PMID- 25591067
TI  - Polymorphs of CaSeO4 under pressure: a first-principles study of structural,
      electronic, and vibrational properties.
AB  - In this paper we report a theoretical study of the CaSeO4 compound at ambient
      pressure and under pressure. Here we made a structural analysis of its three
      known polymorphs--orthorhombic (Cmca), monoclinic monazite, and tetragonal
      scheelite--where direct comparison with experimental measurements is done.
      Besides, the electronic and vibrational structures are reported for the first
      time for those structures. In addition, the behavior of CaSeO4 as a function of
      pressure is studied, where phase transitions are investigated by considering a
      quasiharmonic approximation at 300 K. After a total energy study of 14 possible
      high-pressure phases of CaSeO4, the following sequence of pressure-driven
      structural transitions has been found: orthorhombic (Cmca) -> tetragonal
      scheelite -> monoclinic AgMnO4-type structure. It was observed that monazite is
      less stable as temperature increases, while the opposite occurs for the AgMnO4
      type structure, this being a novel polymorph. This high-pressure structure is a
      distortion of the monazite structure and resembles the distorted barite-type
      structure (P2(1)/n) of CaSO4. The equation of state and the pressure evolution of
      the structural, electronic, and vibrational properties are also reported.

PMID- 25591068
TI  - The Drosophila histone variant H2A.V works in concert with HP1 to promote
      kinetochore-driven microtubule formation.
AB  - Unlike other organisms that have evolved distinct H2A variants for different
      functions, Drosophila melanogaster has just one variant which is capable of
      filling many roles. This protein, H2A.V, combines the features of the conserved
      variants H2A.Z and H2A.X in transcriptional control/heterochromatin assembly and
      DNA damage response, respectively. Here we show that mutations in the gene
      encoding H2A.V affect chromatin compaction and perturb chromosome segregation in
      Drosophila mitotic cells. A microtubule (MT) regrowth assay after cold exposure
      revealed that loss of H2A.V impairs the formation of kinetochore-driven (k)
      fibers, which can account for defects in chromosome segregation. All defects are
      rescued by a transgene encoding H2A.V that lacks the H2A.X function in the DNA
      damage response, suggesting that the H2A.Z (but not H2A.X) functionality of H2A.V
      is required for chromosome segregation. We also found that loss of H2A.V weakens
      HP1 localization, specifically at the pericentric heterochromatin of metaphase
      chromosomes. Interestingly, loss of HP1 yielded not only telomeric fusions but
      also mitotic defects similar to those seen in H2A.V null mutants, suggesting a
      role for HP1 in chromosome segregation. We also show that H2A.V precipitates HP1
      from larval brain extracts indicating that both proteins are part of the same
      complex. Moreover, we found that the overexpression of HP1 rescues chromosome
      missegregation and defects in the kinetochore-driven k-fiber regrowth of H2A.V
      mutants indicating that both phenotypes are influenced by unbalanced levels of
      HP1. Collectively, our results suggest that H2A.V and HP1 work in concert to
      ensure kinetochore-driven MT growth. 

PMID- 25591070
TI  - Metabolism of immune cells.

PMID- 25591069
TI  - Fluorescence-quenching of a liposomal-encapsulated near-infrared fluorophore as a
      tool for in vivo optical imaging.
AB  - Optical imaging offers a wide range of diagnostic modalities and has attracted a
      lot of interest as a tool for biomedical imaging. Despite the enormous number of
      imaging techniques currently available and the progress in instrumentation, there
      is still a need for highly sensitive probes that are suitable for in vivo
      imaging. One typical problem of available preclinical fluorescent probes is their
      rapid clearance in vivo, which reduces their imaging sensitivity. To circumvent
      rapid clearance, increase number of dye molecules at the target site, and thereby
      reduce background autofluorescence, encapsulation of the near-infrared
      fluorescent dye, DY-676-COOH in liposomes and verification of its potential for
      in vivo imaging of inflammation was done. DY-676 is known for its ability to self
      quench at high concentrations. We first determined the concentration suitable for
      self-quenching, and then encapsulated this quenching concentration into the
      aqueous interior of PEGylated liposomes. To substantiate the quenching and
      activation potential of the liposomes we use a harsh freezing method which leads
      to damage of liposomal membranes without affecting the encapsulated dye. The
      liposomes characterized by a high level of fluorescence quenching were termed Lip
      Q. We show by experiments with different cell lines that uptake of Lip-Q is
      predominantly by phagocytosis which in turn enabled the characterization of its
      potential as a tool for in vivo imaging of inflammation in mice models.
      Furthermore, we use a zymosan-induced edema model in mice to substantiate the
      potential of Lip-Q in optical imaging of inflammation in vivo. Considering
      possible uptake due to inflammation-induced enhanced permeability and retention
      (EPR) effect, an always-on liposome formulation with low, non-quenched
      concentration of DY-676-COOH (termed Lip-dQ) and the free DY-676-COOH were
      compared with Lip-Q in animal trials. 

PMID- 25591071
TI  - A case of cerebral phaeohyphomycosis caused by Fonsecaea monophora, a neurotropic
      dematiaceous fungus, and a review of the literature.
AB  - The Fonsecaea species, which are the leading causes of chromoblastomycosis, are
      not considered neurotropic fungal agents. Fonsecaea pedrosoi is the primary
      species in the genus and is usually isolated from chromoblastomycosis cases.
      However, the recently distinguished species F. monophora has been reported in a
      few cerebral phaeohyphomycosis cases. Here, a case of cerebral phaeohyphomycosis
      caused by Fonsecaea monophora is presented in a 71-year-old female subject with
      chronic diabetes mellitus and hypertension. The identification of F. monophora
      was made through mycological and molecular analysis, and an isolate was
      differentiated from the closely related F. pedrosoi by sequence data on key bases
      on the ribosomal internal transcribed spacer region. The case was successfully
      treated with surgical and medical approaches, and the patient has remained
      healthy and stable after a ten-month follow up. Given the increasing incidence of
      this type of infection of the central nervous system (CNS), this case provides
      further support for the consideration that F. monophora might represent a
      neurotropic agent.

PMID- 25591072
TI  - Onychomycosis caused by Onychocola canadensis: the first report in Estonia and
      lessons to learn.
AB  - We report the first case of onychomycosis caused by Onychocola canadensis in
      Estonia. We believe that the number of nail infections caused by this fungus is
      underestimated due to the current diagnostic algorithm of non-dermatophytic
      onychomycosis. The need to define categories and criteria for 'proven' and
      'probable' non-dermatophyte mold infections to promote more extensive studies in
      the future is also discussed. 

PMID- 25591073
TI  - Importance of subcellular metal partitioning and kinetics to predicting sublethal
      effects of copper in two deposit-feeding organisms.
AB  - The role of subcellular partitioning of copper on the sublethal effects to two
      deposit-feeding organisms (41-day growth in the bivalve Tellina deltoidalis and
      11-day reproduction in the amphipod Melita plumulosa) was assessed for copper
      spiked sediments with different geochemical properties. Large differences in
      bioaccumulation and detoxification strategies were observed. The bivalve
      accumulated copper faster than the amphipod, and can be considered a relatively
      strong net bioaccumulator. The bivalve, however, appears to regulate the
      metabolically available fraction (MAF) of the total metal pool by increasing the
      net accumulation rate of copper in the biologically detoxified metal pool (BDM),
      where most of the copper is stored. In the amphipod, BDM concentration remained
      constant with increasing copper exposures and it can be considered a very weak
      net bioaccumulator of copper. This regulation of copper, with relatively little
      stored in detoxified forms, appears to best describe the strategy applied by the
      amphipod to minimize the potential toxic effects of copper. When the EC50 values
      for growth and reproduction are expressed based on the MAF of copper, the
      sensitivity of the two species appears similar, however when expressed based on
      the net accumulation rate of copper in the metabolically available fraction
      (MAFrate), the bivalve appears more sensitive to copper. These results indicate
      that describing the causality of metal effects in terms of kinetics of uptake,
      detoxification, and excretion rather than threshold metal body concentrations is
      more effective in predicting the toxic effects of copper. Although the expression
      of metal toxicity in terms of the rate at which the metal is bioaccumulated into
      metabolically available forms may not be feasible for routine assessments, a
      deeper understanding of uptake rates from all exposure routes may improve our
      ability to assess the risk posed by metal-contaminated sediments.

PMID- 25591074
TI  - 99mTc-labeled single-domain antibody EG2 in targeting epidermal growth factor
      receptor: an in-vitro and mouse model in-vivo study.
AB  - OBJECTIVE: The aim of this study was to explore the targeting ability and
      metabolic characteristics of the technetium-99m-labeled single-domain antibody
      (99mTc-sdAb) EG2 targeting epidermal growth factor receptor (EGFR) through an in
      vitro and in-vivo study. MATERIALS AND METHODS: The sdAb EG2 was radiolabeled
      with Tc using a tricarbonyl kit. The EGFR expression level of A431 and OCM-1
      cells was confirmed using immunofluorescence staining. Cell binding, blocking,
      uptake, and efflux studies were performed to investigate the binding specificity
      of 99mTc-sdAb EG2 in vitro. Single-photon emission computed tomography imaging
      and biodistribution studies were used to explore the targeting abilities and
      metabolic characteristics of Tc-sdAb EG2 in vivo. RESULTS: 99mTc-sdAb EG2 was
      successfully prepared with labeling yields of 60-71% and specific activity of
      1.83+/-0.29 GBq/mg (n=3). Immunofluorescence staining revealed high and low EGFR
      expression on the surface of A431 and OCM-1 cells, respectively. The binding
      affinity of 99mTc-sdAb EG2 to A431 cells was 43.53+/-1.89 nmol/l. 99mTc-sdAb EG2
      uptake in A431 cells in vitro could be blocked by ~19, 40, and 66% in the
      presence of excess unlabeled sdAb EG2 at 100, 500, and 1000 nmol/l, respectively.
      Single-photon emission computed imaging indicated that A431 tumor images could be
      clearly displayed at early scan time points after 99mTc-sdAb EG2 injection, even
      as early as 1 h. Biodistribution study showed that the A431 tumor uptake of 99mTc
      sdAb EG2 was blocked by about 51% at 3 h after coinjecting excess of sdAb EG2.
      However, there were almost no OCM-1 tumor images at the corresponding scan time
      points and the OCM-1 tumor uptake was only 0.40+/-0.13% injected dose per gram of
      tissue (n=5) at 3 h. CONCLUSION: This study demonstrated that sdAb EG2 can
      effectively target EGFR in vitro and in vivo in tumors, suggesting that it could
      be used as a molecular probe for EGFR detection.

PMID- 25591075
TI  - Simple method for fluorescence DNA in situ hybridization to squashed chromosomes.
AB  - DNA in situ hybridization (DNA ISH) is a commonly used method for mapping
      sequences to specific chromosome regions. This approach is particularly effective
      at mapping highly repetitive sequences to heterochromatic regions, where
      computational approaches face prohibitive challenges. Here we describe a
      streamlined protocol for DNA ISH that circumvents formamide washes that are
      standard steps in other DNA ISH protocols. Our protocol is optimized for
      hybridization with short single strand DNA probes that carry fluorescent dyes,
      which effectively mark repetitive DNA sequences within heterochromatic
      chromosomal regions across a number of different insect tissue types. However,
      applications may be extended to use with larger probes and visualization of
      single copy (non-repetitive) DNA sequences. We demonstrate this method by mapping
      several different repetitive sequences to squashed chromosomes from Drosophila
      melanogaster neural cells and Nasonia vitripennis spermatocytes. We show
      hybridization patterns for both small, commercially synthesized probes and for a
      larger probe for comparison. This procedure uses simple laboratory supplies and
      reagents, and is ideal for investigators who have little experience with
      performing DNA ISH. 

PMID- 25591076
TI  - SNP discovery and genotyping using restriction-site-associated DNA sequencing in
      chickens.
AB  - Single nucleotide polymorphisms (SNPs) are essential to the understanding of
      population genetic variation and diversity. Here, we performed restriction-site
      associated DNA sequencing (RAD-seq) on 72 individuals from 13 Chinese indigenous
      and three introduced chicken breeds. A total of 620 million reads were obtained
      using an Illumina Hiseq2000 sequencer. An average of 75,587 SNPs were identified
      from each individual. Further filtering strictly validated 28,895 SNPs candidates
      for all populations. When compared with the NCBI dbSNP (chicken_9031), 15,404
      SNPs were new discoveries. In this study, RAD-seq was performed for the first
      time on chickens, implicating the remarkable effectiveness and potential
      applications on genetic analysis and breeding technique for whole-genome
      selection in chicken and other agricultural animals.

PMID- 25591077
TI  - Phosphopeptide analysis of rodent epididymal spermatozoa.
AB  - Spermatozoa are quite unique amongst cell types. Although produced in the testis,
      both nuclear gene transcription and translation are switched off once the pre
      cursor round cell begins to elongate and differentiate into what is
      morphologically recognized as a spermatozoon. However, the spermatozoon is very
      immature, having no ability for motility or egg recognition. Both of these events
      occur once the spermatozoa transit a secondary organ known as the epididymis.
      During the ~12 day passage that it takes for a sperm cell to pass through the
      epididymis, post-translational modifications of existing proteins play a pivotal
      role in the maturation of the cell. One major facet of such is protein
      phosphorylation. In order to characterize phosphorylation events taking place
      during sperm maturation, both pure sperm cell populations and pre-fractionation
      of phosphopeptides must be established. Using back flushing techniques, a method
      for the isolation of pure spermatozoa of high quality and yield from the distal
      or caudal epididymides is outlined. The steps for solubilization, digestion, and
      pre-fractionation of sperm phosphopeptides through TiO2 affinity chromatography
      are explained. Once isolated, phosphopeptides can be injected into MS to identify
      both protein phosphorylation events on specific amino acid residues and quantify
      the levels of phosphorylation taking place during the sperm maturation processes.

PMID- 25591078
TI  - Fast and cost-effective fabrication of large-area plasmonic transparent biosensor
      array.
AB  - Surface enhanced Raman-based sensors are widely used for chemical and biological
      species analysis; but to date the high cost, long production time, hazardous, and
      toxic content as well as small sensing area and opacity are limiting their
      capabilities for widespread applications in the medical and environmental fields.
      We present a novel cost-effective method for fast laser-based fabrication of
      affordable large-area and transparent periodic arrays of ligand-free metallic
      nanoparticles, offering a maximum possibility for the adsorption/immobilization
      of molecules and labeling. Further, we demonstrate a remarkable detection limit
      in the picomolar range by means of Raman scattering, thus evidencing a superior
      signal-to-noise ratio compared to other sensor substrates. The high sensitivity
      performance along with a fast and cheap fabrication procedure of reusable large
      area transparent plasmonic devices opens the route for direct, in situ multimodal
      optical analysis with broad applications in the biomedical/analytical fields. 

PMID- 25591080
TI  - Explicit and implicit components of visuo-motor adaptation: An analysis of
      individual differences.
AB  - Adaptation to visuo-motor rotations embraces implicit and explicit components. We
      contrast this two-component model with a three-component model by means of an
      individual-differences approach. Adaptive changes were tested under four
      conditions: (1) closed-loop test, presence of the rotation cued (initial adaptive
      shift), (2) open-loop test, presence of the rotation cued (adaptive shift), (3)
      open-loop test, absence of the rotation cued (after-effect), (4) test of explicit
      knowledge (explicit shift). After-effects and explicit shifts were uncorrelated.
      After regression on after-effects and explicit shifts, the residuals of the
      initial adaptive shifts and the adaptive shifts remained correlated, suggesting
      an additional implicit component of adaptation found only in the cued presence of
      the visuo-motor rotation. The two implicit components are consistent with the
      distinction between a change of the body schema giving rise to after-effects, and
      the development of an internal model of a tool that is applied only when the
      transformation is present. 

PMID- 25591079
TI  - Normal and malignant muscle cell transplantation into immune compromised adult
      zebrafish.
AB  - Zebrafish have become a powerful tool for assessing development, regeneration,
      and cancer. More recently, allograft cell transplantation protocols have been
      developed that permit engraftment of normal and malignant cells into irradiated,
      syngeneic, and immune compromised adult zebrafish. These models when coupled with
      optimized cell transplantation protocols allow for the rapid assessment of stem
      cell function, regeneration following injury, and cancer. Here, we present a
      method for cell transplantation of zebrafish adult skeletal muscle and embryonal
      rhabdomyosarcoma (ERMS), a pediatric sarcoma that shares features with embryonic
      muscle, into immune compromised adult rag2(E450fs) homozygous mutant zebrafish.
      Importantly, these animals lack T cells and have reduced B cell function,
      facilitating engraftment of a wide range of tissues from unrelated donor animals.
      Our optimized protocols show that fluorescently labeled muscle cell preparations
      from alpha-actin-RFP transgenic zebrafish engraft robustly when implanted into
      the dorsal musculature of rag2 homozygous mutant fish. We also demonstrate
      engraftment of fluorescent-transgenic ERMS where fluorescence is confined to
      cells based on differentiation status. Specifically, ERMS were created in AB
      strain myf5-GFP; mylpfa-mCherry double transgenic animals and tumors injected
      into the peritoneum of adult immune compromised fish. The utility of these
      protocols extends to engraftment of a wide range of normal and malignant donor
      cells that can be implanted into dorsal musculature or peritoneum of adult
      zebrafish. 

PMID- 25591081
TI  - FIM imaging and FIMtrack: two new tools allowing high-throughput and cost
      effective locomotion analysis.
AB  - The analysis of neuronal network function requires a reliable measurement of
      behavioral traits. Since the behavior of freely moving animals is variable to a
      certain degree, many animals have to be analyzed, to obtain statistically
      significant data. This in turn requires a computer assisted automated
      quantification of locomotion patterns. To obtain high contrast images of almost
      translucent and small moving objects, a novel imaging technique based on
      frustrated total internal reflection called FIM was developed. In this setup,
      animals are only illuminated with infrared light at the very specific position of
      contact with the underlying crawling surface. This methodology results in very
      high contrast images. Subsequently, these high contrast images are processed
      using established contour tracking algorithms. Based on this, we developed the
      FIMTrack software, which serves to extract a number of features needed to
      quantitatively describe a large variety of locomotion characteristics. During the
      development of this software package, we focused our efforts on an open source
      architecture allowing the easy addition of further modules. The program operates
      platform independent and is accompanied by an intuitive GUI guiding the user
      through data analysis. All locomotion parameter values are given in form of csv
      files allowing further data analyses. In addition, a Results Viewer integrated
      into the tracking software provides the opportunity to interactively review and
      adjust the output, as might be needed during stimulus integration. The power of
      FIM and FIMTrack is demonstrated by studying the locomotion of Drosophila larvae.

PMID- 25591082
TI  - Strategy for universal access to health and universal health coverage and the
      contribution of the International Nursing Networks.

PMID- 25591084
TI  - Medication adherence and quality of life among the elderly with diabetic
      retinopathy.
AB  - METHOD: one hundred (n=100) elderly outpatients with diabetic retinopathy taking
      antihypertensives and/or oral antidiabetics/insulin were interviewed. Adherence
      was evaluated by the adherence proportion and its association with the care taken
      in administrating medications and by the Morisky Scale. The National Eye
      Institute Visual Functioning Questionnaire (NEI VFQ-25) was used to evaluate
      HRQoL. RESULTS: most (58%) reported the use of 80% or more of the prescribed dose
      and care in utilizing the medication. The item "stopping the drug when
      experiencing an adverse event", from the Morisky Scale, explained 12.8% and 13.5%
      of the variability of adherence proportion to antihypertensives and oral
      antidiabetics/insulin, respectively. CONCLUSION: there was better HRQoL in the
      Color Vision, Driving and Social Functioning domains of the NEI VFQ-25.
      Individuals with lower scores on the NEI VFQ-25 and higher scores on the Morisky
      Scale presented greater chance to be nonadherent to the pharmacological treatment
      of diabetes and hypertension.

PMID- 25591083
TI  - Evaluation of perineal muscle strength in the first trimester of pregnancy.
AB  - OBJECTIVES: to analyze the Pelvic Floor Muscle Strength (PFMS) of pregnant women
      with one or more vaginal or cesarean deliveries; to compare the PFMS of these
      with pregnant women with the PFMS of primiparous women. METHODS: cross-sectional
      study with women up to 12 weeks pregnant, performed in Itapecerica da Serra, Sao
      Paulo state, from December 2012 to May 2013. The sample consisted of 110 pregnant
      women with one or more vaginal deliveries or cesarean sections and 110
      primigravidae. The PFMS was evaluated by perineometry (Peritron(tm)) and vaginal
      digital palpation (modified Oxford scale). RESULTS: the average PFMS in pregnant
      women with a history of vaginal delivery or cesarean section was 33.4 (SD=21.2)
      cmH2O. From the Oxford scale, 75.4% of the pregnant women with previous vaginal
      or cesarean deliveries presented grade <= 2, and 5.5% grade >= 4; among the
      primiparae, 39.9% presented grade <= 2, and 50.9% grade >= 4, with a
      statistically significant difference (p<0.001). From the perineometry, there was
      no statistically significant difference between the PFMS and age, type of
      delivery, parity, body mass index, and genitourinary tract symptoms, however,
      there was a statistically significant difference between the pregnant women with
      and without a history of episiotomy (p=0.04). In the palpation, none of the
      variables showed a statistically significant difference. CONCLUSION: pregnancy
      and childbirth can reduce the PFMS.

PMID- 25591085
TI  - Quality of life/spirituality, religion and personal beliefs of adult and elderly
      chronic kidney patients under hemodialysis.
AB  - OBJECTIVE: to assess the quality of life of chronic kidney patients undergoing
      hemodialysis, using the WHOQOL-bref and WHOQOL-SRPB. METHOD: a descriptive and
      cross-sectional study was undertaken at a kidney replacement therapy service in
      the interior of the state of SP. The 110 subjects who complied with the inclusion
      criteria answered the Subject Characterization Instrument, the WHOQOL-bref and
      WHOQOL-SRPB. RESULTS: most of the respondents were male (67.27%), with a mean age
      of 55.65 years, Catholic (55.45%), with unfinished primary education (33.64%) and
      without formal occupation (79.08%). The WHOQOL-bref domains with the highest and
      lowest mean score were, respectively, "psychological" (u=74.20) and "physical"
      (u=61.14). The WHOQOL-SRPB domains with the highest and lowest mean score were,
      respectively, "completeness and integration" (u=4.00) and "faith" (u=4.40).
      CONCLUSIONS: the respondents showed high quality of life scores, specifically in
      the dimensions related to spirituality, religion and personal beliefs. Losses
      were evidenced in the physical domain of quality of life, possibly due to the
      changes resulting from the chronic kidney disease and hemodialysis treatment.

PMID- 25591086
TI  - The health-disease process and the family health strategy: the user's
      perspective.
AB  - OBJECTIVE: to analyze the meanings Primary Health Care users attribute to their
      health-disease process and the services used. METHODS: this qualitative research
      uses the focus group technique to interview two groups of users the service
      monitors. The first is a group of elderly people and the second of pregnant
      women. To analyze the meanings, the discourse analysis technique and the
      reference framework of health promotion are used. RESULTS: the group of elderly,
      being mostly female arterial hypertension and diabetes mellitus patients,
      visualizes the health-disease process as the evolution of human existence
      controlled by divine power, signifying the health service as a blessing in the
      control of the disease. The Group of young pregnant women signified health as the
      ability for self-care and disease as the disability for that purposes,
      considering the Primary Health Care service as responsible for the recovery of
      individual and family health. FINAL CONSIDERATIONS: the users demonstrated
      dissatisfaction with bureaucratic and vertical relations present at the health
      services. In each group, it was observed that the meanings for health and disease
      and meanings of the health service the users elaborated can be related.

PMID- 25591087
TI  - Burnout syndrome among undergraduate nursing students at a public university.
AB  - OBJECTIVE: to investigate the burnout syndrome and its relationship with
      demographic and academic variables among undergraduate nursing students at a
      public university in Southern Brazil. METHOD: a quantitative study with 168
      students, by applying an adaptation of the Maslach Burnout Inventory - Student
      Survey, validated for this study. We used descriptive and variance analysis of
      the data analysis. RESULTS: we found that students do not have the burnout
      syndrome, manifesting high average scores in Emotional Exhaustion, low in
      Disbelief and high in Professional Effectiveness; that younger students who
      perform leisure activities have greater Professional Effectiveness, unlike
      students in early grades with no extracurricular activities; combining work and
      studies negatively influenced only the Professional Effectiveness factor, while
      the intention of giving up influenced negatively Disbelief and Professional
      Effectiveness factors. CONCLUSION: the situations that lead students to Emotional
      Exhaustion need to be recognized, considering the specificity of their study
      environments.

PMID- 25591088
TI  - Applying Nightingale charts to evaluate the heterogeneity of biomedical waste in
      a Hospital.
AB  - OBJECTIVES: to evaluate the heterogeneity of biomedical waste (BW) using
      Nightingale charts. METHOD: cross-sectional study consisting of data collection
      on wastes (direct observation of receptacles, physical characterisation, and
      gravimetric composition), development of a Management Information System, and
      creation of statistical charts. RESULTS: the wastes with the greatest degree of
      heterogeneity are, in order, recyclable, infectious, and organic wastes; chemical
      waste had the most efficient segregation; Nightingale charts are useful for quick
      visualisation and systematisation of information on heterogeneity. CONCLUSION:
      the development of a management information system and the use of Nightingale
      charts allows for the identification and correction of errors in waste
      segregation, which increase health risks and contamination by infectious and
      chemical wastes and reduce the sale and profit from recyclables.

PMID- 25591089
TI  - Factors associated with satisfaction at work in Psychosocial Care Centers.
AB  - OBJECTIVES: to analyze the prevalence of satisfaction at work and identify
      associated factors in Psychosocial Care Centers. METHOD: cross-sectional study
      involving 546 workers from 40 Psychosocial Care Centers in the South of Brazil.
      The satisfaction was identified based on the Assessment Scale of Satisfaction in
      the Mental Health Team and a logistic regression model was used for the adjusted
      data analysis. RESULTS: the prevalence of satisfaction at work corresponded to
      66.4%. Factors directly associated with satisfaction: higher-level function
      (except physicians and psychologists), work time of six months or less, making a
      larger number of home visits, good supervision by the team, possibility to make
      collective choices and take courses. CONCLUSIONS: the satisfaction is associated
      with the work organization and conditions and demonstrates the need to invest in
      team supervisions, in process that democratize the services and in the workers'
      training.

PMID- 25591090
TI  - Nurses' workload and its relation with physiological stress reactions.
AB  - OBJECTIVE: to analyze the relation between the workload and the physiological
      stress reactions among nurses working at a hospital service. METHODS: cross
      sectional, correlational, quantitative study, involving 95 nurses, in 2011 and
      2012. Spearman's bivariate Correlation Test was used. RESULTS: most subjects are
      female, between 23 and 61 years old and working between 21 and 78 hours per week.
      The most frequent physiological reactions were back pain, fatigue/exhaustion,
      stiff neck and stomach acidity, with 46.3% of the subjects presenting low and
      42.1% moderate physiological stress responses. No correlation was found between
      the workload and the physiological stress responses. CONCLUSION: although most of
      the nurses work more than 36 hours/week, physiologically, they do not present
      high reaction levels in response to stress. These workers deal with conflicts in
      the vertical and horizontal relations between professionals, family members and
      patients. In that sense, taking care of professionals who offer health services
      can be a fundamental strategy, as good user care mainly depends on healthy teams.

PMID- 25591091
TI  - The adaptation problems of patients undergoing hemodialysis: socio-economic and
      clinical aspects.
AB  - OBJECTIVES: to identify adaptation problems under Roy's Model in patients
      undergoing hemodialysis and to correlate them with the socioeconomic and clinical
      aspects. METHOD: a transversal study, undertaken using a questionnaire. The
      sample was made up of 178 individuals. The Chi-squared and Mann-Whitney U tests
      were undertaken. RESULTS: the adaptation problems and the socioeconomic and
      clinical aspects which presented statistical associations were: Hyperkalemia and
      age; Edema and income; Impairment of a primary sense: touch and income; Role
      failure and age; Sexual dysfunction and marital status and sex; Impairment of a
      primary sense: vision and years of education; Intolerance to activity and years
      of education; Chronic pain and sex and years of education; Impaired skin
      integrity and age: Hypocalcemia and access; Potential for injury and age and
      years of education; Nutrition below the organism's requirements and age;
      Impairment of a primary sense: hearing and sex and kinetic evaluation of urea;
      Mobility in gait and/or coordination restricted, and months of hemodialysis; and,
      Loss of ability for self-care, and months of hemodialysis and months of illness.
      CONCLUSION: adaptation problems in the clientele undergoing hemodialysis can be
      influenced by socioeconomic/clinical data. These findings contribute to the
      development of the profession, fostering the nurse's reflection regarding the
      care.

PMID- 25591092
TI  - Neck circumference as a potential marker of metabolic syndrome among college
      students.
AB  - OBJECTIVE: to relate neck circumference with metabolic syndrome and its criteria
      among college students. METHOD: cross-sectional study conducted with 702 college
      students in Fortaleza, CE, Brazil from September 2010 to June 2011. Socio
      demographic data, waist circumference and neck circumference were collected
      together with blood pressure, fasting blood sugar, triglyceride levels, and HDL
      C. RESULTS: 1.7% of the studied sample presented metabolic syndrome. Of these,
      58.3% presented altered neck circumference (p<0.006). As neck circumference
      decreases, pressure levels improve (p<0.001). Additionally, college students with
      high fasting blood sugar (p=0.003) and high triglyceride levels (p<0.001)
      presented higher values of neck circumference. CONCLUSION: neck circumference is
      a potential predictive marker in the detection of metabolic syndrome and its
      components among college students.

PMID- 25591093
TI  - "The group facilitates everything": meanings patients with type 2 diabetes
      mellitus assigned to health education groups.
AB  - OBJECTIVE: to interpret the meanings patients with type 2 diabetes mellitus
      assign to health education groups. METHOD: ethnographic study conducted with
      Hyperdia groups of a healthcare unit with 26 informants, with type 2 diabetes
      mellitus, and having participated in the groups for at least three years.
      Participant observation, social characterization, discussion groups and semi
      structured interviews were used to collect data. Data were analyzed through the
      thematic coding technique. RESULTS: four thematic categories emerged: ease of
      access to the service and healthcare workers; guidance on diabetes; participation
      in groups and the experience of diabetes; and sharing knowledge and experiences.
      The most relevant aspect of this study is the social use the informants in
      relation to the Hyperdia groups under study. CONCLUSION: the studied groups are
      agents producing senses and meanings concerning the process of becoming ill and
      the means of social navigation within the official health system. We expect this
      study to contribute to the actions of healthcare workers coordinating these
      groups given the observation of the cultural universe of these individuals
      seeking professional care in the various public health care services.

PMID- 25591094
TI  - Discomfort and unease of the subject in the interpretation movement of a
      Tuberculosis questionnaire.
AB  - OBJECTIVE: to propose a discussion about traces of the derivation of meanings,
      the subjects' discomfort and resistance when they are called upon to signify a
      questionnaire on the transfer of the Directly Observed Treatment of Tuberculosis
      policy, in order to reveal the limitations of closed questionnaires in the
      subject's interpretation process. METHOD: health professionals from a Primary
      Health Care Unit in Porto Alegre/RS were interviewed and some excerpts from the
      interviews were investigated in the light of French Discourse Analysis. RESULTS:
      resistance, discomfort, slips, silencing and the derivation of meanings were
      observed in the subjects' interpretation. CONCLUSION: the interpretation process
      has multiple meanings and varies from subject to subject. The questionnaire, as a
      prototype of the logically stabilized universe, fails when the purpose is to
      control the interpretation. Its isolated use in health research can entail
      inexactness or incompleteness of the collected data. Therefore, its use
      associated with qualitative research techniques is ideal.

PMID- 25591096
TI  - Adaptation and validation of the Inventory of Family Protective Factors for the
      Portuguese culture.
AB  - OBJECTIVES: to adapt and validate the Inventory of Family Protective Factors
      (IFPF) for the Portuguese culture. This instrument assesses protective factors
      that contribute to family resilience. Studies addressing resilience are embedded
      within the salutogenic paradigm, i.e. it addresses protective factors of
      individuals or groups without underestimating risk factors or vulnerability.
      METHOD: in order to assess the IFPF's linguistic and conceptual equivalence, the
      instrument was translated, retro-translated and the think-aloud protocol was
      used. We then verified the instrument's sensitiveness, reliability and validity
      of results to assess its psychometric characteristics. A factor analysis was
      performed of the principal components with varimax rotation of the scale's items
      and Cronbach's alpha coefficient was calculated for each dimension. A total of 85
      families with disabled children, selected through simple random sampling, self
      administered the instrument. RESULTS: the IFPF presents psychometric
      characteristics that are appropriate for the Portuguese population (Cronbach's
      alpha = .90). CONCLUSION: the IFPF was adapted and validated for the Portuguese
      culture and is an instrument to be used in studies intended to assess protective
      factors of family resilience.

PMID- 25591095
TI  - Quality of life, clinical characteristics and treatment adherence of people
      living with HIV/AIDS.
AB  - OBJECTIVES: to assess the quality of life of people living with HIV/AIDS and
      verify its association with clinical characteristics and treatment adherence.
      METHOD: cross-sectional study conducted in a hospital in the state of Paraiba,
      Brazil. A questionnaire was used to collect socio-demographic and clinical data.
      The quality of life scale proposed by the World Health Organization and a
      questionnaire to measure treatment adherence were used. RESULTS: of the 314
      interviewees, 190 (60.5%) were male, aged 43 years on average, 121 (38.5%) had
      attended up to five years of schooling, 108 (34.4%) received up to two times the
      minimum wage, and 112 (35.7%) were on sick leave. In regard to clinical
      variables, individuals with an undetectable viral load scored higher in all the
      domains concerning quality of life, with statistically significant differences in
      three domains. Regarding treatment adherence, 235 (73.8%) presented poor
      adherence and those who strictly adhered to treatment obtained better scores in
      quality of life. The results show that quality of life is better among
      individuals adherent to ART. Supporting people to adhere to the antiretroviral
      treatment should be a persistent task of healthcare workers and other people
      participating in the treatment, such as family members and friends.

PMID- 25591097
TI  - Sociodemographic and health factors associated with chronic pain in
      institutionalized elderly.
AB  - OBJECTIVES: to characterize chronic pain in institutionalized elderly and verify
      the associated factors. METHOD: observational, cross-sectional and non
      experimental study with a quantitative approach. The study participants were 124
      elderly living in Long-Term Care Institutions for the Elderly (LTCIs) in a city
      in Minas Gerais (Brazil). Approval for the project was obtained from the Research
      Ethics Committee. The elderly's clinical and sociodemographic variables and pain
      related aspects were assessed. The data were analyzed through descriptive
      statistics and bivariate analysis (chi-squared). RESULTS: the prevalence of
      chronic pain corresponded to 58.1%; for more than 10 years (26.4%); in lower
      limbs (31.9%); characterized as "twinges" (33.3%); 33.3% adopted medication
      treatment; the pain did not improve (41.7 %); or worsen (34.7 %). It was
      evidenced that elderly aged 60? 70 old had 70% less chances of chronic pain than
      those aged 80 years and older (p=0.018). CONCLUSION: institutionalized elderly
      have a high prevalence of chronic pain, mainly in the lower limbs. No factors of
      pain improvement or worsening were identified and medication was evidenced as the
      preferred treatment. Age showed to be associated with the presence of pain. It is
      considered important to accomplish multiprofessional actions at the LTCIs to
      guide prevention and rehabilitation actions of the pain episodes in these
      elderly.

PMID- 25591098
TI  - Deaths from homicides: a historical series.
AB  - OBJECTIVE: to describe mortality from homicides in Itabuna, in the State of
      Bahia. METHOD: study with hybrid, ecological and time-trend design. The mortality
      coefficients per 1,000 inhabitants, adjusted by the direct technique,
      proportional mortality by sex and age range, and Potential Years of Life Lost
      were all calculated. RESULTS: since 2005, the external causes have moved from
      third to second most-common cause of death, with homicides being responsible for
      the increase. In the 13 years analyzed, homicides have risen 203%, with 94% of
      these deaths occurring among the male population. Within this group, the growth
      occurred mainly in the age range from 15 to 29 years of age. It was ascertained
      that 83% of the deaths were caused by firearms; 57.2% occurred in public
      thoroughfares; and 98.4% in the urban zone. In 2012, the 173 homicides resulted
      in 7,837 potential years of life lost, with each death causing, on average, the
      loss of 45.3 years. CONCLUSIONS: mortality by homicide in a medium-sized city in
      Bahia reaches levels observed in the big cities of Brazil in the 1980s,
      evidencing that the phenomenon of criminality - formerly predominant only in the
      big urban centers - is advancing into the rural area of Brazil, causing changes
      in the map of violent homicide in Brazil.

PMID- 25591099
TI  - The Idealized Brazilian Health System versus the real one: contributions from the
      nursing field.
AB  - OBJECTIVE: to identify the perceptions of professionals working in a facility
      connected with the Brazilian Unified Health System - SUS in regard to what they
      know, think and talk about public health policy. METHOD: this exploratory
      descriptive study with a qualitative nature was conducted with 28 professionals
      working in a facility connected with the SUS. Data were collected through
      interviews with guiding questions and analyzed through the thematic content
      analysis technique. RESULTS: coded and interpreted data resulted in three
      thematic axes: The SUS - perfect web that does not work in practice; The
      recurrent habit of complaining about the SUS; The need to rethink the way of
      thinking about, acting in and managing the SUS. CONCLUSION: the professionals
      working for the SUS are aware of the principles and guidelines that govern the
      Brazilian health system, however, they reproduce a dichotomous and linear model
      of conception and practice strongly linked to the thinking of society in general.

PMID- 25591100
TI  - Clinical Alarms in intensive care: implications of alarm fatigue for the safety
      of patients.
AB  - OBJECTIVES: to identify the number of electro-medical pieces of equipment in a
      coronary care unit, characterize their types, and analyze implications for the
      safety of patients from the perspective of alarm fatigue. METHOD: this
      quantitative, observational, descriptive, non-participatory study was conducted
      in a coronary care unit of a cardiology hospital with 170 beds. RESULTS: a total
      of 426 alarms were recorded in 40 hours of observation: 227 were triggered by
      multi-parametric monitors and 199 were triggered by other equipment (infusion
      pumps, dialysis pumps, mechanical ventilators, and intra-aortic balloons); that
      is an average of 10.6 alarms per hour. CONCLUSION: the results reinforce the
      importance of properly configuring physiological variables, the volume and
      parameters of alarms of multi-parametric monitors within the routine of intensive
      care units. The alarms of equipment intended to protect patients have increased
      noise within the unit, the level of distraction and interruptions in the
      workflow, leading to a false sense of security.

PMID- 25591101
TI  - Prevalence of metabolic components in university students.
AB  - OBJECTIVE: to identify the frequency of components of Metabolic Syndrome (MetS)
      among university students. METHOD: descriptive study with 550 students, from
      various courses run by a public university. The socioeconomic data, lifestyle,
      and components of MetS were filled out using a questionnaire. Blood sample
      collection was undertaken in the university itself by a contracted clinical
      analysis laboratory. RESULTS: 66.2% were female, with a mean age of 22.6+/-4.41;
      71.7% were sedentary; 1.8% stated that they smoke; and 48.5% were classified as
      at medium risk for alcoholism. 5.8% had raised abdominal circumference and 20.4%
      had excess weight; 1.3% and 18.9% had raised fasting blood glucose levels and
      triglycerides, respectively; 64.5% had low HDL cholesterol and 8.7% had blood
      pressure levels compatible with borderline high blood pressure. Thus, of the
      sample, 64.4% had at least one component for MetS; 11.6% had two, and 3.5% had
      three or more. CONCLUSION: a significant proportion of the population already has
      the components for metabolic syndrome, and this profile reinforces the importance
      of early diagnosis so as to reduce the risk of developing chronic comorbidities.

PMID- 25591102
TI  - Factors associated with reporting of abuse against children and adolescents by
      nurses within Primary Health Care.
AB  - OBJECTIVE: to analyze the factors associated with the underreporting on the part
      of nurses within Primary Health Care of abuse against children and adolescents.
      METHOD: cross-sectional study with 616 nurses. A questionnaire addressed socio
      demographic data, profession, instrumentation and knowledge on the topic,
      identification and reporting of abuse cases. Bivariate and multivariate logistic
      regression was used. RESULTS: female nurses, aged between 21 and 32 years old,
      not married, with five or more years since graduation, with graduate studies, and
      working for five or more years in PHC predominated. The final regression model
      showed that factors such as working for five or more years, having a reporting
      form within the PHC unit, and believing that reporting within Primary Health Care
      is an advantage, facilitate reporting. CONCLUSION: the study's results may, in
      addition to sensitizing nurses, support management professionals in establishing
      strategies intended to produce compliance with reporting as a legal device that
      ensures the rights of children and adolescents.

PMID- 25591104
TI  - Robust Ultraviolet-Visible (UV-Vis) Partial Least-Squares (PLS) Models for Tannin
      Quantification in Red Wine.
AB  - The validation of ultraviolet-visible (UV-vis) spectroscopy combined with partial
      least-squares (PLS) regression to quantify red wine tannins is reported. The
      methylcellulose precipitable (MCP) tannin assay and the bovine serum albumin
      (BSA) tannin assay were used as reference methods. To take the high variability
      of wine tannins into account when the calibration models were built, a diverse
      data set was collected from samples of South African red wines that consisted of
      18 different cultivars, from regions spanning the wine grape-growing areas of
      South Africa with their various sites, climates, and soils, ranging in vintage
      from 2000 to 2012. A total of 240 wine samples were analyzed, and these were
      divided into a calibration set (n = 120) and a validation set (n = 120) to
      evaluate the predictive ability of the models. To test the robustness of the PLS
      calibration models, the predictive ability of the classifying variables cultivar,
      vintage year, and experimental versus commercial wines was also tested. In
      general, the statistics obtained when BSA was used as a reference method were
      slightly better than those obtained with MCP. Despite this, the MCP tannin assay
      should also be considered as a valid reference method for developing PLS
      calibrations. The best calibration statistics for the prediction of new samples
      were coefficient of correlation (R2val) = 0.89, root mean standard error of
      prediction (RMSEP) = 0.16, and residual predictive deviation (RPD) = 3.49 for MCP
      and R2val = 0.93, RMSEP = 0.08, and RPD = 4.07 for BSA, when only the UV region
      (260-310 nm) was selected, which also led to a faster analysis time. In addition,
      a difference in the results obtained when the predictive ability of the
      classifying variables vintage, cultivar, or commercial versus experimental wines
      was studied suggests that tannin composition is highly affected by many factors.
      This study also discusses the correlations in tannin values between the
      methylcellulose and protein precipitation methods.

PMID- 25591103
TI  - Predictive factors of alcohol and tobacco use in adolescents.
AB  - OBJECTIVES: to analyze the effect of self-esteem, assertiveness, self-efficacy
      and resiliency on alcohol and tobacco consumption in adolescents. METHOD: a
      descriptive and correlational study was undertaken with 575 adolescents in 2010.
      The Self-Esteem Scale, the Situational Confidence Scale, the Assertiveness
      Questionnaire and the Resiliency Scale were used. RESULTS: the adjustment of the
      logistic regression model, considering age, sex, self-esteem, assertiveness, self
      efficacy and resiliency, demonstrates significance in the consumption of alcohol
      and tobacco. Age, resiliency and assertiveness predict alcohol consumption in the
      lifetime and assertiveness predicts alcohol consumption in the last year.
      Similarly, age and sex predict tobacco consumption in the lifetime and age in the
      last year. CONCLUSION: this study can offer important information to plan nursing
      interventions involving adolescent alcohol and tobacco users.

PMID- 25591106
TI  - Depth-sensitive subsurface imaging of polymer nanocomposites using second
      harmonic Kelvin probe force microscopy.
AB  - We study the depth sensitivity and spatial resolution of subsurface imaging of
      polymer nanocomposites using second harmonic mapping in Kelvin Probe Force
      Microscopy (KPFM). This method allows the visualization of the clustering and
      percolation of buried Single Walled Carbon Nanotubes (SWCNTs) via capacitance
      gradient (?C/?z) maps. We develop a multilayered sample where thin layers of neat
      Polyimide (PI) (~80 nm per layer) are sequentially spin-coated on well-dispersed
      SWCNT/Polyimide (PI) nanocomposite films. The multilayer nanocomposite system
      allows the acquisition of ?C/?z images of three-dimensional percolating networks
      of SWCNTs at different depths in the same region of the sample. We detect CNTs at
      a depth of ~430 nm, and notice that the spatial resolution progressively
      deteriorates with increasing depth of the buried CNTs. Computational trends of
      ?C/?z vs CNT depth correlate the sensitivity and depth resolution with field
      penetration and spreading, and enable a possible approach to three-dimensional
      subsurface structure reconstruction. The results open the door to nondestructive,
      three-dimensional tomography and nanometrology techniques for nanocomposite
      applications. 

PMID- 25591107
TI  - Reemerging Ebola haemorrhagic fever 2014 and the risks of its introduction into
      Brazil.

PMID- 25591105
TI  - Poultry farms as a source of avian influenza A (H7N9) virus reassortment and
      human infection.
AB  - Live poultry markets are a source of human infection with avian influenza A
      (H7N9) virus. On February 21, 2014, a poultry farmer infected with H7N9 virus was
      identified in Jilin, China, and H7N9 and H9N2 viruses were isolated from the
      patient's farm. Reassortment between these subtype viruses generated five
      genotypes, one of which caused the human infection. The date of H7N9 virus
      introduction to the farm is estimated to be between August 21, 2013 (95%
      confidence interval [CI] June 6, 2013-October 6, 2013) and September 25, 2013
      (95% CI May 28, 2013-January 4, 2014), suggesting that the most likely source of
      virus introduction was the first batch of poultry purchased in August 2013. The
      reassortment event that led to the human virus may have occurred between January
      2, 2014 (95% CI November 8, 2013-February 12, 2014) and February 12, 2014 (95% CI
      January 19, 2014-February 18, 2014). Our findings demonstrate that poultry farms
      could be a source of reassortment between H7N9 virus and H9N2 virus as well as
      human infection, which emphasizes the importance to public health of active avian
      influenza surveillance at poultry farms. 

PMID- 25591108
TI  - The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune
      responses and cardiac fibrosis in dogs.
AB  - Trypanosoma cruzi infection may be caused by different strains with distinct
      discrete typing units (DTUs) that can result in variable clinical forms of
      chronic Chagas disease. The present study evaluates the immune response and
      cardiac lesions in dogs experimentally infected with different T. cruzi strains
      with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII
      DTU, respectively. During infection with the Col strain, increased levels of
      alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were
      observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood
      produced higher levels of interleukin (IL)-4. The latter suggests that during the
      acute phase, infection with the Col strain may remain unnoticed by circulating
      mononuclear cells. In the chronic phase, a significant increase in the number of
      inflammatory cells was detected in the right atrium. Conversely, infection with
      the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of
      CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain
      stimulated the production of interferon-gamma by CD4+ and CD8+ T-lymphocytes and
      IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and
      fibrosis were observed, demonstrating that strains of different DTUs interact
      differently with the host. 

PMID- 25591109
TI  - In vitro activity of the hydroethanolic extract and biflavonoids isolated from
      Selaginella sellowii on Leishmania (Leishmania) amazonensis.
AB  - This study is the first phytochemical investigation of Selaginella sellowii and
      demonstrates the antileishmanial activity of the hydroethanolic extract from this
      plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone,
      isolated from this species. The effects of these substances were evaluated on
      intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological
      agent of American cutaneous leishmaniasis. SSHE was highly active against
      intracellular amastigotes [the half maximum inhibitory concentration (IC50) =
      20.2 ug/mL]. Fractionation of the extract led to the isolation of the two
      bioflavonoids with the highest activity: amentoflavone, which was about 200 times
      more active (IC50 = 0.1 MUg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3
      MUg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index
      (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis
      (IC50 = 2.8 ug/mL), but more cytotoxic, with IC50 = 25.5 ug/mL (SI = 9.1) on
      NIH/3T3 cells and IC50 = 3.1 ug/mL (SI = 1.1) on J774.A1 cells. The production of
      nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that
      NO does not contribute to the leishmanicidal mechanism in this case), while NO
      release was higher after treatment with robustaflavone. S. sellowii may be a
      potential source of biflavonoids that could provide promising compounds for the
      treatment of cutaneous leishmaniasis. 

PMID- 25591110
TI  - Brazilian Angiostrongylus cantonensis haplotypes, ac8 and ac9, have two different
      biological and morphological profiles.
AB  - Angiostrongylus cantonensis is the etiologic agent of eosinophilic
      meningoencephalitis in humans. Cases have been recorded in many parts of the
      world, including Brazil. The aim of this study was to compare the differences in
      the biology and morphology of two different Brazilian haplotypes of A.
      cantonensis: ac8 and ac9. A significantly larger number of L1 larvae eliminated
      in the faeces of rodents at the beginning of the patent period was observed for
      ac9 haplotype and compared to the total of L1 larvae eliminated, there was a
      significant difference between the two haplotypes. The ac9 haplotype showed a
      significant difference in the proportion of female and male specimens (0.6:1),
      but the same was not observed for ac8 (1.2:1). The morphometric analysis showed
      that male and female specimens isolated from ac8 haplotype were significantly
      larger with respect to body length, oesophagus length, spicule length (male) and
      distance from the anus to the rear end (female) compared to specimens from ac9.
      The morphological analysis by light microscopy showed little variation in the
      level of bifurcations at the lateral rays in the right lobe of the copulatory
      bursa between the two haplotypes. The biological, morphological and morphometric
      variations observed between the two haplotypes agree with the observed variation
      at the molecular level using the cytochrome oxidase subunit I marker and
      reinforce the possible influence of geographical isolation on the development of
      these haplotypes.

PMID- 25591111
TI  - Effect of mouse antisera targeting the Phlebotomus papatasi midgut chitinase
      PpChit1 on sandfly physiology and fitness.
AB  - In sandflies, the absence of the peritrophic matrix (PM) affects the rate of
      blood digestion. Also, the kinetics of PM secretion varies according to species.
      We previously characterised PpChit1, a midgut-specific chitinase secreted in
      Phlebotomus papatasi (PPIS) that is involved in the maturation of the PM and
      showed that antibodies against PpChit1 reduce the chitinolytic activity in the
      midgut of several sandfly species. Here, sandflies were fed on red blood cells
      reconstituted with naive or anti-PpChit1 sera and assessed for fitness parameters
      that included blood digestion, oviposition onset, number of eggs laid, egg bouts,
      average number of eggs per bout and survival. In PPIS, anti-PpChit1 led to a one
      day delay in the onset of egg laying, with flies surviving three days longer
      compared to the control group. Anti-PpChit1 also had a negative effect on overall
      ability of flies to lay eggs, as several gravid females from all three species
      were unable to lay any eggs despite having lived longer than control flies.
      Whereas the longer survival might be associated with improved haeme scavenging
      ability by the PM, the inability of females to lay eggs is possibly linked to
      changes in PM permeability affecting nutrient absorption. 

PMID- 25591113
TI  - Landscape fragmentation and Ebola outbreaks.

PMID- 25591112
TI  - She's a femme fatale: low-density larval development produces good disease
      vectors.
AB  - Two hypotheses for how conditions for larval mosquitoes affect vectorial capacity
      make opposite predictions about the relationship of adult size and frequency of
      infection with vector-borne pathogens. Competition among larvae produces small
      adult females. The competition-susceptibility hypothesis postulates that small
      females are more susceptible to infection and predicts frequency of infection
      should decrease with size. The competition-longevity hypothesis postulates that
      small females have lower longevity and lower probability of becoming competent to
      transmit the pathogen and thus predicts frequency of infection should increase
      with size. We tested these hypotheses for Aedes aegypti in Rio de Janeiro,
      Brazil, during a dengue outbreak. In the laboratory, longevity increases with
      size, then decreases at the largest sizes. For field-collected females,
      generalised linear mixed model comparisons showed that a model with a linear
      increase of frequency of dengue with size produced the best Akaike's information
      criterion with a correction for small sample sizes (AICc). Consensus prediction
      of three competing models indicated that frequency of infection increases
      monotonically with female size, consistent with the competition-longevity
      hypothesis. Site frequency of infection was not significantly related to site
      mean size of females. Thus, our data indicate that uncrowded, low competition
      conditions for larvae produce the females that are most likely to be important
      vectors of dengue. More generally, ecological conditions, particularly crowding
      and intraspecific competition among larvae, are likely to affect vector-borne
      pathogen transmission in nature, in this case via effects on longevity of
      resulting adults. Heterogeneity among individual vectors in likelihood of
      infection is a generally important outcome of ecological conditions impacting
      vectors as larvae. 

PMID- 25591115
TI  - Differential impact of stress on hypothalamic-pituitary-adrenal axis: gene
      expression changes in Lewis and Fisher rats.
AB  - The aim of the present work was to study the influence of variable stress on the
      expression of 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) and the
      neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2,
      UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase
      activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive
      Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific
      and strain-dependent differences in the basal and stress-stimulated expression of
      11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the
      prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was
      upregulated in the central amygdala and hippocampal CA2 and ventral but not
      dorsal CA1 region; no effect was observed in the paraventricular nucleus,
      pituitary gland and adrenal cortex of both strains. The expression of
      glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress also
      stimulated the expression of paraventricular OXT, CRH, UCN3 and PACAP in both
      strains but amygdalar CRH only in LEW and UCN2/UCN3 in F344 rats, respectively.
      The upregulation of PACAP and CRH was paralleled only by increased expression of
      PACAP receptor PAC1 but not CRH receptor type 1. These observations provide
      evidence that inbred F344 and LEW rats exhibit not only the well-known phenotypic
      differences in the activity of the HPA axis but also strain- and stress-dependent
      differences in the expression of genes encoding 11HSD1 and neuropeptides
      associated with the HPA axis activity. Moreover, the differences in 11HSD1
      expression suggest different local concentration of corticosterone and access to
      GR in canonical and noncanonical structures of the HPA axis. 

PMID- 25591114
TI  - Fetal programming of children's obesity risk.
AB  - OBJECTIVE: Childhood obesity affects nearly 17% of children and adolescents in
      the United States. Increasing evidence indicates that prenatal maternal stress
      signals influence fetal growth, child obesity, and metabolic risk. Children
      exhibiting catch-up growth, a rapid and dramatic increase in body size, within
      the first two years of life are also at an increased risk for developing
      metabolic disorder and obesity. We evaluate the potential role of the maternal
      hypothalamic-pituitary-adrenal (HPA) and placental axis in programming risk for
      child obesity. METHOD: This prospective longitudinal study measured placental
      corticotropin-releasing hormone (pCRH) and maternal plasma cortisol at 15, 19,
      25, 30, and 37 gestational weeks and collected child body mass index (BMI) at
      birth, 3, 6, 12, and 24 months. Participants included 246 mothers and their
      healthy children born full term. Each child's BMI percentile (BMIP) was
      determined using World Health Organization (WHO) standards based on age and sex.
      Child BMIP profiles from birth to two years of age were characterized using
      general growth mixture modeling (GGMM). We evaluated whether fetal exposure to
      placental CRH and maternal cortisol are associated with BMIP profiles. RESULTS:
      Placental CRH at 30 gestational weeks was highly associated with both BMIP
      (p<.05) and weight (p<.05) at birth when accounting for gestational age at birth
      and used as a predictor in modeling BMIP profiles. Maternal cortisol was not
      associated with child BMIP. GGMM analyses identified four distinct BMIP profiles:
      typical, rapid increase, delayed increase, and decreasing (See Fig. 2). The
      typical profile comprised the majority of the sample and maintained BMIP across
      the first two years. The rapid and delayed increase profiles each exhibit a
      period of reduced body size followed by BMI catch-up growth. The rapid increase
      profile exhibited catch-up within the first 12 months while the delayed group
      showed an initial decrease in BMIP at 3 months and a dramatic increase from 12 to
      24 months. The decreasing profile exhibited normal birth weight and BMIP followed
      by persisting, low BMIP. The members of the rapid and delayed increase profiles
      were exposed to the highest concentrations of placental CRH at 30 gestational
      weeks compared to those in the typical profile group (Fig. 3). CONCLUSIONS:
      Exposure to elevated placental CRH concentrations during the third trimester is
      associated with catch-up growth. An early period of small body size followed by
      rapid catch-up growth is a profile associated with increased metabolic risk and
      increased obesity risk. Our findings suggest that placental CRH exposure makes a
      unique contribution to fetal programming of obesity risk.

PMID- 25591117
TI  - High-performance organic small-molecule panchromatic photodetectors.
AB  - High-performance panchromatic organic photodetectors (OPDs) containing small
      molecules lead phthalocyanine (PbPc) and C70 fullerene as donor and acceptor,
      respectively, were demonstrated. The OPDs had either a PbPc/C70 planar
      heterojunction (PHJ) or a PbPc/PbPc:C70/C70 hybrid planar-mixed molecular
      heterojunction (PM-HJ) structure. Both the PHJ and the PM-HJ devices showed a
      broad-band response that covered wavelengths from 300 to 1100 nm. An external
      quantum efficiency (EQE) higher than 10% and detectivity on the order of 10(12)
      Jones were obtained in the wavelength region from 400 to 900 nm for the PHJ
      device. The EQE in the near-infrared region was enhanced by using the PM-HJ
      device structure, and a maximum EQE of 30.2% at 890 nm was observed for the
      optimized device with a 5% PbPc-doped C70 layer. Such an EQE is the highest at
      this wavelength of reported OPDs. The detectivity of the PM-HJ devices was also
      higher than that of the PHJ one, which is attributed to the increased efficiency
      of exciton dissociation in bulk heterojunction structure, increased absorption
      efficiency caused by formation of triclinic PbPc in the PbPc:C70 mixed film when
      it was deposited on a pristine PbPc layer, and high hole mobility of the PbPc
      doped C70 layer. 

PMID- 25591116
TI  - Habitual sleep-wake behaviors and lifestyle as predictors of diurnal cortisol
      patterns in young breast cancer survivors: a longitudinal study.
AB  - OBJECTIVE: This study aimed to identify predictors of changes in diurnal cortisol
      patterns during the 8-month follow up period for young breast cancer survivors.
      Among the potential predictors were tumor size, lymph node metastasis, changes in
      sleep problems, habitual time of awakening and bedtime, physical activity levels,
      body mass index (BMI), and depressive levels across 8 months. METHODS: The
      participants were 62 breast cancer women who were aged 40 years and below, and
      had completed active breast cancer treatment. The longitudinal data were
      collected at four points: baseline assessment (T0) and three follow-ups after
      baseline: T1 (in the 2nd month), T2 (in the 5th month), and T3 (in the 8th
      month). The participants collected their salivary cortisol at home at six time
      points: upon waking, 30 and 45min after waking, and at 1200h, 1700h, and 2100h.
      They also completed several questionnaires: the Medical Outcomes Study Sleep
      scale; the Beck Depression Inventory-II, physical activity levels on a 10-point
      scale, time of going to bed, time of awakening, and total sleep hours. RESULTS:
      This study found that the main predictors of changes toward flatter diurnal
      cortisol patterns during the 8-month follow ups were greater tumor sizes,
      increases of BMI scores, and habitually later times of awakening. CONCLUSIONS:
      While greater tumor sizes represent biological vulnerability of disruption of
      cortisol circadian rhythm, maintaining an appropriate BMI and good sleep habits
      could be a protective factor for normal cortisol regulation, which likely helps
      to reduce early mortality in young breast cancer survivors.

PMID- 25591118
TI  - Spatial resolution recovery utilizing multi-ray tracing and graphic processing
      unit in PET image reconstruction.
AB  - Depth-of-interaction (DOI) poses a major challenge for a PET system to achieve
      uniform spatial resolution across the field-of-view, particularly for small
      animal and organ-dedicated PET systems. In this work, we implemented an
      analytical method to model system matrix for resolution recovery, which was then
      incorporated in PET image reconstruction on a graphical processing unit platform,
      due to its parallel processing capacity. The method utilizes the concepts of
      virtual DOI layers and multi-ray tracing to calculate the coincidence detection
      response function for a given line-of-response. The accuracy of the proposed
      method was validated for a small-bore PET insert to be used for simultaneous
      PET/MR breast imaging. In addition, the performance comparisons were studied
      among the following three cases: 1) no physical DOI and no resolution modeling;
      2) two physical DOI layers and no resolution modeling; and 3) no physical DOI
      design but with a different number of virtual DOI layers. The image quality was
      quantitatively evaluated in terms of spatial resolution (full-width-half-maximum
      and position offset), contrast recovery coefficient and noise. The results
      indicate that the proposed method has the potential to be used as an alternative
      to other physical DOI designs and achieve comparable imaging performances, while
      reducing detector/system design cost and complexity. 

PMID- 25591119
TI  - Kinase inhibitor profile for human nek1, nek6, and nek7 and analysis of the
      structural basis for inhibitor specificity.
AB  - Human Neks are a conserved protein kinase family related to cell cycle
      progression and cell division and are considered potential drug targets for the
      treatment of cancer and other pathologies. We screened the activation loop mutant
      kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different
      activation/phosphorylation statesand compared them against 85 compounds using
      thermal shift denaturation. We identified three compounds with significant Tm
      shifts: JNK Inhibitor II for hNek1(Delta262-1258)-(T162A), Isogranulatimide for
      hNek6(S206A), andGSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds
      was also validated by reducing the kinases activity by at least 25%. The binding
      sites for these compounds were identified by in silico docking at the ATP-binding
      site of the respective hNeks. Potential inhibitors were first screened by thermal
      shift assays, had their efficiency tested by a kinase assay, and were finally
      analyzed by molecular docking. Our findings corroborate the idea of ATP
      competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive
      inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate
      that our approach is useful for finding promising general and specific
      hNekscandidate inhibitors, which may also function as scaffolds to design more
      potent and selective inhibitors. 

PMID- 25591121
TI  - Pro-moieties of antimicrobial peptide prodrugs.
AB  - Antimicrobial peptides (AMPs) are a promising class of antimicrobial agents that
      have been garnering increasing attention as resistance renders many conventional
      antibiotics ineffective. Extensive research has resulted in a large library of
      highly-active AMPs. However, several issues serve as an impediment to their
      clinical development, not least the issue of host toxicity. An approach that may
      allow otherwise cytotoxic AMPs to be used is to deliver them as a prodrug,
      targeting antimicrobial activity and limiting toxic effects on the host. The
      varied library of AMPs is complemented by a selection of different possible pro
      moieties, each with their own characteristics. This review deals with the
      different pro-moieties that have been used with AMPs and discusses the merits of
      each. 

PMID- 25591120
TI  - Linking protein motion to enzyme catalysis.
AB  - Enzyme motions on a broad range of time scales can play an important role in
      various intra- and intermolecular events, including substrate binding, catalysis
      of the chemical conversion, and product release. The relationship between protein
      motions and catalytic activity is of contemporary interest in enzymology. To
      understand the factors influencing the rates of enzyme-catalyzed reactions, the
      dynamics of the protein-solvent-ligand complex must be considered. The current
      review presents two case studies of enzymes-dihydrofolate reductase (DHFR) and
      thymidylate synthase (TSase)-and discusses the role of protein motions in their
      catalyzed reactions. Specifically, we will discuss the utility of kinetic isotope
      effects (KIEs) and their temperature dependence as tools in probing such
      phenomena. 

PMID- 25591122
TI  - Chemical composition and antioxidant activity in different tissues of brassica
      vegetables.
AB  - This research was conducted to evaluate glucosinolate profiles, vitamin C, total
      phenol, total flavonoid, and free sugar (glucose, fructose, and sucrose) content,
      fatty acid composition, and antioxidant activity in floret and leaf of six
      cauliflower and broccoli cultivars. The level of chemical constituents as well as
      antioxidants significantly varied among crop types, cultivars, and their
      different parts, in that phytochemicals such as glucosinolate were statistically
      higher in florets compared with leaves in both broccoli and cauliflower
      cultivars. In contrast, total flavonoid and free sugar were found at higher
      levels in the leaf parts. The Asia purple cultivar exhibited statistically higher
      vitamin C (649.7 mg.100 g-1), total phenol (1345.2 mg.GAE 100 g-1), and total
      flavonoid (632.7 mg.CE 100 g-1) contents and consequently had the highest
      antioxidant activity (1.12 mg.mL-1) in its florets, while Baeridom and Bridal had
      the highest total glucosinolate (9.66 umol.g-1) and free sugar (318.6 mg.g-1)
      contents, respectively compared with other cultivars. Likewise, the major fatty
      acids were palmitic (23.52%-38.42%), linoleic (13.09%-18.97%), and linolenic
      (26.32%-51.80%) acids, which comprised the highest compositional ratio (more than
      50%) of polyunsaturated fatty acids (PUFAs) in most cultivars. Among the
      antioxidants, total phenol exhibited the most significant positive correlation (r
      = 0.698 **) with antioxidant activity, followed by vitamin C (r = 0.522 **) and
      total flavonoid (r = 0.494 **), indicating their significant contributions to
      total antioxidant activity. 

PMID- 25591123
TI  - Indications and limitations of bariatric intervention in severely obese children
      and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN Hepatology
      Committee Position Statement.
AB  - Morbid obesity is strongly associated with nonalcoholic fatty liver disease
      (NAFLD), which is one of the most common causes of chronic liver disease
      worldwide. The present best treatment for NAFLD and nonalcoholic steatohepatitis
      (NASH) is weight reduction through lifestyle modification. Because of frustrating
      inefficiency of such a therapeutic approach, bariatric surgery is increasingly
      performed in adolescents as an alternative option for weight reduction. Standards
      of care and consensus for indications are, however, scarce. We explore the
      indications and limitations of bariatric surgery in children with severe obesity
      with and without NASH and aim to provide guidance for the exceptional indications
      for adolescents with extreme obesity with major comorbidity that may benefit from
      these controversial interventions. Present evidence suggests that bariatric
      surgery can decrease the grade of steatosis, hepatic inflammation, and fibrosis
      in NASH. Uncomplicated NAFLD is not an indication for bariatric surgery. Roux-en
      Y gastric bypass is considered a safe and effective option for adolescents with
      extreme obesity, as long as an appropriate long-term follow-up is provided.
      Laparoscopic adjustable gastric banding has not been approved by the Food and
      Drug Administration for use in adolescents and therefore should be considered
      investigational. Finally, sleeve gastrectomy and other types of weight loss
      surgery that have grown increasingly common in adults, still need to be
      considered investigational. Temporary devices may be increasingly being used in
      pediatrics; however, future studies, including a long-term risk analysis of
      patients who undergo surgery, are much needed to clarify the exact indications
      for bariatric surgery in adolescents. 

PMID- 25591124
TI  - Consumption-weighted life cycle assessment of a consumer electronic product
      community.
AB  - A new approach for quantifying the net environmental impact of a "community" of
      interrelated products is demonstrated for consumer electronics owned by an
      average U.S. household over a 15-year period (1992-2007). This consumption
      weighted life cycle assessment (LCA) methodology accounts for both product
      consumption (number of products per household) and impact (cumulative energy
      demand (MJ) and greenhouse gas emissions (MT CO2 eq) per product), analyzed using
      a hybrid LCA framework. Despite efficiency improvements in individual devices
      from 1992 to 2007, the net impact of the entire product community increased, due
      primarily to increasing ownership and usage. The net energy impact for the
      product community is significant, nearly 30% of the average gasoline use in a
      U.S. passenger vehicle in 2007. The analysis points to a large contribution by
      legacy products (cathode ray tube televisions and desktop computers), due to
      historically high consumption rates, although impacts are beginning to shift to
      smaller mobile devices. This method is also applied to evaluate prospective
      intervention strategies, indicating that environmental impact can be reduced by
      strategies such as lifespan extension or energy efficiency, but only when applied
      to all products owned, or by transforming consumption trends toward fewer, highly
      multifunctional products. 

PMID- 25591125
TI  - Codelivery of DNA and siRNA via arginine-rich PEI-based polyplexes.
AB  - In this study, we formulated polyplexes with different compositions for
      codelivery of DNA and small-interfering RNA (siRNA). Since DNA and siRNA have
      distinctive and complementary morphological characteristics (DNA is long and
      winding and siRNA is short and rigid), we hypothesized that their codelivery
      using polyplex would enhance each other's transfection. To test this hypothesis,
      cationic polymer branched polyethylenimine (bPEI) as a standard transfecting
      agent and its derivative arginine-rich oligopeptide-grafted bPEI modified with
      polyethylene glycol (P(SiDAAr)5P3), synthesized in our laboratory, were used as
      carriers for transfection. Polyplexes at different nucleic acid to polymer weight
      ratios were characterized for transfection in breast cancer sensitive (MCF-7) and
      resistant (MCF-7/Adr) cell lines. Gene silencing effect of polyplexes was
      determined in MDA-MB-231-luc-D3H2LN cell line. The results demonstrated that the
      polyplexes formed with derivative P(SiDAAr)5P3 show significantly lower toxicity
      compared to polyplexes formed using bPEI. Further, codelivery resulted in 20-fold
      higher DNA transfection and 2-fold higher siRNA transfection as compared to the
      respective single nucleotide delivery. DNA transfection was ~100-fold lower in
      resistant MCF-7/Adr cells than in sensitive MCF-7 cells. Confocal imaging and
      flow cytometry data demonstrated that enhanced transfection does not solely
      depend on DNA's cellular uptake, suggesting that other mechanisms contribute to
      increased transfection. DNA-co-siRNA delivery could be a promising therapeutic
      approach to achieve synergistic effects because it can simultaneously target and
      interfere with multiple regulatory levels in a cell to halt and reverse disease
      progression. 

PMID- 25591126
TI  - Rapid Maxillary Expansion Increases Internal Nasal Dimensions of Children With
      Bilateral Cleft Lip and Palate.
AB  - OBJECTIVE: The transverse maxillary deficiency frequently observed in patients
      with cleft lip and palate (CLP) is usually treated by rapid maxillary expansion
      (RME). Considering that RME causes a significant increase of the internal nasal
      dimensions in children with unilateral CLP (UCLP), this study aimed to
      characterize the internal nasal geometry of children with bilateral CLP (BCLP)
      and transverse maxillary deficiency using acoustic rhinometry. The study also
      aimed to analyze changes caused by RME. DESIGN: Cross-sectional prospective
      study. SETTING: Laboratory of Physiology, Hospital for Rehabilitation of
      Craniofacial Anomalies, University of Sao Paulo, Bauru, SP, Brazil. PARTICIPANTS:
      Fifteen children with repaired BCLP of both genders, aged 8 to 15 years, referred
      for RME, were prospectively analyzed. INTERVENTIONS: Subjects underwent acoustic
      rhinometry before the expander installation and after the active phase of
      expansion. Cross-sectional areas (CSA) and volumes (V) of the nasal valve regions
      (CSA1 and V1) and turbinates (CSA2, CSA3, and V2), were measured after nasal
      decongestion. MAIN OUTCOME MEASURES: In the majority of the subjects, an increase
      of internal nasal dimensions was observed. RESULTS: Percent changes of CSA1,
      CSA2, CSA3, V1, and V2 were: +25%, +11%, +9%, 20%, and +12%, respectively.
      Differences were significant for all variables studied, except CSA3 (P < .05).
      CONCLUSIONS: RME promotes an increase in the internal nasal dimensions of
      children with BCLP, suggesting that RME is capable of substantially improving
      nasal patency in this population.

PMID- 25591127
TI  - Secondary Alveolar Bone Grafting (CLEFTSiS) 2007-2010.
AB  - Objective :  To determine whether alveolar bone graft outcomes for unilateral and
      bilateral cleft lip and palate patients have continued to improve since the
      reorganization of cleft services in Scotland in 2000. Design :  Retrospective
      analysis of postoperative anterior occlusal radiographs. Patients and
      Participants :  Eighty-one of 106 patients who were eligible for alveolar bone
      grafting between 2007 and 2010 had suitable postoperative radiographs available.
      Interventions :  Twenty-seven percent of the patients (n = 22) had presurgical
      orthodontic intervention. All patients underwent alveolar bone grafting with bone
      harvested from the iliac crest. Main Outcome Measures :  The Kindelan bone-fill
      index was used to evaluate success. Weighted kappa statistics were used to assess
      intra- and interobserver reproducibility. A comparison was made with results from
      2000 to 2004 to assess any improvement. Chi-square tests (or Fisher exact test)
      were used to determine whether outcomes differed depending on the laterality of
      the cleft, use of presurgical expansion, or age at bone grafting. Results : 
      Interobserver scoring agreement was good (weighted kappa = .383). Intraobserver
      reproducibility was greater (weighted kappas of .835 and .620). Success was
      achieved in 99% of bone grafts, compared with 76% in the period from 2000 to 2004
      (P < .001). There was no statistically significant relationship between the
      laterality of the cleft (P = 1.000), use of presurgical expansion (P = 1.000), or
      age at time of bone grafting and outcome (P = .259). Conclusion :  Scottish
      secondary alveolar bone graft outcomes improved during 2007 to 2010 in comparison
      to the 2000 to 2004 results.

PMID- 25591128
TI  - Color-coded cerebral computed tomographic angiography: implementation of a
      convolution-based algorithm and first clinical evaluation in patients with acute
      ischemic stroke.
AB  - OBJECTIVE: The objective of this study was to develop a new method of displaying
      dynamic cerebral computed tomographic (CT) angiography (CTA) data sets in which
      the time delay to maximum enhancement (Tdelay) is displayed in a range of colors
      (color-coded CT angiography [cCTA]). MATERIALS AND METHODS: This institutional
      review board-approved study included multiparametric CT data sets from 16
      patients with different types of supra-aortic large vessel occlusions. Color
      coded CT angiography was reconstructed from CT perfusion raw data sets. All voxel
      enhancement curves were fitted to f(t) = alpha . AIFmtt(t - Deltat), with
      AIFmtt(t), indicating enhancement of AIF dilated by convolution with boxcar
      function (with mean transit time [mtt]); alpha, scaling factor; and [INCREMENT]t,
      transition along the time. The time delay to maximum enhancement was defined as
      Tdelay = Deltat +0.5 . mtt. Values of Tdelay were color-coded and superimposed on
      temporal maximum intensity projections CTA resulting in colored angiographic
      composite images. For a pilot clinical evaluation, diagnostic confidence in
      determining the pathology, quality of the visualization of leptomeningeal
      collaterals, and additional diagnostic information were assessed. RESULTS: The
      reconstruction of cCTA was technically feasible in all 16 patients. Both
      diagnostic confidence (P < 0.01) and the quality of the visualization of
      collaterals (P < 0.0001) were significantly higher when using the combination of
      single-phase CTA and cCTA compared with single-phase CTA alone. Additional
      diagnostic information was obtained with cCTA regarding occlusion type (reader 1:
      5 cases and reader 2: 4 cases), differentiation between arteries and veins
      (11/13), differentiation between antegrade and retrograde filling (12/13), as
      well as leptomeningeal collateralization (13/14). CONCLUSIONS: Color-coded CT
      angiography is a technically feasible technique that provides additional
      information on cerebral hemodynamics in ischemic stroke patients.

PMID- 25591129
TI  - Automated tube voltage selection in thoracoabdominal computed tomography at high
      pitch using a third-generation dual-source scanner: image quality and radiation
      dose performance.
AB  - OBJECTIVES: The objective of this study was to evaluate the radiation dose and
      image quality performance of thoracoabdominal examinations with an automated tube
      voltage selection (tube voltage adaptation), tube current modulation, and high
      pitch using a third-generation dual-source computed tomography (CT) compared
      intraindividually with 120-kV examinations with tube current modulation with
      special attention on clinically relevant lesions in the liver, the lungs, and
      extrahepatic soft tissues. MATERIALS AND METHODS: This study was approved by the
      institutional review board. Computed tomography of the body was performed using a
      third-generation dual-source system in 95 patients (mean body mass index, 25
      kg/m2; range, 18-35 kg/m2). For 49 of these patients, all calculated tube
      settings and resulting dose values were recorded for each of the 12 gradual
      contrast weightings of the tube voltage adaptation algorithm. Spiral CT was
      performed for all patients with an intermediate weighting (grade 7) in a portal
      venous phase at 120 reference kV, 180 reference mAs, and pitch of 1.55. Objective
      image quality was assessed on the basis of contrast-to-noise ratio. Subjective
      image quality was assessed on the basis of clarity and sharpness of anatomical
      and pathological structures as well as interfering beam hardening and spiral and
      motion artifacts (heart, lungs, diaphragm). Previous examinations on a 64-slice
      scanner served as reference. RESULTS: All examinations were rated good or
      excellent for clinical diagnosis. Automated tube voltage selection resulted in
      significantly lower effective radiation dose (9.5 mSv) compared with the
      reference (12.0 mSv; P < 0.01). Contrast-to-noise ratio and image quality of soft
      tissue lesions were significantly increased (P < 0.01). Motion artifacts were
      significantly reduced (P < 0.01). CONCLUSIONS: Automated tube voltage adaptation
      combined with high-pitch protocols allows for a substantial radiation dose
      reduction while substantially increasing the image quality, even at large-volume
      exposure.

PMID- 25591130
TI  - Efficacy of Hip Strengthening Exercises Compared With Leg Strengthening Exercises
      on Knee Pain, Function, and Quality of Life in Patients With Knee Osteoarthritis.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of hip and leg
      strengthening exercise programs on knee pain, function, and quality of life (QOL)
      of patients with knee osteoarthritis (KOA). DESIGN: Single-Blinded Randomized
      Clinical Trial. SETTING: Patients with KOA. PARTICIPANTS: Male and female
      subjects were recruited from patients referred to the University of Calgary Sport
      Medicine Center and from newspaper advertisements. INTERVENTIONS: Thirty-seven
      and 35 patients with KOA were randomly assigned to either a 12-week hip or leg
      strengthening exercise program, respectively. Both exercise programs consisted of
      strengthening and flexibility exercises, which were completed 3 to 5 days a week.
      The first 3 weeks of exercise were supervised and the remaining 9 weeks consisted
      of at-home exercise. MAIN OUTCOME MEASURES: Knee Injury and Osteoarthritis Score
      (KOOS) and Western Ontario McMaster Arthritis Index (WOMAC) questionnaires, 6
      minute walk test, hip and knee range of motion (ROM), and hip and leg muscle
      strength. RESULTS: Statistically and clinically significant improvements in the
      KOOS and WOMAC pain subscale scores were observed in both the hip and leg
      strengthening programs. There was no statistical difference in the change in
      scores observed between the 2 groups. Equal improvements in the KOOS and WOMAC
      function and QOL subscales were observed for both programs. There was no change
      in hip and knee ROM or hip and leg strength in either group. CONCLUSIONS:
      Isolated hip and leg strengthening exercise programs seem to similarly improve
      knee pain, function, and QOL in patients with KOA. CLINICAL RELEVANCE: The
      results of this study show that both hip and leg strengthening exercises improve
      pain and QOL in patients with KOA and should be incorporated into the exercise
      prescription of patients with KOA.

PMID- 25591131
TI  - Effects of Off-Axis Elliptical Training on Reducing Pain and Improving Knee
      Function in Individuals With Patellofemoral Pain.
AB  - OBJECTIVE: To examine whether an off-axis elliptical training program reduces
      pain and improves knee function in individuals with patellofemoral pain (PFP).
      DESIGN: Controlled laboratory study, pretest-posttest. SETTING: University
      rehabilitation center. PARTICIPANTS: Twelve adult subjects with PFP.
      INTERVENTIONS: Subjects with PFP completed an exercise program consisting of 18
      sessions of lower extremity off-axis training using a custom-made elliptical
      trainer that allows frontal plane sliding and transverse plane pivoting of the
      footplates. MAIN OUTCOME MEASURES: Changes in knee pain and function posttraining
      and 6 weeks after training were evaluated using the Knee Injury and
      Osteoarthritis Outcome Score (KOOS) and International Knee Documentation
      Committee (IKDC) scores. Lower extremity off-axis control was assessed by
      pivoting and sliding instability, calculated as the root mean square (RMS) of the
      footplate pivoting angle and sliding distance during elliptical exercise.
      Subjects' single-leg hop distance and proprioception in detecting lower extremity
      pivoting motion were also evaluated. RESULTS: Subjects reported significantly
      greater KOOS and IKDC scores (increased by 12-18 points) and hop distance
      (increased by 0.2 m) after training. A significant decrease in the pivoting and
      sliding RMS was also observed after training. Additionally, subjects with PFP
      demonstrated improved pivoting proprioception when tested under a minimum weight
      bearing position. CONCLUSIONS: An off-axis elliptical training program was
      effective in enhancing lower extremity neuromuscular control on the frontal and
      transverse planes, reducing pain, and improving knee function in persons with
      PFP. CLINICAL RELEVANCE: This study provides a novel intervention approach to
      enhance the control of the frontal and transverse plane motions of the lower
      extremities during functional weight-bearing activities. This novel off-axis
      elliptical training may be incorporated with other common treatment options
      currently available for PFP to augment the effects of musculoskeletal
      rehabilitation for the PFP population.

PMID- 25591132
TI  - Quantification of upper limb kinetic asymmetries in front crawl swimming.
AB  - This study aimed at quantifying upper limb kinetic asymmetries in maximal front
      crawl swimming and to examine if these asymmetries would affect the contribution
      of force exertion to swimming performance. Eighteen high level male swimmers with
      unilateral breathing patterns and sprint or middle distance specialists,
      volunteered as participants. A load-cell was used to quantify the forces exerted
      in water by completing a 30s maximal front crawl tethered swimming test and a
      maximal 50 m free swimming was considered as a performance criterion. Individual
      force-time curves were obtained to calculate the mean and maximum forces per
      cycle, for each upper limb. Following, symmetry index was estimated and breathing
      laterality identified by questionnaire. Lastly, the pattern of asymmetries along
      the test was estimated for each upper limb using linear regression of peak forces
      per cycle. Asymmetrical force exertion was observed in the majority of the
      swimmers (66.7%), with a total correspondence of breathing laterality opposite to
      the side of the force asymmetry. Forces exerted by the dominant upper limb
      presented a higher decrease than from the non-dominant. Very strong associations
      were found between exerted forces and swimming performance, when controlling the
      isolated effect of symmetry index. Results point that force asymmetries occur in
      the majority of the swimmers, and that these asymmetries are most evident in the
      first cycles of a maximum bout. Symmetry index stood up as an influencing factor
      on the contribution of tethered forces over swimming performance. Thus, to some
      extent, a certain degree of asymmetry is not critical for short swimming
      performance.

PMID- 25591135
TI  - Synthesis of (+/-)-aureol by bioinspired rearrangements.
AB  - A bioinspired and sustainable procedure for the straightforward synthesis of (+/
      )-aureol has been achieved in eight steps (14% overall yield) from epoxyfarnesol.
      The key steps are the titanocene(III)-catalyzed radical cascade cyclization of an
      epoxyfarnesol derivative and a biosynthetically inspired sequence of 1,2-hydride
      and methyl shifts. 

PMID- 25591136
TI  - Application of the DiversiLab system for tracing the source of the mixed
      infections caused by Cryptococcus neoformans var. grubii from a patient with
      systemic lupus erythematosus.
AB  - Two strains of Cryptococcus neoformans (PU 66 and PU112) were simultaneously
      isolated from a patient with systemic lupus erythematosus. We aimed to trace the
      source of the mixed infections. Multi-locus sequence typing (MLST) and the
      DiversiLab system analyses were performed on the 2 clinical and 23 environmental
      C. neoformans from pigeon droppings, 11 from the home (H1) the patient visited,
      12 from another home (H2) as control. All the strains were uniformly genotyped as
      C. neoformans var. grubii VNI. Clinical strain PU66 and all the H1 isolates had
      the same sequence type (ST) - ST5, while for PU112 a new ST was observed - ST265.
      However, there was only one single base of 7 MLST loci difference between PU66
      and PU112. Sequence types of the H2 strains were ST31 and ST297. DiversiLab
      analysis showed that strain similarity between the two clinical strains was
      96.7%. In relation to environmental samples, the highest strain similarity
      (99.3%) was observed for PU66 and PU70 (H1). However, none of the environmental
      isolates had similarity over 98.6% comparing to PU112. One source of the mixed
      infections has been detected, but another needs further investigation. 

PMID- 25591137
TI  - Treatment and outcome of lung cancer in idiopathic interstitial pneumonias.
AB  - BACKGROUND: Idiopathic interstitial pneumonias (IIP) are associated with an
      increased lung cancer (LC) risk. However, data on the prognostic and therapeutic
      impact are limited. We therefore aimed to analyze the outcome of IIP patients
      with LC under different treatment modalities. METHODS: Patients with IIPs
      diagnosed in a tertiary interstitial lung diseases (ILD) center were reviewed for
      LC diagnosis. RESULTS: Of 265 patients with idiopathic pulmonary fibrosis (IPF),
      142 with non-specific interstitial pneumonia (NSIP), and 71 with cryptogenic
      organizing pneumonia (COP), 16%, 4%, and 6% were affected byLC, respectively.
      Patient characteristics were: IPF: 93% male, median age 67 years, forced vital
      capacity (FVC) 82%, diffusion capacity for Carbon monoxide (DLCO) 41%, mean
      survival 20 months. NSIP: 67% male, median age 70 years, FVC 72%, DLCO 43%, mean
      survival 35 months. COP: 50% male, median age 66 years, FVC 93%, DLCO 77%, mean
      survival 88 months. Significant treatment-related toxicities occurred in 55% IPF,
      20% NSIP und 0% COP patients. 30-days postoperative mortality was 25% in IPF, and
      0% in NSIP/COP while rate of radiation pneumonitis was 24% in IPF. CONCLUSIONS:
      LC is a frequent comorbidity in IIP, with a higher incidence and reduced survival
      in IPF compared to other IIPs. LC treatment is associated with significant
      toxicity, specifically in IPF. Interdisciplinary evaluation of therapeutic
      options in IIP patients diagnosed with LC is therefore mandatory.

PMID- 25591138
TI  - Features of sarcoidosis associated with chronic disease.
AB  - BACKGROUND: The clinical outcome of sarcoidosis is variable. Several features
      have been proposed as predictive of chronic sarcoidosis. OBJECTIVES: To examine
      the predictive role of clinical features on the clinical outcome score (COS) of
      sarcoidosis patients five years after initial diagnosis. METHODS: A cohort of
      newly diagnosed sarcoidosis patients seen at one clinic were re-evaluated five
      years after initial diagnosis. The COS was determined at this five year time
      point and compared to initial age, race, sex, forced vital capacity (FVC) and
      chest roentgenogram. We also compared COS to whether patients had Lofgrens
      syndrome, lupus pernio, or cardiac disease and what treatment they received
      during the five years of observation. Patients with neurologic disease were
      divided into those with seventh cranial nerve paralysis alone versus those with
      other neurologic disease (CNS). RESULTS: Of the 335 newly diagnosed patients seen
      over a three year period, 213 (64%) were evaluated five years after initial
      diagnosis. Of these patients 168 (79%) were still requiring systemic therapy at
      five years (COS 7, 8, or 9). Seven features were associated with chronic disease:
      CNS alone (Odds Ratio (OR)=19.24, p<0.05); CNS, cardiac, and/or lupus pernio
      (OR=5.86, p<0.02); FVC<80% (OR=7.04, p<0.02); treatment with prednisone (OR=6.35,
      p<0.0001); methotrexate (OR=7.2, p<0.0001); azathioprine (OR=19.24, p<0.05); anti
      tumor necrosis therapy (OR=13.98, p>0.05). CONCLUSION: In our study, the majority
      of sarcoidosis patients were receiving systemic therapy five years after initial
      diagnosis. Patients with reduced lung function, neurologic disease, lupus pernio,
      and cardiac disease were more likely to require prolonged treatment.

PMID- 25591139
TI  - Sarcoidosis, a report from Guilan (an Iranian northen province) (2001-09).
AB  - BACKGROUND: Sarcoidosis is a chronic multiorgan autoimmune disorder that affects
      all racial and ethnic groups and occurs at all ages. OBJECTIVE: The aim of this
      study was to assess the clinical and epidemiological features of sarcoidosis
      patients in a referral clinic of pulmonary disease in city of Rasht (Guilan
      Iran). METHOD: This retrospective study was done by reviewing sarcoidosis
      patient's records containing demographic, sign and symptom and clinical data in a
      pulmonary clinic in Rasht from 2001-09. All statistical analyses were achieved
      using SPSS. RESULTS: most common signs and symptoms were respiratory, systemic
      and musculoskeletal complaints. According to Chest X-Ray, 61.3% had bilateral
      hilar lymphadenopathy (BHL) alone (stage 1), and 24.2% had BHL plus parenchymal
      involvment (stage 2). The most common abnormal finding in spirometry was small
      airway disease (20.3%).The follow-up data showed that 178 patients (45.2%) had
      significant improvement clinically, radiologically or both. CONCLUSION: It seems
      many clinical and radiological aspects of sarcoidosis in our patients are similar
      to other series. However, presentation with Lofgren's syndrome is a common
      feature and skin (n=48, 12.3%) and eye (n=19, 4.8%) involvement are less
      frequent. There is significant difference between west and east of Guilan in
      relation to referred patients (12.9 % vs 78.5% respectively).Of course this may
      be due to referral issues of patients and medical teamwork connections

PMID- 25591140
TI  - Association between idiopathic pulmonary fibrosis and coronary artery disease: a
      case-control study and cohort analysis.
AB  - BACKGROUND: Although the increased risk of coronary artery disease (CAD) in the
      patients with idiopathic pulmonary fibrosis (IPF) has been reported, there was
      few detailed information on the risk factors for CAD in IPF. The aim of this
      study was to investigate the prevalence of CAD in IPF with analysis of other risk
      factors. METHODS: The subjects were 460 patients (mean age, 65 years; 79% male;
      74% current or ex-smoker) diagnosed as IPF at Asan Medical Center and 1,925
      controls matched with age, gender, smoking habits, and date of IPF diagnosis from
      the cohort of Korean Heart Study. Cardiovascular risk factors and prevalence of
      CAD in both groups were compared and the incidence of newly developed CAD during
      follow-up was also analyzed. RESULTS: IPF group was more diabetic, and control
      group had a higher proportion of hypertension and hypercholesterolemia. The
      prevalence of CAD in IPF group (7%) was two times higher than that of control
      group (3%). Multivariate analysis revealed that age (OR, 1.04; 95% CI, 1.02
      1.07), hypertension (OR, 2.13; 95% CI, 1.36-3.33), hypercholesterolemia (OR,
      3.85; 95% CI, 2.51-5.88), and IPF (OR, 2.64; 95% CI, 1.68-4.14) were significant
      risk factors for CAD. During follow-up (median: 2.5 years for IPF and 4.4 years
      for controls), the incidence of newly diagnosed CAD was higher in the patients
      with IPF (6.8%) compared to controls (2.8%) (RR, 1.92; 95% CI, 1.08-3.43).
      CONCLUSIONS: IPF itself was an independent risk factor for CAD after the
      adjustment of age, hypertension, diabetes, and hypercholesterolemia.

PMID- 25591141
TI  - Pulmonary hypertension in idiopathic pulmonary fibrosis does not influence six
      minute walk distance: results from a retrospective study.
AB  - BACKGROUND: The characteristics of the six-minute walk test (6MWT) in patients
      with idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension (PH) have not
      yet been described; nevertheless, this test has already been used as a "surrogate
      end point" in some clinical trials. OBJECTIVE: Goal of this retrospective study
      was to assess whether the presence of PH in patients with IPF might influence
      6MWT performances. METHODS: We retrospectively reviewed the data of patients with
      IPF who were referred to our hospital. The study population was divided in two
      groups according to the presence or absence of PH at right heart catheterization;
      then, the six-minute walking distance (6MWD) and pulmonary function tests (PFTs)
      were compared between groups. RESULTS: Study population included 30 IPF patients
      with a mean age of 59.0 years (+/- 8.3), most of whom (76.7%) were males. A total
      of 43.3% of patients had PH. PFTs data were similar in IPF patients of the two
      groups; the only exception was FVC, which was significantly higher in IPF
      patients with PH (63.8% +/- 16.0 vs. 51.6% +/- 13.8 in patients without PH,
      p<0.05). No difference was detected between groups in 6MWD (222.3m +/- 118.5 in
      PH group and 222.1m +/- 118.5 in non-PH group, p>0.05). CONCLUSIONS: Our data
      suggested that 6MWD does not differ between IPF patients with or without PH.
      Thus, 6MWD should not be used as a surrogate endpoint in clinical study in
      patients affected by IPF and PH.

PMID- 25591142
TI  - Renal sarcoidosis: epidemiological and follow-up data in a cohort of 27 patients.
AB  - BACKGROUND: Renal sarcoidosis (RS) is a possible manifestation of systemic
      sarcoidosis. The clinical presentation can range from asymptomatic individuals up
      to acute renal failure with the necessity of renal replacement therapy. The
      definite diagnosis must be established by renal biopsy. OBJECTIVES: Demonstration
      of clinical characteristics and effectiveness of steroid treatment. METHODS: We
      present a single center study of 27 patients with histologically proven RS.
      Firstly, we elaborate on descriptive features such as extra-renal organ
      involvement, calcium levels, renal function, proteinuria and histological
      subtypes and provide an histological assessment of renal damage. Secondly, we
      present follow-up data over a period of 2 years or more. RESULTS: Non
      granulomatous tubulointerstitial nephritis (ngIN) was the most common
      histological entity (44%), followed by granulomatous IN (GIN, 30%), IgA-GN (26%)
      and nephrocalcinosis (11%). Under treatment with oral prednisone mean eGFR
      significantly improved from 38 +/- 21 ml/min to 57 +/- 26 ml/min and proteinuria
      decreased from 981 +/- 304 mg/24 hrs to 176 +/- 77 mg/24 hrs at the end of follow
      up. In total, 62.5% of patients responded to therapy. CONCLUSIONS: We
      demonstrated that GIN is more often associated with advanced stages of renal
      insufficiency than any other histological manifestation of RS. Furthermore,
      prednisone therapy is effective in improving eGFR and in reducing total urinary
      protein secretion. We suggest that the key prognostic factor for renal survival
      in RS is the early response to treatment.

PMID- 25591143
TI  - Activated CD8+ T cells and natural killer T cells in bronchoalveolar lavage fluid
      in hypersensitivity pneumonitis and sarcoidosis.
AB  - BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis are diffuse parenchymal
      lung diseases characterized by formation of non-caseating granulomas with a
      bronchocentric distribution. Analysis of the white blood cell differential
      profile in bronchoalveolar lavage fluid can be a useful supplement in the
      diagnostic work-up. OBJECTIVE: Diagnostic markers that can improve the
      discrimination of sarcoidosis and hypersensitivity pneumonitis are wanted.
      METHODS: Bronchoalveolar lavage fluid fractions of CD4+ and CD8+ T cells
      expressing the activation marker HLA-DR and fractions of natural killer T cells
      determined by flow cytometry were investigated in sarcoidosis (N=83),
      hypersensitivity pneumonitis (N=10) and healthy control subjects (N=15). RESULTS:
      In hypersensitivity pneumonitis, natural killer T cell fractions were over 7-fold
      greater [median (IQR): 5.5% (3.5-8.1) versus 0.7% (0.5-1.2), p<0.0001], and HLA
      DR+ fractions of CD8+ lymphocytes were almost two fold greater [median (IQR): 79%
      (75-82) versus 43% (34-52), p<0.0001] than in sarcoidosis. In healthy control
      subjects, natural killer T cell fractions of leucocytes and HLA-DR+ fractions of
      CD8+ lymphocytes were lower [median (IQR): 0.3% (0.3-0.6) and 30% (26-34), p=0.02
      and p=0.01 compared to sarcoidosis]. The combined use of these two markers seems
      to discriminate the diseases very well. CONCLUSION: This study suggests a role
      for the bronchoalveolar lavage fluid lymphocyte subsets HLA-DR+ CD8+ T cells and
      natural killer T cells in the diagnostic work up of sarcoidosis and
      hypersensitivity pneumonitis.

PMID- 25591144
TI  - Reconsideration of discrepancies between clinical and histopathological features
      in acute eosinophilic pneumonia.
AB  - BACKGROUND AND OBJECTIVES: Acute eosinophilic pneumonia (AEP) is a very rare
      condition, with only one paper published so far discussing histopathological
      findings at surgical biopsy. In that paper, AEP is considered to be an acute and
      proliferative stage of DAD accompanied by eosinophilia. However, acute
      respiratory distress syndrome, acute interstitial pneumonia, and acute
      exacerbation of idiopathic pulmonary fibrosis, which, unlike AEP are mostly life
      threatening diseases, also exhibit DAD. AEP also presents with severe hypoxia but
      rapidly improves on treatment with corticosteroids alone, without subsequent
      fibrosis. In contrast, the other above-mentioned diseases with the same
      histopathology show greatly different clinical courses. The reasons for these
      differences remain unclear. METHODS: Here we investigated the histopathology of
      AEP in 2 surgical lung biopsy and 14 transbronchial lung biopsy cases.
      Additionally, we determined the presence or absence of different phases of DAD by
      histopathology in these AEP cases. RESULTS AND CONCLUSION: Characteristic
      histopathological findings of AEP consist of alveolar edema with infiltration of
      eosinophils and lymphocytes and edema of perivascular area and interlobular
      septa. The alveolar spaces showed fibrinous exudates. There were no hyaline
      membranes or massive intraluminal fibrosis. These histopathological findings of
      interstitial edema and fluid exudates are consistent with radiological findings
      of lung edema and can explain the rapid and complete improvement.Because AEP does
      not exhibit lung fibrosis histopathologically, it should not to be included in
      DAD which is associated with lung fibrosis.

PMID- 25591145
TI  - In vitro and in vivo study of anti-tuberculosis effect of extracts isolated from
      Ranunculi Ternati Radix.
AB  - AIM: This study was designed to investigate the anti-tuberculosis activities of
      Ranunculi Ternati Radix extracts to demonstrate the effect of active part of
      Ranunculi Ternati Radix, which could be enriched through macroporous resin, on
      mycobacterium tuberculosis infections. MATERIALS AND METHODS: In vitro, the anti
      tuberculosis activity of its water extract (WE), 70% ethanol extract (EE), water
      eluted part of EE from D101 macroporous resin (WEPMR), 70% ethanol eluted part of
      EE from D101 macroporous resin (EEPMR) was conducted using H37Rv. Then EEPMR of
      better anti-tuberculosis activity was chosen to carry out anti-tuberculosis
      activity test against MDR2314-2 and XDR1220. In vivo, the anti-tuberculosis
      activities of EEPMR, Ranunculi Ternati Capsules and Isoniazid alone or in
      combination with different doses were evaluated on mouse model infected H37Rv.
      RESULTS: In vitro, EEPMR had inhibitory effect on H37Rv, MDR2314-2 and XDR1220.
      In vivo study, both medium and high dose of EEPMR alone had therapeutic effect on
      chronic tuberculosis in mouse. No acute toxicity was identified of EEPMR at a
      dose of 12.0 g.kg-1. CONCLUSIONS: EEPMR possessed better anti-tuberculosis
      effects than other extracts and Radix Ranunculi Ternati Capsules. This supported
      the use of macroporous resin to enrich the active part of Ranunculi Ternati Radix
      to cure mycobacterium tuberculosis infections.

PMID- 25591146
TI  - A pilot study: a combined therapy using polymyxin-B hemoperfusion and
      extracorporeal membrane oxygenation for acute exacerbation of interstitial
      pneumonia.
AB  - BACKGROUND: Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP)
      might be beneficial for treating acute exacerbation (AE) of interstitial
      pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an
      emerging tool to avoid ventilator-induced lung injury. This is a report
      presenting the first three patients with AE of IP treated with a combined therapy
      of PMX-DHP and VV-ECMO. CASE PRESENTATION: Patient 1 was a 68-year-old male with
      acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic
      pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen
      vascular disease-associated interstitial pneumonia. All patients were severely
      hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP
      and VV-ECMO was initiated with support of intravenous corticosteroids and
      antibiotics. Radiological findings, oxygenation and laboratory findings markedly
      improved and all patients survived without severe complications. CONCLUSION: A
      combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of
      IP.

PMID- 25591147
TI  - Granulomatous lung disease in a patient with a family history of hematological
      disorders.
AB  - BACKGROUND: A 29-year old patient presented with granulomatous lung disease and a
      family history of myelodysplastic syndrome/acute myeloid leukemia. She appeared
      to be a carrier of a mutation in the transcription factor GATA2. The case adds to
      the recent described heterogeneous clinical manifestations and syndromes in
      which, against a background of hematologic disorders, GATA2 mutations have been
      demonstrated, such as the Monomac and Emberger syndromes. In patients with a
      granulomatous disease and a history of (familial) hematologic disorders, the
      occurence of GATA2 mutations should be considered, as to gain further insight in
      the occurrence of granulomatous disease in a possible distinct phenotype among
      GATA2 mutation carriers.

PMID- 25591148
TI  - Intravascular large B cell lymphoma presenting in the lung: the diagnostic value
      of transbronchial cryobiopsy.
AB  - BACKGROUND AND OBJECTIVE: intravascular large B-cell lymphoma is a distinct
      subtype of mature B-cell neoplasms, with uncommon primary presentation in the
      lungs. Diagnosis could be very difficult due to the lack of detectable tumor
      masses and it is usually made by surgical lung biopsy or autopsy examination.
      METHODS: two patients occurred primarily with interstitial lung disease and
      underwent a pulmonary biopsy using cryoprobes. RESULTS: the pathological analysis
      of the lung biopsies revealed in both cases a conclusive diagnosis of
      intravascular large B-cell lymphoma with primary lung involvement and patients
      have been safely diagnosed using transbronchial cryobiopsy for the first time in
      the literature. CONCLUSIONS: transbronchial cryobiopsy could be used as valid
      surrogate for surgical lung biopsy in lymphoprolipherative lung disorders
      (including intravascular lymphomas), as allows larger samples of tissue, greater 
      diagnostic yield, no crush artifacts and much less complications than surgical
      biopsy. 

PMID- 25591149
TI  - Proceedings of the 2014 AASOG conference.

PMID- 25591150
TI  - Seasonal variation of serum KL-6 and SP-D levels in bird-related hypersensitivity
      pneumonitis.

PMID- 25591152
TI  - Research in inflammatory bowel diseases in Latin America: a challenge ahead.

PMID- 25591151
TI  - Investigating the spreading and toxicity of prion-like proteins using the
      metazoan model organism C. elegans.
AB  - Prions are unconventional self-propagating proteinaceous particles, devoid of any
      coding nucleic acid. These proteinaceous seeds serve as templates for the
      conversion and replication of their benign cellular isoform. Accumulating
      evidence suggests that many protein aggregates can act as self-propagating
      templates and corrupt the folding of cognate proteins. Although aggregates can be
      functional under certain circumstances, this process often leads to the
      disruption of the cellular protein homeostasis (proteostasis), eventually leading
      to devastating diseases such as Alzheimer's disease (AD), Parkinson's disease
      (PD), Amyotrophic lateral sclerosis (ALS), or transmissible spongiform
      encephalopathies (TSEs). The exact mechanisms of prion propagation and cell-to
      cell spreading of protein aggregates are still subjects of intense investigation.
      To further this knowledge, recently a new metazoan model in Caenorhabditis
      elegans, for expression of the prion domain of the cytosolic yeast prion protein
      Sup35 has been established. This prion model offers several advantages, as it
      allows direct monitoring of the fluorescently tagged prion domain in living
      animals and ease of genetic approaches. Described here are methods to study prion
      like behavior of protein aggregates and to identify modifiers of prion-induced
      toxicity using C. elegans. 

PMID- 25591153
TI  - Inflammatory bowel disease in Hispanic communities: a concerted South American
      approach could identify the aetiology of Crohn's disease and ulcerative colitis.
AB  - Despite intensive research we remain ignorant of the cause of both Crohn's
      disease and ulcerative colitis. The dramatic rise in incidence, particularly of
      Crohn's disease, points towards environmental factors as playing a significant
      role. A major purpose of this review is to stimulate a co-ordinated international
      effort to establish an on-going data base in Central and South America in which
      new cases are registered and through which investigations into aetiology can be
      conducted. In both Brazil and Mexico there is evidence that the incidence of
      ulcerative colitis is increasing, as also is the case for Crohn's disease in
      Brazil. The pattern of disease is, therefore, directly comparable to that
      reported from Europe and the USA during the 1970s and 1980s, but much lower than
      contemporary data from Spain. Although the incidence is similar to that reported
      from Portugal, the studies from Almada and Braga were conducted a decade before
      that from Sao Paulo. The situation in Brazil compares dramatically with Uruguay
      and Argentina where the reported incidence of inflammatory bowel disease is
      significantly less. However, with growing industrialisation it is likely that
      there will be an explosion of inflammatory bowel disease in some areas of Central
      and South America over the next 20 years. The creation of a network of
      researchers across South and Central America is a real possibility and through a
      Concerted Action there is the possibility that major strides could be made
      towards understanding the cause of inflammatory bowel disease and so develop
      preventive strategies. 

PMID- 25591154
TI  - Focal enhanced gastritis and macrophage microaggregates in the gastric mucosa:
      potential role in the differential diagnosis between Crohn's disease and
      ulcerative colitis.
AB  - CONTEXT AND OBJECTIVES: Focally enhanced gastritis and macrophage microaggregates
      are found in the upper gastrointestinal involvement of Crohn's disease, and may
      reflect an underlying defective innate immunity. These features, however, are
      also described in patients with Helicobacter pylori infection. The role of these
      gastric abnormalities in the diagnosis of Crohn's disease was assessed in a
      population with high prevalence of H. pylori infection. METHODS: Thirty-seven
      Crohn's disease, 26 ulcerative colitis, and 30 control patients were included.
      The H. pylori status was evaluated by the rapid urease test and histology. The
      presence of focally enhanced gastritis and macrophage microaggregates was
      recorded. RESULTS: Focally enhanced gastritis was present in 24% of Crohn's
      disease patients, 4% of ulcerative colitis patients and 11.5% of controls,
      presenting an overall sensitivity and specificity for Crohn's disease of 24% and
      88%, respectively. Macrophage microaggregates were found in all groups, but were
      only detected in ulcerative colitis and controls in association with H. pylori
      infection, with an overall sensitivity and specificity for Crohn's disease of 61%
      and 69%, respectively. In the absence of H. pylori infection, focally enhanced
      gastritis and macrophage microaggregates were significantly associated with
      Crohn's disease (P<0.02 and P = 0.001 respectively). CONCLUSIONS: Focally
      gastritis and macrophage microaggregates are suggestive of Crohn's disease only
      in H. pylori-negative specimens.

PMID- 25591155
TI  - Perianal complete remission with combined therapy (seton placement and anti-TNF
      agents) in Crohn's disease: a Brazilian multicenter observational study.
AB  - BACKGROUND: Perianal fistulizing Crohn's disease is one of the most severe
      phenotypes of inflammatory bowel diseases. Combined therapy with seton placement
      and anti-TNF therapy is the most common strategy for this condition. OBJECTIVES:
      The aim of this study was to analyze the rates of complete perianal remission
      after combined therapy for perianal fistulizing Crohn's disease. METHODS: This
      was a retrospective observational study with perianal fistulizing Crohn's disease
      patients submitted to combined therapy from four inflammatory bowel diseases
      referral centers. We analyzed patients' demographic characteristics, Montreal
      classification, concomitant medication, classification of the fistulae,
      occurrence of perianal complete remission and recurrence after remission.
      Complete perianal remission was defined as absence of drainage from the fistulae
      associated with seton removal. DISCUSSION: A total of 78 patients were included,
      44 (55.8%) females with a mean age of 33.8 (+/-15) years. Most patients were
      treated with Infliximab, 66.2%, than with Adalimumab, 33.8%. Complex fistulae
      were found in 52/78 patients (66.7%). After a medium follow-up of 48.2 months,
      41/78 patients (52.6%) had complete perianal remission (95% CI: 43.5%-63.6%).
      Recurrence occurred in four (9.8%) patients (95% CI: 0.7%-18.8%) in an average
      period of 74.8 months. CONCLUSIONS: Combined therapy lead to favorable and
      durable results in perianal fistulizing Crohn's disease.

PMID- 25591156
TI  - Correlation of endoscopic and histological features in adults with suspected
      celiac disease in a referral center of Minas Gerais, Brazil.
AB  - CONTEXT: Clinical presentation of celiac disease is extremely variable and the
      diagnosis relies on serologic tests, mucosal intestinal biopsy and clinic and
      serologic response to a gluten-free diet. OBJECTIVES: To correlate the endoscopic
      and histological aspects of adult patients with suspicion of celiac disease and
      to evaluate the interobserver histological agreement. METHODS: Endoscopic aspects
      of 80 adult patients were evaluated and correlated with the histological features
      according the Marsh-Oberhuber classification system. The interobserver
      histological agreement was based on kappa values. RESULTS: The symptoms of the
      patients varied largely, with prominence for chronic diarrhea, present in 48
      (60%) patients. The endoscopic aspects related with the duodenal villous atrophy
      had been observed in 32 (40%) patients. There were confirmed 46 cases of celiac
      disease, with prevalence of 57.5%. The sensitivity, specificity, positive
      predictive value and negative predictive value of the endoscopic markers for
      celiac disease diagnosis were of 60.9%, 88.2%, 87.5% and 62.5%. There was
      moderate interobserver histological agreement (kappa = 0.46). CONCLUSIONS: The
      endoscopic markers of villous atrophy, although not diagnostic, had assisted in
      the suspicion and indication of the duodenal biopsies for diagnosis proposal.
      Histology is sometimes contradictory and new biopsies or opinion of another
      professional can provide greater diagnostic agreement.

PMID- 25591157
TI  - Comparison of fecal elastase 1 for exocrine pancreatic insufficiency evaluation
      between ex-alcoholics and chronic pancreatitis patients.
AB  - CONTEXT: Fecal elastase is a noninvasive test for pancreatic insufficiency
      diagnosis. OBJECTIVES: Evaluate the usefulness of fecal elastase 1 for the
      indication of exocrine pancreatic insufficiency among former alcohol addicts and
      patients with chronic pancreatitis. METHODS: Forty-three patients with chronic
      pancreatitis and thirty-three asymptomatic former alcohol addicts entered the
      study. The levels of fecal elastase 1 were measured using a commercial kit.
      Pancreatic imaging findings were used to categorize the groups. RESULTS: The
      levels of fecal elastase 1 were significantly lower in the patients than in the
      former alcohol addicts and in the group with tissue calcifications, duct
      alterations, or atrophy. With a cutoff level of 100 MUg/g, the sensitivity of
      fecal elastase 1 in chronic pancreatitis was 46.51% and its specificity was
      87.88% with a positive predictive value of 83.33% and a negative predictive value
      of 55.77%. When patients were stratified according to the severity of their
      pancreatitis, the sensitivity was 6.25% for mild pancreatitis and 70.37% for
      marked pancreatitis. CONCLUSION: Low level of fecal elastase 1 was associated
      with marked rather than mild chronic pancreatitis; however, it may be useful to
      indicate pancreatic exocrine insufficiency in asymptomatic former alcohol
      addicts.

PMID- 25591158
TI  - Nitric oxide interferes with hypoxia signaling during colonic inflammation.
AB  - CONTEXT: Intestinal inflammation can induce a local reduction in oxygen levels
      that triggers an adaptive response centered on the expression of hypoxia
      inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator,
      may interfere with hypoxia signaling. OBJECTIVES: We aimed to evaluate the role
      of nitric oxide in hypoxia signaling during colonic inflammation. METHODS:
      Colitis was induced by single (acute) or repeated (reactivated colitis)
      trinitrobenzenosulfonic acid administration in rats. In addition, one group of
      rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl
      ester hydrochloride to block nitric oxide synthase. Colitis was assessed by
      macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was
      determined using the oxygen-dependent probe, pimonidazole. The expression of HIF
      1alpha and HIF-induced factors (vascular endothelial growth factor - VEGF and
      apelin) was assessed using Western blotting. RESULTS: The single or repeated
      administration of trinitrobenzenosulfonic acid to rats induced colitis which was
      characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia
      was observed with both protocols. During acute colitis, HIF-1alpha expression was
      not increased, but VEGF and apelin were increased. HIF-1alpha expression was
      inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw
      Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis
      restored HIF-1alpha, VEGF and apelin expression. CONCLUSIONS: Nitric oxide could
      interfere with hypoxia signaling during reactivated colitis inflammation
      modifying the expression of proteins regulated by HIF-1alpha.

PMID- 25591159
TI  - Increase of glycosaminoglycans and metalloproteinases 2 and 9 in liver
      extracellular matrix on early stages of extrahepatic cholestasis.
AB  - CONTEXT: Cholestasis produces hepatocellular injury, leukocyte infiltration,
      ductular cells proliferation and fibrosis of liver parenchyma by extracellular
      matrix replacement. OBJECTIVE: Analyze bile duct ligation effect upon
      glycosaminoglycans content and matrix metalloproteinase (MMPs) activities.
      METHODS: Animals (6-8 weeks; n = 40) were euthanized 2, 7 or 14 days after bile
      duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver
      weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT),
      alkaline phosphatase (Alk-P), alanine and aspartate aminotransferases (ALT and
      AST), tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities,
      histopathology and glycosaminoglycans content. RESULTS: Cholestasis caused
      cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was
      neutrophil infiltration observed by the increasing of myeloperoxidase activity on
      7 (P = 0.0064) and 14 (P = 0.0002) groups which leads to the magnification of
      tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667), MMP-2 (P =
      0.0003) and MMP-9 (P<0.0001) activities on 14 days indicating matrix remodeling
      and establishment of inflammatory process. Bile duct ligation animals showed an
      increasing on dermatan sulfate and/or heparan sulfate content reflecting
      extracellular matrix production and growing mitosis due to parenchyma depletion.
      CONCLUSIONS: Cholestasis led to many changes on rats' liver parenchyma, as so as
      on its extracellular matrix, with major alterations on MMPs activities and
      glycosaminoglycans content.

PMID- 25591160
TI  - Occurrence and spatial distribution of hepatitis C in a Western Brazilian Amazon
      state.
AB  - CONTEXT: Hepatitis C causes a major impact on public health due to the high
      prevalence in the population. OBJECTIVES: Evaluate the epidemiological data of
      hepatitis C in the State of Rondonia, Brazil. METHODS: Data from hepatitis C were
      analyzed during the period 2002 to 2012, assigned by the Agency for Sanitary
      Vigilance of the State of Rondonia. The variables studied were: year of
      diagnosis, gender, age, associated disease, exposure to risk factors and clinical
      presentation. RESULTS: Eight hundred fifty-nine cases were reported during the
      study period. Of this total, 542 (63.1%) cases were male. In relation to age
      group, the one with the highest number of cases was between 40-59 years (54%),
      followed by 20-39 years (33.5%). In relation to sexually transmitted diseases
      (STDs) association, 1.8% of patients had HIV and 2.1% other type of sexually
      transmitted disease. About exposure to risk factors, 288 (28.1%) individuals were
      exposed to a surgical procedure. Was also analyzed the clinical form of the
      disease, 9.9% are in acute disease and 91.1% in the chronic phase. CONCLUSIONS:
      In the State of Rondonia, hepatitis C had a mean annual incidence of 5.1
      cases/100,000 inhabitants, similar to the national rate.

PMID- 25591161
TI  - Impact on quality of life, weight loss and comorbidities: a study comparing the
      biliopancreatic diversion with duodenal switch and the banded Roux-en-Y gastric
      bypass.
AB  - CONTEXT: Few studies have evaluated the results of different types of bariatric
      surgery using the Medical Outcome Study 36 - Health Survey Short-Form (SF-36)
      quality of life questionnaire, the Bariatric and Reporting Outcome System (BAROS)
      and the reviewed Moorehead-Ardelt Quality of Life II Questionnaire (M-A QoLQ II)
      that is part of BAROS. The Roux-en-Y gastric bypass (RYGB) is the most common
      morbid obesity surgery worldwide. However, there is evidence indicating that a
      biliopancreatic diversion with duodenal switch (DS) is more effective than RYGB
      in weight loss terms. OBJECTIVES: To evaluate the impact of different types of
      bariatric surgery on quality of life, comorbidities and weight loss. METHODS: Two
      groups of patients who underwent bariatric surgery conventional Banded Roux-en-Y
      gastric bypass (BRYGB) or DS were evaluated through monitoring at 12 to 36 months
      after surgery, as well as a control group of obese patients who had not undergone
      surgery. The tools used for this were SF-36, BAROS and M-A QoLQ II. The DS group
      consisted of 17 patients and the BRYGB group consisted of 20. The control group
      comprised 20 independent, morbidly obese individuals. RESULTS: The mean age of
      the patients in the groups was 45.18 in the DS group, 49.75 in the BRYGB group
      and 44.25 in the control group, with no significant difference. There was no
      difference in the ratio of men to women in the groups. The patients that had
      surgery showed a significant improvement in all domains of quality of life vs the
      control group. Comparing the two groups that underwent surgery, the DS group
      achieved better quality of life results in terms of "general state of health" and
      "pain", according to responses to the SF-36 tool, and in terms of "sexual
      interest", according to responses to the M-A QoLQ II tool. There was no
      significant difference among the three groups regarding the ratio of occurrence
      of comorbidities. In the groups that had surgery, the resolution of comorbidities
      was similar. The final classification according to the BAROS Protocol was
      excellent for the DS group and very good for the BRYGB group, with a statistical
      difference in favor of the DS group (P = 0.044*). There was no difference in the
      percentages of excess weight loss between the DS group (82.1%) and the BRYGB
      group (89.4%) (P = 0.376). CONCLUSIONS: A comparison of the performance of the
      groups, which were monitored from 12 to 36 months after surgery, showed that the
      two types of surgery are effective to improve quality of life, comorbidities and
      weight loss. The DS surgery produced better results in the quality of life
      evaluations regarding 2 of 8 domains according to the SF-36, and "sexual
      interest" according to the M-A QoLQ II. In the groups that had surgery, the
      patients showed high rates of comorbidity resolution. Weight loss was similar for
      the two surgical groups.

PMID- 25591162
TI  - Predictors for weight loss failure following Roux-en-Y gastric bypass.
AB  - CONTEXT: Weight loss failure is a widely recognized occurrence following Roux-en
      Y gastric bypass. OBJECTIVES: This study aims to identify predictors associated
      with weight loss failure. METHODS: It is a retrospective cohort which enrolled
      187 subjects who underwent RYGB. Comparisons were made between patients' features
      at baseline and 24 months after surgery. RESULTS: A weight loss failure rate of
      11.2% was found. Advanced age and diabetes were statistically associated with
      failure. CONCLUSIONS: The results found were close to previous reports. As weight
      loss failure represents an important concern, there is the possibility to perform
      revisional surgeries, which may emphasize the restrictive or malabsorptive
      characteristics of RYGB, leading to varied results. It is reinforced that weight
      loss cannot be used as the unique outcome to evaluate the success of surgery.

PMID- 25591163
TI  - Immediate preoperative nutritional status of patients with colorectal cancer: a
      warning.
AB  - CONTEXT: Weight loss and malnutrition are disorders observed in colorectal cancer
      patients. OBJECTIVES: We sought to evaluate the immediate preoperative
      nutritional status of patients with colorectal cancer. METHODS: This is a cross
      sectional clinical study conducted at a single center. Sixty-six consecutive
      patients in preoperative for elective surgical treatment were studied. The
      clinical history, socio-demographic data and nutritional status of the patients
      were evaluated using Subjective Global Assessment and objective (anthropometry)
      methods. The primary outcome measures were nutritional status classification as
      nourished or malnourished and the relationship between nutritional status and
      socio-demographic and clinical features. RESULTS: Most of patients exhibited left
      colon tumors and disease stage II. According to the Subjective Global Assessment,
      36.4% of patients were malnourished. Malnutrition ranged from 7.6% to 53%
      depending on the evaluation method used, with poor correlation to Subjective
      Global Assessment. The prevalence of malnutrition was significantly greater in
      females and non-married patients and in those with two or more symptoms of
      colorectal cancer. CONCLUSIONS: More than a third of patients in the immediate
      preoperative period for colorectal cancer exhibited malnutrition. Therefore,
      routine nutritional assessment is highly advisable so that appropriate measures
      may be taken to minimize the potential postoperative complications.

PMID- 25591164
TI  - Initial experience with endoscopic ultrasound-guided fine needle aspiration of
      renal masses: indications, applications and limitations.
AB  - CONTEXT: Tissue sampling of renal masses is traditionally performed via the
      percutaneous approach or laparoscopicaly. The utility of endoscopic ultrasound to
      biopsy renal lesions it remains unclear and few cases have been reported.
      OBJECTIVES: To evaluate the feasibility and outcome of endoscopic ultrasound fine
      needle aspiration of renal tumors. METHODS: Consecutive subjects undergoing
      attempted endoscopic ultrasound fine needle aspiration of a kidney mass after
      evaluation with computerized tomography or magnetic resonance. RESULTS: Ten
      procedures were performed in nine male patients (median age 54.7 years) on the
      right (n = 4) and left kidney (n = 4) and bilaterally (n = 1). Kidney masses
      (median diameter 55 mm ; range 13-160 mm) were located in the upper pole (n = 3),
      the lower pole (n = 2) and the mesorenal region (n = 3). In two cases, the mass
      involved more than one kidney region. Surgical resection confirmed renal cell
      carcinoma in six patients in whom pre-operative endoscopic ultrasound fine needle
      aspiration demonstrated renal cell carcinoma. No complications were reported.
      CONCLUSIONS: Endoscopic ultrasound fine needle aspiration appears as a safe and
      feasible procedure with good results and minimal morbidity.

PMID- 25591165
TI  - A bead-spring model for running and tumbling of flagellated swimmers: detailed
      predictions compared to experimental data for E. coli.
AB  - To study the swimming of the multi-flagellated bacterium Escherichia coli, we
      deploy a bead-spring hydrodynamic model (Watari and Larson 2010), whose body and
      flagellar geometry, motor torques, and motor reversals are adjusted to match the
      experimental observations of the Berg group (Turner et al. 2000; Darnton et al.
      2007) during both running and tumbling of the bacterium. In this model,
      hydrodynamic interactions, which drive swimming, flagellar bundling, and
      unbundling during swimming and tumbling, are imposed by treating the beads as
      Stokeslets, imposing torques and counter-torques on the body and flagellum at the
      flexible joint connecting them to represent the action of motor, and using the
      Rotne-Prager tensor to model their hydrodynamic interactions with other beads. We
      explore the behavior of coarse-grained (60-bead) and refined (120-bead) versions
      of the model, and show that predictions of running speed, helical and body
      rotation rates, body wobble rates and angles, average tumbling angles, range of
      tumbling angles, and flagellar re-bundling times are in good agreement with
      experimental observations by Berg and coworkers. We find that variation in
      tumbling angle arises from variation in flagellar number and location on the
      bacterial body, variations in polymorphic transitions of the filaments, and
      especially from variations in the duration of the tumbling time, which is roughly
      linearly correlated with tumbling time up to tumbling angles of around 40-50
      degrees  and more weakly thereafter. The accuracy of the model suggests its
      usefulness for future studies of swimming of other flagellated swimmers, for
      predictions of collective phenomena, and for tuning parameters of coarser-grained
      swimmer models to achieve greater realism. 

PMID- 25591166
TI  - Myocardial Dysfunction in Severe Sepsis and Septic Shock: No Correlation With
      Inflammatory Cytokines in Real-life Clinical Setting.
AB  - BACKGROUND: In vitro studies suggested that circulating inflammatory cytokines
      cause septic myocardial dysfunction. However, no in vivo clinical study has
      investigated whether serum inflammatory cytokine concentrations correlate with
      septic myocardial dysfunction. METHODS: Repeated echocardiograms and concurrent
      serum inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-18, tumor necrosis
      factor-alpha, and monocyte chemoattractant protein-1) and cardiac biomarkers
      (high-sensitivity [hs] troponin-T and N-terminal pro-B-type natriuretic peptide
      [NT-proBNP]) were examined in 105 patients with severe sepsis and septic shock.
      Cytokines and biomarkers were tested for correlations with systolic and diastolic
      dysfunction, sepsis severity, and mortality. RESULTS: Systolic dysfunction
      defined as reduced left ventricular ejection fraction (LVEF) < 50% or < 55% and
      diastolic dysfunction defined as e'-wave < 8 cm/s on tissue-Doppler imaging (TDI)
      or E/e'-ratio were found in 13 (12%), 24 (23%), 53 (50%), and 26 (25%) patients,
      respectively. Forty-four patients (42%) died in-hospital. All cytokines, except
      IL-1, correlated with Sequential Organ Failure Assessment and APACHE (Acute
      Physiology and Chronic Health Evaluation) II scores, and all cytokines predicted
      mortality. IL-10 and IL-18 independently predicted mortality among cytokines (OR
      = 3.1 and 28.3, P = .006 and < 0.0001). However, none of the cytokines correlated
      with LVEF, end-diastolic volume index (EDVI), stroke-volume index (SVI), or s'
      wave and e'-wave velocities on TDI (Pearson linear and Spearman rank [rho]
      nonlinear correlations). Similarly, no differences were found in cytokine
      concentrations between patients dichotomized to high vs low LVEF, EDVI, SVI, s'
      wave, or e'-wave (Mann-Whitney U tests). In contrast, NT-proBNP strongly
      correlated with both reduced LVEF and reduced e'-wave velocity, and hs-troponin-T
      correlated mainly with reduced e'-wave. CONCLUSIONS: Unlike cardiac biomarkers,
      none of the measured inflammatory cytokines correlates with systolic or diastolic
      myocardial dysfunction in severe sepsis or septic shock.

PMID- 25591168
TI  - Cooperative surveillance and pursuit using unmanned aerial vehicles and
      unattended ground sensors.
AB  - This paper considers the problem of path planning for a team of unmanned aerial
      vehicles performing surveillance near a friendly base. The unmanned aerial
      vehicles do not possess sensors with automated target recognition capability and,
      thus, rely on communicating with unattended ground sensors placed on roads to
      detect and image potential intruders. The problem is motivated by persistent
      intelligence, surveillance, reconnaissance and base defense missions. The problem
      is formulated and shown to be intractable. A heuristic algorithm to coordinate
      the unmanned aerial vehicles during surveillance and pursuit is presented.
      Revisit deadlines are used to schedule the vehicles' paths nominally. The
      algorithm uses detections from the sensors to predict intruders' locations and
      selects the vehicles' paths by minimizing a linear combination of missed
      deadlines and the probability of not intercepting intruders. An analysis of the
      algorithm's completeness and complexity is then provided. The effectiveness of
      the heuristic is illustrated through simulations in a variety of scenarios. 

PMID- 25591169
TI  - Ferrocene-functionalized 4-(2,5-Di(thiophen-2-yl)-1H-pyrrol-1-yl)aniline: a novel
      design in conducting polymer-based electrochemical biosensors.
AB  - Herein, we report a novel ferrocenyldithiophosphonate functional conducting
      polymer and its use as an immobilization matrix in amperometric biosensor
      applications. Initially, 4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1
      yl)amidoferrocenyldithiophosphonate was synthesized and copolymerized with 4-(2,5
      di(thiophen-2-yl)-1H-pyrrol-1-yl)benzenamine at graphite electrodes. The amino
      groups on the polymer were utilized for covalent attachment of the enzyme glucose
      oxidase. Besides, ferrocene on the backbone was used as a redox mediator during
      the electrochemical measurements. Prior to the analytical characterization,
      optimization studies were carried out. The changes in current signals at +0.45 V
      were proportional to glucose concentration from 0.5 to 5.0 mM. Finally, the
      resulting biosensor was applied for glucose analysis in real samples and the data
      were compared with the spectrophotometric Trinder method. 

PMID- 25591167
TI  - Genetic diversity of avian influenza A (H10N8) virus in live poultry markets and
      its association with human infections in China.
AB  - Following the first human infection with the influenza A (H10N8) virus in
      Nanchang, China in December 2013, we identified two additional patients on
      January 19 and February 9, 2014. The epidemiologic, clinical, and virological
      data from the patients and the environmental specimen collected from 23 local
      live poultry markets (LPMs) were analyzed. The three H10N8 cases had a history of
      poultry exposure and presented with high fever (>38 degrees C), rapidly
      progressive pneumonia and lymphopenia. Substantial high levels of cytokines and
      chemokines were observed. The sequences from an isolate
      (A/Environment/Jiangxi/03489/2013 [H10N8]) in an epidemiologically linked LPM
      showed highly identity with human H10N8 virus, evidencing LPM as the source of
      human infection. The HA and NA of human and environmental H10N8 isolates showed
      high identity (99.1-99.9%) while six genotypes with internal genes derived from
      H9N2, H7N3 and H7N9 subtype viruses were detected in environmental H10N8
      isolates. The genotype of the virus causing human infection, Jiangxi/346,
      possessed a whole internal gene set of the A/Environment/Jiangxi/10618/2014(H9N2)
      like virus. Thus, our findings support the notion that LPMs can act as both a
      gene pool for the generation of novel reassortants and a source for human
      infection, and intensive surveillance and management should therefore be
      conducted. 

PMID- 25591170
TI  - Physico-mathematical simulation of a homogeneous thermal field of multichannel
      raster matrixes for sensors of oxygen.
AB  - In the paper, an opportunity for the development of multichannel transcutaneous
      raster matrixes for sensors of oxygen on the basis of an electrochemical cell
      sensor is described. An analysis of the influence of heat sources on the
      distribution of the temperature pattern of a raster matrix for sensors of oxygen
      had been carried out, and their optimum configuration had been found. The
      application of such matrixes will enable one to obtain information about the
      distribution of the partial pressure of oxygen from the skin cover of the object
      of research in dynamics, to assess its functional health pattern in a more
      comprehensive way and to control the effect of possible remedial actions. 

PMID- 25591171
TI  - Co3O4@MWCNT nanocable as cathode with superior electrochemical performance for
      supercapacitors.
AB  - Using a simple hydrothermal procedure, cobalt oxide (Co3O4) with preferred
      orientation along (220) planes is in situ prepared and coated on MWCNT. The
      prepared Co3O4@MWCNT nanocable shows superior electrochemical performance as
      cathode material for aqueous supercapacitors in 0.5 M KOH solution. Its redox
      peaks retain the well-defined shapes even when the scan rate increases to 200
      mV/s. Its specific capacitance is high, 590 F/g at 15 A/g and 510 F/g even at 100
      A/g within the potential range from -0.2 to 0.58 V (vs SCE). There is no
      capacitance fading after 2000 full cycles. This excellent performance is superior
      to the pristine and the reported Co3O4, which is ascribed to the unique nanocable
      structure with orientation. 

PMID- 25591172
TI  - Alternative method for intramuscular fat analysis using common laboratory
      equipment.
AB  - A procedure to quantify intramuscular fat was developed using common inexpensive
      laboratory equipment. Three homogenization methods of lyophilized muscle samples
      (Ball-mill, Grinder and Mortar) and two extraction methods (Ball-mill or Vortex)
      were used in turkey meat and pork. Two-hundred mg of lyophilized and homogenized
      samples were accurately weighed and mixed with 1.5 mL of dichloromethane-methanol
      (8:2) and shaken either in a Mixer Mill (MM400, Retsch Technology) or in a
      Vortex. The final mixture was separated by centrifugation. Solvent was evaporated
      under a nitrogen stream and lipid content was gravimetrically determined.
      Besides, it was checked that the fatty acid profile was not altered by the
      protocol used. Moreover, the analysis of 4 replicas from the same sample showed
      different variation coefficients (16-29%) for the new procedures proposed over a
      wide range of IMF content. The combination of Grinder and Vortex methodologies
      can be proposed as a simple and inexpensive alternative to previous ones.

PMID- 25591173
TI  - Strain-specific interaction of a GII.10 Norovirus with HBGAs.
AB  - Noroviruses (NoVs), an important cause of gastroenteritis in humans, recognize
      human histo-blood group antigens (HBGAs) as receptors. The crystal structures of
      the protruding (P) domain of a GII.10 NoV (Vietnam 026) in complex with various
      HBGA oligosaccharides were elucidated. However, the HBGA binding profile of this
      virus remains unknown. In this study, we determined the saliva and
      oligosaccharide binding profiles of this virus and the roles of amino acids that
      are involved in HBGA binding. Our data showed that Vietnam 026 bound to all ABO
      secretor and non-secretor saliva with clear signals detected by monoclonal
      antibodies against H3, H1, Le(y), Le(a) and sialyl Le(a). Mutagenesis study
      confirmed the binding site determined by the crystallography study, in which
      single mutations wiped out the binding function. We also identified amino acids
      surrounding the central binding pocket that may participate in the binding by
      affecting the HBGA binding specificity of the GII.10 NoV. 

PMID- 25591174
TI  - Pathogenesis of Soybean mosaic virus in soybean carrying Rsv1 gene is associated
      with miRNA and siRNA pathways, and breakdown of AGO1 homeostasis.
AB  - Profiling small RNAs in soybean Williams 82 (rsv), susceptible to Soybean mosaic
      virus (SMV, the genus Potyvirus, family Potyviridae) strains G2 and G7, and
      soybean PI96983 (Rsv1), resistant to G2 but susceptible to G7, identified the
      microRNA miR168 that was highly overexpressed only in G7-infected PI96983 showing
      a lethal systemic hypersensitive response (LSHR). Overexpression of miR168 was in
      parallel with the high-level expression of AGO1 mRNA, high-level accumulation of
      miR168-mediated AGO1 mRNA cleavage products but with severely repressed AGO1
      protein. In contrast, AGO1 mRNA, degradation products and protein remained
      without significant changes in G2- and G7-infected Williams 82. Moreover, knock
      down of SGS3, an essential component in RNA silencing, suppressed AGO1 siRNA,
      partially recovered repressed AGO1 protein, and alleviated LSHR severity in G7
      infected Rsv1 soybean. These results suggest that both miRNA and siRNA pathways
      are involved in G7 infection of Rsv1 soybean, and LSHR is associated with
      breakdown of AGO1 homeostasis. 

PMID- 25591176
TI  - Cytorhabdovirus phosphoprotein shows RNA silencing suppressor activity in plants,
      but not in insect cells.
AB  - RNA silencing in plants and insects provides an antiviral defense and as a
      countermeasure most viruses encode RNA silencing suppressors (RSS). For the
      family Rhabdoviridae, no detailed functional RSS studies have been reported in
      plant hosts and insect vectors. In agroinfiltrated Nicotiana benthamiana leaves
      we show for the first time for a cytorhabdovirus, lettuce necrotic yellows virus
      (LNYV), that one of the nucleocapsid core proteins, phosphoprotein (P) has
      relatively weak local RSS activity and delays systemic silencing of a GFP
      reporter. Analysis of GFP small RNAs indicated that the P protein did not prevent
      siRNA accumulation. To explore RSS activity in insects, we used a Flock House
      virus replicon system in Drosophila S2 cells. In contrast to the plant host, LNYV
      P protein did not exhibit RSS activity in the insect cells. Taken together our
      results suggest that P protein may target plant-specific components of RNA
      silencing post siRNA biogenesis. 

PMID- 25591175
TI  - Antigenic requirement for Gag in a vaccine that protects against high-dose
      mucosal challenge with simian immunodeficiency virus.
AB  - We reported previously on a vaccine approach that conferred apparent sterilizing
      immunity to SIVsmE660. The vaccine regimen employed a prime-boost using vectors
      based on recombinant vesicular stomatitis virus (VSV) and an alphavirus replicon
      expressing either SIV Gag or SIV Env. In the current study, we tested the ability
      of vectors expressing only the SIVsmE660 Env protein to protect macaques against
      the same high-dose mucosal challenge. Animals developed neutralizing antibody
      levels comparable to or greater than seen in the previous vaccine study. When the
      vaccinated animals were challenged with the same high-dose of SIVsmE660, all
      became infected. While average peak viral loads in animals were slightly lower
      than those of previous controls, the viral set points were not significantly
      different. These data indicate that Gag, or the combination of Gag and Env are
      required for the generation of apparent sterilizing immunity to the SIVsmE660
      challenge. 

PMID- 25591177
TI  - Evaluation of injectable strontium-containing borate bioactive glass cement with
      enhanced osteogenic capacity in a critical-sized rabbit femoral condyle defect
      model.
AB  - The development of a new generation of injectable bone cements that are bioactive
      and have enhanced osteogenic capacity for rapid osseointegration is receiving
      considerable interest. In this study, a novel injectable cement (designated Sr
      BBG) composed of strontium-doped borate bioactive glass particles and a chitosan
      based bonding phase was prepared and evaluated in vitro and in vivo. The
      bioactive glass provided the benefits of bioactivity, conversion to
      hydroxyapatite, and the ability to stimulate osteogenesis, while the chitosan
      provided a cohesive biocompatible and biodegradable bonding phase. The Sr-BBG
      cement showed the ability to set in situ (initial setting time = 11.6 +/- 1.2
      min) and a compressive strength of 19 +/- 1 MPa. The Sr-BBG cement enhanced the
      proliferation and osteogenic differentiation of human bone marrow-derived
      mesenchymal stem cells in vitro when compared to a similar cement (BBG) composed
      of chitosan-bonded borate bioactive glass particles without Sr. Microcomputed
      tomography and histology of critical-sized rabbit femoral condyle defects
      implanted with the cements showed the osteogenic capacity of the Sr-BBG cement.
      New bone was observed at different distances from the Sr-BBG implants within
      eight weeks. The bone-implant contact index was significantly higher for the Sr
      BBG implant than it was for the BBG implant. Together, the results indicate that
      this Sr-BBG cement is a promising implant for healing irregularly shaped bone
      defects using minimally invasive surgery. 

PMID- 25591179
TI  - Pharmacologic options for the treatment of chronic daily headache.

PMID- 25591180
TI  - Correction. Delirium in Older Persons: Evaluation and Management.

PMID- 25591178
TI  - Composition, formation, and regulation of the cytosolic c-ring, a dynamic
      component of the type III secretion injectisome.
AB  - Many gram-negative pathogens employ a type III secretion injectisome to
      translocate effector proteins into eukaryotic host cells. While the structure of
      the distal "needle complex" is well documented, the composition and role of the
      functionally important cytosolic complex remain less well understood. Using
      functional fluorescent fusions, we found that the C-ring, an essential and
      conserved cytosolic component of the system, is composed of ~22 copies of SctQ
      (YscQ in Yersinia enterocolitica), which require the presence of YscQC, the
      product of an internal translation initiation site in yscQ, for their cooperative
      assembly. Photoactivated localization microscopy (PALM) reveals that in vivo,
      YscQ is present in both a free-moving cytosolic and a stable injectisome-bound
      state. Notably, fluorescence recovery after photobleaching (FRAP) shows that YscQ
      exchanges between the injectisome and the cytosol, with a t1/2 of 68 +/- 8
      seconds when injectisomes are secreting. In contrast, the secretin SctC (YscC)
      and the major export apparatus component SctV (YscV) display minimal exchange.
      Under non-secreting conditions, the exchange rate of YscQ is reduced to t1/2 =
      134 +/- 16 seconds, revealing a correlation between C-ring exchange and
      injectisome activity, which indicates a possible role for C-ring stability in
      regulation of type III secretion. The stabilization of the C-ring depends on the
      presence of the functional ATPase SctN (YscN). These data provide new insights
      into the formation and composition of the injectisome and present a novel aspect
      of type III secretion, the exchange of C-ring subunits, which is regulated with
      respect to secretion. 

PMID- 25591182
TI  - The health consequences of adverse childhood experiences: role of the family
      physician.

PMID- 25591183
TI  - Diagnosis, treatment, and prevention of gout.
AB  - Gout is characterized by painful joint inflammation, most commonly in the first
      metatarsophalangeal joint, resulting from precipitation of monosodium urate
      crystals in a joint space. Gout is typically diagnosed using clinical criteria
      from the American College of Rheumatology. Diagnosis may be confirmed by
      identification of monosodium urate crystals in synovial fluid of the affected
      joint. Acute gout may be treated with nonsteroidal anti-inflammatory drugs,
      corticosteroids, or colchicine. To reduce the likelihood of recurrent flares,
      patients should limit their consumption of certain purine-rich foods (e.g., organ
      meats, shellfish) and avoid alcoholic drinks (especially beer) and beverages
      sweetened with high-fructose corn syrup. Consumption of vegetables and low-fat or
      nonfat dairy products should be encouraged. The use of loop and thiazide
      diuretics can increase uric acid levels, whereas the use of the angiotensin
      receptor blocker losartan increases urinary excretion of uric acid. Reduction of
      uric acid levels is key to avoiding gout flares. Allopurinol and febuxostat are
      first-line medications for the prevention of recurrent gout, and colchicine
      and/or probenecid are reserved for patients who cannot tolerate first-line agents
      or in whom first-line agents are ineffective. Patients receiving urate-lowering
      medications should be treated concurrently with nonsteroidal anti-inflammatory
      drugs, colchicine, or low-dose corticosteroids to prevent flares. Treatment
      should continue for at least three months after uric acid levels fall below the
      target goal in those without tophi, and for six months in those with a history of
      tophi. 

PMID- 25591184
TI  - Common questions about developmental dysplasia of the hip.
AB  - Developmental dysplasia of the hip is a common musculoskeletal condition in
      newborns. Infants with developmental dysplasia of the hip, whether treated or
      untreated, have a higher incidence of early-onset hip osteoarthritis in
      adulthood. Evidence to support universal screening by physical examination or
      ultrasonography is limited and often conflicting. The U.S. Preventive Services
      Task Force found insufficient evidence that screening for developmental dysplasia
      of the hip prevents adverse outcomes. Physical examination screening is
      recommended by the American Academy of Pediatrics and the Pediatric Orthopaedic
      Society of North America. These organizations recommend use of the Ortolani and
      Barlow maneuvers to screen infants up to three months of age. Several recent
      studies support starting assessment for limited hip abduction at eight weeks of
      age, which is the most sensitive test for developmental dysplasia of the hip from
      this age on. Infants with overtly dislocated or dislocatable hips should be
      referred to an orthopedist on a priority basis at the time of diagnosis. Infants
      with equivocal hip examination findings at birth can be reexamined in two weeks.
      If there is subluxation or dislocation at the follow-up examination, referral
      should be made at that time. If the examination findings are still equivocal, the
      infant can undergo ultrasonography of the hips or be reexamined every few weeks
      through the first six weeks of life. Although equivocal findings commonly resolve
      spontaneously, infants with persistent equivocal findings of developmental
      dysplasia of the hip longer than six weeks should be evaluated by an orthopedist.
      Treatment generally involves flexion-abduction splinting. The benefits of
      treatment are unclear, and there are risks to treatment, most notably an
      increased occurrence of avascular necrosis of the femoral head. 

PMID- 25591185
TI  - Role of the family physician in the care of children with Down syndrome.
AB  - Down syndrome is the most common chromosomal abnormality, occurring in one in 691
      live births in the United States each year. Prenatally, the sequential contingent
      test for aneuploidy screening is highly sensitive for Down syndrome and has a low
      false-positive rate. The diagnosis should be confirmed with fluorescent in situ
      hybridization followed by chromosomal karyotyping at birth. Children with Down
      syndrome have varied degrees of intellectual disability and more health
      complications than other children. However, advancements in recent decades have
      led to improved life expectancy, satisfaction, and quality of life. Newborns with
      Down syndrome require echocardiography and cardiology evaluation. Children should
      have annual screenings for vision and hearing, and laboratory studies for
      subclinical thyroid disease and blood disorders. Clinicians should provide
      unbiased and comprehensive culturally sensitive information regarding available
      services for children with Down syndrome. There is good evidence that
      comprehensive early intervention programs (e.g., speech, visual, physical, and
      occupational therapy; child psychology) enhance development. It is important to
      enroll children with Down syndrome in state-specific resources as early as
      possible. Given the advances in medical care and early intervention programs,
      regular health supervision by family physicians can allow children with Down
      syndrome to lead healthy and productive lives. 

PMID- 25591186
TI  - Peripheral artery disease screening and cardiovascular disease risk assessment
      with the ankle-brachial index in adults.

PMID- 25591187
TI  - Abnormal electrocardiogram findings during an occupational physical examination.

PMID- 25591191
TI  - Patient Information. Developmental dysplasia of the hip.

PMID- 25591192
TI  - Patient Information. Caring for your baby with Down syndrome.

PMID- 25591194
TI  - Getting medicine right: overcoming the problem of overscreening, overdiagnosis,
      and overtreatment.

PMID- 25591195
TI  - Improving quality by doing less: overscreening.

PMID- 25591196
TI  - Methotrexate therapy for rheumatoid arthritis.

PMID- 25591197
TI  - Zinc supplementation in children six months to 12 years of age.

PMID- 25591198
TI  - Surveillance of the adult cancer survivor.
AB  - The term "cancer survivor" refers to anyone living with a diagnosis of cancer. As
      the U.S. population ages, cancer screening increases, and cancer treatments
      improve, millions more Americans will be classified as cancer survivors in the
      future. Although many survivors wish to continue care with their oncologists,
      patients benefit from care provided by a family physician. Many survivors are
      older and have comorbidities, which should be addressed to optimize function and
      longevity. Common late effects of cancer and its treatment include second primary
      cancers, sexual dysfunction, and psychosocial issues. Cancer recurrence is a
      significant concern. After treatment for colorectal cancer, intensive
      surveillance, including colonoscopy, imaging, and serology, confers an overall
      survival benefit. Breast cancer survivors should receive annual mammography.
      Prostate cancer survivors should undergo prostate-specific antigen testing every
      six to 12 months. Melanoma survivors should be counseled on sun protection,
      including daily sunscreen use, and recognizing characteristics of potentially
      malignant skin lesions. Female survivors of Hodgkin lymphoma who were treated
      with chest or axillary radiation between 10 and 30 years of age are at high risk
      of breast cancer, and should be screened with mammography and magnetic resonance
      imaging annually starting eight to 10 years after the diagnosis. All cancer
      survivors treated with chest radiation are at increased risk of cardiovascular
      disease, and should be screened for other cardiovascular risk factors and treated
      as indicated. 

PMID- 25591199
TI  - Recognition and management of motor delay and muscle weakness in children.
AB  - Diagnosis of neuromuscular disorders in young children is often delayed for years
      after symptoms emerge, resulting in missed opportunities for therapy and genetic
      counseling. Identification of the weak child begins with careful attention to
      caregiver concerns and developmental surveillance at well-child visits. Family
      and medical histories can differentiate inherited from acquired causes of
      weakness. Physical examination should include observation of ageappropriate motor
      skills such as pull-to-sit, sitting, rising to stand, and walking/running. Serum
      creatine kinase levels should always be measured in children exhibiting
      neuromuscular weakness. Referrals to early intervention programs should not be
      postponed pending definitive diagnosis. If motor delay does not improve with
      early intervention, referral to a pediatric neurologist for diagnostic assessment
      is recommended. Tongue fasciculations, loss of motor milestones, or creatine
      kinase level greater than three times the normal limit should prompt immediate
      neurology referral. Once a neuromuscular disorder is diagnosed, the primary care
      clinician can help the family navigate subspecialty visits and consultations,
      advocate for services in the school and home, and help them cope with the
      emotional stresses of caring for a child with special needs. 

PMID- 25591200
TI  - Initial evaluation, diagnosis, and treatment of anorexia nervosa and bulimia
      nervosa.
AB  - Eating disorders are life-threatening conditions that are challenging to address;
      however, the primary care setting provides an important opportunity for critical
      medical and psychosocial intervention. The recently published Diagnostic and
      Statistical Manual of Mental Disorders, 5th ed., includes updated diagnostic
      criteria for anorexia nervosa (e.g., elimination of amenorrhea as a diagnostic
      criterion) and for bulimia nervosa (e.g., criterion for frequency of binge
      episodes decreased to an average of once per week). In addition to the role of
      environmental triggers and societal expectations of body size and shape, research
      has suggested that genes and discrete biochemical signals contribute to the
      development of eating disorders. Anorexia nervosa and bulimia nervosa occur most
      often in adolescent females and are often accompanied by depression and other
      comorbid psychiatric disorders. For low-weight patients with anorexia nervosa,
      virtually all physiologic systems are affected, ranging from hypotension and
      osteopenia to life-threatening arrhythmias, often requiring emergent assessment
      and hospitalization for metabolic stabilization. In patients with frequent
      purging or laxative abuse, the presence of electrolyte abnormalities requires
      prompt intervention. Family-based treatment is helpful for adolescents with
      anorexia nervosa, whereas short-term psychotherapy, such as cognitive behavior
      therapy, is effective for most patients with bulimia nervosa. The use of
      psychotropic medications is limited for anorexia nervosa, whereas treatment
      studies have shown a benefit of antidepressant medications for patients with
      bulimia nervosa. Treatment is most effective when it includes a
      multidisciplinary, teambased approach. 

PMID- 25591201
TI  - Swelling of the lips.

PMID- 25591203
TI  - Opting out of medicaid expansion may cost States additional primary care
      physicians.

PMID- 25591205
TI  - Page for Patients. Eating disorders: what you should know.

PMID- 25591207
TI  - More than a rash: skin disease and quality of life.

PMID- 25591208
TI  - Screening and surveillance for colorectal cancer: avoiding the pitfalls of
      overscreening.

PMID- 25591209
TI  - Common questions about wound care.
AB  - Lacerations, abrasions, burns, and puncture wounds are common in the outpatient
      setting. Because wounds can quickly become infected, the most important aspect of
      treating a minor wound is irrigation and cleaning. There is no evidence that
      antiseptic irrigation is superior to sterile saline or tap water. Occlusion of
      the wound is key to preventing contamination. Suturing, if required, can be
      completed up to 24 hours after the trauma occurs, depending on the wound site.
      Tissue adhesives are equally effective for low-tension wounds with linear edges
      that can be evenly approximated. Although patients are often instructed to keep
      their wounds covered and dry after suturing, they can get wet within the first 24
      to 48 hours without increasing the risk of infection. There is no evidence that
      prophylactic antibiotics improve outcomes for most simple wounds. Tetanus toxoid
      should be administered as soon as possible to patients who have not received a
      booster in the past 10 years. Superficial mild wound infections can be treated
      with topical agents, whereas deeper mild and moderate infections should be
      treated with oral antibiotics. Most severe infections, and moderate infections in
      high-risk patients, require initial parenteral antibiotics. Severe burns and
      wounds that cover large areas of the body or involve the face, joints, bone,
      tendons, or nerves should generally be referred to wound care specialists. 

PMID- 25591210
TI  - Colorectal cancer screening and surveillance.
AB  - Colorectal cancer is the third most common cancer in men and women. The incidence
      and mortality rate of the disease have been declining over the past two decades
      because of early detection and treatment. Screening in persons at average risk
      should begin at 50 years of age; the U.S. Preventive Services Task Force
      recommends against routine screening after 75 years of age. Options for screening
      include high-sensitivity fecal occult blood testing annually, flexible
      sigmoidoscopy every five years with high-sensitivity fecal occult blood testing
      every three years, or colonoscopy every 10 years. In 2012, the U.S. Multi-Society
      Task Force on Colorectal Cancer updated its surveillance guidelines to promote
      the appropriate use of colonoscopy resources and reduce harms from delayed or
      unnecessary procedures; these guidelines provide recommendations for when to
      repeat colonoscopy based on findings. Adenomatous and serrated polyps have
      malignant potential and warrant early surveillance colonoscopy. Patients with one
      or two tubular adenomas that are smaller than 10 mm should have a repeat
      colonoscopy in five to 10 years. Repeat colonoscopy at five years is recommended
      for patients with nondysplastic serrated polyps that are smaller than 10 mm.
      Patients with three to 10 adenomas found during a single colonoscopy, an adenoma
      or serrated polyp that is 10 mm or larger, an adenoma with villous features or
      high-grade dysplasia, a sessile serrated polyp with cytologic dysplasia, or a
      traditional serrated adenoma are at increased risk of developing advanced
      neoplasia during surveillance and should have a repeat colonoscopy in three
      years. More than 10 synchronous adenomas warrant surveillance colonoscopy in less
      than three years. Colonoscopy may be repeated in 10 years if distal, small (less
      than 10 mm) hyperplastic polyps are the only finding. 

PMID- 25591211
TI  - Disability evaluations: more than completing a form.
AB  - According to the World Health Organization, more than 1 billion persons worldwide
      have a disability. In the United States, more than 56 million American workers
      have some form of disability; of these, more than 38 million persons have a
      severe disability. Blacks and Hispanics are among the groups with the highest
      disability rates, as well as older patients. Conditions that most often lead to
      disability include arthritis, back or spine problems, and heart conditions.
      Common limitations include the inability to walk three city blocks or to climb a
      flight of stairs. Patients with a disability experience health disparities and
      barriers to appropriate health care. Disability impacts family members and
      caregivers, as well as patients. Impairment, disability, and handicap are key
      terms that physicians must understand to properly evaluate patients and make
      appropriate recommendations. Social Security Disability Insurance and workers'
      compensation are the two largest disability programs in the United States. The
      U.S. Department of Veterans Affairs provides disability benefits for veterans,
      and private disability insurance may be provided by the employer or purchased by
      the employee. Family physicians can perform the initial evaluation, consult
      appropriate subspecialists, complete the necessary paperwork, and answer
      questions from the patient, employer, or disability agency. 

PMID- 25591213
TI  - Medications for treatment of interstitial cystitis.

PMID- 25591214
TI  - Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer
      in Women.

PMID- 25591215
TI  - Skin sloughing and lip lesions after a recent foot procedure.

PMID- 25591216
TI  - Screening for hereditary cancer syndromes.

PMID- 25591222
TI  - Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer
      in Women: Recommendation Statement.

PMID- 25591223
TI  - Colon cancer screening: what you should know.

PMID- 25591224
TI  - Wound care.

PMID- 25591225
TI  - Patient portals: the good, the bad, and the inevitable.

PMID- 25591226
TI  - Chronic Care Management and Other New CPT Codes.

PMID- 25591227
TI  - EHR Switch Survey: Responses From 305 Family Physicians.

PMID- 25591228
TI  - Digesting the ICD-10 GI Codes.

PMID- 25591229
TI  - Removing six key barriers to online portal use.

PMID- 25591234
TI  - VisualDx.

PMID- 25591239
TI  - Knowledge is not enough.

PMID- 25591240
TI  - Technology in performing arts healthcare research.

PMID- 25591241
TI  - Withdrawn: Misuse of Tri-solfen in cattle is a concern for export industry.

PMID- 25591242
TI  - [Epidemiology of chronic bronchopulmonary disease].

PMID- 25591243
TI  - [Allergenic pollutants and their influence upon the human organism].

PMID- 25591244
TI  - [The concept of mental health in the option of psychiatric attendance].

PMID- 25591245
TI  - [Amyloid disorder].

PMID- 25591246
TI  - [Betalactamase inhibitors].

PMID- 25591247
TI  - [Clinic and pathogenesis of drug hepatitis].

PMID- 25591248
TI  - [Hypophysary and ovarian anatomopathological alterations in menopause].
AB  - A simultaneous hystopatological investigation of hypophysis and ovary in 80 women
      aged between 48 and 60 years was carried out. The obtained data pointed out that
      about menopause the hypophysis increases its activity and the ovaries present
      important pIenomena of sclerosis which could be determined by the hypersecretion
      of gonadotropic hormones. The decrease in sensitivity of the hormone-sensitive
      areas to the negative feed-back of estrogens would contribute to the setting up
      of the hypothalamic hypertonia on gonadotropic axis. The hypothesis is suggested,
      on one hand, by the fact that the degenerative ovarian insufficiency and the
      ovarian vascular alterations in menopause represent singular phenomena in the
      constellation of all the other endocrine glands and, on the other hand, by the
      fact that hypophysis, in menopause, increases its activity.

PMID- 25591249
TI  - [Corticotherapy in aggressive chronic hepatitis (ACH)].
AB  - 48 patients with the diagnosis of ACH, admitted in the interval 1972-1981 and
      subjuected to corticotherapy were investigated by hepatic puncture biopsy with
      Vim-Silverman needls. The dose of prednison was of 15-20 mg daily for 2-4 years,
      with a mean 20 months. Corticotherapy was efficient in 73% of the cases,
      stabilization of the clinical and hepatic functional pictures being obtained. In
      17% of the cases the hepatic process persited unmodified and in 10% ACH evolved
      towards cirrhosis.

PMID- 25591250
TI  - [Differences concerning some immunological markers in viral hepatitis A and B].
AB  - From the carried out investigations it results that in the acute period hepatitis
      A and B has an evolution with immunological alterations different in intensity
      and direction. In hepatitis B a more lasting immune reorganization was pointed
      out, at the basis of which are, possibly, autoimmune processes which are
      instituted even at the onset of the disease and which are subsequently
      conditioning the chronic affecting of the liver.

PMID- 25591251
TI  - [Studies regarding the chronicization potential of viral hepatitis in children].
AB  - Out of 205 children, former patients with viral hepatitis, investigated after the
      end of the follow-up period by clinical and laboratory examinations, 9 (4.4%)
      presented mild or moderate pathological alterations. At the second control,
      carried out after an another interval de 1-11/2 years, the pathological
      alterations were refound only in 2 of the former patients, suggesting that all
      the others presented lasting forms of acute viral hepatitis evolving towards
      healing. The presence of AgHBs and the alteration of proteinogramme in the acute
      phase of VH can serve as criteria of unfavourable prognosis of the disease
      evolution and impose a preferential follow-up of this category of patients.

PMID- 25591252
TI  - [Convulsive syndrome in infantile shigellosis].
AB  - Infantile shigellosis determines convulsions almost 5 times more frequently than
      the diarrheas of other etiology, the hyperpyrexy favouring significantly its
      release, on the background of a genetic disturbance and cerebral hypoxic
      mechanism.

PMID- 25591253
TI  - [Medical and socio-economical significance of rehabilitation of the patients with
      late postinfectious articular rheumatism].
AB  - As part of a clinical-epidemiological follow-up carried out between 1975 and 1979
      in Iasi, the evolution of the clinical and functional recuperatory process in a
      series of 269 patients with articular rheumatismal manifestations, out of which
      67.6% caused by pharyngo-amigdalytis infections, was studied. The investigations
      on ASLO, fibrinogen, VSH, urinary sediment, ECG and presence of some germs,
      having etiological significance, in the nasopharyngeal exudate have brought data
      pleading for the infectious-allergic etiopathogenesis of an important number of
      the chronic articular rheumatism cases. The drug treatment and
      balneophysiotherapy had full recuperatory effects in 18.2% and partial ones in
      57.6% of the cases. The cost of the recuperatory intervention is about 4-4,500
      lei/year/patient.

PMID- 25591254
TI  - [Mediastinal tumours and cysts].
AB  - On 650 intrathoracic surgical interventions performed in the Ist Clinic of
      Surgery in Iasi, 66 mediastinal tumours and cysts, interesting due to their
      variety, diagnosis and treatment problems, were recorded: 14 tumours of nervous
      origin, 21 mediastinal goitres, 5 dermoid cysts, 4 thymomas, 5 serous celomic
      cysts, 3 lipomas, 3 hydatic cysts, 4 lymphosarcomas, 3 osteochondromas, 3
      pseudotumoral adenopathies, 1 pleural fibroma. In the case of a mediastinal
      tumour the routine intervention was explorative thoracotomy followed by exeresis
      of the tumour, establishment of the diagnosis and, at the same time, favourably
      working out the cases without postoperative morbidity and mortality.

PMID- 25591255
TI  - [Essential trigeminal neuralgia].
AB  - Out of a series of 364 patients, 56 cases of essential trigeminal neuralgias
      operated upon by retrogasserian radicotomy by intradural temporal route are
      presented. Pointing out that we are in a period of confrontation between the
      great surgery, classical or micro-neurosurgery of the trigeminal nerve and the
      drug therapy or percutaneous surgery, the authors conclude that the indication of
      great surgery is restricted but has not disappeared--taking into account the good
      permanent results obtained (89%) and the reduced rate of failures and recurrences
      (11%). In the conditions of a general anesthesia with intracranial hypotension
      and correct surveillance the surgeon has gaine an extra security when performing
      these operations.

PMID- 25591256
TI  - [The place of osteosynthesis with screwed up metallic plates in the treatment of
      the shaft fractures of the forearm bones].
AB  - The modern findings regarding the biomechanics of the forearm call for an as
      perfect as possible reduction of the fractures at this level. That is why,
      especially in adults, the surgical treatment is gaining more and more ground. In
      this context the osteosynthesis with screwed up metallic plates, preferably with
      compression, any time the local situation allows, it, represents the method of
      choice. In the 333 cases operated upon during 1971-1980 it has offered us full
      satisfaction. The taping with Kuntscher nail was indicated--especially in the
      past--only in some fractures of ulna, mainly in the oblique ones, in which the
      rod is blocking more easily the rotary motions.

PMID- 25591257
TI  - [Chronic obstructive bronchopneumopathy, pulmonary cancer and tuberculosis.
      Trends and different approaches of the health programmes].
AB  - This paper represents a comparative analysis of the main pulmonary chronic
      diseases (COBP, cancer, tuberculosis) in regard of morbidity, mortality,
      temporary disablement, invalidity, medical and economic expenses, the way of
      providing medical attendance and their share in the health programmes of our
      country. The authors point out the fact that, in the present health programmes,
      pulmonary tuberculosis and bronchopulmonary cancer benefit by proper priorities
      as against their gravity, while COBP is not mentioned in these programmes
      although it surpasses the medical and socio-economic implications of the other
      two diseases. In conclusion the authors consider that the phthisiological
      departments (in the conditions of the permanent decrease of morbidity and
      mortality by tuberculosis) dispose of technical competency, medical equipment and
      allowances sufficient for starting the coordination of the actions of prevention,
      reduction, diagnosis, treatment and recovery of the COBP patients.

PMID- 25591258
TI  - [Evolution of endemic tuberculosis in the Iasi District: between 1972 and 1980].
AB  - Continuing our longitudinal study on the evolution of the tuberculosis endemic in
      the Iasi district, the epidemiometric indicators recorded between 1972 and 1980
      were estimated. It was noticed that the epidemiological state of tuberculosis has
      improved considerably. The instantaneous prevalence of the bacillary patients
      decreased with 72% and the maximum one with 66.4%. The limitation of the
      contagion sources was reflected on the prevalence of tuberculosis in children,
      which decreased in the same period with 87.2%. The epidemiological process
      regressed slowly in the adult population, while in children it regressed rapidly
      and substantially.

PMID- 25591259
TI  - [Evolution of the sensitivity to cloramphenicol of Salmonela typhi strains
      isolated in the last 20 years in Moldova (Romania)].
AB  - The antibiogram of 658 S. typhi strains isolated in Moldova during the last 20
      years points out that this bacterium is preserving in the studied area its
      natural sensitivity towards the antibiotics used in the treatment of typhoid
      fever. A very small number of strains resistant to these antibiotics (below 0.5%)
      have appeared as an accident without clinico-epidemiological consequences. The
      MIC unimodal distribution of cloramphenicol and other antibiotics towards S.
      typhi is similar to the MIC distribution towards the serotypes with very limited
      circulation (S. java) and much different from the MIC bimodal distribution
      towards the serotypes having a wide circulation (S. agona). It is considered that
      the cause of the relative protection of S. typhi strains in Moldova (as a matter
      of fact in all the country) from the resistance plasmides was only the ever
      limited circulation of this species. It is opted for the necessity of a
      surveillance by antibiogramm of the circulating S. typhi strains.

PMID- 25591260
TI  - [Epidemiological investigations among the viral hepatitis contact in a close
      children collectivity].
AB  - The results of the clinico-epidemiological and laboratory (TGP, tymol and HBsAg)
      investigations carried out in 164 contacts of an icteric case of viral hepatitis
      from a creche type children collectivity are presented. A wide spread of the
      infection, expressed by subclinical forms of disease identified on the basis of
      the alterations of TGP and their dynamics (27.4%) was pointed out. The increased
      incidence of HBsAg carriers and the correlation with the TGP increased values
      allowed the conclusion that the infection was caused by the hepatitis virus type
      B. The epidemiological investigation established that the infection was
      transmitted by direct contact favoured by children's close physical contact.

PMID- 25591261
TI  - Potential mutagenic evaluation of the bentazone.

PMID- 25591262
TI  - [Statistic analysis of some risk factors in breast cancer].
AB  - We have tried to establish a possible connection between breast cancer and a
      series of individual factors: age of the menopause, woman's age at the first
      delivery, number of pregnancies and the number of born children, the age when the
      first symptom appeared (mammary tumor), environment, hereditary and collateral
      antecedents. The data have been analysed with the help of statistics methods and
      electronic computer programmes used to solve most complex problems. The
      conclusions regarding some risk factors, dependent on the statistic behaviour of
      the elements analysed, indicate a maximum frequency of the neoplasm incidence
      immediately after menopause, an increased risk for the aged primiparas and the
      protecting role of an early pregnancy, as well as a bimodal aspect of the
      frequency of this disease depending on the age at which the first symptom appears
      and the age of the menopause, with two maximums, the principal one placed within
      the first ten years after the setting in of menopause, and the second one
      occuring at about twenty years after menopause.

PMID- 25591263
TI  - [Changes in cellular transcription on terms of the type of proliferative stimulus
      in immune-reactive lymphocyte cultures].
AB  - Transcriptase activities were investigated in cell extracts of human circulating
      lymphocyte cultures stimulated for proliferation with polyclonal mitogens like
      PHA, PPD, and endotoxin from Salm. typhimurium S, and also with two
      polynucleotides. Enzymic activity of the cell extracts was tested
      differentiatelly for direct (DNA/RNA) and reverse (RNA/DNA) transcription, using
      appropriate template-primers: activated DAN and poly (dA). r(pU)10 for direct
      transcription, and poly (rA.rC. rU), poly (dA) x d(pT)10, and poly (rA). d(pT)12
      18 for reverse transcription. All lymphoproliferative stimulators are able to
      enhance simultaneously the cellular mitosis and the direct transcriptase activity
      in the cell. There is a good correlation between the two effects. Enzyme affinity
      to natural DNA is higher than to synthetic poly (dA) r(pU)10 PHA, a mitogen for T
      lymphocyte, enhances the eukaryote type of reverse transcriptase, while among the
      mitogens for B lymphocyte the PPD enhances an intermediate (viral-eukaryotic)
      type of reverse transcriptase, and ENDO is not stimulatory for reverse
      transcription. Duplex polyribonucleotides have an adjuvant activity: they
      intensify the action of stimulators but they have not a direct enhancing
      activity. The different transcriptases involved in the lymphocyte differentiation
      and proliferation may be targets for clinically useful immunosuppressive drugs
      differentiated for T and B cells.

PMID- 25591264
TI  - [Neurogenous digestive affections in the elderly].

PMID- 25591265
TI  - [Gastric and duodenal ulcer in the adults and elderly].
AB  - The gastric and duodenal ulcers in the elderly have an ever increasing incidence.
      The active follow-up, the dietary and drug treatment determine a decreased number
      of surgical interventions.

PMID- 25591266
TI  - [Methodological considerations regarding the applicative study of the dietary
      level and state of health indicators in the rural population].
AB  - The authors present their own experience on the methodology used for
      investigating the rural dietary phenomenon. The epidemiological investigations
      were qualitative-quantitative using a personally deviced card to which it was
      arrived after successive improvements. The aspects connected with the food
      consumption, criteria of choosing the unities of consumption, reference type and
      selection of the used clinical indicators are discussed.

PMID- 25591267
TI  - [Medical correlations between general patology and oral cavity].
AB  - The dento-maxillary system is, both in its development and in the maintainance of
      is integrity, in a close interdependence with the general state of the body, the
      deficitary enzymatic metabolic and immunologic alterations occuring during the
      evolution of some diseases concerning the general pathology. That fact implies
      the knowledge of the premorbid and morbid state of the entire body when
      establishing the diagnosis and the stomatologic therapy.

PMID- 25591268
TI  - [Phtalazinium lures (VIII). Action of p-nitrophenacyl bromide on phtalazine].
AB  - Continuing our investigations for obtaining stable diazinium-ylures, the
      conditions of obtaining and reactivity of p-nitrophenacyl-phtalazinium methylides
      were studied. This ylure leads by 3+2 dipolar cycloaddition with dimethyl
      acetylenedicarboxylate and N-phenyl-malein-ymide to the respective
      cycloadductions. The synthetized compounds were tested biologically.

PMID- 25591269
TI  - [Diazabicyclic systems (VII). Cycloaddition reactions of benzocinnoline via
      ylidic intermediates].
AB  - By the reaction of p-bromo-phenacyl bromide on the 3,8-dimethyl- and the 3,8-di
      methoxy-benzocinnoline, a cycloimmonium salts was obtained which, in the presence
      of triethylamine, was converted to benzocinnolinium-phenacylides. The existence
      in situ of the ylids was furnished evidence of the 3+2 dipolar cyclo- addition
      reactions with various dipolarophiles, such dimethyl and diethyl
      acetylenedicarboxylate, diethyl propiolate and also with diethyl
      azodicarboxylate. Thus, the application of the 1.3-dipolar additions is a
      successful route for the synthesis of some new bicyclic two nitrogen bridged
      systems.

PMID- 25591270
TI  - [Studies on the phytohormonal action of an extract prepared from Hippophae
      rhamnoides seeds (VII)].
AB  - Trying to test by 2 standard tests. AVENA and COLEUS, the stimulating capacity
      both of rhizogenesis and organogenesis under the influence of various concentrate
      doses obtained from extract of H. R. seeds together with M/10, M?20 and M/200
      dilutions of IAA (Indolil acetic acid) we could notice that the big
      concentrations of IAA and those of extract from H.R. lead to the tissues
      necrosis. The situation is different at to times diluted concentrations this
      being valid both for the sample and standard. The very small doses (corresponding
      to same M/200 dilutions) induce much too reduced effects for being
      macroscopically estimated. Based upon the results the authors believe that the
      extract prepared from 5 g of white sea buckthorn seeds corresponds to the
      intensity of action of 90 mg IAA but it is not entirely determined by the auxine
      existing in the seeds also by the potential of aminoacids found in a large
      quantity in this vegetable material.

PMID- 25591271
TI  - [Cardiac primitive amyloidosis].

PMID- 25591272
TI  - [The effort challenge tests in the diagnosis of ischemic cardiopathy].

PMID- 25591273
TI  - [Endemic thyroid disorders].

PMID- 25591274
TI  - [Practical test for competitive examination].

PMID- 25591275
TI  - [Half of a century of the Institute of Hygiene and Public Health of Iasi].

PMID- 25591276
TI  - [A century of teaching research and medico-legal assistance in Iasi].
AB  - On September 15, 1982, the Medico-Legal Department of the Institute of Medicine
      and Pharmacy of Iasi will celebrate one hundred years of activity reflected in
      the instruction of a great number of generations of physicians, forensic
      physicians and lawyers to say nothing of the remarkable services brought to the
      Courts of Law and public medical assistance in Moldavia. The organization of
      university and medical education in Iasi had to face implicitly the problem of
      teaching forensic medicine. This subject was tought for the first time in 1860 at
      the Faculty of Law of the "Al. I. Cuza" University of Iasi by I. Ciurea. He
      started teaching forensic medicine at the Faculty of Medicine in 1882. Professor
      I. Ciurea was specially sent abroad on the purpose of "studying medicine applied
      to Law". This stage of evolvement and development of the medico-legal studies in
      Iasi is associated today with the names of I. Ciurea, George Bogdan, Gr. T. Popa
      and N. Balan. Through their activity, publications and genuine scholarship they
      succeeded in founding a real scientific school of forensic medicine in Iasi. At
      the some time they asserted this subject both on the national and international
      level. An outstanding stage in the development of the forensic medicine in Iasi
      was its increasing application to questions of civil and 'criminal law,
      especially in court proceedings. This stage is brilliantly represented through
      the teaching, scientific activity and medico-legal assistance given by M.
      Kernbach. Nowadays we are actively implied in a new stage of development of the
      forensic studies. This is the period of the epistemological affirmation of the
      forensic medicine in Iasi. Its main task is the elaboration of epistemological
      models for the majority of the law questions which require the rigour of
      scientific truth. New discoveries have been made in keeping with the natural
      progress of forensic medicine in all its branches. Within the process of
      elaboration of new and more reliable criteria of judgement, all knowledge
      acquired was epistemologically systematized. The one hundred years of medico
      legal teaching at the Institute of Medicine and Pharmacy of Iasi signifies in
      fact more things at the same time: 170 years since the first medico-legal
      certificate had been emitted in Moldavia; 150 years since the first medico-legal
      autopsy; 118 years since the organization of the teaching of forensic medicine at
      the Faculty of Law; 91 years since I. Ciurea's death; 52 years since the death of
      G. Bogdan; and last but not least, 30 years since the organization of the system
      of medico-legal assistance in our socialist society. All these events, the
      remarkable achievements of the past, constitute an impetus to the prospective
      development of forensic medicine in Iasi, with the goal of obtaining an ever
      increasing coefficient of scientific accuracy of the medico-legal act as well as
      to the permanent contribution of forensic medicine to medical assistance and
      public sanity.

PMID- 25591277
TI  - The tangled web: a study of knowledge and attitude towards leprosy from a
      tertiary care hospital in India.
AB  - Leprosy stands tall among the oldest and most misunderstood diseases of man.
      Today leprosy is easily treated; unfortunately, persistent misconceptions result
      in unnecessary stigmatization. Thus the present study aims to assess the
      knowledge and attitudes regarding leprosy in people with and without leprosy,
      factors affecting the same; and to study their relationship with treatment status
      in leprosy patients. Detailed knowledge and attitude questionnaires were
      administered to 260 subjects (100 leprosy patients, 60 family members of leprosy
      patients and 100 people with non-leprosy skin diseases) at AIIMS, New Delhi.
      Crude scores based on subject responses were used for inter-group comparisons.
      Leprosy patients had significantly higher knowledge scores than family members
      who in turn scored significantly higher than people with other skin diseases.
      Leprosy patients had fair knowledge about common symptoms, but awareness about
      MDT was low. Delayed diagnosis and non-compliance were common. Attitudes did not
      differ between groups. Fear of the leprosy-affected and reluctance for physical
      contact, food sharing and marriage were prominent. Treated leprosy patients had
      the highest knowledge scores. Higher education and greater knowledge scores were
      positive predictors of attitude. Knowledge and attitude scores showed significant
      positive correlation. Knowledge and attitude towards leprosy are unsatisfactory.
      Improving knowledge may help to improve attitudes. In the post-elimination era,
      we must incorporate education about the disease into routine care of leprosy
      patients and focus on community education about leprosy.

PMID- 25591278
TI  - Selective Special Drive (SSD): an effective tool to promote new case detection
      through community participation--an experience during 2005-2010 in Mumbai slums.
AB  - As per the Guidelines of National Leprosy Eradication Programme (NLEP),
      Government of India, new case detection (NCD) in leprosy is to be promoted by
      voluntary reporting through Information, Education and Communication (IEC).
      Accordingly, in addition to the routine IEC activities, Maharashtra Lokahita Seva
      Mandal (MLSM) carried out Selective Special Drive (SSD) in slum pockets in Mumbai
      since 2005-06. The SSD methodology prescribed under Leprosy Elimination Action
      Program (LEAP) of ALERT-INDIA was adopted which included selection of slum
      pockets, identification and training of Community Volunteers (CVs), door-to-door
      focused IEC through CVs using standard IEC material and referral of voluntarily
      reported suspected cases to nearby Health Posts under General Health Services or
      to Leprosy Referral Centre (LRC) established through MLSM for diagnosis and
      treatment. During the years, 2005-06 to 2009-10, MLSM conducted five annual SSDs
      in 53 slum pockets having 187,391 house-holds with the total enumerated
      population of 882,114 of which 563,040 (63.8%) could be covered through house-to
      house IEC by 772 trained CVs/CHVs. As a result, 108 new cases (PB - 79 and MB -
      29) were detected with the NCD rate ranged between 13/100,000 and 34/100,000
      which is much higher than the reported NCDR in Mumbai (i.e. 6/100,000). Of the
      new MB cases 6 were lepromatous leprosy cases. Voluntary reporting of new cases
      was also found to be enhanced during the subsequent period following SSD. SSD
      activity encourages intensified IEC with community participation and integrates
      General Health Services resulting into better voluntary reporting of new cases.
      It is, therefore recommended that the SSD with the methodology prescribed under
      LEAP may be considered for incorporation in NLEP.

PMID- 25591279
TI  - Leprosy as a neglected disease and its stigma in the northeast of Brazil.
AB  - Hansen's disease is an infectious and degenerative chronic disease with a high
      potential for incapacitation. Due to the explosive epidemic of leprosy cases
      worldwide (especially in Brazil), the social difficulties faced by these patients
      are an important subject for research. This work aimed to identify the stigma
      experienced by these patients. The qualitative research for this study was
      completed at the National Reference Centre in Dermatology in Fortaleza. The study
      took place in northeast Brazil from September 2010 to November 2012. The research
      subjects included 20 people with Hansen's disease of both sexes between 20 and 70
      years old. The data collection consisted of a semi-structured interview. From the
      discourse analysis of the participants, several changes experienced by persons
      affected by leprosy were noted from the empiric categories emerged. Changes
      occurred in the family, the receptiveness of neighbours and co-workers and the
      patients' social lives were experienced by the persons affected after the
      diagnosis of Hansen's disease. From the data obtained, it was concluded that the
      patients are stigmatised. Sometimes they are forced to hide from relatives,
      friends, neighbours and co-workers. Despite their social exclusion, they believe
      their isolation is justified. Leprosy is a chronic, degenerative and curable
      infectious illness that continues to be a serious public health problem, mainly
      in the poorest region of Brazil.

PMID- 25591280
TI  - Lupus vulgaris: unusual presentation on face.
AB  - Lupus vulgaris is a variant of cutaneous tuberculosis. As the disease has
      potential to mutilate when left untreated, leaving deforming scars and
      disfigurement, an early diagnosis is of paramount importance. Though the common
      type is plaque type, rarely mutilating and vegetative forms also are found. A 28
      year old female, labourer presented with progressive annular plaque over right
      side of cheek extending upto right lower lid and ala of nose. There were two
      satellite plaques near the right side of giant lesion. On diascopy apple jelly
      nodule was seen. There was no regional lymhadenopathy. Histopathological
      examination showed many granulomas in upper dermis extending to deep dermis
      comprising of epitheloid cells with langhans' type of giant cells, lymphocytic
      infiltration & focal necrosis suggestive of lupus vulgaris. The consequences of
      failing to make an early diagnosis can be disastrous for the patients, as the
      progression of the disease can lead to necrosis, destruction of bones and
      cartilage leading to permanent deformity. Thus it is vital for clinicians to have
      a high index of suspicion of such atypical forms and take biopsy samples for
      histological and bacteriological studies.

PMID- 25591281
TI  - Leprosy interpreted as diabetes related complications.

PMID- 25591282
TI  - Collaborative care effective in cancer patients with depression.

PMID- 25591283
TI  - Have a high index of suspicion for atrial fibrillation.
AB  - The lifetime risk of atrial fibrillation (AF) for men and women over the age of
      40 is about 25%. The condition affects around 800,000 people in the UK, of which
      it is estimated that 250,000 are undiagnosed. A rapid heart rate may result in
      palpitations, dyspnoea or chest tightness, whereas loss of atrial contractility
      may lead to fatigue and reduced exercise capacity. There is a five-fold increased
      risk of ischaemic stroke, transient ischaemic attack or systemic embolism. AF
      strokes are larger, more disabling and have a higher mortality rate than those
      with other causes. The risk of stroke is not related to the presence or absence
      of symptoms, or whether the AF is paroxysmal or persistent. When an irregular
      pulse is detected it should precipitate further assessment with a 12-lead ECG. In
      patients with intermittent palpitations that may represent AF, prolonged ECG
      monitoring can be used to increase the chance of diagnosis. In patients with a
      confirmed diagnosis of AF, three areas need to be considered, stroke risk,
      symptoms, and risk of tachycardia cardiomyopathy. The CHA2DS2-VASc score is used
      to assess the stroke risk in patients with AF. Oral anticoagulation should be
      offered to those with a CHA2DS2-VASc score of 2 or more, and considered for men
      with a score of 1. The risk of severe bleeding with warfarin should also be
      assessed using the HAS-BLED score. A score of 3 or more indicates that caution is
      required when starting any anticoagulant therapy. Oral anticoagulant therapy can
      reduce the risk of stroke by around 50-70%. It should be started when the patient
      reaches 65 or if he/she develops any of the risk factors for stroke.

PMID- 25591284
TI  - Diagnosis and management of inherited cardiomyopathies.
AB  - Inherited heart conditions are the most common cause of sudden cardiac death in
      those under the age of 35 and the leading cause of non-traumatic death in young
      athletes. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart
      disease affecting 1 in 500 of the population. Some patients may exhibit severe
      left ventricular hypertrophy, others may show nothing more than an abnormal ECG.
      Left ventricular hypertrophy most commonly manifests in the second decade of
      life. Sudden death is rare and usually affects patients in the first three
      decades whereas older patients present with heart failure, atrial fibrillation
      and stroke. Arrhythmogenic right ventricular cardiomyopathy is a rare, autosomal
      dominant heart muscle disorder which affects between 1 in 1,000 and 1 in 5,000 of
      the population. Dilated cardiomyopathy (DCM) is characterised by a dilated left
      ventricle with impaired function that cannot be explained by ischaemic heart
      disease, hypertension or valvular heart disease. At least 25% of cases of DCM are
      familial. DCM may be associated with multisystem conditions such as muscular
      dystrophy. Chemotherapy and certain other drugs, alcohol abuse and myocarditis
      may also lead to a dilated and poorly contracting left ventricle. In many cases
      the first manifestation of an inherited cardiomyopathy can be a sudden cardiac
      arrest. Other presentations include chest pain or breathlessness during exertion,
      palpitations and syncope. In many of the cardiomyopathies, the diagnosis can be
      made with a standard ECG and echocardiogram. However if the diagnosis is not
      certain or the cardiologist wishes to look at the heart structure in greater
      detail, a cardiac MRI may be performed.

PMID- 25591285
TI  - Improving the management of rosacea in primary care.
AB  - Rosacea is more common in women than men and occurs more frequently in fair
      skinned individuals, usually in the middle years of life. It tends to localise to
      the cheeks, forehead, chin and nose, sometimes showing marked asymmetry. Only
      very occasionally does it involve areas other than the face. Rosacea is usually
      characterised by erythematous papules, pustules, and occasionally plaques
      (papulopustular rosacea), which fluctuate in severity, typically on a background
      of erythema and telangiectasia. In some individuals, facial redness can be
      prominent and permanent (erythematotelangiectatic rosacea). Important
      distinguishing features from acne are a lack of comedones, absence of involvement
      of extra-facial areas, and the presence of flushing. Hypertrophy of facial
      sebaceous glands, sometimes with fibrotic changes, may result in unsightly
      thickening of the skin. Men, in particular, may develop marked enlargement and
      distortion of the nose. Occasionally, the predominant feature of rosacea is
      swelling of the eyelids and firm oedematous changes elsewhere on the face.
      Involvement of the eyes is an important, underdiagnosed complication that may
      result in significant ocular morbidity. Involvement of the external eye surfaces
      by rosacea usually necessitates ophthalmological advice. There is often no
      correlation between the degree of ocular and cutaneous rosacea, and ocular
      rosacea may occur alone. Rosacea is a disfiguring condition that can have a major
      psychosocial impact, and its detrimental effect on emotional health and quality
      of life is often overlooked.

PMID- 25591286
TI  - Lower limb problems.

PMID- 25591287
TI  - Fear of syphilis and suicide. 1914.

PMID- 25591288
TI  - A lesson in understanding patients' health beliefs.

PMID- 25591289
TI  - [Dorsal intercarpal ligament capsulodesis for chronic static scapholunate
      dissociation].
AB  - OBJECTIVE: To investigate the radiographic and clinical outcomes of dorsal
      intercarpal ligament capsulodesis (DILC) procedure for chronic static
      scapholunate dissociation. METHODS: Between January 2008 and January 2011, 12
      patients with chronic static scapholunate dissociation were treated with DILC. Of
      12 cases, 10 were male and 2 were female with an average age of 42 years (range,
      20-66 years). All injuries were caused by falling. The interval from injury to
      surgery was 3-19 months (mean, 8 months). Physical examination at admission
      showed wrist tenderness and limited range of motion (ROM). Radiological
      examination showed that scapholunate gap was greater than 3 mm on posteroanterior
      view, and scapholunate angle more than 60 degrees  on the lateral view. Before
      operation, the grip strength was (25.4 +/- 8.2) kg; the wrist ROM was (56.7 +/-
      11.5) degrees  in flexion and (52.0 +/- 15.2) degrees  in extension; visual
      analogue scale (VAS) score was 6.3 +/- 1.4; and disabilities of arm, shoulder &
      hand (DASH) score was 39.5 +/- 7.4. According to Garcia-Elias staging criteria,
      all cases were rated as stage 4, indicating that the scapholunate interosseous
      ligament was completely injured and reduction could easily be obtained. Eight
      patients had wrist instability. RESULTS: Primary healing of incision was
      achieved, no complication was found. All patients were followed up 13-34 months
      (mean, 15.9 months). During surgery, all deformities were corrected completely,
      but 7 patients (58%) recurred at 1 month after Kirschner wire removal. Compared
      with preoperative ones, the scapholunate gap, scapholunate angle, radiolunate
      angle, lunocapitate angle, and wrist height ratio at 1 month after Kirschner wire
      removal and last follow-up showed no significant difference (P > 0.05); the wrist
      flexion and extension ROM were significantly decreaed to (46.8 +/- 7.2) degrees 
      and (42.0 +/- 9.0) degrees  at last follow-up (P < 0.05); the grip strength was
      significantly increased to (32.7 +/- 9.6) kg at last follow-up (P < 0.05); VAS
      score and DASH score were improved to 1.7 +/- 1.0 and 8.1 +/- 8.7 (P < 0.05).
      CONCLUSION: Carpal collapse will recur in short time after DILC. DILC is not the
      best way to treat chronic static scapholunate dissociation.

PMID- 25591290
TI  - [Operative treatment of Dubberley type 3B capitulum-trochlea fractures].
AB  - OBJECTIVE: To investigate the method and effectiveness of operative treatment of
      Dubberley type 3B capitulum-trochlea fractures. METHODS: Between January 2009 and
      December 2012, 8 cases of Dubberley type 3B capitulum- trochlea fractures were
      treated. There were 2 males and 6 females with an average age of 55 years (range,
      43-65 years). The injury was caused by falling in 6 cases, electric bicycle
      accident in 1 case, and traffic accident in 1 case. All fractures were fresh and
      closed injury. No neural or vascular injury was found. The time between injury
      and operation was 3-15 days (mean, 5.9 days). Olecranon osteotomy was performed
      by a posterior midline skin incision of the elbow; 3.0 mm Herbert compression
      screws placed from posterior to anterior, 2.4 mm L shape locking compression
      plate designed for distal radius or 2.7 mm anatomical locking compression plate
      designed for distal humerus and 1.0 mm Kirschner wires or 3.0 mm Herbert screw
      for the transverse and coronal plane in the subchondral of anterior articular
      surface were used for fixation; and the lateral and medial collateral ligaments
      were repaired. RESULTS: All incisions healed by first intention. The patients
      were followed up 12-18 months (mean, 14.5 months). The X-ray films showed that
      fracture healing was achieved at 12-24 weeks (mean, 15 weeks) in 7 cases.
      Fracture nonunion and partial bone resorption in the capitellum were observed in
      1 case. No failure of internal fixation, ulnohumeral joint instability, or
      traumatic arthritis occurred. At last follow-up, the range of motion of injured
      elbow was 0-40 degrees  in extension (mean 25.0 degrees ), 100-135 degrees  in
      flexion (mean, 116.3 degrees ), 60-70 degrees  in pronation (mean, 61.3 degrees
      ), and 80-90 degrees  in supination (mean, 81.3 degrees ). The elbow function
      score was 64-96 (mean, 81.1) according to the Broberg-Morrey evaluation criteria;
      the results were excellent in 2 cases, good in 4 cases, and fair in 2 cases with
      an excellent and good rate of 75%. The visual analogue scale (VAS) score was 0-3
      (mean, 1). CONCLUSION: For Dubbelley type 3B capitulum-trochlea fractures, an
      early anatomic reconstruction of capitellar and trochlea, repair of the medial
      and lateral collateral ligament, and early active mobilization can obtain good
      functional

PMID- 25591291
TI  - [Effectiveness comparison of proximal femoral nail anti-rotation and locking
      compression plate for intertrochanteric fractures with lateral unsubstantial
      femoral wall in elderly patients].
AB  - OBJECTIVE: To compare the effectiveness of the proximal femoral nail anti
      rotation (PFNA) and locking compression plate (LCP) in the treatment of
      intertrochanteric fractures with the lateral unsubstantial femoral wall in
      elderly patients. METHODS: Between May 2009 and August 2012, 69 elderly patients
      with intertrochanteric fractures with the lateral unsubstantial femoral wall were
      treated. Fractures were fixed with PFNA in 36 patients (PFNA group), and with LCP
      in 33 patients (LCP group). There was no significant difference in gender, age,
      injury cause, side of fracture, and fracture AO type between 2 groups (P > 0.05).
      The incision length, operation time, intraoperative blood loss, total blood loss,
      fluoroscopy frequency, time for ambulation, and early (within 3 months) and late
      (more than 12 months) complications were compared. Fracture healing was assessed
      according to X-ray reexamination, the function of the hip joint was assessed
      according to the Harris hip scoring system. RESULTS: The incision length,
      operation time, intraoperative blood loss, and time for ambulation of PFNA group
      were significantly less than those of LCP group (P < 0.05), but the fluoroscopy
      frequency of PFNA group was significantly more than that of LCP group (P < 0.05).
      There was no significant difference in total blood loss between 2 groups (t = 
      1.686, P = 0.096). The patients were followed up 12-24 months in PFNA group and
      15-30 months in LCP group. The X-ray reexamination revealed fracture healing at
      (12.667 +/- 2.527) weeks in patients of PFNA group, and at (13.364 +/- 1.194)
      weeks in the others of LCP group except 1 case of nonunion, showing no
      significant difference (t = -1.443, P = 0.154). There was no significant
      difference in Harris hip score between PFNA group (84.611 +/- 7.076) and LCP
      group (81.785 +/- 7.500) at 12 months after operation (t = 1.626, P = 0.109). The
      early complication rate and late complication rate were 16.7% (6/36) and 5.6%
      (2/36) in PFNA group and were 9.1% (3/33) and 9.1% (3/33) in LCP group, all
      showing no significant difference between 2 groups (chi2 = 0.871, P = 0.481; chi2
      = 0.320, P = 0.665). CONCLUSION: Both PFNA and LCP have good effectiveness in
      the,treatment of intertrochanteric fractures with the lateral unsubstantial
      femoral wall in the elderly patients. Each has its own advantages and
      disadvantages.

PMID- 25591292
TI  - [Electromagnetic navigation interlocking intramedullary nail technology for
      treatment of femoral shaft fractures].
AB  - OBJECTIVE: To explore the value of electromagnetic navigation interlocking
      intramedullary nail in the treatment of femoral shaft fracture. METHODS: Between
      July 2012 and October 2013, 53 cases of femoral shaft fracture were treated.
      There were 40 males and 13 females, aged 16-52 years (mean, 38.3 years). The
      causes of injury were traffic accident in 28 cases, falling from height in 11
      cases, falling in 7 cases, crush injury in 4 cases, and other in 3 cases. Of 53
      cases, there were 3 cases of open fracture (Gustilo I degree) and 50 cases of
      closed fracture. Fracture was located in the proximal femur in 17 cases, middle
      femur in 29 cases, and distal femur in 7 cases. According to Winquist
      classification, 7 cases were rated as type I, 8 cases as type II, 22 cases as
      type III, and 16 cases as type IV; according to AO classification, 18 cases were
      rated as type 32-A, 28 cases as type 32-B, and 7 cases as type 32-C. The time
      from injury to operation was 3-11 days (mean, 5 days). Distal interlocking
      intramedullary nail was implanted using electromagnetic navigation. RESULTS: The
      distal locking nail operation with interlocking intramedullary nail was
      successfully completed under electromagnetic navigation; the one-time success
      rate of distal locking nail operation reached 100%; and the locking nail time was
      5.0-9.5 minutes (mean, 7.0 minutes). Healing of incision by first intention was
      obtained after operation, and no complication of skin necrosis, infection, and
      sinus tract occurred. Fifty-three cases were all followed up 5-12 months (mean, 9
      months). One case had hip pain and weaken middle gluteal muscle strength, and the
      symptoms disappeared after removing the nail. During the follow-up period, no
      broken nails, nail exit, infection, or re-fracture occurred. All fractures
      achieved clinical healing, and the healing time was 8-22 weeks (mean, 14.5
      weeks). In 49 patients followed up 8 months, the Lysholm score was excellent in
      44 cases, good in 4 cases, and acceptable in 1 case, with an excellent and good
      rate of 98%. CONCLUSION: Electromagnetic navigation system is safe and reliable,
      with the advantages of high positioning accuracy, short operation time, and no
      radiation, the clinical application of the system for distal locking nail
      operation can obtain excellent short-term effectiveness.

PMID- 25591293
TI  - [Short-term effectiveness of unicompartmental knee arthroplasty for medial
      compartmental knee osteoarthritis].
AB  - OBJECTIVE: To evaluate the short-term effectiveness of unicompartmental knee
      arthroplasty (UKA) for medial compartmental osteoarthritis of the knee. METHODS:
      Between January 2008 and October 2013, 18 patients with medial compartmental
      osteoarthritis of the knee were treated by UKA, including 11 males and 7 females
      with an average age of 67.2 years (range, 60-72 years). The disease duration
      ranged from 3 to 5 years (mean, 3.7 years). All patients had loading pain and
      walk-associated pain of the medial compartmental knee. The preoperative visual
      analogue scale (VAS) score was 6.8 +/- 1.4. The full-length radiograph of lower
      limb and anteroposterior and lateral radiographs of the knee showed medial
      compartmental osteoarthritis of the knee. According to Ahlback staging, 8 knees
      were at stage II and 10 knees at stage III. The knee range of motion (ROM) was
      (112.3 +/- 11.3) degrees , and the angle of genu varus was (13.2 +/- 1.3) degrees
      . The American Hospital for Special Surgery (HSS) score was 59.0 +/- 6.4.
      RESULTS: Primary healing of incision was obtained in all patients, and no
      infection or lower limb deep venous thrombosis occurred. All of the patients were
      followed up 6-50 months (mean, 28 months). No prosthetic loosening and
      dislocation or lesions of contralateral compartment and patellofemoral joint
      developed. At 6 months after operation, the VAS score was significantly reduced
      to 2.8 +/- 1.2 (t = 9.20, P = 0.00); most of patients achieved significant relief
      of pain. The HSS score was significantly increased to 92.0 +/- 3.1 (t = 19.69, P
      = 0.00); and the results were excellent in 12 cases, good in 5 cases, and poor in
      1 case, with an excellent and good rate of 94.4%. The knee ROM was (115.2 +/-
      10.2) degrees , showing no significant difference when compared with preoperative
      one (t = -0.81, P = 0.23). The alignment of limbs showed that the angle of genu
      varus was significantly reduced to 6.8 +/- 2.1) degrees  (t = 10.99, P = 0.00).
      CONCLUSION: UKA has satisfactory short-term effectiveness in the treatment of
      medial compartmental knee osteoarthritis, however, long-term effectiveness need
      further studies.

PMID- 25591294
TI  - [Staged treatment of infectious long bone defect in lower extremity].
AB  - OBJECTIVE: To explore the clinical application and effectiveness of antibiotic
      loaded cement spacer combined with free fibular graft in the staged treatment of
      infectious long bone defect in the lower extremity. METHODS: A retrospective
      analysis was made on the clinical data from 12 patients with infectious long bone
      defect in the lower extremity between June 2010 and June 2012. Of the 12 cases,
      there were 9 males and 3 females with an average age of 33 years (range, 19-46
      years), including 3 cases of femoral shaft bone defect, 7 cases of tibial shaft
      bone defect, and 2 cases of metatarsal bone defect. The causes were traffic
      accident injury in 7 cases, crashing injury in 3 cases, and machine extrusion
      injury in 2 cases. The length of bone defect ranged from 6 to 14 cm (mean, 8 cm).
      The soft tissue defect area ranged from 5.0 cm x 3.0 cm to 8.0 cm x 4.0 cm
      companied with tibial shaft and metatarsal bone defect in 9 cases. The sinus
      formed in 3 femoral shaft bone defects. The time between injury and operation was
      1-4 months (mean, 2 months). At first stage, antibiotic-loaded cement spacer was
      placed in the bone defect after debridement and the flaps were used to repair
      soft tissue defect in 9 cases; at second stage (6 weeks after the first stage),
      defect was repaired with free fibular graft (7-22 cm in length, 14 cm on average)
      after antibiotic-loaded cement spacer removal. The area of the cutaneous fibular
      flap ranged from 6.0 cm x 4.0 cm to 10.0 cm x 5.0 cm in 10 cases. RESULTS: All
      wounds healed by first intention, and the healing time was 12-18 days, 14 days on
      average. Twelve cases were followed up 12-36 months (mean, 17 months). Bone
      healing time ranged from 4 to 6 months (5.5 months on average). The cutaneous
      fibular flap had good appearance. The function at donor site was satisfactory; no
      dysfunction of the ankle joint or tibial stress fracture occurred after
      operation. The mean Enneking score was 25 (range, 20-28) at last follow-up.
      CONCLUSION: Infection can be well controlled with the antibiotic-loaded cement
      spacer during first stage operation, and free fibular graft can increase the bone
      defect healing rate at second stage. Staged treatment is an optimal choice to
      treat infectious long bone defect in the lower extremity.

PMID- 25591295
TI  - [Biomechanical study on repairing distal tibiofibular syndesmosis injuries with
      artificial ligaments].
AB  - OBJECTIVE: To investigate the biomechanical properties of artificial ligament in
      the treatment of injuries to distal tibiofibular syndesmosis so as to provide a
      scientific basis for clinical application. METHODS: Sixteen fresh ankle specimens
      were harvested from 8 normal fresh-frozen cadavers. The initial tests were
      performed on 16 intact specimens (group A) and then the distal tibiofibular
      syndesmosis injury models were made (group B); the distal tibiofibular
      syndesmosis was fixed with artificial ligament in 8 specimens (group C) and with
      cannulated lag screw in the other 8 specimens (group D). The pros and cons of
      different fixation methods were analyzed by displacement, stress shielding
      effect, the strength and stiffness of ankle joints, the contact area of
      tibiotalar articular surface and the contact stress. RESULTS: Under the
      physiological loading or combined with external rotation moment, the displacement
      of group C was significantly lower than that of groups B and D (P < 0.05), but no
      significant difference was found between groups A and C (P > 0.05); and there
      were significant differences among groups A, B, and D (P < 0.05). The rates of
      stress shielding in the tibia and fibula of group C were significantly lower than
      those of group D (t = -71.288, P = 0.000; t = -97.283, P = 0.000). The stress
      strength in tibia of group C was significantly higher than that of groups A and D
      (P < 0.05), but no significant difference was found between groups A and D (P >
      0.05). Group C had the highest stress strength in fibula, followed by group A,
      group D had the lowest; differences were significant among 3 groups (P < 0.05).
      There was no significant difference in shear strength among groups A, C, and D (P
      > 0.05). The axial stiffness in tibia of group D was significantly lower than
      that of groups A and C (P < 0.05), but no significant difference was found
      between groups A and C (P > 0.05). The axial stiffness in fibula of group C was
      significantly higher than that of groups A and D (P < 0.05), but no significant
      difference was found between groups A and D (P > 0.05). Group C had the highest
      shear stiffness in tibia and fibula, followed by group D,group A had the lowest;
      differences were significant among 3 groups (P < 0.05). In groups A, C, and D,
      the contact area of tibiotalar articular surface gradually reduced, and the
      contact stress gradually increased, and differences were significant among 3
      groups (P < 0.05). CONCLUSION: Fixation of distal tibiofibular syndesmosis injury
      with artificial ligament can better meet the physiological functions of the
      distal tibiofibular syndesmosis and has lower stress shielding, better stress
      distribution. Hopefully, it can reduce the complications of the distal
      tibiofibular syndesmosis injuries and become a better treatment choice.

PMID- 25591296
TI  - [Manufacture and clinical application of medical metal debris adsorption
      apparatus].
AB  - OBJECTIVE: To introduce a medical metal debris adsorption apparatus and to
      discuss the application value in removal of locking plate internal fixation.
      METHODS: Between January 2011 and May 2013, 83 cases underwent removal of locking
      plate fixation. There were 44 males and 39 females, aged 21-59 years (mean, 35.4
      years). The time from the first operation to internal fixation removal was 16-40
      months (mean, 22.6 months). Thirty-two screws of 9 patients were removed
      difficultly due to slide fastener. The screws were removed eventually after
      plates and screws were separated by grinding locking screw with manganese steel
      drill. In the process of grinding, the medical metal debris adsorption apparatus
      was used in 16 screws of 4 patients (group A), and was not used in 16 screws of 5
      patients (group B). The operation time, removal time of single slipping screw,
      intraoperative blood loss, and the score of metal debris residues were compared
      between 2 groups. And the postoperative complications were recorded. RESULTS: A
      total of 658 screws were removed, and 32 slipping screws were found, accounting
      for 4.86%. The lock screw slipping rates of 3.5 mm and 4.5 or 5.0 mm respectively
      were 6.53% and 2.31%; and the lock screw slip ping rates of internal fixation
      time < 2 years and > 2 years respectively were 3.21% and 6.08%. The operation
      time, removal time of single slipping screw, intraoperative blood loss, and the
      score of metal debris residues of group A were significantly lower than those of
      group B (P < 0.05). Re-fracture (1 case) and incision infection (1 case) occurred
      in group B, and no complication was observed in group A. The cases of 2 groups
      were followed up 8-35 months (mean, 23.4 months). No heterotopic ossification
      occurred in both groups during the follow-up. CONCLUSION: The medical metal
      debris adsorption apparatus can significantly shorten the operation time, reduce
      the residual metal debris and surgical bleeding when removing the slipping screws
      in removal of locking plate internal fixation.

PMID- 25591297
TI  - [Establishment of microinvasive modle of chronic rotator cuff injury in rats].
AB  - OBJECTIVE: To establish a model of chronic rotator cuff injury by inducing
      subacromial impingement syndrome in rats, so as to lay a foundation for further
      study on the mechanism and treatment of chronic rotator cuff injury. METHODS: The
      polyether-ether-ketone implants were designed and made with three-dimensional
      printing technique. In 48 male Sprague Dawley rats [weighing, (277.25 +/- 22.03)
      g], one shoulder joint was selected randomly as the experimental group; in the
      experimental group, the implant was pierced into shoulder joint close to the
      acromion medial side and was pierced out under acromion close to the deltoid
      trailing edge; the penetrating part of implant was cut off after the implanting
      part was fixed with 4# braided silk suture. No any treatment was performed on the
      contralateral shoulder of 24 rats as control group; and the implants were
      immediately removed after they were pierced into the contralateral shoulder joint
      of the other 24 rats as sham- operation group. All the rats were exposed to 30
      minutes of downhill running at 17 m/minute (-13.5 degrees ) every day at 4 days
      after operation and the general condition of rats was observed. At 2, 4, 6, and 8
      weeks after operation, 12 rats were sacrificed to collect shoulder joint samples.
      The hard tissue slices was used for Van Gieson staining and histological
      observation of the supraspinatus tendon. RESULTS: All rats survived to the end of
      experiment, without infection. The rats suffered limp at 2-3 days after
      operation, and the gait of most rats returned to normal at 4 days after
      operation. The histological results showed that the supraspinatus tendon had
      smooth edge, without split layers or breakage in the control group and sham
      operation group. In the experimental group, the implants were positioned
      accurately without dislocation; 4 kinds of typical pathological changes were
      observed. Partial-thickness tear on bursal side appeared at 2 weeks (5 rats) and
      4 weeks (2 rats), showing no significant difference between at 2 and 4 weeks (P >
      0.05); intratendinous gap formed mainly at 4 weeks (10 rats) and 6 weeks (11
      rats), showing significant differences when compared with that at 2 weeks (2
      rats) (P < 0.05) and 8 weeks (2 rats) (P < 0.05); partial-thickness tear on
      articular side mainly appeared at 6 weeks (8 rats), showing significant
      difference when compared with that at other time points (P < 0.05); full
      thickness tear was found mainly at 8 weeks (10 rats), showing significant
      differences when compared with that at other time points (P < 0.05). CONCLUSION:
      A model of chronic rotator cuff injury is successfully established in rats
      through microinvasive implantation of subacromial impingement syndrome inducing
      implants and the pathological changes in this model are highly similar to the
      clinical pathological progress.

PMID- 25591298
TI  - [Early outcome of different operation methods in treatment of multi-segmental
      cervical spondylotic myelopathy].
AB  - OBJECTIVE: To explore the early outcome of 3 different operation methods in the
      treatment of multi- segmental cervical spondylotic myelopathy (CSM). METHODS: A
      retrospective analysis was made on the clinical data of 74 patients with multi
      segmental CSM treated between January 2011 and March 2013. The patients were
      divided into 3 groups according to operation methods: open-door expansive
      laminoplasty by plate was used in 21 patients (group A), open-door expansive
      laminoplasty by anchor fixation in 28 patients (group B), and conventional
      unilaterally open-door expansive laminoplasty in 25 patients (group C). There was
      no significant difference in gender, age, disease druation, affected segments,
      preoperative Japanese Orthopaedic Association (JOA) score, and cervical curvature
      of C2-7 among 3 groups (P > 0.05). The peration time, intraoperative blood loss,
      and JOA score, cervical curvature, incidence of axial symptoms were recorded.
      RESULTS: There was no significant difference of operation time and intraoperative
      blood loss between group A and group B (P > 0.05). All incisions healed by first
      intention. Cerebrospinal leak occurred in 2 cases (1 case of group B and 1 case
      of group C) and C5 nerve root palsy in 4 cases (2 cases of group A, 1 case of
      group B, and 1 case of group C); all the symptoms disappeared after symptomatic
      treatment. The patients were followed up 12-39 months (mean, 18.3 months). The
      position of internal fixation was good without loosening and pulling out in
      groups A and B. Reclosed open-door was observed in 2 cases of group C, which
      disappeared after the second surgery. The JOA scores were significantly increased
      at 6 months after operation when compared with preoperative scores in groups A,
      B, and C (P < 0.05). The cervical curvature of C2-7 at postoperation was
      significantly improved when compared with preoperative one in groups B and C (P <
      0.05) except group A (P > 0.05) . There weresignificant differences in JOA score
      and the cervical curvature among 3 groups at 6 months after operation (P < 0.05).
      The incidence of axial symptoms were 4.76% (1/21), 35.71% (10/28), and 72.00%
      (18/25) in groups A, B, and C respectively, showing significant differences (P <
      0.017). CONCLUSION: Open-door expansive laminoplasty by plate has better early
      outcome than open-door expansive laminoplasty by anchor fixation and conventional
      unilaterally open-door expansive laminoplasty in the treatment of multi-segmental
      CSM.

PMID- 25591299
TI  - [Treatment of thoracolumbar burst fractures by posterior laminotomy decompression
      and bone grafting via injured vertebrae].
AB  - OBJECTIVE: To study the effectiveness of posterior laminotomy decompression and
      bone grafting via the injured vertebrae for treatment of thoracolumbar burst
      fractures. METHODS: Between November 2010 and November 2012, 58 patients with
      thoracolumbar burst fractures were treated by posterior fixation combined with
      posterior laminotomy decompression and intervertebral bone graft in the injured
      vertebrae. There were 40 males and 18 females with a mean age of 48 years (range,
      25-58 years). According to Denis classification, 58 cases had burst fractures
      (Denis type B); based on neurological classification of spinal cord injury by
      American Spinal Injury Association (ASIA) classifications, 5 cases were rated as
      grade A, 18 cases as grade B, 20 cases as grade C, 14 cases as grade D, and 1
      case as grade E. Based on thoracolumbar burst fractures CT classifications there
      were 5 cases of type A, 20 cases of type B1, 10 cases of type B2, and 23 cases of
      type C. The time between injury and operation was 10 hours to 9 days (mean, 7.2
      days). The CT was taken to measure the space occupying of vertebral canal. The X
      ray film was taken to measure the relative height of fractured vertebrae for
      evaluating the vertebral height restoration, Cobb angle for evaluating the
      correction of kyphosis, and ASIA classification was conducted to evaluate the
      function recovery of the spinal cord. RESULTS: The operations were performed
      successfully, and incisions healed primarily. All the patients were followed up
      12-18 months (mean, 15 months). CT showed good bone graft healing except partial
      absorption of vertebral body grafted bone; no loosening or breakage of screws and
      rods occurred. The stenosis rates of fractured vertebral canale were 47.56% +/-
      14.61% at preoperation and 1.26% +/- 0.62% at 1 year after operation, showing
      significant difference (t = 24.46, P = 0.00). The Cobb angles were (16.98 +/-
      3.67) degrees  at preoperation, (3.42 +/- 1.45) degrees  at 1 week after
      operation, (3.82 +/- 1.60) degrees  at 1 year after operation, and (4.84 +/-
      1.70) degrees  at 3 months after removal of internal fixation, showing
      significant differences between at pre- and post-operation (P < 0.05). The
      relative heights of fractured vertebrae were 57.10% +/- 6.52% at preoperation,
      96.26% +/- 1.94% at 1 week after operation, 96.11% +/- 1.97% at 1 year after
      operation, and 96.03% +/- 1.96% at 3 months after removal of internal fixation,
      showing significant differences between at pre- and post-operation (P < 0.05). At
      1 year after operation, the neural function was improved 1-3 grades in 56 cases.
      Based on ASIA classifications, 1 case was rated as grade A, 4 cases as grade B,
      10 cases as grade C, 23 cases as grade D, and 20 cases as grade E. CONCLUSION:
      Treatment of thoracic and lumbar vertebrae burst fractures by posterior
      laminotomy decompression and bone grafting via the injured vertebrae has
      satisfactory effectiveness, which can reconstruct vertebral body shape and height
      with spinal cord decompression and good vertebral healing. It is a kind of
      effective solution for thoracolumbar burst fracture.

PMID- 25591300
TI  - [Comparison of effectiveness between two surgical methods in treatment of
      thoracolumbar brucella spondylitis].
AB  - OBJECTIVE: To compare the effectiveness between the method of simple posterior
      debridement combined with bone grafting and fusion and internal fixation and the
      method of one-stage anterior radical debridement combined with bone grafting and
      fusion and posterior internal fixation in the treatment of thoracolumbar brucella
      spondylitis so as to provide the reference for the clinical treatment. METHODS: A
      retrospective analysis was made on the clinical data of 148 cases of
      thoracolumbar brucella spondylitis between January 2002 and January 2012. Simple
      posterior debridement combined with bone grafting and fusion and internal
      fixation was used in 78 cases (group A), and one-stage anterior radical
      debridement combined with bone grafting and fusion and posterior internal
      fixation in 70 cases (group B). There was no significant difference in gender,
      age, disease duration, involved vertebral segments, erythrocyte sedimentation
      rate (ESR), visual analogue scale (VAS) score, neural function grade of America
      Spinal Injury Association (ASIA), and kyphosis Cobb angle before operation
      between 2 groups (P > 0.05). The peri operation period indexes (hospitalization
      time, operation time, and intraoperative blood loss) and the clinical
      effectiveness indexes (VAS score, ASIA grade, Cobb angle, and ESR) were compared;
      the bone fusion and the internal fixation were observed. RESULTS: Incision
      infection and paravertebral and/or psoas abscess occurred in 2 and 3 cases of
      group A respectively. All incisions healed by first intention and 2 cases had
      pneumothorax in group B. The operation time and the hospitalization time of group
      A were significantly shorter than those of group B (P < 0.05), and the
      intraoperative blood loss of group A was significantly lower than that of group B
      (P < 0.05). All of the cases in 2 groups were followed up 14- 38 months, 25
      months on average. The VAS, ESR, and Cobb angle were significantly decreased at
      each time point after operation when compared with preoperative ones in 2 groups
      (P < 0.05), but no significant difference was found between 2 groups (P > 0.05).
      The neurological function was significantly improved at 3 months after operation;
      there were 1 case of ASIA grade C, 14 cases of grade D, and 63 cases of grade E
      in group A, and there were 1 case of grade C, 11 cases of grade D, and 58 cases
      of grade E in group B; and difference was not significant (Z = 0.168, P = 0.682).
      The grafting bone fusion was observed in both groups. The fusion time was (8.7 +/
      0.3) months in group A and (8.6 +/- 0.4) months in group B, showing no
      significant difference (t = 0.591, P = 0.601) was found. At last follow-up, no
      loosening or fracture of internal fixation was found. CONCLUSION: Based on
      regular medicine therapy, the effectiveness of the two methods is satisfactory in
      the treatment of thoracolumbar brucella spondylitis as long as the operation
      indications should be controlled strictly.

PMID- 25591301
TI  - [Clinical anatomy study on autonomic nerves related to anterior approach lumbar
      surgery ].
AB  - OBJECTIVE: To understand the location characteristics of the lumbosacral
      autonomic nerve plexus and the morphological changes so as to provide the
      anatomic theoretical basis for the protection of autonomic nerve during the lower
      lumbar anterior approach operation. METHODS: A random anatomic investigation was
      carried out on 19 formalin-treated adult cadavers (15 males and 4 females; aged
      44-78 years, mean 64 years). The anterior median line (connection of suprasternal
      fossa point and the midpoint of the symphysis pubis) was determined, and the
      characteristics of abdominal aortic plexus (AAP), inferior mesenteric plexus
      (IMP), and superior hypogastric plexus (SHP) were observed. The relationship
      between the autonomic nerve and the anterior median line was measured and
      recorded. RESULTS: APP and IMP were found to be located chiefly in front of the
      abdominal aorta in a reticular pattern, and the nerve fibers of the two nerve
      plexuses were more densely at the left side of abdominal aorta than at the right
      side. Superior hypogastric plexus showed more distinct main vessel variations,
      including 4 types. The main vessel length of the SHP was (59.38 +/- 12.86) mm,
      and the width was (11.25 +/- 2.92) mm. The main vessels of SHP were mainly
      located at the left side of the ventral median line (10, 52.6%) and anterior
      lumbar vertebra (13, 68.4%). The main vessels extended down to form the left and
      right hypogastric nerves. CONCLUSION: It is applicable to expose the nerve from
      the right side of centrum and move the autonomic nerve and blood vessel as a
      whole during anterior lower lumbar operation. In this way, the dissection to
      separate nerve plexus is not needed, thus nerve injury can be avoided to the
      largest extent.

PMID- 25591302
TI  - [Application of temporary balloon blocking technique in bone tumors surgery under
      the aid of CT angiography].
AB  - OBJECTIVE: To study the value of CT angiography (CTA) in the surgical treatment
      of bone tumors with the temporary balloon blocking technique. METHODS: A
      retrospective analysis was made on the clinical data of 36 bone tumor patients
      between April 2008 and October 2013. There were 22 males and 14 females, aged
      from 25 to 83 years (mean, 46 years). The tumor located at the sacrococcygeal
      region in 17 cases, at the ilium in 12 cases, at the pubis in 5 cases, and at the
      proximal femur in 2 cases. Before surgery, CTA was performed to measure the
      external diameter of aortaventralis and arteria iliac communis, and the distance
      between the low renal artery and the abdominal aortic bifurcation as well as mark
      the anatomical relationship between the low renal artery, the abdominal aortic
      bifurcation and bony landmarks of vertebral body. According to these data,
      suitable balloon was chosen and the balloon positioning was guided in the surgery
      to completely excise tumor assisted by balloon blocking technique. RESULTS: The
      CTA results showed that the external diameter of aortaventralis and arteria
      iliaca communis was (1.545 +/- 0.248) cm and (1.060 +/- 0.205) cm respectively,
      and the distance between the low renal artery and the abdominal aortic
      bifurcation was (10.818 +/- 1.165) cm. The three-dimensional reconstruction
      showed that the opening of the low renal artery was mainly located at L1 (16/36,
      44.4%) and the abdominal aortic bifurcation mainly located at L4 (22/36, 61.1%).
      Effective block of abdomial aorta was performed; the blood pressure obviously
      increased in 3 cases after balloon inflation, and pulse of the left dorsal artery
      of the foot decreased in 1 case after removal of balloon, which were relieved
      after expectant treatment. The operation time was 118-311 minutes; the
      intraoperative blood loss was 200-1800 mL, 21 patients were given blood
      transfusion, and the amount of blood transfusion was 400-1200 mL; and the aortic
      clamping time was 40-136 minutes. All patients were followed up 5-44 months
      (mean, 21 months). According to Enneking standard, the results were excellent in
      9 cases, good in 20 cases, fair in 5 cases, and poor in 2 cases at 3 months after
      operation. There were 10 cases of dysfunction of urination and defecation, 2
      cases of tumor recurrence, and 3 cases of death after surgery. CONCLUSION: CTA
      and three-dimensional reconstructions technique can accurately measure the
      external diameter of aortaventralis and arteria iliaca communis and the distance
      between low renal artery and abdominal aortic bifurcation and offer great help to
      choose appropriate balloon and locate the balloon during surgery. The balloon
      blocking technique under the assistance of CTA can obviously reduce
      intraoperative blood loss and tumor recurrence, supply a clear view in surgery
      and shorten the operation time.

PMID- 25591303
TI  - [Clinical application of link-pattern lateral popliteal artery perforator flap in
      repair of popliteal fossa scar].
AB  - OBJECTIVE: To discuss the feasibility and effectiveness of link-pattern lateral
      popliteal artery perforator flap in repairing popliteal fossa scar contracture in
      children or teenagers. METHODS: Between January 2009 and January 2013, 12
      patients with popliteal fossa scar were admitted. Of them, 7 cases were male and
      5 cases were female, aged from 3 to 17 years (median, 12 years). The disease
      duration was from 6 months to 5 years (median, 3 years). Wound was repaired with
      link-pattern lateral popliteal artery perforator flap after remission of
      popliteal fossa scar. The wound ranged from 6 cm x 4 cm to 10 cm x 7 cm, and the
      flap size ranged from 7 cm x 4 cm to 12 cm x 9 cm. The flap was with lateral
      sural cutaneous nerve in 5 cases, and lateral sural cutaneous nerve was retained
      at the donor area of 7 cases. The donor site was repaired using split- thickness
      skin graft. RESULTS: All pedicled flaps and skin graft survived smoothly after
      operation. The wound at donor site healed by first intention. All the cases were
      followed up 12-36 months, with an average of 18 months. The flaps had good color,
      texture, and shape; scar obviously became softened, without hyperplasia or
      ulceration. The patients were free from lameness with knee range of motion of 0
      180 degrees . The squatting function was normal. Grafting skin was smooth in the
      donor area of the calf, without depression or scar hyperplasia. The senses of
      posterior-inferior calf and lateral of foot decreased or disappeared in 5 cases
      of flaps with lateral sural cutaneous nerve; at 6 months after operation, two
      point discrimination was 12-14 mm (mean, 13 mm). The posterior-inferior calf was
      numb and discomfort in 7 cases of flaps with retained lateral sural cutaneous
      nerve; but after 3-6 months, the sense was obviously recovered, with no sense
      loss; at 6 months after operation, two-point discrimination was 5-7 mm (mean, 6
      min). CONCLUSION: Link-pattern lateral popliteal artery perforator flap has
      reliable blood supply and the operation was simple. The cutaneous nerve can be
      retained in donor area. It is an ideal method for repairing wound after remission
      of popliteal fossa scar in children or teenagers.

PMID- 25591304
TI  - [Treatment of leg, foot, and ankle wounds with saphenous neurocutaneous vascular
      flaps combined with assembly external frisket for fixation in parallel-leg
      position].
AB  - OBJECTIVE: To explore the effectiveness of a new method to repair severe soft
      tissue defects of the leg, foot, and ankle with contralateral saphenous
      neurocutaneous vascular flaps combined with assembly external frisket for
      fixation in parallel-leg position. METHODS: Between August 2009 and August 2013,
      29 cases with leg, foot, or ankle wound were treated. There were 18 males and 11
      females, with an average age of 37.6 years (range, 11-65 years). The interval of
      injury and operation was 14-36 days (mean, 22.3 days). The locations were the
      planta pedis and heel in 5 cases, the dorsal foot in 2 cases, the ankle in 4
      cases, middle and lower leg in 14 cases, and upper leg in 4 cases. The area of
      trauma ranged from 5 cm x 3 cm to 19 cm x 9 cm. The assembly external frisket was
      used for fixation in parallel-leg position; a bridge flap was transplanted to
      repair defects, and the area of flap ranged from 6 cm x 4 cm to 22 cm x 11 cm.
      The donor sites were directly sutured or repaired with skin graft. The pedicle of
      the bridge flap was cut off and the assembly external frisket was removed after 3
      4 weeks. RESULTS: The flaps in all patients survived completely; primary healing
      of wound and incision at donor site was obtained. The patients were followed up 6
      18 months (mean, 13.2 months). The appearance of flaps was satisfactory, and the
      sensation of the heel recovered. Moreover, the patients had a comfortable
      feeling, and the ankle and knee joints can move freely, and had good function.
      CONCLUSION: The assembly external frisket in parallel-leg position instead of
      cross-leg can make patients comfortable position, and achieve reliable fixation.
      The saphenous neurocutaneous vascular flap has the advantages of no need for
      anastomosis vein and for sacrifice of the main vein. Contralateral saphenous
      neurocutaneous vascular flap combined with assembly external frisket for fixation
      in parallel-leg position is a favorite method to repair severe soft tissue
      defects of the leg, foot, and ankle.

PMID- 25591305
TI  - [Evaluation of multi-slice spiral ct scan and image reconstruction technology in
      estimating costal cartilage volume].
AB  - OBJECTIVE: To investigate the accuracy of multi-slice spiral CT (MSCT) scan and
      image reconstruction technology for measuring morphological parameters of costal
      cartilages and to evaluate the volume of costal cartilages. METHODS: Between
      March and August 2013, 75 patients with congenital microtia and scheduled for
      auricle reconstruction were included in the study. Of 75 patients, there were 49
      males and 26 females with a mean age of 8 years and 5 months (range, 5 years and
      7 months to 32 years and 7 months) and a mean weight of 29.5 kg (range, 21-82
      kg). A Philips Brilliance 64 MSCT machine was used to scan 1st-12th costal
      cartilages with the parameters based on the age and weight of the patients. All
      the data were transported to the workstation for reconstructing the image of the
      costal cartilages with the technique of maximum intensity projection (MIP) and
      volume rendering technique (VRT). Then the morphologies of costal cartilages were
      observed through the images on VRT; the width of the costal cartilaginous ends
      close to ribs (W) and the length of thetotal cartilage (L) were measured and
      compared with their counterparts (W' and L') after the costal cartilages were
      harvested during the processes of auricle reconstructions to analyze consistency
      between these two sets of data. RESULTS: The morphologies of ribs and costal
      cartilages shown on VRT image got fine sharpness, verisimilitude, and
      stereoscopic impressions. A total of 192 costal cartilages were examined. The
      results showed that the widths of the costal cartilaginous ends close to ribs (W)
      was (9.69 +/- 1.67) mm, and W' was (9.73 +/- 1.64) mm, showing no significant
      difference between W and W' (t = -1.800, P = 0.073), and interclass correlation
      coefficient (ICC) test showed Cronbach's alpha = 0.993. The length of the total
      cartilage (L) was (83.03 +/- 23.86) mm, and L' was (81.83 +/- 16.43) mm, showing
      no significant difference between L and L' (t = -1.367, P = 0.173), and ICC test
      showed Cronbach's alpha = 0.904. Linear-regression analysis showed L = 1.28 x L' 
      21.93 (R2 = 0.780, F = 673.427, P = 0.000). The results suggested there was a
      good consistency between these two sets of data. CONCLUSION: Scanning costal
      cartilages with appropriate parameters and reconstructing the cartilaginous image
      with MIP is an effective method to measure the width and length of costal
      cartilage and to estimate costal cartilage volume, which can provide accurate
      reference for plastic surgery together with reading the morphology from the image
      on VRT.

PMID- 25591306
TI  - [Application of biological mesh for reconstruction of pelvic floor in patients
      with perineal hernia].
AB  - OBJECTIVE: To investigate the effectiveness of repair procedure using biological
      mesh with Onlay-Reinforce technique in patients with perineal hernia. METHODS:
      Between January 2005 and December 2012, 9 patients with perineal hernia after
      laparoscopic abdominoperineal resection for rectal cancer (Miles operation) were
      treated. There were 3 males and 6 females with a mean age of 70 years (range, 61
      78 years). The disease duration was 1-9 months (mean, 4.5 months). The most
      beginning symptom was distending pain in perineal region, and then reducible mass
      was found without bowel incarceration. All patients underwent hernia repair using
      biological mesh with Onlay-Reinforce technique through original perineal
      incision. RESULTS: The hernial size was 9.8-20.5 cm2 (mean, 16.0 cm2); the size
      of biological mesh was 58-80 cm2 (mean, 70.2 cm2); and the intraoperative blood
      loss was 10-80 mL (mean, 50.5 mL). All of the patients underwent repair operation
      successfully. The operation time was 45-90 minutes (mean, 60.6 minutes); and the
      hospitalization time was 4-7 days (mean, 5.9 days). One patient had urine
      retention, which was relieved after 7 days indwelling catheter. All the wounds
      healed by first intention without infection. The patients were followed up 14.5
      60.7 months (mean, 37.8 months). No chronic pain, obvious foreign body sensation,
      or hernia recurrence developed. CONCLUSION: Use of biological mesh with Onlay
      Reinforce technique for the repair ofperineal hernia after Miles operation is
      safe and effective.

PMID- 25591307
TI  - [Diagnosis and treatment of acute peroneal artery ischemia syndrome].
AB  - OBJECTIVE: To put forward the concept of acute peroneal artery ischemia syndrome,
      and to study its typical clinical manifestations and imaging features so as to
      provide the basis of the evidence-based medicine for the diagnosis and treatment
      of acute peroneal artery ischemia. METHODS: Between October 2009 and December
      2012, 3 cases (2 males and 1 female, aged 57, 68, and 71 years) of acute peroneal
      artery ischemia syndrome were treated. All the patients displayed typical three
      symptoms of "peroneal artery blood supply zone pale/red + severe pain of the
      gastrocnemius muscle + acute drop foot". Medical examination revealed that they
      all had localized tenderness in the lateral and inferior part of the
      gastrocnemius muscle, with decreasing of skin temperature. The pulse of dorsalis
      pedis artery and the posterior tibial artery on affected limbs could be felt.
      Blood coagulation function and biochemical assay showed that D-dimer, fibrinogen
      degradation products, creatine kinase, or myoglobin markedly elevated. Magnetic
      resonance angiography revealed proximal peroneal artery stenosis. All patients
      were treated with intravenous thrombolysis, anticoagulation, vasodilation, and
      improving circulation therapy. RESULTS: The symptoms of lower limb swelling,
      pain, and fatigue were improved obviously in all patients after treatment. Blood
      coagulation function and biochemical assay showed D-dimer, fibrinogen degradation
      products, creatine kinase, or myoglobin were gradually reduced. The patients were
      discharged at 9-13 days after treatments, without recurrence during the follow-up
      of 1 year. CONCLUSION: Acute peroneal artery ischemia syndrome is a special type
      of acute lower limb ischemia, with the three symptoms of "peroneal artery blood
      supply zone pale/red + severe pain of the gastrocnemius muscle + acute drop foot"
      as the main characteristics and should be treated by early active anticoagulant
      and recanalization therapy.

PMID- 25591308
TI  - [Fabrication of pre-vascularized cell sheets based on rabbit bone marrow
      mesenchymal stem cells].
AB  - OBJECTIVE: To explore a new method of developing a pre-vascularized cell sheets.
      METHODS: Bone marrow mesenchymal stem cells (BMSCs) from 3-week-old Japanese
      white rabbits were harvested and cultured. Vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) were added into the culture
      medium to differentiate into endothelial like cells (ECs) from BMSCs
      (experimental group), and non-induced cells served as the control group. The cell
      morphology was observed; and the von Willebrand factor (vWF) and CD31
      immunofluorescent staining was used to identify the induced BMSCs. The 2nd
      generation BMSCs were seeded on a cell culture dish at a cell density of 9 x
      10(4) cells/cm2 and cultured for 14 days to form a thick cell sheet, and ECs from
      BMSCs were then seeded on the BMSCs sheet at a cell density of 5 x 10(4)
      cells/cm2 to develop pre-vascularized cell sheets and cultured for 3, 7, and 14
      days (group A); non-induced BMSCs sheet and only ECs from BMSCs were used as
      group B and group C, respectively. The CD31 immunofluorescent staining and
      histological analysis were performed to evaluate the pre-vascularized cell sheet.
      RESULTS: BMSCs changed from long fusiform to cobblestone-like morphology after
      induced by VEGF and bFGF. The expressions of CD31 and vWF were positive in
      experimental group, but were negative in control group, which suggested that
      BMSCs have the ability to differentiate into ECs under this condition. After the
      ECs were seeded on the BMSCs sheet, the ECs migrated and rearranged;
      intracellular vacuoles and networks were observed. Furthermore, immunofluorescent
      staining for CD31 also revealed a developing process of tube formation after the
      ECs were seeded on the BMSCs sheet. The histological evaluations indicated the
      microvessel lumen formed. However, no similar change was observed in groups B and
      C. CONCLUSION: BMSCs have the ability to differentiate into ECs after induced by
      VEGF and bFGF. ECs from BMSCs can develop into vascular network constructs when
      seeded on the BMSCs sheet, which provides a new method for engineering pre
      vascularized tissue construction.

PMID- 25591309
TI  - [Regulation of human bone marrow mesenchymal stem cells osteogenic and adipogenic
      differentiations by Wnt10b adenoviral vector in vitro].
AB  - OBJECTIVE: To investigate the regulation of human bone marrow mesenchymal stem
      cells (hBMSCs) osteogenic and adipogenic differentiations mediated by Wnt10b
      adenoviral vector in vitro. METHODS: The hBMSCs from ilial bone tissue in adults
      at passage 4 were infected by Wnt10b gene expression adenoviral vector (group A),
      Wnt10b-shRNA adenoviral vector (group B), and empty vector (group C), and non
      transfected hBMSCs served as the blank control group. Then the cells were
      cultured separately in the circumstance of osteogenic induction, adipogenic
      induction, and non-induction. The alkaline phosphatase (ALP) staining, alizarin
      red staining, and oil red O staining were used to detect the osteogenic and
      adipogenic differentiations; real-time fluorescent quantitative PCR and Western
      blot were used to analyze the expressions of osteoblast and adipocyte genes and
      proteins. RESULTS: The results of ALP staining were positive after osteogenic
      induction, group A showed strong staining, and group B showed the weakest
      staining. The results of alizarin red staining showed that there were a lot of
      patchy confluent brown mineralized nodules in group A; a few punctate brown
      mineralized nodules were seen in group B; and many punctuate brown mineralized
      nodules were found in groups C and D. The results of oil red O staining showed
      strong staining in groups B, C, and D after adipogenic induction, especially in
      group B; scattered or small clustered staining was observed in group A. The
      expressions of osteoblast genes and proteins were significantly higher in group A
      than groups B, C, and D, and in groups C and D than group B by real-time
      fluorescent quantitative PCR and Western blot test; however, the expressions of
      adipocyte genes and proteins showed a contrary tendency. CONCLUSION: The high
      level expression of Wnt10b can enhance osteogenic differentiation of hBMSCs, and
      the low level expression of Wnt10b can increase adipogenic differentiation of
      hBMSCs.

PMID- 25591310
TI  - [Study on gene transfection in bone marrow mesenchymal stem cells mediated by
      plasmid of bone morphogenetic protein 2 loaded lipopolysaccharide-amine
      nanopolymersomes].
AB  - OBJECTIVE: To evaluate the combination of lipopolysaccharide-amine
      nanopolymersomes (LNPs), as a gene vector, with target gene and the transfection
      in bone marrow mesenchymal stem cells (BMSCs) so as to provide a preliminary
      experiment basis for combination treatment of bone defect with gene therapy
      mediated by LNPs and stem cells. METHODS: Plasmid of bone morphogenetic protein 2
      (pBMP-2)-loaded LNPs (pLNPs) were prepared. The binding ability of pLNPs to pBMP
      2 was evaluated by a gel retardation experiment with different ratios of nitrogen
      to phosphorus elements (N/P). The morphology ofpLNPs (N/P = 60) was observed
      under transmission electron microscope (TEM) and atomic force microscope (AFM).
      The size and Zeta potential were measured by dynamic light scattering (DLS). The
      resistance of pLNPs against DNase I degradation over time was explored. The
      viability of BMSCs, transfection efficiency, and expression of target protein
      were investigated after transfection by pLNPs in vitro. RESULTS: At N/P >= 1.5,
      pLNPs could completely retard pBMP-2; at N/P of 60, pLNPs was uniform vesicular
      shape under AFM; TEM observation demonstrated that pLNPs were spherical nano
      vesicles with the diameter of (72.07 +/- 11.03) nm, DLS observation showed that
      the size of pLNPs was (123 +/- 6) nm and Zeta potential was 20 mV; pLNPs could
      completely resist DNase I degradation within 4 hours, and such protection
      capacity to pBMP-2 decreased slightly at 6 hours. The cell survival rate first
      increased and then decreased with the increase of N/P, and reached the maximum
      value at N/P of 45; the cytotoxicity was in grade I at N/P <= 90, which meant no
      toxicity for in vivo experiment. While the transfection efficiency of pLNPs
      increased with the increase of N/P, and reached the maximum value at N/P of 60.
      So it is comprehensively determined that the best N/P was 60. At 4 days,
      transfected BMSCs expressed BMP-2 continuously at a relatively high level at N/P
      of 60. CONCLUSION: LNPs can compress pBMP-2 effectively to form the nanovesicles
      complex, which protects the target gene against enzymolysis. LNPs has higher
      transfection efficiency and produces more amount of protein than polyethylenimine
      25k and Lipofectamine 2000.

PMID- 25591311
TI  - [Research development of diagnosis and treatment of meniscal root tears].
AB  - OBJECTIVE: To analyze the causes of meniscal root tears (MRTs), and to review the
      progress in its diagnosis and therapy. METHODS: The published literature about
      MRTs was extensively reviewed and summarized. RESULTS: MRTs can be divided into
      acute traumatic injuries and chronic degenerative injuries; MRI examination is an
      effective way to diagnose according to meniscal extrusion, ghost sign, and
      meniscal root linear defects. Conservative treatments are mainly performed for
      chronic MRTs; partial meniscectomy can obtain predictable improvement in
      symptoms. Acute MRTs can be treated by arthroscopic meniscus repair and
      reconstruction which can effectively restore meniscal root anatomy and function,
      and knee joint degeneration can be postponed. CONCLUSION: MRTs diagnosis relies
      on MRI, appropriate treatment plan should be made based on the specific
      circumstances of the patient after accurate diagnosis. Usually the satisfied
      short-term clinical results can be obtained, while the long-term results need
      more clinical evaluation.

PMID- 25591312
TI  - [Research progress of self-assembling peptide nanofiber scaffold for bone
      repair].
AB  - OBJECTIVE: To review the biological characteristics of self-assembling peptide
      nanofiber scaffold (SAPNS) and its potential to induce bone repair. METHODS: The
      literature regarding SAPNS and its application in bone repair was extensively
      analyzed and reviewed. RESULTS: SAPNS is derived from natural amino acids, and
      has the properties of good biocompatibility and non-toxic degradation products.
      Their microenvironment highly mimics the natural extracellular matrix, and
      controlled release of growth factors as well as modification with functional
      motifs can substantially improve their bioactivity. Many studies on cell
      composite culture and bone defect repair of animal models reveal that SAPNS has
      the ability to promote the function of bone cells (e.g. adherence, proliferation,
      and differentiation) in vitro, and enhance new bone tissue formation in vivo.
      CONCLUSION: SAPNS may be an ideal material for bone repair, but its biologically
      mechanical properties need further improvement.

PMID- 25591313
TI  - [Application of silk fibroin scaffold in bone tissue engineering].
AB  - OBJECTIVE: To review the application of silk fibroin scaffold in bone tissue
      engineering. METHODS: The related literature about the application of silk
      fibroin scaffold in bone tissue engineering was reviewed, analyzed, and
      summarized. RESULTS: Silk fibroin can be manufactured into many types, such as
      hydrogel, film, nano-fiber, and three-dimensional scaffold, which have superior
      biocompatibility, slow biodegradability, nontoxic degradation products, and
      excellent mechanical strength. Meanwhile these silk fibroin biomaterials can be
      chemically modified and can be used to carry stem cells, growth factors, and
      compound inorganic matter. CONCLUSION: Silk fibroin scaffolds can be widely used
      in bone tissue engineering. But it still needs further study to prepare the
      scaffold in accordance with the requirement of tissue engineering.

PMID- 25591314
TI  - [Application of platelet-rich plasma in clinical orthopedics].
AB  - OBJECTIVE: To summarize the application status and progress of platelet-rich
      plasma (PRP) in clinical orthopedics. METHODS: The recent related literature
      concerning the application of PRP in clinical orthopedics was extensively
      reviewed and analyzed. RESULTS: Recently, a large number of clinical studies on
      PRP have been carried out, which are applied in bone defects or nonunion, spinal
      fusion, osteoarthritis and cartilage injuries, ligament reconstruction, muscle
      strain, tendon terminal diseases, and a variety of acute and chronic soft tissue
      injuries. Some results show certain effectiveness, while others demonstrate
      invalid. CONCLUSION: Easily drawing, achieving autologous transplantation, and
      the biological repair potential of the musculoskeletal tissues make PRP to be
      widely used in clinical orthopedics. However, there are still no uniform
      standards accepted and reliable clinical guidelines about the application of PRP.
      Furthermore, a variety of PRP products and their respective indications are also
      different. The clinical evidences with the greater sample size and higher quality
      are still needed to further support the safety and effectiveness of PRP in
      clinical orthopedics.

PMID- 25591315
TI  - Politics & policy: immigration order may expand health coverage.

PMID- 25591316
TI  - Reform: open enrollment going well, so far.

PMID- 25591317
TI  - Supply chain: hospital recall management criticized.

PMID- 25591318
TI  - Growing community-based doctors.

PMID- 25591319
TI  - Were patients really sicker?

PMID- 25591320
TI  - Clinical pathways can lead to better cancer care.

PMID- 25591321
TI  - Too many healthcare leaders still aren't planning for the 'future state'.

PMID- 25591323
TI  - If you've seen one narrow network, you've seen one.

PMID- 25591322
TI  - Autonomy for nursing home residents.

PMID- 25591324
TI  - Evaluation of certain veterinary drug residues in food. Seventy-eighth report of
      the Joint FAO/WHO Expert Committee on Food Additives.
AB  - This report represents the conclusions of a Joint FAO/WHO Expert Committee
      convened to evaluate the safety of residues of certain veterinary drugs in food
      and to recommend maximum levels for such residues of food. The first part of the
      report considers general principles regarding the evaluation of residues of
      veterinary drugs within the terms of reference of the Joint FAO/WHO Expert
      Committee on Food Additives (JECFA), including extrapolation of maximum residue
      limits (MRLs) to minor species, MRLs for veterinary drug residues in honey, MRLs
      relating to fish and fish species, dietary exposure assessment methodologies, the
      decision-tree approach to the evaluation of residues of veterinary drugs and
      guidance for JECFA experts. Summaries follow of the Committee's evaluations of
      toxicology and residue data on a variety of veterinary drugs: two anthelminthic
      agents (derquantel, monepantel), three antiparasitic agents (emanectin benzoate,
      ivermectin, lasalocid sodium), one antibacterial, antifungal and anthelminthic
      agent (gentian violet), a production aid (recombinant bovine somatotropins) and
      an adrenoceptor agonist and growth promoter (zilpaterol hydorchloride). Annexed
      to the report is a summary of the Committee's recommendations on these drugs,
      including acceptable daily intakes (ADIs)) and proposed MRLs.

PMID- 25591326
TI  - Frequency of Ggamma-globin promoter -158 (C>T) XmnI polymorphism in patients with
      homozygous/compound heterozygous beta thalassaemia.
AB  - BACKGROUND: Response to hydroxyurea therapy in homozygous or compound
      heterozygous beta thalassaemia (BT) has been reported as more favourable in the
      presence of XmnI polymorphism. The prevalence of XmnI polymorphism may vary with
      BT phenotypes and genotypes, and differs geographically in distribution.
      Prevalence of XmnI polymorphism is not known in northern Pakistan. OBJECTIVE: To
      determine the frequency of Ggamma-globin promoter -158 (C>T) XmnI polymorphism
      (XmnI polymorphism) in patients with homozygous or compound heterozygous beta
      thalassaemia. MATERIALS: Polymerase chain reaction (PCR) for common beta
      thalassaemia mutations and Ggamma-globin promoter -158 (C>T) XmnI polymorphism
      was performed on 107 blood samples of transfusion dependent beta thalassaemia
      (BT) patients in Pakistan. One hundred samples of unrelated BT traits and 94
      samples of healthy subjects as controls were also analysed for BT mutations and
      XmnI polymorphism. RESULTS: Out of 301 DNA samples, XmnI polymorphism was
      detected in 71(24%); in normal controls, XmnI polymorphism was detected in 34/94
      (36%) subjects; while in homozygous/compound heterozygous BT, it was detected in
      14/107(13%) patients (Fisher's exact test, p=.0002). In heterozygous BT group,
      XmnI polymorphism was detected in 23/100 subjects (Fisher's exact test, p=.03
      with normal controls, and p=.049 with homozygous/compound heterozygous BT). The
      most common BT genotype was Frame Shift (Fr) 8-9/Fr 8-9, and none of the patients
      with this genotype had XmnI polymorphism. The second most common genotype was
      IVSI-5/IVSI-5; 4/26 (15%). Cases with this genotype had XmnI polymorphism.
      CONCLUSION: XmnI polymorphism in homozygous/compound heterozygous BT group is
      13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI
      5.

PMID- 25591325
TI  - YersiniaBase: a genomic resource and analysis platform for comparative analysis
      of Yersinia.
AB  - BACKGROUND: Yersinia is a Gram-negative bacteria that includes serious pathogens
      such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis,
      Yersinia enterocolitica. The remaining species are generally considered non
      pathogenic to humans, although there is evidence that at least some of these
      species can cause occasional infections using distinct mechanisms from the more
      pathogenic species. With the advances in sequencing technologies, many genomes of
      Yersinia have been sequenced. However, there is currently no specialized platform
      to hold the rapidly-growing Yersinia genomic data and to provide analysis tools
      particularly for comparative analyses, which are required to provide improved
      insights into their biology, evolution and pathogenicity. DESCRIPTION: To
      facilitate the ongoing and future research of Yersinia, especially those
      generally considered non-pathogenic species, a well-defined repository and
      analysis platform is needed to hold the Yersinia genomic data and analysis tools
      for the Yersinia research community. Hence, we have developed the YersiniaBase, a
      robust and user-friendly Yersinia resource and analysis platform for the analysis
      of Yersinia genomic data. YersiniaBase has a total of twelve species and 232
      genome sequences, of which the majority are Yersinia pestis. In order to smooth
      the process of searching genomic data in a large database, we implemented an
      Asynchronous JavaScript and XML (AJAX)-based real-time searching system in
      YersiniaBase. Besides incorporating existing tools, which include JavaScript
      based genome browser (JBrowse) and Basic Local Alignment Search Tool (BLAST),
      YersiniaBase also has in-house developed tools: (1) Pairwise Genome Comparison
      tool (PGC) for comparing two user-selected genomes; (2) Pathogenomics Profiling
      Tool (PathoProT) for comparative pathogenomics analysis of Yersinia genomes; (3)
      YersiniaTree for constructing phylogenetic tree of Yersinia. We ran analyses
      based on the tools and genomic data in YersiniaBase and the preliminary results
      showed differences in virulence genes found in Yersinia pestis and Yersinia
      pseudotuberculosis compared to other Yersinia species, and differences between
      Yersinia enterocolitica subsp. enterocolitica and Yersinia enterocolitica subsp.
      palearctica. CONCLUSIONS: YersiniaBase offers free access to wide range of
      genomic data and analysis tools for the analysis of Yersinia. YersiniaBase can be
      accessed at http://yersinia.um.edu.my .

PMID- 25591327
TI  - Stereotactic radiotherapy in the treatment of primary bronchial carcinoid tumor.

PMID- 25591328
TI  - Retraction: Efficient quantum transmission in multiple-source networks.

PMID- 25591329
TI  - Mutational Analysis of Exostosin 1 and 2 Genes in Multiple Osteochondroma.

PMID- 25591330
TI  - Communication: theoretical prediction of free-energy landscapes for complex self
      assembly.
AB  - We present a technique for calculating free-energy profiles for the nucleation of
      multicomponent structures that contain as many species as building blocks. We
      find that a key factor is the topology of the graph describing the connectivity
      of the target assembly. By considering the designed interactions separately from
      weaker, incidental interactions, our approach yields predictions for the
      equilibrium yield and nucleation barriers. These predictions are in good
      agreement with corresponding Monte Carlo simulations. We show that a few
      fundamental properties of the connectivity graph determine the most prominent
      features of the assembly thermodynamics. Surprisingly, we find that
      polydispersity in the strengths of the designed interactions stabilizes
      intermediate structures and can be used to sculpt the free-energy landscape for
      self-assembly. Finally, we demonstrate that weak incidental interactions can
      preclude assembly at equilibrium due to the combinatorial possibilities for
      incorrect association. 

PMID- 25591331
TI  - Communication: generalization of Koopmans' theorem to optical transitions in the
      Hubbard model of graphene nanodots.
AB  - Koopmans' theorem implies that the Hartree-Fock quasiparticle gap in a closed
      shell system is equal to its single-particle energy gap. In this work, the
      theorem is generalized to optical transitions in the Hubbard model of graphene
      nanodots. Based on systematic configuration interaction calculations, it is
      proposed that the optical gap of a closed-shell graphene system within the
      Hubbard model is equal to its tight-binding single-particle energy gap in the
      absence of electron correlation. In these systems, the quasiparticle energy gap
      and exciton binding energy are found to be dominated by the long-range Coulomb
      interaction, and thus, both become small when only on-site Hubbard interactions
      are present. Moreover, the contributions of the quasiparticle and excitonic
      effects to the optical gap are revealed to nearly cancel each other, which
      results in an unexpected overlap of the optical and single-particle gaps of the
      graphene systems. 

PMID- 25591332
TI  - Generalized Metropolis acceptance criterion for hybrid non-equilibrium molecular
      dynamics-Monte Carlo simulations.
AB  - A family of hybrid simulation methods that combines the advantages of Monte Carlo
      (MC) with the strengths of classical molecular dynamics (MD) consists in carrying
      out short non-equilibrium MD (neMD) trajectories to generate new configurations
      that are subsequently accepted or rejected via an MC process. In the simplest
      case where a deterministic dynamic propagator is used to generate the neMD
      trajectories, the familiar Metropolis acceptance criterion based on the change in
      the total energy DeltaE, min[1, exp{-betaDeltaE}], guarantees that the hybrid
      algorithm will yield the equilibrium Boltzmann distribution. However, the
      functional form of the acceptance probability is more complex when the non
      equilibrium switching process is generated via a non-deterministic stochastic
      dissipative propagator coupled to a heat bath. Here, we clarify the conditions
      under which the Metropolis criterion remains valid to rigorously yield a proper
      equilibrium Boltzmann distribution within hybrid neMD-MC algorithm.

PMID- 25591333
TI  - Configuration interaction singles natural orbitals: an orbital basis for an
      efficient and size intensive multireference description of electronic excited
      states.
AB  - Multireference quantum chemical methods, such as the complete active space self
      consistent field (CASSCF) method, have long been the state of the art for
      computing regions of potential energy surfaces (PESs) where complex,
      multiconfigurational wavefunctions are required, such as near conical
      intersections. Herein, we present a computationally efficient alternative to the
      widely used CASSCF method based on a complete active space configuration
      interaction (CASCI) expansion built from the state-averaged natural orbitals of
      configuration interaction singles calculations (CISNOs). This CISNO-CASCI
      approach is shown to predict vertical excitation energies of molecules with
      closed-shell ground states similar to those predicted by state averaged (SA)
      CASSCF in many cases and to provide an excellent reference for a perturbative
      treatment of dynamic electron correlation. Absolute energies computed at the
      CISNO-CASCI level are found to be variationally superior, on average, to other
      CASCI methods. Unlike SA-CASSCF, CISNO-CASCI provides vertical excitation
      energies which are both size intensive and size consistent, thus suggesting that
      CISNO-CASCI would be preferable to SA-CASSCF for the study of systems with
      multiple excitable centers. The fact that SA-CASSCF and some other CASCI methods
      do not provide a size intensive/consistent description of excited states is
      attributed to changes in the orbitals that occur upon introduction of non
      interacting subsystems. Finally, CISNO-CASCI is found to provide a suitable
      description of the PES surrounding a biradicaloid conical intersection in
      ethylene. 

PMID- 25591334
TI  - An efficient dissipative particle dynamics-based algorithm for simulating
      electrolyte solutions.
AB  - We propose an efficient simulation algorithm based on the dissipative particle
      dynamics (DPD) method for studying electrohydrodynamic phenomena in electrolyte
      fluids. The fluid flow is mimicked with DPD particles while the evolution of the
      concentration of the ionic species is described using Brownian pseudo particles.
      The method is designed especially for systems with high salt concentrations, as
      explicit treatment of the salt ions becomes computationally expensive. For
      illustration, we apply the method to electro-osmotic flow over patterned,
      superhydrophobic surfaces. The results are in good agreement with recent
      theoretical predictions. 

PMID- 25591335
TI  - Restricted Hartree Fock using complex-valued orbitals: a long-known but neglected
      tool in electronic structure theory.
AB  - Restricted Hartree Fock using complex-valued orbitals (cRHF) is studied. We
      introduce an orbital pairing theorem, with which we obtain a concise connection
      between cRHF and real-valued RHF, and use it to uncover the close relationship
      between cRHF, unrestricted Hartree Fock, and generalized valence bond perfect
      pairing. This enables an intuition for cRHF, contrasting with the generally
      unintuitive nature of complex orbitals. We also describe an efficient computer
      implementation of cRHF and its corresponding stability analysis. By applying cRHF
      to the Be + H2 insertion reaction, a Woodward-Hoffmann violating reaction, and a
      symmetry-driven conical intersection, we demonstrate in genuine molecular systems
      that cRHF is capable of removing certain potential energy surface singularities
      that plague real-valued RHF and related methods. This complements earlier work
      that showed this capability in a model system. We also describe how cRHF is the
      preferred RHF method for certain radicaloid systems like singlet oxygen and
      antiaromatic molecules. For singlet O2, we show that standard methods fail even
      at the equilibrium geometry. An implication of this work is that, regardless of
      their individual efficacies, cRHF solutions to the HF equations are fairly
      commonplace. 

PMID- 25591336
TI  - Tensor decomposition techniques in the solution of vibrational coupled cluster
      response theory eigenvalue equations.
AB  - We show how the eigenvalue equations of vibrational coupled cluster response
      theory can be solved using a subspace projection method with Davidson update,
      where basis vectors are stacked tensors decomposed into canonical (CP,
      Candecomp/Parafac) form. In each update step, new vectors are first
      orthogonalized to old vectors, followed by a tensor decomposition to a prescribed
      threshold TCP. The algorithm can provide excitation energies and eigenvectors of
      similar accuracy as a full vector approach and with only a very modest increase
      in the number of vectors required for convergence. The algorithm is illustrated
      with sample calculations for formaldehyde, 1,2,5-thiadiazole, and water. Analysis
      of the formaldehyde and thiadiazole calculations illustrate a number of
      interesting features of the algorithm. For example, the tensor decomposition
      threshold is optimally put to rather loose values, such as TCP = 10(-2). With
      such thresholds for the tensor decompositions, the original eigenvalue equations
      can still be solved accurately. It is thus possible to directly calculate
      vibrational wave functions in tensor decomposed format. 

PMID- 25591337
TI  - Nudged-elastic band method with two climbing images: finding transition states in
      complex energy landscapes.
AB  - The nudged-elastic band (NEB) method is modified with concomitant two climbing
      images (C2-NEB) to find a transition state (TS) in complex energy landscapes,
      such as those with a serpentine minimal energy path (MEP). If a single climbing
      image (C1-NEB) successfully finds the TS, then C2-NEB finds it too. However,
      improved stability of C2-NEB makes it suitable for more complex cases, where C1
      NEB misses the TS because the MEP and NEB directions near the saddle point are
      different. Generally, C2-NEB not only finds the TS, but also guarantees, by
      construction, that the climbing images approach it from the opposite sides along
      the MEP. In addition, C2-NEB provides an accuracy estimate from the three images:
      the highest-energy one and its climbing neighbors. C2-NEB is suitable for fixed
      cell NEB and the generalized solid-state NEB. 

PMID- 25591338
TI  - A general non-Abelian density matrix renormalization group algorithm with
      application to the C2 dimer.
AB  - We extend our previous work [S. Sharma and G. K.-L. Chan, J. Chem. Phys. 136,
      124121 (2012)], which described a spin-adapted (SU(2) symmetry) density matrix
      renormalization group algorithm, to additionally utilize general non-Abelian
      point group symmetries. A key strength of the present formulation is that the
      requisite tensor operators are not hard-coded for each symmetry group, but are
      instead generated on the fly using the appropriate Clebsch-Gordan coefficients.
      This allows our single implementation to easily enable (or disable) any non
      Abelian point group symmetry (including SU(2) spin symmetry). We use our
      implementation to compute the ground state potential energy curve of the C2 dimer
      in the cc-pVQZ basis set (with a frozen-core), corresponding to a Hilbert space
      dimension of 10(12) many-body states. While our calculated energy lies within the
      0.3 mEh error bound of previous initiator full configuration interaction quantum
      Monte Carlo and correlation energy extrapolation by intrinsic scaling
      calculations, our estimated residual error is only 0.01 mEh, much more accurate
      than these previous estimates. Due to the additional efficiency afforded by the
      algorithm, the excitation energies (Te) of eight lowest lying excited states:
      a(3)Piu, b(3)Sigmag (-), A(1)Piu, c(3)Sigmau (+), B(1)Deltag, B(') (1)Sigmag (+),
      d(3)Pig, and C(1)Pig are calculated, which agree with experimentally derived
      values to better than 0.06 eV. In addition, we also compute the potential energy
      curves of twelve states: the three lowest levels for each of the irreducible
      representations (1)Sigmag (+), (1)Sigmau (+), (1)Sigmag (-), and (1)Sigmau (-),
      to an estimated accuracy of 0.1 mEh of the exact result in this basis. 

PMID- 25591339
TI  - Brownian dynamics simulations of coagulation of dilute uniform and anisotropic
      particles under shear flow spanning low to high Peclet numbers.
AB  - Brownian dynamics simulations are performed to study the binding kinetics in the
      dilute-sphere limit by considering interactions of two spheres under shear flow
      across the entire range of Peclet numbers, spanning both perikinetic (diffusion
      controlled) and orthokinetic (flow-controlled) coagulation regimes. The dilute
      regime is attained by carrying out two-sphere simulations in periodic boxes of
      different sizes and aspect ratios and extrapolating toward the infinite box
      limit. Effects of particle type (Janus and isotropic particles), shear rate,
      hydrodynamic interactions, and inter-particle potential are explored. We find
      that rectangular boxes with appropriate aspect ratios overcome a particle "shadow
      effect" that cannot be overcome with cubic boxes unless huge boxes are used. With
      rectangular boxes, we obtain converged binding kinetics for the whole Peclet
      number range, while cubic boxes of increasing size allow converged results only
      in the absence of flow. We consider the effect of binding both in a secondary
      minimum controlled by a combination of electrostatic repulsion and depletion
      attraction, as well as in a primary minimum governed by induced-dipole
      attraction. Results are computed using both realistic interaction potentials and
      by replacing the potential with a simple cutoff gap distance at which binding is
      deemed to occur. Results agree with several existing reports including
      Smoluchowski predictions in the zero- and infinite-shear-rate limits, and high-Pe
      perturbation results of Feke and Schowalter [J. Fluid Mech. 133, 17-35 (1983)] at
      Peclet numbers (Pe) above 100. Finally, we compute binding times for anisotropic
      Janus particles which have both repulsive and attractive faces, for a wide range
      of Pe number. 

PMID- 25591340
TI  - The fast multipole method and point dipole moment polarizable force fields.
AB  - We present an implementation of the fast multipole method for computing Coulombic
      electrostatic and polarization forces from polarizable force-fields based on
      induced point dipole moments. We demonstrate the expected O(N) scaling of that
      approach by performing single energy point calculations on hexamer protein
      subunits of the mature HIV-1 capsid. We also show the long time energy
      conservation in molecular dynamics at the nanosecond scale by performing
      simulations of a protein complex embedded in a coarse-grained solvent using a
      standard integrator and a multiple time step integrator. Our tests show the
      applicability of fast multipole method combined with state-of-the-art chemical
      models in molecular dynamical systems. 

PMID- 25591341
TI  - Thermal equilibrium properties of surface hopping with an implicit Langevin bath.
AB  - The ability of fewest switches surface hopping (FSSH) approach, where the
      classical degrees of freedom are coupled to an implicit Langevin bath, to
      establish and maintain an appropriate thermal equilibrium was evaluated in the
      context of a three site model for electron transfer. The electron transfer model
      consisted of three coupled diabatic states that each depends harmonically on the
      collective bath coordinate. This results in three states with increasing energy
      in the adiabatic representation. The adiabatic populations and distributions of
      the collective solvent coordinate were monitored during the course of 250 ns FSSH
      Langevin (FSSH-L) simulations performed at a broad range of temperatures and for
      three different nonadiabatic coupling strengths. The agreement between the FSSH-L
      simulations and numerically exact results for the adiabatic population ratios and
      solvent coordinate distributions was generally favorable. The FSSH-L method
      produces a correct Boltzmann distribution of the solvent coordinate on each of
      the adiabats, but the integrated populations are slightly incorrect because FSSH
      does not rigorously obey detailed balance. The overall agreement is better at
      high temperatures and for high nonadiabatic coupling, which agrees with a
      previously reported analytical and simulation analysis [J. R. Schmidt, P. V.
      Parandekar, and J. C. Tully, J. Chem. Phys. 129, 044104 (2008)] on a two-level
      system coupled to a classical bath. 

PMID- 25591342
TI  - On performance measures for infinite swapping Monte Carlo methods.
AB  - We introduce and illustrate a number of performance measures for rare-event
      sampling methods. These measures are designed to be of use in a variety of
      expanded ensemble techniques including parallel tempering as well as infinite and
      partial infinite swapping approaches. Using a variety of selected applications,
      we address questions concerning the variation of sampling performance with
      respect to key computational ensemble parameters. 

PMID- 25591343
TI  - Nonperturbative spin-boson and spin-spin dynamics and nonlinear Fano
      interferences: a unified dissipaton theory based study.
AB  - We consider the hybrid system-bath dynamics, based on the Yan's dissipaton
      formalism [Y. J. Yan, J. Chem. Phys. 140, 054105 (2014)]. This theory provides a
      unified quasi-particle treatment on three distinct classes of quantum bath,
      coupled nonperturbatively to arbitrary quantum systems. In this work, to study
      the entangled system and bath polarization and nonlinear Fano interference, we
      incorporate further the time-dependent light field, which interacts with both the
      molecular system and the collective bath dipoles directly. Numerical
      demonstrations are carried out on a two-level system, with comparison between
      phonon and exciton baths, in both linear and nonlinear Fano interference regimes.

PMID- 25591344
TI  - An adaptive multi-level simulation algorithm for stochastic biological systems.
AB  - Discrete-state, continuous-time Markov models are widely used in the modeling of
      biochemical reaction networks. Their complexity often precludes analytic
      solution, and we rely on stochastic simulation algorithms (SSA) to estimate
      system statistics. The Gillespie algorithm is exact, but computationally costly
      as it simulates every single reaction. As such, approximate stochastic simulation
      algorithms such as the tau-leap algorithm are often used. Potentially
      computationally more efficient, the system statistics generated suffer from
      significant bias unless tau is relatively small, in which case the computational
      time can be comparable to that of the Gillespie algorithm. The multi-level method
      [Anderson and Higham, "Multi-level Monte Carlo for continuous time Markov chains,
      with applications in biochemical kinetics," SIAM Multiscale Model. Simul. 10(1),
      146-179 (2012)] tackles this problem. A base estimator is computed using many
      (cheap) sample paths at low accuracy. The bias inherent in this estimator is then
      reduced using a number of corrections. Each correction term is estimated using a
      collection of paired sample paths where one path of each pair is generated at a
      higher accuracy compared to the other (and so more expensive). By sharing random
      variables between these paired paths, the variance of each correction estimator
      can be reduced. This renders the multi-level method very efficient as only a
      relatively small number of paired paths are required to calculate each correction
      term. In the original multi-level method, each sample path is simulated using the
      tau-leap algorithm with a fixed value of tau. This approach can result in poor
      performance when the reaction activity of a system changes substantially over the
      timescale of interest. By introducing a novel adaptive time-stepping approach
      where tau is chosen according to the stochastic behaviour of each sample path, we
      extend the applicability of the multi-level method to such cases. We demonstrate
      the efficiency of our method using a number of examples. 

PMID- 25591345
TI  - A pure-sampling quantum Monte Carlo algorithm.
AB  - The objective of pure-sampling quantum Monte Carlo is to calculate physical
      properties that are independent of the importance sampling function being
      employed in the calculation, save for the mismatch of its nodal hypersurface with
      that of the exact wave function. To achieve this objective, we report a pure
      sampling algorithm that combines features of forward walking methods of pure
      sampling and reptation quantum Monte Carlo (RQMC). The new algorithm accurately
      samples properties from the mixed and pure distributions simultaneously in runs
      performed at a single set of time-steps, over which extrapolation to zero time
      step is performed. In a detailed comparison, we found RQMC to be less efficient.
      It requires different sets of time-steps to accurately determine the energy and
      other properties, such as the dipole moment. We implement our algorithm by
      systematically increasing an algorithmic parameter until the properties converge
      to statistically equivalent values. As a proof in principle, we calculated the
      fixed-node energy, static alpha polarizability, and other one-electron
      expectation values for the ground-states of LiH and water molecules. These
      quantities are free from importance sampling bias, population control bias, time
      step bias, extrapolation-model bias, and the finite-field approximation. We found
      excellent agreement with the accepted values for the energy and a variety of
      other properties for those systems. 

PMID- 25591347
TI  - Theoretical study of thorium monoxide for the electron electric dipole moment
      search: electronic properties of H(3)Delta(1) in ThO.
AB  - Recently, improved limits on the electron electric dipole moment, and
      dimensionless constant, kT,P, characterizing the strength of the T,P-odd
      pseudoscalar-scalar electron-nucleus neutral current interaction in the
      H(3)Delta1 state of ThO molecule were obtained by the ACME collaboration [J.
      Baron et al., Science 343, 269 (2014)]. The interpretation of the experiment in
      terms of these fundamental quantities is based on the results of theoretical
      study of appropriate ThO characteristics, the effective electric field acting on
      electron, Eeff, and a parameter of the T,P-odd pseudoscalar-scalar interaction,
      WT,P, given in Skripnikov et al. [J. Chem. Phys. 139, 221103 (2013)] by St.
      Petersburg group. To reduce the uncertainties of the given limits, we report
      improved calculations of the molecular state-specific quantities Eeff, 81.5
      GV/cm, and WT,P, 112 kHz, with the uncertainty within 7% of the magnitudes. Thus,
      the values recommended to use for the upper limits of the quantities are 75.8
      GV/cm and 104 kHz, correspondingly. The hyperfine structure constant, molecule
      frame dipole moment of the H(3)Delta1 state, and the H(3)Delta1 -> X(1)Sigma(+)
      transition energy which, in general, can serve as a measure of reliability of the
      obtained Eeff and WT,P values are also calculated. In addition, we report the
      first calculation of g-factor for the H(3)Delta1 state of ThO. The results are
      compared to the earlier experimental and theoretical studies, and a detailed
      analysis of uncertainties of the calculations is given. 

PMID- 25591346
TI  - Stochastic Liouville equations for femtosecond stimulated Raman spectroscopy.
AB  - Electron and vibrational dynamics of molecules are commonly studied by subjecting
      them to two interactions with a fast actinic pulse that prepares them in a
      nonstationary state and after a variable delay period T, probing them with a
      Raman process induced by a combination of a broadband and a narrowband pulse.
      This technique, known as femtosecond stimulated Raman spectroscopy (FSRS), can
      effectively probe time resolved vibrational resonances. We show how FSRS signals
      can be modeled and interpreted using the stochastic Liouville equations (SLE),
      originally developed for NMR lineshapes. The SLE provide a convenient simulation
      protocol that can describe complex dynamics caused by coupling to collective bath
      coordinates at much lower cost than a full dynamical simulation. The origin of
      the dispersive features that appear when there is no separation of timescales
      between vibrational variations and the dephasing time is clarified. 

PMID- 25591348
TI  - New XDM-corrected potential energy surfaces for Ar-NO(X(2)Pi): a comparison with
      CCSD(T) calculations and experiments.
AB  - We report new potential energy surfaces for the ground state Ar-NO(X(2)Pi) van
      der Waals system calculated using the unrestricted Hartree-Fock (UHF) method with
      the addition of the Becke-Roussel correlation functional and exchange-hole dipole
      moment dispersion correction (XDM). We compare UHFBR-XDM surfaces and those
      previously reported by Alexander from coupled cluster CCSD(T) calculations [J.
      Chem. Phys. 111, 7426 (1999)]. The bound states of Ar-NO have been investigated
      with these new UHFBR-XDM surfaces, including relative energy-level spacing,
      adiabatic bender states and wave functions, and spectroscopic data. These results
      have been found to be in good agreement with calculations based on the CCSD(T)
      PESs. These new PESs are used to investigate the inelastic scattering of NO(X) by
      Ar. Full close-coupling integral cross sections at collision energies of 442 cm(
      1), 1774 cm(-1) and differential cross sections at collision energy of 530 cm(-1)
      were determined for transitions out of the lowest NO(X) rotational level (j =
      omega = 1/2,f). These cross sections are in good agreement with those calculated
      with CCSD(T) and accordingly in good agreement with the most recent initial and
      final state resolved experimental data. The UHFBR-XDM scheme yields high-quality
      potential surfaces with computational cost comparable to the Hartree-Fock method
      and our results may serve as a benchmark for application of this scheme to
      collisions between larger molecules. 

PMID- 25591349
TI  - An accurate potential energy surface for the F + H2 -> HF + H reaction by the
      coupled-cluster method.
AB  - A three dimensional potential energy surface for the F + H2 -> HF + H reaction
      has been computed by the spin unrestricted coupled cluster method with singles,
      doubles, triples, and perturbative quadruples [UCCSDT(2)Q] using the augmented
      correlation-consistent polarised valence quadruple zeta basis set for the
      fluorine atom and the correlation-consistent polarised valence quadruple zeta
      basis set for the hydrogen atom. All the calculations are based on the restricted
      open-shell Hartree-Fock orbitals, together with the frozen core approximations,
      and the UCCSD(T)/complete basis set (CBS) correction term was included. The
      global potential energy surface was calculated by fitting the sampled ab initio
      points without any scaling factor for the correlation energy part using a neutral
      network function method. Extensive dynamics calculations have been carried out on
      the potential energy surface. The reaction rate constants, integral cross
      sections, product rotational states distribution, and forward and backward
      scattering as a function of collision energy of the F + HD -> HF + D, F + HD ->
      DF + H, and F + H2 reaction, were calculated by the time-independent quantum
      dynamics scattering theory using the new surface. The satisfactory agreement with
      the reported experimental observations previously demonstrates the accuracy of
      the new potential energy surface. 

PMID- 25591350
TI  - Low-temperature D(+) + H2 reaction: a time-dependent coupled wave-packet study in
      hyperspherical coordinates.
AB  - A recently proposed coupled three-dimensional time-dependent wave-packet
      formalism in hyperspherical coordinates is shown to yield accurate results for
      the reactive non-charge transfer process in the title system at collision
      energies as low as 100 K, where the lowest sheet of the accurate double many body
      expansion form for the singlet H3 (+) is used. The results are compared with
      available experimental data as well as time-independent calculations, and the
      agreement shown to be generally good. 

PMID- 25591351
TI  - Solvatochromism of 9,10-phenanthrenequinone: an electronic and resonance Raman
      spectroscopic study.
AB  - Solvent effects play a vital role in various chemical, physical, and biological
      processes. To gain a fundamental understanding of the solute-solvent interactions
      and their implications on the energy level re-ordering and structure, UV-VIS
      absorption, resonance Raman spectroscopic, and density functional theory
      calculation studies on 9,10-phenanthrenequinone (PQ) in different solvents of
      diverse solvent polarity has been carried out. The solvatochromic analysis of the
      absorption spectra of PQ in protic dipolar solvents suggests that the longest (1n
      pi(1)*; S1 state) and the shorter (1pi-pi(1)*; S2 state) wavelength band
      undergoes a hypsochromic and bathochromic shift due to intermolecular hydrogen
      bond weakening and strengthening, respectively. It also indicates that hydrogen
      bonding plays a major role in the differential solvation of the S2 state relative
      to the ground state. Raman excitation profiles of PQ (400-1800 cm(-1)) in various
      solvents followed their corresponding absorption spectra therefore the
      enhancements on resonant excitation are from single-state rather than mixed
      states. The hyperchromism of the longer wavelength band is attributed to
      intensity borrowing from the nearby allowed electronic transition through
      vibronic coupling. Computational calculation with C2nu symmetry constraint on the
      S2 state resulted in an imaginary frequency along the low-frequency out-of-plane
      torsional modes involving the C=O site and therefore, we hypothesize that this
      mode could be involved in the vibronic coupling. 

PMID- 25591352
TI  - Unexpected methyl migrations of ethanol dimer under synchrotron VUV radiation.
AB  - While methyl transfer is well known to occur in the enzyme- and metal-catalyzed
      reactions, the methyl transfer in the metal-free organic molecules induced by the
      photon ionization has been less concerned. Herein, vacuum ultraviolet single
      photon ionization and dissociation of ethanol dimer are investigated with
      synchrotron radiation photoionization mass spectroscopy and theoretical methods.
      Besides the protonated clusters cation (C2H5OH)?H(+) (m/z = 47) and the beta
      carbon-carbon bond cleavage fragment CH2O?(C2H5OH)H(+) (m/z = 77), the measured
      mass spectra revealed that a new fragment (C2H5OH)?(CH3)(+) (m/z = 61) appeared
      at the photon energy of 12.1 and 15.0 eV, where the neutral dimer could be
      vertically ionized to higher ionic state. Thereafter, the generated carbonium
      ions are followed by a Wagner-Meerwein rearrangement and then dissociate to
      produce this new fragment, which is considered to generate after surmounting a
      few barriers including intra- and inter-molecular methyl migrations by the aid of
      theoretical calculations. The appearance energy of this new fragment is measured
      as 11.55 +/- 0.05 eV by scanning photoionization efficiency curve. While the
      signal intensity of fragment m/z = 61 starts to increase, the fragments m/z = 47
      and 77 tend to slowly incline around 11.55 eV photon energy. This suggests that
      the additional fragment channels other than (C2H5OH)?H(+) and CH2O?(C2H5OH)H(+)
      have also been opened, which consume some dimer cations. The present report
      provides a clear description of the photoionization and dissociation processes of
      the ethanol dimer in the range of the photon energy 12-15 eV.

PMID- 25591353
TI  - Optimal control of a Cope rearrangement by coupling the reaction path to a
      dissipative bath or a second active mode.
AB  - We compare the strategy found by the optimal control theory in a complex
      molecular system according to the active subspace coupled to the field. The model
      is the isomerization during a Cope rearrangement of Thiele's ester that is the
      most stable dimer obtained by the dimerization of methyl
      cyclopentadienenylcarboxylate. The crudest partitioning consists in retaining in
      the active space only the reaction coordinate, coupled to a dissipative bath of
      harmonic oscillators which are not coupled to the field. The control then fights
      against dissipation by accelerating the passage across the transition region
      which is very wide and flat in a Cope reaction. This mechanism has been observed
      in our previous simulations [Chenel et al., J. Phys. Chem. A 116, 11273 (2012)].
      We compare here, the response of the control field when the reaction path is
      coupled to a second active mode. Constraints on the integrated intensity and on
      the maximum amplitude of the fields are imposed limiting the control landscape.
      Then, optimum field from one-dimensional simulation cannot provide a very high
      yield. Better guess fields based on the two-dimensional model allow the control
      to exploit different mechanisms providing a high control yield. By coupling the
      reaction surface to a bath, we confirm the link between the robustness of the
      field against dissipation and the time spent in the delocalized states above the
      transition barrier. 

PMID- 25591354
TI  - Near edge X-ray absorption mass spectrometry on coronene.
AB  - We have investigated the photoionization and photodissociation of free coronene
      cations C24H12 (+) upon soft X-ray photoabsorption in the carbon K-edge region by
      means of a time-of-flight mass spectrometry approach. Core excitation into an
      unoccupied molecular orbital (below threshold) and core ionization into the
      continuum both leave a C 1s vacancy, that is subsequently filled in an Auger-type
      process. The resulting coronene dications and trications are internally excited
      and cool down predominantly by means of hydrogen emission. Density functional
      theory was employed to determine the dissociation energies for subsequent neutral
      hydrogen loss. A statistical cascade model incorporating these dissociation
      energies agrees well with the experimentally observed dehydrogenation. For double
      ionization, i.e., formation of intermediate C24H12 (3+?)trications, the
      experimental data hint at loss of H(+) ions. This asymmetric fission channel is
      associated with hot intermediates, whereas colder intermediates predominantly
      decay via neutral H loss. 

PMID- 25591355
TI  - Enhanced magnetism of Cu(n) clusters capped with N and endohedrally doped with
      Cr.
AB  - The focus of our work is on the production of highly magnetic materials out of Cu
      clusters. We have studied the relative effects of N-capping as well as N mono
      doping on the structural stability and electronic properties of the small Cu
      clusters using first principles density functional theory based electronic
      structure calculations. We find that the N-capped clusters are more promising in
      producing giant magnetic moments, such as 14 MUB for the Cu6N6 cluster and 29 MUB
      for the icosahedral Cu13N12 cluster. This is accompanied by a substantial
      enhancement in their stability. We suggest that these giant magnetic moments of
      the capped Cun clusters have relevance to the observed room temperature
      ferromagnetism of Cu doped GaN. For cage-like hollow Cu-clusters, an endohedral
      Cr-doping together with the N-capping appears as the most promising means to
      produce stable giant magnetic moments in the copper clusters. 

PMID- 25591356
TI  - Two-color two-photon excited fluorescence of indole: determination of wavelength
      dependent molecular parameters.
AB  - We present a detailed study of two-color two-photon excited fluorescence in
      indole dissolved in propylene glycol. Femtosecond excitation pulses at effective
      wavelengths from 268 to 293.33 nm were used to populate the two lowest indole
      excited states (1)La and (1)Lb and polarized fluorescence was then detected. All
      seven molecular parameters and the two-photon polarization ratio Omega containing
      information on two-photon absorption dynamics, molecular lifetime tauf, and
      rotation correlation time taurot have been determined from experiment and
      analyzed as a function of the excitation wavelength. The analysis of the
      experimental data has shown that (1)Lb-(1)La inversion occurred under the
      conditions of our experiment. The two-photon absorption predominantly populated
      the (1)La state at all excitation wavelengths but in the 287-289 nm area which
      contained an absorption hump of the (1)Lb state 0-0 origin. The components of the
      two-photon excitation tensor S were analyzed giving important information on the
      principal tensor axes and absorption symmetry. The results obtained are in a good
      agreement with the results reported by other groups. The lifetime tauf and the
      rotation correlation time taurot showed no explicit dependence on the effective
      excitation wavelength. Their calculated weighted average values were found to be
      tauf = 3.83 +/- 0.14 ns and taurot = 0.74 +/- 0.06 ns. 

PMID- 25591357
TI  - Atom-diatom scattering dynamics of spinning molecules.
AB  - We present full quantum mechanical scattering calculations using spinning
      molecules as target states for nuclear spin selective atom-diatom scattering of
      reactive D+H2 and F+H2 collisions. Molecules can be forced to rotate uni
      directionally by chiral trains of short, non-resonant laser pulses, with
      different nuclear spin isomers rotating in opposite directions. The calculations
      we present are based on rotational wavepackets that can be created in this
      manner. As our simulations show, target molecules with opposite sense of rotation
      are predominantly scattered in opposite directions, opening routes for spatially
      and quantum state selective scattering of close chemical species. Moreover, two
      dimensional state resolved differential cross sections reveal detailed
      information about the scattering mechanisms, which can be explained to a large
      degree by a classical vector model for scattering with spinning molecules. 

PMID- 25591358
TI  - Van der Waals coefficients beyond the classical shell model.
AB  - Van der Waals (vdW) coefficients can be accurately generated and understood by
      modelling the dynamic multipole polarizability of each interacting object.
      Accurate static polarizabilities are the key to accurate dynamic polarizabilities
      and vdW coefficients. In this work, we present and study in detail a hollow
      sphere model for the dynamic multipole polarizability proposed recently by two of
      the present authors (JT and JPP) to simulate the vdW coefficients for
      inhomogeneous systems that allow for a cavity. The inputs to this model are the
      accurate static multipole polarizabilities and the electron density. A
      simplification of the full hollow-sphere model, the single-frequency
      approximation (SFA), circumvents the need for a detailed electron density and for
      a double numerical integration over space. We find that the hollow-sphere model
      in SFA is not only accurate for nanoclusters and cage molecules (e.g.,
      fullerenes) but also yields vdW coefficients among atoms, fullerenes, and small
      clusters in good agreement with expensive time-dependent density functional
      calculations. However, the classical shell model (CSM), which inputs the static
      dipole polarizabilities and estimates the static higher-order multipole
      polarizabilities therefrom, is accurate for the higher-order vdW coefficients
      only when the interacting objects are large. For the lowest-order vdW coefficient
      C6, SFA and CSM are exactly the same. The higher-order (C8 and C10) terms of the
      vdW expansion can be almost as important as the C6 term in molecular crystals.
      Application to a variety of clusters shows that there is strong non-additivity of
      the long-range vdW interactions between nanoclusters. 

PMID- 25591359
TI  - Probing the early stages of salt nucleation--experimental and theoretical
      investigations of sodium/potassium thiocyanate cluster anions.
AB  - Due to the fast solvent evaporation in electrospray ionization (ESI), the
      concentration of initially dilute electrolyte solutions rapidly increases to
      afford the formation of supersaturated droplets and generation of various
      pristine anhydrous salt clusters in the gas phase. The size, composition, and
      charge distributions of these clusters, in principle, witness the nucleation
      evolution in solutions. Herein, we report a microscopic study on the initial
      stage of nucleation and crystallization of sodium/potassium thiocyanate salt
      solutions simulated in the ESI process. Singly charged Mx(SCN)x+1(-), doubly
      charged My(SCN)y+2(2-) (M = Na, K), and triply charged Kz(SCN)z+3(3-) anion
      clusters (x, y, and z stand for the number of alkali atoms in the singly, doubly,
      and triply charged clusters, respectively) were produced via electrospray of the
      corresponding salt solutions and were characterized by negative ion photoelectron
      spectroscopy (NIPES). The vertical detachment energies (VDEs) of these
      sodium/potassium thiocyanate cluster anions were obtained, and theoretical
      calculations were carried out for the sodium thiocyanate clusters in assisting
      spectral identification. The measured VDEs of singly charged anions Mx(SCN)x+1(-)
      (M = Na and K) demonstrate that they are superhalogen anions. The existence of
      doubly charged anions My(SCN)y+2(2-) (y = 2x, x >= 4 and 3 for M = Na and K,
      respectively) and triply charged anions Kz(SCN)z+3(3-) (z = 3x, x >= 6) was
      initially discovered from the photoelectron spectra for those singly charged
      anions of Mx(SCN)x+1(-) with the same mass-to-charge ratio (m/z), and later
      independently confirmed by the observation of their distinct mass spectral
      distributions and by taking their NIPE spectra for those pure multiply charged
      anions with their m/z different from the singly charged species. For large
      clusters, multiply charged clusters were found to become preferred, but at higher
      temperatures, those multiply charged clusters were suppressed. The series of
      anion clusters investigated here range from molecular-like M1(SCN)2(-) to nano
      sized K22(SCN)25(3-), providing a vivid molecular-level growth pattern reflecting
      the initial salt nucleation process.

PMID- 25591360
TI  - Three-dimensional potential energy surface of Ar-CO.
AB  - A three-dimensional intermolecular potential energy surface of the Ar-CO complex
      has been determined by fitting most of the previously reported spectroscopic
      data, where observed transition frequencies by microwave, millimeter-wave,
      submillimeter-wave, and infrared spectroscopy were reproduced simultaneously
      within their experimental accuracies. A free rotor model Hamiltonian considering
      all the freedom of motions for an atom-diatom system was applied to calculate
      vibration-rotation energies. A three-dimensional potential energy surface
      obtained by ab initio calculations at the CCSD(T)-F12b/aug-cc-pV5Z level of
      theory was parameterized by a model function consisting of 46 parameters. They
      were used as initial values for the least-squares analysis of the experimental
      data. A total of 20 parameters were optimized to reproduce all the spectroscopic
      data. 

PMID- 25591361
TI  - Direct observation of methyl rotor and vib-rotor states of S0 toluene: a revised
      torsional barrier due to torsion-vibration coupling.
AB  - We report a two dimensional, laser induced fluorescence study of the lowest 345
      cm(-1) region of S0 toluene. Methyl rotor levels of 00 up to m = 6 and of 201 up
      to m = 4 are observed. The rotor levels of 00 and 201 have quite different energy
      spacings that are well fit by a model that includes strong torsion-vibration
      coupling between them. The model requires that the rotor barrier height be
      revised from -4.84 cm(-1) (methyl hydrogens in a staggered conformation) to +1.57
      cm(-1) (eclipsed conformation). However, the 3a2" state lies below the 3a1" state
      as expected for a staggered conformation due to energy shifts associated with the
      torsion-vibration coupling. It is shown that the rotor wave-functions exhibit
      little localization at the torsional energy minima. The variation in the m = 0
      wavefunction probability distribution with torsional angle is shown to be very
      similar for the previously accepted negative V6 value and the torsion-vibration
      coupling model as this coupling shifts the phase of the wavefunction by 30
      degrees  compared with its phase for V6 alone. The presence of a strong
      Deltaupsilon = +/- 1 torsion-vibration coupling involving the lowest frequency
      vibrational mode provides a potential pathway for rapid intramolecular
      vibrational energy redistribution at higher energies. 

PMID- 25591362
TI  - The electronic states of TeH(+): a theoretical contribution.
AB  - This work reports the first theoretical characterization of a manifold of
      electronic states of the as yet experimentally unknown monotellurium monohydride
      cation, TeH(+). Both Lambda + S and Omega representations were described showing
      the twelve states correlating with the three lowest (Lambda + S) dissociation
      channels, and the twenty five states associated with the five lowest Omega
      channels. The X (3)Sigma(-) state is split into X1 0(+) and X2 1 separated by
      1049 cm(-1); they are followed by the states a 2 (a (1)Delta) and b 0(+) (b
      (1)Sigma(+)) higher in energy by 8554 and 17 383 cm(-1), respectively. These
      states can accommodate several vibrational energy levels. The potential energy
      curves of the Omega states arising from the bound A (3)Pi, the weakly bound
      (1)Pi, and the repulsive (5)Sigma(-) states have a complex structure as shown by
      the very close avoided crossings just above ~30 000 cm(-1). In particular, a
      double minima potential results for the state A1 2 that in principle could be
      probed experimentally through the A1 2-X2 1 system transitions. The states A2 1,
      b 0(+), and A4 0(+) offer possible routes to experimental investigations
      involving the ground state X1 0(+). Higher energy states are very dense and
      mostly repulsive. The high-level of the electronic structure calculations, by
      providing a global view of the electronic states and reliable spectroscopic
      parameters, is expected to further guide and motivate experimental studies on
      this species. Additional discussions on dipole and transition dipole moments,
      transition probabilities, radiative lifetimes, and a simulation of the single
      ionization spectrum complement the characterization of this system. 

PMID- 25591363
TI  - Accurate spectroscopy of polycyclic aromatic compounds: from the rotational
      spectrum of fluoren-9-one in the millimeter wave region to its infrared spectrum.
AB  - The rotational spectrum of fluoren-9-one, a small oxygenated polycyclic aromatic
      hydrocarbon, has been recorded and assigned in the 52-74.4 GHz region. The
      determined small negative value of the inertia defect (-0.3 u A(2)) has been
      explained in terms of vibrational-rotational coupling constants calculated at the
      B3LYP/cc-pVTZ level of theory. Vibrational anharmonic analysis together with
      second-order vibrational perturbation theory approximation was applied both to
      fluorenone and its reduced form, fluorene, to predict the mid- and near-infrared
      spectra. The data presented here give precise indication on the fluorenone ground
      state structure, allow for an accurate spectral characterization in the
      millimeter wave and infrared regions, and hopefully will facilitate extensive
      radio astronomical searches with large radio telescopes. 

PMID- 25591364
TI  - Effect of Hartree-Fock exact exchange on intramolecular magnetic coupling
      constants of organic diradicals.
AB  - The intramolecular magnetic coupling constant (J) of diradical systems linked
      with five- or six-membered aromatic rings was calculated to obtain the scaling
      factor (experimental J/calculated J ratio) for various density functional theory
      (DFT) functionals. Scaling factors of group A (PBE, TPSSh, B3LYP, B97-1, X3LYP,
      PBE0, and BH&HLYP) and B (M06-L, M06, M06-2X, and M06-HF) were shown to decrease
      as the amount of Hartree-Fock exact exchange (HFx) increases, in other words,
      overestimation of calculated J becomes more severe as the HFx increases. We
      further investigated the effect of HFx fraction of DFT functional on J value,
      spin contamination, and spin density distributions by comparing the B3LYP
      analogues containing different amount of HFx. It was revealed that spin
      contamination and spin densities at each atom increases as the HFx increases.
      Above all, newly developed BLYP-5 functional, which has 5% of HFx, was found to
      have the scaling factor of 1.029, indicating that calculated J values are very
      close to that of experimental values without scaling. BLYP-5 has potential to be
      utilized for accurate evaluation of intramolecular magnetic coupling constant (J)
      of diradicals linked by five- or six-membered aromatic ring couplers. 

PMID- 25591365
TI  - Structural evolution of small ruthenium cluster anions.
AB  - The structures of ruthenium cluster anions have been investigated using a
      combination of trapped ion electron diffraction and density functional theory
      computations in the size range from eight to twenty atoms. In this size range,
      three different structural motifs are found: Ru8(-)-Ru12(-) have simple cubic
      structures, Ru13(-)-Ru16(-) form double layered hexagonal structures, and larger
      clusters form close packed motifs. For Ru17(-), we find hexagonal close packed
      stacking, whereas octahedral structures occur for Ru18(-)-Ru20(-). Our
      calculations also predict simple cubic structures for the smaller clusters Ru4(-)
      Ru7(-), which were not accessible to electron diffraction measurements.

PMID- 25591366
TI  - Multi-scale modelling of uranyl chloride solutions.
AB  - Classical molecular dynamics simulations with explicit polarization have been
      successfully used to determine the structural and thermodynamic properties of
      binary aqueous solutions of uranyl chloride (UO2Cl2). Concentrated aqueous
      solutions of uranyl chloride have been studied to determine the hydration
      properties and the ion-ion interactions. The bond distances and the coordination
      number of the hydrated uranyl are in good agreement with available experimental
      data. Two stable positions of chloride in the second hydration shell of uranyl
      have been identified. The UO2(2+)-Cl(-) association constants have also been
      calculated using a multi-scale approach. First, the ion-ion potential averaged
      over the solvent configurations at infinite dilution (McMillan-Mayer potential)
      was calculated to establish the dissociation/association processes of UO2 (2+)
      Cl(-) ion pairs in aqueous solution. Then, the association constant was
      calculated from this potential. The value we obtained for the association
      constant is in good agreement with the experimental result (KUO2Cl(+) = 1.48 l
      mol(-1)), but the resulting activity coefficient appears to be too low at molar
      concentration.

PMID- 25591367
TI  - Water density fluctuations relevant to hydrophobic hydration are unaltered by
      attractions.
AB  - An understanding of density fluctuations in bulk water has made significant
      contributions to our understanding of the hydration and interactions of
      idealized, purely repulsive hydrophobic solutes. To similarly inform the
      hydration of realistic hydrophobic solutes that have dispersive interactions with
      water, here we characterize water density fluctuations in the presence of
      attractive fields that correspond to solute-water attractions. We find that when
      the attractive field acts only in the solute hydration shell, but not in the
      solute core, it does not significantly alter water density fluctuations in the
      solute core region. We further find that for a wide range of solute sizes and
      attraction strengths, the free energetics of turning on the attractive fields in
      bulk water are accurately captured by linear response theory. Our results also
      suggest strategies for more efficiently estimating hydration free energies of
      realistic solutes in bulk water and at interfaces. 

PMID- 25591368
TI  - Effect of the computational domain size and shape on the self-diffusion
      coefficient in a Lennard-Jones liquid.
AB  - In the present study, molecular dynamics (MD) simulations on the monatomic
      Lennard-Jones liquid in a periodic boundary system were performed in order to
      elucidate the effect of the computational domain size and shape on the self
      diffusion coefficient measured by the system. So far, the system size dependence
      in cubic computational domains has been intensively investigated and these
      studies showed that the diffusion coefficient depends linearly on the inverse of
      the system size, which is theoretically predicted based on the hydrodynamic
      interaction. We examined the system size effect not only in the cubic cell
      systems but also in rectangular cell systems which were created by changing one
      side length of the cubic cell with the system density kept constant. As a result,
      the diffusion coefficient in the direction perpendicular to the long side of the
      rectangular cell significantly increases more or less linearly with the side
      length. On the other hand, the diffusion coefficient in the direction along the
      long side is almost constant or slightly decreases. Consequently, anisotropy of
      the diffusion coefficient emerges in a rectangular cell with periodic boundary
      conditions even in a bulk liquid simulation. This unexpected result is of
      critical importance because rectangular fluid systems confined in nanospace,
      which are present in realistic nanoscale technologies, have been widely studied
      in recent MD simulations. In order to elucidate the underlying mechanism for this
      serious system shape effect on the diffusion property, the correlation structures
      of particle velocities were examined. 

PMID- 25591369
TI  - A first principles approach to the electronic properties of liquid and
      supercritical CO2.
AB  - The electronic absorption spectra of liquid and supercritical CO2 (scCO2) are
      investigated by coupling a many-body energy decomposition scheme to
      configurations generated by Born-Oppenheimer molecular dynamics. A Frenkel
      exciton Hamiltonian formalism was adopted and the excitation energies were
      calculated with time dependent density functional theory. A red-shift of ~ 0.2 eV
      relative to the gas-phase monomer is observed for the first electronic absorption
      maximum in liquid and scCO2. The origin of this shift, which is not very
      dependent on deviations from the linearity of the CO2 molecule, is mainly related
      to polarization effects. However, the geometry changes of the CO2 monomer induced
      by thermal effects and intermolecular interactions in condensed phase lead to the
      appearance of an average monomeric electric dipole moment<MU>= 0.26 +/- 0.04 D
      that is practically the same at liquid and supercritical conditions. The
      predicted average quadrupole moment for both liquid and scCO2 is<Theta>= - 5.5 D
      A, which is increased by ~ -0.9 D A relative to its gas-phase value. The
      importance of investigating the electronic properties for a better understanding
      of the role played by CO2 in supercritical solvation is stressed.

PMID- 25591370
TI  - Flexible confinement leads to multiple relaxation regimes in glassy colloidal
      liquids.
AB  - Understanding relaxation of supercooled fluids is a major challenge and confining
      such systems can lead to bewildering behaviour. Here, we exploit an optically
      confined colloidal model system in which we use reduced pressure as a control
      parameter. The dynamics of the system are "Arrhenius" at low and moderate
      pressure, but at higher pressures relaxation is faster than expected. We
      associate this faster relaxation with a decrease in density adjacent to the
      confining boundary due to local ordering in the system enabled by the flexible
      wall. 

PMID- 25591371
TI  - On the influence of polarization effects in predicting the interfacial structure
      and capacitance of graphene-like electrodes in ionic liquids.
AB  - The electric double layer (CD) and electrode quantum (CQ) capacitances of
      graphene-based supercapacitors are investigated using a combined molecular
      dynamics and density functional theory approach. In particular, we compare an
      approach that includes electronic polarization to one that is polarization-free
      by evaluating both CD and CQ using [EMIM][BF4] ionic liquid as a model
      electrolyte. Our results indicate that the inclusion of polarization effects can
      yield higher CD values-in this study by up to 40% around +/-2 V-which we
      attribute primarily to the presence of charge smearing at the electrode
      electrolyte interface. On the other hand, we find that the polarization-induced
      distortion of the electronic structure of graphene does not noticeably alter the
      predicted CQ. Our analysis suggests that an accurate description of the spatial
      charge distribution at the graphene interface due to polarization is necessary to
      improve our predictive capabilities, though more notably for CD. However, the
      conventional polarization-free approximation can serve as an efficient tool to
      study trends associated with both the CQ and CD at the interface of various
      graphene-like materials. 

PMID- 25591372
TI  - Structure and dynamics of H2O vis-a-vis phenylalanine recognition at a DPPC lipid
      membrane via interfacial H-bond types: insights from polarized FT-IRRAS and ADMP
      simulations.
AB  - Preferential and enantioselective interactions of L-/D-Phenylalanine (L-Phe and D
      Phe) and butoxycarbonyl-protected L-/D-Phenylalanine (LPA and DPA) as guest with
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine (L-DPPC) as host were tapped by using
      real time Fourier transform infrared reflection absorption spectroscopy (FT
      IRRAS). Polarization-modulated FT-IRRAS of DPPC monolayers above the
      phenylalanine modified subphases depicted fine structure/conformation differences
      under considerations of controlled 2D surface pressure. Selective molecular
      recognition of D-enantiomer over L-enantiomer driven by the DPPC head group via H
      bonding and electrostatic interactions was evident spectroscopically.
      Accordingly, binding constants (K) of 145, 346, 28, and 56 M(-1) for LPA, DPA, L
      Phe, and D-Phe, respectively, were estimated. The real time FT-IRRAS water bands
      were strictly conformation sensitive. The effect of micro-solvation on the
      structure and stability of the 1:1 diastereomeric L-lipid?, LPA/DPA and L-lipid?,
      (L/D)-Phe adducts was investigated with the aid of Atom-centered Density Matrix
      Propagation (ADMP), a first principle quantum mechanical molecular dynamics
      approach. The phosphodiester fragment was the primary site of hydration where
      specific solvent interactions were simulated through single- and triple- "water
      phosphate" interactions, as water cluster's "tetrahedral dice" to a "trimeric
      motif" transformation as a partial de-clusterization was evident. Under all the
      hydration patterns considered in both static and dynamic descriptions of density
      functional theory, L-lipid/D-amino acid enantiomer adducts continued to be stable
      structures while in dynamic systems, water rearranged without getting "squeezed
      out" in the process of recognition. In spite of the challenging computational
      realm of this multiscale problem, the ADMP simulated molecular interactions
      complying with polarized vibrational spectroscopy unraveled a novel route to
      chiral recognition and interfacial water structure.

PMID- 25591373
TI  - Experimental evidence for an optical interference model for vibrational sum
      frequency generation on multilayer organic thin film systems. I. Electric dipole
      approximation.
AB  - In the field of vibrational sum frequency generation spectroscopy (VSFG) applied
      to organic thin film systems, a significant challenge to data analysis is in the
      accurate description of optical interference effects. Herein, we provide
      experimental evidence that a model recently developed in our lab provides an
      accurate description of this phenomenon. We studied the organic small molecule
      N,N'-dioctyl-3,4,9,10-perylenedicarboximide vapor deposited as a thickness
      gradient on silicon wafer substrates with two oxide thicknesses and two surface
      preps. VSFG data were obtained using the ssp and the sps polarization
      combinations in the imide carbonyl stretching region as a function of organic
      thickness. In this first of two reports, the data are modeled and interpreted
      within the ubiquitous electric dipole approximation for VSFG. The intrinsic
      sample responses are parameterized during the fitting routines while optical
      interference effects are simply calculated from the model using known refractive
      indices, thin film thicknesses, and beam angles. The results indicate that the
      thin film model provides a good description of optical interferences, indicating
      that interfacial terms are significant. Inconsistencies between the fitting
      results within the bounds of the electric dipole response motivate deliberation
      for additional effects to be considered in the second report. 

PMID- 25591374
TI  - Experimental evidence for an optical interference model for vibrational sum
      frequency generation on multilayer organic thin film systems. II. Consideration
      for higher order terms.
AB  - The generalized optical interference model for interfacial contributions to
      vibrational sum frequency generation (VSFG) spectroscopic signals from organic
      thin film systems is extended to include a description of optical interferences
      contained in the thin film bulk response. This is based on electric quadrupolar
      interactions with the input fields and includes a discussion on possible
      contribution from the electric quadrupolar polarization. VSFG data from the first
      of this two part report are analyzed and include effects from higher order
      responses, for both bulk and higher order interfacial terms. The results indicate
      that although it is capable of capturing many of the data features, the electric
      dipole treatment is likely not a complete description of the VSFG intensity data
      from this system. An analysis based on the signs of the resulting response
      amplitudes is used to deduce the relative magnitude of the electric dipole and
      higher order interfacial terms. It is found that the buried interface is closer
      to satisfying the electric dipole approximation, consistent with smaller field
      gradients due to closer index matching between the organic thin film and
      substrate relative to air. The procedure outlined in this work allows for the
      difficult task of deducing a physical picture of average molecular orientation at
      the buried interface of a multilayer organic thin film system while including
      higher order effects. 

PMID- 25591375
TI  - Orbital line-up at poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (MEH
      PPV)/poly(3-hexylthiophene) (P3HT) heterojunction.
AB  - The poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV)/poly(3
      hexylthiophene) (P3HT) heterojunction was investigated by photoemission
      spectroscopy. The orbital line-up at the MEH-PPV/P3HT heterojunction was
      determined based on the data of X-ray and ultra-violet photoemission
      measurements. The results were discussed with reference to the Induced Density of
      Interface States (IDIS) and integer charge transfer models. The predicted
      interface orbital line-up by IDIS is in agreement with measured energy alignment
      of the investigated interface. This suggests the IDIS model is also valid for
      polymer/polymer heterojunctions. 

PMID- 25591376
TI  - Half-metallic properties, single-spin negative differential resistance, and large
      single-spin Seebeck effects induced by chemical doping in zigzag-edged graphene
      nanoribbons.
AB  - Ab initio calculations combining density-functional theory and nonequilibrium
      Green's function are performed to investigate the effects of either single B atom
      or single N atom dopant in zigzag-edged graphene nanoribbons (ZGNRs) with the
      ferromagnetic state on the spin-dependent transport properties and thermospin
      performances. A spin-up (spin-down) localized state near the Fermi level can be
      induced by these dopants, resulting in a half-metallic property with 100%
      negative (positive) spin polarization at the Fermi level due to the destructive
      quantum interference effects. In addition, the highly spin-polarized electric
      current in the low bias-voltage regime and single-spin negative differential
      resistance in the high bias-voltage regime are also observed in these doped
      ZGNRs. Moreover, the large spin-up (spin-down) Seebeck coefficient and the very
      weak spin-down (spin-up) Seebeck effect of the B(N)-doped ZGNRs near the Fermi
      level are simultaneously achieved, indicating that the spin Seebeck effect is
      comparable to the corresponding charge Seebeck effect. 

PMID- 25591377
TI  - Time-resolved X-ray diffraction and Raman studies of the phase transition
      mechanisms of methane hydrate.
AB  - The mechanisms by which methane hydrate transforms from an sI to sH structure and
      from an sH to filled-ice Ih structure were examined using time-resolved X-ray
      diffractometry (XRD) and Raman spectroscopy in conjunction with charge-coupled
      device camera observation under fixed pressure conditions. The XRD data obtained
      for the sI-sH transition at 0.8 GPa revealed an inverse correlation between sI
      and sH, suggesting that the sI structure is replaced by sH. Meanwhile, the Raman
      analysis demonstrated that although the 12-hedra of sI are retained, the 14-hedra
      are replaced sequentially by additional 12-hedra, modified 12-hedra, and 20-hedra
      cages of sH. With the sH to filled-ice Ih transition at 1.8 GPa, both the XRD and
      Raman data showed that this occurs through a sudden collapse of the sH structure
      and subsequent release of solid and fluid methane that is gradually incorporated
      into the filled-ice Ih to complete its structure. This therefore represents a
      typical reconstructive transition mechanism. 

PMID- 25591378
TI  - The nature of interfaces and charge trapping sites in photocatalytic mixed-phase
      TiO2 from first principles modeling.
AB  - Mixed phase rutile/anatase catalysts show increased reactivity compared with the
      pure phases alone. However, the mechanism causing this effect is not fully
      understood. The electronic properties of the interface and the relative energy of
      the electron in each phase play a key role in lowering the rate of recombination
      of electron hole pairs. Using density functional theory and the +U correction, we
      calculated the bands offsets between the phases taking into account the effect of
      the interface. Our model included several thousands atoms, and thus is a good
      representation of an interface between actual nanoparticles. We found rutile to
      have both higher conduction and valence band offsets than rutile, leading to an
      accumulation of electrons in the anatase phase accompanied by hole accumulation
      in the rutile phase. We also probed the electronic structure of our
      heterostructure and found a gap state caused by electrons localized in
      undercoordinated Ti atoms which were present within the interfacial region.
      Interfaces between bulk materials and between exposed surfaces both showed
      electron trapping at undercoordinated sites. These undercoordinated (typically
      four) atoms present localized electrons that could enable reduction reactions in
      the interfacial region, and could explain the increased reactivity of mixed-phase
      TiO2 photocatalyst materials. 

PMID- 25591379
TI  - Critical island-size, stability, and morphology of 2D colloidal Au nanoparticle
      islands.
AB  - The critical island-size, stability, and morphology of 2D colloidal Au
      nanoparticle islands formed during drop-drying are studied using an empirical
      potential which takes into account core-core, ligand-ligand, and ligand-solvent
      interactions. Good agreement with experiment is obtained for the dependence of
      the critical island-size on nanoparticle diameter. Our results for the critical
      length-scale for smoothing via edge-diffusion are also consistent with the
      limited facet size and island-relaxation observed in experiments. In addition,
      the relatively high rate of monomer diffusion on an island as well as the low
      barrier for interlayer diffusion are consistent with experimental observations
      that second-layer growth does not occur until after the first layer is complete. 

PMID- 25591381
TI  - The shapes of simple three and four junction comb polymers.
AB  - A scheme originally proposed by G. Wei [Physica A 222, 152 (1995); Physica A 222,
      155 (1995)] is redesigned to produce numerical shape parameters of arbitrary tree
      branched polymers based on the Kirchhoff matrix eigenvalue spectrum. This method
      and two different Monte Carlo techniques (pivot and growth) are employed to
      investigate the asphericity of three and four junction comb polymers in both the
      ideal and excluded volume regimes. It is found that the extrapolated g-ratio and
      asphericity values obtained by all of these methods are in excellent agreement
      with each other and the available theory in the ideal regime and that polymers
      with a complete set of interior branches display a more sphere-like shape. 

PMID- 25591380
TI  - Novel phases of lithium-aluminum binaries from first-principles structural
      search.
AB  - Intermetallic Li-Al compounds are on the one hand key materials for light-weight
      engineering, and on the other hand, they have been proposed for high-capacity
      electrodes for Li batteries. We determine from first-principles the phase diagram
      of Li-Al binary crystals using the minima hopping structural prediction method.
      Beside reproducing the experimentally reported phases (LiAl, Li3Al2, Li9Al4,
      LiAl3, and Li2Al), we unveil a structural variety larger than expected by
      discovering six unreported binary phases likely to be thermodynamically stable.
      Finally, we discuss the behavior of the elastic constants and of the electric
      potential profile of all Li-Al stable compounds as a function of their
      stoichiometry. 

PMID- 25591382
TI  - Structural transitions and long-time self-diffusion of interacting colloids
      confined by a parabolic potential.
AB  - We report on the ordering and dynamics of interacting colloidal particles
      confined by a parabolic potential. By means of Brownian dynamics simulations, we
      find that by varying the magnitude of the trap stiffness, it is possible to
      control the dimension of the system and, thus, explore both the structural
      transitions and the long-time self-diffusion coefficient as a function of the
      degree of confinement. We particularly study the structural ordering in the
      directions perpendicular and parallel to the confinement. Further analysis of the
      local distribution of the first-neighbors layer allows us to identify the
      different structural phases induced by the parabolic potential. These results are
      summarized in a structural state diagram that describes the way in which the
      colloidal suspension undergoes a structural re-ordering while increasing the
      confinement. To fully understand the particle dynamics, we take into account
      hydrodynamic interactions between colloids; the parabolic potential constricts
      the available space for the colloids, but it does not act on the solvent. Our
      findings show a non-linear behavior of the long-time self-diffusion coefficient
      that is associated to the structural transitions induced by the external field. 

PMID- 25591383
TI  - AIREBO-M: a reactive model for hydrocarbons at extreme pressures.
AB  - The Adaptive Intermolecular Reactive Empirical Bond Order potential (AIREBO) for
      hydrocarbons has been widely used to study dynamic bonding processes under
      ambient conditions. However, its intermolecular interactions are modeled by a
      Lennard-Jones (LJ) potential whose unphysically divergent power-law repulsion
      causes AIREBO to fail when applied to systems at high pressure. We present a
      modified potential, AIREBO-M, where we have replaced the singular Lennard-Jones
      potential with a Morse potential. We optimize the new functional form to improve
      intermolecular steric repulsions, while preserving the ambient thermodynamics of
      the original potentials as much as possible. The potential is fit to experimental
      measurements of the layer spacing of graphite up to 14 GPa and first principles
      calculations of steric interactions between small alkanes. To validate AIREBO-M's
      accuracy and transferability, we apply it to a graphite bilayer and orthorhombic
      polyethylene. AIREBO-M gives bilayer compression consistent with quantum
      calculations, and it accurately reproduces the quasistatic and shock compression
      of orthorhombic polyethlyene up to at least 40 GPa. 

PMID- 25591384
TI  - A model-free temperature-dependent conformational study of n-pentane in nematic
      liquid crystals.
AB  - The proton NMR spectra of n-pentane orientationally ordered in two nematic liquid
      crystal solvents are studied over a wide temperature range and analysed using
      covariance matrix adaptation evolutionary strategy. Since alkanes possess small
      electrostatic moments, their anisotropic intermolecular interactions are
      dominated by short-range size-and-shape effects. As we assumed for n-butane, the
      anisotropic energy parameters of each n-pentane conformer are taken to be
      proportional to those of ethane and propane, independent of temperature. The
      observed temperature dependence of the n-pentane dipolar couplings allows a model
      free separation between conformer degrees of order and conformer probabilities,
      which cannot be achieved at a single temperature. In this way for n-pentane 13
      anisotropic energy parameters (two for trans trans, tt, five for trans gauche,
      tg, and three for each of gauche+ gauche+, pp, and gauche+ gauche-, pm), the
      isotropic trans-gauche energy difference Etg and its temperature coefficient
      Etg(') are obtained. The value obtained for the extra energy associated with the
      proximity of the two methyl groups in the gauche+ gauche- conformers (the pentane
      effect) is sensitive to minute details of other assumptions and is thus fixed in
      the calculations. Conformer populations are affected by the environment. In
      particular, anisotropic interactions increase the trans probability in the
      ordered phase.

PMID- 25591385
TI  - Investigation of the nanoviscosity effect of a G-quadruplex and single-strand DNA
      using fluorescence correlation spectroscopy.
AB  - Guanine (G)-quadruplexes are of interest because of their presence in the
      telomere sequence and the oncogene promoter region. Their diffusion and change of
      structure, especially in high viscosity solutions, are important for
      understanding their dynamics. G-quadruplexes may have less effective viscosity
      (nanoviscosity) when they are smaller than the solvent molecules. In this paper,
      we report the difference in the diffusion dynamics of the G-rich DNA sequences of
      single-strand DNA (ssDNA) and the G-quadruplex in aqueous, sucrose, and
      polyethylene glycol (PEG) solutions. From experiments with aqueous and sucrose
      solutions, we confirm that a simple diffusion model according to the viscosity is
      appropriate. In the PEG experiments, the nanoviscosity effect is observed
      according to PEG's molecular weight. In the PEG 200 solution, both the ssDNA and
      the G-quadruplex possess macroviscosity. In the PEG 10,000 solution, the G
      quadruplex possesses nanoviscosity and the ssDNA possesses macroviscosity,
      whereas, in the PEG 35,000 solution, both ssDNA and the G-quadruplex possess
      nanoviscosity. The experimental results are consistent with the theoretical
      predictions.

PMID- 25591386
TI  - Dissipation enhanced vibrational sensing in an olfactory molecular switch.
AB  - Motivated by a proposed olfactory mechanism based on a vibrationally activated
      molecular switch, we study electron transport within a donor-acceptor pair that
      is coupled to a vibrational mode and embedded in a surrounding environment. We
      derive a polaron master equation with which we study the dynamics of both the
      electronic and vibrational degrees of freedom beyond previously employed
      semiclassical (Marcus-Jortner) rate analyses. We show (i) that in the absence of
      explicit dissipation of the vibrational mode, the semiclassical approach is
      generally unable to capture the dynamics predicted by our master equation due to
      both its assumption of one-way (exponential) electron transfer from donor to
      acceptor and its neglect of the spectral details of the environment; (ii) that by
      additionally allowing strong dissipation to act on the odorant vibrational mode,
      we can recover exponential electron transfer, though typically at a rate that
      differs from that given by the Marcus-Jortner expression; (iii) that the ability
      of the molecular switch to discriminate between the presence and absence of the
      odorant, and its sensitivity to the odorant vibrational frequency, is enhanced
      significantly in this strong dissipation regime, when compared to the case
      without mode dissipation; and (iv) that details of the environment absent from
      previous Marcus-Jortner analyses can also dramatically alter the sensitivity of
      the molecular switch, in particular, allowing its frequency resolution to be
      improved. Our results thus demonstrate the constructive role dissipation can play
      in facilitating sensitive and selective operation in molecular switch devices, as
      well as the inadequacy of semiclassical rate equations in analysing such
      behaviour over a wide range of parameters. 

PMID- 25591387
TI  - A comparative analysis of clustering algorithms: O2 migration in truncated
      hemoglobin I from transition networks.
AB  - The ligand migration network for O2-diffusion in truncated Hemoglobin N is
      analyzed based on three different clustering schemes. For coordinate-based
      clustering, the conventional k-means and the kinetics-based Markov Clustering
      (MCL) methods are employed, whereas the locally scaled diffusion map (LSDMap)
      method is a collective-variable-based approach. It is found that all three
      methods agree well in their geometrical definition of the most important docking
      site, and all experimentally known docking sites are recovered by all three
      methods. Also, for most of the states, their population coincides quite
      favourably, whereas the kinetics of and between the states differs. One of the
      major differences between k-means and MCL clustering on the one hand and LSDMap
      on the other is that the latter finds one large primary cluster containing the
      Xe1a, IS1, and ENT states. This is related to the fact that the motion within the
      state occurs on similar time scales, whereas structurally the state is found to
      be quite diverse. In agreement with previous explicit atomistic simulations, the
      Xe3 pocket is found to be a highly dynamical site which points to its potential
      role as a hub in the network. This is also highlighted in the fact that LSDMap
      cannot identify this state. First passage time distributions from MCL clusterings
      using a one- (ligand-position) and two-dimensional (ligand-position and protein
      structure) descriptor suggest that ligand- and protein-motions are coupled. The
      benefits and drawbacks of the three methods are discussed in a comparative
      fashion and highlight that depending on the questions at hand the best-performing
      method for a particular data set may differ. 

PMID- 25591388
TI  - Comment on "Steady-state fluctuations of a genetic feedback loop: an exact
      solution" [J. Chem. Phys. 137, 035104 (2012)].

PMID- 25591389
TI  - Response surface methodology to optimize partition and purification of two
      recombinant oxidoreductase enzymes, glucose dehydrogenase and d-galactose
      dehydrogenase in aqueous two-phase systems.
AB  - Oxidoreductases are an important family of enzymes that are used in many
      biotechnological processes. An experimental design was applied to optimize
      partition and purification of two recombinant oxidoreductases, glucose
      dehydrogenase (GDH) from Bacillus subtilis and d-galactose dehydrogenase (GalDH)
      from Pseudomonas fluorescens AK92 in aqueous two-phase systems (ATPS). Response
      surface methodology (RSM) with a central composite rotatable design (CCRD) was
      performed to optimize critical factors like polyethylene glycol (PEG)
      concentration, concentration of salt and pH value. The best partitioning
      conditions was achieved in an ATPS composed of 12% PEG-6000, 15% K2HPO4 with pH
      7.5 at 25 degrees C, which ensured partition coefficient (KE) of 66.6 and 45.7
      for GDH and GalDH, respectively. Under these experimental conditions, the
      activity of GDH and GalDH was 569.5U/ml and 673.7U/ml, respectively. It was found
      that these enzymes preferentially partitioned into the top PEG-rich phase and
      appeared as single bands on SDS-PAGE gel. Meanwhile the validity of the response
      model was confirmed by a good agreement between predicted and experimental
      results. Collectively, according to the obtained data it can be inferred that the
      ATPS optimization using RSM approach can be applied for recovery and purification
      of any enzyme from oxidoreductase family. 

PMID- 25591390
TI  - Ebola outbreaks in 2014.

PMID- 25591391
TI  - Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low
      birthweight in Papua New Guinea: a randomised controlled trial.
AB  - BACKGROUND: Intermittent preventive treatment in pregnancy has not been evaluated
      outside of Africa. Low birthweight (LBW, <2,500 g) is common in Papua New Guinea
      (PNG) and contributing factors include malaria and reproductive tract infections.
      METHODS: From November 2009 to February 2013, we conducted a parallel group,
      randomised controlled trial in pregnant women (<= 26 gestational weeks) in PNG.
      Sulphadoxine-pyrimethamine (1,500/75 mg) plus azithromycin (1 g twice daily for 2
      days) (SPAZ) monthly from second trimester (intervention) was compared against
      sulphadoxine-pyrimethamine and chloroquine (450 to 600 mg, daily for three days)
      (SPCQ) given once, followed by SPCQ placebo (control). Women were assigned to
      treatment (1:1) using a randomisation sequence with block sizes of 32.
      Participants were blinded to assignments. The primary outcome was LBW. Analysis
      was by intention-to-treat. RESULTS: Of 2,793 women randomised, 2,021 (72.4%) were
      included in the primary outcome analysis (SPCQ: 1,008; SPAZ: 1,013). The
      prevalence of LBW was 15.1% (305/2,021). SPAZ reduced LBW (risk ratio [RR]: 0.74,
      95% CI: 0.60-0.91, P = 0.005; absolute risk reduction (ARR): 4.5%, 95% CI: 1.4
      7.6; number needed to treat: 22), and preterm delivery (0.62, 95% CI: 0.43-0.89,
      P = 0.010), and increased mean birthweight (41.9 g, 95% CI: 0.2-83.6, P = 0.049).
      SPAZ reduced maternal parasitaemia (RR: 0.57, 95% CI: 0.35-0.95, P = 0.029) and
      active placental malaria (0.68, 95% CI: 0.47-0.98, P = 0.037), and reduced
      carriage of gonorrhoea (0.66, 95% CI: 0.44-0.99, P = 0.041) at second visit.
      There were no treatment-related serious adverse events (SAEs), and the number of
      SAEs (intervention 13.1% [181/1,378], control 12.7% [174/1,374], P = 0.712) and
      AEs (intervention 10.5% [144/1,378], control 10.8% [149/1,374], P = 0.737) was
      similar. A major limitation of the study was the high loss to follow-up for
      birthweight. CONCLUSIONS: SPAZ was efficacious and safe in reducing LBW, possibly
      acting through multiple mechanisms including the effect on malaria and on
      sexually transmitted infections. The efficacy of SPAZ in the presence of
      resistant parasites and the contribution of AZ to bacterial antibiotic resistance
      require further study. The ability of SPAZ to improve pregnancy outcomes warrants
      further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 (06 April
      2010).

PMID- 25591392
TI  - Somatic chromosomal translocation between Ewsr1 and Fli1 loci leads to dilated
      cardiomyopathy in a mouse model.
AB  - A mouse model that recapitulates the human Ewing's sarcoma-specific chromosomal
      translocation was generated utilizing the Cre/loxP-mediated recombination
      technique. A cross between Ewsr1-loxP and Fli1-loxP mice and expression of
      ubiquitous Cre recombinase induced a specific translocation between Ewsr1 and
      Fli1 loci in systemic organs of both adult mice and embryos. As a result Ewsr1
      Fli1 fusion transcripts were expressed, suggesting a functional Ews-Fli1 protein
      might be synthesized in vivo. However, by two years of age, none of the Ewsr1
      loxP/Fli1-loxP/CAG-Cre (EFCC) mice developed any malignancies, including Ewing
      like small round cell sarcoma. Unexpectedly, all the EFCC mice suffered from
      dilated cardiomyopathy and died of chronic cardiac failure. Genetic recombination
      between Ewsr1 and Fli1 was confirmed in the myocardial tissue and apoptotic cell
      death of cardiac myocytes was observed at significantly higher frequency in EFCC
      mice. Moreover, expression of Ews-Fli1 in the cultured cardiac myocytes induced
      apoptosis. Collectively, these results indicated that ectopic expression of the
      Ews-Fli1 oncogene stimulated apoptotic signals, and suggested an important
      relationship between oncogenic signals and cellular context in the cell-of-origin
      of Ewing's sarcoma. 

PMID- 25591393
TI  - Effectiveness of maritime safety control in different navigation zones using a
      spatial sequential DEA model: Yangtze River case.
AB  - This paper aims to analyze the effectiveness of maritime safety control from the
      perspective of safety level along the Yangtze River with special considerations
      for navigational environments. The influencing variables of maritime safety are
      reviewed, including ship condition, maritime regulatory system, human reliability
      and navigational environment. Because the former three variables are generally
      assumed to be of the same level of safety, this paper focuses on studying the
      impact of navigational environments on the level of safety in different
      waterways. An improved data envelopment analysis (DEA) model is proposed by
      treating the navigational environment factors as inputs and ship accident data as
      outputs. Moreover, because the traditional DEA model cannot provide an overall
      ranking of different decision making units (DMUs), the spatial sequential
      frontiers and grey relational analysis are incorporated into the DEA model to
      facilitate a refined assessment. Based on the empirical study results, the
      proposed model is able to solve the problem of information missing in the prior
      models and evaluate the level of safety with a better accuracy. The results of
      the proposed DEA model are further compared with an evidential reasoning (ER)
      method, which has been widely used for level of safety evaluations. A sensitivity
      analysis is also conducted to better understand the relationship between the
      variation of navigational environments and level of safety. The sensitivity
      analysis shows that the level of safety varies in terms of traffic flow. It
      indicates that appropriate traffic control measures should be adopted for
      different waterways to improve their safety. This paper presents a practical
      method of conducting maritime level of safety assessments under dynamic
      navigational environment. 

PMID- 25591395
TI  - Caffeine induces high expression of cyp-35A family genes and inhibits the early
      larval development in Caenorhabditis elegans.
AB  - Intake of caffeine during pregnancy can cause retardation of fetal development.
      Although the significant influence of caffeine on animal development is widely
      recognized, much remains unknown about its mode of action because of its
      pleiotropic effects on living organisms. In the present study, by using
      Caenorhabditis elegans as a model organism, the effects of caffeine on
      development were examined. Brood size, embryonic lethality, and percent larval
      development were investigated, and caffeine was found to inhibit the development
      of C. elegans at most of the stages in a dosage-dependent fashion. Upon treatment
      with 30 mM caffeine, the majority (86.1 +/- 3.4%) of the L1 larvae were
      irreversibly arrested without further development. In contrast, many of the late
      stage larvae survived and grew to adults when exposed to the same 30 mM caffeine.
      These results suggest that early-stage larvae are more susceptible to caffeine
      than later-stage larvae. To understand the metabolic responses to caffeine
      treatment, the levels of expression of cytochrome P450 (cyp) genes were examined
      with or without caffeine treatment using comparative micro-array, and it was
      found that the expression of 24 cyp genes was increased by more than 2-fold (p <
      0.05). Among them, induction of the cyp-35A gene family was the most prominent.
      Interestingly, depletion of the cyp-35A family genes one-by-one or in combination
      through RNA interference resulted in partial rescue from early larval
      developmental arrest caused by caffeine treatment, suggesting that the high-level
      induction of cyp-35A family genes can be fatal to the development of early-stage
      larvae. 

PMID- 25591399
TI  - QSAR analysis for nano-sized layered manganese-calcium oxide in water oxidation:
      An application of chemometric methods in artificial photosynthesis.
AB  - Water oxidation is among the most important reactions in artificial
      photosynthesis, and nano-sized layered manganese-calcium oxides are efficient
      catalysts toward this reaction. Herein, a quantitative structure-activity
      relationship (QSAR) model was constructed to predict the catalytic activities of
      twenty manganese-calcium oxides toward water oxidation using multiple linear
      regression (MLR) and genetic algorithm (GA) for multivariate calibration and
      feature selection, respectively. Although there are eight controlled parameters
      during synthesizing of the desired catalysts including ripening time,
      temperature, manganese content, calcium content, potassium content, the ratio of
      calcium:manganese, the average manganese oxidation state and the surface of
      catalyst, by using GA only three of them (potassium content, the ratio of
      calcium:manganese and the average manganese oxidation state) were selected as the
      most effective parameters on catalytic activities of these compounds. The model's
      accuracy criteria such as R(2)test and Q(2)test in order to predict catalytic
      rate for external test set experiments; were equal to 0.941 and 0.906,
      respectively. Therefore, model reveals acceptable capability to anticipate the
      catalytic activity. 

PMID- 25591398
TI  - Screening and characterization of a novel RNA aptamer that specifically binds to
      human prostatic acid phosphatase and human prostate cancer cells.
AB  - Prostatic acid phosphatase (PAP) expression increases proportionally with
      prostate cancer progression, making it useful in prognosticating intermediate to
      high-risk prostate cancers. A novel ligand that can specifically bind to PAP
      would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to
      target molecules with high specificity and have key advantages such as low
      immunogenicity and easy synthesis. Here, human PAP-specific aptamers were
      screened from a 2'-fluoropyrimidine (FY)-modified RNA library by SELEX. The
      candidate aptamer families were identified within six rounds followed by analysis
      of their sequences and PAP-specific binding. A gel shift assay was used to
      identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a
      Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the
      6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90
      negative control cells did not bind the 6N aptamer. Systematic minimization
      analyses revealed that 50 nucleotide sequences and their two hairpin structures
      in the 6N 2'-FY RNA aptamer were equally important for PAP binding. Renewed
      interest in PAP combined with the versatility of RNA aptamers, including
      conjugation of anti-cancer drugs and nano-imaging probes, could open up a new
      route for early theragnosis of prostate cancer. 

PMID- 25591400
TI  - Flow rate dependent extra-column variance from injection in capillary liquid
      chromatography.
AB  - Efficiency and resolution in capillary liquid chromatography (LC) can be
      significantly affected by extra-column band broadening, especially for isocratic
      separations. This is particularly a concern in evaluating column bed structure
      using non-retained test compounds. The band broadening due to an injector
      supplied with a commercially available capillary LC system was characterized from
      experimental measurements. The extra-column variance from the injection valve was
      found to have an extra-column contribution independent of the injection volume,
      showing an exponential dependence on flow rate. The overall extra-column variance
      from the injection valve was found to vary from 34 to 23 nL. A new mathematical
      model was derived that explains this exponential contribution of extra-column
      variance on chromatographic performance. The chromatographic efficiency was
      compromised by ~130% for a non-retained analyte because of injection valve dead
      volume. The measured chromatographic efficiency was greatly improved when a new
      nano-flow pumping system with integrated injection valve was used.

PMID- 25591402
TI  - Optimization and evaluation of radially interconnected versus bifurcating flow
      distributors using computational fluid dynamics modelling.
AB  - Two main groups of flow distributors, viz. "bifurcating distributors" (BF) and
      "radially interconnected distributors" (RI), as well as some hybrid distributors
      were investigated. Computational fluid dynamics was used to evaluate the
      performance of the distributors and to establish the design yielding the most
      uniform velocity field and the smallest variance for the bands emerging from the
      distributor. A minimum channel width of 100 MUm was considered to allow the use
      of micro-milling techniques for chip fabrication. The main factors that
      influenced the values of band variances were identified. The performance of the
      distributors was found to correlate most strongly with the volume of the flow
      distributors. The separation bed should be positioned immediately after, but not
      against the flow distributor. It was concluded that BF distributors perform best
      in terms of band variance. The values of band variances for the BF distributor
      decreased with increasing angle between bifurcation branches and the lowest value
      of about 0.01 mm(2) was found for alpha=175 degrees . Both BF and RI flow
      distributors were found to perform reasonably well when imperfections were
      present in the structure. However, severe blockages (exceeding 75% of the cross
      sectional area and length) of channels in, especially, BF flow distributors may
      jeopardize their performance.

PMID- 25591401
TI  - Using the liquid-chromatographic-fingerprint of sterols fraction to discriminate
      virgin olive from other edible oils.
AB  - A method to discriminate virgin olive oil from other edible vegetable oils such
      as, sunflower, pomace olive, rapeseed, canola, corn and soybean, applying
      chemometric techniques to the liquid chromatographic representative fingerprint
      of sterols fraction, is proposed. After a pre-treatment of the LC chromatogram
      data - including baseline correction, smoothing signal and mean centering -
      different unsupervised and supervised pattern recognition procedures, such as
      principal component analysis (PCA), hierarchical cluster analysis (HCA), and
      partial least squares-discriminant analysis (PLSDA), have been applied. From the
      information obtained from PCA and HCA, two groups can be clearly distinguished
      (virgin olive and the rest of vegetable oils tested) which have been used to
      discriminate between two defined classes by means of a PLSDA model. Five latent
      variables (LVs) explained 76.88% of X-block variance and 95.47% of the defined
      classes block (gamma-block) variance. A root mean square error for calibration
      and cross validation of 0.10 and 0.22 respectively, confirmed these results and a
      root mean square error for prediction of 0.15 evidences that the classification
      model proposed presents an adequate prediction capability. The contingency table
      also shows the good performance of the model, proving the capability of the LC-R
      FpM, to discriminate virgin olive from other vegetable edible oils.

PMID- 25591403
TI  - Gaining insight in the behaviour of imidazolium-based ionic liquids as additives
      in reversed-phase liquid chromatography for the analysis of basic compounds.
AB  - In reversed-phase liquid chromatography in the absence of additives, cationic
      basic compounds give rise to broad and asymmetrical peaks as a result of ionic
      interactions with residual free silanols on silica-based stationary phases. Ionic
      liquids (ILs), added to the mobile phase, have been suggested as alternatives to
      amines to block the activity of silanols. However, the dual character of ILs
      should be considered: both cation and anion may be adsorbed on the stationary
      phase, thereby creating a double asymmetrical layer positively or negatively
      charged, depending on the relative adsorption of both ions. In this work, a study
      of the performance of six imidazolium-based ILs (the chlorides and
      tetrafluoroborates of 1-ethyl-, 1-butyl- and 1-hexyl-3-methylimidazolium) as
      modifiers of the chromatographic behaviour of a group of 10 beta-blockers is
      performed, and compared with triethylamine and dimethyloctylamine. In order to
      gain more insight in the behaviour of ILs in RPLC, the changes in the nature of
      the chromatographic system, at increasing concentration of the additives, were
      followed based on retention and peak shape modelling. The multiple interactions
      that amines and ILs experience inside the chromatographic system suggest that the
      suppressing potency should be measured based on the shape of chromatographic
      peaks and not on the changes in retention. The ILs 1-hexyl-3-methyl-imidazolium
      chloride and tetrafluoroborate offered the most interesting features for the
      separation of the basic drugs. 

PMID- 25591404
TI  - Preparative separation and identification of novel subsidiary colors of the color
      additive D&C Red No. 33 (Acid Red 33) using spiral high-speed counter-current
      chromatography.
AB  - Three low-level subsidiary color impurities (A, B, and C) often present in
      batches of the color additive D&C Red No. 33 (R33, Acid Red 33, Colour Index No.
      17200) were separated from a portion of R33 by spiral high-speed counter-current
      chromatography (HSCCC). The separation involved use of a very polar solvent
      system, 1-BuOH/5mM aq. (NH4)2SO4. Addition of ammonium sulfate to the lower phase
      forced partition of the components into the upper phase, thereby eliminating the
      need to add a hydrophobic counterion as was previously required for separations
      of components from sulfonated dyes. The very polar solvent system used would not
      have been retained in a conventional multi-layer coil HSCCC instrument, but the
      spiral configuration enabled retention of the stationary phase, and thus, the
      separation was possible. A 1g portion of R33 enriched in A, B, and C was
      separated using the upper phase of the solvent system as the mobile phase. The
      retention of the stationary phase was 38.1%, and the separation resulted in 4.8
      mg of A of >90% purity, 18.3mg of B of >85% purity, and 91 mg of C of 65-72%
      purity. A second separation of a portion of the C mixture resulted in 7 mg of C
      of >94% purity. The separated impurities were identified by high-resolution mass
      spectrometry and NMR spectroscopic techniques as follows: 5-amino-3-biphenyl-3
      ylazo-4-hydroxy-naphthalene-2,7-disulfonic acid, A; 5-amino-4-hydroxy-6-phenyl-3
      phenylazo-naphthalene-2,7-disulfonic acid, B; and 5-amino-4-hydroxy-3,6-bis
      phenylazo-naphthalene-2,7-disulfonic acid, C. The isomers A and B are compounds
      reported for the first time. Application of the spiral HSCCC method resulted in
      the additional benefit of yielding 930 mg of the main component of R33, 5-amino-4
      hydroxy-3-phenylazo-naphthalene-2,7-disulfonic acid, of >97% purity.

PMID- 25591405
TI  - The effects of farm management practices on liver fluke prevalence and the
      current internal parasite control measures employed on Irish dairy farms.
AB  - Fasciolosis caused by Fasciola hepatica is responsible for major production
      losses in cattle farms. The objectives of this study were to assess the effect of
      farm management practices on liver fluke prevalence on Irish dairy farms and to
      document the current control measures against parasitic diseases. In total, 369
      dairy farms throughout Ireland were sampled from October to December 2013, each
      providing a single bulk tank milk (BTM) sample for liver fluke antibody-detection
      ELISA testing and completing a questionnaire on their farm management. The
      analysis of samples showed that cows on 78% (n=288) of dairy farms had been
      exposed to liver fluke. There was a difference (P<0.05) between farms where cows
      were positive or negative for liver fluke antibodies in (a) the total number of
      adult dairy cows in herds, (b) the number of adult dairy cows contributing to BTM
      samples, and (c) the size of the total area of grassland, with positive farms
      having larger numbers in each case. There was no difference (P>0.05) between
      positive and negative farms in (a) the grazing of dry cows together with
      replacement cows, (b) whether or not grazed grassland was mowed for conservation,
      (c) the type of drinking water provision system, (d) spreading of cattle manure
      on grassland or (e) for grazing season length (GSL; mean=262.5 days). Also, there
      were differences (P<0.001) between drainage statuses for GSL with farms on good
      drainage having longer GSL than moderately drained farms. The GSL for dairy cows
      on farms with good drainage was 11 days longer than for those with moderate
      drainage (P<0.001). The percentage of farmers that used an active ingredient
      during the non-lactating period against liver fluke, gastrointestinal nematodes,
      lungworm, and rumen fluke was 96%, 85%, 77% and 90%, respectively. Albendazole
      was the most frequently used active ingredient for treatment against
      gastrointestinal nematodes (57%), liver fluke (40%) and lungworm (47%),
      respectively. There was a difference (P<0.05) in the use of triclabendazole and
      albendazole between positive and negative farms, with triclabendazole use being
      more common in positive farms. This study highlighted differences in dairy
      management practices between Irish farms with dairy herds exposed or not exposed
      to liver fluke and stressed the need of fine-scale mapping of the disease
      patterns even at farm level to increase the accuracy of risk models. Also,
      comprehensive advice and professional support services to farmers on appropriate
      farm management practices are very important for an effective anthelmintic
      control strategy. 

PMID- 25591406
TI  - Molecular biological identification of Babesia, Theileria, and Anaplasma species
      in cattle in Egypt using PCR assays, gene sequence analysis and a novel DNA
      microarray.
AB  - In this preliminary study, a novel DNA microarray system was tested for the
      diagnosis of bovine piroplasmosis and anaplasmosis in comparison with microscopy
      and PCR assay results. In the Dakahlia Governorate, Egypt, 164 cattle were
      investigated for the presence of piroplasms and Anaplasma species. All
      investigated cattle were clinically examined. Blood samples were screened for the
      presence of blood parasites using microscopy and PCR assays. Seventy-one animals
      were acutely ill, whereas 93 were apparently healthy. In acutely ill cattle,
      Babesia/Theileria species (n=11) and Anaplasma marginale (n=10) were detected.
      Mixed infections with Babesia/Theileria spp. and A. marginale were present in two
      further cases. A. marginale infections were also detected in apparently healthy
      subjects (n=23). The results of PCR assays were confirmed by DNA sequencing. All
      samples that were positive by PCR for Babesia/Theileria spp. gave also positive
      results in the microarray analysis. The microarray chips identified Babesia bovis
      (n=12) and Babesia bigemina (n=2). Cattle with babesiosis were likely to have
      hemoglobinuria and nervous signs when compared to those with anaplasmosis that
      frequently had bloody feces. We conclude that clinical examination in combination
      with microscopy are still very useful in diagnosing acute cases of babesiosis and
      anaplasmosis, but a combination of molecular biological diagnostic assays will
      detect even asymptomatic carriers. In perspective, parallel detection of
      Babesia/Theileria spp. and A. marginale infections using a single microarray
      system will be a valuable improvement. 

PMID- 25591407
TI  - Elimination of schistosomiasis japonica from formerly endemic areas in
      mountainous regions of southern China using a praziquantel regimen.
AB  - Schistosomiasis japonica is a major public health problem in China. Domestic
      animals play a major role in the transmission of Schistosoma japonicum to humans.
      To better understand the epidemiology of schistosomiasis japonica in domestic
      animals in the mountainous areas of China, we performed a 5-year longitudinal
      study of schistosomiasis in cattle and horses in Yunnan Province from 2009 to
      2013. We also performed a concurrent drug-based intervention study in three
      settlement groups in Yunnan Province aimed at developing an effective means of
      controlling transmission in this region. The prevalence of infection in cattle
      fluctuated between 1.67% and 3.05% from 2009 to 2011, and monthly treatments of
      schistosome-positive animals reduced the prevalence to 0% (P<0.05) from 2012 to
      2013. Prior to the intervention, we found that schistosomiasis was prevalent from
      May to October, with the highest prevalence observed in June (10.00%). We
      surveyed for environmental schistosome contamination, and 94.29% of the miracidia
      found were from cattle. Our study showed that it is possible to eliminate
      schistosomiasis in domestic animals in the mountainous regions of China by
      monthly treating cattle and horses from schistosome-positive households from May
      to October. 

PMID- 25591408
TI  - Preliminary evaluation of Community-Led Total Sanitation for the control of
      Taenia solium cysticercosis in Katete District of Zambia.
AB  - Taenia solium taeniasis/cysticercosis is a zoonotic disease endemic in sub
      Saharan Africa. It is associated with poor sanitary practices, free-range pig
      husbandry and lack of disease awareness in endemic communities. A comparative
      research was conducted with pre and post-intervention assessments in nine
      villages to evaluate Community-Led Total Sanitation (CLTS) as an intervention
      measure for the control of porcine cysticercosis in Katete District in the
      Eastern Province of Zambia. Blood samples were collected from pigs for
      circulating antigen detection and a questionnaire focused on the household was
      administered to a total of 153 respondents whose pigs were examined (64 pre
      intervention, 89 post-intervention), in order to obtain information on general
      demographic characteristics, pig husbandry practices, sanitation practices and
      associated knowledge and awareness of T. solium infections. The first sampling
      was conducted prior to the implementation of the CLTS and second sampling eight
      months after triggering of CLTS in the selected villages. A total of 379 pig
      serum samples were examined using the B158/B60 Ag-ELISA to detect T. solium
      cysticercosis, 104 pre-intervention and 275 post-intervention, of which 14
      (13.5%) and 45 (16.4%) were positive, respectively. Wald test p-values were
      computed to assess significant differences in the variables of interest mentioned
      above for the pre and post CLTS. The research revealed that CLTS as a control
      measure did not significantly improve T. solium infections in pigs. The research
      also revealed that the sanitation practices and awareness of cysticercosis did
      not change. It is recommended that a longer term evaluation be undertaken when
      the villages have been declared open defaecation free. In addition, the research
      recommends that health education, mass drug treatment and pig vaccination be
      incorporated, as an essential component of prevention and control programmes for
      T. solium infections. 

PMID- 25591409
TI  - Use of autologous fat grafting for breast reconstruction: a systematic review
      with meta-analysis of oncological outcomes.
AB  - BACKGROUND: There is growing interest in the use of autologous fat grafting (AFG)
      for breast reconstruction. Concerns have been raised regarding its effectiveness
      and safety. OBJECTIVE: The primary objective was to determine the oncological,
      clinical, aesthetic and functional, patient reported, process and radiological
      outcomes of AFG. METHODS: A protocol was published on PROSPERO (CRD42013005254).
      Types of studies: All original studies. TYPES OF PARTICIPANTS: Women undergoing
      reconstruction after surgery for breast cancer. Types of Interventions: AFG
      techniques for reconstruction. Types of outcome measures: Oncological, clinical,
      aesthetic and functional, patient reported, process and radiological. Search
      terms and keywords: The search strategy was devised to find papers regarding AFG
      for breast reconstruction. DATA SOURCES: Electronic databases were searched from
      1st January 1986 to 31st March 2014 including: PubMed, MEDLINE, EMBASE, SCOPUS,
      The Cochrane Library, and clinical trial registries. Identification and selection
      of studies: Title and abstract screening and full text assessment undertaken
      separately by independent researchers. Data extraction, collection and
      management: Data extracted by two researchers and stored in a standardised
      database. RESULTS: 35 studies were included (3624 patients) with a high degree of
      patient and surgeon satisfaction over a mean of 1.9 sessions at 18 month follow
      up. Fat necrosis was the commonest reported complication (4.4%), biopsy of a
      subsequent breast lump was required in 2.7% and an interval mammogram in 11.5%.
      The weighted mean recurrence rate was 4.4% at 24.6 months. Meta-analysis of
      comparative studies showed no significant difference in oncological event rates
      between AFG and non-AFG groups (p=0.10). CONCLUSION: AFG is a potentially useful
      reconstructive tool, has a relatively low complication rate, with the majority of
      patients and clinicians satisfied or very satisfied with the results. Long term
      clinical and radiological follow-up is required. Further research is necessary to
      confirm oncological ramifications.

PMID- 25591410
TI  - Axillary lymph node dissection: do you know your boundaries?

PMID- 25591411
TI  - Primary health care and public health: foundations of universal health systems.
AB  - The aim of this review is to advocate for more integrated and universally
      accessible health systems, built on a foundation of primary health care and
      public health. The perspective outlined identified health systems as the frame of
      reference, clarified terminology and examined complementary perspectives on
      health. It explored the prospects for universal and integrated health systems
      from a global perspective, the role of healthy public policy in achieving
      population health and the value of the social-ecological model in guiding how
      best to align the components of an integrated health service. The importance of
      an ethical private sector in partnership with the public sector is recognized.
      Most health systems around the world, still heavily focused on illness, are doing
      relatively little to optimize health and minimize illness burdens, especially for
      vulnerable groups. This failure to improve the underlying conditions for health
      is compounded by insufficient allocation of resources to address priority needs
      with equity (universality, accessibility and affordability). Finally, public
      health and primary health care are the cornerstones of sustainable health
      systems, and this should be reflected in the health policies and professional
      education systems of all nations wishing to achieve a health system that is
      effective, equitable, efficient and affordable.

PMID- 25591412
TI  - Surgical assessment: measuring unobserved health.
AB  - BACKGROUND: The federal and provincial governments in Canada have invested an
      enormous amount of resources to measure, report and reduce surgical wait times.
      Yet these measures under-report the wait period that patients' actually
      experience, because they do not capture the length of time a patient spends
      waiting to see the surgeon for a surgical assessment. This unmeasured time is
      referred to as the "wait one" (W1). Little is known about W1 and the effects that
      this has on patients' health. Similarly, it is not understood whether patients
      waiting for surgical assessment actually want or need surgery. Existing
      administrative and clinical dataset do not capture information on health and
      decision-making while the patient is waiting for care form a specialist. The
      objective of this proposed study is to understand the impact that W1 for elective
      surgeries has on the health of patients and to determine whether this time can be
      reduced. METHODS/DESIGN: A prospective survey design will be used to measure the
      health of patients waiting for surgical assessment. Working with the support of
      the surgical specialities in Vancouver Coastal Health, we will survey patients
      immediately after being referred for surgical assessment, and every four months
      thereafter, until they are seen by the surgeon.Validated survey instruments will
      be used, including: generic and condition-specific health status questionnaires,
      pain and depression assessments. Other factors that will be measured include:
      patients' knowledge about their condition, and their desired autonomy in the
      decision making process. We have piloted data collection in one surgical
      specialty in order to demonstrate feasibility. DISCUSSION: The results from this
      study will be used to quantify changes in patients' health while they wait for
      surgical assessment. Based on this, policy- and decision-makers could design care
      interventions during W1, aimed at mitigating any negative health consequences
      associated with waiting. The results from this study will also be used to better
      understand whether there are factors that predict patients' desire to proceed to
      surgery. These could be used to guide future research into experimenting with
      interventions to minimize inappropriate referrals and where they are best
      targeted.

PMID- 25591413
TI  - Polypectomy practices of sub-centimeter polyps in the English Bowel Cancer
      Screening Programme.
AB  - BACKGROUND: Most colonic polyps are small, and several polypectomy techniques are
      available. We aimed to describe the variation in polypectomy techniques employed
      for the removal of sub-centimeter polyps in relation to polyp characteristics,
      completeness of histological excision and safety. METHODS: Prospectively
      collected data relating to the removal of sub-centimeter polyps over a 3-year
      period (between January 2010 and December 2012) were retrieved from the English
      Bowel Cancer Screening Programme. RESULTS: A total of 147,174 sub-centimeter
      polyps were removed during 62,679 procedures. For pedunculated polyps, hot snare
      was most common in the left (median 92 %, IQR 83.3-97.0 %) and right colon
      (median 75 %, IQR 3-92 %). For non-pedunculated polyps, cold snare was most
      common in the right colon (median 24 %, IQR 9-47 %); whereas hot snare remained
      most common in the left colon (median 32 %, IQR 19-49 %). Surgeons were more
      likely than physicians to use diathermy-assisted techniques (65.6 vs. 56.5 %, p <
      0.001). Twelve (0.03 %) bleeding episodes required transfusion with no
      polypectomy technique dominating and 16 (0.04 %) perforations with 81 % of
      polypectomies performed using diathermy-assisted techniques. There was
      substantial variation between screening centers for the completeness of
      histological excision. For non-pedunculated polyps, histologically confirmed
      complete excision was more after EMR (23.4 %) compared with other techniques
      (cold biopsy forceps 17.7 %, cold snare 15.1 %, hot biopsy forceps 19.1 %, hot
      snare 21.5 %). The use of cold techniques and EMR has increased over time,
      whereas the use of hot biopsy forceps and hot snare has decreased (p < 0.001).
      CONCLUSIONS: The removal of sub-centimeter polyps within the BCSP is safe despite
      wide variations in practice. The use of cold resection techniques and EMR has
      increased over time. The histological assessment for completeness of excision is
      limited and should be confirmed endoscopically at the time of polypectomy.

PMID- 25591414
TI  - [Intraoperative management of undetectable parathyroid adenoma].
AB  - Despite new technologies and progress in parathyroid gland imaging, missed
      parathyroid adenomas are still a problem. In reoperations most adenomas were
      found in eutopic positions. Adenoma in atypical positions were mostly situated in
      the thymus or in the esophageal-tracheal groove. Positive parathyroid imaging can
      be helpful but does not necessarily result in a better success rate than
      conventional bilateral exploration by an experienced surgeon, which is > 95 %.
      The knowledge of anatomy and embryological development of parathyroid glands is
      most important. Intraoperative determination of parathyroid hormone levels can
      help localize the site of the adenoma. Thyroid resection should only be performed
      if preoperative or intraoperative ultrasound indicates a tumor in the thyroid
      gland. The most important factor for a successful parathyroid operation is an
      experienced surgeon. 

PMID- 25591415
TI  - [Erratum to: The role of biomarkers in the diagnostics of acute mesenteric
      ischemia].

PMID- 25591416
TI  - [Pilon fractures. Part 1: Diagnostics, treatment strategies and approaches].
AB  - Intraarticular fractures of the distal tibia (pilon fractures) are caused by
      axial forces, usually in combination with torsional moments. Routine diagnostics
      include plain films and three dimensional (3D) imaging with computed tomography
      (CT). Treatment is often impaired by complex fracture configurations and thin
      soft tissue layers. The management of complex pilon fractures with soft tissue
      injuries has seen many trends, with changes toward staged protocols of temporary
      external fixation followed by delayed open reduction and internal fixation
      (ORIF), minimally invasive percutaneous plate osteosynthesis (MIPPO) techniques
      and special implants, the benefits of negative pressure wound sealing and early
      "fix and flap" efforts to reconstruct soft tissue defects. Reduction and fixation
      must involve respectful management and careful handling of soft tissues in order
      to minimize the well-known complications of this difficult fracture. The proper
      approach is one of the keys to success. Approach planning is based on the careful
      and thorough analysis of the fracture pattern in the 3D data set, which is the
      basis for a successful strategy for articular reconstruction. 

PMID- 25591417
TI  - [Dysplastic melanocytic nevus].
AB  - Dysplastic nevus is still a controversial entity both clinically and
      histologically. The occurrence of dysplastic nevus especially in the context of
      dysplastic nevus cell syndrome is associated with an increased risk for melanoma.
      The following minimal histological criteria should be fulfilled: nests of
      melanocytes varying in size and shape, bridging and confluent, proliferation of
      single melanocytes basal and suprabasal, cytoplasmic and nuclear atypia of
      melanocytes and subepidermal fibroplasia. The biological behavior (common nevus
      variant or precursor of melanoma?) is difficult to evaluate by presently
      available methods. The further development of new molecular biology techniques
      may allow a better prognosis of dysplastic nevi in an objective and reproducible
      manner. Against this background complete excision followed by clinical
      surveillance has to be recommended for the routine practice. 

PMID- 25591418
TI  - Density of the cerebral cortex in computed tomography angiography source images
      and clinical outcomes in Grade V subarachnoid hemorrhage.
AB  - OBJECTIVE: Among patients diagnosed with Grade V subarachnoid hemorrhage (SAH)
      according to the World Federation of Neurosurgical Societies (WFNS), the
      identification of those with the possibility of recovery is not feasible,
      although approximately one-fifth of these patients have favorable outcomes
      according to a recently published series of surgical papers. We hypothesized that
      computed tomography angiography (CTA) source images (SIs), which have applied to
      the detection of acute ischemia, might be useful for selecting Grade V patients
      with possibilities for favorable outcomes. METHODS: We retrospectively assessed
      170 SAH patients who underwent surgery between January 2009 and February 2012 and
      quantitatively measured their mean cerebral cortical densities from the initial
      CTA-SIs. RESULTS: The cortical densities of 123 patients of Grades I-IV were
      strongly affected by the following two CTA-SI findings that were revealed by
      multivariate analysis: the density of the internal carotid artery (ICA) just
      proximal to the petrous portion and the ratio of the subarachnoid (SA) space to
      intracranial volume (P < 0.05). Favorable outcomes were obtained in 9 of the 47
      Grade V patients (19.1%), and the predictors of the favorable outcomes according
      to multivariate analysis were increased cortical densities on the CTA-SIs and
      female patients (P < 0.05). CONCLUSION: The outcomes of Grade V patients could be
      partly predicted based on the estimates of cortical density from the CTA-SIs, and
      this measure might be useful for the selection of Grade V patients for surgery,
      provided that both ICA density and SA space ratio are confirmed before the
      evaluation of cortical density.

PMID- 25591420
TI  - Cerebral venous sinus thrombosis may be associated with hepatitis B virus
      infection: a preliminary finding.
AB  - OBJECTIVE: To assess the clinical significance of hepatitis B virus (HBV)
      infection in patients with cerebral venous sinus thrombosis (CVST). METHODS:
      Twenty-two patients with CVST confirmed by magnetic resonance venography (MRV) or
      digital subtraction angiography (DSA) and 743 controls with ischemic stroke
      confirmed by magnetic resonance imaging (MRI) were analyzed retrospectively.
      RESULTS: Among all researches, HBV surface antigen (HBsAg)-positive rate was
      high. Six of the 22 (27.3%) confirmed cases had HBsAg. However, HBsAg-positive
      rate in patients with ischemic stroke was only 45 of the 743 cases (6.1%), closed
      to the average prevalence in China (~ 8.6%), but much lower than the positive
      rate in CVST patients (27.3 vs 6.1%, P  =  0.002). Odd ratio (OR) value between
      HBsAg-positive CVST patients (27.3%) and HBsAg-positive ischemic stroke patients
      (6.1%) was 5.78. The OR value between HBsAg-positive CVST patients (27.3%) and
      average prevalence of HBV infection in China (8.6%) was nearly 3.99. It meant
      that HBV infection might be a risk factor for CVST. However, there existed no
      statistically significant difference in HBV surface antibody (HBsAb), HBV e
      antigen (HBeAg), HBV e antibody (HBeAb), and HBV central antibody (HBcAb)
      positive rate. The HBV surface antigen (HBsAg)-positive CVST patients did not
      show worse liver function. Most of them were inactive HBV carriers. CONCLUSION:
      Hepatitis B virus infection may be a risk factor for CVST.

PMID- 25591419
TI  - Protective effect of telmisartan on neurovascular unit and inflammasome in stroke
      resistant spontaneously hypertensive rats.
AB  - OBJECTIVES: Hypertension is a crucial risk factor for both stroke and dementia,
      including Alzheimer's disease (AD). We inspected the effect of telmisartan on the
      neurovascular unit (NVU) and related inflammatory responses in spontaneously
      hypertensive rat stroke resistant (SHR-SR) by observing the components of NVU
      such as N-acetyl glucosamine oligomer (NAGO), collagen IV, astrocytes, and matrix
      metalloproteinase-9 (MMP-9), as well as inflammasome NOD-like receptors family
      protein 3 (NLRP3). METHODS: In the present study, we examined the effect of a
      highly selective angiotensin type 1 (AT-1) antagonist of angiotensin 2 receptor
      with high lipid solubility, telmisartan, on NVU and related inflammatory
      responses in SHR-SR with a low dose (0.3 mg/kg/day) only for improving metabolic
      syndrome, and a high dose (3 mg/kg/day) for improving both metabolic syndrome and
      SHR-SR hypertension. RESULTS: Compared to normotensive Wistar rats, long-lasting
      hypertension in SHR-SR disrupted NVU by changing immunohistological components
      such as NAGO, collagen IV, astrocytes, and MMP-9. SHR-SR also strongly induced AD
      related inflammasome NLRP3 in neuronal cells with age. However, such NVU
      disruption and inflammasome activation were greatly improved with dose-dependent
      telmisartan treatments. DISCUSSION: These results suggest that telmisartan
      comprehensively protected the NVU components by reducing inflammatory reactions
      relative to AD in hypertensive rats, which could also preclude the risk of AD
      under hypertension.

PMID- 25591421
TI  - Influence of internal carotid artery stenosis, blood pressure, glycated
      hemoglobin, and hemoglobin level on fMRI signals of stroke patients.
AB  - OBJECTIVES: To identify the effect of internal carotid artery (ICA) stenosis,
      blood pressure (BP), glycated hemoglobin (HbA1c), and hemoglobin level on blood
      oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI)
      signals in stroke patients. METHODS: A total of 18 stroke patients with acute
      cerebral infarction (13 males and 5 females) and 13 age-matched healthy controls
      (5 males and 8 females) were recruited. Among 18 stroke patients, 8 had
      significant ICA stenosis (> 50%) and 10 had nonsignificant ICA stenosis (< 50%).
      During handgrip task, stroke patients and normal controls were allowed to use
      their hands coincided with infarction and right hands, respectively. RESULTS: The
      mean BOLD signals in patients with significant ICA stenosis were significantly
      less than that in patients with nonsignificant ICA stenosis. Mean arterial
      pressure (MAP) was significantly correlated with activated voxels of Brodmann
      area 4 (P < 0.01) and total activated voxels (P  =  0.007), whereas hemoglobin
      and HbA1c showed no significant correlation with activated voxels of Brodmann
      area 4 or total activated voxels (P > 0.05). CONCLUSION: It is suggested that
      both ICA stenosis and arterial BP could influence BOLD signal, while HbA1c and
      hemoglobin level had no effect on BOLD signal.

PMID- 25591422
TI  - Neuroprotective effects of pretreatment with macrolide antibiotics on cerebral
      ischemia reperfusion injury.
AB  - OBJECTIVE: This study aims to determine if macrolide antibiotics have
      neuroprotective effects against transient cerebral ischemia. METHODS: Sprague
      Dawley rats were subjected to cerebral ischemia for 90 minutes followed by 24 or
      72 hours of reperfusion. An oral suspension of roxithromycin (RXM),
      clarithromycin (CAM), erythromycin (EM), azithromycin (AZM), or kitasamycin (INN)
      was given at 10 or 100 mg/kg for 7 days before ischemia. The infarct volume,
      edema volume, and neurological performance were evaluated after 24 and 72 hours
      of reperfusion. The cerebral blood flow (CBF) was measured with a magnetic
      resonance imaging (MRI) system after 90 minutes of ischemia. Another experiment
      was conducted to investigate how the ischemic injury was affected by the interval
      from the antibiotic pretreatment to the ischemia in rats pretreated with CAM.
      RESULTS: Roxithromycin, CAM, AZM, and INN significantly reduced the infarct
      volume in the high-dose group after 24 and 72 hours of reperfusion. All of the
      agents significantly decreased the edema in the high-dose groups at 24 and 72
      hours, while only CAM and AZM significantly reduced the edema volume in the low
      dose groups at 24 hours. All of the macrolide antibiotics at the high dose
      significantly improved neurological deficit scores at 24 and 72 hours. There were
      no differences in the CBF between the vehicle and respective antibiotic groups.
      In the experiment examining the interval, the 24-hour interval group exhibited
      the strongest neuroprotective effect. DISCUSSION: These results demonstrate that
      the macrolide antibiotics RXM, CAM, EM, AZM, and INN may confer neuroprotective
      effects against ischemic damage following cerebral ischemia without affecting the
      CBF.

PMID- 25591423
TI  - Paraneoplastic nerve hyperexcitability.
AB  - OBJECTIVES: To provide an overview of paraneoplastic nerve hyperexcitability
      syndromes. METHODS: An extensive review of the literature on nerve
      hyperexcitability was performed. Particular attention was paid to Isaacs'
      syndrome and Morvan's syndrome, as well as their relationship to neoplasia.
      RESULTS: An overview of the history, clinical manifestations (including
      neurophysiologic findings), pathophysiology, and management is presented.
      Clinical differences between the exclusively peripheral nervous system involving
      Isaacs' syndrome and Morvan's syndrome, which also involves the central nervous
      system (CNS) are detailed. The role of immune-mediated dysfunction of specific
      components of the voltage-gated potassium channel (VGKC) complex in the
      pathophysiology of these syndromes is explained. Finally, the limited data on
      management of these syndromes, including the use of antiepileptic and
      immunomodulatory therapies are discussed. CONCLUSION: Nerve hyperexcitability
      syndrome represents a spectrum of neuroimmunologic diseases, which are often
      paraneoplastic in etiology.

PMID- 25591424
TI  - AS1069562, the (+)-isomer of indeloxazine, exerts analgesic effects in rat models
      of nociceptive pain.
AB  - OBJECTIVES: The (+)-isomer of indeloxazine AS1069562 has multiple pharmacological
      actions, such as serotonin (5-HIT) and norepinephrine (NE) reuptake inhibition
      and analgesic effects in animal models of neuropathic pain. Here, we investigated
      the analgesic effects of AS1069562 in rat models of inflammatory and
      noninflammatory nociceptive pain. METHODS: Adjuvant-induced arthritis (AIA) and
      bradykinin-induced knee joint pain were used as rat models of inflammatory pain.
      The chronic phase of monoiodoacetate-induced arthritis (MIA) was used as a rat
      model of noninflammatory pain. Analgesic effects were evaluated by weight-bearing
      deficit in the AIA and MIA models and by pain response in the bradykinin-induced
      knee joint pain model. RESULTS: In the AIA model and the bradykinin-induced knee
      joint pain model, AS1069562 significantly ameliorated the pain-related behavior
      of weight-bearing deficit and the pain response, respectively. AS1069562 also
      significantly improved the pain-related behavior of weight-bearing deficit in the
      chronic phase of the MIA model. Further, following monoiodoacetate injection,
      repeated administration of AS1069562 or duloxetine significantly improved weight
      bearing deficit in the MIA model. Interestingly, the analgesic effect of
      AS1069562 was sustained for 24 hours after the last administration, although the
      plasma concentration of AS1069562 was reduced to undetectable levels. In
      contrast, the analgesic effect of duloxetine did not continue after treatment
      discontinuation. DISCUSSION: AS1069562 exerts analgesic effects on inflammatory
      and noninflammatory nociceptive pain in rat models of arthritis pain, and
      repeated administration of AS1069562 exerts a more persistent analgesic effect on
      arthritis pain than duloxetine. These findings suggest that AS1069562 has an
      attractive analgesic profile for the treatment of nociceptive pain.

PMID- 25591425
TI  - Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene
      (MTHFR gene) with ischemic stroke: a meta-analysis.
AB  - OBJECTIVE: Studies on association between methylenetetrahydrofolate reductase
      gene (MTHFR) C677T gene polymorphism and ischemic stroke have shown conflicting
      results. We have conducted a meta-analysis to determine the precise association
      of the C677T polymorphism of MTHFR gene with risk of ischemic stroke. MATERIALS
      AND METHODS: We searched electronic databases Medline, EMBASE, and Google Scholar
      (last search dated till August 2014). Pooled odds ratios (ORs) with 95%
      confidence intervals (CIs) from random or fixed-effects models were calculated.
      The methodological quality of included studies was determined by the quality
      assessment scale. RESULTS: Thirty eight case-control studies fulfilled our
      inclusion criteria comprising 6310 patients and 8297 controls. The significant
      associations between MTHFR C677T genetic polymorphism and risk of ischemic stroke
      were observed in dominant (OR, 1.09; 95% CI, 1.06-1.12, P-value < 0.001) and
      recessive (OR, 1.31; 95% CI, 1.19-1.44, P-value < 0.001) inheritance models. In
      an Asian population, significant association between the MTHFR polymorphism and
      ischemic stroke was observed (dominant model: OR 1.36, 95% CI 1.23-1.49 and under
      recessive model OR, 1.29; 95% CI, 1.15-1.45). In the Caucasian population
      borderline, non-significant association was observed under dominant model of
      inheritance (OR, 1.05; 95% CI, 0.99-1.10) but significant association was
      observed under the recessive model of inheritance (OR, 1.33; 95% CI, 1.13-1.58).
      CONCLUSION: The present study results suggest that MTHFR C677T genetic
      polymorphism is a probable risk of ischemic stroke.

PMID- 25591426
TI  - Reliability of the witness descriptions of epileptic seizures and psychogenic non
      epileptic attacks: a comparative analysis.
AB  - BACKGROUND: The diagnosis of epilepsy primarily depends on description of the
      observed seizure. The aim of this study was to determine the reliability of
      witness' description among groups with different medical education. METHODS: A
      group of 44 respondents (15 laymen, 15 medical students, and 14 doctors at
      neurology residency program) were shown video footages of focal epileptic seizure
      (ES) with secondary generalization and psychogenic non-epileptic seizure (PNES)
      of the same patient. The ability to describe ES and PNES characteristics, to
      estimate duration of seizures, and to detect of accurate seizure type was
      evaluated using a questionnaire. For the analysis of primary data obtained from
      questionnaires, we used descriptive statistical methods and methods for testing
      statistical hypotheses. RESULTS: The sensitivity (Sn) and specificity (Sp) for
      accurate recognition of ES are different in the examined groups (laymen Sn  = 
      53.3%, Sp  =  33.3%; medical students Sn  =  100%, Sp  =  13.3%; neurology
      residents Sn  =  100%, Sp  =  71.4%). Evaluated duration of PNES and ES do not
      differ between examined groups. The impression that ES and PNES are distinct
      events is reciprocal for medical students and neurology residents, but not in
      laymen group. Neurology residents notice the essential characteristics of ES in
      high percentage. CONCLUSION: Accurate classification of the attacks is associated
      with the observers' level of medical knowledge. Witnesses with specific,
      neurological knowledge with higher probability, compared to the laity and medical
      students, differentiate ES from PNES.

PMID- 25591427
TI  - [Target and destination in the management of critical illnesses].

PMID- 25591428
TI  - [Update of critical care medicine 2014: retrospection and prospect].

PMID- 25591429
TI  - [Reunderstanding and prospect of treatment of septic shock with anisodamine].

PMID- 25591430
TI  - [Influence of fluid loading in patients at different stages of septic shock: a
      prospective study].
AB  - OBJECTIVE: To explore the influence of fluid loading at different stages in
      patients with septic shock. METHODS: A prospective study was conducted. Forty-two
      mechanically ventilated patients in septic shock were enrolled in the Department
      of Critical Care Medicine of the Fourth People's Hospital of Shenyang from March
      2010 to March 2014. Fluid loading was performed at 0, 24, 48 and 72 hours after
      the diagnosis of septic shock. The hemodynamic parameters including cardiac
      output ( CO ), stroke volume ( SV ), and extravascular lung water index ( EVLWI )
      were measured by pulse indicator continuous cardiac output ( PiCCO ), and
      arterial partial pressure ( PaO2 ) was determined. Positive responders were
      defined as SV increased by more than 15% after fluid loading. Increase of lung
      water was defined as EVLWI increased after fluid loading and its value was more
      than 7 mL/kg. Oxygenation descend was defined when oxygenation index ( PaO2/FiO2
      ) lowered. Fluid responsiveness, extravascular lung water, and oxygenation were
      analyzed and recorded at different stages in patients with septic shock. RESULTS:
      Fluid loading test was conducted for a total of 168 times in 42 patients.
      Compared with those before fluid loading test, the heart rate ( HR ) was lowered,
      and mean arterial pressure ( MAP ), CO, and SV were increased after fluid loading
      at 0, 24, 48 hours ( all P<0.01),unchanged at 72 hours. EVLWI levels at all time
      points were increased including an increase of EVLWI less than 7 mL/kg at 0 hour
      and 24 hours, and higher than 7 mL/kg at 48 hours and 72 hours [ EVLWI ( mL/kg )
      at 0 hour: 6.0+/-1.5 vs. 4.7+/-1.5, t = -4.183, P = 0.000; 24 hours: 6.5+/-1.5
      vs. 5.6+/-1.3, t = -6.000, P = 0.000; 48 hours: 8.1+/-2.2 vs. 6.1+/-1.7, t = 
      7.246, P = 0.000; 72 hours: 9.0+/-2.4 vs. 6.2+/-1.5, t = -7.524, P = 0.000 ].
      After fluid loading, PaO2/FiO2 was increased remarkably at 0 hour and 24 hours,
      unchanged at 48 hours, and decreased significantly at 72 hours [ PaO2/FiO2 (
      mmHg, 1 mmHg = 0.133 kPa ) at 0 hour: 189.6+/-34.5 vs. 183.2+/-36.6, t = -3.644,
      P = 0.002; 24 hours: 194.6+/-35.7 vs. 190.7+/-37.5, t = -4.594, P = 0.000; 48
      hours: 201.8+/-30.2 vs. 200.8+/-33.0, t = -0.793, P=0.437; 72 hours: 201.7+/-24.8
      vs. 206.2+/-26.9, t = 2.243, P = 0.036 ]. The rate of positive response gradually
      decreased: 85.7%, 80.9%, 42.8%, 28.6% at 0, 24, 48, and 72 hours, the rate of
      lung water increased was gradually elevated: 9.8%, 14.3%, 42.8%, 61.9% at 0, 24,
      48, and 72 hours, and there was an increase of rate of lowering oxygenation with
      elapse of time ( 9.5%, 11.9%, 19.0%, 33.3% at 0, 24, 48 and 72 hours ). Compared
      with 0 hour, the rate of positive response decreased and rate of lung water
      increased were increased from 48 hours on ( P<0.05 or P<0.01 ), and rate of
      lowering oxygenation was increased at 72 hours ( P<0.01 ). CONCLUSIONS: 48 to 72
      hours might be the crucial period of occurrence of volume overload in patients
      with septic shock. Curtailing fluid infusion during this period might reduce the
      occurrence of pulmonary edema.

PMID- 25591431
TI  - [A prospective clinical study of pleth variability index in prediction of volume
      responsiveness in patients with septic shock].
AB  - OBJECTIVE: To evaluate the role of pleth variability index ( PVI ) by passive leg
      raising ( PLR ) test in volume responsiveness and volume status prediction in
      patients with septic shock. METHODS: A prospective randomized controlled trial (
      RCT ) was conducted. Eighty-seven patients suffering from septic shock undergoing
      mechanical ventilation in Department of Critical Care Medicine of Subei People's
      Hospital from June 2012 to September 2014 were enrolled. The hemodynamic changes
      before and after PLR were monitored by pulse indicated continuous cardiac output
      ( PiCCO ) and PVI monitoring. Responsive group: positive fluid response was
      defined as an increase in cardiac index ( CI )>=10% after PLR. Unresponsive
      group: negative fluid response was defined as an increase in CI<10% after PLR.
      The hemodynamic parameters, including heart rate ( HR ), mean arterial pressure (
      MAP ), central venous pressure ( CVP ), stroke volume variation ( SVV ), CI and
      PVI, and the changes in cardiac parameters (DeltaHR, DeltaMAP, DeltaCVP,
      DeltaSVV, DeltaCI, and DeltaPVI ) before and after PLR were determined. The
      relations between hemodynamic parameters and their changes with DeltaCI were
      analyzed by the Pearson analysis. The role of the parameters for volume
      responsiveness prediction was evaluated by receiver operating characteristic (
      ROC ) curves. RESULTS: 145 PLRs in 87 patients with septic shock were conducted,
      with 67 in responsive group and 78 in unresponsive group. There were no
      statistically significant differences in HR, MAP, CVP and CI before PLR between
      the responsive and unresponsive groups. SVV and PVI in responsive group were
      significantly higher than those in the unresponsive group [ SVV: ( 16.9+/-3.1 )%
      vs. ( 8.4+/-2.2 ) %, t = 9.078, P = 0.031; PVI: ( 20.6+/-4.3 )% vs. ( 11.1+/-3.2
      )%, t = 19.189, P = 0.022 ]. There were no statistically significant differences
      in HR, MAP, CVP, SVV, and PVI after PLR between the responsive group and
      unresponsive group. CI in the responsive group was significantly higher than that
      in the unresponsive group ( mL*s(-1)*m(-2): 78.3+/-6.7 vs. 60.0+/-8.3, t = 2.902,
      P = 0.025 ). There were no statistically significant differences in DeltaHR,
      DeltaMAP, DeltaCVP between responsive group and unresponsive group. DeltaSVV,
      DeltaCI and DeltaPVI in responsive group were significantly higher than those in
      the unresponsive group [ DeltaSVV: ( 4.6+/-1.5 )% vs. ( 1.8+/-0.9 )%, t = 11.187,
      P = 0.022; DeltaCI ( mL*s(-1)*m(-2) ): 18.3+/-1.7 vs. 1.7+/-0.5, t = 3.696, P =
      0.014; DeltaPVI: ( 6.4+/-1.1 )% vs. ( 1.3+/-0.2 )%, t = 19.563, P = 0.013 ]. No
      significant correlation between HR, MAP or CVP before PLR and DeltaCI was found.
      SVV ( r = 0.850, P = 0.015 ) and PVI ( r = 0.867, P = 0.001 ) before PLR were
      correlated with DeltaCI. It was shown by ROC curve that the area under ROC curve
      ( AUC ) for SVV fluid responsiveness prediction was 0.948, and cut-off of SVV was
      12.4%, the sensitivity was 85.4%, and specificity was 86.6%. The AUC for PVI
      fluid responsiveness prediction was 0.957, and cut-off was 14.8%, the sensitivity
      was 87.5%, and specificity was 84.8%. It was higher than other hemodynamic
      parameters ( HR, MAP, CVP ). CONCLUSIONS: PVI and SVV can better predict fluid
      responsiveness in mechanically ventilating patients with septic shock after PLR.
      PVI as a new continuous, noninvasive and functional hemodynamic parameter has the
      same accuracy as SVV.

PMID- 25591432
TI  - [Value of pulse indicator continuous cardiac output monitoring of cardiac
      function in septic shock patients: a prospective study].
AB  - OBJECTIVE: To investigate the value of employing pulse indicator continuous
      cardiac output ( PiCCO ) for cardiac function monitoring in patients with severe
      septic shock. METHODS: A prospective observation was conducted. Thirty-six septic
      shock patients in Department of Critical Care Medicine of Peking University Third
      Hospital admitted from August 2011 to December 2013 were enrolled. According to
      the degree of severity, the patients were divided into PiCCO monitor group and
      routine monitor group. The PiCCO monitor provided a continuous assessment of
      fluid resuscitation, vasopressors and inotropes infusion in the patients with
      severe septic shock. The following cardiac function parameters were assessed in
      severe septic shock patients on the 1st and 3rd day after intensive care unit (
      ICU ) admission: cardiac index ( CI ), global ejection fraction ( GEF ), rate of
      left ventricular pressure increase ( dp/dt max ), echocardiography, and blood
      troponin T ( TNT ) and B-type natriuretic peptide ( BNP ). The central venous
      pressure ( CVP ), mean arterial pressure ( MAP ) and the time reaching their
      standard values, and the norepinephrine dosage and 3-day fluid balance in severe
      septic shock patients were compared between milrinone and non-milrinone usage
      groups. The severity degree and outcome were compared between PiCCO monitor group
      and routine monitor group. RESULTS: There were 15 patients in PiCCO monitor group
      and 21 in routine monitor group among 36 septic shock patients. (1) In 15
      patients with PiCCO monitoring, the patients with decreased CI, GEF, and dp/dt
      max accounted for 40.0%, 93.3%, and 33.3% at 1 day after ICU admission, and
      accounted for 60.0%, 93.3%, and 60.0% at 3 days after ICU admission, and it
      showed that CI, GEF, and dp/dt max was not improved at 3 days after ICU
      admission. Echocardiography showed that 35.7% patients had lower left ventricular
      ejection fraction ( LVEF ) at 1 day after ICU admission, 71.4% and 71.4% of
      patients, respectively, had lower early diastolic mitral flow velocity/early
      diastolic myocardial velocity ( E/Em ) and early diastolic mitral flow
      velocity/end diastolic mitral flow velocity ( E/A ). Three days after ICU
      admission, 80% of patients with low LVEF value turned to normal, and diastolic
      dysfunction was ameliorated in 50% patients. At 1 day after ICU admission, higher
      TNT was found in 92.9% of patients, higher BNP in 100% of patients, and 3 days
      after ICU admission, 71.4% and 78.6% patients showed a decrease in TNT and BNP,
      respectively. (2) In PiCCO monitor group, there were no significant differences
      in initial CVP, MAP and their time reaching standard values, norepinephrine
      dosage between milrinone group ( n = 8 ) and non-milrinone group ( n = 7 ).
      However, 3-day intake of liquid in milrinone group was significantly higher than
      that in non-milrinone group ( mL: 8 324+/-3 962 vs. 4 372+/-2 081, t = -2.362, P
      = 0.034 ). (3) Compared with routine monitor group, there was a significant
      elevation in acute physiology and chronic health evaluation II ( APACHEII) score,
      sequential organ failure assessment ( SOFA ) score, duration of mechanical
      ventilation, length of ICU stay and 28-day hospital mortality in PiCCO monitor
      group [ APACHEII score: 20.67+/-6.15 vs. 14.71+/-4.67, t = -3.304, P = 0.002;
      SOFA score: 9.53+/-3.00 vs. 7.52+/-1.97, t = -2.433, P = 0.020; duration of
      mechanical ventilation ( hours ): 132 ( 54-310 ) vs. 63 ( 14-284 ), Z = -2.295, P
      = 0.022; length of ICU stay ( days ): 7 ( 4-15 ) vs. 5 ( 1-14 ), Z = -2.360, P =
      0.018; 28-day hospital mortality: 26.7% vs. 0, P = 0.023 ]. CONCLUSIONS: With the
      use of the PiCCO hemodynamic monitoring in patients with severe septic shock,
      more comprehensive values of blood volume, systemic vascular resistance and
      cardiac function can be obtained for guiding fluid resuscitation and selection of
      vasopressor and inotropic drugs.

PMID- 25591433
TI  - [The influence of hydroxyethyl starch on exogenous coagulation and active protein
      C in patients with septic shock].
AB  - OBJECTIVE: To investigate the influence of hydroxyethyl starch solution on
      exogenous coagulation and active protein C ( APC ) in the patients with septic
      shock. METHODS: A single-center prospective study was conducted. Eighty-four
      consecutive patients with septic shock admitted to intensive care unit ( ICU ) of
      Peking University People's Hospital from November 2009 to October 2014 were
      enrolled. The patients were randomized into two study groups by random digits
      table: Ringer lactate solution group ( RL group, n = 40 ) and hydroxyethyl starch
      group ( HES group, n = 44 ), and Ringer lactate solution or hydroxyethl starch
      130/0.4 was used for resuscitation respectively. Peripheral blood was collected
      at four time points: before resuscitation, 6, 12, and 24 hours after
      resuscitation. The prothrombin time ( PT ), tissue factor ( TF ), tissue factor
      pathway inhibitor ( TFPI ) and APC were determined, and the length of ICU stay
      and the mortality were recorded. RESULTS: There were no significant differences
      in PT, TF, TFPI, and APC before and after resuscitation in RL group. No change in
      PT was found after resuscitation in HES group, and no significant difference was
      found as compared with RL group. TF after resuscitation in HES group was
      decreased gradually, and the level at the 24 hours after resuscitation was
      significantly lower than that before resuscitation ( U/L: 15.80+/-7.32 vs.
      31.40+/-2.75, P<0.05 ); but there was no significant difference at all time
      points when compared with that of RL group ( all P>0.05 ). TFPI at 12 hours and
      24 hours after resuscitation in HES group was increased when compared with before
      resuscitation ( MUg/L: 1.32+/-0.22, 1.14+/-0.09 vs. 0.63+/-0.54 ). TFPI in HES
      group was significantly higher than that in RL group ( MUg/L: 0.84+/-0.69, 0.95+/
      0.30 ), but there was no significant differences between two groups ( both P>0.05
      ). APC after resuscitation in HES group was decreased gradually, which was
      significantly lower than that in RL group at 6, 12, 24 hours after resuscitation
      ( mg/L: 3.38+/-3.00 vs. 5.98+/-4.12, 3.31+/-1.94 vs. 5.33+/-3.71, 3.42+/-2.64 vs.
      7.53+/-4.67, P<0.05 or P<0.01 ). The length of ICU stay in HES group was
      significantly shorter than that in RL group ( days: 12.50+/-8.83 vs. 17.10+/
      16.60, t = 9.037, P<0.001 ), but there was no significant difference in mortality
      between HES group and RL group [ 40.9% ( 18/44 ) vs. 60.0% ( 24/40 ), chi (2) =
      2.339, P = 0.126 ]. CONCLUSIONS: Both RL and hydroxyethyl starch fluid
      resuscitation did not affect the PT of the patients. The use of hydroxyethyl
      starch probably inhibits excessive activation of the exogenous coagulation and
      hyper-coagulation in the early stage of sepsis, and inhibits activation of
      protein C as well.

PMID- 25591434
TI  - [Assessment of fluid volume in critically ill patients with extravascular lung
      water index].
AB  - OBJECTIVE: To examine the effect of rapid infusion test guided by extravascular
      lung water index ( EVLWI ) on hemodynamics in critically ill patients at
      different states in order to guide volume resuscitation. METHODS: A prospective
      observation was conducted. Forty critically ill patients admitted to Department
      of Critical Care Medicine of Tianjin Third Central Hospital from June 2012 to
      April 2014 were enrolled. Based on the levels of EVLWI and pulmonary vascular
      permeability index ( PVPI ) and the cardiac function, the patients were divided
      into four groups: septic patients with normal EVLWI and PVPI ( n = 17 ), septic
      patients with increased EVLWI and PVPI ( n = 3 ), septic patients with increased
      EVLWI and normal PVPI ( n = 4 ), and coronary heart disease and heart failure
      patients with normal EVLWI and PVPI ( n = 16 ). The rapid infusion test was
      conducted in all patients using lactated Ringer solution 250 mL, followed by
      infusion of crystalloid with rate of 150 mL/h. The conditions of mechanical
      ventilation and vasoactive drugs were not changed during study. The changes in
      EVLWI, intrathoracic blood volume index ( ITBVI ), and cardiac index ( CI )
      before capacity load, at immediate capacity load, and 15, 45, 105 minutes after
      load were determined by pulse indicator continuous cardiac output ( PiCCO ). On
      the base of volume status before and after the liquid infusion, the standard for
      the changes were: stroke volume ( SV ) increased by 12%-15%, central venous
      pressure ( CVP ) greater >= 2 mmHg ( 1 mmHg = 0.133 kPa ), CI>15%, and ITBVI
      change greater than 10%. RESULTS: There were no statistically significant
      differences in the observed indicators at the each time point before and after
      rapid infusion test among the four groups ( all P>0.05 ). In septic patients with
      normal EVLWI and PVPI group, ITBVI was slightly increased by 5.4%-9.7% from 15
      minutes to 45 minutes after rapid infusion test. In coronary heart disease and
      heart failure patients with normal EVLWI and PVPI group, the EVLWI was increased
      by 11.9%, 5.9%, and 14.7% respectirely at 15, 45, and 105 minutes, ITBVI was
      slightly increased by 6.4% at 45 minutes, CI was increased by 29.5% immediately
      after rapid infusion. In septic patients with increased EVLWI and PVPI group, CVP
      was increased by 8 mmHg immediately, EVLWI was increased significantly by 15.8%
      at 45 minutes, ITBVI was slightly decreased by 10.0% at 45 minutes, CI was
      increased by 24.7% immediately, and increased by 17.0% at 105 minutes, and PVPI
      was increased by 15.6%-28.1% at 15-105 minutes after rapid infusion. In septic
      patients with increased EVLWI and normal PVPI group, CVP was increased by 1.5
      mmHg at 15 minutes, EVLWI was increased immediately, which was increased by
      17.4%, 24.0%, and 31.4% respectively at 15, 45, and 105 minutes, ITBVI was
      increased by 13.9% at 15 minutes, CI was increased by 16.1% at 15 minutes after
      rapid fluid infusion. CONCLUSIONS: Rapid fluid replacement in critically ill
      patients with crystalloid, regardless of whether the EVLWI was normal or
      increased, the short-term response was affected by the volume and cardiac
      function of patients. Different status of patients showed different volume effect
      curve: no significant changes in hemodynamic parameters were found in patients
      with normal EVLWI and volume parameters. In patients with potential cardiac
      dysfunction, CI and EVLWI increased significantly; regardless of PVPI increased
      or normal, EVLWI and CI were increased in patients with elevated EVLWI; two
      different changes could be found in the two types of pulmonary edema while ITBVI
      was increased.

PMID- 25591435
TI  - [Retrospective analysis of the value of arterial blood lactate level and its
      clearance rate on the prognosis of septic shock patients].
AB  - OBJECTIVE: To explore the prognostic value of arterial blood lactate ( Lac )
      levels and lactate clearance rate ( LCR ) in the patients with septic shock.
      METHODS: A retrospective study was conducted. Clinical data of 94 septic patients
      admitted in the Department of Critical Care Medicine in Subei People's Hospital
      from January 2011 to June 2014 were analyzed. The arterial blood Lac levels at
      the moment of diagnosis of septic shock ( incipient value, 0 hour ) and early
      stage after treatment ( 3, 6 and 24 hours ) were reviewed, and individual LCR was
      calculated at 3, 6, 24 hours for each patient. According to the outcome in
      intensive care unit ( ICU ), patients were divided into survival group ( n = 48 )
      and death group ( n = 46 ). The Lac and LCR at different time points in two
      groups were analyzed, and the relationships between them and outcome were
      analyzed. The receiver-operating characteristic ( ROC ) curve was plotted to
      assess the value of Lac and LCR at different time points for predicting the
      outcome. RESULTS: Lac level after treatment in survival group was significantly
      lower than incipient value, but there was no obvious change in death group.
      Compared with death group, early Lac levels ( mmol/L ) in survival group were
      significantly reduced ( 0 hour: 3.80+/-2.14 vs. 5.75+/-3.21, 3 hours: 2.05+/-1.04
      vs. 5.03+/-2.53, 6 hours: 1.80+/-0.77 vs. 4.40+/-2.02, 24 hours: 1.35+/-0.43 vs.
      4.90+/-2.72, P<0.05 or P<0.01 ), the LCR was significantly increased [ 3 hours:
      50.00 ( 72.35 )% vs. 13.51 ( 20.67 )%, 6 hours: 41.43 ( 58.42 )% vs. 22.00 (
      22.31 )%, 24 hours: 58.73 ( 29.94 )% vs. 18.92 ( 47.28 )%, P<0.05 or P<0.01 ].
      The Lac levels at all time points were positively correlated with the outcome,
      and 6-hour and 24-hour LCR were negatively correlated with the outcome. According
      to the incipient Lac level, patients were divided into low Lac group ( Lac<2
      mmol/L ), mild Lac group ( Lac 2-3 mmol/L ) and high Lac group ( Lac >= 4 mmol/L
      ). The mortality in low Lac group, mild Lac group, high Lac group was gradually
      increased [ 23.07% ( 6/26 ), 50.00% ( 8/16 ), 61.54% ( 32/52 ), chi(2) = 10.270,
      P = 0.006 ]. ROC curves demonstrated that the area under ROC curve ( AUC ) of 24
      hour Lac was the largest, 0.944, and it was more sensitive and specific in the
      prognosis evaluation ( 100% and 78.3%, respectively ). According to the cut-off
      value of 24-hour Lac as 2.35 mmol/L, patients were divided into high Lac and low
      Lac groups, and mortality rate in high Lac group was significantly higher than
      that in low Lac group [ 100.0% ( 36/36 ) vs. 17.24% ( 10/58 ), chi(2) = 30.441,P
      = 0.000 ]. The AUC of 24-hour LCR was the largest, 0.865, and it was more
      sensitive and specific for the prognosis evaluation ( 83.3% and 91.3%,
      respectively ). According to the cut-off value of 24-hour LCR as 36.8%, patients
      were divided into high LCR group and low LCR group, and mortality rate in low LCR
      group was significantly higher than that in high LCR group [ 84.00% ( 42/50 ) vs.
      9.09% ( 4/44 ), chi(2) = 26.278, P = 0.000 ]. CONCLUSIONS: Early high Lac in
      patients with septic shock prompts a poor prognosis, and 24-hour Lac levels and
      LCR are indicators of assessment of clinical therapeutic effect and prognosis of
      patients with septic shock.

PMID- 25591436
TI  - [Early predictive value of hemodynamic parameters during fluid resuscitation in
      patients with sepsis shock].
AB  - OBJECTIVE: To investigate the short term predictive value of hemodynamic
      parameters during fluid resuscitation in patients with septic shock. METHODS:
      Data of 76 patients with septic shock admitted to Department of Critical Care
      Medicine of Beijing Shijitan Hospital from January 2013 to October 2014 were
      retrospectively analyzed. The hemodynamic parameters were monitored by pulse
      indicator continuous cardiac output ( PiCCO ), including mean arterial pressure (
      MAP ), stroke volume index ( SVI ), cardiac index ( CI ), global ejection
      fraction ( GEF ), global end diastolic volume index ( GEDVI ), intrathoracic
      blood volume index ( ITBVI ), extravascular lung water index ( EVLWI ), systemic
      vascular resistance index ( SVRI ), and pulmonary vascular permeability index (
      PVPI ). They were recorded before and 6 hours after fluid resuscitation.
      According to the prognosis on the 7th day, the patients were divided into
      survival group ( n = 42 ) and death group ( n = 34 ). The PiCCO records between
      two groups were compared and a receiver operating characteristic ( ROC ) curve
      for predicting the outcome was plotted to find the cut-off point value for each
      PiCCO record before and 6 hours after fluid resuscitation.The factors for
      predicting 7-day prognosis of patients with septic shock were analyzed by
      multivariate logistic regression analysis. RESULTS: (1) Compared with those
      before fluid resuscitation, EVLWI and PVPI were significantly decreased at 6
      hours after fluid resuscitation in the survival group [ EVLWI ( mL/kg ): 7.33+/
      1.72 vs. 9.07+/-2.81, PVPI: 1.39+/-0.34 vs. 1.74+/-0.50, both P<0.01 ] but they
      were significantly increased in the death group [ EVLWI ( mL/kg ): 12.62+/-3.58
      vs. 8.97+/-2.74, PVPI: 2.36+/-0.81 vs. 1.73+/-0.60, both P<0.01 ], and MAP in the
      death group decreased after fluid resuscitation [ MAP ( mmHg, 1 mmHg = 0.133 kPa
      ): 70.53+/-12.12 vs. 77.06+/-13.48, P<0.01 ]. (2)ROC curve showed that the area
      under ROC curve ( AUC ) of EVLWI at 6 hours after fluid resuscitation was 0.914,
      cut-off value was 9.50 mL/kg, the sensitivity was 82.4% and the specificity was
      88.1%. The AUC of PVPI was 0.890, when cut-off value was 1.75, the sensitivity
      was 73.5%, and the specificity was 92.9%. (3) It was shown by multivariate
      logistic regression analysis that only EVLWI at 6 hours after fluid resuscitation
      was an independent predictor for 7-day prognosis of septic patient [ odds ratio (
      OR ) = 0.546, 95% confidence interval ( 95%CI ) = 0.852-0.976, P = 0.006 ].
      CONCLUSIONS: PiCCO monitoring indicators such as EVLWI, PVPI and MAP have certain
      prognostic value for septic patients, but only EVLWI at 6 hours after fluid
      resuscitation is an independent prognostic factor for short term prognosis.

PMID- 25591437
TI  - [Value of detection of pentraxins 3 value combined with measurement of vascular
      lung water index in prognosis of patients with sepsis].
AB  - OBJECTIVE: To evaluate prognostic value of pentraxin3 ( PTX3 ) content combining
      with extravascular lung water index ( EVLWI ) in patients with sepsis. METHODS: A
      retrospective analysis of complete clinical data of septic patients admitted to
      Department of Critical Care Medicine of the First Affiliated Hospital of
      Zhengzhou University from February 2013 to February 2014 was conducted. These
      patients were divided into two groups, survival group and death group, according
      to the outcome on the 28th day. Pulse index continuous cardiac output ( PiCCO )
      was used to record the levels of EVLWI on the 1st, 2nd and 3rd day of intensive
      care unit ( ICU ) admission. The plasma level of PTX3 was measured simultaneously
      by enzyme-linked immunosorbent assay ( ELISA ). At the same time, acute
      physiology and chronic health evaluation II ( APACHEII) score and sequential
      organ failure assessment ( SOFA ) were calculated. Correlation analysis between
      plasma PTX3 and EVLWI values was performed, receiver operating characteristic
      curve ( ROC ) was drawn, and the prognostic value of each parameter was assessed
      finally. RESULTS: A total of 74 septic patients were enrolled, with 41 cases in
      the survival group and 33 cases in the non-survival group. Blood lactate,
      APACHEII, SOFA scores in the non-survival group were significantly higher than
      those of the survival group at ICU admission, and the length of ICU stay was
      significantly shorter than that of the survival group, while differences of the
      other clinical characteristics between two groups were not statistically
      significant. The plasma PTX3 level gradually declined with time in both groups,
      and plasma PTX3 at 1, 2, 3 days after ICU admission in non-survival group were
      significantly higher than those in survival group [ PTX3 ( MUg/L ) at 1 day:
      46.3+/-10.5 vs. 19.4+/-6.5, t = -13.486, P = 0.000; 2 days: 34.8+/-10.7 vs.
      17.7+/-8.4, t = -8.284, P = 0.000; 3 days: 23.9+/-11.2 vs. 15.6+/-7.9, t = 
      5.036, P = 0.000 ]. EVLWI gradually declined in survival group, but increased in
      death group. EVLWI at 1, 2, 3 days after ICU admission in non-survival group were
      significantly higher than those in survival group [ EVLWI ( mL/kg ) at 1 day:
      12.12+/-4.31 vs. 10.02+/-2.87, t = -2.502, P = 0.023; 2 days: 13.67+/-4.95 vs.
      9.08+/-2.89, t = -5.188, P = 0.000; 3 days: 14.51+/-5.06 vs. 8.09+/-2.50, t = 
      7.126, P = 0.000 ]. PTX3 at 1, 2, 3 days after ICU admission showed a significant
      positive correlation with EVLWI ( r1 = 0.747, r2 = 0.719, r3 = 0.705, all P =
      0.000 ). ROC curve analysis showed that the area under the ROC ( AUC ) of PTX3 at
      1 day was 0.845+/-0.045, at the cut-off point of 23.0 MUg/L, PTX3 showed a
      sensitivity of 84.8%, a specificity of 74.1%, a negative predictive value of
      85.81%, and a positive predictive value of 72.42%. AUC of EVLWI at 3 days was
      0.838+/-0.048, at the cut-off point of 10.5 mL/kg, EVLWI showed a sensitivity of
      83.9%, a specificity of 82.9%, a negative predictive value of 86.45%, and a
      positive predictive value of 79.79%. Their sensitivities and specificities were
      found to be better than APACHEII, SOFA score. AUC of PTX3 combined with EVLWI at
      1 day was 0.886+/-0.038. On the 1st day after ICU admission, with combination of
      the two indicators, cut-off point was found to be 0.312, a sensitivity of 86.8%,
      a specificity of 85.4%, a negative predictive value of 88.93%, and a positive
      predictive value of 82.72%. On the 3rd day after ICU admission, AUC of PTX3
      combined with EVLWI was 0.856+/-0.046, and showed a cut-off of 0.471 for the
      prognosis of sepsis, a sensitivity of 85.8%, a specificity of 85.4%, a negative
      predictive value of 87.97%, and a positive predictive value of 82.50%. Compared
      with other single index, a combination of above mentioned two indexes showed a
      better sensitivity and specificity. CONCLUSIONS: PTX3 can serve as a novel
      prognostic indicator at early stage in septic patients. Combined with EVLWI, it
      shows important value in predicting prognosis of septic patients, and it also
      provides guidance in treatment of high-risk patients.

PMID- 25591438
TI  - [Effect of compound hypertonic saline solution on septic rats].
AB  - OBJECTIVE: To study the effect of compound hypertonic saline solution ( HSD ) on
      sepsis. METHODS: 133 male Wistar rats were divided into four groups, sham
      operation group ( n = 15 ), cecal ligation and puncture ( CLP ) group ( n = 45 ),
      CLP plus normal saline ( NS ) group ( n = 45 ), and CLP plus HSD group ( n = 28
      ). A rat model of sepsis was reproduced by CLP, and the rats in sham operation
      group received celiotomy without ligation and puncture. All rats in four groups
      received subcutaneous injection of 30 mL/kg 0.9% sodium chloride after
      laparotomy. The rats in CLP plus NS group and CLP plus HSD group received
      infusion of 5 mL/kg 0.9% sodium chloride or 7.5% sodium chloride/6% dextran post
      CLP via jugular vein for 3 hours, with the infusion rate of 0.4 mL*kg(-1)*min(
      1). The survival rate of each group was observed 9 hours and 18 hours after
      laparotomy. Mean arterial pressure ( MAP ) at 0, 9, 18 hours were monitored.
      Blood specimens were collected from all rats 0, 9 and 18 hours after laparotomy,
      respectively, for measurement of the plasma levels of tumor necrosis factor-alpha
      ( TNF-alpha), interleukin-1beta ( IL-1beta ), and procalcitonin ( PCT ). The rats
      were all sacrificed, and their lung tissues were harvested for the neutrophil
      count in bronchoalveolar lavage fluid ( BALF ), myeloperoxidase ( MPO ) activity
      in lung tissue, wet/dry weight ratio ( W/D ) of lung, and pathological changes in
      lung tissue. RESULTS: There was no death in the sham operation group. The
      survival rates at 9 hours and 18 hours were 62.2% and 31.1% in the CLP group,
      57.8% and 35.6% in the CLP plus NS group, 85.7% and 64.3% in the CLP plus HSD
      group, and they were all significantly higher compared with those of the CLP
      group and the CLP plus NS group ( P<0.05 or P<0.01 ). MAP levels in the CLP group
      and the CLP plus NS group were significantly lower than those in sham operation
      group, and the plasma levels of TNF-alpha, IL-1beta and PCT were significantly
      higher compared with those of sham operation group, while there was no difference
      between CLP group and the CLP plus NS group. MAP and the plasma levels of TNF
      alpha, IL-1beta and PCT in the CLP plus HSD group were significantly improved
      compared with those of the CLP plus NS group at 9 hours and 18 hours [ MAP (
      mmHg, 1 mmHg = 0.133 kPa ) at 9 hours: 102+/-5 vs. 94+/-6, 18 hours: 90+/-2 vs.
      72+/-3; TNF-alpha ( ng/L ) at 9 hours: 284.19+/-57.18 vs. 329.67+/-45.79, 18
      hours: 263.46+/-42.58 vs. 349.68+/-52.40; IL-1beta ( ng/L ) at 9 hours: 219.28+/
      39.21 vs. 263.47+/-32.36, 18 hours: 195.98+/-39.06 vs. 250.10+/-41.57; PCT (
      MUg/L ) at 9 hours: 2.32+/-0.37 vs. 4.52+/-0.75, 18 hours: 2.89+/-0.62 vs. 5.02+/
      0.84; P<0.05 or P<0.01 ]. The ratio of neutrophils in BALF, MPO activity and lung
      W/D at 18 hours in the CLP group and the CLP plus NS group were significantly
      higher than those of the sham operation group, while they were all significantly
      lower in the CLP plus HSD group than those of the CLP group and the CLP plus NS
      group [ ratio of neutrophils in BALF: 0.094+/-0.019 vs. 0.148+/-0.062, 0.151+/
      0.055; MPO ( U/g ): 1.19+/-0.45 vs. 2.31+/-0.79, 2.64+/-0.69; lung W/D ratio:
      4.02+/-0.63 vs. 5.14+/-0.59, 5.12+/-0.83, all P<0.05 ]. Under light microscope,
      no pathobiological changes were found in sham operation group. The lung tissues
      in the CLP group and the CLP plus NS group showed congestion, edema, infiltrating
      inflammatory changes, while the inflammatory changes in the lung tissue in the
      CLP plus HSD group were significantly alleviated. CONCLUSIONS: HSD can obviously
      ameliorate the circulatory failure in septic rats, alleviate immune disturbance
      and acute lung injury, and improve the survival rate of rats with sepsis.

PMID- 25591439
TI  - [Dynamic effects of adjunct peritoneal resuscitation on the early intestinal
      injury of rats after hemorrhagic shock].
AB  - OBJECTIVE: To investigate the dynamic effects of adjunct peritoneal resuscitation
      ( APR ) on the early intestinal injury of rats with hemorrhagic shock, and
      explore its possible mechanisms. METHODS: According to random number table, 96
      male Wistar rats were assigned randomly into control group, shock group, Ringer
      solution APR group and dialysate APR group. Each group was further divided into
      three time points, namely 1, 2, and 6 hours after resuscitation, with 8 rats for
      each time point. The model of hemorrhagic shock was reproduced. The rats in the
      shock group received shed blood plus twice amount of normal saline as
      conventional intravenous resuscitation ( CIR ). Besides CIR, at the beginning of
      resuscitation, those rats in Ringer solution APR and dialysate APR groups were
      given 100 mL/kg of Ringer solution or 2.5% glucose-based peritoneal dialysis
      solution intravenously, respectively. The rats in four groups were sacrificed at
      1, 2 and 6 hours after resuscitation, respectively. Plasma activity of diamine
      oxidase ( DAO ) was detected by ultraviolet spectrophotometry colorimetry.
      Intestinal pathological changes were observed under light microscope, and the
      grading of the intestinal mucosal damage ( GIMD ) score was estimated. The
      expressions of nuclear factor-KappaB ( NF-KappaB ) and heat shock protein 70 (
      HSP70 ) mRNA in the intestinal tissue were determined with reverse transcription
      polymerase chain reaction ( RT-PCR ), and the wet/dry weight ratios ( W/D ) of
      the remaining intestinal tissue were measured. RESULTS: Compared with the control
      group, plasma activity of DAO, GIMD score, expressions of NF-KappaB and HSP70
      mRNA and W/D ratios of intestinal tissue at 1 hour after resuscitation were
      increased significantly in the shock group. Except the expression of NF-KappaB
      mRNA reached the peak level at 2 hours after resuscitation, all the other
      parameters increased with time. Compared with the shock group, plasma activity of
      DAO ( U/L: 8.78+/-0.76 vs. 13.30+/-1.37, 9.67+/-0.92 vs. 16.56+/-1.61, 10.53+/
      0.84 vs. 18.31+/-1.72,all P<0.05 ), GIMD score ( 1.36+/-0.31 vs. 3.51+/-0.66,
      2.28+/-0.40 vs. 4.02+/-0.76, 2.47+/-0.38 vs. 4.76+/-0.77, all P<0.05 ), the
      expressions of NF-KappaB mRNA in the intestine tissue ( gray value: 0.658+/-0.062
      vs. 0.765+/-0.067, 0.945+/-0.077 vs. 1.158+/-0.096, 0.761+/-0.062 vs. 0.912+/
      0.082, all P<0.05 ), and W/D ratios ( 3.91+/-0.26 vs. 4.34+/-0.33, 3.96+/-0.32
      vs. 4.51+/-0.40, 4.37+/-0.33 vs. 4.99+/-0.43, all P<0.05 ) at 1, 2, 6 hours after
      resuscitation in the dialysate APR group were decreased significantly, but the
      expressions of HSP70 mRNA were increased significantly ( gray value: 0.717+/
      0.054 vs. 0.635+/-0.056, 0.853+/-0.068 vs. 0.745+/-0.071, 1.258+/-0.111 vs.
      1.108+/-0.105, all P<0.05 ). The activity of DAO and GMID score at 1 hour after
      resuscitation in the Ringer solution APR group were decreased significantly
      compared with the shock group, while the differences of the other parameters
      between the Ringer solution APR group and shock group showed no statistical
      significance. CONCLUSIONS: APR with 2.5% glucose-based peritoneal dialysis
      solution can significantly mitigate the early intestinal injury secondary to
      hemorrhagic shock, and the mechanism may be associated with enhancement of the
      expressions of HSP70 mRNA and inhibition of the expressions of NF-KappaB mRNA.

PMID- 25591440
TI  - [Effect of early bundle treatment on the prognosis of patients in septic shock].

PMID- 25591441
TI  - [Development and application of multifunctional blood treatment vehicle].

PMID- 25591442
TI  - [Advances in functional hemodynamic monitoring].

PMID- 25591443
TI  - [Oxygen metabolism monitoring in septic shock].

PMID- 25591444
TI  - [Advance in application of bioreactance in the evaluation of fluid responsiveness
      in critically ill patients].

PMID- 25591446
TI  - Students' beliefs and behaviour regarding low-calorie beverages, sweets or
      snacks: are they affected by lessons on healthy food and by changes to school
      vending machines?
AB  - OBJECTIVE: To study the effects of school lessons about healthy food on
      adolescents' self-reported beliefs and behaviour regarding the purchase and
      consumption of soft drinks, water and extra foods, including sweets and snacks.
      The lessons were combined with the introduction of lower-calorie foods, food
      labelling and price reductions in school vending machines. DESIGN: A cluster
      randomized controlled design was used to allocate schools to an experimental
      group (i.e. lessons and changes to school vending machines) and a control group
      (i.e. 'care as usual'). Questionnaires were used pre-test and post-test to assess
      students' self-reported purchase of extra products and their knowledge and
      beliefs regarding the consumption of low-calorie products. SETTING: Secondary
      schools in the Netherlands. SUBJECTS: Twelve schools participated in the
      experimental group (303 students) and fourteen in the control group (311
      students). The students' mean age was 13.6 years, 71.5% were of native Dutch
      origin and mean BMI was 18.9 kg/m(2). RESULTS: At post-test, the experimental
      group knew significantly more about healthy food than the control group. Fewer
      students in the experimental group (43%) than in the control group (56%) reported
      bringing soft drinks from home. There was no significant effect on attitude,
      social norm, perceived behavioural control and intention regarding the
      consumption of low-calorie extra products. CONCLUSIONS: The intervention had
      limited effects on students' knowledge and self-reported behaviour, and no effect
      on their beliefs regarding low-calorie beverages, sweets or snacks. We recommend
      a combined educational and environmental intervention of longer duration and
      engaging parents. More research into the effects of such interventions is needed.

PMID- 25591445
TI  - Association of cartilage degeneration with four year weight gain--3T MRI data
      from the Osteoarthritis Initiative.
AB  - OBJECTIVE: To determine the effect of weight gain on progression of early knee
      morphologic abnormalities using magnetic resonance imaging (MRI) in a
      longitudinal study over 48 months. DESIGN: We studied the right knee of 100
      subjects from the Osteoarthritis Initiative (OAI), selecting subjects aged >= 45
      with osteoarthritis (OA) risk factors who demonstrated weight gain (minimum 5%
      increase in body mass index, BMI, n = 50) or no change in weight (BMI change <
      2%, n = 50), frequency matched for age, gender, and baseline BMI. Baseline and 48
      month knee MRI studies were scored for lesions using a modified whole organ MRI
      score (WORMS). Logistic regression models were used to compare the differences
      between the two groups. RESULTS: The odds of worsening maximum cartilage (11.3,
      95%, CI 3.5-51.4) and meniscal WORMS (4.5, 95% CI 1.4-17.3) were significantly
      greater in the weight gain group compared to the no change group, in addition to
      the odds of worsening cartilage defects at the patella and average meniscal WORMS
      (P < 0.05). Odds of worsening average bone marrow edema pattern (BMEP) were
      significantly greater for the weight gain group compared to the no change cohort
      (P < 0.05). CONCLUSION: Our study demonstrated that weight gain is strongly
      associated with increased progression of cartilage degeneration in middle-aged
      individuals with risk factors for OA.

PMID- 25591447
TI  - Carbon nanotubes activate macrophages into a M1/M2 mixed status: recruiting naive
      macrophages and supporting angiogenesis.
AB  - The potential of carbon nanotubes (CNTs) in medical applications has been
      attracting constant research interest as well as raising concerns related to
      toxicity. The immune system serves as the first line of defense against invasion.
      In this work, interactions of oxidized multiwalled carbon nanotubes (MWCNT) with
      macrophages were investigated to unravel the activation profile of macrophages,
      using cytokine array, ELISA assay, transwell assay, confocal microscopy, and
      reactive oxygen species examination. Results show that MWCNT initiate
      phagocytosis of macrophages and upregulate CD14, CD11b, TLR-4/MD2, and CD206,
      which does not alter the MHCII expression of the macrophages. The macrophages
      engulfing MWCNT (MWCNT-RAW) secrete a large amount of MIP-1alpha and MIP-2 to
      recruit naive macrophages and produce angiogenesis-related cytokines MMP-9 and
      VEGF, while inducing much lower levels of proinflammatory cytokines than those
      activated by LPS. In conclusion, MWCNT activate macrophages into a M1/M2 mixed
      status, which allows the cells to recruit naive macrophages and support
      angiogenesis. 

PMID- 25591448
TI  - Proteomics reveals the importance of the dynamic redistribution of the
      subcellular location of proteins in breast cancer cells.
AB  - At the molecular level, living cells are enormously complicated complex adaptive
      systems in which intertwined genomic, transcriptomic, proteomic and metabolic
      networks all play a crucial role. At the same time, cells are spatially
      heterogeneous systems in which subcellular compartmentalization of different
      functions is ubiquitous and requires efficient cross-compartmental communication.
      Dynamic redistribution of multitudinous proteins to different subcellular
      locations in response to cellular functional state is increasingly recognized as
      a crucial characteristic of cellular function that seems to be at least as
      important as overall changes in protein abundance. Characterization of the
      subcellular spatial dynamics of protein distribution is a major challenge for
      proteomics and recent results with MCF7 breast cancer cells suggest that this may
      be of particular importance for cancer cells. 

PMID- 25591449
TI  - PathPPI: an integrated dataset of human pathways and protein-protein
      interactions.
AB  - Integration of pathway and protein-protein interaction (PPI) data can provide
      more information that could lead to new biological insights. PPIs are usually
      represented by a simple binary model, whereas pathways are represented by more
      complicated models. We developed a series of rules for transforming protein
      interactions from pathway to binary model, and the protein interactions from
      seven pathway databases, including PID, BioCarta, Reactome, NetPath, INOH, SPIKE
      and KEGG, were transformed based on these rules. These pathway-derived binary
      protein interactions were integrated with PPIs from other five PPI databases
      including HPRD, IntAct, BioGRID, MINT and DIP, to develop integrated dataset
      (named PathPPI). More detailed interaction type and modification information on
      protein interactions can be preserved in PathPPI than other existing datasets.
      Comparison analysis results indicate that most of the interaction overlaps values
      (O AB) among these pathway databases were less than 5%, and these databases must
      be used conjunctively. The PathPPI data was provided at
      http://proteomeview.hupo.org.cn/PathPPI/PathPPI.html. 

PMID- 25591450
TI  - An inverse approach to identifying the in vivo material parameters of female
      pelvic floor muscles using MRI data.

PMID- 25591451
TI  - Kindler syndrome protein Kindlin-1 is mainly expressed in adult tissues
      originating from ectoderm/endoderm.
AB  - Mutations of integrin-interacting protein Kindlin-1 cause Kindler syndrome and
      deregulation of Kindlin-1 is implicated in human cancers. The Kindlin-1-related
      diseases are confined in limited tissue types. However, Kindlin-1 tissue
      distribution and the dogma that governs Kindlin-1 expression in normal human body
      are elusive. This study examined Kindlin-1 expression in normal human adult
      organs, human and mouse embryonic organs by immunohistochemical analyses. We
      identified a general principle that the level of Kindlin-1 expression in tissues
      is tightly correlated with the corresponding germ layers from which these tissues
      originate. We compared the expression of Kindlin-1 with Kindlin-2 and found that
      Kindlin-1 is highly expressed in epithelial tissues derived from ectoderm and
      endoderm, whereas Kindlin-2 is mainly expressed in mesoderm-derived tissues.
      Likewise, Kindlin-1 was also found highly expressed in endoderm/ectoderm-derived
      tissues in human and mouse embryos. Our findings indicate that Kindlin-1 may play
      an importance role in the development of endoderm/ectoderm related tissues. 

PMID- 25591452
TI  - Virus genomes and virus-host interactions in aquaculture animals.
AB  - Over the last 30 years, aquaculture has become the fastest growing form of
      agriculture production in the world, but its development has been hampered by a
      diverse range of pathogenic viruses. During the last decade, a large number of
      viruses from aquatic animals have been identified, and more than 100 viral
      genomes have been sequenced and genetically characterized. These advances are
      leading to better understanding about antiviral mechanisms and the types of
      interaction occurring between aquatic viruses and their hosts. Here, based on our
      research experience of more than 20 years, we review the wealth of genetic and
      genomic information from studies on a diverse range of aquatic viruses, including
      iridoviruses, herpesviruses, reoviruses, and rhabdoviruses, and outline some
      major advances in our understanding of virus-host interactions in animals used in
      aquaculture. 

PMID- 25591453
TI  - A surprising role for the Sch9 protein kinase in chromosome segregation in
      Candida albicans.
AB  - The AGC kinase Sch9 regulates filamentation in Candida albicans. Here, we show
      that Sch9 binding is most enriched at the centromeres in C. albicans, but not in
      Saccharomyces cerevisiae. Deletion of CaSch9 leads to a 150- to 750-fold increase
      in chromosome loss. Thus, we report a previously unknown role of Sch9 in
      chromosome segregation. 

PMID- 25591456
TI  - Ion counting in supercapacitor electrodes using NMR spectroscopy.
AB  - (19)F NMR spectroscopy has been used to study the local environments of anions in
      supercapacitor electrodes and to quantify changes in the populations of adsorbed
      species during charging. In the absence of an applied potential, anionic species
      adsorbed within carbon micropores (in-pore) are distinguished from those in large
      mesopores and spaces between particles (ex-pore) by a characteristic nucleus
      independent chemical shift (NICS). Adsorption experiments and two-dimensional
      exchange experiments confirm that anions are in dynamic equilibrium between the
      in- and ex-pore environments with an exchange rate in the order of tens of Hz.
      (19)F in situ NMR spectra recorded at different charge states reveal changes in
      the intensity and NICS of the in-pore resonances, which are interpreted in term
      of changes in the population and local environments of the adsorbed anions that
      arise due to the charge-storage process. A comparison of the results obtained for
      a range of electrolytes reveals that several factors influence the charging
      mechanism. For a tetraethylammonium tetrafluoroborate electrolyte, positive
      polarisation of the electrode is found to proceed by anion adsorption at a low
      concentration, whereas increased ion exchange plays a more important role for a
      high concentration electrolyte. In contrast, negative polarization of the
      electrode proceeds by cation adsorption for both concentrations. For a
      tetrabutylammonium tetrafluoroborate electrolyte, anion expulsion is observed in
      the negative charging regime; this is attributed to the reduced mobility and/or
      access of the larger cations inside the pores, which forces the expulsion of
      anions in order to build up ionic charge. Significant anion expulsion is also
      observed in the negative charging regime for alkali metal
      bis(trifluoromethane)sulfonimide electrolytes, suggesting that more subtle
      factors also affect the charging mechanism. 

PMID- 25591455
TI  - Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced
      nephropathy and cardiomyopathy via inhibition of oxidative stress and
      inflammatory response.
AB  - BACKGROUND: Abroma augusta L. (Malvaceae) leaf is traditionally used to treat
      diabetes in India and Southern Asia. Therefore, current study was performed to
      evaluate the protective effect of defatted methanol extract of A. augusta leaves
      (AA) against type 2 diabetes mellitus (T2DM) and its associated nephropathy and
      cardiomyopathy in experimental rats. METHODS: Antidiabetic activity of AA
      extracts (100 and 200 mg/kg, p.o.) was measured in streptozotocin-nicotinamide
      induced type 2 diabetic (T2D) rat. Fasting blood glucose level (at specific
      interval) and serum biochemical markers (after sacrifice) were measured. Redox
      status, transcription levels of signal proteins (NF-kappaB and PKCs),
      mitochondria dependent apoptotic pathway (Bad, Bcl-2, caspase cascade) and
      histological studies were performed in kidneys and hearts of controls and AA
      treated diabetic rats. RESULTS: Phytochemical screening of extracts revealed the
      presence of taraxerol, flavonoids and phenolic compounds in the AA. T2D rats
      showed significantly (p < 0.01) elevated fasting blood glucose level. Alteration
      in serum lipid profile and release of membrane bound enzymes like lactate
      dehydrogenase and creatine kinase, which ensured the participation of
      hyperlipidemia and cell membrane disintegration in diabetic pathophysiology. T2DM
      caused alteration in the serum biochemical markers related to diabetic
      complications. T2DM altered the redox status, decreased the intracellular NAD and
      ATP concentrations in renal and myocardial tissues of experimental rats.
      Investigating the molecular mechanism, activation PKC isoforms was observed in
      the selected tissues. T2D rats also exhibited an up-regulation of NF-kappaB and
      increase in the concentrations of pro-inflammatory cytokines (IL-1beta, IL-6 and
      TNF-alpha) in the renal and cardiac tissues. The activation of mitochondria
      dependent apoptotic pathway was observed in renal and myocardial tissues of the
      T2D rats. However, Oral administration of AA at the doses of 100 and 200 mg/kg
      body weight per day could reduce hyperglycemia, hyperlipidemia, membrane
      disintegration, oxidative stress, vascular inflammation and prevented the
      activation of oxidative stress induced signaling cascades leading to cell death.
      Histological studies also supported the protective characteristics of AA.
      CONCLUSIONS: Results suggest that AA could offer prophylactic role against T2DM
      and its associated reno- and cardio- toxicity.

PMID- 25591457
TI  - Agreement of olecranon fractures before and after the exposure to four
      classification systems.
AB  - BACKGROUND: Although classification systems of olecranon fractures are important
      to help choose the best treatment and to predict prognosis, their degree of
      observer agreement is poorly investigated. The objective of this study was to
      investigate the intraobserver and interobserver reliability of currently used
      classification systems for olecranon fractures. Our hypothesis is that the Colton
      classification presents an acceptable agreement because it is simpler to use; on
      the other hand, considering the AO classification's complexity, we expect it to
      reach a lower level of agreement. METHODS: Radiographic images of elbow joint
      fractures were classified according to Colton, AO, Mayo, and Schatzker
      classification systems. The raters were 8 orthopedic surgeons split into 2 groups
      with 4 participants each, one with specialists in upper extremity surgery and the
      other with orthopedic surgeons without a specific focus on upper extremity
      surgery. This first procedure was the pretest training, aimed at calibrating
      participants' judgment. Image classification was conducted after all training was
      completed. After 30 days from the initial rating session, the test was conducted
      once again following the exact same procedures. RESULTS: The Colton
      classification has substantial intraobserver and interobserver agreement for
      specialists and nonspecialists. The Schatzker classification revealed a fair
      agreement for both specialists and nonspecialists. A fair concordance was also
      found for the Mayo classification. The AO classification demonstrated a moderate
      rate of agreement for specialists, whereas nonspecialists presented slight
      intraobserver agreement. CONCLUSION: No classification system is widely accepted
      because it can be affected by interobserver variability, which can raise
      questions about its use in a research as well as in a clinical context.

PMID- 25591454
TI  - Ethnic-specific associations of rare and low-frequency DNA sequence variants with
      asthma.
AB  - Common variants at many loci have been robustly associated with asthma but
      explain little of the overall genetic risk. Here we investigate the role of rare
      (<1%) and low-frequency (1-5%) variants using the Illumina HumanExome BeadChip
      array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case-parent
      trios representing European Americans, African Americans/African Caribbeans and
      Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene
      that is associated with asthma in the Latino sample (P=4.31 * 10(-6); OR=1.25;
      MAF=1.21%) and two genes harbouring functional variants that are associated with
      asthma in a gene-based analysis: GSDMB at the 17q12-21 asthma locus in the Latino
      and combined samples (P=7.81 * 10(-8) and 4.09 * 10(-8), respectively) and MTHFR
      in the African ancestry sample (P=1.72 * 10(-6)). Our results suggest that
      associations with rare and low-frequency variants are ethnic specific and not
      likely to explain a significant proportion of the 'missing heritability' of
      asthma. 

PMID- 25591459
TI  - Scapulohumeral rhythm in shoulders with reverse shoulder arthroplasty.
AB  - BACKGROUND: Little is known about kinematic function of reverse total shoulder
      arthroplasty (RTSA). Scapulohumeral rhythm (SHR) is a common metric for assessing
      muscle function and shoulder joint motion. The purpose of this study was to
      compare SHR in shoulders with RTSA to normal shoulders. METHODS: Twenty-eight
      subjects, more than 12 months after unilateral RTSA, were recruited for an
      Institutional Review Board-approved study. Subjects performed arm abduction in
      the coronal plane with and without a 1.4-kg hand-held weight. Three-dimensional
      model-image registration techniques were used to measure orientation and position
      for the humerus and scapula from fluoroscopic images. Analysis of variance and
      Tukey tests were used to assess groupwise and pairwise differences. RESULTS: SHR
      in RTSA shoulders (1.3:1) was significantly lower than in normal shoulders (3:1).
      Below 30 degrees  abduction, RTSA and normal shoulders show a wide range of SHR
      (1.3:1 to 17:1). Above 30 degrees  abduction, SHR in RTSA shoulders was 1.3:1 for
      unweighted abduction and 1.3:1 for weighted abduction. Maximum RTSA shoulder
      abduction in weighted trials was lower than in unweighted trials. SHR variability
      in RTSA shoulders decreased with increasing arm elevation. CONCLUSION: RTSA
      shoulders show kinematics that are significantly different from normal shoulders.
      SHR in RTSA shoulders was significantly lower than in normal shoulders,
      indicating that RTSA shoulders use more scapulothoracic motion and less
      glenohumeral motion to elevate the arm. With these observations, it may be
      possible to improve rehabilitation protocols, with particular attention to the
      periscapular muscles, and implant design or placement to optimize functional
      outcomes in shoulders with RTSA.

PMID- 25591458
TI  - The influence of radiographic viewing perspective and demographics on the
      critical shoulder angle.
AB  - BACKGROUND: Accurate assessment of the critical shoulder angle (CSA) is important
      in clinical evaluation of degenerative rotator cuff tears. This study analyzed
      the influence of radiographic viewing perspective on the CSA, developed a
      classification system to identify malpositioned radiographs, and assessed the
      relationship between the CSA and demographic factors. METHODS: Glenoid height,
      width, and retroversion were measured on 3-dimensional computed tomography
      reconstructions of 68 cadaver scapulae. A digitally reconstructed radiograph was
      aligned perpendicular to the scapular plane, and retroversion was corrected to
      obtain a true anteroposterior (AP) view. In 10 scapulae, incremental
      anteversion/retroversion and flexion/extension views were generated. The CSA was
      measured, and a clinically applicable classification system was developed to
      detect views with >2 degrees  change in CSA vs. true AP view. RESULTS: The
      average CSA was 33 degrees  +/- 4 degrees . Intraobserver and interobserver
      reliability was high (intraclass correlation coefficient >= 0.81) but decreased
      with increasing viewing angle. Views beyond 5 degrees  anteversion, 8 degrees 
      retroversion, 15 degrees  flexion, and 26 degrees  extension resulted in >2
      degrees  deviation of the CSA compared with the true AP view. The classification
      system was capable of detecting aberrant viewing perspectives with sensitivity of
      95% and specificity of 53%. Correlations between glenoid size and CSA were small
      (R <= 0.3), and CSA did not vary by gender (P = .426) or side (P = .821).
      CONCLUSIONS: The CSA was most susceptible to malposition in
      anteversion/retroversion. Deviations as little as 5 degrees  in anteversion
      resulted in a CSA >2 degrees  from true AP view. A new classification system
      refines the ability to collect true AP radiographs of the scapula. The CSA was
      unaffected by demographic factors.

PMID- 25591460
TI  - Total elbow arthroplasty: outcomes after triceps-detaching and triceps-sparing
      approaches.
AB  - BACKGROUND: Total elbow arthroplasty (TEA) is associated with high complication
      rates compared with other large-joint arthroplasties. The frequency and type of
      complication may differ, depending on the surgical approach. A comparison of
      outcomes with triceps-off and triceps-on approaches was investigated. METHODS:
      Seventy-three patients underwent 83 primary TEAs between 2003 and 2012. Forty-six
      elbows had a triceps-off approach, and 37 had a triceps-on approach. Results were
      reviewed at a mean of 4.2 years. Cementing technique was graded according to
      Morrey's criteria, and clinical outcomes were assessed by means of the Mayo Elbow
      Performance Score. RESULTS: There was no statistically significant difference
      between the triceps-off and triceps-on groups with regard to the patient's age,
      gender, preoperative Mayo Elbow Performance Score or range of motion, or previous
      surgery on the affected elbow. Among patients who underwent a TEA for an
      inflammatory arthropathy, there was a significant difference in outcome between
      groups with regard to final flexion, extension, arc of motion, and pronation.
      Cementing technique in the triceps-off group was adequate in 70%. In the triceps
      on group, cementing technique was adequate in 92%. The complication rate in the
      triceps-off group was 32.6% and included 7 triceps ruptures. Three patients who
      had attempted repairs of the triceps rupture developed deep infections requiring
      multiple further surgeries. The complication rate in the triceps-on group was
      8.1%. CONCLUSION: A triceps-on approach in TEA results in consistently good
      clinical outcomes with no risk of triceps rupture, and the approach does not
      compromise the cement mantle. We believe that this approach will reduce
      complication rates in TEA.

PMID- 25591461
TI  - Predictors of length of stay after elective total shoulder arthroplasty in the
      United States.
AB  - BACKGROUND: Total shoulder arthroplasty (TSA) is an increasingly used treatment
      of glenohumeral arthritis and proximal humerus fractures. However, patient
      specific characteristics affecting length of hospital stay postoperatively have
      not been elucidated. METHODS: All patients undergoing primary unilateral TSA
      between 2005 and 2011 were isolated from the National Surgical Quality
      Improvement Program database. Patient demographics, medical comorbidities, and
      selected surgical variables were extracted, and length of stay was established as
      the primary end point of interest. Risk factors were expressed as odds ratios
      (ORs) with 95% confidence intervals by bivariate and multivariable analysis.
      RESULTS: A total of 2004 patients were identified; the average age was 68.8
      years, and 57% were women. Mean length of stay after TSA was 2.2 days (standard
      deviation, 1.7), and 91% of cases received hospital discharge in <3 days.
      Multivariable logistic regression analysis identified renal insufficiency (OR,
      11.35; P = .0002), increased age (OR, 2.13; P = .011), longer operative time (OR,
      1.94; P = .0041), and American Society of Anesthesiologists class >=3 (OR, 1.86;
      P = .0016) as the most significant risk factors for length of stay. Gender also
      influenced length of stay; women were more likely to stay >=4 days (OR, 0.44; P <
      .0001). CONCLUSIONS: Perioperative risk stratification and preoperative
      counseling are paramount for patients undergoing TSA, particularly for those
      individuals with cardiac and renal disease or of advancing age. These variables
      may effectively predict prolonged hospital stay after TSA.

PMID- 25591462
TI  - The effect of fracture comminution on the reliability and accuracy of radial head
      sizing.
AB  - BACKGROUND: Radial head implant sizing can be based on the maximum head diameter
      (D-MAX), the minimum head diameter (D-MIN), or the articular dish diameter (D
      DISH). The purpose of this study was to assess the reliability of the different
      radial head sizing techniques and to investigate the effect of radial head
      fracture comminution on measurement accuracy. METHODS: Ten observers measured 11
      cadaveric radial heads with 3 radial head features (D-MAX, D-MIN, and D-DISH
      diameter). Radial heads were then fractured into 2, 3, and 4 parts, and the
      measurements were repeated. Variability was assessed by intraclass correlation.
      The measurements were compared with the intact state to assess the effect of
      radial head fracture comminution on sizing accuracy. RESULTS: D-MAX and D-MIN
      measurements were the most reliable among all observers (intraclass correlation
      coefficients, 0.980, 0.973). The D-DISH measurement was less reliable (intraclass
      correlation coefficient, 0.643). Radial head comminution did not significantly
      affect the reliability of any measurement (P > .2). Fracture comminution,
      however, significantly affected measurement accuracy with D-MAX and D-DISH. With
      fracture comminution, D-MAX underestimated radial head diameter (-0.4 +/- 0.3 mm;
      P < .001), whereas D-DISH overestimated diameter (+0.5 +/- 0.4 mm; P < .001).
      Comminution did not significantly affect D-MIN (-0.1 +/- 0.3 mm; P = .13).
      DISCUSSION: The D-MAX and D-MIN measurements were more reliable than D-DISH for
      diameter sizing of intact and comminuted radial heads. Overall, increasing
      comminution did not significantly affect measurement reliability. However, the
      accuracy of the D-MIN technique was least affected by comminution, suggesting
      that D-MIN should be used in selecting the diameter of a radial head implant.

PMID- 25591463
TI  - Regulation of CD4 and CD8 coreceptor expression and CD4 versus CD8 lineage
      decisions.
AB  - During blood cell development, hematopoietic stem cells generate diverse mature
      populations via several rounds of binary fate decisions. At each bifurcation,
      precursors adopt one fate and inactivate the alternative fate either
      stochastically or in response to extrinsic stimuli and stably maintain the
      selected fates. Studying of these processes would contribute to better
      understanding of etiology of immunodeficiency and leukemia, which are caused by
      abnormal gene regulation during the development of hematopoietic cells. The
      CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent
      model to study binary fate decision processes. These two cell types are derived
      from common precursors in the thymus. Positive selection of their TCRs by self
      peptide presented on either MHC class I or class II triggers their fate decisions
      along with mutually exclusive retention and silencing of two coreceptors, CD4 and
      CD8. In the past few decades, extensive effort has been made to understand the T
      cell fate decision processes by studying regulation of genes encoding the
      coreceptors and selection processes. These studies have identified several key
      transcription factors and gene regulatory networks. In this chapter, I will
      discuss recent advances in our understanding of the binary cell fate decision
      processes of T cells. 

PMID- 25591464
TI  - Mast cells' integrated actions with eosinophils and fibroblasts in allergic
      inflammation: implications for therapy.
AB  - Mast cells (MCs) and eosinophils (Eos) are the key players in the development of
      allergic inflammation (AI). Their cross-talk, named the Allergic Effector Unit
      (AEU), takes place through an array of soluble mediators and ligands/receptors
      interactions that enhance the functions of both the cells. One of the salient
      features of the AEU is the CD48/2B4 receptor/ligand binding complex. Furthermore,
      MCs and Eos have been demonstrated to play a role not only in AI but also in the
      modulation of its consequence, i.e., fibrosis/tissue remodeling, by directly
      influencing fibroblasts (FBs), the main target cells of these processes. In turn,
      FBs can regulate the survival, activity, and phenotype of both MCs and Eos.
      Therefore, a complex three players, MCs/Eos/FBs interaction, can take place in
      various stages of AI. The characterization of the soluble and physical mediated
      cross talk among these three cells might lead to the identification of both
      better and novel targets for the treatment of allergy and its tissue remodeling
      consequences. 

PMID- 25591465
TI  - Positive-selection-inducing self-peptides displayed by cortical thymic epithelial
      cells.
AB  - A repertoire of antigen recognition specificities in mature T cell pool is formed
      by the selection during T cell development in the thymus. Positive selection is
      an essential process for the development of functionally competent T cells and is
      dependent on the interaction between T cell antigen receptors (TCRs) that newly
      generated thymocytes express and self-peptide-associated major histocompatibility
      complex (pMHC) molecules that cortical thymic epithelial cells (cTECs) express.
      Characterization of positive-selection-inducing peptides has revealed that the
      low-affinity TCR engagement by the positive-selection-inducing pMHC complexes
      initiates intracellular signals that induce the survival of immature thymocytes
      and their differentiation into mature T cells. Recent studies suggest unique
      mechanisms of antigen processing in cTECs for the production of positively
      selecting MHC-bound self-peptides. 

PMID- 25591466
TI  - Group 2 innate lymphoid cells in the regulation of immune responses.
AB  - Type 2 cytokine-driven immune responses are important against parasite infections
      but also underlie the development of inflammatory allergic diseases. Type 2
      CD4(+) T (Th2) cells have long been believed to act as central regulators of
      allergic conditions via the production of the signature cytokines IL-4, IL-5, and
      IL-13. However, the more recent identification of group 2 innate lymphoid cells
      ILC (ILC2) cells, which also produce the same cytokines, necessitates a
      reevaluation of the relative roles these two populations play during type 2
      inflammation. ILC2 cells preferentially localize to the interface between the
      host and the environment (lung, intestine, skin) and respond to epithelium
      derived cytokines associated with barrier disruption, such as IL-25, IL-33, and
      thymic stromal lymphopoietin. ILC2 cells are a major source of IL-5 and IL-13 in
      vivo but may also produce IL-4 and IL-9 under more defined conditions. ILC2 cells
      regulate local inflammatory responses to environmental challenges, and this in
      turn enables them to influence downstream adaptive immune responses. Here, we
      discuss our current understanding of ILC2 cell phenotype, development and
      function, and detail the expanding array of cell surface receptor and signaling
      pathways that enable ILC2 cells to perform a variety of biological functions in
      vivo. We give special attention to the most recently described and poorly
      understood member of the ILC2 cell family, the dermal ILC2 cells, and discuss
      their role in regulating skin inflammation. 

PMID- 25591467
TI  - Microbes and B cell development.
AB  - Animals and many of their chronic microbial inhabitants form relationships of
      symbiotic mutualism, which occurs when coexisting life-forms derive mutual
      benefit from stable associations. While microorganisms receive a secure habitat
      and constant food source from vertebrate hosts, they are required for optimal
      immune system development and occupy niches otherwise abused by pathogens.
      Microbes have also been shown to provide vertebrate hosts with metabolic
      capabilities that enhance energy and nutrient uptake from the diet. The immune
      system plays a central role in the establishment and maintenance of host-microbe
      homeostasis, and B lineage cells play a key role in this regulation. Here, I
      reviewed the structure and function of the microbiota and the known mechanisms of
      how nonpathogenic microbes influence B cell biology and immunoglobulin repertoire
      development early in life. I also discuss what is known about how B lineage cells
      contribute to the process of shaping the composition of commensal/mutualistic
      microbe membership. 

PMID- 25591468
TI  - Iodine deficiency and thyroid disorders.
AB  - Iodine deficiency early in life impairs cognition and growth, but iodine status
      is also a key determinant of thyroid disorders in adults. Severe iodine
      deficiency causes goitre and hypothyroidism because, despite an increase in
      thyroid activity to maximise iodine uptake and recycling in this setting, iodine
      concentrations are still too low to enable production of thyroid hormone. In mild
      to-moderate iodine deficiency, increased thyroid activity can compensate for low
      iodine intake and maintain euthyroidism in most individuals, but at a price:
      chronic thyroid stimulation results in an increase in the prevalence of toxic
      nodular goitre and hyperthyroidism in populations. This high prevalence of
      nodular autonomy usually results in a further increase in the prevalence of
      hyperthyroidism if iodine intake is subsequently increased by salt iodisation.
      However, this increase is transient because iodine sufficiency normalises thyroid
      activity which, in the long term, reduces nodular autonomy. Increased iodine
      intake in an iodine-deficient population is associated with a small increase in
      the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether
      these increases are also transient is unclear. Variations in population iodine
      intake do not affect risk for Graves' disease or thyroid cancer, but correction
      of iodine deficiency might shift thyroid cancer subtypes toward less malignant
      forms. Thus, optimisation of population iodine intake is an important component
      of preventive health care to reduce the prevalence of thyroid disorders. 

PMID- 25591469
TI  - Rationale, design, and baseline characteristics of ARTS-DN: a randomized study to
      assess the safety and efficacy of finerenone in patients with type 2 diabetes
      mellitus and a clinical diagnosis of diabetic nephropathy.
AB  - BACKGROUND/AIMS: Finerenone decreases albuminuria in patients having heart
      failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic
      kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study
      Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter, randomized, double
      blind, placebo-controlled, parallel-group, phase 2b study. ARTS-DN investigated
      whether the mineralocorticoid receptor antagonist finerenone reduces albuminuria
      without causing major alterations in serum potassium levels in patients with type
      2 diabetes mellitus and a clinical diagnosis of DN who were receiving a renin
      angiotensin-system (RAS) inhibitor. METHODS: Patients were randomized to oral
      finerenone 1.25-20 mg or placebo once daily. The primary objectives were to
      assess the ratio of the urinary albumin-to-creatinine ratio at day 90 to that at
      baseline in patients receiving finerenone, and to compare it with that in the
      placebo group. Additional exploratory analyses included evaluating changes from
      baseline in serum potassium levels, efficacy and safety biomarkers, and health
      related quality of life. RESULTS: Of 1,501 patients screened, 821 (the sample
      population) received at least one dose of finerenone/placebo. Baseline
      characteristics included: male, 77.8%; white, 84.2%; very high albuminuria
      (formerly macroalbuminuria), 38.4%; high albuminuria (formerly microalbuminuria),
      60.3%; median (range) estimated glomerular filtration rate, 66.3 (24.5-130.7)
      ml/min/1.73 m(2); and systolic blood pressure (mean +/- standard deviation),
      138.1 +/- 14.4 mm Hg. There was a history of cardiovascular disease in 39.6%,
      diabetic neuropathy in 20.0%, and diabetic retinopathy in 19.9% of patients.
      CONCLUSION: ARTS-DN is the first phase 2b trial of finerenone in combination with
      a RAS inhibitor in patients with type 2 diabetes mellitus and a clinical
      diagnosis of DN.

PMID- 25591470
TI  - Gonadotropin gene transcription is activated by menin-mediated effects on the
      chromatin.
AB  - The genes encoding luteinizing hormone and follicle stimulating hormone are
      activated by gonadotropin-releasing hormone (GnRH), and we hypothesized that this
      involves GnRH-induction of various histone modifications. At basal conditions in
      an immature gonadotrope-derived cell line, the hormone-specific beta-subunit gene
      promoters are densely packed with histones, and contain low levels of H3K4
      trimethylation (H3K4me3). GnRH both induces this modification and causes histone
      loss, creating a more active chromatin state. The H3K4me3 appears to be mediated
      by menin and possibly catalyzed by the menin-mixed-lineage leukemia (MLL) 1/2
      methyl transferase complex, as inhibition of MLL recruitment or menin knockdown
      reduced gene expression and the levels of H3K4me3 on all three promoters. Menin
      recruitment to the beta-subunit gene promoters is increased by GnRH, possibly
      involving transcription factors such as estrogen receptor alpha and/or
      steroidogenic factor 1, with which menin interacts. Menin also interacts with
      ring finger protein 20, which ubiquitylates H2BK120 (H2BK120ub), which was
      reported to be a pre-requisite for H3K4me3 at various gene promoters. Although
      levels of H2BK120ub are increased by GnRH in the coding regions of these genes,
      levels at the promoters do not correlate with those of H3K4me3, nor with gene
      expression, suggesting that H3K4me3 is not coupled to H2BK120ub in
      transcriptional activation of these genes. 

PMID- 25591471
TI  - Part II: Strain- and sex-specific effects of adolescent exposure to THC on adult
      brain and behaviour: Variants of learning, anxiety and volumetric estimates.
AB  - Marijuana is one of the most highly used psychoactive substances in the world,
      and its use typically begins during adolescence, a period of substantial brain
      development. Females across species appear to be more susceptible to the long
      term consequences of marijuana use. Despite the identification of inherent
      differences between rat strains including measures of anatomy, genetics and
      behaviour, no studies to our knowledge have examined the long-term consequences
      of adolescent exposure to marijuana or its main psychoactive component, Delta(9)
      tetrahydrocannabinol (THC), in males and females of two widely used rat strains:
      Long-Evans hooded (LER) and Wistar (WR) rats. THC was administered for 14
      consecutive days following puberty onset, and once they reached adulthood,
      changes in behaviour and in the volume of associated brain areas were quantified.
      Rats were assessed in behavioural tests of motor, spatial and contextual
      learning, and anxiety. Some tasks showed effects of injection, since handled and
      vehicle groups were included as controls. Performance on all tasks, except motor
      learning, and the volume of associated brain areas were altered with injection or
      THC administration, although these effects varied by strain and sex group.
      Finally, analysis revealed treatment-specific correlations between performance
      and brain volumes. This study is the first of its kind to directly compare males
      and females of two rat strains for the long-term consequences of adolescent THC
      exposure. It highlights the importance of considering strain and identifies
      certain rat strains as susceptible or resilient to the effects of THC. 

PMID- 25591472
TI  - Do you believe in brain training? A questionnaire about expectations of
      computerised cognitive training.
AB  - "Brain training" (i.e., enhancing, rehabilitating, or simply maintaining
      cognitive function through deliberate cognitive exercise) is growing rapidly in
      popularity, yet remains highly controversial. Among the greatest problems in
      current research is the lack of a measure of participants' expectations, which
      can influence the degree to which they improve over training (i.e., the placebo
      effect). Here we created a questionnaire to measure the perceived effectiveness
      of brain-training software. Given the growth in advertising of these programmes,
      we sought to determine whether even a brief positive (or negative) message about
      brain training would increase (or decrease) the reported optimism of
      participants. We measured participants' expectations at baseline, and then
      following exposure to separate, brief messages that such programmes have either
      high or low effectiveness. Based on the knowledge they have gleaned from
      advertising and other real-world sources, people are relatively optimistic about
      brain training. However, brief messages can influence reported expectations about
      brain-training results: Reading a brief positive message can increase reported
      optimism, whereas reading a brief negative message can decrease it. Older adults
      appear more optimistic about brain training than young adults, especially when
      they report being knowledgeable about brain training and computers. These data
      indicate that perceptions of brain training are malleable to at least some
      extent, and may vary depending on age and other factors. Our questionnaire can
      serve as a simple, easily-incorporated tool to assess the face validity of brain
      training interventions and to create a covariate to account for expectations in
      statistical analyses. 

PMID- 25591473
TI  - Chronic social isolation decreases glutamate and glutamine levels and induces
      oxidative stress in the rat hippocampus.
AB  - Social isolation (SI) rearing of rodents is a developmental manipulation, which
      is commonly compared with the psychological stressors in humans as it produces
      several behavioral outcomes similar to those observed in humans with early life
      stress. To explain the SI-induced behavioral outcomes, animal studies have been
      performed to examine the dopaminergic and glutamatergic systems in the brain. In
      this study, we measured possible changes in levels of glutamate and glutamine of
      SI-rats using proton magnetic resonance spectroscopy. We also assessed the
      oxidative stress parameters in certain brain regions to see if glutamate and/or
      glutamine changes, if any, are associated with oxidative stress. SI rearing for 8
      weeks decreased the activities of antioxidant enzymes catalase, glutathione
      peroxidase, superoxide dismutase, and the total antioxidant capacity, but
      increased levels of hydrogen peroxide, in certain brain regions, of which
      prefrontal cortex and hippocampus were most vulnerable. It also decreased levels
      of glutamate, glutamine, N-acetyl-l-aspartate (NAA), and phosphocreatine in the
      dorsal hippocampus, but not in the cerebral cortex. Decreased phosphocreatine and
      NAA indicate energy metabolism deficit in brain cells; the latter also suggests
      the neuronal viability was inhibited. Decreased glutamate and glutamine may
      suggest the neuron-glial integrity was implicated by chronic SI. These
      neurochemical and biochemical changes may contribute to the SI-induced behavioral
      abnormalities including a high level of anxiety, social interaction deficit, and
      impaired spatial working memory shown in this study. 

PMID- 25591475
TI  - Ketamine administration during the second postnatal week induces enduring
      schizophrenia-like behavioral symptoms and reduces parvalbumin expression in the
      medial prefrontal cortex of adult mice.
AB  - Dysfunctions in the GABAergic system are considered a core feature of
      schizophrenia. Pharmacological blockade of NMDA receptors (NMDAR), or their
      genetic ablation in parvalbumin (PV)-expressing GABAergic interneurons can induce
      schizophrenia-like behavior in animals. NMDAR-mediated currents shape the
      maturation of GABAergic interneurons during a critical period of development,
      making transient blockade of NMDARs during this period an attractive model for
      the developmental changes that occur in the course of schizophrenia's
      pathophysiology. Here, we examined whether developmental administration of the
      non-competitive NMDAR antagonist ketamine results in persistent deficits in PFC
      dependent behaviors in adult animals. Mice received injections of ketamine
      (30mg/kg) on postnatal days (PND) 7, 9 and 11, and then tested on a battery of
      behavioral experiments aimed to mimic major symptoms of schizophrenia in
      adulthood (between PND 90 and 120). Ketamine treatment reduced the number of
      cells that expressed PV in the PFC by ~60% as previously described. Ketamine
      affected performance in an attentional set-shifting task, impairing the ability
      of the animals to perform an extradimensional shift to acquire a new strategy.
      Ketamine-treated animals showed deficits in latent inhibition, novel-object
      recognition and social novelty detection compared to their SAL-treated
      littermates. These deficits were not a result of generalized anxiety, as both
      groups performed comparably on an elevated plus maze. Ketamine treatment did not
      cause changes in amphetamine-induced hyperlocomotion that are often taken as
      measures for the positive-like symptoms of the disorder. Thus, ketamine
      administration during development appears to be a useful model for inducing
      cognitive and negative symptoms of schizophrenia. 

PMID- 25591474
TI  - Effects of embryonic cyclosporine exposures on brain development and behavior.
AB  - Cyclosporine, a calcineurin inhibitor, is successfully used as an
      immunosuppressant in transplant medicine. However, the use of this pharmaceutical
      during pregnancy is concerning since calcineurin is thought to play a role in
      neural development. The risk for human brain development is difficult to evaluate
      because of a lack of basic information on the sensitive developmental times and
      the potentially pleiotropic effects on brain development and behavior. In the
      present study, we use zebrafish as a model system to examine the effects of
      embryonic cyclosporine exposures. Early embryonic exposures reduced the size of
      the eyes and brain. Late embryonic exposures did not affect the size of the eyes
      or brain, but did lead to substantial behavioral defects at the larval stages.
      The cyclosporine-exposed larvae displayed a reduced avoidance response to visual
      stimuli, low swim speeds, increased resting, an increase in thigmotaxis, and
      changes in the average distance between larvae. Similar results were obtained
      with the calcineurin inhibitor FK506, suggesting that most, but not all, effects
      on brain development and behavior are mediated by calcineurin inhibition.
      Overall, the results show that cyclosporine can induce either structural or
      functional brain defects, depending on the exposure window. The observed
      functional brain defects highlight the importance of quantitative behavioral
      assays when evaluating the risk of developmental exposures. 

PMID- 25591476
TI  - Relevance of the metabotropic glutamate receptor (mGluR5) in the regulation of
      NREM-REM sleep cycle and homeostasis: evidence from mGluR5 (-/-) mice.
AB  - Sleep is a homeostatically regulated behavior and sleep loss evokes a
      proportional increase in sleep time and delta slow wave activity. Glutamate and
      pharmacological modulation of the metabotropic glutamate receptors (mGluR)
      signaling have been implicated in the organization of vigilance states. Here, the
      role of the mGluR5 on homeostatic regulation of sleep-wake cycle and
      electroencephalographic (EEG) activity was examined in mGluR5 (-/-) mice. We
      first characterized the sleep-wake EEG phenotype in mGluR5 (-/-) and wild-type
      (WT) littermates mice by continuous recording for 72h of EEG, body temperature
      (BT) and locomotor activity (LMA). Next, we investigated the influence of sleep
      deprivation on the recovery sleep and EEG slow wave activity (1-4Hz) during NREM
      sleep to assess whether mGluR5 deletion affects the sleep homeostasis process.
      Like the control animals, mGluR5 (-/-) mice exhibited a clear-cut circadian sleep
      wake architecture, however they showed reduced REM sleep time during the light
      phase with shorter REM sleep bouts and reduced state transitions in the NREM
      sleep-REM sleep cycle during the first and last 24h of the spontaneous 72h
      recording period. In addition, mGluR5 (-/-) mice had decreased slow EEG delta
      power during NREM sleep and enhanced LMA associated with elevated BT during the
      dark phase. Moreover, mGluR5 (-/-) mice exhibited reduced slow wave activity and
      sleep drive after sleep deprivation, indicating altered sleep homeostatic
      processes. The findings strongly indicate that mGluR5 is involved in shaping the
      stability of NREM sleep-REM sleep state transitions, NREM slow wave activity and
      homeostatic response to sleep loss. 

PMID- 25591477
TI  - Delineation of the working memory profile in female FMR1 premutation carriers:
      the effect of cognitive load on ocular motor responses.
AB  - Fragile X mental retardation 1 (FMR1) premutation carriers (PM-carriers) are
      characterised as having mid-sized expansions of between 55 and 200 CGG repeats in
      the 5' untranslated region of the FMR1 gene. While there is evidence of executive
      dysfunction in PM-carriers, few studies have explicitly explored working memory
      capabilities in female PM-carriers. 14 female PM-carriers and 13 age- and IQ
      matched healthy controls completed an ocular motor n-back working memory
      paradigm. This task examined working memory ability and the effect of measured
      increases in cognitive load. Female PM-carriers were found to have attenuated
      working memory capabilities. Increasing the cognitive load did not elicit the
      expected reciprocal increase in the task errors for female PM-carriers, as it did
      in controls. However female PM-carriers took longer to respond than controls,
      regardless of the cognitive load. Further, FMR1 mRNA levels were found to
      significantly predict PM-carrier response time. Although preliminary, these
      findings provide further evidence of executive dysfunction, specifically
      disruption to working memory processes, which were found to be associated with
      increases in FMR1 mRNA expression in female PM-carriers. With future validation,
      ocular motor paradigms such as the n-back paradigm will be critical to the
      development of behavioural biomarkers for identification of PM-carrier cognitive
      affective phenotypes. 

PMID- 25591478
TI  - The kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), decreases
      morphine withdrawal and the consequent conditioned place aversion in rats.
AB  - Much data suggest that the binding of dynorphin-like peptides to kappa-opioid
      receptors (KORs) during the administration of and withdrawal from a variety of
      addictive drugs is aversive and serves to limit the reinforcing properties of
      those drugs and to enhance tolerance, withdrawal, and the probability of stress
      induced relapse. In this study, we examined the role of KORs in mediating opioid
      withdrawal and its aversive consequences in rats. We found that selective
      blockade of KORs by i.p. administration of 20mg/kg nor-binaltorphimine (nor-BNI)
      5h prior to naltrexone-precipitated withdrawal in morphine-dependent rats
      decreased feces excreted during a 30-min withdrawal session. More critically,
      this injection of nor-BNI decreased the subsequent conditioned place aversion
      (CPA) for the withdrawal chamber 2 days later. The subsequent finding that
      administration of nor-BNI 2h following withdrawal did not affect the CPA 2 days
      later suggested that nor-BNI reduced the CPA in the prior experiment because it
      reduced the aversive effects of withdrawal, not because it reduced the
      aversive/anxiogenic effects of the withdrawal chamber at the time of CPA testing.
      These data indicate that the binding of dynorphin-like peptides to KORs during
      opioid withdrawal serves to enhance withdrawal and its aversive consequences and
      suggest that selective KOR antagonists may be useful in reducing these aversive
      effects and consequent relapse.

PMID- 25591481
TI  - CORRIGENDUM: Large Linear Magnetoresistance and Shubnikov-de Hass Oscillations in
      Single Crystals of YPdBi Heusler Topological Insulators.

PMID- 25591479
TI  - Dose-dependent effects of the antiprogestin, RU486, on sexual behavior of
      naturally cycling Fischer rats.
AB  - Regularly cycling Fischer female rats were treated with either a low (5mg/kg) or
      high (5mg/RAT; approximately 30mg/kg) dose of the antiprogestin, RU486, before
      the morning of proestrus or on the morning of proestrus. The emergence of sexual
      behavior after treatment with RU486 was examined in a mating test with a sexually
      active male rat. Lordosis behavior was remarkably resistant to the effects of
      RU486. Only the high dose of RU486 given the evening before proestrus,
      approximately 22h before mating, reduced lordosis behavior. Independent of dose
      or time of treatment, proceptivity was reduced and resistance to the male's
      attempts to mount was increased by RU486 treatment. In addition, the effect of a
      5min restraint stress on sexual behavior was examined. In contrast to the
      relative resistance of lordosis behavior of unrestrained rats to RU486 treatment,
      RU486 treated rats showed a significant decline in lordosis behavior after
      restraint. These findings allow the suggestion that the emergence of lordosis
      behavior is relatively resistant to the antiprogestin while the maintenance of
      lordosis behavior after restraint may require participation of intracellular
      progesterone receptors. 

PMID- 25591480
TI  - Sex-specific impairment and recovery of spatial learning following the end of
      chronic unpredictable restraint stress: potential relevance of limbic GAD.
AB  - Chronic restraint stress alters hippocampal-dependent spatial learning and memory
      in a sex-dependent manner, impairing spatial performance in male rats and leaving
      intact or facilitating performance in female rats. Moreover, these stress-induced
      spatial memory deficits improve following post-stress recovery in males. The
      current study examined whether restraint administered in an unpredictable manner
      would eliminate these sex differences and impact a post-stress period on spatial
      ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30)
      and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control
      (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery
      period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using
      daily non-repeated combinations of physical context, duration, and time of day.
      Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and
      given one retention trial on the third day, with brains removed 30min later to
      assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM
      acquisition, an impairment that was not evident in the Str-Rec group. In
      contrast, females did not show significant outcomes following chronic stress or
      post-stress recovery. In males, amygdalar GAD65 expression negatively correlated
      with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively
      correlated with RAWM performance on day 1. These results demonstrate that
      GABAergic function may contribute to the sex differences observed following
      chronic stress. Furthermore, unpredictable restraint and a recovery period failed
      to eliminate the sex differences on spatial learning and memory. 

PMID- 25591482
TI  - The reaction of cerebral cortex to a nearby lesion: damage, survival, self
      protection.
AB  - A needlestick injury to cerebral cortex causes immediate damage along the track
      of the needle (haemorrhage, cell death) and sequelae (the formation of amyloid
      positive plaques, extracellular deposits of hyperphosphorylated tau protein,
      microglial proliferation, astrogliosis) that are long lasting, and mimic the
      neuropathology associated with Alzheimer's disease. We report here that the same
      injury also elicits a distinctive response in the cortex flanking (up to 1mm
      from) the direct injury. Needlestick injury was made in the neo- and hippocampal
      cortex of young (3 months) healthy Sprague-Dawley rats. After survival times of
      up to 7d, the response of the cortex was assessed with histology,
      immunohistochemistry and stereology. Uptake of FluoroJade B at 1d survival and
      labelling for 4-hydroxynonenal (4-HNE) gave measures of membrane damage;
      labelling for 8-hydroxy-2'-deoxyguanosine (8-OHDG) gave a measure of DNA damage,
      and labelling with the AT8 antibody gave a measure of the hyperphosphorylation of
      tau. Two probes, for neuroglobin and basic fibroblast growth factor (FGF-2), gave
      measures of a self-protective response in the tissue. Results indicate that
      neurones in the flanking region are damaged by the nearby lesion, and within 1d
      upregulate self-protective mechanisms. Over the next 6d survival, evidence of
      neuronal damage reduces markedly. In summary, cells in the region flanking a
      lesion are stressed by the lesion, and react to the stress with a self-protective
      response, which prevents their death. This response may be an important,
      previously unrecognised feature of brain tissue close to a focus of stress, such
      as a microhaemorrhage.

PMID- 25591483
TI  - Repair of spinal cord injury with neuronal relays: From fetal grafts to neural
      stem cells.
AB  - Spinal cord injury (SCI) disrupts the long axonal tracts of the spinal cord
      leading to devastating loss of function. Cell transplantation in the injured
      spinal cord has the potential to lead to recovery after SCI via a variety of
      mechanisms. One such strategy is the formation of neuronal relays between injured
      long tract axons and denervated neurons. The idea of creating a neuronal relay
      was first proposed over 25 years ago when fetal tissue was first successfully
      transplanted into the injured rodent spinal cord. Advances in labeling of grafted
      cells and the development of neural stem cell culturing techniques have improved
      the ability to create and refine such relays. Several recent studies have
      examined the ability to create a novel neuronal circuit between injured axons and
      denervated targets. This approach is an alternative to long-distance regeneration
      of damaged axons that may provide a meaningful degree of recovery without direct
      recreation of lost pathways. This brief review will examine the contribution of
      fetal grafting to current advances in neuronal grafting. Of particular interest
      will be the ability of transplanted neurons derived from fetal grafts, neural
      precursor cells and neural stem cells to reconnect long distance motor and
      sensory pathways of the injured spinal cord. This article is part of a Special
      Issue entitled SI: Spinal cord injury. 

PMID- 25591485
TI  - Outcomes after long-term follow-up of combat-related extremity injuries in a
      multidisciplinary limb salvage clinic.
AB  - BACKGROUND: Although the incidence of casualties from the Global War on Terror is
      decreasing, there remains a focus on the long-term sequelae from injuries
      sustained in the combat. Patients with prior significant limb injuries remain at
      risk of future complications. This study examines our institution's experience
      with a multidisciplinary team approach toward this challenging patient
      population. METHODS: A retrospective review was performed on all patients treated
      in a single institution Limb Preservation Clinic over a 2-year period. Those
      patients who sustained a combat-related injury in theater were examined. Patient
      demographics, mechanism of injury, amputation rates, time to amputation, and
      reasons for failure were examined. RESULTS: Ninety-four patients were evaluated
      in our multidisciplinary Limb Preservation Clinic over a 2-year period. Twenty
      patients (21%) were seen for combat-related injuries. Sixteen patients were
      evaluated and treated for chronic complications at a median of 13 months from
      their injury. All 16 patients were male with a median age of 24 years (range, 20
      35). Ten patients sustained injuries secondary to a dismounted improvised
      explosive device (IED). All 16 patients had extensive soft tissue injuries and
      associated fractures. Only 2 patients sustained a vascular injury. The median
      number of prior surgeries to the affected limb was 8 (range, 3-19). The limb
      salvage rate of 37% was lower than our noncombat cohort (47%). The most common
      reasons for delayed amputation included chronic pain, osteomyelitis, and soft
      tissue infections. CONCLUSIONS: The high secondary amputation rates seen in this
      cohort underscores the need for long-term follow-up. Despite successful initial
      outcomes, many patients eventually progress to limb loss. Patients who sustain a
      dismounted IED are at greatest risk for a delayed amputation. Identifying and
      addressing those factors which lead to delayed amputation should be a priority
      for returning war veterans and focus of future studies.

PMID- 25591484
TI  - Do slow and fast gamma rhythms correspond to distinct functional states in the
      hippocampal network?
AB  - For decades, hippocampal gamma was thought to be a single type of rhythm with a
      continuously varying frequency. However, an increasing body of evidence supports
      a new hypothesis regarding hippocampal gamma. The patterns traditionally defined
      as hippocampal gamma may actually comprise separate gamma subtypes with distinct
      frequencies and unique functions. The present review discusses the evidence for
      and against this new viewpoint. This review will also point out key questions
      that remain to be answered to validate the two-gamma hypothesis. This article is
      part of a Special Issue entitled SI: Brain and Memory. 

PMID- 25591486
TI  - Volumetric assessment of the carotid bifurcation: an alternative concept to
      stenosis grading.
AB  - BACKGROUND: To design a volumetric method for the assessment of carotid
      atheromatosis (CA) based on computed tomography (CT) angiography and three
      dimensional (3D) reconstructions; to analyze the accuracy and optimal threshold
      values to differentiate between equivalent degrees of severity by duplex scanning
      and CT angiography (two-dimensional maximum intensity projection [2D MIP];
      internal carotid artery stenosis [ICS] <50%; ICS >50%); and to assess the
      method's suitability to detect progression of CA. METHODS:  DESIGN: suitability
      and accuracy of a new diagnostic method. POPULATION: 90 carotid bifurcations (45
      patients) were assessed with duplex scanning and CT angiography, and reevaluated
      after 12 +/- 2 months follow-up. Determinations: Assessment of internal carotid
      artery (ICA) stenosis degree with duplex scanning and 2D MIP CT angiography
      projections. Volumetric assessment of carotid bifurcation by CT angiography
      (contrast volume [mm(3)] and density [Hounsfield units, H.U.] between 2-cm below
      and 1-cm above the anatomic bifurcation of the carotid artery [BifV], and its
      ratio with 1-cm segment of the common carotid artery [CCV]). STATISTICAL
      ANALYSIS: descriptive statistics; intraobserver and interobserver agreement
      (Bland-Altman plot and intraclass correlation coefficient [ICC], accuracy of 3D
      volumetry and duplex scanning as referred to MIP 2D CT angiography as gold
      standard: sensitivity (Sens), specificity (Sp), kappa index, and receiver
      operating characteristic curves (ROCs). RESULTS: Estimation of MIP 2D images (CT
      angiography) confirmed the findings of duplex scanning in 23 of 30 ICS <50% and
      48 of 53 ICS >50% (Sens, 0.91; Sp, 0.77% kappa = 0.68). Three-dimensional
      volumetric assessment of carotid bifurcation showed an intraobserver and
      interobserver agreement with an ICC of 0.96 (95% confidence interval [CI], 0.904
      0.985) and 0.94 (95% CI, 0.822-0.977), respectively. The BifV-to-CCV ratio was
      5.2 +/- 1.8 in the ICS <50% group versus 3.8 +/- 1.3 in the ICS >50% group (P =
      0.001). The optimal cutoff point of the BifV-to-CCV relationship was identified
      from the ROC curve in 4.1 (Sens, 0.75; Sp, 0.75; kappa, 0.46). At 12 months, a
      decrease of the average BifV with regard to the baseline value (475.45 [155.6]
      mm(3) * H.U. vs. 501.3 [171.9] mm(3) * H.U.; P = 0.04) was observed. CA
      progression was detected in 32 bifurcations (14 ICS <50%; 18 ICS> 50%), with a
      reduced bifurcation volume of 137.8 (71.4) mm(3) * H.U.; P < 0.001. CONCLUSIONS:
      Volumetric assessment of carotid bifurcation is a new concept based on assessing
      plaque burden rather than its hemodynamic effect or maximum stenosis; thus,
      justifying its moderate accuracy with regard to ICS conventional ICA grading
      based on biplanar images. This method can be especially useful in plaque
      progression studies given its accuracy to detect minor changes in the arterial
      lumen.

PMID- 25591487
TI  - The impact of carotid artery stenting on cognitive function in patients with
      extracranial carotid artery stenosis.
AB  - BACKGROUND: The effect of carotid artery stenting (CAS) on cognitive function in
      patients with extracranial carotid artery stenosis is equivocal. The aim of this
      study was to examine the impact of CAS on various domains of cognitive function.
      METHODS: We performed a meta-analysis of the studies evaluating various domains
      of cognitive function before and after CAS, namely, (1) global cognition using
      Mini-Mental State Examination (MMSE) and Rey Auditory Verbal Learning Test
      (RAVLT), (2) executive function using Trail Making Test (TMT) A or Color Trails
      Test (CTT) A and TMT B or CTT B, (3) language ability using Boston Naming Test
      (BNT), (4) memory, (5) attention/psychomotor speed, and (6) functional ability,
      using various cognitive tests. Pooled weighted mean differences (WMDs) and
      standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were
      appropriately calculated using fixed or random effects models after assessing
      between-study heterogeneity. Meta-regression analysis was performed with number
      of patients per study; mean age (years); follow-up (months); proportion of men;
      proportion of patients with hypertension, diabetes mellitus, hyperlipidemia,
      smoking, and coronary artery disease; proportion of symptomatic patients; and
      degree of ipsilateral and degree of contralateral carotid stenosis as covariates.
      RESULTS: Sixteen studies were eligible, including a total of 626 CAS patients. A
      statistically significant improvement of global cognition was detected with MMSE
      (WMD = 0.67, 95% CI = 0.29-1.05, P < 0.001; follow-up = 5.6 months), but not with
      RAVLT (SMD = 0.45, 95% CI = -0.03 to 0.93, P = 0.07; follow-up = 2.4 months).
      Significant improvement of memory (SMD = 0.33, 95% CI = 0.11-0.55, P < 0.01;
      follow-up = 4.1 months) and attention/psychomotor speed (SMD = 0.21, 95% CI =
      0.04-0.39, P = 0.02; follow-up = 4 months) was also detected. No statistically
      significant effect on executive function (TMT A/CTT A and TMT B/CTT B; SMD =
      0.08, 95% CI = -0.10 to 0.26, P = 0.39; follow-up = 3.9 months and SMD = -0.02,
      95% CI = -0.20 to 0.16, P = 0.82, respectively; follow-up = 3.9 months), language
      ability (BNT; SMD = 0.24, 95% CI = -0.05 to 0.54, P = 0.10; follow-up = 4
      months), and functional ability (SMD = -0.05, 95% CI = -0.25 to 0.15, P = 0.63;
      follow-up = 3.8 months) was observed. No significant effects of the examined
      covariates were demonstrated in the meta-regression analyses. CONCLUSIONS: CAS
      may be associated with improvement in global cognition, memory, and
      attention/psychomotor speed. There was no positive effect on executive function,
      language, and functional ability, but CAS was not associated with a decline in
      any area of cognitive function. Future studies in larger groups of patients are
      probably needed to fully investigate the long-term effect of CAS on cognition in
      patients with carotid artery stenosis.

PMID- 25591488
TI  - Utility of electrofusion for the femoral approach in vascular surgery: a
      randomized prospective study.
AB  - BACKGROUND: The local complications are frequent after a femoral approach in
      vascular surgery and are often the cause of a delay in healing. Electrofusion
      showed its effectiveness to decrease the complications in general surgery but was
      not tested in vascular surgery. The aim of our study was to evaluate if the use
      of electrofusion in the approach to femoral vessels improved healing at 1 month
      by decreasing the local complications. METHODS: This prospective randomized study
      was conducted in 2 centers from May 1, 2012 to April 30, 2013. All the patients
      requiring a surgical access of the femoral trigone were included in 2 French
      teaching hospitals. Femoral artery surgical exposure was carried out using
      electrofusion or according to the conventional technique (diathermy or cold
      scalpel) according to a protocol of randomization. The principle criterion of the
      study was a complete healing at 1 month. The secondary criteria were the
      appearance of cutaneous, infectious, or lymphatic local complications. RESULTS:
      Two hundred ninety-two femoral approaches were carried out in 221 consecutive
      patients. One hundred forty-eight approaches were carried out with electrofusion
      and 144 according to the conventional technique. The demographic and operative
      characteristics were similar between the 2 groups. At 1 month, 86.3% of the
      approaches were healed without statistically significant difference between the 2
      groups (88.5% vs. 84%, P = 0.241). There were less local complications (P =
      0.012) and seromas (P = 0.012) in the electrofusion group. This difference could
      be linked with the least quantities (P = 0.036) and durations (P = 0.014) of
      drainage observed after approaches carried out with electrofusion. On the other
      hand, the incidence of cutaneous or infectious complications was not different
      between the 2 groups. CONCLUSIONS: In our series, the use of electrofusion
      decreased the lymphatic complications after a femoral approach. However, the
      correction of this single parameter was not sufficient to improve the rate of
      healing at 1 month.

PMID- 25591489
TI  - Art tells the story of vaccines.

PMID- 25591490
TI  - Bed bug outbreak in a neonatal unit.
AB  - There has been a worldwide increase in bed bug infestations over the last 10-15
      years. A major stigma is placed upon the institutions found to be infested. We
      report our experience with an outbreak of the tropical bed bug, Cimex hemipterus,
      in a neonatal unit. The outbreak not only affected the admitted newborns and
      mothers by causing a wide variety of rashes and inducing sleeplessness, but also
      impinged upon the health professionals and their families by producing similar
      symptomology. It is important for healthcare providers to be aware of, and for
      each healthcare facility to have, bed bug prevention and control policies. 

PMID- 25591491
TI  - Repurposing a bacterial quality control mechanism to enhance enzyme production in
      living cells.
AB  - Heterologous expression of many proteins in bacteria, yeasts, and plants is often
      limited by low titers of functional protein. To address this problem, we have
      created a two-tiered directed evolution strategy in Escherichia coli that enables
      optimization of protein production while maintaining high biological activity.
      The first tier involves a genetic selection for intracellular protein stability
      that is based on the folding quality control mechanism inherent to the twin
      arginine translocation pathway, while the second is a semi-high-throughput screen
      for protein function. To demonstrate the utility of this strategy, we isolated
      variants of the endoglucanase Cel5A, from the plant-pathogenic fungus Fusarium
      graminearum, whose production was increased by as much as 30-fold over the
      parental enzyme. This gain in production was attributed to just two amino acid
      substitutions, and it was isolated after two iterations through the two-tiered
      approach. There was no significant tradeoff in activity on soluble or insoluble
      cellulose substrates. Importantly, by combining the folding filter afforded by
      the twin-arginine translocation quality control mechanism with a function-based
      screen, we show enrichment for variants with increased protein abundance in a
      manner that does not compromise catalytic activity, providing a highly soluble
      parent for engineering of improved or new function. 

PMID- 25591493
TI  - Treatment of Traumatic Brain Injury-Induced Dyskinesia With Tetrabenazine: A Case
      Report.

PMID- 25591492
TI  - Critical analysis of the efficacy of meditation therapies for acute and subacute
      phase treatment of depressive disorders: a systematic review.
AB  - BACKGROUND: Recently, the application of meditative practices to the treatment of
      depressive disorders has met with increasing clinical and scientific interest,
      owing to a lower side-effect burden, potential reduction of polypharmacy, and
      theoretical considerations that such interventions may target some of the
      cognitive roots of depression. OBJECTIVE: We aimed to determine the state of the
      evidence supporting this application. METHODS: Randomized controlled trials of
      techniques meeting the Agency for Healthcare Research and Quality definition of
      meditation, for participants having clinically diagnosed depressive disorders,
      not currently in remission, were selected. Meditation therapies were separated
      into praxis (i.e., how they were applied) components, and trial outcomes were
      reviewed. RESULTS: 18 studies meeting the inclusion criteria were identified,
      encompassing 7 distinct techniques and 1173 patients. Mindfulness-Based Cognitive
      Therapy comprised the largest proportion of studies. Studies including patients
      having acute major depressive episodes (n = 10 studies), and those with residual
      subacute clinical symptoms despite initial treatment (n = 8), demonstrated
      moderate to large reductions in depression symptoms within the group, and
      relative to control groups. There was significant heterogeneity of techniques and
      trial designs. CONCLUSIONS: A substantial body of evidence indicates that
      meditation therapies may have salutary effects on patients having clinical
      depressive disorders during the acute and subacute phases of treatment. Owing to
      methodologic deficiencies and trial heterogeneity, large-scale, randomized
      controlled trials with well-described comparator interventions and measures of
      expectation are needed to clarify the role of meditation in the depression
      treatment armamentarium.

PMID- 25591494
TI  - Decisional capacity in pregnancy: a complex case of pregnancy termination.

PMID- 25591495
TI  - The recognition and treatment of rabies: a case report and discussion.

PMID- 25591496
TI  - A preliminary investigation of schematic beliefs and unusual experiences in
      children.
AB  - BACKGROUND: In cognitive models of adult psychosis, schematic beliefs about the
      self and others are important vulnerability and maintaining factors, and are
      therefore targets for psychological interventions. Schematic beliefs have not
      previously been investigated in children with distressing unusual, or psychotic
      like, experiences (UEDs). The aim of this study was firstly to investigate
      whether a measure of schematic beliefs, originally designed for adults with
      psychosis, was suitable for children; and secondly, to examine the association of
      childhood schematic beliefs with internalising and externalising problems and
      with UEDs. METHOD: Sixty-seven children aged 8-14 years, with emotional and
      behavioural difficulties, completed measures of UEDs, internalising (depression
      and anxiety), and externalising (conduct and hyperactivity-inattention) problems,
      together with the Brief Core Schema Scales (BCSS). RESULTS: The BCSS was readily
      completed by participants, and scale psychometric properties were good. Children
      tended to view themselves and others positively. Internalising and externalising
      problems and UEDs were all associated with negative schematic beliefs; effect
      sizes were small to medium. CONCLUSIONS: Schematic beliefs in young people can be
      measured using the BCSS, and negative schematic beliefs are associated with
      childhood psychopathology and with UEDs. Schematic beliefs may therefore form a
      useful target in psychological interventions for young people with UEDs.

PMID- 25591497
TI  - Quantitative polymerase chain reaction analysis with allele-specific
      oligonucleotide primers for individual IgH VDJ regions to evaluate tumor burden
      in myeloma patients.
AB  - Quantitative polymerase chain reaction (PCR) with patient-specific, allele
      specific oligonucleotide (ASO) primers for individual immunoglobulin H VDJ region
      (ASO-PCR) amplification was performed using several sources of clinical material,
      including mRNA from peripheral blood cells (PBMNCs), whole bone marrow cells
      (BMMNCs), and the CD20+ CD38- B-cell population in bone marrow, as well as cell
      free DNA from the sera of patients with multiple myeloma (MM). We designed the
      ASO primers and produced sufficient PCR fragments to evaluate tumor burden in 20
      of 30 bone marrow samples at diagnosis. Polymerase chain reaction amplification
      efficiency depended on primer sequences because the production of ASO-PCR
      fragments did not correlate with serum M-protein levels. However, the ASO-PCR
      levels in BMMNCs showed statistically significant correlations with those in
      PBMNCs and CD20+ CD38- B-cells. The good association between the BMMNC and PBMNC
      data indicated that PBMNCs could be a suitable source for monitoring minimal
      residual disease (MRD). In the case of cell-free DNA, ASO-PCR levels showed a
      unique pattern and remained high even after treatment. Because the sequence
      information for each ASO-PCR product was identical to the original, the cell-free
      DNA might also be useful for evaluating MRD. Moreover, the ASO-PCR products were
      clearly detected in 17 of 22 mRNA samples from CD20+ CD38- populations,
      suggesting that MM clones might exist in relatively earlier stages of B cells
      than in plasma cells. Thus, ASO-PCR analysis using various clinical materials is
      useful for detecting MRD in MM patients as well as for clarifying MM
      pathogenesis.

PMID- 25591498
TI  - Loss of autophagy leads to failure in megakaryopoiesis, megakaryocyte
      differentiation, and thrombopoiesis in mice.
AB  - During hematopoiesis, megakaryopoiesis, megakaryocyte differentiation, and
      thrombopoiesis are regulated at multiple stages, which involve successive lineage
      commitment steps and proceed with polyploidization, maturation, and organized
      fragmentation of the cytoplasm, leading to the release of platelets in
      circulation. However, the cellular mechanisms by which megakaryocytes derive from
      their progenitors and differentiate into platelets have not fully been
      understood. Using an Atg7 hematopoietic conditional knockout mouse model, we
      found that loss of autophagy, a metabolic process essential in homeostasis and
      cellular remodeling, caused mitochondrial and cell cycle dysfunction, impeding
      megakaryopoiesis and megakaryocyte differentiation, as well as thrombopoiesis and
      subsequently produced abnormal platelets, larger in size and fewer in number,
      ultimately leading to severely impaired platelet production and failed
      hemostasis. 

PMID- 25591500
TI  - Solvation dynamics and energetics of intramolecular hydride transfer reactions in
      biomass conversion.
AB  - Hydride transfer changes the charge structure of the reactant and thus, may
      induce reorientation/reorganization of solvent molecules. This solvent
      reorganization may in turn alter the energetics of the reaction. In the present
      work, we investigate the intramolecular hydride transfer by taking Lewis acid
      catalyzed glucose to fructose isomerization as an example. The C2-C1 hydride
      transfer is the rate limiting step in this reaction. Water and methanol are used
      as solvents and hydride transfer is simulated in the presence of explicit solvent
      molecules, treated quantum mechanically and at a finite temperature, using Car
      Parrinello molecular dynamics (CPMD) and metadynamics. Activation free energy
      barrier for hydride transfer in methanol is found to be 50 kJ mol(-1) higher than
      that in water. In contrast, in density functional theory calculations, using an
      implicit solvent environment, the barriers are almost identical. Analysis of
      solvent dynamics and electronic polarization along the molecular dynamics
      trajectory and the results of CPMD-metadynamics simulation of the hydride
      transfer process in the absence of any solvent suggest that higher barrier in
      methanol is a result of non-equilibrium solvation. Methanol undergoes electronic
      polarization during the hydride transfer step. However, its molecular
      orientational relaxation is a much slower process that takes place after the
      hydride transfer, over an extended timescale. This results in non-equilibrium
      solvation. Water, on the other hand, does not undergo significant electronic
      polarization and thus, has to undergo minimal molecular reorientation to provide
      near equilibrium solvation to the transition state and an improved equilibrium
      solvation to the post hydride shift product state. Hence, the hydride transfer
      step is also observed to be exergonic in water and endergonic in methanol. The
      aforementioned explanation is juxtaposed to enzyme catalyzed charge transfer
      reactions, where the enhanced solvation of the transition and product states by
      enzymes, due to electrostatic interactions, reduces the activation free energy
      barrier and the free energy change of the reaction. Similarly, we suggest that,
      in the intramolecular hydride shift, improved solvation of the transition state
      and of the product state by water is achieved due to minimal polarization and
      reorientation, and (near) equilibrium solvation. 

PMID- 25591499
TI  - Behavioral stage of change and dialysis decision-making.
AB  - BACKGROUND AND OBJECTIVES: Behavioral stage of change (SoC) algorithms classify
      patients' readiness for medical treatment decision-making. In the
      precontemplation stage, patients have no intention to take action within 6
      months. In the contemplation stage, action is intended within 6 months. In the
      preparation stage, patients intend to take action within 30 days. In the action
      stage, the change has been made. This study examines the influence of SoC on
      dialysis modality decision-making. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      SoC and relevant covariates were measured, and associations with dialysis
      decision-making were determined. In-depth interviews were conducted with 16
      patients on dialysis to elicit experiences. Qualitative interview data informed
      the survey design. Surveys were administered to adults with CKD (eGFR<=25
      ml/min/1.73 m(2)) from August, 2012 to June, 2013. Multivariable logistic
      regression modeled dialysis decision-making with predictors: SoC, provider
      connection, and dialysis knowledge score. RESULTS: Fifty-five patients completed
      the survey (71% women, 39% white, and 59% black), and median annual income was
      $17,500. In total, 65% of patients were in the precontemplation/contemplation
      (thinking) and 35% of patients were in the preparation/maintenance (acting) SoC;
      62% of patients had made dialysis modality decisions. Doctors explaining modality
      options, higher dialysis knowledge scores, and fewer lifestyle barriers were
      associated with acting versus thinking SoC (all P<0.02). Patients making modality
      decisions had doctors who explained dialysis options (76% versus 43%), were in
      the acting versus the thinking SoC (50% versus 10%), had higher dialysis
      knowledge scores (1.4 versus 0.5), and had lower eGFR (13.9 versus 16.8
      ml/min/1.73 m(2); all P<0.05). In adjusted analyses, dialysis knowledge was
      significantly associated with decision-making (odds ratio, 4.2; 95% confidence
      interval, 1.4 to 12.9; P=0.01), and SoC was of borderline significance (odds
      ratio, 5.8; 95% confidence interval, 1.0 to 32.6; P=0.05). The model C statistic
      was 0.87. CONCLUSIONS: Dialysis decision-making was associated with SoC, dialysis
      knowledge, and physicians discussing treatment options. Future studies
      determining ways to assist patients with CKD in making satisfying modality
      decisions are warranted.

PMID- 25591502
TI  - New and different publication types are possible in the near future.

PMID- 25591501
TI  - The influence of training and experience on memory strategy.
AB  - This paper investigates whether, and if so how much, prior training and
      experience overwrite the influence of the constraints of the task environment on
      strategy deployment. This evidence is relevant to the theory of soft constraints
      that focuses on the role of constraints in the task environment (Gray, Simms, Fu,
      & Schoelles, Psychological Review, 113: 461-482, 2006). The theory explains how
      an increase in the cost of accessing information induces a more memory-based
      strategy involving more encoding and planning. Experiments 1 and 3 adopt a
      traditional training and transfer design using the Blocks World Task in which
      participants were exposed to training trials involving a 2.5-s delay in accessing
      goal-state information before encountering transfer trials in which there was no
      access delay. The effect of prior training was assessed by the degree of memory
      based strategy adopted in the transfer trials. Training with an access delay had
      a substantial carry-over effect and increased the subsequent degree of memory
      based strategy adopted in the transfer environment. However, such effects do not
      necessarily occur if goal-state access cost in training is less costly than in
      transfer trials (Experiment 2). Experiment 4 used a fine-grained intra-trial
      design to examine the effect of experiencing access cost on one, two, or three
      occasions within the same trial and found that such experience on two consecutive
      occasions was sufficient to induce a more memory-based strategy. This paper
      establishes some effects of training that are relevant to the soft constraints
      theory and also discusses practical implications. 

PMID- 25591503
TI  - Outrage....

PMID- 25591504
TI  - Shorter treatments for hepatitis C: another step forward?

PMID- 25591506
TI  - Human umbilical cord and dental pulp-derived mesenchymal stem cells: biological
      characteristics and potential roles in vitro and in vivo.
AB  - Mesenchymal stem/stromal cells (MSCs) have a wide application in cell-based
      therapies and tissue engineering. In the present study, the differentiation,
      survivin (SVV)-modified effects and molecular basis of human umbilical cord
      derived MSCs (HUMSCs) and dental pulp-derived stem cells (DPSCs) were
      investigated. The HUMSCs were found to differentiate into adipocytes more readily
      than the DPSCs and the HUMSCs and DPSCs were each able to differentiate into
      osteoblasts and chondroblasts. Following modification of the MSCs by SVV, the
      secretion of SVV in the modified HUMSCs was significantly higher compared with
      that in the modified DPSCs. In vivo, survival of the SVV-modified DPSCs was
      observed at 4 and 14 days after intrastriatal transplantation, as was the
      expression of SVV and differentiation into astrocytes. The gene expression
      profiles of the control and modified HUMSCs and DPSCs were compared using RNA
      sequencing and an association was observed between gene expression and
      variability in cell line function. These findings provide novel information
      regarding the differences between HUMSCs and DPSCs and insight into optimal cell
      sources for therapeutic applications.

PMID- 25591508
TI  - [Clinical features of peripheral neuropathy in paraproteinemic hemoblastosis].
AB  - OBJECTIVE: Peripheral neuropathy often occurs as a side effect of medication or
      as a manifestation of system disease. The purpose of this study was to evaluate
      the features of polyneuropathy with verified paraproteinemic hemoblastosis.
      MATERIAL AND METHODS: We studied 104 patients, 72 women 32 men, aged 24-79 years.
      Along with neurological examination, authors studied vibration sensitivity and
      used electromyography and several scales for assessment of pain syndrome and
      other clinical presentations. RESULTS AND SONCLUSION: Clinical variants of
      peripheral neuropathy - neuropathy associated with paraproteinemia and neuropathy
      during treatment of advanced multiple myeloma with bortezomib (bortezomib-induced
      neuropathy), were singled out. An algorithm for the examination and treatment of
      patients with peripheral neuropathy was proposed.

PMID- 25591507
TI  - Amsacta moorei entomopoxvirus encodes a functional esterase (amv133) with
      protease activity.
AB  - OBJECTIVES: Lipolytic genes have been investigated in several viral genomes, and
      some of them show enzyme activity which can be used for various functions
      including the production of DNA replication metabolites, rescue from endosomes,
      and membrane fusion. Amsacta moorei entomopoxvirus (AMEV) replicates in nearly
      the entire insect body, especially in the adipose tissue. One of the open reading
      frames (ORFs) in the AMEV genome, amv133, encodes a putative lipase enzyme. In
      this study, we therefore investigate the enzyme activity of amv133. METHODS:
      amv133 was aligned with known lipase genes and their homologs in
      entomopoxviruses. Expressed proteins were partially purified and assayed for
      lipase, esterase and protease. RESULTS: We found that amv133 contains all the
      domains required for a functional lipase enzyme and that it shows a significant
      similarity with homologs in other entomopoxviruses. Since there is a similarity
      of the catalytic triad between lipases and serine proteases, we also investigated
      the protease activity of amv133. Lipase, esterase and protease assays showed that
      amv133 encodes a functional esterase enzyme with protease activity. CONCLUSION:
      The current data show that amv133 is a conserved gene in all entomopoxvirus
      genomes sequenced so far and might contribute greatly to degrading the lipids or
      proteins and hence improve the virus infection.

PMID- 25591505
TI  - Virological response after 6 week triple-drug regimens for hepatitis C: a proof
      of-concept phase 2A cohort study.
AB  - BACKGROUND: Direct-acting antiviral drugs have a high cure rate and favourable
      tolerability for patients with hepatitis C virus (HCV). Shorter courses could
      improve affordability and adherence. Sofosbuvir and ledipasvir with ribavirin
      have high efficacy when taken for 8 weeks but not for 6 weeks. We assessed
      whether the addition of a third direct-acting antiviral drug to sofosbuvir and
      ledipasvir would allow a shorter treatment duration. METHODS: In this single
      centre, open-label, phase 2A trial, we sequentially enrolled treatment-naive
      patients with HCV genotype 1 infection into three treatment groups: 12 weeks of
      sofosbuvir and ledipasvir; 6 weeks of sofosbuvir, ledipasvir, and GS-9669; or 6
      weeks of sofosbuvir, ledipasvir, and GS-9451. Patients and investigators were not
      masked to treatment assignment. The primary endpoint was the propotion of
      patients with sustained viral response at 12 weeks after treatment completion
      (SVR12), assessed by serum HCV RNA concentrations lower than 43 IU/mL (the lower
      limit of quantification). We did an intention-to-treat analysis for the primary
      endpoint and adverse events. This study is registered with ClinicalTrials.gov,
      number NCT01805882. FINDINGS: Between Jan 11, 2013, and Dec 17, 2013, we enrolled
      60 patients, and sequentially assigned them into three groups of 20. We noted an
      SVR12 in all 20 patients (100%, 95% CI 83-100) allocated to sofosbuvir and
      ledipasvir for 12 weeks; in 19 (95%, 75-100) of the 20 patients allocated to
      sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (one patient relapsed 2 weeks
      after completion of treatment); and in 19 (95%, 75-100%) of the 20 patients
      allocated to sofosbuvir, ledipasvir, and GS-9451 for 6 weeks (one patient was
      lost to follow-up after reaching sustained viral response at 4 weeks). Most
      adverse events were mild and no patients discontinued treatment. Two serious
      adverse events occurred (pain after a post-treatment liver biopsy and vertigo),
      both unrelated to study drugs. INTERPRETATION: In this small proof-of-concept
      study, two different three-drug regimens that were given for 6 weeks resulted in
      high cure rates for HCV infection with excellent tolerability. Addition of a
      third potent direct-acting antiviral drug can reduce the duration of treatment
      required to achieve sustained viral response in patients with chronic HCV
      genotype 1 infection without cirrhosis. FUNDING: National Institute of Allergy
      and Infectious Diseases (NIAID), National Cancer Institute and Clinical Center
      Intramural Program, German Research Foundation, National Institutes of Health,
      Gilead Sciences.

PMID- 25591509
TI  - [Panic disorder and affective pathology (comorbidity aspects)].
AB  - OBJECTIVE: To analyze the correlation between signs of panic disorder and
      depressive symptoms in affective disorders. MATERIAL AND METHODS: Authors studied
      40 patients (23 men and 17 women, mean age 31.8 years) with mild and moderate
      depression comorbid with symptoms of panic disorders. RESULTS: It was singled out
      two types of the comorbidity of anxiety-depressive symptoms. The first type is
      characterized by anxiety-apathetic affect with the domination of ideational
      disorders with elements of alexithymia; panic attacks were represented by clearly
      delineated paroxysms and reduced as depressive symptoms came back; affective
      disorder had bipolar phases. The second type of comorbidity was characterized by
      the somatization and asthenic symptoms in depression structure, unstable
      functional impairment in panic paroxysms; signs of partial agoraphobia and
      unipolar type of affective disorder. The complete reduction of panic attacks
      during the remission of depressive disorder was not found as well. CONCLUSION:
      The types of comorbidity have different types of the dynamics of panic and
      depressive disorders.

PMID- 25591510
TI  - [An influence of mental disorder in the child on the parents in the context of
      differentiated approaches to psychosocial interventions on childhood psychiatry].
AB  - OBJECTIVE: To specify parent reaction to a mental disorder in the child and to
      develop differential approaches to psychosocial family interventions. MATERIAL
      AND METHODS: Authors studied parents (mostly mothers) of 140 children with
      schizophrenia spectrum disorders, 100 children with autistic disorders and 85
      children with mental retardation. Along with psychiatric examination of the
      parents, it was used psychometric scales ECI and CGSQ. RESULTS: Authors specified
      emotional and behavioral characteristics of the parents' reaction as common for
      all diseases studied as well peculiar for separated forms of mental diseases in
      children. The factors (cognitive, emotional and behavioral) determining the
      targets of differentiated therapeutic interventions were singled out. CONCLUSION:
      The stress coping strategies for parents are formulated.

PMID- 25591511
TI  - [Influence of acupuncture on cerebral hemodynamic reserve during the preoperative
      period in patients with associated brachiocephalic stenosis].
AB  - OBJECTIVE: To evaluate the possibility of acupuncture, as an element of
      preoperative preparation of the patient to carotid endarterectomy, for increasing
      the tolerance of patients with brachiocephalic stenosis to cerebral ischemia.
      MATERIAL AND METHODS: We studied 40 inpatients with low tolerance to carotid
      compression test. Ultrasound examination of brachiocephalic and intracranial
      blood flow was carried out, including carotid compression, apneic and
      hyperventilation tests. We examined 20 people from the control group before
      traditional medicinal treatment as well as after first and second therapeutic
      courses; 20 patients from the main group were tested before and after medicinal
      treatment, and after acupuncture course. RESULTS: We couldn't identify any
      significant changes in cerebral hemodynamic reserve in patients with severe
      carotid stenosis after medicinal therapy; at the same time we registered its
      reliable 2.16 fold growth after acupuncture treatment. CONCLUSION: Acupuncture
      treatment leads to cerebral hemodynamic reserve growth in most patients with
      significant brachiocephalic stenosis. The inclusion of acupuncture in therapeutic
      complex improves the quality of preoperative preparation to carotid
      endarterectomy and its tolerability.

PMID- 25591512
TI  - [Efficacy of the combination drug vasobral in chronic vascular encephalopathy].
AB  - OBJECTIVE: Despite the high prevalence of chronic vascular encephalopathy, its
      diagnosis and treatment remain understudied. This observational multicenter trial
      assessed the efficacy and safety of vasobral in patients with cerebral ischemia.
      MATERIAL AND METHODS: The open observational study was carried out in 37 centers
      in 11 Russian cities and included 300 patients with confirmed diagnosis of
      chronic vascular encephalopathy, stages 1 and 2, without dementia. The patients
      received 1 tablet (4 mg alpha-dihydroergocryptine and 40 mg caffeine) 2 times a
      day during 3 months. RESULTS AND CONCLUSION: There was an improvement of
      cognitive and affective status as well as quality of life and a decrease of
      subjective signs of chronic vascular encephalopathy. Vasobral did not cause
      significant fluctuations of arterial pressure and was safe for patients with
      chronic vascular encephalopathy and arterial hypertension.

PMID- 25591513
TI  - [The possibilities of increase of efficacy of rehabilitation of stroke patients
      with neglect syndrome].
AB  - OBJECTIVE: To evaluate different treatment schemes for post stroke patients with
      neglect syndrome (NS). MATERIAL AND METHODS: We studied management rules for
      patients with NS and the effect of ceraxon (citicoline) on the functional
      rehabilitation and removal of the neglect syndrome. We analyzed treatment results
      of 120 stroke patients. The functional rehabilitation was followed up using
      Barthel, Lindmark and Merton and Sutton scales, cognitive functions were assessed
      with the MMSE scale and the battery of frontal dysfunction, psychoemotional
      condition with the Beck Depression Questionnaire. Moreover, treatment efficacy
      has been evaluated by the absence of NS signs. RESULTS AND CONCLUSION:
      Maintenance of management rules and use of ceraxon improved the functional
      rehabilitation of stroke patients with NS.

PMID- 25591514
TI  - [The use of stalevo in the treatment of patients with Parkinson's disease].
AB  - OBJECTIVE: To assess the efficacy and tolerability of the three component drug
      stalevo in the treatment of patients with Parkinson's disease (PD). MATERIAL AND
      METHODS: We analyzed the experience of using the antiparkinsonian drug stalevo
      (levodopa/carbidopa/entacapone) in the treatment of acute stages of PD and
      elderly patients with restricted possibilities of using other antiparkinsonian
      drugs. The study included 47 patients. A clinical example is presented. RESULTS
      AND SONCLUSION: Stalevo increased motor and daily activities, reduced the
      severity of basic symptoms of PD and improved quality of life of the patients.

PMID- 25591515
TI  - [Post-stroke spasticity of the lower limb: a comprehensive rehabilitation of
      patients with the use of botulinum toxin (onabotulinumtoxin A)].
AB  - OBJECTIVE: To examine the efficacy of onabotulinumtoxin A (Botox) in the complex
      rehabilitation of patients with post-stroke spasticity of the leg in the early
      rehabilitation period of stroke. MATERIALS AND METHODS: The study group comprised
      31 patients in the early recovery period after stroke with the presence of equino
      varus deformity of the foot with spasticity grade 3 or more (MAS). All patients
      received injections of onabotulinumtoxin A (Botox) in a total dose 400 ED as part
      of a comprehensive rehabilitation program. Dynamics of neurological status,
      spasticity, pain, function of walking and everyday activity was evaluated.
      RESULTS AND SONCLUSION: The high efficacy of botulinum neurotoxin type A was
      demonstrated. The drug reduced the severity of spasticity and discomfort in the
      leg and foot; promoted independent movement and increased walking speed of the
      patient.

PMID- 25591516
TI  - [Efficacy of antioxidant energocorrestion in brain infarction (results of a
      multicenter randomized trial)].
AB  - OBJECTIVE: To determine the optimal duration of energy corrective treatment of
      ischemic stroke (II) with cytoflavin or ascorbic acid. MATERIAL AND METHODS: A
      multicenter randomized clinical trial included 185 patients, aged 40-75 years.
      Patients were randomized into 3 groups: the control group (n=64) received
      ascorbic acid; cytoflavin group 1 (n=72) was treated for 10 days and cytoflavin
      group 2 (n=49) for 20 days. In all groups, mean NIHSS score was 13, 42.2% of
      patients scored >=14 and on admission, 42.2% of patients had consciousness
      impairment of different severity. RESULTS: Cytoflavin treatment was more
      efficient than ascorbic acid that can be explained by different pharmacologic
      mechanisms. Treatment with cytoflavin for 10 days resulted in a significant
      decrease of ischemia zone volume by 25.2%, treatment with cytoflavin for 20 days 
      by 29.0%, which was associated with better outcomes in neurologic and functional
      status. Ascorbic acid demonstrated no effect on morphologic parameters. Prolonged
      treatment with cytoflavin in critically ill patients led to significant
      improvement in clinical and morphologic variables compared to the 10-day course.
      In patients with less severe condition comparable results were obtained.
      CONCLUSION: Our data justify the need for personalized integrated antioxidant and
      energy correction therapy.

PMID- 25591517
TI  - [Comorbidity of tics and stuttering].
AB  - OBJECTIVE: To determine the clinical presentations of stuttering in children with
      tics treated with noofen. MATERIAL AND METHODS: Authors examined 181 children
      with tics, aged 7-13. Stuttering was identified in 23.2% of cases. Thirty
      children with tics and comorbid stuttering received noofen. RESULTS AND
      SONCLUSION: The prevalence of stuttering in children with tics was significantly
      higher than in the population. Stuttering was significantly more frequent in
      children with transient tics than chronic tics. Neurotic stuttering was recorded
      more frequently. The high efficacy of noofen was shown; the decrease in ticks was
      obtained in 80% of cases, the reduction of stuttering in 66.7% of cases. The data
      of clinical, psychological and neurophysiological studies, confirming the
      improvement of patients after treatment, are presented.

PMID- 25591518
TI  - [New possibilities of pharmacological treatment of adult epilepsy].
AB  - OBJECTIVE: To study an effect of cortexin on epilepsy course and
      electroencephalographic pattern in stopping the symptoms concomitant to epilepsy.
      MATERIAL AND METHODS: A study included 64 patients with epilepsy (22 men and 42
      women, aged from 20 to 85 years). Along with standard treatment, the patients
      received cortexin (three 10-day courses during 12 months intramuscular in dose 10
      mg daily). RESULTS AND CONCLUSION: There were the significant decrease in the
      frequency of seizures and the absence of failure of remission, the positive
      dynamics of electroencephalographic pattern as well as stopping of such symptoms
      as headache, non-systemic vertigo, asthenia, cognitive impairment, anxiety and
      depression, arterial hypertension.

PMID- 25591519
TI  - [The use of mood stabilizers in preventive treatment of patients with
      schizoaffective disorders].
AB  - OBJECTIVE: To study an effect of combination therapy consisting of mood
      stabilizers on the quality of remission in patients with schizoaffective
      disorders. MATERIAL AND METHODS: Authors examined 56 outpatients with ICD-10
      diagnosis of schizoaffective disorder (F25). Patients in remission received anti
      relapse therapy with antipsychotics and were not treated with mood stabilizers
      for at least two years, and then they received a combined anti-relapse therapy,
      including both antipsychotics and mood stabilizers. RESULTS AND CONCLUSION: The
      combined use of pharmacotherapy creates a better remission. No statistically
      significant differences in the effect of different groups of mood stabilizers on
      the average duration of remission are identified. The inclusion of mood
      stabilizers in the scheme of preventive treatment has no effect on the average
      duration of subsequent hospitalization. Mood stabilizers are effective in the
      prevention of suicidal behavior in patients with schizoaffective disorder, they
      reduce the risk of disability in patients with schizoaffective disorder and
      increase compliance.

PMID- 25591520
TI  - [The use of different doses of botulotoxin A in the treatment of early arm
      poststroke spasticity].
AB  - OBJECTIVE: Local injections of botulinum toxin type A (BTA) are currently used in
      treatment of poststroke spasticity. We assessed the efficacy of botulinum
      treatment using different doses of BTA. MATERIAL AND METHODS: We studied 68
      patients with early arm poststroke spasticity in the acute and early recovery
      stages of stroke (up to 3 months from disease onset), mean age of the patients
      was 60,3+/-11,4 years. RESULTS AND CONCLUSION: BTA used in half dose of the mean
      recommended dose reduced motor disorders thus promoting the prevention of severe
      spasticity, formation of early contractures and relief of painful shoulder
      syndrome.

PMID- 25591521
TI  - [An impact of neuroprotective therapy on blood rheological and
      morphodensitometric parameters in patients with chronic cerebral ischemia].
AB  - OBJECTIVE: To explore the dynamics of aggregation of platelets and erythrocytes,
      their deformity and computed morphodensitometric parameters in patients with
      chronic cerebral ischemia, stages I and II, treated with cerebrolysin. MATERIAL
      AND METHODS: We examined 300 patients, including 87 men and 213 women, aged from
      30 to 55 years. Patients were randomized by disease stage and treatment (standard
      treatment with or without cerebrolysin). The dynamics of neurological and
      emotional status as well as cognitive functions and results of laboratory studies
      were assessed. RESULTS AND CONCLUSION: Along with the total positive effect of
      cerebrolysin on the clinical picture, additional mechanisms of its action
      (antiaggregant, antihypoxic and membranotropic) improved the erythrocyte
      morphodensitometric parameters, hemostatic, hemorheological and blood gas
      transport characteristics, in particular on the microcirculatory level.

PMID- 25591522
TI  - [Treatment of cognitive and psychoemotional disorders in poststroke patients].
AB  - OBJECTIVE: To evaluate the efficacy of the drug sermion (nicergoline) in
      poststroke patients with cognitive and psychoemotional disorders. MATERIAL AND
      METHODS: The study included 880 patients, including 440 patients with depression
      and 440 with cognitive impairment, mean age of patients was 69,6 years. The
      restoration of cognitive functions was followed up using MMSE scales,
      psychoemotional condition was assessed with the Beck Depression Questionnaire and
      the Wakefield Depression Scale. RESULTS AND CONCLUSION: The efficacy of sermion
      has been demonstrated. Application of this drug in the rehabilitation of stroke
      patients significantly contributes to the improvement of cognitive functions and
      normalization of mental and emotional state of patients.

PMID- 25591523
TI  - [Current possibilities of stabilometric diagnosis of migraine-associated
      vertigo].
AB  - OBJECTIVE: To study characteristics of migraine-associated vertigo using a
      specially-developed complex program of stabilometry. MATERIAL AND METHODS: We
      examined 56 patients with vestibular migraine and 56 healthy controls. We used a
      set of tests informative for verification of the pathology of the vestibular
      system (examination in the Romberg position with opened and closed eyes,
      optic/kinetic test, test with turns and inclinations of head, tandem test).
      RESULTS AND CONCLUSION: Based on significant differences in stabilometric
      parameters that are characteristic of the main group, we concluded that computer
      stabilometry can be used for diagnosis of migraine-associated vertigo.

PMID- 25591524
TI  - [The study of biochemical autoregulation of blood flow in the vascular basin of
      the inner carotid artery in premature children].
AB  - OBJECTIVE: Despite the importance of blood flow regulation (BFR) in cerebral
      vessels, in particular, during organism development, there is no studies in
      children in the first weeks of life. We studied biochemical autoregulation of
      blood flow in infants born at 24-25 weeks of gestation. MATERIAL AND METHODS:
      Eighteen infants with body mass 763+/-138 g were included in the study. RESULTS:
      There was a high frequency of intraventricular hemorrhages (77%, 14 infants),
      including those of III stage (50%) with ventriculomegalia (9 infants). Cystic
      periventricular leukomalacia developed in 50% (9 infants). Retinopathy of
      premature children with localization in the posterior pole of eyeball developed
      in 100% of cases. Results of capillary blood gas analysis (pO2, pCO2 and
      parameters of resistance index of anterior cerebral artery measured using Doppler
      ultrasound) were studied from 25 to 30 weeks of gestation. In the first weeks of
      life, spastic character of blood flow in the anterior cerebral artery against the
      background of hypoxemia and relative hypocapnia was found. No data on the
      hyperoxic autoregulation of blood flow was obtained. The hypercapnic mechanism of
      autoregulation had developed earlier and emerged from the 28th week of gestation.
      Conclusion. The dramatic increase in hypercapnia leads to the blood inflow to
      tissues and finally to the early development of retinopathy, periventricular
      leukomalacia and intraventricular hemorrhages.

PMID- 25591525
TI  - [Predictive value of blood serum cytokines in patients with supratentorial
      meningiomas].
AB  - OBJECTIVE: To establish a predictive role of blood serum cytokines and their
      effect on a clinical picture of patients with supratentorial meningiomas.
      MATERIAL AND METHODS: Levels of interleukin-4, interleukin-6 and gamma-interferon
      were measured in 26 patients using immunoenzymatic method. Assessment of a
      predictive role of cytokine levels was carried out by a method of the analysis of
      multidimensional data and cluster analysis on the basis of Kokhonen's neural
      network. Correlation between cytokine level and scores on the Karnovsky scale at
      discharge from hospital was used as an indicator of treatment efficacy. RESULTS:
      The changes in interleukin-4 level had no impact on a clinical condition of
      patients while the fluctuations of blood serum played a significant role.
      CONCLUSION: To predict clinical condition and timely treatment correction in
      patients with supratentorial meningiomas, monitoring of interleukin-6 and gamma
      interferon levels is needed.

PMID- 25591526
TI  - [Possibilities of the use of immunological indicators for the assessment of the
      risk of manifestation of endogenous psychoses in patients with nonpsychotic
      disorders of the juvenile age].
AB  - OBJECTIVE: To study parameters of innate and adaptive immunity in the blood serum
      of patients with nonpsychotic mental disorders and to classify them by risk of
      psychosis manifestation. MATERIAL AND METHODS: Authors studied 49 male patients,
      aged from 16 to 25 years, with nonpsychotic mental disorders corresponded to the
      premanifest stage of endogenous psychosis. The activity of leukocyte elastase
      (LE), functional activity of alpha-1-proteinase inhibitor (alpha1-PI) and the
      level of autoantibodies (aAB) to S-100 and basic myelin protein were measured.
      RESULTS: A significant increase in LE and alpha1-PI was found in patients
      compared to controls (p<0.001). The level of aAB to neuroantigens was similar in
      patients and controls. The increase in LE activity was positively correlated with
      HAM-D depressive symptoms and SOPS total scores (r=0.47, p=0.02). Correlations
      between alpha1-PI activity and scores on SOPS positive subscale (r= -0.61,
      p=0.002) and SOPS total scores (r= -0.43, p=0.04) were identified. After
      treatment, the improvement of patient's state assessed by SOPS and HAM-D was
      correlated with the decrease in LE activity in 80% (p<0.01). The further increase
      of LE activity in 20% may be considered as an indicator of low quality remission
      and risk of psychosis manifestation. CONCLUSION: Patients with nonpsychotic
      mental disorders with higher levels of inflammation markers may be attributed to
      high risk group.

PMID- 25591527
TI  - [The application of long-acting injectable antipsychotics in clinical practice
      (overcoming of obstacles)].
AB  - OBJECTIVE: To explore the patients' attitudes towards the long-acting injectable
      antipsychotics. MATERIAL AND METHODS: Authors surveyed 164 psychotic outpatients.
      RESULTS: Psychiatrists suggested long-acting injectable antipsychotics to 59.7%
      of the patients. Among these patients, 64.3% agreed with and 35.5% rejected this
      treatment. The fear of side-effects (57.1%) and the need of regular visits to
      psychiatrists (48.6%) were the main reasons of the rejection. The advantages of
      long-acting injectable antipsychotics, as viewed by the patients, and some
      obstacles to their use were determined. CONCLUSION: Psychoeducational and
      psychoterapeutical programs for patients and psychiatrists are needed.

PMID- 25591528
TI  - [Two cases of a proximal spinal muscular atrophy (Werdnig-Hoffmann's disease) in
      one family].
AB  - A short review of literature data on the pathogenesis and clinical presentations
      of spinal muscular atrophies is provided. We report two cases of Werdnig
      Hoffmann's disease in one family and present a diagnostic search strategy which
      allows the ordinary neurologist to distinguish this pathology. 

PMID- 25591529
TI  - [Effects of ecological characteristics of place of residence on the incidence,
      prevalence and risk of multiple sclerosis in the Republic North Ossetia -
      Alania].
AB  - Objective. To study the relationship between characteristics of place of
      residence and epidemiological indicators of multiple sclerosis (MS) in the
      Republic North Ossetia - Alania. Material and methods. We present the data on the
      effects of environmental characteristics of place of residence on the incidence,
      prevalence and risk of MS. Data of 110 MS patients and matched controls have been
      analyzed. Results. Ecological characteristics of place of residence of MS
      patients differ significantly from those of controls. The prevalence and
      incidence of MS increase in patients who have moved from presumably pollution
      free areas to the places with high population density and plant facilities.
      Conclusion. MS is thought to be a disease caused by the interaction of genetic
      susceptibility and environmental factors. Risk factors are intoxication with
      heavy metal and chemical compounds and living in environmentally disadvantaged
      areas. 

PMID- 25591530
TI  - [An analysis of an effect of infectious diseases and diet factors on the risk of
      multiple sclerosis in the population of the Republic North Ossetia - Alania].
AB  - Objective. To carry out the first in the Republic North Ossetia - Alania clinical
      epidemiological study of environmental risk factors for multiple sclerosis (MS)
      in the indigenous population. Material and methods. We have analyzed results of a
      questionnaire survey of 110 patients with MS and 110 matched controls. Results.
      We have identified statistically significant differences between the type of diet
      of MS patients and controls in different age periods, as well as the most
      significant infectious risk factors for MS. Conclusion. MS is a chronic
      autoimmune disease caused by the interaction of genetic and environmental
      factors. Among the environmental factors, infectious diseases and type of diet
      play the most important role. 

PMID- 25591531
TI  - [Pregnancy and experimental autoimmune encephalomyelitis induced in different
      terms of gestation period].
AB  - Objective. To investigate the features of the clinical course of experimental
      demyelinating pathology as a model of multiple sclerosis in rats in different
      trimesters of pregnancy. Material and methods. We used 48 nonlinear white female
      rats to study an effect of pregnancy on susceptibility to and clinical features
      of demyelinating pathology. Results and sonclusion. Severity of disease was shown
      to be a priority risk factor of pregnancy, which is realized depending on the
      period of gestation. An increase of representation and aggravation of the
      reproductive pathology during modeling of multiple sclerosis in II trimester
      indicates a risk of relapse in the late periods of reproduction cycle, derogates
      the idea about total retentive influence of pregnancy on the development of
      demyelinating events. 

PMID- 25591532
TI  - [Brain-derived and ciliary neurotrophic factors in patients with multiple
      sclerosis].
AB  - Objective. To study serum concentrations of BDNF and CNTF in patients with
      multiple sclerosis (MS) and compare them to clinical characteristics of MS.
      Material and methods. We examined 43 patients with confirmed diagnosis of MS
      according to McDonald's criteria with remitting type of disease course. Patients
      were in a stable condition and did not receive hormone treatment during the last
      30 days. Serum concentrations of BDNF and CNTF were measured using ELISA.
      Results. Mean serum BDNF concentration was 7.9 (5.21; 14.7) ng/ml that was
      significantly lower (p=0.0001) compared to control values and was correlated with
      depression severity (r= -0.31, p=0.04) and physical asthenia (r= -0.32, p=0.04).
      CNTF concentration was 69.9 (31.2; 123.3) pg/ml (CNTF was not found in healthy
      people) and was correlated with the results of cognitive function assessment (the
      PASAT test) (r= -0.30, p=0.046). Conclusion. The difference in BDNF and CNTF
      serum concentrations between MS patients and healthy people and correlations with
      some clinical characteristics of MS provide evidence for the involvement of these
      factors in MS pathogenesis. 

PMID- 25591533
TI  - [No support for the hypothesis of chronic cerebrospinal venous insufficiency in
      multiple sclerosis].
AB  - Objective. To evaluate the jugular veins (IJV) using duplex sonography in
      patients with multiple sclerosis (MS). Material and methods. The study included
      21 MS patients with different disease course, degree of disability and disease
      duration. A control group consisted of 8 healthy volunteers. Results. IJV changes
      that meet the CCSVI criteria have not been found. These findings are consistent
      with the results of recently published large studies. Possible reasons of non
      confirmation of this hypothesis are discussed. Conclusion. Currently vascular
      intervention in MS is not recommended. 

PMID- 25591534
TI  - [Cortical atrophy in multiple sclerosis].
AB  - Objective. To identify clear patterns of the cerebral cortex atrophy in multiple
      sclerosis that may provide valuable information for the development of additional
      paraclinical methods of stages and variants of MS objectification and
      verification and used for assessing treatment efficacy. Material and methods. The
      results of morphometric data analysis of 117 patients with different variants of
      MS and 25 healthy volunteers are presented. The original algorithm for
      postprocessing MRI images was used. Age, disease duration, type of disease, FS
      and EDSS scores, morphometric results were the source parameters for the
      statistical analysis. Results. The correlation analysis showed that the total
      cortex volume was in inverse correlation with EDSS score, pyramidal and
      cerebellar dysfunction, but not with disease duration. An analysis of regional
      changes in 43 bilateral regions of interest (ROI) demonstrated similar results in
      7 ROIs in the left (dominant) hemisphere and in 4 ROIs in the right hemisphere.
      ANOVA revealed atrophic changes in 20 ROIs bilaterally. Deficit of certain
      functional systems was accompanied by the atrophy of various functional cortex
      regions. ANOVA of the regional cortical atrophy in groups with varying disease
      severity showed the presence of significant changes in patients with moderate to
      severe disability. Duration and type of MS were not predictive for development of
      atrophy, with the exception of the precuneus bilaterally, the right paracentral
      lobule and right posterior cingulate gyrus. Conclusion. Regional cortical atrophy
      is detected in the earliest stages of the disease and increases as the disease
      progresses. Inconsistency of data across studies can be explained by the lack of
      generally accepted morphometric standards and pathogenetic heterogeneity of MS.
      Regional cortical atrophy may be considered as a sensitive neuroradiological
      biomarker for MS. 

PMID- 25591535
TI  - [Atrophy of the central nervous system in multiple sclerosis: MRI-morphometry
      results].
AB  - Nowadays the majority of multiple sclerosis (MS) research pays attention to the
      neurodegenerative component, using a magnetic resonance imaging voxel-based
      morphometry for its assessment. Cerebral atrophy occurs in the earliest stages of
      MS in different clinical phenotypes and progresses three times faster than in
      healthy individuals. WM atrophy involved almost all brain regions, but is less
      pronounced than GM loss. GM atrophy has distinct patterns of regional
      distribution in patients with different clinical phenotypes, more extensive in
      the progressive than in the relapsing disease phenotypes. Deep GM atrophy is
      demonstrated to correlate with WM lesion as well as cortical atrophy. GM atrophy
      shows significant correlations with T2 lesion volume, cognitive function and
      measures of physical disability. In addition to cerebral loss, MS patients
      frequently develop spinal cord atrophy, which also correlates with clinical
      impairment. However, the order of GM and WM involvement still remains unclear.
      And further research of atrophy MRI-predictors is needed in order to monitor
      clinical course of MS. 

PMID- 25591536
TI  - [The relationship between cognitive impairment and localization of white matter
      lesions in patients with multiple sclerosis].
AB  - Objective. To study a role of parenchymal white matter lesions and lesions of the
      white matter underlying the cortical grey matter in cognitive impairment in
      patients with multiple sclerosis (MS). Material and methods. We examined 33
      patients with clinically definite RRMS in clinical remission. Cognitive
      performance was assessed with neuropsychological and psychometric tests. MRI (1.5
      tesla) was used to assess volume and localization of focal demyelination in the
      cerebral cortex. Results. The volume of juxtacortical brain lesions in the white
      matter had a negative effect on the correct performance on neuropsychological
      tests. The volume of parenchymal white matter lesions had a negative effect on
      the speed of task performance. Conclusion. The results suggest that MS patients
      had multiple cognitive impairments. 

PMID- 25591537
TI  - [A case of anti-NMDA-receptor encephalitis].
AB  - A clinical case of encephalitis caused by antibodies to NMDA-receptors is
      presented. This rare pathology is characterized by severe cognitive impairment
      and needs careful differential diagnosis. 

PMID- 25591538
TI  - [Cellular composition of Peyer's patches and peripheral lymph nodes in
      experimental allergic encephalomyelitis during fingolimod therapy].
AB  - Objective. To determine the pattern of lymphocyte composition changes in Peyer's
      patches and peripheral lymph nodes in the development of experimental allergic
      encephalomyelitis (EAE) in mice without treatment and during fingolimod therapy.
      Material and methods. The research was performed on 40 inbred mice C57BI/6 which
      were stratified into two groups: mice with EAE of group 1 received no treatment,
      mice with EAE of group 2 were treated with fingolimod. Results. The development
      of EAE was accompanied by relative density increasing of lymphocytes, CD4, CD8
      cells in Peyer's patches and peripheral lymph nodes that indicated the lymphoid
      tissue's active systemic response to EAE development. The fingolimod treatment of
      laboratory animals with EAE resulted in a more significant and prolonged increase
      in the relative density of lymphocytes, CD4 and especially CD8 cells in the
      lymphoid formations and also the development of less severe neurological symptoms
      that confirmed the efficacy of therapy. Conclusion. The intestinal lymphoid
      tissue may be actively involved in the development of autoimmune demyelinating
      process in the central nervous system. 

PMID- 25591539
TI  - [The first Russian experience of using natalizumab in the treatment of relapsing
      remitting multiple sclerosis in children].

PMID- 25591540
TI  - [Asthenia, emotional disorders and quality of life of patients with multiple
      sclerosis].
AB  - Objective. The evaluation of the dynamics of asthenia, chronic fatigue syndrome,
      emotional disorders and quality of life of patients with multiple sclerosis (MS)
      and to explore the possibility of using idebenon (noben) in treatment of these
      impairments. Material and methods. We studied 35 patients, 18 men and 17 women,
      with MS (mean age 36.4+/-8.86 years, mean disease duration 10.33+/-6.07 years);
      83% of patients had remitting type and others - secondary progressive type. Along
      with neurological examination, we used the Modified Fatigue Impact Scale (MFIS
      21), the Hospital Anxiety and Depression Scale and a quality of life
      questionnaire (EQ5D). Patients had marked asthenia and chronic fatigue at
      baseline. The old age of the patients and duration of MS and its severity
      according to EDSS predicted the higher levels of asthenia, chronic fatigue and
      anxiety with depression and lower quality of life on EQ5D. All patients received
      noben in dosage 90 mg daily (30 mg 3 times a day) during 6 months. Results and
      conclusion. Idebenon (noben) reduced the severity of chronic fatigue syndrome,
      asthenia and depression in MS patients. The dose used in the study may be
      regarded as the optimal dose that provides best efficacy with minimal side
      effects. 

PMID- 25591541
TI  - Identification of human papillomaviruses from formalin-fixed, paraffin-embedded
      pre-cancer and invasive cervical cancer specimens in Zambia: a cross-sectional
      study.
AB  - BACKGROUND: The most common human papillomavirus (HPV) genotypes isolated from
      cervical cancer in select African countries are HPV-16, HPV-18, HPV-35, and HPV
      45, but the most common genotypes in Zambia are unknown. The overall objective of
      this study was to assess the potential impact of current HPV vaccines in
      preventing cervical cancer in Zambia, by determining the combined prevalence of
      HPV-16 and/or HPV-18 in invasive cervical cancer (ICC) and high-grade pre-cancer
      [cervical intraepithelial neoplasia 2 or 3 (CIN2/3)] cases. FINDINGS: We compared
      DNA extraction techniques to determine which assay performs well in the Zambian
      context, where unbuffered formalin is used to fix specimens. We then tested
      specimens with the Abbott RealTime High-Risk HPV test to estimate the prevalence
      of HPV-16/18 in formalin-fixed, paraffin-embedded ICC and CIN2/3 specimens. DNA
      extraction using heat (without xylene) was more successful than xylene-based
      extraction. Over 80% of specimens tested using heat extraction and the Abbott
      RealTime HPV test were positive for HPV. HPV-16 and/or HPV-18 were identified in
      65/93 (69.9%) ICC specimens positive for HPV and in 38/65 (58.5%) CIN2/3
      specimens positive for HPV. CONCLUSIONS: To our knowledge this is the first
      report to identify HPV genotypes in cervical cancers in Zambia. A combined HPV
      16/18 prevalence of 69.9% in ICC specimens suggests that current vaccines will be
      highly protective against cervical cancer in Zambia.

PMID- 25591542
TI  - Brain amyloid-beta fragment signatures in pathological ageing and Alzheimer's
      disease by hybrid immunoprecipitation mass spectrometry.
AB  - BACKGROUND: Senile plaques in Alzheimer's disease (AD) are composed of amyloid
      beta (Abeta), especially N-truncated forms including Abeta4-42. These are thought
      to be neurotoxic. However, individuals may live for decades with biomarker
      evidence of cerebral beta-amyloidosis (positive amyloid PET imaging and/or low
      cerebrospinal fluid levels of the 42 amino acid form of Abeta) without cognitive
      impairment. This condition may be termed pathological ageing (PA). OBJECTIVE: To
      investigate whether there is a difference in the cerebral Abeta fragment pattern
      in brain specimens from non-demented (PA) and demented (AD) individuals
      expressing the full neuropathological triad of AD (senile plaques,
      neurofibrillary tangles and neurodegeneration). METHODS: We extracted Abeta using
      formic acid and hybrid (6E10 and 4G8) immunoprecipitation from fresh-frozen
      temporal cortex tissue of 6 elderly individuals (mean age +/- SD: 89 +/- 3.5
      years) with PA and 10 patients with AD (mean age +/- SD: 72 +/- 8.5 years). The
      full spectrum of Abeta peptides was determined by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry. RESULTS: AD patients had
      generally more N-terminally truncated and pyroglutamate-modified Abeta than PA
      patients, whereas PA patients had on average more Abeta1-40 than AD patients.
      CONCLUSION: Senile plaques in AD may have an Abeta fragment composition distinct
      from PA with more N-terminally and pyroglutamate-modified Abeta peptides that may
      be linked to neurotoxicity.

PMID- 25591543
TI  - Peptide therapeutics: targeting the undruggable space.
AB  - Rapid advancements in genomics have brought a better understanding of molecular
      mechanisms for various pathologies and identified a number of highly attractive
      target classes. Some of these targets include intracellular protein-protein
      interactions (PPIs), which control many essential biological pathways. Their
      surfaces are part of a diverse and unexplored biological space, where traditional
      small molecule scaffolds are not always successful. While large biologics can
      effectively modulate PPIs in the extracellular region, their limitation in
      crossing the cellular membrane leaves intracellular protein targets outside of
      their reach. There is a growing need in the pharmaceutical field to push the
      boundaries of traditional drug design and discover innovative molecules that are
      able to modulate key biological pathways by inhibiting intracellular PPIs.
      Peptides are one of the most promising classes of molecules that could deliver
      such therapeutics in the near future. In this review, we describe technological
      advancements and emerging chemical approaches for stabilizing active peptide
      conformations, including stapling, hydrogen bond surrogates, beta-hairpin
      mimetics, grafting on stable scaffolds, and macrocyclization. These design
      strategies carry the promise of opening the doors for peptide therapeutics to
      reach the currently "undruggable" space. 

PMID- 25591544
TI  - The singlet-oxygen-sensitized delayed fluorescence in mammalian cells: a time
      resolved microscopy approach.
AB  - The present work provides a proof-of-concept that the singlet oxygen-sensitized
      delayed fluorescence (SOSDF) can be detected from individual living mammalian
      cells in a time-resolved microscopy experiment. To this end, 3T3 mouse
      fibroblasts incubated with 100 MUM TPPS4 or TMPyP were used and the microsecond
      kinetics of the delayed fluorescence (DF) were recorded. The analysis revealed
      that SOSDF is the major component of the overall DF signal. The microscopy
      approach enables precise control of experimental conditions - the DF kinetics are
      clearly influenced by the presence of the (1)O2 quencher (sodium azide), H2O/D2O
      exchange, and the oxygen concentration. Analysis of SOSDF kinetics, which was
      reconstructed as a difference DF kinetics between the unquenched and the NaN3
      quenched samples, provides a cellular (1)O2 lifetime of tauDelta = 1-2 MUs and a
      TPPS4 triplet lifetime of tauT = 22 +/- 5 MUs in agreement with previously
      published values. The short SOSDF acquisition times, typically in the range of
      tens of seconds, enable us to study the dynamic cellular processes. It is shown
      that SOSDF lifetimes increase during PDT-like treatment, which may provide
      valuable information about changes of the intracellular microenvironment. SOSDF
      is proposed and evaluated as an alternative tool for (1)O2 detection in
      biological systems. 

PMID- 25591545
TI  - Changes in dental plaque microbial richness and oral behavioral habits during
      caries development in young Chinese children.
AB  - OBJECTIVE: To detect changes in the microbial richness of dental plaque and oral
      behaviors during caries development in young Chinese children. METHODS:
      Supragingival plaque samples and a survey of oral behaviors of 130 children aged
      3 at baseline were analyzed at 6 months and 12 months. Total DNA was isolated
      from all samples and PCR-denaturing gradient gel electrophoresis analysis was
      conducted. RESULTS: In the follow-up, 44 children had caries or cavity fillings
      at 6 months, a further 28 children had caries or cavity fillings at 12 months.
      The other 58 children remained caries-free at 12 months. According to the changes
      in caries status at the 12-month follow-up, all participants were divided into
      three groups: caries-free, caries at 6 months and caries at 12 months. The
      changes in oral behaviors during the 12-month follow-up were not significantly
      different in the three groups. The frequency of eating sweets and eating sweets
      before sleeping was significantly different among the three groups at baseline.
      At baseline, the average detectable bands of caries in the 12-month caries group
      were similar to those of the caries-free group; both of them were higher than
      that of the 6-month caries group. At 6 months, the average detectable bands of
      the 12-month caries group were significantly lower than that of the caries-free
      group although the children of the 12-month caries group were caries-free at that
      time. CONCLUSIONS: For young Chinese children, the high frequency of eating
      sweets and eating sweets before sleeping are risk factors of caries onset, and
      the decrease in microbial richness could occur 6 months before the onset of
      caries.

PMID- 25591546
TI  - Evaluation of toxicity to triclosan in rats following 28 days of exposure to
      aerosol inhalation.
AB  - The present study was conducted to investigate the potential subchronic toxicity
      of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation.
      Four groups of six rats of each sex were exposed to TCS-containing aerosols by
      nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over
      a 28-day period. During the study period, clinical signs, mortality, body weight,
      food consumption, ophthalmoscopy, hematology, serum biochemistry, gross
      pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of
      both sexes exhibited an increase in the incidence of postdosing salivation and a
      decrease in body weight. Histopathological alterations were found in the nasal
      septum and larynx. There were no treatment-related effects in rats of either sex
      at ?0.13 mg/L. Under the present experimental conditions, the target organs in
      rats were determined to be the nasal cavity and larynx. The no-observed-adverse
      effect concentration in rats was determined to be 0.13 mg/L.

PMID- 25591547
TI  - Causes of drug shortages in the legal pharmaceutical framework.
AB  - INTRODUCTION: Different causes of drug shortages can be linked to the
      pharmaceutical legal framework, such as: parallel trade, quality requirements,
      economic decisions to suspend or cease production, etc. However until now no in
      depth study of the different regulations affecting drug shortages is available.
      The aim of this paper is to provide an analysis of relevant legal and regulatory
      measures in the European pharmaceutical framework which influence drug shortages.
      METHODS: Different European and national legislations governing human medicinal
      products were analyzed (e.g. Directive 2001/83/EC and Directive 2011/62/EU),
      supplemented with literature studies. RESULTS: For patented drugs, external price
      referencing may encompass the largest impact on drug shortages. For generic
      medicines, internal or external reference pricing, tendering as well as price
      capping may affect drug shortages. Manufacturing/quality requirements also
      contribute to drug shortages, since non-compliance leads to recalls. The
      influence of parallel trade on drug shortages is still rather disputable.
      CONCLUSION: Price and quality regulations are both important causes of drug
      shortages or drug unavailability. It can be concluded that there is room for
      improvement in the pharmaceutical legal framework within the lines drawn by the
      EU to mitigate drug shortages.

PMID- 25591548
TI  - Overexpression of interleukin-18 protein reduces viability and induces apoptosis
      of tongue squamous cell carcinoma cells by activation of glycogen synthase kinase
      3beta signaling.
AB  - The aim of this study was to investigate the effects of interleukin-18 (IL-18)
      expression on regulating the viability and apoptosis of tongue squamous cell
      carcinoma (TSCC) cells in vitro and examine the underlying molecular events.
      Human IL-18 cDNA was cloned into the vector pcDNA3.1 (+) and transfected into CRL
      1623TM cells. Quantitative reverse transcription-PCR (RT-qPCR), western blot
      analysis, immunofluorescence, cell viability MTT assay, flow cytometric Annexin
      V/propidium iodide (PI), Giemsa staining, and caspase-3 activity assay were
      performed. The data showed that overexpression of IL-18 protein reduced TSCC cell
      viability by inducing apoptosis. Compared with cells transfected with the control
      vector, IL-18 expression activated caspase-3, -7, and -9 by inducing their
      cleavage and increased the expression of interferon (IFN)-gamma and cytochrome c
      mRNA, but reduced cyclin D1 and A1 expression in TSCC cells. IL-18 expression
      upregulated the expression and phosphorylation of glycogen synthase kinase (GSK)
      3beta protein in CRL1623 cells, whereas the selective GSK-3beta inhibitor
      kenpaullone antagonized the effects of IL-18 protein on TSCC cells in vitro. The
      results indicated that IL-18 played an important role in the inhibition of TSCC
      cell growth and may be further investigated as a novel therapeutic target against
      TSCC.

PMID- 25591550
TI  - Evidence for the contribution of genetic variations in regulator of G protein
      signaling 9 to the genetic susceptibility of heroin dependence.
AB  - Regulator of G protein signaling (RGS) proteins are responsible for the rapid
      turnoff of G protein-coupled receptor signaling pathways. RGS9-2, a brain
      specific splice variant of the RGS9 gene, is highly expressed in the striatum but
      lowly expressed in the periaqueductal gray and spinal cord, which mediate various
      actions of morphine and other opiates. In order to identify the markers that
      contribute to the genetic susceptibility of heroin dependence, the potential
      association between heroin dependence and 10 single nucleotide polymorphisms
      (SNPs), including rs8077696, rs8070231, rs2292593, rs2292592, rs9916525,
      rs1122079, rs4790953, rs1530351, rs4791230 and rs2869577 of the RGS9 gene was
      evaluated using the MassARRAY system. The present study recruited 425 heroin
      dependent patients and 205 healthy controls. The results revealed that two SNPs
      (rs1530351 and rs4791230) located in the promoter region of the RGS9 gene, were
      significantly associated with heroin dependence (P<0.05). The frequency of the C
      allele in rs1530351 (chi2=8.031, P=0.005, OR=2.079, 95% CI=1.241-3.483) and the G
      allele in rs4791230 (chi2=7.360, P=0.007, OR=2.021, 95% CI=1.205-3.389) in the
      heroin-dependent patients was significantly higher than that in the controls.
      Furthermore, linkage disequilibrium was observed in three blocks (D'>0.9) and
      significantly less T-A haplotypes (chi2=4.867, P=0.027, OR=0.442, 95% CI=0.210
      0.929) were identified in the heroin-dependent patients, suggesting that they may
      exhibit protective effects against heroin dependence. These findings indicate a
      role for RGS9 gene polymorphisms in heroin dependence and may be informative for
      future genetic or biological studies on heroin dependence.

PMID- 25591549
TI  - Genetic polymorphisms and gene-dosage effect in ovarian cancer risk and response
      to paclitaxel/cisplatin chemotherapy.
AB  - BACKGROUND: Ovarian malignancies are often diagnosed in advanced stage and at the
      same time resistance to treatment, both intrinsic and developed during treatment,
      is sometimes observed. These facts underscore the need for new markers of ovarian
      cancer risk, as well as markers of treatment effectiveness. METHODS: In this
      study we genotyped 225 ovarian cancer patients, 64 breast and ovarian cancer
      patients and 348 healthy controls. In total, 12 polymorphic variants and 2
      deletions in PGR, ABCB1, ABCG2, GSTT1, GSTM1, GSTP1, ATM, TP53 and ATP7B genes
      were analyzed using ASA-PCR, RFLP-PCR, multiplex-PCR and sequencing. RESULTS: Ten
      genetic polymorphisms were significantly associated with the risk of developing
      ovarian carcinoma in at least one of the groups under study. Impact of PGR gene
      polymorphisms on ovarian cancer risk was specific only for the group of the BRCA1
      mutation carriers (in presence of p.Val660Leu variant- OR 2,82; p = 0,010), which
      confirms the difference in modulation of ovarian cancer risk between sporadic and
      hereditary malignancies, including the breast-ovarian cancer group (as a cancer
      prone group). The analyses showed also the importance of ATP7B gene in ovarian
      carcinogenesis, both studied variants of which significantly modulated the
      ovarian cancer risk in all groups excluding the group with BRCA1 mutation.
      Cumulative risk analysis revealed 3 unfavorable variants that increased
      significantly the risk of developing ovarian cancer (p.Ile1145 = ABCB1+
      p.Asp1853Asn ATM+ p.Ser406Ala ATP7B- OR 7,47; p = 0,002) and significantly
      modified the progression free survival (PFS) of the patients, and also two
      favorable genotypes which protected against ovarian cancer (p.Arg952Lys ATP7B+
      p.Arg72Pro TP53- OR 0,50; p = 0,008). PFS analysis for carriers of favorable
      versus unfavorable genotypes emphasized the impact of the regulation of cell
      cycle (p.Asp1853Asn ATM) and active transport of xenobiotics (p.Ser894Ala/Thr
      ABCB1) on the risk of disease progression (HR 3,81; p = 0,010) after
      paclitaxel/cisplatin chemotherapy. CONCLUSIONS: The unfavorable genetic variants
      could facilitate carcinogenic process and once their carriers developed
      malignancy, their chances of survival were smaller. Our analyses also showed a
      strong gene-dosage effect with the decrease of progression-free survival for the
      carriers of two unfavorable genetic factors.

PMID- 25591551
TI  - Prospective assessment of subjective sleep benefit in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) patients may experience 'sleep benefit'
      (SB): a temporarily improved mobility upon awakening. SB has mainly been studied
      retrospectively using questionnaires, but it remains unclear whether it is
      associated with actual changes in motor functioning. METHODS: We performed a
      prospective study on sleep-related changes in motor functioning, using a PD
      symptom diary during 7 days in 240 randomly selected PD patients (140 men; 66.8
      +/- 9.6 years; disease duration 9.3 +/- 6.2 years). Afterwards, patients received
      a questionnaire on the possible subjective experience of SB. RESULTS: Using the
      PD symptom diary, a positive change in motor function was observed after 267
      nights (17.8%) and after 138 daytime naps (23.4%). Based on these results, 75
      patients (32%) were classified as having SB. In response to the subsequent
      questionnaire, 73 patients (31%) reported SB. Interestingly, the groups with SB
      according to either the diary or the questionnaire overlapped only partially:
      outcomes were congruent in 63% of subjects (both negative 49%, both positive
      14%). In both the diary and questionnaire, patients with SB showed a longer
      disease duration and longer medication use. According to the questionnaire, there
      was a trend towards a shorter sleep duration and lower sleep efficiency in the SB
      group. The mean change in motor function after sleep as assessed using the diary
      was higher in patients reporting subjective SB. CONCLUSION: We show that the
      subjective experience of SB in PD is not always related to an actual increase in
      reported motor function after sleep. Defining SB using either a symptom diary or
      a questionnaire on subjective experience, results in only partly overlapping
      groups. These data suggest that SB may be a more heterogeneous phenomenon than
      previously thought and that subjective experience of symptom severity is not
      necessarily related to actual motor function.

PMID- 25591553
TI  - Advances in China's organ transplantation achieved with the guidance of law.

PMID- 25591552
TI  - Bioelectric patterning during oogenesis: stage-specific distribution of membrane
      potentials, intracellular pH and ion-transport mechanisms in Drosophila ovarian
      follicles.
AB  - BACKGROUND: Bioelectric phenomena have been found to exert influence on various
      developmental and regenerative processes. Little is known about their possible
      functions and the cellular mechanisms by which they might act during Drosophila
      oogenesis. In developing follicles, characteristic extracellular current patterns
      and membrane-potential changes in oocyte and nurse cells have been observed that
      partly depend on the exchange of protons, potassium ions and sodium ions. These
      bioelectric properties have been supposed to be related to various processes
      during oogenesis, e. g. pH-regulation, osmoregulation, cell communication, cell
      migration, cell proliferation, cell death, vitellogenesis and follicle growth.
      Analysing in detail the spatial distribution and activity of the relevant ion
      transport mechanisms is expected to elucidate the roles that bioelectric
      phenomena play during oogenesis. RESULTS: To obtain an overview of bioelectric
      patterning along the longitudinal and transversal axes of the developing
      follicle, the spatial distributions of membrane potentials (Vmem), intracellular
      pH (pHi) and various membrane-channel proteins were studied systematically using
      fluorescent indicators, fluorescent inhibitors and antisera. During mid
      vitellogenic stages 9 to 10B, characteristic, stage-specific Vmem-patterns in the
      follicle-cell epithelium as well as anteroposterior pHi-gradients in follicle
      cells and nurse cells were observed. Corresponding distribution patterns of
      proton pumps (V-ATPases), voltage-dependent L-type Ca(2+)-channels, amiloride
      sensitive Na(+)-channels and Na(+),H(+)-exchangers (NHE) and gap-junction
      proteins (innexin 3) were detected. In particular, six morphologically
      distinguishable follicle-cell types are characterized on the bioelectric level by
      differences concerning Vmem and pHi as well as specific compositions of ion
      channels and carriers. Striking similarities between Vmem-patterns and activity
      patterns of voltage-dependent Ca(2+)-channels were found, suggesting a mechanism
      for transducing bioelectric signals into cellular responses. Moreover, gradients
      of electrical potential and pH were observed within single cells. CONCLUSIONS:
      Our data suggest that spatial patterning of Vmem, pHi and specific membrane
      channel proteins results in bioelectric signals that are supposed to play
      important roles during oogenesis, e. g. by influencing spatial coordinates,
      regulating migration processes or modifying the cytoskeletal organization.
      Characteristic stage-specific changes of bioelectric activity in specialized cell
      types are correlated with various developmental processes.

PMID- 25591554
TI  - Adenosine sensitivity is associated with ablation success rate and recurrence
      rate with nonirrigated catheters in patients with ventricular premature
      contractions/tachycardia from the ventricular outflow tract.
AB  - BACKGROUND: A high ablation success rate for ventricular arrhythmia (VA) from
      outflow tract has been achieved, but some of them cannot be eliminated from
      endocardium. We investigated the association between adenosine sensitivity and
      ablation success/recurrence rates with a nonirrigated or an irrigated catheter.
      METHODS: According to adenosine test, all patients were divided into a sensitive
      group (S group) or an insensitive group (I group). The patients of each group
      were randomized into a nonirrigated catheter (NA) subgroup or an irrigated
      catheter (IA) subgroup with a 2:1 ratio. RESULTS: In S group of 122 patients (84
      in NA subgroup), the ablation success rate was similar between two subgroups
      (94.7% vs. 90.5%, P > 0.05), but in I group of 94 patients (60 in NA subgroup),
      it was higher in IA subgroup (94.1%) than that in NA subgroup (73.3%, P < 0.05).
      The success rate using nonirrigated catheter was significantly higher in S group
      (90.5%) than that in I group (73.3%, P < 0.01), and the recurrence rate was lower
      in S group than that in I group (1.3%, vs. 13.6%, P < 0.05). On the contrary, the
      success rate and the recurrence rate using irrigated catheter were similar
      between S group and I group (94.7%, 94.1%, P > 0.05, vs. 2.8%, 6.3%, P > 0.05).
      CONCLUSIONS: Adenosine insensitivity is associated with a lower success rate and
      a higher recurrence rate for VA patients undergoing nonirrigated catheter
      ablation. Thus, irrigated catheters should be the first choice for VA ablation in
      adenosine insensitive patients.

PMID- 25591555
TI  - Valsartan decreases platelet activity and arterial thrombotic events in elderly
      patients with hypertension.
AB  - BACKGROUND: Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used
      for blood pressure control in elderly patients with hypertension. This study
      aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on
      platelet aggregation and the occurrence of cardio-cerebral thrombotic events in
      elderly patients with hypertension. METHODS: Two-hundred and ten patients with
      hypertension and aged > 60 years were randomized to valsartan (n = 140) or
      amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation
      rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint
      was the rate of thrombotic events including brain infarction and myocardial
      infarction during follow-up. Human aortic endothelial cells (HAECs) were
      stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of
      valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and
      thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK)
      and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were
      performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California,
      USA). RESULTS: PAR was lower after treatment with valsartan (11.49 +/- 0.69% vs.
      18.71 +/- 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2
      (76.94 +/- 7.07 U/L vs. 116.4 +/- 15.89 U/L, P < 0.001) and TXB 2 (1667 +/- 56.50
      pg/ml vs. 2207 +/- 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels
      correlated significantly with PAR in overall patients (r = 0.109, P < 0.001).
      During follow-up (median, 18 months), there was a significantly lower thrombotic
      event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002).
      Relative expression of COX-2 and secretion of TXB 2 with concordant
      phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by
      Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment
      (100 nmol/L). CONCLUSIONS: AT 1 R antagonist valsartan decreases platelet
      activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways
      and reduces the occurrence of cardio-cerebral thrombotic events in elderly
      patients with hypertension.

PMID- 25591556
TI  - Analysis of serum metabolic profile by ultra-performance liquid chromatography
      mass spectrometry for biomarkers discovery: application in a pilot study to
      discriminate patients with tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) is a chronic wasting inflammatory disease
      characterized by multisystem involvement, which can cause metabolic derangements
      in afflicted patients. Metabolic signatures have been exploited in the study of
      several diseases. However, the serum that is successfully used in TB diagnosis on
      the basis of metabolic profiling is not by much. METHODS: Orthogonal partial
      least-squares discriminant analysis was capable of distinguishing TB patients
      from both healthy subjects and patients with conditions other than TB. Therefore,
      TB-specific metabolic profiling was established. Clusters of potential biomarkers
      for differentiating TB active from non-TB diseases were identified using Mann
      Whitney U-test. Multiple logistic regression analysis of metabolites was
      calculated to determine the suitable biomarker group that allows the efficient
      differentiation of patients with TB active from the control subjects. RESULTS:
      From among 271 participants, 12 metabolites were found to contribute to the
      distinction between the TB active group and the control groups. These metabolites
      were mainly involved in the metabolic pathways of the following three
      biomolecules: Fatty acids, amino acids, and lipids. The receiver operating
      characteristic curves of 3D, 7D, and 11D-phytanic acid, behenic acid, and
      threoninyl-gamma-glutamate exhibited excellent efficiency with area under the
      curve (AUC) values of 0.904 (95% confidence interval [CI]: 0863-0.944), 0.93 (95%
      CI: 0.893-0.966), and 0.964 (95% CI: 00.941-0.988), respectively. The largest and
      smallest resulting AUCs were 0.964 and 0.720, indicating that these biomarkers
      may be involved in the disease mechanisms. The combination of
      lysophosphatidylcholine (18:0), behenic acid, threoninyl-gamma-glutamate, and
      presqualene diphosphate was used to represent the most suitable biomarker group
      for the differentiation of patients with TB active from the control subjects,
      with an AUC value of 0.991. CONCLUSION: The metabolic analysis results identified
      new serum biomarkers that can distinguish TB from non-TB diseases. The
      metabolomics-based analysis provides specific insights into the biology of TB and
      may offer new avenues for TB diagnosis.

PMID- 25591557
TI  - Identification of differentially expressed microRNAs in the ovary of polycystic
      ovary syndrome with hyperandrogenism and insulin resistance.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in
      women of reproductive age. The patients often develop insulin resistance (IR) or
      hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism.
      The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA)
      is still debated. Micro-ribonucleic acids (miRNAs) have recently been shown to
      play a role in regulation of ovarian function. Our current study focused on the
      altered expression of miRNAs with PCOS. METHODS: Ovarian theca interna tissues
      were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had
      normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection.
      Total RNA of all samples was extracted. We studied the repertoire of miRNAs in
      both PCOS and non-PCOS women by microarray hybridization. Bioinformatic analysis
      was performed for predicting targets of the differentially expressed miRNAs.
      Furthermore, selected miRNAs were validated by quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR). RESULTS: A total of 27 miRNAs were
      differentially expressed in PCOS patients with respect to the controls in our
      discovery evaluationand two (miR-92a and miR-92b) of them were significantly
      downregulated in PCOS women in followed validation (P < 0.05). Targets prediction
      revealed that miR-92a targeted both GATA family of zinc finger transcription
      factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2
      (IRS-2). CONCLUSIONS: MiRNAs are differentially expressed between PCOS patients
      and controls. We identified and validated two miRNAs-miR-92a and miR-92b. They
      are significantly downregulated and may be involved in the pathogenesis of PCOS.

PMID- 25591558
TI  - Differentiation of renal oncocytoma and renal clear cell carcinoma using relative
      CT enhancement ratio.
AB  - BACKGROUND: The difference between renal oncocytomas (RO) and renal clear cell
      carcinomas (RCCs) presents the greatest diagnostic challenge. The aim of this
      study was to retrospectively determine if RO and RCCs could be differentiated on
      computed tomography (CT) images on the basis of their enhancement patterns with a
      new enhancement correcting method. METHODS: Forty-six patients with a solitary
      renal mass who underwent total or partial nephrectomy were included in this
      study. Fourteen of those were RO and 32 were RCCs. All patients were examined
      with contrast-enhanced CT. The pattern and degree of enhancement were evaluated.
      We selected the area that demonstrated the greatest degree of enhancement of the
      renal lesion in the corticomedullary nephrographic and excretory phase images.
      Regions of interest (ROI) were also placed in adjacent normal renal cortex for
      normalization. We used the values of the normal renal cortex that were measured
      at the same time as divisors. The ratios of lesion-to-renal cortex enhancement
      were calculated for all three phases. The Student's t-test and Pearson's Chi
      square test were used for statistical analyses. RESULTS: All RCCs masses showed
      contrast that appeared to be better enhanced than RO on all contrast-enhanced
      phases of CT imaging, but there was no significant difference in absolute
      attenuation values between these two diseases (P > 0.05). The ratio of lesion-to
      cortex attenuation in the corticomedullary phase showed significantly different
      values between RO and RCCs. The degree of contrast enhancement in RCCs was equal
      to or greater than that of the normal renal cortex, but it was less than that of
      the normal cortex in RO in the corticomedullary phase. The ratio of lesion-to
      cortex attenuation in the corticomedullary phase was higher than the cut off
      value of 1.0 in most RCCs (84%, 27/32) and lower than 1.0 in most RO (93%, 13/14)
      (P < 0.05). In the nephrographic phase, the ratio of lesion-to-cortex attenuation
      was higher than that in the corticomedullary phase in most RO (71%, 10/14),
      showing a prolonged enhancement pattern; and was lower than that in most RCCs
      (97%, 31/32), showing an early washout pattern (P < 0.05). In the differentiation
      of RO from RCCs, the sensitivity was 93%, specificity 84%, positive predictive
      value 72%, negative predictive value 84%, and accuracy for RO was 87, if the
      ratio of lesion-to-cortex attenuation in a cortex phase was lower than the cutoff
      value of 1.0. The sensitivity was 71%, specificity was 97%, positive predictive
      value was 91%, negative predictive value was 91%, and accuracy for RO was 89%, if
      the ratio of lesion-to-cortex attenuation in nephrographic phase was higher than
      that in the corticomedullary phase. CONCLUSIONS: The ratios of renal lesion-to
      cortex attenuation ratios may be helpful in differentiating RO from RCCs.

PMID- 25591559
TI  - Effect of aldehyde dehydrogenase 2 gene polymorphism on hemodynamics after
      nitroglycerin intervention in Northern Chinese Han population.
AB  - BACKGROUND: Nitroglycerin (NTG) is one of the few immediate treatments for acute
      angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that
      facilitates the biological metabolism of NTG. The biological mechanism of NTG
      serves an important function in NTG efficacy. Some reports still contradict the
      results that the correlation between ALDH2 gene polymorphisms and NTG and its
      clinical efficacy is different. However, data on NTG measurement by pain relief
      are subjective. This study aimed to investigate the influence of ALDH2 gene
      polymorphism on intervention with sublingual NTG using noninvasive hemodynamic
      parameters of cardiac output (CO) and systemic vascular resistance (SVR) in
      Northern Chinese Han population. METHODS: This study selected 559 patients from
      the Affiliated Hospital of Qingdao University. A total of 203 patients presented
      with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient
      ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and
      mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were
      mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant
      type among the NCHD volunteers. A noninvasive hemodynamic detector was used to
      monitor the CO and the SVR at the 0, 5, and 15 minute time points after
      medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a
      comparative analysis of all case genotypes. RESULTS: Both CO and SVR indicators
      significantly differed between the wild and mutant genotypes at various time
      points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F
      = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P =
      0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups
      increased, whereas those in the mutant type decreased. The CO and DeltaCO
      differences were statistically significant (P < 0.05; P < 0.05). The SVR and
      DeltaSVR changed between the wild- and mutant-type cases at all-time points in
      both NCHD and CHD groups had statistically significant differences (P < 0.05; P <
      0.05). CONCLUSION: ALDH2 (G504A) gene polymorphism is associated with changes in
      noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with
      sublingual NTG. This gene polymorphism may influence the effect of NTG
      intervention on Northern Chinese Han population.

PMID- 25591560
TI  - Diagnostic significance of intraoperative ultrasound contrast in evaluating the
      resection degree of brain glioma by transmission electron microscopic
      examination.
AB  - BACKGROUND: Contrast-enhanced ultrasound is a dynamic and continuous modality
      providing real-time view of vascularization and flow distribution patterns of
      different organs and tumors. In order to evaluate the diagnostic significance of
      intraoperative contrast-enhanced ultrasound in assessing the resection degree of
      brain glioma by transmission electron microscopic (TEM) examination, it is
      important to have specific knowledge about contrast-enhanced ultrasound. Methods
      : Ultrasound contrast was applied in operations of 120 cases of brain glioma, to
      evaluate the degree of tumor resection. Biopsy tissues were obtained the
      suspicious residual tumors surrounding the tumor cavity. The sensitivity and
      specificity of the residual tumors were determined by the intraoperative
      ultrasound contrast according to TEM examination results. RESULTS: There were 44
      cases of low-grade gliomas and 76 cases of high-grade gliomas. Three hundred and
      sixty biopsy tissues were obtained. The sensitivity of intraoperative ultrasound
      contrast in diagnosing the residual tumor was 62.2%, while the specificity degree
      of it was 92.8%. The consistency coefficient of the ultrasound contrast diagnosis
      and TEM examination results was 0.584 (Kappa = 0.584), which was between 0.4 and
      0.6, therefore it was of medium consistency. Conclusions : Intraoperative
      ultrasound contrast was of a high sensitivity and specificity in evaluating the
      excision degree of tumor. The consistency of the residual tumor rate detected,
      respectively, by ultrasound contrast and TEM examination was of medium
      consistency. The application of intraoperative ultrasound contrast can improve
      the resection rate of brain glioma.

PMID- 25591561
TI  - Evaluations of computed tomography images and lumbar specimens in mimic
      operations of transverse rotation laminoplasty for lumbar spinal stenosis.
AB  - BACKGROUND: Laminectomy is a major method to treat lumbar spinal stenosis (LSS),
      but it has lots of flaws such as scar tissue can form around the dura again or
      spinal instability. This study aimed to investigate the feasibility of transverse
      rotation laminoplasty (TRL) in the treatment of LSS. METHODS: The mimic
      operations of TRL were performed both in the computerized image processing and on
      the lumbar specimen. Computed tomography (CT) images were either collected from
      80 clinical patients with complaints of lumbago or obtained from 40 sets of
      lumbar specimens after rebuild of spinal canals. In the CT image processing the
      heights of the spinous process and laminae at L3-L5 were measured. The total
      length of the spinous process plus one side laminae after the operation was
      evaluated and compared with the length of inner margin of pedical before the
      operation. The areas of the vertebral canal were examined before and after the
      operation. RESULTS: In the CT images, the height of spinous process of L3, L4 and
      L5 was 24.74 +/- 3.45, 22.68 +/- 5.96 and 21.54 +/- 4.12 mm respectively, and
      that of laminae was 23.66 +/- 2.32, 22.68 +/- 5.36 and 20.99 +/- 3.67 mm
      respectively (P > 0.05). Distance of inner border of pedical of L3, L4 and L5 was
      23.01 +/- 6.59, 24.65 +/- 5.54 and 26.03 +/- 7.34 mm respectively, and length of
      spinous process with laminae of those was 29.76 +/- 4.91, 29.31 +/- 6.43 and
      32.53 +/- 5.76 mm respectively (P < 0.05). Preoperative area of spinal canals of
      L3, L4 and L5 was 299.81 +/- 10.09, 297.66 +/- 9.54 and 308.22 +/- 10.04 mm2
      respectively, and postoperative area was 480.01 +/- 9.33, 487.32 +/- 8.65 and
      501.03 +/- 9.12 mm2 respectively (P < 0.05). In the human lumbar vertebrae
      specimen, the data similar to the former. CONCLUSIONS: The excised canal
      posterior was covered, and the lumbar canals enlarged by TRL. The TRL provided a
      new alternative in the treatment of LSS.

PMID- 25591562
TI  - Footprint mismatch of cervical disc prostheses with Chinese cervical anatomic
      dimensions.
AB  - BACKGROUND: The footprint of most prostheses is designed according to Caucasian
      data. Total disc replacement (TDR) has been performed widely for cervical
      degenerative diseases in China. It is essential to analyze the match sizes of
      prostheses footprints and Chinese cervical anatomic dimensions in our study.
      METHODS: The anatomic dimensions of the C4-C7 segments of 138 patients (age range
      16-77 years) in a Chinese population were measured by computed tomography scans.
      We compared the footprints of the most commonly used cervical disc prostheses
      (Bryan: Medtronic, Minneapolis, MN, USA; Prestige LP: Medtronic, Fridley,
      Minnesota, USA; Discover: DePuy, Raynham, MA, USA; Prodisc-C: Synthes, West
      Chester, PA, USA) in China with Chinese cervical anatomic dimensions and assessed
      the match of their size. RESULTS: The mismatch of available dimensions of
      prostheses and anatomic data of cervical endplates ranged from 17.03% (C4/C5,
      Prestige LP, Prodisc-C) to 57.61% (C6/C7, Discover) in the anterior-posterior
      (AP) diameter, and 35.51% (C4/C5, Prodisc-C, Prestige LP) to 94.93% (C6/C7,
      Bryan) in the center mediolateral (CML) diameter. About 21.01% of endplates were
      larger than the largest prostheses in the AP diameter and 57.25% in the CML
      diameter. All available footprints of prostheses expect the Bryan with an unfixed
      height, can accommodate the disc height (DH), however, 36.23% of the middle DH
      was less than the smallest height of the prostheses. The average disc sagittal
      angles (DSAs) of C4-C7 junctions were 5.04 degrees , 5.15 degrees , and 4.13
      degrees  respectively. Only the Discover brand had a built-in 7 degrees  lordotic
      angle, roughly matching with the DSA. CONCLUSIONS: There is a large discrepancy
      between footprints of prostheses and Chinese cervical anatomic data. In recent
      years, possible complications of TDR related with mismatch sizes are increasing,
      such as subsidence, displacement, and heterotopic ossification. Manufacturers of
      prostheses should introduce or produce additional footprints of prostheses for
      Chinese TDR.

PMID- 25591564
TI  - Treatment of epilepsy with bipolar electro-coagulation: an analysis of cortical
      blood flow and histological change in temporal lobe.
AB  - BACKGROUND: Bipolar electro-coagulation has a reported efficacy in treating
      epilepsy involving functional cortex by pure electro-coagulation or combination
      with resection. However, the mechanisms of bipolar electro-coagulation are not
      completely known. We studied the acute cortical blood flow and histological
      changes after bipolar electro-coagulation in 24 patients with intractable
      temporal lobe epilepsy. METHODS: Twenty-four patients were consecutively
      enrolled, and divided into three groups according to the date of admission. The
      regional cortical blood flow (rCBF), electrocorticography, the depth of cortex
      damage, and acute histological changes (H and E staining, neuronal staining and
      neurofilament (NF) staining) were analyzed before and after the operation. The t
      test analysis was used to compare the rCBF before and after the operation.
      RESULTS: The rCBF after coagulation was significantly reduced (P < 0.05). The
      spikes were significantly reduced after electro-coagulation. For the temporal
      cortex, the depth of cortical damage with output power of 2-9 W after electro
      coagulation was 0.34 +/- 0.03, 0.48 +/- 0.06, 0.69 +/- 0.06, 0.84 +/- 0.09, 0.98
      +/- 0.08, 1.10 +/- 0.11, 1.11 +/- 0.09, and 1.22 +/- 0.11 mm, respectively.
      Coagulation with output power of 4-5 W completely damaged the neurons and NF
      protein in the molecular layer, external granular layer, and external pyramidal
      layer. CONCLUSIONS: The electro-coagulation not only destroyed the neurons and NF
      protein, but also reduced the rCBF. We concluded that the injuries caused by
      electro-coagulation would prevent horizontal synchronization and spread of
      epileptic discharges, and partially destroy the epileptic focus.

PMID- 25591563
TI  - Solid lipid nanoparticles loaded with edaravone for inner ear protection after
      noise exposure.
AB  - BACKGROUND: Antioxidants and the duration of treatment after noise exposure on
      hearing recovery are important. We investigated the protective effects of an
      antioxidant substance, edaravone, and its slow-release dosage form, edaravone
      solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. METHODS:
      SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone
      solution or edaravone SLNs were administered by intratympanic or intravenous
      injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110
      dB sound pressure level (SPL) noise, centered at 0.25-4.0 kHz, for 4 days at 2
      h/d. After noise exposure, the guinea pigs underwent auditory brainstem response
      (ABR) threshold measurements, reactive oxygen species (ROS) were detected in
      their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs)
      were counted with silvernitrate (AgNO 3 ) staining at 1, 4, and 6 days. RESULTS:
      The ultrasound technique was able to prepare adequate edaravone SLNs with a mean
      particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress
      induced ROS formation and edaravone exerted a protective effect on the cochlea.
      Comparisons of hearing thresholds and ROS changes in different animal groups
      showed that the threshold shift and ROS generation were significantly lower in
      treated animals than in those without treatment, especially in the edaravone SLN
      intratympanic injection group. CONCLUSIONS: Edaravone SLNs show noticeable slow
      release effects and have certain protective effects against noise-induced hearing
      loss (NIHL).

PMID- 25591565
TI  - Kinematic analysis of a posterior-stabilized knee prosthesis.
AB  - BACKGROUND: The goal of total knee arthroplasty (TKA) is to restore knee
      kinematics. Knee prosthesis design plays a very important role in successful
      restoration. Here, kinematics models of normal and prosthetic knees were created
      and validated using previously published data. METHODS: Computed tomography and
      magnetic resonance imaging scans of a healthy, anticorrosive female cadaver were
      used to establish a model of the entire lower limbs, including the femur, tibia,
      patella, fibula, distal femur cartilage, and medial and lateral menisci, as well
      as the anterior cruciate, posterior cruciate, medial collateral, and lateral
      collateral ligaments. The data from the three-dimensional models of the normal
      knee joint and a posterior-stabilized (PS) knee prosthesis were imported into
      finite element analysis software to create the final kinematic model of the TKA
      prosthesis, which was then validated by comparison with a previous study. The
      displacement of the medial/lateral femur and the internal rotation angle of the
      tibia were analyzed during 0-135 degrees  flexion. RESULTS: Both the output data
      trends and the measured values derived from the normal knee's kinematics model
      were very close to the results reported in a previous in vivo study, suggesting
      that this model can be used for further analyses. The PS knee prosthesis
      underwent an abnormal forward displacement compared with the normal knee and has
      insufficient, or insufficiently aggressive, "rollback" compared with the lateral
      femur of the normal knee. In addition, a certain degree of reverse rotation
      occurs during flexion of the PS knee prosthesis. CONCLUSIONS: There were still
      several differences between the kinematics of the PS knee prosthesis and a normal
      knee, suggesting room for improving the design of the PS knee prosthesis. The
      abnormal kinematics during early flexion shows that the design of the articular
      surface played a vital role in improving the kinematics of the PS knee
      prosthesis.

PMID- 25591566
TI  - New classification of Herlyn-Werner-Wunderlich syndrome.
AB  - BACKGROUND: Uterus didelphys and blind hemivagina associated with ipsilateral
      renal agenesis are collectively known as Herlyn-Werner-Wunderlich syndrome
      (HWWS). In the literature, the syndrome often appears as a single case report or
      as a small series. In our study, we reviewed the characteristics of all HWWS
      patients at Peking Union Medical College Hospital (PUMCH) and suggested a new
      classification for this syndrome because the clinical characteristics differed
      significantly between the completely and incompletely obstructed vaginal septum.
      This new classification allows for earlier diagnosis and treatment. METHODS: From
      January 1986 to March 2013, all diagnosed cases of HWWS at PUMCH were reviewed. A
      retrospective long-term follow-up study of the clinical presentation, surgical
      prognosis, and pregnancy outcomes was performed. Statistical analyses were
      performed using SPSS, version 15.0 (IBM, Armonk, NY, USA). Between-group
      comparisons were performed using the chi2 test, Fisher's exact test, and the t
      test. The significance level for all analyses was set at P < 0.05. RESULTS: The
      clinical data from 79 patients with HWWS were analyzed until March 31, 2013.
      According to our newly identified characteristics, we recommend that the syndrome
      be classified by the complete or incomplete obstruction of the hemivagina as
      follows: Classification 1, a completely obstructed hemivagina and Classification
      2, an incompletely obstructed hemivagina. The clinical details associated with
      these two types are distinctly different. CONCLUSIONS: HWWS patients should be
      differentiated according to these two classifications. The two classifications
      could be generalized by gynecologists world-wide.

PMID- 25591567
TI  - Early detection of regional and global left ventricular myocardial function using
      strain and strain-rate imaging in patients with metabolic syndrome.
AB  - BACKGROUND: Strain and strain-rate imaging (SRI) have been found clinically
      useful in the assessment of cardiac systolic and diastolic function as well as
      providing new insights in deciphering cardiac physiology and mechanics in
      cardiomyopathies, and identifying early subclinical changes in various
      pathologies. The aim of this study was to evaluate the regional and global left
      ventricular (LV) myocardial function in metabolic syndrome (MS) with SRI so that
      we can provide more myocardial small lesions in patients with MS, which is robust
      and reliable basis for early detection of LV function. METHODS: Thirty-nine
      adults with MS were enrolled in the study. There was a control group of 39
      healthy adults. In addition to classic echocardiographic assessment of LV global
      functional changes, SRI was used to evaluate regional and global LV function.
      Including: Peak systolic strain (S), peak systolic strain-rate (SR-s), peak
      diastolic strain-rate (SR-e). RESULTS: There were no statistically significant
      differences between MS and controls in all traditional parameters of LV systolic
      function. On the other hand, significant differences were observed between MS and
      the control group in most of the parameters of S, SR-s, SR-e in regional LV
      function. Multiple stepwise regression analyses revealed that S and SR
      significantly were negatively correlated with blood pressure, waist
      circumference, fasting plasma glucose, uric acid, suggesting that risk factories
      were relevant to regional systolic dysfunction. CONCLUSION: In MS with normal LV
      ejection fraction, there was regional myocardial dysfunction, risk factors
      contributed to the impairment of systolic and diastolic function of the regional
      myocardium. Assessment of myocardial function using SRI could be more accurate in
      MS patient evaluation than conventional echocardiography alone.

PMID- 25591568
TI  - Discriminating potential of extraintestinal systemic manifestations and
      colonoscopic features in Chinese patients with intestinal Behcet's disease and
      Crohn's disease.
AB  - BACKGROUND: The distinction between intestinal Behetaet's disease (BD) and
      Crohn's disease (CD) is always challenging due to many overlapping clinical
      features. We conducted a retrospective study to reveal valuable strategies for
      the differential diagnosis between intestinal BD and CD in Chinese patients based
      on their clinical and colonoscopic features. METHODS: Thirty-five intestinal BD
      patients and 106 CD patients hospitalized from January 1983 to January 2010, who
      had ulcerative lesions in the terminal ileum or colon under colonoscopy and no
      history of gastrointestinal operation except appendectomy before admission, were
      enrolled. Univariate and multivariate logistic regression analyses were conducted
      to find discriminating predictors among demographic data, clinical
      manifestations, and colonoscopic findings. RESULTS: Based on univariate analysis,
      massive gastrointestinal hemorrhage, fever, and extraintestinal systemic
      manifestations were more common in intestinal BD patients (P = 0.022, 0.048 and
      0.001, respectively), while diarrhea, intestinal obstruction, and perianal
      lesions were more common in CD patients (P = 0.002, 0.010, and 0.027
      respectively). Based on colonoscopy, focal involvement, ileocecal valve
      deformity, solitary ulcers, large ulcers (ulcer size > 2 cm), and circumferential
      ulcers were more common in intestinal BD patients (P = 0.003, 0.003, 0.014,
      0,013, and 0.003, respectively), while segmental involvement, longitudinal
      ulcers, a cobblestone or nodular appearance, and pseudo-polyps were more common
      in CD patients (P = 0.003, 0.008, 0.023, and 0.002, respectively). Based on
      multivariate logistic regression analysis, diarrhea, extraintestinal
      manifestations, ulcer distribution, size, and type, and pseudo-polyps were
      independent discriminating predictors between the two groups (P = 0.048, 0.008,
      0.006, 0.021, 0.002, and 0.041, respectively). The discriminating algorithm
      composed of the above independent predictors had the highest area under the curve
      of 0.987 for distinguishing between the two diseases. CONCLUSIONS:
      Extraintestinal systemic manifestations and the characteristic colonoscopic
      features, such as ulcer distribution, size and type, helped to distinguish
      intestinal BD from CD.

PMID- 25591569
TI  - Increased orexin expression promotes sleep/wake disturbances in the SOD1-G93A
      mouse model of amyotrophic lateral sclerosis.
AB  - BACKGROUND: Sleep/wake disturbances in patients with amyotrophic lateral
      sclerosis (ALS) are well-documented, however, no animal or mechanistic studies on
      these disturbances exist. Orexin is a crucial neurotransmitter in promoting
      wakefulness in sleep/wake regulation, and may play an important role in sleep
      disturbances in ALS. In this study, we used SOD1-G93A transgenic mice as an ALS
      mouse model to investigate the sleep/wake disturbances and their possible
      mechanisms in ALS. METHODS: Electroencephalogram/electromyogram recordings were
      performed in SOD1-G93A transgenic mice and their littermate control mice at the
      ages of 90 and 120 days, and the samples obtained from these groups were
      subjected to quantitative reverse transcriptase-polymerase chain reaction,
      western blotting, and enzyme-linked immunosorbent assay. RESULTS: For the first
      time in SOD1-G93A transgenic mice, we observed significantly increased
      wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin
      A and B) at both 90 and 120 days. Correlation analysis confirmed moderate to high
      correlations between sleep/wake time (total sleep time, wakefulness time, rapid
      eye movement [REM] sleep time, non-REM sleep time, and deep sleep time) and
      increase in orexins (prepro-orexin, orexin A and B). CONCLUSION: Sleep/wake
      disturbances occur before disease onset in this ALS mouse model. Increased
      orexins may promote wakefulness and result in these disturbances before and after
      disease onset, thus making them potential therapeutic targets for amelioration of
      sleep disturbances in ALS. Further studies are required to elucidate the
      underlying mechanisms in the future.

PMID- 25591570
TI  - Effect of glutamine enriched nutrition support on surgical patients with
      gastrointestinal tumor: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Associations between glutamine (Gln) enriched nutrition support and
      surgical patients with gastrointestinal (GI) tumor remain controversy. The
      purpose of this meta-analysis was to assess the effect of Gln enriched nutrition
      support on surgical patients with GI tumor in term of relevant biochemical
      indices, immune indices, and clinical outcomes. METHODS: Six databases were
      systematically searched to find eligible randomized controlled trials (RCTs) from
      1966 to May 2014. When estimated the analysis indexes, the relative risk (RR) was
      used as the effect size of the categorical variable, while the weighted mean
      difference (MD) was used as the effect size of a continuous variable. Meta
      analysis was conducted with Rev Man 5.2. RESULTS: Thirteen RCTs, involving 1034
      patients, were included in the meta-analysis. The analysis showed that Gln
      enriched nutrition support was more effective in increasing serum albumin (MD:
      0.10; 95% confidence interval [CI]: 0.02-0.18; P < 0.05), serum prealbumin (MD:
      1.98; 95% CI: 1.40-2.55; P < 0.05) and serum transferring (MD: 0.35; 95% CI: 0.12
      0.57; P < 0.05), concentration of IgG (MD: 1.26; 95% CI: 0.90-1.63; P < 0.05),
      IgM (MD: 0.18; 95% CI: 0.11-0.25; P < 0.05), IgA (MD: 0.22; 95% CI: 0.10-0.33; P
      < 0.05), CD3 + (MD: 3.71; 95% CI: 2.57-4.85; P < 0.05) and CD4/CD8 ratio (MD:
      0.27; 95% CI: 0.12-0.42; P < 0.05). Meanwhile, it was more significant in
      decreasing the incidence of infectious complications (RR: 0.67; 95% CI: 0.50
      0.90; P < 0.05) and shortening the length of hospital stay (MD: -1.72; 95% CI: 
      3.31--0.13; P < 0.05). CONCLUSIONS: Glutamine enriched nutrition support was
      superior in improving immune function, reducing the incidence of infectious
      complications and shortening the length of hospital stay, playing an important
      role in the rehabilitation of surgical GI cancer patients.

PMID- 25591571
TI  - Current strategies for quantitating fibrosis in liver biopsy.
AB  - OBJECTIVE: The present mini-review updated the progress in methodologies based on
      using liver biopsy. DATA SOURCES: Articles for study of liver fibrosis, liver
      biopsy or fibrosis assessment published on high impact peer review journals from
      1980 to 2014. STUDY SELECTION: Key articles were selected mainly according to
      their levels of relevance to this topic and citations. RESULTS: With the recently
      mounting progress in chronic liver disease therapeutics, comes by a pressing need
      for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis
      in individual patients. Histopathological information is recognized as the most
      valuable data for fibrosis assessment. Conventional histology categorical systems
      describe the changes of fibrosis patterns in liver tissue; but the simplified
      ordinal digits assigned by these systems cannot reflect the fibrosis dynamics
      with sufficient precision and reproducibility. Morphometric assessment by
      computer assist digital image analysis, such as collagen proportionate area
      (CPA), detects change of fibrosis amount in tissue section in a continuous
      variable, and has shown its independent diagnostic value for assessment of
      advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling
      variances, morphometric measurement is feasible to be taken as a reliable
      statistical parameter for the study of a large cohort. Combining state-of-art
      imaging technology and fundamental principle in Tissue Engineering, structure
      based quantitation was recently initiated with a novel proof-of-concept tool,
      qFibrosis. qFibrosis showed not only the superior performance to CPA in
      accurately and reproducibly differentiating adjacent stages of fibrosis, but also
      the possibility for facilitating analysis of fibrotic regression and cirrhosis
      sub-staging. CONCLUSIONS: With input from multidisciplinary innovation, liver
      biopsy assessment as a new "gold standard" is anticipated to substantially
      support the accelerated progress of Hepatology medicine.

PMID- 25591572
TI  - Use of atorvastatin in lipid disorders and cardiovascular disease in Chinese
      patients.
AB  - OBJECTIVE: Statins are still underused for the prevention of cardiovascular
      disease (CVD) in China. Hence, we conducted a systemic review on the
      pharmacology, clinical efficacy, and adverse events of atorvastatin, as well as
      on patient adherence. DATA SOURCES: We conducted a systemic search in PubMed with
      the following keywords: "atorvastatin" (Supplementary concept) or "atorvastatin"
      (All field) and ("China" [AD] or "China" [all field] or "Chinese" [All field]).
      STUDY SELECTION: Clinical or basic research articles on atorvastatin were
      included. RESULTS: Atorvastatin is a reversible and competitive inhibitor of 3
      hydroxy-3-methylglutaryl-coenzyme A reductase, decreasing the de novo cholesterol
      synthesis. The pharmacokinetics of atorvastatin among Chinese is similar to those
      in Caucasians, and several gene polymorphisms have proved to be associated with
      the metabolism of atorvastatin in the Chinese population. Several international
      multiple-center randomized control trials have demonstrated the benefit of
      atorvastatin for primary and secondary prevention of CVD. None of them, however,
      included the Chinese, and current evidence in the population is still inadequate,
      due to the small sample size, low study quality, short study duration, and the
      use of surrogate endpoints instead of clinical endpoints. The overall incidence
      of adverse events observed with atorvastatin did not increase in the 10-80 mg
      dose range, and was similar to that observed with placebo and in patients treated
      with other statins, which makes atorvastatin well-tolerated in the Chinese
      population. Moreover, high patient adherence was observed in clinical studies.
      CONCLUSIONS: Based on the current available evidence, there is no significant
      difference between Chinese and non-Chinese population in term of pharmacology and
      clinical efficacy/safety. High-quality evidence is still needed to support the
      use of atorvastatin in high-risk Chinese population.

PMID- 25591574
TI  - Eye tumors misdiagnosed as glaucoma.

PMID- 25591573
TI  - Microparticles as novel biomarkers and therapeutic targets in coronary heart
      disease.

PMID- 25591575
TI  - Mediopatellar plica as a risk factor for knee osteoarthritis?

PMID- 25591576
TI  - A review on problems of China's hospice care and analysis of possible solutions.

PMID- 25591577
TI  - Misdiagnosis of liver infarction after cesarean section in a patient with
      antiphospholipid syndrome during pregnancy.

PMID- 25591578
TI  - Purpura associated with lithium intoxication.

PMID- 25591579
TI  - Half-dose gadoxetic acid-enhanced liver magnetic resonance imaging in patients at
      risk for nephrogenic systemic fibrosis.
AB  - PURPOSE: To evaluate the feasibility of half-dose gadoxetic acid (0.0125mmol/kg)
      for liver MRI at 3-T compared to standard-dose (0.025mmol/kg) in patients at risk
      for nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: Forty patients
      who underwent both half-dose and standard-dose gadoxetic acid-enhanced MRIs were
      included. Contrast enhancement index (CEI) was calculated for liver, aorta,
      pancreas and kidney. Two observers independently rated and performed a one-to-one
      direct comparison of enhancement quality for both groups. RESULTS: Liver CEIs
      were not significantly different on arterial phase between the two groups but
      CEIs of standard-dose MRIs were greater than half-dose MRIs on other phases
      (P<0.001). CEIs were not significantly different on arterial phase for the aorta
      or on any phases for the pancreas. Kidney CEIs of standard-dose MRIs were greater
      than half-dose MRIs on all phases (P<0.05). Enhancement quality of both groups
      was diagnostic and did not significantly differ for any organs. In one-to-one
      direct comparisons of enhancement quality, equal ratings were given in 87.5%
      (35/40) of cases by observer 1 and 85.0% (34/40) by observer 2. CONCLUSION: Liver
      MRI using half-dose gadoxetic acid at 3-T can be a feasible alternative for
      standard-dose MRI in patients at risk for NSF.

PMID- 25591580
TI  - Rare idiopathic intestinal pneumonias (IIPs) and histologic patterns in new
      ATS/ERS multidisciplinary classification of the IIPs.
AB  - The new American Thoracic Society/European Respiratory Society (ATS/ERS) update
      to the multidisciplinary classification of idiopathic interstitial pneumonias
      (IIPs) defines both rare IIPs and rare histologic patterns of IIPs. Although
      these diseases are rare, each has some distinguishing imaging and pathologic
      characteristics. Common findings for IIPs in computed tomography (CT) include
      cysts in lymphoid interstitial pneumonia (LIP), upper lobe subpleural
      consolidation in pleuropulmonary fibroelastosis (PPFE), symmetrical consolidation
      in acute fibrinous organizing pneumonia (AFOP), and peribronchovascular
      consolidation or centrilobular nodules in bronchiolocentric pattern of
      interstitial pneumonia. 

PMID- 25591583
TI  - Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia
      patients - worldwide battlefield.
AB  - Advances in understanding the pathogenesis of chronic myeloid leukemia (CML) and
      implementation of the therapy with tyrosine kinase inhibitors (TKI) could be
      considered as a prototype of successful fight against cancer. However, for an
      optimally responding patient it is recommended to follow the TKI therapy
      indefinitely. The question about the possibility of safe TKI treatment
      discontinuation in certain clinical situations was raised and is currently under
      close investigation worldwide. Currently, imatinib discontinuation trails have
      shown that about 60% of eligible patients experienced molecular recurrence within
      6 months of treatment discontinuation, while the remaining 40% remained in
      defined deep molecular response throughout the duration of mostly two years
      follow-up. Interestingly, retreatment with the same TKI or another TKI was
      successful in the vast majority of patients demonstrating molecular recurrence of
      the disease. These findings support the concept of safe TKI treatment
      discontinuation and its usefulness for a specific subset of CML patients.
      However, recent data are not sufficient for TKI discontinuation attempts outside
      clinical trials yet. Because of the high risk of potentially problematic
      molecular recurrences of the pathological clones, the key question is to find the
      right predictive marker of TKI discontinuation success, however it stays unsolved
      yet. This minireview brings a concise summary of this hot topic with a realistic
      view from clinical routine. KEYWORDS: tyrosine kinase inhibitors, imatinib,
      discontinuation, chronic myeloid leukemia.

PMID- 25591581
TI  - Seminal CD38 is a pivotal regulator for fetomaternal tolerance.
AB  - A successful pregnancy depends on a complex process that establishes fetomaternal
      tolerance. Seminal plasma is known to induce maternal immune tolerance to
      paternal alloantigens, but the seminal factors that regulate maternal immunity
      have yet to be characterized. Here, we show that a soluble form of CD38 (sCD38)
      released from seminal vesicles to the seminal plasma plays a crucial role in
      inducing tolerogenic dendritic cells and CD4(+) forkhead box P3(+) (Foxp3(+))
      regulatory T cells (Tregs), thereby enhancing maternal immune tolerance and
      protecting the semiallogeneic fetus from resorption. The abortion rate in BALB/c
      females mated with C57BL/6 Cd38(-/-) males was high compared with that in females
      mated with Cd38(+/+) males, and this was associated with a reduced proportion of
      Tregs within the CD4(+) T-cell pool. Direct intravaginal injection of sCD38 to
      CBA/J pregnant mice at preimplantation increased Tregs and pregnancy rates in
      mice under abortive sonic stress from 48 h after mating until euthanasia. Thus,
      sCD38 released from seminal vesicles to the seminal plasma acts as an
      immunoregulatory factor to protect semiallogeneic fetuses from maternal immune
      responses. 

PMID- 25591582
TI  - P2X7 receptors: role in bone cell formation and function.
AB  - The role of the P2X7 receptor (P2X7R) is being explored with intensive interest
      in the context of normal bone physiology, bone-related diseases and, to an
      extent, bone cancer. In this review, we cover the current understanding of P2X7R
      regulation of bone cell formation, function and survival. We will discuss how the
      P2X7R drives lineage commitment of undifferentiated bone cell progenitors, the
      vital role of P2X7R activation in bone mineralisation and its relatively
      unexplored role in osteocyte function. We also review how P2X7R activation is
      imperative for osteoclast formation and its role in bone resorption via
      orchestrating osteoclast apoptosis. Variations in the gene for the P2X7R (P2RX7)
      have implications for P2X7R-mediated processes and we review the relevance of
      these genetic variations in bone physiology. Finally, we highlight how targeting
      P2X7R may have therapeutic potential in bone disease and cancer.

PMID- 25591584
TI  - MicroRNA 363 mediated positive regulation of c-myc translation affect prostate
      cancer development and progress.
AB  - Prostate cancer (CaP) is the sixth most significant cancer killer of men in
      China. In this study, the potential role of micro-363 (miR-363) in CaP
      development and progression was investigated. Pri-miR-363 or anti-miR-363 was
      transfected into the CaP cells line PC-3 cells. Cell proliferation,
      transformation property, and epithelial-to-mesenchymal transition (EMT) were
      evaluated by MTT, clonogenic assay, colony formation in soft agar and western
      blotting, respectively. The expression and involvement of c-myc, a downstream
      target of miR-363 were also determined. The results showed that endogenous
      expression of miR-363 was significantly increased in CaP cells compared with
      normal prostate cells. High expression of miR-363 in PC-3 cells through
      transfection induces cell proliferation and positively regulates cell
      transformation property as well as promotes EMT of PC-3 cells. Through knockdown
      of c-myc, the results also showed that c-myc was involved in the regulation of
      biological function of PC-3 cells by miR-363. Taken together, this study adds
      support to the potential role of miR-363 in the diagnosis and treatment of CaP.
      KEYWORDS: Prostate cancer, transformation property, proliferation, micro-363,
      epithelial-to-mesenchymal transition.

PMID- 25591585
TI  - Autophagy facilitates multidrug resistance development through inhibition of
      apoptosis in breast cancer cells.
AB  - Acquired multidrug resistance (MDR) is the main mechanism of chemotherapeutic
      drugs resistance. Nevertheless, the mechanisms of MDR are complex and still not
      very clear. Recently, including our previous study, several studies have revealed
      that macroautophagy (here referred to as autophagy) induced by anti-cancer drugs
      in breast cancer cells may facilitate the development of resistance to epirubicin
      (EPI), paclitaxel (PTX), tamoxifen or herceptin. Whereas there are a few studies
      on the relationship between autophagy and MDR, especially the studies designed
      directly employing induced resistant breast cancer cells. Based on previous
      study, we explored the relationship between autophagy and MDR. The results showed
      that induced EPI-resistant MCF-7er and SK-BR-3er cells were simultaneously
      resistant to PTX and vinorelbine (NVB), which demonstrated that the cells
      obtained MDR phenotype. Furthermore, PTX and NVB could also induce autophagy in
      MCF-7er and SK-BR-3er cells, and the induced autophagy protected the cells from
      apoptosis, which facilitated the development of resistance to PTX and NVB. Thus,
      autophagy promoted the development of MDR in breast cancer cells through
      inhibition of apoptosis. In addition, we found that P-glycoprotein (Pgp) was
      overexpressed in MCF-7er and SK-Br-3er cells. And we preliminarily investigated
      the relationship between autophagy and P-glycoprotein (Pgp). The results showed
      that the expression of the protein did not obviously change despite the
      inhibition of autophagy. Therefore, the role of Pgp in the development of MDR
      might be independent of autophahy. Also this finding implies that autophagy might
      be a target to overcome MDR in breast cancer cells, and clinical use autophagy
      inhibitors might be one of the important strategies for overcoming MDR in breast
      cancer therapy. KEYWORDS: Autophagy, apoptosis, multidrug resistance, breast
      cancer, chemotherapy.

PMID- 25591586
TI  - Inhibitory effects of indirubin derivative PHII-7 on invasion and migration in
      metastatic cancer.
AB  - PHII-7, a derivative of indirubin, showed significant anti-cancer activities in
      vivo and in vitro. We asked whether treating human metastatic cancers and
      multidrug resistant cancer with PHII-7 would inhibit their invasion and
      migration. Cell growth was tested by MTT assay and colony formation assay.
      Apoptosis was examined by flow cytometry. Transwell-based assay and wound healing
      assay were used to examine cell invasion and migration. Real-time PCR assay and
      western blot assay were performed to test gene expression on mRNA and protein
      level, respectively. Firstly, we confirmed that MCF-7/ADR cells showed more
      invasive and migratory properties compared with MCF-7 cells which were associated
      with several EMT markers, such as E-cadherin, Slug and vimentin. Secondly, we
      found that slightly toxic doses of PHII-7 decreased the number of cells that
      invaded a model epithelial basement membrane and that migrated by switching the
      molecular signature of the cells from mesenchymal to epithelial. And PHII-7
      significantly regulated expression of several epithelial-mesenchymal transition
      (EMT)-related genes, including E-cadherin, Slug, beta-catenin and vimentin.
      Thirdly, compared with control, PHII-7 inhibited cell proliferation in a time-
      and dose-dependent manner. Higher doses of PHII-7 also induced apoptosis through
      activating PARP, caspase-9 and caspase-3. PHII-7 significantly inhibited invasion
      and migration in both metastatic cancers and multidrug resistant cancer. Our
      results may provide several data for future application of PHII-7 on drug design
      and patients treatment. KEYWORDS: PHII-7, invasion, migration, multidrug
      resistance, epithelial-mesenchymal transition.

PMID- 25591587
TI  - Autophagy inhibitor sensitizes MCF-7 breast cancer cells to novel cyclic
      tetrapeptide CTS203-induced caspase-9-dependent apoptotic cell death.
AB  - Histone deacetylase (HDAC) inhibitors have been demonstrated to be effective anti
      cancer candidates against aggressive malignancies. In previous study, a novel
      hydroxamic acid derivate, CTS203 (cyclo(-l-Asu(NHOH)-l-A3mc6c-l-Phe-d-Pro-)),
      demonstrated promising HDAC inhibitory activity. Herein, more biological
      evaluations including cell viability, cell cycle distribution, cellular
      morphology, expression quantification as well as protein-protein interactions
      were measured to investigate its cytotoxic mechanism. Corresponding with its
      significant HDAC inhibitory activity, CTS203 led to increased acetylation of
      H3K14, cell cycle arrest as well as consequent apoptotic cell death, with
      bearable influence on the viability of normal cells. However, schedule-dependent
      cytotoxicity against MCF-7 breast cancer cells revealed a delayed cellular
      response to chemo-stimuli. Within this corresponding period, autophagy was
      rapidly triggered once exposure started, whereas autophagy inhibitor sensitized
      MCF-7 cells to CTS203, exhibiting synergistically anti-proliferative effects. The
      expression variation in MCF-7 cells revealed that the cleavage of Beclin 1
      mediated by caspase-8 resulted in disabled autophagy, thus ultimately facilitated
      and fastened caspase-9-dependent apoptotic cell death. Taken together, these
      findings elucidated the mechanism of CTS203-induced cytotoxicity as well as
      suggested that appropriate manipulation of autophagy would be an adjunctive
      strategy to enhance HDAC inhibitor-induced cell death. KEYWORDS: cyclic
      tetrapeptide, apoptosis, autophagy, HDAC inhibitor, Beclin 1 cleavage.

PMID- 25591588
TI  - Genome-wide pathway analysis in glioma.
AB  - The aim of this study was to identify candidate single-nucleotide polymorphisms
      (SNPs) that may play a role in the susceptibility to glioma, to elucidate their
      potential mechanisms, and to generate SNP-to-gene-to-pathway hypotheses.A genome
      wide association study (GWAS) dataset of glioma including 509,345 SNPs from 1,856
      glioma patients and 4,955 control subjects of European descent was used in this
      study. Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was
      applied to the GWAS dataset.ICSNPathway analysis identified 6 candidate SNPs, 5
      genes, and 9 pathways, which revealed 5 hypothetical biological mechanisms. The
      hypothetical mechanisms, beginning with the strongest, are summarized as follows:
      (i) rs667128 alters the role of taste receptor, type 2, member 8 (TAS2R8) in
      taste receptor activity and taste transduction pathways (p < 0.001, false
      discovery rate (FDR) < 0.001; p = 0.001, FDR = 0.012, respectively), (ii)
      rs619381 modulates the effect of taste receptor, type 2, member 7 (TAS2R7) on
      taste receptor activity and taste transduction (p < 0.001, FDR < 0.001; p =
      0.001, FDR = 0.012), (iii) rs1033583 modulates delta-like protein 1 (DLL1),
      regulating cell adhesion and segment specification (p < 0.001, FDR = 0.011; p =
      0.001, FDR = 0.032), (iv) rs2232580 affects the role of lipopolysaccharide
      binding protein (LBP) in the response to lipopolysaccharide, positive regulation
      of interleukin-6 production, acute inflammatory response, and in macrophage
      activation (0.002 <= p <= 0.013; 0.012 <= FDR <= 0.030), and (v) rs4644 and
      rs4652 regulate lectin, galactoside-binding, soluble, 3 (LGALS3), affecting
      immunoglobulin binding (p = 0.010; FDR = 0.040).Using the ICSNPathway to analyze
      glioma GWAS data, 6 candidate SNPs, 5 genes (TAS2R8, TAS2R7, DLL1, LBP, and
      LGALS3), and 9 pathways that may contribute to the susceptibility of glioma were
      identified. KEYWORDS: glioma, genome-wide association study, pathway-based
      analysis.

PMID- 25591589
TI  - Pre- and post-operative evaluation: percentages of circulating myeloid-derived
      suppressor cells in rectal cancer patients.
AB  - This study aims to explore whether pre-operative or post-operative percentages of
      circulating myeloid-derived suppressor cells (MDSC) have any correlations with
      clinicopathological parameters in patients with rectal cancer and have any
      predictive values for local recurrence and disease free survival. Lin-/HLADR
      /CD11b+/CD33+ MDSCs were analyzed in the study. Blood samples before and after
      surgery were measured by flow cytometry to determine the MDSC percentages. Plasma
      arginase I levels were analyzed using an enzyme-linked immunosorbent assay.
      Digital rectal examination, abdominal ultrasonography, or computed tomography was
      performed every three months after surgery to monitor local recurrence. Prior to
      surgery, cancer patients presented with higher levels of circulating MDSC
      compared to healthy controls (medians of 3.89% and 0.57%, respectively). Seven
      days after operation, we observed an immediate increase in MDSC followed by a
      downtrend. Local recurrence was observed in 11 of 41 patients (26.8%) with stage
      I/II cancer and 11 of 23 patients (47.8%) with stage III cancer. Significantly
      higher percentages of MDSC were observed in patients who had local recurrence
      versus patients without local recurrence. Multivariate analysis further verified
      that the pre-operative level of MDSC was significantly associated with local
      recurrence (P=0.038). Therefore, our results indicate that pre-operative
      percentage of MDSC appears to be a reliable prognostic marker for local
      recurrence and poor disease free survival in rectal cancer patients with curative
      resection. KEYWORDS: myeloid-derived suppressor cells, rectal cancer, plasma
      arginase I, local recurrence, disease free survival.

PMID- 25591590
TI  - Clinical significance of microRNA-24 expression in esophageal squamous cell
      carcinoma.
AB  - microRNA-24 has been reported to participate in tumorgenesis and progression by
      several signaling pathways in various tumors. However, its potential as a serum
      diagnostic factor and predictive biomarker for esophageal squamous cell carcinoma
      (ESCC) has not been studied. In the present study, serum samples were collected
      from 105 pathologically proven ESCC patients and 30 healthy volunteers. All
      patients were treated with concurrent chemotherapy and radiotherapy. Real-time
      polymerase chain reaction was carried out to measure the serum miR-24 expression
      level in all patients and volunteers. The data were compared among radio
      sensitive group (CR+PR, 62 patients), radio-resistant group (SD+PD, 43 patients)
      and healthy volunteers to elucidate the diagnostic value of serum miR-24 testing
      for ESCC and the predictive value of miR-24 expression of treatment response. In
      the result, of the 105 ESCC patients enrolled in the study, 62 patients achieved
      partial or complete response. The serum miR-24 level in ESCC patients is 4.82
      times as high as that in healthy subjects(P<0.01), indicating that serum miR-24
      expression could be an excellent diagnostic factor. The mean miR-24 serum levels
      differ by 2.05 folds between radiosensitive group and radioresistant group,
      indicating that it may serve as a biomarker for predicting the response of ESCC
      patient to CRT. Furthermore, the responsiveness of therapy is significantly
      correlated with Cyfra21-1(P<0.05), serum miR-24 level (P<0.05) and the
      myelosuppression (P<0.01). In the prsent study, we come to the conclusion that
      serum miR-24 has the potential to serve as a noninvasive biomarker for both ESCC
      diagnosis and predicting treatment responses to concurrent chemo-radiation
      therapy. ESCC patients with lower Cyfra21-1, higher miR-24, and severer
      myelosupression were much more sensitive to CRT. KEYWORDS: miR-24 expression,
      esophageal squamous cell carcinoma, chemo-radiation therapy, radiosensitivity.

PMID- 25591591
TI  - Predictive factors for the presence of tumor cells in bone marrow and peripheral
      blood in breast cancer patients.
AB  - Simultaneous detection of disseminated tumor cells (DTCs) and circulating tumor
      cells (CTCs) was shown to be associated with an especially poor prognosis and
      increased incidence of disease-related deaths in non-metastatic breast cancer
      patients. We analyzed the occurance of DTCs and CTCs in patients with primary
      breast cancer and evaluated the correlation of their presence with other
      prognostic markers and investigated the changes in DTCs/CTCs number at different
      time points during treatment.Blood of 50 patients with primary breast cancer were
      used for immunomagnetic separation and detection of circulating tumor cells using
      the commercial available system the AdnaTest Breast CancerTM (AdnaGen GmbH,
      Langenhagen, Germany). Bone marrow aspirates from 50 patients were analyzed for
      DTCs by immunocytochemistry using the pan-cytokeratin antibody conjugated with
      FITC (Monoclonal Anti-Cytokeratin antibody F3418, Sigma Aldrich).DTCs were
      identified in 30% (15/50) and CTCs in 22% (11/50) of patients. We found that DTC
      positivity could point to a significantly high risk of larger primary tumor size
      (p-value 0.011) and significantly higher risk of lymph node involvement (p-value
      0.002). For CTC positivity, no such relationship was proven. DTCs have shown
      significantly higher prevalence in ER/PR-negative females and in HER2-positive
      cases. CTCs were equally prevalent in patients with the presence and absence of
      standard prognostic and predictive markers such as ER, PR and HER2. We found no
      correlation between CTCs and DTCs findings (r = -0.097, p = 0.504). We used
      DTCs/CTCs analysis for therapy monitoring in a small group of 29 patients, who
      underwent neoadjuvant chemotherapy (NACT). We find out no significant correlation
      between DTCs/CTCs detection and the primary tumor response to NACT. A pathologic
      complete response (pCR) was achieved by 31% (9/29) of the patients in our study,
      however, no association was observed between pCR and the detection of DTCs after
      NACT.These results support the use of DTCs/CTCs analysis in early breast cancer
      to generate clinically useful prognostic information. The study of these cells
      apart from the impact on refining prognosis, has the exciting potential of
      individualising treatment for women with breast cancer. KEYWORDS: breast cancer,
      disseminated tumor cells, circulating tumor cells, bone marrow aspiration,
      prognostic/predictive markers, therapy monitoring.

PMID- 25591592
TI  - MR-mammography - impact on disease extent determination and surgical treatment of
      invasive ductal and lobular breast cancers.
AB  - The aim of this study is to assess the impact of multiparametric MR imaging to an
      exact determination of the extent of invasive ductal and lobular breast cancers
      in routine clinical practice.180 women aged 27-74 years (median 52.4 years) with
      newly diagnosed invasive ductal and lobular breast cancers confirmed by core-cut
      or vacuum-assisted biopsy were examined by all three imaging modalities, i.e.
      digital X-ray mammography, ultrasonography and 3T MR-mammography. In case of MR
      mammography an extended protocol, i.e. combination of morphological breast MRI +
      DCE + DWI was used. For overall detection and determination of the extent of
      invasive breast cancers (IDC + ILC) MRmammography alone reached the diagnostic
      accuracy of 72.48%, while X-ray mammography 69.12% and ultrasonography 59.87%. In
      cases of ILC combination of X-ray mammography and MR- mammography with
      sensitivity of 96.15% was the most effective. In comparison with X-ray
      mammography and ultrasonography MR-mammography had higher sensitivity (96.15%,
      versus 90.28%) in the diagnosis of multifocal/ multicentric invasive lobular
      carcinoma and invasive ductal carcinoma with extensive intraductal component, as
      well. 3T MR-mammography is an effective complementary consulting modality to
      digital X-ray mammography and ultrasonography, and it is particularly beneficial
      in the detection of additional mammographically and ultrasonografically occult
      breast lesions, as well as in the determination of the real extent of
      pathological changes in the ipsilateral and contralateral breast. KEYWORDS: MR
      mammography, occult breast cancer, invasive ductal cancer, invasive lobular
      cancer, multifocality, multicentricity.

PMID- 25591593
TI  - Clinical significance of ERG rearrangement subtype and its association with
      increased p53 expression in Japanese and German prostate cancer.
AB  - This study investigated differences in prevalence of the androgen-regulated
      transmembrane protease serine 2 (TMPRSS2) and ETS transcription factor family
      member, v-ets erythroblastosis virus E26 oncogene homolog (ERG) fusion gene
      (TMPRSS2-ERG fusions) in clinically localized prostate cancer Japanese and German
      patients. A total of 105 specimens, including 69 Japanese and 36 German patients,
      were collected. The status of TMPRSS2-ERG fusion was determined by fluorescence
      in situ hybridization, and correlations of the TMPRSS2-ERG fusion with
      clinicopathological characteristics and immunohistochemistry were studied. Gene
      fusions were identified in 20% (14/69) of Japanese and 53% (19/36) of German
      patients (P < 0.001). The difference in the type of gene fusion between the two
      ethnic groups was statistically significant (P=0.024). Overexpression of ERG
      protein was significantly associated with gene fusion. Biochemical recurrence was
      significantly higher in patients with ERG overexpression than in those without,
      and not related to TMPRSS2-ERG fusion status. Interestingly, two types of gene
      fusions (deletion and increase of copy number) were significantly associated with
      increased p53 expression (P = 0.005). Association of specific gene fusions
      harboring higher genomic alterations with p53 expression levels suggests that p53
      mutation might drive more aggressive arrangements of TMPRSS2-ERG fusion in
      prostate cancer. KEYWORDS: ERG, p53, prostate cancer, TMPRSS2-ERG fusion.

PMID- 25591594
TI  - Decreased bone mineral density and alteration in biochemical bone metabolism
      markers in children affected by bone tumors after completion of therapy.
AB  - The aim of this study was to assess bone mineral density (BMD) and biochemical
      bone metabolism markers in patients with bone tumors after anti-cancer treatment.
      The study included 27 patients (median age 15 years) with malignant bone tumors
      and 27 healthy children. In all subjects, BMD and body composition were measured
      by dual-energy x-ray absorptiometry. Serum bone markers were determined by
      immunoenzymatic assays. After completion of treatment, patients with bone tumors
      had significantly decreased total and lumbar spine BMD. We observed lower calcium
      and vitamin D levels in patients and comparable values of bone turnover markers
      (carboxyterminal telopeptide of collagen type I - CTX, bone alkaline phosphatase 
      BALP and osteocalcin - OC) in both groups of children. However, the level of
      carboxylated osteocalcin (cOC) was significantly lower (p<0.01) and
      undercarboxylated OC (ucOC) was higher (p<0.05) in patients than in controls.
      Additionally, we observed similar values of anthropometric parameters in the
      subgroups of patients treated with methotrexate (MTX) or without MTX. In patients
      treated without MTX we found lower (p<0.05) ratio of cOC/ucOC, lower vitamin D
      level and higher CTX concentrations. Patients with bone tumors after anticancer
      treatment had decreased bone mineral density and alterations in bone metabolism
      markers with potential decrease in bone formation. KEYWORDS: bone cancer
      survivors, bone mineral density, bone formation markers, bone resorption markers,
      methotrexate.

PMID- 25591595
TI  - Comparison of 18F-FDG PET/CT and MDCT for staging/restaging of non-small cell
      lung cancer.
AB  - Multi-detector computed tomography (MDCT) is most commonly used for staging of
      non-small cell lung cancer (NSCLC). In recent years, 18F- fluorodeoxyglucose
      positron emission tomography combined with computed tomography (18F-FDG PET/CT)
      has also been used for the same purpose. Since studies comparing these two
      methods are scarce, our aim was to determine how the TNM classification and
      thereby staging of NSCLC compare between 18F-FDG PET/CT and MDCT. 18F-FDG PET/CT
      and MDCT were collected in 83 patients with NSCLC 3 to 30 days apart (median 17
      days). The investigators interpreting 18F-FDG PET/CT were unaware of MDCT
      results. The Cohen's kappa (kappa) was calculated to determine the rate of
      agreement. The hypothesis was that the strength of agreement between the two
      methods will be at least moderate (kappa>0.40) based on the adopted criteria
      (kappa<0.20 poor; 0.21-0.40 fair; 0.41-0.60 moderate; 0.61-0.80 good; 0.81-1.00
      very good agreement). The agreement was moderate for determining the T class
      (kappa=0.45, overall agreement 58%), poor for the N class (kappa=0.13, 42%) and
      fair for the M class (kappa=0.22, 58%). The agreement for overall staging of
      NSCLC was poor (kappa=0.20, 45%). The major source of disagreement was that
      metastases were present more frequently and/or in larger number on 18F-FDG PET/CT
      than MDCT in the contralateral mediastinal, supraclavicular, and distant lymph
      nodes, as well as in the bones and suprarenal glands. Since 18F-FDG PET/CT
      detected more regional and distant metastases than MDCT, we conclude that FDG
      PET/CT is useful for staging/restaging and planning treatment of patients with
      NSCLC. KEYWORDS: Non-small cell lung cancer, positron emission tomography,
      multidetector computed tomography, metastases detection.

PMID- 25591596
TI  - Gefitinib maintenance therapy in Chinese advanced-stage lung adenocarcinoma
      patients with EGFR mutations treated with prior chemotherapy.
AB  - The aim of this study was to determine the response of advanced-stage non-small
      cell lung cancer (NSCLC) patients with or without EGFR mutations to platinum
      based chemotherapy with or without gefitinib maintenance. Patients were treated
      with four cycles of platinum-based chemotherapy. Patients with wild-type EGFR
      were observed (group 1; n=15). EGFR mutation-positive patients were randomly
      assigned to observation (group 2; n=7) or gefitinib maintenance (group 3; n=7).
      The median patient age was 59 years. The 1-year progression-free survival rates
      in groups 1, 2, and 3 were 6.7%, 28.6%, and 57.1%, respectively (p = 0.049); the
      1-year overall survival rates were 53.3%, 57.1 %, and 100%, respectively (p =
      0.111). The results indicate that patients with advanced-stage NSCLC with EGFR
      mutations have a better response to chemotherapy followed by gefitinib than
      chemotherapy alone and a better response to chemotherapy than wild-type patients.
      KEYWORDS: chemotherapy, gefitinib, NSCLC, tyrosine kinase inhibitors.

PMID- 25591597
TI  - Impact of risk factors on prevalence of anal HPV infection in women with
      simultaneous cervical lesion.
AB  - The aim of our study was to determine the risk factors associated with anal HPV
      infection in HIV-negative women with high-grade cervical lesion. The study group
      included 172 "high-risk" women who underwent conization for high-grade cervical
      intraepithelial lesion or microinvasive cervical cancer (CIN 2+). The control
      group consisted of 100 "low-risk" women with non-neoplastic gynecologic diseases.
      All participants completed a questionnaire detailing medical history and sexual
      risk factors and were subjected to anal and cervical HPV genotyping. Concurrent
      cervical and anal HPV infections were detected in 42.4% (73/172) women of the
      study group, and in 8.0% (8/100) of women in the control group, respectively. The
      subgroup with concurrent HPV infections (n=73) dominated women with CIN 3 and
      microinvasive cancer and anal HPV 16 infections (n=53). Women with concurrent
      infections more frequently reported any type of sexual contact with the anus
      including non-penetrative anal sex (OR 2.62, p=0.008). Reporting >5 lifetime
      sexual partners (OR 2.43, p=0.041), smoking > 60 cigarettes per week (OR 2.33,
      p=0.048), and a history of penetrative anal intercourse (OR 3.87, p=0.002) were
      observed as the significant risk factors in women with multiple concurrent HPV
      infections. Our data support anal HPV testing and anal Pap smear screening in all
      women with severe cervical lesions caused by HPV 16 and a history of any sexual
      contact with the anus, heavy smoking and/or more than 5 lifetime sexual partners.
      KEYWORDS: anal cancer, cervical intraepithelial neoplasia, HPV, risk factor.

PMID- 25591598
TI  - Assessing the interactions between the associations of common genetic variants on
      2q35 and 16q12 with breast cancer risk.
AB  - Genome-wide association studies (GWAS) have identified 2q35 and 16q12 as breast
      cancer (BC) susceptibility loci. However, the association between the two
      polymorphisms and BC remains controversial and inconsistent. We therefore
      performed a more precise estimation of these relationships by meta-analysing the
      currently available evidence from the literature. The PubMed, Ovid, Medline and
      Web of Science databases were searched. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strengths of the associations.
      Thirty studies, including 106,312 cases and 140,939 controls, were identified.
      Overall, significantly elevated breast cancer risk was associated with the A
      allele of 2q35 rs13387042 when all studies were pooled into the meta-analysis (OR
      1.11, 95%CI 1.07-1.15). Additionally, the T allele of 16q12 rs3803662 was
      associated with significantly increased breast cancer risk (OR 1.20, 95%CI 1.16
      1.24). When stratifying for ethnicity, significantly increased risks were found
      among Caucasians, Asians and mixed ethnicities for both rs13387042 and rs3803662.
      For rs13387042, an association was observed for both oestrogen receptor-positive
      (ER+) (OR 1.14, 95%CI 1.11-1.17) and ER-negative (ER-) disease (OR 1.05, 95%CI
      1.01-1.09) and for progesterone receptor-positive (PR+) (OR 1.16, 95%CI 1.12
      1.19) and PR-negative (PR-) disease (OR 1.07, 95%CI 1.03-1.12). Similarly, a
      stronger association was observed for rs3803662 with ER+ tumors (OR 1.23, 95%CI
      1.13-1.32) compared with ER- tumors (OR 1.08, 95%CI 0.97-1.20), and the same
      condition occurred for the polymorphism with PR+ tumors (OR 1.26, 95%CI 1.02
      1.55) versus with PR- tumors (OR 1.15, 95%CI 0.90-1.46). When stratified by BRCA
      mutation status, a stronger association was observed with BRCA2 carriers (OR
      1.23, 95%CI 1.05-1.44) than BRCA1 carriers (OR 1.09, 95%CI 1.04-1.15). In
      conclusion, this meta-analysis demonstrated that the A allele of 2q35 rs13387042
      and the T allele of 16q12 rs3803662 are risk factors associated with increased
      breast cancer susceptibility. KEYWORDS: rs13387042, rs3803662, oestrogen
      receptor, progesterone receptor, breast cancer, meta-analysis.

PMID- 25591599
TI  - Daily image-guidance in prostate cancer radiotherapy - implications for treatment
      margins.
AB  - Our purpose was to evaluate interfractional organ and patient movement during
      radiotherapy of prostate cancer and to calculate the necessary CTV to PTV
      margins. Fifty patients irradiated between 2009 and 2011were included into the
      prospective study. The 2D-2D KV system combined with the intraprostatic fiducial
      marker were used for daily position verification. Based on the 8629 measurements
      of isocentre displacement an interfractional motion of pelvis and prostate was
      evaluated. The CTV to PTV margins were calculated. Margins of 0.7 cm (AP), 1 cm
      (SI) and 0.35 cm (LR) are necessary when only bony based IGRT is performed.
      Margins of 1.0 cm, 1.8 cm and 0.5 cm in AP, SI and LR directions respectively are
      necessary in case of no IGRT.There was no clinically relevant changes in
      patient/target mobility throughout the whole treatment. The IGRT is essential for
      state of art radiotherapy of prostate cancer. Necessary CTV to PTV margins are
      much bigger in case of no IGRT performed. Changing of margins size throughout
      regular treatment is not necessary. KEYWORDS: IGRT, prostate cancer, fiducial
      marker.

PMID- 25591600
TI  - Elevated Farnesoid X Receptor (FXR) and Retinoid X Receptors (RXRs) expression is
      associated with less tumor aggressiveness and favourable prognosis in patients
      with pancreatic adenocarcinoma.
AB  - Farnesoid X Receptor (FXR) and its co-partners Retinoid X Receptors (RXRs) are
      considered to participate in crucial biochemical and cellular processes, being
      involved in the pathogenesis of several diseases, including cancer. The present
      study aimed to evaluate the clinical significance of FXR alone and in conjunction
      with RXRs expression, in pancreatic adenocarcinoma. FXR, RXR-alpha, -beta and 
      gamma protein expression was assessed immunohistochemically on tumoral samples of
      55 pancreatic adenocarcinoma cases and was statistically analyzed with
      clinicopathological characteristics, tumor proliferative capacity and patients'
      survival. Enhanced FXR expression was borderline associated with earlier
      histopathological stage (p=0.054). Concomitant elevated FXR/RXR-alpha expression
      was significantly associated with decreased tumor histological grade (p=0.017),
      while concomitant enhanced FXR/RXR-beta and FXR/RXR-gamma expression with earlier
      histopathological stage (p=0.017 and p=0.004, respectively) and smaller tumor
      size (p=0.037 and p=0.005, respectively). Concomitant enhanced FXR/RXR-gamma
      expression was additionally significantly associated with the absence of lymph
      node metastases (p=0.018). Pancreatic adenocarcinoma patients with enhanced FXR,
      FXR/RXR-beta or -gamma expression showed significantly longer survival times
      compared to those with low expression (p=0.013, p=0.021 and p<0.001,
      respectively). In multivariate analysis, FXR and FXR/RXR-gamma expression were
      identified as independent prognostic factors (p=0.044 and p=0.001, respectively).
      CONCLUSION: The present study suggested that FXR and RXRs were implicated in
      pancreatic malignant disease progression, reinforcing their utility as clinical
      markers for patients' management and prognosis, as well as targets for potential
      therapeutic interventions. KEYWORDS: FXR, RXR, pancreatic adenocarcinoma,
      immunohistochemistry, clinicopathological parameters, patients' survival.

PMID- 25591601
TI  - Performance management systems and the reality of Canadian Healthcare
      Organizations - from industrial to learning models.

PMID- 25591602
TI  - End-of-life hospital care for cancer patients: an update.
AB  - Cancer is the leading cause of death in Canada, and the number of new cases is
      expected to increase as the population ages and grows. This study examined the
      use of hospital services in the last month of life by adult cancer patients who
      died in Canadian acute care hospitals in fiscal year 2012-2013. Almost 25,000
      Canadian cancer patients - excluding those in Quebec - died in acute care
      hospitals, representing approximately 45% of the estimated cancer deaths in 2012
      2013. The proportion of in-hospital deaths varied across jurisdictions. Twenty
      three percent of these patients were admitted to acute care multiple times in
      their last 28 days of life, with a higher percentage for rural (29%) compared to
      urban (21%) patients. Relatively few patients used intensive care units or
      received inpatient chemotherapy in their last 14 days of life. 

PMID- 25591603
TI  - Primary care of adults with developmental disabilities in Ontario.
AB  - The health status and healthcare of adults with developmental disabilities have
      not been well-studied in Ontario, due to the absence of population-based data. To
      address this deficit, the Health Care Access Research and Developmental
      Disabilities (H-CARDD) program - a provincial partnership of scientists,
      policymakers and clinicians - has used existing provincial-level administrative
      data to provide descriptive information on the health of adults with
      developmental disabilities and the quality of their primary care relative to
      other adults. H-CARDD's findings have revealed many gaps in the care of adults
      with developmental disabilities. While primary care providers are critical to
      achieving needed changes, the broader healthcare context and infrastructure also
      need to be considered. 

PMID- 25591604
TI  - In conversation with Darrell Bricker.

PMID- 25591605
TI  - Special focus on family caregiving.

PMID- 25591606
TI  - Caring for caregivers of high-needs older persons.
AB  - The Caregiver Framework for Seniors Project (CFSP) is led by the Alzheimer
      Society of Toronto in partnership with the Toronto Central Community Care Access
      Centre and six community support service agencies. This ground-breaking
      initiative aims to increase caregiver resiliency and capacity to continue to
      provide care through a platform of supports. In the CFSP, care coordinators
      negotiate flexible support packages in consultation with caregivers to meet their
      self-reported needs and the needs of care recipients. This paper presents the
      findings from a multi-stage, mixed-methods formative evaluation of the CFSP. 

PMID- 25591607
TI  - Caring for caregivers of high-needs children.
AB  - The Caregiver Framework for Children with Medical Complexity, led by the Hospital
      for Sick Children, is a ground-breaking initiative that validates and supports
      the vital role of unpaid, family caregivers. The project uses a supported self
      management model that includes a modest amount of funding to address pressing
      needs, and relies on Key Workers who provide ongoing education, counselling and
      care management to assist caregivers in planning over the longer-term. This paper
      describes the findings from a multi-stage, mixed-methods evaluation to examine
      the design and outcomes of the Caregiver Framework. 

PMID- 25591608
TI  - Caregiving is not a disease: moving from reactive to proactive supports for
      family caregivers across the healthcare system.
AB  - Saint Elizabeth partnered directly with family caregivers in a study to develop
      promising practices and indicators of effective caregiver education and support.
      Researchers heard that caregivers want and need proactive supports to help them
      thrive and equip them with tools and resources to protect their capacity to care
      and prevent distress; however, the current system of support is heavily focused
      on a reactive, medical approach to managing and treating caregiver "burden."
      Saint Elizabeth is dedicated to promoting a philosophical shift in thinking about
      caregiver education and support and is actively re-designing support services to
      reflect what caregivers say they need. 

PMID- 25591609
TI  - The safety at home study: an evidence base for policy and practice change.
AB  - This paper explores the policies and practices that are needed to improve the
      safety of home care in light of the most recent evidence about home care safety
      in Canada. Four areas for policy and practice change are addressed: 1) the
      promotion of effective communication processes in home care through cross-sector
      collaboration, case management and technology innovations; 2) screening for
      safety risk factors; 3) standardizing care processes, packaging and equipment;
      and 4) supporting family/caregivers and strengthening clients' ability to engage
      in therapeutic self-care. Evidence-based strategies for change are presented
      within the context of the evidence about home care safety issues. 

PMID- 25591610
TI  - A novel community-based model to enhance health promotion, risk factor management
      and chronic disease prevention.
AB  - Chronic disease is a highly expensive but preventable problem to the healthcare
      system. Evidence suggests that impacting modifiable behaviours and risk
      management factors in the areas of physical inactivity, unhealthy diet, stress
      and obesity can alleviate the burden of chronic disease problem to a large
      extent. Despite this recognition, the challenge is embedding these recognized
      priorities into the community and in primary care in a sustainable and meaningful
      manner. Primary Health Care in Capital Health responded to this challenge by
      developing and implementing a free, interprofessional and community-based
      service, namely, the Community Health Teams (CHTs), that offers health and
      wellness, risk factor management, wellness navigation and behaviour-based
      programming. In this paper, the development and implementation of the CHTs are
      discussed. Preliminary outcomes for the model are significant and promising.
      Formal and large-scale studies are planned to validate these outcomes with
      additional research rigour. 

PMID- 25591611
TI  - Innovative model of interprofessional geriatric consultation: specialized seniors
      clinics.
AB  - As the Canadian population ages, healthcare systems have become increasingly
      interested in exploring new ways to deliver services to frail older adults, and
      in particular older adults with dementia. The Specialized Seniors Clinics (SSCs)
      are an innovative integrated network of six outpatient clinics in BC's Fraser
      Health Authority that utilize interprofessional teams to provide comprehensive
      geriatric assessments and care planning for frail older adults. The SSCs provided
      approximately 19,000 appointments in the past fiscal year, and clients and
      primary care physicians are highly satisfied with the model. This article
      describes the SSC model and provides reflection on the model development,
      implementation and standardization processes. 

PMID- 25591612
TI  - Integrated client care for frail older adults in the community: preliminary
      report on a system-wide approach.
AB  - The Toronto Central Community Care Access Centre is leading a collaborative local
      health integration network systemic change initiative to implement and evaluate a
      practical model of integrated care for older adults with complex needs. The
      approach is embedded in the community where older adults and their families live
      and is designed to first and foremost improve the quality of care while
      ultimately bending the cost curve. The model is leveraging and aligning existing
      system resources by bringing together sectors from across the health system to
      create ways of working that build capacity in the system to be more responsive to
      this population. Outcomes to date will be discussed and next steps described. The
      secondary goal was to understand the key elements of this integration that can be
      scaled locally and across the province. 

PMID- 25591613
TI  - Patient and community engagement: the approach at university health network.
AB  - In the past few years, all of us in healthcare have heard phrases such as
      "patient engagement," "community engagement," "stakeholder engagement," "patient
      feedback," "community involvement," "patients as partners in care," "patient
      centred care," "patient experience" and "patient involvement in healthcare."
      These phrases (and many more that have not been identified) speak to a process
      whereby those people who have a legitimate and meaningful relationship with the
      healthcare organization and its providers should be involved in a meaningful
      discourse and set of transactions with the organization and the providers. If
      involvement doesn't happen naturally, then there is a sense that some sort of
      definitive outreach should occur that will engage and enroll meaningful
      involvement in a variety of ways. 

PMID- 25591614
TI  - Principles of rehabilitation and reactivation.
AB  - Skeletal muscle dysfunction and physical inactivity are two clinically important
      features of a wide range of acute and chronic respiratory conditions.
      Optimisation of both of these features is important in order to improve physical
      function, prevent clinical deterioration and maximise community participation.
      One of the most potent and evidence-based interventions to address these physical
      deficits is pulmonary rehabilitation (PR). Whilst the majority of PR research has
      been conducted in patients with chronic obstructive pulmonary disease, there is
      widespread recognition that PR can benefit many other respiratory patient groups.
      These include patients with interstitial lung diseases, asthma, pulmonary
      hypertension, pre-/post-lung surgery (e.g. lung cancer, transplantation) and
      cystic fibrosis to name a few. Exercise training must be appropriately prescribed
      by a skilled healthcare professional with comprehensive knowledge of the
      pathology and physiology of these conditions, as well as a sound understanding of
      the exercise physiology and core principles of exercise prescription, monitoring
      and progression. It has also become increasingly recognised that people with
      respiratory conditions, particularly those with chronic disease, are considerably
      less active than those of good health. PR should therefore aim to induce
      behavioural change to facilitate the adoption and maintenance of an active
      lifestyle. In addition, PR should pay attention to the psychological well-being
      of patients and self-management of their lung disease in all its aspects. To that
      end, multidisciplinary individualised programs should be offered. This review
      sets the scene of PR principles for a series of papers that will focus on
      specific diseases other than chronic obstructive pulmonary disease where
      rehabilitation may offer a clinically important aspect of care over and above
      conventional pharmacological treatment.

PMID- 25591615
TI  - Bilateral cervical fistulas from heterotopic salivary gland tissues.
AB  - A 24-year-old male was referred to our department with intermittent clear
      drainage in both sides of the middle neck that did not increase while eating. On
      physical examination, there were fistulas in both sides of the neck, anterior to
      the sternocleidomastoid muscles. Fistulography revealed a 9-mm-long sinus from
      the left fistula, extending in the medial-caudal direction. On the right side,
      cannulation was not possible. Surgical excision of the lesion was performed on
      both sides, and the pathological examination revealed heterotopic salivary gland
      tissue (HSGT). From a literature review of reports of bilateral neck HSGT, we
      found that it is often associated with a family history of HSGT and other
      congenital anomalies. However, our case was different from the previously
      reported cases in that, although it was a bilateral case, it lacked any family
      history of HSGT or other congenital anomalies. Clinicians should include HSGT in
      the differential diagnosis of neck sinuses. (c) 2015 S. Karger AG, Basel. 

PMID- 25591616
TI  - Comprehensive DNA Methylation and Extensive Mutation Analyses of HER2-Positive
      Breast Cancer.
AB  - OBJECTIVE: Resistance to trastuzumab is a problem that remains to be solved in
      HER2-positive breast cancer. We aimed to characterize profiles of genetic and
      epigenetic alterations in cancer-related pathways in HER2-positive breast
      cancers, using biopsy tissue samples obtained from patients enrolled in a
      prospective neoadjuvant clinical trial. METHODS: HER2-positive breast cancer
      tissue samples were collected and processed with the PAXgene Tissue System. A
      total of 24 breast cancers were analyzed. Genetic alterations of 409 cancer
      related genes were analyzed by a bench-top next-generation sequencer. DNA
      methylation statuses were analyzed by a bead array with 485,512 probes. RESULTS:
      The WNT pathway was potentially activated by aberrant methylation of its negative
      regulators, such as DKK3 and SFRP1, in 9 breast cancers. The AKT/mTOR pathway was
      activated by mutations of PIK3CA in 5 breast cancers. The Notch pathway was
      potentially activated by mutations of NOTCH1 and NOTCH2 in 4 breast cancers. The
      p53 pathway was inactivated by mutations of TP53 in 13 breast cancers and
      potentially by aberrant methylation of its downstream genes in 10 breast cancers.
      Cell adhesion was affected by mutations of CDH1 in 1 breast cancer. CONCLUSION:
      Genes involved in cancer-related pathways were frequently affected not only by
      genetic but also by epigenetic alterations in HER2-positive breast cancer.

PMID- 25591617
TI  - The effects of a novel calcium-free lactate buffered dialysis and substitution
      fluid for regional citrate anticoagulation--prospective feasibility study.
AB  - BACKGROUND: Testing metabolic effects of a novel calcium-free, magnesium,
      phosphate and lactate containing solution (Lactocitrate) in combination with
      citrate anticoagulation. METHODS: Patients on CRRT (2,000 ml/h, blood flow (Qb)
      100 ml/min, trisodium citrate (4% TSC)) with arterial lactate <3 mmol/l were
      included. At start, bicarbonate-buffered fluid was changed to Lactocitrate and
      the substitution of magnesium and phosphorus ceased. At 9 h the Qb was increased
      to 150 ml/min. At 18 h the CRRT dosage was increased to 3,000 ml/h. RESULTS: In
      22 CVVHDF patients and another 23 on CVVH the pH, aHCO3 and Na (all p > 0.05)
      showed no significant changes regardless of the increased dosage of 4% TSC at 9 h
      (p < 0.001). Mgtot and phosphorus stabilised within normal range. Arterial
      lactate increased to 1.9 (1.6-2.6) mmol/l at 3,000 ml/h, p < 0.001). Citrate- and
      lactate-related energetic gains were up to 74 (61-86) kJ/h. CONCLUSIONS: The
      fluid performed well within ordinary CRRT dosage and Qb up to 150 ml/min. Lactate
      levels mildly increased and no magnesium and phosphorus replenishments were
      necessary.

PMID- 25591619
TI  - New coronavirus outbreak. Lessons learned from the severe acute respiratory
      syndrome epidemic.
AB  - System dynamics approach offers great potential for addressing how intervention
      policies can affect the spread of emerging infectious diseases in complex and
      highly networked systems. Here, we develop a model that explains the severe acute
      respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in Hong Kong
      in 2003. The dynamic model developed with system dynamics methodology included 23
      variables (five states, four flows, eight auxiliary variables, six parameters),
      five differential equations and 12 algebraic equations. The parameters were
      optimized following an iterative process of simulation to fit the real data from
      the epidemics. Univariate and multivariate sensitivity analyses were performed to
      determine the reliability of the model. In addition, we discuss how further
      testing using this model can inform community interventions to reduce the risk in
      current and future outbreaks, such as the recently Middle East respiratory
      syndrome coronavirus (MERS-CoV) epidemic. 

PMID- 25591620
TI  - Characterization of two temperate Lactobacillus paracasei bacteriophages:
      morphology, kinetics and adsorption.
AB  - BACKGROUND/AIMS: Adsorption and kinetic parameters, latent period, burst size and
      burst time, are characteristics of phage/host systems and can be affected by
      several environmental factors. As only few studies have focused on temperate
      dairy phages, we characterized these parameters on temperate Lactobacillus
      paracasei phages Phi iLp84 and Phi iLp1308, infective for probiotic strains.
      METHODS: Phages were characterized by transmission electron microscopy and
      genomic DNA restriction. Adsorption under different environmental conditions,
      phage kinetics and efficiency of plating (EOP) were determined using the double
      layer titration method. RESULTS: Phages Phi iLp84 and Phi iLp1308 belong to the
      Siphoviridae family and have genome sizes of 38 and 34 kbp, respectively.
      Adsorption was affected by calcium concentration, pH, temperature and host
      viability, and reached a limit at very high multiplicity of infection. Latency,
      burst time and burst size were of 85 min, 131 min and 46 for Phi iLp84, and 51
      min, 92 min and 28 for Phi iLp1308, respectively, at 37 degrees C. A clear
      influence of temperature on phage kinetics was observed. Regarding EOP, Phi iLp84
      produced plaques on only 1 out of 8 strains tested. CONCLUSION: Noticeable
      differences in adsorption, kinetics and EOP were found for two morphologically
      identical temperate L. paracasei phages of similar origin.

PMID- 25591621
TI  - Hypoxia disrupts the expression levels of circadian rhythm genes in
      hepatocellular carcinoma.
AB  - Disturbance in the expression of circadian rhythm genes is a common feature in
      certain types of cancer, however the mechanisms mediating this disturbance remain
      to be elucidated. The present study aimed to investigate the effect of hypoxia on
      the expression of circadian rhythm genes in liver cancer cells and to identify
      the mechanisms underlying this effect in hepatocellular carcinoma (HCC). The HCC
      cell line, PLC/PRF/5. was treated with either a vehicle control or CoCl2 at 50,
      100 or 200 uMU for 24 h. Following treatment, the protein expression levels of
      hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha were detected by western
      blotting and the mRNA expression levels of circadian rhythm genes, including
      circadian locomotor output cycles kaput (Clock), brain and muscle Arnt-like 1
      (Bmal1), period (Per)1, Per2, Per3, cryptochrome (Cry)1, Cry2 and casein kinase
      Iepsilon (CKIepsilon), were detected by reverse transcription quantitative
      polymerase chain reaction (RT-qPCR). Expression plasmids containing HIF-1alpha or
      HIF-2alpha were transfected into the PLC/PRF/5 cells using liposomes and RT-qPCR
      was used to determine the effects of the transfections on the expression levels
      of circadian rhythm genes. Following treatment with CoCl2, the protein expression
      levels of HIF-1alpha and HIF-2alpha were upregulated in a CoCl2 concentration
      dependent manner. The mRNA expression levels of Clock, Bmal1 and Cry2 were
      increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and
      CKIepsilon were decreased following CoCl2 treatment (P<0.05). In the PLC/PRF/5
      cells transfected with the plasmid containing HIF-1alpha, the mRNA expression
      levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of
      Per1, Per2, Per3, Cry1 and CKIepsilon were decreased. In the PLC/PRF/5 cells
      transfected with the plasmid containing HIF-2alpha, the mRNA expression levels of
      Clock, Bmal1, Per1, Cry1, Cry2 and CKIepsilon were upregulated, and the mRNA
      expression levels of Per2 and Per3 were downregulated (P<0.05). A hypoxic
      microenvironment may contribute to the disturbance in the expression of circadian
      genes in HCC. HIF-1alpha and HIF-2alpha are involved in this process and have
      redundant, but not identical effects.

PMID- 25591618
TI  - Genetic and environmental factors associated with vitamin B12 status in Amazonian
      children.
AB  - OBJECTIVE: To evaluate the prevalence of vitamin B12 deficiency and factors
      associated with vitamin B12 status in Amazonian children. DESIGN: Genetic risk
      score (GRS), socio-economic and nutritional status, and morbidity data were the
      independent variables used in multiple linear regression models to evaluate
      factors associated with vitamin B12 status in a population-based cross-sectional
      study. GRS was created by summing a number of known risk alleles for low serum
      vitamin B12. SETTING: Acrelandia, western Brazilian Amazon. SUBJECTS: Children (n
      988) aged <10 years. RESULTS: Overall prevalence of vitamin B12 deficiency (<150
      pmol/l) was 4.2 (95 % CI 3.0, 5.6) % and was highest in children aged <24 months:
      13.6 (95 % CI % 8.8, 19.7) %. For children <24 months, wealth index (beta=0.017,
      P=0.030) and animal protein intake (beta=0.219, P=0.003) were positively
      associated with vitamin B12 status. GRS (beta=-0.114, P<0.001) and serum
      homocysteine (beta=-0.049, P<0.001) were negatively associated. Among children
      aged >=24 months, vitamin B12 status was positively associated with wealth index
      (beta=0.012, P<0.001), height-for-age Z-score (beta=0.024, P=0.033) and serum
      vitamin A (beta=0.089, P<0.001). Age>=60 months (beta=-0.118, P<0.001), GRS
      (beta=-0.048, P<0.001), maternal schooling <5 years (beta=-0.083, P<0.001), low
      intake of animal-derived foods (beta=-0.050, P=0.030), serum homocysteine (beta=
      0.053, P<0.001), serum folate >=23.6 nmol/l (beta=-0.055, P=0.012) and
      geohelminth infection (beta=-0.141, P=0.017) were negatively associated with
      vitamin B12 status. CONCLUSIONS: GRS, poverty, low intake of animal-derived
      foods, geohelminth infection, vitamin A and folate status were important factors
      associated with vitamin B12 status of children in our study.

PMID- 25591622
TI  - Edge effects on morphometrics and body mass in two sympatric species of mouse
      lemurs in Madagascar.
AB  - Edge effects are an inevitable and important consequence of forest loss and
      fragmentation. These effects include changes in species biology and biogeography.
      Here we examine variations in body mass and morphometrics for 2 sympatric species
      of mouse lemurs (Microcebus murinus and M. ravelobensis) between edge and
      interior habitats in the dry deciduous forest at Ankarafantsika National Park.
      Between May and August 2012, we conducted mark-recapture experiments on mouse
      lemurs trapped along edge and interior forest transects within continuous forest
      adjacent to a large savannah. Of the 34 M. murinus captured during our study, 82%
      (n = 28) were trapped in interior habitats. Conversely, 72% (n = 47) of M.
      ravelobensis were captured in edge habitats. We found that mean body mass of M.
      murinus and M. ravelobensis did not differ between edge and interior habitats.
      However, female M. ravelobensis weighed significantly more in edge habitats
      (56.09 +/- 1.74 g) than in interior habitats (48.14 +/- 4.44 g). Our study
      provides some of the first evidence of sex differences in edge responses for a
      primate species.

PMID- 25591623
TI  - Current immunological and molecular tools for leptospirosis: diagnostics, vaccine
      design, and biomarkers for predicting severity.
AB  - Leptospirosis is a zoonotic spirochaetal illness that is endemic in many tropical
      countries. The research base on leptospirosis is not as strong as other tropical
      infections such as malaria. However, it is a lethal infection that can attack
      many vital organs in its severe form, leading to multi-organ dysfunction syndrome
      and death. There are many gaps in knowledge regarding the pathophysiology of
      leptospirosis and the role of host immunity in causing symptoms. This hinders
      essential steps in combating disease, such as developing a potential vaccine.
      Another major problem with leptospirosis is the lack of an easy to perform,
      accurate diagnostic tests. Many clinicians in resource limited settings resort to
      clinical judgment in diagnosing leptospirosis. This is unfortunate, as many other
      diseases such as dengue, hanta virus, rickettsial infections, and even severe
      bacterial sepsis, can mimic leptospirosis. Another interesting problem is the
      prediction of disease severity at the onset of the illness. The majority of
      patients recover from leptospirosis with only a mild febrile illness, while a few
      others have severe illness with multi-organ failure. Clinical features are poor
      predictors of potential severity of infection, and therefore the search is on for
      potential biomarkers that can serve as early warnings for severe disease. This
      review concentrates on these three important aspects of this neglected tropical
      disease: diagnostics, developing a vaccine, and potential biomarkers to predict
      disease severity. 

PMID- 25591624
TI  - Endometriosis and perceived stress: impact of surgical and medical treatment.
AB  - BACKGROUND: The aim of the study was to investigate the levels of perceived
      stress in a group of women with a long-term history of endometriosis in
      conjunction with surgical and/or medical treatments. METHODS: A clinical trial
      was conducted at the Department of Molecular and Developmental Medicine,
      University of Siena, in collaboration with a non-profit association of women with
      endometriosis, A.P.E. Onlus. Patients (n = 204) with a previous diagnosis of
      endometriosis (for at least 3 years) were included in this study. Each patient
      completed a semi-structured questionnaire and a validated scale to assess
      perceived stress, the Perceived Stress Scale (PSS) by e-mail. RESULTS: The study
      showed that in women with a long-term history of endometriosis, the level of
      perceived stress was increased by repeated surgical treatments and reduced by
      some medical treatments. The median PSS value was 23 (range 9-36) and 30.6% of
      the study population were included in the highest stress category (>26). The
      highest levels were found in patients who had undergone the most surgery. The use
      of progestins was associated with a lower perceived stress (p = 0.004) than in
      the patients treated with gonadotropin-releasing hormones. CONCLUSIONS: Long-term
      endometriosis has a relevant impact on perceived stress, in particular in those
      undergoing repeated surgery.

PMID- 25591625
TI  - An astrocyte regenerative response from vimentin-containing cells in the spinal
      cord of amyotrophic lateral sclerosis's disease-like transgenic (G93A SOD1) mice.
AB  - The reason for regeneration in the adult spinal cord during motor neuron
      degeneration in amyotrophic lateral sclerosis (ALS) remains largely unknown. To
      this end, we studied the alteration of vimentin (a neural precursor cells marker
      in CNS)-containing cells (VCCs) in spinal cord during different stages of ALS
      used C57BL/6J G93A SOD1 transgenic mice mimicking ALS. Results showed that VCCs
      were mostly distributed in the ependymal zone (EZ) surrounding the central canal
      of spinal cord in SOD1 wild type mice; a few of VCCs were sparsely distributed in
      other regions. However, the number of VCCs significantly increased in the spinal
      cord during the onset and progression stages of ALS. They were extensively
      distributed in the EZ, the anterior, the lateral and the posterior horn of grey
      matter, particularly in the posterior horn region at the progression stage. A
      majority of VCCs in the anterior, the lateral and the posterior horn of grey
      matter (outside of EZ) generated astrocytes, but no neurons, oligodendrocytes and
      microgliocytes. Our results suggested that there was a potential astrocyte
      regenerative response to motor neuron degeneration in motor neurons-degenerated
      regions in the adult spinal cord during the onset and progression stages of ALS
      like disease. The regenerative responses in the adult spinal cord of ALS-like
      mice may be a potential pathway in attempting to repair the degenerated motor
      neurons and restore the dysfunctional neural circuitry.

PMID- 25591626
TI  - Secretor status and caries.

PMID- 25591629
TI  - [Stroke: the review of the problem (15 years after)].
AB  - The critical review of the key achievements in ischemic and hemorrhagic stroke of
      the past 15 years is presented in the article including stroke epidemiology and
      classification, experimental models, treatment of malignant edema after stroke,
      thrombolytic therapy, surgical treatment of intracranial hematomas, surgery on
      extracranial arteries, polyorganic insufficiency syndrome, secondary prevention
      of cardioembolic stroke, neuroprotection and early rehabilitation. 

PMID- 25591627
TI  - Cancer patient decision making related to clinical trial participation: an
      integrative review with implications for patients' relational autonomy.
AB  - PURPOSE: Oncology clinical trials are necessary for the improvement of patient
      care as they have the ability to confirm the efficacy and safety of novel cancer
      treatments and in so doing, contribute to a solid evidence base on which
      practitioners and patients can make informed treatment decisions. However, only 3
      5 % of adult cancer patients enroll in clinical trials. Lack of participation
      compromises the success of clinical trials and squanders an opportunity for
      improving patient outcomes. This literature review summarizes the factors and
      contexts that influence cancer patient decision making related to clinical trial
      participation. METHODS: An integrative review was undertaken within PubMed,
      CINAHL, and EMBASE databases for articles written between 1995 and 2012 and
      archived under relevant keywords. Articles selected were data-based, written in
      English, and limited to adult cancer patients. RESULTS: In the 51 articles
      reviewed, three main types of factors were identified that influence cancer
      patients' decision making about participation in clinical trials: personal,
      social, and system factors. Subthemes included patients' trust in their physician
      and the research process, undue influence within the patient-physician
      relationship, and systemic social inequalities. How these factors interact and
      influence patients' decision-making process and relational autonomy, however, is
      insufficiently understood. CONCLUSIONS: Future research is needed to further
      elucidate the sociopolitical barriers and facilitators of clinical trial
      participation and to enhance ethical practice within clinical trial enrolment.
      This research will inform targeted education and support interventions to foster
      patients' relational autonomy in the decision-making process and potentially
      improve clinical trial participation rates.

PMID- 25591630
TI  - [Psychotraumatic factors and anxiety-depressive spectrum disorders in Behcet's
      disease: the interdisciplinary study].
AB  - OBJECTIVE: To determine the frequency and variants of anxiety-depressive spectrum
      disorders (ADSD) in Behcet's disease (BD) and the effects of psychotraumatic
      factors, personality and clinical symptoms of the rheumatic disease. MATERIAL AND
      METHODS: Authors examined 60 patients with confirmed BD diagnosis made according
      to ISGBD criteria. The degree of BD activity was assessed using BDCAF index. The
      disease severity was ranged according to Ch. Zouboulis classification. All
      patients underwent complex rheumatologic, psychopathologic and psychological
      examinations. Childhood psychological trauma and stress factors before BD were
      analyzed. RESULTS: Most of the patients (86.7%) were diagnosed with a wide
      spectrum of ICD-10 ADSD: dysthymia (33.3%), recurrent depressive disorders
      (28.3%) mild or moderate depressive episode (11.7%), generalized anxiety disorder
      (6.7%), adjustment disorder with anxiety-depressive syndrome (6.7%). Mental
      disorders were not identified only in 13.3% of patients. The frequency of
      cognitive impairment (CI) was 88.3%, including 42.7% with mild CI. BD activity,
      ADSD severity and as well as factors not-related to disease contributed to CI
      development and severity. Psychological trauma during childhood and adolescence
      were found in 35 (58.3%) of patients. BD with early onset was recorded more often
      in the group with psychological trauma at the age <7 years compared to the group
      without psychological trauma. Treatment adherence was noted in most patients
      (70%) with BD and ADSD. CONCLUSION: The results confirm the need of timely
      diagnosis and adequate treatment of ADSD in patients with BD to improve treatment
      adherence and prognosis of disease.

PMID- 25591628
TI  - "Oh, yeah, I'm getting closer to god": spirituality and religiousness of family
      caregivers of cancer patients undergoing palliative care.
AB  - PURPOSE: Within the cancer palliative care setting, where both patients and
      family caregivers (FCs) undergo a transition from the end of curative treatment
      to palliative therapy, spirituality and religiousness (S/R) may be a strategy to
      help the patients and FCs better cope with the disease, in addition to exerting a
      positive impact on symptoms, particularly emotional symptoms. The present study
      aimed to understand how S/R influence FCs of cancer patients undergoing
      palliative care. METHODS: This study was an exploratory and descriptive
      qualitative study. The qualitative approach to the data was based on Bardin's
      content analysis technique. The consolidated criteria for reporting qualitative
      research (COREQ-32) was used in the description of the results. Thirty FCs of
      individuals with advanced cancer undergoing palliative care were included.
      RESULTS: Analysis of the FCs' narratives indicated that the FCs considered that
      religiousness and faith in God or a Supreme Being provide them with the strength
      to cope with the suffering associated with the care of relatives with advanced
      cancer. Many FCs emphasized that talking about God was somehow comforting and
      made them feel at peace with themselves. Four categories were identified in the
      FCs' narratives: (1) increase in faith and closeness to God becomes stronger, (2)
      rethink life issues, (3) negative interference in the extrinsic religiosity, and
      (4) quest for religiousness to gain strength or support. A conceptual framework
      was developed. CONCLUSIONS: The results of the present study indicated that S/R
      are a coping strategy frequently used by FCs of individuals with advanced cancer.
      The perceptions of the FCs interviewed in the present study corresponded to the
      four distinct categories related to spirituality and religiousness.

PMID- 25591631
TI  - [Clinical features of anxiety disorders in pregnant women].
AB  - OBJECTIVE: To study the frequency and clinical features of anxiety disorders
      during pregnancy. MATERIAL AND METHODS: One thousand women who were 8-40 weeks
      pregnant were examined. Anxiety disorders were noted in 98 cases, 90 of them were
      included in the study. A special form used in the study included medical and
      social/demographic data. Psychopathological examination and psychometric testing
      were performed. RESULTS AND CONCLUSION: Psychopathological heterogeneity of
      anxiety disorders was shown. The following syndromes were singled out: anxiety
      (20%), anxious-sub-depressive (10%), anxious-phobic (13.3%), anxious-depressive
      (10%) and a subsyndromal variant (37%).

PMID- 25591632
TI  - [The association between cerebral atrophy and amounts of alcohol consumption in
      alcoholic patients].
AB  - OBJECTIVE: To study the relationship between alcohol consumption and cerebral
      atrophic changes. MATERIAL AND METHODS: Forty-four second stage alcoholic
      patients at the age of 30-55 years were examined using magneto-resonance imaging
      of the brain combined with psychological testing of cognitive functions and the
      TLFB technique. Based on the TLFB technique, patients were stratified into mild
      and heavy alcohol consumers. RESULTS AND CONCLUSION: All patients had signs of
      atrophy in the cerebral cortex, especially in its fronto-parietal parts, the
      corpus callosum and paraventricular white matter. The degree of the atrophy and
      weakening of cognitive functions in the mild alcohol consumers was considerably
      higher than in the heavy alcohol consumers. This suggests the relatively higher
      sensitivity to alcohol in such patients that is associated with less favorable
      outcome.

PMID- 25591633
TI  - [Chronobiological characteristics of stroke and poststroke cognitive impairment].
AB  - OBJECTIVE: To study chronobiological characteristics of ischemic stroke (II) and
      post stroke cognitive impairment (CI). MATERIAL AND METHODS: We examined 80
      patients with acute ischemic stroke. The cognitive status, sleep quality,
      chronobiological parameters and night urinary level of 6-sulfatoxymelatonin were
      assessed. The clinical observation of the efficacy of melaxen treatment in
      intensive care unit was performed. RESULTS: The results of the study indicate the
      significance of social and environmental factors which determine the sleep-wake
      behavior in the development of pineal dysfunction. The pineal dysfunction
      probably underlies the development of stroke and accompanied neurodegenerative
      process. CONCLUSION: The use of melaxen in hyperacute stroke was associated with
      better recovery of circadian rhythms and rehabilitation results.

PMID- 25591634
TI  - [A role of carotid stenoses in the structure of early postoperative cognitive
      dysfunction in patients underwent coronary artery bypass grafting].
AB  - OBJECTIVE: To analyze the structure and severity of early postoperative cognitive
      dysfunction as well the accompanying spectral electroencephalographic (EEG)
      changes in patients underwent coronary artery bypass grafting (CABG) depending on
      the presence or absence of small and moderate internal carotid stenosis. MATERIAL
      AND METHODS: Fifty seven patients, aged from 45 to 70 years, were stratified into
      two groups: without stenosis (n=35, mean age 54.3+/-6.4 years) and with internal
      carotid stenosis (n=22, mean age of 57.5+/-5.8 years). For all patients planned
      on-pump CABG was performed. RESULTS: The frequency and severity of cognitive
      deficits in the postoperative period were higher in patients with internal
      carotid stenosis compared to patients without stenosis. Also, the patients with
      stenosis had more pronounced EEG signs of cortical dysfunction and brain damage
      after CABG compared to patients without stenosis. CONCLUSION: The presence of
      carotid >50% stenosis increases the severity of cognitive deficits and brain
      damage in patients underwent on-pump CABG.

PMID- 25591635
TI  - [Treatment of myofascial pain syndrome].
AB  - OBJECTIVE: To study different methods of treatment of patients with myofascial
      pain syndrome (MFPS). MATERIAL AND METHODS: We evaluated the efficacy of complex
      treatment in 152 patients with chronic tension-type headache (SEER) and 96
      patients with facial MFPS. The treatment included standard methods (reflex
      therapy of SEER and local injections of a combination of local anesthetics with
      small doses of steroids in trigger points in patients with facial MFPS. To assess
      the efficacy of tizanidine, patients were randomized into two comparable groups.
      The duration of the study was 12 weeks. RESULTS AND CONCLUSION: The combined
      therapy, including reflex action and tizanidine, speeds recovery from pain and
      ensures the stability of results.

PMID- 25591636
TI  - [Injectable extended-release naltrexone for opioid dependence: an open label
      study of long-term safety and efficacy].
AB  - OBJECTIVE: To evaluate efficacy and safety of injectable extended-release
      naltrexone (XR-NTX, Vivitrol), an opioid receptor antagonist, in the treatment of
      opioid dependence, we carried out a 1-year open-label extension study. MATERIAL
      AND METHODS: The study followed the initial 6-month randomized, double-blind, PBO
      controlled investigation of XR-NTX, used in dose 380 mg, as a treatment for
      opioid dependence. The study was conducted at 13 clinical sites in Russia. The
      main measurements were monthly urine samples (efficacy) and adverse events
      (safety). RESULTS AND CONCLUSION: The open-label extension included 114 patients
      (67 continued on XR-NTX and 47 switched from placebo). Overall, 62.3% (95% CI:
      52.7%, 71.2%) of patients completed the extension. Urine testing revealed that
      50.9% (41.5%, 60.4%) were abstinent from opioids at all assessments during the 1
      year open-label phase. Adverse events were reported by 21.1% of patients.
      Elevations in liver function tests occurred in 16.7% of patients. No severe
      adverse events were reported. The data obtained demonstrate the long-term safety
      and efficacy of XR-NTX in opioid dependent patients.

PMID- 25591637
TI  - [The use of tizanidine in combined treatment of arm poststroke spasticity].
AB  - OBJECTIVE: Muscle tone disorders, including poststroke spasticity, is a frequent
      cause of disability. We studied the efficacy and safety of tizalud (tizanidine)
      in patients with arm poststroke spasticity. MATERIAL AND METHODS: Forty-four
      patients were treated with tizalud and botulotoxin A in different doses in
      complex with rehabilitation measures or without them. RESULTS AND CONCLUSION: The
      marked improvement (the decrease in spasticity, increase in muscle power and pain
      syndrome intensity) was noted in patients treated with the combination of tizalud
      and botulotoxin A.

PMID- 25591638
TI  - [The use of neurometabolic treatment in the complex rehabilitation in poststroke
      patients].
AB  - OBJECTIVE: To analyze the effect of cytoflavin on neurological functions, the
      level of independence in daily living tasks, psychoemotional condition and
      quality of life in poststroke patients. MATERIAL AND METHODS: We have analyzed
      the results of treatment of 1450 stroke patients. Half of the patients received
      cytoflavin, and the other was treated without this drug. The functional
      rehabilitation was followed up using Barthel, Lindmark, Scandinavian and Merton
      and Sutton scales, psychoemotional condition was assessed with the Beck
      Depression Questionnaire and the Wakefield Depression Scale, quality of life -
      with the Sickness Impact Profile. RESULTS AND CONCLUSION: Cytoflavin improved the
      recovery of neurological functions and social adaptation, normalized the
      psychoemotional condition and increased quality of life of poststroke patients.

PMID- 25591639
TI  - [The Four-Dimensional Symptom Questionnaire (4DSQ) to assess distress,
      depression, anxiety and somatization in autonomic and borderline psychosomatic
      disorders].
AB  - OBJECTIVE: Autonomic nervous system disorders are a frequent reason that makes
      patients to seek medical advice from general physicians and neurologists in
      outpatient clinics. The Dutch Four-Dimensional Symptoms Questionnaire (4DSQ) used
      for measuring distress, depression, anxiety and somatization is an adequate tool
      for identifying psychogenic factors for the development of autonomic disorders.
      An aim of the study was to localize the questionnaire to the Russian population.
      MATERIAL AND METHODS: The questionnaire was translated and the Russian version
      was subsequently psychometrically validated. The statistical analysis conducted
      for the verification of compatibility of the Russian version with the Dutch
      version was based on the survey of 243 patients. RESULTS: All elements of the
      Russian version measured the same parameters of the Dutch 4DSQ. Some differences
      were identified. CONCLUSION: The analysis has confirmed the possibility of using
      the questionnaire in the Russian-speaking population using higher threshold
      values: +2 points for distress and anxiety, +4 points for somatization.

PMID- 25591640
TI  - [Biochemical markers of oxidative stress in different forms and phases of
      multiple sclerosis].
AB  - OBJECTIVE: To verify a role of oxidative stress in the pathogenesis of multiple
      sclerosis (MS) and to develop oxidative stress prognostic criteria of disease
      course and treatment recommendations. MATERIAL AND METHODS: We examined 220
      patients with different clinical forms and phases of MS. The lipid and protein
      free-radical oxidation markers were measured using the following parameters:
      ketodienes, diene conjugates, malondialdehyde, and Schiff bases. The functioning
      of the endogenous antioxidant defense system was assessed using y the activity of
      vitamin E, general and non-protein SH-groups, which represented the nonenzymatic
      segment of the antioxidant defense system. The enzymatic segment markers were
      superoxide dismutase, glutathione peroxidase, and glutathione reductase. RESULTS
      AND CONCLUSION: The findings revealed significant differences in the oxidative
      stress intensity indices in patients with different clinical forms and phases of
      MS, which made it possible to predict disease progression and prescribe the
      complex antioxidant treatment in the evidence-based practice.

PMID- 25591641
TI  - [Ultrastructural changes in platelets of schizophrenia patients: a link with
      serotonin metabolism and therapeutic efficacy].
AB  - OBJECTIVE: To investigate the effect of olanzapine treatment on the
      ultrastructure of granulated platelets (GP) and vacuolated platelets (VP) and to
      find their association with platelet serotonin (PS) content and treatment
      efficacy in patients with schizophrenia. MATERIALS AND METHODS: Platelets of 49
      patients with attack-like schizophrenia treated with olanzapine and 31 healthy
      people were explored. Electron microscopic morphometry of GP and VP was performed
      to estimate the ultrastructural parameters of platelets. Microfluorimetry was
      used to measure PS content. RESULTS; The number of pseudopodies in GP and VP were
      lower after 28 weeks with olanzapine (-13%, p<0.01) as compared to the patients
      before treatment but the mean platelet area was not changed. Vv of granules was
      reduced in VP after 8 and 28 weeks of olanzapine (-13%, p<0,05). Vv of vacuoles
      was increased in GP in 28 weeks with olanzapine vs. 8 weeks with olanzapine
      (+16%, p<0.01) and in VP in 28 weeks of treatment vs.patients before treatment
      (+13%, p<0.01). In patients before treatment, Vv of vacuoles in VP was
      significantly higher in nonresponders as compared to the responders (+11%,
      p<0.05) and significantly correlated with PS content (r=0.26, p=0.04). The
      association between the number and Vv of vacuoles in VP before treatment and time
      point for positive treatment effect was found for the first time. CONCLUSION:
      Ultrastructural changes in Vv of vacuoles in platelets of schizophrenia patients
      treated with olanzapine are associated with serotonin metabolism and therapeutic
      efficacy.

PMID- 25591642
TI  - [Problems and perspectives of teaching neurology to today's medical students].
AB  - Currently, the following statements in teaching neurology should be considered:
      1) the successful study of nervous diseases is impossible without knowledge of
      basic science (neuroanatomy, neurophysiology); 2) the feedback between the
      teacher and the student is important for effectiveness of teaching process; 3)
      theoretical knowledge should be combined with practical skills (communication
      between the young specialist and the patient, individual approach to the
      patient); 4) special attention should be drawn to the formation of personal
      qualities of the physician and ethical principles of future work. 

PMID- 25591643
TI  - [Features of the mental state of obese patients with concomitant sleep
      disorders].
AB  - OBJECTIVE: To study the frequency of mental disorders with concomitant insomnia
      in obese patients. MATERIAL AND METHODS: Authors studied 123 patients (51 men and
      72 women, mean age 40.0+/-11.5; body mass 117.6+/-30.9 kg; waist circumference
      118.2+/-19.8 cm; BMI 39.8+/-8.7 kg/m2) with obesity. RESULTS: The questionnaire
      survey revealed subjective disorders of the quality of sleep in 76%, complaints
      about snoring in 63%, hypersomnia during the day in 55% higher risk of sleep
      apnea in 50%, insomnia in 45% of patients. According to the results of
      psychological testing, the obese patients with insomnia had higher levels of
      health anxiety. CONCLUSION: Insomnia can be considered as a marker of overt
      psychopathological disturbances in patients with obesity.

PMID- 25591644
TI  - [A contemporary conception of insomnia syndrome and its treatments in view of
      International classification of sleep disorders].
AB  - Insomnia is one of the most common and wide-spread sleep disorders. It includes
      difficulties of sleep initiation, sustaining and daytime impairment. A condition
      of cerebral hyperarousal plays the most important role in the genesis of
      insomnia. Cognitive, electrophysiological and metabolic parameters are correlated
      with hyperarousal state. According to the International classification of sleep
      disorders (ICSD-3), insomnia is divided into acute, chronic and unclassified.
      Treatment of insomnia includes specific and nonspecific approaches. Regardless of
      the origin of insomnia, sleep hygiene and behavioral therapy remain the methods
      of choice for the treatment. 

PMID- 25591645
TI  - [Cerebrolysin in the treatment of brain injuries of moderate severity].
AB  - OBJECTIVE: To assess the efficacy of cerebrolysin in patients with cranial/brain
      injury of moderate severity. MATERIAL AND METHODS: The main group included 30
      patients treated with cerebrolysin from the first day of disease, the comparison
      group included 32 patients matched for age, sex and disease severity. RESULTS AND
      CONCLUSION: Cerebrolysin promoted the early and complete reduction of common
      symptoms of brain injury as well as autonomic and asthenic disorders, restoration
      of cognitive functions, normalization of emotional condition, improvement of
      spontaneous bioelectrical activity. The drug was well-tolerated.

PMID- 25591646
TI  - [A case of the cerebral vasculitis at the late stage of Kawasaki disease].
AB  - A description of the clinical observation of the child at the late stage of
      Kawasaki disease is presented. In our observation, an aneurysm of the circumflex
      branch of the left coronary artery was discovered on the echocardiography of the
      child. MRI results of the brain with vascular program revealed a picture of
      vasculitis, fusiform expansion of the A1 segment of the right anterior cerebral
      artery, M1 segment of the left middle cerebral artery. Systemic vasculitis was
      diagnosed at the late stage of disease. This case shows the importance of better
      awareness of pediatricians, cardiologists, neurologists about Kawasaki disease,
      its manifestations at the early stage and possible long-term complications, as
      well as modern approaches to treatment. 

PMID- 25591647
TI  - [Assessment of the efficacy and tolerability of melatonergic antidepressant
      treatment in patients surgical correction of the appearance].
AB  - Objective. To study the efficacy and tolerability of agomelatine (valdoxan) in
      the treatment of affective disorders developed after surgical correction of the
      appearance. Material and methods. We summarized 35 cases characterized by the
      development of ICD-10 depressive disorders after the face surgery performed to
      correct congenital and acquired malformations. Agomelatine was prescribed in dose
      25-50 mg daily during 6 weeks. Patient's state was assessed using
      psychopathological method and psychometric scales. Results and conclusion. We
      obtained significant results demonstrating the efficacy of this drug in mild and
      moderate depressive disorders. Agomelatine had a favorable tolerability profile
      that provided a high level of compliance of the patients. 

PMID- 25591648
TI  - [Cognitive impairment in depression and potential applications of antidepressants
      with procognitive effects].
AB  - The characteristics of cognitive impairment in depression are reviewed. Data of
      literature indicate that cognitive impairment may serve as a predictor of
      depression recurrence and poor prognosis of antidepressant therapy. In this view,
      we consider the importance of assessment of cognitive impairment and differential
      use of medications with precognitive effect (bupropion, vorteoxetine and some
      SSRI antidepressants as well as fluvoxamine, which is a potent agonist of the
      sigma-1-receptor). 

PMID- 25591649
TI  - [Rationale for the choice of medication based on the conception of the
      pathogenesis of mental disorder and mechanism of drug action].
AB  - In modern medicine, when prescribing drugs it is customary to take into account
      the pathogenesis of the disease and the mechanism of action of drugs. On the
      example of buspirone, authors have shown that in psychiatry recommendations for
      administration of drugs should also consider the pathogenesis of diseases
      (disorders) and the mechanism of drug action. These data will contribute to the
      rapprochement of neurology and psychiatry with other medical specialties. 

PMID- 25591650
TI  - [Indicators of treatment of schizophrenia in different stages of psychiatric
      care].
AB  - Objective. To study indicators of treatment of schizophrenia in different stages
      of psychiatric care, to reveal prognostic factors of the dynamics of
      psychopathological symptoms in treatment of schizophrenia and to estimate the
      risk of schizophrenia relapse. Material and methods. Three hundreds of patients,
      aged 18-65 years, diagnosed with schizophrenia (ICD-10) were included in data
      analysis. Patients were stratified into 4 groups by the type of psychiatric care:
      inpatients (n=68), outpatients of day hospital (n=71), outpatients of
      psychoneurological dispensary rehabilitation department (n=75) and outpatients
      supervised by psychoneurological dispensary local doctor. Treatment
      characteristics (use of 1st and 2nd generation antipsychotics) of these groups
      were compared. Results and conclusion. The positive effect of modern
      antipsychotics on schizophrenia course, frequency of relapses and
      hospitalizations was identified. The results can help in improvement of
      psychiatric care due to wide implementation of 2nd generation antipsychotics. 

PMID- 25591651
TI  - [The efficacy of add-on treatment with phenotropil in adult patients with locally
      induced epilepsy].
AB  - Objective. To study the efficacy and safety of phenotropil as add-on to treatment
      with standard antiepileptic drugs (AED) in patients with symptomatic locally
      induced epilepsy (SLIE). Material and methods. Double-blind placebo controlled
      randomized trial was carried out. Ninety patients were treated by phenotropil
      dose (100 or 200 mg) or placebo. MMSE, HAM-D, MFI-20 and encephalography,
      including R300 evoked potentials, were used. Results and conclusion. Phenotropil
      reduced the frequency of seizures and improved cognitive function in the absence
      of epileptiform EEG abnormalities. The drug did not decrease negative effects of
      standard AED therapy in 40% of patients. 

PMID- 25591652
TI  - [Antiepileptic drugs and seizure aggravation].
AB  - Objective. To analyze epileptic seizure aggravation associated with antiepileptic
      drugs (AED) in adult patients. Material and methods. We examined 1407 patients
      aged 18-89 years. Different patterns of seizure aggravation were identified in
      103 patients. Results. Aggravated seizures due the generic substitution were
      found in 32 patients. First was topiramate (TPM) (n=12), followed by valproates
      (VPA) (n=8), carbamazepine (CBZ) (n=5), lamotrigine (LTG) (n=1) and levetiracetam
      (LEV) (n=1). Patients with idiopathic generalized epilepsies (IGE) suffered
      aggravation with CBZ in 17 cases, VPA - in 6, TPM - in 6, LTG - in 1 and LEV - in
      1. CBZ aggravated absences in patients with juvenile absence epilepsy (JAE) were
      found in 5 cases of 17 (29.4%), with childhood absence epilepsy (CAE) - in 1 of
      24 (4.2%), absences and myoclonic jerks in juvenile myoclonic epilepsy (JME) - in
      9 of 47 (19.1%), absences with eyelid myoclonus (Jeavons syndrome) - in 2 of 11
      (18.2%). Seizure aggravations with different AEDs were observed in 13 patients.
      This pattern of aggravation was associated with resistant epilepsy and poor
      prognosis. Seizure aggravation due to increasing the dose of AEDs was found in 10
      cases and associated with resistant epilepsy and poor outcome. "True" aggravation
      was associated with CBZ in 34 patients, including 16 IGE patients, with TPM - in
      13, VPA - 5, LTG - 5, LEV - 2 and with clonazepam in 1 patient. Most often
      seizure aggravation was associated with CBZ in IGE patients (8.3%), and with LTG,
      TPM and CBZ in patients with other epileptic syndromes (non IGE): 4.9%, 4% and
      3.7%, respectively. Conclusions. Different AEDs can cause aggravation. Seizures
      aggravation after generic substitution was characteristic of TPM most frequently.
      Seizure aggravation with different AEDs and due to increasing the dose of AEDs
      was associated with poor outcome. In all cases, seizure aggravation was more
      frequently caused by LTG (4.7%), CBZ (3.7%) and TPM (3.3%). To reduce the risk of
      aggravation, slow AEDs titration and keeping a diary of seizures are required. 

PMID- 25591653
TI  - [The use of pregabalin without prescription].
AB  - Objective. Interest to pregabalin can be explained by the fact that the drug is
      purchased without prescription and used in nonmedical purposes. Authors performed
      the identification of pregabalin in the biological material (urine) of 16 364
      patients. Material and methods. Psychoactive substances were identified in a
      chemical-toxicological laboratory of a narcological dispensary in the Krasnodar
      region. Results and conclusion. Pregabalin was identified only in 0.1% of the
      patients. In all cases it was not used for the first time. Most often pregabalin
      was used to relieve abstinent syndrome in different types of addictions. The
      mechanisms of its action in these cases and potential danger of using without
      prescription are considered. 

PMID- 25591654
TI  - [A comparative study of mexidol and mexiprim pharmacokinetic parameters].
AB  - Objective. To compare pharmacokinetic parameters of mexidol (coated tablets,
      "Farmasoft") and mexiprim (tablets film-coated, "STADA CIS"). Material and
      methods. The study included 14 adult male Chinchilla rabbits. Concentration of 2
      ethyl-6-methyl-3-hydroxypyridine succinate in the blood plasma of animals was
      analyzed using HPLC with UV detection. Results and conclusion. Mexidol as
      compared to mexiprim was more completely and rapidly absorbed from the
      gastrointestinal tract, it was confirmed by the higher value of maximal
      concentration of 2-ethyl-6-methyl-3-hydroxypyridine succinate and less maximal
      concentration time after mexidol administration. The drugs had similar excretion
      that was confirmed by the lack of significant differences in the values of total
      clearance, half-life, and the average retention time. 

PMID- 25591655
TI  - [Towards the problem of disintegration and integration of medical disciplines on
      the example of a case report].
AB  - Authors present a case of a female patient with organic brain lesion, personality
      and behavioral disorder, pseudoepileptic seizures. Correct diagnosis and
      effective treatment became possible due to the mutual efforts of a neurologist
      and a psychiatrist. This example confirms the importance of clinical neurology
      and psychiatry integration. 

PMID- 25591656
TI  - [Recognition and awareness about stages of Alzheimer's disease].
AB  - Objective. To estimate the level of recognition of Alzheimer disease (AD) and
      awareness about its causes, medical help and its efficacy in general population.
      Material and methods. Authors questioned 1043 Chuvashia residents (391 men and
      652 women), aged from 18 to 81 years (mean age - 41.5+/-16.3 years ), using
      vignettes (a clinical "picture" of disease). A vignette describes the stages of
      AD (subclinical, mild, moderate and severe). Results. AD was determined correctly
      by 13.6% of respondents. Most difficulties were associated with definition of
      subclinical stage of disease (6.1% of correct answers). Good AD recognition
      depended on the level of education, including medical knowledge, age of
      respondents and previous experience with such cases. Visit to doctor was
      recommended by 83.1% (in most cases it was neurologist - 33%). The improvement of
      mental condition in illustrated cases was supposed by 60%, no improvement -
      28.9%, deterioration - 1.7%, without answer - 9.4% of respondents. Conclusion.
      These data indicates the low level of mental health literacy in the general
      population, especially on preclinical stage of AD. That needs to be corrected by
      psychiatric education at a general level. 

PMID- 25591658
TI  - Shedding light on the association between social support and adherence in
      hypertension: a comment on Magrin et Al.

PMID- 25591657
TI  - Expression of tumor necrosis factor receptor-assicated factor 4 correlates with
      expression of Girdin and promotes nuclear translocation of Girdin in breast
      cancer.
AB  - Overexpression of tumor necrosis factor receptor-associated factor 4 (TRAF4) has
      been reported in several human malignancies; however its association with Girdin
      in breast cancer is unclear. The aim of the present study was to analyze the
      correlation, expression and nuclear and cytoplasmic localizations of TRAF4 and
      Girdin in breast cancer tissues. Tissue samples from 38 patients with breast
      cancer, the MCF-10A normal mammary epithelial cell line, the MCF-7 estrogen
      receptor (ER)-positive and MDA-MB-231 ER-negative breast cancer cell lines were
      used in the present study. The results demonstrated that cytoplasmic expression
      of TRAF4 was positively correlated with cytoplasmic expression of Girdin.
      Furthermore, coexpression of TRAF4 and Girdin was highest in tissue samples from
      patients with lymph node metastases. Girdin was observed to be predominantly
      expressed in the cytoplasm of breast cancer cells; however TRAF4 promoted its
      translocation to the nucleus. These findings suggest that cytoplasmic expression
      of TRAF4 may be a novel potential marker for cell migration in breast cancer.

PMID- 25591659
TI  - Association norms for German noun compounds and their constituents.
AB  - We present a collection of association norms for 246 German depictable compound
      nouns and their constituents, comprising 58,652 association tokens distributed
      over 26,004 stimulus-associate pair types. Analyses of the data revealed that
      participants mainly provided noun associates, followed by adjective and verb
      associates. In corpus analyses, co-occurrence values for compounds and their
      associates were below those for nouns in general and their associates. The
      semantic relations between compound stimuli and their associates were more often
      co-hyponymy and hypernymy and less often hyponymy than for associations to nouns
      in general. Finally, we found a moderate correlation between the overlap of the
      associations to compounds and their constituents and the degree of semantic
      transparency. These data represent a collection of associations to German
      compound nouns and their constituents that constitute a valuable resource
      concerning the lexical semantic properties of the compound stimuli and the
      semantic relations between the stimuli and their associates. More specifically,
      the norms can be used for stimulus selection, hypothesis testing, and further
      research on morphologically complex words. The norms are available in text format
      (utf-8 encoding) as supplemental materials. 

PMID- 25591660
TI  - Binge Drinking among Men Who Have Sex with Men and Transgender Women in San
      Salvador: Correlates and Sexual Health Implications.
AB  - High rates of heavy alcohol use among men who have sex with men (MSM) and
      transgender women (TW) have been linked to increased vulnerability for HIV and
      poor mental health. While theories explaining elevated drinking levels among
      sexual minorities have been forwarded, few investigations have assessed the
      potential pathways using empirical data, particularly with an explicit focus on
      self-stigma and among MSM and TW in low- and middle-income countries. This study
      examined the relationship between stigma-related stress (specifically, self
      stigma and concealment of one's sexual orientation) and binge drinking in a
      sample of MSM and TW (n = 670) in San Salvador, El Salvador, recruited using
      respondent-driven sampling. Levels of alcohol consumption among participants were
      high: only 39 % of the sample did not drink alcohol or did not binge drink, while
      34 % engaged in binge drinking at least weekly. Among MSM, high self-stigma was
      associated with binge drinking at least weekly (adjusted relative risk ratio
      (aRRR) = 2.1, p < 0.05). No such relationship was found with less than weekly
      binge drinking. Among both MSM and TW, having a female partner was associated
      with binge drinking less than weekly (aRRR = 3.3, p < 0.05) and binge drinking at
      least weekly (aRRR = 3.4, p < 0.05), while disclosure of sexual orientation to
      multiple types of people was associated with binge drinking less than weekly
      (aRRR = 2.9 for disclosure to one-two types of people, p < 0.01; aRRR = 4.0 for
      disclosure to three-nine types of people, p < 0.01). No such relationship was
      found with at least weekly binge drinking. Binge drinking at least weekly was
      marginally associated with a number of sexual health outcomes, including high
      number of lifetime partners (adjusted odds ratio (aOR) = 1.7, p < 0.10),
      inconsistent condom use with a non-regular partner (aOR = 0.5, p < 0.10), and
      decreased intention to test for HIV in the next 12 months (aOR = 0.6, p < 0.10).
      With the exception of inconsistent condom use with a non-regular partner (aOR =
      0.4, p < 0.05), binge drinking less than weekly was not associated with increased
      sexual risk behavior and was actually associated with increased intention to test
      for HIV in the next 12 months (aOR = 2.8, p < 0.01). These findings support
      multiple pathways linking stigma-related stress to alcohol use. Specifically,
      those with high self-stigma and identity concealment may be using alcohol as a
      maladaptive coping and emotion regulation strategy, while those who have
      disclosed their sexual orientation to multiple types of people may be more
      engaged with the sexual minority community, likely in bars and other venues where
      permissive norms for alcohol use prevail. That this frequency of binge drinking
      does not appear to be associated with increased sexual risk behavior (and may
      even be associated with increased intention to test for HIV in the next 12
      months) lends further support to the suggestion that these individuals with
      healthy concepts of the self (as indicated by high levels of disclosure and low
      levels of risky sexual behavior) may engage in binge drinking because of the
      influence of the social environment. Further research is needed to establish the
      pathways linking stigma-related stress to heavy alcohol use so that points of
      intervention can be identified. 

PMID- 25591661
TI  - Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in
      case-control sample sets.
AB  - A genome-wide association study of gout in European populations identified 12
      genetic variants strongly associated with risk of gout, but it is unknown whether
      these variants are also associated with gout risk in Chinese populations. A total
      of 145 patients with gout and 310 healthy control patients were recruited for a
      case-control association study. Twelve SNPs of CLNK and ZNF518B gene were
      genotyped, and association analysis was performed. Odds ratios (ORs) with 95 %
      confidence intervals (CIs) were used to assess the association. Overall, we found
      four risk alleles for gout in patients: the allele "G" of rs2041215 and rs1686947
      in the CLNK gene by dominant model (OR 1.66; 95 % CI 1.04-2.63; p = 0.031) (OR
      2.19; 95 % CI 1.38-3.46; p = 0.001) and additive model (OR 1.39; 95 % CI 1.00
      1.93; p = 0.049) (OR 1.67; 95 % CI 1.19-2.32; p = 0.003), respectively, and the
      allele "A" of rs10938799 and rs10016022 in ZNF518B gene by recessive model (OR
      4.66; 95 % CI 1.44-15.09; p = 0.008) (OR 4.54; 95 % CI 1.23-16.76; p = 0.020).
      Further haplotype analysis showed that the TCATTCTGA haplotype of CLNK was more
      frequent among patients with gout (adjusted OR 0.48; 95 % CI 0.24-0.95; p =
      0.036). Additionally, polymorphisms of rs2041215, rs10938799, and rs17467273 were
      also correlated with clinical pathological parameters. This study provides
      evidence for gout susceptibility genes, CLNK and ZNF518B, in a Chinese
      population, which may have potential as diagnostic and prognostic marker for gout
      patients. 

PMID- 25591662
TI  - SubPatCNV: approximate subspace pattern mining for mapping copy-number
      variations.
AB  - BACKGROUND: Many DNA copy-number variations (CNVs) are known to lead to
      phenotypic variations and pathogenesis. While CNVs are often only common in a
      small number of samples in the studied population or patient cohort, previous
      work has not focused on customized identification of CNV regions that only
      exhibit in subsets of samples with advanced data mining techniques to reliably
      answer questions such as "Which are all the chromosomal fragments showing nearly
      identical deletions or insertions in more than 30% of the individuals?". RESULTS:
      We introduce a tool for mining CNV subspace patterns, namely SubPatCNV, which is
      capable of identifying all aberrant CNV regions specific to arbitrary sample
      subsets larger than a support threshold. By design, SubPatCNV is the
      implementation of a variation of approximate association pattern mining algorithm
      under a spatial constraint on the positional CNV probe features. In benchmark
      test, SubPatCNV was applied to identify population specific germline CNVs from
      four populations of HapMap samples. In experiments on the TCGA ovarian cancer
      dataset, SubPatCNV discovered many large aberrant CNV events in patient
      subgroups, and reported regions enriched with cancer relevant genes. In both
      HapMap data and TCGA data, it was observed that SubPatCNV employs approximate
      pattern mining to more effectively identify CNV subspace patterns that are
      consistent within a subgroup from high-density array data. CONCLUSIONS: SubPatCNV
      available through http://sourceforge.net/projects/subpatcnv/ is a unique scalable
      open-source software tool that provides the flexibility of identifying CNV
      regions specific to sample subgroups of different sizes from high-density CNV
      array data.

PMID- 25591664
TI  - Situational awareness and information flow in prehospital emergency medical care
      from the perspective of paramedic field supervisors: a scenario-based study.
AB  - BACKGROUND: In prehospital emergency medical services, one of the key factors in
      the successful delivery of appropriate care is the efficient management and
      supervision of the area's emergency medical services units. Paramedic field
      supervisors have an important role in this task. One of the key factors in the
      daily work of paramedic field supervisors is ensuring that they have enough of
      the right type of information when co-operating with other authorities and making
      decisions. However, a gap in information sharing still exists especially due to
      information overload. The aim of this study was to find out what type of critical
      information paramedic field supervisors need during multi-authority missions in
      order to manage their emergency medical services area successfully. The study
      also investigated both the flow of information, and interactions with the
      paramedic field supervisors and the differences that occur depending on the
      incident type. METHODS: Ten paramedic field supervisors from four Finnish rescue
      departments participated in the study in January-March 2012. The data were
      collected using semi-structured interviews based on three progressive real-life
      scenarios and a questionnaire. Data were analysed using deductive content
      analysis. Data management and analysis were performed using Atlas.ti 7 software.
      RESULTS: Five critical information categories were formulated: Incident data,
      Mission status, Area status, Safety at work, and Tactics. Each category's
      importance varied depending on the incident and on whether it was about
      information needed or information delivered by the paramedic field supervisors.
      The main communication equipment used to receive information was the authority
      radio network (TETRA). However, when delivering information, mobile phones and
      TETRA were of equal importance. Paramedic field supervisors needed more
      information relating to area status. CONCLUSIONS: Paramedic field supervisors
      communicate actively with EMS units and other authorities such as Emergency
      Medical Dispatch, police, and rescue services during the multi-authority
      incidents. This study provides knowledge about the critical information
      categories when receiving and sharing the information to obtain and maintain
      situational awareness. However, further research is needed to examine more the
      information flow in prehospital emergency care to enable a better understanding
      of required communication in situational awareness formation.

PMID- 25591663
TI  - Inhibitory effect of zingiber officinale towards Streptococcus mutans virulence
      and caries development: in vitro and in vivo studies.
AB  - BACKGROUND: Streptococcus mutans is known as a key causative agent of dental
      caries. It metabolizes dietary carbohydrate to produce acids which reduce the
      environmental pH leading to tooth demineralization. The ability of this bacterium
      to tolerate acids coupled with acid production, allows its effective colonization
      in the oral cavity leading to the establishment of highly cariogenic plaque. For
      this reason, S. mutans is the only bacterium found in significantly higher
      numbers than other bacteria in the dental plaque. The aim of this study was to
      evaluate the effect of crude extract and methanolic fraction of Z. officinale
      against S. mutans virulence properties. RESULTS: We investigated in vitro and in
      vivo activity of crude extract and methanolic fraction at sub- MIC levels against
      cariogenic properties of S. mutans. We found that these extracts strongly
      inhibited a variety of virulence properties which are critical for its
      pathogenesis. The biofilm formation in S. mutans was found to be reduced during
      critical growth phases. Furthermore, the glucan synthesis and adherence was also
      found to be inhibited. Nevertheless, the insoluble glucan synthesis and sucrose
      dependent adherence were apparently more reduced as compared to soluble glucan
      synthesis and sucrose- independent adherence. Biofilm architecture inspected with
      the help of confocal and scanning electron microscopy, showed dispersion of cells
      in the treated group as compared to the control. The Quantitative Real Time PCR
      (qRT-PCR) data had shown the down regulation of the virulence genes, which is
      believed to be one of the major reasons responsible for the observed reduction in
      the virulence properties. The incredible reduction of caries development was
      found in treated group of rats as compared to the untreated group which further
      validate our in vitro data. CONCLUSION: The whole study concludes a prospective
      role of crude extract and methanolic fraction of Z. officinale in targeting
      complete array of cariogenic properties of S. mutans, thus reducing its
      pathogenesis. Hence, it may be strongly proposed as a putative anti- cariogenic
      agent.

PMID- 25591665
TI  - Demonstration of a low-frequency three-dimensional terahertz bullet with extreme
      brightness.
AB  - The brightness of a light source defines its applicability to nonlinear phenomena
      in science. Bright low-frequency terahertz (<5 THz) radiation confined to a
      diffraction-limited spot size is a present hurdle because of the broad bandwidth
      and long wavelengths associated with terahertz (THz) pulses and because of the
      lack of THz wavefront correctors. Here using a present-technology system, we
      employ a wavefront manipulation concept with focusing optimization leading to
      spatio-temporal confinement of THz energy at its physical limits to the least
      possible three-dimensional light bullet volume of wavelength-cubic. Our scheme
      relies on finding the optimum settings of pump wavefront curvature and post
      generation beam divergence. This leads to a regime of extremely bright PW m(-2)
      level THz radiation with peak fields up to 8.3 GV m(-1) and 27.7 T surpassing by
      far any other system. The presented results are foreseen to have a great impact
      on nonlinear THz applications in different science disciplines. 

PMID- 25591666
TI  - Essential roles of leucine-rich glioma inactivated 1 in the development of
      embryonic and postnatal cerebellum.
AB  - Leucine-rich glioma inactivated 1 (LGI1) is a secreted protein that interacts
      with ADAM transmembrane proteins, and its mutations are linked to human epilepsy.
      The function of LGI1 in CNS development remains undefined. Here, we report novel
      functions of LGI1 in the generation of cerebellar granule precursors (CGPs) and
      differentiation of radial glial cells (RGCs) in the cerebellum. A reduction in
      external granule layer thickness and defects in foliation were seen in embryonic
      and new-born LGI1 knockout (KO) mice. BrdU staining showed an inhibited
      proliferation of CGPs in KO embryos, which might be explained by the reduced
      Sonic hedgehog in embryos. In addition, the differentiation of RGCs into Bergmann
      glias was suppressed in KO mice. Enhanced Jagged1-Notch1 signaling in KO mice via
      reduced beta-secretase proteolysis suggests that altered phenotype of RGCs is due
      to abnormal Notch1 signaling. Together, our results demonstrate that LGI1 is an
      essential player in the cerebellar development. 

PMID- 25591667
TI  - An association between milk and slime increases biofilm production by bovine
      Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus is associated with chronic mastitis in cattle,
      and disease manifestation is usually refractory to antibiotic therapy. Biofilm
      production is a key element of S. aureus pathogenesis and may contribute to the
      treatment failure that is consistently reported by veterinarians. Minas Gerais
      State is the largest milk-producing state in Brazil, and the characterization of
      bacterial isolates is an important aspect of disease control for dairy farmers.
      Here, we investigated the potential of S. aureus isolated from bovine mastitis to
      produce slime and biofilm in a skim-milk medium and classified the isolates
      according to their agr type. RESULTS: Slime was detected using the Congo Red agar
      (CRA) test in 35.18% (19/54) of the strains; however, 87.04% (47/54) of the
      strains were considered biofilm-positive based on crystal violet staining.
      Compared to TSB supplemented with 0.25% glucose, skim milk significantly
      increased the production of biofilm, but this effect was only observed in slime
      producing strains. The bacteria belonged to agr groups I (12/54), II (34/54), III
      (6/54), and IV (2/54), and bacteria in agr group III were found to be stronger
      biofilm producers than those in groups I and II. Again, milk had a significant
      influence only on slime-positive agr I and II isolates, revealing an association
      between milk and slime. CONCLUSIONS: The present study demonstrated that skim
      milk medium and slime production are two factors that together influence biofilm
      formation by bovine strains of S. aureus. A predominance of bacteria belonging to
      agr group II was observed, and bacteria from agr group III showed the highest
      proportion of biofilm producers. The majority of bacteria characterized in this
      study formed biofilm in milk, which suggests that biofilm formation has an
      important role in the virulence of S. aureus isolated from bovine intramammary
      infections.

PMID- 25591668
TI  - Head injury due to vehicular accidents.

PMID- 25591669
TI  - Epidemiology of neurological disorders in India: review of background, prevalence
      and incidence of epilepsy, stroke, Parkinson's disease and tremors.
AB  - Growth and development of neuroepidemiology in India during the last four decades
      has been documented highlighting the historical milestones. The prevalence rates
      of the spectrum of neurological disorders from different regions of the country
      ranged from 967-4,070 with a mean of 2394 per 100,000 population, providing a
      rough estimate of over 30 million people with neurological disorders (excluding
      neuroinfections and traumatic injuries). Prevalence and incidence rates of common
      disorders including epilepsy, stroke, Parkinson's disease and tremors determined
      through population-based surveys show considerable variation across different
      regions of the country. The need for a standardized screening questionnaire,
      uniform methodology for case ascertainment and diagnosis is an essential requiste
      for generating robust national data on neurological disorders. Higher rates of
      prevalence of neurological disorders in rural areas, 6-8 million people with
      epilepsy and high case fatality rates of stroke (27-42%) call for urgent
      strategies to establish outreach neurology services to cater to remote and rural
      areas, develop National Epilepsy Control Program and establish stroke units at
      different levels of health care pyramid.

PMID- 25591670
TI  - Approach to diagnosis and management of optic neuropathy.
AB  - Visual loss consequent to anterior visual pathway involvement can occur in a
      variety of clinical settings. In a tropical country like India, apart from the
      usual suspects, nutritional, infective, and toxic amblyopia have to be considered
      in the differential diagnosis. The mode of onset (acute/chronic), unilateral
      versus bilateral involvement, accompanying occular pain or the lack of it, and
      pattern of visual loss are some of the pointers which help to differentiate optic
      neuropathy clinically. The presence of concurrent neurological deficits, evidence
      of other systemic illnesses, and the results of serological and radiological
      investigations help to confirm the diagnosis. This article briefly describes the
      important causes of optic neuropathy in the Indian context and outlines a
      practical approach to management. 

PMID- 25591671
TI  - Epilepsy: some controversies, some knowledge and some experience from Cambodia.
AB  - Epilepsy-related health outcomes remain unacceptably low in much of the
      developing world. According to us, it is because of the failure since long to
      see, and address, epilepsy beyond its preset conventional image. The objective of
      this paper was to highlight the presence, and influence, of these conventional
      practices and also to demonstrate what happened when a bold unconventional
      approach to address epilepsy was taken in Cambodia. Data are taken from existing
      published literature on epilepsy as well as our field experience during several
      population-based surveys conducted in Cambodia. We complimented this with our
      knowledge gained over this long period. It is demonstrated that epilepsy is far
      more important in Asia that it is currently considered to be, and also vis-a-vis
      other geographic regions. Pregnancy and birth-related factors carry far higher
      odds for epilepsy than several "highly vocal" infections. A refocus in epilepsy
      is required to help move from its traditional negative image to an image where
      epilepsy is considered a "positive-looking" disorder that is full of
      "opportunities;" such as availability of safe effective inexpensive treatment,
      etc. Stigma is a two-side entity (i.e., it is present, and it is influential),
      and diligence should be therefore practiced before using the stigma label.
      Nevertheless, psychosocial aspects shouldn't be limited to stigma or Jacoby
      stigma scale alone. Quality of life is a subjective phenomenon, and patients
      should determine directly what affects them. It is highly desirable that if we
      want to find newer answers to old problems in epilepsy, we need to shed our
      conventional approach and preset conclusions. We should choose to move toward
      "opportunities" visibly present in epilepsy. Our Cambodian experience
      demonstrates more intimately that opportunities do get identified when preset
      conclusions are questioned, and an approach that goes beyond expected and by
      default is taken.

PMID- 25591672
TI  - Profile of patients with head injury among vehicular accidents: an experience
      from a tertiary care centre of India.
AB  - BACKGROUND: Pattern of injuries among drivers, pillion riders and co-passengers
      of two and four-wheeler vehicles need to be separately evaluated and addressed.
      MATERIALS AND METHODS: A prospective study was conducted on 1545 patients (1314
      males and 231 females) between 01 April, 2011 to 31 December, 2011, to evaluate
      the profile of head injury patients due to road traffic accidents, admitted in
      Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh.
      Proper subset of cases and controls with or without helmet, seat belt and history
      of alcohol intake were compared. Data was analyzed to evaluate the incidence,
      severity, pattern of head injury and outcome of the patients. RESULTS: Male
      drivers of two-wheeler vehicular accidents (71.4%) were most commonly injured.
      Among helmeted patients, only 4.8% sustained severe head injuries compared to
      23.7% of un-helmeted patients. Only full coverage helmets were effective in
      preventing head injury. Among helmeted patients with a proper chinstrap, 2.6%
      suffered critical injuries compared to 14% of non-strapped ones. In 142 patients,
      helmet was at position after the crash and only 0.7% of these sustained severe
      head injuries. Drunk driving was noticed among 19% and 6% of two- and four
      wheeler vehicular occupants, respectively. Only 7.5% of the four-wheel vehicular
      occupants were wearing seat belt at the time of accident. CONCLUSIONS: Injury
      profile of two- and four-wheeler vehicular accident victims is entirely
      different. A ready supply of affordable helmets of appropriate quality and strict
      legislation for safety constraints is the need of the hour for road safety.

PMID- 25591673
TI  - First Indian single center experience with pipeline embolization device for
      complex intracranial aneurysms.
AB  - BACKGROUND: Flow diversion is a novel method of therapy wherein an endoluminal
      sleeve, the flow diverter stent is placed across the neck of complex aneurysms to
      curatively reconstruct abnormal vasculature. We present the first Indian single
      center experience with the pipeline embolization device (PED) and 6 months follow
      up results of 5 patients. SUBJECTS AND METHODS: Five complex or recurrent
      intracranial aneurysms in five patients were treated with PED. The patients were
      followed-up with magnetic resonance angiography (MRA) after 4 weeks and
      conventional angiography after 6 months. Feasibility, complications, clinical
      outcome, early 1-month MRA and 6 months conventional angiographic follow-up
      results were analyzed. RESULTS: Of the five aneurysms treated, four were in the
      anterior circulation and one in the posterior circulation. All five patients were
      treated with a single PED in each, and additionally coils were used in one
      patient. At 1-month MRA follow-up, complete occlusion was seen in 2 (40%) of the
      five cases. Post 6 months conventional angiography showed complete occlusion of
      the aneurysm sac in all five cases (100%). Side branch ostia were covered in
      three patients, all of which were patent (100%). There was no incidence of major
      neurological morbidity or mortality. One patient (20%) who had basilar top
      aneurysm experienced minor neurological disability after 5 days which partially
      improved. CONCLUSIONS: Pipeline embolization device for complex and recurrent
      aneurysms is technically feasible, safe, offers low complication rate, and
      definitive vascular reconstruction. PED can be used without fear of occlusion of
      covered eloquent side branches and perforators.

PMID- 25591674
TI  - Assessment of risk factors for earlier onset of sporadic Alzheimer's disease
      dementia.
AB  - BACKGROUND: Pharmacological treatment has mild effects for patients with
      Alzheimer's disease dementia (AD); therefore, the search for modifiable risk
      factors is an important challenge. Though risk factors for AD are widely
      recognized, elements that influence the time of dementia onset have not been
      comprehensively reported. We aimed to investigate which risk factors might be
      related to the age of onset of AD in a sample of patients with highly variable
      educational levels, taking into account the Framingham risk scoring as the sole
      measure of vascular risk. SUBJECTS AND METHODS: We included 209 consecutive late
      onset AD patients to find out which factors among educational levels, coronary
      heart disease risk estimated by way of Framingham risk scores, history of head
      trauma or depression, surgical procedures under general anesthesia, family
      history of neurodegenerative diseases, gender, marital status and APOE haplotypes
      might be related to the age of dementia onset in this sample of patients with low
      mean schooling. RESULTS: Mean age of AD onset was 73.38+/-6.5 years old,
      unaffected by schooling or family history of neurodegenerative diseases. Patients
      who were APOE-epsilon4 carriers, married, or with history of depression, had
      earlier onset of AD, particularly when they were women. Coronary heart disease
      risk was marginally significant for later onset of AD. CONCLUSIONS: APOE
      haplotypes, marital status and history of depression were the most important
      factors to influence the age of AD onset in this sample. While midlife
      cerebrovascular risk factors may increase incidence of AD, they may lead to later
      dementia onset when present in late life.

PMID- 25591675
TI  - Combination therapy of intravenous glycoprotein IIB/IIIA inhibitors and tissue
      plasminogen activator for acute ischemic stroke.
AB  - OBJECTIVES: Retrospective pooled analysis of data from published prospective
      studies and randomized phase 1 and 2 trials was done to assess efficacy and
      safety profile of intravenous combination therapy [glycoprotein IIb/IIIa
      inhibitors and IV tissue plasminogen activator (tPA)] in management of acute
      ischemic stroke. MATERIALS AND METHODS: We searched Cochrane Central Register of
      Controlled Trials, MEDLINE, PubMed, and EMBASE databases; two reviewers
      independently selected studies reporting safety endpoints and outcome measures in
      acute ischemic stroke patients treated with combination therapy. tPA arm of the
      National Institute of Neurological Disorders and Stroke (NINDS) tPA trial was
      included in tPA-only group. Weighted means and proportions were calculated for
      numeric and categorical variables respectively. Bivariate analysis using Fisher's
      exact test was done to compare baseline descriptors, safety endpoints, and
      outcome measures. RESULTS: Combination therapy arm included 188 patients and IV
      tPA arm had 218 patients. Mean National Institutes of Health Stroke Scale (NIHSS)
      in two groups were 12.8 and 14.6, respectively. Mean time-to-treatment was 2.3
      hours in combination therapy arm and 2.55 hours in tPA arm. Treatment with
      combination therapy was associated with significant reduction in rate of
      symptomatic intracranial hemorrhage (sICH) [odds ratio (OR) 0.26, 95% cumulative
      incidence (CI) 0.07 0.83, P value 0.01). Difference in better functional outcome
      at 90 days (OR 0.87, 95% CI 0.59-1.30, P value 0.54) and death at 90 days (OR
      1.16, 95% CI 0.69-1.93, P value 0.60) were not significantly different in two
      groups. CONCLUSION: Combination of low dose IV TPA with glycoprotein IIb/IIIa
      inhibitors is associated with reduction in sICH rates in patients with acute
      ischemic stroke as compared to standard dose of IV tPA.

PMID- 25591676
TI  - Clinical heterogeneity and a high proportion of novel mutations in a Chinese
      cohort of patients with dysferlinopathy.
AB  - BACKGROUND AND AIMS: Dysferlinopathies are a group of autosomal recessive
      muscular dystrophies caused by mutations in the dysferlin gene. This study
      presents clinical features and the mutational spectrum in the largest cohort of
      Chinese patients analyzed to date. PATIENTS AND METHODS: A total of 36 unrelated
      Chinese patients with diagnostic suspicion of dysferlinopathy were clinically and
      genetically characterized. RESULTS: Patients were divided into five phenotypes:
      19 patients with limb girdle muscular dystrophy (LGMD) type 2B, 10 with Miyoshi
      myopathy (MM), 1 with distal anterior compartment myopathy (DACM), 3 with
      exercise intolerance, and 3 with asymptomatic hypercreatine phosphokinasemia
      (hyperCPKemia). Thirty-one patients showed an absence or drastic reduction of
      dysferlin expression by Westernblot. Forty-three mutations were identified in
      DYSF, including 31 novel. CONCLUSION: Our study underlines clinical heterogeneity
      and a high proportion of novel mutations in Chinese patients affected with
      dysferlinopathy.

PMID- 25591677
TI  - Endoscopic decompression of cervical spondylotic myelopathy using posterior
      approach.
AB  - BACKGROUND: Cervical spondylotic myelopathy, radiculopathy and myeloradiculopathy
      can be managed by laminoforaminotomy, or bilateral decompression using posterior
      approach in single or multilevel compression. Posterior endoscopic techniques
      allow preservation of motion segment and neural decompression without fusion.
      MATERIALS AND METHODS: A prospective study of 50 patients of cervical compressive
      myelopathy with primarily posterior lesion or multilevel anterior compression
      with acceptable preoperative lordosis was undertaken. Any instability,
      significant anterior compression, and cervical myelopathy secondary to tumor,
      trauma, severe ossification of posterior longitudinal ligament, rheumatoid
      arthritis, pyogenic spondylitis, and destructive spondylo-arthropathy were
      excluded from the study. There were 5, 23, 12, 10 patients with 2, 3, 4, 5
      vertebral body level pathologies, respectively. RESULTS: There were 2, 4, 7, 32,
      and 5 patients in preoperative Nurick grade 0, 1, 2, 3, and 4, respectively with
      an average of 2.6 grades. All the patients improved in post-operative grading
      with 10, 34, and 6 patients in 0, 1, and 2 grades (average 0.92), respectively.
      Better outcome was observed in patients with good preoperative grade and in short
      segment compression on cord. There was no change in cervical Cobb angle after
      surgery. Follow-up ranged from 6 to 24 months (averages 19 months). There was
      small dural tear, minor bleeding from muscles or epidural vessels and temporary C
      5 root injury in 1, 3, and 2 patients, respectively. CONCLUSION: Endoscopic
      decompression of cervical spondylotic myelopathy is a safe and an effective
      alternative treatment option in selected patients when pathologic changes are
      primarily posterior or multi level anterior lesions with acceptable preoperative
      lordosis.

PMID- 25591678
TI  - Mycophenolate mofetil in the treatment of multiple sclerosis: a preliminary
      report.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is an affordable and tolerable drug
      reported to be beneficial in the treatment of multiple sclerosis (MS). AIM: To
      determine efficacy of MMF as first line disease modifying drug (DMD) in 40
      patients with MS seen in our demyelinating disease registry. MATERIALS AND
      METHODS: The annualized relapse rate (ARR) for 1 year prior to starting MMF
      therapy and 1 year post treatment was calculated. Pre- and post-treatment
      expanded disability status scores (EDSS), age at onset of treatment, disease
      duration, and type of MS were recorded. Wilcoxon rank sum test was used for
      comparison of ARRs and EDSS before and after treatment. RESULTS: Forty patients
      included 27 females and 13 males. Mean duration of MMF therapy was 24 months
      (range 14-33 months). Pre-treatment mean ARR of 0.95 was significantly different
      from post treatment mean ARR of 0.11 (P=0.0001). Pre-treatment mean EDSS 3.80
      (inter quartile range [IQR] 3.5-4.5) was significantly different from post
      treatment mean EDSS 2.66 (IQR 1.5-3.0, P=0.0001). No adverse effects were
      reported that required stopping of medication. Five patients discontinued
      treatment 6-11 months after starting therapy, two of whom relapsed subsequently.
      CONCLUSION: Our preliminary results support the use of MMF, a cheap and well
      tolerated drug, as first line disease modifying drug in MS. Long-term results in
      a larger patient cohort is required for validating our preliminary conclusions.

PMID- 25591679
TI  - Co-morbidity of depression and epilepsy in Jimma University specialized hospital,
      Southwest Ethiopia.
AB  - BACKGROUND: Depression is a serious and frequent co-morbid illness among people
      with epilepsy (PWE) and the risk for depression in PWE is higher than the general
      population. However, depression among PWE is often under diagnosed and treated by
      physicians other than psychiatrists in resource-limited settings like Ethiopia.
      OBJECTIVE: This study aimed at assessing the prevalence and factors associated
      with depression and its implication for treatment among PWE in Southwest
      Ethiopia. MATERIALS AND METHODS: A hospital-based cross-sectional study design
      was facilitated among 300 adult subjects diagnosed with epilepsy at the Jimma
      University Specialized Hospital (JUSH) from August to October 2012. Depression
      was assessed using the Beck Depression Inventory-II (BDI-II) scale which was
      found to have Cronbach's Alpha of 0.82 for this study. RESULTS: A total of 300
      adult subjects with epilepsy were interviewed making a response rate of 100%. The
      prevalence of depressive disorder among patient with epilepsy was 49.3%. Of
      these, 39.9%, 38.5%, and 21.6% of the patient were found to have mild, moderate,
      and severe depression, respectively. Epilepsy-related perceived stigma, high
      seizure frequency, and low educational status were found to be independent
      predictors of depression among subjects with epilepsy. CONCLUSION: In this study,
      depression was found to be highly prevalent. Early recognition and treatment of
      depression through routine screening and assessment of PWE should become an
      essential part of diagnosis and treatment protocol.

PMID- 25591680
TI  - Prevalence of neuropathy in patients with impaired glucose tolerance using
      various electrophysiological tests.
AB  - BACKGROUND: Neuropathy is often an associated feature woth long-standing type II
      diabetes mellitus. Neuropathy may occur even in subjects with impaired glucose
      tolerance. OBJECTIVE: To study the prevalence of neuropathy using different
      electrophysiological techniques in subjects with impaired glucose tolerance (IGT)
      and no other identifiable cause of neuropathy. MATERIALS AND METHODS: The study
      was conducted on 30 age-matched controls and 58 subjects with impaired oral
      glucose tolerance test (OGTT) attending diabetic awareness. Prediabetes was
      defined using World Health Organization (WHO) criteria. All subjects had normal
      glycosylated hemoglobin HbA (1c), vitamin B12 levels, and thyroid function.
      Neuropathy was evaluated by nerve conduction studies (NCS) performed on one upper
      and both lower limbs, dorsal sural nerve, medial and lateral planter nerve
      conductions using conventional techniques. Neuropathy was also evaluated by
      autononic function tests, and quantitative sensory testing (QST). The subjects
      were followed up for 4 years. RESULTS: Out of 58 subjects, 19 (32.8%) had
      neuropathy. Nerve conduction studies showed evidence of neuropathy in 14 (24.13%)
      subjects, autonomic neuropathy was detected in 8 (13.8%), and QST was found to be
      abnormal in 16 (27.6%) subjects. Twenty subjects (34.5%) developed diabetes
      mellitus in the follow-up period. CONCLUSIONS: Neuropathy was detected in 32.8%
      subjects with IGT. Small fiber neuropathy was most common. Of all the three
      parameters studied, QST was found to be most sensitive technique for the
      detection of neuropathy. Assessment of medial plantar and dorsal sural NCS
      increases the sensitivity in the detection of neuropathy.

PMID- 25591681
TI  - Paralytic rabies: MRI findings and review of literature.
AB  - Paralytic rabies closely simulates Guillain-Barre syndrome or ascending myelitis
      often causing clinical dilemma. Two such patients were managed in our hospital
      whose magnetic resonance imaging (MRI) revealed characteristic findings revealing
      T2 hyper intensity in central spinal cord and in posterior brainstem and
      hypothalamus. These MRI findings are helpful in the diagnosis of rabies in
      appropriate setting. We also review the literature on MRI changes in paralytic
      rabies. 

PMID- 25591682
TI  - Operative nuances of excision of colloid cysts in septum pellucidum: a report of
      three cases.
AB  - Colloid cysts are common cysts are often located in the anterior third ventricle
      and septum pellucidum location is extremely rare. Cysts in septum pellucidum can
      be missed at surgery because of their unusual location. We describe three
      patients with colloid cysts in the septum pellucidum, with two in the cavum
      septum pellucidum. Various surgical implications of this unusual location are
      enumerated. 

PMID- 25591683
TI  - Primary intracranial peripheral PNET"--a case report and review.
AB  - The site of origin of primitive neuroectodermal tumors (PNETs) is quite varied
      and has significant influence on the prognosis. We report a case of intracranial
      peripheral PNET/Ewing's sarcoma arising from the superior tentorial surface in a
      13-year-old girl. Gross total excision of the tumor was done. We have discussed
      the distinction between central nervous system PNET (CNS PNET) and Intracranial
      Peripheral PNET (pPNET/ES) as their treatment and prognosis varies radically. A
      review of literature shows that prognosis is better in intracranial pPNET/ES. 

PMID- 25591684
TI  - Cerebral venous sinus thrombosis with increased factor VIII activity in an adult
      with iron deficiency anemia.

PMID- 25591685
TI  - Multi-centric spinal extradural malignant peripheral nerve sheath tumor: a case
      report.

PMID- 25591686
TI  - Angiocentric glioma: a treatable cause of epilepsy: report of a rare case.

PMID- 25591688
TI  - Cluster-like headache as presenting feature of Vogt-Koyanagi-Harada disease.

PMID- 25591687
TI  - Yolk sac tumor of the temporal bone: an unusual presentation as hydrocephalus.

PMID- 25591689
TI  - Diffusion restriction in pons resembling "reverse moustache" in dengue
      encephalitis.

PMID- 25591690
TI  - Primary central nervous system histiocytic sarcoma mimicking glioma.

PMID- 25591691
TI  - Absence status after starting clobazam in a patient with syndrome of continuous
      spike and wave during slow sleep (CSWS).

PMID- 25591692
TI  - Spinal metastasis presenting as adult tethered cord syndrome.

PMID- 25591693
TI  - Systemic lupus erythematosus and subarachnoid hemorrhage.

PMID- 25591694
TI  - First case report of caissons disease with pneumobilia.

PMID- 25591695
TI  - Intraventricular hemorrhage--unusual presentation of central neurocytoma.

PMID- 25591696
TI  - Intracranial granulocytic sarcomaina in a non-leukemia patient.

PMID- 25591697
TI  - Cerebral venous sinus thrombosis: an unusual initial presentation of mucinous
      adenocarcinoma of stomach.

PMID- 25591698
TI  - Giant extra-axial en-plaque tuberculoma with gyriform enhancement: unusual
      presentation of a common disease.

PMID- 25591699
TI  - Craniocervical pneumatization presenting as cranial nerve IX-XII palsies: case
      report and review of the literature.

PMID- 25591700
TI  - Spontaneous indirect CSF rhinorrhea following excision of a giant choroid plexus
      papilloma of lateral ventricle.

PMID- 25591701
TI  - Supratentorial parenchymal CNS melanocytoma--report of a rare case.

PMID- 25591702
TI  - Deep brain stimulation (DBS), lead migration, and the stimloc cap: complication
      avoidance.

PMID- 25591703
TI  - Non-terminal cervical myelocystocele: unusual cause of spastic quadriparesis in
      an adult.

PMID- 25591704
TI  - The triad of holocord syringomyelia, Chiari malformation and tethered cord:
      amelioration with simple detethering--a case for revisiting traction hypothesis?

PMID- 25591705
TI  - Virchow-Robin spaces producing visual field defect.

PMID- 25591706
TI  - Vertebral artery dissection and stroke after scuba diving.

PMID- 25591707
TI  - An unusual cause of low backache: lumbar interspinous bursitis.

PMID- 25591708
TI  - Acute transverse myelitis as the first clinical manifestation of systemic lupus
      erythematosus.

PMID- 25591709
TI  - Vanishing aneurysm during cerebral angiography complicating endovascular coiling:
      an unusual manifestation of intraoperative vasospasm.

PMID- 25591710
TI  - Determinants of percent expenditure of household income due to childhood
      diarrhoea in rural Bangladesh.
AB  - There is limited information on percent expenditure of household income due to
      childhood diarrhoea especially in rural Bangladesh. A total of 4205 children aged
      <5 years with acute diarrhoea were studied. Percent expenditure was calculated as
      total expenditure for the diarrhoeal episode divided by monthly family income,
      multiplied by 100. Overall median percent expenditure was 3.04 (range 0.01
      94.35). For Vibrio cholerae it was 6.42 (range 0.52-82.85), for enterotoxigenic
      Escherichia coli 3.10 (range 0.22-91.87), for Shigella 3.17 (range 0.06-77.80),
      and for rotavirus 3.08 (range 0.06-48.00). In a multinomial logistic regression
      model, for the upper tertile of percent expenditure, significant higher odds were
      found for male sex, travelling a longer distance to reach hospital (?median of 4
      miles), seeking care elsewhere before attending hospital, vomiting, higher
      frequency of purging (?10 times/day), some or severe dehydration and stunting. V.
      cholerae was the highest and rotavirus was the least responsible pathogen for
      percent expenditure of household income due to childhood diarrhoea. 

PMID- 25591712
TI  - The biogeography of the Papio baboons: a GIS-based analysis of range
      characteristics and variability.
AB  - The Papio baboons are known for their ecological flexibility and wide geographic
      ranges, as well as their uncertain taxonomy. There have, however, been few
      systematic comparisons of the environments occupied by the 6 major Papio species,
      and how differences in range conditions and variability might affect their
      evolutionary ecology remains unknown. This paper uses geographical information
      system techniques to explore the environmental associations of all 6 major
      species. It argues that despite some small differences in the average conditions
      encountered by each, it is in fact variation within individual ranges that is
      most apparent. In fact, the differences between the environments occupied by
      adjacent troops in well-known national parks may be as large or larger than the
      average differences in the ranges of different species, and this may have
      important implications for baboon biogeography.

PMID- 25591711
TI  - Myostatin and IGF-I signaling in end-stage human heart failure: a qRT-PCR study.
AB  - BACKGROUND: Myostatin (Mstn) is a key regulator of heart metabolism and
      cardiomyocyte growth interacting tightly with insulin-like growth factor I (IGF
      I) under physiological conditions. The pathological role of Mstn has also been
      suggested since Mstn protein was shown to be upregulated in the myocardium of end
      stage heart failure. However, no data are available about the regulation of gene
      expression of Mstn and IGF-I in different regions of healthy or pathologic human
      hearts, although they both might play a crucial role in the pathomechanism of
      heart failure. METHODS: In the present study, heart samples were collected from
      left ventricles, septum and right ventricles of control healthy individuals as
      well as from failing hearts of dilated (DCM) or ischemic cardiomyopathic (ICM)
      patients. A comprehensive qRT-PCR analysis of Mstn and IGF-I signaling was
      carried out by measuring expression of Mstn, its receptor Activin receptor IIB
      (ActRIIB), IGF-I, IGF-I receptor (IGF-IR), and the negative regulator of Mstn miR
      208, respectively. Moreover, we combined the measured transcript levels and
      created complex parameters characterizing either Mstn- or IGF-I signaling in the
      different regions of healthy or failing hearts. RESULTS: We have found that in
      healthy control hearts, the ratio of Mstn/IGF-I signaling was significantly
      higher in the left ventricle/septum than in the right ventricle. Moreover, Mstn
      transcript levels were significantly upregulated in all heart regions of DCM but
      not ICM patients. However, the ratio of Mstn/IGF-I signaling remained increased
      in the left ventricle/septum compared to the right ventricle of DCM patients
      (similarly to the healthy hearts). In contrast, in ICM hearts significant
      transcript changes were detected mainly in IGF-I signaling. In parallel with
      these results miR-208 showed mild upregulation in the left ventricle of both DCM
      and ICM hearts. CONCLUSIONS: This is the first demonstration of a spatial
      asymmetry in the expression pattern of Mstn/IGF-I in healthy hearts, which is
      likely to play a role in the different growth regulation of left vs. right
      ventricle. Moreover, we identified Mstn as a massively regulated gene in DCM but
      not in ICM as part of possible compensatory mechanisms in the failing heart.

PMID- 25591714
TI  - The University of Pennsylvania curriculum for training otorhinolaryngology
      residents in transoral robotic surgery.
AB  - PURPOSE: To define a curriculum for the development of robotic surgical skills in
      otorhinolaryngology residency training. METHODS: A systematic review of the
      current literature on robotic surgery training was performed. Based on prior
      reports in other specialties, a curriculum for otorhinolaryngology residents was
      created that progresses through several modules, including didactics, inanimate
      skills laboratory, and operative experience. RESULTS: The curriculum for
      residents in otorhinolaryngology was designed as follows: didactics include an
      overview of the robotic device and instruments, a tutorial in basic controls and
      function, and a room setup and positioning. The anatomy and steps of transoral
      procedures are taught through books, videos, operative observations, and cadaver
      dissections. Skills are developed with a virtual reality robotic simulator and
      robotics labs. The operative experience progresses from case observation to
      bedside assistant to console surgeon. The role of the console surgeon progresses
      in a stepwise fashion, and the procedures of radical tonsillectomy, supraglottic
      partial laryngectomy, and base of tongue resection have been organized as a
      series of steps. CONCLUSION: A structured curriculum for training residents in
      transoral robotic surgery was developed. This training is important for
      otorhinolaryngology residents to acquire the knowledge and skills to perform
      robotic surgery safely.

PMID- 25591715
TI  - Vitamin E and risk of age-related cataract: a meta-analysis.
AB  - OBJECTIVE: We conducted a meta-analysis to evaluate the relationship between
      vitamin E and age-related cataract (ARC). DESIGN: The fixed- or random-effect
      model was selected based on heterogeneity. Meta-regression was used to explore
      potential sources of between-study heterogeneity. Publication bias was evaluated
      using Begg's test. The dose-response relationship was assessed by a restricted
      cubic spline model. SETTING: Relevant studies were identified by a search of
      PubMed and the Cochrane Library to May 2014, without language restrictions.
      SUBJECTS: Studies involved samples of people of all ages. RESULTS: Dietary
      vitamin E intake, dietary and supplemental vitamin E intake, and high serum
      tocopherol levels were significantly associated with decreased risk of ARC, the
      pooled relative risk was 0.73 (95% CI 0.58, 0.92), 0.86 (95% CI 0.75, 0.99) and
      0.77 (95% CI 0.66, 0.91), respectively. Supplemental vitamin E intake was non
      significantly associated with ARC risk (relative risk=0.92; 95% CI 0.78, 1.07).
      The findings from dose-response analysis showed evidence of a non-linear
      association between dietary vitamin E intake and ARC. The risk of ARC decreased
      with dietary vitamin E intake from 7 mg/d (relative risk=0.94; 95% CI 0.90,
      0.97). CONCLUSIONS: The findings of the meta-analysis indicated that dietary
      vitamin E intake, dietary and supplemental vitamin E intake, and high level of
      serum tocopherol might be significantly associated with reduced ARC risk.

PMID- 25591713
TI  - Complete genome sequencing and phylogenetic analysis of dengue type 1 virus
      isolated from Jeddah, Saudi Arabia.
AB  - BACKGROUND: Dengue viruses (DENVs) are mosquito-borne viruses which can cause
      disease ranging from mild fever to severe dengue infection. These viruses are
      endemic in several tropical and subtropical regions. Multiple outbreaks of DENV
      serotypes 1, 2 and 3 (DENV-1, DENV-2 and DENV-3) have been reported from the
      western region in Saudi Arabia since 1994. Strains from at least two genotypes of
      DENV-1 (Asia and America/Africa genotypes) have been circulating in western Saudi
      Arabia until 2006. However, all previous studies reported from Saudi Arabia were
      based on partial sequencing data of the envelope (E) gene without any reports of
      full genome sequences for any DENV serotypes circulating in Saudi Arabia.
      FINDINGS: Here, we report the isolation and the first complete genome sequence of
      a DENV-1 strain (DENV-1-Jeddah-1-2011) isolated from a patient from Jeddah, Saudi
      Arabia in 2011. Whole genome sequence alignment and phylogenetic analysis showed
      high similarity between DENV-1-Jeddah-1-2011 strain and D1/H/IMTSSA/98/606
      isolate (Asian genotype) reported from Djibouti in 1998. Further analysis of the
      full envelope gene revealed a close relationship between DENV-1-Jeddah-1-2011
      strain and isolates reported between 2004-2006 from Jeddah as well as recent
      isolates from Somalia, suggesting the widespread of the Asian genotype in this
      region. CONCLUSIONS: These data suggest that strains belonging to the Asian
      genotype might have been introduced into Saudi Arabia long before 2004 most
      probably by African pilgrims and continued to circulate in western Saudi Arabia
      at least until 2011. Most importantly, these results indicate that pilgrims from
      dengue endemic regions can play an important role in the spread of new DENVs in
      Saudi Arabia and the rest of the world. Therefore, availability of complete
      genome sequences would serve as a reference for future epidemiological studies of
      DENV-1 viruses.

PMID- 25591716
TI  - Use of 11C-Choline positron emission tomography/computed tomography to
      investigate the mechanism of choline metabolism in lung cancer.
AB  - The present study was conducted to investigate the 11C-Choline metabolic
      mechanism and examine the association between 11C-Choline metabolism and uptake
      in different pathological types of lung cancer. A total of 18 tumor specimens and
      corresponding normal lung tissues were collected from patients who were diagnosed
      with lung cancer using 11C-Choline positron emission tomography (PET)/computed
      tomography (CT) imaging between January 2007 and December 2008 at the Medical
      Imaging Center of the Provincial Hospital Affiliated to Shandong University. The
      diagnosis was further confirmed pathologically following surgery. Reverse
      transcription polymerase chain reaction and western blotting were used to
      investigate the expression of choline acetyltransferase (ChAT) and choline kinase
      alpha (ChoK) in lung cancer tissue and normal lung tissue. The 11C-Choline PET/CT
      data were analyzed visually and semiquantitatively. Compared with the expression
      in the normal lung tissues, the mRNA and protein expression of ChAT and ChoK
      increased in nine and 14 of the 18 lung tumors, respectively. A total of eight of
      the 18 tumors exhibited significantly increased expression, while three exhibited
      no expression of ChoK and ChAT. All lung cancer lesions were visualized with 11C
      Choline PET/CT imaging. The phosphorylation and acetylation pathways of choline
      metabolism may be important in 11C-Choline uptake and metabolism in different
      pathological types of lung cancer.

PMID- 25591718
TI  - Temporal trends and risk factors for readmission for infections, gastrointestinal
      and immobility complications after an incident hospitalisation for stroke in
      Scotland between 1997 and 2005.
AB  - BACKGROUND: Improvements in stroke management have led to increases in the
      numbers of stroke survivors over the last decade and there has been a
      corresponding increase of hospital readmissions after an initial stroke
      hospitalisation. The aim of this study was to examine the one year risk of having
      a readmission due to infective, gastrointestinal or immobility (IGI)
      complications and to identify temporal trends and any risk factors. METHODS:
      Using a cohort of first hospitalised for stroke patients who were discharged
      alive, time to first event (readmission for IGI complications or death) within 1
      year was analysed in a competing risks framework using cumulative incidence
      methods. Regression on the cumulative incidence function was used to model the
      risks of having an outcome using the covariates age, sex, socioeconomic status,
      comorbidity, discharge destination and length of hospital stay. RESULTS: There
      were a total of 51,182 patients discharged alive after an incident stroke
      hospitalisation in Scotland between 1997-2005, and 7,747 (15.1%) were readmitted
      for IGI complications within a year of the discharge. Comparing incident stroke
      hospitalisations in 2005 with 1997, the adjusted risk of IGI readmission did not
      increase (HR = 1.00 95% CI (0.90, 1.11). However, there was a higher risk of IGI
      readmission with increasing levels of deprivation (most deprived fifth vs. least
      deprived fifth HR = 1.16 (1.08, 1.26). CONCLUSIONS: Approximately 15 in 100
      patients discharged alive after an incident hospitalisation for stroke in
      Scotland between 1997 and 2005 went on to have an IGI readmission within one
      year. The proportion of readmissions did not change over the study period but
      those living in deprived areas had an increased risk.

PMID- 25591720
TI  - CORRIGENDUM: Formation mechanism and optimization of highly luminescent N-doped
      graphene quantum dots.

PMID- 25591719
TI  - Augmented pentose phosphate pathway plays critical roles in colorectal
      carcinomas.
AB  - Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated
      in cancer cells. Accumulating evidence indicated the significance of the altered
      glucose metabolism in cancer, but the implication for oncotherapy remains
      unclear. Here we report that the synthesis of glycolytic and PPP enzymes is
      almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The
      mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical
      Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128
      (150-600 nM) and resveratrol (75-300 MUM) inhibited aerobic glycolysis in the
      cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP(+)
      ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os
      administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth
      and delayed tumor formation by transplantable CRC specimens derived from
      patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a
      promising therapeutic strategy against CRCs.

PMID- 25591722
TI  - Tailoring of energy levels in D-pi-A organic dyes via fluorination of acceptor
      units for efficient dye-sensitized solar cells.
AB  - A molecular design is presented for tailoring the energy levels in D-pi-A organic
      dyes through fluorination of their acceptor units, which is aimed at achieving
      efficient dye-sensitized solar cells (DSSCs). This is achieved by exploiting the
      chemical structure of common D-pi-A organic dyes and incorporating one or two
      fluorine atoms at the ortho-positions of the cyanoacetic acid as additional
      acceptor units. As the number of incorporated fluorine atoms increases, the LUMO
      energy level of the organic dye is gradually lowered due to the electron
      withdrawing effect of fluorine, which ultimately results in a gradual reduction
      of the HOMO-LUMO energy gap and an improvement in the spectral response.
      Systematic investigation of the effects of incorporating fluorine on the
      photovoltaic properties of DSSCs reveals an upshift in the conduction-band
      potential of the TiO2 electrode during impedance analysis; however, the
      incorporation of fluorine also results in an increased electron recombination
      rate, leading to a decrease in the open-circuit voltage (Voc). Despite this
      limitation, the conversion efficiency is gradually enhanced as the number of
      incorporated fluorine atoms is increased, which is attributed to the highly
      improved spectral response and photocurrent. 

PMID- 25591721
TI  - High dose intravenous colistin methanesulfonate therapy is associated with high
      rates of nephrotoxicity; a prospective cohort study from Saudi Arabia.
AB  - BACKGROUND: Nephrotoxicity is an important adverse effect of colistin
      methanesulfonate (CMS) therapy. No data exist on rates and risk factors for
      colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective
      cohort study to identify rates and risk factors for CMS nephrotoxicity in our
      patient population. METHODS: We prospectively included adult patients who
      received >=48 hours of intravenous CMS therapy. Pregnant patients and those on
      renal replacement were excluded. Patients received 9 million units (mU) loading
      dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted
      according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined
      as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease).
      Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New
      York, USA). The study was approved by the institution's Research Ethics
      Committee. RESULTS: A total of 67 patients were included in the study. Mean (+/
      standard deviation) age was 57.5 (+/-24.0) years, Charlson Co-morbidity Score
      2.88 (+/-2.39), CrCl 133.60 (+/-92.54) mL/min and serum albumin 28.65 (+/-4.45)
      g/L. Mean CMS dose was 0.11 (+/-0.04) mU/kg/day and mean total CMS dose received
      was 101.21 (+/-47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined
      nephrotoxicity. Mean total CMS dose and duration of therapy before onset of
      nephrotoxicity were 66.71 (+/-43.45) mU and 8.70 (+/-6.70) days, respectively. In
      bivariate analysis, patients with nephrotoxicity were significantly older (P
      0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic
      regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence
      interval (CI) 0.57-0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI
      1.37-195.55; P 0.027) as independent risk factors for CMS nephrotoxicity.
      CONCLUSIONS: High dose intravenous CMS therapy is associated with high rates of
      nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were
      baseline hypoalbuminemia and intensive care admission.

PMID- 25591723
TI  - Fast atrial activity predicts recurrence of atrial fibrillation after pulmonary
      vein isolation: results from a prospective randomized study.
AB  - BACKGROUND: Recurrence of atrial fibrillation (AF) after ablative treatment is
      common. We hypothesized that AF recurrence is heralded by fast ectopic atrial
      activity occurring after electrical reconnection of previously isolated pulmonary
      veins. METHODS: Patients with paroxysmal or persistent AF undergoing pulmonary
      vein isolation (PVI) were followed up by 24-h Holter monitoring every 3 months
      for the first year and every 6 months thereafter. Antiarrhythmic drugs were
      withdrawn after a blanking period of 4 weeks for paroxysmal and 3 months for
      persistent AF. Ectopic atrial activity was defined as a burden of atrial
      extrasystoles >5% of the total QRS number. Fast atrial activity was present if
      mean cycle length of ectopic atrial activity was shorter than 50% of the mean
      cycle length of sinus rhythm in the last ten heartbeats. Patients with
      symptomatic fast atrial activity but without AF recurrence were randomized to
      undergo a second PVI procedure or resume antiarrhythmic medication. During follow
      up, a 24-h Holter recording was performed every 3 months. Additionally, a 7-day
      external loop recording was performed in every pt with palpitations and no AF or
      ectopic atrial activity in the 24-h Holter. RESULTS: One hundred twenty-four pts
      with AF (88 paroxysmal, 36 persistent) developed fast atrial activity 6 +/- 3
      months after PVI. Twenty-two pts were asymptomatic and eight pts refused
      randomization. Ninety-four pts (61 men, age 57 +/- 12 years) were randomized to
      either receive a second PVI procedure (group I, 48 pts) or antiarrhythmic
      medication (group II, 46 pts). Re-PVI in group I was performed 10 +/- 8 months
      after the first PVI. During a follow-up of 20 +/- 6 months, 11 pts of group I
      (23%) and 43 pts of group II (93%) had recurrence of AF. The mean time of AF
      recurrence after appearance of fast atrial activity was 4 +/- 2 in group I and 5
      +/- 3 months in group II. CONCLUSIONS: In patients with atrial fibrillation and
      after the first PVI procedure, appearance of symptomatic fast atrial activity is
      associated with a high risk of AF recurrence. Re-isolation of reconnected
      pulmonary veins in these pts significantly reduces the risk of AF recurrence.

PMID- 25591724
TI  - Ventricular fibrillation: are swine a sensitive species?
AB  - PURPOSE: Legislation and sentiment have pushed large-animal electrophysiological
      research from the canine to the swine model. Anecdotal experience suggests that
      the swine is particularly sensitive to ventricular fibrillation (VF) induction,
      and radiofrequency ablation studies are consistent with this. Currently, no data
      exist directly comparing the VF threshold (VFT) in humans to swine. Because of
      the perceived difference in vulnerability to VF induction, we hypothesized that
      the VFT would be lower in swine compared to humans. METHODS: Six anesthetized
      open-chested swine, 31 +/- 2 kg, were studied that were part of an ongoing study
      with up to 6 h of previous closed-chest percutaneous pacing with repeated VF
      cycles. Similar to the human study of Horowitz et al., 24 pulses of 4 ms each
      were applied at a rate of 100 Hz during the ST segment to the epicardium via a
      pair of 7-mm diameter platinum electrodes whose centers were 15 mm apart. Current
      was increased until VF was induced. RESULTS: The swine right ventricle (RV) VFT
      was 9.7 +/- 2.1 mA [median = 9.0, interquartile range (IQR) = 7.8-12.0], and the
      left ventricle (LV) VFT was 10.7 +/- 2.2 mA [median = 10.5, IQR = 8.8-12.5] (p =
      NS). Horowitz reported the RV VFT in six patients as 24.3 +/- 5.2 mA [median =
      24.5, IQR = 19.0-29.3] and the LV VFT in ten patients as 33.6 +/- 9.5 mA [median
      = 36.5, IQR = 27.3-42.3] (p = .11). Both the RV and LV VFTs were lower for swine
      (p < 0.003), and each of the mean and median VFTs for the ventricles together was
      one third that of the humans. CONCLUSIONS: Swine are about three times as
      sensitive to the electrical induction of VF as are humans.

PMID- 25591725
TI  - Improvement of the myocardial performance index in atrial fibrilation patients
      treated with amiodarone after cardioversion.
AB  - PURPOSE: This study evaluated the response to electrical cardioversion (EC) and
      the effect on the myocardial performance index (MPI) in patients with persistent
      and long-standing persistent atrial fibrillation (AF). METHODS: We enrolled 103
      patients (mean age 69.6 +/- 8.9 years, 40.7% males) with a diagnosis of
      persistent and long-standing persistent AF. EC was applied to all patients after
      one g of amiodarone administration. Echocardiographic findings before EC were
      compared in patients with successful versus unsuccessful cardioversions and in
      patients with maintained sinus rhythm (SR) versus those with AF recurrence at the
      end of the first month. We also compared echocardiographic data before EC versus
      at the end of the first month in the same patients with maintained SR. RESULTS:
      SR was achieved in 72.8% of patients and was continued at the end of the first
      month in 69.3% of the patients. The MPI value of all patients was found to be
      0.73 +/- 0.21. The size of the left atrium was determined to be an independent
      predictor of the maintenance of SR at 1 month. In subgroup analyses, when we
      compared echocardiographic findings before EC and at the end of the first month
      in patients with maintained SR, the MPI (0.66 +/- 0.14 vs 0.56 +/- 0.09, p <
      0.001) values were significantly decreased. CONCLUSIONS: Our study is the first
      to show impairment of the MPI, which is an indicator of systolic and diastolic
      function, in patients with persistent and long-standing persistent AF and
      improvement of the MPI after successful EC.

PMID- 25591726
TI  - Three-dimensional rotational venography of the coronary sinus tree facilitates
      left ventricular lead implantation for CRT.
AB  - BACKGROUND: Precise knowledge of the coronary sinus (CS) tree anatomy facilitates
      catheter-based intubation of the CS, target vein and lead selection and reduces
      the need for fluoroscopy, contrast medium and overall procedure time in cardiac
      resynchronization therapy (CRT). Three-dimensional rotational angiography (3DRA)
      provides a new means of multiangle imaging of the CS tree that can be applied
      preoperatively. PURPOSE AND METHODS: Our study aims to investigate the
      feasibility of preoperative rotational CS venography and its implications for CRT
      device implantation procedures. For this purpose, CS visualization was done
      either conventionally with retrograde CS venography and standard fluoroscopic
      views (SFV, n = 30), or with antegrade CS imaging via contrast medium injection
      into the left coronary artery using 3DRA in the venous phase of contrast flow
      (3DRA, n = 30). RESULTS: 3DRA successfully identified the posterior and left
      marginal veins in 92% of patients and allowed target vein visualization in 86%.
      Additional retrograde venography was necessary in four patients (14%).
      Fluoroscopy time and contrast medium administration for stable CS intubation were
      lower in the group with 3DRA than in those with SFV (all p < 0.05). The time for
      CS lead placement after guiding catheter intubation was 8.9 +/- 5.5 min in the
      3DRA group versus 14.7 +/- 7.4 min in SFV patients (p < 0.05). Consequently,
      total fluoroscopy time (-12.1 min), volume of contrast medium (-29.5 ml) and
      overall procedure time (-32.8 min) were significantly lower in 3DRA than in SFV
      patients (p < 0.05). CONCLUSION: 3DRA offers reliable multiangle visualization of
      the CS anatomy and facilitates successful CRT lead implantation.

PMID- 25591728
TI  - Exploring local immune responses to vaccines using efferent lymphatic
      cannulation.
AB  - The early stages of the induction of a primary immune response to a vaccine can
      shape the overall quality of the immune memory generated and hence affect the
      success of the vaccine. This early interaction between a vaccine and the immune
      system occurs first at the site of vaccination and can be explored using afferent
      cannulation. Subsequently, the vaccine and adjuvant activates the local draining
      lymph node. These interactions can be studied in real time in vivo using efferent
      lymphatic duct cannulation in large animal models and are the subject of this
      review. Depending on how the vaccine is delivered, the draining lymph nodes of
      different organs can be accessed, facilitating the testing of tissue-specific
      vaccinations. The efferent lymphatic cannulation model provides an avenue to
      study the effect of both adjuvants and antigen on the local immune system, and
      hence opens a pathway toward developing more effective ways of inducing immunity.

PMID- 25591727
TI  - Autoimmune disease-associated variants of extracellular endoplasmic reticulum
      aminopeptidase 1 induce altered innate immune responses by human immune cells.
AB  - Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been
      linked to several autoimmune diseases; however, the molecular mechanisms
      underlying these associations are not well understood. Recently, we demonstrated
      that ERAP1 regulates key aspects of the innate immune response. Previous studies
      show ERAP1 to be endoplasmic reticulum-localized and secreted during
      inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic
      variants may have in modulating the innate immune responses of human peripheral
      blood mononuclear cells (hPBMCs) using two experimental methods: extracellular
      exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression.
      We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1
      overexpression by Ad5 vectors increased inflammatory cytokine and chemokine
      production, and enhanced immune cell activation. Investigating the molecular
      mechanisms behind these responses revealed that ERAP1 is able to activate innate
      immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin
      domain-containing 3) inflammasome. Importantly, these responses varied if
      autoimmune disease-associated variants of ERAP1 were examined in the assay
      systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1beta
      production. To our knowledge, this is the first report identifying ERAP1 as being
      involved in modulating innate responses of human immune cells, a finding that may
      explain why ERAP1 has been genetically associated with several autoimmune
      diseases.

PMID- 25591729
TI  - Violence against children, later victimisation, and mental health: a cross
      sectional study of the general Norwegian population.
AB  - BACKGROUND: Violence in childhood is associated with mental health problems and
      risk of revictimisation. Less is known about the relative importance of the
      various types of childhood and adult victimisation for adult mental health.
      OBJECTIVE: To estimate the associations between various types of childhood and
      adult violence exposure, and their combined associations to adult mental health.
      METHOD: This study was a cross-sectional telephone survey of the Norwegian adult
      population; 2,435 women and 2,092 men aged 18-75 participated (19.3% of those we
      tried to call and 42.9% of those who answered the phone). The interview comprised
      a broad array of violence exposure in both childhood and adulthood.
      Anxiety/depression was measured by the Hopkins Symptom Check List (HSCL-10).
      RESULTS: Victimisation was commonly reported, for example, child sexual abuse
      (women: 10.2%, men: 3.5%), childhood-parental physical violence (women: 4.9%,
      men: 5.1%), and lifetime forcible rape (women: 9.4%, men: 1.1%). All categories
      of childhood violence were significantly associated with adult victimisation,
      with a 2.2-5.0 times higher occurrence in exposed children (p<0.05 for all
      associations). Anxiety/depression (HSCL-10) associated with adult abuse increased
      with the number of childhood violence categories experienced (p<0.001). All
      combinations of childhood violence were significantly associated with
      anxiety/depression (p<0.001 for all associations). Individuals reporting
      psychological violence/neglect had the highest levels of anxiety/depression.
      CONCLUSIONS: RESULTS should be interpreted in light of the low response rate.
      Childhood violence in all its forms was a risk factor for victimisation in
      adulthood. Adult anxiety/depression was associated with both the number of
      violence categories and the type of childhood violence experienced. A broad
      assessment of childhood and adult violence exposure is necessary both for
      research and prevention purposes. Psychological violence and neglect should
      receive more research attention, especially in combination with other types of
      violence.

PMID- 25591730
TI  - Assessment of competence in simulated flexible bronchoscopy using motion
      analysis.
AB  - BACKGROUND: Flexible bronchoscopy should be performed with a correct posture and
      a straight scope to optimize bronchoscopy performance and at the same time
      minimize the risk of work-related injuries and endoscope damage. OBJECTIVES: We
      aimed to test whether an automatic motion analysis system could be used to
      explore if there is a correlation in scope movements and the operator's level of
      experience. Our hypothesis was that experienced bronchoscopists move less and
      keep the flexible scope straighter than less-experienced bronchoscopists while
      performing procedures. METHODS: Eleven novices, 9 intermediates and 9 experienced
      bronchoscopy operators performed 3 procedures each on a bronchoscopy simulator.
      The Microsoft Kinect system was used to automatically measure the total deviation
      of the scope from a perfectly straight, vertical line. RESULTS: The low-cost
      motion analysis system could measure the accumulated deviation of the scope
      precisely during the procedure. The deviations were greatest for the novices and
      smallest for the most experienced operators for all 3 procedures (p = 0.01, p =
      0.01 and p = 0.04, respectively). The total deviation from the straight scope
      correlated negatively with the performance on the simulator (virtual-reality
      simulator score; p < 0.001). CONCLUSION: The motion analysis system could
      discriminate between different levels of experience. Automatic feedback on
      correct movements during self-directed training on simulators might help new
      bronchoscopists learn how to handle the bronchoscope like an expert.

PMID- 25591731
TI  - Salvage surgery after chemotherapy with S-1 plus cisplatin for alpha-fetoprotein
      producing gastric cancer with a portal vein tumor thrombus: a case report.
AB  - BACKGROUND: Patient with alpha-Fetoprotein (AFP)-producing gastric cancer usually
      has a short survival time due to frequent hepatic and lymph node metastases.
      Gastric cancer with portal vein tumor thrombus (PVTT) is rare and has an
      extremely poor prognosis. CASE PRESENTATION: A 63-year-old man was found to have
      a huge Type 3 gastric cancer with a PVTT and a highly elevated serum AFP level.
      Chemotherapy with S-1 plus cisplatin was given to this patient with unresectable
      gastric cancer for 4 months. The serum AFP level decreased from 6,160 ng/mL to
      60.7 ng/mL with chemotherapy. Since the PVTT disappeared after the chemotherapy,
      the patient underwent total gastrectomy. Histological findings of the primary
      tumor after chemotherapy showed poorly differentiated adenocarcinoma without
      hepatoid cells and viable tumor cells remaining in less than 1/3 of the
      neoplastic area of mucosa and one lymph node. The cancerous cells were
      immunohistochemically stained by anti-AFP antibody. The patient has survived for
      48 month without recurrence. CONCLUSIONS: AFP-producing gastric cancer with a
      PVTT has an extremely poor prognosis, but long-term survival was achieved for
      this dismal condition by salvage surgery after chemotherapy.

PMID- 25591732
TI  - Cycloartan-24-ene-1alpha,2alpha,3beta-triol, a cycloartane-type triterpenoid from
      the resinous exudates of Commiphora myrrha, induces apoptosis in human prostatic
      cancer PC-3 cells.
AB  - Plant-derived antitumor drugs are currently used in chemotherapy. Cycloartane
      triterpenoids have shown a cytotoxic effect on human prostate cancer cells. The
      aim of the present study was to isolate a cycloartane triterpenoid from
      Commiphora myrrha and evaluate its anticancer potential. Cycloartan-24-ene
      1alpha,2alpha,3beta-triol (MY-1) was isolated from Commiphora myrrha, and its
      structure was determined through 1H and 13C nuclear magnetic resonance
      spectroscopy. The cytotoxic and apoptotic effects of MY-1 on human prostatic
      cancer PC-3 cells were estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis and terminal
      deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining assay, and
      the expression of apoptotic-related proteins were evaluated by western blotting.
      MY-1 showed cytotoxic activity on PC-3 cells in a concentration-dependent manner
      with an IC50 value of 9.6 uM at 24 h. MY-1 induced cell cycle arrest and
      apoptosis. Western blot analysis revealed that MY-1 regulated the expression
      levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), p53 and
      caspase-3 in the PC-3 cells. These findings indicate that MY-1 exerts
      significantly pro-apoptotic activity against human hormone-independent prostatic
      cancer and support MY-1 as a potential anticancer drug.

PMID- 25591733
TI  - Correlation of EEG slowing with cognitive domains in nondemented patients with
      Parkinson's disease.
AB  - BACKGROUND: Cognitive deficits in Parkinson's disease (PD) are heterogeneous and
      can be classified into cognitive domains. Quantitative EEG is related to and
      predictive of cognitive status in PD. In this cross-sectional study, the
      relationship of cognitive domains and EEG slowing in PD patients without dementia
      is investigated. METHODS: A total of 48 patients with idiopathic PD were
      neuropsychologically tested. Cognitive domain scores were calculated combining Z
      scores of test variables. Slowing of EEG was measured with median EEG frequency.
      Linear regression was used for correlational analyses and to control for
      confounding factors. RESULTS: EEG median frequency was significantly correlated
      to cognitive performance in most domains (episodic long-term memory, rho = 0.54;
      overall cognitive score, rho = 0.47; fluency, rho = 0.39; attention, rho = 0.37;
      executive function, rho = 0.34), but not to visuospatial functions and working
      memory. CONCLUSION: Global EEG slowing is a marker for overall cognitive
      impairment in PD and correlates with impairment in the domains attention,
      executive function, verbal fluency, and episodic long-term memory, but not with
      working memory and visuospatial functions. These disparate effects warrant
      further investigations.

PMID- 25591735
TI  - Erratum to: Surgical risk model for acute diffuse peritonitis based on a Japanese
      nationwide database: an initial report on the surgical and 30-day mortality.

PMID- 25591734
TI  - Astragaloside IV controls collagen reduction in photoaging skin by improving
      transforming growth factor-beta/Smad signaling suppression and inhibiting matrix
      metalloproteinase-1.
AB  - Exposure to ultraviolet (UV) light reduces levels of type I collagen in the
      dermis and results in human skin damage and premature skin aging (photoaging).
      This leads to a wrinkled appearance through the inhibition of transforming growth
      factor-beta (TGF-beta)/Smad signaling. UV irradiation increases type I collagen
      degradation through upregulating matrix metalloproteinase (MMP) expression.
      Astragaloside IV (AST) is one of the major active components extracted from
      Astragalus membranaceus. However, its multiple anti-photoaging effects remain to
      be elucidated. In the present study, the effects of AST against collagen
      reduction in UV-induced skin aging in human skin fibroblasts were investigated.
      The expression of type I procollagen (COL1), MMP-1, TGF-betaRII and Smad7 were
      determined using reverse transcription-polymerase chain reaction, western
      blotting and ELISA, respectively. UV irradiation inhibits type I collagen
      production by suppressing the TGF-beta/Smad signaling pathway and increasing COL1
      degradation by inducing MMP-1 expression. Transforming growth factor-beta type II
      protein and COL1 mRNA decreased but MMP-1 and Smad7 levels increased in the
      photoaging model group, which was reversed by topical application of AST. AST
      prevents collagen reduction from UV irradiation in photoaging skin by improving
      TGF-beta/Smad signaling suppression and inhibiting MMP-1, thus AST may be a
      potential agent against skin photoaging.

PMID- 25591736
TI  - LAMC2 enhances the metastatic potential of lung adenocarcinoma.
AB  - Lung cancer is the number one cancer killer, and metastasis is the main cause of
      high mortality in lung cancer patients. However, mechanisms underlying the
      development of lung cancer metastasis remain unknown. Using genome-wide
      transcriptional analysis in an experimental metastasis model, we identified
      laminin gamma2 (LAMC2), an epithelial basement membrane protein, to be
      significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2
      increased traction force, migration, and invasion of lung adenocarcinoma cells
      accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2
      knockdown decreased traction force, migration, and invasion accompanied by EMT
      reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration
      and invasion via EMT that was integrin beta1- and ZEB1-dependent. High LAMC2 was
      significantly correlated with the mesenchymal marker vimentin expression in lung
      adenocarcinomas, and with higher risk of recurrence or death in patients with
      lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung
      adenocarcinoma via EMT and may be a potential therapeutic target. 

PMID- 25591739
TI  - The state of cartilage regeneration: current and future technologies.
AB  - It is clear that mature human articular cartilage does not have the innate
      ability to regenerate. Due to this, much effort has been put forth to work on
      bestowing this ability. While early data focused on more basic outcomes such as
      percentage of defect fill, the tissue formed was a "cartilage scar" or "hyaline
      like" tissue. Even with more advanced technologies, it is clear that no current
      procedure is able to reconstitute the native structure and function of true
      hyaline cartilage. As research advancement has somewhat plateaued in this regard,
      it is crucial that future work focuses on a multifactorial approach, treating the
      joint as an organ system. The purpose of this review is to update readers on the
      most recent literature and controversies surrounding articular cartilage
      regeneration. Specific focus will be placed on current technologies available in
      the USA and the basic science to support them. 

PMID- 25591737
TI  - Parkin maintains mitochondrial levels of the protective Parkinson's disease
      related enzyme 17-beta hydroxysteroid dehydrogenase type 10.
AB  - Mutations of the PARK2 and PINK1 genes, encoding the cytosolic E3 ubiquitin
      protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1,
      respectively, cause autosomal recessive early-onset Parkinson's disease (PD).
      Parkin and PINK1 cooperate in a biochemical mitochondrial quality control pathway
      regulating mitochondrial morphology, dynamics and clearance. This study
      identifies the multifunctional PD-related mitochondrial matrix enzyme 17-beta
      hydroxysteroid dehydrogenase type 10 (HSD17B10) as a new Parkin substrate. Parkin
      overproduction in cells increased mitochondrial HSD17B10 abundance by a mechanism
      involving ubiquitin chain extension, whereas PARK2 downregulation or deficiency
      caused mitochondrial HSD17B10 depletion in cells and mice. HSD17B10 levels were
      also found to be low in the brains of PD patients with PARK2 mutations. Confocal
      and Forster resonance energy transfer (FRET) microscopy revealed that HSD17B10
      recruited Parkin to the translocase of the outer membrane (TOM), close to PINK1,
      both in functional mitochondria and after the collapse of mitochondrial membrane
      potential (DeltaPsim). PD-causing PARK2 mutations impaired interaction with
      HSD17B10 and the HSD17B10-dependent mitochondrial translocation of Parkin.
      HSD17B10 overproduction promoted mitochondrial elongation and mitigated CCCP
      induced mitochondrial degradation independently of enzymatic activity. These
      effects were abolished by overproduction of the fission-promiting dynamin-related
      protein 1 (Drp1). By contrast, siRNA-mediated HSD17B10 silencing enhanced
      mitochondrial fission and mitophagy. These findings suggest that the maintenance
      of appropriate mitochondrial HSD17B10 levels is one of the mechanisms by which
      Parkin preserves mitochondrial quality. The loss of this protective mechanism may
      contribute to mitochondrial dysfunction and neuronal degeneration in autosomal
      recessive PD. 

PMID- 25591740
TI  - A revised monitor source method for practical deadtime count loss compensation in
      clinical planar and SPECT studies.
AB  - The aim of the study is to verify the fundamental assumption in the monitor
      source method, i.e. uniform fractional count loss across the field of view (FOV),
      and to introduce a revised monitor source method for SPECT deadtime correction
      that minimally interferes with the clinical protocol. SPECT images of non-uniform
      phantoms (4GBq (99m)Tc) with and without monitor sources (2  *  20MBq (99m)Tc)
      attached to each detector were acquired nine times over 48 h in the photopeak
      energy window and the scatter energy window. Fractional count loss uniformity
      across the FOV was evaluated by correlating count rates in different regions of
      interest on projection images at different deadtime loss levels. The correction
      factors were calculated as the ratios of monitor source count rates with and
      without the phantom. Such factors were applied to the phantom images acquired
      without the monitor sources. The counting efficiency (count rate per unit
      activity) of the camera was calculated as a function of activity in the FOV both
      prior to and after the deadtime count-loss correction. The deadtime correction
      effectiveness was assessed by the independence of the efficiency on the activity
      in the FOV. Methods to interpolate the projection deadtime loss, based on limited
      projections, were also investigated. The fractional deadtime count loss was
      uniform across the FOV (r > 0.99). After the deadtime correction, the efficiency
      was largely independent of the activity in the FOV. The median and maximum
      absolute errors after the deadtime count loss correction were <=1% and ~2%,
      respectively. Measured deadtime loss from five views per detector can be used to
      estimate deadtime count loss with errors <=1% for all SPECT projections. The
      revised monitor source method can effectively correct planar and SPECT deadtime
      loss. Sparse sampling of the projection deadtime loss allows the acquisition of
      high monitor source counts with minimal time added while preserving the entire
      useful FOV.

PMID- 25591738
TI  - Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung
      cancer cells to cisplatin and restricts tumor growth.
AB  - MicroRNAs (miRs) regulate a variety of cellular processes, and their impaired
      expression is involved in cancer. Silencing of tumor-suppressive miRs in cancer
      can occur through epigenetic modifications, including DNA methylation and histone
      deacetylation. We performed comparative miR profiling on cultured lung cancer
      cells before and after treatment with 5'aza-deoxycytidine plus Trichostatin A to
      reverse DNA methylation and histone deacetylation, respectively. Several tens of
      miRs were strongly induced by such 'epigenetic therapy'. Two representatives, miR
      512-5p (miR-512) and miR-373, were selected for further analysis. Both miRs were
      secreted in exosomes. Re-expression of both miRs augmented cisplatin-induced
      apoptosis and inhibited cell migration; miR-512 also reduced cell proliferation.
      TEAD4 mRNA was confirmed as a direct target of miR-512; likewise, miR-373 was
      found to target RelA and PIK3CA mRNA directly. Our results imply that miR-512 and
      miR-373 exert cell-autonomous and non-autonomous tumor-suppressive effects in
      lung cancer cells, where their re-expression may benefit epigenetic cancer
      therapy. 

PMID- 25591741
TI  - Acoustic Radiation Force Impulse (ARFI) imaging for the distinction between
      benign and malignant thyroid nodules.
AB  - PURPOSE: The aim of the present study was to evaluate thyroid nodules using
      virtual touch quantification (VTQ) of force impulse acoustic radiation (ARFI)
      imaging and to investigate a cutoff value for the differentiation of malignant
      thyroid nodules. MATERIALS AND METHODS: Ninety-five patients with quantitatively
      assessed (VTQ) thyroid nodules were evaluated with ARFI imaging in this
      prospective study. ARFI imaging with VTQ was performed only on the nodules which
      were expected to undergo fine-needle aspiration biopsy (FNAB). All of the thyroid
      lesions were examined histopathologically. RESULTS: The mean shear wave velocity
      (SWV) value of the malignant nodules (3.18 +/- 0.39 m/s) was higher than that of
      the benign nodules (2.11 +/- 0.53 m/s). There was a statistically significant
      difference between the mean SWV values of benign and malignant nodules (p <
      0.001). A SWV cutoff value of greater than 2.66 m/s yielded sensitivity and
      specificity values of 100 and 82.3 %, respectively, for diagnosis of malignant
      nodules. CONCLUSION: VTQ of ARFI imaging has high sensitivity and specificity for
      discriminating between benign and malignant thyroid nodules and may positively
      contribute to clinical evaluation of these nodules.

PMID- 25591747
TI  - Erosive tooth wear and wedge-shaped defects in 1996 and 2006: cross- sectional
      surveys of Swiss army recruits.
AB  - The purpose of this study was to determine the prevalence and possible
      etiological factors of erosive tooth wear and wedge-shaped defects in Swiss Army
      recruits and compare the findings with those of an analogous study conducted in
      1996. In 2006, 621 recruits between 18 and 25 years of age (1996: 417 recruits;
      ages 19 to 25) were examined for erosive tooth wear and wedge-shaped defects.
      Additional data was acquired using a questionnaire about personal details,
      education, dentition?s subjective condition, oral hygiene, eating and drinking
      habits, medications used, and general medical problems. In 2006, 60.1% of those
      examined exhibited occlusal erosive tooth wear not involving the dentin (1996:
      82.0%) and 23.0% involving the dentin (1996: 30.7%). Vestibular erosive tooth
      wear without dentin involvement was seen in 7.7% in 2006 vs. 14.4% in 1996.
      Vestibular erosive tooth wear with dentin involvement was rare in both years
      (0.5%). Oral erosive tooth wear lacking exposed dentin was also rare in those
      years, although more teeth were affected in 2006 (2.1%) than in 1996 (0.7%). The
      examinations in 2006 found one or more initial wedge-shaped lesions in 8.5% of
      the recruits, while 20.4% of the study participants exhibited such in 1996. In
      1996, 53% consumed acidic foods and beverages more than 5 times/day; in 2006,
      83.9% did so. In neither study did multivariate regression analyses show any
      significant correlations between occurrence and location of erosive tooth wear
      and wedge-shaped defects and various other parameters, e.g., eating and hygiene
      habits, or dentin hyper-sensitivity. Despite a significant increase in
      consumption of acidic products between 1996 and 2006, the latter study found both
      fewer erosive tooth wear and fewer wedge-shaped defects (i.e., fewer non-carious
      lesions.). 

PMID- 25591748
TI  - Mandatory imaging cuts costs and reduces the rate of unnecessary surgeries in the
      diagnostic work-up of patients suspected of having appendicitis.
AB  - OBJECTIVE: To evaluate whether mandatory imaging is an effective strategy in
      suspected appendicitis for reducing unnecessary surgery and costs. METHODS: In
      2010, guidelines were implemented in The Netherlands recommending the mandatory
      use of preoperative imaging to confirm/refute clinically suspected appendicitis.
      This retrospective study included 1,556 consecutive patients with clinically
      suspected appendicitis in 2008-2009 (756 patients/group I) and 2011-2012 (800
      patients/group II). Imaging use (none/US/CT and/or MRI) was recorded. Additional
      parameters were: complications, medical costs, surgical and histopathological
      findings. The primary study endpoint was the number of unnecessary surgeries
      before and after guideline implementation. RESULTS: After clinical examination by
      a surgeon, 509/756 patients in group I and 540/800 patients in group II were
      still suspected of having appendicitis. In group I, 58.5% received preoperative
      imaging (42% US/12.8% CT/3.7% both), compared with 98.7% after the guidelines
      (61.6% US/4.4% CT/ 32.6% both). The percentage of unnecessary surgeries before
      the guidelines was 22.9%. After implementation, it dropped significantly to 6.2%
      (p<0.001). The surgical complication rate dropped from 19.9% to 14.2%. The
      average cost-per-patient decreased by 594 <euro> from 2,482 to 1,888 <euro> (CL:
      1081; -143). CONCLUSION: Increased use of imaging in the diagnostic work-up of
      patients with clinically suspected appendicitis reduced the rate of negative
      appendectomies, surgical complications and costs. KEY POINTS: * The 2010 Dutch
      guidelines recommend mandatory imaging in the work-up of appendicitis. * This led
      to a considerable increase in the use of preoperative imaging. * Mandatory
      imaging led to reduction in unnecessary surgeries and surgical complications. *
      Use of mandatory imaging seems to reduce health care costs.

PMID- 25591746
TI  - Defining the orphan functions of lysine acetyltransferases.
AB  - Long known for their role in histone acetylation, recent studies have
      demonstrated that lysine acetyltransferases also carry out distinct "orphan"
      functions. These activities impact a wide range of biological phenomena including
      metabolism, RNA modification, nuclear morphology, and mitochondrial function.
      Here, we review the discovery and characterization of orphan lysine
      acetyltransferase functions. In addition to highlighting the evidence and
      biological role for these functions in human disease, we discuss the part
      emerging chemical tools may play in investigating this versatile enzyme
      superfamily. 

PMID- 25591749
TI  - Postmortem MR quantification of the heart for characterization and
      differentiation of ischaemic myocardial lesions.
AB  - OBJECTIVES: Recently, an MRI quantification sequence has been developed which can
      be used to acquire T1- and T2-relaxation times as well as proton density (PD)
      values. Those three quantitative values can be used to describe soft tissue in an
      objective manner. The purpose of this study was to investigate the applicability
      of quantitative cardiac MRI for characterization and differentiation of ischaemic
      myocardial lesions of different age. MATERIALS AND METHODS: Fifty post-mortem
      short axis cardiac 3 T MR examinations have been quantified using a
      quantification sequence. Myocardial lesions were identified according to
      histology and appearance in MRI images. Ischaemic lesions were assessed for mean
      T1-, T2- and proton density values. Quantitative values were plotted in a 3D
      coordinate system to investigate the clustering of ischaemic myocardial lesions.
      RESULTS: A total of 16 myocardial lesions detected in MRI images were
      histologically characterized as acute lesions (n = 8) with perifocal oedema (n =
      8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising
      the combined quantitative values of T1, T2 and PD, the clusters of all
      investigated lesions could be well differentiated from each other. CONCLUSION:
      Post-mortem quantitative cardiac MRI is feasible for characterization and
      discrimination of different age stages of myocardial infarction. KEY POINTS: * MR
      quantification is feasible for characterization of different stages of myocardial
      infarction. * The results provide the base for computer-aided MRI cardiac
      infarction diagnosis. * Diagnostic criteria may also be applied for living
      patients.

PMID- 25591750
TI  - Opportunistic screening for osteoporosis on routine computed tomography? An
      external validation study.
AB  - OBJECTIVES: Opportunistic screening for osteoporosis using computed tomography
      (CT) examinations that happen to visualise the spine can be used to identify
      patients with osteoporosis. We sought to verify the diagnostic performance of
      vertebral Hounsfield unit (HU) measurements on routine CT examinations for
      diagnosing osteoporosis in a separate, external population. METHODS: Consecutive
      patients who underwent a CT examination of the chest or abdomen and had also
      received a dual-energy X-ray absorptiometry (DXA) test were retrospectively
      included. CTs were evaluated for vertebral fractures and vertebral attenuation
      (density) values were measured. Diagnostic performance measures and the area
      under the receiver operator characteristics curve (AUC) for diagnosing
      osteoporosis were calculated. RESULTS: Three hundred and two patients with a mean
      age of 57.9 years were included, of which 82 (27%) had osteoporosis according to
      DXA and 65 (22%) had vertebral fractures. The diagnostic performance for
      vertebral HU measurements was modest, with a maximal AUC of 0.74 (0.68 - 0.80).
      At that optimal threshold the sensitivity was 62% (51 - 72%) and the specificity
      was 79% (74 - 84%). CONCLUSIONS: We confirmed that simple trabecular vertebral
      density measurements on routine CT contain diagnostic information related to bone
      mineral density as measured by DXA, albeit with substantially lower diagnostic
      accuracy than previously reported. KEY POINTS: * We externally validated the
      value of vertebral trabecular bone attenuation for osteoporosis * These
      diagnostic performance measures were, however, substantially lower than
      previously reported * This information might be useful when considering the
      implementation of opportunistic osteoporosis screening.

PMID- 25591751
TI  - Characteristics of aortic valve dysfunction and ascending aorta dimensions
      according to bicuspid aortic valve morphology.
AB  - OBJECTIVE: To characterize aortic valve dysfunction and ascending aorta
      dimensions according to bicuspid aortic valve (BAV) morphology using computed
      tomography (CT) and surgical findings. METHODS: We retrospectively enrolled 209
      patients with BAVs who underwent transthoracic echocardiography (TTE) and CT.
      BAVs were classified as anterior-posterior (BAV-AP) or lateral (BAV-LA)
      orientation of the cusps and divided according to the presence (raphe+) or
      absence (raphe-) of a raphe. Ascending aortic dimensions were measured by CT at
      four levels. RESULTS: BAV-AP was present in 129 patients (61.7%) and raphe+ in
      120 (57.4%). Sixty-nine patients (33.0%) had aortic regurgitation (AR), 70
      (33.5%) had aortic stenosis (AS), and 58 (27.8%) had combined AS and AR. AR was
      more common in patients with BAV-AP and raphe+; AS was more common with BAV-LA
      and raphe-.Annulus/body surface area and tubular portion/body surface area
      diameters in patients with BAV-AP (17.1 +/- 2.3 mm/m(2) and 24.2 +/- 5.3 mm/m(2),
      respectively) and raphe+ (17.3 +/- 2.2 mm/m(2) and 24.2 +/- 5.5 mm/m(2),
      respectively) were significantly different from those with BAV-LA (15.8 +/- 1.9
      mm/m(2) and 26.4 +/- 5.5 mm/m(2), respectively) and raphe- (15.7 +/- 1.9 mm/m(2)
      and 26.2 +/- 5.4 mm/m(2), respectively). CONCLUSION: The morphological
      characteristics of BAV might be associated with the type of valvular dysfunction,
      and degree and location of an ascending aorta dilatation. KEY POINTS: * The BAV
      AP type had more frequent aortic regurgitation, raphe, and a larger aortic
      annulus. * BAV without raphe had more frequent aortic stenosis and mid-ascending
      aorta dilatation. * CT allows assessment of the morphological characteristics of
      BAV and associated aortopathy.

PMID- 25591752
TI  - Single-molecule dataset (SMD): a generalized storage format for raw and processed
      single-molecule data.
AB  - BACKGROUND: Single-molecule techniques have emerged as incisive approaches for
      addressing a wide range of questions arising in contemporary biological research
      [Trends Biochem Sci 38:30-37, 2013; Nat Rev Genet 14:9-22, 2013; Curr Opin Struct
      Biol 2014, 28C:112-121; Annu Rev Biophys 43:19-39, 2014]. The analysis and
      interpretation of raw single-molecule data benefits greatly from the ongoing
      development of sophisticated statistical analysis tools that enable accurate
      inference at the low signal-to-noise ratios frequently associated with these
      measurements. While a number of groups have released analysis toolkits as open
      source software [J Phys Chem B 114:5386-5403, 2010; Biophys J 79:1915-1927, 2000;
      Biophys J 91:1941-1951, 2006; Biophys J 79:1928-1944, 2000; Biophys J 86:4015
      4029, 2004; Biophys J 97:3196-3205, 2009; PLoS One 7:e30024, 2012; BMC
      Bioinformatics 288 11(8):S2, 2010; Biophys J 106:1327-1337, 2014; Proc Int Conf
      Mach Learn 28:361-369, 2013], it remains difficult to compare analysis for
      experiments performed in different labs due to a lack of standardization.
      RESULTS: Here we propose a standardized single-molecule dataset (SMD) file
      format. SMD is designed to accommodate a wide variety of computer programming
      languages, single-molecule techniques, and analysis strategies. To facilitate
      adoption of this format we have made two existing data analysis packages that are
      used for single-molecule analysis compatible with this format. CONCLUSION:
      Adoption of a common, standard data file format for sharing raw single-molecule
      data and analysis outcomes is a critical step for the emerging and powerful
      single-molecule field, which will benefit both sophisticated users and non
      specialists by allowing standardized, transparent, and reproducible analysis
      practices.

PMID- 25591753
TI  - [Cardiac and metabolic risk factors in severe mental disorders. Task of a
      prevention manager].
AB  - People with severe mental disorders have a reduction in life expectancy of 13-30
      % compared with the general population. This severe disadvantage is primarily due
      to an increased prevalence of cardiac and metabolic disorders, especially
      coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of
      untoward health behavior characterized by smoking, low levels of physical
      activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid
      disorders are also associated with this behavior and further increase the risk of
      CHD and type 2 diabetes. Thus, people with mental disorders constitute a
      population with a high risk of cardiovascular events. Appropriate measures for
      prevention and therapy are urgently indicated but rarely applied. This article
      presents new organizational structures to overcome this deficit with a prevention
      manager playing a central role in organizing and applying preventive and
      therapeutic care. Results from cardiology and diabetic medicine have shown the
      effectiveness of pooling this responsibility. The measure has the potential to
      reduce the increased mortality of people with severe mental disorders. 

PMID- 25591754
TI  - Capacitance-modulated transistor detects odorant binding protein chiral
      interactions.
AB  - Peripheral events in olfaction involve odorant binding proteins (OBPs) whose role
      in the recognition of different volatile chemicals is yet unclear. Here we report
      on the sensitive and quantitative measurement of the weak interactions associated
      with neutral enantiomers differentially binding to OBPs immobilized through a
      self-assembled monolayer to the gate of an organic bio-electronic transistor. The
      transduction is remarkably sensitive as the transistor output current is governed
      by the small capacitance of the protein layer undergoing minute changes as the
      ligand-protein complex is formed. Accurate determination of the free-energy
      balances and of the capacitance changes associated with the binding process
      allows derivation of the free-energy components as well as of the occurrence of
      conformational events associated with OBP ligand binding. Capacitance-modulated
      transistors open a new pathway for the study of ultra-weak molecular interactions
      in surface-bound protein-ligand complexes through an approach that combines bio
      chemical and electronic thermodynamic parameters. 

PMID- 25591755
TI  - Renal denervation decreases effective refractory period but not inducibility of
      ventricular fibrillation in a healthy porcine biomodel: a case control study.
AB  - BACKGROUND: Ventricular arrhythmias play an important role in cardiovascular
      mortality especially in patients with impaired cardiac and autonomic function.
      The aim of this experimental study was to determine, if renal denervation (RDN)
      could decrease the inducibility of ventricular fibrillation (VF) in a healthy
      porcine biomodel. METHODS: Controlled electrophysiological study was performed in
      6 biomodels 40 days after RDN (RDN group) and in 6 healthy animals (control
      group). The inducibility of VF was tested by programmed ventricular stimulation
      from the apex of right ventricle (8 basal stimuli coupled with up to 4
      extrastimuli) always three times in each biomodel using peripheral extracorporeal
      oxygenation for hemodynamic support. Further, basal heart rate (HR), PQ and QT
      intervals and effective refractory period of ventricles (ERP) were measured.
      Technical success of RDN was evaluated by histological examination. RESULTS:
      According to histological findings, RDN procedure was successfully performed in
      all biomodels. Comparing the groups, basal HR was lower in RDN group: 79 (IQR 58;
      88) vs. 93 (72; 95) beats per minute (p = 0.003); PQ interval was longer in RDN
      group: 145 (133; 153) vs. 115 (113; 120) ms (p < 0.0001) and QTc intervals were
      comparable: 402 (382; 422) ms in RDN vs. 386 (356; 437) ms in control group (p =
      0.1). ERP was prolonged significantly in RDN group: 159 (150; 169) vs. 140 (133;
      150) ms (p = 0.001), but VF inducibility was the same (18/18 vs. 18/18 attempts).
      CONCLUSIONS: RDN decreased the influence of sympathetic nerve system on the heart
      conduction system in healthy porcine biomodel. However, the electrophysiological
      study was not associated with a decrease of VF inducibility after RDN.

PMID- 25591756
TI  - Midazolam inhibits the apoptosis of astrocytes induced by oxygen glucose
      deprivation via targeting JAK2-STAT3 signaling pathway.
AB  - BACKGROUND: There is an increasing interest in the role of astrocytes
      contributing to the intrinsic bioremediation of ischemic brain injury. The
      purpose of this study was to disclose the effects and mechanism of midazolam
      (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose
      deprivation (OGD) condition. METHODS: The astrocytes were assigned randomly into
      four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The
      astrocytes were treated with MDZ at dose of 10 MUmol/L in OGD+MDZ group. And in
      OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10 MUmol/L
      and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation,
      and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry.
      Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and
      Caspase-3 proteins were determined by western blotting assay. RESULTS: Astrocytes
      proliferation was decreased obviously in OGD group, while MDZ could increase
      astrocytes proliferation under OGD condition. Moreover, OGD could induce
      apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6,
      a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects
      of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group
      increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3
      proteins decreased relative to OGD group. But IL-6 could counteract the anti
      apoptotic effects of MDZ. CONCLUSION: Midazolam has protective effects on the
      proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro.
      We firstly disclose the beneficial roles of midazolam in astrocytes under
      ischemic condition, which may be a rational treatment selection for ischemic
      cerebral protection.

PMID- 25591757
TI  - Increased levels of type 1 interferon in a type 1 diabetic mouse model induce the
      elimination of B cells from the periphery by apoptosis and increase their
      retention in the spleen.
AB  - BACKGROUND: The autoimmune disease type 1 diabetes mellitus (T1D) is associated
      with a defect in the immune response, which increases susceptibility to
      infection. We recently demonstrated that prolonged elevated levels of type 1
      interferon (IFN) induce lymphocyte exhaustion during T1D. AIMS: In the present
      study, we further investigated the effect of blocking the type I IFN receptor
      signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile
      leads to the exhaustion of B cells and alteration of their distribution and
      functions. METHODS: T1D was induced in a mouse model by an intraperitoneal
      injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of
      mice were examined: a non-diabetic control group, a diabetic group and a diabetic
      group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1)
      blocking antibody to block type I IFN signaling. RESULTS: We observed that
      induction of T1D was accompanied by a marked destruction of beta cells and a
      reduction in the insulin levels in the diabetic group. Diabetic mice exhibited
      many changes, including alterations in their lipid profiles, expansion of splenic
      B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B
      cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the
      insulin and lipid profiles to normal levels, subsequently restored the B cell
      distribution, and rescued the peripheral B cells from apoptosis. CONCLUSION: Our
      data suggest the potential role of type I IFN in mediating diabetic dyslipidemia
      and an exhausted state of B cells during T1D.

PMID- 25591758
TI  - Influence of N- acetylcysteine on oxidative stress in slow-twitch soleus muscle
      of heart failure rats.
AB  - BACKGROUND: Chronic heart failure is characterized by decreased exercise capacity
      with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle
      abnormalities can play a role in exercise intolerance. Causal or contributing
      factors responsible for muscle alterations have not been completely defined. This
      study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in
      rats with myocardial infarction (MI) induced heart failure. METHODS AND RESULTS:
      Four months after MI, rats were assigned to Sham, MI-C (without treatment), and
      MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram
      showed left ventricular dysfunction in MI-C; NAC attenuated diastolic
      dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase
      activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar
      in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species
      (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation
      fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ
      between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher
      in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in
      Sham and MI-C and lower in MI-NAC. Gene expression of p47(phox) was lower in MI-C
      than Sham. NAC decreased NOX4 and p22(phox) expression. CONCLUSIONS: We
      corroborate the case that oxidative stress is increased in skeletal muscle of
      heart failure rats and show for the first time that oxidative stress is not
      related to increased NADPH oxidase activity.

PMID- 25591759
TI  - Inflammatory cytokine TSLP stimulates platelet secretion and potentiates platelet
      aggregation via a TSLPR-dependent PI3K/Akt signaling pathway.
AB  - AIMS: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory
      diseases and is over-expressed in human atherosclerotic artery specimens. The
      present study investigated the role of TSLP in platelet activation and thrombosis
      models in vitro and in vivo, as well as the underlying mechanism and signaling
      pathway. METHODS AND RESULTS: Western blotting and flow cytometry demonstrated
      that the TSLP receptor was expressed on murine platelets. According to flow
      cytometry, platelet stimulation with TSLP induced platelet degranulation and
      integrin alphaIIbbeta3 activation. A TSLPR deficiency caused defective platelet
      aggregation, defective platelet secretion and markedly blunted thrombus growth in
      perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited
      defective carotid artery thrombus formation after exposure to FeCl3. TSLP
      increased Akt phosphorylation, an effect that was abrogated by the PI3K
      inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP
      induced platelet activation. TSLP-mediated platelet degranulation, integrin
      alphaIIbbeta3 activation and Akt phosphorylation were blunted in platelets that
      lacked the TSLP receptor. CONCLUSION: This study demonstrated that the functional
      TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP
      triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt
      signaling, which suggests an important role for TSLP in linking vascular
      inflammation and thrombo-occlusive diseases.

PMID- 25591760
TI  - The OPN gene polymorphism confers the susceptibility and response to Ara-C based
      chemotherapy in Chinese AML patients.
AB  - AIM: To investigate the possible association between the Osteopontin (OPN) gene
      polymorphisms and the susceptibility and chemotherapy response of acute myeloid
      leukemia patients. METHODS: A total of 381 patients with de nova AML and 430
      healthy controls were enrolled. All patients received Ara-C-based standard
      induction chemotherapy regimens, and the treatment response was evaluated.
      Several polymorphisms in the human OPN encoding gene have been identified. The
      OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were
      determined. RESULTS: We identified that the -443C>T polymorphism was the only one
      which is closely related to AML. Compared with the -443TT carriers, our data
      showed that the -443CC genotype carriers were significantly related to a higher
      risk for AML. The -443CC genotype was also more prevalent in poor response groups
      than in good response group. The -443CC carriers are more likely to have poor
      response to AML treatment. Cellular assay indicated that the leukemic cell lines
      receiving the OPN -443C transfection have a significantly lower apoptosis rate to
      Ara-C treatment compared to cell lines transfected with -443T. CONCLUSION: The
      findings of this study suggest OPN-443C>T gene polymorphism may be sued as a
      molecular for susceptibility and chemotherapy response of AML.

PMID- 25591761
TI  - Modulation of FoxO1 expression by miR-21 to promote growth of pancreatic ductal
      adenocarcinoma.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal
      primary tumors in humans, with undetermined tumorigenesis. Although previous work
      by us, and by others, has clearly demonstrated an involvement of miR-21 in the
      growth of PDAC, the underlying mechanism has not been clarified. METHODS: Here we
      analyzed the regulation of FoxO1 by miR-21 in vitro and in vivo, using luciferase
      reporter assay and pancreatic intraductal infusion of antisense of miR-21,
      respectively. RESULTS: We found that overexpression of miR-21 in PDAC cells
      decreased FoxO1 protein levels, whereas inhibition of miR-21 increased FoxO1
      levels. Further, miR-21 bound to FoxO1 mRNA to prevent its translation through
      its 3'UTR. Moreover, administration of antisense of miR-21 through an intraductal
      infusion system significantly decreased miR-21 levels and increased FoxO1 levels
      in implanted PDAC, resulting in a significant decrease in PDAC growth.
      CONCLUSION: Taken together, our data highlight miR-21/FoxO1 axis as a novel
      therapeutic target for inhibiting the growth of PDAC.

PMID- 25591762
TI  - AMP-activated protein kinase alleviates extracellular matrix accumulation in high
      glucose-induced renal fibroblasts through mTOR signaling pathway.
AB  - BACKGROUND/AIMS: Extracellular matrix accumulation contributes significantly to
      the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase
      (AMPK) has been found to inhibit extracellular matrix synthesis by experiments in
      vivo and vitro, its role in alleviating the deposition of extracellular matrix in
      renal interstitial fibroblasts has not been well defined. METHODS: Currently, we
      conducted this study to investigate the effects of AMPK on high glucose-induced
      extracellular matrix synthesis and involved intracellular signaling pathway by
      using western blot in the kidney fibroblast cell line (NRK-49f). RESULTS:
      Collagen IV protein levels were significantly increased by high glucose in a time
      dependent manner. This was associated with a decrease in Thr72 phosphorylation of
      AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced
      extracellular matrix accumulation and mTOR activation were significantly
      inhibited by the co-treatment of rAAV-AMPKalpha1(312) (encoding constitutively
      active AMPKalpha1) whereas activated by r-AAV-AMPKalpha1D157A (encoding dominant
      negative AMPKalpha1). In cultured renal fibroblasts, overexpression of
      AMPKalpha1D157A upregulated mTOR signaling and matrix synthesis, which were
      ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. CONCLUSION:
      Collectively, these findings indicate that AMPK exerts renoprotective effects by
      inhibiting the accumulation of extracellular matrix through mTOR signaling
      pathway.

PMID- 25591763
TI  - Des-gamma-carboxy prothrombin (DCP) antagonizes the effects of gefitinib on human
      hepatocellular carcinoma cells.
AB  - BACKGROUND/AIMS: Des-gamma-carboxy prothrombin (DCP), an aberrant prothrombin
      produced by hepatocellular carcinoma (HCC) cells, is known as a marker for HCC.
      Recent studies indicated that high levels of DCP are associated with the
      malignant potential of HCC. In this study, we aimed to investigate the
      association of DCP with gefitinib treatment failure in HCC and whether DCP
      counteracts gefitinib-induced growth inhibition and apoptosis of HCC. METHODS:
      The experiments were performed in HCC cell lines HepG2 and PLC/PRF/5. The effects
      of gefitinib on HCC in the presence or absence of DCP were evaluated by the 3-[4,
      5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptotic
      cells were identified by Annexin V-FITC/PI staining. Western blotting was
      performed to analyze the expressions of molecules related to the apoptotic
      caspase-dependent pathway and epidermal growth factor receptor (EGFR) pathway.
      RESULTS: Gefitinib inhibited HCC cell proliferation and induced apoptosis in HCC
      cells. The effects of gefitinib on HCC cells were antagonized by DCP. In the
      presence of DCP, HCC cells were resistant to the gefitinib-induced inhibition of
      proliferation and stimulation of apoptosis. DCP prevented the activation of the
      apoptotic caspase-dependent pathway induced by gefitinib. These antagonistic
      effects of DCP also arose from its ability to up-regulate EGFR, c-Met and
      hepatocyte growth factor (HGF) in HCC cells. CONCLUSION: DCP antagonized
      gefitinib-induced HCC cell growth inhibition by counteracting apoptosis and up
      regulating the EGFR pathway. High levels of DCP might thus lead to low response
      rates or possibly no response to gefitinib in patients with HCC.

PMID- 25591764
TI  - MicroRNA-101a inhibits cardiac fibrosis induced by hypoxia via targeting
      TGFbetaRI on cardiac fibroblasts.
AB  - BACKGROUND/AIMS: Hypoxia is a basic pathological challenge that is associated
      with numerous cardiovascular disorders including aberrant cardiac remodeling.
      Transforming growth factor beta (TGF-beta) signaling pathway plays a pivotal role
      in mediating cardiac fibroblast (CF) function and cardiac fibrosis. Recent data
      suggested that microRNA-101a (miR-101a) exerted anti-fibrotic effects in post
      infarct cardiac remodeling and improved cardiac function. This study aimed to
      investigate the potential relationship between hypoxia, miR-101a and TGF-beta
      signaling pathway in CFs. METHODS AND RESULTS: Two weeks following coronary
      artery occlusion in rats, the expression levels of both TGFbeta1 and TGFbetaRI
      were increased, but the expression of miR-101a was decreased at the site of the
      infarct and along its border. Cultured rat neonatal CFs treated with hypoxia were
      characterized by the up-regulation of TGFbeta1 and TGFbetaRI and the down
      regulation of miR-101a. Delivery of miR-101a mimics significantly suppressed the
      expression of TGFbetaRI and p-Smad 3, CF differentiation and collagen content of
      CFs. These anti-fibrotic effects were abrogated by co-transfection with AMO-miR
      101a, an antisense inhibitor of miR-101a. The repression of TGFbetaRI, a target
      of miR-101a, was validated by luciferase reporter assays targeting the 3'UTR of
      TGFbetaRI. Additionally, we found that overexpression of miR-101a reversed the
      improved migration ability of CFs and further reduced CF proliferation caused by
      hypoxia. CONCLUSION: Our study illustrates that miR-101a exerts anti-fibrotic
      effects by targeting TGFbetaRI, suggesting that miR-101a plays a multi-faceted
      role in modulating TGF-beta signaling pathway and cardiac fibrosis.

PMID- 25591765
TI  - MiR-301a promotes colorectal cancer cell growth and invasion by directly
      targeting SOCS6.
AB  - BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most common malignancies
      worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this
      study was to investigate the exact functions and potential mechanisms of action
      of miR-301a in CRC. METHODS: Quantitative real-time PCR was conducted to assess
      the expression of miR-301a. Cell proliferation was detected using MTT and colony
      formation assay, and cell invasion and migration were evaluated using Transwell
      assay. Luciferase reporter assay was used to identify the direct regulation of
      suppressor of cytokine signaling 6 (SOCS6) by miR-301a. RESULTS: We first
      confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of
      function and loss-of-function studies in the human CRC cell lines, SW480 and
      SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation,
      migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified
      as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR
      301a-induced cell proliferation, migration and invasion. CONCLUSION: These data
      suggest that miR-301a promotes CRC progression by directly downregulating SOCS6
      expression, and miR-301a may represent a novel biomarker for the prevention and
      treatment of CRC.

PMID- 25591766
TI  - RNF125 is a ubiquitin-protein ligase that promotes p53 degradation.
AB  - BACKGROUND/AIMS: Although early studies show that Mdm2 is the primary E3
      ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data
      suggests that p53 ubiquitination and degradation are more complex than once
      thought. Here, we investigated the role of RNF125, a non-Mdm2 ubiquitin-protein
      ligase, in the regulation of p53. METHODS AND RESULTS: RNF125 physically
      interacted with p53 in exogenous/endogenous co-immunoprecipitation (IP) and GST
      pull down assay, and a C72/75A mutation of RNF125 did not interfere with this
      interaction. Expression of RNF125 decreased the level of p53 in a dose-dependent
      manner, whereas knockdown of RNF125 by RNA interference increased the level of
      p53. As shown by Western blotting and ubiquitin assay, RNF125 ubiquitinated p53
      and targeted it for proteasome degradation. Furthermore, RNF125 repressed p53
      functions including p53-dependent transactivation and growth inhibition.
      CONCLUSION: Our data suggest that RNF125 negatively regulates p53 function
      through physical interaction and ubiquitin-mediated proteasome degradation.

PMID- 25591767
TI  - MiR-133b Promotes neurite outgrowth by targeting RhoA expression.
AB  - BACKGROUND: MicroRNA-133b (miR-133b) has been shown to play a critical role in
      spinal cord regeneration. The aim of this study was to investigate the cellular
      role of miR-133b in neural cells. METHODS: PC12 cells and primary cortical
      neurons (PCNs) were transfected with lenti-miR-133b, lenti-miR-133b inhibitor,
      plasmid-shRNA-RhoA, plasmid-RhoA and their negative controls. After 48 hours of
      transfection, the levels of proteins and mRNA or miRNA were evaluated by Western
      blotting and qRT-PCR, respectively. Moreover, the neurite outgrowth was analyzed
      by Image J. For pharmacological experiments, inhibitors of MEK1/2 kinase
      (PD98059), phosphoinositide-3 kinase (PI3K) (LY294002) and ROCK (Y27632) were
      added into the culture medium. RESULTS: Overexpression of miR-133b in PC12 cells
      enhanced neurite outgrowth. Conversely, inhibition of miR-133b reduced neurite
      length. We further identified RhoA as a target and mediator of mir-133b for
      neurite extension by Western blot and knockdown experiment. Moreover,
      overexpression of RhoA could attenuate the neurite growth effects of miR-133b.
      Also, we observed that miR-133b activated MEK/ERK and PI3K/Akt signaling pathway
      by targeting RhoA. Finally, in PCNs, miR-133b also increased axon growth and
      attenuated axon growth restrictions from chondroitin sulfate proteoglycans
      (CSPG). CONCLUSIONS: In summary, our study suggested that miR-133b regulated
      neurite outgrowth via ERK1/2 and PI3K/Akt signaling pathway by RhoA suppression.

PMID- 25591769
TI  - Patients carrying 9q31.1-q32 deletion share common features with Cornelia de
      Lange Syndrome.
AB  - BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a rare but severe clinically
      heterogeneous developmental disorder characterized by facial dysmorphia, growth
      and cognitive retardation, and abnormalities of limb development. OBJECTIVES: To
      determine the pathogenesis of a patient with CdLS. METHODS: We studied a patient
      with CdLS by whole exome sequencing, karyotyping and Agilent CGH Array. The
      results were confirmed by quantitative real-time PCR analysis of the patient and
      her parents. Further comparison of our patient and cases with partially
      overlapping deletions retrieved from the literature and databases was undertaken.
      RESULTS: Whole exome sequencing had excluded the mutation of cohesion genes such
      as NIPBL,SMC1A and SMC3. The result of karyotyping showed a deletion of
      chromosome 9q31.1-q32 and the result of Agilent CGH Array further displayed a
      12.01-Mb region of deletion at chromosome bands 9q31.1-q32. Reported cases with
      the deletion of 9q31.1-q32 share similar features with our CdLS patient. One of
      the genes in the deleted region, SMC2, belongs to the Structural Maintenance of
      Chromosomes (SMC) family and regulates gene expression and DNA repair.
      CONCLUSIONS: Patients carrying the deletion of 9q31.1-q32 showed similar
      phenotypes with CdLS.

PMID- 25591768
TI  - Pamidronate attenuates diastolic dysfunction induced by myocardial infarction
      associated with changes in geometric patterning.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the influence of
      pamidronate on ventricular remodeling after myocardial infarction. METHODS: Male
      Wistar rats were assigned to four groups: a sham group, in which animals were
      submitted to simulated surgery and received weekly subcutaneous injection of
      saline (S group; n=14); a group in which animals received weekly subcutaneous
      injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated
      surgery (SP group, n=14); a myocardial infarction group, in which animals were
      submitted to coronary artery ligation and received weekly subcutaneous injection
      of saline (MI group, n=13); and a myocardial infarction group with pamidronate
      treatment (MIP group, n=14). The rats were observed for three months. RESULTS:
      Animals submitted to MI had left chamber enlargement and worse diastolic and
      systolic function compared with SHAM groups. E/A ratio, LV posterior and relative
      wall thickness were lower in the MIP compared with the MI group. There was no
      interaction between pamidronate administration and MI on systolic function,
      myocyte hypertrophy, collagen content, and calcium handling proteins. CONCLUSION:
      Pamidronate attenuates diastolic dysfunction following MI.

PMID- 25591770
TI  - Genetic association of MiR-146a with multiple sclerosis susceptibility in the
      Chinese population.
AB  - BACKGROUND: miR-146a polymorphisms have been involved in susceptibility to
      multiple diseases. The aim of the present study was to analyze the potential
      association between two functional miR-146a polymorphisms (rs2910164 and
      rs57095329) and multiple sclerosis (MS) in the Han Chinese population. METHODS: A
      cohort of 525 patients and 568 healthy controls were genotyped to detect the two
      polymorphisms by SNaPshot. RESULTS: No significant differences were detected in
      the distribution of the two miR-146a polymorphisms between the patients and
      controls (P > 0.05). However, stratification by gender showed a statistically
      significant difference in the frequency of the genotype rs2910164 between MS
      patients and control females (P=0.009). Further stratification analysis by
      subgroup revealed that the miR-146a rs2910164 C allele conferred a higher risk of
      developing relapsing-remitting MS (RRMS) (P=0.018). In addition, the rs2910164 C
      allele was significantly associated with increased expression of miR-146a in
      patients with RRMS (P=0.025). Moreover, patients with the rs2910164 C allele
      released more TNF-alpha and IFN-gamma, but not IL-1beta, compared with
      individuals carrying the homozygous GG genotype (P < 0.05). CONCLUSIONS: Our
      results provide evidence that rs2910164 may play a role in MS susceptibility in
      females. The rs2910164 G>C variation may affect the expression of miR-146a and
      the release of proinflammatory cytokines.

PMID- 25591771
TI  - Expansion of myeloid-derived suppressor cells in patients with acute coronary
      syndrome.
AB  - AIM: The aim of this study was to explore whether the circulating frequency and
      function of myeloid-derived suppressor cells (MDSCs) are altered in patients with
      acute coronary syndrome (ACS). METHODS: The frequency of MDSCs in peripheral
      blood was determined by flow cytometry, and mRNA expression in purified MDSCs was
      analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR).
      The suppressive function of MDSCs isolated from different groups was also
      determined. The plasma levels of certain cytokines were determined using Bio-Plex
      ProTM Human Cytokine Assays. RESULTS: The frequency of circulating CD14(+)HLA-DR(
      /low) MDSCs; arginase-1 (Arg-1) expression; and plasma levels of interleukin (IL)
      1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-33 were markedly increased
      in ACS patients compared to stable angina (SA) or control patients. Furthermore,
      MDSCs from ACS patients were more potent suppressors of T-cell proliferation and
      IFN-gamma production than those from the SA or control groups at ratios of 1:4
      and 1:2; this effect was partially mediated by Arg-1. In addition, the frequency
      of MDSCs was positively correlated with plasma levels of IL-6, IL-33, and TNF
      alpha. CONCLUSIONS: We observed an increased frequency and suppressive function
      of MDSCs in ACS patients, a result that may provide insights into the mechanisms
      involved in ACS.

PMID- 25591772
TI  - Electrophysiological characteristics of embryonic stem cell-derived
      cardiomyocytes are cell line-dependent.
AB  - BACKGROUND: Modelling of cardiac development, physiology and pharmacology by
      differentiation of embryonic stem cells (ESCs) requires comparability of cardiac
      differentiation between different ESC lines. To investigate whether the outcome
      of cardiac differentiation is consistent between different ESC lines, we compared
      electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs) of
      different murine ESC lines. METHODS: Two wild-type (D3 and R1) and two transgenic
      ESC lines (D3/aPIG44 and CGR8/AMPIGX-7) were differentiated under identical
      culture conditions. The transgenic cell lines expressed enhanced green
      fluorescent protein (eGFP) and puromycin-N-acetyltransferase under control of the
      cardiac specific alpha-myosin heavy chain (alphaMHC) promoter. Action potentials
      (APs) were recorded using sharp electrodes and multielectrode arrays in beating
      clusters of ESC-CMs. RESULTS: Spontaneous AP frequency and AP duration (APD) as
      well as maximal upstroke velocity differed markedly between unpurified CMs of the
      four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and
      R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term
      recordings showed a high degree of variability within and between recordings in
      CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the alphaMHC+ population by
      puromycin treatment posed only minor changes to APD in D3/aPIG44, but
      significantly shortened APD in CGR8/AMPIGX-7. CONCLUSION: Electrophysiological
      properties of ESC-CMs are strongly cell line-dependent and can be influenced by
      purification of cardiomyocytes by antibiotic selection. Thus, conclusions on
      cardiac development, physiology and pharmacology derived from single stem cell
      lines have to be interpreted carefully.

PMID- 25591773
TI  - Ketamine interferes with the proliferation and differentiation of neural stem
      cells in the subventricular zone of neonatal rats.
AB  - BACKGROUND: Previous studies have shown ketamine can alter the proliferation and
      differentiation of neural stem cells (NSCs) in vitro. However, these effects have
      not been entirely clarified in vivo in the subventricular zone (SVZ) of neonatal
      rats. The present study was designed to investigate the effects of ketamine on
      the proliferation and differentiation of NSCs in the SVZ of neonatal rats in
      vivo. METHODS: Postnatal day 7 (PND-7) male Sprague-Dawley rats were administered
      four injections of 40 mg/kg ketamine at 1-h intervals, and then 5
      bromodeoxyuridine (BrdU) was injected intraperitoneally at PND-7, 9 and 13. NSC
      proliferation was assessed with Nestin/BrdU double-labeling immunostaining.
      Neuronal and astrocytic differentiation was evaluated with beta-tubulin III/BrdU
      and GFAP/BrdU double-labeling immunostaining, respectively. The expressions of
      nestin, beta-tubulin III and GFAP were measured using Western blot analysis. The
      apoptosis of NSCs and astrocytes in the SVZ of neonatal rats was evaluated using
      nestin/caspase-3 and GFAP/caspase-3 double-labeling immunostaining. RESULTS:
      Neonatal ketamine exposure significantly reduced the number of nestin/BrdU and
      GFAP/BrdU double-positive cells in the SVZ. Meanwhile, the expressions of nestin
      and GFAP in the SVZ from the ketamine group were significantly decreased compared
      those in the control group. Still, no double-positive cells for nestin/caspase-3
      and GFAP/caspase-3 were found after ketamine exposure. In addition, the neuronal
      differentiation of NSCs in the SVZ was markedly promoted by ketamine with an
      increased number of beta-tubulin III/BrdU double-positive cells and enhanced
      expression of beta-tubulin III. These effects of ketamine on the NSCs in the SVZ
      often lasted at least 1 week after ketamine anesthesia. CONCLUSION: In the
      present study, it was demonstrated that ketamine could alter neurogenesis by
      inhibiting the proliferation of NSCs, suppressing their differentiation into
      astrocytes and promoting the neuronal differentiation of the NSCs in the SVZ of
      neonatal rats during a critical period of their neurodevelopment.

PMID- 25591774
TI  - Ezrin/Exocyst complex regulates mucin 5AC secretion induced by neutrophil
      elastase in human airway epithelial cells.
AB  - BACKGROUND/AIM: Increased mucin secretion is a characteristic feature of many
      chronic airway diseases, particularly during periods of exacerbation; however,
      the exact mechanism of mucin secretion remains unclear. Ezrin, which is a
      specific marker of apical membranes, is predominantly concentrated in exocyst
      rich cell surface structures, crosslinking the actin cytoskeleton with the plasma
      membrane. In the present study, we examined whether Ezrin is involved in mucin
      5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated
      the role of the exocyst complex docking protein Sec3 in this process. METHODS: NE
      was used as a stimulator in a 16HBE14o- cell culture model. The expression and
      location of Ezrin and Sec3 were investigated, and the interaction between Ezrin
      and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3
      siRNA, neomycin or PIP2-Ab. RESULTS: We found that Ezrin was highly expressed in
      the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC
      protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to
      impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily
      to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab
      treatments abrogated this effect. Immunoprecipitation analysis revealed that
      Ezrin and Sec3 combined to form complexes; however, these complexes could not be
      detected in Ezrin?1-333 mutant-transfected cells, even when PIP2 was added.
      CONCLUSIONS: These results demonstrate that Ezrin/Sec3 complexes are essential
      for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of
      critical importance in the formation of these complexes.

PMID- 25591775
TI  - Knockdown of polycomb-group RING finger 6 modulates mouse male germ cell
      differentiation in vitro.
AB  - BACKGROUND: Polycomb-group RING finger 6 (PCGF6), one of six PCGF homologs, is
      the core component of the PRC1 complex that plays critical roles in epigenetic
      transcriptional silencing in higher eukaryotes. However, the biological functions
      of PCGF6 are unknown. METHOD: qRT-PCR and Western blot were used to detect the
      expression profile of PCGF6 in testes. Fluorescent immunohistochemistry was used
      to examine the cellular localization of PCGF6 protein in testes. Cell
      proliferation was tested by performing CCK-8 and EdU incorporation assay. Cell
      cycle and haploid cell population analysis was determined by flow cytometry using
      propidium iodide DNA staining. Co-immunoprecipitation experiment was conducted
      using PCGF6 antibody to obtain interacting protein of PCGF6. Luciferase reporter
      assays were performed to examine the promoter activity of PCGF6 in cells
      overexpressing OVOL1 and PLZF. RESULTS: PCGF6 was expressed predominantly in
      meiotic and post-meiotic male germ cells, could negatively regulate the
      proliferation of GC-2 spd cells, an immortalized mouse spermatogenic cell line,
      and could modulate the differentiation of GC-2 spd cells in vitro. PCGF6 could
      indirectly interact with HSPA2, a key factor that is essential for male meiosis,
      and OVOL1 and PLZF, two key transcription factors that are involved in
      spermatogenesis, could positively and negatively modulate Pcgf6 promoter
      activity, respectively. PCGF1, BMI1, and PCGF5 are also highly expressed in mouse
      testes like PCGF6. CONCLUSION: PCGF6 may play important roles in male germ cell
      development.

PMID- 25591776
TI  - Ambient fine particulate matter induces apoptosis of endothelial progenitor cells
      through reactive oxygen species formation.
AB  - BACKGROUND/AIMS: Bone marrow (BM)-derived endothelial progenitor cells (EPCs)
      play a critical role in angiogenesis and vascular repair. Some environmental
      insults, like fine particulate matter (PM) exposure, significantly impair
      cardiovascular functions. However, the mechanisms for PM-induced adverse effects
      on cardiovascular system remain largely unknown. The present research was to
      study the detrimental effects of PM on EPCs and explore the potential mechanisms.
      METHODS: PM was intranasal-distilled into male C57BL/6 mice for one month. Flow
      cytometry was used to measure the number of EPCs, apoptosis level of circulating
      EPCs and intracellular reactive oxygen species (ROS) formation. Serum TNF-alpha
      and IL-1beta were measured using ELISA. To determine the role of PM-induced ROS
      in EPC apoptosis, PM was co-administrated with the antioxidant N-acetylcysteine
      (NAC) in wild type mice or used in a triple transgenic mouse line (TG) with
      overexpression of antioxidant enzyme network (AON) composed of superoxide
      dismutase (SOD)1, SOD3, and glutathione peroxidase (Gpx-1) with decreased in vivo
      ROS production. RESULTS: PM treatment significantly decreased circulating EPC
      population, promoted apoptosis of EPCs in association with increased ROS
      production and serum TNF-alpha and IL-1beta levels, which could be effectively
      reversed by either NAC treatment or overexpression of AON. CONCLUSION: PM
      exposure significantly decreased circulating EPCs population due to increased
      apoptosis via ROS formation in mice.

PMID- 25591778
TI  - Matrine inhibits mouse sperm function by reducing sperm [Ca2+]i and phospho
      ERK1/2.
AB  - BACKGROUND: Matrine is a bioactive alkaloid that has a variety of pharmacological
      effects and is widely used in Chinese medicine. However, its effects on male
      reproduction are not well known. In this study, we aimed to investigate the in
      vitro toxicity of matrine on mature mouse sperm. METHODS: Mouse cauda epididymal
      sperm were exposed to matrine (10-200 uM) in vitro. The viability, motility,
      capacitation, acrosome reaction and fertilization ability of the mouse sperm were
      examined. Furthermore, the intracellular calcium concentration ([Ca(2+)]i),
      calcium (Catsper) and potassium (Ksper) currents, and phosphorylation of
      extracellular signal regulated kinases 1/2 (p-ERK1/2) of the sperm were analyzed.
      RESULTS: After exposure to 100 uM or more of matrine, mouse cauda epididymal
      sperm exhibited a significant reduction in total motility, progressive motility,
      linear velocity and acrosome reaction rate induced by Ca(2+) ionophore A23187. As
      a result, the fertilization ability of mouse sperm was remarkably decreased by
      matrine. Our data further demonstrated that matrine significantly reduced sperm
      [Ca(2+)]i and [Ca(2+)]i-related p-ERK1/2; however, both the CatSper and KSper
      currents, which are thought to interactively regulate Ca(2+) influx in sperm,
      were not affected by matrine. CONCLUSION: Our findings indicate that matrine
      inhibits mouse sperm function by reducing sperm [Ca(2+)]i and suppressing the
      phosphorylation of ERK1/2.

PMID- 25591777
TI  - Hyperketonemia (acetoacetate) upregulates NADPH oxidase 4 and elevates oxidative
      stress, ICAM-1, and monocyte adhesivity in endothelial cells.
AB  - BACKGROUND/AIMS: The incidence of developing microvascular dysfunction is
      significantly higher in type 1 diabetic (T1D) patients. Hyperketonemia
      (acetoacetate, beta-hydroxybutyrate) is frequently found along with hyperglycemia
      in T1D. Whether hyperketonemia per se contributes to the excess oxidative stress
      and cellular injury observed in T1D is not known. METHODS: HUVEC were treated
      with ketones in the presence or absence of high glucose for 24 h. NOX4 siRNA was
      used to specifically knockdown NOX4 expression in HUVEC. RESULTS: Ketones alone
      or in combination with high glucose treatment cause a significant increase in
      oxidative stress, ICAM-1, and monocyte adhesivity to HUVEC. Using an antisense
      approach, we show that ketone induced increases in ROS, ICAM-1 expression, and
      monocyte adhesion in endothelial cells were prevented in NOX4 knockdown cells.
      CONCLUSION: This study reports that elevated levels of ketones upregulate NOX,
      contributing to increased oxidative stress, ICAM-1 levels, and cellular
      dysfunction. This provides a novel biochemical mechanism that elucidates the role
      of hyperketonemia in the excess cellular injury in T1D. New drugs targeting
      inhibition of NOX seems promising in preventing higher risk of complications
      associated with T1D.

PMID- 25591779
TI  - Olopatadine inhibits exocytosis in rat peritoneal mast cells by counteracting
      membrane surface deformation.
AB  - BACKGROUND/AIMS: Besides its anti-allergic properties as a histamine receptor
      antagonist, olopatadine stabilizes mast cells by inhibiting the release of
      chemokines. Since olopatadine bears amphiphilic features and is preferentially
      partitioned into the lipid bilayers of the plasma membrane, it would induce some
      morphological changes in mast cells and thus affect the process of exocytosis.
      METHODS: Employing the standard patch-clamp whole-cell recording technique, we
      examined the effects of olopatadine and other anti-allergic drugs on the membrane
      capacitance (Cm) in rat peritoneal mast cells during exocytosis. Using confocal
      imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined
      their effects on the deformation of the plasma membrane. RESULTS: Low
      concentrations of olopatadine (1 or 10 uM) did not significantly affect the GTP
      gamma-S-induced increase in the Cm. However, 100 uM and 1 mM olopatadine almost
      totally suppressed the increase in the Cm. Additionally, these doses completely
      washed out the trapping of the dye on the cell surface, indicating that
      olopatadine counteracted the membrane surface deformation induced by exocytosis.
      As shown by electron microscopy, olopatadine generated inward membrane bending in
      mast cells. CONCLUSION: This study provides electrophysiological evidence for the
      first time that olopatadine dose-dependently inhibits the process of exocytosis
      in rat peritoneal mast cells. Such mast cell stabilizing properties of
      olopatadine may be attributed to its counteracting effects on the plasma membrane
      deformation in degranulating mast cells.

PMID- 25591780
TI  - Effects of moderate exercise on the biochemical, physiological, morphological and
      functional parameters of the aorta in the presence of estrogen deprivation and
      dyslipidemia: an experimental model.
AB  - BACKGROUND: The estrogen deficiency, abnormal lipid profile, weight gain and a
      sedentary lifestyle are factors associated with the increased prevalence of
      cardiovascular disease in menopausal women. However, physical exercise practice
      reduces some of these risk factors. Moreover, it has been shown that exercise has
      an impact on inflammation, in sympathetic activity and improves endothelial
      function. AIMS: The present study aims to evaluate the effects of moderate
      aerobic training on biochemical, morphological and physiological parameters in
      LDL Knockout mice with estrogen deprivation, evaluating the components of the
      ascending aortic wall. METHODS: The animals were randomly divided into six groups
      (n=5): sedentary control (SC), sedentary control ovariectomized (SCO), trained
      control ovariectomized (TCO), LDL-Knockout sedentary (KS), LDL-Knockout sedentary
      ovariectomized (KOS) and LDL-Knockout trained ovariectomized (KOT). The trained
      groups underwent a protocol of moderate training for 4 weeks on a treadmill with
      speed and progressive load. After training, blood samples were collected for
      biochemical assessments and the aorta was removed for dissection and histological
      morphometry study. In addition, the expression of angiotensin-converting enzyme
      (ACE) and angiotensin II proteins were examined by immunohistochemistry in all
      groups of animals. RESULTS: Changes of expressions of ACE and angiotensin II were
      found when the group was subjected to exercise. The concentrations of cholesterol
      and triglycerides were lower in the groups of animals with estrogen deprivation
      and dyslipidemia. In animals that performed exercises we found significant
      increase (p<0.05) in Vv[lam]; decrease in Vv[col] and CWT, and a tendency for
      decrease both in TS and IMT when compared to the SC groups. The histological
      morphometry findings showed consistency in the results of the aorta study when
      the ovariectomized group underwent the exercise protocol. CONCLUSION: We conclude
      that physical training contributed to reducing vessel rigidity and to
      improvements in vascular compliance, with the increase in volume density of
      elastic lamellae in the estrogen-deprived groups who had normal cholesterol
      levels.

PMID- 25591781
TI  - AMP-activated protein kinase alpha1 regulates cardiac gap junction protein
      connexin 43 and electrical remodeling following pressure overload.
AB  - BACKGROUND/AIMS: Adenosine 5'-monophosphate (AMP)-activated protein kinase (Ampk)
      modulates a wide array of cellular functions and regulates various ion channels
      and transporters. In failing human hearts an increased Ampkalpha1 activity was
      observed. The present study aimed to uncover the impact of Ampkalpha1 on cardiac
      electrical remodeling. METHODS: Gene-targeted mice lacking functional Ampkalpha1
      (Ampkalpha1-/-) and corresponding wild-type mice were exposed to pressure
      overload by "transverse aortic constriction" (TAC). In vivo electrophysiology was
      performed with a single catheter technique, myocardial conduction velocities and
      conduction characteristics investigated in isolated hearts, transcript levels
      quantified by RT-PCR and protein abundance determined by Western blotting.
      Moreover, connexin 43 (Cx43) was expressed in Xenopus oocytes with or without
      coexpression of wild-type or mutant AMPK and Cx43 protein abundance quantified
      utilizing confocal microscopy. RESULTS: TAC treatment increased Ampkalpha1
      protein expression in cardiac tissue from wild-type mice. TAC further increased
      left ventricular conduction inhomogeneity and triggered conduction blocks,
      effects blunted in the Ampkalpha1(-/-) mice. TAC treatment decreased Cx43 protein
      abundance in cardiac tissue, an effect significantly blunted in the Ampkalpha1(-/
      ) mice. TAC treatment did not modify Cx43 mRNA levels but increased
      ubiquitination of Cx43 protein, an effect mitigated by Ampkalpha1 deficiency. As
      shown in Xenopus oocytes, Cx43 cell membrane protein abundance was significantly
      downregulated by wild-type AMPK(WT) and constitutively active AMPK(gammaR70Q),
      but not by catalytically inactive AMPK(alphaK45R). CONCLUSION: Ampkalpha1
      stimulates ubiquitination of the gap junction protein Cx43, thereby contributing
      to gap junction remodeling following pressure overload.

PMID- 25591782
TI  - Sm2, a paralog of the Trichoderma cerato-platanin elicitor Sm1, is also highly
      important for plant protection conferred by the fungal-root interaction of
      Trichoderma with maize.
AB  - BACKGROUND: The proteins Sm1 and Sm2 from the biocontrol fungus Trichoderma
      virens belong to the cerato-platanin protein family. Members of this family are
      small, secreted proteins that are abundantly produced by filamentous fungi with
      all types of life-styles. Some species of the fungal genus Trichoderma are
      considered as biocontrol fungi because they are mycoparasites and are also able
      to directly interact with plants, thereby stimulating plant defense responses. It
      was previously shown that the cerato-platanin protein Sm1 from T. virens - and to
      a lesser extent its homologue Epl1 from Trichoderma atroviride - induce plant
      defense responses. The plant protection potential of other members of the cerato
      platanin protein family in Trichoderma, however, has not yet been investigated.
      RESULTS: In order to analyze the function of the cerato-platanin protein Sm2, sm1
      and sm2 knockout strains were generated and characterized. The effect of the lack
      of Sm1 and Sm2 in T. virens on inducing systemic resistance in maize seedlings,
      challenged with the plant pathogen Cochliobolus heterostrophus, was tested. These
      plant experiments were also performed with T. atroviride epl1 and epl2 knockout
      strains. In our plant-pathogen system T. virens was a more effective plant
      protectant than T. atroviride and the results with both Trichoderma species
      showed concordantly that the level of plant protection was more strongly reduced
      in plants treated with the sm2/epl2 knockout strains than with sm1/epl1 knockout
      strains. CONCLUSIONS: Although the cerato-platanin genes sm1/epl1 are more
      abundantly expressed than sm2/epl2 during fungal growth, Sm2/Epl2 are,
      interestingly, more important than Sm1/Epl1 for the promotion of plant protection
      conferred by Trichoderma in the maize-C. heterostrophus pathosystem.

PMID- 25591784
TI  - Scaling of pneumatic digital logic circuits.
AB  - The scaling of integrated circuits to smaller dimensions is critical for
      achieving increased system complexity and speed. Digital logic circuits composed
      of pneumatic microfluidic components have to this point been limited to a circuit
      density of 2-4 gates cm(-2), constraining the complexity of the digital systems
      that can be achieved. We explored the use of precision machining techniques to
      reduce the size of pneumatic valves and resistors, and to achieve more accurate
      and efficient placement of ports and vias. In this way, we attained an order of
      magnitude increase in circuit density, reaching as high as 36 gates cm(-2). A 12
      bit binary counter circuit composed of 96 gates was realized in an area of 360
      mm(2). The reduction in size also brought an order of magnitude increase in
      speed. The frequency of a 13-stage ring oscillator increased from 2.6 Hz to 22.1
      Hz, and the maximum clock frequency of a binary counter increased from 1/3 Hz to
      6 Hz. 

PMID- 25591783
TI  - Cigarette smoking hinders human periodontal ligament-derived stem cell
      proliferation, migration and differentiation potentials.
AB  - Cigarette smoking contributes to the development of destructive periodontal
      diseases and delays its healing process. Our previous study demonstrated that
      nicotine, a major constituent in the cigarette smoke, inhibits the regenerative
      potentials of human periodontal ligament-derived stem cells (PDLSC) through
      microRNA (miRNA) regulation. In this study, we hypothesized that the delayed
      healing in cigarette smokers is caused by the afflicted regenerative potential of
      smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non
      smokers. In smoker PDLSC, we found significantly reduced proliferation rate and
      retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium
      deposition and acidic polysaccharide staining were reduced after BMP2-induced
      differentiation. In contrast, more lipid deposition was observed in adipogenic
      induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305
      (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were
      significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an
      important role in the deteriorative effects on stem cells by cigarette smoke.
      Results of this study provide further evidences that cigarette smoking affects
      the regenerative potentials of human adult stem cells. 

PMID- 25591787
TI  - Exploring the possibilities of two-dimensional transition metal carbides as anode
      materials for sodium batteries.
AB  - Recently a group of two-dimensional materials called MXenes have been discovered
      and they have demonstrated their potential in Li rechargeable batteries. Herein,
      the Na storage and ion migration properties of M2C-type MXenes (M = Ti, V, Cr,
      Mn, Fe, Co, Ni, Nb, Mo) were investigated using density functional theory (DFT)
      calculations, and were compared to the Li case. Based on the average voltage and
      migration barrier of surface ions, we suggest that M = Ti, V, Cr, Mn, and Mo are
      suitable for sodium ion battery (SIB) anodes. These screened M2C materials can
      provide a theoretical capacity of 190-288 mA h g(-1) by accommodating two alkali
      ions per formula unit. They also exhibit an activation barrier of 0.1-0.2 eV for
      ionic motion, suggesting that the M2C materials are promising for high-power
      applications. The underlying aspects of the voltage differences between M2C
      materials are also discussed using electrostatic considerations. 

PMID- 25591786
TI  - Multiparametric magnetic resonance imaging/transrectal ultrasound fusion targeted
      biopsy of the prostate: preliminary results of a prospective single-centre study.
AB  - PURPOSE: To evaluate multiparametric magnetic resonance imaging/transrectal
      ultrasound (mpMRI/TRUS) fusion targeted biopsy (TB) of the prostate for prostate
      cancer (PCa) diagnosis. PATIENTS AND METHODS: From April 2013 to January 2014, 53
      men were included in this prospective single-centre study. The degree of PCa
      suspicion from mpMRI findings was classified according to the PI-RADS scoring
      system. Of these, 50 patients underwent both an mpMRI/TRUS fusion TB and a 10
      core systematic biopsy (SB) of the prostate and were eligible for analysis.
      RESULTS: 225 targeted and 500 systematic cores were included in this study. PCa
      was histologically confirmed in 52.0% of patients (26/50), whereas TB revealed
      PCa in 46.0% (23/50) and SB in 36.0% (18/50). TB identified PCa in 16.0% of all
      patients (8/50) that were missed by SB. All told, the targeted core was 2.8 times
      more likely to be PCa-positive than the systematic core (29.3 vs. 10.4%).
      CONCLUSIONS: mpMRI/TRUS fusion TB of the prostate is safe, practicable and may
      improve PCa diagnosis using fewer biopsy cores compared to SB.

PMID- 25591785
TI  - Intestinal fatty acid binding protein as a marker for intra-abdominal pressure
      related complications in patients admitted to the intensive care unit; study
      protocol for a prospective cohort study (I-Fabulous study).
AB  - BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome
      (ACS) have detrimental effects on all organ systems and are associated with
      increased morbidity and mortality in critically ill patients admitted to an
      intensive care unit. Intra-bladder measurement of the intra-abdominal pressure
      (IAP) is currently the gold standard. However, IAH is not always indicative of
      intestinal ischemia, which is an early and rapidly developing complication.
      Sensitive biomarkers for intestinal ischemia are needed to be able to intervene
      before damage becomes irreversible. Gut wall integrity loss, including epithelial
      cell disruption and tight junctions breakdown, is an early event in intestinal
      damage. Intestinal Fatty Acid Binding Protein (I-FABP) is excreted in urine and
      blood specifically from damaged intestinal epithelial cells. Claudin-3 is a
      specific protein which is excreted in urine following disruption of intercellular
      tight junctions. This study aims to investigate if I-FABP and Claudin-3 can be
      used as a diagnostic tool for identifying patients at risk for IAP-related
      complications. METHODS/DESIGN: In a multicenter, prospective cohort study 200
      adult patients admitted to the intensive care unit with at least two risk factors
      for IAH as defined by the World Society of the Abdominal Compartment Syndrome
      (WSACS) will be included. Patients in whom an intra-bladder IAP measurement is
      contra-indicated or impossible and patients with inflammatory bowel diseases that
      may affect I-FABP levels will be excluded. The IAP will be measured using an
      intra-bladder technique. During the subsequent 72 hours, the IAP measurement will
      be repeated every six hours. At these time points, a urine and serum sample will
      be collected for measurement of I-FABP and Claudin-3 levels. Clinical outcome of
      patients during their stay at the intensive care unit will be monitored using the
      Sequential Organ Failure Assessment (SOFA) score. DISCUSSION: Successful
      completion of this trial will provide evidence on the eventual role of the
      biomarkers I-FABP and Claudin-3 in predicting the risk of IAP-associated adverse
      outcome. This may aid early (surgical) intervention. TRIAL REGISTRATION: The
      trial is registered at the Netherlands Trial Register (NTR4638).

PMID- 25591788
TI  - Biological roles of CCAAT/Enhancer-binding protein delta during inflammation.
AB  - CCAAT/enhancer-binding protein delta (CEBPD) belongs to the CCAAT/enhancer
      binding protein family, and these proteins function as transcription factors in
      many biological processes, including cell differentiation, motility, growth
      arrest, proliferation, cell death, metabolism and immune responses. The
      functional diversity of CEBPD depends, in part, on the cell type and cellular
      context, which indicates that CEBPD could interpret a variety of cues to adjust
      cellular responses in specific situations. Here, we review the regulation of the
      CEBPD gene and its function in response to inflammatory stimuli. We also address
      its effects in inflammation-related diseases through a discussion of its recently
      discovered downstream targets. Regarding to the previous discoveries and new
      insights in inflammation-associated diseases, suggesting CEBPD could also be a
      central gene in inflammation. Importantly, the results of this study indicate
      that the investigation of CEBPD could open a new avenue to help better understand
      the inflammatory response. 

PMID- 25591789
TI  - A lacZ reporter gene expression atlas for 313 adult KOMP mutant mouse lines.
AB  - Expression of the bacterial beta-galactosidase reporter gene (lacZ) in the vector
      used for the Knockout Mouse Project (KOMP) is driven by the endogenous promoter
      of the target gene. In tissues from KOMP mice, histochemical staining for LacZ
      enzyme activity can be used to determine gene expression patterns. With this
      technique, we have produced a comprehensive resource of gene expression using
      both whole mount (WM) and frozen section (FS) LacZ staining in 313 unique KOMP
      mutant mouse lines. Of these, ~ 80% of mutants showed specific staining in one or
      more tissues, while ~ 20% showed no specific staining, ~ 13% had staining in only
      one tissue, and ~ 25% had staining in >6 tissues. The highest frequency of
      specific staining occurred in the brain (~ 50%), male gonads (42%), and kidney
      (39%). The WM method was useful for rapidly identifying whole organ and some
      substructure staining, while the FS method often revealed substructure and
      cellular staining specificity. Both staining methods had >90% repeatability in
      biological replicates. Nonspecific LacZ staining occurs in some tissues due to
      the presence of bacteria or endogenous enzyme activity. However, this can be
      effectively distinguished from reporter gene activity by the combination of the
      WM and FS methods. After careful annotation, LacZ staining patterns in a high
      percentage of mutants revealed a unique structure-function not previously
      reported for many of these genes. The validation of methods for LacZ staining,
      annotation, and expression analysis reported here provides unique insights into
      the function of genes for which little is currently known.

PMID- 25591790
TI  - Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer.
AB  - Although the early diagnosis of gastric cancer provides the opportunity for
      curative endoscopic resection, comprehensive screening endoscopy would be
      invasive and expensive. To date, there is a complete absence of clinically useful
      gastric cancer biomarkers. With the goal of discovering noninvasive biomarkers
      for the early diagnosis of gastric cancer, we have conducted a case-control study
      using urine samples from individuals with gastric cancer versus healthy control
      samples. Of the enrolled 106 patients from September, 2012 to April, 2013, a
      cohort of 70 patients composed of 35 patients with gastric cancer and 35 age- and
      sex-matched healthy controls was analyzed. The gastric cancer group was composed
      of stage IA of 62.9% (22/35). The urinary levels of MMP-9/NGAL complex (uMMP
      9/NGAL) and ADAM12 (uADAM12) were significantly higher in the gastric cancer
      group compared with the healthy control group as determined by monospecific
      ELISAs (uMMP-9/NGAL: median, 85 pg/mL vs. 0 pg/mL; P = 0.020; uADAM12: median,
      3.35 ng/mL vs. 1.44 ng/mL; P < 0.001). Multivariate analysis demonstrated that
      both uMMP-9/NGAL and uADAM12 were significant, independent diagnostic biomarkers
      for gastric cancer. Moreover, MMP-9/NGAL activity was significantly elevated as
      determined by gelatin zymography. The combination of uMMP-9/NGAL with uADAM12
      distinguished between control samples and gastric cancer samples with an AUC of
      0.825 (P < 0.001) in an ROC analysis. Significantly, immunohistochemical analyses
      demonstrated a high coexpression of MMP-9 and NGAL (P < 0.001) and high
      expression of ADAM12 (P < 0.001) in gastric cancer tissues compared with adjacent
      normal tissues (N = 35). In summary, uMMP-9/NGAL and uADAM12 are potential
      noninvasive biomarkers for gastric cancer, including early-stage disease.

PMID- 25591791
TI  - Being a bridge: Swedish antenatal care midwives' encounters with Somali-born
      women and questions of violence; a qualitative study.
AB  - BACKGROUND: Violence against women is associated with serious health problems,
      including adverse maternal and child health. Antenatal care (ANC) midwives are
      increasingly expected to implement the routine of identifying exposure to
      violence. An increase of Somali born refugee women in Sweden, their reported
      adverse childbearing health and possible links to violence pose a challenge to
      the Swedish maternity health care system. Thus, the aim was to explore ways ANC
      midwives in Sweden work with Somali born women and the questions of exposure to
      violence. METHODS: Qualitative individual interviews with 17 midwives working
      with Somali-born women in nine ANC clinics in Sweden were analyzed using thematic
      analysis. RESULTS: The midwives strived to focus on the individual woman beyond
      ethnicity and cultural differences. In relation to the Somali born women, they
      navigated between different definitions of violence, ways of handling adversities
      in life and social contexts, guided by experience based knowledge and collegial
      support. Seldom was ongoing violence encountered. The Somali-born women's'
      strengths and contentment were highlighted, however, language skills were
      considered central for a Somali-born woman's access to rights and support in the
      Swedish society. Shared language, trustful relationships, patience, and
      networking were important aspects in the work with violence among Somali-born
      women. CONCLUSION: Focus on the individual woman and skills in inter-cultural
      communication increases possibilities of overcoming social distances. This
      enhances midwives' ability to identify Somali born woman's resources and needs
      regarding violence disclosure and support. Although routine use of professional
      interpretation is implemented, it might not fully provide nuances and social
      safety needed for violence disclosure. Thus, patience and trusting relationships
      are fundamental in work with violence among Somali born women. In collaboration
      with social networks and other health care and social work professions, the
      midwife can be a bridge and contribute to increased awareness of rights and
      support for Somali-born women in a new society.

PMID- 25591793
TI  - Evolution of external genital development. Preface.

PMID- 25591792
TI  - Cervicovaginal cytology in patients undergoing pelvic radiotherapy using the
      Focalpoint system: results from the RODEO study.
AB  - BACKGROUND: Evaluate the performance of the Focalpoint system in identifying and
      classifying cervical cytology alterations from samples collected from patients
      treated with Radiotherapy (RT). METHODS: The reproducibility of manual and
      automated screening by cytotechnologists using the BD Focalpoint GS Imaging
      System was examined. Samples were collected from May 2010 to August 2011.
      RESULTS: A total of 378 treated with RT and 8,967 cytology samples from patients
      without previous RT, were evaluated. The kappa values for cytological diagnoses
      read manually and automated in cases without previous RT were as follows: < ASC-H
      vs. >= ASC-H = 0.71; < LSIL vs. >= LSIL = 0.66; and < HSIL vs. >= HSIL = 0.67.
      The kappa for cytological diagnoses in post-RT women have showed: < ASC-H vs. >=
      ASC-H = 0.71; < LSIL vs. >= LSIL = 0.65; < HSIL vs. >= HSIL = 0.57. CONCLUSIONS:
      There was no significant difference among the kappa values we found. Post-RT
      cytology showed small diagnostic agreement between manual and automated
      examination. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_231.

PMID- 25591794
TI  - Biogeographic variation in the diet and behaviour of Cercopithecus mitis.
AB  - Primate species are characterised by variation in foraging behaviour and dietary
      composition across their geographic range. Here we examine how ecological
      conditions account for variation in the behavioural ecology of a widespread
      arboreal guenon, Cercopithecus mitis. Although substantial variation existed in
      time budgets, group size, home range and day journey length, clear biogeographic
      patterns were not apparent. In contrast, dietary variation was correlated with
      underlying climatic conditions. Temperature seasonality, which tends to increase
      with latitude, was significantly positively related to the proportion of fruit in
      the diet and negatively related to the proportion of animal matter. Both dietary
      components were 'preferred' foods, with the variability between populations
      reflecting the availability of different food types across their geographic
      range. Although we found no significant relationships between climate and the
      proportion of leaves in the diet, the ability for C. mitis to vary its diet to
      include a diversity of food types, and to incorporate a significant proportion of
      leaves when preferred sources are scarce, likely underpins its ability to survive
      across such a large distribution.

PMID- 25591795
TI  - pH-sensitive microemulsion-based gels for removal of colonic ammonia: a novel
      preventative oral preparation for hepatic encephalopathy in rats.
AB  - Microemulsions with limited stability in mimetic gastrointestinal environments
      have previously demonstrated potential for the effective removal of ammonia from
      artificial colonic fluid. Specialized pH-sensitive microemulsion-based gels for
      the removal of colonic ammonia (MBG-RCA), however, possess relative stability in
      the gastrointestinal (GI) tract of normal rats, indicating potential use in in
      vivo applications. An investigation of the effects of oral MBG-RCA was conducted
      in order to evaluate the reduction of intestinal ammonia and the prevention of
      hepatic encephalopathy (HE) in rat models. Eighty rats were allocated into eight
      4-day treatment groups: The HE model (intraperitoneal injection of thioacetamide)
      group; the high-, medium- and low-dose MBG-RCA therapeutic groups (15, 10 and 5
      ml/kg MBG-RCA, respectively); and the normal, blank, lactulose and acetic acid
      control groups, each of which received daily treatment administration. Oral MBG
      RCA effects were identified using behavioral monitoring observed by an infrared
      night vision supervisory control system, electroencephalograms, blood ammonia
      levels, intestinal ammonia levels, liver functionality and pathological
      observation. High- and medium-dose oral administrations of MBG-RCA significantly
      decreased the blood and intestinal ammonia levels (P<0.05), improved liver
      functionality and reduced the clinical manifestations of HE in rats. MBG-RCA
      demonstrated high clearance of rat colonic ammonia while maintaining sufficient
      stability in the GI tract, indicating the potential for the development of new
      clinically relevant oral preparations for the prevention of HE. Additionally,
      such preparations are advantageous in that ammonia is eliminated without the
      production of potentially harmful metabolic byproducts.

PMID- 25591796
TI  - Relationship between meteorological conditions and respiratory syncytial virus in
      a tropical country.
AB  - This study aimed to determine which meteorological conditions are associated with
      respiratory syncytial virus (RSV) isolates in a population of children
      hospitalized with acute lower respiratory infection (ALRI) in Bogota, Colombia.
      In an analytical cross-sectional study, links were examined between the number of
      monthly RSV infections and monthly average climatic variation (temperature,
      relative humidity, rainfall, wind speed, solar radiation) between 1 January 2010
      and 30 April 2011 in a population of hospitalized children aged <3 years with
      ALRI caused by RSV. Out of a total of 1548 children included in the study (mean
      age 9.2 +/- 8.5 months), 1194 (77.1%) presented RSV infection during the 3-month
      period from March to May. In the multivariate analysis, after controlling for
      wind speed, relative humidity, and solar radiation, monthly average temperature
      [incident rate ratio (IRR) 3.14, 95% confidence interval (CI) 1.56-6.30, P =
      0.001] and rainfall (IRR 1.008, 95% CI 1.00-1.01, P = 0.048) were independently
      associated with the monthly number of RSV infections. In conclusion, in Bogota, a
      tropical Latin American city, average temperature and rainfall are the
      meteorological variables most strongly associated with RSV isolation in children
      hospitalized with ALRI in the city. 

PMID- 25591797
TI  - Diphenylene iodonium interferes with cell cycle progression and induces apoptosis
      by modulating NAD(P)H oxidase/ROS/cell cycle regulatory pathways in Burkitt's
      lymphoma cells.
AB  - Infection with Epstein-Barr virus (EBV) and its encoded latent membrane protein 1
      (LMP1) play oncogenic roles in Burkitt's lymphoma (BL). Flow cytometry was used
      to measure cellular reactive oxygen species (ROS) concentrations, and cellular
      lactate generation and diphenylene iodonium (DPI) cytotoxicity were determined by
      analyzing lactate concentrations and cell viability. We also measured NAD(P)H
      oxidase (NOX) activity. Reverse transcriptase PCR and qPCR assays were used to
      analyze LMP1 levels, and protein expression was measured by immunoblotting. In
      the present study, EBV was able to induce NOX activity and ROS generation in the
      BL cells. Inhibition of NOX activity by DPI suppressed ROS levels and elevated
      lactate levels. DPI treatment first resulted in a G2-M phase cell cycle arrest
      and then induced significant apoptosis. Immunoblot analysis demonstrated that DPI
      suppressed the expression of c-Myc and Cdc25A within 6 h, which may have caused
      the cell cycle arrest. Collectively, these findings indicate a close relationship
      between EBV infection and NOX activation, permitting a deeper understanding of
      ROS inhibition in cell cycle regulation and providing a novel therapeutic target
      for BL treatment.

PMID- 25591798
TI  - Selective cyclooxygenase-1 inhibition by p6 and gastrotoxicity: preliminary
      investigation.
AB  - BACKGROUND/AIMS: Gastrointestinal damage (GD) is commonly associated with the
      inhibition of cyclooxygenase (COX)-1, one of the two known COXs, by traditional
      non-steroidal anti-inflammatory drugs. More recent evidences have proven that GD
      is caused by the simultaneous inhibition of the two COXs. This study was designed
      to evaluate the effect of the selective COX-1 inhibition on gastric integrity.
      METHODS: GD was evaluated in male CD1 mice. Drugs were administered by gastric
      gavage at a dose of 50 mg/kg (injection volume of 100 ul). Control mice received
      an equal volume of the vehicle (10% ethanol). Each mouse, in groups of at least 6
      mice, received one dose/day for 5 days. RESULTS: In Western blot analysis, COX-1
      expression levels were found to be significantly reduced in mice treated with 3
      (5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6) in comparison to mice
      pretreated with aspirin (ASA), which exhibited higher levels of COX-1, thus
      confirming the high selectivity of P6 towards COX-1 enzyme inhibition. Mucosal
      sections obtained from ASA-treated mice showed breaks in the epithelial barrier
      and a marked alteration of foveolae and gastric glands, whereas stomachs isolated
      from mice sacrificed after 5 days of chronic administration of P6 (at a dose of
      up to 50 mg/kg/day) showed sporadic transient mucosal hyperemia and did not seem
      to display any significant gastric damage. CONCLUSIONS: The selective COX-1
      inhibition by P6 does not cause gastric damage in mice but preserves mucosal
      integrity.

PMID- 25591799
TI  - A phase Ib study of the VEGF receptor tyrosine kinase inhibitor tivozanib and
      modified FOLFOX-6 in patients with advanced gastrointestinal malignancies.
AB  - BACKGROUND: Tivozanib hydrochloride (tivozanib) is a potent and selective
      tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors
      with antitumor activity additive to 5-fluorouracil in preclinical models. This
      study was conducted to determine maximum tolerated dose (MTD), dose-limiting
      toxicities (DLTs), pharmacokinetics (PKs), and antitumor activity of escalating
      doses of tivozanib with a modified (m)FOLFOX-6 (leucovorin, 5-fluorouracil [5
      FU], and 85 mg/kg(2) oxaliplatin) regimen in patients with advanced
      gastrointestinal tumors. PATIENTS AND METHODS: Tivozanib was administered orally
      once daily for 21 days in 28-day cycles, with mFOLFOX-6 administered every 14
      days. Patients were allowed to continue tivozanib after discontinuation of
      mFOLFOX-6. RESULTS: Thirty patients were assigned to tivozanib 0.5 mg (n = 9),
      1.0 mg (n = 3), or 1.5 mg (n = 18) with mFOLFOX-6. Patients received a median of
      5.2 (range, 0.03-26.9) months of tivozanib. DLTs were observed in 2 patients:
      Grade 3/4 transaminase level increases with tivozanib 0.5 mg, and Grade 3
      dizziness with tivozanib 1.5 mg. Other Grade 3/4 adverse events included
      hypertension (n = 8), fatigue (n = 8), and neutropenia (n = 6). MTD for tivozanib
      with mFOLFOX-6 was confirmed as 1.5 mg. No PK interactions between tivozanib and
      mFOLFOX-6 were observed. One patient had an ongoing clinical complete response,
      10 had a partial response, and 11 obtained prolonged stable disease. CONCLUSION:
      Tivozanib and mFOLFOX-6 is feasible and appears to be safe. The recommended dose
      for tivozanib with mFOLFOX-6 is 1.5 mg/d. Observed clinical activity merits
      further exploration in gastrointestinal tumors.

PMID- 25591800
TI  - Circulating endothelial cells and their subpopulations: role as predictive
      biomarkers in antiangiogenic therapy for colorectal cancer.
AB  - Several anticancer therapies have been developed to block angiogenesis, a key
      mechanism in tumor growth and metastasis. The predominantly cytostatic action of
      these compounds makes an assessment of their clinical activities inadequate if
      based only on the reduction of the tumor dimensions, as this may not reflect
      their true biologic efficacy. Thus, it is crucial to identify biomarkers that
      permit the recognition of potentially responsive subjects and to spare toxicity
      in those who are unlikely to benefit from treatment. Circulating endothelial
      cells (CECs) have been recently indicated as potential surrogate biomarkers of
      angiogenesis in several types of cancer. The possibility of rapidly quantifying
      these cells represents a promising tool for monitoring the clinical outcome of
      tumors with the potential to assess response to various treatments. However, the
      identification and quantification of CECs is technically difficult and not well
      standardized. A variety of methods to detect CECs in patients with solid tumors
      have been used; these are based on different technical approaches, combinations
      of surface markers, sample handling, and staining protocols. With an expanding
      interest in the field of potential clinical applications for CECs in oncology,
      the development of standardized protocols for analysis is mandatory. The aim of
      this review was to critically summarize the available data concerning the
      clinical value of CECs and their subpopulations as biomarkers of antiangiogenic
      therapy in patients with metastatic colorectal cancer. 

PMID- 25591801
TI  - Updated periodic evaluation of standardized neurointensive care shows that it is
      possible to maintain a high level of favorable outcome even with increasing mean
      age.
AB  - BACKGROUND: Periodic evaluation of neurointensive care (NIC) is important. There
      is a risk that quality of daily care declines and there may also be unrecognized
      changes in patient characteristics and management. The aim of this work was to
      investigate the characteristics and outcome for traumatic brain injury (TBI)
      patients in the period 2008-2009 in comparison with 1996-1997 and to some extent
      also with earlier periods. METHODS: TBI patients 16-79 years old admitted from
      2008 to 2009 were selected for the study. Glasgow Coma Scale Motor score at
      admission (GCS M), radiology, surgery, and outcome (Glasgow Outcome Extended
      Scale) were collected from Uppsala Traumatic Brain Injury Register. RESULTS: The
      study included 148 patients (mean age, 45 years). Patients >60 years old
      increased from 16 % 1996-1997 to 30 % 2008-2009 (p < 0.01). The proportion of GCS
      M 4-6 were similar, 92 vs. 93 % (NS). In 1996-1997 patients, 73 % had diffuse
      injury (Marshall classification) compared to 77 % for the 2008-2009 period (NS).
      More patients underwent surgery during 2008-2009 (43 %) compared to 1996-1997 (32
      %, p < 0.05). Good recovery increased and mortality decreased substantially from
      1980-1981 to 1987-1988 and to 1996-1997, but then the results were unchanged in
      the 2008-2009 period, with 73 % favorable outcome and 11 % mortality. Mortality
      increased in GCS M 6-4, from 2.8 % in 1996-1997 to 10 % in 2008-2009 (p < 0.05);
      most of the patients that died had aggravating factors, e.g., high age,
      malignancy. CONCLUSIONS: A large-proportion favorable outcome was maintained
      despite that patients >60 years with poorer prognosis doubled, indicating that
      the quality of NIC has increased or at least is unchanged. More surgery may have
      contributed to maintaining the large proportion of favorable outcome. For future
      improvements, more knowledge about TBI management in the elderly is required.

PMID- 25591802
TI  - Changes of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in
      the model of experimental acute hydrocephalus in rabbits.
AB  - BACKGROUND: To study the integrity of white matter, we investigated the
      correlation between the changes in neuroradiological and morphological parameters
      in an animal model of acute obstructive hydrocephalus. METHODS: Hydrocephalus was
      induced in New Zealand rabbits (n = 10) by stereotactic injection of kaolin into
      the lateral ventricles. Control animals received saline in place of kaolin (n =
      10). The progression of hydrocephalus was assessed using magnetic resonance
      imaging. Regional fractional anisotropy (FA) and the apparent diffusion
      coefficient (ADC) were measured in several white matter regions before and after
      the infusion of kaolin. Morphology of myelinated nerve fibers as well as of the
      blood-brain barrier were studied with the help of transmission electron
      microscopy (TEM) and light microscopy. RESULTS: Compared with control animals,
      kaolin injection into the ventricles resulted in a dramatic increase in
      ventricular volume with compression of basal cisterns, brain shift and
      periventricular edema (as observed on magnetic resonance imaging [MRI]). The
      values of ADC in the periventricular and periaqueductal areas significantly
      increased in the experimental group (P < 0.05). FA decreased by a factor of 2 in
      the zones of periventricular, periaqueductal white matter and corpus collosum.
      Histological analysis demonstrated the impairment of the white matter and
      necrobiotic changes in the cortex. Microsctructural alterations of the myelin
      fibers were further proved with the help of TEM. Blood-brain barrier
      ultrastructure assessment showed the loss of its integrity. CONCLUSIONS: The
      study demonstrated the correlation of the neuroradiological parameters with
      morphological changes. The abnormality of the FA and ADC parameters in the
      obstructive hydrocephalus represents a significant implication for the
      diagnostics and management of hydrocephalus in patients.

PMID- 25591803
TI  - Solitary lesions of the clivus: what else besides chordomas? An extensive
      clinical outlook on rare pathologies.
AB  - BACKGROUND: Solitary non-chordomatous lesions of the clivus are rare pathologies,
      which represent a diagnostic challenge. This study provides an overview of the
      clinical, radiological and prognostic characteristics of non-chordomatous clival
      lesions, highlighting current therapeutic options. METHODS: Twenty-two non
      chordomatous lesions of the clivus were collected. A retrospective analysis of
      clinical and radiological patterns as well as survival data was conducted.
      RESULTS: Clinical presentation was a result of local mass effect. Imaging
      features, although mainly specific, were not always diagnostic. Extent of surgery
      was gross total in 45.5 % of cases. Depending on the histology, biological
      behaviour and presence of seeding, adjuvant treatment was performed, tailoring
      the treatment strategy to the single patient. CONCLUSIONS: Solitary non
      chordomatous lesions of the clival bone are more prevalent than expected. They
      should be approached with a correct differential diagnosis, considering specific
      epidemiological, radiological, and histopathological characteristics, to minimise
      diagnostic bias and allow the planning of the best treatment strategy.

PMID- 25591804
TI  - Editorial re: "side errors in neurosurgery and human factors training".

PMID- 25591805
TI  - Do schools in Quebec foster healthy eating? An overview of associations between
      school food environment and socio-economic characteristics.
AB  - OBJECTIVE: A school environment that encourages students to opt for food with
      sound nutritional value is both essential and formative in ensuring that young
      people adopt healthy eating habits. The present study explored the associations
      between the socio-economic characteristics of the school environment and the
      school food environment. DESIGN: A cross-sectional survey was conducted in 2008
      2009. Descriptive and bivariate analyses were performed on data from public
      primary and secondary schools. SETTING: Quebec, Canada. The school food offering
      was observed directly and systematically by trained research assistants.
      Interviews were conducted to fully describe food offerings in the schools and
      schools' child-care services. SUBJECTS: A two-stage stratified sampling was used
      to build a representative sample of 143 French-speaking public schools. The
      response rate was 66.2%. RESULTS: The primary and secondary schools in low
      density areas were more likely to be located near diners (primary: P=0.018;
      secondary: P=0.007). The secondary schools in deprived areas were less likely to
      have a regular food committee (P=0.004), to seek student input on menu choices
      (P=0.001) or to have a long lunch period (P=0.010). The primary schools in
      deprived areas were less likely to have a food service (P=0.025) and their meal
      periods were shorter (P=0.033). CONCLUSIONS: The schools in areas with lower
      socio-economic status provided an environment less favourable for a healthy diet.
      From a public health perspective, the results of this analysis could assist
      policy makers and managers to identify actions to support the creation of
      favourable school environments.

PMID- 25591806
TI  - Informed consent for HIV cure research in South Africa: issues to consider.
AB  - BACKGROUND: South Africa has made great progress in the development of HIV/AIDS
      testing, treatment and prevention campaigns. Yet, it is clear that prevention and
      treatment campaigns alone are not enough to bring this epidemic under control.
      DISCUSSION: News that the "Berlin patient" and the "Mississippi baby" have both
      been "cured" of HIV brought hope to people living with HIV/AIDS in South Africa
      that a cure for HIV/AIDS is within reach. Despite the recent setbacks announced
      in the "Mississippi Baby" case, protocols aimed at curing HIV/AIDS are being
      developed in South Africa. However with evidence to suggest that participants in
      clinical trials do not understand the basic concepts in the informed consent
      process, there is concern that future participants in HIV/AIDS cure research will
      lack comprehension of the basic elements of future clinical trials that aims to
      cure HIV/AIDS and confuse research with clinical care. SUMMARY: Research ethics
      committees have an important role to play in ensuring that participants
      understand the basic concepts discussed in the informed consent process, that
      they understand that research is not clinical care and they are unlikely to
      benefit from any early phase trials seeking to cure HIV/AIDS.

PMID- 25591807
TI  - Evaluating the sensitivity of the optimization of acquisition geometry to the
      choice of reconstruction algorithm in digital breast tomosynthesis through a
      simulation study.
AB  - Due to the limited number of views and limited angular span in digital breast
      tomosynthesis (DBT), the acquisition geometry design is an important factor that
      affects the image quality. Therefore, intensive studies have been conducted
      regarding the optimization of the acquisition geometry. However, different
      reconstruction algorithms were used in most of the reported studies. Because each
      type of reconstruction algorithm can provide images with its own image
      resolution, noise properties and artifact appearance, it is unclear whether the
      optimal geometries concluded for the DBT system in one study can be generalized
      to the DBT systems with a reconstruction algorithm different to the one applied
      in that study. Hence, we investigated the effect of the reconstruction algorithm
      on the optimization of acquisition geometry parameters through carefully designed
      simulation studies. Our results show that using various reconstruction
      algorithms, including the filtered back-projection, the simultaneous algebraic
      reconstruction technique, the maximum-likelihood method and the total-variation
      regularized least-square method, gave similar performance trends for the
      acquisition parameters for detecting lesions. The consistency of system ranking
      indicates that the choice of the reconstruction algorithm may not be critical for
      DBT system geometry optimization. 

PMID- 25591808
TI  - Long noncoding RNA PEG10 regulates proliferation and invasion of esophageal
      cancer cells.
AB  - Long chain noncoding RNAs (LncRNAs), a class of noncoding RNA nucleotides longer
      than 200 bp, have important roles in a variety of biological processes.
      Accumulating evidence has confirmed the involvement of LncRNAs in cancer
      initiation, development and progression. We investigated the expression of LncRNA
      PEG10 in a cohort of esophageal carcinomas to assess its impact on esophageal
      cancer cell proliferation, apoptosis and invasion. Quantitaive reverse
      transcription polymerase chain reaction assays were used to quantify LncRNA PEG10
      expression levels in 43 paired EC samples and adjacent non-neoplastic tissues.
      Cell growth, apoptosis and Transwell invasion assays were used to evaluate the
      effects of LncRNA PEG10 on esophageal cancer cells. LncRNA PEG10 was expressed at
      higher levels in esophageal cancer tissues than in adjacent non-neoplastic
      tissues (P<0.05). This relatively high expression was significantly associated
      with the occurrence of lymph node metastases (P<0.05). Apoptosis and migration
      rates were significantly decreased in two esophageal cancer cell lines (EC9706
      and KYSE150) transfected with si-LncRNA PEG10 (P<0.05). Downregulation of LncRNA
      PEG10 decreased the expression of PEG10 (P<0.05). Our results indicated that
      LncRNA PEG10 is upregulated in esophageal cancer tissues, and its downregulation
      inhibits proliferation and invasion, and promotes apoptosis in esophageal cancer
      cells. LncRNA PEG10 may serve as a therapeutic agent in esophageal cancer. 

PMID- 25591809
TI  - Pigment epithelium-derived factor enhances tumor response to radiation through
      vasculature normalization in allografted lung cancer in mice.
AB  - This study aimed to explore the potential therapeutic effects of the combination
      of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The
      Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF
      and PEDF combined with radiation. The morphologic changes of tumor vasculature
      and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition
      of tumor growth was observed when radiation was applied between the 3rd and 7th
      day (the vasculature normalization window) after the initiation of PEDF
      treatment. During the vasculature normalization window, the tumor blood vessels
      in PEDF-treated mice were less tortuous and more uniform than those in the LLC
      allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness
      of the basement membrane was remarkably reduced and pericyte coverage was
      significantly increased with the PEDF treatment. We also found that tumor hypoxic
      fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting
      improved intratumoral oxygenation. Taken together, our results show that PEDF
      improved the effects of radiation therapy on LLC allografts by inducing a
      vascular normalization window from the 3rd to the 7th day after PEDF treatment.
      Our findings provide a basis for treating lung cancer with the combination of
      PEDF and radiation. 

PMID- 25591811
TI  - Gastro-oesophageal reflux disease in children: NICE guidance.

PMID- 25591810
TI  - Manufacture of T cells using the Sleeping Beauty system to enforce expression of
      a CD19-specific chimeric antigen receptor.
AB  - T cells can be reprogrammed to redirect specificity to tumor-associated antigens
      (TAAs) through the enforced expression of chimeric antigen receptors (CARs). The
      prototypical CAR is a single-chain molecule that docks with TAA expressed on the
      cell surface and, in contrast to the T-cell receptor complex, recognizes target
      cells independent of human leukocyte antigen. The bioprocessing to generate
      CAR(+) T cells has been reduced to clinical practice based on two common steps
      that are accomplished in compliance with current good manufacturing practice.
      These are (1) gene transfer to stably integrate the CAR using viral and nonviral
      approaches and (2) activating the T cells for proliferation by crosslinking CD3
      or antigen-driven numeric expansion using activating and propagating cells
      (AaPCs). Here, we outline our approach to nonviral gene transfer using the
      Sleeping Beauty system and the selective propagation of CD19-specific CAR(+) T
      cells on AaPCs. 

PMID- 25591813
TI  - 2D protein arrays induce 3D in vivo-like assemblies of cells.
AB  - We report on the ability of two-dimensional protein crystals to induce the
      formation of homo- and heterotypic multicellular spheroids (MCSs) which resemble
      the morphology and hierarchical organization of living tissues and tumours. We
      have systematically studied the influence of the initial cell density and
      incubation time on the kinetics of spheroid growth and spheroid lifespan. Hereby
      a novel methodology has been established to produce MCSs on protein-based
      molecular layers. 

PMID- 25591812
TI  - Association of de novo dipstick albuminuria with severe acute kidney injury in
      critically ill septic patients.
AB  - BACKGROUND: Acute kidney injury (AKI) occurs frequently in septic patients.
      Albuminuria may play a role as an early marker of septic AKI. The potential
      association between de novo dipstick albuminuria (DA) and septic AKI has not been
      examined. METHODS: We conducted a single-center observational cohort study of 423
      critically ill septic patients without chronic kidney disease (CKD) or prior
      positive DA within 3 months before admission. The association between de novo DA
      within the first 24 h of presentation and AKI at 72 h was examined. RESULTS: AKI
      was identified in 268/423 (63%) patients and 20/423 (4.7%) required dialysis. De
      novo DA was associated with AKI (univariate OR 1.91; 95% CI 1.27-2.86, p =
      0.002). The association persisted in a multivariate logistic regression model
      adjusted for demographics, baseline kidney function, comorbidities, critical
      illness parameters, and exposure to nephrotoxins (adjusted OR 1.87; 95% CI 1.21
      2.89, p = 0.005). The association between de novo DA and AKI was stronger for
      severe AKI, i.e. Acute Kidney Injury Network (AKIN) stage 3 (adjusted OR 2.99;
      95% CI 1.52-5.85, p = 0.001) and AKIN stage 2 (adjusted OR 1.79; 95% CI 1.002
      3.21, p = 0.049) but not AKIN stage 1 (adjusted OR 1.41; 95% CI 0.87-2.29, p =
      0.16). CONCLUSIONS: De novo DA within the first 24 h of admission was
      independently associated with severe AKI in critically ill septic patients.
      Future studies are required to fully elucidate the utility of DA testing in the
      early detection and stratification of AKI.

PMID- 25591815
TI  - Role of Immunity and Inflammation in the Pathophysiology of Neurodegenerative
      Diseases.
AB  - Neurodegenerative diseases are the result of progressive loss of neurons and
      axons in the central nervous system (CNS), which can lead to cognition and motor
      dysfunction. It is well known that CNS inflammation and immune activation play a
      major role in the pathophysiology of neurodegenerative diseases. Although the
      blood-brain barrier (BBB) is able to protect the CNS from immune activation, it
      becomes more permeable during inflammation, which renders the brain vulnerable to
      infections. A better understanding of the interaction between inflammatory
      mediators, such as cytokines, and the activated immune response, including
      astrocytes and microglia, is critical for the development of new therapeutic
      strategies for neurodegenerative diseases. This review first describes the role
      of innate immune activation in neurodegenerative diseases and illustrates the
      factors that contribute to the communication between the CNS and the immune
      system. A closer look is given at the role of the BBB in inflammation and
      immunity, as well as at the animal models used to study inflammation in
      neurodegenerative diseases. Finally, this review outlines the key pathways and
      biological mechanisms involved in CNS diseases, with a particular focus on
      multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD).

PMID- 25591814
TI  - Biomimetic synthesis of struvite with biogenic morphology and implication for
      pathological biomineralization.
AB  - Recent studies have found that certain urinary proteins can efficiently inhibit
      stone formation. These discoveries are significant for developing effective
      therapies for stone disease, but the inhibition mechanism of crystallization
      remains elusive. In the present study, polyaspartic acid (PASP) was employed as a
      model peptide to investigate the effect of urinary proteins on the
      crystallization and morphological evolution of struvite. The results demonstrate
      that selective adsorption/binding of PASP onto the {010} and {101} faces of
      struvite crystals results in arrowhead-shaped morphology, which further evolves
      into X-shaped and unusual tabular structures with time. Noticeably, these
      morphologies are reminiscent of biogenic struvite morphology. Concentration
      dependent experiments show that PASP can inhibit struvite growth and the
      inhibitory capacity increases with increasing PASP concentration, whereas
      aspartic acid monomers do not show a significant effect. Considering that PASP is
      a structural and functional analogue of the subdomains of aspartic acid-rich
      proteins, our results reveal that aspartic acid-rich proteins play a key role in
      regulating biogenic struvite morphology, and aspartic acid residues contribute to
      the inhibitory capacity of urinary proteins. The potential implications of PASP
      for developing therapeutic agents for urinary stone disease is also discussed. 

PMID- 25591817
TI  - Establishing implantation uncertainties for focal brachytherapy with I-125 seeds
      for the treatment of localized prostate cancer.
AB  - BACKGROUND: The efficacy of focal continuous low dose-rate brachytherapy (CLDR
      BT) for prostate cancer requires that appropriate margins are applied to ensure
      robust target coverage. In this study we propose a method to establish such
      margins by emulating a focal treatment in patients treated with CLDR-BT to the
      entire gland. MATERIAL AND METHODS: In 15 patients with localized prostate
      cancer, prostate volumes and dominant intra-prostatic lesions were delineated on
      pre-treatment magnetic resonance imaging (MRI). Delineations and MRI were
      registered to trans-rectal ultrasound images in the operating theater. The
      patients received CLDR-BT treatment to the total prostate volume. The
      implantation consisted of two parts: an experimental focal plan covering the
      dominant intra-prostatic lesion (F-GTV), followed by a plan containing additional
      seeds to achieve entire prostate coverage. Isodose surfaces were reconstructed
      using follow-up computed tomography (CT). The focal dose was emulated by
      reconstructing seeds from the focal plan only. The distance to agreement between
      planned and delivered isodose surfaces and F-GTV coverage was determined to
      calculate the margin required for robust treatment. RESULTS: If patients had been
      treated only focally, the target volume would have been reduced from an average
      of 40.9 cm3 for the entire prostate to 5.8 cm3 for the focal plan. The D90 for
      the F-GTV in the focal plan was 195+/-60 Gy, the V100 was 94% [range 71-100%].
      The maximum distance (cd95) between the planned and delivered isodose contours
      was 0.48 cm. CONCLUSIONS: This study provides an estimate of 0.5 cm for the
      margin required for robust coverage of a focal target volume prior to actually
      implementing a focal treatment protocol.

PMID- 25591816
TI  - Epidemiology of CTX-M-type extended-spectrum beta-lactamase (ESBL)-producing
      nosocomial -Escherichia coli infection in China.
AB  - BACKGROUND: Escherichia coli is one of the most common clinical pathogens causing
      nosocomial infection. The widespread cefotaxime-beta lactamases (CTX) has
      increased the multidrug resistance (MDR) of E. coli and has brought great trouble
      to the doctor treating the infection. METHODS: ESBL-positive E. coli isolates
      were collected from different hospitals in different areas and the minimal
      inhibitory concentration (MIC) was analyzed by the agar dilution method. The
      resistance gene types were detected using polymerase chain reaction (PCR) and the
      sequence types were determined by multilocus sequence typing (MLST). RESULTS: We
      found that the blaCTX-M-1 group and the blaCTX-M-9 group were the main CTX-M gene
      types, with many kinds of MLST gene types. Except for TEM with high isolate, SHV,
      OXA and VEB were relatively rare, while no PER and GES was detected. Most strains
      may have other resistance mechanisms, and the ESBL positive strains have high
      resistance not only to cephalosporins but also to other kinds of antibiotics.
      CONCLUSION: The study provides wide epidemiological data and enables more
      effective infection control and treatment plans.

PMID- 25591819
TI  - Oncologists' weighing of the benefits and side effects of adjuvant systemic
      therapy: Has it changed over time?

PMID- 25591818
TI  - Predicting patients at risk for pain associated with electrochemotherapy.
AB  - BACKGROUND: Electrochemotherapy describes the use of electric pulses to enhance
      chemotherapy uptake, and has proven highly efficient in treating cutaneous
      metastases. Patients referred for electrochemotherapy present with diverse
      clinical pictures, from multiple small lesions to large, ulcerated lesions. Post
      electrochemotherapy pain has been observed in some patients. The objectives of
      this study were to evaluate pain scores before and after electrochemotherapy, and
      to investigate if patients at risk of post-procedure pain could be identified.
      METHODS: Seven cancer centres in the International Network for Sharing Practices
      on Electrochemotherapy (INSPECT) consecutively and prospectively reported to a
      common database. Electrochemotherapy consisted of intratumoural or intravenous
      injection of bleomycin, followed by delivery of electric pulses in local or
      general anesthesia. RESULTS: Of 121 patients 39% had metastatic melanoma, 18%
      squamous cell carcinoma, 16% breast cancer, 13% basal-cell carcinoma, and 14%
      other malignancies. Median size of the largest nodules was 2.3 cm (range 0.3-40
      cm). A majority of patients presented with low pain scores, and this continued
      through follow-up (74%). A subset of patients had moderate (13%) or severe pain
      (13%) after treatment. Post-procedure pain was statistically significantly
      associated with: 1) moderate or severe pain before treatment (p<0.0001); 2) size
      of the largest treated lesion (p<0.01); 3) previous irradiation (p<0.02); and 4)
      high treatment current value (p<0.0001). CONCLUSION: The majority of patients had
      no or mild pain after electrochemotherapy. Patients at risk for post-procedure
      pain could be identified at the pre-treatment visit, and/or at the time of
      treatment, enabling a pain management strategy for this group.

PMID- 25591821
TI  - p53-induced microRNA-1246 inhibits the cell growth of human hepatocellular
      carcinoma cells by targeting NFIB.
AB  - In recent years, miR-1246 has been identified as a transcriptional target of p53
      in Down syndrome and may provide a new p53-miR-1246-DYRK1A-NFAT pathway in
      cancer. The present study aimed to explore the role of miR-1246 in the
      tumorigenesis of human hepatocellular carcinoma (HCC). We found that wild-type
      p53 regulated the expression of miR-1246 in HCC cell lines, and alteration of miR
      1246 modulated cell proliferation, colony formation ability and apoptosis. The
      nuclear factor I/B (NFIB), an oncogene, was identified as a direct target gene of
      miR-1246 using a fluorescent reporter assay. Overexpression of NFIB abolished the
      regulation of cell apoptosis caused by miR-1246 in HepG2 cells. This finding
      suggests that miR-1246 is regulated by p53 and suppresses the growth of human HCC
      by targeting NFIB. Here, we propose a new p53-miR-1246-NFIB pathway in HCC.

PMID- 25591822
TI  - Evaporative gold nanorod assembly on chemically stripe-patterned gradient
      surfaces.
AB  - Experimentally we explore the potential of using pre-defined motion of a receding
      contact line to control the deposition of nanoparticles from suspension. Stripe
      patterned wettability gradients are employed, which consist of alternating
      hydrophilic and hydrophobic stripes with increasing macroscopic surface energy.
      Nanoparticle suspensions containing nanorods and nanospheres are deposited onto
      these substrates and left to dry. After moving over the pattern and evaporation
      of the solvent, characteristic nanoparticle deposits are found. The liquid
      dynamics has a pronounced effect on the spatial distribution. Nanoparticles do
      not deposit on the hydrophobic regions; there is high preference to deposit on
      the wetting stripes. Moreover, the fact that distributed nanoparticle islands are
      formed suggests that the receding of the contact line occurs in a stick-slip like
      fashion. Furthermore, the formation of liquid bridges covering multiple stripes
      during motion of the droplet over the patterns is modeled. We discuss their
      origin and show that the residue after drying, containing both nanoparticles and
      the stabilizing surfactant, also resembles such dynamics. Finally, zooming into
      individual islands reveals that highly selective phase separation occurs based on
      size and shape of the nanoparticles. 

PMID- 25591820
TI  - Detection of electroporation-induced membrane permeabilization states in the
      brain using diffusion-weighted MRI.
AB  - BACKGROUND: Tissue permeabilization by electroporation (EP) is a promising
      technique to treat certain cancers. Non-invasive methods for verification of
      induced permeabilization are important, especially in deep-seated cancers. In
      this study we evaluated diffusion-weighted magnetic resonance imaging (DW-MRI) as
      a quantitative method for detecting EP-induced membrane permeabilization of brain
      tissue using a rat brain model. MATERIAL AND METHODS: Fifty-four anesthetized
      Sprague-Dawley male rats were electroporated in the right hemisphere, using
      different voltage levels to induce no permeabilization (NP), transient membrane
      permeabilization (TMP), and permanent membrane permeabilization (PMP),
      respectively. DW-MRI was acquired 5 minutes, 2 hours, 24 hours and 48 hours after
      EP. Histology was performed for validation of the permeabilization states. Tissue
      content of water, Na+, K+, Ca2+, and extracellular volume were determined. The
      Kruskal-Wallis test was used to compare the DW-MRI parameters, apparent diffusion
      coefficient (ADC) and kurtosis, at different voltage levels. The two-sample Mann-
      Whitney test with Holm's Bonferroni correction was used to identify pairs of
      significantly different groups. The study was approved by the Danish Animal
      Experiments Inspectorate. RESULTS AND CONCLUSION: Results showed significant
      difference in the ADC between TMP and PMP at 2 hours (p<0.001) and 24 hours
      (p<0.05) after EP. Kurtosis was significantly increased both at TMP (p<0.05) and
      PMP (p<0.001) 5 minutes after EP, compared to NP. Kurtosis was also significantly
      higher at 24 hours (p<0.05) and 48 hours (p<0.05) at PMP compared to NP.
      Physiological parameters indicated correlation with the permeabilization states,
      supporting the DW-MRI findings. We conclude that DW-MRI is capable of detecting
      EP-induced permeabilization of brain tissue and to some extent of differentiating
      NP, TMP and PMP using appropriate scan timing.

PMID- 25591823
TI  - Emulsification synergism in mixtures of polyelectrolyte brush-grafted
      nanoparticles and surfactants.
AB  - HYPOTHESIS: Silica nanoparticles displaying densely grafted poly(2
      (dimethylamino)ethyl methacrylate) (PDMAEMA) polycationic brushes are highly
      efficient emulsifiers, stabilizing oil-in-water emulsions at concentrations as
      low as 0.05 to 0.1 wt%. Adding conventional surfactants is expected to alter
      emulsification efficiency by interacting with grafted nanoparticles in bulk
      and/or at the oil/water interface. EXPERIMENTS: Emulsification efficiency was
      studied in the presence of three different surfactants, namely the anionic
      surfactant sodium dodecyl sulfate, the nonionic water-soluble surfactant Triton X
      100 and the nonionic, oil-soluble surfactant Span 85. SDS complexation with
      PDMAEMA-grafted nanoparticles was monitored by electrophoretic mobility and
      optical density changes. FINDINGS: Even though SDS is a poor emulsifier,
      emulsification was promoted by SDS at low concentrations, where complexation with
      PDMAEMA-grafted particles produced a synergistic effect on emulsification
      efficiency. Increasing the SDS concentration did not enhance emulsification, and
      stable emulsions formed in the absence of SDS were broken by its addition. The
      enhancement of emulsification efficiency with dilute SDS correlated with low
      degrees of complexation with PDMAEMA such that the nanoparticle-grafted brush had
      a lower charge density and more of an amphiphilic nature. The hindrance of
      emulsification at higher SDS concentrations was attributed to more extensive
      complexation and the resulting brush charge reversal that would inhibit
      adsorption at the oil/water interface in the presence of adsorbing SDS. Synergism
      was also observed in the presence of Triton X-100, while Span 85 had no
      discernible effect on emulsification efficiency, although it is noted that only a
      single concentration of the latter surfactant was investigated.

PMID- 25591824
TI  - Synthesis of gold nanoparticles using various amino acids.
AB  - Gold nanoparticles (4-7nm) were synthesized from tetraauric acid using various
      amino acids as reducing and capping agents. The gold nanoparticles were produced
      from the incubation of a AuCl4(-) solution with an amino acid at 80 degrees C for
      20min. Among the twenty amino acids tested, several amino acids produced gold
      nanoparticles. The color of the nanoparticle solutions varied with the amino
      acids used for the reduction. We adopted l-histidine as a reducing agent and
      investigated the effects of the synthesis conditions on the gold nanoparticles.
      The His and AuCl4(-) concentrations affected the size of the gold nanoparticles
      and their aggregates. The pH of the reaction solution also affected the reaction
      yields and the shape of the gold nanoparticles. 

PMID- 25591825
TI  - A generalized method toward high dispersion of transition metals in large pore
      mesoporous metal oxide/silica hybrids.
AB  - A series of transition metal acetylacetonates and acetates were used as
      precursors to generate high loadings of metal sites finely dispersed on SBA-15
      silica. To achieve this, grafting of chelated transition metal precursors was
      performed directly to the surface of the as-synthesized SBA-15/P123 composite
      material. The thus-obtained metal/SBA-15 materials were studied by a variety of
      methods, e.g., elemental analysis, Fourier transform infrared spectroscopy
      (FTIR), powder X-ray diffraction (XRD), scanning electron microscopy (SEM),
      diffuse reflectance UV-visible spectroscopy (DR-UV-vis), X-ray photoelectron
      spectroscopy (XPS) and N2 physisorption measurements at -196  degrees C. From the
      results, the proposed functionalization method was found to be a highly tunable
      and reproducible strategy to disperse transition metal oxides in mesoporous
      silica materials. The results from elemental analysis of the modified materials
      confirmed that the amount of grafted species is a function of the initial
      concentration of precursor in the solution used for grafting. The chelated
      complexes were found to strongly interact with the silanol groups of the silica
      material, resulting in a ligand-exchange process, as corroborated by FTIR.
      However, different metal precursors showed distinct reactivity towards the
      surface of mesoporous silica, owing to differences in the stability of the
      complexes under the conditions used for grafting. DR-UV-vis and XPS analyses
      suggest that when the stability of a given precursor decreases, the grafting
      procedure can lead to the formation of small clusters of the metal oxide on the
      silica surface. XRD and SEM also show that grafting of lower stability complexes,
      such as Mn(acac)3, Cu(acetate)2 and VO(acac)2, on the silica surface can result
      in the formation of large crystals on the external surface of the SBA-15
      particles. Nevertheless, it was established by XPS analysis that only a small
      percentage of the grafted species leads to the formation of bulk crystals while
      the remaining species are substituted into the silica framework. Obviously, a
      well-controlled and increased dispersion of the metal cations/oxides on the
      surface of highly porous silica materials is of great interest since these
      M(x)O(y)-SiO2 mixed oxides could demonstrate high catalytic activity in a large
      variety of reactions.

PMID- 25591826
TI  - The role of the PI3K pathway in colorectal cancer.
AB  - In the last decade treatment for colorectal cancer (CRC) has evolved with the
      addition of contemporary chemotherapy drugs and targeted therapies. Despite this
      progress, our drug armamentarium is by no means complete and modern molecular
      biology techniques have led to the identification of a number of 'druggable'
      targets. One of the most important current drug targets is the phosphatidyl
      inositol 3-kinase (PI3K) pathway, which is frequently deregulated in patients
      with CRC. In vitro and in vivo data strongly support the clinical development of
      compounds affecting signal transduction via the PI3K pathway. In this review we
      outline the role of PI3K in the development and progression of CRC and discuss
      data from current and ongoing clinical trials targeting this pathway. In addition
      we make suggestions toward the optimization of future research in order to derive
      the maximum benefit for patients with CRC. 

PMID- 25591827
TI  - Evidence against a role of P-glycoprotein in the clearance of the Alzheimer's
      disease Abeta1-42 peptides.
AB  - It has been proposed that the amyloid-beta peptides (Abeta) cause the neuronal
      degeneration in the Alzheimer's disease brain. An imbalance between peptide
      production at the neuronal level and their elimination across the blood-brain
      barrier (BBB) results in peptide accumulation inside the brain. The
      identification and functional characterization of the transport systems in the
      BBB with the capacity to transport Abeta is crucial for the understanding of
      Abeta peptide traffic from the brain to the blood. In this context, it has been
      suggested that the P-glycoprotein (P-gp), expressed in endothelial cells of the
      BBB, plays a role in the elimination of Abeta. However, there is little, if any,
      experimental evidence to support this; therefore, the aim of this investigation
      was to determine whether P-gp is capable of transporting Abeta peptides. Our
      results show that ATPase activity measured in plasma membrane vesicles of K562
      cells overexpressing P-gp is not increased by the presence of Abeta42, suggesting
      that Abeta42 is not a P-gp substrate. Similarly, P-gp of pirarubicin was
      unaffected by Abeta42. Moreover, the overexpression of P-gp does not protect
      cells against Abeta42 toxicity. Taken together, our results support the
      conclusion that Abeta42 is not transported by P-gp. 

PMID- 25591828
TI  - Current status of management of malignant disease: current management of gastric
      cancer.
AB  - Despite a continually decreasing incidence trend, gastric cancer remains a high
      risk malignancy. Symptoms are often unspecific, and upper gastrointestinal
      endoscopy is the key modality for diagnosing early and intermediate-stage
      disease. Surgeons play a critical role in guiding and managing multiple aspects
      of gastric cancer diagnosis and care. Potentially curable gastric adenocarcinoma
      has to be free of distant metastasis and should be staged through endoscopic
      ultrasound and computed tomography. Early (T1N0) gastric cancer can be considered
      for endosopic mucosal resection or submucosal dissection. All other M0 stage
      groups should be evaluated for preoperative chemotherapy or chemoradiation
      followed by resection through a multidisciplinary approach. Laparoscopic staging,
      complete (R0) resection, and extended lymphadenectomy (D2 dissection) are
      critical operative components that optimize curability during gastrectomy. The
      morbidity potential after gastrectomy remains high; splenectomy and distal
      pancreatectomy should be avoided if possible to minimize postoperative
      complications. Laparoscopic gastric cancer resections are increasingly pursued
      and have not shown disadvantages to open gastrectomy as long as oncologic
      principles are followed. For the palliation of specific symptoms in patients with
      incurable gastric cancer, operative interventions should be applied selectively
      if less invasive modalities are insufficient and only if a meaningful benefit can
      be expected from a resection or bypass procedure. Prophylactic total gastrectomy
      should be considered for individuals at risk for hereditary diffuse-type gastric
      cancer through germline E-cadherin gene mutations. Surgeons engaging in gastric
      cancer care are expected to provide specialty expertise in order to plan and
      deliver appropriate care, minimize postoperative morbidity, and optimize
      resulting survival. 

PMID- 25591829
TI  - Bilateral coherence between motor cortices and subthalamic nuclei in patients
      with Parkinson's disease.
AB  - OBJECTIVE: It has been suggested that abnormal synchronization and oscillation of
      neuronal activity in the subthalamic nucleus (STN) is associated with
      sensorimotor dysfunction in Parkinson's disease (PD). We investigated the
      bilateral subcortico-cortical functional coupling in PD patients. METHODS: We
      simultaneously recorded local field potentials from the bilateral STN using
      electrodes inserted for deep brain stimulation and electroencephalograms from the
      bilateral motor cortices (MCx) in 11 patients at rest, and analyzed their
      coherences and causalities. RESULTS: Significant coherence in the sub-beta and
      beta frequency bands was simultaneously observed between the STN and
      contralateral STN (STN-cSTN), the STN and ipsilateral MCx (STN-iMCx), and the STN
      and contralateral MCx (STN-cMCx). In each patient, the frequency of the peak STN
      cSTN coherence was similar to that of the peak STN-iMCx and STN-cMCx coherence.
      The causality between the STN and MCx was strongest in the one-way direction from
      the MCx to the ipsilateral STN. CONCLUSIONS: Abnormal oscillations in the STN in
      the sub-beta and beta bands were functionally coupled among bilateral STN and MCx
      at the eigen-frequency in individual patients with PD. SIGNIFICANCE: Synchronized
      activity through cortico-subcortical transmission may have an important role in
      the pathophysiology of PD.

PMID- 25591830
TI  - Effects of low frequency filtering on distal compound muscle action potential
      duration for diagnosis of CIDP: A Japanese-European multicenter prospective
      study.
AB  - OBJECTIVE: The duration of the distal compound muscle action potential (DCMAP) is
      a useful index to detect demyelination in the distal nerve segments. However in
      published electrodiagnostic criteria for chronic inflammatory demyelinating
      polyneuropathy (CIDP), the cut-off values of DCMAP duration are defined using an
      EMG low frequency filter of only 20 Hz. We aimed to provide widely-available
      reference data using several low cut filters. METHODS: In 13 Japanese and
      European tertiary centers, DCMAP duration data using 2, 5, 10, and 20 Hz low
      frequency filters were prospectively collected from 147 normal controls, 59
      patients with typical CIDP, and 100 with diabetic polyneuropathy. Optimal cut-off
      values were calculated with receiver-operating characteristic curves, offering
      100% specificity versus normal controls. RESULTS: The higher low frequency filter
      was associated with significantly shorter DCMAP duration in all groups. For CIDP
      diagnosis, the calculated cut-off values had a sensitivity ranging from 51% to
      66%, and a specificity versus diabetic neuropathy from 96% to 98%. CONCLUSIONS:
      Our results show that DCMAP duration is largely dependent on low frequency filter
      settings, but is a useful index for CIDP diagnosis when the cut-off values are
      properly determined at each filter setting. SIGNIFICANCE: Our data provide the
      systematic reference values of DCMAP duration for CIDP diagnosis available for
      most EMG laboratories.

PMID- 25591831
TI  - Mechanistic target of rapamycin (mTOR) in tuberous sclerosis complex-associated
      epilepsy.
AB  - BACKGROUND: Tuberous sclerosis complex is a multiorgan disease resulting from a
      mutation of one of two TSC genes. The two gene products form a functional complex
      that regulates the mTOR signaling pathway (mTOR initially represented mammalian
      target of rapamycin, but increasingly the term mechanistic target of rapamycin is
      used to reflect the ubiquitous occurrence of mTOR). Epilepsy is the most common
      neurological symptom of tuberous sclerosis complex, occurring in 80% to 90% of
      affected individuals over the course of their lifetimes and causing significant
      morbidity and mortality. The mechanistic target of rapamycin (mTOR) signaling
      pathway is intricately involved in multiple cellular functions--including protein
      synthesis, cell growth and proliferation, and synaptic plasticity--which may
      influence neuronal excitability and precipitate epileptogenesis. Recent
      preclinical and clinical studies have increased interest in the potential role of
      mTOR inhibitors for the treatment of tuberous sclerosis complex-related epilepsy.
      METHODS: Medline and PubMed database searches were used to identify relevant
      studies and other information on tuberous sclerosis complex-related epilepsies,
      the mTOR pathway, and current advances in treatment approaches. RESULTS: Although
      current management strategies that provide symptomatic relief are effective at
      reducing the frequency of seizures in individuals with tuberous sclerosis
      complex, there is further room for the exploration of therapies that directly
      address hyperactive mTOR signaling--the underlying etiology of the disease. The
      role of the antiepileptic effect of mTOR inhibition was first demonstrated in
      knockout TSC1 mouse models. Additionally, several case studies demonstrated a
      positive effect on seizure frequency and severity in patients with
      pharmacoresistant epilepsy. In a phase 1/2 clinical trial with 28 patients,
      clinically relevant reduction in overall seizure frequency was documented in
      individuals treated with the mTOR inhibitor everolimus. In a phase 3 trial
      evaluating the role of everolimus in subependymal giant cell astrocytoma,
      seizures were a secondary end point. Because the median seizure frequency was
      zero in this study, the analysis was inconclusive. CONCLUSION: Various
      preclinical models provide substantial evidence for the role of mTOR inhibition
      in the treatment of epilepsy in individuals with tuberous sclerosis complex.
      Preliminary clinical studies provide supportive evidence for a role of mTOR
      inhibition in the management of tuberous sclerosis complex-associated epilepsy
      and pave the way for new randomized placebo-controlled studies. This article
      reviews current treatment recommendations for the management of tuberous
      sclerosis complex-associated epilepsy as well as the rationale and evidence to
      support the use of mTOR inhibitors.

PMID- 25591832
TI  - Identification of HIBCH gene mutations causing autosomal recessive Leigh
      syndrome: a gene involved in valine metabolism.
AB  - BACKGROUND: Leigh syndrome is a progressive neurodegenerative disorder with usual
      onset of symptoms during the first year of life. The disorder has been associated
      with mutations in over 30 genes. This difficulty with genetic heterogeneity makes
      whole exome sequencing a more cost-effective approach for investigation of
      etiology. PATIENT AND RESULTS: We describe an individual with typical Leigh
      syndrome who was found to have compound heterozygous mutations in the gene HIBCH
      (3-hydroxyisobutyryl coenzyme A hydrolase), an enzyme involved in the catabolism
      of valine. She exhibited significant clinical improvement after a valine
      restricted diet. CONCLUSIONS: A subset of patients with uncharacterized Leigh
      syndrome present with specific biochemical abnormalities. This report highpoints
      the challenges and restrictions of routine metabolic testing and features the
      recognition of inborn errors of metabolism as potential treatable causes of Leigh
      syndrome.

PMID- 25591833
TI  - Repurposing drugs in your medicine cabinet: untapped opportunities for cancer
      therapy?

PMID- 25591834
TI  - RNA interference in the clinics: where are we standing now?

PMID- 25591835
TI  - Focus on maintenance therapy in non-small-cell lung cancer.

PMID- 25591837
TI  - Bevacizumab with chemotherapy in patients with KRAS wild-type metastatic
      colorectal cancer: Czech registry data.
AB  - AIM: This retrospective analysis investigated the effectiveness of combination
      therapy with bevacizumab and chemotherapy in the first-line treatment of patients
      with KRAS wild-type metastatic colorectal cancer. PATIENTS & METHODS: Patients
      with KRAS wild-type metastatic colorectal cancer in the CORECT registry who
      initiated treatment with bevacizumab between 2008 and 2012 were enrolled. Overall
      survival and progression-free survival were the main effectiveness end points.
      RESULTS: A total of 981 patients were enrolled. Median progression-free survival
      was 11.3 months (95% CI: 10.7-11.8) and median overall survival was 28.4 months
      (95% CI: 26.2-30.6). The most common adverse events were thromboembolic disease
      (4%) and hypertension (3.5%). CONCLUSION: This retrospective analysis shows the
      effectiveness of bevacizumab with chemotherapy in patients with KRAS wild-type
      metastatic colorectal cancer.

PMID- 25591838
TI  - Primary breast cancer in the elderly: a systematic literature review on
      histological type and clinical outcome.
AB  - The objective was to determine whether histological types of breast cancer in
      elderly women influence clinical outcome. Four major databases were searched. All
      relevant articles, from January 1990 to December 2013, were screened. After
      applying inclusion and exclusion criteria, 11 studies were included. Invasive
      ductal carcinoma was the commonest (68.5-87.1%) histological type, followed by
      lobular carcinoma (6.9-17.7%). Four studies reported on survival. However, none
      specifically looked at survival according to different histological types. There
      are very little data on the influence of histological type on clinical outcome in
      primary breast cancer in elderly patients. Further studies may elucidate any
      potential influence and its relationship with tumor biology.

PMID- 25591836
TI  - Does patient education work in breast cancer? Final results from the global
      CARIATIDE study.
AB  - AIM: To determine the impact of educational materials (EMs) on the treatment
      compliance of postmenopausal women with hormone receptor-positive (HR+) early
      stage breast cancer. PATIENTS & METHODS: Patients (n = 2757) were randomized to
      standard aromatase inhibitors (AI) alone (group A) or with EMs (group B) in a
      global, real-world setting. RESULTS: The 2-year results (n = 2242) showed EMs had
      no impact on compliance (82 vs. 82%, group A vs. B), compliance with initial AI
      (82 vs. 81%) or persistence (90 vs. 88%), confirming the 1-year interim analysis
      (n = 2567). Of the 2082 patients considered compliant at 1 year, 77% remained
      compliant at 2 years. Discontinuations (9%) were mainly attributed to AI-related
      side effects (68% of discontinuations). Exploratory analyses suggest a
      relationship between patient characteristics and compliance behaviors.
      CONCLUSION: EMs do not improve compliance in this patient population. Compliance
      and persistence are complex end points influenced by multiple variables. Side
      effects were the main reasons for discontinuations.

PMID- 25591839
TI  - Evolution of targeted therapies in cancer: opportunities and challenges in the
      clinic.
AB  - Targeted therapies have changed the course of cancer treatment in recent years.
      By reducing toxicity and improving outcome, these new generations of precision
      medicines have extended patient lives beyond what could be achieved by the use of
      nontargeted therapies. In the last 2 years, several new molecular entities
      targeting signaling proteins and immune pathways have gone through successful
      clinical development resulting in their approval. These new targeted therapies
      require patient selection and the discovery of biomarkers of response. This
      review discusses the evolution of targeted therapies in cancer and challenges in
      translating the concepts into clinical practice.

PMID- 25591840
TI  - Environmental (nongenetic) factors in gynecological cancers: update and future
      perspectives.
AB  - Globally, gynecological cancers comprise three of the seven most common female
      cancers and are responsible for more than 1,000,000 new cases and 500,000 deaths
      annually. This review summarizes current knowledge regarding the role of
      environmental factors in gynecological cancer etiology and survival, focusing on
      those that are potentially amenable to intervention. Strong associations with use
      of exogenous hormones are countered by opposing risks of breast cancer, thus
      current hormonal preparations are not an option for prevention. Weight control
      would reduce risk of endometrial cancer but this and other lifestyle
      modifications are unlikely to have a major effect on gynecological cancer
      mortality rates. There is little information regarding the potential for
      lifestyle changes to improve outcomes for women with gynecological cancer.

PMID- 25591841
TI  - Para-aortic nodal metastases in cervical cancer: a blind spot in the
      International Federation of Gynecology and Obstetrics staging system: current
      diagnosis and management.
AB  - In cervical cancer, para-aortic nodal (PALN) metastases at presentation is a
      strong indicator of poor prognosis. Despite this, International Federation of
      Gynecology and Obstetrics staging system does not require evaluation of lymph
      node involvement and does not incorporate clinically detected PALN into the
      staging system. In the USA, despite screening, a significant number of women
      still present at an advanced stage often with nodal metastases. While the
      presence of PALN metastases often indicates occult systemic disease, it is
      possible with modern therapies to provide long-term control of disease in a
      percentage of patients. We review the epidemiology, diagnosis and treatment of
      PALN metastases in cervical cancer outlining advances in modern imaging and
      combined modality therapies (surgery, chemotherapy and radiation therapy).

PMID- 25591842
TI  - Epigenetic alterations in cancer and personalized cancer treatment.
AB  - Based on the pivotal importance of epigenetics for transcription regulation, it
      is not surprising that cancer is characterized by several epigenetic
      abnormalities. Conversely to genetic alterations, epigenetic changes are not
      permanent, thus represent opportunities for therapeutic strategies designed to
      reverse transcriptional abnormalities, and cancer is the first disease in which
      epigenetic therapies with chromatin remodeling agents were introduced. The role
      of miRNAs in gene regulation supports their potential as innovative therapeutic
      strategy. Recent evidences have proven that the environment can profoundly
      influence the epigenome: diet, smoking and alcohol consumption can negatively
      impact the expression profile. Given the plasticity of epigenetic marks, it is
      challenging the idea that the epigenetic alterations are 'druggable' sites using
      specific food components.

PMID- 25591843
TI  - miR-214: a potential biomarker and therapeutic for different cancers.
AB  - miRNAs (miRs), or small approximately 22-nucleotide-long single-stranded
      noncoding RNA molecules, interact with 3' untranslated regions of target mRNAs,
      leading to inhibition of protein production. miR-214 is often dysregulated in
      various cancers, which governs both tumorigenic and tumor suppressive functions.
      This review focuses on the current knowledge of miR-214 switching in diverse
      forms of cancer either by its upregulation or downregulation and sheds light on
      the mechanism of its tumorigenic and suppressive roles. This article describes
      known targets and signaling pathways that impact tumorigenesis and tumor
      suppression and summarizes all information available on circulating levels of miR
      214 to address whether miR-214 may function as a potential biomarker and therapy
      for cancer patients in the future.

PMID- 25591844
TI  - Diagnosis and management of congenital hypothyroidism associated with
      pseudohypoparathyroidism.
AB  - Hypothyroidism is a particular condition observed in pseudohypoparathyroidism
      (PHP), a rare disorder characterized by parathyroid (PTH) resistance leading to
      hypocalcemia and hyperphosphatemia associated with a GNAS (guanine nucleotide
      binding protein alpha-subunit) mutation (PHP1A) or epimutation (PHP1B). To
      determine the presence of hypothyroidism at birth we conducted a retrospective
      study in our cohort of patients presenting with either PHP1A (n = 116) or PHP1B
      (n = 99). We also investigated patients presenting at birth with congenital
      hypothyroidism (CH) and a eutopic thyroid gland for phosphocalcium abnormalities
      suggesting PTH resistance and PHP. Our study reveals CH as the earliest
      diagnostic clue for PHP1A, but not for PHP1B. We estimated the frequency of CH at
      birth to be between 8 and 34% in patients presenting with PHP1A. The elevation of
      phosphatemia and PTH concentration precedes hypocalcemia in PHP1A. Conversely,
      the frequency of PHP1A in patients presenting CH is dramatically low. This may be
      due to the low prevalence of PHP1A which remains unknown. CONCLUSIONS:
      Subclinical and overt hypothyroidism can occur in PHP1A patients at birth many
      years before PTH resistance becomes clinically apparent. Although such cases
      appear to be rare, some pediatric patients with unexplained CH are likely to
      benefit from measuring calcium, phosphorus, and PTH for extended periods of time.

PMID- 25591845
TI  - Risk factors of indoor fall injuries in community-dwelling older women: a
      prospective cohort study.
AB  - The aims of the study were to explore the characteristics and the potential risk
      factors of indoor fall injuries in community-dwelling older women, and to provide
      evidence for the future intervention strategy. A prospective cohort of 3043 women
      aged 60 years old and above from 3 selected counties in Shanghai was followed up
      on the outcomes of indoor fall injuries for up to 1 year. Demographic and health
      data were collected during admission; the physical function, balance ability and
      home-living environment were examined by a structured questionnaire when
      admitted. The outcome of indoor fall injury was investigated by a visit in month
      3, month 6 and month 12 after baseline survey. Univariate analysis and Multiple
      Logistic Regression Model were used to examine the associations between potential
      risk factors and outcomes of indoor fall injuries. Two hundred and thirty-one of
      the 3043 women (7.6%) eventually suffered indoor fall injuries at least once
      during the 1-year follow-up. The injurious falls of women were significantly
      associated with age, educational level, marital status, health status, balance
      ability, physical activity and home-living environment in the univariate
      analyses. Women who worried about falls and restrained activities for it were
      more likely to suffer fall injury. Younger women, with less chronic disease, with
      good balance ability and living in good corridor environment, were less likely to
      receive fall injury in multiple logistic regression analyses. Multidimensional
      factors were associated with indoor fall injuries for community-dwelling older
      women. Proper clinical treatment of chronic disease and improvement of women's
      balance ability, as well as reducing the risk factor of indoor environment, which
      will play vital roles in preventing indoor fall injuries, should be prioritized
      for the intervention strategy. 

PMID- 25591846
TI  - Host CD8alpha+ dendritic cells may be a key factor for separating graft-versus
      host disease from graft-versus-leukemia.

PMID- 25591847
TI  - Impact of serotherapy on immune reconstitution and survival outcomes after stem
      cell transplantations in children: thymoglobulin versus alemtuzumab.

PMID- 25591849
TI  - X-linked agammaglobulinemia associated with B-precursor acute lymphoblastic
      leukemia.
AB  - X-linked agammaglobulinemia (XLA) is clinically characterized by reduced number
      of peripheral B cells and diminished levels of serum immunoglobulins, and caused
      by a mutation in the Bruton's tyrosine kinase (BTK) gene, which play a pivotal
      role in signal transduction of pre-B-cell receptor (BCR) and BCR. B-cell
      precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in
      children, and it may be associated with gene alterations that regulate B-cell
      development. Here we described a first case of XLA associated BCP-ALL. The whole
      exome sequencing revealed a somatic mutation in MLL2 in the sample from the onset
      of BCP-ALL. This study suggests that the alterations of BTK and MLL2
      synergistically function as leukemogenesis. 

PMID- 25591848
TI  - Bone mineral density in children with fanconi anemia after hematopoietic cell
      transplantation.
AB  - Fanconi anemia (FA) is an inherited DNA repair disorder associated with short
      stature and bone marrow failure, usually requiring hematopoietic cell
      transplantation (HCT). Although low bone mineral density (BMD) has been reported
      in leukemia patients after HCT, little is known about BMD in FA children after
      HCT (FA HCT). This study's goals were to compare BMD in FA HCT to BMD in healthy
      controls and in children who received HCT for hematologic malignancy (cancer
      HCT), and to test for associations between BMD and risk factors for bone loss.
      This cross-sectional study included 20 FA HCT, 13 cancer HCT, and 90 healthy
      controls, age-matched and <18 years old at evaluation. BMD Z-scores for total
      body (TBMD) and lumbar spine (LBMD) were measured by dual energy x-ray
      absorptiometry and adjusted for height-for-age Z-score (HAZ). FA HCT had lower
      mean TBMDHAZ Z-score (by .8 SD) and higher fraction with Z-score <= -1 than
      healthy controls (42% versus 11%). No LBMD deficits were detected. FA HCT and
      cancer HCT groups did not differ significantly in TBMD or LBMD Z-scores. In FA
      HCT patients, lower body mass index and lower percent fat were associated with
      lower BMD. This study highlights the importance of monitoring BMD to optimize
      bone health in FA patients.

PMID- 25591851
TI  - Nanotechnological carriers for cancer chemotherapy: the state of the art.
AB  - Cancer is a term used for a heterogeneous group of malignant diseases in which
      abnormal cells divide without control and are able to invade other tissues,
      resulting in metastasis. According to the last data of World Health Organization
      the incidence and mortality rates of cancer are high and tend to increase.
      Chemotherapy is usually used in cancer treatments, but due to the lack of
      specificity of drugs, is associated to various and damaging side effects that
      have a severe impact on patients quality of life. Nanotechnology is actually an
      important area of interest in science and technology, which has been extensively
      explored during the last decade, particularly in the development of carriers for
      cytotoxic drugs. These carriers include vesicular and particulate systems such as
      liposomes, niosomes, transfersomes, ethosomes, micelles, dendrimers, and
      polymeric, protein and lipid nanoparticles. Polymer-drug conjugates and antibody
      drug conjugates have also been studied. The present review is an attempt to
      contemplate the studied nanocarriers in the field of anticancer drugs delivery,
      their advantages and disadvantages and future perspectives. 

PMID- 25591850
TI  - Multifunctional drug nanocarriers formed by cRGD-conjugated betaCD-PAMAM-PEG for
      targeted cancer therapy.
AB  - Polyamidoamine (PAMAM) dendrimer was conjugated with both carboxymethyl-beta
      cyclodextrin (betaCD) and poly(ethylene glycol) (PEG). Cyclic RGD peptide, used
      as a tumor targeting ligand, was then selectively conjugated onto the distal ends
      of the PEG arms. The resulting betaCD-PAMAM-PEG-cRGD polymer was able to form
      stable and uniform nanoparticles (NPs) in aqueous solution. Doxorubicin (Dox), a
      model hydrophobic anticancer drug, was effectively encapsulated in the NPs via an
      inclusion complex formed between the drug and betaCD. The Dox loading level was
      16.8 wt%. The cellular uptake of cRGD-conjugated Dox-loaded NPs in the U87MG cell
      line was much higher than that of non-targeted NPs. Furthermore, the anti
      proliferative effect of the cRGD-conjugated NPs was superior to that of free drug
      and non-targeted NPs. These results suggest that NPs formed by betaCD-PAMAM-PEG
      cRGD with a high drug payload may significantly improve the anticancer efficacy
      by tumor-targeted delivery and enhanced cellular uptake.

PMID- 25591852
TI  - The degree of autonomic modulation is associated with the severity of
      microvascular complications in patients with type 1 diabetes.
AB  - OBJECTIVE: The objective of this study was to elucidate whether the degree of
      autonomic modulation is associated with the degree of microvascular complications
      in patients with type 1 diabetes. METHODS: A total of 290 type 1 individuals with
      diabetes were randomly recruited during normal visits to outpatient clinics at 4
      Danish hospitals. The degree of autonomic modulations was quantified by measuring
      heart rate variability (HRV) during passive spectral analysis and active tests
      (valsalva ratio [VT], response to standing [RT], and deep breathing [E:I]). To
      describe possible associations between severity of microvascular complications
      and measures of autonomic modulation, multivariate analysis was performed.
      RESULTS: After adjusting for diabetes duration, sex, age, pulse pressure, heart
      rate, and smoking, autonomic dysfunction remained significantly correlated with
      severity of retinopathy, nephropathy, and peripheral neuropathy in individuals
      with type 1 diabetes patients. CONCLUSIONS: Autonomic dysfunction is present in
      early stages of retinopathy, nephropathy, and peripheral neuropathy in patients
      with type 1 diabetes.

PMID- 25591853
TI  - Adherence to glycemic monitoring in diabetes.
AB  - Glucose monitoring either by self-monitoring of blood glucose (SMBG) or
      continuous glucose monitoring (CGM) plays an important role in diabetes
      management and in reducing risk for diabetes-related complications. However,
      despite evidence supporting the role of glucose monitoring in better patient
      health outcomes, studies also reveal relatively poor adherence rates to SMBG and
      CGM use and numerous patient-reported barriers. Fortunately, some promising
      intervention strategies have been identified that promote at least short-term
      improvements in patients' adherence to SMBG. These include education, problem
      solving, contingency management, goal setting, cognitive behavioral therapy, and
      motivational interviewing. Specific to CGM, interventions to promote greater use
      among patients are currently under way, yet one pilot study provides data
      suggesting better maintenance of CGM use in patients showing greater readiness
      for behavior change. The purpose of this review is to summarize the literature
      specific to glucose monitoring in patients with diabetes focusing specifically on
      current adherence rates, barriers to monitoring, and promising intervention
      strategies that may be ready to deploy now in the clinic setting to promote
      greater patient adherence to glucose monitoring. Yet, to continue to help
      patients with diabetes adhere to glucose monitoring, future research is needed to
      identify the treatment strategies and the intervention schedules that most likely
      lead to long-term maintenance of optimal glycemic monitoring levels. 

PMID- 25591854
TI  - Analytical evaluation of the Diazyme glycated serum protein assay on the siemens
      ADVIA 1800: comparison of results against HbA1c for diagnosis and management of
      diabetes.
AB  - Hemoglobin A1c (HbA1c) is considered the gold standard for assessment of glycemic
      control in diabetic patients. HbA1c is inadequate in individuals homozygous or
      compound heterozygous for hemoglobin variants or in conditions with an altered
      red blood cell turnover. In these cases glycated albumin (GA) is proposed as an
      alternative assay. We aimed to evaluate the analytical performance of the Diazyme
      glycated serum protein (GSP) assay on an automated analyzer, to establish a
      reference interval (RI), and to compare from a clinical perspective, GSP/GA with
      glycated Hb (glyHb) results. Validation studies followed the CLSI guidelines and
      included precision, linearity, interferences, concordance of results with glyHb,
      and RI calculation. GSP was analyzed on representative samples with previously
      ordered HbA1c and albumin from the Dyna LIFE : DX laboratory. Samples from
      patients with bisalbuminemia, hemoglobinopathies, and multiple myeloma were also
      included. Within-run and total imprecision was <3.0% at both levels of control,
      analytical sensitivity was 5.31 MUmol/L, and linearity was verified from 10 to
      1150 MUmol/L (total allowable error of 5%). Clinical concordance between %GA and
      glyHb was substantial (n = 175, R2 = .91, kappa = .78, P = .167). GSP RI was 160
      to 340 MUmol/L or if expressed as %GA 10.5 to 17.5%. Analytical performance of
      the Diazyme GSP assay on the Siemens ADVIA 1800 is acceptable for clinical use.
      The RI obtained was higher than that suggested by the manufacturer.

PMID- 25591855
TI  - High reported treatment satisfaction in people with type 1 diabetes switching to
      latest generation insulin pump regardless of previous therapy.
AB  - The effects of transition by individuals with type 1 diabetes (T1D) to more
      recently available continuous glucose monitoring (CGM)-enabled insulin pumps from
      either multiple daily insulin injections (MDI) or older insulin pumps on
      treatment satisfaction have not been well studied. We conducted a survey to
      assess treatment satisfaction among users of the Animas((r)) VibeTM insulin pump,
      a latest generation insulin pump (LGIP) system (CGM-enabled), after switching
      from MDI or earlier generation insulin pumps. Individuals with T1D from 141
      centers in 5 countries and 4 language areas participated in the survey. Treatment
      satisfaction was assessed by the Insulin Treatment Satisfaction Questionnaire
      (ITSQ), which was included in a 50-item online questionnaire that also assessed
      preference for using the LGIP compared with previous treatment and satisfaction
      with key LGIP features. A total of 356 individuals, ages 12-79 years, responded
      to the survey: mean (SD) age 38.4 (16.1) years; diabetes duration 19.1 (13.3)
      years; female 59%; previously treated with MDI 58%. Overall mean (SD) ITSQ scores
      were high among all respondents regardless of prior treatment: 95.1 (23.2)
      (scale: 0-132). No differences between previous-treatment groups were seen. Most
      (83%) of respondents rated the LGIP to be better than their previous insulin
      delivery system: "much better" (65%), "a bit better" (18%) regardless of age, and
      95% would recommend using the LGIP to others. Use of the Animas Vibe was
      associated with high treatment satisfaction and perceived as a better method of
      insulin delivery regardless of previous insulin therapy or age. 

PMID- 25591856
TI  - Advantages and pitfalls of fructosamine and glycated albumin in the diagnosis and
      treatment of diabetes.
AB  - The efficient diagnosis and accurate monitoring of diabetic patients are
      cornerstones for reducing the risk of diabetic complications. The current
      diagnostic and prognostic strategies in diabetes are mainly based on two tests,
      plasma (or capillary) glucose and glycated hemoglobin (HbA1c). Nevertheless,
      these measures are not foolproof, and their clinical usefulness is biased by a
      number of clinical and analytical factors. The introduction of other indices of
      glucose homeostasis in clinical practice such as fructosamine and glycated
      albumin (GA) may be regarded as an attractive alternative, especially in patients
      in whom the measurement of HbA1c may be biased or even unreliable. These include
      patients with rapid changes of glucose homeostasis and larger glycemic
      excursions, and patients with red blood cell disorders and renal disease.
      According to available evidence, the overall diagnostic efficiency of GA seems
      superior to that of fructosamine throughout a broad range of clinical settings.
      The current method for measuring GA is also better standardized and less
      vulnerable to preanalytical variables than those used for assessing fructosamine.
      Additional advantages of GA over HbA1c are represented by lower reagent cost and
      being able to automate the GA analysis on many conventional laboratory
      instruments. Although further studies are needed to definitely establish that GA
      can complement or even replace conventional measures of glycemic control such as
      HbA1c, GA may help the clinical management of patients with diabetes in whom
      HbA1c values might be unreliable. 

PMID- 25591857
TI  - Performance and acceptability of a combined device for insulin infusion and
      glucose sensing in the home setting.
AB  - The use of sensor-augmented insulin pump (SAP) therapy is increasing. Currently,
      glucose sensors and insulin infusion cannulas are inserted separately. A new
      device, MiniMed Duo, combines sensing and infusion capabilities on the same
      platform and is intended to simplify device insertion and site management. We
      evaluated the device's performance with respect to insulin delivery and glucose
      sensing, and its acceptability with patients. Forty-five patients (mean +/- SD
      age, 45.5 +/- 10.9 years, 48% female) with type 1 diabetes and previous use of
      SAP participated. Each subject was to wear 5 devices connected to insulin pumps
      over 15 days (3 days/device) and test capillary blood glucose (SMBG) 7 times/day.
      The primary endpoint was the percentage of sensor-SMBG paired values within 20%
      of one another. Subject experiences were assessed via questionnaires. Overall,
      74.8% of sensor-SMBG paired values were within 20%, meeting the primary accuracy
      endpoint, and the mean absolute relative difference was 15.5 +/- 17.1%. Consensus
      error grid analysis showed that >95% of points were within the A+B zones,
      exceeding the threshold for adequate clinical accuracy. Insulin dosage and SMBG
      values did not change significantly compared to prestudy values. The functional
      survival of the device entering day 3 was 90.5%. There were no serious adverse
      events. Mean questionnaire results indicated overall satisfaction with the
      device. Duo provided insulin infusion and glucose sensing capabilities in a
      single device, which provided accurate glucose readings during routine use, was
      safe to wear, and was acceptable to most patients. It may improve satisfaction
      and convenience for patients using sensor-augmented insulin pumps. 

PMID- 25591858
TI  - A comparison of glide force characteristics between 2 prefilled insulin lispro
      pens.
AB  - Glide force, average glide force, and glide force variability of the insulin
      lispro 200 units/mL pen (Eli Lilly and Company, Indianapolis, IN, USA) were
      compared to the Humalog KwikPen 100 units/mL pen (hereafter, KwikPen; Eli Lilly
      and Company, Indianapolis, IN, USA). Data were collected on 2 doses, 2 injection
      speeds, and 2 needle types. Insulin lispro 200 units/mL pen showed significantly
      lower maximum glide force, average glide force, and glide force variability than
      the KwikPen across all combinations of dose size, dose speed, and needle type.
      The lower glide force observed with the insulin lispro 200 units/mL pen offers
      another treatment option for patients with type 1 or type 2 diabetes who require
      greater than 20 units of mealtime insulin daily.

PMID- 25591859
TI  - Performance of the first combined smartwatch and smartphone diabetes diary
      application study.
AB  - BACKGROUND: Wearable computing has long been described as the solution to many
      health challenges. However, the use of this technology as a diabetes patient self
      management tool has not been fully explored. A promising platform for this use is
      the smartwatch-a wrist-worn device that not only tells time but also provides
      internet connection and ability to communicate information to and from a mobile
      phone. METHOD: Over 9 months, the design of a diabetes diary application for a
      smartwatch was completed using agile development methods. The system, including a
      two-way communication between the applications on the smartwatch and mobile
      phone, was tested with 6 people with type 1 diabetes. A small number of
      participants was deliberately chosen due to ensure an efficient use of resources
      on a novel system. RESULTS: The designed smartwatch system displays the time,
      day, date, and remaining battery time. It also allows for the entry of
      carbohydrates, insulin, and blood glucose (BG), with the option to view
      previously recorded data. Users were able to record specific physical activities,
      program reminders, and automatically record and transfer data, including step
      counts, to the mobile phone version of the diabetes diary. The smartwatch system
      can also be used as a stand-alone tool. Users reported usefulness, responded
      positively toward its functionalities, and also provided specific suggestions for
      further development. Suggestions were implemented after the feasibility study.
      CONCLUSIONS: The presented system and study demonstrate that smartwatches have
      opened up new possibilities within the diabetes self-management field by
      providing easier ways of monitoring BG, insulin injections, physical activity and
      dietary information directly from the wrist.

PMID- 25591860
TI  - Bifidobacteria strains isolated from stools of iron deficient infants can
      efficiently sequester iron.
AB  - BACKGROUND: Bifidobacteria is one of the major gut commensal groups found in
      infants. Their colonization is commonly associated with beneficial effects to the
      host through mechanisms like niche occupation and nutrient competition against
      pathogenic bacteria. Iron is an essential element necessary for most
      microorganisms, including bifidobacteria and efficient competition for this
      micronutrient is linked to proliferation and persistence. For this research we
      hypothesized that bifidobacteria in the gut of iron deficient infants can
      efficiently sequester iron. The aim of the present study was to isolate
      bifidobacteria in fecal samples of iron deficient Kenyan infants and to
      characterize siderophore production and iron internalization capacity. RESULTS:
      Fifty-six bifidobacterial strains were isolated by streaking twenty-eight stool
      samples from Kenyan infants, in enrichment media. To target strains with high
      iron sequestration mechanisms, a strong iron chelator 2,2-dipyridyl was
      supplemented to the agar media. Bifidobacterial isolates were first identified to
      species level by 16S rRNA sequencing, yielding B. bifidum (19 isolates), B.
      longum (15), B. breve (11), B. kashiwanohense (7), B. pseudolongum (3) and B.
      pseudocatenulatum (1). While most isolated bifidobacterial species are commonly
      encountered in the infantile gut, B. kashiwanohense was not frequently reported
      in infant feces. Thirty strains from culture collections and 56 isolates were
      characterized for their siderophore production, tested by the CAS assay.
      Siderophore activity ranged from 3 to 89% siderophore units, with 35 strains
      (41%) exhibiting high siderophore activity, and 31 (36%) and 20 (23%) showing
      intermediate or low activity. The amount of internalized iron of 60
      bifidobacteria strains selected for their siderophore activity, was in a broad
      range from 8 to118 MUM Fe. Four strains, B. pseudolongum PV8-2, B. kashiwanohense
      PV20-2, B. bifidum PV28-2a and B. longum PV5-1 isolated from infant stool samples
      were selected for both high siderophore activity and iron internalization.
      CONCLUSIONS: A broad diversity of bifidobacteria were isolated in infant stools
      using iron limited conditions, with some strains exhibiting high iron
      sequestration properties. The ability of bifidobacteria to efficiently utilize
      iron sequestration mechanism such as siderophore production and iron
      internalization may confer an ecological advantage and be the basis for enhanced
      competition against enteropathogens.

PMID- 25591861
TI  - Functional and mechanistic investigation of Shikonin in scarring.
AB  - Scarring is a significant medical burden; financially to the health care system
      and physically and psychologically for patients. Importantly, there have been
      numerous case reports describing the occurrence of cancer in burn scars.
      Currently available therapies are not satisfactory due to their undesirable side
      effects, complex delivery routes, requirements for long-term use and/or expense.
      Radix Arnebiae (Zi Cao), a perennial herb, has been clinically applied to treat
      burns and manage scars for thousands of years in Asia. Shikonin, an active
      component extracted from Radix Arnebiae, has been demonstrated to induce
      apoptosis in cancer cells. Apoptosis is an essential process during scar tissue
      remodelling. It was therefore hypothesized that Shikonin may induce apoptosis in
      scar-associated cells. This investigation presents the first detailed in vitro
      study examining the functional responses of scar-associated cells to Shikonin,
      and investigates the mechanisms underlying these responses. The data obtained
      suggests that Shikonin inhibits cell viability and proliferation and reduces
      detectable collagen in scar-derived fibroblasts. Further investigation revealed
      that Shikonin induces apoptosis in scar fibroblasts by differentially regulating
      the expression of caspase 3, Bcl-2, phospho-Erk1/2 and phospho-p38. In addition,
      Shikonin down-regulates the expression of collagen I, collagen III and alpha
      smooth muscle actin genes hence attenuating collagen synthesis in scar-derived
      fibroblasts. In summary, it is demonstrated that Shikonin induces apoptosis and
      decreases collagen production in scar-associated fibroblasts and may therefore
      hold potential as a novel scar remediation therapy. 

PMID- 25591862
TI  - ApoA-IV: current and emerging roles in intestinal lipid metabolism, glucose
      homeostasis, and satiety.
AB  - Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine on chylomicrons
      into intestinal lymph in response to fat absorption. Many physiological functions
      have been ascribed to apoA-IV, including a role in chylomicron assembly and lipid
      metabolism, a mediator of reverse-cholesterol transport, an acute satiety factor,
      a regulator of gastric function, and, finally, a modulator of blood glucose
      homeostasis. The purpose of this review is to update our current view of
      intestinal apoA-IV synthesis and secretion and the physiological roles of apoA-IV
      in lipid metabolism and energy homeostasis, and to underscore the potential for
      intestinal apoA-IV to serve as a therapeutic target for the treatment of diabetes
      and obesity-related disease. 

PMID- 25591864
TI  - The role of K+ conductances in regulating membrane excitability in human gastric
      corpus smooth muscle.
AB  - Changes in resting membrane potential (RMP) regulate membrane excitability. K(+)
      conductance(s) are one of the main factors in regulating RMP. The functional role
      of K(+) conductances has not been studied the in human gastric corpus smooth
      muscles (HGCS). To examine the role of K(+) channels in regulation of RMP in HGCS
      we employed microelectrode recordings, patch-clamp, and molecular approaches.
      Tetraethylammonium and charybdotoxin did not affect the RMP, suggesting that BK
      channels are not involved in regulating RMP. Apamin, a selective small
      conductance Ca(2+)-activated K(+) channel (SK) blocker, did not show a
      significant effect on the membrane excitability. 4-Aminopyridine, a Kv channel
      blocker, caused depolarization and increased the duration of slow wave
      potentials. 4-Aminopyridine also inhibited a delayed rectifying K(+) current in
      isolated smooth muscle cells. End-product RT-PCR gel detected Kv1.2 and Kv1.5 in
      human gastric corpus muscles. Glibenclamide, an ATP-sensitive K(+) channel (KATP)
      blocker, did not induce depolarization, but nicorandil, a KATP opener,
      hyperpolarized HGCS, suggesting that KATP are expressed but not basally
      activated. Kir6.2 transcript, a pore-forming subunit of KATP was expressed in
      HGCS. A low concentration of Ba(2+), a Kir blocker, induced strong
      depolarization. Interestingly, Ba(2+)-sensitive currents were minimally expressed
      in isolated smooth muscle cells under whole-cell patch configuration. KCNJ2
      (Kir2.1) transcript was expressed in HGCS. Unique K(+) conductances regulate the
      RMP in HGCS. Delayed and inwardly rectifying K(+) channels are the main
      candidates in regulating membrane excitability in HGCS. With the development of
      cell dispersion techniques of interstitial cells, the cell-specific functional
      significance will require further analysis.

PMID- 25591863
TI  - Animal models of gastrointestinal and liver diseases. Animal models of cystic
      fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and
      pathophysiology.
AB  - Multiple organ systems, including the gastrointestinal tract, pancreas, and
      hepatobiliary systems, are affected by cystic fibrosis (CF). Many of these
      changes begin early in life and are difficult to study in young CF patients.
      Recent development of novel CF animal models has expanded opportunities in the
      field to better understand CF pathogenesis and evaluate traditional and
      innovative therapeutics. In this review, we discuss manifestations of CF disease
      in gastrointestinal, pancreatic, and hepatobiliary systems of humans and animal
      models. We also compare the similarities and limitations of animal models and
      discuss future directions for modeling CF. 

PMID- 25591865
TI  - Effects of obesity on severity of colitis and cytokine expression in mouse
      mesenteric fat. Potential role of adiponectin receptor 1.
AB  - In inflammatory bowel disease (IBD), obesity is associated with worsening of the
      course of disease. Here, we examined the role of obesity in the development of
      colitis and studied mesenteric fat-epithelial cell interactions in patients with
      IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid
      (TNBS) colitis mouse model to create groups with obesity, colitis, and their
      combination. Changes in the mesenteric fat and intestine were assessed by
      histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR.
      Medium from human mesenteric fat and cultured preadipocytes was obtained from
      obese patients and those with IBD. Histological analysis showed inflammatory cell
      infiltrate and increased histological damage in the intestine and mesenteric fat
      of obese mice with colitis compared with all other groups. Obesity also increased
      the expression of proinflammatory cytokines including IL-1beta, TNF-alpha,
      monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it
      decreased the TNBS-induced increases in IL-2 and IFN-gamma in mesenteric adipose
      and intestinal tissues. Human mesenteric fat isolated from obese patients and
      those with and IBD demonstrated differential release of adipokines and growth
      factors compared with controls. Fat-conditioned media reduced adiponectin
      receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1
      intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion,
      obesity worsens the outcome of experimental colitis, and obesity- and IBD
      associated changes in adipose tissue promote differential mediator release in
      mesenteric fat that modulates colonocyte responses and may affect the course of
      colitis. Our results also suggest an important role for AdipoR1 for the fat
      intestinal axis in the regulation of inflammation during colitis. 

PMID- 25591867
TI  - Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber
      subtypes in guinea pig esophagus.
AB  - Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel,
      which selectively expresses in primary sensory afferent nerve, and is essential
      in mediating inflammatory nociception. Our previous study demonstrated that TRPA1
      plays an important role in tissue mast cell activation-induced increase in the
      excitability of esophageal vagal nodose C fibers. The present study aims to
      determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea
      pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses
      in esophageal mucosa were first assessed by histological stains and Ussing
      chamber studies. TRPA1 function in vagal sensory neurons was then studied by
      calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal
      nodose and jugular neurons. Extracellular single-unit recordings were performed
      in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal
      vagal preparations with intact nerve endings in the esophagus. Antigen challenge
      significantly increased infiltrations of eosinophils and mast cells in the
      esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in
      nodose and jugular neurons was significantly increased, and current densities in
      esophageal DiI-labeled nodose and jugular neurons were also significantly
      increased in antigen-challenged animals. Prolonged antigen challenge decreased
      esophageal epithelial barrier resistance, which allowed intraesophageal-infused
      AITC-activating nodose and jugular C fibers at their nerve endings. Collectively,
      these results demonstrated that prolonged antigen challenge sensitized TRPA1 in
      esophageal sensory neurons and afferent C fibers. This novel finding will help us
      to better understand the molecular mechanism underlying esophageal sensory and
      motor dysfunctions in EoE. 

PMID- 25591866
TI  - TRPM8 function and expression in vagal sensory neurons and afferent nerves
      innervating guinea pig esophagus.
AB  - Sensory transduction in esophageal afferents requires specific ion channels and
      receptors. TRPM8 is a new member of the transient receptor potential (TRP)
      channel family and participates in cold- and menthol-induced sensory
      transduction, but its role in visceral sensory transduction is still less clear.
      This study aims to determine TRPM8 function and expression in esophageal vagal
      afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in
      nodose and jugular neurons by calcium imaging and then investigated by whole cell
      patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons.
      Extracellular single-unit recordings were performed in nodose and jugular C fiber
      neurons using ex vivo esophageal-vagal preparations with intact nerve endings in
      the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in
      Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12
      elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS
      12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but
      not nodose neurons in a dose-dependent manner, which could be inhibited by the
      TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in
      esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were
      highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In
      summary, the present study demonstrated a preferential expression and function of
      TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes.
      This provides a distinctive role of TRPM8 in esophageal sensory transduction and
      may lead to a better understanding of the mechanisms of esophageal sensation and
      nociception. 

PMID- 25591868
TI  - A case of acute kidney injury from crystal nephropathy secondary to pomalidomide
      and levofloxacin use.
AB  - Pomalidomide is an analog of thalidomide with immunomodulatory, anti-angiogenic,
      and anti-neoplastic activity indicated for the treatment of multiple myeloma
      refractory to at least two prior therapies. The incidence for renal failure was
      <5% in a single phase II study of pomalidomide and dexamethasone in patients with
      multiple myeloma that failed both lenalidomide and bortezomib therapy. We report
      a case suggesting crystal nephropathy as the mechanism for acute kidney injury in
      pomalidomide and fluoroquinolone use. 

PMID- 25591869
TI  - Secondary thrombotic microangiopathy in two patients with Philadelphia-positive
      hematological malignancies treated with imatinib mesylate.
AB  - Drug-mediated thrombotic microangiopathy may cause life-threatening medical
      emergencies. Novel targeted therapies have dramatically changed the prognosis of
      a number of oncological diseases. Tyrosine kinase inhibitors of the Breakpoint
      Cluster Region-Abelson (BCR-ABL) oncoprotein are used in patients with chronic
      myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic
      leukemia. Imatinib mesylate, which was the first anti-BCR-ABL tyrosine kinase
      inhibitor, has demonstrated a high tolerance profile and efficacy in these
      patients for many years. Good results have also been observed in patients with
      gastrointestinal stromal tumors. In this study, we describe two patients with
      Philadelphia chromosome-positive hematological malignancies who presented with
      secondary thrombotic microangiopathy that was most likely linked to the use of
      imatinib. Other potential causes of thrombotic microangiopathy were discarded,
      and the predisposing role of some comorbidities and potential short or long-term
      drug-drug interactions was assessed. The clinical and biological data were more
      indicative of atypical secondary hemolytic uremic syndrome in one of the cases
      and of secondary thrombotic microangiopathy with renal and cardiac impairment in
      the other, which is also categorized as secondary hemolytic uremic syndrome. The
      outcome was favorable after imatinib discontinuation and the treatment of severe
      cardiac and renal failures. 

PMID- 25591870
TI  - [Liver diseases and pregnancy].
AB  - Liver disease can be observed in pregnant women whether or not related to
      pregnancy. Liver disorders can be revealed by pruritus, vomiting, jaundice or
      abnormal liver blood tests during pregnancy. These liver manifestations can lead
      to the diagnosis of liver disease specifically associated to pregnancy as
      intrahepatic pregnancy, intrahepatic cholestasis of pregnancy, Hyperemesis
      gravidarum, acute fatty liver of pregnancy and preeclampsia-induced liver injury.
      Pregnancy may also be a risk factor for other liver diseases coincident with
      pregnancy as viral hepatitis, thrombosis, drug toxicity or gallstone. Finally,
      pre-existing liver disease must be taken into account given the risk of foeto
      maternal transmission risk as well as the risk of decompensation of underlying
      cirrhosis secondary to the hemodynamic changes caused by pregnancy. The aim of
      this revue is to perform an update on the various situations that can be
      observed, the principles of management of these liver diseases, in order to
      reduce the risk of complications and to ensure the best maternal and fetal
      prognosis. 

PMID- 25591871
TI  - Femoral Neck Stress Fractures and Imaging Features of Femoroacetabular
      Impingement.
AB  - BACKGROUND: Prior literature has suggested an association between the
      radiographic signs of femoroacetabular impingement (FAI) and femoral neck stress
      fractures (FNSF) or femoral neck stress reactions (FNSR). At the time of the
      writing of this article, no study has described the association of FAI and
      FNSF/FNSR along with the need for surgical intervention and outcomes. OBJECTIVE:
      To determine the prevalence of radiographic features of FAI in patients diagnosed
      with FNSF. DESIGN: Retrospective case series. SETTING: Tertiary care,
      institutional setting. PATIENTS: A medical records search program (Stanford
      Translational Research Integrated Database Environment, Stanford University,
      California) was used to retrospectively search for patients 18-40 years old with
      a history of FNSF or FNSR. The records were obtained from the period July 25,
      2003, to September 23, 2011. METHODS: For assessment of risk factors, plain
      radiographs and magnetic resonance imaging studies were reviewed for features of
      cam or pincer FAI. Medical records were reviewed to determine whether patients
      required operative intervention. MAIN OUTCOME MEASURES: Incidence of abnormal
      alpha (alpha) angle, abnormal anterior offset ratio, abnormal femoral head-neck
      junction, coxa profunda, positive crossover sign, and abnormal lateral center-to
      edge angle. RESULTS: Twenty-one female and 3 male participants (mean age 27
      years, range 19-39 years) were identified with magnetic resonance imaging
      evidence of femoral neck stress injury. Cam morphology was seen in 10 patients
      (42%). Pincer morphology could be assessed in 18 patients, with coxa profunda in
      14 (78%) and acetabular retroversion in 6 (14%). Features of combined pincer and
      cam impingement were observed in 4 patients (17%). Seven patients (29%) had
      operative intervention, with 3 (12%) requiring internal fixation of their femoral
      neck fractures, and all had radiographic evidence of fracture union after
      surgery. Four patients (17%) had persistent symptoms after healing of their FNSF
      with conservative treatment and eventually required surgery for FAI, 3 had no
      pain at final follow-up 1 year post-surgery, and one patient was lost to follow
      up. CONCLUSION: The results of the current study suggest that patients in the
      general population with femoral neck stress injuries have a higher incidence of
      bony abnormalities associated with pincer impingement, including coxa profunda
      and acetabular retroversion, although it is unclear whether pincer FAI is a true
      risk factor in the development of FNSF.

PMID- 25591872
TI  - Reduced expression of the MDA5 Gene IFIH1 prevents autoimmune diabetes.
AB  - Although it is widely accepted that type 1 diabetes (T1D) is the result of the
      autoimmune destruction of insulin-producing beta-cells in the pancreas, little is
      known about the events leading to islet autoimmunity. Epidemiological and genetic
      data have associated virus infections and antiviral type I interferon (IFN-I)
      response genes with T1D. Genetic variants in the T1D risk locus interferon
      induced with helicase C domain 1 (IFIH1) have been identified by genome-wide
      association studies to confer resistance to T1D and result in the reduction in
      expression of the intracellular RNA virus sensor known as melanoma
      differentiation-associated protein 5 (MDA5). Here, we translate the reduction in
      IFIH1 gene expression that results in protection from T1D. Our functional studies
      demonstrate that mice heterozygous at the Ifih1 gene express less than half the
      level of MDA5 protein, which leads to a unique antiviral IFN-I signature and
      adaptive response after virus infection that protects from T1D. IFIH1
      heterozygous mice have a regulatory rather than effector T-cell response at the
      site of autoimmunity, supporting IFIH1 expression as an essential regulator of
      the diabetogenic T-cell response and providing a potential mechanism for patients
      carrying IFIH1 protective polymorphisms.

PMID- 25591873
TI  - Diazoxide improves hormonal counterregulatory responses to acute hypoglycemia in
      long-standing type 1 diabetes.
AB  - Individuals with long-standing type 1 diabetes (T1D) are at increased risk of
      severe hypoglycemia secondary to impairments in normal glucose counterregulatory
      responses (CRRs). Strategies to prevent hypoglycemia are often ineffective,
      highlighting the need for novel therapies. ATP-sensitive potassium (KATP)
      channels within the hypothalamus are thought to be integral to hypoglycemia
      detection and initiation of CRRs; however, to date this has not been confirmed in
      human subjects. In this study, we examined whether the KATP channel-activator
      diazoxide was able to amplify the CRR to hypoglycemia in T1D subjects with long
      duration diabetes. A randomized, double-blind, placebo-controlled cross-over
      trial using a stepped hyperinsulinemic hypoglycemia clamp was performed in 12 T1D
      subjects with prior ingestion of diazoxide (7 mg/kg) or placebo. Diazoxide
      resulted in a 37% increase in plasma levels of epinephrine and a 44% increase in
      plasma norepinephrine during hypoglycemia compared with placebo. In addition, a
      subgroup analysis revealed that the response to oral diazoxide was blunted in
      participants with E23K polymorphism in the KATP channel. This study has therefore
      shown for the first time the potential utility of KATP channel activators to
      improve CRRs to hypoglycemia in individuals with T1D and, moreover, that it may
      be possible to stratify therapeutic approaches by genotype.

PMID- 25591874
TI  - Differences in the activity budgets of Yunnan snub-nosed monkeys (Rhinopithecus
      bieti) by age-sex class at Xiangguqing in Baimaxueshan Nature Reserve, China.
AB  - The activity budgets of primates reflect their survival strategy. Despite
      existing data on the activity budgets of Yunnan snub-nosed monkeys (Rhinopithecus
      bieti), little is known about how activity budgets vary between age-sex classes.
      This study provides the first detailed activity budgets subdivided by age-sex
      class, based on observations of the largest habituated group of R. bieti at
      Xiangguqing in Baimaxueshan Nature Reserve. This study was conducted from June
      2008 to May 2009. We found that adult females spent more time feeding (44.8%)
      than adult males (39.5%), juveniles (39.1%) and infants (14.2%). Females
      allocated significantly more time to feeding than to any other activity. Adult
      males allocated more time to miscellaneous activities (12.5%) than adult females
      (3.8%). Juveniles allocated less time to grooming than adults. Infants were being
      groomed 6.9% of the time, the highest proportion among all age-sex classes.
      Adults spent more time feeding, while immature individuals allocated more time to
      moving and other activities. There are several reasons why activity budgets can
      vary by age-sex class: (1) differential reproductive investment between males and
      females; (2) developmental differences among the age categories, and (3) social
      relationships between members of different age-sex classes, particularly
      dominance. These variations in activity budgets among the different age-sex
      classes may become a selective pressure in this species.

PMID- 25591875
TI  - Principles for supplying virus-tested material.
AB  - Production of virus-tested material of vegetatively propagated crops through
      national certification schemes has been implemented in many developed countries
      for more than 60 years and its importance for being the best virus control means
      is well acknowledged by growers worldwide. The two most important elements of
      certification schemes are the use of sensitive, reliable, and rapid detection
      techniques to check the health status of the material produced and effective and
      simple sanitation procedures for the elimination of viruses if present in
      candidate material before it enters the scheme. New technologies such as next
      generation sequencing platforms are expected to further enhance the efficiency of
      certification and production of virus-tested material, through the clarification
      of the unknown etiology of several graft-transmissible diseases. The successful
      production of virus-tested material is a demanding procedure relying on the close
      collaboration of researchers, official services, and the private sector.
      Moreover, considerable efforts have been made by regional plant protection
      organizations such as the European and Mediterranean Plant Protection
      Organization (EPPO), the North American Plant Protection Organization (NAPPO),
      and the European Union and the USA to harmonize procedures, methodologies, and
      techniques in order to assure the quality, safety, and movement of the
      vegetatively propagated material produced around the world. 

PMID- 25591876
TI  - Control of sweet potato virus diseases.
AB  - Sweet potato (Ipomoea batatas) is ranked seventh in global food crop production
      and is the third most important root crop after potato and cassava. Sweet
      potatoes are vegetative propagated from vines, root slips (sprouts), or tubers.
      Therefore, virus diseases can be a major constrain, reducing yields markedly,
      often more than 50%. The main viruses worldwide are Sweet potato feathery mottle
      virus (SPFMV) and Sweet potato chlorotic stunt virus (SPCSV). Effects on yields
      by SPFMV or SPCSV alone are minor, or but in complex infection by the two or
      other viruses yield losses of 50%. The orthodox way of controlling viruses in
      vegetative propagated crops is by supplying the growers with virus-tested
      planting material. High-yielding plants are tested for freedom of viruses by PCR,
      serology, and grafting to sweet potato virus indicator plants. After this,
      meristem tips are taken from those plants that reacted negative. The meristems
      were grown into plants which were kept under insect-proof conditions and away
      from other sweet potato material for distribution to farmers after another cycle
      of reproduction. 

PMID- 25591877
TI  - Control of pome and stone fruit virus diseases.
AB  - Many different systemic pathogens, including viruses, affect pome and stone
      fruits causing diseases with adverse effects in orchards worldwide. The
      significance of diseases caused by these pathogens on tree health and fruit shape
      and quality has resulted in the imposition of control measures both nationally
      and internationally. Control measures depend on the identification of diseases
      and their etiological agents. Diagnosis is the most important aspect of
      controlling fruit plant viruses. Early detection of viruses in fruit trees or in
      the propagative material is a prerequisite for their control and to guarantee a
      sustainable agriculture. Many quarantine programs are in place to reduce spread
      of viruses among countries during international exchange of germplasm. All these
      phytosanitary measures are overseen by governments based on agreements produced
      by international organizations. Also certification schemes applied to fruit trees
      allow the production of planting material of known variety and plant health
      status for local growers by controlling the propagation of pathogen-tested mother
      plants. They ensure to obtain propagative material not only free of "quarantine"
      organisms under the national legislation but also of important "nonquarantine"
      pathogens. The control of insect vectors plays an important role in the systemic
      diseases management, but it must be used together with other control measures as
      eradication of infected plants and use of certified propagation material. Apart
      from the control of the virus vector and the use of virus-free material, the
      development of virus-resistant cultivars appears to be the most effective
      approach to achieve control of plant viruses, especially for perennial crops that
      are more exposed to infection during their long life span. The use of resistant
      or tolerant cultivars and/or rootstocks could be potentially the most important
      aspect of virus disease management, especially in areas in which virus infections
      are endemic. The conventional breeding for virus-tolerant or resistant fruit tree
      cultivars using available germplasm is a long-term strategy, and the development
      and production of these cultivars may take decades, if successful. Genetic
      engineering allows the introduction of specific DNA sequences offering the
      opportunity to obtain existing fruit tree cultivars improved for the desired
      resistance trait. Unfortunately, genetic transformation of pome and stone fruits
      is still limited to few commercial genotypes. Research carried out and the new
      emerging biotechnological approaches to obtain fruit tree plants resistant or
      tolerant to viruses are discussed. 

PMID- 25591878
TI  - Cassava virus diseases: biology, epidemiology, and management.
AB  - Cassava (Manihot esculenta Crantz.) is the most important vegetatively propagated
      food staple in Africa and a prominent industrial crop in Latin America and Asia.
      Its vegetative propagation through stem cuttings has many advantages, but
      deleteriously it means that pathogens are passed from one generation to the next
      and can easily accumulate, threatening cassava production. Cassava-growing
      continents are characterized by specific suites of viruses that affect cassava
      and pose particular threats. Of major concern, causing large and increasing
      economic impact in Africa and Asia are the cassava mosaic geminiviruses that
      cause cassava mosaic disease in Africa and Asia and cassava brown streak viruses
      causing cassava brown streak disease in Africa. Latin America, the center of
      origin and domestication of the crop, hosts a diverse set of virus species, of
      which the most economically important give rise to cassava frog skin disease
      syndrome. Here, we review current knowledge on the biology, epidemiology, and
      control of the most economically important groups of viruses in relation to both
      farming and cultural practices. Components of virus control strategies examined
      include: diagnostics and surveillance, prevention and control of infection using
      phytosanitation, and control of disease through the breeding and promotion of
      varieties that inhibit virus replication and/or movement. We highlight areas that
      need further research attention and conclude by examining the likely future
      global outlook for virus disease management in cassava. 

PMID- 25591879
TI  - Control of virus diseases of citrus.
AB  - Citrus is thought to have originated in Southeast Asia and horticulturally
      desirable clonal selections have been clonally cultivated for hundreds of years.
      While some citrus species have nucellar embryony, most cultivation of citrus has
      been by clonal propagation to ensure that propagated plants have the same traits
      as the parent selection. Clonal propagation also avoids juvenility, and the
      propagated plants produce fruit sooner. Because of the clonal propagation of
      citrus, citrus has accumulated a large number of viruses; many of these viruses
      are asymptomatic until a susceptible rootstock and/or scion is encountered. The
      viruses reported to occur in citrus will be summarized in this review. Methods of
      therapy to clean selected clones from viruses will be reviewed; the use of
      quarantine, clean stock, and certification programs for control of citrus viruses
      and other strategies to control insect spread citrus viruses, such as mild strain
      cross-protection and the use of pest management areas will be discussed. 

PMID- 25591880
TI  - Control of viruses infecting grapevine.
AB  - Grapevine is a high value vegetatively propagated fruit crop that suffers from
      numerous viruses, including some that seriously affect the profitability of
      vineyards. Nowadays, 64 viruses belonging to different genera and families have
      been reported in grapevines and new virus species will likely be described in the
      future. Three viral diseases namely leafroll, rugose wood, and infectious
      degeneration are of major economic importance worldwide. The viruses associated
      with these diseases are transmitted by mealybugs, scale and soft scale insects,
      or dagger nematodes. Here, we review control measures of the major grapevine
      viral diseases. More specifically, emphasis is laid on (i) approaches for the
      production of clean stocks and propagative material through effective sanitation,
      robust diagnosis, as well as local and regional certification efforts, (ii) the
      management of vectors of viruses using cultural, biological, and chemical
      methods, and (iii) the production of resistant grapevines mainly through the
      application of genetic engineering. The benefits and limitations of the different
      control measures are discussed with regard to accomplishments and future research
      directions. 

PMID- 25591882
TI  - Control of virus diseases of berry crops.
AB  - Virus control in berry crops starts with the development of plants free of
      targeted pathogens, usually viruses, viroids, phytoplasmas, and systemic
      bacteria, through a combination of testing and therapy. These then become the top
      tier plants in certification programs and are the source from which all certified
      plants are produced, usually after multiple cycles of propagation. In
      certification schemes, efforts are made to produce plants free of the targeted
      pathogens to provide plants of high health status to berry growers. This is
      achieved using a systems approach to manage virus vectors. Once planted in fruit
      production fields, virus control shifts to disease control where efforts are
      focused on controlling viruses or virus complexes that result in disease. In
      fruiting fields, infection with a virus that does not cause disease is of little
      concern to growers. Virus control is based on the use of resistance and
      tolerance, vector management, and isolation. 

PMID- 25591881
TI  - Biology, etiology, and control of virus diseases of banana and plantain.
AB  - Banana and plantain (Musa spp.), produced in 10.3 million ha in the tropics, are
      among the world's top 10 food crops. They are vegetatively propagated using
      suckers or tissue culture plants and grown almost as perennial plantations. These
      are prone to the accumulation of pests and pathogens, especially viruses which
      contribute to yield reduction and are also barriers to the international exchange
      of germplasm. The most economically important viruses of banana and plantain are
      Banana bunchy top virus (BBTV), a complex of banana streak viruses (BSVs) and
      Banana bract mosaic virus (BBrMV). BBTV is known to cause the most serious
      economic losses in the "Old World," contributing to a yield reduction of up to
      100% and responsible for a dramatic reduction in cropping area. The BSVs exist as
      episomal and endogenous forms are known to be worldwide in distribution. In India
      and the Philippines, BBrMV is known to be economically important but recently the
      virus was discovered in Colombia and Costa Rica, thus signaling its spread into
      the "New World." Banana and plantain are also known to be susceptible to five
      other viruses of minor significance, such as Abaca mosaic virus, Abaca bunchy top
      virus, Banana mild mosaic virus, Banana virus X, and Cucumber mosaic virus.
      Studies over the past 100 years have contributed to important knowledge on
      disease biology, distribution, and spread. Research during the last 25 years have
      led to a better understanding of the virus-vector-host interactions, virus
      diversity, disease etiology, and epidemiology. In addition, new diagnostic tools
      were developed which were used for surveillance and the certification of planting
      material. Due to a lack of durable host resistance in the Musa spp.,
      phytosanitary measures and the use of virus-free planting material are the major
      methods of virus control. The state of knowledge on BBTV, BBrMV, and BSVs, and
      other minor viruses, disease spread, and control are summarized in this review. 

PMID- 25591883
TI  - This volume covers control of vegetative propagated crops and follows the
      previous one on control in seed-propagated ones. Preface.

PMID- 25591884
TI  - Margaret McCartney: Combination of exercise and social interaction is why I love
      parkrun.

PMID- 25591885
TI  - Thirty years of experience with intraductal papillary mucinous neoplasm of the
      pancreas: from discovery to international consensus.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is
      characterized by intraductal papillary proliferation of mucin-producing
      epithelial cells that exhibit various degrees of dysplasia. IPMN is classified as
      the main duct type (MD-IPMN) and the branch duct type (BD-IPMN) according to the
      location of involvement, and into four histological subtypes (gastric,
      intestinal, pancreatobiliary, and oncocytic) according to the histomorphological
      and immunohistochemical characteristics. Mucin core protein expression correlates
      with the biological behavior and prognosis of the tumor. DNA analysis has shown
      that IPMN is associated with a number of gene mutations, but the roles of many of
      these mutations require further investigation. Most patients with MD-IPMN undergo
      tumor resection. Patients with BD-IPMN who do not undergo resection may develop
      malignant change, and concomitant separate pancreatic cancer occurs in 2-10% of
      patients with IPMN. Patients with a strong family history may develop multiple BD
      IPMNs as well as concomitant pancreatic cancer. Malignant changes are relatively
      easy to detect, especially by endoscopic ultrasonography (EUS), but the optimal
      surveillance protocol is currently unclear. KEY MESSAGES: The 2012 guidelines for
      the management of IPMN recommend that patients with 'high-risk stigmata'
      (obstructive jaundice, enhanced solid component, and main pancreatic duct size
      >=10 mm) should undergo resection. Patients with 'worrisome features' (cyst size
      >=3 cm, thickened enhanced cyst walls, non-enhanced mural nodules, main
      pancreatic duct size 5-9 mm, abrupt change in main pancreatic duct caliber with
      distal pancreatic atrophy, lymphadenopathy, and clinical acute pancreatitis)
      should be evaluated by EUS. EUS is a more sensitive test than computed tomography
      or magnetic resonance imaging for the early detection of malignancy. CONCLUSIONS:
      Most patients with MD-IPMN should undergo tumor resection. Patients with BD-IPMN
      who do not undergo resection should undergo careful surveillance including EUS
      for the early detection of malignant change and separate pancreatic cancer.

PMID- 25591886
TI  - Emerging fractal patterns in a real 3D cerebral aneurysm.
AB  - The behaviour of biological fluid flows is often investigated in medical practice
      to draw conclusions on the physiological or pathological conditions of the
      considered organs. One area where such investigations are proven to be useful is
      the flow-related formation and growth of different pathologic malformations of
      the cerebro-vascular system. In this work, a detailed study is presented on the
      effect of a cerebral aneurysm on blood transport inside a human brain artery
      segment. This malformation causes strong flow instabilities that drives the flow
      system towards chaotic behaviour. The emerging fractal structure and some of its
      measurable properties have been explored using a method that makes the
      measurement of these properties feasible even in complicated large three
      dimensional data sets. We find that, from the investigated chaos parameters, the
      information dimension turns out to be the most reliable parameter to characterise
      chaotic advection in the vicinity of the aneurysm sac. We propose that properties
      of chaotic mixing close to aneurysms might be relevant for the condition of this
      pathologic malformation. 

PMID- 25591887
TI  - Size change, shape change, and the growth space of a community.
AB  - Measures of biodiversity change such as the Living Planet Index describe
      proportional change in the abundance of a typical species, which can be thought
      of as change in the size of a community. Here, I discuss the orthogonal concept
      of change in relative abundances, which I refer to as shape change. To be
      logically consistent, a measure of the rate of shape change should be scaling
      invariant (have the same value for all data with the same vector of proportional
      change over a given time interval), but existing measures do not have this
      property. I derive a new, scaling invariant measure. I show that this new measure
      and existing measures of biodiversity change such as the Living Planet Index
      describe different aspects of dynamics. I show that neither body size nor
      environmental variability need affect the rate of shape change. I extend the
      measure to deal with colonizations and extinctions, using the surreal number
      system. I give examples using data on hoverflies in a garden in Leicester, UK,
      and the higher plant community of Surtsey. I hypothesize that phylogenetically
      restricted assemblages will show a higher proportion of size change than diverse
      communities. 

PMID- 25591888
TI  - Short-term consolidation of articular cartilage in the long-term context of
      osteoarthritis.
AB  - Over ten percent of the population are afflicted by osteoarthritis, a chronic
      disease of diarthrodial joints such as the knees and hips, costing hundreds of
      billions of dollars every year. In this condition, the thin layers of articular
      cartilage on the bones degrade and weaken over years, causing pain, stiffness and
      eventual immobility. The biggest controllable risk factor is long-term mechanical
      overloading of the cartilage, but the disparity in time scales makes this process
      a challenge to model: loading events can take place every second, whereas
      degradation occurs over many months. Therefore, a suitable model must be
      sufficiently simple to permit evaluation over long periods of variable loading,
      yet must deliver results sufficiently accurate to be of clinical use, conditions
      unmet by existing models. To address this gap, we construct a two-component
      poroelastic model endowed with a new flow restricting boundary condition, which
      better represents the joint space environment compared to the typical free-flow
      condition. Under both static and cyclic loading, we explore the rate of gradual
      consolidation of the medium. In the static case, we analytically characterise the
      duration of consolidation, which governs the duration of effective fluid-assisted
      lubrication. In the oscillatory case, we identify a region of persistent strain
      oscillations in otherwise consolidated tissue, and derive estimates of its depth
      and magnitude. Finally, we link the two cases through the concept of an
      equivalent static stress, and discuss how our results help explain the inexorable
      cartilage degeneration of osteoarthritis. 

PMID- 25591889
TI  - Precision assessment of some supervised and unsupervised algorithms for genotype
      discrimination in the genus Pisum using SSR molecular data.
AB  - For the first time, prediction accuracies of some supervised and unsupervised
      algorithms were evaluated in an SSR-based DNA fingerprinting study of a pea
      collection containing 20 cultivars and 57 wild samples. In general, according to
      the 10 attribute weighting models, the SSR alleles of PEAPHTAP-2 and PSBLOX13.2-1
      were the two most important attributes to generate discrimination among eight
      different species and subspecies of genus Pisum. In addition, K-Medoids
      unsupervised clustering run on Chi squared dataset exhibited the best prediction
      accuracy (83.12%), while the lowest accuracy (25.97%) gained as K-Means model ran
      on FCdb database. Irrespective of some fluctuations, the overall accuracies of
      tree induction models were significantly high for many algorithms, and the
      attributes PSBLOX13.2-3 and PEAPHTAP could successfully detach Pisum fulvum
      accessions and cultivars from the others when two selected decision trees were
      taken into account. Meanwhile, the other used supervised algorithms exhibited
      overall reliable accuracies, even though in some rare cases, they gave us low
      amounts of accuracies. Our results, altogether, demonstrate promising
      applications of both supervised and unsupervised algorithms to provide suitable
      data mining tools regarding accurate fingerprinting of different species and
      subspecies of genus Pisum, as a fundamental priority task in breeding programs of
      the crop. 

PMID- 25591890
TI  - Superconductivity at 52 K in hydrogen-substituted LaFeAsO(1-x)Hx under high
      pressure.
AB  - The 1111-type iron-based superconductor LnFeAsO(1-x)Fx (Ln stands for lanthanide)
      is the first material with a Tc above 50 K, other than cuprate superconductors.
      Electron doping into LaFeAsO by H, rather than F, revealed a double-dome-shaped
      Tc-x diagram, with a first dome (SC1, 0.05<x<0.20) and a second dome (SC2,
      0.2<x<0.5). Here, we report the Tc for the whole hydrogen-doping range in
      LaFeAsO(1-x)Hx under pressures of up to 19 GPa. Tc rises to 52 K at 6 GPa for the
      Tc-valley composition between the two Tc domes. This is the first instance of the
      Tc exceeding 50 K in La-1111-type iron-based superconductors. On the other hand,
      the Tc of SmFeAsO1-x)Hx decreased continually, keeping its single-dome structure
      up to 15 GPa. The present findings strongly suggest that t(he main reason for
      realization of the Tc >50 K observed in RE-1111 compounds (RE: Pr, Sm, and Gd) at
      ambient pressure is the merging of SC1 and SC2.

PMID- 25591891
TI  - Identifying and mobilizing assets for health - the optimists' charter.

PMID- 25591892
TI  - Clinical significance of a spiral phenomenon in the plot of CO2 output versus O2
      uptake during exercise in cardiac patients.
AB  - A spiral phenomenon is sometimes noted in the plots of CO2 output (VCO2) against
      O2 uptake (VO2) measured during cardiopulmonary exercise testing (CPX) in
      patients with heart failure with oscillatory breathing. However, few data are
      available that elucidate the clinical significance of this phenomenon. Our group
      studied the prevalence of this phenomenon and its relation to cardiac and
      cardiopulmonary function. Of 2,263 cardiac patients who underwent CPX, 126
      patients with a clear pattern of oscillatory breathing were identified.
      Cardiopulmonary indexes were compared between patients who showed the spiral
      phenomenon (n = 49) and those who did not (n = 77). The amplitudes of VO2 and
      VCO2 oscillations were greater and the phase difference between VO2 and VCO2
      oscillations was longer in the patients with the spiral phenomenon than in those
      without it. Patients with the spiral phenomenon also had a lower left ventricular
      ejection fraction (43.4 +/- 21.4% vs 57.1 +/- 16.8%, p <0.001) and a higher level
      of brain natriuretic peptide (637.2 +/- 698.3 vs 228.3 +/- 351.4 pg/ml, p =
      0.002). The peak VO2 was lower (14.5 +/- 5.6 vs 18.1 +/- 6.3, p = 0.002), the
      slope of the increase in ventilation versus VCO2 was higher (39.8 +/- 9.5 vs 33.6
      +/- 6.8, p <0.001), and end-tidal PCO2 both at rest and at peak exercise was
      lower in the patients with the spiral phenomenon than in those without it. In
      conclusion, the spiral phenomenon in the VCO2-versus-VO2 plot arising from the
      phase difference between VCO2 and VO2 oscillations reflects more advanced
      cardiopulmonary dysfunction in cardiac patients with oscillatory breathing.

PMID- 25591893
TI  - Effects of atorvastatin and rosuvastatin on renal function in patients with type
      2 diabetes mellitus.
AB  - We performed this population-based study to investigate the effects of
      atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes.
      From the Taiwan National Health Insurance Pay-for-Performance program for
      diabetes mellitus database, 2006 to 2009, type 2 diabetic patients aged 40 to 100
      years with the first prescription of atorvastatin or rosuvastatin were
      identified. All the data were linked to the National Health Insurance claims
      database, 2000 to 2010, to construct longitudinal health care data. The
      Modification of Diet in Renal Disease equation was used to calculate the
      estimated glomerular filtration rate (eGFR), and the eGFRs between baseline and
      the end of follow-up (maximum 2 years) were compared. Totally, 3,601 new users of
      atorvastatin and 1,968 new users of rosuvastatin were included. The median follow
      up was 238 days in atorvastatin users and 210 days in rosuvastatin users. The
      eGFR at baseline was 72.3 +/- 25.9 ml/min/1.73 m(2) in atorvastatin users and
      73.7 +/- 27.3 ml/min/1.73 m(2) in rosuvastatin users. In both statin groups, we
      found no significant change in eGFR (+0.1 ml/min/1.73 m(2), 95% confidence
      interval -0.4 to 0.7, p = 0.62 in atorvastatin users; -0.1 ml/min/1.73 m(2), 95%
      confidence interval -0.8 to 0.6, p = 0.77 in rosuvastatin users). In conclusion,
      neither treatment with atorvastatin nor rosuvastatin was associated with a
      significant change of renal function in type 2 diabetic patients.

PMID- 25591894
TI  - Diagnostic yield of patch ambulatory electrocardiogram monitoring in children
      (from a national registry).
AB  - The diagnostic yield of continuous electrocardiographic (ECG) monitoring in
      children for periods longer than a Holter monitor is unclear. The aim of this
      study was to characterize diagnostic yield, arrhythmia type, and time to first
      arrhythmia using a clinical repository of national ambulatory ECG data in
      children. A cross-sectional study was performed in 3,209 consecutive children
      receiving a 14-day adhesive patch monitor (Zio Patch) for clinical indications
      from January 2011 to December 2013. Of the 3,209 children (56% female, mean age
      12.5 +/- 4.4 years, range 1 month to 17 years), 390 had arrhythmias detected,
      making the diagnostic yield 12.2%. Of these, 137 patients (4.3%) had arrhythmias
      deemed clinically significant to warrant urgent physician notification. The most
      frequent indications for monitoring were palpitations (n = 1,138 [35.5%]),
      syncope (n = 450 [14.0%]), unspecified tachycardia (n = 291 [9.1%]),
      supraventricular tachycardia (n = 264 [8.2%]), and chest pain (n = 261 [8.1%]).
      Arrhythmias were detected in 10.0% of patients with palpitations, 6.7% of
      patients with syncope, 14.8% of patients with tachycardia, 22.7% of patients with
      supraventricular tachycardia, and 6.5% of patients with chest pain. The mean
      times to first detected and first symptom-triggered arrhythmias were 2.7 +/- 3.0
      and 3.3 +/- 3.3 days, respectively. Forty-four percent of first detected
      arrhythmias and 50.4% of the first symptom-triggered arrhythmias occurred beyond
      48 hours of monitoring. In conclusion, the diagnostic yield of continuous ECG
      patch monitoring in children was substantial beyond 48 hours and should be
      considered in children who are candidates for longer term ECG monitoring.

PMID- 25591895
TI  - Effect of aortic regurgitation following transcatheter aortic valve implantation
      on outcomes.
AB  - The prognosis of aortic regurgitation (AR) after transcatheter aortic valve
      implantation (TAVI) and the changes in AR grade over time remain unclear. This
      study evaluated the midterm survival associated with AR after TAVI and examined
      the evolution of AR over time and its effect on cardiac performance. Successful
      TAVI was performed in 314 patients (age 81 +/- 7 years, 36% men). Serial
      transthoracic echocardiography and clinical assessment were available in 175
      patients who survived >12 months. AR was assessed in terms of overall,
      paravalvular, and intravalvular severity. Significant post-TAVI AR (grade >=2)
      was observed in 82 patients (26%), and these patients showed a trend toward
      reduced survival at 1- (93% vs 91%) and 2-year (89% vs 74%, log-rank p = 0.063)
      follow-up. Of the 175 patients who survived >12 months, grade >=2 overall,
      paravalvular, and intravalvular AR were noted in 47 (27%), 32 (18%), and 8
      patients (5%), respectively. Significant overall and paravalvular AR appeared to
      improve over time, particularly during the first 6 months (p <0.05), whereas
      intravalvular AR remained unchanged. Although improvements in the
      echocardiographic parameters were similar among patients with and without
      significant AR, patients who remained with grade >=2 AR at 6 months had
      significantly worse survival than their counterparts at 2 years (80% vs 94%, log
      rank p = 0.032). In conclusion, significant overall and paravalvular AR after
      TAVI appeared to improve over time. Although improvements in the
      echocardiographic parameters were similar, patients with grade >=2 AR, both
      immediately after TAVI and at 6 months, were associated with worse survival.

PMID- 25591896
TI  - Usefulness of retinal microvascular endothelial dysfunction as a predictor of
      coronary artery disease.
AB  - Endothelial dysfunction is a key feature of atherosclerosis. Retinal
      microvascular endothelial function can be assessed using noninvasive dynamic
      vessel imaging techniques. Whether it is impaired in subjects with coronary
      artery disease (CAD) is unknown. The aim of this study was to examine the
      relation of retinal microvascular endothelial function with CAD. Vascular studies
      were performed in 197 prospectively recruited subjects divided into 2 groups:
      those without CAD but >=2 cardiovascular risk factors (non-CAD controls; n = 119)
      and those with stable CAD (n = 78). Retinal microvascular endothelial dysfunction
      was assessed by measuring retinal arteriolar and venular dilatation to flicker
      light, a nitric oxide-dependent phenomenon, expressed as percentage increase over
      baseline diameter. Fingertip pulse-volume amplitude was measured to calculate
      reactive hyperaemia index and brachial artery flow-mediated dilatation assessed
      as measures of peripheral microvascular and conduit vessel endothelial function,
      respectively. Mean retinal arteriolar dilatation was attenuated in patients with
      CAD compared with non-CAD controls (1.51 +/- 1.51% vs 2.37 +/- 1.95%, p = 0.001).
      Retinal arteriolar dilatation was independently associated with CAD after
      adjustment for age, gender, cardiovascular risk factors, and medication use (odds
      ratio 1.60, 95% confidence interval 1.14 to 2.25, p = 0.007). Reactive hyperaemia
      index and flow-mediated dilatation were not different. In conclusion, the
      capacity of retinal arterioles to dilate in response to flicker light is an
      independent predictor of the presence of CAD and suggests that retinal
      microvascular endothelial dysfunction is a marker for underlying CAD. 

PMID- 25591897
TI  - Relation of contrast induced nephropathy to new onset atrial fibrillation in
      acute coronary syndrome.
AB  - Chronic renal failure has been described as a risk factor for the development of
      atrial fibrillation (AF). The aim of this study was to examine the association
      between contrast-induced nephropathy (CIN) and new-onset AF in patients with
      acute coronary syndromes. A total of 1,520 consecutive patients (mean age 67.1 +/
      12.7 years) with acute coronary syndromes (34.4% with ST-segment elevation
      myocardial infarctions) who underwent coronary angiography were studied. CIN was
      defined as an increase in serum creatinine of 0.5 mg/dl within 72 hours of
      contrast exposure. The independent effect of AF history (chronic or paroxysmal AF
      before catheterization) on the development of CIN, as well as the independent
      effect of CIN on the development of new-onset AF (after catheterization, during
      the in-hospital phase), were tested by using different logistic regression
      models. One hundred thirty-nine patients (9.1%) had histories of AF before
      catheterization (60 with paroxysmal and 79 with chronic AF), and 56 (4.1%)
      developed new-onset AF after catheterization. Eighty-seven patients (5.7%) had
      CIN. AF history was a predictor of CIN in univariate analysis (odds ratio 2.19,
      95% confidence interval 1.22 to 3.95, p = 0.007) but not in multivariate
      analysis, after adjusting for confounding variables (odds ratio 1.69, 95%
      confidence interval 0.89 to 3.22, p = 0.111). In contrast, those with CIN had an
      increased prevalence of new-onset AF (15.3% vs 3.4%, p <0.001). After adjusting
      for those variables associated with new-onset AF in the univariate analysis, CIN
      continued to show a significant association with new-onset AF, with a twofold
      increased risk (odds ratio 2.45, 95% confidence interval 1.07 to 5.64, p =
      0.035). In conclusion, the development of CIN is an independent predictor of new
      onset AF in the context of acute coronary syndromes.

PMID- 25591898
TI  - Prevalence of intracardiac thrombi under phenprocoumon, direct oral
      anticoagulants (dabigatran and rivaroxaban), and bridging therapy in patients
      with atrial fibrillation and flutter.
AB  - Direct oral anticoagulants (DOACs) are effective for stroke prevention in
      nonvalvular atrial fibrillation (AF). Cardioversion (CV) is frequently performed
      in patients with AF or flutter. To further explore the safety profile of DOACs in
      the context of CV, we sought to assess the prevalence of intracardiac thrombi
      under DOAC therapy in comparison with treatment with vitamin K antagonists. A
      total of 672 transesophageal echocardiograms performed in 643 patients with a
      history of nonvalvular AF were analyzed. The median CHA2DS2-VASc score was 4.
      Cases were stratified according to anticoagulation with dabigatran (n = 79),
      rivaroxaban (n = 122), phenprocoumon (n = 180), or bridging therapy (n = 287). In
      a subgroup analysis, only patients receiving phenprocoumon with an international
      normalized ratio >=2 on the day of the investigation or on DOAC therapy for >=3
      weeks were considered. The prevalence of intracardiac thrombi under phenprocoumon
      was significantly higher than under DOACs (phenprocoumon, 17.8%; all DOACs, 3.9%;
      dabigatran, 3.8%; rivaroxaban, 4.1%) and showed no significant difference to
      bridging therapy (12.5%). In patients with sufficient short-term anticoagulation,
      similar differences between DOAC and phenprocoumon groups were observed
      (phenprocoumon, 18.4%; all DOACs, 3.8%; dabigatran, 0%; rivaroxaban, 6.6%). The
      influence of anticoagulation medication on thrombus rates was confirmed after
      adjusting for baseline intergroup differences regarding left atrial size and
      CHA2DS2-VASc score. In conclusion, the prevalence of intracardiac thrombi was
      lower under DOAC therapy than under phenprocoumon in this high-risk patient
      cohort. Safety of CV during DOAC treatment requires further prospective
      evaluation.

PMID- 25591899
TI  - Long-term benefit of myectomy and anterior mitral leaflet extension in
      obstructive hypertrophic cardiomyopathy.
AB  - Severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HC)
      may benefit from surgical myectomy. In patients with enlarged mitral leaflets and
      mitral regurgitation, myectomy can be combined with anterior mitral leaflet
      extension (AMLE) to stiffen the midsegment of the leaflet. The aim of this study
      was to evaluate the long-term results of myectomy combined with AMLE in patients
      with obstructive HC. This prospective, observational, single-center cohort study
      included 98 patients (49 +/- 14 years, 37% female) who underwent myectomy
      combined with AMLE from 1991 to 2012. End points included all-cause mortality and
      change in clinical and echocardiographic characteristics. Mortality was compared
      with age- and gender-matched patients with nonobstructive HC and subjects from
      the general population. Long-term follow-up was 8.3 +/- 6.1 years. There was no
      operative mortality, and New York Heart Association class was reduced from 2.8 +/
      0.5 to 1.3 +/- 0.5 (p <0.001), left ventricular outflow tract gradient from 93
      +/- 25 to 9 +/- 8 mm Hg (p <0.001), mitral valve regurgitation from grade 2.0 +/-
      0.9 to 0.5 +/- 0.8 (p <0.001), and systolic anterior motion of the mitral valve
      from grade 2.4 +/- 0.9 to 0.1 +/- 0.3 (p <0.001). The 1-, 5-, 10-, and 15-year
      cumulative survival rates were 98%, 92%, 86%, and 83%, respectively, and did not
      differ from the general population (99%, 97%, 92%, and 85%, respectively, p =
      0.3) or patients with nonobstructive HC (98%, 97%, 88%, and 83%, respectively, p
      = 0.8). In conclusion, in selected patients with obstructive HC, myectomy
      combined with AMLE is a low-risk surgical procedure. It results in long-term
      symptom relief and survival similar to the general population.

PMID- 25591900
TI  - [Atypical genesis of anterior ischemic optic neuropathy].
AB  - BACKGROUND: This article presents a case of arteritic anterior ischemic optic
      neuropathy as a manifestation of granulomatosis with polyangiitis (GPA). CASE
      REPORT: A 52-year-old woman suffered acute unilateral vision loss. Besides a
      unilateral papillary edema, serological investigations revealed elevated
      inflammation parameters with a positive (cytoplasmic) anti-neutrophil cytoplasmic
      autoantibodies (c-ANCA) titer. In addition to the occurrence of pulmonary nodules
      and cavitary lesions this is indicative for the diagnosis of GPA. RESULTS:
      Treatment with cyclophosphamide and prednisolone led to a rapid regression of
      inflammation parameters but no visual improvement occurred.

PMID- 25591901
TI  - [Vernal keratoconjunctivitis].
AB  - Vernal keratoconjunctivitis (VKC) is a bilateral, usually seasonally recurrent
      inflammation of the conjunctiva. Clinically characteristic findings are tarsal
      giant conjunctival papillae (> 1 mm) and/or limbal gelatinous changes (Trantas
      dots). The underlying etiology and pathophysiology of VKC remains unclear;
      however, clinical findings and immunohistochemical studies suggest a complex,
      both IgE-dependent and IgE-independent immune-mediated etiology. Several
      predisposing conditions include endocrine, genetic, neurogenic, environmental and
      socioeconomic risk factors. Mast cell stabilizers, antihistamines and topical
      corticosteroids are often used during acute flare-ups in VKC; however this
      approach is unsatisfactory for controlling severe cases and avoiding recurrences.
      Immunomodulatory agents, such as cyclosporin A and tacrolimus are promising
      alternative agents for long-term management. In most children the clinical course
      of VKC is self-limiting and may disappear following puberty; however, some VKC
      patients will face sight-threatening complications which are mainly due to
      corneal involvement and iatrogenic damage caused by prolonged corticosteroid
      treatment. 

PMID- 25591902
TI  - Multiplex PCR for the detection and quantification of zoonotic taxa of Giardia,
      Cryptosporidium and Toxoplasma in wastewater and mussels.
AB  - Giardia duodenalis, Cryptosporidium parvum and Toxoplasma gondii are important
      parasitic protists linked to water- and food-borne diseases. The accurate
      detection of these pathogens is central to the diagnosis, tracking, monitoring
      and surveillance of these protists in humans, animals and the environment. In
      this study, we established a multiplex real-time PCR (qPCR), coupled to high
      resolution melting (HRM) analysis, for the specific detection and quantification
      of each G. duodenalis (assemblage A), C. parvum and T. gondii (Type I). Once
      optimised, this assay was applied to the testing of samples (n = 232) of treated
      wastewater and mussels (Mytilus galloprovincialis). Of 119 water samples, 28.6%
      were test-positive for G. duodenalis, C. parvum and/or both pathogens; of 113
      mussel samples, 66.6% were test-positive for G. duodenalis, C. parvum and/or both
      pathogens, and 13.2% were test-positive for only T. gondii. The specificity of
      all amplicons produced was verified by direct sequencing. The oo/cysts numbers
      (per 5 MUl of DNA sample) ranged from 10 to 64. The present multiplex assay
      achieved an efficiency of 100% and a R(2) value of >0.99. Current evidence
      indicates that this assay provides a promising tool for the simultaneous
      detection and quantitation of three key protist taxa.

PMID- 25591904
TI  - Alexithymia, responsibility attitudes and suicide ideation among outpatients with
      obsessive-compulsive disorder: an exploratory study.
AB  - AIMS: Obsessive-compulsive disorder (OCD) is psychiatric disorder with a
      significant suicide risk, and the presence of alexithymia may increase this risk.
      As several studies attribute an important role, in OCD, to responsibility, the
      aims of this study were to evaluate possible clinical differences between
      patients positive or not for alexithymia concerning disorder severity,
      responsibility attitudes and suicide ideation and investigate which variables
      were associated with increased suicide ideation. METHODS: 104 adult outpatients
      with OCD were recruited. Alexithymia was measured with Toronto Alexithymia Scale
      (TAS-20), attitude about responsibility was tested with Responsibility Attitude
      Scale (RAS), suicide ideation was assessed with Scale of Suicide Ideation (SSI)
      and depressive symptoms were evaluated with Montgomery Asberg Depression Rating
      Scale (MADRS). Score of item #11 on the Y-BOCS was considered as a measure of
      insight. RESULTS: Patients positive for alexithymia showed higher responsibility
      attitudes and more severe suicide ideation. In a blockwise regression model, the
      presence of lower insight, higher RAS scores and difficulty in identifying
      feelings dimension of TAS-20 were associated with higher SSI scores. CONCLUSIONS:
      OCD patients with alexithymia may show higher disorder severity, lower insight
      and inflated responsibility, all related to suicide ideation, independently from
      depressive symptoms. Implications were discussed and study limitations considered
      and reported.

PMID- 25591903
TI  - The association between BMP4 gene polymorphism and its serum level with the
      incidence of LVH in hypertensive patients.
AB  - BACKGROUND: Bone morphogenic proteins 4 (BMP4) is associated with cardiac
      remodeling under different conditions. However, the role of BMP4 and its gene
      polymorphism in the incidence of left ventricular hypertrophy (LVH) in
      hypertensive patients remains unknown. METHODS: A total of 1265 patients
      diagnosed with essential hypertension (EH) were recruited. Patients were assigned
      to LVH+ (n = 420) and LVH- (n = 845) groups. serum BMP4 level was measured and
      two single nucleotide polymorphism (SNPs) polymorphisms, 6007C > T and -5826G > A
      of BMP4 gene were genotyped. We also inhibited the BMP4 by small interfering RNA
      (siRNA). The effect of BMP4 on the hypertrophic response in Human Cardiomyocytes
      AC16 cells was studied. RESULTS: We found that the 6007C > T polymorphism of the
      BMP4 gene and the serum BMP4 level were significantly associated with the risk to
      develop LVH. With TT as reference, multivariate logistic regression analysis
      showed the 6007CC genotype carriers had a higher susceptibility to LVH incidence
      (adjusted OR = 2.65, 95% CI: 1.63-4.31, adjusted P < 0.001). Our in vitro study
      shows that the BMP4 inhibition in cardiomyocyte by si-RNA technique significantly
      decreased the Ang II induced cardiomyocyte size and protein content per cell,
      indicating the importance of BMP4 in the cardiomyocyte hypertrophy. CONCLUSION:
      Collectively, our data suggest that both the 6007C > T of the BMP4 gene and the
      serum BMP4 level may be used as potential marker for LVH incidence among the EH
      patients.

PMID- 25591905
TI  - Sensory modulation and daily-life participation in people with schizophrenia.
AB  - Schizophrenia is considered to be an extreme mental health disturbance that
      affects a person's well-being and participation in everyday activities.
      Participation in meaningful everyday occupations is an important component of
      recovery from mental illness, the ultimate goal of mental health services. The
      participation restrictions of people with schizophrenia have been widely
      investigated through different factors, such as illness symptoms and course,
      cognition, and demographic data; however, the resulting explanations were
      incomplete. The purpose of the study was to explore the contribution of sensory
      modulation (SM), in addition to cognition and schizophrenia symptoms, to
      participation in daily life activities of people with schizophrenia. Forty nine
      in-patients with schizophrenia (study group) and 32 adults without mental illness
      (control group) comprised the study. They were assessed for their participation
      patterns, sensory modulation processes, cognitive functioning and symptoms
      severity. Results indicate significant differences between the study groups in
      most measurements addressed: participation (diversity and satisfaction), sensory
      modulation scores (intensity of the response and frequency of response), and
      cognitive measurements. The most contributive parameters for the prediction of
      participation dimensions among people with schizophrenia were negative symptoms
      severity and general cognitive status. In conclusion, people with schizophrenia
      experience SM disorder with an under responsive tendency. However the complex
      condition of schizophrenia dominates its influence on participation dimensions. 

PMID- 25591906
TI  - Correlates of dependence and treatment for substance use among people with
      comorbid severe mental and substance use disorders: findings from the
      "Psychiatric and Addictive Dual Disorder in Italy (PADDI)" Study.
AB  - OBJECTIVE: People with severe mental illness (SMI) have often comorbid alcohol
      and other substance disorders but substantial barriers to addiction care remain.
      The study is aimed at describing correlates associated with dependence and with
      treatment for substance use among people with SMI and comorbid substance
      disorders cared in community mental health teams (CMHTs). METHODS: This study
      capitalized on data from a national survey on comorbid severe mental and
      substance use disorders, among 2235 subjects in 42 CMHTs nationwide. RESULTS: 26%
      of people with SMI and comorbid misuse suffered from dependence on alcohol and
      21% on any other substance. Use of opioids, liver diseases, involvement with
      criminal justice system, but also area of residence, all were associated with
      dependence in people with SMI. As regards treatment for substance use, only 50%
      of comorbid people with SMI were treated by specialist services in the past 12
      months. This was associated with opioids and cocaine use, as well as with liver
      diseases, and involvement with criminal justice. People with schizophrenia and
      those living in Central and Southern Italy, had the lowest chances to be treated
      for their comorbid substance use disorder. CONCLUSIONS: There are extensive unmet
      treatment needs among comorbid individuals with SMI. Better integration of
      substance abuse and mental health care systems, and more effective reciprocal
      referral procedures, are needed.

PMID- 25591907
TI  - The variable region of iodothyronine deiodinases directs their catalytic
      properties and subcellular localization.
AB  - The stereospecific removal of iodine from thyroid hormones is an essential first
      step for T3 action and is catalyzed by three different deiodinases: D2 and D3
      remove iodine only from the outer or inner ring, respectively, whereas D1
      catalyzes both pathways. We used in silico predictions from vertebrate deiodinase
      sequences to identify two domains: the N-terminal variable region (VR) containing
      the transmembrane, hinge and linker domains, and the conserved or globular region
      (CR). Given the high sequence and structural identity of the CR among paralogs as
      well as of the VR among orthologs but not paralogs, we hypothesized that both the
      catalytic properties and the subcellular localization rely on the VR. We used
      shark D2 and D3 as templates to build the chimeric enzymes D2VR/D3CR and
      D3VR/D2CR. Biochemical characterization revealed that D3VR/D2CR has inner-ring
      deiodination activity and T3 as preferred substrate, whereas D2VR/D3CR showed no
      deiodinating activity. Also, D2VR/D3CR and D3VR/D2CR reside in the endoplasmic
      reticulum and plasmatic membrane, respectively, as do their D2 and D3 wild-type
      counterparts. We conclude that the VR determines the subcellular localization and
      is critical in defining the catalytic properties and activity of thyroid hormone
      deiodinases. 

PMID- 25591908
TI  - STC1 interference on calcitonin family of receptors signaling during
      osteoblastogenesis via adenylate cyclase inhibition.
AB  - Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in
      bone formation/remodeling. Here we investigate the effects of STC1 on functional
      heterodimer complex CALCRL/RAMP1, expression and activity during
      osteoblastogenesis. STC1 did not modify CALCRL and ramp1 gene expression during
      osteoblastogenesis when compared to controls. However, plasma membrane spatial
      distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to
      either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP,
      but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in
      CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin
      stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected
      HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor
      (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1
      signals through inhibitory G-protein modulates CGRP receptor spatial localization
      during osteoblastogenesis and may function as a regulatory factor interacting
      with calcitonin peptide members during bone formation. 

PMID- 25591909
TI  - Detection and quantification of residues and metabolites of medicinal products in
      environmental compartments, food commodities and workplaces. A review.
AB  - The toxicological assessment of medicinal products (MPs) and their residues and
      metabolites in the environment have become a challenging task worldwide. The
      contamination of environmental compartments, biota, workplace, foodstuff and
      feedstuff by residues and metabolites of these substances poses a risk to human
      health which is still far from being fully understood. On the other hand,
      existing analytical methods not always possess sufficient detection power to
      quantify residues of MPs at very low concentrations. This review sets forth some
      of the most significant contributions made in this field over the past decade
      with a special focus on novel fit-for-purpose analytical approaches for the
      detection, identification and quantification of these pollutants and the
      assessment of their noxious potential for human beings and the environment. 

PMID- 25591910
TI  - Improving the Cooperation Rate of Older Adults and Their Caregivers in Research
      Surveys.
AB  - BACKGROUND: Recruiting older adults, their family members and their home care
      workers as participants in research studies is particularly complicated. This
      might be due to medical or cognitive problems of the older adult as well as the
      high workload and shortage of time experienced by caregivers. The present study
      compared the contribution of two different versions of an advanced letter
      followed by two different versions of a recruitment phone call to the cooperation
      rate of older adults, family caregivers and home care workers in a face-to-face
      survey. METHODS: A quasi-experimental design was used to compare the contribution
      of the different types of appeal. A total of 2,014 caregiving units (composed of
      an older adult, a family member and a home care worker) were randomly sampled
      from a list of Israeli long-term care insurance beneficiaries. 74.32% of the
      sampled caregiving units were eligible to participate in the study. The first
      group of participants received formal and succinctly phrased written and oral
      appeals - an advanced letter followed by a recruitment phone call. The second
      group of participants received the original formal and succinctly phrased
      advanced letter, but a revised recruitment phone call that included a more
      personal approach, the provision of broader information about the study and the
      avoidance of words with a possible negative connotation. The third group of
      participants received both a revised advanced letter and a revised recruitment
      phone call. RESULTS: Using the succinctly phrased written and oral appeals, we
      had a cooperation rate of about 50% for the entire caregiving unit. Using a
      revised advanced letter and a revised recruitment phone call yielded an increase
      of 20-25% in the cooperation rate for the entire caregiving unit. Using the
      revised recruitment phone call and the original advanced letter yielded an
      increase in the cooperation rate only among migrant home care workers.
      CONCLUSION: This study showed that by changing the format of appeal we can
      increase the cooperation rate of older adults and their caregivers in a research
      survey. This study also pointed out the importance of the advanced letter.

PMID- 25591911
TI  - Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by
      polyinosinic-polycytidylic acid in U373MG human astrocytoma cells.
AB  - Although iron is essential in physiological processes, accumulation of iron in
      central nervous system is associated with various neurological diseases including
      Alzheimer's disease and Parkinson's disease. Innate immune reactions are involved
      in the pathogenesis of those diseases, but roles of iron in innate immunity are
      not known well. In the present study, pretreatment of U373MG human astrocytoma
      cells with an iron chelator desferrioxamine (DFX) inhibited the expression of
      CXCL10 induced by a Toll-like receptor 3 (TLR3) agonist polyinosinic
      polycytidylic acid (poly IC). Induction of interferon-beta (IFN-beta) was not
      affected, but phosphorylation of signal transducer and transcription 1 (STAT1)
      was decreased by DFX. We have previously reported that various IFN-stimulated
      genes (ISGs) are involved in CXCL10 induction by poly IC. Pretreatment with DFX
      also decreased the expression of these ISGs. Pretreatment of cells with FeSO4
      counteracted inhibitory effects of DFX on ISG56, retinoic acid-inducible gene-I
      (RIG-I), CXCL10 and phosphorylation of STAT1. These results suggest that iron may
      positively regulate STAT1 phosphorylation and following signaling to express
      ISG56, RIG-I and CXCL10 in U373MG cells treated with poly IC. Iron may contribute
      to innate immune and inflammatory reactions elicited by the TLR3 signaling in
      astrocytes, and may play an important role in neuroinflammatory diseases. 

PMID- 25591913
TI  - DIDS reduces ischemia/reperfusion-induced myocardial injury in rats.
AB  - BACKGROUND/AIMS: Anion channels such as chloride channel are known to participate
      in the regulation of a wide variety of cellular processes including development,
      differentiation, proliferation, apoptosis and regeneration. This study was
      designed to examine the effect of the non-selective anion channel blocker 4,4'
      Diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) on cardiac function and
      apoptosis using a rat model of ischemia/reperfusion (I/R). METHODS: Fifty male SD
      rats were randomly divided into the following groups including sham, I/R and
      I/R+DIDS (7, 14 or 28 mg/kg). In DIDS group, rats received DIDS treatment (4
      ml/kg/hr) at the beginning of reperfusion for 2 hrs using a programmed micro
      pump. Cardiac function was evaluated including left ventricular systolic pressure
      (LVSP), left ventricular end diastolic pressure (LVEDP) as well as positive and
      negative maximal derivatives of left ventricular pressure (+/- dP/dt(max)).
      Myocardial infarct size was detected using the double staining with 2, 3, 5
      triphenyl-2H-tetra-zolium chloride (TTC) and Evan's blue dye. DNA ladder, TUNEL
      assay, Bax and Bcl-2 protein levels were evaluated. Levels of ROS and Akt
      phosphorylation were detected. RESULTS: I/R injury compromised cardiac function
      as manifested by reduced LVSP and +/- dP/dt(max) as well as pronounced apoptosis.
      I/R-induced cardiac anomalies were markedly ameliorated by DIDS. DIDS retarded
      I/R-induced myocardial infarct and apoptosis. In addition, DIDS ameliorated I/R
      induced ROS production and Akt dephosphorylation in the heart. CONCLUSION: Taken
      together, our data revealed that DIDS may protect cardiomyocytes against I/R
      injury as evidenced by improved cardiac function, Bcl-2, Akt phosphorylation, and
      reduced myocardial apoptosis, Bax expression, ROS production and myocardial
      infarct size.

PMID- 25591912
TI  - Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8+ T
      cell immune response and antitumor effects in a preclinical cervical cancer
      model.
AB  - BACKGROUND: Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic
      acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been
      recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved
      for the treatment of cutaneous T cell lymphoma and multiple myeloma/mantle cell
      lymphoma, respectively. Furthermore, the combination of the bortezomib and SAHA
      has been tested in a variety of preclinical models and in clinical trials and may
      be ideal for the treatment of cancer. However, it remains unclear how this
      treatment strategy affects the host immune response against tumors. RESULTS:
      Here, we used a well-defined E6/E7-expressing tumor model to examine how the
      immune system can be motivated to act against tumor cells expressing tumor
      antigens. We demonstrate that the combination of bortezomib and SAHA elicits
      potent antitumor effects in TC-1 tumor-bearing mice. Additionally, we are the
      first to show that treatment with bortezomib and SAHA leads to tumor-specific
      immunity by rendering tumor cells more susceptible to killing by antigen-specific
      CD8+ T cells than treatment with either drug alone. CONCLUSIONS: The current
      study serves an important foundation for the future clinical application of both
      drugs for the treatment of cervical cancer.

PMID- 25591914
TI  - A simple method for comparing enzymatic capecitabine activation in various mono-
      and combination chemotherapies.
AB  - Before being able to develop a pharmacodynamic effect, a number of drugs have to
      be activated by enzymes, which are known to be potentially influenced by manifold
      factors, leading to a possible alteration of their activity behaviour. Based on
      capecitabine, we report a simple and rapid method for the estimation and
      comparison of the so-called 'apparent enzyme activity' (R), not only intra-
      (different dose levels) but also inter-schedule, to contribute to therapeutic
      success. Dividing the area under the curve (AUC) of the product by the AUC of the
      precursor generates a factor which indicates the apparent activity of the enzyme
      involved in the biotransformation of a compound. Our own data as well as data
      from the literature was used to calculate those R levels revealing that the
      formation of 5'-DFUR - the immediate precursor of 5-fluorouracil - was not
      affected by concomitant medication within the dosing range investigated.
      Calculated hypothetical means of R for carboxylesterase (1.49 +/- 0.66) and for
      cytidine deaminase (1.17 +/- 0.65) were obtained. Additionally, it is important
      to note that the method described in this report is of general use and not
      limited to chemotherapeutic agents, as soon as enzymes are involved in drug
      activation.

PMID- 25591915
TI  - "The sky is the limit": adhering to antiretroviral therapy and HIV self
      management from the perspectives of adolescents living with HIV and their adult
      caregivers.
AB  - INTRODUCTION: Worldwide, HIV-related mortality among adolescents living with HIV
      (ALHIV) increased by 50% from 2005 to 2012 and is attributed in part to a lack of
      support for adolescent retention to care and adherence to antiretroviral therapy
      (ART). This vulnerability reinforces the need to better understand incomplete ART
      adherence among ALHIV, particularly in sub-Saharan Africa, where the majority of
      the world's 2.1 million ALHIV reside. METHODS: From December 2011 to February
      2012, we conducted in-depth interviews with 32 ALHIV (aged 15 to 18) and 23 of
      their adult caregivers in the Copperbelt Province of Zambia. Interviews were
      transcribed and translated. An iterative qualitative process was used to code and
      analyze the data and main themes were summarized regarding the barriers to and
      facilitators of ART adherence. RESULTS: More than a quarter of ALHIV reported
      missing a day or more of ART (ranging from one day to six months). Barriers to
      ART adherence included fear of disclosure and anticipated stigma. Few youth were
      willing to take their drugs outside of the home, which led to missed doses of
      ART. Similarly, families tended to manage HIV within the home only. As a result,
      although caregivers and families were often the greatest source of emotional and
      instrumental support, they coped with HIV in isolation of other potential support
      from their communities, schools or churches. Factors that supported ART adherence
      included attending clinic-sponsored youth groups, wanting to maintain one's
      health and using phone and clock alarms. Involvement of adult caregivers in HIV
      management varied greatly and was often based on the age and health status of the
      youth. Some caregivers struggled with letting the adolescents assume
      responsibility for their medication, and ALHIV had few self-management skills and
      tools to help them regularly take ART. CONCLUSIONS: These data highlight the
      importance of families and home environments in supporting adherence to ART among
      ALHIV. Skill-building and family-based interventions to prepare ALHIV and their
      adult caregivers for HIV self-management and HIV status disclosure by youth are
      of paramount importance. Future research and programmes also need to address the
      fears adolescents and families have regarding HIV-related stigma that shape young
      peoples' adherence behaviours.

PMID- 25591916
TI  - Avoiding misannotation of in-source fragmentation products as cellular
      metabolites in liquid chromatography-mass spectrometry-based metabolomics.
AB  - Liquid chromatography-mass spectrometry (LC-MS) technology allows for rapid
      quantitation of cellular metabolites, with metabolites identified by mass
      spectrometry and chromatographic retention time. Recently, with the development
      of rapid scanning high-resolution high accuracy mass spectrometers and the desire
      for high throughput screening, minimal or no chromatographic separation has
      become increasingly popular. When analyzing complex cellular extracts, however,
      the lack of chromatographic separation could potentially result in misannotation
      of structurally related metabolites. Here, we show that, even using electrospray
      ionization, a soft ionization method, in-source fragmentation generates unwanted
      byproducts of identical mass to common metabolites. For example, nucleotide
      triphosphates generate nucleotide-diphosphates, and hexose-phosphates generate
      triose-phosphates. We evaluated yeast intracellular metabolite extracts and found
      more than 20 cases of in-source fragments that mimic common metabolites.
      Accordingly, chromatographic separation is required for accurate quantitation of
      many common cellular metabolites. 

PMID- 25591918
TI  - In vitro evaluation and in vivo demonstration of a biomimetic, hemocompatible,
      microfluidic artificial lung.
AB  - Despite the promising potential of microfluidic artificial lungs, current designs
      suffer from short functional lifetimes due to surface chemistry and blood flow
      patterns that act to reduce hemocompatibility. Here, we present the first
      microfluidic artificial lung featuring a hemocompatible surface coating and a
      biomimetic blood path. The polyethylene-glycol (PEG) coated microfluidic lung
      exhibited a significantly improved in vitro lifetime compared to uncoated
      controls as well as consistent and significantly improved gas exchange over the
      entire testing period. Enabled by our hemocompatible PEG coating, we additionally
      describe the first extended (3 h) in vivo demonstration of a microfluidic
      artificial lung. 

PMID- 25591917
TI  - Predicting protein functions using incomplete hierarchical labels.
AB  - BACKGROUND: Protein function prediction is to assign biological or biochemical
      functions to proteins, and it is a challenging computational problem
      characterized by several factors: (1) the number of function labels (annotations)
      is large; (2) a protein may be associated with multiple labels; (3) the function
      labels are structured in a hierarchy; and (4) the labels are incomplete. Current
      predictive models often assume that the labels of the labeled proteins are
      complete, i.e. no label is missing. But in real scenarios, we may be aware of
      only some hierarchical labels of a protein, and we may not know whether
      additional ones are actually present. The scenario of incomplete hierarchical
      labels, a challenging and practical problem, is seldom studied in protein
      function prediction. RESULTS: In this paper, we propose an algorithm to Predict
      protein functions using Incomplete hierarchical LabeLs (PILL in short). PILL
      takes into account the hierarchical and the flat taxonomy similarity between
      function labels, and defines a Combined Similarity (ComSim) to measure the
      correlation between labels. PILL estimates the missing labels for a protein based
      on ComSim and the known labels of the protein, and uses a regularization to
      exploit the interactions between proteins for function prediction. PILL is shown
      to outperform other related techniques in replenishing the missing labels and in
      predicting the functions of completely unlabeled proteins on publicly available
      PPI datasets annotated with MIPS Functional Catalogue and Gene Ontology labels.
      CONCLUSION: The empirical study shows that it is important to consider the
      incomplete annotation for protein function prediction. The proposed method (PILL)
      can serve as a valuable tool for protein function prediction using incomplete
      labels. The Matlab code of PILL is available upon request.

PMID- 25591919
TI  - Linkage analysis and map construction in genetic populations of clonal F1 and
      double cross.
AB  - In this study, we considered four categories of molecular markers based on the
      number of distinguishable alleles at the marker locus and the number of
      distinguishable genotypes in clonal F1 progenies. For two marker loci, there are
      nine scenarios that allow the estimation of female, male, and/or combined
      recombination frequencies. In a double cross population derived from four inbred
      lines, five categories of markers are classified and another five scenarios are
      present for recombination frequency estimation. Theoretical frequencies of
      identifiable genotypes were given for each scenario, from which the maximum
      likelihood estimates of one or more of the three recombination frequencies could
      be estimated. If there was no analytic solution, then Newton-Raphson method was
      used to acquire a numerical solution. We then proposed to use an algorithm in
      Traveling Salesman Problem to determine the marker order. Finally, we proposed a
      procedure to build the two haploids of the female parent and the two haploids of
      the male parent in clonal F1. Once the four haploids were built, clonal F1
      hybrids could be exactly regarded as a double cross population. Efficiency of the
      proposed methods was demonstrated in simulated clonal F1 populations and one
      actual maize double cross. Extensive comparisons with software JoinMap4.1,
      OneMap, and R/qtl show that the methodology proposed in this article can build
      more accurate linkage maps in less time. 

PMID- 25591920
TI  - Evolutionary consequences of DNA methylation on the GC content in vertebrate
      genomes.
AB  - The genomes of many vertebrates show a characteristic variation in GC content. To
      explain its origin and evolution, mainly three mechanisms have been proposed:
      selection for GC content, mutation bias, and GC-biased gene conversion. At
      present, the mechanism of GC-biased gene conversion, i.e., short-scale,
      unidirectional exchanges between homologous chromosomes in the neighborhood of
      recombination-initiating double-strand breaks in favor for GC nucleotides, is the
      most widely accepted hypothesis. We here suggest that DNA methylation also plays
      an important role in the evolution of GC content in vertebrate genomes. To test
      this hypothesis, we investigated one mammalian (human) and one avian (chicken)
      genome. We used bisulfite sequencing to generate a whole-genome methylation map
      of chicken sperm and made use of a publicly available whole-genome methylation
      map of human sperm. Inclusion of these methylation maps into a model of GC
      content evolution provided significant support for the impact of DNA methylation
      on the local equilibrium GC content. Moreover, two different estimates of
      equilibrium GC content, one that neglects and one that incorporates the impact of
      DNA methylation and the concomitant CpG hypermutability, give estimates that
      differ by approximately 15% in both genomes, arguing for a strong impact of DNA
      methylation on the evolution of GC content. Thus, our results put forward that
      previous estimates of equilibrium GC content, which neglect the hypermutability
      of CpG dinucleotides, need to be reevaluated. 

PMID- 25591921
TI  - Modeling transversely isotropic, viscoelastic, incompressible tissue-like
      materials with application in ultrasound shear wave elastography.
AB  - In this paper, we propose a method to model the shear wave propagation in
      transversely isotropic, viscoelastic and incompressible media. The targeted
      application is ultrasound-based shear wave elastography for viscoelasticity
      measurements in anisotropic tissues such as the kidney and skeletal muscles. The
      proposed model predicts that if the viscoelastic parameters both across and along
      fiber directions can be characterized as a Voigt material, then the spatial phase
      velocity at any angle is also governed by a Voigt material model. Further, with
      the aid of Taylor expansions, it is shown that the spatial group velocity at any
      angle is close to a Voigt type for weakly attenuative materials within a certain
      bandwidth. The model is implemented in a finite element code by a time domain
      explicit integration scheme and shear wave simulations are conducted. The results
      of the simulations are analyzed to extract the shear wave elasticity and
      viscosity for both the spatial phase and group velocities. The estimated values
      match well with theoretical predictions. The proposed theory is further verified
      by an ex vivo tissue experiment measured in a porcine skeletal muscle by an
      ultrasound shear wave elastography method. The applicability of the Taylor
      expansion to analyze the spatial velocities is also discussed. We demonstrate
      that the approximations from the Taylor expansions are subject to errors when the
      viscosities across or along the fiber directions are large or the maximum
      frequency considered is beyond the bandwidth defined by radii of convergence of
      the Taylor expansions. 

PMID- 25591922
TI  - Research by residents: obstacles and opportunities.
AB  - As the psychiatric field continues to evolve in a world with nascent mobile
      technology (Hilty et al., 2014), novel neuroscience and genetic research, and new
      payment and care models (Fried et al., 2014) it is likely that the psychiatry
      residents learn today will not match what they will be practicing tomorrow.
      Residents have the opportunity to help shape that future through conducting
      research today. While the prospect of research can initially seem daunting to the
      busy resident, here we examine, from psychiatry residents' perspective, the
      common pitfalls and rewards of research during residency. 

PMID- 25591923
TI  - Dealing with ethical challenges: a focus group study with professionals in mental
      health care.
AB  - BACKGROUND: Little is known about how health care professionals deal with ethical
      challenges in mental health care, especially when not making use of a formal
      ethics support service. Understanding this is important in order to be able to
      support the professionals, to improve the quality of care, and to know in which
      way future ethics support services might be helpful. METHODS: Within a project on
      ethics, coercion and psychiatry, we executed a focus group interview study at
      seven departments with 65 health care professionals and managers. We performed a
      systematic and open qualitative analysis focusing on the question: 'How do health
      care professionals deal with ethical challenges?' We deliberately did not present
      a fixed definition or theory of ethical challenge. RESULTS: We categorized
      relevant topics into three subthemes: 1) Identification and presence of ethical
      challenges; 2) What do the participants actually do when dealing with an ethical
      challenge?; and 3) The significance of facing ethical challenges. Results varied
      from dealing with ethical challenges every day and appreciating it as a positive
      part of working in mental health care, to experiencing ethical challenges as
      paralyzing burdens that cause a lot of stress and hinder constructive team
      cooperation. Some participants reported that they do not have the time and that
      they lack a specific methodology. Quite often, informal and retrospective ad-hoc
      meetings in small teams were organized. Participants struggled with what makes a
      challenge an ethical challenge and whether it differs from a professional
      challenge. When dealing with ethical challenges, a number of participants
      experienced difficulties handling disagreement in a constructive way.
      Furthermore, some participants plead for more attention for underlying intentions
      and justifications of treatment decisions. CONCLUSIONS: The interviewed health
      care professionals dealt with ethical challenges in many different ways, often in
      an informal, implicit and reactive manner. This study revealed nine different
      categories of what health care professionals implicitly or explicitly conceive as
      'ethical challenges'. Future research should focus on how ethics support
      services, such as ethics reflection groups or moral case deliberation, can be of
      help with respect to dealing with ethical challenges and value disagreements in a
      constructive way.

PMID- 25591924
TI  - Structural, optical and vibrational properties of self-assembled Pbn+1(Ti1-x
      Fex)nO(3n+1)-delta Ruddlesden-Popper superstructures.
AB  - Bulk crystals and thin films of PbTi(1-x)FexO3(-delta) (PTFO) are multiferroic,
      exhibiting ferroelectricity and ferromagnetism at room temperature. Here we
      report that the Ruddlesden-Popper phase Pbn+1(Ti(1-x)Fex)nO3(n+1)-delta forms
      spontaneously during pulsed laser deposition of PTFO on LaAlO3 substrates. High
      resolution transmission electron microscopy, x-ray diffraction and x-ray
      photoemission spectroscopy were utilised to perform a structural and
      compositional analysis, demonstrating that n ? 8 and x ? 0.5. The complex
      dielectric function of the films was determined from far-infrared to ultraviolet
      energies using a combination of terahertz time-domain spectroscopy, Fourier
      transform spectroscopy, and spectroscopic ellipsometry. The simultaneous Raman
      and infrared activity of phonon modes and the observation of second harmonic
      generation establishes a non-centrosymmetric point group for
      Pbn+1(Ti0.5Fe0.5)nO3(n+1)-delta, a prerequisite for (but not proof of)
      ferroelectricity. No evidence of macroscopic ferromagnetism was found in SQUID
      magnetometry. The ultrafast optical response exhibited coherent magnon
      oscillations compatible with local magnetic order, and additionally was used to
      study photocarrier cooling on picosecond timescales. An optical gap smaller than
      that of BiFeO3 and long photocarrier lifetimes may make this system interesting
      as a ferroelectric photovoltaic.

PMID- 25591925
TI  - Clinical profile and outcomes of women admitted to a psychiatric mother-baby
      unit.
AB  - This study examines the clinical profile of women admitted to a psychiatric
      mother-baby unit as well as change in their clinical, parenting, attachment and
      quality of life outcomes. Data was collected from 191 mothers through self-report
      measures at admission and discharge. Change was analysed in terms of Edinburgh
      Postnatal Depression Scale (EPDS) score, parenting confidence, maternal
      attachment to the infant and overall functioning. Psychosocial factors impacting
      on symptom severity and recovery were examined. Most women (64.8 %) were admitted
      in the first 3 months after birth with an ICD-10 unipolar depressive episode
      (52.3 %) or anxiety disorder (25.7 %), and 47.6 % had comorbid diagnoses.
      Improvement from admission to discharge was seen with large effect sizes (>=one
      standard deviation, i.e. MU) in terms of clinical symptoms (EPDS, MU = 1.7),
      parenting confidence (Karitane Parenting Confidence Scale (KPCS), MU = 1.1) and
      attachment to their infant (Maternal Postpartum Attachment Scale (MPAS), MU =
      0.9) as well as overall level of functioning (SF-14, MU = 1.9). The majority
      (73.3 %) recovered symptomatically, and this was associated with increasing
      maternal age (odds ratio (OR) = 1.129, p = 0.002) and lower levels of
      psychosocial risk at admission (OR = 0.963, p = 0.008). Improvement in parenting
      confidence was associated with increasing maternal age (OR = 1.17, p = 0.003). No
      predictive factors were found for improvement in maternal attachment after
      controlling for admission scores. In the short term, joint admission of mothers
      with their infants is highly beneficial in terms of clinical, functional and
      parenting outcomes, but follow up studies are needed to assess the longer term
      benefits for mother-infant dyads. The use of an observational tool to enhance our
      assessment of maternal-infant interaction and some measure of maternal emotional
      dysregulation-both important mediators of development of secure infant attachment
      would also enhance our ability to tailor therapeutic interventions. 

PMID- 25591926
TI  - Vitamin A-fortified cooking oil reduces vitamin A deficiency in infants, young
      children and women: results from a programme evaluation in Indonesia.
AB  - OBJECTIVE: To assess oil consumption, vitamin A intake and retinol status before
      and a year after the fortification of unbranded palm oil with retinyl palmitate.
      DESIGN: Pre-post evaluation between two surveys. SETTING: Twenty-four villages in
      West Java. SUBJECTS: Poor households were randomly sampled. Serum retinol
      (adjusted for subclinical infection) was analysed in cross-sectional samples of
      lactating mothers (baseline n 324/endline n 349), their infants aged 6-11 months
      (n 318/n 335) and children aged 12-59 months (n 469/477), and cohorts of children
      aged 5-9 years (n 186) and women aged 15-29 years (n 171), alongside food and oil
      consumption from dietary recall. RESULTS: Fortified oil improved vitamin A
      intakes, contributing on average 26 %, 40 %, 38 %, 29 % and 35 % of the daily
      Recommended Nutrient Intake for children aged 12-23 months, 24-59 months, 5-9
      years, lactating and non-lactating women, respectively. Serum retinol was 2-19 %
      higher at endline than baseline (P<0.001 in infants aged 6-11 months, children
      aged 5-9 years, lactating and non-lactating women; non-significant in children
      aged 12-23 months; P=0.057 in children aged 24-59 months). Retinol in breast milk
      averaged 20.5 MUg/dl at baseline and 32.5 MUg/dl at endline (P<0.01). Deficiency
      prevalence (serum retinol <20 MUg/dl) was 6.5-18 % across groups at baseline, and
      0.6-6 % at endline (P<=0.011). In multivariate regressions adjusting for socio
      economic differences, vitamin A intake from fortified oil predicted improved
      retinol status for children aged 6-59 months (P=0.003) and 5-9 years (P=0.03).
      CONCLUSIONS: Although this evaluation without a comparison group cannot prove
      causality, retinyl contents in oil, Recommended Nutrient Intake contributions and
      relationships between vitamin intake and serum retinol provide strong
      plausibility of oil fortification impacting vitamin A status in Indonesian women
      and children.

PMID- 25591927
TI  - Characterization and target identification of a DNA aptamer that labels
      pluripotent stem cells.

PMID- 25591930
TI  - Rare pathologies in the posterior third ventricular region in children: case
      series and review.
AB  - Tumors of the pineal region in children often belong to 2 categories, namely germ
      cell tumors and pineal parenchymal tumors. Very rare pathologies have previously
      been reported in this region. Most of these tumors may be similar radiologically,
      while their management differs. The present series reports 2 children with pineal
      region tumors, each one being a rare pathological entity by itself, namely an
      embryonal tumor with abundant neuropil and true rosettes (ETANTR) and a rosette
      forming glioneuronal tumor (RGNT). Very few such cases in each pathology have
      been reported in the literature for the pediatric age group up to now. Our series
      consists of 2 children, both presenting with a raised intracranial pressure of
      short duration. Imaging revealed lesions in the pineal region with similar
      radiological features. Both ETANTR and RGNT demonstrated mild enhancement. The 2
      patients underwent surgical decompression either by Poppen's approach (n = 1) or
      a supracerebellar infratentorial approach (n = 1). The patient with ETANTR was
      advised radiotherapy, while the child with RGNT was advised a regular follow-up.
      This series presents some rare pathologies which can occur in the posterior third
      ventricular region with similar radiological features. Management differs based
      on the histology of the case.

PMID- 25591929
TI  - Base-resolution maps of 5-formylcytosine and 5-carboxylcytosine reveal genome
      wide DNA demethylation dynamics.

PMID- 25591928
TI  - GATA family members as inducers for cellular reprogramming to pluripotency.
AB  - Members of the GATA protein family play important roles in lineage specification
      and transdifferentiation. Previous reports show that some members of the GATA
      protein family can also induce pluripotency in somatic cells by substituting for
      Oct4, a key pluripotency-associated factor. However, the mechanism linking
      lineage-specifying cues and the activation of pluripotency remains elusive. Here,
      we report that all GATA family members can substitute for Oct4 to induce
      pluripotency. We found that all members of the GATA family could inhibit the
      overrepresented ectodermal-lineage genes, which is consistent with previous
      reports indicating that a balance of different lineage-specifying forces is
      important for the restoration of pluripotency. A conserved zinc-finger DNA
      binding domain in the C-terminus is critical for the GATA family to induce
      pluripotency. Using RNA-seq and ChIP-seq, we determined that the pluripotency
      related gene Sall4 is a direct target of GATA family members during reprogramming
      and serves as a bridge linking the lineage-specifying GATA family to the
      pluripotency circuit. Thus, the GATA family is the first protein family of which
      all members can function as inducers of the reprogramming process and can
      substitute for Oct4. Our results suggest that the role of GATA family in
      reprogramming has been underestimated and that the GATA family may serve as an
      important mediator of cell fate conversion. 

PMID- 25591931
TI  - Evolution of acidic Ca2+ stores and their resident Ca2+-permeable channels.
AB  - Acidic Ca(2+) stores refer to a collection of H(+)- and Ca(2+)-rich organelles
      involved in Ca(2+) signalling across taxonomic kingdoms. They include lysosomes,
      lysosome-related organelles, secretory vesicles, vacuoles and acidocalcisomes.
      Acidic Ca(2+) stores express several types of Ca(2+)-permeable channels belonging
      to the TRP, TPC, P2X and IP3/ryanodine receptor families. The channels have
      distinct phylogenomic profiles, and each acidic Ca(2+) store possesses a distinct
      Ca(2+) channel portfolio. The functions of acidic Ca(2+) stores appear to be
      conserved in processes such as signalling, membrane traffic and "auto-secretion".
      Thus, despite substantial variation in form, acidic Ca(2+) stores may function
      similarly across the natural world. 

PMID- 25591932
TI  - The evolution of bacterial mechanosensitive channels.
AB  - Mechanosensitive channels are ubiquitous and highly studied. However, the
      evolution of the bacterial channels remains enigmatic. It can be argued that
      mechanosensitivity might be a feature of all membrane proteins with some becoming
      progressively less sensitive to membrane tension over the course of evolution.
      Bacteria and archaea exhibit two main classes of channels, MscS and MscL. Present
      day channels suggest that the evolution of MscL may be highly constrained,
      whereas MscS has undergone elaboration via gene fusion (and potentially gene
      fission) events to generate a diversity of channel structures. Some of these
      channel variants are constrained to a small number of genera or species. Some are
      only found in higher organisms. Only exceptionally have these diverse channels
      been investigated in any detail. In this review we consider both the processes
      that might have led to the evolved complexity but also some of the methods
      exploiting the explosion of genome sequences to understand (and/or track) their
      distribution. The role of MscS-related channels in calcium-mediated cell biology
      events is considered. 

PMID- 25591933
TI  - Dimer domain swapping versus monomer folding in apo-myoglobin studied by
      molecular simulations.
AB  - Recent experiments showed that myoglobin can form a domain-swapped dimer under
      certain conditions. Here, using a coarse-grained symmetrized Go model, we
      performed a series of folding simulations of two apo-myoglobin molecules
      restrained at a high density, addressing competition of formation of a domain
      swapped dimer with folding to two monomer structures. In addition to the domain
      swapped dimer found in X-ray crystallography, we also found some other forms of
      domain swapping. With the protein density, the probability of domain-swapping
      increased. Folding pathway analysis clarified that separation between monomer
      folding and domain-swapping arose at a relatively early stage, where inter-chain
      contacts between helices AB of one chain and helices GH of another chain tend to
      result in the domain swapped dimer. This resembles the mechanism of domain
      swapping suggested previously for cytochrome c. 

PMID- 25591934
TI  - Role of osteopontin in the regulation of human bladder cancer proliferation and
      migration in T24 cells.
AB  - Osteopontin (OPN), a secreted acid glycoprotein with a variety of functions,
      promotes tumor proliferation, differentiation, invasion and metastasis. The aim
      of the current study was to investigate whether OPN may serve as a potential
      therapeutic target for human bladder cancer. RNA interference (RNAi) was
      performed to downregulate the expression of the OPN gene in T24 human bladder
      cancer cells. The mRNA and protein expression levels of OPN following RNAi were
      determined using reverse transcription-quantitative polymerase chain reaction and
      western blot analysis, respectively. In addition, the cell cycle progression,
      apoptosis and proliferation were investigated using by flow cytometric analysis
      and MTT assay. The cell invasion ability was measured using a Matrigel transwell
      assay. The mRNA and protein expression levels of OPN were found to be
      significantly downregulated following RNAi. The proliferation and invasion of T24
      cells were significantly inhibited in vitro. In conclusion, RNAi-targeting OPN
      may inhibit the proliferation, invasion and tumorigenicity of human bladder
      cancer cells. Therefore, OPN may serve as a potential therapeutic target for
      human bladder cancer.

PMID- 25591935
TI  - A Phase I study of high-dose-rate intraluminal brachytherapy as palliative
      treatment in extrahepatic biliary tract cancer.
AB  - PURPOSE: To determine the recommended dose of endoscopically assisted high-dose
      rate intraluminal brachytherapy (HDR-192Ir-ILBT) as a palliative treatment of
      extrahepatic biliary tract cancer. METHODS AND MATERIALS: Patients with non
      metastatic extrahepatic biliary cancer with age <80 years, unsuitable for
      surgical resection or radiochemotherapy for comorbidities or Eastern Cooperative
      Oncology Group (ECOG) >=2 or patients with age >=80 years were included. They
      were undergone to implantation of metal stents by endoscopic retrograde
      cholangiopancreatography followed by HDR-192Ir-ILBT. The initial dose of HDR-192
      Ir-ILBT was 15 Gy. Three levels of dose were planned. At each dose level almost
      three patients were treated, and if no Grade 3-4 toxicity (considering as dose
      limiting toxicity) was recorded, dose escalation was applied with 5 Gy increments
      until the maximum tolerated dose was established. A high dose Iridium-192 after
      loading system was used (Nucletron Microselectron HDR). RESULTS: From May 2007 to
      January 2010, 18 patients underwent HDR-192Ir-ILBT, with one catheter in 12
      patients and two catheters in six patients. Three levels of dose were planned: 15
      Gy in three patients, 20 Gy in nine patients, and 25 Gy in six patients with
      daily dose of 500 cGy per fraction. One patient at Dose Level II experienced
      acute toxicity (cholangitis) related to brachytherapy procedure, so the cohort
      was expanded. No patient of Level III had a dose-limiting toxicity and we stopped
      at this dose level waiting to assess the late toxicity that has not yet appeared
      at the time of the analysis. Six months and 1 year overall survival was 77% and
      59%, respectively, with a median of 12 months. CONCLUSIONS: The recommended dose
      was defined as 25 Gy in five fractions. It will be used in a Phase II study to
      better evaluate tumor and symptom control in patients with extrahepatic biliary
      tract cancer.

PMID- 25591936
TI  - Reliability of sentinel node procedure for lymph node staging in prostate cancer
      patients at high risk for lymph node involvement.
AB  - AIM: To investigate the reliability of a sentinel node (SN) procedure for nodal
      staging in prostate cancer (PCa) patients at high risk for lymph node (LN)
      involvement. MATERIAL AND METHODS: Seventy-four patients with localized prostate
      adenocarcinoma, who were clinically node-negative and had a risk of LN
      involvement of >= 10% (Partin tables), were prospectively enrolled. Upon
      intraprostatic 99mTc-nanocolloid injection, they underwent planar scintigraphy
      and SPECT imaging. Surgical removal of the SN, located by means of a gamma probe,
      was completed with a superextended LN dissection (seLND) as a reference and
      followed by radical prostatectomy. RESULTS: In total, 470 SN (median 6, IQR 3-9)
      were scintigraphically detected of which 371 (median 4, IQR 2-6) were located by
      gamma probe and selectively removed during surgery (79%). Histopathology
      confirmed LN metastases in 37 patients (50%) having 106 affected LN in total
      (median number per patient 2, IQR 1-4). Twenty-eight patients were node positive
      (N+) based on the analysis of the resected SN. However, the seLND that was
      performed as a reference revealed nine additional N+ patients resulting in a
      sensitivity of 76% (28/37). In total, 15 of 37 patients (41%) had metastases in
      SN only and could have been spared seLND to remove all affected nodes.
      CONCLUSION: We found a relatively low sensitivity when addressing the SN
      procedure for nodal staging in PCa patients at high risk for LN involvement.
      Importantly, only less than half of the N+ patients could have been spared a
      seLND to remove all affected lymphoid tissue.

PMID- 25591937
TI  - Anterior-oriented proton beams for prostate cancer: A multi-institutional
      experience.
AB  - BACKGROUND: Proton beam therapy (PBT) for prostate cancer generally involves the
      use of two lateral beams that transverse the hips. In patients with hip
      replacements or a previously irradiated hip, this arrangement is contraindicated.
      The use of non-lateral beams is possible, but not well described. Here we report
      a multi-institutional experience for patients treated with at least one non
      lateral proton beam for prostate cancer. MATERIAL AND METHODS: Between 2010 and
      2014, 20 patients with organ-confined prostate cancer and a history of hip
      prosthesis underwent proton therapy utilizing at least one anterior oblique beam
      (defined as between 10 degrees  and 85 degrees  from vertical) at one of three
      proton centers. RESULTS: The median follow-up was 6.4 months. No patients have
      developed PSA failure or distant metastases. The median planning target volume
      (PTV) D95 was 79.2 Gy (RBE) (range 69.7-79.9). The median rectal V70 was 9.2%
      (2.5-15.4). The median bladder V50, V80, and mean dose were 12.4% (3.7-27.1), 3.5
      cm3 (0-7.1), and 14.9 Gy (RBE) (4.6-37.8), respectively. The median contralateral
      femur head V45 and max dose were 0.01 cm3 (0-16.6) and 43.7 Gy (RBE) (15.6-52.5),
      respectively. The incidence of acute Grade 2 urinary toxicity was 40%. There were
      no Grade>=3 urinary toxicities. There was one patient who developed late Grade 2
      rectal proctitis, with no other cases of acute or late >=Grade 2 gastrointestinal
      toxicity. Grade 2 erectile dysfunction occurred in two patients (11.1%). Mild hip
      pain was experienced by five patients (25%). There were no cases of hip fracture.
      CONCLUSION: PBT for prostate cancer utilizing anterior oblique beam trajectories
      is feasible with favorable dosimetry and acceptable toxicity. Further follow-up
      is needed to assess for long-term outcomes and toxicities.

PMID- 25591938
TI  - Why is intravenous chemotherapy cancelled and how often. Could it be prevented? A
      prospective analysis of all planned and given intravenous anti-tumor treatments
      at the Department of Oncology, Karolinska University Hospital, Stockholm during
      one month.
AB  - BACKGROUND: Chemotherapy and targeted drugs are important tools in the treatment
      of malignant diseases. A number of the planned treatments are cancelled late
      which is a great challenge for the clinic to minimize in order to prevent the
      risk for misused resources. The aim of this study was to analyze the frequency
      and reasons for late (<48 hours) cancellations and also to get an overview of all
      intravenous medical anti-cancer treatment at the clinic. MATERIAL AND METHODS:
      During four weeks in October 2010 all patients with intravenously administered
      chemotherapy and/or targeted drugs were registered at the Department of Oncology,
      Karolinska University Hospital. The survey comprehends the vast majority of all
      such treatment for solid tumors in adult patients in the Stockholm region with
      two million inhabitants. All bookings and late cancellations including their
      reasons were recorded. Diagnoses, treatment indication, line of treatment and
      survival, in particular short term survival, were analyzed. RESULTS: Almost 3000
      bookings for 1460 patients were included and 13% were cancelled late. Patient
      detoriation was the dominating cause for late cancellation in patients with
      palliative treatment (59%), while hematological toxicity was most common in the
      adjuvant group (42%). The most common treatment indication was palliative (62%).
      Of the palliative treatments, 95% where given in the first to third treatment
      line. Breast cancer (31.9%) and colorectal cancer (29.9%) were the two most
      common diagnoses. Seventy-one patients (4.9%) died within two months after the
      treatment. CONCLUSION: A more careful selection and monitoring of the patients
      might reduce the number of late cancellations due to patient detoriation. To
      record performance status (PS) as a routine for all patients might be helpful in
      that process. If the number of late cancellations could be reduced, resources at
      the clinic could be used more efficiently.

PMID- 25591941
TI  - [In Process Citation].
AB  - Inflammation of bone is caused either by bacterial infection or occasionally by
      physical stimulus. Primary chronic osteomyelitis of mandibular bone is a chronic
      inflammation of an unknown cause. Pain, swelling, limited mouth opening, regional
      lymphadenopathy and hypaesthesia are clinical symptoms at initial presentation.
      Results of biopsy, computed tomography and scintigraphy reveal the diagnosis of a
      primary chronic osteomyelitis. Its management is long-term antibiotic therapy,
      hyperbaric oxygen and surgical therapy, even bisphophonate treatement may be a
      good option. The case report presents a primary progressive chronic osteomyelitis
      of the manibular bone of a ten year old boy. Clinical and radiological signs are
      discussed as well as diagnosis, management and follow-up. 

PMID- 25591940
TI  - The Arabidopsis alkaline ceramidase TOD1 is a key turgor pressure regulator in
      plant cells.
AB  - Turgor pressure plays pivotal roles in the growth and movement of walled cells
      that make up plants and fungi. However, the molecular mechanisms regulating
      turgor pressure and the coordination between turgor pressure and cell wall
      remodelling for cell growth remain poorly understood. Here, we report the
      characterization of Arabidopsis TurgOr regulation Defect 1 (TOD1), which is
      preferentially expressed in pollen tubes and silique guard cells. We demonstrate
      that TOD1 is a Golgi-localized alkaline ceramidase. tod1 mutant pollen tubes have
      higher turgor than wild type and show growth retardation both in pistils and in
      agarose medium. In addition, tod1 guard cells are insensitive to abscisic acid
      (ABA)-induced stomatal closure, whereas sphingosine-1-phosphate, a putative
      downstream component of ABA signalling and product of alkaline ceramidases,
      promotes closure in both wild type and tod1. Our data suggest that TOD1 acts in
      turgor pressure regulation in both guard cells and pollen tubes. 

PMID- 25591942
TI  - Testing the impact of virus importation rates and future climate change on dengue
      activity in Malaysia using a mechanistic entomology and disease model.
AB  - We aimed to reparameterize and validate an existing dengue model, comprising an
      entomological component (CIMSiM) and a disease component (DENSiM) for application
      in Malaysia. With the model we aimed to measure the effect of importation rate on
      dengue incidence, and to determine the potential impact of moderate climate
      change (a 1  degrees C temperature increase) on dengue activity. Dengue models
      (comprising CIMSiM and DENSiM) were reparameterized for a simulated Malaysian
      village of 10 000 people, and validated against monthly dengue case data from the
      district of Petaling Jaya in the state of Selangor. Simulations were also
      performed for 2008-2012 for variable virus importation rates (ranging from 1 to
      25 per week) and dengue incidence determined. Dengue incidence in the period 2010
      2012 was modelled, twice, with observed daily weather and with a 1  degrees C
      increase, the latter to simulate moderate climate change. Strong concordance
      between simulated and observed monthly dengue cases was observed (up to r =
      0.72). There was a linear relationship between importation and incidence.
      However, a doubling of dengue importation did not equate to a doubling of dengue
      activity. The largest individual dengue outbreak was observed with the lowest
      dengue importation rate. Moderate climate change resulted in an overall decrease
      in dengue activity over a 3-year period, linked to high human seroprevalence
      early on in the simulation. Our results suggest that moderate reductions in
      importation with control programmes may not reduce the frequency of large
      outbreaks. Moderate increases in temperature do not necessarily lead to greater
      dengue incidence. 

PMID- 25591943
TI  - Epigallocatechin gallate inhibits human tongue carcinoma cells via HK2-mediated
      glycolysis.
AB  - Epigallocatechin gallate (EGCG), one of the major catechins found in green tea,
      was suggested to play a role as a chemopreventive agent in various human cancer
      models. In this study, we reported that EGCG has a profound antitumor effect on
      human tongue carcinoma cells by directly regulating glycolysis. EGCG dose
      dependently inhibited anchorage-independent growth and short-term EGCG exposure
      substantially decreased EGF-induced EGF receptor (EGFR), Akt and ERK1/2
      activation, as well as the downregulation of hexokinase 2 (HK2). Furthermore,
      inhibition of EGCG-mediated HK2 expression was involved in Akt, but not in ERK1/2
      signaling pathway suppression. Overexpression of constitutively activated Akt1
      rescued inhibition of EGCG-induced glycolysis. Moreover, EGCG inhibited HK2
      expression on mitochondrial outer membrane and induced apoptosis. In summary, the
      results suggested that EGCG or a related analogue, may have a role in the
      management of human tongue carcinoma.

PMID- 25591944
TI  - Angle- and strain-independent coloured free-standing films incorporating non
      spherical colloidal photonic crystals.
AB  - Colloidal photonic crystals (CPCs) provide a convenient way to generate
      structural colour with high stability against degradation under environmental
      factors. For a number of applications including flexible electronic and energy
      devices, it is important to generate flexible structural colour that maintains
      its colour regardless of the angle of observation and the extent of mechanical
      deformation. However, it is challenging to simultaneously achieve these goals
      because anisotropy in typical CPC structures (e.g., CPC films) tends to lead to
      angle-dependent photonic properties and also changes in the lattice constant due
      to mechanical deformation lead to changes in the photonic properties of CPCs. To
      overcome these challenges, we present a means of fabricating large-area free
      standing films of CPC structures that exhibit angle- and strain-independent
      photonic characteristics. First, monodisperse double emulsions encapsulating
      colloidal crystal arrays are prepared using a microfluidic device. By inducing
      crystallization of highly charged polystyrene particles in the core of double
      emulsions using osmotic annealing, we generate angle independent colloidal
      photonic crystal (CPC) supraparticles. Moreover, the shape and crystallinity of
      the CPC supraparticles can be tuned by changing the concentration of salt in the
      solution used for osmotic annealing. Subsequently, an array of CPC supraparticles
      is embedded inside an elastomeric matrix to form a flexible free-standing film,
      which exhibits structural colours that are independent of viewing angles and
      externally applied strain. 

PMID- 25591946
TI  - Is it a stroke?

PMID- 25591945
TI  - Barriers and facilitators related to use of prenatal care by inner-city women:
      perceptions of health care providers.
AB  - BACKGROUND: Socioeconomic disparities in the use of prenatal care (PNC) exist
      even where care is universally available and publicly funded. Few studies have
      sought the perspectives of health care providers to understand and address this
      problem. The purpose of this study was to elicit the experiential knowledge of
      PNC providers in inner-city Winnipeg, Canada regarding their perceptions of the
      barriers and facilitators to PNC for the clients they serve and their suggestions
      on how PNC services might be improved to reduce disparities in utilization.
      METHODS: A descriptive exploratory qualitative design was used. Semi-structured
      interviews were conducted with 24 health care providers serving women in inner
      city neighborhoods with high rates of inadequate PNC. Content analysis was used
      to code the interviews based on broad categories (barriers, facilitators,
      suggestions). Emerging themes and subthemes were then developed and revised
      through the use of comparative analysis. RESULTS: Many of the barriers identified
      related to personal challenges faced by inner-city women (e.g., child care,
      transportation, addictions, lack of support). Other barriers related to aspects
      of service provision: caregiver qualities (lack of time, negative behaviors),
      health system barriers (shortage of providers), and program/service
      characteristics (distance, long waits, short visits). Suggestions to improve care
      mirrored the facilitators identified and included ideas to make PNC more
      accessible and convenient, and more responsive to the complex needs of this
      population. CONCLUSIONS: The broad scope of our findings reflects a socio
      ecological approach to understanding the many determinants that influence whether
      or not inner-city women use PNC services. A shift to community-based PNC
      supported by a multidisciplinary team and expanded midwifery services has
      potential to address many of the barriers identified in our study.

PMID- 25591947
TI  - Does somatostatin or gastric inhibitory peptide receptor expression correlate
      with tumor grade and stage in gut neuroendocrine tumors?
AB  - BACKGROUND/AIMS: Important characteristics of neuroendocrine neoplasms (NEN) for
      prognosis and therapeutic decisions are the MIB-1 proliferative index (tumor
      grade) and tumor stage. Moreover, these tumors express peptide hormone receptors
      like somatostatin and gastric inhibitory peptide (GIP) receptors which represent
      important established and potential future targets, respectively, for molecular
      imaging and radiotherapy. However, the interrelation between tumor proliferation,
      stage, and peptide receptor amounts has never been assessed. METHODS: In 114
      gastrointestinal and bronchopulmonary NEN, the proliferative rate assessed with
      MIB-1 immunohistochemistry and tumor stage were compared with the somatostatin
      type 2 receptor (sst2) and GIP receptor expression measured quantitatively with
      in vitro receptor autoradiography. RESULTS: NEN generally showed high sst2 and
      GIP receptor expression. GIP receptor but not sst2 expression correlated with the
      MIB-1 index. GIP receptor levels gradually increased in a subset of insulinomas
      and nonfunctioning pancreatic NEN, and decreased in ileal and bronchopulmonary
      NEN with increasing MIB-1 rate. MIB-1 levels were identified, above which GIP
      receptor levels were consistently high or low. These MIB-1 levels were clearly
      different from those defining tumor grade. In grade 3 NEN, GIP receptor levels
      were always low, while sst2 levels were variable and sometimes extremely high.
      Conversely, sst2 expression correlated more frequently with tumor stage than GIP
      receptor expression, with metastasized NEN showing higher sst2 levels than
      localized tumors. CONCLUSIONS: sst2, a clinically crucial molecular target, shows
      variable and unpredictable expression in NEN irrespective of tumor grade.
      Therefore, each NEN should be tested for sst2 if clinical applications with
      somatostatin analogs are considered. Conversely, the potential future role of GIP
      receptors as molecular targets in NEN may be dependent on the MIB-1 level.

PMID- 25591948
TI  - Fecal calprotectin in patients with suspected small bowel disease--a selection
      tool for small bowel capsule endoscopy?
AB  - OBJECTIVE: Fecal calprotectin (FC) has been proposed as a selection tool for
      gastrointestinal examinations, but the use of FC in the diagnosis of small bowel
      disease in particular is less studied. The aim of this study was to assess if FC
      could be used to predict findings on small bowel capsule endoscopy (SBCE).
      MATERIAL AND METHODS: We retrospectively collected FC values, SBCE findings and
      clinical data in 161 patients with suspected small bowel disease referred for
      SBCE. Findings on SBCE were correlated with FC levels and the diagnostic value of
      FC was assessed. RESULTS: Of the 161 patients, 37.3% had a positive FC and 29.8%
      had a finding on SBCE. Overall there was a significant difference in FC values
      between patients with any finding on SBCE and patients with a normal SBCE, but
      patients with ulcers/erosions was the only subgroup of patients with FC values
      significantly higher than patients with a normal SBCE. The proportion of patients
      with findings on SBCE increased with increasing FC value. A positive FC (>=50
      mg/kg) had a sensitivity, specificity, positive predictive value and negative
      predictive value of 54.2%, 69.9%, 43.3% and 78.2%, respectively, for predicting
      findings on SBCE. CONCLUSIONS: FC alone cannot be used as a selection tool for
      SBCE in patients with suspected small bowel disease in a specialist setting.
      However, a high FC value implies a higher probability of finding significant
      pathology on SBCE, and thus strengthens the indication for performing the
      examination.

PMID- 25591949
TI  - Health-Related Quality of Life in adolescent survivors of burns: Agreement on
      self-reported and mothers' and fathers' perspectives.
AB  - AIM: This study examined the agreement on self-reported Health-Related Quality of
      Life (HRQOL) between adolescents with burns and their mother's and father's
      observation at 6 and 18 months after the burn. Moreover, factors potentially
      influencing discrepancies between the adolescent and proxy reports were examined.
      METHODS: Children with burns (11-18 years old) and their mother and father were
      invited to participate. A total of 54 adolescents aged 11 years or older filled
      out the American Burn Association/Shriners Hospitals for Children Burn Outcomes
      Questionnaire (BOQ). Descriptive and correlational analyses were performed.
      RESULTS: The physical functioning scores showed to be optimal in almost all
      participants (99%) and across the three informants. Adolescents reported better
      functioning than their fathers and mothers on most of the scales. On average the
      correlations between self-reports and proxy reports were moderate to good. Higher
      parental traumatic stress scores were linked to less favorable parent-reported
      burn outcomes. CONCLUSION: Overall, this study showed that a large proportion of
      the parents had similar views on the adolescents physical functioning, but
      disparities emerged also, mainly in psychosocial scales. The discrepancies
      between self- and parent reports should be discussed when they have a role in
      treatment decisions. Preferably, besides parent-reports, adolescents' self
      reports should be included in clinical assessments and treatment decisions, as
      parental traumatic stress symptoms are a possible factor influencing parental
      observations.

PMID- 25591950
TI  - BMI-specific waist circumference is better than skinfolds for health-risk
      determination in the general population.
AB  - Distribution of fat is important when considering health risk; however, the value
      added from skinfold measurements (SKF) when using body mass index (BMI) refined
      by waist circumference (WC) is not well understood. The purpose of this study was
      to assess the utility of SKF compared with WC in determination of health risk in
      the general population. Data from the Canadian Health Measures Survey (cycles 1
      and 2; N = 5217) were used. Health outcomes included directly measured blood
      pressure, cholesterol, glycated haemoglobin, lung function, self-reported health,
      and chronic conditions. Technical errors of measurements (TEM), sensitivity, and
      specificity analysis and linear regressions were conducted. Data indicated that
      TEM for SKF was above the acceptable 5% in most age and sex categories.
      Sensitivity and specificity of chronic conditions was not improved with the
      inclusion of SKF in models containing WC (in those aged 45-69 years) and SKF did
      not explain any additional variance in regression models containing WC. Health
      outcomes for those in the normal weight and overweight BMI category were
      significantly worse in those classified as high risk based on WC, whereas SKF did
      not consistently discriminate risk. In conclusion, evidence-based WC cut-points
      were shown to identify health risk, particularly in normal weight and overweight
      individuals. Thus, BMI refined by WC appears to be more appropriate than SKF for
      assessment of body composition when determining health risk in the general
      population. 

PMID- 25591951
TI  - Interpolyelectrolyte complexes of Eudragit(r) EPO with hypromellose acetate
      succinate and Eudragit(r) EPO with hypromellose phthalate as potential carriers
      for oral controlled drug delivery.
AB  - The objective of this study was to compare a novel controlled release tablet
      formulation based on interpolyelectrolyte complex (PEC). Interpolymer
      interactions between the countercharged polymers like Eudragit(r) EPO
      (polycation) and hypromellose acetate succinate (polyanion) and Eudragit(r) EPO
      and hypromellose phthalate (polyanion) were investigated with a view to their use
      in per oral controlled release drug delivery systems. The formation of inter
      macromolecular ionic bonds between cationic polymer and anionic polymer was
      investigated using Fourier transform infrared (FT-IR) spectroscopy and
      differential scanning calorimetry. The FT-IR spectra of the tested polymeric
      matrices are characterized by visible changes in the observed IR region
      indicating the interaction between chains of two oppositely charged copolymers.
      The performance of the in situ formed PEC as a matrix for controlled release of
      drugs was evaluated, using acetaminophen as a model drug. The dissolution data of
      these matrices were fitted to different dissolution models. It was found that
      drug release followed zero-order kinetics and was controlled by the superposition
      of the diffusion and erosion. These profiles could be controlled by conveniently
      modifying the proportion of the polymer ratio, polymer type, and polymer
      concentration the in the tablets. 

PMID- 25591952
TI  - Development and evaluation of new microemulsion-based hydrogel formulations for
      topical delivery of fluconazole.
AB  - The aim of the present investigation was to develop and evaluate microemulsion
      loaded hydrogels (MEHs) for the topical delivery of fluconazole (FZ). The
      solubility of FZ in oils, surfactants and cosurfactants was evaluated to identify
      the components of the microemulsion. The pseudo-ternary phase diagrams were
      constructed using the novel phase diagram by micro-plate dilution method.
      Carbopol EDT 2020 was used to convert FZ-loaded microemulsions into gel form
      without affecting their structure. The selected microemulsions were assessed for
      globule size, zeta potential and polidispersity index. Besides this, the
      microemulsion-loaded hydrogel (MEH) formulations were evaluated for drug content,
      pH, rheological properties and in vitro drug release through synthetic membrane
      and excised pig ear skin in comparison with a conventional hydrogel. The
      optimised MEH FZ formulations consisting of FZ 2%, Transcutol P 11.5% and 11%,
      respectively, as oil phase, Lansurf SML 20-propyleneglycol 52% and 50%,
      respectively, as surfactant-cosurfactant (2:1), Carbopol EDT 2020 1.5% as gelling
      agent and water 34.5% and 37%, respectively, showed highest flux values and high
      release rate values, and furthermore, they had low surfactant content. The in
      vitro FZ permeation through synthetic membrane and excised pig ear skin from the
      studied MEHs was best described by the zero-order and first-order models.
      Finally, the optimised MEH FZ formulations showed similar or slightly higher
      antifungal activity as compared to that of conventional hydrogel and Nizoral(r)
      cream, respectively. The results suggest the potential use of developed MEHs as
      vehicles for topical delivery of FZ, encouraging further in vitro and in vivo
      evaluation. 

PMID- 25591953
TI  - A novel topical targeting system of caffeine microemulsion for inhibiting UVB
      induced skin tumor: characterization, optimization, and evaluation.
AB  - The purpose of the present study was to develop an optimal microemulsion (ME)
      formulation as topical nanocarrier of caffeine (CAF) to enhance CAF skin
      retention and subsequently improve its therapeutic effect on UVB-induced skin
      carcinogenesis. The pseudo-ternary phase diagram was developed composing of
      Labrafil M 1944 CS as oil phase, Cremophor EL as surfactant, tetraglycol as
      cosurfactant, and water. Four ME formulations at water content of 50, 60, 70, and
      80% were prepared along the water dilution line of oil to surfactant ratio of 1:3
      and characterized in terms of morphology, droplet size, and electric
      conductivity. A gel at the same drug loads (1%, w/w) was used as control. Ex vivo
      skin permeation studies were conducted for ME optimization. The optimized
      formulation (ME4) was composed of 5% (w/w) Labrafil M 1944 CS, 15% (w/w) Smix
      (2/1, Cremophor EL and tetraglycol), and 80% (w/w) aqueous phase. The skin
      location amount of CAF from ME4 was nearly 3-fold higher than control (P < 0.05)
      with improved permeated amount through the skin. The skin targeting localization
      of hydrophilic substance from ME4 was further visualized through fluorescent
      labeled ME by a confocal laser scanning microscope. In pharmacodynamics studies,
      CAF-loaded ME4 was superior in terms of increasing apoptotic sunburn cells (P <
      0.05) as compared with control. Overall results suggested that the ME4 might be a
      promising vehicle for the topical delivery of CAF. 

PMID- 25591954
TI  - Impact of S-1 plus Cisplatin Neoadjuvant Chemotherapy on Scirrhous Gastric
      Cancer.
AB  - OBJECTIVE: This retrospective study aimed to address the therapeutic outcome for
      scirrhous gastric cancer patients by evaluating the effect of neoadjuvant
      chemotherapy prior to gastrectomy. METHODS: Two cycles of a 3-week regimen of
      fluoropyrimidine S-1 (40 mg/m(2), orally, twice daily), together with cisplatin
      (60 mg/m(2), intravenously, day 8), were administered to patients, separated by a
      2-week rest period. Surgery was performed 3 weeks later in the neoadjuvant group
      (n = 27). We retrospectively evaluated overall survival and prognostic factors in
      these patients. RESULTS: Univariate analysis showed that positive lavage cytology
      indicated significantly worse prognoses. In the 15 patients who also underwent
      curative gastrectomies after S-1 plus cisplatin chemotherapy, the pathological
      response grade was a significant prognostic factor for 5-year survival.
      Additionally, lymph node metastasis tended to be an adverse prognostic factor.
      CONCLUSION: After S-1 plus cisplatin neoadjuvant chemotherapy, a grade 2-3
      pathological response may predict favorable outcomes in scirrhous gastric cancer
      patients receiving curative gastrectomy, but further studies are needed to
      confirm these results.

PMID- 25591955
TI  - Angiotensin II-induced Egr-1 expression is suppressed by peroxisome proliferator
      activated receptor-gamma ligand 15d-PGJ2 in macrophages.
AB  - BACKGROUND/AIMS: Angiotensin II (Ang II) plays a critical role in regulating
      vascular inflammatory diseases, such as atherosclerosis and hypertension. Early
      growth response-1 (Egr-1) is an immediate early gene that acts as a master switch
      for the inflammatory response. However, the role of Ang II in regulating Egr-1
      expression in macrophages, and the effect of peroxisome proliferators-activated
      receptor-gamma (PPAR-gamma) ligand 15d-PGJ2 in this process remain to be
      investigated. METHODS AND RESULTS: We showed that Ang II significantly up
      regulated the expression of Egr-1 in RAW264.7 macrophages, and this effect was
      markedly attenuated by Eprosartan (an AT1R blocker), SP600125 (a JNK-specific
      inhibitor) and PD98059 (an ERK-specific inhibitor). Moreover, treatment of
      macrophages with 15d-PGJ2, a natural PPAR-gamma ligand, significantly reduced Ang
      II-induced expression of Egr-1 and its inflammatory gene targets (IL-1beta, TNF
      alpha, TGF-beta, MCP-1 and ICAM-1) through PPAR-gamma activation and ROS
      formation. In addition, 15d-PGJ2 treatment markedly inhibited Ang II-induced
      macrophage migration and proliferation. CONCLUSIONS: This study for the first
      time demonstrates that Ang II can induce the expression of Egr-1 via AT1R/JNK and
      ERK signaling pathways. Activation of PPAR-gamma by 15d-PGJ2 suppresses Egr-1
      mediated proinflammatory response, and may be a novel therapeutic strategy for
      treatment of vascular inflammatory diseases.

PMID- 25591956
TI  - Intracellular accumulation and immunological properties of fluorescent gold
      nanoclusters in human dendritic cells.
AB  - We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (? <
      3 nm) stabilized by different ligands on the intracellular accumulation and
      immune response of human derived-monocyte dendritic cells (DCs). Results indicate
      that the high uptake efficiency of Au NCs is strongly related to their small size
      and to the nature of the ligand, with zwitterionic ligands being more effective
      than PEGylated ones. Evidence from flow cytometry and microscopy demonstrate time
      and concentration-dependent Au NCs internalization by endocytic pathway(s)
      involving amorphous and laminar organelles, while maintaining their discrete size
      and photoluminescence properties. The uptake of zwitterionic ligand-stabilized Au
      NCs induced very low cytotoxicity and a strong immunosuppressive response
      (Th1/Treg pattern), associated with a DC maturation state. This behavior
      contrasts to the effect of bigger particles (~12 nm size) which induced a
      cytotoxic response involving Natural Killer (CD56) cells. Overall, this study
      stresses the critical importance of particle size and ligand type on the
      immunostimulation of DCs and highlights the remarkable potential of this new
      class of nanomaterial as a novel vaccine platform. 

PMID- 25591957
TI  - Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune
      camouflage.
AB  - We investigated the immune camouflage effects of methoxy polyethylene glycol
      succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel
      approach for reducing corneal antigenicity, thereby decreasing corneal graft
      rejection. Importantly, this approach did not alter normal local immunity.
      Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could
      shield major histocompatibility antigen class I molecules (RT1-A) of corneal
      grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic
      lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co
      cultured with autologous corneal grafts or untreated corneal grafts and PEGylated
      grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin
      donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD
      group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower
      in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD
      rats with corneal neovascularisation were used as recipients for high-risk
      corneal transplantation and were randomly divided into four groups: autologous
      control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The
      recipients received corneal grafts from Wistar rats. Corneal graft survival was
      prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG
      SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA
      could immunologically camouflage corneal antigens to prolong corneal grafts
      survival in high-risk transplantation. 

PMID- 25591958
TI  - Cell selective chitosan microparticles as injectable cell carriers for tissue
      regeneration.
AB  - The detection, isolation and sorting of cells holds an important role in cell
      therapy and regenerative medicine. Also, injectable systems have been explored
      for tissue regeneration in vivo, because it allows repairing complex shaped
      tissue defects through minimally invasive surgical procedures. Here we report the
      development of chitosan microparticles with a size of 115.8 MUm able to capture
      and expand a specific cell type that can also be regarded as an injectable
      biomaterial. Monoclonal antibodies against cell surface antigens specific to
      endothelial cells and stem cells were immobilized on the surface of the
      microparticles. Experimental results showed that particles bioconjugated with
      specific antibodies provide suitable surfaces to capture a target cell type and
      subsequent expansion of the captured cells. Primarily designed for an application
      in tissue engineering, three main challenges are accomplished with the herein
      presented microparticles: separation, scale-up expansion of specific cell type
      and successful use as an injectable system to form small tissue constructs in
      situ. 

PMID- 25591960
TI  - Synthetic beta-sheet forming peptide amphiphiles for treatment of fungal
      keratitis.
AB  - Fungal keratitis is a leading cause of ocular morbidity. It is frequently
      misdiagnosed as bacterial keratitis, causing a delay in proper treatment.
      Furthermore, due to the lack of safe and effective anti-fungal agents for
      clinical use, treatment of fugal keratitis remains a challenge. In recent years,
      antimicrobial peptides (AMPs) have received considerable attention as potent and
      broad-spectrum antimicrobial agents with the potential to overcome antibiotics
      resistance. We previously reported the design of short synthetic beta-sheet
      forming peptides (IKIK)2-NH2 and (IRIK)2-NH2 with excellent antimicrobial
      activities and selectivities against various clinically relevant microorganisms,
      including Gram-positive Staphylococcus epidermidis and Staphylococcus aureus,
      Gram-negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida
      albicans (C. albicans). In this study, we evaluated the application of the two
      most promising synthetic beta-sheet forming peptide candidates for in vivo fungal
      keratitis treatment in comparison with the commercially available amphotericin B.
      It was found that topical solutions of the designed peptides are safe, and as
      effective as the clinically used amphotericin B. Compared to the costly and
      unstable amphotericin B, (IKIK)2-NH2 and (IRIK)2-NH2 are water-soluble, less
      expensive and stable. Thus, the synthetic beta-sheet forming peptides are
      presented as promising candidates for the treatment of fungal keratitis. 

PMID- 25591959
TI  - Enhanced differentiation of neural progenitor cells into neurons of the
      mesencephalic dopaminergic subtype on topographical patterns.
AB  - Parkinson's disease (PD) is a neurodegenerative disease attributed to the loss of
      midbrain dopaminergic (DA) neurons. The current lack of predictive models for
      this disease has been hampered by the acquirement of robust cells, posing a major
      barrier to drug development. Differentiation of stem cells into subtype specific
      cells may be guided by appropriate topographical cues but the role of topography
      has hitherto not been well understood. We used a Multi-Architecture (MARC) chip
      with various topographical structures and identified three topographies, which
      generate DA neurons from murine hippocampal neural progenitor cells with the
      highest percentage of neuronal (beta-III-tubulin positive) and dopaminergic
      (tyrosine hydroxylase positive) populations. Analysis on single pattern
      structures showed that 2 MUm gratings with 2 MUm spacing and 2 MUm height (2 MUm
      gratings) and 2 MUm gratings with hierarchical structure produced cells with the
      highest gene expression of TH and PITX3, with the longest neurite and highest
      percentage of alignment. Quantitative image analysis showed the 2 MUm gratings
      produced cells with the highest expression of pituitary homeobox 3 (PITX3), LIM
      homeobox transcription factor 1 alpha (LMX1a), aldehyde dehydrogenase 1 family
      member A1 (ALDH1a1) and microtubule associated protein 2 (MAP2), as compared to
      nano-gratings and unpatterned controls. These patterns also enhance DA neuron
      differentiation on different substrate rigidities, as seen on both poly
      dimethylsiloxane (PDMS) and tissue culture polystyrene (TCPS) substrates. These
      results show the use of topographical influence for neuronal subtype
      specification, which could be translated into a wide range of clinical
      applications for PD. 

PMID- 25591961
TI  - Diversity in the utilization of glucose and lactate in synthetic mammalian
      myotubes generated by engineered configurations of MyoD and E12 in otherwise non
      differentiation growth conditions.
AB  - We previously used the expression of various combinations and configurations of
      MyoD and E12, two basic helix-loop-helix transcription factors (TF), to produce
      populations of myotubes assuming distinct morphology, myofibrillar development
      and Ca2+ dynamics, from mammalian C2C12 myoblasts in non-differentiation growth
      conditions. Here, we assessed the synthetically generated myotubes in terms of
      energetics, otherwise necessary to sustain their mechanical output as bio
      actuators. We found that the myotubes exhibit changed expression of key
      regulators for the uptake and utilization of two major cellular fuels, glucose
      and lactate. Furthermore, while lactate transport was uniformly slowed in all the
      populations of myotubes, glucose uptake and utilization were modified by
      particular TF configuration. Our approach allows the production of a class of
      biomaterials with predetermined energetics that could be applied in biorobotics,
      where fuel of choice could be used, and also in reparative medicine where, for
      example, particular population of myotubes could be additionally employed as
      glucose sinks to mitigate effects of secondary metabolic syndrome.

PMID- 25591962
TI  - Mitigation of hypertrophic scar contraction via an elastomeric biodegradable
      scaffold.
AB  - Hypertrophic scar (HSc) occurs in 40-70% of patients treated for third degree
      burn injuries. Current burn therapies rely upon the use of bioengineered skin
      equivalents (BSEs), which assist in wound healing but do not prevent HSc
      contraction. HSc contraction leads to formation of a fixed, inelastic skin
      deformity. We propose that BSEs should maintain their architecture in the wound
      bed throughout the remodeling phase of repair to prevent HSc contraction. In this
      work we study a degradable, elastomeric, randomly oriented, electrospun micro
      fibrous scaffold fabricated from the copolymer poly(l-lactide-co-epsilon
      caprolactone) (PLCL). PLCL scaffolds displayed appropriate elastomeric and
      tensile characteristics for implantation beneath a human skin graft. In vitro
      analysis using human dermal fibroblasts demonstrated that PLCL scaffolds
      decreased myofibroblast formation as compared to an in vitro HSc contraction
      model. Using a validated immune-competent murine HSc contraction model, we found
      that HSc contraction was significantly greater in animals treated with standard
      of care, Integra, as compared to those treated with collagen coated-PLCL (ccPLCL)
      scaffolds. Finally, wounds treated with ccPLCL were significantly less stiff than
      control wounds at d30 in vivo. Together, these data suggest that scaffolds which
      persist throughout the remodeling phase of repair may represent a clinically
      translatable method to prevent HSc contraction. 

PMID- 25591963
TI  - The influence of macro and trace elements on sperm quality.
AB  - The aim of this study was to examine the association between combined
      concentrations of macro and trace elements and markers of oxidative stress and
      antioxidative defense system function together with selected cytokine levels.
      Based on the combined medians of the seminal plasma levels of calcium, magnesium,
      zinc, copper, iron, and selenium, the study subjects (88 fertile male volunteers)
      were divided into the following two subgroups: the Me-L group (low level of
      metals) and the Me-H group (high level of metals). There was a tendency toward
      reduced motility in the Me-H group compared to that in the Me-L group. The total
      protein, albumin, and total oxidation status (TOS) levels were significantly
      higher in the Me-H group than in the Me-L group. The total superoxide dismutase
      (SOD), Mn-SOD, and CuZn-SOD, activity in spermatozoa were significantly lower in
      the Me-H group than in the Me-L group. In seminal plasma, the Mn-SOD activity was
      significantly higher in the Me-H group, whereas the CuZn-SOD activity was
      significantly lower. Additionally, the activity levels of glutathione peroxidase
      (GPx) and glutathione-S-transferase (GST) were lower in the Me-H group. The
      medians of IL-1beta, IL-10, and IL-12 were significantly higher in the Me-H group
      than in the Me-L group, whereas the medians of IL-2, IL-5, and IL-13 were
      significantly lower. Higher levels of macro and trace elements in the seminal
      plasma of fertile males may be associated with decreased motility. Higher levels
      of the examined metals are associated with elevated oxidative stress accompanied
      by decreased activities of some of the antioxidant enzymes and increased pro
      inflammatory cytokine levels. 

PMID- 25591965
TI  - Two-dye based arrayed primer extension for simultaneous multigene detection in
      lipid metabolism.
AB  - BACKGROUND: Cardiovascular disease (CVD) is one of the major causes of death
      worldwide. Numerous genetic risk factors in lipid metabolism, including mutations
      of LDLR, APOB, and PCSK9, as well as polymorphisms of CETP and APOE, have been
      found to associate with CVD. METHODS: In this study, a two-dye based arrayed
      primer extension (APEX) microarray assay for simultaneous multigene (LDLR, APOB,
      PCSK9, CETP, and APOE) detection was developed. The DNA templates, originating
      from 1 DNA sample of known genotype and 7 blind DNA samples, were amplified by
      uniplex PCR. RESULTS: Optimized conditions for the APEX reaction were determined
      to include a hybridization temperature of 55 degrees C and a DNA template size of
      50-150bp. The total assay including PCR, purification, fragmentation, APEX
      reaction, and image analysis could be performed in 6h. In total, 48 genotypes
      were identified among 8 individual DNA samples by APEX analysis. CONCLUSIONS: The
      data suggest that this APEX microarray offers a robust, fast, and versatile
      option for screening these genotypes in hypercholesterolemia patients.

PMID- 25591964
TI  - Simultaneous gas-chromatographic urinary measurement of sugar probes to assess
      intestinal permeability: use of time course analysis to optimize its use to
      assess regional gut permeability.
AB  - BACKGROUND: Measurement of intestinal permeability is important in several
      diseases but currently several methods are employed. We sought to: (1) develop a
      new GC based method to measure urinary mannitol, lactulose and sucralose to
      assess regional and total gut permeability; (2) analyze the kinetics of these
      sugars in the urine to determine which ratio is useful to represent intestinal
      permeability; and (3) determine whether age, gender, race and BMI impact these
      values. METHODS: Subjects drank a cocktail of sucrose, lactulose, mannitol and
      sucralose and these sugars were measured in the urine at 5, 12 and 24h with gas
      chromatography. RESULTS: Urinary mannitol exhibited significantly different
      kinetics than lactulose and sucralose which were similar to each other and varied
      little over the 24h. No permeability differences were observed for renal
      function, age, race, sex, or BMI. CONCLUSIONS: Our data do not support the use of
      the widely used L/M ratio as an accurate estimate of intestinal permeability. Our
      data support the use of: the sucralose/lactulose (S/M) ratio to measure: small
      intestine permeability (first 5h); small and large intestine (first 12h), and
      total gut permeability (24h). This was also found to be true in a Parkinson's
      disease model.

PMID- 25591966
TI  - Noninvasive monitoring of plasma L-dopa concentrations using sweat samples in
      Parkinson's disease.
AB  - BACKGROUND: L-dopa (l-3,4-dihydroxyphenylalanine) is commonly used for treating
      Parkinson's disease (PD). However, regardless of its prominent effect,
      therapeutic range of L-dopa narrows down with disease progression, which leads to
      development of motor complications including wearing off and dyskinesias. In
      addition, intestinal absorption of L-dopa is inversely correlated with the amount
      of oral protein intake, and shows intra- and inter-day variability. Hence,
      frequent monitoring of plasma L-dopa concentrations is beneficial, but frequent
      venipuncture imposes physical and psychological burdens on patients with PD.
      METHODS: We investigated the usefulness of sweat samples instead of plasma
      samples for monitoring L-dopa concentrations. With a monolithic silica disk
      packed spin column and the high-performance liquid chromatography-electrochemical
      detection system, L-dopa in sweat samples was successfully quantified and
      analyzed in 23 PD patients. RESULTS: We found that the Pearson's correlation
      coefficient of the plasma and sweat l-dopa concentrations was 0.678. Although the
      disease durations and severities were not correlated with the deviation of the
      actual sweat L-dopa concentrations from the fitted line, acquisition of the sweat
      samples under a stable condition was technically difficult in severely affected
      patients. The deviations may also be partly accounted for by skin permeability of
      L-dopa. CONCLUSIONS: Measuring L-dopa concentrations in sweat is suitable to get
      further insights into the L-dopa metabolism.

PMID- 25591967
TI  - A novel enzyme with spermine oxidase properties in bovine liver mitochondria:
      identification and kinetic characterization.
AB  - The uptake of spermine into mammalian mitochondria indicated the need to identify
      its catabolic pathway in these organelles. Bovine liver mitochondria were
      therefore purified and their capacity for natural polyamine uptake was verified.
      A kinetic approach was then used to determine the presence of an MDL 72527
      sensitive enzyme with spermine oxidase activity in the matrix of bovine liver
      mitochondria. Western blot analysis of mitochondrial fractions and immunogold
      electron microscopy observations of purified mitochondria unequivocally confirmed
      the presence of a protein recognized by anti-spermine oxidase antibodies in the
      mitochondrial matrix. Preliminary kinetic characterization showed that spermine
      is the preferred substrate of this enzyme; lower activity was detected with
      spermidine and acetylated polyamines. Catalytic efficiency comparable to that of
      spermine was also found for 1-aminododecane. The considerable effect of ionic
      strength on the Vmax/KM ratio suggested the presence of more than one negatively
      charged zone inside the active site cavity of this mitochondrial enzyme, which is
      probably involved in the docking of positively charged substrates. These findings
      indicate that the bovine liver mitochondrial matrix contains an enzyme belonging
      to the spermine oxidase class. Because H2O2 is generated by spermine oxidase
      activity, the possible involvement of the latter as an important signaling
      transducer under both physiological and pathological conditions should be
      considered. 

PMID- 25591968
TI  - Protective role of quercetin against cisplatin-induced hair cell damage in
      zebrafish embryos.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the protective
      effects of quercetin on cisplatin-induced hair cell damage in transgenic
      zebrafish embryos. MATERIALS AND METHODS: Five days postfertilization zebrafish
      embryos were exposed to 1 mM cisplatin and quercetin at 10, 50, 100, or 200 MUM
      for 4 h. Hair cells within neuromasts of the supraorbital, otic, and occipital
      lateral lines were analyzed by fluorescent microscopy (n = 10). Survival of hair
      cells was calculated as the average number of hair cells in the control group
      that were not exposed to cisplatin. Ultrastructural changes were evaluated using
      scanning electron microscopy. RESULTS: Hair cell damage in neuromasts was
      decreased by co-treatment of quercetin and cisplatin (quercetin 100 MUM: 8.6 +/-
      1.1 cells; 1 mM cisplatin only: 5.0 +/- 0.5 cells; n = 10, p < 0.05); apoptosis
      of hair cells examined by special stain was also decreased by quercetin. The
      ultrastructure of hair cells within neuromasts was preserved in zebrafish by the
      combination of quercetin (100 MUM) and cisplatin (1 mM). CONCLUSION: In
      conclusion, quercetin showed protective effects against cisplatin-induced
      toxicity in a zebrafish model. The results of this study suggest the possibility
      of a protective role of quercetin against cisplatin-induced apoptotic cell death
      in zebrafish.

PMID- 25591969
TI  - Clinical safety assessment of oral higenamine supplementation in healthy, young
      men.
AB  - OBJECTIVE: Higenamine, an herbal agent also known as norcoclaurine, is thought to
      stimulate beta-androgenic receptors and possess lipolytic activity. It is
      currently making its way into the dietary supplement market. To our knowledge, no
      studies have been conducted to determine the safety profile of oral higenamine
      when used alone and in conjunction with other commonly used lipolytic agents.
      METHODS: Forty-eight men were assigned to ingest either a placebo, higenamine,
      caffeine, or higenamine + caffeine + yohimbe bark extract daily for a period of 8
      weeks. Before and after 4 and 8 weeks of supplementation, the following variables
      were measured: resting respiratory rate, heart rate, blood pressure, urinalysis,
      complete blood count, metabolic panel, liver enzyme activity, and lipid panel.
      RESULTS: No interaction effects were noted for any variable (p > 0.05), with no
      changes of statistical significance occurring across time for any of the four
      conditions (p > 0.05). CONCLUSION: This is the first study to determine the
      safety profile of oral higenamine intake in human subjects. Our data indicate
      that 8 weeks of daily higenamine supplementation, either alone or in conjunction
      with caffeine and yohimbe bark extract, does not result in a statistically
      significant change in any of the measured outcome variables. Additional studies,
      inclusive of a larger sample size, are needed to extend these initial findings.

PMID- 25591970
TI  - Building a Career as a Delivery Science Researcher in a Changing Health Care
      Landscape.

PMID- 25591972
TI  - Fluorescent molecules as transceiver nanoantennas: the first practical and high
      rate information transfer over a nanoscale communication channel based on FRET.
AB  - Nanocommunications via Forster Resonance Energy Transfer (FRET) is a promising
      means of realising collaboration between photoactive nanomachines to implement
      advanced nanotechnology applications. The method is based on exchange of energy
      levels between fluorescent molecules by the FRET phenomenon which intrinsically
      provides a virtual nanocommunication link. In this work, further to the extensive
      theoretical studies, we demonstrate the first information transfer through a FRET
      based nanocommunication channel. We implement a digital communication system
      combining macroscale transceiver instruments and a bulk solution of fluorophore
      nanoantennas. The performance of the FRET-based Multiple-Input and Multiple
      Output (MIMO) nanocommunication channel between closely located mobile
      nanoantennas in the sample solution is evaluated in terms of Signal-to-Noise
      Ratio (SNR) and Bit Error Rate (BER) obtained for the transmission rates of 50
      kbps, 150 kbps and 250 kbps. The results of the performance evaluation are very
      promising for the development of high-rate and reliable molecular communication
      networks at nanoscale.

PMID- 25591971
TI  - The application of scanning near field optical imaging to the study of human
      sperm morphology.
AB  - BACKGROUND: The morphology of spermatozoa is a fundamental aspect to consider in
      fertilization, sperm pathology, assisted reproduction and contraception. Head,
      neck, midpiece, principal and terminal part of flagellum are the main sperm
      components to investigate for identifying morphological features and related
      anomalies. Recently, scanning near-field optical microscopy (SNOM), which belongs
      to the wide family of nanoscopic techniques, has opened up new routes for the
      investigation of biological systems. SNOM is the only technique able to provide
      simultaneously highly resolved topography and optical images with a resolution
      beyond the diffraction limit, typical of conventional optical microscopy. This
      offers the advantage to obtain complementary information about cell surface and
      cytoplasmatic structures. RESULTS: In this work human spermatozoa both healthy
      and with morphological anomalies are analyzed by SNOM, to demonstrate the
      potentiality of such approach in the visualization of sperm morphological
      details. The combination of SNOM topography with optical (reflection and
      transmission) images enables to examine typical topographic features of
      spermatozoa together with underlying cytoplasmic structures. Indeed the head
      shape and inner components as acrosome and nucleus, and the organization of
      mitochondria in the midpiece region are observed. Analogously for principal tract
      of the tail, the ridges and the columns are detected in the SNOM topography,
      while their internal arrangement can be observed in the corresponding SNOM
      optical transmission images, without requiring specific staining procedures or
      invasive protocols. CONCLUSIONS: Such findings demonstrate that SNOM represents a
      versatile and powerful tool to describe topographical and inner structural
      details of spermatozoa simultaneously. This analysis could be helpful for better
      characterizing several morphological anomalies, often related to sperm
      infertility, which cannot be examined by conventional techniques all together.

PMID- 25591973
TI  - Sarcopenia and critical illness: a deadly combination in the elderly.
AB  - Sarcopenia is the age-associated loss of lean skeletal muscle mass. It is the
      result of multiple physiologic derangements, ultimately resulting in an insidious
      functional decline. Frailty, the clinical manifestation of sarcopenia and
      physical infirmity, is associated with significant morbidity and mortality in the
      elderly population. The underlying pathology results in a disruption of the
      individual's ability to tolerate internal and external stressors such as injury
      or illness. This infirmity results in a markedly increased risk of falls and
      subsequent morbidity and mortality from the resulting traumatic injury, as well
      as an inability to recover from medical insults, resulting in critical illness.
      The increasing prevalence of sarcopenia and critical illness in the elderly has
      resulted in a deadly intersection of disease processes. The lethality of this
      combination appears to be the result of altered muscle metabolism, decreased
      mitochondrial energetics needed to survive critical illness, and a chronically
      activated catabolic state likely mediated by tumor necrosis factor-alpha.
      Furthermore, these underlying derangements are independently associated with an
      increased incidence of critical illness, resulting in a progressive downward
      spiral. Considerable evidence has been gathered supporting the role of aggressive
      nutrition support and physical therapy in improving outcomes. Critical care
      practitioners must consider sarcopenia and the resulting frailty phenotype a
      comorbid condition so that the targeted interventions can be instituted and
      research efforts focused. 

PMID- 25591974
TI  - Thiamine Deficiency in a Developed Country: Acute Lactic Acidosis in Two Neonates
      Due to Unsupplemented Parenteral Nutrition.
AB  - Thiamine is a water-soluble vitamin implicated in several metabolic processes.
      Its deficiency, due to prolonged parenteral nutrition without adequate vitamin
      supplementation, can lead to multiorgan failure characterized by cardiovascular
      impairment and metabolic acidosis refractory to bicarbonate administration. Only
      thiamine administration allows the remission of symptoms. We report 2 preterm
      infants with acute thiamine deficiency due to prolonged parenteral nutrition
      without adequate vitamin supplementation.

PMID- 25591975
TI  - A new rapid method for detecting epidermal growth factor receptor mutations in
      non-small cell lung cancer.
AB  - Mutations in the epidermal growth factor receptor (EGFR) gene are associated with
      a favorable clinical response to the EGFR tyrosine kinase inhibitors gefitinib
      and erlotinib in non-small cell lung cancer (NSCLC). We present here, a new
      method for the rapid detection of the two most common EGFR mutations (delE746
      A750 and L858R) from clinical samples. The methodology involves the combination
      of newly designed mutation-specific primers and a novel real-time PCR machine
      with an innovative thermo-control mechanism that enables ultrarapid PCR. We
      evaluated this method using a cell mixture composed of various ratios of lung
      cancer cells harboring mutated or wild-type EGFR, lung cancer tissues obtained by
      surgery, and a cytology sample obtained by bronchoscopy from a lung cancer
      patient. In the cell mixture analysis, our method detected 0.1% of cells with
      delE746-A750 and 1% of cells with L858R among cells with wild-type EGFR. In 143
      lung cancer tissues, the result of this assay was concordant with those of direct
      sequencing in 138 samples. The five samples with discordant results were tested
      using a PCR-Invader assay and the result matched those of our method at 100%. We
      also successfully detected EGFR mutations in the lavage obtained from a lung
      cancer patient. The turnaround time for this method was <10 min, and all steps
      could be accomplished in <50 min after sample collection. Thus, our novel PCR
      method offers a rapid, simple, and less expensive test for EGFR mutations and can
      be applied as a point-of-care diagnostic test.

PMID- 25591976
TI  - Seroprevalence and risk factors of Toxoplasma gondii and Neospora caninum
      infections in small ruminants in China.
AB  - Little information is available about the seroprevalence of Toxoplasma gondii and
      Neospora caninum infections in sheep and goats in China. In the present
      investigation, the seroprevalence of T. gondii and N. caninum infections in sheep
      and goats were investigated in Qinghai province, China between January 2012 and
      June 2013. A total of 1250 serum samples (600 sheep and 650 goats) collected from
      8 administrative regions of Qinghai province, China were evaluated by enzyme
      linked immunosorbent assay for the detection of specific antibodies, and sera
      positive were subsequently confirmed with indirect fluorescent antibody test.
      Specific IgG against T. gondii were detected in 21.33% (95% confidence interval
      [CI]: 18.06-24.61%) (128/600) and 29.54% (95% CI: 26.03-33.05%) (192/650) and
      against N. caninum in 10.33% (95% CI: 7.9-12.77%) (62/600) and 7.23% (95% CI:
      5.24-9.22%) (47/650) of the sheep and goats, respectively. The risk factors
      significantly associated with T. gondii and N. caninum seroprevalence were the
      presence of cats and dogs, the pasturing system, the herd size, the hygiene in
      the farms. The results of the present survey indicate that T. gondii and N.
      caninum infections are highly prevalent in sheep and goats in Qinghai province,
      China. This is the first time that antibodies to N. caninum have been detected in
      sheep and goats in China. 

PMID- 25591977
TI  - Knowledge and behavior in an animal disease outbreak - Evidence from the item
      count technique in a case of African swine fever in Madagascar.
AB  - Pig production in Madagascar is not sufficient for domestic consumption.
      Unfortunately, African swine fever (ASF), which is a severe disease, is endemic
      in Madagascar and constitutes a constant threat for farmers. Therefore, ASF must
      be eradicated in order to guarantee the development of pig production. One of the
      main strategies in controlling ASF is stamping out which requires the farmers'
      collaboration in reporting cases or suspected cases. The objective of this study
      was to estimate the proportion of farmers who knowingly sell ASF-infected meat
      without reporting. Since selling ASF-infected meat is prohibited by the
      government, we used the item count technique (ICT), an indirect questioning
      technique appropriate for measuring the proportion of people engaged in sensitive
      behavior, for one subsample, while another subsample was asked directly whether
      they sell ASF-infected meat. Based on the ICT, approximately 73.2% of farmers who
      have experienced ASF sell the ASF-infected meat. This estimate was not
      statistically different from that obtained by direct questioning. In the 28% of
      interviewed farmers who believe ASF can affect humans, the ICT yielded a higher
      estimate than did direct questioning, indicating that pig farmers who sell ASF
      infected meat hide that fact because of their belief that infected meat might
      harm human consumers, not because of the law. The ICT was thus a suitable
      technique to address the problem of sensitive behavior. In the case of ASF
      outbreaks, the Malagasy government should enforce the law more strictly and
      provide compensation as incentive for reporting cases. 

PMID- 25591980
TI  - Leptin levels in Gaucher disease type I patients: A methodological approach.

PMID- 25591978
TI  - Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour
      immunity status.
AB  - OBJECTIVE: Evidence suggests protective effects of vitamin D and antitumour
      immunity on colorectal cancer risk. Immune cells in tumour microenvironment can
      convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1alpha,25-dihydroxyvitamin D3,
      which influences neoplastic and immune cells as an autocrine and paracrine
      factor. Thus, we hypothesised that the inverse association between vitamin D and
      colorectal cancer risk might be stronger for cancers with high-level immune
      response than those with low-level immune response. DESIGN: We designed a nested
      case-control study (318 rectal and colon carcinoma cases and 624 matched
      controls) within the Nurses' Health Study and Health Professionals Follow-up
      Study using molecular pathological epidemiology database. Multivariable
      conditional logistic regression was used to assess the association of plasma
      25(OH)D with tumour subtypes according to the degree of lymphocytic reaction,
      tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells),
      microsatellite instability or CpG island methylator phenotype. RESULTS: The
      association of plasma 25(OH)D with colorectal carcinoma differed by the degree of
      intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D
      was associated with lower risk of tumour with high-level reaction (comparing the
      highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend<0.001),
      but not risk of tumour with lower-level reaction (p for trend>0.50). A
      statistically non-significant difference was observed for the associations of
      25(OH)D with tumour subtypes according to CD3+ T cell density (p for
      heterogeneity=0.03; adjusted statistical significance level of alpha=0.006).
      CONCLUSIONS: High plasma 25(OH)D level is associated with lower risk of
      colorectal cancer with intense immune reaction, supporting a role of vitamin D in
      cancer immunoprevention through tumour-host interaction.

PMID- 25591981
TI  - Is the measurement of serum ischemia-modified albumin the best test to diagnose
      ovarian torsion?
AB  - AIM: The aim of this study is to evaluate the diagnostic value of serum oxidative
      stress marker levels (ischemia-modified albumin, IMA; malondialdehyde, MDA) and
      total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress
      index (OSI) levels that occur in ovarian torsion and to determine the threshold
      value of these markers in the diagnosis of ovarian torsion. METHODS: In this
      prospective case-control study, 34 women (the study group) with acute pelvic pain
      (20 with and 14 without ovarian torsion) and 40 control subjects were included.
      The diagnosis of ovarian torsion was confirmed with laparoscopy in all cases.
      Preoperative serum samples were collected in the study group. Serum oxidative
      stress marker levels (IMA and MDA) and TOS, TAS and OSI levels were measured.
      RESULTS: Serum MDA, TOS and IMA concentrations were significantly higher in women
      with ovarian torsion than in the healthy control group. However, serum TAS, TOS
      and OSI concentrations were significantly higher in women without ovarian torsion
      than within the healthy control group. Only IMA significantly distinguished
      patients with or without ovarian torsion. The best IMA value, according to the
      receiver operating characteristic curve, was 0.7045 absorbance units, with 90.00%
      sensitivity and 92.31% specificity. The patients in the ovarian torsion group had
      significantly lower serum TAS and OSI levels compared with patients without
      ovarian torsion. CONCLUSION: The elevated serum IMA levels with high sensitivity
      specificity values observed in women with ovarian torsion seem to have a
      potential role as a serum marker in the preoperative diagnosis of ovarian torsion
      in emergency settings.

PMID- 25591979
TI  - Antioxidant intake in paediatric oncology patients.
AB  - BACKGROUND & AIMS: Antioxidant intake can affect both free radical and the
      nutritional status of children receiving cancer treatment. The aim of this study
      was to investigate whether children with cancer met their antioxidant
      requirements. METHODS: A prospective observational study was performed at a
      single hospital in England from June 2008 to February 2010. Children with a solid
      tumour, lymphoma or leukaemia were included. Dietary intakes including 3 modes of
      feeding ('diet alone', 'diet + tube' feeding or 'diet + vitamin-mineral
      supplementation' (VMS)) were collected with an estimated food record (EFR) 1 and
      3 month post-diagnosis. Four and 24-hr food recalls were performed to validate
      the food records. RESULTS: Forty two children were included: 57% leukaemia or
      lymphoma and 43% solid tumours. Sixty seven percent underwent chemotherapy and
      33% a combination of therapies. In months 1 and 3, greater numbers of children
      achieved >=100% of requirements for 'diet + VMS' (p < 0.05) than for other
      feeding modes. However, considerable proportions of all feeding groups did not
      achieve 100% of the Recommended Nutrient Intake (RNI) for vitamin A, C, E,
      selenium and zinc. This was most marked in the 'diet alone' group. Significant
      proportions did not achieve the Lower Recommended Nutrient Intake (LRNI) for some
      antioxidants. The 'diet alone' group had the highest proportion not meeting LRNI
      for vitamin A (p << 0.001; 1st month) and zinc (p < 0.02; 3rd month). CONCLUSION:
      Inadequate antioxidant intake was observed in a significant proportion of cancer
      patients when feeding was not augmented in any way. More research is required to
      determine the clinical implications of these findings.

PMID- 25591982
TI  - Frontoethmoidal cephalocele: our experience of eleven cases managed surgically.
AB  - INTRODUCTION: Frontoethmoidal or sincipital cephaloceles are congenital
      malformations characterized by externalization of the meninges and/or brain
      tissue through a congenital bone defect between the frontal and ethmoid bones.
      These sincipital cephaloceles are very infrequent. While in developed countries
      the measures taken have brought about virtually zero frequency of this pathology,
      in our work environment these measures are virtually nonexistent, so that
      frontoethmoidal cephaloceles remain one of our concerns. AIM: To describe the
      particularity of the management of frontoethmoidal cephaloceles in our country.
      METHODS: This was a retrospective study carried out between January 1, 2007 and
      June 30, 2013. It concerned all cases of frontoethmoidal cephaloceles managed in
      the Neurosurgery Department of the University Hospital of Ouagadougou. RESULTS: A
      total of 11 patients (6 females and 5 males) were attended to in 6.5 years. The
      age of the patients ranged from 1 day to 12 years, and 8 patients (72.72%) were
      less than 4 months old; 1 case was diagnosed at antenatal ultrasound. Clinically,
      all cases consisted of congenital cephalic swelling of gradual increase. A CT
      scan was performed in all cases and an ultrasound of the associated mass was
      carried out in 2 cases. Transcranial approach was done for all patients with 3
      patients having had an incision of the mass to reduce redundant skin. The
      immediate postoperative course was favorable in 10 cases; 1 death was observed by
      cerebrospinal meningitis. We noted 1 case of recurrence. CONCLUSION: The surgical
      treatment of frontoethmoidal cephaloceles is complex, sometimes requiring a
      multidisciplinary team. However, early closing of the malformation before the
      appearance of important bone deformities can prevent maxillofacial surgery. The
      results of the surgery are satisfactory as regards the vital prognosis. However,
      the fear of a more or less long-term occurrence of psychomotor retardation and
      the complications of early surgery make the recommendation and emphasis of
      prevention our main concern.

PMID- 25591984
TI  - Metabolic risk in PCOS: phenotype and adiposity impact.
AB  - Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged
      women, with reproductive, cardiometabolic, and psychological features. The
      heterogeneity in insulin resistance, obesity, and cardiometabolic features has
      led to controversy on the independent contributions of PCOS status, diagnostic
      criteria, phenotype, and adiposity. It now appears that women with PCOS have an
      increased risk of insulin resistance and cardiometabolic features, which is
      independent of, but worsened by, adiposity and central adiposity, and is
      unrelated to reproductive phenotype. Obesity may be more prevalent in the more
      severe phenotypes, which suggests either an exacerbation of the reproductive
      features or a more likely diagnosis in overweight women with PCOS. Therefore, all
      women with PCOS should be targeted for prevention, screening, and management of
      cardiometabolic features. 

PMID- 25591983
TI  - Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer
      patients.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco
      regional recurrence and 5-year survival rates are about 50%. Identification of
      patients at high risk of recurrence will enable rigorous personalized post
      treatment management. Most novel biomarkers have failed translation for clinical
      use because of their limited successful validation in external patient cohorts.
      The aim of this study was to determine the prognostic significance of alterations
      in sub-cellular expression of S100A2, a pro-tumorigenic calcium binding protein,
      identified as a candidate biomarker in our proteomic analysis in OSCC and
      validation of its clinical utility in an external cohort. METHODS: In a
      retrospective study, immunohistochemical analysis of S100A2 was carried out in
      235 Indian OSCC (Test set) and 129 normal oral tissues, correlated with
      clinicopathological parameters and disease outcome over 122 months for OSCC
      patients following the REMARK criteria. The findings were validated in an
      external cohort (Validation set 115 Canadian OSCC and 51 normal tissues) and data
      analyzed using the R package. RESULTS: Significant increase in cytoplasmic and
      decrease in nuclear S100A2 expression was observed in OSCC in comparison with
      normal tissues. Cox multivariable regression analysis internally and externally
      validated cytoplasmic S100A2 association with tumor recurrence. Kaplan Meier
      analysis of patients stratified to high and low risk groups showed significantly
      different recurrence free survival (Test set- log rank test, p = 0.005, median
      survival 16 and 69 months respectively and Validation set - p < 0.00001, median
      survival 9.4 and 59.9 months respectively); 86% and 81% of patients who had
      recurrence were correctly stratified into the high risk group. Seventy percent
      and 81% patients stratified into low risk group did not show cancer recurrence
      within 1 year in Test and Validation sets. CONCLUSIONS: Our study provided
      clinical evidence for the potential of cytoplasmic S100A2 overexpression as a
      predictor of recurrence risk in OSCC patients. A unique translational aspect of
      our study is validation of S100A2 as prognostic marker in two independent cohorts
      (Canadian and Indian) suggesting this protein is likely to find widespread
      utility in clinical practice for identifying oral cancer patients at high risk of
      disease recurrence.

PMID- 25591987
TI  - BAFF knockout improves systemic inflammation via regulating adipose tissue
      distribution in high-fat diet-induced obesity.
AB  - Obesity is recognized as a chronic low-grade inflammatory state due to adipose
      tissue expansion being accompanied by an increase in the production of
      proinflammatory adipokines. Our group is the first to report that B-cell
      activating factor (BAFF) is produced from adipocytes and functions as a
      proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet
      induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10
      weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than
      in control mice, with a specific increase in the fat mass of the subcutaneous
      region rather than the abdominal region. Expression of lipogenic genes was
      examined by quantitative real-time PCR, and increased lipogenesis was observed in
      the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal
      adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in
      the downregulation of inflammatory gene expression in EAT, and more importantly,
      overall levels of inflammatory cytokines in the circulation were reduced in obese
      BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged
      SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with
      adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/
      ) mice contains antilipogenic and anti-inflammatory properties. Taken together,
      BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into
      subcutaneous regions. Understanding the mechanisms by which BAFF regulates
      obesity in a tissue-specific manner would provide therapeutic opportunities to
      target obesity-related chronic diseases. 

PMID- 25591986
TI  - Survivin - The inconvenient IAP.
AB  - Although technically a member of the Inhibitor of Apoptosis (IAP) gene family,
      survivin has consistently defied assumptions, refuted predictions and challenged
      paradigms. Despite its more than 5500 citations currently in Medline, the biology
      of survivin has remained fascinatingly complex, its exploitation in human
      disease, most notably cancer, tantalizing, and its regulation of cellular
      homeostasis unexpectedly far-reaching. An inconvenient outsider that resists
      schemes and dogmas, survivin continues to hold great promise to unlock
      fundamental circuitries of cellular functions in health and disease. 

PMID- 25591985
TI  - Power(2): the power of yeast genetics applied to the powerhouse of the cell.
AB  - The budding yeast Saccharomyces cerevisiae has served as a remarkable model
      organism for numerous seminal discoveries in biology. This paradigm extends to
      the mitochondria, a central hub for cellular metabolism, where studies in yeast
      have helped to reinvigorate the field and launch an exciting new era in
      mitochondrial biology. Here we discuss a few recent examples in which yeast
      research has laid a foundation for our understanding of evolutionarily conserved
      mitochondrial processes and functions, from key factors and pathways involved in
      the assembly of oxidative phosphorylation (OXPHOS) complexes to metabolite
      transport, lipid metabolism, and interorganelle communication. We also highlight
      new areas of yeast mitochondrial biology that are likely to aid in our
      understanding of the mitochondrial etiology of disease in the future. 

PMID- 25591989
TI  - Robust semi-automatic segmentation of pulmonary subsolid nodules in chest
      computed tomography scans.
AB  - The malignancy of lung nodules is most often detected by analyzing changes of the
      nodule diameter in follow-up scans. A recent study showed that comparing the
      volume or the mass of a nodule over time is much more significant than comparing
      the diameter. Since the survival rate is higher when the disease is still in an
      early stage it is important to detect the growth rate as soon as possible.
      However manual segmentation of a volume is time-consuming. Whereas there are
      several well evaluated methods for the segmentation of solid nodules, less work
      is done on subsolid nodules which actually show a higher malignancy rate than
      solid nodules. In this work we present a fast, semi-automatic method for
      segmentation of subsolid nodules. As minimal user interaction the method expects
      a user-drawn stroke on the largest diameter of the nodule. First, a threshold
      based region growing is performed based on intensity analysis of the nodule
      region and surrounding parenchyma. In the next step the chest wall is removed by
      a combination of a connected component analyses and convex hull calculation.
      Finally, attached vessels are detached by morphological operations. The method
      was evaluated on all nodules of the publicly available LIDC/IDRI database that
      were manually segmented and rated as non-solid or part-solid by four radiologists
      (Dataset 1) and three radiologists (Dataset 2). For these 59 nodules the Jaccard
      index for the agreement of the proposed method with the manual reference
      segmentations was 0.52/0.50 (Dataset 1/Dataset 2) compared to an inter-observer
      agreement of the manual segmentations of 0.54/0.58 (Dataset 1/Dataset 2).
      Furthermore, the inter-observer agreement using the proposed method (i.e.
      different input strokes) was analyzed and gave a Jaccard index of 0.74/0.74
      (Dataset 1/Dataset 2). The presented method provides satisfactory segmentation
      results with minimal observer effort in minimal time and can reduce the inter
      observer variability for segmentation of subsolid nodules in clinical routine.

PMID- 25591988
TI  - Amyloid precursor protein interaction network in human testis: sentinel proteins
      for male reproduction.
AB  - BACKGROUND: Amyloid precursor protein (APP) is widely recognized for playing a
      central role in Alzheimer's disease pathogenesis. Although APP is expressed in
      several tissues outside the human central nervous system, the functions of APP
      and its family members in other tissues are still poorly understood. APP is
      involved in several biological functions which might be potentially important for
      male fertility, such as cell adhesion, cell motility, signaling, and apoptosis.
      Furthermore, APP superfamily members are known to be associated with fertility.
      Knowledge on the protein networks of APP in human testis and spermatozoa will
      shed light on the function of APP in the male reproductive system. RESULTS: We
      performed a Yeast Two-Hybrid screen and a database search to study the
      interaction network of APP in human testis and sperm. To gain insights into the
      role of APP superfamily members in fertility, the study was extended to APP-like
      protein 2 (APLP2). We analyzed several topological properties of the APP
      interaction network and the biological and physiological properties of the
      proteins in the APP interaction network were also specified by gene ontologyand
      pathways analyses. We classified significant features related to the human male
      reproduction for the APP interacting proteins and identified modules of proteins
      with similar functional roles which may show cooperative behavior for male
      fertility. CONCLUSIONS: The present work provides the first report on the APP
      interactome in human testis. Our approach allowed the identification of novel
      interactions and recognition of key APP interacting proteins for male
      reproduction, particularly in sperm-oocyte interaction.

PMID- 25591991
TI  - From charge transfer to electron transfer in halogen-bonded complexes of
      electrophilic bromocarbons with halide anions.
AB  - Experimental and computational studies of the halogen-bonded complexes, [R-Br, X(
      )], of bromosubstituted electrophiles, R-Br, and halide anions, X(-), revealed
      that decrease of a gap between the frontier orbitals of interacting species led
      to reduction of the energy of the optical charge-transfer transition and to
      increase in the ground-state charge transfer (X(-) -> R-Br) in their associates.
      These variations were accompanied by weakening of the intramolecular, C-Br, and
      strengthening of the intermolecular, BrX(-), bonds. In the limit of the strongest
      electron donor-acceptor pairs, formation of the halogen-bonded complexes was
      followed by the oxidation of iodide to triiodide, which took place despite the
      fact that the I(-) -> R-Br electron-transfer step was highly endergonic and the
      calculated outer-sphere rate constant was negligibly small. However, the
      calculated barrier for the inner-sphere electron transfer accompanied by the
      halogen transfer, R-BrI(-) -> RBr-I(-), was nearly 24 kcal mol(-1) lower as
      compared to that calculated for the outer-sphere process and the rate constant of
      such reaction was consistent with the experimental kinetics. A dramatic decrease
      of the electron-transfer barriers (leading to 18-orders of magnitude increase of
      the rate constant) was related to the strong electronic coupling of the donor and
      acceptor within the halogen-bonded precursor complex, as well as to the lower
      solvent reorganization energy and the successor-complex stabilization. 

PMID- 25591990
TI  - The canine isolate Lactobacillus acidophilus LAB20 adheres to intestinal
      epithelium and attenuates LPS-induced IL-8 secretion of enterocytes in vitro.
AB  - BACKGROUND: For a good probiotic candidate, the abilities to adhere to intestinal
      epithelium and to fortify barrier function are considered to be crucial for
      colonization and functionality of the strain. The strain Lactobacillus
      acidophilus LAB20 was isolated from the jejunum of a healthy dog, where it was
      found to be the most pre-dominant lactobacilli. In this study, the adhesion
      ability of LAB20 to intestinal epithelial cell (IECs) lines, IECs isolated from
      canine intestinal biopsies, and to canine, porcine and human intestinal mucus was
      investigated. Further, we studied the ability of LAB20 to fortify the epithelial
      cell monolayer and to reduce LPS-induced interleukin (IL-8) release from
      enterocytes. RESULTS: We found that LAB20 presented higher adhesion to canine
      colonic mucus as compared to mucus isolated from porcine colon. LAB20 showed
      adhesion to HT-29 and Caco-2 cell lines, and importantly also to canine IECs
      isolated from canine intestinal biopsies. In addition, LAB20 increased the
      transepithelial electrical resistance (TER) of enterocyte monolayers and thus
      strengthened the intestinal barrier function. The strain showed also anti
      inflammatory capacity in being able to attenuate the LPS-induced IL-8 production
      of HT-29 cells. CONCLUSION: In conclusion, canine indigenous strain LAB20 is a
      potential probiotic candidate for dogs adhering to the host epithelium and
      showing intestinal barrier fortifying and anti-inflammatory effects.

PMID- 25591993
TI  - Erratum to: Open lung biopsy in nonresolving ARDS frequently identifies diffuse
      alveolar damage regardless of the severity stage and may have implications for
      patient management.

PMID- 25591992
TI  - Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A
      Randomized, Double-Blind, Placebo Controlled Study.
AB  - PURPOSE: We examined the therapeutic effects of avanafil 15 minutes after dosing
      in men with mild to severe erectile dysfunction. MATERIALS AND METHODS: This
      randomized, double-blind, placebo controlled, 12-week study (4-week run-in and 8
      week treatment) randomized 145 men to placebo, 147 to avanafil 100 mg and 148 to
      avanafil 200 mg on demand. The primary efficacy variable was the per subject
      proportion of sexual attempts during the treatment period in which subjects
      achieved erection sufficient for vaginal penetration within approximately 15
      minutes after dosing as measured by a stopwatch. The attempt had to enable
      successful completion of sexual intercourse according to SEP question 3. RESULTS:
      Significantly greater mean per subject percentages of successful intercourse
      attempts within approximately 15 minutes after dosing were observed for avanafil
      100 mg (mean 25.9%, LS mean +/- SE 24.7% +/- 2.9%) and 200 mg (mean 29.1%, LS
      mean 28.2% +/- 2.9%) vs placebo (mean 14.9%, LS mean 13.8% +/- 2.9%, p = 0.001
      and <0.001, respectively). After treatment we noted a statistically significant
      difference between avanafil and placebo in the average per subject proportion of
      successful intercourse attempts according to SEP question 3 as early as 10
      minutes in the 200 mg group and 12 minutes in the 100 mg group. Treatment
      emergent adverse events included headache, upper respiratory tract infection and
      nasal congestion, and most such events were mild or moderate in severity.
      CONCLUSIONS: Avanafil was efficacious within approximately 15 minutes of dosing
      compared to placebo. A statistically significant treatment difference in the
      percentage of successful sexual attempts was demonstrated as early as 10 minutes
      after treatment.

PMID- 25591996
TI  - Inkjet printable luminescent Eu3+-TiO2 doped in sol gel matrix for paper tagging.
AB  - Europium (III) with different concentrations (0.2, 0.4 and 0.8 %)-TiO(2) doped
      silica composite systems were sensitized by sol-gel method. Different
      spectroscopic and microscopic tools characterized the composites. The Europium
      ion incorporated into the liquid silica-titania solution acts as red light
      emission center in the luminescent materials. This luminescent nano composite
      pigment has great potential of application in preparing luminescent ink. Inkjet
      printer loaded with the prepared ink to show its potential usage as tagging
      material performed the printing test on a white paper.

PMID- 25591994
TI  - Conditional overexpression of TGFbeta1 promotes pulmonary inflammation, apoptosis
      and mortality via TGFbetaR2 in the developing mouse lung.
AB  - BACKGROUND: Earlier studies have reported that transforming growth factor beta
      1(TGFbeta1) is a critical mediator of hyperoxia-induced acute lung injury (HALI)
      in developing lungs, leading to impaired alveolarization and a pulmonary
      phenotype of bronchopulmonary dysplasia (BPD). However, the mechanisms
      responsible for the TGFbeta1-induced inflammatory signals that lead to cell death
      and abnormal alveolarization are poorly understood. We hypothesized that TGFbeta1
      signaling via TGFbetaR2 is necessary for the pathogenesis of the BPD pulmonary
      phenotype resulting from HALI. METHODS: We utilized lung epithelial cell-specific
      TGFbeta1 overexpressing transgenic and TGFbetaR2 null mutant mice to evaluate the
      effects on neonatal mortality as well as pulmonary inflammation and apoptosis in
      developing lungs. Lung morphometry was performed to determine the impaired
      alveolarization and multicolor flow cytometry studies were performed to detect
      inflammatory macrophages and monocytes in lungs. Apoptotic cell death was
      measured with TUNEL assay, immunohistochemistry and western blotting and protein
      expression of angiogenic mediators were also analyzed. RESULTS: Our data reveals
      that increased TGFbeta1 expression in newborn mice lungs leads to increased
      mortality, macrophage and immature monocyte infiltration, apoptotic cell death
      specifically in Type II alveolar epithelial cells (AECs), impaired
      alveolarization, and dysregulated angiogenic molecular markers. CONCLUSIONS: Our
      study has demonstrated the potential role of inhibition of TGFbeta1 signaling via
      TGFbetaR2 for improved survival, reduced inflammation and apoptosis that may
      provide insights for the development of potential therapeutic strategies targeted
      against HALI and BPD.

PMID- 25591995
TI  - Differential miRNA expression profiles in the longissimus dorsi muscle between
      intact and castrated male pigs.
AB  - MicroRNAs (miRNAs) are important modulators of skeletal muscle development in
      multiple mammalian species, but their role in skeletal muscle growth in castrated
      male pigs has not been well studied. The aim of the present study was to
      determine the role of miRNAs in longissimus dorsi muscle under castration. Our
      results showed that castration caused a significant decrease in serum
      testosterone levels as well as carcass lean mass, but led to an increase in
      carcass fat mass. Moreover, miRNA expression profiles in skeletal muscle were
      significantly altered by castration, and seven differentially expressed miRNAs
      were discovered. More importantly, functional analysis suggested that these
      differentially expressed miRNAs and their targets are involved in the regulation
      of skeletal muscle contractile function and fat metabolism. Taken together, these
      results demonstrate altered miRNA expression in skeletal muscle of castrated male
      pigs, and suggest a potential mechanism underlying the effects of castration on
      porcine skeletal muscle growth. 

PMID- 25591997
TI  - Photoinduced electron transfer from phenanthrimidazole to magnetic nanoparticles.
AB  - The dynamics of photoinduced electron injection from (E)-1-(4-methoxyphenyl)-2
      styryl-1H-phenanthro [9,10-d]imidazole (MPSPI) synthesised using nano TiO(2) as
      catalyst to Fe(2)O(3) nanocrystal has been studied by FT-IR, absorption,
      fluorescence and lifetime spectroscopic methods. The binding between nanoparticle
      and MPSPI is confirmed by binding constant and binding site. The distance between
      MPSPI and nanoparticle as well as the critical energy transfer distance has been
      obtained. The free energy change (DeltaG(et)) for electron injection has also
      been deduced.

PMID- 25591998
TI  - Microscopy and X-ray spectroscopy analyses for assessment of gilding and
      silvering techniques of Portuguese illuminated manuscripts.
AB  - The objects of this study are various local charters (cartas de foral, in
      Portuguese) granted by Dom Manuel I, King of Portugal (1495-1521), which
      substituted for medieval ones and were intended to achieve an administrative
      unification. These are luxuriously illuminated manuscripts, and our study aims at
      obtaining a better understanding of the gilding and silvering techniques applied
      to the parchments, in which the forais were written, between 1500 and 1520. The
      combined use of microscopy and X-ray spectroscopy analyses allowed us to identify
      the vestigial materials used for making the parchments, including products such
      as salt (NaCl), lime (CaO), pumice stone (SiO2+Al2O3), and chalk (CaCO3). Chalk
      was employed as a whitening agent to give the parchment its final color and
      opacity. Shell-gold and shell-silver mixed in with animal glue or gum binding
      media were directly applied on type 1 and 3 forais, while very thin gold leaves
      (<1 um) were applied over lead-based tempera grounds (50-180 um thick) in type 2
      forais. Silver was always employed in its finest form without a further
      protective layer (thus its recursive state of corrosion), while gold was used in
      various alloy grades. 

PMID- 25591999
TI  - Rapid detection of Gram-negative bacteria and their drug resistance genes from
      positive blood cultures using an automated microarray assay.
AB  - We evaluated the performance of the Verigene Gram-negative blood culture (BC-GN)
      assay (CE-IVD version) for identification of Gram-negative (GN) bacteria and
      detection of resistance genes. A total of 163 GN organisms (72 characterized
      strains and 91 clinical isolates from 86 patients) were tested; among the
      clinical isolates, 86 (94.5%) isolates were included in the BC-GN panel. For
      identification, the agreement was 98.6% (146/148, 95% confidence interval [CI],
      92.1-100) and 70% (7/10, 95% CI, 53.5-100) for monomicrobial and polymicrobial
      cultures, respectively. Of the 48 resistance genes harbored by 43 characterized
      strains, all were correctly detected. Of the 19 clinical isolates harboring
      resistance genes, 1 CTX-M-producing Escherichia coli isolated in polymicrobial
      culture was not detected. Overall, BC-GN assay provides acceptable accuracy for
      rapid identification of Gram-negative bacteria and detection of resistance genes,
      compared with routine laboratory methods despite that it has limitations in the
      number of genus/species and resistance gene included in the panel and it shows
      lower sensitivity in polymicrobial cultures. 

PMID- 25592000
TI  - An overview of various typing methods for clinical epidemiology of the emerging
      pathogen Stenotrophomonas maltophilia.
AB  - Typing of bacterial isolates has been used for decades to study local outbreaks
      as well as in national and international surveillances for monitoring newly
      emerging resistant clones. Despite being recognized as a nosocomial pathogen, the
      precise modes of transmission of Stenotrophomonas maltophilia in health care
      settings are unknown. Due to the high genetic diversity observed among S.
      maltophilia clinical isolates, the typing results might be better interpreted if
      also environmental strains were included. This could help to identify
      preventative measures to be designed and implemented for decreasing the
      possibility of outbreaks and nosocomial infections. In this review, we attempt to
      provide an overview on the most common typing methods used for clinical
      epidemiology of S. maltophilia strains, such as PCR-based fingerprinting
      analyses, pulsed-field gel electrophoresis, multilocus variable number tandem
      repeat analysis, and multilocus sequence type. Application of the proteomic-based
      mass spectrometry by matrix-assisted laser desorption ionization-time of flight
      is also described. Improvements of typing methods already in use have to be
      achieved to facilitate S. maltophilia infection control at any level. In the near
      future, when novel Web-based platforms for rapid data processing and analysis
      will be available, whole genome sequencing technologies will likely become a
      highly powerful tool for outbreak investigations and surveillance studies in
      routine clinical practices. 

PMID- 25592001
TI  - Safety and efficacy of a novel, dry powder fibrin sealant for hemostasis in
      hepatic resection.
AB  - BACKGROUND/AIMS: Fibrocaps is a dry powder fibrin sealant containing human plasma
      derived fibrinogen and thrombin. The safety, efficacy, and application methods
      for Fibrocaps were evaluated in an exploratory, first-in-human, noncomparative,
      clinical study. METHODS: Patients with minor bleeding/oozing after elective
      partial hepatic resection had Fibrocaps applied to the bleeding site either
      directly from the vial or from a spray device, with manual pressure applied using
      a cellulose, collagen, or gelatin sponge, if needed. Safety was evaluated at
      screening and postoperative days 1, 2, and 5, and weeks 4 and 12. The formation
      of anti-thrombin antibodies was assessed at baseline, and after 4 and 12 weeks.
      Time to hemostasis (TTH) within 10 min was determined. RESULTS: Twenty-nine
      patients were treated with Fibrocaps; 6 experienced serious adverse events that
      were not related to the course of treatment. Adverse events occurring in >10% of
      patients were nausea, constipation, hypotension, obstipation, hypokalemia, and
      postoperative pain. Most adverse events were mild or moderate in severity. No
      patient developed anti-thrombin antibodies. The percentage of patients who
      achieved hemostasis was 93%; the median TTH was 3.8 min (range 0.3-10.3). Manual
      pressure was applied with Fibrocaps in 19 patients and considered beneficial in
      most. CONCLUSION: Fibrocaps was well tolerated in patients undergoing elective
      hepatic resection and resulted in rapid hemostasis. These safety and efficacy
      results support further clinical testing of this ready-to-use fibrin sealant as
      an adjunct to surgical hemostasis.

PMID- 25592003
TI  - Comparison of the efficacy of olopatadine and fexofenadine in chronic idiopathic
      urticaria patients: a crossover study.
AB  - Olopatadine is one of the second-generation H1 antihistamines that were used for
      treating allergic disorders initially in Asia, and now also in Western countries.
      Whereas several trials compared the efficacy on chronic urticaria among second
      generation H1 antihistamines, no study has directly compared the clinical
      efficacy between olopatadine and other H1 antihistamines in patients with chronic
      idiopathic urticaria (CIU). In this study, we address this issue for the first
      time and conclude that olopatadine is a good candidate for the treatment of CIU.

PMID- 25592002
TI  - Dietary patterns and colorectal cancer: results from a Canadian population-based
      study.
AB  - BACKGROUND: The relationship between major dietary patterns and colorectal cancer
      (CRC) in other populations largely remains consistent across studies. The
      objective of the present study is to assess if dietary patterns are associated
      with the risk of CRC in the population of Newfoundland and Labrador (NL).
      METHODS: Data from a population based case-control study in the province of NL
      were analyzed, including 506 CRC patients (306 men and 200 women) and 673
      controls (400 men and 273 women), aged 20-74 years. Dietary habits were assessed
      by a 169-item food frequency questionnaire (FFQ). Logistic regression analyses
      were performed to investigate the association between dietary patterns and the
      CRC risk. RESULTS: Three major dietary patterns were derived using factor
      analysis, namely a Meat-diet pattern, a Plant-based diet pattern and a Sugary
      diet pattern. In combination the three dietary patterns explained 74% of the
      total variance in food intake. Results suggest that the Meat-diet and the Sugary
      diet increased the risk of CRC with corresponding odds ratios (ORs) of 1.84 (95%
      CI: 1.19-2.86) and 2.26 (95% CI: 1.39-3.66) for people in the highest intake
      quintile compared to those in the lowest. Whereas plant-based diet pattern
      decreases the risk of CRC with a corresponding OR of 0.55 (95% CI: 0.35-0.87).
      Even though odds ratios (ORs) were not always statistically significant, largely
      similar associations across three cancer sites were found: the proximal colon,
      the distal colon, and the rectum. CONCLUSION: The finding that Meat-diet/Sugary
      diet patterns increased and Plant-based diet pattern decreased the risk of CRC
      would guide the promotion of healthy eating for primary prevention of CRC in this
      population.

PMID- 25592004
TI  - Inadequate supply of vitamins and DHA in the elderly: implications for brain
      aging and Alzheimer-type dementia.
AB  - Alzheimer's disease (AD) is the most prevalent, severe, and disabling cause of
      dementia worldwide. To date, AD therapy is primarily targeted toward palliative
      treatment of symptoms rather than prevention of disease progression. So far, no
      pharmacologic interventions have changed the onset or progression of AD and their
      use is accompanied by side effects. The major obstacle in managing AD and
      designing therapeutic strategies is the difficulty in retarding neuronal loss in
      the diseased brain once the pathologic events leading to neuronal death have
      started. Therefore, a promising alternative strategy is to maintain a healthy
      neuronal population in the aging brain for as long as possible. One factor
      evidently important for neuronal health and function is the optimal supply of
      nutrients necessary for maintaining normal functioning of the brain. Mechanistic
      studies, epidemiologic analyses, and randomized controlled intervention trials
      provide insight to the positive effects of docosahexaenoic acid (DHA) and
      micronutrients such as the vitamin B family, and vitamins E, C, and D, in helping
      neurons to cope with aging. These nutrients are inexpensive in use, have
      virtually no side effects when used at recommended doses, are essential for life,
      have established modes of action, and are broadly accepted by the general public.
      This review provides some evidence that the use of vitamins and DHA for the aging
      population in general, and for individuals at risk in particular, is a viable
      alternative approach to delaying brain aging and for protecting against the onset
      of AD pathology. 

PMID- 25592005
TI  - Nutritional factors in the prevention and management of coronary artery disease
      and heart failure.
AB  - Nutritional factors such as magnesium, folic acid, vitamins B12 and B6, L
      arginine, and polyunsaturated fatty acids (PUFAs) appear to be significantly
      beneficial for patients with coronary artery disease (CAD), and in the prevention
      and arresting the progression of HF and cardiac arrhythmias. Additionally,
      ingestion of adequate amounts of protein and maintaining normal concentrations of
      plasma albumin seem to be essential for these patients. These nutrients closely
      interact with the metabolism of L-arginine-nitric oxide (NO) system, essential
      fatty acids, and eicosanoids such that beneficial products such as NO,
      prostaglandin E1, prostacyclin, prostaglandin I3, lipoxins, resolvins, and
      protectins are generated and synthesis of proinflammatory cytokines is suppressed
      that results in platelet anti-aggregation, vasodilation, angiogenesis, and
      prevention of CAD, cardiac arrhythmias, and stabilization of HF. This implies
      that individuals at high risk for CAD, cardiac arrhythmias, and HF and those who
      have these diseases need to be screened for plasma levels of magnesium, folic
      acid, vitamins B12 and B6, L-arginine, NO, various PUFAs, lipoxin A4, resolvins,
      protectins, asymmetrical dimethylarginine (an endogenous inhibitor of NO),
      albumin, and various eicosanoids and cytokines and correct their abnormalities to
      restore normal physiology.

PMID- 25592006
TI  - Effect of post-exercise caffeine and green coffee bean extract consumption on
      blood glucose and insulin concentrations.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of ingesting
      caffeine and green coffee bean extract on blood glucose and insulin
      concentrations during a post-exercise oral glucose tolerance test. METHODS: Ten
      male cyclists (age: 26 +/- 5 y; height: 179.9 +/- 5.4 cm; weight: 77.6 +/- 13.3
      kg; body mass index: 24 +/- 4.3 kg/m(2); VO2 peak: 55.9 +/- 8.4 mL.kg.min(-1))
      participated in this study. In a randomized order, each participant completed
      three 30-min bouts of cycling at 60% of peak power output. Immediately after
      exercise, each participant consumed 75 g of dextrose with either 5 mg/kg body
      weight of caffeine, 10 mg/kg of green coffee bean extract (5 mg/kg chlorogenic
      acid), or placebo. Venous blood samples were collected immediately before and
      after exercise during completion of the oral glucose tolerance test. RESULTS: No
      significant time * treatment effects for blood glucose and insulin were found.
      Two-h glucose and insulin area under the curve values, respectively, for the
      caffeine (658 +/- 74 mmol/L and 30,005 +/- 13,304 pmol/L), green coffee bean
      extract (637 +/- 100 mmol/L and 31,965 +/- 23,586 pmol/L), and placebo (661 +/-
      77 mmol/L and 27,020 +/- 12,339 pmol/L) trials were not significantly different
      (P > 0.05). CONCLUSION: Caffeine and green coffee bean extract did not
      significantly alter postexercise blood glucose and insulin concentrations when
      compared with a placebo. More human research is needed to determine the impact of
      these combined nutritional treatments and exercise on changes in blood glucose
      and insulin.

PMID- 25592008
TI  - Iron metabolism in infants: influence of bovine lactoferrin from iron-fortified
      formula.
AB  - OBJECTIVE: The aim of this study was to evaluate whether an iron-fortified
      formula with a concentration of lactoferrin would significantly improve the
      hematologic indexes and iron status in term infants compared with those same
      values in infants fed an iron-fortified formula without lactoferrin. METHOD: In
      this prospective, multicenter, controlled intervention study, 260 infants ages 4
      to 6 mo were selected from six maternal and children's health care hospitals in
      the area. All infants were divided into two groups with the sequence of
      outpatient: lactoferrin-fortified formula milk group (fortified group, FG,
      containing lactoferrin 38 mg/100 g milk and iron element 4 mg/100 g milk) and no
      lactoferrin fortified milk (control group, CG, containing lactoferrin 0 mg/100 g
      milk and iron element 4 mg/100 g milk) for 3 mo. The levels of weight, height,
      and head circumference and the concentration of hemoglobin (Hb), serum ferritin
      (SF), and serum transferring receptor (sTfR) were measured and sTfR-SF index (TFR
      F index), total body iron content (TBIC) and low height for age (HAZ), low weight
      for age (WAZ), and low weight for height (WHZ) were computed before and after the
      intervention, respectively. RESULTS: In all, 213 (115 in FG and 98 in CG) infants
      completed the intervention trial and all measurements of biochemical indicators.
      There were no significant differences in the average amount of daily intake of
      formula milk (94.3 +/- 9.8 g versus 88.2 +/- 8.7 g for FG and CG; P > 0.05) and
      iron element (3.8 +/- 0.4 mg versus 3.7 +/- 0.6 mg for FG and CG; P > 0.05). The
      average amount of daily intake of lactoferrin for infants in FG group was 35.8 +/
      3.7 mg. The levels of weight, WAZ, WHZ, Hb, SF, TFR-F index, and TBIC after
      intervention of infants in FG were all significantly higher than those of infants
      in CG weight, 8723 +/- 245 g versus 8558 +/- 214g; WAZ, 1.02 +/- 0.31 versus 0.44
      +/- 0.18; WHZ, 0.98 +/- 0.31 versus 0.41 +/- 0.12; Hb, 125.5 +/- 15.4 g/L versus
      116.9 +/- 13.1 g/L; SF, 44.7 +/- 17.2 MUg/L versus 31.6 +/- 18.4 MUg/L; TFR-F
      index, 1.88 +/- 0.41 versus 1.26 +/- 0.39; TBIC, 6.12 +/- 0.78 mg/kg versus 5.26
      +/- 0.55 mg/kg for FG and CG; P < 0.05), but significantly lower (P < 0.05) for
      the prevalence of anemia (4.1% versus 7.5%), iron deficiency (13.9% versus
      24.4%), and iron-deficient anemia (1.7% versus 6.1%). CONCLUSION: When infants
      who were exclusively breastfed were supplemented with lactoferrin-fortified milk,
      significant increases in TBIC and iron absorption in the intestine were seen.

PMID- 25592007
TI  - High dietary acid load is associated with increased prevalence of hypertension:
      the Furukawa Nutrition and Health Study.
AB  - OBJECTIVE: Acid-base status has been suggested to influence blood pressure, but
      there is a paucity of epidemiologic evidence linking dietary acid load to
      hypertension. We examined cross-sectionally the association between dietary acid
      load and hypertension in a Japanese working population. METHODS: Data were
      derived from health surveys from 2028 employees, ages 18 to 70 y, in two
      workplaces in Japan. A validated brief diet history questionnaire was used to
      assess diet. Two measures were used to characterize dietary acid load: potential
      renal acid load and estimated net endogenous acid production, which were derived
      from nutrient intakes. Multilevel logistic regression was used to examine the
      association between dietary acid load and hypertension with adjustment of
      potential confounding variables. RESULTS: High dietary acid load was suggestively
      associated with increased prevalence of hypertension. The multivariable adjusted
      odds ratios (95% confidence interval) of hypertension for the lowest through
      highest tertiles of net endogenous acid production were 1.00 (reference), 1.07
      (0.80-1.42), and 1.33 (0.998-1.78), respectively (P for trend = 0.053). This
      positive association was statistically significant among normal-weight (body mass
      index <23 kg/m(2); P for trend = 0.03) and non-shift workers (P for trend =
      0.04). Similar positive associations were observed between potential renal acid
      load and hypertension. CONCLUSIONS: The present findings suggest that high
      dietary acid load may be associated with increased prevalence of hypertension
      among those who were normal weight and non-shift workers.

PMID- 25592009
TI  - Eating behavior in Portuguese higher education students: the effect of social
      desirability.
AB  - OBJECTIVES: The aim of this study was to relate social desirability with eating
      behavior dimensions among higher education students in Portugal, and to assess
      the effect of social desirability on the association between pairs of eating
      behavior dimensions. METHODS: Data from 266 higher education students (62.8%
      women) aged between 18 and 27 y were evaluated. Social desirability and several
      eating behavior dimensions (emotional and external eating, flexible and rigid
      restraint, binge eating, and eating self-efficacy) were assessed. RESULTS: In
      both women and men, social desirability showed negative associations with
      emotional, external, and binge eating, and positive associations with eating self
      efficacy. For the majority of the correlations, the control for social
      desirability led to a decrease in the strength of the association: Social
      desirability showed a greater effect on the associations between external and
      binge eating, external eating and eating self-efficacy, binge eating and eating
      self-efficacy, and emotional and external eating. CONCLUSION: This study
      demonstrated that social desirability should be considered when assessing the
      dimensions of eating behavior, namely eating self-efficacy and dimensions related
      to overeating.

PMID- 25592010
TI  - Differential effects of repetitive oral administration of monosodium glutamate on
      interstitial glutamate concentration and muscle pain sensitivity.
AB  - OBJECTIVE: The aim of this study was to determine the relationship of high daily
      monosodium glutamate (MSG) consumption with glutamate concentrations in jaw
      muscle, saliva, and serum, and muscle pain sensitivity in healthy participants.
      METHODS: A randomized, double-blinded, placebo-controlled study was conducted to
      investigate the effect of repetitive consumption of high-dose MSG on glutamate
      concentration in the masseter muscles measured by microdialysis and muscle pain
      sensitivity. In five contiguous experimental daily sessions, 32 healthy
      participants drank MSG (150 mg/kg) or NaCl (24 mg/kg) diluted with a 400 mL soda.
      The concentrations of glutamate before and after the ingestion were assessed in
      dialysate and plasma samples on the first and last days. Saliva glutamate
      concentration was assessed every day. Pressure pain threshold, pressure pain
      tolerance, autonomic parameters (heart rate, systolic and diastolic blood
      pressures) and reported side effects also were assessed. RESULTS: No significant
      change was noted in the baseline concentration of glutamate in the masseter
      muscle, blood, or saliva, but the peak concentration in the masseter muscle
      increased significantly between day 1 and 5. A statistically significant increase
      in systolic and diastolic blood pressures after MSG administration was observed,
      as well as a significantly higher frequency of reports of nausea and headache in
      the MSG group. No robust effect of MSG on muscle sensitivity was found.
      CONCLUSION: Interstitial glutamate concentration in the masseter muscle is not
      highly disturbed by excessive repetitive intake of MSG in healthy man.

PMID- 25592012
TI  - Effects of polymorphisms in endothelial nitric oxide synthase and folate
      metabolizing genes on the concentration of serum nitrate, folate, and plasma
      total homocysteine after folic acid supplementation: a double-blind crossover
      study.
AB  - OBJECTIVES: A number of studies have explored the effects of dietary nitrate on
      human health. Nitrate in the blood can be recycled to nitric oxide, which is an
      essential mediator involved in many important biochemical mechanisms. Nitric
      oxide is also formed in the body from l-arginine by nitric oxide synthase. The
      aim of this study was to investigate whether genetic polymorphisms in endothelial
      nitric oxide synthase (eNOS) and genes involved in folate metabolism affect the
      concentration of serum nitrate, serum folate, and plasma total homocysteine in
      healthy individuals after folic acid supplementation. METHODS: In a randomized
      double-blind, crossover study, participants were given either folic acid 800
      MUg/d (n = 52) or placebo (n = 51) for 2 wk. Wash-out period was 2 wk. Fasting
      blood samples were collected, DNA was extracted by salting-out method and the
      polymorphisms in eNOS synthase and folate genes were genotyped by polymerase
      chain reaction methods. Measurement of serum nitrate and plasma total
      homocysteine (p-tHcy) concentration was done by high-performance liquid
      chromatography. RESULTS: The concentration of serum nitrate did not change in
      individuals after folic acid supplements (trial 1); however, the concentration of
      serum nitrate increased in the same individuals after placebo (P = 0.01) (trial
      2). The individuals with three polymorphisms in eNOS gene had increased
      concentration of serum folate and decreased concentration of p-tHcy after folic
      acid supplementation. Among the seven polymorphisms tested in folate metabolizing
      genes, serum nitrate concentration was significantly decreased only in DHFR del
      19 gene variant. A significant difference in the concentration of serum nitrate
      was detected among individuals with MTHFR C > T677 polymorphisms. CONCLUSIONS:
      Polymorphisms in eNOS and folate genes affect the concentration of serum folate
      and p-tHcy but do not have any effect on the concentration of NO3 in healthy
      individuals after folic acid supplementation.

PMID- 25592011
TI  - Plasma micronutrient levels and telomere length in children.
AB  - OBJECTIVE: Telomeres are long hexamer (TTAGGG) repeats at the ends of
      chromosomes, and contribute to maintenance of chromosomal stability. Telomere
      shortening has been linked to cancers and other chronic diseases in adults,
      although evidence for causal associations is limited. The aim of this study was
      to determine whether nutritional factors are associated with telomere length (TL)
      in children. METHODS: We conducted a cross-sectional study of nutritional factors
      and TL in 437 children between 2009 and 2011. Healthy children ages 3, 6, and 9 y
      provided blood samples, and their parents completed a food frequency
      questionnaire and a telephone interview about relevant environmental exposures.
      TL and blood micronutrient levels were measured, and genotyping at 10 loci was
      undertaken. Associations between the micronutrients and other variables were
      assessed using linear regression. RESULTS: No significant main or interactive
      effects of age or sex were seen. After adjustment for age, sex, parental
      education, and month of blood collection, TL was inversely associated with plasma
      zinc, and shorter in children with the homozygous mutant genotype of the RFC G80A
      (rs1051266) polymorphism. CONCLUSIONS: To the best of our knowledge, this is the
      first investigation of the association between telomere length and micronutrients
      in healthy children. The reason for the inverse relationship of TL with zinc is
      unknown but could be the result of an increase in telomere sequence deletions
      caused by labile zinc induction of oxidative stress. These findings should be
      corroborated in other studies before nutritional recommendations might be
      considered.

PMID- 25592013
TI  - Greek adolescents and the Mediterranean diet: factors affecting quality and
      adherence.
AB  - OBJECTIVE: Evaluation of adolescents' adherence to the Mediterranean diet (AMD)
      and the connection to anthropometric, demographic, socioeconomic, and lifestyle
      characteristics. METHODS: In all, 525 adolescents aged 12 to 18 y from Athens and
      Heraklion, Greece, participated in this cross-sectional, school-based study,
      which took place during March and April 2012. The dependent variable was scored
      on the KIDMED test, with score >8 indicating an optimal Mediterranean diet (MD).
      Analysis included chi(2) test and Student's t test for the association between
      variables. Linear regression analysis was used to identify the determinants of
      AMD. A two-sided P-value < 0.05 was considered statistically significant.
      RESULTS: Of the participants, 21% had very good AMD. Positive predictors were
      mother's educational level (P < 0.01), living with both parents (P < 0.05), and
      residing in a smaller city (P < 0.01). Negative predictors were age (P < 0.05),
      >4-h computer use per day (P < 0.01), and lack of physical activity (P < 0.01).
      No correlation was found between AMD and body mass index (P > 0.05). CONCLUSIONS:
      Several anthropometric, demographic, socioeconomic, and lifestyle characteristics
      were significantly associated with AMD. It is highly important that children and
      adolescents adhere at a very young age to the MD as the healthier dietary choice.
      Further researchers might explore whether the economic recession in Greece has
      any effects on adolescents' dietary habits.

PMID- 25592014
TI  - Comparative effectiveness of plant-based diets for weight loss: a randomized
      controlled trial of five different diets.
AB  - OBJECTIVE: The aim of this study was to determine the effect of plant-based diets
      on weight loss. METHODS: Participants were enrolled in a 6-mo, five-arm,
      randomized controlled trial in 2013 in South Carolina. Participants attended
      weekly group meetings, with the exception of the omnivorous group, which served
      as the control and attended monthly meetings augmented with weekly e-mail
      lessons. All groups attended monthly meetings for the last 4 mo of the study.
      Diets did not emphasize caloric restriction. RESULTS: Overweight adults (body
      mass index 25-49.9 kg/m(2); age 18-65 y, 19% non-white, and 27% men) were
      randomized to a low-fat, low-glycemic index diet: vegan (n = 12), vegetarian (n =
      13), pesco-vegetarian (n = 13), semi-vegetarian (n = 13), or omnivorous (n = 12).
      Fifty (79%) participants completed the study. In intention-to-treat analysis, the
      linear trend for weight loss across the five groups was significant at both 2 (P
      < 0.01) and 6 mo (P < 0.01). At 6 mo, the weight loss in the vegan group (-7.5%
      +/- 4.5%) was significantly different from the omnivorous (-3.1% +/- 3.6%; P =
      0.03), semi-vegetarian (-3.2% +/- 3.8%; P = 0.03), and pesco-vegetarian (-3.2% +/
      3.4%; P = 0.03) groups. Vegan participants decreased their fat and saturated fat
      more than the pesco-vegetarian, semi-vegetarian, and omnivorous groups at both 2
      and 6 mo (P < 0.05). CONCLUSIONS: Vegan diets may result in greater weight loss
      than more modest recommendations.

PMID- 25592015
TI  - Selenium reduces bradykinesia and DNA damage in a rat model of Parkinson's
      disease.
AB  - OBJECTIVE: The aim of this study was to explore the effects of selenium (Se) on
      locomotor activity and DNA damage in a rat model of Parkinson's disease (PD)
      induced by paraquat (PQ). METHODS: Forty-eight male Wistar rats were divided into
      four groups: control group (n = 12), Se group (n = 12), PQ group (n = 12), and Se
      + PQ group (n = 12). PQ was administered intraperitoneally (10 mg/kg). Se was
      offered in the drinking water at a concentration of 11.18 MUg/L. Locomotor
      activity was evaluated weekly using the narrow beam test. The comet assay was
      performed to assess the level of DNA damage in leukocytes and in brain cells.
      RESULTS: As expected, increased DNA damage was found in the PQ group compared
      with the control and Se groups (P < 0.001). Interestingly, coadministration of Se
      and PQ effectively prevented the harmful effects of the toxin in locomotor
      activity and at the molecular level, reducing bradykinesia (P < 0.01) and DNA
      damage in leukocytes compared with the PQ-only group (P < 0.001), whereas the
      levels of DNA damage were comparable to those found in the control and Se groups
      (P > 0.05). Using the comet assay to analyze brain cells, no differences were
      found between the groups with regard to damage index (P = 0.774), damage
      frequency (P = 0.817), or non-detectable cell nuclei (P = 0.481). CONCLUSION: In
      this experimental model of PQ-induced PD, the use of Se could contribute to the
      maintenance of locomotor activity and the integrity of leukocytes DNA. No changes
      in the levels of DNA damage in brain cells were observed between the experimental
      groups.

PMID- 25592016
TI  - Induction of histone H3K4 methylation at the promoter, enhancer, and transcribed
      regions of the Si and Sglt1 genes in rat jejunum in response to a high-starch/low
      fat diet.
AB  - OBJECTIVE: Histone methylation patterns are associated with various aspects of
      biology, including transcriptional regulation. Methylation of histone H3 at
      lysine 4 (H3K4) leads to transcriptional activation through recruitment of
      transcription activation complexes onto target genes; in contrast, methylation of
      histone H3K9, or histone H4K20, leads to transcriptional inactivation attracting
      heterochromatin protein 1 (HP1). It is not yet known whether jejunal induction of
      sucrase-isomaltase (Si) and sodium-dependent glucose cotransporter (Sglt1) genes
      by intake of a high-starch/low-fat diet in rats is regulated by coordinated
      changes of these histone methylation events. In the present study, we
      investigated whether these histone modifications at the promoter, enhancer, and
      transcribed regions of Si and Sglt1 genes in rat jejunum are affected by
      consumption of a high-starch/low-fat diet. METHODS: Chromatin immunoprecipitation
      assays using antibodies against methylated-histone H3K4, H3K9, H4K20, and HP1
      were performed at various regions associated with the Si and Sglt1 genes in
      jejunum of rats fed a high-starch/low-fat diet or a low-starch/high-fat diet for
      7 d. RESULTS: Feeding rats the high-starch/low-fat diet induced mono-, di-, and
      trimethylation of histone H3K4 on the promoter and transcribed regions of the Si
      and Sglt1 genes. In contrast, methylation of histones H3K9 and H4K20, and binding
      of HP1 at these gene regions, were not affected by the high-starch/low-fat diet.
      CONCLUSION: These observations suggest that induction of Si and Sglt1 gene
      expression in rat jejunum by a high-starch/low-fat diet intake is positively
      associated with histone H3K4 methylation, but not with histone H3K9/H4K20
      methylation, or with binding of HP1.

PMID- 25592017
TI  - Ascorbic acid deficiency increases endotoxin influx to portal blood and liver
      inflammatory gene expressions in ODS rats.
AB  - OBJECTIVE: The aim of this study was to determine whether ascorbic acid (AsA)
      deficiency-induced endotoxin influx into portal blood from the gastrointestinal
      tract contributes to the inflammatory changes in the liver. METHOD: The
      mechanisms by which AsA deficiency provokes inflammatory changes in the liver
      were investigated in Osteogenic Disorder Shionogi (ODS) rats (which are unable to
      synthesize AsA). Male ODS rats (6-wk-old) were fed a diet containing sufficient
      (300 mg/kg) AsA (control group) or a diet without AsA (AsA-deficient group) for
      14 or 18 d. RESULTS: On day 14, the hepatic mRNA levels of acute-phase proteins
      and inflammation-related genes were significantly higher in the AsA-deficient
      group than the control group, and these elevations by AsA deficiency were
      exacerbated on day 18. The serum concentrations of interleukin (IL)-1beta and IL
      6, which induce acute-phase proteins in the liver, were also significantly
      elevated on day 14 in the AsA-deficient group compared with the respective values
      in the control group. IL-1beta mRNA levels in the liver, spleen, and lung were
      increased by AsA deficiency. Moreover, on both days 14 and 18, the portal blood
      endotoxin concentration was significantly higher in the AsA-deficient group than
      in the control group, and a significant correlation between serum IL-1beta
      concentrations and portal endotoxin concentrations was found in AsA-deficient
      rats. In the histologic analysis of the ileum tissues, the number of goblet cells
      per villi was increased by AsA deficiency. CONCLUSION: These results suggest that
      AsA deficiency-induced endotoxin influx into portal blood from the
      gastrointestinal tract contributes to the inflammatory changes in the liver.

PMID- 25592018
TI  - Chemical composition and immunomodulatory effects of enzymatic protein
      hydrolysates from common carp (Cyprinus carpio) egg.
AB  - OBJECTIVES: The aim of this study was to prepare protein hydrolysates from
      underutilized common carp (Cyprinus carpio) egg and to investigate their
      immunomodulatory effects in vivo. METHODS: Common carp (Cyprinus carpio) egg
      (roe) was hydrolysed by pepsin, trypsin, and Alcalase. Chemical composition
      (proximate, amino acid, mineral and fatty acid compositions) and molecular mass
      distribution of the three hydrolysates were determined. The carp egg protein
      hydrolysates (CEPHs) were evaluated for their immunomodulatory effects in BALB/c
      mice. CEPHs (0.25, 0.5 and 1 g/kg body weight) were orally administered daily to
      female BALB/c mice (4-6 wk, 18-20 g) for a period of 45 d. After 45 d, mice were
      sacrificed and different tissues were collected for the immunologic
      investigations. RESULTS: The three hydrolysates contained high protein content
      (64%-73%) with all essential amino acids, and good proportion of omega-3 fatty
      acids, especially docosahexaenoic acid. Molecular mass analysis of hydrolysates
      confirmed the conversion of large-molecular-weight roe proteins into peptides of
      different sizes (5-90 kDa). The three hydrolysates significantly enhanced the
      proliferation of spleen lymphocytes. Pepsin hydrolysate (0.5 g/kg body weight)
      significantly increased the splenic natural killer cell cytotoxicity, mucosal
      immunity (secretory immunoglobulin A) in the gut and level of serum
      immunoglobulin A. Whereas Alcalase hydrolysate induced significant increases in
      the percentages of CD4+ and CD8+ cells in spleen. CONCLUSIONS: The results
      demonstrate that CEPHs are able to improve the immune system and further reveal
      that different CEPHs may exert differential influences on the immune function.
      These results indicate that CEPHs could be useful for several applications in the
      health food, pharmaceutical, and nutraceutical industries.

PMID- 25592019
TI  - Milk basic protein supplementation enhances fracture healing in mice.
AB  - OBJECTIVES: There is an unmet need for agents that can stimulate bone healing.
      The goal of this study was to evaluate the effects of basic proteins from milk
      whey (milk basic protein [MBP]) on fracture healing in mice. METHODS: Closed
      tibial transverse fractures were generated in 6-wk-old male C3 H/HeJ mice given
      either tap water or MBP-supplemented water for 3, 7, 14, 28, and 56 d after
      fracture generation. The tibial tissues were analyzed by radiography, MUCT, and a
      three-point bending test. The expression levels of genes associated with bone
      metabolism were analyzed by real-time reverse transcription-polymerase chain
      reaction. RESULTS: Quantitative MUCT analysis showed that MBP-treated fractured
      tibiae had a larger hard callus in the sectional area and a larger volume
      compared with fractured tibiae without MBP treatment. The expression levels of
      genes associated with chondrogenesis and osteogenesis showed greater increases in
      fractured tibiae with MBP treatment. Significant increases in the callus
      mechanical properties were found in MBP-treated tibiae. CONCLUSIONS: MBP
      supplementation has the potential to improve fracture healing and bone strength
      in mouse tibiae. MBP could be a potential safe, low-cost, and easily administered
      nutritional element to prevent secondary fractures in patients with bone
      fractures.

PMID- 25592020
TI  - Lymphocyte vitamin C levels as potential biomarker for progression of Parkinson's
      disease.
AB  - OBJECTIVES: Vitamin C is a major antioxidant and also is known as a
      neuromodulator in dopaminergic neurons. The aim of this study was to investigate
      the association between lymphocyte and plasma vitamin C levels in various stages
      of Parkinson's disease (PD). METHODS: Sixty-two individuals with PD (age 71 +/-
      8.8 y [mean +/- SD]) being treated at Shizuoka General Hospital from December
      2007 to August 2013 were consecutively recruited. PD severity was classified
      using the Hoehn-Yahr scale for staging PD. Fasting blood samples were collected,
      and plasma and lymphocyte vitamin C levels were measured. The association between
      PD severity and vitamin C levels was estimated by ordinal logistic regression
      with confounding variables. RESULTS: The distribution of Hoehn-Yahr stages in
      patients was as follows: stage I, 7; II, 28; III, 16; and IV, 11. Lymphocyte
      vitamin C levels in patients with severe PD were significantly lower (odds ratio
      [OR], 0.87; 95% confidence interval [CI], 0.80-0.97; P < 0.01) compared with
      those at less severe stages. Plasma vitamin C levels also tended to be lower in
      patients with severe PD; however, this was not significant (OR, 0.98; 95% CI,
      0.96-1.00; P = 0.09). CONCLUSIONS: Our findings suggest that lymphocyte vitamin C
      levels in the peripheral blood may be a potentially useful biomarker for the
      progression of PD.

PMID- 25592021
TI  - Omega-3 fatty acids for the treatment of hypertriglyceridemia during the second
      trimester.
AB  - OBJECTIVE: Serum triacylglycerol (TG) levels increase during pregnancy. High
      serum TG levels may elicit acute pancreatitis; therefore, it is important that
      pregnant women are managed well to abrogate the rapid rise of TG levels in
      pregnancy. The aim of this study was to report on the effect of eicosapentaenoic
      acid administration on pregnant women with hypertriacylglycerolemia in the second
      trimester. METHOD: We report on four patients who presented to Kumamoto
      University Hospital from January 2005 to March 2013. FINDINGS: All four patients
      delivered neonates at term without complicating acute pancreatitis. Additionally,
      in three cases of multipara, the maximum serum TG levels were decreased to 10% to
      49% of their preceding pregnancy. CONCLUSION: Oral eicosapentaenoic acid
      administration might be a safe and useful treatment for hypertriacylglycerolemia
      during pregnancy and may prevent the development of acute pancreatitis.

PMID- 25592022
TI  - Hypoglycemia in hospitalized patients receiving parenteral nutrition.

PMID- 25592023
TI  - Author's response re. "Review on emu products for use as complementary and
      alternative medicine".

PMID- 25592024
TI  - Re. "Bioelectrical impedance vector analysis, phase-angle assessment and
      relationship with malnutrition risk in a cohort of frail older hospital patients
      in the United Kingdom".

PMID- 25592025
TI  - Re. "Fructose content in popular beverages made with and without high fructose
      corn syrup".

PMID- 25592026
TI  - Computer-aided nodule detection system: results in an unselected series of
      consecutive chest radiographs.
AB  - RATIONALE AND OBJECTIVES: To evaluate the performance of a computer-aided
      detection (CAD) system with bone suppression imaging when applied to unselected
      consecutive chest radiographs (CXRs) with computed tomography (CT) correlation.
      MATERIALS AND METHODS: This study included 586 consecutive patients with standard
      or portable CXRs who had a chest CT scan on the same day. Among the 586 CXRs, 438
      had various abnormalities, including 46 CXRs with 66 lung nodules, and 148 CXRs
      had no significant abnormalities. A commercially available CAD system was applied
      to all 586 CXRs. True nodules and false positives (FPs) marked on CXRs by the CAD
      system were evaluated based on the corresponding chest CT findings. RESULTS: The
      CAD system marked 47 of 66 (71%) lung nodules in this consecutive series of CXRs.
      The mean FP rate per image was 1.3 across all 586 CXRs, with 1.5 FPs per image on
      the 438 abnormal CXRs and 0.8 FPs per image on the 148 normal CXRs. A total of
      41% of the 752 FP marks were related to non-nodule pathologic findings.
      CONCLUSIONS: A currently available CAD system marked 71% of radiologist
      identified lung nodules in a large consecutive series of CXRs, and 41% of "false"
      marks were caused by pathologic findings.

PMID- 25592027
TI  - "Flipping" the introductory clerkship in radiology: impact on medical student
      performance and perceptions.
AB  - RATIONALE AND OBJECTIVES: Among methods of "blended learning" (ie, combining
      online modules with in-class instruction), the "flipped classroom" involves
      student preclass review of material while reserving class time for interactive
      knowledge application. We integrated blended learning methodology in a "flipped"
      introductory clerkship in radiology, and assessed the impact of this approach on
      the student educational experience (performance and perception). MATERIALS AND
      METHODS: In preparation for the "flipped clerkship," radiology faculty and
      residents created e-learning modules that were uploaded to an open-source
      website. The clerkship's 101 rising third-year medical students were exposed to
      different teaching methods during the course, such as blended learning,
      traditional lecture learning, and independent learning. Students completed
      precourse and postcourse knowledge assessments and surveys. RESULTS: Student
      knowledge improved overall as a result of taking the course. Blended learning
      achieved greater pretest to post-test improvement of high statistical
      significance (P value, .0060) compared to lecture learning alone. Blended
      learning also achieved greater pretest to post-test improvement of borderline
      statistical significance (P value, .0855) in comparison to independent learning
      alone. The difference in effectiveness of independent learning versus lecture
      learning was not statistically significant (P value, .2730). Student perceptions
      of the online modules used in blended learning portions of the course were very
      positive. They specifically enjoyed the self-paced interactivity and the ability
      to return to the modules in the future. CONCLUSIONS: Blended learning can be
      successfully applied to the introductory clerkship in radiology. This teaching
      method offers educators an innovative and efficient approach to medical student
      education in radiology.

PMID- 25592028
TI  - Arthrodesis of the carpometacarpal joint of the thumb with plate fixation and
      bone grafting: a retrospective review.
AB  - BACKGROUND: Arthrodesis of the carpometacarpal (CM) joint of the thumb has been
      recognized as a common technique that gives pain relief, stability, and strength,
      but it has some disadvantages, such as nonunion, pantrapezial osteoarthritis, and
      reduced mobility. METHODS: Thirteen thumbs of 12 patients with CM joint arthritis
      who underwent CM joint arthrodesis were reviewed retrospectively. The average age
      of the patients was 61.0 years. The follow-up period ranged from 2 to 5 years.
      Arthrodesis was performed with a T-plate and an autogenous iliac cancellous bone
      graft for all patients. RESULTS: All thumbs had radiographic evidence of union,
      and there was no nonunion. No reduction of motion of the interphalangeal and
      metacarpophalangeal joint of the thumb was found after surgery. Postoperatively,
      scaphotrapeziotrapezoid arthritis and metacarpophalangeal arthritis progressed in
      two joints each. The Disabilities of the Arm, Shoulder, and Hand score improved
      from 39.9 (range 8-69) to 11.1 (range 0-23.1). All patients had no or slight
      problems of the thumb and no complaints related to the pelvis in daily living and
      were either very satisfied or satisfied with the surgery. CONCLUSIONS:
      Arthrodesis of the thumb CM joint with a plate and bone graft achieved
      satisfactory results in all cases with very few complications. This procedure is
      a valuable tool in middle-aged and elderly patients with thumb CM joint
      arthritis.

PMID- 25592029
TI  - Simultaneous evaluation of articular cartilage and subchondral bone from
      immobilized knee in rats by photoacoustic imaging system.
AB  - BACKGROUND: Osteoarthritis is not only a disease of articular cartilage, but also
      of subchondral bone. It is difficult for ultrasound to evaluate subchondral bone
      because of permeability. This study aimed to evaluate sequential osteoarthritic
      changes of articular cartilage and subchondral bone from immobilized knees in
      rats with a photoacoustic (PA) imaging system. METHODS: The unilateral knee
      joints of adult male rats were immobilized with an internal fixator (IM group)
      for 4 and 8 weeks. Sham operated animals had holes drilled in the femur and tibia
      and screws inserted without a plate (control group). A whole proximal third of
      the tibia was obtained. The specimens were immersed in normal saline and scanned
      by the PA imaging system, which can create both ultrasound (US) and PA imaging.
      After the scanning, specimens were fixed with paraformaldehyde, decalcified and
      embedded in paraffin. Thinly sliced tissues were prepared for histological
      evaluation. PA signals from the articular cartilage and subchondral bone were
      independently evaluated. RESULTS: Gross observations showed that fibrillation
      occurred in the superficial layers and permeability of the articular cartilage
      increased. Histological observations showed that the articular cartilage became
      thicker and the bone marrow space expanded during immobilization. US images by
      the PA imaging system could evaluate the articular cartilage. PA signals from the
      articular cartilage and subchondral bone increased with the duration of
      immobilization and the difference, compared to the control group, was
      significant. CONCLUSIONS: The PA imaging system could evaluate articular
      cartilage and subchondral bone simultaneously.

PMID- 25592030
TI  - Physician practices in requesting stool samples for patients with acute
      gastroenteritis, France, August 2013-July 2014.
AB  - A better understanding of physician practices in requesting stool samples for
      patients with acute gastroenteritis (AG) is needed to more accurately interpret
      laboratory-based surveillance data. A survey was conducted in General
      Practitioners (GPs) between August 2013 and July 2014 to estimate the proportion
      of stool samples requested for patients with AG and to identify factors
      associated with GP requests for a stool sample. National health insurance (NHI)
      data together with surveillance data from a French Sentinel GP network were also
      used to estimate the proportion of stool samples requested. This proportion was
      estimated at 4.3% in the GP survey and 9.1% (95% confidence interval 8.7-9.6)
      using NHI data. Multivariate analysis indicated that the ratio of stool samples
      requested was almost five times higher in patients with bloody diarrhoea and 10
      20 times higher in patients with a long duration of illness before consultation.
      Laboratory-based surveillance data underestimates the actual burden of disease as
      fewer than one in 10 AG cases consulting their GP will be requested to submit a
      stool sample for laboratory testing. This underestimation varies by pathogen as
      stool samples are more frequently requested for severe illness. 

PMID- 25592031
TI  - Editorial for SEED 2014 Special Issue.

PMID- 25592034
TI  - Engineering living functional materials.
AB  - Natural materials, such as bone, integrate living cells composed of organic
      molecules together with inorganic components. This enables combinations of
      functionalities, such as mechanical strength and the ability to regenerate and
      remodel, which are not present in existing synthetic materials. Taking a cue from
      nature, we propose that engineered 'living functional materials' and 'living
      materials synthesis platforms' that incorporate both living systems and inorganic
      components could transform the performance and the manufacturing of materials. As
      a proof-of-concept, we recently demonstrated that synthetic gene circuits in
      Escherichia coli enabled biofilms to be both a functional material in its own
      right and a materials-synthesis platform. To demonstrate the former, we
      engineered E. coli biofilms into a chemical-inducer-responsive electrical switch.
      To demonstrate the latter, we engineered E. coli biofilms to dynamically organize
      biotic-abiotic materials across multiple length scales, template gold nanorods,
      gold nanowires, and metal/semiconductor heterostructures, and synthesize
      semiconductor nanoparticles (Chen, A. Y. et al. (2014) Synthesis and patterning
      of tunable multiscale materials with engineered cells. Nat. Mater. 13, 515-523.).
      Thus, tools from synthetic biology, such as those for artificial gene regulation,
      can be used to engineer the spatiotemporal characteristics of living systems and
      to interface living systems with inorganic materials. Such hybrids can possess
      novel properties enabled by living cells while retaining desirable
      functionalities of inorganic systems. These systems, as living functional
      materials and as living materials foundries, would provide a radically different
      paradigm of materials performance and synthesis-materials possessing
      multifunctional, self-healing, adaptable, and evolvable properties that are
      created and organized in a distributed, bottom-up, autonomously assembled, and
      environmentally sustainable manner. 

PMID- 25592036
TI  - Building immunity to cancer with radiation therapy.
AB  - Over the last decade there has been a dramatic shift in the focus of cancer
      research toward understanding how the body's immune defenses can be harnessed to
      promote the effectiveness of cytotoxic anti-cancer therapies. The ability of
      ionizing radiation to elicit anti-cancer immune responses capable of controlling
      tumor growth has led to the emergence of promising combination-based radio
      immunotherapeutic strategies for the treatment of cancer. Herein we review the
      immunoadjuvant properties of localized radiation therapy and discuss how
      technological advances in radio-oncology and developments in the field of tumor
      immunotherapy have started to revolutionize the therapeutic application of
      radiotherapy. 

PMID- 25592035
TI  - Intersection of mTOR and STAT signaling in immunity.
AB  - Optimal regulation of immune networks is essential for the generation of
      effective immune responses, and defects in such networks can lead to
      immunodeficiency while uncontrolled responses can result in autoimmune disorders.
      mTOR and STAT signaling cascades are key regulators of the differentiation and
      function of cells of the immune system. Both pathways act as sensors and
      transducers of environmental stimuli, and recent evidence has revealed points of
      crosstalk between these pathways, highlighting synergistic regulation of immune
      cell differentiation and function. We review here the current understanding of
      mTOR and STAT interactions in T cells and innate immune cells, and discuss
      potential mechanisms underlying these events. We further outline models for the
      intersection of these pathways in the regulation of immunity and highlight
      important areas for future research. 

PMID- 25592037
TI  - Hypoxia enhances migration and invasion in glioblastoma by promoting a
      mesenchymal shift mediated by the HIF1alpha-ZEB1 axis.
AB  - Glioblastoma (GBM) is the most common brain tumor in adults and the mesenchymal
      GBM subtype was reported to be the most malignant, presenting severe hypoxia and
      necrosis. Here, we investigated the possible role of a hypoxic microenvironment
      for inducing a mesenchymal and invasive phenotype. The exposure of non
      mesenchymal SNB75 and U87 cells to hypoxia induced a strong change in cell
      morphology that was accompanied by enhanced invasive capacity and the acquisition
      of mesenchymal marker expression. Further analyses showed the induction of
      HIF1alpha and HIF2alpha by hypoxia and exposure to digoxin, a cardiac glycoside
      known to inhibit HIF1/2 expression, was able to prevent hypoxia-induced
      mesenchymal transition. ShRNA-mediated knockdown of HIF1alpha, and not HIF2alpha,
      prevented this transition, as well as the knockdown of the EMT transcription
      factor ZEB1. We provide further evidence for a hypoxia-induced mesenchymal shift
      in GBM primary material by showing co-localization of GLUT1, ZEB1 and the
      mesenchymal marker YKL40 in hypoxic regions of the tumor. Collectively, our
      results identify a HIF1alpha-ZEB1 signaling axis that promotes hypoxia induced
      mesenchymal shift and invasion in GBM in a cell line dependent fashion. 

PMID- 25592038
TI  - Hepatocyte nuclear factor 4 alpha promotes the invasion, metastasis and
      angiogenesis of neuroblastoma cells via targeting matrix metalloproteinase 14.
AB  - Matrix metalloproteinase 14 (MMP-14) is the only membrane-anchored MMP that plays
      critical roles in tumorigenesis and aggressiveness. However, the regulatory
      mechanisms underlying the high MMP-14 expression in neuroblastoma (NB), a highly
      malignant tumor in childhood, still remain unclear. Herein, we applied an
      integrative approach to analyze the public datasets, and identified hepatocyte
      nuclear factor 4 alpha (HNF4alpha) as a crucial transcription factor facilitating
      the MMP-14 expression in NB. In clinical NB tissues, HNF4alpha was up-regulated
      and positively correlated with MMP-14 expression, and was an independent
      prognostic factor for unfavorable outcome of patients. Luciferase reporter and
      chromatin immunoprecipitation assays indicated that HNF4alpha directly targeted
      the binding site within the MMP-14 promoter to facilitate its transcription.
      Knockdown of HNF4alpha suppressed the invasion, metastasis and angiogenesis of NB
      cells in vitro and in vivo. Conversely, ectopic expression of HNF4alpha promoted
      the invasion, metastasis and angiogenesis of NB cells. Importantly, restoration
      of MMP-14 expression prevented the tumor cells from HNF4alpha-mediated changes in
      these biological features. Taken together, HNF4alpha exhibits oncogenic activity
      that affects the aggressiveness and angiogenesis of NB through activating the
      transcription of MMP-14. 

PMID- 25592040
TI  - Therapeutic potential of targeted multifunctional nanocomplex co-delivery of
      siRNA and low-dose doxorubicin in breast cancer.
AB  - Malignant tumors remain a major health burden throughout the world, and effective
      therapeutic strategies are urgently needed. Combining gene therapy with
      chemotherapeutics in a single delivery system is more effective than co-treatment
      of cancer with individual delivery systems carrying either gene or drug. In this
      study, a multifunctional folate-decorated and pH-responsive PHD/PPF/siVEGF
      nanocomplex is developed via a self-assembly process utilizing ternary pre
      functionalized polymers with vascular endothelial growth factor targeted siRNA.
      Antitumor effects of the combination therapy are evaluated in both in vitro and
      in vivo orthotopic xenograft models of breast cancer with systemic
      administration. The improved therapeutic response was supported by the
      observation of over 70% and 55% down-regulation of VEGF mRNA expressed in vitro
      and in vivo, effective antiproliferation and inhibition of tumor spheroids in
      vitro, significant decrease in tumor microvessel density in vivo, dramatic
      increase in life span of mice with a tumor xenograft and a decrease in toxicity
      in vivo. In addition, the current studies demonstrated the potential of
      combination of antiangiogenic therapy of siVEGF and killing off tumor cells of
      DOX, with the incorporation of tumor microenvironment sensitivity and target
      modified into a single nanoparticulate formulation for profound therapeutic
      effect. 

PMID- 25592039
TI  - IFN-gamma-mediated IRF1/miR-29b feedback loop suppresses colorectal cancer cell
      growth and metastasis by repressing IGF1.
AB  - To investigate the clinicopathological significance and underlying mechanism of
      microRNA-29b (miR-29b) in colorectal cancer (CRC), the role of miR-29b was
      investigated using in vivo and in vitro assays. Luciferase reporter assays were
      conducted to determine the association between miR-29b and the insulin-like
      growth factor 1 (IGF1) 3' untranslated region (3'UTR). Chromatin
      immunoprecipitation (ChIP) assays were employed to assess the direct binding of
      interferon regulatory factor 1 (IRF1) to miR-29b. We found that interferon (IFN)
      gamma could induce miR-29b by recruiting IRF1 to binding sites in the miR-29b
      promoter. A low level of miR-29b was significantly associated with an aggressive
      phenotype. MiR-29b inhibited CRC cell growth and invasion. IGF1, an activator of
      PI3K/Akt signaling, was confirmed as a novel target of miR-29b. Moreover, miR-29b
      increased IRF1 expression, and the inhibition of miR-29b suppressed IFN-gamma
      induced apoptosis. We elucidated the potential signaling pathway, IFN
      gamma/IRF1/miR-29b/IGF1, and its implication for CRC tumorigenesis. A positive
      feedback loop between IRF1 and miR-29b may contribute to the sensitivity of CRC
      cells to IFN-gamma. Targeting miR-29b may provide a strategy for blocking CRC
      growth and metastasis. 

PMID- 25592041
TI  - Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma)
      inhibits hepatoma cell growth via downregulation of SEPT2 expression.
AB  - Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis and low
      therapeutic efficacy. Recent studies have demonstrated the therapeutic prospect
      of peroxisome proliferator-activated receptor-gamma (PPARgamma) cancer
      angiogenesis. However, the action mechanisms remain elusive. In the present
      study, by using mass spectrometry, we found that PPARgamma ligand rosiglitazone
      (RGZ) could regulate HCC cell growth by influencing various downstream factors
      and pathways. Among the altered proteins, septin 2 (SEPT2) was found to exhibit
      oncogenic function. PPARgamma overexpression could inhibit the expression of
      SEPT2, thus blocking the promoting effects of SEPT2 on HCC cell proliferation,
      invasion and its inhibitory effect on cell apoptosis. Further studies also
      indicated that SEPT2 promoted HCC cell growth via upregulation of matrix
      metalloproteinase (MMP)-2 and -9, and simultaneously inhibited the cleavage of
      caspase-3, -7, and -9. Interestingly, the effects of SEPT2 on the above factors
      could be suppressed by PPARgamma overexpression, suggesting that PPARgamma could
      inhibit HCC cell growth via regulating the expression and blocking the oncogenic
      function of SEPT2. Taken together, these results provide new evidence for the
      action mechanisms of PPARgamma in carcinogenesis of HCC, and upon further
      investigation, PPARgamma could be developed as a new target for the treatment of
      liver cancer. 

PMID- 25592042
TI  - Gelatinases-stimuli nanoparticles encapsulating 5-fluorouridine and 5-aza-2'
      deoxycytidine enhance the sensitivity of gastric cancer cells to chemical
      therapeutics.
AB  - Aberrant methylation of the transcription factor AP-2 epsilon (TFAP2E) has been
      attributed to 5-fluorouridine (5-FU) sensitivity. 5-Aza-2'-deoxycytidine (DAC),
      an epigenetic drug that inhibits DNA methylation, is able to cause reactive
      expression of TFAP2E by demethylating activity. This property might be useful in
      enhancing the sensitivity of cancer cells to 5-FU. However, the effect of DAC is
      transient because of its instability. Here, we report the use of intelligent
      gelatinases-stimuli nanoparticles (NPs) to coencapsulate and deliver DAC and 5-FU
      to gastric cancer (GC) cells. The results showed that NPs encapsulating DAC, 5
      FU, or both could be effectively internalized by GC cells. Furthermore, we found
      that the NPs enhanced the stability of DAC, resulting in improved re-expression
      of TFAP2E. Thus, the incorporation of DAC into NPs significantly enhanced the
      sensitivity of GC cells to 5-FU by inhibiting cell growth rate and inducing cell
      apoptosis. In conclusion, the results of this study clearly demonstrated that the
      gelatinases-stimuli NPs are an efficient means to simultaneously deliver
      epigenetic and chemotherapeutic drugs that may effectively inhibit cancer cell
      proliferation. 

PMID- 25592044
TI  - Design and characterization of a single channel two-liquid capacitor and its
      application to hyperelastic strain sensing.
AB  - Room temperature liquid-metal microfluidic devices are attractive systems for
      hyperelastic strain sensing. These liquid-phase electronics are intrinsically
      soft and retain their functionality even when stretched to several times their
      original length. Currently two types of liquid metal-based strain sensors exist
      for in-plane measurements: single-microchannel resistive and two-microchannel
      capacitive devices. With a winding serpentine channel geometry, these sensors
      typically have a footprint of about a square centimeter. This large footprint of
      an individual device limits the number of sensors that can be embedded into, for
      example, electronic fabric or skin. In this work we introduce an alternative
      capacitor design consisting of two liquid metal electrodes separated by a liquid
      dielectric material within a single straight channel. Using a liquid insulator
      instead of a solid elastomer enables us to tailor the system's capacitance by
      selecting high or low dielectric constant liquids. We quantify the effects of the
      electrode geometry including the diameter, spacing, and meniscus shape as well as
      the dielectric constant of the insulating liquid on the overall system's
      capacitance. We also develop a procedure for fabricating the two-liquid capacitor
      within a single straight polydiemethylsiloxane channel and demonstrate that this
      device can have about 25 times higher capacitance per sensor's base area when
      compared to two-channel liquid metal capacitors. Lastly, we characterize the
      response of this compact device to strain and identify operational issues arising
      from complex hydrodynamics near liquid-liquid and liquid-elastomer interfaces. 

PMID- 25592043
TI  - Insulin-like growth factors inhibit dendritic cell-mediated anti-tumor immunity
      through regulating ERK1/2 phosphorylation and p38 dephosphorylation.
AB  - Insulin-like growth factors (IGFs) can promote tumorigenesis via inhibiting the
      apoptosis of cancer cells. The relationship between IGFs and dendritic cell (DC)
      mediated immunity were investigated. Advanced-stage ovarian carcinoma patients
      were first evaluated to show higher IGF-1 and IGF-2 concentrations in their
      ascites than early-stage patients. IGFs could suppress DCs' maturation, antigen
      presenting abilities, and the ability to activate antigen-specific CD8(+) T cell.
      IGF-treated DCs also secreted higher concentrations of IL-10 and TNF-alpha. IGF
      treated DCs showed decreased ERK1/2 phosphorylation and reduced p38
      dephosphorylation. The percentages of matured DCs in the ascites were
      significantly lower in the IGF-1 or IGF-2 highly-expressing WF-3 tumor-bearing
      mice. The IGF1R inhibitor - NVP-AEW541, could block the effects of IGFs to rescue
      DCs' maturation and to restore DC-mediated antigen-specific immunity through
      enhancing ERK1/2 phosphorylation and p38 dephosphorylation. IGFs can inhibit DC
      mediated anti-tumor immunity through suppressing maturation and function and the
      IGF1R inhibitor could restore the DC-mediated anti-tumor immunity. Blockade of
      IGFs could be a potential strategy for cancer immunotherapy. 

PMID- 25592045
TI  - Rating depression over brief time intervals with the Hamilton Depression Rating
      Scale: standard vs. abbreviated scales.
AB  - Although antidepressant trials typically use weekly ratings to examine changes in
      symptoms over six to 12 weeks, antidepressant treatments may improve symptoms
      more quickly. Thus, rating scales must be adapted to capture changes over shorter
      intervals. We examined the use of the 17-item Hamilton Depression Rating Scale
      (HDRS) to evaluate more rapid changes. Data were examined from 58 patients with
      major depressive disorder or bipolar disorder enrolled in double-blind, placebo
      controlled, crossover studies who received a single infusion of ketamine (0.5
      mg/kg) or placebo over 40 min then crossed over to the other condition. HDRS
      subscales, a single HDRS Depressed mood item, and a visual analogue scale were
      used at baseline, after a brief interval (230 min), and one week post-infusion.
      Effect sizes for the ketamine-placebo difference were moderate (d > 0.50), but
      one and two-item HDRS subscales had the smallest effects. Response rates on
      active drug were lowest for the complete HDRS (43%); the remaining scales had
      higher response rates to active drug, but the shortest subscales had higher
      response rates to placebo. Correlations between the changes from baseline to 230
      min post-ketamine across scores were similar for most subscales (r = 0.82-0.97),
      but correlations using the single items were lower (r < 0.74). Overall, effect
      sizes for drug-placebo differences and correlations between changes were lower
      for one- and two-item measures. Response rates were lower with the full HDRS
      scale. The data suggest that, to best identify rapid antidepressant effects, a
      scale should have more than two items, but fewer items than a full scale.

PMID- 25592047
TI  - Interactions of the renin-angiotensin system in colorectal cancer and metastasis.
AB  - The novel function of the renin-angiotensin system (RAS) is cardiovascular
      homeostasis. While the major active mediator angiotensin II (ANG II) produces
      most of the physiologic responses via angiotensin II type I receptor (AT1R),
      recent insights have looked at the implications of ANG II and its impact on solid
      tumor formation. Preclinical studies have demonstrated the direct effect of ANG
      II on the stimulation of angiogenesis via VEGF and other proliferative mediators.
      RAS components have thus been identified in numerous malignant tissues.
      Inhibition of the AT1R via angiotensin-converting enzyme inhibitors (ACE-Is) has
      demonstrated a decrease in solid tumor development and metastasis. Numerous
      retrospective analyses have demonstrated a reduction in colorectal cancer
      incidence, polyp formation, and distant metastasis in patients taking inhibitors
      of the RAS. The use of commonly prescribed anti-hypertensive medications as a
      chemo-preventative medication may have a remarkable impact in the colorectal
      cancer community. Further investigation and prospective clinical trials may
      provide further insight into the potentially beneficial use of ACE-Is and their
      impact on colorectal cancer. 

PMID- 25592048
TI  - Coadministration of basic fibroblast growth factor-loaded polycaprolactone beads
      and autologous myoblasts in a dog model of fecal incontinence.
AB  - PURPOSE: Basic fibroblastic growth factor (bFGF), a member of the heparin-binding
      growth factor family, regulates muscle differentiation. We investigated whether
      coadministration of autologous myoblasts and bFGF-loaded polycaprolactone beads
      could improve sphincter recovery in a dog model of fecal incontinence (FI).
      METHODS: FI was induced by resecting 25% of the posterior anal sphincter in ten
      mongrel dogs. One month later, the dogs were randomized to receive either PKH-26
      labeled autologous myoblasts alone (M group, five dogs) or autologous myoblasts
      and bFGF-loaded polycaprolactone beads (MBG group, five dogs). The outcomes
      included anal manometry, compound muscle action potentials (CMAPs) of the
      pudendal nerve, and histology. RESULTS: The increase in anal contractile pressure
      over 3 months was significantly greater in the MBG group (from 4.85 to 6.83 mmHg)
      than that in the M group (from 4.94 to 4.25 mmHg), with a coefficient for the
      difference in recovery rate of 2.672 (95% confidence interval [CI] 0.962 to
      4.373, p = 0.002). The change in the CMAP amplitude was also significantly
      greater in the MBG group (from 0.59 to 1.56 mV) than that in the M group (from
      0.81 to 0.67 mV) (coefficient 1.114, 95% CI 0.43 to 1.80, p = 0.001). Labeled
      cells were detected in 2/5 (40%) and 5/5 (100%) dogs in the M and MBG groups,
      respectively. CONCLUSION: Coadministration of bFGF-loaded PCL beads and
      autologous myoblasts improved the recovery of sphincter function in a dog model
      of FI and had better outcomes than cell-based therapy alone.

PMID- 25592049
TI  - 3D spherical microtissues and microfluidic technology for multi-tissue
      experiments and analysis.
AB  - Rational development of more physiologic in vitro models includes the design of
      robust and flexible 3D-microtissue-based multi-tissue devices, which allow for
      tissue-tissue interactions. The developed device consists of multiple
      microchambers interconnected by microchannels. Pre-formed spherical microtissues
      are loaded into the microchambers and cultured under continuous perfusion.
      Gravity-driven flow is generated from on-chip reservoirs through automated chip
      tilting without any need for additional tubing and external pumps. This tilting
      concept allows for operating up to 48 devices in parallel in order to test
      various drug concentrations with a sufficient number of replicates. For a proof
      of concept, rat liver and colorectal tumor microtissues were interconnected on
      the chip and cultured during 8 days in the presence of the pro-drug
      cyclophosphamide. Cyclophosphamide has a significant impact on tumor growth but
      only after bio-activation by the liver. This effect was only observed in the
      perfused and interconnected co-cultures of different microtissue types on-chip,
      whereas the discontinuous transfer of supernatant via pipetting from static liver
      microtissues that have been treated with cyclophosphamide did not significantly
      affect tumor growth. The results indicate the utility and multi-tissue
      functionality of this platform. The importance of continuous medium circulation
      and tissue interaction is highlighted. 

PMID- 25592050
TI  - In vitro co-culture model of medulloblastoma and human neural stem cells for drug
      delivery assessment.
AB  - Physiologically relevant in vitro models can serve as biological analytical
      platforms for testing novel treatments and drug delivery systems. We describe the
      first steps in the development of a 3D human brain tumour co-culture model that
      includes the interplay between normal and tumour tissue along with nutrient
      gradients, cell-cell and cell-matrix interactions. The human medulloblastoma cell
      line UW228-3 and human foetal brain tissue were marked with two supravital
      fluorescent dyes (CDCFDASE, Celltrace Violet) and cultured together in ultra-low
      attachment 96-well plates to form reproducible single co-culture spheroids (d =
      600 MUm, CV% = 10%). Spheroids were treated with model cytotoxic drug etoposide
      (0.3-100 MUM) and the viability of normal and tumour tissue quantified separately
      using flow cytometry and multiphoton microscopy. Etoposide levels of 10 MUM were
      found to maximise toxicity to tumours (6.5% viability) while stem cells
      maintained a surviving fraction of 40%. The flexible cell marking procedure and
      high-throughput compatible protocol make this platform highly transferable to
      other cell types, primary tissues and personalised screening programs. The
      model's key anticipated use is for screening and assessment of drug delivery
      strategies to target brain tumours, and is ready for further developments, e.g.
      differentiation of stem cells to a range of cell types and more extensive
      biological validation.

PMID- 25592051
TI  - Oral contraceptive use and saliva diurnal pattern of metabolic steroid hormones
      in young healthy women.
AB  - BACKGROUND: The impact of oral contraceptives (OCs) on the saliva diurnal pattern
      of metabolic steroid hormones remained unknown. STUDY DESIGN: Saliva samples were
      taken from young healthy women (11 OC users, 10 non-OC users) to analyze
      cortisol, dehydroepiandrosterone (DHEA) and testosterone 4 times (days 1, 8, 15
      and 22) over one menstrual cycle. RESULTS: OC use decreased saliva testosterone
      concentrations (p<.01) under all conditions of day and time, but not saliva
      cortisol. OC also decreased saliva DHEA concentrations during the first part of
      the day (p<.05), with a dampened amplitude in its diurnal pattern. CONCLUSION:
      The clinical relevance requires further study.

PMID- 25592052
TI  - Acute traumatic patellar dislocation.
AB  - Inaugural traumatic patellar dislocation is most often due to trauma sustained
      during physical or sports activity. Two-thirds of acute patellar dislocations
      occur in young active patients (less than 20 years old). Non-contact knee sprain
      in flexion and valgus is the leading mechanism in patellar dislocation,
      accounting for as many as 93% of all cases. The strong displacement of the
      patella tears the medial stabilizing structures, and notably the medial
      patellofemoral ligament (MPFL), which is almost always injured in acute patellar
      dislocation, most frequently at its femoral attachment. Lateral patellar glide
      can be assessed with the knee in extension or 20 degrees  flexion. Displacement
      by more than 50% of the patellar width is considered abnormal and may induce
      apprehension. Plain X-ray and CT are mandatory to diagnose bony risk factors for
      patellar dislocation, such as trochlear dysplasia or increased tibial tubercle
      trochlear groove distance (TT-TG), and plan correction. MRI gives information on
      cartilage and capsulo-ligamentous status for treatment planning: free bodies or
      osteochondral fracture have to be treated surgically. If patellar dislocation
      occurs in an anatomically normal knee and osteochondral fracture is ruled out on
      MRI, non-operative treatment is usually recommended.

PMID- 25592053
TI  - Cleidocranial dysplasia with bilateral posterior glenohumeral dislocation: a case
      report.
AB  - A 31-year-old man experienced bilateral posterior glenohumeral dislocation during
      seizures. He had cleidocranial dysplasia with complete absence of both clavicles.
      Cleidocranial dysplasia is a rare inherited disease also known as Marie-Sainton
      syndrome and responsible for dental abnormalities well-known to stomatologists
      and dentists. Other manifestations include defective development of the skull
      bones and hypoplastic or aplastic clavicles. We found no previous reports of
      bilateral posterior glenohumeral dislocation in patients with cleidocranial
      dysplasia. The objective of this work was to look for an association between
      clavicular aplasia and posterior glenohumeral dislocation.

PMID- 25592046
TI  - Association of lifestyle and cardiovascular risk factors with lung function in a
      sample of the adult Italian population: a cross-sectional survey.
AB  - BACKGROUND: Some epidemiological studies have identified high values of pulmonary
      functions as an indicator of good health. At present little is known about the
      distribution of these characteristics in the general adult population. OBJECTIVE:
      The aim of this study is to describe pulmonary function in the Italian general
      population and to evaluate its association with some lifestyle and cardiovascular
      risk conditions using data of the OEC/HES (Cardiovascular Epidemiology
      Observatory/Health Examination Survey) Project, a cross-sectional survey based on
      the examination of random samples of the general population. METHODS: A total of
      9,108 men and women aged 35-79 years were examined between 2008 and 2012.
      Pulmonary function [forced expiratory volume in 1 s (FEV1) and forced vital
      capacity (FVC)] was measured with a spirometer and anthropometric measurements
      and blood pressure were also recorded, whereas lifestyle (physical activity,
      smoking habits), health status and drug treatment were assessed by a
      questionnaire. FEV1 and FVC % predicted were also calculated. Univariate analysis
      and a multiple linear regression were performed in order to assess associations.
      RESULTS: FVC and FEV1 percent predicted values were 98.0 (95% CI 97.4-98.6) and
      107.3 (95% CI 106.6-107.9) for men and 108.7 (95% CI 107.9-109.4) and 113.3 (95%
      CI 112.6-114.1) for women. A lower mean FEV1 and FVC % predicted value was found
      in smokers, individuals physically inactive during their leisure time, diabetics,
      obese individuals and hypertensive patients. Multivariate linear regression
      models confirmed the independent association between risk factors and FEV1 and
      FVC levels. CONCLUSION: Our data confirm the inverse relationship existing
      between pulmonary function and cardiovascular risk factors, obesity,
      dyslipidemias and hypertension, all of which are conditions related to chronic
      diseases. An early public healthcare intervention on lifestyle could be useful to
      reduce the decline in pulmonary function.

PMID- 25592055
TI  - A comparison of two approaches for representing AAC vocabulary for young
      children.
AB  - PURPOSE: Young children with complex communication needs often experience
      difficulty in using currently available graphic symbol systems as a method of
      augmentative and alternative communication (AAC). Information on young children's
      performance with graphic representations based on this population's
      conceptualizations of these vocabulary items may assist in the development of
      more effective AAC systems. METHOD: This study developed Developmentally
      Appropriate Symbols (DAS) for 10 early emerging vocabulary concepts using
      procedures designed to address both conceptual and appeal issues for graphic
      representations for young children. Using a post-test only, between-subjects
      comparison group design, 40 typically-developing 2.5-3.5-year-old children were
      randomly assigned to receive a brief training in either of two different types of
      graphic symbol sets: (a) DAS or (b) Picture Communication Symbols (PCS), a,
      commercially available graphic symbol system. RESULT: Results of a two sample
      independent t-test provide evidence that children in the DAS condition correctly
      identified more symbols than children trained with the PCS symbols. There was no
      evidence of a preference between the symbol sets. CONCLUSION: The results provide
      support for careful consideration of children's use and understanding of language
      in developing AAC systems for young children.

PMID- 25592054
TI  - Oxygen saturation index and severity of hypoxic respiratory failure.
AB  - BACKGROUND: The oxygenation index (OI = mean airway pressure, MAP * FiO2 * 100 :
      PaO2) is used to assess the severity of hypoxic respiratory failure (HRF) and
      persistent pulmonary hypertension of the newborn (PPHN). An indwelling arterial
      line or arterial punctures are necessary to obtain PaO2 for the calculation of
      OI. Oxygenation can be continuously and noninvasively assessed using pulse
      oximetry. The use of the oxygen saturation index (OSI = MAP * FiO2 * 100 : SpO2)
      can be an alternate method of assessing the severity of HRF. OBJECTIVE: To
      evaluate the correlation between OSI and OI in the following: (1) neonates with
      HRF and (2) a lamb model of meconium aspiration syndrome. METHODS: Human
      neonates: a retrospective chart review of 74 ventilated late preterm/term
      neonates with indwelling arterial access and SpO2 values in the first 24 h of
      life was conducted. OSI and OI were calculated and correlated. Lamb model:
      arterial blood gases were drawn and preductal SpO2 was documented in 40 term
      newborn lambs with asphyxia and meconium aspiration. OI and OSI were calculated
      and correlated with pulmonary vascular resistance (PVR). RESULTS: Mean values of
      OSI and OI showed a correlation coefficient of 0.952 in neonates (mean value of
      308 observations in 74 neonates) and 0.948 in lambs (mean value of 743
      observations in 40 lambs). In lambs, with increasing PVR, there was a decrease in
      OI and OSI. CONCLUSION: OSI correlates significantly with OI in infants with HRF.
      This noninvasive measure may be used to assess the severity of HRF and PPHN in
      neonates without arterial access.

PMID- 25592056
TI  - Foreword: too little, too late, too much, too long, just right? Reinforcing the
      importance of a thorough history and physical exam for correct diagnosis and
      ongoing patient management.

PMID- 25592057
TI  - Engineering the carrier dynamics of InGaN nanowire white light-emitting diodes by
      distributed p-AlGaN electron blocking layers.
AB  - We report on the demonstration of a new type of axial nanowire LED
      heterostructures, with the use of self-organized InGaN/AlGaN dot-in-a-wire core
      shell nanowire arrays. The large bandgap AlGaN shell is spontaneously formed on
      the sidewall of the nanowire during the growth of AlGaN barrier of the quantum
      dot active region. As such, nonradiative surface recombination, that dominates
      the carrier dynamics of conventional axial nanowire LED structures, can be
      largely eliminated, leading to significantly increased carrier lifetime from ~0.3
      ns to 4.5 ns. The luminescence emission is also enhanced by orders of magnitude.
      Moreover, the p-doped AlGaN barrier layers can function as distributed electron
      blocking layers (EBLs), which is found to be more effective in reducing electron
      overflow, compared to the conventional AlGaN EBL. The device displays strong
      white-light emission, with a color rendering index of ~95. An output power of >5
      mW is measured for a 1 mm * 1 mm device, which is more than 500 times stronger
      than the conventional InGaN axial nanowire LEDs without AlGaN distributed EBLs.

PMID- 25592058
TI  - Microwave ablation versus transarterial chemoembolization in large hepatocellular
      carcinoma: prospective analysis.
AB  - OBJECTIVE: Limited therapies are offered for large hepatocellular carcinoma
      (HCC). It carries dismal prognosis and efforts tried changing its management from
      a palliative to a curative mode. Transarterial chemoembolization (TACE) is a
      palliative procedure that may have survival benefit if compared to non-management
      of large lesions. Microwave ablation (MWA) has emerged as a relatively new
      technique with promise of larger and faster ablation. We aim to evaluate the
      efficacy and safety of percutaneous MWA versus TACE for large tumors (5-7 cm) and
      to assess their effects on local tumor progression and survival. PATIENTS AND
      METHODS: Sixty-four patients with large lesions are managed in our
      multidisciplinary HCC clinic and were divided into two groups treated either by
      MWA or TACE. Complete response rate, local recurrence, de novo lesions, and
      overall survival analysis are compared between both procedures. RESULTS: Both
      groups were comparable as regards the demographic and ultrasonographic features.
      MWA showed higher rates of complete ablation (75%) with fewer sessions, lower
      incidence of tumor recurrence (p = 0.02), development of de novo lesions (p =
      0.03), occurrence of post-treatment ascites (p = 0.003), and higher survival
      rates (p = 0.04). The mean survival of the microwave group was 21.7 months with
      actuarial probability of survival at 12 and 18 months 78.2% and 68.4%,
      respectively. The mean survival of the TACE group was 13.7 months with actuarial
      probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively.
      CONCLUSION: MWA showed better results than TACE in the management of large HCC
      lesions.

PMID- 25592060
TI  - Photoswitchable semiconductor nanocrystals with self-regulating photochromic
      Forster resonance energy transfer acceptors.
AB  - Photoswitchable molecules and nanoparticles constitute superior biosensors for a
      wide range of industrial, research and biomedical applications. Rendered
      reversible by spontaneous or deterministic means, such probes facilitate many of
      the techniques in fluorescence microscopy that surpass the optical resolution
      dictated by diffraction. Here we have devised a family of photoswitchable quantum
      dots (psQDs) in which the semiconductor core functions as a fluorescence donor in
      Forster resonance energy transfer (FRET), and multiple photochromic
      diheteroarylethene groups function as acceptors upon activation by ultraviolet
      light. The QDs were coated with a polymer bearing photochromic groups attached
      via linkers of different length. Despite the resulting nominal differences in
      donor-acceptor separation and anticipated FRET efficiencies, the maximum
      quenching of all psQD preparations was 38+/-2%. This result was attributable to
      the large ultraviolet absorption cross-section of the QDs, leading to
      preferential cycloreversion of photochromic groups situated closer to the
      nanoparticle surface and/or with a more favourable orientation. 

PMID- 25592059
TI  - AML with gain of chromosome 8 as the sole chromosomal abnormality (+8sole) is
      associated with a specific molecular mutation pattern including ASXL1 mutations
      in 46.8% of the patients.
AB  - Trisomy 8 is the most frequent cytogenetically gained aberration in AML. We
      compared 79 adult de novo AML with trisomy 8 as the sole cytogenetic abnormality
      (+8sole) to 511 normal karyotype AML patients (NK). +8sole patients were older
      (p=0.013), presented lower WBC counts (p=0.010), harbored more often ASXL1
      mutations (p<0.001) and RUNX1 mutations (p=0.009), but less frequent FLT3-ITD
      (p=0.038), NPM1 mutations (p<0.001) and double-mutated CEBPA (p=0.038) than NK
      patients. No prognostic difference was found between +8sole and NK. With respect
      to genetic stability we found +8sole was instable, and molecular markers were
      either stable or gained in number and diversity.

PMID- 25592061
TI  - Updating the surgical management of peritoneal carcinomatosis in patients with
      neuroendocrine tumors.
AB  - Well-differentiated digestive neuroendocrine tumors (NET) are a heterogeneous
      group of neoplasms usually associated with slow growth but a high rate of
      metastases, including peritoneal carcinomatosis (PC). Herein, we aimed to
      comprehensively review the current knowledge of PC in terms of implications for
      the management and prognosis of patients with NET, including the latest studies
      and expert statements. NET-derived PC concerns about 17% of NET patients and up
      to 30% of those with small intestine primary NET. It has an independent
      pejorative prognostic impact. The extent of PC in NET patients and its severity
      can be expressed by analogy to other malignancies. However, it must be placed in
      the context of NET disorders, which usually vary from other PC-related
      malignancies. Recently, a gravity PC score was proposed by a consensus European
      Neuroendocrine Tumor Society (ENETS) expert group, but it requires validation. In
      addition, the form of peritoneal involvement (nodular or fusiform/infiltrative)
      might influence its prognosis and management. Aggressive surgical management
      seems justified for subsets of NET-related PC but requires careful selection of
      the candidates most likely to benefit. Cytoreductive surgery prolongs survival,
      especially when the peritoneal lesions are completely resected. Too little is
      known about the benefit of hyperthermic intraperitoneal chemotherapy for NET
      derived PC, but if it confers an advantage, it would have to be counterbalanced
      by its high morbidity.

PMID- 25592063
TI  - [In Process Citation].
AB  - A large variety of local anaesthetics is widely used in dental clinic. Cautious
      application is essential in order to avoid adverse events of potentially lethal
      nature. The objective of this article is to present an overview of the mechanisms
      and to underline potentially lethal adverse effects and contraindications. The
      knowledge of specific side effects is vital in daily practice. An overview on
      specific products is accessible on www.kompendium.ch, however users have to be
      aware of the fact that this source may be incomplete. 

PMID- 25592062
TI  - The emerging role of microRNAs in resistance to lung cancer treatments.
AB  - One of the major challenges in the treatment of lung cancer is the development of
      drug resistance. This represents a major obstacle in the treatment of patients,
      limiting the efficacy of both conventional chemotherapy and biological therapies.
      Deciphering the mechanisms of resistance is critical to further understanding the
      multifactorial pathways involved, and in developing more specific targeted
      treatments. To date, numerous studies have reported the potential role of
      microRNAs (miRNAs) in resistance to various cancer treatments. MicroRNAs are a
      family of small non-coding RNAs that regulate gene expression by sequence
      specific targeting of mRNAs causing translational repression or mRNA degradation.
      More than 1200 validated human miRNAs have been identified to date. While as
      little as one miRNA can regulate hundreds of targets, a single target can also be
      affected by multiple miRNAs. Evidence suggests that dysregulation of specific
      miRNAs may be involved in the acquisition of resistance to a number of cancer
      treatments, thereby modulating the sensitivity of cancer cells to such therapies.
      Therefore, targeting miRNAs may be an attractive strategy for developing novel
      and more effective individualized therapies, improving drug efficiency, and for
      predicting patient response to different treatments. In this review, we provide
      an overview on the role of miRNAs in resistance to current lung cancer therapies
      and novel biological agents. 

PMID- 25592064
TI  - Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP
      overexpressing breast carcinoma cells.
AB  - ABT-737, a BH3-mimetic small-molecule inhibitor, binds with very high affinity to
      Bcl-2, Bcl-xL and Bcl-w, and inhibits their activity. Aurora kinase is one of the
      serine/threonine kinase family members and is a vital and critical regulator of
      mitosis and meiosis. In the present study, we investigated the effects and
      mechanisms of a combined treatment of ABT-737 and VX-680 (Aurora kinase
      inhibitor) in human breast cancer MDA-MB-435S cells. ABT-737 plus VX-680 induced
      caspase-dependent apoptosis in the human breast cancer cells. Combined treatment
      with ABT-737 and VX-680 led to the downregulation of Bcl-2 expression at the
      transcriptional level and the downregulation of c-FLIP and Mcl-1 expression at
      the post-transcriptional level. Overexpression of Bcl-2 or c-FLIP could not block
      the induction of apoptosis caused by the combined treatment with ABT-737 and VX
      680. However, overexpression of Mcl-1 partially inhibited the induction of
      apoptosis. In contrast, the combined treatment with ABT-737 and VX680 had no
      effect on the apoptosis in normal cells. Taken together, our study demonstrated
      that combined treatment with ABT-737 and VX-680 induced apoptosis in anti
      apoptotic protein (Bcl-2 or c-FLIP)-overexpressing cells. 

PMID- 25592065
TI  - A dynamic Cassie-Baxter model.
AB  - Contact-angle hysteresis of a liquid suspended on surface microstructures, namely
      in a Cassie-Baxter state, is determined mainly by the receding contact line
      although not fully understood. Existing modified Cassie-Baxter models predict
      some but not most experimental data in the literature. Noting that most models
      were based on the two-dimensional (2-D) principle whereas the experiments were
      under three-dimensional (3-D) conditions, here we develop a 2-D experiment. While
      3-D experiments measure the receding contact lines averaged over space and time,
      2-D experiments eliminate the spatial averaging and can further eliminate the
      temporal averaging by high-speed visualization. The resulting details of the
      contact line motion lead us to propose a 2-D model, which incorporates the
      contact-line friction. The new 2-D model matches the 2-D experimental results
      excellently while all existing models show significant deviation. By introducing
      a line solid fraction term, the 2-D model is further generalized to a 3-D model,
      which successfully predicts a wide range of 3-D data in the literature regardless
      of their distinct microstructures and receding modes. 

PMID- 25592066
TI  - Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2
      signalling in prostate cancer cells.
AB  - BACKGROUND: Androgens drive the onset and progression of prostate cancer (PCa)
      via androgen receptor (AR) signalling. The principal treatment for PCa is
      androgen deprivation therapy, although the majority of patients eventually
      develop a lethal castrate-resistant form of the disease, where despite low serum
      testosterone levels AR signalling persists. Advanced PCa often has hyper
      activated RAS/ERK1/2 signalling thought to be due to loss of function of key
      negative regulators of the pathway, the details of which are not fully
      understood. METHODS: We recently carried out a genome-wide study and identified a
      subset of 226 novel androgen-regulated genes (PLOS ONE 6:e29088, 2011). In this
      study we have meta-analysed this dataset with genes and pathways frequently
      mutated in PCa to identify androgen-responsive regulators of the RAS/ERK1/2
      pathway. RESULTS: We find the PTGER4 and TSPYL2 genes are up-regulated by
      androgen stimulation and the ADCY1, OPKR1, TRIB1, SPRY1 and PTPRR are down
      regulated by androgens. Further characterisation of PTPRR protein in LNCaP cells
      revealed it is an early and direct target of the androgen receptor which
      negatively regulates the RAS/ERK1/2 pathway and reduces cell proliferation in
      response to androgens. CONCLUSION: Our data suggest that loss of PTPRR in
      clinical PCa is one factor that might contribute to activation of the RAS/ERK1/2
      pathway.

PMID- 25592068
TI  - The mammalian olivocochlear system--a legacy of non-cerebellar research in the
      Mugnaini lab.
AB  - Although the major emphasis of Enrico Mugnaini's research has been on
      investigations of the cerebellum, a significant amount of work over a relatively
      short span of time was also done in his lab on a number of other brain systems.
      These centered on sensory systems. One of these extra-cerebellar systems that he
      embraced was the auditory system. Portions of the cochlear nucleus, the first
      synaptic relay station along the central auditory pathways, possess a cerebellar
      like circuitry and neurochemistry, and this no doubt lured Enrico into the
      auditory field. As new tools became available to pursue neuroanatomical research
      in general, which included a novel antibody to glutamic acid decarboxylase (GAD),
      Enrico's lab soon branched out into investigating many other brain structures
      beyond the cerebellum, with an overall goal of producing a map illustrating GAD
      expression in the brain. In collaboration with long-term colleagues, one of these
      many non-cerebellar regions he took an interest in was an efferent pathway
      originating in the superior olive and projecting to the cochlea, the peripheral
      end organ for hearing. There was a need for a more complete neurochemical map of
      this olivocochlear efferent system, and armed with new antibodies and well
      established tract tracing tools, together we set out to further explore this
      system. This short review describes the work done with Enrico on the
      olivocochlear system of rodents, and also continues the story beyond Enrico's lab
      to reveal how the work done in his lab fits into the larger scheme of current,
      ongoing research into the olivocochlear system. 

PMID- 25592069
TI  - Neurog1 Genetic Inducible Fate Mapping (GIFM) Reveals the Existence of Complex
      Spatiotemporal Cyto-Architectures in the Developing Cerebellum.
AB  - Neurog1 is a pro-neural basic helix-loop-helix (bHLH) transcription factor
      expressed in progenitor cells located in the ventricular zone and subsequently
      the presumptive white matter tracts of the developing mouse cerebellum. We used
      genetic inducible fate mapping (GIFM) with a transgenic Neurog1-CreER allele to
      characterize the contributions of Neurog1 lineages to cerebellar circuit
      formation in mice. GIFM reveals Neurog1-expressing progenitors are fate-mapped to
      become Purkinje cells and all GABAergic interneuron cell types of the cerebellar
      cortex but not glia. The spatiotemporal sequence of GIFM is unique to each
      neuronal cell type. GIFM on embryonic days (E) 10.5 to E12.5 labels Purkinje
      cells with different medial-lateral settling patterns depending on the day of
      tamoxifen delivery. GIFM on E11.5 to P7 labels interneurons and the timing of
      tamoxifen administration correlates with the final inside-to-outside resting
      position of GABAergic interneurons in the cerebellar cortex. Proliferative status
      and long-term BrdU retention of GIFM lineages reveals Purkinje cells express
      Neurog1 around the time they become post-mitotic. In contrast, GIFM labels
      mitotic and post-mitotic interneurons. Neurog1-CreER GIFM reveals a correlation
      between the timing of Neurog1 expression and the spatial organization of
      GABAergic neurons in the cerebellar cortex with possible implications for
      cerebellar circuit assembly. 

PMID- 25592070
TI  - Substantia nigra echogenicity in hereditary ataxias with and without
      nigrostriatal pathology: a pilot study.
AB  - Our objective was to determine whether substantia nigra (SN) hyperechogenicity is
      greater in spinocerebellar ataxias (SCA) with nigrostriatal affectation than in
      ataxias without it. A cross-sectional case-control study analyzing four groups of
      patients was conducted: 1) nigrostriatal ataxias (SCA3 and SCA6), 2)
      nigrostriatal healthy controls matched by age and sex, 3) non-nigrostriatal
      ataxias (FRDA and SCA7), and 4) non-nigrostriatal healthy controls matched by age
      and sex. All the patients underwent a transcranial ultrasound performed by an
      experienced sonographer blinded to the clinical, genetic, and neuroimaging data.
      The SN area was measured and compared in the four groups. The SN area was also
      correlated with clinical features and genetic data in the two ataxia groups. We
      examined 12 patients with nigrostriatal ataxia (11 SCA3 and 1 SCA6), 12
      nigrostriatal healthy control patients, 7 patients with non-nigrostriatal ataxia
      (5 FRDA and 2 SCA7), and 7 non-nigrostriatal healthy control patients. The median
      (IQR) SN area (cm(2)) was greater in the nigrostriatal ataxias compared with the
      controls (right SN, 0.43 [0.44] vs. 0.11 [0.25]; P=0.001; left SN, 0.32 [0.25]
      vs. 0.11 [0.16]; P=0.001), but was similar among the non-nigrostriatal ataxias
      and controls. There were no statistically significant differences in the SN area
      between the nigrostriatal and non-nigrostriatal ataxias, although there was a
      tendency for a greater left SN area in the nigrostriatal compared with the non
      nigrostriatal ataxias (0.32 [0.25] vs. 0.16 [0.24], P=0.083). SN echogenicity is
      markedly greater in ataxias with nigrostriatal pathology than in controls. The
      role of SN hyperechogenicity in differentiating ataxias with and without
      nigrostriatal pathology should be elucidated in future studies.

PMID- 25592071
TI  - Clinical and Neuropathological Features of Spastic Ataxia in a Spanish Family
      with Novel Compound Heterozygous Mutations in STUB1.

PMID- 25592072
TI  - Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in
      the Developing Cerebellum.
AB  - Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal
      alcohol spectrum disorders. The cerebellum is one of the brain areas that are
      most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains
      unclear. Our previous in vitro studies have shown that the double-stranded RNA
      (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol
      exposure and ethanol activates PKR through association with its intracellular
      activator RAX. However, the role of PKR and its interaction with RAX in vivo have
      not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J
      mice with a deficient RAX-binding domain in PKR, we determined the critical role
      of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing
      cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile
      as wild-type mice, ethanol induces less brain/body mass reduction as well as
      cerebellar neuronal loss. In addition, ethanol promotes interleukin-1beta (IL
      1beta) secretion, and IL-1beta is a master cytokine regulating inflammatory
      response. Importantly, ethanol-promoted IL-1beta secretion is inhibited in the
      developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR
      activation regulate ethanol neurotoxicity in the developing cerebellum, which may
      involve ethanol-induced neuroinflammation. Further, PKR could be a possible
      target for pharmacological intervention to prevent or treat fetal alcohol
      spectrum disorder (FASD). 

PMID- 25592073
TI  - Two-component systems and toxinogenesis regulation in Clostridium botulinum.
AB  - Botulinum neurotoxins (BoNTs) are the most potent toxins ever known. They are
      mostly produced by Clostridium botulinum but also by other clostridia. BoNTs
      associate with non-toxic proteins (ANTPs) to form complexes of various sizes.
      Toxin production is highly regulated through complex networks of regulatory
      systems involving an alternative sigma factor, BotR, and at least 6 recently
      described two-component systems (TCSs). TCSs allow bacteria to sense
      environmental changes and to respond to various stimuli by regulating the
      expression of specific genes at a transcriptional level. Several environmental
      stimuli have been identified to positively or negatively regulate toxin
      synthesis; however, the link between environmental stimuli and TCSs is still
      elusive. This review aims to highlight the role of TCSs as a central point in the
      regulation of toxin production in C. botulinum. 

PMID- 25592074
TI  - Procalcitonin and long-term prognosis after an admission for acute heart failure.
AB  - BACKGROUND: Traditionally, procalcitonin (PCT) is considered a diagnostic marker
      of bacterial infections. However, slightly elevated levels of PCT have also been
      found in patients with heart failure. In this context, it has been suggested that
      PCT may serve as a proxy for underrecognized infection, endotoxemia, or
      heightened proinflammatory activity. Nevertheless, the clinical utility of PCT in
      this setting is scarce. We aimed to evaluate the association between PCT and the
      risk of long-term outcomes. METHODS AND RESULTS: We measured at admission PCT of
      261 consecutive patients admitted for acute heart failure (AHF) after excluding
      active infection. Cox and negative binomial regression methods were used to
      evaluate the association between PCT and the risk of death and recurrent
      rehospitalizations, respectively. At a median follow-up of 2years (IQR: 1.0-2.8),
      108 deaths, 170 all-cause rehospitalizations and 96 AHF-rehospitalizations were
      registered. In an adjusted analysis, including well-established risk factors such
      as natriuretic peptides and indices of renal function, the logarithm of PCT was
      associated with a higher risk of death (HR=1.43, CI 95%: 1.12-1.82; p=0.004), all
      cause rehospitalizations (IRR=1.22, CI 95% 1.02-1.44; p=0.025) and AHF
      rehospitalizations (IRR=1.28, CI 95%: 1.02-1.61; p=0.032). The association with
      these endpoints persisted after adjustment for other inflammatory biomarkers such
      as white blood cells, C-reactive protein and interleukins. CONCLUSION: In
      patients with AHF and no evidence of infection, PCT was independently and
      positively associated with the risk of long-term death and recurrent
      rehospitalizations.

PMID- 25592075
TI  - Factor V Leiden mutation and high FVIII are associated with an increased risk of
      VTE in women with breast cancer during adjuvant tamoxifen - results from a
      prospective, single center, case control study.
AB  - BACKGROUND: Estimates of the risk ratio of tamoxifen-associated venous
      thromboembolism (VTE) in breast cancer patients range from 2.4 to 7.1. The
      occurrence of thrombosis in patients with breast cancer complicates the clinical
      condition and causes a change of treatment. Our study was conducted in order to
      investigate the influence of patient-related risk factors for thrombosis
      development in breast cancer patients whose treatment included adjuvant
      tamoxifen. METHODS: The prospective, single center, case control study included
      150 breast cancer women, 50 whom developed venous thrombosis during adjuvant
      tamoxifen and 100 whom did not have thrombosis, as a control group. Patient
      related risk factors such as: age, body mass index, previous VTE, varicose veins,
      concomitant diseases, the presence of prothrombotic mutations (FV Leiden, FII
      G20210A) and FVIII activity were evaluated in both groups. RESULTS: In respect of
      prothrombotic mutations, the FV Leiden mutation was present in a higher number of
      women from the VTE group (10/50 vs 7/100; P=0.020). Additionally, FVIII activity
      was significantly higher in the VTE group; median (IQR), of 1.79 (0.69) vs 1.45
      (0.55); P<0.001 and more women in this group (24/50 vs 34/100) had increased
      FVIII activity; P=0.020. In those women with FVIII>1.5IU/ml, who were carriers of
      prothrombotic mutations, an OR of 3.76 (CI 95% 1.276-11.096; P=0.016) was
      obtained for VTE. CONCLUSION: The results of our study showed that the factor V
      Leiden mutation and high FVIII are associated with an increased risk of VTE in
      women with breast cancer during adjuvant tamoxifen.

PMID- 25592076
TI  - Synergistic effect of all-trans retinoic acid in combination with protein kinase
      C 412 in FMS-like tyrosine kinase 3-mutated acute myeloid leukemia cells.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease. Numerous molecular
      abnormalities have been identified in AML and, amongst these, FMS-like tyrosine
      kinase 3 (FLT3) mutations are one of the most common somatic alterations
      detected. In the present study, an in vitro investigation was performed to
      evaluate the effects of all-trans retinoic acid (ATRA) and PKC412, alone and in
      combination, in FLT3-mutated AML cell lines. Trypan blue exclusion test, as well
      as morphological, western blot and isobologram analyses were conducted. The
      results indicated that the combined ATRA and PKC412 treatment exhibited additive
      or synergistic effects in FLT3-mutated AML cell lines. These results provided in
      vitro evidence for the future clinical trials evaluating the effects of a
      combination treatment using PKC412 and ATRA on AML patients with FLT3-mutations.

PMID- 25592077
TI  - Local non-equilibrium thermodynamics.
AB  - Local Shannon entropy lies at the heart of modern thermodynamics, with much
      discussion of trajectory-dependent entropy production. When taken at both
      boundaries of a process in phase space, it reproduces the second law of
      thermodynamics over a finite time interval for small scale systems. However,
      given that entropy is an ensemble property, it has never been clear how one can
      assign such a quantity locally. Given such a fundamental omission in our
      knowledge, we construct a new ensemble composed of trajectories reaching an
      individual microstate, and show that locally defined entropy, information, and
      free energy are properties of the ensemble, or trajectory-independent true
      thermodynamic potentials. We find that the Boltzmann-Gibbs distribution and
      Landauer's principle can be generalized naturally as properties of the ensemble,
      and that trajectory-free state functions of the ensemble govern the exact
      mechanism of non-equilibrium relaxation. 

PMID- 25592078
TI  - Pathogenesis of fallopian tube damage caused by Chlamydia trachomatis infections.
AB  - Chlamydia trachomatis is the leading cause of bacterial sexually transmitted
      disease worldwide resulting in 4-5 million new cases of Chlamydia annually and an
      estimated 100 million cases per annum. Infections of the lower female genital
      tract (FGT) frequently are asymptomatic; thus, they often remain undiagnosed or
      untreated. If infections are either not resolved or left untreated, chlamydia can
      ascend to the upper FGT and infect the fallopian tubes (FTs) causing salpingitis
      that may lead to functional damage of the FTs and tubal factor infertility (TFI).
      Clinical observations and experimental data have indicated a role for antibodies
      against C. trachomatis proteins such as the 60-kDa heat shock protein 60 (cHSP60)
      in the immunopathogenesis of TFI. When released from infected cells, cHSP60 can
      induce proinflammatory immune responses that may functionally impair the FTs
      leading to fibrosis and luminal occlusion. Chlamydial pathogenesis of
      irreversible and permanent tubal damage is a consequence of innate and adaptive
      host immune responses to ongoing or repeated infections. The extracellular matrix
      that is regulated by metalloproteinases may also be modified by chlamydial
      infections of the FGT. This review will highlight protective and pathogenic
      immune responses to ongoing and repeated chlamydial infections of the FGT. It
      will also present two recent hypotheses to explain mechanisms that may contribute
      to FT damage during a C. trachomatis infection. If Chlamydia immunopathology can
      be controlled, it might yield a method of inducing fibrosis and thus provide a
      means of nonsurgical permanent contraception for women. 

PMID- 25592079
TI  - Benchmark pregnancy rates and the assessment of post-coital contraceptives: an
      update.
AB  - OBJECTIVE: In 2001, we provided benchmark estimates of probability of pregnancy
      given a single act of intercourse. Those calculations assumed that intercourse
      and ovulation are independent. Subsequent research has shown that this assumption
      is not valid. We provide here an update of previous benchmark estimates. STUDY
      DESIGN: We reanalyze earlier data from two North Carolina studies that collected
      daily urine samples and recorded daily intercourse for multiple menstrual cycles.
      One study comprised 68 sexually active women with either an intrauterine device
      or tubal ligation. The second was of 221 women who planned to become pregnant and
      had discontinued use of any birth control at enrollment. Participants had no
      known fertility problems. New statistical analyses were based on Monte Carlo
      simulations and Bayesian methods. RESULTS: The probability that a single act of
      intercourse occurs within a woman's fertile window is 25%, compared with 20% in
      previous calculations. The probability of pregnancy with intercourse on a given
      menstrual cycle day is correspondingly higher than previously estimated, with the
      largest increases occurring on menstrual days 12-22. These increases are,
      however, fairly small (for example, the peak chance of conception on menstrual
      day 13 increased from 8.6% to 9.7%). CONCLUSIONS: Previous benchmark rates of
      pregnancy with one act of intercourse were moderately underestimated due to a
      mistaken assumption about the independence of intercourse and ovulation.
      IMPLICATIONS STATEMENT: The chance of pregnancy with a single act of unprotected
      intercourse is greater than previously estimated. Previous benchmarks may
      underestimate the efficacy of post-coital contraception.

PMID- 25592080
TI  - Efficacy and safety of medical abortion using mifepristone and buccal misoprostol
      through 63 days.
AB  - OBJECTIVE: The aim of this study was to report on the safety and efficacy of an
      evidence-based medical abortion regimen utilizing 200 mg of mifepristone orally
      followed by home use of 800 mcg misoprostol buccally 24-48 h later through 63
      days estimated gestational age. STUDY DESIGN: We analyzed outcomes in women
      presenting for medical abortion between April 1, 2006, and May 31, 2011, using an
      evidence-based alternative to the United States Food and Drug Administration
      (FDA)-approved regimen. Cases were identified for this descriptive study from our
      electronic practice management (EPM) database, and our electronic database on
      adverse events was queried for information on efficacy and safety. The primary
      outcome was successful abortion. Logistic regression was used to identify
      predictors of successful abortion. RESULTS: Among the 13,373 women who completed
      follow-up, efficacy of the regimen was 97.7%. Efficacy was highest at 29 to 35
      days (98.8%) and 36 to 42 days (98.8%) of gestation and lowest at 57 to 63 days
      (95.5%). The odds of needing aspiration for any reason were greatest at higher
      gestational ages. Rates of infection requiring hospitalization and rates of
      transfusion were 0.01 and 0.03%, respectively. CONCLUSIONS: An evidence-based
      regimen of 200 mg of mifepristone orally followed by home use of 800 mcg of
      buccal misoprostol 24-48 h later is safe and effective through 63 days estimated
      gestational age. Further, the need for aspiration for any reason was low, and
      hospitalization was rare. IMPLICATIONS: This study reinforces the safety and
      efficacy of the evidence-based regimen for medical abortion (200 mg mifepristone
      orally followed by home use of 800 mcg of misoprostol buccally 24-48 h later)
      through 63 days estimated gestational age, and contributes to the existing
      evidence against restrictions requiring use of the FDA-approved regimen.

PMID- 25592081
TI  - The history and current status of fallopian tube pressures - developing alternate
      methods for confirmation of tubal occlusion.
AB  - Permanent contraception with hysteroscopic tubal ligation is an increasingly
      popular choice for women around the world. However, inconveniences associated
      with the required confirmation test for tubal occlusion can be prohibitive. As
      new methods of permanent contraception are being investigated, ways of making all
      aspects of the procedure more accessible and comfortable for women should be
      considered. Means of examining tubal patency in the infertility population, such
      as tubal perfusion pressures measured at the time of hysterosalpingogram (HSG),
      provide inspiration for alternative methods of tubal occlusion confirmation after
      contraception. Evaluation of intrauterine pressures measured by a manometer
      attached to an intrauterine balloon catheter could serve as a preliminary tool
      for verification of tubal occlusion; higher pressures would indicate tubal
      occlusion and lower pressures would indicate the need for confirmatory HSG. The
      development and validation of this technique is ongoing and could reduce overall
      costs and patient burdens associated with the current tubal occlusion
      confirmation procedure. 

PMID- 25592082
TI  - Effect of the ratios of unsaturated fatty acids on the expressions of genes
      related to fat and protein in the bovine mammary epithelial cells.
AB  - The objective of this study was to evaluate the effects of the different ratios
      of unsaturated fatty acids (UFAs) (oleic acid, linoleic acid, and linolenic acid)
      on the cell viability and triacylglycerol (TAG) content, as well as the mRNA
      expression of the genes related to lipid and protein synthesis in bovine mammary
      epithelial cells (BMECs). Primary cells were isolated from the mammary glands of
      Holstein dairy cows and were passaged twice. Afterward, the cells were randomly
      allocated to six treatments, five UFA-treated groups, and one control group. For
      all of the treatments, the the fetal bovine serum in the culture solution was
      replaced with fatty acid-free BSA (1 g/L), and the cells were treated with
      different ratios of oleic, linoleic, and linolenic acids (0.75:4:1, 1.5:10:1,
      2:13.3:1, 3:20:1, and 4:26.7:1) for 48 h, which were group 1 to group 5. The
      control culture solution contained only fatty acid-free BSA without UFAs (0 MUM).
      The results indicated that the cell viability was not affected by adding
      different ratios of UFAs, but the accumulation of TAG was significantly
      influenced by supplementing with different ratios of UFAs. Adding different
      ratios of UFAs suppressed the expression of ACACA and FASN but had the opposite
      effect on the abundances of FABP3 and CD36 mRNA. The expression levels of PPARG,
      SPEBF1, CSN1S1, and CSN3 mRNA in the BMECs were affected significantly after
      adding different ratios of UFAs. Our results suggested that groups 1, 2, and 3
      (0.75:4:1, 1.5:10:1, and 2:13.3:1) had stronger auxo-action on fat synthesis in
      the BMECs, where group 3 (2:13.3:1) was the best, followed by group 4 (3:20:1).
      However, group 5 (4:26.7:1) was the worst. Genes related to protein synthesis in
      the BMECs were better promoted in groups 2 and 3, and group 3 had the strongest
      auxo-action, whereas the present study only partly examined the regulation of
      protein synthesis at the transcriptional level; more studies on translation level
      are needed in the future. Therefore, when combining fat and protein synthesis,
      group 3 could be obviously fat and protein synthesis in the BMECs concurrently.
      However, further studies are necessary to elucidate the mechanism for regulating
      fat and protein synthesis in the BMECs.

PMID- 25592083
TI  - Derivation of embryonic stem cells from Kunming mice IVF blastocyst in feeder-
      and serum-free condition.
AB  - Kunming mice are widely used in China; however, it is difficult to isolate
      embryonic stem cells (ESCs) in conventional derivation condition containing
      feeder cells and serum. 6-Bromoindirubin-3'-oxime (BIO), a glycogen synthase
      kinase 3 (GSK3) inhibitor, could facilitate the maintenance of pluripotency of
      ESCs. Therefore, BIO could be considered as a candidate to replace feeder cells
      and serum. On the other hand, in vitro fertilization (IVF) is an important
      technology in assisted reproduction. It is reported that there was some
      difference in gene expression between IVF and in vivo developed blastocyst. ESCs
      derived from IVF blastocyst could provide a valuable tool to research the effect
      of IVF on differentiation and development. In the present study, we established
      two novel ESC lines from IVF blastocyst of Kunming mice in a feeder- and serum
      free condition containing 2.5 MUM BIO. In this condition, expanded IVF blastocyst
      could spontaneously hatch from zonae pellucidae and attached to the gelatin
      coated bottom of dishes. ESC-like outgrowth could be observed without overfull
      trophoblast cells. After further propagation, two Kunming mice ESC lines,
      designated as KMES1 and KMES2, were obtained. These two novel ESCs shared common
      morphological characteristics with other rodent ESCs, showed strong alkaline
      phosphatase activity, and expressed pluripotent markers, including Oct-4, Nanog,
      and SSEA-1. Embryoid body (EB) and teratoma test indicated that these ESCs could
      spontaneously differentiate into cells representative of all three embryonic germ
      layers. 

PMID- 25592084
TI  - Regulation of appetite, satiation, and body weight by enteroendocrine cells. Part
      2: therapeutic potential of enteroendocrine cells in the treatment of obesity.
AB  - Obesity is an epidemic and medical issue. Investigating the pathways regulating
      appetite, food intake, and body weight is crucial to find strategies for the
      prevention and treatment of obesity. In the context of therapeutic strategies, we
      focus here on the potential of enteroendocrine cells (EECs) and their secreted
      hormones in the regulation of body weight. We review the role of the
      enteroendocrine system during weight loss after lifestyle intervention or after
      bariatric surgery. We discuss the therapeutic potential of EECs and their
      hormones as targets for new treatment strategies. In fact, targeting nutrient
      receptors of EECs with a nutritional approach, pharmaceutical agents or
      prebiotics delivered to the lumen may provide a promising new approach.

PMID- 25592086
TI  - The PAP test and the pap smear.

PMID- 25592085
TI  - EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit
      rotator cuff repair.
AB  - BACKGROUND/AIMS: The rate of healing failure after surgical repair of chronic
      rotator cuff tears is considerably high. The aim of this study was to investigate
      the function of the zinc finger transcription factor early growth response 1
      (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon
      formation, healing, and tendon tear repair using an animal model of rotator cuff
      repair. METHODS: Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation
      as well as the expression of related genes were determined in EGR1-overexpressing
      TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining,
      quantitative PCR, and western blotting. A rabbit rotator cuff repair model was
      established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto
      repair sites. The rabbits were sacrificed 8 weeks after repair operation, and
      tissues were histologically evaluated and tenocyte-related gene expression was
      determined. RESULTS: EGR1 induced tenogenic differentiation of TSCs and inhibited
      non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in
      a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was
      involved in EGR1-induced tenogenic differentiation and rotator cuff tendon
      repair. CONCLUSION: EGR1 plays a key role in tendon formation, healing, and
      repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for
      rotator cuff tendon repair surgeries.

PMID- 25592087
TI  - Cervical cancer 2015 and beyond: a focus on innovative treatments and attention
      to survivorship.

PMID- 25592088
TI  - Exploring the therapeutic rationale for angiogenesis blockade in cervical cancer.
AB  - PURPOSE: This review highlights the molecular and pathologic evidence that
      cervical cancer is driven by angiogenesis and presents a summary of the recent
      clinical research in antiangiogenesis therapy for advanced cervical cancer with a
      focus on the use of bevacizumab. METHODS: The articles chosen for this review
      reveal the rationale for antiangiogenesis agents in cervical cancer from 3
      perspectives: pathologic, molecular, and clinical data. FINDINGS: Several
      translational investigations have revealed that proangiogenic signaling cascades
      are active in cervical carcinogenesis and can be used to improve patient outcomes
      in advanced disease. For example, in a recently published study of patients with
      recurrent and metastatic cervical cancer, bevacizumab was the first targeted
      agent to improve overall survival in a gynecologic cancer when successfully
      combined with 2 different chemotherapy regimens. IMPLICATIONS: Because of recent
      advances in screening, aggressive management of cervical intraepithelial
      neoplasia, and human papillomavirus vaccination, cervical cancer is preventable
      and curable with radical surgery plus lymphadenectomy surgery or chemoradiation
      plus brachytherapy if detected early. Unfortunately, for patients with metastatic
      or recurrent disease, effective therapeutic options are limited for this
      aggressive life-threatening condition. However, molecularly targeted agents have
      provided a critical opportunity to improve patient outcomes beyond optimizing
      cytotoxic chemotherapy regimens so that they may benefit from other agents or
      emergent therapies in the future.

PMID- 25592089
TI  - Immunotherapy: an evolving paradigm in the treatment of advanced cervical cancer.
AB  - PURPOSE: In 2014, the US Food and Drug Administration approved the first targeted
      agent, bevacizumab, in the treatment of advanced stage, persistent, or recurrent
      cervical cancer. This oncologic milestone has catalyzed interest in the
      investigation of alternate therapies, including immunotherapy, in an effort to
      extend life and possibly cure patients with advanced stage disease. METHODS: This
      review article focuses on the evolving paradigm of immunotherapy in the treatment
      of cervical cancer, describing the biologic basis of this treatment modality and
      discussing applicable Phase I to II clinical trials. FINDINGS: To date several
      trials have been conducted exploring vaccine-based therapies, adoptive T-cell
      therapy, and immune-modulating agents in patients with cervical cancer with
      promising results. IMPLICATIONS: Immunotherapy represents a promising therapeutic
      paradigm in the treatment of advanced cervical cancer. Additional investigation
      is warranted to try and identify alternate immune targets and predictors of
      response, allowing for the selection of patients most likely to benefit from
      immune-based treatments.

PMID- 25592090
TI  - Cervical cancer survivorship: long-term quality of life and social support.
AB  - PURPOSE: Surgery, radiotherapy, and chemotherapy are the mainstays of cervical
      cancer treatment. Many patients receive multiple treatment modalities, each with
      its own long-term effects. Given the high 5-year survival rate for cervical
      cancer patients, evaluation and improvement of long-term quality of life are
      essential. METHODS: Pertinent articles were identified through searches of PubMed
      for literature published from 1993 to 2014. We summarize quality of life data
      from long-term follow-up studies of cervical cancer patients. We additionally
      summarize small group interviews of Hispanic and non-Hispanic cervical cancer
      survivors regarding social support and coping. FINDINGS: Data are varied in terms
      of the long-term impact of treatment on quality of life, but consistent in
      suggesting that patients who receive radiotherapy as part of their treatment have
      the highest risk of increased long-term dysfunction of bladder and bowel, as well
      as sexual dysfunction and psychosocial consequences. Rigorous investigations
      regarding long-term consequences of treatment modalities are lacking.
      IMPLICATIONS: Continued work to improve treatment outcomes and survival should
      also include a focus on reducing adverse long-term side effects. Providing
      supportive care during treatment and evaluating the effects of supportive care
      can reduce the prevalence and magnitude of long-term sequelae of cervical cancer,
      which will in turn improve quality of life and quality of care.

PMID- 25592091
TI  - Impact of prolonged-release oxycodone/naloxone on outcomes affecting patients'
      daily functioning in comparison with extended-release tapentadol: a systematic
      review.
AB  - PURPOSE: The objective of this systematic review was to assess the clinical
      efficacy, safety, tolerability, and health-related quality of life outcomes
      associated with management of moderate-to-severe chronic pain with
      oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on
      patients' daily functioning. METHODS: Literature from a wide range of sources,
      including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register
      of Controlled Trials, was searched to identify randomized controlled trials
      investigating tapentadol or oxycodone/naloxone for the treatment of patients with
      chronic pain. A network meta-analysis was conducted to determine the relative
      efficacy and safety profiles of these treatments. FINDINGS: Oxycodone/naloxone
      was significantly better than tapentadol with respect to the Patient Assessment
      of Constipation Symptoms total score (risk ratio = -3.60; 95% credible interval, 
      5.36 to -2.11) and revealed a significantly lower risk of dizziness (risk ratio =
      0.72; 95% credible interval, 0.42-0.98). Oxycodone/naloxone was directionally
      favored, although not significantly superior to tapentadol for headache, fatigue,
      dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE
      outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all
      cause withdrawals from studies, tapentadol was directionally favored without any
      statistical difference from oxycodone/naloxone. However, the two treatments were
      not wholly comparable for the evaluation of pain efficacy because of differences
      in on-study rescue medication and a higher baseline pain severity in the
      tapentadol studies. IMPLICATIONS: Oxycodone/naloxone offers significant
      improvements in Patient Assessment of Constipation Symptoms total score and
      dizziness and was directionally favored for fatigue and headache compared with
      extended-release tapentadol, which may translate to improved patient daily
      functioning and health-related quality of life.

PMID- 25592092
TI  - The oxidative potential of differently charged silver and gold nanoparticles on
      three human lung epithelial cell types.
AB  - BACKGROUND: Nanoparticle (NPs) functionalization has been shown to affect their
      cellular toxicity. To study this, differently functionalized silver (Ag) and gold
      (Au) NPs were synthesised, characterised and tested using lung epithelial cell
      systems. METHODS: Monodispersed Ag and Au NPs with a size range of 7 to 10 nm
      were coated with either sodium citrate or chitosan resulting in surface charges
      from -50 mV to +70 mV. NP-induced cytotoxicity and oxidative stress were
      determined using A549 cells, BEAS-2B cells and primary lung epithelial cells
      (NHBE cells). TEER measurements and immunofluorescence staining of tight
      junctions were performed to test the growth characteristics of the cells.
      Cytotoxicity was measured by means of the CellTiter-Blue (r) and the lactate
      dehydrogenase assay and cellular and cell-free reactive oxygen species (ROS)
      production was measured using the DCFH-DA assay. RESULTS: Different growth
      characteristics were shown in the three cell types used. A549 cells grew into a
      confluent mono-layer, BEAS-2B cells grew into a multilayer and NHBE cells did not
      form a confluent layer. A549 cells were least susceptible towards NPs,
      irrespective of the NP functionalization. Cytotoxicity in BEAS-2B cells increased
      when exposed to high positive charged (+65-75 mV) Au NPs. The greatest
      cytotoxicity was observed in NHBE cells, where both Ag and Au NPs with a charge
      above +40 mV induced cytotoxicity. ROS production was most prominent in A549
      cells where Au NPs (+65-75 mV) induced the highest amount of ROS. In addition,
      cell-free ROS measurements showed a significant increase in ROS production with
      an increase in chitosan coating. CONCLUSIONS: Chitosan functionalization of NPs,
      with resultant high surface charges plays an important role in NP-toxicity. Au
      NPs, which have been shown to be inert and often non-cytotoxic, can become toxic
      upon coating with certain charged molecules. Notably, these effects are dependent
      on the core material of the particle, the cell type used for testing and the
      growth characteristics of these cell culture model systems.

PMID- 25592093
TI  - Cardiovascular autonomic neuropathy in rheumatoid arthritis assessed by
      cardiovascular autonomic function tests: A cross-sectional survey.
AB  - OBJECTIVE: In this study, we aimed to evaluate cardiovascular autonomic
      neuropathy (CAN) in RA patients by cardiovascular autonomic function tests.
      Because CAN was reported of patients with automimmune rheumatic diseases those
      may in sudden death or myocardial infarction. METHODS: A total of 44 patients
      with RA and 44 age- and sex-matched healthy volunteers participated in this cross
      sectional study. Assessment of CAN was performed using cardiovascular reflex
      tests. These five tests were: 1) beat-to-beat heart rate variation during deep
      breathing; 2) heart rate response to standing up; 3) heart rate response to the
      Valsalva maneuver; 4) blood pressure response to standing up; and 5) blood
      pressure response to sustained handgrip. RESULTS: The mean age was 43.15 (SD,
      12.18) years (range, 23-68 years) in the RA group, and 38 were women. In beat-to
      beat heart rate variation during deep breathing, expiration-to-inspiration ratio
      was abnormal in 3 cases with RA (6.8%) but in 1 (2.3%) control subject (p=0.3),
      and maximum minus minimum heart rate was abnormal in 8 patients (18.2%) and in 3
      (6.8%) control subjects (p=0.1). 2) In heart rate response to standing up, all
      patients and controls had normal results. Valsalva ratio was abnormal in 7 RA
      patients (15.9%) and in 7 control subjects (15.9%). Blood pressure response to
      standing up was normal in RA patients but abnormal in 1 (2.3%) control subject
      (p=0.4). Blood pressure response to sustained handgrip was abnormal in 5 RA
      patients (11.4%) and 2 (4.6%) control subjects (p=0.2). CONCLUSION: Our study
      failed to show any statistically significant difference between cardiovascular
      autonomic function tests in RA patients with control subjects by our test done.

PMID- 25592094
TI  - The effects of baseline heart rate recovery normality and exercise training
      protocol on heart rate recovery in patients with heart failure.
AB  - OBJECTIVE: It is unclear which exercise training protocol yields superior heart
      rate recovery (HRR) improvement in heart failure (HF) patients. Whether baseline
      HRR normality plays a role in the improvement is unknown. We hypothesized that an
      exercise training protocol and baseline HRR normality would be factors in
      altering HRR in HF patients. METHODS: In this prospective, randomized, controlled
      and 3 group parallel study, 41 stable HF patients were randomly assigned to 3
      times-weekly training sessions for 12 weeks, consisting of i) 30 minutes of
      interval training (IT) (n=17, 63.7+/-8.8 years old) versus ii) 30 minutes of
      continuous training (CT) (n=13, 59.6+/-6.8 years old) versus iii) no training
      (CON) (n=11, 60.6+/-9.9 years old). Each patient had cardiopulmonary exercise
      testing before and after the training program. Maximum heart rates attained
      during the test and heart rates at 1 and 2 min (HRR1 and HRR2) during the
      recovery phase were recorded. Paired samples t-test or Wilcoxon signed-rank test
      was used for comparisons before and after training. One-way ANOVA or Kruskal
      Wallis variance analysis was used for comparisons among groups. RESULTS: HRR1 was
      unchanged after training. HRR2 improved in the IT group after training, and post
      training HRR2 values were significantly faster in the IT group than in controls.
      Both HRR1 and HRR2 was significantly faster, irrespective of exercise protocol in
      patients with abnormal baseline values after training. CONCLUSION: HRR1 did not
      improve after training. HRR2 improved only in the IT group. Both HRRs in patients
      with abnormal baseline values improved after both exercise protocols. IT might be
      superior to CT in improving HRR2. Baseline HRR might play a role in its response
      to exercise.

PMID- 25592095
TI  - Association between oxidative stress index and post-CPR early mortality in
      cardiac arrest patients: A prospective observational study.
AB  - OBJECTIVE: Cardiopulmonary resuscitation (CPR) is a series of lifesaving actions
      that improve the chance of survival following cardiac arrest (CA). Many clinical
      and laboratory parameters, such as the presence of asystole, out-of-hospital CPR,
      and duration of cardiac arrest, are associated with failed CPR in patients with
      CA. Asystole is a state of no cardiac electrical activity, along with the absence
      of contractions of the myocardium and absence of cardiac output. Oxidative stress
      index (OSI), which is the ratio of total oxidative status to total antioxidant
      status, increases by ischemia-reperfusion injury. We investigated whether OSI
      levels in patients with CA could predict early mortality after CPR. METHODS: This
      study has a prospective observational cohort design. Five patients with a history
      of cancer, four patients who developed hemolysis in their blood, six patients who
      were transferred to our hospital from other hospitals, and six patients in whom
      blood samples for OSI could not be stored properly were excluded. Finally, a
      total of 90 in-hospital or out-of-hospital CA patients and 40 age- and sex
      matched healthy volunteers as the control group were evaluated prospectively. The
      patients were classified according to the CPR response into a successful group
      (n=46) and a failed group (n=44). Comparisons between groups were performed using
      one-way ANOVA with post hoc analysis by Tukey's HSD or independent samples t-test
      and the Kruskal-Wallis tests or Mann- Whitney U test for normally and abnormally
      distributed data, respectively. Also, we used chi-square test, Spearman's
      correlation test, univariate and multible logistic regression analyses, and
      receiver operator characteristic curve analysis. RESULTS: OSI was 3.0+/-4.0,
      5.6+/-4.3, and 8.7+/-3.8 in the control group, the successful CPR group, and the
      failed CPR group, respectively (p<0.001 for the 2 comparisons). OSI on admission,
      ischemia-modified albumin, presence of asystole, mean duration of cardiac arrest,
      out-of-hospital CPR, pH, and potassium and sodium levels were found to have
      prognostic significance in the univariate analysis. In the multivariate logistic
      regression model, OSI on admission (OR=1.325, p=0.003), ischemia-modified albumin
      (OR=1.008, p=0.005), presence of asystole (OR=13.576, p<0.001), and sodium level
      (OR=1.132, p=0.029) remained associated with an increased risk of early
      mortality. In addition, the optimal cut-off value of OSI to predict post-CPR
      mortality was measured as >6.02, with 84.1% sensitivity and 76.1% specificity.
      CONCLUSION: Elevated OSI levels can predict failed CPR in CA patients.

PMID- 25592096
TI  - Lower serum 25-hydroxyvitamin D level is associated with impaired myocardial
      performance and left ventricle hypertrophy in newly diagnosed hypertensive
      patients.
AB  - OBJECTIVE: Vitamin D deficiency is an independent risk factor for cardiovascular
      mortality. The relationship between vitamin D level and left ventricle (LV)
      myocardial performance index (MPI=Tei index), which incorporates both LV systolic
      function and diastolic function, was not investigated in previous studies. We
      hypothesized that vitamin D level may be associated with LV function and
      geometry. We aimed to investigate the association between serum 25-hydroxyvitamin
      D (25 [OH] D) levels and MPI and LV hypertrophy in hypertensive patients with
      newly diagnosed and preserved ejection fraction. METHODS: We studied 151
      sequential newly diagnosed hypertensive subjects who lived in the Cukurova region
      without known cardiovascular risk factors or overt heart disease (mean age:
      62.8+/-10.4 years). Serum 25 (OH) D was measured using a direct competitive
      chemiluminescent immunoassay. The patients were divided into two groups according
      to serum 25 (OH) D level: vitamin D-non-deficient group (vitamin D>= 20.00 ng/mL,
      n=53) and vitamin D-deficient group (vitamin D< 20.00 ng/mL, n=98). MPI was
      defined as the sum of isovolumic contraction and relaxation times divided by the
      ejection time. LV mass index (LVMI) was calculated by using the Devereux formula
      and body surface area. RESULTS: MPI and LVMI values were lower and low-density
      lipoprotein (LDL) levels were higher in patients who were vitamin D-non-deficient
      than patients who were vitamin D-deficient (p<0.05 for all). Multivariate linear
      regression analysis showed that serum 25 (OH) D was independently associated with
      MPI (beta=-0.426, p<0.001), LVMI (beta=-0.345, p=<0.001), and LDL (beta=0.140,
      p<0.026). CONCLUSION: Lower serum 25 (OH) D levels are significantly associated
      with impaired myocardial performance and LVMI.

PMID- 25592097
TI  - Mean platelet volume is associated with aortic intima-media thickness in patients
      without clinical manifestation of atherosclerotic cardiovascular disease.
AB  - OBJECTIVE: Mean platelet volume (MPV) plays a pivotal role in the pathophysiology
      of atherosclerotic disease. Thoracic aortic intima-media thickness (IMT) was
      reported as an earlier marker of preclinical atherosclerosis than carotid IMT.
      However, the relationship between MPV and aortic IMT was not investigated. We
      aimed to assess the relationship between thoracic aortic IMT and MPV in patients
      undergoing transesophageal echocardiography (TEE) examination for different
      indications. METHODS: We studied 190 patients (mean age 37.0+/-12.5 years) who
      underwent TEE for different indications. The patients who have known
      atherosclerotic disease were excluded from study. The patients were divided into
      2 groups according to the median thoracic aortic IMT values (IMTlow group <=13 mm
      and IMThigh group >13 mm). Platelet count and MPV were analyzed with an automated
      hematology analyzer. A multiple stepwise linear regression analysis was performed
      to identify the independent associations of thoracic aortic IMT. RESULTS: The
      highest MPV values were observed in the IMThigh group compared with the IMTlow
      group (9.5+/-10 fL vs. 10.9+/-1.2 fL, p<0.001). Also, the IMThigh group had
      higher age, hs-CRP, and uric acid levels (p<0.05 for all). Multiple linear
      regression analysis showed that aortic IMT was independently related with age
      (beta=0.340, p<0.001), uric acid (beta=0.111, p=0.041), hs-CRP (beta=0.200,
      p<0.001), and MPV (beta=0.482, p<0.001). CONCLUSION: MPV is independently related
      to the extent of subclinical thoracic aortic atherosclerosis. Increases in MPV
      may be a crucial biochemical marker for initial atherosclerosis.

PMID- 25592098
TI  - Rheumatoid factor mediates excess serum lipoprotein(a) for independent
      association with type 2 diabetes in men.
AB  - OBJECTIVE: The potential association of rheumatoid factor (RF) and lipoprotein
      (Lp)(a) levels, as well as with the likelihood of type 2 diabetes and
      hypertension, needs exploring. METHODS: Cross-sectional associations were sought
      in this unselected and population-based 1539-adult cohort (age 58.8+/-10.6
      years). RF was assayed nephelometrically. Multiple logistic regression analyses
      were used for covariates of RF positivity and for the latter's association with
      diabetes and hypertension. RESULTS: RF-positive individuals were older, fewer
      current smokers, had significantly lower fasting triglycerides (by 13%), higher
      fibrinogen, and tended to higher sex hormone-binding globulin (SHBG) levels.
      Whereas, women had a similar risk profile irrespective of RF status, RF-positive
      men had significantly higher Lp(a). In contrast to Lp(a) being positively
      correlated with SHBG in RF-negative subjects (r=0.08; p=0.007), an inverse
      correlation existed in seropositive individuals (r=-0.32, p=0.011), suggesting
      the interplay of an immune complex. In regression analyses, RF positivity was
      associated with Lp(a) in men but not in women, [OR 1.53 (1.19; 1.96)],
      independent of age, SHBG, and C-reactive protein (CRP). RF positivity was further
      associated with diabetes [OR 1.98 (95% CI 1.11; 3.52)] in the whole sample,
      additively to waist circumference and CRP, major determinants of diabetes. RF
      positive subjects were not significantly associated independently with
      hypertension. CONCLUSION: Autoimmune activation linked to Lp(a) is mediated by
      the autoantibody RF in contributing to the development of type 2 diabetes.

PMID- 25592099
TI  - Relationship between extent and complexity of coronary artery disease and
      different left ventricular geometric patterns in patients with coronary artery
      disease and hypertension.
AB  - OBJECTIVE: The relationship between severity of coronary artery disease (CAD) and
      left ventricler (LV) hypertrophy in hypertensive patients is well known. However,
      the association between the extent and complexity of CAD assessed with SYNTAX
      score (SS) and different LV geometric patterns has not been investigated. We
      aimed to investigate the association between SYNTAX score and different LV
      geometric patterns in hypertensive patients. METHODS: The study had been made in
      our clinic between January 2013 and August 2013. We studied 251 CAD patients who
      had hypertension and who underwent coronary angiography (147 males, 104 females;
      mean age 61.61+/-9.9 years). Coronary angiography was performed based on clinical
      indications. SS was determined in all patients. Echocardiographic examination was
      performed in all subjects. Four different geometric patterns were determined in
      patients according to LV mass index (LVMI) and relative wall thickness (RWT)
      (Groups: NG- normal geometry, CR- concentric remodeling, EH- eccentric
      hypertrophy, and CH- concentric hypertrophy). Biochemical markers were measured
      in all participants. RESULTS: The highest SS values were observed in the CH group
      compared with the NG, CR, and EH groups (p<0.05 for all). Also, the SS values of
      the EH group were higher than in the NG and CR groups (p<0.05 for all).
      Multivariate linear regression analysis showed that SS was independently
      associated with LV geometry (beta=0.316, p=0.001), as well as age (beta=0.163,
      p=0.007) and diabetes (beta=-0.134, p=0.022). CONCLUSION: SYNTAX score is
      independently related with LV geometry in hypertensive patients. This result
      shows that LV remodeling is parallel to the increase in the extent and complexity
      of CAD in our study patients.

PMID- 25592100
TI  - The relation between intensity and complexity of coronary artery lesion and
      oxidative stress in patients with acute coronary syndrome.
AB  - OBJECTIVE: Oxidative stress plays a major role in the development of
      atherosclerosis. However, the relationship between oxidative stress and
      complexity and intensity of coronary artery disease is less clear. The aim of
      this study is to assess the relationship between oxidative stress markers and the
      complexity and intensity of coronary artery disease in patients with acute
      coronary syndrome (ACS). METHODS: Sixty-seven consecutive patients with an early
      phase of ACS (<3 h) were included in this single-centre, cross-sectional,
      prospective study. Syntax and Gensini scores were calculated based on
      angiographic findings. Patients were divided into two CAD complexity groups
      according to their Syntax scores: low SYNTAX score (<22) and moderate to high
      SYNTAX score (>=22). Likewise patients were divided into two CAD severity groups
      according to the median Gensini score of 64: less intensive CAD with Gensini
      score (<64) and intensive CAD with Gensini score >=64. Blood samples were taken
      in 1 hour within administration in order to measure total oxidative status (TOS)
      and total antioxidant capacity (TAC) levels determined by Erel method. Oxidative
      stress index (OSI) was calculated by TOS /TAC. RESULTS: There was no significant
      difference between the two SYNTAX groups for oxidative stress markers. Median TOS
      and OSI values were significantly high in the intensive CAD group (p=0.005,
      p=0.04, respectively). The Gensini score was positively correlated with TOS and
      OSI (p=0.003, p=0.02, respectively). CONCLUSION: Oxidative stress markers may be
      considered supportive laboratory parameters related to CAD intensity but not
      complexity in ACS patients.

PMID- 25592101
TI  - Comparison of the GRACE risk score and the TIMI risk index in predicting the
      extent and severity of coronary artery disease in patients with acute coronary
      syndrome.
AB  - OBJECTIVE: The prognostic value of the Global Registry of Acute Coronary Events
      (GRACE) risk score (GRS) and the Thrombolysis In Myocardial Infarction (TIMI)
      risk index (TRI) has been reported in coronary artery disease (CAD) patients. We
      aimed to evaluate the relationship between the GRS, TRI, and severity of CAD
      evaluated by SYNTAX score (SS) in patients with acute coronary syndrome (ACS).
      METHODS: Patients with ACS who were admitted to the coronary care unit of our
      institution were retrospectively evaluated in this study. A total of 287 patients
      with ACS [154 non-ST elevated ACS (NSTE-ACS), 133 ST elevated myocardial
      infarction (STEMI)] were included in the study. The GRS and TRI were calculated
      on admission using specified variables. The severity of CAD was evaluated using
      the SS. The patients were divided into low (GRS<109)-, intermediate (GRS 109-140)
      , and high (GRS>140)-risk groups and group 1 (TRI<17), group 2 (TRI 17-26), and
      group 3 (TRI>26) according to GRS and TRI scores. A Pearson correlation analysis
      was used for the relation between GRS, TRI, and SS. RESULTS: Patients with a
      history of coronary artery bypass surgery, those who had missing data for
      calculating the GRS and TRI, and those whose systolic blood pressure (SBP) was
      more than 180 mm Hg or whose diastolic blood pressure (DBP) was more than 110 mm
      Hg were excluded from the study. Were excluded from the study. There were
      significant differences in mean age (p<0.001), heart rate (p<0.001), SS
      (p<0.001), TRI (p<0.001), rate of NSTE-ACS (p<0.001), and STEMI (p<0.001) in all
      patients between the risk groups. There was a positive significant correlation
      between the GRS and the SS (r=0.427, p<0.001), but there were no significant
      correlation between the TRI and SS (r=0.121, p=0.135). The area under the ROC
      curve value for GRS was 0.65 (95% CI: 0.56-0.74, p=0.001) in the prediction of
      severity of CAD. CONCLUSION: The GRS is more associated with SS than TRI in
      predicting the severity of CAD in patients with ACS.

PMID- 25592102
TI  - Is the neutrophil-to-lymphocyte ratio indicative of inflammatory state in
      patients with obesity and metabolic syndrome?
AB  - OBJECTIVE: Obesity causes subclinical inflammation. Leukocyte count and high
      sensitivity C-reactive protein (hs-CRP) are used to indicate inflammation in
      clinical practice. Also, inflammatory markers are evaluated as important
      indicators of cardiovascular risk in patients with obesity and metabolic syndrome
      (MetS). We aimed to investigate the usage of the neutrophil-lymphocyte ratio
      (NLR) as an inflammatory marker in obese patients with and without MetS. METHODS:
      The study included a total of 1267 patients. The patients were assigned groups
      according to degree of obesity and status of MetS. Metabolic and inflammatory
      markers were compared between groups, and correlation analysis was performed.
      RESULTS: Leukocyte count and hs-CRP were significantly different (p<0.001), but
      NLR was not different between body mass index (BMI) groups (p=0.168). Both
      lymphocyte and neutrophil counts were significantly increased with increased
      degree of obesity (p<0.001, p=0.028, respectively). Leukocyte, neutrophil, and
      lymphocyte counts and hs-CRP level showed a significant correlation with BMI
      (r=0.198, p<0.001; r=0.163, p<0.001; r=0.167, p<0.001; r=0.445, p<0.001,
      respectively), whereas NLR was not correlated with BMI (r=0.017, p=0.737). Only a
      significant association between a MetS severity of 5 and 4 with hs-CRP level was
      observed (p=0.028), whereas there was no statistically significant association
      for leukocyte count and NLR (p=0.246; p=0.643, respectively). CONCLUSION: NLR was
      not a good indicator of inflammation, while leukocyte and hs-CRP were more useful
      biomarkers to indicate inflammation in non-diabetic patients with obesity and
      MetS.

PMID- 25592103
TI  - A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new
      potential mechanism in the progression of atherosclerosis and diabetes.
AB  - OBJECTIVE: Coronary artery disease is characterized by atherosclerosis in the
      vessel wall. Recently, it has been thought that increasing LDL-binding capacity
      of subendothelial proteoglycan fragments that are formed by protease activity can
      be responsible for the initiation of atherosclerosis. ADAMTS4 is a member of the
      versican-degrading proteinases. In vitro studies demonstrated that TGFb inhibits
      the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate
      the role and association between TGFb1 and ADAMTS4 in coronary artery disease.
      METHODS: A total of 84 cases with atheroma plaque and 72 controls without plaque
      were analyzed. The severity of disease was determined by Gensini score. TGFb1
      gene polymorphisms were genotyped by the PCR-RFLP method. TGFb1 and ADAMTS4 serum
      levels were measured by ELISA method. Statistical analyses of genotypes and their
      relationship with serum levels were performed by chi-square, student t test and
      ANOVA. RESULTS: ADAMTS4 levels were higher in cases compared with controls
      (p<0.05). In the patient group, ADAMTS4 levels were higher than in controls and
      correlated with TGFb1 serum levels (r=0.29; p<0.05) and severity of disease
      (r=0.20; p<0.05). The TGFb1 gene CCA haplotype was associated with 3.3-fold
      increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05).
      Unexpectedly, ADAMTS4 serum levels were also higher in diabetic cases (p=0.05).
      CONCLUSION: This study has demonstrated that ADAMTS4 may be responsible for the
      pathogenesis of atherosclerosis. This is the first report about the association
      between ADAMTS4 and TGFb1 serum levels in the progression of atherosclerosis in
      CAD. Furthermore, it is seen that TGFb1 haplotype can cause a genetic
      susceptibility to CAD in the Turkish population. To our knowledge, this is also
      the first report suggesting higher serum ADAMTS4 levels in diabetic patients.

PMID- 25592104
TI  - Comparison of floating wire and single wire techniques in right coronary ostial
      lesions in terms of procedural features and one-year clinical follow-up results.
AB  - OBJECTIVE: The floating wire technique is a special technique for solving
      interventional problems in aorta- ostial lesions. There are no long-term data in
      the literature for the floating wire technique in right aorto-ostial lesions.
      METHODS: One hundred twenty six patients were retrospectively analyzed in this
      study. All of these patients had a critical right coronary aorto-ostial lesion.
      The floating wire technique was performed on 64 patients, and the single wire
      technique was performed on 62 patients. The two groups were compared with each
      other in terms of lesional and procedural properties. Additionally, 1-year
      clinical follow-up results were compared between the two groups. RESULTS: There
      was no significant difference in terms of lesion properties between the groups.
      In the floating wire group, mean stent length, number of stents, mean procedure
      time, mean contrast volume, and mean fluoroscopy time were significantly lower
      than in the single wire group. At 1 year, 1 patient from each group had
      myocardial infarction, and no mortality was observed. In the floating wire group,
      the number of patients who experienced angina and the target lesion
      revascularization rate were both significantly lower than in the single wire
      group. CONCLUSION: The floating wire technique in right coronary ostial lesions
      provides a significant advantage over the single wire technique according to
      procedural and clinical follow-up results.

PMID- 25592105
TI  - Nonthyroidal illness syndrome in off-pump coronary artery bypass surger.
AB  - OBJECTIVE: It is well known that coronary artery bypass grafting (CABG) is often
      the cause of non-thyroidal illness syndrome (NTIS). Non-thyroidal illness
      syndrome (NTIS) is a state characterized by low levels of tri-iodo-thyronine (T3)
      and high levels of reverse T3 (rT3), with normal or low levels of thyroxin (T4)
      and normal, low-normal, or low levels of thyroid-stimulating hormone (TSH).
      Today, there are two main techniques of CABG: CABG with the use of
      cardiopulmonary bypass (on-pump coronary artery bypass - ONCAB) and CABG without
      the use of cardiopulmonary bypass (off-pump coronary artery bypass OPCAB), or
      'beating-heart surgery.' The OPCAB technique is considered to be less invasive.
      We prospectively investigated the influence of these surgical techniques on the
      occurrence of NTIS. METHODS: Serum levels of free fractions of thyroid hormones
      (FT3 and FT4) and TSH were analyzed in 70 consecutive patients subjected to CABG
      surgery, using the ONCAB technique in 36 patients and OPCAB technique in 34
      patients. The measurements of hormone levels were performed prior to surgery and
      12 hours and 14 days after surgery. RESULTS: The basic, the early, and the late
      postoperative serum levels of FT3 (p=0.458, p=0.632, p=0.869, respectively), FT4
      (p=0.664, p=0.301, p=0.417, respectively), and TSH (p=0.249, p=0.058, p=0.324,
      respectively) were similar in both groups. The levels of FT3 and TSH were
      significantly lower 12 hours after surgery (p<0.0001, p<0.0001, respectively),
      and the FT4 levels rose at the same time (p<0.0001). The third measurement showed
      the return of all investigated parameters back to physiological levels, although
      they were still not precisely within the initial values. CONCLUSION: NTIS occurs
      significantly in patients subjected to CABG. Although the OPCAB technique is
      considered to be less invasive, its impact on the occurrence of NTIS does not
      differ significantly from the ONCAB technique.

PMID- 25592106
TI  - Association of the rs10757274 SNP with coronary artery disease in a small group
      of a Pakistani population.
AB  - OBJECTIVE: The present study aimed to investigate the association between the
      rs10757274 SNP (present on locus 9p21 in the gene for CDKN2B-AS1) and coronary
      artery disease (CAD) in a local population of Pakistan. METHODS: It was a case
      control study. An allele-specific PCR-based strategy was used for the
      identification of genotypes. A total of 350 samples were used for the
      investigation, out of which 220 samples were CAD patients and 130 samples were
      normal healthy individuals. Effects of parameters, like family history of CAD,
      smoking, presence of diabetes, and hypertension, in changing the chances of CAD
      were studied. Odds ratio was estimated with 95% confidence interval. RESULTS: A
      strong association was observed between CAD and factors, like smoking (OR: 1.666;
      95% CI: 1.042-2.664), presence of hypertension (OR: 26.55; 95% CI: 15.95-44.20),
      diabetes (OR: 3.009; 95% CI: 1.841-4.920), and family history of CAD (OR: 4.9;
      95% CI: 2.965-8.099). Results for the association between the genotype on the
      basis of rs10757274 showed a strong association between the GG genotype and the
      occurrence of CAD (OR: 9.603; 95% CI: 5.746-16.05). CONCLUSION: The present
      results suggest the importance of the 9p21 locus in modulating the chances of
      CAD.

PMID- 25592107
TI  - The assessment of the relationship between variations in the apelin gene and
      coronary artery disease in Turkish population.
AB  - OBJECTIVE: Apelin is a novel endogenous peptide with inotropic and vasodilatory
      properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor.
      The aim of the study was to investigate the association of 2 single-nucleotide
      polymorphisms (SNPs) in the apelin gene with susceptibility to coronary artery
      disease (CAD) in the Turkish population. METHODS: The present observational case
      control study consisted of 244 subjects (134 angiographically proven CAD patients
      and 110 healthy controls) aged 30-65 years. The association of 2 SNPs (rs3115758
      and rs3115759) in the apelin gene and CAD risk was investigated. Real-time
      polymerase chain reaction (RT-PCR) was used to analyze the 2 SNPs in both the CAD
      and the healthy subjects. Allele and genotype frequencies between patients and
      control groups were compared using the Chi-square (chi2) test. The relationships
      of the 2 polymorphisms with the presence of CAD were determined with multiple
      binary logistic regression analysis after adjustment for CAD risk factors.
      RESULTS: TT and AA risk genotypes of the rs3115758 and rs3115759 variants in the
      apelin gene were found to be significantly related with the risk of CAD with the
      same power (OR: 6.36, 95% CI: 1.41-28.6) (p=0.007). After adjustments for
      traditional CAD risk factors, the homozygous TT genotype for rs3115758 and AA
      genotype for rs3115759 increased the CAD risk, both with an OR of 5.91.
      CONCLUSION: Genetic variants in the apelin gene are significantly associated with
      the risk of CAD in the Turkish population.

PMID- 25592108
TI  - Comparison of image quality and radiation dose between prospectively ECG
      triggered and retrospectively ECG-gated CT angiography: Establishing heart rate
      cut-off values in first-generation dual-source CT.
AB  - OBJECTIVE: To evaluate radiation dose and image quality of prospectively
      electrocardiography (ECG)-triggered and retrospectively ECG-gated coronary
      computed tomography (CT) angiography and to establish cut-off values of heart
      rates (HRs) for each technique in first-generation dual-source CT. METHODS: A
      total of 200 consecutive patients with suspected coronary artery disease were
      accepted into the study. Patients were selected randomly for each technique
      (prospective triggering group n=99, mean age 55.85+/-10.74 and retrospective
      gating group n=101, mean age 53.38+/-11.58). Two independent radiologists scored
      coronary artery segments for image quality using a 5-point scale. Also,
      attenuation values of each coronary artery segment and dose-length product values
      were measured. For each technique, cut-off HR values were determined for the best
      image quality. RESULTS: Mean image quality scores and attenuation values were
      found to be higher in the prospective triggering group (p<0.05). Mean radiation
      dose was 73% lower for the prospective triggering group (p<0.01). The cut-off HR
      values for good image quality scores were <=67 beats per minute (bpm) and <=80
      bpm for the prospective triggering and retrospective gating groups, respectively
      (p<0.05). Increased HR (>=68 and >=81 bpm, respectively) had negative effects on
      image quality (p<0.05). CONCLUSION: The prospective ECG triggering technique has
      better image quality scores than retrospective ECG gating, particularly in
      patients who have an HR of less than 68 bpm. Also, a 73% radiation dose reduction
      can be achieved with prospective ECG triggering. In patients with higher heart
      rates, retrospective ECG gating is recommended.

PMID- 25592109
TI  - Ambulatory arterial stiffness index is associated with impaired left atrial
      mechanical functions in hypertensive diabetic patients: A speckle tracking study.
AB  - OBJECTIVE: The ambulatory arterial stiffness index has been proposed as an
      indicator of arterial stiffness. The aim of this study was to test the hypothesis
      that increased ambulatory arterial stiffness index might be related with impaired
      left atrial function in hypertensive diabetic patients with no previous history
      of cardiovascular disease. METHODS: Inclusion criteria included office systolic
      BP> 130 mm Hg or diastolic BP> 80 mm Hg and absence of secondary causes of HT,
      whereas exclusion criteria LV ejection fraction <50%, history of significant
      coronary artery disease, chronic renal failure, atrial fibrillation/ flutter,
      second or third-degree atrioventricular block, moderate to severe valvular heart
      disease, history of cerebrovascular disease, non-dipper hypertensive pattern and
      sleep apnea. The study was composed of 121 hypertensive diabetic patients. Twenty
      four-hour ambulatory blood pressure monitoring and echocardiography were
      performed in each patient. The relationship between ambulatory arterial stiffness
      index and left atrial functions was analyzed. AASI was calculated as 1 minus the
      regression slope of diastolic BP plotted against systolic BP obtained through
      individual 24-h ABPM. RESULTS: The univariate analysis showed that ambulatory
      arterial stiffness index was positively correlated with age (r=:0.287, p=:0.001),
      hypertension duration (r=:0.388, p<0.001), fasting plasma glucose (r=:0.224,
      p=:0.014), HbA1c (r=:0.206, p=:0.023), LDL cholesterol (r=:0.254, p=:0.005), and
      also overall pulse pressure (r=:0.195, p=:0.002), office- pulse pressure
      (r=:0.188, p=:0.039), carotid intima-media thickness (r=:0.198, p=:0.029), E/E'
      (r=:0.248, p=:0.006), and left atrial volume index (r=:0.237, p=:0.009).
      Moreover, ambulatory arterial stiffness index was negatively correlated with eGFR
      (r=:(-) 0.242, p=:0.008), peak left atrial strain during ventricular systole [S
      LAs (r=:(-) 0.654, p<0.001)], peak left atrial strain at early diastole [S-LAe
      (r=:(-)0.215, p=:0.018)], and peak left atrial strain rate during ventricular
      systole [SR-LAs (r=:(-) 0.607, p<0.001)]. The multiple linear regression analysis
      showed that ambulatory arterial stiffness index was independently associated with
      peak left atrial strain rate during ventricular systole (SR-LAs) (p<0.001).
      CONCLUSION: In hypertensive diabetic patients, increased ambulatory arterial
      stiffness index is associated with impaired left atrial functions, independent of
      left ventricular diastolic dysfunction.

PMID- 25592110
TI  - Recombinant hirudin suppresses the viability, adhesion, migration and invasion of
      Hep-2 human laryngeal cancer cells.
AB  - Recombinant hirudin (rH) is a highly potent and specific inhibitor of thrombin,
      and has been shown to inhibit the growth and metastasis of several types of
      cancers in experimental tumor models. The objective of this study was to evaluate
      the antitumor effects and explore the underlying mechanisms of rH in Hep-2 human
      laryngeal carcinoma (LC) cells. Hep-2 cells were treated with various
      concentrations of rH for 24 h. The cell viability was evaluated by a water
      soluble tetrazolium salt (WST) assay. The adhesion ability of the cells was
      evaluated by cell adhesion to fibronectin. Cell migration and invasion were
      measured with the Boyden chamber assay. Cell apoptosis was detected by Hoechst
      33324 fluorescence staining. A chicken chorioallantoic membrane (CAM) assay was
      used to assess the effects of rH on angiogenesis in vivo. Western blotting was
      used to detect the expression levels of vascular endothelial growth factor
      receptor (VEGF-R), focal adhesion kinase (FAK), Bcl-2-associated agonist of cell
      death (Bad) and B-cell CLL/lymphoma 2 (Bcl-2) proteins. rH significantly
      inhibited the cell viability and induced apoptosis in LC Hep-2 cells in a dose
      dependent manner, as compared with phosphate-buffered saline (PBS) as control.
      These results were accompanied by a decrease in the anti-apoptotic protein Bcl-2
      and an increase in the pro-apoptotic protein Bad. Moreover, rH dose-dependently
      inhibited the adhesion, migration and invasion of the Hep-2 cells, compared to
      the vehicle PBS. In addition, rH robustly suppressed angiogenesis in the CAM
      assay. Importantly, the expression of adhesion and angiogenesis-associated
      proteins FAK and VEGF-R was significantly downregulated by rH in a dose-dependent
      manner. The present findings demonstrate that rH exerts antitumor effects in Hep
      2 human laryngeal cancer cells via multiple mechanisms and suggests that
      targeting thrombin by rH is a potential strategy for the treatment of LC.

PMID- 25592111
TI  - Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK
      fusion positive lung cancer.
AB  - BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) patients with
      chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) are
      sensitive to the tyrosine kinase inhibitor crizotinib. We aimed to investigate
      the effects of combined radiotherapy and crizotinib in ALK-positive vs. wild type
      NSCLC models. MATERIAL AND METHODS: Clonogenic survival, proliferation and
      apoptosis of cells exposed to crizotinib and radiotherapy (photon and carbon
      ions) were evaluated in ALK mutation positive (ALK+; H3122) and negative (ALK-;
      A549 and LLC) NSCLC lines. The syngeneic mouse (LLC) and human (H3122) xenograft
      tumor models were further studied in vivo. Tumor growth kinetics, microvascular
      density (MVD), perfusion and proliferation were assessed. RESULTS: Crizotinib
      exerted potent and selective anti-proliferative and pro-apoptotic effects in ALK+
      H3122 cells which were augmented by radiotherapy. The synergistic effect of this
      combination in ALK+ NSCLC was confirmed by isobologram analysis. Crizotinib also
      sensitized H3122 cells to particle therapy with carbon ions. In H3122 xenografts,
      dual combination was most effective in reducing tumor proliferation, MVD and
      perfusion. In contrast, in the LLC model, crizotinib led only to a transient
      tumor growth inhibition and combined treatment was inferior to radiotherapy
      alone. CONCLUSIONS: Crizotinib elicits beneficial effects in combination with
      radiotherapy only in ALK-positive NSCLC.

PMID- 25592112
TI  - Predictive Factors of the Use of Systemic Therapy in Stage IV Colorectal Cancer:
      Who Gets Chemotherapy?
AB  - BACKGROUND: Chemotherapy improves survival in patients with stage IV colorectal
      cancer (CRC). Although in a clinical trial setting, strict eligibility criteria
      are used for chemotherapy, little is known about the use of chemotherapy in the
      general population. The study aims to assess clinicopathological variables that
      correlate with the use of chemotherapy in patients with stage IV CRC. METHODS: A
      retrospective cohort study involving patients with stage IV CRC, diagnosed
      between 1992 and 2005, in the province of Saskatchewan was carried out. A
      logistic regression analysis was performed to assess the correlation of various
      clinicopathological factors with the use of chemotherapy. RESULTS: A total of
      1,237 eligible patients were identified. Their median age was 70 years (range: 22
      98) and the male:female ratio was 1.3:1. 23.8% had an ECOG performance status
      (PS) of >=2 and 61.8% of the patients had a comorbid illness. 46.8% of the
      patients received chemotherapy. The multivariate logistic regression analysis
      revealed that an age of <65 years [odds ratio (OR) 3.82, 95% CI: 2.59-5.63],
      metastasectomy (OR 3.60, 95% CI: 1.82-7.10), normal albumin (OR 3.26, 95% CI:
      2.44-4.36), no comorbid illness (OR 2.87, 95% CI: 1.34-6.16), ECOG PS of <2 (OR
      2.72, 95% CI: 1.94-3.82), normal blood urea nitrogen (OR 2.24, 95% CI: 1.40
      3.59), palliative radiation (OR 2.03, 95% CI: 1.38-2.99), primary tumor resection
      (OR 2.00, 95% CI: 1.47-2.73), and the time period (OR 1.85, 95% CI: 1.41-2.42)
      were significantly correlated with the use of chemotherapy. CONCLUSIONS: The use
      of chemotherapy appears to be increasing in stage IV CRC. Patients treated with
      curative intention or who underwent primary tumor resection were more likely to
      receive chemotherapy. Despite a known benefit of chemotherapy in elderly
      patients, a differential use of chemotherapy was noted in this population.

PMID- 25592113
TI  - IL-37: a new player in immune tolerance.

PMID- 25592114
TI  - Cutaneous diphtheria: easy to be overlooked.

PMID- 25592115
TI  - PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR
      mutation.
AB  - Immunotherapy has become a crucial modality for non-small-cell lung cancer
      treatment. Recently, two immune checkpoints, PD-1 and PD-L1, have emerged as
      important targets for immunotherapy. Their antitumor efficacy has been confirmed
      by in vitro and in vivo studies. But the correlation between PD-1/PD-L1
      expression and EGFR expression was controversial and needs more evidences to
      support the combination of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors. 

PMID- 25592116
TI  - A Phase II Trial of Combined Chemotherapy with Oral S-1 and 24-Hour Infusions of
      Irinotecan plus Bevacizumab in Patients with Metastatic Colorectal Cancer.
AB  - OBJECTIVES: Protracted low-dose infusion of irinotecan has been suggested to
      enhance antitumor activity. A phase II study was conducted to evaluate the safety
      and efficacy of oral S-1 combined with 24-hour infusion of irinotecan and
      intravenous bevacizumab for metastatic colorectal cancer (MCRC). METHODS: The
      subjects were 79 patients with MCRC; 57 were chemotherapy naive. Irinotecan (125
      mg/m(2)) was administered as a 24-hour infusion on days 1 and 15, S-1 (80
      mg/m(2)) was administered orally on days 1-14, and bevacizumab (5.0 mg/kg) was
      given on days 1 and 15. The treatment was repeated every 4 weeks. RESULTS: Median
      follow-up was 20.0 months, and the mean number of cycles was 7. The overall
      response rate was 79.7% (95% CI, 69.2-88.0), 86.0% (95% CI, 74.2-93.7) for first
      line and 63.6% (95% CI, 40.7-82.8) for second-line treatment. The median
      progression-free survival was 16.4 months (95% CI, 13.9-21.0) for first-line and
      9.4 months (95% CI, 4.9-16.5) for second-line treatment. The median overall
      survival was not reached. Grade 3-4 toxicities were neutropenia (43%), leukopenia
      (20.3%), anorexia (19.0%), and diarrhea (10.1%). Toxicity was tolerable.
      CONCLUSIONS: Combination chemotherapy with oral S-1 and biweekly 24-hour
      infusions of irinotecan plus bevacizumab appears to be highly active and well
      tolerated both as first-line and second-line chemotherapy for MCRC.

PMID- 25592117
TI  - HyLiTE: accurate and flexible analysis of gene expression in hybrid and
      allopolyploid species.
AB  - BACKGROUND: Forming a new species through the merger of two or more divergent
      parent species is increasingly seen as a key phenomenon in the evolution of many
      biological systems. However, little is known about how expression of parental
      gene copies (homeologs) responds following genome merger. High throughput RNA
      sequencing now makes this analysis technically feasible, but tools to determine
      homeolog expression are still in their infancy. RESULTS: Here we present HyLiTE -
      a single-step analysis to obtain tables of homeolog expression in a hybrid or
      allopolyploid and its parent species directly from raw mRNA sequence files. By
      implementing on-the-fly detection of diagnostic parental polymorphisms, HyLiTE
      can perform SNP calling and read classification simultaneously, thus allowing
      HyLiTE to be run as parallelized code. HyLiTE accommodates any number of parent
      species, multiple data sources (including genomic DNA reads to improve SNP
      detection), and implements a statistical framework optimized for genes with low
      to moderate expression. CONCLUSIONS: HyLiTE is a flexible and easy-to-use program
      designed for bench biologists to explore patterns of gene expression following
      genome merger. HyLiTE offers practical advantages over manual methods and
      existing programs, has been designed to accommodate a wide range of genome merger
      systems, can identify SNPs that arose following genome merger, and offers
      accurate performance on non-model organisms.

PMID- 25592118
TI  - Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor
      Trap in a rabbit model.
AB  - PURPOSE: To determine intraocular pharmacokinetic properties of intravitreally
      injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model.
      METHODS: VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were
      enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately
      frozen at -80  degrees C. Concentration of VEGF-Trap in vitreous, aqueous humor,
      and retina/choroid was determined using an indirect enzyme-linked immunosorbent
      assay and analyzed to obtain pharmacokinetic properties. RESULTS: Maximum
      concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one
      compartment model of distribution was selected as the final model for all tissues
      studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and
      retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean
      residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve
      from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total
      exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9%
      of vitreous exposure, respectively. CONCLUSION: The vitreous half-life of VEGF
      Trap is 3.63 days. This is shorter than that of bevacizumab (6.99 days) and
      longer than that of ranibizumab (2.51 days), as shown in studies using the same
      experimental settings. The concentration of VEGF-Trap peaked at 1 h after
      injections in all eye tissues studied.

PMID- 25592119
TI  - Comparison of penetration depth in choroidal imaging using swept source vs
      spectral domain optical coherence tomography.
AB  - PURPOSE: To compare signal penetration depth and deep structure-visualization of
      swept source (SS) and spectral domain (SD)-optical coherence tomography (OCT)
      with and without enhanced depth imaging (EDI) and B-scan averaging modes.
      METHODS: Volume scans were obtained from 20 eyes of healthy volunteers by DRI OCT
      1, Spectralis using EDI and B-scan averaging, and Cirrus HD-OCT. The signal
      penetration depth was measured as the distance between the retinal pigment
      epithelium and the deepest visible anatomical structure at the foveal center.
      Visibility and contrast of the choroidoscleral junction and of vascular details
      within the choroid were assessed across the entire volume using an ordinal
      scoring scale. Outcome measures were compared using paired t-test and rank-sum
      test. RESULTS: The mean signal penetration depth was 498+/-114 MUm for
      Spectralis, 491+/-85 MUm for DRI OCT-1, and 123+/-65 MUm for Cirrus; P=0.9708
      Spectralis vs DRI OCT-1, P<0.0001 Spectralis vs Cirrus, and P<0.0001 DRI OCT-1 vs
      Cirrus. Mean ranks for visibility and contrast of the choroidoscleral junction
      were 3.83 for Spectralis, 3.98 for DRI OCT-1, and 2.00 for Cirrus; and 3.45 for
      Spectralis, 2.93 for DRI OCT-1, and 1.58 for Cirrus. Mean ranks for visibility
      and contrast of vascular details were 3.73 (Spectralis), 3.70 (DRI OCT-1), and
      2.23 (Cirrus); and 3.53 (Spectralis), 2.05 (DRI OCT-1), and 1.98 (Cirrus).
      CONCLUSION: Signal penetration depths are similar for SS-OCT and SD-OCT using EDI
      and frame averaging, and statistically significantly lower without EDI/averaging.
      Both SD-OCT using EDI/frame averaging and SS-OCT offer excellent visualization
      capabilities for volumetric imaging of the choroidoscleral interface.

PMID- 25592120
TI  - Acute corneal hydrops in keratoconus: a national prospective study of incidence
      and management.
AB  - PurposeTo determine incidence and management of acute corneal hydrops in the
      UK.MethodsWe used the BOSU report card system to survey cases of acute corneal
      hydrops in patients with keratoconus that occurred in the UK between November
      2009 and December 2010. Ophthalmologists who reported a case were sent an initial
      questionnaire, with a follow-up questionnaire after 6 months. We collected
      information on the demographics, complications, changes in visual acuity, and
      management. The 2011 National Census was used as a source for population and
      ethnicity in the UK.ResultsThere were 73 incident cases of acute corneal hydrops,
      with a response to the initial questionnaire for 64 (88%) patients and follow-up
      data at 6 months for 57 (78%) patients. For the 64 confirmed cases the median
      (interquartile range) age of onset was 31.9 (23.2, 41.3) years and 48 (75%) of
      the cases occurred in males. A total of 42 (66%) patients were white, 14 (22%)
      were South Asian, and 7 (11%) were black. The proportion of South Asian and black
      patients with acute corneal hydrops was significantly higher than in the general
      population (P<0.001). The minimum estimated annual incidence of acute corneal
      hydrops in patients with keratoconus was estimated to be 1.43 (1.10, 1.83) per
      1000. At 6 months following acute corneal hydrops a decision to proceed with
      keratoplasty had been made for 12 (20.3%) patients.ConclusionsThis is the first
      population-based estimate of the incidence of acute corneal hydrops in
      keratoconus. 

PMID- 25592121
TI  - Unintentional secondary exogenous corticosteroid exposure and central serous
      chorioretinopathy.
AB  - PURPOSE: The purpose of this study is to describe a possible association between
      unintentional secondary exogenous corticosteroid exposure and central serous
      chorioretinpathy (CSCR). METHODS: A retrospective review of three patients
      diagnosed with CSCR in one or both eyes and a history of possible unintentional
      secondary corticosteroid exposure. Clinical history, exam findings, optical
      coherence tomography, fluorescein angiography, and clinical course were reviewed.
      RESULTS: Three patients, who did not use corticosteroids, reported suspected
      unintentional secondary corticosteroid exposure from living with family members
      or partners using dermatologic corticosteroid cream and/or inhalers frequently.
      Two of the three patients had a history of recurrent CSCR, one patient involving
      both eyes. After taking precautions to avoid secondary corticosteroid exposure,
      all three patients had complete resolution of CSCR without further recurrence
      during follow-up ranging from 2 to 4 years. CONCLUSIONS: Patients with CSCR
      should be queried for both primary and possible unintentional secondary routes of
      corticosteroid exposure, which may contribute to this condition.

PMID- 25592122
TI  - Ophthalmic and molecular genetic findings in Kniest dysplasia.
AB  - PURPOSE: To study the variability of the ophthalmic phenotype in Kniest
      dysplasia. Kniest dysplasia is an inherited disorder associated with defects in
      type II collagen and characterised by short-trunked dwarfism, kyphoscoliosis, and
      enlarged joints with restricted mobility. Other features include marked hand
      arthropathy, cleft palate, hearing loss, and ocular abnormalities (myopia,
      abnormal vitreous, and high risk of developing retinal detachment). METHODS: Data
      from eight unrelated individuals with a clinical and molecular diagnosis of
      Kniest dysplasia are reported. Clinical assessment included an audiogram and
      ophthalmological examination in all but one patient who died in the immediate
      postnatal period. Sanger sequencing of the COL2A1 gene was performed. RESULTS:
      Six of the seven patients tested were high myopes with one patient being an
      emmetrope. Bilateral quandratic cataracts and subluxed lenses were noted in one
      subject. Variable but abnormal vitreous architecture was observed in all seven
      individuals tested. Six of the seven patients had significant hearing impairment
      and five of the seven patients exhibited clefting abnormalities. One patient had
      bilateral retinal detachments in his twenties. Six dominant disease-causing
      COL2A1 variants were detected. In three cases, testing of parental samples
      revealed that the disease-causing variant was not present in either parent.
      CONCLUSION: The ophthalmic features in Kniest dysplasia are very similar to those
      in other disorders of type II collagen such as Stickler syndrome. It is likely
      that different type II collagenopathies have a similar level of ocular morbidity
      and regular ophthalmologic examination is recommended. Kniest dysplasia is
      associated with heterozygous COL2A1 mutations that are frequently de novo.

PMID- 25592123
TI  - Prevalence and incidence of blindness and other degrees of sight impairment in
      patients treated for neovascular age-related macular degeneration in a well
      defined region of the United Kingdom.
AB  - AIMS: This study aimed to evaluate the incidence and prevalence of blindness,
      sight impairment, and other visual acuity (VA) states in patients receiving
      ranibizumab for neovascular age-related macular degeneration (nAMD) in
      Gloucestershire. METHODS: Serial VA and injection data for all treatment-naive
      patients receiving their first intravitreal injections of ranibizumab for nAMD in
      the Gloucestershire National Health Service Ophthalmology department between 2008
      and 2010 were extracted from an electronic medical record system. RESULTS: The
      prevalence of blindness (VA in the better-seeing eye <=25 Early Treatment
      Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal
      injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight
      impairment (VA in the better-seeing eye 26-39 ETDRS letters) increased from 4.1%
      at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab
      treatment for nAMD in people aged >=50 years in Gloucestershire was 111 people
      per 100 000 population in 2009, and 97 people in 2010. The incidence of patients
      meeting the visual criteria for blindness and sight impairment registration from
      treated nAMD in people aged >=50 years in Gloucestershire was 3.5 and 9.7 people,
      respectively per 100 000 population in 2010. CONCLUSION: This is the first real
      world study on the incidence and prevalence of eligibility for blindness and
      sight impairment registration in treated nAMD in the UK based on VA data. The
      incidence and prevalence of eligibility for certification of blindness or sight
      impairment in patients treated with ranibizumab for nAMD is low in
      Gloucestershire, with only 3.6% of the incident population progressing to
      blindness in 2010.

PMID- 25592124
TI  - Outcomes following cataract surgery in choroideremia.
AB  - PurposeTo present a case series of cataract surgery outcomes in choroideremia
      eyes with an emphasis on the safety of this common operation in advanced stages
      of the disease.MethodsA single centre retrospective interventional case series
      comprising six patients with varying degrees of visual loss secondary to
      choroideremia underwent cataract surgery at a single tertiary eye hospital. Pre-
      and post-operative best-corrected Snellen visual acuity, spectral domain optical
      coherence tomography (SD-OCT), and slit lamp examination were performed together
      with fundus autofluorescence (FAF) and colour fundus photographs.The prevalence
      of intra- or post-operative complications, post-operative visual outcome, and
      change in central macular thickness were recorded.ResultsThe pre-operative best
      corrected Snellen visual acuity in the operated eyes ranged from 6/12 (20/40) to
      PL. All but one patient had either an objective or a subjective improvement in
      visual acuity. There was no evidence of retinal phototoxicity or post-operative
      cystoid macular oedema (CMO). Three patients developed early capsular
      fibrosis.ConclusionsAlthough the residual functioning retina in choroideremia
      patients may be potentially vulnerable, this report finds no evidence of
      iatrogenic vision loss after uncomplicated cataract surgery. This suggests that
      cataract surgery may be performed safely in choroideremia patients, although a
      guarded prognosis for visual improvement should be emphasized in the informed
      consent. 

PMID- 25592125
TI  - Retained silicone tip of diamond-dusted membrane scraper during vitrectomy in a
      valved cannula system.
AB  - PURPOSE: To report a complication of retained silicone tip from a diamond-dusted
      membrane scraper (DDMS) that occurred while using a valved cannula vitrectomy
      system. METHOD: Retrospective review of three cases that underwent 23 gauge (G)
      sutureless vitrectomy for idiopathic macular hole (cases 1 and 2) and myopic
      macular schisis (case 3). RESULTS: In all three cases following a standard
      vitrectomy, the internal limiting membrane (ILM) peeling was initiated by using a
      23G DDMS. During the insertion of the DDMS, the flexible silicone tip of the 23G
      DDMS was detached from the metal shaft and was retained in the 23G valve system
      and in case 3, the silicone tip got dislodged from the valve onto the retina.
      Subsequent ILM peeling was completed by using an end-gripping forceps. All
      underwent intravitreal gas injection at the end. No other complications were
      noted. CONCLUSION: These three cases demonstrate an uncommon complication of
      retained silicone tip within the valved cannula vitrectomy system and this
      complication should be considered while using flexible instruments in valved
      cannula systems.

PMID- 25592126
TI  - Transient retinal artery occlusion during phacoemulsification cataract surgery.

PMID- 25592128
TI  - Reply: Transient retinal artery occlusion during phacoemulsification cataract
      surgery.

PMID- 25592127
TI  - Wide-field imaging and OCT vs clinical evaluation of patients referred from
      diabetic retinopathy screening.
AB  - PURPOSE: Compare wide-field Optomap imaging and optical coherence tomography
      (OCT) with clinical examination in diabetic retinopathy (DR). METHODS: Patients
      referred from Diabetic Eye Screening Programmes to three centres underwent
      dilated ophthalmoscopy and were assigned a DR grade. Wide-field colour imaging
      and OCT were then examined by the same clinician at that visit and a combined
      grade was assigned. Independent graders later reviewed the images and assigned an
      imaging-only grade. These three grades (clinical, combined, and imaging) were
      compared. The method that detected the highest grade of retinopathy, including
      neovascularisation, was determined. RESULTS: Two thousand and forty eyes of 1023
      patients were assessed. Wide-field imaging compared with clinical examination had
      a sensitivity and specificity of 73% and 96%, respectively, for detecting
      proliferative DR, 84% and 69% for sight-threatening DR, and 64% and 90% for
      diabetic macular oedema. Imaging alone found 35 more eyes with new vessels (19%
      of eyes with new vessels) and the combined grade found 14 more eyes than clinical
      examination alone. CONCLUSIONS: Assessment of wide-field images and OCT alone
      detected more eyes with higher grades of DR compared with clinical examination
      alone or when combined with imaging in a clinical setting. The sensitivity was
      not higher as the techniques were not the same, with imaging alone being more
      sensitive. Wide-field imaging with OCT could be used to assess referrals from DR
      screening to determine management, to enhance the quality of assessment in
      clinics, and to follow-up patients whose DR is above the screening referral
      threshold but does not actually require treatment.

PMID- 25592129
TI  - Macular and peripapillary retinal nerve fibre layer thickness in patients with
      cyanotic congenital heart disease.
AB  - PURPOSE: To evaluate macular and retinal nerve fibre layer (RNFL) measurements in
      patients with cyanotic congenital heart disease (cCHD) using spectral domain
      optical coherence tomography (OCT). PATIENTS AND METHODS: Thirty patients with
      cCHD (18 females and 12 males, mean age 10.9 years) and 60 healthy controls (35
      females and 25 males, mean age 11.2 years) underwent complete ophthalmologic
      examination and OCT measurements of macular and peripapillary RNFL thickness.
      RESULTS: Patients with cCHD had significantly thinner measurements in all macular
      subfields compared with healthy controls (P<0.001). There was no significant
      difference in peripapillary RNFL thickness between the two groups, with the
      exception of the upper quadrant, for which thickness measurements were higher in
      patients with cCHD (P=0.021). CONCLUSIONS: Patients with cCHD showed a
      significant decrease in macular thickness and a thickened superior quadrant RNFL
      thickness when compared with healthy controls. This may represent the damage
      caused by the effect of hypoxia.

PMID- 25592130
TI  - Factors affecting the repeatability of gamma camera calibration for quantitative
      imaging applications using a sealed source.
AB  - Several applications in nuclear medicine require absolute activity quantification
      of single photon emission computed tomography images. Obtaining a repeatable
      calibration factor that converts voxel values to activity units is essential for
      these applications. Because source preparation and measurement of the source
      activity using a radionuclide activity meter are potential sources of
      variability, this work investigated instrumentation and acquisition factors
      affecting repeatability using planar acquisition of sealed sources. The
      calibration factor was calculated for different acquisition and geometry
      conditions to evaluate the effect of the source size, lateral position of the
      source in the camera field-of-view (FOV), source-to-camera distance (SCD), and
      variability over time using sealed Ba-133 sources. A small region of interest
      (ROI) based on the source dimensions and collimator resolution was investigated
      to decrease the background effect. A statistical analysis with a mixed-effects
      model was used to evaluate quantitatively the effect of each variable on the
      global calibration factor variability. A variation of 1 cm in the measurement of
      the SCD from the assumed distance of 17 cm led to a variation of 1-2% in the
      calibration factor measurement using a small disc source (0.4 cm diameter) and
      less than 1% with a larger rod source (2.9 cm diameter). The lateral position of
      the source in the FOV and the variability over time had small impacts on
      calibration factor variability. The residual error component was well estimated
      by Poisson noise. Repeatability of better than 1% in a calibration factor
      measurement using a planar acquisition of a sealed source can be reasonably
      achieved. The best reproducibility was obtained with the largest source with a
      count rate much higher than the average background in the ROI, and when the SCD
      was positioned within 5 mm of the desired position. In this case, calibration
      source variability was limited by the quantum noise. 

PMID- 25592132
TI  - First principles characterization of silicate sites in clay surfaces.
AB  - Aluminosilicate clays like Montmorillonite (MMT) and Muscovite Mica (MT) have
      siloxane cavities on the basal plane. The hydroxyl groups localized in these
      cavities and van der Waals (vdW) forces contribute significantly to adsorption
      processes. However, the basal sites are found to be difficult to characterize
      experimentally. Here, (001) surfaces of MMT and MT clays were investigated using
      first-principles calculations to understand how these silicate surface sites are
      influenced by hydroxyl groups and the effective role of inner layer vdW
      interactions. Based on density-functional theory (DFT) within the generalized
      gradient approximation (GGA), different types of exchange-correlation functionals
      were tested to check the effect of vdW dispersion correction. Noncontact atomic
      force microscopy (nc-AFM), X-ray absorption spectroscopy (XAS) in the near-edge
      region and solid-state nuclear magnetic resonance (SS-NMR) spectroscopy were
      simulated. In both clays, the oxygen surface sites are directly affected by the
      intralayer interaction through hydroxyl groups. Our results indicated that the
      chemical environment of the hydroxyl groups is distinct in the MMT and MT
      structures. The vdW correction was essential for a better description of the
      surface oxygen sites and correctly describes the similarity between both clays.
      Particularly, the bulk apical oxygen sites in the MT structure are less
      influenced by vdW interaction. Compared to MMT, the silicon surface sites of MT
      are more sensitive to the intralayer changes in Si-Oapical-Al and with less
      effect of the hydroxyl groups. These results provide a clear understanding of
      influence of the siloxane cavity on the oxygen and silicon surface sites in
      aluminosilicates. 

PMID- 25592131
TI  - Hessian fly larval feeding triggers enhanced polyamine levels in susceptible but
      not resistant wheat.
AB  - BACKGROUND: Hessian fly (Mayetiola destructor), a member of the gall midge
      family, is one of the most destructive pests of wheat (Triticum aestivum)
      worldwide. Probing of wheat plants by the larvae results in either an
      incompatible (avirulent larvae, resistant plant) or a compatible (virulent
      larvae, susceptible plant) interaction. Virulent larvae induce the formation of a
      nutritive tissue, resembling the inside surface of a gall, in susceptible wheat.
      These nutritive cells are a rich source of proteins and sugars that sustain the
      developing virulent Hessian fly larvae. In addition, on susceptible wheat, larvae
      trigger a significant increase in levels of amino acids including proline and
      glutamic acid, which are precursors for the biosynthesis of ornithine and
      arginine that in turn enter the pathway for polyamine biosynthesis. RESULTS:
      Following Hessian fly larval attack, transcript abundance in susceptible wheat
      increased for several genes involved in polyamine biosynthesis, leading to higher
      levels of the free polyamines, putrescine, spermidine and spermine. A concurrent
      increase in polyamine levels occurred in the virulent larvae despite a decrease
      in abundance of Mdes-odc (ornithine decarboxylase) transcript encoding a key
      enzyme in insect putrescine biosynthesis. In contrast, resistant wheat and
      avirulent Hessian fly larvae did not exhibit significant changes in transcript
      abundance of genes involved in polyamine biosynthesis or in free polyamine
      levels. CONCLUSIONS: The major findings from this study are: (i) although
      polyamines contribute to defense in some plant-pathogen interactions, their
      production is induced in susceptible wheat during interactions with Hessian fly
      larvae without contributing to defense, and (ii) due to low abundance of
      transcripts encoding the rate-limiting ornithine decarboxylase enzyme in the
      larval polyamine pathway the source of polyamines found in virulent larvae is
      plausibly wheat-derived. The activation of the host polyamine biosynthesis
      pathway during compatible wheat-Hessian fly interactions is consistent with a
      model wherein the virulent larvae usurp the polyamine biosynthesis machinery of
      the susceptible plant to acquire nutrients required for their own growth and
      development.

PMID- 25592133
TI  - Efficacy of combined treatment with alendronate (ALN) and eldecalcitol, a new
      active vitamin D analog, compared to that of concomitant ALN, vitamin D plus
      calcium treatment in Japanese patients with primary osteoporosis.
AB  - Combined treatment with alendronate and eldecalcitol was found to be more
      effective in reducing the bone turnover markers and increasing bone mineral
      density than alendronate treatment with vitamin D3 and calcium supplementation in
      the osteoporotic patients. INTRODUCTION: We compared the clinical efficacy and
      safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with
      those of treatment with ALN plus vitamin D and calcium (ALN + VitD). METHODS:
      Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN +
      VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD
      (L-BMD) at patient's last visit. Secondary endpoints included the differences in
      BMD at other sites and the bone turnover marker (BTM) levels. RESULTS: L-BMD,
      total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41,
      and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18% in the ALN + VitD
      group, respectively. Inter-group differences of the L-BMD and total hip BMD
      values were not significant. The increase of the FN-BMD was larger in the ALN +
      ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the
      ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of
      the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD
      group only. The increases of the FN-BMD in patients with lower baseline values of
      type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were
      significantly larger in the ALN + ELD group than the other group. CONCLUSION:
      Combination treatment of ALN plus ELD was more effective in reducing the BTMs and
      increasing the FN-BMD than ALN treatment with vitamin D3 and calcium.

PMID- 25592134
TI  - Reliability and validity of lower extremity computed tomography as a screening
      tool for osteoporosis.
AB  - We evaluated the correlation between central bone mineral density (BMD) and
      peripheral bone attenuation using lower extremity computed tomography (CT). A
      good correlation was found between lower extremity CT and central BMD suggesting
      that CT is useful for screening osteoporosis, and that peripheral bone
      attenuation adequately reflects central BMD. INTRODUCTION: This study aimed to
      evaluate the reliability and validity of CT as a screening tool for osteoporosis
      and to estimate the correlation between central BMD and peripheral bone
      attenuation using lower extremity CT. METHODS: In total, 292 patients who
      underwent a lower extremity, lumbar spine, or abdomen and pelvic CT scan within a
      3-month interval of a dual-energy X-ray absorptiometry (DEXA) examination were
      included. Following reliability testing, bone attenuation of the L1, L2, L3, L4,
      femoral head, femoral neck, greater trochanter, distal femur, proximal tibia,
      distal tibia, and talus was measured by placing a circular region of interest on
      the central part of each bony region on a coronal CT image. Partial correlation
      was used to assess the correlation between CT and DEXA after adjusting for age
      and body mass index. RESULTS: In terms of reliability, all bone attenuation
      measurements, except the femoral neck, showed good to excellent interobserver
      reliability (intraclass correlation coefficients, 0.691-0.941). In terms of
      validity, bone attenuation of the L1 to L4, femoral neck, and greater trochanter
      on CT showed significant correlations with BMD of each area on DEXA (correlation
      coefficients, 0.399-0.613). Bone attenuation of the distal tibia and talus on CT
      showed significant correlations with BMD of all parts on DEXA (correlation
      coefficients, 0.493-0.581 for distal tibia, 0.396-0.579 for talus). CONCLUSION:
      Lower extremity CT is a useful screening tool for osteoporosis, and peripheral
      bone attenuation on lower extremity CT adequately reflects central BMD on DEXA.

PMID- 25592135
TI  - Differential expression of HIF-1alpha, AQP-1, and VEGF under acute hypoxic
      conditions in the non-ventilated lung of a one-lung ventilation rat model.
AB  - AIMS: One-lung ventilation (OLV) is a standard practice in thoracic surgery.
      However, OLV can give rise to arterial hypoxemia. Hypoxia-inducible transcription
      factor-1 alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and
      aquaporin-1 (AQP-1) may be involved in arterial hypoxemia and contribute to
      cellular injury. Therefore, in the present study, these moieties were
      investigated in an OLV rat model. MAIN METHODS: Forty Sprague-Dawley (S-D) rats
      were randomly divided into four groups: right lung mechanical ventilation for 0.5
      h (Group A); 1 h (Group B); 2 h (Group C) and mechanical ventilation of both
      lungs (control group). Rat lung tissue was examined using electron microscopy.
      Serum and lung tissue levels of VEGF were measured by ELISA, Western blot
      analyses were used to detect the protein expression of HIF-1alpha and
      immunohistochemical staining and real-time polymerase chain reaction (PCR) were
      performed to examine protein expression and gene levels, respectively, of VEGF
      and AQP-1 after hypoxia. KEY FINDINGS: Electron microscopy revealed that
      increased duration of OLV was correlated with greater destruction of the non
      ventilated lung. The protein expression of HIF-1alpha was significantly increased
      in the non-ventilated lungs of the experimental hypoxia groups (A-C) compared to
      the control group, whereas VEGF and AQP-1 protein expression and gene levels were
      decreased in the non-ventilated lungs of the hypoxia groups (A-C) compared to the
      control group. SIGNIFICANCE: The OLV caused hypoxia in the non-ventilated lung
      and subsequent injury. The altered expression of HIF-1alpha, VEGF, and AQP-1 may
      be involved in the pathological process of lung injury caused by hypoxia.

PMID- 25592136
TI  - Investigating degeneration of the retina in young and aged tau P301L mice.
AB  - AIMS: Tau is a microtubule-binding protein facilitating the stability of the
      cytoskeleton. It is important for neurons as several neurodegenerative diseases
      involve hyperphosphorylation and aggregation of tau. It is known that mutated tau
      P301L results in aggregation of tau proteins, leading to neuronal loss in the
      brain. The aim of this study was to investigate the effect of tau mutation on the
      retina using a transgenic tau P301L mouse model. MAIN METHODS: Morphometric
      analysis was utilized to quantify the neurodegenerative changes, including the
      thickness of the inner nuclear layer (INL), and the density and size of retinal
      ganglion cells (RGCs). Sections of retina tissue stained by hematoxylin and eosin
      (H&E) and immunohistochemistry were analyzed. Comparisons were made between the
      tau P301L mice and control mice, as well as between different age groups. KEY
      FINDINGS: A significant decrease in the thickness of the INL in tau P301L mice
      was found when compared with that of control mice. The effect was more pronounced
      in the peripheral area, and the effect increased with age. Regarding density of
      RGCs, tau P301L mice showed a similar age-related decline as in control mice.
      Furthermore, the RGCs from tau P301L mice increased in size with age, and the
      RGCs from control mice decreased in size with age. SIGNIFICANCE: Tau may be an
      age-independent factor of accelerated neurodegeneration, with effects differing
      by types of neurons and regions of the retina.

PMID- 25592137
TI  - Ameliorative potential of vitamin P and digoxin in ischemic-reperfusion induced
      renal injury using the Langendorff apparatus.
AB  - AIMS: The present study has been designed to investigate the ameliorative
      potential of vitamin P, and digoxin in ischemic-reperfusion (I/R)-induced renal
      injury in isolated rat kidney preparations by using the Langendorff apparatus.
      MAIN METHODS: Vitamin P (50 and 100 mg/kg; p.o.) was administered to rats for 5
      consecutive days. On the 6th day, isolated kidneys were subjected to 30 min of
      ischemia followed by 120 min of reperfusion by constant flow (8 ml/min). The
      total renal effluent was collected at various time intervals (i.e., basal, 0, 15,
      30, 45 and 60 min). In addition, urea, creatinine, and creatine kinase (CK)
      activity were evaluated in the renal effluent, and TBARS, GSH, and Na(+)-K(+)
      ATPase activity were evaluated in tissue. KEY FINDINGS: I/R of renal tissue
      produced a rise in the activity of CK and the levels of urea and creatinine in
      the renal effluent, as well as in the activity of Na(+)-K(+)-ATPase and levels of
      TBARS in the tissue. Additionally, it decreased GSH levels when compared with the
      sham control group. Digoxin served as positive control in the present work.
      Treatment with vitamin P (100 mg/kg), and digoxin (500 MUg/kg) produced a
      significant (P<0.05) ameliorative effect against the I/R induced changes in
      biomarkers. SIGNIFICANCE: The renoprotective effect of vitamin P is caused by its
      inhibition of Na(+)-K(+)-ATPase activity, which subsequently results in free
      radical scavenging and anti-infarct properties. Therefore, this vitamin can be
      useful in the management of renovascular disorders.

PMID- 25592138
TI  - PSTK is a novel gene associated with early lung injury in Paraquat Poisoning.
AB  - AIMS: Paraquat Poisoning (PQ) can cause illness and death, and its main causes of
      mortality are acute respiratory failure and lung fibrosis. Early recognition of
      this condition and early treatment are vital. Thus, it is of importance to target
      the key genes controlling pathogenesis in the early stage of PQ. MAIN METHODS:
      C57BL/6 mice were used for Paraquat intragastric administration as a model of PQ.
      Following a gene chip-based screening, the change of gene expression in the lung
      was further validated by bioinformatic analyses, co-expression network
      construction and real-time RT-PCR, Western blot and immunofluorescence assays.
      KEY FINDINGS: 2287 genes with differential expression were identified at the very
      early stage of PQ. From these, 76 genes that were linked to mitochondrion
      function were further pursued. Among these genes, PSTK was a phosphorylase kinase
      which serves a protective role in oxidative stress lung damage. PSTK was the
      central gene in a 30-gene network that is important for mitochondrial complex I
      assembly, mitochondrial apoptosis and mitochondrial fatty acid beta-oxidation,
      suggesting that they could conceivably be related to the pathogenesis of PQ
      induced lung damage. Lastly, we confirmed that PSTK was lowered in rodent lungs
      following PQ. SIGNIFICANCE: PSTK emerges as a central gene in a network of
      mitochondrial function genes in PQ exposed mice. The functional role of PSTK in
      PQ induced lung injury warrants further examination.

PMID- 25592140
TI  - [Effect of intraoperative esmolol infusion on anesthetic, analgesic requirements
      and postoperative nausea-vomitting in a group of laparoscopic cholecystectomy
      patients].
AB  - PURPOSE: Postoperative pain and nausea/vomitting (PNV) are common in laparoscopic
      cholecystectomy patients. Sympatholytic agents might decrease requirements for
      intravenous or inhalation anesthetics and opioids. In this study we aimed to
      analyze effects of esmolol on intraoperative anesthetic-postoperative analgesic
      requirements, postoperative pain and PNV. METHODS: Sixty patients have been
      included. Propofol, remifentanil and vecuronium were used for induction. Study
      groups were as follows; I - Esmolol infusion was added to maintenance anesthetics
      (propofol and remifentanil), II - Only propofol and remifentanil was used during
      maintenance, III - Esmolol infusion was added to maintenance anesthetics
      (desflurane and remifentanil), IV - Only desflurane and remifentanil was used
      during maintenance. They have been followed up for 24h for PNV and analgesic
      requirements. Visual analog scale (VAS) scores for pain was also been evaluated.
      RESULTS: VAS scores were significantly lowest in group I (p=0.001-0.028). PNV
      incidence was significantly lowest in group I (p=0.026). PNV incidence was also
      lower in group III compared to group IV (p=0.032). Analgesic requirements were
      significantly lower in group I and was lower in group III compared to group IV
      (p=0.005). Heart rates were significantly lower in esmolol groups (group I and
      III) compared to their controls (p=0.001) however blood pressures were similar in
      all groups (p=0.594). Comparison of esmolol groups with controls revealed that
      there is a significant decrease in anesthetic and opioid requirements (p=0.024
      0.03). CONCLUSION: Using esmolol during anesthetic maintenance significantly
      decreases anesthetic-analgesic requirements, postoperative pain and PNV.

PMID- 25592139
TI  - Involvement of peroxisome proliferator-activated receptors in cardiac and
      vascular remodeling in a novel minipig model of insulin resistance and
      atherosclerosis induced by consumption of a high-fat/cholesterol diet.
AB  - BACKGROUND: A long-term high-fat/cholesterol (HFC) diet leads to insulin
      resistance (IR), which is associated with inflammation, atherosclerosis (AS),
      cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator
      activated receptors (PPARs) and nuclear factor KB (NF-kappaB) are involved in the
      development of IR-AS. Thus, we elucidated the pathological molecular mechanism of
      IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. METHODS:
      Male Tibetan minipigs were fed either a normal diet or an HFC diet for 24 weeks.
      Thereafter, the minipigs were tested for physiological and biochemical blood
      indices, blood pressure, cardiac function, glucose tolerance, heart rate
      variability (HRV), and PPAR-associated gene and protein expression levels.
      RESULTS: HFC-fed minipigs exhibited IR through increased body weight, fasting
      blood glucose levels, plasma cholesterol and its composition, and insulin and
      free fatty acid (FFA) levels; decreased insulin sensitivity; impaired glucose
      tolerance; and hypertension. Increased C-reactive protein (CRP) levels, cardiac
      dysfunction, depressed HRV, and the up-regulation of PPAR expression in the
      abdominal aorta concomitant with down-regulation in the heart tissue were
      observed in HFC-fed minipigs. Furthermore, the levels of NF-kappaBp65, IL-1beta,
      TNF-alpha, MCP-1, VCAM-1, ICAM-1, MMP-9, and CRP proteins were also significantly
      increased. CONCLUSIONS: These data suggest that HFC-fed Tibetan minipigs develop
      IR and AS and that PPARs are involved in cardiovascular remodeling and impaired
      function.

PMID- 25592141
TI  - Comparing end-of-life practices in different policy contexts: a scoping review.
AB  - OBJECTIVES: End-of-life policy reforms are being debated in many countries.
      Research evidence is used to support different assumptions about the effects of
      public policies on end-of-life practices. It is however unclear whether reliable
      international practice comparisons can be conducted between different policy
      contexts. Our aim was to assess the feasibility of comparing similar end-of-life
      practices in different policy contexts. METHODS: This is a scoping review of
      empirical studies on medical end-of-life practices. We developed a descriptive
      classification of end-of-life practices that distinguishes practices according to
      their legal status. We focused on the intentional use of lethal drugs by
      physicians because of international variations in the legal status of this
      practice. Bibliographic database searches were supplemented by expert
      consultation and hand searching of reference lists. The sensitivity of the search
      strategy was tested using a set of 77 articles meeting our inclusion criteria.
      Two researchers extracted end-of-life practice definitions, study methods and
      available comparisons across policy contexts. Canadian decision-makers were
      involved to increase the policy relevance of the review. RESULTS: In sum, 329
      empirical studies on the intentional use of lethal drugs by doctors were
      identified, including studies from 19 countries. The bibliographic search
      captured 98.7% of studies initially identified as meeting the inclusion criteria.
      Studies on the intentional use of lethal drugs were conducted in jurisdictions
      with permissive (62%) and restrictive policies (43%). The most common study
      objectives related to the frequency of end-of-life practices, determinants of
      practices, and doctors' adherence to regulatory standards. Large variations in
      definitions and research methods were noted across studies. The use of a
      descriptive classification was useful to translate end-of-life practice
      definitions across countries. A few studies compared end-of-life practice in
      countries with different policies, using consistent research methods. We
      identified no comprehensive review of end-of-life practices across different
      policy contexts. CONCLUSIONS: It is feasible to compare end-of-life practices in
      different policy contexts. A systematic review of international evidence is
      needed to inform public deliberations on end-of-life policies and practice.

PMID- 25592142
TI  - alpha-Viniferin-Induced Structural and Functional Alterations in Raillietina
      echinobothrida, a Poultry Tapeworm.
AB  - alpha-Viniferin, an active component of the plant Carex baccans L., is known for
      its anticancer, antidiabetic, and anti-inflammatory properties. In Northeast
      India, different tribes traditionally consume C. baccans to control intestinal
      helminth infections. Therefore, the present study was carried out to assess the
      extent of tegumental alteration caused by alpha-viniferin in Raillietina
      echinobothrida, a widely prevalent poultry helminth in northeast India. Helminths
      were exposed in vitro to various doses of alpha-viniferin (50, 100, and 200 uM/mL
      of physiological buffered saline) and their motility and mortality were recorded.
      Stereoscan observations on the parasite exposed to the active compound showed
      extensive distortion and destruction of the surface fine topography of the
      tegument compared with controls. The compound also caused extensive damage to the
      tegument by disintegration of microtriches, disorganization of muscle bundles,
      and loss of cellular organelles combined with distortion and disruption of the
      plasma membrane, nuclear membrane, nucleolus, mitochondrial membrane, and
      cristae. Histochemical and biochemical studies carried out parasites exposed to
      alpha-viniferin revealed a decline in the activity of vital tegumental enzymes
      like acid phosphatase, alkaline phosphatase, and adenosine triphosphatase.
      Extensive structural and functional alterations observed in the treated parasites
      are indicative of efficient cestocidal activity of the compound.

PMID- 25592143
TI  - "Both Sides of the Wheelchair": The Views of Individuals with, and Parents of
      Individuals with Friedreich Ataxia Regarding Pre-symptomatic Testing of Minors.
AB  - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder
      characterized by variable age of onset, with no treatment proven to alter its
      natural history. Siblings of individuals with FRDA have a 25 % risk of developing
      the condition, raising issues around genetic testing of asymptomatic minors.
      There is a lack of professional consensus and limited empirical evidence to
      support provision or refusal of testing. This study aimed to ascertain the
      opinions of individuals with and parents of individuals with FRDA regarding pre
      symptomatic testing of minors. A qualitative research approach using semi
      structured interviews and thematic analysis was employed. Interviews with ten
      individuals with FRDA, and ten parents of individuals with FRDA were conducted,
      recorded, transcribed and analyzed. Four findings emerged. First, a number of
      arguments for and against testing minors were identified. Second, strong support
      existed from parents about the parental right to test their at-risk immature
      children, but individuals with FRDA were of mixed opinions. Third, participants
      felt it was not the clinician's role to make a final decision about whether
      testing occurs. Finally, a specific issue of concern regarding testing was what
      and when to tell at-risk children about the test result. The findings highlight a
      dilemma of how to manage the desires of some individuals and families affected by
      FRDA to access testing, when there is a lack of professional consensus due to
      differing opinions regarding autonomy, confidentiality and risk of harm. Research
      regarding the impact of testing and the views of at-risk individuals and
      clinicians is required so an appropriate framework for dealing with this
      contentious issue is developed. 

PMID- 25592144
TI  - Association of Researcher Characteristics with Views on Return of Incidental
      Findings from Genomic Research.
AB  - Whole exome/ genome sequencing (WES/WGS) is now commonly used in research and is
      increasingly used in clinical care to identify the genetic basis of rare and
      unknown diseases. The management of incidental findings (IFs) generated through
      these analyses is debated within the research community. To examine how views
      regarding genomic research IFs are associated with researcher characteristics and
      experiences, we surveyed genetic professionals and assessed the effect of
      professional background and experience on their opinions. Researchers who did not
      have clinical training, provide clinical care to research participants, or have
      prior experience returning research results were in general more inclined to
      offer return of IFs than their colleagues with these characteristics.
      Understanding this will be important to fully appreciate the impact that policies
      on return of genetic IFs could have on participants, researchers, and genomic
      research. 

PMID- 25592145
TI  - Prospective evaluation of the added value of imaging within the Dutch National
      Diagnostic Appendicitis Guideline--do we forget our clinical eye?
AB  - BACKGROUND: Annually 16,000 appendectomies are performed in the Netherlands, of
      which 15-20% are negative. In 2010, to reduce this unacceptable percentage of
      superfluous appendectomies, the Dutch Association for Surgery introduced the
      'Appendicitis Guideline'. This guideline recommends the use of imaging. In this
      observational prospective study the added value of imaging in everyday clinical
      practice is evaluated. METHODS: All patients with suspected appendicitis were
      included at the emergency department of a Dutch teaching hospital during the
      period from September 2011 to May 2012 (n = 350; 237 adults and 113 children
      under 18 years). Adherence to the guideline was evaluated. RESULTS: 75 Patients
      (21%) were not referred for imaging because of a low suspicion or alternative
      diagnosis. In 16 patients (5%) the guideline was not followed. Of the 259
      patients (74%) who underwent ultrasonography, 105 (30%) also underwent computed
      tomography (CT). 127 appendectomies were performed, showing appendicitis in 112
      patients (88%); 15 appendectomies (12%) were negative. In the latter group, 12
      were performed after false positive imaging results, and 3 following inconclusive
      imaging results. CONCLUSION: When using imaging in the diagnosis of appendicitis,
      the percentage of negative appendectomies remains close to the percentage
      declared as unacceptable by the publishers of the guideline.

PMID- 25592146
TI  - Limitations of free-form-text diagnostic requisitions as a tool for evaluating
      adherence to appropriate use criteria for transthoracic echocardiography.
AB  - BACKGROUND: Monitoring the adherence to Appropriateness Use Criteria (AUC) has
      been identified as an important component for the accreditation of
      echocardiography laboratories. Referral requisitions are a logical tool to
      rapidly determine the appropriateness of transthoracic echocardiography (TTE)
      referrals, however data is lacking. We investigated whether standard free-form
      text TTE referral requisitions can be used to evaluate AUC adherence. METHODS:
      Consecutive TTE referral requisitions to the University of Ottawa Heart Institute
      echocardiography laboratory were reviewed over a four-week period. Indication on
      the requisition was matched with the relevant indication on the 2011 American
      College of Cardiology Foundation (ACCF) AUC. Requisitions that did not provide
      sufficient information to identify the relevant AUC indication were identified as
      inadequate. For inadequate requisitions, reason for the referral was clarified
      through medical records and referring physicians. RESULTS: Of the 1303
      requisitions, 26.2% did not provide adequate information to determine adherence
      to AUC, despite a non-adherence (inappropriate) rate of only 6.1% in the referral
      population. Indication for referral, physician specialty, outpatient status, and
      prior echocardiogram were independent predictors of inadequate requisitions (p <
      0.001, respectively). The most common reasons for inadequate requisitions were a
      failure to report: 1) change in clinical status, 2) date of a prior
      echocardiogram, and 3) type and/or severity of a valve lesion. Inclusion of this
      information would have decreased the inadequacy rate by 56%. CONCLUSION: In a
      large, academic echocardiography laboratory, over one quarter of free-form-text
      TTE requisitions are inadequate to evaluate AUC adherence. Structured requisition
      formats requiring AUC-relevant information are needed to facilitate the practical
      application of AUC in the echocardiography laboratory.

PMID- 25592147
TI  - Novel antitussive effect of suplatast tosilate in guinea pigs.
AB  - We studied the antitussive effects of suplatast, a Th2 cytokine inhibitor, and
      compared them with the effects of codeine using an experimental cough model in
      guinea pigs. Suplatast and codeine dose-dependently inhibited cough caused by
      mechanical stimulation of the larynx, but they did not inhibit cough caused by
      mechanical stimulation of the bifurcation of the trachea. In guinea pigs with
      bronchitis, suplatast had an antitussive effect on cough caused by stimulation of
      the larynx, whereas codeine did not inhibit such cough. In SO2-exposed guinea
      pigs, suplatast tended to inhibit cough caused by mechanical stimulation of the
      tracheal bifurcation. Further, suplatast inhibited citric acid-induced cough
      augmented by pretreatment with an angiotensin-converting enzyme inhibitor,
      whereas codeine did not inhibit such cough. Suplatast also inhibited bradykinin
      induced discharges of airway vagal afferent nerves and significantly inhibited 4
      aminopyridine-induced discharges of airway vagal afferent nerves. These findings
      indicate that the antitussive effects of suplatast are mediated by a novel
      mechanism involving the peripheral nervous system.

PMID- 25592148
TI  - Toward a science of tumor forecasting for clinical oncology.
AB  - We propose that the quantitative cancer biology community makes a concerted
      effort to apply lessons from weather forecasting to develop an analogous
      methodology for predicting and evaluating tumor growth and treatment response.
      Currently, the time course of tumor response is not predicted; instead, response
      is only assessed post hoc by physical examination or imaging methods. This
      fundamental practice within clinical oncology limits optimization of a treatment
      regimen for an individual patient, as well as to determine in real time whether
      the choice was in fact appropriate. This is especially frustrating at a time when
      a panoply of molecularly targeted therapies is available, and precision genetic
      or proteomic analyses of tumors are an established reality. By learning from the
      methods of weather and climate modeling, we submit that the forecasting power of
      biophysical and biomathematical modeling can be harnessed to hasten the arrival
      of a field of predictive oncology. With a successful methodology toward tumor
      forecasting, it should be possible to integrate large tumor-specific datasets of
      varied types and effectively defeat one cancer patient at a time.

PMID- 25592149
TI  - Establishment and characterization of a cell line from human circulating colon
      cancer cells.
AB  - Circulating tumor cells (CTC) in blood are promising new biomarkers potentially
      useful for prognostic prediction and monitoring of therapies in patients with
      solid tumors including colon cancer. Moreover, CTC research opens a new avenue
      for understanding the biology of metastasis in patients with cancer. However, an
      in-depth investigation of CTCs is hampered by the very low number of these cells,
      especially in the blood of patients with colorectal cancer. Thus, the
      establishment of cell cultures and permanent cell lines from CTCs has become the
      most challenging task over the past year. Here, we describe, for the first time,
      the establishment of cell cultures and a permanent cell line from CTCs of one
      patient with colon cancer. The cell line designated CTC-MCC-41 has been cultured
      for more than one year, and the cells have been characterized at the genome,
      transcriptome, proteome, and secretome levels. This thorough analysis showed that
      CTC-MCC-41 cells resemble characteristics of the original tumor cells in the
      patient with colon cancer and display a stable phenotype characterized by an
      intermediate epithelial/mesenchymal phenotype, stem cell-like properties, and an
      osteomimetic signature, indicating a bone marrow origin. Functional studies
      showed that CTC-MCC-41 cells induced rapidly in vitro endothelial cell tube
      formation and in vivo tumors after xenografting in immunodeficient mice. The
      establishment of this first colon cancer CTC line allows now a wealth of
      functional studies on the biology of CTCs as well as in vitro and in vivo drug
      testing.

PMID- 25592150
TI  - ERAP1 regulates natural killer cell function by controlling the engagement of
      inhibitory receptors.
AB  - The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive
      immune responses by trimming peptides for presentation by MHC class I (MHC-I)
      molecules. Herein, we demonstrate that genetic or pharmacological inhibition of
      ERAP1 on human tumor cell lines perturbs their ability to engage several classes
      of inhibitory receptors by their specific ligands, including killer cell Ig-like
      receptors (KIR) by classical MHC-I-peptide (pMHC-I) complexes and the lectin-like
      receptor CD94-NKG2A by nonclassical pMHC-I complexes, in each case leading to
      natural killer (NK) cell killing. The protective effect of pMHC-I complexes could
      be restored in ERAP1-deficient settings by the addition of known high-affinity
      peptides, suggesting that ERAP1 was needed to positively modify the affinity of
      natural ligands. Notably, ERAP1 inhibition enhanced the ability of NK cells to
      kill freshly established human lymphoblastoid cell lines from autologous or
      allogeneic sources, thereby promoting NK cytotoxic activity against target cells
      that would not be expected because of KIR-KIR ligand matching. Overall, our
      results identify ERAP1 as a modifier to leverage immune functions that may
      improve the efficacy of NK cell-based approaches for cancer immunotherapy.

PMID- 25592151
TI  - Long noncoding RNA HULC modulates abnormal lipid metabolism in hepatoma cells
      through an miR-9-mediated RXRA signaling pathway.
AB  - HULC is a long noncoding RNA overexpressed in hepatocellular carcinoma (HCC), but
      its functional contributions in this setting have not been determined. In this
      study, we explored the hypothesis that HULC contributes to malignant development
      by supporting abnormal lipid metabolism in hepatoma cells. HULC modulated the
      deregulation of lipid metabolism in HCC by activating the acyl-CoA synthetase
      subunit ACSL1. Immunohistochemical analysis of tissue microarrays revealed that
      approximately 77% (180/233) of HCC tissues were positive for ACSL1. Moreover,
      HULC mRNA levels correlated positively with ACSL1 levels in 60 HCC cases
      according to real-time PCR analysis. Mechanistic investigations showed that HULC
      upregulated the transcriptional factor PPARA, which activated the ACSL1 promoter
      in hepatoma cells. HULC also suppressed miR-9 targeting of PPARA mRNA by
      eliciting methylation of CpG islands in the miR-9 promoter. We documented the
      ability of HULC to promote lipogenesis, thereby stimulating accumulation of
      intracellular triglycerides and cholesterol in vitro and in vivo. Strikingly,
      ACSL1 overexpression that generates cholesterol was sufficient to enhance the
      proliferation of hepatoma cells. Further, cholesterol addition was sufficient to
      upregulate HULC expression through a positive feedback loop involving the
      retinoid receptor RXRA, which activated the HULC promoter. Overall, we concluded
      that HULC functions as an oncogene in hepatoma cells, acting mechanistically by
      deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA,
      and ACSL1 that is reinforced by a feed-forward pathway involving cholesterol and
      RXRA to drive HULC signaling.

PMID- 25592152
TI  - A central role for heme iron in colon carcinogenesis associated with red meat
      intake.
AB  - Epidemiology shows that red and processed meat intake is associated with an
      increased risk of colorectal cancer. Heme iron, heterocyclic amines, and
      endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but
      their relative contribution is unknown. Our study aimed at determining, at
      nutritional doses, which is the main factor involved and proposing a mechanism of
      cancer promotion by red meat. The relative part of heme iron (1% in diet),
      heterocyclic amines (PhIP + MeIQx, 50 + 25 MUg/kg in diet), and NOC (induced by
      NaNO2+ NaNO2; 0.17 + 0.23 g/L of drinking water) was determined by a factorial
      design and preneoplastic endpoints in chemically induced rats and validated on
      tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were
      analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon
      mucosa. Heme iron increased the number of preneoplastic lesions, but dietary
      heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary
      hemoglobin increased tumor load in Min mice (control diet: 67 +/- 39 mm2; 2.5%
      hemoglobin diet: 114 +/- 47 mm2, P = 0.004). In vitro, fecal water from rats
      given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not
      to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were
      more toxic to normal versus mutated cells and were only genotoxic to normal
      cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin.
      These results highlight the role of heme iron in the promotion of colon cancer by
      red meat and suggest that heme iron could initiate carcinogenesis through lipid
      peroxidation. .

PMID- 25592153
TI  - Dipeptidyl-peptidase 10 as a genetic biomarker for the aspirin-exacerbated
      respiratory disease phenotype.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an endotype of
      severe and eosinophilic adult asthma characterized by chronic rhinosinusitis with
      nasal polyps and hypersensitivity to aspirin and/or nonsteroidal anti
      inflammatory drugs. A genetic contribution of dipeptidyl-peptidase 10 (DPP10) to
      asthma susceptibility and lung function decline has been reported. However,
      little is known about the role of DPP10 in the pathogenesis of AERD. OBJECTIVE:
      To identify genetic variants of DPP10 that confer susceptibility to AERD or
      severe asthma. METHODS: A case-control association study of DPP10 gene
      polymorphisms was performed in 3 groups of patients: 274 with AERD, 272 with
      aspirin-tolerant asthma, and 99 normal healthy controls. The rs17048175 single
      nucleotide polymorphism was targeted based on a preliminary genomewide
      association study using an Affymetrix genomewide human single-nucleotide
      polymorphism array in a Korean population. DPP10, 15-hydroxyeicosatetraenoic
      acid, and YKL-40/chitinase-3-like protein were measured by enzyme-linked
      immunosorbent assay in sera taken from the study subjects. RESULTS: There was a
      significant association between rs17048175 and the AERD phenotype, but not with
      aspirin-tolerant asthma. The DPP10 level was significantly higher in sera from
      patients with AERD compared with patients with aspirin-tolerant asthma and
      control subjects (P = .021 and P < .001, respectively). In addition, there was a
      significant difference of serum DPP10 level according to the single-nucleotide
      polymorphism (P = .001). Serum DPP10 level showed a strong correlation with 15
      hydroxyeicosatetraenoic acid (r = 0.226, P = .017) and YKL-40 (r = 0.364, P =
      .004). CONCLUSION: This study suggests a genetic contribution of rs17048175 to
      DPP10 in eosinophilic inflammation induction in the airways and to AERD
      susceptibility.

PMID- 25592154
TI  - Pathology related to third molars in the elderly persons.
AB  - OBJECTIVES: The objective of this study was to clarify the discrepancy of
      pathology between earlier and recent studies related to third molars in the
      elderly persons. Evidence of third molars in the elders is limited. Earlier
      radiographic studies show rather few pathologic findings related to third molars.
      Recently, clinical studies have shown totally different numbers for pathology.
      MATERIALS AND METHODS: Participants were drawn from the population-based Helsinki
      Aging Study. The study included panoramic radiographs of 293 persons (mean age 79
      years, SD +/- 3.9 years). We examined the prevalence of third molars and
      associated pathology and used the chi-squared test to perform the statistical
      analysis. RESULTS: Of the whole group of elderly persons, 19% had at least one
      third molar. The usual dental diseases, caries and periodontal pathology (80 and
      33%, respectively), were common in the third molars. The surviving third molar
      most often appeared in the mandible (P < 0.01), in men (P < 0.05), in the
      mesioangular position (P < 0.05), and far from the mandibular canal (P < 0.001).
      Pathology was present in every third molar, although the proportion of serious
      pathology (i.e., cyst and tumor), accounted for only 2% of third molars.
      CONCLUSIONS: Although serious pathology related to third molars in the elders is
      uncommon, universal biofilm diseases (caries and periodontal pathology) widely
      affect third molars as well as all other teeth. CLINICAL RELEVANCE: Because all
      of the surviving third molars of the elders were diseased, it would be
      justifiable to extract these teeth at a younger age.

PMID- 25592155
TI  - Association of human leukocyte antigen haplotypes with clearance and persistence
      of hepatitis B virus infection in northeastern China.
AB  - This study investigated clinical implications of human leukocyte antigen (HLA) I
      and II haplotypes, in combination with HBV sub-genotype C2, in hepatitis B virus
      (HBV) infections in northeastern China. Here, HLA haplotypes of 230 HBV-infected
      patients were compared to 210 healthy, unrelated Han individuals. Of the 230 HBV
      infected patients, 54 had acute self-limited hepatitis (ASH) with sub-genotype C2
      (ASH-C2), 144 had chronic hepatitis (CH) with sub-genotypes C2 and B2 (CH-C2 and
      CH-B2), and 32 spontaneously recovered without sub-genotype results. All groups
      underwent HLA typing and haplotype analysis. The results revealed that A*02
      DRB1*12 and A*02-B*15-DRB1*09 carriers were susceptible to HBV infection. A*02
      B*15-DRB1*09 is probably associated with acute onset and viral clearance and A*02
      DRB1*12, with viral persistence. In HBV infections, B*40-DRB1*12 was associated
      with HBV persistence, whereas B*46-DRB1*09, A*24-DRB1*14, and B*15-DRB1*04
      carriers easily recovered from the disease. By contrast, when infected with the
      HBV-C2 sub-genotype, A*24-DRB1*14, B*15-DRB1*04, A*02-B*15, A*02-DRB1*15, and
      A*02-B*15-DRB1*09 carriers displayed an acute clinical course before recovery.
      This study reveals a relationship between HLA haplotypes and HBV pathogenesis,
      thereby providing potential therapeutic targets to treat HBV infection. 

PMID- 25592156
TI  - Characterization of molecular transport in ultrathin hydrogel coatings for
      cellular immunoprotection.
AB  - PEG hydrogels are routinely used in immunoprotection applications to hide foreign
      cells from a host immune system. Size-dependent transport is typically exploited
      in these systems to prevent access by macromolecular elements of the immune
      system while allowing the transport of low molecular weight nutrients. This work
      studies a nanoscale hydrogel coating for improved transport of beneficial low
      molecular weight materials across thicker hydrogel coatings while completely
      blocking transport of undesired larger molecular weight materials. Coatings
      composed of PEG diacrylate of molecular weight 575 and 3500 Da were studied by
      tracking the transport of fluorescently labeled dextrans across the coatings. The
      molecular weight of dextran at which the transport is blocked by these coatings
      are consistent with cutoff values in analogous bulk PEG materials. Additionally,
      the diffusion constants of 4 kDa dextrans across PEG 575 coatings (9.5 * 10(-10)
      2.0 * 10(-9) cm(2)/s) was lower than across PEG 3500 coatings (5.9-9.8 * 10(-9)
      cm(2)/s), and these trends and magnitudes agree with bulk scale models. Overall,
      these nanoscale thin PEG diacrylate films offer the same size selective transport
      behavior of bulk PEG diacrylate materials, while the lower thickness translates
      directly to increased flux of beneficial low molecular weight materials. 

PMID- 25592157
TI  - Reduced susceptibility to induced seizures in the Neuroligin-3(R451C) mouse model
      of autism.
AB  - Epilepsy is a common comorbidity in patients with autism spectrum disorder (ASD)
      and several gene mutations are associated with both of these disorders. In order
      to determine whether a point mutation in the gene for the synaptic protein,
      Neuroligin-3 (Nlgn3, R451C), identified in patients with ASD alters seizure
      susceptibility, we administered the proconvulsant pentylenetetrazole (PTZ) to
      adult male Neuroligin-3(R451C) (NL3(R451C)) and wild type (WT) mice. It has
      previously been reported that NL3(R451C) mice show altered inhibitory GABAergic
      activity in brain regions relevant to epilepsy, including the hippocampus and
      somatosensory cortex. PTZ administration induces absence-seizures at low dose,
      and generalised convulsive seizures at higher dose. Susceptibility to absence
      seizures was examined by analysing the frequency and duration of spike-and-wave
      discharge (SWD) events and accompanying motor seizure activity induced by
      subcutaneous administration of low dosage (20 or 30mg/kg) PTZ. Susceptibility to
      generalised convulsive seizures was tested by measuring the response to high
      dosage (60mg/kg) PTZ using a modified Racine scale. There was no change in the
      number of SWD events exhibited by NL3(R451C) compared to WT mice following
      administration of both 20mg/kg PTZ (1.17+/-0.31 compared to 16.0+/-11.16
      events/30min, NL3(R451C) versus WT, respectively) and 30mg/kg PTZ (7.5+/-6.54
      compared with 27.8+/-19.9 events/30min, NL3(R451C) versus WT, respectively).
      NL3(R451C) mice were seizure resistant to generalised convulsive seizures induced
      by high dose PTZ compared to WT littermates (median latency to first >3s duration
      clonic seizure; 14.5min versus 7.25min, 95% CI: 1.625-2.375, p=0.0009, NL3(R451C)
      versus WT, respectively). These results indicate that the R451C mutation in the
      Nlgn3 gene, associated with ASD in humans, confers resistance to induced
      seizures, suggesting dysfunction of PTZ-sensitive GABAergic signalling in this
      mouse model of ASD. 

PMID- 25592158
TI  - Micro-elastometry on whole blood clots using actuated surface-attached posts
      (ASAPs).
AB  - We present a novel technology for microfluidic elastometry and demonstrate its
      ability to measure stiffness of blood clots as they form. A disposable micro
      capillary strip draws small volumes (20 MUL) of whole blood into a chamber
      containing a surface-mounted micropost array. The posts are magnetically
      actuated, thereby applying a shear stress to the blood clot. The posts' response
      to magnetic field changes as the blood clot forms; this response is measured by
      optical transmission. We show that a quasi-static model correctly predicts the
      torque applied to the microposts. We experimentally validate the ability of the
      system to measure clot stiffness by correlating our system with a commercial
      thromboelastograph. We conclude that actuated surface-attached post (ASAP)
      technology addresses a clinical need for point-of-care and small-volume elastic
      haemostatic assays. 

PMID- 25592160
TI  - Do people with and without medical conditions respond similarly to the short
      health anxiety inventory? An assessment of differential item functioning using
      item response theory.
AB  - OBJECTIVE: Individuals with medical conditions are likely to have elevated health
      anxiety; however, research has not demonstrated how medical status impacts
      response patterns on health anxiety measures. Measurement bias can undermine the
      validity of a questionnaire by overestimating or underestimating scores in groups
      of individuals. We investigated whether the Short Health Anxiety Inventory
      (SHAI), a widely-used measure of health anxiety, exhibits medical condition-based
      bias on item and subscale levels, and whether the SHAI subscales adequately
      assess the health anxiety continuum. METHODS: Data were from 963 individuals with
      diabetes, breast cancer, or multiple sclerosis, and 372 healthy individuals.
      Mantel-Haenszel tests and item characteristic curves were used to classify the
      severity of item-level differential item functioning in all three medical groups
      compared to the healthy group. Test characteristic curves were used to assess
      scale-level differential item functioning and whether the SHAI subscales
      adequately assess the health anxiety continuum. RESULTS: Nine out of 14 items
      exhibited differential item functioning. Two items exhibited differential item
      functioning in all medical groups compared to the healthy group. In both Thought
      Intrusion and Fear of Illness subscales, differential item functioning was
      associated with mildly deflated scores in medical groups with very high levels of
      the latent traits. Fear of Illness items poorly discriminated between individuals
      with low and very low levels of the latent trait. CONCLUSIONS: While individuals
      with medical conditions may respond differentially to some items, clinicians and
      researchers can confidently use the SHAI with a variety of medical populations
      without concern of significant bias.

PMID- 25592159
TI  - Electronic protocol for suicide risk management in research participants.
AB  - OBJECTIVE: To describe an electronic, telephone-delivered, suicide risk
      management protocol (SRMP) that is designed to guide research staff and safely
      triage study participants who are at risk for self-harm. METHODS: We tested the
      SRMP in the context of the NIH-funded randomized clinical trial "Bypassing the
      Blues" in which 302 patients who had undergone coronary artery bypass graft
      surgery (CABG) were screened for depression and assessed by telephone 2-weeks
      following hospital discharge and at 2-, 4-, and 8-month follow-up. We programmed
      the SRMP to assign different risk levels based on patients' answers from none to
      imminent with action items for research staff keyed to each of them. We describe
      frequency of suicidal thinking, SRMP use, and completion of specific steps in the
      SRMP management process over the 8-month follow-up period. RESULTS: Suicidal
      ideation was expressed by 74 (25%) of the 302 study participants in 139 (13%) of
      the 1069 blinded telephone assessments performed by research staff. The SRMP was
      launched in 103 (10%) of assessments, and the suicidal risk level was classified
      as moderate or high in 10 (1%) of these assessments, thereby necessitating an
      immediate evaluation by a study psychiatrist. However, no hospitalizations,
      emergency room visits, or deaths ascribed to suicidal ideation were discovered
      during the study period. CONCLUSION: The SRMP was successful in systematically
      and safely guiding research staff lacking specialty mental health training
      through the standardized risk assessment and triaging research participants at
      risk for self-harm. TRIAL REGISTRATION: Clinicaltrials.gov Identifier:
      NCT00091962
      (http://clinicaltrials.gov/ct2/show/NCT00091962?term=rollman+cabg&rank=1).

PMID- 25592161
TI  - Relationships between adult attachment style ratings and sleep disturbances in a
      nationally representative sample.
AB  - OBJECTIVE: Recent research with small non-clinical and clinical samples suggests
      a positive association between attachment insecurity and sleep disturbances. The
      present study extends this line of research by exploring this relationship in a
      large sample of the U.S. population and by statistically adjusting for health
      conditions and psychiatric disorders as potential confounds. METHOD: The data
      used were from the National Comorbidity Survey Replication (N=5692). The main
      interview consisted of the Composite International Diagnostic Interview used to
      assess psychiatric diagnoses. Ratings of three adult attachment styles (viz.,
      secure, avoidant, and anxious) were obtained along with self-reports of health
      conditions and four sleep disturbances (viz., difficulty initiating sleep,
      difficulty maintaining sleep, early morning awakening, and daytime sleepiness).
      RESULTS: Bivariate logistic regression analyses indicated that ratings of secure
      attachment were negatively associated with each sleep disturbance and ratings of
      insecure attachment were positively associated with each sleep disturbance.
      Multivariate logistic regression analyses were used to examine associations
      between the attachment ratings and sleep disturbances while statistically
      controlling for sociodemographic variables, the presence of a health condition,
      and psychiatric disorders (viz., depressive disorders, bipolar disorders, anxiety
      disorders, alcohol/substance disorders, and attention deficit disorder). With one
      exception, the insecure attachment ratings continued to be positively associated
      with sleep disturbances. CONCLUSION: The findings demonstrate that attachment
      insecurity is related to sleep disturbances independent of health conditions and
      concurrent psychiatric disorders. Research aimed at delineating the mechanisms
      responsible for these associations is warranted.

PMID- 25592162
TI  - Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing
      cytochrome p450 2E1 induction in rodent models.
AB  - Chronic and excessive alcohol consumption leads to the development of alcoholic
      liver disease (ALD) and greatly increases the risk of liver cancer. Induction of
      the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake
      is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich
      in the carotenoid lycopene, is associated with a decreased risk of chronic
      disease. We investigated the effects of whole tomato (tomato powder, TP), partial
      tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development
      in rats. Of the three supplements, only TP reduced the severity of alcohol
      induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had
      no effect on these outcomes and LYC greatly increased inflammatory foci in
      alcohol-fed rats. To further support the protective effect of TP against ALD, TP
      was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol
      promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP
      abolished the presence of preneoplastic foci of altered hepatocytes in DEN
      injected mice fed alcohol. These reductions were associated with decreased
      hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator
      activated receptor-alpha and downstream gene expression, decreased inflammatory
      gene expression, and reduced endoplasmic reticulum stress markers. These data
      provide strong evidence for TP as an effective whole food prevention strategy
      against ALD.

PMID- 25592163
TI  - Leadership and organizational change for implementation (LOCI): a randomized
      mixed method pilot study of a leadership and organization development
      intervention for evidence-based practice implementation.
AB  - BACKGROUND: Leadership is important in the implementation of innovation in
      business, health, and allied health care settings. Yet there is a need for
      empirically validated organizational interventions for coordinated leadership and
      organizational development strategies to facilitate effective evidence-based
      practice (EBP) implementation. This paper describes the initial feasibility,
      acceptability, and perceived utility of the Leadership and Organizational Change
      for Implementation (LOCI) intervention. A transdisciplinary team of investigators
      and community stakeholders worked together to develop and test a leadership and
      organizational strategy to promote effective leadership for implementing EBPs.
      METHODS: Participants were 12 mental health service team leaders and their staff
      (n = 100) from three different agencies that provide mental health services to
      children and families in California, USA. Supervisors were randomly assigned to
      the 6-month LOCI intervention or to a two-session leadership webinar control
      condition provided by a well-known leadership training organization. We utilized
      mixed methods with quantitative surveys and qualitative data collected via
      surveys and a focus group with LOCI trainees. RESULTS: Quantitative and
      qualitative analyses support the LOCI training and organizational strategy
      intervention in regard to feasibility, acceptability, and perceived utility, as
      well as impact on leader and supervisee-rated outcomes. CONCLUSIONS: The LOCI
      leadership and organizational change for implementation intervention is a
      feasible and acceptable strategy that has utility to improve staff-rated
      leadership for EBP implementation. Further studies are needed to conduct rigorous
      tests of the proximal and distal impacts of LOCI on leader behaviors,
      implementation leadership, organizational context, and implementation outcomes.
      The results of this study suggest that LOCI may be a viable strategy to support
      organizations in preparing for the implementation and sustainment of EBP.

PMID- 25592164
TI  - Gene expression profiling analysis of castration-resistant prostate cancer.
AB  - BACKGROUND: Prostate cancer is a global health issue. Usually, men with
      metastatic disease will progress to castration-resistant prostate cancer (CRPC).
      We aimed to identify the differentially expressed genes (DEGs) in tumor samples
      from non-castrated and castrated men from LNCaP Orthotopic xenograft models of
      prostate cancer and to study the mechanisms of CRPC. MATERIAL/METHODS: In this
      work, GSE46218 containing 4 samples from non-castrated men and 4 samples from
      castrated men was downloaded from Gene Expression Omnibus. We identified DEGs
      using limma Geoquery in R, the Robust Multi-array Average (RMA) method in
      Bioconductor, and Bias methods, followed by constructing an integrated regulatory
      network involving DEGs, miRNAs, and TFs using Cytoscape. Then, we analyzed
      network motifs of the integrated gene regulatory network using FANMOD. We
      selected regulatory modules corresponding to network motifs from the integrated
      regulatory network by Perl script. We preformed gene ontology (GO) and pathway
      enrichment analysis of DEGs in the regulatory modules using DAVID. RESULTS: We
      identified total 443 DEGs. We built an integrated regulatory network, found three
      motifs (motif 1, motif 2 and motif 3), and got two function modules (module 1
      corresponded to motif 1, and module 2 corresponded to motif 2). Several GO terms
      (such as regulation of cell proliferation, positive regulation of macromolecule
      metabolic process, phosphorylation, and phosphorus metabolic process) and two
      pathways (pathway in cancer and Melanoma) were enriched. Furthermore, some
      significant DEGs (such as CAV1, LYN, FGFR3 and FGFR3) were related to CPRC
      development. CONCLUSIONS: These genes might play important roles in the
      development and progression of CRPC.

PMID- 25592165
TI  - The resistible rise of B-line lung ultrasound artefacts.

PMID- 25592166
TI  - The impact of patients' involvement in cooking on their mortality and morbidity:
      a 19-year follow-up of patients diagnosed with type 2 diabetes mellitus.
AB  - OBJECTIVE: This study explored the impact of involvement in cooking on long-term
      morbidity and mortality among patients newly diagnosed with type 2 diabetes
      mellitus (T2DM). DESIGN AND SUBJECTS: Data are from the population-based study
      Diabetes Care in General Practice. In baseline questionnaires, 1348 patients
      newly diagnosed with T2DM gave information on how frequently they consumed a warm
      main meal and how often they cooked it themselves. The selected patients were
      followed up for 19 years in the Danish National Patient Registry and the Danish
      Register of Causes of Death. MAIN OUTCOME MEASURES: This study analysed the
      association between involvement in cooking and each of seven pre-specified
      outcomes was analysed in Cox regression models with stepwise adjustment for
      possible confounders and mediators. RESULTS: 92% of the patients with T2DM
      consumed a warm main meal >= five times per week. Among these, women who cooked
      for themselves less than once a week had a higher risk of diabetes-related deaths
      (HR 1.86 [95% CI 1.03-3.35], p = 0.039) and stroke (HR 2.47 [95% CI 1.08-5.65], p
      = 0.033), after adjustment for confounders. For men, infrequent cooking was not
      related to increased risk for the outcomes investigated. CONCLUSIONS: In patients
      newly diagnosed with T2DM and with a regular intake of warm main meals,
      infrequent involvement in cooking was associated with an increased risk of
      diabetes-related death and stroke for women, but not for men. General
      practitioners should pay special attention to managing diabetes treatment in
      female patients newly diagnosed with T2DM who report infrequent involvement in
      cooking.

PMID- 25592168
TI  - Amiloride inhibits osteoclastogenesis by suppressing nuclear factor-kappaB and
      mitogen-activated protein kinase activity in receptor activator of nuclear factor
      kappaB-induced RAW264.7 cells.
AB  - Amiloride is widely used in clinical practice as a diuretic and is known to
      interact with the epithelial sodium channel and acid-sensing ion channel
      proteins, as well as Na+/H+ antiporters and Na+/Ca2+ exchangers. The aim of the
      present study was to examine the effects of amiloride on receptor activator of
      nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis and to elucidate
      the underlying mechanisms in the RAW264.7 murine macrophage cell line. The number
      of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were
      counted and the bone resorption area was estimated. In addition the expression
      levels of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) mRNA and
      osteoclast-specific genes, including TRAP, matrix metalloproteinase 9, cathepsin
      K and osteoclast-associated receptor, were examined using reverse transcription
      quantitative polymerase chain reaction. The nuclear factor-kappaB (NF-kappaB) and
      mitogen-activated protein kinase (MAPK) signaling pathways were also investigated
      using western blotting. The results showed that amiloride significantly reduced
      the number of TRAP-positive multinucleated cells as well as the bone resorption
      area. Amiloride also downregulated the expression of NFATc1 mRNA and inhibited
      the expression of osteoclast-specific genes. A possible underlying mechanism may
      be that amiloride suppresses the degradation of the inhibitor of NF-kappaB and
      blocks the activation of c-Jun N-terminal kinase, extracellular signal-regulated
      kinase and p38, thus implicating the NF-kappaB and MAPK pathway is this process.
      In conclusion, the current data suggest that amiloride is a strong inhibitor of
      osteoclast differentiation, indicating a novel indication for amiloride in the
      treatment of bone-loss-related diseases.

PMID- 25592169
TI  - Adjustment for compliance behavior in trials of epidural analgesia in labor using
      instrumental variable meta-analysis.
AB  - OBJECTIVES: Intention-to-treat (ITT) analysis of randomized controlled trials
      (RCTs) may cause bias when compliance is poor. Noncompliance describes failure to
      comply with allocation in the intervention arm, and contamination describes
      uptake of the intervention in the control arm. Instrumental variable (IV)
      analysis can be applied in addition to the primary ITT analysis to estimate the
      causal effect adjusted for noncompliance and contamination, assuming that
      noncompliers would have had the same treatment benefit as compliers. We aimed to
      compare ITT and IV meta-analysis of the association between epidural analgesia in
      labor and cesarean section. STUDY DESIGN AND SETTING: The study was restricted to
      27 trials in a Cochrane Systematic Review. The association between epidural
      analgesia in labor and cesarean section was calculated using ITT and IV analyses.
      Pooled risk ratios (RRs) were calculated using fixed-effects meta-analysis.
      RESULTS: In 18 trials with compliance data, noncompliance was 23% and
      contamination was 27%. In 10 trials with outcome data stratified by compliance,
      the pooled RR for cesarean section following epidural analgesia was 1.37 [95%
      confidence interval (CI): 1.00, 1.89; P = 0.049] using IV compared with 1.19 (95%
      CI: 0.93, 1.51; P = 0.16) using ITT. CONCLUSION: ITT meta-analysis underestimates
      the effect of receiving epidural analgesia in labor on cesarean section compared
      with IV meta-analysis.

PMID- 25592170
TI  - Using the numerical method in 1836, James Jackson bridged French therapeutic
      epistemology and American medical pragmatism.
AB  - OBJECTIVES: To review James Jackson's analysis of bloodletting among pneumonitis
      patients at the newly founded Massachusetts General Hospital, in which he
      implemented the numerical method advocated by Pierre-Charles-Alexandre Louis.
      STUDY DESIGN AND SETTING: The study sample included 34 cases of clinically
      diagnosed pneumonitis admitted to Massachusetts General Hospital between April
      19, 1825, and May 10, 1835, and discharged alive. Patient data were extracted
      from meticulously kept case books. Jackson calculated mean number of
      venesections, ounces of blood taken, and days of convalescence within groups
      stratified by day of the disease when first bloodletting occurred. He also
      calculated average convalescence within groups stratified by age, sex, prior
      health, vesication, and day of the disease when the patients were admitted to the
      hospital. RESULTS: To Jackson's surprise, it "seemed to be of less importance,
      whether our patients were bled or not, than whether they entered the hospital
      early or late" after the onset of the pneumonitis. Bloodletting was ineffective.
      Our multivariate reanalysis of his data confirms his conclusion. Outstandingly
      for his time, Jackson ruled out unwarranted effects of covariates by tabulating
      their numerical relations to the duration of pneumonia. CONCLUSION: Using novel
      gathering of patient clinical data from hospital records and quantitative
      analytical methods, Jackson contributed results that challenged conventional
      wisdom and bridged French therapeutic epistemology and American medical
      pragmatism.

PMID- 25592171
TI  - Estimating the endotracheal tube insertion depth in newborns using weight or
      gestation: a randomised trial.
AB  - BACKGROUND: When intubating newborns, clinicians aim to place the tip of the
      endotracheal tube (ETT) in the mid-trachea. Clinicians usually estimate the ETT
      insertion depth based on weight. ETT tips are often incorrectly positioned in
      newborns. Estimating the insertion depth based on gestation may be more accurate.
      OBJECTIVE: To determine whether estimating the ETT insertion depth using
      gestation, compared to weight, results in more correctly placed ETTs. METHODS:
      Newborn infants without congenital anomalies who were intubated orally were
      randomised to having their ETT insertion depth estimated using weight [insertion
      depth (cm) = weight (kg) + 6] or gestation [value determined from a table]. The
      primary outcome was correct ETT position, defined as an ETT tip between the upper
      border of the first thoracic vertebra (T1) and the lower border of the second
      thoracic vertebra (T2) on a chest X-ray. The primary outcome was determined by
      one paediatric radiologist who was masked to group assignment. RESULTS: Ninety
      infants were enrolled and the groups were well matched. The proportion of
      correctly placed ETTs was not significantly different between the groups [weight,
      25/49 (51%), vs. gestation, 16/41 (39%), p = 0.293]. We found no significant
      differences in the secondary outcomes measured. CONCLUSION: Estimating the ETT
      insertion depth in newborns using gestation compared to weight did not result in
      more correctly placed ETTs.

PMID- 25592172
TI  - Reintubation in critically ill patients: procedural complications and
      implications for care.
AB  - INTRODUCTION: In critically ill patients, re-intubation is common and may be a
      high-risk procedure. Anticipating a difficult airway and identifying high-risk
      patients can allow time for life-saving preparation. Unfortunately, prospective
      studies have not compared the difficulty or complication rates associated with
      reintubation in this population. METHODS: We performed a secondary analysis of a
      prospective registry of in-hospital emergency airway management, focusing on
      patients that underwent multiple out-of-operating room intubations during a
      single hospitalization. Our main outcomes of interest were technical difficulty
      of intubation (number of attempts, need for adjuncts to direct laryngoscopy, best
      Cormack-Lehane grade and training level of final intubator) and the frequency of
      procedural complications (aspiration, arrhythmia, airway trauma, new hypotension,
      new hypoxia, esophageal intubation and cardiac arrest). We compared the cohort of
      reintubated patients to a matched cohort of singly intubated patients and
      compared each repeatedly intubated patient's first and last intubation. RESULTS:
      Our registry included 1053 patients, of which 151 patients (14%) were repeatedly
      intubated (median two per patient). Complications were significantly more common
      during last intubation compared to first (13% versus 5%, P = 0.02). The most
      common complications were hypotension (41%) and hypoxia (35%). These occurred
      despite no difference in any measure of technical difficultly across intubations.
      CONCLUSION: In this cohort of reintubated patients, clinically important
      procedural complications were significantly more common on last intubation
      compared to first.

PMID- 25592174
TI  - Plasmonically sensitized metal-oxide electron extraction layers for organic solar
      cells.
AB  - ZnO and TiOx are commonly used as electron extraction layers (EELs) in organic
      solar cells (OSCs). A general phenomenon of OSCs incorporating these metal-oxides
      is the requirement to illuminate the devices with UV light in order to improve
      device characteristics. This may cause severe problems if UV to VIS down
      conversion is applied or if the UV spectral range (lambda < 400 nm) is blocked to
      achieve an improved device lifetime. In this work, silver nanoparticles (AgNP)
      are used to plasmonically sensitize metal-oxide based EELs in the vicinity (1-20
      nm) of the metal-oxide/organic interface. We evidence that plasmonically
      sensitized metal-oxide layers facilitate electron extraction and afford well
      behaved highly efficient OSCs, even without the typical requirement of UV
      exposure. It is shown that in the plasmonically sensitized metal-oxides the
      illumination with visible light lowers the WF due to desorption of previously
      ionosorbed oxygen, in analogy to the process found in neat metal oxides upon UV
      exposure, only. As underlying mechanism the transfer of hot holes from the metal
      to the oxide upon illumination with hnu < Eg is verified. The general
      applicability of this concept to most common metal-oxides (e.g. TiOx and ZnO) in
      combination with different photoactive organic materials is demonstrated.

PMID- 25592173
TI  - Systematical analyses of variants in CTCF-binding sites identified a novel lung
      cancer susceptibility locus among Chinese population.
AB  - Genome-wide association studies identified genetic susceptibility variants mostly
      lie outside of protein-coding regions. It suggested variants located at
      transcriptional regulatory region should play an important role in cancer
      carcinogenesis including lung cancer. In the present study, we systematically
      investigated the associations between the variants in the binding sites of an
      extensive transcription factor CTCF and lung cancer risk in Chinese population. A
      two-stage case-control design was conducted to evaluate the variants located at
      the uniform CTCF ChIP-seq peaks in a Chinese population (2,331 vs 3,077; 1,115 vs
      1,346). The ChIP-seq data for CTCF, specified on lung cancer cell line A549, were
      downloaded from ENCODE database. Imputation was performed to increase the genome
      coverage in the CTCF binding regions. Three variants in CTCF binding sites were
      found to associate with lung cancer risk in the first stage. Further replication
      revealed a novel single nucleotide polymorphism rs60507107 was significantly
      associated with increased risk of lung cancer in two stages (Additive model: OR =
      1.19, 95%CI = 1.11-1.27, P = 6.98 * 10(-7)). Our results indicate that rs60507107
      in the binding site of CTCF is associated with an increased risk of lung cancer.
      This may further advance our understanding of regulatory DNA sequences in cancer
      development.

PMID- 25592175
TI  - Predicting fatigue in older breast cancer patients receiving radiotherapy. A head
      to-head comparison of established assessments.
AB  - OBJECTIVES: Because of substantial toxicities in older adults, chemotherapy is
      often omitted while the frequency of radiotherapy changes only minimally. In this
      study, we addressed the value of different assessments for predicting fatigue
      after radiotherapy in older breast cancer patients. PATIENTS AND METHODS: We
      included 74 women with primary breast cancer over the age of 65 years treated
      with radiotherapy (26 % with additional chemotherapy). Assessments were conducted
      before adjuvant treatment and after radiotherapy. The assessments included the
      Vulnerable Elders Survey (VES-13), the Karnofsky Performance Status (KPS), the
      EORTC Quality of Life assessment (EORTC-QLQ-C30), a cancer-specific comprehensive
      geriatric assessment (cancer-specific CGA), and the Fried frailty score. Multiple
      linear regression analyses were used to assess correlations with the FACIT
      fatigue scale. RESULTS: Patients were on average 71 years old (range, 65-86
      years). Most tumors (n=62) were classified as intermediate risk according to the
      St. Gallen consensus. The cancer-specific CGA was best associated with fatigue (p
      < 0.001, beta estimate = 1.75), followed by the Fried frailty score (for the
      score of 1 versus reference of 2 and higher: p = 0.035, beta estimate = - 5.74).
      There were no significant ceiling effects but there were substantial floor
      effects for the VES-13, KPS, and frailty score. CONCLUSION: The cancer-specific
      CGA and the Fried frailty score (driven mainly by the item "exhaustion")
      outperformed the other indices in predicting fatigue in a group of rather well
      functioning older women with primary breast cancer.

PMID- 25592176
TI  - Parameters of bone health and fracture risk in older female fall victims: what do
      they tell us?
AB  - INTRODUCTION: A common and severe osteoporotic type fracture in older women is a
      hip fracture. It is not clear whether bone turnover parameters measured in blood
      can be a useful tool to predict fracture risk in older persons. The aim of the
      current study was to assess the association between serum vitamin D (25OHD)
      levels, parathyroid hormone (PTH), total osteocalcin, carboxy-terminal collagen
      crosslinks (CTX) and hip fractures in older fallers. MATERIAL AND METHODS: A
      single centre, prospective cohort study of bone parameters was carried out in 400
      female patients aged > 70 years including 200 with a hip fracture and 200 without
      fractures, admitted after a fall between January 2005 and December 2007. RESULTS:
      Serum total osteocalcin levels were significantly lower in the fracture group
      compared to the non-fracture group (20.4 ng/ml vs 26.1 ng/ml, respectively, p =
      0.01). This finding remained significant after exclusion of the patients on
      bisphosphonates (p = 0.003). There were no significant differences in 25OHD, PTH
      or CTX levels between the two groups. CONCLUSION: In the current study there was
      an association between the presence of a hip fracture and lower total serum
      osteocalcin concentrations. This could be indicative of low bone turnover
      osteoporosis in these women. An association for other bone turnover markers was
      lacking.

PMID- 25592177
TI  - Instruments to identify elderly patients in the emergency department in need of
      geriatric care.
AB  - The number of people with functional limitations, cognitive impairment and
      disability with unscheduled, unintended contact to emergency departments seeking
      acute medical care is increasing. With this, the problem of how to identify
      elderly people in need for acute geriatric care has evolved. The best solution to
      the problem would be to perform comprehensive geriatric assessment during the
      initial contact; however, comprehensive geriatric assessment is considered too
      complex and therefore not feasible for emergency departments. Instead, screening
      instruments have been developed and proposed. In this narrative review, selected
      screening instruments are discussed. The instrument best studied in various
      settings and countries is the Identification of Seniors At Risk (ISAR) screening
      tool which contains six simple questions that are easy to administer and can be
      assessed even in urgent situations. In recent years, several studies have
      examined the validity of ISAR in different European countries. Most of these
      studies, including one German study and a recent systematic review, confirmed the
      validity of ISAR. Unfortunately, evidence is conflicting, as some studies found
      only weak or even no association between ISAR and negative health outcomes. Other
      instruments have been investigated to a lesser extent and do not indicate obvious
      advantages over ISAR. Despite growing evidence in the field, there are still many
      uncertainties. Further research is needed to solve existing inconsistencies and
      to assess how elderly patients screened positive for acute geriatric care needs
      can best be managed further. 

PMID- 25592179
TI  - Meet the new Hormones and Cancer editorial team: Donald P. McDonnell, Associate
      Editor.

PMID- 25592178
TI  - [Systolic heart failure in elderly patients].
AB  - Heart failure is becoming more and more important because of an increasing
      prevalence in elderly people. Even in healthy elderly individuals there are
      physiological changes in the cardiovascular system which can be modified by
      cardiac risk factors and comorbidities and trigger the onset of heart failure.
      The symptoms in the elderly are often atypical and can be difficult to diagnose
      in the presence of comorbidities. Echocardiography is important for the diagnosis
      of heart failure and can be easily and non-invasively performed. This can be
      complemented by further imaging methods and serological tests, such as
      determination of the concentrations of brain natriuretic peptide (BNP) and n
      terminal pro-brain natriuretic peptide (NTproBNP). In elderly patients the
      problem of polypharmacy often arises. Therapeutic goals are in particular
      improvement in the quality of life and of symptoms. 

PMID- 25592180
TI  - Meet the new Hormones and Cancer editorial team: Nancy L. Weigel, Editor-in
      Chief.

PMID- 25592181
TI  - A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in
      plants.
AB  - Activated forms of jasmonic acid (JA) are central signals coordinating plant
      responses to stresses, yet tools to analyse their spatial and temporal
      distribution are lacking. Here we describe a JA perception biosensor termed Jas9
      VENUS that allows the quantification of dynamic changes in JA distribution in
      response to stress with high spatiotemporal sensitivity. We show that Jas9-VENUS
      abundance is dependent on bioactive JA isoforms, the COI1 co-receptor, a
      functional Jas motif and proteasome activity. We demonstrate the utility of Jas9
      VENUS to analyse responses to JA in planta at a cellular scale, both
      quantitatively and dynamically. This included using Jas9-VENUS to determine the
      cotyledon-to-root JA signal velocities on wounding, revealing two distinct phases
      of JA activity in the root. Our results demonstrate the value of developing
      quantitative sensors such as Jas9-VENUS to provide high-resolution spatiotemporal
      data about hormone distribution in response to plant abiotic and biotic stresses.

PMID- 25592183
TI  - Robust resting state fMRI processing for studies on typical brain development
      based on multi-echo EPI acquisition.
AB  - Several methodological challenges affect the study of typical brain development
      based on resting state blood oxygenation level dependent (BOLD) functional MRI
      (fMRI). One such challenge is mitigating artifacts such as those from head
      motion, known to be more substantial in younger subjects than older subjects.
      Other challenges include controlling for potential age-dependence in
      cerebrospinal fluid (CSF) volume affecting anatomical-functional coregistration;
      in vascular density affecting BOLD contrast-to-noise; and in CSF pulsation
      creating time series artifacts. Historically, these confounds have been
      approached through incorporating artifact-specific temporal and/or spatial
      filtering into preprocessing pipelines. However, such paths often come with new
      confounds or limitations. In this study we take the approach of a bottom-up
      revision of fMRI methodology based on acquisition of multi-echo fMRI and
      comprehensive utilization of the information in the TE-domain to enhance several
      aspects of fMRI analysis in the context of a developmental study. We show in a
      cohort of 25 healthy subjects, aged 9 to 43 years, that the analysis of multi
      echo fMRI data eliminates a number of arbitrary processing steps such as bandpass
      filtering and spatial smoothing, while enabling procedures such as [Formula: see
      text] mapping, BOLD contrast normalization and signal dropout recovery, precise
      anatomical-functional coregistration based on [Formula: see text] measurements,
      automatic denoising through removing subject motion, scanner-related signal
      drifts and physiology, as well as statistical inference for seed-based
      connectivity. These enhancements are of both theoretical significance and
      practical benefit in the study of typical brain development. 

PMID- 25592182
TI  - Release from incarceration, relapse to opioid use and the potential for
      buprenorphine maintenance treatment: a qualitative study of the perceptions of
      former inmates with opioid use disorder.
AB  - BACKGROUND: The United States has the highest rate of incarceration in the world
      (937 per 100,000 adults). Approximately one-third of heroin users pass through
      correctional facilities annually. Few receive medication assisted treatment (MAT;
      either methadone or buprenorphine) for opioid use disorder during incarceration,
      and nearly three-quarters relapse to heroin use within 3 months of release. This
      qualitative study investigated barriers to and facilitators of buprenorphine
      maintenance treatment (BMT) following release from incarceration ("re-entry").
      METHODS: We conducted 21 semistructured interviews of former inmates with opioid
      use disorder recruited from addiction treatment settings. Interviews were audio
      recorded, transcribed, and analyzed using a grounded theory approach. Themes that
      emerged upon iterative readings of transcripts were discussed by the research
      team. RESULTS: Participants reported adverse re-entry conditions, including
      persistent exposure to drug use and stressful life events, which were perceived
      to contribute to opioid relapse and affected addiction treatment decisions during
      re-entry. Themes that emerged relating to BMT included: 1) reliance on willpower;
      2) fear of dependency on medications; 3) variable exposure to buprenorphine; and
      4) acceptability of BMT following relapse. Willpower was perceived to be more
      important for recovery than medications. Many participants experienced painful
      withdrawal from methadone during incarceration and were fearful that using MAT
      would lead to opioid tolerance and painful withdrawal again in the future.
      Participants reported both positive and negative experiences taking illicit
      buprenorphine, which affected interest in BMT. Overall, BMT was perceived to be a
      good treatment option for opioid use disorder that could reduce the risk of re
      incarceration. CONCLUSIONS: BMT was perceived to be acceptable, but former
      inmates with opioid use disorder may be reluctant to utilize BMT upon re-entry.
      Factors limiting utilization of BMT could be mitigated though policy change or
      interventions. Policies of the criminal justice system (e.g., forced
      detoxification) may be dissuading former inmates from utilizing effective
      treatments for opioid use disorder. Interventions that improve education and
      access to BMT for former inmates with opioid use disorder could facilitate
      entrance into treatment. Both policy changes and interventions are urgently
      needed to reduce the negative consequences of opioid relapse following re-entry.

PMID- 25592184
TI  - Drying-induced cavitation in a constrained hydrogel.
AB  - Cavitation can be often observed in soft materials. Most previous studies were
      focused on cavitation in an elastomer, which is under different mechanical
      loadings. In this paper, we investigate cavitation in a constrained hydrogel
      induced by drying. Taking account of surface tension and chemo-mechanics of gels,
      we calculate the free energy of the system as a function of cavity size. The free
      energy landscape shows a double-well structure, analogous to first-order phase
      transition. Above the critical humidity, a cavity inside the gel is tiny. Below
      the critical humidity, the size of the cavity is large. At the critical humidity,
      the cavity size grows suddenly and discontinuously. We further show that local
      large stretches can be induced in the gel during the drying process, which may
      result in fractures. 

PMID- 25592186
TI  - Tension of the ulnar, median, and radial nerves during ulnar nerve neurodynamic
      testing: observational cadaveric study.
AB  - BACKGROUND: The ulnar nerve upper limb neurodynamic test (ULNT3) uses upper limb
      positioning to investigate symptoms arising from the ulnar nerve. It is proposed
      to selectively increase tension of the nerve; however, this property of the test
      is not well established. OBJECTIVE: The aim of this study was to determine the
      upper limb position that results in: (1) the greatest tension of the ulnar nerve
      and (2) the greatest difference in tension between the ulnar nerve and the other
      2 major nerves of the upper limb: median and radial. DESIGN: This was an
      observational cadaver study. METHODS: Tension (in newtons) of the ulnar, median,
      and radial nerves was measured simultaneously using 3 buckle force transducers in
      5 upper limb positions in 10 embalmed human cadavers (N=20 limbs). Repeated
      measures analysis of variance (ANOVA) with Bonferroni post hoc tests determined
      differences in tension among nerves and among limb positions. RESULTS: The
      addition of shoulder horizontal abduction (H.Abd; 12.62 N; 95% confidence
      interval [95% CI]=10.76, 14.47) and combined shoulder abduction and internal
      rotation (H.Abd+IR; 11.86 N; 95% CI=9.96, 13.77) to ULNT3 (scapular depression,
      shoulder abduction and external rotation, elbow flexion, forearm pronation, and
      wrist and finger extension) produced significantly greater ulnar nerve tension
      compared with the ULNT3 alone (8.71 N; 95% CI=7.25, 10.17). The ULNT3+H.Abd test
      demonstrated the greatest difference in tension among nerves (mean difference
      between ulnar and median nerves=11.87 N; 95% CI=9.80, 13.92; mean difference
      between ulnar and radial nerves=8.47 N; 95% CI=6.41, 10.53). LIMITATIONS: These
      results pertain only to the biomechanical plausibility of the ulnar nerve
      neurodynamic test and do not account for other factors that may affect the
      clinical application of this test. CONCLUSIONS: The ULNT3+H.Abd is a
      biomechanically plausible test for detecting peripheral neuropathic pain related
      to the ulnar nerve. In situations where the shoulder complex will not tolerate
      the combination of shoulder external rotation in abduction, performing upper limb
      neurodynamic tests with internal rotation instead of external rotation is a
      biomechanically plausible alternative.

PMID- 25592185
TI  - Constraint-Induced Movement Therapy After Injection of Botulinum Toxin Type A for
      a Patient With Chronic Stroke: One-Year Follow-up Case Report.
AB  - BACKGROUND AND PURPOSE: Spasticity, an aspect of upper motor neuron syndrome, is
      a widespread problem in patients with stroke. To date, no study has reported the
      long-term (up to 1 year) outcomes of botulinum toxin (BTX) injection in
      combination with constraint-induced movement therapy in patients with chronic
      stroke. In this case report, the long-term (1 year) effects of the combination of
      BTX type A injection and constraint-induced movement therapy on spasticity and
      arm function in a patient with chronic stroke and arm paresis are described. CASE
      DESCRIPTION: The patient was a 66-year-old man who had had an infarction in the
      right posterior limb of the internal capsule 4 years before the intervention. At
      screening, the patient was not able to voluntarily extend his interphalangeal or
      metacarpophalangeal joints beyond the 10 degrees required for constraint-induced
      movement therapy. From 12 days after BTX type A injection, the patient received 5
      hours of constraint-induced movement therapy for 10 weekdays. OUTCOMES: All
      outcome measures (Modified Ashworth Scale, Fugl-Meyer Assessment, Action Research
      Arm Test, and amount of use scale of the Motor Activity Log) improved
      substantially over the 1-year period (before intervention to 1 year after
      intervention). Repeat BTX type A injections were not necessary because muscle
      tone and arm function did not worsen during the observation period. DISCUSSION:
      The improved arm function may have reflected improvements in volitional movements
      and coordination or speed of movements in the paretic arm as a result of a
      reduction in spasticity, a reduction of learned nonuse behaviors, or use
      dependent plasticity after the combination of BTX type A injection and constraint
      induced movement therapy. In addition, the possibility of an influence of the
      passage of time or the Hawthorne effect cannot be ruled out. If this approach
      proves useful in future controlled studies, it may reduce the rising medical
      costs of the treatment of stroke.

PMID- 25592188
TI  - Cardiovascular Stress Induced by Whole-Body Vibration Exercise in Individuals
      With Chronic Stroke.
AB  - BACKGROUND: Although whole-body vibration (WBV) has sparked tremendous research
      interest in neurorehabilitation, the cardiovascular responses to WBV in people
      with stroke remain unknown. OBJECTIVE: The aim of this study was to determine the
      acute effects of different WBV protocols on oxygen consumption (Vo2), heart rate
      (HR), rate of perceived exertion (RPE), blood pressure (BP), and rate-pressure
      product (RPP) during the performance of 6 different exercises among people with
      chronic stroke (time since onset >=6 months). DESIGN: A repeated-measures design
      was used. METHODS: Each of the 48 participants experienced all 3 WBV protocols in
      separate sessions: (1) no WBV, (2) low-intensity WBV (peak acceleration=0.96 unit
      of gravity of Earth [g]), and (3) high-intensity WBV (1.61g). The order in which
      they encountered the WBV protocols was randomized, as was the order of exercises
      performed during each session. Oxygen consumption, HR, and RPE were measured
      throughout the study. Blood pressure and RPP were measured before and after each
      session. RESULTS: Low-intensity and high-intensity WBV induced significantly
      higher Vo2 by an average of 0.69 and 0.79 mL/kg/min, respectively, compared with
      the control condition. These protocols also increased HR by an average of 4 bpm.
      The 2 WBV protocols induced higher RPE than the control condition during static
      standing exercise only. Although the diastolic and systolic BP and RPP were
      increased at the end of each exercise session, the addition of WBV had no
      significant effect on these variables. LIMITATIONS: The results are generalizable
      only to ambulatory and community-dwelling people with chronic stroke.
      CONCLUSIONS: Addition of high- and low-intensity WBV significantly increased the
      Vo2 and HR, but the increase was modest. Thus, WBV should not pose any
      substantial cardiovascular hazard in people with chronic stroke.

PMID- 25592187
TI  - Factors Contributing to 50-ft Walking Speed and Observed Ethnic Differences in
      Older Community-Dwelling Mexican Americans and European Americans.
AB  - BACKGROUND: Mexican Americans comprise the most rapidly growing segment of the
      older US population and are reported to have poorer functional health than
      European Americans, but few studies have examined factors contributing to ethnic
      differences in walking speed between Mexican Americans and European Americans.
      OBJECTIVE: The purpose of this study was to examine factors that contribute to
      walking speed and observed ethnic differences in walking speed in older Mexican
      Americans and European Americans using the disablement process model (DPM) as a
      guide. DESIGN: This was an observational, cross-sectional study. METHODS:
      Participants were 703 Mexican American and European American older adults (aged
      65 years and older) who completed the baseline examination of the San Antonio
      Longitudinal Study of Aging (SALSA). Hierarchical regression models were
      performed to identify the contribution of contextual, lifestyle/anthropometric,
      disease, and impairment variables to walking speed and to ethnic differences in
      walking speed. RESULTS: The ethic difference in unadjusted mean walking speed
      (Mexican Americans=1.17 m/s, European Americans=1.29 m/s) was fully explained by
      adjustment for contextual (ie, age, sex, education, income) and
      lifestyle/anthropometric (ie, body mass index, height, physical activity)
      variables; adjusted mean walking speed in both ethnic groups was 1.23 m/s.
      Contextual variables explained 20.3% of the variance in walking speed, and
      lifestyle/anthropometric variables explained an additional 8.4%. Diseases (ie,
      diabetes, stroke, chronic obstructive pulmonary disease) explained an additional
      1.9% of the variance in walking speed; impairments (ie, FEV1, upper leg pain, and
      lower extremity strength and range of motion) contributed an additional 5.5%.
      Thus, both nonmodifiable (ie, contextual, height) and modifiable (ie,
      impairments, body mass index, physical activity) factors contributed to walking
      speed in older Mexican Americans and European Americans. LIMITATIONS: The study
      was conducted in a single geographic area and included only Mexican American
      Hispanic individuals. CONCLUSIONS: Walking speed in older Mexican Americans and
      European Americans is influenced by modifiable and nonmodifiable factors,
      underscoring the importance of the DPM framework, which incorporates both factors
      into the physical therapist patient/client management process.

PMID- 25592189
TI  - Longitudinal Evaluation of Muscle Composition Using Magnetic Resonance in 4 Boys
      With Duchenne Muscular Dystrophy: Case Series.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD), an inherited recessive X
      chromosome-linked disease, is the most severe childhood form of muscular
      dystrophy. Boys with DMD experience muscle loss, with infiltration of
      intramuscular fat into muscles. OBJECTIVES: This case series describes the
      progression of DMD in boys using magnetic resonance imaging (MRI) and magnetic
      resonance spectroscopy (MRS). Magnetic resonance results are then compared with
      an established functional timed test. METHODS: Four boys with DMD and 4 healthy
      age-matched controls were chosen from a larger cohort. Boys with DMD were
      assessed at 4 time points over 2 years, with controls assessed at baseline only.
      Progression of the disease was documented by assessing the plantar flexors using
      MRI and MRS techniques and by assessing ambulation using the 30-Foot Fast Walk
      Test. RESULTS: Transverse relaxation time (T2) values were elevated in all boys
      with DMD at baseline. The lipid ratio increased rapidly as the disease progressed
      in 2 boys. Discrete changes in T2 in the other 2 boys with DMD indicated a slower
      disease progression. Magnetic resonance imaging and MRS allowed monitoring of the
      disease over all time periods regardless of ambulation status. LIMITATIONS: The
      magnetic resonance data were collected with 2 different magnets at 2 different
      field strengths (1.5 and 3.0 T). Although we corrected for this difference, care
      must be taken in interpreting data when different image collection systems are
      used. This was a case series of 4 boys with DMD taken from a larger cohort study.
      CONCLUSIONS: Magnetic resonance imaging and MRS are objective, noninvasive
      techniques for measuring muscle pathology and can be used to detect discrete
      changes in both people who are ambulatory and those who are nonambulatory. These
      techniques should be considered when monitoring DMD progression and assessing
      efficacy of therapeutic interventions.

PMID- 25592190
TI  - Development of an adverse-event coping scale (AECS) using item response theory.
AB  - BACKGROUND: Adverse drug events (ADEs) cause significant morbidity and mortality
      to patients. A brief questionnaire asking patients how they coped with such
      problems could be a useful tool for providing timely interventions. OBJECTIVE:
      The aim of this study was to develop an adverse-event coping scale (AECS) to
      measure patients' coping responses to their ADE. METHODS: Data were collected
      from subjects recruited from community pharmacies. Psychometric analyses based on
      item response theory (IRT) were performed to calibrate items and assess
      reliability. Convergent validity was evaluated by testing a priori formulated
      hypotheses about expected correlations between the coping scores and other
      related scales. RESULTS: A total of 140 patients participated in this study by
      answering the developed items. Confirmatory factor analysis supported a one
      dimensional item bank with 11 items. The developed scale was reliable with the
      reliability coefficient of 0.82. Coping scores were positively correlated with
      seriousness of the ADE and health literacy, but not coping self-efficacy.
      Overall, results suggest that the score reflects problem magnitude and coping
      effort rather than coping efficacy. CONCLUSION: A high score on the AECS
      indicates an ADE serious enough to prompt a patient to invest substantial efforts
      to cope with it. The final AECS item bank and its short-form can help clinicians
      better understand their patients' ADE-coping efforts.

PMID- 25592191
TI  - Community, autonomy and bespoke services: Independent community pharmacy practice
      in hyperdiverse, London communities.
AB  - BACKGROUND: The landscape of pharmacy continues to evolve including in Great
      Britain, where, by 2012, almost 50% of pharmacy contracts were held by just 9
      national chains. OBJECTIVE: To further explicate the concept of 'independence' as
      it was positioned by independent pharmacists, particularly examining personal
      interpretations of their role in contemporary pharmacy and health care delivery.
      METHODS: Research was situated in East and South-east London between 2008 and
      2009. The study took an ethnographic approach; combining participant observation
      within 7 pharmacies and 36 active interviews with pharmacists. Recruitment
      criteria demanded that pharmacists self-identified as independent and were either
      owners or managers in sole-owned or independent chain pharmacies. RESULTS:
      Independence was expressed through a framework of three overarching themes:
      autonomy, engagement and bespoke practice. Autonomy formed the basis of
      professional expression ultimately enabling pharmacists to exercise control over
      customer relationships. This facilitated engagement with communities and
      individuals and ultimately made possible an offering of a bespoke 'personal'
      service. The diverse urban environment was a space where independence was seen to
      be of particular value. The complexity of this setting was used symbolically to
      support the need for independent thinking. These themes are examined through
      stories of 'acceptance' and developing pharmacy 'communities' alongside the
      practise of maintaining personal relationships to provide a distinct service
      offer. CONCLUSIONS: This study highlights distinct 'independent' expression of
      professional identity and suggests the need to assess the value of independent
      community pharmacy as being different from but complementary to the service
      provided by multiples/large chains.

PMID- 25592192
TI  - Plain magnetic resonance imaging as an alternative in evaluating inflammation and
      bowel damage in inflammatory bowel disease--a prospective comparison with
      conventional magnetic resonance follow-through.
AB  - OBJECTIVE: To compare prospectively the diagnostic accuracy of magnetic resonance
      imaging (MRI) without use of contrast medium orally or intravenously (plain MRI)
      with magnetic resonance follow-through (MRFT) in patients with inflammatory bowel
      disease (IBD). MATERIAL AND METHODS: Plain MRI was carried out in addition to
      MRFT, to which the patients were referred. All patients underwent both
      examinations on the same day. For the evaluation, the bowel was divided into nine
      segments. Two radiologists, blinded to clinical findings, evaluated bowel wall
      thickness, diffusion weighted imaging (DWI), and other inflammatory changes in
      each bowel segments. Further, hyperenhancement of the bowel was also evaluated in
      MRFT. RESULTS: A total of 100 patients (40 males and 60 females; median age:
      38.5; range: 19-90) were enrolled; 44 with Crohn's disease (CD), 25 with
      ulcerative colitis (UC), 24 with IBD unclassified (IBD-U), and 7 had other
      diagnosis. Sensitivity, specificity, and accuracy in CD ranged 50-86%, 93-94%,
      and 91-92% for wall thickening and 49-82%, 85-93%, and 84-89% for DWI,
      respectively. Sensitivity, specificity, and accuracy in UC range 0-40%, 87-100%,
      and 80-100% for wall thickening and 0-52%, 83-94% and 76-92% for DWI,
      respectively. The kappa values for bowel wall thickening, DWI, and mural
      hyperenhancement were detected with fair agreement (kappa = 0.26-0.39) at both
      MRI examinations, whereas only bowel wall thickening in MRFT were detected with
      moderate agreement (kappa = 0.47) Conclusion. Plain MRI cannot currently replace
      MRFT in the workup of patients with IBD. Further research on plain MRI is needed
      to improve the protocol.

PMID- 25592193
TI  - Dietary diabetes risk reduction score, race and ethnicity, and risk of type 2
      diabetes in women.
AB  - OBJECTIVE: To evaluate racial and ethnic differences in the association between a
      dietary diabetes risk reduction score and incidence of type 2 diabetes in U.S.
      white and minority women. RESEARCH DESIGN AND METHODS: We followed 156,030 non
      Hispanic white (NHW), 2,026 Asian, 2,053 Hispanic, and 2,307 black women in the
      Nurses' Health Study (NHS) (1980-2008) and NHS II (1991-2009). A time-updated
      dietary diabetes risk reduction score (range 8-32) was created by adding points
      corresponding with each quartile of intake of eight dietary factors (1 = highest
      risk; 4 = lowest risk). A higher score indicates a healthier overall diet.
      RESULTS: We documented 10,922 incident type 2 diabetes cases in NHW, 157 in
      Asian, 193 in Hispanic, and 307 in black women. Multivariable-adjusted pooled
      hazard ratio across two cohorts for a 10th-90th percentile range difference in
      dietary diabetes risk reduction score was 0.49 (95% CI 0.46, 0.52) for NHW, 0.53
      (0.31, 0.92) for Asian, 0.45 (0.29, 0.70) for Hispanic, 0.68 (0.47, 0.98) for
      black, and 0.58 (0.46, 0.74) for overall minority women (P for interaction
      between minority race/ethnicity and dietary score = 0.08). The absolute risk
      difference (cases per 1,000 person-years) for the same contrast in dietary score
      was -5.3 (-7.8, -2.7) for NHW, -7.2 (-22.9, 8.4) for Asian, -11.6 (-26.7, 3.5)
      for Hispanic, -6.8 (-19.5, 5.9) for black, and -8.0 (-15.6, -0.5) for overall
      minority women (P for interaction = 0.04). CONCLUSIONS: A higher dietary diabetes
      risk reduction score was inversely associated with risk of type 2 diabetes in all
      racial and ethnic groups, but the absolute risk difference was greater in
      minority women.

PMID- 25592194
TI  - Change in medical spending attributable to diabetes: national data from 1987 to
      2011.
AB  - OBJECTIVE: Diabetes care has changed substantially in the past 2 decades. We
      examined the change in medical spending and use related to diabetes between 1987
      and 2011. RESEARCH DESIGN AND METHODS: Using the 1987 National Medical
      Expenditure Survey and the Medical Expenditure Panel Surveys in 2000-2001 and
      2010-2011, we compared per person medical expenditures and uses among adults >=
      18 years of age with or without diabetes at the three time points. Types of
      medical services included inpatient care, emergency room (ER) visits, outpatient
      visits, prescription drugs, and others. We also examined the changes in unit
      cost, defined by the expenditure per encounter for medical services. RESULTS: The
      excess medical spending attributed to diabetes was $2,588 (95% CI, $2,265 to
      $3,104), $4,205 ($3,746 to $4,920), and $5,378 ($5,129 to $5,688) per person,
      respectively, in 1987, 2000-2001, and 2010-2011. Of the $2,790 increase,
      prescription medication accounted for 55%; inpatient visits accounted for 24%;
      outpatient visits accounted for 15%; and ER visits and other medical spending
      accounted for 6%. The growth in prescription medication spending was due to the
      increase in both the volume of use and unit cost, whereas the increase in
      outpatient expenditure was almost entirely driven by more visits. In contrast,
      the increase in inpatient and ER expenditures was caused by the rise of unit
      costs. CONCLUSIONS: In the past 2 decades, managing diabetes has become more
      expensive, mostly due to the higher spending on drugs. Further studies are needed
      to assess the cost-effectiveness of increased spending on drugs.

PMID- 25592195
TI  - Tight glycemic control and use of hypoglycemic medications in older veterans with
      type 2 diabetes and comorbid dementia.
AB  - OBJECTIVE: Older adults with diabetes and dementia are at increased risk for
      hypoglycemia and other adverse events associated with tight glycemic control and
      are unlikely to experience long-term benefits. We examined risk factors for tight
      glycemic control in this population and use of medications associated with a high
      risk of hypoglycemia in the subset with tight control. RESEARCH DESIGN AND
      METHODS: This retrospective cohort study of national Veterans Affairs (VA)
      administrative/clinical data and Medicare claims for fiscal years (FYs) 2008-2009
      included 15,880 veterans aged >= 65 years with type 2 diabetes and dementia and
      prescribed antidiabetic medication. Multivariable regression analyses were used
      to identify sociodemographic and clinical predictors of hemoglobin A1c (HbA1c)
      control (tight, moderate, poor, or not monitored) and, in patients with tight
      control, subsequent use of medication associated with a high risk of hypoglycemia
      (sulfonylureas, insulin). RESULTS: Fifty-two percent of patients had tight
      glycemic control (HbA1c <7% [53 mmol/mol]). Specific comorbidities, older age,
      and recent weight loss were associated with greater odds of tight versus moderate
      control, whereas Hispanic ethnicity and obesity were associated with lower odds
      of tight control. Among tightly controlled patients, 75% used sulfonylureas
      and/or insulin, with higher odds in patients who were male, black, or aged >= 75
      years; had a hospital or nursing home stay in FY2008; or had congestive heart
      failure, renal failure, or peripheral vascular disease. CONCLUSIONS: Many older
      veterans with diabetes and dementia are at high risk for hypoglycemia associated
      with intense diabetes treatment and may be candidates for deintensification or
      alteration of diabetes medications.

PMID- 25592196
TI  - Lipoprotein particles and incident type 2 diabetes in the multi-ethnic study of
      atherosclerosis.
AB  - OBJECTIVE: In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated
      associations of baseline levels of a lipoprotein-based insulin resistance (IR)
      index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids,
      with incident type 2 diabetes, independent of confounders, glucose, insulin, and
      HOMA-IR. RESEARCH DESIGN AND METHODS: Among 5,314 adults aged 45-84 years without
      baseline diabetes or cardiovascular disease, 656 cases of diabetes were
      identified during a mean follow-up of 7.7 years. Lipoprotein particle
      concentrations, size, and LP-IR were determined by nuclear magnetic resonance
      spectroscopy of stored baseline plasma. Potential effect modification, by
      race/ethnicity, sex, baseline use of lipid-lowering medications or hormone
      therapy, or glucose strata (<90, 90-99, and >= 100 mg/dL), was also evaluated.
      RESULTS: Higher levels of LP-IR, large VLDL particles (VLDL-P), small LDL
      particles, triglycerides (TG), and TG-to-HDL cholesterol (HDL-C) ratio and lower
      levels of large HDL particles, smaller HDL and LDL size, and larger VLDL size
      were significantly associated with incident diabetes adjusted for confounders and
      glucose or insulin. These also were similar by race/ethnicity, sex, and treatment
      group. Associations were similar for LP-IR, large VLDL-P, mean VLDL size, TG, and
      TG-to-HDL-C ratio; they persisted for LP-IR, large VLDL-P, or mean VLDL size
      adjusted for HOMA-IR or TG-to-HDL-C ratio and glucose but not for the TG-to-HDL-C
      ratio adjusted for LP-IR or for HOMA-IR or insulin if adjusted for LP-IR and
      glucose. CONCLUSIONS: Among ethnically diverse men and women, LP-IR, large VLDL
      P, large VLDL size, TG, and TG-to-HDL-C ratio were associated with incident
      diabetes independent of established risk factors, glucose, insulin, or HOMA-IR,
      as well as the use of lipid-lowering medications or hormone therapy.

PMID- 25592197
TI  - Dapagliflozin improves glycemic control and reduces body weight as add-on therapy
      to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical
      trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of dapagliflozin in patients with
      type 2 diabetes inadequately controlled with metformin and sulfonylurea. RESEARCH
      DESIGN AND METHODS: Patients with HbA1c of 7.0% (53 mmol/mol) to 10.5% (91
      mmol/mol) receiving sulfonylurea and metformin were randomized to receive
      dapagliflozin 10 mg/day (n = 109) or placebo (n = 109) for 24 weeks. RESULTS:
      HbA1c (baseline: dapagliflozin 8.08% [65 mmol/mol]; placebo 8.24% [67 mmol/mol])
      and fasting plasma glucose (baseline: dapagliflozin 167.4 mg/dL [9.29 mmol/L];
      placebo 180.5 mg/dL [10.02 mmol/L]) significantly improved from baseline with
      dapagliflozin (placebo-subtracted change -0.69% [-7.5 mmol/mol], P < 0.0001; 
      33.5 mg/dL [-1.86 mmol/L], P < 0.0001, respectively). More patients achieved a
      therapeutic glycemic response (HbA1c <7.0% [53 mmol/mol]) with dapagliflozin
      (31.8%) versus placebo (11.1%) (P < 0.0001). Body weight and systolic blood
      pressure were significantly reduced from baseline over 24 and 8 weeks,
      respectively, with dapagliflozin (placebo-subtracted change -2.1 kg, P < 0.0001; 
      3.8 mmHg, P = 0.0250). Patients receiving dapagliflozin showed placebo-subtracted
      increases in total, LDL, and HDL cholesterol (11.4 mg/dL, P = 0.0091; 11.4 mg/dL,
      P = 0.0030; 2.2 mg/dL, P = 0.0172, respectively) with no change in LDL/HDL
      cholesterol ratio (0.1; P = 0.2008) or triglycerides (-16.5 mg/dL; P = 0.1755).
      Adverse events occurred in 48.6% of patients receiving dapagliflozin and 51.4%
      receiving placebo. Significantly more patients with dapagliflozin compared with
      placebo experienced hypoglycemia (12.8 vs. 3.7%; P = 0.024) and genital
      infections (5.5 vs. 0%; P = 0.029). Events of urinary tract infection were
      reported by 6.4% of patients in both groups. CONCLUSIONS: Dapagliflozin was well
      tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea.
      Adverse effects included hypoglycemia and genital infections.

PMID- 25592198
TI  - Effects of physical activity and exercise training on cardiovascular risk in
      coronary artery disease patients with and without type 2 diabetes.
AB  - OBJECTIVE: Leisure-time physical activity (LTPA) and exercise training are
      essential parts of current guidelines for patients with coronary artery disease
      (CAD). However, the contributions of LTPA and exercise training to cardiovascular
      (CV) risk in CAD patients with type 2 diabetes (T2D) are not well established.
      RESEARCH DESIGN AND METHODS: We examined the effects of LTPA (n = 539 and n =
      507; with and without T2D, respectively) and 2-year controlled, home-based
      exercise training (n = 63 plus 64 control subjects with T2D and n = 72 plus 68
      control subjects without T2D) on the CV risk profile and composite end point
      among CAD patients. RESULTS: During the 2-year follow-up, patients with reduced
      LTPA at baseline had an increased risk of CV events (adjusted hazard ratio 2.3
      [95% CI 1.1-5.1; P = 0.033], 2.1 [1.1-4.2; P = 0.027], and 2.0 [1.0-3.9; P =
      0.044] for no LTPA, LTPA irregularly, and LTPA two to three times weekly,
      respectively) compared with those with LTPA more than three times weekly. Among
      patients who completed the 2-year exercise intervention, exercise training
      resulted in favorable changes in exercise capacity both in CAD patients with T2D
      (+0.2 +/- 0.8 vs. -0.1 +/- 0.8 MET, P = 0.030) and without T2D (+0.3 +/- 0.7 vs. 
      0.1 +/- 0.5 MET, P = 0.002) as compared with the control group but did not have
      any significant effects on major metabolic or autonomic nervous system risk
      factors in CAD patients with or without T2D. CONCLUSIONS: There is an inverse
      association between habitual LTPA and short-term CV outcome, but controlled, home
      based exercise training has only minor effects on the CV risk profile in CAD
      patients with T2D.

PMID- 25592199
TI  - Cross-comparison of MRCGP & MRCP(UK) in a database linkage study of 2,284
      candidates taking both examinations: assessment of validity and differential
      performance by ethnicity.
AB  - BACKGROUND: MRCGP and MRCP(UK) are the main entry qualifications for UK doctors
      entering general [family] practice or hospital [internal] medicine. The
      performance of MRCP(UK) candidates who subsequently take MRCGP allows validation
      of each assessment. In the UK, underperformance of ethnic minority doctors taking
      MRCGP has had a high political profile, with a Judicial Review in the High Court
      in April 2014 for alleged racial discrimination. Although the legal challenge was
      dismissed, substantial performance differences between white and BME (Black and
      Minority Ethnic) doctors undoubtedly exist. Understanding ethnic differences can
      be helped by comparing the performance of doctors who take both MRCGP and
      MRCP(UK). METHODS: We identified 2,284 candidates who had taken one or more parts
      of both assessments, MRCP(UK) typically being taken 3.7 years before MRCGP. We
      analyzed performance on knowledge-based MCQs (MRCP(UK) Parts 1 and 2 and MRCGP
      Applied Knowledge Test (AKT)) and clinical examinations (MRCGP Clinical Skills
      Assessment (CSA) and MRCP(UK) Practical Assessment of Clinical Skills (PACES)).
      RESULTS: Correlations between MRCGP and MRCP(UK) were high, disattenuated
      correlations for MRCGP AKT with MRCP(UK) Parts 1 and 2 being 0.748 and 0.698, and
      for CSA and PACES being 0.636. BME candidates performed less well on all five
      assessments (P < .001). Correlations disaggregated by ethnicity were complex,
      MRCGP AKT showing similar correlations with Part1/Part2/PACES in White and BME
      candidates, but CSA showing stronger correlations with Part1/Part2/PACES in BME
      candidates than in White candidates. CSA changed its scoring method during the
      study; multiple regression showed the newer CSA was better predicted by PACES
      than the previous CSA. CONCLUSIONS: High correlations between MRCGP and MRCP(UK)
      support the validity of each, suggesting they assess knowledge cognate to both
      assessments. Detailed analyses by candidate ethnicity show that although White
      candidates out-perform BME candidates, the differences are largely mirrored
      across the two examinations. Whilst the reason for the differential performance
      is unclear, the similarity of the effects in independent knowledge and clinical
      examinations suggests the differences are unlikely to result from specific
      features of either assessment and most likely represent true differences in
      ability.

PMID- 25592200
TI  - Stimulation of peroxisome proliferator-activated receptor gamma inhibits estrogen
      receptor alpha transcriptional activity in endometrial carcinoma cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) and estrogen
      receptor (ER) belong to a family of nuclear hormone receptors that have been
      demonstrated to affect each other's transcriptional activity. At present, little
      is known regarding the effect of PPARgamma on ER-mediated transcriptional
      activity in endometrial carcinoma. In the present study, we aimed to demonstrate
      the correlation between PPARgamma and ER in endometrial carcinoma and to
      elucidate the biological effects of abnormal expression of PPARgamma on
      endometrial carcinoma cell lines. Immunohistochemical and western blotting
      methods were used to detect the expression of PPARgamma, ERalpha and ERbeta in
      normal and malignant endometrium. Next, we performed transient transfection to
      assess the interaction between PPARgamma and ER in vitro. Furthermore, we
      examined cell migration, invasion and proliferation as a biological counterpart.
      PPARgamma and ERalpha expression levels were significantly associated with
      pathological grade and clinical stage in endometrial carcinoma (P<0.05). Pearson
      correlation analysis revealed that PPARgamma expression was positively correlated
      with ERalpha expression (P<0.05). Using KLE and ERalpha-positive cells (ECC-1),
      we demonstrated that the PPARgamma regulation of ER expression occurred
      predominantly through ERalpha. Moreover, our findings suggest that PPARgamma
      activation inhibited the migration, invasion and proliferation of endometrial
      carcinoma cells; ECC-1 cells were more sensitive to this inhibition. The present
      study demonstrated that PPARgamma activation inhibited ERalpha expression in
      ERalpha-positive endometrial carcinoma cell lines. This crosstalk may facilitate
      the development of novel therapeutic methods targeting PPARgamma in endometrial
      carcinoma treatment, particularly ERalpha-positive carcinomas.

PMID- 25592202
TI  - Maternal immune activation induces changes in myelin and metabolic proteins, some
      of which can be prevented with risperidone in adolescence.
AB  - BACKGROUND: Maternal infection is a risk factor for schizophrenia but the
      molecular and cellular mechanisms are not fully known. Myelin abnormalities are
      amongst the most robust neuropathological changes observed in schizophrenia, and
      preliminary evidence suggests that prenatal inflammation may play a role.
      METHODS: Label-free liquid chromatography-mass spectrometry was performed on the
      prefrontal cortex (PFC) of adult rat offspring born to dams that were exposed on
      gestational day 15 to the viral mimic polyinosinic:polycytidylic acid [poly(I:C),
      4 mg/kg] or saline and treated with the atypical antipsychotic drug risperidone
      (0.045 mg/kg) or saline in adolescence. Western blotting was employed to validate
      protein changes. RESULTS: Over 1,000 proteins were quantified in the PFC with
      pathway analyses implicating changes in core metabolic pathways, following
      prenatal poly(I:C) exposure. Some of these protein changes were absent in the PFC
      of poly(I:C)-treated offspring that subsequently received risperidone treatment
      in adolescence. Particularly interesting reductions in the expression of the
      myelin-related proteins myelin basic protein isoform 3 (MBP1) and rhombex 29 were
      observed, which were reversed by risperidone treatment. Validation by Western
      blotting confirmed changes in MBP1 and mitogen-activated kinase 1 (MAPK1).
      Western blotting was extended to assess the MAPK signalling proteins due to their
      roles in inflammation, namely phosphorylated MAPK1 and phosphorylated MAPK
      activated protein kinase 2. Both were upregulated by poly(I:C) treatment and
      reversed by risperidone treatment. CONCLUSIONS: Overall, our data suggest that
      maternal inflammation may contribute to an increased risk for schizophrenia
      through mechanisms involving metabolic function and myelin formation and that
      risperidone in adolescence may prevent or reverse such changes.

PMID- 25592201
TI  - Waste the waist: a pilot randomised controlled trial of a primary care based
      intervention to support lifestyle change in people with high cardiovascular risk.
AB  - BACKGROUND: In the UK, thousands of people with high cardiovascular risk are
      being identified by a national risk-assessment programme (NHS Health Checks).
      Waste the Waist is an evidence-informed, theory-driven (modified Health Action
      Process Approach), group-based intervention designed to promote healthy eating
      and physical activity for people with high cardiovascular risk. This pilot
      randomised controlled trial aimed to assess the feasibility of delivering the
      Waste the Waist intervention in UK primary care and of conducting a full-scale
      randomised controlled trial. We also conducted exploratory analyses of changes in
      weight. METHODS: Patients aged 40-74 with a Body Mass Index of 28 or more and
      high cardiovascular risk were identified from risk-assessment data or from
      practice database searches. Participants were randomised, using an online
      computerised randomisation algorithm, to receive usual care and standardised
      information on cardiovascular risk and lifestyle (Controls) or nine sessions of
      the Waste the Waist programme (Intervention). Group allocation was concealed
      until the point of randomisation. Thereafter, the statistician, but not
      participants or data collectors were blinded to group allocation. Weight,
      physical activity (accelerometry) and cardiovascular risk markers (blood tests)
      were measured at 0, 4 and 12 months. RESULTS: 108 participants (22% of those
      approached) were recruited (55 intervention, 53 controls) from 6 practices and
      89% provided data at both 4 and 12 months. Participants had a mean age of 65 and
      70% were male. Intervention participants attended 72% of group sessions. Based on
      last observations carried forward, the intervention group did not lose
      significantly more weight than controls at 12 months, although the difference was
      significant when co-interventions and co-morbidities that could affect weight
      were taken into account (Mean Diff 2.6Kg. 95%CI: -4.8 to -0.3, p = 0.025). No
      significant differences were found in physical activity. CONCLUSIONS: The Waste
      the Waist intervention is deliverable in UK primary care, has acceptable
      recruitment and retention rates and produces promising preliminary weight loss
      results. Subject to refinement of the physical activity component, it is now
      ready for evaluation in a full-scale trial. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN10707899 .

PMID- 25592203
TI  - Insomnia is associated with quality of life impairment in medical-surgical
      intensive care unit survivors.
AB  - OBJECTIVES: To examine the prevalence of insomnia and its relationship to health
      related quality of life (HRQOL) post-intensive care unit (ICU). BACKGROUND: The
      burden of post-ICU insomnia is unknown. METHODS: This cross-sectional study
      examined data from 120 patients with an ICU stay >24 h. Pre-hospital health was
      assessed in-hospital. Insomnia, HRQOL and post-ICU psychiatric symptoms were
      assessed at 12 months post-ICU. RESULTS: Over one-quarter (28%) of subjects met
      insomnia criteria at 12 months post-ICU. Post-ICU insomnia was independently
      associated with worse mental HRQOL (P < 0.01), as well as worse scores on the
      HRQOL sub-domains of bodily pain (P < 0.001), vitality (P < 0.05) and physical
      function (P < 0.05). However, these associations were no longer significant after
      adjusting for post-ICU psychiatric symptoms (P = 0.33). CONCLUSIONS: Insomnia is
      common among ICU survivors. Post-ICU insomnia is significantly associated with
      mental HRQOL and could identify ICU survivors who may benefit from further
      psychiatric evaluation.

PMID- 25592204
TI  - Managing the acute coronary syndrome patient: Evidence based recommendations for
      anti-platelet therapy.
AB  - Acute coronary syndrome (ACS) is best managed by a multidisciplinary team in
      which primary care physicians, physician assistants, nurse practitioners, and
      pharmacists play a key role. This article summarizes recent updates to American
      College of Cardiology Foundation/American Heart Association guidelines for the
      management of unstable angina (UA)/non ST-segment elevation ACS (NSTE-ACS) and ST
      segment elevation myocardial infarction (STEMI), focusing on antiplatelet
      therapy. Dual antiplatelet therapy comprising aspirin plus a P2Y12 inhibitor
      (clopidogrel, prasugrel, or ticagrelor) is recommended for patients with NSTE
      ACS, and those with STEMI both during and after reperfusion. The guidelines
      provide recommendations regarding the utilization of P2Y12 inhibitors in specific
      circumstances and are discussed in this review. Health care teams with a key role
      in post-ACS care need to be familiar with the latest guidelines and support
      patients with education on risk reduction and the benefits of long-term
      medication adherence. 

PMID- 25592205
TI  - Computerized auditory cognitive training to improve cognition and functional
      outcomes in patients with heart failure: Results of a pilot study.
AB  - OBJECTIVES: Feasibility and efficacy of computerized auditory cognitive training
      (ACT) was examined among patients with heart failure (HF). BACKGROUND:
      Individuals with HF have four times increased risk of cognitive impairment, yet
      cognitive intervention studies are sparse. METHODS: A pilot randomized controlled
      design was used. RESULTS: The ACT group (n = 9) and control group (n = 8) had
      similar baseline characteristics. Seven participants (78%) completed >= 18 hours
      of ACT. Medium effect sizes were observed for improved cognition as indicated by
      auditory processing speed (d = 0.78), speech processing (d = 0.88), and working
      memory (d = 0.44-0.50). Small effect sizes were found for improved functional
      outcomes including HF selfcare (d = 0.34), Timed Instrumental Activities of Daily
      Living (d = 0.32), Six-Minute Walk Test (d = 0.38) and Short-Form-36 (d = 0.22)
      relative to controls. CONCLUSION: Results indicated ACT is feasible among persons
      with HF. Despite a small sample size, ACT showed potential for improved speed of
      processing and working memory and improved functional outcomes, and warrants
      further exploration.

PMID- 25592206
TI  - Efficacy of noninvasive ventilation after planned extubation: A systematic review
      and meta-analysis of randomized controlled trials.
AB  - The objective our meta-analysis is to update the evidence on the efficacy of
      noninvasive ventilation (NIV) compared with conventional oxygen therapy after
      planned extubation. We did a systematic literature review of database, including
      Pubmed, EMBASE, and Cochrane. We included randomized controlled trials comparing
      NIV with conventional oxygen therapy after planned extubation in medical
      intensive care unit (ICU) in our analysis. The results of our meta-analysis is
      consistent with the results of previous reviews and show that NIV decreased
      reintubation rate significantly as compared to conventional oxygen therapy in
      chronic obstructive pulmonary disease (COPD) and patients at high risk for
      extubation failure; COPD (RR, 0.33; 95% CI, 0.16-0.69; I2 = 0), high risk (RR,
      0.47; 95% CI, 0.32-0.70; I2 = 0). However, in a mixed medical ICU population,
      there was no statistical difference of reintubation rate between the two groups
      (RR, 0.66; 95% CI, 0.25-1.73; I2 = 68%). Our study suggests that use of NIV after
      planned extubation significantly decreases the reintubation rate in COPD patients
      and patients at high risk for extubation failure, confirming the findings of
      previous reviews. There is no difference in the reintubation rate between the two
      groups in the mixed medical ICU population. 

PMID- 25592207
TI  - Chemotherapy for soft-tissue sarcomas.
AB  - Cytotoxic chemotherapy with doxorubicin in combination with ifosfamide or
      dacarbazine, or gemcitabine in combination with docetaxel, continues to be the
      mainstay of treatment of metastatic soft-tissue sarcomas. A goal-oriented
      approach that includes careful consideration of histology, performance status,
      sites of disease, patient goals, and intent of treatment is vital to the
      formulation of an effective treatment plan. Both single-agent and combination
      chemotherapy regimens are available and should be chosen carefully to fit the
      clinical situation and patient goals. In patients with localized soft-tissue
      sarcoma who have a high likelihood of recurrent disease, systemic therapy should
      be strongly considered. The ability to demonstrate efficacy in the neoadjuvant
      setting may help avoid unnecessary treatment-related toxicity in patients with
      poor response and maximize recurrence-free survival in patients who do
      demonstrate an excellent response to therapy. 

PMID- 25592208
TI  - Chemotherapy in soft-tissue sarcoma: where do we go from here?

PMID- 25592209
TI  - Cytotoxic chemotherapy for adult soft-tissue sarcomas: a lesson in humility.

PMID- 25592210
TI  - ADT risks and side effects in advanced prostate cancer: cardiovascular and acute
      renal injury.
AB  - Androgen deprivation therapy (ADT) is key to the treatment of men with advanced
      prostate cancer. ADT can consist of surgical (bilateral orchiectomy) or medical
      strategies (eg, luteinizing hormone-releasing hormone agonists or gonadotropin
      releasing hormone [GnRH] antagonists). The substantial reduction of testosterone
      levels achieved with ADT is associated with numerous well-characterized side
      effects, the management of which are key to patients' quality of life. More
      recently, a group of metabolic changes (dyslipidemia, hyperglycemia, others) that
      carry an increased risk of diabetes and cardiovascular disease have been reported
      in men receiving ADT. We review recent evidence suggesting an increased risk of
      pneumonia, cardiovascular disease, and acute kidney injury in men treated with
      ADT and consider whether the incidence of such events differs with the treatment
      modality. We discuss possible mechanisms by which such events might be mediated,
      including the roles of testosterone and the GnRH receptor, and consider current
      guidelines in light of these data. 

PMID- 25592211
TI  - The double-edged sword of ADT: emerging evidence of cardiovascular, pulmonary,
      and renal risks.

PMID- 25592212
TI  - Big data: not really the same as level 1 data.

PMID- 25592214
TI  - Interhemispheric insular and inferior frontal connectivity are associated with
      substance abuse in a psychiatric population.
AB  - Substance abuse is highly comorbid with major psychiatric disorders. While the
      neural underpinnings of drug abuse have been studied extensively, most existing
      studies compare drug users without comorbidities and healthy, non-user controls.
      Such studies do not generalize well to typical patients with substance abuse
      disorders. Therefore, we studied a population of psychiatric inpatients (n = 151)
      with a range of mental illnesses. Psychiatric disorders were diagnosed via
      structured interviews. Sixty-five percent of patients met criteria for at least
      one substance use disorder. Patients were recruited for resting state functional
      connectivity (RSFC) and diffusion tensor imaging (DTI) experiments to examine the
      interhemispheric connectivity between brain regions hypothesized to be involved
      in drug addiction, namely: the inferior, medial, and superior frontal gyri;
      insula; striatum; and anterior cingulate cortex. The World Health Organization
      Alcohol, Smoking, and Substance Involvement Screening Test (WHOA) questionnaire
      was used to further assess drug use. An association between use of tobacco,
      alcohol, cocaine, sedatives, and hallucinogens with increased insular
      interhemispheric connectivity was observed. In addition, increased inferior
      frontal gyrus interhemispheric connectivity was associated with amphetamine and
      inhalant use. Our results suggest that increased inter-hemispheric insula
      connectivity is associated with the use of several drugs of abuse. Importantly,
      psychiatric inpatients without a history of drug dependence were used as an
      ecologically valid control group rather than the more typical comparison between
      "mentally ill vs. healthy control" populations. We suggest that dysfunction of
      interhemispheric connectivity of the insula and to a lesser extent of the
      inferior frontal gyrus, are related to drug abuse in psychiatric populations.

PMID- 25592213
TI  - ASICs and cardiovascular homeostasis.
AB  - In this review we address primarily the role of ASICs in determining sensory
      signals from arterial baroreceptors, peripheral chemoreceptors, and
      cardiopulmonary and somatic afferents. Alterations in these sensory signals
      during acute cardiovascular stresses result in changes in sympathetic and
      parasympathetic activities that restore cardiovascular homeostasis. In
      pathological states, however, chronic dysfunctions of these afferents result in
      serious sympatho-vagal imbalances with significant increases in mortality and
      morbidity. We identified a role for ASIC2 in the mechano-sensitivity of aortic
      baroreceptors and of ASIC3 in the pH sensitivity of carotid bodies. In
      spontaneously hypertensive rats, we reported decreased expression of ASIC2 in
      nodose ganglia neurons and overexpression of ASIC3 in carotid bodies. This
      reciprocal expression of ASIC2 and ASIC3 results in reciprocal changes in sensory
      sensitivity of baro- and chemoreceptors and a consequential synergistic
      exaggeration sympathetic nerve activity. A similar reciprocal sensory
      dysautonomia prevails in heart failure and increases the risk of mortality. There
      is also evidence that ASIC heteromers in skeletal muscle afferents contribute
      significantly to the exercise pressor reflex. In cardiac muscle afferents of the
      dorsal root ganglia, they contribute to nociception and to the detrimental
      sympathetic activation during ischemia. Finally, we report that an inhibitory
      influence of ASIC2-mediated baroreceptor activity suppresses the sympatho
      excitatory reflexes of the chemoreceptors and skeletal muscle afferents, as well
      as the ASIC1a-mediated excitation of central neurons during fear, threat, or
      panic. The translational potential of activation of ASIC2 in cardiovascular
      disease states may be a beneficial sympatho-inhibition and parasympathetic
      activation. This article is part of the Special Issue entitled 'Acid-Sensing Ion
      Channels in the Nervous System'. 

PMID- 25592216
TI  - Commentary on: Muscle dysmorphia: could it be classified as an addiction to body
      image?
AB  - This commentary addresses a recent article on the characterization of muscle
      dysmorphia as an addiction. The commentary examines the larger issue of the
      possible relationship of compulsions to addictions. It also questions whether
      understanding the heterogeneity within disorders may be a useful tactic to
      develop more targeted treatment approaches. 

PMID- 25592215
TI  - ASICs and neuropeptides.
AB  - The acid sensing ion channels (ASICs) are proton-gated cation channels expressed
      throughout the nervous system. ASICs are activated during acidic pH fluctuations,
      and recent work suggests that they are involved in excitatory synaptic
      transmission. ASICs can also induce neuronal degeneration and death during
      pathological extracellular acidosis caused by ischemia, autoimmune inflammation,
      and traumatic injury. Many endogenous neuromodulators target ASICs to affect
      their biophysical characteristics and contributions to neuronal activity. One of
      the most unconventional types of modulation occurs with the interaction of ASICs
      and neuropeptides. Collectively, FMRFamide-related peptides and dynorphins
      potentiate ASIC activity by decreasing the proton-sensitivity of steady state
      desensitization independent of G protein-coupled receptor activation. By
      decreasing the proton-sensitivity of steady state desensitization, the FMRFamide
      related peptides and dynorphins permit ASICs to remain active at more acidic
      basal pH. Unlike the dynorphins, some FMRFamide-related peptides also potentiate
      ASIC activity by slowing inactivation and increasing the sustained current.
      Through mechanistic studies, the modulation of ASICs by FMRFamide-related
      peptides and dynorphins appears to be through distinct interactions with the
      extracellular domain of ASICs. Dynorphins are expressed throughout the nervous
      system and can increase neuronal death during prolonged extracellular acidosis,
      suggesting that the interaction between dynorphins and ASICs may have important
      consequences for the prevention of neurological injury. The overlap in expression
      of FMRFamide-related peptides with ASICs in the dorsal horn of the spinal cord
      suggests that their interaction may have important consequences for the treatment
      of pain during injury and inflammation. This article is part of the Special Issue
      entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25592217
TI  - Commentary on: Muscle dysmorphia: could it be classified as an addiction to body
      image?

PMID- 25592219
TI  - Simulations of room temperature ionic liquids: from polarizable to coarse-grained
      force fields.
AB  - Room temperature ionic liquids (RTILs) are solvent with unusual properties, which
      are difficult to characterize experimentally because of their intrinsic
      complexity (large number of atoms, strong Coulomb interactions). Molecular
      simulations have therefore been essential in our understanding of these systems.
      Depending on the target property and on the necessity to account for fine details
      of the molecular structure of the ions, a large range of simulation techniques
      are available. Here I focus on classical molecular dynamics, in which the level
      of complexity of the simulation, and therefore the computational cost, mostly
      depends on the force field. Depending on the representation of the ions, these
      are either classified as all-atom or coarse-grained. In addition, all-atom force
      fields may account for polarization effects if necessary. The most widely used
      methods for RTILs are described together with their main achievements and
      limitations. 

PMID- 25592218
TI  - Muscle dysmorphia: could it be classified as an addiction to body image?
AB  - BACKGROUND: Muscle dysmorphia (MD) describes a condition characterised by a
      misconstrued body image in which individuals who interpret their body size as
      both small or weak even though they may look normal or highly muscular.MD has
      been conceptualized as a type of body dysmorphic disorder, an eating disorder,
      and obsessive-compulsive disorder symptomatology. METHOD AND AIM: Through a
      review of the most salient literature on MD, this paper proposes an alternative
      classification of MD--the 'Addiction to Body Image' (ABI) model--using Griffiths
      (2005)addiction components model as the framework in which to define MD as an
      addiction. RESULTS: It is argued the addictive activity in MD is the maintaining
      of body image via a number of different activities such as bodybuilding,
      exercise,eating certain foods, taking specific drugs (e.g., anabolic steroids),
      shopping for certain foods, food supplements,and the use or purchase of physical
      exercise accessories). In the ABI model, the perception of the positive effects
      on the self-body image is accounted for as a critical aspect of the MD condition
      (rather than addiction to exercise or certain types of eating disorder).
      CONCLUSIONS: Based on empirical evidence to date, it is proposed that MD could be
      re-classified as an addiction due to the individual continuing to engage in
      maintenance behaviours that may cause long-term harm.

PMID- 25592220
TI  - Salivary pooling: is it specific to particular regions in oral submucous
      fibrosis?
AB  - Despite extensive research, the pathophysiology of oral submucous fibrosis
      (OSMF), a premalignant condition that primarily affects the mucosa, is still
      unclear, although the chewing of areca nut is known to be the primary cause.
      While a clear association exists between areca nut and OSMF, very little has been
      published on the reason for its sporadic incidence in the mouth. Many authors
      have suggested the site where quid is habitually placed, but this fails to
      explain multiple sites in those who chew on one side. We hypothesised that the
      pattern of salivary pooling might affect the distribution of OSMF by carrying the
      chemicals responsible for mucosal damage. In our study of 174 patients, we
      evaluated the sites where quid was habitually placed and the areas of salivary
      pooling, and their association with the incidence of OSMF. Most chewers (136/174,
      78%) placed the quid in the buccal vestibule, although other sites were also used
      including the vestibule of the lip, tongue, and floor of the mouth. The
      standardised residuals suggested significant associations (p<0.001) between
      salivary pooling and OSMF, and indicated that salivary pooling affects the
      mucosal surfaces where it occurs. Our results show that the quid is not the only
      cause of OSMF. Salivary pooling also has an important role and provides a
      possible mechanism for the sporadic incidence of the condition. To our knowledge
      this is the first study to evaluate salivary pooling as a contributory factor in
      OSMF, and it may help to explain the pattern of distribution. Further work is
      needed in this area to understand the association more fully.

PMID- 25592221
TI  - Novel technique to secure nasogastric tube in patients with cancer of the head
      and neck.

PMID- 25592222
TI  - Association of single-nucleotide polymorphisms in the IRF6 gene with non
      syndromic cleft lip with or without cleft palate in the Xinjiang Uyghur
      population.
AB  - Our main aim was to investigate the association between the interferon regulatory
      factor (IRF6) gene and non-syndromic cleft lip and palate (nsCLP) in the Xinjiang
      Uyghur population. Twelve single nucleotide polymorphisms (SNP) were screened in
      a group of 100 patients with nsCLP and in a control group of 60 unaffected
      subjects by next generation sequencing using a MiSeq Benchtop Sequencer
      (Illumina). Our case-control association analysis showed that the SNP marker
      rs7545538 differed significantly in genotype (codominant model; CC compared with
      CG compared with GG; p=0.038) and allele frequencies (odds ratio (OR)=1.89, 95%
      CI 1.18-3.03, p=0.007) between patients with nsCLP and controls. Analysis of the
      recessive model of inheritance showed that distribution of the recessive model of
      rs7545538 (GG compared with CC+GC) was significantly higher in patients with
      nsCLP than in controls (OR=2.5, 95% CI 1.13-5.37, p=0.021) and had a borderline
      association with an increased risk of nsCLP (OR=2.5, 95% CI 1.13-5.37, p=0.021).
      Markers rs2235377 and rs2235371 also differed significantly in dominant and over
      dominant models of inheritance (p=0.037) while increased G allele frequency was
      seen in SNP rs2235373 (p=0.03). A haplotype analysis showed four common
      haplotypes in Block 1: CCGGT>CCGAT>CACAT>TAGAC (in frequency). The 5-marker
      combination haplotype CCGAT was significantly more common in patients with nsCLP
      than in controls (p=0.032). In Block 2, the overall distribution of the
      haplotypes TAC and TAG predicted by the three SNP differed significantly between
      the patients with nsCLP and control subjects (p=0.009 and 0.003, respectively).
      Our results showed that genetic polymorphism of the IRF6 gene is associated with
      increased risk of nsCLP in a Xinjiang Uyghur population.

PMID- 25592223
TI  - The boule gene is essential for spermatogenesis of haploid insect male.
AB  - boule (bol), a member of the Deleted in Azoospermia (DAZ) gene family plays an
      important role in meiosis (reductional maturation divisions) in a spermatogenesis
      specific manner in animals by regulating translation of the downstream cell
      division cycle 25 (cdc25) phosphatase mRNA. Orthologues of bol are conserved
      among animals and found in the genomes of hymenopteran insects, in which the
      general mode of reproduction is haplodiploidy: female is diploid and male is
      haploid. In this mode of reproduction, haploid males produce haploid sperm
      through non-reductional maturation divisions. The question thus arises of whether
      the bol gene actually functions during spermatogenesis in these haploid males. In
      this study, we identified two transcriptional isoforms of bol orthologue (Ar bol
      and Ar bol-2), and one cdc25 orthologue (Ar cdc25) in the hymenopteran sawfly,
      Athalia rosae. Ar bol was expressed exclusively in the testis when maturation
      divisions occurred, while Ar bol-2 was expressed ubiquitously. Knockdown of all
      bol transcripts (both Ar bol and Ar bol-2) resulted in a lack of mature sperm,
      whereas males with sole knockdown of Ar bol-2 were able to produce a small number
      of mature sperm. The cell cycle was arrested before maturation divisions in the
      testis in which all bol transcripts were knocked down, as revealed by flow
      cytometry. Although no mature sperm was produced, sperm elongation was partially
      observed when Ar cdc25 alone was knocked down. These results indicate that Ar bol
      is essential for the entry and progression of maturation divisions and sperm
      differentiation in haploid males. 

PMID- 25592224
TI  - The cochlear sensory epithelium derives from Wnt responsive cells in the
      dorsomedial otic cup.
AB  - Wnt1 and Wnt3a secreted from the dorsal neural tube were previously shown to
      regulate a gene expression program in the dorsal otic vesicle that is necessary
      for vestibular morphogenesis (Riccomagno et al., 2005. Genes Dev. 19, 1612-1623).
      Unexpectedly, Wnt1(-/-); Wnt3a(-/-) embryos also displayed a pronounced defect in
      the outgrowth of the ventrally derived cochlear duct. To determine how Wnt
      signaling in the dorsal otocyst contributes to cochlear development we performed
      a series of genetic fate mapping experiments using two independent Wnt responsive
      driver strains (TopCreER and Gbx2(CreER)) that when crossed to inducible
      responder lines (Rosa(lacZ) or Rosa(zsGreen)) permanently labeled dorsomedial
      otic progenitors and their derivatives. Tamoxifen time course experiments
      revealed that most vestibular structures showed some degree of labeling when
      recombination was induced between E7.75 and E12.5, consistent with continuous Wnt
      signaling activity in this tissue. Remarkably, a population of Wnt responsive
      cells in the dorsal otocyst was also found to contribute to the sensory
      epithelium of the cochlear duct, including auditory hair and support cells.
      Similar results were observed with both TopCreER and Gbx2(CreER) strains. The
      ventral displacement of Wnt responsive cells followed a spatiotemporal sequence
      that initiated in the anterior otic cup at, or immediately prior to, the 17
      somite stage (E9) and then spread progressively to the posterior pole of the otic
      vesicle by the 25-somite stage (E9.5). These lineage-tracing experiments identify
      the earliest known origin of auditory sensory progenitors within a population of
      Wnt responsive cells in the dorsomedial otic cup. 

PMID- 25592226
TI  - Loss of cftr function leads to pancreatic destruction in larval zebrafish.
AB  - The development and function of many internal organs requires precisely regulated
      fluid secretion. A key regulator of vertebrate fluid secretion is an anion
      channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Loss of
      CFTR function leads to defects in fluid transport and cystic fibrosis (CF), a
      complex disease characterized by a loss of fluid secretion and mucus buildup in
      many organs including the lungs, liver, and pancreas. Several animal models
      including mouse, ferret and pig have been generated to investigate the
      pathophysiology of CF. However, these models have limited accessibility to early
      processes in the development of CF and are not amenable for forward genetic or
      chemical screens. Here, we show that Cftr is expressed and localized to the
      apical membrane of the zebrafish pancreatic duct and that loss of cftr function
      leads to destruction of the exocrine pancreas and a cystic fibrosis phenotype
      that mirrors human disease. Our analyses reveal that the cftr mutant pancreas
      initially develops normally, then rapidly loses pancreatic tissue during larval
      life, reflecting pancreatic disease in CF. Altogether, we demonstrate that the
      cftr mutant zebrafish is a powerful new model for pancreatitis and pancreatic
      destruction in CF. This accessible model will allow more detailed investigation
      into the mechanisms that drive CF of the pancreas and facilitate development of
      new therapies to treat the disease. 

PMID- 25592228
TI  - Ataxia telangiectasia mutated inhibits oxidative stress-induced apoptosis by
      regulating heme oxygenase-1 expression.
AB  - Ataxia telangiectasia (AT) is caused by mutational inactivation of the ataxia
      telangiectasia mutated (Atm) gene, which is involved in DNA repair. Increased
      oxidative stress has been shown in human AT cells and neuronal tissues of Atm
      deficient mice. Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme and
      protects cells against oxidative stress. The purpose of this study is to
      determine whether ATM induces antioxidant enzyme HO-1 and protects cells from
      oxidative stress-mediated apoptosis by driving the activation of PKC-delta and NF
      kappaB, by increasing cell viability, and by downregulating DNA fragmentation and
      apoptotic indicators (apoptosis-inducing factor and cleaved caspase-3). AT
      fibroblasts stably transfected with human full-length ATM cDNA (YZ5 cells) or the
      empty vector (MOCK cells) were treated with H2O2 as a source of reactive oxygen
      species (ROS). As a result, transfection with ATM inhibited ROS-induced cell
      death and DNA fragmentation in MOCK cells. Transfection with ATM induced
      expression of HO-1 which was mediated by PKC-delta and NF-kappaB in H2O2-treated
      MOCK cells. ZnPP, an HO-1 inhibitor, and transfection with HO-1 siRNA increased
      ROS levels and apoptosis, whereas hemin, an HO-1 activator, reduced ROS levels
      and apoptosis in H2O2-treated YZ5 cells. Rottlerin, a PKC-delta inhibitor,
      inhibited NF-kappaB activation and HO-1 expression in H2O2-treated YZ5 cells.
      MOCK cells showed increased cell death, DNA fragmentation, and apoptotic
      indicators compared to YZ5 cells exposed to H2O2. In addition, transfection with
      p65 siRNA increased ROS levels and DNA fragmentation, but decreased HO-1 protein
      levels in H2O2-treated YZ5 cells. In conclusion, ATM induces HO-1 expression via
      activation of PKC-delta and NF-kappaB and inhibits oxidative stress-induced
      apoptosis. A loss of HO-1 induction may explain why AT patients are vulnerable to
      oxidative stress. 

PMID- 25592225
TI  - Hanging on for the ride: adhesion to the extracellular matrix mediates cellular
      responses in skeletal muscle morphogenesis and disease.
AB  - Skeletal muscle specification and morphogenesis during early development are
      critical for normal physiology. In addition to mediating locomotion, skeletal
      muscle is a secretory organ that contributes to metabolic homeostasis. Muscle is
      a highly adaptable tissue, as evidenced by the ability to increase muscle cell
      size and/or number in response to weight bearing exercise. Conversely, muscle
      wasting can occur during aging (sarcopenia), cancer (cancer cachexia), extended
      hospital stays (disuse atrophy), and in many genetic diseases collectively known
      as the muscular dystrophies and myopathies. It is therefore of great interest to
      understand the cellular and molecular mechanisms that mediate skeletal muscle
      development and adaptation. Muscle morphogenesis transforms short muscle
      precursor cells into long, multinucleate myotubes that anchor to tendons via the
      myotendinous junction. This process requires carefully orchestrated interactions
      between cells and their extracellular matrix microenvironment. These interactions
      are dynamic, allowing muscle cells to sense biophysical, structural,
      organizational, and/or signaling changes within their microenvironment and
      respond appropriately. In many musculoskeletal diseases, these cell adhesion
      interactions are disrupted to such a degree that normal cellular adaptive
      responses are not sufficient to compensate for accumulating damage. Thus, one
      major focus of current research is to identify the cell adhesion mechanisms that
      drive muscle morphogenesis, with the hope that understanding how muscle cell
      adhesion promotes the intrinsic adaptability of muscle tissue during development
      may provide insight into potential therapeutic approaches for muscle diseases.
      Our objectives in this review are to highlight recent studies suggesting
      conserved roles for cell-extracellular matrix adhesion in vertebrate muscle
      morphogenesis and cellular adaptive responses in animal models of muscle
      diseases. 

PMID- 25592227
TI  - Structure and sequence analyses of Bacteroides proteins BVU_4064 and BF1687
      reveal presence of two novel predominantly-beta domains, predicted to be involved
      in lipid and cell surface interactions.
AB  - BACKGROUND: N-terminal domains of BVU_4064 and BF1687 proteins from Bacteroides
      vulgatus and Bacteroides fragilis respectively are members of the Pfam family
      PF12985 (DUF3869). Proteins containing a domain from this family can be found in
      most Bacteroides species and, in large numbers, in all human gut microbiome
      samples. Both BVU_4064 and BF1687 proteins have a consensus lipobox motif
      implying they are anchored to the membrane, but their functions are otherwise
      unknown. The C-terminal half of BVU_4064 is assigned to protein family PF12986
      (DUF3870); the equivalent part of BF1687 was unclassified. RESULTS: Crystal
      structures of both BVU_4064 and BF1687 proteins, solved at the JCSG center, show
      strikingly similar three-dimensional structures. The main difference between the
      two is that the two domains in the BVU_4064 protein are connected by a short
      linker, as opposed to a longer insertion made of 4 helices placed linearly along
      with a strand that is added to the C-terminal domain in the BF1687 protein. The N
      terminal domain in both proteins, corresponding to the PF12985 (DUF3869) domain
      is a beta-sandwich with pre-albumin-like fold, found in many proteins belonging
      to the Transthyretin clan of Pfam. The structures of C-terminal domains of both
      proteins, corresponding to the PF12986 (DUF3870) domain in BVU_4064 protein and
      an unclassified domain in the BF1687 protein, show significant structural
      similarity to bacterial pore-forming toxins. A helix in this domain is in an
      analogous position to a loop connecting the second and third strands in the toxin
      structures, where this loop is implicated to play a role in the toxin insertion
      into the host cell membrane. The same helix also points to the groove between the
      N- and C-terminal domains that are loosely held together by hydrophobic and
      hydrogen bond interactions. The presence of several conserved residues in this
      region together with these structural determinants could make it a functionally
      important region in these proteins. CONCLUSIONS: Structural analysis of BVU_4064
      and BF1687 points to possible roles in mediating multiple interactions on the
      cell-surface/extracellular matrix. In particular the N-terminal domain could be
      involved in adhesive interactions, the C-terminal domain and the inter-domain
      groove in lipid or carbohydrate interactions.

PMID- 25592229
TI  - In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors
      using the novel radiotracer (68)Ga-NOTA-c(NGR).
AB  - PURPOSE: Aminopeptidase N (APN/CD13) plays an important role in tumor
      neoangiogenic process and the development of metastases. Furthermore, it may
      serve as a potential target for cancer diagnosis and therapy. Previous studies
      have already shown that asparagine-glycine-arginine (NGR) peptides specifically
      bind to APN/CD13. The aim of the study was to synthesize and investigate the
      APN/CD13 specificity of a novel (68)Ga-labeled NOTA-c(NGR) molecule in vivo using
      miniPET. METHODS: c[KNGRE]-NH2 peptide was conjugated with p-SCN-Bn-NOTA and was
      labeled with Ga-68 ((68)Ga-NOTA-c(NGR)). Orthotopic and heterotopic transplanted
      mesoblastic nephroma (NeDe) bearing Fischer-344 rats were prepared, on which
      biodistribution studies and miniPET scans were performed for both (68)Ga-NOTA
      c(NGR) and alphanubeta3 integrin selective (68)Ga-NODAGA-[c(RGD)]2 tracers.
      APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by
      western blot. RESULTS: (68)Ga-NOTA-c(NGR) was produced with high specific
      activity (5.13-5.92GBq/MUmol) and with excellent radiochemical purity (95%<), at
      all cases. Biodistribution studies in normal rats showed that uptake of the
      (68)Ga-NOTA-c(NGR) was significantly (p?0.05) lower in abdominal organs in
      comparison with (68)Ga-NODAGA-[c(RGD)]2. Both radiotracers were mainly excreted
      from the kidney. In NeDe tumor bearing rats higher (68)Ga-NOTA-c(NGR)
      accumulation was found in the tumors than that of the (68)Ga-NODAGA-[c(RGD)]2.
      Using orthotopic transplantation, metastases were developed which showed specific
      (68)Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of
      APN/CD13 expression in NeDe tumors and metastases. CONCLUSION: Our novel
      radiotracer (68)Ga-NOTA-c(NGR) showed specific binding to the APN/CD13 expressed
      ortho- and heterotopic transplanted NeDe tumors. Therefore, (68)Ga-NOTA-c(NGR) is
      a suitable tracer for the detection of APN/CD13 positive tumors and metastases in
      vivo.

PMID- 25592230
TI  - Suppression of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to
      the sensitization of dorsal horn WDR neurons and pain hypersensitivity in a rat
      model of bone cancer pain.
AB  - Primary and metastatic cancers that affect bones are frequently associated with
      severe and intractable pain. The mechanisms underlying the development of bone
      cancer pain are largely unknown. In the present study, we investigated whether
      inhibition of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to
      the development of bone cancer pain via sensitization of dorsal horn wide dynamic
      range (WDR) neurons. Using a rat model of bone cancer pain based on intratibial
      injection of MRMT-1 tumor cells, we observed a significant increase in C-fiber
      responses of dorsal horn WDR neurons in the MRMT-1 injected rats, indicating
      sensitization of spinal WDR neurons in bone cancer rats. Furthermore, we
      discovered that blockade of KCNQ/M channels in the spinal cord by local
      administration of XE-991, a specific KCNQ/M channel blocker, caused a robust
      increase in excitability of dorsal horn WDR neurons, while, producing obvious
      pain hypersensitivity in normal rats. On the contrary, activation of spinal
      KCNQ/M channels by retigabine, a selective KCNQ/M channel opener, not only
      inhibited the bone cancer-induced hyperexcitability of dorsal horn WDR neurons,
      but also alleviated mechanical allodynia and thermal hyperalgesia in the bone
      cancer rats, while all of these effects of retigabine could be blocked by KCNQ/M
      channel antagonist XE-991. All things considered, these results suggest that
      suppression of KCNQ/M channels in the spinal cord likely contributes to the
      development of bone cancer pain via sensitization of dorsal horn WDR neurons in
      rats following tumor cell inoculation.

PMID- 25592232
TI  - Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation,
      metastatic potential and survival under metabolic stress.
AB  - BACKGROUND: Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has
      been reported in pancreatic cancer. However, the role of NNMT in pancreatic
      cancer development remains elusive. Therefore, the present study was to
      investigate the impact of NNMT on pancreatic cancer cell proliferation,
      metastatic potential and survival under metabolic stress. METHODS: Pancreatic
      cancer cell line PANC-1 was transfected with NNMT expression plasmid or small
      interfering RNA of NNMT to overexpress or knockdown intracellular NNMT
      expression, respectively. Rate of cell proliferation was monitored. Transwell
      migration and matrigel invasion assays were conducted to assess cell migration
      and invasion capacity. Resistance to glucose deprivation, sensitivity to
      glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were
      examined to evaluate cell survival under metabolic stress. RESULTS: NNMT
      silencing markedly reduced cell proliferation, whereas NNMT overexpression
      promoted cell growth moderately. Knocking down NNMT also significantly suppressed
      the migration and invasion capacities of PANC-1 cells. Conversely, NNMT
      upregulation enhanced cell migration and invasion capacities. In addition, NNMT
      knockdown cells were much less resistant to glucose deprivation and rapamycin as
      well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed
      opposite effects although the effects were not so striking. CONCLUSIONS: These
      data sugguest that NNMT plays an important role in PANC-1 cell proliferation,
      metastatic potential and survival under metabolic stress.

PMID- 25592231
TI  - Association between Chloroplast and Mitochondrial DNA sequences in Chinese Prunus
      genotypes (Prunus persica, Prunus domestica, and Prunus avium).
AB  - BACKGROUND: The nuclear DNA is conventionally used to assess the diversity and
      relatedness among different species, but variations at the DNA genome level has
      also been used to study the relationship among different organisms. In most
      species, mitochondrial and chloroplast genomes are inherited maternally;
      therefore it is anticipated that organelle DNA remains completely associated.
      Many research studies were conducted simultaneously on organelle genome. The
      objectives of this study was to analyze the genetic relationship between
      chloroplast and mitochondrial DNA in three Chinese Prunus genotypes viz., Prunus
      persica, Prunus domestica, and Prunus avium. RESULTS: We investigated the genetic
      diversity of Prunus genotypes using simple sequence repeat (SSR) markers relevant
      to the chloroplast and mitochondria. Most of the genotypes were genetically
      similar as revealed by phylogenetic analysis. The Y2 Wu Xing (Cherry) and L2 Hong
      Xin Li (Plum) genotypes have a high similarity index (0.89), followed by Zi Ye Li
      (0.85), whereas; L1 Tai Yang Li (plum) has the lowest genetic similarity (0.35).
      In case of cpSSR, Hong Tao (Peach) and L1 Tai Yang Li (Plum) genotypes
      demonstrated similarity index of 0.85 and Huang Tao has the lowest similarity
      index of 0.50. The mtSSR nucleotide sequence analysis revealed that each genotype
      has similar amplicon length (509 bp) except M5Y1 i.e., 505 bp with CCB256 primer;
      while in case of NAD6 primer, all genotypes showed different sizes. The MEHO
      (Peach), MEY1 (Cherry), MEL2 (Plum) and MEL1 (Plum) have 586 bps; while MEY2
      (Cherry), MEZI (Plum) and MEHU (Peach) have 585, 584 and 566 bp, respectively.
      The CCB256 primer showed highly conserved sequences and minute single polymorphic
      nucleotides with no deletion or mutation. The cpSSR (ARCP511) microsatellites
      showed the harmonious amplicon length. The CZI (Plum), CHO (Peach) and CL1 (Plum)
      showed 182 bp; whileCHU (Peach), CY2 (Cherry), CL2 (Plum) and CY1 (Cherry) showed
      181 bp amplicon lengths. CONCLUSIONS: These results demonstrated high
      conservation in chloroplast and mitochondrial genome among Prunus species during
      the evolutionary process. These findings are valuable to study the organelle DNA
      diversity in different species and genotypes of Prunus to provide in depth
      insight in to the mitochondrial and chloroplast genomes.

PMID- 25592234
TI  - Genetic variability of DNA repair mechanisms and glutathione-S-transferase genes
      influences treatment outcome in osteosarcoma.
AB  - BACKGROUND: Osteosarcoma patients are commonly treated with cisplatin-based
      preoperative and postoperative chemotherapy. Cisplatin binds to DNA and forms
      both intrastrand and interstrand crosslinks, inhibiting DNA replication.
      Glutathione-S-transferases (GSTs) participate in cisplatin detoxification, while
      several independent DNA repair mechanisms repair cisplatin-induced lesions. The
      aim of our study was to investigate the influence of genetic variability of DNA
      repair mechanisms and GSTs on efficacy and toxicity of cisplatin-based
      chemotherapy in osteosarcoma patients. METHODS: A total of 66 osteosarcoma
      patients were genotyped for ERCC1, ERCC2, NBN, RAD51, XRCC3, and GSTP1
      polymorphisms, as well as GSTM1 and GSTT1 gene deletion. We determined the
      influence of polymorphisms on survival and treatment outcome using Cox regression
      and logistic regression. RESULTS: Carriers of at least one polymorphic ERCC2
      rs1799793 allele had longer event-free survival (EFS) (P=0.006; hazard ratio
      (HR)=0.28; 95% confidence interval (CI)=0.11-0.70). Polymorphic GSTP1 rs1138272
      allele was associated with both shorter EFS and OS (P=0.005; HR=3.67; 95%CI=1.47
      9.16; and P=0.004; HR=3.52; 95%CI=1.51-8.22, respectively). Compared to the
      reference NBN CAA haplotype, NBN CGA haplotype was associated with shorter EFS
      (P=0.001; HR=4.12; 95%CI=1.77-9.56). CONCLUSIONS: Our results suggest that DNA
      repair polymorphisms and GST polymorphisms could be used as predictive factors
      for cisplatin-based chemotherapy in osteosarcoma patients and could contribute to
      treatment personalization.

PMID- 25592233
TI  - The number of circulating monocytes as biomarkers of the clinical response to
      methotrexate in untreated patients with rheumatoid arthritis.
AB  - BACKGROUND: The aim of this work was to analyze the number and distribution of
      circulating monocytes, and of their CD14(+high)CD16(-), CD14(+high)CD16(+) and
      CD14(+low)CD16(+) subset cells, in treatment-naive patients with rheumatoid
      arthritis (RA), and to determine their value in predicting the clinical response
      to methotrexate (MTX) treatment. METHODS: This prospective work investigated the
      number of circulating monocytes, and the numbers of CD14(+high)CD16(-),
      CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in 52 untreated patients
      with RA before MTX treatment, and at 3 and 6 months into treatment, using flow
      cytometry. RESULTS: The absolute number of circulating monocytes, and the numbers
      of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells,
      were significantly higher in MTX non-responders than in responders and healthy
      controls before starting and throughout treatment. Responders showed normal
      numbers of monocytes, and of their subset cells, over the study period. The pre
      treatment absolute number of circulating monocytes, and the numbers of
      CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, were found to be
      predictive of the clinical response to MTX, with a sensitivity and specificity of
      >70% and >88%, respectively. CONCLUSIONS: Treatment-naive patients with RA showed
      an anomalous distribution of circulating monocyte subsets, and an anomalous
      number of cells in each subset. A higher pre-treatment number of circulating
      monocytes, and higher numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset
      cells, predict a reduced clinical response to MTX in untreated patients with RA.

PMID- 25592235
TI  - A prospective evaluation of C-peptide levels and colorectal adenoma incidence.
AB  - BACKGROUND: Obesity is a recognised positive risk factor for colorectal adenoma
      and colorectal cancer. Obesity is associated with insulin resistance and
      compensatory hyperinsulinaemia, and circulating insulin and C-peptide, a
      biomarker of insulin levels, have been positively associated with colorectal
      cancer risk. However, whether a similar relationship exists for colorectal
      adenomas, an established colorectal cancer precursor, is unclear. METHODS: In a
      nested case-control study of 273 colorectal adenoma cases and 355 matched
      controls from the screening arm of the Prostate, Lung, Colorectal and Ovarian
      Cancer Screening Trial, serum C-peptide levels were measured by a
      chemiluminescent immunometric assay. Multivariable unconditional logistic
      regression models were used to calculate odds ratios (OR) and 95% confidence
      intervals (CI) for colorectal adenoma within quartiles of C-peptide. Further, to
      explore the temporal stability of C-peptide, repeat samples from the incident
      adenoma cases (n=50) and controls (n=30), over a 5-year period were assayed and
      the intra-class correlations (ICC) estimated. RESULTS: In a multivariable model
      that included established colorectal adenoma risk factors, C-peptide levels were
      not associated with colorectal adenoma (Q4 vs. Q1, OR 0.83, 95% CI: 0.52-1.31; P
      trend 0.32); similar null associations were observed by gender, by adenoma
      subsite and for advanced adenomas. Among control participants, the ICC value over
      a 5-year period was 0.66. CONCLUSION: Our results suggest that higher C-peptide
      levels were not associated with colorectal adenoma incidence in this study
      population. Other biological pathways associated with obesity may be more
      relevant to the early stages of colorectal tumorigenesis.

PMID- 25592236
TI  - My approach to patients with heart failure and a normal ejection fraction.

PMID- 25592237
TI  - My approach to Wolff-Parkinson-White syndrome.

PMID- 25592238
TI  - My approach to aortic stenosis.

PMID- 25592239
TI  - Ascending KLFs in cardiovascular biology.

PMID- 25592240
TI  - My approach to stable thoracic aortic aneurysm.

PMID- 25592241
TI  - The Metabolic Risk in Patients Newly Diagnosed with Acromegaly Is Related to Fat
      Distribution and Circulating Adipokines and Improves after Treatment.
AB  - BACKGROUND/AIMS: Adipose tissue (AT) distribution is closely related to metabolic
      disease risk. Growth hormone (GH) reduces visceral and total body fat mass and
      induces whole-body insulin resistance. Our aim was to assess the effects of total
      and visceral AT (VAT) distribution and derived adipokines on systemic insulin
      resistance and lipid metabolism in acromegaly. METHODS: Seventy adult patients
      with active acromegaly (43 males, age 49 +/- 14 years) were evaluated before
      treatment, and a subset (n = 30, 20 males) was evaluated after treatment for
      acromegaly. Body composition and VAT, glucose metabolism parameters, lipids, C
      reactive protein, and selected adipokines (vaspin, omentin, adiponectin, and
      leptin) were measured. RESULTS: At baseline, VAT was positively associated with
      glucose metabolism parameters and with lipids. GH, but not IGF-I, was negatively
      associated with all AT depots (visceral, trunk, limbs, and total; 0.41 <= r <=
      0.61, p < 0.001 for all) and positively associated with vaspin (r = 0.31, p =
      0.013). The fat deposition after treatment was predominantly located on trunk and
      visceral depots. The lipid profile partially improved, with increases in HDL and
      apolipoprotein A-I and a decrease in lipoprotein(a). Vaspin decreased and omentin
      increased. Adiponectin and leptin did not change significantly. The improvement
      in homeostasis model assessment for insulin resistance (HOMA-IR) was best
      predicted by the decreases in IGF-I and vaspin and the lack of an increase in
      trunk fat (R2 = 0.59, p = 0.001). CONCLUSIONS: (1) VAT is a metabolic risk factor
      for patients with active acromegaly; (2) vaspin and omentin levels are influenced
      by the disease activity but are not associated with VAT mass; (3) fat deposition
      after treatment occurs predominantly on the trunk and in visceral depots, and (4)
      insulin resistance decreases and the lipid profile partially improves with
      treatment.

PMID- 25592242
TI  - A meta-analysis examining the use of fibrin glue mesh fixation versus suture mesh
      fixation in open inguinal hernia repair.
AB  - BACKGROUND: The aim of this study was to systematically analyze the randomized
      trials comparing fibrin glue mesh fixation with suture mesh fixation in open
      inguinal hernia repair. METHODS: Information was collected from a literature
      search using PubMed, Springer, Cochrane Library database and reference lists. The
      methodological quality of included publications was evaluated. Statistical
      analysis was performed using Review Manager Version 5.2.5 software. RESULTS: Nine
      articles were identified for inclusion: four randomized controlled trials (RCTs)
      and five prospective observational clinical studies. All the trials were
      considered to be of fair quality. The results showed that there was a lower
      incidence of chronic pain (RR 0.42, 95% CI 0.22-0.79, I(2) 11%; p < 0.01), and
      hematoma/seroma (RR 0.43, 95% CI 0.21-0.87, I(2) 0%; p < 0.05) in the fibrin glue
      mesh fixation group. However, the results of meta-analysis revealed that the
      incidence of recurrence or urinary problems between the two procedures were
      similar. CONCLUSIONS: During the 6-15 months follow-up, fibrin glue mesh fixation
      is a feasible alternative for mesh fixation with sutures in open inguinal hernia
      repair. However, the poor quality of the included trials limits the evidence;
      rigorously designed trials are warranted to confirm this conclusion.

PMID- 25592243
TI  - Persistent severe hypereosinophilic asthma is not associated with airway
      remodeling.
AB  - Hypereosinophilic asthma (HEA) is considered as a specific severe asthma
      phenotype. Whether eosinophils have a link with airway remodeling characterized
      by pathological (thickening of the basement membrane), functional (persistent
      airflow impairment and decline in lung function) and imaging features (increase
      airway wall thickness at CT scan) is still debated. In a one year prospective
      cohort of 142 severe asthma patients (according to IMI), 14 persistent HEA
      patients (defined by a persistent blood eosinophilia >500/mm(3) at two
      consecutive visits) were identified and compared with ten patients without any
      blood eosinophilia during the follow-up period (NEA, blood eosinophilia always
      <500/mm(3)). Airflow and lung volumes were recorded. Bronchial biopsies obtained
      at enrollment were stained for eosinophils (EG2) and basement membrane thickness
      (BM) was quantified. Imaging by CT scan acquisition was standardized and
      bronchial abnormalities quantified. ACQ score and exacerbations were
      prospectively recorded. HEA was not associated with preeminent features of airway
      remodeling assessed by airflow impairment (Best ever FEV1 values 97% +/- 20 in
      HEA vs. 80 +/- 24% in NEA, p = 0.020), decline of FEV1 (FEV1 Decline 40 +/- 235
      ml/y in HEA vs. 19 +/- 40 ml/y in NEA, P = 0.319), submucosal abnormalities (BM
      thickness 7.80 +/- 2.66 MUm in HEA vs. 6.84 +/- 2.59 in NEA, p = 0.37) and airway
      wall thickening at CT-scan (0.250 +/- 0.036 mm vs. 0.261 +/- 0.043, p = 0.92).
      Eosinophils blood count was inversely correlated with semiquantitative imaging
      score (rho -0.373, p = 0.039). Smoking history and positive skin prick tests were
      independent risk factors for increased BM thickening. Outcomes were similar in
      both populations (Control and exacerbations). Persistent HEA is not associated
      with evidences of airway remodeling. 

PMID- 25592244
TI  - Real-life effectiveness of smoking-cessation treatments in general practice
      clinics in Denmark. The Escape Smoke project.
AB  - BACKGROUND: The smoking prevalence has not decreased in the last years in
      Denmark. General practice (GP) offers smoking cessation (SC) treatment. Studies
      of real-life effectiveness of daily practice SC-activities from the GP-setting
      opposed to efficacy results from randomized clinical trials are few. The study
      aim was to evaluate the real-life effectiveness of SC-treatments for daily
      smokers among Danish GP-clinics. METHODS: In a multi-centre-based observational
      study design Danish GP-clinics with prior SC-activity recruited daily smokers
      motivated for quitting. As per usual clinical practice SC-medicine could be
      nicotine replacement therapy (NRT), prescription-based SC-medicine (varenicline
      or bupropion) or no medicine. The primary endpoint was percentage of patients
      remaining abstinent 6 months after the quit date (ITT, self-reported continuous
      abstinence). RESULTS: Forty GP-clinics recruited 515 (273 females, 20% COPD)
      daily smokers being moderately nicotine dependent and heavy smoking (19
      cigarettes/day). Receiving intensive advice, 74% did use SC-medicine paid out-of
      pocket (1/3 NRT and 2/3 prescription-based). After 6 months, 187 participants had
      remained abstinent (36%). Adjusted for potential confounding the use of
      prescription-based SC-medicine plus counseling was associated with significantly
      doubling the chance of staying abstinent after 6 months as compared to no SC
      medicine (OR: 1.97). This association could not be found for NRT. Being male and
      using prescription-based SC-medicine were independent significant predictors for
      long-term abstinence. CONCLUSIONS: Smoking cessation in Danish GP-clinics with
      some prior SC-activity can result in rather high long-term quit rates, especially
      when combining counseling and prescription-based SC-medicine. The effectiveness
      of prescription-based SC-medications versus NRT in the general population merits
      further investigation.

PMID- 25592246
TI  - hTERT-immortalized ovine microglia propagate natural scrapie isolates.
AB  - Ex vivo propagation of natural prion isolates (i.e., propagated solely in the
      natural host) is crucial for the characterization and study of transmissible
      spongiform encephalopathies (TSEs). Several well-established, prion-permissive
      cell culture systems are available; however, only a few cell lines are permissive
      to natural prion isolates and these cells are not pathophysiologically relevant
      (e.g., renal epithelium and fibroblast-like cells). Therefore, a
      pathophysiologically relevant cell line derived from a natural TSE host could be
      used for propagation of natural prion isolates. In this study, ovine brain
      macrophages (microglia) were immortalized by transfection with the human
      telomerase reverse transcriptase (hTERT) gene to identify cell lines (hTERT
      microglia) permissive to natural scrapie prion isolates. Following transfection,
      hTERT-microglia were passaged up to 100 times and their lifespan was
      significantly longer compared to parental cells (Fisher's exact test, P<0.001).
      Multiple sublines were permissive to cell culture-adapted prions; two sublines
      were also permissive to natural scrapie isolates (i.e., derived from brain
      homogenates of sheep infected with scrapie). Prion infectivity and partial
      protease resistance of the prion protein were maintained in hTERT-microglia.
      Comparisons between scrapie-permissive and non-permissive hTERT-microglia
      sublines revealed that overall quantity of the normal cellular prion protein was
      not associated with prion permissiveness. The use of hTERT-microglia in future
      TSE studies may be more germane to the characterization of the cellular and
      subcellular pathophysiology of natural scrapie prion isolates and to investigate
      host-specific factors involved in prion replication. 

PMID- 25592247
TI  - Down syndrome and nonautoimmune hypothyroidisms in neonates and infants.
AB  - Down syndrome is characterized by a high prevalence of thyroid dysfunction during
      childhood. In this paper, we review the different kinds of thyroid dysfunction
      that occur excluding those of autoimmune origin: congenital hypothyroidism
      (elevated plasma TSH with low plasma T4 occurring at birth usually detected by
      neonatal screening), subclinical hypothyroidism (elevated plasma TSH with plasma
      T4 in the normal range, which can be congenital or acquired) and acquired primary
      hypothyroidism (elevated plasma TSH and low plasma T4 occurring after birth).
      These dysfunctions, while not due to autoimmunity, are of thyroidal origin.
      However, the mechanisms leading to these different thyroidal abnormalities have
      not been clearly defined; in particular, it is difficult to determine whether the
      different types of dysfunction have a common cause, or if the causes are
      distinct. Treatment is prescribed according to the type of thyroidal abnormality.

PMID- 25592248
TI  - Retinaldehyde dehydrogenase activity is triggered during allograft rejection and
      it drives Th1/Th17 cytokine production.
AB  - Retinoic acid (RA), a vitamin A metabolite, has been attributed to relevant
      functions in adaptive immunity. On T cells, the disruption on RA signaling alters
      both CD4+ and CD8+ T cells effector function. In this study, we evaluated the
      contribution of RA synthesis during the immune response using an in vivo skin
      transplantation model. Our data indicates that the frequency and number of cells
      containing an active retinaldehyde dehydrogenase (RALDH), a key enzyme for RA
      synthesis, is increased during skin transplant rejection. In addition, we found
      that the expression of the mRNA coding for the isoform RALDH2 is up-regulated on
      graft rejecting draining lymph nodes (dLNs) cells. Lastly, we observed that IFN
      gamma and IL-17 production by ex vivo re-stimulated dLNs cells is greatly
      increased during rejection, which it turns depends on RA synthesis, as shown in
      experiments using a specific RALDH inhibitor. Altogether, our data demonstrate
      that RA synthesis is incremented during the immune response against an allograft,
      and also indicates that the synthesis of RA is required for cytokine production
      by dLNs resident T cells. 

PMID- 25592249
TI  - Patient-specific scatter correction for flat-panel detector-based cone-beam CT
      imaging.
AB  - A patient-specific scatter correction algorithm is proposed to mitigate scatter
      artefacts in cone-beam CT (CBCT). The approach belongs to the category of
      convolution-based methods in which a scatter potential function is convolved with
      a convolution kernel to estimate the scatter profile. A key step in this method
      is to determine the free parameters introduced in both scatter potential and
      convolution kernel using a so-called calibration process, which is to seek for
      the optimal parameters such that the models for both scatter potential and
      convolution kernel is able to optimally fit the previously known coarse estimates
      of scatter profiles of the image object. Both direct measurements and Monte Carlo
      (MC) simulations have been proposed by other investigators to achieve the
      aforementioned rough estimates. In the present paper, a novel method has been
      proposed and validated to generate the needed coarse scatter profile for
      parameter calibration in the convolution method. The method is based upon an
      image segmentation of the scatter contaminated CBCT image volume, followed by a
      reprojection of the segmented image volume using a given x-ray spectrum. The
      reprojected data is subtracted from the scatter contaminated projection data to
      generate a coarse estimate of the needed scatter profile used in parameter
      calibration. The method was qualitatively and quantitatively evaluated using
      numerical simulations and experimental CBCT data acquired on a clinical CBCT
      imaging system. Results show that the proposed algorithm can significantly reduce
      scatter artefacts and recover the correct CT number. Numerical simulation results
      show the method is patient specific, can accurately estimate the scatter, and is
      robust with respect to segmentation procedure. For experimental and in vivo human
      data, the results show the CT number can be successfully recovered and anatomical
      structure visibility can be significantly improved. 

PMID- 25592245
TI  - Initiation of protein-primed picornavirus RNA synthesis.
AB  - Plus strand RNA viruses use different mechanisms to initiate the synthesis of
      their RNA chains. The Picornaviridae family constitutes a large group of plus
      strand RNA viruses that possess a small terminal protein (VPg) covalently linked
      to the 5'-end of their genomes. The RNA polymerases of these viruses use VPg as
      primer for both minus and plus strand RNA synthesis. In the first step of the
      initiation reaction the RNA polymerase links a UMP to the hydroxyl group of a
      tyrosine in VPg using as template a cis-replicating element (cre) positioned in
      different regions of the viral genome. In this review we will summarize what is
      known about the initiation reaction of protein-primed RNA synthesis by the RNA
      polymerases of the Picornaviridae. As an example we will use the RNA polymerase
      of poliovirus, the prototype of Picornaviridae. We will also discuss models of
      how these nucleotidylylated protein primers might be used, together with viral
      and cellular replication proteins and other cis-replicating RNA elements, during
      minus and plus strand RNA synthesis. 

PMID- 25592250
TI  - Airway compromise in children exposed to single-use laundry detergent pods: a
      poison center observational case series.
AB  - INTRODUCTION: Single-use laundry detergent pods (LDPs) were introduced to the
      United States in 2010 but had been available in Europe as early as 2001. Case
      reports of unintentional exposures noted vomiting, ocular injuries, respiratory
      depression, and central nervous system depression. We summarize clinical effects
      from unintentional LDP exposures reported to a single poison center over 15
      months. METHODS: Electronic poison center records were searched using verbatim
      field and both product and generic codes to identify laundry pod exposures from
      January 1, 2012, through April 9, 2013. Clinical effects were abstracted to a
      database and summarized using descriptive statistics. RESULTS: We identified 131
      cases between March 2012 and April 2013. Median (interquartile range) age was 2.0
      (1.5) years with 4 adult cases; all were coded as unintentional. The most common
      route was ingestion (120) followed by ocular (14) and dermal (6). Some patients
      had multiple routes of exposure. Of ingestion exposures, 79 (66%) were managed at
      home; and 41 (34%) were evaluated in a hospital, of which 9 patients were
      admitted. The median (interquartile range) age of admitted patients was 1.4 (1.1)
      years. Relevant findings in these admitted children included emesis (78%),
      central nervous system depression (22%), upper airway effects (56%), lower
      respiratory symptoms (33%), seizure (n = 1), and intubation (67%). One child with
      emesis initially managed at home was subsequently intubated for respiratory
      distress. DISCUSSION: Exposure to LDP can cause significant toxicity,
      particularly in infants and toddlers. Compared to traditional detergents,
      clinicians should be aware of the potential for airway compromise following
      exposure to LDP.

PMID- 25592251
TI  - Evaluation of acid-base status in patients admitted to ED-physicochemical vs
      traditional approaches.
AB  - BACKGROUND: The aim of this study is to evaluate the value of physicochemical,
      base excess (BE), and plasma bicarbonate concentration ([HCO3(-)]) approaches on
      the assessment of acid-base status in patients presented to the emergency
      department (ED). METHODS: Upon presentation at ED, patients whose arterial blood
      was deemed in need of analysis were studied. Arterial blood gases, serum
      electrolytes, and proteins were measured and used to derive [HCO3(-)], BE, anion
      gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap
      (SIG) and SIG corrected for water excess/deficit (SIGcor). In each patient the
      acid-base status was evaluated using the BE, [HCO3(-)], and physicochemical
      approaches. RESULTS: A total of 365 patients were studied. Compared with BE (n =
      202) and [HCO3(-)] (n = 151), physicochemical approach (n = 279) identified
      significantly more patients with metabolic acid-base disturbances (P < .0001).
      Significantly fewer patients with unmeasured anions acidosis were identified with
      AGadj than with SIGcor (164 vs 230; P < .0001). On the basis of BE, 75 patients
      had normal acid-base balance, and 65 (87%) of them exhibited at least 1 hidden
      acid-base disturbance, identified by the physicochemical approach. The
      corresponding values with [HCO3(-)] approach were 108 and 95 (88%) patients. When
      patients with high AGadj were excluded, 44 patients with BE and 67 with [HCO3(-)]
      approach had normal acid-base status, and most of them exhibited at least 1 acid
      base disturbance with the physicochemical approach, whereas 12 and 21 patients,
      respectively, had high SIGcor. CONCLUSION: Compared with the BE and [HCO3(-)]
      methods, the physicochemical approach has a better diagnostic accuracy to
      identify metabolic acid-base disturbances.

PMID- 25592252
TI  - Anterior chamber depth measurement using ultrasound to assess elevated
      intraocular pressure.
AB  - Increased anterior chamber pressure also known as intraocular pressure can result
      from conditions such as glaucoma and trauma. The pressure in the anterior chamber
      is measured using tonometer. Measurement of the intraocular pressure is
      essential, as it requires immediate medical attention to alleviate pain and to
      avoid temporary or permanent damage to intraocular structures. Bedside ocular
      ultrasound (US) has gained popularity in recent years. It has been used to assess
      intracranial pressure via optic nerve sheath diameter (ONSD) and evaluate retinal
      detachment, vitreous hemorrhage, or pupillary reflex in a trauma patient. We
      report 2 cases of patients with glaucoma and a case of a patient with trauma to
      the eye with swelling. Anterior chamber depth measurement was conducted and
      compared with measurements of intraocular pressure (IOP) using a tonometer.

PMID- 25592253
TI  - Social interaction and cocaine conditioning in mice increase spontaneous spike
      frequency in the nucleus accumbens or septal nuclei as revealed by multielectrode
      array recordings.
AB  - Both cocaine and social interaction place preference conditioning lead to
      increased neuronal expression of the immediate early gene EGR1 in the nucleus
      accumbens, a central region of the reward pathway, suggesting that both drug and
      natural rewards may be processed in similar brain regions. In order to gain novel
      insights into the intrinsic in vitro electrical activity of the nucleus accumbens
      and adjacent brain regions and to explore the effects of reward conditioning on
      network activity, we performed multielectrode array recordings of spontaneous
      firing in acute brain slices of mice conditioned to either cocaine or social
      interaction place preference. Cocaine conditioning increased the spike frequency
      of neurons in the septal nuclei, whereas social interaction conditioning
      increased the spike frequency in the nucleus accumbens compared to saline control
      animals. In addition, social interaction conditioning decreased the amount of
      active neuron clusters in the nucleus accumbens. Our findings suggest that place
      preference conditioning for both drug and natural rewards may induce persistent
      changes in neuronal network activity in the nucleus accumbens and the septum that
      are still preserved in acute slice preparations.

PMID- 25592255
TI  - Isolation and identification of a high molecular weight protein in sow milk.
AB  - A high molecular weight protein (HMWP) was isolated and purified from sow milk,
      and some of its biochemical characteristics and biological functions were
      identified. The origin of HMWP was also investigated. The molecular weight of
      HMWP was determined to be about 115 000 and 114 800 by SDS-PAGE and gel
      filtration, respectively. The sequence of 10 amino acids in N-terminal of HMWP
      was Ala-Leu-Val-Gln-Ser-Cys-Leu-Asn-Leu-Val. The sequence was blasted against
      GenBank. No protein showed significant similarity with this sequence suggesting
      the HMWP may be novel. The result of liquid chromatography mass spectrometry (LC
      MS) also proved HMWP could be a novel protein. By amino acid assay, HMWP was rich
      in glutamate (including glutamine), cysteine, glycine, aspartic acid (including
      asparagines) and proline. The content of hydrophobic amino acids (Ala, Val, Leu,
      Ile, Met, Phe and Pro) was lower at 18.59% of the total amino acids suggesting
      HMWP has high solubility in water. Western blots of lectins were used to identify
      the kinds of carbohydrate residues attached to HMWP qualitatively. The result
      showed that HMWP was a kind of glycoprotein containing N-acetylneuraminic acid
      (NeuNAc), mannose (Man) and/or N-acetylglucosamine (GlcNAc). By isoelectric
      focusing, HMWP pI was found to be 5.1. Compared with milk fat globule membrane
      protein (MFGMP) isolated from the sow milk in SDS-PAGE, MFGMP did not contain
      HMWP. HMWP was assumed to be a secretory milk protein. HMWP was not found in
      bovine, goat, rabbit or human milk in SDS-PAGE gel suggesting HMWP may be unique
      to sow milk. By Western blot, HMWP could be detected in sow milk, not in sow
      serum, which suggests it is synthesized and secreted by the mammary gland. HMWP
      concentrations in sows milk were the lowest in the first day of lactation, rose
      significantly during lactation 1 to 7 days. The HMWP content of sows milk
      remained relatively constant ((1.95+/-0.13) g/l) during lactation 7 to 20 days.
      HMWP significantly inhibited Escherichia coli in a dose related manner in vitro.
      Overall, HMWP could be a novel sow milk protein with implications for the mammary
      gland and the piglet. 

PMID- 25592254
TI  - Safe and efficacious artemisinin-based combination treatments for African
      pregnant women with malaria: a multicentre randomized control trial.
AB  - BACKGROUND: Asymptomatic and symptomatic malaria during pregnancy has
      consequences for both mother and her offspring. Unfortunately, there is
      insufficient information on the safety and efficacy of most antimalarials in
      pregnancy. Indeed, clinical trials assessing antimalarial treatments
      systematically exclude pregnancy for fear of teratogenicity and embryotoxicity.
      The little available information originates from South East Asia while in sub
      Saharan Africa such information is still limited and needs to be provided.
      DESIGN: A Phase 3, non-inferiority, multicentre, randomized, open-label clinical
      trial on safety and efficacy of 4 ACT when administered during pregnancy was
      carried out in 4 African countries: Burkina Faso, Ghana, Malawi and Zambia. This
      is a four arm trial using a balanced incomplete block design. Pregnant women
      diagnosed with malaria are randomised to receive either amodiaquine-artesunate
      (AQ-AS), dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine (AL),
      or mefloquine-artesunate (MQAS). They are actively followed up until day 63 post
      treatment and then monthly until 4-6 weeks post-delivery. The offspring is
      visited at the time of the first birthday. The primary endpoint is treatment
      failure (PCR adjusted) at day 63 and safety profiles. Secondary endpoints
      included PCR unadjusted treatment failure up to day 63, gametocyte carriage, Hb
      changes, placenta malaria, mean birth weight and low birth weight. The primary
      statistical analysis will use the combined data from all 4 centres, with
      adjustment for any centre effects, using an additive model for the response
      rates. This will allow the assessment of all 6 possible pair-wise treatment
      comparisons using all available data. DISCUSSION: The strength of this trial is
      the involvement of several African countries, increasing the generalisability of
      the results. In addition, it assesses most ACTs currently available, determining
      their relative '-value-' compared to others. The balanced incomplete block design
      was chosen because using all 4-arms in each site would have increased complexity
      in terms of implementation. Excluding HIV-positive pregnant women on
      antiretroviral drugs may be seen as a limitation because of the possible
      interactions between antiretroviral and antimalarial treatments. Nevertheless,
      the results of this trial will provide the evidence base for the formulation of
      malaria treatment policy for pregnant women in sub-Saharan Africa.

PMID- 25592257
TI  - Extra money targeted at emergency services may not have been used for frontline
      care, say experts.

PMID- 25592256
TI  - Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs
      in neocortex.
AB  - Cholinergic transmission plays a pivotal role in learning, memory and cognition,
      and disturbances of cholinergic transmission have been implicated in neurological
      disorders including Alzheimer's disease, epilepsy and schizophrenia.
      Pharmacological alleviation of these diseases by drugs including N
      desmethylclozapine (NDMC), promising in animal models, often fails in patients.
      We therefore compared the effects of NDMC on glutamatergic and GABAergic
      transmission in slices from rat and human neocortex. We used carbachol (CCh; an
      established agonist at metabotropic muscarinic acetylcholine (ACh) receptors
      (mAChRs)) as a reference. Standard electrophysiological methods including
      intracellular and field potential recordings were used. In the rat neocortex,
      NDMC prevented the CCh-induced decrease of GABAA and GABAB receptor-mediated
      responses but not the CCh-induced increase of the paired-pulse depression. NDMC
      reduced neither the amplitude of the excitatory postsynaptic potentials (EPSP)
      nor antagonized the CCh-induced depression of EPSP. In the human neocortex,
      however, NDMC failed to prevent CCh-induced decrease of the GABAB responses and
      directly reduced the amplitude of EPSP. These data suggest distinct effects of
      NDMC in rat and human at M2 and M4 mAChRs underlying presynaptic modulation of
      GABA and glutamate release, respectively. In particular, NDMC might be a M2 mAChR
      antagonist in the rat but has no activity at this receptor in human neocortex.
      However, NDMC has an agonistic effect at M4 mAChR in the human but no such effect
      in the rat neocortex. The present study confirms that pharmacology at mAChRs can
      differ between species and emphasizes the need of studies in human tissue. 

PMID- 25592258
TI  - The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial
      translocation in cholestatic rats.
AB  - Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis.
      Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic
      and intestinal bile metabolism. We studied potential intestinal FXR dysfunction
      in a rat model of cholestatic liver injury and evaluated effects of obeticholic
      acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats
      were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and
      then were assessed for changes in gut permeability, BTL, and tight-junction
      protein expression, immune cell recruitment, and cytokine expression in ileum,
      mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments
      were performed with Transwell supports. Vehicle-treated bile duct-ligated rats
      exhibited decreased FXR pathway expression in both jejunum and ileum, in
      association with increased gut permeability through increased claudin-2
      expression and related to local and systemic recruitment of natural killer cells
      resulting in increased interferon-gamma expression and BTL. After INT-747
      treatment, natural killer cells and interferon-gamma expression markedly
      decreased, in association with normalized permeability selectively in ileum (up
      regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro,
      interferon-gamma induced increased Escherichia coli translocation, which remained
      unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal
      barrier function by attenuating intestinal inflammation, leading to reduced BTL
      and thus demonstrating a crucial protective role for FXR in the gut-liver axis.

PMID- 25592259
TI  - High thioredoxin reductase 1 expression in meningiomas undergoing malignant
      progression.
AB  - Thioredoxin (Trx) is a redox active protein that regulates several physiological
      and biochemical functions, such as growth, apoptosis and cellular defense. The
      function of Trx itself is regulated by thioredoxin reductase (TrxR). This study
      was designed to determine the expression of TrxR1 in meningioma tissues of
      different World Health Organization grades (grade I-III). Meningioma tissues were
      extracted from the histopathological specimens of 29 patients. These samples
      included seven histologically normal meningeal tissues that served as a control
      group and 12 grade I, 12 grade II and 5 grade III meningioma samples. TrxR1
      expression was evaluated using quantitative reverse transcription polymerase
      chain reaction (qRT-PCR) and immunostaining. The proliferative and apoptotic
      indices of the specimens were investigated by Ki-67 immunostaining and TUNEL
      assay, respectively. TrxR1 expression, as assessed by qRT-PCR, increased
      significantly with meningioma grade (p < 0.001). The immunostaining intensity of
      TrxR1 increased significantly with meningioma grade (p < 0.001). Ki-67 index
      values increased significantly in accordance with grade progression (p < 0.001).
      The apoptotic index values were not significantly different in any group (p >
      0.05). Trx system seems to be involved in the malignant progression of
      meningiomas. Further, large studies are required to elucidate the exact role of
      this system.

PMID- 25592260
TI  - Effects of a group-based reproductive management extension programme on key
      management outcomes affecting reproductive performance.
AB  - A group-based reproductive management extension programme has been designed to
      help managers of dairy herds improve herd reproductive performance. The aims of
      this study were, firstly, to assess effects of participation by key decision
      makers (KDMs) in a farmer action group programme in 2009 and 2010 on six key
      management outcomes (KMOs) that affect reproductive performance over 2 years
      (2009-2010 and 2010-2011), and secondly, to describe KDM intentions to change
      management behaviour(s) affecting each management outcome after participation in
      the programme. Seasonal calving dairy herds from four regions of New Zealand were
      enrolled in the study. Intentions to modify management behaviour were recorded
      using the formal written action plans developed during the extension programme.
      KMOs assessed were calving pattern of the herd, pre-calving heifer liveweight,
      pre-calving and premating body condition score (BCS), oestrus detection,
      anoestrus cow management and bull management. Participation was associated with
      improvements in heifer liveweight, more heifers calving in the first 6 weeks of
      the seasonal calving period, premating BCS and oestrus detection. No significant
      effects were observed on anoestrus cow management or bull management. KDMs with
      greater numbers of proposed actions had lower 6 week in-calf rates in the second
      study year than KDMs who proposed fewer actions. A more effective strategy to
      ensure more appropriate objectives is proposed. Strategies to help KDMs to
      implement proposed actions more successfully should be investigated to improve
      the programme further.

PMID- 25592262
TI  - Antimicrobial susceptibility of Histophilus somni isolated from clinically
      affected cattle in Australia.
AB  - This study investigated antimicrobial resistance traits, clonal relationships and
      epidemiology of Histophilus somni isolated from clinically affected cattle in
      Queensland and New South Wales, Australia. Isolates (n = 53) were subjected to
      antimicrobial susceptibility testing against six antimicrobial agents (ceftiofur,
      enrofloxacin, florfenicol, tetracycline, tilmicosin and tulathromycin) using disc
      diffusion and minimum inhibitory concentration (MIC) assays. Clonal relationships
      were assessed using repetitive sequence PCR and descriptive epidemiological
      analysis was performed. The H. somni isolates appeared to be geographically
      clonal, with 27/53 (47%) isolates grouping in one cluster from one Australian
      state. On the basis of disc diffusion, 34/53 (64%) isolates were susceptible to
      all antimicrobial agents tested; there was intermediate susceptibility to
      tulathromycin in 12 isolates, tilmicosin in seven isolates and resistance to
      tilmicosin in one isolate. Using MIC, all but one isolate was susceptible to all
      antimicrobial agents tested; the non-susceptible isolate was resistant to
      tetracycline, but this MIC result could not be compared to disc diffusion, since
      there are no interpretative guidelines for disc diffusion for H. somni against
      tetracycline. In this study, there was little evidence of antimicrobial
      resistance in H. somni isolates from Australian cattle. Disc diffusion
      susceptibility testing results were comparable to MIC results for most
      antimicrobial agents tested; however, results for isolates with intermediate
      susceptibility or resistance to tilmicosin and tulathromycin on disc diffusion
      should be interpreted with caution in the absence of MIC results.

PMID- 25592261
TI  - Dysregulation of tyrosine kinases and use of imatinib in small animal practice.
AB  - Imatinib inhibits the activity of several tyrosine kinases, including BCR-ABL,
      KIT and platelet-derived growth factor receptor (PDGFR). Dysregulation of KIT is
      found in mast cell tumours (MCTs) and KIT is mutated in approximately 30% and 70%
      of canine and feline MCTs, respectively. KIT mutations have also been reported in
      canine and feline gastrointestinal stromal tumours (GISTs), canine acute myeloid
      leukaemia and canine melanoma. In addition, BCR-ABL and PDGFR mutations have been
      found in canine leukaemia and haemangiosarcoma, respectively. Imatinib has anti
      tumour activity with tolerable toxicity towards a certain subset of MCTs in dogs
      and cats. Favourable clinical responses are likely to be associated with the
      presence of KIT mutation. Anti-tumour activity of imatinib has also been
      demonstrated in canine GISTs with a KIT mutation and in feline hypereosinophilic
      syndrome; however, to date only one of each of these cases has been reported. In
      conclusion, analysis of KIT mutations appears to provide valuable data for
      individual treatment with imatinib in dogs and cats.

PMID- 25592263
TI  - The conjugative DNA-transfer apparatus of Streptomyces.
AB  - Conjugation is a major route of horizontal gene transfer, an important driving
      force in the evolution of bacterial genomes. Since antibiotic producing
      streptomycetes represent a natural reservoir of antibiotic resistance genes, the
      Streptomyces conjugation system might have a particular role in the dissemination
      of the resistance genes. Streptomycetes transfer DNA in a unique process, clearly
      distinguished from the well-known DNA-transfer by type IV secretion systems. A
      single plasmid-encoded DNA-translocase, TraB, transfers a double-stranded DNA
      molecule to the recipient. Elucidation of the structure, pore forming ability and
      DNA binding characteristics of TraB indicated that the TraB conjugation system is
      derived from an FtsK-like ancestor protein suggesting that Streptomyces adapted
      the FtsK/SpoIIIE chromosome segregation system to transfer DNA between two
      distinct Streptomyces cells. Following the primary transfer, a multi-protein DNA
      translocation apparatus consisting of TraB and several Spd-proteins spreads the
      newly transferred DNA to the neighbouring mycelial compartments resulting in the
      rapid colonization of the recipient mycelium by the donor DNA. 

PMID- 25592266
TI  - Environmental risk factors associated with Helicobacter pylori seroprevalence in
      the United States: a cross-sectional analysis of NHANES data.
AB  - Helicobacter pylori imparts a considerable burden to public health. Infections
      are mainly acquired in childhood and can lead to chronic diseases, including
      gastric ulcers and cancer. The bacterium subsists in water, but the environment's
      role in transmission remains poorly understood. The nationally representative
      National Health and Nutrition Examination Survey (NHANES) was examined for
      environmental risk factors associated with H. pylori seroprevalence. Data from
      1999-2000 were examined and weighted to represent the US population.
      Multivariable logistic regression estimated adjusted odds ratios (aOR) and 95%
      confidence intervals (CI) for associations with seropositivity. Self-reported
      general health condition was inversely associated with seropositivity. Of
      participants aged <20 years, seropositivity was significantly associated with
      having a well as the source of home tap water (aOR 1.7, 95% CI 1.1-2.6) and
      living in a more crowded home (aOR 2.3, 95% CI 1.5-3.7). Of adults aged ?20
      years, seropositivity was not associated with well water or crowded living
      conditions, but adults in soil-related occupations had significantly higher odds
      of seropositivity compared to those in non-soil-related occupations (aOR 1.9, 95%
      CI 1.2-2.9). Exposures to both well water and occupationally related soil
      increased the effect size of adults' odds of seropositivity compared to non
      exposed adults (aOR 2.7, 95% CI 1.3-5.6). Environmental exposures (well-water
      usage and occupational contact with soil) play a role in H. pylori transmission.
      A disproportionate burden of infection is associated with poor health and crowded
      living conditions, but risks vary by age and race/ethnicity. These findings could
      help inform interventions to reduce the burden of infections in the United
      States. 

PMID- 25592264
TI  - Antipneumococcal activity of neuraminidase inhibiting artocarpin.
AB  - Streptococcus (S.) pneumoniae is a major cause of secondary bacterial pneumonia
      during influenza epidemics. Neuraminidase (NA) is a virulence factor of both
      pneumococci and influenza viruses. Bacterial neuraminidases (NAs) are
      structurally related to viral NA and susceptible to oseltamivir, an inhibitor
      designed to target viral NA. This prompted us to evaluate the antipneumococcal
      potential of two NA inhibiting natural compounds, the diarylheptanoid katsumadain
      A and the isoprenylated flavone artocarpin. Chemiluminescence, fluorescence-, and
      hemagglutination-based enzyme assays were applied to determine the inhibitory
      efficiency (IC(50) value) of the tested compounds towards pneumococcal NAs. The
      mechanism of inhibition was studied via enzyme kinetics with recombinant NanA NA.
      Unlike oseltamivir, which competes with the natural substrate of NA, artocarpin
      exhibits a mixed-type inhibition with a Ki value of 9.70 MUM. Remarkably,
      artocarpin was the only NA inhibitor (NAI) for which an inhibitory effect on
      pneumococcal growth (MIC: 0.99-5.75 MUM) and biofilm formation (MBIC: 1.15-2.97
      MUM) was observable. In addition, we discovered that the bactericidal effect of
      artocarpin can reduce the viability of pneumococci by a factor of >1000, without
      obvious harm to lung epithelial cells. This renders artocarpin a promising
      natural product for further investigations.

PMID- 25592265
TI  - A basis for vaccine development: Comparative characterization of Haemophilus
      influenzae outer membrane vesicles.
AB  - Outer membrane vesicles (OMVs) are spherical and bilayered particles that are
      naturally released from the outer membrane (OM) of Gram-negative bacteria. They
      have been proposed to possess several biological roles in pathogenesis and
      interbacterial interactions. Additionally, OMVs have been suggested as potential
      vaccine candidates against infections caused by pathogenic bacteria like
      Haemophilus influenzae, a human pathogen of the respiratory tract. Unfortunately,
      there is still a lack of fundamental knowledge regarding OMV biogenesis, protein
      sorting into OMVs, OMV size and quantity, as well as OMV composition in H.
      influenzae. Thus, this study comprehensively characterized and compared OMVs and
      OMs derived from heterologous encapsulated as well as nonencapsulated H.
      influenzae strains. Semiquantitative immunoblot analysis revealed that certain OM
      proteins are enriched or excluded in OMVs suggesting the presence of regulated
      protein sorting mechanisms into OMVs as well as interconnected OMV biogenesis
      mechanisms in H. influenzae. Nanoparticle tracking analysis, transmission
      electron microscopy, as well as protein and lipooligosaccharide quantifications
      demonstrated that heterologous H. influenzae strains differ in their OMV size and
      quantity. Lipidomic analyses identified palmitic acid as the most abundant fatty
      acid, while phosphatidylethanolamine was found to be the most dominant
      phospholipid present in OMVs and the OM of all strains tested. Proteomic analysis
      confirmed that H. influenzae OMVs contain vaccine candidate proteins as well as
      important virulence factors. These findings contribute to the understanding of
      OMV biogenesis as well as biological roles of OMVs and, in addition, may be
      important for the future development of OMV based vaccines against H. influenzae
      infections. 

PMID- 25592267
TI  - Early-life stress restricts the capacity of adult progenitor cells to
      differentiate into neurons.

PMID- 25592268
TI  - Glucocorticoid receptor function and resilience: a tale of mice and men.

PMID- 25592269
TI  - Posttraumatic stress disorder and autoimmune diseases.

PMID- 25592271
TI  - Inhalation of Hydrogen Gas Is Beneficial for Preventing Contrast-Induced Acute
      Kidney Injury in Rats.
AB  - Background: The present study aimed at investigating the effect of a novel
      antioxidant, hydrogen (H2) gas, on the severity of contrast-induced acute kidney
      injury (CIAKI) in a rat model. Methods: CIAKI was induced in rats by intravenous
      injection of a contrast medium, Ioversol, in addition to reagents inhibiting
      prostaglandin and nitric oxide synthesis. During the injection of these reagents,
      the rats inhaled H2 gas or control gas. Results: One day after the injection,
      serum levels of urea nitrogen were significantly lower in H2 gas-inhaling CIAKI
      rats (17.6 +/- 2.3 mg/dl) than those in control gas-treated CIAKI rats (36.0 +/-
      7.3 mg/dl), although they both were elevated as compared to untreated rats (14.9
      +/- 0.9 mg/dl). Consistently, creatinine clearance in H2 gas-treated CIAKI rats
      was higher than that in control gas-treated counterparts. Renal histological
      analysis revealed that the formation of proteinaceous casts and tubular necrosis
      was improved by H2 gas inhalation. Mechanistic analyses showed that inhalation of
      H2 gas significantly reduced renal cell apoptosis, expression of cleaved caspase
      3, and expression of an oxidative stress marker, 8-hydroxydeoxyguanosine, in
      injured kidneys. Conclusion: Results suggest that H2 gas inhalation is effective
      in ameliorating the severity of CIAKI in rats by reducing renal cell apoptosis
      and oxidative stress. (c) 2015 S. Karger AG, Basel.

PMID- 25592270
TI  - Pleiotropic roles in cancer biology for multifaceted proteins FKBPs.
AB  - BACKGROUND: FK506 binding proteins (FKBP) are multifunctional proteins highly
      conserved across the species and abundantly expressed in the cell. In addition to
      a well-established role in immunosuppression, FKBPs modulate several signal
      transduction pathways in the cell, due to their isomerase activity and the
      capability to interact with other proteins, inducing changes in conformation and
      function of protein partners. Increasing literature data support the concept that
      FKBPs control cancer related pathways. SCOPE OF THE REVIEW: The aim of the
      present article is to review current knowledge on FKBPs roles in regulation of
      key signaling pathways associated with cancer. MAJOR CONCLUSIONS: Some family
      members appear to promote disease while others are protective against
      tumorigenesis. GENERAL SIGNIFICANCE: FKBPs family proteins are expected to
      provide new biomarkers and small molecular targets, in the near future,
      increasing diagnostic and therapeutic opportunities in the cancer field. This
      article is part of a Special Issue entitled Proline-Directed Foldases: Cell
      Signaling Catalysts and Drug Targets.

PMID- 25592272
TI  - Transplantation of donor hearts after circulatory or brain death in a rat model.
AB  - BACKGROUND: Heart transplantation represents the only curative treatment for end
      stage heart failure. Presently, the donor pool is restricted to brain-dead
      donors. Based on the lack of suitable donors and the increasing number of
      patients, we investigated some molecular pathomechanisms of the potential use of
      hearts after circulatory determination of death (DCDD) in transplantation.
      MATERIALS AND METHODS: Rats were either maintained brain death for 5 h by
      inflation of a subdurally placed balloon catheter (n = 6) or subjected to cardiac
      arrest by exsanguinations (n = 6). Additionally, a control group was used (n =
      9). Then the hearts were perfused with a cold preservation solution (Custodiol),
      explanted, stored at 4 degrees C in Custodiol, and heterotopically transplanted.
      RESULTS: Brain death was associated with decreased left-ventricular contractility
      (dP/dtmax: 4895 +/- 505 versus 8037 +/- 565 mm Hg/s; ejection fraction: 27 +/- 5
      versus 44 +/- 5%; Emax: 2.2 +/- 0.3 versus 4.2 +/- 0.3 mm Hg/MUL; preload
      recruitable stroke work: 59 +/- 5 versus 96 +/- 6 mm Hg; 5 h after brain death
      versus before brain death; P < 0.05) and impaired cardiac relaxation (dP/dtmin: 
      4734 +/- 575 versus -9404 +/- 550 mm Hg/s and prolonged Tau, P < 0.05) compared
      with controls. After transplantation, significantly decreased systolic function
      and prolonged Tau were observed in brain-dead and DCDD groups compared with those
      in controls. Tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor
      kappaB, inducible-NOS, and caspase-3 messenger RNA and protein-levels were
      significantly increased in the brain-dead compared with both control and DCDD
      groups. Additionally, marked myocardial inflammatory cell infiltration, edema,
      necrosis, and DNA-strand breaks were observed in the brain-dead group.
      CONCLUSIONS: Our results show that despite the similar functional outcome in DCDD
      and brain-dead groups, brain-dead hearts showed marked myocardial inflammatory
      cell infiltration, edema, necrosis, DNA-strand breaks, and increased
      transcriptional and posttranscriptional expression for markers of apoptosis and
      inflammatory signaling pathways.

PMID- 25592273
TI  - Potential of mesenchymal stem cell in stabilization of abdominal aortic aneurysm
      sac.
AB  - BACKGROUND: In their origin, abdominal aortic aneurysms (AAAs) are related to an
      inflammatory reaction within the aortic wall, which can lead to weakness and
      degeneration of this structure. One of the most widely accepted treatment
      modalities for AAAs is the placement of stent grafts. Nevertheless, in some
      patients blood re-enters the aneurysm sac, creating so-called leaks, which
      constitute a renewed risk of rupture and death.This study explores the
      possibility of filling aneurysm sacs treated by endovascular aneurysm repair with
      adipose tissue-derived mesenchymal stem cells (ASCs) in a porcine model. METHODS:
      We developed a porcine model using 22 animals by creating an artificial AAA made
      with a Dacron patch. AAAs were then treated with a coated stent that isolated the
      aneurysm sac, after which we introduced allogeneic ASC into the sac. Animals were
      followed-up for up to 3 mo. The experiment consisted of the aforementioned
      surgical procedure performed first, followed by computed tomography and echo
      Doppler imaging during the follow-up, and finally, after sacrificing the animals,
      histologic analysis of tissue samples from the site of cell implantation by a
      blinded observer and the detection of implanted cells by immunofluorescence
      detection of the Y chromosome. RESULTS: Our findings demonstrate the survival of
      ASCs over the 3 mo after implantation and histologic changes associated with this
      treatment. Treated animals had less acute and chronic inflammation throughout the
      study period, and we observed increasing fibrosis of the aneurysm sac, no
      accumulation of calcium, and a regeneration of elastic fibers in the artery.
      CONCLUSIONS: The combination of endovascular aneurysm repair and cell therapy on
      AAAs has promising results for the stabilization of the sac, resulting in the
      generation of living tissue that can secure the stent graft and even showing some
      signs of wall regeneration. The therapeutic value of such cell-based therapy will
      require further investigation.

PMID- 25592275
TI  - Enhanced permeability, selectivity, and antifouling ability of CNTs/Al2O3
      membrane under electrochemical assistance.
AB  - Membrane filtration provides effective solutions for removing contaminants, but
      achieving high permeability, good selectivity, and antifouling ability remains a
      great challenge for existing membrane filtration technologies. In this work,
      membrane filtration coupled with electrochemistry has been developed to enhance
      the filtration performance of a CNTs/Al2O3 membrane. The as-prepared CNTs/Al2O3
      membrane, obtained by coating interconnected CNTs on an Al2O3 substrate,
      presented good pore-size tunability, mechanical stability, and
      electroconductivity. For the removal of a target (silica spheres as a probe) with
      a size comparable to the membrane pore size, the removal efficiency and flux at
      +1.5 V were 1.1 and 1.5 times higher, respectively, than those without
      electrochemical assistance. Moreover, the membrane also exhibited a greatly
      enhanced removal efficiency for contaminants smaller than the membrane pores,
      providing enhancements of 4 orders of magnitude and a factor of 5.7 for latex
      particles and phenol, respectively. These results indicated that both the
      permeability and the selectivity of CNTs/Al2O3 membranes can be significantly
      improved by electrochemical assistance, which was further confirmed by the
      removal of natural organic matter (NOM). The permeate flux and NOM removal
      efficiency at +1.5 V were about 1.6 and 3.0 times higher, respectively, than
      those without electrochemical assistance. In addition, the lost flux of the
      fouled membrane was almost completely recovered by an electrochemically assisted
      backwashing process. 

PMID- 25592274
TI  - Lymphoepithelioma-like carcinoma: a distinct type of gastric cancer.
AB  - BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare type of gastric
      carcinoma and has histologic features of intense lymphocytic infiltration. In
      this study, we attempted to analyze the clinicopathologic characteristics and
      survival outcome of patients with LELC compared with those with non
      lymphoepithelioma-like carcinoma (NLELC). METHODS: We studied 4282 patients who
      underwent gastrectomies to treat gastric cancer at the Department of Surgery of
      the Samsung Medical Center in Seoul, between January 2008 and December 2010. The
      clinicopathologic features and clinical outcomes of patients with LELC (n = 46)
      were compared with those with NLELC (n = 4236). In situ hybridization for Epstein
      Barr virus (EBV) positivity was performed on the tissue of patients with LELC (n
      = 46) and NLELC (n = 1247). RESULTS: The patients with LELC are male predominant
      and had more upper locations, more indeterminate Lauren classifications, lower T
      stages, less lymphatic invasion, and more positive EBV in situ hybridization
      compared with those of the NLELC group (80.4% versus 6.5%). Age, histologic type,
      Lauren type, the location of the tumor, the depth of the invasion, lymph node
      metastasis, and venous invasion were independent prognostic factors; however, the
      LELC type itself was not predictive of outcome. The 5-y survival rate of the LELC
      group (97.7%) was better than that of the NLELC group (89.4%); however, this
      difference was not statistically significant (P = 0.127). CONCLUSIONS: The
      results of our study suggest that LELC is a less advanced disease than NLELC in
      terms of depth of invasion and lymphatic invasion at diagnosis. However, our
      study does not examine LELC as an independent prognostic factor of gastric
      cancer. Further studies are needed to explore its associations with EBV and a
      distinct pathway of carcinogenesis from NLELC.

PMID- 25592276
TI  - TriVascular Ovation(r): it's role in solving current endograft deficiencies.
AB  - Endovascular aneurysm repair (EVAR) techniques and technologies have rapidly
      advanced over the last two decades. The basic premise of EVAR is to durably
      exclude flow from the aneurysmal sac without exerting untoward effects on the non
      diseased anatomy by using minimally invasive surgical techniques. However, these
      fundamental components have not yet been perfected with traditional stent grafts
      and remain important areas for further EVAR refinement. Latest-generation stent
      grafts are in development to accommodate these therapeutic goals. The Ovation
      Prime(r) endograft was specifically developed to address the main limitations of
      EVAR today by expanding EVAR eligibility, allowing least invasive treatment
      protocols, and protecting the proximal neck from dilatation over the long term.
      The purpose of this paper was to detail the primary deficiencies typically
      encountered with EVAR and to describe how the Ovation Prime(r) endograft
      overcomes these limitations. 

PMID- 25592277
TI  - Contemporary management of the demanding infra-renal neck in abdominal aortic
      aneurysm repair.
AB  - Proximal infrarenal neck anatomy is a crucial factor in determining outcome of
      abdominal aortic aneurysm (AAA) repair. Unfavorable or demanding infrarenal neck
      anatomy significantly increases the complexity of both standard endovascular and
      open repair resulting in increased rates of morbidity and mortality. While
      technological improvements and expanding institutional experience have resulted
      in an increased proportion of patients with an AAA with unfavorable infrarenal
      neck treated by (fenestrated) endovascular techniques, open repair has also
      remained a valid technique. The purpose of this manuscript was to describe the
      wide array of endovascular and open techniques in use to treat patients with an
      AAA with a demanding infrarenal neck and discuss their results and indications. 

PMID- 25592278
TI  - In situ fenestration: a novel option for endovascular aortic arch repair.
AB  - Aortic arch repair, is a surgical challenge irrespective of which technique is
      applied. While open surgical repair is a major trauma and a technically difficult
      procedure that many elderly patients tolerate poorly, the branched and
      fenestrated stent-grafts remain complex to implant safely. Hybrid procedures
      combine some of the advantages of both open and endovascular techniques but also
      many disadvantages. The possibility of total arch replacement with a standard off
      the-shelf thoracic stent-graft and preservation of precerebral vessels by in situ
      fenestration has recently been reported. Some technical issues remain but recent
      technical adjuncts seem to facilitate temporary cerebral shunting during
      implantation as well as piercing of the stent-graft fabric. The positioning of
      fenestrations is inherently accurate by this technique which may be associated
      with less material fatigue and improve durability. Preliminarily, this technology
      holds the promise of simpler implantation, less risk for stroke and improved
      durability of the devices. 

PMID- 25592279
TI  - Dissection of metabolic pathways in the Db/Db mouse model by integrative proteome
      and acetylome analysis.
AB  - Insulin resistance is often associated with excessive caloric intake and
      metabolic syndrome (MS) favours the development of Diabetes Mellitus Type II
      (T2DM). T2DM is a chronic disease with severe long-term consequences, such as
      dyslipidemia, retinopathy, kidney failure, and cardiovascular diseases. Although
      studied extensively, several aspects of T2DM remain poorly understood. Liver is
      the leading organ in the maintenance of metabolic fitness serving as the first
      relay station for processing dietary information in a direct response to
      nutritional input and changes in insulin and other endocrine signals. Evidence
      from several murine models suggests a unique function of the liver in the
      development of MS and T2DM. Here, we utilised Db/Db mice to understand the impact
      of T2DM on the proteome of liver cells. Global analysis of the liver proteome
      using a SILAC approach identified 407 significantly regulated proteins under
      diabetic conditions out of 8500 identified liver proteins. Furthermore, we mapped
      1604 different acetylation sites in liver proteins. After normalization of the
      protein level, we identified 34 regulated acetyl lysine residues on 21 individual
      proteins, which were significantly altered in Db/Db compared to wild-type livers.
      We reason that the dataset provides a versatile resource for functional studies
      aiming to understand consequences of changes in protein abundances and
      acetylation in livers of diabetic animals. 

PMID- 25592280
TI  - Identification and prediction of the fertile window using NaturalCycles.
AB  - OBJECTIVES: The aim of the study was to evaluate the ability of a novel web and
      mobile application to identify a woman's ovulation day and fertile window, in
      order to use it as a method of natural birth control. METHODS: A retrospective
      study was performed on 1501 cycles of 317 women aged 18 to 39 years. Women
      entered their basal body temperatures, ovulation test results and date of
      menstruation into the application. RESULTS: The mean delay from the first
      positive ovulation test to the temperature-based estimation of the ovulation day
      was 1.9 days; the length of the luteal phase varied on average by 1.25 days per
      user. Only 0.05% of non-fertile days were falsely attributed and found within the
      fertile window. CONCLUSIONS: The method is effective at identifying a user's
      ovulation day and fertile window and can therefore be used as a natural method of
      birth control.

PMID- 25592281
TI  - Clinical significance of hepatocyte growth factor/c-Met expression in the
      assessment of gastric cancer progression.
AB  - Among the mechanisms that control cancer progression, cell mobility is a
      significant factor required for cellular liberation from the primary focus and
      infiltration. Hepatocyte growth factor (HGF) has been shown to facilitate cell
      mobility. In the present study, the clinical significance of the HGF/c-Met
      pathway in the assessment of gastric cancer progression was evaluated. From a
      cohort of patients with gastric cancer who underwent surgical resection between
      April 1999 and March 2003, 110 subjects were randomly selected. Preoperative
      serum HGF levels were measured and various pathological factors were analyzed.
      Furthermore, 50 subjects were randomly selected from within this group and
      immunohistochemical staining of tissue preparations for HGF and its receptor c
      Met were performed. In the infiltrative growth pattern [(INF)alpha,beta vs.
      INFgamma], advanced progression was associated with elevated preoperative serum
      HGF levels (P<0.001). No correlation was identified between serum HGF levels and
      immunostaining for HGF or c-Met in the tissue preparations. Immunostaining
      revealed a significant correlation between c-Met expression and lymphatic vessel
      invasion (ly0.1 vs. 2.3; P=0.0416), lymph node metastasis (n0.1 vs. 2; P=0.0184)
      and maximum tumor diameter (<=50 mm vs. >50 mm; P=0.0469). Furthermore, c-Met
      positivity was associated with a significant difference in overall survival
      (P=0.0342), despite stage I and II cases accounting for 82% of the total cohort
      (41 of 50 cases). These results suggested that the expression of the HGF/c-Met
      pathway in gastric cancer may be a potential predictive factor for disease
      progression.

PMID- 25592283
TI  - Therapeutic properties of mesenchymal stem cells for autism spectrum disorders.
AB  - Recent studies of autism spectrum disorders (ASD) highlight hyperactivity of the
      immune system, irregular neuronal growth and increased size and number of
      microglia. Though the small sample size in many of these studies limits
      extrapolation to all individuals with ASD, there is mounting evidence of both
      immune and nervous system related pathogenesis in at least a subset of patients
      with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that
      no pharmacological therapy for ASD has been approved by the Food and Drug
      Administration (FDA), there is an urgent need for new therapeutic options.
      Research in the therapeutic effects of mesenchymal stem cells (MSC) for other
      immunological and neurological conditions has shown promising results in
      preclinical and even clinical studies. MSC have demonstrated the ability to
      suppress the immune system and to promote neurogenesis with a promising safety
      profile. The working hypothesis of this paper is that the potentially synergistic
      ability of MSC to modulate a hyperactive immune system and its ability to promote
      neurogenesis make it an attractive potential therapeutic option specifically for
      ASD. Theoretical mechanisms of action will be suggested, but further research is
      necessary to support these hypothetical pathways. The choice of tissue source,
      type of cell, and most appropriate ages for therapeutic intervention remain open
      questions for further consideration. Concern over poor regulatory control of stem
      cell studies or treatment, and the unique ethical challenges that each child with
      ASD presents, demands that future research be conducted with particular caution
      before widespread use of the proposed therapeutic intervention is implemented. 

PMID- 25592284
TI  - Drug release from enzyme-mediated in situ-forming hydrogel based on gum
      tragacanth-tyramine conjugate.
AB  - In the present study, injectable hydrogels based on gum tragacanth-tyramine
      conjugate were prepared by enzymatic oxidation of tyramine radicals in the
      presence of hydrogen peroxide. Then, in vitro release of bovine serum albumin and
      insulin as model protein drugs from this polymeric network was investigated.
      Also, to improve the properties of this hydrogel, a blended hydrogel composed of
      tyramine-conjugated gelatin and tyramine-conjugated tragacanth was prepared.
      Experimental results showed that the gelation time ranged from 3 to 28 s
      depending on the polymer and enzyme concentrations. Results of morphological
      investigation of hydrogels indicated that the average pore size of hydrogels
      varied from 120 to 160 um. Swelling degree of hydrogels and the rate of drug
      release decreased by increasing of hydrogen peroxide and polymer concentrations.
      The release profile of drug from hydrogels followed Higuchi and Fickian diffusion
      mechanism. Finally, it was shown that the swelling characteristics and drug
      release behavior of this polymeric network could be improved by blending it with
      tyramine-conjugated gelatin.

PMID- 25592285
TI  - Poly-3-hydroxybutyrate-co-3-hydroxyvalerate containing scaffolds and their
      integration with osteoblasts as a model for bone tissue engineering.
AB  - Nano/micro engineered polymeric materials offer expansive scope of biomimetic
      scaffolds for bone tissue engineering especially those involving electrospun
      biodegradable nanofibers incorporated with inorganic nanoparticles, thus
      mimicking the extracellular matrix of bone both structurally and chemically. For
      the first time, poly-3-hydroxybutyrate-co-3-hydroxyvalerate containing natural
      poly-(alpha, beta)-DL-aspartic acid and inorganic hydroxyapatite nanofibers were
      fabricated using poly-3-hydroxybutyrate-co-3-hydroxyvalerate: poly-(alpha, beta)
      DL-aspartic acid at a ratio of 80:20 (w/w) added with 1% (w/v) of hydroxyapatite,
      by the process of electrospinning. The surface morphology, chemical, and
      mechanical properties of electrospun poly-3-hydroxybutyrate-co-3-hydroxyvalerate,
      poly-3-hydroxybutyrate-co-3-hydroxyvalerate/poly-(alpha, beta)-DL-aspartic acid,
      and poly-3-hydroxybutyrate-co-3-hydroxyvalerate/poly-(alpha, beta)-DL-aspartic
      acid/hydroxyapatite nanofibers were characterized by using field emission
      scanning electron microscope, Fourier transform infrared spectroscopy, and
      tensile tester, respectively. Human fetal osteoblasts were cultured on different
      nanofibrous scaffolds for evaluating the cell proliferation, alkaline phosphatase
      activity, and mineralization. Cells on poly-3-hydroxybutyrate-co-3
      hydroxyvalerate/poly-(alpha, beta)-DL-aspartic acid/hydroxyapatite scaffolds
      demonstrated higher proliferation (30.10%) and mineral deposition (37.60%) than
      the cells grown on pure poly-3-hydroxybutyrate-co-3-hydroxyvalerate scaffolds.
      Obtained results highlight the synergistic effect of poly-3-hydroxybutyrate-co-3
      hydroxyvalerate, poly-(alpha, beta)-DL-aspartic acid, and hydroxyapatite towards
      the enhancement of the osteoinductivity and osteoconductivity of human fetal
      osteoblasts, demonstrating the appropriate physicochemical and biological
      properties of poly-3-hydroxybutyrate-co-3-hydroxyvalerate/poly-(alpha, beta)-DL
      aspartic acid/hydroxyapatite nanofibers to function as a substrate for bone
      tissue regeneration.

PMID- 25592282
TI  - Mesenchymal stem cells detect and defend against gammaherpesvirus infection via
      the cGAS-STING pathway.
AB  - Mesenchymal stem cells (MSCs) are widely used in clinical settings to treat
      tissue injuries and autoimmune disorders due to their multipotentiality and
      immunomodulation. Long-term observations reveal several complications after MSCs
      infusion, especially herpesviral infection. However, the mechanism of host
      defense against herpesviruses in MSCs remains largely unknown. Here we showed
      that murine gammaherpesvirus-68 (MHV-68), which is genetically and biologically
      related to human gammaherpesviruses, efficiently infected MSCs both in vitro and
      in vivo. Cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) was identified as
      the sensor of MHV-68 in MSCs for the first time. Moreover, the cytosolic DNA
      sensing pathway mediated a potent anti-herpesviral effect through the adaptor
      STING and downstream kinase TBK1. Furthermore, blockade of IFN signaling
      suggested that cytosolic DNA sensing triggered both IFN-dependent and 
      independent anti-herpesviral responses. Our findings demonstrate that cGAS-STING
      mediates innate immunity to gammaherpesvirus infection in MSCs, which may provide
      a clue to develop therapeutic strategy. 

PMID- 25592286
TI  - Exercise at depth alters bradycardia and incidence of cardiac anomalies in deep
      diving marine mammals.
AB  - Unlike their terrestrial ancestors, marine mammals routinely confront extreme
      physiological and physical challenges while breath-holding and pursuing prey at
      depth. To determine how cetaceans and pinnipeds accomplish deep-sea chases, we
      deployed animal-borne instruments that recorded high-resolution
      electrocardiograms, behaviour and flipper accelerations of bottlenose dolphins
      (Tursiops truncatus) and Weddell seals (Leptonychotes weddellii) diving from the
      surface to >200 m. Here we report that both exercise and depth alter the
      bradycardia associated with the dive response, with the greatest impacts at
      depths inducing lung collapse. Unexpectedly, cardiac arrhythmias occurred in >73%
      of deep, aerobic dives, which we attribute to the interplay between sympathetic
      and parasympathetic drivers for exercise and diving, respectively. Such marked
      cardiac variability alters the common view of a stereotypic 'dive reflex' in
      diving mammals. It also suggests the persistence of ancestral terrestrial traits
      in cardiac function that may help explain the unique sensitivity of some deep
      diving marine mammals to anthropogenic disturbances. 

PMID- 25592287
TI  - Ethics rounds do not improve the handling of ethical issues by psychiatric staff.
AB  - BACKGROUND: One way to support healthcare staff in handling ethically difficult
      situations is through ethics rounds that consist of discussions based on clinical
      cases and are moderated by an ethicist. Previous research indicates that the
      handling of ethically difficult situations in the workplace might have changed
      after ethics rounds. This, in turn, would mean that the "ethical climate", i.e.
      perceptions of how ethical issues are handled, would have changed. AIM: To
      investigate whether ethics rounds could improve the ethical climate perceived by
      staff working in psychiatry outpatient clinics. METHODS: In this quasi
      experimental study, six inter-professional ethics rounds led by a
      philosopher/ethicist were conducted at two psychiatry outpatient clinics. Changes
      in ethical climate were measured at these clinics as well as at two control
      clinics at baseline and after the intervention period using the instrument
      Hospital Ethical Climate Survey. RESULTS: Within-groups comparisons of median sum
      scores of ethical climate showed that no statistically significant differences
      were found in the intervention group before or after the intervention period. The
      median sum scores for ethical climate were significantly higher, both at baseline
      and after the intervention period (P <= 0.001; P = 0.046), in the intervention
      group. CONCLUSIONS: Ethics rounds in psychiatric outpatient clinics did not
      result in significant changes in ethical climate. Outcomes of ethics rounds
      might, to a higher degree, be directed towards patient-related outcomes rather
      than towards the staff's working environment, as the questions brought up for
      discussion during the ethics rounds concerned patient-related issues.

PMID- 25592288
TI  - Superficiality in forensic psychiatric patients is related to superior
      phonological, semantic and syntactic skills.
AB  - BACKGROUND: Psychopaths are reported to have unusual language processing, and
      they have been suggested to have better phonological awareness than do non
      psychopaths. Phonological processing skills have not been studied among
      psychopathic persons, and it is unclear how the degree of psychopathy is related
      to such skills. AIMS: One aim of the present study was to investigate this
      relationship. An additional aim was to investigate how affective-interpersonal
      traits and antisocial lifestyle of psychopaths are related to verbal skills such
      as reading and spelling, as well as to phonological processing skills. MATERIAL
      AND METHODS: Forty (80% male) forensic psychiatric patients participated. They
      were all Swedish speaking and their mean age was 36 years. The patients performed
      reading and spelling tests as well as a battery of tasks assessing phonological
      processing. The patients were also assessed using the Psychopathy Checklist:
      Screening Version (PCL:SV). RESULTS: The patients' scores on Factor 1 (affective
      and interpersonal traits) of the PCL:SV were significantly positively correlated
      with results on decoding of sentences and reading speed tests as well as with
      phonological processing skills. However, the only item that was significantly
      related to phonological processing skills as well as semantic and syntactic
      skills was Superficial. CONCLUSIONS: In general, psychopaths easily shift
      conversational topics, and it may be due to a certain cognitive skill such as
      rapid automatized naming. We suggest that further studies focus on rapid
      automatized naming in psychopaths to clarify whether their superficial character
      might be related to rapid naming.

PMID- 25592289
TI  - Neuroendocrine tumours of the female genital tract: a case-based imaging review
      with pathological correlation.
AB  - BACKGROUND: Both primary and secondary gynaecological neuroendocrine (NE) tumours
      are uncommon, and the literature is scarce concerning their imaging features.
      METHODS: This article reviews the epidemiological, clinical and imaging features
      with pathological correlation of gynaecological NE tumours. RESULTS: The clinical
      features of gynaecological NE tumours are non-specific and depend on the organ of
      origin and on the extension and aggressiveness of the disease. The imaging
      approach to these tumours is similar to that for other histological types and the
      Revised International Federation of Gynecology and Obstetrics (FIGO) Staging
      System also applies to NE tumours. Neuroendocrine tumours were recently divided
      into two groups: poorly differentiated neuroendocrine carcinomas (NECs) and well
      differentiated neuroendocrine tumours (NETs). NECs include small cell carcinoma
      and large cell neuroendocrine carcinoma, while NETs account for typical and
      atypical carcinoids. Cervical small cell carcinoma and ovarian carcinoid are the
      most common gynaecological NE tumours. The former typically behaves aggressively;
      the latter usually behaves in a benign fashion and tends to be confined to the
      organ. CONCLUSION: While dealing with ovarian carcinoids, extra-ovarian
      extension, bilaterality and multinodularity raise the suspicion of metastatic
      disease. NE tumours of the endometrium and other gynaecological locations are
      very rare. TEACHING POINTS: * Primary or secondary neurondocrine (NE) tumours of
      the female genital tract are rare. * Cervical small cell carcinoma and ovarian
      carcinoids are the most common gynaecological NE tumours. * Cervical small cell
      carcinomas usually behave aggressively. * Ovarian carcinoids tend to behave in a
      benign fashion. * The imaging approach to gynaecological NE tumours and other
      histological types is similar.

PMID- 25592290
TI  - A computerized framework for monitoring four-dimensional dose distributions
      during stereotactic body radiation therapy using a portal dose image-based 2D/3D
      registration approach.
AB  - A computerized framework for monitoring four-dimensional (4D) dose distributions
      during stereotactic body radiation therapy based on a portal dose image (PDI)
      based 2D/3D registration approach has been proposed in this study. Using the PDI
      based registration approach, simulated 4D "treatment" CT images were derived from
      the deformation of 3D planning CT images so that a 2D planning PDI could be
      similar to a 2D dynamic clinical PDI at a breathing phase. The planning PDI was
      calculated by applying a dose calculation algorithm (a pencil beam convolution
      algorithm) to the geometry of the planning CT image and a virtual water
      equivalent phantom. The dynamic clinical PDIs were estimated from electronic
      portal imaging device (EPID) dynamic images including breathing phase data
      obtained during a treatment. The parameters of the affine transformation matrix
      were optimized based on an objective function and a gamma pass rate using a
      Levenberg-Marquardt (LM) algorithm. The proposed framework was applied to the
      EPID dynamic images of ten lung cancer patients, which included 183 frames (mean:
      18.3 per patient). The 4D dose distributions during the treatment time were
      successfully obtained by applying the dose calculation algorithm to the simulated
      4D "treatment" CT images. The mean+/-standard deviation (SD) of the percentage
      errors between the prescribed dose and the estimated dose at an isocenter for all
      cases was 3.25+/-4.43%. The maximum error for the ten cases was 14.67%
      (prescribed dose: 1.50Gy, estimated dose: 1.72Gy), and the minimum error was
      0.00%. The proposed framework could be feasible for monitoring the 4D dose
      distribution and dose errors within a patient's body during treatment. 

PMID- 25592292
TI  - Sink or swim: using density as a signal for quantitative immunoassays.

PMID- 25592293
TI  - The incidence of thyroid cartilage invasion through the anterior commissure in
      clinically early-staged laryngeal cancer.
AB  - In this study, the incidence of thyroid cartilage invasion in early-stage
      laryngeal tumors involving anterior commissure was assessed. Medical charts and
      pathology reports of 62 patients who underwent supracricoid partial laryngectomy
      as the primary treatment of early-staged laryngeal squamous cell carcinoma were
      retrospectively reviewed. Patients were divided into two groups according to the
      macroscopic examination of the surgical specimen: tumors limited to the glottis
      with the involvement of anterior commissure (TLG); tumors invading both
      supraglottis and glottis with the involvement of anterior commissure (TISG).
      Thirty-seven of the cases were classified as TLG group (59.7 %) and the remaining
      25 of them were classified as TISG group (40.3 %). Thyroid cartilage invasion was
      observed totally in ten patients (16.1 %), as macroscopic invasion in two cases
      and microinvasion in eight patients. Only two were in the TLG group (cartilage
      invasion rate of 5.4 %), the remaining eight were in the TISG group (cartilage
      invasion rate of 32 %). Thyroid cartilage invasion rate of TISG group was
      significantly higher than that of TLG group (p = 0.011, p < 0.05). Tumors limited
      to the glottis with AC involvement may be more suitable for endoscopic resection;
      on the contrary, tumors with vertical extension invading both AC and supraglottis
      should be evaluated more suspiciously due to high rate of thyroid cartilage
      invasion, which may still necessitate external laryngectomy techniques.

PMID- 25592291
TI  - Loss of periostin/OSF-2 in ErbB2/Neu-driven tumors results in androgen receptor
      positive molecular apocrine-like tumors with reduced Notch1 activity.
AB  - INTRODUCTION: Periostin (Postn) is a secreted cell adhesion protein that
      activates signaling pathways to promote cancer cell survival, angiogenesis,
      invasion, and metastasis. Interestingly, Postn is frequently overexpressed in
      numerous human cancers, including breast, lung, colon, pancreatic, and ovarian
      cancer. METHODS: Using transgenic mice expressing the Neu oncogene in the mammary
      epithelium crossed into Postn-deficient animals, we have assessed the effect of
      Postn gene deletion on Neu-driven mammary tumorigenesis. RESULTS: Although Postn
      is exclusively expressed in the stromal fibroblasts of the mammary gland, Postn
      deletion does not affect mammary gland outgrowth during development or pregnancy.
      Furthermore, we find that loss of Postn in the mammary epithelium does not alter
      breast tumor initiation or growth in mouse mammary tumor virus (MMTV)-Neu
      expressing mice but results in an apocrine-like tumor phenotype. Surprisingly, we
      find that tumors derived from Postn-null animals express low levels of Notch
      protein and Hey1 mRNA but increased expression of androgen receptor (AR) and AR
      target genes. We show that tumor cells derived from wild-type animals do not
      proliferate when transplanted in a Postn-null environment but that this growth
      defect is rescued by the overexpression of active Notch or the AR target gene
      prolactin-induced protein (PIP/GCDFP-15). CONCLUSIONS: Together our data suggest
      that loss of Postn in an ErbB2/Neu/HER2 overexpression model results in apocrine
      like tumors that activate an AR-dependent pathway. This may have important
      implications for the treatment of breast cancers involving the therapeutic
      targeting of periostin or Notch signaling.

PMID- 25592294
TI  - Schizophrenia in the spectrum of gene-stress interactions: the FKBP5 example.
AB  - Many studies have demonstrated that genotype (G) interacts with adverse life
      experiences (E) to produce individual differences in vulnerability and resilience
      to mental disorders, including schizophrenia. Genetic susceptibility to stress
      and the timing of the environmental exposure(s) are relevant for these
      interactions and represent common risk factors. We take the example of the FKBP5
      gene to illustrate G * E interactions that predict pleiotropic psychiatric
      outcomes, including schizophrenia. 

PMID- 25592295
TI  - Using a framework to implement large-scale innovation in medical education with
      the intent of achieving sustainability.
AB  - BACKGROUND: Particularly when undertaken on a large scale, implementing
      innovation in higher education poses many challenges. Sustaining the innovation
      requires early adoption of a coherent implementation strategy. Using an example
      from clinical education, this article describes a process used to implement a
      large-scale innovation with the intent of achieving sustainability. Desire to
      improve the effectiveness of undergraduate medical education has led to growing
      support for a longitudinal integrated clerkship (LIC) model. This involves a move
      away from the traditional clerkship of 'block rotations' with frequent changes in
      disciplines, to a focus upon clerkships with longer duration and opportunity for
      students to build sustained relationships with supervisors, mentors, colleagues
      and patients. A growing number of medical schools have adopted the LIC model for
      a small percentage of their students. At a time when increasing medical school
      numbers and class sizes are leading to competition for clinical supervisors it is
      however a daunting challenge to provide a longitudinal clerkship for an entire
      medical school class. This challenge is presented to illustrate the strategy used
      to implement sustainable large scale innovation. WHAT WAS DONE: A strategy to
      implement and build a sustainable longitudinal integrated community-based
      clerkship experience for all students was derived from a framework arising from
      Roberto and Levesque's research in business. The framework's four core processes:
      chartering, learning, mobilising and realigning, provided guidance in preparing
      and rolling out the 'whole of class' innovation. DISCUSSION: Roberto and
      Levesque's framework proved useful for identifying the foundations of the
      implementation strategy, with special emphasis on the relationship building
      required to implement such an ambitious initiative. Although this was innovation
      in a new School it required change within the school, wider university and health
      community. Challenges encountered included some resistance to moving away from
      traditional hospital-centred education, initial student concern, resource
      limitations, workforce shortage and potential burnout of the innovators. Large
      scale innovations in medical education may productively draw upon research from
      other disciplines for guidance on how to lay the foundations for successfully
      achieving sustainability.

PMID- 25592297
TI  - Morning serum Basal cortisol levels are affected by age and pubertal maturation
      in school-aged children and adolescents.
AB  - BACKGROUND: The same reference values for cortisol have been used for adults and
      children, but laboratory results obtained from an adult population might not be
      suitable for pediatric patients. AIMS: To determine morning serum basal cortisol
      levels in children and adolescents. METHODS: The study was conducted on 120
      suitable reference individuals, healthy Brazilian children and adolescents from
      both genders aged 4-19 years old. The method used for cortisol assessment was the
      chemiluminescent enzyme immunoassay (VITROS(r) 5600 MicroWell; Johnson & Johnson,
      High Wycombe, UK, 2009), and the kit reference interval was 4.46-22.7 MUg/dl
      (122.7-626.2 nmol/l). The setting limits were calculated according to the
      Clinical Laboratory Standards Institute guidelines. RESULTS: The morning serum
      basal cortisol levels increased with age and pubertal maturation, but there were
      no differences based on gender. The cortisol reference values were established
      based on the 2.5th and 97.5th percentiles as 2.97 MUg/dl [81.9 nmol/l, 90%
      confidence interval (CI) 1.44-3.69 MUg/dl] and 23.4 MUg/dl (645.5 nmol/l; 90% CI
      16.3-26.4 MUg/dl), respectively. CONCLUSIONS: The assessment of the morning serum
      basal cortisol levels showed a unique pattern, with a different lower limit for
      the cohort compared to current values established for adult subjects.

PMID- 25592296
TI  - Integrin alpha L controls the homing of regulatory T cells during CNS
      autoimmunity in the absence of integrin alpha 4.
AB  - Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple
      sclerosis (MS), results from an autoimmune attack of the central nervous system
      (CNS) by effector T helper (Th) 1 and Th17 cells. Regulatory T cells (Treg) can
      control effector T cells and limit the progression of CNS autoimmunity. Integrin
      alpha 4 (Itga4) is critical for the entry of Th1 but not Th17 cells into the CNS
      during EAE. Whether Itga4 controls the homing of Tregs in the CNS and whether
      Tregs can limit Th17-mediated EAE has, however, not been addressed. Through
      selective elimination of Itga4 in Foxp3-expressing cells, we show here that Tregs
      can suppress Th17-mediated EAE and enter into the CNS independently of Itga4.
      Furthermore, similarly to Th17 cells and in contrast to Th1 cells, Tregs depend
      on LFA-1 for their entry into the CNS in the absence of Itga4. Therefore, these
      data suggest that the efficacy of Itga4 neutralization on MS progression may be
      associated with the prevention of Th1 cells and the maintenance of Tregs
      migration into the CNS. 

PMID- 25592298
TI  - Coronary artery disease in lung transplant candidates: role of routine invasive
      assessment.
AB  - BACKGROUND: An atherosclerotic disease burden sufficient to put lung transplant
      candidates at risk for end-organ disease after transplantation is considered to
      be a relative contraindication for lung transplantation. OBJECTIVES: The aim of
      this study was to assess our current practice of cardiac workup by coronary
      angiography in lung transplant candidates >=50 years of age. METHODS: We
      retrospectively analyzed 50 consecutive lung transplant candidates >=50 years of
      age in which coronary angiography was performed at the University Hospital Zurich
      (2009-2013). For every patient, the risk of developing an acute coronary event
      was estimated by using a recalibrated version of the PROCAM study calculator for
      the Swiss population. RESULTS: The median estimated risk of developing an acute
      coronary event within 10 years in the study cohort (n = 50) was 4.2%
      (interquartile range 1.9-7.6), which is considered to be a low risk. Sixteen
      percent of patients were considered to be at intermediate risk. In 66% of
      patients, coronary angiography showed no coronary artery disease (CAD). In 28% of
      patients, CAD without significant stenosis was diagnosed. In 6% of patients,
      significant coronary stenosis was detected requiring percutaneous coronary
      intervention. No correlation between the coronary status and the risk score or
      cardiovascular risk profile was found. CONCLUSIONS: The high prevalence of
      asymptomatic CAD in lung transplant candidates without correlation to a common
      clinical risk score supports the important role of coronary angiography for the
      assessment of coronary artery status. This approach might prevent cardiovascular
      events and improve long-term survival after transplantation.

PMID- 25592299
TI  - Haloperidol versus first-generation antipsychotics for the treatment of
      schizophrenia and other psychotic disorders.
AB  - BACKGROUND: Haloperidol is worldwide one of the most frequently used
      antipsychotic drugs with a very high market share. Previous narrative,
      unsystematic reviews found no differences in terms of efficacy between the
      various first-generation ("conventional", "typical") antipsychotic agents. This
      established the unproven psychopharmacological assumption of a comparable
      efficacy between the first-generation antipsychotic compounds codified in
      textbooks and treatment guidelines. Because this assumption contrasts with the
      clinical impression, a high-quality systematic review appeared highly necessary.
      OBJECTIVES: To compare the efficacy, acceptability, and tolerability of
      haloperidol with other first-generation antipsychotics in schizophrenia and
      schizophrenia-like psychosis. SEARCH METHODS: In October 2011 and July 2012, we
      searched the Cochrane Schizophrenia Group's Trials Register, which is based on
      regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and
      registries of clinical trials. To identify further relevant publications, we
      screened the references of all included studies and contacted the manufacturers
      of haloperidol for further relevant trials and missing information on identified
      studies. Furthermore, we contacted the corresponding authors of all included
      trials for missing data. SELECTION CRITERIA: We included all randomised
      controlled trials (RCTs) that compared oral haloperidol with another oral first
      generation antipsychotic drug (with the exception of the low-potency
      antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine,
      perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia
      like psychosis. Clinically important response to treatment was defined as the
      primary outcome. Secondary outcomes were global state, mental state, behaviour,
      overall acceptability (measured by the number of participants leaving the study
      early due to any reason), overall efficacy (attrition due to inefficacy of
      treatment), overall tolerability (attrition due to adverse events), and specific
      adverse effects. DATA COLLECTION AND ANALYSIS: At least two review authors
      independently extracted data from the included trials. The methodological quality
      of the included studies was assessed using The Cochrane Collaboration's 'Risk of
      bias' tool.We analysed dichotomous outcomes with risk ratios (RR) and continuous
      outcomes with mean differences (MD), both with the associated 95% confidence
      intervals (CI). All analyses were based on a random-effects model and we
      preferably used data on an intention-to-treat basis where possible. MAIN RESULTS:
      The systematic review currently includes 63 randomised trials with 3675
      participants. Bromperidol (n = 9), loxapine (n = 7), and trifluoperazine (n = 6)
      were the most frequently administered antipsychotics comparator to haloperidol.
      The included studies were published between 1962 and 1993, were characterised by
      small sample sizes (mean: 58 participants, range from 18 to 206) and the
      predefined outcomes were often incompletely reported. All results for the main
      outcomes were based on very low or low quality data. In many trials the mechanism
      of randomisation, allocation, and blinding was frequently not reported. In short
      term studies (up to 12 weeks), there was no clear evidence of a difference
      between haloperidol and the pooled group of the other first-generation
      antipsychotic agents in terms of the primary outcome "clinically important
      response to treatment" (40 RCTs, n = 2132, RR 0.93 CI 0.87 to 1.00). In the
      medium-term trials, haloperidol may be less effective than the other first
      generation antipsychotic group but this evidence is based on only one trial (1
      RCT, n = 80, RR 0.51 CI 0.37 to 0.69).Based on limited evidence, haloperidol
      alleviated more positive symptoms of schizophrenia than the other antipsychotic
      drugs. There were no statistically significant between-group differences in
      global state, other mental state outcomes, behaviour, leaving the study early due
      to any reason, due to inefficacy, as well as due to adverse effects. The only
      statistically significant difference in specific side effects was that
      haloperidol produced less akathisia in the medium term. AUTHORS' CONCLUSIONS: The
      findings of the meta-analytic calculations support the statements of previous
      narrative, unsystematic reviews suggesting comparable efficacy of first
      generation antipsychotics. In efficacy-related outcomes, there was no clear
      evidence of a difference between the prototypal drug haloperidol and other,
      mainly high-potency first-generation antipsychotics. Additionally, we
      demonstrated that haloperidol is characterised by a similar risk profile compared
      to the other first-generation antipsychotic compounds. The only statistically
      significant difference in specific side effects was that haloperidol produced
      less akathisia in the medium term. The results were limited by the low
      methodological quality in many of the included original studies. Data for the
      main results were low or very low quality. Therefore, future clinical trials with
      high methodological quality are required.

PMID- 25592300
TI  - Partial nephrectomy for the treatment of translocation renal cell carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the outcome of patients with
      translocation renal cell carcinoma (RCC) treated with partial nephrectomy.
      PATIENTS AND METHODS: Our institutional review board-approved renal mass registry
      was queried for patients who underwent partial nephrectomy for a pathologically
      confirmed translocation RCC. We describe the demographic, clinical, pathological,
      and follow-up data for this series of patients. RESULTS: Between 2003 and 2013,
      1897 patients with RCC were treated at our institution with a radical or partial
      nephrectomy. In total, 10 (0.5%) patients were diagnosed with a translocation
      RCC. Of these patients, 4 (40%) underwent treatment with partial nephrectomy for
      an incidentally detected small renal mass (mean imaging diameter, 2.6 cm [range,
      1.0-4.2 cm]). During a mean follow-up of 37 months (range, 8-81 months), all
      patients were alive without evidence of disease. CONCLUSION: At short-term follow
      up, partial nephrectomy appears to be an effective treatment option for patients
      with small translocation RCCs. Larger studies are required to more extensively
      investigate the optimal treatment of these potentially aggressive tumors.

PMID- 25592301
TI  - A qualitative study on how Muslim women of Moroccan descent approach antenatal
      anomaly screening.
AB  - OBJECTIVE: to extend the knowledge on Muslim women's approach of antenatal
      anomaly screening. DESIGN: qualitative interview study with pregnant Muslim women
      from Moroccan origin. SETTING: one midwifery practice in a medium-sized city near
      Amsterdam participated in the study. PARTICIPANTS: twelve pregnant Muslim women
      who live in a high density immigrant area and who attended primary midwives for
      antenatal care were included in the study. DATA COLLECTION AND DATA ANALYSES: we
      conducted open interviews with pregnant Moroccan Muslim women for the purpose of
      studying how they made decisions about antenatal anomaly screening. We used a
      thematic analysis approach. FINDINGS: women experienced the combined test as 'a
      test' that could identify potentially anomalous infants, and could result in
      being offered termination of the pregnancy; a fact that resulted in their
      extensive deliberations and hesitation about the test uptake. Only two women had
      the combined test. Conversely, women opted for the Fetal Anomaly Scan and saw it
      as 'only an ultrasound to see the baby'. Above all, women emphasised that whether
      or not to participate in antenatal anomaly tests was their own, individual
      decision as ultimately they were accountable for their choices. All women,
      including nulliparous women, viewed becoming pregnant as the point of becoming a
      mother - and considered antenatal screening through the lens of motherhood. KEY
      CONCLUSIONS: motherhood was the lens through which the decision to participate in
      antenatal anomaly screening was approached. Religious beliefs influenced values
      on termination and disability and were influential in the deliberations for
      antenatal testing. Combined test but not Fetal Anomaly Scan was considered to be
      a antenatal screening test. IMPLICATIONS FOR PRACTICE: counsellors should have
      knowledge of the different Islamic beliefs about - the latest possible day for -
      termination and an awareness that Muslim women make their own conscious choices,
      also beyond Islamic rulings.

PMID- 25592303
TI  - Current trends in antibiotic prophylaxis for laryngectomy in the UK - a national
      survey.
AB  - BACKGROUND: With the increasing use of chemoradiotherapy protocols, total
      laryngectomy carries increasing risks such as pharyngocutaneous fistula. There is
      little reference to the use of antibiotic prophylaxis in salvage surgery. This
      study aimed to determine the current practice in antibiotic prophylaxis for total
      laryngectomy in the UK. METHOD: A questionnaire was designed using SurveyMonkey
      software, and distributed to all ENT-UK registered head and neck surgeons.
      RESULTS: The survey revealed that 19 surgeons (51 per cent) follow a protocol for
      antibiotic prophylaxis in primary total laryngectomy and 17 (46 per cent) follow
      a protocol in salvage total laryngectomy. Only 11 (30 per cent) use anti
      methicillin-resistant Staphylococcus aureus agents in their antibiotic
      prophylaxis. The duration of prophylaxis varies considerably. Nineteen surgeons
      (51 per cent) revealed that their choice of antibiotic prophylaxis reflected non
      evidence-based practices. CONCLUSION: There appears to be little evidence-based
      guidance on antibiotic prophylaxis in primary and salvage total laryngectomy. The
      survey highlights the need for more research in order to inform national guidance
      on antibiotic prophylaxis in primary and salvage total laryngectomy.

PMID- 25592304
TI  - Silencing NOB1 enhances doxorubicin antitumor activity of the papillary thyroid
      carcinoma in vitro and in vivo.
AB  - Doxorubicin (DOX), a broad-spectrum anthra-cyclin, is in wide clinical use for
      the treatment and prevention of thyroid cancer. However, the effectiveness of the
      treatment remains limited due to inherent tumor resistance to DOX. Results of a
      previous study demonstrated that downregulation of NIN1/RPN12 binding protein 1
      homolog (NOB1) expression via adenovirus expression vector carrying NOB1 siRNA
      (Ad/sh-NOB1) induced cancer apoptosis and increased the radiosensitivity of
      papillary thyroid carcinoma (PTC) cells. However, whether knockout NOB1 can
      decrease DOX resistance remains unclear. Therefore, in the present study, the
      effect of Ad/sh-NOB1 infection, independently or in combination with DOX, was
      determined in a PTC cell line to identify more effective therapeutics against PTC
      cancer. Furthermore, tumor growth ability in nude mice was determined to identify
      the combination treatment effect in tumorigenesis in vivo. The results showed
      that Ad/sh-NOB1 combined with DOX treatment in PTC cells significantly suppressed
      proliferation, colony formation, migration and invasion, and induced cell
      apoptosis and arrest in the G0/G1 stage as compared to Ad/sh-NOB1 or DOX
      monotherapy. We also found that this combination suppressed the tumor growth of a
      nude mouse model as compared to Ad/sh-NOB1 or DOX monotherapy. In addition, Ad/sh
      NOB1 combined with DOX treatment significantly increased activation of the p38
      MAPK pathway, which may contribute to inhibition of PTC cell growth and decreased
      DOX resistance. Taken together, the experimental results indicate that Ad/sh-NOB1
      combined with DOX treatment is a potential drug candidate for the treatment of
      papillary thyroid carcinoma.

PMID- 25592305
TI  - A critical review of "Internet addiction" criteria with suggestions for the
      future.
AB  - AIMS: In the last 5 years a deluge of articles on the topic of Internet addiction
      (IA) has proposed many candidate symptoms as evidence of this proposed disease.
      We critically reviewed the current approach to the measurement and identification
      of this new excessive behavior syndrome. METHODS: Three popular models of IA were
      discussed: Griffith's components model; Young's Internet Addiction Test (IAT);
      and the criteria by Tao et al. (2010). We selected these models because they are
      widely cited and propose specific criteria for IA disorder. Our approach is not
      meant to provide an exhaustive review, but to discuss and critique the most
      salient trends in the field. RESULTS: The models of Internet addiction share some
      criteria, including feeling a loss of control over Internet use; ensuing
      psychological, social, or professional conflict or problems; and preoccupation
      when not using the Internet. Other criteria inconsistently mentioned include:
      mood management, tolerance, withdrawal, and craving/anticipation. The models
      studied here share the assumption that the Internet can produce a qualitative
      shift to a diseased state in humans. CONCLUSIONS: We critically discussed the
      above criteria and concluded that the evidence base is currently not strong
      enough to provide support for an Internet addiction disorder. Future research
      areas are suggested: (1) Focusing on common impaired dimensions, (2) exploring
      neuroimaging as a model building tool, and (3) identifying shifts in the
      rewarding aspects of Internet use. Given the lack of consensus on the subject of
      Internet addiction, a focus on problem behaviors appears warranted.

PMID- 25592306
TI  - Compulsive sexual behavior among male military veterans: prevalence and
      associated clinical factors.
AB  - BACKGROUND AND AIMS: Compulsive sexual behavior (CSB) is highly prevalent among
      men, often co-occurring with psychiatric disorders and traumatic experiences.
      Psychiatric disorders and trauma are highly prevalent among military veterans,
      yet there is a paucity of research on CSB among military samples. The aim of this
      study was to examine the prevalence of and factors associated with CSB among male
      military veterans. METHODS: Surveys were administered to veterans of Operations
      Iraqi Freedom, Enduring Freedom, or New Dawn at baseline (n = 258), 3 months(n =
      194), and 6 months (n = 136). Bivariate analyses and Generalized Estimating
      Equations were utilized to estimate associations between CSB and the following
      variables: psychiatric co-morbidity, childhood physical or sexual trauma, pre-
      and post-deployment experiences, TV/ Internet usage, and sociodemographics.
      Associations between CSB and specific PTSD symptom clusters were also examined.
      RESULTS: CSB was reported by 16.7% of the sample at baseline. Several variables
      were associated with CSB in bivariate analyses; however, only PTSD severity,
      childhood sexual trauma, and age remained significant in multivariable GEE
      models. The PTSD symptom cluster re-experiencing was most strongly associated
      with CSB. DISCUSSION: This exploratory study suggests that CSB is prevalent
      amongst veterans returning from combat and is associated with childhood trauma
      and PTSD, particularly re-experiencing. CONCLUSIONS: Further study is needed to
      identify the mechanisms linking PTSD and CSB, define the context and severity of
      CSB in veterans, and examine the best ways to assess and treat CSB in VA clinical
      settings.

PMID- 25592307
TI  - Could music potentially serve as a functional alternative to alcohol consumption?
      The importance of music motives among drinking and non-drinking adolescents.
AB  - BACKGROUND AND AIMS: This study investigated whether adolescents who drink and
      those who are teetotal differ in the link between music motives and health
      related outcomes (life satisfaction, self-rated health, school pressure, somatic
      complaints, depressed and aggressive mood, physical powerlessness, frequency of
      being bullied and bullying others and evenings spent out with friends). It also
      looked at whether associations between music motives and health-related outcomes
      remained significant when drinking motives were included among drinkers. METHODS:
      Confirmatory factor analysis and structural equation models were estimated based
      on data from 4,481 adolescents from Switzerland (mean age 14.5, SD = 0.9).
      RESULTS: It was confirmed that the four music motives and the four drinking
      motives obtained by crossing the valence (positive-negative) and the source
      (internal-external) of expected change in affect form distinct dimensions (i.e.
      the 8-factor model best fitted the data). Drinkers and non-drinkers differed in
      the various links between music motives and health-related outcomes. For example,
      almost all the links between conformity music motives and the health-related
      outcomes were significant for non-drinkers but not for drinkers. Enhancement
      music motives, by contrast, were often significant for drinkers but not for non
      drinkers. Coping music motives were significant among both drinkers and non
      drinkers. These links were basically unchanged when drinking motives were taken
      into account. DISCUSSION AND CONCLUSIONS: This study indicates that music serves
      important functions in the lives of adolescents, even among those who use alcohol
      for different motives. This makes listening to music a promising potential
      alternative to alcohol use.

PMID- 25592308
TI  - Understanding the role of shame and its consequences in female hypersexual
      behaviours: a pilot study.
AB  - BACKGROUND AND AIMS: Hypersexuality and sexual addiction among females is a
      little understudied phenomenon. Shame is thought to be intrinsic to hypersexual
      behaviours, especially in women. Therefore, the aim of this study was to
      understand both hypersexual behaviours and consequences of hypersexual behaviours
      and their respective contributions to shame in a British sample of females (n =
      102). METHODS: Data were collected online via Survey Monkey. RESULTS: Results
      showed the Sexual Behaviour History (SBH) and the Hypersexual Disorder
      Questionnaire (HDQ) had significant positive correlation with scores on the Shame
      Inventory. The results indicated that hypersexual behaviours were able to predict
      a small percentage of the variability in shame once sexual orientation
      (heterosexual vs. non-heterosexual) and religious beliefs (belief vs. no belief)
      were controlled for. Results also showed there was no evidence that religious
      affiliation and/or religious beliefs had an influence on the levels of
      hypersexuality and consequences of sexual behaviours as predictors of shame.
      CONCLUSIONS: While women in the UK are rapidly shifting to a feminist way of
      thinking with or without technology, hypersexual disorder may often be
      misdiagnosed and misunderstood because of the lack of understanding and how it is
      conceptualised. The implications of these findings are discussed.

PMID- 25592309
TI  - Different facets of compulsive buying among Chinese students.
AB  - BACKGROUND AND AIMS: Compulsive buying is a severe phenomenon, especially among
      younger consumers. It is well documented in Western industrial societies like the
      USA and Germany, and nowadays an increasing interest in compulsive buying in non
      Western countries is on the rise. METHODS: In the current study, we measured the
      prevalence of compulsive buying tendencies among Chinese female and male students
      by using a Chinese translation of the German Compulsive Buying Scale (Raab,
      Neuner, Reisch & Scherhorn, 2005). We examined the influence of gender, location
      and age using ANCOVA, and binary logistic regression. RESULTS: Factor analysis
      identified three factorial dimensions of compulsive buying tendencies which are
      impairment of impulse control and reactive or compensatory aspects, reduced
      rationality according to money spending, and post-purchase guilt. Our results
      indicated that about 6.7% of the sample shows a compulsive buying pattern, and
      that females are more affected. For location, a geographic difference between
      Chongqing and Fuzhou was found for the overall compulsive tendencies, but not for
      the percentages of compulsive buyers. CONCLUSIONS: In sum, the existing study
      provides evidence that Chinese consumers have a factorial structure which differs
      somewhat in compulsive buying from Western samples. Observations about gender and
      location were considered. These findings give a deeper understanding of China's
      compulsive buying behavior.

PMID- 25592312
TI  - Erratum to: Gamblers seeking treatment: Who does and who doesn't?

PMID- 25592310
TI  - Similarities and differences among Internet gaming disorder, gambling disorder
      and alcohol use disorder: a focus on impulsivity and compulsivity.
AB  - BACKGROUND AND AIMS: The aim of the present study was to test the impulsivities
      and compulsivities of behavioral addictions, including Internet gaming disorder
      (IGD) and gambling disorder (GD), by directly comparing them with alcohol use
      disorder (AUD) and a healthy control (HC) group. METHODS: We enrolled male
      patients who were diagnosed with IGD, GD or AUD, with 15 patients per group, as
      well as 15 HCs. Trait impulsivity was measured using the Barratt Impulsiveness
      Scale version 11 (BIS-11). The stop-signal test (SST) from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB) was used to assess the
      patients' abilities to inhibit prepotent responses. Compulsivity was measured
      using the intra-extra dimensional set shift (IED) test from the CANTAB. The Trail
      Making Test (TMT) was also used in this study. RESULTS: The IGD and AUD groups
      scored significantly higher on the BIS-11 as a whole than did the HC group (p =
      0.001 and p = 0.001, respectively). The IGD and AUD groups also scored
      significantly higher on the BIS-11 as a whole than did the GD group (p = 0.006
      and p = 0.001, respectively). In addition, the GDgroup made significantly more
      errors (p = 0.017 and p = 0.022, respectively) and more individuals failed to
      achieve criterion on the IED test compared with the IGD and HC groups (p = 0.018
      and p = 0.017, respectively). Discussion: These findings may aid in the
      understanding of not only the differences in categorical aspects between
      individuals with IGD and GD but also in impulsivity-compulsivity dimensional
      domains. CONCLUSION: Additional studies are needed to elucidate the
      neurocognitive characteristics of behavioral addictive disorders in terms of
      impulsivity and compulsivity.

PMID- 25592313
TI  - Pollux: platform independent error correction of single and mixed genomes.
AB  - BACKGROUND: Second-generation sequencers generate millions of relatively short,
      but error-prone, reads. These errors make sequence assembly and other downstream
      projects more challenging. Correcting these errors improves the quality of
      assemblies and projects which benefit from error-free reads. RESULTS: We have
      developed a general-purpose error corrector that corrects errors introduced by
      Illumina, Ion Torrent, and Roche 454 sequencing technologies and can be applied
      to single- or mixed-genome data. In addition to correcting substitution errors,
      we locate and correct insertion, deletion, and homopolymer errors while remaining
      sensitive to low coverage areas of sequencing projects. Using published data
      sets, we correct 94% of Illumina MiSeq errors, 88% of Ion Torrent PGM errors, 85%
      of Roche 454 GS Junior errors. Introduced errors are 20 to 70 times more rare
      than successfully corrected errors. Furthermore, we show that the quality of
      assemblies improves when reads are corrected by our software. CONCLUSIONS: Pollux
      is highly effective at correcting errors across platforms, and is consistently
      able to perform as well or better than currently available error correction
      software. Pollux provides general-purpose error correction and may be used in
      applications with or without assembly.

PMID- 25592314
TI  - Processes of behavior change and weight loss in a theory-based weight loss
      intervention program: a test of the process model for lifestyle behavior change.
AB  - BACKGROUND: Process evaluation is important for improving theories of behavior
      change and behavioral intervention methods. The present study reports on the
      process outcomes of a pilot test of the theoretical model (the Process Model for
      Lifestyle Behavior Change; PMLBC) underpinning an evidence-informed, theory
      driven, group-based intervention designed to promote healthy eating and physical
      activity for people with high cardiovascular risk. METHODS: 108 people at high
      risk of diabetes or heart disease were randomized to a group-based weight
      management intervention targeting diet and physical activity plus usual care, or
      to usual care. The intervention comprised nine group based sessions designed to
      promote motivation, social support, self-regulation and understanding of the
      behavior change process. Weight loss, diet, physical activity and theoretically
      defined mediators of change were measured pre-intervention, and after four and 12
      months. RESULTS: The intervention resulted in significant improvements in fiber
      intake (M between-group difference = 5.7 g/day, p < .001) but not fat consumption
      (-2.3 g/day, p = 0.13), that were predictive of weight loss at both four months
      (M between-group difference = -1.98 kg, p < .01; R(2) = 0.2, p < 0.005), and 12
      months (M difference = -1.85 kg, p = 0.1; R(2) = 0.1, p < 0.01). The intervention
      was successful in improving the majority of specified mediators of behavior
      change, and the predicted mechanisms of change specified in the PMBLC were
      largely supported. Improvements in self-efficacy and understanding of the
      behavior change process were associated with engagement in coping planning and
      self-monitoring activities, and successful dietary change at four and 12 months.
      While participants reported improvements in motivational and social support
      variables, there was no effect of these, or of the intervention overall, on
      physical activity. CONCLUSIONS: The data broadly support the theoretical model
      for supporting some dietary changes, but not for physical activity. Systematic
      intervention design allowed us to identify where improvements to the intervention
      may be implemented to promote change in all proposed mediators. More work is
      needed to explore effective mechanisms within interventions to promote physical
      activity behavior.

PMID- 25592316
TI  - Most screening tests do not save lives, researchers argue.

PMID- 25592315
TI  - Severe gastrointestinal dysmotility developed after treatment with gonadotropin
      releasing hormone analogs.
AB  - BACKGROUND: Sporadic cases of abdominal pain and dysmotility has been described
      after treatment with gonadotropin-releasing hormone (GnRH) analogs. The aim of
      the present study was to scrutinize for patients with severe gastrointestinal
      complaints after treatment with GnRH analogs, to describe the expression of
      antibodies against progonadoliberin-2, GnRH1, GnRH receptor (GnRHR), luteinizing
      hormone (LH), and LH receptor in serum in these patients, and to search for
      possible triggers and genetic factors behind the development of this dysmotility.
      METHODS: Patients suffering from prolonged gastrointestinal complaints after
      treatment with GnRH analogs at the Department of Gastroenterology, Skane
      University Hospital, were included. GnRHR and LH receptor (LHCGR) genes were
      exome-sequenced. Serum was analyzed by enzyme-linked immune sorbent assays for
      the presence of antibodies. Healthy blood donors and women treated with GnRH
      analogs because of in vitro fertilization (IVF) were used as controls. RESULTS:
      Seven patients with severe gastrointestinal complaints after GnRH treatment were
      identified, of whom six suffered from endometriosis. Several variants were found
      within the 11 exons of LHCGR. The minor allele G, at the single nucleotide
      polymorphism rs6755901, was detected in homozygosity in two patients (28.5%) who
      had developed chronic intestinal pseudo-obstruction and in 5.5% of the IVF
      controls. Three patients expressed IgM antibodies against progonadoliberin-2 and
      three against GnRH1 (42.9%) when cut off was set to a titer >97.5th percentile in
      blood donors. CONCLUSION: A high prevalence of endometriosis, polymorphism in the
      LHCGR and GnRH1 and progonadoliberin-2 antibodies in serum was found among the
      patients with severe dysmotility after treatment with GnRH analogs.

PMID- 25592317
TI  - Pharmacological lineage analysis revealed the binding affinity of broad-spectrum
      substance P antagonists to receptors for gonadotropin-releasing peptide.
AB  - A group of synthetic substance P (SP) antagonists, such as [Arg(6),D
      Trp(7,9),N(Me)Phe(8)]-substance P(6-11) and [D-Arg(1),D-Phe(5),D
      Trp(7,9),Leu(11)]-substance P, bind to a range of distinct G-protein-coupled
      receptor (GPCR) family members, including V1a vasopressin receptors, and they
      competitively inhibit agonist binding. This extended accessibility enabled us to
      identify a GPCR subset with a partially conserved binding site structure. By
      combining pharmacological data and amino acid sequence homology matrices, a
      pharmacological lineage of GPCRs that are sensitive to these two SP antagonists
      was constructed. We found that sensitivity to the SP antagonists was not limited
      to the Gq-protein-coupled V1a and V1b receptors; Gs-coupled V2 receptors and
      oxytocin receptors, which couple with both Gq and Gi, also demonstrated
      sensitivity. Unexpectedly, a dendrogram based on the amino acid sequences of 222
      known GPCRs showed that a group of receptors sensitive to the SP antagonists are
      located in close proximity to vasopressin/oxytocin receptors. Gonadotropin
      releasing peptide receptors, located near the vasopressin receptors in the
      dendrogram, were also sensitive to the SP analogs, whereas alpha1B adrenergic
      receptors, located more distantly from the vasopressin receptors, were not
      sensitive. Our finding suggests that pharmacological lineage analysis is useful
      in selecting subsets of candidate receptors that contain a conserved binding site
      for a ligand with broad-spectrum binding abilities. The knowledge that the
      binding site of the two broad-spectrum SP analogs partially overlaps with that of
      distinct peptide agonists is valuable for understanding the specificity/broadness
      of peptide ligands. 

PMID- 25592318
TI  - Platycodin D triggers autophagy through activation of extracellular signal
      regulated kinase in hepatocellular carcinoma HepG2 cells.
AB  - Platycodin D (PD), isolated from the Chinese medicinal herb named Platycodonis
      Radix, is a triterpenoid saponin with well-known anti-tumor effects. In this
      study, we provided reliable evidence that PD triggered autophagy in a number of
      cell lines in vitro. PD-triggered autophagy was identified by observation of
      cytoplasmic vacuole, up-regulation of microtubule-associated protein 1 light
      chain 3 II (LC3-II), and accumulation of autophagosomes. The Akt/mammalian target
      of rapamycin (mTOR) pathway may be not involved in PD-triggered autophagy, as
      evidenced by the increased phosphorylation of Akt (Thr308), mTOR (Ser2448),
      ribosomal protein S6 kinase (Ser371), and ULK1 (Ser757). However, the
      extracellular signal-regulated kinase (ERK) was activated after PD treatment. The
      decreased ERK phosphorylation caused by pretreatment with U0126, an inhibitor of
      MEK, suppressed the expression of LC3-II compared with PD treatment alone,
      suggesting that ERK pathway may have a critical function in PD-triggered
      autophagy. In addition, the PD-induced proliferative inhibition and apoptosis
      were enhanced when pretreatment with autophagy inhibitor chloroquine (CQ) or
      bafilomycin A1 (BAF), indicating that PD may trigger a protective autophagy in
      HepG2 cells. To the best of our knowledge, this paper is the first to report that
      PD triggers autophagy in a series of cell lines and ERK activation is important
      for PD-triggered autophagy in hepatocellular carcinoma HepG2 cells. The combined
      treatment with PD and CQ or BAF may be a promising regimen for hepatocellular
      carcinoma treatment. 

PMID- 25592319
TI  - High-throughput analysis of behavior for drug discovery.
AB  - Drug testing with traditional behavioral assays constitutes a major bottleneck in
      the development of novel therapies. PsychoGenics developed three comprehensive
      high-throughput systems, SmartCube((r)), NeuroCube((r)) and PhenoCube((r))
      systems, to increase the efficiency of the drug screening and phenotyping in
      rodents. These three systems capture different domains of behavior, namely,
      cognitive, motor, circadian, social, anxiety-like, gait and others, using custom
      built computer vision software and machine learning algorithms for analysis. This
      review exemplifies the use of the three systems and explains how they can advance
      drug screening with their applications to phenotyping of disease models, drug
      screening, selection of lead candidates, behavior-driven lead optimization, and
      drug repurposing. 

PMID- 25592320
TI  - The many different faces of major depression: it is time for personalized
      medicine.
AB  - First line antidepressants are the so-called SSRIs (selective serotonin reuptake
      inhibitors), e.g. fluvoxamine, fluoxetine, sertraline, paroxetine and
      escitalopram. Unfortunately, these drugs mostly do not provide full symptom
      relief and have a slow onset of action. Therefore other antidepressants are also
      being prescribed that inhibit the reuptake of norepinephrine (e.g. reboxetine,
      desipramine) or the reuptake of both serotonin (5-HT) and norepinephrine (e.g.
      venlafaxine, duloxetine, milnacipran). Nevertheless, many patients encounter
      residual symptoms such as impaired pleasure, impaired motivation, and lack of
      energy. It is hypothesized that an impaired brain reward system may underlie
      these residual symptoms. In agreement, there is some evidence that reuptake
      inhibitors of both norepinephrine and dopamine (e.g. methylphenidate, bupropion,
      nomifensine) affect these residual symptoms. In the pipeline are new drugs that
      block all three monoamine transporters for the reuptake of 5-HT, norepinephrine
      and dopamine, the so-called triple reuptake inhibitors (TRI). The working
      mechanisms of the above-mentioned antidepressants are discussed, and it is
      speculated whether depressed patients with different symptoms, sometimes even
      opposite ones due to atypical or melancholic features, can be matched with the
      different drug treatments available. In other words, is personalized medicine for
      major depression an option in the near future? 

PMID- 25592321
TI  - Blockade of NMDA receptors reverses the depressant, but not anxiogenic effect of
      adolescence social isolation in mice.
AB  - Early life social isolation stress (SIS), a well-known chronic stress paradigm,
      is contributed to a number of pathophysiological and neurochemical changes
      including depression and anxiety. The underlying mechanisms for these disorders
      in socially isolated animals have not been fully cleared. Previous studies have
      shown that N-Methyl-d-aspartate (NMDA) receptor function is changed by social
      isolation condition. It is now well recognized that NMDA receptor blockade can
      exhibit antidepressant and anxiolytic actions. In our study, postnatal day 21-25
      mice were randomly housed for 4 weeks under either social condition (SC) or
      isolated condition (IC). Then, animals were subjected to different behavioral
      experiments to investigate whether blockade of NMDA receptor resulted in
      behavioral alterations in animals. Social isolation stress induced depressive and
      anxiety-like behaviors in IC animals in comparison with SC mice. Also, we applied
      subeffective doses of antagonists including ketamine (1mg/kg), MK-801
      (0.05mg/kg), and magnesium sulfate (10mg/kg) to both SC and IC mice prior to
      behavioral experiments. Administration of a single dose of all mentioned drugs
      did not affect the SC mice but modulated the depressant effects of SIS on IC
      mice. Administration of NMDA receptor antagonists decreased the immobility time
      in the forced swimming test as well as an increase in grooming behavior in splash
      test. However, anxiety-like behaviors in IC animals remained unchanged in hole
      board test and open field test after blockade of NMDA receptors. Taken together,
      our results showed the possible involvement of the NMDA receptors in the
      depressive, but not anxiety-like behaviors induced by SIS. 

PMID- 25592323
TI  - Rotundarpene attenuates cholesterol oxidation product-induced apoptosis by
      suppressing the mitochondrial pathway and the caspase-8- and bid-dependent
      pathways.
AB  - The extract of from the barks of Ilex Rotunda Thunb has demonstrated anti
      inflammatory and anti-oxidant effects. Nevertheless, the effect of rotundarpene
      (4-caffeoyl-3-methyl-but-2-ene-1,4-diol) on the neuronal cell death induced by
      cholesterol oxidation products is unclear. We assessed the preventive effect of
      rotundarpene on the cholesterol oxidation product-induced apoptosis in neuronal
      cells using differentiated PC12 cells. 7-Ketocholesterol and 25
      hydroxycholesterol induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein
      levels, increase in Bax levels, loss of the mitochondrial transmembrane
      potential, cytochrome c release, activation of caspases (-8, -9 and -3), cleavage
      of PARP-1 and an increase in the tumor suppressor p53 levels. Rotundarpene
      attenuated the cholesterol oxidation product-induced changes in the apoptosis
      related protein levels, formation of reactive oxygen species, depletion of GSH,
      nuclear damage and cell death. The results show that rotundarpene may attenuate
      the cholesterol oxidation product-induced apoptosis in PC12 cells by suppressing
      the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent
      pathways. The preventive effect appears to be attributed to its inhibitory effect
      on the formation of reactive oxygen species and depletion of GSH. Rotundarpene
      appears to attenuate cholesterol-oxidation product-mediated neuronal
      degeneration. 

PMID- 25592322
TI  - Role of eukaryotic translation initiation factor 3a in bleomycin-induced
      pulmonary fibrosis.
AB  - Eukaryotic translation initiation factor 3a (eIF3a) is a multifunctional protein
      and plays an important role in regulation of cellular function including
      proliferation and differentiation. In the present study, we tested the function
      of eIF3a in pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal
      instillation of bleomycin (5mg/kg) in rats. Primary pulmonary fibroblasts were
      cultured for proliferation investigation by BrdU incorporation method and flow
      cytometry. The expression/level of eIF3a, TGF-beta1, ERK1/2 and alpha-SMA were
      analyzed by ELISA, real-time PCR or western blot. Results showed that the
      expression of eIF3a was obviously increased in lungs of pulmonary fibrosis rats
      accompanied by up-regulation of alpha-SMA and collagens. In cultured pulmonary
      fibroblasts, application of exogenous TGF-beta1 induced cell proliferation and
      differentiation concomitantly with up-regulation of eIF3a expression and ERK1/2
      phosphorylation. The effects of TGF-beta1-induced proliferation of fibroblasts
      and up-regulation of alpha-SMA were abolished by eIF3a siRNA. TGF-beta1-induced
      eIF3a expression was reversed in the presence of PD98059, an inhibitor of ERK1/2.
      These findings suggest that eIF3a plays an important role in bleomycin-induced
      pulmonary fibrosis by regulating pulmonary fibroblasts' function, and up
      regulation of eIF3a induced by TGF-beta1 is mediated via the ERK1/2 pathway. 

PMID- 25592324
TI  - Rapid conversion of the ester prodrug abiraterone acetate results in intestinal
      supersaturation and enhanced absorption of abiraterone: in vitro, rat in situ and
      human in vivo studies.
AB  - The aim of this study was to evaluate the intestinal disposition of abiraterone
      acetate, an ester prodrug of the anticancer agent abiraterone. Stability of the
      prodrug and solubility and dissolution characteristics of both abiraterone and
      abiraterone acetate were monitored in vitro. Moreover, the in vivo intraluminal
      concentrations of abiraterone and abiraterone acetate upon intake of one tablet
      of 250 mg abiraterone acetate were assessed in healthy volunteers. The intestinal
      absorption resulting from the intraluminal behavior of the ester prodrug was
      determined using the rat in situ intestinal perfusion technique with mesenteric
      blood sampling. Simulated and aspirated human intestinal fluids of the fasted
      state were used as solvent systems. Upon incubation of abiraterone acetate in
      human intestinal fluids in vitro, rapid hydrolysis of the prodrug was observed,
      generating abiraterone concentrations largely exceeding the apparent solubility
      of abiraterone, suggesting the existence of intestinal supersaturation. These
      findings were confirmed in vivo, by intraluminal sampling of duodenal fluids upon
      oral intake of an abiraterone acetate tablet by healthy volunteers. Rat in situ
      intestinal perfusion experiments performed with suspensions of abiraterone and
      abiraterone acetate in human intestinal fluids of the fasted state revealed
      significantly higher flux values upon perfusion with the prodrug than with
      abiraterone. Moreover, rat in situ intestinal perfusion with abiraterone acetate
      suspensions in simulated fluids of the fasted state in presence or absence of
      esterases demonstrated that increased hydrolytic activity of the perfusion medium
      was beneficial to the intestinal absorption of abiraterone. In conclusion, the
      rapid hydrolysis of abiraterone acetate in the intraluminal environment appears
      to result in fast and extensive generation of abiraterone supersaturation,
      creating a strong driving force for abiraterone absorption.

PMID- 25592326
TI  - Silk hydrogels for sustained ocular delivery of anti-vascular endothelial growth
      factor (anti-VEGF) therapeutics.
AB  - Silk hydrogels were formulated with anti-vascular endothelial growth factor (anti
      VEGF) therapeutics for sustained ocular drug delivery. Using silk fibroin as a
      vehicle for delivery, bevacizumab-loaded hydrogel formulations demonstrated
      sustained release of 3 months or greater in experiments in vitro as well as in
      vivo using an intravitreal injection model in Dutch-belted rabbits. Using both
      standard dose (1.25mg bevacizumab/50 MUL injection) and high dose (5.0mg
      bevacizumab/50 MUL injection) hydrogel formulations, release concentrations were
      achieved at day 90 that were equivalent or greater than those achieved at day 30
      with the positive standard dose control (single injection (50 MUL) of 1.25mg
      bevacizumab solution), which is estimated to be the therapeutic threshold based
      on the current dosage administration schedule of 1 injection/month. These gels
      also demonstrated signs of biodegradation after 3 months, suggesting that
      repeated injections may be possible (e.g., one injection every 3-6 months or
      longer). Due to its pharmacokinetic and biodegradation profiles, this delivery
      system may be used to reduce the frequency of dosing for patients currently
      enduring treatment using bevacizumab or other anti-VEGF therapeutics.

PMID- 25592327
TI  - Surgical management of hyperthyroidism.
AB  - AIMS: Hyperthyroidism includes several clinical and histopathological situations.
      Surgery is commonly indicated after failure of medical treatment. The aim of this
      study was to analyze the indications and complications of surgery as well as
      endocrine results. MATERIALS AND METHODS: Patients operated on for
      hyperthyroidism between 2004 and 2012 were included in a retrospective study.
      Total thyroidectomy was performed for Graves' disease, toxic multinodular goiter
      and amiodarone-associated thyrotoxicosis; patients with toxic nodule underwent
      hemithyroidectomy. Pathologic analysis assessed surgical specimens; postoperative
      complications and resolution of hyperthyroidism were noted. RESULTS: Two hundred
      patients from 15 to 83 years old were included. One hundred and eighty-eight
      underwent primary surgery and 12 were re-operated for recurrent goiter (6 with
      subtotal thyroidectomy for multinodular goiter 25 years previously; 6 with
      hemithyroidectomy for solitary nodule 15 years previously). Eighty-two patients
      suffered from toxic multinodular goiter, 78 from Graves' disease, 35 from
      solitary toxic nodules and 5 from amiodarone-associated thyrotoxicosis. Fourteen
      papillary carcinomas (including 11 papillary microcarcinomas) and 34 healthy
      parathyroid glands (17%) were identified in the pathological specimens.
      Postoperative complications comprised 4% permanent recurrent laryngeal nerve
      palsy (1 year follow-up), 9% hematoma requiring surgical revision, and 3%
      definitive hypocalcemia. Normalization of thyroid hormone levels was observed in
      198 patients. Two recurrences occurred due to incomplete resection (1 case of
      Graves' disease and 1 intrathoracic toxic goiter that occurred respectively 18
      and 5 months after resection). Postoperative complications were more frequent in
      multinodular goiter (23%) than in Graves' disease (13%) (ns: P>0.05). CONCLUSION:
      Surgical management of hyperthyroidism enables good endocrinal control if surgery
      is complete. Patients need to be fully informed of all possible postoperative
      complications that could occur, especially vocal ones. Long-term follow-up is
      necessary to detect recurrence, which can occur more than 20 years after partial
      thyroidectomy surgery. Surgery allows early diagnosis of 12.5% of papillary
      carcinomas.

PMID- 25592328
TI  - Quantification of 8-alpha-hydroxy-mutilin as marker residue for tiamulin in
      rabbit tissues by high-performance liquid chromatography-mass spectrometry.
AB  - For the first time, a sensitive and specific method was developed and fully
      validated for the quantification of the EU marker residue of tiamulin, 8-alpha
      hydroxy-mutilin, in rabbit muscle and liver tissues using liquid chromatography
      combined with positive heated electrospray ionization triple quadrupole mass
      spectrometry. The mass spectrometer was operated in the selected reaction
      monitoring (SRM) mode with selection of the [M + H](+) ion in both quadrupoles 1
      and 3, resulting in the SRM transition m/z 337.25 > 337.25 for quantification.
      Chromatography was performed using a Hypersil Gold C18 column using a gradient
      elution program with water and methanol as mobile phases. The sample preparation
      procedure for the analysis of 8-alpha-hydroxy-mutilin in liver and muscle samples
      consisted of three main steps: (1) extraction of the tissue matrix using 0.1 N
      hydrochloric acid/acetone (50/50, v/v), (2) hydrolysis of tiamulin and
      metabolites to 8-alpha-hydroxy-mutilin in alkaline medium at 45  degrees C, and
      (3) liquid-liquid extraction in acidic medium using ethyl acetate. This is the
      first method presenting fully validated results, encompassing a linearity of 50
      to 2,000 MUg/kg, within-run and between-run accuracy and precision, limit of
      quantification (50 MUg/kg for both muscle and liver tissues), limit of detection
      (muscle, 11.9 MUg/kg; liver, 20.6 MUg/kg), extraction recovery (muscle, 66.2%;
      liver, 75.5%), signal suppression and enhancement (muscle, 51.7%; liver, 43.3%),
      carryover, applicability and practicability, and stability during storage and
      analysis. This novel method is therefore sensitive enough to be used for residue
      depletion studies of tiamulin in rabbits and for food safety monitoring with
      respect to MRL compliance of residues.

PMID- 25592330
TI  - Hyponatremia: A Review.
AB  - Hyponatremia is the most frequently occurring electrolyte abnormality and can
      lead to life-threatening complications. This disorder may be present on admission
      to the intensive care setting or develop during hospitalization as a result of
      treatment or multiple comorbidities. Patients with acute hyponatremia or
      symptomatic chronic hyponatremia will likely require treatment in the intensive
      care unit (ICU). Immediate treatment with hypertonic saline is needed to reduce
      the risk of permanent neurologic injury. Chronic hyponatremia should be corrected
      at a rate sufficient to reduce symptoms but not at an excessive rate that would
      create a risk of osmotic injury. Determination of the etiology of chronic
      hyponatremia requires analysis of serum osmolality, volume status, and urine
      osmolality and sodium level. Correct diagnosis points to the appropriate
      treatment and helps identify risk factors for accelerated correction of the serum
      sodium level. Management in the ICU facilitates frequent laboratory draws and
      allows close monitoring of the patient's mentation as well as quantification of
      urine output. Overly aggressive correction of serum sodium levels can result in
      neurological injury caused by osmotic demyelination. Therapeutic measures to
      lower the serum sodium level should be undertaken if the rate increases too
      rapidly. 

PMID- 25592329
TI  - Herbivore associated elicitor-induced defences are highly specific among closely
      related Nicotiana species.
AB  - BACKGROUND: Herbivore-induced defence responses are often specific - different
      herbivores induce different defence responses in plants - and their specificity
      is largely mediated by chemical cues (herbivore-associated elicitors: HAEs) in
      insect oral or oviposition secretions. However, the specificity and the
      mechanisms of HAE-induced defence have not been investigated in the context of
      the evolutionary relationships among plant species. Here we compare the responses
      of six closely related Nicotiana species to a synthetic elicitor, N-linolenoyl
      glutamic acid (C18:3-Glu) and HAE of two insect herbivores (the Solanaceae
      specialist Manduca sexta and generalist Spodoptera littoralis). RESULTS: HAE
      induced defences are highly specific among closely related Nicotiana species at
      three perspectives. 1) A single Nicotiana species can elicit distinct responses
      to different HAEs. N. pauciflora elicited increased levels of JA and trypsin
      proteinase inhibitors (TPI) in response to C18:3-Glu and the oral secretions of
      M. sexta (OS Ms ) but not to oral secretions of S. littoralis (OS Sl ). In
      contrast, N. miersii only responded to OS Sl but not to the other two HAEs. The
      specific responses to different HAEs in Nicotiana species are likely due to the
      perception by the plant of each specific component of the HAE. 2) One HAE can
      induce different defence responses among closely related Nicotiana species. OS Ms
      and C18:3-Glu induced JA and TPI accumulations in N. linearis, N. attenuata, N.
      acuminata and N. pauciflora, but not in N. miersii and N. obtusifolia. 3) The
      effect of HAE-induced defences differ for the Solanaceae specialist M. sexta and
      the generalist S. littoralis. Among the four tested Nicotiana species, while the
      growth rate of M. sexta was only reduced by the induced defences elicited by
      C18:3-Glu; the growth rate of S. littoralis can be reduced by the induced
      defences elicited by all three HAEs. This is likely due to differences in the
      susceptibility of the specialist M. sexta and generalist S. littoralis to induced
      defences of their host. CONCLUSIONS: Closely related Nicotiana species elicit
      highly specific defence responses to herbivore associated elicitors and provide
      an ideal framework for investigating the molecular mechanisms and evolutionary
      divergence of induced resistance in plants.

PMID- 25592331
TI  - The shortened infusion time of intravenous ibuprofen, part 2: a multicenter, open
      label, surgical surveillance trial to evaluate safety.
AB  - PURPOSE: The literature and clinical data support the use of intravenous (IV)
      infusions of ibuprofen to control pain and reduce the opioid requirements
      associated with surgical pain. According to current guidelines, IV ibuprofen can
      be administered via a slow IV infusion performed during a 30-minute period.
      Although recent studies indicate that more rapid infusions may yield additional
      benefits for patients, the safety of such an approach needs further evaluation.
      The main purpose of this study was to determine the safety of single and multiple
      doses of IV ibuprofen (800 mg) administered over 5 to 10 minutes at the induction
      of anesthesia and after the surgical procedure for the treatment of postoperative
      pain. METHODS: This was a Phase IV, multicenter, open-label, clinical
      surveillance study. It was conducted at 21 hospitals in the United States, and
      300 adult hospitalized patients undergoing surgery were enrolled. The exclusion
      criteria for the study were: inadequate IV access; hypersensitivity to any
      component of IV ibuprofen, aspirin, or related products; and any active,
      clinically significant bleeding. Also excluded were patients who had taken NSAIDs
      <6 hours before administration of IV ibuprofen; pregnant or breastfeeding female
      patients; and patients in the perioperative period of coronary artery bypass
      graft surgery. Patients received 800 mg of IV ibuprofen administered over 5 to 10
      minutes preoperatively. Vital signs, adverse events, and pain scores were
      assessed. FINDINGS: Approximately 22% (65 of 300) of patients reported adverse
      events (serious and nonserious). The most common adverse event was infusion site
      pain (34 of 300 [11%]). No deaths were reported. Nine subjects reported serious
      adverse events, 8 of which occurred during the first 6 hours. All serious events
      reported were judged unrelated to ibuprofen. Of the 300 total patients, 2 (0.67%)
      discontinued the study drug due to an adverse event (1 patient discontinued the
      study because of infusion site pain, and 1 patient withdrew due to a
      hypersensitivity reaction after drug administration). IMPLICATIONS: Our study
      found that IV ibuprofen infused over 5 to 10 minutes at induction of anesthesia
      is a safe administration option for surgical patients. ClinicalTrials.gov
      identifier: NCT01334957.

PMID- 25592325
TI  - Nanoparticle-based technologies for retinal gene therapy.
AB  - For patients with hereditary retinal diseases, retinal gene therapy offers
      significant promise for the prevention of retinal degeneration. While adeno
      associated virus (AAV)-based systems remain the most popular gene delivery method
      due to their high efficiency and successful clinical results, other delivery
      systems, such as non-viral nanoparticles (NPs) are being developed as additional
      therapeutic options. NP technologies come in several categories (e.g., polymer,
      liposomes, peptide compacted DNA), several of which have been tested in mouse
      models of retinal disease. Here, we discuss the key biochemical features of the
      different NPs that influence how they are internalized into cells, escape from
      endosomes, and are delivered into the nucleus. We review the primary mechanism of
      NP uptake by retinal cells and highlight various NPs that have been successfully
      used for in vivo gene delivery to the retina and RPE. Finally, we consider the
      various strategies that can be implemented in the plasmid DNA to generate
      persistent, high levels of gene expression. 

PMID- 25592333
TI  - Hepatitis C virus of subtype 2l in Marseille, southeastern France.
AB  - The rate of eradication of chronic hepatitis C considerably increases with direct
      acting antiviral agents, particularly hepatitis C virus (HCV) polymerase
      inhibitors. While implementing full-length HCV NS5B polymerase sequencing in our
      clinical microbiology laboratory, we identified atypical HCV sequences,
      classified as subtype 2l, from 2 patients. HCV-2l NS5B polymerase sequences were
      detected from 5 and 14 additional patients by screening our laboratory hepatitis
      virus sequence database and the NCBI GenBank sequence database. Phylogenetic
      analyses show unambiguously that all HCV-2l sequences are clustered apart from
      HCV 2 non-l sequences, which compose a second cluster. Mean (+/-SD) nucleotide
      identity between near full-length NS5B fragments of subtype 2l was 93.4 +/- 0.8%
      (range: 92.4-95.1). Of note, all HCV-2l sequences obtained in our laboratory and
      in other centers were from serum samples collected in France. Analysis of the HCV
      2l NS5B polymerase amino acid sequences at 30 positions critical for interaction
      with or resistance to HCV polymerase inhibitors showed specific patterns.

PMID- 25592332
TI  - Treating tobacco use disorder in pregnant women in medication-assisted treatment
      for an opioid use disorder: a systematic review.
AB  - Smoking is associated with adverse effects on pregnancy and fetal development,
      yet 88-95% of pregnant women in medication-assisted treatment for an opioid use
      disorder smoke cigarettes. This review summarizes existing knowledge about
      smoking cessation treatments for pregnant women on buprenorphine or methadone,
      the two forms of medication-assisted treatment for opioid use disorder indicated
      for prenatal use. We performed a systematic review of the literature using
      indexed terms and key words to capture the concepts of smoking, pregnancy, and
      opioid substitution and found that only three studies met search criteria.
      Contingency management, an incentive based treatment, was the most promising
      intervention: 31% of participants achieved abstinence within the 12-week study
      period, compared to 0% in a non-contingent behavior incentive group and a group
      receiving usual care. Two studies of brief behavioral interventions resulted in
      reductions in smoking but not cessation. Given the growing number of pregnant
      women in medication-assisted treatment for an opioid use disorder and the
      negative consequences of smoking on pregnancy, further research is needed to
      develop and test effective cessation strategies for this group. 

PMID- 25592334
TI  - Broad functional correction of molecular impairments by systemic delivery of
      scAAVrh74-hSGSH gene delivery in MPS IIIA mice.
AB  - Mucopolysaccharidosis (MPS) IIIA is a neuropathic lysosomal storage disease
      caused by deficiency in N-sulfoglucosamine sulfohydrolase (SGSH). Genome-wide
      gene expression microarrays in MPS IIIA mice detected broad molecular
      abnormalities (greater than or equal to twofold, false discovery rate <=10) in
      numerous transcripts (314) in the brain and blood (397). Importantly, 22
      dysregulated blood transcripts are known to be enriched in the brain and linked
      to broad neuronal functions. To target the root cause, we used a self
      complementary AAVrh74 vector to deliver the human SGSH gene into 4-6 weeks old
      MPS IIIA mice by an intravenous injection. The treatment resulted in global
      central nervous system (CNS) and widespread somatic restoration of SGSH activity,
      clearance of CNS and somatic glycosaminoglycan storage, improved behavior
      performance, and significantly extended survival. The scAAVrh74-hSGSH treatment
      also led to the correction of the majority of the transcriptional abnormalities
      in the brain (95.9%) and blood (97.7%), of which 182 and 290 transcripts were
      normalized in the brain and blood, respectively. These results demonstrate that a
      single systemic scAAVrh74-hSGSH delivery mediated efficient restoration of SGSH
      activity and resulted in a near complete correction of MPS IIIA molecular
      pathology. This study also demonstrates that blood transcriptional profiles
      reflect the biopathological status of MPS IIIA, and also respond well to
      effective treatments. 

PMID- 25592335
TI  - Controlled Striatal DOPA Production From a Gene Delivery System in a Rodent Model
      of Parkinson's Disease.
AB  - Conventional symptomatic treatment for Parkinson's disease (PD) with long-term L
      3,4-dihydroxyphenylalanine (DOPA) is complicated with development of drug-induced
      side effects. In vivo viral vector-mediated gene expression encoding tyrosine
      hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) provides a drug delivery
      strategy of DOPA with distinct advantages over pharmacotherapy. Since the brain
      alterations made with current gene transfer techniques are irreversible, the
      therapeutic approaches taken to the clinic should preferably be controllable to
      match the needs of each individual during the course of their disease. We used a
      recently described tunable gene expression system based on the use of
      destabilized dihydrofolate reductase (DD) and generated a N-terminally coupled
      GCH1 enzyme (DD-GCH1) while the TH enzyme was constitutively expressed, packaged
      in adeno-associated viral (AAV) vectors. Expression of DD-GCH1 was regulated by
      the activating ligand trimethoprim (TMP) that crosses the blood-brain barrier. We
      show that the resulting intervention provides a TMP-dose-dependent regulation of
      DOPA synthesis that is closely linked to the magnitude of functional effects. Our
      data constitutes the first proof of principle for controlled reconstitution of
      dopamine capacity in the brain and suggests that such next-generation gene
      therapy strategies are now mature for preclinical development toward use in
      patients with PD. 

PMID- 25592336
TI  - Targeted gene delivery to the enteric nervous system using AAV: a comparison
      across serotypes and capsid mutants.
AB  - Recombinant adeno-associated virus (AAV) vectors are one of the most widely used
      gene transfer systems in research and clinical trials. AAV can transduce a wide
      range of biological tissues, however to date, there has been no investigation on
      targeted AAV transduction of the enteric nervous system (ENS). Here, we examined
      the efficiency, tropism, spread, and immunogenicity of AAV transduction in the
      ENS. Rats received direct injections of various AAV serotypes expressing green
      fluorescent protein (GFP) into the descending colon. AAV serotypes tested
      included; AAV 1, 2, 5, 6, 8, or 9 and the AAV2 and AAV8 capsid mutants, AAV2
      Y444F, AAV2-tripleY-F, AAV2-tripleY-F+T-V, AAV8-Y733F, and AAV8-doubeY-F+T-V.
      Transduction, as determined by GFP-positive cells, occurred in neurons and
      enteric glia within the myenteric and submucosal plexuses of the ENS. AAV6 and
      AAV9 showed the highest levels of transduction within the ENS. Transduction
      efficiency scaled with titer and time, was translated to the murine ENS, and
      produced no vector-related immune response. A single injection of AAV into the
      colon covered an area of ~47 mm(2). AAV9 primarily transduced neurons, while AAV6
      transduced enteric glia and neurons. This is the first report on targeted AAV
      transduction of neurons and glia in the ENS. 

PMID- 25592337
TI  - Adenoassociated virus serotype 9-mediated gene therapy for x-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder
      caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding
      cassette transporter (ABCD1) responsible for transport of CoA-activated very long
      chain fatty acids (VLCFA) into the peroxisome for degradation. We used
      recombinant adenoassociated virus serotype 9 (rAAV9) vector for delivery of the
      human ABCD1 gene (ABCD1) to mouse central nervous system (CNS). In vitro,
      efficient delivery of ABCD1 gene was achieved in primary mixed brain glial cells
      from Abcd1-/- mice as well as X-ALD patient fibroblasts. Importantly, human ABCD1
      localized to the peroxisome, and AAV-ABCD1 transduction showed a dose-dependent
      effect in reducing VLCFA. In vivo, AAV9-ABCD1 was delivered to Abcd1-/- mouse CNS
      by either stereotactic intracerebroventricular (ICV) or intravenous (IV)
      injections. Astrocytes, microglia and neurons were the major target cell types
      following ICV injection, while IV injection also delivered to microvascular
      endothelial cells and oligodendrocytes. IV injection also yielded high
      transduction of the adrenal gland. Importantly, IV injection of AAV9-ABCD1
      reduced VLCFA in mouse brain and spinal cord. We conclude that AAV9-mediated
      ABCD1 gene transfer is able to reach target cells in the nervous system and
      adrenal gland as well as reduce VLCFA in culture and a mouse model of X-ALD. 

PMID- 25592338
TI  - Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the
      cellular membrane.
AB  - There has been a rapid emergence of numerous targeted agents in the oncology
      community in the last decade. This exciting paradigm shift in drug development
      lends promise for the future of individualized medicine. Given the pace of
      development and clinical deployment of targeted agents with novel mechanisms of
      action, dermatology providers may not be familiar with the full spectrum of
      associated skin-related toxicities. Cutaneous adverse effects are among the most
      frequently observed toxicities with many targeted agents, and their intensity can
      be dose-limiting or lead to therapy discontinuation. In light of the often life
      saving nature of emerging oncotherapeutics, it is critical that dermatologists
      both understand the mechanisms and recognize clinical signs and symptoms of such
      toxicities in order to provide effective clinical management. Part I of this
      continuing medical education article will review in detail the potential skin
      related adverse sequelae, the frequency of occurrence, and the implications
      associated with on- and off-target cutaneous toxicities of inhibitors acting at
      the cell membrane level, chiefly inhibitors of epidermal growth factor receptor,
      KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors. 

PMID- 25592339
TI  - Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of
      intracellular molecular signaling pathways.
AB  - The last decade has spawned an exciting new era of oncotherapy in dermatology,
      including the development of targeted therapies for metastatic melanoma and basal
      cell carcinoma. Along with skin cancer, deregulation of the PI3K-AKT-mTOR and RAS
      RAF-MEK-ERK intracellular signaling pathways contributes to tumorigenesis of a
      multitude of other cancers, and inhibitors of these pathways are being actively
      studied. Similar to other classes of targeted therapies, cutaneous adverse
      effects are among the most frequent toxicities observed with mitogen-activated
      protein kinase pathway inhibitors, PI3K-AKT-mTOR inhibitors, hedgehog signaling
      pathway inhibitors, and immunotherapies. Given the rapid expansion of these
      families of targeted treatments, dermatologists will be essential in offering
      dermatologic supportive care measures to cancer patients being treated with these
      agents. Part II of this continuing medical education article reviews skin-related
      adverse sequelae, including the frequency of occurrence and the implications
      associated with on- and off-target cutaneous toxicities of inhibitors of the RAS
      RAF-MEK-ERK pathway, PI3K-AKT-mTOR pathway, hedgehog signaling pathway, and
      immunotherapies.

PMID- 25592340
TI  - Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from
      Stevens-Johnson syndrome and erythema multiforme: a systematic review.
AB  - BACKGROUND: Mycoplasma pneumoniae infection is associated with extrapulmonary
      complications, including mucocutaneous eruptions. These eruptions, which have
      been termed either "Stevens-Johnson syndrome" or "erythema multiforme" in the
      literature, may differ from drug-induced Stevens-Johnson syndrome or viral
      associated erythema multiforme. OBJECTIVE: We sought to review the literature
      characterizing morphology and disease course of M pneumoniae-associated
      mucocutaneous disease. METHODS: A comprehensive literature search identified 95
      articles with 202 cases. RESULTS: Patients were often young (mean age: 11.9
      years) and male (66%). Cutaneous involvement ranged from absent (34%), to sparse
      (47%), to moderate (19%). Oral, ocular, and urogenital mucositis was reported in
      94%, 82%, and 63% of cases, respectively. Treatments included antibiotics (80%),
      systemic corticosteroids (35%), supportive care alone (8%), and/or intravenous
      immunoglobulin (8%). Complications included mucosal damage (10%), cutaneous
      scarring (5.6%), recurrence (8%), and mortality (3%). LIMITATIONS: Mild cases may
      not have been published; thus this review may have a bias toward more severe
      disease. CONCLUSION: M pneumoniae-associated mucocutaneous disease has prominent
      mucositis and sparse cutaneous involvement, although cutaneous involvement
      varies. Because of the distinct morphology, mild disease course, and potentially
      important clinical implications regarding treatment, we propose a revision of the
      nomenclature system and suggest the term "Mycoplasma-induced rash and mucositis"
      for these cases.

PMID- 25592341
TI  - Therapeutic management of DRESS: a retrospective study of 38 cases.
AB  - BACKGROUND: There is no consensus regarding treatment for drug reaction with
      eosinophilia and systemic symptoms (DRESS). OBJECTIVES: We report a single-center
      observational series of therapeutic management of DRESS. METHODS: We examined
      data for 50 consecutive patients admitted from March 2005 to June 2009 with a
      discharge diagnosis of DRESS (RegiSCAR score). RESULTS: For the 38 patients with
      a DRESS score of 4 or more, topical steroid treatment alone was initiated in 66%
      of cases. On admission, 13 patients received systemic steroids; in 7 of them,
      systemic steroid treatment was initiated or maintained for life-threatening organ
      failure, with kidney, lung, and/or nervous system involvement. Complications of
      DRESS, such as relapse, viral reactivation, and sepsis, were less frequent with
      topical steroid than with systemic steroids. None of the patients died during
      their stay in hospital. LIMITATIONS: Retrospective nonblinded design and
      dermatologic recruitment are limitations. The variables underlying the choice of
      treatment study were not analyzed. CONCLUSIONS: Systemic steroids may not be
      required for the management of mild forms of DRESS, and may thus be reserved for
      more severe cases. Prospective studies are required to evaluate strategies for
      treating DRESS.

PMID- 25592342
TI  - A high-tech ethical twist on the curbside consult.

PMID- 25592343
TI  - Allergen-specific IgE responses are found in pre-Sezary syndrome patients and in
      erythrodermic atopic patients but not in true Sezary syndrome patients.

PMID- 25592344
TI  - The dermatopathology requisition form: attitudes and practices of dermatologists.

PMID- 25592345
TI  - The use of oral pioglitazone in the treatment of lichen planopilaris.

PMID- 25592346
TI  - Trichoscopic features of frontal fibrosing alopecia: results in 249 patients.

PMID- 25592347
TI  - Treatment of alopecia areata with simvastatin/ezetimibe.

PMID- 25592348
TI  - Review of drug-related causes of oculocutaneous disease.

PMID- 25592349
TI  - Reply to: "Review of drug-related causes of oculocutaneous disease".

PMID- 25592350
TI  - Alitretinoin and Darier disease: "All that glisters is not gold".

PMID- 25592351
TI  - Laser-assisted drug delivery: enhanced response to ingenol mebutate after
      ablative fractional laser treatment.

PMID- 25592352
TI  - Reply to: "Laser assisted drug delivery: enhanced response to ingenol mebutate
      after ablative fractional laser treatment".

PMID- 25592353
TI  - Anal cancer screening.

PMID- 25592354
TI  - Response to: "Anal cancer screening".

PMID- 25592355
TI  - Reality in short-term international dermatology missions.

PMID- 25592356
TI  - Expanding the reality of short-term international volunteerism in dermatology.

PMID- 25592357
TI  - JAAD grand rounds. JAAD grand rounds quiz: a 64-year-old woman with an annular
      rash on the arm.
AB  - LEARNING OBJECTIVES: At the conclusion of this learning activity, physician
      participants should be able to assess their own diagnostic and patient management
      skills and use the results of this exercise to help determine personal learning
      needs. Instructions: In answering each question, refer to the specific directions
      provided. Because it is often necessary to provide information occurring later in
      a series that give away answers to earlier questions, please answer the questions
      in each series in sequence.

PMID- 25592359
TI  - JAAD grand rounds. Persistent and progressive purpura in a patient with an
      elevated rheumatoid factor and polyclonal gammopathy (hypergammaglobulinemic
      purpura of Waldenstrom).

PMID- 25592358
TI  - JAAD grand rounds. A patient with cardiovascular disease and widespread scaly
      plaques.

PMID- 25592363
TI  - Balloon cell nevus: histologic and dermoscopic features.

PMID- 25592364
TI  - Dermoscopic "signature" pattern of pigmented and nonpigmented facial actinic
      keratoses.

PMID- 25592365
TI  - The percutaneous set-back dermal suture.

PMID- 25592366
TI  - Use of cryobiopsy in dermatological practice.

PMID- 25592367
TI  - A novel point-of-care in vivo technique for preparation of epidermal cell
      suspension for transplantation in vitiligo.

PMID- 25592368
TI  - A cerebellar role in performance monitoring - evidence from EEG and voxel-based
      morphometry in patients with cerebellar degenerative disease.
AB  - The cerebellum applies an internal forward-model to predict the sensory
      consequences of actions. This forward-model is updated based on on-line
      performance monitoring. A previous study has shown that performance monitoring is
      altered in patients with focal vascular cerebellar lesions, but altered neural
      responses are not paralleled by impaired behaviour, and the critical cerebellar
      sites have yet to be identified. The present study investigated if saccadic
      performance monitoring is more severely altered in patients with cerebellar
      degenerative disease relative to the previously examined patients with focal
      vascular cerebellar lesions, and which cerebellar regions support performance
      monitoring. 16 patients and 16 healthy controls performed an antisaccade task
      while an electroencephalogram (EEG) was recorded. Error rates were increased, and
      the error-related negativity (ERN), an event-related potential (ERP) component
      associated with error processing/performance monitoring, was reduced while the
      error positivity (Pe), a later ERP component related to more conscious aspects of
      error processing, was preserved in patients. Thus, performance monitoring is
      altered in patients with cerebellar degeneration, confirming a critical role of
      the cerebellum for fast classification of saccadic accuracy. In contrast to
      patients with focal lesions, post-acute functional reorganization and
      compensation presumably is hampered by disease progression, resulting in altered
      neural processing and impaired behavioural performance. Voxel-based morphometry
      (VBM) indicated the strongest effects for behavioural performance, with
      correlations between gray matter volume reduction in bilateral posterolateral
      regions (left Crus II and right lobule VI) and increased error rates. Moreover,
      somewhat smaller correlations were found for volume loss in left lobule
      VIIb/VIIIa and right lobule V and ERN amplitude, and in right Crus I and Pe
      amplitude. The present findings are consistent with involvement of posterolateral
      cerebellar regions in motor and cognitive functions. 

PMID- 25592369
TI  - Abstract categories of functions in anterior parietal lobe.
AB  - Knowledge of function is critical for selecting objects to meet action goals,
      even when the affordances of those objects are not mechanical-for instance, both
      a painting and a vase can decorate a room. To identify neural representations of
      such abstract function concepts, we asked participants in an fMRI scanner to view
      a variety of objects and evaluate their utility to each of four goals (two
      Decoration goals: dress up for a night out and decorate a house, and two
      Protection goals: protect your body from the cold and keep objects dry in a
      flooded basement). These task conditions differed in the kind of functional
      evaluation participants had to perform over objects, but did not vary in the
      objects themselves. We performed a searchlight multivariate pattern analysis to
      identify cortical representations in which neural patterns were more similar for
      the pairs of similar-goal than dissimilar-goal task conditions (Decorate vs.
      Protect). We report such effects in anterior inferior parietal lobe (aIPL) close
      to regions typically reported for processing tool-related actions, and thought to
      be important for representing how they are manipulated. However, the current
      study design fully controlled for manipulation similarity, which predicted
      orthogonal relationships among the conditions. We conclude that the aIPL likely
      has nearby, but distinct, representations of both manipulation and function
      knowledge, and thereby may have a broader role in understanding how objects can
      be used, representing not just physical affordances but also abstract functional
      criteria such as esthetic value or purpose categories such as decorate. This
      pattern of localization has implications for how semantic knowledge is organized
      in the brain. 

PMID- 25592370
TI  - Suppressing a motivationally-triggered action tendency engages a response control
      mechanism that prevents future provocation.
AB  - Reward-predicting stimuli can induce maladaptive behavior by provoking action
      tendencies that conflict with long-term goals. Earlier, we showed that when human
      participants were permitted to respond for a reward in the presence of a task
      irrelevant, reward-predicting stimulus (i.e. goCS+ trials), the CS+ provoked an
      action tendency to respond compared to when a non-rewarding CS- stimulus was
      present (i.e. goCS- trials). However, when participants were not permitted to
      respond, response suppression was recruited to mitigate the action tendency that
      was triggered by the motivating CS+ stimulus (i.e. on nogoCS+ trials) (Freeman et
      al., 2014). Here we tested the hypothesis that repeated response suppression over
      a motivationally-triggered action tendency would reduce subsequent CS+
      provocation. We compared groups of participants who had different proportions of
      nogoCS+ trials, and we measured CS+ provocation on go trials via reaction time.
      Our results showed that CS+ provocation on go trials was reduced monotonically as
      the proportion of nogoCS+ trials increased. Further analysis showed that these
      group differences were best explained by reduced provocation on goCS+ trials that
      followed nogoCS+ (compared to nogoCS-) trials. Follow-up experiments using a
      neurophysiological index of motor activity replicated these effects and also
      suggested that, following nogoCS+ trials, a response suppression mechanism was in
      place to help prevent subsequent CS+ provocation. Thus, our results show that
      performing response suppression in the face of a motivating stimulus not only
      controls responding at that time, but also prevents provocation in the near
      future.

PMID- 25592371
TI  - (+)-Terrein inhibits human hepatoma Bel-7402 proliferation through cell cycle
      arrest.
AB  - Hepatoma is a common malignant tumor. Thus, the development of a high-efficacy
      therapeutic drug for hepatoma is required. In this study, (+)-terrein isolated
      from the marine sponge-derived Aspergillus terreus PF-26 against cell growth,
      apoptosis and cell cycle were assessed by MTT and flow cytometry. mRNA array
      containing 73 cell cycle-related genes and three cell morphology-related genes
      was generated and its performance evaluated. The cell cycle pathway map was
      created using the pathview package. The results showed that (+)-terrein inhibited
      the growth of Bel-7402 cells with alterations in cell morphology and a reduced
      transcript expression of cell morphology genes (fibronectin, N-cadherin, and
      vimentin). In addition, flow cytometric analysis revealed that (+)-terrein
      arrested the Bel-7402 cell cycle without inducing apoptosis. Based on multiple
      mRNA analysis, the downregulated expression of the CCND2, CCNE2, CDKN1C, CDKN2B,
      ANAPC, PKMYT1, CHEK2 and PCNA genes was observed in 10 uM (+)-terrein-treated Bel
      7402 cells (>2-fold and P<=0.05), compared with the controls. Thus, the
      antiprolife-rative mechanism of (+)-terrein against Bel-7402 cells may be due to
      the cell cycle arrest by blocking cell cycle gene expression and changing cell
      morphology.

PMID- 25592372
TI  - Thermal treatment of solid residues from WtE units: a review.
AB  - Thermal treatment methods of bottom ash, fly ash and various types of APC (air
      pollution control) residues from waste-to-energy plants can be used to obtain
      environmentally stable material. The thermal treatment processes are meant to
      reduce the leachability of harmful residue constituents, destroy toxic organic
      compounds, reduce residue volume, and produce material suitable for utilization.
      Fly ash and APC residues often have high levels of soluble salts, particularly
      chlorides, metals such as cadmium, lead, copper and zinc, and trace levels of
      organic pollutants such as dioxins and furans. Different thermal treatment
      methods can be used to either decompose or stabilize harmful elements and
      compounds in the ash, or separate them from the ash to get a material that can be
      safely stored or used as products or raw materials. In the present paper, thermal
      treatment methods, such as sintering, vitrification, and melting have been
      reviewed. In addition to a review of the scientific literature, a survey has been
      made of the extensive patent literature in the field. 

PMID- 25592373
TI  - Lactating performance, water and feed consumption of rabbit does reared under a
      Mediterranean summer circadian cycle of temperature v. comfort temperature
      conditions.
AB  - The general aim of this research was to study the effect of high ambient
      temperature on the performance of does during lactation, specifically the
      following factors: average daily feed (ADFI) and water (ADWI) intakes, daily milk
      yield (DMY); milk composition: dry matter (DM), CP and gross energy (GE); doe BW
      (DW); individual kit weaning weight (IWW) and litter survival rate during
      lactation (SR). The study was undertaken comparing the performance of two groups
      of contemporary does reared under the same management, feeding regime and
      environmental conditions, except the environmental temperature and humidity. A
      total of 80 females were randomly allocated, at 60 days of age, into two
      identical and continuous rooms. In one room, the temperature was maintained
      permanently within the thermo-neutral zone (between 18 degrees C to 22 degrees
      C); thus, environmental conditions in this room were considered as comfort
      conditions. In the second room, the environmental temperature pattern simulated
      the daily temperature cycles that were characteristic of the summer in
      Mediterranean countries (24 degrees C at 0800 h, increasing up to 29 degrees C
      until 1100 h; maintenance at 29 degrees C to 31 degrees C for 4 h and decreasing
      to about 24 degrees C to 26 degrees C around 1700 h until 0800 h of the following
      day), which were considered as thermal stress conditions. Females followed a semi
      intensive reproductive rhythm, first artificial insemination at 4.5 months of
      age, with subsequent 42-day reproductive cycles. Traits were recorded from a
      total of 138 lactations. Does were controlled up to the 5th lactation. Data were
      analyzed using linear and linear mixed models. High ambient temperature led to a
      lower ADFI (-9.4%), DW (-6.2%) and IWW (-8%), but it did not affect ADWI. No
      significant difference was found either for DMY, milk composition (DM, CP and GE)
      and SR during the lactation period. Heat stress was moderate, and does were able
      to adapt to it behaviorally by decreasing feed intake (to reduce heat
      production), but also live weight, allowing them to preserve milk yield and
      composition for assuring litter survival. On the other hand, water consumption
      could not be the main animal mechanism to overcome heat stress. 

PMID- 25592375
TI  - Scaling properties of information-theoretic quantities in density functional
      reactivity theory.
AB  - Density functional reactivity theory (DFRT) employs the electron density and its
      related quantities to describe reactivity properties of a molecular system.
      Quantities from information theory such as Shannon entropy, Fisher information,
      and Ghosh-Berkowitz-Parr entropy are natural descriptors within the DFRT
      framework. They have been previously employed to quantify electrophilicity,
      nucleophilicity and the steric effect. In this work, we examine their scaling
      properties with respect to the total number of electrons. To that end, we
      considered their representations in terms of both the electron density and the
      shape function for isolated atoms and neutral molecules. We also investigated
      their atomic behaviors in different molecules with three distinct partitioning
      schemes: Bader's zero-flux, Becke's fuzzy atom, and Hirshfeld's stockholder
      partitioning. Strong linear relationships of these quantities as a function of
      the total electron population are reported for atoms, molecules, and atoms in
      molecules. These relationships reveal how these information-theoretic quantities
      depend on the molecular environment and the electron population. These trends
      also indicate how these quantities can be used to explore chemical reactivity for
      real chemical processes. 

PMID- 25592374
TI  - Clinical significance of plasmacytoid dendritic cells and myeloid-derived
      suppressor cells in melanoma.
AB  - BACKGROUND: Immune markers in the peripheral blood of melanoma patients could
      provide prognostic information. However, there is currently no consensus on which
      circulating cell types have more clinical impact. We therefore evaluated myeloid
      derived suppressor cells (MDSC), dendritic cells (DC), cytotoxic T-cells and
      regulatory T-cells (Treg) in a series of blood samples of melanoma patients in
      different stages of disease. METHODS: Flow cytometry was performed on peripheral
      blood mononuclear cells of 69 stage I to IV melanoma patients with a median
      follow-up of 39 months after diagnosis to measure the percentage of monocytic
      MDSCs (mMDSCs), polymorphonuclear MDSCs (pmnMDSCs), myeloid DCs (mDCs),
      plasmacytoid DCs (pDCs), cytotoxic T-cells and Tregs. We also assessed the
      expression of PD-L1 and CTLA-4 in cytotoxic T-cells and Tregs respectively. The
      impact of cell frequencies on prognosis was tested with multivariate Cox
      regression modelling. RESULTS: Circulating pDC levels were decreased in patients
      with advanced (P = 0.001) or active (P = 0.002) disease. Low pDC levels conferred
      an independent negative impact on overall (P = 0.025) and progression-free
      survival (P = 0.036). Even before relapse, a decrease in pDC levels was observed
      (P = 0.002, correlation coefficient 0.898). High levels of circulating MDSCs
      (>4.13%) have an independent negative prognostic impact on OS (P = 0.012). MDSC
      levels were associated with decreased CD3+ (P < 0.001) and CD3 + CD8+ (P = 0.017)
      T-cell levels. Conversely, patients with high MDSC levels had more PD-L1+ T-cells
      (P = 0.033) and more CTLA-4 expression by Tregs (P = 0.003). pDCs and MDSCs were
      inversely correlated (P = 0.004). The impact of pDC levels on prognosis and
      prediction of the presence of systemic disease was stronger than that of MDSC
      levels. CONCLUSION: We demonstrated that circulating pDC and MDSC levels are
      inversely correlated but have an independent prognostic value in melanoma
      patients. These cell types represent a single immunologic system and should be
      evaluated together. Both are key players in the immunological climate in melanoma
      patients, as they are correlated with circulating cytotoxic and regulatory T
      cells. Circulating pDC and MDSC levels should be considered in future
      immunoprofiling efforts as they could impact disease management.

PMID- 25592376
TI  - Predictive factors for low rate of remission in a population of Colombian
      patients with severe proliferative lupus nephritis.
AB  - The objective of this study is to determine the predictive risk factors of
      failure to achieve remission within 12 months in a group of patients with
      proliferative lupus nephritis from Northwestern Colombia. Pragmatic clinical
      study with retrospective analysis was conducted. We included subjects with
      systemic lupus erythematosus as defined by the American College of Rheumatology
      with biopsy-proven nephritis. We assessed 149 patients, with 84 % female. Age at
      diagnosis of systemic lupus erythematosus is 24.7 years (16-31). The time between
      diagnosis of lupus erythematosus and proliferative nephritis is 2 months (0
      35.5). ISN/RPS 2003 histologic classification types are the following: IV (63.8
      %), III (13.4 %), V + III (3.3 %), and V + IV (3.3 %). Activity index is 6.18 +/-
      4.55 and chronicity index is 1 (0-3). The result of 24-h proteinuria is 2000 mg
      (667-4770) and baseline creatinine is 0.9 mg/dL (0.7-1.3). Induction therapy
      includes corticosteroids (100 %), cyclophosphamide (74.1 %), and mycophenolate
      mofetil (25.9 %). At 12 months, 40.7 % of individuals failed to attain partial or
      complete remission. Elevated creatinine (p = 0.0001) and 24-h proteinuria greater
      than 1500 mg (p = 0.0011) were basal predictors of failure to attain partial or
      complete remission by bivariate analysis. Similar results were obtained in
      multivariate analysis: Baseline creatinine elevation (OR 3.62, 95 % CI, 1.59
      8.23; p = 0.002) and 24-h proteinuria greater than 1500 mg (OR 3.62, 95 % CI,
      1.29-10.13; p = 0.014) were independent predictors of failure to achieve partial
      or complete remission. At 12 months, 40.7 % of patients did not attain partial or
      complete remission. Baseline elevated creatinine and 24-h proteinuria over 1500
      mg were predictors for poor response.

PMID- 25592377
TI  - NADPH oxidase 1-dependent ROS is crucial for TLR4 signaling to promote tumor
      metastasis of non-small cell lung cancer.
AB  - Recent evidence demonstrated an enhanced metastasis of non-small cell lung cancer
      (NSCLC) cells induced by lipopolysaccharide (LPS) stimulation, which reflected an
      important role of inflammation in tumor progression. However, the underlying
      mechanisms still remain unclear. Here, we evaluated the potential role of
      reactive oxygen species (ROS) in Toll-like receptor 4 (TLR4) signaling enhanced
      NSCLC metastasis. NSCLC cells were isolated from clinical surgical tissues. We
      found that LPS stimulation of NSCLC cells facilitates their metastasis that was
      accompanied by increased ROS production and could be abrogated by ROS inhibition.
      NADPH oxidase was essential for TLR4 signaling-enhanced NSCLC metastasis.
      Elevated NADPH oxidase 1 (NOX1) expression by LPS stimulation was observed.
      Blockade of NOX1 with ML171 alleviated enhanced NSCLC metastasis by TLR4
      signaling. Enforced NOX1 expression promoted TLR4 signaling-enhanced NSCLC
      metastasis, while decreased NOX1 expression inhibited TLR4 signaling-enhanced
      NSCLC metastasis. Further, NOX1 could regulate the expression of CXCR4 and matrix
      metallopeptidase 9 (MMP9) in NSCLC cells. NOX1 expression in tumor tissues was
      correlated with TLR4 expression and clinical stages in NSCLC patients. Finally,
      inhibition of NOX1/ROS prevented enhanced lung tumor burdens of NSCLC by LPS
      induced acute lung infection. Our findings demonstrated a crucial role of NOX1
      dependent ROS for TLR4 signaling to enhance the metastasis of NSCLC, which could
      further the understanding of NSCLC pathogenesis and helpful for developing novel
      therapeutics for NSCLC.

PMID- 25592378
TI  - SOX4 overexpression is a novel biomarker of malignant status and poor prognosis
      in breast cancer patients.
AB  - Sex-determining region Y-related high mobility group box 4 (SOX4) has been proven
      to serve as a critical role in cancer development and progression. However,
      little is known about the pathological role of SOX4 in breast cancer patients.
      The purpose of this study is to measure the expression of SOX4 in breast cancer
      patients and to explore the clinical significance of SOX4. Using RT-PCR and
      Western blot, messenger RNA (mRNA) and protein expression of SOX4 were measured
      in breast cancer tissues and adjacent normal mammary tissues. The relationship of
      SOX4 expression with clinical characteristics of 148 breast cancer patients was
      analyzed by immunohistochemistry. In the present study, our results indicated
      that SOX4 mRNA and protein were highly expressed in breast cancer tissues
      compared with adjacent normal mammary tissues and positively correlated with
      clinical stage (I-II vs. III-IV; P = 0.008), T classification (T1-T2 vs. T3-T4; P
      = 0.013), N classification (N0-N1 vs. N2-N3; P < 0.001), M classification (M0 vs.
      M1; P = 0.001), estrogen receptor (negative vs. positive; P = 0.029),
      progesterone receptor (negative vs. positive; P = 0.004), and histological grade
      (G1 vs. G2-G3; P = 0.033) in breast cancer patients. Furthermore, we also found
      that SOX4 protein overexpression was an unfavorable prognostic factor in breast
      cancer patients (P < 0.001), regardless of clinical stage, tumor size, lymph node
      metastasis, and distant metastasis. Finally, high SOX4 expression was an
      independent poor prognostic factor for pancreatic patients through multivariate
      analysis (P = 0.033). In conclusion, SOX4 overexpression serves as an unfavorable
      prognostic biomarker in breast cancer patients.

PMID- 25592379
TI  - Expression of Kindlin-1 in human hepatocellular carcinoma and its prognostic
      significance.
AB  - Kindlin-1 is a member of the Kindlin family of focal adhesion proteins and is
      implicated in cell adhesion, proliferation, polarity, and motility. Although
      expression of Kindlin-1 has recently been reported in a variety of human cancers,
      studies on its expression in human hepatocellular carcinoma (HCC) are currently
      lacking. This study aimed to determine the clinicopathological parameters and
      prognostic value of Kindlin-1 in HCC patients after surgical resection. The
      messenger RNA (mRNA) and protein levels of Kindlin-1 in 22 matched HCC specimens
      were assessed by quantitative real-time PCR (qRT-PCR) and Western blotting
      assays. The clinical and prognostic significance of Kindlin-1 in 68 cases of HCC
      was determined by immunohistochemistry. Kindlin-1 expression was higher in HCC
      tumor tissues relative to that in adjacent normal tissue at the both mRNA and
      protein levels (p < 0.05). Immunohistochemical results revealed that
      overexpression of Kindlin-1 was detected in 37 of 68 (54.4 %) tumor tissues and
      in seven of 68 (10.3 %) adjacent non-tumor tissues (p < 0.05). Positive Kindlin-1
      expression was significantly correlated with tumor size, tumor capsula, status of
      metastasis, and tumor-node-metastasis (TNM) stage. Additionally, Kaplan-Meier
      survival analysis showed that positive Kindlin-1 expression was associated with
      unfavorable overall survival (OS) and disease-free survival (DFS). Multivariate
      analysis identified Kindlin-1 as an independent prognostic predictor for OS and
      DFS in HCC patients (p = 0.041 and 0.027, respectively). Taken together, our data
      suggest that Kindlin-1 could play an important role in HCC and might serve as a
      promising prognostic marker and potential target for HCC therapy.

PMID- 25592380
TI  - MDC1 promotes ovarian cancer metastasis by inducing epithelial-mesenchymal
      transition.
AB  - Ovarian cancer is a highly invasive cancer with poor prognosis. Previous studies
      have revealed lots of connections between the invasiveness and epithelial
      mesenchymal transition (EMT), which is common during the progression of ovarian
      cancer. MDC1, a mediator of DNA damage checkpoint, has recently been implicated
      as a potential oncogene. Here, in this article, we studied the role of MDC1 in
      ovarian cancer metastasis. First, in tissue samples, we found that high
      expression level of MDC1 was correlated with poor prognosis. Furthermore, MDC1
      overexpression in ovarian cancer cells significantly increased migration and
      invasion. In contrast, silencing MDC1 reversed these processes. Consistently,
      nude mice xenograft confirmed that silencing MDC1 suppressed tumor metastasis in
      vivo. We further demonstrated that MDC1 induced EMT through modulation EMT
      markers such as E-cadherin, N-cadherin, and vimentin. Taken together, our
      findings suggest that MDC1 promotes ovarian cancer metastasis through the
      induction of EMT.

PMID- 25592382
TI  - [Nodular scleritis associated with pyoderma gangrenosum].

PMID- 25592381
TI  - Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase
      biology.
AB  - Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble
      inositol phosphates. Both sets of molecules represent versatile intracellular
      chemical signals in eukaryotes. While much effort has been invested in
      understanding the enzymes that produce and consume these molecules, central
      aspects for how phosphoinositide production is controlled and functionally
      partitioned remain unresolved and largely unappreciated. It is in this regard
      that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as
      central regulators of the functional channeling of phosphoinositide pools
      produced on demand for specific signaling purposes. The physiological
      significance of these proteins is amply demonstrated by the consequences that
      accompany deficits in individual PITPs. Although the biological problem is
      fascinating, and of direct relevance to disease, PITPs remain largely
      uncharacterized. Herein, we discuss our perspectives regarding what is known
      about how PITPs work as molecules, and highlight progress in our understanding of
      how PITPs are integrated into cellular physiology. This article is part of a
      Special Issue entitled Phosphoinositides. 

PMID- 25592384
TI  - Force irradiation effects during upper limb diagonal exercises on contralateral
      muscle activation.
AB  - The aim of this study was to explore the force irradiation effects of upper limb
      isometric diagonal exercises on shoulder muscle activities. Interactions among
      diagonal directions, contraction intensities (moderate and maximum) and sex were
      assessed. Thirty healthy subjects (11 males) performed isometric unilateral
      diagonal exercises based on proprioceptive neuromuscular facilitation technique
      in an isokinetic dynamometer with their dominant upper limbs. The second diagonal
      for flexion and for extension were assessed while the participants performed
      their maximum isometric torque (MIT) and at 25% of their MIT. During the exercise
      the muscle activity of the medial deltoid, pectoralis major and upper trapezius
      in the non-dominant (non-exercised) upper limbs of the participants was recorded
      by surface electromyography. The highest muscle activity occurred in the upper
      trapezius during the diagonal for flexion (27% of maximum isometric voluntary
      contractions). Upper trapezius and pectoralis major were more active during the
      diagonal for flexion than diagonal for extension (p < 0.001), while similar
      values between both diagonals were observed for the medial deltoid (p > 0.05). In
      conclusion, we observed that force irradiation during upper limb diagonal
      exercises is affected by diagonal direction, contraction intensity and sex when
      performed by healthy participants.

PMID- 25592383
TI  - [Efficacy of intravitreal dexamethasone implants in macular edema excluding
      venous occlusions: results for a cohort of 80 patients].
AB  - INTRODUCTION: The intravitreal dexamethasone implant has shown efficacy in the
      treatment of macular edema (ME) arising after retinal venous occlusions (central
      or branch), and in the treatment of non-infectious uveitis. The purpose of this
      study was to evaluate the efficacy of this implant in the treatment of other
      diffuse macular edemas with an inflammatory mechanism. MATERIALS AND METHODS: We
      carried out a retrospective cohort study over 2 years: from January 2012 to
      December 2013, including all patients who received at least one injection of
      intravitreal dexamethasone implant, excluding venous occlusions and non
      infectious uveitis. The primary study parameter was the progression of visual
      acuity. The study protocol had the approval of the institutional review board of
      the respective clinical ethics committees, and was conducted in accordance to the
      tenets of the Declaration of Helsinki. RESULTS: Eighty patients were included.
      Eighty-eight percent of patients were pseudophakic. The indications for treatment
      were: diabetic ME when anti-VEGF were ineffective (53%), ME after retinal
      detachment (RD) (22%), ME of Irvine-Gass syndrome (16%), ME after endophthalmitis
      (4%), macular telangiectasia (4%), ME secondary to retinitis pigmentosa (1%). The
      mean ETDRS visual acuity was 53.7 letters prior to injection, improving to 62.3
      letters after injection (P<0.001). The average gain in visual acuity was 6.7
      letters [4.53;8.84] (P<0.001) in patients treated for diabetic ME, 9.6 letters
      [6.1;13.1] (P<0.001) in patients with ME after RD, and 15.2 letters [10.25;20.28]
      (P<0.001) for Irvine-Gass syndrome. The mean duration of efficiency was 4.6
      months, with a median of 3.8 months. CONCLUSION: The intravitreal dexamethasone
      implant appears to be an effective second-line treatment even in patients with
      diabetic ME after failure or in the case of contraindication of anti-VEGF. It is
      also effective and well tolerated in patients with ME after RD, as well as in
      patients with Irvine-Gass syndrome.

PMID- 25592385
TI  - Longitudinal monitoring of the serotonin transporter gene expression to assess
      major depressive episode evolution.
AB  - BACKGROUND: Mood disorders are frequently characterized by uncertain prognosis
      and studying mRNA expression variations in blood cells represents a promising
      avenue of identifying biomarkers for mood disorders. State-dependent gene
      expression variations have been described during a major depressive episode
      (MDE), in particular for SLC6A4 mRNA, but how this transcript varies in relation
      to MDE evolution remains unclear. In this study, we prospectively assessed time
      trends of SCL6A4 mRNA expression in responder and nonresponder patients. METHODS:
      We examined SLC6A4 mRNA expression in blood samples from 13 patients treated for
      severe MDE and their matched controls by reverse transcription and quantitative
      PCR. All subjects were followed for 30 weeks. Patients were classified as either
      responders or nonresponders based on improvement of depression according to the
      17-item Hamilton Depression Rating Scale. Using a longitudinal design, we
      ascertained mRNA expression at baseline, 2, 8, and 30 weeks and compared mRNA
      expression between responder and nonresponder patients, and matched controls.
      RESULTS: We observed a decrease of SLC6A4 mRNA expression in responder patients
      across a 30-week follow-up, while nonresponder patients exhibited up-regulated
      SLC6A4 mRNA. CONCLUSION: Peripheral SLC6A4 mRNA expression could serve as a
      biomarker for monitoring and follow-up during an MDE and may help to more
      appropriately select individualized treatments.

PMID- 25592386
TI  - Cell penetrating peptides improve tumor delivery of cargos through neuropilin-1
      dependent extravasation.
AB  - Cell-penetrating peptides (CPPs), also referred to as protein transduction
      domains (PTDs), can mediate the cellular uptake of a wide range of macromolecules
      including peptides, proteins, oligonucleotides, and nanoparticles, and thus have
      received considerable attention as a promising method for drug delivery in vivo.
      Here, we report that CPP/PTDs facilitate the extravasation of fused proteins by
      binding to neuropilin-1 (NRP1), a vascular endothelial growth factor (VEGF) co
      receptor expressed on the surface of endothelial and some tumor cells. In this
      study, we examined the capacity of the amphipathic and cationic CPP/PTDs, PTD-3
      and TAT-PTD, respectively, to bind cells in vitro and accumulate in xenograft
      tumors in vivo. Notably, these functions were significantly suppressed by pre
      treatment with NRP1-neutralizing Ab. Furthermore, co-injection of iRGD, a cyclic
      peptide known to increase NRP1-dependent vascular permeability, significantly
      reduced CPP/PTD tumor delivery. This data demonstrates a mechanism by which NRP1
      promotes the extravasation of CPP/PTDs that may open new avenues for the
      development of more efficient CPP/PTD delivery systems. 

PMID- 25592388
TI  - Ban management consultants.

PMID- 25592389
TI  - Oncological impact of laparoscopic lymphadenectomy with preservation of the left
      colic artery for advanced sigmoid and rectosigmoid colon cancer.
AB  - BACKGROUND: Laparoscopic lymphadenectomy around the inferior mesenteric artery
      (IMA) with preservation of the left colic artery (LCA) remains a controversial
      approach. The aim of the study was to investigate the clinical outcomes. METHODS:
      This study analysed 211 patients who underwent laparoscopic resection of advanced
      (>=T3) sigmoid and rectosigmoid colon cancers with D3 lymphadenectomy including
      91 high ligations of the IMA (HL) and 120 low ligations with preservation of the
      LCA (LL) from January 1998 to December 2009. RESULTS: There were no significant
      differences in operative result between the groups. In stage II cancer, the
      overall survival rate (94.8% HL vs. 91.8% LL; 95% confidence interval (CI), -0.8
      to 0.68, p = 0.920) and disease-free survival (93.0% HL vs. 87.6% LL; 95% CI, 
      0.8 to 0.40, p = 0.540) did not differ significantly between the two groups. A
      similar tendency in overall survival was observed in patients with stage III
      cancer (88.3% HL vs. 86.9% LL; 95% CI, -0.44 to 0.57, p = 0.989) and disease-free
      survival (71.4% HL vs. 69.8% LL; 95% CI, -0.38 to 0.40, p = 0.637). CONCLUSIONS:
      Laparoscopic lymphadenectomy around the IMA with preservation of the LCA resulted
      in acceptable clinical outcomes in patients with advanced sigmoid and
      rectosigmoid colon cancer.

PMID- 25592390
TI  - Ethical euthanasia and short-term anesthesia of the chick embryo.
AB  - Fertilized chicken eggs are suggested as an alternative to mammalian models. The
      chorioallantoic membrane (CAM) of the chick embryo is widely used for examination
      of angiogenesis, xenotransplants and for virus production. Unfortunately, it is
      mostly not taken into account, that the chick embryo's ability to experience pain
      starts to develop at day 7 of breeding. In our view, this model is only in
      accordance with the 3 R principles, if an appropriate anesthesia of the chick
      embryo in potentially painful procedures is provided. Although many experimental
      approaches are performed on the none-innervated CAM, the euthanasia of the embryo
      strongly requires a more human technique than the usually used freezing at -20
      degrees C, decapitation or in ovo fixation with paraformaldehyde without prior
      anesthesia. However, protocols regarding feasible and ethical methods for
      anesthesia and euthanasia of avian embryos are currently not available.
      Therefore, we established an easy and reliable method for the euthanasia and
      short-term anesthesia of the chick embryo.

PMID- 25592387
TI  - MEN1, MEN4, and Carney Complex: Pathology and Molecular Genetics.
AB  - Pituitary adenomas are a common feature of a subset of endocrine neoplasia
      syndromes, which have otherwise highly variable disease manifestations. We
      provide here a review of the clinical features and human molecular genetics of
      multiple endocrine neoplasia (MEN) type 1 and 4 (MEN1 and MEN4, respectively) and
      Carney complex (CNC). MEN1, MEN4, and CNC are hereditary autosomal dominant
      syndromes that can present with pituitary adenomas. MEN1 is caused by
      inactivating mutations in the MEN1 gene, whose product menin is involved in
      multiple intracellular pathways contributing to transcriptional control and cell
      proliferation. MEN1 clinical features include primary hyperparathyroidism,
      pancreatic neuroendocrine tumours and prolactinomas as well as other pituitary
      adenomas. A subset of patients with pituitary adenomas and other MEN1 features
      have mutations in the CDKN1B gene; their disease has been called MEN4.
      Inactivating mutations in the type 1alpha regulatory subunit of protein kinase A
      (PKA; the PRKAR1A gene), that lead to dysregulation and activation of the PKA
      pathway, are the main genetic cause of CNC, which is clinically characterised by
      primary pigmented nodular adrenocortical disease, spotty skin pigmentation
      (lentigines), cardiac and other myxomas and acromegaly due to somatotropinomas or
      somatotrope hyperplasia. 

PMID- 25592391
TI  - Pathogen-expanded CD11b+ invariant NKT cells feedback inhibit T cell
      proliferation via membrane-bound TGF-beta1.
AB  - Natural killer T cells (NKT cells) are effector cells, but also regulator of
      immune response, which either promote or suppress immune response through
      production of different cytokines. However, the subsets of NKT cells with
      definite phenotype and regulatory function need to be further identified.
      Furthermore, the mechanisms for NKT cells to regulate immune response remain to
      be fully elucidated. Here we identified CD11b(+) invariant NKT (CD11b(+) iNKT)
      cells as a new subset of regulatory NKT cells in mouse models with infection.
      alphaGalCer:CD1d complex(+)TCRbeta(+)NK1.1(+) NKT cells could be categorized to
      CD11b(+) and CD11b(-) subsets. NKT cells are enriched in liver. During Listeria
      monocytogenes infection, hepatic CD11b(+) iNKT cells were significantly induced
      and expanded, with peak expansion on day 8. CD11b(+) iNKT cells were also
      expanded significantly in spleen and mesenteric lymph nodes. As compared to
      CD11b(-) iNKT cells, CD11b(+) iNKT cells expressed higher levels of CD27, FasL,
      B7H1, CD69, and particularly higher level of membrane-bound TGF-beta1 (mTGF
      beta1), but produced less IFN-gamma, IL-4, IL-10 and TGF-beta1. Hepatic CD11b(+)
      iNKT cells suppressed antigen-nonspecific and OVA-specific CD4 and CD8 T cell
      proliferation through mTGF-beta1 both in vitro and in vivo, meanwhile, they did
      not interfere with activation of CD4 T cells and cytotoxicity of the activated
      CD8 T cells. Thus, we have identified a new subset of pathogen-expanded CD11b(+)
      invariant NKT cells which can feedback inhibit T cell response through cell-to
      cell contact via cell surface (membrane-bound) TGF-beta1, especially at the late
      stage of immune response against infection. CD11b(+) regulatory iNKT cells may
      contribute to protect host from pathological injure by preventing immune
      overactivation.

PMID- 25592392
TI  - [GADV]-protein world hypothesis on the origin of life.
AB  - RNA world hypothesis is widely accepted still now, as an idea by which the origin
      of life might be explained. But, there are many weak points in the hypothesis. In
      contrast, I have proposed a more reasonable [GADV]-protein world hypothesis or
      GADV hypothesis, suggesting that life originated from the protein world, which
      was formed by pseudo-replication of [GADV]-proteins. In this communication, I
      will discuss about the origin of life from the point of view of the GADV
      hypothesis. 

PMID- 25592394
TI  - Novel repeated DNAs in the antarctic polyplacophoran Nuttallochiton mirandus
      (Thiele, 1906).
AB  - Within the scope of a project on the characterization of satellite DNAs in polar
      mollusks, the Antarctic chiton Nuttallochitonmirandus (Thiele, 1906) was
      analyzed. Two novel families of tandemly repeated DNAs, namely NmH and NmP, are
      described in their structure and chromosomal localization, and, furthermore,
      their presence was analyzed in related species. Data reported here display a
      particular variability in the structural organization of DNA satellites within
      this species. Processes driving satellite evolution, which are likely responsible
      for the intriguing variability of the identified satellite DNAs, are discussed.

PMID- 25592393
TI  - The phage growth limitation system in Streptomyces coelicolor A(3)2 is a
      toxin/antitoxin system, comprising enzymes with DNA methyltransferase, protein
      kinase and ATPase activity.
AB  - The phage growth limitation system of Streptomyces coelicolor A3(2) is an unusual
      bacteriophage defence mechanism. Progeny phiC31 phage from an initial infection
      are thought to be modified such that subsequent infections are attenuated in a
      Pgl(+) host but normal in a Pgl(-) strain. Earlier work identified four genes
      required for phage resistance by Pgl. Here we demonstrate that Pgl is an
      elaborate and novel phage restriction system that, in part, comprises a
      toxin/antitoxin system where PglX, a DNA methyltransferase is toxic in the
      absence of a functional PglZ. In addition, the ATPase activity of PglY and a
      protein kinase activity in PglW are shown to be essential for phage resistance by
      Pgl. We conclude that on infection of a Pgl(+) cell by bacteriophage phiC31, PglW
      transduces a signal, probably via phosphorylation, to other Pgl proteins
      resulting in the activation of the DNA methyltransferase, PglX and this leads to
      phage restriction.

PMID- 25592395
TI  - Bone Mineral Density, Anthropometric Indices, and the Prevalence of Osteoporosis
      in Northern (Beijing) Chinese and Southern (Hong Kong) Chinese Women--The Largest
      Comparative Study to Date.
AB  - This study was designed to compare the bone mineral density (BMD) and the
      prevalence of osteoporosis in community-dwelling women (aged 50-89) living in
      Northern (Beijing) and Southern (Hong Kong) China. Six thousand ninety-nine
      ambulatory Chinese women living in Hong Kong and 6302 mainland Chinese women
      living in Beijing were recruited for the study. The BMD was found to be 2.2%
      higher at the lumbar spine, 8.4% higher at the total hip, and 7.2% higher at the
      femoral neck in Beijing women than those in Hong Kong women. However, after
      adjustment for age, weight, and height, this trend was reversed so that the
      adjusted BMD at the lumbar spine, total hip, and femoral neck was 4.8%, 2.7%, and
      1.4% higher in Hong Kong Chinese women than Beijing Chinese women, respectively.
      Body weight accounted for 13.3%, 14.6%, and 10.6% of the difference in BMD of
      lumbar spine, total hip, and femoral neck between the 2 populations. The
      prevalence of osteoporosis in Hong Kong women (24.9%) was found to be higher than
      that in Beijing women (20.3%). We conclude that osteoporosis is a major health
      problem in Chinese women, and in comparing BMD between subjects of the same
      ethnicity, body weight must be taken into account. 

PMID- 25592396
TI  - Soccer increases bone mass in prepubescent boys during growth: a 3-yr
      longitudinal study.
AB  - The aim of this study was to examine the effect of 3-yr soccer practice on bone
      acquisition in prepubescent boys. We investigated 65 boys (aged 10-13 yr, Tanner
      stage I) at baseline, among which only 40 boys (Tanner stages II and III) have
      continued the 3-yr follow-up: 23 soccer players (F) completed 2-5 h of training
      plus 1 competition game per week and 17 controls (C). Bone mineral density (BMD,
      g/cm(2)) and bone mineral content (BMC, g) were measured by dual-energy X-ray
      absorptiometry at different sites. At baseline, BMD was higher in soccer players
      than in controls in the whole body and legs. In contrast, there was
      nonsignificant difference BMD in head, femoral neck, arms, and BMC in all
      measured sites between groups. At 3-yr follow-up, soccer players were found to
      have higher BMD and BMC at all sites than controls, except for head BMD and BMC
      and arms BMC in which the difference was nonsignificant between groups. During
      the 3-yr follow-up, the soccer players were found to gain significantly more in
      lumbar spine (31.2% +/- 2.9% vs 23.9% +/- 2.1%; p < 0.05), femoral neck (24.1% +/
      1.8% vs 11.4% +/- 1.9%; p < 0.001), whole body (16.5% +/- 1.4% vs 11.8% +/-
      1.5%; p < 0.05), and nondominant arm BMD (18.2% +/- 1.4% vs 13.6% +/- 1.7%; p <
      0.05) as well as lumbar spine (62.5% +/- 20.1% vs 39.5% +/- 20.1%; p < 0.001),
      femoral neck, (37.7% +/- 14.2% vs 28.9% +/- 12.8%; p < 0.05) and nondominant arm
      BMC (68.6% +/- 22.9% vs 50.1% +/- 22.4%; p < 0.05) than controls. In contrast,
      soccer players have less %BMD and %BMC changes in the head than controls. A
      nonsignificant difference was found in legs, dominant arm, head %BMD and %BMC
      changes, and whole-body %BMC changes between groups. In summary, we suggest that
      soccer has an osteogenic effect BMD and BMC in loaded sites in pubertal soccer
      players. The increased bone mass induced by soccer training in the stressed sites
      was associated to a decreased skull bone mass after 3 yr of follow-up.

PMID- 25592398
TI  - Conscientious objection and waiting time for voluntary abortion in Italy.
AB  - OBJECTIVES: This study sought to determine whether a correlation exists in Italy
      between conscience-based refusal by physicians to perform an abortion and waiting
      times for elective abortion. METHODS: Data on the number of objectors and of
      elective abortions performed within different time intervals were retrieved from
      annual Italian ministerial reports. Spearman's correlation coefficients were
      calculated between an indicator of the increase in workload for non-objectors
      when conscientious objection is exercised by physicians refusing to provide an
      abortion and the proportion of women whose request for an abortion was met within
      14 days, or later, in 13 regions in Italy. RESULTS: An inverse correlation
      emerged between the workload for non-objectors and the proportion of abortions
      performed within 14 days of the request in seven regions (statistically
      significant in Emilia-Romagna and Tuscany). There was a direct correlation
      between increased workload and the proportion of abortions performed later than
      21 days in nine regions. The same trends were highlighted at national level.
      CONCLUSIONS: Our results suggest that when data spanning at least more than a
      decade are available, a trend toward an inverse correlation can be noted between
      the workloads for non-objectors and timely access to elective abortion. This
      holds organisational and ethical implications.

PMID- 25592397
TI  - Prediction of muscle activity during loaded movements of the upper limb.
AB  - BACKGROUND: Accurate prediction of electromyographic (EMG) signals associated
      with a variety of motor behaviors could, in theory, serve as activity templates
      needed to evoke movements in paralyzed individuals using functional electrical
      stimulation. Such predictions should encompass complex multi-joint movements and
      include interactions with objects in the environment. METHODS: Here we tested the
      ability of different artificial neural networks (ANNs) to predict EMG activities
      of 12 arm muscles while human subjects made free movements of the arm or grasped
      and moved objects of different weights and dimensions. Inputs to the trained ANNs
      included hand position, hand orientation, and thumb grip force. RESULTS: The
      ability of ANNs to predict EMG was equally as good for tasks involving
      interactions with external loads as for unloaded movements. The ANN that yielded
      the best predictions was a feed-forward network consisting of a single hidden
      layer of 30 neural elements. For this network, the average coefficient of
      determination (R2 value) between predicted and actual EMG signals across all nine
      subjects and 12 muscles during movements that involved episodes of moving objects
      was 0.43. CONCLUSION: This reasonable accuracy suggests that ANNs could be used
      to provide an initial estimate of the complex patterns of muscle stimulation
      needed to produce a wide array of movements, including those involving object
      interaction, in paralyzed individuals.

PMID- 25592400
TI  - Brief Note: Response to Benatar.
AB  - In his response to my article entitled 'The Harm of Male-on-Female Rape: A
      Response to David Benatar', Benatar argues that I take his claims out of context,
      misrepresent them, and set up a straw man, which means, he claims, that I fail to
      respond to anything he has actually said. In this brief note, I respond to these
      allegations. 

PMID- 25592399
TI  - Safety and efficacy of sunitinib in patients from Italy with metastatic renal
      cell carcinoma: final results from an expanded-access trial.
AB  - OBJECTIVES: Patients with metastatic renal cell carcinoma (mRCC) received
      sunitinib in a global expanded-access program (EAP). Here, we report the efficacy
      and safety results for the EAP subpopulation in Italy. METHODS: Patients >=18
      years old with previously treated or treatment-naive mRCC received oral sunitinib
      50 mg/day on a 4-weeks-on/2-weeks-off schedule. Tumor measurements were scheduled
      per local practice (using Response Evaluation Criteria in Solid Tumors). Safety
      was regularly assessed. RESULTS: A total of 521 patients participated, including
      40% aged >=65 years, 11% with an Eastern Cooperative Oncology Group performance
      status >=2, 14% with non-clear cell RCC, and 11% with brain metastases. The
      median treatment duration and posttreatment follow-up were 7.4 and 12.3 months,
      respectively. The objective response rate was 12%, and the median progression
      free and overall survival was 9.1 and 27.2 months, respectively. 514 patients
      (99%) discontinued treatment; reasons included death (17%), nonresponse (46%), or
      adverse events (AEs; 13%). The most common any-grade treatment-related AEs were
      asthenia (44%, plus 15% reporting fatigue), thrombocytopenia and stomatitis (both
      37%), diarrhea (36%), mucosal inflammation (29%), hypertension (26%), and
      dysgeusia (25%). The most common grade 3/4 treatment-related AEs were
      thrombocytopenia (10%), asthenia (9%, plus 3% reporting fatigue), neutropenia,
      stomatitis (both 6%), and hypertension (5%). CONCLUSION: In a large population of
      Italian mRCC patients, sunitinib had a manageable safety profile and encouraging
      efficacy.

PMID- 25592401
TI  - A MALDI-Mass Spectrometry Imaging method applicable to different formalin-fixed
      paraffin-embedded human tissues.
AB  - Recent advancements in Matrix Assisted Laser Desorption/Ionisation (MALDI) Mass
      Spectrometry Imaging (MSI) technology have enabled the analysis of formalin-fixed
      paraffin-embedded (FFPE) tissue samples, unlocking a wealth of new proteomic
      information and facilitating the possibility of performing studies with higher
      statistical power as well as multi-centric collaborations within the field of
      proteomics research. However, current methods used to analyse these specimens are
      often time-consuming and they need to be modified when applied to human tissues
      of different origin. Here we present a reproducible and time-effective method
      that could address these aforementioned issues and widen the applicability of
      this technology to a number of challenging tissue types. Additionally, tissue
      molecular images show high spatial resolution and a strong correlation with the
      morphological features, enabling the identification of tissue morphology using
      statistically derived visualisation, without any prior knowledge. 

PMID- 25592403
TI  - Combined effects of cognitive bias for food cues and poor inhibitory control on
      unhealthy food intake.
AB  - The present study aimed to investigate the combined effects of cognitive bias
      (attentional and approach biases) and inhibitory control on unhealthy snack food
      intake. Cognitive biases reflect automatic processing, while inhibitory control
      is an important component of controlled processing. Participants were 146
      undergraduate women who completed a dot probe task to assess attentional bias and
      an approach-avoidance task to assess approach bias. Inhibitory control was
      measured with a food-specific go/no-go task. Unhealthy snack food intake was
      measured using a so-called "taste test". There was a significant interaction
      between approach bias and inhibitory control on unhealthy snack food intake.
      Specifically, participants who showed a strong approach bias combined with low
      inhibitory control consumed the most snack food. Theoretically, the results
      support contemporary dual-process models which propose that behaviour is guided
      by both automatic and controlled processing systems. At a practical level, the
      results offer potential scope for an intervention that combines re-training of
      both automatic and controlled processing. 

PMID- 25592402
TI  - Systemic arteriosclerosis and eating behavior in Japanese type 2 diabetic
      patients with visceral fat accumulation.
AB  - BACKGROUND: Visceral fat accumulation is a major etiological factor in the
      progression of type 2 diabetes mellitus and atherosclerosis. We described
      previously visceral fat accumulation and multiple cardiovascular risk factors in
      a considerable number of Japanese non-obese subjects (BMI <25 kg/m(2)). Here, we
      investigated differences in systemic arteriosclerosis, serum adiponectin
      concentration, and eating behavior in type 2 diabetic patients with and without
      visceral fat accumulation. METHODS: The study subjects were 75 Japanese type 2
      diabetes mellitus (age: 64.8 +/- 11.5 years, mean +/- SD). Visceral fat
      accumulation represented an estimated visceral fat area of 100 cm(2) using the
      bioelectrical impedance analysis method. Subjects were divided into two groups;
      with (n = 53) and without (n = 22) visceral fat accumulation. Systemic
      arteriosclerosis was scored for four arteries by ultrasonography. Eating behavior
      was assessed based on The Guideline for Obesity questionnaire issued by the Japan
      Society for the Study of Obesity. RESULTS: The visceral fat accumulation (+)
      group showed significantly higher systemic vascular scores and significantly
      lower serum adiponectin levels than the visceral fat accumulation (-) group. With
      respect to the eating behavior questionnaire items, (+) patients showed higher
      values for the total score and many of the major sub-scores than (-) patients.
      CONCLUSIONS: Type 2 diabetic patients with visceral fat accumulation showed 1)
      progression of systemic arteriosclerosis, 2) low serum adiponectin levels, and 3)
      differences in eating behavior, compared to those without visceral fat
      accumulation. Taken together, the findings highlight the importance of evaluating
      visceral fat area in type 2 diabetic patients. Furthermore, those with visceral
      fat accumulation might need to undergo more intensive screening for systemic
      arteriosclerosis and consider modifying their eating behaviors.

PMID- 25592404
TI  - Debate on evidence-based medicine.

PMID- 25592405
TI  - Measurement of gastric meal and secretion volumes using magnetic resonance
      imaging.
AB  - MRI can assess multiple gastric functions without ionizing radiation. However,
      time consuming image acquisition and analysis of gastric volume data, plus
      confounding of gastric emptying measurements by gastric secretions mixed with the
      test meal have limited its use to research centres. This study presents an MRI
      acquisition protocol and analysis algorithm suitable for the clinical measurement
      of gastric volume and secretion volume. Reproducibility of gastric volume
      measurements was assessed using data from 10 healthy volunteers following a
      liquid test meal with rapid MRI acquisition within one breath-hold and semi
      automated analysis. Dilution of the ingested meal with gastric secretion was
      estimated using a respiratory-triggered T1 mapping protocol. Accuracy of the
      secretion volume measurements was assessed using data from 24 healthy volunteers
      following a mixed (liquid/solid) test meal with MRI meal volumes compared to data
      acquired using gamma scintigraphy (GS) on the same subjects studied on a separate
      study day. The mean +/- SD coefficient of variance between 3 observers for both
      total gastric contents (including meal, secretions and air) and just the gastric
      contents (meal and secretion only) was 3  +/-  2% at large gastric volumes (>200
      ml). Mean +/- SD secretion volumes post meal ingestion were 64  +/-  51 ml and
      110  +/-  40 ml at 15 and 75 min, respectively. Comparison with GS meal volumes,
      showed that MRI meal only volume (after correction for secretion volume) were
      similar to GS, with a linear regression gradient +/- std err of 1.06  +/-  0.10
      and intercept -11  +/-  24 ml. In conclusion, (i) rapid volume acquisition and
      respiratory triggered T1 mapping removed the requirement to image during
      prolonged breath-holds (ii) semi-automatic analysis greatly reduced the time
      required to derive measurements and (iii) correction for secretion volumes
      provided accurate assessment of gastric meal volumes and emptying. Together these
      features provide the scientific basis of a protocol which would be suitable in
      clinical practice.

PMID- 25592406
TI  - Qianliening capsules influence the apoptosis of benign prostatic hyperplasia
      epithelial-1 cells by regulating the extracellular matrix.
AB  - The present study investigated whether Qianliening capsules (QC) affected the
      apoptosis of benign prostatic hyperplastia epithelial (BPH-1) cells by regulating
      the extracellular matrix (ECM). The levels of fibronectin (FN) and collagen IV
      were determined in the culture medium of BPH-1 cells maintained in normal medium
      and of BPH-1 cells maintained in an environment rich in FN and collagen IV using
      an enzyme-linked immunosorbent assay. Reverse transcription quantitative
      polymerase chain reaction and western blot analysis were performed to determine
      the mRNA and protein expression levels of FN, collagen IV, B-cell lymphoma 2 (Bcl
      2), Bcl-2-associated X protein (Bax) and cyclin D1, respectively. The cell
      morphology and viability were determined using light microscopy and an MTT assay
      and cell apoptosis was detected by annexin V staining. The results demonstrated
      that FN and collagen IV affected the apoptotic response of the BPH-1 cells, QC
      treatment significantly reduced the levels of FN and collagen IV secreted by the
      cells into the culture medium (P<0.01), inhibited the mRNA and protein expression
      levels of FN, collagen IV, Bcl-2 and cyclin D1 and promoted the mRNA and protein
      expression of Bax. Therefore, one of the mechanisms underlying the anti-BPH
      action of QC involves promoting apoptosis by regulating the expression of the
      extracellular matrix.

PMID- 25592407
TI  - GPs are told to treat with scepticism advice on anti-flu drugs from Public Health
      England.

PMID- 25592409
TI  - Discrepancies in assessment of adherence to antiplatelet treatment after
      myocardial infarction.
AB  - The poor response to clopidogrel is multifactorial and includes, amongst others,
      low patient adherence to medication. The aim of this study was to assess the
      reported patient adherence to treatment with clopidogrel and confront it with
      adherence assessed by drug availability. We evaluated determinants of adherence
      and its impact on platelet aggregation and clinical outcome. The study population
      comprised 184 patients treated with primary percutaneous coronary intervention
      for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9
      months after discharge. Patient adherence to clopidogrel was defined according to
      self-reported drug intake and verified based on data from the National Health
      Fund regarding the purchase of prescribed drugs. The patients were judged as
      adherent when the proportion of drug availability exceeded 80%. According to drug
      availability, 100 (54.3%) patients were adherent and 84 (45.7%) were nonadherent.
      The analysis identified the following factors as predictors of low adherence
      (<80%): adenosine diphosphate-induced platelet aggregation (ADP-PA) during
      hospitalization <=45 U, male gender and occurrence of ST-elevation myocardial
      infarction [(STEMI) vs. non-STEMI (NSTEMI)], while three-vessel disease was
      predictive of high adherence to medication. Compared with drug availability-based
      assessment, self-reported drug intake was significantly different: 172 (94.5%)
      patients reported regular and 10 (5.5%) patients reported irregular intake of
      clopidogrel. Clinical follow-up suggested that the self-reported nonregular
      clopidogrel intake may discriminate patients with a high risk of cardiovascular
      events. We demonstrated a huge discrepancy between the two most widely used
      methods for the evaluation of adherence to clopidogrel in secondary prevention
      treatment in patients after STEMI and NSTEMI. ADP-PA during hospitalization <=45
      U, male gender and STEMI (vs. NSTEMI) were independent predictors of nonadherence
      while three-vessel disease was independently predictive of adherence to treatment
      with clopidogrel in the investigated population.

PMID- 25592410
TI  - Lower serum levels of selenium, copper, and zinc are related to neuromotor
      impairments in children with konzo.
AB  - We assessed the relationship between key trace elements and neurocognitive and
      motor impairments observed in konzo, a motor neuron disease associated with
      cassava cyanogenic exposure in nutritionally challenged African children. Serum
      concentrations of iron, copper, zinc, selenium, and neurotoxic lead, mercury,
      manganese, cadmium, and cobalt were measured in 123 konzo children (mean age 8.53
      years) and 87 non-konzo children (mean age 9.07 years) using inductively coupled
      plasma mass spectrometry (ICPMS). Concentrations of trace elements were compared
      and related to performance scores on the Kaufman Assessment Battery for Children,
      2nd edition (KABC-II) for cognition and Bruininks-Oseretsky Test, 2nd edition
      (BOT-2) for motor proficiency. Children with konzo had low levels of selenium,
      copper, and zinc relative to controls. Selenium concentration significantly
      correlated with serum 8,12-iso-iPF2alpha-VI isoprostane (Spearman r=0.75, p<0.01)
      and BOT-2 scores (r=0.31, p=0.00) in children with konzo. Elemental deficiency
      was not associated with poor cognition. Mean (SD) urinary level of thiocyanate
      was 388.03 (221.75) MUmol/l in non-konzo compared to 518.59 (354.19) MUmol/l in
      konzo children (p<0.01). Motor deficits associated with konzo may possibly be
      driven by the combined effects of cyanide toxicity and Se deficiency on
      prooxidant mechanisms. Strategies to prevent konzo may include dietary
      supplementation with trace elements, preferentially, those with antioxidant and
      cyanide-scavenging properties.

PMID- 25592411
TI  - Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with
      brain iron accumulation.
AB  - BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) comprises a
      clinically and genetically heterogeneous group of diseases presenting with
      movement disorders and brain iron deposits. In addition to NBIA subtypes caused
      by mutations in PANK2 and PLA2G6, mutations in the C19orf12 gene were recently
      described as the third frequent cause of NBIA (called mitochondrial membrane
      protein-associated neurodegeneration, MPAN). Additionally, the X-linked gene
      WDR45 was found causative for a special subtype named static encephalopathy in
      childhood with neurodegeneration in adulthood (also called BPAN); however,
      analysis of this gene in a broader spectrum of NBIA has not been reported yet.
      METHODS: In a heterogeneous cohort of 69 patients with suspected NBIA that did
      not carry mutations in PANK2 and PLA2G6, the coding region of C19orf12 was
      evaluated by Sanger sequencing. The WDR45 gene was analyzed via high resolution
      melting and subsequent sequence analysis. RESULTS: Previously described
      homozygous C19orf12 mutations were found in 3/69 NBIA patients (4.3%). Analysis
      of the WDR45 gene revealed a novel heterozygous missense mutation in one female
      NBIA patient showing psychomotor retardation with secondary decline. CONCLUSIONS:
      C19orf12 mutations were confirmed in our heterogeneous NBIA cohort, while WDR45
      mutations appear to be restricted to the subtype showing encephalopathy in
      childhood with neurodegeneration in adulthood.

PMID- 25592412
TI  - An explorative study regarding the effect of l-deprenyl on cognitive and
      functional recovery in patients after stroke.
AB  - INTRODUCTION: Selegiline (l-deprenyl) is a selective monoamine oxidase type B
      inhibitor that has been shown to have neurotrophic and anti-apoptotic properties
      and to protect neurons in different experimental models of cerebral ischaemia.
      The aim of this explorative study was to investigate whether selegiline could
      enhance cognitive and functional recovery in stroke survivors. METHODS: This was
      a randomized controlled study in which patients enrolled within two weeks of
      stroke underwent a clinical and functional evaluation and a neuropsychological
      assessment. The patients were given selegiline (10mg/day) or matched placebo once
      a day for six weeks in addition to standard rehabilitation care. RESULTS: Of 137
      stroke survivors, 47 patients met the inclusion criteria and were randomly
      assigned to the Study Group (n=23) or the Control Group (n=24). The statistical
      analysis showed a significant improvement in most neuropsychological tests after
      two and six weeks in the study group; these improvements were not replicated in
      the control group. The between-group analysis revealed that the domains of
      attention and executive functions benefited most from the drug treatment. With
      regard to functional status, comparison of clinical scores at admission and
      discharge showed a statistically significant enhancement in both groups without
      statistically significant differences between the groups. CONCLUSIONS: These
      preliminary results suggest that selegiline administered in the subacute phase
      can promote cognitive functioning in stroke patients. Further studies will
      elucidate whether and how this enhancement can impact on functional recovery in
      the short and in the long term.

PMID- 25592413
TI  - Co-existence of tumefactive MS and hepatitis C: A need for further screening and
      new therapeutic challenge.

PMID- 25592414
TI  - Multifocal-motor-neuropathy-like disease associated with Infliximab treatment in
      a patient with Crohn's disease.
AB  - Multifocal motor neuropathy is an immune-mediated disorder characterized by motor
      conduction block in nerve-conduction studies. It is recognized that anti-TNF
      alpha therapies are associated with immune-mediated conditions as adverse events.
      We report a case of multifocal-motor-neuropathy-like disease associated with the
      use of Infliximab in a patient with Crohn's disease. The diagnosis was based on
      neurophysiological evaluation and complete screening tests. Clinical and
      laboratory findings were not compatible with other potential causes. There was a
      mild response to the IVIg treatment, and once Infliximab treatment was withdrawn,
      the patient made slow but substantial progress in his motor function, with
      partial improvement of motor conduction blocks in the last neurophysiological
      evaluation. We believe there is a causal relationship between anti-TNF-alpha
      treatment and the disorder in this patient. There are few well-documented reports
      of this association. To our knowledge, our case is the first occurring in a
      patient with Crohn's disease. 

PMID- 25592415
TI  - Ipsilesional limb ataxia and truncal ipsipulsion in isolated infarction of the
      superior cerebellar peduncle.
AB  - The clinical features of a lesion confined to the superior cerebellar peduncle
      (SCP) have not been defined well in human. A 92-year-old woman suddenly developed
      mild dysarthria and severe imbalance from an isolated unilateral SCP infarction,
      and examination showed ipsiversive ocular torsion, severe ipsilesional limb
      ataxia, and truncal ipsipulsion. These findings are well consistent with those
      observed in monkeys when the SCP was severed. In addition to the dentate-rubro
      thalamic projections, the SCP appears to contain the fibers involved in the
      control of eye motion in the roll plane. 

PMID- 25592416
TI  - Puerarin alleviates noise-induced hearing loss via affecting PKCgamma and GABAB
      receptor expression.
AB  - Noise-induced hearing loss (NIHL) often results from prolonged exposure to high
      levels of noise. Our previous study revealed that during the development of NIHL,
      the expression of protein kinase C gamma subunit (PKCgamma) and GABAB receptor
      (GABABR) was changed within the cochlear nuclear complex (CNC), suggesting that
      these molecules might be the potential targets for the treatment of NIHL. As an
      extending study, here we focused on puerarin, a major isoflavonoid extracted from
      Pueraria lobota, which has been used in the treatment of cardiovascular and
      cerebrovascular diseases, and investigated whether it could protect against NIHL
      by acting on PKCgamma and GABABR. Transgenic GAD67-GFP knock-in mice were
      subjected to the NIHL model and their auditory functions were evaluated by the
      auditory brainstem response thresholds and distortion product oto-acoustic
      emission signals. Our results showed that 200mg/kg puerarin treatment ameliorated
      the thresholds of auditory brainstem response of NIHL mice significantly. Triple
      immunofluorescence staining and electron microscopy results revealed that GFP
      positive neurons in the superficial layers of CNC expressed both PKCgamma and
      GABABR1, and GAD67-positive terminals contacted PKCgamma- or GABABR1-positive
      neurons. Immunoblotting and RT-PCR results showed that NIHL increased the
      expression of PKCgamma but decreased that of GABABR1 and GABABR2 at both protein
      and mRNA levels in the CNC. Puerarin significantly attenuated the increased
      expression of PKCgamma but elevated the reduced expression of GABABR1 and GABABR2
      after noise exposure. Thus, we provided the first evidence that puerarin
      ameliorated the auditory functions of NIHL mice, and this effect may be due to
      its ability to regulate the expression of PKCgamma and GABABR. 

PMID- 25592417
TI  - Rayleigh approximation to ground state of the Bose and Coulomb glasses.
AB  - Glasses are rigid systems in which competing interactions prevent simultaneous
      minimization of local energies. This leads to frustration and highly degenerate
      ground states the nature and properties of which are still far from being
      thoroughly understood. We report an analytical approach based on the method of
      functional equations that allows us to construct the Rayleigh approximation to
      the ground state of a two-dimensional (2D) random Coulomb system with logarithmic
      interactions. We realize a model for 2D Coulomb glass as a cylindrical type II
      superconductor containing randomly located columnar defects (CD) which trap
      superconducting vortices induced by applied magnetic field. Our findings break
      ground for analytical studies of glassy systems, marking an important step
      towards understanding their properties. 

PMID- 25592418
TI  - Sustainability. Planetary boundaries: guiding human development on a changing
      planet.
AB  - The planetary boundaries framework defines a safe operating space for humanity
      based on the intrinsic biophysical processes that regulate the stability of the
      Earth system. Here, we revise and update the planetary boundary framework, with a
      focus on the underpinning biophysical science, based on targeted input from
      expert research communities and on more general scientific advances over the past
      5 years. Several of the boundaries now have a two-tier approach, reflecting the
      importance of cross-scale interactions and the regional-level heterogeneity of
      the processes that underpin the boundaries. Two core boundaries-climate change
      and biosphere integrity-have been identified, each of which has the potential on
      its own to drive the Earth system into a new state should they be substantially
      and persistently transgressed.

PMID- 25592420
TI  - Exoplanet dynamics. Asynchronous rotation of Earth-mass planets in the habitable
      zone of lower-mass stars.
AB  - Planets in the habitable zone of lower-mass stars are often assumed to be in a
      state of tidally synchronized rotation, which would considerably affect their
      putative habitability. Although thermal tides cause Venus to rotate retrogradely,
      simple scaling arguments tend to attribute this peculiarity to the massive
      Venusian atmosphere. Using a global climate model, we show that even a relatively
      thin atmosphere can drive terrestrial planets' rotation away from synchronicity.
      We derive a more realistic atmospheric tide model that predicts four asynchronous
      equilibrium spin states, two being stable, when the amplitude of the thermal tide
      exceeds a threshold that is met for habitable Earth-like planets with a 1-bar
      atmosphere around stars more massive than ~0.5 to 0.7 solar mass. Thus, many
      recently discovered terrestrial planets could exhibit asynchronous spin-orbit
      rotation, even with a thin atmosphere. 

PMID- 25592419
TI  - Optical imaging. Expansion microscopy.
AB  - In optical microscopy, fine structural details are resolved by using refraction
      to magnify images of a specimen. We discovered that by synthesizing a swellable
      polymer network within a specimen, it can be physically expanded, resulting in
      physical magnification. By covalently anchoring specific labels located within
      the specimen directly to the polymer network, labels spaced closer than the
      optical diffraction limit can be isotropically separated and optically resolved,
      a process we call expansion microscopy (ExM). Thus, this process can be used to
      perform scalable superresolution microscopy with diffraction-limited microscopes.
      We demonstrate ExM with apparent ~70-nanometer lateral resolution in both
      cultured cells and brain tissue, performing three-color superresolution imaging
      of ~10(7) cubic micrometers of the mouse hippocampus with a conventional confocal
      microscope. 

PMID- 25592421
TI  - Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2
      relaxometry and diffusion tensor imaging at 7T.
AB  - The present study examines the change in water diffusion properties of the corpus
      callosum (CC) and the hippocampus, in response to prolonged hypobaric hypoxia
      (HH) stress, using in vivo magnetic resonance imaging (MRI) modalities such as T2
      relaxometry and diffusion tensor imaging (DTI). Three groups of rats (n=7/group)
      were exposed to a simulated altitude of 6700m above sea level for the duration of
      7, 14 and 21days, respectively. Data were acquired pre-exposure, post-exposure
      and after 1week of normoxic follow-up in each group. The increment in T2 values
      with no apparent diffusion coefficient (ADC) change in the CC after 7 and 14days
      of HH exposure indicated mixed (vasogenic and cytotoxic) edema formation. After
      1week of normoxia, 7-day HH-exposed rats showed a decrease in ADC values in the
      CC, probably due to cytotoxic edema. A delayed decrease in ADC values was
      observed in the hippocampus after 1week normoxic follow-up in 7- and 14-day HH
      groups giving an insight of cytotoxic edema formation. Interestingly, 21-day HH
      exposed rats did not show change in ADC values. The decrease in T2 values after
      14 and 21days in the hippocampal region depicts iron deposition, which was
      confirmed by histopathology. This study successfully demonstrated the use of MRI
      modality to trace water diffusion changes in the brain due to prolonged HH
      exposure. 

PMID- 25592422
TI  - Neural correlates of electrointestinography: insular activity modulated by
      signals recorded from the abdominal surface.
AB  - Although the neural correlates that underlie abdominal pain have been
      investigated, so-called brain processes involved in modulating "gut feelings"
      remain unclear. In the current study, we used electrointestinography (EIG) to
      measure intestinal activity of healthy humans at rest. EIG measured myoelectrical
      activity of intestinal smooth muscles from the abdominal surface and was
      simultaneously conducted along with brain activity measurement using functional
      magnetic resonance imaging (fMRI). Correlations between the frequency powers of
      EIG and fMRI signals during 30min of rest were then examined to elucidate gut
      brain interactions. Neural activity correlating with 0.14- to 0.21-Hz EIG
      (suggested to reflect intestinal activity) was observed in the right anterior and
      middle insula. Moreover, this EIG frequency band correlated with anxiety scores
      along with resting-state functional connectivity between the insula and dorsal
      anterior cingulate cortex. These findings suggest that the insular cortex could
      be the core region involved in central visceral processes associated with
      subjective feelings. 

PMID- 25592423
TI  - Characterization of nociceptive response to chemical, mechanical, and thermal
      stimuli in adolescent rats with neonatal dopamine depletion.
AB  - Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment
      during adulthood and the neonatal period exhibit akinetic motor activity and
      spontaneous motor hyperactivity during adolescence, respectively, indicating that
      the behavioral effects of dopamine depletion depend on the period of lesion
      development. Dopamine depletion during adulthood induces hyperalgesic response to
      mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal
      dopamine depletion on nociceptive response in adolescent rats are yet to be
      examined. The latter aspect was addressed in this study, and behavioral responses
      were examined using von-Frey, tail flick, and formalin tests. The formalin test
      revealed that rats with neonatal dopamine depletion exhibited a significant
      increase in nociceptive response during interphase (6-15min post formalin
      injection) and phase 2 (16-75min post formalin injection). This increase in
      nociceptive response to the formalin injection was not reversed by pretreatment
      with methamphetamine, which ameliorates motor hyperactivity observed in
      adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail
      flick tests failed to reveal significant differences in withdrawal thresholds
      between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal
      response to the formalin injection into the rat hind paw was also examined
      through immunohistochemical analysis of c-Fos protein. Significantly increased
      numbers of c-Fos-immunoreactive cells were observed in laminae I-II and V-VI of
      the ipsilateral spinal cord to the site of the formalin injection in rats with
      neonatal dopamine depletion compared with vehicle-treated rats. These results
      suggest that the dopaminergic neural system plays a crucial role in the
      development of a neural network for tonic pain, including the spinal neural
      circuit for nociceptive transmission, and that the mechanism underlying
      hyperalgesia to tonic pain is not always consistent with that of spontaneous
      motor hyperactivity induced by neonatal dopamine depletion. 

PMID- 25592424
TI  - Oxidative stress induced by cumene hydroperoxide evokes changes in neuronal
      excitability of rat motor cortex neurons.
AB  - Oxidative stress and the production of reactive oxygen radicals play a key role
      in neuronal cell damage. This paper describes an in vitro study that explores the
      neuronal responses to oxidative stress focusing on changes in neuronal
      excitability and functional membrane properties. This study was carried out in
      pyramidal cells of the motor cortex by applying whole-cell patch-clamp techniques
      on brain slices from young adult rats. Oxygen-derived free radical formation was
      induced by bath application of 10MUM cumene hydroperoxide (CH) for 30min. CH
      produced marked changes in the electrophysiological properties of neurons (n=30).
      Resting membrane potential became progressively depolarized, as well as
      depolarization voltage, with no variations in voltage threshold. Membrane
      resistance showed a biphasic behavior, increasing after 5min of drug exposure and
      then it started to decrease, even under control values, after 15 and 30min. At
      the same time, changes in membrane resistance produced compensatory variations in
      the rheobase. The amplitude of the action potentials diminished and the duration
      increased progressively over time. Some of the neurons under study also lost
      their ability to discharge action potentials in a repetitive way. Most of the
      neurons, however, kept their repetitive discharge even though their maximum
      frequency and gain decreased. Furthermore, cancelation of the repetitive firing
      discharge took place at intensities that decreased with time of exposure to CH,
      which resulted in a narrower working range. We can conclude that oxidative stress
      compromises both neuronal excitability and the capability of generating action
      potentials, and so this type of neuronal functional failure could precede the
      neuronal death characteristics of many neurodegenerative diseases. 

PMID- 25592425
TI  - Gender-specific brain regional variation of neurons, endogenous estrogen,
      neuroinflammation and glial cells during rotenone-induced mouse model of
      Parkinson's disease.
AB  - Rotenone (RT) produces reactive oxygen species (ROS) by inhibiting the
      mitochondrial electron transport chain; causing dopaminergic (DA) cell death in
      the substantia nigra (SN) and simulates other models of induced Parkinson's
      disease (PD). There is a sincere dearth of knowledge regarding the status of
      glial cells, neuroprotective estrogen and the status of neuroinflammatory TNF
      alpha in the different brain regions in either sex during healthy, as well as
      during PD conditions. In the present study of RT-induced mouse model of PD, we
      have selected the frontal cortex (FC), hippocampus (HC) and SN from either sex of
      Swiss albino mice as these are the major regions involved during PD pathogenesis.
      During non pathogenic conditions, the ROS-scavenging enzyme activity varied among
      the brain regions and also in between genders. The number of DOPA decarboxylase
      positive cells, astrocytes and microglia was similar in the respective regions of
      the brain in both the sexes. The level of proinflammatory cytokine TNF-alpha was
      same in the respective FC and HC in either sex except that of SN. The expression
      level of estrogen and its receptors varied among the three brain regions. During
      RT treatment, ROS-scavenging enzyme activities increased, DOPA decarboxylase
      positive neurons and fibers in DA as well as in norepinephrinergic (NE) systems
      become degenerated, number of astrocytes decreased and microglial cells increased
      in those specific brain regions in either of the sexes except in the SN region of
      males where astrocyte number remained unaltered and microglial cell percentage
      decreased. TNF-alpha increased in the FC and SN but remained unaltered in the HC
      of both sexes. Estradiol level decreased in the HC and SN but the level unevenly
      varied in the FC. Similarly, the estrogen bound and nuclear-cytosolic receptor
      alpha and beta also varied differentially among the brain regions of the two
      sexes. Therefore our present study depicts that there exists a clear variation of
      neuronal and astroglial cell population, estrogen and its receptor levels in
      different brain regions of both the sexes during control and RT-treated
      pathogenic condition and these variations have major implication in PD
      pathogenesis and progression. 

PMID- 25592426
TI  - Crucial role of astrocytes in temporal lobe epilepsy.
AB  - Astrocytes sense and respond to synaptic activity through activation of different
      neurotransmitter receptors and transporters. Astrocytes are also coupled by gap
      junctions, which allow these cells to redistribute through the glial network the
      K(+) ions excessively accumulated at sites of intense neuronal activity. Work
      over the past two decades has revealed important roles for astrocytes in brain
      physiology, and it is therefore not surprising that recent studies unveiled their
      involvement in the etiology of neurological disorders such as epilepsy.
      Investigation of specimens from patients with pharmacoresistant temporal lobe
      epilepsy and epilepsy models revealed alterations in expression, localization and
      function of astrocytic connexins, K(+) and water channels. In addition, disturbed
      gliotransmission as well as malfunction of glutamate transporters and of the
      astrocytic glutamate- and adenosine-converting enzymes - glutamine synthetase and
      adenosine kinase, respectively - have been observed in epileptic tissues.
      Accordingly, increasing evidence indicates that dysfunctional astrocytes are
      crucially involved in processes leading to epilepsy. These new insights might
      foster the search for new targets for the development of new, more efficient anti
      epileptogenic therapies. 

PMID- 25592427
TI  - Source localization of event-related brain activity elicited by food and nonfood
      odors.
AB  - Tastes and odors influence the perception of a meal. Especially food aromas can
      act as potent signals to modulate our eating behavior with strong dependency on
      the reward produced by food. In this investigation we aimed to study the
      electrophysiological response to food- and non-food-related odors in healthy
      volunteers. Analyses revealed specific scalp potential maps for the two
      conditions; in particular the source of the map in the "food" condition seemed to
      be associated with the processing of rewards; the specific map in the "non-food"
      condition reflects odor characteristics excluding the reward. 

PMID- 25592429
TI  - Ultra-slow frequency bands reflecting potential coherence between neocortical
      brain regions.
AB  - Recent studies of electromagnetic ultra-slow waves (?0.1Hz) have suggested that
      they play a role in the integration of otherwise disassociated brain regions
      supporting vital functions (Ackermann and Borbely, 1997; Picchioni et al., 2010;
      Knyazev, 2012; Le Bon et al., 2012). We emphasize this spectral domain in probing
      sensor coherence issues raised by these studies using Hilbert phase coherences in
      the human MEG. In addition, we ask: will temporal-spatial phase coherence in
      regional brain oscillations obtained from the ultraslow spectral bands of multi
      channel magnetoencephalograms (MEG) differentiate resting, "task-free" MEG
      records of normal control and schizophrenic subjects? The goal of the study is a
      comparison of the relative persistence of intra-regional phase locking values
      (PLVs), among 10, region-defined, sensors in examined in the resting
      multichannel, MEG records as a function of spectral frequency bands and
      diagnostic category. The following comparison of Hilbert-transform-engendered
      relative phases of each designated spectral band was made using their pair-wise
      PLVs. This indicated the proportion of shared cycle time in which the phase
      relations between the index location and reference leads were maintained. Leave
      one out, bootstrapping of the PLVs via a support vector machine (SVM), classified
      clinical status with 97.3% accuracy. It was generally the case that spectral
      bands ?1.0Hz generated the highest values of the PLVs and discriminated best
      between control and patient populations. We conclude that PLV analysis of the
      oscillatory patterns of MEG recordings in the ultraslow frequency bands suggest
      their functional significance in intra-regional signal coherence and provide a
      higher rate of classification of patients and normal subjects than the other
      spectral domains examined. 

PMID- 25592428
TI  - Teratogenic effects of pyridoxine on the spinal cord and dorsal root ganglia of
      embryonic chickens.
AB  - Our understanding of the role of somatosensory feedback in regulating motility
      during chicken embryogenesis and fetal development in general has been hampered
      by the lack of an approach to selectively alter specific sensory modalities. In
      adult mammals, pyridoxine overdose has been shown to cause a peripheral sensory
      neuropathy characterized by a loss of both muscle and cutaneous afferents, but
      predominated by a loss of proprioception. We have begun to explore the
      sensitivity of the nervous system in chicken embryos to the application of
      pyridoxine on embryonic days 7 and 8, after sensory neurons in the lumbosacral
      region become post-mitotic. Upon examination of the spinal cord, dorsal root
      ganglion and peripheral nerves, we find that pyridoxine causes a loss of
      neurotrophic tyrosine kinase receptor type 3-positive neurons, a decrease in the
      diameter of the muscle innervating nerve tibialis, and a reduction in the number
      of large diameter axons in this nerve. However, we found no change in the number
      of Substance P or calcitonin gene-related peptide-positive neurons, the number of
      motor neurons or the diameter or axonal composition of the femoral cutaneous
      nerve. Therefore, pyridoxine causes a peripheral sensory neuropathy in embryonic
      chickens largely consistent with its effects in adult mammals. However, the
      lesion may be more restricted to proprioception in the chicken embryo. Therefore,
      pyridoxine lesion induced during embryogenesis in the chicken embryo can be used
      to assess how the loss of sensation, largely proprioception, alters spontaneous
      embryonic motility and subsequent motor development. 

PMID- 25592430
TI  - Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+),K(+)
      ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant
      effect of chrysin.
AB  - Our working hypothesis is that brain neurotrophins and brain Na(+),K(+)-ATPase
      may be strongly associated with the occurrence of depression in animals subjected
      to chronic unpredictable mild stress (CUMS). Still, we believe that chrysin, a
      natural and bioactive flavonoid found in honey and some plants, can provide
      satisfactory effects on antidepressant therapy. Thus, we aimed to evaluate the
      effect of CUMS on brain-derived neurotropic factor (BDNF) and nerve growth factor
      (NGF) levels as well as the Na(+),K(+)-ATPase activity in the hippocampus and
      prefrontal cortex of female mice. We also aimed to examine the effect of a 28-day
      oral treatment with chrysin (5 or 20mg/kg) in female mice subjected to CUMS,
      comparing to the effect of fluoxetine. Results showed that CUMS applied for
      28days induced a decrease in BDNF and NGF levels as well as in the Na(+),K(+)
      ATPase activity. CUMS also promoted a depressive status in the swimming forced
      test (FST), in the sucrose preference test, and in corticosterone levels. Chrysin
      (20mg/kg) and fluoxetine also occasioned the up-regulation of BDNF and NGF levels
      in non-stressed mice and in mice subjected to CUMS. CUMS decreased non-protein
      thiol (NPSH) levels and increased reactive oxygen species (ROS) levels. In
      response to these changes, the glutathione reductase (GR), glutathione peroxidase
      (GPx) and catalase (CAT) activities were increased in mice exposed to CUMS.
      Chrysin and fluoxetine treatments protected against all these alterations,
      suggesting the involvement of the antioxidant function in the antidepressant
      effect of chrysin and fluoxetine. In conclusion, CUMS decreased BDNF and NGF
      levels as well as the Na(+),K(+)-ATPase activity in mice. Chrysin presented
      antidepressant effect in mice on behavioral, neurotrophic and biochemistry
      parameters equivalent to fluoxetine. Furthermore, we suggest that the up
      regulation of BDNF and NGF levels is a mechanism possibly involved in the
      antidepressant effect of chrysin in mice. 

PMID- 25592431
TI  - Type 2 diabetes reduces the proliferation and survival of oligodendrocyte
      progenitor cells in ishchemic white matter lesions.
AB  - Diabetes mellitus (DM) is a major risk factor for stroke and it exacerbates
      tissue damage after ischemic insult. Diabetes is one of the important causes of
      the progression of white matter lesion, however, the pathological mechanisms
      remain unclear. The present study evaluated the influences of type 2 DM on
      ischemic subcortical white matter injury and the recruitment of oligodendrocyte
      progenitor cells (OPCs) under chronic cerebral hypoperfusion using type 2
      diabetic (db/db) mice. After bilateral common carotid artery stenosis (BCAS), the
      rarefaction in the white matter was more severe in db/db mice than in db/+ mice,
      and the number of glutathione S-transferase-pi (GST-pi)-positive mature
      oligodendrocytes (OLG) was lower in db/db mice than in db/+ mice at 4 and 8 weeks
      after ischemia. There were no significant differences in the number of single
      stranded DNA (ssDNA)-positive apoptotic cells in the deep white matter between
      the db/db and db/+ mice. We found a transient increase in the platelet-derived
      growth factor receptor-alpha (PDGFRalpha)-positive OPCs in white matter lesions
      after ischemia. However, significantly fewer PDGFRalpha-positive OPCs were
      detected in db/db than db/+ mice from 4weeks after BCAS. The number of Ki67
      positive proliferating cells in the deep white matter was significantly lower in
      db/db mice than in db/+ mice from 4 to 8weeks after BCAS. Most of the Ki67
      positive cells were PDGFRalpha-positive OPCs. Finally, we assessed the survival
      of 5-bromo-2'-deoxyuridine (BrdU)-positive proliferating cells in ischemic white
      matter, and found significantly poorer survival of BrdU/PDGFRalpha-positive OPCs
      or BrdU/GST-pi-positive OLGs in the db/db mice compared to the db/+ mice in the
      white matter after BCAS. Our findings suggest that the type 2 DM mice exhibited
      more severe white matter injury 8 weeks after chronic ischemia. Decreased
      proliferation and survival of OPCs may play an important role in the progression
      of white matter lesions after ischemia in diabetics. 

PMID- 25592432
TI  - Seasonal variation in size estimates of Aedes albopictus population based on
      standard mark-release-recapture experiments in an urban area on Reunion Island.
AB  - The implementation of the sterile insect technique for area-wide vector control
      requires that natural population density be accurately estimated to determine
      both the appropriate time to treat and the adequate number of sterile males for
      release. Herein, we used mark-release-recapture (MRR) to derive seasonal
      abundance estimates of Aedes albopictus population sizes within a delimited
      geographical area in Reunion Island. Population size of Ae. albopictus was
      estimated through four mark-release-recapture experiments carried out separately
      in different seasons. Marked males and females were released each time, and
      recaptured using BG sentinel traps for six consecutive days. Data were used to
      estimate the population size using a conceptual model that incorporates the
      variation in daily mortality rates. The likely influence of environmental factors
      on the magnitude of catches and on population fluctuation was analyzed. A total
      of 2827 mosquitoes (1914 males and 913 females) were marked and released on four
      occasions during dry and wet seasons. After release, 138 males (7.21%) and 86
      females (9.41%) of the marked specimens were recaptured in subsequent samplings.
      The effectiveness of the daily captures of wild and released mosquitoes was
      significantly influenced by meteorological conditions such as temperature,
      rainfall, wind speed and light intensity. The estimates of Ae. albopictus
      population size obtained with our model estimator ranged from 298 to 1238 males
      and 604 to 2208 females per ha, with seasonal variability - higher population
      size in the humid season. The presented results will be essential in designing
      more effective sterile male release strategies for long-term suppression of wild
      Ae. albopictus populations. 

PMID- 25592433
TI  - Light Intensity Regulates LC-PUFA Incorporation into Lipids of Pavlova lutheri
      and the Final Desaturase and Elongase Activities Involved in Their Biosynthesis.
AB  - The microalga Pavlova lutheri is a candidate for the production of omega-3 long
      chain polyunsaturated fatty acid (LC-PUFA), due to its ability to accumulate both
      eicosapentaenoic (EPA) and docosahexaenoic acids. Outstanding questions need to
      be solved to understand the complexity of n-3 LC-PUFA synthesis and partitioning
      into lipids, especially its metabolic regulation, and which enzymes and/or
      abiotic factors control their biosynthesis. In this study, the radioactivity of
      14C-labeled arachidonic acid incorporated into the total lipids of P. lutheri
      grown under different light intensities and its conversion into labeled LC-PUFA
      were monitored. The results highlighted for the first time the light-dependent
      incorporation of LC-PUFA into lipids and the light-dependent activity of the
      final desaturation and elongation steps required to synthesize and accumulate n-3
      C20/C22 LC-PUFA. The incorporation of arachidonic acid into lipids under low
      light and the related Delta17-desaturation activity measured explain the
      variations in fatty acid profile of P. lutheri, especially the accumulation of n
      3 LC-PUFA such as EPA under low light conditions.

PMID- 25592434
TI  - High levan production by Bacillus licheniformis NS032 using ammonium chloride as
      the sole nitrogen source.
AB  - In this study, levan production by Bacillus licheniformis NS032 isolated from a
      petroleum sludge sample was investigated. High levan yield was obtained in a wide
      range of sucrose concentrations (up to 400 g/L) and, contrary to most levan
      producing strains, using ammonium chloride as the sole N source. Interaction
      between sucrose, ammonium chloride, and initial pH of the medium in a low sucrose
      (60-200 g/L) and a high sucrose (300-400 g/L) system was analyzed by response
      surface methodology. According to the calculated model in the low sucrose system,
      maximum predicted levan yield was 47.8 g/L (sucrose 196.8 g/L, ammonium chloride
      2.4 g/L, pH 7.0), while in the high sucrose system, levan yield was 99.2 g/L
      (sucrose 397.6 g/L, ammonium chloride 4.6 g/L, pH 7.4). In addition, protective
      effect of microbial levan against copper toxicity to Daphnia magna is observed
      for the first time. The acute toxicity (48 h EC50) of copper decreased from 0.14
      to 0.44 mg/L by levan in concentration of 50 ppm. 

PMID- 25592435
TI  - Epidemiological and clinical aspects will guide the neuroimaging research in
      bipolar disorder.
AB  - Although neurobiological mechanisms of bipolar disorder (BD) are still unclear,
      neural models of the disease have recently been conceptualised thanks to
      neuroimaging. Indeed, magnetic resonance imaging (MRI) studies investigating
      structural and functional connectivity between different areas of the brain
      suggest an altered prefrontal-limbic coupling leading to disrupted emotional
      processing in BD, including uncinate fasciculus, amygdala, parahippocampal
      cortex, cingulate cortex as well corpus callosum. Specifically, these models
      assume an altered prefrontal control over a hyperactivity of the subcortical
      limbic structures implicated in automatic emotional processing. This impaired
      mechanism may finally trigger emotional hyper-reactivity and mood episodes. In
      this review, we first summarised some key neuroimaging studies on BD. In the
      second part of the work, we focused on the heterogeneity of the available
      studies. This variability is partly due to methodological factors (i.e., small
      sample size) and differences among studies (i.e., MRI acquisition and post
      processing analyses) and partly to the clinical heterogeneity of BD. We finally
      outlined how epidemiological studies should indicate which risk factors and
      clinical dimensions of BD are relevant to be studied with neuroimaging in order
      to reduce heterogeneity and go beyond diagnostic categories. 

PMID- 25592436
TI  - Measuring anxiety in the elderly: psychometric properties of the state trait
      inventory of cognitive and somatic anxiety (STICSA) in an elderly Italian sample.
AB  - BACKGROUND: Despite its increasing personal and societal impact, assessment of
      late-life anxiety has received relatively little attention in psychiatric
      research. Differential symptom presentation and physical comorbidities among the
      elderly, relative to younger cohorts creates a need for anxiety measures that are
      psychometrically validated in the elderly. METHODS: The present study examined
      the factor structure and discriminant validity of the state-trait inventory for
      cognitive and somatic anxiety (STICSA) in a sample of Italian middle-aged and
      older adults. Participants were 396 community-dwelling middle-aged (50-64 years)
      and older (>=65 years) adults. In addition to the STICSA, participants completed
      two depression measures and a general well-being survey with physical and mental
      health subscales. RESULTS: Factor analysis supported the validity of both state
      trait and cognitive-somatic distinctions underlying the STICSA, all dimensions
      exhibited excellent internal consistency (Cronbach's alpha coefficients >= 0.86),
      and correlations with depression measures provided limited evidence for
      differentiation of anxious and depressive symptoms. The STICSA also showed
      evidence of discriminating anxious symptoms from physical health symptoms, a
      particularly relevant feature of a valid anxiety measure in elderly samples.
      CONCLUSIONS: The STICSA appears to be a valid measure of cognitive and somatic
      anxiety in the elderly.

PMID- 25592438
TI  - England continues to lag behind Europe in cancer survival, despite L 6.7 bn
      budget.

PMID- 25592437
TI  - Microarray-based characterization of differential gene expression during vocal
      fold wound healing in rats.
AB  - The vocal fold (VF) mucosa confers elegant biomechanical function for voice
      production but is susceptible to scar formation following injury. Current
      understanding of VF wound healing is hindered by a paucity of data and is
      therefore often generalized from research conducted in skin and other mucosal
      systems. Here, using a previously validated rat injury model, expression
      microarray technology and an empirical Bayes analysis approach, we generated a VF
      specific transcriptome dataset to better capture the system-level complexity of
      wound healing in this specialized tissue. We measured differential gene
      expression at 3, 14 and 60 days post-injury compared to experimentally naive
      controls, pursued functional enrichment analyses to refine and add greater
      biological definition to the previously proposed temporal phases of VF wound
      healing, and validated the expression and localization of a subset of previously
      unidentified repair- and regeneration-related genes at the protein level. Our
      microarray dataset is a resource for the wider research community and has the
      potential to stimulate new hypotheses and avenues of investigation, improve
      biological and mechanistic insight, and accelerate the identification of novel
      therapeutic targets. 

PMID- 25592439
TI  - Motor neurone disease presenting with raised serum Troponin T.
AB  - Myocardial damage indicated by a rise in cardiac Troponin may not necessarily be
      due to a cardiac event. Many diseases such as sepsis, pulmonary embolism, heart
      and renal failure can also be associated with an elevated cardiac Troponin level.
      This brief report discusses the rare event of a patient with motor neurone
      disease, where the possible diagnosis of acute myocardial infarction arose due to
      an elevated cardiac Troponin. A 69-year-old gentleman presented with a history of
      a central chest ache of mild intensity, lasting a total of 2 h prior to complete
      resolution. Multiple cardiac Troponin assays were elevated, and echocardiography
      did not show any acute changes of myocardial damage. His electrocardiogram was
      also normal. This patient's raised cardiac Troponin was therefore explained on
      the basis of his active motor neurone disease. This rare case outlines the
      importance of considering motor neurone disease as a cause of elevated cardiac
      Troponin in the absence of clinical evidence of an acute coronary event. 

PMID- 25592440
TI  - Exploring patterns of error in acute care using framework analysis.
AB  - BACKGROUND: Junior doctors are often the first responders to deteriorating
      patients in hospital. In the high-stakes and time-pressured context of acute
      care, the propensity for error is high. This study aimed to identify the main
      subject areas in which junior doctors' acute care errors occur, and cross
      reference the errors with Reason's Generic Error Modelling System (GEMS). GEMS
      categorises errors according to the underlying cognitive processes, and thus
      provides insight into the causative factors. The overall aim of this study was to
      identify patterns in junior doctors' acute care errors in order to enhance
      understanding and guide the development of educational strategies. METHODS: This
      observational study utilised simulated acute care scenarios involving junior
      doctors dealing with a range of emergencies. Scenarios and the subsequent
      debriefs were video-recorded. Framework analysis was used to categorise the
      errors according to eight inductively-developed key subject areas. Subsequently,
      a multi-dimensional analysis was performed which cross-referenced the key subject
      areas with an earlier categorisation of the same errors using GEMS. The numbers
      of errors in each category were used to identify patterns of error. RESULTS:
      Eight key subject areas were identified; hospital systems, prioritisation,
      treatment, ethical principles, procedural skills, communication, situation
      awareness and infection control. There was a predominance of rule-based mistakes
      in relation to the key subject areas of hospital systems, prioritisation,
      treatment and ethical principles. In contrast, procedural skills, communication
      and situation awareness were more closely associated with skill-based slips and
      lapses. Knowledge-based mistakes were less frequent but occurred in relation to
      hospital systems and procedural skills. CONCLUSIONS: In order to improve the
      management of acutely unwell patients by junior doctors, medical educators must
      understand the causes of common errors. Adequate knowledge alone does not ensure
      prompt and appropriate management and referral. The teaching of acute care skills
      may be enhanced by encouraging medical educators to consider the range of
      potential error types, and their relationships to particular tasks and subjects.
      Rule-based mistakes may be amenable to simulation-based training, whereas skill
      based slips and lapses may be reduced using strategies designed to raise
      awareness of the interplay between emotion, cognition and behaviour.

PMID- 25592441
TI  - Review of the role of dynamic 18F-NaF PET in diagnosing and distinguishing
      between septic and aseptic loosening in hip prosthesis.
AB  - Joint replacements may fail due to infection, dislocation, peri-prosthetic
      fracture and loosening. Between 0.4 and 4% of joint replacements are known to be
      complicated by infection and aseptic loosening 2-18%. Differentiating between
      infection and aseptic loosening has an important bearing on the ongoing strategy
      for antimicrobial therapy and surgical intervention, but distinguishing one from
      the other can be difficult and will often require a battery of clinical and
      biochemical tests including the use of varying radiological modalities to
      accurately identify whether problematic joints are infected or aseptically loose.
      Prompt diagnosis is important due to the development of a biofilm on the surface
      of the infected prosthesis, which makes treatment difficult. There is no
      consensus among experts on the ideal imaging technique nor the methodology for
      image interpretation, but there is an increasing trend to apply hybrid imaging in
      the investigation of painful joint prosthesis and recent attempts have been made
      using PET-CT to identify aseptic loosening and infection with (18)F
      fluorodeoxyglucose (FDG) and sodium fluoride (18)F-Na. The aim of this paper is
      to evaluate the role of (18)F-NaF sodium fluoride ((18)F-NaF) positron emission
      tomography (PET) in distinguishing between septic and aseptic failure in hip and
      knee replacements, in addition to evaluating the feasibility of using multi
      sequential (18)F-NaF PET-CT for the assessment of painful lower limb prostheses. 

PMID- 25592442
TI  - Footshock facilitates methamphetamine-induced conditioned suppression through HPA
      axis, not dopamine.
AB  - The present study examined whether footshock can enhance methamphetamine (MAMPH)
      induced conditioned suppression and whether this effect involves the dopamine
      (DA) reward system or hypothalamic-pituitary-adrenal (HPA) axis. We also examined
      whether the footshock-induced enhancements of MAMPH-induced conditioned
      suppression are attributable to MAMPH's rewarding or aversive properties. During
      the footshock phase, all female rats received 0.1mg/kg haloperidol (HAL) and its
      vehicle (2% tartaric acid solution), or low and high doses of dexamethasone (DEX;
      0.5 and 1.0mg/kg) and its vehicle before each footshock (1mA, 2s), or no
      footshock, in seven trials once per day. The control group did not receive any
      drugs or footshocks. All of the rats were then allowed 15min access to a 0.1%
      saccharin solution and then received 2mg/kg MAMPH in five trials once per day.
      Footshock exhibited an increase in MAMPH-induced taste suppression. The low- and
      high-dose DEX groups but not the HAL group exhibited a blocking effect of the
      footshock enhancements of MAMPH-induced taste suppression. The low- and high-dose
      DEX groups exhibited a significant decrease in corticosterone levels during the
      footshock treatment phase but not during the testing phase. Altogether, the HPA
      stress system and not the DA reward system, particularly D2 receptors, appear to
      mediate the footshock-induced enhancements of MAMPH-induced conditioned taste
      suppression, which may result from the aversive and not the rewarding properties
      of MAMPH. The present findings may provide some clinical implications for
      alternating aversively classical conditioning for psychiatric disorders. 

PMID- 25592443
TI  - Low-dose endothelial monocyte-activating polypeptide-II increases permeability of
      blood-tumor barrier via a PKC-zeta/PP2A-dependent signaling mechanism.
AB  - Our previous study demonstrated that low-dose endothelial monocyte-activating
      polypeptide-II (EMAP-II) induces blood-tumor barrier (BTB) opening via the
      RhoA/Rho kinase/protein kinase C (PKC)-alpha/beta signaling pathway and that PKC
      zeta is involved in this process via other mechanisms. In the present study,
      using an in vitro BTB model, we detected the exact signaling mechanisms by which
      PKC-zeta activation affects EMAP-II-induced BTB hyperpermeability. Our results
      showed that three types of serine/threonine (Ser/Thr) protein phosphatases (PPs),
      namely PP1, PP2A, and PP2B, were expressed by rat brain microvascular endothelial
      cells (RBMECs). There was an interaction between PKC-zeta and PP2A in RBMECs. In
      addition, EMAP-II induced a significant increase in both the expression and the
      activity of PP2A in RBMECs. Inhibition of PKC-zeta with PKC-zeta pseudosubstrate
      inhibitor (PKC-zeta-PI) completely blocked EMAP-II-induced PP2A activation.
      Conversely, inhibition of PP2A with okadaic acid (OA) had no effect on EMAP-II
      induced PKC-zeta activation. Like PKC-zeta-PI, OA partially prevented EMAP-II
      induced BTB hyperpermeability and occludin redistribution in RBMECs. Neither PKC
      zeta-PI nor OA affected EMAP-II-induced phosphorylation of myosin light chain and
      redistribution of actin cytoskeleton in RBMECs. Taken together, our present study
      demonstrated that low-dose EMAP-II increases BTB permeability by activating the
      PKC-zeta/PP2A signaling pathway, which consequently leads to the disruption of
      TJs and impairment of endothelial barrier function.

PMID- 25592444
TI  - Management and outcomes of acute ST-segment-elevation myocardial infarction at a
      tertiary-care hospital in Sri Lanka: an observational study.
AB  - BACKGROUND: Sri Lanka is a developing country with a high rate of cardiovascular
      mortality. It is still largely dependent on thrombolysis for primary management
      of acute myocardial infarction. The aim of this study was to present current data
      on the presentation, management, and outcomes of acute ST-segment-elevation
      myocardial infarction (STEMI) at a tertiary-care hospital in Sri Lanka. METHODS:
      Eighty-one patients with acute STEMI presenting to a teaching hospital in
      Peradeniya, Sri Lanka, were included in this observational study. RESULTS: Median
      interval between symptom onset and hospital presentation was 60 min (mean 212
      min). Thrombolysis was performed in 73% of patients. The most common single
      reason for not performing thrombolysis was delayed presentation. Median door-to
      needle time was 64 min (mean, 98 min). Only 16.9% of patients received
      thrombolysis within 30 min, and none underwent primary PCI. Over 98% of patients
      received aspirin, clopidogrel, and a statin on admission. Intravenous and oral
      beta blockers were rarely used. Follow-up data were available for 93.8% of
      patients at 1 year. One-year mortality rate was 12.3%. Coronary intervention was
      performed in only 7.3% of patients post infarction. CONCLUSION: Late presentation
      to hospital remains a critical factor in thrombolysis of STEMI patients in Sri
      Lanka. Thrombolysis was not performed within 30 min of admission in the majority
      of patients. First-contact physicians should receive further training on
      effective thrombolysis, and there is an urgent need to explore the ways in which
      PCI and post-infarction interventions can be incorporated into treatment
      protocols.

PMID- 25592445
TI  - Foetal thyroid dysfunction: treat the mother first!
AB  - A case is presented of foetal compensated hypothyroidism due to persisting low
      maternal serum FT4 at the beginning of pregnancy. Diagnosis was made by means of
      foetal ultrasound followed by foetal blood sampling because of atypical findings.
      Foetal thyroid hypertrophy resolved progressively as exogenous thyroxine was
      administered to the mother. This case highlights once again the importance of
      adequate thyroid function during pregnancy.

PMID- 25592446
TI  - Which is the best advanced MR imaging protocol for predicting recurrent
      metastatic brain tumor following gamma-knife radiosurgery: focused on perfusion
      method.
AB  - INTRODUCTION: High spatial resolution of dynamic contrast-enhanced (DCE) MR
      imaging allows characterization of heterogenous tumor microenvironment. Our
      purpose was to determine which is the best advanced MR imaging protocol, focused
      on additional MR perfusion method, for predicting recurrent metastatic brain
      tumor following gamma-knife radiosurgery (GKRS). METHODS: Seventy-two consecutive
      patients with post-GKRS metastatic brain tumor were enrolled. Two readers
      independently calculated the percentile histogram cutoffs for normalized cerebral
      blood volume (nCBV) from dynamic susceptibility contrast (DSC) imaging and
      initial area under the time signal-intensity curve (IAUC) from DCE imaging,
      respectively. Area under the receiver operating characteristic curve (AUC) and
      interreader agreement were assessed. RESULTS: For differentiating tumor
      recurrence from therapy effect, adding DCE imaging to diffusion-weighted imaging
      (DWI) significantly improved AUC from 0.79 to 0.95 for reader 1 and from 0.80 to
      0.96 for reader 2, respectively. There was no significant difference of AUC
      between the combination of DWI with DSC imaging and the combination of DWI with
      DCE imaging for both readers. With the combination of DWI and DCE imaging, the
      sensitivity and specificity were 86.7 and 88.1% for reader 1 and 90.0 and 85.7%
      for reader 2, respectively. The intraclass correlation coefficient (ICC) between
      readers was highest for calculation of the 90th percentile histogram cutoffs for
      IAUC (ICC, 0.87). CONCLUSION: Adding perfusion MR imaging to DWI significantly
      improves the prediction of recurrent metastatic tumor; however, the diagnostic
      performance is not affected by selection of either DSC or DCE MR perfusion
      method.

PMID- 25592448
TI  - Platelet-derived chemokines in atherosclerosis.
AB  - In atherosclerosis, activated platelets have been recently recognised not only to
      participate in thrombotic events but also to play an essential role in the
      development of atherosclerotic lesions. Upon their activation, platelets release
      several pro-inflammatory mediators including chemokines. Chemokines are key
      molecules in inflammation as they are able to recruit leukocytes, modulate their
      activation/differentiation and control their proliferation/apoptosis. In this
      review we will discuss recent findings regarding the specific roles of chemokines
      released by platelets on leukocytes and their effects on atherosclerosis. 

PMID- 25592447
TI  - Osseous intramedullary signal alteration and enhancement in Sturge-Weber
      syndrome: an early diagnostic clue.
AB  - INTRODUCTION: Sturge-Weber syndrome (SWS) is a sporadic phakomatosis with
      variable intracranial involvement. Port-wine stain, choroidal angioma, and
      leptomeningeal angiomatosis typify the full disease spectrum. Disease
      manifestations generally evolve toward cerebral hemiatrophy and compensatory
      hemicalvarial enlargement. However, recognizable imaging correlates may be
      lacking early on. We have observed SWS-related marrow signal changes to be
      prevalent in patients of all ages. The purpose of this study is to evaluate bone
      marrow abnormalities in patients with Sturge-Weber syndrome. METHODS: The MR
      imaging database at an academic children's hospital was queried for "Sturge
      Weber" to build a cohort for retrospective analysis. Two board-certified
      neuroradiologists reviewed MR exams for abnormalities of the bone marrow, globes,
      susceptibility, and perfusion. A two-tailed Fisher's exact test was applied to
      evaluate the association between variables. RESULTS: Twenty brain MR exams from
      19 SWS patients, mean age 4.8 +/- 5.8 years (range 6 months-16 years), met the
      inclusion criteria. All patients with port-wine stains (18/20) had leptomeningeal
      enhancement, marrow T2 prolongation, and/or marrow enhancement ipsilaterally.
      Leptomeningeal enhancement was only present in 53%. Eighty percent had unilateral
      bone marrow abnormalities. In 37% (all <5 years), marrow abnormalities occurred
      without leptomeningeal angiomatosis. Thirty-five percent had facial bones
      involvement; 75% of these had ipsilateral choroidal angiomas. CONCLUSION: Bone
      marrow signal abnormality and enhancement is common ipsilateral to the nevus
      flammeus in SWS. As this may be the sole brain MR abnormality in some patients,
      it may reflect mild phenotypes or an early disease manifestation, and could help
      stratify patients for early intervention.

PMID- 25592449
TI  - Differences in participation rates and lessons learned about recruitment of
      participants--the European Health Examination Survey Pilot Project.
AB  - AIMS: In the 1980s, participation rates in health interview and health
      examination surveys were around 80% while now they are around 50-60%. There is
      also evidence that non-participation is selective. Low participation rates and
      selective non-participation may cause bias to our survey results based on
      participants alone. We aim to increase knowledge on cultural differences in
      acceptance and feasibility of different recruitment methods. METHODS: The
      European Health Examination Survey Pilot Project, conducted in 2009-2012,
      included pilot surveys in 12 countries among people aged 25-64 years. Information
      about recruitment methods and participation rates in these surveys was collected.
      RESULTS: Participation rates ranged from 16% to 57% for men and from 31% to 74%
      for women, where in most surveys women had higher participation rates than men. A
      variety of recruitment and promotion methods were used to obtain as high
      participation rates as possible. Combinations of phone calls, invitation letter
      and home visits were used to recruit invitees. Obtaining valid phone numbers for
      survey invitees was difficult in several countries. Incentives, websites and
      promotion in local media were used to promote the surveys. CONCLUSIONS: The
      European Health Examination Survey Pilot surveys showed that obtaining a
      participation rate above 50% for a representative population sample is possible
      but it requires hard work and a well-planned recruitment strategy. Recruitment
      methods used in one country may not be possible to use in another country due to
      cultural norms and national regulations.

PMID- 25592451
TI  - Apolipoprotein AI and HDL are reduced in stable cirrhotic patients with adrenal
      insufficiency: a possible role in glucocorticoid deficiency.
AB  - BACKGROUNDS AND AIMS: Adrenal insufficiency (AI) has been reported in patients
      with stable cirrhosis. A lack of substrates has been suggested as a possible
      contributing pathogenic mechanism leading to glucocorticoid deficiency in these
      subjects. To better explore this hypothesis, we studied lipoproteins in
      cirrhotics with and without AI. METHODS: A total of 81 cirrhotic patients and 30
      normal volunteers were enrolled. The severity of liver disease was graded by
      Child-Pugh score. Total cholesterol (TC), high-density lipoprotein (HDL), low
      density lipoprotein (LDL), triglyceride (TG), and apolipoprotein AI (Apo-AI)
      levels were evaluated. HDL subfractions were measured by gradient gel
      electrophoresis. Adrenal function was assessed by the Low-Dose Short Synacthen
      Test. RESULTS: Cirrhotic patients showed a significant reduction of TC, HDL, LDL,
      TG, and Apo-AI levels compared with controls. HDL3 was significantly lower, while
      HDL2 was higher, in cirrhotics compared with the controls. AI was observed in 26
      patients. TC, TG, HDL, and Apo-AI were significantly reduced in cirrhotics with
      AI compared with those with normal adrenal function. HDL2 and HDL3 did not differ
      between these two groups. Delta cortisol was related to TC (r = 0.30, p < 0.01),
      TG (r = 0.22, p = 0.05), and Apo-AI (r = 0.37, p < 0.001). Multivariate analysis
      revealed that Apo-AI and HDL were independently associated with AI. CONCLUSION:
      Our study shows that TC, TG, HDL, and Apo-AI are reduced in cirrhotics with AI.
      In particular, because both HDL and Apo-AI play a primary role in providing
      substrates for steroidogenesis to adrenal cells, this deficiency may contribute
      to the pathogenesis of AI in these patients.

PMID- 25592452
TI  - Evaluation considerations for community-based gender-informed health
      interventions.
AB  - Evaluations of gender-based interventions have been consistently criticized for
      their lack of methodological rigor. This is largely due to the complex design of
      many of the interventions, coupled with difficulties in measuring the outcome and
      impact of these interventions. This article proposes a number of ways to improve
      these evaluations both at the community and individual level. We recommend use of
      organizational theory and narrative inquiry methods, such as the appreciative
      inquiry technique, to examine how communities design gender-based interventions.
      In addition, we suggest a variety of methods to measure the effects of these
      interventions on gender norms in the community for example, policy analysis,
      multilevel modeling, and social conversations. With respect to measuring outcomes
      at the individual level, we argue for more rigorous evaluation designs in order
      to improve internal and external validity claims. Additionally, we suggest that
      evaluations should incorporate different methodologies, for example
      autobiographical narratives, which allows one to give saliency to the subjective
      voices of participants. Finally, we emphasize that evaluation designs need to
      document the long term effects of intervention programs and define the expected
      outcomes with greater specificity. 

PMID- 25592450
TI  - Overcoming tumor immune evasion with an unique arbovirus.
AB  - Combining dendritic cell vaccination with the adjuvant effect of a strain of
      dengue virus may be a way to overcome known tumor immune evasion mechanisms.
      Dengue is unique among viruses as primary infections carry lower mortality than
      the common cold, but secondary infections carry significant risk of hypovolemic
      shock. While current immuno-therapies rely on a single axis of attack, this
      approach combines physiological (hyperthermic reduction of tumor perfusion),
      immunological (activation of effector cells of the adaptive and innate immune
      system), and apoptosis-inducing pathways (sTRAIL) to destroy tumor cells. The
      premise of using multiple mechanisms of action in synergy with a decline in the
      ability of the tumor cells to employ resistance methods suggests the potential of
      this combination approach in cancer immunotherapy. 

PMID- 25592453
TI  - Effect of chronic cabergoline treatment and testosterone replacement on
      metabolism in male patients with prolactinomas.
AB  - INTRODUCTION: Hyperprolactinemia and hypogonadism are reportedly associated with
      an impaired metabolic profile. The current study aimed at investigating the
      effects of testosterone replacement and cabergoline (CAB) treatment on the
      metabolic profile in male hyperprolactinemic patients. PATIENTS AND METHODS:
      Thirty-two men with prolactinomas, including 22 with total testosterone (TT) <8
      nmol/l (HG, 69%) and 10 with TT >8 nmol/l (non-HG, 31%), were entered in the
      study. In all patients, metabolic parameters were assessed at diagnosis and after
      12- and 24-month treatment. RESULTS: Compared to non-HG patients, at baseline the
      HG patients had higher waist circumference (WC). TT significantly correlated with
      body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG
      prevalence significantly decreased (28%) and non-HG prevalence significantly
      increased (72%). Anthropometric and lipid parameters, fasting insulin (FI),
      insulin sensitivity index (ISI0), homeostatic model assessment of insulin
      secretion (HOMA-beta) and homeostatic model assessment of insulin resistance
      (HOMA-IR) significantly improved compared to baseline. TT was the best predictor
      for FI. Percent change (Delta) of TT significantly correlated with
      DeltaCholesterol, DeltaWeight and DeltaBMI. Compared to non-HG patients, the HG
      patients had a higher weight, BMI, WC and HOMA-beta. In HG, testosterone
      replacement was started. After 24 months, PRL normalized in 97%. HG prevalence
      significantly decreased (6%) and non-HG prevalence significantly increased (94%).
      Anthropometric and lipid parameters, FI, ISI0, HOMA-beta and HOMA-IR
      significantly improved compared to baseline, with FI, ISI0, HOMA-beta and HOMA-IR
      further ameliorating compared to the 12-month evaluation. Compared to non-HG
      patients, the HG patients still had a higher weight, BMI and WC. CONCLUSIONS: In
      hyperprolactinemic hypogonal men, proper testosterone replacement induces a
      significant improvement in the metabolic profile, even though the amelioration in
      the lipid profile might reflect the direct action of CAB.

PMID- 25592455
TI  - Ultrasound of the pleurae and lungs.
AB  - The value of ultrasound techniques in examination of the pleurae and lungs has
      been underestimated over recent decades. One explanation for this is the
      assumption that the ventilated lungs and the bones of the rib cage constitute
      impermeable obstacles to ultrasound. However, a variety of pathologies of the
      chest wall, pleurae and lungs result in altered tissue composition, providing
      substantially increased access and visibility for ultrasound examination. It is a
      great benefit that the pleurae and lungs can be non-invasively imaged repeatedly
      without discomfort or radiation exposure for the patient. Ultrasound is thus
      particularly valuable in follow-up of disease, differential diagnosis and
      detection of complications. Diagnostic and therapeutic interventions in patients
      with pathologic pleural and pulmonary findings can tolerably be performed under
      real-time ultrasound guidance. In this article, an updated overview is given
      presenting not only the benefits and indications, but also the limitations of
      pleural and pulmonary ultrasound. 

PMID- 25592454
TI  - Explaining the effects of electronic cigarettes on craving for tobacco in recent
      quitters.
AB  - OBJECTIVE: To explore how e-cigarettes attenuate craving for tobacco, in e
      cigarette users who recently quit smoking. DESIGN: Cross-sectional survey of
      recent quitters, Internet (French and English), 2012-2014. Participants were 374
      daily users of e-cigarettes who had quit smoking in the previous two months,
      enrolled on websites dedicated to e-cigarettes and to smoking cessation. We
      measured perception that e-cigarettes attenuate craving for tobacco cigarettes,
      characteristics of e-cigarettes, modifications of the devices, patterns of e
      cigarette use, reasons for use, satisfaction with e-cigarettes, dependence on e
      cigarettes, and personal characteristics. RESULTS: The strongest attenuation of
      craving for tobacco was obtained by using higher nicotine concentrations in
      refill liquids, modular systems (rather than unmodified devices), and high
      voltage batteries. The strength of the effect of e-cigarettes on craving was also
      associated with more intensive use (more puffs per day, more refill liquid).
      Stronger effects on craving were associated with satisfaction with e-cigarettes,
      and with reporting that e-cigarettes helped to quit smoking. Participants who
      reported the strongest effects on craving for tobacco were the most dependent on
      the e-cigarette and had the strongest urges to vape. CONCLUSIONS: From a public
      health perspective, there is a trade-off between e-cigarettes that provide high
      levels of nicotine, high satisfaction and more effects on craving for tobacco,
      but may also be addictive, and e-cigarettes that contain less nicotine and are
      less addictive, but are also less satisfactory and less efficient at relieving
      craving and at helping dependent smokers quit smoking. This trade-off must be
      kept in mind when regulating e-cigarettes.

PMID- 25592456
TI  - Using critical care chest ultrasonic examination in emergency consultation: a
      pilot study.
AB  - The purpose of this study was to investigate the effects of critical care chest
      ultrasonic examination (CCUE) by intensivist on the diagnosis and treatment
      decisions in emergent consultation for patients who may have a problem-need
      transfer to an intensive care unit (ICU). A total of 130 patients who required
      emergent consultation in the ordinary wards were included in this study. Patients
      were randomly divided into conventional group (n = 63) and CCUE group (n = 67,
      added CCUE). The two groups showed no significant differences in general clinical
      information or final diagnosis (p > 0.05). The CCUE group had a shorter time to
      preliminary diagnosis, final diagnosis, treatment response and X-ray/computed
      tomography examination; a delay in ICU transfer and ICU stay days (3.9 +/- 1.2
      vs. 5.4 +/- 1.9 d, p < 0.05) and a higher diagnostic accuracy than the
      conventional group (p < 0.001). In conclusion, CCUE could help early diagnosis
      and therapy for the patient who may need to transfer to the ICU and reduce the
      ICU stay for in-hospital patients in emergent consultation.

PMID- 25592457
TI  - A theoretical study of inertial cavitation from acoustic radiation force impulse
      imaging and implications for the mechanical index.
AB  - The mechanical index (MI) attempts to quantify the likelihood that exposure to
      diagnostic ultrasound will produce an adverse biological effect by a non-thermal
      mechanism. The current formulation of the MI implicitly assumes that the acoustic
      field is generated using the short pulse durations appropriate to B-mode imaging.
      However, acoustic radiation force impulse (ARFI) imaging employs high-intensity
      pulses up to several hundred acoustic periods long. The effect of increased pulse
      durations on the thresholds for inertial cavitation was studied computationally
      in water, urine, blood, cardiac and skeletal muscle, brain, kidney, liver and
      skin. The results indicate that, although the effect of pulse duration on
      cavitation thresholds in the three liquids can be considerable, reducing them by,
      for example, 6%-24% at 1 MHz, the effect on tissue is minor. More importantly,
      the frequency dependence of the MI appears to be unnecessarily conservative; that
      is, the magnitude of the exponent on frequency could be increased to 0.75.
      Comparison of these theoretical results with experimental measurements suggests
      that some tissues do not contain the pre-existing, optimally sized bubbles
      assumed for the MI. This means that in these tissues, the MI is not necessarily a
      strong predictor of the probability of an adverse biological effect.

PMID- 25592458
TI  - Subharmonic, non-linear fundamental and ultraharmonic imaging of microbubble
      contrast at high frequencies.
AB  - There is increasing use of ultrasound contrast agent in high-frequency ultrasound
      imaging. However, conventional contrast detection methods perform poorly at high
      frequencies. We performed systematic in vitro comparisons of subharmonic, non
      linear fundamental and ultraharmonic imaging for different depths and ultrasound
      contrast agent concentrations (Vevo 2100 system with MS250 probe and MicroMarker
      ultrasound contrast agent, VisualSonics, Toronto, ON, Canada). We investigated 4
      , 6- and 10-cycle bursts at three power levels with the following pulse
      sequences: B-mode, amplitude modulation, pulse inversion and combined pulse
      inversion/amplitude modulation. The contrast-to-tissue (CTR) and contrast-to
      artifact (CAR) ratios were calculated. At a depth of 8 mm, subharmonic pulse
      inversion imaging performed the best (CTR = 26 dB, CAR = 18 dB) and at 16 mm, non
      linear amplitude modulation imaging was the best contrast imaging method (CTR =
      10 dB). Ultraharmonic imaging did not result in acceptable CTRs and CARs. The
      best candidates from the in vitro study were tested in vivo in chicken embryo and
      mouse models, and the results were in a good agreement with the in vitro
      findings.

PMID- 25592459
TI  - Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi-
      Metabolites, enzymes and residual antibacterial activity.
AB  - A group of white rot fungi (Irpex lacteus, Panus tigrinus, Dichomitus squalens,
      Trametes versicolor and Pleurotus ostreatus) was investigated for the
      biodegradation of norfloxacin (NOR), ofloxacin (OF) and ciprofloxacin (CIP). The
      selected fluoroquinolones were readily degraded almost completely by I. lacteus
      and T. versicolor within 10 and 14 d of incubation in liquid medium,
      respectively. The biodegradation products were identified by liquid
      chromatography-mass spectrometry. The analyses indicated that the fungi use
      similar mechanisms to degrade structurally related antibiotics. The piperazine
      ring of the molecules is preferably attacked via either substitution or/and
      decomposition. In addition to the degradation efficiency, attention was devoted
      to the residual antibiotic activities estimated using Gram-positive and Gram
      negative bacteria. Only I. lacteus was able to remove the antibiotic activity
      during the course of the degradation of NOR and OF. The product-effect
      correlations evaluated by Principal Component Analysis (PCA) enabled elucidation
      of the participation of the individual metabolites in the residual antibacterial
      activity. Most of the metabolites correlated with the antibacterial activity,
      explaining the rather high residual activity remaining after the biodegradation.
      PCA of ligninolytic enzyme activities indicated that manganese peroxidase might
      participate in the degradation.

PMID- 25592460
TI  - Assessment of trace metals contamination level, bioavailability and toxicity in
      sediments from Dakar coast and Saint Louis estuary in Senegal, West Africa.
AB  - Trace metals have the potential to associate with sediments that have been
      recognised as significant source of contamination for the benthic environment.
      The current study aims assessing the trace metals contamination level in
      sediments from Dakar coast and Saint Louis estuary, and to examine their
      bioavailability to predict potential toxicity of sediments. Surface sediment
      samples were collected between June 2012 and January 2013 in three sampling
      periods from eight stations. Trace metals were analysed using inductively coupled
      plasma-optical emission spectrometer. Geoaccumulation indexes (Igeo) showed
      strong pollution by Cd, Cr, Cu and Pb confirmed by enrichment factor (EF)
      suggesting that these metals derived from anthropogenic sources. Toxicity indexes
      exceeded one in several sites suggesting the potential effects on sediment
      dwelling organisms, which may constitute a risk to populations' health. However,
      seasonal variability of metal bioavailability was noted, revealing the best
      period to monitor metal contamination. From an ecotoxicological point of view,
      concentrations of Cd, Cr, Cu and Pb were above the effects range low threshold
      limit of the sediment quality guidelines for adverse biological effects. In
      addition, with Pb concentrations above the effect range medium values in some
      sites, biological effects may occur. 

PMID- 25592461
TI  - DNA damage in grasshopper Chorthippus brunneus (Orthoptera) hatchlings following
      paraquat exposure.
AB  - Comet assay was applied to study genotoxic damage induced by paraquat (PQ) in
      brain cells of Chorthippus brunneus (Insecta: Orthoptera) hatchlings. Percentage
      of the comet fluorescence in the tail (TDNA), length of the comet tail (TL) and
      Olive tail moment (OTM) were used for quantitative assessment of the DNA damage.
      Multiple regression analysis supplemented standard statistical elaboration of the
      results. Increasing PQ concentrations applied either directly to the brain cells
      suspension (10, 50, and 250 MUM PQ final concentration--in vitro protocol) or
      indirectly (50, 250, and 1250 MUM PQ final concentration--in vivo protocol)
      provoked significant increase of oxidative damage to DNA (higher median TDNA and
      OTM values). The damage increased with time of exposure (0, 5, 15, and 30 min)
      following in vitro application, but decreased in longer interval (3 vs 24 h)
      after in vivo administration of paraquat. On contrary, median TL values did not
      correlate with paraquat concentration irrespectively of the exposure protocol.
      Possible reason of this discrepancy in light of paraquat toxicity is discussed.

PMID- 25592462
TI  - Optimizing fish sampling for fish-mercury bioaccumulation factors.
AB  - Fish Bioaccumulation Factors (BAFs; ratios of mercury (Hg) in fish (Hgfish) and
      water (Hgwater)) are used to develop total maximum daily load and water quality
      criteria for Hg-impaired waters. Both applications require representative Hgfish
      estimates and, thus, are sensitive to sampling and data-treatment methods. Data
      collected by fixed protocol from 11 streams in 5 states distributed across the US
      were used to assess the effects of Hgfish normalization/standardization methods
      and fish-sample numbers on BAF estimates. Fish length, followed by weight, was
      most correlated to adult top-predator Hgfish. Site-specific BAFs based on length
      normalized and standardized Hgfish estimates demonstrated up to 50% less
      variability than those based on non-normalized Hgfish. Permutation analysis
      indicated that length-normalized and standardized Hgfish estimates based on at
      least 8 trout or 5 bass resulted in mean Hgfish coefficients of variation less
      than 20%. These results are intended to support regulatory mercury monitoring and
      load-reduction program improvements. 

PMID- 25592463
TI  - Occurrence, variability and human exposure to Polychlorinated Dibenzo-p-dioxins
      (PCDDs), Polychlorinated Dibenzofurans (PCDFs) and Dioxin-Like Polychlorinated
      Biphenyls (DL-PCBs) in dairy products from Chile during the 2011-2013 survey.
AB  - Levels, congener profiles of PCDD/Fs, DL-PCBs and human exposure for these
      xenobiotics never have been reported in Chile. For that purpose 102 raw cow milk
      samples were collected from seven different regions of Chile during 2011 until
      2013. The highest mean level for PCDD/Fs, corresponds to 0.32 pg WHO-TEQ2005 g(
      1) fat (2012) and for DL-PCBs 0.17 pg WHO-TEQ2005 g(-1) fat (2011), using the
      upper bound approach. Penta and tetra chlorinated congeners dominated PCDD/Fs
      profiles in a WHO-TEQ2005 basis during the survey. In the case of DL-PCBs, PCB
      126 dominated the profiles with 89%. Statistical analysis showed significant
      difference among years only in DL-PCBs residues. Also dietary intake was
      estimated, and the highest level for total sum of PCDD/Fs and DL-PCBs for adult
      was 0.16 pg WHO-TEQ kg(-1) b.w d(-1) (2011) and for children correspond to 0.65
      pg WHO-TEQ kg(-1) b.wd(-1) (2011). Concentrations and dietary intake for the
      studied compounds in milk and butter samples were below international and
      national regulations.

PMID- 25592464
TI  - Antimony retention and release from drained and waterlogged shooting range soil
      under field conditions.
AB  - Many soils polluted by antimony (Sb) are subject to fluctuating waterlogging
      conditions; yet, little is known about how these affect the mobility of this
      toxic element under field conditions. Here, we compared Sb leaching from a
      calcareous shooting range soil under drained and waterlogged conditions using
      four large outdoor lysimeters. After monitoring the leachate samples taken at bi
      weekly intervals for >1.5 years under drained conditions, two of the lysimeters
      were subjected to waterlogging with a water table fluctuating according to
      natural rainfall water infiltration. Antimony leachate concentrations under
      drained conditions showed a strong seasonal fluctuation between 110 MUg L(-1) in
      summer and <40 MUg L(-1) in winter, which closely correlated with fluctuations in
      dissolved organic carbon (DOC) concentrations. With the development of anaerobic
      conditions upon waterlogging, Sb in leachate decreased to 2-5 MUg L(-1) Sb and
      remained stable at this level. Antimony speciation measurements in soil solution
      indicated that this decrease in Sb(V) concentrations was attributable to the
      reduction of Sb(V) to Sb(III) and the stronger sorption affinity of the latter to
      iron (Fe) (hydr)oxide phases. Our results demonstrate the importance of
      considering seasonal and waterlogging effects in the assessment of the risks from
      Sb-contaminated sites.

PMID- 25592465
TI  - Extending the working pH of nitrobenzene degradation using
      ultrasonic/heterogeneous Fenton to the alkaline range via amino acid
      modification.
AB  - Oxides of iron, alpha-Fe2O3 (I), and copper, CuO (II) prepared by usual
      precipitation method without surfactant were used at room temperature in the
      process of nitrobenzene (10mgL(-1)) degradation at different pH values with
      ultrasonic at 20kHz. The degradation was complete in 20 and 30min for (I) and
      (II), respectively in the pH range 2-7 using1.0gL(-1) of solids and 10mM of H2O2.
      A remarkable decrease in degradation efficiency was recorded on increasing the pH
      to values higher than the neutral range. This loss in efficiency was cancelled to
      a great extent through modifying the used oxides with amino acids. Arginine
      showed higher improving effect to (II) (1:1 weight ration) than glycine or
      glutamic acid. Modification of both oxides with increasing amounts of arginine
      increased the degradation efficiency of (I) in a more regular way than in case of
      (II). However, the extent of improvement due to amino acid modification was
      higher in case of (II) because of its originally low degradation efficiency in
      strongly alkaline media.

PMID- 25592466
TI  - Prostate cancer: The main risk and protective factors-Epigenetic modifications.
AB  - With 13 million new cases worldwide every year, prostate cancer is as a very real
      public health concern. Prostate cancer is common in over-50s men and the sixth
      leading cause of cancer-related death in men worldwide. Like all cancers,
      prostate cancer is multifactorial - there are non-modifiable risk factors like
      heredity, ethnicity and geographic location, but also modifiable risk factors
      such as diet. Diet-cancer linkages have risen to prominence in the last few
      years, with accruing epidemiological data pointing to between-population
      incidence differentials in numerous cancers. Indeed, there are correlations
      between fat-rich diet and risk of hormone-dependent cancers like prostate cancer
      and breast cancer. Diet is a risk factor for prostate cancer, but certain
      micronutrients in specific diets are considered protective factors against
      prostate cancer. Examples include tomato lycopene, green tea epigallocatechin
      gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer
      protective effects via anti-oxidant pathways and inhibition of cell
      proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly
      genistein and daidzein, which are the best-researched to date. Soy phytoestrogens
      are nonsteroid molecules whose structural similarity lends them the ability to
      mimic the effects of 17beta-estradiol. On top of anti-oxidant effects, there is
      evidence that soy phytoestrogens can modulate the epigenetic modifications found
      in prostate cancer. We also studied the impact of phytoestrogens on epigenetic
      modifications in prostate cancer, with special focus on DNA methylation, miRNA
      mediated regulation and histone modifications. 

PMID- 25592467
TI  - Rapid in vivo validation of candidate drivers derived from the PTEN-mutant
      prostate metastasis genome.
AB  - Human genome analyses have revealed that increasing gene copy number alteration
      is a driving force of incurable cancer of the prostate (CaP). Since most of the
      affected genes are hidden within large amplifications or deletions, there is a
      need for fast and faithful validation of drivers. However, classic genetic CaP
      engineering in mouse makes this a daunting task because generation, breeding
      based combination of alterations and non-invasive monitoring of disease are too
      time consuming and costly. To address the unmet need, we recently developed
      RapidCaP mice, which endogenously recreate human PTEN-mutant metastatic CaP based
      on Cre/Luciferase expressing viral infection, that is guided to
      Pten(loxP)/Trp53(loxP) prostate. Here we use a sensitized, non-metastatic
      Pten/Trp53-mutant RapidCaP system for functional validation of human metastasis
      drivers in a much accelerated time frame of only 3-4months. We used in vivo RNAi
      to target three candidate tumor suppressor genes FOXP1, RYBP and SHQ1, which
      reside in a frequent deletion on chromosome 3p and show that Shq1 cooperates with
      Pten and p53 to suppress metastasis. Our results thus demonstrate that the
      RapidCaP system forms a much needed platform for in vivo screening and validation
      of genes that drive endogenous lethal CaP. 

PMID- 25592468
TI  - Morbidity, mortality, cost, and survival estimates of gastrointestinal
      anastomotic leaks.
AB  - BACKGROUND: Anastomotic leak, a potentially deadly postoperative occurrence,
      particularly interests surgeons performing gastrointestinal procedures. We
      investigated incidence, cost, and impact on survival of anastomotic leak in
      gastrointestinal surgical procedures at an academic center. STUDY DESIGN: We
      conducted a chart review of American College of Surgeons NSQIP operative
      procedures with gastrointestinal anastomosis from January 1, 2003 through April
      30, 2006. Each case with an American College of Surgeons NSQIP 30-day
      postoperative complication was systematically reviewed for evidence of
      anastomotic leak for 12 months after the operative date. We tracked patients for
      up to 10 years to determine survival. Morbidity, mortality, and cost for patients
      with gastrointestinal anastomotic leaks were compared with patients with
      anastomoses that remained intact. RESULTS: Unadjusted analyses revealed
      significant differences between patients who had anastomotic leaks develop and
      those who did not: morbidity (98.0% vs. 28.4%; p < 0.0001), length of stay (13
      vs. 5 days; p <= 0.0001), 30-day mortality (8.4% vs. 2.5%; p < 0.0001), long-term
      mortality (36.4% vs. 20.0%; p <= 0.0001), and hospital costs (chi-square [2] =
      359.8; p < 0.0001). Multivariable regression demonstrated that anastomotic leak
      was associated with congestive heart failure (odds ratio [OR] = 31.5; 95% CI, 2.6
      381.4; p = 0.007), peripheral vascular disease (OR = 4.6; 95% CI, 1.0-20.5; p =
      0.048), alcohol abuse (OR = 3.7; 95% CI, 1.6-8.3; p = 0.002), steroid use (OR =
      2.3; 95% CI: 1.1-5.0; p = 0.027), abnormal sodium (OR = 0.4; 95% CI, 0.2-0.7; p =
      0.002), weight loss (OR = 0.2; 95% CI, 0.06-0.7; p = 0.011), and location of
      anastomosis: rectum (OR = 14.0; 95% CI, 2.6-75.5; p = 0.002), esophagus (OR =
      13.0; 95% CI, 3.6-46.2; p < 0.0001), pancreas (OR = 12.4; 95% CI, 3.3-46.2; p <
      0.0001), small intestine (OR = 6.9; 95% CI, 1.8-26.4; p = 0.005), and colon (OR =
      5.2; 95% CI, 1.5-17.7; p = 0.009). CONCLUSIONS: Significant morbidity, mortality,
      and cost accompany gastrointestinal anastomotic leaks. Patients who experience an
      anastomotic leak have lower rates of survival at 30 days and long term.

PMID- 25592470
TI  - The wirsung duct in acute pancreatitis: its morphoclinical relevance.

PMID- 25592471
TI  - Surgical strategy for incidental gallbladder cancer.

PMID- 25592473
TI  - When foots come first: early signs of podocyte injury in Fabry nephropathy
      without proteinuria.

PMID- 25592469
TI  - Cyst fluid biomarkers for intraductal papillary mucinous neoplasms of the
      pancreas: a critical review from the international expert meeting on pancreatic
      branch-duct-intraductal papillary mucinous neoplasms.

PMID- 25592474
TI  - Rational selection of experimental readout and intervention sites for reducing
      uncertainties in computational model predictions.
AB  - BACKGROUND: Understanding the dynamics of biological processes can substantially
      be supported by computational models in the form of nonlinear ordinary
      differential equations (ODE). Typically, this model class contains many unknown
      parameters, which are estimated from inadequate and noisy data. Depending on the
      ODE structure, predictions based on unmeasured states and associated parameters
      are highly uncertain, even undetermined. For given data, profile likelihood
      analysis has been proven to be one of the most practically relevant approaches
      for analyzing the identifiability of an ODE structure, and thus model
      predictions. In case of highly uncertain or non-identifiable parameters, rational
      experimental design based on various approaches has shown to significantly reduce
      parameter uncertainties with minimal amount of effort. RESULTS: In this work we
      illustrate how to use profile likelihood samples for quantifying the individual
      contribution of parameter uncertainty to prediction uncertainty. For the
      uncertainty quantification we introduce the profile likelihood sensitivity (PLS)
      index. Additionally, for the case of several uncertain parameters, we introduce
      the PLS entropy to quantify individual contributions to the overall prediction
      uncertainty. We show how to use these two criteria as an experimental design
      objective for selecting new, informative readouts in combination with
      intervention site identification. The characteristics of the proposed multi
      criterion objective are illustrated with an in silico example. We further
      illustrate how an existing practically non-identifiable model for the chlorophyll
      fluorescence induction in a photosynthetic organism, D. salina, can be rendered
      identifiable by additional experiments with new readouts. CONCLUSIONS: Having
      data and profile likelihood samples at hand, the here proposed uncertainty
      quantification based on prediction samples from the profile likelihood provides a
      simple way for determining individual contributions of parameter uncertainties to
      uncertainties in model predictions. The uncertainty quantification of specific
      model predictions allows identifying regions, where model predictions have to be
      considered with care. Such uncertain regions can be used for a rational
      experimental design to render initially highly uncertain model predictions into
      certainty. Finally, our uncertainty quantification directly accounts for
      parameter interdependencies and parameter sensitivities of the specific
      prediction.

PMID- 25592475
TI  - Ectopic expression of fatty acid-binding protein 4 in the glomerulus is
      associated with proteinuria and renal dysfunction.
AB  - BACKGROUND/AIMS: Fatty acid-binding proteins (FABPs) are a family of
      intracellular lipid chaperones. Among FABPs, FABP1 (liver FABP) is expressed in
      proximal tubular epithelial cells in the kidney, and urinary FABP1 has been
      reported to reflect damage of proximal tubular epithelial cells. However, roles
      of other FABP isoforms in renal pathologies have not been reported. Recently,
      FABP4 (adipocyte FABP/aP2) was reported to be expressed in peritubular
      capillaries (PTCs), but not in glomerular capillaries in the normal kidney. We
      examined the hypothesis that pathological conditions alter the level and
      localization of FABP4 expression in the kidney, which mediates renal dysfunction.
      METHODS: A total of 112 consecutive patients who underwent renal biopsy were
      retrospectively enrolled. Expression of FABP4 protein and mRNA in the kidney was
      examined by immunohistochemistry and in situ hybridization, respectively. The
      ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area),
      urinary protein level (U-Protein), and change in estimated glomerular filtration
      rate (eGFR) 1 year after biopsy were examined. RESULTS: FABP4 protein and mRNA
      were expressed not only in PTCs, but also in endothelial cells and macrophages in
      the glomerulus. G-FABP4-Area was correlated with U-Protein (r = 0.497, p <
      0.001). As a subanalysis, in patients with IgA nephropathy (n = 34), G-FABP4-Area
      was significantly larger in cases with an endocapillary proliferative lesion, and
      change in eGFR was negatively correlated with G-FABP4-Area at baseline (r = 
      0.537, p = 0.008). CONCLUSION: Ectopic FABP4 expression in the glomerulus is
      induced by renal diseases and is closely associated with proteinuria and renal
      dysfunction.

PMID- 25592476
TI  - Evolution and emergence of infectious diseases in theoretical and real-world
      networks.
AB  - One of the most important advancements in theoretical epidemiology has been the
      development of methods that account for realistic host population structure. The
      central finding is that heterogeneity in contact networks, such as the presence
      of 'superspreaders', accelerates infectious disease spread in real epidemics.
      Disease control is also complicated by the continuous evolution of pathogens in
      response to changing environments and medical interventions. It remains unclear,
      however, how population structure influences these adaptive processes. Here we
      examine the evolution of infectious disease in empirical and theoretical
      networks. We show that the heterogeneity in contact structure, which facilitates
      the spread of a single disease, surprisingly renders a resident strain more
      resilient to invasion by new variants. Our results suggest that many host contact
      structures suppress invasion of new strains and may slow disease adaptation.
      These findings are important to the natural history of disease evolution and the
      spread of drug-resistant strains. 

PMID- 25592477
TI  - High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease
      treated with early high-dose corticosteroids.
AB  - PURPOSE: To analyse the rate of clinical recurrences in Brazilian patients with
      Vogt-Koyanagi-Harada (VKH) disease after early high-dose corticosteroid
      treatment. METHODS: Retrospective study including patients treated with early
      high-dose corticosteroids (prednisone, 1-1.5 mg/kg/day, or 3-day 1 g
      methylprednisolone pulsetherapy) within 1 month from disease onset followed by
      slow taper (at least 6 months). Patients with a minimum 12-month follow-up were
      subdivided based on the presence of disease recurrence or persistence after 6
      months from initial presentation into: acute-resolved (AR, no recurrences),
      chronic-recurrent (CR), and chronic-recurrent with subretinal fibrosis (SRF).
      Recurrences were defined as the presence of clinical and/or fluorescein
      angiography findings. RESULTS: Twenty-nine patients (58 eyes) with a median
      follow-up of 65 months were included. Six (21 %), 11 (38 %) and 12 (41 %)
      patients were allocated to AR, CR, and SRF groups respectively. Though having
      received treatment within 1 month of onset, median time to initial treatment
      differed among groups (11, 15, and 25 days, in AR, CR, and SRF groups
      respectively). Intensity of immunosuppression, cataract development, and longer
      time to achieve logMAR visual acuity <=0.8 differed significantly among the
      groups, being more severe in SRF group. HLA-DRB1*0405 allele followed the same
      trend, though not reaching significance (0.5 in AR group, 0.6 in CR, and 0.8 in
      SRF). CONCLUSION: VKH disease in Brazilian patients evolved to chronic-recurrent
      disease in 79 % of cases; 38 % developed subretinal fibrosis, in spite of similar
      initial treatment regimens. Time to initiate treatment influenced outcomes.

PMID- 25592478
TI  - Cataract surgery in infants with microphthalmos.
AB  - PURPOSE: To report the postoperative outcomes of cataract surgery in
      microphthalmic eyes of infants. METHODS: This prospective observational study was
      carried out on 20 infants with microphthalmos with visually significant cataract.
      Microphthalmos was defined as axial length of the globe 16.50 mm or less. We
      excluded eyes with ocular trauma, inflammation, posterior hyperplastic primary
      vitreous or a tractional retinal detachment, aniridia, or chorioretinal coloboma.
      All the infants enrolled in this study underwent phacoaspiration with primary
      posterior capsulotomy, anterior vitrectomy, and peripheral iridectomy.
      Intraocular lens was not implanted in these children. Post-operative evaluation
      included refractive errors, irregularity of pupil, posterior synechiae, visual
      axis obscuration, and intraocular pressure. These children were followed up for a
      minimum of 12 months. RESULTS: We evaluated 37 eyes of 20 infants, of whom 17
      infants had bilateral and three infants had unilateral cataract. The mean age of
      the children and the mean axial length at the time of surgery were 3.78 +/- 2.25
      months and 15.76 +/- 0.56 mm respectively. The complications observed were
      irregularity of pupil in seven eyes (18.9 %), glaucoma in five eyes (13.5 %),
      posterior synechiae in two eyes (5.2 %), visual axis obscuration due to posterior
      capsule opacification (PCO) in two eyes (5.2 %) and phthisis in one eye (2.7 %).
      CONCLUSION: Infants achieved a favorable outcome after phacoaspiration with
      primary posterior capsulotomy with anterior vitrectomy. However, these children
      must be followed up to detect and treat postoperative complications such as
      visual axis obscuration, posterior synechiae, and glaucoma to achieve optimal
      outcome.

PMID- 25592479
TI  - Adapting simultaneous analysis phylogenomic techniques to study complex disease
      gene relationships.
AB  - The characterization of complex diseases remains a great challenge for biomedical
      researchers due to the myriad interactions of genetic and environmental factors.
      Network medicine approaches strive to accommodate these factors holistically.
      Phylogenomic techniques that can leverage available genomic data may provide an
      evolutionary perspective that may elucidate knowledge for gene networks of
      complex diseases and provide another source of information for network medicine
      approaches. Here, an automated method is presented that leverages publicly
      available genomic data and phylogenomic techniques, resulting in a gene network.
      The potential of approach is demonstrated based on a case study of nine genes
      associated with Alzheimer Disease, a complex neurodegenerative syndrome. The
      developed technique, which is incorporated into an update to a previously
      described Perl script called "ASAP," was implemented through a suite of Ruby
      scripts entitled "ASAP2," first compiles a list of sequence-similarity based
      orthologues using PSI-BLAST and a recursive NCBI BLAST+ search strategy, then
      constructs maximum parsimony phylogenetic trees for each set of nucleotide and
      protein sequences, and calculates phylogenetic metrics (Incongruence Length
      Difference between orthologue sets, partitioned Bremer support values, combined
      branch scores, and Robinson-Foulds distance) to provide an empirical assessment
      of evolutionary conservation within a given genetic network. In addition to the
      individual phylogenetic metrics, ASAP2 provides results in a way that can be used
      to generate a gene network that represents evolutionary similarity based on
      topological similarity (the Robinson-Foulds distance). The results of this study
      demonstrate the potential for using phylogenomic approaches that enable the study
      of multiple genes simultaneously to provide insights about potential gene
      relationships that can be studied within a network medicine framework that may
      not have been apparent using traditional, single-gene methods. Furthermore, the
      results provide an initial integrated evolutionary history of an Alzheimer
      Disease gene network and identify potentially important co-evolutionary
      clustering that may warrant further investigation. 

PMID- 25592480
TI  - Dose-dependent neuroprotection of delta-opioid peptide [D-Ala(2), D-Leu(5)]
      enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into
      the abdominal aorta in rabbits.
AB  - OBJECTIVE: In our prior study, we showed that delta-opioid peptide [D-Ala(2), D
      Leu(5)] enkephalin (DADLE), by regional perfusion into the abdominal aorta, could
      protect the spinal cord against ischemia-reperfusion (I/R) injury caused by
      aortic occlusion. However, the relative dose-response effects of DADLE still
      remain unclear. This study investigated whether DADLE has a dose-dependent
      efficiency on spinal cord I/R injury. METHODS: New Zealand White rabbits were
      randomly divided into one of six groups: normal saline (NS; n = 8), DADLE (D)
      groups D0.0005 (n = 8), D0.005 (n = 8), D0.05 (n = 8), and D0.5 mg/kg (n = 8),
      and a sham group (n = 6). In the NS and DADLE groups, spinal cord ischemia was
      induced by infrarenal aortic occlusion for 30 minutes. During the occlusion, the
      same volume of NS or DADLE at the indicated doses was infused continuously
      through a catheter to the distally clamped abdominal aorta. Heart rate, blood
      pressure, and core temperature were monitored continuously to evaluate the
      potential adverse effects of DADLE. Neurologic behavioral function was assessed
      with the Tarlov scale system at 1, 6, 24, 48, and 72 hours after reperfusion.
      Neuronal injury evaluation in the ventral horn of the gray matter was evaluated
      by counting the normal motor neurons at 72 hours after reperfusion. RESULTS: The
      therapeutic benefits increased at the doses of DADLE from 0.0005 to 0.05 mg/kg
      and decreased at 0.5 mg/kg, whereas the hemodynamic parameter was suppressed
      temporarily at the dose of 0.5 mg/kg. CONCLUSIONS: These data revealed that
      regional administration of DADLE through the abdominal aorta provided dose
      dependent protection on spinal cord I/R in rabbits.

PMID- 25592481
TI  - Using patient experiences on Dutch social media to supervise health care
      services: exploratory study.
AB  - BACKGROUND: Social media has become mainstream and a growing number of people use
      it to share health care-related experiences, for example on health care rating
      sites. These users' experiences and ratings on social media seem to be associated
      with quality of care. Therefore, information shared by citizens on social media
      could be of additional value for supervising the quality and safety of health
      care services by regulatory bodies, thereby stimulating participation by
      consumers. OBJECTIVE: The objective of the study was to identify the added value
      of social media for two types of supervision by the Dutch Healthcare Inspectorate
      (DHI), which is the regulatory body charged with supervising the quality and
      safety of health care services in the Netherlands. These were (1) supervision in
      response to incidents reported by individuals, and (2) risk-based supervision.
      METHODS: We performed an exploratory study in cooperation with the DHI and
      searched different social media sources such as Twitter, Facebook, and healthcare
      rating sites to find additional information for these incidents and topics, from
      five different sectors. Supervision experts determined the added value for each
      individual result found, making use of pre-developed scales. RESULTS: Searches in
      social media resulted in relevant information for six of 40 incidents studied and
      provided relevant additional information in 72 of 116 cases in risk-based
      supervision of long-term elderly care. CONCLUSIONS: The results showed that
      social media could be used to include the patient's perspective in supervision.
      However, it appeared that the rating site ZorgkaartNederland was the only source
      that provided information that was of additional value for the DHI, while other
      sources such as forums and social networks like Twitter and Facebook did not
      result in additional information. This information could be of importance for
      health care inspectorates, particularly for its enforcement by risk-based
      supervision in care of the elderly. Further research is needed to determine the
      added value for other health care sectors.

PMID- 25592483
TI  - Influence of nanoparticles accumulation on optical properties of human normal and
      cancerous liver tissue in vitro estimated by OCT.
AB  - In this work, the potential use of nanoparticles as contrast agents by using
      spectral domain optical coherence tomography (SD-OCT) in liver tissue was
      demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in
      human normal and cancerous liver tissues in vitro, respectively. Each sample was
      monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring
      showed that, after application of gold nanoparticles, the OCT signal intensities
      of normal liver and cancerous liver tissue both increase with time, and the
      larger nanoparticles tend to produce a greater signal enhancement in the same
      type of tissue. The results show that the values of attenuation coefficients have
      significant differences between normal liver tissue and cancerous liver tissue.
      In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm
      gold nanoparticles in liver tissues. 

PMID- 25592482
TI  - From "weight of evidence" to quantitative data integration using multicriteria
      decision analysis and Bayesian methods.
AB  - "Weighing" available evidence in the process of decision-making is unavoidable,
      yet it is one step that routinely raises suspicions: what evidence should be
      used, how much does it weigh, and whose thumb may be tipping the scales? This
      commentary aims to evaluate the current state and future roles of various types
      of evidence for hazard assessment as it applies to environmental health. In its
      recent evaluation of the US Environmental Protection Agency's Integrated Risk
      Information System assessment process, the National Research Council committee
      singled out the term "weight of evidence" (WoE) for critique, deeming the process
      too vague and detractive to the practice of evaluating human health risks of
      chemicals. Moving the methodology away from qualitative, vague and controversial
      methods towards generalizable, quantitative and transparent methods for
      appropriately managing diverse lines of evidence is paramount for both regulatory
      and public acceptance of the hazard assessments. The choice of terminology
      notwithstanding, a number of recent Bayesian WoE-based methods, the emergence of
      multi criteria decision analysis for WoE applications, as well as the general
      principles behind the foundational concepts of WoE, show promise in how to move
      forward and regain trust in the data integration step of the assessments. We
      offer our thoughts on the current state of WoE as a whole and while we
      acknowledge that many WoE applications have been largely qualitative and
      subjective in nature, we see this as an opportunity to turn WoE towards a
      quantitative direction that includes Bayesian and multi criteria decision
      analysis.

PMID- 25592484
TI  - Thorough subcells diagnosis in a multi-junction solar cell via absolute
      electroluminescence-efficiency measurements.
AB  - World-wide studies on multi-junction (tandem) solar cells have led to record
      breaking improvements in conversion efficiencies year after year. To obtain
      detailed and proper feedback for solar-cell design and fabrication, it is
      necessary to establish standard methods for diagnosing subcells in fabricated
      tandem devices. Here, we propose a potential standard method to quantify the
      detailed subcell properties of multi-junction solar cells based on absolute
      measurements of electroluminescence (EL) external quantum efficiency in addition
      to the conventional solar-cell external-quantum-efficiency measurements. We
      demonstrate that the absolute-EL-quantum-efficiency measurements provide I-V
      relations of individual subcells without the need for referencing measured I-V
      data, which is in stark contrast to previous works. Moreover, our measurements
      quantify the absolute rates of junction loss, non-radiative loss, radiative loss,
      and luminescence coupling in the subcells, which constitute the "balance sheets"
      of tandem solar cells. 

PMID- 25592485
TI  - Labour promises healthier food for children and standardised tobacco packaging.

PMID- 25592486
TI  - Technical developments of functional electrical stimulation to correct drop foot:
      sensing, actuation and control strategies.
AB  - This work presents a review on the technological advancements over the last
      decades of functional electrical stimulation based neuroprostheses to correct
      drop foot. Functional electrical stimulation is a technique that has been put
      into practice for several years now, and has been shown to functionally restore
      and rehabilitate individuals with movement disorders, such as stroke, multiple
      sclerosis and traumatic brain injury, among others. The purpose of this technical
      review is to bring together information from a variety of sources and shed light
      on the field's most important challenges, to help in identifying new research
      directions. The review covers the main causes of drop foot and its associated
      gait implications, along with several functional electrical stimulation-based
      neuroprostheses used to correct it, developed within academia and currently
      available in the market. These systems are thoroughly analyzed and discussed with
      particular emphasis on actuation, sensing and control of open- and closed-loop
      architectures. In the last part of this work, recommendations on future research
      directions are suggested. 

PMID- 25592488
TI  - Non-invasive ventilation in patients with hematologic malignancy: a new
      prospective.
AB  - Immunosuppressed patients are usually considered together without distinction.
      However, patients with hematologic malignancy should be included in a different
      subcategory. The outcome of this population has improved over the years. However,
      mortality rate continues to be high, especially when respiratory complications
      are present and mechanical ventilation is required. Non-invasive ventilation
      (NIV) demonstrated its efficacy on the process of respiratory failure improving
      clinical outcomes in patients of different diagnoses. Recommendations of
      guidelines to use NIV in immunosuppressed patients have been quite prudent.
      However, NIV has been recently applied in hematologic malignancy patients during
      an early or/and late respiratory failure, showing a favorable impact improving
      the outcome. At an early stage, one study showed CPAP to reduce respiratory
      complications and to improve the outcome of mortality rate from 75% in the
      control group to 15% in the treatment group, when compared to oxygen therapy. In
      other two randomized control trials, NIV in comparison to invasive mechanical
      ventilation demonstrated to reduce mortality rate from 100% to 53-61%. As most of
      the non-randomized control trials applied NIV in a general population of
      immunosuppressed patients, results are very difficult to analyze. So far, the
      treatment starting, and duration time are still not clearly defined. Novel
      clinical trials should be performed to elucidate the appropriate application of
      NIV in this population. 

PMID- 25592489
TI  - Hyperglycemia and ambulatory surgery.
AB  - BACKGROUND: Perioperative hyperglycemia is associated with postoperative
      complications after major surgery. However, more than 50% of surgical procedures
      are performed in an ambulatory setting, where glucose is not routinely measured.
      The objectives of this study were to investigate the change in capillary glucose
      during ambulatory surgery, to identify patients at risk for perioperative
      increasing glucose and to evaluate whether hyperglycemia predisposes for
      complications after ambulatory surgery. METHODS: In this prospective multicenter
      cohort study, adult patients planned for ambulatory surgery, were included and
      capillary glucose was measured 1 hour before and 1 hour after surgery. Patients
      were contacted 90 days after surgery to determine the occurrence of postoperative
      complications. RESULTS: Nine hundred and nine patients were included, 48 (5.3%)
      patients had diabetes mellitus (DM). Overall median glucose increased from 5.4
      mmol L-1 preoperatively to 5.6 mmol L-1 postoperatively (P<0.001). Hyperglycemia,
      glucose >=7.8 mmol L-1, occurred in 8.8% of the patients. Dexamethasone
      administration (given in 406 [44.7%] patients) was a risk factor for glucose
      increase (P<0.001). Hyperglycemia was not a risk factor for postoperative
      complications (OR 1.19, 95%CI 0.57-2.48, P=0.646). However, prediagnosed DM was a
      risk factor for postoperative complications, independent of hyperglycemia (OR
      2.56, 95%CI 1.10-5.97, P=0.030). CONCLUSION: Minor ambulatory surgery is not
      associated with a clinically relevant increase in glucose. The very small glucose
      increase we observed could be attributed to the administration of dexamethasone
      for PONV prophylaxis. Hyperglycemia during ambulatory surgery is not associated
      with complications after discharge.

PMID- 25592487
TI  - Characterization of miRNAs associated with Botrytis cinerea infection of tomato
      leaves.
AB  - BACKGROUND: Botrytis cinerea Pers. Fr. is an important pathogen causing stem rot
      in tomatoes grown indoors for extended periods. MicroRNAs (miRNAs) have been
      reported as gene expression regulators related to several stress responses and B.
      cinerea infection in tomato. However, the function of miRNAs in the resistance to
      B. cinerea remains unclear. RESULTS: The miRNA expression patterns in tomato in
      response to B. cinerea stress were investigated by high-throughput sequencing. In
      total, 143 known miRNAs and seven novel miRNAs were identified and their
      corresponding expression was detected in mock- and B. cinerea-inoculated leaves.
      Among those, one novel and 57 known miRNAs were differentially expressed in B.
      cinerea-infected leaves, and 8 of these were further confirmed by quantitative
      reverse-transcription PCR (qRT-PCR). Moreover, five of these eight differentially
      expressed miRNAs could hit 10 coding sequences (CDSs) via CleaveLand pipeline and
      psRNAtarget program. In addition, qRT-PCR revealed that four targets were
      negatively correlated with their corresponding miRNAs (miR319, miR394, and
      miRn1). CONCLUSION: Results of sRNA high-throughput sequencing revealed that the
      upregulation of miRNAs may be implicated in the mechanism by which tomato respond
      to B. cinerea stress. Analysis of the expression profiles of B. cinerea
      responsive miRNAs and their targets strongly suggested that miR319, miR394, and
      miRn1 may be involved in the tomato leaves' response to B. cinerea infection.

PMID- 25592490
TI  - Different effects of cholestyramine on postprandial secretions of cholecystokinin
      and peptide YY in women with bulimia nervosa.
AB  - OBJECTIVE: Patients with bulimia nervosa (BN) are reported to have decreased
      postprandial levels of cholecystokinin (CCK) and peptide YY (PYY). Fatty
      nutrients are the most powerful stimulus for releasing these peptides.
      Cholestyramine is an anion exchanger which adsorbs bile salts and reduces the
      digestion of lipids, affecting the secretion of both CCK and PYY. To further
      characterise the physiology of these peptides in BN, we aimed to investigate the
      effects of cholestyramine (12 g, per os) or placebo administered with a high-fat
      meal on CCK and PYY secretions in bulimic versus healthy women. RESULTS:
      Postprandial CCK levels significantly increased in both healthy and bulimic women
      after placebo + the high-fat meal, without any significant difference between the
      two groups. Cholestyramine administration significantly increased postprandial
      CCK responses in both healthy and bulimic women; however, significantly lower CCK
      levels were observed in BN. Postprandial PYY levels significantly increased after
      placebo administration in healthy women after the high-fat meal, whereas no
      significant changes were found in bulimic women. Cholestyramine, administered
      with the high-fat meal, significantly reduced postprandial PYY response in
      healthy women, but not in bulimic women. Finally, there was a negative
      correlation of the area under the curve with respect to the increase of PYY
      (after placebo administration) with binge frequency in the bulimic women.
      CONCLUSION: In BN an altered postprandial secretion of CCK may be evidenced when
      cholestyramine is combined with a high-fat meal. Instead, the postprandial
      secretion of PYY is significantly blunted and not affected by cholestyramine
      administration.

PMID- 25592491
TI  - Upregulated Annexin A1 promotes cellular invasion in triple-negative breast
      cancer.
AB  - Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved
      in anti-inflammatory effects, regulation of cellular differentiation,
      proliferation and apoptosis. While many studies have investigated the ANXA1
      expression in various tumor types, the role of ANXA1 is not fully understood.
      Therefore, in the present study, we evaluated the ANXA1 expression in 211 breast
      cancer patients and compared the levels with clinicopathological factors. ANXA1
      was positively expressed in 31 (14.7%) of the 211 cases in our cohort, and these
      positive cases were associated with triple-negative breast cancer (TNBC)
      (P=0.007) and venous invasion (P=0.028). The in vitro cell experiment found that
      the MDA-MB-231 cell line, which is a TNBC cell line, highly expressed ANXA1.
      Using this cell line, the functional role of ANXA1 in breast cancer was revealed
      and the knockdown of ANXA1 by specific siRNA demonstrated a significant reduction
      in cellular invasion. Further experiments indicated that ANXA1 was induced by
      hypoxia with hypoxia-inducible factor-1alpha induction. These results suggested
      that ANXA1, which enhanced breast cancer invasion and metastasis under hypoxia,
      were significantly associated with the worst patient outcome. This is
      particularly noted in TNBC, the group of breast cancer with the worst outcome for
      which new therapeutic implications are required.

PMID- 25592492
TI  - The challenges of liver transplantation in children with primary sclerosing
      cholangitis.
AB  - Primary sclerosing cholangitis (PSC) in children can progress to end-stage liver
      disease requiring liver transplantation. PSC poses many challenges beginning with
      evaluation and classification of ductal involvement and overlap syndromes, few
      options for medical management and unique risks in the post-transplant period.
      The construct that PSC may be an autoimmune disease is based on positive
      autoantibodies, association with inflammatory bowel disease, linkage to HLA type
      and overlap/autoimmune sclerosing cholangitis; however, PSC is not responsive to
      standard immunosuppression. Study of PSC and post-transplant outcomes in children
      may provide a unique background in which to study this challenging disease. This
      is particularly intriguing in the subset of patients diagnosed in the first
      decade of life, suggesting a strong link to predisposing genetic susceptibility
      and immune dysregulation. Long-term, multicenter effort is likely to be the only
      mechanism to study this rare disease in children and to improve outcomes in the
      future. 

PMID- 25592493
TI  - A Review of Dietary Intake Studies in Maintenance Dialysis Patients.
AB  - Protein-energy wasting affects many maintenance dialysis patients (MDPs) and
      decreases survival. Suboptimal dietary energy intake (DEI) and dietary protein
      intake (DPI), secondary to reduced dietary intake (DI), are important risk
      factors in the development of protein-energy wasting. Multiple investigations of
      DEI and DPI in MDPs have occurred but few authors have synthesized these data. A
      comprehensive review of DI studies in MDPs was completed with the purpose of
      providing timely data on DI in MDPs until updated clinical practice guidelines
      for nutrition in nephrology care are published. A majority of DI investigations
      in MDPs confirm that DEI and DPI are below current nutrition guidelines. MDPs
      also have significantly lower DEI and DPI when compared with healthy controls.
      These findings inform the direction of further guidelines for nutrition in
      nephrology care as well as spark future research interests. 

PMID- 25592495
TI  - Science and satire.

PMID- 25592494
TI  - Histone deacetylase inhibitor sodium butyrate suppresses DNA double strand break
      repair induced by etoposide more effectively in MCF-7 cells than in HEK293 cells.
AB  - BACKGROUND: Histone deacetylase inhibitors (HDACi's) are emerging as promising
      anticancer drugs alone or in combination with chemotherapy or radiotherapy
      agents. Previous research suggests that HDACi's have a high degree of selectivity
      for killing cancer cells, but little is known regarding the impact of different
      cellular contexts on HDACi treatment. It is likely that the molecular mechanisms
      of HDACi's involve processes that depend on the chromatin template, such as DNA
      damage and repair. We sought to establish the connection between the HDACi sodium
      butyrate and DNA double-strand break (DSB) damage in human breast cancer MCF-7
      and non-cancerous human embryonic kidney293 (HEK293) cells. RESULTS: Sodium
      butyrate inhibited the proliferation of both HEK293 and MCF-7 cells in a dose-
      and time- dependent manner, but the effects on MCF-7 cells were more obvious.
      This differential effect on cell growth was not explained by differences in cell
      cycle arrest, as sodium butyrate caused an arrest in G1/G2 phase and a decrease
      in S phase for both cell lines. At high doses of sodium butyrate or in
      combination with etoposide, MCF-7 cells formed fewer colonies than HEK293 cells.
      Furthermore, sodium butyrate enhanced the formation of etoposide-induced gamma
      H2AX foci to a greater extent in MCF-7 than in HEK293 cells. The two cells also
      displayed differential patterns in the nuclear expression of DNA DSB repair
      proteins, which could, in part, explain the cytotoxic effects of sodium butyrate.
      CONCLUSIONS: These studies suggest that sodium butyrate treatment leads to a
      different degree of chromatin relaxation in HEK293 and cancerous MCF-7 cells,
      which results in differential sensitivity to the toxic effects of etoposide in
      controlling damaged DNA repair.

PMID- 25592496
TI  - Deep mysteries.

PMID- 25592497
TI  - Out of the bag.

PMID- 25592498
TI  - The focus on bibliometrics makes papers less useful.

PMID- 25592510
TI  - Political appointments spur concerns for Amazon.

PMID- 25592511
TI  - 'I can haz genomes': cats claw their way into genetics.

PMID- 25592512
TI  - First biosimilar drug set to enter US market.

PMID- 25592513
TI  - Blown-up brains reveal nanoscale details.

PMID- 25592514
TI  - Tropical paradise inspires virtual ecology lab.

PMID- 25592515
TI  - Mothballed NASA craft to launch.

PMID- 25592517
TI  - Agriculture: State-of-the-art soil.

PMID- 25592518
TI  - Microbiology: Here's looking at you, squid.

PMID- 25592519
TI  - Human adaptation: Manage climate-induced resettlement.

PMID- 25592522
TI  - Natural history: first museologist's legacy.

PMID- 25592523
TI  - Natural history: save Italy's museums.

PMID- 25592524
TI  - Pollinator assessment: IPBES responds on conflicts of interest.

PMID- 25592525
TI  - Conservation: Giant tortoises hatch on Galapagos island.

PMID- 25592526
TI  - Developing world: Use mentoring to fix science inequality.

PMID- 25592527
TI  - Alexander Grothendieck (1928-2014).

PMID- 25592528
TI  - Biomechanics: Boxed up and ready to go.

PMID- 25592529
TI  - Earth science: Mixing it up in the mantle.

PMID- 25592530
TI  - Physical chemistry: Hydrophobic interactions in context.

PMID- 25592531
TI  - Organic chemistry: One catalyst, two reactions.

PMID- 25592532
TI  - Frontiers in biology.

PMID- 25592533
TI  - From circuits to behaviour in the amygdala.
AB  - The amygdala has long been associated with emotion and motivation, playing an
      essential part in processing both fearful and rewarding environmental stimuli.
      How can a single structure be crucial for such different functions? With recent
      technological advances that allow for causal investigations of specific neural
      circuit elements, we can now begin to map the complex anatomical connections of
      the amygdala onto behavioural function. Understanding how the amygdala
      contributes to a wide array of behaviours requires the study of distinct amygdala
      circuits. 

PMID- 25592534
TI  - The biology of innate lymphoid cells.
AB  - The innate immune system is composed of a diverse array of evolutionarily ancient
      haematopoietic cell types, including dendritic cells, monocytes, macrophages and
      granulocytes. These cell populations collaborate with each other, with the
      adaptive immune system and with non-haematopoietic cells to promote immunity,
      inflammation and tissue repair. Innate lymphoid cells are the most recently
      identified constituents of the innate immune system and have been the focus of
      intense investigation over the past five years. We summarize the studies that
      formally identified innate lymphoid cells and highlight their emerging roles in
      controlling tissue homeostasis in the context of infection, chronic inflammation,
      metabolic disease and cancer. 

PMID- 25592535
TI  - Nutrient-sensing mechanisms and pathways.
AB  - The ability to sense and respond to fluctuations in environmental nutrient levels
      is a requisite for life. Nutrient scarcity is a selective pressure that has
      shaped the evolution of most cellular processes. Different pathways that detect
      intracellular and extracellular levels of sugars, amino acids, lipids and
      surrogate metabolites are integrated and coordinated at the organismal level
      through hormonal signals. During food abundance, nutrient-sensing pathways engage
      anabolism and storage, whereas scarcity triggers homeostatic mechanisms, such as
      the mobilization of internal stores through autophagy. Nutrient-sensing pathways
      are commonly deregulated in human metabolic diseases. 

PMID- 25592538
TI  - Impact jetting as the origin of chondrules.
AB  - Chondrules are the millimetre-scale, previously molten, spherules found in most
      meteorites. Before chondrules formed, large differentiating planetesimals had
      already accreted. Volatile-rich olivine reveals that chondrules formed in
      extremely solid-rich environments, more like impact plumes than the solar nebula.
      The unique chondrules in CB chondrites probably formed in a vapour-melt plume
      produced by a hypervelocity impact with an impact velocity greater than 10
      kilometres per second. An acceptable formation model for the overwhelming
      majority of chondrules, however, has not been established. Here we report that
      impacts can produce enough chondrules during the first five million years of
      planetary accretion to explain their observed abundance. Building on a previous
      study of impact jetting, we simulate protoplanetary impacts, finding that
      material is melted and ejected at high speed when the impact velocity exceeds 2.5
      kilometres per second. Using a Monte Carlo accretion code, we estimate the
      location, timing, sizes, and velocities of chondrule-forming impacts. Ejecta size
      estimates indicate that jetted melt will form millimetre-scale droplets. Our
      radiative transfer models show that these droplets experience the expected
      cooling rates of ten to a thousand kelvin per hour. An impact origin for
      chondrules implies that meteorites are a byproduct of planet formation rather
      than leftover building material.

PMID- 25592536
TI  - Necroptosis and its role in inflammation.
AB  - Regulated cell death has essential functions in development and in adult tissue
      homeostasis. Necroptosis is a newly discovered pathway of regulated necrosis that
      requires the proteins RIPK3 and MLKL and is induced by death receptors,
      interferons, toll-like receptors, intracellular RNA and DNA sensors, and probably
      other mediators. RIPK1 has important kinase-dependent and scaffolding functions
      that inhibit or trigger necroptosis and apoptosis. Mouse-model studies have
      revealed important functions for necroptosis in inflammation and suggested that
      it could be implicated in the pathogenesis of many human inflammatory diseases.
      We discuss the mechanisms regulating necroptosis and its potential role in
      inflammation and disease. 

PMID- 25592539
TI  - Direct observation of electron propagation and dielectric screening on the atomic
      length scale.
AB  - The propagation and transport of electrons in crystals is a fundamental process
      pertaining to the functioning of most electronic devices. Microscopic theories
      describe this phenomenon as being based on the motion of Bloch wave packets.
      These wave packets are superpositions of individual Bloch states with the group
      velocity determined by the dispersion of the electronic band structure near the
      central wavevector in momentum space. This concept has been verified
      experimentally in artificial superlattices by the observation of Bloch
      oscillations--periodic oscillations of electrons in real and momentum space. Here
      we present a direct observation of electron wave packet motion in a real-space
      and real-time experiment, on length and time scales shorter than the Bloch
      oscillation amplitude and period. We show that attosecond metrology (1 as = 10(
      18) seconds) now enables quantitative insight into weakly disturbed electron wave
      packet propagation on the atomic length scale without being hampered by
      scattering effects, which inevitably occur over macroscopic propagation length
      scales. We use sub-femtosecond (less than 10(-15) seconds) extreme-ultraviolet
      light pulses to launch photoelectron wave packets inside a tungsten crystal that
      is covered by magnesium films of varied, well-defined thicknesses of a few
      angstroms. Probing the moment of arrival of the wave packets at the surface with
      attosecond precision reveals free-electron-like, ballistic propagation behaviour
      inside the magnesium adlayer--constituting the semi-classical limit of Bloch wave
      packet motion. Real-time access to electron transport through atomic layers and
      interfaces promises unprecedented insight into phenomena that may enable the
      scaling of electronic and photonic circuits to atomic dimensions. In addition,
      this experiment allows us to determine the penetration depth of electrical fields
      at optical frequencies at solid interfaces on the atomic scale.

PMID- 25592537
TI  - Function and information content of DNA methylation.
AB  - Cytosine methylation is a DNA modification generally associated with
      transcriptional silencing. Factors that regulate methylation have been linked to
      human disease, yet how they contribute to malignances remains largely unknown.
      Genomic maps of DNA methylation have revealed unexpected dynamics at gene
      regulatory regions, including active demethylation by TET proteins at binding
      sites for transcription factors. These observations indicate that the underlying
      DNA sequence largely accounts for local patterns of methylation. As a result,
      this mark is highly informative when studying gene regulation in normal and
      diseased cells, and it can potentially function as a biomarker. Although these
      findings challenge the view that methylation is generally instructive for gene
      silencing, several open questions remain, including how methylation is targeted
      and recognized and in what context it affects genome readout. 

PMID- 25592540
TI  - Modulation of hydrophobic interactions by proximally immobilized ions.
AB  - The structure of water near non-polar molecular fragments or surfaces mediates
      the hydrophobic interactions that underlie a broad range of interfacial,
      colloidal and biophysical phenomena. Substantial progress over the past decade
      has improved our understanding of hydrophobic interactions in simple model
      systems, but most biologically and technologically relevant structures contain
      non-polar domains in close proximity to polar and charged functional groups.
      Theories and simulations exploring such nanometre-scale chemical heterogeneity
      find it can have an important effect, but the influence of this heterogeneity on
      hydrophobic interactions has not been tested experimentally. Here we report
      chemical force microscopy measurements on alkyl-functionalized surfaces that
      reveal a dramatic change in the surfaces' hydrophobic interaction strengths on co
      immobilization of amine or guanidine groups. Protonation of amine groups doubles
      the strength of hydrophobic interactions, and guanidinium groups eliminate
      measurable hydrophobic interactions in all pH ranges investigated. We see these
      divergent effects of proximally immobilized cations also in single-molecule
      measurements on conformationally stable beta-peptides with non-polar subunits
      located one nanometre from either amine- or guanidine-bearing subunits. Our
      results demonstrate the importance of nanometre-scale chemical heterogeneity,
      with hydrophobicity not an intrinsic property of any given non-polar domain but
      strongly modulated by functional groups located as far away as one nanometre. The
      judicious placing of charged groups near hydrophobic domains thus provides a
      strategy for tuning hydrophobic driving forces to optimize molecular recognition
      or self-assembly processes. 

PMID- 25592541
TI  - Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic
      alkylation.
AB  - The development of new reactions forming asymmetric carbon-carbon bonds has
      enabled chemists to synthesize a broad range of important carbon-containing
      molecules, including pharmaceutical agents, fragrances and polymers. Most
      strategies to obtain enantiomerically enriched molecules rely on either
      generating new stereogenic centres from prochiral substrates or resolving racemic
      mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric
      transformation--involves the transformation of a racemic starting material into a
      single enantiomer product, with greater than 50 per cent maximum yield. The use
      of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant)
      in palladium-catalysed asymmetric allylic alkylation reactions has proved to be
      extremely versatile in these processes. Conversely, the use of non-stabilized
      nucleophiles in such reactions is difficult and remains a key challenge. Here we
      report a copper-catalysed dynamic kinetic asymmetric transformation using racemic
      substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more
      than 25 orders of magnitude more basic than the nucleophiles that are typically
      used in such transformations. Organometallic reagents are generated in situ from
      alkenes by hydrometallation and give highly enantioenriched products under mild
      reaction conditions. The method is used to synthesize natural products that
      possess activity against tuberculosis and leprosy, and an inhibitor of para
      aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction
      proceeds through a rapidly isomerizing intermediate. We anticipate that this
      approach will be a valuable complement to existing asymmetric catalytic methods.

PMID- 25592544
TI  - Low-frequency repetitive transcranial magnetic stimulation on Parkinson motor
      function: a meta-analysis of randomised controlled trials.
AB  - OBJECTIVES: Previous studies have demonstrated inconsistent findings regarding
      the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS)
      in treating motor symptoms of Parkinson's disease (PD). Therefore, this meta
      analysis was conducted to assess the efficacy of low-frequency rTMS. METHODS: A
      comprehensive literature search (including PubMed, CCTR, Embase, Web of Science,
      CNKI, CBM-disc, NTIS,EAGLE, Clinical Trials, Current Controlled Trials,
      International Clinical Trials Registry) was conducted dating until June 2014. The
      key search terms ('Parkinson', 'PD', 'transcranial magnetic stimulation', 'TMS',
      'RTMS' and 'noninvasive brain stimulation') produced eight high-quality
      randomised controlled trials (RCT) of low-frequency rTMS versus sham stimulation.
      RESULTS: These eight studies, composed of 319 patients, were meta-analysed
      through assessment of the decreased Unified Parkinson's Disease Rating Scale
      (UPDRS part III) score. Pooling of the results from these RCTs yielded an effect
      size of -0.40 (95%CI=-0.73 to -0.06, p<0.05) in UPDRS part III, which indicated
      that low-frequency rTMS could have 5.05 (95%CI=-1.73 to -8.37) point decrease in
      UPDRS part III score than sham stimulation. DISCUSSION: Low-frequency rTMS had a
      significant effect on motor signs in PD. As the number of RCTs and PD patients
      included here was limited, further large-scale multi-center RCTs were required to
      validate our conclusions.

PMID- 25592542
TI  - The terrestrial uranium isotope cycle.
AB  - Changing conditions on the Earth's surface can have a remarkable influence on the
      composition of its overwhelmingly more massive interior. The global distribution
      of uranium is a notable example. In early Earth history, the continental crust
      was enriched in uranium. Yet after the initial rise in atmospheric oxygen, about
      2.4 billion years ago, the aqueous mobility of oxidized uranium resulted in its
      significant transport to the oceans and, ultimately, by means of subduction, back
      to the mantle. Here we explore the isotopic characteristics of this global
      uranium cycle. We show that the subducted flux of uranium is isotopically
      distinct, with high (238)U/(235)U ratios, as a result of alteration processes at
      the bottom of an oxic ocean. We also find that mid-ocean-ridge basalts (MORBs)
      have (238)U/(235)U ratios higher than does the bulk Earth, confirming the
      widespread pollution of the upper mantle with this recycled uranium. Although
      many ocean island basalts (OIBs) are argued to contain a recycled component,
      their uranium isotopic compositions do not differ from those of the bulk Earth.
      Because subducted uranium was probably isotopically unfractionated before full
      oceanic oxidation, about 600 million years ago, this observation reflects the
      greater antiquity of OIB sources. Elemental and isotope systematics of uranium in
      OIBs are strikingly consistent with previous OIB lead model ages, indicating that
      these mantle reservoirs formed between 2.4 and 1.8 billion years ago. In
      contrast, the uranium isotopic composition of MORB requires the convective
      stirring of recycled uranium throughout the upper mantle within the past 600
      million years. 

PMID- 25592546
TI  - Long-term toxicity study of rAd5-hTERTC27 in SD rats and Cynomolgus monkeys by
      intravenous injection.
AB  - rAd5-hTERTC27, a replication-defective adenovirus vector carrying hTERTC27, has
      been proposed for possible use against hepatocellular carcinoma (HCC). In this
      study, we investigated the long-term toxicity of rAd5-hTERTC27 in SD rats and
      Cynomolgus monkeys. rAd5-hTERTC27 was administered intravenously once a week for
      13 weeks followed by a one-month recovery period. As of 4 months, all animals
      displayed overall good health. Anti-adenoviral antibodies emerged in a dose
      independent manner. The levels of complement components, C3 and C4, in the rAd5
      hTERTC27 middle-dose and high-dose groups and C4 in the rAd5-EGFP group increased
      significantly after the 2nd treatment in monkeys. Slight-mild pathological
      changes of the liver occurred only in the rAd5-hTERTC27 high-dose group (2/16) in
      rats and not in any other group in either rats or monkeys. With the increase of
      the dose, the incidence of lymphocyte depletion in the spleen of rats and
      reactive hyperplasia of the splenic corpuscle in monkeys increased. However, the
      changes in the liver and spleen were reversible. Given the above data,
      intravenous administration of rAd5-hTERTC27 (up to 4*10(10)VP/kg in rats and
      0.9*10(10)VP/kg in monkeys) appears to be well-tolerated, providing support for
      its potentially safe use in clinical trials for the treatment of HCC.

PMID- 25592545
TI  - Production of cinnamic and p-hydroxycinnamic acid from sugar mixtures with
      engineered Escherichia coli.
AB  - BACKGROUND: The aromatic compounds cinnamic acid (CA) and p-hydroxycinnamic acid
      (pHCA) are used as flavoring agents as well as precursors of chemicals. These
      compounds are present in plants at low concentrations, therefore, complex
      purification processes are usually required to extract the product. An
      alternative production method for these aromatic acids is based on the use of
      microbial strains modified by metabolic engineering. These biotechnological
      processes are usually based on the use of simple sugars like glucose as a raw
      material. However, sustainable production processes should preferably be based on
      the use of waste material such as lignocellulosic hydrolysates. RESULTS: In this
      study, E. coli strains with active (W3110) and inactive phosphoenolpyruvate:sugar
      phosphotransferase system (PTS) (VH33) were engineered for CA and pHCA production
      by transforming them with plasmids expressing genes encoding
      phenylalanine/tyrosine ammonia lyase (PAL/TAL) enzymes from Rhodotorula glutinis
      or Arabidopsis thaliana as well as genes aroGfbr and tktA, encoding a feedback
      inhibition resistant version of 3-deoxy-D-arabino-heptulosonate 7-phosphate
      synthase and transketolase, respectively. The generated strains were evaluated in
      cultures with glucose, xylose or arabinose, as well as a simulated
      lignocellulosic hydrolysate containing a mixture of these three sugars plus
      acetate. Production of CA was detected in strains expressing PAL/TAL from A.
      thaliana, whereas both CA and pHCA accumulated in strains expressing the enzyme
      from R. glutinis. These experiments identified arabinose and W3110 expressing
      PAL/TAL from A. thaliana, aroGfbr and tktA as the carbon source/strain
      combination resulting in the best CA specific productivity and titer. To improve
      pHCA production, a mutant with inactive pheA gene was generated, causing an 8
      fold increase in the yield of this aromatic acid from the sugars in a simulated
      hydrolysate. CONCLUSIONS: In this study the quantitative contribution of active
      or inactive PTS as well as expression of PAL/TAL from R. glutinis or A. thaliana
      were determined for production performance of CA and pHCA when growing on carbon
      sources derived from lignocellulosic hydrolysates. These data will be a useful
      resource in efforts towards the development of sustainable technologies for the
      production of aromatic acids.

PMID- 25592548
TI  - Influence of insurance and marital status on outcomes of adolescents and young
      adults with acute lymphoblastic leukemia.
AB  - BACKGROUND: Although outcomes for adolescents and young adults (AYA) with acute
      lymphoblastic leukemia (ALL) are worse when treated according to adult rather
      than pediatric protocols, one criticism is that this may be due to the
      emancipation of young adults. METHODS: Using case listing session of
      Surveillance, Epidemiology, and End Results (SEER) 18 (1973-2010), we examined
      outcomes for AYA with ALL defined similar to Cancer and Leukemia Group B (CALGB)
      10,403 criteria (age 18-30) predicated on marital and insurance status as
      surrogates for emancipation (limiting analysis to 2007-2010). Analyses were
      conducted with SEER*Stat 8.1.2, Microsoft Excel 2007, and GraphPad Prism 6.
      Comparisons were made by the Fisher exact test and log rank test (Mantel-Cox);
      all P values were 2-sided. RESULTS: Although age (24 and younger vs. 25 and
      older) was predictive of median overall survival (OS) (not reached vs. 33; P =
      .0029) (3-year OS 66% vs. 49%), social factors were not. Three-year OS for
      insured versus uninsured patients was 61% versus 50%, and median OS was not
      reached versus 30 months (P = .2334). Three-year OS for single versus married
      patients was 62% versus 55%, with median OS not reached for both groups (P =
      .1084). CONCLUSION: Insurance status and marriage did not influence outcomes for
      AYA with ALL, suggesting that intrinsic differences in disease and disease
      specific therapies are more important than social issues.

PMID- 25592547
TI  - Genetics- and genomics-based interventions for nutritional enhancement of grain
      legume crops: status and outlook.
AB  - Meeting the food demands and ensuring nutritional security of the ever increasing
      global population in the face of degrading natural resource base and impending
      climate change is the biggest challenge of the twenty first century. The
      consequences of mineral/micronutrient deficiencies or the hidden hunger in the
      developing world are indeed alarming and need urgent attention. In addressing the
      problems associated with mineral/micronutrient deficiency, grain legumes as an
      integral component of the farming systems in the developing world have to play a
      crucial role. For resource-poor populations, a strategy based on selecting and/or
      developing grain legume cultivars with grains denser in micronutrients, by
      biofortification, seems the most appropriate and attractive approach to address
      the problem. This is evident from the on-going global research efforts on
      biofortification to provide nutrient-dense grains for use by the poorest of the
      poor in the developing countries. Towards this end, rapidly growing genomics
      technologies hold promise to hasten the progress of breeding nutritious legume
      crops. In conjunction with the myriad of expansions in genomics, advances in
      other 'omics' technologies particularly plant ionomics or ionome profiling open
      up novel opportunities to comprehensively examine the elemental composition and
      mineral networks of an organism in a rapid and cost-effective manner. These
      emerging technologies would effectively guide the scientific community to enrich
      the edible parts of grain legumes with bio-available minerals and
      enhancers/promoters. We believe that the application of these new-generation
      tools in turn would provide crop-based solutions to hidden hunger worldwide for
      achieving global nutritional security. 

PMID- 25592549
TI  - Site reactivity in the free radicals induced damage to leucine residues: a
      theoretical study.
AB  - Several recent computational studies have tried to explain the observed
      selectivity in radical damage to proteins. In this work we use Density Functional
      Theory and Transition State Theory including tunnelling corrections, reaction
      path degeneracy, the effect of diffusion, and the role of free radicals to get
      further insights into this important topic. The reaction between a leucine
      derivative and free radicals of biological significance, in aqueous and lipid
      media, has been investigated. Both thermochemical and kinetic analyses, in both
      hydrophilic and hydrophobic environments, have been carried out. DPPH, OOH,
      OOCH3, OOCH2Cl, OOCHCl2 and OOCHCH2 radicals do not react with the target
      molecule. The reactions are proposed to be kinetically controlled. The leucine
      gamma site was the most reactive for the reactions with N3, OOCCl3, OCH3, OCH2Cl,
      and OCHCl2 radicals, with rate constants equal to 1.97 * 10(5), 3.24 * 10(4),
      6.68 * 10(5), 5.98 * 10(6) and 8.87 * 10(8) M(-1) s(-1), respectively, in aqueous
      solution. The Cl, OH and OCCl3 radicals react with leucine at the beta, gamma,
      and delta positions at rates close to the diffusion limit with the alpha position
      which is the slowest path and the most thermodynamically favored. The presented
      results confirm that the Bell-Evans-Polanyi principle does not apply for the
      reactions between amino acid residues and free radicals. Regarding the influence
      of the environment on the reactivity of the studied series of free radicals
      towards leucine residues, it is concluded that hydrophilic media slightly lower
      the reactivity of the studied radicals, compared to hydrophobic ones, albeit the
      trends in reactivity are very similar. 

PMID- 25592550
TI  - Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend
      Particles.
AB  - PURPOSE: A key step of delivering extracellular agents to its intracellular
      target is to escape from endosomal/lysosomal compartments, while minimizing the
      release of digestive enzymes that may compromise cellular functions. In this
      study, we examined the intracellular distribution of both fluorecent cargoes and
      enzymes by a particle delivery platform made from the controlled blending of
      poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer.
      METHODS: We utilized both microscopic and biochemical methods to semi
      quantitatively assess how the composition of blend particles affects the level of
      endosomal escape of cargos of various sizes and enzymes into the cytosolic space.
      RESULTS: We demonstrated that these polymeric particles enabled the controlled
      delivery of cargos into the cytosolic space that was more dependent on the cargo
      size and less on the composition of blend particles. Blend particles did not
      induce the rupture of endosomal/lysosomal compartments and released less than 20%
      of endosomal/lysosomal enzymes. CONCLUSIONS: This study provides insight into
      understanding the efficacy and safety of a delivery system for intracellular
      delivery of biologics and drugs. Blend particles offer a potential platform to
      target intracellular compartments while potentially minimizing cellular toxicity.

PMID- 25592551
TI  - RGD Peptide-Pegylated PLLA Nanoparticles Containing Epirubicin Hydrochloride
      Exhibit Receptor-Dependent Tumor Trafficking In Vitro and In Vivo.
AB  - PURPOSE: A novel hydrophilic conjugate of arginine-glycine-aspartic acid (RGD)
      and polyethylene glycol (PEG), i.e., RGD-PEG Mw (M W = 300, 600, 1000 or 4000),
      was synthesized and employed in epirubicin (EPI) loaded poly L-lactic acid (PLLA)
      nanoparticles (NPs) to improve its tumor targeting effect. METHODS: In vitro
      studies were performed to assess EPI release from NPs in tumor-mimic acidic
      medium, cytotoxicity and cell cycle assay in HepG2 cells, and cellular uptake
      kinetics in four types of tumor cells including A375 cells (high integrin
      receptor expression), HeLa cells (low integrin receptor expression), and
      metabolic HepG2/SMMC7721 cells. In vivo pharmacodynamics (PD) and pharmacokinetic
      (PK) studies were determined in a murine ascites tumor model. RESULTS: Cellular
      uptake kinetics showed integrin receptor-dependent binding and internalization.
      In vitro release results showed that PLLA and PEG groups retarded EPI release
      from NPs and promoted drug release amount in acidic medium, which benefited in
      vivo trafficking to the acidic tumors. In vivo PD and PK studies revealed that
      RGD-PEG Mw (M W = 600 ~ 1000) improved tumor targeting capacity of NPs by ~2.4
      fold, compared to conventional EPI NPs. CONCLUSIONS: RGD-PEG Mw (M W = 600 ~
      1000) modified PLLA NPs provide a promising strategy to improve tumor selectivity
      in cancer treatment.

PMID- 25592552
TI  - Genetic variants are not associated with outcome in patients with coronary artery
      disease and left ventricular dysfunction: results of the Genetic Substudy of the
      Surgical Treatment for Ischemic Heart Failure (STICH) trials.
AB  - OBJECTIVES AND BACKGROUND: We evaluated the ability of 23 genetic variants to
      provide prognostic information in patients enrolled in the Genetic Substudy of
      the Surgical Treatment for Ischemic Heart Failure (STICH) trials. METHODS:
      Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with
      or without coronary artery bypass grafting (CABG). Those assigned to STICH
      Hypothesis 2 were randomized to CABG or CABG with left ventricular
      reconstruction. RESULTS: In patients assigned to STICH Hypothesis 2 (n = 714), no
      genetic variant met the prespecified Bonferroni-adjusted threshold for
      statistical significance (p < 0.002); however, several variants met nominal
      prognostic significance: variants in the beta2-adrenergic receptor gene (beta2-AR
      Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with
      an increased risk of a subject dying or being hospitalized for a cardiac problem
      (p = 0.027 and 0.031, respectively). These relationships remained nominally
      significant even after multivariable adjustment for prognostic clinical
      variables. However, none of the 23 genetic variants influenced all-cause
      mortality or the combination of death or cardiovascular hospitalization in the
      STICH Hypothesis 1 population (n = 532) by either univariate or multivariable
      analysis. CONCLUSION: We were unable to identify the predictive genotypes in
      optimally treated patients in these two ischemic heart failure populations.

PMID- 25592554
TI  - A 42-year-old patient presenting with femoral head migration after
      hemiarthroplasty performed 22 years earlier: a case report.
AB  - INTRODUCTION: Treatment of femoral neck fractures in young adults may require
      total hip arthroplasty or hip hemiarthroplasty using a bipolar cup. The latter
      can, however, result in migration of the femoral head and poor long-term results.
      CASE PRESENTATION: We report a case of femoral head migration after
      hemiarthroplasty performed for femoral neck fracture that had occurred 22 years
      earlier, when the patient (a Japanese man) was 20 years old. He experienced peri
      prosthetic fracture of the femur, subsequent migration of the prosthesis, and a
      massive bone defect of the pelvic side acetabular roof. After bone union of the
      femoral shaft fracture, the patient was referred to our hospital for
      reconstruction of the acetabular roof. Intra-operatively, we placed two
      alloimplants of bone from around the transplanted femoral head into the weight
      bearing region of the acetabular roof using an impaction bone graft method. We
      then implanted an acetabular roof reinforcement plate and a cemented polyethylene
      cup in the position of the original acetabular cup. Eighteen months post
      operatively, X-rays showed union of the transplanted bone. CONCLUSIONS: Treatment
      of femoral neck fractures in young adults is usually accomplished by
      osteosynthesis, but it may be complicated by femoral head avascular necrosis or
      by infection or osteomyelitis. In such cases, once an infection has subsided,
      either hip hemiarthroplasty using a bipolar cup or total hip arthroplasty may be
      required. However, if the acetabular side articular cartilage is damaged, a
      bipolar cup should not be used. Total hip arthroplasty should be performed to
      prevent migration of the implant.

PMID- 25592556
TI  - Acute kidney injury among adult patients with sepsis in a low-income country:
      clinical patterns and short-term outcomes.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication of sepsis. We
      determined the prevalence of AKI among adult patients with sepsis on the medical
      wards in a low-income country and described their clinical pattern and outcomes
      at discharge. METHODS: We conducted a cross-sectional study of sepsis-related AKI
      on the adult medical wards of Mulago National Referral Hospital between January
      and April 2013. All patients meeting the American College of Chest Physicians
      (ACP) sepsis criteria were recruited. Demographic, clinical, laboratory and
      ultrasonography data were recorded and all patients with AKI were followed up to
      a maximum of 2 weeks. Proportional analysis was carried out and odds ratios with
      95% confidence intervals were calculated in the bivariate analysis. RESULTS: Of
      387 patients recruited, 217 (55.6%) were male and the average age was 37 years
      (range18-90 years). The prevalence of sepsis-related AKI was 16.3%. Age >59 years
      (p = 0.023), a postural drop in systolic blood pressure of >9 mmHg (p = 0.015)
      and a white blood cell count >12,000 cells/mL (p = 0.003) were significantly
      associated with AKI. In-hospital mortality among patients with AKI was 21%
      (13/63). 59% (20/49) of patients who were discharged alive or were still on the
      wards after 2 weeks had persistent kidney injury. Acute Kidney Injury Network
      (AKIN) Stage 3 was significantly associated with persistence of kidney injury (p
      = 0.001). None of the patients requiring dialysis or ICU care received either
      because of limited access. CONCLUSIONS: The prevalence, morbidity and mortality
      due to AKI among sepsis patients in Uganda is very high and limited access to
      dialysis and ICU care is a major factor in poor outcomes for these patients.

PMID- 25592557
TI  - Intraoperative ultrasound imaging of coronary artery ostial stenosis.

PMID- 25592555
TI  - Fifteen years' experience of intestinal and multivisceral transplantation in the
      Nordic countries.
AB  - OBJECTIVE: Intestinal and multivisceral transplantation have gained acceptance as
      treatment modalities for patients with: intestinal failure and life-threatening
      complications of parenteral nutrition (PN), rare cases of vascular abdominal
      catastrophes and selected cases of low-grade neoplastic tumors such as
      neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The
      aim was to describe the survival and nutritional outcome in the transplanted
      Nordic patients and the complications attributed to this procedure. METHOD: The
      authors included all Nordic patients transplanted between January 1998 and
      December 2013. Information on patients transplanted outside the Nordic region was
      collected through questionnaires. RESULTS: A total of 34 patients received
      different types of intestinal allografts. Currently, there are two Nordic
      transplant centers (n = 29) performing these procedures (Gothenburg, Sweden n =
      24, Helsinki, Finland n = 5). The remaining five patients were transplanted in
      the USA (n = 3) and the UK (n = 2). Most patients were transplanted for life
      threatening failure of PN (70%) caused primarily by intestinal motility diseases
      (59%). Allograft rejection was the most common complication and occurred in 79%
      of the patients followed by post-transplantation lymphoproliferative disorders
      (21%) and graft-versus-host disease (18%). The 1- and 5-year survival was 79% and
      65% respectively for the whole cohort and nutritional autonomy was achieved in
      73% of the adults and 57% of the children at 1 year after transplantation.
      CONCLUSION: This collective Nordic experience confirms that intestinal
      transplantation is a complex procedure with many complications, yet with the
      possibility to provide long-term survival in selected conditions previously
      considered untreatable.

PMID- 25592553
TI  - Milk consumption during pregnancy increases birth weight, a risk factor for the
      development of diseases of civilization.
AB  - Antenatal dietary lifestyle intervention and nutrition during pregnancy and early
      postnatal life are important for appropriate lifelong metabolic programming.
      Epidemiological evidence underlines the crucial role of increased birth weight as
      a risk factor for the development of chronic diseases of civilization such as
      obesity, diabetes and cancer. Obstetricians and general practitioners usually
      recommend milk consumption during pregnancy as a nutrient enriched in valuable
      proteins and calcium for bone growth. However, milk is not just a simple
      nutrient, but has been recognized to function as an endocrine signaling system
      promoting anabolism and postnatal growth by activating the nutrient-sensitive
      kinase mTORC1. Moreover, pasteurized cow's milk transfers biologically active
      exosomal microRNAs into the systemic circulation of the milk consumer apparently
      affecting more than 11,000 human genes including the mTORC1-signaling pathway.
      This review provides literature evidence and evidence derived from translational
      research that milk consumption during pregnancy increases gestational, placental,
      fetal and birth weight. Increased birth weight is a risk factor for the
      development of diseases of civilization thus involving key disciplines of
      medicine. With regard to the presented evidence we suggest that dietary
      recommendations promoting milk consumption during pregnancy have to be re
      evaluated.

PMID- 25592558
TI  - Protecting the aorta during transcatheter aortic valve replacement: have we found
      the answer?

PMID- 25592559
TI  - Complications of intrathoracic lines placed during cardiac surgery.

PMID- 25592560
TI  - Thoracic endovascular aortic repair: satisfying early results but still a high
      midterm attrition rate.

PMID- 25592562
TI  - A twentieth anniversary tribute to PSB.
AB  - PSB brings together top researchers from around the world to exchange research
      results and address open issues in all aspects of computational biology. PSB 2015
      marks the twentieth anniversary of PSB. Reaching a milestone year is an
      accomplishment well worth celebrating. It is long enough to have seen big changes
      occur, but recent enough to be relevant for today. As PSB celebrates twenty years
      of service, we would like to take this opportunity to congratulate the PSB
      community for your success. We would also like the community to join us in a time
      of celebration and reflection on this accomplishment. 

PMID- 25592561
TI  - Outcome of localised blastemal-type Wilms tumour patients treated according to
      intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal
      Tumour Study Group (SIOP-RTSG).
AB  - Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk
      histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials
      of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study
      Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was
      intensified aiming to improve survival. Survival analysis of all unilateral BT-WT
      patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls
      (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients
      (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter
      Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III
      (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre
      operative chemotherapy and were diagnosed at an older median age compared to
      other WT patients. Patient characteristics did not differ substantially between
      SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival
      (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67%
      in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI:
      83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of
      relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age
      at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were
      prognostic variables for EFS (uni- and multivariate Cox regression analysis).
      Independent prognosticators for OS were age at diagnosis, tumour stage and volume
      (at surgery). The most significant survival benefit of intensified treatment, was
      observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)).
      BT-WT derived benefits from more intensive chemotherapy as reflected by a
      reduction in relapse risk. However, the benefit of the more intensive
      chemotherapy to improve OS was only observed in stage I BT-WTs, by adding
      doxorubicin.

PMID- 25592564
TI  - Cell Index Database (CELLX): a web tool for cancer precision medicine.
AB  - The Cell Index Database, (CELLX) (http://cellx.sourceforge.net) provides a
      computational framework for integrating expression, copy number variation,
      mutation, compound activity, and meta data from cancer cells. CELLX provides the
      computational biologist a quick way to perform routine analyses as well as the
      means to rapidly integrate data for offline analysis. Data is accessible through
      a web interface which utilizes R to generate plots and perform clustering,
      correlations, and statistical tests for associations within and between data
      types for ~20,000 samples from TCGA, CCLE, Sanger, GSK, GEO, GTEx, and other
      public sources. We show how CELLX supports precision oncology through indications
      discovery, biomarker evaluation, and cell line screening analysis. 

PMID- 25592565
TI  - Comparing nonparametric Bayesian tree priors for clonal reconstruction of tumors.
AB  - Statistical machine learning methods, especially nonparametric Bayesian methods,
      have become increasingly popular to infer clonal population structure of tumors.
      Here we describe the treeCRP, an extension of the Chinese restaurant process
      (CRP), a popular construction used in nonparametric mixture models, to infer the
      phylogeny and genotype of major subclonal lineages represented in the population
      of cancer cells. We also propose new split-merge updates tailored to the
      subclonal reconstruction problem that improve the mixing time of Markov chains.
      In comparisons with the tree-structured stick breaking prior used in PhyloSub, we
      demonstrate superior mixing and running time using the treeCRP with our new split
      merge procedures. We also show that given the same number of samples, TSSB and
      treeCRP have similar ability to recover the subclonal structure of a tumor... 

PMID- 25592566
TI  - Stepwise group sparse regression (SGSR): gene-set-based pharmacogenomic
      predictive models with stepwise selection of functional priors.
AB  - Complex mechanisms involving genomic aberrations in numerous proteins and
      pathways are believed to be a key cause of many diseases such as cancer. With
      recent advances in genomics, elucidating the molecular basis of cancer at a
      patient level is now feasible, and has led to personalized treatment strategies
      whereby a patient is treated according to his or her genomic profile. However,
      there is growing recognition that existing treatment modalities are overly
      simplistic, and do not fully account for the deep genomic complexity associated
      with sensitivity or resistance to cancer therapies. To overcome these
      limitations, large-scale pharmacogenomic screens of cancer cell lines--in
      conjunction with modern statistical learning approaches--have been used to
      explore the genetic underpinnings of drug response. While these analyses have
      demonstrated the ability to infer genetic predictors of compound sensitivity, to
      date most modeling approaches have been data-driven, i.e. they do not explicitly
      incorporate domain-specific knowledge (priors) in the process of learning a
      model. While a purely data-driven approach offers an unbiased perspective of the
      data--and may yield unexpected or novel insights--this strategy introduces
      challenges for both model interpretability and accuracy. In this study, we
      propose a novel prior-incorporated sparse regression model in which the choice of
      informative predictor sets is carried out by knowledge-driven priors (gene sets)
      in a stepwise fashion. Under regularization in a linear regression model, our
      algorithm is able to incorporate prior biological knowledge across the predictive
      variables thereby improving the interpretability of the final model with no loss-
      and often an improvement--in predictive performance. We evaluate the performance
      of our algorithm compared to well-known regularization methods such as LASSO,
      Ridge and Elastic net regression in the Cancer Cell Line Encyclopedia (CCLE) and
      Genomics of Drug Sensitivity in Cancer (Sanger) pharmacogenomics datasets,
      demonstrating that incorporation of the biological priors selected by our model
      confers improved predictability and interpretability, despite much fewer
      predictors, over existing state-of-the-art methods.

PMID- 25592567
TI  - Integrative genome-wide analysis of the determinants of RNA splicing in kidney
      renal clear cell carcinoma.
AB  - We present a genome-wide analysis of splicing patterns of 282 kidney renal clear
      cell carcinoma patients in which we integrate data from whole-exome sequencing of
      tumor and normal samples, RNA-seq and copy number variation. We proposed a
      scoring mechanism to compare splicing patterns in tumor samples to normal samples
      in order to rank and detect tumor-specific isoforms that have a potential for new
      biomarkers. We identified a subset of genes that show introns only observable in
      tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve
      our understanding of the underlying genetic mechanisms of splicing variation we
      performed a large-scale association analysis to find links between somatic or
      germline variants with alternative splicing events. We identified 915 cis- and
      trans-splicing quantitative trait loci (sQTL) associated with changes in splicing
      patterns. Some of these sQTL have previously been associated with being
      susceptibility loci for cancer and other diseases. Our analysis also allowed us
      to identify the function of several COSMIC variants showing significant
      association with changes in alternative splicing. This demonstrates the potential
      significance of variants affecting alternative splicing events and yields
      insights into the mechanisms related to an array of disease phenotypes. 

PMID- 25592568
TI  - An integrated framework for reporting clinically relevant biomarkers from paired
      tumor/normal genomic and transcriptomic sequencing data in support of clinical
      trials in personalized medicine.
AB  - The ability to rapidly sequence the tumor and germline DNA of an individual holds
      the eventual promise of revolutionizing our ability to match targeted therapies
      to tumors harboring the associated genetic biomarkers. Analyzing high throughput
      genomic data consisting of millions of base pairs and discovering alterations in
      clinically actionable genes in a structured and real time manner is at the crux
      of personalized testing. This requires a computational architecture that can
      monitor and track a system within a regulated environment as terabytes of data
      are reduced to a small number of therapeutically relevant variants, delivered as
      a diagnostic laboratory developed test. These high complexity assays require data
      structures that enable real-time and retrospective ad-hoc analysis, with a
      capability of updating to keep up with the rapidly changing genomic and
      therapeutic options, all under a regulated environment that is relevant under
      both CMS and FDA depending on application. We describe a flexible computational
      framework that uses a paired tumor/normal sample allowing for complete analysis
      and reporting in approximately 24 hours, providing identification of single
      nucleotide changes, small insertions and deletions, chromosomal rearrangements,
      gene fusions and gene expression with positive predictive values over 90%. In
      this paper we present the challenges in integrating clinical, genomic and
      annotation databases to provide interpreted draft reports which we utilize within
      ongoing clinical research protocols. We demonstrate the need to retire from
      existing performance measurements of accuracy and specificity and measure metrics
      that are meaningful to a genomic diagnostic environment. This paper presents a
      three-tier infrastructure that is currently being used to analyze an individual
      genome and provide available therapeutic options via a clinical report. Our
      framework utilizes a non-relational variant-centric database that is scaleable to
      a large amount of data and addresses the challenges and limitations of a
      relational database system. Our system is continuously monitored via multiple
      trackers each catering differently to the diversity of users involved in this
      process. These trackers designed in analytics web-app framework provide status
      updates for an individual sample accurate to a few minutes. In this paper, we
      also present our outcome delivery process that is designed and delivered adhering
      to the standards defined by various regulation agencies involved in clinical
      genomic testing. 

PMID- 25592569
TI  - Characteristics of drug combination therapy in oncology by analyzing clinical
      trial data on ClinicalTrials.gov.
AB  - Within the past few decades, drug combination therapy has been intensively
      studied in oncology and other complex disease areas, especially during the early
      drug discovery stage, as drug combinations have the potential to improve
      treatment response, minimize development of resistance or minimize adverse
      events. In the present, designing combination trials relies mainly on clinical
      and empirical experience. While empirical experience has indeed crafted
      efficacious combination therapy clinical trials (combination trials), however,
      garnering experience with patients can take a lifetime. The preliminary step to
      eliminating this barrier of time, then, is to understand the current state of
      combination trials. Thus, we present the first large-scale study of clinical
      trials (2008-2013) from ClinicalTrials.gov to compare combination trials to non
      combination trials, with a focus on oncology. In this work, we developed a
      classifier to identify combination trials and oncology trials through natural
      language processing techniques. After clustering trials, we categorized them
      based on selected characteristics and observed trends present. Among the
      characteristics studied were primary purpose, funding source, endpoint
      measurement, allocation, and trial phase. We observe a higher prevalence of
      combination therapy in oncology (25.6% use combination trials) in comparison to
      other disease trials (6.9%). However, surprisingly the prevalence of combinations
      does not increase over the years. In addition, the trials supported by the NIH
      are significantly more likely to use combinations of drugs than those supported
      by industry. Our preliminary study of current combination trials may facilitate
      future trial design and move more preclinical combination studies to the clinical
      trial stage. 

PMID- 25592573
TI  - Topological features in cancer gene expression data.
AB  - We present a new method for exploring cancer gene expression data based on tools
      from algebraic topology. Our method selects a small relevant subset from tens of
      thousands of genes while simultaneously identifying nontrivial higher order
      topological features, i.e., holes, in the data. We first circumvent the problem
      of high dimensionality by dualizing the data, i.e., by studying genes as points
      in the sample space. Then we select a small subset of the genes as landmarks to
      construct topological structures that capture persistent, i.e., topologically
      significant, features of the data set in its first homology group. Furthermore,
      we demonstrate that many members of these loops have been implicated for cancer
      biogenesis in scientific literature. We illustrate our method on five different
      data sets belonging to brain, breast, leukemia, and ovarian cancers. 

PMID- 25592572
TI  - Binning somatic mutations based on biological knowledge for predicting survival:
      an application in renal cell carcinoma.
AB  - Enormous efforts of whole exome and genome sequencing from hundreds to thousands
      of patients have provided the landscape of somatic genomic alterations in many
      cancer types to distinguish between driver mutations and passenger mutations.
      Driver mutations show strong associations with cancer clinical outcomes such as
      survival. However, due to the heterogeneity of tumors, somatic mutation profiles
      are exceptionally sparse whereas other types of genomic data such as miRNA or
      gene expression contain much more complete data for all genomic features with
      quantitative values measured in each patient. To overcome the extreme sparseness
      of somatic mutation profiles and allow for the discovery of combinations of
      somatic mutations that may predict cancer clinical outcomes, here we propose a
      new approach for binning somatic mutations based on existing biological
      knowledge. Through the analysis using renal cell carcinoma dataset from The
      Cancer Genome Atlas (TCGA), we identified combinations of somatic mutation burden
      based on pathways, protein families, evolutionary conversed regions, and
      regulatory regions associated with survival. Due to the nature of heterogeneity
      in cancer, using a binning strategy for somatic mutation profiles based on
      biological knowledge will be valuable for improved prognostic biomarkers and
      potentially for tailoring therapeutic strategies by identifying combinations of
      driver mutations. 

PMID- 25592571
TI  - Identifying mutation specific cancer pathways using a structurally resolved
      protein interaction network.
AB  - Here we present a method for extracting candidate cancer pathways from tumor
      'omics data while explicitly accounting for diverse consequences of mutations for
      protein interactions. Disease-causing mutations are frequently observed at either
      core or interface residues mediating protein interactions. Mutations at core
      residues frequently destabilize protein structure while mutations at interface
      residues can specifically affect the binding energies of protein-protein
      interactions. As a result, mutations in a protein may result in distinct
      interaction profiles and thus have different phenotypic consequences. We describe
      a protein structure-guided pipeline for extracting interacting protein sets
      specific to a particular mutation. Of 59 cancer genes with 3D co-complexed
      structures in the Protein Data Bank, 43 showed evidence of mutations with
      different functional consequences. Literature survey reciprocated functional
      predictions specific to distinct mutations on APC, ATRX, BRCA1, CBL and HRAS. Our
      analysis suggests that accounting for mutation-specific perturbations to cancer
      pathways will be essential for personalized cancer therapy. 

PMID- 25592574
TI  - Distant supervision for cancer pathway extraction from text.
AB  - Biological pathways are central to understanding complex diseases such as cancer.
      The majority of this knowledge is scattered in the vast and rapidly growing
      research literature. To automate knowledge extraction, machine learning
      approaches typically require annotated examples, which are expensive and time
      consuming to acquire. Recently, there has been increasing interest in leveraging
      databases for distant supervision in knowledge extraction, but existing
      applications focus almost exclusively on newswire domains. In this paper, we
      present the first attempt to formulate the distant supervision problem for
      pathway extraction and apply a state-of-the-art method to extracting pathway
      interactions from PubMed abstracts. Experiments show that distant supervision can
      effectively compensate for the lack of annotation, attaining an accuracy
      approaching supervised results. From 22 million PubMed abstracts, we extracted
      1.5 million pathway interactions at a precision of 25%. More than 10% of
      interactions are mentioned in the context of one or more cancer types, analysis
      of which yields interesting insights. 

PMID- 25592575
TI  - Unsupervised feature construction and knowledge extraction from genome-wide
      assays of breast cancer with denoising autoencoders.
AB  - Big data bring new opportunities for methods that efficiently summarize and
      automatically extract knowledge from such compendia. While both supervised
      learning algorithms and unsupervised clustering algorithms have been successfully
      applied to biological data, they are either dependent on known biology or limited
      to discerning the most significant signals in the data. Here we present denoising
      autoencoders (DAs), which employ a data-defined learning objective independent of
      known biology, as a method to identify and extract complex patterns from genomic
      data. We evaluate the performance of DAs by applying them to a large collection
      of breast cancer gene expression data. Results show that DAs successfully
      construct features that contain both clinical and molecular information. There
      are features that represent tumor or normal samples, estrogen receptor (ER)
      status, and molecular subtypes. Features constructed by the autoencoder
      generalize to an independent dataset collected using a distinct experimental
      platform. By integrating data from ENCODE for feature interpretation, we discover
      a feature representing ER status through association with key transcription
      factors in breast cancer. We also identify a feature highly predictive of patient
      survival and it is enriched by FOXM1 signaling pathway. The features constructed
      by DAs are often bimodally distributed with one peak near zero and another near
      one, which facilitates discretization. In summary, we demonstrate that DAs
      effectively extract key biological principles from gene expression data and
      summarize them into constructed features with convenient properties. 

PMID- 25592576
TI  - Automated gene expression pattern annotation in the mouse brain.
AB  - Brain tumor is a fatal central nervous system disease that occurs in around
      250,000 people each year globally and it is the second cause of cancer in
      children. It has been widely acknowledged that genetic factor is one of the
      significant risk factors for brain cancer. Thus, accurate descriptions of the
      locations of where the relative genes are active and how these genes express are
      critical for understanding the pathogenesis of brain tumor and for early
      detection. The Allen Developing Mouse Brain Atlas is a project on gene expression
      over the course of mouse brain development stages. Utilizing mouse models allows
      us to use a relatively homogeneous system to reveal the genetic risk factor of
      brain cancer. In the Allen atlas, about 435,000 high-resolution spatiotemporal in
      situ hybridization images have been generated for approximately 2,100 genes and
      currently the expression patterns over specific brain regions are manually
      annotated by experts, which does not scale with the continuously expanding
      collection of images. In this paper, we present an efficient computational
      approach to perform automated gene expression pattern annotation on brain images.
      First, the gene expression information in the brain images is captured by
      invariant features extracted from local image patches. Next, we adopt an
      augmented sparse coding method, called Stochastic Coordinate Coding, to construct
      high-level representations. Different pooling methods are then applied to
      generate gene-level features. To discriminate gene expression patterns at
      specific brain regions, we employ supervised learning methods to build accurate
      models for both binary-class and multi-class cases. Random undersampling and
      majority voting strategies are utilized to deal with the inherently imbalanced
      class distribution within each annotation task in order to further improve
      predictive performance. In addition, we propose a novel structure-based multi
      label classification approach, which makes use of label hierarchy based on brain
      ontology during model learning. Extensive experiments have been conducted on the
      atlas and results show that the proposed approach produces higher annotation
      accuracy than several baseline methods. Our approach is shown to be robust on
      both binary-class and multi-class tasks and even with a relatively low training
      ratio. Our results also show that the use of label hierarchy can significantly
      improve the annotation accuracy at all brain ontology levels. 

PMID- 25592578
TI  - Measures of exposure impact genetic association studies: an example in vitamin K
      levels and VKORC1.
AB  - Studies assessing the impact of gene-environment interactions on common human
      diseases and traits have been relatively few for many reasons. One often
      acknowledged reason is that it is difficult to accurately measure the environment
      or exposure. Indeed, most large-scale epidemiologic studies use questionnaires to
      assess and measure past and current exposure levels. While questionnaires may be
      cost-effective, the data may or may not accurately represent the exposure
      compared with more direct measurements (e.g., self-reported current smoking
      status versus direct measurement for cotinine levels). Much like phenotyping, the
      choice in how an exposure is measured may impact downstream tests of genetic
      association and gene-environment interaction studies. As a case study, we
      performed tests of association between five common VKORC1 SNPs and two different
      measurements of vitamin K levels, dietary (n=5,725) and serum (n=348), in the
      Third National Health and Nutrition Examination Studies (NHANES III). We did not
      replicate previously reported associations between VKORC1 and vitamin K levels
      using either measure. Furthermore, the suggestive associations and estimated
      genetic effect sizes identified in this study differed depending on the vitamin K
      measurement. This case study of VKORC1 and vitamin K levels serves as a
      cautionary example of the downstream consequences that the type of exposure
      measurement choices will have on genetic association and possibly gene
      environment studies. 

PMID- 25592579
TI  - A bipartite network approach to inferring interactions between environmental
      exposures and human diseases.
AB  - Environmental exposure is a key factor of understanding health and diseases.
      Beyond genetic propensities, many disorders are, in part, caused by human
      interaction with harmful substances in the water, the soil, or the air. Limited
      data is available on a disease or substance basis. However, we compile a global
      repository from literature surveys matching environmental chemical substances
      exposure with human disorders. We build a bipartite network linking 60 substances
      to over 150 disease phenotypes. We quantitatively and qualitatively analyze the
      network and its projections as simple networks. We identify mercury, lead and
      cadmium as associated with the largest number of disorders. Symmetrically, we
      show that breast cancer, harm to the fetus and non-Hodgkin's lymphoma are
      associated with the most environmental chemicals. We conduct statistical analysis
      of how vertices with similar characteristics form the network interactions. This
      dyadicity and heterophilicity measures the tendencies of vertices with similar
      properties to either connect to one-another. We study the dyadic distribution of
      the substance classes in the networks show that, for instance, tobacco smoke
      compounds, parabens and heavy metals tend to be connected, which hint at common
      disease causing factors, whereas fungicides and phytoestrogens do not. We build
      an exposure network at the systems level. The information gathered in this study
      is meant to be complementary to the genome and help us understand complex
      diseases, their commonalities, their causes, and how to prevent and treat them. 

PMID- 25592580
TI  - A screening-testing approach for detecting gene-environment interactions using
      sequential penalized and unpenalized multiple logistic regression.
AB  - Gene-environment (G * E) interactions are biologically important for a wide range
      of environmental exposures and clinical outcomes. Because of the large number of
      potential interactions in genomewide association data, the standard approach fits
      one model per G * E interaction with multiple hypothesis correction (MHC) used to
      control the type I error rate. Although sometimes effective, using one model per
      candidate G * E interaction test has two important limitations: low power due to
      MHC and omitted variable bias. To avoid the coefficient estimation bias
      associated with independent models, researchers have used penalized regression
      methods to jointly test all main effects and interactions in a single regression
      model. Although penalized regression supports joint analysis of all interactions,
      can be used with hierarchical constraints, and offers excellent predictive
      performance, it cannot assess the statistical significance of G * E interactions
      or compute meaningful estimates of effect size. To address the challenge of low
      power, researchers have separately explored screening-testing, or two-stage,
      methods in which the set of potential G * E interactions is first filtered and
      then tested for interactions with MHC only applied to the tests actually
      performed in the second stage. Although two-stage methods are statistically valid
      and effective at improving power, they still test multiple separate models and so
      are impacted by MHC and biased coefficient estimation. To remedy the challenges
      of both poor power and omitted variable bias encountered with traditional G * E
      interaction detection methods, we propose a novel approach that combines elements
      of screening-testing and hierarchical penalized regression. Specifically, our
      proposed method uses, in the first stage, an elastic net-penalized multiple
      logistic regression model to jointly estimate either the marginal association
      filter statistic or the gene-environment correlation filter statistic for all
      candidate genetic markers. In the second stage, a single multiple logistic
      regression model is used to jointly assess marginal terms and G * E interactions
      for all genetic markers that pass the first stage filter. A single likelihood
      ratio test is used to determine whether any of the interactions are statistically
      significant. We demonstrate the efficacy of our method relative to alternative G
      * E detection methods on a bladder cancer data set.

PMID- 25592581
TI  - Variable selection method for the identification of epistatic models.
AB  - Standard analysis methods for genome wide association studies (GWAS) are not
      robust to complex disease models, such as interactions between variables with
      small main effects. These types of effects likely contribute to the heritability
      of complex human traits. Machine learning methods that are capable of identifying
      interactions, such as Random Forests (RF), are an alternative analysis approach.
      One caveat to RF is that there is no standardized method of selecting variables
      so that false positives are reduced while retaining adequate power. To this end,
      we have developed a novel variable selection method called relative recurrency
      variable importance metric (r2VIM). This method incorporates recurrency and
      variance estimation to assist in optimal threshold selection. For this study, we
      specifically address how this method performs in data with almost completely
      epistatic effects (i.e. no marginal effects). Our results show that with
      appropriate parameter settings, r2VIM can identify interaction effects when the
      marginal effects are virtually nonexistent. It also outperforms logistic
      regression, which has essentially no power under this type of model when the
      number of potential features (genetic variants) is large. (All Supplementary Data
      can be found here: http://research.nhgri.nih.gov/manuscripts/Bailey
      Wilson/r2VIM_epi/). 

PMID- 25592582
TI  - Genome-wide genetic interaction analysis of glaucoma using expert knowledge
      derived from human phenotype networks.
AB  - The large volume of GWAS data poses great computational challenges for analyzing
      genetic interactions associated with common human diseases. We propose a
      computational framework for characterizing epistatic interactions among large
      sets of genetic attributes in GWAS data. We build the human phenotype network
      (HPN) and focus around a disease of interest. In this study, we use the GLAUGEN
      glaucoma GWAS dataset and apply the HPN as a biological knowledge-based filter to
      prioritize genetic variants. Then, we use the statistical epistasis network (SEN)
      to identify a significant connected network of pairwise epistatic interactions
      among the prioritized SNPs. These clearly highlight the complex genetic basis of
      glaucoma. Furthermore, we identify key SNPs by quantifying structural network
      characteristics. Through functional annotation of these key SNPs using Biofilter,
      a software accessing multiple publicly available human genetic data sources, we
      find supporting biomedical evidences linking glaucoma to an array of genetic
      diseases, proving our concept. We conclude by suggesting hypotheses for a better
      understanding of the disease. 

PMID- 25592583
TI  - Identification of gene-gene and gene-environment interactions within the
      fibrinogen gene cluster for fibrinogen levels in three ethnically diverse
      populations.
AB  - Elevated levels of plasma fibrinogen are associated with clot formation in the
      absence of inflammation or injury and is a biomarker for arterial clotting, the
      leading cause of cardiovascular disease. Fibrinogen levels are heritable with
      >50% attributed to genetic factors, however little is known about possible
      genetic modifiers that might explain the missing heritability. The fibrinogen
      gene cluster is comprised of three genes (FGA, FGB, and FGG) that make up the
      fibrinogen polypeptide essential for fibrinogen production in the blood. Given
      the known interaction with these genes, we tested 25 variants in the fibrinogen
      gene cluster for gene x gene and gene x environment interactions in 620 non
      Hispanic blacks, 1,385 non-Hispanic whites, and 664 Mexican Americans from a
      cross-sectional dataset enriched with environmental data, the Third National
      Health and Nutrition Examination Survey (NHANES III). Using a multiplicative
      approach, we added cross product terms (gene x gene or gene x environment) to a
      linear regression model and declared significance at p < 0.05. We identified 19
      unique gene x gene and 13 unique gene x environment interactions that impact
      fibrinogen levels in at least one population at p < 0.05. Over 90% of the gene x
      gene interactions identified include a variant in the rate-limiting gene, FGB
      that is essential for the formation of the fibrinogen polypeptide. We also
      detected gene x environment interactions with fibrinogen variants and sex,
      smoking, and body mass index. These findings highlight the potential for the
      discovery of genetic modifiers for complex phenotypes in multiple populations and
      give a better understanding of the interaction between genes and/or the
      environment for fibrinogen levels. The need for more powerful and robust methods
      to identify genetic modifiers is still warranted.

PMID- 25592584
TI  - Development of exposome correlation globes to map out environment-wide
      associations.
AB  - The environment plays a major role in influencing diseases and health. The
      phenomenon of environmental exposure is complex and humans are not exposed to one
      or a handful factors but potentially hundreds factors throughout their lives. The
      exposome, the totality of exposures encountered from birth, is hypothesized to
      consist of multiple inter-dependencies, or correlations, between individual
      exposures. These correlations may reflect how individuals are exposed. Currently,
      we lack methods to comprehensively identify robust and replicated correlations
      between environmental exposures of the exposome. Further, we have not mapped how
      exposures associated with disease identified by environment-wide association
      studies (EWAS) are correlated with other exposures. To this end, we implement
      methods to describe a first "exposome globe", a comprehensive display of
      replicated correlations between individual exposures of the exposome. First, we
      describe overall characteristics of the dense correlations between exposures,
      showing that we are able to replicate 2,656 correlations between individual
      exposures of 81,937 total considered (3%). We document the correlation within and
      between broad a priori defined categories of exposures (e.g., pollutants and
      nutrient exposures). We also demonstrate utility of the exposome globe to
      contextualize exposures found through two EWASs in type 2 diabetes and all-cause
      mortality, such as exposure clusters putatively related to smoking behaviors and
      persistent pollutant exposure. The exposome globe construct is a useful tool for
      the display and communication of the complex relationships between exposure
      factors and between exposure factors related to disease status. 

PMID- 25592586
TI  - iPINBPA: an integrative network-based functional module discovery tool for genome
      wide association studies.
AB  - We introduce the integrative protein-interaction-network-based pathway analysis
      (iPINBPA) for genome-wide association studies (GWAS), a method to identify and
      prioritize genetic associations by merging statistical evidence of association
      with physical evidence of interaction at the protein level. First, the strongest
      associations are used to weight all nodes in the PPI network using a guilt- by
      association approach. Second, the gene-wise converted p-values from a GWAS are
      integrated with node weights using the Liptak-Stouffer method. Finally, a greedy
      search is performed to find enriched modules, i.e., sub-networks with nodes that
      have low p-values and high weights. The performance of iPINBPA and other state-of
      the-art methods is assessed by computing the concentrated receiver operating
      characteristic (CROC) curves using two independent multiple sclerosis (MS) GWAS
      studies and one recent ImmunoChip study. Our results showed that iPINBPA
      identified sub-networks with smaller sizes and higher enrichments than other
      methods. iPINBPA offers a novel strategy to integrate topological connectivity
      and association signals from GWAS, making this an attractive tool to use in other
      large GWAS datasets. 

PMID- 25592585
TI  - Mitochondrial variation and the risk of age-related macular degeneration across
      diverse populations.
AB  - Substantial progress has been made in identifying susceptibility variants for age
      related macular degeneration (AMD). The majority of research to identify genetic
      variants associated with AMD has focused on nuclear genetic variation. While
      there is some evidence that mitochondrial genetic variation contributes to AMD
      susceptibility, to date, these studies have been limited to populations of
      European descent resulting in a lack of data in diverse populations. A major goal
      of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study
      is to describe the underlying genetic architecture of common, complex diseases
      across diverse populations. This present study sought to determine if
      mitochondrial genetic variation influences risk of AMD across diverse
      populations. We performed a genetic association study to investigate the
      contribution of mitochondrial DNA variation to AMD risk. We accessed samples from
      the National Health and Nutrition Examination Surveys, a U.S population-based,
      cross-sectional survey collected without regard to health status. AMD cases and
      controls were selected from the Third NHANES and NHANES 2007-2008 datasets which
      include non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. AMD
      cases were defined as those > 60 years of age with early/late AMD, as determined
      by fundus photography. Targeted genotyping was performed for 63 mitochondrial
      SNPs and participants were then classified into mitochondrial haplogroups. We
      used logistic regression assuming a dominant genetic model adjusting for age,
      sex, body mass index, and smoking status (ever vs. never). Regressions and meta
      analyses were performed for individual SNPs and mitochondrial haplogroups J, T,
      and U. We identified five SNPs associated with AMD in Mexican Americans at p <
      0.05, including three located in the control region (mt16111, mt16362, and
      mt16319), one in MT-RNR2 (mt1736), and one in MT-ND4 (mt12007). No mitochondrial
      variant or haplogroup was significantly associated in non-Hispanic blacks or non-
      Hispanic whites in the final meta-analysis. This study provides further evidence
      that mitochondrial variation plays a role in susceptibility to AMD and
      contributes to the knowledge of the genetic architecture of AMD in Mexican
      Americans. 

PMID- 25592587
TI  - Crowdsourcing and mining crowd data.
AB  - The following sections are included: Introduction, Session articles,
      Acknowledgements and References.

PMID- 25592588
TI  - Reputation-based collaborative network biology.
AB  - A pilot reputation-based collaborative network biology platform, Bionet, was
      developed for use in the sbv IMPROVER Network Verification Challenge to verify
      and enhance previously developed networks describing key aspects of lung biology.
      Bionet was successful in capturing a more comprehensive view of the biology
      associated with each network using the collective intelligence and knowledge of
      the crowd. One key learning point from the pilot was that using a standardized
      biological knowledge representation language such as BEL is critical to the
      success of a collaborative network biology platform. Overall, Bionet demonstrated
      that this approach to collaborative network biology is highly viable. Improving
      this platform for de novo creation of biological networks and network curation
      with the suggested enhancements for scalability will serve both academic and
      industry systems biology communities. 

PMID- 25592589
TI  - Microtask crowdsourcing for disease mention annotation in PubMed abstracts.
AB  - Identifying concepts and relationships in biomedical text enables knowledge to be
      applied in computational analyses. Many biological natural language processing
      (BioNLP) projects attempt to address this challenge, but the state of the art
      still leaves much room for improvement. Progress in BioNLP research depends on
      large, annotated corpora for evaluating information extraction systems and
      training machine learning models. Traditionally, such corpora are created by
      small numbers of expert annotators often working over extended periods of time.
      Recent studies have shown that workers on microtask crowdsourcing platforms such
      as Amazon's Mechanical Turk (AMT) can, in aggregate, generate high-quality
      annotations of biomedical text. Here, we investigated the use of the AMT in
      capturing disease mentions in PubMed abstracts. We used the NCBI Disease corpus
      as a gold standard for refining and benchmarking our crowdsourcing protocol.
      After several iterations, we arrived at a protocol that reproduced the
      annotations of the 593 documents in the 'training set' of this gold standard with
      an overall F measure of 0.872 (precision 0.862, recall 0.883). The output can
      also be tuned to optimize for precision (max = 0.984 when recall = 0.269) or
      recall (max = 0.980 when precision = 0.436). Each document was completed by 15
      workers, and their annotations were merged based on a simple voting method. In
      total 145 workers combined to complete all 593 documents in the span of 9 days at
      a cost of $.066 per abstract per worker. The quality of the annotations, as
      judged with the F measure, increases with the number of workers assigned to each
      task; however minimal performance gains were observed beyond 8 workers per task.
      These results add further evidence that microtask crowdsourcing can be a valuable
      tool for generating well-annotated corpora in BioNLP. Data produced for this
      analysis are available at
      http://figshare.com/articles/Disease_Mention_Annotation_with_Mechanical_Turk/1126
      02. 

PMID- 25592590
TI  - Crowdsourcing image annotation for nucleus detection and segmentation in
      computational pathology: evaluating experts, automated methods, and the crowd.
AB  - The development of tools in computational pathology to assist physicians and
      biomedical scientists in the diagnosis of disease requires access to high-quality
      annotated images for algorithm learning and evaluation. Generating high-quality
      expert-derived annotations is time-consuming and expensive. We explore the use of
      crowdsourcing for rapidly obtaining annotations for two core tasks in com-
      putational pathology: nucleus detection and nucleus segmentation. We designed and
      implemented crowdsourcing experiments using the CrowdFlower platform, which
      provides access to a large set of labor channel partners that accesses and
      manages millions of contributors worldwide. We obtained annotations from four
      types of annotators and compared concordance across these groups. We obtained:
      crowdsourced annotations for nucleus detection and segmentation on a total of 810
      images; annotations using automated methods on 810 images; annotations from
      research fellows for detection and segmentation on 477 and 455 images,
      respectively; and expert pathologist-derived annotations for detection and
      segmentation on 80 and 63 images, respectively. For the crowdsourced annotations,
      we evaluated performance across a range of contributor skill levels (1, 2, or 3).
      The crowdsourced annotations (4,860 images in total) were completed in only a
      fraction of the time and cost required for obtaining annotations using
      traditional methods. For the nucleus detection task, the research fellow-derived
      annotations showed the strongest concordance with the expert pathologist- derived
      annotations (F-M =93.68%), followed by the crowd-sourced contributor levels 1,2,
      and 3 and the automated method, which showed relatively similar performance (F-M
      = 87.84%, 88.49%, 87.26%, and 86.99%, respectively). For the nucleus segmentation
      task, the crowdsourced contributor level 3-derived annotations, research fellow
      derived annotations, and automated method showed the strongest concordance with
      the expert pathologist-derived annotations (F-M = 66.41%, 65.93%, and 65.36%,
      respectively), followed by the contributor levels 2 and 1 (60.89% and 60.87%,
      respectively). When the research fellows were used as a gold-standard for the
      segmentation task, all three con- tributor levels of the crowdsourced annotations
      significantly outperformed the automated method (F-M = 62.21%, 62.47%, and 65.15%
      vs. 51.92%). Aggregating multiple annotations from the crowd to obtain a
      consensus annotation resulted in the strongest performance for the crowd-sourced
      segmentation. For both detection and segmentation, crowd-sourced performance is
      strongest with small images (400 * 400 pixels) and degrades significantly with
      the use of larger images (600 * 600 and 800 * 800 pixels). We conclude that
      crowdsourcing to non-experts can be used for large-scale labeling microtasks in
      computational pathology and offers a new approach for the rapid generation of
      labeled images for algorithm development and evaluation. 

PMID- 25592592
TI  - Refining literature curated protein interactions using expert opinions.
AB  - The availability of high-quality physical interaction datasets is a prerequisite
      for system-level analysis of interactomes and supervised models to predict
      protein-protein interactions (PPIs). One source is literature-curated PPI
      databases in which pairwise associations of proteins published in the scientific
      literature are deposited. However, PPIs may not be clearly labelled as physical
      interactions affecting the quality of the entire dataset. In order to obtain a
      high-quality gold standard dataset for PPIs between human immunodeficiency virus
      (HIV-1) and its human host, we adopted a crowd-sourcing approach. We collected
      expert opinions and utilized an expectation-maximization based approach to
      estimate expert labeling quality. These estimates are used to infer the
      probability of a reported PPI actually being a direct physical interaction given
      the set of expert opinions. The effectiveness of our approach is demonstrated
      through synthetic data experiments and a high quality physical interaction
      network between HIV and human proteins is obtained. Since many literature-curated
      databases suffer from similar challenges, the framework described herein could be
      utilized in refining other databases. The curated data is available at
      http://www.cs.bilkent.edu.tr/~oznur.tastan/supp/psb2015/.

PMID- 25592591
TI  - Analyzing search behavior of healthcare professionals for drug safety
      surveillance.
AB  - Post-market drug safety surveillance is hugely important and is a significant
      challenge despite the existence of adverse event (AE) reporting systems. Here we
      describe a preliminary analysis of search logs from healthcare professionals as a
      source for detecting adverse drug events. We annotate search log query terms with
      biomedical terminologies for drugs and events, and then perform a statistical
      analysis to identify associations among drugs and events within search sessions.
      We evaluate our approach using two different types of reference standards
      consisting of known adverse drug events (ADEs) and negative controls. Our
      approach achieves a discrimination accuracy of 0.85 in terms of the area under
      the receiver operator curve (AUC) for the reference set of well-established ADEs
      and an AUC of 0.68 for the reference set of recently labeled ADEs. We also find
      that the majority of associations in the reference sets have support in the
      search log data. Despite these promising results additional research is required
      to better understand users' search behavior, biasing factors, and the overall
      utility of analyzing healthcare professional search logs for drug safety
      surveillance. 

PMID- 25592593
TI  - Crowdsourcing RNA structural alignments with an online computer game.
AB  - The annotation and classification of ncRNAs is essential to decipher molecular
      mechanisms of gene regulation in normal and disease states. A database such as
      Rfam maintains alignments, consensus secondary structures, and corresponding
      annotations for RNA families. Its primary purpose is the automated, accurate
      annotation of non-coding RNAs in genomic sequences. However, the alignment of
      RNAs is computationally challenging, and the data stored in this database are
      often subject to improvements. Here, we design and evaluate Ribo, a human
      computing game that aims to improve the accuracy of RNA alignments already stored
      in Rfam. We demonstrate the potential of our techniques and discuss the
      feasibility of large scale collaborative annotation and classification of RNA
      families. 

PMID- 25592594
TI  - Personalized medicine: from genotypes, molecular phenotypes and the quantified
      self, towards improved medicine.
AB  - Advances in molecular profiling and sensor technologies are expanding the scope
      of personalized medicine beyond genotypes, providing new opportunities for
      developing richer and more dynamic multi-scale models of individual health.
      Recent studies demonstrate the value of scoring high-dimensional microbiome,
      immune, and metabolic traits from individuals to inform personalized medicine.
      Efforts to integrate multiple dimensions of clinical and molecular data towards
      predictive multi-scale models of individual health and wellness are already
      underway. Improved methods for mining and discovery of clinical phenotypes from
      electronic medical records and technological developments in wearable sensor
      technologies present new opportunities for mapping and exploring the critical yet
      poorly characterized "phenome" and "envirome" dimensions of personalized
      medicine. There are ambitious new projects underway to collect multi-scale
      molecular, sensor, clinical, behavioral, and environmental data streams from
      large population cohorts longitudinally to enable more comprehensive and dynamic
      models of individual biology and personalized health. Personalized medicine
      stands to benefit from inclusion of rich new sources and dimensions of data.
      However, realizing these improvements in care relies upon novel informatics
      methodologies, tools, and systems to make full use of these data to advance both
      the science and translational applications of personalized medicine.

PMID- 25592595
TI  - Kleat: cleavage site analysis of transcriptomes.
AB  - In eukaryotic cells, alternative cleavage of 3' untranslated regions (UTRs) can
      affect transcript stability, transport and translation. For polyadenylated
      (poly(A)) transcripts, cleavage sites can be characterized with short-read
      sequencing using specialized library construction methods. However, for large
      scale cohort studies as well as for clinical sequencing applications, it is
      desirable to characterize such events using RNA-seq data, as the latter are
      already widely applied to identify other relevant information, such as mutations,
      alternative splicing and chimeric transcripts. Here we describe KLEAT, an
      analysis tool that uses de novo assembly of RNA-seq data to characterize cleavage
      sites on 3' UTRs. We demonstrate the performance of KLEAT on three cell line RNA
      seq libraries constructed and sequenced by the ENCODE project, and assembled
      using Trans-ABySS. Validating the KLEAT predictions with matched ENCODE RNA-seq
      and RNA-PET libraries, we show that the tool has over 90% positive predictive
      value when there are at least three RNA-seq reads supporting a poly(A) tail and
      requiring at least three RNA-PET reads mapping within 100 nucleotides as
      validation. We also compare the performance of KLEAT with other popular RNA-seq
      analysis pipelines that reconstruct 3' UTR ends, and show that it performs
      favourably, based on an ROC-like curve. 

PMID- 25592596
TI  - Causal inference in biology networks with integrated belief propagation.
AB  - Inferring causal relationships among molecular and higher order phenotypes is a
      critical step in elucidating the complexity of living systems. Here we propose a
      novel method for inferring causality that is no longer constrained by the
      conditional dependency arguments that limit the ability of statistical causal
      inference methods to resolve causal relationships within sets of graphical models
      that are Markov equivalent. Our method utilizes Bayesian belief propagation to
      infer the responses of perturbation events on molecular traits given a
      hypothesized graph structure. A distance measure between the inferred response
      distribution and the observed data is defined to assess the 'fitness' of the
      hypothesized causal relationships. To test our algorithm, we infer causal
      relationships within equivalence classes of gene networks in which the form of
      the functional interactions that are possible are assumed to be nonlinear, given
      synthetic microarray and RNA sequencing data. We also apply our method to infer
      causality in real metabolic network with v-structure and feedback loop. We show
      that our method can recapitulate the causal structure and recover the feedback
      loop only from steady-state data which conventional method cannot. 

PMID- 25592597
TI  - Machine learning from concept to clinic: reliable detection of BRAF V600E DNA
      mutations in thyroid nodules using high-dimensional RNA expression data.
AB  - The promise of personalized medicine will require rigorously validated molecular
      diagnostics developed on minimally invasive, clinically relevant samples.
      Measurement of DNA mutations is increasingly common in clinical settings but only
      higher-prevalence mutations are cost-effective. Patients with rare variants are
      at best ignored or, at worst, misdiagnosed. Mutations result in downstream
      impacts on transcription, offering the possibility of broader diagnosis for
      patients with rare variants causing similar downstream changes. Use of such
      signatures in clinical settings is rare as these algorithms are difficult to
      validate for commercial use. Validation on a test set (against a clinical gold
      standard) is necessary but not sufficient: accuracy must be maintained amidst
      interfering substances, across reagent lots and across operators. Here we report
      the development, clinical validation, and diagnostic accuracy of a pre-operative
      molecular test (Afirma BRAF) to identify BRAF V600E mutations using mRNA
      expression in thyroid fine needle aspirate biopsies (FNABs). FNABs were obtained
      prospectively from 716 nodules and more than 3,000 features measured using
      microarrays. BRAF V600E labels for training (n=181) and independent test (n=535)
      sets were established using a sensitive quantitative PCR (qPCR) assay. The
      resulting 128-gene linear support vector machine was compared to qPCR in the
      independent test set. Clinical sensitivity and specificity for malignancy were
      evaluated in a subset of test set samples (n=213) with expert-derived
      histopathology. We observed high positive- (PPA, 90.4%) and negative (NPA, 99.0%)
      percent agreement with qPCR on the test set. Clinical sensitivity for malignancy
      was 43.8% (consistent with published prevalence of BRAF V600E in this neoplasm)
      and specificity was 100%, identical to qPCR on the same samples. Classification
      was accurate in up to 60% blood. A double-mutant still resulting in the V600E
      amino acid change was negative by qPCR but correctly positive by Afirma BRAF. Non
      diagnostic rates were lower (7.6%) for Afirma BRAF than for qPCR (24.5%), a
      further advantage of using RNA in small sample biopsies. Afirma BRAF accurately
      determined the presence or absence of the BRAF V600E DNA mutation in FNABs, a
      collection method directly relevant to solid tumor assessment, with performance
      equal to that of an established, highly sensitive DNA-based assay and with a
      lower non-diagnostic rate. This is the first such test in thyroid cancer to
      undergo sufficient analytical and clinical validation for real-world use in a
      personalized medicine context to frame individual patient risk and inform
      surgical choice. 

PMID- 25592599
TI  - Drug-induced mRNA signatures are enriched for the minority of genes that are
      highly heritable.
AB  - The blood gene expression signatures are used as biomarkers for immunological and
      non- immunological diseases. Therefore, it is important to understand the
      variation in blood gene expression patterns and the factors (heritable/non
      heritable) that underlie this variation. In this paper, we study the relationship
      between drug effects on the one hand, and heritable and non-heritable factors
      influencing gene expression on the other. Understanding of this relationship can
      help select appropriate targets for drugs aimed at reverting disease phenotypes
      to healthy states. In order to estimate heritable and non-heritable effects on
      gene expression, we use Twin-ACE model on a gene expression dataset MuTHER,
      measured in blood samples from monozygotic and dizygotic twins. In order to
      associate gene expression with drug effects, we use CMap database. We show that,
      even though the expressions of most genes are driven by non-heritable factors,
      drugs are more likely to influence expression of genes, driven by heritable
      rather than non-heritable factors. We further study this finding in the context
      of a gene regulatory network. We investigate the relationship between the drug
      effects on gene expression and propagation of heritable and non-heritable factors
      through regulatory networks. We find that the decisive factor in determining
      whether a gene will be influenced by a drug is the flow of heritable effects
      supplied to the gene through regulatory network. 

PMID- 25592598
TI  - A systematic assessment of linking gene expression with genetic variants for
      prioritizing candidate targets.
AB  - Gene expression and disease-associated variants are often used to prioritize
      candidate genes for target validation. However, the success of these gene
      features alone or in combination in the discovery of therapeutic targets is
      uncertain. Here we evaluated the effectiveness of the differential expression
      (DE), the disease-associated single nucleotide polymorphisms (SNPs) and the
      combination of the two in recovering and predicting known therapeutic targets
      across 56 human diseases. We demonstrate that the performance of each feature
      varies across diseases and generally the features have more recovery power than
      predictive power. The combination of the two features, however, has significantly
      higher predictive power than each feature alone. Our study provides a systematic
      evaluation of two common gene features, DE and SNPs, for prioritization of
      candidate targets and identified an improved predictive power of coupling these
      two features. 

PMID- 25592600
TI  - An integrative pipeline for multi-modal discovery of disease relationships.
AB  - In the past decade there has been an explosion in genetic research that has
      resulted in the generation of enormous quantities of disease-related data. In the
      current study, we have compiled disease risk gene variant information and
      Electronic Medical Record (EMR) classification codes from various repositories
      for 305 diseases. Using such data, we developed a pipeline to test for clinical
      prevalence, gene-variant overlap, and literature presence for all 46,360 unique
      diseases pairs. To determine whether disease pairs were enriched we
      systematically employed both Fishers' Exact (medical and literature) and Term
      Frequency-Inverse Document Frequency (genetics) methodologies to test for
      enrichment, defining statistical significance at a Bonferonni adjusted threshold
      of (p < 1 * 10(-6)) and weighted q < 0.05 accordingly. We hypothesize that
      disease pairs that are statistically enriched in medical and genetic spheres, but
      not so in the literature have the potential to reveal non-obvious connections
      between clinically disparate phenotypes. Using this pipeline, we identified 2,316
      disease pairs that were significantly enriched within an EMR and 213 enriched
      genetically. Of these, 65 disease pairs were statistically enriched in both, 19
      of which are believed to be novel. These identified non-obvious relationships
      between disease pairs are suggestive of a shared underlying etiology with
      clinical presentation. Further investigation of uncovered disease-pair
      relationships has the potential to provide insights into the architecture of
      complex diseases, and update existing knowledge of risk factors.

PMID- 25592601
TI  - Peax: interactive visual analysis and exploration of complex clinical phenotype
      and gene expression association.
AB  - Increasing availability of high-dimensional clinical data, which improves the
      ability to define more specific phenotypes, as well as molecular data, which can
      elucidate disease mechanisms, is a driving force and at the same time a major
      challenge for translational and personalized medicine. Successful research in
      this field requires an approach that ties together specific disease and health
      expertise with understanding of molecular data through statistical methods. We
      present PEAX (Phenotype-Expression Association eXplorer), built upon open-source
      software, which integrates visual phenotype model definition with statistical
      testing of expression data presented concurrently in a web-browser. The
      integration of data and analysis tasks in a single tool allows clinical domain
      experts to obtain new insights directly through exploration of relationships
      between multivariate phenotype models and gene expression data, showing the
      effects of model definition and modification while also exploiting potential
      meaningful associations between phenotype and miRNA-mRNA regulatory
      relationships. We combine the web visualization capabilities of Shiny and D3 with
      the power and speed of R for backend statistical analysis, in order to abstract
      the scripting required for repetitive analysis of sub-phenotype association. We
      describe the motivation for PEAX, demonstrate its utility through a use case
      involving heart failure research, and discuss computational challenges and
      observations. We show that our visual web-based representations are well-suited
      for rapid exploration of phenotype and gene expression association, facilitating
      insight and discovery by domain experts. 

PMID- 25592603
TI  - Meta-analysis of differential gene co-expression: application to lupus.
AB  - We present a novel statistical framework for meta-analysis of differential gene
      co-expression. In contrast to standard methods, which identify genes that are
      over or under expressed in disease vs controls, differential co-expression
      identifies gene pairs with correlated expression profiles specific to one state.
      We apply our differential co-expression meta-analysis method to identify genes
      specifically mis-expressed in blood-derived cells of systemic lupus erythematosus
      (SLE) patients. The resulting network is strongly enriched for genes genetically
      associated with SLE, and effectively identifies gene modules known to play
      important roles in SLE etiology, such as increased type 1 interferon response and
      response to wounding. Our results also strongly support previous preliminary
      studies suggesting a role for dysregulation of neutrophil extracellular trap
      formation in SLE. Strikingly, two of the gene modules we identify contain SLE
      associated transcription factors that have binding sites significantly enriched
      in the promoter regions of their respective gene modules, suggesting a possible
      mechanism underlying the mis-expression of the modules. Thus, our general method
      is capable of identifying specific dysregulated gene expression programs, as
      opposed to large global responses. We anticipate that methods such as ours will
      be more and more useful as gene expression monitoring becomes increasingly common
      in clinical settings. 

PMID- 25592602
TI  - T-ReCS: stable selection of dynamically formed groups of features with
      application to prediction of clinical outcomes.
AB  - Feature selection is used extensively in biomedical research for biomarker
      identification and patient classification, both of which are essential steps in
      developing personalized medicine strategies. However, the structured nature of
      the biological datasets and high correlation of variables frequently yield
      multiple equally optimal signatures, thus making traditional feature selection
      methods unstable. Features selected based on one cohort of patients, may not work
      as well in another cohort. In addition, biologically important features may be
      missed due to selection of other co-clustered features We propose a new method,
      Tree-guided Recursive Cluster Selection (T-ReCS), for efficient selection of
      grouped features. T-ReCS significantly improves predictive stability while
      maintains the same level of accuracy. T-ReCS does not require an a priori
      knowledge of the clusters like group-lasso and also can handle "orphan" features
      (not belonging to a cluster). T-ReCS can be used with categorical or survival
      target variables. Tested on simulated and real expression data from breast cancer
      and lung diseases and survival data, T-ReCS selected stable cluster features
      without significant loss in classification accuracy. 

PMID- 25592605
TI  - Bayclone: Bayesian nonparametric inference of tumor subclones using NGS data.
AB  - In this paper, we present a novel feature allocation model to describe tumor
      heterogeneity (TH) using next-generation sequencing (NGS) data. Taking a Bayesian
      approach, we extend the Indian buffet process (IBP) to define a class of
      nonparametric models, the categorical IBP (cIBP). A cIBP takes categorical values
      to denote homozygous or heterozygous genotypes at each SNV. We define a subclone
      as a vector of these categorical values, each corresponding to an SNV. Instead of
      partitioning somatic mutations into non-overlapping clusters with similar
      cellular prevalences, we took a different approach using feature allocation.
      Importantly, we do not assume somatic mutations with similar cellular prevalence
      must be from the same subclone and allow overlapping mutations shared across
      subclones. We argue that this is closer to the underlying theory of phylogenetic
      clonal expansion, as somatic mutations occurred in parent subclones should be
      shared across the parent and child subclones. Bayesian inference yields posterior
      probabilities of the number, genotypes, and proportions of subclones in a tumor
      sample, thereby providing point estimates as well as variabilities of the
      estimates for each subclone. We report results on both simulated and real data.
      BayClone is available at http://health.bsd.uchicago.edu/yji/soft.html. 

PMID- 25592606
TI  - Human evolutionary genomics and the search for the genes that made us human.

PMID- 25592604
TI  - Melancholic depression prediction by identifying representative features in
      metabolic and microarray profiles with missing values.
AB  - Recent studies have revealed that melancholic depression, one major subtype of
      depression, is closely associated with the concentration of some metabolites and
      biological functions of certain genes and pathways. Meanwhile, recent advances in
      biotechnologies have allowed us to collect a large amount of genomic data, e.g.,
      metabolites and microarray gene expression. With such a huge amount of
      information available, one approach that can give us new insights into the
      understanding of the fundamental biology underlying melancholic depression is to
      build disease status prediction models using classification or regression
      methods. However, the existence of strong empirical correlations, e.g., those
      exhibited by genes sharing the same biological pathway in microarray profiles,
      tremendously limits the performance of these methods. Furthermore, the occurrence
      of missing values which are ubiquitous in biomedical applications further
      complicates the problem. In this paper, we hypothesize that the problem of
      missing values might in some way benefit from the correlation between the
      variables and propose a method to learn a compressed set of representative
      features through an adapted version of sparse coding which is capable of
      identifying correlated variables and addressing the issue of missing values
      simultaneously. An efficient algorithm is also developed to solve the proposed
      formulation. We apply the proposed method on metabolic and microarray profiles
      collected from a group of subjects consisting of both patients with melancholic
      depression and healthy controls. Results show that the proposed method can not
      only produce meaningful clusters of variables but also generate a set of
      representative features that achieve superior classification performance over
      those generated by traditional clustering and data imputation techniques. In
      particular, on both datasets, we found that in comparison with the competing
      algorithms, the representative features learned by the proposed method give rise
      to significantly improved sensitivity scores, suggesting that the learned
      features allow prediction with high accuracy of disease status in those who are
      diagnosed with melancholic depression. To our best knowledge, this is the first
      work that applies sparse coding to deal with high feature correlations and
      missing values, which are common challenges in many biomedical applications. The
      proposed method can be readily adapted to other biomedical applications involving
      incomplete and high-dimensional data. 

PMID- 25592607
TI  - Discovery informatics in biological and biomedical sciences: research challenges
      and opportunities.
AB  - New discoveries in biological, biomedical and health sciences are increasingly
      being driven by our ability to acquire, share, integrate and analyze, and
      construct and simulate predictive models of biological systems. While much
      attention has focused on automating routine aspects of management and analysis of
      "big data", realizing the full potential of "big data" to accelerate discovery
      calls for automating many other aspects of the scientific process that have so
      far largely resisted automation: identifying gaps in the current state of
      knowledge; generating and prioritizing questions; designing studies; designing,
      prioritizing, planning, and executing experiments; interpreting results; forming
      hypotheses; drawing conclusions; replicating studies; validating claims;
      documenting studies; communicating results; reviewing results; and integrating
      results into the larger body of knowledge in a discipline. Against this
      background, the PSB workshop on Discovery Informatics in Biological and
      Biomedical Sciences explores the opportunities and challenges of automating
      discovery or assisting humans in discovery through advances (i) Understanding,
      formalization, and information processing accounts of, the entire scientific
      process; (ii) Design, development, and evaluation of the computational artifacts
      (representations, processes) that embody such understanding; and (iii)
      Application of the resulting artifacts and systems to advance science (by
      augmenting individual or collective human efforts, or by fully automating
      science).

PMID- 25592608
TI  - Inviting the public: the impact on informatics arising from emerging global
      health research paradigms.
AB  - This workshop will focus on disruptive processes impacting research arising from
      the increasing ability of individuals to create, curate and share data with
      scientists. Encompassing processes from funding research to providing samples to
      creating algorithms, including the public will require new approaches even as it
      opens up new possibilities. We will hear from a few researchers at the forefront
      of these disruptive processes, followed by a moderated discussion with the
      audience about these topics. 

PMID- 25592609
TI  - Training the next generation of quantitative biologists in the era of big data.
AB  - The following sections are included: Workshop Focus, Workshop Contributions and
      References. 

PMID- 25592611
TI  - Timing of neurological improvement after acute ischemic stroke and functional
      outcome.
AB  - BACKGROUND: The time of neurological improvement (TNI) after acute ischemic
      stroke may have a predictive value. METHODS: We evaluated 410 consecutive
      patients who were admitted within 12 hours of stroke onset. The National
      Institutes of Health Stroke Scale (NIHSS) was measured on admission and at 1, 3,
      7, and 14 days. Neurological improvement was defined as an improvement in the
      NIHSS score by >=2 points (NI2) or >=4 points (NI4) or an NIHSS score of 0.
      Patients with a Modified Rankin scale (mRS) score of <=2 were considered to have
      a good outcome. RESULTS: Patients with earlier TNIs had a lower 3-month mRS score
      and a higher probability for a good outcome. In the binary and ordinal regression
      analyses, age, NIHSS score, atrial fibrillation and TNI were independently
      associated with a good outcome. Receiver operating characteristic curve analyses
      demonstrated that TNI2 had higher sensitivity and lower specificity than TNI4.
      The best threshold for predicting outcome was day 3 for TNI2 and day 14 for TNI4.
      CONCLUSIONS: These results suggest that TNI is independently associated with
      functional outcome at 90 days. TNI2 may be more useful than TNI4 for early
      prediction of stroke outcome.

PMID- 25592612
TI  - Serum HBsAg and HBeAg levels are associated with liver pathological stages in the
      immune clearance phase of hepatitis B virus chronic infection.
AB  - The association between hepatitis B surface antigen (HBsAg) and hepatitis B 'e'
      antigen (HBeAg) levels and liver inflammation and fibrosis in patients with
      chronic hepatitis B (CHB) in the immune clearance (IC) remains elusive. The aim
      of the present study was to investigate whether HBsAg and HBeAg levels were
      associated with liver inflammation and fibrosis in CHB patients during the IC
      phase. Kendall's rank correlation analysis and receiver operating characteristic
      curves were used to determine the correlation between HBsAg, HBeAg and liver
      pathological stages. Multivariate analysis by forward logistic regression was
      used to analyze significant predictors of cirrhosis. A liver pathology-predicting
      model (IC model), which used routinely assessed markers in combination with HBsAg
      and HBeAg levels, was constructed. There were significantly positive correlations
      between the HBsAg and HBeAg levels (gamma=0.317, P<0.001), and between the HBsAg
      and HBV-DNA levels (gamma=0.489, P<0.001). However, there was no correlation
      between the HBsAg and alanine aminotransferase levels. HBsAg and HBeAg levels
      differed significantly at various liver pathological stages and declined
      progressively in advanced liver pathological stages. Multivariate logistic
      regression analysis showed that age, HBsAg and HBeAg levels as well as the
      international normalized ratio (INR) were independent predictors of liver
      fibrosis during the IC phase. The IC model had a specificity and sensitivity of
      88.64 and 78.24%, respectively, a positive predictive value of 48.15% and
      negative predictive value of 96.79%. In conclusion, HBsAg and HBeAg levels were
      negatively and indirectly correlated with liver inflammation and fibrosis in CHB
      patients in the IC phase. The IC model reliably predicted the probability of
      liver cirrhosis.

PMID- 25592610
TI  - Mesenchymal stem cells: a friend or foe in immune-mediated diseases.
AB  - Mesenchymal stem cells (MSCs) are adult, self-renewable, multipotent cells that
      can be found in almost all postnatal tissues. Because of their capacity for self
      renewal and differentiation into tissues of mesodermal origin and due to their
      immunomodulatory ability, MSCs are used in many preclinical and clinical studies
      as possible new therapeutic agents for the autoimmune or degenerative diseases
      treatment. In dependence of inflammatory environment to which they are exposed
      to, MSCs adopt immunosuppressive or pro-inflammatory phenotype. In the presence
      of high levels of pro-inflammatory cytokines or through activation of Toll-like
      receptor (TLR)-3, MSCs adopt an immune-suppressive phenotype and suppress the
      proliferation, activation and effector function of professional antigen
      presenting cells (dendritic cells, macrophages, B lymphocytes), T lymphocytes, NK
      cells, NKT cells, and neutrophils. During the early phase of inflammation,
      through TLR4 activation and in the presence of low levels of inflammatory
      cytokines, MSCs adopt a pro-inflammatory phenotype, promote neutrophil and T cell
      activation and enhance immune response. Here we review the current findings on
      the immunoregulatory plasticity of MSCs involved in regulation of immune
      response. 

PMID- 25592613
TI  - Virological and molecular biological evidence supporting herpes simplex virus
      type 1 corneal latency.
AB  - PURPOSE: Trigeminal and other ganglia are known as sites of latent infection by
      herpes simplex virus type 1 (HSV-1). In ophthalmology, HSV-1 remains latent in
      the trigeminal ganglia, and becomes reactivated by several factors, including
      stress, thermal stimulation, or immunosuppression, and may lead to herpetic
      keratitis. The purpose of this study was to demonstrate HSV corneal latent
      infection using molecular biology and virology techniques. METHODS: Six corneas
      obtained at penetrating keratoplasty were snap-frozen; three of them were with
      past history of herpetic keratitis. TaqMan Real-time PCR was used to show
      positive HSV DNA in the corneas. We proved negative homogenate and positive
      explant virologically. Using real-time RT-PCR, we showed that only latency
      associated transcript (LAT) was detected and no transcriptional products of other
      virus genes (alpha, beta, gamma) were detected. RESULTS: All three corneas with
      past history of herpetic keratitis had HSV DNA and showed negative homogenate and
      positive explant. LAT was detected in all three corneas. However, alpha, beta, or
      gamma genes were not expressed. All the results of these corneas were consistent
      with the conditions of corneal latency. The other three corneas without history
      of herpetic keratitis showed negative homogenate and negative explant. None of
      them had LAT. CONCLUSION: We have shown a possibility that HSV can latently
      infect the cornea aside from the ganglion.

PMID- 25592614
TI  - Long-term follow-up of chronic hepatitis C patients treated with interferon
      alpha: risk of cirrhosis and hepatocellular carcinoma in a single center over 10
      years.
AB  - OBJECTIVES: Interferon (IFN)-based therapy for chronic hepatitis C (CHC) is cost
      effective and is associated with reduced risk of disease progression. We aimed to
      assess the incidence of cirrhosis and hepatocellular carcinoma (HCC) and to
      identify risk factors associated with disease progression. METHODS: We
      retrospectively reviewed 280 CHC patients who were registered at our hospital
      between 2001 and 2010. RESULTS: About 80% of patients received antiviral
      treatment. The 10-year cumulative incidence of cirrhosis was significantly lower
      among patients who received antiviral therapy than among those who did not (8.3
      vs. 44.0%; p = 0.001). Among them, patients with sustained virological response
      (SVR) had a significantly lower incidence of cirrhosis than those without SVR
      (0.6 vs. 33.9%; p < 0.001). Cox proportional hazards regression showed that SVR
      was the significant independent factor for reducing the risk of cirrhosis (hazard
      ratio, HR = 0.03; p = 0.034). The 10-year cumulative incidence of HCC was higher
      among patients who did not receive antiviral therapy than among those who did
      (43.9 vs. 6.1%; p < 0.001). Multivariate analysis showed that underlying
      cirrhosis was the only independent risk factor associated with HCC development
      (HR = 7.70; p = 0.010). CONCLUSIONS: SVR secondary to IFN-based therapy could
      reduce cirrhosis development in CHC patients. Underlying cirrhosis was the
      strongest predictor of HCC development.

PMID- 25592615
TI  - Behavioral and psychological symptoms and cognitive decline in patients with
      amnestic MCI and mild AD: a two-year follow-up study.
AB  - BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional
      state between normal aging and dementia. In many cases, MCI represents an early
      stage of developing cognitive impairment. Patients diagnosed with MCI do not meet
      the criteria for dementia as their general intellect and everyday activities are
      preserved, although minor changes in instrumental activities of daily living
      (ADL) may occur. However, they may exhibit significant behavioral and
      psychological signs and symptoms (BPS), also frequently observed in patients with
      Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are
      associated with cognitive decline in participants with MCI or AD. METHODS: Our
      sample consisted of 164 participants, including 46 patients with amnestic (single
      or multi-domain) MCI and 54 patients with AD, as well as 64 control participants
      without cognitive disorders. Global cognitive performance, BPS, and ADL were
      assessed using validated clinical methods at baseline and at two-year follow-up.
      RESULTS: The BPS variability over the follow-up period was more pronounced in the
      MCI group than in patients with AD: some BPS improve, others occur newly or
      worsen, while others still remain unchanged. Moreover, specific changes in BPS
      were associated with a rapid deterioration of the global cognitive level in MCI
      patients. In particular, an increase of euphoria, eating disorders, and aberrant
      motor behavior, as well as worsened sleep quality, predicted a decline in
      cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of
      BPS over time in the MCI group than in AD patients. Moreover, our results provide
      evidence of associations between specific BPS and cognitive decline in the MCI
      group that might suggest a risk of conversion of individuals with amnestic MCI to
      AD.

PMID- 25592616
TI  - Enteric plexuses of two choline-acetyltransferase transgenic mouse lines:
      chemical neuroanatomy of the fluorescent protein-expressing nerve cells.
AB  - We studied cholinergic circuit elements in the enteric nervous system (ENS) of
      two distinct transgenic mouse lines in which fluorescent protein expression was
      driven by the choline-acetyltransferase (ChAT) promoter. In the first mouse line,
      green fluorescent protein was fused to the tau gene. This construct allowed the
      visualization of the fiber tracts and ganglia, however the nerve cells were
      poorly resolved. In the second mouse line (ChATcre-YFP), CRE/loxP recombination
      yielded cytosolic expression of yellow fluorescent protein (YFP). In these
      preparations the morphology of enteric neurons could be well studied. We also
      determined the neurochemical identity of ENS neurons in muscular and submucous
      layers using antibodies against YFP, calretinin (CALR), calbindin (CALB), and
      vasoactive intestinal peptide (VIP). Confocal microscopic imaging was used to
      visualize fluorescently-conjugated secondary antibodies. In ChATcre-YFP
      preparations, YFP was readily apparent in somatodendritic regions of ENS neurons.
      In the myenteric plexus, YFP/CALR/VIP staining revealed that 34% of cholinergic
      cells co-labeled with CALR. Few single-stained CR-positive cells were observed.
      Neither YFP nor CALR co-localized with VIP. In GFP/CALB/CALR staining, all co
      localization combinations were represented. In the submucosal plexus,
      YFP/CALR/VIP staining revealed discrete neuronal populations. However, in
      separate preparations, double labeling was observed for YFP/CALR and CALR/VIP. In
      YFP/CALR/CALB staining, all combinations of double staining and triple labeling
      were verified. In conclusion, the neurochemical coding of ENS neurons in these
      mouse lines is consistent with many observations in non-transgenic animals. Thus,
      they provide useful tools for physiological and pharmacological studies on
      distinct neurochemical subtypes of ENS neurons. 

PMID- 25592618
TI  - The up-regulation of spinal Toll-like receptor 4 in rats with inflammatory pain
      induced by complete Freund's adjuvant.
AB  - Peripheral inflammation induces central sensitization that displays the features
      by the development of pain hypersensitivity to the stimuli. It has been shown
      that activation of glia contributes to the development of behavioral
      hypersensitivity after peripheral inflammation. It has been suggested that Toll
      like receptor 4 (TLR4) primarily expressed on microglia affects central pain
      response. The present study was designed to examine the expressions of TLR4 and
      microglia in the spinal cord in different time points of inflammatory pain
      induced by complete Freund's adjuvant (CFA). The results show that CFA induces
      significant pain hypersensitivity and paw edema as well as spinal dorsal horn
      (SDH) microglia activation with the increased expressions of OX-42 and TLR4
      during the inflammatory pain, respectively. The quantification of TLR4 with
      Western Blot analysis also suggests the same patter with the morphological
      results during the progress of inflammatory pain. In addition, chronic
      minocycline hydrochloride intrathecal injection reverses pain hypersensitivity
      and suppresses activation of microglia and TLR4 induced by CFA, but has hardly
      any effects on paw edema. Taken together, our data demonstrate the importance of
      TLR4 and microglia in rats in CFA inflammatory pain states, and suggest that
      blockade of microglia should likely be considered as a therapeutic opportunity. 

PMID- 25592617
TI  - Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions
      targeting serotonergic synaptic function and cognition.
AB  - Nicotine and chlorpyrifos are developmental neurotoxicants that target serotonin
      systems. We examined whether prenatal nicotine exposure alters the subsequent
      response to chlorpyrifos given postnatally. Pregnant rats received nicotine
      throughout gestation at 3mg/kg/day, a regimen designed to achieve plasma levels
      seen in smokers; chlorpyrifos was given to pups on postnatal days (PN) 1-4 at
      1mg/kg, just above the detection threshold for brain cholinesterase inhibition.
      We assessed long-term effects from adolescence (PN30) through full adulthood
      (PN150), measuring the expression of serotonin receptors and serotonin turnover
      (index of presynaptic impulse activity) in cerebrocortical brain regions
      encompassing the projections that are known targets for nicotine and
      chlorpyrifos. Nicotine or chlorpyrifos individually increased the expression of
      serotonin receptors, with greater effects on males than on females and with
      distinct temporal and regional patterns indicative of adaptive synaptic changes
      rather than simply an extension of initial injury. This interpretation was
      confirmed by our finding an increase in serotonin turnover, connoting presynaptic
      serotonergic hyperactivity. Animals receiving the combined treatment showed a
      reduction in these adaptive effects on receptor binding and turnover relative to
      the individual agents, or even an effect in the opposite direction; further,
      normal sex differences in serotonin receptor concentrations were dissipated or
      reversed, an effect that was confirmed by behavioral evaluations in the Novel
      Objection Recognition Test. In addition to the known liabilities associated with
      maternal smoking during pregnancy, our results point to additional costs in the
      form of heightened vulnerability to neurotoxic chemicals encountered later in
      life. 

PMID- 25592619
TI  - A prospective study of risk for Sturge-Weber syndrome in children with upper
      facial port-wine stain.
AB  - BACKGROUND: Upper facial port-wine stain (PWS) is a feature of Sturge-Weber
      syndrome (SWS). Recent studies suggest that the distribution of the PWS
      corresponds to genetic mosaicism rather than to trigeminal nerve impairment.
      OBJECTIVES: We sought to refine the cutaneous distribution of upper facial PWS at
      risk for SWS. METHODS: This was a prospective multicenter study of consecutive
      cases of upper facial PWS larger than 1 cm2 located in the ophthalmic division of
      trigeminal nerve distribution in infants aged less than 1 year, seen in 8 French
      pediatric dermatology departments between 2006 and 2012. Clinical data, magnetic
      resonance imaging, and photographs were systematically collected and studied. PWS
      were classified into 6 distinct patterns. RESULTS: In all, 66 patients were
      included. Eleven presented with SWS (magnetic resonance imaging signs and
      seizure). Four additional infants had suspected SWS without neurologic
      manifestations. Hemifacial (odds ratio 7.7, P = .003) and median (odds ratio
      17.08, P = .008) PWS patterns were found to be at high risk for SWS. A nonmedian
      linear pattern was not associated with SWS. LIMITATIONS: Small number of patients
      translated to limited power of the study. CONCLUSIONS: Specific PWS distribution
      patterns are associated with an increased risk of SWS. These PWS patterns conform
      to areas of somatic mosaicism. Terminology stipulating ophthalmic division of
      trigeminal nerve territory involvement in SWS should be abandoned.

PMID- 25592621
TI  - Training pattern recognition of skin lesion morphology, configuration, and
      distribution.
AB  - BACKGROUND: The ability to reliably recognize and classify a range of skin signs
      and symptoms remains a necessary skill across most clinical disciplines but one
      that is traditionally mastered via nonsystematic experience over long periods.
      OBJECTIVE: We investigated whether online Perceptual and Adaptive Learning
      Modules (PALMs) could efficiently train preclerkship medical students to identify
      and discriminate primary skin lesion morphologies, configurations, and anatomic
      distributions. METHODS: Medical students completed an online skin lesion
      morphology PALM voluntarily in year 1 and by requirement, along with
      configuration and anatomic distribution PALMs, in year 2. In controlled before
      and-after studies, multiple-choice pretests and posttests using previously unused
      images, assessed PALM-induced learning. In prospective cohort studies,
      differences in year-2 performance between students who had and had not completed
      the morphology PALM in year 1 were also assessed. RESULTS: Multiple-choice tests,
      used to evaluate PALM effectiveness, demonstrated large (effect sizes of 1.1 [+/
      0.1 SE] to 2.2 [+/-0.1 SE]) and statistically significant (P < .0001)
      improvements after PALM training, with learning retention when tested after 1
      year. LIMITATIONS: Results are from self-selected groups and a single class at 1
      institution. CONCLUSION: PALMs are a useful tool for efficient development of the
      core clinical skills of pattern recognition and classification of skin lesion
      characteristics.

PMID- 25592623
TI  - Commentary: mitotic counts in thin melanomas: coming together over division.

PMID- 25592620
TI  - Histologic features of melanoma associated with CDKN2A genotype.
AB  - BACKGROUND: Inherited susceptibility genes have been associated with
      histopathologic characteristics of tumors. OBJECTIVE: We sought to identify
      associations between histology of melanomas and CDKN2A genotype. METHODS: This
      was a case-control study design comparing 28 histopathologic tumor features among
      individuals with sporadic melanomas (N = 81) and cases from melanoma families
      with (N = 123) and without (N = 120) CDKN2A germline mutations. RESULTS: Compared
      with CDKN2A(-) cases, mutation carriers tended to have histologic features of
      superficial spreading melanoma subtype including higher pigmentation (Ptrend =
      .02) and increased pagetoid scatter (Ptrend = .07) after adjusting for age at
      diagnosis, sex, and American Joint Committee on Cancer thickness category.
      Similar associations were observed when comparing mutation carriers with a
      combined group of CDKN2A(-) (wild type) and sporadic melanomas. The presence of
      spindle cell morphology in the vertical growth phase was also an important
      predictor of genotype. Of the 15 cases with this phenotype, none were observed to
      harbor a CDKN2A mutation. LIMITATIONS: Our study examined rare mutations and may
      have been underpowered to detect small, but biologically significant associations
      between histology and genotype. CONCLUSION: Familial melanomas with CDKN2A
      mutations preferentially express a histologic phenotype of dense pigmentation,
      high pagetoid scatter, and a non-spindle cell morphology in the vertical growth
      phase.

PMID- 25592622
TI  - A systematic review of topical corticosteroid withdrawal ("steroid addiction") in
      patients with atopic dermatitis and other dermatoses.
AB  - BACKGROUND: The National Eczema Association has received increasing numbers of
      patient inquiries regarding "steroid addiction syndrome," coinciding with the
      growing presence of social media dedicated to this topic. Although many of the
      side effects of topical corticosteroids (TCS) are addressed in guidelines, TCS
      addiction is not. OBJECTIVE: We sought to assess the current evidence regarding
      addiction/withdrawal. METHODS: We performed a systematic review of the current
      literature. RESULTS: Our initial search yielded 294 results with 34 studies
      meeting inclusion criteria. TCS withdrawal was reported mostly on the face and
      genital area (99.3%) of women (81.0%) primarily in the setting of long-term
      inappropriate use of potent TCS. Burning and stinging were the most frequently
      reported symptoms (65.5%) with erythema being the most common sign (92.3%). TCS
      withdrawal syndrome can be divided into papulopustular and erythematoedematous
      subtypes, with the latter presenting with more burning and edema. LIMITATIONS:
      Low quality of evidence, variability in the extent of data, and the lack of
      studies with rigorous steroid addiction methodology are limitations. CONCLUSIONS:
      TCS withdrawal is likely a distinct clinical adverse effect of TCS misuse.
      Patients and providers should be aware of its clinical presentation and risk
      factors.

PMID- 25592624
TI  - Assessment of tumor mitotic rate in primary cutaneous malignant melanomas 1 mm or
      less in thickness.
AB  - BACKGROUND: Tumor mitotic rate in thin melanomas is recognized as a powerful,
      independent prognostic factor predicting survival. In nonulcerated cases, the
      presence of any dermal mitotic activity upstages the disease to pT1b. The extent
      to which tissue should be histologically examined to assess mitogenicity,
      however, has not been studied. OBJECTIVE: We sought to determine whether in
      staging thin melanomas, there is a significant benefit in examining numerous
      tissue sections containing invasive disease. METHOD: In all, 71 cases of thin
      cutaneous melanomas diagnosed between January 2012 and June 2013 were identified
      after a search performed on the Pathlab database. The slides were retrieved and
      reviewed retrospectively, comparing the identification of the first dermal tumor
      mitotic figure, if present, at 4 check-points: the first, third, fifth, or tenth
      tissue section examined. RESULTS: A statistically significant difference in
      identification of the first dermal mitotic figure was found in examining 1 versus
      3 tissue sections (P = .0411). No significant difference was found in examining
      numerous tissue sections. LIMITATIONS: This was a retrospective study from a
      single institution with a limited number of participants. CONCLUSION: In staging
      thin melanomas without ulceration, the optimal number of sections to assess is 3.
      No additional benefit is gained by examining numerous tissue sections.

PMID- 25592625
TI  - Is cardiovascular evaluation necessary prior to and during beta-blocker therapy
      for infantile hemangiomas?: A cohort study.
AB  - BACKGROUND: Although consensus guidelines for pretreatment evaluation and
      monitoring of propranolol therapy in patients with infantile hemangiomas (IH)
      have been formulated, little is known about the cardiovascular side effects.
      OBJECTIVES: We sought to analyze cardiovascular evaluations in patients with IH
      at baseline and during treatment with an oral beta-blocker. METHODS: Data from
      109 patients with IH were retrospectively analyzed. Patient and family history,
      pretreatment electrocardiogram (ECG), heart rate, and blood pressure were
      evaluated before initiation of beta-blocker therapy. Blood pressure and
      standardized questionnaires addressing side effects were evaluated during
      treatment. RESULTS: Questionnaire analyses (n = 83) identified 3 cases with a
      family history of cardiovascular disease in first-degree relatives. ECG findings
      were normal in each case and no serious complication of therapy occurred. ECG
      abnormalities were found in 6.5% of patients but there were no contraindications
      to beta-blocker therapy and no major complications. Hypotension in 9 patients did
      not require therapy adjustment. In all, 88 parents (81%) reported side effects
      during beta-blocker treatment. LIMITATIONS: The relatively small patient cohort
      is a limitation. CONCLUSION: Pretreatment ECG is of limited value for patients
      with an unremarkable cardiovascular history and a normal heart rate and blood
      pressure. Hypotension may occur during treatment.

PMID- 25592626
TI  - Determinants of length of hospitalization due to acute odontogenic maxillofacial
      infections: a 2009-2013 retrospective analysis.
AB  - OBJECTIVES: To investigate the determinants of the length of hospitalization
      (LOH) due to acute odontogenic maxillofacial infections (AOMIs) from 2009 to
      2013. MATERIALS AND METHODS: Dental records of adult patients with AOMIs and
      related data were retrieved from the Vilnius University's dental hospital. The
      LOH was related to several determinants in each of the following domains:
      outpatient primary care, severity of AOMIs, lifestyle and disease domains.
      Determinants were also associated with the LOH using multivariate analysis.
      RESULTS: A total of 285 patients were hospitalized with AOMIs, of which 166
      (58.2%) were males and 119 (41.8%) were females. The mean LOH was 8.3 +/- 4.9
      days. The bivariate analysis did not reveal any statistically significant
      differences in LOH between patients with AOMIs who received urgent outpatient
      primary care and those who did not receive such care prior to hospitalization.
      All AOMI severity-related determinants were associated with the LOH. The LOH was
      related to coexisting systemic conditions but not to the higher severity of
      dental or periodontal diseases. Both bivariate and multivariate analyses revealed
      similar trends, where the most significant determinants of a longer LOH were
      related to the severity of AOMIs. CONCLUSION: The most important determinants
      regarding longer hospitalization were indicators of infection severity such as an
      extension of the odontogenic infection and the need for an extraoral incision to
      drain the infection.

PMID- 25592627
TI  - How clinical trials of myasthenia gravis can inform pre-clinical drug
      development.
AB  - Pre-clinical evaluations often provide the rationale for therapeutic assessments
      in humans; however, in many diseases an agent found successful in animal models
      does not show efficacy in human subjects. Our contention is that the approach of
      rigorous, clinical trials can be used to inform how preclinical assessments
      should be performed. Clinical trials in humans are carefully designed
      investigations executed with consideration of critical methodological issues,
      such as pre-specified entrance criteria and validated, outcome measures coupled
      with power analysis to identify sample size. Blinding of evaluators of subjective
      measures and randomization of subjects are also critical aspects of trial
      performance. Investigative agents are also tested in subjects with active
      disease, rather than prior to disease induction as in some pre-clinical
      assessments. Application of standard procedures, including uniform reporting
      standards, would likely assist in reproducibility of pre-clinical experiments.
      Adapting methods of clinical trial performance will likely improve the success
      rate of therapeutics to ultimately achieve human use. 

PMID- 25592628
TI  - Solitary lung masses due to occult aspiration.
AB  - BACKGROUND: Aspiration occurs commonly, at times clinically occult, and is
      recognized to cause a widening spectrum of lung disorders. Presentation of
      aspiration as a lung mass has not been described. METHODS: Among cases of
      aspiration-related pulmonary diseases diagnosed at Mayo Clinic (Rochester, Minn)
      from 2007 to 2013, 3 patients were identified to have presented with a solitary
      lung mass lesion. RESULTS: The age of 3 patients, all men with a history of
      gastroesophageal reflux disease, ranged from 53 to 65 years. All patients
      presented with dyspnea, cough, and intermittent fevers. Chest computed tomography
      in each patient demonstrated malignant-appearing solitary lung mass, cavitated in
      2 patients. Two patients underwent positron emission tomography, which showed
      intense fluorodeoxyglucose uptake in the lung mass for both. Surgical lung
      resection revealed acute and organizing pneumonia with giant cell reaction to
      foreign material, consistent with aspiration in all 3 patients. None of these
      lung masses were located in the "dependent" (posterior or basal) lung zones.
      These patients were managed with antireflux medical therapy; 1 patient underwent
      a Nissen fundoplication procedure for recurrent symptoms. No additional
      aspiration-related complications occurred during the follow-up period ranging
      from 24 to 84 months. CONCLUSIONS: Aspiration-related pulmonary complications can
      present as a solitary lung mass that may not be located in dependent lung zones,
      which have traditionally been associated with aspiration-related pulmonary
      diseases.

PMID- 25592629
TI  - Purification and characterisation of a glutamic acid-containing peptide with
      calcium-binding capacity from whey protein hydrolysate.
AB  - The bioavailability of dietary ionised calcium is affected by intestinal basic
      environment. Calcium-binding peptides can form complexes with calcium to improve
      its absorption and bioavailability. The aim of this study was focused on
      isolation and characterisation of a calcium-binding peptide from whey protein
      hydrolysates. Whey protein was hydrolysed using Flavourzyme and Protamex with
      substrate to enzyme ratio of 25:1 (w/w) at 49  degrees C for 7 h. The calcium
      binding peptide was isolated by DEAE anion-exchange chromatography, Sephadex G-25
      gel filtration and reversed phase high-performance liquid chromatography (RP
      HPLC). A purified peptide of molecular mass 204 Da with strong calcium binding
      ability was identified on chromatography/electrospray ionisation (LC/ESI) tandem
      mass spectrum to be Glu-Gly (EG) after analysis and alignment in database. The
      calcium binding capacity of EG reached 67.81 MUg/mg, and the amount increased by
      95% compared with whey protein hydrolysate complex. The UV and infrared
      spectrometer analysis demonstrated that the principal sites of calcium-binding
      corresponded to the carboxyl groups and carbonyl groups of glutamic acid. In
      addition, the amino group and peptide amino are also the related groups in the
      interaction between EG and calcium ion. Meanwhile, the sequestered calcium
      percentage experiment has proved that EG-Ca is significantly more stable than
      CaCl2 in human gastrointestinal tract in vitro. The findings suggest that the
      purified dipeptide has the potential to be used as ion-binding ingredient in
      dietary supplements.

PMID- 25592630
TI  - Bioactivity of water soluble extracts and some characteristics of white cheese
      during the ripening period as effected by packaging type and probiotic adjunct
      cultures.
AB  - In this study, the chemical composition, proteolysis and in vitro angiotensin
      converting enzyme-(ACE)-inhibitory and antioxidant activities of white cheeses
      made using probiotic adjunct cultures (Bifidobacterium bifidum DSMZ 20456 and
      Lactobacillus acidophilus DSMZ 20079) were investigated. The cheeses were ripened
      in a vacuum package or brine for 120 d at 4  degrees C. The cheese samples
      maintained the probiotic characteristics of the viable cells as >106 cfu/g even
      after ripening for 120 d. The proteolysis degrees in terms of water-soluble
      nitrogen/total nitrogen (WSN/TN), trichloroacetic acid-soluble nitrogen/total
      nitrogen (TCA-SN/TN) and phosphotungstic acid-soluble nitrogen/total nitrogen
      (PTA-SN/TN) values in the cheeses increased throughout the ripening. The highest
      levels of proteolysis were found in cheese made using Lb. acidophilus DSMZ 20079
      and ripened in a vacuum package. ACE-inhibitory activity of the water soluble
      extracts (WSEs) of the cheeses increased significantly (P < 0.05) throughout the
      ripening (IC50 values 82.78-140.99 MUg/ml). Use of Lb. acidophilus DSMZ 20079 and
      packaging under vacuum significantly increased the percentage of ACE inhibiting
      activity. WSEs had DPPH scavenging activity (the IC50 values were 2.41-5.39 mg/ml
      and the inhibition values were 5.10-10.38%), increasing up to 60 d ripening. In
      the present study, it was observed that Lb. acidophilus DSMZ 20079 was more
      effective than Bifido. bifidum DSMZ 20456 in terms of the cheese characteristics
      investigated. 

PMID- 25592631
TI  - Mammary gland development of dairy heifers fed diets containing increasing levels
      of metabolisable protein: metabolisable energy.
AB  - This study was conducted to evaluate the development of the mammary gland in
      Holstein heifers subjected to different dietary metabolisable protein (MP):
      metabolisable energy (ME) ratios. Twenty-five Holstein heifers (initial body
      weight (BW) 213+/-13.5 kg and initial average age 7.8+/-0.5 months) were divided
      into five treatments. The treatments were designed to provide MP:ME ratios equal
      to 33, 38, 43, 48, and 53 g of MP per Mcal of ME. All diets were formulated to
      have the same energy content (2.6 Mcal ME/kg dry matter). Actual MP:ME ratios
      were 36.2, 40.2, 46.2, 47.1, and 50.8 g MP/Mcal ME. The experiment was conducted
      in a randomised block design, while considering initial BW as a blocking factor
      to evaluate pre- and post-pubertal periods. Block effect was not observed for all
      variables evaluated; hence it was considered that the diets had the same
      influence both on pre- and post-pubertal phases. Dry matter and nutrient intake
      did not change between treatments, excepting protein intake and digestibility.
      Serum concentrations of insulin-like growth factor 1 increased linearly across
      treatments. Changes in the pixel brightness of mammary gland ultrasound images,
      which are associated with lipid content, were significantly influenced by MP:ME
      ratios in the diet of heifers that were subjected to accelerated growth rates. It
      is not recommended to use diets of less than 38 g MP/Mcal ME in diets to heifers
      allowed to gain more than 1 kg/d. 

PMID- 25592633
TI  - Sunitinib in thymic carcinoma: enigmas still unresolved.

PMID- 25592632
TI  - Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma:
      an open-label phase 2 trial.
AB  - BACKGROUND: No standard treatments are available for advanced thymic epithelial
      tumours after failure of platinum-based chemotherapy. We investigated the
      activity of sunitinib, an orally administered tyrosine kinase inhibitor. METHODS:
      Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in
      patients with histologically confirmed chemotherapy-refractory thymic epithelial
      tumours. Patients were eligible if they had disease progression after at least
      one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative
      Oncology Group performance status of two or lower, measurable disease, and
      adequate organ function. Patients received 50 mg of sunitinib orally once a day,
      in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without
      treatment), until tumour progression or unacceptable toxic effects arose. The
      primary endpoint was investigator-assessed best tumour response at any point,
      which we analysed separately in thymoma and thymic carcinoma cohorts. Patients
      who had received at least one cycle of treatment and had their disease reassessed
      were included in the analyses of response. The trial was registered with
      ClinicalTrials.gov, number NCT01621568. FINDINGS: 41 patients were enrolled, 25
      with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was
      deemed ineligible after enrolment and did not receive protocol treatment. Of
      patients who received treatment, one individual with thymic carcinoma was not
      assessable because she died. Median follow-up on trial was 17 months (IQR 14.0
      18.4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12.1
      45.3, 95% CI 10.2-48.4) had partial responses, 15 (65%, 95% CI 42.7-83.6)
      achieved stable disease, and two (9%, 1.1-28.0) had progressive disease. Of 16
      patients with thymoma, one (6%, 95% CI 0.2-30.2) had a partial response, 12 (75%,
      47.6-92.7) had stable disease, and three (19%, 4.1-45.7) had progressive disease.
      The most common grade 3 and 4 treatment-related adverse events were
      lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral
      mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular
      ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients
      died during treatment, including one individual who died of cardiac arrest that
      was possibly treatment-related. INTERPRETATION: Sunitinib is active in previously
      treated patients with thymic carcinoma. Further studies are needed to identify
      potential biomarkers of activity. FUNDING: National Cancer Institute (Cancer
      Therapy Evaluation Program).

PMID- 25592634
TI  - Time-dependent changes of plasma inflammatory biomarkers in type A aortic
      dissection patients without optimal medical management.
AB  - OBJECTIVES: To investigate the time-dependent changes in plasma levels of
      interleukin-6, C-reactive protein, and tumor necrosis factor-alpha in patients
      with type A aortic dissection (TAAD) who received unoptimal medical management
      since the onset of dissections. DESIGN AND METHODS: Plasma levels of interleukin
      6, C-reactive protein, and tumor necrosis factor-alpha were detected by ELISA and
      immuno-turbidimetric assay in 92 TAAD patients at hospital admission. Blood
      samples from 78 patients with uncontrolled hypertension and 82 healthy volunteers
      were also analyzed as controls. The occurrence of TAAD-related complication and
      its relationship with the plasma levels of these inflammatory biomarkers was also
      investigated. RESULTS: The concentrations of inflammatory mediators were
      significant higher in TAAD than those in the uncontrolled hypertension and the
      healthy group. The time to peak plasma level of IL-6.and TNF-alpha was shorter
      than that of CRP in TAAD group. In the TAAD group, 51 patients suffered TAAD
      related complications, and their plasma level of CRP was significantly higher
      than that in patients without TAAD-related complications (94.5 +/- 58.8 mg/L
      versus 47.4 +/- 47.8 mg/L, p < 0.001). Also, CRP levels strongly correlated with
      the value of PaO2/FiO2 ratio (r = -0.69, p < 0.001) and creatinine (r = 0.60, p <
      0.001). The time to the peak level of CRP was shorter and the duration of
      persistently high CRP level was longer in the complication group than those in
      the complication-free group. CONCLUSIONS: Elevated and persistently high levels
      of plasma CRP, IL-6 and TNF-alpha were associated with progressively development
      of the TAAD. The changing pattern of CRP might be a marker for diagnosis and
      prophylactic treatment of complications. Our findings suggested a critical role
      of the inflammation in the progression of dissection and TAAD-related
      complications.

PMID- 25592635
TI  - 16S rRNA and As-Related Functional Diversity: Contrasting Fingerprints in Arsenic
      Rich Sediments from an Acid Mine Drainage.
AB  - To gain an in-depth insight into the diversity and the distribution of genes
      under the particular evolutionary pressure of an arsenic-rich acid mine drainage
      (AMD), the genes involved in bacterial arsenic detoxification (arsB, ACR3) and
      arsenite oxidation (aioA) were investigated in sediment from Carnoules (France),
      in parallel to the diversity and global distribution of the metabolically active
      bacteria. The metabolically active bacteria were affiliated mainly to AMD
      specialists, i.e., organisms detected in or isolated from AMDs throughout the
      world. They included mainly Acidobacteria and the non-affiliated "Candidatus
      Fodinabacter communificans," as well as Thiomonas and Acidithiobacillus spp.,
      Actinobacteria, and unclassified Gammaproteobacteria. The distribution range of
      these organisms suggested that they show niche conservatism. Sixteen types of
      deduced protein sequences of arsenite transporters (5 ArsB and 11 Acr3p) were
      detected, whereas a single type of arsenite oxidase (AioA) was found. Our data
      suggested that at Carnoules, the aioA gene was more recent than those encoding
      arsenite transporters and subjected to a different molecular evolution. In
      contrast to the 16S ribosomal RNA (16S rRNA) genes associated with AMD
      environments worldwide, the functional genes aioA, ACR3, and to a lesser extent
      arsB, were either novel or specific to Carnoules, raising the question as to
      whether these functional genes are specific to high concentrations of arsenic,
      AMD-specific, or site-specific. 

PMID- 25592636
TI  - Pond sediment magnetite grains show a distinctive microbial community.
AB  - Formation of magnetite in anaerobic sediments is thought to be enhanced by the
      activities of iron-reducing bacteria. Geobacter has been implicated as playing a
      major role, as in culture its cells are often associated with extracellular
      magnetite grains. We studied the bacterial community associated with magnetite
      grains in sediment of a freshwater pond in South Korea. Magnetite was isolated
      from the sediment using a magnet. The magnetite-depleted fraction of sediment was
      also taken for comparison. DNA was extracted from each set of samples, followed
      by PCR for 16S bacterial ribosomal RNA (rRNA) gene and HiSeq sequencing. The
      bacterial communities of the magnetite-enriched and magnetite-depleted fractions
      were significantly different. The enrichment of three abundant operational
      taxonomic units (OTUs) suggests that they may either be dependent upon the
      magnetite grain environment or may be playing a role in magnetite formation. The
      most abundant OTU in magnetite-enriched fractions was Geobacter, bolstering the
      case that this genus is important in magnetite formation in natural systems.
      Other major OTUs strongly associated with the magnetite-enriched fraction, rather
      than the magnetite-depleted fraction, include a Sulfuricella and a novel member
      of the Betaproteobacteria. The existence of distinct bacterial communities
      associated with particular mineral grain types may also be an example of niche
      separation and coexistence in sediments and soils, which cannot usually be
      detected due to difficulties in separating and concentrating minerals. 

PMID- 25592637
TI  - Diversity, Abundance, and Distribution of nirS-Harboring Denitrifiers in
      Intertidal Sediments of the Yangtze Estuary.
AB  - Denitrification plays a critical role in nitrogen removal in estuarine and
      coastal ecosystems. In this study, the community composition, diversity,
      abundance, and distribution of cytochrome cd1-type nitrite reductase gene (nirS)
      harboring denitrifiers in intertidal sediments of the Yangtze Estuary were
      analyzed using polymerase chain reaction (PCR)-based clone libraries and
      quantitative PCR techniques. Clone library analysis showed that the nirS-encoding
      bacterial biodiversity was significantly higher at the lower salinity sites than
      at the higher salinity sites. However, there was no significant seasonal
      difference in the nirS gene diversity between summer and winter. Phylogenetic
      analysis revealed that the nirS-harboring denitrifier communities at the study
      area had distinctive spatial heterogeneity along the estuary. At the lower
      salinity sites, the nirS-harboring bacterial community was co-dominated by
      clusters III and VII; while at the higher salinity sites, it was dominated by
      cluster I. Canonical correspondence analysis indicated that the community
      compositions of nirS-type denitrifiers were significantly correlated with
      salinity, ammonium, and nitrate. Quantitative PCR results showed that the nirS
      gene abundance was in the range of 1.01 * 10(6) to 9.00 * 10(7) copies per gram
      dry sediment, without significant seasonal variation. Among all the environmental
      factors, the nirS gene abundance was only significantly related to the change of
      salinity. These results can extend our current knowledge about the composition
      and dynamics of denitrification microbial community in the estuarine ecosystem.

PMID- 25592639
TI  - DNA nanotechnology for nanophotonic applications.
AB  - DNA nanotechnology has touched the epitome of miniaturization by integrating
      various nanometer size particles with nanometer precision. This enticing bottom
      up approach has employed small DNA tiles, large multi-dimensional polymeric
      structures or more recently DNA origami to organize nanoparticles of different
      inorganic materials, small organic molecules or macro-biomolecules like proteins,
      and RNAs into fascinating patterns that are difficult to achieve by other
      conventional methods. Here, we are especially interested in the self-assembly of
      nanomaterials that are potentially attractive elements in the burgeoning field of
      nanophotonics. These materials include plasmonic nanoparticles, quantum dots,
      fluorescent organic dyes, etc. DNA based self-assembly allows excellent control
      over distance, orientation and stoichiometry of these nano-elements that helps to
      engineer intelligent systems that can potentially pave the path for future
      technology. Many outstanding structures have been fabricated that are capable of
      fine tuning optical properties, such as fluorescence intensity and lifetime
      modulation, enhancement of Raman scattering and emergence of circular dichroism
      responses. Within the limited scope of this review we have tried to give a
      glimpse of the development of this still nascent but highly promising field to
      its current status as well as the existing challenges before us. 

PMID- 25592638
TI  - Antinociceptive synergism of gabapentin and nortriptyline in mice with partial
      sciatic nerve ligation.
AB  - BACKGROUND AND METHODS: Neuropathic pain results from nerve injury, and
      gabapentin, an antiepileptic drug, has been approved for the treatment of several
      types of neuropathic pain. On the other hand, nortriptyline, an antidepressant
      drug, has been suggested as an alternative treatment. In partial sciatic nerve
      ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was
      evaluated by the hot plate assay using isobolographic analysis. RESULTS:
      Gabapentin (3-100 mg/kg, i.p.) or nortriptyline (1-30 mg/kg, i.p.) induced dose
      dependent antinociception, with an ED50 of 11.60 +/- 0.54 mg/kg for gabapentin
      and of 5.16 +/- 0.21 mg/kg for nortriptyline. The potency of gabapentin and
      nortriptyline in PSNL mice at 7 and 14 days after ligation was significantly
      increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1:1
      ratio of their ED50, had a synergistic effect, with an interaction index of 0.311
      and 0.348 for these mice at 7 and 14 days, respectively. CONCLUSION: The data
      showed a synergy in antinociception at a gabapentin-to-nortriptyline ratio of 1:1
      in PSNL mice. This finding suggests that this combination could provide a
      therapeutic alternative that can be used for neuropathic pain management.

PMID- 25592640
TI  - Developmental variations in environmental influences including endocrine
      disruptors on pubertal timing and neuroendocrine control: Revision of human
      observations and mechanistic insight from rodents.
AB  - Puberty presents remarkable individual differences in timing reaching over 5
      years in humans. We put emphasis on the two edges of the age distribution of
      pubertal signs in humans and point to an extended distribution towards earliness
      for initial pubertal stages and towards lateness for final pubertal stages. Such
      distortion of distribution is a recent phenomenon. This suggests changing
      environmental influences including the possible role of nutrition, stress and
      endocrine disruptors. Our ability to assess neuroendocrine effects and mechanisms
      is very limited in humans. Using the rodent as a model, we examine the impact of
      environmental factors on the individual variations in pubertal timing and the
      possible underlying mechanisms. The capacity of environmental factors to shape
      functioning of the neuroendocrine system is thought to be maximal during fetal
      and early postnatal life and possibly less important when approaching the time of
      onset of puberty.

PMID- 25592641
TI  - Orofacial granulomatosis: clinical signs of different pathologies.
AB  - Orofacial granulomatosis (OFG) is an uncommon disease characterized by persistent
      or recurrent soft tissue enlargement, oral ulceration and a variety of other
      orofacial features. It could be an oral manifestation of a systemic disease. For
      a correct differential diagnosis, local and systemic conditions characterized by
      granulomatous inflammation should be excluded using appropriate clinical and
      laboratory investigations. In fact, the diagnosis of OFG may be confirmed only by
      histopathological identification of noncaseating granulomas. The literature from
      1943 to 2014 was reviewed with emphasis on the etiology of OFG and on clinical
      manifestations of systemic pathologies associated with OFG. The precise cause of
      OFG is still unknown, although several theories have been suggested, such as
      infection, hereditary factors and allergy. OFG is a disease that has a wide
      spectrum of presentation, which may include the oral manifestation of a systemic
      condition such as Crohn's disease, sarcoidosis, granulomatosis with polyangiitis
      and Melkersson-Rosenthal syndrome.

PMID- 25592642
TI  - Improving the pre-screening of eligible patients in order to increase enrollment
      in cancer clinical trials.
AB  - BACKGROUND: The performance of randomized controlled trials (RCTs) is often
      hindered by recruitment difficulties. This study aims to explore the pre
      screening phase of four prostate cancer RCTs to identify the impact of a
      systematic pre-selection of eligible patients for RCT recruitment. METHODS: The
      pre-screening of four RCTs opened at the Comprehensive Cancer Center in Rennes
      was analyzed retrospectively (French Genitourinary Tumor Group (GETUG) 14, 15,
      16, and 17). Data were extracted from electronic multidisciplinary cancer (MDC)
      reports and manually completed by physicians and medical secretaries. These data
      were the main source of information for clinicians to discuss treatment
      alternatives during MDC sessions. The pre-screening decisions made by the
      clinicians during these MDC meetings were compared with those made after a
      systematic review of the MDC reports by a clinical research assistant (CRA). Any
      inconsistencies in decisions between the CRA and the MDC physicians were
      corrected by the principal investigator (PI). RESULTS: The pre-screening rate was
      9.1% during the MDC meetings, while it was estimated to be 12.9% after the final
      review by the PI, and 29% after the systematic review by the CRA. The study
      showed that 77% and 67% of the MDC reports did not mention clinical and
      pathological Tumor, lymph node and metastasis classification of malignant tumors
      (TNM) staging, respectively, and that 35 of the CRA's 47 proposals rejected by
      the PI concerned implicit information (not specified in the MDC reports). Only
      one patient was proposed by the PI, and none by the CRA. CONCLUSIONS: These
      results confirm that pre-screening could be improved by a systematic review of
      the medical reports. They also highlight the fact that missing data in electronic
      MDC reports leads to over-enrollment of non-eligible patients, but not to over
      exclusion of eligible patients. Thus, our study confirms the potential gain in
      using semi-automated pre-selection of MDC reports, in order to avoid missing out
      on patients eligible for RCTs. TRIAL REGISTRATION: The trials evaluated in this
      study were previously registered with clinicaltrials.gov (registration number:
      NCT00104741 on 3 March 2005; NCT00104715 on 3 March 2005; NCT00423475 on 16
      January 2007; and NCT00667069 on 24 April 2008).

PMID- 25592644
TI  - [Sclerosing lymphangitis of the penis].

PMID- 25592643
TI  - Implication of high risk human papillomavirus HR-HPV infection in prostate cancer
      in Indian population--a pioneering case-control analysis.
AB  - Prostate cancer is the second most common cancer with sexual history as a
      consistent risk factor. This is the pioneering study that evaluates the frequency
      of HPV infection in prostate cancer in India. Ninety five (95)
      histopathologically confirmed cancer and fifty five (55) BPH from Indian
      population were analyzed for HPV infection using a pair of consensus sequence
      primer followed by type specific PCRs for both high-risk and low-risk HPV types.
      The data demonstrate HPV infection in 41% of prostate tumor biopsies and 20% in
      BPH. Subsequent PCR- based HPV typing using type - specific primers revealed 32%
      were infected with HPV type 16 whereas 6% were found to be positive for HPV type
      18, while in BPH controls only 5% of the BPH controls were infected with HPV 16
      and this difference was highly significant (p = 0.0004). Significant proportion
      of HPV infected (74%) cases belonged to stage III and IV (p < 0.001) with a high
      Gleason score >= 8 (p = 0.003). The study represents for the first time the
      incidence of HPV infection in prostate cancer in Indian population and
      strengthens the hypothesis that HPV infection could be one of the co factor
      associated with progression of prostate cancer.

PMID- 25592645
TI  - Major declines in epoetin dosing after prospective payment system based on
      dialysis facility organizational status.
AB  - BACKGROUND: Epoetin therapy used to treat anemia among ESRD patients has cost
      Medicare ~$40 billion. Since January 2011, epoetin has been reimbursed via a new
      bundled prospective payment system (PPS). Our aim was to determine changes in
      epoetin dosing and hematocrit levels in response to PPS by different types of
      dialysis providers. METHODS: Data from the USRDS were used to identify 187,591
      and 206,163 Medicare-eligible ESRD patients receiving hemodialysis during January
      2010 (pre-PPS) and December 2011 (post-PPS). Standardized weekly mean epoetin
      dose administered pre- and post-PPS and adjustment in dose (titration) based on
      previous hematocrit level in each facility was disaggregated by profit status,
      chain membership and size. RESULTS: Major declines in epoetin use, dosing and
      achieved hematocrit levels were observed after PPS. Among the three largest
      dialysis chains, the decline in standardized epoetin dose was 29% at Fresenius,
      47% at DaVita, and 52% at DCI. The standardized weekly epoetin dose among profit
      and nonprofit facilities declined by 38 and 42%, respectively. Changes in
      titration patterns suggest that a new hematocrit target of 30-33% was in place
      after PPS, replacing the erstwhile 33-36% hematocrit target used before PPS.
      CONCLUSION: Historically, important differences in anemia management were evident
      by dialysis organizational status. However, the confluence of financial
      incentives bundling epoetin payments and mounting scientific evidence linking
      higher hematocrit targets and higher epoetin doses to adverse outcomes have
      culminated in lower access to epoetin and lower doses across all dialysis
      providers in the first year after PPS.

PMID- 25592646
TI  - Intra-tumoural vessel area estimated by expression of epidermal growth factor
      like domain 7 and microRNA-126 in primary tumours and metastases of patients with
      colorectal cancer: a descriptive study.
AB  - BACKGROUND: Understanding the biological properties of potential drug targets are
      important. This is especially true for anti-angiogenic therapies in the search
      for potential biomarkers. The aim of the present descriptive study was to analyse
      the intra-tumoural expressions of epidermal growth factor-like domain 7 (EGFL7)
      and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV
      colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph
      node metastases and distant metastases. METHODS: A total of 126 patients were
      included. Analyses were performed on resections of primary tumours, regional
      lymph node metastases, and large needle biopsies from distant metastases. EGFL7
      was analysed by immunohistochemistry (IHC) and miRNA-126 by in situ hybridization
      (ISH). Both biomarkers were quantified by image guided analyses to determine the
      relative fraction estimates of vessel areas (VA). RESULTS: The intra-tumoural
      EGFL7 VA was significantly higher in primary tumours from patients with recurrent
      disease than in patients without relapse in both stage II and III, p = 0.019 and
      p = 0.001, respectively. The EGFL7 VA was significantly higher and the miRNA-126
      VA significantly lower in regional lymph node metastases compared to primary
      tumours, p = 0.01 and p < 10(-6), respectively. Furthermore, the miRNA-126 VA in
      liver metastases was significantly lower than in the primary tumours, p = 0.02.
      CONCLUSION: The intra-tumoural expression of EGFL7 in early stages of CRC may
      influence the risk of post-surgical recurrence. Differential expression of miRNA
      126 seems more pronounced in disseminated disease, which supports its role as a
      regulator in the metastatic process.

PMID- 25592649
TI  - Decomposing the space of protein quaternary structures with the interface
      fragment pair library.
AB  - BACKGROUND: The physical interactions between proteins constitute the basis of
      protein quaternary structures. They dominate many biological processes in living
      cells. Deciphering the structural features of interacting proteins is essential
      to understand their cellular functions. Similar to the space of protein tertiary
      structures in which discrete patterns are clearly observed on fold or sub-fold
      motif levels, it has been found that the space of protein quaternary structures
      is highly degenerate due to the packing of compact secondary structure elements
      at interfaces. Therefore, it is necessary to further decompose the protein
      quaternary structural space into a more local representation. RESULTS: Here we
      constructed an interface fragment pair library from the current structure
      database of protein complexes. After structural-based clustering, we found that
      more than 90% of these interface fragment pairs can be represented by a limited
      number of highly abundant motifs. These motifs were further used to guide complex
      assembly. A large-scale benchmark test shows that the native-like binding is
      highly likely in the structural ensemble of modeled protein complexes that were
      built through the library. CONCLUSIONS: Our study therefore presents supportive
      evidences that the space of protein quaternary structures can be represented by
      the combination of a small set of secondary-structure-based packing at binding
      interfaces. Finally, after future improvements such as adding sequence profiles,
      we expect this new library will be useful to predict structures of unknown
      protein-protein interactions.

PMID- 25592650
TI  - Rivaroxaban as anticoagulant therapy in short bowel syndrome. Report of three
      cases.

PMID- 25592651
TI  - Hypercoagulability detected by whole blood thromboelastometry (ROTEM(r)) and
      impedance aggregometry (MULTIPLATE(r)) in obese patients.
AB  - INTRODUCTION: Obesity has been associated with hypercoagulability and to
      increased risk of both arterial and venous thromboembolic events. Many different
      and complex changes in plasma coagulation factors have been described in patients
      with obesity. The aim of this case-control study is to evaluate
      hypercoagulability in a group of overweight and obese subjects by whole blood
      rotation thromboelastometry (ROTEM(r)) and impedance aggregometry
      (Multiplate(r)). METHODS: ROTEM(r) and Multiplate(r) analyses were performed in
      80 subjects with a BMI >= 25 Kg/m(2), of whom 20 overweight [BMI = 25-29.9
      Kg/m(2)], 20 with I degree obesity [BMI = 30-34.9 Kg/m(2)], 20 with II degree
      obesity [BMI = 35-39.9 Kg/m(2)] and 20 with III degree [BMI > 40 Kg/m(2)] and
      compared with 80 age and gender-matched normal weight healthy individuals.
      RESULTS: Thromboelastometry. In INTEM and EXTEM tests MCF and AUC were
      significantly increased in III degree obese compared with controls. MCF in FIBTEM
      was significantly higher in I, II and III degree obesity than controls (p =
      0.027, 0.002 and < 0.001, respectively). Impedance aggregometry. A significant
      difference in platelet aggregation was found between III degree obese subjects
      and healthy controls in each of the tests considered. A significant correlation
      between FIBTEM-MCF and aggregometry parameters with BMI, waist circumference,
      leptin levels and high sensitive-C reactive proteins was also found. CONCLUSIONS:
      A relationship between hypercoagulability detected by whole blood
      thromboelastometry and aggregometry and increased fat mass is shown.
      Hypercoagulability also correlated with inflammatory markers. Point-of-care tests
      can be used to assess the degree of hypercoagulability and hyperaggregability in
      obese patients. Wider studies are needed to confirm our observations.

PMID- 25592648
TI  - The emerging roles of YAP and TAZ in cancer.
AB  - Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding
      motif (TAZ) are the major downstream effectors of the Hippo pathway, which
      regulates tissue homeostasis, organ size, regeneration and tumorigenesis. In this
      Progress article, we summarize the current understanding of the biological
      functions of YAP and TAZ, and how the regulation of these two proteins can be
      disrupted in cancer. We also highlight recent findings on their expanding role in
      cancer progression and describe the potential of these targets for therapeutic
      intervention.

PMID- 25592652
TI  - Correction of hyper- and hyponatraemia during continuous renal replacement
      therapy.
AB  - BACKGROUND: Severe hyper- and hyponatraemia is associated with significant risks,
      yet its correction can also have serious consequences when implemented too fast
      or inadequately. The safe correction of serum sodium levels is particularly
      challenging when renal replacement therapy (RRT) is required. METHODS: Using 2
      case scenarios, we aim to illustrate a simple method of correcting hyper- and
      hyponatraemia safely by step-wise manipulation of the dialysate/replacement
      fluid. RESULTS: During continuous RRT, hypernatraemia can be corrected
      effectively and safely by adding small pre-calculated amounts of 30% NaCl to the
      dialysate/replacement fluid bags aiming for a [Na(+)] in the fluid that allows
      safe equilibration and correction of the serum [Na(+)]. To correct hyponatraemia
      safely, pre-calculated amounts of sterile water can be added in a step-wise
      manner to achieve a fluid [Na(+)] that equals the desired target serum [Na(+)].
      CONCLUSION: During continuous RRT, the step-wise adjustment of [Na(+)] of
      dialysate/replacement fluids offers a safe and reliable method to correct sodium
      disorders.

PMID- 25592653
TI  - [The VR, the Russian version of the nerve agent VX].
AB  - A product of the arms race during the Cold War, the Russian VX, or VR, is an
      organophosphorus compound that is a structural isomer of the western VX compound
      (or A4), with which it shares a very high toxicity. It is much less studied and
      known than VX because the knowledge of its existence is relatively recent. A very
      low volatility and high resistance in the environment make it a persistent agent.
      Poisoning occurs mainly following penetration through skin and mucosa but vapour
      inhalation is a credible risk in some circumstances. The clinical presentation
      may be differed by several hours and despite the absence of signs and symptoms,
      the casualty should not be considered as contamination or intoxication-free. This
      agent has a long residence time in blood, a characteristics that clearly
      differentiates it from other compounds such as sarin. The protocols for antidote
      administration may thus have to be changed accordingly. The fact that VR poisoned
      individuals will less respond to the current oxime therapy used in France, the 2
      PAM and that VR represents a higher threat than VX, being probably possessed by
      some proliferating states, justify the interest for this toxic product. 

PMID- 25592647
TI  - The RUNX family: developmental regulators in cancer.
AB  - RUNX proteins belong to a family of metazoan transcription factors that serve as
      master regulators of development. They are frequently deregulated in human
      cancers, indicating a prominent and, at times, paradoxical role in cancer
      pathogenesis. The contextual cues that direct RUNX function represent a fast
      growing field in cancer research and could provide insights that are applicable
      to early cancer detection and treatment. This Review describes how RUNX proteins
      communicate with key signalling pathways during the multistep progression to
      malignancy; in particular, we highlight the emerging partnership of RUNX with p53
      in cancer suppression. 

PMID- 25592654
TI  - Fully covered self-expandable metal stent in tracheobronchial disorders: clinical
      experience.
AB  - BACKGROUND: The third-generation fully covered self-expandable metallic stent
      (SEMS) has been developed to solve the problems of difficult removal and in-stent
      granuloma formation related to the uncovered or partially covered type. There are
      few written reports about the performance of this type of stents with early
      encouraging results. OBJECTIVES: To report and analyse our experience with the
      Silmet(r) stent in the management of malignant and benign tracheobronchial
      disorders. METHODS: We retrospectively reviewed medical records of patients who
      underwent fully covered SEMS Silmet placement at the Interventional Pulmonology
      Unit, La Maddalena Cancer Center, Palermo, Italy, between May 2010 and August
      2013. RESULTS: Stents were placed in 52 patients with malignant (n = 49) and
      benign airway obstruction (n = 2) and broncho-oesophageal fistula (n = 1). SEMSs
      were inserted into the trachea (n = 19), the main bronchi (n = 21) and the
      peripheral bronchi (n = 31). Besides 1 procedural dislocation, the deployment was
      successful in all patients with an immediate significant improvement of symptoms
      (Barthel Index p < 0.001; Medical Research Council score p < 0.001). A
      radiographic improvement was detected in 48% of patients. The mean follow-up
      duration was 119 +/- 120 days (range 22-549 days). Complications observed were:
      migration (7.6%), tumour overgrowth (15%), infections (5.7%), granulation tissue
      formation (3.8%) and mucus plug (3.8%). CONCLUSIONS: The Silmet stent is
      effective, safe and simple to implant and remove. We suggest its use in cases of
      tight stenoses, in the treatment of small- to medium-caliber airways or in cases
      of tortuous airways.

PMID- 25592655
TI  - Clinical relevance of Pseudomonas aeruginosa hypermutation in cystic fibrosis
      chronic respiratory infection: Response to Dr. Oliver.

PMID- 25592656
TI  - A phase 3, open-label, randomized trial to evaluate the safety and efficacy of
      levofloxacin inhalation solution (APT-1026) versus tobramycin inhalation solution
      in stable cystic fibrosis patients.
AB  - BACKGROUND: Inhaled antibiotics are standard of care for persons with cystic
      fibrosis (CF) and chronic Pseudomonas aeruginosa airway infection. APT-1026
      (levofloxacin inhalation solution, LIS) is fluoroquinolone in development. We
      compared the safety and efficacy of LIS to tobramycin inhalation solution (TIS)
      in persons >=12 years old with CF and chronic P. aeruginosa infection. METHODS:
      This multinational, randomized (2:1), non-inferiority study compared LIS and TIS
      over three 28-day on/off cycles. Day 28 FEV(1) % predicted relative change was
      the primary endpoint. Time to exacerbation and patient-reported quality of life
      were among secondary endpoints. RESULTS: Baseline demographics for 282 subjects
      were comparable. Non-inferiority was demonstrated (1.86% predicted mean FEV(1)
      difference [95% CI -0.66 to 4.39%]). LIS was well-tolerated, with dysgeusia
      (taste distortion) as the most frequent adverse event. CONCLUSIONS: LIS is a safe
      and effective therapy for the management of CF patients with chronic P.
      aeruginosa infection.

PMID- 25592657
TI  - Cystic Fibrosis Foundation and European Cystic Fibrosis Society Survey of cystic
      fibrosis mental health care delivery.
AB  - BACKGROUND: Psychological morbidity in individuals with cystic fibrosis (CF) and
      their caregivers is common. The Cystic Fibrosis Foundation (CFF) and European
      Cystic Fibrosis Society (ECFS) Guidelines Committee on Mental Health sought the
      views of CF health care professionals concerning mental health care delivery.
      METHODS: An online survey which focused on the current provision and barriers to
      mental health care was distributed to CF health care professionals. RESULTS: Of
      the 1454 respondents, many did not have a colleague trained in mental health
      issues and 20% had no one on their team whose primary role was focused on
      assessing or treating these issues. Insufficient resources and a lack of
      competency were reported in relation to mental health referrals. Seventy-three
      percent of respondents had no experience with mental health screening. Of those
      who did, they utilized 48 different, validated scales. CONCLUSIONS: These data
      have informed the decision-making, dissemination and implementation strategies of
      the Mental Health Guidelines Committee sponsored by the CFF and ECFS.

PMID- 25592659
TI  - Statins and brain integrity in older adults: secondary analysis of the Health ABC
      study.
AB  - INTRODUCTION: We examined whether statins are associated with better cerebral
      white (WM) and gray matter (GM) indices in community-dwelling elders. METHODS: In
      295 older adults, we compared white matter hyperintensities (WMH) on brain
      magnetic resonance imaging and, total WM fractional anisotropy (FA) and GM mean
      diffusivity (MD) on diffusion tensor imaging, of Alzheimer's disease (AD)
      relevant regions in statin-exposed and statin-unexposed participants stratified
      by Modified Mini-Mental Status Examination (3MS) score. RESULTS: There was no
      overall effect of statin exposure on cerebral structural indices. The interaction
      between statin exposure and 3MS was significant for total-WMH and WM FA (both P <
      .05) but not GM MD. In the lowest 3MS tertile (mean: 86), statin-exposed
      individuals had lower total-WMH and higher WM FA (P = .005 and P = .044) and FA
      of tracts linked to clinical AD (P-value range= .005-.04) despite statistical
      adjustments. These differences were not significant in the two higher 3MS
      tertiles. DISCUSSION: Statins may benefit WM in older adults vulnerable to
      dementia.

PMID- 25592660
TI  - Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium
      increases mediated by the P2Y1 and P2X7 receptors.
AB  - The P2X7 receptor (P2X7R) is a ligand-gated ion channel that conducts Na(+),
      K(+), and Ca(2+) when activated by extracellular ATP. In various cell types, such
      as secretory epithelia, the P2X7R is co-expressed with Ca(2+)-dependent Cl(-)
      channels of the TMEM16/anoctamin family. Here, we studied whether the P2X7R and
      TMEM16A/anoctamin-1 (Ano1) or TMEM16F/anoctamin-6 (Ano6) interact functionally
      and physically, using oocytes of Xenopus laevis and Ambystoma mexicanum (Axolotl)
      for heterologous expression. As a control, we co-expressed anoctamin-1 with the
      P2Y1 receptor (P2Y1R), which induces the release of Ca(2+) from intracellular
      stores via activating phospholipase C through coupling to Galphaq. We found that
      co-expression of anoctamin-1 with the P2Y1R resulted in a small transient
      increase in Cl(-) conductance in response to ATP. Co-expression of anoctamin-1
      with the P2X7R resulted in a large sustained increase in Cl(-) conductance via
      Ca(2+) influx through the ATP-opened P2X7R in Xenopus and in Axolotl oocytes,
      which lack endogenous Ca(2+)-dependent Cl(-) channels. P2Y1R- or P2X7R-mediated
      stimulation of Ano1 was primarily functional, as demonstrated by the absence of a
      physically stable interaction between Ano1 and the P2X7R. In the pancreatic cell
      line AsPC-1, we found the same functional Ca(2+)-dependent interaction of P2X7R
      and Ano1. The P2X7R-mediated sustained activation of Ano1 may be physiologically
      relevant to the time course of stimulus-secretion coupling in secretory
      epithelia. No such increase in Cl(-) conductance could be elicited by activating
      the P2X7 receptor in either Xenopus oocytes or Axolotl oocytes co-expressing
      Ano6. The lack of function of Ano6 can, at least in part, be explained by its
      poor cell-surface expression, resulting from a relatively inefficient exit of the
      homodimeric Ano6 from the endoplasmic reticulum.

PMID- 25592662
TI  - Endoscopic Mucosal Impedance Measurements Correlate With Eosinophilia and
      Dilation of Intercellular Spaces in Patients With Eosinophilic Esophagitis.
AB  - BACKGROUND & AIMS: Penetration of the esophageal epithelium by food antigens is
      an early event in the pathogenesis of eosinophilic esophagitis (EoE), but the
      precise relationship among eosinophilia, dilated intercellular spaces (DIS), and
      decreased barrier function is unclear. We investigated the correlation between
      site-specific mucosal impedance (MI) measurements of ion flux and esophageal
      histology, and whether MI measurements can be used to distinguish between
      patients with active and inactive EoE. METHODS: MI was measured (in Omega) in 10
      patients with active EoE (>15 eosinophils [eos]/high-power field [HPF]) and in 10
      with inactive EoE (<15 eos/HPF, as a result of treatment), and mucosal biopsy
      specimens were collected from 4 esophageal sites (2, 5, 10, and 15 cm above the Z
      line). MI also was measured in 10 individuals without esophageal symptoms
      (controls). MI measurements, eos/HPF, and DIS grade were compared among patients
      with EoE and controls. RESULTS: The esophageal MI values were significantly lower
      in patients with active EoE (1909 Omega) compared with inactive EoE (4349 Omega)
      or controls (5530 Omega) (P < .001). Biopsy specimens from 4 patients with active
      EoE contained fewer than 15 eos/HPF and lower-grade DIS than in patients with
      active disease. There were significant inverse correlations between MI and
      eos/HPF (rs = -.584), as well as between MI and DIS (rs = -.531; P < .001). The
      MI cut-off value of 2300 Omega identified patients with active EoE with 90%
      sensitivity and 91% specificity, and high-grade DIS with 89% sensitivity and 82%
      specificity. CONCLUSIONS: In patients with EoE, eosinophilia and DIS correlate
      with MI measurements of ion flux. Endoscopic MI measurement in the esophagus is
      safe and easy to perform, and can be used to assess activity of diseases such as
      EoE.

PMID- 25592661
TI  - Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study
      of Atherosclerosis.
AB  - BACKGROUND & AIMS: Levels of circulating of sex hormones are associated with
      glucose metabolism and adiposity, but little is known about their association
      with ectopic fat. We aimed to characterize the association between circulating
      sex hormones and liver fat. METHODS: We conducted a cross-sectional analysis by
      using data from the Multiethnic Study of Atherosclerosis to assess the
      association of the circulating levels of bioavailable testosterone, estradiol,
      dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver.
      Fatty liver was defined as a reduction of <=40 Hounsfield units, measured by
      computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old;
      white, black, Hispanic, or Chinese) at 6 centers in the United States. RESULTS:
      Women in the highest tertile of bioavailable testosterone were significantly more
      likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77;
      95% confidence interval, 1.07-2.92). We found an even greater difference for
      level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after
      adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and
      high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone
      replacement therapy use. Men in the highest tertile of estradiol level were
      significantly more likely to have fatty liver than men in the lowest tertile
      (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile
      of SHBG were less likely to have fatty liver than those in the lowest tertile
      (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations
      between hormone levels and fatty liver were not statistically significant.
      CONCLUSIONS: On the basis of a cross-sectional study, postmenopausal women with
      high levels of bioavailable testosterone are at greater risk for fatty liver. In
      men, higher levels of SHBG are associated with reduced risk for fatty liver.
      Higher levels of estradiol are associated with fatty liver in both sexes. This
      pattern is consistent with the sex-specific associations of sex hormones with
      other cardiometabolic risk factors.

PMID- 25592663
TI  - Elderly patients with colorectal cancer are oncologically undertreated.
AB  - AIMS: Colorectal cancer (CRC) is mainly a disease of the elderly. Our primary aim
      was to investigate if age had influence on treatment decisions in regards to
      surgery, referral to an oncologist and treatment by an oncologist. METHOD: We
      identified patients with CRC in our department from 2004 through 2011 in the
      Danish Colorectal Cancer Group (DCCG) database. According to age <=75 and >75
      years multivariate logistic regression analysis was used on treatment decisions:
      surgery, referral to an oncologist and oncologic treatment. Independent variables
      were age, ASA score, tumorlocation, stage, gender and year of diagnosis.
      Additional analysis was performed for stage III and IV patients as a subgroup.
      RESULTS: 1701 patients were included of which 525 were >75 years of age. In
      multivariate analysis there was no association between age and chance of surgery.
      Older patients had a significantly lower odds ratio for referral to an oncologist
      (OR 0.624, p < 0.0001) and for oncological treatment if referred (OR 0.218, p <
      0.0001). Being an elderly patient with stage III or IV CRC OR was 0.233 for
      referral- and for receiving treatment by an oncologist OR was 0.210 (p < 0.0001
      for both), after adjusting for possible confounders. CONCLUSION: Based on age
      elderly patients are on a lesser extent referred to an oncologist and get
      oncologic treatment less frequently. Surgically the elderly are not undertreated.

PMID- 25592665
TI  - A mild alkali treated jute fibre controlling the hydration behaviour of greener
      cement paste.
AB  - To reduce the antagonistic effect of jute fibre on the setting and hydration of
      jute reinforced cement, modified jute fibre reinforcement would be a unique
      approach. The present investigation deals with the effectiveness of mild alkali
      treated (0.5%) jute fibre on the setting and hydration behaviour of cement.
      Setting time measurement, hydration test and analytical characterizations of the
      hardened samples (viz., FTIR, XRD, DSC, TGA, and free lime estimation) were used
      to evaluate the effect of alkali treated jute fibre. From the hydration test, the
      time (t) required to reach maximum temperature for the hydration of control
      cement sample is estimated to be 860 min, whilst the time (t) is measured to be
      1040 min for the hydration of a raw jute reinforced cement sample. However, the
      time (t) is estimated to be 1020 min for the hydration of an alkali treated jute
      reinforced cement sample. Additionally, from the analytical characterizations, it
      is determined that fibre-cement compatibility is increased and hydration delaying
      effect is minimized by using alkali treated jute fibre as fibre reinforcement.
      Based on the analyses, a model has been proposed to explain the setting and
      hydration behaviour of alkali treated jute fibre reinforced cement composite.

PMID- 25592664
TI  - Review of ultrasound image guidance in external beam radiotherapy: I. Treatment
      planning and inter-fraction motion management.
AB  - In modern radiotherapy, verification of the treatment to ensure the target
      receives the prescribed dose and normal tissues are optimally spared has become
      essential. Several forms of image guidance are available for this purpose. The
      most commonly used forms of image guidance are based on kilovolt or megavolt x
      ray imaging. Image guidance can also be performed with non-harmful ultrasound
      (US) waves. This increasingly used technique has the potential to offer both
      anatomical and functional information.This review presents an overview of the
      historical and current use of two-dimensional and three-dimensional US imaging
      for treatment verification in radiotherapy. The US technology and the
      implementation in the radiotherapy workflow are described. The use of US guidance
      in the treatment planning process is discussed. The role of US technology in
      inter-fraction motion monitoring and management is explained, and clinical
      studies of applications in areas such as the pelvis, abdomen and breast are
      reviewed. A companion review paper (O'Shea et al 2015 Phys. Med. Biol. submitted)
      will extensively discuss the use of US imaging for intra-fraction motion
      quantification and novel applications of US technology to RT. 

PMID- 25592667
TI  - New titanium carbonyls: Ti2(CO)10, Ti2(CO)11, and Ti2(CO)12.
AB  - Structural and energetic features of the binuclear titanium carbonyls Ti2(CO)n (n
      = 12, 11, 10) have been examined using density functional theory. The lowest
      energy Ti2(CO)12 structure is a singlet structure consisting of two Ti(CO)6 units
      linked by Ti?Ti double bonds of lengths 3.0-3.2 A. A similar slightly higher
      energy triplet Ti2(CO)12 structure is found with longer Ti-Ti bonds (3.37-3.62
      A), considered to be formal single bonds. The energy required for the
      dissociation of Ti2(CO)12 into two Ti(CO)6 fragments is 18.5 +/- 2 kcal/mol
      higher than the energy required for the dissociation of V2(CO)12 into two V(CO)6
      fragments. For the unsaturated Ti2(CO)11 system, the lowest-energy structures
      contain a four-electron-donor bridging eta(2)-MU-CO group and 10 terminal CO
      groups with formal Ti?Ti double bonds in the singlet structures and formal Ti-Ti
      single bonds in the triplet structures. Similarly, the most favored geometries
      for the more highly unsaturated Ti2(CO)10 contain two four-electron-donor
      bridging eta(2)-MU-CO groups with formal Ti?Ti double bonds for the singlet
      structures and formal Ti-Ti single bonds for the triplet structures. Higher
      energy triplet Ti2(CO)10 structures are found with two or three two-electron
      donor semibridging CO groups and formal Ti=Ti triple bonds of length 2.7-2.8 A. 

PMID- 25592666
TI  - Cross-Sectional Study of 24-Hour Urinary Electrolyte Excretion and Associated
      Health Outcomes in a Convenience Sample of Australian Primary Schoolchildren: The
      Salt and Other Nutrients in Children (SONIC) Study Protocol.
AB  - BACKGROUND: Dietary sodium and potassium are involved in the pathogenesis of
      cardiovascular disease. Data exploring the cardiovascular outcomes associated
      with these electrolytes within Australian children is sparse. Furthermore, an
      objective measure of sodium and potassium intake within this group is lacking.
      OBJECTIVE: The primary aim of the Salt and Other Nutrient Intakes in Children
      ("SONIC") study was to measure sodium and potassium intakes in a sample of
      primary schoolchildren located in Victoria, Australia, using 24-hour urine
      collections. Secondary aims were to identify the dietary sources of sodium and
      potassium, examine the association between these electrolytes and cardiovascular
      risk factors, and assess children's taste preferences and saltiness perception of
      manufactured foods. METHODS: A cross-sectional study was conducted in a
      convenience sample of schoolchildren attending primary schools in Victoria,
      Australia. Participants completed one 24-hour urine collection, which was
      analyzed for sodium, potassium, and creatinine. Completeness of collections was
      assessed using collection time, total volume, and urinary creatinine. One 24-hour
      dietary recall was completed to assess dietary intake. Other data collected
      included blood pressure, body weight, height, waist and hip circumference.
      Children were also presented with high and low sodium variants of food products
      and asked to discriminate salt level and choose their preferred variant. Parents
      provided demographic information and information on use of discretionary salt.
      Descriptive statistics will be used to describe sodium and potassium intakes.
      Linear and logistic regression models with clustered robust standard errors will
      be used to assess the association between electrolyte intake and health outcomes
      (blood pressure and body mass index/BMI z-score and waist circumference) and to
      assess differences in taste preference and discrimination between high and low
      sodium foods, and correlations between preference, sodium intake, and covariates.
      RESULTS: A total of 780 children across 43 schools participated. The results from
      this study are expected at the end of 2015. CONCLUSIONS: This study will provide
      the first objective measure of sodium and potassium intake in Australian
      schoolchildren and improve our understanding of the relationship of these
      electrolytes to cardiovascular risk factors. Furthermore, this study will provide
      insight into child taste preferences and explore related factors. Given the
      cardiovascular implications of consuming too much sodium and too little
      potassium, monitoring of these nutrients during childhood is an important public
      health initiative.

PMID- 25592669
TI  - Septic vasculitis and vasculopathy in some infectious emergencies: the
      perspective of the histopathologist.
AB  - Sepsis is a potentially life-threatening complication of an infection where
      cutaneous lesions often represent one of the early signs. A myriad of
      microorganisms including bacteria, fungi, yeasts, viruses, protozoas, helminths
      and algae can be implicated. A broad spectrum of clinical and histopathologic
      findings can be observed in the skin and the common denominator is a thrombotic
      vasculopathy. The pathogenesis of cutaneous septic vasculitis (SV)/vasculopathy
      is complex and includes five main mechanisms: disseminated intravascular
      coagulation, direct invasion and occlusion of blood vessel walls by
      microorganisms, hypersensitivity reaction with immune complex deposition into
      blood vessel walls, embolism from a distant infectious site and vascular effects
      of toxins. Herein we describe the clinicopathologic findings of some selected
      cases of SV recently observed in our hospital, including purpura fulminans,
      necrotizing fasciitis, cutaneous meningococcemia, malignant syphilis and
      disseminated alternaria infection. Histopathologically, a wide spectrum of
      histopathologic changes was observed in skin specimens from the various entities,
      involving the intensity and composition of the inflammatory infiltrate, the
      degree of vascular changes and the presence of microorganisms, that ranged from a
      predominant not inflammatory, thrombotic-occlusive vasculopathy in purpura
      fulminans to leukocytoclastic vasculitis like changes in cutaneous
      meningococcemia to a dermal angiomatosis-like pattern in disseminated Alternaria
      infection. The different pathologic presentations may be related to the
      microorganism involved, the main pathogenetic mechanism that induced the vascular
      injury and the individual immunologic burden. Early skin biopsy for
      histopathologic examination and microbiologic culture is a cornerstone in the
      diagnosis of life-threatening diseases that present with cutaneous septic
      vasculitis. Ancillary techniques, such as immunohistochemistry and polymerase
      chain reaction are additional novel and helpful tools to identify pathogens,
      leading to definite diagnosis in cases with challenging or ambiguous clinical
      and/or pathologic findings. 

PMID- 25592668
TI  - Health-Related Quality of Life among Children and Adolescents during
      Hematopoietic Stem Cell Transplant Recovery.
AB  - Health-related quality of life (HRQoL) has been noted to fluctuate among children
      during hematopoietic stem cell transplant (HSCT) recovery; however, the specific
      timing and associations of these changes are poorly understood. This repeated
      measures study aimed to describe HRQoL changes among children and adolescents
      during the first 6 months of HSCT recovery and estimate the associations of
      demographic factors, diagnosis, transplant information, and symptoms with HRQoL.
      Twenty-three children and adolescents who received an allogeneic HSCT were
      recruited from a pediatric teaching institution in the southern United States.
      Demographic, diagnosis, and transplant information was obtained from the medical
      record. The Memorial Symptom Assessment questionnaire and the Peds Quality of
      Life Cancer Module (PedsQL CM) were completed at 1 month post-HSCT and then once
      monthly for 5 additional months. Mean HRQoL scores fluctuated during the study
      with the lowest mean HRQoL noted at 1 month post-HSCT and the highest mean HRQoL
      noted at 4 months post-HSCT. No significant differences in HRQoL scores were
      noted among demographic, diagnosis, or transplant factors. Feeling tired, sad, or
      worried or having insomnia at 1 month post-HSCT was negatively correlated to
      HRQoL. Nurses have opportunities to explore important issues with patients and
      need to be aware of fluctuations with HRQoL and factors associated with lower
      HRQoL during HSCT recovery.

PMID- 25592670
TI  - Chronic localized leukocytoclastic vasculitis: clinicopathological spectrum of
      granuloma faciale with and without extrafacial and mucosal involvement.
AB  - Granuloma faciale (GF) is a rare cutaneous condition of unknown origin, that
      usually presents as one or more brown-purple papules, plaques and/or nodules,
      localized mostly on the face, although extrafacial lesions can also occur.
      Eosinophilic angiocentric fibrosis (EAF) is regarded as the mucosal counterpart
      of GF. Histologically, it has been described as a persistent leukocytoclastic
      vasculitis, with a dense polymorphous inflammatory infiltrate in the superficial
      and mid dermis, typically sparing the subpapillary dermis, the so called grenz
      zone. The presence of eosinophils is considered a characteristic feature of the
      disease. All the cases of GF seen at the Dermatology Unit from 2002 to 2013 were
      considered and reviewed, both clinically and histopathologically. Only cases with
      consistent clinical findings of GF, and accurate patient's history were
      considered. Ten cases of GF were reviewed for both histological specificity and
      clinico-pathological correlation. Two patients presented extrafacial lesions. One
      patient had involvement of nasal mucosa. Two patients suffered from associated
      rheumatological diseases. The most frequent histopathologic features were the
      presence of a grenz zone and eosinophils in the infiltrate, but also adnexal
      involvement was often present; vascular changes were constant, yet
      leukocytoclastic vasculitis could be recorded only in four cases. Fibrosis or
      sclerosis were always absent. Clinical pictures of the patients treated
      demonstrated a complete remission of the lesions, without scarring. However, a
      complete enduring healing was observed only in two patients, and relapse or
      incomplete remission of the disease was the rule. In conclusion a review of
      clinicopathological findings of ten patients affected by GF was made and new
      details of the disease presented. 

PMID- 25592671
TI  - Body image and awareness in patients with advanced-stage melanoma.
AB  - BACKGROUND: Body image (BI) is a very important aspect to be taken care of,
      especially in cancer patients. METHODS: We administered the Body Image Scales,
      with a specifically created semi-structured questionnaire which includes items
      that investigate the level of awareness and the degree of acceptance of the
      disease of the patient, was administered to patients giving their written
      informed consent to participate to the study. RESULTS: The results show that our
      population sample got an average score of 17.25 showing precisely problems
      related to body image. CONCLUSIONS: An adequate psychological support is crucial,
      as it has been widely demonstrated that body-image-related issues have a negative
      impact on patients' quality of life, especially in the oncology field. Such
      support has the aim of dealing with those aspects which can compromise the
      patients' equilibrium and quality of life.

PMID- 25592672
TI  - Who and how to screen for cancer in at-risk inflammatory bowel disease patients.
AB  - Inflammatory bowel diseases (IBDs) include both Crohn's disease and ulcerative
      colitis and both diseases are marked by inflammation within the gastrointestinal
      tract. Due to long-standing inflammation, IBD patients are at increased risk of
      colorectal cancer, especially patients with chronic inflammation, pancolitis, co
      diagnosis of primary sclerosing cholangitis and a longer duration of disease.
      Small bowel inflammation places Crohn's patients at an increased risk of small
      bowel cancer. A higher risk of skin cancers, lymphomas and cervical abnormalities
      is also seen in IBD patients; this is likely related to both disease factors and
      the presence of immunosuppressive medication. This article reviews which patients
      are at an increased risk of IBD-associated or IBD treatment-associated cancers,
      when to begin screening and which screening methods are recommended. 

PMID- 25592673
TI  - Anti-estrogen-resistant breast cancer cells are sensitive to cisplatin plus TRAIL
      treatment.
AB  - Breast cancer patients who are positive for estrogen receptor (ER) are usually
      treated with anti-estrogen drugs, such as tamoxifen (Tam). However, a great
      majority of such patients eventually develop resistance to Tam. In this study,
      MCF-7 cells (with de novo and/or acquired resistance to Tam) as well as T47D
      cells (acquired resistance to Tam) models were used to investigate the effect of
      treatment with cisplatin plus tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL). The results in the two cell types treated with cisplatin plus
      TRAIL showed significantly increased cell death compared to that in the untreated
      control cells. A similar treatment had a minimal effect on normal breast cells,
      the increased cell death appeared to be caused by the activation of caspases and,
      inhibition of the activity of caspases (using relatively specific inhibitors)
      reduced the cell death caused by cisplatin plus TRAIL treatment. Taken together,
      the results suggested that cisplatin plus TRAIL treatment has the potential to
      provide a novel treatment strategy to improve the treatment outcome in anti
      estrogen-resistant breast cancer patients.

PMID- 25592674
TI  - Electrophysiological Features of Neurons in the Mesencephalic Trigeminal Nuclei.
AB  - Mesencephalic trigeminal nucleus (Mes V) neurons represent an uncommon class of
      primary sensory neurons. Besides receiving somatosensory information, Mes V
      neurons are also involved in regulating multisensory information. The present
      review first describes the passive features as well as three important currents,
      followed by a distinct excitability classification and a description of the
      excitability transition of Mes V neurons. Furthermore, their resonance property,
      the existence of membrane oscillation and electrical coupling which may promote
      strong synchronization, as well as their function in controlling stretch reflex
      activity, are discussed.

PMID- 25592676
TI  - Remembering, imagining, false memories & personal meanings.
AB  - The Self-Memory System encompasses the working self, autobiographical memory and
      episodic memory. Specific autobiographical memories are patterns of activation
      over knowledge structures in autobiographical and episodic memory brought about
      by the activating effect of cues. The working self can elaborate cues based on
      the knowledge they initially activate and so control the construction of memories
      of the past and the future. It is proposed that such construction takes place in
      the remembering-imagining system - a window of highly accessible recent memories
      and simulations of near future events. How this malfunctions in various disorders
      is considered as are the implication of what we term the modern view of human
      memory for notions of memory accuracy. We show how all memories are to some
      degree false and that the main role of memories lies in generating personal
      meanings. 

PMID- 25592675
TI  - Biomedical question answering using semantic relations.
AB  - BACKGROUND: The proliferation of the scientific literature in the field of
      biomedicine makes it difficult to keep abreast of current knowledge, even for
      domain experts. While general Web search engines and specialized information
      retrieval (IR) systems have made important strides in recent decades, the problem
      of accurate knowledge extraction from the biomedical literature is far from
      solved. Classical IR systems usually return a list of documents that have to be
      read by the user to extract relevant information. This tedious and time-consuming
      work can be lessened with automatic Question Answering (QA) systems, which aim to
      provide users with direct and precise answers to their questions. In this work we
      propose a novel methodology for QA based on semantic relations extracted from the
      biomedical literature. RESULTS: We extracted semantic relations with the SemRep
      natural language processing system from 122,421,765 sentences, which came from
      21,014,382 MEDLINE citations (i.e., the complete MEDLINE distribution up to the
      end of 2012). A total of 58,879,300 semantic relation instances were extracted
      and organized in a relational database. The QA process is implemented as a search
      in this database, which is accessed through a Web-based application, called SemBT
      (available at http://sembt.mf.uni-lj.si ). We conducted an extensive evaluation
      of the proposed methodology in order to estimate the accuracy of extracting a
      particular semantic relation from a particular sentence. Evaluation was performed
      by 80 domain experts. In total 7,510 semantic relation instances belonging to
      2,675 distinct relations were evaluated 12,083 times. The instances were
      evaluated as correct 8,228 times (68%). CONCLUSIONS: In this work we propose an
      innovative methodology for biomedical QA. The system is implemented as a Web
      based application that is able to provide precise answers to a wide range of
      questions. A typical question is answered within a few seconds. The tool has some
      extensions that make it especially useful for interpretation of DNA microarray
      results.

PMID- 25592677
TI  - Porous coordination polymers with ubiquitous and biocompatible metals and a
      neutral bridging ligand.
AB  - The design of inexpensive and less toxic porous coordination polymers (PCPs) that
      show selective adsorption or high adsorption capacity is a critical issue in
      research on applicable porous materials. Although use of Group II magnesium(II)
      and calcium(II) ions as building blocks could provide cheaper materials and lead
      to enhanced biocompatibility, examples of magnesium(II) and calcium(II) PCPs are
      extremely limited compared with commonly used transition metal ones, because
      neutral bridging ligands have not been available for magnesium(II) and
      calcium(II) ions. Here we report a rationally designed neutral and charge
      polarized bridging ligand as a new partner for magnesium(II) and calcium(II)
      ions. The three-dimensional magnesium(II) and calcium(II) PCPs synthesized using
      such a neutral ligand are stable and show selective adsorption and separation of
      carbon dioxide over methane at ambient temperature. This synthetic approach
      allows the structural diversification of Group II magnesium(II) and calcium(II)
      PCPs. 

PMID- 25592679
TI  - Risk factors for gastroenteritis in child day care.
AB  - The child day-care centre (DCC) is often considered as one risk factor for
      gastroenteritis (GE) rather than a complex setting in which the interplay of many
      factors may influence the epidemiology of GE. This study aimed to identify DCC
      level risk factors for GE and major enteropathogen occurrence. A dynamic network
      of 100 and 43 DCCs participated in a syndromic and microbiological surveillance
      during 2010-2013. The weekly incidence of GE events and weekly prevalence of five
      major enteropathogens (rotavirus, norovirus, astrovirus, Giardia lamblia,
      Cryptosporidium hominis/parvum) were modelled per DCC using mixed-effects
      negative binomial/Poisson regression models. Sixteen hundred children were
      surveyed up to 3 years, during which 1829 GE episodes were reported and 5197
      faecal samples were analysed. Identified risk factors were: large DCC capacity,
      crowding, having animals, nappy changing areas, sandpits, paddling pools,
      cleaning potties in normal sinks, cleaning vomit with paper towels (but without
      cleaner), mixing of staff between child groups, and staff members with multiple
      daily duties. Protective factors were: disinfecting fomites with chlorine,
      cleaning vomit with paper towels (and cleaner), daily cleaning of bed linen/toys,
      cohorting and exclusion policies for ill children and staff. Targeting these
      factors may reduce the burden of DCC-related GE. 

PMID- 25592678
TI  - Inhibition of oxidative phosphorylation for enhancing citric acid production by
      Aspergillus niger.
AB  - BACKGROUND: The spore germination rate and growth characteristics were compared
      between the citric acid high-yield strain Aspergillus niger CGMCC 5751 and A.
      niger ATCC 1015 in media containing antimycin A or DNP. We inferred that
      differences in citric acid yield might be due to differences in energy metabolism
      between these strains. To explore the impact of energy metabolism on citric acid
      production, the changes in intracellular ATP, NADH and NADH/NAD+ were measured at
      various fermentation stages. In addition, the effects of antimycin A or DNP on
      energy metabolism and citric acid production was investigated by CGMCC 5751.
      RESULTS: By comparing the spore germination rate and the extent of growth on PDA
      plates containing antimycin A or DNP, CGMCC 5751 was shown to be more sensitive
      to antimycin A than ATCC 1015. The substrate-level phosphorylation of CGMCC 5751
      was greater than that of ATCC 1015 on PDA plates with DNP. DNP at tested
      concentrations had no apparent effect on the growth of CGMCC 5751. There were no
      apparent effects on the mycelial morphology, the growth of mycelial pellets or
      the dry cell mass when 0.2 mg L(-1) antimycin A or 0.1 mg L(-1) DNP was added to
      medium at the 24-h time point. The concentrations of intracellular ATP, NADH and
      NADH/NAD+ of CGMCC 5751 were notably lower than those of ATCC 1015 at several
      fermentation stages. Moreover, at 96 h of fermentation, the citric acid
      production of CGMCC 5751 reached up to 151.67 g L(-1) and 135.78 g L(-1) by
      adding 0.2 mg L(-1) antimycin A or 0.1 mg L(-1) DNP, respectively, at the 24-h
      time point of fermentation. Thus, the citric acid production of CGMCC 5751 was
      increased by 19.89% and 7.32%, respectively. CONCLUSIONS: The concentrations of
      intracellular ATP, NADH and NADH/NAD+ of the citric acid high-yield strain CGMCC
      5751 were notably lower than those of ATCC 1015. The excessive ATP has a strong
      inhibitory effect on citric acid accumulation by A. niger. Increasing NADH
      oxidation and appropriately reducing the concentration of intracellular ATP can
      accelerate glycolysis and the TCA cycle to enhance citric acid yield.

PMID- 25592681
TI  - Stable isotope labeling strategy for curcumin metabolite study in human liver
      microsomes by liquid chromatography-tandem mass spectrometry.
AB  - The identification of drug metabolites is very important in drug development.
      Nowadays, the most widely used methods are isotopes and mass spectrometry.
      However, the commercial isotopic labeled reagents are usually very expensive, and
      the rapid and convenient identification of metabolites is still difficult. In
      this paper, an (18)O isotope labeling strategy was developed and the isotopes
      were used as a tool to identify drug metabolites using mass spectrometry.
      Curcumin was selected as a model drug to evaluate the established method, and the
      (18)O labeled curcumin was successfully synthesized. The non-labeled and (18)O
      labeled curcumin were simultaneously metabolized in human liver microsomes (HLMs)
      and analyzed by liquid chromatography/mass spectrometry (LC-MS). The two groups
      of chromatograms obtained from metabolic reaction mixture with and without
      cofactors were compared and analyzed using Metabolynx software (Waters Corp.,
      Milford, MA, USA). The mass spectra of the newly appearing chromatographic peaks
      in the experimental sample were further analyzed to find the metabolite
      candidates. Their chemical structures were confirmed by tandem mass spectrometry.
      Three metabolites, including two reduction products and a glucuronide conjugate,
      were successfully detected under their specific HLMs metabolic conditions, which
      were in accordance with the literature reported results. The results demonstrated
      that the developed isotope labeling method, together with post-acquisition data
      processing using Metabolynx software, could be used for fast identification of
      new drug metabolites. 

PMID- 25592682
TI  - Immature platelet fraction values predict recovery of platelet counts following
      liver transplantation.
AB  - BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a
      well-recognized and prevalent early postoperative complication. In the current
      study, we assessed the clinical utility of the immature platelet fraction
      (expressed as a percent of total platelets, IPF %) to predict platelet count
      recovery following OLT. METHODS: We analyzed the changes in peripheral platelet
      counts, IPF values, and liver function before OLT, and 21 days after
      transplantation in 30 patients with liver cirrhosis. All patients were followed
      up for at least six months. RESULTS: The nadir in the peripheral platelet counts
      most commonly occurred on the 5th day after post-transplant. Platelets counts
      gradually rose again to exceed pre-transplant levels by the 3rd to 4th day after
      the IPF % reached its peak. CONCLUSION: The IPF % increased prior to the
      elevation of platelet counts in patients with OLT suggesting that the IPF % may
      reflect production of platelets. These findings suggest IPF% could be useful as a
      predictor of platelet recovery in patients with OLT.

PMID- 25592683
TI  - Impact of valve surgery on serum osteopontin levels in patients with mitral
      regurgitation.
AB  - OBJECTIVE: Osteopontin (OPN), a sialoprotein present within atherosclerotic
      lesions, especially in calcified plaques, is linked to the progression of
      coronary artery disease and heart failure. We assessed the impact of valve
      surgery on serum OPN and left ventricular (LV) function in patients with mitral
      regurgitation (MR). METHODS: Thirty-two patients with severe MR scheduled for
      surgery were included in the study. Echocardiography markers were assessed
      preoperatively and at 3 months following the surgery and matched with the serum
      OPN levels. RESULTS: Valve surgery was associated with a reduction of the
      ejection fraction (EF) from 55.2 +/- 6.3 to 48.8 +/- 7.1% after surgery, p <
      0.001. Following surgery, the OPN level was significantly higher than
      preoperatively (mean 245, range 36-2,284 ng/ml vs. 76, 6-486 ng/ml, p = 0.007).
      Preoperative OPN exhibited a slight negative correlation with the EF (r = -0.35,
      p = 0.04), and a moderate correlation with vena contracta (r = -0.38, p = 0.02).
      There were no other meaningful correlations between conventional
      echocardiographic parameters and OPN. CONCLUSION: Following valve surgery due to
      severe MR, patients exhibited a decrease in EF and an increase in OPN levels. The
      assessment of preoperative OPN failed to strongly predict probable LV
      dysfunction.

PMID- 25592680
TI  - Kappa opioid receptor signaling in the brain: Circuitry and implications for
      treatment.
AB  - Kappa opioid receptors (KORs) in the central nervous system have been known to be
      important regulators of a variety of psychiatry illnesses, including anxiety and
      addiction, but their precise involvement in these disorders is complex and has
      yet to be fully elucidated. Here, we briefly review the pharmacology of KORs in
      the brain, including KOR's involvement in anxiety, depression, and drug
      addiction. We also review the known neuronal circuitry impacted by KOR signaling,
      and interactions with corticotrophin-releasing factor (CRF), another key peptide
      in anxiety-related illnesses, as well as the role of glucocorticoids. We suggest
      that KORs are a promising therapeutic target for a host of neuropsychiatric
      conditions. 

PMID- 25592684
TI  - Molecular mechanism for opioid dichotomy: bidirectional effect of MU-opioid
      receptors on P2X3 receptor currents in rat sensory neurones.
AB  - Here, we describe a molecular switch associated with opioid receptors-linked
      signalling cascades that provides a dual opioid control over P2X3 purinoceptor in
      sensory neurones. Leu-enkephalin inhibited P2X3-mediated currents with IC50 ~10
      nM in ~25% of small nociceptive rat dorsal root ganglion (DRG) neurones. In
      contrast, in neurones pretreated with pertussis toxin leu-enkephalin produced
      stable and significant increase of P2X3 currents. All effects of opioid were
      abolished by selective MU-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr
      Pen-Thr-NH2 (CTOP), nonselective inhibitor naloxone, and by PLC inhibitor U73122.
      Thus, we discovered a dual link between purinoceptors and MU-opioid receptors:
      the latter exert both inhibitory (pertussis toxin-sensitive) and stimulatory
      (pertussis toxin-insensitive) actions on P2X3 receptors through phospholipase C
      (PLC)-dependent pathways. This dual opioid control of P2X3 receptors may provide
      a molecular explanation for dichotomy of opioid therapy. Pharmacological control
      of this newly identified facilitation/inhibition switch may open new perspectives
      for the adequate medical use of opioids, the most powerful pain-killing agents
      known today.

PMID- 25592685
TI  - The treatment of autism with low-dose phenytoin: a case report.
AB  - INTRODUCTION: The drug treatment of autism spectrum disorders is often poorly
      tolerated and has traditionally targeted associated conditions (such as
      inattention or irritability) that frequently coexist, with limited benefit for
      the core social deficits. Here, I describe the novel use of a low dose of the
      anti-epileptic phenytoin to enhance social functioning in a patient with an
      autism spectrum disorder. CASE PRESENTATION: I present the case of a 19-year-old
      Caucasian man with autism spectrum disorder treated with stimulant medication
      since early childhood. He experienced long-standing difficulties in establishing
      and maintaining relationships and reading social cues, and was socially isolated.
      Within 10 minutes of a single sublingual low dose of phenytoin there was an
      immediate observable improvement in his eye contact and integration of both
      verbal and non-verbal communication. This enhanced social functioning associated
      with his adherence to the low-dose phenytoin therapy was maintained for over 18
      months of follow-up. These clinical observations were supported by ratings using
      the Autism-Spectrum Quotient and the Depression, Anxiety and Stress Scales,
      recorded pre-treatment and after seven months on 5mg phenytoin. CONCLUSION: This
      case report provides the first potential evidence that a low dose of phenytoin, a
      widely used and well tolerated anti-epileptic medication, may be capable of
      modifying the core social cognitive deficits associated with autism spectrum
      disorders. While acknowledging this is a single case study, the lack of
      availability of safe and effective treatments to address the important core
      deficits associated with autism spectrum disorders makes this case noteworthy.

PMID- 25592686
TI  - The impact of complaints procedures on the welfare, health and clinical practise
      of 7926 doctors in the UK: a cross-sectional survey.
AB  - OBJECTIVES: The primary aim was to investigate the impact of complaints on
      doctors' psychological welfare and health. The secondary aim was to assess
      whether doctors report exposure to a complaints process is associated with
      defensive medical practise. DESIGN: This was a cross-sectional anonymous survey
      study. Participants were stratified into recent/current, past, no complaints.
      Each group completed tailored versions of the survey. PARTICIPANTS: 95 636
      doctors were invited to participate. A total of 10 930(11.4%) responded, 7926
      (8.3%) completed the full survey and were included in the complete analysis. MAIN
      OUTCOME MEASURES: Anxiety and depression were assessed using the standardised
      Generalised Anxiety Disorder scale and Physical Health Questionnaire. Defensive
      practise was evaluated using a new measure. Single-item questions measured stress
      related illnesses, complaints-related experience, attitudes towards complaints
      and views on improving complaints processes. RESULTS: 16.9% of doctors with
      current/recent complaints reported moderate/severe depression (relative risk (RR)
      1.77 (95% CI 1.48 to 2.13) compared to doctors with no complaints (9.5%)).
      Fifteen per cent reported moderate/severe anxiety (RR=2.08 (95% CI 1.61 to 2.68)
      compared to doctors with no complaints (7.3%)). Distress increased with complaint
      severity, with highest levels after General Medical Council (GMC) referral (26.3%
      depression, 22.3% anxiety). Doctors with current/recent complaints were 2.08 (95%
      CI 1.61 to 2.68) times more likely to report thoughts of self-harm or suicidal
      ideation. Most doctors reported defensive practise: 82-89% hedging and 46-50%
      avoidance. Twenty per cent felt victimised after whistleblowing, 38% felt
      bullied, 27% spent over 1 month off work. Over 80% felt processes would improve
      with transparency, managerial competence, capacity to claim lost earnings and
      action against vexatious complainants. CONCLUSIONS: Doctors with recent/current
      complaints have significant risks of moderate/severe depression, anxiety and
      suicidal ideation. Morbidity was greatest in cases involving the GMC. Most
      doctors reported practising defensively, including avoidance of procedures and
      high-risk patients. Many felt victimised as whistleblowers or reported bullying.
      Suggestions to improve complaints processes included transparency and managerial
      competence.

PMID- 25592687
TI  - A mutational and expressional analysis of DNMT3A in acute myeloid leukemia
      cytogenetic subgroups.
AB  - OBJECTIVES: Despite numerous studies in order to determine the allele frequency
      and clinical impact of DNA methyltransferase 3 A (DNMT3A) gene mutations in acute
      myeloid leukemia (AML), reports about the expression analysis of this gene are
      rare and between the available, differences are evident. METHODS: In this study,
      we decided to investigate DNMT3A possible expression changes with regard to their
      mutation and cytogenetic status in a series of 96 AML patients. RESULTS:
      Mutations were founded in 17 of the 96 patients (17.7%) and associated with
      higher age and white blood cell count (P < 0.001). Our mutants have had shorter
      overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P = 0.011)
      than those without. Multivariate analysis showed that DNMT3A mutation is an
      independent prognostic indicator for OS and RFS (P < 0.001). In relation to
      expression results, we had over and under expression for our favorable and
      unfavorable cytogenetic subgroups, respectively (P = 0.005 and P < 0.001,
      respectively). In intermediate subgroup, total DNMT3A expression did not alter (P
      = 0.575). Interestingly, we noticed similar expression results for DNMT3A
      transcript 2, to that of the total. DISCUSSION AND CONCLUSION: In relation to
      DNMT3A expression, from the perspective of diagnostic application and its
      biological significance, it is difficult to accept its primacy over cytogenetic
      value in favorable and unfavorable subgroups and if so, we did not address this
      issue in our study due to sample size limitation. In intermediate subgroup,
      particularly in normal karyotype-AML, given the lack of convincing results, it
      seems unlikely that DNMT3A expression analysis could attract attention in
      diagnostic workup and risk prediction of AML.

PMID- 25592688
TI  - What evidence for the benefits of '5-a-day', a Mediterranean diet and sodium
      restriction on health?
AB  - Guidelines for healthcare professionals encourage the provision of dietary advice
      to promote healthy eating, especially to patients at risk of chronic disease.1
      Yet the evidence base for dietary interventions relies heavily on epidemiological
      studies, which are subject to the challenges associated with observational
      research. Such problems include difficulties of assessing and measuring outcomes,
      misclassification, confounding and establishing causation. This reliance on
      epidemiological evidence may reflect the difficulty and cost of carrying out
      large-scale long-term randomised controlled studies of diet.2 In addition, there
      is a dearth of organisations willing to fund such research. Recent publications
      have questioned the '5-a-day' advice for fruit and vegetable consumption and
      population-level attempts to lower salt consumption.3,4 Studies of lifestyle
      advice are widely reported in the media, which may lead to public confusion about
      dietary advice when conclusions differ. Some researchers have urged a move from
      assessing how single foods or nutrients affect risk factors, to a consideration
      of the overall diet pattern, as this may overcome the risk of confounding the
      effect of one food type by others in the diet.5 The Mediterranean diet pattern is
      one of the most studied, since its identification in the late 1970s. Here, we
      provide an update of evidence for three aspects of dietary recommendations that
      feature regularly in the media-fruit and vegetable intake, salt reduction and the
      Mediterranean diet. 

PMID- 25592689
TI  - ?Jaydess IUS.
AB  - In the UK, around 75% of women of reproductive age use some form of
      contraception.1 Although combined oral contraceptives and barrier contraception
      are the most widely used, their effectiveness is dependent on their correct and
      consistent use. In contrast, long-acting reversible contraceptives provide
      effective and reliable methods of contraception that are not reliant upon user
      adherence.2 ?Jaydess (Bayer) is a new long-acting reversible levonorgestrel
      releasing intra-uterine delivery system (IUS) that provides contraception for up
      to 3 years.3 It was launched in April 2014, and is the second levonorgestrel IUS
      available in the UK. Here we discuss the evidence for its effectiveness and
      safety, and consider its place in therapy. 

PMID- 25592690
TI  - Understanding acute kidney injury in low resource settings: a step forward.
AB  - Attention has recently been focused on addressing the problem of acute kidney
      injury in both the developed and developing world. Little information is actually
      available on the incidence and management of AKI in low resource settings. Thus,
      the paper by Bagasha in the current issue of BMC Nephrology makes an important
      contribution to our understanding of this serious and potentially remediable
      problem. 

PMID- 25592692
TI  - Diagnostic coronary angiography is getting old!

PMID- 25592691
TI  - Atherosclerotic plaque characteristics by CT angiography identify coronary
      lesions that cause ischemia: a direct comparison to fractional flow reserve.
AB  - OBJECTIVES: This study evaluated the association between atherosclerotic plaque
      characteristics (APCs) by coronary computed tomographic angiography (CTA), and
      lesion ischemia by fractional flow reserve (FFR). BACKGROUND: FFR is the gold
      standard for determining lesion ischemia. Although APCs by CTA-including
      aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation
      plaque (LAP), and spotty calcification (SC)-are associated with future coronary
      syndromes, their relationship to lesion ischemia is unclear. METHODS: 252
      patients (17 centers, 5 countries; mean age 63 years; 71% males) underwent
      coronary CTA, with FFR performed for 407 coronary lesions. Coronary CTA was
      interpreted for <50% and >=50% stenosis, with the latter considered obstructive.
      APCs by coronary CTA were defined as: 1) PR, lesion diameter/reference diameter
      >1.10; 2) LAP, any voxel <30 Hounsfield units; and 3) SC, nodular calcified
      plaque <3 mm. Odds ratios (OR) and net reclassification improvement of APCs for
      lesion ischemia, defined by FFR <=0.8, were analyzed. RESULTS: By FFR, ischemia
      was present in 151 lesions (37%). %APV was associated with a 50% increased risk
      of ischemia per 5% additional APV. PR, LAP, and SC were associated with ischemia,
      with a 3 to 5 times higher prevalence than in nonischemic lesions. In
      multivariable analyses, a stepwise increased risk of ischemia was observed for 1
      (OR: 4.0, p < 0.001) and >=2 (OR: 12.1, p < 0.001) APCs. These findings were APC
      dependent, with PR (OR: 5.3, p < 0.001) and LAP (OR: 2.1, p = 0.038) associated
      with ischemia, but not SC. When examined by stenosis severity, PR remained a
      predictor of ischemia for all lesions, whereas %APV and LAP were associated with
      ischemia for only >=50%, but not for <50%, stenosis. CONCLUSIONS: %APV and APCs
      by coronary CTA improve identification of coronary lesions that cause ischemia.
      PR is associated with all ischemia-causing lesions, whereas %APV and LAP are only
      associated with ischemia-causing lesions >=50%. (Determination of Fractional Flow
      Reserve by Anatomic Computed Tomographic Angiography; NCT01233518).

PMID- 25592693
TI  - Valve regurgitation with LV dysfunction: how did we get there?

PMID- 25592694
TI  - Lipoprotein-associated phospholipase A2 and aortic stenosis: biomarker or new
      target for an old foe?

PMID- 25592695
TI  - Myocardial T1: the rise of a novel biomarker continues.

PMID- 25592696
TI  - Developing imaging biomarkers for myocardial involvement in amyloidosis:
      challenge and opportunity.

PMID- 25592697
TI  - OCT imaging of macrophages: a bright spot in the study of inflammation in human
      atherosclerosis.

PMID- 25592699
TI  - Pulmonary hypertension in valvular disease: a comprehensive review on
      pathophysiology to therapy from the HAVEC Group.
AB  - Pulmonary hypertension (PH) is a classic pathophysiological consequence of left
      sided valvular heart disease (VHD). However, as opposed to other forms of PH,
      there are relatively few published data on the prevalence, impact on outcome, and
      management of PH with VHD. The objective of this paper is to present a systematic
      review of PH in patients with VHD. PH is found in 15% to 60% of patients with VHD
      and is more frequent among symptomatic patients. PH is associated with higher
      risk of cardiac events under conservative management, during valve replacement or
      repair procedures, and even following successful corrective procedures. In
      addition to its usefulness in assessing the presence and severity of VHD, Doppler
      echocardiography is a key tool in diagnosis of PH and assessment of its
      repercussion on right ventricular function. Assessment of pulmonary arterial
      pressure during exercise stress echocardiography may provide additional
      prognostic information beyond resting evaluation. Cardiac magnetic resonance is
      also useful for assessing right ventricular geometry and function, which provide
      additional prognostic information in patients with VHD and PH. 

PMID- 25592698
TI  - Association of myocardial T1-mapping CMR with hemodynamics and RV performance in
      pulmonary hypertension.
AB  - Early detection of right ventricular (RV) involvement in chronic pulmonary
      hypertension (PH) is essential due to prognostic implications. T1 mapping by
      cardiac magnetic resonance (CMR) has emerged as a noninvasive technique for
      extracellular volume fraction (ECV) quantification. We assessed the association
      of myocardial native T1 time and equilibrium contrast ECV (Eq-ECV) at the RV
      insertion points with pulmonary hemodynamics and RV performance in an
      experimental model of chronic PH. Right heart catheterization followed by
      immediate CMR was performed on 38 pigs with chronic PH (generated by surgical
      pulmonary vein banding) and 6 sham-operated controls. Native T1 and Eq-ECV values
      at the RV insertion points were both significantly higher in banded animals than
      in controls and showed significant correlation with pulmonary hemodynamics, RV
      arterial coupling, and RV performance. Eq-ECV values also increased before overt
      RV systolic dysfunction, offering potential for the early detection of myocardial
      involvement in chronic PH. 

PMID- 25592700
TI  - MDCT assessment of mechanical circulatory support device complications.

PMID- 25592701
TI  - Diagnostic value of quantitative CMR in patients suspected of having myocarditis:
      a question of timing.

PMID- 25592702
TI  - Reply: Diagnostic value of quantitative CMR in patients suspected of having
      myocarditis: a question of timing.

PMID- 25592703
TI  - Discordance between ischemia and stenosis, or PINSS and NIPSS: are we ready for
      new vocabulary?

PMID- 25592705
TI  - Imaging at the 2014 ACC Legislative Conference: a debrief.

PMID- 25592704
TI  - Is it T1me for tissue characterization in myocarditis?

PMID- 25592706
TI  - Skeletal stability following mandibular advancement with and without advancement
      genioplasty.
AB  - The correction of most cases of skeletal class II mandibular deficiency requires
      surgical advancement of the mandible for treatment of the malocclusion. Often
      genioplasty is included in the procedure to improve the soft tissue profile. Long
      term skeletal stability is an important goal for the surgeon and orthodontist
      following bilateral sagittal split osteotomy (BSSO) and is influenced by the
      muscles attached to the mandible. Following the surgical advancement of the
      mandible, the suprahyoid muscle complex is stretched and even more so when the
      procedure is combined with surgical advancement of the chin. This retrospective
      comparative study determined the long-term skeletal stability of patients who had
      undergone surgical advancement of the mandible by means of BSSO with an
      advancement genioplasty, compared to those who had undergone mandibular
      advancement surgery (BSSO) without an advancement genioplasty. This study
      concluded that the postoperative hard tissue relapse following BSSO advancement,
      with or without genioplasty, was clinically insignificant. 

PMID- 25592707
TI  - Synthesis and in vitro characterization of cinnoline and benzimidazole analogues
      as phosphodiesterase 10A inhibitors.
AB  - Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A)
      inhibitors were synthesized as potential PET radiopharmaceuticals and their in
      vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one
      compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to
      18.6nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52+/-0.18,
      2.86+/-0.10, and 3.73+/-0.60nM, respectively; these three compounds also showed
      high in vitro selectivity (>1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The
      high potency and selectivity of these three compounds suggests that they could be
      radiolabeled with PET radionuclides for further evaluation of their in vivo
      pharmacological behavior and ability to quantify PDE10A in the brain. 

PMID- 25592708
TI  - Inhibitory constituents of Sophora tonkinensis on nitric oxide production in RAW
      264.7 macrophages.
AB  - Bioactivity-guided fractionation of the MeOH extract from the roots of Sophora
      tonkinensis resulted in the isolation of a new pterocarpan glycoside (1) together
      with nine known compounds, maackiain (2), sophoranone (3), sophoranochromene (4),
      pinoresinol (5), syringaresinol (6), medioresinol (7), 4',7-dihydroxyflavone (8),
      calycosin (9), and genistein (10). The structure of the new compound was
      determined on the basis of spectroscopic analysis including NMR and CD data in
      combination with acid hydrolysis. Compounds 1-4 exhibited the inhibitory effects
      on LPS-induced nitric oxide production with IC50 values ranging from 13.6 to
      33.0MUM in RAW 264.7 macrophages. 

PMID- 25592709
TI  - Novel synthetic coumarins that targets NF-kappaB in Hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor
      worldwide, and is the third most common cause of cancer related death.
      Constitutive activation of NF-kappaB is the underlying mechanism behind
      tumorigenesis and this protein regulates the expression of genes involved in
      proliferation, survival, drug resistance, angiogenesis and metastasis. The design
      of inhibitors which suppress NF-kappaB activation is therefore of great
      therapeutic importance in the treatment of HCC. In this study, we investigated
      the effect of newly synthesized coumarin derivatives against HCC cells, and
      identified (7-Carbethoxyamino-2-oxo-2H-chromen-4-yl)methylpyrrolidine-1
      carbodithioate (CPP) as lead compound. Further, we evaluated the effect of CPP on
      the DNA binding ability of NF-kappaB, CXCL12-induced cell migration and invasion,
      and the regulated gene products in HCC cells. We found that CPP induced
      cytotoxicity in three HCC cells in a time and dose dependent manner, and
      suppressed the DNA binding ability of NF-kappaB. CPP significantly decreased the
      CXCL12-induced cell migration and invasion. More evidently, CPP inhibits the
      expression of NF-kappaB targeted genes such as cyclin D1, Bcl-2, survivin, MMP12
      and C-Myc. Furthermore, the molecular docking analysis suggested that CPP
      interacts with the p50 binding domain of the p65 subunit, scoring best among the
      26 docked coumarin derivatives of this study. Thus, we are reporting CPP as a
      potent inhibitor of the pro-inflammatory pathway in Hepatocellular carcinoma. 

PMID- 25592710
TI  - Prodrugs of imidazotriazine and pyrrolotriazine C-nucleosides can increase anti
      HCV activity and enhance nucleotide triphosphate concentrations in vitro.
AB  - A number of prodrugs of HCV-active purine nucleoside analogues 2'-C-methyl 4-aza
      9-deaza adenosine 1, 2'-C-methyl 4-aza-7,9-dideaza adenosine 2, 2'-C-methyl 4-aza
      9-deaza guanosine 3 and 2'-C-methyl 4-aza-7,9-dideaza guanosine 4 were prepared
      and evaluated to improve potency, selectivity and liver targeting.
      Phosphoramidate guanosine prodrugs (3a-3k and 4a, b) showed insufficient cell
      activity for further profiling. Striking enhancement in replicon activity
      relative to the parent was observed for phosphoramidate imidazo[2,1
      f][1,2,4]triazine-4-amine adenosine prodrugs (1a-1p), but this was accompanied by
      an increase in cytotoxicity. Improved or similar potency without a concomitant
      increase in toxicity relative to the parent was demonstrated for phosphoramidate
      pyrrolo[2,1-f][1,2,4]triazine-4-amine adenosine prodrugs (2a-2k). Carbamate,
      ester and mixed prodrugs of 2 showed mixed results. Selected prodrugs of 2 were
      analysed for activation to the triphosphate, with most demonstrating much better
      activation in hepatocytes over replicon cells. The best activation was observed
      for a mixed phosphoramidate-3'ester (11) followed by a simple 3'-ester (10). 

PMID- 25592711
TI  - Synthesis, antimicrobial activity and molecular docking of novel tetracyclic
      scaffolds incorporating a flavonoid framework with medium sized oxygen
      heterocycles.
AB  - A convenient approach for the synthesis of novel tetracyclic scaffolds
      incorporating a flavonoid framework with medium sized heterocyclic rings (eight-,
      nine-, ten- and eleven-membered rings) containing two oxygen atoms from flavonols
      through alkylation using different dibromoalkanes was described. The synthesized
      compounds were established based on the spectral data and X-ray crystal structure
      for 6c. The synthesized compounds were evaluated for their in vitro antimicrobial
      activity. Docking studies were carried out for most active two compounds 6f and
      6i. 

PMID- 25592713
TI  - Pyridine and pyridinone-based factor XIa inhibitors.
AB  - The structure-activity relationships (SAR) of six-membered ring replacements for
      the imidazole ring scaffold is described. This work led to the discovery of the
      potent and selective pyridine (S)-23 and pyridinone (+/-)-24 factor XIa
      inhibitors. SAR and X-ray crystal structure data highlight the key differences
      between imidazole and six-membered ring analogs. 

PMID- 25592712
TI  - Dithiocarbamate-thiourea hybrids useful as vaginal microbicides also show reverse
      transcriptase inhibition: design, synthesis, docking and pharmacokinetic studies.
AB  - Prophylactic prevention is considered as the most promising strategy to tackle
      STI/HIV. Twenty-five dithiocarbamate-thiourea hybrids (14-38) were synthesized as
      woman controlled topical vaginal microbicides to counter Trichomonas vaginalis
      and sperm along with RT inhibition potential. The four promising compounds (18,
      26, 28 and 33) were tested for safety through cytotoxic assay against human
      cervical cell line (HeLa) and compatibility with vaginal flora, Lactobacillus.
      Docking study of most promising vaginal microbicide (33) revealed that it docked
      in a position and orientation similar to known reverse transcriptase inhibitor
      Nevirapine. The preliminary in vivo pharmacokinetics of compound 33 was performed
      in NZ-rabbits to evaluate systemic toxicity in comparison to Nonoxynol-9. 

PMID- 25592714
TI  - Biofilm inhibition of linezolid-like Schiff bases: synthesis, biological
      activity, molecular docking and in silico ADME prediction.
AB  - Herein, we report the synthesis and screening of linezolid-like Schiff bases as
      inhibitors of biofilm formation. The result of biofilm inhibition of Pseudomonas
      aeruginosa suggested that compounds 5h (IC50 value=12.97+/-0.33MUM) and 5i (IC50
      value=15.63+/-0.20MUM) had more inhibitory activity when compared with standard
      linezolid (IC50=15.93+/-0.18MUM) without affecting the growth of cells (and thus
      behave as anti-quorum sensing agents). The compounds 5h (MIC range=2.5-10MUg/mL)
      and 5i (MIC range=3.5-10MUg/mL) with 2-chloroquinolinyl and 2-chloro-8
      methylquinolinyl motif, respectively, showed antibacterial activity in comparable
      range of linezolid (MIC range=2-3MUg/mL) and were more potent when compared with
      ciprofloxacin (MIC range=25-50MUg/mL). Thus, the active derivatives were not only
      potent inhibitors of P. aeruginosa biofilm growth but also efficient
      antibacterial agents. The docking study of most active compounds 5h and 5i
      against PqsD enzyme of P. aeruginosa exhibited good binding properties. In silico
      ADME properties of synthesized compounds were also analyzed and showed potential
      to develop as good oral drug candidates. 

PMID- 25592715
TI  - Synthesis and membrane-protective activity of novel derivatives of alpha
      mangostin at the C-4 position.
AB  - A series of new C-4-derivatives of alpha-mangostin has been synthesized with the
      use of Mannich reaction and alkylation with 4-bromomethyl-2,6-dialkylphenols. It
      has been shown on a model of H2O2-induced erythrocyte hemolysis that the Mannich
      bases containing morpholinomethyl and piperidinomethyl fragments differ from
      parent alpha-mangostin by their high antioxidant and membrane-protective
      activity. 

PMID- 25592716
TI  - Insights on the role of boron containing moieties in the design of new potent and
      efficient agonists targeting the beta2 adrenoceptor.
AB  - The development of beta2 adrenoceptor (beta2AR) agonists is of increasing
      interest because of their wide-ranging applications in medicine, particularly for
      the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle
      that lines airways of mammals, some boron-containing adducts have demonstrated
      greater potency and efficacy compared to well-known boron-free compounds. We
      herein report the design and synthesis as well as the chemical and
      pharmacological characterization of a new boron-containing compound: ((R)-6-((S)
      2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2]
      dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound
      induced relaxation of smooth muscle in guinea pig tracheal rings with greater
      potency and efficacy (EC50?28.02nM). Theoretical studies suggest the potential
      selectivity of this boron containing compound on the orthosteric site of beta
      adrenoceptors and/or signaling pathways, as well as the importance of the
      tetracoordinated boron atom in its structure for binding recognition properties. 

PMID- 25592717
TI  - Increased plasma DPP4 activities predict new-onset hyperglycemia in Chinese over
      a four-year period: possible associations with inflammation.
AB  - OBJECTIVE: DPP4, a novel proinflammatory cytokine, is involved in the
      inflammatory process through its interaction with the IGF-II/M6P receptor. Our
      objective was to determine whether DPP4 acts as a link between low-grade chronic
      inflammation and hyperglycemia. DESIGN AND METHODS: A prospective cohort study
      was conducted with 486 adults (177 men and 309 women) aged 18 to 70years without
      hyperglycemia examined in 2007 (baseline) and 2011 (follow-up). Circulating DPP4
      activity, IGF-II/M6P receptor, and inflammatory markers were measured at baseline
      and four years later. RESULTS: After a four-year follow-up period, 111
      individuals developed hyperglycemia (71 prediabetes and 40 type 2 diabetes).
      According to the multiple linear regression analysis, the baseline DPP4 activity
      was an independent predictor of an increase in the IGF-II/M6P receptor,
      inflammatory markers, and insulin resistance over the four-year period (all P
      <0.05). In the multivariable-adjusted models, the odds ratio (OR) for incident
      hyperglycemia comparing the highest and lowest quartiles of DPP4 activity was
      2.90 (95% CI 1.47-5.73) after adjustment for confounding risk factors (P=0.002).
      The incidence of hyperglycemia because of DPP4 activity increased by 9.47%.
      Furthermore, the plasma DPP4 activity significantly improved the area under the
      ROC curve for predicting new-onset hyperglycemia based on the information from
      the baseline levels of the risk factors (P=0.036). CONCLUSIONS: DPP4 activity is
      an important predictor of the onset of insulin resistance and hyperglycemia in
      apparently healthy Chinese. This finding may have important implications for
      understanding the proinflammatory role of DPP-4 in the development and
      pathogenesis of hyperglycemia.

PMID- 25592719
TI  - Chronic hepatitis C infection as a risk factor for renal cell carcinoma.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection causes cirrhosis and
      hepatocellular carcinoma but is also etiologically linked to several extrahepatic
      medical conditions including renal disorders. HCV is also associated with
      extrahepatic malignancies and may be oncogenic. Whether HCV confers an increased
      risk of renal cell carcinoma (RCC) remains controversial. AIMS: Prospectively
      determine whether chronic HCV is associated with an increased risk of RCC.
      METHODS: At an integrated medical center in Detroit, Michigan, adult patients
      with suspected RCC or newly diagnosed colon cancer (controls) were screened for
      hepatitis C antibody (HCAB) and HCV RNA. Renal or colon cancers were confirmed
      histologically. The proportion of patients with HCAB and HCV RNA in each group
      was compared, and risk factors for renal cell carcinoma were determined by
      multivariable logistic regression analysis. RESULTS: RCC patients had a higher
      rate of HCAB positivity (11/140, 8 %) than colon cancer patients (1/100, 1 %) (p
      < 0.01). Of the HCAB-positive patients, 9/11 RCC and 0/1 controls had detectable
      HCV RNA. HCV RNA positivity was a significant risk factor for RCC (OR 24.20; 95 %
      CL 2.4, >999.9; p = 0.043). Additionally, viremic RCC patients were significantly
      younger than RCC patients who were HCV RNA negative (p = 0.013). CONCLUSIONS:
      Patients with chronic HCV are at heightened risk of RCC.

PMID- 25592718
TI  - c-Fos Protects Neurons Through a Noncanonical Mechanism Involving HDAC3
      Interaction: Identification of a 21-Amino Acid Fragment with Neuroprotective
      Activity.
AB  - Proteins belonging to the AP-1 family of transcription factors are known to be
      involved in the regulation of neuronal viability. While strides have been made to
      elucidate the mechanisms of how individual members regulate cell death, much
      remains unknown. We find that the expression of one AP-1 member, c-Fos, is
      reduced in cerebellar granule neurons (CGNs) induced to die by low potassium (LK)
      treatment. Restoration and increase of this expression protect CGNs against LK
      induced death, whereas knockdown induces death of otherwise healthy neurons.
      Furthermore, forced expression can protect cortical neurons against homocysteic
      acid (HCA)-induced toxicity. Taken together, this suggests that c-Fos is
      necessary for neuronal survival and that elevating c-Fos expression has a
      neuroprotective effect. Consistent with this idea is the finding that c-Fos
      expression is reduced selectively in the striatum in two separate mouse models of
      Huntington's disease and forced expression protects against neuronal death
      resulting from mutant huntingtin (mut-Htt) expression. Interestingly,
      neuroprotection by c-Fos does not require its DNA-binding, transcriptional, or
      heteromerization domains. However, this protective activity can be inhibited by
      pharmacological inhibition of c-Abl, CK-I, and MEK-ERK signaling. Additionally,
      expression of point mutant forms of this protein has identified that mutation of
      a tyrosine residue, Tyr345, can convert c-Fos from neuroprotective to neurotoxic.
      We show that c-Fos interacts with histone deacetylase-3 (HDAC3), a protein that
      contributes to mut-Htt neurotoxicity and whose overexpression is sufficient to
      promote neuronal death. When co-expressed, c-Fos can protect against HDAC3
      neurotoxicity. Finally, our study identifies a 21-amino acid region at the C
      terminus of c-Fos that is sufficient to protect neurons against death induced by
      LK, HCA treatment, or mut-Htt expression when expressed via a plasmid
      transfection or as a cell-permeable peptide. This cell-permeable peptide,
      designated as Fos-CTF, could have potential as a therapeutic agent for
      neurodegenerative diseases. 

PMID- 25592721
TI  - Galiellalactone analogs and their possible precursors from Sarcosomataceae.
AB  - Galiellalactone analogs (1-4) (including two new compounds), together with their
      possible precursors (5-9, named pregaliellalactone B-F), were obtained from the
      solid cultures of an endophytic fungus Sarcosomataceae NO.45-1-8-1. Their
      chemical structures were elucidated by analyses of HR ESI-TOF MS, 1D-, 2D-NMR, CD
      spectra and single crystal X-ray diffraction methods. Compounds 5-9, the possible
      precursors of galiellalactone analogs, were found to exist as enantiomers for the
      first time. The cytotoxicity of these compounds against six tumor cell lines was
      examined and preliminary structure-activity relationship (SAR) was also
      discussed. 

PMID- 25592722
TI  - An elderly patient with recurrent episodes of hemi-paresthesia. Cerebral amyloid
      angiopathy (CAA).

PMID- 25592720
TI  - Public perceptions about risk and protective factors for cognitive health and
      impairment: a review of the literature.
AB  - BACKGROUND: Preventing and/or delaying cognitive impairment is a public health
      priority. To increase awareness of and participation in behaviors that may help
      maintain cognitive function or reduce risk of impairment, we need to understand
      public perceptions about risk and protective factors. METHODS: We conducted a
      scoping review of studies examining the public's perceptions about risk and
      protective factors related to cognitive health and impairment published since the
      2007 National Public Health Road Map to Maintaining Cognitive Health. RESULTS: A
      search of five databases yielded 1,115 documents published between June 2007 and
      December 2013. Initial review of abstracts identified 90 potentially eligible
      studies. After full-article review, 30 met inclusion criteria; four additional
      articles identified in reference lists also met inclusion criteria. Of the 34, 16
      studies addressed Alzheimer's disease (AD) specifically, 15 dementia broadly, 5
      mild to moderate cognitive impairment, and 8 normal functioning, with some
      content overlap. Across studies, respondents reported genetics (n = 14 studies),
      older age (n = 8), stress (n = 7), brain/head injury (n = 6), and mental
      illness/brain disease (n = 6) as perceived risk factors for AD and dementia.
      Protective factors most commonly identified for maintaining cognitive health were
      intellectual/mental stimulation (n = 13), physical activity (n = 12), healthy
      diet (n = 10), and social/leisure activities (n = 10). CONCLUSIONS: Studies
      identified genetics and older age as key perceived risk factors more so than
      behaviors such as smoking. Individuals perceived that numerous lifestyle factors
      (e.g. intellectual stimulation, physical activity) could protect against
      cognitive impairment, AD, and/or dementia. Results can inform national and
      international education efforts about AD and other dementias.

PMID- 25592723
TI  - Genotyping of CCR5 gene, CCR2b and SDF1 variants related to HIV-1 infection in
      Gabonese subjects.
AB  - OBJECTIVE: Given the magnitude of the HIV epidemic infection, many viral and
      human factors were analyzed, and the most decisive was the variant CCR5-Delta32.
      The presence of a low HIV prevalence (1.8%) in Gabon in the 1990s, compared to
      neighboring countries, represents a paradox that led us to search for viral and
      human genetic variants in this country. In this study, only variants of
      coreceptors and chemokines were investigated. METHODS: Variants of the coding
      region of the CCR5 gene were analyzed by denaturing gradient gel electrophoresis,
      and then variants of SDF1 and CCR2b were determined by polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: Four rare variants of the CCR5
      coreceptor were found, while CCR5-Delta32 and CCR5m303 variants were not found.
      No association with CCR2b-V64I (17%) and SDF1-3'A (2%) variants was determined in
      relation to HIV-1 infection in Gabonese patients. CONCLUSION: The paradox of HIV
      seroprevalence in Gabon, which ended in the 2000s, was not caused by human
      genetic variants but rather by environmental factors.

PMID- 25592724
TI  - Lentiviral-mediated overexpression of homeobox A4 by human umbilical cord
      mesenchymal stem cells repairs full-thickness skin defects.
AB  - A number of types of stem cells have been shown to be effective in wound repair.
      In the present study the effect of homeobox A4 (HOXA4) overexpression by human
      umbilical cord mesenchymal stem cells (hUMSCs) on full-thickness skin repair was
      evaluated. Isolated hUMSCs were transfected with a lentivirus expressing HOXA4
      and cultured for 21 days. Expression of the epidermal cell-specific markers,
      cytokeratins 14 and 18, was detected by immunohistochemistry and flow cytometry.
      Full-thickness skin defects (1.5 cm x 1.5 cm) were made on the backs of 45 nude
      mice, which were randomly divided into the following three treatment groups:
      Collagen membrane with lenti-HOXA4 hUMSC seed cells; collagen membrane with
      lentivirus expressing green fluorescent protein; and collagen membrane alone. On
      days 7, 14 and 21 following transplantation, tissue samples were harvested and
      examined by histology and western blot analysis. Flow cytometry showed that the
      transfection efficiency was 95.41% at a multiplicity of infection of 100, and
      that the lenti-HOXA4 hUMSCs differentiated into epidermal cells, expressing
      cytokeratins 14 and 18. In addition, re-epithelialization of wounds treated with
      lenti-HOXA4 hUMSCs was significantly greater than that in the control groups in
      the first week. By week three the epidermis was significantly thicker in the
      lenti-HOXA4 group than the control groups. Thus, transplantation of hUMSCs
      modified with Ad-HOXA4 promoted wound healing.

PMID- 25592725
TI  - Surveillance of prosthetic joint infections: international overview and new
      insights for hospital databases.
AB  - Since the US National Nosocomial Infections Surveillance System was implemented
      in the 1970s, several countries have developed their own surveillance systems,
      all including surgical site infection (SSI) as a major target. However, the
      performance of such systems needs to be evaluated further in terms of data
      quality and cost-effectiveness. The current article presents a literature
      overview of the main strategies used for SSI surveillance worldwide, focusing on
      hip and knee arthroplasty infections, and discusses new issues for further
      development of surveillance databases. 

PMID- 25592726
TI  - Preventing invasive candida infections. Where could we do better?
AB  - Invasive candidiasis is associated with high mortality rates, ranging from 35% to
      60%, in the range reported for septic shock. The epidemiology and pathogenesis of
      invasive candidiasis differ according to the patient's immune status; the
      majority of cases in immunocompromised hosts are candidaemia, whereas non
      candidaemic systemic candidiasis accounts for the majority of cases in critically
      ill patients. In contrast to candidaemia, non-candidaemic systemic candidiasis is
      difficult to prove, especially in critically ill patients. Up to 80% of these
      patients are colonized, but only 5-30% develop invasive infection. The
      differentiation of colonization and proven infection is challenging, and
      evolution from the former to the latter requires seven to 10 days. This continuum
      from colonization of mucosal surfaces to local invasion and then invasive
      infection makes it difficult to identify those critically ill patients likely to
      benefit most from antifungal prophylaxis or early empirical antifungal treatment.
      Early empirical treatment of non-candidaemic systemic candidiasis currently
      relies on the positive predictive value of risk assessment strategies, such as
      the colonization index, candida score, and predictive rules based on combinations
      of risk factors such as candida colonization, broad-spectrum antibiotics, and
      abdominal surgery. Although guidelines recently scored these strategies as being
      supported by limited evidence, they are widely used at bedside and have
      substantially decreased the incidence of invasive candidiasis. 

PMID- 25592727
TI  - Is There a Role for DAT-SPECT Imaging in a Specialty Movement Disorders Practice?
AB  - OBJECTIVE: Analyze indications for ordering DAT-SPECT scans and the clinical
      impact of scan results on patients evaluated in a movement disorders practice.
      BACKGROUND: DAT-SPECT is FDA approved to evaluate cases of suspected presynaptic
      dopaminergic deficiency. Little data is available on clinical use and impact of
      these scans among movement disorders neurologists. METHODS: DAT-SPECT scans
      ordered at the Northwestern University Parkinson's disease (PD) and movement
      disorders center from 2011-2013 were reviewed. Clinic notes were reviewed for
      information regarding the indication for ordering each scan, and to assess for
      any changes in clinical impression or management choices that followed the scan.
      RESULTS: 83 scans were ordered by four specialists. Scans were commonly ordered
      to differentiate PD from Essential Tremor (21.7%, n = 18) or from drug-induced
      parkinsonism (21.7%, n = 18). In 59% (n = 49) of cases, a change in clinical
      diagnosis or medication regimen occurred within one visit after the scan. The
      strongest impact was seen for the indication of ET vs. PD in which 72.2% (n = 13)
      had a change in diagnosis, management, or both. CONCLUSIONS: Diagnostic
      uncertainty in cases of parkinsonism exists even in a tertiary referral center.
      DAT-SPECT has significant impact on clinical diagnosis and management even in the
      hands of movement disorders specialists.

PMID- 25592728
TI  - Novel monoclonal antibody against truncated C terminal region of Histidine Rich
      Protein2 (PfHRP2) and its utility for the specific diagnosis of malaria caused by
      Plasmodium falciparum.
AB  - An accurate diagnosis of malarial infection is an important element in combating
      this deadly disease. Malaria diagnostic test including, microscopy and other
      molecular tests are highly sensitive but too complex for field conditions. Rapid
      detection tests for P. falciparum infection using monoclonal antibodies (mAbs)
      against highly polymorphic PfHRP2 (Histidine Rich Protein2) are still most
      preferred test in field conditions, but with limitations such as specificity, and
      sensitivity leading to false positive and false negative results. To overcome
      these limitations, we carried out bioinformatics analysis PfHRP2 and PfHRP3 and
      found that the C-terminal region of PfHRP2 (~105 amino acids) displayed
      relatively lower sequence identity with PfHRP3. This C-terminal region of PfHRP2
      contained unique peptide repeats and was found to be conserved in various
      isolates of P. falciparum. Moreover, this region was also found to be highly
      antigenic as predicted by antigenicity propensity scores. Thus we constructed a
      cDNA clone of the truncated PfHRP2 (recPfHRP2-T3) coding for C-terminal 105 amino
      acids and expressed it in E. coli and purified the polypeptide to homogeneity.
      The purified recPfHRP2-T3 was used as an antigen for development of both
      polyclonal and monoclonal antibody (mAb). The mAbs b10c1 and Aa3c10 developed
      against recPfHRP2-T3 was found to efficiently recognize recombinant PfHRP2 but
      not PfHRP3. In addition, the above mAbs reacted positively with spent media and
      serum sample of P. falciparum infection recognizing the native PfHRP2. The
      affinity constant of both the clones were found to be 10(9) M(-1).
      Quantitatively, both these clones showed ~4.4 fold higher reactivity with P.
      falciparum infected serum compared to serum from healthy volunteers or P. vivax
      infected patient samples. Thus these anti-C-terminal PfHRP2 mAbs (Aa3c10 and
      b10c1) display a very high potential for improvising the existing malarial
      diagnostic tools for detection of P. falciparum infection especially in areas
      where PfHRP2 polymorphism is highly prevalent. 

PMID- 25592729
TI  - Development and application of three-dimensional skin equivalents for the
      investigation of percutaneous worm invasion.
AB  - Investigation of percutaneous helminth infection is generally based on animal
      models or excised skin. As desirable replacement of animal experiments, tissue
      engineered skin equivalents have recently been applied in microbial and viral in
      vitro infection models. In the present study, the applicability of tissue
      engineered skin equivalents for the investigation of percutaneous helminth
      invasion was evaluated. Epidermal and a full-thickness skin equivalents that suit
      the requirements for helminth invasion studies were developed. Quantitative
      invasion assays were performed with the skin-invading larvae of the helminths
      Strongyloides ratti and Schistosoma mansoni. Both skin equivalents provided a
      physical barrier to larval invasion of the nematode S. ratti, while these larvae
      could invade and permeate a cell-free collagen scaffold and ex vivo epidermis. In
      contrast, the epidermal and full-thickness skin equivalents exhibited a human
      host-specific susceptibility to larvae of trematode S. mansoni, which could well
      penetrate. Invasion of S. mansoni in cell-free collagen scaffold was lowest for
      all experimental conditions. Thus, reconstructed epidermis and full-thickness
      skin equivalents confirmed a high degree of accordance to native tissue.
      Additionally, not only tailless schistosomula but also cercariae could permeate
      the skin equivalents, and thus, delayed tail loss hypothesis was supported. The
      present study indicates that the limitations in predictive infection test systems
      for human-pathogenic invading helminths can be overcome by tissue-engineered in
      vitro skin equivalents allowing a substitution of the human skin for analysis of
      the interaction between parasites and their hosts' tissues. This novel tissue
      engineered technology accomplishes the endeavor to save animal lives. 

PMID- 25592730
TI  - Toxoplasma gondii: cloning, expression and immunoreactivity of recombinant ROP5
      and ROP18 antigens.
AB  - Early diagnosis and determining the infective stage are critical for effective
      therapy of toxoplasmosis. Owing to the progress in biotechnology, commonly used
      native, non-standardized diagnostic antigens should be replaced by genetically
      engineered antigens. The recombinant proteins are also promising components of
      subunit vaccines against Toxoplasma gondii infections. A strategic biological
      role of rhoptry proteins (ROP) in parasitophorous vacuole biogenesis and
      virulence of the parasite creates a necessity for an intensive study on the
      serological activity and immunogenicity of newly developed recombinant ROP
      antigens. Our findings indicate that all generated preparations of recombinant
      ROP5 and ROP18 antigens, expressed in Escherichia coli bacteria, are recognized
      by specific antibodies produced during acute and chronic infections in inbred
      laboratory mice. We noticed, for the first time, that ROP5 IgM antibodies are an
      early and sensitive marker of T. gondii infection. The proven immunoreactivity of
      the obtained preparations has become a premise for a further study on their
      utility in routine diagnosis of human and animal toxoplasmosis as well as in the
      immunoprevention of T. gondii infection (as the main or supplementary component
      of the vaccine). 

PMID- 25592731
TI  - Fatty acid metabolism in the regulation of T cell function.
AB  - The specific regulation of cellular metabolic processes is of major importance
      for directing immune cell differentiation and function. We review recent evidence
      indicating that changes in basic cellular lipid metabolism have critical effects
      on T cell proliferation and cell fate decisions. While induction of de novo fatty
      acid (FA) synthesis is essential for activation-induced proliferation and
      differentiation of effector T cells, FA catabolism via beta-oxidation is
      important for the development of CD8(+) T cell memory as well as for the
      differentiation of CD4(+) regulatory T cells. We consider the influence of lipid
      metabolism and metabolic intermediates on the regulation of signaling and
      transcriptional pathways via post-translational modifications, and discuss how an
      improved understanding of FA metabolism may reveal strategies for manipulating
      immune responses towards therapeutic outcomes. 

PMID- 25592732
TI  - Security and cost comparison of INR self-testing and conventional hospital INR
      testing in patients with mechanical heart valve replacement.
AB  - BACKGROUND: International normalized ratio (INR) self-testing can improve the
      management of anticoagulation therapy with warfarin for the patients following
      mechanical heart valve replacement. Several reviews and studies have demonstrated
      self-management as an option to improve patient's outcome considerably after
      mechanical heart valve replacement. We sought to analyze the security, economy
      and discuss the prospect of self-testing of anticoagulation therapy in patients
      following mechanical heart valve replacement in China, and evaluate the accuracy
      and stability of CoaguChek XS portable INR-testing device. METHODS: This was a
      prospective self-controlled clinical study conducted with 526 patients receiving
      oral warfarin anticoagulation therapy after mechanical heart valve replacement in
      the period of Mar.1, 2012 - Nov.1, 2012 in Cardiovascular Surgery Department of
      West China Hospital of Sichuan University. The same patient performed INR testing
      with CoaguChek XS portable coagulometer (group1) and central lab (group 2) in
      parallel. The follow-up time was 6 months. Meanwhile, a questionnaire was handed
      out to survey the expenses required for the re-examination visits to the
      hospital, time, and anticoagulation complications. RESULTS: No severe
      anticoagulation complications occurred in all the patients. No significant
      difference of the INR results were observed between group 1 and group 2, they
      showed significant relevance, r = 0.953(p < 0.05). Compared with the conventional
      method of INR testing in hospital, the portable coagulometer is convenient, quick
      and less traumatic. Self-testing of anticoagulation therapy reduced the cost and
      the time required for re-examination. CONCLUSIONS: Results of CoaguChek XS
      monitor are precise and have a good consistency and stability as compared with
      traditional laboratory testing. For the patients receiving anticoagulation
      therapy after mechanical heart valve replacement, the self-testing of
      anticoagulation therapy with portable coagulometer is a safe choice, and it has a
      promising future application in China.

PMID- 25592733
TI  - Enrichment of aliphatic, alicyclic and aromatic acids by oil-degrading bacteria
      isolated from the rhizosphere of plants growing in oil-contaminated soil from
      Kazakhstan.
AB  - Three microbial strains were isolated from the rhizosphere of alfalfa (Medicago
      sativa), grass mixture (Festuca rubra, 75 %; Lolium perenne, 20 %; Poa pratensis,
      10 %), and rape (Brassica napus) on the basis of their high capacity to use crude
      oil as the sole carbon and energy source. These isolates used an unusually wide
      spectrum of hydrocarbons as substrates (more than 80), including n-alkanes with
      chain lengths ranging from C12 to C32, monomethyl- and monoethyl-substituted
      alkanes (C12-C23), n-alkylcyclo alkanes with alkyl chain lengths from 4 to 18
      carbon atoms, as well as substituted monoaromatic and diaromatic hydrocarbons.
      These three strains were identified as Gordonia rubripertincta and Rhodococcus
      sp. SBUG 1968. During their transformation of this wide range of hydrocarbon
      substrates, a very large number of aliphatic, alicyclic, and aromatic acids was
      detected, 44 of them were identified by GC/MS analyses, and 4 of them are
      described as metabolites for the first time. Inoculation of plant seeds with
      these highly potent bacteria had a beneficial effect on shoot and root
      development of plants which were grown on oil-contaminated sand.

PMID- 25592735
TI  - Transcriptome analysis of rainbow trout in response to non-virion (NV) protein of
      viral haemorrhagic septicaemia virus (VHSV).
AB  - The non-virion (NV) protein of viral haemorrhagic septicaemia virus (VHSV), an
      economically important fish novirhabdovirus, has been implicated in the
      interference of some host innate mechanisms (i.e. apoptosis) in vitro. This work
      aimed to characterise the immune-related transcriptome changes in rainbow trout
      induced by NV protein that have not yet been established in vivo. For that
      purpose, immune-targeted microarrays were used to analyse the transcriptomes from
      head kidney and spleen of rainbow trout (Oncorhynchus mykiss) after injection of
      recombinant NV (rNV). Results showed the extensive downregulation (and in some
      cases upregulation) of many innate and adaptive immune response genes not related
      previously to VHSV infection. The newly identified genes belonged to VHSV-induced
      genes (vigs), tumour necrosis factors, Toll-like receptors, antigen processing
      and presentation, immune co-stimulatory molecules, interleukins, macrophage
      chemotaxis, transcription factors, etc. Classification of differentially
      downregulated genes into rainbow trout immune pathways identified stat1 and
      jun/atf1 transcription factor genes as the most representative of the multipath
      gene targets of rNV. Altogether, these results contribute to define the role and
      effects of NV in trout by orchestrating an immunosuppression of the innate immune
      responses for favouring viral replication upon VHSV infection. Finally, these
      transcriptome results open up the possibility to find out new strategies against
      VHSV and better understand the interrelationships between some immune pathways in
      trout. 

PMID- 25592734
TI  - Spatio-temporal variability of airborne bacterial communities and their
      correlation with particulate matter chemical composition across two urban areas.
AB  - The study of spatio-temporal variability of airborne bacterial communities has
      recently gained importance due to the evidence that airborne bacteria are
      involved in atmospheric processes and can affect human health. In this work, we
      described the structure of airborne microbial communities in two urban areas
      (Milan and Venice, Northern Italy) through the sequencing, by the Illumina
      platform, of libraries containing the V5-V6 hypervariable regions of the 16S rRNA
      gene and estimated the abundance of airborne bacteria with quantitative PCR
      (qPCR). Airborne microbial communities were dominated by few taxa, particularly
      Burkholderiales and Actinomycetales, more abundant in colder seasons, and
      Chloroplasts, more abundant in warmer seasons. By partitioning the variation in
      bacterial community structure, we could assess that environmental and
      meteorological conditions, including variability between cities and seasons, were
      the major determinants of the observed variation in bacterial community
      structure, while chemical composition of atmospheric particulate matter (PM) had
      a minor contribution. Particularly, Ba, SO4 (2-) and Mg(2+) concentrations were
      significantly correlated with microbial community structure, but it was not
      possible to assess whether they simply co-varied with seasonal shifts of
      bacterial inputs to the atmosphere, or their variation favoured specific taxa.
      Both local sources of bacteria and atmospheric dispersal were involved in the
      assembling of airborne microbial communities, as suggested, to the one side by
      the large abundance of bacteria typical of lagoon environments (Rhodobacterales)
      observed in spring air samples from Venice and to the other by the significant
      effect of wind speed in shaping airborne bacterial communities at all sites. 

PMID- 25592736
TI  - Copper homeostasis-related genes in three separate transcriptional units
      regulated by CsoR in Corynebacterium glutamicum.
AB  - In Corynebacterium glutamicum R, CsoR acts as a transcriptional repressor not
      only of the cognate copA-csoR operon but also of the copZ1-copB-cgR_0126 operon.
      It is predicted that copA and copB encode P-type ATPases for copper efflux and
      copZ1 encodes a metallochaperone. Here, a CsoR-binding motif was found upstream
      of another copZ-like gene, copZ2, and the in vitro binding of the CsoR protein to
      its promoter was confirmed. The monocistronic copZ2 transcript was upregulated by
      excess copper in a CsoR-dependent manner. Among the extended CsoR regulon,
      deletion of copA, but not of copB, copZ1, or copZ2, resulted in decreased
      resistance to copper, indicating a major role of the CopA copper exporter in the
      multilayered systems for copper homeostasis. A redundant role of copZ1 and copZ2
      in copper resistance was also indicated by double deletion of these genes. The
      copper-dependent activation of the copA, copZ1, and copZ2 promoters was confirmed
      by lacZ reporter assays, consistent with the coordinated derepression of the
      three transcriptional units. The copZ1 promoter activity showed the highest
      responsiveness to copper and was also induced by excess zinc and nickel.
      Furthermore, zinc-inducible expression observed for the CsoR-regulated genes was
      independent of Zur, recently found to uniquely act as a transcriptional repressor
      of zinc efflux genes. These results implied complicated cross talk between
      homeostasis of multiple transition metals.

PMID- 25592737
TI  - Potent antimicrobial peptides against Legionella pneumophila and its
      environmental host, Acanthamoeba castellanii.
AB  - Legionella pneumophila, the major causative agent of Legionnaires' disease, is
      most often found in the environment in close association with free-living
      amoebae, leading to persistence, spread, biocide resistance, and elevated
      virulence of the bacterium. In the present study, we evaluated the anti
      Legionella and anti-Acanthamoeba activities of three alpha-helical antimicrobial
      peptides (AMPs), namely, NK-2, Ci-MAM-A24, and Ci-PAP-A22, already known for the
      extraordinary efficacy against other microbes. Our data represent the first
      demonstration of the activity of a particular AMP against both the human
      facultative intracellular pathogen L. pneumophila and its pathogenic host,
      Acanthamoeba castellanii. Interestingly, the most effective peptide, Ci-MAM-A24,
      was also found to reduce the Legionella cell number within amoebae. Accordingly,
      this peptide was immobilized on gold surfaces to assess its antimicrobial
      activity. Surfaces were characterized, and activity studies revealed that the
      potent bactericidal activity of the peptide was conserved after its
      immobilization. In the frame of elaborating anti-Legionella surfaces, Ci-MAM-A24
      represents, by its direct and indirect activity against Legionella, a potent
      peptide template for biological control of the bacterium in plumbings. 

PMID- 25592738
TI  - Impacts of sludge retention time on sludge characteristics and membrane fouling
      in a submerged anaerobic-oxic membrane bioreactor.
AB  - Anaerobic-oxic membrane bioreactor (AOMBR) has been proposed as a highly
      effective method in municipal and industrial wastewater treatment. In this study,
      according to the sewage treatment system in a campus, long-term experiments were
      conducted to assess the impacts of the sludge retention time (SRT) on sludge
      characteristics and membrane fouling, and the sludge parameters include biomass
      concentration, particle size distribution, extracellular polymeric substances
      (EPS), soluble microbial products (SMPs), and specific resistance to filtration
      (SRF). Our results clearly demonstrated that SRT was one of the most important
      factors influencing sludge characteristics, and different sludge characteristics
      resulted in different membrane fouling degrees. A better treatment and filtration
      performances were observed at the SRT of 30 days compared to two SRTs of 10 and
      90 days. Among these parameters, SMP had the most significant correlation with
      the membrane fouling rate (dTMP/dt), and it had a negative impact on membrane
      filtration performance. The impact of SRT on membrane fouling process was
      discussed further by filtration models. At 10 days SRT, the complete-standard
      blocking model curve had a comparatively higher goodness-of-fit with the fouling
      process, and at 30 and 90 days SRT, the cake-standard blocking model curve had a
      relatively higher goodness-of-fit with respective fouling process. 

PMID- 25592739
TI  - Synthesis of a beta-CCT-lanthanide conjugate for binding the dopamine
      transporter.
AB  - The development of a beta-CCT-lanthanide conjugate that binds the dopamine
      transporter (DAT) with high affinity (K(d) = 303 nM) is described. Contrast
      agents such as the one described herein could be used as molecular probes to
      directly study the binding of small molecules to receptors such as DAT via MRI,
      PET or SPECT.

PMID- 25592740
TI  - A fast recoiling silk-like elastomer facilitates nanosecond nematocyst discharge.
AB  - BACKGROUND: The discharge of the Cnidarian stinging organelle, the nematocyst, is
      one of the fastest processes in biology and involves volume changes of the highly
      pressurised (150 bar) capsule of up to 50%. Hitherto, the molecular basis for the
      unusual biomechanical properties of nematocysts has been elusive, as their
      structure was mainly defined as a stress-resistant collagenous matrix. RESULTS:
      Here, we characterise Cnidoin, a novel elastic protein identified as a structural
      component of Hydra nematocysts. Cnidoin is expressed in nematocytes of all types
      and immunostainings revealed incorporation into capsule walls and tubules
      concomitant with minicollagens. Similar to spider silk proteins, to which it is
      related at sequence level, Cnidoin possesses high elasticity and fast coiling
      propensity as predicted by molecular dynamics simulations and quantified by force
      spectroscopy. Recombinant Cnidoin showed a high tendency for spontaneous
      aggregation to bundles of fibrillar structures. CONCLUSIONS: Cnidoin represents
      the molecular factor involved in kinetic energy storage and release during the
      ultra-fast nematocyst discharge. Furthermore, it implies an early evolutionary
      origin of protein elastomers in basal metazoans.

PMID- 25592741
TI  - Effects of WIN 55,212-2 (a synthetic cannabinoid CB1 and CB2 receptor agonist) on
      the anticonvulsant activity of various novel antiepileptic drugs against 6 Hz
      induced psychomotor seizures in mice.
AB  - The purpose of this study was to determine the influence of WIN 55,212-2 mesylate
      (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the
      anticonvulsant activity of various second- and third-generation antiepileptic
      drugs (i.e., gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin and
      tiagabine) in the mouse 6 Hz-induced psychomotor seizure model. Psychomotor
      seizures were evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus
      duration) delivered via ocular electrodes. Additionally, total brain
      antiepileptic drug concentrations were measured. Results indicate that WIN (5
      mg/kg, administered i.p.) significantly potentiated the anticonvulsant action of
      gabapentin (P < 0.05) and levetiracetam (P < 0.01), but not that of lacosamide,
      oxcarbazepine, pregabalin or tiagabine in the mouse psychomotor seizure model.
      Moreover, WIN (2.5 mg/kg) had no significant effect on the anticonvulsant
      activity of all tested antiepileptic drugs in the 6 Hz test in mice. Measurement
      of total brain antiepileptic drug concentrations revealed that WIN (5 mg/kg) had
      no impact on gabapentin or levetiracetam total brain concentrations, indicating
      the pharmacodynamic nature of interaction between these antiepileptic drugs in
      the mouse 6Hz model. In conclusion, WIN in combination with gabapentin and
      levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in
      the mouse psychomotor seizure model.

PMID- 25592742
TI  - Souvenaid reduces behavioral deficits and improves social cognition skills in
      frontotemporal dementia: a proof-of-concept study.
AB  - BACKGROUND: SouvenaidTM is a nutraceutical compound thought to positively enhance
      synaptic function. In line with this mechanism of action, SouvenaidTM has been
      shown to improve cognitive function in subjects with mild Alzheimer's disease in
      randomized clinical trials. To date, however, the potential of SouvenaidTM to
      improve cognitive functioning in subjects with other neurodegenerative conditions
      also characterized by synaptic loss has not been explored. OBJECTIVE: To evaluate
      the impact of SouvenaidTM on executive functions, social cognition and behavioral
      disturbances in subjects with the behavioral variant of frontotemporal dementia
      (bv-FTD). METHODS: Twenty-six subjects with bv-FTD were enrolled in the study and
      randomized to SouvenaidTM (125 ml/day) or placebo groups. After 12 weeks,
      subjects were switched between the two groups. All subjects, blinded to
      treatment, underwent clinical and cognitive evaluations at enrollment, after 12
      weeks and after 24 weeks. RESULTS: Treatment with SouvenaidTM was associated with
      a significant reduction of behavioral symptoms and an increase in Theory of Mind
      skills compared to placebo, which both returned to baseline when SouvenaidTM was
      discontinued. SouvenaidTM did not have an effect on executive functions.
      CONCLUSIONS: Our results provide evidence of the potential of SouvenaidTM therapy
      for the treatment of behavioral disturbances and social cognition skills in FTD.

PMID- 25592744
TI  - Corrigendum.

PMID- 25592743
TI  - Overexpression of cystatin C in synovium does not reduce synovitis or cartilage
      degradation in established osteoarthritis.
AB  - INTRODUCTION: Cathepsin K (catK) expression is increased in cartilage, bone and
      synovium during osteoarthritis (OA). To study the role of catK expression and
      elevated cathepsin activity in the synovium on cartilage destruction in
      established OA, we overexpressed cystatin C (cysC), a natural cysteine protease
      inhibitor, in the synovium of rabbit OA joints. METHODS: The ability of cysC to
      inhibit activity of cathepsins in rabbit OA synovium lysates was tested in vitro
      using protease activity assay. In vivo, the tissue localization of recombinant
      adeno-associated virus (rAAV) with LacZ gene after intra-articular injection was
      determined by beta-galactosidase staining of rabbit joints 4 weeks later. To
      inhibit cathepsin activity in the synovium, a rAAV2-encoding cysC was delivered
      intra-articularly into rabbit joints 4 weeks after OA was induced by anterior
      cruciate ligament transection (ACLT). Seven weeks postinjection, endogenous catK
      and cysC levels as well as the vector-derived cysC expression in the synovium of
      normal and OA joints were examined by RNA quantification. Synovial cathepsin
      activity and catK, catB and catL protein levels were determined by activity and
      Western blot analyses, respectively. Synovitis and cartilage degradation were
      evaluated by histopathological scoring. RESULTS: In vitro, the ability of cysC to
      efficiently inhibit activity of purified catK and OA-induced cathepsins in rabbit
      synovial lysates was demonstrated. In vivo, the intra-articular delivery of
      rAAV2/LacZ showed transduction of mostly synovium. Induction of OA in rabbit
      joints resulted in fourfold increase in catK mRNA compared to sham controls while
      no change was detected in endogenous cysC mRNA levels in the synovium. Protein
      levels for catK, catB and catL were also increased in the synovium with a
      concomitant fourfold increase in cathepsin activity. Joints treated with
      rAAV2/cysC showed both detection of vector genomes and vector-derived cysC
      transcripts in the synovium. Production of functional cysC by the vector was
      demonstrated by complete block of cathepsin activity in the synovium. However,
      this did not decrease synovitis, bone sclerosis or progression of cartilage
      degradation. CONCLUSIONS: Increased production of natural cathepsin inhibitor,
      cysC, in OA synovium does not alleviate synovitis or cartilage pathology during a
      preexisting OA.

PMID- 25592746
TI  - Corrigendum.

PMID- 25592745
TI  - Corrigendum.

PMID- 25592747
TI  - Post-synthetic Ti exchanged UiO-66 metal-organic frameworks that deliver
      exceptional gas permeability in mixed matrix membranes.
AB  - Gas separation membranes are one of the lowest energy technologies available for
      the separation of carbon dioxide from flue gas. Key to handling the immense scale
      of this separation is maximised membrane permeability at sufficient selectivity
      for CO2 over N2. For the first time it is revealed that metals can be post
      synthetically exchanged in MOFs to drastically enhance gas transport performance
      in membranes. Ti-exchanged UiO-66 MOFs have been found to triple the gas
      permeability without a loss in selectivity due to several effects that include
      increased affinity for CO2 and stronger interactions between the polymer matrix
      and the Ti-MOFs. As a result, it is also shown that MOFs optimized in previous
      works for batch-wise adsorption applications can be applied to membranes, which
      have lower demands on material quantities. These membranes exhibit exceptional
      CO2 permeability enhancement of as much as 153% when compared to the non
      exchanged UiO-66 mixed-matrix controls, which places them well above the Robeson
      upper bound at just a 5 wt.% loading. The fact that maximum permeability
      enhancement occurs at such low loadings, significantly less than the optimum for
      other MMMs, is a major advantage in large-scale application due to the more
      attainable quantities of MOF needed. 

PMID- 25592748
TI  - Efficacy and adverse events of EMR and endoscopic submucosal dissection for the
      treatment of colon neoplasms: a meta-analysis of studies comparing EMR and
      endoscopic submucosal dissection.
AB  - BACKGROUND: EMR and endoscopic submucosal dissection (ESD) are used frequently to
      remove colon neoplasms. However, the predominance of these procedures has not yet
      been thoroughly explored. OBJECTIVE: To compare the efficacy and adverse events
      related to EMR with those related to ESD for colon neoplasms. DESIGN: A meta
      analysis of 8 studies published between 2005 and 2013. SETTING: Multicenter
      review. PATIENTS: Patients from 8 studies yielding 2299 lesions. INTERVENTIONS:
      EMR or ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection, curative resection,
      recurrence, and adverse events. RESULTS: The pooled odds ratios (OR) (OR [95%
      confidence interval]) for the tumor size, length of the procedure, en bloc
      resection, curative resection, recurrence, additional surgery, delayed bleeding,
      and perforation by ESD versus EMR were 7.38 (6.42-8.34), 58.07 (36.27-79.88),
      6.84 (3.30-14.18), 4.26 (3.77-6.57), 0.08 (0.04-0.17), 2.16 (1.16-4.03), 0.85
      (0.45-1.60), and 4.96 (2.79-8.85), respectively. LIMITATIONS: This analysis
      included only nonrandomized studies. CONCLUSION: The size of the tumor and rate
      of en bloc resection and curative resection were higher, and the rate of
      recurrence was lower in the ESD group versus the EMR group. However, in the ESD
      group, the procedure was longer, and the rate of additional surgery and
      perforation was higher, suggesting that the indications for ESD should therefore
      be rigorously determined in order to avoid such problems.

PMID- 25592749
TI  - The (biological) speciation of vanadate(V) as revealed by (51)V NMR: A tribute on
      Lage Pettersson and his work.
AB  - Four decades of research carried out by Lage Pettersson, his group and his
      coworkers are reviewed, research that has been directed predominantly towards the
      speciation of vanadate and systems containing, along with vanadate and co
      reactants such as phosphate and peroxide, biologically relevant organics. In
      particular, those organics have been addressed that either are (potential)
      ligands for vanadate-derived coordination compounds generated at physiological
      conditions and/or function as constituents in medicinally interesting
      oxidovanadium compounds. Examples for molecules introduced in the context of the
      physiological vanadate-ligand interaction include the dipeptides Pro-Ala, Ala
      Gly, Ala-His and Ala-Ser, the serum constituents lactate and citrate, and the
      nucleobases adenosine and uridine. The speciation in the vanadate-picolinate and
      vanadate-maltol systems is geared towards insulin-enhancing vanadium drugs. The
      speciation as a function of pH, ionic strength and the concentration of vanadate
      and the ligand(s) is based on potentiometric and (51)V NMR investigations, a
      methodical combination that allows reliable access to composition, formation
      constants and, to some extent, also structural details for the manifold of
      species present in aqueous media at physiological pH and beyond. The time frame
      1971 to 2014 is reviewed, emphasizing the interval 1985 to 2006, and thus
      focusing on biologically interesting vanadium systems. Figurative representations
      from the original literature have been included. 

PMID- 25592750
TI  - Low levels of serum ferritin lead to adequate hemoglobin levels and good survival
      in hemodialysis patients.
AB  - BACKGROUND: The optimal level of serum ferritin (s-ft) for anemia control and
      good survival in hemodialysis (HD) patients remains unclear. A 10-year survey was
      performed to clarify the appropriate quantities of s-ft and investigate the
      relationships among s-ft, transferrin saturation (TSAT), and mortality in HD
      patients. METHODS: HD outpatients (n = 125) treated with erythropoiesis
      stimulating agents (ESA) were followed for 10 years. The ESA and low-dose iron
      supplement dosages were adjusted to maintain the hemoglobin (Hb) at 10-11 g/dl,
      according to Japanese guidelines. The Kaplan-Meier method, log-rank tests, and
      the Cox proportional hazards model were used for performing the statistical
      analyses. The interactions among the Hb, s-ft, and TSAT were analyzed using a
      multiple linear regression model. Patients with TSAT >=20% were classified
      according to the s-ft cutoff values: group 1 (s-ft <30 ng/ml); group 2 (s-ft 30
      80 ng/ml); group 3 (s-ft >80 ng/ml); TSAT <20% was a predictor of poor outcome.
      RESULTS: The survival rate in group 2 was significantly higher than that in other
      groups (p = 0.013), and the Cox proportional hazards model analysis showed a good
      effect of low levels of s-ft on patients' survival. The multiple linear
      regression model showed a strong effect of s-ft on the Hb (log [s-ft], beta
      coefficient -0.45: 95% confidence interval -0.65 to -0.26, p < 0.001).
      CONCLUSION: This study revealed that low levels of s-ft have a beneficial effect
      on the outcome of HD patients receiving ESA. Thus, the optimal s-ft level might
      be lower than that established previously for these patients.

PMID- 25592752
TI  - Effect of stab injury in the rat cerebral cortex on temporal pattern of
      expression of neuronal cytoskeletal proteins: an immunohistochemical study.
AB  - Compelling evidence now points to the critical role of the cytoskeleton in
      neurodegeneration. In the present study, using an immunohistochemical approach,
      we have shown that cortical stab injury (CSI) in adult Wistar rats significantly
      affects temporal pattern of expression of neurofilament proteins (NFs), a major
      cytoskeleton components of neurons, and microtubule-associated proteins (MAP2).
      At 3 days post-injury (dpi) most of the NFs immunoreactivity was found in
      pyknotic neurons and in fragmentized axonal processes in the perilesioned cortex.
      These cytoskeletal alterations became more pronounced by 10dpi. At the
      subcellular level CSI also showed significant impact on NFs and MAP-2 expression.
      Thus, at 3dpi most of the dendrites disappeared, while large neuronal somata
      appeared like open circles pointing to membrane disintegration. Conversely, at
      10dpi neuronal perikarya and a few new apical dendrites were strongly labeled.
      Since aberrant NF phosphorylation is a pathological hallmark of many human
      neurodegenerative disorders, as well as is found after stressor stimuli, the
      present results shed light into the expression of neurofilaments after the stab
      brain injury. 

PMID- 25592751
TI  - Effects of culinary spices and psychological stress on postprandial lipemia and
      lipase activity: results of a randomized crossover study and in vitro
      experiments.
AB  - BACKGROUND: Data suggest that culinary spices are a potent, low-calorie modality
      for improving physiological responses to high fat meals. In a pilot study (N = 6
      healthy adults), we showed that a meal containing a high antioxidant spice blend
      attenuated postprandial lipemia by 30% compared to a low spice meal. Our goal was
      to confirm this effect in a larger sample and to consider the influence of acute
      psychological stress on fat metabolism. Further, we used in vitro methods to
      evaluate the inhibitory effect of spices on digestive enzymes. METHODS: In a 2 x
      2, randomized, 4-period crossover design, we compared the effects of 14.5 g
      spices (black pepper, cinnamon, cloves, garlic, ginger, oregano, paprika,
      rosemary, and turmeric) vs. placebo incorporated into a high fat meal (1000 kcal,
      45 g fat), followed by psychological stress (Trier Social Stress Test) vs. rest
      on postprandial metabolism in 20 healthy but overweight adults. Blood was sampled
      at baseline and at 105, 140, 180, and 210 minutes for analysis of triglycerides,
      glucose, and insulin. Additional in vitro analyses examined the effect of the
      spice blend and constituent spices on the activity of pancreatic lipase (PL) and
      secreted phospholipase A2 (PLA2). Mixed models were used to model the effects of
      spices and stress (SAS v9.3). RESULTS: Serum triglycerides, glucose and insulin
      were elevated following the meal (p < 0.01). Spices reduced post-meal
      triglycerides by 31% when the meal was followed by the rest condition (p =
      0.048), but this effect was not present during stress. There was no effect of the
      spice blend on glucose or insulin; however, acute stress significantly increased
      both of these measures (p < 0.01; mean increase of 47% and 19%, respectively).
      The spice blend and several of the individual spices dose-dependently inhibited
      PL and PLA2 activity in vitro. CONCLUSIONS: Inclusion of spices may attenuate
      postprandial lipemia via inhibition of PL and PLA2. However, the impact of
      psychological stress negates any influence of the spice blend on triglycerides,
      and further, increases blood glucose and insulin. TRIAL REGISTRATION:
      ClinicalTrials.gov as NCT00954902 .

PMID- 25592753
TI  - Nonparametric Bayesian clustering to detect bipolar methylated genomic loci.
AB  - BACKGROUND: With recent development in sequencing technology, a large number of
      genome-wide DNA methylation studies have generated massive amounts of bisulfite
      sequencing data. The analysis of DNA methylation patterns helps researchers
      understand epigenetic regulatory mechanisms. Highly variable methylation patterns
      reflect stochastic fluctuations in DNA methylation, whereas well-structured
      methylation patterns imply deterministic methylation events. Among these
      methylation patterns, bipolar patterns are important as they may originate from
      allele-specific methylation (ASM) or cell-specific methylation (CSM). RESULTS:
      Utilizing nonparametric Bayesian clustering followed by hypothesis testing, we
      have developed a novel statistical approach to identify bipolar methylated
      genomic regions in bisulfite sequencing data. Simulation studies demonstrate that
      the proposed method achieves good performance in terms of specificity and
      sensitivity. We used the method to analyze data from mouse brain and human blood
      methylomes. The bipolar methylated segments detected are found highly consistent
      with the differentially methylated regions identified by using purified cell
      subsets. CONCLUSIONS: Bipolar DNA methylation often indicates epigenetic
      heterogeneity caused by ASM or CSM. With allele-specific events filtered out or
      appropriately taken into account, our proposed approach sheds light on the
      identification of cell-specific genes/pathways under strong epigenetic control in
      a heterogeneous cell population.

PMID- 25592754
TI  - Assessments of the transmission of Onchocerca volvulus by Simulium sanctipauli in
      the Upper Denkyira District, Ghana, and the intermittent disappearance of the
      vector.
AB  - Following studies on the transmission of Onchocerca volvulus (Leuckart) by
      Simulium sanctipauli Vajime & Dunbar (Diptera, Simuliidae) in Upper Denkyira
      District in Ghana in 2001 and 2002 (Kutin et al., Med Vet Ent 18:167-173, 2004),
      further assessments were carried out in 2006 and 2013/2014 to determine whether
      transmission parameters had changed since community-directed ivermectin treatment
      (CDTI) began in 1999. There were no marked changes of the transmission
      intensities in 2006. Only slight, but non-significant, reductions were observed
      in infection rates of parous flies with larval stages (L1-L3) of O. volvulus from
      44.1 % (of 1672 parous flies) in 2001/2002 to 42.1 % (506) in 2006 and from 6.5
      to 5.9 % of flies carrying infective larvae in their heads. This suggested that
      there was an ongoing transmission in the area and the parasite reservoir in the
      human population was still high. Unexpectedly, further assessments conducted in
      October 2013 and March and October 2014 revealed that the vector S. sanctipauli
      had apparently disappeared and transmission had ceased, probably as a result of
      intensified gold mining activities along the rivers Ofin and Pra. The water of
      both rivers was extremely turbid, heavily loaded with suspended solids, probably
      preventing the development of blackfly larvae. Some breeding and biting of
      Simulium yahense Vajime & Dunbar was observed in a small tributary of the Pra,
      the Okumayemfuo, which is not affected by gold mining. However, the infection
      rate of flies was low, only 3.7 % of 163 parous flies were infected with first
      stage (L1) larvae of O. volvulus.

PMID- 25592755
TI  - A new species of Choleoeimeria (Apicomplexa: Eimeriidae) parasitic in the rough
      tailed gecko Cyrtopodion scabrum (Sauria: Gekkonidae) in Egypt.
AB  - Coprological examination of 15 samples of the rough-tailed gecko Cyrtopodion
      scabrum collected from Abu Rawash, Giza, Egypt, revealed that 20 % (3/15) were
      passing oocysts of a new Choleoeimeria species. Oocysts of Choleoeimeria scabrumi
      n. sp. are ellipsoidal with a smooth, yellow to orange, bilayered smooth wall,
      measure 26 * 13 MUm, and have a length/width (L/W) ratio of 1.8. Polar granule,
      micropyle and oocyst residuum are absent. Sporocysts are ellipsoidal and 8 * 5
      MUm and the sporocyst wall has two plates joined by a longitudinal suture.
      Stieda, substieda and parastieda bodies are absent. The endogenous development is
      confined to the gallbladder epithelium. Mature meronts are subspheroidal and 11
      13 * 8-10 MUm. Macrogamonts are mostly spheroidal and 12-14 MUm wide, with a
      prominent nucleus in the centre. Microgamonts are irregular in shape, 9-11 * 5-7
      MUm. Based on the morphological features of the oocysts and the endogenous
      development in the gallbladder epithelium, we identified this biliary coccidium
      to be a new species in the genus Choleoeimeria.

PMID- 25592756
TI  - [Blood transfusion - safety of the inventory].
AB  - Over the years, transfusion medicine has been faced to many different problems,
      notably those related to transmission of pathogens. Major progresses have been
      accomplished in terms of security. However, nowadays, the discipline is
      confronted to the day-to-day variability and availability of blood products. More
      and more donors are excluded from blood donation due to various reasons, and the
      donor selection criteria have increased over the years, influencing the number of
      donors able to give blood. This paradox represents one of the constraints that
      transfusion medicine should resolve in the future. This paper presents some
      aspects either common or different between France and Switzerland. 

PMID- 25592757
TI  - Media impact switching surface during an infectious disease outbreak.
AB  - There are many challenges to quantifying and evaluating the media impact on the
      control of emerging infectious diseases. We modeled such media impacts using a
      piecewise smooth function depending on both the case number and its rate of
      change. The proposed model was then converted into a switching system, with the
      switching surface determined by a functional relationship between susceptible
      populations and different subgroups of infectives. By parameterizing the proposed
      model with the 2009 A/H1N1 influenza outbreak data in the Shaanxi province of
      China, we observed that media impact switched off almost as the epidemic peaked.
      Our analysis implies that media coverage significantly delayed the epidemic's
      peak and decreased the severity of the outbreak. Moreover, media impacts are not
      always effective in lowering the disease transmission during the entire outbreak,
      but switch on and off in a highly nonlinear fashion with the greatest effect
      during the early stage of the outbreak. The finding draws the attention to the
      important role of informing the public about 'the rate of change of case numbers'
      rather than 'the absolute number of cases' to alter behavioral changes, through a
      self-adaptive media impact switching on and off, for better control of disease
      transmission. 

PMID- 25592758
TI  - Factors affecting the infectivity of tissues from pigs with classical swine
      fever: thermal inactivation rates and oral infectious dose.
AB  - Outbreaks of classical swine fever are often associated with ingestion of pig
      meat or products derived from infected pigs. Assessment of the disease risks
      associated with material of porcine origin requires knowledge on the likely
      amount of virus in the original material, how long the virus may remain viable
      within the resulting product and how much of that product would need to be
      ingested to result in infection. Using material from pigs infected with CSFV, we
      determined the viable virus concentrations in tissues that comprise the majority
      of pork products. Decimal reduction values (D values), the time required to
      reduce the viable virus load by 90% (or 1 log10), were determined at temperatures
      of relevance for chilling, cooking, composting and ambient storage. The rate of
      CSFV inactivation varied in different tissues. At lower temperatures, virus
      remained viable for substantially longer in muscle and serum compared to lymphoid
      and fat tissues. To enable estimation of the temperature dependence of
      inactivation, the temperature change required to change the D values by 90% (Z
      values) were determined as 13  degrees C, 14  degrees C, 12  degrees C and 10 
      degrees C for lymph node, fat, muscle and serum, respectively. The amount of
      virus required to infect 50% of pigs by ingestion was determined by feeding
      groups of animals with moderately and highly virulent CSFV. Interestingly, the
      virulent virus did not initiate infection at a lower dose than the moderately
      virulent strain. Although higher than for intranasal inoculation, the amount of
      virus required for infection via ingestion is present in only a few grams of
      tissue from infected animals.

PMID- 25592759
TI  - Epidemiological analysis of the dynamic and diversity of Salmonella spp. in five
      German pig production clusters using pheno- and genotyping methods: an
      exploratory study.
AB  - An exploratory study in five conventional pig production clusters was carried out
      to investigate the dynamic and diversity of Salmonella spp. within different
      production stages and sample site categories (pooled feces, direct and non-direct
      environment). Observing two production cycles per production cluster, a total of
      1276 samples were collected along the pig production chain. Following a
      microbiological examination via culture, 2246 subcultures were generated out of
      285 Salmonella positive samples and analysed by pheno- and genotyping methods.
      Based on a combination of serotyping, MLVA (multiple-locus variable-number tandem
      repeat (VNTR) analysis), PFGE (pulse-field gel electrophoresis) and MLST
      (multilocus sequence typing), an amount of 22.3% Salmonella positive samples were
      characterized in clonal lineages and its variants. Within each production
      cluster, one main clonal lineage could be identified and persisted over both
      production cycles with a large diversity of variants and a wide distribution in
      sample site categories and production stages. Results underline the importance of
      biosecurity with emphasis on the environment to prevent persistence and
      circulation of Salmonella within herds. Furthermore, the combined implementation
      of MLVA, PFGE and MLST with conventional culture techniques for isolate
      classification could be successfully applied as an effective and valuable tool
      for identifying similar pattern of Salmonella occurrence within pig production
      clusters. 

PMID- 25592761
TI  - Ewing's sarcoma: dural metastases after intracranial hemorrhage.
AB  - Ewing's sarcoma (ES) is a primary malignant tumor of the mesenchymal tissue of
      bone in children and young adults. Central nervous system metastases of ES are
      rarely seen. In this paper, we report a case of ES that progressed with dural
      metastases after spontaneous intracerebral hemorrhage.

PMID- 25592760
TI  - Genetic diversity of the VP7, VP4 and VP6 genes of Korean porcine group C
      rotaviruses.
AB  - Porcine group C rotaviruses (RVCs) are considered important pathogens due to
      their economic impact on pig industry and may also cross the host species barrier
      toward humans. Unlike RVA, however, genetic and phylogenetic data on RVCs from
      pigs and other host species are scarce. In the present study, full-length ORF
      sequences of 26 VP7, 9 VP4 and 9 VP6 genes of Korean porcine RVC strains were
      compared with those of other known RVC strains by phylogenetic analyses and
      pairwise identity frequency graphs. Applying the established 85% nucleotide
      identity cut-off value for RVC VP7 classification, the 26 Korean porcine RVC
      strains belonged to the G1, G3, G6 and G7 genotypes. Although more complete RVC
      VP4 sequences are warranted before a definitive cut-off value could be
      determined, a provisional 83% nucleotide cut-off value proposed for RVC VP4
      classification resulted in 7 P-genotypes, 5 of which possessed porcine RVC
      strains. A 90% nucleotide cut-off value for VP6 divided RVC strains into 7 I
      genotypes, 5 of which had porcine RVC strains. G/P/I-genotype comparisons
      suggested the occurrence of rather frequent reassortment events among Korean
      porcine RVC strains, and strong geographical differences in the distribution of
      RVC G-genotypes worldwide. Our data indicate that a large genetic diversity
      exists among porcine RVC strains. For the final genotype determination of each
      gene segment, more intensified epidemiological studies on animal and human RVC
      strains throughout the world are needed. 

PMID- 25592763
TI  - Acute kidney injury after aortic valve replacement: incidence, risk factors and
      outcomes.
AB  - The occurrence of acute kidney injury (AKI) following aortic valve replacement
      (AVR) has very serious clinical implications and has therefore been the focus of
      several studies. The authors report the results of previous studies evaluating
      both transcatheter AVR (TAVR) and indirectly surgical AVR (SAVR) through looking
      at cardiopulmonary bypass (CPB) cardiac surgeries, and identify the incidence,
      predictors and outcomes of AKI following AVR. In most studies, AKI was defined
      using the Risk, Injury, Failure, Loss and End Stage, Valve Academic Research
      Consortium (modified Risk, Injury, Failure, Loss and End Stage) or Valve Academic
      Research Consortium-2 (Acute Kidney Injury Network) AKI classification criteria.
      Twelve studies including more than 90,000 patients undergoing cardiac surgery on
      CPB were considered as well as 26 studies with more than 6000 patients undergoing
      TAVR. Depending on the definition used, AKI occurred in 3.4-43% of SAVR cases
      with up to 2.5% requiring dialysis, and in 3.4-57% of TAVR cases. Factors
      identified as independent predictors of AKI were: baseline kidney failure,
      EUROSCORE, diabetes mellitus, hypertension, chronic obstructive pulmonary
      disease, anemia, peripheral vascular disease, heart failure, surgical priority,
      CPB time, reoperation, use of intra-aortic balloon pump, need for re-exploration,
      contrast agent volume, transapical access, blood transfusion, postoperative
      thrombocytopenia, postoperative leukocytosis as well as demographic variables
      such as age and female gender. The 30-day mortality rate for patients with AKI
      following SAVR ranged from 5.5 to 46% and was 3- to 16-times higher than in those
      without AKI. Similarly, patients who developed AKI after TAVR had a mortality
      rate of 7.8-29%, which was two- to eight-times higher than those who did not
      suffer from AKI. AKI confers up to a fourfold increase in 1-year mortality.
      Finally, hospital length of stay was significantly increased in patients with AKI
      in both SAVR and TAVR groups, with increases up to 3- and 2.5-times,
      respectively. 

PMID- 25592765
TI  - Cochlear malformation and sensorineural hearing loss in the Walker-Warburg
      Syndrome.

PMID- 25592762
TI  - High crude violacein production from glucose by Escherichia coli engineered with
      interactive control of tryptophan pathway and violacein biosynthetic pathway.
AB  - BACKGROUND: As bacteria-originated crude violacein, a natural indolocarbazole
      product, consists of violacein and deoxyviolacein, and can potentially be a new
      type of natural antibiotics, the reconstruction of an effective metabolic pathway
      for crude violacein (violacein and deoxyviolacein mixture) synthesis directly
      from glucose in Escherichia coli was of importance for developing industrial
      production process. RESULTS: Strains with a multivariate module for varied
      tryptophan productivities were firstly generated by combinatorial knockout of
      trpR/tnaA/pheA genes and overexpression of two key genes trpEfbr /trpD from the
      upstream tryptophan metabolic pathway. Then, the gene cluster of violacein
      biosynthetic pathway was introduced downstream of the generated tryptophan
      pathway. After combination of these two pathways, maximum crude violacein
      production directly from glucose by E. coli B2/pED+pVio was realized with a titer
      of 0.6+/-0.01 g L(-1) in flask culture, which was four fold higher than that of
      the control without the tryptophan pathway up-regulation. In a 5-L bioreactor
      batch fermentation with glucose as the carbon source, the recombinant E. coli
      B2/pED+pVio exhibited a crude violacein titer of 1.75 g L(-1) and a productivity
      of 36 mg L(-1) h(-1), which was the highest titer and productivity reported so
      far under the similar culture conditions without tryptophan addition. CONCLUSION:
      Metabolic pathway analysis using 13C labeling illustrated that the up-regulated
      tryptophan supply enhanced tryptophan metabolism from glucose, whereas the
      introduction of violacein pathway drew more carbon flux from glucose to
      tryptophan, thereby contributing to the effective production of crude violacein
      in the engineered E. coli cell factory.

PMID- 25592764
TI  - Metabolic syndrome is associated with atrial electrical and mechanical
      dysfunction.
AB  - OBJECTIVE: In this study, we aimed to investigate the left atrial (LA) electrical
      and mechanical functions in patients with metabolic syndrome (MetS). SUBJECTS AND
      METHODS: The study population consisted of 87 patients with MetS and 67 controls.
      Intra-atrial and interatrial electromechanical delays (EDs) were measured with
      tissue Doppler imaging. P-wave dispersion (Pd) was calculated from the 12-lead
      electrocardiograms. LA volumes were measured echocardiographically by the biplane
      area-length method. RESULTS: Intra-atrial and interatrial EDs and Pd were
      significantly higher in patients with MetS (10.3 +/- 6.3, 21.0 +/- 11.5 and 41.7
      +/- 10.8) than in controls (7.4 +/- 5.5, 12.3 +/- 10.4 and 29.2 +/- 7.4; p =
      0.003, p < 0.001 and p < 0.001, respectively). The LA preatrial contraction
      volume and active emptying volumes were higher in this population, but the LA
      passive emptying fraction was lower. In the multivariate linear regression
      analysis, the presence of MetS, LA active emptying volume and left ventricular
      early diastolic (E) wave velocity/late diastolic (A) wave velocity (E/A) ratios
      were independent correlates of interatrial ED (p = 0.002, p = 0.001 and p =
      0.025, respectively). CONCLUSIONS: This study showed that intra-atrial and
      interatrial EDs and Pd were prolonged and LA mechanical functions were impaired
      in patients with MetS.

PMID- 25592766
TI  - Evaluation of melanoma antigen (MAGE) gene expression in human cancers using The
      Cancer Genome Atlas.
AB  - Melanoma antigen (MAGE) cancer-testis (CT) (or cancer-germline) genes are
      frequently over-expressed in cancer. However, the types of cancer in which the
      MAGE genes are over-expressed and the effect of over-expression on outcomes have
      been difficult to ascertain, and their relevance to progression is unclear. We
      queried transcriptomic and survival data from 26 cancer studies through the cBio
      Cancer Genomics Portal (www.cbioportal.org) to investigate dysregulation of 34
      MAGE genes in cancer. MAGE genes are dysregulated in many cancers. Up to 44% of
      samples had over-expression of 22 Type 1 MAGE, which are not expressed in most
      normal tissues, or dysregulation of 12 Type 2 MAGE genes, which are expressed in
      normal tissues. Dysregulation of specific MAGE genes correlated with reduced
      overall survival in four cancer types (brain low grade gliomas, renal clear cell
      carcinomas, head and neck squamous cell carcinomas, and uterine corpus
      endometrioid carcinomas), with weaker correlations in four additional cancer
      types. This study demonstrates (1) the value of cancer-germline antigen
      expression profiling as a complement to mutation analysis for prognosis in
      cancer; (2) that over-expression of MAGE genes in a subset of cancers is
      associated with reduced survival; and (3) that patterns of MAGE expression could
      inform individualized treatment in cancer.

PMID- 25592767
TI  - Disturbing the histone code in leukemia: translocations and mutations affecting
      histone methyl transferases.
AB  - Leukemia is characterized by increased numbers of blasts originating from
      transformed early hematopoietic stem and progenitor cells. Genetic alterations
      are widely recognized as the main drivers of oncogenic transformation. Of
      considerable interest are mutations affecting the writers of epigenetic marks. In
      this review, we focus on histone methyltransferases--enzymes that catalyze the
      methylation of lysine residues in core histones. Histone methylation is a tightly
      controlled mechanism that is responsible for both activating as well as
      repressing gene expression in a site-specific manner, depending on which lysine
      residue is methylated. Histone methyltransferases, including MLL1, DOT1L, EZH2,
      and SETD2 are recurrently deregulated in human leukemia, either directly by gene
      mutations or balanced translocations, or indirectly as components of protein
      complexes that are disturbed in leukemia due to alterations of the other
      components in these complexes. Several small molecule inhibitors of histone
      methyltransferases are currently being clinically evaluated for their therapeutic
      potential in human leukemia. These drugs reverse some of the adverse effects of
      aberrant histone methylation, and can induce differentiation and cell death in
      leukemic blasts.

PMID- 25592768
TI  - Putative functional variants of XRCC1 identified by RegulomeDB were not
      associated with lung cancer risk in a Korean population.
AB  - The Encyclopedia of DNA elements (ENCODE) project revealed that nearby or
      distantly located non-coding DNA regulates the expression of coding genes.
      RegulomeDB (http://regulome.stanford.edu) is a new database that can be used to
      predict whether a variant affects transcription factor binding and gene
      expression. We investigated the association between lung cancer risk and
      potentially functional polymorphisms of XRCC1 that were selected using RegulomeDB
      in a Korean population. A total of 185 polymorphisms of XRCC1 were evaluated
      using RegulomeDB. Strong evidence suggested that 10 polymorphisms, from among the
      185, affected XRCC1 expression with scores of 1a-1f that were based on the
      RegulomeDB scoring system. The rs2854510 polymorphism was rare in Asians (minor
      allele frequency < 0.05). Eight polymorphisms were in strong linkage
      disequilibrium (LD). The rs2854509 polymorphism, which was one of the 8
      polymorphisms in LD, and rs7248167, which was not in the LD block, were genotyped
      in 610 lung cancer patients and 607 age- and sex-matched controls. Additionally,
      four polymorphisms of XRCC1 (rs25487, rs25489, rs1799782, and rs3213245), which
      were investigated with regard to their association with lung cancer risk in
      previous studies, were also genotyped. Two polymorphisms (rs2854509 and
      rs7248167) that were predicted to affect XRCC1 expression based on their
      RegulomeDB scores were not associated with lung cancer risk (P = 0.31 and 0.93,
      respectively). When stratified according to age, gender, smoking status, and
      tumor histology, the two polymorphisms of XRCC1 were not associated with lung
      cancer risk. Among the four polymorphisms that were previously studied, only
      rs25489 of XRCC1 was significantly associated with lung cancer risk (dominant
      model, adjusted odds ratio = 0.61, 95% confidence interval = 0.46-0.83, P =
      0.002). Although RegulomeDB is an attractive tool for predicting the regulatory
      potential of variants, the two polymorphisms that were selected using RegulomeDB
      were not associated with lung cancer risk.

PMID- 25592769
TI  - Risk factors for herpes zoster in a large cohort of unvaccinated older adults: a
      prospective cohort study.
AB  - We analysed data from a prospective cohort of 255,024 adults aged ?45 years
      recruited from 2006-2009 to identify characteristics associated with a zoster
      diagnosis. Diagnoses were identified by linkage to pharmaceutical treatment and
      hospitalization records specific for zoster and hazard ratios were estimated.
      Over 940,583 person-years, 7771 participants had a zoster diagnosis; 253 (3.3%)
      were hospitalized. After adjusting for age and other factors, characteristics
      associated with zoster diagnoses included: having a recent immunosuppressive
      condition [adjusted hazard ratio (aHR) 1.58, 95% confidence interval (CI) 1.32
      1.88], female sex (aHR 1.36, 95% CI 1.30-1.43), recent cancer diagnosis (aHR
      1.35, 95% CI 1.24-1.46), and severe physical limitation vs. none (aHR 1.33, 95%
      CI 1.23-1.43). The relative risk of hospitalization for zoster was higher for
      those with an immunosuppressive condition (aHR 3.78, 95% CI 2.18-6.55), those
      with cancer (aHR 1.78, 95% CI 1.24-2.56) or with severe physical limitations (aHR
      2.50, 95% CI 1.56-4.01). The novel finding of an increased risk of zoster
      diagnoses and hospitalizations in those with physical limitations should prompt
      evaluation of the use of zoster vaccine in this population.

PMID- 25592771
TI  - The protective effect of erythropoietin on the retina.
AB  - Erythropoietin (Epo) was once considered to be a regulator of erythropoiesis by
      controlling the apoptosis, proliferation and differentiation of erythroid
      precursor cells over an extended period of time. However, the expression of Epo
      and Epo receptor (Epo-R) occurs in the brain and retina in addition to the
      kidney. These expression behaviors lead to physiological effects in addition to
      hematocrit elevation. In this review we discuss the protective effect of Epo on
      retinal cells.

PMID- 25592772
TI  - Magnetic Resonance Imaging and 3-dimensional Computed Tomographic Angiography for
      Conservative Management of Proximal Interstitial Pregnancy by Hysteroscopic
      Resection After Transcatheter Arterial Chemoembolization.
AB  - Ectopic pregnancy implanted in the interstitial portion of the fallopian tube is
      a rare potentially life-threatening disorder. A case of unruptured interstitial
      pregnancy with prominent neovascularization in a 37-year-old woman was precisely
      localized in the proximal interstitial portion of the fallopian tube with a
      dilated proximal tubal ostium by magnetic resonance imaging and 3-dimensional
      computed tomographic angiography. After devascularization by transcatheter
      arterial chemoembolization, hysteroscopic resection of the interstitial
      gestational products was performed with single-port laparoscopic assistance.
      Postoperatively, 3 rescue doses of systemic methotrexate were administered to
      accelerate the resolution of gestational products followed by uneventful
      recovery. The uterine wall structure around the interstitial portion was well
      preserved at the cesarean delivery in the subsequent spontaneous gestation. 

PMID- 25592770
TI  - Activation of the nuclear receptor PPARdelta is neuroprotective in a transgenic
      mouse model of Alzheimer's disease through inhibition of inflammation.
AB  - BACKGROUND: Alzheimer's disease (AD) is a multifactorial disorder associated with
      the accumulation of soluble forms of beta-amyloid (Abeta) and its subsequent
      deposition into plaques. One of the major contributors to neuronal death is
      chronic and uncontrolled inflammatory activation of microglial cells around the
      plaques and their secretion of neurotoxic molecules. A shift in microglial
      activation towards a phagocytic phenotype has been proposed to confer benefit in
      models of AD. Peroxisome proliferator activator receptor delta (PPARdelta) is a
      transcription factor with potent anti-inflammatory activation properties and
      PPARdelta agonism leads to reduction in brain Abeta levels in 5XFAD mice. This
      study was carried out to elucidate the involvement of microglial activation in
      the PPARdelta-mediated reduction of Abeta burden and subsequent outcome to
      neuronal survival in a 5XFAD mouse model of AD. METHODS: 5XFAD mice were orally
      treated with the PPARdelta agonist GW0742 for 2 weeks. The brain Abeta load,
      glial activation, and neuronal survival were assessed by immunohistochemistry and
      quantitative PCR. In addition, the ability of GW0742 to prevent direct neuronal
      death as well as inflammation-induced neuron death was analyzed in vitro.
      RESULTS: Our results show for the first time that a short treatment period of
      5XFAD mice was effective in reducing the parenchymal Abeta load without affecting
      the levels of intraneuronal Abeta. This was concomitant with a decrease in
      overall microglial activation and reduction in proinflammatory mediators.
      Instead, microglial immunoreactivity around Abeta deposits was increased.
      Importantly, the reduction in the proinflammatory milieu elicited by GW0742
      treatment resulted in attenuation of neuronal loss in vivo in the subiculum of
      5XFAD mice. In addition, whereas GW0742 failed to protect primary neurons against
      glutamate-induced cell death, it prevented inflammation-induced neuronal death in
      microglia-neuron co-cultures in vitro. CONCLUSIONS: This study demonstrates that
      GW0742 treatment has a prominent anti-inflammatory effect in 5XFAD mice and
      suggests that PPARdelta agonists may have therapeutic utility in treating AD.

PMID- 25592773
TI  - Quorum sensing triggers the stochastic escape of individual cells from
      Pseudomonas putida biofilms.
AB  - The term 'quorum sensing' (QS) is generally used to describe the phenomenon that
      bacteria release and perceive signal molecules to coordinate cooperative
      behaviour in response to their population size. QS-based communication has
      therefore been considered a social trait. Here we show that QS signals (N-acyl
      homoserine lactones, AHLs) are stochastically produced in young biofilms of
      Pseudomonas putida and act mainly as self-regulatory signals rather than inducing
      neighbouring cells. We demonstrate that QS induces the expression of putisolvin
      biosurfactants that are not public goods, thereby triggering asocial motility of
      induced cells out of microcolonies. Phenotypic heterogeneity is most prominent in
      the early stages of biofilm development, whereas at later stages behaviour
      patterns across cells become more synchronized. Our findings broaden our
      perspective on QS by showing that AHLs can control the expression of asocial
      (self-directed) traits, and that heterogeneity in QS can serve as a mechanism to
      drive phenotypic heterogeneity in self-directed behaviour. 

PMID- 25592776
TI  - Dalton Discussion 14 - advancing the chemistry of the f-elements, 28-30 July
      2014, Edinburgh.

PMID- 25592775
TI  - A novel bispidinone analog induces S-phase cell cycle arrest and apoptosis in
      HeLa human cervical carcinoma cells.
AB  - 2,4,6,8-(3)-Tetranitrophenyl-3,7-diazabicyclo[3.3.1]nonan-9-one (B16), a
      bispidinone analog, was synthesized to investigate its effects on cell viability,
      the cell cycle, and apoptotic pathways in HeLa human cervical cancer cells. B16
      decreased the percentage of viable cells in WST-8 assays, and morphological
      changes associated with apoptotic cell death were observed, including cell
      shrinkage and disruption. Annexin V-FITC/PI dual staining assays showed that B16
      significantly increased the early apoptosis of HeLa cells after 24 h of
      treatment. Moreover, DNA content analysis and [3H]-thymidine incorporation assays
      showed that B16 induced S-phase cell cycle arrest and inhibited DNA replication
      after 24 h of treatment. Following treatment with 25 uM of B16, an increase in
      reactive oxygen species and a decrease in mitochondrial membrane potential were
      observed by flow cytometry. In addition, the expression levels of caspase cascade
      and Bcl-2 family proteins determined by western blotting suggested that the
      induction of apoptosis by B16 was associated with a caspase- and mitochondrial
      dependent pathway in HeLa cells. In conclusion, B16 induced early apoptosis and S
      phase cell cycle arrest in HeLa cells via a caspase- and mitochondrial-dependent
      pathway.

PMID- 25592774
TI  - Deconstructing the differences: a comparison of GBD 2010 and CHERG's approach to
      estimating the mortality burden of diarrhea, pneumonia, and their etiologies.
AB  - BACKGROUND: Pneumonia and diarrhea are leading causes of death for children under
      five (U5). It is challenging to estimate the total number of deaths and cause
      specific mortality fractions. Two major efforts, one led by the Institute for
      Health Metrics and Evaluation (IHME) and the other led by the World Health
      Organization (WHO)/Child Health Epidemiology Reference Group (CHERG) created
      estimates for the burden of disease due to these two syndromes, yet their
      estimates differed greatly for 2010. METHODS: This paper discusses three main
      drivers of the differences: data sources, data processing, and covariates used
      for modelling. The paper discusses differences in the model assumptions for
      etiology-specific estimates and presents recommendations for improving future
      models. RESULTS: IHME's Global Burden of Disease (GBD) 2010 study estimated 6.8
      million U5 deaths compared to 7.6 million U5 deaths from CHERG. The proportional
      differences between the pneumonia and diarrhea burden estimates from the two
      groups are much larger; GBD 2010 estimated 0.847 million and CHERG estimated
      1.396 million due to pneumonia. Compared to CHERG, GBD 2010 used broader
      inclusion criteria for verbal autopsy and vital registration data. GBD 2010 and
      CHERG used different data processing procedures and therefore attributed the
      causes of neonatal death differently. The major difference in pneumonia
      etiologies modeling approach was the inclusion of observational study data; GBD
      2010 included observational studies. CHERG relied on vaccine efficacy studies.
      DISCUSSION: Greater transparency in modeling methods and more timely access to
      data sources are needed. In October 2013, the Bill & Melinda Gates Foundation
      (BMGF) hosted an expert meeting to examine possible approaches for better
      estimation. The group recommended examining the impact of data by systematically
      excluding sources in their models. GBD 2.0 will use a counterfactual approach for
      estimating mortality from pathogens due to specific etiologies to overcome bias
      of the methods used in GBD 2010 going forward.

PMID- 25592777
TI  - Effect of organic solvents on Li+ ion solvation and transport in ionic liquid
      electrolytes: a molecular dynamics simulation study.
AB  - Molecular dynamics simulations of N-methyl-N-propylpyrrolidinium (pyr13)
      bis(trifluoromethanesulfonyl)imide (Ntf2) ionic liquid [pyr13][Ntf2] doped with
      [Li][Ntf2] salt and mixed with acetonitrile (AN) and ethylene carbonate (EC)
      organic solvents were conducted using polarizable force field. Structural and
      transport properties of ionic liquid electrolytes (ILEs) with 20 and 40 mol % of
      organic solvents have been investigated and compared to properties of neat ILEs.
      Addition of AN and EC solvents to ILEs resulted in the partial displacement of
      the Ntf2 anions from the Li(+) first coordination shell by EC and AN and shifting
      the Li-Ntf2 coordination from bidentate to monodentate. The presence of organic
      solvents in ILE has increased the ion mobility, with the largest effect observed
      for the Li(+) cation. The Li(+) conductivity has doubled with addition of 40 mol
      % of AN. The Li(+)-N(Ntf2) residence times were dramatically reduced with
      addition of solvents, indicating an increasing contribution from structural
      diffusion of the Li(+) cations. 

PMID- 25592779
TI  - Gene regulation: multiple mechanisms of small RNAs.

PMID- 25592778
TI  - Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic
      trimer with new recognition and effector faces.
AB  - Short-chain pentraxins (PTXs), including CRP and SAP, are innate pattern
      recognition receptors that play vital roles in the recognition and elimination of
      various pathogenic bacteria by triggering the classical complement pathway
      through C1q. Similar to antibodies, pentraxins can also activate opsonisation and
      phagocytosis by interacting with Fc receptors (FcRs). Various structural studies
      on human PTXs have been performed, but there are no reports about the crystal
      structure of bony fish pentraxins. Here, the crystal structures of zebrafish PTX
      (Dare-PTX-Ca and Dare-PTX) are presented. Both Dare-PTX-Ca and Dare-PTX are
      cyclic trimers, which are new forms of crystallised pentraxins. The structures
      reveal that the ligand-binding pocket (LBP) in the recognition face of Dare-PTX
      is deep and narrow. Homology modelling shows that LBPs from different Dare-PTX
      loci differ in shape, reflecting their specific recognition abilities.
      Furthermore, in comparison with the structure of hCPR, a new C1q binding mode was
      identified in Dare-PTX. In addition, the FcR-binding sites of hSAP are partially
      conserved in Dare-PTX. These results will shed light on the understanding of a
      primitive PTX in bony fish, which evolved approximately 450 million years ago. 

PMID- 25592780
TI  - Neuroendocrine carcinoma developing in a choledochal cyst.

PMID- 25592781
TI  - Interferon and low doses of methotrexate versus interferon and retinoids in the
      treatment of refractory/relapsed cutaneous T-cell lymphoma.
AB  - OBJECTIVES: Treatment of refractory/relapsed cutaneous T-cell lymphoma (CTCL)
      remains controversial, most studies included a few patients with a short follow
      up. Previously, we performed two small studies employing interferon alpha 2b
      (IFN) combined with low doses of methotrexate (MTX) or retinoids. Thus, we
      conducted an open-label clinical trial to assess the benefit and toxicity of the
      two mentioned regimens in a large number of patients with a longer follow-up of
      the treatment of refractory/relapsed CTCL. PATIENTS AND METHODS: Three-hundred
      and seventy-seven patients with refractory/relapsed, pathologically confirmed,
      CTCL, with advanced stages and at least treated with two previous effective
      regimens in CTCL, were randomized to receive IFN and low doses of MTX compared
      with IFN and all trans-retinoid acid during 6 months; if a complete response (CR)
      was not achieved, treatment was continued until 12 months in both arms. At this
      time, if patient achieves CR, MTX or retinoid was stopped, and the patient
      continues to receive IFN until progression disease or toxicity. One-hundred and
      eight patients received IFN for more than 5 years. RESULTS: Toxicity was minimal
      and well tolerated, no patients needed to modify the administration of IFN
      secondary to toxicity. The overall complete response was achieved 80% in both
      arms. Actuarial curves at 5 years showed that progression-free survival was 60%
      in the IFN/MTX group and 62% in the IFN/retinoids group (P = 0.8) that were not
      statistically different and overall survival (OS) rates were 70 and 67%,
      respectively (P = 0.03). DISCUSSION: Both present schedules showed good tolerance
      and an excellent OS at 5 years, which is better than the other, more expensive
      and toxic, regimens. Considering the indolent course of CTCL, we suggested that
      those regimens, mentioned in this paper, will be regarded as the standard
      therapy, for patients of this setting. CONCLUSION: The use of IFN and retinoids
      or low dose of cytotoxic drugs will be preferred in patients with
      refractory/relapse CTCL, because OS is good and toxicity is minimal.

PMID- 25592783
TI  - Memory instruction interacts with both visual and motoric inhibition of return.
AB  - In the item-method directed forgetting paradigm, the magnitude of inhibition of
      return (IOR) is larger after an instruction to forget (F) than after an
      instruction to remember (R). In the present experiments, we further investigated
      this increased magnitude of IOR after F than after R memory instructions, to
      determine whether this F > R IOR pattern occurs only for the motoric form of IOR,
      as predicted, or also for the visual form. In three experiments, words were
      presented in one of two peripheral locations, followed by either an F or an R
      memory instruction. Then, a target appeared either at the same location as the
      previous word or at the other location. In Experiment 1, participants maintained
      fixation throughout the trial until the target appeared, at which point they made
      a saccade to the target. In Experiment 2, they maintained fixation throughout the
      entire trial and made a manual localization response to the target. The F > R IOR
      difference in reaction times occurred for both the saccadic and manual responses,
      suggesting that memory instructions modify both motoric and visual forms of IOR.
      In Experiment 3, participants made a perceptual discrimination response to report
      the identity of a target while the eyes remained fixed. The F > R IOR difference
      also occurred for these manual discrimination responses, increasing our
      confidence that memory instructions modify the visual form of IOR. We relate our
      findings to postulated differences in attentional withdrawal following F and R
      instructions and consider the implications of the findings for successful
      forgetting.

PMID- 25592782
TI  - Improving statistical inference on pathogen densities estimated by quantitative
      molecular methods: malaria gametocytaemia as a case study.
AB  - BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time
      polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and
      quantitative nucleic acid sequence-based amplification (QT-NASBA) are
      increasingly used to estimate pathogen density in a variety of clinical and
      epidemiological contexts. These methods are often classified as semi
      quantitative, yet estimates of reliability or sensitivity are seldom reported.
      Here, a statistical framework is developed for assessing the reliability
      (uncertainty) of pathogen densities estimated using QMMs and the associated
      diagnostic sensitivity. The method is illustrated with quantification of
      Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of
      pathogen (e.g. gametocyte) densities, and the accompanying diagnostic
      sensitivity, estimated by two contrasting statistical calibration techniques, are
      compared; a traditional method and a mixed model Bayesian approach. The latter
      accounts for statistical dependence of QMM assays run under identical laboratory
      protocols and permits structural modelling of experimental measurements, allowing
      precision to vary with pathogen density. Traditional calibration cannot account
      for inter-assay variability arising from imperfect QMMs and generates estimates
      of pathogen density that have poor reliability, are variable among assays and
      inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach
      assimilates information from replica QMM assays, improving reliability and inter
      assay homogeneity, providing an accurate appraisal of quantitative and diagnostic
      performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes
      traditional techniques in the context of QMM-derived estimates of pathogen
      density, offering the potential to improve substantially the depth and quality of
      clinical and epidemiological inference for a wide variety of pathogens.

PMID- 25592784
TI  - An infant formula toxicity and toxicokinetic feeding study on carrageenan in
      preweaning piglets with special attention to the immune system and
      gastrointestinal tract.
AB  - A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted
      in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive
      days during the preweaning period at carrageenan concentrations of 0, 300, 1000
      and 2250 ppm under GLP guidelines. This study extends the observations in newborn
      baboons (McGill et al., 1977) to piglets and evaluates additional parameters:
      organ weights, clinical chemistry, special gastrointestinal tract stains
      (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and
      evaluation of potential immune system effects. Using validated methods,
      immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T
      cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood
      cytokine evaluations (IL-6, IL-8, IL1beta, TNF-alpha), and immunohistochemical
      staining of the gut for IL-8 and TNF-alpha were conducted. No treatment-related
      adverse effects at any carrageenan concentration were found on any parameter.
      Glucosuria in a few animals was not considered treatment-related. The high dose
      in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of
      exposure for human infants, as affirmed by JECFA and supports the safe use of
      carrageenan for infants ages 0-12 weeks and older and infants with special
      medical needs. 

PMID- 25592786
TI  - Susceptibility of enamel to initial erosion in relation to tooth type, tooth
      surface and enamel depth.
AB  - This study aimed at assessing the susceptibility of different tooth types
      (molar/premolar), surfaces (buccal/lingual) and enamel depths (100, 200, 400 and
      600 MUm) to initial erosion measured by surface microhardness loss (DeltaSMH) and
      calcium (Ca) release. Twenty molars and 20 premolars were divided into
      experimental and control groups, cut into lingual/ buccal halves, and
      ground/polished, removing 100 MUm of enamel. The initial surface microhardness
      (SMH 0 ) was measured on all halves. The experimental group was subjected to 3
      consecutive erosive challenges (30 ml/tooth of 1% citric acid, pH 3.6, 25 
      degrees  C, 1 min). After each challenge, DeltaSMH and Ca release were measured.
      The same teeth were consecutively ground to 200, 400 and 600 MUm depths, and the
      experimental group underwent 3 erosive challenges at each depth. No difference
      was found in SMH 0 between experimental and control groups. Multivariate
      nonparametric ANOVA showed no significant differences between lingual and buccal
      surfaces in DeltaSMH (p = 0.801) or Ca release (p = 0.370). DeltaSMH was
      significantly greater in premolars than in molars (p < 0.05), but not different
      with respect to enamel depth. Ca release decreased significantly with increasing
      depth. Regression between Ca release and DeltaSMH at 100 MUm depth showed lower
      slope and r 2 value, associated with greater Ca release values. At 200-600 MUm
      depths, moderately large r 2 values were observed (0.651-0.830). In conclusion,
      different teeth and enamel depths have different susceptibility to erosion, so
      when Ca release is used to measure erosion, the depth of the test facet in enamel
      should be standardized, whereas this is less important if DeltaSMH is used.

PMID- 25592785
TI  - Demographic, clinical, and laboratory parameters of cystic fibrosis during the
      last two decades: a comparative analysis.
AB  - BACKGROUND: In recent years, patients with cystic fibrosis (CF) have tended to
      experience a longer life expectancy and higher quality of life. In this context,
      the aim of the present study was to evaluate and compare the demographic,
      clinical, and laboratory markers of patients with CF during the last two decades
      at a CF referral center. METHODS: A retrospective study of the demographic,
      clinical, and laboratory markers for CF treatment at a CF referral center was
      performed during two decades: 2000 (DI, 1990-2000, n = 104 patients) and 2010
      (DII, 2000-2010, n = 181 patients). RESULTS: The following variables were less
      common in DI than in DII: (i) pancreatic insufficiency, (ii) meconium ileus,
      (iii) diabetes mellitus, (iv) Burkholderia cepacia colonization, (v) moderate and
      severe Shwachman-Kulczycki score (SKS), (vi) F508del mutation screening, (vii)
      patients without an identified CFTR mutation (class IV, V, or VI mutation),
      (viii) patients above the 10th percentile for weight and height, (ix) restrictive
      lung disease, and (x) older patients (p < 0.01). The following variables were
      more common in DI than in DII: (i) excellent and good SKS, (ii) F508del
      heterozygous status, (iii) colonization by mucoid and nonmucoid Pseudomonas
      aeruginosa, (iv) obstructive lung disease, and (v) minimal time for CF diagnosis
      (p < 0.01). CONCLUSION: Clinical outcomes differed between the two decades.
      Demographic, clinical, and laboratory markers in patients with CF are useful
      tools and should be encouraged in CF referral centers to determine the results of
      CF management and treatment, enabling a better understanding of this disease and
      its clinical evolution. Early diagnosis and management of CF will improve
      patients' quality of life and life expectancy until personalized drug therapy is
      possible for all patients with CF.

PMID- 25592787
TI  - Protecting a billion hearts.

PMID- 25592788
TI  - Embracing dissemination and implementation research in cardiac critical care.

PMID- 25592789
TI  - Detection of subclinical atherosclerosis in peripheral arterial beds with B-mode
      ultrasound: a proposal for guiding the decision for medical intervention and an
      artifact-corrected volumetric scoring index.
AB  - OBJECTIVES: To assess subclinical atherosclerotic cardiovascular disease (ASCVD)
      using B-mode ultrasound, with special emphasis on the incremental value of
      performing imaging in multiple peripheral arteries, and to compare imaging
      findings with traditional risk factors for medical intervention eligibility.
      METHODS: Data from 2 asymptomatic cohorts from India with unknown ASCVD risk
      factors were compared to 2 cohorts from North America with known ASCVD risk
      factors. Carotid and iliofemoral arteries of the Indian cohorts were examined
      with automated ultrasound in a high-pace environment by non-experts. A simplified
      metric of atherosclerotic disease burden (FUster-Narula or FUN Score) was
      developed from 3D imaging data by summing intima-media volume (IMV) over 5-cm
      arterial segments. Effectiveness of ASCVD prevention guidelines to direct therapy
      was compared to results from direct imaging. RESULTS: Of the 941 (mean age 44.27
      +/- 13.76 years, 34% female) enrollees from India, 224 (24%) demonstrated plaques
      in at least 1 of the 4 arterial sites examined; 107 (11%) had plaques in only the
      carotids, 70 (7%) in both the carotids and iliofemoral arteries, and 47 (5%) had
      plaques in only the iliofemoral arteries. Older age and male sex were associated
      with the presence of plaque, but association with systolic blood pressure was not
      observed. Data from 2 North American clinics (n = 481, mean age 59.68 +/- 11.95
      years, 39% female) showed that 203 subjects (42%) had carotid plaque; 82% of whom
      would not have qualified for lipid-lowering therapy under the Adult Treatment
      Panel (ATP) III Guidelines. Using the recently published ATP IV Guidelines, 33%
      of the individuals with carotid plaque would also have failed to qualify for
      treatment. CONCLUSIONS: B-mode ultrasound examination of bilateral iliofemoral
      arteries provided an incremental yield in identifying subclinical atherosclerotic
      disease compared to carotid evaluation alone. Ultrasound examination allowed
      improved identification of individuals who could be targeted for prophylactic
      medical intervention compared to ATP III and ATP IV Guidelines.

PMID- 25592790
TI  - Vascular ultrasound imaging for screening patients at risk for cardiovascular
      events: application from the west to the East.

PMID- 25592791
TI  - Sex differences in acute coronary syndrome in a multiethnic asian population:
      results of the malaysian national cardiovascular disease database-acute coronary
      syndrome (NCVD-ACS) registry.
AB  - BACKGROUND: Sex differences in acute coronary syndrome (ACS) have been well
      studied in major registries and clinical trials in Western populations. Limited
      studies have examined the sex differences in ACS using a large number of Asian
      women as the subjects. OBJECTIVES: The aim was to study the sex differences in
      ACS using the NCVD-ACS (National Cardiovascular Disease Database-Acute Coronary
      Syndrome) registry. METHODS: We analyzed 13,591 ACS patients, of which 75.8% were
      men and 24.2% were women, from March 2006 to February 2010. Data were collected
      on demographic characteristics, risk factors, anthropometrics, treatments,
      procedures, mortalities, and complications. The results were compared among 3
      cohorts of ACS (ST-segment elevation myocardial infarction [STEMI], non-STEMI,
      and unstable angina). RESULTS: Women were older and more likely to have diabetes,
      hypertension, previous heart failure, and cerebral vascular accidents than men
      were. Women were less likely to receive in-hospital administration of aspirin,
      beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor
      blockers, and they were less likely to undergo angiography and percutaneous
      coronary intervention. In STEMI, a significantly lower proportion of women than
      men received primary percutaneous coronary intervention (6.2% vs. 6.7%,
      respectively, p = 0.000) and fibrinolysis (64.4% vs. 74.6%, respectively, p =
      0.000). In addition, with regard to STEMI, women had a significantly higher
      unadjusted in-hospital mortality rate than men did (15.0% vs. 8.1%, respectively,
      p < 0.000). There was no statistically significant in-hospital mortality
      difference between sexes for non-STEMI and unstable angina. After adjustment for
      age and other covariates, a multivariate analysis showed no sex differences in
      the in-hospital mortality in all spectrums of ACS. CONCLUSIONS: Our study showed
      significant sex differences in the demographic characteristics, risk factors,
      treatments, and outcomes of ACS. More importantly, in ACS patients, we found
      evidence of suboptimal treatments and interventions in women versus men. Our
      findings provide an opportunity to narrow the sex gap in the care of women with
      ACS in Malaysia.

PMID- 25592792
TI  - Cost-effectiveness of treatment and secondary prevention of acute myocardial
      infarction in India: a modeling study.
AB  - BACKGROUND: Cardiovascular diseases are the single largest cause of death in
      India, with acute myocardial infarction (AMI) accounting for one-third of all
      heart disease deaths. Although effective treatment is available for AMI, access
      to treatment is dictated by cost and ability to pay. With scarce treatment
      resources, healthcare decisions are guided by local cost-effectiveness, for which
      country-level data are lacking. OBJECTIVES: We calculate the cost-effectiveness
      of policies that expand the use of aspirin, injection streptokinase, beta
      blockers, angiotensin-converting enzyme inhibitors, and statins for the treatment
      and secondary prevention of AMI in India. We also estimate the cost-effectiveness
      of a hypothetical polypill (combining aspirin, beta blockers, angiotensin
      converting enzyme inhibitors, and statins) for secondary prevention. METHODS: We
      conduct cost-effectiveness analyses of AMI treatment and secondary prevention for
      patients with previous coronary heart disease events in India. We estimate
      coronary heart disease events using Framingham risk scores and disease prevalence
      using a cohort ordinary differential model. Other parameter estimates are from
      the literature. Polypill treatment is assumed to cost less than the additive cost
      of all 4 oral medications, but it is not assumed to increase adherence. We
      conduct a Latin hypercube sampling sensitivity analysis on the model parameters.
      RESULTS: Increasing coverage of AMI treatment with aspirin and streptokinase
      would be cost-effective and could avert approximately 335,000 (191,000 to
      503,000) disability-adjusted life years among 30- to 69-year-olds in India.
      Secondary prevention with aspirin and beta-blockers at 80% coverage (and at lower
      rates) would be highly cost-effective, and the addition of angiotensin-converting
      enzyme inhibitors would also be cost-effective. Introducing the polypill
      dominates a strategy of a 4-drug regimen with the aforementioned drugs and
      statins. The cost-effectiveness ratio of 80% coverage with the polypill would be
      $1,690 ($1,220 to $2,410) per disability-adjusted life years averted.
      CONCLUSIONS: Policies expanding both treatment and preventive therapies are cost
      effective, based on gross domestic product per capita comparison. Introducing the
      polypill would be more effective than providing its components separately, even
      without accounting for the likely increase in treatment adherence.

PMID- 25592793
TI  - Evidence for coronary artery calcification screening in the early detection of
      coronary artery disease and implications of screening in developing countries.
AB  - Coronary artery disease (CAD) has become the biggest threat to population health
      all over the world. Although developed countries have witnessed a decline in CAD
      related mortality in recent decades, developing countries are still experiencing
      steadily increasing CAD morbidity and mortality. Coronary artery calcification
      (CAC) is found to be a risk factor of CAD, and the use of CAC scanning may better
      predict CAD and improve evaluation and diagnosis of CAD. We review the major
      studies from developing countries investigating the prevalence and severity of
      CAC, the relationship of CAC and other conventional risk factors, the diagnostic
      accuracy of CAC computed tomography in relation to coronary angiography, and the
      predictive value of CAC scanning for future CAD events. Last, we summarize the
      recommendations on CAC scanning from several developing countries and propose
      future research topics about CAC. 

PMID- 25592794
TI  - Surveillance of noncommunicable diseases by community health workers in Kerala:
      the epidemiology of noncommunicable diseases in rural areas (ENDIRA) study.
AB  - BACKGROUND: India carries the greatest burden of noncommunicable disease (NCD)
      globally. However, there are few contemporary, community-based studies of
      prevalence in India. Given the physician shortages in rural areas, large-scale,
      region-specific studies of NCD using community health workers (CHW) may offer a
      feasible means of NCD surveillance. OBJECTIVES: This study sought to conduct a
      large-scale, population-based, CHW-led study of NCDs in Kerala, India. METHODS:
      In rural Kerala, India, a population of 113,462 individuals was defined
      geographically by 5 panchayats (village councils). The ENDIRA (Epidemiology of
      Noncommunicable Diseases in Rural Areas) study was conducted via accredited
      social health activists (ASHA), who are CHW employed by Kerala state government.
      After training of ASHA, standardized questionnaires were used during 2012 in
      household interviews of individuals >=18 years of age to gather sociodemographic,
      lifestyle, and medical data. RESULTS: ASHA recruited 84,456 adults who were
      included in the analyses (25.4% were below the poverty line). The prevalence of
      NCD was comparable to contemporary studies in India: myocardial infarction (MI)
      1.4%; stroke 0.3%; respiratory diseases 5.0%; and cancer 1.1%. The dietary habits
      were as follows: 84.1% of the population was vegetarian; 15.9% ate meat/fish >=1
      day per week; 4.2% had >=1 alcoholic drink per week; and 8.1% smoked regularly.
      Compared with men, women were older, had lower body mass index, more likely to be
      hypertensive, less likely to smoke or drink alcohol, and have diabetes or
      dyslipidemia (p < 0.0001). NCD were more common in men than women: MI (1.9% vs.
      0.9%); stroke (0.5% vs. 0.3%); cancer (1.2% vs. 0.9%); and respiratory diseases
      (5.9% vs. 4.0%) (p < 0.0001). Age >=65 years, hypertension, diabetes mellitus,
      dyslipidemia, smoking, and male sex were strongly associated with MI and stroke.
      There were high levels of agreement between ASHA and physicians for diagnoses of
      MI, stroke, hypertension, and diabetes. CONCLUSIONS: CHW effectively conducted a
      large-scale prevalence study of NCD in Kerala, including prevalence of risk
      factors. In rural Kerala, traditional risk factors were strongly associated with
      MI and stroke.

PMID- 25592795
TI  - Developing a STEMI system of care for low- and middle-income countries: the STEMI
      India model.

PMID- 25592796
TI  - eICU reduces mortality in STEMI patients in resource-limited areas.

PMID- 25592797
TI  - STEMI care in LMIC: obstacles and opportunities.

PMID- 25592799
TI  - The U.S. prevention of cardiovascular disease guidelines and implications for
      implementation in LMIC.
AB  - The 2013 guidelines for the Prevention of Cardiovascular Disease released by the
      American College of Cardiology and the American Heart Association included
      guidelines of assessment of cardiovascular disease (CVD) risk, lifestyle
      management, management of overweight and obesity, and treatment of blood
      cholesterol. In addition, there were also 2014 guidelines on hypertension
      management released by members appointed to the Eighth Joint National Committee.
      Taken together, these guidelines, though extensively discussed and disseminated
      in the United States, have not been widely recognized beyond the United States,
      nor have their implications been considered for lower- and middle-income
      developing countries. With an estimated 80% of the global burden in CVD occurring
      in developing countries, it is important to develop strategies to adequately
      detect those at increased CVD risk and to manage their risk through lifestyle and
      where appropriate, pharmacologic means. Though certain aspects of each guideline
      may be suitable for implementation globally, including in developing countries,
      other recommendations would be unrealistic for many countries based on local
      epidemiology and resources. CVD prevention priorities can be set using guidance
      from recently published CVD prevention guidelines if appropriately modified to
      the context of lower- and middle-income developing countries. Establishment of
      global CVD prevention standards and rapid adaptation and dissemination of
      clinical guidelines are of paramount importance if we are to make significant
      progress into achieving World Health Organization 2025 goals to reduce the burden
      from CVD and other noncommunicable diseases. 

PMID- 25592800
TI  - World heart federation expert consensus statement on antiplatelet therapy in east
      asian patients with ACS or undergoing PCI.
AB  - Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in
      patients with acute coronary syndromes and in those undergoing percutaneous
      coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC.
      These recommendations are based primarily on large, phase III, randomized,
      controlled trials of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor.
      However, few East Asian patients have been included in the trials to assess the
      use of these agents, particularly the newer agents prasugrel and ticagrelor.
      Additionally, an increasing body of data suggests that East Asian patients have
      differing risk profiles for both thrombophilia and bleeding compared with white
      patients, and that a different 'therapeutic window' of on-treatment platelet
      reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon
      referred to as the 'East Asian paradox' has been described, in which East Asian
      patients have a similar or even a lower rate of ischaemic events after PCI
      compared with white patients, despite a higher level of platelet reactivity
      during DAPT. Recognizing these concerns, the World Heart Federation has
      undertaken this evidence-based review and produced this expert consensus
      statement to determine the antiplatelet treatment strategies that are most
      appropriate for East Asian patients. 

PMID- 25592801
TI  - Management of STEMI in low- and middle-income countries.

PMID- 25592802
TI  - The cochrane heart at global heart.

PMID- 25592798
TI  - Management of NCD in low- and middle-income countries.
AB  - Noncommunicable disease (NCD), comprising cardiovascular disease, stroke,
      diabetes, and chronic obstructive pulmonary disease, are increasing in incidence
      rapidly in low- and middle-income countries (LMICs). Some patients have access to
      the same treatments available in high-income countries, but most do not, and
      different strategies are needed. Most research on noncommunicable diseases has
      been conducted in high-income countries, but the need for research in LMICs has
      been recognized. LMICs can learn from high-income countries, but they need to
      devise their own systems that emphasize primary care, the use of community health
      workers, and sometimes the use of mobile technology. The World Health
      Organization has identified "best buys" it advocates as interventions in LMICs.
      Non-laboratory-based risk scores can be used to identify those at high risk.
      Targeting interventions to those at high risk for developing diabetes has been
      shown to work in LMICs. Indoor cooking with biomass fuels is an important cause
      of chronic obstructive pulmonary disease in LMICs, and improved cookstoves with
      chimneys may be effective in the prevention of chronic diseases. 

PMID- 25592803
TI  - Task-based functional connectivity as an indicator of genetic liability to
      schizophrenia.
AB  - Impaired functional connectivity has been hypothesized as a potential source of
      the cognitive deficits routinely observed in patients with schizophrenia.
      Additionally, these deficits may be manifestations of the genetic liability to
      schizophrenia and present in the non-psychotic first-degree relatives of that
      group. However, no study has examined task-based functional connectivity in
      schizophrenia relatives using independent component analysis (ICA). We employed
      group ICA to test the hypothesis that the unexpressed genetic liability to
      schizophrenia is reflected in the functional connectivity between brain regions
      during a task measuring context processing. We compared 20 schizophrenia patients
      and 32 patients' first-degree relatives to 22 controls demographically matched to
      the patients and 28 controls' relatives, respectively. The group ICA showed
      differential connectivity between patients and controls in a task-related network
      constituting right middle frontal gyrus (MFG) and right posterior parietal lobe.
      A network constituting left MFG and left posterior parietal, which was also
      related to the context processing task, did not differ between groups. These
      findings demonstrate that connectivity abnormalities associated with the genetic
      liability to schizophrenia are most strongly expressed in a right lateralized
      executive fronto-parietal network, and that these abnormalities are linked to
      context processing impairments. 

PMID- 25592805
TI  - Comparison of the effects of quetiapine extended-release and quetiapine immediate
      release on cognitive performance, sedation and patient satisfaction in patients
      with schizophrenia: a randomised, double-blind, crossover study (eXtRa).
AB  - OBJECTIVES: To assess daytime cognitive performance, sedation and treatment
      satisfaction in patients with schizophrenia receiving quetiapine extended release
      (XR) versus quetiapine immediate release (IR). METHODS: Phase IV prospective,
      double-blind, crossover study (NCT01213836). Patients (N=66) with stable
      schizophrenia, treated with XR or IR before study start, were randomised (1:1) to
      treatment with XR followed by IR, or IR followed by XR, at the dose received
      before enrolment (400-750mg). After 10-16days on formulation 1, patients switched
      to formulation 2. Assessments from three post-dose visits (>=5days following
      treatment on each formulation) were analysed. Cognitive performance was measured
      by CogState Cognition testing. Sedation, treatment satisfaction and safety were
      also assessed. RESULTS: 65 patients received treatment (69.2% male; mean age
      37.8years). Daytime cognitive functioning was similar for both groups; adjusted
      mean difference in Attentional Composite Score in XR and IR patients was 0.005
      (p=0.907). Patients receiving XR were less sedated than those receiving IR, (Bond
      Lader visual analogue scale score, mean [SD]: 23.5 [19.0] vs 28.6 [21.4]);
      estimated overall treatment difference: 5.2 (95% CI: 2.3, 8.2; p<0.0009).
      Patients receiving XR reported feeling less sedated than those on IR (Stanford
      Sleepiness Scale, mean [SD]: 2.4 [0.9] vs 2.6 [1.0]); estimated overall treatment
      difference: 0.28 (95% CI: 0.12, 0.43; p<0.0008). Patients reported improved
      overall treatment satisfaction (p=0.0417) and milder side effects (p=0.0035) with
      XR. Safety profile was similar in both groups. CONCLUSION: Daytime cognitive
      performance was similar for both groups. XR was associated with less daytime
      sedation and improved patient satisfaction than IR.

PMID- 25592806
TI  - BMP signalling: agony and antagony in the family.
AB  - Bone morphogenetic proteins (BMPs) are secreted extracellular matrix (ECM)
      associated proteins that regulate a wide range of developmental processes,
      including limb and kidney formation. A critical element of BMP regulation is the
      presence of secreted antagonists that bind and inhibit BMP binding to their
      cognate Ser/Thr kinase receptors at the plasma membrane. Antagonists such as
      Noggin, Chordin, Gremlin (Grem1), and twisted gastrulation-1 (Twsg1) have been
      shown to inhibit BMP action in a range of different cell types and developmental
      stage-specific contexts. Here we review new developments in the field of BMP and
      BMP antagonist biology during mammalian development and suggest strategies for
      targeting these proteins in human disease. 

PMID- 25592804
TI  - Subchronic pharmacological and chronic genetic NMDA receptor hypofunction
      differentially regulate the Akt signaling pathway and Arc expression in juvenile
      and adult mice.
AB  - NMDA receptor (NMDAR) hypofunction is a compelling hypothesis for the
      pathophysiology of schizophrenia, because in part, NMDAR antagonists cause
      symptoms in healthy adult subjects that resemble schizophrenia. Therefore, NMDAR
      antagonists have been used as a method to induce NMDAR hypofunction in animals as
      a pharmacological model of schizophrenia. Serine racemase-null mutant (SR-/-)
      mice display constitutive NMDAR hypofunction due to the lack of d-serine. SR-/-
      mice have deficits in tropomyosin-related kinase receptor (TrkB)/Akt signaling
      and activity regulated cytoskeletal protein (Arc) expression, which mirror what
      is observed in schizophrenia. Thus, we analyzed these signaling pathways in MK801
      sub-chronically (0.15mg/kg; 5days) treated adult wild-type mice. We found that in
      contrast to SR-/- mice, the activated states of downstream signaling molecules,
      but not TrkB, increased in MK801 treated mice. Furthermore, there is an age
      dependent change in the behavioral reaction of people to NMDAR antagonists. We
      therefore administered the same dosing regimen of MK801 to juvenile mice and
      compared them to juvenile SR-/- mice. Our findings demonstrate that
      pharmacological NMDAR antagonism has different effects on TrkB/Akt signaling than
      genetically-induced NMDAR hypofunction. Given the phenotypic disparity between
      the MK801 model and schizophrenia, our results suggest that SR-/- mice more
      accurately reflect NMDAR hypofunction in schizophrenia. 

PMID- 25592807
TI  - Invasive EEG in refractory epilepsy: insertion of subdural grids through linear
      craniectomy reduces complications and remains effective.
AB  - OBJECTIVE: To evaluate our technique of implanting subdural grids by linear
      craniectomy under computer-assisted navigation for invasive
      electroencephalography in medically refractory epilepsy. MATERIAL AND METHOD: We
      report results from our first 38 consecutive patients with medically refractory
      epilepsy who underwent subdural grids implantation by linear craniectomy. For
      each case, a preoperative MRI was performed for navigation followed by a
      postoperative MRI for localization control of the intracranial electrode
      contacts. A linear skin incision, adapted to the depth and type of subdural
      electrode (strip or grid) and compatible with possible subsequent therapeutic
      surgery, was carried out. One or two linear craniectomies (maximal length 6cm,
      width 1cm) were then drilled with a bevel. The dura mater was incised under
      microscopic guidance to avoid opening the arachnoid. The required subdural
      electrodes were then slipped subdurally through each linear craniectomy (letter
      box technique). RESULTS: Forty-one invasive electroencephalographies were
      performed with 28 (68%) bilateral. For all invasive electroencephalographies, at
      least one subdural grid was implanted. Sixty-one subdural grids were implanted in
      total, 52 with 20 contacts and nine with 32 contacts. No cerebrospinal fluid
      leakage, no infection, no neurological deficit and no permanent complications
      were observed. Three subdural grids (5%) were not positioned exactly as planned
      but this had no consequence for the invasive electroencephalography analysis.
      CONCLUSION: The implantation of 61 consecutive subdural grids for invasive
      electroencephalography through linear craniectomies was associated with no
      transient or permanent complications in this population. This letter-box
      technique appears to be practical and safe without limiting explorative efficacy.

PMID- 25592808
TI  - Camels, Cormorants, and Kangaroo Rats: Integration and Synthesis in Organismal
      Biology After World War II.
AB  - During the decades following World War II diverse groups of American biologists
      established a variety of distinctive approaches to organismal biology.
      Rhetorically, organismal biology could be used defensively to distinguish
      established research traditions from perceived threats from newly emerging fields
      such as molecular biology. But, organismal biologists were also interested in
      integrating biological disciplines and using a focus on organisms to synthesize
      levels of organization from molecules and cells to populations and communities.
      Part of this broad movement was the development of an area of research variously
      referred to as physiological ecology, environmental physiology, or ecophysiology.
      This area of research was distinctive in its self-conscious blend of field and
      laboratory practices and its explicit integration with other areas of biology
      such as ecology, animal behavior, and evolution in order to study adaptation.
      Comparing the intersecting careers of Knut Schmidt-Nielsen and George Bartholomew
      highlights two strikingly different approaches to physiological ecology. These
      alternative approaches to studying the interactions of organisms and environments
      also differed in important ways from the organismal biology championed by leading
      figures in the modern synthesis. 

PMID- 25592809
TI  - The Effect of Furosemide Dose Administered in the Out-of-hospital Setting on
      Renal Function Among Patients with Suspected Acute Decompensated Heart Failure.
AB  - BACKGROUND: The most effective dose of prehospital furosemide in acute
      decompensated heart failure (ADHF) has not yet been identified and concerns of
      worsening renal function have limited its use. OBJECTIVE: To assess if
      administering high-dose furosemide is associated with worsening renal function.
      METHODS: The authors conducted a 2-center chart review for patients who presented
      via a single Emergency Medical Service (EMS) from June 5, 2009 through May 17,
      2013. Inclusion criteria were shortness of breath, primarily coded as ADHF, and
      the administration of furosemide prior to emergency department (ED) arrival. A
      total of 331 charts were identified. The primary endpoint was an increase in
      creatinine (Cr) of more than 0.3 mg/dL from admission to any time during hospital
      stay. Exploratory endpoints included survival, length-of-stay (LOS), disposition,
      urine output in the ED, change in BUN/Cr from admission to discharge, and change
      in Cr from admission to 72 hours and discharge. RESULTS: When treated as a binary
      variable, there was no association observed between an increase in Cr of more
      than 0.3 mg/dL and prehospital furosemide dose. Baseline characteristics found to
      be associated with dose were included in the logistic regression model. Lowering
      the dose of prehospital furosemide was associated with higher odds of attaining a
      0.3 mg/dL increase in Cr (adjusted OR = 1.49 for a 20 mg decrease; P = .019).
      There was no association found with any of the exploratory endpoints.
      CONCLUSIONS: Patients who received higher doses of furosemide prehospitally were
      less likely to have an increase of greater than 0.3 mg/dL in Cr during the
      hospital course.

PMID- 25592811
TI  - Comparison of clinical characteristics and laboratory findings of malaria,
      dengue, and enteric fever in returning travelers: 8-year experience at a referral
      center in Tokyo, Japan.
AB  - BACKGROUND: Without specific symptoms, diagnosis of febrile illness in returning
      travelers is challenging. Dengue, malaria, and enteric fever are common causes of
      fever in returning travelers and timely and appropriate treatment is important.
      However, differentiation is difficult without specific diagnostic tests. METHODS:
      A retrospective study was conducted at the National Centre for Global Health and
      Medicine (NCGM) from April 2005 to March 2013. Febrile travelers returning from
      overseas who were diagnosed with dengue, malaria, or enteric fever were included
      in this study. Clinical characteristics and laboratory findings were compared for
      each diagnosis. RESULTS: During the study period, 86 malaria, 85 dengue, and 31
      enteric fever cases were identified. The mean age of the study cohort was 33.1 +/
      12 years and 134 (66.3%) study participants were male. Asia was the most common
      area visited by returning travelers with fevers (89% of dengue, 18.6% of malaria,
      and 100% of enteric fever cases), followed by Africa (1.2% of dengue and 70.9% of
      malaria cases). Clinical characteristics and laboratory findings were
      significantly different among each group with each diagnosis. Decision tree
      models revealed that returning from Africa and CRP levels <10 mg/L were factors
      specific for diagnosis of malaria and dengue fever, respectively. CONCLUSION:
      Clinical manifestations, simple laboratory test results, and regions of travel
      are helpful to distinguish between dengue, malaria, and enteric fever in febrile
      returning travelers with non-specific symptoms.

PMID- 25592812
TI  - Triggered liver regeneration: from experimental model to clinical implications.
AB  - BACKGROUND: Major liver resection is the only therapeutic option for patients
      with malignant liver tumors. However, extended hepatectomy often leads to
      postoperative liver failure, mainly due to insufficient amounts of the remnant
      liver. Recently, selective portal vein occlusion (PVO) has been introduced to
      increase the remnant liver volume. This novel surgical technique initiated a
      progressive development in liver surgery, resulting in a significant increment in
      potential candidates for curative liver resection. SUMMARY: The theoretical basis
      for this great advancement is formed by an understanding of the mechanisms of PVO
      induced liver regeneration, mainly obtained from animal studies. The aim of this
      review is to give a comprehensive overview of the relevant animal models of PVO
      and to discuss the main characteristics of triggered liver regeneration,
      including the induced hemodynamic, morphological and functional alterations as
      well as the underlying molecular mechanisms, which might be of interest in both
      the laboratory and the clinic. Key Messages: Although basic research revealed the
      main characteristics of PVO-triggered liver regeneration within the last decades,
      several important issues regarding the regenerative process remain uncertain. To
      answer these open questions, additional well-designed animal experiments are
      needed in the future, which allow further refinement of this surgical technique.

PMID- 25592810
TI  - Evaluation of streptococcal toxic shock-like syndrome caused by group B
      streptococcus in adults in Japan between 2009 and 2013.
AB  - Infection with Streptococcus agalactiae has long been recognized in infants. In
      recent years, S. agalactiae is an important cause of morbidity and mortality
      among adults and among those with underlying medical condition. Several cases of
      GBS infection and more fulminant disease similar to streptococcal toxic shock
      syndrome have recently been reported. We report here that 19 S. agalactiae
      strains were isolated from streptococcal toxic shock-like syndrome cases
      involving adult patients in Japan between 2009 and 2013. The average age of the
      patients was 66.3 years. At least one underlying disease was present in 47.4%
      (9/19) of the patients. The most prevalent serotype among these strains was Ib.
      All serotype Ib strains belonged to clonal complex 10 and were ciprofloxacin
      resistant. In contrast, all strains were susceptible to penicillin G, ampicillin,
      cefazolin, cefotaxime, imipenem, panipenem, and linezolid. The characteristic
      type distributions of streptococcal toxic shock-like syndrome isolates differed
      between isolates obtained from vaginal swabs of women and infants with invasive
      infections.

PMID- 25592813
TI  - Meta-analysis: superior treatment response in Asian patients with hepatitis C
      virus genotype 6 versus genotype 1 with pegylated interferon and ribavirin.
AB  - OBJECTIVE: Our goal was to systematically and quantitatively assess treatment
      response between Asian patients with hepatitis C virus genotype 6 (HCV-6) and
      hepatitis C virus genotype 1 (HCV-1) treated for 48 weeks with pegylated
      interferon and ribavirin. METHODS: We performed a literature search in MEDLINE
      and EMBASE for 'genotype 6' in August 2013. Additional abstracts from major
      international scientific conferences from 2012 to 2013 were reviewed. Studies
      included were original articles with >=10 treatment-naive Asian HCV-6 patients.
      Exclusion criteria were coinfections with hepatitis B virus, HIV and/or other
      liver diseases. Heterogeneity was defined as a Cochrane Q test with a p value of
      0.10 and an I(2) statistic of >50%. RESULTS of a random-effects model are
      reported. RESULTS: A total of 1,046 (503 HCV-6; 543 HCV-1) patients from 12
      studies were included in the analysis. The pooled sustained virologic response
      (SVR) rate was 80.2% (95% CI 74.3-85.0, Q statistic = 20.87, p < 0.035; I(2) =
      47.3%) for HCV-6 and 62.5% (95% CI 41.9-79.4, Q statistic = 52.41, p < 0.001;
      I(2) = 92.37) for HCV-1 patients. HCV-6 patients had a significantly higher SVR
      rate compared to HCV-1 patients (odds ratio 2.73, 95% CI 1.69-4.41, p < 0.001).
      Approximately one fourth of patients without early virologic response (EVR)
      achieved SVR, regardless of genotype (HCV-1, n = 6/23; HCV-6, n = 4/21).
      CONCLUSIONS: Asian patients with HCV-6 can expect higher SVR rates (~80%) than
      HCV-1 patients (~63%). EVR as a stopping rule is less clear in Asian patients
      with HCV-6 and HCV-1.

PMID- 25592814
TI  - Haplotype analyses of CYP17A1 genetic polymorphisms and coronary artery disease
      in a Uygur population.
AB  - BACKGROUND: The relationship between CYP17A1 genetic polymorphisms and coronary
      artery disease (CAD) remains unclear. The aim of the present study was to assess
      the association between CYP17A1 gene polymorphism and CAD in a Chinese Uygur
      population. METHODS: A total of 493 people including 266 patients and 227
      controls were selected for the present study. All CAD patients and controls were
      genotyped for the same five single nucleotide polymorphisms (SNPs) (rs4919686,
      rs1004467, rs4919687, rs10786712, and rs2486758) by a real-time PCR method.
      RESULTS: The rs4919686, rs1004467, and rs4919687 polymorphisms were found to be
      associated with CAD in genotypes, dominant model, recessive model, and allele
      frequency (rs4919686: all p<0.05, rs1004467: all p <= 0.001, rs4919687: all
      p<0.001); the significant difference was retained (all p<0.05) after adjustment
      for the major confounding factors. The overall distribution of haplotypes
      established by SNP1-SNP4 (in total subjects and men) and SNP1-SNP4-SNP5 (in total
      subjects) were significantly different between the CAD patients and the control
      subjects (p=0.006, men: p=0.026, and p=0.030, respectively). CONCLUSION:
      Polymorphisms rs4919686, rs4919687 and rs1004467 were found to be associated with
      CAD in this Uygur population.

PMID- 25592815
TI  - Ang (1-7) is a modulator of the vasoconstrictor actions of Ang I and Ang II.
AB  - INTRODUCTION: The role of angiotensin (Ang) (1-7) on the vasoconstrictor effect
      induced by angiotensins could be different in the presence of an ACE inhibitor or
      an ARB because Ang II is formed through several pathways. Therefore, the role of
      Ang (1-7) in Ang I and Ang II contraction was evaluated in aortas from Wistar
      rats after 48-hour coronary occlusion treated with captopril or losartan.
      METHODS: Concentration-response curves to Ang I or Ang II were conducted in the
      absence or presence of Ang (1-7) and A779: a) sham group; b) 48-hour coronary
      occlusion; c) treated with captopril or d) losartan (3.1 mg/kg, i.m.). RESULTS:
      Captopril caused a significant increase in the contractile effect of Ang I and
      Ang II, while losartan reduced it. The presence of Ang (1-7) in the captopril
      group showed a reduction of the contraction compared to the sham group, while the
      treatment with losartan did not show a significant difference. Ang (1-7) presents
      effects different from Ang I or Ang II. CONCLUSION: Ang (1-7) showed a modulatory
      role, suggesting Ang I did as well after treatment with an ACE inhibitor but not
      with an AT1 receptor antagonist.

PMID- 25592816
TI  - The intracellular localization and association of porcine Ia-associated invariant
      chain with the MHC class I-related porcine neonatal Fc receptor for IgG.
AB  - The neonatal Fc receptor (FcRn) transports IgG from mother to young and is
      involved in antigen presentation. FcRn is structurally similar to MHC class I,
      but its intracellular trafficking pathway is much more analogous to that of MHC
      class II. Ia-associated invariant chain (Ii) molecules play an additional role in
      directing MHC class II trafficking within the endocytic compartments by physical
      association with MHC class II. This study addresses the question of whether pig
      Ii chain plays this important role in FcRn trafficking to the endoplasmic
      reticulum. Red or green fluorescent protein-fused Ii or FcRn was constructed, and
      the intracellular localization of pig Ii with FcRn was detected using confocal
      microscopy. Immunoprecipitation and western blotting were used to test for their
      association. The results indicate that pig Ii chain specifically interacts with
      both FcRn H chain alone and FcRn-beta2m complex, and the CLIP in Ii was required
      for FcRn-Ii association. A truncated FcRn deletion in the cytoplasmic tail
      changed the intracellular localization of FcRn. However, the truncated FcRn can
      still combine Ii. This indicated that the cytoplasmic tail of FcRn fails to
      affect FcRn association with Ii. These results suggest that association of FcRn
      with Ii chain is relevant, and appreciation of this process is important to the
      understanding of how IgG is transported. 

PMID- 25592817
TI  - Clinical and molecular spectra in galactosemic patients from neonatal screening
      in northeastern Italy: structural and functional characterization of new
      variations in the galactose-1-phosphate uridyltransferase (GALT) gene.
AB  - Classical galactosemia is an autosomal recessive inborn error of metabolism due
      to mutations of the GALT gene leading to toxic accumulation of galactose and
      derived metabolites. With the benefit of early diagnosis by neonatal screening
      and early therapy, the acute presentation of classical galactosemia can be
      prevented. However, despite early diagnosis and treatment, the long term outcome
      for these patients is still unpredictable because they may go on to develop
      cognitive disability, speech problems, neurological and/or movement disorders
      and, in females, ovarian dysfunction. The objectives of the current study were to
      report our experience with a group of galactosemic patients identified through
      the neonatal screening programs in northeastern Italy during the last 30years. No
      neonatal deaths due to galactosemia complications occurred after the introduction
      of the neonatal screening program. However, despite the early diagnosis and
      dietary treatment, the patients with classical galactosemia showed one or more
      long-term complications. A total of 18 different variations in the GALT gene were
      found in the patient cohort: 12 missense, 2 frameshift, 1 nonsense, 1 deletion, 1
      silent variation, and 1 intronic. Six (p.R33P, p.G83V, p.P244S, p.L267R, p.L267V,
      p.E271D) were new variations. The most common variation was p.Q188R (12 alleles,
      31.5%), followed by p.K285N (6 alleles, 15.7%) and p.N314D (6 alleles, 15.7%).
      The other variations comprised 1 or 2 alleles. In the patients carrying a new
      mutation, the biochemical analysis of GALT activity in erythrocytes showed an
      activity of <1%. In silico analysis (SIFT, PolyPhen-2 and the computational
      analysis on the static protein structure) showed potentially damaging effects of
      the six new variations on the GALT protein, thus expanding the genetic spectrum
      of GALT variations in Italy. The study emphasizes the difficulty in establishing
      a genotype-phenotype correlation in classical galactosemia and underlines the
      importance of molecular diagnostic testing prior to making any treatment.

PMID- 25592818
TI  - Identification and characterization of microRNAs by deep-sequencing in Hyalomma
      anatolicum anatolicum (Acari: Ixodidae) ticks.
AB  - Hyalomma anatolicum anatolicum (H.a. anatolicum) (Acari: Ixodidae) ticks are
      globally distributed ectoparasites with veterinary and medical importance. These
      ticks not only weaken animals by sucking their blood but also transmit different
      species of parasitic protozoans. Multiple factors influence these parasitic
      infections including miRNAs, which are non-coding, small regulatory RNA molecules
      essential for the complex life cycle of parasites. To identify and characterize
      miRNAs in H.a. anatolicum, we developed an integrative approach combining deep
      sequencing, bioinformatics and real-time PCR analysis. Here we report the use of
      this approach to identify miRNA expression, family distribution, and nucleotide
      characteristics, and discovered novel miRNAs in H.a. anatolicum. The result
      showed that miR-1-3p, miR-275-3p, and miR-92a were expressed abundantly. There
      was a strong bias on miRNA, family members, and nucleotide compositions at
      certain positions in H.a. anatolicum miRNA. Uracil was the dominant nucleotide,
      particularly at positions 1, 6, 16, and 18, which were located approximately at
      the beginning, middle, and end of conserved miRNAs. Analysis of the conserved
      miRNAs indicated that miRNAs in H.a. anatolicum were concentrated along three
      diverse phylogenetic branches of bilaterians, insects and coelomates. Two
      possible roles for the use of miRNA in H.a. anatolicum could be presumed based on
      its parasitic life cycle: to maintain a large category of miRNA families of
      different animals, and/or to preserve stringent conserved seed regions with
      active changes in other places of miRNAs mainly in the middle and the end
      regions. These might help the parasite to undergo its complex life style in
      different hosts and adapt more readily to the host changes. The present study
      represents the first large scale characterization of H.a. anatolicum miRNAs,
      which could further the understanding of the complex biology of this zoonotic
      parasite, as well as initiate miRNA studies in other related species such as
      Haemaphysalis longicornis and Rhipicephalus sanguineus of human and animal health
      significance. 

PMID- 25592819
TI  - FTO gene variants are not associated with polycystic ovary syndrome in women from
      Southern Brazil.
AB  - BACKGROUND AND AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine
      disorder, presenting polygenic traits as well as determined by environmental
      factors. Given the overlap between PCOS and obesity, we assessed the frequencies
      of SNPs rs9939609 and rs8050136 in intron 1 of the FTO gene and their haplotypes
      in women with PCOS and healthy controls with regular cycles from Southern Brazil
      and investigated their relationship with metabolic traits and endocrine
      parameters. SUBJECTS AND METHODS: The sample comprised 298 women (199 with PCOS
      and 99 non-hirsute women with regular ovulatory cycles). FTO genotyping was done
      by real-time PCR. Haplotypes were constructed from the combination of both
      polymorphisms. Frequencies were inferred using PHASE 2.1.1 software. RESULTS: The
      distribution of rs9939609 (PCOS: 32.6% TT, 45.9% TA, 21.5% AA; controls: 33.3%
      TT, 49.0% TA, 17.7% AA) and rs8050136 (PCOS: 21.7% AA, 43.3% AC, 35.0% CC;
      controls: 14.9% AA, 48.9% AC, 36.2% CC) was similar between groups. The mean age
      of participants was 22.7+/-7.1years. Women with PCOS had significantly higher
      BMI, waist circumference, total testosterone, and FAI vs. controls. In the PCOS
      group, no differences between genotypes and haplotypes were found for clinical
      variables. The presence of at least one risk allele for polymorphisms rs9939609
      and rs8050136 was associated with higher fasting glucose levels. CONCLUSION: Our
      findings indicate that neither the FTO rs9939609 and rs8050136 polymorphisms nor
      its haplotypes are related to PCOS, but suggest an association between the
      presence of risk alleles of SNPs rs9939609 and rs8050136 in FTO and glucose
      levels in women from Southern Brazil.

PMID- 25592820
TI  - Molecular cloning, characterization and expression analysis of complement
      component C8 beta in the orange-spotted grouper (Epinephelus coioides) after the
      Vibrio alginolyticus challenge.
AB  - Complement component C8 beta was a key molecule in the complement system,
      mediating the MAC formation and the bacterial lysis. In this study, the full
      length C8 beta (EcC8 beta) was obtained, containing a 5'UTR of 25 bp, an ORF of
      1764 bp and a 3'UTR of 198 bp. The EcC8 beta gene encoded a protein of 587 amino
      acids with an estimated molecular mass of 65.87 kDa and a predicted isoelectric
      point (pI) of 6.35. The deduced amino acid sequence showed that EcC8 beta
      consisted of the conserved residues and the domains known to be critical for C8
      beta function. The quantitative real-time PCR analysis revealed that EcC8 beta
      transcript was expressed in all the examined tissues, while the strong expression
      was observed in the liver. In addition, complement C3 was the central molecule in
      the complement system, converging the upstream complement signals and mediating
      the MAC assembly pathway, while C8 beta was indispensable for active MAC
      formation. Following the Vibrio challenge, the increased expression of EcC3
      transcript and EcC8 beta transcript was observed in the liver and kidney. These
      results indicated that EcC8 beta may be an important immune-related gene, playing
      an important role in the immune defense against the bacterial infection via the
      complement pathway.

PMID- 25592821
TI  - Mutations in HSP70-2 gene change the susceptibility to clinical mastitis in
      Chinese Holstein.
AB  - To select the molecular markers susceptible to mastitis and reduce the loss
      induced by mastitis, the PCR-SSCP method was adopted to investigate the
      correlation between SNPs of the HSP70-2 gene and mastitis in 103 Chinese
      Holstein. 25 new polymorphisms were detected in this study: 9 SNPs (g.-115 G->A,
      g.-98 T->C, g.117 C->A, g.156 A->C, g.1743 G->A, g.1746 C->T, g.1761 T->G, g.1770
      C->G, g.1877 G->C) were found to be associated with mastitis; 2 key SNPs led to
      amino-acid changes: g.1770 C->G (590 Asp->Glu), g.1877 G->C (626 Gly->Ala). 626
      Gly->Ala affected the protein secondary structure. 3 potential cow HSP70-2
      proteins were found in all the 103 individuals, but predicted three-dimensional
      structures of 3 proteins are the same with each other. It is suggested that 9
      SNPs increase the susceptibility to mastitis due to their low polymorphisms and
      can be used as molecular markers to breed the dairy cows resistant to mastitis.

PMID- 25592822
TI  - DNA damage stress induces the expression of ribosomal protein S27a gene in a p53
      dependent manner.
AB  - The small ribosomal protein RPS27a is known to play a role in the activation of
      cellular checkpoints via p53 which links ribosome biogenesis to cell cycle
      progression. Here, we show that RPS27a gene is a direct transcriptional target of
      p53 and is overexpressed in response to DNA damage. Elevated RPS27a level was
      associated with increased expression of p53 and its target p21(Waf1) gene. The
      RPS27a activity was specifically inhibited in the presence of a dominant negative
      mutant of p53. Down-regulation of ectopically expressed RPS27a by RNA
      interference blocked the activation of p21(waf1) in response to DNA damage. Thus,
      RPS27a appears to be a novel stress sensor in the cell which amplifies p53
      response to arrest cell cycle. 

PMID- 25592823
TI  - Analysis of the crow lung transcriptome in response to infection with highly
      pathogenic H5N1 avian influenza virus.
AB  - The highly pathogenic avian influenza (HPAI) H5N1 virus, currently circulating in
      Asia, causes severe disease in domestic poultry as well as wild birds like crow.
      However, the molecular pathogenesis of HPAIV infection in crows and other wild
      birds is not well known. Thus, as a step to explore it, a comprehensive global
      gene expression analysis was performed on crow lungs, infected with HPAI H5N1
      crow isolate (A/Crow/India/11TI11/2011) using high throughput next generation
      sequencing (NGS) (GS FLX Titanium XLR70). The reference genome of crow is not
      available, so RNA seq analysis was performed on the basis of a de novo assembled
      transcriptome. The RNA seq result shows, 4052 genes were expressed uniquely in
      noninfected, 6277 genes were expressed uniquely in HPAIV infected sample and of
      the 6814 genes expressed in both samples, 2279 genes were significantly
      differentially expressed. Our transcriptome profile data allows for the ability
      to understand the molecular mechanism behind the recent lethal HPAIV outbreak in
      crows which was, until recently, thought to cause lethal infections only in
      gallinaceous birds such as chickens, but not in wild birds. The pattern of
      differentially expressed genes suggest that this isolate of H5N1 virus evades the
      host innate immune response by attenuating interferon (IFN)-inducible signalling
      possibly by down regulating the signalling from type I IFN (IFNAR1 and IFNAR2)
      and type II IFN receptors, upregulation of the signalling inhibitors suppressor
      of cytokine signalling 1 (SOCS1) and SOCS3 and altering the expression of toll
      like receptors (TLRs). This may be the reason for disease and mortality in crows.

PMID- 25592824
TI  - Genetic associations with coronary heart disease: meta-analyses of 12 candidate
      genetic variants.

PMID- 25592825
TI  - Correlation of virtual touch tissue quantification and liver biopsy in a rat
      liver fibrosis model.
AB  - Liver fibrosis assessment is very important to the treatment of chronic liver
      disease. In the present study, Virtual Touch Tissue Quantification (VTQ) and eSie
      TouchTM elasticity imaging techniques were used to examine the rat liver fibrosis
      model. Rat liver fibrosis was induced with thioacetamide and the degree of liver
      fibrosis was determined using pathological diagnosis as a gold standard. The
      right lobe of the liver was also examined with the VTQ and eSie TouchTM
      techniques. The VTQ and serological results were correlated and analyzed. The
      results were compared with those obtained from liver biopsies to investigate the
      accuracy and diagnostic value of eSie TouchTM and VTQ on the classification of
      liver fibrosis in rats. A total of 30 successful modeling cases were obtained,
      with a success rate of 86%. The mean acoustic radiation force impulse (ARFI)
      elastography-VTQ values were 1.08, 1.51, 1.88 and 2.50 m/sec for the normal and
      F1/F2, F3 and F4 fibrosis groups, respectively. A significant correlation (r =
      0.969) was identified between the ARFI measurements and the degree of fibrosis
      assessed by pathological examination (P<0.001). The histological staging results
      correlated with those of the eSie TouchTM elasticity imaging of the biopsy site
      (r = 0.913, P<0.001). The predictive values of ARFI for various stages of
      fibrosis were as follows: F>=1 and 2 - cut-off >1.250 m/sec (when Vs >1.250
      m/sec, the pathological grading was >=F1/F2) [Area under receiver operating
      characteristic (AUROC) = 1.00], F>=3 - cut-off >1.685 m/sec (when Vs >1.685
      m/sec, the pathological grading was >=F3; AUROC = 1.00) and F>=4 - cut-off >2.166
      m/sec (when Vs >2.166 m/sec, the pathological grading is cirrhosis; AUROC =
      1.00). In conclusion, the eSie TouchTM elasticity imaging and VTQ techniques may
      be successfully adopted to assess the extent of liver stiffness. These techniques
      are expected to replace liver biopsy.

PMID- 25592827
TI  - Bronchoscope: beyond the thorax!

PMID- 25592826
TI  - Immunohistochemical and HPV-related features of laryngeal adenosquamous
      carcinoma.
AB  - BACKGROUND: Adenosquamous carcinoma (ASC) of the head and neck is a rare
      malignancy characterized by loco-regional and distant aggressiveness. At
      histology, ASC reveals two distinct, juxtaposed components, squamous cell
      carcinoma (SCC), and true adenocarcinoma. METHODS: The immunohistochemical
      expression of AE3, CK19 and CAM5.2, and HPV infection was tested in a case of
      laryngeal ASC. RESULTS: The patient had no regional lymph node metastases, but
      developed a recurrence in neck soft tissues shortly after primary radical
      surgery. The laryngeal surgical specimen had the typical morphological features
      of ASC. The tumor's squamous and glandular components were both strongly and
      diffusely immunoreactive for AE3 and CK19, whereas CAM5.2 selectively stained
      only the gland-like part. We found no high- or low-risk HPV DNA (28 genotypes) in
      the specimens. The patient underwent salvage extended radical neck dissection and
      received postoperative radio-chemotherapy. At 4-month follow-up control, neck
      recurrence was found. Palliative chemotherapy was instituted. CONCLUSIONS: An
      accurate histological and immunohistochemical diagnosis is mandatory to
      differentiate ASC from conventional SCC. Radical surgical excision is recommended
      for laryngeal ASC. Adjuvant postoperative therapy is administered in most cases,
      but there are no widely accepted indications for these treatments.

PMID- 25592828
TI  - Primary amine recognition in water by a calix[6]aza-cryptand incorporated in
      dodecylphosphocholine micelles.
AB  - Water is a unique solvent and the design of selective artificial hosts that can
      efficiently work in an aqueous medium is a challenging task. It is known that the
      calix[6]tren zinc complex can recognize neutral guests in organic solvents. This
      complex was incorporated into dodecylphosphocholine micelles (DPC) and studied by
      NMR. The incorporated complex is able to extract selectively primary amines from
      the aqueous environment driven by an important hydrophobic effect which also
      affects the selectivity of the complex for these amines. This work shows how the
      incorporation of organo-soluble receptors in micelles can be an elegant and very
      efficient strategy to obtain water compatible nanosized supramolecular
      recognition devices which can be prepared via a straightforward self-assembly
      process. 

PMID- 25592829
TI  - Ultrasound and fluoroscopy are unnecessary for injections into the arthritic hip.
AB  - PURPOSE: We investigated the effectiveness of non-image-guided hip injections.
      METHODS: We retrospectively evaluated 369 intra-articular hip injections in 331
      patients using anatomical landmarks. The percentage and duration of pain relief
      was documented. Hip injections were grouped in responders and nonresponders (50 %
      maximum pain relief as a cut off). RESULTS: In 82% (n = 304) of hip injections,
      patients responded positively and experienced >50 % pain relief. Nonresponders
      had a significantly higher body mass index (p = 0.007). CONCLUSIONS: Hip
      injections using anatomical landmarks are an effective treatment option for
      patients with osteoarthritis of the hip.

PMID- 25592830
TI  - Deltopectoral approach for shoulder arthroplasty: anatomic basis.
AB  - PURPOSE: The deltopectoral approach is a common surgical procedure for shoulder
      arthroplasty. Many surgeons are familiar with this procedure, but certain steps
      are still controversial. This is the case for the management of subscapularis,
      where surgeons must choose between tenotomy and the lesser tuberosity osteotomy.
      METHODS: This article is conceived as a toolkit for the inexperienced surgeons,
      describing our tips and tricks to facilitate final exposure of the glenoid. For
      experienced surgeons, we analysed the tricky portions of the deltopectoral
      approach, comparing them with what is classically reported in the literature.
      RESULTS: We describe an original technic for subscapularis reattachment after
      lesser tuberosity osteotomy in order to improve its stability. The medial part of
      the fragment is secondarily sculpted to obtain a step shape, which will be
      applied against the base of the prosthetic cup in a sort of "corner buttress".
      CONCLUSIONS: Our work, based on our personal experience, confirms that there is
      no preferred single deltopectoral approach but, rather, multiple options. When
      embarking on this "shoulder highway", we encourage surgeons to respect the
      successive anatomic planes, which we believe is the only way to ensure easy and
      atraumatic dissection. KEY POINTS: - The safe plane for going around the humeral
      head and positioning retractors is the plane of the subacromial deltoid bursa. -
      Always stay close to the bone during capsule release, whether on the humeral or
      glenoid side. - Never go medially to the conjoint tendon or its deep face.

PMID- 25592831
TI  - "Sliding angulation osteotomy" for chronic radial head dislocation following
      missed Monteggia injuries.

PMID- 25592832
TI  - Reply to comments on Reito et al.: Repeated metal ion measurements in patients
      with high risk metal-on-metal hip replacement.

PMID- 25592834
TI  - Aberrant activation of AMP-activated protein kinase contributes to the abnormal
      distribution of HuR in amyotrophic lateral sclerosis.
AB  - Distorted mRNA metabolism contributes to amyotrophic lateral sclerosis (ALS). The
      human antigen R (HuR) is a major mRNA stabilizer. We report that abnormal
      localization of HuR was associated with enhanced AMP-activated protein kinase
      (AMPK) activity in the motor neurons of ALS patients. Activation of AMPK changed
      the location of HuR in mouse motor neurons and in a motor neuron cell line via
      phosphorylation of importin-alpha1. Stimulation of the A2A adenosine receptor
      normalized the AMPK-evoked redistribution of HuR. This suggests that aberrant
      activation of AMPK in motor neurons disrupts the normal distribution of HuR,
      which might imbalance RNA metabolism and contribute to ALS pathogenesis. 

PMID- 25592833
TI  - Mortality and cancer in relation to ABO blood group phenotypes in the Golestan
      Cohort Study.
AB  - BACKGROUND: A few studies have shown an association between blood group alleles
      and vascular disease, including atherosclerosis, which is thought to be due to
      the higher level of von Willebrand factor in these individuals and the
      association of blood group locus variants with plasma lipid levels. No large
      population-based study has explored this association with overall and cause
      specific mortality. METHODS: We aimed to study the association between ABO blood
      groups and overall and cause-specific mortality in the Golestan Cohort Study. In
      this cohort, 50,045 people 40- to 70-years old were recruited between 2004 and
      2008, and followed annually to capture all incident cancers and deaths due to any
      cause. We used Cox regression models adjusted for age, sex, smoking,
      socioeconomic status, ethnicity, place of residence, education and opium use.
      RESULTS: During a total of 346,708 person-years of follow-up (mean duration 6.9
      years), 3,623 cohort participants died. Non-O blood groups were associated with
      significantly increased total mortality (hazard ratio (HR) = 1.09; 95% confidence
      interval (CI): 1.01 to 1.17) and cardiovascular disease mortality (HR = 1.15; 95%
      CI: 1.03 to 1.27). Blood group was not significantly associated with overall
      cancer mortality, but people with group A, group B, and all non-O blood groups
      combined had increased risk of incident gastric cancer. In a subgroup of cohort
      participants, we also showed higher plasma total cholesterol and low-density
      lipoprotein (LDL) in those with blood group A. CONCLUSIONS: Non-O blood groups
      have an increased mortality, particularly due to cardiovascular diseases, which
      may be due to the effect of blood group alleles on blood biochemistry or their
      effect on von Willebrand factor and factor VIII levels.

PMID- 25592835
TI  - Hyaluronan inhibits BMP-induced osteoblast differentiation.
AB  - Hyaluronan (HA), one of the major structural extracellular components in
      cartilage, regulates cellular responses via receptors such as CD44. However, the
      direct effects of HA on osteoblastic differentiation has not been studied in
      detail. Here, we investigated the effects of HA (molecular weight: 900-1200 kDa)
      on osteoblastic differentiation that was induced by bone morphogenetic protein
      (BMP) in C2C12 cells (mouse myoblastic cells) and ST2 cells (mouse bone marrow
      cells). BMP-induced osteoblastic differentiation and Smad1/Smad5/Smad8
      phosphorylation were downregulated by HA. Use of the CD44-blocking antibody
      restored HA-induced inhibition of osteoblastic differentiation and
      Smad1/Smad5/Smad8 phosphorylation. Our results indicate that HA inhibits BMP
      induced osteoblastic differentiation through the CD44 receptor.

PMID- 25592836
TI  - Differential membrane expression of Toll-like receptors and intracellular
      cytokine induction in peripheral blood monocytes of patients with chronic kidney
      disease and diabetic nephropathy.
AB  - BACKGROUND: Toll-like receptors (TLRs) are key players in the innate immune
      system whose activation leads to an inflammatory response. Inflammation plays an
      important role in the pathogenesis of chronic kidney disease (CKD) and diabetes
      mellitus. The aim of our study was to assess the proinflammatory state of
      nondialysis CKD patients by evaluating the membrane expression of TLR2 and TLR4
      and the intracellular IL-1beta and IL-6 production in response to the ligand
      Pam3Cys-Ser-(Lys)4 (Pam3CSK4). METHODS: 85 nondialysis CKD patients [mean
      estimated glomerular filtration rate: 34 (17-90) ml/min/1.73 m(2)] were divided
      in 2 groups: 55 nondiabetic CKD patients (CKD group) and 30 patients with
      diabetic nephropathy (DN group). The two groups were compared with 36 healthy
      subjects (control group). TLR2 and TLR4 membrane expression in monocytes and
      Pam3CSK4-induced intracellular production of IL-1beta and IL-6 were assessed by
      flow cytometry. RESULTS: Both patient groups showed increased TLR2 membrane
      expression compared with the control group, both at baseline (p < 0.05 for both)
      and after Pam3CSK4 stimulation (p < 0.05 for both). The DN group exhibited
      significantly higher TLR4 expression at baseline compared to the CKD and control
      groups (p < 0.04 and p < 0.02, respectively). Intracellular IL-1beta and IL-6
      levels at baseline were significantly lower in CKD patients compared to the DN
      and control groups. After Pam3CSK4 stimulation, intracellular IL-1beta and IL-6
      increased in all groups, but were lower in the CKD group versus the control group
      or DN group, which exhibited higher levels than the controls. CONCLUSIONS:
      Nondialysis CKD patients showed significant alterations in TLR2 and TLR4 membrane
      expression, and impaired Pam3CSK4-induced cytokine production in monocytes, a
      phenomenon that is markedly influenced by the presence of diabetes.

PMID- 25592837
TI  - Melanoma characteristics in Brazil: demographics, treatment, and survival
      analysis.
AB  - BACKGROUND: The incidence of melanoma, one of the most aggressive of the skin
      cancers, has been increasing worldwide in the last few decades. Data from Latin
      America and Brazil remain scarce. We aimed to describe the demographic, clinical,
      and histopathological data; therapy characteristics; and survival rates of the
      Brazilian melanoma patient population. RESULTS: We collected and analysed
      retrospective data from 15 years at a tertiary cancer centre. We describe patient
      characteristics and treatment. We calculated survival, and identified the main
      prognostic factors through univariate and multivariate analysis. We analysed a
      total of 1073 patients, with a mean age of 56.7 years. Men and women experienced
      similar prevalence, and 91.2% of patients had white skin. The most prevalent
      subtype was superficial spreading, and the most prevalent anatomic location was
      the trunk (32.2%), followed by the lower extremities (28%). Of all cases, 567
      (52.9%) were assigned to clinical stages I and II, while 382 (32.6%) were stages
      III and IV. Surgery was the main treatment. Sentinel node biopsy was performed in
      373 patients, with 23.8% positivity. Overall actuarial 5-year survival was 67.6%.
      Multivariate analysis showed that gender, serum lactate dehydrogenase (LDH)
      levels at diagnosis; anatomic location, TNM stage, and local recurrence were
      significant prognostic factors. CONCLUSIONS: Overall survival was lower than
      worldwide rates. The main factors influencing survival were similar to those in
      other populations. Local recurrence was independently associated with lower
      survival rates. The high prevalence of advanced cases reinforces the importance
      of strategies to diagnose melanomas in the early stages. There is a need for
      future multi-institutional prospective studies to attain a better understanding
      of possible socioeconomic and other influences on survival among melanoma
      populations in Brazil and Latin America.

PMID- 25592839
TI  - A primer for Leishmania population genetic studies.
AB  - Leishmaniases remain a major public health problem. Despite the development of
      elaborate experimental techniques and sophisticated statistical tools, how these
      parasites evolve, adapt themselves to new environmental compartments and hosts,
      and develop resistance to new drugs remains unclear. Leishmania parasites
      constitute a complex model from a biological, ecological, and epidemiological
      point of view but also with respect to their genetics and phylogenetics. With
      this in view, we seek to outline the criteria, caveats, and confounding factors
      to be considered for Leishmania population genetic studies. We examine how the
      taxonomic complexity, heterozygosity, intraspecific and interspecific
      recombination, aneuploidy, and ameiotic recombination of Leishmania intersect
      with population genetic studies of this parasite. 

PMID- 25592838
TI  - A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2
      receptor interaction with the GIPC1-PDZ-domain.
AB  - Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A
      GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain
      recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C
      terminal segment and we investigate its role in the function of D2R by studying
      the interaction with the PDZ-containing GIPC1 using homology models based on the
      X-ray structures of very closely related analogs: the D3R for the D2R model, and
      the PDZ domain of GIPC2 for GIPC1-PDZ. The mechanism of this interaction was
      investigated with all-atom unbiased molecular dynamics (MD) simulations that
      reveal the role of the membrane in maintaining the helical fold of Hx8, and with
      biased MD simulations to elucidate the energy drive for the interaction with the
      GIPC1-PDZ. We found that it becomes more favorable energetically for Hx8 to adopt
      the extended conformation observed in all PDZ-ligand complexes when it moves away
      from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane
      penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into
      the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD
      simulations of the full D2R-GIPC1-PDZ complex in sphingolipid/cholesterol
      membranes show that the D2R carboxyl C-terminus samples the region of the
      conserved GFGL motif located on the carboxylate-binding loop of the GIPC1-PDZ,
      and the entire complex distances itself from the membrane interface. Together,
      these results outline a likely mechanism of Hx8 involvement in the interaction of
      the GPCR with PDZ-domains in the course of signaling. 

PMID- 25592840
TI  - A novel IgM-H-ficolin complement pathway to attack allogenic cancer cells in
      vitro.
AB  - The pentameric serum IgMs are critical to immune defense and surveillance through
      cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of
      oligomeric lectins with an overall structure similar to C1q and mannose-binding
      lectin (MBL) participate in microbe infection and apoptotic cell clearance by
      activating the complement lectin pathway or a primitive opsonophagocytosis. It
      remains unknown whether serum IgMs interplay with ficolins in cancer
      immunosurveillance. Here we report a natural cancer killing of different types of
      cancer cells by sera from a healthy human population mediated by a novel IgM-H
      ficolin complement activation pathway. We demonstrate for the first time that H
      ficolin bound to a subset of IgMs in positive human sera and IgM-H-ficolin
      deposited on cancer cells to activate complement attack in cancer cells. Our data
      suggest that the IgM-H-ficolin -mediated complement activation pathway may be
      another defensive strategy for human cancer immunosurveillance. 

PMID- 25592841
TI  - Synthesis of chitosan-g-poly(acrylamide)/ZnS nanocomposite for controlled drug
      delivery and antimicrobial activity.
AB  - Nanocomposite materials are gaining grounds in the fields of medicine,
      environmental sciences and for basic studies. Herein, we have developed, a novel
      method for the preparation of chitosan-g-poly(acrylamide)/ZnS (abbreviated as
      CPAZ) nanocomposite using microwave radiations. The synthesized CPAZ
      nanocomposites were characterized by Fourier transform infrared spectroscopy
      (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM) and thermo
      gravimetric analysis (TGA). FTIR results established the grafting of acrylamide
      onto chitosan backbone. TEM analysis revealed the size of the CPAZ nanocomposite
      particles in the range of 19-26 nm. XRD technique predicated the crystalline
      behavior of the nanocomposite. Therefore, XRD, TEM and FTIR spectrum analysis
      confirmed the formation of CPAZ nanocomposites. Zeta potential for CPAZ
      nanocomposite was found to be +28.2 mV which indicated its stability. The CPAZ
      nanocomposites were investigated for drug release behavior and we found a maximum
      of 79% drug release at pH 2.2. Moreover, CPAZ nanocomposite was also found to be
      antimicrobial against Escherichia coli bacteria.

PMID- 25592842
TI  - Production of exopolysaccharide from rhizobia with potential biotechnological and
      bioremediation applications.
AB  - The potential use of rhizobia under controlled fermentation conditions may result
      in the production of new extracellular polymeric substances (EPS) having novel
      and superior properties that will open up new areas of industrial applications
      and thus increase their demand. The production of EPS and the stability of
      emulsions formed with soybean oil, diesel oil and toluene using different
      concentrations of purified EPS derived from wild-type and mutant strains of
      Rhizobium tropici SEMIA 4077 was investigated. The EPS was defined as a
      heteropolysaccharide composed of six constituent monosaccharides that displayed
      higher intrinsic viscosity and pseudoplastic non-Newtonian fluid behavior in an
      aqueous solution. The ratio between the total EPS production and the cellular
      biomass was 76.70 for the 4077::Z04 mutant strain and only 8.10 for the wild-type
      strain. The EPS produced by the wild-type R. tropici SEMIA 4077 resulted in more
      stable emulsions with the tested toluene than xanthan gum, and the emulsification
      indexes with hydrocarbons and soybean oil were higher than 50%, indicating strong
      emulsion-stabilizing capacity. These results demonstrate that the EPS of R.
      tropici strains could be attractive for use in industrial and environmental
      applications, as it had higher intrinsic viscosity and good emulsification
      activity. 

PMID- 25592843
TI  - Synthesis and preservative application of quaternized carboxymethyl chitosan
      containing guanidine groups.
AB  - A chitosan derivative, quaternized carboxymethyl chitosan containing guanidine
      groups (QGCMC), was synthesized and structurally characterized using FT-IR, (1)H
      NMR spectroscopy. The elemental composition of QGCMC was also investigated.
      Increase in the molar ratio of materials used for QGCMC synthesis and an increase
      in the reaction time of QGCMC synthesis led to an increased degree of
      substitution. QGCMC demonstrated a strong antimicrobial activity at acidic,
      neutral, and basic pH conditions and could significantly lengthen the shelf life
      of strawberries. 

PMID- 25592844
TI  - Synthesis and characterization of uranyl ion-imprinted microspheres based on
      amidoximated modified alginate.
AB  - Surface ion-imprinting technique was utilized for the preparation of surface ion
      imprinted chelating microspheres based on amidoximated modified alginate (U-AOX)
      in presence of uranyl ions as a template and glutaraldehyde cross-linker.
      Different instrumental techniques such as elemental analysis, scanning electron
      microscope (SEM), FTIR, X-ray photoelectron spectroscopy (XPS) and X-ray
      diffraction spectra were employed for full investigation of the manufactured
      materials. The synthesized microspheres displayed a higher ability for selective
      extraction of UO2(2+) when compared to the non-imprinted microspheres (NI-AOX).
      In addition, the essential parameters such as pH, temperature, time and initial
      uranyl ion concentration were evaluated in order to optimize the conditions of
      the adsorption process. The results indicated that pH 5 was the best for the
      UO2(2+) removal, also, the adsorption was endothermic in nature, follows the
      second-order kinetics and the adsorption isotherm showed the best fit with
      Langmuir model with maximum adsorption capacity of 155 +/- 1 and 64 +/- 1 mg/g
      for both U-AOX and NI-AOX respectively. Desorption and regeneration had been
      carried out using 0.5M HNO3 solution and the results indicated that the
      microspheres maintained about 96% of its original efficiency after five
      consecutive adsorption-desorption cycles.

PMID- 25592845
TI  - Snoring and mortality in patients with heart failure and dialysis.

PMID- 25592847
TI  - Semi-supervised adaptive-height snipping of the hierarchical clustering tree.
AB  - BACKGROUND: In genomics, hierarchical clustering (HC) is a popular method for
      grouping similar samples based on a distance measure. HC algorithms do not
      actually create clusters, but compute a hierarchical representation of the data
      set. Usually, a fixed height on the HC tree is used, and each contiguous branch
      of samples below that height is considered a separate cluster. Due to the fixed
      height cutting, those clusters may not unravel significant functional coherence
      hidden deeper in the tree. Besides that, most existing approaches do not make use
      of available clinical information to guide cluster extraction from the HC. Thus,
      the identified subgroups may be difficult to interpret in relation to that
      information. RESULTS: We develop a novel framework for decomposing the HC tree
      into clusters by semi-supervised piecewise snipping. The framework, called guided
      piecewise snipping, utilizes both molecular data and clinical information to
      decompose the HC tree into clusters. It cuts the given HC tree at variable
      heights to find a partition (a set of non-overlapping clusters) which does not
      only represent a structure deemed to underlie the data from which HC tree is
      derived, but is also maximally consistent with the supplied clinical data.
      Moreover, the approach does not require the user to specify the number of
      clusters prior to the analysis. Extensive results on simulated and multiple
      medical data sets show that our approach consistently produces more meaningful
      clusters than the standard fixed-height cut and/or non-guided approaches.
      CONCLUSIONS: The guided piecewise snipping approach features several novelties
      and advantages over existing approaches. The proposed algorithm is generic, and
      can be combined with other algorithms that operate on detected clusters. This
      approach represents an advancement in several regards: (1) a piecewise tree
      snipping framework that efficiently extracts clusters by snipping the HC tree
      possibly at variable heights while preserving the HC tree structure; (2) a
      flexible implementation allowing a variety of data types for both building and
      snipping the HC tree, including patient follow-up data like survival as auxiliary
      information. The data sets and R code are provided as supplementary files. The
      proposed method is available from Bioconductor as the R-package HCsnip.

PMID- 25592848
TI  - Differential expression of fertility genes boule and dazl in Chinese sturgeon
      (Acipenser sinensis), a basal fish.
AB  - The gene family DAZ (deleted in Azoospermia), including boule, dazl and DAZ,
      performs highly conserved functions in germ cell development and fertility across
      animal phyla. Differential expression patterns have been demonstrated for the
      family members in invertebrates and vertebrates including fish. Here, we report
      the identification of boule and dazl and their expression at both RNA and protein
      levels in developing and mature gonads of Chinese sturgeon (Acipenser sinensis).
      Firstly, the isolation of the boule and dazl genes in Chinese sturgeon and the
      observation of the two genes in coelacanth suggest that dazl originated after the
      divergence of bony fish from cartilaginous fish but before the emergence of the
      Actinistia. Quantitative real-time PCR and western blot analyses reveal that
      boule and dazl RNA and proteins are restricted to the testis and ovary. In situ
      hybridization and fluorescent immunohistochemistry show that the bisexual mitotic
      and meiotic germ cell expression of dazl RNA and protein is conserved in
      vertebrates, while Chinese sturgeon boule RNA and protein exhibit mitotic and
      meiotic expression in the testis, and also likely display mitotic and meiotic
      expression in female. Moreover, we directly demonstrate for the first time that
      sturgeon Balbiani body/mitochondrial cloud disperses in the cytoplasm of early
      developing oocytes and co-localizes with Dazl to some extent. Finally,
      urbilaterian boule may also have an ancestral function in oogenesis. Taken
      together, these results provide useful information on the evolution of DAZ family
      genes, expression patterns and functions in animal reproduction.

PMID- 25592849
TI  - Multielement stoichiometry in Quercus variabilis under natural phosphorus
      variation in subtropical China.
AB  - Plant stoichiometry in relation to environmental factors has recently received
      increasing attention. However, regulations and variations of plant elements in
      different environments are not well understood. We investigated homeostasis and
      variation of macroelements (C, N, P, K, Ca, Mg, and S), essential microelements
      (Fe, Mn, and Zn) and non-essential elements (Al) in Quercus variabilis leaves at
      a range of natural P concentration from P-rich to P-deficient (typical
      subtropical conditions) soils. The results showed that element ratios were more
      stable (except for C:P and Mn:P) than individual element concentrations. Of the
      individual elements, protein-related elements (e.g. N, S, and Fe) were correlated
      with leaf P while non-protein elements (e.g. C, K, and Ca) were not. The degree
      of homeostasis indicated that macroelements (N, P, and Ca) concentrations were
      more variable than microelements (Mn, Zn, and Al) under a varying element
      concentration in soils. These results suggest that local P-rich geochemistry
      alters leaf element concentrations, but not element ratios, and that plants are
      capable of meeting their needs for elements in certain proportions to achieve
      optimal performance under varying elemental conditions. 

PMID- 25592850
TI  - The fire within psoriatic patients: overlap between inflammatory and
      cardiovascular diseases.

PMID- 25592851
TI  - Serial Takotsubo syndrome and its implications.

PMID- 25592846
TI  - Ebola: translational science considerations.
AB  - We are currently in the midst of the most aggressive and fulminating outbreak of
      Ebola-related disease, commonly referred to as "Ebola", ever recorded. In less
      than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over
      10,000 people, indiscriminately of gender or age, with a fatality rate of about
      50%. Whereas at its onset this Ebola outbreak was limited to three countries in
      West Africa (Guinea, where it was first reported in late March 2014, Liberia,
      where it has been most rampant in its capital city, Monrovia and other
      metropolitan cities, and Sierra Leone), cases were later reported in Nigeria,
      Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US
      (i.e., Dallas, Texas; New York City) by late October 2014. World and US health
      agencies declared that the current Ebola virus disease (EVD) outbreak has a
      strong likelihood of growing exponentially across the world before an effective
      vaccine, treatment or cure can be developed, tested, validated and distributed
      widely. In the meantime, the spread of the disease may rapidly evolve from an
      epidemics to a full-blown pandemic. The scientific and healthcare communities
      actively research and define an emerging kaleidoscope of knowledge about critical
      translational research parameters, including the virology of EBOV, the molecular
      biomarkers of the pathological manifestations of EVD, putative central nervous
      system involvement in EVD, and the cellular immune surveillance to EBOV, patient
      centered anthropological and societal parameters of EVD, as well as translational
      effectiveness about novel putative patient-targeted vaccine and pharmaceutical
      interventions, which hold strong promise, if not hope, to curb this and future
      Ebola outbreaks. This work reviews and discusses the principal known facts about
      EBOV and EVD, and certain among the most interesting ongoing or future avenues of
      research in the field, including vaccination programs for the wild animal vectors
      of the virus and the disease from global translational science perspective. 

PMID- 25592852
TI  - In response to Canto et al.--Time to standardize and broaden the criteria of
      acute coronary syndrome symptom presentations in women.

PMID- 25592853
TI  - Safety of urgent cardioversion for patients with recent-onset atrial fibrillation
      and flutter.

PMID- 25592854
TI  - Neutrophil/lymphocyte ratio and the oxidative stress burden.

PMID- 25592856
TI  - Evolution of the Serbian pharmaceutical market alongside socioeconomic
      transition.
AB  - INTRODUCTION: South-eastern European socioeconomic transition followed by
      extensive health systems reforms has completely changed the pharmaceuticals
      market landscape in the region. Serbia, as the largest Western Balkans market,
      may serve as an example of such changes. METHODS: Descriptive trend analysis of
      national-level dispensing of medicines in Serbia 2004-2012 was performed.
      RESULTS: Total public health expenditure in Serbia increased sharply in less than
      a decade (?1,175,158,679 to ?1,847,971,776); public spending on pharmaceuticals
      doubled (?339,279,304 to ?742,013,976). Market growth was primarily driven by
      statins, novel platelet aggregation inhibitors, monoclonal antibodies and
      combined preparations indicated in asthma and chronic obstructive pulmonary
      disease. CONCLUSION: The pharmaceutical market of Serbia has undergone thorough
      and complete transformation from within. Serious crisis of medicine supply
      sustainability is currently shaking Balkan health systems due to increasing
      public debt worsened by global recession. More responsible reimbursement policy
      rooted in cost-effectiveness principle is needed in years to come.

PMID- 25592855
TI  - Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter,
      Open-Label, Noninferiority, Randomized Controlled Trial.
AB  - Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from
      steroids or steroid-sparing agents. This open-label, noninferiority, randomized
      controlled trial at four sites in Italy tested whether rituximab is noninferior
      to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1
      16 years who had developed SDNS in the previous 6-12 months and were maintained
      in remission with high prednisone doses (>=0.7 mg/kg per day). We randomly
      assigned participants to continue prednisone alone for 1 month (control) or to
      add a single intravenous infusion of rituximab (375 mg/m(2); intervention).
      Prednisone was tapered in both groups after 1 month. For noninferiority,
      rituximab had to permit steroid withdrawal and maintain 3-month proteinuria
      (mg/m(2) per day) within a prespecified noninferiority margin of three times the
      levels among controls (primary outcome). We followed participants for >=1 year to
      compare risk of relapse (secondary outcome). Fifteen children per group (21 boys;
      mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for <=60
      months (median, 22 months). Three-month proteinuria was 42% lower in the
      rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to
      1.95 [i.e., within the noninferiority margin of three times the levels in
      controls]). All but one child in the control group relapsed within 6 months;
      median time to relapse in the rituximab group was 18 months (95% confidence
      interval, 9 to 32 months). In the rituximab group, nausea and skin rash during
      infusion were common; transient acute arthritis occurred in one child. In
      conclusion, rituximab was noninferior to steroids for the treatment of juvenile
      SDNS. 

PMID- 25592857
TI  - Molecular identification of non-tuberculous mycobacteria isolated from clinical
      specimens in Zambia.
AB  - BACKGROUND: The emergence of Acquired Immunodeficiency Syndrome has highlighted
      the increased incidence and importance of the disease caused by Non-tuberculous
      Mycobacteria (NTM). While disease due to M. avium-intracellulare complex is
      apparently common throughout the world, other Non-tuberculous mycobacterial
      species have been isolated from both immunocompromised and immunocompetent
      individuals. The increasing number of infections caused by these organisms has
      made it clinically important to quickly identify mycobacterial species. The
      diagnosis of a pathogenic versus a non-pathogenic species not only has
      epidemiological implications but is also relevant to the demands of patient
      management. Since antibiotic treatment varies according to the species
      encountered, species identification would reduce the burden of some of these
      emerging opportunistic pathogens especially in immunocompromised patients and
      improve their quality of life. FINDINGS: A total of 91 NTM suspected isolates
      from four regions of Zambia were included in the study. These isolates were
      identified using the sequence analysis of the 16S-23S rRNA intergenic transcribed
      spacer (ITS) region of Mycobacteria. Fifty-four of the 91 (59%) isolates were
      identified as NTM and these included M. intracellulare (27.8%), M. lentiflavum
      (16.7%), M. avium (14.8%), M. fortuitum (7.4%), M. gordonae (7.4%), M.
      kumamotonense (3.7%), M. indicus pranii (3.7%), M. peregrinum (3.7%), M.
      elephantis (1.85%), M. flavescens (1.85%), M. asiaticum (1.85%), M.
      bouchedurhonense (1.85%), M. chimaera (1.85%), M. europaeum (1.85%), M. neourum
      (1.85%), M. nonchromogenicum (1.5%). CONCLUSION: The study has shown that DNA
      sequencing of the ITS region may be useful in the preliminary identification of
      NTM species. All species identified in this study were potentially pathogenic.

PMID- 25592858
TI  - Role of Interferon-lambda in Allergic Asthma.
AB  - Type III interferons (IFNs), or IFN-lambda, are known to have potent antiviral
      and antiproliferative activities. It inhibits viral replication and upregulates
      cytotoxic responses to virally infected cells. Besides these characteristics, IFN
      lambda also has additional activities in the immune system. In fact, it induces
      the proliferation of Foxp3-expressing regulatory T cells mediated in part by
      dendritic cells and inhibit the production of IL-5 and IL-13 in vitro. Regulatory
      T cells and the Th2 cytokines like IL-5 and IL-13 play important roles in the
      pathogenesis of allergic asthma. In humans, there seems to be an inverse link
      between IFN-lambda and the severity of allergic asthma and allergic asthma
      exacerbations. Asthmatic patients, without a detectable viral infection show an
      inverse correlation between IL-28 and IL-29 mRNA levels and severity of allergic
      responses in the airways. These additional features of IFN-lambda that affect the
      adaptive immune system make it a potential immunotherapeutic agent for the
      treatment of allergic asthma.

PMID- 25592859
TI  - Reproductive biology of largescale tonguesole Cynoglossus arel in coastal waters
      of Bandar Abbas, Persian Gulf, Iran.
AB  - The objectives of this study were to determine the reproductive cycle of
      largescale tonguesole Cynoglossus arel, a commercially valuable flatfish species,
      in coastal waters of Bandar Abbas, along the south coast of Iran in the Persian
      Gulf. From October 2009 to September 2010, 905 fish were collected in monthly
      samples, and their length, weight, sex, gonad weight, and maturity status
      recorded. These data revealed that ovary weight in females is low from July to
      September, then increases to a peak in February followed by a decrease,
      indicating that the peak spawning season is from February to March with some
      spawning lasting until June. Males showed a corresponding seasonal pattern in
      testis weight, although with much less pronounced seasonal differences than gonad
      weight in females. Five maturity classes were described based on ovarian and
      testicular histology, corresponding with macroscopic analysis of gonads. The
      spawning season in C. arel is prolonged, similar to several other tropical
      flatfish species, and larger adult females tended to have an even more prolonged
      spawning period than smaller, presumably younger adult females. Combined, our
      results indicated that C. arel is a winter-to-spring batch spawner with an
      asynchronous type of ovarian development.

PMID- 25592860
TI  - Effect of magnetized extender on sperm membrane integrity and development of
      oocytes in vitro fertilized with liquid storage boar semen.
AB  - The objective of this study was to evaluate the effect of a magnetized extender
      on sperm membrane damage and development of oocytes in vitro fertilized with
      liquid storage boar semen. Before semen dilution, extender was flowed through a
      neodymium magnet (0, 2000, 4000 and 6000G) for 5min and collected semen was
      preserved for 168h at 18 degrees C. In results, plasma membrane integrity with
      live sperm was significantly higher in semen treated with extenders magnetized at
      4000G than sperm treated with extenders magnetized at 0G during semen
      preservation for 120-168h (p<0.05). In addition, acrosomal membrane damage was
      significantly lower in semen treated with extenders magnetized at 4000 and 6000G
      compared to 0 and 2000G during semen preservation for 168h (p<0.05). And
      mitochondrial membrane damage with all sperm was significantly lower in semen
      treated with extenders magnetized at 2000G than other groups during semen
      preservation for 168h. The ability of semen to achieve successful in vitro
      fertilization was also not significantly different among the groups during
      preservation. However, when the semen was preserved for 168h, the blastocyst
      formation rates were significantly higher at 6000G compared to 0 and 2000G
      (p<0.05). In conclusion, these results suggest that highly magnetized semen
      extender could protect the sperm membrane from damage, and improve the ability of
      rates of in vitro blastocyst development and magnetized semen diluter is
      beneficial for long liquid preservation of boar semen. 

PMID- 25592861
TI  - Biochemical composition and protein profile of alpaca (Vicugna pacos) oviductal
      fluid.
AB  - Knowledge and assessment of the constituents of the oviductal fluid (OF) in
      camelids is necessary for a correct formulation of specific culture media for the
      development of reproductive biotechnology. This study is the first describing the
      biochemical composition and SDS-PAGE protein profile of alpaca oviductal fluid in
      non-pregnant animals and animals that have completed the first month and second
      month of gestation. Samples were also classified into oviducts that were
      ipsilateral or contralateral to the ovary with corpus luteum. No differences were
      found between both oviducts, whereas pregnant and non-pregnant females displayed
      significant differences in the biochemical composition and protein profile of the
      oviductal fluid. Relative albumin content was higher in non-pregnant females.
      Relative creatinine content in OF from females that have completed the second
      month of gestation was lower than non-pregnant females and females that have
      completed the first month of gestation. Ion Na(+) concentration was higher in OF
      from non-pregnant females when compared with pregnant ones. The protein profile
      of non-pregnant females showed five protein bands of 70, 42, 25, 24 and 19kDa
      that were significantly more intense compared with pregnant animals. Bands were
      identified as moesin, actin cytoplasmic 2, hydroxypyruvate isomerase, ferritin
      light chain and peroxiredoxin-6 with MALDI/MS. Our results encourage more
      thorough future studies, in order to unravel the complex reproductive processes
      of the South American camelid oviduct. 

PMID- 25592862
TI  - Characterization of neuronal death and functional deficits following nerve injury
      during the early postnatal developmental period in rats.
AB  - In contrast to adult rat nerve injury models, neonatal sciatic nerve crush leads
      to massive motor and sensory neuron death. Death of these neurons results from
      both the loss of functional contact between the nerve terminals and their
      targets, and the inability of immature Schwann cells in the distal stump of the
      injured nerve to sustain regeneration. However, current dogma holds that little
      to no motoneuron death occurs in response to nerve crush at postnatal day 5 (P5).
      The purpose of the current study was to fully characterize the extent of motor
      and sensory neuronal death and functional recovery following sciatic nerve crush
      at mid-thigh level in rats at postnatal days 3-30 (P3-P30), and then compare this
      to adult injured animals. Following nerve crush at P3, motoneuron numbers were
      reduced to 35% of that of naive uninjured animals. Animals in the P5 and P7 group
      also displayed statistically fewer motoneurons than naive animals. Animals that
      were injured at P30 or earlier displayed statistically lower sensory neuron
      counts in the dorsal root ganglion than naive controls. Surprisingly, complete
      behavioral recovery was observed exclusively in the P30 and adult injured groups.
      Similar results were observed in muscle twitch/tetanic force analysis, motor unit
      number estimation and wet muscle weights. Rats in both the P5 and P7 injury
      groups displayed significant neuronal death and impaired functional recovery
      following injury, challenging current dogma and suggesting that severe deficits
      persist following nerve injury during this early postnatal developmental period.
      These findings have important implications concerning the timing of neonatal
      nerve injury in rats.

PMID- 25592863
TI  - Investigation of the prenatal expression patterns of 108 schizophrenia-associated
      genetic loci.

PMID- 25592864
TI  - Seroprevalence of human Toxocara infections in the Roma and non-Roma populations
      of Eastern Slovakia: a cross-sectional study.
AB  - Socioeconomic conditions and health of the Roma population, the most numerous
      minority in Europe, are worse than that of the non-Roma population. Information
      about the occurrence of human toxocarosis and other parasitic diseases in the
      Roma population is scarce or completely missing. The aim of this study was to map
      the seroprevalence of toxocarosis in the population living in segregated Roma
      settlements and to compare the data with the occurrence of antibodies in the non
      Roma population of Eastern Slovakia. The seropositivity to Toxocara in 429
      examined Roma inhabitants of segregated settlements reached 22.1%, while only
      4/394 samples of the non-Roma population were found to be positive (odds ratio
      27.7, P < 0.0001). Headache, muscle pain, influenza-like symptoms and diarrhoea
      occurred significantly more often in seropositive persons than in seronegative
      individuals. In the Roma population positivity was not influenced by gender,
      level of education and poverty, but age, lack of sanitary facilities and heating
      with wood significantly increased the risk of infection. It can be assumed that
      besides the high prevalence of toxocarosis, other parasitic diseases and
      communicable diseases will also be more prevalent in the Roma population living
      in segregated settlements. 

PMID- 25592865
TI  - LGR5 expression in oral epithelial dysplasia and oral squamous cell carcinoma.
AB  - OBJECTIVE: LGR5 is pivotal to oral cavity development and is implicated in
      epithelial malignancy whereby stimulation of LGR5 potentiates canonical Wnt
      signaling. This investigation tested our hypothesis of a correlation between LGR5
      expression and the severity of oral epithelial dysplasia (OED) and oral squamous
      cell carcinoma (OSCC). STUDY DESIGN: Immunoreactive LGR5 protein expression was
      quantified in 342 tissue samples ranging in disease severity from normal through
      mild and moderate or severe OED to OSCC. RESULTS: LGR5 was restricted to the
      basal layers for normal tissues, projected to the stratum granulosum in severe
      dysplasia, intense in carcinoma nests of well-differentiated OSCC, but uniformly
      diffuse throughout poorly differentiated OSCC. Median LGR5 immunoreactivity index
      scores increased with disease severity: mild dysplasia = 1 < moderate or severe
      dysplasia = 2.5 < OSCC = 6. CONCLUSIONS: Inclusion of LGR5 in a panel of
      immunohistochemical biomarkers may improve identification of increased potential
      for malignancy in OED.

PMID- 25592866
TI  - Relationship between physical factors and subjective image quality of cone-beam
      computed tomography images according to diagnostic task.
AB  - OBJECTIVE: This study was designed to investigate the relationship between
      physical factors and the subjective quality of cone beam computed tomography
      (CBCT) images used for different diagnostic tasks. STUDY DESIGN: CBCT images of a
      real skull phantom and a SedentexCT IQ phantom were acquired under different
      exposure conditions (one Dinnova3 CBCT scanner, 60-110 kV and 4-10 mA).
      Radiologists evaluated subjective image quality of real skull phantom images for
      each diagnostic task. On the basis of the evaluation results, the images were
      classified into two groups: acceptable and unacceptable. The modulation transfer
      function (MTF), contrast-to-noise ratio (CNR), and image uniformity were measured
      using the SedentexCT IQ phantom images. The differences in physical factors were
      evaluated. RESULTS: MTF and CNR values showed statistical differences in image
      quality in two groups with regard to all diagnostic tasks. In the maxilla, MTF
      and CNR values showed no significant differences between periapical diagnosis and
      implant planning in the acceptable groups. Higher MTF and CNR values were
      required in the periapical diagnosis compared with the implant planning of the
      mandible. CONCLUSIONS: This study proved that MTF and CNR values have a
      significant association with subjective image quality. The diagnostic task should
      be considered in evaluation of CBCT image quality.

PMID- 25592867
TI  - Assessment of morbidity following insertion of fixed preoperative orthopedic
      appliance in infants with complete cleft lip and palate.
AB  - OBJECTIVE: To examine physiologic and behavioral indicators of pain within the
      first 24 hours following insertion of the fixed presurgical orthopedic appliance
      (FPOA) under general anesthesia in infants with unilateral and bilateral complete
      cleft lip and palate. METHODS: The study sample included 109 infants who had
      either a dentomaxillary appliance (DMA) or an elastomeric chain premaxillary
      retraction (ECPR) appliance. Vital signs and FLACC (Face, Legs, Activity, Cry,
      Consolability) scores were used to measure the outcomes. RESULTS: There was an
      initial postoperative increase in the median heart rate. Heart rate returned to
      the median baseline level by 8 hours. The median systolic blood pressure
      increased postoperatively and remained elevated throughout the time of
      evaluation. The median respiratory rate remained below that at baseline
      throughout the study period. The highest mean change in FLACC measurements was
      observed approximately 2 hours postoperatively. By 3 hours postoperatively, the
      scores decreased. CONCLUSIONS: Although there was a large individual variability,
      the FLACC scores became reduced after 3 hours following surgical insertion of the
      DMA and the ECPR appliance.

PMID- 25592868
TI  - Pharyngeal airway morphology in healthy individuals and in obstructive sleep
      apnea patients treated with maxillomandibular advancement: a comparative study.
AB  - OBJECTIVE: This study investigated the differences in airway morphology between
      control patients and those with obstructive sleep apnea (OSA) treated with
      maxillomandibular advancement (MMA) to gain better insight into the beneficial
      effects of MMA on airway morphology and OSA severity. STUDY DESIGN: This
      retrospective case-control study included preoperative radiographic data gathered
      for all patients; postoperative radiographic data were gathered for the OSA
      group. Statistical analysis, including the Student t test, and simple linear
      regression was performed to identify differences in cephalometric and airway
      variables among the three groups and to associate airway morphology to disease
      severity. RESULTS: Twenty-four patients (12 with OSA; 12 controls) treated at the
      same clinic were included in this study. Statistically significant differences
      versus control values were found for preoperative total airway volume,
      postoperative airway length, and both pre- and postoperative airway minimum cross
      sectional areas. In general, the untreated OSA airway was anatomically
      compromised in comparison with controls, whereas the treated airway showed
      significant morphologic improvements, comparable with the control group values.
      CONCLUSIONS: MMA produces statistically significant airway improvements for OSA
      patients, producing airway morphology comparable with that of the controls.
      However, some degree of residual OSA may still exist. Therefore, factors other
      than static airway morphology contribute to OSA pathogenesis.

PMID- 25592869
TI  - CIP-36, a novel topoisomerase II-targeting agent, induces the apoptosis of
      multidrug-resistant cancer cells in vitro.
AB  - The need to overcome cancer multidrug resistance (MDR) has fueled considerable
      interest in the development of novel synthetic antitumor agents with cytotoxicity
      against cancer cell lines with MDR. In this study, we aimed to investigate CIP
      36, a novel podophyllotoxin derivative, for its inhibitory effects on human
      cancer cells from multiple sources, particularly cells with MDR in vitro. The
      human leukemia cell line, K562, and the adriamycin-resistant subline, K562/A02,
      were exposed to CIP-36 or anticancer agents, and various morphological and
      biochemical properties were assessed by Hoechst 33342 staining under a
      fluorescence microscope. Subsequently, cytotoxicity, cell growth curves and the
      cell cycle were analyzed. Finally, the effects of CIP-36 on topoisomerase IIalpha
      (Topo IIalpha) activity were determined. Treatment with CIP-36 significantly
      inhibited the growth of the K562 and MDR K562/A02 cells. Our data demonstrated
      that CIP-36 induced apoptosis, inhibited cell cycle progression and inhibited
      Topo IIalpha activity. These findings suggest that CIP-36 has the potential to
      overcome the multidrug resistance of K562/A02 cells by mediating Topo IIalpha
      activity.

PMID- 25592870
TI  - Genetic characterisation and phylogenetic analysis of PCV2 isolates from India:
      indications for emergence of natural inter-genotypic recombinants.
AB  - Porcine circovirus type 2 (PCV2), the necessary agent in pathogenesis of porcine
      circovirus diseases (PCVDs), has a worldwide distribution and is considered as
      one of the most important emerging viral pathogens of economic importance. PCV2
      has been divided into four major genotypes namely PCV2a with five clusters or
      subtypes (2A-2E), PCV2b with three clusters (1A-1C), PCV2c and PCV2d, based on
      capsid (cap) gene analysis. PCV2 genome is rapidly evolving through events of
      recombination and mutation. Though, PCV2a was the predominant genotype initially,
      PCV2b shared majority of PCV2 sequences submitted to GenBank since 2003. In
      India, data regarding molecular characterisation of PCV2 is scant or absent. In
      the present study, we thoroughly analysed genetic heterogeneity of PCV2 strains
      circulating in Indian pig population. The results revealed that pigs in this
      region harboured PCV2 viruses of different genotypes including PCV2a-2D, PCV2b-1C
      and PCV2d. More interestingly, two isolates (PCV2Izn-89-13 and PCV2Izn-218-13)
      were classified as recombinant strains. Further detailed analysis suggested that
      these strains evolved from inter-genotypic recombination between PCV2a-2C and
      PCV2b-1C genotypes within cap gene. This study reports for the first time, the
      emergence of recombinant PCV2 strains in the Indian pig population. 

PMID- 25592871
TI  - A nationwide population-based cohort study to identify the correlation between
      heart failure and the subsequent risk of herpes zoster.
AB  - BACKGROUND: The association between heart failure (HF) and herpes zoster has
      rarely been studied. We investigated the hypothesis that HF may increase the risk
      of herpes zoster in Taiwan using a nationwide Taiwanese population-based claims
      database. METHOD: Our study cohort consisted of patients who received a diagnosis
      of HF in 2001 ~ 2009 (N = 4785). For a comparison cohort, three age- and gender
      matched control patients for every patient in the study cohort were selected
      using random sampling (N = 14,355). All subjects were tracked for 1 year from the
      date of cohort entry to identify whether or not they had developed herpes zoster.
      Cox proportional-hazard regressions were performed to evaluate 1-year herpes
      zoster-free survival rates. RESULTS: The main finding of this study was that
      patients with HF seemed to be at an increased risk of developing herpes zoster.
      Of the total patients, 211 patients developed herpes zoster during the 1-year
      follow-up period, among whom 83 were HF patients and 128 were in the comparison
      cohort. The adjusted hazard ratio (AHR) of herpes zoster in patients with HF was
      higher (AHR: 2.07; 95% confidence interval (CI): 1.54 ~ 2.78; p < 0.001) than
      that of the controls during the 1-year follow-up. Our study also investigated
      whether HF is a gender-dependent risk factor for herpes zoster. We found that
      male patients with HF had an increased risk of developing herpes zoster (AHR:
      2.30 95% CI: 1.51 ~ 3.50; p < 0.001). CONCLUSIONS: The findings of our population
      based study suggest that patients with HF may have an increased risk of herpes
      zoster. These health associations should be taken into consideration, and further
      studies should focused on the cost-effectiveness of the herpes zoster vaccine
      should be designed for HF patients.

PMID- 25592872
TI  - Misregulation of polo-like protein kinase 1, P53 and P21WAF1 in epithelial
      ovarian cancer suggests poor prognosis.
AB  - Polo-like protein kinase 1 (PLK1), P53 and P21WAF1 are relevant to cell cycle
      checkpoints and cancer biology. Misregulation of PLK1, P53 and P21WAF1 has been
      detected in several types of malignant tumors. The present study aimed to clarify
      the role of PLK1, P53 and P21WAF1 in the prognosis of ovarian cancer. PLK1 and
      P53 shRNA lentiviral plasmids were transfected into SK-OV-3 cells, respectively.
      Cell proliferation, apoptosis and invasion were examined by MTT assay, flow
      cytometry and Matrigel assay, respectively. Survival time of the animals was
      observed in a xenograft model. Expression levels of PLK1, P53 and P21WAF1 were
      detected in different ovarian tissues by immunohistochemistry and western blot
      analysis. Their correlations to the clinicopathologic characteristics of the
      epithelial ovarian cancer (EOC) cases and their interrelationships were analyzed.
      Risk factors of prognosis for EOC were determined by logistic regression
      analysis. The survival time of EOC patients was measured by Kaplan-Meier
      analysis. After PLK1 or P53 knockdown, proliferation of the SK-OV-3 cells was
      inhibited, the apoptosis rate was increased, and cell invasion was suppressed in
      vitro, and the survival time was prolonged in the animals. Expression levels of
      P53, p-P53 (Ser15), P21WAF1, growth arrest and DNA damage-inducible gene 45
      (GADD45) and 14-3-3sigma were upregulated in the SK-OV-3 cells after PLK1
      knockdown, but downregulated after P53 knockdown. Higher expression levels of
      PLK1 and P53 were observed in patients with a higher FIGO stage and worse
      histological differentiation, but lower P21WAF1 was noted at a higher FIGO stage.
      Negative correlations were observed between expression of PLK1 and P53 and P53
      and P21WAF1 in the EOC cases. PLK1, P53 and P21WAF1 could be used to assess the
      prognosis of EOC, respectively, but only PLK1 was found to be an independent
      prognostic factor. The overall survival time of subjects exhibiting PLK1
      positive/P53-positive expression and PLK1-positive/P21WAF1-negative expression
      was obviously shorter than the other patient groups at the end of the follow-up.
      These results indicate that PLK1 is implicated in ovarian carcinogenesis and may
      owe its ability to inhibition of the activity of P53. In addition, misregulation
      of PLK1 coincident with P53 and P21WAF1 in EOC suggests poor prognosis.

PMID- 25592873
TI  - Hepatic and fecal metabolomic analysis of the effects of Lactobacillus rhamnosus
      GG on alcoholic fatty liver disease in mice.
AB  - The interactions among the gut, liver, and immune system play an important role
      in liver disease. Probiotics have been used for the treatment and prevention of
      many pathological conditions, including liver diseases. Comprehensive two
      dimensional gas chromatography time-of-flight mass spectrometry (GC*GC-TOF MS)
      was used herein, in conjunction with chemometric data analysis, to identify
      metabolites significantly affected by probiotics in mice fed with or without
      alcohol. The metabolomics analysis indicates that the levels of fatty acids
      increased in mouse liver and decreased in mouse feces when mice were chronically
      exposed to alcohol. Supplementing the alcohol-fed mice with culture supernatant
      from Lactobacillus rhamnosus GG (LGGs) normalized these alcohol-induced
      abnormalities and prevented alcoholic liver disease (ALD). These results agree
      well with previous studies. In addition to diet-derived long chain fatty acids
      (LCFAs), LGGs may positively modify the gut's bacterial population to stimulate
      LCFA synthesis, which has been shown to enhance intestinal barrier function,
      reduce endotoxemia, and prevent ALD. We also found that several amino acids,
      including l-isoleucine, a branched chain amino acid, were downregulated in the
      liver and fecal samples from animals exposed to alcohol and that the levels of
      these amino acids were corrected by LGGs. These results demonstrate that LGGs
      alleviates alcohol-induced fatty liver by mechanisms involving increasing
      intestinal and decreasing hepatic fatty acids and increasing amino acid
      concentration. 

PMID- 25592874
TI  - Spatial distribution of selected persistent organic pollutants (POPs) in
      Australia's atmosphere.
AB  - A nation-wide passive air sampling campaign recorded concentrations of persistent
      organic pollutants in Australia's atmosphere in 2012. XAD-based passive air
      samplers were deployed for one year at 15 sampling sites located in
      remote/background, agricultural and semi-urban and urban areas across the
      continent. Concentrations of 47 polychlorinated biphenyls ranged from 0.73 to 72
      pg m(-3) (median of 8.9 pg m(-3)) and were consistently higher at urban sites.
      The toxic equivalent concentration for the sum of 12 dioxin-like PCBs was low,
      ranging from below detection limits to 0.24 fg m(-3) (median of 0.0086 fg m(-3)).
      Overall, the levels of polychlorinated biphenyls in Australia were among the
      lowest reported globally to date. Among the organochlorine pesticides,
      hexachlorobenzene had the highest (median of 41 pg m(-3)) and most uniform
      concentration (with a ratio between highest and lowest value ~5). Bushfires may
      be responsible for atmospheric hexachlorobenzene levels in Australia that
      exceeded Southern Hemispheric baseline levels by a factor of ~4. Organochlorine
      pesticide concentrations generally increased from remote/background and
      agricultural sites to urban sites, except for high concentrations of alpha
      endosulfan and DDTs at specific agricultural sites. Concentrations of heptachlor
      (0.47-210 pg m(-3)), dieldrin (ND-160 pg m(-3)) and trans- and cis-chlordanes
      (0.83-180 pg m(-3), sum of) in Australian air were among the highest reported
      globally to date, whereas those of DDT and its metabolites (ND-160 pg m(-3), sum
      of), alpha-, beta-, gamma- and delta-hexachlorocyclohexane (ND-6.7 pg m(-3), sum
      of) and alpha-endosulfan (ND-27 pg m(-3)) were among the lowest. 

PMID- 25592875
TI  - Dual ameliorative effects of Ningdong granule on dopamine in rat models of
      Tourette's syndrome.
AB  - Dopamine (DA) is a key neuromodulator in the brain that supports motor and
      cognitive functions. Here, we use apomorphine (Apo) and 3,3'-iminodipropionitrile
      (IDPN) to develop two rat models of Tourette's syndrome (TS), a common
      neuropsychiatric disorder characterized by stereotyped repetitive involuntary
      tics. The models enabled the assessment of unique ameliorative effects of
      Ningdong granule (NDG), a traditional Chinese medicine (TCM) preparation
      dedicated to the treatment of TS, on the striatal DA content of rats. By using
      high-performance liquid chromatography (HPLC), we found that long-term
      administration of NDG could, at least partially, restore the striatal dopamine
      alterations, either by increasing them after IDPN treatment or by decreasing them
      after Apo treatment. Taken together, our data indicated that NDG could ameliorate
      the abnormal striatal DA content dually, and the unique therapeutic property may
      be meaningful for the treatment of TS. 

PMID- 25592876
TI  - Molecular cloning, characterization and expression analysis of PPAR gamma in the
      orange-spotted grouper (Epinephelus coioides) after the Vibrio alginolyticus
      challenge.
AB  - PPAR gamma was a key nuclear receptor, playing an important role in the immune
      defense and the anti-inflammatory mechanism. In this study, the full-length PPAR
      gamma (EcPPAR gamma) was obtained, containing a 5'UTR of 133 bp, an ORF of 1602
      bp and a 3'UTR of 26 bp besides the poly (A) tail. The EcPPAR gamma gene encoded
      a protein of 533 amino acids with an estimated molecular mass of 60.02 KDa and a
      predicted isoelectric point (pI) of 6.26. The deduced amino acid sequence showed
      that EcPPAR gamma consisted of the conserved residues and the domains known to be
      critical for the PPAR gamma function. The quantitative real-time PCR analysis
      revealed that EcPPAR gamma transcript was expressed in all the examined tissue,
      while the strong expression was observed in intestine, followed by the expression
      in liver, gill, spleen heart, kidney and muscle. Vibrio challenge could stimulate
      the inflammatory response in grouper and induce a sharp increase of pro
      inflammatory cytokines expression, lipid peroxidation and DNA damage, while the
      up-regulation of vibrio-induced inflammation could also increase the non-specific
      immune defense. The groupers challenged with Vibrio alginolyticus showed a sharp
      increase of EcPPAR gamma transcript in immune tissues. Subcellular localization
      analysis revealed that EcPPAR gamma was distributed in the nucleus. Furthermore,
      overexpression of EcPPAR gamma could down-regulated the expression of IL1b, IL6,
      TNF1 and TNF2. In addition, the administration of PPAR gamma antagonist, GW9662,
      could up-regulate the expression of pro-inflammatory genes, including IL1b, IL6,
      TNF1 and TNF2. Together, these results indicated that EcPPAR gamma serving as a
      negative regulator of pro-inflammatory cytokines may play an important role in
      the immune defense against vibrio-induced inflammation in grouper. 

PMID- 25592877
TI  - Identification, tissue distribution and characterization of two heat shock
      factors (HSFs) in goldfish (Carassius auratus).
AB  - Heat shock proteins (HSPs) are synthesized rapidly in response to a variety of
      physiological or environmental stressors, whereas the transcriptional activation
      of HSPs is regulated by a family of heat shock factors (HSFs). In vertebrates,
      multiple HSFs (HSF1-4) have been reported to have different roles in response to
      a range of stresses. This paper reports the cDNA cloning of two goldfish
      (Carassius auratus) HSF gene families, HSF1 and three isoforms of HSF2. Both HSF1
      and HSF2s showed high homology to the known HSFs from other organisms,
      particularly the zebrafish. Different patterns of HSF1 and HSF2 mRNA expression
      were detected in several goldfish tissues, highlighting their distinct roles. In
      cadmium (Cd)-treated tissues, the responses of HSP70 showed less difference.
      However, the increase in HSF1 and HSF2 in these tissues differs considerable. In
      particular, HSF2 was induced strongly in the heart and liver. On the other hand,
      in heart tissue, HSF1 showed the smallest increment. These results suggest the
      potential role of HSF2 in assisting HSF1 in these tissues. In another in vitro
      experiment of hepatocyte cultures, Cd exposure caused similar patterns of
      goldfish HSF1 and HSF2 mRNA expression and induction of the HSP70 protein. On the
      other hand, an examination of the characterization of recombinant proteins showed
      that HSF1 undergoes a conformation change induced by heat shock above 30  degrees
      C and approaches each other in the trimer, whereas HSF2 could not sense thermal
      stress directly. Furthermore, immune-blot analysis of HSFs showed that both
      monomers and trimmers of HSF1 were observed in cadmium-induced tissues, whereas
      HSF2 were all in monomeric. These results show that HSF1 and HSF2 play different
      roles in the transcription of heat shock proteins. 

PMID- 25592878
TI  - Effect of potential probiotic Rhodotorula benthica D30 on the growth performance,
      digestive enzyme activity and immunity in juvenile sea cucumber Apostichopus
      japonicus.
AB  - The effects of dietary addition of yeast Rhodotorula benthica (R. benthica) D30
      which isolated from local sea mud at levels of 0 (control), 10(5), 10(6) and
      10(7) CFU/g feed on the growth performance, digestive enzyme activity, immunity
      and disease resistance of juvenile sea cucumber Apostichopus japonicus were
      investigated. It was shown that dietary addition of R. benthica D30 significantly
      increased the growth rates of sea cucumbers (p < 0.05). The amylase activity,
      cellulase activity and alginase activity were increased for the animals from
      three probiotics treated groups. And with the supplemented concentration
      increased, the values of those digestive enzyme activities increased as well.
      Dietary addition of R. benthica D30 at the level of 10(7) CFU significantly
      increased the lysozyme, phagocytic and total nitric oxide synthase activity of A.
      japonicus (p < 0.05). While, the highest values of the phenoloxidase and alkaline
      phosphatase activity were found in sea cucumbers fed with R. benthica D30 at the
      level of 10(6) CFU. Whereas adding R. benthica D30 to diet had no significant
      effects on the total coelomocyte counts and acid phosphatase activity of A.
      japonicus (p > 0.05). It was observed that adding R. benthica D30 could
      significantly decrease the cumulative mortality of sea cucumbers. The present
      study demonstrated that dietary addition of R. benthica D30 could increase growth
      performance and some digestive enzyme activities, improve immunity and disease
      resistance of A. japonicus. And the medium (10(6) CFU) and high (10(7) CFU)
      additional levels showed better effects. It suggests that yeast R. benthica D30
      could be a good probiotic for aquaculture. 

PMID- 25592879
TI  - Suprapannus transverse caesarean section incision in morbidly obese women.

PMID- 25592880
TI  - Fast individual ancestry inference from DNA sequence data leveraging allele
      frequencies for multiple populations.
AB  - BACKGROUND: Estimation of individual ancestry from genetic data is useful for the
      analysis of disease association studies, understanding human population history
      and interpreting personal genomic variation. New, computationally efficient
      methods are needed for ancestry inference that can effectively utilize existing
      information about allele frequencies associated with different human populations
      and can work directly with DNA sequence reads. RESULTS: We describe a fast method
      for estimating the relative contribution of known reference populations to an
      individual's genetic ancestry. Our method utilizes allele frequencies from the
      reference populations and individual genotype or sequence data to obtain a
      maximum likelihood estimate of the global admixture proportions using the BFGS
      optimization algorithm. It accounts for the uncertainty in genotypes present in
      sequence data by using genotype likelihoods and does not require individual
      genotype data from external reference panels. Simulation studies and application
      of the method to real datasets demonstrate that our method is significantly times
      faster than previous methods and has comparable accuracy. Using data from the
      1000 Genomes project, we show that estimates of the genome-wide average ancestry
      for admixed individuals are consistent between exome sequence data and whole
      genome low-coverage sequence data. Finally, we demonstrate that our method can be
      used to estimate admixture proportions using pooled sequence data making it a
      valuable tool for controlling for population stratification in sequencing based
      association studies that utilize DNA pooling. CONCLUSIONS: Our method is an
      efficient and versatile tool for estimating ancestry from DNA sequence data and
      is available from https://sites.google.com/site/vibansal/software/iAdmix .

PMID- 25592881
TI  - Anticandidal activity of medicinal plants and Pseudomonas aeruginosa strains of
      clinical specimens.
AB  - This study was designed to investigate the in vitro anticandidal activity of some
      medicinal plants and Pseudomonas aeruginosa strains against Candida species. The
      antifungal activity of methanolic extracts of five medicinal plants, namely,
      Cinnamomum porrectum, Lippia nudiflora, Cestrum nocturnum, Trachyspermum ammi,
      and Sida carpinifolia were studied. The medicinal characteristics of these plants
      were compared with commercially used antibiotics. The antimicrobial assay was
      done by agar well diffusion and the broth dilution method. Among the plants used,
      T. ammi and C. nocturnum were found to be more potent than the others. Twenty P.
      aeruginosa strains were isolated from various clinical specimens. The total
      inhibitions obtained were found to be 47%, 38%, and 36% in blood agar, whereas in
      Sabouraud dextrose agar (SDA) the inhibitions were 57%, 48%, and 37%,
      respectively.

PMID- 25592882
TI  - Fluoroquinolone-resistant and extended-spectrum beta-lactamase-producing
      Escherichia coli from the milk of cows with clinical mastitis in Southern Taiwan.
AB  - BACKGROUND/PURPOSE: Escherichia coli is a common pathogen to cause clinical and
      subclinical mastitis in cows. A total of 57 E. coli isolates from raw milk from
      cows were characterized genetically and biochemically. METHODS: Extended-spectrum
      beta-lactamase (ESBL) genes, the mechanism for fluoroquinolone resistance, and
      variations in virulence genes and genomes of these E. coli isolates were
      investigated by the antimicrobial susceptibility test, simplex and multiplex
      polymerase chain reaction (PCR), and pulsed-field gel electrophoresis (PFGE).
      RESULTS: All E. coli isolates were resistant to cloxacillin (100%) and to a
      lesser extent (50%) to tetracycline, neomycin, gentamycin, ampicillin,
      ceftriaxone, cefotaxime (CTX), and ceftazidime (CAZ). Nearly 70% of the isolates
      were resistant to at least two antimicrobials and 28.1% carried AmpA and AmpC
      genes simultaneously. The predominant bla gene was blaTEM, followed by blaCMY,
      blaCTX, blaSHV, and blaDHA. Among the six (10.5%) ESBL-producing E. coli carrying
      blaCTX-M15, blaCTX-M55, or blaCTX-M14, two isolates 31 of ST410 in the ST23
      complex and 58 of ST167 in the ST10 complex were also resistant to ciprofloxacin,
      enrofloxacin, and levofloxacin, with mutations at codon 83 from serine to leucine
      and codon 87 from aspartic acid to asparagine in GyrA and at codon 80 from serine
      to isoleucine in ParC. These isolates were genetically diverse in pulsotype
      analysis, lacked toxin genes of human pathogenic E. coli and carried mostly the
      prevalent virulence genes fimH, papGII, and alpha-hemolysin. CONCLUSION: Lacking
      virulence genes examined, genetic diverse E. coli isolates are unrelated to human
      pathogenic E. coli. Enhancing sanitation in milk processing and transportation is
      needed to eliminate multidrug-resistant (MDR), fluoroquinolone-resistant, and
      ESBL-producing E. coli isolates.

PMID- 25592883
TI  - Cytotoxicity of obacunone and obacunone glucoside in human prostate cancer cells
      involves Akt-mediated programmed cell death.
AB  - Obacunone and obacunone glucoside (OG) are naturally occurring triterpenoids
      commonly found in citrus and other plants of the Rutaceae family. The current
      study reports the mechanism of cytotoxicity of citrus-derived obacunone and OG on
      human androgen-dependent prostate cancer LNCaP cells. Both limonoids exhibited
      time- and dose-dependent inhibition of cell proliferation, with more than 60%
      inhibition of cell viability at 100 MUM, after 24 and 48 h. Analysis of
      fragmentation of DNA, activity of caspase-3, and cytosolic cytochrome-c in the
      cells treated with limonoids provided evidence for activation of programmed cell
      death by limonoids. Treatment of LNCaP cells with obacunone and OG resulted in
      dose-dependent changes in expression of proteins responsible for the induction of
      programmed cell death through the intrinsic pathway and down-regulation of Akt, a
      key molecule in cell signaling pathways. In addition, obacunone and OG also
      negatively regulated an inflammation-associated transcription factor, androgen
      receptor, and prostate-specific antigen, and activated proteins related to the
      cell cycle, confirming the ability of limonoids to induce cytotoxicity through
      multiple pathways. The results of this study provided, for the first time, an
      evidence of the cytotoxicity of obacunone and OG in androgen-dependent human
      prostate cancer cells.

PMID- 25592884
TI  - What can be learned from adolescent time diary research.
AB  - Time use is increasingly being recognized as a determinant and indicator of
      adolescent well-being internationally. Three existing literature reviews of time
      use research with children and adolescents have identified time-use diaries as
      the preferred data collection method. Furthermore, they have encouraged
      researchers to examine multidimensional patterns of overall time use in large
      sample whole child populations to better understand the health, well-being, and
      quality of life of children and young people. However, these three existing
      reviews differ in the time frames covered; the age ranges targeted; the
      categories of time use examined; and the time-use data collection and analysis
      methods used. This study aimed to map the extent and nature of time diary studies
      with well adolescents (aged 10-19 years) and the use of person-centered data
      analysis of overall time use as a multidimensional unit. Finally, it explores
      whether and how the included studies analyzed the relationship between time use
      and health, well-being, and quality of life. A scoping review method was employed
      using Arksey and O'Malley's five-step framework. Thirty-three studies met the
      inclusion criteria. Most studies were secondary analyses of cross-sectional
      population-level time-use or lifestyle survey data. One-third of studies (n = 11)
      captured data representing 24 hours of the day. Two studies (6%) used person
      centered analyses, while six studies (18%) empirically examined time use in
      relation to health and well-being. No studies examined adolescent 24-hour time
      use and quality of life. Adolescent time-use researchers are encouraged to be
      explicit in identifying the stage of adolescence to which their studies relate;
      capture 24-hour time-use data; analyze overall activity patterns as
      multidimensional units using person-centered methods; and use robust, reliable,
      valid, sensitive, and age-appropriate instruments to empirically examine time use
      and health, well-being, and quality of life. Through this, healthy patterns of
      everyday activity for adolescents can be illuminated. 

PMID- 25592885
TI  - Health Education England, Local Education and Training Boards (LETBs) and reform
      of healthcare education: implications for surgical training.
AB  - BACKGROUND: National Health Service (NHS) reforms have changed the structure of
      postgraduate healthcare education and training. With a Government mandate that
      promotes multi-professional education and training aligned with policy driven
      initiatives, this article highlights concerns over the impact that these changes
      may have on surgical training. DISCUSSION: The creation of Health Education
      England (HEE) and its local education and training boards (LETBs), which are
      dominated by NHS healthcare providers, should result in greater accountability of
      employers in workforce planning, enhanced local responsibility and increased
      transparency of funding allocation. However, these changes may also create a
      potential poacher-turned-gamekeeper role of employers, who now have
      responsibility for junior doctors' training. Analysis of LETB membership reveals
      a dearth of representation of surgeons, who comprise only 2% of board members,
      with the input of trainees also seemingly overlooked. A lack of engagement with
      the LETBs by the independent sector is a concern with increasing numbers of
      training opportunities potentially being lost as a result.The new system also
      needs to recognise the specific training needs required by the craft specialties
      given the demands of technical skill acquisition, in particular regarding the
      provision of simulation training facilities and trainer recognition. However,
      training budget cuts may result in a disproportionate reduction of funding for
      surgical training. Surgical training posts will also be endangered, opportunities
      for out-of-programme experience and research may also decline and further costs
      are likely to be passed onto the trainee. SUMMARY: Although there are several
      facets to the recent reforms of the healthcare education and training system that
      have potential to improve surgical training, concerns need to be addressed.
      Engagement from the independent sector and further clarification on how the LETBs
      will be aligned with commissioning services are also required. Surgical training
      is in danger of taking a back seat to Government mandated priorities.
      Representation of trainees and surgeons on LETB committees is essential to ensure
      a surgical viewpoint so that the training needs of the future consultant
      workforce meet the demands of a 21st century health service.

PMID- 25592886
TI  - Weaning China off organs from executed prisoners.

PMID- 25592887
TI  - Warning sounded over commercial ultrasound in pregnancy.

PMID- 25592888
TI  - Cuba: health lessons not under embargo.

PMID- 25592890
TI  - Russia's drug production plans hit by economic situation.

PMID- 25592892
TI  - The enigmatic illness and death of Constance, wife of Oscar Wilde.

PMID- 25592893
TI  - Priorities in Ebola research--a view from the field.

PMID- 25592894
TI  - Safeguarding the ACA's gains for women.

PMID- 25592895
TI  - Improving midwifery care worldwide.

PMID- 25592896
TI  - Improving midwifery care worldwide.

PMID- 25592897
TI  - Improving midwifery care worldwide.

PMID- 25592898
TI  - Improving midwifery care worldwide--authors' reply.

PMID- 25592903
TI  - Coordinated efforts in the reporting of global physical activity.

PMID- 25592904
TI  - Fever and cough without pulmonary abnormalities on CT: relapsing polychondritis
      restricted to the airways.

PMID- 25592905
TI  - Lives on the line: sex work in sub-Saharan Africa.

PMID- 25592906
TI  - Cuba-US relations: will public health lead the way?

PMID- 25592908
TI  - The effects of calcipotriol on the dendritic morphology of human melanocytes
      under oxidative stress and a possible mechanism: is it a mitochondrial protector?
AB  - BACKGROUND: Vitiligo is an acquired pigmentary disorder of unknown etiology that
      is clinically characterized by the development of white macules in the skin
      related to the selective loss of melanocytes in those areas. Evidence shows that
      mitochondria might be a unifying target of reactive oxygen species (ROS)
      generation, cytokine production, catecholamine release and/or alteration of
      Ca(2+) metabolism that leads to melanocyte loss. OBJECTIVE: To assess the
      protective effect of calcipotriol on mitochondria of human melanocytes by
      investigating their dendritic morphology under oxidative stress. METHODS: Human
      melanocytes were treated with 0.05% H2O2 as well as various concentrations of
      calcipotriol, after which the retraction velocity of melanocyte dendrites was
      assessed. Detection of malondialdehyde (MDA) and superoxide dismutase (SOD) was
      performed as were the mitochondrial membrane potential (MMP) and intracellular
      calcium concentration ([Ca(2+)]i). Ultrastructural changes of mitochondria in
      melanocytes were observed by transmission electron microscopy. In addition, the
      expression of Beclin1, microtubule-associated protein 1 light chain 3 (LC3),
      dynamin related protein 1 (Drp1), mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2),
      which are related to autophagy and mitochondrial dynamics, were analyzed by
      Western blot. RESULTS: Calcipotriol reduced the retraction velocity of melanocyte
      dendrites. In addition, calcipotriol, from 20nM to 80nM, decreased the level of
      MDA, increased the activity of SOD, suppressed the reduction of MMP and recovered
      Ca(2+) homeostasis by reducing [Ca(2+)]i in a concentration-dependent manner.
      Observation by transmission electron microscopy suggested that calcipotriol might
      reduce the injury of mitochondria in melanocytes under oxidative stress.
      Furthermore, the expression of Beclin1, LC3-II/LC3-I, Mfn2 and Drp1 was higher in
      the calcipotriol-treated melanocytes than in the control or H2O2-treated
      melanocytes. The level of Mfn1 was almost unchanged, but was higher at a
      concentration of 80nM calcipotriol than in any other condition. The expression of
      Mfn2 and Drp1 decreased with increasing calcipotriol concentration. CONCLUSION:
      Our study demonstrates the antioxidative effect of calcipotriol on melanocytes
      against oxidative damage. Moreover, calcipotriol could be a promising drug
      delivery strategy to protect melanocytes against oxidative damage in vitiligo
      through autophagy or mitophagy.

PMID- 25592907
TI  - Whole brain irradiation with hippocampal sparing and dose escalation on multiple
      brain metastases: Local tumour control and survival.
AB  - PURPOSE: Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple
      brain metastases may prevent treatment-related cognitive decline, compared to
      standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual
      metastases may further improve the outcome. Here, we present initial data
      concerning local tumour control (LTC), intracranial progression-free survival
      (PFS), overall survival (OS), toxicity and safety for this new irradiation
      technique. METHODS AND MATERIALS: Twenty patients, enrolled between 2011 and
      2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98% to hippocampus <= 9
      Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated
      arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated
      bidimensionally along the two largest diameters in contrast-enhanced three
      dimensional T1-weighed MRI. RESULTS: Median follow-up was 40 weeks. The median
      time to progression of boosted metastases has not been reached yet, corresponding
      to a LTC rate of 73%. Median intracranial PFS was 40 weeks, corresponding to a 1
      year PFS of 45.3%. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60%.
      No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed.
      Dmean to the bilateral hippocampi was 6.585 Gy +/- 0.847 (alpha/beta = 2 Gy). Two
      patients developed a new metastasis in the area of hippocampal avoidance.
      CONCLUSION: HA-WBRT (simultaneous integrated protection, SIP) with SIB to
      metastases is a safe and tolerable regime that shows favorable LTC for patients
      with multiple brain metastases, while it has the potential to minimize the side
      effect of cognitive deterioration.

PMID- 25592909
TI  - Study of the succession of microbial communities for sulfur cycle response to
      ecological factors change in sediment of sewage system.
AB  - The biological reaction process of sulfur in biofilms and sediments causes
      serious problems of corrosion and odor in sewage systems. This study aims to
      reveal the distribution and shift of microbial diversity that survives inside the
      sediment in response to surrounding changes in sewage systems. The successions of
      microbial community were compared via denaturing gradient gel electrophoresis and
      by constructing phylogenetic trees via maximum likelihood method. The results
      indicated that the shift of microbial diversity is not significant along the
      vertical layer inside the sediment. The influences of sediment accumulation time
      on the shift in microbial diversity are evident, particularly with the switch of
      the accumulation stage. Implementing a control strategy for oxygen injection and
      nitrate addition evidently inhibits and stimulates some dominant sulfate-reducing
      bacterial strains in the sediment. The diversity in the total bacteria is
      positively related with ORP, dissolved oxygen, and sulfide concentration. 

PMID- 25592910
TI  - Nanoparticles in wastewater treatment plants: a novel acute toxicity test for
      ciliates and its implementation in risk assessment.
AB  - Nanomaterial (NM) release into wastewater treatment plants (WWTPs) is inevitable
      due to increased production and application throughout past decades and in the
      future. Concern arose about environmental risks and impact on activated sludge.
      Environmental risk assessment (ERA) for NMs according to established guidelines
      is considered not suitable, because NMs exhibit unique characteristics. For
      hazard identification on activated sludge, standard test organisms for aquatic
      toxicity testing are not meaningful. In this study, we developed an acute
      toxicity test for ciliates (Paramecium tetraurelia) as representatives of the
      important functional group of microbial predators and filter feeders. We chose
      silver nanoparticles (nAg) exemplarily for ion releasing nanoparticles and
      regarded toxicity by ions as well. Our results indicate that ions are more toxic
      (EC50 0.73 mg/L) than nanoparticles themselves (EC50 2.15 mg/L). However, nAg
      must be considered as a source of ions and requires size, surface coating, and
      compartment-specific ERA. We strived to develop such ERA based on our results,
      modeled environmental concentration data from literature, and surface area
      concentrations. Results indicated a probable risk toward activated sludge. This
      likely has effects on effluent water quality. We conclude that carefully modeled
      environmental concentrations are vital for more exact ERA for nAg and other NMs.

PMID- 25592911
TI  - The three steps of the carbonate biogenic dissolution process by microborers in
      coral reefs (New Caledonia).
AB  - Biogenic dissolution of carbonates by microborers is one of the main destructive
      forces in coral reefs and is predicted to be enhanced by eutrophication and ocean
      acidification by 2100. The chlorophyte Ostreobium sp., the main agent of this
      process, has been reported to be one of the most responsive of all microboring
      species to those environmental factors. However, very little is known about its
      recruitment, how it develops over successions of microboring communities, and how
      that influences rates of biogenic dissolution. Thus, an experiment with dead
      coral blocks exposed to colonization by microborers was carried out on a reef in
      New Caledonia over a year period. Each month, a few blocks were collected to
      study microboring communities and the associated rates of biogenic dissolution.
      Our results showed a drastic shift in community species composition between the
      4th and 5th months of exposure, i.e., pioneer communities dominated by large
      chlorophytes such as Phaeophila sp. were replaced by mature communities dominated
      by Ostreobium sp. Prior the 4th month of exposure, large chlorophytes were
      responsible for low rates of biogenic dissolution while during the community
      shift, rates increased exponentially (*10). After 6 months of exposure, rates
      slowed down and reached a "plateau" with a mean of 0.93 kg of CaCO3 dissolved per
      m(2) of reef after 12 months of exposure. Here, we show that (a) Ostreobium sp.
      settled down in new dead substrates as soon as the 3rd month of exposure but
      dominated communities only after 5 months of exposure and (b) microbioerosion
      dynamics comprise three distinct steps which fully depend on community
      development stage and grazing pressure. 

PMID- 25592912
TI  - Air pollution by allergenic spores of the genus Alternaria in the air of central
      and eastern Europe.
AB  - Spores of the genus Alternaria belong to one of the most prevailing constituents
      of the air in all regions of the world. They form infectious inoculum of numerous
      plant species as well as severe inhaled allergies. The aim of this study was to
      compare the biological pollution with Alternaria spores of the air of 12 cities
      located in central and eastern Europe. The experiment was done in 2010 and it
      covered the territory of Latvia (LV), Lithuania (LT), Poland (PL) and Ukraine
      (UA). The spores were counted using an identical method and standard equipment (7
      day Lanzoni volumetric sampler) followed by extensive statistical calculations.
      The timing of the day of maximum concentration changed mainly along the N-S
      direction and had a positive correlation with latitude. The most important factor
      determining the increase in Alternaria spore concentration was the temperature,
      whereas other weather parameters were not related or of low significance.
      Regardless of geographical location, the first phase of the season (0-0.9 % of
      Alternaria spores in the air) was the longest (up to 60 days) and the last (97.5
      to 99 %) was the shortest (22 days or less). The means of daily concentrations of
      Alternaria spores ranged from 11 spores m(-3) in Klaipeda (LT, Baltic Sea coast)
      to 187 in Poznan (west PL, agricultural plain). The threshold value of 80 spores
      m(-3) that triggers the first allergy symptoms was exceeded in 8 to 86 days
      (Vinnitsa, UA, temperate continental, forest-steppes region). There were
      considerable differences between the highest number of spores per cubic metre of
      air, varying from 139 in the north (Klaipeda, LT) to 2,295 in central west
      (Poznan, PL). The biological pollution by Alternaria spores in several places of
      central and eastern Europe was high; the number of days exceeding the threshold
      value of 300 spores m(-3) connected with serious health problems of atopic people
      ranged from 0 to 1 on the north (LV, LT) to 29 in central west (Poznan, PL).

PMID- 25592913
TI  - Effect of plant growth-promoting rhizobacteria inoculation on cadmium (Cd) uptake
      by Eruca sativa.
AB  - Microbe-assisted phyto-remediation approach is widely applied and appropriate
      choice to reduce the environmental risk of heavy metals originated from
      contaminated soils. The present study was designed to screen out the nested
      belongings of Eruca sativa plants and Pseudomonas putida (ATCC 39213) at varying
      cadmium (Cd) levels and their potential to deal with Cd uptake from soils. We
      carried out pot trial experiment by examining the soil containing E. sativa
      seedlings either treated with P. putida and/or untreated plants subjected to
      three different levels (ppm) of Cd (i.e., 150, 250, and 500). In all studied
      cases, we observed an increase in Cd uptake for E. sativa plants inoculated with
      P. putida than those of un-inoculated plants. Cd toxicity was assessed by
      recording different parameters including stunted shoot growth, poor rooting, and
      Cd residual levels in the plants that were not inoculated with P. putida.
      Significant difference (p < 0.05) of different growth parameters for inoculated
      vs non-inoculated plants was observed at all given treatments. However, among the
      different treatments, E. sativa exhibited increased values for different growth
      parameters (except proline contents) at lower Cd levels than those of their
      corresponding higher levels, shoot length (up to 27 %), root length (up to 32 %),
      whole fresh plant (up to 40 %), dry weight (up to 22 %), and chlorophyll contents
      (up to 26 %). Despite the hyperaccumulation of Cd in whole plant of E. sativa, P.
      putida improved the plant growth at varying levels of Cd supply than those of
      associated non-inoculated plants. Present results indicated that inoculation with
      P. putida enhanced the Cd uptake potential of E. sativa and favors the healthy
      growth under Cd stress.

PMID- 25592914
TI  - Fluorescence spectroscopy to study dissolved organic matter interactions with
      agrochemicals applied in Swiss vineyards.
AB  - UV/Vis fluorescence spectroscopy was used to study the possible interactions of
      dissolved organic matter (DOM) with the herbicide glyphosate and copper-based
      fungicide used in vineyards. The study focused on the role of DOM in the
      transport of these micropollutants from parcels to surface waters (river, lake).
      Soil solution and river water samples were collected in the Lavaux vineyard area,
      western Switzerland. Their fluorescence excitation emission matrices (EEM) were
      decomposed using parallel factor (PARAFAC) analysis, and compared to their
      content in glyphosate and copper. PARAFAC analysis of EEM of both types of
      samples showed the contribution of protein-like and humic-like fluorophores. In
      soil water samples, complexes between fulvic-like and humic-like fluorophores of
      DOM, copper, and glyphosate were likely formed. In surface water, DOM-copper and
      glyphosate-copper interactions were observed, but not between glyphosate and DOM.

PMID- 25592915
TI  - Changes in the parameters of gait after a mechanical debridement of a plantar
      callosities.
AB  - INTRODUCTION: Plantar callosities are a common cause of pain in the forefoot and
      also a cause of alterations in plantar pressure. Mechanical debridement with a
      scalpel can relieve pain and increase functional capacity. OBJECTIVE: The aim of
      the study was to analyse if debridement of plantar callosities and corns modify
      walking. METHODS: Thirty four patients with plantar foot pain due to callosities
      and corns, and up to 5 in the visual analogical scale (VAS) of pain, (20 women,
      age 29 +/- 11.57 years) were analysed by taking into account the changes of their
      gait. The outcome measurement was the VAS scale and the Win-track system, cycle
      of the gait(milliseconds), angle(degrees), cadence(number/minutes) and
      step(centimetres) were measured, 24 h before and after the debridement with a
      scalpel. RESULTS: There were significant differences in foot pain (mean 67.7, p <
      0.001) but there were no significant differences in measures of gait variables
      before the debridement of the callosities, and 24 h after the procedure, being
      all those above 0.05. CONCLUSIONS: Our study shows that the debridement with
      scalpel does not change the variables of the gait 24 h after the procedure.

PMID- 25592916
TI  - Anesthesia and neuroimaging: investigating the neural correlates of
      unconsciousness.
AB  - In the past 15 years, rapid technological development in the field of
      neuroimaging has led to a resurgence of interest in the study of consciousness.
      However, the neural bases of consciousness and the boundaries of unconscious
      processing remain poorly understood. Anesthesia combined with functional
      neuroimaging presents a unique approach for studying neural responses as a
      function of consciousness. In this review we summarize findings from functional
      neuroimaging studies that have used anesthetic drugs to study cognition at
      different levels of conscious awareness. We relate the results to those of
      psychophysical studies of cognition and explore their potential usefulness in
      interpreting clinical findings from studies of non-responsive patients. 

PMID- 25592917
TI  - Predicting performance expectations from affective impressions: linking affect
      control theory and status characteristics theory.
AB  - Affect control theory (ACT) and status characteristics theory (SCT) offer
      separate and distinct explanations for how individuals interpret and process
      status- and power-relevant information about interaction partners. Existing
      research within affect control theory offers evidence that status and power are
      related to the affective impressions that individuals form of others along the
      dimensions of evaluation and potency, respectively. Alternately, status
      characteristics theory suggests that status and power influence interaction
      through the mediating cognitive construct of performance expectations. Although
      both theories have amassed an impressive amount of empirical support, research
      has yet to articulate theoretical and empirical connections between affective
      impressions and performance expectations. The purpose of our study is to address
      this gap. Elaborating a link between ACT and SCT in terms of their central
      concepts can serve as a stepping stone to improving the explanatory capacity of
      both theories, while providing a potential bridge by which they can be employed
      jointly. 

PMID- 25592918
TI  - Latent Class Models in action: bridging social capital & Internet usage.
AB  - This paper explores how Latent Class Models (LCM) can be applied in social
      research, when the basic assumptions of regression models cannot be validated. We
      examine the usefulness of this method with data collected from a study on the
      relationship between bridging social capital and the Internet. Social capital is
      defined here as the resources that are potentially available in one's social
      ties. Bridging is a dimension of social capital, usually related to weak ties
      (acquaintances), and a source of instrumental resources such as information. The
      study surveyed a stratified random sample of 417 inhabitants of Lisbon, Portugal.
      We used LCM to create the variable bridging social capital, but also to estimate
      the relationship between bridging social capital and Internet usage when we
      encountered convergence problems with the logistic regression analysis. We
      conclude by showing a positive relationship between bridging and Internet usage,
      and by discussing the potential of LCM for social science research. 

PMID- 25592920
TI  - (Dis)placing trust: the long-term effects of job displacement on generalised
      trust over the adult lifecourse.
AB  - Increasing rates of job displacement (i.e. involuntary job loss from redundancy,
      downsizing, restructuring) have been suggested to be a key driver of declining
      macro-levels of generalised trust. This article undertakes the first test of how
      job displacement affects individuals' tendencies to (dis)trust over the adult
      lifecourse, using two-waves of the Great Britain National Child Development Study
      cohort data, on a sample of n=6840 individuals. Applying both lagged dependent
      variable logistic regression and two-wave change-score models, experiencing job
      displacement between the ages of 33 and 50 appears to significantly scar
      individuals' generalised trust, with depressed trust observable at least nine
      years after the event occurred. However, this effect is dependent on the value an
      individual places on work: the greater the attachment to employment the stronger
      the negative effect of displacement. A range of mediators, such as physical
      health, mental well-being, and personal efficacy, do not appear to account for
      the effect. 

PMID- 25592919
TI  - Surgical sterilization, regret, and race: contemporary patterns.
AB  - Surgical sterilization is a relatively permanent form of contraception that has
      been disproportionately used by Black, Hispanic, and Native American women in the
      United States in the past. We use a nationally representative sample of 4592
      women ages 25-45 to determine whether sterilization continues to be more common
      and consequential by race for reproductive-age women. Results indicate that
      Native American and Black women are more likely to be sterilized than non
      Hispanic White women, and Hispanic and Native American women are more likely than
      non-Hispanic White women to report that their sterilization surgeries prevent
      them from conceiving children they want. Reasons for sterilization differ
      significantly by race. These findings suggest that stratified reproduction has
      not ended in the United States and that the patterns and consequences of
      sterilization continue to vary by race. 

PMID- 25592921
TI  - Universalism under siege? Exploring the association between targeting, child
      benefits and child poverty across 26 countries.
AB  - The long-standing wisdom that universally designed benefits outperform targeted
      benefits in terms of poverty reduction has come under siege. Recent empirical
      studies tend to find that targeting is not necessarily associated anymore with
      lower levels of poverty reduction. In this study, we investigate for a broad set
      of European countries (1) the relationship between child benefits and child
      poverty reduction; (2) whether a universal or targeted approach is more effective
      in reducing child poverty; and (3) the causal mechanisms explaining the link
      between (1) and (2). In doing so, we take into account the general
      characteristics of the child benefit system, the size of the redistributive
      budget and the generosity of benefit levels. In contrast to previous studies, we
      construct an indicator of targeting that captures the design instead of the
      outcomes of child benefit systems. We find that targeting towards lower incomes
      is associated with higher levels of child poverty reduction, conditional on the
      direction of targeting and the characteristics of the benefit system. 

PMID- 25592922
TI  - Career pathways for temporary workers: exploring heterogeneous mobility dynamics
      with sequence analysis.
AB  - Because temporary jobs are time-delimited, their implications for workers'
      economic security depend not only on their current characteristics, but also
      their place in longer-term patterns of mobility. Past research has typically
      asked whether temporary jobs are a bridge to better employment or trap workers in
      ongoing insecurity, investigating this question by analyzing single transitions.
      We demonstrate that this approach is ill-suited to assessing the often more
      complex and turbulent employment patterns characteristic of temporary workers.
      Our analysis instead employs sequence methods to compare a representative sample
      of temporary workers' month-by-month mobility patterns through 8 potential
      (non)employment states over five years. We derive a typology of trajectories and
      describe their relative precariousness in relation to employment stability and
      wage and earnings levels and growth. While some of the pathways correspond quite
      closely to frameworks used by past research, others reveal new and important
      distinctions. Multinomial logit models reveal job, employer, and worker
      characteristics associated with different pathways. Age, gender, and type of
      temporary work stand out as important factors shaping subsequent mobility
      patterns. 

PMID- 25592923
TI  - Neighbourhood effects on educational attainment of adolescents, buffered by
      personality and educational commitment.
AB  - Research has repeatedly shown that neighbourhood disadvantage negatively
      influences individual educational outcomes. However, the great variation in
      outcomes indicates substantial unobserved heterogeneity. Looking at the rates of
      obtaining a basic educational qualification, the hypothesis is that individual
      traits of adolescents can buffer neighbourhood effects. First, adolescents with a
      more resilient personality may be better able to cope with neighbourhood
      adversity. And second, educational commitments might buffer adolescents from
      negative neighbourhood influences. These hypotheses are tested employing survival
      analysis, using six wave panel data, containing information on ten years of
      adolescents' lives. The results show that resilients experience no negative
      influence of neighbourhood disadvantage, while both undercontrollers and
      overcontrollers do. And, the stronger adolescents' educational commitments, the
      less they experience the negative effect of neighbourhood adversity. In sum,
      neighbourhood effects are found, but not for everybody. 

PMID- 25592924
TI  - The increasing unemployment gap between the low and high educated in West
      Germany. Structural or cyclical crowding-out?
AB  - This paper addresses trends in education-specific unemployment risks at labor
      market entry in West Germany from the mid-1970s to the present. In line with
      previous research it shows that vocationally qualified school-leavers have
      relatively lower unemployment risks than school-leavers with general education.
      Over time, the gap in unemployment risks between the low-educated and medium- and
      highly educated labor market entrants substantially widened for both sexes. The
      literature identifies two different mechanisms for this trend: structural or
      cyclical crowding out. While in the former scenario low-educated become
      increasingly unemployed due to an oversupply of tertiary graduates and
      displacement from above, in the latter their relative unemployment risk varies
      with the business cycle. The results provide evidence for cyclical rather than
      structural crowding-out in West Germany. Since macroeconomic conditions became
      generally worse over time, this strongly explains the widening unemployment gap
      between the low-educated and all other education groups. 

PMID- 25592925
TI  - State liberalism, female supervisors, and the gender wage gap.
AB  - Whereas some are concerned that the gender revolution has stalled, others note
      the rapid increase in women's representation in the ranks of management, and the
      reduction of wage inequality in larger and more active welfare states. Although
      these latter trends portend an attenuation of gender inequality, their effects on
      the gender pay gap in the U.S. are understudied due to data limitations, or to
      the assumption that in the U.S. pay is determined by market forces. In this study
      we extend research on the determinants of the gender wage gap by examining sex-of
      supervisor effects on subordinates' pay, and to what degree the state's
      commitment to equality conditions this relationship. We pooled the 1997 and 2002
      National Study of the Changing Workforce surveys to estimate hierarchical models
      of reporting to a female supervisor and wages, with theoretically important
      predictors at the individual level, and at the state of residence (an index
      composed of women's share of legislators, a measure of the liberal leanings of
      the state, and the size of the public sector relative to the labor force). We
      found that state effects on pay were mixed, with pay generally rising with state
      liberalism on the one hand. On the other hand, working for a female boss
      significantly reduced wages. We discussed the theoretical implications of our
      results, as well as the need for further study of the career effects on
      subordinates as women increasingly enter the ranks of management. 

PMID- 25592926
TI  - Measuring the level of social support using latent class analysis.
AB  - Different instruments have been used to measure social support in epidemiological
      studies of which the most widely used is the Medical Outcomes Study Social
      Support Scale (SSS-MOS). However, these studies lack measures of the level of
      social support on health risks. We used latent class analysis (LCA) to
      distinguish subgroups with different levels of perceived social support and
      tested the consistency of these subgroups by their associations with the
      prevalence of Common Mental Disorders (CMD). This is a cross-sectional study of
      1013 mothers living in the city of Salvador, Brazil in which psychosocial data
      were collected through home visits using the SSS-MOS and the Self Reporting
      Questionnaire-20. For each dimension of social support analysed here, we selected
      models with two classes using LCA. Multivariate logistic regression models were
      used to estimate the association between participants' perceived social support
      and the prevalence of CMD to verify the consistency of the groups defined by LCA.
      There was a clear difference in the reporting of perceived social support between
      those classified as high or low using LCA. The probability of perceiving several
      types of social support was lower in the subgroup classified as low level of
      social support (13.7-59.8%), and it was much higher in the group classified as
      high level of social support (84.3-98%). A greater prevalence of CMD was found
      among mothers with lower levels of social support. LCA seems to be a useful tool
      to improve measurement of perceived social support by separation into two levels
      in which the lower level is associated with an increased prevalence of CMD. 

PMID- 25592927
TI  - The use of multilevel modeling and the level two residual file to explore the
      relationship between middle years programme student performance and diploma
      programme student performance.
AB  - Multilevel modeling has recently found a substantial niche in the context of
      educational research, although several details about the methodological
      application of these models have yet to be explored in an achievement data
      framework. This paper makes use of data provided by the International
      Baccalaureate (IB) in order to investigate modeling decisions and certain
      applications of the level two residual file in an effort to increase
      understanding about the way linear and logistic multilevel models function. The
      focus of this research is on the relationship between performances in two IB
      programmes: the Middle Years Programme (MYP) and the Diploma Programme (DP). The
      impact of predictors on the interpretation of the unconditional and conditional
      variance-covariance matrix as well as the reliability coefficients is discussed.
      Empirical findings suggest that students who perform better during MYP moderation
      tend to perform better on DP exams. 

PMID- 25592928
TI  - Liking and disliking minority-group classmates: explaining the mixed findings for
      the influence of ethnic classroom composition on interethnic attitudes.
AB  - Research on the influence of the number of ethnic minority group classmates on
      majority group students' interethnic attitudes produced conflicting results. With
      data from 728 early adolescents, we found that the effect of the ethnic class
      composition depends on two opposing student-level mechanisms. First, majority
      group students who liked a larger number of minority group classmates developed
      more positive attitudes toward minority groups. Second, students who disliked a
      larger number of outgroup classmates developed more negative outgroup attitudes.
      In our sample, these two effects neutralized each other because the sample
      consisted of about the same number of students that liked most of their outgroup
      classmates and students that disliked most outgroup classmates. Results were
      consistent in cross-sectional and longitudinal analyses. These results support a
      new interpretation of the mixed findings in past research, suggesting that past
      studies may have differed in the number of students who liked and disliked
      outgroup classmates. 

PMID- 25592929
TI  - Cultural capital in context: heterogeneous returns to cultural capital across
      schooling environments.
AB  - This paper tests two competing explanations of differences in returns to cultural
      capital across schooling environments: Cultural reproduction (cultural capital
      yields a higher returns in high-achieving environments than in low-achieving
      ones) and cultural mobility (cultural capital yields higher returns in low
      achieving environments). Using multilevel mixture models, empirical results from
      analyses based on PISA data from three countries (Canada, Germany, and Sweden)
      show that returns to cultural capital tend to be higher in low-achieving
      schooling environments than in high-achieving ones. These results principally
      support the cultural mobility explanation and suggest that research should pay
      explicit attention to the institutional contexts in which cultural capital is
      converted into educational success. 

PMID- 25592930
TI  - Material hardship and 529 college savings plan participation: the mitigating
      effects of Child Development Accounts.
AB  - Experience of material hardship can adversely affect a family's ability to make
      long-term investments in children's development. We examine whether material
      hardship is associated with one indicator of such investments: participation in a
      tax-advantaged college savings plan (529 plan). Data for this study come from the
      SEED for Oklahoma Kids (SEED OK) experiment, an intervention that offers Child
      Development Accounts with financial incentives to encourage the accumulation of
      college savings for children from the time of their birth. Results show that
      material hardship is negatively associated with 529-plan participation, and this
      association varies by treatment status. At all levels of material hardship,
      treatment-group mothers are more likely to hold accounts than control-group
      mothers. These findings suggest that CDAs can be a useful policy tool to support
      families' financial preparation for college. 

PMID- 25592931
TI  - Occupational stratification, job-mismatches, and child poverty: understanding the
      disadvantage of Black immigrants in the US.
AB  - This study examines the implications of occupational stratification and job
      mismatches for the welfare of children, using data from the 2005-2009 American
      Community Survey. The results show that Black children of immigrants have
      household heads that are more likely to have occupations with low SEI scores than
      children in US-born households. More importantly, they demonstrate that
      intersections between parental job-mismatches and employment in the bottom rather
      than upper levels of the occupational distribution have important implications
      for understanding poverty differences among children. Job mismatches within
      occupations with low SEI scores are associated with greater poverty risks among
      Black than White, Asian, or Hispanic children of immigrants. However, racial
      poverty disparities are considerably lower among children with household heads in
      the highest occupational strata. 

PMID- 25592932
TI  - Towards climate justice: how do the most vulnerable weigh environment-economy
      trade-offs?
AB  - The world's poor are especially vulnerable to environmental disasters, including
      the adverse consequences of climate change. This creates a challenge for climate
      justice advocates who seek to ensure that those least responsible for causing
      climate change do not bear unwanted burdens of mitigation. One way to promote
      climate justice could be to pay particular attention to the environmental policy
      preferences of citizens from poorer, lower-emitting countries. This paper
      examines opinions on environment-economy trade-offs and willingness to make
      personal financial contributions to protect the environment among residents of 42
      developed and developing countries using data from the 2005-2008 World Values
      Survey, the 2010 Climate Risk Index, and World Bank development indicators.
      Results reveal that individuals in developing countries are less likely to
      support policies to prioritize environmental protection over economic growth but
      are more willing to donate personal income for pro-environmental efforts compared
      to citizens of more developed nations. 

PMID- 25592933
TI  - When everyone goes to college: the causal effect of college expansion on
      earnings.
AB  - In this study, we estimate the causal effect of college expansion on earnings
      using the example of South Korea in the 1990s where the college enrollment rate
      increased from just over thirty percent to over eighty percent over a fifteen
      years period. We compare the pre-expansion cohort and the post-expansion cohort
      in order to identify those who would attend college because of the expansion but
      would not attend otherwise (compliers). We, then, estimate compliers' earnings
      gain from the college expansion relative to the earnings changes of two control
      groups: those who either would or would not go to college regardless of college
      expansion (always-takers and never-takers). We find a striking gendered pattern;
      for men, the earnings return to college expansion is moderate and mostly driven
      by the increasing skill price, whereas, for women, the return is significantly
      large even net of the skill price change. 

PMID- 25592934
TI  - Status, emotional displays, and the relationally-based evaluation of criminals
      and their behavior.
AB  - This research uses status characteristics theory to expand our knowledge of the
      effects of status variables (e.g., race, education) and emotional displays on the
      antecedents of sentencing - evaluations of offender dangerousness and offense
      seriousness. We present a theoretical formulation that combines three areas of
      status characteristics research - reward expectations, individual evaluative
      settings and valued personal characteristics. The result is a quantitative
      measure that aggregates relative differences in demographic and emotional
      characteristics between offenders and their victims. The significance of this
      expectation advantage measure (e) in predicting evaluations of offender
      dangerousness and offense severity is tested using data from a vignette study. We
      find empirical support that expectation advantage significantly predicts these
      sentencing antecedents but not sentencing outcomes directly. We conclude by
      discussing the implications of our findings for future status and criminological
      research. 

PMID- 25592935
TI  - Chips off the old blocks? The political participation patterns of parents and
      children in Italy.
AB  - This article studies the relationship between the political participation of
      parents and children in Italy, a country for which no empirical evidence on the
      topic is available and that has particular characteristics in terms of household
      dynamics and patterns of political participation. The analyses are based on a
      sample of 12,802 children from 14 to 19 years old and their parents, drawn from
      the "Multipurpose survey - Aspects of daily life", collected by the Italian
      National Institute of Statistics. The results show that the political
      participation of children is strongly associated with that of their parents; that
      maternal participation is of somewhat greater relevance to the participation of
      both sons and daughters compared to that of fathers; and that the parents' level
      of education is not associated with the likelihood of the child participating,
      net of parental participation.

PMID- 25592936
TI  - The power of a paired t-test with a covariate.
AB  - Many researchers employ the paired t-test to evaluate the mean difference between
      matched data points. Unfortunately, in many cases this test in inefficient. This
      paper reviews how to increase the precision of this test through using the mean
      centered independent variable x, which is familiar to researchers that use
      analysis of covariance (ANCOVA). We add to the literature by demonstrating how to
      employ these gains in efficiency as a factor for use in finding the statistical
      power of the test. The key parameters for this factor are the correlation between
      the two measures and the variance ratio of the dependent measure on the
      predictor. The paper then demonstrates how to compute the gains in efficiency a
      priori to amend the power computations for the traditional paired t-test. We
      include an example analysis from a recent intervention, Families Preparing the
      New Generation (Familias Preparando la Nueva Generacion). Finally, we conclude
      with an analysis of extant data to derive reasonable parameter values. 

PMID- 25592937
TI  - The impact of cumulative family risks on various levels of food insecurity.
AB  - The study uses the Fragile Families and Child Well-being Study (N=2025) to
      examine the relationship between four cumulative family risk indices and refined
      measures of food hardship: marginal food security, low food security, and very
      low food security. Regression analyses indicate that cumulative family risk
      indices are useful in differentiating various levels of food insecurity.
      Specifically, the maternal poor health and risky health behaviors index is
      pertinent for distinguishing (1) food insecure from marginal food secure
      households and (2) very low food secure from low food secure households. In
      addition, the financial strain index is pertinent for differentiating between
      marginal food secure families from food secure families among non-poor
      households. Connecting food assistance programs with established social services
      may decrease the negative impact that cumulative family-level risk factors have
      on families' varying levels of food insecurity. 

PMID- 25592938
TI  - The often overlooked issue of statistical power: this and other issues regarding
      assessing importance weighting in quality of life measures.
AB  - In the area of quality of life research, researchers may ask respondents to rate
      importance as well as satisfaction of various life domains (such as job and
      health) and use importance ratings as weights to calculate overall, or global,
      life satisfaction. The practice of giving more important domains more weight,
      known as importance weighting, has not been without controversy. Several previous
      studies assessed importance weighting using the analytical approach of moderated
      regression. This study discusses major issues related to how importance weighting
      has been assessed. Specifically, this study highlights that studies on importance
      weighting without considering statistical power are prone to type II error, i.e.,
      failing to reject the null hypothesis of no significant weighting effect when the
      null hypothesis is actually false. The sample size required for adequate
      statistical power to detect importance weighting functions appeared larger than
      most previous studies could offer. 

PMID- 25592939
TI  - Work-family conflict in context: the impact of structural and perceived
      neighborhood disadvantage on work-family conflict.
AB  - Despite increasing levels of work-family conflict (WFC) among North Americans,
      few scholars examine the broader contexts in which these conflicts occur. I
      address this gap by examining how the neighborhood of residence impacts WFC, with
      a focus on social inequality and disadvantage across neighborhoods. I hypothesize
      that neighborhood disadvantage may impact WFC directly-by introducing ambient
      stressors that inhibit individuals from successfully balancing competing domain
      demands, and indirectly-by undermining the psychological resources that would
      combat the harmful effects of disadvantaged contexts. Using individual and census
      level data from Canada, I consider both objective and subjective measures of
      neighborhood disadvantage and find that, overall, individuals in more
      disadvantaged neighborhoods are worse off because these contexts increase WFC,
      while reducing the psychological resources that would otherwise buffer these
      deleterious effects. However, some of these associations vary by gender. I
      discuss the broader implications of these findings for neighborhood effects and
      WFC research. 

PMID- 25592940
TI  - Gender, trust and cooperation in environmental social dilemmas.
AB  - This research addresses gender differences in environmental protection efforts.
      Recent work indicates that, across a variety of domains, women are more generous,
      charitable, and prosocial than men. Despite above-average levels of these
      motivators for cooperation, considerable experimental research points to no
      difference in cooperation between genders. What can explain women's lower-than
      expected cooperation levels? Prior research indicates that, compared to men,
      women are less trusting and respond to fear incentives in social dilemmas - they
      are concerned about being exploited. We test these arguments in the context of
      environmental behaviors and argue that lower trust and greater responses to fear
      incentives mean that women's cooperation is predicated on trust. For men, trust
      does not predict environmental cooperation. The current research represents the
      first empirical test of these arguments. Using data from the General Social
      Survey we focus on private sphere behaviors and political participation and
      predict an interaction between gender and trust on cooperation. Results support
      this prediction. 

PMID- 25592941
TI  - Growth curve analyses of the relationship between early maternal age and
      children's mathematics and reading performance.
AB  - Regarding the methods used to examine the early maternal age-child academic
      outcomes relationship, the extant literature has tended to examine change using
      statistical analyses that fail to appreciate that individuals vary in their rates
      of growth. Of the one study I have been able to find that employs a true growth
      model to estimate this relationship, the authors only controlled for
      characteristics of the maternal household after family formation; confounding
      background factors of mothers that might select them into early childbearing, a
      possible source of bias, were ignored. The authors' findings nonetheless
      suggested an inverse relationship between early maternal age, i.e., a first birth
      between the ages of 13 and 17, and Canadian adolescents' mean math performance at
      age 10. Early maternal age was not related to the linear slope of age. To
      elucidate whether the early maternal age-child academic outcomes association,
      treated in a growth context, is consistent with this finding, the present study
      built on it using US data and explored children's mathematics and reading
      trajectories from age 5 on. Its unique contribution is that it further explicitly
      controlled for maternal background factors and employed a three-level growth
      model with repeated measures of children nested within their mothers. Though the
      strength of the relationship varied between mean initial academic performance and
      mean academic growth, results confirmed that early maternal age was negatively
      related to children's mathematics and reading achievement, net of post-teen first
      birth child-specific and maternal household factors. Once maternal background
      factors were included, there was no statistically significant relationship
      between early maternal age and either children's mean initial mathematics and
      reading scores or their mean mathematics and reading growth. 

PMID- 25592942
TI  - Extracurricular associations and college enrollment.
AB  - There is consistent evidence that student involvement in extracurricular
      activities (EAs) is associated with numerous academic benefits, yet understanding
      how peer associations within EAs might influence this link is not well
      understood. Using Add Health's comprehensive data on EA participation across 80
      schools in the United States, we develop a novel measure of peer associations
      within EA activities. We find that EA participation with high achieving peers has
      a nontrivial link to college enrollment, even after considering individual, peer,
      and school-level factors. This suggests that school policies aimed at encouraging
      student exposure to high achieving peers in EAs could have an important impact on
      a student's later educational outcomes. 

PMID- 25592943
TI  - Instrumental variables estimates of peer effects in social networks.
AB  - Estimating peer effects with observational data is very difficult because of
      contextual confounding, peer selection, simultaneity bias, and measurement error,
      etc. In this paper, I show that instrumental variables (IVs) can help to address
      these problems in order to provide causal estimates of peer effects. Based on
      data collected from over 4000 students in six middle schools in China, I use the
      IV methods to estimate peer effects on smoking. My design-based IV approach
      differs from previous ones in that it helps to construct potentially strong IVs
      and to directly test possible violation of exogeneity of the IVs. I show that
      measurement error in smoking can lead to both under- and imprecise estimations of
      peer effects. Based on a refined measure of smoking, I find consistent evidence
      for peer effects on smoking. If a student's best friend smoked within the past 30
      days, the student was about one fifth (as indicated by the OLS estimate) or 40
      percentage points (as indicated by the IV estimate) more likely to smoke in the
      same time period. The findings are robust to a variety of robustness checks. I
      also show that sharing cigarettes may be a mechanism for peer effects on smoking.
      A 10% increase in the number of cigarettes smoked by a student's best friend is
      associated with about 4% increase in the number of cigarettes smoked by the
      student in the same time period.

PMID- 25592944
TI  - Phytotherapy - new developments and insights into practice.

PMID- 25592945
TI  - [Obituary Malte Buhring - 18. September 2014].

PMID- 25592946
TI  - Efficacy and safety of Huxin formula in patients after CABG: a multicenter,
      double-blind, randomized clinical trial.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is widely used in the
      treatment of coronary artery disease. A multicenter, double-blind, randomized,
      controlled clinical trial was designed to evaluate the efficacy and safety of
      Huxin Formula post CABG. PATIENTS AND METHODS: 270 inpatients with coronary heart
      disease participated in this study. CABG patients in the control group were
      treated with placebo, while patients in the experimental group were treated with
      Huxin Formula 1 week after the surgery. All patients were treated for 6 months
      and followed up for another 6 months. The main outcomes (death, nonfatal
      myocardial infarction, repeat revascularization, and readmission) were assessed
      360 days after treatment, and secondary outcomes (frequency and scores of angina
      pectoris, etc.) were assessed 0, 90, 180, 270, and 360 days after treatment.
      RESULTS: Our results showed no significant difference between the 2 groups for
      the primary endpoints. In patients with cardiac function class II (New York Heart
      Association), the score of angina pectoris was significantly lower (3.88 +/- 3.86
      vs. 5.45 +/- 3.59) and the frequency of angina pectoris attacks was less (0.96 +/
      1.01 vs. 1.36 +/- 0.94) after 90 days of treatment with Huxin Formula compared
      to placebo (p < 0.05). In patients with 3 coronary vessel lesions, the cardiac
      function class (1.14 +/- 0.35 vs. 1.05 +/- 0.21) after 360 days was significantly
      higher in the control group compared to the treatment group (p < 0.05). There
      were no obvious adverse reactions. CONCLUSION: Huxin Formula may improve cardiac
      function of patients with 3 coronary vessel lesions and relieve symptoms of
      patients with cardiac function class II but failed to show superiority in primary
      outcomes.

PMID- 25592947
TI  - Effect of Panax notoginseng in patients with multiple fractured ribs and
      pulmonary contusions caused by the 2008 Wenchuan earthquake.
AB  - BACKGROUND: The aim of this study was to investigate whether the combination of
      conventional treatment and Panax notoginseng (PN group) is superior to
      conventional treatment alone (CG group) in reducing the clinical symptoms of
      patients with multiple fractured ribs and pulmonary contusions. PATIENTS AND
      METHODS: We retrospectively analyzed the medical records of patients treated for
      multiple fractured ribs and pulmonary contusions with either conventional
      treatment (n = 17) or P. notoginseng (n = 18). Visual analog scale (VAS) pain
      scores and arterial oxygen saturation were measured at baseline and at 1 and 2
      weeks following treatment. The duration of mechanical ventilation, systemic
      analgesics, and hospital stay were also recorded. RESULTS: VAS scores in the PN
      group were lower than in the CG group at 1 week (p < 0.01) and at 2 weeks (p <
      0.05). Arterial oxygen saturation in both groups was higher after treatment than
      at baseline (p < 0.05), but there was no statistically significant difference
      between the 2 groups (p > 0.05). The duration of mechanical ventilation, systemic
      analgesics administration, and hospital stay in the PN group was remarkably
      decreased as compared to the CG group (p < 0.05). CONCLUSION: Combining
      conventional treatment and P. notoginseng seems to be an efficient method that
      can improve the clinical symptoms of multiple fractured ribs and pulmonary
      contusions.

PMID- 25592948
TI  - [Mesembryanthemum crystallinum L. as dermatologically effective medicinal plant -
      first results from 3 pilot studies].
AB  - BACKGROUND: Apart from well-known medical plants of rational phytotherapy there
      is a variety of plants, such as Mesembryanthemum crystallinum L., whose potential
      effects are not examined sufficiently to date. Therefore, in 3 pilot studies we
      investigated the dermatological effect of an extract of M. crystallinum (Mesem
      Cream). MATERIALS AND METHODS: In a retrospective user survey and a pre-post
      study with 6 persons in a wheelchair the efficacy profile of Mesem Cream was
      investigated. In a third placebo-controlled pilot study changes in skin hydration
      was measured using corneometer measurement in 6 healthy volunteers with dry skin.
      RESULTS: Compared to untreated skin, corneometer measurement revealed a
      significant increase of skin hydration with Mesem Cream (25.8 +/- 5.8 pre to 46.6
      +/- 9.2 post treatment vs. 26.3 +/- 6.0 pre to 33.8 +/- 6.0 post treatment) as
      well as a statistical trend (p=0.11; t-Test) compared to basic cream (25.1 +/-
      4.7 pre to 41.9 +/- 7.3 post treatment). Improvement in skin hydration was also
      found in 17 of 29 survey participants. Further, the volunteers in the wheelchair
      showed significant improvements in their subjectively rated skin softness and
      hydration level. CONCLUSION: These pilot studies investigated skin hydrating
      effects of the traditional medical plant M. crystallinum. Although the results
      were promising, they have to be interpreted with caution in particular due to low
      sample size. Further, study design should be more clear-cut and focus skin
      hydration as a main outcome parameter in more detail.

PMID- 25592950
TI  - [Phytotherapy in the German Medical AWMF S3 guidelines - a systematic overview].
AB  - In Germany, the interdisciplinary, evidence- and consensus-based medical AWMF S3
      guidelines represent the highest available scientific level and have significant
      impact on patient care. In Germany, Austria, and Switzerland, herbal medicine has
      a long tradition in medical care. Of notice, the evidence for its efficacy in
      numerous indications is increasing. This systematic review evaluates to which
      extent phytotherapy is taken into account in the current S3 guidelines. In all
      available medical AWMF S3 guidelines, the recommendations/statements on
      phytotherapeutic options were identified, and 2 independent experts classified
      them into 3 categories: positive, negative, and open. In addition, comments on
      side effects and interactions were extracted. Phytotherapeutic options are
      specified in 40 (31.3 %) out of 128 AWMF S3 guidelines. Phytotherapy was not
      included in 55 guidelines (42.9%) with potential herbal therapeutic options. From
      204 recommendations 139 (68.1%) are negative or remain open. In 27 guidelines
      (67.5%) phytotherapy is listed in the chapter for complementary and alternative
      medicine and/or miscellaneous, in 7 guidelines (17.5%) it is mentioned at the end
      of the recommendations on medical drug therapy, and in 8 guidelines (20.0%) it is
      listed in the recommendations regarding conventional treatments. Side effects and
      interactions are stated in 70 out of 204 recommendations (34.3%). Less than half
      of the currently available medical AWMF S3 guidelines include phytotherapy in
      their search strategy. Only few positive statements and recommendations on herbal
      medicine are taken into account. A systematic and comprehensive work up of the
      existing evidence on the one hand and the consequent incorporation on the other
      is necessary to appropriately integrate phytotherapy in the German medical
      guidelines.

PMID- 25592949
TI  - Treatment of organic livestock with medicinal plants: a systematic review of
      European ethnoveterinary research.
AB  - BACKGROUND: The EC Regulation for Organic Farming states that organic livestock
      should be treated preferably with phytotherapeutic products. In spite of the high
      importance of organic livestock in Europe, primarily ruminants, today almost no
      phytotherapeutic product is registered for livestock. Also, information regarding
      veterinary phytotherapy is rare. The aim of this paper is to find approaches to
      cope with health problems of organic ruminants in Europe on the basis of findings
      from the European ethnoveterinary medicine (EuEVM). METHODS: A systematic review
      of ethno-biomedicinal papers was conducted with the aid of the Scopus database,
      and 75 papers, from European countries were analyzed regarding ethnoveterinary
      information. RESULTS: A total of 590 plant species referring to 102 different
      plant families are reported to be used for animal treatment, with Asteraceae,
      Fabaceae and Lamiaceae being the most important families. The traditional use of
      some plant species (e.g. mallow, chamomile, wormwood) corresponds with findings
      from recent scientific literature. The large number of less studied plant
      species, such as white lupin as an antiparasitic herb, and Helleborus spp. as
      potential immunostimulatory agent, opens an interesting field for future
      research. CONCLUSIONS: In general, EuEVM provides interesting treatment
      approaches for gastrointestinal and dermatological disorders as well as
      parasitosis. Findings regarding disorders of female genital or respiratory tract
      are less consistent. Nevertheless, EuEVM offers a solid basis for stimulating
      research in veterinary phytotherapy in Europe with a perspective to solve animal
      health problems in organic or even nonorganic ruminant production.

PMID- 25592951
TI  - [Quality and safety of Chinese medicine drugs in Germany - an update].
AB  - BACKGROUND: In the past, traditional Chinese medicine (TCM) drugs (TCD) had in
      part severe shortcomings regarding quality and safety. The current state of
      knowledge in this field was evaluated. MATERIAL AND METHODS: Expert interviews by
      using standardized questionnaires, systematic literature research of studies from
      Germany published in 1998-2013, systematic inquiries to surveillance authorities
      and information centers for intoxications as well as investigation of
      certificates of analysis of the TCM granulate 'Tianwang buxin dan' from 8
      available sources in Germany and analyses of its content of lead, cadmium, and
      mercury. RESULTS: Current quality and safety risks comprise self-medication, TCM
      unexperienced pharmacies, Internet sale and granulates. 11 studies published
      between 1998 and 2008 evaluated the quality and safety of TCD in Germany. Also in
      newer studies, the values found for heavy metals, pesticides, and microbiological
      contaminants of TCD in part exceeded the maximum permissible values. 28 reports
      of adverse events were made to the Center for Therapy Safety in Chinese Drug
      Therapy (CTCA) within the years 2004-2012. A definite causality was determined in
      2 cases (allergic reaction, reaction of the circulatory system); 7 of the 28
      reports had a likely causality. 61 of 104 (59%) certificates of 'Tianwang buxin
      dan' from 8 different sources could be obtained. 45 of 61 certificates (74%)
      complied with the requirements according to the pharmacy work rules. Shortcomings
      were, amongst others, lacking analyses (identity, aflatoxines, microbiology,
      pesticides). Critical values were exceeded neither in the certificates nor in the
      analyses arranged by us. CONCLUSION: Shortcomings in quality and safety risks of
      TCD still remain, but must be further distinguished. Reports of adverse events
      are very rare.

PMID- 25592952
TI  - An approach to the concept of tonic: suggested definitions and historical
      aspects.
AB  - In traditional medicine, especially CAM, the concept of (herbal) tonics has a
      long history in the different medical systems (TEN -- Traditional European
      Naturopathy; TCM - Traditional Chinese Medicine). Nevertheless, the ideas
      concerning the function of a tonic differ, e.g., stimulation of body functions,
      strengthening of organ function, enhancement of adaption, and well-being.
      Although no exact pharmacodynamic or pharmacokinetic properties of tonics can be
      given, the following general definition, even in the transcultural comparison
      between European and Chinese concepts, seems meaningful: A tonic is an agent that
      has the capability to restore and/or maintain the physiological functioning of an
      organ system, leading to the subjective feeling of well-being of the patient
      treated with it.

PMID- 25592953
TI  - Can Glycyrrhiza glabra L. reduce delirium after coronary artery bypass graft
      surgery?

PMID- 25592955
TI  - Hemagglutinin-neuraminidase gene sequence-based reclassification of human
      parainfluenza virus 3 variants.
AB  - The most comprehensive phylogenetic classification of human parainfluenza virus 3
      (HPIV-3) was recently developed [PLoS One 2012;7:e43893]. This classification
      included three distinct clusters (A, B and C) with subdivision of cluster C into
      four subclusters (C1-4). In the present report, the classification of HPIV-3 was
      refined by inclusion of 27 overlooked beside newly characterized Saudi variants.
      The new phylogram was developed and included the same clusters described before,
      in which cluster A remained unchanged and cluster B contained more recent
      isolates. The organization of cluster C was altered through inclusion of a new
      subcluster (C5), subdivision of C1 into two lineages C1a and C1b and subdivision
      of C3 into three lineages C3a, C3b and C3c. The majority of Saudi variants were
      classified as members of subcluster C1b, whereas only one variant was placed in
      each of subclusters C2 and C5. This study illustrates an up-to-date phylogenetic
      classification of HPIV-3 variants.

PMID- 25592956
TI  - Generation of hydrate forms of paroxetine HCl from the amorphous state: an
      evaluation of thermodynamic and experimental predictive approaches.
AB  - In this study, we evaluate the use of theoretical thermodynamic analysis of
      amorphous paroxetine hydrochloride (HCl) as well as experimental assessment in
      order to identify the most promising approach to stability and dissolution
      behaviour prediction, particularly in relation to stoichiometric and
      nonstoichiometric hydrate formation. Differential scanning calorimetry,
      thermogravimetric analysis, Fourier transform infrared and X-ray diffraction
      techniques were used. Parameters including heat capacity, configurational
      thermodynamic quantities, fragility and relaxation time classified amorphous
      paroxetine HCl as a moderate fragile glass with a considerable degree of
      molecular mobility. Solubility studies indicated little advantage of the
      amorphous form over the crystalline due to conversion to the hydrate Form I
      during equilibration, while the dissolution rate was higher for the amorphous
      form under sink conditions. A marked difference in the physical stability of
      amorphous paroxetine HCl was observed between dry and low humidity storage, with
      the system recrystallizing to the hydrate form. We conclude that, in this
      particular case (amorphous conversion to the hydrate), water may be playing a
      dual role in both plasticizing the amorphous form and driving the equilibrium
      towards the hydrate form, hence prediction of recrystallization behaviour from
      amorphous characteristics may be confounded by the additional process of hydrate
      generation.

PMID- 25592957
TI  - A charge neutral, size tuneable polymersome capable of high biological
      encapsulation efficiency and cell permeation.
AB  - The field of therapeutics is evolving to include a greater proportion of higher
      molecular weight, hydrophilic biological compounds. To cater for this new era in
      healthcare the concomitant development of appropriate drug delivery systems is
      essential to aid cellular permeation. In this manuscript we present the
      synthesis, characterisation and biological evaluation of a charge neutral
      polymersome (Ps) based drug delivery system (DDS) using an amphiphilic pegylated
      random copolymer. A detailed dynamic light scattering study revealed that the
      hydrodynamic diameter of the Ps can be tailored to a specific size simply by
      varying the quantities and ratios used during the preparation step. The zeta
      potential of this new drug delivery system was determined to be -0.095 +/- 0.037
      mV, the encapsulation efficiency of Fitc-CM-Dextran (4 KDa) was 70%, the uptake
      of Fitc-CM-Dextran by Hela cells was increased 4-fold when encapsulated within
      the polymersomal system. The facile preparation, high loading capacity and size
      tuneable nature of this Ps renders it a promising alternative to the ever growing
      array of currently available Ps.

PMID- 25592959
TI  - Genome-wide analysis of the WRKY transcription factors in aegilops tauschii.
AB  - The WRKY transcription factors (TFs) play important roles in responding to
      abiotic and biotic stress in plants. However, due to its unfinished genome
      sequencing, relatively few WRKY TFs with full-length coding sequences (CDSs) have
      been identified in wheat. Instead, the Aegilops tauschii genome, which is the D
      genome progenitor of the hexaploid wheat genome, provides important resources for
      the discovery of new genes. In this study, we performed a bioinformatics analysis
      to identify WRKY TFs with full-length CDSs from the A. tauschii genome. A
      detailed evolutionary analysis for all these TFs was conducted, and quantitative
      real-time PCR was carried out to investigate the expression patterns of the
      abiotic stress-related WRKY TFs under different abiotic stress conditions in A.
      tauschii seedlings. A total of 93 WRKY TFs were identified from A. tauschii, and
      79 of them were found to be newly discovered genes compared with wheat. Gene
      phylogeny, gene structure and chromosome location of the 93 WRKY TFs were fully
      analyzed. These studies provide a global view of the WRKY TFs from A. tauschii
      and a firm foundation for further investigations in both A. tauschii and wheat.

PMID- 25592958
TI  - Working memory and language network dysfunctions in logopenic aphasia: a task
      free fMRI comparison with Alzheimer's dementia.
AB  - We aimed to determine whether network-level functional connectivity differs in 2
      clinical variants of Alzheimer's disease: logopenic primary progressive aphasia
      (lvPPA) and dementia of the Alzheimer's type (DAT). Twenty-four lvPPA subjects
      with amyloid deposition on positron emission tomography and task-free functional
      magnetic resonance imaging were matched to 24 amyloid-positive DAT subjects and
      24 amyloid-negative controls. Independent-component analysis and spatial-temporal
      dual regression were used to assess functional connectivity within the language
      network, left and right working memory networks, and ventral default mode
      network. lvPPA showed reduced connectivity in left temporal language network and
      inferior parietal and prefrontal regions of the left working memory network
      compared with controls and DAT. Both groups showed reduced connectivity in the
      parietal regions of the right working memory network compared with controls. Only
      DAT showed reduced ventral default mode network connectivity compared with
      controls. Aphasia severity correlated with connectivity in the left working
      memory network within lvPPA. Patterns of network dysfunction differ across these
      2 clinical variants of Alzheimer's disease, with lvPPA particularly associated
      with disruptions in the language and left working memory networks. 

PMID- 25592961
TI  - Quinine-catalyzed highly enantioselective cycloannulation of o-quinone methides
      with malononitrile.
AB  - 2-Amino-3-cyano-4H-chromenes show great potential as novel anticancer agents.
      Here we report a quinine-catalyzed highly enantioselective formal 4 + 2
      cycloaddition of ortho-quinone methides and malononitrile, providing a unique
      approach to 4-arylvinyl, 4-aryl and 4-vinyl 2-amino-3-cyano-4H-chromenes with
      excellent yields and enantioselectivities. Moreover, this reaction can be
      performed in up to 6 mmol scale without any noticeable loss of yield and
      stereoselectivity. 

PMID- 25592960
TI  - Analysis of the ORFK1 hypervariable regions reveal distinct HHV-8 clustering in
      Kaposi's sarcoma and non-Kaposi's cases.
AB  - BACKGROUND: Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which
      develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host
      predisposing factors, viral genetic variants might possibly be related to disease
      development. The aim of this study was to identify HHV-8 variants in patients
      with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated
      cutaneous lymphoproliferative disorders. METHODS: The VR1 and VR2 regions of the
      ORF K1 sequence were analyzed in samples (peripheral blood and/or lesional
      tissue) collected between 2000 and 2010 from 27 subjects with HHV-8 infection,
      established by the presence of anti-HHV-8 antibodies. On the basis of viral
      genotyping, a phylogenetic analysis and a time-scaled evaluation were performed.
      RESULTS: Two main clades of HHV-8, corresponding to A and C subtypes, were
      identified. Moreover, for each subtype, two main clusters were found
      distinctively associated to cKS or non-cKS subjects. Selective pressure analysis
      showed twelve sites of the K1 coding gene (VR1 and VR2 regions) under positive
      selective pressure and one site under negative pressure. CONCLUSION: Thus,
      present data suggest that HHV-8 genetic variants may influence the susceptibility
      to cKS in individuals with HHV-8 infection.

PMID- 25592962
TI  - The intriguing relationship between the ABO blood group, cardiovascular disease,
      and cancer.
AB  - Other than being present at the surface of red blood cells, the antigens of the
      ABO blood group system are efficiently expressed by a variety of human cells and
      tissues. Several studies recently described the involvement of the ABO blood
      group in the pathogenesis of many human disorders, including cardiovascular
      disease and cancer, so that its clinical significance extends now beyond the
      traditional boundaries of transfusion medicine. In a large cohort study recently
      published in BMC Medicine and including over 50,000 subjects, Etemadi and
      colleagues reported that nearly 6% of total deaths and as many as 9% of
      cardiovascular deaths could be attributed to having non-O blood groups, a
      condition that was also found to be associated with increased risk of gastric
      cancer. In this commentary, the clinical implications of ABO blood groups are
      critically discussed and a possible common pathogenic mechanism involving the von
      Willebrand factor is described.

PMID- 25592963
TI  - Are patients admitted to hospitals from care homes dehydrated? A retrospective
      analysis of hypernatraemia and in-hospital mortality.
AB  - OBJECTIVES: To compare risks of hypernatraemia on admission to hospital in
      persons who were with those who were not identified as care home residents and
      evaluate the association of hypernatraemia with in-hospital mortality. DESIGN:
      Retrospective observational study. SETTING: A National Health Service Trust in
      London. PARTICIPANTS: A total of 21,610 patients aged over 65 years whose first
      admission to the Trust was between 1 January 2011 and 31 December 2013. MAIN
      OUTCOME MEASURES: Hypernatraemia on admission (plasma Na > 145 mmol/L) and in
      hospital death. RESULTS: Patients admitted from care homes had 10-fold higher
      prevalence of hypernatraemia than those from their own homes (12.0% versus 1.3%,
      respectively; odds ratio [OR]: 10.5, 95% confidence interval [CI]: 8.43-13.0). Of
      those with hypernatraemia, nine in 10 cases were associated with nursing home
      ECOHOST residency (attributable fraction exposure: 90.5%), and the population
      attributable fraction of hypernatraemia on admission associated with care homes
      was 36.0%. After correcting for age, gender, mode of admission and dementia, care
      home residents were significantly more likely to be admitted with hypernatraemia
      than were own-home residents (adjusted odds ratio [AOR]: 5.32, 95% CI: 3.85
      7.37). Compared with own-home residents, care home residents were also at about a
      two-fold higher risk of in-hospital mortality compared with non-care home
      residents (AOR: 1.97, 95% CI: 1.59-2.45). Consistent with evidence that
      hypernatraemia is implicated in higher mortality, the association of nursing
      homes with in-hospital mortality was attenuated after adjustment for it (AOR:
      1.61, 95% CI: 1.26-2.06). CONCLUSIONS: Patients admitted to hospital from care
      homes are commonly dehydrated on admission and, as a result, appear to experience
      significantly greater risks of in-hospital mortality.

PMID- 25592964
TI  - Trypanosoma rangeli displays a clonal population structure, revealing a
      subdivision of KP1(-) strains and the ancestry of the Amazonian group.
AB  - Assessment of the genetic variability and population structure of Trypanosoma
      rangeli, a non-pathogenic American trypanosome, was carried out through
      microsatellite and single-nucleotide polymorphism analyses. Two approaches were
      used for microsatellite typing: data mining in expressed sequence tag /open
      reading frame expressed sequence tags libraries and PCR-based Isolation of
      Microsatellite Arrays from genomic libraries. All microsatellites found were
      evaluated for their abundance, frequency and usefulness as markers. Genotyping of
      T. rangeli strains and clones was performed for 18 loci amplified by PCR from
      expressed sequence tag/open reading frame expressed sequence tags libraries. The
      presence of single-nucleotide polymorphisms in the nuclear, multi-copy, spliced
      leader gene was assessed in 18 T. rangeli strains, and the results show that T.
      rangeli has a predominantly clonal population structure, allowing a robust
      phylogenetic analysis. Microsatellite typing revealed a subdivision of the KP1(-)
      genetic group, which may be influenced by geographical location and/or by the co
      evolution of parasite and vectors occurring within the same geographical areas.
      The hypothesis of parasite-vector co-evolution was corroborated by single
      nucleotide polymorphism analysis of the spliced leader gene. Taken together, the
      results suggest three T. rangeli groups: (i) the T. rangeli Amazonian group; (ii)
      the T. rangeli KP1(-) group; and (iii) the T. rangeli KP1(+) group. The latter
      two groups possibly evolved from the Amazonian group to produce KP1(+) and KP1(-)
      strains. 

PMID- 25592965
TI  - Estimation of genetic parameters for resistance to gastro-intestinal nematodes in
      pure blood Arabian horses.
AB  - Equine internal parasites, mostly cyathostomins, affect both horse welfare and
      performance. The appearance of anthelmintic-resistant parasites creates a
      pressing need for optimising drenching schemes. This optimization may be achieved
      by identifying genetic markers associated with host susceptibility to infection
      and then to drench carriers of these markers. The aim of our study was to
      characterise the genetics of horse resistance to strongyle infection by
      estimating heritability of this trait in an Arabian pure blood population. A
      population of 789 Arabian pure blood horses from the Michalow stud farm, Poland
      were measured for strongyle egg excretion twice a year, over 8 years. Low
      repeatability values were found for faecal egg counts. Our analyses showed that
      less than 10% of the observed variation for strongyle faecal egg counts in this
      population had a genetic origin. However, additional analyses highlighted an age
      dependent increase in heritability which was 0.04 (+/-0.02) in young horses (up
      to 3 years of age) but 0.21 (+/-0.04) in older ones. These results suggest that a
      significant part of the inter-individual variation has a genetic origin. This
      paves the way to a genomic dissection of horse-nematode interactions which might
      provide predictive markers of susceptibility, allowing individualised drenching
      schemes.

PMID- 25592966
TI  - Effects of photobleaching on selected advanced glycation end products in the
      human lens.
AB  - BACKGROUND: Cataract is the leading cause of blindness, especially in the
      developing world. To ease access to treatment, we have proposed that cataract
      could be treated non-invasively by photobleaching of the chemically modified
      proteins responsible for cataract formation. The present study was aimed at
      examining the optical and biochemical effects of the proposed treatment. METHODS:
      Human donor lenses were photobleaced using a 445 nm cw laser. Lens optical
      quality was assessed before and after photobleaching by light transmission and
      scattering. The concentration of the advanced glycation end products (AGEs)
      pentosidine, argpyrimidine, carboxymethyllysine, hydroimidazolone was measured.
      RESULTS: Transmission increased and AGE-related fluorescence decreased
      significantly after photobleaching but no changes were observed in the
      concentration of the measured AGEs. CONCLUSIONS: We found a significant effect of
      the photobleaching treatment on lens optical parameters but we could not
      associate the optical findings to a change in the concentration of the AGEs we
      measured. This finding suggests that other AGEs were responsible for the observed
      photobleaching of the human lens after laser treatment. The biochemical nature of
      the photochemical reactions associated with photobleaching remains to be
      elucidated.

PMID- 25592967
TI  - Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced
      vascular damages and fenofibrate intervention.
AB  - Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but
      whether its protective effect on endothelium-dependent vasodilatation (EDV) in
      thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown.
      In this study, female Sprauge Dawley rats were divided into standard chow diets
      (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly.
      The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF
      rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months.
      The pathological and tensional changes, protein expression of eNOS, and ER stress
      related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA)
      and FF on EDV of thoracic aorta from normal female SD rats were observed.
      Ultimately the expression of ER stress related genes were assessed in primary
      mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We
      found that FF treatment improved serum lipid levels and pathological changes in
      thoracic aorta, accompanied with decreased ER stress and increased
      phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different
      concentrations of PA treatment. The dose- and time-dependent inhibition of cell
      proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and
      expression of ER stress related genes were all inverted by FA pretreatment in PA
      treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic
      HFD feeding and acute stimulation of PA, this effect is related with decreased ER
      stress and increased phosphorylation of eNOS.

PMID- 25592968
TI  - 17beta-estradiol regulates cell proliferation, colony formation, migration,
      invasion and promotes apoptosis by upregulating miR-9 and thus degrades MALAT-1
      in osteosarcoma cell MG-63 in an estrogen receptor-independent manner.
AB  - In bone, different concentration of estrogen leads to various of physiological
      processes in osteoblast, such as the proliferation, migration, and apoptosis in
      an estrogen receptor-dependent manner. But little was known about the estrogen
      effects on osteosarcoma (OS). In this study, OS cell MG-63 was treated with low
      (1 nM) or high (100 nM) dose of 17beta-Estradiol (E2) with the presence or
      absence of estrogen receptor alpha (ERalpha), for evaluating the E2 effects on
      proliferation, migration, invasion, colony formation and apoptosis. Consistent
      with a previous study, high dose of E2 treatment dramatically downregulated
      expressing level of long non-coding RNA metastasis associated lung adenocarcinoma
      transcript 1 (MALAT-1). The observation of upregulation of miR-9 after a high
      dose of E2 treatment indicated the cause of MALAT-1 reduction. Downregulation of
      MALAT-1 promoted the combination of SFPQ/PTBP2 complex. It was also observed that
      the proliferation, migration, invasion, colony formation and apoptosis of OS
      cells were remarkably affected by high dose of E2 treatment, but not by low dose,
      in an ERalpha independent manner. Furthermore, the abolishment of the effects on
      these physiological processes caused by ectopic expression of miR-9 ASOs
      suggested the necessity of miR-9 in MALAT-1 regulation. Here we found that the
      high dose of E2 treatment upregulated miR-9 thus posttranscriptionally regulated
      MALAT-1 RNA level in OS cells, and then the downregulation of MALAT-1 inhibited
      cell proliferation, migration, invasion and epithelial-mesenchymal transition
      (EMT) processes in the E2-dose dependent and ER-independent ways.

PMID- 25592969
TI  - Nifedipine inhibits ox-LDL-induced lipid accumulation in human blood-derived
      macrophages.
AB  - Studies have shown that nifedipine, an anti-hypertensive drug, protects against
      atherosclerotic progression, but the underlying mechanisms remain elusive.
      Oxidized low-density lipoprotein (ox-LDL) is critically implicated in macrophage
      lipid deposition seen in atherosclerosis. In this study, we examined the effects
      of nifedipine on some ox-LDL-associated changes in human blood-derived
      macrophages. We isolated monocytes from normal human blood and differentiated
      them into macrophages. We then treated these human macrophages with ox-LDL and/or
      nifedipine, and examined lipid accumulation and expression levels of two scavenge
      receptors CD36 and SR-A as well as a protein kinase PKC-theta. Nifedipine
      treatment substantially reduced lipid accumulation and the expression of CD36, SR
      A, and protein kinase C (PKC)-theta in human macrophages treated with ox-LDL.
      Silencing of PKC-theta using siRNA also reduced the expression of CD36 and SR-A
      in these cells. Our results thus suggest that nifedipine may inhibit
      atherosclerosis by reducing ox-LDL-induced lipid deposition through suppression
      of the CD36/SR-A-mediated uptake of ox-LDL by macrophages via a PKC-theta
      dependent mechanism. 

PMID- 25592970
TI  - The WNT inhibitor APCDD1 sustains the expression of beta-catenin during the
      osteogenic differentiation of human dental follicle cells.
AB  - In hair follicle cells APCDD1 inhibits the canonical WNT/beta-Catenin pathway and
      its inactivation is associated with an autosomal dominant form of hair loss. We
      analyzed the role of APCDD1 for the osteogenic differentiation in dental follicle
      cells (DFCs) and identified a new and surprising function. Contrarily to hair
      follicle cells APCDD1 was crucial for the expression of beta-Catenin and for the
      activity of the TCF/LEF reporter assay in DFCs. In addition, a depletion of
      APCDD1 inhibits the expression of osteogenic markers such as RUNX2 and decreased
      the matrix mineralization. However, similar to hair follicle cells in previous
      studies a control cell culture with oral squamous carcinoma cells showed that
      APCDD1 inhibits the expression of beta-Catenin and of typical target genes of the
      canonical WNT/beta-Catenin pathway. In conclusion, our data disclosed an unusual
      role of APCDD1 in DFCs during the osteogenic differentiation. APCDD1 sustains the
      expression and activation of beta-Catenin. 

PMID- 25592971
TI  - Redox sensor proteins for highly sensitive direct imaging of intracellular redox
      state.
AB  - Intracellular redox state is a critical factor for fundamental cellular
      functions, including regulation of the activities of various metabolic enzymes as
      well as ROS production and elimination. Genetically-encoded fluorescent redox
      sensors, such as roGFP (Hanson, G. T., et al. (2004)) and Redoxfluor (Yano, T.,
      et al. (2010)), have been developed to investigate the redox state of living
      cells. However, these sensors are not useful in cells that contain, for example,
      other colored pigments. We therefore intended to obtain simpler redox sensor
      proteins, and have developed oxidation-sensitive fluorescent proteins called Oba
      Q (oxidation balance sensed quenching) proteins. Our sensor proteins derived from
      CFP and Sirius can be used to monitor the intracellular redox state as their
      fluorescence is drastically quenched upon oxidation. These blue-shifted spectra
      of the Oba-Q proteins enable us to monitor various redox states in conjunction
      with other sensor proteins.

PMID- 25592973
TI  - Subfertility and assisted reproduction techniques are associated with poorer
      cardiometabolic profiles in childhood.
AB  - The effects of artificial reproductive techniques and subfertility on
      cardiovascular and metabolic profiles of children aged 5-6 years were
      investigated using data from the Amsterdam Born Children and their Development
      study. Of the 2577 children, 34 were conceived through ovulation induction, 51
      through artificial insemination and 28 through IVF or intracytoplasmic sperm
      injection (ICSI). Two hundred and twenty children were born to couples who
      conceived after more than 12 months and 2244 were born to couples who conceived
      within 12 months of unprotected intercourse ('subfertile' and 'fertile',
      respectively). At the age of 5-6 years, fasting glucose levels were higher among
      children conceived through ovulation induction and IVF-ICSI compared with those
      of children of fertile couples (adjusted difference: ovulation induction: 0.4
      mmol/l, 95% CI 0.2 to 0.6; IVF-ICSI: 0.2 mmol/l, 95% CI 0.0 to 0.5). Blood
      pressure was higher in children of subfertile couples compared with that of
      children of fertile couples (adjusted difference systolic blood pressure: 0.8
      mmHg, 95% CI -0.2 to 1.8; diastolic blood pressure: 1.4 mmHg, 95% CI 0.6 to 2.3).
      Subfertility and conception through ovulation induction and IVF-ICSI each
      contributed to aspects of an adverse cardiovascular and metabolic profile in
      childhood.

PMID- 25592972
TI  - An aberrant sugar modification of BACE1 blocks its lysosomal targeting in
      Alzheimer's disease.
AB  - The beta-site amyloid precursor protein cleaving enzyme-1 (BACE1), an essential
      protease for the generation of amyloid-beta (Abeta) peptide, is a major drug
      target for Alzheimer's disease (AD). However, there is a concern that inhibiting
      BACE1 could also affect several physiological functions. Here, we show that BACE1
      is modified with bisecting N-acetylglucosamine (GlcNAc), a sugar modification
      highly expressed in brain, and demonstrate that AD patients have higher levels of
      bisecting GlcNAc on BACE1. Analysis of knockout mice lacking the biosynthetic
      enzyme for bisecting GlcNAc, GnT-III (Mgat3), revealed that cleavage of Abeta
      precursor protein (APP) by BACE1 is reduced in these mice, resulting in a
      decrease in Abeta plaques and improved cognitive function. The lack of this
      modification directs BACE1 to late endosomes/lysosomes where it is less
      colocalized with APP, leading to accelerated lysosomal degradation. Notably,
      other BACE1 substrates, CHL1 and contactin-2, are normally cleaved in GnT-III
      deficient mice, suggesting that the effect of bisecting GlcNAc on BACE1 is
      selective to APP. Considering that GnT-III-deficient mice remain healthy, GnT-III
      may be a novel and promising drug target for AD therapeutics. 

PMID- 25592974
TI  - Successful pregnancy and delivery after ICSI with artificial oocyte activation by
      calcium ionophore in in-vitro matured oocytes: a case report.
AB  - The achievement of a successful pregnancy and delivery after oocyte activation
      with calcium ionophore is reported in a couple having low fertilization rates
      after intracytoplasmic sperm injection (ICSI) of in-vitro matured oocytes. A
      couple, in which the wife had polycystic ovary syndrome and the husband had
      moderate oligoteratozoospermia, showed a low fertilization rate in a previous in
      vitro maturation cycle (2/11 [18.2%]). The most likely cause of complete
      fertilization failure or low fertilization rates is failure of oocyte activation.
      Therefore, artificial oocyte activation by calcium ionophore was combined with
      ICSI to achieve viable fertilized oocytes. Oocytes were stimulated with calcium
      ionophore for 30 min after ICSI. The fertilization rate of oocytes activated with
      calcium ionophore (13/15 [86.7%] and 7/9 [77.8%]) was higher than that of the non
      activated oocytes. In the latest cycle, three embryos derived from the activated
      oocytes were transferred into the uterus on day 3. Subsequently, two gestational
      sacs were identified on ultrasound. The patient delivered dizygotic twins (girl
      2260 g and boy 2760 g) at 35 weeks and 6 days gestation by caesarean section.
      This result suggests that calcium ionophore could be useful for oocyte
      fertilization in couples with low fertilization rates after ICSI of in-vitro
      matured oocytes. 

PMID- 25592975
TI  - Implantation of fresh and thawed-warmed embryos in single embryo transfer cycles:
      interpreting the initial beta-HCG.
AB  - Little is known about the effects of human embryo cryopreservation on
      developmental potential. Initial beta-HCG, indicating embryo implantation, was
      measured in 322 single embryo transfer cycles (246 fresh and 76 thawed-warmed).
      Median initial beta-HCG was higher for fresh compared with thawed-warmed
      transfers (126 versus 100 mIU/ml; P = 0.04). Blastocyst slow cooling resulted in
      a lower initial beta-HCG compared with vitrification (P = 0.01). Live birth rates
      were lower for blastocyst slow cooling (25%) compared with vitrification (71%)
      and fresh transfer (70%). We conclude that cryopreservation may impair an
      embryo's ability to produce beta-HCG, but that vitrification does not impair
      developmental potential. 

PMID- 25592976
TI  - Extreme convergence in egg-laying strategy across insect orders.
AB  - The eggs of stick and leaf insects (Phasmatodea) bear strong resemblance to plant
      seeds and are commonly dispersed by females dropping them to the litter. Here we
      report a novel egg-deposition mode for Phasmatodea performed by an undescribed
      Vietnamese species of the enigmatic subfamily Korinninae that produces a complex
      egg case (ootheca), containing numerous eggs in a highly ordered arrangement.
      This novel egg-deposition mode is most reminiscent of egg cases produced by
      members of unrelated insect orders, e.g. by praying mantises (Mantodea) and
      tortoise beetles (Coleoptera: Cassidinae). Ootheca production constitutes a
      striking convergence and major transition in reproductive strategy among stick
      insects, viz. a shift from dispersal of individual eggs to elaborate egg
      concentration. Adaptive advantages of ootheca formation on arboreal substrate are
      likely related to protection against parasitoids and desiccation and to
      allocation of specific host plants. Our phylogenetic analysis of nuclear (28S,
      H3) and mitochondrial (COI, COII) genes recovered Korinninae as a subordinate
      taxon among the species-rich Necrosciinae with Asceles as sister taxon, thus
      suggesting that placement of single eggs on leaves by host plant specialists
      might be the evolutionary precursor of ootheca formation within stick insects. 

PMID- 25592977
TI  - Changes in brain-derived neurotrophic factor (BDNF) during abstinence could be
      associated with relapse in cocaine-dependent patients.
AB  - Brain-derived neurotrophic factor (BDNF) is involved in cocaine craving in humans
      and drug seeking in rodents. Based on this, the aim of this study was to explore
      the possible role of serum BDNF in cocaine relapse in abstinent addicts. Forty
      cocaine dependent subjects (DSM-IV criteria) were included in an inpatient 2
      weeks abstinence program. Organic and psychiatric co-morbidities were excluded.
      Two serum samples were collected for each subject at baseline and at after 14
      abstinence days. After discharge, all cocaine addicts underwent a 22 weeks follow
      up, after which they were classified into early relapsers (ER) (resumed during
      the first 14 days after discharge,) or late relapsers (LR) (resumed beyond 14
      days after discharge). The only clinical differences between groups were the
      number of consumption days during the last month before detoxification. Serum
      BDNF levels increased significantly across the 12 days of abstinence in the LR
      group (p=0.02), whereas in the ER group BDNF remained unchanged. In the ER group,
      the change of serum BDNF during abstinence negatively correlated with the
      improvement in depressive symptoms (p=0.02). These results suggest that BDNF has
      a role in relapse to cocaine consumption in abstinent addicts, although the
      underlying neurobiological mechanisms remain to be clarified. 

PMID- 25592978
TI  - Cognitive functioning after deep brain stimulation in subcallosal cingulate gyrus
      for treatment-resistant depression: an exploratory study.
AB  - Deep brain stimulation (DBS) is being investigated as a therapeutic alternative
      for patients with treatment-resistant depression (TRD), but its cognitive safety
      has been scarcely explored. The aim of this exploratory study is to evaluate
      cognitive function of patients before and after deep brain stimulation of the
      subgenual cingulate gyrus (SCG). Eight treatment-resistant depressed patients
      were implanted in subgenual cingulate gyrus. A neuropsychological battery was
      used to evaluate patients before surgery and 1-year after. A matched group of
      eight first-episode patients was also assessed. A MANOVA was performed for each
      cognitive domain and those tests showing main time effects were then correlated
      with depressive symptoms and with medication load. There were significant group
      and time effects for memory and a group effect for language. No significant
      interactions between groups or cognitive domains were observed. Medication load
      was negatively correlated with memory at time 1, and clinical change negatively
      correlated with memory improvement. These findings support the cognitive safety
      of DBS of subgenual cingulate gyrus, as cognitive function did not worsen after
      chronic stimulation and memory performance even improved. The results, though,
      should be interpreted cautiously given the small sample size and the fact that
      some treatment-resistant patients received electroconvulsive therapy (ECT) before
      implantation. 

PMID- 25592979
TI  - Frequency and functions of non-suicidal self-injury: associations with suicidal
      thoughts and behaviors.
AB  - Previous research has found associations between non-suicidal self-injury (NSSI)
      and suicidal thoughts and behaviors (STBs), yet the nature of this relationship
      remains equivocal. The goal of the present study was to examine how lifetime NSSI
      frequency and individual NSSI functions relate to a history of suicidal ideation,
      plan, and attempt. Data were collected via a large (N=13,396) web-based survey of
      university students between the ages of 18 and 29. After demographics and
      psychiatric conditions were controlled for, we found a positive curvilinear
      relationship between NSSI frequency and each of the suicide outcomes. When
      examined among those with STBs, bipolar disorder and problematic substance use
      remained positively associated with risk for suicide attempt, but not NSSI.
      Analyses of individual NSSI functions showed differential associations with STBs
      of varying severity. Specifically, nearly every NSSI function was significantly
      related to suicide attempt, with functions related to avoiding committing
      suicide, coping with self-hatred, and feeling generation (anti-dissociation)
      showing the strongest risks for suicide attempt. From both clinical and research
      perspectives, these findings suggest the importance of assessing multiple reasons
      for engaging in self-injury. 

PMID- 25592980
TI  - Interpolating gain-scheduled Hinfinity loop shaping design for high speed ball
      screw feed drives.
AB  - This paper presents a method to design servo controllers for flexible ball screw
      drives with time-varying dynamics, which are mainly due to the time-varying table
      position and the workpiece mass. A gain-scheduled Hinfinity loop shaping
      controller is designed to achieve high tracking performance against the dynamic
      variations. Hinfinity loop shaping design procedure incorporates open loop
      shaping by a set of compensators to obtain performance/robust stability
      tradeoffs. The interpolating gain-scheduled controller is obtained by
      interpolating the state space model of the linear time-invariant (LTI)
      controllers estimated for fixed values of the scheduling parameters and a linear
      least squares problem can be solved. The proposed controller has been compared
      with P/PI with velocity and acceleration feedforward and adaptive backstepping
      sliding mode control experimentally. The experimental results indicate that the
      tracking performance has been improved and the robustness for time-varying
      dynamics has been achieved with the proposed scheme. 

PMID- 25592981
TI  - Cognitive benefits of right-handedness: a meta-analysis.
AB  - Hand preference - which is related to cerebral dominance - is thought to be
      associated with cognitive skills; however, findings on this association are
      inconsistent and there is no consensus whether left- or right-handers have an
      advantage in either spatial or verbal abilities. In addition, it is not clear
      whether an interaction between sex and hand preference exists in relation to
      these cognitive abilities. As these matters are relevant from a
      neurodevelopmental perspective we performed a meta-analysis of the available
      literature. We searched PubMed and Embase, and included 14 studies (359,890
      subjects) in the verbal ability meta-analysis and 16 studies (218,351 subjects)
      in the spatial ability meta-analysis. There was no difference between the full
      sample of left and right-handers for verbal ability, nor was there a hand
      preference-by-sex interaction. Subgroup analysis of children showed a small right
      hand benefit. Our results further revealed a modest but significant effect
      favouring right-handedness for overall spatial ability, which was more pronounced
      when analysis was restricted to studies applying the mental rotation test. We
      could not identify a specific interaction with sex. Our results indicate that
      there is a small but significant cognitive advantage of right-handedness on
      spatial ability. In the verbal domain, this advantage is only significant in
      children. An interaction effect with sex is not confirmed. 

PMID- 25592982
TI  - Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis
      patients.
AB  - BACKGROUND: CD28(neg) T cells, which display functional characteristic of
      oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be
      pathologically relevant in rheumatoid arthritis manifestation. The CD28 co
      stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell
      populations in these patients. METHODS: Samples were obtained before and after 12
      months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were
      evaluated by flow cytometry and complementarity-determining region-3
      spectratyping, respectively, while telomerase reverse-transcriptase gene level
      was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the
      percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell
      repertoire restrictions; these features are directly correlated. Thymic output
      and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept
      induced decrease of peripheral T-cell repertoire restrictions can due to a
      reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells.

PMID- 25592983
TI  - Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-gamma
      receptor deficiency.

PMID- 25592984
TI  - Diagnostic and experimental food challenges in patients with nonimmediate
      reactions to food.

PMID- 25592985
TI  - Genetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity
      and airway expression of YKL-40.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1
      (CHI3L1) promoter, the gene encoding YKL-40, are associated with circulating YKL
      40 levels and asthma prevalence. However, the effects of gene polymorphisms on
      asthma severity and airway expression of YKL-40 have not been examined.
      OBJECTIVE: We sought to determine the effect of genetic variation in CHI3L1 on
      asthma severity and YKL-40 expression in subjects from the Yale Center for Asthma
      and Airways Disease and the Severe Asthma Research Program. METHODS: SNPs
      spanning the CHI3L1 gene were genotyped in 259 Yale Center for Asthma and Airways
      Disease and 919 Severe Asthma Research Program subjects. Association and
      haplotype analyses were conducted to identify effects on airflow obstruction, YKL
      40 levels, and asthma severity. RESULTS: Fifteen SNPs in CHI3L1 were associated
      with FEV1, serum YKL-40 levels, or both. rs12141494 (intron 6) was the only SNP
      in subjects of European ancestry in both cohorts that was associated with serum
      YKL-40 levels and postbronchodilator FEV1. Conditional analysis demonstrated that
      the effect on lung function was independent of the promoter SNP rs4950928, and
      haplotype analysis demonstrated that G alleles at rs12141494 and rs4950928 are
      associated with lower YKL-40 expression and higher FEV1 percent predicted values.
      In asthmatic subjects the risk allele A at rs12141494 was associated with severe
      asthma and higher YKL-40 expression in the airway (P <= .05). CONCLUSION: In
      contrast to the promoter SNP rs4950928, the intronic SNP rs12141494 in CHI3L1 is
      associated with asthma severity, lung function, and YKL-40 expression in the
      blood and airway. These data suggest that SNP rs12141494 modulates YKL-40
      expression in the airway and contributes to airway remodeling and asthma
      severity.

PMID- 25592987
TI  - Administration of a probiotic with peanut oral immunotherapy: A randomized trial.
AB  - BACKGROUND: Coadministration of a bacterial adjuvant with oral immunotherapy
      (OIT) has been suggested as a potential treatment for food allergy. OBJECTIVE: To
      evaluate a combined therapy comprising a probiotic together with peanut OIT.
      METHODS: We performed a double-blind, placebo-controlled randomized trial of the
      probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT (probiotic and
      peanut oral immunotherapy [PPOIT]) in children (1-10 years) with peanut allergy.
      The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks
      after discontinuation of treatment (referred to as possible sustained
      unresponsiveness). Secondary outcomes were desensitization, peanut skin prick
      test, and specific IgE and specific IgG4 measurements. RESULTS: Sixty-two
      children were randomized and stratified by age (<=5 and >5 years) and peanut skin
      test wheal size (<=10 and >10 mm); 56 reached the trial's end. Baseline
      demographics were similar across groups. Possible sustained unresponsiveness was
      achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P < .001). Nine
      children need to be treated for 7 to achieve sustained unresponsiveness (number
      needed to treat, 1.27; 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT
      and 7.1% receiving placebo were desensitized (P < .001). PPOIT was associated
      with reduced peanut skin prick test responses and peanut-specific IgE levels and
      increased peanut-specific IgG4 levels (all P < .001). PPOIT-treated participants
      reported a greater number of adverse events, mostly with maintenance home dosing.
      CONCLUSION: This is the first randomized placebo-controlled trial evaluating the
      novel coadministration of a probiotic and peanut OIT and assessing sustained
      unresponsiveness in children with peanut allergy. PPOIT was effective in inducing
      possible sustained unresponsiveness and immune changes that suggest modulation of
      the peanut-specific immune response. Further work is required to confirm
      sustained unresponsiveness after a longer period of secondary peanut elimination
      and to clarify the relative contributions of probiotics versus OIT.

PMID- 25592988
TI  - Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
      Interpretation Criteria for Assessment of Antibiotic Treatment Response in
      Pyogenic Spine Infection.
AB  - PURPOSE: The objective of the study was to determine if fluorodeoxyglucose
      positron emission tomography/computed tomography ((18)F-FDG PET/CT) can assess
      the response of patients with pyogenic spine infection to antibiotic treatment in
      a clinically useful time frame. METHODS: Twenty-eight patients with suspected
      pyogenic spine infection had baseline (18)F-FDG PET/CT. Patients with proven or
      probable infection were divided into good and poor responders to antibiotic
      therapy based on clinical criteria. These patients had a follow-up (18)F-FDG
      PET/CT 6-8 weeks later. RESULTS: Six of 28 patients were deemed negative for
      infection based on (18)F-FDG PET/CT. Two patients were excluded because of
      discrepancies in interpretation. Of the 20 patients deemed positive for
      infection, 13 had a pathogen isolated and all showed (18)F-FDG uptake in bone
      and/or soft tissue at baseline. Patients with a poor clinical response to
      treatment had persistent (18)F-FDG uptake in bone and/or soft tissue on follow
      up. Patients with good clinical response had uptake confined to the margins of
      the destroyed disc. None of these patients had recurrent infection, even if
      antibiotics had already been discontinued at the time of the follow-up scan.
      CONCLUSIONS: (18)F-FDG uptake confined to the margins of a destroyed disc after
      antibiotic therapy of pyogenic spine infection must not be considered indicative
      of persistent infection and likely represents mechanically induced inflammation.
      (18)F-FDG uptake in bone or soft tissue does indicate active infection.
      Quantification of activity could not reliably differentiate patients with active
      infection from those without active infection and those who had had a successful
      response to therapy. The pattern of activity is critical to accurate
      interpretation.

PMID- 25592989
TI  - CO-029 is overexpressed in gastric cancer and mediates the effects of EGF on
      gastric cancer cell proliferation and invasion.
AB  - Tetraspanins are cell-surface glycoproteins and have received attention recently
      as both suppressors and promoters of metastasis. CO-029 is a member of the
      tetraspanin family and is implicated to be a metastasis-promoting tetraspanin in
      some cancers. However, the role of CO-029 in gastric cancer remains unexplored.
      The present study aimed to investigate the expression of CO-029 in gastric cancer
      tissues and to determine whether CO-029 is involved in the effects of epidermal
      growth factor (EGF) on gastric cancer cell proliferation and invasion. We
      collected clinical samples and found that the expression of CO-029 was increased
      both at the mRNA level and protein level in gastric cancer tissues in comparison
      to normal and tumor-adjacent tissues, as demonstrated by RT-qPCR and western blot
      analysis, respectively. Furthermore, we performed an in vitro experiment using
      AGS cells and observed that EGF promoted AGS cell proliferation and enhanced the
      invasion ability of the AGS cells, as shown by MTT assay and cell invasion assay,
      respectively. To the best of our knowledge, our results reveal for the first
      time, that CO-029 expression was affected by EGF in a concentration- time
      dependent manner. The knockdown of CO-029 attenuated the effects of EGF on
      gastric cancer cell proliferation and invasion. These findings suggest that CO
      029 is an oncogene in human gastric cancer and that CO-029 at least partially
      mediates the effects of EGF on gastric cancer cell proliferation and invasion.
      Our data may provide a novel target for therapeutic intervention in human gastric
      cancer.

PMID- 25592986
TI  - Role of siglecs and related glycan-binding proteins in immune responses and
      immunoregulation.
AB  - Virtually all cells and extracellular material are heavily decorated by various
      glycans, yet our understanding of the structure and function of these moieties
      lags behind the understanding of nucleic acids, lipids, and proteins. Recent
      years have seen a tremendous acceleration of knowledge in the field of
      glycobiology, revealing many intricacies and functional contributions that were
      previously poorly appreciated or even unrecognized. This review highlights
      several topics relevant to glycoimmunology in which mammalian and pathogen
      derived glycans displayed on glycoproteins and other scaffolds are recognized by
      specific glycan-binding proteins (GBPs), leading to a variety of proinflammatory
      and anti-inflammatory cellular responses. The focus for this review is mainly on
      2 families of GBPs, sialic acid-binding immunoglobulin-like lectins (siglecs) and
      selectins, that are involved in multiple steps of the immune response, including
      distinguishing pathogens from self, cell trafficking to sites of inflammation,
      fine-tuning of immune responses leading to activation or tolerance, and
      regulation of cell survival. Importantly for the clinician, accelerated rates of
      discovery in the field of glycoimmunology are being translated into innovative
      medical approaches that harness the interaction of glycans and GBPs to the
      benefit of the host and might soon lead to novel diagnostics and therapeutics. 

PMID- 25592990
TI  - Middle East respiratory syndrome in the shadow of Ebola.

PMID- 25592992
TI  - Data-driven discovery of energy materials: efficient BaM2Si3O10 : Eu2+ (M = Sc,
      Lu) phosphors for application in solid state white lighting.
AB  - In developing phosphors for application in solid state lighting, it is
      advantageous to target structures from databases with highly condensed polyhedral
      networks that produce rigid host compounds. Rigidity limits channels for non
      radiative decay that will decrease the luminescence quantum yield.
      BaM(2)Si(3)O(10) (M = Sc, Lu) follows this design criterion and is studied here
      as an efficient Eu(2+)-based phosphor. M = Sc(3+) and Lu(3+) compounds with
      Eu(2+) substitution were prepared and characterized using synchrotron X-ray
      powder diffraction and photoluminescence spectroscopy. Substitution with Eu(2+)
      according to Ba(1-x)Eu(x)Sc(2)Si(3)O(10) and Ba(1-x)Eu(x)Lu(2)Si(3)O(10) results
      in UV-to-blue and UV-to-blue-green phosphors, respectively. Interestingly,
      substitution with Eu(2+) in the Lu(3+) containing material produces two emission
      peaks at low temperature and with 365 nm excitation, as allowed by the two
      substitution sites. The photoluminescence of the Sc(3+) compound is robust at
      high temperature, decreasing by only 25% of its room temperature intensity at 503
      K, while the Lu-analogue suffers a large drop (75%) from its room temperature
      intensity. The decrease in emission intensity is explained as stemming from
      charge transfer quenching due to the short distances separating the luminescent
      centers on the Lu(3+) substitution site. The correlation between structure and
      optical response in these two compounds indicates that even though the structures
      are three-dimensionally connected, high symmetry is required to prevent
      structural distortions that could impact photoluminescence.

PMID- 25592993
TI  - Retraction. Early magnitude estimation for the MW7.9 Wenchuan earthquake using
      progressively expanded P-wave time window.

PMID- 25592991
TI  - Quantitative comparison of structure and dynamics of elastin following three
      isolation schemes by 13C solid state NMR and MALDI mass spectrometry.
AB  - Methods for isolating elastin from fat, collagen, and muscle, commonly used in
      the design of artificial elastin based biomaterials, rely on exposing tissue to
      harsh pH levels and temperatures that usually denature many proteins. At present,
      a quantitative measurement of the modifications to elastin following isolation
      from other extracellular matrix constituents has not been reported. Using magic
      angle spinning (13)C NMR spectroscopy and relaxation methodologies, we have
      measured the modification in structure and dynamics following three known
      purification protocols. Our experimental data reveal that the (13)C spectra of
      the hydrated samples appear remarkably similar across the various purification
      methods. Subtle differences in the half maximum widths were observed in the
      backbone carbonyl suggesting possible structural heterogeneity across the
      different methods of purification. Additionally, small differences in the
      relative signal intensities were observed between purified samples. Lyophilizing
      the samples results in a reduction of backbone motion and reveals additional
      differences across the purification methods studied. These differences were most
      notable in the alanine motifs indicating possible changes in cross-linking or
      structural rigidity. The measured correlation times of glycine and proline
      moieties are observed to also vary considerably across the different purification
      methods, which may be related to peptide bond cleavage. Lastly, the relative
      concentration of desmosine cross-links in the samples quantified by MALDI mass
      spectrometry is reported. 

PMID- 25592994
TI  - Visual-motor deficits relate to altered gray and white matter in young adults
      born preterm with very low birth weight.
AB  - Individuals born preterm and at very low birth weight (birth weight <= 1500 g)
      are at an increased risk of perinatal brain injury and neurodevelopmental
      deficits over the long term. This study examined whether this clinical group has
      more problems with visual-motor integration, motor coordination, and visual
      perception compared to term-born controls, and related these findings to cortical
      surface area and thickness and white matter fractional anisotropy. Forty-seven
      preterm-born very low birth weight individuals and 56 term-born controls were
      examined at 18-22 years of age with a combined cognitive, morphometric MRI, and
      diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills
      were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor
      Integration-V (VMI) copying test and its supplemental tests of motor coordination
      and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging
      were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise
      maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were
      used to explore the relationship between MRI findings and cognitive results. Very
      low birth weight individuals had significantly lower scores on the copying and
      motor coordination tests compared with controls. In the very low birth weight
      group, VMI scores showed significant positive relationships with cortical surface
      area in widespread regions, with reductions of the superior temporal gyrus,
      insula, and medial occipital lobe in conjunction with the posterior ventral
      temporal lobe. Visual perception scores also showed positive relationships with
      cortical thickness in the very low birth weight group, primarily in the lateral
      occipito-temporo-parietal junction, the superior temporal gyrus, insula, and
      superior parietal regions. In the very low birth weight group, visual-motor
      performance correlated positively with fractional anisotropy especially in the
      corpus callosum, inferior fronto-occipital fasciculus bilaterally, and anterior
      thalamic radiation bilaterally, driven primarily by an increase in radial
      diffusivity. VMI scores did not demonstrate a significant relationship to
      cortical surface area, cortical thickness, or diffusion measures in the control
      group. Our results indicate that visual-motor integration problems persist into
      adulthood for very low birth weight individuals, which may be due to structural
      alterations in several specific gray-white matter networks. Visual-motor deficits
      appear related to reduced surface area of motor and visual cortices and disturbed
      connectivity in long association tracts containing visual and motor information.
      We conjecture that these outcomes may be due to perinatal brain injury or
      aberrant cortical development secondary to injury or due to very preterm birth.

PMID- 25592995
TI  - Mathematical framework for large-scale brain network modeling in The Virtual
      Brain.
AB  - In this article, we describe the mathematical framework of the computational
      model at the core of the tool The Virtual Brain (TVB), designed to simulate
      collective whole brain dynamics by virtualizing brain structure and function,
      allowing simultaneous outputs of a number of experimental modalities such as
      electro- and magnetoencephalography (EEG, MEG) and functional Magnetic Resonance
      Imaging (fMRI). The implementation allows for a systematic exploration and
      manipulation of every underlying component of a large-scale brain network model
      (BNM), such as the neural mass model governing the local dynamics or the
      structural connectivity constraining the space time structure of the network
      couplings. Here, a consistent notation for the generalized BNM is given, so that
      in this form the equations represent a direct link between the mathematical
      description of BNMs and the components of the numerical implementation in TVB.
      Finally, we made a summary of the forward models implemented for mapping
      simulated neural activity (EEG, MEG, sterotactic electroencephalogram (sEEG),
      fMRI), identifying their advantages and limitations. 

PMID- 25592997
TI  - A new compression format for fiber tracking datasets.
AB  - A single diffusion MRI streamline fiber tracking dataset may contain hundreds of
      thousands, and often millions of streamlines and can take up to several gigabytes
      of memory. This amount of data is not only heavy to compute, but also difficult
      to visualize and hard to store on disk (especially when dealing with a collection
      of brains). These problems call for a fiber-specific compression format that
      simplifies its manipulation. As of today, no fiber compression format has yet
      been adopted and the need for it is now becoming an issue for future connectomics
      research. In this work, we propose a new compression format, .zfib, for
      streamline tractography datasets reconstructed from diffusion magnetic resonance
      imaging (dMRI). Tracts contain a large amount of redundant information and are
      relatively smooth. Hence, they are highly compressible. The proposed method is a
      processing pipeline containing a linearization, a quantization and an encoding
      step. Our pipeline is tested and validated under a wide range of DTI and HARDI
      tractography configurations (step size, streamline number, deterministic and
      probabilistic tracking) and compression options. Similar to JPEG, the user has
      one parameter to select: a worst-case maximum tolerance error in millimeter (mm).
      Overall, we find a compression factor of more than 96% for a maximum error of
      0.1mm without any perceptual change or change of diffusion statistics (mean
      fractional anisotropy and mean diffusivity) along bundles. This opens new
      opportunities for connectomics and tractometry applications. 

PMID- 25592996
TI  - Edge density imaging: mapping the anatomic embedding of the structural connectome
      within the white matter of the human brain.
AB  - The structural connectome has emerged as a powerful tool to characterize the
      network architecture of the human brain and shows great potential for generating
      important new biomarkers for neurologic and psychiatric disorders. The edges of
      the cerebral graph traverse white matter to interconnect cortical and subcortical
      nodes, although the anatomic embedding of these edges is generally overlooked in
      the literature. Mapping the paths of the connectome edges could elucidate the
      relative importance of individual white matter tracts to the overall network
      topology of the brain and also lead to a better understanding of the effect of
      regionally-specific white matter pathology on cognition and behavior. In this
      work, we introduce edge density imaging (EDI), which maps the number of network
      edges that pass through every white matter voxel. Test-retest analysis shows good
      to excellent reliability for edge density (ED) measurements, with consistent
      results using different cortical and subcortical parcellation schemes and
      different diffusion MR imaging acquisition parameters. We also demonstrate that
      ED yields complementary information to both traditional and emerging voxel-wise
      metrics of white matter microstructure and connectivity, including fractional
      anisotropy, track density, fiber orientation dispersion and neurite density. Our
      results demonstrate spatially ordered variations of ED throughout the white
      matter, notably including greater ED in posterior than anterior cerebral white
      matter. The EDI framework is employed to map the white matter regions that are
      enriched with pathways connecting rich club nodes and also those with high
      densities of intra-modular and inter-modular edges. We show that periventricular
      white matter has particularly high ED and high densities of rich club edges,
      which is significant for diseases in which these areas are selectively affected,
      ranging from white matter injury of prematurity in infants to leukoaraiosis in
      the elderly. Using edge betweenness centrality, we identify specific white matter
      regions involved in a large number of shortest paths, some containing highly
      connected rich club edges while others are relatively isolated within individual
      modules. Overall, these findings reveal an intricate relationship between white
      matter anatomy and the structural connectome, motivating further exploration of
      EDI for biomarkers of cognition and behavior. 

PMID- 25592998
TI  - Characterizing nonlinear relationships in functional imaging data using
      eigenspace maximal information canonical correlation analysis (emiCCA).
AB  - Many important problems in the analysis of neuroimages can be formulated as
      discovering the relationship between two sets of variables, a task for which
      linear techniques such as canonical correlation analysis (CCA) have been commonly
      used. However, to further explore potential nonlinear processes that might co
      exist with linear ones in brain function, a more flexible method is required.
      Here, we propose a new unsupervised and data-driven method, termed the eigenspace
      maximal information canonical correlation analysis (emiCCA), which is capable of
      automatically capturing the linear and/or nonlinear relationships between various
      data sets. A simulation confirmed the superior performance of emiCCA in
      comparison with linear CCA and kernel CCA (a nonlinear version of CCA). An emiCCA
      framework for functional magnetic resonance imaging (fMRI) data processing was
      designed and applied to data from a real motor execution fMRI experiment. This
      analysis uncovered one linear (in primary motor cortex) and a few nonlinear
      networks (e.g., in the supplementary motor area, bilateral insula, and
      cerebellum). This suggests that these various task-related brain areas are part
      of networks that also contribute to the execution of movements of the hand. These
      results suggest that emiCCA is a promising technique for exploring various data. 

PMID- 25592999
TI  - Robotic radical cystectomy: so far, so good--what next?

PMID- 25593002
TI  - Critical care of Ebola patients: a crisis situation.

PMID- 25593000
TI  - Fast and robust group-wise eQTL mapping using sparse graphical models.
AB  - BACKGROUND: Genome-wide expression quantitative trait loci (eQTL) studies have
      emerged as a powerful tool to understand the genetic basis of gene expression and
      complex traits. The traditional eQTL methods focus on testing the associations
      between individual single-nucleotide polymorphisms (SNPs) and gene expression
      traits. A major drawback of this approach is that it cannot model the joint
      effect of a set of SNPs on a set of genes, which may correspond to hidden
      biological pathways. RESULTS: We introduce a new approach to identify novel group
      wise associations between sets of SNPs and sets of genes. Such associations are
      captured by hidden variables connecting SNPs and genes. Our model is a linear
      Gaussian model and uses two types of hidden variables. One captures the set
      associations between SNPs and genes, and the other captures confounders. We
      develop an efficient optimization procedure which makes this approach suitable
      for large scale studies. Extensive experimental evaluations on both simulated and
      real datasets demonstrate that the proposed methods can effectively capture both
      individual and group-wise signals that cannot be identified by the state-of-the
      art eQTL mapping methods. CONCLUSIONS: Considering group-wise associations
      significantly improves the accuracy of eQTL mapping, and the successful multi
      layer regression model opens a new approach to understand how multiple SNPs
      interact with each other to jointly affect the expression level of a group of
      genes.

PMID- 25593003
TI  - Study identifies how common cold triggers asthma attacks.

PMID- 25593001
TI  - Efficacy of 3D conforming nickel titanium rotary instruments in eliminating canal
      wall bacteria from oval-shaped root canals.
AB  - OBJECTIVES: To evaluate the effectiveness of TRUShape(r) 3D Conforming Files,
      compared with Twisted Files, in reducing bacteria load from root canal walls, in
      the presence or absence of irrigant agitation. METHODS: Extracted human premolars
      with single oval-shaped canals were infected with Enterococcus faecalis. Teeth in
      Group I (N=10; NaOCl and QMix(r) 2in1 as respective initial and final irrigants)
      were subdivided into 4 subgroups: (A) TRUShape(r) instrumentation without
      irrigant activation; (B) TRUShape(r) instrumentation with sonic irrigant
      agitation; (C) Twisted Files without irrigant agitation; (D) Twisted Files with
      sonic irrigant agitation. To remove confounding factor (antimicrobial irrigants),
      teeth in Group II (N=10) were irrigated with sterile saline, using the same
      subgroup designations. Specimens before and after chemomechanical debridement
      were cultured for quantification of colony-forming units (CFUs). Data from each
      group were analyzed separately using two-factor ANOVA and Holm-Sidak multiple
      comparison (alpha=0.05). Canal wall bacteria were qualitatively examined using
      scanning electron microscopy (SEM) and light microscopy of Taylor-modified Brown
      and Brenn-stained demineralised sections. RESULTS: CFUs from subgroups in Group I
      were not significantly different (P=0.935). For Group II, both file type
      (P<0.001) and irrigant agitation (P<0.001) significantly affected log-reduction
      in CFU concentrations. The interaction of these two factors was not significant
      (P=0.601). Although SEM showed reduced canal wall bacteria, bacteria were present
      within dentinal tubules after rotary instrumentation, as revealed by light
      microscopy of longitudinal root sections. CONCLUSIONS: TRUShape(r) files removed
      significantly more canal wall bacteria than Twisted Files when used without an
      antibacterial irrigant; the latter is required to decontaminate dentinal tubules.
      CLINICAL SIGNIFICANCE: Root canal disinfection should not be focused only on a
      mechanistic approach. Rather, the rational choice of a rotary instrumentation
      system should be combined with the use of well-tested antimicrobial irrigants and
      delivery/agitation techniques to establish a clinically realistic chemomechanical
      debridement protocol.

PMID- 25593004
TI  - Bisphenol A linked to wheeze and reduced lung function.

PMID- 25593005
TI  - South Africa confronts colliding respiratory epidemics.

PMID- 25593006
TI  - Travelling with COPD.

PMID- 25593008
TI  - Reduced lower leg muscle activity while balancing on cobblestone shaped surfaces.
AB  - The purpose of this study was to test the hypothesis that muscle intensity and
      ankle joint motion will be greater when balancing on a surface shaped like a
      cobblestone pathway than on a smooth surface. Nineteen healthy male and female
      subjects participated in this study. Electromyographic (EMG) activity of the
      soleus, gastrocnemii medialis and lateralis, peroneus longus and tibialis
      anterior and ankle dorsiflexion/plantarflexion and eversion/inversion were
      recorded for unilateral balancing tasks on a hard smooth (control), soft smooth
      and two cobblestone shaped balance surfaces. Mean ankle kinematics did not differ
      between conditions. EMG intensity of the lower leg muscles were significant lower
      for the cobblestone shaped surface than for the control surface (-40 to -80%;
      P<.01). EMG intensity of the lower leg muscles were significantly higher for the
      soft smooth surface than for the control surface (+12 to +30%; P<.01). Different
      balance strategies or tendon stretching may be responsible for these differences.
      Not only material properties but also surface shape of balance surfaces should be
      considered to optimize training output and tailored to the specific goal of a
      training regimen.

PMID- 25593009
TI  - Medicaol, a strigolactone identified as a putative didehydro-orobanchol isomer,
      from Medicago truncatula.
AB  - A major strigolactone produced by the model legume Medicago truncatula (barrel
      medic) has been tentatively identified as a didehydro-orobanchol isomer. In this
      study, a putative didehydro-orobanchol isomer was isolated from root exudates
      collected from barrel medic grown hydroponically under phosphate-starved
      conditions. The structure and absolute configurations of this strigolactone,
      named medicaol, were determined by a combination of spectroscopic analysis and
      spectral comparison with 4-deoxymedicaol which was synthesized using solvolysis
      and rearrangement of hydroxymethylhexahydroindenone to tetrahydroazulenone as a
      key step. Medicaol has a seven-membered cycloheptadiene in the A ring instead of
      a typical six-membered cyclohexene. Medicaol and 4-deoxymedicaol showed activity
      comparable to their corresponding six-membered A ring relatives, orobanchol and 4
      deoxyorobanchol (ent-2'-epi-5-deoxystrigol), in inducing hyphal branching of
      germinating spores of an arbuscular mycorrhizal fungus Gigaspora margarita.
      Plausible biosynthetic pathways from 4-deoxyorobanchol to medicaol are also
      proposed. 

PMID- 25593010
TI  - Biosynthesis of 20-hydroxyecdysone in plants: 3beta-hydroxy-5beta-cholestan-6-one
      as an intermediate immediately after cholesterol in Ajuga hairy roots.
AB  - 3beta-Hydroxy-5beta-cholestan-6-one was identified in the EtOAc extract of Ajuga
      hairy roots by micro-analysis using LC-MS/MS in the multiple reaction mode (MRM).
      Furthermore, administration of (2,2,4,4,7,7-(2)H6)- and (2,2,4,4,6,7,7-(2)H7)
      cholesterols to the hairy roots followed by LC-MS/MS analysis of the EtOAc
      extract of the hairy roots indicated that cholesterol was converted to the 5beta
      ketone with hydrogen migration from the C-6 to the C-5 position. These findings,
      in conjunction with the previous observation that the ketone was efficiently
      converted to 20-hydroxyecdysone, strongly suggest that the 5beta-ketone is an
      intermediate immediately formed after cholesterol during 20-hydroxyecdysone
      biosynthesis in Ajuga sp. In addition, the mechanism of the 5beta-ketone
      formation from cholesterol is discussed. 

PMID- 25593011
TI  - Cloning and functional characterization of a 4-coumarate CoA ligase from
      liverwort Plagiochasma appendiculatum.
AB  - Plant phenylpropanoids represent a large group of secondary metabolites which
      have played an important role in terrestrial plant life, beginning with the
      evolution of land plants from primitive green algae. 4-Coumarate: coenzyme A
      ligase (4CL) is a provider of activated thioester substrates within the
      phenylpropanoid synthesis pathway. Although 4CLs have been extensively
      characterized in angiosperm, gymnosperm and moss species, little is known of
      their functions in liverworts. Here, a 4CL homolog (designated as Pa4CL1) was
      isolated from the liverwort species Plagiochasma appendiculatum. The full-length
      cDNA sequence of Pa4CL1 contains 1644bp and is predicted to encode a protein with
      547amino acids. The gene products were 40-50% identical with 4CL sequences
      reported in public databases. The recombinant protein was heterologously
      expressed in Escherichia coli and exhibited a high level of 4CL activity,
      catalyzing formation of hydroxycinnamate-CoA thioesters by a two-step reaction
      mechanism from corresponding hydroxycinnamic acids. Kinetic analysis indicated
      that the most favorable substrate for Pa4CL1 is p-coumaric acid. The
      transcription of Pa4CL1 was induced when P. appendiculatum thallus was treated
      with either salicylic acid or methyl jasmonate. 

PMID- 25593012
TI  - Mutation of the gene encoding monothiol glutaredoxin (GrxD) in Pseudomonas
      aeruginosa increases its susceptibility to polymyxins.
AB  - Pseudomonas aeruginosa is a frequent cause of hospital-acquired infections that
      have a high mortality rate because of its innate drug resistance. Polymyxins are
      recognised as the last-line antibiotics for the treatment of multidrug-resistant
      (MDR) P. aeruginosa. In this study, the link between monothiol glutaredoxin
      (GrxD), which catalyses the reduction of disulphide bonds of various substrates
      in P. aeruginosa, and antibiotic resistance was examined. A P. aeruginosa
      DeltagrxD mutant strain was constructed. The DeltagrxD mutant showed
      significantly increased susceptibility to polymyxin B (PMB) compared with the
      wild-type P. aeruginosa PAO1. Site-directed mutagenesis was performed to generate
      amino acid substitutions in GrxD, and the ability of mutated grxD genes to confer
      resistance to PMB in the DeltagrxD mutant was tested. The results indicated that
      residue C29 at the active site of GrxD is important for protection against
      polymyxin killing in the mutant. Polymyxin killing of PAO1 and the DeltagrxD
      mutant did not appear to involve hydroxyl radicals generated by antibiotic
      treatment because increased susceptibility of the mutant to PMB was also observed
      under anaerobic growth as well as aerobically in the presence of the iron
      chelator 2,2'-dipyridyl. Thus, GrxD could be a target for the development of
      agents that enhance the effectiveness of PMB in treating clinically important MDR
      P. aeruginosa infections. 

PMID- 25593013
TI  - Quinolone resistance-determining region mutations and the plasmid-mediated
      quinolone resistance gene qnrS played important roles in decreased susceptibility
      to fluoroquinolones among Shigella isolates in southeast China between 1998 and
      2013.

PMID- 25593014
TI  - Livestock-associated meticillin-resistant Staphylococcus aureus in Asia: an
      emerging issue?
AB  - In addition to being a human pathogen, Staphylococcus aureus causes an array of
      infections in economically important livestock animals, particularly pigs. In
      Asia, there have been few reports on livestock-associated meticillin-resistant S.
      aureus (LA-MRSA), mostly from developed countries, with very few data available
      from resource-limited countries, not because of low prevalence but probably due
      to a shortage of diagnostic facilities. Unlike the wide spread of sequence type
      398 (ST398) LA-MRSA in European countries and North America, ST9 predominates in
      most Asian countries. The prevalence of LA-MRSA among pigs in Asian countries
      varied widely (0.9-42.5%). The prevalence may vary by geographic location, age of
      pigs and sampling methodologies. Among pig farmers, the prevalence of nasal MRSA
      colonisation varied from 5.5% in Malaysia to 15% in China and 19.2% in Taiwan.
      Although most LA-MRSA isolates in Asia are of the same ST, molecular
      characteristics are not all the same. Dominant isolates in China were
      characterised as spa type t899-SCCmec III and t899-SCCmec IVb or V for isolates
      in Hong Kong, and t899-untypeable SCCmec for Taiwan. Dominant isolates in
      Malaysia were spa type t4358-SCCmec V and t337-SCCmec IX for isolates in
      Thailand. In addition, MRSA ST221 was reported in Japan and MRSA ST398 was
      isolated from commercial pigs in South Korea. Attention should be paid because
      pigs could become an important reservoir for MRSA and spread them to humans, as
      observed in many countries. There is a potential risk from the livestock
      reservoir to community and hospitals. 

PMID- 25593015
TI  - A randomized phase II efficacy and correlative studies of cetuximab with or
      without sorafenib in recurrent and/or metastatic head and neck squamous cell
      carcinoma.
AB  - INTRODUCTION: A combination of cetuximab and sorafenib in patients with recurrent
      and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were
      assessed for potential benefit. MATERIAL AND METHODS: In a randomized phase II
      study, R/M HNSCC patients were treated with cetuximab 400mg/m(2) IV on day 1
      followed by 250mg/m(2) IV weekly (Arm A), or cetuximab at the same dose/schedule
      plus sorafenib 400mg PO twice-a-day (Arm B). Each cycle was 21days. Tumor p16 and
      HPV status, and plasma immunomodulatory cytokine levels were assessed. RESULTS:
      Of 55 patients enrolled (Arm A-27, Arm B-28), 52 patients received assigned
      treatments and 43 were evaluable for response. Overall response rate was 8% for
      both arms. Median overall survival (OS) and progression-free survival (PFS) were
      9.0 and 3.0months in Arm A, and 5.7 and 3.2months in Arm B, respectively. Forty
      four patients had tumors available for p16 staining (35-negative, 9-positive).
      Three of nine p16-positive tumors were also HPV positive. The p16-negative
      patients had significantly better PFS compared to the p16-positive patients (3.7
      vs. 1.6months; p-value: 0.03), regardless of study arms. Twenty-four plasma
      samples were tested for 12 cytokine levels and patients with higher TGFbeta1
      levels had inferior PFS compared to lower levels (1.9 vs. 4.7months; adjusted p
      value: 0.015), regardless of study arms. CONCLUSIONS: A subset of R/M patients
      with p16-negative tumors or lower plasma TGFbeta1 levels had longer PFS given the
      cetuximab-based therapy. However, both arms showed only modest response and
      sorafenib given with cetuximab did not demonstrate clinical benefit.

PMID- 25593017
TI  - Barriers to clinical trial recruitment in head and neck cancer.
AB  - Despite substantial improvements in the treatment of head and neck cancer (HNC)
      over the last two decades, overall survival rates remain unsatisfactory. The need
      for improved therapeutic approaches for HNC patients is hampered by low patient
      recruitment rates in HNC clinical trials, particularly Phase III studies. Based
      on an analysis of ClinicalTrials.gov, this article identified several potential
      barriers to patient recruitment in Phase I-III clinical trials of treatments for
      HNC. Of 694 HNC trials identified on ClinicalTrials.gov from multiple sites
      worldwide, 91 (13.1%) were identified as either terminated, suspended or
      withdrawn; 27.5% (n=25) of these did not provide an additional reason for
      stopping recruitment early. Insufficient accrual was the most common reason
      provided for trial closure (n=23, 25.3%). Possible reasons for the insufficient
      accrual rates include the inappropriate designs of these studies given the change
      in HNC tumour biology in the last 20years, the low incidence of the disease, and
      the diversity of treatment standards and referral processes across countries.
      Given the low numbers of drugs approved for HNC, it is important that barriers to
      recruitment in this field are addressed to allow new therapies to be successfully
      validated in completed clinical trials. This review discusses how these accrual
      challenges may be overcome with changes to clinical trial designs, including
      their adaptation to specific subgroups, such as human papillomavirus-positive
      patients. 

PMID- 25593018
TI  - Antiviral effects of Jinxin oral liquid against respiratory syncytial virus
      infection in the BALB/c mice model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jinxin oral liquid (JOL) is used in traditional
      Chinese medicine (TCM) to treat influenza, cough, asthma, and viral pneumonia, on
      the basis of Ma Xing Shi Gan Tang (MXSGT) and the clinical experience of
      Professor Wang Shouchuan, one of the most prestigious pediatricians in China. AIM
      OF STUDY: To investigate the anti-inflammatory and antiviral activities of JOL in
      mice infected with respiratory syncytial virus (RSV). MATERIALS AND METHODS: Mice
      were orally administered JOL at doses of 27.6 g kg(-1) d(-1) and 55.2 g kg(-1) d(
      1) for 1, 3, or 6d after RSV challenge. The viral loads in the lung tissue were
      measured by real-time RT-PCR. The levels of IFN-beta in bronchoalveolar lavage
      fluid (BLAF) and lung tissue were detected by ELISA and real-time RT-PCR,
      respectively. The mRNA and protein expression of TLR3, IRF3, and SOCS1 were
      detected by real-time RT-PCR and western blot, respectively. The protein
      expression of phoshorylated-IRF3 (p-IRF3) was detected by western blot. RESULTS:
      JOL significantly ameliorated lung inflammation in RSV-infected mice, and
      significantly reduced the viral load in the lung tissues. On days 2 and 4 after
      infection, the mRNA and protein expression of IFN-beta, TLR3, IRF3 (p-IRF3), and
      SOCS1 were significantly downregulated in RSV-infected mice treated with JOL.
      However, 7d after infection, JOL significantly upregulated the RSV-induced
      decrease in IFN-beta, TLR3, and IRF3 (p-IRF3), but reduced SOCS1 expression.
      CONCLUSIONS: JOL ameliorated lung inflammation and inhibited virus replication
      significantly in RSV-infected mice. During early stage infection, the effect of
      JOL was improved through inhibition of the TLR3-IRF3-IFN-beta signaling pathway
      and the expression of SOCS1, whereas during the later stage of infection, JOL
      upregulated the expression of key signaling molecules in the TLR3 signaling
      pathway and downregulated the expression of SOCS1.

PMID- 25593016
TI  - A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible
      oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or
      metastatic head and neck squamous cell cancer.
AB  - INTRODUCTION: The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase
      (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is frequently
      altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral,
      irreversible, pan-isoform inhibitor of PI3K. Preclinical models revealed synergy
      with docetaxel and a phase 1 trial demonstrated tolerability of this combination.
      This randomized phase 2 study evaluated PX-866 combined with docetaxel in
      patients with advanced, refractory HNSCC. METHODS: Patients with locally
      advanced, recurrent or metastatic HNSCC who had received at least one and no more
      than two prior systemic treatment regimens were randomized (1:1) to a combination
      of docetaxel (75mg/m(2) IV every 21days) with or without PX-866 (8mg PO daily;
      Arms A and B, respectively). The primary endpoint was progression free survival
      (PFS). Secondary endpoints included objective response rate (RR), overall
      survival (OS), toxicity, and correlation of biomarker analyses with efficacy
      outcomes. RESULTS: 85 patients were enrolled. There was a non-significant
      improvement in response rate in the combination arm (14% vs. 5%; P=0.13). Median
      PFS was 92days in Arm A and 82days in Arm B (P=0.42). There was no difference in
      OS between the two arms (263 vs. 195days; P=0.62). Grade 3 or higher adverse
      events were infrequent, but more common in the combination arm with respect to
      diarrhea (17% vs. 2%), nausea (7% vs. 0%), and febrile neutropenia (21% vs. 5%);
      grade 3 or higher anemia was more frequent in arm B (7% vs. 27%). PIK3CA
      mutations or PTEN loss were infrequently observed. CONCLUSION: The addition of PX
      866 to docetaxel did not improve PFS, RR, or OS in patients with advanced,
      refractory HNSCC without molecular pre-selection.

PMID- 25593020
TI  - In situ activation of benzyl alcohols with XtalFluor-E: formation of 1,1
      diarylmethanes and 1,1,1-triarylmethanes through Friedel-Crafts benzylation.
AB  - The Friedel-Crafts benzylation of arenes using benzyl alcohols activated in situ
      with XtalFluor-E is described. A wide range of 1,1-diarylmethanes and 1,1,1
      triarylmethanes were prepared under experimentally simple and mild conditions,
      without the need for a transition metal or a strong Lewis acid. Notably, the
      reactivity observed demonstrates the potential of XtalFluor-E to induce C-OH bond
      ionization and SN1 reactivity of benzylic alcohols. 

PMID- 25593019
TI  - Hyponatremia in the neurocritical care patient: An approach based on current
      evidence.
AB  - In the neurocritical care setting, hyponatremia is the commonest electrolyte
      disorder, which is associated with significant morbimortality. Cerebral salt
      wasting and syndrome of inappropriate antidiuretic hormone have been classically
      described as the 2 most frequent entities responsible of hyponatremia in
      neurocritical care patients. Nevertheless, to distinguish between both syndromes
      is usually difficult and useless as volume status is difficult to be determined,
      underlying pathophysiological mechanisms are still not fully understood, fluid
      restriction is usually contraindicated in these patients, and the first option in
      the therapeutic strategy is always the same: 3% hypertonic saline solution.
      Therefore, we definitively agree with the current concept of "cerebral salt
      wasting", which means that whatever is the etiology of hyponatremia, initially in
      neurocritical care patients the treatment will be the same: hypertonic saline
      solution. 

PMID- 25593021
TI  - Saccadic adaptation in visually normal individuals using saccadic endpoint
      variability from amblyopia.
AB  - PURPOSE: Saccadic adaptation is affected by the spatial variability of the
      adapting error signal. Recently, we have shown that saccadic adaptation is
      reduced in anisometropic amblyopia, possibly impacted by spatially imprecise
      saccades. Here, we tested this idea by quantifying the saccadic endpoint
      variability difference between people with anisometropic amblyopia and visually
      normal individuals. We then applied this difference to the second target step
      distribution during saccadic adaptation in visually normal people to test whether
      their performance diminished to a similar extent as participants with amblyopia.
      METHODS: Ten visually normal adults performed a double-step adaptation task (+/
      19 degrees , followed by 4 degrees  back-steps) with the nondominant eye under
      two conditions: "consistent error," using a constant back-step; and "variable
      error," using a variable (sigmadiff) back-step determined by subtracting the
      saccadic endpoint variability in controls from that in anisometropic amblyopia
      during amblyopic/nondominant eye viewing. Percentage change in saccadic gains,
      percentage retention, and adaptation time constants were analyzed. RESULTS:
      Percentage change in saccadic gains decreased significantly during the variable
      error condition (50% +/- 10%) compared to the consistent error condition (69% +/-
      9%; P = 0.0008). Percentage retention and time constants did not differ between
      conditions. The adaptation magnitude during the variable error condition was
      comparable to the previous percentage adaptation in people with anisometropic
      amblyopia during the consistent error condition with amblyopic eye viewing.
      CONCLUSIONS: Our findings indicate that adding exogenous spatial noise to the
      adapting step consistent with the saccadic endpoint variability difference
      between amblyopic and visually normal groups is sufficient to reduce saccadic
      adaptation in healthy individuals.

PMID- 25593022
TI  - Oxytocin expression and function in the posterior retina: a novel signaling
      pathway.
AB  - PURPOSE: Oxytocin (OXT) is recognized as an ubiquitously acting nonapeptide
      hormone that is involved in processes ranging from parturition to neural
      development. Its effects are mediated by cell signaling that occurs as a result
      of oxytocin receptor (OXTR) activation. We sought to determine whether the OXT
      OXTR signaling pathway is also expressed within the retina. METHODS:
      Immunohistochemistry using cell-specific markers was used to localize OXT within
      the rhesus retina. Reverse transcriptase PCR and immunohistochemistry were used
      to assess the expression of OXTR in both human and rhesus retina. Single-cell RT
      PCR and Western blot analyses were used to determine the expression of OXTR in
      cultured human fetal RPE (hfRPE) cells. Human fetal RPE cells loaded with FURA-2
      AM were studied by ratiometric Ca(2+) imaging to assess transient mobilization of
      intracellular Ca(2+) ([Ca(2+)]i). RESULTS: Oxytocin was expressed in the cone
      photoreceptor extracellular matrix of the rhesus retina. Oxytocin mRNA and
      protein were expressed in the human and rhesus RPE. Oxytocin mRNA and protein
      expression were observed in cultured hfRPE cells, and exposure of these cells to
      100 nM OXT induced a transient 79 +/- 1.5 nM increase of [Ca(2+)]i. CONCLUSIONS:
      Oxytocin and OXTR are present in the posterior retina, and OXT induces an
      increase in hfRPE [Ca(2+)]i. These results suggest that the OXT-OXTR signaling
      pathway is active in the retina. We propose that OXT activation of the OXTR
      occurs in the posterior retina and that this may serve as a paracrine signaling
      pathway that contributes to communication between the cone photoreceptor and the
      RPE.

PMID- 25593023
TI  - Local production of the alternative pathway component factor B is sufficient to
      promote laser-induced choroidal neovascularization.
AB  - PURPOSE: Complement factor B (CFB) is a required component of the alternative
      pathway (AP) of complement, and CFB polymorphisms are associated with age-related
      macular degeneration (AMD) risk. Complement factor B is made in the liver, but
      expression has also been detected in retina and retinal pigment epithelium (RPE)
      choroid. We investigated whether production of CFB by the RPE can promote AP
      activation in mouse choroidal neovascularization (CNV). METHODS: Transgenic mice
      expressing CFB under the RPE65 promoter were generated and crossed onto factor B
      deficient (CFB-KO) mice. Biological activity was determined in vitro using RPE
      monolayers and in vivo using laser-induced CNV. Contribution of systemic CFB was
      investigated using CFB-KO reconstituted with CFB-sufficient serum. RESULTS:
      Transgenic mice (CFB-tg) expressed CFB in RPE-choroid; no CFB was detected in
      serum. Cultured CFB-tg RPE monolayers secreted CFB apically and basally upon
      exposure to oxidative stress that was biologically active. Choroidal
      neovascularization sizes were comparable between wild-type and CFB-tg mice, but
      significantly increased when compared to lesions in CFB-KO mice. Injections of
      CFB-sufficient serum into CFB-KO mice resulted in partial reconstitution of
      systemic AP activity and significantly increased CNV size. CONCLUSIONS: Mouse RPE
      cells express and secrete CFB sufficient to promote RPE damage and CNV. This
      further supports that local complement production may regulate disease processes;
      however, the reconstitution experiments suggest that additional components may be
      sequestered from the bloodstream. Understanding the process of ocular complement
      production and regulation will further our understanding of the AMD disease
      process and the requirements of a complement-based therapeutic.

PMID- 25593025
TI  - Lamina cribrosa visibility using optical coherence tomography: comparison of
      devices and effects of image enhancement techniques.
AB  - PURPOSE: To compare the visibility of the lamina cribrosa (LC) in optic disc
      images acquired from 60 glaucoma and 60 control subjects using three optical
      coherence tomography (OCT) devices, with and without enhanced depth imaging (EDI)
      and adaptive compensation (AC). METHODS: A horizontal B-scan was acquired through
      the center of the disc using two spectral-domain (Spectralis and Cirrus; with and
      without EDI) and a swept-source (DRI) OCT. Adaptive compensation was applied post
      acquisition to improve image quality. To assess LC visibility, four masked
      observers graded the 1200 images in a randomized sequence. The anterior LC was
      graded from 0 to 4, the LC insertions from 0 to 2, and the posterior LC either 0
      or 1. The effect of EDI, AC, glaucoma severity, and other clinical/demographic
      factors on LC visibility was assessed using generalized estimating equations.
      RESULTS: The anterior LC was the most detectable feature, followed by the LC
      insertions. Adaptive compensation improved anterior LC visibility independent of
      EDI. Cirrus+EDI+AC generated the greatest anterior LC visibility grades (2.79/4).
      For LC insertions visibility, DRI+AC was the best method (1.10/2). Visibility of
      the posterior LC was consistently poor. Neither glaucoma severity nor
      clinical/demographic factors consistently affected LC visibility. CONCLUSIONS:
      Adaptive compensation is superior to EDI in improving LC visibility. Visibility
      of the posterior LC remains poor suggesting impracticality in using LC thickness
      as a glaucoma biomarker.

PMID- 25593024
TI  - Loss of citron kinase affects a subset of progenitor cells that alters late but
      not early neurogenesis in the developing rat retina.
AB  - PURPOSE: To understand how loss of citron kinase (CitK) affects retinal
      progenitor cells (RPCs) in the developing rat retina. METHODS: We compared
      knockout (KO) and wild-type (WT) retinae by immunohistochemistry. The TdT
      mediated dUTP terminal nick-end labeling (TUNEL) assay was performed to determine
      cell death. Pulse-chase experiments using 5-ethynyl-2'-deoxyuridine (EdU) were
      carried out to interrogate RPC behavior and in turn neurogenesis. RESULTS:
      Reverse transcription-polymerase chain reaction analysis showed that CitK was
      expressed at embryonic day (E)12 and was turned off at approximately postnatal
      day (P)4. Immunohistochemistry showed CitK being localized as puncta at the
      apical end of the outer neuroblastic layer (ONBL). Analyses during embryonic
      development showed that the KO retina was of comparable size to that of WT until
      E13. However, by E14, there was a reduction in the number of S-phase RPCs with a
      concomitant increase in TUNEL+ cells in the KO retina. Moreover, early
      neurogenesis, as reflected by retinal ganglion cell production, was not affected.
      Postnatal analysis of the retina showed that ONBL in the KO retina was reduced to
      half the size of that in WT and showed further degeneration. Immunohistochemistry
      revealed absence of Islet1+ bipolar cells at P2, which was further confirmed by
      EdU pulse-chase experiments. The CitK KO retinae underwent complete degeneration
      by P14. CONCLUSIONS: Our study showed that CitK is not required for a subset of
      RPCs before E14, but is necessary for RPC survival post E14. This in turn results
      in normal early embryonic neurogenesis, but severely compromised later embryonic
      and postnatal neurogenesis.

PMID- 25593026
TI  - The role of B cells in the early onset of the first demyelinating event of acute
      optic neuritis.
AB  - PURPOSE: We evaluated the molecular pathways that operate in the early phase of
      acute optic neuritis (ON) by studying gene expression profiles of peripheral
      blood mononuclear cells (PBMCs) subpopulations, including CD19(+) B cells,
      CD14(+) macrophages, and CD4(+) and CD8(+) T cells. METHODS: Samples of PBMC
      subpopulations were obtained from 18 MS patients within 96 hours of the acute
      onset of the first demyelinating event of ON, and from 14 age- and sex-matched
      healthy subjects. High throughput gene expression analysis was performed on
      samples from six ON patients and nine healthy subjects using Affymetrix
      technology. Data were analyzed using Partek software, and most informative genes
      (MIGs) were defined as genes with P < 0.01 and fold change > 2.0. Molecular
      pathways were analyzed by Ingenuity software. Verification of key MIGs was done
      on samples from five independent ON patients and five healthy subjects by
      quantitative (Q) RT-PCR and Western blot. Functional assay to test antigen
      presentation ability of sorted B cells was performed on blood samples from seven
      additional ON patients. RESULTS: Significantly differentiating gene expression
      signatures consisting of 467, 55, and 55 MIGs respective of CD19(+), CD14(+), and
      CD4(+) cells, were identified between ON and healthy subjects. No MIGs were
      detected for CD8(+) cells. The major involvement of CD19(+) B cells in the early
      stage of ON was characterized by enrichment of genes involved in activation of
      immune mechanisms (P = 3.2 * 10(-25) to 2.5 * 10(-3)), including cellular immune
      response (P = 7.1 * 10(-12)), B-cell cellular growth and proliferation (P = 1.0 *
      10(-7)), activation of immune cells trafficking pathways (P = 5.4 * 10(-15) to
      2.0 * 10(-3)), and stimulation of antigen presentation (P = 8.9 * 10(-11)). This
      massive B-cell-restricted initiation of the immune response in the early disease
      process of ON was followed by low CD14(+) and CD4(+) cells activity and CD8(+)
      cells anergy. CONCLUSIONS: Our findings demonstrate that CD19(+) B cells have a
      significant role in the pathogenesis of the first demyelinating event of acute ON
      and suggest their role as a possible target for immunomodulation.

PMID- 25593027
TI  - Quality of life of caregivers of children with congenital glaucoma: development
      and validation of a novel questionnaire (CarCGQoL).
AB  - PURPOSE: We developed and validated an instrument to measure the quality of life
      (QoL) of caregivers of children with primary congenital glaucoma (PCG): the
      Caregiver's Congenital Glaucoma Quality of Life (CarCGQoL) questionnaire.
      METHODS: A total of 70 caregivers of children with PCG under follow-up at a
      tertiary eye care center in India participated in a series of focus groups, and
      pre- and pilot testing phases in the development of the 45-item CarCGQoL
      questionnaire. Subsequently, this instrument was administered to 111 caregivers
      of children with PCG awaiting glaucoma surgery. Response to each item was rated
      on a four-category scale. Rasch analysis was used to validate the instrument's
      psychometric properties, such as unidimensionality (by principal components
      analysis [PCA] of residuals), item fit to model, measurement precision (by person
      separation [PS]), response category performance, differential item functioning
      (DIF), and targeting of items to participant's QoL. RESULTS: Categories required
      reorganization resulting in a shortened rating scale of 3 categories. The
      instrument showed misfit to the Rasch model and lacked unidimensionality.
      Deleting 15 items (obtained through PCA of residuals) restored unidimensionality,
      but additional items misfit, necessitating item reduction. In addition, 2 items
      showed DIF and were deleted. Finally, a 20-item CarCGQoL instrument showed good
      fit and unidimensionality. Targeting was good (0.69 logits) and PS was 2.51,
      indicating good measurement precision. CONCLUSIONS: We have developed a
      psychometrically robust 20-item caregiver derived questionnaire, the CarCGQoL,
      that is a valid and reliable measure of QoL of caregivers of children with PCG.
      Given its brevity, it is quick and easy to administer in the clinic, and has
      potential for use as an outcome measure in clinical trials of treatment of PCG.

PMID- 25593029
TI  - Involvement of intracellular calcium mobilization in IL-8 activation in human
      retinal pigment epithelial cells.
AB  - PURPOSE: Calcium signaling is an important intracellular pathway. Increased
      intracellular calcium is associated with cytokine regulation and inflammatory
      signals secretion. The purpose of this study is to understand the molecular
      mechanisms by which calcium signaling controls IL-8 activation in human RPE
      cells. METHODS: Fluorescence-based calcium imaging and different mutants of IL-8
      plasmids were used in this study. The IL-8 promoter activation, gene expression,
      and secretion were detected by using luciferase reporter assay, quantitative real
      time PCR (Q-PCR), and ELISA, respectively. In addition, pharmacological
      inhibitors and small interfering RNA (siRNA) were applied to clarify the
      mechanisms of IL-8 activation. RESULTS: Our study reported that intracellular
      calcium mobilization activated IL-8 gene expression and secretion. Application of
      pharmacological inhibitor BAY 11-7082, siRNA, and plasmids of the nuclear factor
      kappa light chain enhancer of activated B cells (NF-kappaB) binding site, we
      identified that NF-kappaB is the main transcription factor involved in
      intracellular calcium mobilization-mediated IL-8 activation in human RPE cells.
      CONCLUSIONS: Collectively, our findings highlight the important role of
      intracellular calcium mobilization in the activation of IL-8. These findings may
      be helpful for the clinical applications in the age-related macular degeneration
      (AMD) prevention and treatment.

PMID- 25593030
TI  - Automated retinal topographic maps measured with magnetic resonance imaging.
AB  - PURPOSE: Recent studies on ocular shape have raised increased interest in the
      peripheral characteristics of the eye, as it potentially triggers changes in the
      central vision. Current techniques are, however, not capable of accurately
      measuring the three-dimensional shape of the retina. We describe a new magnetic
      resonance imaging (MRI)-based method to obtain the retinal shape with high
      precision and use it to assess if differences in retinal shape could explain
      previously described trends in peripheral refraction. METHODS: Twenty-one healthy
      subjects were examined using high-field ocular MRI. The resulting data were
      automatically segmented and processed to calculate the retinal topographic map.
      We validated the method against partial coherence interferometry and assessed the
      reproducibility for four subjects. RESULTS: The retinal topographic maps describe
      the retinal shape with subpixel reproducibility (SD between sessions = 0.11 mm).
      Comparison with partial coherence interferometry showed a mean difference of 0.08
      mm, 95% confidence interval -0.39 to 0.55 mm, with a standard deviation of 0.23
      mm. The data give a possible geometric explanation for the previously described
      trend in myopic eyes toward relatively hyperopic refraction in the periphery,
      with full three-dimensional information. The retinal maps furthermore show small,
      submillimeter, irregularities that could have an important influence on the
      subjects' peripheral vision. CONCLUSIONS: The possibility to quantitatively
      characterize the full three-dimensional retinal shape by MRI offers new
      ophthalmologic possibilities, such as quantitative geometric description of
      staphyloma. It could in addition be used as a validation technique, independent
      of standard optical methods, to measure the peripheral retinal shape.

PMID- 25593028
TI  - Skewed expression of the genes encoding epigenetic modifiers in high-risk uveal
      melanoma.
AB  - PURPOSE: Monosomy 3 (M3) or the presence of a specific RNA expression profile,
      known as class 2, is strongly associated with death from uveal melanoma (UM).
      Given the important role of epigenetic processes in cancer development and
      progression, we compared the transcriptional profiles of a selection of
      epigenetic regulators between primary UM with a good and a bad prognosis.
      METHODS: Transcriptional levels of 59 epigenetic regulator genes were measured by
      quantitative PCR (qPCR) in 20 UM, 12 with monosomy of chromosome 3 (M3) and 8
      with disomy of chromosome 3 (D3). Validation was performed in an independent
      cohort. Expression levels were compared to clinicopathological characteristics,
      including class type. Bisulfite sequencing was used to evaluate the role of DNA
      methylation in gene silencing. RESULTS: In the first set of tumors, general
      downregulation of transcription of the genes encoding epigenetic regulatory
      enzymes was seen in association with M3. The 10 genes with the highest
      differential expression between M3 and D3 were selected and were analyzed in a
      second set of tumors. In the validation set, significantly lower levels of KAT2B
      (P = 0.008), HDAC11 (P = 0.009), KMT1C (P = 0.05), KDM4B (P = 0.003), KDM6B (P =
      0.04), and BMI-1 (P = 0.001) transcripts were found in tumors with M3/class 2.
      Methylation of C-phosphate-G (CpG) residues was not observed on the putative
      regulatory regions of KAT2B, KDM4B, or KDM6B. CONCLUSIONS: Expression levels of a
      number of histone-modifying genes and polycomb family members are significantly
      lower in uveal melanoma with monosomy 3/class 2, supporting a general
      dysregulation of epigenetic modifiers in UM with a bad prognosis.

PMID- 25593032
TI  - Colorectal cancer heterogeneity and targeted therapy: a case for molecular
      disease subtypes.
AB  - Personalized cancer medicine is becoming increasingly important in colorectal
      cancer treatment. Especially for targeted therapies, large variations between
      individual treatment responses exist. Predicting therapy response is of utmost
      significance, as it prevents overtreatment and adverse effects in patients. For
      EGFR-targeted therapy, many mechanisms of resistance have been uncovered, for
      example, mutations in KRAS and BRAF, and upregulation of alternative receptors.
      Currently, routine testing for all known modifiers of response is unpractical,
      and as a result, decision-making for anti-EGFR therapy is still largely based on
      assessing the mutation status of an individual gene (KRAS). Recently,
      comprehensive classifications of colorectal cancer have been presented that
      integrate many of the (epi-)genetic and microenvironmental factors that
      contribute to colorectal cancer heterogeneity. These classification systems are
      not only of prognostic value but also predict therapy efficacy, including the
      response to anti-EGFR agents. Therefore, molecular subtype-based stratification
      to guide therapeutic decisions is a promising new strategy that might overcome
      the shortcomings of single gene testing in colorectal cancer as well as in other
      malignancies. Furthermore, the development of new agents in a disease subtype
      specific fashion has the potential to transform drug-discovery studies and
      generate novel, more effective therapies.

PMID- 25593036
TI  - Morphological, molecular and virulence characterization of three Lencanicillium
      species infecting Asian citrus psyllids in Huangyan citrus groves.
AB  - Citrus greening or Huanglongbing (HLB) is caused by the infection of Candidatus
      Liberibacter spp. in citrus plants. Since Asian citrus psyllid is the primary
      vector of this bacterial pathogen, the spread of HLB can be mitigated by
      suppressing Asian citrus psyllid populations in citrus groves using
      entomopathogens. To expand the current data on entomopathogens infecting Asian
      citrus psyllids, we isolated and characterized three different entomopathogens.
      Strains ZJLSP07, ZJLA08, and ZJLP09 infected the Asian citrus psyllid, Diaphorina
      citri Kuwayama, in Huangyan citrus groves. Based on molecular and morphological
      analyses, two were identified as Lecanicillium attenuatum and Lecanicillium
      psalliotae, and the third was recognized as an unidentified species of the genus,
      Lecanicillium. The corrected mortalities caused by strains ZJLSP07, ZJLA08 were
      100% at 7days post-inoculation, while by ZJLP09 complete mortality occurred at
      6days after inoculation, with 1.0*10(8)conidia/ml at 25 degrees C and a relative
      humidity of 90% in the laboratory. Under the same condition, the corrected
      mortalities caused by strains ZJLSP07, ZJLA08 and ZJLP09 were 100%, 92.55% and
      100%, respectively at 9days post-inoculation in the greenhouse. Our findings also
      revealed that these fungal strains infected D. citri using hyphae that penetrated
      deep into the insect tissues. Further, all three strains secreted the enzymes
      proteinases, chitinases and lipases with a potential to destroy insect tissues.
      Interestingly, strain ZJLP09 had an earlier invasion time and the highest levels
      of enzyme activities when compared to the other two strains. These findings have
      expanded the existing pool of entomopathogenic fungi that infect D. citri and can
      be potentially used for the management of D. citri populations. 

PMID- 25593034
TI  - Breast cancer risk in metabolically healthy but overweight postmenopausal women.
AB  - Adiposity is an established risk factor for postmenopausal breast cancer. Recent
      data suggest that high insulin levels in overweight women may play a major role
      in this relationship, due to insulin's mitogenic/antiapoptotic activity. However,
      whether overweight women who are metabolically healthy (i.e., normal insulin
      sensitivity) have elevated risk of breast cancer is unknown. We investigated
      whether overweight women with normal insulin sensitivity [i.e., homeostasis model
      assessment of insulin resistance (HOMA-IR) index, or fasting insulin level,
      within the lowest quartile (q1)] have increased breast cancer risk. Subjects were
      incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's
      Health Initiative (WHI) participants with available fasting insulin and glucose
      levels. In multivariate Cox models, metabolically healthy overweight women,
      defined using HOMA-IR, were not at elevated risk of breast cancer compared with
      metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence
      interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4)
      HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19
      2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using
      fasting insulin to define metabolic health, metabolically unhealthy women
      (insulin q3-4) were at higher risk of breast cancer regardless of whether they
      were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin,
      2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not
      have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64
      1.42) relative to metabolically healthy normal weight women. Metabolic health
      (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more
      useful for breast cancer risk stratification than adiposity per se.

PMID- 25593037
TI  - Pathogenesis, tissue distribution and host response to Rhabdochlamydia
      porcellionis infection in rough woodlouse Porcellio scaber.
AB  - Rhabdochlamydia porcellionis is a known intracellular pathogen in digestive
      glands of the terrestrial isopod crustacean Porcellio scaber. To describe the
      pathogenesis, tissue distribution and host response to R. porcellionis, we
      conducted microscopic observations and localization of infection in tissues by
      Fluorescent In Situ Hybridization (FISH). Digestive glands were confirmed as the
      primary site of infection. From there, R. porcellionis disseminates either
      through the apical membrane of infected cells into the lumen of digestive glands
      and further throughout the digestive tract or into the surrounding hemocoel by
      rupture of the basal membrane and lamina of infected digestive gland cells. Once
      in the hemocoel, R. porcellionis infects hindgut cells, hemocytes and hemopoetic
      tissues while the ventral nerve cord and gonads seem to be devoid of infection
      despite the presence of rhabdochlamydia on the surface of these organs. The host
      response to R. porcellionis includes aggregation of hemocytes around the infected
      cells and formation of multilayered melanized nodules exhibiting endogenous
      fluorescence. The structure of nodules is asymmetric when hemocytes are deposited
      on the basal side of infected gut and digestive glands cells, or symmetric, when
      nodules entrapping clusters of rhabdochlamydiae are deposited on other organs in
      the hemocoel. The study also revealed a high prevalence of infection in P. scaber
      populations (up to 27%) and confirmed its detrimental effect on the host.
      Although agility, behavior and molting cycle of infected animals appear
      unaffected, in the later stages R. porcellionis infection manifests as severe
      damage to the digestive system and decreased feeding, which eventually lead to
      the death of the host organism. 

PMID- 25593038
TI  - Chronic inflammatory mediators enhance prostate cancer development and
      progression.
AB  - Chronic inflammation is postulated to influence prostate cancer progression.
      Preclinical studies have claimed that inflammatory mediators are involved in
      prostate cancer development and therefore suggested these as attractive targets
      for intervention. However, among the many pro-inflammatory mediators, there is no
      consensus regarding the identity of the primary one(s). In clinical studies,
      chronic inflammation has been found in prostate tumor specimens, and tissues
      resected for treatment of benign prostatic hyperplasia (BPH). Although collective
      evidence from molecular, experimental and clinical data suggests that
      inflammation can contribute or promote prostate carcinogenesis, an etiologic link
      has not yet been established. Moreover, the role of chronic inflammation in the
      onset of castration resistant and metastatic disease is unclear. Therefore it is
      important to open a dialog regarding recent findings on how chronic inflammatory
      mediators contribute to prostate cancer progression, and their usefulness to
      prevent disease progression. In this commentary, we assess the current literature
      with respect to chronic inflammation as a potential initiator and promoter of
      prostate carcinogenesis and discuss the prospects for its potential clinical
      applications. 

PMID- 25593039
TI  - Travel risk assessment, advice and vaccinations in immunocompromised travellers
      (HIV, solid organ transplant and haematopoeitic stem cell transplant recipients):
      A review.
AB  - International travellers with immunocompromising conditions such as human
      immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and
      haematopoietic stem cell transplantation (HSCT) are at a significant risk of
      travel-related illnesses from both communicable and non-communicable diseases,
      depending on the intensity of underlying immune dysfunction, travel destinations
      and activities. In addition, the choice of travel vaccinations, timing and
      protective antibody responses are also highly dependent on the underlying
      conditions and thus pose significant challenges to the health-care providers who
      are involved in pre-travel risk assessment. This review article provides a
      framework of understanding and approach to aforementioned groups of
      immunocompromised travellers regarding pre-travel risk assessment and management;
      in particular travel vaccinations, infectious and non-infectious disease risks
      and provision of condition-specific advice; to reduce travel-related mortality
      and morbidity.

PMID- 25593033
TI  - Targeting the eIF4F translation initiation complex: a critical nexus for cancer
      development.
AB  - Elevated protein synthesis is an important feature of many cancer cells and often
      arises as a consequence of increased signaling flux channeled to eukaryotic
      initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment
      phase of translation initiation. In many cellular and preclinical models of
      cancer, eIF4F deregulation results in changes in translational efficiency of
      specific mRNA classes. Importantly, many of these mRNAs code for proteins that
      potently regulate critical cellular processes, such as cell growth and
      proliferation, enhanced cell survival and cell migration that ultimately impinge
      on several hallmarks of cancer, including increased angiogenesis, deregulated
      growth control, enhanced cellular survival, epithelial-to-mesenchymal transition,
      invasion, and metastasis. By being positioned as the molecular nexus downstream
      of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F
      serves as a direct link between important steps in cancer development and
      translation initiation. Identification of mRNAs particularly responsive to
      elevated eIF4F activity that typifies tumorigenesis underscores the critical role
      of eIF4F in cancer and raises the exciting possibility of developing new-in-class
      small molecules targeting translation initiation as antineoplastic agents.

PMID- 25593040
TI  - Prevalence of HIV infection and risky sexual practices among adult males with
      travel-associated Entamoeba histolytica infection in Taiwan, 2006-2013.

PMID- 25593041
TI  - Malaria chemoprophylaxis: a proven public health intervention for international
      travelers.

PMID- 25593042
TI  - Effects of dexamethasone and Mycoplasma bovis on bovine neutrophil function in
      vitro.
AB  - It is well established that exposure either to elevated levels of
      glucocorticoids, or to Mycoplasma bovis (M. bovis), has a negative effect on
      bovine neutrophil function. The objective of this research was to determine
      whether in vitro treatment of bovine neutrophils by M. bovis strains (n=4) and
      glucocorticoids would additively impair phagocyte function. Twenty, healthy,
      dairy cows were enrolled. Whole blood was collected from all cows for neutrophil
      isolation. Phagocytosis and the generation of superoxide anion (O2(-)) were
      tested in vitro by incubation of neutrophils with FITC labeled Escherichia coli
      (E. coli) and cytochrome c after treatment. Treatments included: NM1-4D
      (neutrophils treated with dexamethasone and exposed to one of the four M. bovis
      strains); NM1-4 (neutrophils exposed to one of the four M. bovis strains only);
      ND (neutrophils treated with dexamethasone only); and N (non-treated control
      neutrophils). The overall percentages of neutrophils phagocytizing E. coli were:
      32%, 51%, 37%, and 53% +/- 5.25% for treatments NM1-4D, NM1-4, ND, and N,
      respectively. The overall statistically transformed means of phagocytized E. coli
      per neutrophil were: 1.37, 1.72, 1.33, and 1.67 +/- 0.057 for treatments NM1-4D,
      NM1-4, ND, and N, respectively. The overall statistically transformed means of
      neutrophil O2(-) production were: 8.60, 11.91, 9.01, and 12.21 +/- 0.21
      nmol/10(6) for treatments NM1-4D, NM1-4, ND, and N, respectively. Exposure of
      neutrophils to M. bovis plus dexamethasone had an additive effect on generation
      of reactive oxygen species (p=0.0057), but not on the percentage of neutrophils
      phagocytizing E. coli (p=0.0817) or number of E. coli phagocytized per neutrophil
      (p=0.2946). Only one of the four M. bovis strains had a negative effect on
      neutrophil phagocytic function. Dexamethasone treatment consistently decreased
      neutrophil function as indicated by decreased percentage of neutrophils
      phagocytizing E. coli, decreased number of E. coli phagocytized per neutrophil,
      and decreased neutrophil O2(-) production, compared to controls (p<0.0001).
      Results suggested a synergistic effect of in vitro incubation of glucocorticoids
      and M. bovis on reduction of bovine neutrophil function as measured by generation
      of reactive oxygen species. These findings may explain in part the interaction
      between stressful events and outbreak of Mycoplasma bovis associated bovine
      disease.

PMID- 25593043
TI  - Development and characterization of a monoclonal antibody specific for bovine
      CD209.
AB  - Dendritic cells (DC) play a central role in tailoring the immune response to
      pathogens. Effector activity is mediated through pattern recognition receptors
      (PRRs) that recognize pathogen associated molecular patterns (PAMPS). C-type
      lectin receptors (CLR) comprise a group of PRRs that recognize a broad range of
      pathogens. CD209 (DC-specific ICAM3-grabbing non-integrin, DC-SIGN) is a CLR
      expressed on DC that plays a critical role on DC function and pathogen
      recognition. It facilitates DC migration to peripheral tissues and local lymph
      nodes and mediates T cell activation by binding ICAM-2 (CD102) and ICAM-3 (CD50).
      The absence of monoclonal antibody (mAb) to bovine CD209 has limited the ability
      to characterize the phenotype and function of DC in cattle. To address this issue
      we developed and used a mAb to CD209 to characterize the phenotype of CD209
      expressing cells in bovine blood using flow cytometry. Initial analysis has
      revealed the CD209 positive population in blood is comprised of multiple
      phenotypically defined subsets. 

PMID- 25593044
TI  - The effect of estrogen on the early cytotoxic response to IB virus infection in
      hen oviduct.
AB  - The aim of this study was to determine whether the egg-laying phase and estrogen
      affect the induction of cytotoxic cells in response to avian infectious
      bronchitis (IB) virus at early stage of infection in the oviduct. Attenuated IB
      virus (aIBV group) or its vehicle (control group) was introduced to the oviductal
      magnum lumen of White Leghorn hens in the laying and molting phase, as well as
      molting hens injected with estradiol benzoate (M-EB hens) or corn oil (M-oil
      hens). Oviductal isthmus and uterus were collected 24h after injection. The
      frequency of CD8(+) and TCRgammadelta(+) T cells expression was examined by
      immunohistochemistry, followed by image analysis. The expression of the genes of
      toll-like receptor 7 (TLR7), natural killer cell receptor (BNK), cytotoxic
      substances (granzyme, perforin), and cytokines (CXCL12, CX3CL1, and IFNgamma)
      were examined by real-time polymerase chain reaction analysis. The frequency of
      CD8(+) and TCRgammadelta(+) T cells in the isthmus, and CD8(+) cells in the
      uterus was significantly higher in the aIBV group compared to the control group
      of laying and M-EB hens. The expression of all the genes examined in this study
      in the isthmus, and CX3CL1 and IFNgamma expression in the uterus was
      significantly higher in the aIBV group in the laying and M-EB hens. These results
      suggested that infection with IB virus causes an immune response involving the
      influx of cytotoxic cells and upregulation of cytokines in the isthmus and uterus
      at early stage of infection. This response was stronger during the laying phase
      compared to the molting phase, probably due to the effect of estrogen. 

PMID- 25593045
TI  - Special topic: Ipsilateral femoral neck and shaft fractures--does evidence give
      us the answer?
AB  - Ipsilateral fractures of the femoral neck and shaft are rare, high-energy
      injuries that typically occur in young polytrauma patients. The associated
      fracture of the neck is often vertical in nature and is more frequently non
      displaced than in isolated femoral neck fractures. Historically the diagnosis of
      an associated femoral neck fracture was delayed or missed in approximately one
      third of cases. Studies have shown that detection can be significantly improved
      with the implementation of a protocolized approach to hip imaging in all patients
      with femoral shaft fractures. Prompt recognition of an associated femoral neck
      fracture allows for timely stabilization and may decrease the risks of non-union
      and avascular necrosis. In contrast, failure to recognize a non-displaced or
      minimally displaced associated neck fracture prior to fixation of the shaft can
      lead to displacement, a decrease in neck fixation options, a technically
      challenging secondary procedure and increased risk of long-term sequelae. A vast
      array of treatment strategies have been described for this combined injury.
      Published options range from spica casting to open reduction and internal
      fixation of both fractures and include almost all conceivable combinations in
      between. While timely surgical stabilization is now universally recommended for
      both shaft and neck, no consensus exists as to the most appropriate method of
      fixation for either fracture. Most authors recommend prompt, but not emergent,
      surgery with priority given to anatomic reduction and stabilization of the neck
      fracture by either closed or open methods. Fixation of the shaft fracture follows
      as patient condition allows. The rare nature of this injury makes it very
      challenging to study and most published series' are retrospective with very small
      sample sizes. In short, no scientificallycompelling study is available to
      definitively support any one implant choice or method of stabilzation over
      another for the treatment of associated fractures of the femoral neck and shaft. 

PMID- 25593046
TI  - A novel vibrotactile system for stimulating the glabrous skin of awake freely
      behaving rats during operant conditioning.
AB  - BACKGROUND: Rat skin is innervated by mechanoreceptive fibers similar to those in
      other mammals. Tactile experiments with behaving rats mostly focus on the
      vibrissal system which does not exist in humans. The aim of this study was to
      design and implement a novel vibrotactile system to stimulate the glabrous skin
      of behaving rats during operant conditioning. NEW METHOD: A computer-controlled
      vibrotactile system was developed for various tasks in which the volar surface of
      unrestrained rats' fore- and hindpaws was stimulated in an operant chamber.
      RESULTS: The operant chamber was built from off-the-shelf components. A highly
      accurate electrodynamic shaker with a novel multi-probe design was used for
      generating mechanical displacements. Twenty-five rats were trained for four
      sequential tasks: (A) middle-lever (trial start signal) press, (B) side-lever
      press with an associated visual cue, (C) similar to (B) with the addition of an
      auditory/tactile stimulus, (D) auditory/tactile detection (yes/no) task. Out of 9
      rats which could complete the tactile version of this training schedule, 5 had
      over 70% accuracy in the tactile version of the detection task. COMPARISON WITH
      EXISTING METHODS: Unlike actuators for stimulating whiskers, this system does not
      require a particular head/body alignment and can be used with freely behaving
      animals. CONCLUSIONS: The vibrotactile system was found to be effective for
      conditioning freely behaving rats based on stimuli applied on the glabrous skin.
      However, detection accuracies were lower compared to those in tasks involving
      whisker stimulation reported previously, probably due to differences in cortical
      processing.

PMID- 25593047
TI  - A comparison of region-of-interest measures for extracting whole brain data using
      survival analysis in alcoholism as an example.
AB  - BACKGROUND: Aggregation of functional magnetic resonance imaging (fMRI) data in
      regions-of-interest (ROIs) is required for complex statistical analyses not
      implemented in standard fMRI software. Different data-aggregation measures assess
      various aspects of neural activation, including spatial extent and intensity. NEW
      METHOD: In this study, conducted within the framework of the PREDICT study, we
      compared different aggregation measures for voxel-wise fMRI activations to be
      used as prognostic factors for relapse in 49 abstinent alcohol-dependent
      individuals in an outpatient setting using a cue-reactivity task. We compared the
      importance of the data-aggregation measures as prognostic factors for treatment
      outcomes by calculating the proportion of explained variation. RESULTS AND
      COMPARISON WITH EXISTING METHOD(S): Relapse risk was associated with cue-induced
      brain activation during abstinence in the ventral striatum (VS) and in the
      orbitofrontal cortex (OFC). While various ROI measures proved appropriate for
      using fMRI cue-reactivity to predict relapse, on the descriptive level the most
      "important" prognostic factor was a measure defined as the sum of t-values
      exceeding an individually defined threshold. Data collected in the VS was
      superior to that from other regions. CONCLUSIONS: In conclusion, it seems that
      fMRI cue-reactivity, especially in the VS, can be used as prognostic factor for
      relapse in abstinent alcohol-dependent patients. Our findings suggest that data
      aggregation measures that take both spatial extent and intensity of cue-induced
      brain activation into account make better biomarkers for predicting relapse than
      measures that consider an activation's spatial extent or intensity alone.

PMID- 25593048
TI  - A simple and effective method for building inexpensive infrared equipment used to
      monitor animal locomotion.
AB  - BACKGROUND: Infrared (IR) technology is a flexible and effective way of measuring
      animal locomotion. However, the cost of most commercial IR equipment can limit
      their availability. We have designed an inexpensive and effective replacement for
      commercial IR sensors that can be attached to enclosures to monitor animal
      locomotion. NEW METHOD: IR components were soldered to circuits connected to a
      single microcontroller. These IR components were housed inexpensively using
      plastic tubing and cork discs to further focus and extend detection of the IR
      beam. A standard personal computer recorded data from circuit boards connected to
      an inexpensive interface. This system may be used in a range of lighting
      conditions without requiring readjustment or recalibration. RESULTS: Validation
      of our equipment design was done with male Sprague Dawley rats treated with
      reserpine 22h prior to administration of saline or l-DOPA (125mg/kg). Data was
      collected in eight different measures: horizontal activity, immobile time,
      elevated activity, centre elevated activity, elevation time, elevation bout, and
      repeated and non-repeated movement while elevated. l-DOPA increased horizontal
      movement and all elevated activity excepting elevated movement and centre
      elevated movement, demonstrating selective drug effects. COMPARISON WITH EXISTING
      METHODS: The total cost of our complete IR system (US$517.45) was substantially
      less than the least expensive quote (US$19,666.90) obtained for a commercial IR
      system. CONCLUSIONS: We have successfully designed and constructed a flexible and
      inexpensive IR system to monitor at least eight measures of rodent locomotion at
      a significantly lesser cost than quoted by commercial suppliers.

PMID- 25593049
TI  - Periostin: a novel tissue biomarker correlates with chronicity index and renal
      function in lupus nephritis patients.
AB  - Lupus nephritis (LN) is one of the most serious complications in patients with
      systemic lupus erythematosus (SLE). At present, there is no specific biomarker
      with high sensitivity and renal pathology involvement in use in clinical
      practice. Periostin is an extracellular matrix protein involved in kidney
      development and kidney injury. We performed immunohistochemical analysis for
      periostin and routine staining of 42 kidney tissues from LN patients compared
      with controlled kidney tissues. Activity index, chronicity index and periostin
      staining were evaluated and scored by a renal pathologist. Periglomerular
      staining of periostin was the most predominant finding. Positive periostin
      staining was also observed in areas with fibrosis such as sclerosed glomeruli,
      interstitial fibrosis and fibrous vessels. Moreover, the tubules seemed to be the
      main location for periostin staining. There was a statistically different level
      of periostin staining score between patient and control tissues. Periostin
      staining score also correlated with the chronicity index score of renal pathology
      (r = 0.594, p < 0.001). Periostin was also correlated with worsening renal
      outcomes including serum creatinine, blood urea nitrogen and estimated glomerular
      filtration rate (eGFR). Subgroup analysis within patients with low activity index
      score or low chronicity index score found that there was a statistical difference
      in serum creatinine and eGFR between groups with low and high periostin staining
      scores. We concluded that periostin staining score correlated with chronicity
      index score and renal function in patients with lupus nephritis. 

PMID- 25593050
TI  - A discriminatory mechanical testing performance indicator protocol for hand-mixed
      glass-ionomer restoratives.
AB  - OBJECTIVES: To identify a reproducible and discriminatory mechanical testing
      methodology to act as a performance indicator for hand-mixed glass-ionomer (GI)
      restoratives. METHODS: Groups of 20 (five batches of four) cylinders (6.0+/-0.1
      mm height, 4.0+/-0.1 mm diameter) for compressive fracture strength (CFS) and
      compressive modulus (CM) testing, bars (25.0+/-0.1 mm length, 2.0+/-0.1 mm width,
      2.0+/-0.1 mm thickness) for three-point flexure strength (TFS) and tensile
      flexural modulus (TFM) testing, discs (13.0+/-0.1 mm diameter, 1.0+/-0.1 mm
      thickness and 10.0+/-0.1 mm diameter, 3.10+/-0.03 mm thickness) for biaxial
      flexure strength (BFS) and Hertzian indentation (HI) testing, respectively, were
      prepared using a hand-mixed GI restorative manipulated with 100-20% (in 10%
      increments) of the manufacturers recommended powder content for a constant weight
      of liquid. Data were statistically analyzed at p<0.05, the coefficient of
      variation (CoV) was assessed for the four tests at each powder:liquid mixing
      ratio investigated (n=9) and a Weibull analysis performed on the CFS, TFS and BFS
      data to assess the reliability of the data sets. The failure mode and fracture
      origin of the HI specimens was assessed by fractography. RESULTS: For the hand
      mixed GI restorative, a progressive reduction in the powder content (by 10% for a
      constant weight of liquid) resulted in a progressive linear deterioration
      (p<0.001) in the CFS (R2=0.957), CM (R2=0.961) and TFM (R2=0.982) data. However,
      no linear deterioration (p>0.05) was identified for the TFS (R2=0.572), BFS
      (R2=0.81) and HI (R2=0.234). The CoV and Weibull data identified distinct regions
      -three for the CFS and TFS data and two for the BFS data sets, within the range
      of powder:liquid mixing ratios investigated. Fractographic analysis of HI
      specimens revealed a transition in failure mode from bottom-initiated radial
      cracking to top-initiated cone cracking on reducing the powder content for a
      constant weight of liquid. SIGNIFICANCE: The CFS test is the only discriminatory
      performance indicator for hand-mixed GIs from amongst the four mechanical testing
      approaches (CFS, TFS, BFS and HI) investigated. The CM and TFM represent an
      intrinsic material property independent of specimen dimensions and may be used as
      an adjunct to a mechanical testing approach when investigating hand-mixed GIs.

PMID- 25593051
TI  - Frequency and practice-level variation in inappropriate aspirin use for the
      primary prevention of cardiovascular disease: insights from the National
      Cardiovascular Disease Registry's Practice Innovation and Clinical Excellence
      registry.
AB  - BACKGROUND: Among patients without cardiovascular disease (CVD) and low 10-year
      CVD risk, the risks of gastrointestinal bleeding and hemorrhagic strokes
      associated with aspirin use outweigh any potential atheroprotective benefit.
      According to the guidelines on primary prevention of CVD, aspirin use is
      considered appropriate only in patients with 10-year CVD risk >=6% and
      inappropriate in patients with 10-year CVD risk <6%. OBJECTIVES: The goal of this
      study was to examine the frequency and practice-level variation in inappropriate
      aspirin use for primary prevention in a large U.S. nationwide registry. METHODS:
      Within the National Cardiovascular Disease Registry's Practice Innovation and
      Clinical Excellence registry, we assessed 68,808 unique patients receiving
      aspirin for primary prevention from 119 U.S. practices. The frequency of
      inappropriate aspirin use was determined for primary prevention (aspirin use in
      those with 10-year CVD risk <6%). Using hierarchical regression models, the
      extent of practice-level variation using the median rate ratio (MRR) was
      assessed. RESULTS: Inappropriate aspirin use frequency was 11.6% (7,972 of
      68,808) in the overall cohort. There was significant practice-level variation in
      inappropriate use (range 0% to 71.8%; median 10.1%; interquartile range 6.4%) for
      practices; adjusted MRR was 1.63 (95% confidence interval [CI]: 1.47 to 1.77).
      Results remained consistent after excluding 21,052 women age >=65 years
      (inappropriate aspirin use 15.2%; median practice-level inappropriate aspirin use
      13.8%; interquartile range 8.2%; adjusted MRR 1.61 [95% CI: 1.46 to 1.75]) and
      after excluding patients with diabetes (inappropriate aspirin use 13.9%; median
      practice-level inappropriate aspirin use 12.4%; interquartile range 7.6%;
      adjusted MRR 1.55 [95% CI: 1.41 to 1.67]). CONCLUSIONS: More than 1 in 10
      patients in this national registry were receiving inappropriate aspirin therapy
      for primary prevention, with significant practice-level variations. Our findings
      suggest that there are important opportunities to improve evidence-based aspirin
      use for the primary prevention of CVD.

PMID- 25593052
TI  - The role of the cardiologist in the primary prevention of cardiovascular disease
      with aspirin.

PMID- 25593053
TI  - Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy
      patients.
AB  - BACKGROUND: The role of patient age in the efficacy of mesenchymal stem cell
      (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial. OBJECTIVES: This
      study sought to determine whether the therapeutic effect of culture-expanded MSCs
      persists, even in older subjects. METHODS: Patients with ICM who received MSCs
      via transendocardial stem cell injection (TESI) as part of the TAC-HFT
      (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and
      POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n
      = 30) clinical trials were divided into 2 age groups: younger than 60 and 60
      years of age and older. Functional capacity was measured by 6-min walk distance
      (6MWD) and quality of life using the Minnesota Living With Heart Failure
      Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1 year post
      TESI. Various cardiac imaging parameters, including absolute scar size, were
      compared at baseline and 1 year post-TESI. RESULTS: The mean 6MWD was similar at
      baseline and increased at 1 year post-TESI in both groups: 48.5 +/- 14.6 m (p =
      0.001) for the younger and 35.9 +/- 18.3 m (p = 0.038) for the older participants
      (p = NS between groups). The older group exhibited a significant reduction in
      MLHFQ score (-7.04 +/- 3.54; p = 0.022), whereas the younger than 60 age group
      had a borderline significant reduction (-11.22 +/- 5.24; p = 0.058) from baseline
      (p = NS between groups). Although there were significant reductions in absolute
      scar size from baseline to 1 year post-TESI, the effect did not differ by age.
      CONCLUSIONS: MSC therapy with TESI in ICM patients improves 6MWD and MLHFQ score
      and reduces myocardial infarction size. Importantly, older individuals did not
      have an impaired response to MSC therapy.

PMID- 25593054
TI  - Nucleostemin rejuvenates cardiac progenitor cells and antagonizes myocardial
      aging.
AB  - BACKGROUND: Functional decline in stem cell-mediated regeneration contributes to
      aging associated with cellular senescence in c-kit+ cardiac progenitor cells
      (CPCs). Clinical implementation of CPC-based therapy in elderly patients would
      benefit tremendously from understanding molecular characteristics of senescence
      to antagonize aging. Nucleostemin (NS) is a nucleolar protein regulating stem
      cell proliferation and pluripotency. OBJECTIVES: This study sought to demonstrate
      that NS preserves characteristics associated with "stemness" in CPCs and
      antagonizes myocardial senescence and aging. METHODS: CPCs isolated from human
      fetal (fetal human cardiac progenitor cell [FhCPC]) and adult failing (adult
      human cardiac progenitor cell [AhCPC]) hearts, as well as young (young cardiac
      progenitor cell [YCPC]) and old mice (old cardiac progenitor cell [OCPC]), were
      studied for senescence characteristics and NS expression. Heterozygous knockout
      mice with 1 functional allele of NS (NS+/-) were used to demonstrate that NS
      preserves myocardial structure and function and slows characteristics of aging.
      RESULTS: NS expression is decreased in AhCPCs relative to FhCPCs, correlating
      with lowered proliferation potential and shortened telomere length. AhCPC
      characteristics resemble those of OCPCs, which have a phenotype induced by NS
      silencing, resulting in cell flattening, senescence, multinucleated cells,
      decreased S-phase progression, diminished expression of stemness markers, and up
      regulation of p53 and p16. CPC senescence resulting from NS loss is partially p53
      dependent and is rescued by concurrent silencing of p53. Mechanistically, NS
      induction correlates with Pim-1 kinase-mediated stabilization of c-Myc.
      Engineering OCPCs and AhCPCs to overexpress NS decreases senescent and
      multinucleated cells, restores morphology, and antagonizes senescence, thereby
      preserving phenotypic properties of "stemness." Early cardiac aging with a
      decline in cardiac function, an increase in senescence markers p53 and p16,
      telomere attrition, and accompanied CPC exhaustion is evident in NS+/- mice.
      CONCLUSIONS: Youthful properties and antagonism of senescence in CPCs and the
      myocardium are consistent with a role for NS downstream from Pim-1 signaling that
      enhances cardiac regeneration.

PMID- 25593055
TI  - Stem cells versus senescence: the yin and yang of cardiac health.

PMID- 25593056
TI  - Role of electrophysiological studies in predicting risk of ventricular arrhythmia
      in early repolarization syndrome.
AB  - BACKGROUND: The early repolarization (ER) pattern is associated with an increased
      risk of arrhythmogenic sudden death. However, strategies for risk stratification
      of patients with the ER pattern are not fully defined. OBJECTIVES: This study
      sought to determine the role of electrophysiology studies (EPS) in risk
      stratification of patients with ER syndrome. METHODS: In a multicenter study, 81
      patients with ER syndrome (age 36 +/- 13 years, 60 males) and aborted sudden
      death due to ventricular fibrillation (VF) were included. EPS were performed
      following the index VF episode using a standard protocol. Inducibility was
      defined by the provocation of sustained VF. Patients were followed up by serial
      implantable cardioverter-defibrillator interrogations. RESULTS: Despite a recent
      history of aborted sudden death, VF was inducible in only 18 of 81 (22%)
      patients. During follow-up of 7.0 +/- 4.9 years, 6 of 18 (33%) patients with
      inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%)
      patients who were noninducible experienced recurrent VF (p = 0.93). VF storm
      occurred in 3 patients from the inducible VF group and in 4 patients in the
      noninducible group. VF inducibility was not associated with maximum J-wave
      amplitude (VF inducible vs. VF noninducible; 0.23 +/- 0.11 mV vs. 0.21 +/- 0.11
      mV; p = 0.42) or J-wave distribution (inferior, odds ratio [OR]: 0.96 [95%
      confidence interval (CI): 0.33 to 2.81]; p = 0.95; lateral, OR: 1.57 [95% CI:
      0.35 to 7.04]; p = 0.56; inferior and lateral, OR: 0.83 [95% CI: 0.27 to 2.55]; p
      = 0.74), which have previously been demonstrated to predict outcome in patients
      with an ER pattern. CONCLUSIONS: Our findings indicate that current programmed
      stimulation protocols do not enhance risk stratification in ER syndrome.

PMID- 25593057
TI  - Ventricular fibrillation inducibility in the early repolarization syndrome: we
      still haven't found what we're looking for.

PMID- 25593058
TI  - Alterations in the interactome of serine/threonine protein phosphatase type-1 in
      atrial fibrillation patients.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac
      arrhythmia, yet current pharmacological treatments are limited. Serine/threonine
      protein phosphatase type-1 (PP1), a major phosphatase in the heart, consists of a
      catalytic subunit (PP1c) and a large set of regulatory (R)-subunits that confer
      localization and substrate specificity to the holoenzyme. Previous studies
      suggest that PP1 is dysregulated in AF, but the mechanisms are unknown.
      OBJECTIVES: The purpose of this study was to test the hypothesis that PP1 is
      dysregulated in paroxysmal atrial fibrillation (PAF) at the level of its R
      subunits. METHODS: Cardiac lysates were coimmunoprecipitated with anti-PP1c
      antibody followed by mass spectrometry-based, quantitative profiling of
      associated R-subunits. Subsequently, label-free quantification (LFQ) was used to
      evaluate altered R-subunit-PP1c interactions in PAF patients. R-subunits with
      altered binding to PP1c in PAF were further studied using bioinformatics, Western
      blotting (WB), immunocytochemistry, and coimmunoprecipitation. RESULTS: A total
      of 135 and 78 putative PP1c interactors were captured from mouse and human
      cardiac lysates, respectively, including many previously unreported interactors
      with conserved PP1c docking motifs. Increases in binding were found between PP1c
      and PPP1R7, cold-shock domain protein A (CSDA), and phosphodiesterase type-5A
      (PDE5A) in PAF patients, with CSDA and PDE5A being novel interactors validated by
      bioinformatics, immunocytochemistry, and coimmunoprecipitation. WB confirmed that
      these increases in binding cannot be ascribed to their changes in global protein
      expression alone. CONCLUSIONS: Subcellular heterogeneity in PP1 activity and
      downstream protein phosphorylation in AF may be attributed to alterations in PP1c
      R-subunit interactions, which impair PP1 targeting to proteins involved in
      electrical and Ca(2+) remodeling. This represents a novel concept in AF
      pathogenesis and may provide more specific drug targets for treating AF.

PMID- 25593059
TI  - Affinity proteomics for phosphatase interactions in atrial fibrillation.

PMID- 25593061
TI  - Catheter ablation of atrial fibrillation: how to modify the substrate?
AB  - A frequent need for re-ablations and limited overall success rates are still
      major limitations of catheter ablation procedures for the treatment of atrial
      fibrillation (AF). These limitations include not only the durability of the
      pulmonary vein isolation (PVI) lines, but also the pathophysiological
      understanding of the arrhythmia's substrate. Long-term single procedure success
      rates in non-paroxysmal AF are disappointingly low for current stepwise ablation
      approaches adding the placement of linear lines and electrogram-based ablation
      after circumferential PVI isolation. In the future, substrate modification in AF
      ablation should move toward individualized patient-tailored ablation procedures.
      Magnetic resonance imaging could play a major role for noninvasively describing
      the localization and extent of fibrotic areas. Specific new strategies that could
      be used include precise localization and ablation of rotors that maintain the
      arrhythmia using multielectrode mapping during AF and box isolation of fibrotic
      areas guided by electroanatomic voltage mapping during sinus rhythm. 

PMID- 25593062
TI  - Follow-up on ABIM maintenance of certification.

PMID- 25593063
TI  - A praise for reviewers: how do we reward them?

PMID- 25593064
TI  - Moonlighting: pros and cons for fellows.

PMID- 25593065
TI  - Acute myocardial infarction: a national analysis of the weekend effect over time.

PMID- 25593066
TI  - Ventricular tachycardia and tuberculous lymphadenopathy: sign of myocardial
      tuberculosis?

PMID- 25593060
TI  - Remote ischemic conditioning.
AB  - In remote ischemic conditioning (RIC), brief, reversible episodes of ischemia
      with reperfusion in one vascular bed, tissue, or organ confer a global protective
      phenotype and render remote tissues and organs resistant to ischemia/reperfusion
      injury. The peripheral stimulus can be chemical, mechanical, or electrical and
      involves activation of peripheral sensory nerves. The signal transfer to the
      heart or other organs is through neuronal and humoral communications. Protection
      can be transferred, even across species, with plasma-derived dialysate and
      involves nitric oxide, stromal derived factor-1alpha, microribonucleic acid-144,
      but also other, not yet identified factors. Intracardiac signal transduction
      involves: adenosine, bradykinin, cytokines, and chemokines, which activate
      specific receptors; intracellular kinases; and mitochondrial function. RIC by
      repeated brief inflation/deflation of a blood pressure cuff protects against
      endothelial dysfunction and myocardial injury in percutaneous coronary
      interventions, coronary artery bypass grafting, and reperfused acute myocardial
      infarction. RIC is safe and effective, noninvasive, easily feasible, and
      inexpensive.

PMID- 25593067
TI  - Increased mortality by digoxin in patients with atrial fibrillation?

PMID- 25593068
TI  - Reply: increased mortality by digoxin in patients with atrial fibrillation?

PMID- 25593069
TI  - Patent foramen ovale and paradoxical systemic embolism: can we determine high
      risk characteristics by echocardiography?

PMID- 25593070
TI  - Reply: patent foramen ovale and paradoxical systemic embolism: can we determine
      high-risk characteristics by echocardiography?

PMID- 25593073
TI  - Experienced nurses' use of non-pharmacological approaches comprise more than
      relief from pain: letter to the editor.

PMID- 25593071
TI  - BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis.
AB  - The prognostic value of the BRAFV600E mutation, resulting in poor clinical
      outcomes of papillary thyroid carcinoma, has been generally confirmed. However,
      the association of BRAFV600E with aggressive clinical behaviors of papillary
      thyroid microcarcinoma (PTMC) has not been firmly established in individual
      studies. We performed this meta-analysis to examine the relationship between
      BRAFV600E mutation and the clinicopathological features of PTMC. We conducted a
      systematic search in PubMed, EMBASE, and the Cochrane library for relevant
      studies. We selected all the studies that reported clinicopathological features
      of PTMC patients with information available on BRAFV600E mutation status.
      Nineteen studies involving a total of 3437 patients met these selection criteria
      and were included in the analyses. The average prevalence of the BRAFV600E
      mutation was 47.48%, with no significant difference with respect to patient sex
      (male versus female) and age (younger than 45 years versus 45 years or older).
      Compared with the WT BRAF gene, the BRAFV600E mutation was associated with tumor
      multifocality (odds ratio (OR) 1.38; 95% CI, 1.04-1.82), extrathyroidal extension
      (OR 3.09; 95% CI, 2.24-4.26), lymph node metastases (OR 2.43; 95% CI, 1.28-4.60),
      and advanced stage (OR 2.39; 95% CI, 1.38-4.15) of PTMC. Thus, our findings from
      this large meta-analysis definitively demonstrate that BRAFV600E-mutation
      positive PTMC are more likely to manifest with aggressive clinicopathological
      characteristics. In appropriate clinical settings, testing for the BRAFV600E
      mutation is likely to be useful in assisting the risk stratification and
      management of PTMC. 

PMID- 25593074
TI  - Infliximab, methotrexate and their combination for the treatment of rheumatoid
      arthritis: a systematic review and meta-analysis.
AB  - We performed a systematic review to evaluate the efficacy and safety of
      infliximab + methotrexate (IFX + MTX) regimens versus MTX alone or in combination
      with other disease-modifying anti-rheumatic drugs (DMARDs). We searched through
      major databases, the grey literature and did a manual search. Two independent
      reviewers conducted the selection, data extraction and analysis of the quality of
      the studies. Meta-analysis was conducted using Review Manager((r)) 5.1 software.
      Nine trials were included. The mean modified Jadad score was 4.4, but only one
      study showed low risk of bias. IFX + MTX regimen presented better responses in
      clinical outcomes of ACR and DAS28 by up to 54 weeks, and of radiographic
      progression by up to 104 weeks. Withdrawals due to lack of efficacy was lower in
      the IFX + MTX group. No significant difference in adverse events was observed.
      The IFX + MTX combination is more effective than treatment with MTX alone or
      DMARDs combination. This regimen presented good tolerability in patients
      previously treated with DMARDs, not treated with MTX or with insufficient
      responses to MTX. The efficacy of IFX + MTX is noted primarily during initial
      periods of treatment. High doses of IFX were as effective as the standard dose,
      but with possible higher risk of serious infections. Therefore, we advise
      clinicians to use the standard dose of IFX 3 mg/kg every 8 weeks. 

PMID- 25593076
TI  - The challenge of defining mesenchymal stromal cell potency assays and their
      potential use as release criteria.

PMID- 25593075
TI  - A Photobacterium sp. alpha2-6-sialyltransferase (Psp2,6ST) mutant with an
      increased expression level and improved activities in sialylating Tn antigens.
AB  - In order to improve the catalytic efficiency of recombinant Photobacterium sp. JT
      ISH-224 alpha2-6-sialyltransferase Psp2,6ST(15-501)-His6 in sialylating alpha
      GalNAc-containing acceptors for the synthesis of tumor-associated carbohydrate
      antigens sialyl Tn (STn), protein crystal structure-based mutagenesis studies
      were carried out. Among several mutants obtained by altering the residues close
      to the acceptor substrate binding pocket, mutant A366G was shown to improve the
      sialyltransferase activity of Psp2,6ST(15-501)-His6 toward alpha-GalNAc
      containing acceptors by 21-115% without significantly affecting its sialylation
      activity to beta-galactosides. Furthermore, the expression level was improved
      from 18-40 mg L(-1) for the wild-type enzyme to 72-110 mg L(-1) for the A366G
      mutant. In situ generation of CMP-sialic acid in a one-pot two-enzyme system was
      shown effective in overcoming the high donor hydrolysis of the enzyme. Mutant
      A366G performed better than the wild-type Psp2,6ST(15-501)-His6 for synthesizing
      Neu5Acalpha2-6GalNAcalphaOSer/Thr STn antigens.

PMID- 25593077
TI  - Cryopreservation does not alter main characteristics of Good Manufacturing
      Process-grade human multipotent mesenchymal stromal cells including
      immunomodulating potential and lack of malignant transformation.
AB  - BACKGROUND AIMS: The immunomodulating capacity of multipotent mesenchymal stromal
      cells (MSCs) qualifies them as a therapeutic tool in several diseases. However,
      repeated transplantation with products of reproducible characteristics may be
      required. This could be achieved with cryopreserved aliquots of Good
      Manufacturing Practice (GMP)-grade MSCs. However, the impact of cryopreservation
      on the characteristics of GMP-MSCs is ill defined. METHODS: We produced fresh and
      cryopreserved MSCs from human donors with a xenogen-free GMP protocol.
      Immunogenicity and immunomodulating capacity were tested in co-culture with
      putative recipient-specific peripheral blood mononuclear cells (PBMCs). Risk of
      malignant transformation was assessed in vitro and in vivo. RESULTS:
      Cryopreservation had no impact on viability and consensus criteria of MSCs. In co
      culture with PBMCs, MSCs showed low immunogenicity and suppressed mitogen
      stimulated proliferation of PBMC irrespective of cryopreservation. Cytogenetic
      aberrations were not observed consistently in fresh and cryopreserved products,
      and no signs of malignant transformation occurred in functional assays. MSC
      products from an elderly pretreated donor showed reduced functional quality, but
      imminent failure of functional criteria could be detected by an increased
      population doubling time in early passages. DISCUSSION: This study is the first
      systematic analysis on cryopreservation of xenogen-free human bone marrow-derived
      GMP-MSCs. The data support that cryopreservation does not alter the
      characteristics of the cells and thus may allow the generation of products for
      serial transplantation. In addition, the protocol allowed early detection of MSC
      products with low functional capacity.

PMID- 25593078
TI  - Effect of umbilical cord mesenchymal stromal cells on motor functions of
      identical twins with cerebral palsy: pilot study on the correlation of efficacy
      and hereditary factors.
AB  - BACKGROUND AIMS: The objective of this study was to compare the impact of
      umbilical cord-derived mesenchymal stromal cell (UCMSC) transplantation on the
      motor functions of identical twins with cerebral palsy (CP) and to analyze the
      correlation between the efficacy and hereditary factors. METHODS: Eight pairs (16
      individuals) of identical twins with CP were recruited and received allogenic
      UCMSC transplantation by means of subarachnoid injection. The gross motor
      function measure (GMFM) and the fine motor function measure (FMFM) were performed
      before and 1 and 6 months after the treatment to analyze the results of
      individuals before and after the therapy, between two individuals of an identical
      twin and among twin pairs. Repeated-measured data variance was used to analyze
      the GMFM and FMFM scores of patients before and 1 and 6 months after the therapy.
      RESULTS: Eight pairs (16 individuals) of children with CP had significant
      improvement in the GMFM at the end of the 1st and 6th months after the therapy
      compared with that before the therapy, whereas the amelioration of the FMFM was
      not statistically significant. The improvements in motor functions between two
      individuals of an identical twin but not among twin pairs were correlated.
      CONCLUSIONS: UCMSC transplantation significantly improves GMFM in children with
      CP; motor function improvements in the GMFM between two individuals of an
      identical twin were closely correlated, but improvements among twin pairs were
      not correlated. We hypothesize that hereditary factors contribute to the
      mechanisms of UCMSC transplantation in motor function improvement in children
      with CP.

PMID- 25593079
TI  - Intrathecal injection of CD133-positive enriched bone marrow progenitor cells in
      children with cerebral palsy: feasibility and safety.
AB  - BACKGROUND AIMS: Recent studies have proposed that cellular transplantation may
      have some regenerative and functional efficacy in the treatment of cerebral palsy
      (CP); however, much remains to be understood regarding its safety, feasibility
      and efficacy. This study was initiated to evaluate the safety of autologous bone
      marrow-derived CD133(+) cell intrathecal injection. METHODS: Children (n = 12),
      aged 4 to 12 years, who were diagnosed with different types of CP underwent BM
      aspiration. CD133(+) cells were enriched from the BM samples and intrathecally
      injected. The Gross Motor Function Measure (GMFM-66), Gross Motor Function
      Classification System (GMFCS), UK FIM+FAM, Functional Independence Measure (FIM)
      and Functional Assessment Measure (FAM) were assessed at baseline and 6 months
      after the procedure. Patients' ability to balance was measured by the Berg
      Balance Scale (BBS), and severity of spasticity was evaluated by the Modified
      Ashworth Scale. Magnetic resonance imaging was done at baseline and 6 months
      after therapy. This study was registered in ClinicalTrials.gov (NCT01404663).
      RESULTS: There were no adverse events detected by clinical and laboratory tests
      or imaging studies, with the exception of a seizure in 1 patient. A significant
      improvement was observed 6 months after cell transplantation versus baseline
      according to GMFM, GMFCS, FIM+FAM, Ashworth Scale, and BBS outcomes. CONCLUSIONS:
      Subarachnoid injection of CD133-positive enriched bone marrow progenitor cells in
      children with CP is a safe approach. The results suggest a possible short-term
      improvement in neurological function.

PMID- 25593081
TI  - ALA-mediated photodynamic effect on apoptosis induction and secretion of
      macrophage migration inhibitory factor (MIF) and of monocyte chemotactic protein
      (MCP-1) by colon cancer cells in normoxia and in hypoxia-like conditions in
      vitro.
AB  - BACKGROUND: Photodynamic therapy (PDT) reveals immune modulatory effect. The aim
      of the study was to evaluate the influence of 5-aminolevulinic acid (ALA)
      mediated photodynamic effect on secretory activity (MIF, MCP-1) of colon cancer
      cells in vitro both in normoxia and in hypoxia-like conditions. METHODS: Two
      colon cancer cell lines differing in malignancy potential: SW480 (lower grade)
      and SW620 (higher grade) were used. MCP-1 and MIF concentrations in supernatants
      of cells cultures after pretreatment with ALA at concentrations of 500, 1000 and
      1500MUM and irradiation with incoherent light (lambda=600-720nm) at fluences of
      10, 30 and 60J/cm(2), using Bio-Plex ProTM Assay kit and Bio-Plex Suspension
      Array System apparatus, were measured. RESULTS: The SW620 cells were more
      susceptible to ALA-mediated phototoxic effect than SW480 one, however this effect
      may be partly abolished in hypoxia-like condition. In the case of SW480 cell
      line, no influence of hypoxia-like conditions on cell susceptibility to ALA
      mediated photodynamic effect was found. The MIF concentration increased, contrary
      to MCP-1 one which decreased after ALA-mediated photodynamic action in both cell
      lines. No difference between cytokines concentration in supernatant from cells
      cultures in normoxia or hypoxia-like conditions was observed. CONCLUSIONS:
      Detected reduction in MCP-1 secretion appears to be advantage because of tumor's
      growth limiting but an increase in the secretion of MIF, which is responsible for
      stimulation of tumor cells proliferation, is an unfavorable effect. These results
      may be explained by the fact that the used cancer cell lines differ from each
      other in cancer stage.

PMID- 25593082
TI  - [Mandibular advancement device for obstructive sleep apnea treatment in adults.
      July 2014].

PMID- 25593080
TI  - Fibroblast activation protein alpha in tumor microenvironment: recent progression
      and implications (review).
AB  - Accumulated evidence has demonstrated that the microenvironment of a given tumor
      is important in determining its drug resistance, tumorigenesis, progression and
      metastasis. These microenvironments, like tumor cells, are vital targets for
      cancer therapy. The cross-talk between tumor cells and cancer-associated
      fibroblasts (CAFs, alternatively termed activated fibroblasts) is crucial in
      regulating the drug resistance, tumorigenesis, neoplastic progression,
      angiogenesis, invasion and metastasis of a tumor. Fibroblast activation protein
      alpha (FAPalpha) is a transmembrane serine protease and is highly expressed on
      CAFs present in >90% of human epithelial neoplasms. FAPalpha activity, alongside
      that of gelatinase and type I collagenase, has become increasingly important in
      cancer therapy due to its effectiveness in modulating tumor behavior. In this
      review, recent progression in the knowledge of the role of FAPalpha in tumor
      microenvironments is discussed.

PMID- 25593083
TI  - Health-related quality of life and sense of coherence among Polish immigrants in
      Germany and indigenous Poles.
AB  - Immigrants are faced with several impediments in the host country that may affect
      their quality of life (QoL), but little is known about the impact of these
      stressors as well as about the protective role of sense of coherence (SoC) in the
      context of Polish immigration to Germany. Health Related QoL (Short Form Health
      Survey SF-36) and SoC (Sense of Coherence Scale SOC-29) were assessed in a total
      sample consisting of 511 participants aged between 18 and 84 years (260 Polish
      immigrants in Germany and 251 indigenous Poles). Polish immigrants reported a
      significantly lower mental and physical health-related QoL than the German norm
      population, but they were comparable to native Poles. This result remained the
      same when the model was adjusted for age but physical health status was better
      for immigrants compared with indigenous Poles. Both groups scored significantly
      lower for SoC than Germans, but did not differ from each other. The main
      differences concerning the examined variables were with respect to the German
      norm population and are putatively shaped by culture. 

PMID- 25593084
TI  - Montane and coastal species diversification in the economically important Mexican
      grasshopper genus Sphenarium (Orthoptera: Pyrgomorphidae).
AB  - The genus Sphenarium (Pyrgomorphidae) is a small group of grasshoppers endemic to
      Mexico and Guatemala that are economically and culturally important both as a
      food source and as agricultural pests. However, its taxonomy has been largely
      neglected mainly due to its conserved interspecific external morphology and the
      considerable intraspecific variation in colour pattern of some taxa. Here we
      examined morphological as well as mitochondrial and nuclear DNA sequence data to
      assess the species boundaries and evolutionary history in Sphenarium. Our
      morphological identification and DNA sequence-based species delimitation, carried
      out with three different approaches (DNA barcoding, general mixed Yule-coalescent
      model, Bayesian species delimitation), all recovered a higher number of putative
      species of Sphenarium than previously recognised. We unambiguously delimit seven
      species, and between five and ten additional species depending on the data/method
      analysed. Phylogenetic relationships within the genus strongly support two main
      clades, one exclusively montane, the other coastal. Divergence time estimates
      suggest late Miocene to Pliocene ages for the origin and most of the early
      diversification events in the genus, which were probably influenced by the
      formation of the Trans-Mexican Volcanic Belt. A series of Pleistocene events
      could have led to the current species diversification in both montane and coastal
      regions. This study not only reveals an overlooked species richness for the most
      popular edible insect in Mexico, but also highlights the influence of the dynamic
      geological and climatic history of the region in shaping its current diversity. 

PMID- 25593085
TI  - 3,4-Methylenedioxy-beta-nitrostyrene inhibits adhesion and migration of human
      triple-negative breast cancer cells by suppressing beta1 integrin function and
      surface protein disulfide isomerase.
AB  - Triple negative breast cancer (TNBC) exhibits an aggressive clinical course by
      high metastatic potential. It is known that integrin-mediated cell adhesion and
      migration are important for cancer metastasis. In the present study, a synthetic
      compound, 3, 4-methyenedioxy-beta-nitrostyrene (MNS), significantly inhibited
      adhesion of TNBC cell lines to different extracellular matrix (ECM) components.
      The antimetastatic capacity of MNS was also observed through reducing TNBC cells
      migration and invasion without affecting cell viability. Confocal microscopy
      revealed that MNS disrupted the formation of focal adhesion complex and actin
      stress fiber networks. Consistent with this finding, MNS inhibited
      phosphorylation of focal adhesion kinase (FAK) and paxillin as detected by
      Western blot analysis. In exploring the underlying mechanism, we found that MNS
      inhibited phosphorylation of FAK as a result of reducing beta1 integrin
      activation and clustering. A cell-impermeable dithiol reagent, 2, 3
      dimercaptopropane-1-sulfonic acid abrogated all of MNS's actions, indicating that
      MNS may react with thiol groups of cell surface proteins that are involved in
      regulation of beta1 integrin function as well as cell adhesion and migration.
      Cell surface protein disulfide isomerase (PDI) has been reported to be essential
      for the affinity modulation of beta integrins. We also demonstrated that MNS
      inhibited PDI activity both in a pure enzyme system and in intact cancer cells.
      Taken together, our results suggest that MNS inhibits in vitro metastatic
      properties of TNBC cells through suppression of beta1 integrin activation and
      focal adhesion signaling. Moreover, inhibition of surface PDI may contribute, at
      least in part, to the actions of MNS. These results suggest that MNS has a
      potential to be developed as an anticancer agent for treatment of TNBC. 

PMID- 25593086
TI  - Harmony in discord.

PMID- 25593087
TI  - Rethinking COPD care in the UK: who cares?

PMID- 25593088
TI  - Movement towards personalised medicine in the ICU.

PMID- 25593089
TI  - What's weighing down heliox?

PMID- 25593092
TI  - Real engagement with communities.

PMID- 25593091
TI  - Household air pollution: a call to action.

PMID- 25593093
TI  - Corrections.

PMID- 25593094
TI  - Corrections.

PMID- 25593095
TI  - Synthesis and in vitro biological evaluation of 2-(phenylcarbamoyl)phenyl 4
      substituted benzoates.
AB  - Based on the previously described antimicrobial activity of salicylanilide
      derivatives, we designed and synthesized novel 2-(phenylcarbamoyl)phenyl 4
      substituted benzoates. The most active salicylanilides were selected for
      esterification by various 4-substituted benzoic acids. These compounds were
      evaluated in vitro against Mycobacterium tuberculosis, including multidrug
      resistant strains, nontuberculous mycobacteria (Mycobacterium avium and
      Mycobacterium kansasii), and eight bacterial and fungal strains. We also
      investigated the cytostatic and cytotoxic actions of the esters. The minimum
      inhibitory concentrations (MICs) against mycobacteria ranged from 0.125 to 8MUM.
      Interestingly, the drug-resistant strains exhibited the highest susceptibility
      without any cross-resistance with established drugs. 4-Bromo-2-[4
      (trifluoromethyl)phenylcarbamoyl]phenyl 4-nitrobenzoate showed the most potent
      inhibition with MIC values ranging from 0.25 to 2MUM. Gram-positive bacteria,
      including methicillin-resistant Staphylococcus aureus, were inhibited by two
      derivatives with MIC values of at least 0.49MUM, whereas Gram-negative bacteria
      and most of the tested fungi did not display any marked susceptibility. Benzoates
      exhibited no cytotoxicity at concentrations up to 50MUM but most caused
      significant cytostasis with IC50 values lower than 10MUM. Some cytotoxicity-based
      selectivity indexes for drug-susceptible and drug-resistant M. tuberculosis as
      well as Staphylococci were higher than 100. These values indicate that some of
      these derivatives are promising candidates for future research. 

PMID- 25593097
TI  - Quinoline-based antimalarial hybrid compounds.
AB  - Quinoline-containing compounds, such as quinine and chloroquine, have a long
      standing history as potent antimalarial agents. However, the increasing
      resistance of the Plasmodium parasite against these drugs and the lack of
      licensed malaria vaccines have forced chemists to develop synthetic strategies
      toward novel biologically active molecules. A strategy that has attracted
      considerable attention in current medicinal chemistry is based on the conjugation
      of two biologically active molecules into one hybrid compound. Since quinolines
      are considered to be privileged antimalarial building blocks, the synthesis of
      quinoline-containing antimalarial hybrids has been elaborated extensively in
      recent years. This review provides a literature overview of antimalarial hybrid
      molecules containing a quinoline core, covering publications between 2009 and
      2014. 

PMID- 25593096
TI  - Potency enhancement of the kappa-opioid receptor antagonist probe ML140 through
      sulfonamide constraint utilizing a tetrahydroisoquinoline motif.
AB  - Optimization of the sulfonamide-based kappa opioid receptor (KOR) antagonist
      probe molecule ML140 through constraint of the sulfonamide nitrogen within a
      tetrahydroisoquinoline moiety afforded a marked increase in potency. This
      strategy, when combined with additional structure-activity relationship
      exploration, has led to a compound only six-fold less potent than norBNI, a
      widely utilized KOR antagonist tool compound, but significantly more
      synthetically accessible. The new optimized probe is suitably potent for use as
      an in vivo tool to investigate the therapeutic potential of KOR antagonists. 

PMID- 25593098
TI  - Development of 1,3-diphenyladamantane derivatives as nonsteroidal progesterone
      receptor antagonists.
AB  - Nonsteroidal progesterone receptor (PR) full antagonists are needed as tools for
      elucidating the physiological functions of PR and as candidates for treatment of
      various diseases. We designed and synthesized 1,3-diphenyladamantane derivatives,
      and investigated their PR-antagonistic activity in comparison with our recently
      developed boron cluster-based PR antagonists. Among the synthesized adamantane
      derivatives, compound 9a exhibited the most potent PR-antagonistic activity
      (IC50: 25nM) and showed high binding affinity for the PR ligand-binding domain,
      comparable with that of the boron cluster-based PR antagonists. These results
      suggest that disubstituted adamantane, like the boron cluster m-carborane, is a
      promising hydrophobic pharmacophore for further structural development of
      nonsteroidal PR antagonists. 

PMID- 25593099
TI  - Development of potent dopamine-norepinephrine uptake inhibitors (DNRIs) based on
      a (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol
      molecular template.
AB  - Current therapy of depression is less than ideal with remission rates of only 25
      35% and response rates of 45-60%. It has been hypothesized that a dysfunctional
      dopaminergic system in the mesocorticolimbic pathway in depressive disorder may
      lead to development of anhedonia associated with loss of pleasure and interest
      along with loss of motivation. The current antidepressants do not address
      dopamine dysfunction which might explain their low efficacy. In this report, we
      have described an SAR study on our pyran-based triple reuptake inhibitors (TRIs)
      which are being investigated as the next-generation antidepressants. In the
      present work we demonstrate that our lead TRIs can be modified with appropriate
      aromatic substitutions to display a highly potent SSRI profile for compounds 2a
      and 4a (Ki (SERT); 0.71 and 2.68nM, respectively) or a potent DNRI profile for
      compounds 6b and 6h (Ki (DAT/NET); 8.94/4.76 and 13/7.37nM, respectively).
      Compounds 4g-4i exhibited potencies at all three monoamine transporters. The
      results provide insights into the structural requirements for developing
      selective dual- and triple-uptake inhibitors from a unique pyran molecular
      template for an effective management of depression and related disorders. 

PMID- 25593100
TI  - Trajectories of Symptom Occurrence and Severity From Before Through Five Months
      After Lung Cancer Surgery.
AB  - CONTEXT: Limited information is available about lung cancer patients' symptoms in
      the pre- and postoperative periods. OBJECTIVES: Study purposes were to evaluate
      for changes in symptom occurrence and severity from the preoperative period to
      five months after surgery and to evaluate for predictors of the occurrence and
      trajectories of these symptoms. METHODS: Patients completed the Memorial Symptom
      Assessment Scale before and at one and five months after surgery. Changes in the
      six most common physical symptoms and the most common psychological symptom were
      evaluated using multilevel growth mixture modeling. Age, gender, comorbidity, and
      receipt of adjuvant chemotherapy were included as covariates in the conditional
      models for symptom occurrence and severity. RESULTS: The total number of symptoms
      increased significantly from the preoperative to the one month assessment. At
      five months, the number of symptoms was lower than at one month but significantly
      higher than at the preoperative assessment. The occurrence of five of the
      symptoms (i.e., pain, lack of energy, shortness of breath, feeling drowsy, and
      worrying) increased significantly from before through the first month after
      surgery and then decreased over time. Cough and difficulty sleeping persisted
      over the five months of the study. In general, the effect of the four covariates
      was to increase patients' overall symptom burden. CONCLUSION: Changes in the
      occurrence and severity of these seven symptoms were variable. All seven symptoms
      occurred at relatively high rates and were of moderate severity. Findings can be
      used to identify patients who are at higher risk for more severe symptoms.

PMID- 25593101
TI  - Independent Validation of the Japanese Version of the EORTC QLQ-C15-PAL for
      Patients With Advanced Cancer.
AB  - CONTEXT: Although the psychometric properties of the Japanese version of the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) have been examined
      previously, that study had several limitations, for example, small sample size.
      OBJECTIVES: To examine the validity and reliability, including test-retest
      reliability, of the Japanese version of EORTC QLQ-C15-PAL for cancer patients
      with metastasis or recurrence. METHODS: A cross-sectional anonymous questionnaire
      was administered to cancer patients who were being treated on an oncology
      inpatient ward, in an oncology outpatient clinic, and in seven inpatient
      palliative units in Japan, from August 2007 to March 2008. RESULTS: Data from a
      total of 312 cancer patients were analyzed. The proportion of missing values was
      less than 4% for all items. The factor structure was reproduced identically with
      the original EORTC QLQ-C15-PAL, English version. The correlation of subscales
      showed a reasonable matrix. Cronbach's alpha coefficients were 0.76 to 0.86, and
      intraclass correlation coefficients, which indicate test-retest reliability,
      ranged from 0.52 to 0.77. All subscales, especially physical functioning,
      fatigue, and pain, were significantly correlated with self-reported Eastern
      Cooperative Oncology Group performance status. CONCLUSION: The Japanese version
      of EORTC QLQ-C15-PAL has sufficient validity, acceptable reliability, and
      feasibility for patients with advanced cancer.

PMID- 25593102
TI  - Spinocerebellar ataxia 36 (SCA36): "Costa da Morte ataxia".
AB  - INTRODUCTION-OBJECTIVE: To describe the history of the discovery of SCA36 and
      review knowledge of this entity, which is currently the most prevalent hereditary
      ataxia in Galicia (Spain) owing to a founder effect. DEVELOPMENT: SCA36 is an
      autosomal dominant hereditary ataxia with late onset and slow progression. It
      presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor
      neuron impairment (tongue atrophy with denervation, discrete pyramidal signs).
      SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da
      Morte ataxia). The condition is caused by a genetic mutation (intronic
      hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome
      20 (20p13). Magnetic resonance image study initially shows cerebellar vermian
      atrophy that subsequently extends to the rest of the cerebellum and finally to
      the pontomedullary region of the brainstem without producing white matter
      lesions. Peripheral nerve conduction velocities are normal, and sensorimotor
      evoked potential studies show delayed conduction of stimuli to lower limbs. In
      patients with hearing loss, audiometric studies show a drop of >40dB in
      frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show
      lack of waves I and II. CONCLUSIONS: Costa da Morte ataxia or SCA36 is the most
      prevalent SCA in the Spanish region of Galicia. Given the region's history of
      high rates of emigration, new cases may be diagnosed in numerous countries,
      especially in Latin America. Genetic studies are now available to patients and
      asymptomatic carriers. Since many people are at risk for this disease, we will
      continue our investigations aimed at elucidating the underlying pathogenic
      molecular mechanisms and discovering effective treatment.

PMID- 25593103
TI  - Characteristics of a cluster-randomized phase IV human papillomavirus vaccination
      effectiveness trial.
AB  - High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal
      cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant
      is very efficacious against hrHPV associated precancers but the herd effects of
      different vaccination scenarios are not known. Our cluster randomized trial
      (NCT00534638) assesses the overall and herd effects of vaccinating girls vs.
      girls and boys. In two school-years (2007-2008 and 2008-2009) we invited 80,272
      1992-1995 born early adolescents to a CRT in 33 communities a priori stratified
      by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities
      90% of participating girls and boys were assigned to receive HPV-16/18 vaccine,
      in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine -
      boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C
      communities all were assigned to receive HBV-vaccine. Prevalence of HPV in
      vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment
      resulted in equal enrolment of four birth cohorts (born 1992-1995) comprising
      altogether 32,175 (40% response) early adolescents: 20,514 girls (50.5-53.0%
      response by arm) and 11,661 boys (21.9-31.6%% response by arm). At the age of 15
      years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were
      living at, and during the week-ends 1.3-1.6% stayed outside, the study site
      communities. Smoking habit and alcohol consumption were similar in the different
      trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6
      years), and sexual behaviour (among those <25%, who had had sexual debut) did not
      differ by arm: mean-age at the sexual debut 14.3 and 14.4 in girls and boys, and
      proportions of those with multiple (>=5) life-time sexual partners (6.5-7.5%) at
      the age of 15 years. Uniform residential, life-style and sexual behaviour
      characteristics indicate successful randomization/enrolment of the CRT. Our CRT
      will verify modelled predictions on up to 31% herd effect of vaccinating both
      girls and boys with moderate vaccine coverage - quantifying overall effectiveness
      of different strategies which will soon guide how to implement HPV vaccination. 

PMID- 25593104
TI  - Measuring the effects of pneumococcal conjugate vaccine (PCV7) on Streptococcus
      pneumoniae carriage and antibiotic resistance: the Palestinian-Israeli
      Collaborative Research (PICR).
AB  - BACKGROUND: The Palestinian-Israeli Collaborative Research (PICR) cross-conflict
      setting provided a unique opportunity to study overall and indirect effects of
      pneumococcal conjugate vaccine (PCV7), in two closely related Palestinian
      populations governed by two distinct health authorities with distinct vaccination
      policies. Here, PCV7 effects on pneumococcal carriage, serotype distribution and
      antibiotic resistance are reported. METHODS: Annual cross-sectional surveys of
      pneumococcal carriage were performed during 2009-2011 among Palestinian children
      (<=5 years) (a) under Palestinian-Authority (PA) health policy (Ramallah, Nablus
      and Bethlehem), where PCV7 was unlicensed (b) under Israeli health policy (East
      Jerusalem (EJ)) where PCV7 was rapidly implemented from July 2009. Clinical data
      were collected, pneumococci identified and characterized for antibiotic
      susceptibilities and serotype. Analyses included multivariate logistic models
      with an interaction term for PCV7-effect. RESULTS: Altogether, 2755 children from
      PA (n=1772) and EJ (n=983) were enrolled, of which ~30% were pneumococcal
      carriers. While overall carriage was not affected by vaccination policy, carriage
      of vaccine-type (VT7) strains decreased from 52% to 22% (p<0.001) in EJ, where
      PCV was implemented, but not in PA. This was accompanied by an increase in non
      VT13 strains from 34% to 65% (p<0.001) in EJ, but not in PA. Furthermore, within
      two years post-PCV7 introduction, proportion of multi-drug resistant strains,
      which was initially 23% in both populations, decreased significantly in EJ, to
      10%, while simultaneously it increased in PA to 33% (p<0.001). Similar trends
      were observed for resistance to most antibiotic groups. The proportion of
      resistant isolates among non-VT13 strains did not change during the study period.
      CONCLUSIONS: The unique study design distinguishes secular and seasonal effects
      from true vaccine effects. While PCV7 did not affect overall pneumococcal
      carriage rate, VT7 strains, many of which were antibiotic resistant decreased and
      were replaced by non-VT13 strains, which were mostly not antibiotic resistant,
      resulting in a net decrease in antibiotic resistance.

PMID- 25593105
TI  - 3D digital anatomy modelling - Practical or pretty?
AB  - BACKGROUND: With an increasing move towards digitalisation of medical records and
      medical teaching, such as online exams and webinars, one of the questions that
      persists asks 'is there a place for digital anatomy teaching and can it
      effectively replace the traditional teaching methods such as cadaveric
      dissection?' Cadaveric dissection has a number of benefits as a teaching method
      but it also has its limitations. Although these can be partially addressed by
      prosections and new more "life-like" fixatives, it does not address the lack of
      resources and the increasing pressure to be able to study and learn at home.
      METHODS: This paper reviews the literature with regards to the suitability of
      digital models for teaching and the wider uses a 3D digital anatomy model could
      have, such as postgraduate teaching, patient education and surgical planning. It
      also looks briefly at the learning model that anatomy as art contributes.
      RESULTS: The literature has scattered examples of digital models used for
      teaching at both undergraduate and postgraduate level, which demonstrate a number
      of positive outcomes, mostly surrounding user satisfaction and convenience. 3D
      modelling for patient education and operation planning has less exploration, and
      these papers generate a number of discussion points, mostly surrounding the
      practicality of digital models, which can be more time consuming and require the
      technology to be widely available and reliable. CONCLUSIONS: 3D digital anatomy
      is a useful adjunct to teaching and its use in patient education and operation
      planning have interesting possibilities still to be fully explored.

PMID- 25593107
TI  - Feasibility, acceptability, and effectiveness of visual inspection of the cervix
      with acetic acid and cryotherapy for dysplasia in Nigeria.
AB  - OBJECTIVE: To demonstrate the feasibility, acceptability, and effectiveness of
      visual inspection of the cervix with acetic acid (VIA) and treatment of dysplasia
      with cryotherapy in Nigeria. METHODS: A prospective study was conducted at
      Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria, between August 1,
      2006, and July 31, 2009. Women aged 20-65 years who had had their sexual debut at
      least 3 years previously were screened for cervical dysplasia using VIA. Women
      with positive test results were offered cryotherapy immediately after screening.
      RESULTS: Overall, 5529 women (mean age 40.24 +/- 10.33 years) underwent screening
      with VIA. Dysplasia was detected among 317 (5.7%) women. Lesions suspicious for
      cancer were recorded among 52 (1.0%) women; histological diagnosis of invasive
      cervical cancer was confirmed in 38 (0.7%) women. VIA was as expected or better
      for 5330 (96.4%) women screened. Cryotherapy was as expected or better for 219
      (99.5%) women who received treatment. Among 127 women who underwent cryotherapy
      and had repeat screening, 121 (95.3%) had negative test results after 1 year.
      CONCLUSION: Cervical cancer screening using VIA and cryotherapy was feasible and
      effective despite scarce resources in the Nigerian health system. Furthermore,
      this approach was socially and culturally acceptable.

PMID- 25593106
TI  - Manipulating cell fate in the cochlea: a feasible therapy for hearing loss.
AB  - Mammalian auditory hair cells do not spontaneously regenerate, unlike hair cells
      in lower vertebrates, including fish and birds. In mammals, hearing loss due to
      the loss of hair cells is permanent and intractable. Recent studies in the mouse
      have demonstrated spontaneous hair cell regeneration during a short postnatal
      period, but this regenerative capacity is lost in the adult cochlea. Reduced
      regeneration coincides with a transition that results in a decreased pool of
      progenitor cells in the cochlear sensory epithelium. Here, we review the
      signaling cascades involved in hair cell formation and morphogenesis of the organ
      of Corti in developing mammals, the changing status of progenitor cells in the
      cochlea, and the regeneration of auditory hair cells in adult mammals. 

PMID- 25593108
TI  - An innovative approach to in-service training of maternal health staff in
      Cambodian hospitals.
AB  - OBJECTIVE: To demonstrate the feasibility of implementing evidence-based
      continuing medical education (CME) to improve key skills among maternity staff in
      Cambodia. METHODS: A skills-based CME program was implemented in 33 Cambodian
      hospitals. Each clinical skills practice (CSP) module consisted of a 1-day
      practice session, focusing on three maternal and newborn interventions, followed
      by support visits to participating hospitals. Skills were assessed at 27
      intervention hospitals and five control hospitals 7-11 months after the practice
      sessions through observation of neonatal resuscitation, magnesium sulfate
      dilution, and aortic compression simulations. RESULTS: A total of 559 healthcare
      workers attended at least one CSP practice session. The skills assessment
      included 47 doctors and 210 midwives. Hospital staff who participated in CSP
      performed significantly better than did those from control hospitals on neonatal
      resuscitation (mean score 31.22 vs 17.00; P<0.001), magnesium sulfate dilution
      (mean score 11.01 vs 8.47; P<0.001), and aortic compression (mean score 13.87 vs
      4.33; P<0.001). CSP participants were also significantly more likely to score
      higher than the 70% cutoff for neonatal resuscitation and magnesium sulfate
      dilution than were those from control hospitals, after adjustment for hospital
      level and profession (P<=0.05). CONCLUSION: Key clinical skills in low-resource
      settings can be improved by implementing CME using simulations and supportive
      follow-up.

PMID- 25593110
TI  - The catheter to vein ratio and rates of symptomatic venous thromboembolism in
      patients with a peripherally inserted central catheter (PICC): a prospective
      cohort study.
AB  - BACKGROUND: Peripherally inserted central catheters (PICCs) are a common vascular
      access device used in clinical practice. Their use may be complicated by adverse
      events such as venous thromboembolism (VTE). The size of the vein used for PICC
      insertion and thus the catheter to vein ratio is thought to be a controllable
      factor in the reduction of VTE rates in patients who have a PICC. However, an
      optimal catheter to vein ratio for PICC insertion has not previously been
      investigated to inform clinical practice. OBJECTIVES: To determine the effect of
      the catheter to vein ratio (proportion of the vein measured at the insertion
      point taken up by the catheter) on rates of symptomatic VTE in patients with a
      PICC and identify the optimal ratio cut-off point to reduce rates of this adverse
      event. METHOD: Adult patients waiting for PICC insertion at a large metropolitan
      teaching hospital were recruited between May and December 2013. Vein diameter at
      the PICC insertion site was measured using ultrasound with in-built callipers.
      Participants were followed up at eight weeks to determine if they developed
      symptomatic VTE. RESULTS: Data were available for 136 patients (50% cancer; 44%
      infection; 6% other indication for PICC). Mean age was 57 years with 54% males.
      There were four cases of confirmed symptomatic VTE (two involving the deep veins,
      one peripheral vein and one pulmonary embolism). Receiver operator characteristic
      (ROC) analysis determined that a 45% catheter to vein ratio was the ideal cut off
      point to maximise sensitivity and specificity (AUC 0.761; 95% CI 0.681-0.830).
      When a ratio of 46% or above was compared to one that was less than or equal to
      45% using a log binomial generalised linear model it was found that participants
      with a catheter to vein ratio >45% were 13 times more likely to suffer VTE
      (relative risk 13, p=0.022; CI 1.445-122.788). CONCLUSION: It was found that a
      45% catheter to vein ratio was the optimal cut off with high sensitivity and
      specificity to reduce the risk of VTE. However, further research is needed to
      confirm these results as although adequately powered; the number of cases of VTE
      was comparatively small, resulting in wide confidence intervals.

PMID- 25593109
TI  - Repeat left atrial catheter ablation: cardiac magnetic resonance prediction of
      endocardial voltage and gaps in ablation lesion sets.
AB  - BACKGROUND: Studies have reported an inverse relationship between late gadolinium
      enhancement (LGE) cardiac magnetic resonance (CMR) signal intensity and left
      atrial (LA) endocardial voltage after LA ablation. However, there is controversy
      regarding the reproducibility of atrial LGE CMR and its ability to identify gaps
      in ablation lesions. Using systematic and objective techniques, this study
      examines the correlation between atrial CMR and endocardial voltage. METHODS AND
      RESULTS: Twenty patients who had previous ablation for atrial fibrillation and
      represented with paroxysmal atrial fibrillation or atrial tachycardia underwent
      preablation LGE CMR. During the ablation procedure, high-density point-by-point
      Carto voltage maps were acquired. Three-dimensional CMR reconstructions were
      registered with the Carto anatomies to allow comparison of voltage and LGE signal
      intensity. Signal intensities around the left and right pulmonary vein antra and
      along the LA roof and mitral lines on the CMR-segmented LA shells were extracted
      to examine differences between electrically isolated and reconnected lesions.
      There were a total of 6767 data points across the 20 patients. Only 119 (1.8%) of
      the points were <= 0.05 mV. There was only a weak inverse correlation between
      either unipolar (r = -0.18) or bipolar (r = -0.17) voltage and LGE CMR signal
      intensities with low voltage occurring across a large range of signal
      intensities. Signal intensities were not statistically different for electrically
      isolated and reconnected lesions. CONCLUSIONS: This study demonstrates that there
      is only a weak point-by-point relationship between LGE CMR and endocardial
      voltage in patients undergoing repeat LA ablation. Using an objective method of
      assessing gaps in ablation lesions, LGE CMR is unable to reliably predict sites
      of electrical conduction.

PMID- 25593111
TI  - Antioxidant intake and bone status in a cross-sectional study of Brazilian women
      with osteoporosis.
AB  - This study aimed to investigate the association between antioxidant intake and
      bone mineral density (BMD) in postmenopausal women with osteoporosis. We
      conducted a cross-sectional study with 150 women, mean age 68.7 (SD 9.1) years.
      BMD and body composition were obtained using dual-energy X-ray absorptiometry
      (DXA). We assessed anthropometric measures and dietary intake and applied an
      adapted Dietary Antioxidant Quality Score (a-DAQS) to evaluate the antioxidant
      consumption. 65.3% of women had higher scores on the a-DAQS. We found no
      relationship between the a-DAQS and BMD; however, we observed an inverse
      correlation between vitamin A and lumbar spine (LS) BMD in g/cm(2) (r = - 0.201;
      p = 0.013). An analysis of variance (ANOVA) test also showed that vitamin A was
      negatively associated with the LS BMD (F = 6.143; p = 0.013, but without
      significance when a multivariate analysis was applied. The a-DAQS did not have an
      association with BMD; however, Vitamin A showed a negative correlation with BMD,
      but such an association disappeared when the other antioxidants were taken
      together. Our findings encourage an antioxidant-based dietary approach to
      osteoporosis prevention and treatment, since the negative effect of vitamin A was
      neutralized by the intake of such nutrients. 

PMID- 25593112
TI  - Use of 11C-PE2I PET in differential diagnosis of parkinsonian disorders.
AB  - In idiopathic Parkinson disease and atypical parkinsonian disorders, central
      dopaminergic and overall brain functional activity are altered to different
      degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A
      dual examination using (123)I-FP-CIT ((123)I-N-omega-fluoropropyl-2beta
      carbomethoxy-3beta-(4-iodophenyl)nortropane, or (123)I-ioflupane) SPECT and(18)F
      FDG PET provides complementary information on dopamine transporter (DAT)
      availability and overall brain functional activity, respectively. Parametric
      images based on a single, dynamic (11)C-PE2I (N-(3-iodoprop-2E-enyl)-2beta
      carbomethoxy-3beta-(4-methyl-phenyl)nortropane) scan potentially supply both DAT
      availability (nondisplaceable binding potential [BPND]) and relative cerebral
      blood flow (relative delivery [R1]) at voxel level. This study aimed to evaluate
      the validity of (11)C-PE2I PET against the dual-modality approach using (123)I-FP
      CIT SPECT and (18)F-FDG PET. METHODS: Sixteen patients with parkinsonian
      disorders had a dual examination with (18)F-FDG PET and (123)I-FP-CIT SPECT
      following clinical routines and additionally an experimental (11)C-PE2I PET scan.
      Parametric BPND and R1 images were generated using receptor parametric mapping
      with the cerebellum as a reference. T1-weighted MR imaging was used for automated
      definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia,
      whereas the overall brain functional activity was examined using VOIs across the
      brain. BPND and R1 values were compared with normalized (123)I-FP-CIT and (18)F
      FDG uptake values, respectively, using Pearson correlations and regression
      analyses. In addition, 2 masked interpreters evaluated the images visually, in
      both the routine and the experimental datasets, for comparison of patient
      diagnoses. RESULTS: Parametric (11)C-PE2I BPND and R1 images showed high
      consistency with (123)I-FP-CIT SPECT and (18)F-FDG PET images. Correlations
      between (11)C-PE2I BPND and (123)I-FP-CIT uptake ratios were 0.97 and 0.76 in the
      putamen and caudate nucleus, respectively. Regional (11)C-PE2I R1 values were
      moderately to highly correlated with normalized (18)F-FDG values (range, 0.61
      0.94). Visual assessment of DAT availability showed a high consistency between
      (11)C-PE2I BPND and (123)I-FP-CIT images, whereas the consistency was somewhat
      lower for appraisal of overall brain functional activity using (123)I-FP-CIT and
      (18)F-FDG images. Substantial differences were found between clinical diagnosis
      and both neuroimaging diagnoses. CONCLUSION: A single, dynamic (11)C-PE2I PET
      investigation is a powerful alternative to a dual examination with (123)I-FP-CIT
      SPECT and (18)F-FDG PET for differential diagnosis of parkinsonian disorders. A
      large-scale patient study is, however, needed to further investigate distinct
      pathologic patterns in overall brain functional activity for various parkinsonian
      disorders.

PMID- 25593113
TI  - 18F-fluoride PET used for treatment monitoring of systemic cancer therapy:
      results from the National Oncologic PET Registry.
AB  - In a national prospective registry, we previously studied the impact of (18)F
      sodium fluoride PET (NaF PET) on the intended management of cancer patients with
      osseous metastases. The clinical impact of NaF PET for monitoring the response to
      systemic therapies in such patients is unknown. The objective of this study was
      to assess the impact of NaF PET results obtained for treatment monitoring of
      systemic cancer therapy. METHODS: Before and after NaF PET, we collected
      prospective data from referring and interpreting physicians for cancer patients
      65 y or older receiving systemic therapy (use of 1 or more categories including
      hormonal, chemotherapy, bisphosphonates, or immunotherapy). The analysis set
      consisted of 2,217 patients who underwent 2,839 scans (68% prostate, 17% breast,
      6% lung, and 8% other cancers) ordered for treatment monitoring. Two or more
      categories of systemic therapy were planned in 56% of prostate and 43% of breast
      cancer patients. RESULTS: The overall rates of prior radionuclide bone imaging
      were 78%, 76%, and 66% for prostate, breast, and other cancers, respectively.
      Fifty-seven percent of patients underwent prior NaF PET. Overall change in
      management associated with NaF PET was 40%. In patients with prior NaF PET scans
      for comparison, continuing current therapy was planned in 79% when scans showed
      no change or a decrease or absence of osseous metastasis. Treating physicians
      planned to switch therapy in 59% of patients after scans showed evidence of new
      or progressive metastasis. When an additional parameter, estimated prognosis, was
      worse, switching therapy was even more common (76%). CONCLUSION: The impact of
      NaF PET used for treatment monitoring was high in patients with evidence of
      progressive osseous metastasis. Most such patients had plans to switch to a new
      cancer-directed therapy.

PMID- 25593114
TI  - Combined PET/MR: a technology becomes mature.
AB  - The combination of PET and MR imaging forms a powerful new imaging modality,
      PET/MR. The major advantages of concurrent PET/MR acquisitions range from patient
      comfort and increased throughput to multiparametric imaging and are evaluated and
      reviewed in this paper specifically with respect to their applications in
      research and diagnostics. Alongside the use of PET/MR in the field of preclinical
      research, this paper illuminates the impact of this new modality in the clinical
      field in such areas as neurology, oncology, and cardiology. Now that PET/MR
      technology has matured, attention is needed on standardizing education for
      nuclear and radiologic technologists and physicians specifically for this
      combined modality. Furthermore, the impact of this combined modality on health
      economy needs to be addressed in more detail to further propel its use. 

PMID- 25593115
TI  - Dose response of pancreatic neuroendocrine tumors treated with peptide receptor
      radionuclide therapy using 177Lu-DOTATATE.
AB  - Peptide receptor radionuclide therapy (PRRT) is a promising treatment for
      patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric
      calculations in relation to PRRT have been concentrated to normal organ dosimetry
      in order to limit side effects. However, the relation between the absorbed dose
      to the tumor and treatment response has so far not been established. Better
      knowledge in this respect may improve the understanding of treatment effects,
      allow for improved selection of those patients who are expected to benefit from
      PRRT, and avoid unnecessary treatments. The aim of the present work was to
      evaluate the dose-response relationship for pancreatic neuroendocrine tumors
      treated with PRRT using (177)Lu-DOTATATE. METHODS: Tumor-absorbed dose
      calculations were performed for 24 lesions in 24 patients with metastasized
      pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE
      at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT
      imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density
      sphere model from OLINDA was used for absorbed dose calculations. The absorbed
      doses were corrected for partial-volume effect based on phantom measurements. On
      the basis of these results, only tumors larger than 2.2 cm in diameter at any
      time during the treatment were included for analysis. To further decrease the
      effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed
      separately. Tumor response was evaluated by CT using Response Evaluation Criteria
      In Solid Tumors. RESULTS: Tumor-absorbed doses until best response ranged
      approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the
      data, and a significant correlation between the absorbed dose and tumor reduction
      was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors
      larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The
      largest tumor reduction was 57% after a total absorbed dose of 170 Gy.
      CONCLUSION: The results imply a significant correlation between absorbed dose and
      tumor reduction. However, further studies are necessary to address the large
      variations in response for similar absorbed doses.

PMID- 25593116
TI  - Somatostatin receptor-targeted radiopeptide therapy with 90Y-DOTATOC and 177Lu
      DOTATOC in progressive meningioma: long-term results of a phase II clinical
      trial.
AB  - Meningiomas express members of the somatostatin receptor family. The present
      study assessed the long-term benefits and harm of somatostatin-based radiopeptide
      therapy in meningioma patients. METHODS: Patients with progressive unresectable
      meningioma were treated with (90)Y-DOTATOC and (177)Lu-DOTATOC until tumor
      progression or permanent toxicity occurred. Multivariable Cox regression analyses
      were used to study predictors of survival. RESULTS: Overall, 74 treatment cycles
      were performed on 34 patients. Stable disease was achieved in 23 patients. Severe
      hematotoxicity occurred in 3 patients, and severe renal toxicity in 1 patient.
      Mean survival was 8.6 y from the time of recruitment. Stable disease after
      treatment (hazard ratio, 0.017 vs. progressive disease; 95% confidence interval,
      0.001-0.35; n = 34; P = 0.01) and high tumor uptake (hazard ratio, 0.046 vs.
      intermediate or low tumor uptake; 95% confidence interval, 0.004-0.63; n = 34; P
      = 0.019) were associated with longer survival. CONCLUSION: (90)Y-DOTATOC and
      (177)Lu-DOTATOC are promising tools for treating progressive unresectable
      meningioma, especially in cases of high tracer uptake in the tumor.

PMID- 25593117
TI  - 123I-iododexetimide preferentially binds to the muscarinic receptor subtype M1 in
      vivo.
AB  - The muscarinic M1 receptor (M1R) is highly involved in cognition, and selective
      M1 agonists have procognitive properties. Loss of M1R has been found in
      postmortem brain tissue for several neuropsychiatric disorders and may be related
      to symptoms of cognitive dysfunction. (123)I-iododexetimide is used for imaging
      muscarinic acetylcholine receptors (mAchRs). Considering its high brain uptake
      and intense binding in M1R-rich brain areas, (123)I-iododexetimide may be an
      attractive radiopharmaceutical to image M1R. To date, the binding affinity and
      selectivity of (123)I-iododexetimide for the mAchR subtypes has not been
      characterized, nor has its brain distribution been studied intensively.
      Therefore, this study aimed to address these topics. METHODS: The in vitro
      affinity and selectivity of (127)I-iododexetimide (cold-labeled iododexetimide),
      as well as its functional antagonist properties (guanosine 5'-[gamma-(35)S
      thio]triphosphate [GTPgamma(35)S] assay), were assessed on recombinant human M1R
      M5R. Distributions of (127)I-iododexetimide and (123)I-iododexetimide in the
      brain were evaluated using liquid chromatography-mass spectrometry and storage
      phosphor imaging, respectively, ex vivo in rats, wild-type mice, and M1-M5 knock
      out (KO) mice. Inhibition of (127)I-iododexetimide and (123)I-iododexetimide
      binding in M1R-rich brain areas by the M1R/M4R agonist xanomeline, or the
      antipsychotics olanzapine (M1R antagonist) and haloperidol (low M1R affinity),
      was assessed in rats ex vivo. RESULTS: In vitro, (127)I-iododexetimide displayed
      high affinity for M1R (pM range), with modest selectivity over other mAchRs. In
      biodistribution studies on rats, ex vivo (127)I-iododexetimide binding was much
      higher in M1R-rich brain areas, such as the cortex and striatum, than in
      cerebellum (devoid of M1Rs). In M1 KO mice, but not M2-M5 KO mice, (127)I
      iododexetimide binding was strongly reduced in the frontal cortex compared with
      wild-type mice. Finally, acute administration of both an M1R/M4R agonist
      xanomeline and the M1R antagonist olanzapine was able to inhibit (123)I
      iododexetimide ex vivo, and (123)I-iododexetimide binding in M1-rich brain areas
      in rats, whereas administration of haloperidol had no effect. CONCLUSION: The
      current results suggest that (123)I-iododexetimide preferentially binds to M1R in
      vivo and can be displaced by M1R ligands. (123)I-iododexetimide may therefore be
      a useful imaging tool as a way to further evaluate M1R changes in
      neuropsychiatric disorders, as a potential stratifying biomarker, or as a
      clinical target engagement biomarker to assess M1R.

PMID- 25593118
TI  - 18F-FDG or 3'-deoxy-3'-18F-fluorothymidine to detect transformation of follicular
      lymphoma.
AB  - Considering the different treatment strategy for transformed follicular lymphoma
      (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in
      the disease course is important. There is evidence that (18)F-FDG has utility as
      a biomarker of transformation. However, quantitative thresholds may require
      inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences
      in tracer uptake per subtype. Moreover, because proliferation is a hallmark of
      transformation, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) might be superior
      to (18)F-FDG in this setting. To define the best tracer for detection of TF, we
      performed a prospective a head-to-head comparison of (18)F-FDG and (18)F-FLT in
      patients with FL and TF. METHODS: (18)F-FDG and (18)F-FLT PET scans were obtained
      in 17 patients with FL and 9 patients with TF. We measured the highest maximum
      standardized uptake value (SUVmax), defined as the lymph node with the highest
      uptake per patient, and SUVrange, defined as the difference between the SUVmax of
      the lymph node with the highest and lowest uptake per patient. To reduce partial
      volume effects, only lymph nodes larger than 3 cm(3) (A50 isocontour) were
      analyzed. Scans were acquired 1 h after injection of 185 MBq of (18)F-FDG or
      (18)F-FLT. To determine the discriminative ability of SUVmax and SUVrange of both
      tracers for TF, receiver-operating-characteristic curve analysis was performed.
      RESULTS: The highest SUVmax was significantly higher for TF than FL for both
      (18)F-FDG and (18)F-FLT (P < 0.001). SUVrange was significantly higher for TF
      than FL for (18)F-FDG (P = 0.029) but not for (18)F-FLT (P = 0.075). The ability
      of (18)F-FDG to discriminate between FL and TF was superior to that of (18)F-FLT
      for both the highest SUVmax (P = 0.039) and the SUVrange (P = 0.012). The cutoff
      value for the highest SUVmax of (18)F-FDG aiming at 100% sensitivity with a
      maximum specificity was found to be 14.5 (corresponding specificity, 82%). For
      (18)F-FLT, these values were 5.1 and 18%, respectively. When the same method was
      applied to SUVrange, the cutoff values were 5.8 for (18)F-FDG (specificity, 71%)
      and 1.5 for (18)F-FLT (specificity, 36%). CONCLUSION: Our data suggest that (18)F
      FDG PET is a better biomarker for TF than (18)F-FLT PET. The proposed thresholds
      of highest SUVmax and SUVrange should be prospectively validated.

PMID- 25593119
TI  - Test-retest reproducibility of binding parameters in humans with 11C-LY2795050,
      an antagonist PET radiotracer for the kappa opioid receptor.
AB  - (11)C-LY2795050 is a new antagonist PET radioligand for the kappa opioid receptor
      (KOR). In this study, we assessed the reproducibility of the binding parameters
      of (11)C-LY2795050 in healthy human subjects. METHODS: Sixteen healthy subjects
      (11 men and 5 women) underwent 2 separate 90-min PET scans with arterial input
      function and plasma free fraction (fP) measurements. The 2-tissue-compartment
      model and multilinear analysis-1 were applied to calculate 5 outcome measures in
      14 brain regions: distribution volume (VT), VT normalized by fP (VT/fP), and 3
      binding potentials (nondisplaceable binding potential, binding potential relative
      to total plasma concentration, and binding potential relative to free plasma
      concentration: BPND, BPP, BPF, respectively). Since KOR is distributed
      ubiquitously throughout the brain, there are no suitable reference regions. We
      used a fixed fraction of individual cerebellar VT value (VT,CER) as the
      nondisplaceable VT (VND) (VND = VT,CER/1.17). The relative and absolute test
      retest variability and intraclass correlation coefficient were evaluated for the
      outcome measures of (11)C-LY2795050. RESULTS: The test-retest variability of
      (11)C-LY2795050 for VT was no more than 10% in any region and was 12% in the
      amygdala. For binding potential (BPND and BPP), the test-retest variability was
      good in regions of moderate and high KOR density (BPND > 0.4) and poor in regions
      of low density. Correction by fP (VT/fP or BPF) did not improve the test-retest
      performance. CONCLUSION: Our results suggest that quantification of (11)C
      LY2795050 imaging is reproducible and reliable in regions with moderate and high
      KOR density. Therefore, we conclude that this first antagonist radiotracer is
      highly useful for PET studies of KOR.

PMID- 25593120
TI  - Evaluation of renal function before and after percutaneous mitral valve repair.
AB  - BACKGROUND: Chronic kidney disease (CKD) is strongly related to outcome in
      cardiovascular diseases. The relationship between treatment of mitral
      regurgitation (MR) and renal function is not well described. We sought to
      evaluate renal function before and after mitral valve repair by the MitraClip
      device. METHODS AND RESULTS: Patients with moderate-to-severe or severe (3+ or
      4+, respectively) MR by core laboratory determination who underwent transcatheter
      mitral valve repair with the MitraClip device in multicenter, investigational
      trials were included in this study. Estimated glomerular filtration rate (eGFR)
      was evaluated before and at hospital discharge, 30 days, 6 months, and 1 year
      after mitral valve repair. Eight hundred fifty-four patients with baseline mean
      eGFR 61.5 +/- 23.1 mL/min/1.73 m(2) were studied, including 438 (51.3%) with eGFR
      >= 60 mL/min/1.73 m(2) (CKD stage 1 or 2), 371 (42.6%) with eGFR 30 to 59
      mL/min/1.73 m(2) (CKD stage 3), and 52 (6.1%) with eGFR < 30 mL/min/1.73 m(2)
      (CKD stage 4 or 5). Baseline renal dysfunction was more prevalent in older
      patients with a history of heart failure, coronary artery disease,
      cerebrovascular disease, diabetes mellitus, hypertension, and atrial
      fibrillation. Baseline eGFR was associated with 1-year survival (P < 0.001) after
      MitraClip repair. At 1-year follow-up, the mean change in eGFR for the overall
      cohort was -1.0 +/- 15.1 mL/min/1.73 m(2); for patients with CKD stage 1 or 2,
      stage 3, or stage 4 or 5, mean change was -4.1 +/- 16.6, +2.6 +/- 12.4, and +4.8
      +/- 9.5 mL/min/1.73 m(2), respectively. Linear mixed effect modeling demonstrated
      a strong association between MR and eGFR, and a statistically significant
      improvement in eGFR in patients with CKD stage 4 or 5 associated with MR
      reduction to <= 2+ (P = 0.007). CONCLUSIONS: Renal dysfunction is associated with
      lower survival in patients with severe MR even after percutaneous mitral valve
      repair. Reduction in MR severity by the MitraClip device is associated with
      improvement in renal function at 1 year in patients with baseline renal
      dysfunction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifiers: NCT00209274, NCT01931956, NCT01940120.

PMID- 25593121
TI  - Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute
      iliofemoral deep vein thrombosis.
AB  - BACKGROUND: For patients with acute iliofemoral deep vein thrombosis, it remains
      unclear whether the addition of intravascular high-frequency, low-power
      ultrasound energy facilitates the resolution of thrombosis during catheter
      directed thrombolysis. METHODS AND RESULTS: In a controlled clinical trial, 48
      patients (mean age 50 +/- 21 years, 52% women) with acute iliofemoral deep vein
      thrombosis were randomized to receive ultrasound-assisted catheter-directed
      thrombolysis (N = 24) or conventional catheter-directed thrombolysis (N = 24).
      Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients.
      The primary efficacy end point was the percentage of thrombus load reduction from
      baseline to 15 hours according to the length-adjusted thrombus score, obtained
      from standardized venograms and evaluated by a core laboratory blinded to group
      assignment. The percentage of thrombus load reduction was 55% +/- 27% in the
      ultrasound-assisted catheter-directed thrombolysis group and 54% +/- 27% in the
      conventional catheter-directed thrombolysis group (P = 0.91). Adjunctive
      angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%)
      patients, respectively (P > 0.99). Treatment-related complications occurred in 3
      (12%) and 2 (8%) patients, respectively (P > 0.99). At 3-month follow-up, primary
      venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis
      group and 96% in the conventional catheter-directed thrombolysis group (P =
      0.33), and there was no difference in the severity of the post-thrombotic
      syndrome (mean Villalta score: 3.0 +/- 3.9 [range 0-15] versus 1.9 +/- 1.9 [range
      0-7]; P=0.21), respectively. CONCLUSIONS: In this randomized controlled clinical
      trial of patients with acute iliofemoral deep vein thrombosis treated with a
      fixed-dose catheter thrombolysis regimen, the addition of intravascular
      ultrasound did not facilitate thrombus resolution. CLINICAL TRIAL REGISTRATION
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT01482273.

PMID- 25593122
TI  - Coronary obstruction in transcatheter aortic valve-in-valve implantation:
      preprocedural evaluation, device selection, protection, and treatment.

PMID- 25593123
TI  - The search for exercise factors in humans.
AB  - Regular exercise reduces the risk for numerous chronic diseases. Exercise not
      only impacts the contracting skeletal muscle but also elicits systemic changes.
      The exact mechanisms driving the more systemic changes have yet to be resolved,
      but exercise factors are thought to be an important missing link. Exercise
      factors are proteins that are released from skeletal muscle into the circulation
      during exercise. They represent a subclass of myokines, which are classified as
      proteins secreted from skeletal muscle serving a signaling role. Here, we provide
      an overview of the current literature on myokines. Many studies have focused on
      the identification of new myokines using a variety of approaches. These studies
      have generated an extensive list of myokines, but so far, the functional
      relevance of many of these novel myokines remains unclear. Few of these myokines
      represent putative exercise factors. Currently, IL-6, secreted protein acidic and
      rich in cysteine, angiopoietin-like 4, chemokine (C-X3-C motif) ligand 1, and
      chemokine (C-C motif) ligand 2 have the highest potential to serve as exercise
      factors because for all these factors, there is clear evidence that plasma levels
      increase during exercise. In our view, the future focus should be on
      characterizing the functional role of myokines in the acute and chronic response
      to exercise and explore their potential as a target for metabolic diseases.

PMID- 25593126
TI  - Left atrial remodeling and function in advanced heart failure with preserved or
      reduced ejection fraction.
AB  - BACKGROUND: Left atrial (LA) structure and function are altered in most heart
      failure (HF) patients, but there may be fundamental differences in LA properties
      between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS
      AND RESULTS: One hundred ninety-eight HF patients (51% HFpEF, New York Heart
      Association 3.1+/-0.7) and 40 HF-free controls underwent catheterization,
      echocardiography, and follow-up. Compared with controls, HF patients had larger
      and more dysfunctional left atria. At identical mean LA pressure (20 versus 20 mm
      Hg; P=0.9), HFrEF patients had larger LA volumes (LA volume index 50 versus 41
      mL/m(2); P<0.001), whereas HFpEF patients had higher LA peak pressures, lower LA
      minimal pressures, higher LA stiffness (0.79 versus 0.48 mm Hg/mL; P<0.001),
      greater LA pulsatility (19 versus 13 mm Hg; P<0.001), and higher wall stress
      variations. Despite smaller LA volumes, better function, and less mitral
      regurgitation, HFpEF patients had more atrial fibrillation (42 versus 26%;
      P=0.02). LA dysfunction was associated with increased pulmonary vascular
      resistance and right ventricular dysfunction in both HF phenotypes. After a
      median follow-up of 350 days, 31 HFpEF and 28 HFrEF patients died. LA function
      (total LA EF) was associated with lower mortality in HFpEF (hazard ratio 0.43;
      95% confidence interval, 0.2-0.9; P<0.05), but not in HFrEF. CONCLUSIONS: HFrEF
      is characterized by greater eccentric LA remodeling, whereas HFpEF by increased
      LA stiffness, which might contribute to greater atrial fibrillation burden. LA
      function is associated with pulmonary vascular disease and right HF in both HF
      phenotypes, but is associated with outcome more closely in HFpEF, supporting
      efforts to improve LA function in this cohort.

PMID- 25593125
TI  - Different mechanisms of apolipoprotein E isoform-dependent modulation of
      prostaglandin E2 production and triggering receptor expressed on myeloid cells 2
      (TREM2) expression after innate immune activation of microglia.
AB  - Several lines of evidence support immune response in brain as a mechanism of
      injury in Alzheimer disease (AD). Moreover, immune activation is heightened in
      apolipoprotein E (APOE) epsilon4 carriers; inhibitors of prostaglandin (PG)
      synthesis show a partially protective effect on AD risk from APOE epsilon4; and
      genetic variants in triggering receptor expressed on myeloid cells 2 (TREM2) are
      a rare but potent risk for AD. We tested the hypothesis that APOE epsilon4
      inheritance modulates both the PGE2 pathway and TREM2 expression using primary
      murine microglia from targeted replacement (TR) APOE3/3 and APOE4/4 mice.
      Microglial cyclooxygenase-2, microsomal PGE synthase, and PGE2 expression were
      increased 2- to 25-fold in both genotypes by TLR activators; however, this
      induction was significantly (P < 0.01) greater in TR APOE4/4 microglia with TLR3
      and TLR4 activators. Microglial TREM2 expression was reduced approximately 85% by
      all TLR activators; this reduction was approximately one-third greater in
      microglia from TR APOE4/4 mice. Importantly, both receptor-associated protein and
      a nuclear factor kappa-light-chain-enhancer inhibitor blocked TR APOE4/4
      dependent effects on the PGE2 pathway but not on TREM2 expression. These data
      demonstrate complementary, but mechanistically distinct, regulation of pro- and
      anti-inflammatory mediators in TR APOE4/4 murine microglia that yields a more
      proinflammatory state than with TR APOE3/3.

PMID- 25593124
TI  - SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion.
AB  - Genes that regulate osteoclast (OC) development and function in both physiologic
      and disease conditions remain incompletely understood. Shp2 (the Src homology-2
      domain containing protein tyrosine phosphatase 2), a ubiquitously expressed
      cytoplasmic protein tyrosine phosphatase, is implicated in regulating M-CSF and
      receptor activator of nuclear factor-kappaB ligand (RANKL)-evoked signaling; its
      role in osteoclastogenesis and bone homeostasis, however, remains unknown. Using
      a tissue-specific gene knockout approach, we inactivated Shp2 expression in
      murine OCs. Shp2 mutant mice are phenotypically osteopetrotic, featuring a marked
      increase of bone volume (BV)/total volume (TV) (+42.8%), trabeculae number (Tb.N)
      (+84.1%), structure model index (+119%), and a decrease of trabecular thickness
      (Tb.Th) (-34.1%) and trabecular spacing (Tb.Sp) (-41.0%). Biochemical analyses
      demonstrate that Shp2 is required for RANKL-induced formation of giant
      multinucleated OCs by up-regulating the expression of nuclear factor of activated
      T cells, cytoplasmic 1 (Nfatc1), a master transcription factor that is
      indispensable for terminal OC differentiation. Shp2 deletion, however, has
      minimal effect on M-CSF-dependent survival and proliferation of OC precursors.
      Instead, its deficiency aborts the fusion of OC precursors and formation of
      multinucleated OCs and decreases bone matrix resorption. Moreover,
      pharmacological intervention of Shp2 is sufficient to prevent preosteoclast
      fusion in vitro. These findings uncover a novel mechanism through which Shp2
      regulates osteoclastogenesis by promoting preosteoclast fusion. Shp2 or its
      signaling partners could potentially serve as pharmacological targets to regulate
      the population of OCs locally and/or systematically, and thus treat OC-related
      diseases, such as periprosthetic osteolysis and osteoporosis.

PMID- 25593128
TI  - N-cadherin negatively regulates collective Drosophila glial migration through
      actin cytoskeleton remodeling.
AB  - Cell migration is an essential and highly regulated process. During development,
      glia cells and neurons migrate over long distances - in most cases collectively -
      to reach their final destination and build the sophisticated architecture of the
      nervous system, the most complex tissue of the body. Collective migration is
      highly stereotyped and efficient, defects in the process leading to severe human
      diseases that include mental retardation. This dynamic process entails extensive
      cell communication and coordination, hence, the real challenge is to analyze it
      in the entire organism and at cellular resolution. We here investigate the impact
      of the N-cadherin adhesion molecule on collective glial migration, by using the
      Drosophila developing wing and cell-type specific manipulation of gene
      expression. We show that N-cadherin timely accumulates in glial cells and that
      its levels affect migration efficiency. N-cadherin works as a molecular brake in
      a dosage-dependent manner, by negatively controlling actin nucleation and
      cytoskeleton remodeling through alpha/beta catenins. This is the first in vivo
      evidence for N-cadherin negatively and cell autonomously controlling collective
      migration. 

PMID- 25593127
TI  - Basolateral secretion of Wnt5a in polarized epithelial cells is required for
      apical lumen formation.
AB  - Wnt5a regulates planar cell polarity in epithelial cells, but it remains to be
      determined whether Wnt5a and its receptors are sorted apically or basolaterally,
      and how Wnt5a signaling is involved in apical and basolateral polarization. We
      found that Wnt5a was secreted basolaterally in polarized kidney epithelial cells.
      The basolateral secretion of Wnt5a required Wntless (Wls), clathrin and adaptor
      protein 1 (AP-1). Wnt5a receptors were also localized to the basolateral
      membranes, but their sorting did not require Wls. Wnt5a-induced signaling was
      stimulated more efficiently at the basolateral side than the apical side of
      epithelial cells. Knockdown of Wnt5a delayed apical lumen formation of the
      epithelial cyst, and these phenotypes were rescued by wild-type Wnt5a, but not by
      a Wnt5a mutant that is secreted apically. Although apoptosis was not required for
      apical lumen formation in a wild-type cyst, apoptosis was necessary for
      eliminating luminal cells in a Wnt5a-depleted cyst. These results suggest that
      Wnt5a and its receptors are sorted to their correct destination by different
      mechanisms and that the basolateral secretion of Wnt5a is necessary for apical
      lumen formation in the epithelial cyst. 

PMID- 25593129
TI  - The nuclear receptor FXR uncouples the actions of miR-33 from SREBP-2.
AB  - OBJECTIVE: To determine whether activation of farnesoid X receptor (FXR) alters
      cellular and plasma cholesterol homeostasis as a result of regulation of Srebp-2
      and miR-33. APPROACH AND RESULTS: Chromatin immunoprecipitation sequencing data
      identified an FXR response element within intron 10 of the Srebp-2 gene.
      Consistent with this observation, treatment of mice with FXR-specific agonists
      (GSK2324 or GW4064) rapidly increased hepatic levels of Srebp-2 mRNA, precursor
      sterol response element binding protein 2 (pSREBP-2) protein, and miR-33.
      Furthermore, miR-33 targets, that include ABCA1 (ATP binding cassette transporter
      A1), NSF (N-ethylmaleimide-sensitive factor), and CPT1 (carnitine
      palmitoyltransferase 1), were all reduced in GSK2324-treated mice. In contrast,
      neither nuclear SREBP-2 protein (nSREBP-2) nor SREBP-2 target genes were induced
      after FXR activation. The inability to process pSREBP-2 to nSREBP-2 is likely a
      consequence of the induction of insulin INSIG-2A (induced gene 2A) by FXR
      agonists. Finally, we show that FXR-dependent induction of both Srebp-2 and miR
      33 is ablated in Scap(-/-) mice that lack nuclear SREBP-2. CONCLUSIONS: We
      demonstrate that the activation of FXR uncouples the expression of nuclear SREBP
      2 and miR-33, and the regulation of their respective target genes. Further, we
      conclude that the FXR agonist-dependent increase in miR-33 requires transcription
      of the Srebp-2 gene.

PMID- 25593130
TI  - Circulating total bilirubin and risk of incident cardiovascular disease in the
      general population.
AB  - OBJECTIVE: To assess the association of circulating total bilirubin and
      cardiovascular disease (CVD) risk in a new prospective study and to determine
      whether adding information on total bilirubin values to established
      cardiovascular risk factors is associated with improvement in prediction of CVD
      risk. APPROACH AND RESULTS: Circulating total bilirubin levels were measured at
      baseline in the PREVEND (Prevention of Renal and Vascular End-stage Disease)
      prospective study of 7222 participants and 773 incident CVD events. Total
      bilirubin was log-linearly associated with CVD risk. Age- and sex-adjusted hazard
      ratio (95% confidence interval) for CVD per 1-SD increase in loge total bilirubin
      was 0.82 (0.76 to 0.88; P<0.001), which was minimally attenuated to 0.89 (0.82 to
      0.96; P=0.003) after further adjustment for established risk factors. In a meta
      analysis of 12 population-based prospective studies involving 9378 incident CVD
      cases, the pooled multivariate-adjusted relative risk (95% confidence interval)
      for CVD was 0.93 (0.90 to 0.97; P<0.001) per 1-SD increase in total bilirubin
      levels. The corresponding pooled risks for coronary heart disease and stroke were
      0.95 (0.92 to 0.99; P=0.018) and 0.93 (0.88 to 0.98; P=0.006), respectively.
      Addition of information on total bilirubin to a CVD risk prediction model
      containing established risk factors was associated with a C-index change of
      0.0013 (-0.0004 to 0.0029; P=0.13). CONCLUSIONS: There is a log-linear inverse
      association between circulating total bilirubin level and CVD risk, which is
      independent of established risk factors. Nonetheless, inclusion of total
      bilirubin in the standard established risk factors panel provides no significant
      improvement in CVD risk prediction.

PMID- 25593131
TI  - Characterization of a novel function-blocking antibody targeted against the
      platelet P2Y1 receptor.
AB  - OBJECTIVE: Platelet hyperactivity is associated with vascular disease and
      contributes to the genesis of thrombotic disorders. ADP plays an important role
      in platelet activation and activates platelets through 2 G-protein-coupled
      receptors, the Gq-coupled P2Y1 receptor (P2Y1R), and the Gi-coupled P2Y12
      receptor. Although the involvement of the P2Y1R in thrombogenesis is well
      established, there are no antagonists that are currently available for clinical
      use. APPROACH AND RESULTS: Our goal is to determine whether a novel antibody
      targeting the ligand-binding domain, ie, second extracellular loop (EL2) of the
      P2Y1R (EL2Ab) could inhibit platelet function and protect against thrombogenesis.
      Our results revealed that the EL2Ab does indeed inhibit ADP-induced platelet
      aggregation, in a dose-dependent manner. Furthermore, EL2Ab was found to inhibit
      integrin GPIIb-IIIa activation, dense and alpha granule secretion, and
      phosphatidylserine exposure. These inhibitory effects translated into protection
      against thrombus formation, as evident by a prolonged time for occlusion in a
      FeCl3-induced thrombosis model, but this was accompanied by a prolonged tail
      bleeding time. We also observed a dose-dependent displacement of the radiolabeled
      P2Y1R antagonist [(3)H]MRS2500 from its ligand-binding site by EL2Ab.
      CONCLUSIONS: Collectively, our findings demonstrate that EL2Ab binds to and
      exhibits P2Y1R-dependent function-blocking activity in the context of platelets.
      These results add further evidence for a role of the P2Y1R in thrombosis and
      validate the concept that targeting it is a relevant alternative or complement to
      current antiplatelet strategies.

PMID- 25593133
TI  - Maternal high-fat diet exaggerates atherosclerosis in adult offspring by
      augmenting periaortic adipose tissue-specific proinflammatory response.
AB  - OBJECTIVE: Maternal obesity elicits offspring's metabolic disorders via
      developmental modifications of visceral adipose tissue; however, its effect on
      atherogenesis remains undefined. Perivascular adipose tissue has recently been
      implicated in vascular remodeling and vasoreactivity. We hypothesize that
      developmental modifications of perivascular adipose tissue by maternal high-fat
      diet (HFD) exposure promotes atherosclerosis in adult offspring. APPROACH AND
      RESULTS: Eight-week-old female apolipoprotein E-deficient mice were fed an HFD or
      normal diet (ND) during gestation and lactation. Offspring were fed a high
      cholesterol diet from 8 weeks of age. Twenty-week-old male offspring of HFD-fed
      dams (O-HFD) showed a 2.1-fold increase in atherosclerotic lesion of the entire
      aorta compared with those of ND-fed dams (O-ND). Although mRNA expressions of
      interleukin-6, tumor necrosis factor, and monocyte chemotactic protein-1 and
      accumulation of macrophages in epididymal white adipose tissue were less in O-HFD
      than in O-ND, thoracic periaortic adipose tissue (tPAT) showed an exaggerated
      inflammatory response in O-HFD. Intra-abdominal transplantation of tPAT from 8
      week-old O-HFD alongside the distal abdominal aorta exaggerated atherosclerosis
      development of the infrarenal aorta in recipient apolipoprotein E-deficient mice
      compared with tPAT from O-ND (210%, P<0.01). Although macrophage accumulation was
      rarely detected in tPAT of 8-week-old offspring, mRNA expression and protein
      levels of macrophage colony-stimulating factor were markedly elevated in O-HFD
      (2.3-fold, 3.3-fold, respectively, P<0.05), suggesting that increased macrophage
      colony-stimulating factor expression contributes to the augmented accumulation of
      macrophages, followed by the enhanced proinflammatory response. CONCLUSIONS: Our
      findings demonstrate that maternal HFD exaggerates atherosclerosis development in
      offspring by augmenting tPAT-specific inflammatory response proceeded by an
      increased expression of macrophage colony-stimulating factor.

PMID- 25593134
TI  - Effect of decompressive craniectomy on outcome following subarachnoid hemorrhage
      in mice.
AB  - BACKGROUND AND PURPOSE: Elevated intracranial pressure (ICP) is a key feature of
      subarachnoid hemorrhage (SAH). Here, we examined the role of elevated ICP in the
      pathophysiology of SAH, and we investigated whether decreasing ICP by performing
      decompressive craniectomy (DC) can improve outcome. METHODS: SAH was induced in
      male C57BL/6 mice via endovascular Circle of Willis perforation in the following
      4 groups: sham surgery, SAH, DC after SAH, and DC before SAH. DC was performed
      either 15 minutes before or after SAH induction. ICP, cerebral blood flow, heart
      rate, oxygen saturation, and end-tidal PCO2 were monitored for 45 minutes. After
      surgery, neurological function was evaluated daily for 7 days. After killing,
      hippocampal neurons, corpus callosum thickness, and ventricular volume were
      evaluated on paraformaldehyde-fixed coronal brain sections. RESULTS: Although DC
      reduced SAH-induced ICP, it yielded no beneficial effect with respect to
      posthemorrhagic hypoperfusion; moreover, DC increased the incidence of
      rebleeding, induced more severe neurological impairments, and caused higher
      mortality. Post SAH, mice that survived 7 days had no histopathologic
      differences, regardless of whether DC was performed. CONCLUSIONS: Performing DC
      to reduce ICP either during or acutely after SAH resulted in more severe
      bleeding, a higher incidence of rebleeding, and poorer outcome. Thus, elevated
      post-hemorrhagic ICP plays an important role in controlling bleeding after SAH
      and should therefore not be reduced acutely. If DC is considered for treating a
      patient with SAH, the timing of decompression should take these effects into
      consideration.

PMID- 25593132
TI  - Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome.
AB  - OBJECTIVE: Marfan's syndrome is characterized by the formation of ascending
      aortic aneurysms resulting from altered assembly of extracellular matrix
      microfibrils and chronic tissue growth factor (TGF)-beta signaling. TGF-beta is a
      potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We
      hypothesized that as a result of the chronic TGF-beta signaling, VSMC would alter
      their basal differentiation phenotype, which could facilitate the formation of
      aneurysms. This study explores whether Marfan's syndrome entails phenotypic
      alterations of VSMC and possible mechanisms at the subcellular level. APPROACH
      AND RESULTS: Immunohistochemical and Western blotting analyses of dilated aortas
      from Marfan patients showed overexpression of contractile protein markers (alpha
      smooth muscle actin, smoothelin, smooth muscle protein 22 alpha, and calponin-1)
      and collagen I in comparison with healthy aortas. VSMC explanted from Marfan
      aortic aneurysms showed increased in vitro expression of these phenotypic markers
      and also of myocardin, a transcription factor essential for VSMC-specific
      differentiation. These alterations were generally reduced after pharmacological
      inhibition of the TGF-beta pathway. Marfan VSMC in culture showed more robust
      actin stress fibers and enhanced RhoA-GTP levels, which was accompanied by
      increased focal adhesion components and higher nuclear localization of myosin
      related transcription factor A. Marfan VSMC and extracellular matrix measured by
      atomic force microscopy were both stiffer than their respective controls.
      CONCLUSIONS: In Marfan VSMC, both in tissue and in culture, there are variable
      TGF-beta-dependent phenotypic changes affecting contractile proteins and collagen
      I, leading to greater cellular and extracellular matrix stiffness. Altogether,
      these alterations may contribute to the known aortic rigidity that precedes or
      accompanies Marfan's syndrome aneurysm formation.

PMID- 25593136
TI  - History of Hollenhorst plaques.

PMID- 25593135
TI  - Outcome in patients previously on antithrombotic therapy in the SAMMPRIS trial:
      subgroup analysis.
AB  - BACKGROUND AND PURPOSE: Stenting has been used as a rescue therapy in patients
      with intracranial arterial stenosis and a transient ischemic attack or stroke
      when on antithrombotic therapy (AT). We determined whether the stenting versus
      aggressive medical therapy for intracranial arterial stenosis (SAMMPRIS) trial
      supported this approach by comparing the treatments within subgroups of patients
      whose qualifying event (QE) occurred on versus off of AT. METHODS: The primary
      outcome, 30-day stroke and death and later strokes in the territory of the
      qualifying artery, was compared between (1) percutaneous transluminal angioplasty
      and stenting plus aggressive medical therapy (PTAS) versus aggressive medical
      management therapy alone (AMM) for patients whose QE occurred on versus off AT
      and between (2) patients whose QE occurred on versus off AT separately for the
      treatment groups. RESULTS: Among the 284/451 (63%) patients who had their QE on
      AT, the 2-year primary end point rates were 15.6% for those randomized to AMM
      (n=140) and 21.6% for PTAS (n=144; P=0.043, log-rank test). In the 167 patients
      not on AT, the 2-year primary end point rates were 11.6% for AMM (n=87) and 18.8%
      for PTAS (n=80; P=0.31, log-rank test). Within both treatment groups, there was
      no difference in the time to the primary end point between patients who were on
      or off AT (AMM, P=0.96; PTAS, P=0.52; log-rank test). CONCLUSIONS: SAMMPRIS
      results indicate that the benefit of AMM over PTAS is similar in patients on
      versus off AT at the QE and that failure of AT is not a predictor of increased
      risk of a primary end point. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

PMID- 25593137
TI  - Centers for medicare and medicaid services medicare data and stroke research:
      goldmine or landmine?

PMID- 25593139
TI  - Dietary bioactives: establishing a scientific framework for recommended intakes.
AB  - In the United States, dietary reference intakes describe the relations between
      nutrient intakes and indicators of adequacy, prevention of disease, and avoidance
      of excessive intakes among healthy populations for essential nutrients but not
      dietary bioactive components (DBCs), whose absence from the diet is presumably
      not deleterious to health (i.e., does not cause a deficiency syndrome). An
      appropriate framework is needed for establishing recommended intakes for which
      public health messages and food labeling for DBCs can be derived, because their
      putative health benefits may not be readily defined in the context of nutritional
      essentiality. In addition, a myriad of factors make determining their intake and
      status and investigating their discrete contributions to health particularly
      challenging. Therefore, the ASN Dietary Bioactive Components Research Interest
      Section felt it worthwhile to convene a special "hot topic" session at the 2014
      Experimental Biology meeting to discuss this issue and serve as a call for future
      scientific dialogue on establishing a framework for recommended intakes of DBCs.
      This session summary captures the discussions and presentations that transpired
      during this session. 

PMID- 25593138
TI  - Deficiency of brain ATP-binding cassette transporter A-1 exacerbates blood-brain
      barrier and white matter damage after stroke.
AB  - BACKGROUND AND PURPOSE: The ATP-binding cassette transporter A-1 (ABCA1) gene is
      a key target of the transcription factors liver X receptors. Liver X receptor
      activation has anti-inflammatory and neuroprotective effects in animal ischemic
      stroke models. Here, we tested the hypothesis that brain ABCA1 reduces blood
      brain barrier (BBB) and white matter (WM) impairment in the ischemic brain after
      stroke. METHODS: Adult brain-specific ABCA1-deficient (ABCA1(-B/-B)) and floxed
      control (ABCA1(fl/fl)) mice were subjected to permanent distal middle cerebral
      artery occlusion and were euthanized 7 days after distal middle cerebral artery
      occlusion. Functional outcome, infarct volume, BBB leakage, and WM damage were
      analyzed. RESULTS: Compared with ABCA1(fl/fl) mice, ABCA1(-B/-B) mice showed
      marginally (P=0.052) increased lesion volume but significantly increased BBB
      leakage and WM damage in the ischemic brain and more severe neurological
      deficits. Brain ABCA1-deficient mice exhibited increased the level of matrix
      metalloproteinase-9 and reduced the level of insulin-like growth factor 1 in the
      ischemic brain. BBB leakage was inversely correlated (r=-0.073; P<0.05) with
      aquaporin-4 expression. Reduction of insulin-like growth factor 1 and aquaporin
      4, but upregulation of matrix metalloproteinase-9 expression were also found in
      the primary astrocyte cultures derived from ABCA1(-B/-B) mice. Cultured primary
      cortical neurons derived from C57BL/6 wild-type mice with ABCA1(-B/-B) astrocyte
      conditioned medium exhibited decreased neurite outgrowth compared with culture
      with ABCA1(fl/fl) astrocyte-conditioned medium. ABCA1(-B/-B) primary cortical
      neurons show significantly decreased neurite outgrowth, which was attenuated by
      insulin-like growth factor 1 treatment. CONCLUSIONS: We demonstrate that brain
      ABCA1 deficiency increases BBB leakage, WM/axonal damage, and functional deficits
      after stroke. Concomitant reduction of insulin-like growth factor 1 and
      upregulation of matrix metalloproteinase-9 may contribute to brain ABCA1
      deficiency-induced BBB and WM/axonal damage in the ischemic brain.

PMID- 25593141
TI  - What current literature tells us about sustainable diets: emerging research
      linking dietary patterns, environmental sustainability, and economics.
AB  - The concept of sustainable diets, although not new, is gaining increased
      attention across the globe, especially in relation to projected population growth
      and growing concerns about climate change. As defined by the FAO (Proceedings of
      the International Scientific Symposium, Biodiversity and Sustainable Diets 2010;
      FAO 2012), "Sustainable diets are those diets with low environmental impacts
      which contribute to food and nutrition security and to healthy life for present
      and future generations." Consistent and credible science that brings together
      agriculture, food systems, nutrition, public health, environment, economics,
      culture, and trade is needed to identify synergies and trade-offs and to inform
      guidance on vital elements of healthy, sustainable diets. The aim of this article
      is to review the emerging research on environmental and related economic impacts
      of dietary patterns, including habitual eating patterns, nutritionally balanced
      diets, and a variety of different dietary scenarios. Approaches to research
      designs, methodologies, and data sources are compared and contrasted to identify
      research gaps and future research needs. To date, it is difficult to assimilate
      all of the disparate approaches, and more concerted efforts for multidisciplinary
      studies are needed. 

PMID- 25593140
TI  - Understanding nutritional epidemiology and its role in policy.
AB  - Nutritional epidemiology has recently been criticized on several fronts,
      including the inability to measure diet accurately, and for its reliance on
      observational studies to address etiologic questions. In addition, several recent
      meta-analyses with serious methodologic flaws have arrived at erroneous or
      misleading conclusions, reigniting controversy over formerly settled debates. All
      of this has raised questions regarding the ability of nutritional epidemiologic
      studies to inform policy. These criticisms, to a large degree, stem from a
      misunderstanding of the methodologic issues of the field and the inappropriate
      use of the drug trial paradigm in nutrition research. The exposure of interest in
      nutritional epidemiology is human diet, which is a complex system of interacting
      components that cumulatively affect health. Consequently, nutritional
      epidemiology constantly faces a unique set of challenges and continually develops
      specific methodologies to address these. Misunderstanding these issues can lead
      to the nonconstructive and sometimes naive criticisms we see today. This article
      aims to clarify common misunderstandings of nutritional epidemiology, address
      challenges to the field, and discuss the utility of nutritional science in
      guiding policy by focusing on 5 broad questions commonly asked of the field. 

PMID- 25593143
TI  - Anthropometric measurements and dental caries in children: a systematic review of
      longitudinal studies.
AB  - There is growing interest in the association between anthropometric measurements
      and dental caries in childhood over time (life-course studies). The aim of this
      review was to identify and systematically review the evidence of the association
      between anthropometric measurements and dental caries in childhood over time.
      PubMed, Institute for Scientific Information (ISI) Web of Knowledge, the Cochrane
      Library, and 6 other databases were searched to identify effective articles. A
      systematic approach involving critical appraisal was conducted to examine the
      relation between anthropometric measurements and dental caries in preschool- and
      school-aged populations from longitudinal studies. An initial search identified
      1338 studies, with 59 potentially effective studies (kappa = 0.82) and 17
      effective studies (kappa = 0.88). The quality of reporting among the studies
      ranged from 19.5 to 30.0 according to the Strengthening the Reporting of
      Observational studies in Epidemiology (STROBE) criteria. Among the effective
      studies, 2 studies in which caries was used to predict anthropometric
      measurements consistently found an inverse association and 15 studies in which
      anthropometric measurements were used to predict caries were inconsistent, with
      results appearing to be influenced by nonuniformity of assessments, setting, and
      procedure of measurements; age and ethnicity of participants; and confounders of
      dental caries. In conclusion, among >1000 studies identified, 17 informed this
      systematic review. The quality of reporting of these studies varied considerably.
      Evidence of the association between anthropometric measurements and dental caries
      is conflicting and remains inconclusive. 

PMID- 25593142
TI  - A review and critical analysis of the scientific literature related to 100% fruit
      juice and human health.
AB  - The association between the consumption of pure (100%) fruit juice (PFJ) and
      human health is uncertain. The current review summarizes data published between
      1995 and 2012 related to PFJ with a focus on juices that are widely available and
      studied in forms representing native juice without supplemental nutrients or
      enhanced phytochemical content. The effects of apple, cranberry, grape,
      grapefruit, orange, and pomegranate PFJ intake on outcomes linked to cancer,
      cardiovascular disease, cognition, hypertension, inflammation, oxidation,
      platelet function, urinary tract infection, and vascular reactivity are reviewed.
      Implications for bodyweight regulation are also addressed. The collective data
      are provocative although challenges and unanswered questions remain. There are
      many plausible mechanisms by which PFJ might be protective, and investigation of
      its effects on human health and disease prevention must remain an active area of
      research. 

PMID- 25593145
TI  - Dietary selenium in adjuvant therapy of viral and bacterial infections.
AB  - Viral and bacterial infections are often associated with deficiencies in
      macronutrients and micronutrients, including the essential trace element
      selenium. In selenium deficiency, benign strains of Coxsackie and influenza
      viruses can mutate to highly pathogenic strains. Dietary supplementation to
      provide adequate or supranutritional selenium supply has been proposed to confer
      health benefits for patients suffering from some viral diseases, most notably
      with respect to HIV and influenza A virus (IAV) infections. In addition, selenium
      containing multimicronutrient supplements improved several clinical and lifestyle
      variables in patients coinfected with HIV and Mycobacterium tuberculosis.
      Selenium status may affect the function of cells of both adaptive and innate
      immunity. Supranutritional selenium promotes proliferation and favors
      differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus
      supporting the acute cellular immune response, whereas excessive activation of
      the immune system and ensuing host tissue damage are counteracted through
      directing macrophages toward the M2 phenotype. This review provides an up-to-date
      overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV,
      hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M.
      tuberculosis, Helicobacter pylori). Data from epidemiologic studies and
      intervention trials, with selenium alone or in combination with other
      micronutrients, and animal experiments are discussed against the background of
      dietary selenium requirements to alter immune functions. 

PMID- 25593146
TI  - Nutrition competencies in health professionals' education and training: a new
      paradigm.
AB  - Most health care professionals are not adequately trained to address diet and
      nutrition-related issues with their patients, thus missing important
      opportunities to ameliorate chronic diseases and improve outcomes in acute
      illness. In this symposium, the speakers reviewed the status of nutrition
      education for health care professionals in the United States, United Kingdom, and
      Australia. Nutrition education is not required for educating and training
      physicians in many countries. Nutrition education for the spectrum of health care
      professionals is uncoordinated, which runs contrary to the current theme of
      interprofessional education. The central role of competencies in guiding medical
      education was emphasized and the urgent need to establish competencies in
      nutrition-related patient care was presented. The importance of additional
      strategies to improve nutrition education of health care professionals was
      highlighted. Public health legislation such as the Patient Protection and
      Affordable Care Act recognizes the role of nutrition, however, to capitalize on
      this increasing momentum, health care professionals must be trained to deliver
      needed services. Thus, there is a pressing need to garner support from
      stakeholders to achieve this goal. Promoting a research agenda that provides
      outcome-based evidence on individual and public health levels is needed to
      improve and sustain effective interprofessional nutrition education. 

PMID- 25593144
TI  - Flavonoid-based therapies in the early management of neurodegenerative diseases.
AB  - During the past several years, there has been enormous progress in the
      understanding of the causative factors that initiate neuronal damage in various
      neurodegenerative diseases, including Alzheimer disease, Parkinson disease,
      multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease.
      Preventing neuronal damage and neuronal death will have a huge clinical benefit.
      However, despite major advances in causative factors that trigger these
      neurodegenerative diseases, to date there have been no therapies available that
      benefit patients who suffer from these diseases. Because most neurodegenerative
      diseases are late-onset and remain asymptomatic for most of the phases, the
      therapies initiated in advanced stages of the disease have limited value to
      patients. It may be possible to prevent or halt the disease progression to a
      great extent if therapies start at the initial stage of the disease. Such
      therapies may restore neuronal function by reducing or even eliminating the
      primary stressor. Flavonoids are key compounds for the development of a new
      generation of therapeutic agents that are clinically effective in treating
      neurodegenerative diseases. Regular consumption of flavonoids has been associated
      with a reduced risk of neurodegenerative diseases. In addition to their
      antioxidant properties, these polyphenolic compounds exhibit neuroprotective
      properties by their interaction with cellular signaling pathways followed by
      transcription and translation that mediate cell function under both normal and
      pathologic conditions. This review focuses on human intervention studies as well
      as animal studies on the role of various flavonoids in the prevention of
      neurodegenerative diseases. 

PMID- 25593147
TI  - Applications of systems science in biomedical research regarding obesity and
      noncommunicable chronic diseases: opportunities, promise, and challenges.
AB  - Interest in the application of systems science (SS) in biomedical research,
      particularly regarding obesity and noncommunicable chronic disease (NCD)
      research, has been growing rapidly over the past decade. SS is a broad term
      referring to a family of research approaches that include modeling. As an
      emerging approach being adopted in public health, SS focuses on the complex
      dynamic interaction between agents (e.g., people) and subsystems defined at
      different levels. SS provides a conceptual framework for interdisciplinary and
      transdisciplinary approaches that address complex problems. SS has unique
      advantages for studying obesity and NCD problems in comparison to the traditional
      analytic approaches. The application of SS in biomedical research dates back to
      the 1960s with the development of computing capacity and simulation software. In
      recent decades, SS has been applied to addressing the growing global obesity
      epidemic. There is growing appreciation and support for using SS in the public
      health field, with many promising opportunities. There are also many challenges
      and uncertainties, including methodologic, funding, and institutional barriers.
      Integrated efforts by stakeholders that address these challenges are critical for
      the successful application of SS in the future. 

PMID- 25593149
TI  - Caffeine intake from food and beverage sources and trends among children and
      adolescents in the United States: review of national quantitative studies from
      1999 to 2011.
AB  - There is increasing concern about potential adverse effects of caffeine in
      children. Our understanding of caffeine intake relies on studies dating to the
      late 1990s. This article synthesizes information from national studies since then
      to describe caffeine consumption, its association with sociodemographic factors,
      key dietary sources including caffeine-containing energy drinks (CCEDs), and
      trends in caffeine intake and sources among US children. Findings from the Kanter
      Worldpanel (KWP) Beverage Consumption Panel and the NHANES showed that caffeine
      consumption prevalence was generally consistent across studies and over time;
      more than one-half of 2- to 5-y-olds and ~75% of older children (>5 y) consumed
      caffeine. The usual intakes of caffeine were 25 and 50 mg/d for children and
      adolescents aged 2-11 and 12-17 y, respectively (NHANES 2007-2010). Caffeine
      consumption correlated with age and was higher in non-Hispanic white children.
      The key sources of caffeine were soda and tea as well as flavored dairy (for
      children aged <12 y) and coffee (for those aged >=12 y). The frequency of CCED
      use varied (2-30%) depending on study setting, methods, and demographic
      characteristics. A statistically significant but small decline in caffeine intake
      was noted in children overall during the 10- to 12-y period examined; intakes
      remained stable among older children (>=12 y). A significant increasing trend in
      CCED and coffee consumption and a decline in soda intake were noted (1999-2010).
      In 2009-2010, 10% of 12- to 19-y-olds and 10-25% of caffeine consumers (aged 12
      19 y) had intakes exceeding Canadian maximal guidelines. Continued monitoring can
      help better understand changes in caffeine consumption patterns of youth. 

PMID- 25593148
TI  - Can energy drinks increase the desire for more alcohol?
AB  - Energy drinks, the fastest growing segment in the beverage market, have become
      popular mixers with alcohol. The emerging research examining the use of alcohol
      mixed with energy drinks (AmEDs) indicates that the combination of caffeine
      containing energy drinks with alcohol may be riskier than the use of alcohol
      alone. The public health concerns arising from AmED use are documented in
      different research domains. Epidemiologic studies reveal that the consumption of
      AmEDs is frequent among young and underage drinkers, demographic groups that are
      more likely to experience the harms and hazards associated with alcohol use. In
      addition, for all consumers, elevated rates of binge drinking and risk of alcohol
      dependence have been associated with AmED use when compared to alcohol alone.
      Results from laboratory studies help explain why AmED use is associated with
      excessive intake of alcohol. When an energy drink (or caffeine) is combined with
      alcohol, the desire (or urge) to drink more alcohol is more pronounced in both
      humans and animals than with the same dose of alcohol alone. The experience of
      drinking alcohol appears to be more rewarding when combined with energy drinks.
      Given that caffeine in other foods and beverages increases preference for those
      products, further research on AmEDs may elucidate the underlying mechanisms that
      contribute to alcohol dependence. 

PMID- 25593152
TI  - Vitamin B-6.

PMID- 25593150
TI  - Human milk: mother nature's prototypical probiotic food?
AB  - The concept of "probiotic" is generally attributed to Dr. Ilya Mechnikov, who
      hypothesized that longevity could be enhanced by manipulating gastrointestinal
      microbes using naturally fermented foods. In 2001, a report of the FAO and WHO
      (2001 Oct, http://www.who.int/foodsafety/publications/fs_
      management/en/probiotics.pdf) proposed a more restrictive definition of
      probiotic, as follows: "a live micro-organism which, when administered in
      adequate amounts, confers a health benefit on the host." As such, answering the
      fundamental question posed here-"Is human milk a probiotic?"-requires first
      grappling with the concept and meaning of the term probiotic. Nonetheless, one
      must also be convinced that human milk contains bacteria. Indeed, there are
      scores of publications providing evidence of a paradigm shift in this regard.
      Variation in the human-milk microbiome may be associated with maternal weight,
      mode of delivery, lactation state, gestation age, antibiotic use, and maternal
      health. Milk constituents (e.g., fatty acids and complex carbohydrates) might
      also be related to the abundance of specific bacterial taxa in milk. Whether
      these bacteria affect infant health is likely, but more studies are needed to
      test this hypothesis. In summary, a growing literature suggests that human milk,
      like all other fluids produced by the body, indeed contains viable bacteria. As
      such, and recognizing the extensive literature relating breastfeeding to optimal
      infant health, we propose that human milk should be considered a probiotic food.
      Determining factors that influence which bacteria are present in milk and if and
      how they influence the mother's and/or the recipient infant's health remain basic
      science and public health realms in which almost nothing is known. 

PMID- 25593151
TI  - Fortification and health: challenges and opportunities.
AB  - Fortification is the process of adding nutrients or non-nutrient bioactive
      components to edible products (e.g., food, food constituents, or supplements).
      Fortification can be used to correct or prevent widespread nutrient intake
      shortfalls and associated deficiencies, to balance the total nutrient profile of
      a diet, to restore nutrients lost in processing, or to appeal to consumers
      looking to supplement their diet. Food fortification could be considered as a
      public health strategy to enhance nutrient intakes of a population. Over the past
      century, fortification has been effective at reducing the risk of nutrient
      deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the
      world today is very different from when fortification emerged in the 1920s.
      Although early fortification programs were designed to eliminate deficiency
      diseases, current fortification programs are based on low dietary intakes rather
      than a diagnosable condition. Moving forward, we must be diligent in our approach
      to achieving effective and responsible fortification practices and policies,
      including responsible marketing of fortified products. Fortification must be
      applied prudently, its effects monitored diligently, and the public informed
      effectively about its benefits through consumer education efforts. Clear lines of
      authority for establishing fortification guidelines should be developed and
      should take into account changing population demographics, changes in the food
      supply, and advances in technology. This article is a summary of a symposium
      presented at the ASN Scientific Sessions and Annual Meeting at Experimental
      Biology 2014 on current issues involving fortification focusing primarily on the
      United States and Canada and recommendations for the development of responsible
      fortification practices to ensure their safety and effectiveness. 

PMID- 25593153
TI  - World Health Organization. Comprehensive Implementation Plan on Maternal, Infant,
      and Young Child Nutrition. Geneva, Switzerland, 2014.

PMID- 25593157
TI  - Annexin A2 is involved in the production of classical swine fever virus
      infectious particles.
AB  - Annexin A2 (ANXA2) is an important host factor regulating several key processes
      in many viruses. To evaluate the potential involvement of ANXA2 in the life cycle
      of classical swine fever virus (CSFV), an RNA interference (RNAi) approach was
      utilized. Knockdown of ANXA2 did not impair CSFV RNA replication but
      significantly reduced CSFV production. A comparable reduction of extracellular
      and intracellular infectivity levels was detected, indicating that ANXA2 might
      play a role in CSFV assembly rather than in genome replication and virion
      release. Furthermore, ANXA2 was found to bind CSFV NS5A, an essential replicase
      component. Amino acids R338, N359, G378 of NS5A were revealed to be pivotal for
      the ANXA2-NS5A interaction. Substitutions of these amino acids had no effect on
      viral RNA replication but substantially reduced CSFV production, which might
      partly be due to these mutations destroying the ANXA2-NS5A interaction. These
      results suggested that ANXA2 might participate in CSFV production process by
      binding NS5A.

PMID- 25593156
TI  - Candy consumption patterns, effects on health, and behavioral strategies to
      promote moderation: summary report of a roundtable discussion.
AB  - Nearly all Americans (97%) report eating candy at least once per year; yet, on a
      given day, only approximately one-fourth of the US population aged >=2 y consumes
      candy. Among all Americans, candy contributes a relatively small proportion of
      calories, added sugars, and saturated fat to the total diet, and recent research
      suggests that current levels of candy consumption are not associated with risk of
      weight gain and cardiovascular disease in children and adults. Providing guidance
      for the consumption of candy in moderation requires an understanding of various
      behavioral health-related factors that influence candy consumption. A roundtable
      of behavioral nutrition experts, researchers, and nutrition educators met to
      discuss recent data on intakes of candy, health outcomes associated with usual
      candy intake, and the impact of behavioral strategies, including restriction,
      education, and environmental awareness, on modifying eating behaviors to achieve
      moderate intakes of candy. Restricting access to palatable foods, whether self
      imposed or by parental control, may have potentially negative consequences.
      Techniques and insight into how to adopt "moderation" in candy consumption, from
      effective parental practices to environmental strategies that facilitate behavior
      change without a high degree of effort, were identified as important next steps
      toward sustainable dietary guidance related to the role of candy and other treats
      in a healthy lifestyle. 

PMID- 25593158
TI  - Clinical signs, pathology and dose-dependent survival of adult wood frogs, Rana
      sylvatica, inoculated orally with frog virus 3 Ranavirus sp., Iridoviridae.
AB  - Amphibian populations suffer massive mortalities from infection with frog virus 3
      FV3, genus Ranavirus, family Iridoviridae, a pathogen also involved in
      mortalities of fish and reptiles. Experimental oral infection with FV3 in captive
      raised adult wood frogs, Rana sylvatica Lithobates sylvaticus, was performed as
      the first step in establishing a native North American animal model of ranaviral
      disease to study pathogenesis and host response. Oral dosing was successful LD50
      was 10(2.93 2.423.44) p.f.u. for frogs averaging 35mm in length. Onset of
      clinical signs occurred 614days post-infection p.i. median 11 days p.i. and time
      to death was 1014 days p.i. median 12 days p.i.. Each tenfold increase in virus
      dose increased the odds of dying by 23-fold and accelerated onset of clinical
      signs and death by approximately 15. Ranavirus DNA was demonstrated in skin and
      liver of all frogs that died or were euthanized because of severe clinical signs.
      Shedding of virus occurred in faeces 710 days p.i. 34.5days before death and skin
      sheds 10 days p.i. 01.5days before death of some frogs dead from infection. Most
      common lesions were dermal erosion and haemorrhages haematopoietic necrosis in
      bone marrow, kidney, spleen and liver and necrosis in renal glomeruli, tongue,
      gastrointestinal tract and urinary bladder mucosa. Presence of ranavirus in
      lesions was confirmed by immunohistochemistry. Intracytoplasmic inclusion bodies
      probably viral were present in the bone marrow and the epithelia of the oral
      cavity, gastrointestinal tract, renal tubules and urinary bladder. Our work
      describes a ranaviruswood frog model and provides estimates that can be
      incorporated into ranavirus disease ecology models.

PMID- 25593159
TI  - Phylogenetically distinct equine influenza viruses show different tropism for the
      swine respiratory tract.
AB  - Influenza A viruses circulate in a wide range of animals. H3N8 equine influenza
      virus (EIV) is an avian-origin virus that has established in dogs as canine
      influenza virus (CIV) and has also been isolated from camels and pigs. Previous
      work suggests that mutations acquired during EIV evolution might have played a
      role in CIV emergence. Given the potential role of pigs as a source of human
      infections, we determined the ability of H3N8 EIVs to replicate in pig cell lines
      and in respiratory explants. We show that phylogenetically distinct EIVs display
      different infection phenotypes along the pig respiratory tract, but not in cell
      lines. Our results suggest that EIV displays a dynamic host range along its
      evolutionary history, supporting the view that evolutionary processes play
      important roles in host range and tropism and also underscoring the utility of
      using explant cultures to study influenza pathogenesis.

PMID- 25593160
TI  - Construction of an infectious cDNA clone of genotype 1 avian hepatitis E virus:
      characterization of its pathogenicity in broiler breeders and demonstration of
      its utility in studying the role of the hypervariable region in virus
      replication.
AB  - A full-length infectious cDNA clone of the genotype 1 Korean avian hepatitis E
      virus (avian HEV) (pT11-aHEV-K) was constructed and its infectivity and
      pathogenicity were investigated in leghorn male hepatoma (LMH) chicken cells and
      broiler breeders. We demonstrated that capped RNA transcripts from the pT11-aHEV
      K clone were translation competent when transfected into LMH cells and infectious
      when injected intrahepatically into the livers of chickens. Gross and microscopic
      pathological lesions underpinned the avian HEV infection and helped characterize
      its pathogenicity in broiler breeder chickens. The avian HEV genome contains a
      hypervariable region (HVR) in ORF1. To demonstrate the utility of the avian HEV
      infectious clone, several mutants with various deletions in and beyond the known
      HVR were derived from the pT11-aHEV-K clone. The HVR-deletion mutants were
      replication competent in LMH cells, although the deletion mutants extending
      beyond the known HVR were non-viable. By using the pT11-aHEV-K infectious clone
      as the backbone, an avian HEV luciferase reporter replicon and HVR-deletion
      mutant replicons were also generated. The luciferase assay results of the
      reporter replicon and its mutants support the data obtained from the infectious
      clone and its derived mutants. To further determine the effect of HVR deletion on
      virus replication, the capped RNA transcripts from the wild-type pT11-aHEV-K
      clone and its mutants were injected intrahepatically into chickens. The HVR
      deletion mutants that were translation competent in LMH cells displayed in
      chickens an attenuation phenotype of avian HEV infectivity, suggesting that the
      avian HEV HVR is important in modulating the virus infectivity and pathogenicity.

PMID- 25593161
TI  - Glycoprotein E of the Japanese encephalitis virus forms virus-like particles and
      induces syncytia when expressed by a baculovirus.
AB  - The prM glycoprotein is thought to be a chaperone for the proper folding,
      membrane association and assembly of the envelope protein (E) of flaviviruses.
      The prM-E and E proteins of the Japanese encephalitis virus (JEV) were expressed
      in insect cells using both the baculovirus-expression system and the transient
      expression method. Protein expression was analysed by Western blotting and the
      cytopathic effect was observed by microscopy. In the baculovirus-expression
      system the E protein, with or without the prM protein, induced syncytial
      formation in Sf9 cells. Transient expression of prM-E also induced syncytia in
      Sf9 cells. Immunofluorescence revealed that in presence of prM, E proteins were
      endoplasmic reticulum-like in distribution, while in the absence of prM, E
      proteins were located on the cell surface. Sucrose gradient sedimentation and
      Western blot analysis indicated that the E protein expressed with or without the
      prM protein was secreted into the culture medium in particulate form. The
      formation of virus-like particles (VLPs) in the medium was confirmed by electron
      microscopy and immunoelectron microscopy. The results suggest that the E protein
      of JEV in the absence of prM, retained its fusion ability, by either cell surface
      expression or formation of VLPs. Moreover, based on the observation that co
      expression of prM-E in Sf9 cells induced considerable syncytial formation, a
      novel, safe and simple antiviral screening approach is proposed for studying
      inhibitory antibodies, peptides or small molecules targeting the JEV E protein.

PMID- 25593162
TI  - Toward designing safer chemicals.

PMID- 25593164
TI  - The Ebola Epidemic. High hopes for Guinean vaccine trial.

PMID- 25593165
TI  - Evolution. All in the (bigger) family.

PMID- 25593166
TI  - Biomedicine. Google[x] searches for ways to boost cancer immunotherapy.

PMID- 25593167
TI  - Iraq. Throwing a lifeline to a one-time Arab science power.

PMID- 25593168
TI  - Science Communication. Backlash greets 'bad luck' cancer study and coverage.

PMID- 25593169
TI  - Solar Cells. Devices team up to boost solar power.

PMID- 25593171
TI  - Geology. The birth of the geological map.

PMID- 25593170
TI  - The cancer stem cell gamble.

PMID- 25593172
TI  - Physics. New SQUID on the Bloch.

PMID- 25593173
TI  - Immunology. Interfering with interferons.

PMID- 25593174
TI  - Social Science. Gender inequality in science.

PMID- 25593175
TI  - Intellectual Property. Disclosing patents' secrets.

PMID- 25593176
TI  - One Medicine One Science and policy.

PMID- 25593177
TI  - Counting on small-scale fisheries.

PMID- 25593178
TI  - A defense of animal welfare accreditation.

PMID- 25593179
TI  - Agriculture facilitated permanent human occupation of the Tibetan Plateau after
      3600 B.P.
AB  - Our understanding of when and how humans adapted to living on the Tibetan Plateau
      at altitudes above 2000 to 3000 meters has been constrained by a paucity of
      archaeological data. Here we report data sets from the northeastern Tibetan
      Plateau indicating that the first villages were established only by 5200 calendar
      years before the present (cal yr B.P.). Using these data, we tested the
      hypothesis that a novel agropastoral economy facilitated year-round living at
      higher altitudes since 3600 cal yr B.P. This successful subsistence strategy
      facilitated the adaptation of farmers-herders to the challenges of global
      temperature decline during the late Holocene. 

PMID- 25593181
TI  - Reduced El Nino-Southern Oscillation during the Last Glacial Maximum.
AB  - El Nino-Southern Oscillation (ENSO) is a major source of global interannual
      variability, but its response to climate change is uncertain. Paleoclimate
      records from the Last Glacial Maximum (LGM) provide insight into ENSO behavior
      when global boundary conditions (ice sheet extent, atmospheric partial pressure
      of CO2) were different from those today. In this work, we reconstruct LGM
      temperature variability at equatorial Pacific sites using measurements of
      individual planktonic foraminifera shells. A deep equatorial thermocline altered
      the dynamics in the eastern equatorial cold tongue, resulting in reduced ENSO
      variability during the LGM compared to the Late Holocene. These results suggest
      that ENSO was not tied directly to the east-west temperature gradient, as
      previously suggested. Rather, the thermocline of the eastern equatorial Pacific
      played a decisive role in the ENSO response to LGM climate. 

PMID- 25593180
TI  - The roller coaster flight strategy of bar-headed geese conserves energy during
      Himalayan migrations.
AB  - The physiological and biomechanical requirements of flight at high altitude have
      been the subject of much interest. Here, we uncover a steep relation between
      heart rate and wingbeat frequency (raised to the exponent 3.5) and estimated
      metabolic power and wingbeat frequency (exponent 7) of migratory bar-headed
      geese. Flight costs increase more rapidly than anticipated as air density
      declines, which overturns prevailing expectations that this species should
      maintain high-altitude flight when traversing the Himalayas. Instead, a "roller
      coaster" strategy, of tracking the underlying terrain and discarding large
      altitude gains only to recoup them later in the flight with occasional benefits
      from orographic lift, is shown to be energetically advantageous for flights over
      the Himalayas. 

PMID- 25593182
TI  - Linked canopy, climate, and faunal change in the Cenozoic of Patagonia.
AB  - Vegetation structure is a key determinant of ecosystems and ecosystem function,
      but paleoecological techniques to quantify it are lacking. We present a method
      for reconstructing leaf area index (LAI) based on light-dependent morphology of
      leaf epidermal cells and phytoliths derived from them. Using this proxy, we
      reconstruct LAI for the Cenozoic (49 million to 11 million years ago) of middle
      latitude Patagonia. Our record shows that dense forests opened up by the late
      Eocene; open forests and shrubland habitats then fluctuated, with a brief middle
      Miocene regreening period. Furthermore, endemic herbivorous mammals show
      accelerated tooth crown height evolution during open, yet relatively grass-free,
      shrubland habitat intervals. Our Patagonian LAI record provides a high
      resolution, sensitive tool with which to dissect terrestrial ecosystem response
      to changing Southern Ocean conditions during the Cenozoic. 

PMID- 25593183
TI  - Expectations of brilliance underlie gender distributions across academic
      disciplines.
AB  - The gender imbalance in STEM subjects dominates current debates about women's
      underrepresentation in academia. However, women are well represented at the Ph.D.
      level in some sciences and poorly represented in some humanities (e.g., in 2011,
      54% of U.S. Ph.D.'s in molecular biology were women versus only 31% in
      philosophy). We hypothesize that, across the academic spectrum, women are
      underrepresented in fields whose practitioners believe that raw, innate talent is
      the main requirement for success, because women are stereotyped as not possessing
      such talent. This hypothesis extends to African Americans' underrepresentation as
      well, as this group is subject to similar stereotypes. Results from a nationwide
      survey of academics support our hypothesis (termed the field-specific ability
      beliefs hypothesis) over three competing hypotheses. 

PMID- 25593186
TI  - Charge ordering in the electron-doped superconductor Nd(2-x)Ce(x)CuO4.
AB  - In cuprate high-temperature superconductors, an antiferromagnetic Mott insulating
      state can be destabilized toward unconventional superconductivity by either hole
      or electron doping. In hole-doped (p-type) cuprates, a charge ordering (CO)
      instability competes with superconductivity inside the pseudogap state. We report
      resonant x-ray scattering measurements that demonstrate the presence of charge
      ordering in the n-type cuprate Nd(2-x)Ce(x)CuO4 near optimal doping. We find that
      the CO in Nd(2-x)Ce(x)CuO4 occurs with similar periodicity, and along the same
      direction, as in p-type cuprates. However, in contrast to the latter, the CO
      onset in Nd(2-x)Ce(x)CuO4 is higher than the pseudogap temperature, and is in the
      temperature range where antiferromagnetic fluctuations are first detected. Our
      discovery opens a parallel path to the study of CO and its relationship to
      antiferromagnetism and superconductivity.

PMID- 25593187
TI  - Semiconductor double quantum dot micromaser.
AB  - The coherent generation of light, from masers to lasers, relies upon the specific
      structure of the individual emitters that lead to gain. Devices operating as
      lasers in the few-emitter limit provide opportunities for understanding quantum
      coherent phenomena, from terahertz sources to quantum communication. Here we
      demonstrate a maser that is driven by single-electron tunneling events.
      Semiconductor double quantum dots (DQDs) serve as a gain medium and are placed
      inside a high-quality factor microwave cavity. We verify maser action by
      comparing the statistics of the emitted microwave field above and below the maser
      threshold. 

PMID- 25593184
TI  - Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR
      inhibitors.
AB  - Cancer cells rely on telomerase or the alternative lengthening of telomeres (ALT)
      pathway to overcome replicative mortality. ALT is mediated by recombination and
      is prevalent in a subset of human cancers, yet whether it can be exploited
      therapeutically remains unknown. Loss of the chromatin-remodeling protein ATRX
      associates with ALT in cancers. Here, we show that ATRX loss compromises cell
      cycle regulation of the telomeric noncoding RNA TERRA and leads to persistent
      association of replication protein A (RPA) with telomeres after DNA replication,
      creating a recombinogenic nucleoprotein structure. Inhibition of the protein
      kinase ATR, a critical regulator of recombination recruited by RPA, disrupts ALT
      and triggers chromosome fragmentation and apoptosis in ALT cells. The cell death
      induced by ATR inhibitors is highly selective for cancer cells that rely on ALT,
      suggesting that such inhibitors may be useful for treatment of ALT-positive
      cancers. 

PMID- 25593188
TI  - Universal solvent restructuring induced by colloidal nanoparticles.
AB  - Colloidal nanoparticles, used for applications from catalysis and energy
      applications to cosmetics, are typically embedded in matrixes or dispersed in
      solutions. The entire particle surface, which is where reactions are expected to
      occur, is thus exposed. Here, we show with x-ray pair distribution function
      analysis that polar and nonpolar solvents universally restructure around
      nanoparticles. Layers of enhanced order exist with a thickness influenced by the
      molecule size and up to 2 nanometers beyond the nanoparticle surface. These
      results show that the enhanced reactivity of solvated nanoparticles includes a
      contribution from a solvation shell of the size of the particle itself. 

PMID- 25593185
TI  - Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection.
AB  - CD4 T cells promote innate and adaptive immune responses, but how vaccine
      elicited CD4 T cells contribute to immune protection remains unclear. We
      evaluated whether induction of virus-specific CD4 T cells by vaccination would
      protect mice against infection with chronic lymphocytic choriomeningitis virus
      (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses
      resulted in catastrophic inflammation and mortality after challenge with a
      persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells
      and was associated with a cytokine storm, generalized inflammation, and multi
      organ system failure. Virus-specific CD8 T cells or antibodies abrogated the
      pathology. These data demonstrate that vaccine-elicited CD4 T cells in the
      absence of effective antiviral immune responses can trigger lethal
      immunopathology. 

PMID- 25593189
TI  - Observation of Fermi arc surface states in a topological metal.
AB  - The topology of the electronic structure of a crystal is manifested in its
      surface states. Recently, a distinct topological state has been proposed in
      metals or semimetals whose spin-orbit band structure features three-dimensional
      Dirac quasiparticles. We used angle-resolved photoemission spectroscopy to
      experimentally observe a pair of spin-polarized Fermi arc surface states on the
      surface of the Dirac semimetal Na3Bi at its native chemical potential. Our
      systematic results collectively identify a topological phase in a gapless
      material. The observed Fermi arc surface states open research frontiers in
      fundamental physics and possibly in spintronics. 

PMID- 25593190
TI  - A European postdoc for the family.

PMID- 25593191
TI  - Marine defaunation: animal loss in the global ocean.
AB  - Marine defaunation, or human-caused animal loss in the oceans, emerged forcefully
      only hundreds of years ago, whereas terrestrial defaunation has been occurring
      far longer. Though humans have caused few global marine extinctions, we have
      profoundly affected marine wildlife, altering the functioning and provisioning of
      services in every ocean. Current ocean trends, coupled with terrestrial
      defaunation lessons, suggest that marine defaunation rates will rapidly intensify
      as human use of the oceans industrializes. Though protected areas are a powerful
      tool to harness ocean productivity, especially when designed with future climate
      in mind, additional management strategies will be required. Overall, habitat
      degradation is likely to intensify as a major driver of marine wildlife loss.
      Proactive intervention can avert a marine defaunation disaster of the magnitude
      observed on land. 

PMID- 25593192
TI  - Implementation of secondary stroke prevention protocol for ischaemic stroke
      patients in primary care.
AB  - OBJECTIVE: To investigate the effectiveness of a secondary stroke prevention
      protocol in the general out-patient clinic. DESIGN: Cohort study with pre- and
      post-intervention comparisons. SETTING: Two general out-patient clinics in Hong
      Kong. PATIENTS: Ischaemic stroke patients who had long-term follow-up in two
      clinics were recruited. The patients of one clinic received the intervention
      (intervention group) and the patients of the second clinic did not receive the
      intervention (control group). The recruitment period lasted for 6 months from 1
      September 2008 to 28 February 2009. The pre-intervention phase data collection
      started within this 6-month period. The protocol implementation started at the
      intervention clinic on 1 April 2009. The post-intervention phase data collection
      started 9 months after the protocol implementation, and ran for 6 months from 1
      January 2010 to 30 June 2010. MAIN OUTCOME MEASURES: Clinical data before and
      after the intervention, including blood pressure, glycated haemoglobin level, low
      density lipoprotein level and prescription pattern, were compared between the two
      groups to see whether there was enhancement of secondary stroke management.
      RESULTS: A total of 328 patients were recruited into the intervention group and
      249 into the control group; data of 256 and 210 patients from these groups were
      analysed, respectively. After intervention, there were significant reductions in
      mean (+/- standard deviation) systolic blood pressure (135.2 +/- 17.5 mm Hg to
      127.7 +/- 12.2 mm Hg), glycated haemoglobin level (7.2 +/- 1.0% to 6.5 +/- 0.8%),
      and low-density lipoprotein level (3.4 +/- 0.8 mmol/L to 2.8 +/- 1.3 mmol/L) in
      the intervention group (all P<0.01). There were no significant reductions in mean
      systolic blood pressure, glycated haemoglobin level, or low-density lipoprotein
      level in the control group. There was a significant increase in statin use
      (P<0.01) in both clinics. CONCLUSION: Through implementation of a clinic
      protocol, the standard of care of secondary stroke prevention for ischaemic
      stroke patients could be improved in a general out-patient clinic.

PMID- 25593193
TI  - Prevention of ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia is the commonest, yet mostly preventable,
      infection in mechanically ventilated patients. Successful control of ventilator
      associated pneumonia can save hospitalisation cost, and is possible by using a
      multidisciplinary clinical and administrative approach. The ventilator-associated
      pneumonia rate should be expressed as the number of ventilator-associated
      pneumonia days per 1000 ventilator days to take into account the device
      utilisation duration for meaningful comparison. Various strategies address the
      issue, including general infection control measures, body positioning, intubation
      and mechanical ventilation, oral and gastro-intestinal tract, endotracheal tube,
      airway pressure, cuff pressure, selective digestive and/or oropharyngeal
      decontamination, and probiotic or early antibiotic treatment, as well as overall
      administration at a policy level. The rationale and controversy of these
      approaches are discussed in this article. The authors suggest that all units
      treating mechanically ventilated patients should have a ventilator-associated
      pneumonia prevention protocol in place, and ventilator-associated pneumonia
      should be seriously considered as a key performance indicator in local intensive
      care units. 

PMID- 25593194
TI  - Screening analysis of ubiquitin ligases reveals G2E3 as a potential target for
      chemosensitizing cancer cells.
AB  - Cisplatin is widely used against various tumors, but resistance is commonly
      encountered. By inducing DNA crosslinks, cisplatin triggers DNA damage response
      (DDR) and cell death. However, the molecular determinants of how cells respond to
      cisplatin are incompletely understood. Since ubiquitination plays a major role in
      DDR, we performed a high-content siRNA screen targeting 327 human ubiquitin
      ligases and 92 deubiquitinating enzymes in U2OS cells, interrogating the response
      to cisplatin. We quantified gammaH2AX by immunofluorescence and image analysis as
      a read-out for DNA damage. Among known mediators of DDR, the screen identified
      the ubiquitin ligase G2E3 as a new player in the response to cisplatin. G2E3
      depletion led to decreased gammaH2AX levels and decreased phosphorylation of the
      checkpoint kinase 1 (Chk1) upon cisplatin. Moreover, loss of G2E3 triggered
      apoptosis and decreased proliferation of cancer cells. Treating cells with the
      nucleoside analogue gemcitabine led to increased accumulation of single-stranded
      DNA upon G2E3 depletion, pointing to a defect in replication. Furthermore, we
      show that endogenous G2E3 levels in cancer cells were down-regulated upon
      chemotherapeutic treatment. Taken together, our results suggest that G2E3 is a
      molecular determinant of the DDR and cell survival, and that its loss sensitizes
      tumor cells towards DNA-damaging treatment. 

PMID- 25593195
TI  - MicroRNA regulation of molecular pathways as a generic mechanism and as a core
      disease phenotype.
AB  - The role of microRNAs as key regulators of a wide variety of fundamental cellular
      processes, such as apoptosis, differentiation, proliferation and cell cycle is
      increasingly recognized in most aspects of biology and biomedicine. Accretion of
      results from multiple microRNA studies over multiple pathway networks, led us to
      hypothesize that microRNAs target molecular pathways. As we show here, this is a
      network-wide phenomenon. The work presented, uses statistical tools that show how
      single microRNAs target molecular pathways. We demonstrate that this targeting
      could not be the result of random associations and cannot be the result of the
      sheer numeracy of microRNA targets. Furthermore, the strongest evidence for the
      association microRNA-pathway, is in a demonstration of the way by which these
      associations are disease-relevant. In our analyses we study ten different types
      of cancer involving thousands of samples, and show that the identified microRNA
      pathway associations demonstrate a clinical affiliation and an ability to
      stratify patients. The work presented here shows the first evidence for a
      mechanism of microRNAs-pathway generic regulation. This regulation is tightly
      associated with clinical phenotype. The presented approach may catalyze targeted
      treatment through exposure of hidden regulatory mechanisms and a systems-medicine
      view of clinical observation. 

PMID- 25593197
TI  - Two hits are better than one: synergistic anticancer activity of alpha-helical
      peptides and doxorubicin/epirubicin.
AB  - This study explored combinational anticancer therapy using alpha-helical peptides
      HPRP-A1/HPRP-A2 with the chemical drugs doxorubicin (DOX) and epirubicin (EPI).
      The in vitro activity of these drugs against different cancer cell lines was
      synergistically increased, as was their activity in a HeLa xenograft model in
      BALB/c nude mice. We delineated the mechanism of this synergy by studying the
      apoptosis pathway and morphologic changes in the HeLa cell membrane. The
      mechanism of the HPRP-A1/DOX combination was found to involve enhanced apoptosis,
      which seemed to be caspase-dependent and involved both the extrinsic and
      intrinsic parts of the caspase cascade in HeLa cells. Combined application of
      HPRP-A1 and DOX at low concentrations was significantly more effective than
      either drug alone against HeLa tumors in the mouse xenograft model. This type of
      combination therapy appears to have great clinical potential. 

PMID- 25593196
TI  - Advances in targeted therapies and new promising targets in esophageal cancer.
AB  - Esophageal cancer, comprising squamous carcinoma and adenocarcinoma, is a leading
      cause of cancer-related death in the world. Notably, the incidence of esophageal
      adenocarcinoma has increased at an alarming rate in the Western world.
      Unfortunately, the standard first-line chemo-radiotherapeutic approaches are
      toxic and of limited efficacy in the treatment of a significant number of cancer
      patients. The molecular analysis of cancer cells has uncovered key genetic and
      epigenetic alterations underlying the development and progression of tumors.
      These discoveries have paved the way for the emergence of targeted therapy
      approaches. This review will highlight recent progress in the development of
      targeted therapies in esophageal cancer. This will include a review of drugs
      targeting receptor tyrosine kinases and other kinases in esophageal cancer.
      Additional studies will be required to develop a rational integration of these
      targeted agents with respect to histologic types of esophageal cancer and the
      optimal selection of cancer patients who would most likely benefit from targeted
      therapy. Identification of AURKA and AXL as key molecular players in esophageal
      tumorigenesis and drug resistance strongly justifies the evaluation of the
      available drugs against these targets in clinical trials. 

PMID- 25593198
TI  - The TLR7 agonist induces tumor regression both by promoting CD4+T cells
      proliferation and by reversing T regulatory cell-mediated suppression via
      dendritic cells.
AB  - Treg-induced immunosuppression is now recognized as a key element in enabling
      tumors to escape immune-mediated destruction. Although topical TLR7 therapies
      such as imiquimod have been proved successful in the treatment of dermatological
      malignancy and a number of conditions beyond the FDA-approved indications, the
      mechanism behind the effect of TLR7 on effector T cell and Treg cell function in
      cancer immunosurveillance is still not well understood. Here, we found that
      Loxoribin, one of the TLR7 ligands, could inhibit tumor growth in xenograft
      models of colon cancer and lung cancer, and these anti-tumor effects of Loxoribin
      were mediated by promoting CD4+T cell proliferation and reversing Treg-mediated
      suppression via dendritic cells (DCs). However, deprivation of IL-6 using a
      neutralizing antibody abrogated the ability of Loxoribin-treated DCs, which
      reversed the Treg cell-mediated suppression. Furthermore, adoptive transfer of
      Loxoribin-treated DCs inhibited the tumor growth in vivo. Thus, this study links
      TLR7 signaling to the functional control of effector T cells and Treg cells and
      identifies Loxoribin as a new therapeutic strategy in cancer treatment, which may
      offer new opportunities to improve the outcome of cancer immunotherapy.

PMID- 25593200
TI  - Dual-lumen balloon catheters may improve liquid embolization of vascular
      malformations: an experimental study in Swine.
AB  - BACKGROUND AND PURPOSE: Liquid embolic agents are increasingly used to treat
      vascular malformations. We sought to assess embolization with these agents by
      using a dual-lumen balloon catheter in an experimental setting. MATERIALS AND
      METHODS: Eighteen injections of liquid embolic agents were performed in the rete
      mirabile of swine. We used 3 methods to control liquid embolic agent reflux: 1)
      dual-lumen balloon-catheter (group A, n = 8); 2) injection of liquid embolic
      agent after proximal n-BCA plug formation through a second microcatheter (group
      B, n = 4); and 3) standard liquid embolic agent injection (group C, controls, n =
      6). The following outcomes were graded by using ordinal scales by angiography,
      macrophotography, and radiography of retia after euthanasia: 1) angiographic and
      pathologic extent of liquid embolic agent embolization of the rete, 2) reflux of
      liquid embolic agents in the parent artery, and 3) density of liquid embolic
      agents in the proximal rete. Technical complications were also recorded. A
      successful injection was defined as an embolization that reached the
      contralateral rete without reflux into proximal external branches. Exact logistic
      regression analyses were performed to compare groups. RESULTS: There were
      significant differences among groups for reflux (P = .029) and liquid embolic
      agent density in the proximal rete (P = .014), while extension to the
      contralateral rete did not reach statistical significance (P = .07). Injections
      differed among groups (P = .004), with dual-lumen balloon-catheter injections
      more frequently successful compared with control injections (P = .019).
      CONCLUSIONS: Dual-lumen balloon catheters allowed better liquid embolic agent
      injections than standard injections.

PMID- 25593199
TI  - A serum microRNA signature associated with complete remission and progression
      after autologous stem-cell transplantation in patients with multiple myeloma.
AB  - We have examined serum microRNA expression in multiple myeloma (MM) patients at
      diagnosis and at complete response (CR) after autologous stem-cell
      transplantation (ASCT), in patients with stable monoclonal gammopathy of
      undetermined significance, and in healthy controls. MicroRNAs were first profiled
      using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then
      validated by individual TaqMan MicroRNA assays and correlated with CR and
      progression-free survival (PFS) after ASCT. Supervised analysis identified a
      differentially expressed 14-microRNA signature. The differential expression of
      miR-16 (P = 0.028), miR-17 (P = 0.016), miR-19b (P = 0.009), miR-20a (P = 0.017)
      and miR-660 (P = 0.048) at diagnosis and CR was then confirmed by individual
      assays. In addition, high levels of miR-25 were related to the presence of
      oligoclonal bands (P = 0.002). Longer PFS after ASCT was observed in patients
      with high levels of miR-19b (6 vs. 1.8 years; P < 0.001) or miR-331 (8.6 vs. 2.9
      years; P = 0.001). Low expression of both miR-19b and miR-331 in combination was
      a marker of shorter PFS (HR 5.3; P = 0.033). We have identified a serum microRNA
      signature with potential as a diagnostic and prognostic tool in MM. 

PMID- 25593201
TI  - Pituitary-Targeted Dynamic Contrast-Enhanced Multisection CT for Detecting MR
      Imaging-Occult Functional Pituitary Microadenoma.
AB  - BACKGROUND AND PURPOSE: Although resection of a tumor by trans-sphenoidal surgery
      is considered the criterion standard for successful surgical treatment of
      functional pituitary microadenoma, MR imaging occasionally fails to visualize and
      identify the tumor and supplementary imaging modalities are necessary. We tested
      the possibility of dynamic contrast-enhanced multisection CT of the pituitary
      gland accompanying image reconstruction of contrast agent dynamics to identify
      the localizations of microadenomas and compared the diagnostic performance with
      conventional pituitary-targeted MR imaging. MATERIALS AND METHODS: Twenty-eight
      patients with surgically confirmed functional pituitary microadenomas (including
      growth hormone-, adrenocorticotropic hormone-, and prolactin-secreting adenomas)
      who underwent pituitary-targeted dynamic contrast-enhanced multisection CT were
      retrospectively investigated. We undertook image reconstruction of the dynamics
      of the contrast agent around the pituitary gland in a voxelwise manner,
      visualizing any abnormality and enabling qualification of contrast dynamics
      within the tumor. RESULTS: Fifteen cases were correctly diagnosed by MR imaging,
      while dynamic contrast-enhanced multisection CT correctly diagnosed 26 cases. The
      accuracy of localization was markedly better for adrenocorticotropic hormone
      secreting microadenomas, increasing from 32% on MR imaging to 85% by dynamic
      contrast-enhanced multisection CT. Compared with the normal pituitary gland,
      adrenocorticotropic hormone-secreting adenoma showed the least difference in
      contrast enhancement of the different functional microadenomas. Images acquired
      at 45-60 seconds after contrast agent injection showed the largest difference in
      contrast enhancement between an adenoma and the normal pituitary gland.
      CONCLUSIONS: Dynamic contrast-enhanced multisection CT combined with image
      reconstruction of the contrast-enhanced dynamics holds promise in detecting MR
      imaging-occult pituitary microadenomas.

PMID- 25593204
TI  - Erratum.

PMID- 25593202
TI  - Diffusion and perfusion MRI to differentiate treatment-related changes including
      pseudoprogression from recurrent tumors in high-grade gliomas with
      histopathologic evidence.
AB  - BACKGROUND AND PURPOSE: Treatment-related changes and recurrent tumors often have
      overlapping features on conventional MR imaging. The purpose of this study was to
      assess the utility of DWI and DSC perfusion imaging alone and in combination to
      differentiate treatment-related effects and recurrent high-grade gliomas.
      MATERIALS AND METHODS: We retrospectively identified 68 consecutive patients with
      high-grade gliomas treated by surgical resection followed by radiation therapy
      and temozolomide, who then developed increasing enhancing mass lesions
      indeterminate for treatment-related changes versus recurrent tumor. All lesions
      were diagnosed by histopathology at repeat surgical resection. ROI analysis was
      performed of the enhancing lesion on the ADC and DSC maps. Measurements made by a
      2D ROI of the enhancing lesion on a single slice were recorded as ADCLesion and
      rCBVLesion, and measurements made by the most abnormal small fixed diameter ROI
      as ADCROI and rCBVROI. Statistical analysis was performed with Wilcoxon rank sum
      tests with P = .05. RESULTS: Ten of the 68 patients (14.7%) had treatment-related
      changes, while 58 patients (85.3%) had recurrent tumor only (n = 19) or recurrent
      tumor mixed with treatment effect (n = 39). DWI analysis showed higher ADCLesion
      in treatment-related changes than in recurrent tumor (P = .003). DSC analysis
      revealed lower relative cerebral blood volume (rCBV)Lesion and rCBVROI in
      treatment-related changes (P = .003 and P = .011, respectively). Subanalysis of
      patients with suspected pseudoprogression also revealed higher ADCLesion (P =
      .001) and lower rCBVLesion (P = .028) and rCBVROI (P = .032) in treatment-related
      changes. Applying a combined ADCLesion and rCBVLesion model did not outperform
      either the ADC or rCBV metric alone. CONCLUSIONS: Treatment-related changes
      showed higher diffusion and lower perfusion than recurrent tumor. Similar
      correlations were found for patients with suspected pseudoprogression.

PMID- 25593203
TI  - Reversible Cerebral Vasoconstriction Syndrome, Part 1: Epidemiology,
      Pathogenesis, and Clinical Course.
AB  - Reversible cerebral vasoconstriction syndrome is a clinical and radiologic
      syndrome that represents a common presentation of a diverse group of disorders.
      The syndrome is characterized by thunderclap headache and reversible
      vasoconstriction of cerebral arteries, which can either be spontaneous or related
      to an exogenous trigger. The pathophysiology of reversible cerebral
      vasoconstriction syndrome is unknown, though alterations in cerebral vascular
      tone are thought to be a key underlying mechanism. The syndrome typically follows
      a benign course; however, reversible cerebral vasoconstriction syndrome may
      result in permanent disability or death in a small minority of patients secondary
      to complications such as ischemic stroke or intracranial hemorrhage. 

PMID- 25593205
TI  - Brain perfusion and vasoreactivity in multiple sclerosis.

PMID- 25593206
TI  - Uncertainty and agreement regarding the role of flow diversion in the management
      of difficult aneurysms.
AB  - BACKGROUND AND PURPOSE: The role of flow diversion in the management of aneurysms
      remains unknown. We sought to evaluate the community agreement regarding
      indications for flow diversion. MATERIALS AND METHODS: A portfolio of 35
      difficult aneurysm cases was sent to 40 clinicians with varying backgrounds and
      experience. Responders were asked whether they considered flow diversion a
      treatment option, whether other options were possible, whether recruitment in a
      randomized trial would be considered, and to select their final choice. Agreement
      was studied by using kappa statistics. RESULTS: Decisions for flow diversion were
      more frequent (n = 300, 39%) than decisions to coil (n = 163, 21.2%), to observe
      (n = 121, 15.7%), to occlude the parent vessel (n = 102, 13.2%), or to clip (n =
      66, 8.6%). Sidewall aneurysm morphology was associated with flow diversion as the
      final choice (P = .001). Interjudge agreement was fair at best (kappa <0.3) for
      all cases and all judges, despite high certainty levels (range, 7.2-8.9 +/- 2.0
      on a 0-10 scale). Agreement was no better within specialties or with more
      experience. All patients were judged to have other treatment options. Judges were
      willing to offer trial participation in 417 of 741 (56.3%) scenarios, more
      frequently when the aneurysm was sidewall (P = .001) or in the anterior
      circulation (P = .028). CONCLUSIONS: Individuals did not agree regarding the
      indications for flow diversion. There is sufficient uncertainty to justify trials
      designed to protect patients from the potential risks of premature adoption of an
      innovation.

PMID- 25593207
TI  - Concise review: modeling multiple sclerosis with stem cell biological platforms:
      toward functional validation of cellular and molecular phenotypes in inflammation
      induced neurodegeneration.
AB  - In recent years, tremendous progress has been made in identifying novel
      mechanisms and new medications that regulate immune cell function in multiple
      sclerosis (MS). However, a significant unmet need is the identification of the
      mechanisms underlying neurodegeneration, because patients continue to manifest
      brain atrophy and disability despite current therapies. Neural and mesenchymal
      stem cells have received considerable attention as therapeutic candidates to
      ameliorate the disease in preclinical and phase I clinical trials. More recently,
      progress in somatic cell reprogramming and induced pluripotent stem cell
      technology has allowed the generation of human "diseased" neurons in a patient
      specific setting and has provided a unique biological tool that can be used to
      understand the cellular and molecular mechanisms of neurodegeneration. In the
      present review, we discuss the application and challenges of these technologies,
      including the generation of neurons, oligodendrocytes, and oligodendrocyte
      progenitor cells (OPCs) from patients and novel stem cell and OPC cellular
      arrays, in the discovery of new mechanistic insights and the future development
      of MS reparative therapies. 

PMID- 25593209
TI  - Giant epicardial cyst presenting as acute cardiac tamponade in a 2-year-old boy.
AB  - Cystic structures within the pericardial cavity are rare. They are divided into
      epicardial and pericardial variants. Pericardial and epicardial cysts rarely
      cause symptoms. This report describes a case of epicardial cyst with acute
      cardiac tamponade in a 2-year-old boy with no previous cardiac history who was
      transferred to our hospital because of hemodynamic instability. Emergency
      drainage of the pericardial effusion and complete excision of the cyst were
      performed through a median full sternotomy. 

PMID- 25593208
TI  - Defined culture of human embryonic stem cells and xeno-free derivation of retinal
      pigmented epithelial cells on a novel, synthetic substrate.
AB  - Age-related macular degeneration (AMD), a leading cause of blindness, is
      characterized by the death of the retinal pigmented epithelium (RPE), which is a
      monolayer posterior to the retina that supports the photoreceptors. Human
      embryonic stem cells (hESCs) can generate an unlimited source of RPE for cellular
      therapies, and clinical trials have been initiated. However, protocols for RPE
      derivation using defined conditions free of nonhuman derivatives (xeno-free) are
      preferred for clinical translation. This avoids exposing AMD patients to animal
      derived products, which could incite an immune response. In this study, we
      investigated the maintenance of hESCs and their differentiation into RPE using
      Synthemax II-SC, which is a novel, synthetic animal-derived component-free, RGD
      peptide-containing copolymer compliant with good manufacturing practices designed
      for xeno-free stem cell culture. Cells on Synthemax II-SC were compared with
      cultures grown with xenogeneic and xeno-free control substrates. This report
      demonstrates that Synthemax II-SC supports long-term culture of H9 and H14 hESC
      lines and permits efficient differentiation of hESCs into functional RPE.
      Expression of RPE-specific markers was assessed by flow cytometry, quantitative
      polymerase chain reaction, and immunocytochemistry, and RPE function was
      determined by phagocytosis of rod outer segments and secretion of pigment
      epithelium-derived factor. Both hESCs and hESC-RPE maintained normal karyotypes
      after long-term culture on Synthemax II-SC. Furthermore, RPE generated on
      Synthemax II-SC are functional when seeded onto parylene-C scaffolds designed for
      clinical use. These experiments suggest that Synthemax II-SC is a suitable,
      defined substrate for hESC culture and the xeno-free derivation of RPE for
      cellular therapies. 

PMID- 25593210
TI  - Obstructive Sleep Apnea and Atrial Fibrillation: Do They Synergistically Increase
      Cardiovascular Risk?

PMID- 25593211
TI  - Acute Kidney Injury in Elderly Patients With Non-ST Elevation Acute Coronary
      Syndrome: Insights From the Italian Elderly: ACS Study.
AB  - We examined the incidence and predictors of acute kidney injury (AKI) in elderly
      patients (>=75 years) enrolled in the prospective Italian Elderly acute coronary
      syndrome (ACS) study and explored the impact of AKI on clinical outcome. Acute
      kidney injury, defined according to the Acute Kidney Injury Network criteria,
      occurred in 128 (21%) of 615 patients. Patients submitted to coronary
      angiographic procedures did not present higher rate of AKI. The only baseline
      variables independently associated with AKI development were creatinine clearance
      (odds ratio [OR]: 0.98; 95% confidence interval [CI]: 0.97-0.99) and left
      ventricular ejection fraction (OR: 0.98; 95% CI: 0.96-0.99). Adverse clinical
      events were significantly higher in patients who developed AKI. After
      multivariable adjustment, AKI (hazard ratio: 2.73; 95% CI: 1.87-4.0) was an
      independent predictor of all-cause mortality within 1 year.

PMID- 25593212
TI  - Readability Assessment of Internet-Based Patient Education Materials Related to
      Parathyroid Surgery.
AB  - OBJECTIVES: Patient education is critical in obtaining informed consent and
      reducing preoperative anxiety. Written patient education material (PEM) can
      supplement verbal communication to improve understanding and satisfaction.
      Published guidelines recommend that health information be presented at or below a
      sixth-grade reading level to facilitate comprehension. We investigate the grade
      level of online PEMs regarding parathyroid surgery. METHODS: A popular internet
      search engine was used to identify PEM discussing parathyroid surgery. Four
      formulas were used to calculate readability scores: Flesch Reading Ease (FRE),
      Flesch-Kincaid Grade Level (FKGL), Gunning Frequency of Gobbledygook (GFOG), and
      Simple Measure of Gobbledygook (SMOG). RESULTS: Thirty web-based articles
      discussing parathyroid surgery were identified. The average FRE score was 42.8
      (+/-1 standard deviation [SD] 16.3; 95% confidence interval [CI], 36.6-48.8;
      range, 6.1-71.3). The average FKGL score was 11.7 (+/-1 SD 3.3; 95% CI, 10.5
      12.9; range, 6.1-19.0). The SMOG scores averaged 14.2 (+/-1 SD 2.6; 95% CI, 13.2
      15.2; range, 10.7-21.9), and the GFOG scores averaged 15.0 (+/-1 SD 3.5; 95% CI,
      13.7-16.3; range, 10.6-24.8). CONCLUSION: Online PEM on parathyroid surgery is
      written above the recommended sixth-grade reading level. Improving readability of
      PEM may promote better health education and compliance.

PMID- 25593213
TI  - Carbohydrate Intake, Glycemic Index, Glycemic Load, and Stroke: A Meta-analysis
      of Prospective Cohort Studies.
AB  - The objective of this study was to investigate associations between carbohydrate
      intake/glycemic index (GI)/glycemic load (GL) and stroke risk. A literature
      search of MEDLINE, Embase, Web of Science, and CBM databases was performed to
      retrieve eligible studies published up to March 2014. Pooled relative risks (RRs)
      with 95% confidence intervals (CIs) were used to evaluate the strength of this
      association. Publication bias was assessed by the Egger's regression asymmetry
      test and Begg's rank correlation test with Begg's funnel plot. All analyses were
      conducted using software STATA 12.0 (StataCorp LP, College Station, TX) and SAS
      version 9.1 (SAS Institute Inc, Cary, NC). We identified 7 prospective studies
      that met the inclusion criteria and processed data from cohort studies to update
      available evidence. There were 25 independent estimates and 225 000 participants
      free of diabetes from 6 different countries; 3046 stroke events were included;
      and the follow-up range was 5 to 18 years. High GI was not associated with risk
      of stroke events (pooled RR = 1.10; 95% CI: 0.99-1.21); GL was a risk factor for
      stroke (pooled RR = 1.19; 95% CI: 1.05-1.36). There was no significant
      association between high carbohydrate intake and stroke risk (RR = 1.12; 95% CI:
      0.93-1.35). A daily high GL diet is the risk factor of stroke event, and further
      researches need to verify the meta-analyses results and study associated
      mechanisms. 

PMID- 25593214
TI  - Identifying academic demands that occasion problem behaviors for students with
      behavioral disorders: illustrations at the elementary school level.
AB  - In two independent experiments, we (a) examined aspects of academic demands
      associated with the problem behaviors of two elementary students with behavioral
      disorders and (b) investigated the effects of academic interventions to decrease
      problem behaviors and increase task engagement. Preliminary functional behavior
      assessment data suggested each student participant's problem behaviors functioned
      to escape/avoid academic demands, and experimental structural analyses performed
      in naturalistic settings confirmed relations between their problem behaviors and
      specific features of academic tasks. Antecedent-based interventions were
      developed for each student and separate single-case alternating treatment
      experiments indicated functional relations between the academic interventions and
      appropriate task engagement. Findings support the use of structural analyses to
      inform academic planning and improve the behaviors of students who exhibit escape
      maintained problem behaviors associated with academic tasks. 

PMID- 25593215
TI  - Transition from paediatric to adult health services in Scotland for young people
      with cerebral palsy.
AB  - Transition from paediatric to adult health-care services has been characterized
      as being poorly planned and coordinated, resulting in a reduction in services and
      may be distressing for families. This study aimed to establish what provisions
      are currently available in Scotland for transition of young people with cerebral
      palsy and what some clinicians believe future provisions should involve. Semi
      structured interviews were conducted with 13 community paediatricians (or
      equivalents in health boards without community paediatricians) from 12 different
      Scottish health boards. Interviews were audio recorded, transcribed and analysed
      thematically using framework analysis. Both current transition provision and the
      areas that the clinicians felt needed improvement varied greatly between health
      boards. Key areas in need of improvement were coordination and communication
      within health services and also between health services and educational, social
      services and adult health services to which young people were transitioning.
      Transition remains problematic and variable. For transition to be improved,
      further research is needed to explore the effect this variation is having on
      young people and their families.

PMID- 25593216
TI  - Effects of cerebral ischemia on human neurovascular coupling, CO2 reactivity, and
      dynamic cerebral autoregulation.
AB  - Cerebral blood flow (CBF) regulation can be impaired in acute ischemic stroke but
      the combined effects of dynamic cerebral autoregulation (CA), CO2 cerebrovascular
      reactivity (CVR), and neurovascular coupling (NVC), obtained from simultaneous
      measurements, have not been described. CBF velocity in the middle cerebral artery
      (MCA) (CBFv, transcranial Doppler), blood pressure (BP, Finometer), and end-tidal
      Pco2 (PetCO2 , infrared capnography) were recorded during a 1-min passive
      movement of the arm in 27 healthy controls [mean age (SD) 61.4 (6.0) yr] and 27
      acute stroke patients [age 63 (11.7) yr]. A multivariate autoregressive-moving
      average model was used to separate the contributions of BP, arterial Pco2 (PaCO2
      ), and the neural activation to the CBFv responses. CBFv step responses for the
      BP, CO2, and stimulus inputs were also obtained. The contribution of the stimulus
      to the CBFv response was highly significant for the difference between the
      affected side [area under the curve (AUC) 104.5 (4.5)%] and controls [AUC 106.9
      (4.3)%; P = 0.008]. CBFv step responses to CO2 [affected hemisphere 0.39 (0.7),
      unaffected 0.55 (0.8), controls 1.39 (0.9)%/mmHg; P = 0.01, affected vs.
      controls; P = 0.025, unaffected vs. controls] and motor stimulus inputs [affected
      hemisphere 0.20 (0.1), unaffected 0.22 (0.2), controls 0.37 (0.2) arbitrary
      units; P = 0.009, affected vs. controls; P = 0.02, unaffected vs. controls] were
      reduced in the stroke group compared with controls. The CBFv step responses to
      the BP input at baseline and during the paradigm were not different between
      groups (P = 0.07), but PetCO2 was lower in the stroke group (P < 0.05). These
      results provide new insights into the interaction of CA, CVR, and NVC in both
      health and disease states. 

PMID- 25593217
TI  - Role of p38 MAPK pathway in 17beta-estradiol-mediated attenuation of hemorrhagic
      shock-induced hepatic injury.
AB  - Although 17beta-estradiol (E2) treatment following hemorrhagic shock or ischemic
      reperfusion prevents organs from dysfunction and injury, the precise mechanism
      remains unknown. We hypothesize that the E2-mediated attenuation of liver injury
      following hemorrhagic shock and fluid resuscitation occurs via the p38 mitogen
      activated protein kinase (MAPK)-dependent heme oxygenase (HO)-1 pathway. After a
      5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood
      pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of
      resuscitation, rats were treated with vehicle, E2 (1 mg/kg) alone, or E2 plus p38
      MAPK inhibitor SB-203580 (2 mg/kg), HO-1 inhibitor chromium mesoporphyrin-IX
      chloride (2.5 mg/kg) or estrogen receptor antagonist ICI 182,780 (3 mg/kg). At 2
      h after hemorrhagic shock and fluid resuscitation, the liver injury markers were
      significantly increased compared with sham-operated control. Hemorrhagic shock
      resulted in a significant decrease in p38 MAPK phosphorylation compared with the
      shams. Administration of E2 following hemorrhagic shock normalized liver p38 MAPK
      phosphorylation, further increased HO-1 expression, and reduced cleaved caspase-3
      levels. Coadministration of SB-203580 abolished the E2-mediated attenuation of
      the shock-induced liver injury markers. In addition, administration of chromium
      mesoporphyrin-IX chloride or ICI 182,780 abolished E2-mediated increases in liver
      HO-1 expression or p38 MAPK activation following hemorrhagic shock. Our results
      collectively suggest that the salutary effects of E2 on hepatic injury following
      hemorrhagic shock and resuscitation are in part mediated through an estrogen
      receptor-related p38 MAPK-dependent HO-1 upregulation. 

PMID- 25593218
TI  - Achilles tendon strain energy in distance running: consider the muscle energy
      cost.
AB  - The return of tendon strain energy is thought to contribute to reducing the
      energy cost of running (Erun). However, this may not be consistent with the
      notion that increased Achilles tendon (AT) stiffness is associated with a lower
      Erun. Therefore, the purpose of this study was to quantify the potential for AT
      strain energy return relative to Erun for male and female runners of different
      abilities. A total of 46 long distance runners [18 elite male (EM), 12 trained
      male (TM), and 16 trained female (TF)] participated in this study. Erun was
      determined by indirect calorimetry at 75, 85, and 95% of the speed at lactate
      threshold (sLT), and energy cost per stride at each speed was estimated from
      previously reported stride length (SL)-speed relationships. AT force during
      running was estimated from reported vertical ground reaction force (Fz)-speed
      relationships, assuming an AT:ground reaction force moment arm ratio of 1.5. AT
      elongation was quantified during a maximal voluntary isometric contraction using
      ultrasound. Muscle energy cost was conservatively estimated on the basis of AT
      force and estimated cross-bridge mechanics and energetics. Significant group
      differences existed in sLT (EM > TM > TF; P < 0.001). A significant group * speed
      interaction was found in the energy storage/release per stride (TM > TF > EM; P <
      0.001), the latter ranging from 10 to 70 J/stride. At all speeds and in all
      groups, estimated muscle energy cost exceeded energy return (P < 0.001). These
      results show that during distance running the muscle energy cost is substantially
      higher than the strain energy release from the AT. 

PMID- 25593219
TI  - Sulforaphane alleviates muscular dystrophy in mdx mice by activation of Nrf2.
AB  - Sulforaphane (SFN), one of the most important isothiocyanates in the human diet,
      is known to have chemo-preventive and antioxidant activities in different tissues
      via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated
      induction of antioxidant/phase II enzymes, such as heme oxygenase-1 and NAD(P)H
      quinone oxidoreductase 1. However, its effects on muscular dystrophy remain
      unknown. This work was undertaken to evaluate the effects of SFN on Duchenne
      muscular dystrophy. Four-week-old mdx mice were treated with SFN by gavage (2
      mg.kg body wt(-1).day(-1) for 8 wk), and our results demonstrated that SFN
      treatment increased the expression and activity of muscle phase II enzymes
      NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 with a Nrf2-dependent
      manner. SFN significantly increased skeletal muscle mass, muscle force (~30%),
      running distance (~20%), and GSH-to-GSSG ratio (~3.2-fold) of mdx mice and
      decreased the activities of plasma creatine phosphokinase (~45%) and lactate
      dehydrogenase (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy
      (~20%), and malondialdehyde levels (~60%). Furthermore, SFN treatment also
      reduced the central nucleation (~40%), fiber size variability, and inflammation
      and improved the sarcolemmal integrity of mdx mice. Collectively, these results
      show that SFN can improve muscle function and pathology and protect dystrophic
      muscle from oxidative damage in mdx mice associated with Nrf2 signaling pathway,
      which indicate Nrf2 may have clinical implications for the treatment of patients
      with muscular dystrophy. 

PMID- 25593220
TI  - Commentaries on Viewpoint: The ongoing need for good physiological investigation:
      Obstructive sleep apnea in HIV patients as a paradigm.

PMID- 25593222
TI  - Corrigendum.

PMID- 25593221
TI  - Last Word on Viewpoint: The ongoing need for good physiological investigation:
      Obstructive sleep apnea in HIV patients as a paradigm.

PMID- 25593223
TI  - Association between corrected QT interval and inflammatory cytokines in
      rheumatoid arthritis.
AB  - OBJECTIVE: Corrected QT (QTc) interval predicts all-cause and cardiovascular
      mortality and may contribute to the increased mortality risk in rheumatoid
      arthritis (RA). Animal experiments have shown that proinflammatory cytokines
      [tumor necrosis factor (TNF)-alpha and interleukin 1 (IL-1)] can prolong
      cardiomyocyte action potential. We sought to determine whether elevations in
      circulating inflammatory cytokines were independently associated with QTc
      prolongation in patients with RA. METHODS: One hundred twelve patients [median
      age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA
      cohort underwent baseline 12-lead electrocardiograms for QT interval measurement
      and contemporary blood sampling to assess concentrations of inflammatory markers
      including C-reactive protein (CRP), TNF-alpha, and interleukins (IL-1alpha, IL
      1beta, IL-6, IL-10). QTc was calculated using the Bazett (QTBAZ = QT / ?RR) and
      Framingham Heart Study (QTFHS = QT + 0.154 * [1 - RR]) heart rate correction
      formulas. RESULTS: Inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-10) were
      positively correlated with QTBAZ (Spearman rank correlation coefficient rho =
      0.199, 0.210, 0.222, 0.333; all p < 0.05). In multivariable regression analysis,
      these associations were all confounded by age except IL-10, where higher tertile
      groups were independently and positively associated with QTBAZ (beta = 0.202, p =
      0.023) and QTFHS (beta = 0.223, p = 0.009) when compared to the lower tertile.
      CRP (per unit increase) was independently associated with QTBAZ (beta = 0.278, p
      = 0.001), but not QTFHS. CONCLUSION: To our knowledge, ours is the first study
      demonstrating a contemporary link between inflammatory cytokines and QT interval
      in humans. Our results suggest that a lower inflammatory burden may protect
      against QTc prolongation in patients with RA. However, further studies are
      required to confirm the effects of pro- and antiinflammatory cytokines on QTc
      interval.

PMID- 25593224
TI  - Takayasu arteritis-associated pulmonary hypertension.
AB  - OBJECTIVE: To investigate the probable pathogenesis, clinical features,
      diagnosis, and therapy of patients with pulmonary hypertension (PH) in Takayasu
      arteritis (TA). METHODS: A total of 48 patients with TA who had PH, 20 patients
      with TA who had pulmonary arterial involvement (PA) without PH, and 30 patients
      with idiopathic pulmonary arterial hypertension (IPAH) were enrolled in the study
      from 2009 to 2013. RESULTS: Among the 48 patients with TA who had PH, 36 (75.0%)
      had PA, and left heart disease (LHD) was present in 12 (25.0%). Serum levels of
      big endothelin 1 (ET-1) were independently correlated with pulmonary arterial
      systolic pressure (r = 0.33, p = 0.04). Compared to patients with IPAH, patients
      with PH because of PA who underwent right heart catheterization had lower average
      cardiac indexes (2.0 +/- 0.5 vs 3.0 +/- 1.2 l/min/m(2), p = 0.05), and they all
      developed favorable responses to acute vasodilator testing (100%) in comparison
      to 10 of the patients with IPAH (33.3%). During a mean followup of 36.0 +/- 13.2
      months (12.0-65.0 mos), of the patients with PH associated with PA, 3 died of
      heart failure. Six patients who underwent pulmonary artery revascularization were
      found to have good prognoses after followup for a mean duration of 6.2 +/- 1.9
      months. Additionally, 12 patients with PH with LHD were followed for 38.4 +/-
      15.6 months (12.0-60.0 mos), and 1 patient died of heart failure during the
      followup period. CONCLUSION: Patients with TA are at increased risk for PH. Early
      screening of patients with TA with unexplained symptoms related to PH should be
      applied. PH-specific therapies or revascularization may be effective treatments
      in the early stages of patients with PA, PH, and severe pulmonary artery
      stenosis.

PMID- 25593225
TI  - Assessment of fatigue in rheumatoid arthritis: a psychometric comparison of
      single-item, multiitem, and multidimensional measures.
AB  - OBJECTIVE: To compare the psychometric functioning of multidimensional disease
      specific, multiitem generic, and single-item measures of fatigue in patients with
      rheumatoid arthritis (RA). METHODS: Confirmatory factor analysis (CFA) and
      longitudinal item response theory (IRT) modeling were used to evaluate the
      measurement structure and local reliability of the Bristol RA Fatigue Multi
      Dimensional Questionnaire (BRAF-MDQ), the Medical Outcomes Study Short Form-36
      (SF-36) vitality scale, and the BRAF Numerical Rating Scales (BRAF-NRS) in a
      sample of 588 patients with RA. RESULTS: A 1-factor CFA model yielded a similar
      fit to a 5-factor model with subscale-specific dimensions, and the items from the
      different instruments adequately fit the IRT model, suggesting essential
      unidimensionality in measurement. The SF-36 vitality scale outperformed the BRAF
      MDQ at lower levels of fatigue, but was less precise at moderate to higher levels
      of fatigue. At these levels of fatigue, the living, cognition, and emotion
      subscales of the BRAF-MDQ provide additional precision. The BRAF-NRS showed a
      limited measurement range with its highest precision centered on average levels
      of fatigue. CONCLUSION: The different instruments appear to access a common
      underlying domain of fatigue severity, but differ considerably in their
      measurement precision along the continuum. The SF-36 vitality scale can be used
      to measure fatigue severity in samples with relatively mild fatigue. For samples
      expected to have higher levels of fatigue, the multidimensional BRAF-MDQ appears
      to be a better choice. The BRAF-NRS are not recommended if precise assessment is
      required, for instance in longitudinal settings.

PMID- 25593226
TI  - Isolated hematuria and sterile pyuria may indicate systemic lupus erythematosus
      activity.
AB  - OBJECTIVE: To identify patients presenting with isolated hematuria and/or pyuria
      in the absence of other systemic lupus erythematosus (SLE) disease activity,
      describe their demographics, and determine whether they present with evidence of
      SLE flare in a period adjacent to the presentation. METHODS: We studied patients
      followed at the University of Toronto Lupus Clinic between 1970 and 2012. An
      episode of isolated hematuria (> 5 red blood cells per high power field) and/or
      pyuria (> 5 white blood cells per high power field) was defined as 2 consecutive
      visits with these findings in the absence of other concurrent SLE manifestations
      such as proteinuria, casts, or azotemia. We then excluded patients whose findings
      might be explained by urinary tract infections, menstruation, urolithiasis,
      and/or anticoagulation. Only patients presenting with no other SLE disease
      activity were included. RESULTS: Isolated hematuria and/or pyuria were identified
      in 49 patients, of whom 17 were excluded according to the criteria above, leaving
      32. Twenty-four patients had another renal manifestation 1 year before and/or
      after the occurrence; 27 had a non-renal manifestation 1 year before and/or after
      the occurrence; 3 patients had a biopsy in the same time frame, all with evidence
      of active lupus nephritis. Therefore the majority of patients with an occurrence
      of isolated hematuria and/or pyuria had evidence of renal or other non-renal SLE
      disease activity at a time adjacent to this presentation. CONCLUSION: Although
      not proven, our results suggest that these manifestations were associated with
      SLE activity, either before or after the episode, and therefore may represent a
      phase of active disease.

PMID- 25593228
TI  - Neurocognitive impairment in corticosteroid-naive patients with active systemic
      lupus erythematosus: a prospective study.
AB  - OBJECTIVE: Neurocognitive impairment (NCI) has been intensively studied in
      patients with systemic lupus erythematosus (SLE). However, those studies have
      mostly included patients who were treated with corticosteroids, which may itself
      induce NCI. We investigated NCI in corticosteroid-naive people with SLE who did
      not exhibit any overt neuropsychiatric manifestations. METHODS: Forty-three
      inpatients with SLE who had no current or past neuropsychiatric history
      participated in the study. Patients and 30 healthy control subjects with similar
      demographic characteristics were given a 1-h battery of neuropsychological tests.
      NCI was defined as scores at least 2 SD below the mean of the healthy control
      group on at least 2 of the 7 neurocognitive domains. Results of clinical,
      laboratory, and neurologic tests were compared regarding the presence of NCI.
      RESULTS: NCI was identified in 12 patients (27.9%) with SLE and in 2 control
      subjects (6.7%). Patients with SLE showed a significant impairment compared with
      controls on tasks assessing immediate recall, complex attention/executive
      function, and psychomotor speed. We identified psychomotor speed (Digit Symbol
      Substitution Test) as the factor that best differentiated the 2 groups. Further,
      we identified the score of the SLE Disease Activity Index 2000 as an independent
      risk factor for NCI in patients with SLE. CONCLUSION: We conclude that reduced
      psychomotor speed is an SLE-specific pattern of NCI. Verbal-memory deficits that
      have been reported in patients with SLE were not evident among patients who were
      corticosteroid-naive. Our results indicate that impaired psychomotor speed may be
      added to the symptoms of early SLE.

PMID- 25593229
TI  - High degree of nonadherence to disease-modifying antirheumatic drugs in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To test medication adherence using the Compliance-Questionnaire
      Rheumatology (CQR). METHODS: Invitation letter and CQR were sent to 240 patients
      with rheumatoid arthritis. Followup CQR was sent 3 months later. Adherence was
      evaluated using CQR 80% cutoff scores. RESULTS: Seventy-eight patients who were
      being treated with disease-modifying antirheumatic drugs provided full
      information on the CQR at both points in time. Eleven patients (14.1%) were
      classified as adherent based on taking compliance (TC), with only 3 patients
      (3.8%) adherent in regard to correct dosing (CD) [followup: 13 (16.7%) and 3
      (3.8%) for TC and CD, respectively]. Nonadherence was not related to disease
      activity or side effects. CONCLUSION: We demonstrated low adherence, suggesting
      differences between doctors' records and patients' practice of antirheumatic drug
      therapy.

PMID- 25593227
TI  - Elevation of serum immunoglobulin free light chains during the preclinical period
      of rheumatoid arthritis.
AB  - OBJECTIVE: Immunoglobulin free light chains (FLC) represent biomarkers of B cell
      activity in rheumatoid arthritis (RA) and are associated with all-cause mortality
      in the general population. Our objective was to evaluate the relationships of
      serum FLC to preclinical disease, RA characteristics, and mortality in RA
      compared to non-RA subjects. METHODS: A population-based study in Olmsted County,
      Minnesota, USA, was performed by crosslinking a large cohort in the general
      population having available serum FLC measurements with established RA incidence
      and prevalence cohorts. Serum kappa, lambda, and total FLC and their trends
      relative to RA incidence were compared between RA and non-RA subjects. Regression
      models were used to determine the associations between FLC, disease
      characteristics, and mortality, testing for differential effects of FLC on
      mortality in RA. RESULTS: Among 16,609 subjects, 270 fulfilled the criteria for
      RA at the time of FLC measurement. Mean total FLC were significantly higher in RA
      compared to non-RA subjects (4.2 vs 3.3 mg/dl, p < 0.001). FLC became elevated 3
      5 years before the clinical onset of RA and remained elevated during followup.
      Polyclonal FLC were found to predict higher mortality in persons with RA, though
      elevation to the highest decile had a relatively lower effect on mortality in RA
      compared to non-RA subjects. CONCLUSION: Elevation of serum FLC precedes the
      development of RA and may be useful in monitoring B cell activity and disease
      progression. FLC are associated with mortality among patients with RA as well as
      the general population.

PMID- 25593230
TI  - Rates of serious infections and malignancies among patients with rheumatoid
      arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.
AB  - OBJECTIVE: Because of the role of tumor necrosis factor (TNF) in host defense, it
      was hypothesized that its inhibition might lead to an increased risk of
      malignancies and infections. The objective of our study was to assess the
      incidence of serious infections leading to hospitalization and malignancies among
      patients with rheumatoid arthritis (RA) receiving either TNF inhibitor or
      rituximab (RTX) therapy. METHODS: The study population was identified from the
      National Register for Biologic Treatment in Finland and the hospital records of
      Central Finland Central Hospital for conventional disease-modifying antirheumatic
      drug (cDMARD) users. Data on infections and malignancies were acquired from
      national healthcare registers. A Poisson model was used to calculate the adjusted
      incidence rate ratios (aIRR) and was composed of age, sex, time from diagnosis,
      year of the beginning of the followup, rheumatoid factor status, Disease Activity
      Score at 28 joints, Health Assessment Questionnaire, prior malignancy, prior
      serious infection, prior biologic use, and time-updated use of methotrexate,
      sulfasalazine, hydroxychloroquine, and oral corticosteroids as confounders.
      RESULTS: In total, during the followup of 10,994 patient-years, 92 malignancies
      and 341 serious infections were included in the analyses. The aIRR of infections
      compared to cDMARD users were 1.2 (95% CI 0.63-2.3), 0.84 (95% CI 0.53-1.3), 0.98
      (95% CI 0.60-1.6), and 1.1 (95% CI 0.59-1.9) for the patients treated with
      infliximab (IFX), etanercept, adalimumab, and RTX, respectively. The crude rates
      of malignancies were highest among the users of cDMARD and RTX, and lowest among
      patients treated with IFX with no differences in aIRR. CONCLUSION: Our results
      provide some reassurance of the safety of biologic treatments in the treatment of
      RA.

PMID- 25593231
TI  - The role of innate immunity in osteoarthritis: when our first line of defense
      goes on the offensive.
AB  - Although osteoarthritis (OA) has existed since the dawn of humanity, its
      pathogenesis remains poorly understood. OA is no longer considered a "wear and
      tear" condition but rather one driven by proteases where chronic low-grade
      inflammation may play a role in perpetuating proteolytic activity. While multiple
      factors are likely active in this process, recent evidence has implicated the
      innate immune system, the older or more primitive part of the body's immune
      defense mechanisms. The roles of some of the components of the innate immune
      system have been tested in OA models in vivo including the roles of synovial
      macrophages and the complement system. This review is a selective overview of a
      large and evolving field. Insights into these mechanisms might inform our ability
      to identify patient subsets and give hope for the advent of novel OA therapies. 

PMID- 25593233
TI  - Longterm (52-week) results of a phase III randomized, controlled trial of
      apremilast in patients with psoriatic arthritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of apremilast, an oral
      phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic
      arthritis (PsA) despite prior treatment. METHODS: Patients were randomized to
      placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n =
      168). Patients whose swollen and tender joint counts had not improved by >= 20%
      at Week 16 were considered nonresponders and were required to be re-randomized
      (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to
      placebo, or continued their initial treatment of apremilast dose. At Week 24, all
      remaining patients treated with placebo were re-randomized to apremilast 20 mg
      BID or 30 mg BID. RESULTS: An American College of Rheumatology 20 (ACR20)
      response at Week 16 was attained by significantly more patients receiving
      apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than
      placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n
      = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and
      54.6% (71/130, 30 mg BID) of patients. Response was also maintained across
      secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis
      severity, and physical function. The nature, incidence, and severity of adverse
      events were comparable over the 24-week and 52-week periods. The most common
      adverse events, diarrhea and nausea, generally occurred early and were self
      limited. CONCLUSION: Continuous apremilast treatment resulted in sustained
      improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety
      profile and was generally well tolerated. CLINICAL TRIAL REGISTRATION:
      NCT01172938.

PMID- 25593234
TI  - Objective evaluation of physical functioning after tumor necrosis factor
      inhibitory therapy in patients with ankylosing spondylitis: a selection of 3
      feasible performance-based tests.
AB  - OBJECTIVE: (1) To select a limited number of performance-based tests that are
      reliable, show improvement in physical functioning after tumor necrosis factor
      inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS), and
      generate information equivalent to the full set of tests, and (2) are feasible
      for use in daily clinical practice. METHODS: Eight performance-based tests were
      evaluated. To eliminate redundant testing, the tests that showed adequate
      reliability, the highest standardized response mean (SRM), and the largest
      proportion of patients with an improved performance-based physical functioning
      were selected. The selected tests were combined into a new criterion for
      improvement in physical functioning (AS Performance-based Improvement; ASPI). The
      number and percentage of improved patients identified with the ASPI and
      identified with the full set of performance tests were compared. RESULTS:
      Reliability for all tests was adequate to excellent (ICC 0.73-0.96). The tests
      for bending, putting on socks, and getting up from the floor had the highest SRM
      (0.52-0.74) and showed the largest proportion of improved patients after TNFi
      therapy. The combination of these 3 tests was feasible in daily clinical practice
      and showed improved physical functioning after TNFi therapy in 67% of the
      patients. CONCLUSION: The 3 selected tests are recommended for use in daily
      practice because they generate information comparable to the full set. They are
      reliable and feasible, and the combination of these tests showed improved
      physical functioning after TNFi therapy in 67% of the patients. Evaluation of
      physical functioning might be improved by adding these tests to other AS outcome
      measures.

PMID- 25593232
TI  - Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis
      and are associated with its future diagnosis.
AB  - OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies could further
      elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical
      disease. We compared the diagnostic accuracy of anti-CarP antibodies for future
      RA to other RA-related antibodies in military personnel. METHODS: Stored pre-RA
      diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf
      serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide
      antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and
      RF isotypes [immunoglobulin M (IgM), IgG, and IgA]. Positivity for all antibodies
      was determined as >= 2 SD of log-transformed means from controls. Relationships
      between autoantibodies and future RA were assessed in prediagnosis serum for all
      RA cases compared to controls using sensitivity, specificity, and logistic
      regression. Differences in diagnostic accuracy between antibody combinations were
      assessed using comparisons of area under the curves (AUC). RESULTS: Anti-CarP-FCS
      was 26% sensitive and 95% specific for future RA, whereas anti-CarP-Fib was 16%
      sensitive and 95% specific for future RA. Anti-CarP-FCS positivity was associated
      with future RA, while anti-CarP-Fib trended toward association. The antibody
      combination of anti-CCP2 and/or >= 2 RF (RF-Neph and/or RF-isotypes) resulted in
      an AUC of 0.72 for future RA, where the AUC was 0.71 with the addition of anti
      CarP-FCS to this prior combination. CONCLUSION: Adding anti-CarP-FCS to antibody
      combinations did not improve AUC. However, anti-CarP-FCS was associated with
      future onset of RA, and was present in prediagnosis serum in ~10% of RA cases
      negative for anti-CCP2 but positive for RF.

PMID- 25593235
TI  - Chronic obstructive pulmonary disease is common in never-smoking patients with
      primary Sjogren syndrome.
AB  - OBJECTIVE: To assess the prevalence of chronic obstructive pulmonary disease
      (COPD) in patients with primary Sjogren syndrome (pSS) and to study the
      association of COPD with cigarette smoking, radiographic features, respiratory
      symptoms, disease activity, and laboratory inflammatory and serological features
      in patients with pSS. METHODS: Fifty-one consecutive patients with pSS (mean age
      60 yrs, range 29-82 yrs, 49 women) were assessed by pulmonary function tests
      (PFT). The PFT results were compared with previously studied population-based
      controls, standardizing results with regard to sex, age, height, weight, and
      cigarette smoking. In addition, patients with pSS were assessed by computed
      tomography of the chest, the European League Against Rheumatism Sjogren Syndrome
      Disease Activity Index and Patient Reported Index, the St. George's Respiratory
      Questionnaire (which evaluates respiratory symptoms), and by laboratory
      inflammatory and serological tests. RESULTS: Forty-one percent of all patients
      with pSS and 30% of the never-smoking patients with pSS fulfilled the Global
      Initiative for Chronic Obstructive Lung Disease criteria for COPD. Vital capacity
      (VC), forced expiratory volume in 1 s (FEV1), FEV1/VC ratio, and DLCO were
      significantly decreased while residual volume (RV) and the RV/total lung capacity
      ratio were significantly increased in patients with pSS. Moderate correlations
      between PFT results, symptoms, and disease activity were found. However,
      laboratory inflammatory and serological features were poorly associated with PFT
      results in patients with pSS. CONCLUSION: COPD was a common finding in patients
      with pSS, even among never-smoking patients. An obstructive pattern was the
      predominant PFT finding in patients with pSS, although a superimposed restrictive
      lung disease could not be excluded. The results suggest that the disease per se
      is involved in the development of COPD in pSS.

PMID- 25593236
TI  - Incidence of malignancy and the risk of lymphoma in Japanese patients with
      rheumatoid arthritis compared to the general population.
AB  - OBJECTIVE: Recent advances in the management of patients with rheumatoid
      arthritis (RA) increased the rates of disease remission and patient life
      expectancy, while malignancy has become a more common cause of death. Here, we
      report the incidence of malignancy in a nationwide survey of Japanese patients
      with RA compared to the general population, focusing on the risk of lymphoma,
      which often arises in patients with RA. METHODS: Data on the occurrence of
      malignancy were collected from patients registered in a nationwide Japanese
      cohort database, the National Database of Rheumatic Diseases by iR-net in Japan,
      from 2003 to 2012. To adjust for different population composition and to compare
      the incidence of malignancy with the general population, standardized incidence
      rates (SIR) were calculated. To identify risk factors for lymphoma, individual
      patient data were obtained for multivariate analysis for the year before lymphoma
      diagnosis. RESULTS: In 10 years, the cohort composed of 66,953 patient-years
      yielded 559 malignancies, most frequently lung cancer, followed by gastric
      cancer, breast cancer, and lymphoma. The overall incidence of malignancies in
      patients with RA was slightly lower than in the general population (SIR 0.89, 95%
      CI 0.82-0.97). However, lymphoma risk was significantly higher (SIR 3.43, 95% CI
      2.59-4.28), whereas risk of colon, rectal, or liver cancer was lower. Significant
      risk factors for lymphoma were the use of methotrexate or tacrolimus, and higher
      age. CONCLUSION: Patients with RA had no higher overall incidence of
      malignancies, but lymphoma was significantly more frequent than in the general
      population.

PMID- 25593237
TI  - A simplified baseline prediction model for joint damage progression in rheumatoid
      arthritis: a step toward personalized medicine.
AB  - OBJECTIVE: To compare the performance of an extended model and a simplified
      prognostic model for joint damage in rheumatoid arthritis (RA) based on 3
      baseline risk factors: anticyclic citrullinated peptide antibodies (anti-CCP),
      erosions, and acute-phase reaction. METHODS: Data were used from the Nijmegen
      early RA cohort. An extended model and a simplified baseline prediction model
      were developed to predict joint damage progression between 0 and 3 years. Joint
      damage progression was assessed using the Ratingen score. In the extended model,
      prediction factors were positivity for anti-CCP and/or rheumatoid factor, the
      level of erythrocyte sedimentation rate, and the quantity of erosions. The
      prediction score was calculated as the sum of the regression coefficients. In the
      simplified model, the prediction factors were dichotomized and the number of risk
      factors was counted. Performances of both models were compared using
      discrimination and calibration. The models were internally validated using
      bootstrapping. RESULTS: The extended model resulted in a prediction score between
      0 and 5.6 with an area under the receiver-operation characteristic (ROC) curve of
      0.77 (95% CI 0.72-0.81). The simplified model resulted in a prediction score
      between 0 and 3. This model had an area under the ROC curve of 0.75 (95% CI 0.70
      0.80). In internal validation, the 2 models showed reasonably well the agreement
      between observed and predicted probabilities for joint damage progression (Hosmer
      Lemeshow test p > 0.05 and calibration slope near 1.0). CONCLUSION: A simple
      prediction model for joint damage progression in early RA, by only counting the
      number of risk factors, has adequate performance. This facilitates the
      translation of the theoretical prognostic models to daily clinical practice.

PMID- 25593238
TI  - Effects of macitentan and its active metabolite on cultured human systemic
      sclerosis and control skin fibroblasts.
AB  - OBJECTIVE: To investigate the effects of the endothelin 1 (ET-1) receptor
      antagonists (ETRA) macitentan, its active metabolite ACT-132577, and bosentan on
      myofibroblast activation and extracellular matrix production induced by ET-1 in
      cultured systemic sclerosis (SSc) and control skin fibroblasts. METHODS:
      Fibroblasts were obtained from skin biopsies of 6 patients with SSc and 5 healthy
      subjects. Some cultured cells were untreated or treated with macitentan, ACT
      132577, or bosentan alone (10 MUM). Other cultured cells were treated with ET-1
      alone (100 nM) or with ETRA, and after 1 h, also with ET-1. After 48 h of
      treatment, myofibroblast activation was investigated to evaluate the alpha-smooth
      muscle actin (alpha-SMA) expression by immunofluorescence; type I collagen (COL
      1) and fibronectin (FN) were investigated by immunocytochemistry, Western
      blotting, and quantitative real-time PCR (qRT-PCR). Statistical analysis was
      performed by the nonparametric Mann-Whitney U test. RESULTS: In cultured SSc skin
      fibroblasts, only the treatment with macitentan significantly reduced the basal
      level of alpha-SMA expression (p = 0.03 vs untreated cells). Macitentan also
      significantly reduced the basal level of COL-1 synthesis, similarly to bosentan
      (p < 0.05 vs untreated cells). Macitentan or ACT-132577 antagonized the ability
      of ET-1 to further induce alpha-SMA expression (p = 0.03), COL-1, and FN
      synthesis (p = 0.03, p = 0.005); bosentan showed similar effects. These results
      obtained by immunofluorescence and immunocytochemistry were confirmed by Western
      blotting and qRT-PCR. The downregulatory effects exerted by ETRA were observed
      also in cultured human control skin fibroblasts. CONCLUSION: Macitentan and ACT
      132577 seem to downregulate in vitro the profibrotic myofibroblast phenotype
      induced by ET-1 in cultured human SSc skin fibroblasts.

PMID- 25593239
TI  - A preliminary study of acoustic radiation force impulse quantification for the
      assessment of skin in diffuse cutaneous systemic sclerosis.
AB  - OBJECTIVE: To investigate skin elasticity using acoustic radiation force impulse
      (ARFI) quantification in systemic sclerosis (SSc), and compare the modified
      Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of
      the skin. METHODS: Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age
      matched and sex-matched healthy controls were evaluated. The SWV and thickness of
      skin were measured at 17 sites corresponding to those assessed in the mRSS in
      each participant. The SWV measurements of skin were compared between patients
      with dcSSc and healthy controls. The correlations between the mRSS and the skin
      SWV and thickness were explored using Spearman's correlation. RESULTS: The SWV
      values were higher in patients with dcSSc compared with healthy controls at right
      hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum,
      and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of
      uninvolved skin were higher than those of controls (p < 0.001), and the SWV
      values increased with increasing skin scores except for skin score 3 (p < 0.05).
      The sum of the SWV values correlated with total clinical skin score (r = 0.841, p
      < 0.001), and the sum of the skin thickness correlated with total clinical skin
      score (r = 0.740, p = 0.002). CONCLUSION: ARFI quantification is feasible and
      reliable for assessing the skin involvement in dcSSc. ARFI quantification could
      identify early skin change that may precede palpable skin involvement, and may be
      a valuable adjunct to skin evaluation in patients with SSc.

PMID- 25593240
TI  - Quantitation of circumferential syndesmophyte height along the vertebral rim in
      ankylosing spondylitis using computed tomography.
AB  - OBJECTIVE: Using the 3-D imaging capability of computed tomography (CT), we
      developed an algorithm quantitating syndesmophyte height along the entire
      vertebral rim. We investigated its reliability and sensitivity to change,
      performed a 2-year longitudinal study, and compared it to CT measures of
      syndesmophyte volume. METHODS: We performed thoracolumbar spine CT scans on 33
      patients at baseline, Year 1, and Year 2, and computed syndesmophyte height in 4
      intervertebral disc spaces (IDS). Height was computed every 5 degrees  (72
      angular sectors) along the vertebral rim. These 72 measures were summed to form
      the circumferential height per IDS, and results from 4 IDS were summed to provide
      results per patient. To assess reliability, we compared results between 2 scans
      performed on the same day in 9 patients. Validity was assessed by associations
      with spinal flexibility. RESULTS: Coefficient of variation for circumferential
      syndesmophyte height was 0.893% per patient, indicating excellent reliability.
      Based on the Bland-Altman analysis, an increase in circumferential height of more
      than 3.44% per patient represented a change greater than measurement error. At
      years 1 and 2, mean (SD) circumferential syndesmophyte height increases were
      10.2% (11.7%) and 16.1% (14.0%), respectively. Sensitivity to change was 0.72 and
      0.87 at years 1 and 2, respectively. Circumferential syndesmophyte height
      correlated with the Schober test (r = -0.56, p = 0.0003) and lateral
      thoracolumbar flexion (r = -0.73, p < 0.0001). CONCLUSION: CT-based
      circumferential syndesmophyte height had excellent reliability and good
      sensitivity to change. It was more highly correlated with spine flexibility than
      syndesmophyte volume. The algorithm shows promise for longitudinal studies of
      syndesmophyte growth.

PMID- 25593241
TI  - Personalizing treatment targets in rheumatoid arthritis by using a simple
      prediction model.
AB  - OBJECTIVE: To develop a personalized treatment target approach in patients with
      rheumatoid arthritis (RA) based on baseline risk factors for joint damage
      progression in combination with disease activity over time. METHODS: Data were
      used from the Nijmegen early RA cohort. Presence or absence of anticyclic
      citrullinated peptide antibodies (anti-CCP), high erythrocyte sedimentation rate,
      and erosions were translated into 4 risk profiles: 0, 1, 2, and 3. Joint damage
      progression was assessed with the Ratingen score, and disease activity with the
      original Disease Activity Score (DAS) over 3 years. The probability for joint
      damage progression was calculated for each risk profile and each DAS category
      using logistic regression models. The probabilities were translated into
      personalized disease activity treatment targets. RESULTS: More risk factors at
      baseline as well as a higher DAS level resulted in a higher probability for joint
      damage progression in a dose-dependent way. Low DAS corresponded with a
      probability of 0.0, 0.08, 0.20, and 0.58 in patients with 0, 1, 2, and 3 risk
      factors, respectively. Moderate DAS corresponded with a probability of 0.06 in
      patients with 0 risk factors and 0.35 with 1 risk factor. High DAS resulted in a
      probability of 0.50 with no risk factors present at baseline. CONCLUSION:
      Presence of anti-CCP, acute-phase response, and erosions at baseline can be used
      to set individual treatment targets in RA. In patients without these risk
      factors, a moderate DAS as a target is sufficient, while for patients with all 3
      risk factors, a low DAS is not strict enough to limit the risk for joint damage.

PMID- 25593242
TI  - Safety and efficacy of rituximab in childhood-onset systemic lupus erythematosus
      and other rheumatic diseases.
AB  - OBJECTIVE: Rituximab (RTX) has been used to treat many pediatric autoimmune
      conditions. We investigated the safety and efficacy of RTX in a variety of
      pediatric autoimmune diseases, especially systemic lupus erythematosus (SLE).
      METHODS: Retrospective study of children treated with RTX. Effectiveness data was
      recorded for patients with at least 12 months of followup; safety data was
      recorded for all subjects. RESULTS: The study included 104 children; 50 had SLE.
      Improvements in corticosteroid dosage, physician's global assessment of disease
      activity, and SLE-associated markers of disease activity were seen. The incidence
      of hospitalized infections was similar to previous studies of patients with
      childhood-onset SLE. CONCLUSION: RTX can be safely administered to children and
      appears to contribute to decreased disease activity and steroid burden.

PMID- 25593244
TI  - Complete Genome Sequence of the Salmonella enterica Serovar Paratyphi A
      Bacteriophage LSPA1 Isolated in China.
AB  - The bacteriophage LSPA1 was isolated from hospital sewage (Kunming, China), and
      lytic activity was demonstrated against the Salmonella enterica serovar Paratyphi
      A CMCC50973 strain. This bacteriophage has a 41,880-bp double-stranded DNA
      (dsDNA) genome encoding 58 coding sequences (CDSs) and belongs to the family
      Siphoviridae. 

PMID- 25593243
TI  - Variation in rheumatoid hand and wrist surgery among medicare beneficiaries: a
      population-based cohort study.
AB  - OBJECTIVE: To examine the rate and variation in rheumatoid arthritis (RA)-related
      hand and wrist surgery among Medicare (elderly) beneficiaries in the United
      States, and to identify the patient and provider factors that influence surgical
      rates. METHODS: Using the 2006-2010 100% Medicare claims data of beneficiaries
      with RA diagnosis, we examined rates of rheumatoid hand and wrist arthroplasty,
      arthrodesis, and hand tendon reconstruction in the United States. We used
      multivariate logistic regression models to examine variation in receipt of
      surgery by patient and regional characteristics (density of providers, intensity
      of use of biologic disease-modifying antirheumatic drugs). RESULTS: Between 2006
      and 2010, the annual rate of RA-related hand and wrist arthroplasty or
      arthrodesis was 23.1 per 10,000 patients, and the annual rate of hand tendon
      reconstruction was 4.2 per 10,000 patients. The rates of surgery varied 9-fold
      across hospital referral regions in the United States. Younger patient age,
      female sex, white race, higher socioeconomic status (SES), and rural residence
      were associated with a higher likelihood of undergoing arthroplasty and
      arthrodesis. We observed a significant decline in rate of arthroplasty and
      arthrodesis with increasing density of rheumatologists. Tendon reconstruction was
      not influenced by provider factors, but was correlated with age, race, SES, and
      rural status of the patients. CONCLUSION: Surgical reconstruction of rheumatoid
      hand deformities varies widely across the United States, driven by both regional
      availability of subspecialty care in rheumatology and individual patient factors.

PMID- 25593245
TI  - Draft Genome Sequences of Four Closely Linked Vibrio vulnificus Isolates from the
      Biotype 1 Environmental Genotype.
AB  - Biotype 1 of Vibrio vulnificus, which causes severe invasive intestinal and wound
      infections, is split into two genotypes with all previously sequenced clinical
      isolates from the C genotypes. We report here the whole-genome sequencing of two
      clinical isolates and two closely linked oyster isolates from the E genotype for
      comparative studies. 

PMID- 25593246
TI  - Draft Genome Sequence of Sulfurospirillum sp. Strain MES, Reconstructed from the
      Metagenome of a Microbial Electrosynthesis System.
AB  - A draft genome of Sulfurospirillum sp. strain MES was isolated through taxonomic
      binning of a metagenome sequenced from a microbial electrosynthesis system (MES)
      actively producing acetate and hydrogen. The genome contains the nosZDFLY genes,
      which are involved in nitrous oxide reduction, suggesting the potential role of
      this strain in denitrification. 

PMID- 25593247
TI  - Draft Genome Sequence of the Quorum-Sensing and Biofilm-Producing Pseudomonas
      aeruginosa Strain Pae221, Belonging to the Epidemic High-Risk Clone Sequence Type
      274.
AB  - Pseudomonas aeruginosa Pae221 is a clinical isolate from blood culture. Pae221
      was found to be a strong quorum-sensing and biofilm-producing strain and also
      demonstrates a notable production of phenazines. This strain belongs to sequence
      type 274 (ST274), an epidemic high-risk clone. Here, we report the draft genome
      sequence of P. aeruginosa Pae221. 

PMID- 25593248
TI  - Genome Sequence of the Heteropolysaccharide-Producing Strain Lactobacillus
      mucosae DPC 6426.
AB  - Exopolysaccharide-synthesizing Lactobacillus mucosae DPC 6426 is a
      heterofermentative strain, which has demonstrated cholesterol-lowering properties
      in an animal model of lipid-driven atherosclerosis. The genome revealed a
      plethora of homologues linked to carbohydrate metabolism and mucin binding. 

PMID- 25593249
TI  - Draft Genome Sequence of Novosphingobium sp. Strain MBES04, Isolated from Sunken
      Wood from Suruga Bay, Japan.
AB  - This report describes the draft genome sequence of Novosphingobium sp. strain
      MBES04, isolated from sunken wood from Suruga Bay, Japan, which is capable of
      degrading a wide range of lignin-related aromatic monomers. The draft genome
      sequence contains 5,361,448 bp, with a G+C content of 65.4%. 

PMID- 25593250
TI  - Draft Genome Sequences of Klebsiella pneumoniae Clinical Type Strain ATCC 13883
      and Three Multidrug-Resistant Clinical Isolates.
AB  - Klebsiella pneumoniae is a Gram-negative human pathogen capable of causing
      hospital-acquired infections with an increasing risk to human health. The total
      DNA from four clinically relevant strains was sequenced to >100* coverage,
      providing high-quality genome assemblies for K. pneumoniae strains ATCC 13883,
      KP4640, 101488, and 101712. 

PMID- 25593251
TI  - Draft Genome Sequence of Shewanella sp. ECSMB14101, Isolated from the East China
      Sea.
AB  - Shewanella sp. ECSMB14101 was isolated from marine biofilms formed on the East
      China Sea. The draft genome sequence comprises 4,272,451 bp with a G+C content of
      49.82%. Information on this draft genome will contribute to the understanding of
      bacterium-animal interactions. 

PMID- 25593252
TI  - Draft Genome Sequence of the Cyanobacterium Aphanizomenon flos-aquae Strain
      2012/KM1/D3, Isolated from the Curonian Lagoon (Baltic Sea).
AB  - We report here the de novo genome assembly of a cyanobacterium, Aphanizomenon
      flos-aquae strain 2012/KM1/D3, a harmful bloom-forming species in temperate
      aquatic ecosystems. The genome is 5.7 Mb with a G+C content of 38.2%, and it is
      enriched mostly with genes involved in amino acid and carbohydrate metabolism. 

PMID- 25593253
TI  - Complete Genome Sequence of Pseudoalteromonas sp. Strain OCN003, Isolated from
      Kane'ohe Bay, O'ahu, Hawaii.
AB  - Pseudoalteromonas sp. strain OCN003 is a marine gammaproteobacterium that was
      isolated from a diseased colony of the common Hawaiian reef coral, Montipora
      capitata, found on a reef surrounding Moku o Lo'e in Kane'ohe Bay, Hawaii. Here,
      we report the complete genome of Pseudoalteromonas sp. strain OCN003. 

PMID- 25593254
TI  - Complete Genome Sequence of Listeria monocytogenes NTSN, a Serovar 4b and Animal
      Source Strain.
AB  - Listeria monocytogenes is an important foodborne pathogen that causes infections
      in humans and animals and has a high mortality rate. The complete genome sequence
      of L. monocytogenes strain NTSN, a highly virulent and serovar 4b strain isolated
      from the brains of sheep in Jiangsu Province, China, is presented here. 

PMID- 25593255
TI  - Complete Genome Sequence of the Strain of Lymantria dispar Multiple
      Nucleopolyhedrovirus Found in the Gypsy Moth Biopesticide Virin-ENSh.
AB  - We report the genome sequence of an alphabaculovirus from the gypsy moth
      (Lymantria dispar) biopesticide Virin-ENSh. The genome sequence is 161,712 bp,
      and its structure and sequence similarity indicate that the virus used in Virin
      ENSh is a strain of the species Lymantria dispar multiple nucleopolyhedrovirus. 

PMID- 25593256
TI  - Draft Genome Sequence of Thermus sp. Isolate 2.9, Obtained from a Hot Water
      Spring Located in Salta, Argentina.
AB  - Thermus sp. isolate 2.9 was obtained from a hot water spring in Salta, Argentina.
      Here, we report the draft genome sequence (2,485,434 bp) of this isolate, which
      consists of 11 scaffolds of >10 kbp and 2,719 protein-coding sequences. 

PMID- 25593258
TI  - Draft Genome Sequence of Halomonas hydrothermalis MTCC 5445, Isolated from the
      West Coast of India.
AB  - We announce here the draft genome sequence of Halomonas hydrothermalis MTCC 5445,
      a halophilic bacterium of the class Gammaproteobacteria. It was isolated from the
      sea coast of Aadri, Veraval, Gujarat, India. Its genome contains genes for
      polyhydroxybutyrate (PHB), a biodegradable polymer that can be used as a
      substitute for petroleum plastics. 

PMID- 25593257
TI  - Complete genome sequence of a newcastle disease virus isolate from an outbreak in
      central India.
AB  - The complete genome sequence of a Newcastle disease virus (NDV) strain
      NDV/Chicken/Nagpur/01/12 was isolated from vaccinated chicken farms in India
      during outbreaks in 2012. The genome is 15,192 nucleotides in length and is
      classified as genotype VII in class II. 

PMID- 25593259
TI  - Draft Genome Sequence of the Probiotic Strain Lactobacillus acidophilus ATCC
      4356.
AB  - We present the 1,956,699-bp draft genome sequence of Lactobacillus acidophilus
      strain ATCC 4356. Comparative genomic analysis revealed 99.96% similarity with L.
      acidophilus NCFM NC_006814.3 and 99.97% with La-14 NC_021181.2 genomes. 

PMID- 25593260
TI  - Draft Genome Sequence of Uncultivated Desulfosporosinus sp. Strain Tol-M,
      Obtained by Stable Isotope Probing Using [13C6]Toluene.
AB  - A draft Desulfosporosinus genome was assembled from the metagenome of a
      methanogenic [(13)C6]toluene-degrading community. The Desulfosporosinus sp.
      strain Tol-M genome is distinguished from that of previously published
      Desulfosporosinus strain by containing bss, bbs, and bam genes encoding enzymes
      for anaerobic biodegradation of monoaromatic hydrocarbons and lacking dsrAB genes
      for dissimilatory sulfate reduction. 

PMID- 25593261
TI  - Draft Genome Sequence of Uncultivated Toluene-Degrading Desulfobulbaceae
      Bacterium Tol-SR, Obtained by Stable Isotope Probing Using [13C6]Toluene.
AB  - The draft genome of a member of the bacterial family Desulfobulbaceae (phylum
      Deltaproteobacteria) was assembled from the metagenome of a sulfidogenic
      [(13)C6]toluene-degrading enrichment culture. The "Desulfobulbaceae bacterium Tol
      SR" genome is distinguished from related, previously sequenced genomes by suites
      of genes associated with anaerobic toluene metabolism, including bss, bbs, and
      bam. 

PMID- 25593262
TI  - Complete Genome Sequence of Bacillus megaterium Myophage Mater.
AB  - Bacillus megaterium is a ubiquitous, soil inhabiting Gram-positive bacterium that
      is a common model organism and is used in industrial applications for protein
      production. The following reports the complete sequencing and annotation of the
      genome of B. megaterium myophage Mater and describes the major features
      identified. 

PMID- 25593263
TI  - Complete Genome Sequence of Citrobacter freundii Myophage Miller.
AB  - Citrobacter freundii is a Gram-negative, opportunistic pathogen that can be fatal
      to newborns or immunocompromised patients. Bacteriophages against this bacterium
      can be useful for therapeutic purposes. Here, we describe the complete genome and
      the key features of the pseudo T-even C. freundii bacteriophage Miller. 

PMID- 25593264
TI  - Complete Genome Sequence of Bacillus megaterium Myophage Moonbeam.
AB  - Moonbeam is a newly isolated myophage of Bacillus megaterium, a common Gram
      positive bacterium that is routinely used for large-scale protein production.
      Bacteriophages have potential to be useful tools for industrial applications.
      Here, we describe the complete genome of Moonbeam and describe its features. 

PMID- 25593265
TI  - Draft Genome Sequence of Vibrio owensii GRA50-12, Isolated from Green Algae in
      the Intertidal Zone of Eastern Taiwan.
AB  - Vibrio owensii GRA50-12 was isolated from symbiotic green algae of coral. The
      genome contains genes encoding toxin production, virulence regulation, stress
      response proteins, types II, IV, and VI secretion systems, and proteins for the
      metabolism of aromatic compounds, which reflects its pathogenic potential and its
      ecological roles in the ocean. 

PMID- 25593266
TI  - Draft Genome Sequence of Robinsoniella peoriensis Strain WTD, Isolated from the
      Fecal Material of a Wood Turtle.
AB  - Here, we report the draft genome of Robinsoniella peoriensis strain WTD, which
      was isolated from the fecal material of a wood turtle. The genome size was
      7,391,415 bp with 41.1 mol% G+C. 

PMID- 25593267
TI  - Finished Genome Sequence of Bacillus cereus Strain 03BB87, a Clinical Isolate
      with B. anthracis Virulence Genes.
AB  - Bacillus cereus strain 03BB87, a blood culture isolate, originated in a 56-year
      old male muller operator with a fatal case of pneumonia in 2003. Here we present
      the finished genome sequence of that pathogen, including a 5.46-Mb chromosome and
      two plasmids (209 and 52 Kb, respectively). 

PMID- 25593268
TI  - Stoichiometry of transcription factors is critical for cardiac reprogramming.

PMID- 25593269
TI  - Exosomal microRNA clusters are important for the therapeutic effect of cardiac
      progenitor cells.

PMID- 25593270
TI  - Not growth but death: GM-CSF/IL-23 axis drives atherosclerotic plaque
      vulnerability by enhancing macrophage and DC apoptosis.

PMID- 25593271
TI  - Gone fission...: diverse consequences of cardiac Drp1 deficiency.

PMID- 25593272
TI  - Targeting microRNAs to limit myocardial lipid accumulation.

PMID- 25593273
TI  - A look at the bone marrow predicts the global outcome.

PMID- 25593274
TI  - Dawn of the Epi-LncRNAs: new path from Myheart.

PMID- 25593275
TI  - Inflammation and immunity in diseases of the arterial tree: players and layers.
AB  - The hypothesis that immunity and inflammation participate in the pathogenesis of
      vascular diseases has now gained widespread recognition and stimulated work
      around the globe. Broadening knowledge has extended the recognition of the role
      of immune and inflammatory mechanisms to all of the layers of the artery, to all
      levels of the arterial tree, and implicated virtually all arms, cellular players,
      and effector molecules and pathways involved in these crucial host defenses, that
      turn against us in disease. We provide here a guide to a compendium series of
      articles that aimed to look forward and broaden the traditional focus of
      immunopathogenesis of arterial disease, with the goal of integrating the players
      and the layers involved. Although the field has advanced remarkably, much remains
      to be done, and this commentary also aims to highlight some of the gaps that
      future research should strive to close on the participation of inflammation and
      immunity in arterial diseases. 

PMID- 25593276
TI  - Inflammatory and immune responses in the arterial media.
AB  - Inflammatory arterial diseases differentially affect the compartments of the
      vessel wall. The intima and adventitia are commonly involved by the disease
      process, with luminal and microvascular endothelial cells playing a critical role
      in the recruitment and activation of leukocytes. In contrast, the avascular media
      is often spared by immune-mediated disorders. Surprisingly, vascular smooth
      muscle cells (VSMCs), the predominant and often exclusive cell type of the media,
      are capable of robust proinflammatory responses to diverse stressors. The
      multiple cytokines and chemokines produced within the media can profoundly affect
      macrophage and T cell function, thus amplifying and shaping innate and adaptive
      immune responses. On the other hand, VSMCs and the extracellular matrix that they
      produce also display significant anti-inflammatory properties. The balance
      between the pro- and anti-inflammatory effects of VSMCs and their extracellular
      matrix versus the strength of the inciting immunologic events determines the
      pattern of medial pathology. Limitations on the extent of medial infiltration and
      injury, defined as medial immunoprivilege, are typically seen in arteriosclerotic
      diseases, such as atherosclerosis and transplant vasculopathy. Conversely,
      breakdown of medial immunoprivilege that manifests as more intense leukocytic
      infiltrates, loss of VSMCs, and destruction of the extracellular matrix
      architecture is a general feature of certain aneurysmal diseases and
      vasculitides. In this review, we consider the inflammatory and immune functions
      of VSMCs and how they may lead to medial immunoprivilege or medial inflammation
      in arterial diseases. 

PMID- 25593277
TI  - Danger signaling in atherosclerosis.
AB  - All aspects of the pathogenesis of atherosclerosis are critically influenced by
      the inflammatory response in vascular plaques. Research in the field of innate
      immunity from the past 2 decades has uncovered many novel mechanisms elucidating
      how immune cells sense microbes, tissue damage, and metabolic derangements. Here,
      we summarize which triggers of innate immunity appear during atherogenesis and by
      which pathways they can contribute to inflammation in atherosclerotic plaques.
      The increased understanding gained from studies assessing how immune activation
      is associated with the pathogenesis of atherosclerosis has provided many novel
      targets for potential therapeutic intervention. Excitingly, the concept that
      inflammation may be the core of cardiovascular disease is currently being
      clinically evaluated and will probably encourage further studies in this area. 

PMID- 25593279
TI  - Role of lymphocytes in myocardial injury, healing, and remodeling after
      myocardial infarction.
AB  - A large body of evidence produced during decades of research indicates that
      myocardial injury activates innate immunity. On the one hand, innate immunity
      both aggravates ischemic injury and impedes remodeling after myocardial
      infarction (MI). On the other hand, innate immunity activation contributes to
      myocardial healing, as exemplified by monocytes' central role in the formation of
      a stable scar and protection against intraventricular thrombi after acute
      infarction. Although innate leukocytes can recognize a wide array of self
      antigens via pattern recognition receptors, adaptive immunity activation requires
      highly specific cooperation between antigen-presenting cells and distinct antigen
      specific receptors on lymphocytes. We have only recently begun to examine
      lymphocyte activation's relationship to adaptive immunity and significance in the
      context of ischemic myocardial injury. There is some experimental evidence that
      CD4(+) T-cells contribute to ischemia-reperfusion injury. Several studies have
      shown that CD4(+) T-cells, especially CD4(+) T-regulatory cells, improve wound
      healing after MI, whereas depleting B-cells is beneficial post MI. That T-cell
      activation after MI is induced by T-cell receptor signaling implicates
      autoantigens that have not yet been identified in this context. Also, the
      significance of lymphocytes in humans post MI remains unclear, primarily as a
      result of methodology. This review summarizes current experimental evidence of
      lymphocytes' activation, functional role, and crosstalk with innate leukocytes in
      myocardial ischemia-reperfusion injury, wound healing, and remodeling after
      myocardial infarction. 

PMID- 25593278
TI  - Molecular regulation of cardiomyocyte differentiation.
AB  - The heart is the first organ to form during embryonic development. Given the
      complex nature of cardiac differentiation and morphogenesis, it is not surprising
      that some form of congenital heart disease is present in ~1 percent of newborns.
      The molecular determinants of heart development have received much attention over
      the past several decades. This has been driven in large part by an interest in
      understanding the causes of congenital heart disease coupled with the potential
      of using knowledge from developmental biology to generate functional cells and
      tissues that could be used for regenerative medicine purposes. In this review, we
      highlight the critical signaling pathways and transcription factor networks that
      regulate cardiomyocyte lineage specification in both in vivo and in vitro models.
      Special focus will be given to epigenetic regulators that drive the commitment of
      cardiomyogenic cells from nascent mesoderm and their differentiation into chamber
      specific myocytes, as well as regulation of myocardial trabeculation. 

PMID- 25593282
TI  - GLP-1 and exendin-4: not simply two of a kind.

PMID- 25593281
TI  - Macrophage sortilin promotes LDL uptake, foam cell formation, and
      atherosclerosis.
AB  - RATIONALE: Noncoding gene variants at the SORT1 locus are strongly associated
      with low-density lipoprotein cholesterol (LDL-C) levels, as well as with coronary
      artery disease. SORT1 encodes a protein called sortilin, and hepatic sortilin
      modulates LDL metabolism by targeting apolipoprotein B-containing lipoproteins to
      the lysosome. Sortilin is also expressed in macrophages, but its role in
      macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C
      levels is unknown. OBJECTIVE: To determine the effect of macrophage sortilin
      expression on LDL uptake, foam cell formation, and atherosclerosis. METHODS AND
      RESULTS: We crossed Sort1(-/-) mice onto a humanized Apobec1(-/-); hAPOB
      transgenic background and determined that Sort1 deficiency on this background had
      no effect on plasma LDL-C levels but dramatically reduced atherosclerosis in the
      aorta and aortic root. To test whether this effect was a result of macrophage
      sortilin deficiency, we transplanted Sort1(-/-);LDLR(-/-) or Sort1(+/+);LDLR(-/-)
      bone marrow into Ldlr(-/-) mice and observed a similar reduction in
      atherosclerosis in mice lacking hematopoetic sortilin without an effect on plasma
      LDL-C levels. In an effort to determine the mechanism by which hematopoetic
      sortilin deficiency reduced atherosclerosis, we found no effect of sortilin
      deficiency on macrophage recruitment or lipopolysaccharide-induced cytokine
      release in vivo. In contrast, sortilin-deficient macrophages had significantly
      reduced uptake of native LDL ex vivo and reduced foam cell formation in vivo,
      whereas sortilin overexpression in macrophages resulted in increased LDL uptake
      and foam cell formation. CONCLUSIONS: Macrophage sortilin deficiency protects
      against atherosclerosis by reducing macrophage uptake of LDL. Sortilin-mediated
      uptake of native LDL into macrophages may be an important mechanism of foam cell
      formation and contributor to atherosclerosis development.

PMID- 25593280
TI  - Fcgamma receptors and ligands and cardiovascular disease.
AB  - Fcgamma receptors (FcgammaRs) classically modulate intracellular signaling on
      binding of the Fc region of IgG in immune response cells. How FcgammaR and their
      ligands affect cardiovascular health and disease has been interrogated recently
      in both preclinical and clinical studies. The stimulation of activating FcgammaR
      in endothelial cells, vascular smooth muscle cells, and monocytes/macrophages
      causes a variety of cellular responses that may contribute to vascular disease
      pathogenesis. Stimulation of the lone inhibitory FgammacR, FcgammaRIIB, also has
      adverse consequences in endothelial cells, antagonizing NO production and
      reparative mechanisms. In preclinical disease models, activating FcgammaRs
      promote atherosclerosis, whereas FcgammaRIIB is protective, and activating
      FcgammaRs also enhance thrombotic and nonthrombotic vascular occlusion. The
      FcgammaR ligand C-reactive protein (CRP) has undergone intense study. Although in
      rodents CRP does not affect atherosclerosis, it causes hypertension and insulin
      resistance and worsens myocardial infarction. Massive data have accumulated
      indicating an association between increases in circulating CRP and coronary heart
      disease in humans. However, Mendelian randomization studies reveal that CRP is
      not likely a disease mediator. CRP genetics and hypertension warrant further
      investigation. To date, studies of genetic variants of activating FcgammaRs are
      insufficient to implicate the receptors in coronary heart disease pathogenesis in
      humans. However, a link between FcgammaRIIB and human hypertension may be
      emerging. Further knowledge of the vascular biology of FcgammaR and their ligands
      will potentially enhance our understanding of cardiovascular disorders,
      particularly in patients whose greater predisposition for disease is not
      explained by traditional risk factors, such as individuals with autoimmune
      disorders. 

PMID- 25593283
TI  - The beneficial effects of exercise on cartilage are lost in mice with reduced
      levels of ECSOD in tissues.
AB  - Osteoarthritis (OA) is associated with increased mechanical damage to joint
      cartilage. We have previously found that extracellular superoxide dismutase
      (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage
      may play a role in OA. We explored the effect of forced running as a surrogate
      for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding.
      Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129
      SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45
      min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint
      tissue was obtained for histology, immunohistochemistry, and protein analysis.
      Sedentary Het and WT mice were maintained for comparison. Whole tibias were
      studied for bone morphometry, finite element analysis, and mechanical testing.
      Forced running improved joint histology in WT mice. However, when ECSOD levels
      were reduced, this beneficial effect with running was lost. Het ECSOD runner mice
      had significantly worse histology scores compared with WT runner mice. Runner
      mice for both strains had increased bone strength in response to the running
      protocol, while Het mice showed evidence of a less robust bone structure in both
      runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint
      damage when joints were stressed by forced running. The bone tissues responded to
      increased loading with hypertrophy, regardless of mouse strain. We conclude that
      ECSOD plays an important role in protecting cartilage from damage caused by
      mechanical loading. 

PMID- 25593284
TI  - Acute and chronic effects of sprint interval exercise on postprandial lipemia in
      women at-risk for the metabolic syndrome.
AB  - Individuals diagnosed with the metabolic syndrome (MetS) exhibit elevated
      postprandial lipemia (PPL). The aims of this investigation were to determine 1)
      if an acute bout of sprint interval training (SIT) attenuates PPL; and 2) if the
      attenuation of PPL following 6 wk of SIT is magnified compared with a single
      session of SIT prior to training in women at-risk for MetS (n = 45; 30-65 yr).
      Women were randomized to SIT (n = 22) or a nonexercise control (n = 23; CON) for
      6 wk. Postprandial responses to a high-fat meal challenge (HFMC) were assessed in
      the CON group before (B-HFMC) and after (Post-HFMC) without prior exercise and in
      the SIT group at baseline (B-HFMC) without prior exercise, after an acute bout of
      SIT (four 30-s all-out sprints with 4-min recovery) prior to (Pre-HFMC), and
      after the 6-wk intervention (Post-HFMC). Responses to the HFMC were assessed by
      collecting venous blood samples in the fasted state and at 0, 30, 60, 120, and
      180 min postprandial. Compared with baseline, an acute bout of SIT before (Pre
      HFMC) and after the 6-wk intervention (Post-HFMC) significantly attenuated fasted
      TG (P < 0.05; 16.6% and 12.3%, respectively) and postprandial area under the
      curve (13.1% and 9.7%, respectively; tAUC) TG responses. There was no difference
      in fasted or tAUC TG responses between Pre-HFMC and Post-HFMC. SIT is an
      effective mode of exercise to reduce fasted and postprandial TG concentrations in
      women at-risk for MetS. Six weeks of SIT does not magnify the attenuation of PPL
      in response to a single session of SIT. 

PMID- 25593285
TI  - A method for assessing heterogeneity of blood flow and metabolism in exercising
      normal human muscle by near-infrared spectroscopy.
AB  - Heterogeneity in the distribution of both blood flow (Q) and O2 consumption (VO2)
      has not been assessed by near-infrared spectroscopy in exercising normal human
      muscle. We used near-infrared spectroscopy to measure the regional distribution
      of Q and VO2 in six trained cyclists at rest and during constant-load exercise
      (unloaded pedaling, 20%, 50%, and 80% of peak Watts) in both normoxia and hypoxia
      (inspired O2 fraction = 0.12). Over six optodes over the upper, middle, and lower
      vastus lateralis, we recorded 1) indocyanine green dye inflow after intravenous
      injection to measure Q; and 2) fractional tissue O2 saturation (StiO2) to
      estimate local VO2-to-Q ratios (Vo2/Q). Varying both exercise intensity and
      inspired O2 fraction provided a (directly measured) femoral venous O2 saturation
      range from about 10 to 70%, and a correspondingly wide range in StiO2. Mean Q
      weighted StiO2 over the six optodes related linearly to femoral venous O2
      saturation in each subject. We used this relationship to compute local muscle
      venous blood O2 saturation from StiO2 recorded at each optode, from which local
      VO2/Q could be calculated by the Fick principle. Multiplying regional VO2/Q by Q
      yielded the corresponding local VO2. While six optodes along only in one muscle
      may not fully capture the extent of heterogeneity, relative dispersion of both Q
      and VO2 was ~0.4 under all conditions, while that for VO2/Q was minimal (only
      ~0.1), indicating in fit young subjects 1) a strong capacity to regulate Q
      according to regional metabolic need; and 2) a likely minimal impact of
      heterogeneity on muscle O2 availability.

PMID- 25593286
TI  - Elevation in blood flow and shear rate prevents hyperglycemia-induced endothelial
      dysfunction in healthy subjects and those with type 2 diabetes.
AB  - Hyperglycemia, commonly present after a meal, causes transient impairment in
      endothelial function. We examined whether increases in blood flow (BF) protect
      against the hyperglycemia-mediated decrease in endothelial function in healthy
      subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects
      and 10 age- and sex-matched patients with T2DM underwent simultaneous bilateral
      assessment of brachial artery endothelial function by means of flow-mediated
      dilation (FMD) using high-resolution echo-Doppler. FMD was examined before and
      60, 120, and 150 min after a 75-g oral glucose challenge. We unilaterally
      manipulated BF by heating one arm between minute 30 and minute 60. Oral glucose
      administration caused a statistically significant, transient increase in blood
      glucose in both groups (P < 0.001). Forearm skin temperature, brachial artery BF,
      and shear rate significantly increased in the heated arm (P < 0.001), and to a
      greater extent compared with the nonheated arm in both groups (interaction effect
      P < 0.001). The glucose load caused a transient decrease in FMD% (P < 0.05),
      whereas heating significantly prevented the decline (interaction effect P <
      0.01). Also, when correcting for changes in diameter and shear rate, we found
      that the hyperglycemia-induced decrease in FMD can be prevented by local heating
      (P < 0.05). These effects on FMD were observed in both groups. Our data indicate
      that nonmetabolically driven elevation in BF and shear rate can similarly prevent
      the hyperglycemia-induced decline in conduit artery endothelial function in
      healthy volunteers and in patients with type 2 diabetes. Additional research is
      warranted to confirm that other interventions that increase BF and shear rate
      equally protect the endothelium when challenged by hyperglycemia. 

PMID- 25593288
TI  - Modeling the contribution of individual proteins to mixed skeletal muscle protein
      synthetic rates over increasing periods of label incorporation.
AB  - Advances in stable isotope approaches, primarily the use of deuterium oxide
      ((2)H2O), allow for long-term measurements of protein synthesis, as well as the
      contribution of individual proteins to tissue measured protein synthesis rates.
      Here, we determined the influence of individual protein synthetic rates,
      individual protein content, and time of isotopic labeling on the measured
      synthesis rate of skeletal muscle proteins. To this end, we developed a
      mathematical model, applied the model to an established data set collected in
      vivo, and, to experimentally test the impact of different isotopic labeling
      periods, used (2)H2O to measure protein synthesis in cultured myotubes over
      periods of 2, 4, and 7 days. We first demonstrated the influence of both relative
      protein content and individual protein synthesis rates on measured synthesis
      rates over time. When expanded to include 286 individual proteins, the model
      closely approximated protein synthetic rates measured in vivo. The model revealed
      a 29% difference in measured synthesis rates from the slowest period of
      measurement (20 min) to the longest period of measurement (6 wk). In support of
      these findings, culturing of C2C12 myotubes with isotopic labeling periods of 2,
      4, or 7 days revealed up to a doubling of the measured synthesis rate in the
      shorter labeling period compared with the longer period of labeling. From our
      model, we conclude that a 4-wk period of labeling is ideal for considering all
      proteins in a mixed-tissue fraction, while minimizing the slowing effect of fully
      turned-over proteins. In addition, we advocate that careful consideration must be
      paid to the period of isotopic labeling when comparing mixed protein synthetic
      rates between studies. 

PMID- 25593287
TI  - Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and
      mechanical properties in mice.
AB  - Conditions during spaceflight, such as the loss of the head-to-foot gravity
      vector, are thought to potentially alter cerebral blood flow and vascular
      resistance. The purpose of the present study was to determine the effects of long
      term spaceflight on the functional, mechanical, and structural properties of
      cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1
      biosatellite. Basilar arteries isolated from spaceflight (SF) (n = 6), habitat
      control (HC) (n = 6), and vivarium control (VC) (n = 16) mice were used for in
      vitro functional and mechanical testing and histological structural analysis. The
      results demonstrate that vasoconstriction elicited through a voltage-gated Ca(2+)
      mechanism (30-80 mM KCl) and thromboxane A2 receptors (10(-8) - 3 * 10(-5) M
      U46619) are lower in cerebral arteries from SF mice. Inhibition of Rho-kinase
      activity (1 MUM Y27632) abolished group differences in U46619-evoked
      contractions. Endothelium-dependent vasodilation elicited by acetylcholine (10
      MUM, 2 MUM U46619 preconstriction) was virtually absent in cerebral arteries from
      SF mice. The pressure-diameter relation was lower in arteries from SF mice
      relative to that in HC mice, which was not related to differences in the
      extracellular matrix protein elastin or collagen content or the elastin/collagen
      ratio in the basilar arteries. Diameter, medial wall thickness, and medial cross
      sectional area of unpressurized basilar arteries were not different among groups.
      These results suggest that the microgravity-induced attenuation of both
      vasoconstrictor and vasodilator properties may limit the range of vascular
      control of cerebral perfusion or impair the distribution of brain blood flow
      during periods of stress. 

PMID- 25593289
TI  - Automatic identification of physical activity types and sedentary behaviors from
      triaxial accelerometer: laboratory-based calibrations are not enough.
AB  - "Objective" methods to monitor physical activity and sedentary patterns in free
      living conditions are necessary to further our understanding of their impacts on
      health. In recent years, many software solutions capable of automatically
      identifying activity types from portable accelerometry data have been developed,
      with promising results in controlled conditions, but virtually no reports on
      field tests. An automatic classification algorithm initially developed using
      laboratory-acquired data (59 subjects engaging in a set of 24 standardized
      activities) to discriminate between 8 activity classes (lying, slouching,
      sitting, standing, walking, running, and cycling) was applied to data collected
      in the field. Twenty volunteers equipped with a hip-worn triaxial accelerometer
      performed at their own pace an activity set that included, among others,
      activities such as walking the streets, running, cycling, and taking the bus.
      Performances of the laboratory-calibrated classification algorithm were compared
      with those of an alternative version of the same model including field-collected
      data in the learning set. Despite good results in laboratory conditions, the
      performances of the laboratory-calibrated algorithm (assessed by confusion
      matrices) decreased for several activities when applied to free-living data.
      Recalibrating the algorithm with data closer to real-life conditions and from an
      independent group of subjects proved useful, especially for the detection of
      sedentary behaviors while in transports, thereby improving the detection of
      overall sitting (sensitivity: laboratory model = 24.9%; recalibrated model =
      95.7%). Automatic identification methods should be developed using data acquired
      in free-living conditions rather than data from standardized laboratory activity
      sets only, and their limits carefully tested before they are used in field
      studies. 

PMID- 25593290
TI  - Endothelial-to-mesenchymal transition in pulmonary hypertension.
AB  - BACKGROUND: The vascular remodeling responsible for pulmonary arterial
      hypertension (PAH) involves predominantly the accumulation of alpha-smooth muscle
      actin-expressing mesenchymal-like cells in obstructive pulmonary vascular
      lesions. Endothelial-to-mesenchymal transition (EndoMT) may be a source of those
      alpha-smooth muscle actin-expressing cells. METHODS AND RESULTS: In situ evidence
      of EndoMT in human PAH was obtained by using confocal microscopy of multiple
      fluorescent stainings at the arterial level, and by using transmission electron
      microscopy and correlative light and electron microscopy at the ultrastructural
      level. Findings were confirmed by in vitro analyses of human PAH and control
      cultured pulmonary artery endothelial cells. In addition, the mRNA and protein
      signature of EndoMT was recognized at the arterial and lung level by quantitative
      real-time polymerase chain reaction and Western blot analyses. We confirmed our
      human observations in established animal models of pulmonary hypertension
      (monocrotaline and SuHx). After establishing the first genetically modified rat
      model linked to BMPR2 mutations (BMPR2(Delta140Ex1/+) rats), we demonstrated that
      EndoMT is linked to alterations in signaling of BMPR2, a gene that is mutated in
      70% of cases of familial PAH and in 10% to 40% of cases of idiopathic PAH. We
      identified molecular actors of this pathological transition, including twist
      overexpression and vimentin phosphorylation. We demonstrated that rapamycin
      partially reversed the protein expression patterns of EndoMT, improved
      experimental PAH, and decreased the migration of human pulmonary artery
      endothelial cells, providing the proof of concept that EndoMT is druggable.
      CONCLUSIONS: EndoMT is linked to alterations in BPMR2 signaling and is involved
      in the occlusive vas cular remodeling of PAH, findings that may have therapeutic
      implications.

PMID- 25593291
TI  - Handling alters aggression and "loser" effect formation in Drosophila
      melanogaster.
AB  - In Drosophila, prior fighting experience influences the outcome of later
      contests: losing a fight increases the probability of losing second contests,
      thereby revealing "loser" effects that involve learning and memory. In these
      experiments, to generate and quantify the behavioral changes observed as
      consequences of losing fights, we developed a new behavioral arena that
      eliminates handling. We compared two commonly used fly handling procedures with
      this new chamber and demonstrated that handling influences aggressive behavior
      and prevents "loser" effect formation. In addition, we induced and observed novel
      aspects of learning associated with aggression such as the formation of robust
      winner effects. 

PMID- 25593292
TI  - Regionally selective requirement for D1/D5 dopaminergic neurotransmission in the
      medial prefrontal cortex in object-in-place associative recognition memory.
AB  - Object-in-place (OiP) memory is critical for remembering the location in which an
      object was last encountered and depends conjointly on the medial prefrontal
      cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine
      D1/D5 receptor neurotransmission within these brain regions for OiP memory.
      Bilateral infusion of D1/D5 receptor antagonists SCH23390 or SKF83566 into the
      medial prefrontal cortex, prior to memory acquisition, impaired OiP performance
      following a 5 min or 1 h delay. Retrieval was unaffected. Intraperirhinal or
      intrahippocampal infusions of SCH23390 had no effect. These results reveal a
      selective role for D1/D5 receptors in the mPFC during OiP memory encoding. 

PMID- 25593293
TI  - Epac activation initiates associative odor preference memories in the rat pup.
AB  - Here we examine the role of the exchange protein directly activated by cAMP
      (Epac) in beta-adrenergic-dependent associative odor preference learning in rat
      pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with
      odor, initiated preference learning, which was selective for the paired odor.
      Interestingly, pairing odor with Epac activation produced both short-term (STM)
      and long-term (LTM) odor preference memories. Training using beta-adrenergic
      activation paired with odor recruited rapid and transient ERK phosphorylation
      consistent with a role for Epac activation in normal learning. An ERK antagonist
      prevented intermediate-term memory (ITM) and LTM, but not STM. Epac agonist
      infusions induced ERK phosphorylation in the mitral cell layer, in the inner half
      of the dendritic external plexiform layer, in the glomeruli and, patchily, among
      granule cells. Increased CREB phosphorylation in the mitral and granule cell
      layers was also seen. Simultaneous blockade of both ERK and CREB pathways
      prevented any long-term beta-adrenergic activated odor preference memory, while
      LTM deficits associated with blocking only one pathway were prevented by stronger
      beta-adrenergic activation. These results suggest that Epac and PKA play parallel
      and independent, as well as likely synergistic, roles in creating cAMP-dependent
      associative memory in rat pups. They further implicate a novel ERK-independent
      pathway in the mediation of STM by Epac. 

PMID- 25593294
TI  - Hippocampus, perirhinal cortex, and complex visual discriminations in rats and
      humans.
AB  - Structures in the medial temporal lobe, including the hippocampus and perirhinal
      cortex, are known to be essential for the formation of long-term memory. Recent
      animal and human studies have investigated whether perirhinal cortex might also
      be important for visual perception. In our study, using a simultaneous oddity
      discrimination task, rats with perirhinal lesions were impaired and did not
      exhibit the normal preference for exploring the odd object. Notably, rats with
      hippocampal lesions exhibited the same impairment. Thus, the deficit is unlikely
      to illuminate functions attributed specifically to perirhinal cortex. Both lesion
      groups were able to acquire visual discriminations involving the same objects
      used in the oddity task. Patients with hippocampal damage or larger medial
      temporal lobe lesions were intact in a similar oddity task that allowed
      participants to explore objects quickly using eye movements. We suggest that
      humans were able to rely on an intact working memory capacity to perform this
      task, whereas rats (who moved slowly among the objects) needed to rely on long
      term memory. 

PMID- 25593295
TI  - The amygdala is critical for trace, delay, and contextual fear conditioning.
AB  - Numerous investigations have definitively shown amygdalar involvement in delay
      and contextual fear conditioning. However, much less is known about amygdala
      contributions to trace fear conditioning, and what little evidence exists is
      conflicting as noted in previous studies. This discrepancy may result from
      selective targeting of individual nuclei within the amygdala. The present
      experiments further examine the contributions of amygdalar subnuclei to trace,
      delay, and contextual fear conditioning. Rats were trained using a 10-trial
      trace, delay, or unpaired fear conditioning procedure. Pretraining lesions
      targeting the entire basolateral amygdala (BLA) resulted in a deficit in trace,
      delay, and contextual fear conditioning. Immediate post-training infusions of the
      protein synthesis inhibitor, cycloheximide, targeting the basal nucleus of the
      amygdala (BA) attenuated trace and contextual fear memory expression, but had no
      effect on delay fear conditioning. However, infusions targeting the lateral
      nucleus of the amygdala (LA) immediately following conditioning attenuated
      contextual fear memory expression, but had no effect on delay or trace fear
      conditioning. In follow-up experiments, rats were trained using a three-trial
      delay conditioning procedure. Immediate post-training infusions targeting the LA
      produced deficits in both delay tone and context fear, while infusions targeting
      the BA produced deficits in context but not delay tone fear. These data fully
      support a role for the BLA in trace, delay, and contextual fear memories.
      Specifically, these data suggest that the BA may be more critical for trace fear
      conditioning, whereas the LA may be more critical for delay fear memories. 

PMID- 25593296
TI  - Effects of long-term representations on free recall of unrelated words.
AB  - Human memory stores vast amounts of information. Yet recalling this information
      is often challenging when specific cues are lacking. Here we consider an
      associative model of retrieval where each recalled item triggers the recall of
      the next item based on the similarity between their long-term neuronal
      representations. The model predicts that different items stored in memory have
      different probability to be recalled depending on the size of their
      representation. Moreover, items with high recall probability tend to be recalled
      earlier and suppress other items. We performed an analysis of a large data set on
      free recall and found a highly specific pattern of statistical dependencies
      predicted by the model, in particular negative correlations between the number of
      words recalled and their average recall probability. Taken together, experimental
      and modeling results presented here reveal complex interactions between memory
      items during recall that severely constrain recall capacity. 

PMID- 25593299
TI  - The role of the basolateral amygdala in punishment.
AB  - Aversive stimuli not only support fear conditioning to their environmental
      antecedents, they also punish behaviors that cause their occurrence. The
      amygdala, especially the basolateral nucleus (BLA), has been critically
      implicated in Pavlovian fear learning but its role in punishment remains poorly
      understood. Here, we used a within-subjects punishment task to assess the role of
      the BLA in the acquisition and expression of punishment as well as aversive
      choice. Rats that pressed two individually presented levers for pellet rewards
      rapidly suppressed responding to one lever if it also caused footshock deliveries
      (punished lever) but continued pressing a second lever that did not cause
      footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol
      (BM) into the BLA significantly impaired the acquisition of this suppression. BLA
      inactivations using BM also reduced the expression of well-trained punishment.
      There was anatomical segregation within the BLA so that caudal, not rostral, BLA
      was implicated in punishment. However, when presented with punished and
      unpunished levers simultaneously in a choice test without deliveries of shock
      punisher, rats expressed a preference for unpunished over the punished lever and
      BLA inactivations had no effect on this preference. Taken together, these
      findings indicate that the BLA is important for both the acquisition and
      expression of punishment but not for aversive choice. This role appears to be
      linked to neurons in the caudal BLA, rather than rostral BLA, although the
      circuitry that contributes to this functional segregation is currently unknown,
      and is most parsimoniously interpreted as a role for caudal BLA in determining
      the aversive value of the shock punisher. 

PMID- 25593297
TI  - Serine 133 phosphorylation is not required for hippocampal CREB-mediated
      transcription and behavior.
AB  - The cAMP response element (CRE)-binding protein, CREB, is a transcription factor
      whose activity in the brain is critical for long-term memory formation.
      Phosphorylation of Ser133 in the kinase-inducible domain (KID), that in turn
      leads to the recruitment of the transcriptional coactivator CREB-binding protein
      (CBP), is thought to mediate the activation of CREB. However, the importance of
      phosphorylation for CREB binding to DNA and subsequent gene transcription in vivo
      is controversial. To definitively address the role of CREB phosphorylation in
      gene transcription and learning and memory, we derived mutant mice lacking the
      Ser133 phosphorylation site. These mice exhibit normal CREB-mediated gene
      transcription for a number of genes implicated in learning and memory processes.
      Furthermore these mice have no deficits in hippocampus- or striatum-dependent
      learning. Strikingly, our findings show that CREB phosphorylation at Ser133 is
      not necessary for CREB binding to CRE sites, CREB-mediated transcription, or CREB
      mediated behavioral phenotypes associated with learning and memory. 

PMID- 25593298
TI  - Isolating the incentive salience of reward-associated stimuli: value, choice, and
      persistence.
AB  - Sign- and goal-tracking are differentially associated with drug abuse-related
      behavior. Recently, it has been hypothesized that sign- and goal-tracking
      behavior are mediated by different neurobehavioral valuation systems, including
      differential incentive salience attribution. Herein, we used different
      conditioned stimuli to preferentially elicit different response types to study
      the different incentive valuation characteristics of stimuli associated with sign
      and goal-tracking within individuals. The results demonstrate that all stimuli
      used were equally effective conditioned stimuli; however, only a lever stimulus
      associated with sign-tracking behavior served as a robust conditioned reinforcer
      and was preferred over a tone associated with goal-tracking. Moreover, the
      incentive value attributed to the lever stimulus was capable of promoting
      suboptimal choice, leading to a significant reduction in reinforcers (food)
      earned. Furthermore, sign-tracking to a lever was more persistent than goal
      tracking to a tone under omission and extinction contingencies. Finally, a
      conditional discrimination procedure demonstrated that sign-tracking to a lever
      and goal-tracking to a tone were dependent on learned stimulus-reinforcer
      relations. Collectively, these results suggest that the different neurobehavioral
      valuation processes proposed to govern sign- and goal-tracking behavior are
      independent but parallel processes within individuals. Examining these systems
      within individuals will provide a better understanding of how one system comes to
      dominate stimulus-reward learning, thus leading to the differential role these
      systems play in abuse-related behavior. 

PMID- 25593300
TI  - Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic
      Targets in Phyllodes Tumors.
AB  - Phyllodes tumors are rare fibroepithelial tumors with variable clinical behavior
      accounting for a small subset of all breast neoplasms, yet little is known about
      the genetic alterations that drive tumor initiation and/or progression. Here,
      targeted next-generation sequencing (NGS) was used to identify somatic
      alterations in formalin-fixed paraffin-embedded (FFPE) patient specimens from
      malignant, borderline, and benign cases. NGS revealed mutations in mediator
      complex subunit 12 (MED12) affecting the G44 hotspot residue in the majority
      (67%) of cases spanning all three histologic grades. In addition, loss-of
      function mutations in p53 (TP53) as well as deleterious mutations in the tumor
      suppressors retinoblastoma (RB1) and neurofibromin 1 (NF1) were identified
      exclusively in malignant tumors. High-level copy-number alterations (CNA) were
      nearly exclusively confined to malignant tumors, including potentially clinically
      actionable gene amplifications in IGF1R and EGFR. Taken together, this study
      defines the genomic landscape underlying phyllodes tumor development, suggests
      potential molecular correlates to histologic grade, expands the spectrum of human
      tumors with frequent recurrent MED12 mutations, and identifies IGF1R and EGFR as
      potential therapeutic targets in malignant cases. IMPLICATIONS: Integrated
      genomic sequencing and mutational profiling provides insight into the molecular
      origin of phyllodes tumors and indicates potential druggable targets in malignant
      disease. Visual Overview:
      http://mcr.aacrjournals.org/content/early/2015/04/02/1541-7786.MCR-14
      0578/F1.large.jpg.

PMID- 25593301
TI  - CD47 Enhances In Vivo Functionality of Artificial Antigen-Presenting Cells.
AB  - PURPOSE: Artificial antigen-presenting cells, aAPC, have successfully been used
      to stimulate antigen-specific T-cell responses in vitro as well as in vivo.
      Although aAPC compare favorably with autologous dendritic cells in vitro, their
      effect in vivo might be diminished through rapid clearance by macrophages.
      Therefore, to prevent uptake and minimize clearance of aAPC by macrophages,
      thereby increasing in vivo functionality, we investigated the efficiency of
      "don't eat me" three-signal aAPC compared with classical two-signal aAPC.
      EXPERIMENTAL DESIGN: To generate "don't eat me" aAPC, CD47 was additionally
      immobilized onto classical aAPC (aAPC(CD47+)). aAPC and aAPC(CD47+) were analyzed
      in in vitro human primary T-cell and macrophage cocultures. In vivo efficiency
      was compared in a NOD/SCID T-cell proliferation and a B16-SIY melanoma model.
      RESULTS: This study demonstrates that aAPC(CD47+) in coculture with human
      macrophages show a CD47 concentration-dependent inhibition of phagocytosis,
      whereas their ability to generate and expand antigen-specific T cells was not
      affected. Furthermore, aAPC(CD47+)-generated T cells displayed equivalent killing
      abilities and polyfunctionality when compared with aAPC-generated T cells. In
      addition, in vivo studies demonstrated an enhanced stimulatory capacity and tumor
      inhibition of aAPC(CD47+) over normal aAPC in conjunction with diverging
      biodistribution in different organs. CONCLUSIONS: Our data for the first time
      show that aAPC functionalized with CD47 maintain their stimulatory capacity in
      vitro and demonstrate enhanced in vivo efficiency. Thus, these next-generation
      aAPC(CD47+) have a unique potential to enhance the application of the aAPC
      technology for future immunotherapy approaches.

PMID- 25593302
TI  - Hedgehog pathway inhibitors promote adaptive immune responses in basal cell
      carcinoma.
AB  - PURPOSE: Basal cell carcinomas (BCCs) are tumors ignored by immune surveillance.
      Activated Hedgehog (Hh) signaling within primary cilia is a key driver in the
      pathogenesis of BCCs. We examined immune alterations during treatment with
      systemic Hh inhibitors. EXPERIMENTAL DESIGN: We investigated biopsies from
      patients with BCC before (23 patients) and after 4 weeks of treatment (5
      patients) with Hh signaling inhibitor. Ber-Ep4, BCL-2, Ki-67, CD4, CD8, MHC class
      I, HLA-DR-class II, and SOX9 were analyzed by immunohistochemistry. Primary cilia
      were analyzed by double immunofluorescence of acetylated tubulin and SOX9.
      Differential gene expression for 84 cytokines and chemokines was analyzed in 3
      patients. RESULTS: After 4 weeks of treatment, we found reduction of Ki-67, SOX9,
      Ber-EP4, and BCL-2 expression in tumors associated with morphologic signs of
      squamous differentiation. In addition, the number of cilia-positive BCC cells was
      significantly decreased. An upregulation of MHC I expression on the cell
      membranes of residual tumor cells and an influx of CD4(+), HLA-DR-class II(+),
      and CD8(+) cells with invasion into the tumor cell nests were found. Finally,
      qPCR arrays showed the differential expression of genes involved in modulating
      immune responses. CONCLUSIONS: We show that Hh pathway inhibitor-induced tumor
      regression is accompanied by a dynamic change of the microenvironment with a
      disruption of immune privilege involving an influx of cytotoxic T cells,
      activation of the adaptive immune functions, and a profound alteration of the
      local chemokine/cytokine network.

PMID- 25593303
TI  - Improvements in Radiographic Progression-Free Survival Stratified by ERG Gene
      Status in Metastatic Castration-Resistant Prostate Cancer Patients Treated with
      Abiraterone Acetate.
AB  - PURPOSE: Gene fusions leading to androgen receptor-modulated ERG overexpression
      occur in up to 70% of metastatic castration-resistant prostate cancers (mCRPC).
      We assessed the association between ERG rearrangement status and clinical benefit
      from abiraterone acetate. EXPERIMENTAL DESIGN: COU-AA-302 is a phase III trial
      comparing abiraterone acetate and prednisone versus prednisone in chemotherapy
      naive mCRPC. ERG status was evaluated by FISH on archival tumors. End points
      included radiographic progression-free survival (rPFS), time to PSA progression
      (TTPP), rate of >=50% PSA decline from baseline, and overall survival (OS). Cox
      regression was used to evaluate association with time-to-event measures and
      Cochran-Mantel-Haenszel for PSA response. RESULTS: ERG status was defined for 348
      of 1,088 intention-to-treat patients. ERG was rearranged in 121 of 348 patients
      with confirmed ERG status (35%). Cancers with an ERG fusion secondary to deletion
      of 21q22 and increased copy number of fusion sequences (class 2+ Edel) had a
      greater improvement in rPFS after abiraterone acetate and prednisone [22 vs. 5.4
      months; HR (95% confidence interval, CI), 0.31 (0.15-0.68); P = 0.0033] than
      cancers with no ERG fusion [16.7 vs. 8.3 months; 0.53 (0.38-0.74); P = 0.0002] or
      other classes of ERG rearrangement. There was also greater benefit in this
      subgroup for TTPP. CONCLUSIONS: Both ERG-rearranged and wild-type cancers had a
      significant improvement in rPFS with abiraterone acetate and prednisone in the
      COU-AA-302 trial. However, our data suggest that 2+ Edel cancers, accounting for
      15% of all mCRPC patients and previously associated with a worse outcome, derived
      the greatest benefit.

PMID- 25593305
TI  - A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation.
AB  - The methyltransferase activity of the trithorax group (TrxG) protein MLL1 found
      within its COMPASS (complex associated with SET1)-like complex is allosterically
      regulated by a four-subunit complex composed of WDR5, RbBP5, Ash2L, and DPY30
      (also referred to as WRAD). We report structural evidence showing that in WRAD, a
      concave surface of the Ash2L SPIa and ryanodine receptor (SPRY) domain binds to a
      cluster of acidic residues, referred to as the D/E box, in RbBP5. Mutational
      analysis shows that residues forming the Ash2L/RbBP5 interface are important for
      heterodimer formation, stimulation of MLL1 catalytic activity, and erythroid cell
      terminal differentiation. We also demonstrate that a phosphorylation switch on
      RbBP5 stimulates WRAD complex formation and significantly increases KMT2 (lysine
      [K] methyltransferase 2) enzyme methylation rates. Overall, our findings provide
      structural insights into the assembly of the WRAD complex and point to a novel
      regulatory mechanism controlling the activity of the KMT2/COMPASS family of
      lysine methyltransferases.

PMID- 25593304
TI  - From equator to pole: splitting chromosomes in mitosis and meiosis.
AB  - During eukaryotic cell division, chromosomes must be precisely partitioned to
      daughter cells. This relies on a mechanism to move chromosomes in defined
      directions within the parental cell. While sister chromatids are segregated from
      one another in mitosis and meiosis II, specific adaptations enable the
      segregation of homologous chromosomes during meiosis I to reduce ploidy for
      gamete production. Many of the factors that drive these directed chromosome
      movements are known, and their molecular mechanism has started to be uncovered.
      Here we review the mechanisms of eukaryotic chromosome segregation, with a
      particular emphasis on the modifications that ensure the segregation of
      homologous chromosomes during meiosis I.

PMID- 25593306
TI  - The transcription factor Nerfin-1 prevents reversion of neurons into neural stem
      cells.
AB  - Cellular dedifferentiation is the regression of a cell from a specialized state
      to a more multipotent state and is implicated in cancer. However, the
      transcriptional network that prevents differentiated cells from reacquiring stem
      cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells,
      are a model for the regulation of stem cell self-renewal and differentiation.
      Here we show that the Drosophila zinc finger transcription factor Nervous fingers
      1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into
      NBs. Following Prospero-dependent neuronal specification in the ganglion mother
      cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation
      in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to
      multipotency and results in tumors in several neural lineages. Both the onset and
      rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on
      Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin
      1 is required for NB differentiation at the end of neurogenesis. RNA sequencing
      (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1
      administers its function by repression of self-renewing-specific and activation
      of differentiation-specific genes. Our findings support the model of
      bidirectional interconvertibility between neural stem cells and their post
      mitotic progeny and highlight the importance of the Nerfin-1-regulated
      transcriptional program in neuronal maintenance.

PMID- 25593307
TI  - ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis.
AB  - The initiation of pancreatic ductal adenocarcinoma (PDA) is linked to activating
      mutations in KRAS. However, in PDA mouse models, expression of oncogenic mutant
      KRAS during development gives rise to tumors only after a prolonged latency or
      following induction of pancreatitis. Here we describe a novel mouse model
      expressing ataxia telangiectasia group D complementing gene (ATDC, also known as
      TRIM29 [tripartite motif 29]) that, in the presence of oncogenic KRAS,
      accelerates pancreatic intraepithelial neoplasia (PanIN) formation and the
      development of invasive and metastatic cancers. We found that ATDC up-regulates
      CD44 in mouse and human PanIN lesions via activation of beta-catenin signaling,
      leading to the induction of an epithelial-to-mesenchymal transition (EMT)
      phenotype characterized by expression of Zeb1 and Snail1. We show that ATDC is up
      regulated by oncogenic Kras in a subset of PanIN cells that are capable of
      invading the surrounding stroma. These results delineate a novel molecular
      pathway for EMT in pancreatic tumorigenesis, showing that ATDC is a proximal
      regulator of EMT.

PMID- 25593308
TI  - FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating
      autophagy and receptor degradation.
AB  - Vacuolar protein-sorting 34 (Vps34), the catalytic subunit in the class III
      PtdIns3 (phosphatidylinositol 3) kinase complexes, mediates the production of
      PtdIns3P, a key intracellular lipid involved in regulating autophagy and receptor
      degradation. However, the signal transduction pathways by which extracellular
      signals regulate Vps34 complexes and the downstream cellular mechanisms are not
      well understood. Here we show that DNA damage-activated mitotic arrest and CDK
      activation lead to the phosphorylation of Vps34, which provides a signal to
      promote its ubiquitination and proteasomal degradation mediated by FBXL20 (an F
      box protein) and the associated Skp1 (S-phase kinase-associated protein-1)
      Cullin1 complex, leading to inhibition of autophagy and receptor endocytosis.
      Furthermore, we show that the expression of FBXL20 is regulated by p53-dependent
      transcription. Our study provides a molecular pathway by which DNA damage
      regulates Vps34 complexes and its downstream mechanisms, including autophagy and
      receptor endocytosis, through SCF (Skp1-Cul1-F-box)-mediated ubiquitination and
      degradation. Since the expression of FBXL20 is regulated by p53-dependent
      transcription, the control of Vps34 ubiquitination and proteasomal degradation by
      FBXL20 and the associated SCF complex expression provides a novel checkpoint for
      p53 to regulate autophagy and receptor degradation in DNA damage response.

PMID- 25593309
TI  - Screen identifies bromodomain protein ZMYND8 in chromatin recognition of
      transcription-associated DNA damage that promotes homologous recombination.
AB  - How chromatin shapes pathways that promote genome-epigenome integrity in response
      to DNA damage is an issue of crucial importance. We report that human bromodomain
      (BRD)-containing proteins, the primary "readers" of acetylated chromatin, are
      vital for the DNA damage response (DDR). We discovered that more than one-third
      of all human BRD proteins change localization in response to DNA damage. We
      identified ZMYND8 (zinc finger and MYND [myeloid, Nervy, and DEAF-1] domain
      containing 8) as a novel DDR factor that recruits the nucleosome remodeling and
      histone deacetylation (NuRD) complex to damaged chromatin. Our data define a
      transcription-associated DDR pathway mediated by ZMYND8 and the NuRD complex that
      targets DNA damage, including when it occurs within transcriptionally active
      chromatin, to repress transcription and promote repair by homologous
      recombination. Thus, our data identify human BRD proteins as key chromatin
      modulators of the DDR and provide novel insights into how DNA damage within
      actively transcribed regions requires chromatin-binding proteins to orchestrate
      the appropriate response in concordance with the damage-associated chromatin
      context.

PMID- 25593310
TI  - Genome-wide chromatin footprinting reveals changes in replication origin
      architecture induced by pre-RC assembly.
AB  - Start sites of DNA replication are marked by the origin recognition complex
      (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative
      complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the
      process is poorly understood within the local chromatin environment surrounding
      replication origins. To reveal how the chromatin architecture modulates origin
      selection and activation, we "footprinted" nucleosomes, transcription factors,
      and replication proteins at multiple points during the Saccharomyces cerevisiae
      cell cycle. Our nucleotide-resolution protein occupancy profiles resolved a
      precise ORC-dependent footprint at 269 origins in G2. A separate class of
      inefficient origins exhibited protein occupancy only in G1, suggesting that
      stable ORC chromatin association in G2 is a determinant of origin efficiency. G1
      nucleosome remodeling concomitant with pre-RC assembly expanded the origin
      nucleosome-free region and enhanced activation efficiency. Finally, the local
      chromatin environment restricts the loading of the Mcm2-7 double hexamer either
      upstream of or downstream from the ARS consensus sequence (ACS).

PMID- 25593311
TI  - Protein kinase Ymr291w/Tda1 is essential for glucose signaling in saccharomyces
      cerevisiae on the level of hexokinase isoenzyme ScHxk2 phosphorylation*.
AB  - The enzyme ScHxk2 of Saccharomyces cerevisiae is a dual-function hexokinase that
      besides its catalytic role in glycolysis is involved in the transcriptional
      regulation of glucose-repressible genes. Relief from glucose repression is
      accompanied by the phosphorylation of the nuclear fraction of ScHxk2 at serine 15
      and the translocation of the phosphoenzyme into the cytosol. Different studies
      suggest different serine/threonine protein kinases, Ymr291w/Tda1 or Snf1, to
      accomplish ScHxk2-S15 phosphorylation. The current paper provides evidence that
      Ymr291w/Tda1 is essential for that modification, whereas protein kinases
      Ydr477w/Snf1, Ynl307c/Mck1, Yfr014c/Cmk1, and Ykl126w/Ypk1, which are co-purified
      during Ymr291w/Tda1 tandem affinity purification, as well as protein kinase PKA
      and PKB homolog Sch9 are dispensable. Taking into account the detection of a
      significantly higher amount of the Ymr291w/Tda1 protein in cells grown in low
      glucose media as compared with a high-glucose environment, Ymr291w/Tda1 is likely
      to contribute to glucose signaling in S. cerevisiae on the level of ScHxk2-S15
      phosphorylation in a situation of limited external glucose availability. The
      evolutionary conservation of amino acid residue serine 15 in yeast hexokinases
      and its phosphorylation is illustrated by the finding that YMR291W/TDA1 of S.
      cerevisiae and the homologous KLLA0A09713 gene of Kluyveromyces lactis allow for
      cross-complementation of the respective protein kinase single-gene deletion
      strains. 

PMID- 25593312
TI  - Substrate tRNA recognition mechanism of eubacterial tRNA (m1A58)
      methyltransferase (TrmI).
AB  - TrmI generates N(1)-methyladenosine at position 58 (m(1)A58) in tRNA. The Thermus
      thermophilus tRNA(Phe) transcript was methylated efficiently by T. thermophilus
      TrmI, whereas the yeast tRNA(Phe) transcript was poorly methylated. Fourteen
      chimeric tRNA transcripts derived from these two tRNAs revealed that TrmI
      recognized the combination of aminoacyl stem, variable region, and T-loop. This
      was confirmed by 10 deletion tRNA variants: TrmI methylated transcripts
      containing the aminoacyl stem, variable region, and T-arm. The requirement for
      the T-stem itself was confirmed by disrupting the T-stem. Disrupting the
      interaction between T- and D-arms accelerated the methylation, suggesting that
      this disruption is included in part of the reaction. Experiments with 17 point
      mutant transcripts elucidated the positive sequence determinants C56, purine 57,
      A58, and U60. Replacing A58 with inosine and 2-aminopurine completely abrogated
      methylation, demonstrating that the 6-amino group in A58 is recognized by TrmI.
      T. thermophilus tRNAGGU(Thr)GGU(Thr) contains C60 instead of U60. The
      tRNAGGU(Thr) transcript was poorly methylated by TrmI, and replacing C60 with U
      increased the methylation, consistent with the point mutation experiments. A gel
      shift assay revealed that tRNAGGU(Thr) had a low affinity for TrmI than
      tRNA(Phe). Furthermore, analysis of tRNAGGU(Thr) purified from the trmI gene
      disruptant strain revealed that the other modifications in tRNA accelerated the
      formation of m(1)A58 by TrmI. Moreover, nucleoside analysis of tRNAGGU(Thr) from
      the wild-type strain indicated that less than 50% of tRNAGG(Thr) contained
      m(1)A58. Thus, the results from the in vitro experiments were confirmed by the in
      vivo methylation patterns.

PMID- 25593313
TI  - Equol, an isoflavone metabolite, regulates cancer cell viability and protein
      synthesis initiation via c-Myc and eIF4G.
AB  - Epidemiological studies implicate dietary soy isoflavones as breast cancer
      preventives, especially due to their anti-estrogenic properties. However, soy
      isoflavones may also have a role in promoting breast cancer, which has yet to be
      clarified. We previously reported that equol, a metabolite of the soy isoflavone
      daidzein, may advance breast cancer potential via up-regulation of the eukaryotic
      initiation factor 4GI (eIF4GI). In estrogen receptor negative (ER-) metastatic
      breast cancer cells, equol induced elevated levels of eIF4G, which were
      associated with increased cell viability and the selective translation of mRNAs
      that use non-canonical means of initiation, including internal ribosome entry
      site (IRES), ribosome shunting, and eIF4G enhancers. These mRNAs typically code
      for oncogenic, survival, and cell stress molecules. Among those mRNAs
      translationally increased by equol was the oncogene and eIF4G enhancer, c-Myc.
      Here we report that siRNA-mediated knockdown of c-Myc abrogates the increase in
      cancer cell viability and mammosphere formation by equol, and results in a
      significant down-regulation of eIF4GI (the major eIF4G isoform), as well as
      reduces levels of some, but not all, proteins encoded by mRNAs that are
      translationally stimulated by equol treatment. Knockdown of eIF4GI also markedly
      reduces an equol-mediated increase in IRES-dependent mRNA translation and the
      expression of specific oncogenic proteins. However, eIF4GI knockdown did not
      reciprocally affect c-Myc levels or cell viability. This study therefore
      implicates c-Myc as a potential regulator of the cancer-promoting effects of
      equol via up-regulation of eIF4GI and selective initiation of translation on
      mRNAs that utilize non-canonical initiation, including certain oncogenes. 

PMID- 25593314
TI  - Silver nanoparticles induce degradation of the endoplasmic reticulum stress
      sensor activating transcription factor-6 leading to activation of the NLRP-3
      inflammasome.
AB  - In the past decade, the increasing amount of nanoparticles (NP) and nanomaterials
      used in multiple applications led the scientific community to investigate the
      potential toxicity of NP. Many studies highlighted the cytotoxic effects of
      various NP, including titanium dioxide, zinc oxide, and silver nanoparticles
      (AgNP). In a few studies, endoplasmic reticulum (ER) stress was found to be
      associated with NP cytotoxicity leading to apoptosis in different cell types. In
      this study, we report for the first time that silver nanoparticles of 15 nm
      (AgNP15), depending on the concentration, induced different signature ER stress
      markers in human THP-1 monocytes leading to a rapid ER stress response with
      degradation of the ATF-6 sensor. Also, AgNP15 induced pyroptosis and activation
      of the NLRP-3 inflammasome as demonstrated by the processing and increased
      activity of caspase-1 and secretion of IL-1beta and ASC (apoptosis-associated
      speck-like protein containing a CARD domain) pyroptosome formation. Transfection
      of THP-1 cells with siRNA targeting NLRP-3 decreased the AgNP15-induced IL-1beta
      production. The absence of caspase-4 expression resulted in a significant
      reduction of pro-IL-1beta. However, caspase-1 activity was significantly higher
      in caspase-4-deficient cells when compared with WT cells. Inhibition of AgNP15
      induced ATF-6 degradation with Site-2 protease inhibitors completely blocked the
      effect of AgNP15 on pyroptosis and secretion of IL-1beta, indicating that ATF-6
      is crucial for the induction of this type of cell death. We conclude that AgNP15
      induce degradation of the ER stress sensor ATF-6, leading to activation of the
      NLRP-3 inflammasome regulated by caspase-4 in human monocytes. 

PMID- 25593315
TI  - Regulation of the sarcoplasmic reticulum calcium pump by divergent phospholamban
      isoforms in zebrafish.
AB  - The sarcoplasmic reticulum calcium pump (SERCA) is regulated by the small
      integral membrane proteins phospholamban (PLN) and sarcolipin (SLN). These
      regulators have homologous transmembrane regions, yet they differ in their
      cytoplasmic and luminal domains. Although the sequences of PLN and SLN are
      practically invariant among mammals, they vary in fish. Zebrafish (zf) appear to
      harbor multiple PLN isoforms, one of which contains 18 sequence variations and a
      unique luminal extension. Characterization of this isoform (zfPLN) revealed that
      SERCA inhibition and reversal by phosphorylation were comparable with human PLN.
      To understand the sequence variations in zfPLN, chimeras were created by
      transferring the N terminus, linker, and C terminus of zfPLN onto human PLN. A
      chimera containing the N-terminal domain resulted in a mild loss of function,
      whereas a chimera containing the linker domain resulted in a gain of function.
      This latter effect was due to changes in basic residues in the linker region of
      PLN. Removing the unique luminal domain of zfPLN ((53)SFHGM) resulted in loss of
      function, whereas adding this domain to human PLN had a minimal effect on SERCA
      inhibition. We conclude that the luminal extension contributes to SERCA
      inhibition but only in the context of zfPLN. Although this domain is distinct
      from the SLN luminal tail, zfPLN appears to use a hybrid PLN-SLN inhibitory
      mechanism. Importantly, the different zebrafish PLN isoforms raise the
      interesting possibility that sarcoplasmic reticulum calcium handling and cardiac
      contractility may be regulated by the differential expression of PLN functional
      variants. 

PMID- 25593316
TI  - Na+ transport by the A1AO-ATP synthase purified from Thermococcus onnurineus and
      reconstituted into liposomes.
AB  - The ATP synthase of many archaea has the conserved sodium ion binding motif in
      its rotor subunit, implying that these A1AO-ATP synthases use Na(+) as coupling
      ion. However, this has never been experimentally verified with a purified system.
      To experimentally address the nature of the coupling ion, we have purified the
      A1AO-ATP synthase from T. onnurineus. It contains nine subunits that are
      functionally coupled. The enzyme hydrolyzed ATP, CTP, GTP, UTP, and ITP with
      nearly identical activities of around 40 units/mg of protein and was active over
      a wide pH range with maximal activity at pH 7. Noteworthy was the temperature
      profile. ATP hydrolysis was maximal at 80  degrees C and still retained an
      activity of 2.5 units/mg of protein at 45  degrees C. The high activity of the
      enzyme at 45  degrees C opened, for the first time, a way to directly measure ion
      transport in an A1AO-ATP synthase. Therefore, the enzyme was reconstituted into
      liposomes generated from Escherichia coli lipids. These proteoliposomes were
      still active at 45  degrees C and coupled ATP hydrolysis to primary and
      electrogenic Na(+) transport. This is the first proof of Na(+) transport by an
      A1AO-ATP synthase and these findings are discussed in light of the distribution
      of the sodium ion binding motif in archaea and the role of Na(+) in the
      bioenergetics of archaea. 

PMID- 25593317
TI  - Acute inotropic and lusitropic effects of cardiomyopathic R9C mutation of
      phospholamban.
AB  - A naturally occurring R9C mutation of phospholamban (PLB) triggers cardiomyopathy
      and premature death by altering regulation of sarco/endoplasmic reticulum calcium
      ATPase (SERCA). The goal of this study was to investigate the acute physiological
      consequences of the R9C-PLB mutation on cardiomyocyte calcium kinetics and
      contractility. We measured the physiological consequences of R9C-PLB mutation on
      calcium transients and sarcomere shortening in adult cardiomyocytes. In contrast
      to studies of chronic R9C-PLB expression in transgenic mice, we found that acute
      expression of R9C-PLB exerts a positively inotropic and lusitropic effect in
      cardiomyocytes. Importantly, R9C-PLB exhibited blunted sensitivity to frequency
      potentiation and beta-adrenergic stimulation, two major physiological mechanisms
      for the regulation of cardiac performance. To identify the molecular mechanism of
      R9C pathology, we quantified the effect of R9C on PLB oligomerization and PLB
      SERCA binding. FRET measurements in live cells revealed that R9C-PLB exhibited an
      increased propensity for oligomerization, and this was further increased by
      oxidative stress. The R9C also decreased PLB binding to SERCA and altered the
      structure of the PLB-SERCA regulatory complex. The structural change after
      oxidative modification of R9C-PLB was similar to that observed after PLB
      phosphorylation. We conclude that R9C mutation of PLB decreases SERCA inhibition
      by decreasing the amount of the regulatory complex and altering its conformation.
      This has an acute inotropic/lusitropic effect but yields negative consequences of
      impaired frequency potentiation and blunted beta-adrenergic responsiveness. We
      envision a self-reinforcing mechanism beginning with phosphomimetic R9C-PLB
      oxidation and loss of SERCA inhibition, leading to impaired calcium regulation
      and heart failure. 

PMID- 25593318
TI  - Polyamine metabolism is sensitive to glycolysis inhibition in human neuroblastoma
      cells.
AB  - Polyamines are essential for cell proliferation, and their levels are elevated in
      many human tumors. The oncogene n-myc is known to potentiate polyamine
      metabolism. Neuroblastoma, the most frequent extracranial solid tumor in
      children, harbors the amplification of n-myc oncogene in 25% of the cases, and it
      is associated with treatment failure and poor prognosis. We evaluated several
      metabolic features of the human neuroblastoma cell lines Kelly, IMR-32, and SK-N
      SH. We further investigated the effects of glycolysis impairment in polyamine
      metabolism in these cell lines. A previously unknown linkage between glycolysis
      impairment and polyamine reduction is unveiled. We show that glycolysis
      inhibition is able to trigger signaling events leading to the reduction of N-Myc
      protein levels and a subsequent decrease of both ornithine decarboxylase
      expression and polyamine levels, accompanied by cell cycle blockade preceding
      cell death. New anti-tumor strategies could take advantage of the direct
      relationship between glucose deprivation and polyamine metabolism impairment,
      leading to cell death, and its apparent dependence on n-myc. Combined therapies
      targeting glucose metabolism and polyamine synthesis could be effective in the
      treatment of n-myc-expressing tumors. 

PMID- 25593319
TI  - Integrin alpha1-null mice exhibit improved fatty liver when fed a high fat diet
      despite severe hepatic insulin resistance.
AB  - Hepatic insulin resistance is associated with increased collagen. Integrin
      alpha1beta1 is a collagen-binding receptor expressed on hepatocytes. Here, we
      show that expression of the alpha1 subunit is increased in hepatocytes isolated
      from high fat (HF)-fed mice. To determine whether the integrin alpha1 subunit
      protects against impairments in hepatic glucose metabolism, we analyzed glucose
      tolerance and insulin sensitivity in HF-fed integrin alpha1-null (itga1(-/-)) and
      wild-type (itga1(+/+)) littermates. Using the insulin clamp, we found that
      insulin-stimulated hepatic glucose production was suppressed by ~50% in HF-fed
      itga1(+/+) mice. In contrast, it was not suppressed in HF-fed itga1(-/-) mice,
      indicating severe hepatic insulin resistance. This was associated with decreased
      hepatic insulin signaling in HF-fed itga1(-/-) mice. Interestingly, hepatic
      triglyceride and diglyceride contents were normalized to chow-fed levels in HF
      fed itga1(-/-) mice. This indicates that hepatic steatosis is dissociated from
      insulin resistance in HF-fed itga1(-/-) mice. The decrease in hepatic lipid
      accumulation in HF-fed itga1(-/-) mice was associated with altered free fatty
      acid metabolism. These studies establish a role for integrin signaling in
      facilitating hepatic insulin action while promoting lipid accumulation in mice
      challenged with a HF diet. 

PMID- 25593321
TI  - RNA toxicity and missplicing in the common eye disease fuchs endothelial corneal
      dystrophy.
AB  - Fuchs endothelial corneal dystrophy (FECD) is an inherited degenerative disease
      that affects the internal endothelial cell monolayer of the cornea and can result
      in corneal edema and vision loss in severe cases. FECD affects ~5% of middle-aged
      Caucasians in the United States and accounts for >14,000 corneal transplantations
      annually. Among the several genes and loci associated with FECD, the strongest
      association is with an intronic (CTG.CAG)n trinucleotide repeat expansion in the
      TCF4 gene, which is found in the majority of affected patients. Corneal
      endothelial cells from FECD patients harbor a poly(CUG)n RNA that can be
      visualized as RNA foci containing this condensed RNA and associated proteins.
      Similar to myotonic dystrophy type 1, the poly(CUG)n RNA co-localizes with and
      sequesters the mRNA-splicing factor MBNL1, leading to missplicing of essential
      MBNL1-regulated mRNAs. Such foci and missplicing are not observed in similar
      cells from FECD patients who lack the repeat expansion. RNA-Seq splicing data
      from the corneal endothelia of FECD patients and controls reveal hundreds of
      differential alternative splicing events. These include events previously
      characterized in the context of myotonic dystrophy type 1 and epithelial-to
      mesenchymal transition, as well as splicing changes in genes related to proposed
      mechanisms of FECD pathogenesis. We report the first instance of RNA toxicity and
      missplicing in a common non-neurological/neuromuscular disease associated with a
      repeat expansion. The FECD patient population with this (CTG.CAG)n trinucleotide
      repeat expansion exceeds that of the combined number of patients in all other
      microsatellite expansion disorders. 

PMID- 25593320
TI  - Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte
      kinase (RLK) using a novel covalent inhibitor PRN694.
AB  - Interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK or
      TXK) are essential mediators of intracellular signaling in both normal and
      neoplastic T-cells and natural killer (NK) cells. Thus, ITK and RLK inhibitors
      have therapeutic potential in a number of human autoimmune, inflammatory, and
      malignant diseases. Here we describe a novel ITK/RLK inhibitor, PRN694, which
      covalently binds to cysteine residues 442 of ITK and 350 of RLK and blocks kinase
      activity. Molecular modeling was utilized to design molecules that interact with
      cysteine while binding to the ATP binding site in the kinase domain. PRN694
      exhibits extended target residence time on ITK and RLK and is highly selective
      for a subset of the TEC kinase family. In vitro cellular assays confirm that
      PRN694 prevents T-cell receptor- and Fc receptor-induced cellular and molecular
      activation, inhibits T-cell receptor-induced T-cell proliferation, and blocks
      proinflammatory cytokine release as well as activation of Th17 cells. Ex vivo
      assays demonstrate inhibitory activity against T-cell prolymphocytic leukemia
      cells, and in vivo assays demonstrate durable pharmacodynamic effects on ITK,
      which reduces an oxazolone-induced delayed type hypersensitivity reaction. These
      data indicate that PRN694 is a highly selective and potent covalent inhibitor of
      ITK and RLK, and its extended target residence time enables durable attenuation
      of effector cells in vitro and in vivo. The results from this study highlight
      potential applications of this dual inhibitor for the treatment of T-cell- or NK
      cell-mediated inflammatory, autoimmune, and malignant diseases. 

PMID- 25593322
TI  - Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by
      phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent
      interaction of PDE3A1 with SERCA2.
AB  - Cyclic nucleotide phosphodiesterase 3A (PDE3) regulates cAMP-mediated signaling
      in the heart, and PDE3 inhibitors augment contractility in patients with heart
      failure. Studies in mice showed that PDE3A, not PDE3B, is the subfamily
      responsible for these inotropic effects and that murine PDE3A1 associates with
      sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2), phospholamban (PLB), and AKAP18
      in a multiprotein signalosome in human sarcoplasmic reticulum (SR).
      Immunohistochemical staining demonstrated that PDE3A co-localizes in Z-bands of
      human cardiac myocytes with desmin, SERCA2, PLB, and AKAP18. In human SR
      fractions, cAMP increased PLB phosphorylation and SERCA2 activity; this was
      potentiated by PDE3 inhibition but not by PDE4 inhibition. During gel filtration
      chromatography of solubilized SR membranes, PDE3 activity was recovered in
      distinct high molecular weight (HMW) and low molecular weight (LMW) peaks. HMW
      peaks contained PDE3A1 and PDE3A2, whereas LMW peaks contained PDE3A1, PDE3A2,
      and PDE3A3. Western blotting showed that endogenous HMW PDE3A1 was the principal
      PKA-phosphorylated isoform. Phosphorylation of endogenous PDE3A by rPKAc
      increased cAMP-hydrolytic activity, correlated with shift of PDE3A from LMW to
      HMW peaks, and increased co-immunoprecipitation of SERCA2, cav3, PKA regulatory
      subunit (PKARII), PP2A, and AKAP18 with PDE3A. In experiments with recombinant
      proteins, phosphorylation of recombinant human PDE3A isoforms by recombinant PKA
      catalytic subunit increased co-immunoprecipitation with rSERCA2 and rat rAKAP18
      (recombinant AKAP18). Deletion of the recombinant human PDE3A1/PDE3A2 N terminus
      blocked interactions with recombinant SERCA2. Serine-to-alanine substitutions
      identified Ser-292/Ser-293, a site unique to human PDE3A1, as the principal site
      regulating its interaction with SERCA2. These results indicate that
      phosphorylation of human PDE3A1 at a PKA site in its unique N-terminal extension
      promotes its incorporation into SERCA2/AKAP18 signalosomes, where it regulates a
      discrete cAMP pool that controls contractility by modulating phosphorylation
      dependent protein-protein interactions, PLB phosphorylation, and SERCA2 activity.

PMID- 25593323
TI  - A systematic survey of the Cys2His2 zinc finger DNA-binding landscape.
AB  - Cys2His2 zinc fingers (C2H2-ZFs) comprise the largest class of metazoan DNA
      binding domains. Despite this domain's well-defined DNA-recognition interface,
      and its successful use in the design of chimeric proteins capable of targeting
      genomic regions of interest, much remains unknown about its DNA-binding
      landscape. To help bridge this gap in fundamental knowledge and to provide a
      resource for design-oriented applications, we screened large synthetic protein
      libraries to select binding C2H2-ZF domains for each possible three base pair
      target. The resulting data consist of >160 000 unique domain-DNA interactions and
      comprise the most comprehensive investigation of C2H2-ZF DNA-binding interactions
      to date. An integrated analysis of these independent screens yielded DNA-binding
      profiles for tens of thousands of domains and led to the successful design and
      prediction of C2H2-ZF DNA-binding specificities. Computational analyses uncovered
      important aspects of C2H2-ZF domain-DNA interactions, including the roles of
      within-finger context and domain position on base recognition. We observed the
      existence of numerous distinct binding strategies for each possible three base
      pair target and an apparent balance between affinity and specificity of binding.
      In sum, our comprehensive data help elucidate the complex binding landscape of
      C2H2-ZF domains and provide a foundation for efforts to determine, predict and
      engineer their DNA-binding specificities. 

PMID- 25593324
TI  - Development of a unique epigenetic signature during in vivo Th17 differentiation.
AB  - Activated naive CD4(+) T cells are highly plastic cells that can differentiate
      into various T helper (Th) cell fates characterized by the expression of effector
      cytokines like IFN-gamma (Th1), IL-4 (Th2) or IL-17A (Th17). Although previous
      studies have demonstrated that epigenetic mechanisms including DNA demethylation
      can stabilize effector cytokine expression, a comprehensive analysis of the
      changes in the DNA methylation pattern during differentiation of naive T cells
      into Th cell subsets is lacking. Hence, we here performed a genome-wide methylome
      analysis of ex vivo isolated naive CD4(+) T cells, Th1 and Th17 cells. We could
      demonstrate that naive CD4(+) T cells share more demethylated regions with Th17
      cells when compared to Th1 cells, and that overall Th17 cells display the highest
      number of demethylated regions, findings which are in line with the previously
      reported plasticity of Th17 cells. We could identify seven regions located in
      Il17a, Zfp362, Ccr6, Acsbg1, Dpp4, Rora and Dclk1 showing pronounced
      demethylation selectively in ex vivo isolated Th17 cells when compared to other
      ex vivo isolated Th cell subsets and in vitro generated Th17 cells, suggesting
      that this unique epigenetic signature allows identifying and functionally
      characterizing in vivo generated Th17 cells. 

PMID- 25593326
TI  - Mycobacterium indicus pranii induces dendritic cell activation, survival, and
      Th1/Th17 polarization potential in a TLR-dependent manner.
AB  - MIP is a nonpathogenic, soil-borne predecessor of Mycobacterium avium. It has
      been reported previously that MIP possesses strong immunomodulatory properties
      and confers protection against experimental TB and tumor. DCs, by virtue of their
      unmatched antigen-presentation potential, play a critical role in activation of
      antitumor and antimycobacterial immune response. The effect of MIP on the
      behavior of DCs and the underlying mechanisms, however, have not been
      investigated so far. In the present study, we showed that MIP induces significant
      secretion of IL-6, IL-12p40, IL-10, and TNF-alpha by DCs and up-regulates the
      expression of costimulatory molecules CD40, CD80, and CD86. MIP(L) induced a
      significantly higher response compared with MIP(K). PI and Annexin V staining
      showed that MIP increases DC survival by inhibiting apoptosis. Consistently,
      higher expression of antiapoptotic proteins Bcl-2 and Bcl-xl was observed in MIP
      stimulated DCs. Cytokines, produced by naive T cells, cocultured with MIP
      stimulated DCs, showed that MIP promotes Th1/Th17 polarization potential in DCs.
      Response to MIP was lost in MyD88(-/-)DCs, underscoring the critical role of TLRs
      in MIP-induced DC activation. Further studies revealed that TLR2 and TLR9 are
      involved in DC activation by MIP(L), whereas MIP(K) activates the DCs through
      TLR2. Our findings establish the DC activation by MIP, define the behavior of MIP
      stimulated DCs, and highlight the role of TLRs in MIP-induced DC activation. 

PMID- 25593325
TI  - Primary and secondary siRNA synthesis triggered by RNAs from food bacteria in the
      ciliate Paramecium tetraurelia.
AB  - In various organisms, an efficient RNAi response can be triggered by feeding
      cells with bacteria producing double-stranded RNA (dsRNA) against an endogenous
      gene. However, the detailed mechanisms and natural functions of this pathway are
      not well understood in most cases. Here, we studied siRNA biogenesis from
      exogenous RNA and its genetic overlap with endogenous RNAi in the ciliate
      Paramecium tetraurelia by high-throughput sequencing. Using wild-type and mutant
      strains deficient for dsRNA feeding we found that high levels of primary siRNAs
      of both strands are processed from the ingested dsRNA trigger by the Dicer Dcr1,
      the RNA-dependent RNA polymerases Rdr1 and Rdr2 and other factors. We further
      show that this induces the synthesis of secondary siRNAs spreading along the
      entire endogenous mRNA, demonstrating the occurrence of both 3'-to-5' and 5'-to
      3' transitivity for the first time in the SAR clade of eukaryotes (Stramenopiles,
      Alveolates, Rhizaria). Secondary siRNAs depend on Rdr2 and show a strong
      antisense bias; they are produced at much lower levels than primary siRNAs and
      hardly contribute to RNAi efficiency. We further provide evidence that the
      Paramecium RNAi machinery also processes single-stranded RNAs from its bacterial
      food, broadening the possible natural functions of exogenously induced RNAi in
      this organism. 

PMID- 25593327
TI  - Overexpression of full-length cholesteryl ester transfer protein in SW872 cells
      reduces lipid accumulation.
AB  - Cells produce two cholesteryl ester transfer protein (CETP) isoforms, full-length
      and a shorter variant produced by alternative splicing. Blocking synthesis of
      both isoforms disrupts lipid metabolism and storage. To further define the role
      of CETP in cellular lipid metabolism, we stably overexpressed full-length CETP in
      SW872 cells. These CETP(+) cells had several-fold higher intracellular CETP and
      accumulated 50% less TG due to a 26% decrease in TG synthesis and 2.5-fold higher
      TG turnover rate. Reduced TG synthesis was due to decreased fatty acid uptake and
      impaired conversion of diglyceride to TG even though diacylglycerol
      acyltransferase activity was normal. Sterol-regulatory element binding protein 1
      mRNA levels were normal, and although PPARgamma expression was reduced, the
      expression of several of its target genes including adipocyte triglyceride
      lipase, FASN, and APOE was normal. CETP(+) cells contained smaller lipid
      droplets, consistent with their higher levels of perilipin protein family (PLIN)
      3 compared with PLIN1 and PLIN2. Intracellular CETP was mostly associated with
      the endoplasmic reticulum, although CETP near lipid droplets poorly colocalized
      with this membrane. A small pool of CETP resided in the cytoplasm, and a
      subfraction coisolated with lipid droplets. These data show that overexpression
      of full-length CETP disrupts lipid homeostasis resulting in the formation of
      smaller, more metabolically active lipid droplets. 

PMID- 25593329
TI  - Coagulation takes center stage in inflammation.

PMID- 25593328
TI  - Macrophage apoAI protects against dyslipidemia-induced dermatitis and
      atherosclerosis without affecting HDL.
AB  - Tissue cholesterol accumulation, macrophage infiltration, and inflammation are
      features of atherosclerosis and some forms of dermatitis. HDL and its main
      protein, apoAI, are acceptors of excess cholesterol from macrophages; this
      process inhibits tissue inflammation. Recent epidemiologic and clinical trial
      evidence questions the role of HDL and its manipulation in cardiovascular
      disease. We investigated the effect of ectopic macrophage apoAI expression on
      atherosclerosis and dermatitis induced by the combination of hypercholesterolemia
      and absence of HDL in mice. Hematopoietic progenitor cells were transduced to
      express human apoAI and transplanted into lethally irradiated LDL receptor(-/
      )/apoAI(-/-) mice, which were then placed on a high-fat diet for 16 weeks.
      Macrophage apoAI expression reduced aortic CD4(+) T-cell levels (-39.8%), lesion
      size (-25%), and necrotic core area (-31.6%), without affecting serum HDL or
      aortic macrophage levels. Macrophage apoAI reduced skin cholesterol by 39.8%,
      restored skin morphology, and reduced skin CD4(+) T-cell levels. Macrophage apoAI
      also reduced CD4(+) T-cell levels (-32.9%) in skin-draining lymph nodes but had
      no effect on other T cells, B cells, dendritic cells, or macrophages compared
      with control transplanted mice. Thus, macrophage apoAI expression protects
      against atherosclerosis and dermatitis by reducing cholesterol accumulation and
      regulating CD4(+) T-cell levels, without affecting serum HDL or tissue macrophage
      levels. 

PMID- 25593330
TI  - Langerhans cells: straight from blood to skin?

PMID- 25593331
TI  - Mutations of ETNK1 in aCML and CMML.

PMID- 25593332
TI  - Platelet GPIb: sensing force and responding.

PMID- 25593333
TI  - Anti-common gamma-chain antibody: one for all in GVHD.

PMID- 25593335
TI  - Composite end point of graft-versus-host disease-free, relapse-free survival
      after allogeneic hematopoietic cell transplantation.
AB  - The success of allogeneic hematopoietic cell transplantation (HCT) is typically
      assessed as individual complications, including graft-versus-host disease (GVHD),
      relapse, or death, yet no one factor can completely characterize cure without
      ongoing morbidity. We examined a novel composite end point of GVHD-free/relapse
      free survival (GRFS) in which events include grade 3-4 acute GVHD, systemic
      therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. In
      907 consecutive University of Minnesota allogeneic HCT recipients (2000-2012), 1
      year GRFS was 31% (95% confidence interval [CI] 28-34). Regression analyses
      showed age, disease risk, and donor type significantly influencing GRFS. Adults
      age 21+ had 2-fold worse GRFS vs children; GRFS did not differ beyond age 21.
      Adjusted for conditioning intensity, stem cell source, disease risk, age, and
      transplant year, HLA-matched sibling donor marrow resulted in the best GRFS (51%,
      95% CI 46-66), whereas HLA-matched sibling donor peripheral blood stem cells were
      significantly worse (25%, 95% CI 20-30, P = .01). GRFS after umbilical cord blood
      transplants and marrow from matched unrelated donors were similar (31%, 95% CI 27
      35 and 32%, 95% CI 22-42, respectively). Because GRFS measures freedom from
      ongoing morbidity and represents ideal HCT recovery, GRFS has value as a novel
      end point for benchmarking new therapies. 

PMID- 25593336
TI  - Defective PDI release from platelets and endothelial cells impairs thrombus
      formation in Hermansky-Pudlak syndrome.
AB  - Protein disulfide isomerase (PDI), secreted from platelets and endothelial cells
      after injury, is required for thrombus formation. The effect of platelet and
      endothelial cell granule contents on PDI-mediated thrombus formation was studied
      by intravital microscopy using a mouse model of Hermansky-Pudlak syndrome in
      which platelet dense granules are absent. Platelet deposition and fibrin
      generation were nearly absent, and extracellular PDI was significantly reduced in
      HPS6(-/-) mice after vascular injury. HPS6(-/-) platelets displayed impaired PDI
      secretion and impaired exocytosis of alpha granules, lysosomes, and T granules
      due to decreased sensitivity to thrombin, but these defects could be corrected by
      addition of subthreshold amounts of adenosine 5'-diphosphate (ADP). Human
      Hermansky-Pudlak syndrome platelets demonstrated similar characteristics.
      Infusion of wild-type platelets rescued thrombus formation in HPS6(-/-) mice.
      Human umbilical vein endothelial cells in which the HPS6 gene was silenced
      displayed impaired PDI secretion and exocytosis of Weibel-Palade bodies.
      Defective thrombus formation in Hermansky-Pudlak syndrome, associated with
      impaired exocytosis of residual granules in endothelial cells and platelets, the
      latter due to deficiency of ADP, is characterized by a defect in T granule
      secretion, a deficiency in extracellular PDI secretion, and impaired fibrin
      generation and platelet aggregation. Hermansky-Pudlak syndrome is an example of a
      hereditary disease whereby impaired PDI secretion contributes to a bleeding
      phenotype. 

PMID- 25593337
TI  - Maintenance of mouse hematopoietic stem cells ex vivo by reprogramming cellular
      metabolism.
AB  - The difficulty in maintaining the reconstituting capabilities of hematopoietic
      stem cells (HSCs) in culture outside of the bone marrow microenvironment has
      severely limited their utilization for clinical therapy. This hurdle is largely
      due to the differentiation of long-term stem cells. Emerging evidence suggests
      that energy metabolism plays an important role in coordinating HSC self-renewal
      and differentiation. Here, we show that treatment with alexidine dihydrochloride,
      an antibiotic and a selective inhibitor of the mitochondrial phosphatase Ptpmt1,
      which is crucial for the differentiation of HSCs, reprogrammed cellular
      metabolism from mitochondrial aerobic metabolism to glycolysis, resulting in a
      remarkable preservation of long-term HSCs ex vivo in part through hyperactivation
      of adenosine 5'-monophosphate-activated protein kinase (AMPK). In addition,
      inhibition of mitochondrial metabolism and activation of AMPK by metformin, a
      diabetes drug, also decreased differentiation and helped maintain stem cells in
      culture. Thus, manipulating metabolic pathways represents an effective new
      strategy for ex vivo maintenance of HSCs. 

PMID- 25593339
TI  - Fewer colon cancer patients have surgery but survival is increasing, US study
      shows.

PMID- 25593340
TI  - Signs of depression and apathy precede memory problems in Alzheimer's disease,
      study shows.

PMID- 25593338
TI  - Clinical disease due to enterovirus D68 in adult hematologic malignancy patients
      and hematopoietic cell transplant recipients.
AB  - The United States Centers for Disease Control and Prevention reported over 1000
      cases of severe respiratory disease in pediatric patients associated with
      enterovirus D68 (EV-D68) in the fall of 2014. We sought to identify and define
      the clinical burden of disease due to EV-D68 in adult patients with hematologic
      malignancy or undergoing hematopoietic cell transplant (HCT). Real-time reverse
      transcriptase polymerase chain reaction (PCR) for EV-D68 was performed on all
      respiratory samples positive for human rhinovirus (HRV) or negative for all
      respiratory viruses by a laboratory-developed respiratory viral PCR panel from
      August 11, 2014, to November 7, 2014. Presumptive cases were defined as those
      with an EV-D68 PCR cycle threshold (CT) at least 4 cycles lower than the HRV CT
      for HRV-positive samples or any EV-D68 CT value for HRV-negative samples.
      Sequencing of a 150-bp fragment of the 5' noncoding region confirmed EV-D68 in 16
      of 506 respiratory samples. Eight patients had a history of hematologic
      malignancy, and 6 of these had undergone HCT. Presentation ranged from mild upper
      respiratory symptoms to respiratory failure. EV-D68 can infect adult patients
      with hematologic malignancy and HCT recipients and may be associated with severe
      respiratory disease. Current commercial diagnostic assays cannot differentiate EV
      D68 from other enteroviruses or HRV, and improved rapid diagnostic tools are
      needed. 

PMID- 25593342
TI  - CCR 20th anniversary commentary: a chimeric antibody, C225, inhibits EGFR
      activation and tumor growth.
AB  - Murine mAb 225 was effective against the EGFR tyrosine kinase and inhibited tumor
      growth in preclinical studies. A phase I trial showed safety, tumor localization,
      and satisfactory pharmacokinetics. Human:murine chimeric C225 retained biologic
      activity, which was essential for the conduct of subsequent combination therapy
      trials and eventual regulatory approval.

PMID- 25593343
TI  - Evolutionarily conserved signaling pathways: acting in the shadows of acute
      myelogenous leukemia's genetic diversity.
AB  - Acute myelogenous leukemia stem cells (AML-LSC) give rise to the leukemic bulk
      population and maintain disease. Relapse can arise from residual LSCs that have
      distinct sensitivity and dependencies when compared with the AML bulk. AML-LSCs
      are driven by genetic and epigenomic changes, and these alterations influence
      prognosis and clonal selection. Therapies targeting these molecular aberrations
      have been developed and show promising responses in advanced clinical trials;
      however, so far success with LSCs has been limited. Besides the genetic
      diversity, AML-LSCs are critically influenced by the microenvironment, and a
      third crucial aspect has recently come to the fore: A group of evolutionarily
      conserved signaling pathways such as canonical Wnt signaling, Notch signaling, or
      the Hedgehog pathway can be essential for maintenance of AML-LSC but may be
      redundant for normal hematopoietic stem cells. In addition, early reports suggest
      also regulators of cell polarity may also influence hematopoietic stem cells and
      AML biology. Interactions between these pathways have been investigated recently
      and suggest a network of signaling pathways involved in regulation of self
      renewal and response to oncogenic stress. Here, we review how recent discoveries
      on regulation of AML-LSC-relevant evolutionarily conserved pathways may open
      opportunities for novel treatment approaches eradicating residual disease.

PMID- 25593344
TI  - DUSP1 expression induced by HDAC1 inhibition mediates gefitinib sensitivity in
      non-small cell lung cancers.
AB  - PURPOSE: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related
      death worldwide. Patients with NSCLC with EGFR-activating mutation benefit
      greatly by gefitinib, an EGFR tyrosine kinase inhibitor. However, acquired
      resistance limits its clinical use. Histone deacetylases (HDAC) are oncoproteins
      associated with cancer progression and drug resistance. Here, we disclosed that
      inhibition of HDAC1 induced protein phosphatase DUSP1 upregulation to overcome
      gefitinib-acquired resistance. EXPERIMENTAL DESIGN: The effect of HDAC1
      inhibition restored gefitinib sensitivity was assessed by in vitro MTT and
      apoptotic assays, and in vivo xenograft and orthotopic lung cancer mouse models.
      Protein phosphatase array was used to detect DUSP1 expression.
      Immunohistochemical staining and quantitative PCR were used to analyze DUSP1
      expression in clinical NSCLC specimens. RESULTS: Gefitinib-resistant NSCLC cells
      showed HDAC1 overexpression, and its knockdown sensitized resistant cells to
      gefitinib in vitro and in preclinical models through DUSP1 expression.
      Overexpression of DUSP1 in resistant cells restored gefitinib sensitivity by
      inhibiting EGFR signaling and inducing apoptosis, whereas its knockdown in
      sensitive cells conferred gefitinib resistance. A novel HDAC inhibitor, WJ-26210
      2, in combination with gefitinib upregulated DUSP1 expression to exert in vitro
      and in vivo synergistic effect on inactivation of EGFR signaling, growth
      inhibition, and apoptosis. Clinically, high DUSP1 level was correlated with
      delayed emergence of gefitinib-acquired resistance. CONCLUSIONS: Decreased DUSP1
      might be a mechanism responsible for gefitinib resistance, and DUSP1 might be a
      biomarker for gefitinib efficacy. HDAC1 inhibition-induced DUSP1 upregulation
      could be a promising strategy to overcome gefitinib-acquired resistance. Clin
      Cancer Res; 21(2); 428-38. (c)2015 AACR.

PMID- 25593345
TI  - Sputum microRNA biomarkers for identifying lung cancer in indeterminate solitary
      pulmonary nodules.
AB  - PURPOSE: The early detection of lung cancer in heavy smokers by low-dose CT
      (LDCT) can reduce the mortality. However, LDCT screening increases the number of
      indeterminate solitary pulmonary nodules (SPN) in asymptomatic individuals,
      leading to overdiagnosis. Making a definitive preoperative diagnosis of malignant
      SPNs has been a clinical challenge. We have demonstrated that sputum miRNAs could
      provide potential biomarkers for lung cancer. Here, we aimed to develop sputum
      miRNA biomarkers for diagnosis of malignant SPNs. EXPERIMENTAL DESIGN: Using
      quantitative RT-PCR, we evaluated expressions of 13 sputum miRNAs, previously
      identified sputum miRNA signatures of lung cancer, in a training set of 122
      patients with either malignant (n = 60) or benign SPNs (n = 62) to define a panel
      of biomarkers. We then validated the biomarker panel in an internal testing set
      of 136 patients with either malignant (n = 67) or benign SPNs (n = 69), and an
      external testing cohort of 155 patients with either malignant (n = 76) or benign
      SPNs (n = 79). RESULTS: In the training set, a panel of three miRNA biomarkers
      (miRs21, 31, and 210) was developed, producing 82.93% sensitivity and 87.84%
      specificity for identifying malignant SPNs. The sensitivity and specificity of
      the biomarkers in the two independent testing cohorts were 82.09% and 88.41%,
      80.52% and 86.08%, respectively, confirming the diagnostic value. CONCLUSIONS:
      Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy
      smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective
      study in a large population to validate the biomarkers is needed.

PMID- 25593346
TI  - Complement activation and rituximab distribution in CNS NHL--letter.

PMID- 25593347
TI  - The 2015 Nucleic Acids Research Database Issue and molecular biology database
      collection.
AB  - The 2015 Nucleic Acids Research Database Issue contains 172 papers that include
      descriptions of 56 new molecular biology databases, and updates on 115 databases
      whose descriptions have been previously published in NAR or other journals.
      Following the classification that has been introduced last year in order to
      simplify navigation of the entire issue, these articles are divided into eight
      subject categories. This year's highlights include RNAcentral, an international
      community portal to various databases on noncoding RNA; ValidatorDB, a validation
      database for protein structures and their ligands; SASBDB, a primary repository
      for small-angle scattering data of various macromolecular complexes; MoonProt, a
      database of 'moonlighting' proteins, and two new databases of protein-protein and
      other macromolecular complexes, ComPPI and the Complex Portal. This issue also
      includes an unusually high number of cancer-related databases and other databases
      dedicated to genomic basics of disease and potential drugs and drug targets. The
      size of NAR online Molecular Biology Database Collection,
      http://www.oxfordjournals.org/nar/database/a/, remained approximately the same,
      following the addition of 74 new resources and removal of 77 obsolete web sites.
      The entire Database Issue is freely available online on the Nucleic Acids
      Research web site (http://nar.oxfordjournals.org/). 

PMID- 25593348
TI  - PlasmoGEM, a database supporting a community resource for large-scale
      experimental genetics in malaria parasites.
AB  - The Plasmodium Genetic Modification (PlasmoGEM) database
      (http://plasmogem.sanger.ac.uk) provides access to a resource of modular,
      versatile and adaptable vectors for genome modification of Plasmodium spp.
      parasites. PlasmoGEM currently consists of >2000 plasmids designed to modify the
      genome of Plasmodium berghei, a malaria parasite of rodents, which can be
      requested by non-profit research organisations free of charge. PlasmoGEM vectors
      are designed with long homology arms for efficient genome integration and carry
      gene specific barcodes to identify individual mutants. They can be used for a
      wide array of applications, including protein localisation, gene interaction
      studies and high-throughput genetic screens. The vector production pipeline is
      supported by a custom software suite that automates both the vector design
      process and quality control by full-length sequencing of the finished vectors.
      The PlasmoGEM web interface allows users to search a database of finished knock
      out and gene tagging vectors, view details of their designs, download vector
      sequence in different formats and view available quality control data as well as
      suggested genotyping strategies. We also make gDNA library clones and
      intermediate vectors available for researchers to produce vectors for themselves.

PMID- 25593349
TI  - The neXtProt knowledgebase on human proteins: current status.
AB  - neXtProt (http://www.nextprot.org) is a human protein-centric knowledgebase
      developed at the SIB Swiss Institute of Bioinformatics. Focused solely on human
      proteins, neXtProt aims to provide a state of the art resource for the
      representation of human biology by capturing a wide range of data, precise
      annotations, fully traceable data provenance and a web interface which enables
      researchers to find and view information in a comprehensive manner. Since the
      introductory neXtProt publication, significant advances have been made on three
      main aspects: the representation of proteomics data, an extended representation
      of human variants and the development of an advanced search capability built
      around semantic technologies. These changes are presented in the current neXtProt
      update. 

PMID- 25593350
TI  - Methyl-CpG-binding domain protein MBD7 is required for active DNA demethylation
      in Arabidopsis.
AB  - Although researchers have established that DNA methylation and active
      demethylation are dynamically regulated in plant cells, the molecular mechanism
      for the regulation of active DNA demethylation is not well understood. By using
      an Arabidopsis (Arabidopsis thaliana) line expressing the Promoter RESPONSIVE TO
      DEHYDRATION 29A:LUCIFERASE (ProRD29A:LUC) and Promoter cauliflower mosaic virus
      35S:NEOMYCIN PHOSPHOTRANSFERASE II (Pro35S:NPTII) transgenes, we isolated an mbd7
      (for methyl-CpG-binding domain protein7) mutant. The mbd7 mutation causes an
      inactivation of the Pro35S:NPTII transgene but does not affect the expression of
      the ProRD29A:LUC transgene. The silencing of the Pro35S:NPTII reporter gene is
      associated with DNA hypermethylation of the reporter gene. MBD7 interacts
      physically with REPRESSOR OF SILENCING5/INCREASED DNA METHYLATION2, a protein in
      the small heat shock protein family. MBD7 prefers to target the genomic loci with
      high densities of DNA methylation around chromocenters. The Gypsy-type long
      terminal repeat retrotransposons mainly distributed around chromocenters are most
      affected by mbd7 in all transposons. Our results suggest that MBD7 is required
      for active DNA demethylation and antisilencing of the genomic loci with high
      densities of DNA methylation in Arabidopsis. 

PMID- 25593352
TI  - Tuberculosis of hip: A current concept review.
AB  - Tuberculosis (TB) of the hip is second to spine only hence a good number of cases
      are visiting the medical facilities every year. Many present in the advanced
      stage of the disease due to delayed diagnosis. In early stages of TB of hip,
      there is a diagnostic dilemma when plain X-rays are negative. In the present
      time, diagnostic modalities have improved from the days when diagnosis was based
      essentially on clinicoradiological presentation alone. By the time definite
      radiological changes appear on plain X-ray, the disease has moderately advanced.
      The modern diagnostic facilities like ultrasonography (USG) or magnetic resonance
      imaging of the hip joint, USG guided aspiration of synovial fluid and obtaining
      the material for polymerase chain reaction and tissue diagnosis must be utilized.
      In the treatment, current emphasis is more on mobility with stability at hip.
      Joint debridement, skeletal traction, and mobilization exercises may give more
      satisfying results as compared to the immobilization by hip spica. Adults with
      advanced arthritis and healed infection should be informed and discussed the
      various treatment modalities including the joint replacement. More and more
      surgeons are taking up the challenge of putting the total hip replacement in the
      active stage of the disease. Until the long term results in active disease are
      well established, we recommend it for the healed disease only in selected cases. 

PMID- 25593353
TI  - Management of Perthes' disease.
AB  - The main complication of Perthes' disease is femoral head deformation. Evidence
      from the literature highlights two important factors related to the cause and
      timing of this complication. (1) Extrusion of the femoral head appears to be a
      major factor that leads to femoral head deformation. (2) Deformation of the
      femoral head occurs in the latter part of the stage of fragmentation. The
      likelihood of preventing femoral head deformation is over 16 times higher if
      extrusion is reversed or prevented by the early stage of fragmentation than if
      done later. Several treatment options have been described in children who present
      later in the course of the disease but the outcomes of all these measures do not
      compare with those of early intervention. 

PMID- 25593354
TI  - Treatment of neglected femoral neck fracture.
AB  - Intra-capsular femoral neck fractures are seen commonly in elderly people
      following a low energy trauma. Femoral neck fracture has a devastating effect on
      the blood supply of the femoral head, which is directly proportional to the
      severity of trauma and displacement of the fracture. Various authors have
      described a wide array of options for treatment of neglected/nonunion (NU)
      femoral neck fracture. There is lack of consensus in general, regarding the best
      option. This Instructional course article is an analysis of available treatment
      options used for neglected femoral neck fracture in the literature and attempt to
      suggest treatment guides for neglected femoral neck fracture. We conducted the
      "Pubmed" search with the keywords "NU femoral neck fracture and/or neglected
      femoral neck fracture, muscle-pedicle bone graft in femoral neck fracture,
      fibular graft in femoral neck fracture and valgus osteotomy in femoral neck
      fracture." A total of 203 print articles were obtained as the search result.
      Thirty three articles were included in the analysis and were categorized into
      four subgroups based on treatment options. (a) treated by muscle-pedicle bone
      grafting (MPBG), (b) closed/open reduction internal fixation and fibular grafting
      (c) open reduction and internal fixation with valgus osteotomy, (d) miscellaneous
      procedures. The data was pooled from all groups for mean neglect, the type of
      study (prospective or retrospective), classification used, procedure performed,
      mean followup available, outcome, complications, and reoperation if any. The
      outcome of neglected femoral neck fracture depends on the duration of neglect, as
      the changes occurring in the fracture area and fracture fragments decides the
      need and type of biological stimulus required for fracture union. In stage I and
      stage II (Sandhu's staging) neglected femoral neck fracture osteosynthesis with
      open reduction and bone grafting with MPBG or Valgus Osteotomy achieves fracture
      union in almost 90% cases. However, in stage III with or without AVN, the results
      of osteosynthesis are poor and the choice of treatment is replacement
      arthroplasty (hemi or total). 

PMID- 25593351
TI  - ARACINs, Brassicaceae-specific peptides exhibiting antifungal activities against
      necrotrophic pathogens in Arabidopsis.
AB  - Plants have developed a variety of mechanisms to cope with abiotic and biotic
      stresses. In a previous subcellular localization study of hydrogen peroxide
      responsive proteins, two peptides with an unknown function (designated ARACIN1
      and ARACIN2) have been identified. These peptides are structurally very similar
      but are transcriptionally differentially regulated during abiotic stresses during
      Botrytis cinerea infection or after benzothiadiazole and methyl jasmonate
      treatments. In Arabidopsis (Arabidopsis thaliana), these paralogous genes are
      positioned in tandem within a cluster of pathogen defense-related genes. Both
      ARACINs are small, cationic, and hydrophobic peptides, known characteristics for
      antimicrobial peptides. Their genes are expressed in peripheral cell layers prone
      to pathogen entry and are lineage specific to the Brassicaceae family. In vitro
      bioassays demonstrated that both ARACIN peptides have a direct antifungal effect
      against the agronomically and economically important necrotrophic fungi B.
      cinerea, Alternaria brassicicola, Fusarium graminearum, and Sclerotinia
      sclerotiorum and yeast (Saccharomyces cerevisiae). In addition, transgenic
      Arabidopsis plants that ectopically express ARACIN1 are protected better against
      infections with both B. cinerea and A. brassicicola. Therefore, we can conclude
      that both ARACINs act as antimicrobial peptides. 

PMID- 25593356
TI  - Limb salvage: When, where, and how?
AB  - From an era where amputation was the only option to the current day function
      preserving resections and complex reconstructions has been a major advance in the
      treatment of musculoskeletal sarcomas. The objectives of extremity reconstruction
      after oncologic resection include providing skeletal stability where necessary,
      adequate wound coverage to allow early subsequent adjuvant therapy, optimising
      the aesthetic outcome and preservation of functional capability with early return
      to function. This article highlights the concepts of surgical margins in
      oncology, discusses the principles governing safe surgical resection in these
      tumors and summarises the current modalities and recent developments relevant to
      reconstruction after limb salvage. The rationale of choice of a particular
      resection modality and the unique challenges of reconstruction in skeletally
      immature individuals are also discussed. Striking the right balance between
      adequate resection, while yet retaining or reconstructing tissue for acceptable
      function and cosmesis is a difficult task. Complications are not uncommon and
      patients and their families need to be counseled regarding the potential setbacks
      that may occur in the course of their eventual road to recovery, Limb salvage
      entails a well orchestrated effort involving various specialties and better
      outcomes are likely to be achieved with centralization of expertise at regional
      centers. 

PMID- 25593355
TI  - Management of femoral head osteonecrosis: Current concepts.
AB  - Osteonecrosis of femoral head (ONFH) is a disabling condition of young
      individuals with ill-defined etiology and pathogenesis. Remains untreated, about
      70-80% of the patients progress to secondary hip arthritis. Both operative and
      nonoperative treatments have been described with variable success rate. Early
      diagnosis and treatment is the key for success in preserving the hip joint. Once
      femoral head collapses (>2 mm) or if there is secondary degeneration, hip
      conservation procedures become ineffective and arthroplasty remains the only
      better option. We reviewed 157 studies that evaluate different treatment
      modalities of ONFH and then a final consensus on treatment was made. 

PMID- 25593357
TI  - Stem cell therapy in spinal trauma: Does it have scientific validity?
AB  - Stem cell-based interventions aim to use special regenerative cells (stem cells)
      to facilitate neuronal function beyond the site of the injury. Many studies
      involving animal models of spinal cord injury (SCI) suggest that certain stem
      cell-based therapies may restore function after SCI. Currently, in case of spinal
      cord injuries, new discoveries with clinical implications have been continuously
      made in basic stem cell research, and stem cell-based approaches are advancing
      rapidly toward application in patients. There is a huge base of preclinical
      evidence in vitro and in animal models which suggests the safety and clinical
      efficacy of cellular therapies after SCI. Despite this, data from clinical
      studies is not very encouraging and at times confounding. Here, we have attempted
      to cover preclinical and clinical evidence base dealing with safety, feasibility
      and efficacy of cell based interventions after SCI. The limitations of
      preclinical data and the reasons underlying its failure to translate in a
      clinical setting are also discussed. Based on the evidence base, it is suggested
      that a multifactorial approach is required to address this situation. Need for
      standardized, stringently designed multi-centric clinical trials for obtaining
      validated proof of evidence is also highlighted. 

PMID- 25593358
TI  - Management of thoracolumbar spine trauma: An overview.
AB  - Thoracolumbar spine fractures are common injuries that can result in significant
      disability, deformity and neurological deficit. Controversies exist regarding the
      appropriate radiological investigations, the indications for surgical management
      and the timing, approach and type of surgery. This review provides an overview of
      the epidemiology, biomechanical principles, radiological and clinical evaluation,
      classification and management principles. Literature review of all relevant
      articles published in PubMed covering thoracolumbar spine fractures with or
      without neurologic deficit was performed. The search terms used were
      thoracolumbar, thoracic, lumbar, fracture, trauma and management. All relevant
      articles and abstracts covering thoracolumbar spine fractures with and without
      neurologic deficit were reviewed. Biomechanically the thoracolumbar spine is
      predisposed to a higher incidence of spinal injuries. Computed tomography
      provides adequate bony detail for assessing spinal stability while magnetic
      resonance imaging shows injuries to soft tissues (posterior ligamentous complex
      [PLC]) and neurological structures. Different classification systems exist and
      the most recent is the AO spine knowledge forum classification of thoracolumbar
      trauma. Treatment includes both nonoperative and operative methods and selected
      based on the degree of bony injury, neurological involvement, presence of
      associated injuries and the integrity of the PLC. Significant advances in imaging
      have helped in the better understanding of thoracolumbar fractures, including
      information on canal morphology and injury to soft tissue structures. The ideal
      classification that is simple, comprehensive and guides management is still
      elusive. Involvement of three columns, progressive neurological deficit,
      significant kyphosis and canal compromise with neurological deficit are accepted
      indications for surgical stabilization through anterior, posterior or combined
      approaches. 

PMID- 25593361
TI  - Anomalous biceps origin from the rotator cuff.
AB  - Variations in the origin of the long head of biceps tendon (LHBT) have been
      described in literature; however, its clinical significance remains uncertain. We
      describe in this report, the history, physical examination and the arthroscopic
      findings in a patient who had an anomalous origin of the LHBT from the rotator
      cuff, resulting in restriction of range of motion. This anomalous origin of the
      long head of biceps tendon causing capsular contracture and restriction of
      movements leading to secondary internal impingement, has not been extensively
      reported in the literature. Shoulder arthroscopists should be aware that,
      although, an uncommon clinical condition, the aberrant congenital origin of the
      LHBT from the rotator cuff can rarely become pathologic in middle age and lead to
      shoulder dysfunction. In such cases, release of the anomalous band may be
      required, along with the treatment of other concomitant intraarticular
      pathologies in the glenohumeral joint. 

PMID- 25593360
TI  - A reduction clamp for an aiming component in associated acetabular fractures.
AB  - BACKGROUND: The treatment of acetabular fractures is complex and requires
      specialized equipment. However, all currently available instruments have some
      disadvantages. A new reduction clamp that can firmly enable reduction and not
      hinder subsequent fixation procedures for some special fracture types is needed.
      MATERIALS AND METHODS: In this study, we introduce a new acetabular clamp and its
      preliminary clinical application in three T-shaped acetabular fractures. RESULTS:
      This new clamp can successfully pull the posterior column back to the anterior
      column and firmly maintain the reduction. This clamp's aiming plate can
      facilitate the insertion of long lag screws. The clamp is also easy to assemble
      and use. CONCLUSION: This reduction clamp is a useful instrument that can
      facilitate open reduction and internal fixation of acetabular fractures.

PMID- 25593359
TI  - Management of skeletal metastases: An orthopaedic surgeon's guide.
AB  - Skeletal metastasis is a common cause of severe morbidity, reduction in quality
      of life (QOL) and often early mortality. Its prevalence is rising due to a higher
      rate of diagnosis, better systemic treatment, longer lives with the disease and
      higher disease burden rate. As people with cancer live longer and with rising
      sensitivity of body imaging and surveillance, the incidence of pathological
      fracture, metastatic epidural cord compression is rising and constitutes a
      challenge for the orthopedic surgeon to maintain their QOL. Metastatic disease is
      no longer a death sentence condemning patients to "terminal care." In the era of
      multidisciplinary care and effective systemic targeted and nontargeted therapy,
      patient expectations of QOL, even during palliative end of care period is high.
      We lay emphasis on proving the diagnosis of metastasis by biopsy and
      histopathology and discuss imaging modalities to help estimate fracture risk and
      map disease extent. This article discusses at length the evidence and decision
      making process of various modalities to treat skeletal metastasis. The modalities
      range from radiation including image-guided, stereotactic and whole body
      radiation, systemic targeted or hormonal therapy, spinal decompression with or
      without stabilization, extended curettage with stabilization, resection in select
      cases with megaprosthetic or biological reconstruction, percutaneous procedures
      using radio frequency ablation, cementoplasties and discusses the role of
      emerging modalities like high frequency ultrasound-guided ablation, cryotherapy
      and whole body radionuclide therapy. The focus lies on the role of
      multidisciplinary care, which considers complex decisions on patient centric
      prognosis, comorbidities, cost, feasibility and expectations in order to maximize
      outcomes on QOL issues. 

PMID- 25593362
TI  - Nonunion in a distal radius metaphyseal fracture in a child: Role of intact
      periosteal sleeve in management.
AB  - We present an adolescent with distal radius nonunion following an open fracture
      and failed surgery which eventually united when the length and stability was
      restored for eight weeks duration. The intact periosteal sleeve at the nonunion
      site formed new bone when its tension was restored by gradual differential
      distraction. This case report highlights the possibility of stimulating bony
      union in an established atrophic nonunion by distracting the minimally disturbed
      soft tissue and thick osteogenic periosteal envelope in the paediatric age group.

PMID- 25593363
TI  - External iliac artery thrombus masquerading as sciatic nerve palsy in anterior
      column fracture of the acetabulum.
AB  - We report a case of ischemic neuropathy of the sciatic nerve in a patient with an
      anterior column fracture of the acetabulum operated by ilioinguinal approach. It
      resulted from occlusion of the blood supply to the sciatic nerve. There were no
      signs of a vascular insult until ischemic changes ensued on the 6(th)
      postoperative day on the lateral part of great toe. The patient underwent
      crossover femoro-femoral bypass grafting and there was a complete reversal of the
      ischemic changes at 6 months. The sciatic nerve palsy continued to recover until
      the end of 1 year; by which time the only deficit was a Grade 4 power in the
      extensor hallucis longus (EHL) and the extensor digitorum longus (EDL). There was
      no further recovery at 2 years followup. 

PMID- 25593364
TI  - Quenching of TryptophanFluorescence in Unfolded Cytochrome c: A Biophysics
      Experiment for Physical Chemistry Students.

PMID- 25593365
TI  - Utilization of physicochemical variables developed from changes in sensory
      attributes and consumer acceptability to predict the shelf life of fresh-cut
      mango fruit.
AB  - Sensory evaluation is the ideal tool for shelf-life determination. With the
      objective to develop an easy shelf-life indicator, color (L*, a*, b*, chroma and
      hue angle), total soluble solids (TSS), firmness (F), pH, acidity, and the
      sensory attributes of appearance, brightness, browning, odor, flavor, texture,
      color, acidity and sweetness were evaluated in fresh cut mangoes (FCM) stored at
      5, 10, 15 and 20  degrees C. Overall acceptability was evaluated by consumers.
      Correlation analysis between sensory attributes and physicochemical variables was
      carried out. Physicochemical cut-off points based on sensory attributes and
      consumer acceptability was obtained by regression analysis and utilized to
      estimate FCM shelf-life by kinetic models fitted to each variable. The validation
      of the model was done by comparing the shelf life estimated by kinetic models and
      consumers. It was recorded large correlations between appearance, brightness, and
      color with L*; appearance and color with chroma and hue angle; sweetness and
      flavor with TSS, and between F and texture. The shelf life estimated based on
      consumer using a 9 point hedonic scale was in the range of 10-12, 2.3-2.6, 1.3
      1.5 and 1.0-1.1 days for 5, 10, 15 and 20  degrees C. It was recorded large
      correlation coefficients between the shelf life estimated by consumer
      acceptability scores and physicochemical variables. Kinetic models based on
      physicochemical variables showed a tendency to overestimate the shelf life as
      compared with the models bases on the sensory attributes. It was concluded that
      physicochemical variables can be used as a tool to estimate the FCM shelf life. 

PMID- 25593366
TI  - Influence of different desapping agents on the incidence of sapburn, ripening
      behaviour and quality of mango.
AB  - Sapburn injury in mango is regarded as the most serious problem as it reduces the
      aesthetic appeal and downgrade the fruit quality with considerable economic
      losses. For the control of sapburn injury, physiologically mature mango fruits of
      cv. Chausa were harvested along with 5-8 cm stalk attached. Immediately after
      harvesting, fruits were de-stemmed and treated with different desapping agent
      solutions [calcium hydroxide (1 %), sodium hydroxide (1 %), alum (0.5 and 1 %)]
      by dipping them for 5 min. In control fruits, the pedicels were removed and sap
      was allowed to spread freely over the fruit surface. After treatment application,
      fruits were air-dried and stored at ambient condition (30 +/- 2  degrees C) for
      12 days. Among the treatments, fruits desapped with sodium hydroxide (1 %) showed
      significantly lower (7.6-fold) sapburn injury followed by alum (0.5 %) treatment
      than control. Respiration and ethylene evolution rates were also significantly
      suppressed and delayed with sodium hydroxide (1 %) treatment. Fruit firmness and
      functional properties like, antioxidant capacity, total carotenoids and total
      phenolics content were also found higher in sodium hydroxide (1 %) treated
      fruits. Pectin methyl esterase and polygalacturonase enzyme activity were
      recorded higher in fruits of control and calcium hydroxide treatment however; it
      was suppressed by sodium hydroxide and alum treatments. Fruit quality parameters
      like color, total soluble solids, titratable acidity and total sugars content
      were found higher in calcium hydroxide and sodium hydroxide treated fruits than
      control and alum treated fruits. 

PMID- 25593368
TI  - Non-destructive measurement of fracturability and chewiness of apple by FT-NIRS.
AB  - In order to assess quickly and non-destructively the fracturability and chewiness
      of apple fruit by FT-NIR spectra in the wavelength range of 4000 cm(-1)-12000 cm(
      1), multivariate models were built using multiple linear regression (MLR),
      partial least squares regression (PLSR), and principal component regression
      (PCR). Fracturability and chewiness reference data were instrumentally measured
      using a Texture Profile Analysis (TPA) test. The effects of various pre
      processing methods of the spectroscopic data on the performance of the
      multivariate models were analyzed. Standard normal variate transformation (SNV),
      multiplicative scatter correction (MSC), Min-Max normalization(MMN) and first
      derivative (FD) were tested. The performance of the fracturability prediction
      models was better for the PLSR model (R(2) = 0.91, RMSEP = 101.90) than for the
      PCR and MLR models. With regard to chewiness, the performance of the PCR model
      (R(2) = 0.88, RMSEP = 13.46) was similar to the one of the PLSR model but better
      than the one of the MLR model. The results demonstrated that NIR spectra together
      with stoichiometry could determine precisely fracturability and chewiness of
      apple, and the predictive ability of the models developed by other methods may be
      improved in the future. 

PMID- 25593367
TI  - Phenolic compounds, antioxidant activity and insulinotropic effect of extracts
      prepared from grape (Vitis vinifera L) byproducts.
AB  - Grape byproducts are a rich source of phenolics having immense medicinal
      properties, but usually wasted from juice/wine processing industries. The present
      study investigates the phenolic antioxidants and the insulinotropic effect of
      extracts prepared from seed, skin and stems of two red wine grape cultivars: Pusa
      Navarang and Merlot. Pusa Navarang cultivar has shown high amounts of total
      phenolics (95.8 mg/ml), flavonoids (30.5 mg/ml) and flavan-3-ols (21.8 mg/ml) in
      seed extract and total anthocyanin (4.9 mg/ml) in its skin extract as compared to
      Merlot cultivar. As determined using HPLC, higher amounts of catechin hydrate
      (14909 mg/l) and epicatechin (9299 mg/l) were observed in its seed extract, while
      quercetin hydrate (5849 mg/l) was abundant in its skin extract. Similarly, ferric
      reducing antioxidant power (FRAP) and ABTS(+). [2,2'-azinobis (3
      ethylbenzothiazoline)-6-sulfonic acid] and DPPH. (1,1-diphenyl-2-picrylhy-
      drazyl) radicals scavenging, were higher in its seed extract, respectively being
      134.8 mg/ml of Quercetin equivalent (QE), 18.7 mM of trolox equivalent (TE) and
      33.5 mM of TE. Strong correlation was obtained between FRAP and total phenolics,
      flavonoids and flavan-3-ols contents with correlation coefficients (r(2)) of
      0.915, 0.738 and 0.838 respectively. Interestingly, there was a 2-8 fold increase
      in insulin secretion by isolated mice pancreatic islets at 5.5 mM and 16.5 mM
      glucose concentration in presence of various extracts. Overall, the seed, skin
      and stem byproducts of both cultivars are rich sources of phenolics and
      antioxidants and represent a source of new insulin secretagogues. 

PMID- 25593369
TI  - Effect of One-methylcyclopropene (1-MCP) and chlorine dioxide (ClO2) on
      preservation of green walnut fruit and kernel traits.
AB  - The effect of the ethylene receptor competitor 1-methylcyclopropene (1-MCP) and
      the legally approved disinfectant chlorine dioxide (ClO2) on preservation of the
      green walnut fruit during storage was investigated. Green Chinese walnut fruit
      cv. Xilin No.2 was harvested on commercial maturity and stored at 0-1  degrees C
      after the fruit was treated by water (control), 80 mg L(-1)ClO2 (ClO2), 0.5 MUL
      L(-1)1-MCP (1-MCP), or combination treatment of 80 mg L(-1) ClO2 with either 0.1
      MUL L(-1) 1-MCP (0.1 1-MCP+ ClO2) or 0.5 MUL L(-1) 1-MCP (0.5 1-MCP+ ClO2).
      During storage, respiration, ethylene production, phenolics content,
      antioxidative activity, weight changes, decay of the fruit and kernel traits of
      acid value, peroxide value,free fatty were measured. All treatments decreased
      postharvest respiration intensity in different degrees and inhibited ethylene
      production peak. ClO2 increased the total phenol and flavonoid content of the
      green fruit compared with other treatments and the control (P < 0.05), but not
      did the total antioxidant activity for this treatment. After 42-day storage, ClO2
      remained higher fresh weight and lower decay index than control, while 1-MCP
      increased the fruit decay index. Final acid values of kernel from ClO2, control
      and 0.1 1-MCP+ ClO2 were not different from their initial values, which from 0.5
      1-MCP increased. Final peroxide value for kernel from ClO2 showed no change
      during storage but increased at least 1.0-fold for other treatments. ClO2
      preserved 99.9 % of initial free fatty acid, similar to that for the control
      (99.8 %), whereas 0.5 1-MCP preserved only 95.7 %. ClO2 is of potential in decay
      retardation and kernel traits maintenance of green walnut fruit, whereas the 1
      MCP has a negative effect for decay control on walnut. 

PMID- 25593370
TI  - Effect of processing conditions on the quality characteristics of barley chips.
AB  - The aim of the present study was to study the effect of lime concentration,
      frying temperature and frying time on quality characteristics of barley chips.
      Effect of salt concentration and packaging material on the quality and stability
      of the product was also studied during 180 days of storage under ambient
      conditions. An increase in fat content of chips was observed with the increase in
      lime concentration, frying temperature and time, whereas a decreasing trend was
      observed in moisture content of chips. An increase in amylose content of chips
      was observed during frying. However, it was found that the amylopectin in chips
      decreased during frying as frying temperature and time was increased. An increase
      in colour difference (DeltaE) and crispness was noted in chips during frying as
      frying temperature and time increased. With the increase in lime concentration
      (0.5 and 1.0 %) both DeltaE and break force of chips was found decreased. The
      results further revealed that there was gradual decrease in fat (%) and
      amylopectin (%) during storage, whereas moisture (%) and amylose (%) increased
      during storage period. Organoleptic evaluation of the product revealed that
      scores of colour, texture, flavour and over all acceptability decrease during
      storage. However the treatment (salt 2 % and aluminium based laminate) recorded
      better score with respect to colour, flavour, texture and overall acceptability. 

PMID- 25593371
TI  - Quality of Opuntia robusta and its use in development of mayonnaise-like product.
AB  - The aim of this study was to characterize Opuntia robusta parenchyma and mucilage
      as foodstuffs. Solute absorption of Opuntia robusta parenchyma was studied,
      mucilage was used to develop a mayonnaise-like product as substitute emulsifier
      alternative to egg yolk and oil substitute. Shelf life of mayonnaise-like product
      was evaluated. Scanning electron microscopy demonstrated that oxalate calcium
      crystal were present in the Opuntia robusta parenchyma and mucilage with druses
      morphology; whereas that in the mayonnaise-like product were not observed calcium
      oxalate crystals, due probably to the product pH is acidic. The heat treatment of
      parenchyma at 50  degrees C, 65 degrees Brix, had highest influence on the solute
      absorption (about 35 %). Results revealed that best mixture was the formulated
      with 26.79 % oil, 62.50 % mucilage and 10.71 % whey protein. Mucilage was the
      component showing the highest effect on all textural characteristics of
      mayonnaise-like product. The storage temperature had highest effect on the
      textural characteristics of mayonnaise-like product than storage time. With the
      right combination of mucilage of Opuntia, oil and whey protein, it is possible to
      develop a low-fat mayonnaise with functional properties similar to those of
      commercial mayonnaise. 

PMID- 25593372
TI  - Effect of acid hydrolysis combined with heat moisture treatment on structure and
      physicochemical properties of corn starch.
AB  - Modification of starch led to new products with new desirable properties. Corn
      starch samples modified by acid hydrolysis combined with heat moisture treatment
      (AH-HMT) were made by changing pH, moisture content and treated temperature.
      After modification, swelling power at temperature higher than 75  degrees C of
      corn starches decreased while solubility of the starches increased. After AH-HMT,
      pasting temperature (PT) of all treated starch samples increased. But lower peak
      viscosity (PKV), trough viscosity (TV) and break down (BD) of most treated starch
      samples were observed. AH-HMT increased the gel hardness of all treated starches.
      And the biggest hardness of modified starch gel was 148.419 g, improving 93.471 g
      compared with native starch gel. The melting temperatures (To, Tp, Tc) of
      modified starch increased, but the melting range and ?H decreased. The X-ray
      pattern remained practically unchanged with or without AH-HMT. Acid hydrolysis
      combined with heat moisture treatment (AH-HMT) improved the functional properties
      of corn starch. 

PMID- 25593373
TI  - Resveratrol content and antioxidant properties of underutilized fruits.
AB  - In the present study, resveratrol content and antioxidant properties of
      underutilized fruits such as Jamun (Syzygium cumini L.), Jackfruit (Artocarpus
      heterophyllus) and Mulberry (Morus rubra) were investigated keeping Grape (Vitis
      vinifera) as a reference. Ethanol/water (80:20 v/v) extracts of different parts
      of fruit samples including skin, pulp and seeds were analyzed by HPLC and MS for
      the quantification of resveratrol. Total polyphenols, flavonoids, DPPH scavenging
      activity and total antioxidant capacity were also investigated. Among the samples
      analyzed, mulberry fruit (whole) showed highest resveratrol content (50.61 MUg g(
      1) dry weight) followed by jamun seed (34.87 MUg g(-1) dry weight), jamun pulp
      (13.70 MUg g(-1) dry weight) and skin of jamun (11.19 MUg g(-1) dry weight).
      Jamun seed extract exhibited the highest polyphenol content (55.54 mg gallic acid
      equivalent g(-1) dry weight) and highest antioxidant property (IC50 value-0.40 mg
      ml(-1)). The results suggest that underutilized fruits high in resveratrol and
      other polyphenols can be used as functional beverages. 

PMID- 25593374
TI  - Training Teachers to use Evidence-Based Practices for Autism: Examining
      Procedural Implementation fidelity.
AB  - The purpose of this study was to examine the extent to which public school
      teachers implemented evidence-based interventions for students with autism in the
      way these practices were designed. Evidence-based practices for students with
      autism are rarely incorporated into community settings, and little is known about
      the quality of implementation. An indicator of intervention quality is procedural
      implementation fidelity (the degree to which a treatment is implemented as
      prescribed). Procedural fidelity likely affects student outcomes. This project
      examined procedural implementation fidelity of three evidence-based practices
      used in a randomized trial of a comprehensive program for students with autism in
      partnership with a large, urban school district. Results indicate that teachers
      in public school special education classrooms can learn to implement evidence
      based strategies; however they require extensive training, coaching, and time to
      reach and maintain moderate procedural implementation fidelity. Procedural
      fidelity over time, and across intervention strategies is examined.

PMID- 25593375
TI  - Improved Synthesis of and Nucleophilic Addition to 2-Formyl-2-Cyclohexenone.
AB  - A preparation of 2-formyl-2-cyclohexenone in nearly quantitative yield and purity
      of approximately 95% is described. It is scalable and has been extended to the
      synthesis of the 5- and 7-membered ring homologs with comparable yields.
      Conditions have also been developed for the successful conjugate addition of
      dimethylmalonate to 2-formyl-2-cyclohexenone, in good and scalable yield (60%).
      This result has been extended to 5 other nucleophile classes, and the
      dimethylmalonate conjugate addition has been demonstrated with 2-formyl-2
      cyclopentenone and 2-formyl-2-cycloheptenone.

PMID- 25593377
TI  - The Role of Simple Feature Differences in Infants' Recognition of Faces.
AB  - The features of a face which define its age or sex appear to play a more
      important role than do the number of simple feature differences between like aged
      or same sex faces in the 5- to 6-month infant's recognition of face photos.

PMID- 25593378
TI  - Environmental Quality and Fertility: The Effects of Plant Density, Species
      Richness, and Plant Diversity on Fertility Limitation.
AB  - The relationship between the environment and population has been of concern for
      centuries and climate change is making this an even more pressing area of study.
      In poor rural areas declining environmental conditions may elicit changes in
      family related behaviors. This paper explores this relationship in rural Nepal
      looking specifically at how plant density, species richness, and plant diversity
      are related to women's fertility limitation behavior. Taking advantage of a
      unique data set with detailed micro-level environmental measures and individual
      fertility behavior I link geographically weighted measures of flora at one point
      in time to women's later contraceptive use as a way to examine this complex
      relationship. I find a significant, positive relationship between plant density,
      species richness, and plant diversity and the timing of contraceptive use. Women
      in poor environmental conditions are less likely to terminate childbearing, or do
      so later, and therefore more likely to have larger families.

PMID- 25593376
TI  - Thinking positively: The genetics of high intelligence.
AB  - High intelligence (general cognitive ability) is fundamental to the human capital
      that drives societies in the information age. Understanding the origins of this
      intellectual capital is important for government policy, for neuroscience, and
      for genetics. For genetics, a key question is whether the genetic causes of high
      intelligence are qualitatively or quantitatively different from the normal
      distribution of intelligence. We report results from a sibling and twin study of
      high intelligence and its links with the normal distribution. We identified
      360,000 sibling pairs and 9000 twin pairs from 3 million 18-year-old males with
      cognitive assessments administered as part of conscription to military service in
      Sweden between 1968 and 2010. We found that high intelligence is familial,
      heritable, and caused by the same genetic and environmental factors responsible
      for the normal distribution of intelligence. High intelligence is a good
      candidate for "positive genetics" - going beyond the negative effects of DNA
      sequence variation on disease and disorders to consider the positive end of the
      distribution of genetic effects.

PMID- 25593380
TI  - Bimodal gastroretentive drug delivery systems of lamotrigine: formulation and
      evaluation.
AB  - Gastroretentive bimodal drug delivery systems of lamotrigine were developed using
      immediate release and extended release segments incorporated in a hydroxypropyl
      methylcellulose capsule and in vitro and in vivo evaluations were conducted. In
      vivo radiographic studies were carried out for the optimized formulation in
      healthy human volunteers with replacement of drug polymer complex by barium
      sulphate and the floating time was noted. Here the immediate release segment
      worked as loading dose and extended release segment as maintenance dose. The
      results of release studies of formulations with hydrophillic matrix to
      formulations with dual matrix hydroxypropyl methylcellulose acetate succinate
      shown that as the percentage of polymer increased, the release decreased.
      Selected formulation F2 having F-Melt has successfully released the drug within
      one hour and hydrophillic matrix composing polyethylene oxide with 5%
      hydroxypropyl methylcellulose acetate succinate showed a lag time of one hour and
      then extended its release up to 12th hour with 99.59% drug release following zero
      order kinetics with R(2) value of 0.989. The Korsmeyer-Peppas equation showed the
      R(2) value to be 0.941 and n value was 1.606 following non-Fickian diffusion
      pattern with supercase II relaxation mechanism. Here from extended release tablet
      the drug released slowly from the matrix while floating. 

PMID- 25593379
TI  - Immunomodulatory effects of triphala and its individual constituents: a review.
AB  - The role of plant extracts and Ayurvedic polyherbal preparations in treating
      various ailments has been acknowledged since time immemorial. Studies based on
      the effect of these extracts in treatment of different diseases have also been
      well documented. Indian medicinal literature also emphasizes the synergistic
      effect of polyherbal drugs in restoring and rejuvenating immune system. This
      review focuses on the immunomodulatory potential of the polyherbal preparation,
      Triphala and its three constituents, Terminalia bellerica, Terminalia chebula and
      Emblica officinalis. The role of Triphala and its extract has been emphasized in
      stimulating neutrophil function. Under stress condition such as noise, Triphala
      significantly prevents elevation of IL-4 levels as well as corrects decreased IL
      2 and IFN-gamma levels. Under the condition of inflammatory stress its
      immunosuppressive activity is attributed to its inhibitory action on complement
      system, humoral immunity, cell mediated immunity and mitogen-induced T-lymphocyte
      proliferation. The aqueous and alcoholic extracts of the individual constituents
      reportedly enhance especially the macrophage activation due to their free radical
      scavenging activity and the ability to neutralize reactive oxygen species. This
      study thus concludes the use of Triphala and its three individual constituents as
      potential immunostimulants and/or immunosuppressants further suggests them to be
      a better alternative for allopathic immunomodulators. 

PMID- 25593381
TI  - Synergistic effect of hydrotrope and surfactant on solubility and dissolution of
      atorvastatin calcium: screening factorial design followed by ratio optimization.
AB  - The present study was aimed at investigating the effect of hydrotrope and
      surfactant on poor solubility of atorvastatin calcium. Excipients screening
      followed by factorial design was performed to study effect of excipients and
      manufacturing methods on solubility of drug. Three independent factors (carrier,
      surfactant and manufacturing method) were evaluated at two levels using
      solubility as a dependant variable. Solid-state characterisation was performed
      using Fourier transform infrared spectroscopy and differential scanning
      calorimetry. Optimised complex were incorporated into orally disintegrating micro
      tablets and in vitro dissolution test was performed. Nicotinamide, Plasdone and
      sodium dodecyl sulphate were emerged as promising excipients from excipient
      screening. General regression analysis revealed only the type of carrier has
      significantly enhanced (P<0.05) the solubility of drug while other factors were
      found to be nonsignificant. Ratio optimisation trial revealed that drug to
      nicotinamide ratio is more critical in enhancing the solubility of drug (40 fold
      increases in solubility compared to pure drug) in comparison to drug-surfactant
      ratio; however the presence of surfactant deemed essential. Significantly higher
      rate and extent of dissolution was observed from solid dispersion complex and
      tablets compared to dissolution of pure drug (P<0.05). Study revealed hydrotrope
      and surfactant have synergistic effect on solubility and dissolution of
      atorvastatin calcium and this can be explored further. 

PMID- 25593382
TI  - Variations in physicochemical properties of a traditional mercury-based
      nanopowder formulation: need for standard manufacturing practices.
AB  - Rasasindura is a mercury-based nanopowder synthesized using natural products
      through mechanothermal processing. It has been used in the Ayurvedic system of
      medicine since time immemorial for various therapeutic purposes such as
      rejuvenation, treatment of syphilis and in genital disorders. Rasasindura is said
      to be composed of mercury, sulphur and organic moieties derived from the
      decoction of plant extracts used during its synthesis. There is little scientific
      understanding of the preparation process so far. Though metallic mercury is
      incorporated deliberately for therapeutic purposes, it certainly raises toxicity
      concerns. The lack of gold standards in manufacturing of such drugs leads to a
      variation in the chemical composition of the final product. The objective of the
      present study was to assess the physicochemical properties of Rasasindura samples
      of different batches purchased from different manufacturers and assess the extent
      of deviation and gauge its impact on human health. Modern characterization
      techniques were employed to analyze particle size and morphology, surface area,
      zeta potential, elemental composition, crystallinity, thermal stability and
      degradation. Average particle size of the samples observed through scanning
      electron microscope ranged from 5-100 nm. Mercury content was found to be between
      84 and 89% from elemental analysis. Despite batch-to-batch and manufacturer-to
      manufacturer variations in the physicochemical properties, all the samples
      contained mercury in the form of HgS. These differences in the physicochemical
      properties may ultimately impact its biological outcome. 

PMID- 25593384
TI  - A Facile Synthesis, In vitro Antiinflammatory and Antioxidant activity of Novel
      Benzimidazolylpyrano[2,3-d][1,3]thiazolocarbonitriles.
AB  - The synthesis benzimidazolylpyrano [2,3-d] [1,3] thiazolocarbonitriles (5a-j)
      were achieved by cyclocondensation of arylidene amino-benzo[d]imidazole-2-thiols
      (3a-j) with mercaptoacetic acid followed by cyclization with 2
      (phenylmethylene)malononitrile. Further more, the present study aimed at the
      evaluation of in vitro antiinflammatory activity and antioxidant activity of
      synthetic compounds. All tested compounds showed appreciable activity against the
      standard drugs. 

PMID- 25593383
TI  - Profile of atherosclerotic risk factors and management in patients of peripheral
      arterial disease at a tertiary care teaching hospital of north India.
AB  - Peripheral arterial disease, being a manifestation of systemic atherosclerosis,
      carries a high risk of adverse cardiovascular events. Secondary medical
      prevention therapies of same magnitude as that for coronary artery disease are
      recommended for peripheral arterial disease patients also. Available evidence
      indicates that this condition commonly remains underdiagnosed and undertreated.
      There is lack of any report about management of these patients in India. The
      objectives of the present study were to characterize the atherosclerotic risk
      factor profile and pattern of drug prescription for patients of peripheral
      arterial disease at a tertiary care teaching hospital and to compare this
      management with standard guidelines. Data were collected from prescriptions of
      patients attending cardiothoracic and vascular surgery outpatient department with
      diagnosis of atherosclerotic peripheral arterial disease from July 2012 to Jun
      2013. One hundred twenty prescriptions were analysed. The mean age (+/-SD) of
      patients was 53+/-7.18 years and 23.3% were females. History of smoking, either
      past or present, was present in 91.6% patients. History of ischemic heart disease
      was present in 25%, while 26.7% patients were diabetic. Mean number of
      cardiovascular risk factors was 2.6. The percentage of eligible patients who were
      receiving a particular drug was 100% for aspirin and statins, 48.3% for
      angiotensin converting enzyme inhibitors, 46.7% for beta blockers and 66.7% for
      cilostazol. The vascular surgeons of this centre are using antiplatelet agents
      and statins adequately for peripheral arterial disease. The prescription of
      angiotensin converting enzyme inhibitors, beta blockers and cilostazol is low.
      Exercise therapy and smoking cessation need more attention. 

PMID- 25593385
TI  - Design, Synthesis and Evaluation of New 2, 6-Dihydroimidazo[1, 2-c]Pyrimido[5, 4
      e]-Pyrimidine-5(3H)-thiones as Possible Antihistaminic/Antiasthmatic Agents.
AB  - A series of new 10-(alkylamino)-8-methyl-2, 6-dihydroimidazo[1, 2-c]pyrimido[5, 4
      e]pyrimidine-5(3H)-thiones (4a-g) were subjected to molecular property prediction
      (drug-likeness, lipophilicity and solubility parameters) using Osiris Property
      Explorer, ALOGPS 2.1, Molinspiration and ACD/Chemsketch 12.0 software programmes.
      The calculated drug-related properties of the designed molecules were similar to
      those found in most marketed drugs. Amongst the proposed analogues, four
      promising candidates were chosen (4a-d) for synthesis on the basis of Lipinski's
      'Rule of Five' and drug-likeness scores. The significant biological activity of
      the test compounds in two in vitro modes (isolated guinea pig tracheal chain
      preparation, isolated guinea pig ileum) supports the promise and accuracy of the
      prediction. Among them, 4a was the most potent antihistaminic (IC50 value of 30.2
      MUM; standard, chlorpheniramine maleate showed an IC50 of 14.1 MUM). 

PMID- 25593386
TI  - Development and validation of a liquid chromatographic method for estimation of
      dicyclomine hydrochloride, mefenamic Acid and paracetamol in tablets.
AB  - Liquid chromatographic method was developed for simultaneous quantitative
      determination of dicyclomine hydrochloride, mefenamic acid and paracetamol in
      their combined dosage form. The separation was achieved using a C18 column
      (250*4.6 mm id, 5 MUm) using acetonitrile:20 mM potassium dihydrogen phosphate
      70:30 (v/v) adjusted to pH 4 using orthophosphoric acid as mobile phase at a flow
      rate of 1 ml/min and detection at 220 nm. Separation was completed within 12 min.
      The retention times of dicyclomine hydrochloride, mefenamic acid and paracetamol
      were 3.8, 9.3 and 2.5 minutes respectively. The proposed method was found to have
      linearity in concentration range of 10-100 MUg/ml for dicyclomine hydrochloride,
      0.05-10 MUg/ml for mefenamic acid and 0.1-20 MUg/ml for paracetamol. The
      developed method has been statistically validated and was found to be simple,
      precise, reproducible and accurate. The developed and validated method was
      successfully used for the quantitative analysis of commercially available dosage
      form. 

PMID- 25593387
TI  - Development and Validation of Stability-indicating HPLC Method for Simultaneous
      Estimation of Cefixime and Linezolid.
AB  - A stability-indicating reverse phase high performance liquid chromatography
      method was developed and validated for cefixime and linezolid. The wavelength
      selected for quantitation was 276 nm. The method has been validated for
      linearity, accuracy, precision, robustness, limit of detection and limit of
      quantitation. Linearity was observed in the concentration range of 2-12 MUg/ml
      for cefixime and 6-36 MUg/ml for linezolid. For RP-HPLC, the separation was
      achieved by Phenomenex Luna C18 (250*4.6 mm) 5 MUm column using phosphate buffer
      (pH 7):methanol (60:40 v/v) as mobile phase with flow rate 1 ml/min. The
      retention time of cefixime and linezolid were found to be 3.127 min and 11.986
      min, respectively. During force degradation, drug product was exposed to
      hydrolysis (acid and base hydrolysis), H2O2, thermal degradation and photo
      degradation. The % degradation was found to be 10 to 20% for both cefixime and
      linezolid in the given condition. The method specifically estimates both the
      drugs in presence of all the degradants generated during forced degradation
      study. The developed methods were simple, specific and economic, which can be
      used for simultaneous estimation of cefixime and linezolid in tablet dosage form.

PMID- 25593388
TI  - Determination of Ciprofloxacin in Pharmaceutical Formulations Using HPLC Method
      with UV Detection.
AB  - A simple, specific, accurate and rapid reversed phase high performance liquid
      chromatographic method was validated for the determination of the content of
      ciprofloxacin in three pharmaceuticals forms: generic, similar and compounded.
      The results of the validation showed that the method was highly efficient for
      quantification of ciprofloxacin in the matrices evaluated. The recovery rates
      were between 97.4 to 104.3 %, and the relative standard deviations were lower
      than 5 % for repeatability, and lower than 5.15 % for intermediate precision. The
      limits of detection, quantification and practical, were 0.11, 0.35 and 1.56
      MUg/ml, respectively. All compounded samples were approved with in the quality
      control; however, one generic and one similar sample presented above allowed
      level. 

PMID- 25593390
TI  - Antioxidant Activity and Gas Chromatographic-Mass Spectrometric Analysis of
      Extracts of the Marine Algae, Caulerpa peltata and Padina Gymnospora.
AB  - The results of our previous investigations on extracts of selected marine algae
      showed that Caulerpa peltata and Padina gymnospora had more promising
      antiproliferative and antioxidant activities than Gelidiella acerosa and
      Sargassum wightii. Based on these results, the more active chloroform extract of
      C. peltata and ethyl acetate extract of P. gymnospora were further analyzed for
      their constituents by using gas chromatography in tandem with mass spectrometry.
      The GC-MS analysis (GC % peak area given in parentheses) showed that fucosterol
      (12.45%) and L-(+)-ascorbic acid 2, 6-dihexadecanoate (8.13%) were the major
      compounds present in P. gymnospora ethyl acetate extract. On the other hand, C.
      peltata chloroform extract had 1-heptacosanol (10.52%), hexacosanol acetate
      (9.28%), tetradecyl ester of chloroacetic acid (7.22%), Z,Z-6, 28
      heptatriactontadien-2-one (6.77%) and 10, 13-dimethyl-methyl ester of
      tetradecanoic acid (5.34%) as major compounds. Also described in the report are
      the beta-carotene bleaching inhibitory and total reducing activities of the
      chloroform and ethyl acetate extracts of C. peltata and P. gymnospora,
      respectively, relative to the other three extracts (aqueous, methanol, chloroform
      or ethyl acetate) of the two algae. 

PMID- 25593389
TI  - Effect of beta-cyclodextrin on Rheological Properties of some Viscosity
      Modifiers.
AB  - Cyclodextrins are a group of novel excipients, extensively used in the present
      pharmaceutical industry. Sometimes they show significant interactions with other
      conventional additives used in the formulation of dosage forms. The effect of
      beta-cyclodextrin on the rheological properties of aqueous solutions of some
      selected viscosity modifiers was studied in the present work. beta-cyclodextrin
      showed two different types of effects on the rheology of the selected polymers.
      In case of natural polymers like xanthan gum and guar gum, enhanced apparent
      viscosity was found and in case of semi-synthetic polymers like sodium
      carboxymethyl cellulose and methyl cellulose, reduction in apparent viscosity was
      found. beta-cyclodextrin was included at 0.5, 1 and 2% w/v concentrations into
      the polymeric solutions. These findings are useful in the adjustment of
      concentrations of viscosity modifiers during the formulation of physically stable
      disperse systems. 

PMID- 25593391
TI  - Effect of some high consumption spices on hemoglobin glycation.
AB  - Formation of glycation products is major factor responsible in complications of
      diabetes. Worldwide trend is toward the use of natural additives in reducing the
      complications of diseases. Therefore, there is a growing interest in natural
      antiglycation found in plants. Herbs and spices are one of the most important
      targets to search for natural antiglycation from the point of view of safety.
      This study investigated the ability of some of the spices to inhibit glycation
      process in a hemoglobin/glucose model system and compared their potency with each
      other. For this subject the best concentration and time to incubate glucose with
      hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the
      presence of extracts by the three concentrations 0.25, 0.5 and 1 MUg/ml was
      measured colorimetrically at 520 nm. Results represent that some of extracts such
      as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on
      hemoglobin glycation. But some of the extracts such as anise and saffron have not
      only inhibitory effects but also aggravated this event and have proglycation
      properties. In accordance with the results obtained we can conclude that wild
      caraway, turmeric, cardamom and black pepper especially wild caraway extracts are
      potent antiglycation agents, which can be of great value in the preventive
      glycation-associated complications in diabetes. 

PMID- 25593392
TI  - Spectrophotometric estimation of raltegravir potassium in tablets.
AB  - Ultra violet spectrophotometric estimation of the raltegravir potassium, an
      integrase inhibitor antiretroviral agent was estimated by Ultra violet absorption
      maxima method at lambdamax of 328 nm and UV area under curve method in the wave
      length range of 323-333 nm. The Beer's law obeyed in the concentration range of 3
      55 MUg/ml and correlation coefficients were found to be more than 0.996 for both
      methods. The results of the analysis were 100.58+/-0.99 and 99.69+/-0.59 by
      absorption maxima and area under curve method respectively. Both the methods were
      validated as per ICH guidelines. 

PMID- 25593393
TI  - Effects of Cream Containing Ficus carica L. Fruit Extract on Skin Parameters: In
      vivo Evaluation.
AB  - This study was aimed to investigate the effects of cream containing Ficus carica
      L. fruit (Fig) extract on various skin parameters such as skin melanin, erythema,
      moisture content, trans-epidermal water loss and sebum. For this purpose,
      formulation with 4% concentrated extract of F. carica fruit and base without
      extract were developed. Base served as a control. Both base and formulation were
      applied to the cheeks of human volunteers for 8 weeks to investigate the effects
      on different skin parameters using non-invasive bioengineering instruments.
      Formulation decreased the skin melanin, trans-epidermal water loss and skin sebum
      significantly. Formulation increased the skin hydration significantly and
      insignificant effects on skin erythema. We concluded that a stable topical cream
      (w/o emulsion) containing F. carica fruit extract have effects on skin melanin,
      trans-epidermal loss, hydration values and sebum content and possibly could be
      used against for hyper pigmentation, acne, freckles and wrinkle. 

PMID- 25593394
TI  - Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.
AB  - Haloperidol, an antipsychotic drug, leads to the development of a behavioural
      state called catalepsy, in which the animal is not able to correct an externally
      imposed posture. In the present study we have attempted to evaluate the
      anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in
      albino mice. Mice were allocated to four groups, each group containing six
      animals. Both, the test drug, Tribulus terrestris and the standard drug
      trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was
      induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group
      received the vehicle (10 ml/kg, orally), the second group received
      trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus
      terrestris (100, 200 mg/kg, orally). The animals were assessed after single and
      repeated dose administration for ten days, 30 min prior to haloperidol, using
      standard bar test. The result of the present study demonstrates Tribulus
      terrestris has a protective effect against haloperidol-induced catalepsy, which
      is comparable to the standard drug used for the same purpose. Our study indicates
      Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal
      side effects. 

PMID- 25593395
TI  - Flavanone glycosides as acetylcholinesterase inhibitors: computational and
      experimental evidence.
AB  - Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is
      crucially involved in the regulation of neurotransmission. One of the observable
      facts in the neurodegenerative disorders like Alzheimer's disease is the decrease
      in the level of acetylcholine. Available drugs that are used for the treatment of
      Alzheimer's disease are primarily acetylcholinesterase inhibitors with multiple
      activities. They maintain the level of acetylcholine in the brain by inhibiting
      the acetylcholinesterase function. Hence acetylcholinesterase inhibitors can be
      used as lead compounds for the development of drugs against AD. In the present
      study, the binding potential of four flavanone glycosides such as naringin,
      hesperidin, poncirin and sakuranin against acetylcholinesterase was analysed by
      using the method of molecular modeling and docking. The activity of the top
      scored compound, naringin was further investigated by enzyme inhibition studies
      and its inhibitory concentration (IC50) towards acetylcholinesterase was also
      determined. 

PMID- 25593396
TI  - Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum.
AB  - We aimed to study phytochemical screening and analgesic activity of ethanol
      extract of Oroxylum indicum. The dried powder of the barks of the plant was
      extracted with 95% ethanol and was subjected to various phytochemical tests to
      ascertain the principle constituents contained in the extract. The result
      revealed the presence of alkaloids, flavonoids, tannins, glycosides in the
      ethanol extract of Oroxylum indicum. The extract was screened for analgesic
      activity by using hot plate, acetic acid-induced writhing and formalin test. The
      ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed
      significant (P<0.05) analgesic effect in all test methods (hot plate, acetic acid
      induced writhing and formalin). The analgesic activity was compared with a
      standard drug (ketorolac at 10 mg/kg). Based on the present findings and previous
      literature review it can be concluded that flavonoids and tannins might be
      responsible for the analgesic activity. We suggest that ethanol extract of
      Oroxylum indicum might have potential chemical constituents that could be used in
      the future for the development of novel analgesic agent. 

PMID- 25593397
TI  - Adequacy of evidence available to support the claims of efficacy of Ayurvedic
      medicines and treatments.

PMID- 25593398
TI  - The scientific basis of rasa (taste) of a substance as a tool to explore its
      pharmacological behavior.
AB  - BACKGROUND: A rational and well-developed pharmacological basis forms the
      foundation of therapeutics in Ayurveda. The principles and theories of Ayurveda
      need to be validated in the scientific context in order to harness the millennia
      old knowledge. Rasa (taste) of the substance is the foremost tool in Ayurveda to
      assess and determine the pharmacological properties and actions of the substance.
      Similarity in rasa is said to signify similar structure and consequently similar
      pharmacological behavior. Depending on skills developed over the course of long
      term clinical experience one, can register the minute variations in rasa of
      substances and accordingly the possible variations in pharmacological actions.
      Thus, rasa can be used as a scientific tool in the drug discovery process to
      limit and focus the target areas. AIM: To sensitize scientific community to the
      utility of rasa as a tool in the process of drug discovery. MATERIALS AND
      METHODS: All relevant ancient and contemporary literature was reviewed critically
      to form a scientific basis of the Ayurvedic concept of rasa as a tool to identify
      the pharmacological behavior of a substance. CONCLUSION: The review finds that
      rasa (taste) can be used as a guide to identify potential targets in drug
      discovery.

PMID- 25593399
TI  - Evaluation of cytotoxic effects of Anbarnesa on fibroblast L929: Can it be used
      as a mouthwash?
AB  - AIMS: In Iranian traditional medicine Anbarnesa (derived from smoke from burning
      female donkey's stool) has been used to treat ulcers and inflammatory conditions
      like stomatitis and ear infections (otitis). We assess the properties of
      Anbarnesa as an alternative mouthwash. MATERIALS AND METHODS: In this
      experimental study, Anbarnesa smoke was analyzed using aGC-mass device. The smoke
      collected was dissolved at different densities in propylene glycol and incubated
      in Dulbecco's modified Eagle's medium in direct contact with fibroblast cells.
      Assessment of cytotoxicity was done at 1, 24 and 72 h. Cell viability was
      measured by methyl thiazolyl tetrazolium test, and ELISA Reader machine was used
      to read the results. Data were analyzed using one-way ANOVA test. RESULTS: The
      findings of this study showed Anbarnesa was nontoxic in 1/64, 1/128 and 1/256
      dilutions. In 1/32 dilution, toxicity was seen after 72 h. In dilutions, 1/8 and
      1/16 toxicity were seen in the 1(st) h. CONCLUSION: According to the initial
      results of Anbarnesa may be used as an alternative mouthwash with fewer side
      effects for plaque control and prevention of periodontal disease.

PMID- 25593401
TI  - Protective effect of extracts of Baliospermum montanum (Willd.) Muell.-Arg.
      against paracetamol-induced hepatotoxicity-an in vivo and in vitro study.
AB  - AIM: Evaluation of hepatoprotective effect of ethyl methyl ketone and methanol
      sub-fractions obtained from methanol fraction of total methanol extract (ME) was
      carried out both in vivo and in vitro using paracetamol-induced toxicity.
      SETTINGS AND DESIGN: Hepatoprotective activity in vivo was assessed by
      determining the serum levels of glutamic oxaloacetic transaminase (GOT), glutamic
      pyruvic transaminase (GPT), alkaline phosphatase, total bilirubin, total
      cholesterol, total protein (TPTN), and albumin in serum. The studies were
      supported by histopathological examination of liver sections. In vitro activity
      was assessed by determining the change in hepatocyte viability and other
      parameters such as GOT, GPT and TPTN. MATERIALS AND METHODS: The ME of the roots
      of Baliospermum montanum was prepared and fractionated with chloroform and
      methanol to get activity guided fraction. The bio-active guided methanol fraction
      was further fractionated with ethyl methyl ketone and methanol. Both the
      fractions were evaluated for hepatoprotective activity against paracetamol
      induced toxicity. STATISTICAL ANALYSIS: For determining the significant
      intergroup difference each parameter was analyzed separately, and one-way
      analysis of variance was carried out and the individual comparisons of the group
      mean values were done using Dunnet's test. RESULTS: Methanol sub-fraction
      prevented hepatic damage in vivo, induced by paracetamol, whereas both the sub
      fractions showed hepatoprotective effect by restoring altered parameters in the
      selected in vitro model. The results were comparable with the standard
      hepatoprotective drug silymarin. CONCLUSIONS: This study underlines the
      therapeutic potential of B. montanum as per claims in Ayurveda in liver
      disorders.

PMID- 25593400
TI  - Ethanolic extract of Aloe vera ameliorates sciatic nerve ligation induced
      neuropathic pain.
AB  - BACKGROUND: Aloe vera is being used since ages by human kind for treating various
      ailments including various inflammatory conditions, but scientific validation has
      not been done for analgesic activity against neuropathic pain. OBJECTIVE: The
      current study was designed to systematically evaluate the therapeutic potential
      of the ethanolic extract of A. vera (EEAV) against sciatic nerve ligation (SCNL)
      induced neuropathic pain. MATERIALS AND METHODS: Nociceptive threshold of EEAV
      against thermal hyperalgesia, chemical hyperalgesia and mechanical allodynia were
      performed on 0, 7, 14 and 21(st) day post-SCNL. Serum total protein, serum
      nitrite, in vivo anti-oxidant parameters and lipid peroxidation (LPO) were
      estimated. Sciatic nerve homogenate was used to estimate myeloperoxidase (MPO)
      and calcium levels. Histopathology of the sciatic nerve was done to confirm the
      biochemical findings. RESULTS: Treatment with ethanolic extract has increased the
      threshold for the nociception in thermal hyperalgesia, chemical hyperalgesia and
      mechanical allodynia models. A significant improvement of in vivo anti-oxidant
      parameters and decreased LPO levels were observed on treatment with A. vera.
      Significant decrease in serum nitrite, protein, calcium and MPO levels were
      observed, indicating protection against damage caused by SCNL. CONCLUSION: The
      results of the present study validate the use of EEAV to treat neuropathic pain.
      This effect may be attributed to the decreased migration of neutrophils and due
      to the anti-oxidant properties of A. vera. Further studies to confirm the
      mechanism of action will help develop suitable A. vera formulations for
      neuropathic pain therapy.

PMID- 25593402
TI  - Amelioration of oxidative stress by Tabernamontana divaricata on alloxan-induced
      diabetic rats.
AB  - OBJECTIVE: The purpose of this study was to evaluate the anti-diabetic activity
      of ethanol extract of Tabernamontana divaricata (L.) and its ameliorative effect
      on oxidative stress in alloxan-induced diabetic rats. MATERIALS AND METHODS:
      Diabetes was induced by single intraperitoneal injection of alloxan monohydrate
      (140 mg/kg body weight). Methanol extract of T. divaricata was administered at
      the doses of 100 and 200 mg/kg body weight in diabetic induced rats including
      glibenclamide (3 mg/kg) as a reference drug. In the continuous 21 days treatment,
      fasting blood glucose level was determined on 0, 7, 14 and 21 days. On day 21,
      serum lipid profiles and glycosylated hemoglobin, liver antioxidant enzymes
      levels were estimated. RESULTS: Experimental findings showed a significant anti
      diabetic potential of the extract in terms of reduction in blood glucose levels
      and a correct effect on the altered biochemical parameters. Observed data were
      found statistically significant in correction of antioxidant enzyme level
      accompanied with diabetes, particularly at the dose of 200 mg/kg body weight.
      CONCLUSION: Based on the results, it can be concluded that the T. divaricata is
      found to be effective in type 2 diabetes in rats and to have an ameliorative
      effect on the associated oxidative stress.

PMID- 25593403
TI  - Yoga: As an adjunct therapy to trim down the Ayurvedic drug requirement in non
      insulin-dependent diabetes mellitus.
AB  - INTRODUCTION: In spite of a large number of drugs showing anti-hyperglycemic
      activities, none of them have been successful in complete management of diabetes
      mellitus (DM). Yoga and Ayurveda are the two schools of thought in India, which
      have a history of curing diseases since thousands of years. Yogic techniques and
      Ayurvedic herbs have proven their anti-diabetic potential without inducing
      untoward effects. The present study combines Ayurvedic medication with Yoga
      techniques as a new approach toward healing DM. AIMS AND OBJECTIVES: To assess
      the effect of Yoga therapy in the management of non insulin-dependent DM (NIDDM)
      and to decrease the oral drug dose requirement of guduci ghana Tablet. MATERIALS
      AND METHODS: Thirty known NIDDM patients of both genders, who were on guduci
      ghana (solidified aqueous extract of Tinospora cordifolia (Willd.) Miers.)
      tablets from past 2 months as Ayurvedic remedy for DM were selected. Along with
      guduci ghana administration, the subjects were instructed to follow Yogic
      procedures including Asanas, pranayama, and suddhi kriyas. The study was
      conducted for 8 weeks, wherein fasting blood sugar (FBS) and postprandial blood
      sugar (PPBS) levels along with relief in sign and symptoms were assessed at every
      2 weeks intervals, and according to relief in sign and symptoms, tapering of drug
      dosage was carried out. The obtained data were analyzed statistically by applying
      paired t-test. RESULTS AND CONCLUSION: The results obtained were promising as the
      relief in diabetic symptomatology was highly significant in terms of P value.
      80.83% reduction in dose of guduci ghana tablets and 7.85% and 8.78% fall in FBS
      and PPBS levels, respectively, after the complete course of treatment. The
      obtained P value showed highly significant results.

PMID- 25593404
TI  - A clinical trial for evaluation of leech application in the management of
      Vicarcika (Eczema).
AB  - BACKGROUND: Skin diseases are among the most common health problems worldwide and
      are associated with a considerable burden. Eczema is such a skin ailment which
      cause psychological, social and financial burden on the patient and their
      families. Management of eczema with antibiotics, antihistamines, steroids etc.,
      are available but even after their use relapses, recurrences and other
      complications are very common. AIM: The aim of this study was to assess the
      efficacy of leech application in the management of vicarcika (Eczema) with
      standard clinical parameters viz. Eczema Area and Severity Index (EASI) score,
      SCORing of Atopic Dermatitis (SCORAD) Index and Dermatology Life Quality Index
      (DLQI). MATERIALS AND METHODS: An open labeled clinical trial study without
      control group was conducted with 27 patients having the classical symptoms of
      vicarcika (Eczema), selected as per the inclusion and exclusion criteria from
      outpatient department and inpatient department sections of Shalya Department,
      S.V. Ayurvedic Hospital, Tirupati. Minimum four sittings of leech application
      were carried out with 7 days interval. Pre- and post-treatment evaluation of the
      patient was done with Eczema Area and Severity Index (EASI) score, SCORing of
      Atopic Dermatitis (SCORAD) Index and Dermatology Life Quality Index (DLQI).
      STATISTICAL ANALYSIS: Analysis of the data was done with Student's paired t-test.
      RESULTS: The total EASI score showed considerable reduction up to 54.45% (P <
      0.01) and the SCORAD Index significantly reduced by 55% (P < 0.01). The life
      quality of the patient calculated by DLQI improved significantly by 62.36% (P <
      0.01). CONCLUSION: Leech application gives significant relief for the symptoms of
      eczema. The life quality of the patient also improved significantly after leech
      therapy. No adverse reactions were reported during the entire course of study.

PMID- 25593405
TI  - The effect of Macrotyloma uniflorum seed on bile lithogenicity against diet
      induced cholelithiasis on mice.
AB  - BACKGROUND: The seeds of Macrotyloma uniflorum Lam. (Family Fabaceae) contain
      extractable total and tannins with reported hepatoprotective, hypocholesterolemic
      and antioxidant activity. In this study, dietary M. uniflorum seed, methanolic
      and acetone extracts (ME and AE) were examined for their bile-antilithogenic
      potential. MATERIALS AND METHODS: Mice fed with 1% cholesterol and 0.5% cholic
      acid lithogenic (LG) diet for 8 weeks resulted in cholesterol super saturation in
      gallbladder bile, which promotes the formation of cholesterol gallstones (CGSs).
      RESULTS: AE reduced the CGS incidence by 60.21%, and serum total cholesterol,
      triglyceride (TG), very low density lipoprotein (LDL) and LDL compared to control
      animals. Seed extracts at 300 mg/kg dose markedly reduced biliary cholesterol
      (BC) and decreased bile salt content. The ratio of BC to phospholipid which was
      2.64 in the LG diet group was reduced to 1.57-1.35 in the M. uniflorum seed
      extracts treated groups. Liver cholesterol and TG were decreased significantly by
      feeding of ME and AE at 300 mg/kg dose. AE significantly reversed the changes in
      apolipoproteins A-I and C-II level disturbed by LG diet. CONCLUSIONS: M.
      uniflorum seed exerted antilithogenic influence by decreasing the cholesterol
      hyper-secretion into bile and increasing the bile acid output, thus decreasing
      the formation of LG bile in mice. The effect was maximum in the AE as it also
      reduced papillary proliferation of gallbladder and fatty degeneration of the
      liver. The potential antilithogenic effect of the AE of M. uniflorum may be due
      to antioxidant property of its rich total polyphenol and tannins content.

PMID- 25593406
TI  - Gastroprotective effect of aqueous extract and mucilage from Bryophyllum pinnatum
      (Lam.) Kurz.
AB  - CONTEXT: Bryophyllum pinnatum is used as traditional medicine in India, Africa,
      Tropical America and China for treatment of various diseases. B. pinnatum
      contains different groups of phytoconstituents viz., flavonoid, terpenoids,
      alkaloid, phenolic compounds. AIM: The present study was carried out to evaluate
      the gastroprotective activity of B. pinnatum whole plant aqueous extract, and
      mucilage (MUC) isolated from the whole plant against ethanol induced gastric
      ulcer. MATERIALS AND METHODS: Pretreatment of rats with aqueous extract at dose
      level of 500 and 750 mg/kg b.w., MUC at 500 mg/kg dose level and standard drug
      Rabeprazole at dose level of 20 mg/kg b.w. where given for 7 days. RESULTS: The
      aqueous whole plant extract of B. pinnatum at dose of 750 mg/kg p.o. and MUC at
      dose of 500 mg/kg p.o. markedly decrease the incidence of ulcers in ethanol
      induced ulcer rats. In ethanol induced ulcer rats, there was a decrease in the
      gastric volume, free and total acidity and ulcerative index as compared to the
      control group. Total carbohydrate content was found to be an increase as compare
      to control the group. The aqueous whole plant extract of B. pinnatum at dose of
      750 mg/kg showed a significant reduction in the above parameters which was
      comparable to the standard drug rabeprazole (20 mg/kg). B. pinnatum extract and
      MUC showed protection index 72.69 and 69.65% respectively, whereas standard drug
      rabeprazole showed protection index 75.49%. CONCLUSIONS: Whole plant extracts of
      B. pinnatum and MUC has potent gastroprotective effect which can be further
      clinically studied for new drug development.

PMID- 25593408
TI  - IN SEARCH OF GENDER NEUTRALITY: Is Singular They a Cognitively Efficient
      Substitute for Generic He?
AB  - With increasing frequency, writers and speakers are ignoring grammatical
      proscription and using the plural pronoun they to refer to singular antecedents.
      This change may, in part, be motivated by efforts to make language more gender
      inclusive. In the current study, two reading-time experiments demonstrated that
      singular they is a cognitively efficient substitute for generic he or she,
      particularly when the antecedent is nonreferential. In such instances, clauses
      containing they were read (a) much more quickly than clauses containing a
      gendered pronoun that went against the gender stereotype of the antecedent, and
      (b) just as quickly as clauses containing a gendered pronoun that matched the
      stereotype of the antecedent. However, with referential antecedents, for which
      the gender was presumably known, clauses containing singular they were not read
      as quickly as clauses containing a gendered pronoun that matched the antecedent's
      stereotypic gender.

PMID- 25593407
TI  - The Activation of Embedded Words in Spoken Word Recognition.
AB  - The current study investigated how listeners understand English words that have
      shorter words embedded in them. A series of auditory-auditory priming experiments
      assessed the activation of six types of embedded words (2 embedded positions * 3
      embedded proportions) under different listening conditions. Facilitation of
      lexical decision responses to targets (e.g., pig) associated with words embedded
      in primes (e.g., hamster) indexed activation of the embedded words (e.g., ham).
      When the listening conditions were optimal, isolated embedded words (e.g., ham)
      primed their targets in all six conditions (Experiment 1a). Within carrier words
      (e.g., hamster), the same set of embedded words produced priming only when they
      were at the beginning or comprised a large proportion of the carrier word
      (Experiment 1b). When the listening conditions were made suboptimal by expanding
      or compressing the primes, significant priming was found for isolated embedded
      words (Experiment 2a), but no priming was produced when the carrier words were
      compressed/expanded (Experiment 2b). Similarly, priming was eliminated when the
      carrier words were presented with one segment replaced by noise (Experiment 3).
      When cognitive load was imposed, priming for embedded words was again found when
      they were presented in isolation (Experiment 4a), but not when they were embedded
      in the carrier words (Experiment 4b). The results suggest that both embedded
      position and proportion play important roles in the activation of embedded words,
      but that such activation only occurs under unusually good listening conditions.

PMID- 25593409
TI  - Clinical photography and our responsibilities.

PMID- 25593410
TI  - Farewell readers.

PMID- 25593411
TI  - Bernard McCarthy O'Brien: The champ who was determined to excel.

PMID- 25593412
TI  - Hypertelorism.
AB  - The term orbital hypertelorism (ORH) implies "widely apart orbits." This may also
      be associated with the abnormal vertical orientation of the orbits (dystopia).
      This deformity may be unilateral or bilateral, symmetric or asymmetric and may be
      present in a variety of craniofacial conditions. The treatment is primarily
      carried out for aesthetic reasons. The timing of treatment is dictated by the
      underlying condition and the type of procedure envisaged. The mainstay of
      treatment consists of moving the orbits medially to near normal position. This is
      accomplished by either an orbital translocation or facial bipartition technique.
      The choice of procedure is governed by the shape of the maxillary arch and
      associated occlusal conditions. We must differentiate between the telecanthus
      (also called pseudo-hypertelorism) and a true ORH as the management differs in
      these two conditions. The ORH involves extensive intracranial and extracranial
      operation whereas the telecanthus correction is relatively simpler surgery. The
      article will discuss the aetiology, classification, presentation, treatment
      options, timing of surgery and the choice of surgical procedures. Illustrative
      case reports with long-term results will be used to explain the management of
      these patients. 

PMID- 25593413
TI  - Current status of presurgical infant orthopaedic treatment for cleft lip and
      palate patients: A critical review.
AB  - Rehabilitation of cleft lip and palate (CLP) patients is a challenge for all the
      concerned members of the cleft team, and various treatment modalities have been
      attempted to obtain aesthetic results. Presurgical infant orthopaedics (PSIO) was
      introduced to reshape alveolar and nasal segments prior to surgical repair of
      cleft lip. However, literature reports lot of controversy regarding the use of
      PSIO in patients with CLP. Evaluation of long-term results of PSIO can provide
      scientific evidence on the efficacy and usefulness of PSIO in CLP patients. The
      aim was to assess the scientific evidence on the efficiency of PSIO appliances in
      patients with CLP and to critically analyse the current status of PSIO. A PubMed
      search was performed using the terms PSIO, presurgical nasoalveolar moulding and
      its long-term results and related articles were selected for the review. The
      documented studies report no beneficial effect of PSIO on maxillary arch
      dimensions, facial aesthetics and in the subsequent development of dentition and
      occlusion in CLP patients. Nasal moulding seems to be more beneficial and
      effective in unilateral cleft lip and palate patients with better long-term
      results. 

PMID- 25593414
TI  - Cutaneous wound healing: Current concepts and advances in wound care.
AB  - A non-healing wound is defined as showing no measurable signs of healing for at
      least 30 consecutive treatments with standard wound care.[1] It is a snapshot of
      a patient's total health as well as the ongoing battle between noxious factors
      and the restoration of optimal macro and micro circulation, oxygenation and
      nutrition. In practice, standard therapies for non-healing cutaneous wounds
      include application of appropriate dressings, periodic debridement and
      eliminating causative factors.[2] The vast majority of wounds would heal by such
      approach with variable degrees of residual morbidity, disability and even
      mortality. Globally, beyond the above therapies, newer tools of healing are
      selectively accessible to caregivers, for various logistical or financial
      reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT), as
      used at our institution (CAMC), and some other modalities that are relatively
      accessible to patients. HBOT is a relatively safe and technologically simpler way
      to deliver care worldwide. However, the expense for including HBOT as standard of
      care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society)
      may vary widely from country to country and payment system.[3] In the USA, CMS
      (Centers for Medicare and Medicaid Services) approved indications for HBOT vary
      from that of the UHMS for logistical reasons.[1] We shall also briefly look into
      other newer therapies per current clinical usage and general acceptance by the
      medical community. Admittedly, there would be other novel tools with variable
      success in wound healing worldwide, but it would be difficult to include all in
      this treatise. 

PMID- 25593415
TI  - Evaluation of lymphangiogenesis in acellular dermal matrix.
AB  - INTRODUCTION: Much attention has been directed towards understanding the
      phenomena of angiogenesis and lymphangiogenesis in wound healing. Thanks to the
      manifold dermal substitute available nowadays, wound treatment has improved
      greatly. Many studies have been published about angiogenesis and cell invasion in
      INTEGRA((r)). On the other hand, the development of the lymphatic network in
      acellular dermal matrix (ADM) is a more obscure matter. In this article, we aim
      to characterize the different phases of host cell invasion in ADM. Special
      attention was given to lymphangiogenic aspects. MATERIALS AND METHODS: Among 57
      rats selected to analyse the role of ADM in lymphangiogenesis, we created four
      groups. We performed an excision procedure on both thighs of these rats: On the
      left one we did not perform any action except repairing the borders of the wound;
      while on the right one we used INTEGRA((r)) implant. The excision biopsy was
      performed at four different times: First group after 7 days, second after 14
      days, third after 21 days and fourth after 28 days. For our microscopic
      evaluation, we used the classical staining technique of haematoxylin and eosin
      and a semi-quantitative method in order to evaluate cellularity counts. To assess
      angiogenesis and lymphangiogenesis development we employed PROX-1 Ab and
      CD31/PECAM for immunohistochemical analysis. RESULTS: We found remarkable wound
      contraction in defects that healed by secondary intention while minor wound
      contraction was observed in defects treated with ADM. At day 7, optical
      microscopy revealed a more plentiful cellularity in the granulation tissue
      compared with the dermal regeneration matrix. The immunohistochemical process
      highlighted vascular and lymphatic cells in both groups. After 14 days a high
      grade of fibrosis was noticeable in the non-treated group. At day 21, both
      lymphatic and vascular endothelial cells were better developed in the group with
      a dermal matrix application. At day 28, lymphatic endothelial cells had organized
      themselves, engineering the pseudocylindrical structure better disposed in the
      ADM group than in the control group, and the lymphatic cells were detectable
      inside the vessels' lumen in this group. CONCLUSION: This study has made it
      possible to demonstrate the absolute importance of an ADM in proper wound healing
      and has shown better definition of both the qualitative and quantitative aspects
      of lymphangiogenesis compared to the second intention healing. A major grade of
      organization of the extracellular matrix and a minor grade of fibrosclerosis in
      ADM allowed a well-structured morphologic and functional development of the
      endothelial and lymphatic vascular structures. This study hopes to represent a
      clinical basis for a wider use of ADM in lesions where lymphatic complications
      are common.

PMID- 25593416
TI  - Enhancing dermal and bone regeneration in calvarial defect surgery.
AB  - INTRODUCTION: To optimize the functional and esthetic result of cranioplasty, it
      is necessary to choose appropriate materials and take steps to preserve and
      support tissue vitality. As far as materials are concerned, custom-made porous
      hydroxyapatite implants are biomimetic, and therefore, provide good biological
      interaction and biointegration. However, before it is fully integrated, this
      material has relatively low mechanical resistance. Therefore, to reduce the risk
      of postoperative implant fracture, it would be desirable to accelerate
      regeneration of the tissues around and within the graft. OBJECTIVES: The
      objective was to determine whether integrating growth-factor-rich platelet gel or
      supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate
      bone remodeling and promote soft tissue regeneration, respectively. MATERIALS AND
      METHODS: The investigation was performed on cranioplasty patients fitted with
      hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet
      gel was applied to the bone/prosthesis interface during surgery, and in a further
      5 patients, characterized by thin, hypotrophic skin coverage of the cranial
      lacuna, a sheet of dermal matrix was applied between the prosthesis and the
      overlying soft tissue. In several of the former groups, platelet gel mixed with
      hydroxyapatite granules was used to fill small gaps between the skull and the
      implant. To confirm osteointegration, cranial computed tomography (CT) scans were
      taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI) was
      used to confirm dermal integrity. RESULTS: Clinical examination performed a few
      weeks after surgery revealed good dermal regeneration, with thicker, healthier
      skin, apparently with a better blood supply, which was confirmed by MRI at 3-6
      months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous
      hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite
      granules were used to fill gaps between the implant and skull appeared to show
      more rapid integration of the implant than untreated areas. Results were stable
      at 1-year and remain so to date in cases where follow-up is still ongoing.
      CONCLUSIONS: Bone remodeling time could be reduced by platelet gel application
      during cranioplasty with porous hydroxyapatite implants. Likewise, layering
      dermal matrix over such implants appears to promote dermal tissue regeneration
      and the oshtemo mimetic process. Both of these strategies may, therefore, reduce
      the likelihood of postsurgical fracture by promoting mechanical resistance.

PMID- 25593417
TI  - Securing aesthetic outcomes for composite grafts to alar margin and columellar
      defects: A long term experience.
AB  - INTRODUCTION: Composite grafts for nasal reconstruction have been around for over
      a century but the opinion on its virtues and failings keeps vacillating with a
      huge difference on the safe size of the graft for transfer. Alar margin and
      columellar defects are more distinct than dorsal nasal defects in greater
      difficulty in ensuring a good aesthetic outcome. We report our series of 19
      consecutive patients in whom a composite graft was used to reconstruct a defect
      of alar margin (8 patients), alar base (7 patients) or columella (4 patients).
      PATIENTS AND METHODS: Patient ages ranged from 3-35 years with 5 males and 14
      females. The grafts to alar margin and base ranged 0.6-1 cm in width, while
      grafts to columella were 0.7-1.2 cm. The maximum dimension of the graft in this
      series was 0.9 mm x 10 mm. Composite grafts were sculpted to be two layered (skin
      + cartilage), three layered wedges (skin + cartilage + skin) or their combination
      (two layered in a portion and three layered in another portion). All grafts were
      cooled in postoperative period for three days by applying an indigenous ice pack
      of surgical glove. The follow up ranged from 3-9 months with an average of 4.5
      months. RESULTS: All of our 19 composite grafts survived completely but they all
      shrank by a small percentage of their bulk. Eleven patients rated the outcome
      between 90-95% improvement. We noticed that composite grafts tended to show
      varied pigmentation in our patients, akin to split skin grafts. CONCLUSION: In
      our opinion, most critical to graft survival is its size and the ratio of the
      marginal raw area to the graft bulk. We recommend that graft width should not
      exceed 1 cm to ensure complete survival even though larger sized grafts have been
      reported to survive. We recommend cooling of the graft and justify it on the
      analogy of 'warm ischemia time' for a replantation, especially in warmer climes
      like ours in India. We have outlined several considerations in the technique,
      with an analysis of differing opinions that should facilitate a surgeon in making
      an informed choice.

PMID- 25593418
TI  - Options for the nasal repair of non-syndromic unilateral Tessier no. 2 and 3
      facial clefts.
AB  - BACKGROUND: Non-syndromic Tessier no. 2 and 3 facial clefts primarily affect the
      nasal complex. The anatomy of such clefts is such that the ala of the nose has a
      cleft. Repairing the ala presents some challenges to the surgeon, especially to
      correct the shape and missing tissue. Various techniques have been considered to
      repair these cleft defects. AIM: We present two surgical options to repair such
      facial clefts. MATERIALS AND METHODS: A nasal dorsum rotational flap was used to
      treat patients with Tessier no. 2 clefts. This is a local flap that uses tissue
      from the dorsal surface of the nose. The advantage of this flap design is that it
      helps move the displaced ala of a Tessier no. 2 cleft into its normal position. A
      forehead-eyelid-nasal transposition flap design was used to treat patients with
      Tessier no. 3 clefts. This flap design includes three prongs that are rotated
      downward. A forehead flap is rotated into the area above the eyelid, the flap
      from above the eyelid is rotated to infra-orbital area and the flap from the
      infraorbital area that includes the free nasal ala of the cleft is rotated into
      place. RESULTS AND CONCLUSIONS: These two flap designs show good results and can
      be used to augment the treatment options for repairing Tessier no. 2 and 3 facial
      clefts.

PMID- 25593419
TI  - Cephalometric evaluation of the pharyngeal airway space after orthognathic
      surgery and distraction osteogenesis of the jaw bones.
AB  - OBJECTIVE: Orthognathic surgeries and distraction osteogenesis (DO) of the jaw
      bones cause a change in the pharyngeal airway space (PAS). The aim of our study
      was to evaluate the magnitude of changes occurring in the pharyngeal airway after
      mandibular set-back surgeries and DO of maxilla/mandible. MATERIALS AND METHODS:
      The study undertaken was a retrospective cephalometric study. Subjects included
      in our study had undergone mandibular set-back surgery or DO of maxilla/mandible.
      Lateral cephalograms of the subjects taken pre-operatively (T0), immediate post
      operatively (T1) and after a minimum follow-up period of 6 months (T2) were
      studied. The cephalograms were traced manually and the following parameters were
      evaluated: Surface area of the PAS, pharyngeal airway width at the level of the
      base of the tongue, position of the hyoid bone and the tongue. Repeated measure
      ANOVA test was done to assess the presence of any significant changes in the
      proposed parameters at T0, T1 and T2. A correlation analysis was made between the
      mandibular/maxillary movements and the corresponding changes in the PAS. RESULTS:
      Surgical movements of maxilla and mandible do have an effect on the pharyngeal
      airway. CONCLUSION: It was clearly evident that the effects of mandibular
      movements on the PAS and the hyoid bone is more significant than the maxillary
      movements.

PMID- 25593420
TI  - Transoral versus extraoral approach for mandibular angle fractures: A comparative
      study.
AB  - INTRODUCTION: Mandibular fractures represent approximately two-thirds of all the
      maxillofacial fractures (nearly 70%) out of which fractures of mandibular angle
      represent for 26-35%. AIM OF THE STUDY: The aim of this study is to compare the
      transoral and extraoral (submandibular) approaches for fixation of mandibular
      angle fractures. OBJECTIVES OF STUDY: The objectives of the following study are
      to evaluate ease of accessibility, time taken for the procedure, ease of anatomic
      reduction and complications. MATERIALS AND METHODS: A prospective study was
      carried out in 30 patients reporting to the Department of Oral and Maxillofacial
      surgery, Narayana Dental College and Hospital, Nellore, Andhra Pradesh during the
      period of months from November 2011 to August 2013 who were randomly divided in
      two groups based on computer generated simple randomization chart. Group I
      patients underwent transoral reduction and fixation and Group II patients
      underwent extraoral reduction and fixation. The ease of accessibility was
      analysed by visual analogue scale by the operating surgeon, time taken from
      incision to closure with digital clock, difficulty level index of surgeon based
      on the time taken for the procedure and approach related complications. RESULTS:
      The ease of accessibility in Group I was good in 53.3% while in Group II patients
      approached extraorally it was good in 86.7%. Group I patients approached
      transorally showed a mean of 49.7 min while that of Group II patients approached
      extraorally showed a mean of 73.4 min. Group I had a minimum difficulty level
      index in 60%, moderate difficulty level in 33.3% and severe difficulty level in
      6.7% while Group II had a minimum and moderate difficulty level in 46.7% and
      severe difficulty level in 6.7%. There was 1 (6.7%) complication reported in each
      group. CONCLUSION: The statistical analysis of this study concludes that fracture
      line starting anterior to mandibular third molar and ending at anteroinferior
      border of the insertion of the masseter muscle or posterior body of mandible can
      be approached transorally. Fracture line starting posterior or distal to the
      third molar or posterior to the insertion of the masseter muscle to the angle of
      the mandible or fracture line extending high in the ramus, extraoral approach
      provides a better choice for reduction and fixation of the fractured segments
      with restoration of anatomical and functional occlusion.

PMID- 25593421
TI  - Prospective long-term study of patency and outcomes of 505 arteriovenous fistulas
      in patients with chronic renal failure: Authors experience and review of
      literature.
AB  - BACKGROUND: This study describes our experience of arteriovenous fistula (AVF)
      creation as vascular access for haemodialysis. MATERIALS AND METHODS: This study
      has been carried out in our hospital from January 2004 to December 2012. A total
      of 505 AVFs were created in 443 patients. Maximum follow-up was 8 years, and
      minimum was 6 months. OBSERVATIONS AND RESULTS: In this study of 505 cases of
      AVFs, primary patency rates by Kaplan - Meier analysis showed 78.81% patency of
      fistulas at the end of 1 year and patency dropped to 14.81% at the end of 5
      years. Our primary failure rate was 21.2%. Basilic vein was used in 26.35% cases,
      cephalic vein in 63.5%, and antecubital vein in 9.75% cases. On table, bruit was
      present in 459 (90.9%) and thrill in 451 (89.3%) cases. During dialysis, flow
      rate >250 ml/min was obtained in 150 (29.9%) cases. In complications, 2 (0.4%)
      patients developed distal oedema, 33 (6.5%) developed steal phenomenon.
      CONCLUSIONS: Presence of on table thrill and bruit are indicators of successful
      AVF. If vein diameter is <2 mm, chances of AVF failure are high. Flow rates in
      patients with vein diam. >2 mm were significantly higher as compared with
      patients with vein diam. <2 mm (P < 0.001). Flow rates are higher in non-diabetic
      patients as compared to diabetic patients (P < 0.001). Average blood urea and
      serum creatinine values are significantly lesser in patients undergoing dialysis
      through successful fistulas as compared to patients with failed fistulas.
      Correspondingly, incidence of deaths is significantly lesser in patients with
      successful fistulas. During proximal side-to-side fistula between
      antecubital/basilic vein and brachial artery, dilating of the first valve toward
      wrist helps to develop distal veins in the forearm by retrograde flow. This
      technique avoids requirement of superficialization of basilic vein in the arm.

PMID- 25593422
TI  - Effect of green tea on the second degree burn wounds in rats.
AB  - BACKGROUND: Various studies indicate that the green tea has anti-inflammatory and
      anti-oxidative properties. Moreover, a few studies have been carried out that
      demonstrate beneficial effects of green tea on burned patients. MATERIALS AND
      METHODS: In this study, green tea, Vaseline, and silver sulfadiazine dressings
      were used as first-aid treatment to deep dermal contact burns in rats, compared
      with a control of nothing. After creating second-degree burn on the dorsum of
      rats, the treatments were applied for 15 min in four groups. Wound dressing
      changes were daily. Macroscopic study was performed on days 1, 3, 7, and 14 by
      using a digital camera and software processing of photos. Microscopic examination
      was done by pathologic evaluation of skin specimens on day 14. RESULTS: We
      observed that green tea usage significantly decreased burn size in comparison to
      the control group (P = 0.004). CONCLUSION: Green tea is effective on healing
      process of second degree burn wounds.

PMID- 25593423
TI  - Post-burn axillary contracture: A therapeutic challenge!
AB  - BACKGROUND: Axillary post-burn scar contracture is a challenging problem to the
      reconstructive surgeon owing to the wide range of abduction that should be
      achieved. The aim of this paper was to highlight the various options used in
      managing axillary contractures in our hospital. MATERIALS AND METHODS: This is a
      retrospective hospital-based study of axillary contractures managed at Safdarjung
      Hospital (a tertiary care hospital) from 2009 to 2013. The study consisted of 44
      patients from all age group and both sex included in it. Patients with a
      bilateral axillary contracture were excluded. Axillary contracture was released
      and resurfaced using split skin graft and/or with different types of flaps
      including the propeller flap, parascapular flap. All the reconstructed cases were
      followed-up for a period of 12 months. Assessment was done on the basis of
      functional and aesthetic outcome. RESULTS: Forty-four patients consisting of 25
      males and 19 females presented with axillary contractures that involved 44
      axillae. The mean age of the study group was 17.1 years. Injuries involved the
      anterior axillary fold in 8 (18.18%), posterior fold in ten (22.72%), both folds
      and axillary fossa in 14 (31.81%) and both folds plus part of the chest wall and
      arm (sparing the axillary fossa) in 12 (27.27%) axillae. Surgical treatment
      included split-thickness skin graft in 15 (34.1%), local skin flaps in 4 (9.1%),
      Z-plasties in 4 (9.1%), parascapular flaps in 3 (6.82%), while propeller flaps in
      12 (27.27%) and square flap were used in 6 (13.64%) patients. The percentage of
      improvement in abduction had a mean of 156 degrees . The functional and aesthetic
      results were satisfactory. CONCLUSION: The choice of surgical procedure for
      reconstruction of post-burn axillary contractures can be made according to the
      pattern of scar contracture and the state of the surrounding skin. The choice of
      a flap should have priority over the skin graft because of the superior
      functional and aesthetic results of flaps.

PMID- 25593424
TI  - Effect of intense pulsed light on immature burn scars: A clinical study.
AB  - INTRODUCTION: As intense pulsed light (IPL) is widely used to treat cutaneous
      vascular malformations and also used as non-ablative skin rejunuvation to remodel
      the skin collagen. A study has been undertaken to gauze the effect of IPL on
      immature burn scars with regard to vascularity, pliability and height. MATERIALS
      AND METHODS: This study was conducted between June 2013 and May 2014, among
      patients with immature burn scars that healed conservatively within 2 months.
      Photographic evidence of appearance of scars and grading and rating was done with
      Vancouver Scar Scale parameters. Ratings were done for both case and control scar
      after the completion of four IPL treatment sessions and were compared. RESULTS:
      Out of the 19 cases, vascularity, pliability and height improved significantly (P
      < 0.05) in 13, 14 and 11 scars respectively following IPL treatment. CONCLUSIONS:
      Intense pulsed light was well-tolerated by patients, caused good improvement in
      terms of vascularity, pliability, and height of immature burn scar.

PMID- 25593425
TI  - Electrolyte and Haemogram changes post large volume liposuction comparing two
      different tumescent solutions.
AB  - BACKGROUND: The most common definitions of large volume liposuction refer to
      total 5 l volume aspiration during a single procedure (fat plus wetting
      solution). Profound haemodynamic and metabolic alterations can accompany large
      volume liposuction. Due to paucity of literature on the effect of different
      tumescent solutions on the electrolyte balance and haematological changes during
      large volume liposuction, we carried out this study using two different wetting
      solutions to study the same. MATERIALS AND METHODS: Total 30 patients presenting
      with varying degrees of localized lipodystrophy in different body regions were
      enrolled for the study. Prospective randomized controlled trial was conducted by
      Department of Plastic and Cosmetic Surgery, Sir Ganga Ram Hospital, New Delhi
      from January 2011 to June 2012. Patients were randomized into two groups of 15
      patients each by using computer generated random numbers. Tumescent formula used
      for Group A (normal saline [NS]) was our modification of Klein's Formula and
      Tumescent formula used for Group B (ringer lactate [RL]) was our modification of
      Hunstadt's formula. Serum electrolytes and hematocrit levels were done at
      preinduction, immediate postoperative period and postoperative day 1. RESULT:
      Statistical analysis was performed using SPSS software version 15.0. Which showed
      statistically significant electrolytes and hematocrit changes occur during large
      volume liposuction. CONCLUSION: Statistically significant electrolytes and
      hematocrit changes occur during large volume liposuction and patients should be
      kept under observation of anaesthesist for at least 24 h. Patients require strict
      monitoring of vital parameters and usually Intensive Care Unit is not required.
      There was no statistical difference in the electrolyte changes using NS or RL as
      tumescent solution and both solutions were found safe for large volume
      liposuction.

PMID- 25593427
TI  - The efficacy of VAC therapy on chemotherapeutic extravasation ulcers: An
      experimental study.

PMID- 25593426
TI  - The efficacy of negative pressure wound therapy on chemotherapeutic extravasation
      ulcers: An experimental study.
AB  - CONTEXT: The extravasation of the chemotherapeutic agents is not an unusual
      phenomenon. Necrosis of the skin and underlying structures has been reported,
      depending on the cytotoxicity of the extravasating drug. Despite the presence of
      some antidotes, such wounds tend to enlarge with time and are likely to resist
      the treatment. AIMS: The objective of this study was to investigate the efficacy
      of negative pressure wound therapy (NPWT) on extravasation ulcers. SETTINGS AND
      DESIGN: Animals were separated into two groups; conventional dressing group and
      NPWT group. MATERIALS AND METHODS: Extravasation necrosis was established by
      intradermal doxorubicin injection. Following the debridement of the necrotic
      areas, one group of animals was treated with the conventional dressing while NPWT
      was applied to the other group. The wound areas were measured, and then biopsies
      were taken on the 3(rd), 7(th) and 14(th) days after the debridement. STATISTICAL
      ANALYSIS USED: SPSS 11.5 for Windows was used. Two-way ANOVA test was used to
      compare wound areas between groups. Willcoxon sign test with Bonferroni
      correction was used to compare histological scores between groups. Chi-square
      test with Bonferroni correction was used to compare histological scores within
      the group between the days. RESULTS: There is no significant difference in terms
      of inflammatory cell count, neovascularisation, granulation tissue formation
      between the groups. Contrary to these results wound areas at the end of the
      treatment were smaller in the NPWT group compared with the dressing group.
      CONCLUSION: There is the superiority of NPWT over conventional dressing in
      chemotherapeutic extravasation wounds as well as the wound area is concerned, but
      it is not proven histologically.

PMID- 25593428
TI  - Karydakis procedure for sacrococcygeal pilonidal sinus disease: Our experience.
AB  - AIM: The purpose of this study was to evaluate patients with sacrococcygeal
      pilonidal sinus disease (SPSD) who underwent Karydakis procedure at our centre
      with reference to the perioperative findings, early and late postoperative
      results and recurrence. MATERIALS AND METHODS: A total of 103 patients presenting
      with SPSD at our centre underwent Karydakis flap repair from January 2001 to
      December 2010. These patients were then followed-up and evaluated with respect to
      operative time, drain use, hospital stay, suture removal, complications, and
      recurrence. RESULTS: The mean operative time was 74.9 min with a median hospital
      stay of 5 days. Drains were removed at a median of 7 days and sutures at a median
      of 15 days. Twenty-one patients presented with serous collection in the wound.
      Six patients had wound infection. Patients were followed-up for a median of 29
      months. No recurrences were noted in any of the cases. CONCLUSION: Karydakis flap
      procedure is a relatively simple procedure for SPSD with reproducible low
      recurrence rates.

PMID- 25593429
TI  - Beyond antisepsis: Examining the relevance of the works of Joseph Baron Lister to
      the contemporary surgeon-scientist.
AB  - As the father of antispesis, the legacy of Joseph Baron Lister is assured and his
      influence on the development of contemporary surgical practice is recognised in
      the context of his achievement of predictable, infection-free surgery. However,
      looking beyond Lister's finest achievement and examining this work in the context
      of his whole career as a surgeon-scientist reveals important lessons pertinent to
      aspiring peers in how, by replacing surgical dogma with observation, deductive
      reasoning and scientific verification, by pursuing good ideas in the face of
      resistance and by making research directly relevant and patient-focused, lasting
      changes can be accomplished. This short paper aims to put Lister's developments
      in antisepsis in the context of his whole career, to evaluate his legacy and to
      commend his approach to contemporary surgeon-scientists. 

PMID- 25593430
TI  - Timer switch to convert suction apparatus for negative pressure wound therapy
      application.
AB  - BACKGROUND: Negative pressure wound therapy (NPWT) is an established modality in
      the treatment of chronic wounds, open fractures, and post-operative wound
      problems. This method has not been widely used due to the high cost of equipment
      and consumables. This study demonstrates an indigenously developed apparatus
      which gives comparable results at a fraction of the cost. Readily available
      materials are used for the air-tight dressing. MATERIALS AND METHODS: Equipment
      consists of suction apparatus with adjustable pressure valve set to a pressure
      125-150 mmHg. An electronic timer switch with a sequential working time of 5 min
      and a standby time of 3 min provides the required intermittent negative pressure.
      Readily available materials such as polyvinyl alcohol sponge, suction drains and
      steridrapes were used to provide an air tight wound cover. RESULTS: A total of 90
      cases underwent 262 NPWT applications from 2009 to 2014. This series, comprised
      of 30 open fractures, 21 post-operative and 39 chronic wounds. The wound healing
      rate in our study was comparable to other published studies using NPWT.
      CONCLUSION: The addition of electronic timer switch will convert a suction
      apparatus into NPWT machine, and the results are equally effective compared to
      more expensive counter parts. The use of indigenous dressing materials reduces
      the cost significantly.

PMID- 25593431
TI  - Timer switch to convert suction apparatus for negative pressure wound therapy
      application.

PMID- 25593432
TI  - Laser: The torch of freedom for ankyloglossia.
AB  - The tongue is an important oral structure that affects speech, position of teeth,
      periodontal tissues, nutrition, swallowing, nursing, and certain social
      activities. Ankyloglossia or tongue-tie, is a congenital anomaly characterized by
      an abnormally short lingual frenulum, which restricts mobility of the tongue.
      Though the ankyloglossia is not a serious condition, it may lead to a host of
      problems including infant feeding difficulties, speech disorders, and various
      mechanical and social issues related to the inability of the tongue to protrude.
      Hence, management of ankyloglossia should be considered at any age considering
      the risk-benefit evaluation. Tongue being highly vascular and mobile structure,
      laser-assisted lingual frenectomy is the simplest, safest and less traumatic of
      all the treatment modalities available, with most promising results in minimally
      invasive dentistry. Here, a case of ankyloglossia is reported with its management
      by diode laser. 

PMID- 25593433
TI  - Primary intra osseous venous malformation of nasal bone: A rare case report.
AB  - Primary intra osseous venous malformation with involvement of nasal bone is a
      rare phenomenon. Nasal bone intraosseous venous malformation on a back ground of
      port wine stain of face has not been reported in the available literature. We
      report the very rare case of intraosseous venous malformation of left nasal bone
      developing on a background of port wine stain of face, its diagnosis, pathology,
      management and review of literature. 

PMID- 25593434
TI  - Long term assessment of intralipotherapy in Madelung's disease.
AB  - Madelung's disease is characterised by multiple symmetric abnormal fat masses in
      the head, neck and upper limbs. Surgical excision or liposuction is the only
      realistic available option, although palliative in nature. The serial
      intralipotherapy with phosphatidylcholine/deoxycholate has been proposed as a non
      invasive treatment of Madelung's disease. The authors used serial
      intralipotherapy with phosphatidylcholine/deoxycholate in two patients affected
      by Madelung's disease. Three injections per lesion per patient were performed
      with 1 month's interval. Pre- and 6 months' post-treatment dimensions were
      assessed with ultrasound scan and patients were observed along a 5 years'
      clinical follow-up. A 42.5% average size reduction was reported in all treated
      lesions. About 33% recurrence rate was observed in the 5 years' follow-up. We
      confirm the efficacy of intralipotherapy in the non-invasive palliative treatment
      of Madelung's disease, as a valid option to reduce the volume and limit the
      growth of the pathological adipose masses. 

PMID- 25593435
TI  - Closure of chronic non healing ankle ulcer with low level laser therapy in a
      patient presenting with thalassemia intermedia: Case report.
AB  - In this single case study, the possible effect of low-level laser therapy (LLLT)
      was explored in the form of light emitting diodes on a chronic non-healing wound
      of 6 months duration in an 18-year-old male patient suffering from thalassemia
      intermedia. After irradiation, with LLLT dosage of 17.3 J/cm(2) for 8 min for 2
      weeks duration followed by proliferative dosage of 8.65-4.33 J/cm(2) for 4 min
      from 3(rd) week to 6(th) week for 2 min along with antibiotics vancomycin (15
      mg/kg) and a combination of amoxicillin and clavulanic acid (1 g). Proliferation
      of healthy granulation tissue was observed with decrease in score of pressure
      ulcer scale with complete re-epithelialization eventually LLLT irradiation could
      be a novel method of treatment for chronic non-healing wound in a thalassemia
      intermedia patient and an useful adjunct to standard care of treatment of
      pressure ulcers. It is postulated that LED irradiation augments wound healing
      with an early closure and no recurrence at the irradiated site even after follow
      up of 6 months. 

PMID- 25593436
TI  - Multiple bowel perforation and necrotising fasciitis secondary to abdominal
      liposuction in a patient with bilateral lumbar hernia.
AB  - We present a rare complication of abdominal liposuction: bowel perforation and
      necrotizing fasciitis. Because of bilateral lumbar hernia, a 56-year-old woman
      had caecum and descending colon perforation during lipoplasty. She had septic
      shock syndrome at her admission. The authors treated this complex wound with
      several debridement, omental flap, NPWT and split-thickness skin graft. The
      incidence of abdominal wall perforation with visceral injury is 14 in 100,000
      liposuctions performed. There are only 12 cases of bowel perforation in
      literature but this complication is probably underestimated. Prompt surgical
      debridement is absolutely mandatory in this life threatening scenario. Lumbar
      hernia is very rare and should be ruled out before every abdominal liposuction
      clinically or with imaging modalities. 

PMID- 25593437
TI  - Thermal burns on lower limb resulting from laptop use: A case report and review
      of literature.
AB  - We report a case of a 29-year-old man with a background history of incomplete
      quadriplegia, who sustained a second degree thermal burn of the lower limb from
      prolonged proximity to the extractor fan of his laptop. We have also reviewed all
      other reported cases of thermal burns associated with laptop use. This literature
      review highlights the variability in the extent of injury and the subsequent
      management of laptop induced burns. 

PMID- 25593438
TI  - Avulsion amputation of the ring finger managed by double cross finger flap: 25
      years follow-up.
AB  - Avulsion amputation of the fingers are rare. Current trend is to replant the
      avulsed tissue in spite of a high rate of failure. There are situations where
      replantation is not possible. Various salvage procedures have been mentioned. The
      author is presenting a 25 year follow up of a double cross finger flap done in
      1987. A similar procedure has been reported by other authors but with a short
      term follow up. 

PMID- 25593439
TI  - Salvage of a TRAM breast reconstruction flap using the retrograde internal
      mammary artery system.
AB  - BACKGROUND: Free tissue transfer provides an optimal means for breast
      reconstruction in creating an aesthetically natural appearance that is durable
      over time. The choice of donor vessels vary from surgeon to surgeon, but the
      internal mammary axis is one of the most popular choices together with the
      thoracodorsal vessels. AIMS AND RESULTS: We present the case of a salvaged free
      transverse rectus abdominis myocutaneous breast reconstruction in which end-to
      end antegrade anastomosis to the internal mammary artery (IMA) was not possible
      due to frail vessel walls, but retrograde anastomosis to the IMA and antegrade
      anastomosis of internal mammary vessel resulted in a perfused and viable flap.
      CONCLUSION: We suggest the use of the retrograde internal mammary arterial system
      for microsurgical anastomosis when the anterograde flow is not adequate, the
      vessel wall is friable, and when other more common options are not available.

PMID- 25593440
TI  - Giant rhinophyma: Excision with coblation assisted surgery.
AB  - An 83-year-old man presented with an unusually severe case of rhinophyma. Giant
      rhinopyhma is very rare in literature. The giant lesion was widely excised using
      sharp surgical incision and coblation assisted surgery. Using direct coblation to
      the nasal dorsum may cause edema in the surrounding tissue. There was minimal
      edema in surrounding tissue using this technique. A full thickness-skin graft was
      applied after excision. Cosmetic and functional postoperative results were
      satisfactory. 

PMID- 25593441
TI  - Variation of the latissimus dorsi.
AB  - A typical muscle variation of latissimus dorsi - the axillary arch is represented
      by the muscular or fibromuscular slip detached from the anteroinferior border of
      the musculus latissimus dorsi passing over the axilla under the axillary fascia
      crossing the medial side of the brachial plexus to continue as a septum
      intermusculare mediale brachii distally to the medial epicondyle of humerus. The
      full extent of the muscle is rarely present. Slips of muscle extend from the
      latissimus dorsi at the inferior angle of scapula to insert into pectoralis major
      (Langer), coracobrachilis, biceps or coracoid process forming what is described
      as a common variant - the muscular axillary arch. We report three cases of
      variants of latissimus dorsi, one of which has not been reported in the
      literature before. 

PMID- 25593442
TI  - A pregnant patient with fetal distress with severe post burn contracture of
      anterior trunk and perineum: A surgeon's nightmare!
AB  - INTRODUCTION: A case report of a pregnant lady in the third trimester, presenting
      in the emergency with absent fetal movements is being described. A multi
      speciality expertise was involved and a full term female baby was delivered.
      PRESENTATION: The patient presented in a Government hospital, Dehradun, India. At
      the time of presentation the fetal heart sounds were absent and subsequently the
      severe post-burn deformity involving the anterior trunk, perineum and thighs were
      discovered. MANAGEMENT: Immediately a multi-speciality approach involving the
      plastic, obstetrics and pediatrics field were called for and an emergency
      caesarean with simultaneous contracture release with split skin grafts were
      performed after optimizing the patient for surgery. CONCLUSION: This is one of
      the first case reports reporting this rare combination of post burn contracture
      of trunk and perineum with fetal distress requiring emergency caesarean section
      along with release of abdominal and perineal post-burn contracture. This case
      interestingly reinforces that in such complicated cases a systematic and a
      combined multi-speciality approach still holds the key to patient's treatment
      even in district hospitals.

PMID- 25593443
TI  - Post-operative brachial plexus neuropraxia: A less recognised complication of
      combined plastic and laparoscopic surgeries.
AB  - This presentation is to increase awareness of the potential for brachial plexus
      injury during prolonged combined plastic surgery procedures. A case of brachial
      plexus neuropraxia in a 26-year-old obese patient following a prolonged combined
      plastic surgery procedure was encountered. Nerve palsy due to faulty positioning
      on the operating table is commonly seen over the elbow and popliteal fossa.
      However, injury to the brachial plexus has been a recently reported phenomenon
      due to the increasing number of laparoscopic and robotic procedures. Brachial
      plexus injury needs to be recognised as a potential complication of prolonged
      combined plastic surgery. Preventive measures are discussed. 

PMID- 25593444
TI  - A novel technique for closure of post excisional soft tissue defects of axillary
      hidradenitis suppurativa.

PMID- 25593445
TI  - Invited Commentary: External tissue expansion and tension relief systems for
      improved utilisation of the viscoelastic properties of the skin in wound closure.

PMID- 25593446
TI  - Concrete scalp in trauma.

PMID- 25593447
TI  - The ulnar digital artery perforator flap: A new flap for little finger
      reconstruction- our experience and reply.

PMID- 25593449
TI  - Indelible voters' ink causing partial thickness burn over the fingers.

PMID- 25593448
TI  - Postoperative flare-up of tuberculosis following vaginoplasty.

PMID- 25593450
TI  - Superiorly based V flap for inguinal soft tissue defect reconstruction.

PMID- 25593451
TI  - "Bottle cap as bite block": An innovative intraoral splint.

PMID- 25593452
TI  - Taking the next step in documentation: Why and how?

PMID- 25593453
TI  - Telomere shortening as genetic risk factor of liver cirrhosis.
AB  - Cirrhosis is the main complication of chronic liver disease, leads to progressive
      liver function impairment and is the main risk factor for the development of
      liver cancer. Liver failure at endstage cirrhosis is associated with increased
      mortality with liver transplantation as the only possible treatment at this
      stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although
      the common factors leading to liver injury, such as viral hepatitis, alcohol
      consume or fatty liver disease can be identified in the majority of patients a
      small percentage of patients have no apparent risk factors. Moreover given the
      same risk factors, some patients progress to cirrhosis whereas others have a
      benign course, the reason remains unclear. In order to develop new diagnostic and
      therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis.
      The identification of genetic risk factors associated with cirrhosis is one of
      the possible approach to achieve these goal. In the past years several studies
      have supported the role of telomere shortening and cirrhosis. In the recent year
      several studies on the relation between several single nucleotide polymorphism
      (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis
      risk score based on seven SNPs. Also epidemiological studies on identical twins
      and in different ethnic groups have been supporting the importance of the role of
      genetic risk factors. Finally in the very recent years it has been suggested that
      telomere shortening may represent a genetic risk factor for the development of
      cirrhosis. 

PMID- 25593454
TI  - Role of the diet as a link between oxidative stress and liver diseases.
AB  - Oxidative stress is caused by an imbalance between the production of reactive
      oxygen (free radicals) and the body's ability (antioxidant capacity) to readily
      detoxify the reactive intermediates or easily repair the resulting damage. An
      adequate diet, characterized by daily intake of foods associated with
      improvements in the total antioxidant capacity of individuals and reduced
      incidence of diseases related to oxidation, can modulate the degree of oxidative
      stress. In fact, diet-derived micronutrients may be direct antioxidants, or are
      components of antioxidant enzymes, leading to improvement of some indicators of
      hepatic function. However, although their increased dietary intake might be
      beneficial, literature data are still controversial. This review summarizes what
      is known about the effects of diet nutrients on oxidative stress, inflammation
      and liver function. Moreover, we have analyzed: (1) the main nutritional
      components involved in the production and/or removal of free radicals; and (2)
      the role of free radicals in the pathogenesis of several hepatic diseases and
      related comorbidities. 

PMID- 25593457
TI  - Magnetic resonance imaging based rectal cancer classification: landmarks and
      technical standardization.
AB  - Rectal cancer classification is important to determine the preoperative
      chemoradiation therapy and to select appropriate surgical technique. We reviewed
      the Western and Japanese rectal cancer classification and we propose our new
      classification based of Magnetic resonance imaging (MRI). We determine the
      relation of the tumor to fixed parameters in MRI, which are peritoneal reflection
      and levator ani muscle. Then, we classify the rectal cancer into four levels
      based on tumor distal margin and invasion to MRI parameters. We applied all three
      classifications to 60 retrospectively collected patients of different rectal
      cancer distance and we compared our classifications to the others. Based on each
      level we standardize our surgical approach. For stages I-III, We found that level
      I where tumor distal margin is located above the peritoneal reflection and all of
      them were received low anterior resection (LAR) without chemoradiation. Level II
      where tumor distal margin is located from the peritoneal reflection and above the
      levator ani insertion on the rectum. 90% of them were received LAR +/-
      chemoradiation. Level III where tumor distal margin is located at the level of
      levator ani insertion or invading any part of the levator ani. 60% of them had
      ULAR + coloanal anastomosis +/- chemoradiation. Level IV where the tumor distal
      margin is located below the levator ani insertion; 77% were received APR +/-
      chemoradiation. The overall kappa for all levels between surgeons and radiologist
      was 0.93 (95%CI: 0.87-0.99), which is indicating almost perfect agreement. We
      concluded that the management of rectal tumors differed among each tumor level
      and our new MRI based classification might facilitate the prediction of surgical
      and chemoradiation management with better communication among a multidisciplinary
      team comparing to other classifications.

PMID- 25593455
TI  - Emerging concepts in liver graft preservation.
AB  - The urgent need to expand the donor pool in order to attend to the growing demand
      for liver transplantation has obliged physicians to consider the use of
      suboptimal liver grafts and also to redefine the preservation strategies. This
      review examines the different methods of liver graft preservation, focusing on
      the latest advances in both static cold storage and machine perfusion (MP). The
      new strategies for static cold storage are mainly designed to increase the fatty
      liver graft preservation via the supplementation of commercial organ preservation
      solutions with additives. In this paper we stress the importance of carrying out
      effective graft washout after static cold preservation, and present a detailed
      discussion of the future perspectives for dynamic graft preservation using MP at
      different temperatures (hypothermia at 4  degrees C, normothermia at 37  degrees
      C and subnormothermia at 20  degrees C-25  degrees C). Finally, we highlight some
      emerging applications of regenerative medicine in liver graft preservation. In
      conclusion, this review discusses the "state of the art" and future perspectives
      in static and dynamic liver graft preservation in order to improve graft
      viability.

PMID- 25593458
TI  - Gastric foregut cystic developmental malformation: case series and literature
      review.
AB  - Foregut cystic developmental malformation (FCDM) is a very rare lesion of the
      alimentary tract, especially in the stomach. We discuss the concepts of gastric
      duplication cyst, bronchogenic cysts, and FCDM. Nomenclature has been
      inconsistent and confusing, but, by some definitions, gastric duplication cysts
      involve gastric mucosa and submucosal glands, bronchogenic cysts involve
      respiratory mucosa with underlying cartilage and glands, and FCDM lacks gastric
      mucosa or underlying glands or cartilage but has pseudostratified ciliated
      columnar epithelium (PCCE). We searched our departmental case files from the past
      15 years and identified 12 cases of FCDM in the alimentary tract. We summarize
      the features of these 12 cases including a report in detail on a 52-year-old man
      with a submucosal cyst lined with simple PCCE and irregular and stratified
      circular muscle layers that merged with gastric smooth muscle bundles near the
      lesser curvature of the gastric cardia. A literature review of cases with this
      histology yielded 25 cases. We propose the term gastric-FCDM for such cases. Our
      own series of 12 cases confirms that preoperative recognition of the entity is
      infrequent and problematic. The rarity of this developmental disorder, as well as
      a lack of understanding of its embryologic origins, may contribute to missing the
      diagnosis. Not appreciating the diagnosis preoperatively can lead to an
      inappropriate surgical approach. In contrast, presurgical recognition of the
      entity will contribute to a good outcome and reduced risk of complications. 

PMID- 25593459
TI  - Increased density of tolerogenic dendritic cells in the small bowel mucosa of
      celiac patients.
AB  - AIM: To investigate the densities of dendritic cells (DCs) and FOXP3(+)
      regulatory T cells (Tregs) and their interrelations in the small bowel mucosa in
      untreated celiac disease (CD) patients with and without type 1 diabetes (T1D).
      METHODS: Seventy-four patients (45 female, 29 male, mean age 11.1 +/- 6.8 years)
      who underwent small bowel biopsy were studied. CD without T1D was diagnosed in 18
      patients, and CD with T1D was diagnosed in 15 patients. Normal small bowel mucosa
      was found in two T1D patients. Thirty-nine patients (mean age 12.8 +/- 4.9 years)
      with other diagnoses (functional dyspepsia, duodenal ulcer, erosive gastritis,
      etc.) formed the control group. All CD patients had partial or subtotal villous
      atrophy according to the Marsh classification: Marsh grade IIIa in 9, grade IIIb
      in 21 and grade IIIc in 3 cases. Thirty-nine patients without CD and 2 with T1D
      had normal small bowel mucosa (Marsh grade 0). The densities of CD11c(+), IDO(+),
      CD103(+), Langerin (CD207(+)) DCs and FOXP3(+) Tregs were investigated by
      immunohistochemistry (on paraffin-embedded specimens) and immunofluorescence (on
      cryostat sections) methods using a combination of mono- and double-staining.
      Sixty-six serum samples were tested for IgA-tissue transglutaminase (tTG) using a
      fully automated EliATM Celikey((r)) IgA assay (Pharmacia Diagnostics, Freiburg,
      Germany). RESULTS: The density of CD11c(+) DCs was significantly increased in CD
      patients compared with patients with normal mucosa (21.67 +/- 2.49 vs 13.58 +/-
      1.51, P = 0.007). The numbers of FOXP3(+) cells were significantly higher in CD
      patients (10.66 +/- 1.50 vs 1.92 +/- 0.37, P = 0.0002) and in patients with CD
      and coexisting T1D (8.11 +/- 1.64 vs 1.92 +/- 0.37, P = 0.002) compared with
      patients with normal mucosa. The density of FOXP3(+) cells significantly
      correlated with the histological grade of atrophic changes in the small bowel
      mucosa according to the March classification (r = 0.62; P < 0.0001) and with
      levels of IgA antibody (r = 0.55; P < 0.0001). The densities of IDO(+) DCs were
      significantly higher in CD patients (21.6 +/- 2.67 vs 6.26 +/- 0.84, P = 0.00003)
      and in patients with CD and coexisting T1D (19.08 +/- 3.61 vs 6.26 +/- 0.84, P =
      0.004) compared with patients with normal mucosa. A significant correlation was
      identified between the densities of IDO(+) DCs and FOXP3(+) T cells (r = 0.76; P
      = 0.0001). The mean values of CD103(+) DCs were significantly higher in CD
      patients (10.66 +/- 1.53 vs 6.34 +/- 0.61, P = 0.01) and in patients with CD and
      associated T1D (11.13 +/- 0.72 vs 6.34 +/- 0.61, P = 0.00002) compared with
      subjects with normal small bowel mucosa. The mean value of Langerin(+) DCs was
      higher in CD patients compared with persons with normal mucosa (7.4 +/- 0.92 vs
      5.64 +/- 0.46, P = 0.04). CONCLUSION: The participation of diverse DC subsets in
      the pathological processes of CD and the possible involvement of tolerogenic DCs
      in Tregs development to maintain intestinal immunological tolerance in CD
      patients are revealed.

PMID- 25593456
TI  - Management of hepatitis C in patients with chronic kidney disease.
AB  - Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney
      disease (CKD) subjects under hemodialysis and in kidney transplantation (KT)
      recipients, being an important cause of morbidity and mortality in these
      patients. The vast majority of HCV chronic infections in the hemodialysis setting
      are currently attributable to nosocomial transmission. Acute and chronic
      hepatitis C exhibits distinct clinical and laboratorial features, which can
      impact on management and treatment decisions. In hemodialysis subjects, acute
      infections are usually asymptomatic and anicteric; since spontaneous viral
      clearance is very uncommon in this context, acute infections should be treated as
      soon as possible. In KT recipients, the occurrence of acute hepatitis C can have
      a more severe course, with a rapid progression of liver fibrosis. In these
      patients, it is recommended to use pegylated interferon (PEG-IFN) in combination
      with ribavirin, with doses adjusted according to estimated glomerular filtration
      rate. There is no evidence suggesting that chronic hepatitis C exhibits a more
      aggressive course in CKD subjects under conservative management. In these
      subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD
      stage, rate of progression of renal dysfunction and the possibility of a
      preemptive transplant. HCV infection has been associated with both liver disease
      related deaths and cardiovascular mortality in hemodialysis patients. Among those
      individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia
      are often observed, and sequential HCV RNA monitoring is needed. Despite the poor
      tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many
      patients can achieve sustained virological response, which improve patient and
      graft outcomes. Hepatitis C eradication before KT theoretically improves survival
      and reduces the occurrence of chronic graft nephropathy, de novo
      glomerulonephritis and post-transplant diabetes mellitus. 

PMID- 25593460
TI  - Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor
      cells.
AB  - AIM: To determine whether the expression profiles of EphB receptor and ephrin-B
      ligand can be used as markers for dysplastic/oncogenic transformation in gastric
      mucosa. METHODS: The protein expression and localization of EphB and ephrin-B in
      normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a
      rat experimental model by immunolabeling, and mRNA expression was assessed in
      four human gastric carcinoma cell lines by reverse transcription-polymerase chain
      reaction. RESULTS: Ephrin-B- and EphB-expressing regions were divided along the
      pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the
      experimental ulcer, and its expression domain extended to gastric pits and/or the
      luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and
      ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than
      one ligand-receptor pair was highly expressed in each of the gastric carcinoma
      cell lines. CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a
      feature common to experimentally induced gastric dysplasia and human gastric
      carcinoma cell lines as compared to normal gastric and ulcerated regenerating
      epithelia. Thus, EphB/ephrin-B may be a useful marker combination for
      dysplastic/oncogenic transformation in gastric cancer.

PMID- 25593462
TI  - Chemokine ligand 20 enhances progression of hepatocellular carcinoma via
      epithelial-mesenchymal transition.
AB  - AIM: To identify the mechanisms of chemokine ligand 20 (CCL20)-induced
      hepatocellular carcinoma (HCC) metastasis and evaluate it as a prognostic marker.
      METHODS: Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues
      from 62 patients who underwent curative resection. The relationship between CCL20
      expression and clinicopathologic features was analyzed. Univariate and
      multivariate analyses were performed to evaluate its predictive value for
      recurrence and survival of HCC patients. The expression levels of epithelial
      mesenchymal transition (EMT)-and signaling pathway-related proteins were
      evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on
      HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenoltetrazolium bromide (MTT) and Transwell assays. RESULTS: CCL20
      immunoreactivity was detected in all 62 patient specimens. CCL20 expression was
      associated with preoperative alpha-fetoprotein level (P = 0.043), tumor size (P =
      0.000), tumor number (P = 0.008), vascular invasion (P = 0.014), and tumor
      differentiation (P = 0.007). Patients with high CCL20 expression had poorer
      recurrence-free and overall survivals compared to those with low CCL20 expression
      (both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their
      proliferation and migration ability (P < 0.05). Western blotting and
      immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in
      HCC cells, and increased expression of phosphorylated AKT, beta-catenin and
      vimentin, and decreased E-cadherin expression (P < 0.05). The correlation
      analysis revealed that high CCL20 expression in HCC tissue specimens was
      negatively correlated with E-cadherin expression (13.33%, 4/30), and positively
      correlated with vimentin (90.0%, 27/30), beta-catenin (96.67%, 29/30) and p-AKT
      (76.67%, 23/30) expression. CONCLUSION: CCL20 expression is associated with HCC
      recurrence and patient survival and promotes HCC cell proliferation and migration
      by inducing EMT-like changes via PI3K/AKT and Wnt/beta-catenin pathways.

PMID- 25593461
TI  - Butein effects in colitis and interleukin-6/signal transducer and activator of
      transcription 3 expression.
AB  - AIM: To evaluate the effects of butein on inflammatory cytokines, matrix
      metalloproteinase-9 (MMP-9), and colitis in interleukin (IL)-10(-/-) mice.
      METHODS: To synchronize colitis, 8- to 10-wk-old IL-10(-/-) mice were fed pellet
      chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or
      butein (1 mg/kg per day, ip) was injected for 4 wk. Histologic scores,
      inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator
      of transcription 3 (pSTAT3) expressions were analyzed in IL-10(-/-) mice and in
      Colo 205 cells. RESULTS: Butein reduced the colonic inflammatory score by > 50%.
      Expression levels of IL-6, IL-1beta, interferon (IFN)-gamma and MMP-9 were
      decreased in the colons of mice exposed to butein, whereas other inflammatory
      cytokines (IL-17A, IL-21 and IL-22) were unchanged. Immunohistochemical staining
      for pSTAT3 and MMP-9 was significantly decreased in the butein-treated groups
      compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in
      Colo 205 cells. CONCLUSION: Butein ameliorated colitis in IL-10(-/-) mice by
      regulating IL-6/STAT3 and MMP-9 activation.

PMID- 25593463
TI  - Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in
      obstructive jaundice rats.
AB  - AIM: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the
      intestinal barrier of rats with obstructive jaundice and determine the possible
      mechanisms of action involved in the protective effect. METHODS: Thirty-six
      Sprague-Dawley rats were randomly divided into a sham operation group, an
      obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats.
      The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the
      other two groups were treated with the same concentration of normal saline.
      Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were
      recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14(th) day, body weight,
      the wet weight of the small intestine, pathological changes of the small
      intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the
      small intestinal lamina propria were recorded for each group. RESULTS: In the rat
      model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile
      duct ligation. Compared with the sham operation group, the obstructive jaundice
      group displayed increased yellow staining of abdominal visceral serosa, decreased
      small intestine wet weight, thinning of the intestinal muscle layer and villi,
      villous atrophy, uneven height, fusion, partial villous epithelial cell shedding,
      substantial inflammatory cell infiltration and significantly reduced IgA
      expression. However, no significant gross changes were noted between the GLP-2
      and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP
      2 group were significantly increased compared with the sham group (P < 0.01). The
      increasing levels of the aforementioned markers were more significant in the
      obstructive jaundice group than in the GLP-2 group (P < 0.01). CONCLUSION: GLP-2
      reduces intestinal mucosal injuries in obstructive jaundice rats, which might be
      attributed to increased intestinal IgA and reduced bilirubin and endotoxin.

PMID- 25593465
TI  - Hepatitis B virus infection, diabetes mellitus, and their synergism for
      cholangiocarcinoma development: a case-control study in Korea.
AB  - AIM: To identify possible risk factors and their synergism for cholangiocarcinoma
      development. METHODS: A hospital-based, case-control study in which we included
      276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma (ECC) and 83
      intrahepatic cholangiocarcinoma (ICC)], diagnosed at a training hospital in Korea
      between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and
      date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism
      between those factors were evaluated using conditional logistic regression and
      synergism index, respectively. RESULTS: There was an association between
      cholangiocarcinoma and hepatitis B virus (HBV) infection, diabetes mellitus (DM),
      cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted
      odds ratios (AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic
      interaction on the additive model was investigated between HBV infection and DM
      (AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis,
      choledocholithiasis, hepatolithiasis, and DM were significant risk factors for
      ECC (AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis,
      hepatolithiasis, HBV infection, and DM were risk factors for ICC (AOR = 8.6,
      157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed
      between HBV infection and DM (OR = 22.7; 95%CI: 2.4-214.1). However, there was no
      synergistic interaction between other significant risk factors for
      cholangiocarcinoma. CONCLUSION: In this Korean study, HBV infection and DM were
      found to exert independent and synergistic effects on the risk for
      cholangiocarcinoma, including ICC. Exploring the underlying mechanisms for such
      synergy may lead to the development of cholangiocarcinoma prevention strategies
      in high-risk individuals.

PMID- 25593464
TI  - E2F-1 overexpression inhibits human gastric cancer MGC-803 cell growth in vivo.
AB  - AIM: To evaluate the influence of E2F-1 on the growth of human gastric cancer
      (GC) cells in vivo and the mechanism involved. METHODS: E2F-1 recombinant
      lentiviral vectors were injected into xenograft tumors of MGC-803 cells in nude
      mice, and then tumor growth was investigated. Overexpression of transcription
      factor E2F-1 was assessed by reverse transcription-polymerase chain reaction (RT
      PCR) and Western blotting analysis. Apoptosis rates were determined using a
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) assay. Expression levels of certain cell cycle regulators and apoptosis
      related proteins, such as Bax, survivin, Bcl-2, cyclin D1, S-phase kinase
      associated protein 2, and c-Myc were examined by Western blotting and RT-PCR.
      RESULTS: Xenograft tumors of MGC-803 cells in nude mice injected with E2F-1
      recombinant lentiviral vectors stably overexpressed the E2F-1 gene as measured by
      semi-quantitative RT-PCR (relative mRNA expression: 0.10 +/- 0.02 vs 0.05 +/-
      0.02 for control vector and 0.06 +/- 0.03 for no infection; both P < 0.01) and
      Western blotting (relative protein expression: 1.90 +/- 0.05 vs 1.10 +/- 0.03 in
      control vector infected and 1.11 +/- 0.02 for no infection; both P < 0.01). The
      growth-curve of tumor volumes revealed that infection with E2F-1 recombinant
      lentiviral vectors significantly inhibited the growth of human GC xenografts
      (2.81 +/- 1.02 vs 6.18 +/- 1.15 in control vector infected and 5.87 +/- 1.23 with
      no infection; both P < 0.05) at 15 d after treatment. TUNEL analysis demonstrated
      that E2F-1 overexpression promoted tumor cell apoptosis (18.6% +/- 2.3% vs 6.7%
      +/- 1.2% in control vector infected 6.3% +/- 1.2% for no infection; both P <
      0.05). Furthermore, lentiviral vector-mediated E2F-1 overexpression increased the
      expression of Bax and suppressed survivin, Bcl-2, cyclin D1, Skp2, and c-Myc
      expression in tumor tissue. CONCLUSION: E2F-1 inhibits growth of GC cells via
      regulating multiple signaling pathways, and may play an important role in
      targeted therapy for GC.

PMID- 25593466
TI  - miRNA-103: molecular link between insulin resistance and nonalcoholic fatty liver
      disease.
AB  - AIM: To investigate the associations between miRNA-103 (miR-103) and insulin
      resistance and nonalcoholic fatty liver disease (NAFLD). METHODS: Serum samples
      were collected from 50 NAFLD patients who were overweight or obese (NAFLD group)
      and from 30 healthy subjects who served as controls (normal control group).
      Quantitative polymerase chain reaction was used to detect expression of miR-103.
      Fasting plasma glucose, fasting insulin, and triglyceride (TG) levels were
      measured. Homeostasis model assessment was used to evaluate basal insulin
      resistance (HOMA-IR). Patient height and weight were measured to calculate body
      mass index (BMI). RESULTS: Compared with the normal control group, higher serum
      levels of miR-103 were expressed in the NAFLD group (8.18 +/- 0.73 vs 4.23 +/-
      0.81, P = 0.000). When P = 0.01 (bilateral), miR-103 was positively correlated
      with HOMA-IR (r = 0.881), TG (r = 0.774) and BMI (r = 0.878), respectively. miR
      103, TG and BMI were all independent factors for HOMA-IR (beta =
      0.438/0.657/0.251, P = 0.000/0.007/0.001). miR-103, TG, BMI and HOMA-IR were all
      risk factors for NAFLD (odds ratio = 2.411/16.196/1.574/19.11, P =
      0.009/0.022/0.01/0.014). CONCLUSION: miR-103 is involved in insulin resistance
      and NAFLD, and may be a molecular link between insulin resistance and NAFLD and a
      therapeutic target for these disorders.

PMID- 25593467
TI  - Assessment of liver ablation using cone beam computed tomography.
AB  - AIM: To investigate the feasibility and accuracy of cone beam computed tomography
      (CBCT) in assessing the ablation zone after liver tumor ablation. METHODS: Twenty
      three patients (17 men and 6 women, range: 45-85 years old, mean age 65 years)
      with malignant liver tumors underwent ultrasound-guided percutaneous tumor
      ablation [radiofrequency (n = 14), microwave (n = 9)] followed by intravenous
      contrast-enhanced CBCT. Baseline multidetector computed tomography (MDCT) and
      peri-procedural CBCT images were compared. CBCT image quality was assessed as
      poor, good, or excellent. Image fusion was performed to assess tumor coverage,
      and quality of fusion was rated as bad, good, or excellent. Ablation zone volumes
      on peri-procedural CBCT and post-procedural MDCT were compared using the non
      parametric paired Wilcoxon t-test. RESULTS: Rate of primary ablation
      effectiveness was 100%. There were no complications related to ablation. Local
      tumor recurrence and new liver tumors were found 3 mo after initial treatment in
      one patient (4%). The ablation zone was identified in 21/23 (91.3%) patients on
      CBCT. The fusion of baseline MDCT and peri-procedural CBCT images was feasible in
      all patients and showed satisfactory tumor coverage (at least 5-mm margin). CBCT
      image quality was poor, good, and excellent in 2 (9%), 8 (35%), and 13 (56%),
      patients respectively. Registration quality between peri-procedural CBCT and post
      procedural MDCT images was good to excellent in 17/23 (74%) patients. The median
      ablation volume on peri-procedural CBCT and post-procedural MDCT was 30 cm(3)
      (range: 4-95 cm(3)) and 30 cm(3) (range: 4-124 cm(3)), respectively (P-value >
      0.2). There was a good correlation (r = 0.79) between the volumes of the two
      techniques. CONCLUSION: Contrast-enhanced CBCT after tumor ablation of the liver
      allows early assessment of the ablation zone.

PMID- 25593468
TI  - Patient age and duration of colonoscopy are predictors for adenoma detection in
      both proximal and distal colon.
AB  - AIM: To investigate the relation of patient characteristics and procedural
      parameters to the endoscopic detection rate of colonic adenomas. Further to
      study, which factors may be capable to predict the localization of adenomatous
      lesions. METHODS: We used the data base of a prospective randomized colonoscopy
      study (The ColoCap trial) to identify patients being diagnosed with colon
      adenoma. Logistic regression analysis was conducted to reveal predictors for
      adenoma detection in the entire colon and also with respect to the proximal and
      distal part. Covariates including age, gender, duration of colonoscopy and
      comorbidities were defined to determine association between predictors and
      adenoma detection. RESULTS: Equal numbers of adenomas were detected in the
      proximal and distal side of the splenic flexure [126 (57%) vs 94 (43%), P =
      0.104]. Simultaneous occurrence of adenomas in both sides of the colon was rare.
      The appearance of both proximal and distal adenoma was associated with increasing
      age (P = 0.008 and P = 0.024) and increasing duration of colonoscopy (P < 0.001
      and P = 0.001). Male gender was a predictor for adenoma detection in the proximal
      colon (P = 0.008) but statistical significance was slightly missed with respect
      to the distal colon (P = 0.089). Alcohol abuse was found to be a predictor for
      the detection of distal adenoma (P = 0.041). CONCLUSION: Increasing age and
      longer duration of colonoscopy are factors with a strong impact on adenoma
      detection both in the proximal and distal colon. Since proximal adenomas occurred
      in absence of distal adenomas, complete colonoscopy should be performed for
      screening.

PMID- 25593469
TI  - Thrombomodulin in the management of acute cholangitis-induced disseminated
      intravascular coagulation.
AB  - AIM: To evaluate the need for thrombomodulin (rTM) therapy for disseminated
      intravascular coagulation (DIC) in patients with acute cholangitis (AC)-induced
      DIC. METHODS: Sixty-six patients who were diagnosed with AC-induced DIC and who
      were treated at our hospital were enrolled in this study. The diagnoses of AC and
      DIC were made based on the 2013 Tokyo Guidelines and the DIC diagnostic criteria
      as defined by the Japanese Association for Acute Medicine, respectively. Thirty
      consecutive patients who were treated with rTM between April 2010 and September
      2013 (rTM group) were compared to 36 patients who were treated without rTM
      (before the introduction of rTM therapy at our hospital) between January 2005 and
      January 2010 (control group). The two groups were compared in terms of patient
      characteristics at the time of DIC diagnosis (including age, sex, primary
      disease, severity of cholangitis, DIC score, biliary drainage, and anti-DIC
      drugs), the DIC resolution rate, DIC score, the systemic inflammatory response
      syndrome (SIRS) score, hematological values, and outcomes. Using logistic
      regression analysis based on multivariate analyses, we also examined factors that
      contributed to persistent DIC. RESULTS: There were no differences between the rTM
      group and the control group in terms of the patients' backgrounds other than
      administration. DIC resolution rates on day 9 were higher in the rTM group than
      in the control group (83.3% vs 52.8%, P < 0.01). The mean DIC scores on day 7
      were lower in the rTM group than in the control group (2.1 +/- 2.1 vs 3.5 +/-
      2.3, P = 0.02). The mean SIRS scores on day 3 were significantly lower in the rTM
      group than in the control group (1.1 +/- 1.1 vs 1.8 +/- 1.1, P = 0.03). Mortality
      on day 28 was 13.3% in the rTM group and 27.8% in the control group; these rates
      were not significantly different (P = 0.26). Multivariate analysis identified
      only the absence of biliary drainage as significantly associated with persistent
      DIC (P < 0.01, OR = 12, 95%CI: 2.3-60). Although the difference did not reach
      statistical significance, primary diseases (malignancies) (P = 0.055, OR = 3.9,
      95%CI: 0.97-16) and the non-use of rTM had a tendency to be associated with
      persistent DIC (P = 0.08, OR = 4.3, 95%CI: 0.84-22). CONCLUSION: The add-on
      effects of rTM are anticipated in the treatment of AC-induced DIC, although
      biliary drainage for AC remains crucial.

PMID- 25593470
TI  - Mutations of pre-core and basal core promoter before and after hepatitis B e
      antigen seroconversion.
AB  - AIM: To investigate the role of pre-core and basal core promoter (BCP) mutations
      before and after hepatitis B e antigen (HBeAg) seroconversion. METHODS: The
      proportion of pre-core (G1896A) and basal core promoter (A1762T and G1764A)
      mutant viruses and serum levels of hepatitis B virus (HBV) DNA, hepatitis B
      surface antigen (HBsAg), and HB core-related antigen were analyzed in chronic
      hepatitis B patients before and after HBeAg seroconversion (n = 25), in those who
      were persistently HBeAg positive (n = 18), and in those who were persistently
      anti-HBe positive (n = 43). All patients were infected with HBV genotype C and
      were followed for a median of 9 years. RESULTS: Although the pre-core mutant
      became predominant (24% to 65%, P = 0.022) in the HBeAg seroconversion group
      during follow-up, the proportion of the basal core promoter mutation did not
      change. Median HBV viral markers were significantly higher in patients without
      the mutations in an HBeAg positive status (HBV DNA: P = 0.003; HBsAg: P < 0.001;
      HB core-related antigen: P = 0.001). In contrast, HBV DNA (P = 0.012) and HBsAg
      (P = 0.041) levels were significantly higher in patients with the pre-core
      mutation in an anti-HBe positive status. CONCLUSION: There is an opposite
      association of the pre-core mutation with viral load before and after HBeAg
      seroconversion in patients with HBV infection.

PMID- 25593472
TI  - Histological mixed-type as an independent prognostic factor in stage I gastric
      carcinoma.
AB  - AIM: To evaluate the clinicopathological features of mixed-type gastric cancer
      and their influence on prognosis of mixed-type stage I gastric cancer. METHODS:
      We analyzed 446 patients who underwent curative gastrectomy for stage I gastric
      cancer between 1999 and 2009. The patients were divided into two groups: those
      with differentiated or undifferentiated cancer (non-mixed-type, n = 333) and
      those with a mixture of differentiated and undifferentiated cancers (mixed-type,
      n = 113). RESULTS: The overall prevalence of mixed-type gastric cancer was 25.3%
      (113/446). Compared with patients with non-mixed-type gastric cancer, those with
      mixed-type gastric cancer tended to be older at onset (P = 0.1252) and have a
      higher incidence of lymph node metastasis (P = 0.1476). They also had
      significantly larger tumors (P < 0.0001), more aggressive lymphatic invasion (P =
      0.0011), and deeper tumor invasion (P < 0.0001). In addition, they exhibited
      significantly worse overall survival rates than did patients with non-mixed-type
      gastric cancer (P = 0.0026). Furthermore, mixed-type gastric cancer was
      independently associated with a worse outcome in multivariate analysis [P =
      0.0300, hazard ratio = 11.4 (1.265-102.7)]. CONCLUSION: Histological mixed-type
      of gastric cancer contributes to malignant outcomes and highlight its usefulness
      as a prognostic indicator in stage I gastric cancer.

PMID- 25593474
TI  - Computed tomography and magnetic resonance imaging evaluation of lymph node
      metastasis in early colorectal cancer.
AB  - AIM: To assess the role of computed tomography (CT) and magnetic resonance
      imaging (MRI) and establish imaging criteria of lymph node metastasis in early
      colorectal cancer. METHODS: One hundred and sixty patients with early colorectal
      cancer were evaluated for tumor location, clinical history of polypectomy, depth
      of tumor invasion, and lymph node metastasis. Two radiologists assessed
      preoperative CT and/or MRI for the primary tumor site detectability, the presence
      or absence of regional lymph node, and the size of the largest lymph node.
      Demographic, imaging, and pathologic findings were compared between the two
      groups of patients based on pathologic lymph node metastasis and optimal size
      criterion was obtained. RESULTS: The locations of tumor were ascending,
      transverse, descending, sigmoid colon, and rectum. One hundred and sixty early
      colorectal cancers were classified into 3 groups based on the pathological depth
      of tumor invasion; mucosa, submucosa, and depth unavailable. A total of 20
      (12.5%) cancers with submucosal invasion showed lymph node metastasis. Lymph
      nodes were detected on CT or MRI in 53 patients. The detection rate and size of
      lymph nodes were significantly higher (P = 0.000, P = 0.044, respectively) in
      patients with pathologic nodal metastasis than in patients without nodal
      metastasis. Receiver operating curve analysis showed that a cut-off value of 4.1
      mm is optimal with a sensitivity of 78.6% and specificity of 75%. CONCLUSION: The
      short diameter size criterion of >= 4.1 mm for metastatic lymph nodes was optimal
      for nodal staging in early colorectal cancer.

PMID- 25593475
TI  - Impression of prognosis regarding pathologic stage after preoperative
      chemoradiotherapy in rectal cancer.
AB  - AIM: To ascertain pathologic stage as a prognostic indicator for rectal cancer
      patients receiving preoperative chemoradiotherapy (PCRT). METHODS: Patients with
      mid- and low rectal carcinoma (magnetic resonance imaging - based clinical stage
      II or III) between 2000 and 2009 and treated with curative radical resection were
      identified. Patients were divided into two groups: PCRT and No-PCRT. Recurrence
      free survival (RFS) was examined according to pathologic stage and addition of
      adjuvant treatment. RESULTS: Overall, 894 patients were identified. Of these, 500
      patients received PCRT. Adjuvant chemotherapy was delivered to 81.5% of the No
      PCRT and 94.8% of the PCRT patients. Adjuvant radiotherapy was given to 29.4% of
      the patients in the No PCRT group. The 5-year RFS for the No-PCRT group was 92.6%
      for Stage I, 83.3% for Stage II, and 72.9% for Stage III. The 5-year RFS for the
      PCRT group was 95.2% for yp Stage 0, 91.7% for yp Stage I, 73.9% for yp Stage II,
      and 50.7% for yp Stage III. CONCLUSION: Pathologic stage can predict prognosis in
      PCRT patients. 5-year RFS is significantly lower among PCRT patients than No-PCRT
      patients in pathologic stage II and III. These results should be taken into
      account when considering adjuvant treatment for patients treated with PCRT.

PMID- 25593479
TI  - Submucosal tunneling and endoscopic resection of submucosal tumors at the
      esophagogastric junction.
AB  - AIM: To evaluate the safety and efficacy of submucosal tunneling and endoscopic
      resection (STER) for treating submucosal tumors (SMTs). METHODS: Between August
      2012 and October 2013, 21 patients with SMTs originating from the muscularis
      propria (MP) layer at the esophagogastric junction were treated by STER of their
      tumors. Key steps of the procedure include: (1) mucosal incision: a 2-cm
      longitudinal mucosal incision was made 5 cm proximal to the tumor; (2) submucosal
      tunneling: a submucosal tunnel was created 5 cm proximal to and 1 to 2 cm distal
      to the tumor; (3) tumor resection: the SMT was resected under direct endoscopic
      viewing; (4) hemostasis: while finishing the tumor resection, careful hemostasis
      of the MP defect and the tunnel was performed; and (5) mucosal closure: the
      mucosal incision site was closed by using hemostatic clips. During the operation,
      equipment used included a cap-fitted endoscope, an insulated-tip knife, a hook
      knife, hemostatic forceps, an injection needle, a snare, an endoclip, and a high
      frequency generator. Carbon dioxide (CO2) insufflation was achieved by using a
      CO2 insufflator. RESULTS: The median age of the patients was 46.2 years (range,
      35-59 years), and the majority were male (18 male vs 3 female). Complete
      resection rate was 100% (21/21). Eighteen lesions were resected en bloc. Mean
      tumor size was 23 mm (range, 10-40 mm), and mean procedure time was 62.9 min
      (range, 45-90 min). Pathological diagnosis of these tumors included leiomyoma (15
      out of 21) and gastrointestinal stromal tumor (6 out of 21). Full-thickness MP
      resection was performed in 9 of 21 patients (42.9%), with mediastinal and
      subcutaneous emphysema occurring in all nine. At the completion of the procedure,
      all patients received closure of the incision with hemoclips. One patient
      required percutaneous drainage. The remaining 20 patients required no further
      endoscopic or surgical intervention. There were no incidents of massive or
      delayed bleeding. The median follow-up period after the procedure was 6 mo
      (range, 2-14 mo). During follow-up, no patients were found to have residual or
      recurrent tumor or esophageal stricture. CONCLUSION: STER is safe, effective and
      feasible, which provides accurate histopathologic evaluation and curative
      treatment for SMTs originating from the MP layer at the esophagogastric junction.

PMID- 25593477
TI  - Clinicopathologic factors and molecular markers related to lymph node metastasis
      in early gastric cancer.
AB  - AIM: To analyze predictive factors for lymph node metastasis in early gastric
      cancer. METHODS: We analyzed 1104 patients with early gastric cancer (EGC) who
      underwent a gastrectomy with lymph-node dissection from May 2003 through July
      2011. The clinicopathologic factors and molecular markers were assessed as
      predictors for lymph node metastasis. Molecular markers such as microsatellite
      instability, human mutL homolog 1, p53, epidermal growth factor receptor (EGFR)
      and human epidermal growth factor receptor 2 (HER2) were included. The chi(2)
      test and logistic regression analysis were used to determine clinicopathologic
      parameters. RESULTS: Lymph node metastasis was observed in 104 (9.4%) of 1104
      patients. Among 104 cases of lymph node positive patients, 24 patients (3.8%)
      were mucosal cancers and 80 patients (16.7%) were submucosal. According to
      histologic evaluation, the number of lymph node metastasis found was 4 (1.7%) for
      well differentiated tubular adenocarcinoma, 45 (11.3%) for moderately
      differentiated tubular adenocarcinoma, 36 (14.8%) for poorly differentiated
      tubular adenocarcinoma, and 19 (8.4%) for signet ring cell carcinoma. Of 690 EGC
      cases, 77 cases (11.2%) showed EGFR overexpression. HER2 overexpression was
      present in 110 cases (27.1%) of 406 EGC patients. With multivariate analysis,
      female gender (OR = 2.281, P = 0.009), presence of lymphovascular invasion (OR =
      10.950, P < 0.0001), diameter (>= 20 mm, OR = 3.173, P = 0.01), and EGFR
      overexpression (OR = 2.185, P = 0.044) were independent risk factors for lymph
      node involvement. CONCLUSION: Female gender, tumor size, lymphovascular invasion
      and EGFR overexpression were predictive risk factors for lymph node metastasis in
      EGC.

PMID- 25593480
TI  - Prophylaxis against hepatitis B virus recurrence after liver transplantation: a
      registry study.
AB  - AIM: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin (HBIG)
      in combination with different nucleos(t)ide analogues. METHODS: A total of 5333
      hepatitis B surface antigen-positive patients from the China Liver Transplant
      Registry database were enrolled between January 2000 and December 2009. Low-dose
      intramuscular (im) HBIG combined with one nucleos(t)ide analogue has been shown
      to be very cost-effective in recent reports. Hepatitis B virus (HBV) prophylactic
      outcomes were compared based on their posttransplant prophylactic protocols
      [group A (n = 4684): im HBIG plus lamivudine; group B (n = 491): im HBIG plus
      entecavir; group C (n = 158): im HBIG plus adefovir dipivoxil]. We compared the
      related baseline characteristics among the three groups, including the age, male
      sex, Meld score at the time of transplantation, Child-Pugh score at the time of
      transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre
      transplantation HBV deoxyribonucleic acid (HBV DNA) positivity, HBV DNA at the
      time of transplantation, pre-transplantation antiviral therapy, and the duration
      of antiviral therapy before transplantation of the patients. We also calculated
      the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the
      different groups. All potential risk factors were analyzed using univariate and
      multivariate analyses. RESULTS: The mean follow-up duration was 42.1 +/- 30.3 mo.
      The 1-, 3- and 5-year survival rates were lower in group A than in groups B
      (86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P < 0.001) and C
      (86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P < 0.001). The 1
      , 3- and 5-year posttransplant HBV recurrence rates were significantly higher in
      group A than in group B (1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively,
      P = 0.023). No significant difference existed between groups A and C and between
      groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates.
      Pretransplant hepatocellular carcinoma, high viral load and posttransplant
      prophylactic protocol (lamivudine and HBIG vs entecavir and HBIG) were associated
      with HBV recurrence. CONCLUSION: Low-dose intramuscular HBIG in combination with
      a nucleos(t)ide analogue provides effective prophylaxis against posttransplant
      HBV recurrence, especially for HBIG plus entecavir.

PMID- 25593483
TI  - Short turn radius colonoscope in an anatomical model: retroflexed withdrawal and
      detection of hidden polyps.
AB  - AIM: To evaluate the new RetroViewTM colonoscope and compare its ability to
      detect simulated polyps "hidden" behind colonic folds with that of a conventional
      colonoscope, utilizing anatomic colon models. METHODS: Three anatomic colon
      models were prepared, with twelve simulated polyps "hidden" behind haustral folds
      and five placed in easily viewed locations in each model. Five blinded
      endoscopists examined two colon models in random order with the conventional or
      RetroViewTM colonoscope, utilizing standard withdrawal technique. The third colon
      model was then examined with the RetroViewTM colonoscope withdrawn initially in
      retroflexion and then in standard withdrawal. Polyp detection rates during
      standard and retroflexed withdrawal of the conventional and RetroViewTM
      colonoscopes were determined. Polyp detection rates for combined standard and
      retroflexed withdrawal (combination withdrawal) with the RetroViewTM colonoscope
      were also determined. RESULTS: For hidden polyps, retroflexed withdrawal using
      the RetroViewTM colonoscope detected more polyps than the conventional
      colonoscope in standard withdrawal (85% vs 12%, P = 0.0001). For hidden polyps,
      combination withdrawal with the RetroViewTM colonoscope detected more polyps than
      the conventional colonoscope in standard withdrawal (93% vs 12%, P <= 0.0001).
      The RetroViewTM colonoscope in "combination withdrawal" was superior to other
      methods in detecting all (hidden + easily visible) polyps, with successful
      detection of 80 of 85 polyps (94%) compared to 28 (32%) polyps detected by the
      conventional colonoscope in standard withdrawal (P < 0.0001) and 67 (79%) polyps
      detected by the RetroViewTM colonoscope in retroflexed withdrawal alone (P <
      0.01). Continuous withdrawal of the colonoscope through the colon model while
      retroflexed was achieved by all endoscopists. In a post-test survey, four out of
      five colonoscopists reported that manipulation of the colonoscope was easy or
      very easy. CONCLUSION: In simulated testing, the RetroViewTM colonoscope
      increased detection of hidden polyps. Combining standard withdrawal with
      retroflexed withdrawal may become the new paradigm for "complete screening
      colonoscopy".

PMID- 25593485
TI  - Intervention to increase physical activity in irritable bowel syndrome shows long
      term positive effects.
AB  - AIM: To assess the long-term effects of physical activity on irritable bowel
      syndrome (IBS) symptoms and on quality of life, fatigue, depression and anxiety.
      METHODS: Seventy-six patients from a previous randomized controlled
      interventional study on increased physical activity in IBS were asked to
      participate in this long-term follow-up study. The included patients attended one
      visit in which they filled out questionnaires and they underwent a submaximal
      cycle ergometer test. The primary end point was the change in the IBS Severity
      Scoring System (IBS-SSS) at baseline, i.e., before the intervention and at follow
      up. The secondary endpoints were changes in quality of life, fatigue, depression
      and anxiety. RESULTS: A total of 39 [32 women, median age 45 (28-61) years]
      patients were included in this follow-up. Median follow-up time was 5.2 (range:
      3.8-6.2) years. The IBS symptoms were improved compared with baseline [IBS-SSS:
      276 (169-360) vs 218 (82-328), P = 0.001]. This was also true for the majority of
      the dimensions of psychological symptoms such as disease specific quality of
      life, fatigue, depression and anxiety. The reported time of physical activity
      during the week before the visit had increased from 3.2 (0.0-10.0) h at baseline
      to 5.2 (0.0-15.0) h at follow-up, P = 0.019. The most common activities reported
      were walking, aerobics and cycling. There was no significant difference in the
      oxygen uptake 31.8 (19.7-45.8) mL per min per kg at baseline vs 34.6 (19.0-54.6)
      mL/min per kg at follow-up. CONCLUSION: An intervention to increase physical
      activity has positive long-term effects on IBS symptoms and psychological
      symptoms.

PMID- 25593494
TI  - Profiling cellular bioenergetics, glutathione levels, and caspase activities in
      stomach biopsies of patients with upper gastrointestinal symptoms.
AB  - AIM: To measure biochemical parameters in stomach biopsies and test their
      suitability as diagnostic biomarkers for gastritis and precancerous lesions.
      METHODS: Biopsies were obtained from the stomachs of two groups of patients (n =
      40) undergoing fiber-optic endoscopy due to upper gastrointestinal symptoms. In
      the first group (n = 17), only the corpus region was examined. Biopsies were
      processed for microscopic examination and measurement of mitochondrial O2
      consumption (cellular respiration), cellular adenosine triphosphate (ATP),
      glutathione (GSH), and caspase activity. In the second group of patients (n =
      23), both corpus and antral regions were studied. Some biopsies were processed
      for microscopic examination, while the others were used for measurements of
      cellular respiration and GSH level. RESULTS: Microscopic examinations of gastric
      corpus biopsies from 17 patients revealed normal mucosae in 8 patients,
      superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient.
      In patients with normal histology, the rate (mean +/- SD) of cellular respiration
      was 0.17 +/- 0.02 MUmol/L O2 min(-1) mg(-1), ATP content was 487 +/- 493 pmol/mg,
      and GSH was 469 +/- 98 pmol/mg. Caspase activity was detected in 3 out of 8
      specimens. The values of ATP and caspase activity were highly variable. The
      presence of superficial gastritis had insignificant effects on the measured
      biomarkers. In the patient with atrophic gastritis, cellular respiration was high
      and ATP was relatively low, suggesting uncoupling oxidative phosphorylation. In
      the second cohort of patients, the examined biopsies showed either normal or
      superficial gastritis. The rate of cellular respiration (O2. MUmol/L min(-1) mg(
      1)) was slightly higher in the corpus than the antrum (0.18 +/- 0.05 vs 0.15 +/-
      0.04, P = 0.019). The value of GSH was about the same in both tissues (310 +/-
      135 vs 322 +/- 155, P = 0.692). CONCLUSION: The corpus mucosa was metabolically
      more active than the antrum tissue. The data in this study will help in
      understanding the pathophysiology of gastric mucosa.

PMID- 25593496
TI  - Seven-day quintuple regimen as a rescue therapy for Helicobacter pylori
      eradication.
AB  - AIM: To determine the efficacy of two quintuple regimens for eradication of
      Helicobacter pylori (H. pylori) in patients who failed previous therapies.
      METHODS: This prospective, open-label, randomized controlled trial was a phase II
      study conducted from April 2011 to March 2012 at the Gastrointestinal and Liver
      Diseases Research Center in Rasht, Iran. A total of 208 patients with dyspepsia
      who failed previous H. pylori eradication with a ten-day quadruple therapy were
      enrolled. A random block method was used to assign patients to one of two
      treatment groups. Patients in the first group were treated with 240 mg bismuth
      subcitrate, 20 mg omeprazole, 1000 mg amoxicillin, 500 mg clarithromycin and 500
      mg tinidazole (BOACT group). Patients in the second group received a regimen
      containing 240 mg bismuth subcitrate, 20 mg omeprazole, 500 mg tetracycline, 500
      mg metronidazole and 200 mg ofloxacin (BOTMO group). Both regimens were given
      twice daily for a duration of seven days. The eradication was confirmed by a
      (14)C urea breath test 12 wk after completion of therapy. Patient compliance and
      drug side effects were evaluated at the end of the treatment period. The success
      rates were calculated by intention-to-treat and per-protocol analyses. RESULTS: A
      total of 205 patients completed the course of treatment, with three patients
      excluded due to drug intolerance. The mean age of patients did not differ between
      the BOACT and BOTMO groups (41.6 +/- 12.2 years vs 39.6 +/- 11.8 years), and no
      significant differences were found between the two groups in terms of age, sex,
      smoking habits or the initial eradication regimen. The intention-to-treat and per
      protocol eradication rates were significantly higher in the BOTMO group (86.5%,
      95%CI: 0.85-0.87 and 86.7%, 95%CI: 0.80-0.89, respectively) compared with the
      BOACT group (75.5%, 95%CI: 0.73-0.76 and 76%, 95%CI: 0.69-0.80, respectively) (P
      < 0.05). Univariate analyses for both groups did not show any association of sex,
      smoking and initial therapeutic regimen with eradiation rate (P > 0.05 for all).
      Significantly more patients experienced side effects in the BOACT group compared
      to the BOTMO group (77.4% vs 36.6%, P < 0.01). This difference was exemplified by
      increases in headache and taste disturbance (P < 0.05). CONCLUSION: Quintuple
      therapy with a BOTMO regimen is an alternative second-line rescue therapy for
      Iranian patients with failed first-line eradication treatment of H. pylori.

PMID- 25593499
TI  - Rare case of intussusception in an adult with acute myeloid leukemia.
AB  - Intussusception is rarely reported in adult patients with acute leukemia. We
      report a case of intussusception in a 29-year-old woman with acute myeloid
      leukemia (AML). She developed right lower quadrant pain, fever, and vomiting on
      day 16 of induction chemotherapy. Physical examination showed tenderness and
      guarding at the right lower quadrant of the abdomen. Abdominal computed
      tomography (CT) showed distension of the cecum and ascending colon, which were
      filled with loops of small bowel, and herniation of the ileocecal valve into the
      cecum. We proceeded to laparotomy and revealed ileocecal intussusception with the
      ileocecal valve as the leading point. The terminal ileum was thickened and
      invaginated into the cecum, which showed gangrenous changes. Right hemicolectomy
      was performed and microscopic examination of the colonic tissue showed
      infiltration of leukemic cells. The patient recovered after the operation and was
      subsequently able to continue treatment for AML. This case demonstrates that the
      diagnosis of intussusception is difficult because the presenting symptoms can be
      non-specific, but abdominal CT can be informative for preoperative diagnosis.
      Resection of the involved bowel is recommended when malignancy is suspected or
      confirmed. Intussusception should be considered in any leukemia patients
      presenting with acute abdomen. A high index of clinical suspicion is important
      for early diagnosis. 

PMID- 25593497
TI  - Biopathologic features and clinical significance of micrometatasis in the lymph
      node of early gastric cancer.
AB  - AIM: To evaluate the biopathologic features and clinical significance of nodal
      micrometastasis (MI) in early gastric cancer (EGC). METHODS: Among 1022 EGC
      patients who underwent gastrectomy with lymphadenectomy of D1 + beta or more from
      March 2001 to December 2005 at the Korean National Cancer Center, available nodal
      metastasis was found in 90 pT1N1 patients. Nodal metastasis was confirmed by
      immunohistochemistry (IHC) with cytokeratin and patients were classified into MI
      and macrometastasis (MA) groups based on the main tumor burden according to the
      6(th) International Union Against Cancer/American Joint Committee on Cancer
      staging system; the main tumor burden with a diameter of greater than 0.2 mm but
      no greater than 2 mm as MI, and greater than 2 mm as MA of the representative
      metastatic node. Proliferative and apoptotic activities of the primary tumor and
      the nodal metastasis were measured by IHC with Ki-67 and terminal
      deoxynucleotidyl transferase dUTP nick end labeling, respectively. Biopathologic
      and clinical features of the patients were analyzed and compared between MI and
      MA groups. Patients with recurrence were compared with those without recurrence
      to identify risk factors for recurrence. RESULTS: Thirty-seven patients showed MI
      and the other 53 patients revealed MA in the lymph node; the incidence of
      patients with MI and MA was 41.1% and 58.9%. The main tumor burden was 0.9 and
      4.6 mm in the representative metastatic node, respectively. Japanese N2 stations
      were more frequently involved in MA group (20.9%) than in MI group (10.3%) but
      the difference was not statistically different (P = 0.338). Proliferative and
      apoptotic activities of MI were decreased than those of MA (26.7% vs 40.5%, P =
      0.004 and 1.0% vs 3.0%, P < 0.001, respectively). However, nodal MI in the
      current study showed a relatively high proliferative activity and an equivalent
      apoptotic activity compared to other cancers in the previously published studies.
      Recurrence was observed in 6 patients during the mean follow up period of 87.6 +/
      26.2 mo. The recurrence was significantly associated with the presence of MA (P
      = 0.041) and lymphovascular invasion of the primary tumor (P = 0.032).
      CONCLUSION: Lymphadenectomy of D1 + beta or more might be necessary in patients
      with MI in sentinel node to prevent recurrence by clearing MI involving Japanese
      N2 station.

PMID- 25593500
TI  - Locally advanced undifferentiated carcinoma with osteoclast-like giant cells of
      the pancreas.
AB  - Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas
      (UCOGCP) is an unusual pancreatic neoplasm that represents < 1% of all pancreatic
      malignancies. Moreover, the giant cells of UCOGCP morphologically resemble the
      benign giant cells of bone tumors. Due to the rarity of this tumor type, the
      histogenesis and biologic behavior of UCOGCP remain controversial. Here, we
      report a case of UCOGCP that exhibited an invasive growth pattern involving
      infiltration of the adjacent bowel loop and portal vein, as well as superior
      mesenteric vein thrombosis. The patient underwent a distal pancreatectomy with
      splenectomy and partial colectomy, followed by four cycles of gemcitabine
      chemotherapy. No evidence of recurrence was detected after ten years. In addition
      to this case, clinical information on other UCOGCP cases reported in the English
      literature is summarized. 

PMID- 25593501
TI  - Novel mutation in a Chinese patient with progressive familial intrahepatic
      cholestasis type 3.
AB  - Genotyping is conclusive for the diagnosis of progressive familial intrahepatic
      cholestasis type 3 (PFIC3). Here we report a Chinese patient of PFIC3 with
      compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old
      male patient with intrahepatic cholestasis of unknown etiology. Liver histology
      findings are indicative of intrahepatic cholestasis with extensive fibrosis.
      Genotyping revealed c.175C>T (p.L59L) mutation in exon 4, c.504C>T (p.N168N)
      mutation in exon 6, c.711A>T (p.I237I) mutation in exon 8, c.874A>T (p.K292X) in
      exon 9 and a novel mutation, c.1804G>T (p.G602W) in exon 15. Based on these
      findings, the patient was diagnosed with PFIC3. The novel mutation p.G602W in
      exon 15 was predicted as probably damaging by PolyPhen-2 with a score of 0.986
      (sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein
      function with a SIFT score of 0.01. 

PMID- 25593498
TI  - Accurate definition and management of idiopathic sclerosing encapsulating
      peritonitis.
AB  - AIM: To review the literature on idiopathic sclerosing encapsulating peritonitis
      (SEP), also known as abdominal cocoon syndrome. METHODS: The PubMed, MEDLINE,
      Google Scholar, and Google databases were searched using specific key words to
      identify articles related to idiopathic SEP. These key words were "sclerosing
      encapsulating peritonitis," "idiopathic sclerosing encapsulating peritonitis,"
      "abdominal cocoon," and "abdominal cocoon syndrome." The search included letters
      to the editor, case reports, review articles, original articles, and meeting
      presentations published in the English-language literature from January 2000 to
      May 2014. Articles or abstracts containing adequate information about age, sex,
      symptom duration, initial diagnosis, radiological tools, and surgical approaches
      were included in the study. Papers with missing or inadequate data were excluded.
      RESULTS: The literature search yielded 73 articles on idiopathic (primary) SEP
      published in 23 countries. The four countries that published the greatest number
      of articles were India (n = 21), Turkey (n = 14), China (n = 8) and Nigeria (n =
      3). The four countries that reported the greatest number of cases were China (n =
      104; 53.88%), India (n = 35; 18.13%), Turkey (n = 17; 8.80%) and Nigeria (n = 5;
      2.59%). The present study included 193 patients. Data on age could be obtained
      for 184 patients (range: 7-87 years; mean +/- SD, 34.7 +/- 19.2 years), but were
      unavailable for nine patients. Of the 184 patients, 122 were male and 62 were
      female; sex data could not be accessed in the remaining nine patients. Of the 149
      patients whose preoperative diagnosis information could be obtained, 65 (43.6%)
      underwent operations for abdominal cocoon, while the majority of the remaining
      patients underwent operations for a presumed diagnosis of intestinal obstruction
      and/or abdominal mass. Management information could be retrieved for 115
      patients. Of these, 68 underwent excision + adhesiolysis (one laparoscopic); 24
      underwent prophylactic appendectomy in addition to excision + adhesiolysis.
      Twenty patients underwent various resection and repair techniques along with
      excision + adhesiolysis. The remaining three patients were managed with
      antituberculosis therapy (n = 2) and immunosuppressive therapy (n = 1).
      CONCLUSION: Idiopathic SEP is a rare disorder characterized by frequently
      recurring bouts of intestinal obstruction. Surgical therapy is the gold standard
      management strategy.

PMID- 25593502
TI  - Inflammatory pseudotumor of the colon causing intussusception: a case report and
      literature review.
AB  - Inflammatory pseudotumor (IPT) is a rare space-occupying lesion of unknown
      etiology that can mimic malignancy on clinic-radiological and pathological
      examination. We describe a rare case of ileocecal intussusception from clinically
      suspected malignancy of the right colon where the patient underwent right
      hemicolectomy. Histopathology of the resected specimen confirmed IPT of the
      colon. This patient was observed to have abnormally elevated total leukocyte
      count and platelets before and after surgery. In an adult with intussusception
      associated with an abdominal mass, the possibility of IPT of the colon should be
      considered. Considering the abnormally high total leukocyte and platelet counts
      and colonic IPT, it is necessary to prevent postoperative adverse effects due to
      these changes. Although IPT of the colon is usually a benign process, controversy
      regarding its management still exists. We consider hemicolectomy as a safe
      treatment approach for colonic IPT and review the existing literature. 

PMID- 25593503
TI  - Reciprocal Pathways Between Autonomous Motivation and Affect: A Longitudinal
      Investigation of American and Chinese Early Adolescents.
AB  - The current research examined the reciprocal pathways between children's
      autonomous motivation in school and affect over early adolescence in the United
      States and China. Beginning in the fall of 7th grade, 825 American and Chinese
      children (mean age = 12.73 years) reported on their autonomous (vs. controlled)
      motivation as well as unpleasant and pleasant affect every six months until the
      end of eighth grade. In both the United States and China, there were negative
      reciprocal pathways between children's autonomous motivation and unpleasant
      affect: Over time, heightened autonomous motivation predicted dampened unpleasant
      affect, which in turn predicted heightened autonomous motivation. Positive
      reciprocal pathways between children's autonomous motivation and pleasant affect
      were evident over time only in China.

PMID- 25593504
TI  - Induction of endothelial RAGE expression in pterygium.
AB  - PURPOSE: Chronic inflammation is a critical process in pterygium development and
      progression, including promotion of angiogenesis. Vascular endothelial cells
      (ECs) actively participate in and regulate inflammation. Pterygium research has
      uncovered multiple inflammatory cytokines that are upregulated, but there has
      been minimal focus on EC activation. The Receptor for Advanced Glycation
      Endproducts (RAGE), a major proinflammatory molecule expressed in the vascular
      endothelium and other cell types, is a major instigator of endothelial cell
      activation. In this study, we explored the hypothesis that RAGE is upregulated in
      ECs in pterygium. To this end, we examined RAGE expression and immunolocalization
      in human pterygium and normal conjunctival tissue, with a particular interest in
      assessing endothelial RAGE. METHODS: Pterygium specimens were obtained from 25
      patients during surgery at the King Khaled Eye Specialist Hospital (KKESH). In
      the same patients, conjunctiva were obtained from the autograft during surgery.
      Tissue specimens were formalin-fixed and paraffin-embedded. Tissue sections were
      analyzed with immunohistochemistry with anti-RAGE antibody. Expression and
      localization of RAGE were evaluated in pterygium and corresponding conjunctiva.
      RESULTS: RAGE expression was detected in the vascular endothelium in all
      pterygium tissue specimens and most conjunctival specimens. Other cell types
      exhibited expression, notably epithelial cells, fibroblasts, and possibly
      macrophages. Strikingly, endothelial RAGE expression was increased in 19 of 25
      pterygium tissue specimens, compared to the corresponding control conjunctiva.
      CONCLUSIONS: Our data reveal that RAGE expression is upregulated in vascular
      endothelial cells in pterygium. RAGE upregulation is an important mechanism by
      which endothelial cells amplify the overall inflammatory response, and
      suppression of RAGE has been shown to prevent the progression of some systemic
      disease processes in experimental models. This suggests that pharmacologic
      targeting of RAGE, which is already being attempted in clinical trials for some
      diseases, could be useful in treating pterygium.

PMID- 25593505
TI  - Lenticular cytoprotection, part 2: link between glycogen synthase kinase-3beta,
      epithelial to mesenchymal transition, and mitochondrial depolarization.
AB  - PURPOSE: The inhibition of GSK-3beta blocks mitochondrial membrane permeability
      transition (mMPT) for HLE-B3 cells in atmospheric oxygen. GSK-3beta, as part of a
      multifactorial complex, also regulates nuclear levels of beta-catenin, a known
      coordinator of cell survival and adhesion. The purpose of these studies was to
      demonstrate a novel, but likely disadvantageous, link between beta-catenin's
      influence on the expression of the pro-survival protein, vascular endothelial
      growth factor (VEGF), resulting in enhanced lens epithelial cell mitochondrial
      protection against depolarization and nuclear beta-catenin as an inducer of
      epithelial to mesenchymal transition (EMT). METHODS: Virally transformed human
      lens epithelial cells (HLE-B3) were treated with SB216763, a specific inhibitor
      of GSK-3beta catalytic activity and XAV939, a specific beta-catenin inhibitor
      that bars the translocation of beta-catenin from cytoplasm to the nucleus.
      Western blot analysis was employed to detect the levels of cytoplasmic and
      nuclear beta-catenin and phospho-beta-catenin, pBcl-2 and the EMT proteins, alpha
      smooth muscle actin (alpha-SMA), and fibronectin. ELISA was used to measure the
      levels of VEGF in cell culture supernatants. JC-1 analysis was performed to
      analyze the influence of either SB216763 or XAV939 on mitochondrial
      depolarization. RESULTS: Cultured lens epithelial cells maintained in hypoxia (1%
      oxygen) and subsequently reintroduced into atmospheric oxygen and treated with
      the GSK-3beta inhibitor SB216763 illustrated a marked inhibition of
      phosphorylation of glycogen synthase (downstream substrate of GSK-3beta) and
      significant increase in nuclear translocation of beta-catenin. The augmented
      nuclear beta-catenin levels positively correlated with increased expression of
      alpha-SMA and fibronectin, both marker proteins indicative of EMT. The enhanced
      nuclear beta-catenin activity also elicited increased VEGF and pBcl-2 expression,
      resulting in increased resistance to mitochondrial depolarization. Treatment of
      the cells with the beta-catenin inhibitor XAV939 resulted in decreased expression
      of nuclear beta-catenin, VEGF levels, pBcl-2, and EMT proteins, as well as
      increased mitochondrial depolarization. CONCLUSIONS: The data support a model
      whereby the onset of epithelial to mesenchymal transition may circuitously
      benefit from the enhanced synthesis of VEGF by setting up a potentially harmful
      situation whereby the resulting mesenchymal cell population may be more resistant
      to mitochondrial depolarization than the lens epithelial cell population from
      which it originated. These findings support the potential therapeutic relevance
      of developing strategies to undermine the progression of normal cells to
      mesenchymal transition without subverting cell viability.

PMID- 25593507
TI  - Neuroprotective effect of astaxanthin against rat retinal ganglion cell death
      under various stresses that induce apoptosis and necrosis.
AB  - PURPOSE: Astaxanthin is a type of carotenoid known to have strong antioxidant
      effects. The purpose of this study was to investigate whether astaxanthin confers
      a neuroprotective effect against glutamate stress, oxidative stress, and hypoxia
      induced apoptotic or necrotic cell death in primary cultures of rat retinal
      ganglion cells (RGCs). METHODS: Purified rat RGCs were exposed to three kinds of
      stressors induced by 25 MUM glutamate for 72 h, B27 medium without an antioxidant
      for 4 h, and a reduced oxygen level of 5% for 12 h. Each assay was repeated 12
      times, with or without 1 nM, 10 nM, and 100 nM astaxanthin. The number of live
      RGCs was then counted using a cell viability assay. RGC viability in each
      condition was evaluated and compared with controls. In addition, we measured
      apoptosis and DNA damage. RESULTS: We found that under glutamate stress, RGC
      viability was reduced to 58%. Cultures with 1 nM, 10 nM, and 100 nM astaxanthin
      showed an increase in RGC viability of 63%, 74%, and 84%, respectively. Under
      oxidative stress, RGC viability was reduced to 40%, and astaxanthin
      administration resulted in increased viability of 43%, 50%, and 67%,
      respectively. Under hypoxia, RGC viability was reduced to 66%, and astaxanthin
      administration resulted in a significant increase in viability to 67%, 77%, and
      93%, respectively. These results indicate that 100 nM astaxanthin leads to a
      statistically significant increase in RGC viability under the three kinds of
      stressors tested, compared to controls (Dunnett's test, p<0.05). The apoptotic
      activity of RGCs under glutamate stress increased to 32%, but was reduced to 15%
      with 100 nM astaxanthin administration. Glutamate stress led to a 58% increase in
      DNA damage, which was reduced to 43% when cultured with 100 nM astaxanthin. Thus,
      100 nM astaxanthin showed a statistically significant reduction in apoptosis and
      DNA damage in RGCs (Wilcoxon rank-sum test, p<0.05). CONCLUSIONS: Our results
      suggest that astaxanthin has a neuroprotective effect against RGC death induced
      by glutamate stress, oxidative stress, and hypoxia, which induce apoptotic and
      necrotic cell death.

PMID- 25593506
TI  - Basal membrane complex architecture is disrupted during posterior subcapsular
      cataract formation in Royal College of Surgeons rats.
AB  - PURPOSE: Previous studies detailing the development of posterior subcapsular
      cataracts (PSC) in Royal College of Surgeons (RCS) rats have shown that aberrant
      fiber-end migration underlies the structural compromise. This investigation was
      conducted to examine the distribution of select basal membrane complex (BMC)
      components and to assess the intravitreal levels of specific cytokines during PSC
      formation. METHODS: Lenses from 52 RCS dystrophic rats (RCS/Lav) and 28
      genetically matched control animals (RCS-rdy(+)/Lav) from 2 to 8 weeks old were
      used. After enucleation, vitreous was collected for eventual cytokine level
      analyses; lenses were then removed and processed for immunocytochemical
      localization of actin, cadherin, beta integrin, vinculin, and cell nuclei.
      RESULTS: At 2-3 weeks postnatal, dystrophic lenses showed normal BMC distribution
      of actin, cadherin, and vinculin; however beta integrin distribution was altered
      as compared to controls. By 4-6 weeks of age, F-actin was visible as bright foci
      arranged in a "rosette" pattern around fiber-end profiles. Concurrently, vinculin
      was rearranged into a diffuse pattern within the BMC. Cadherin delineated the
      fiber ends in dystrophic lenses until 5 weeks postnatal, after which it displayed
      diffuse cytoplasmic staining with more definitive labeling at the BMC periphery.
      beta integrin was initially distributed as punctuate spots at 2-3 weeks
      postnatal; however, by 4-6 weeks it was co-localized with F-actin around the
      periphery of fiber ends. The distribution of F-actin, cadherin, and beta integrin
      components did not undergo further changes after 6 weeks of age; however,
      vinculin was present predominantly at the periphery of the BMC in 7-8-week-old
      dystrophic lenses. Intravitreal cytokine levels were assessed for interleukin
      (IL)-1alpha, IL-4, IL-6, IL-8, tumor necrosis factor (TNF), and interferon (IFN)
      gamma. Levels of IL-1alpha, IL-4, TNF, and IFN-gamma demonstrated a similar
      pattern, with concentrations increasing from 2 to 6 weeks postnatal and then
      decreasing slightly up to 8 weeks of age. IL-4 and TNF had the highest average
      concentrations, with peaks of 148.00 pg/ml and 34.20 pg/ml, respectively.
      CONCLUSIONS: The data indicate that defined rearrangements of normal BMC
      architecture precede and characterize the structural changes that culminate in
      the PSC. These are consistent with modifications of adhesion mechanics involving
      cell-cell attachment, cell-matrix adhesion, and timely fiber-end detachment.
      Further, the results suggest that pro-inflammatory cytokines are potential
      initiating factors in aberrant fiber-end migration and subsequent PSC formation.

PMID- 25593508
TI  - Identification of novel CYP4V2 gene mutations in 92 Chinese families with
      Bietti's crystalline corneoretinal dystrophy.
AB  - PURPOSE: To characterize the spectrum of CYP4V2 gene mutations in 92 unrelated
      Chinese probands with Bietti's crystalline dystrophy (BCD) and to describe the
      molecular and clinical characteristics of four novel CYP4V2 mutations associated
      with BCD. METHODS: All study participants underwent a complete ophthalmological
      examination. Mutational screening of CYP4V2 coding regions and flanking intron
      sequences was examined via directional Sanger sequencing, with allele separation
      confirmed by screening other family members. Subsequent in silico analysis of the
      mutational consequence on protein function was undertaken, with the impact of the
      novel mutation on pre-mRNA splicing examined via RT-PCR. RESULTS: Fifteen disease
      causing variants were identified in 92 probands with BCD, including four novel
      mutations and eleven previously reported mutations. The most prevalent mutation
      was c.802_810del17insGC, which was detected in 69 unrelated families, with an
      allele frequency of 52.7% (97/184). Homozygosity was revealed in 35 unrelated
      families, and compound heterozygosity was observed in 43 subjects. Four patients
      harbored four novel variants, with these mutations cosegregated within all
      affected individuals and were not found in unaffected family members and 100
      unrelated controls. Transcriptional analysis of a novel splice mutation revealed
      altered RNA splicing. In silico analysis predicted that the missense variant,
      p.Tyr343Asp, disrupted the CYP4V2 surface electrostatic potential distribution
      and spatial conformation. Among the patients with four novel mutations, genotype
      did not always correlate with age at onset, disease course, or electroretinogram
      (ERG) changes, with phenotypic variations even noted within the same genotype.
      CONCLUSIONS: The c.802_810del17insCG mutation was the most common mutation in the
      92 Chinese probands with BCD examined. Four novel mutations were identified,
      contributing to the spectrum of CYP4V2 mutations associated with BCD, with no
      clear link established between disease phenotype and genotype.

PMID- 25593509
TI  - The effect of puerarin against IL-1beta-mediated leukostasis and apoptosis in
      retinal capillary endothelial cells (TR-iBRB2).
AB  - PURPOSE: Blood-retinal barrier (BRB) breakdown, the early hallmark of diabetic
      retinopathy (DR), is thought to depend on retinal inflammation and cell damage.
      The proinflammatory factor interleukin-1beta (IL-1beta) was demonstrated to cause
      inflammation as well as cell apoptosis during the process of BRB breakdown. This
      study extensively evaluated the protective effect of puerarin, a major active
      component extracted from the traditional herb Radix puerariae, against IL-1beta
      induced cell dysfunction in TR-iBRB2 cells, a retinal capillary endothelial cell
      line. METHODS: TR-iBRB2 cells were pretreated with IL-1beta (10 ng/ml) for 24 h
      and then exposed to puerarin (0, 10, 25, and 50 MUM) for another 24 h. Leukocyte
      endothelial adhesion was assessed through a cell-based assay using lymphoblastoid
      cells. Cell apoptosis was evaluated with flow cytometry, and the expression of
      adhesion molecules and apoptosis-related molecules was assessed with western blot
      analysis. RESULTS: Our data showed that puerarin attenuated IL-1beta-mediated
      leukostasis and cell apoptosis in TR-iBRB2 cells. Furthermore, puerarin
      strikingly prevented IL-1beta-induced molecular events of the upstream and
      downstream signaling pathways involved in this cellular process. CONCLUSIONS:
      These findings may significantly contribute to better understanding of the
      protective effect of puerarin, in particular for DR, as well as provide novel
      insights into the potential application of this compound in DR therapy.

PMID- 25593510
TI  - Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient
      corneal epithelium corresponds to disease severity.
AB  - PURPOSE: Keratoconus (KC) is characterized by progressive vision loss due to
      corneal thinning and structural abnormalities. It is hypothesized that KC is
      caused by deregulated collagen levels and collagen fibril-maturating enzyme lysyl
      oxidase (LOX). Further, it is currently not understood whether the gene
      expression deregulated by the corneal epithelium influences KC pathogenesis. We
      studied (i) the expressions of the LOX, collagen I (COL IA1), collagen IV (COL
      IVA1), MMP9, and IL6 genes in KC corneal epithelia, (ii) validated their
      expression levels in patient tissues, and (iii) correlated expression levels with
      KC disease severity. The primary goal of this study was to evaluate the
      importance of these genes in the progression of KC. METHODS: We analyzed the gene
      expression levels of the key proteins LOX, collagens (COL IA1 and COL IVA1),
      MMP9, and IL6 in debrided corneal epithelia from a large cohort of KC patients
      (90 eyes) and compared them to control patients (52 eyes) without KC. We measured
      the total LOX activity in the tears of KC patients compared to controls. We also
      correlated the protein expression levels of LOX and collagens by
      immunohistochemistry (IHC) in primary tissues from KC patients (27 eyes)
      undergoing keratoplasty compared to healthy donor corneas (15 eyes). RESULTS: We
      observed a significant reduction in LOX transcript levels in KC corneal
      epithelia, and LOX activity in KC tears correlated with disease severity.
      Collagen transcripts were also reduced in KC while MMP9 transcript levels were
      upregulated and correlated with disease severity. IL6 was moderately increased in
      KC patients. IHC demonstrated a reduction in the protein expression levels of LOX
      in the epithelium and collagen IV in the basement membrane of KC patients
      compared to healthy donor corneas. CONCLUSIONS: The data demonstrates that the
      structural deformity of the KC cornea may be dependent on reduced expressions of
      collagens and LOX, as well as on MMP9 elevated by the corneal epithelium.

PMID- 25593511
TI  - Transcriptional regulation of crystallin, redox, and apoptotic genes by C
      Phycocyanin in the selenite-induced cataractogenic rat model.
AB  - PURPOSE: This study was designed to examine the constrictive potential of C
      Phycocyanin (C-PC) in regulating changes imposed on gene expression in the
      selenite-induced cataract model. METHODS: Wistar rat pups were divided into three
      groups of eight each. On P10, Group I received an intraperitoneal injection of
      normal saline. Groups II and III received a subcutaneous injection of sodium
      selenite (19 MUmol/kg bodyweight); Group III also received an intraperitoneal
      injection of C-PC (200 mg/kg bodyweight) on P9-14. Total RNA was isolated on P16,
      and the relative abundance of mRNA of the crystallin structural genes, redox
      components, and apoptotic cascade were ascertained with real-time PCR with
      reference to the internal control beta-actin. RESULTS: Real-time PCR analysis
      showed the crystallin genes (alphaA-, betaB1-, gammaD-) and redox cycle
      components (Cat, SOD-1, Gpx) were downregulated, the apoptotic components were
      upregulated, and antiapoptotic Bcl-2 was downregulated in Group II. Treatment
      with 200 mg/kg bodyweight C-PC (Group III) transcriptionally regulated the
      instability of the expression of these genes, thus ensuring C-PC is a prospective
      anticataractogenic agent that probably delays the onset and progression of
      cataractogenesis induced by sodium selenite. CONCLUSIONS: C-PC treatment possibly
      prevented cataractogenesis triggered by sodium selenite, by regulating the lens
      crystallin, redox genes, and apoptotic cascade mRNA expression and thus maintains
      lens transparency. C-PC may be developed as a potential antioxidant compound
      applied in the future to prevent and treat age-related cataract.

PMID- 25593514
TI  - Does implied community size predict likeability of a similar stranger?
AB  - Homophily, the tendency for people to cluster with similar others, has primarily
      been studied in terms of proximal, psychological causes, such as a tendency to
      have positive associations with people who share traits with us. Here we
      investigate whether homophily could be correlated with perceived group
      membership, given that sharing traits with other people might signify membership
      of a specific community. In order to investigate this, we tested whether the
      amount of homophily that occurs between strangers is dependent on the number of
      people they believe share the common trait (i.e. the size of group that the trait
      identifies). In two experiments, we show that more exclusive (smaller) groups
      evoke more positive ratings of the likeability of a stranger. When groups appear
      to be too inclusive (i.e. large) homophily no longer occurs, suggesting that it
      is not only positive associations with a trait that cause homophily, but a sense
      of the exclusiveness of a group is also important. These results suggest that
      group membership based on a variety of traits can encourage cohesion between
      people from diverse backgrounds, and may be a useful tool in overcoming
      differences between groups.

PMID- 25593513
TI  - Someone to live for: effects of partner and dependent children on preventable
      death in a population wide sample from Northern Ireland.
AB  - How to allocate resources between somatic maintenance and reproduction in a
      manner that maximizes inclusive fitness is a fundamental challenge for all
      organisms. Life history theory predicts that effort put into somatic maintenance
      (health) should vary with sex, mating and parenting status because men and women
      have different costs of reproduction, and because life transitions such as family
      formation alter the fitness payoffs from investing in current versus future
      reproduction. However, few tests of how such life history parameters influence
      behaviours closely linked to survival exist. Here we examine whether specific
      forms of preventable death (accidents/suicides, alcohol-related causes, and other
      preventable diseases) are predicted by marital status and dependent offspring in
      a modern developed context; that of Northern Ireland. We predict that men, non
      partnered individuals and individuals who do not have dependent offspring will be
      at higher risk of preventable death. Running survival analyses on the entire
      adult population (aged 16-59, n = 927,134) controlling for socioeconomic position
      (SEP) and other potential confounds, we find that being single (compared to
      cohabiting/married) increases risk of accidental/suicide death for men (but not
      for women), whereas having dependent children is associated with lower risk of
      preventable mortality for women but less so for men. We also find that the
      protective effect of partners is larger for men with low SEP than for high SEP
      men. Findings support life history predictions and suggest that individuals
      respond to variation in fitness costs linked to their mating and parenting
      status.

PMID- 25593515
TI  - [Bias in the enumeration of single marital status for females in population
      censuses: a proposal for correction.]
AB  - This paper investigates the effect of consensual union dissolution on the
      observed levels of women never in union as estimated from the marital status
      variable in Latin American population censuses. We compare census data with data
      from Demographic and Health Surveys (DHS) for those countries and years where
      both sources are available (Bolivia, Brazil, Colombia, and Peru). Results show
      that the proportions of women never in union based on the census 'marital status'
      variable are systematically higher than those estimated from the DHS. This
      overestimation is due to individuals formerly in consensual unions declaring
      themselves as single at the time of the census. The large proportion of single
      women that have children is strong evidence of this and at the same time appears
      to be a valid and practical option to correct the bias.

PMID- 25593512
TI  - Methodologies for analysis of patterning in the mouse RPE sheet.
AB  - PURPOSE: Our goal was to optimize procedures for assessing shapes, sizes, and
      other quantitative metrics of retinal pigment epithelium (RPE) cells and contact-
      and noncontact-mediated cell-to-cell interactions across a large series of
      flatmount RPE images. METHODS: The two principal methodological advances of this
      study were optimization of a mouse RPE flatmount preparation and refinement of
      open-access software to rapidly analyze large numbers of flatmount images. Mouse
      eyes were harvested, and extra-orbital fat and muscles were removed. Eyes were
      fixed for 10 min, and dissected by puncturing the cornea with a sharp needle or a
      stab knife. Four radial cuts were made with iridectomy scissors from the puncture
      to near the optic nerve head. The lens, iris, and the neural retina were removed,
      leaving the RPE sheet exposed. The dissection and outcomes were monitored and
      evaluated by video recording. The RPE sheet was imaged under fluorescence
      confocal microscopy after staining for ZO-1 to identify RPE cell boundaries.
      Photoshop, Java, Perl, and Matlab scripts, as well as CellProfiler, were used to
      quantify selected parameters. Data were exported into Excel spreadsheets for
      further analysis. RESULTS: A simplified dissection procedure afforded a
      consistent source of images that could be processed by computer. The dissection
      and flatmounting techniques were illustrated in a video recording. Almost all of
      the sheet could be routinely imaged, and substantial fractions of the RPE sheet
      (usually 20-50% of the sheet) could be analyzed. Several common technical
      problems were noted and workarounds developed. The software-based analysis merged
      25 to 36 images into one and adjusted settings to record an image suitable for
      large-scale identification of cell-to-cell boundaries, and then obtained
      quantitative descriptors of the shape of each cell, its neighbors, and
      interactions beyond direct cell-cell contact in the sheet. To validate the
      software, human- and computer-analyzed results were compared. Whether tallied
      manually or automatically with software, the resulting cell measurements were in
      close agreement. We compared normal with diseased RPE cells during aging with
      quantitative cell size and shape metrics. Subtle differences between the RPE
      sheet characteristics of young and old mice were identified. The IRBP(-/-) mouse
      RPE sheet did not differ from C57BL/6J (wild type, WT), suggesting that IRBP does
      not play a direct role in maintaining the health of the RPE cell, while the slow
      loss of photoreceptor (PhR) cells previously established in this knockout does
      support a role in the maintenance of PhR cells. Rd8 mice exhibited several
      measurable changes in patterns of RPE cells compared to WT, suggesting a slow
      degeneration of the RPE sheet that had not been previously noticed in rd8.
      CONCLUSIONS: An optimized dissection method and a series of programs were used to
      establish a rapid and hands-off analysis. The software-aided, high-sampling-size
      approach performed as well as trained human scorers, but was considerably faster
      and easier. This method allows tens to hundreds of thousands of cells to be
      analyzed, each with 23 metrics. With this combination of dissection and image
      analysis of the RPE sheet, we can now analyze cell-to-cell interactions of
      immediate neighbors. In the future, we may be able to observe interactions of
      second, third, or higher ring neighbors and analyze tension in sheets, which
      might be expected to deviate from normal near large bumps in the RPE sheet caused
      by druse or when large frank holes in the RPE sheet are observed in geographic
      atrophy. This method and software can be readily applied to other aspects of
      vision science, neuroscience, and epithelial biology where patterns may exist in
      a sheet or surface of cells.

PMID- 25593516
TI  - Good doctors and the State of Missouri: a connection worth remembering.

PMID- 25593517
TI  - Therapeutic listening.

PMID- 25593518
TI  - Repeated transradial catheterization: feasibility, efficacy, and safety.
AB  - Transradial access is an alternative to the transfemoral approach in coronary
      interventions. It results in less access-site bleeding, shorter hospital stays,
      lower costs, and less pain for the patient. However, some authors have suggested
      that the transradial approach might lead to radial artery occlusion, which
      precludes repeated same-artery catheterizations. Using data from our center, we
      evaluated the feasibility, safety, and efficacy of repeated transradial
      catheterization. We reviewed the 3,006 transradial catheterizations performed at
      our center from 2006 through 2009. Patients who had undergone at least one
      repeated transradial catheterization were identified, their cases monitored
      through 2012, and their baseline characteristics and other factors, including
      procedural sequelae, were analyzed. Seventy-nine patients underwent repeated
      right radial artery catheterizations, for a total of 92 repeated procedures.
      Repeated access to the right radial artery was not achieved in 4 attempts
      (failure rate, 4.3%), because of poor pulses or the operator's inability to
      advance the wire. No major sequelae were noted. The average times between the 1st
      to 2nd, 2nd to 3rd, and 3rd to 4th catheterizations were 406, 595, and 401 days,
      respectively. Our procedural success rate of 95.7% in performing repeated
      transradial catheterizations with no major sequelae provides support for the
      efficacy and safety of such procedures. 

PMID- 25593519
TI  - Current use of fractional flow reserve: a nationwide survey.
AB  - Major medical society guidelines recommend the measurement of fractional flow
      reserve (FFR) as an aid in choosing percutaneous coronary intervention in
      patients with stable coronary artery disease. We investigated the measurement of
      FFR among interventionalists, analyzing operators' attributes and decision-making
      processes to reveal differences in their applications of FFR and the reasons for
      those differences. An electronic survey study of 1,089 interventionalists was
      performed from 2 February through 6 March 2012, yielding 255 responses. Most
      respondents were >45 years old (58%), worked primarily in a community hospital
      (59%), and performed 10 to 30 cases per month (52%). More than half (145/253,
      57%) used FFR measurement in less than one third of cases, and 39 of 253 (15%)
      never used it. There were no differences in use of FFR by age, practice location,
      or angiogram volume (P >0.05 for all). Respondents used FFR measurement more
      frequently than intravascular ultrasonography (73% vs 60%) to help guide the
      decision to stent (P <0.01). Operators reported that their primary reasons for
      not using FFR were lack of availability (47%) and problems with reimbursement
      (39%). There was no difference in FFR use by operator age, practice setting, or
      case volume. 

PMID- 25593520
TI  - Aortic valve reconstruction with use of pericardial leaflets in adults with
      bicuspid aortic valve disease: early and midterm outcomes.
AB  - In this study, we retrospectively analyzed the outcomes of adults with bicuspid
      aortic valve (BAV) disease who underwent aortic valve reconstructive surgery
      (AVRS), consisting of replacement of the diseased BAV with 2 or 3 pericardial
      leaflets plus fixation of the sinotubular junction for accurate and constant
      leaflet coaptation. From December 2007 through April 2013, 135 consecutive
      patients (mean age, 49.2 +/- 13.1 yr; 73.3% men) with symptomatic BAV disease
      underwent AVRS. Raphe was observed in 84 patients (62.2%), and the remaining 51
      patients had pure BAV without raphe. A total of 122 patients (90.4%) underwent 3
      leaflet reconstruction, and 13 (9.6%) underwent 2-leaflet reconstruction.
      Concomitant aortic wrapping with an artificial graft was performed in 63 patients
      (46.7%). There were no in-hospital deaths and 2 late deaths (1.5%); 6 patients
      (4.4%) needed valve-related reoperation. The 5-year cumulative survival rate was
      98% +/- 1.5%, and freedom from valve-related reoperation at 5 years was 92.7% +/-
      3.6%. In the last available echocardiograms, aortic regurgitation was absent or
      trivial in 116 patients (85.9%), mild in 16 (11.9%), moderate in 2 (1.5%), and
      severe in one (0.7%). The mean aortic valve gradient was 10.2 +/- 4.5 mmHg, and
      the mean aortic valve orifice area index was 1.3 +/- 0.3 cm(2)/m(2). The 3
      leaflet technique resulted in lower valve gradients and greater valve areas than
      did the 2-leaflet technique. Thus, in patients with BAV, AVRS yielded
      satisfactory early and midterm results with low mortality rates and low
      reoperation risk after the initial procedure. 

PMID- 25593521
TI  - Left atrial myxoma with versus without cerebral embolism: length of symptoms,
      morphologic characteristics, and outcomes.
AB  - The aim of this study was to evaluate the embolic sequelae of left atrial myxomas
      and their influence on diagnosis, treatment, and prognosis. Seventy-eight
      patients were retrospectively investigated. According to their symptoms and
      neurologic-imaging findings, these patients were classified into 2 groups:
      embolism (15 patients, 19%) and nonembolism (63 patients, 81%). The time from the
      first onset of symptoms to diagnosis (that is, the duration of symptoms) was
      significantly longer in the embolism group than in the nonembolism group (105 +/-
      190 vs 23 +/- 18 d; P <0.01). The myxomas were divided into 2 types on the basis
      of clinicopathologic findings: type 1, with an irregular or villous surface and a
      soft consistency, and type 2, with a smooth surface and a compact consistency.
      There were 42 patients with type 1 myxoma and 36 with type 2. Type 1 myxoma was
      more frequently found in the embolism group (12 patients, 29%) than was type 2
      myxoma (3 patients, 8%). The difference was significant (P=0.04). There were 2
      perioperative deaths in the nonembolism group. No recurrence of cardiac myxoma or
      death was recorded in either group during follow-up. In the embolism group,
      neurologic symptoms were relieved by surgery, and no subsequent neurologic event
      was reported. Because surgical resection is highly effective in left atrial
      myxoma, we should strive for early diagnosis in order to shorten the duration of
      symptoms and to avoid worse neurologic damage in patients in whom an embolic
      event is the initial manifestation. 

PMID- 25593522
TI  - Brachiocephalic artery cannulation in proximal aortic surgery that requires
      circulatory arrest.
AB  - The brachiocephalic artery is an alternative cannulation site in the repair of
      ascending aortic lesions that require circulatory arrest. We evaluate the
      effectiveness and safety of this technique. Proximal aortic surgery was performed
      in 32 patients from 2006 through 2012 via brachiocephalic artery cannulation and
      circulatory arrest. Twenty-four (75%) of the patients were men. The mean age was
      48.69 +/- 9.43 years (range, 30-68 yr). Twelve had type I dissection, 2 had type
      II dissection, and 18 had true aneurysms of the ascending aorta. All operations
      were performed through a median sternotomy. The arterial cannula was inserted
      through an 8-mm vascular graft anastomosed to the brachiocephalic artery in an
      end-to-side fashion. In dissections, the distal anastomosis was performed without
      clamping the aorta. The patients were cooled to 24  degrees C, and circulatory
      arrest was established. The brachiocephalic and left carotid arteries were
      clamped, and antegrade cerebral perfusion was started at a rate of 10 mL/kg/min.
      Cardiopulmonary bypass was resumed after completion of the distal anastomosis and
      the initiation of rewarming. The proximal anastomosis was then performed. None of
      the patients sustained a major neurologic deficit, but 5 patients experienced
      transient postoperative agitation (<24 hr). There were 2 early deaths (6.25%), on
      the 3rd and the 11th postoperative days, both unrelated to the cannulation
      technique. Brachiocephalic artery cannulation through a graft can be a safe and
      effective technique in proximal aortic surgical procedures that require
      circulatory arrest. 

PMID- 25593523
TI  - Single coronary ostium in right coronary sinus: previously unreported "one for
      all" configuration.
AB  - We report our identification of a single coronary ostium arising from the right
      coronary sinus of Valsalva, in a 63-year-old woman who presented with chest pain
      atypical of angina. Coronary angiograms showed that the left anterior descending
      coronary artery arose from a right ventricular branch and that the left
      circumflex coronary artery arose from a right posterolateral branch. Both
      arteries reconstituted themselves in a backward fashion from the apex to the base
      of the heart-a configuration that to our knowledge has not been reported. The
      patient was treated conservatively and reported no chest pain 24 months later. 

PMID- 25593524
TI  - Giant coronary artery aneurysms: review and update.
AB  - Giant coronary artery aneurysms are rare, with a reported prevalence of 0.02% to
      0.2%. Causative factors include atherosclerosis, Takayasu arteritis, congenital
      disorders, Kawasaki disease, and percutaneous coronary intervention. Most giant
      coronary artery aneurysms are asymptomatic, but some patients present with angina
      pectoris, sudden death, fistula formation, pericardial tamponade, compression of
      surrounding structures, or congestive heart failure. Clinical sequelae include
      thrombus formation, embolization, fistula formation, and rupture. Surgical
      correction is generally accepted as the preferred treatment for giant coronary
      artery aneurysms. We present an illustrative case of a giant 70 * 40-mm coronary
      artery aneurysm in a 56-year-old man who declined surgery and died one month
      later. In addition, we provide a review of the medical literature on giant
      coronary artery aneurysms. 

PMID- 25593525
TI  - Mitral valve surgery in 6 patients after failed MitraClip therapy.
AB  - The MitraClip percutaneous mitral valve repair system, developed as an option for
      percutaneous mitral repair, was clinically introduced in 2007. From 2010 through
      2012, 6 of our patients underwent mitral valve surgery after MitraClip failure.
      Their mean age was 75 +/- 7.7 years (range, 62-87 yr). Three had undergone
      cardiac surgery previously. In 5 of the 6 patients, mitral regurgitation recurred
      after initially successful MitraClip deployment and was the indication for
      surgery. The mean interval between MitraClip implantation and surgery was 106 +/-
      86 days (range, 0-238 d). Mitral valve repair was feasible in 3 patients; the
      others underwent valve replacement. All the patients underwent additional cardiac
      procedures, because the MitraClip worsened existing conditions. Echocardiograms
      revealed sufficient valvular repairs. Two patients died during hospitalization,
      one of cerebral infarction and the other of bowel ischemia. Mitral valve repair
      after failed MitraClip therapy can be complex and a surgical challenge. Careful
      consideration should be given to appropriate patient selection for MitraClip
      therapy, because the MitraClip can cause existing pathologic valvular conditions
      to deteriorate substantially. The interval between MitraClip failure and
      corrective surgery should be as short as possible. The primary indication is an
      issue of ongoing discussion. 

PMID- 25593526
TI  - Percutaneous repair of post-myocardial infarction ventricular septal defect:
      current approaches and future perspectives.
AB  - Post-myocardial infarction ventricular septal defect is a devastating
      complication of ST-elevation myocardial infarction. Although surgical
      intervention is considered the gold standard for treatment, it carries high
      morbidity and mortality rates. We present 2 cases that illustrate the application
      of percutaneous closure of a post-myocardial infarction ventricular septal
      defect: the first in a patient who had undergone prior surgical closure and then
      developed a new shunt, and the second as a bridge to definitive surgery in a
      critically ill patient. 

PMID- 25593527
TI  - Ventricular tachycardia associated with radiation-induced cardiac sarcoma.
AB  - Cardiac tumors can lead to distinct electrocardiographic changes and ventricular
      arrhythmias. Benign and malignant cardiac tumors have been associated with
      ventricular tachycardia. When possible, benign tumors should be resected when
      ventricular arrhythmias are intractable. Chemotherapy can shrink malignant tumors
      and eliminate arrhythmias. We report the case of a 52-year-old woman with breast
      sarcoma whom we diagnosed with myocardial metastasis after she presented with
      palpitations. The initial electrocardiogram revealed sinus rhythm with new right
      bundle branch block and ST-segment elevation in the anterior precordial leads.
      During telemetry, hemodynamically stable, sustained ventricular tachycardia with
      right ventricular localization was detected. Images showed a myocardial mass in
      the right ventricular free wall. Amiodarone suppressed the arrhythmia. To our
      knowledge, this is the first report of ventricular tachycardia associated with
      radiation-induced undifferentiated sarcoma. We discuss the distinct
      electrocardiographic changes and ventricular arrhythmias that can be associated
      with cardiac tumors, and we review the relevant medical literature. 

PMID- 25593528
TI  - T-cell prolymphocytic leukemia with extensive cardiovascular infiltrate leading
      to multiple myocardial infarctions and cardiac death.
AB  - Lymphocytic neoplasm involving the heart is not common and usually presents with
      pericardial effusion or focal myocardial infiltration. Myocardial infarctions due
      to leukemic infiltration of the coronary arteries are rarely reported. We present
      the case of a 52-year-old Guatemalan man with a one-year history of untreated T
      cell prolymphocytic leukemia. He was admitted to our hospital for chemotherapy
      and evaluation of a pulmonary cavitary lesion by wedge resection. During
      sedation, the patient experienced acute respiratory failure and hypovolemic
      shock, from which he could not be resuscitated. Autopsy revealed that leukemic
      cells extensively infiltrated the aorta, myocardium, and coronary arteries. The
      lumina of the 3 major coronary artery branches showed 70% to 95% stenosis, with
      multifocal remote myocardial infarctions. Tumor cells were also detected in the
      lungs and other organs. The acute cardiorespiratory insufficiency secondary to
      leukemia-particularly the extensive infiltration of the coronary arteries and
      myocardium, and the multiple myocardial infarctions-eventually resulted in
      cardiac death. 

PMID- 25593529
TI  - Exercise-induced syncope in a sedentary woman.
AB  - Vasovagal (neurocardiogenic) syncope, a subtype of reflex syncope, has many well
      known triggers. However, we found no previous report of vasovagal exercise
      induced syncope in a sedentary person. We present the case of a 35-year-old
      sedentary woman who experienced vasovagal syncope as she underwent an exercise
      stress test. Results of evaluations, including resting and stress
      electrocardiography and echocardiography, were normal. Her presentation is highly
      unusual: syncope has typically not been associated with exercise except in young
      athletes, people with structural heart abnormalities, or people with a prolonged
      QT syndrome. To our knowledge, this is the first report of vasovagal syncope
      associated with exercise in a sedentary patient who had normal cardiac and
      electrophysiologic function. We suggest possible physiologic mechanisms and
      diagnostic strategies. 

PMID- 25593530
TI  - Ruptured mycotic common femoral artery pseudoaneurysm: fatal pulmonary embolism
      after emergency stent-grafting in a drug abuser.
AB  - The rupture of a mycotic femoral artery pseudoaneurysm in an intravenous drug
      abuser is a limb- and life-threatening condition that necessitates emergency
      intervention. Emergency stent-grafting appears to be a viable, minimally invasive
      alternative, or a bridge, to subsequent open surgery. Caution is required in
      cases of suspected concomitant deep vein thrombosis in order to minimize the
      possibility of massive pulmonary embolism during stent-grafting, perhaps by
      omitting stent-graft postdilation or by inserting an inferior vena cava filter
      first. We describe the emergency endovascular management, in a 60-year-old male
      intravenous drug abuser, of a ruptured mycotic femoral artery pseudoaneurysm,
      which was complicated by a fatal pulmonary embolism. 

PMID- 25593531
TI  - Necrotic bowel induces takotsubo-like myocardial injury.
AB  - Although chest pain in association with ST-segment electrocardiographic deviation
      is often indicative of cardiac ischemia, it has also been associated with
      noncardiac conditions. The case of a 63-year-old woman that we report here is
      extraordinary because her presentation of "acute abdomen" did not appear severe
      enough to warrant urgent surgical intervention, whereas the chest pain and
      electrocardiographic changes (supported by rising troponin levels) created strong
      clinical suspicion of acute coronary syndrome. Was the evidence of cardiac
      ischemia a primary event, or was it a sequela of an acute surgical condition?
      Noncardiac surgical cases associated with evidence of myocardial injury can be
      extremely challenging from a diagnostic and management perspective. We believe
      that the accuracy of the clinical diagnosis is crucial to a well-considered
      approach. 

PMID- 25593532
TI  - Percutaneous management of RetroFlex 3 balloon rupture and separation of the
      Edwards Sapien delivery system.
AB  - We report the case of an 85-year-old woman with severe aortic stenosis who
      underwent transcatheter aortic valve replacement with use of the Edwards
      Sapien((r)) valve system. The procedure was complicated by rupture of the valve
      deployment balloon, with separation and retention of the nose cone of the
      RetroFlex 3((r)) delivery system in the iliac artery. Our endovascular retrieval
      of the equipment was successful, and we achieved access-site hemostasis by
      deploying a covered stent. To our knowledge, this is the first report of the
      endovascular retrieval of a malfunctioning delivery system during transcatheter
      aortic valve replacement. 

PMID- 25593533
TI  - Anticoagulation with bivalirudin during deep hypothermic circulatory arrest in a
      patient with heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia is a well-recognized complication of
      anticoagulation with heparin. We present the case of a patient with recent
      heparin-induced thrombocytopenia who subsequently needed surgery on an emergency
      basis for acute type A aortic dissection. This article reports the successful use
      of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin
      throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We
      contend that bivalirudin is a safe alternative to heparin when performing surgery
      for aortic dissection and should be considered as an option for use in patients
      who present with heparin-induced thrombocytopenia. 

PMID- 25593534
TI  - Concurrent aortic valvular disease and pulmonary sequestration: clinical
      implications.
AB  - Pulmonary sequestration refers to segmental lung tissue that has no connection
      with the bronchial tree or pulmonary arteries. In adults, the clinical sequelae
      are usually related to infection. Patients are typically referred for
      sequestrectomy even when they are asymptomatic. There are no guidelines for
      treating patients who have pulmonary sequestration and coexisting cardiac
      valvular disease, in which case the venous drainage patterns of sequestra pose
      the additional risks of infective endocarditis and volume overload. We present
      the cases of 2 adult patients--one symptomatic and one asymptomatic--who had
      concurrent aortic valvular disease and pulmonary sequestration, and we discuss
      the factors involved in our evaluation of their cardiac risk and our treatment
      decisions. In view of the sparse data to predict cardiac risks, we think that
      pulmonary sequestrectomy in adult patients with concurrent valvular conditions
      should be considered on a case-by-case basis.

PMID- 25593535
TI  - Internal mammary artery graft dissection: a case-based retrospective study and
      brief review.
AB  - The left internal mammary artery is the preferred graft for treating left
      anterior descending coronary artery disease. Dissection is a rare but grave
      sequela of internal mammary artery graft angiography. The available medical
      literature is scant, perhaps as a result of under-reporting. We report a case in
      which dissection of the internal mammary artery graft occurred during diagnostic
      angiography, and we discuss its management. In addition, we review the available
      literature and provide a retrospective analysis of the data from our own
      catheterization laboratory. In our single-center analysis of 542 cases of
      selective internal mammary artery graft angiography, we found only the single
      case of internal mammary artery graft dissection (0.2%) that we report here. Our
      review of the literature revealed 7 reported cases of internal mammary artery
      graft dissection, 3 of which were iatrogenic. There were no identifiable risk
      factors for such dissection. After treatment with angioplasty and stenting, all
      patients had good outcomes during follow-up. 

PMID- 25593536
TI  - Benefits and limitations of multimodality imaging in the diagnosis of a primary
      cardiac lymphoma.
AB  - Primary cardiac tumors are far rarer than tumors metastatic to the heart.
      Angiosarcoma is the primary cardiac neoplasm most frequently detected; lymphomas
      constitute only 1% of primary cardiac tumors. We present the case of a 55-year
      old woman with a recently diagnosed intracardiac mass who was referred to our
      institution for consideration of urgent orthotopic heart transplantation. Initial
      images suggested an angiosarcoma; however, a biopsy specimen of the mass was
      diagnostic for diffuse large B-cell lymphoma. The patient underwent chemotherapy
      rather than surgery, and she was asymptomatic 34 months later. We use our
      patient's case to discuss the benefits and limitations of multiple imaging
      methods in the evaluation of cardiac masses. Certain features revealed by
      computed tomography, cardiac magnetic resonance, and positron emission tomography
      can suggest a diagnosis of angiosarcoma rather than lymphoma. Cardiac magnetic
      resonance and positron emission tomography enable reliable distinction between
      benign and malignant tumors; however, the characteristics of different malignant
      tumors can overlap. Despite the great usefulness of multiple imaging methods for
      timely diagnosis, defining the extent of spread and the hemodynamic impact, and
      monitoring responses to treatment, we think that biopsy analysis is still
      warranted in order to obtain a correct histologic diagnosis in cases of suspected
      malignant cardiac tumors. 

PMID- 25593537
TI  - Pheochromocytoma-induced atrial tachycardia leading to cardiogenic shock and
      cardiac arrest: resolution with atrioventricular node ablation and pacemaker
      placement.
AB  - Pheochromocytoma should be considered in young patients who have acute cardiac
      decompensation, even if they have no history of hypertension. Atrioventricular
      node ablation and pacemaker placement should be considered for stabilizing
      pheochromocytoma patients with cardiogenic shock due to atrial tachyarrhythmias.
      A 38-year-old black woman presented with cardiogenic shock (left ventricular
      ejection fraction, <0.15) that did not respond to the placement of an intra
      aortic balloon pump. A TandemHeart((r)) Percutaneous Ventricular Assist Device
      was inserted emergently. After atrioventricular node ablation and placement of a
      temporary pacemaker, the TandemHeart was removed. Computed tomography of the
      abdomen revealed a pheochromocytoma. After placement of a permanent pacemaker,
      the patient underwent a right adrenalectomy. This is, to our knowledge, the first
      reported case of pheochromocytoma-induced atrial tachyarrhythmia that led to
      cardiogenic shock and cardiac arrest unresolved by the placement of 2 different
      ventricular assist devices, but that was completely reversed by radiofrequency
      ablation of the atrioventricular node and the placement of a temporary pacemaker.
      We present the patient's clinical, laboratory, and imaging findings, and we
      review the relevant literature. 

PMID- 25593538
TI  - Importance of absent ductus arteriosus in tetralogy of Fallot with absent
      pulmonary valve syndrome.
AB  - Tetralogy of Fallot without pulmonary valve syndrome is almost always associated
      with an absent ductus arteriosus. Patients with right aortic arch and
      retroesophageal left subclavian artery have a vascular ring if the left ductus
      arteriosus or its remnant and the Kommerell diverticulum are present. We report
      the cases of 2 infants in whom the role of an absent ductus arteriosus or its
      remnant is noteworthy. Both patients had a combination of tetralogy of Fallot
      with absent pulmonary valve syndrome and right aortic arch with retroesophageal
      left subclavian artery without a vascular ring. The absence of the ductus
      arteriosus has a role in the pathogenesis of tetralogy of Fallot with absent
      pulmonary valve syndrome. The absence of a ductus arteriosus in the right aortic
      arch with retroesophageal left subclavian artery precludes a vascular ring. 

PMID- 25593539
TI  - Aortic valve endocarditis complicated by ST-elevation myocardial infarction.
AB  - Infective endocarditis complicated by abscess formation and coronary artery
      compression is a rare clinical event with a high mortality rate, and diagnosis
      requires a heightened degree of suspicion. We present the clinical, angiographic,
      and echocardiographic features of a 73-year-old woman who presented with dyspnea
      and was found to have right coronary artery compression that was secondary to
      abscess formation resulting from diffuse infectious endocarditis. We discuss the
      patient's case and briefly review the relevant medical literature. To our
      knowledge, this is the first reported case of abscess formation involving a
      native aortic valve and the right coronary artery. 

PMID- 25593540
TI  - Renal cell carcinoma extending into the retrohepatic inferior vena cava.

PMID- 25593541
TI  - Ectopic right renal artery originating from anomalous common celio-mesenteric
      trunk: multifaceted imaging approach.

PMID- 25593542
TI  - Coronary artery aneurysms in a 15-year-old boy.

PMID- 25593543
TI  - Keeping cool in the operating room.

PMID- 25593544
TI  - Consider a mitochondrial disorder when left ventricular
      hypertrabeculation/noncompaction is associated with renal cysts.

PMID- 25593545
TI  - One Polymorph and Various Morphologies of Phenytoin at a Silica Surface Due to
      Preparation Kinetics.
AB  - The preparation of solid crystalline films at surfaces is of great interest in a
      variety of fields. Within this work the preparation of pharmaceutically relevant
      thin films containing the active pharmaceutical ingredient phenytoin is
      demonstrated. The preparation techniques applied include drop casting, spin
      coating, and vacuum deposition. For the solution processed samples a decisive
      impact of the solution concentration and the applied film fabrication technique
      is observed; particular films form for all samples but with their extensions
      along different crystallographic directions strongly altered. Vacuum deposition
      of phenytoin reveals amorphous films, which over time crystallize into needle
      like or particular-type structures whereby a nominal thickness of 50 nm is
      required to achieve a fully closed layer. Independent of all preparation
      techniques, the resulting polymorph is the same for each sample as confirmed by
      specular X-ray diffraction scans. Thus, morphologies observed via optical and
      atomic force microscope techniques are therefore a result of the preparation
      technique. This shows that the different time scales for which crystallization is
      obtained is the driving force for the various morphologies in phenytoin thin
      films rather than the presence of another polymorph forming.

PMID- 25593547
TI  - Fabrication, electrical characterization, and detection application of graphene
      sheet-based electrical circuits.
AB  - The distribution of potential, electric field, and gradient of square of electric
      field was simulated via a finite element method for dielectrophoresis (DEP)
      assembly. Then reduced graphene oxide sheets (RGOS)- and graphene oxide sheets
      (GOS)-based electrical circuits were fabricated via DEP assembly. The
      mechanically exfoliated graphene sheets (MEGS)-based electrical circuit was also
      fabricated for comparison. The electrical transport properties of three types of
      graphene-based electrical circuits were measured. The MEGS-based electrical
      circuit possesses the best electrical conductivity, and the GOS-based electrical
      circuit has the poorest electrical conductivity among all three circuits. The
      three types of electrical circuits were applied for the detection of copper ions
      (Cu(2+)). The RGOS-based electrical circuit can detect the Cu(2+) when the
      concentration of Cu(2+) was as low as 10 nM in solution. The GOS-based electrical
      circuit can only detect Cu(2+) after chemical reduction. The possible mechanism
      of electron transfer was proposed for the detection. The facile fabrication
      method and excellent performance imply the RGOS-based electrical circuit has
      great potential to be applied to metal ion sensors. 

PMID- 25593546
TI  - Point-of-Care HbA1c Testing with the A1cNow Test Kit in General Practice Dental
      Clinics: A Pilot Study Involving Its Accuracy and Practical Issues in Its Use.
AB  - With millions of at-risk people undiagnosed with pre-diabetes and diabetes, there
      is a need to identify alternate screening sites for out-of-range glucose values.
      We examined practical issues and accuracy (relative to High Performance Liquid
      Chromatography testing in a laboratory) in the use of the A1cNow point of care
      device for this screening in general practice dental clinics at a large
      University-based Dental College. Health care professionals obtained evaluable
      readings for only 70% of the subjects, even after two attempts, and its use
      according to manufacturer's instructions was often challenging in the busy
      environment of the dental clinic. At thresholds for pre-diabetes and diabetes
      established by the American Diabetes Association, sensitivities of the A1cNow kit
      relative to the HPLC method were 91.9% and 100%, respectively. However,
      specificities for pre-diabetes and diabetes were 66.7% and 82.4%, respectively,
      indicating many false positive results. A better strategy for diabetes screening
      may involve a laboratory-based analysis approach that is patient- and provider
      friendly, with minimal burden to the dental team.

PMID- 25593548
TI  - Dislocation luminescence in GaN single crystals under nanoindentation.
AB  - This work presents an experimental study on the dislocation luminescence in GaN
      by nanoindentation, cathodoluminescence, and Raman. The dislocation luminescence
      peaking at 3.12 eV exhibits a series of special properties in the
      cathodoluminescence measurements, and it completely disappears after annealing at
      500 degrees C. Raman spectroscopy shows evidence for existence of vacancies in
      the indented region. A comprehensive investigation encompassing
      cathodoluminescence, Raman, and annealing experiments allow the assignment of
      dislocation luminescence to conduction-band-acceptor transition involving Ga
      vacancies. The nanoscale plasticity of GaN can be better understood by
      considering the dislocation luminescence mechanism. 

PMID- 25593550
TI  - Performance enhancement of ITO/oxide/semiconductor MOS-structure silicon solar
      cells with voltage biasing.
AB  - In this study, we demonstrate the photovoltaic performance enhancement of a p-n
      junction silicon solar cell using a transparent-antireflective ITO/oxide film
      deposited on the spacing of the front-side finger electrodes and with a DC
      voltage applied on the ITO-electrode. The depletion width of the p-n junction
      under the ITO-electrode was induced and extended while the absorbed volume and
      built-in electric field were also increased when the biasing voltage was
      increased. The photocurrent and conversion efficiency were increased because more
      photo-carriers are generated in a larger absorbed volume and because the carriers
      transported and collected more effectively due to higher biasing voltage effects.
      Compared to a reference solar cell (which was biased at 0 V), a conversion
      efficiency enhancement of 26.57% (from 12.42% to 15.72%) and short-circuit
      current density enhancement of 42.43% (from 29.51 to 42.03 mA/cm(2)) were
      obtained as the proposed MOS-structure solar cell biased at 2.5 V. In addition,
      the capacitance-volt (C-V) measurement was also used to examine the mechanism of
      photovoltaic performance enhancement due to the depletion width being enlarged by
      applying a DC voltage on an ITO-electrode. 

PMID- 25593549
TI  - Chemical and magnetic functionalization of graphene oxide as a route to enhance
      its biocompatibility.
AB  - The novel approach for deposition of iron oxide nanoparticles with narrow size
      distribution supported on different sized graphene oxide was reported. Two
      different samples with different size distributions of graphene oxide (0.5 to 7
      MUm and 1 to 3 MUm) were selectively prepared, and the influence of the flake
      size distribution on the mitochondrial activity of L929 with WST1 assay in vitro
      study was also evaluated. Little reduction of mitochondrial activity of the GO
      Fe3O4 samples with broader size distribution (0.5 to 7 MUm) was observed. The
      pristine GO samples (0.5 to 7 MUm) in the highest concentrations reduced the
      mitochondrial activity significantly. For GO-Fe3O4 samples with narrower size
      distribution, the best biocompatibility was noticed at concentration 12.5 MUg/mL.
      The highest reduction of cell viability was noted at a dose 100 MUg/mL for GO (1
      to 3 MUm). It is worth noting that the chemical functionalization of GO and Fe3O4
      is a way to enhance the biocompatibility and makes the system independent of the
      size distribution of graphene oxide. 

PMID- 25593551
TI  - Effects of photo-assisted electrodeposited on CuInSe2 thin films.
AB  - Photo-assisted one-step electrodeposition has been applied to help in forming
      smooth and dense CuInSe2 films. The difference in surface morphology and
      crystalline quality between CuInSe2 films with various photo-assistance has been
      investigated. In the photo-assisted electrodeposition process, the many kinds of
      lamps providing maximum light intensity at about 380 to 620 nm were used as light
      source to be irradiated onto the surface of Mo-coated soda-lime glass substrates.
      The results suggested effects of photo-assistance including activating surface
      diffusion and growing high-crystalline quality films with reduced defects during
      electrodeposition. 

PMID- 25593552
TI  - Fabrication and investigation of the optoelectrical properties of MoS2/CdS
      heterojunction solar cells.
AB  - Molybdenum disulfide (MoS2)/cadmium sulfide (CdS) heterojunction solar cells were
      successfully synthesized via chemical bath deposition (CBD) and chemical vapor
      deposition (CVD). The as-grown CdS film on a fluorine tin oxide (FTO) substrate
      deposited by CBD is continuous and compact. The MoS2 film deposited by CVD is
      homogeneous and continuous, with a uniform color and a thickness of approximately
      10 nm. The optical absorption range of the MoS2/CdS heterojunction covers the
      visible and near-infrared spectral regions of 350 to 800 nm, which is beneficial
      for the improvement of solar cell efficiency. Moreover, the MoS2/CdS solar cell
      exhibits good current-voltage (I-V) characteristics and pronounced photovoltaic
      behavior, with an open-circuit voltage of 0.66 V and a short-circuit current
      density of 0.227 * 10(-6) A/cm(2), comparable to the results obtained from other
      MoS2-based solar cells. This research is critical to investigate more efficient
      and stable solar cells based on graphene-like materials in the future. 

PMID- 25593553
TI  - Utilization of triangle nanosilver to prepare spherical nanosilver and
      quantitatively detect trace titanium by SERS.
AB  - The blue triangle nanosilver (BAgNP) sol was prepared by the two reducers of
      NaBH4 and H2O2. Using BAgNP as the precursor, a small spherical nanosilver (AgNP)
      sol in yellow was synthesized by addition of suitable amounts of X (-) (X = Cl,
      Br, and I). The oxidization process of BAgNP to AgNP was studied in detail by
      resonance Rayleigh scattering (RRS), surface-enhanced Raman scattering (SERS),
      laser scattering, surface plasmon resonance (SPR) absorption, and microscope
      techniques. It has been observed that NaCl accelerated the oxidizing BAgNP to
      form AgNP, and an oxidizing mechanism and quasi-nanograting Raman-scattering
      enhanced mechanism were developed to explain the phenomena. Using the BAgNP sol
      as substrate and based on the catalysis of Ti(IV) on the BrO3 (-) oxidizing
      safranine T (ST) molecular probe with a strong SERS peak at 1,535 cm(-1), a new
      catalytic SERS quantitative method was developed for the determination of 1.0 to
      100 ng/mL Ti, with a detection limit of 0.4 ng/mL. 

PMID- 25593554
TI  - Facile and high-efficient immobilization of histidine-tagged multimeric protein G
      on magnetic nanoparticles.
AB  - This work reports the high-efficient and one-step immobilization of multimeric
      protein G on magnetic nanoparticles. The histidine-tagged (His-tag) recombinant
      multimeric protein G was overexpressed in Escherichia coli BL21 by the repeated
      linking of protein G monomers with a flexible linker. High-efficient
      immobilization on magnetic nanoparticles was demonstrated by two different
      preparation methods through the amino-silane and chloro-silane functionalization
      on silica-coated magnetic nanoparticles. Three kinds of multimeric protein G such
      as His-tag monomer, dimer, and trimer were tested for immobilization efficiency.
      For these tests, bicinchoninic acid (BCA) assay was employed to determine the
      amount of immobilized His-tag multimeric protein G. The result showed that the
      immobilization efficiency of the His-tag multimeric protein G of the monomer,
      dimer, and trimer was increased with the use of chloro-silane-functionalized
      magnetic nanoparticles in the range of 98% to 99%, rather than the use of amino
      silane-functionalized magnetic nanoparticles in the range of 55% to 77%,
      respectively. 

PMID- 25593555
TI  - Real-time deflection and friction force imaging by bimorph-based resonance-type
      high-speed scanning force microscopy in the contact mode.
AB  - We report herein an alternative high-speed scanning force microscopy method in
      the contact mode based on a resonance-type piezoelectric bimorph scanner. The
      experimental setup, the modified optical beam deflection scheme suitable for
      smaller cantilevers, and a high-speed control program for simultaneous data
      capture are described in detail. The feature of the method is that the deflection
      and friction force images of the sample surface can be obtained simultaneously in
      real time. Images of various samples (e.g., a test grating, a thin gold film, and
      fluorine-doped tin oxide-coated glass slides) are acquired successfully. The
      imaging rate is 25 frames per second, and the average scan speed reaches a value
      of approximately 2.5 cm/s. The method combines the advantages of both observing
      the dynamic processes of the sample surface and monitoring the frictional
      properties on the nanometer scale. PACS: 07.79.Lh; 07.79.Sp; 68.37.Ps.

PMID- 25593556
TI  - Angle-dependent photodegradation over ZnO nanowire arrays on flexible paper
      substrates.
AB  - In this study, we grew zinc oxide (ZnO) nanowire arrays on paper substrates using
      a two-step growth strategy. In the first step, we formed single-crystalline ZnO
      nanoparticles of uniform size distribution (ca. 4 nm) as seeds for the
      hydrothermal growth of the ZnO nanowire arrays. After spin-coating of these seeds
      onto paper, we grew ZnO nanowire arrays conformally on these substrates. The
      crystal structure of a ZnO nanowire revealed that the nanowires were single
      crystalline and had grown along the c axis. Further visualization through annular
      bright field scanning transmission electron microscopy revealed that the
      hydrothermally grown ZnO nanowires possessed Zn polarity. From photocatalytic
      activity measurements of the ZnO nanowire (NW) arrays on paper substrate, we
      extracted rate constants of 0.415, 0.244, 0.195, and 0.08 s(-1) for the
      degradation of methylene blue at incident angles of 0 degrees , 30 degrees , 60
      degrees , and 75 degrees , respectively; that is, the photocatalytic activity of
      these ZnO nanowire arrays was related to the cosine of the incident angle of the
      UV light. Accordingly, these materials have promising applications in the design
      of sterilization systems and light-harvesting devices. 

PMID- 25593557
TI  - The effect of dye-sensitized solar cell based on the composite layer by anodic
      TiO2 nanotubes.
AB  - TiO2 nanotube arrays are very attractive for dye-sensitized solar cells (DSSCs)
      owing to their superior charge percolation and slower charge recombination.
      Highly ordered, vertically aligned TiO2 nanotube arrays have been fabricated by a
      three-step anodization process. Although the use of a one-dimensional structure
      provides an enhanced photoelectrical performance, the smaller surface area
      reduces the adsorption of dye on the TiO2 surface. To overcome this problem, we
      investigated the effect of DSSCs constructed with a multilayer photoelectrode
      made of TiO2 nanoparticles and TiO2 nanotube arrays. We fabricated the novel
      multilayer photoelectrode via a layer-by-layer assembly process and thoroughly
      investigated the effect of various structures on the sample efficiency. The DSSC
      with a four-layer photoelectrode exhibited a maximum conversion efficiency of
      7.22% because of effective electron transport and enhanced adsorption of dye on
      the TiO2 surface. 

PMID- 25593558
TI  - Doping concentration dependence of microstructure and magnetic behaviours in Co
      doped TiO2 nanorods.
AB  - Co-doped titanium dioxide (TiO2) nanorods with different doping concentrations
      were fabricated by a molten salt method. It is found that the morphology of TiO2
      changes from nanorods to nanoparticles with increasing doping concentration. The
      mechanism for the structure and phase evolution is investigated in detail.
      Undoped TiO2 nanorods show strong ferromagnetism at room temperature, whereas
      incorporating of Co deteriorates the ferromagnetic ordering. X-ray photoelectron
      spectroscopy (XPS) and electron spin resonance (ESR) results demonstrate that the
      ferromagnetism is associated with Ti vacancy. 

PMID- 25593559
TI  - CZTSe solar cells prepared by electrodeposition of Cu/Sn/Zn stack layer followed
      by selenization at low Se pressure.
AB  - Cu2ZnSnSe4 (CZTSe) thin films are prepared by the electrodeposition of stack
      copper/tin/zinc (Cu/Sn/Zn) precursors, followed by selenization with a tin source
      at a substrate temperature of 530 degrees C. Three selenization processes were
      performed herein to study the effects of the source of tin on the quality of
      CZTSe thin films that are formed at low Se pressure. Much elemental Sn is lost
      from CZTSe thin films during selenization without a source of tin. The loss of Sn
      from CZTSe thin films in selenization was suppressed herein using a tin source at
      400 degrees C (A2) or 530 degrees C (A3). A copper-poor and zinc-rich CZTSe
      absorber layer with Cu/Sn, Zn/Sn, Cu/(Zn + Sn), and Zn/(Cu + Zn + Sn) with
      metallic element ratios of 1.86, 1.24, 0.83, and 0.3, respectively, was obtained
      in a selenization with a tin source at 530 degrees C. The crystallized CZTSe thin
      film exhibited an increasingly (112)-preferred orientation at higher tin selenide
      (SnSe x ) partial pressure. The lack of any obvious Mo-Se phase-related
      diffraction peaks in the X-ray diffraction (XRD) diffraction patterns may have
      arisen from the low Se pressure in the selenization processes. The scanning
      electron microscope (SEM) images reveal a compact surface morphology and a
      moderate grain size. CZTSe solar cells with an efficiency of 4.81% were produced
      by the low-cost fabrication process that is elucidated herein. 

PMID- 25593560
TI  - Characterization and density control of GaN nanodots on Si (111) by droplet
      epitaxy using plasma-assisted molecular beam epitaxy.
AB  - In this report, self-organized GaN nanodots have been grown on Si (111) by
      droplet epitaxy method, and their density can be controlled from 1.1 * 10(10) to
      1.1 * 10(11) cm(-2) by various growth parameters, such as substrate temperatures
      for Ga droplet formation, the pre-nitridation treatment of Si substrate, the
      nitridation duration for GaN crystallization, and in situ annealing after GaN
      formation. Based on the characterization of in situ RHEED, we can observe the
      surface condition of Si and the formation of GaN nanodots on Si. The surface
      nitridaiton treatment at 600 degrees C provides a-SiNx layer which makes higher
      density of GaN nanodots. Crystal GaN nanodots can be observed by the HRTEM. The
      surface composition of GaN nanodots can be analyzed by SPEM and MU-XPS with a
      synchrotron x-ray source. We can find GaN nanodots form by droplet epitaxy and
      then in situ annealing make higher-degree nitridation of GaN nanodots. 

PMID- 25593561
TI  - Retardation of nanoparticles growth by doping.
AB  - The process of doping of CdS nanoparticles with Mn during colloidal synthesis is
      analyzed by EPR and optical studies. Analysis of EPR results demonstrated that
      Mn(2+) ions are successfully incorporated into the nanoparticles and occupy the
      crystal sites both in the bulk of a NP and near the surface of a NP. Optical
      absorption measurements revealed the retardation of absorption edge shift during
      the growth for Mn-doped CdS NPs as compared to the undoped CdS NPs. It was
      concluded that the presence of Mn in the solution leads to the inhibition of NPs
      growth. 

PMID- 25593562
TI  - Synthesis of gallium nitride nanostructures by nitridation of electrochemically
      deposited gallium oxide on silicon substrate.
AB  - Gallium nitride (GaN) nanostructures were successfully synthesized by the
      nitridation of the electrochemically deposited gallium oxide (Ga2O3) through the
      utilization of a so-called ammoniating process. Ga2O3 nanostructures were firstly
      deposited on Si substrate by a simple two-terminal electrochemical technique at a
      constant current density of 0.15 A/cm(2) using a mixture of Ga2O3, HCl, NH4OH and
      H2O for 2 h. Then, the deposited Ga2O3 sample was ammoniated in a horizontal
      quartz tube single zone furnace at various ammoniating times and temperatures.
      The complete nitridation of Ga2O3 nanostructures at temperatures of 850 degrees C
      and below was not observed even the ammoniating time was kept up to 45 min. After
      the ammoniating process at temperature of 900 degrees C for 15 min, several
      prominent diffraction peaks correspond to hexagonal GaN (h-GaN) planes were
      detected, while no diffraction peak of Ga2O3 structure was detected, suggesting a
      complete transformation of Ga2O3 to GaN. Thus, temperature seems to be a key
      parameter in a nitridation process where the deoxidization rate of Ga2O3 to
      generate gaseous Ga2O increase with temperature. The growth mechanism for the
      transformation of Ga2O3 to GaN was proposed and discussed. It was found that a
      complete transformation can not be realized without a complete deoxidization of
      Ga2O3. A significant change of morphological structures takes place after a
      complete transformation of Ga2O3 to GaN where the original nanorod structures of
      Ga2O3 diminish, and a new nanowire-like GaN structures appear. These results show
      that the presented method seems to be promising in producing high-quality h-GaN
      nanostructures on Si. 

PMID- 25593564
TI  - IF YOU BUILD IT WILL THEY COME? TEACHERS' ONLINE USE OF STUDENT PERFORMANCE DATA.
AB  - Testing of students and computer systems to store, manage, analyze, and report
      the resulting test data have grown hand-in-hand. Extant research on teacher use
      of electronically stored data are largely qualitative and focused on the
      conditions necessary (but not sufficient) for effective teacher data use. Absent
      from the research is objective information on how much and in what ways teachers
      use computer-based student test data, even when supposed precursors of usage are
      in place. This paper addresses this knowledge gap by analyzing the online
      activities of teachers in one mid-size urban district. Utilizing Web logs
      collected between 2008 and 2010, I find low teacher interaction with Web-based
      pages that contain student test information that could potentially inform
      practice. I also find no evidence that teacher usage of Web-based student data
      are related to student achievement gains, but there is reason to believe these
      estimates are downwardly biased.

PMID- 25593563
TI  - Shoulder impairment before breast cancer surgery.
AB  - OBJECTIVE: To compare pre- and post-operative shoulder active range of motion
      (AROM) values from female breast cancer survivors to population norm values for
      shoulder AROM; and to compare shoulder AROM differences pre- and post-surgery
      between female African American and White breast cancer survivors (BCA). STUDY
      DESIGN: This pilot study used a convenience sample and longitudinal design
      measuring participants 2 times (T0 = baseline, after biopsy but within 2 weeks
      before BCA surgery; T1 = 2nd postoperative week). BACKGROUND: The U.S. has the
      largest BCA survivor population in history and yet the mortality burden remains
      highest among AA BCA survivors. AAs may also have greater burden of physical and
      functional side effects compared to whites and the general population. METHODS
      AND MEASURES: The data were collected from a convenience sample (n = 33; nAA = 9,
      nW = 24) and included data on shoulder AROM, medical chart review for pre- and co
      morbid conditions, and self-reported demographics and medical history. We used t
      tests to compare sample AROM means to population norms. We then compared our
      sample across 2 timepoints (T0 = pre-surgery; T1 = 2 weeks post-surgery) using
      independent samples t-tests and repeated measures analysis of variance (p < .05)
      to compare AA to White sub-samples AROM means. RESULTS: African Americans had
      significantly less shoulder abduction (at T0) and flexion (at T1) than whites.
      However, 100% had significantly reduced AROM for all movements at T0 (prior to
      surgery but after biopsy) when compared to population norms. CONCLUSIONS: The
      significant reduction in shoulder AROM after biopsy but before surgery points to
      a possible unmet need for early physical therapy intervention. Further research
      using randomized controlled trial design is recommended.

PMID- 25593565
TI  - Quantifying CD4 receptor protein in two human CD4+ lymphocyte preparations for
      quantitative flow cytometry.
AB  - BACKGROUND: In our previous study that characterized different human CD4+
      lymphocyte preparations, it was found that both commercially available
      cryopreserved peripheral blood mononuclear cells (PBMC) and a commercially
      available lyophilized PBMC (Cyto-TrolTM) preparation fulfilled a set of criteria
      for serving as biological calibrators for quantitative flow cytometry. However,
      the biomarker CD4 protein expression level measured for T helper cells from Cyto
      Trol was about 16% lower than those for cryopreserved PBMC and fresh whole blood
      using flow cytometry and mass cytometry. A primary reason was hypothesized to be
      due to steric interference in anti- CD4 antibody binding to the smaller sized
      lyophilized control cells. METHOD: Targeted multiple reaction monitoring (MRM)
      mass spectrometry (MS) is used to quantify the copy number of CD4 receptor
      protein per CD4+ lymphocyte. Scanning electron microscopy (SEM) is utilized to
      assist searching the underlying reasons for the observed difference in CD4
      receptor copy number per cell determined by MRM MS and CD4 expression measured
      previously by flow cytometry. RESULTS: The copy number of CD4 receptor proteins
      on the surface of the CD4+ lymphocyte in cryopreserved PBMCs and in lyophilized
      control cells is determined to be (1.45 +/- 0.09) * 10(5) and (0.85 +/- 0.11) *
      10(5), respectively, averaged over four signature peptides using MRM MS. In
      comparison with cryopreserved PBMCs, there are more variations in the CD4 copy
      number in lyophilized control cells determined based on each signature peptide.
      SEM images of CD4+ lymphocytes from lyophilized control cells are very different
      when compared to the CD4+ T cells from whole blood and cryopreserved PBMC.
      CONCLUSION: Because of the lyophilization process applied to Cyto-Trol control
      cells, a lower CD4 density value, defined as the copy number of CD4 receptors per
      CD4+ lymphocyte, averaged over three different production lots is most likely
      explained by the loss of the CD4 receptors on damaged and/or broken microvilli
      where CD4 receptors reside. Steric hindrance of antibody binding and the
      association of CD4 receptors with other biomolecules likely contribute
      significantly to the nearly 50% lower CD4 receptor density value for
      cryopreserved PBMC determined from flow cytometry compared to the value obtained
      from MRM MS.

PMID- 25593567
TI  - Perspectives in Health Information Management. Fall 2014 introduction.

PMID- 25593566
TI  - LecT-Hepa facilitates estimating treatment outcome during interferon therapy in
      chronic hepatitis C patients.
AB  - BACKGROUND: A combination treatment of interferon and ribavirin is the standard
      and the commonly used treatment for chronic hepatitis C (CHC). Developing
      noninvasive tests like serum indicators that can predict treatment outcome at an
      early stage of therapy is beneficial for individualized treatment and management
      of CHC. A glyco-indicator based on the glyco-alteration of serum alpha1-acid
      glycoprotein, LecT-Hepa, was discovered by glycomics technologies as a robust
      indicator of liver fibrosis. Here, we investigated the clinical utility of LecT
      Hepa for evaluation of treatment outcome. RESULTS: Firstly, ninety-seven patients
      with CHC were used for comparison of LecT-Hepa in serum and plasma. We found no
      significant difference in the concentrations of LecT-Hepa in serum and plasma.
      And then, 213 serum specimens from 45 patients who received 48 weeks of treatment
      with interferon and ribavirin were followed up for 96 weeks, and were used for
      evaluation of the role of LecT-Hepa. We found that LecT-Hepa might reflect the
      change in fibrosis regression during the treatment process. Moreover, the change
      of LecT-Hepa at the first 12 weeks of treatment could already predict the
      antiviral treatment response, which was more superior to FIB-4 index and
      aspartate aminotransferase-to-platelet ratio index (APRI) in this study.
      CONCLUSIONS: These results provide a new perspective that serum glycoprotein
      could be used as a joint diagnosis indicator for estimation treatment outcome of
      viral hepatitis at earlier stage of therapy.

PMID- 25593568
TI  - Can utilizing a computerized provider order entry (CPOE) system prevent hospital
      medical errors and adverse drug events?
AB  - Computerized provider order entry (CPOE) systems allow physicians to prescribe
      patient services electronically. In hospitals, CPOE essentially eliminates the
      need for handwritten paper orders and achieves cost savings through increased
      efficiency. The purpose of this research study was to examine the benefits of and
      barriers to CPOE adoption in hospitals to determine the effects on medical errors
      and adverse drug events (ADEs) and examine cost and savings associated with the
      implementation of this newly mandated technology. This study followed a
      methodology using the basic principles of a systematic review and referenced 50
      sources. CPOE systems in hospitals were found to be capable of reducing medical
      errors and ADEs, especially when CPOE systems are bundled with clinical decision
      support systems designed to alert physicians and other healthcare providers of
      pending lab or medical errors. However, CPOE systems face major barriers
      associated with adoption in a hospital system, mainly high implementation costs
      and physicians' resistance to change. 

PMID- 25593569
TI  - Electronic health records: what are the most important barriers?
AB  - INTRODUCTION: The process of design and adoption of electronic health records may
      face a number of barriers. This study aimed to compare the importance of the main
      barriers from the experts' point of views in Iran. METHODS: This survey study was
      completed in 2011. The potential participants (62 experts) included faculty
      members who worked in departments of health information technology and
      individuals who worked in the Ministry of Health in Iran and were in charge of
      the development and adoption of electronic health records. No sampling method was
      used in this study. Data were collected using a Likert-scale questionnaire
      ranging from 1 to 5. The validity of the questionnaire was established using
      content and face validity methods, and the reliability was calculated using
      Cronbach's alpha coefficient. RESULTS: The response rate was 51.6 percent. The
      participants' perspectives showed that the most important barriers in the process
      of design and adoption of electronic health records were technical barriers (mean
      = 3.84). Financial and ethical-legal barriers, with the mean value of 3.80 were
      other important barriers, and individual and organizational barriers, with the
      mean values of 3.59 and 3.50 were found to be less important than other barriers
      from the experts' perspectives. CONCLUSION: Strategic planning for the creation
      and adoption of electronic health records in the country, creating a team of
      experts to assess the potential barriers and develop strategies to eliminate
      them, and allocating financial resources can help to overcome most important
      barriers to the adoption of electronic health records.

PMID- 25593570
TI  - Examination of office visit patient preferences for the after-visit summary
      (AVS).
AB  - The federal government advocates the practice of routinely providing an after
      visit summary (AVS) to patients after each office-based visit as an element of
      stage 1 meaningful use. A significant potential benefit of the AVS is improved
      patient engagement achieved by enabling patients and family members to better
      understand and retain key health information. The methodology for this study was
      a mixed-methods pilot study to examine, through the perspectives of adult primary
      care patients, how relevant and actionable data can be better formatted in the
      AVS. Results of this study suggest that the goal of the AVS to serve as a
      communication tool to engage and support patients is frequently not being met.
      Further study is needed to understand, from the viewpoints of patients and
      providers, what barriers are keeping them from optimally providing and using the
      information on the AVS. 

PMID- 25593571
TI  - Integrating research data capture into the electronic health record workflow:
      real-world experience to advance innovation.
AB  - As the adoption of electronic health records (EHRs) increases, more opportunities
      are available for leveraging the system and the data to facilitate research.
      Historically, for patients enrolled in clinical research trials or studies, data
      have been documented in the medical record, and then study-related data are
      manually reentered into an electronic case report form in a research system. By
      utilizing data collected in the EHR to prepopulate electronic case report forms,
      manual transcription is reduced, data quality is improved, and the workflow for
      capturing research data is streamlined. Past efforts to integrate EHRs and
      research systems for the purposes of data capture have demonstrated that
      interoperability is possible. This article highlights how Cerner Corporation and
      Florida Hospital collaborated to extend an existing standard to implement a
      workflow called Integrated Data Capture. 

PMID- 25593572
TI  - A journey through meaningful use at a large academic medical center: lessons of
      leadership, administration, and technical implementation.
AB  - Successfully reporting meaningful use of electronic health records to the Centers
      for Medicare and Medicaid Services can be a challenging process, particularly for
      healthcare organizations with large numbers of eligible professionals. This case
      report describes a successful meaningful use attestation process undertaken at a
      major academic medical center. It identifies best practices in the areas of
      leadership, administration, communication, ongoing support, and technological
      implementation. 

PMID- 25593573
TI  - Survey of state health information exchanges regarding inclusion of Continuity of
      Care Documents for long-term post-acute care (LTPAC) patient assessment.
AB  - OBJECTIVES: This study aimed to measure awareness and interest among state health
      information exchanges (HIEs) in a tool that translates long-term post-acute care
      (LTPAC) patient assessment information to a Continuity of Care Document (CCD)
      format for sharing; whether any state HIEs currently integrate patient
      information from LTPAC providers; and the anticipated benefits and barriers to
      using such a tool. MATERIALS AND METHODS: The study consisted of an online survey
      of state HIEs. RESULTS: Responses were received from representatives of 29 of the
      51 HIEs (57 percent). Eleven of the 29 respondents (38 percent) were aware of the
      LTPAC-to-CCD translation tool, and 24 (83 percent of respondents) were interested
      in it or felt LTPAC providers in their state would be interested. Twenty-one of
      the 24 interested respondents (88 percent) indicated a desire for more
      information about this technology. DISCUSSION: Skilled nursing facilities and
      home health agencies receive no incentives for adoption of electronic health
      record systems and are not commonly included in HIEs. These organizations do,
      however collect extensive structured data about their patients (Minimum Data Set
      for nursing facilities, Outcome and Assessment Information Set for home health
      agencies) and transmit the data electronically to the Centers for Medicare and
      Medicaid Services (CMS). A tool is now available that will intercept the
      transmissions to CMS, transform content extracted from patient assessments into
      CCDs, and send the CCDs to a designated HIE. CONCLUSION: Responding HIEs reported
      almost no experience exchanging patient assessment information from LTPAC
      providers. Anticipated benefits include safer care transitions; anticipated
      barriers include information technology constraints in LTPAC settings.

PMID- 25593574
TI  - What caused the breach? An examination of use of information technology and
      health data breaches.
AB  - Data breaches arising from theft, loss, unauthorized access/disclosure, improper
      disclosure, or hacking incidents involving personal health information continue
      to increase every year. As of September 2013, reported breaches affecting
      individuals reached close to 27 million since 2009, when compilation of records
      on breaches began. These breaches, which involved 674 covered entities and 153
      business associates, involved computer systems and networks, desktop computers,
      laptops, paper, e-mail, electronic health records, and removable/portable devices
      (CDs, USBs, x-ray films, backup tapes, etc.). Even with the increased use of
      health information technology by health institutions and allied businesses, theft
      and loss (not hacking) constitute the major types of data breaches encountered.
      Removable/portable devices, desktop computers, and laptops were the top sources
      or locations of the breached information, while the top six states-Virginia,
      Illinois, California, Florida, New York, and Tennessee-in terms of the number of
      reported breaches accounted for nearly 75 percent of the total individual
      breaches, 33 percent of breaches in covered entities, and about 30 percent of the
      total breaches involving business associates. 

PMID- 25593575
TI  - Cardiac rehabilitation and mid-term follow-up after transcatheter aortic valve
      implantation.
AB  - BACKGROUND: Evaluation of patient outcomes following transcatheter aortic valve
      implantation (TAVI) has usually been based on survival and clinical improvement.
      Studies on quality of life are limited, and data from comprehensive assessments
      after the procedure are lacking. METHODS: Sixty patients referred for cardiac
      rehabilitation after TAVI underwent in-hospital and after-discharge
      multidimensional assessments to evaluate clinical, functional, and nutritional
      statuses, degree of autonomy, cognitive impairment, depression and quality of
      life. RESULTS: On admission to rehabilitation, approximately half of the patients
      had severe functional impairment and dependence for basic activities of daily
      living. During their hospital stay, one-third of the patients suffered
      significant clinical complications and two had to be transferred to the
      implantation center. Despite this, the overall outcome was very good. All of the
      remaining patients were clinically stable at discharge and functional status,
      autonomy and quality of life were improved in most. During a mean follow-up of
      540 days (range: 192-738 days), five patients died from noncardiac causes, three
      were hospitalized for cardiac events, and nine for non cardiac reasons.
      Functional status and autonomy remained satisfactory in the majority of patients
      and most continued to live independently. CONCLUSIONS: Patients referred for
      rehabilitation after TAVI are often very frail, with a high grade of functional
      impairment, dependence on others and high risk of clinical complications. During
      a rehabilitation programme, based on a multidimensional assessment and
      intervention, most patients showed significant improvement in functional status,
      quality of life, and autonomy, which remained stable in the majority of subjects
      during mid-term follow-up.

PMID- 25593576
TI  - Effect of transcatheter aortic valve implantation on QT dispersion in patients
      with aortic stenosis.
AB  - BACKGROUND: QT dispersion (QTd) is a predictor of ventricular arrhythmia.
      Ventricular arrhythmia is an important factor influencing morbidity and mortality
      in patients with aortic stenosis. Surgical aortic valve replacement reduced the
      QTd in this patients group. However, the effect of transcatheter aortic valve
      implantation (TAVI) on QTd in patients with aortic stenosis is unknown. The aim
      of this study was to investigate the effect of TAVI on QTd in patients with
      aortic stenosis. METHODS: Patients with severe aortic stenosis, who were not
      candidates for surgical aortic valve replacement due to contraindications or high
      surgical risk, were included in the study. All patients underwent
      electrocardiographic and echocardiographic evaluation before, and at the 6(th)
      month after TAVI, computed QTd and left ventricular mass index (LVMI). RESULTS: A
      total 30 patients were admitted to the study (mean age 83.2 +/- 1.0 years, female
      21 and male 9, mean valve area 0.7 +/- 3 mm(2)). Edwards SAPIEN heart valves, 23
      mm (21 patients) and 26 mm (9 patients), by the transfemoral approach were used
      in the TAVI procedures. All TAVI procedures were successful. Both QTd and LVMI at
      the 6(th) month after TAVI were significantly reduced compared with baseline
      values of QTd and LVMI before TAVI (73.8 +/- 4 ms vs. 68 +/- 2 ms, P = 0.001 and
      198 +/- 51 g/m(2) vs. 184 +/- 40 g/m(2), P = 0.04, respectively). There was a
      significant correlation between QTd and LVMI (r = 0.646, P < 0.001). CONCLUSIONS:
      QTd, which malign ventricular arrhythmia marker, and LVMI were significantly
      reduced after TAVI procedure. TAVI may decrease the possibility of ventricular
      arrhythmia in patients with aortic stenosis.

PMID- 25593577
TI  - Catheter ablation of atrial fibrillation in the elderly.
AB  - BACKGROUND: Atrial fibrillation (AF) catheter ablation has emerged as a promising
      treatment strategy for AF, but has not been widely adopted in the elderly
      population. The present study aimed to determine the safety and efficacy of AF
      catheter ablation in the elderly population. METHODS AND RESULTS: The study
      population consisted of 316 patients with paroxysmal AF who underwent left atrial
      ablation. Ninety-five patients were >= 65 years (48 males, mean age 68.9 +/- 3.0
      years old) and 221 patients were < 65 years old (130 males, mean age 52.5 +/-
      10.4 years old). After a mean follow-up period of 34.0 +/- 15.1 months, 55
      (57.9%) patients in the elderly group were free from arrhythmia recurrence
      compared with 149 (67.4%) patients in the younger group (P = 0.169). Procedural
      complications were uncommon in both study groups. In logistic regression
      analysis, left atrial diameter (P = 0.003), hypertension (P = 0.001),
      dyslipidemia (P = 0.039), and coronary artery disease (P = 0.018) were
      independent predictors of AF recurrence in the elderly population. CONCLUSIONS:
      Catheter ablation of AF is safe and effective in older patients. Invasive
      strategies should be considered as an alternative choice in symptomatic elderly
      patients with AF.

PMID- 25593578
TI  - High sensitivity C-reactive protein and cardfiac resynchronization therapy in
      patients with advanced heart failure.
AB  - BACKGROUND: The data on the prognostic values of high sensitivity C-reactive
      protein (hsCRP) levels in patients with advanced symptomatic heart failure (HF)
      receiving cardiac resynchronization therapy (CRT) are scarce. The aim of present
      study was to investigate the association of serum hsCRP levels with left
      ventricle reverse remodeling after six months of CRT as well as long-term
      outcome. METHODS: A total of 232 CRT patients were included. The assessment of
      hsCRP values, clinical status and echocardiographic data were performed at
      baseline and after six months of CRT. Long-term follow-up included all-cause
      mortality and hospitalizations for HF. RESULTS: During the mean follow-up periods
      of 31.3 +/- 31.5 months, elevated hsCRP (> 3 mg/L) prior to CRT was associated
      with a significant 2.39-fold increase (P = 0.006) in the risk of death or HF
      hospitalizations. At 6-month follow-up, patients who responded to CRT showed
      significant reductions or maintained low in hsCRP levels (-0.5 +/- 4.1 mg/L
      reduction) compared with non-responders (1.7 +/- 6.1 mg/L increase, P = 0.018).
      Compared with patients in whom 6-month hsCRP levels were reduced or remained low,
      patients in whom 6-month hsCRP levels were increased or maintained high
      experienced a significantly higher risk of subsequent death or HF
      hospitalizations (Log-rank P < 0.001). The echocardiographic improvement was also
      better among patients in whom 6-month hsCRP levels were reduced or remained low
      compared to those in whom 6-month hsCRP levels were raised or maintained high.
      CONCLUSIONS: Our findings demonstrated that measurement of baseline and follow-up
      hsCRP levels may be useful as prognostic markers for timely potential risk
      stratification and subsequent appropriate treatment strategies in patients with
      advanced HF undergoing CRT.

PMID- 25593579
TI  - Mediated protective effect of electroacupuncture pretreatment by miR-214 on
      myocardial ischemia/reperfusion injury.
AB  - BACKGROUND: Electroacupuncture pretreatment plays a protective role in myocardial
      ischemia/reperfusion (I/R) injury and microRNAs (miRNAs) could act on various
      facets of cardiac function. However, the role of miRNAs in the cardioprotection
      by electroacupuncture pretreatment on myocardial I/R injury remains unknown. The
      purpose of the study was to examine whether miR-214 was involved in
      cardioprotection by electroacupuncture. METHODS: Using rat myocardial I/R model,
      we examined the role of electroacupuncture pretreatment in myocardial I/R injury
      and analyzed the changes in the expression of miR-214. In addition, I/R was
      simulated in vitro by performing oxygen-glucose deprivation (OGD) on H9c2 cell
      cultures, and the effect of electroacupuncture pretreatment on I/R injury as well
      as expressional level of miR-214 were examined in vitro. Furthermore, the miR-214
      mimic was transfected into OGD-treated H9c2 cells, we analyzed the cell
      apoptosis, lactate dehydrogenase (LDH) and creatine kinase (CK) activities,
      intracellular free Ca(2+) concentration ([Ca(2+)]i) as well as the relative
      protein levels of sodium/calcium exchanger 1(NCX1), BCL2-like 11 (BIM),
      calmodulin-dependent protein kinase IIdelta (CaMKIIdelta) and Cyclophilin D
      (CypD). RESULTS: The in vivo results revealed that compared with the I/R group,
      the electroacupuncture pretreatment group showed significant decreased myocardial
      infarct size, as well as the increased indices of the cardiac function, including
      heart rate, mean arterial pressure, left ventricular systolic pressure and
      maximal rate for left ventricular pressure rising and declining (+/-dp/dt max).
      In addition, electroacupuncture pretreatment could inhibit the elevation of LDH
      and CK activities induced by I/R injury. The quantitative PCR (qPCR) results
      demonstrated electroacupuncture pretreatment could provide cardioprotection
      against myocardial I/R injury in rats with miR-214 up-regulation. In the
      meanwhile, in vitro, electroacupuncture pretreatment protected H9c2 cells from
      OGD-induced injury. Transfection of miR-214 mimic showed protective effects on
      OGD-induced injury to H9c2 cells by reducing apoptosis, decreasing LDH and CK
      activities, rescuing the OGD-induced Ca(2+) and down-regulating elevated protein
      levels of NCX1, BIM, CaMKIIdelta and CypD. CONCLUSIONS: Our findings firstly
      demonstrated that electroacupuncture pretreatment promotes the expression of miR
      214 in myocardial I/R injury and miR-214 contributes to the protective effect of
      electroacupuncture on myocardial I/R injury.

PMID- 25593580
TI  - Recombinant adeno-associated virus serotype 9 with p65 ribozyme protects H9c2
      cells from oxidative stress through inhibiting NF-kappaB signaling pathway.
AB  - BACKGROUND: Oxidative stress is a major mechanism underlying the pathogenesis of
      cardiovascular disease. It can trigger inflammatory cascades which are primarily
      mediated via nuclear factor-kappaB (NF-kappaB). The NF-kappaB transcription
      factor family includes several subunits (p50, p52, p65, c-Rel, and Rel B) that
      respond to myocardial ischemia. It has been proved that persistent myocyte NF
      kappaB p65 activation in heart failure exacerbates cardiac remodeling. MECHODS: A
      recombinant adeno-associated virus serotype 9 carrying enhanced green fluorescent
      protein and anti-NF-kappaB p65 ribozyme (AAV9-R65-CMV-eGFP) was constructed. The
      cells were assessed by MTT assay, Annexin V-propidium iodide dual staining to
      study apoptosis. The expression of P65 and P50 were assessed by Western blot to
      investigate the underlying molecular mechanisms. RESULTS: After stimulation with
      H2O2 for 6 h, H9c2 cells viability decreased significantly, a large fraction of
      cells underwent apoptosis. We observed a rescue of H9c2 cells from H2O2-induced
      apoptosis in pretreatment with AAV9-R65-CMV-eGFP. Moreover, AAV9-R65-CMV-eGFP
      decreased H2O2-induced P65 expression. CONCLUSIONS: AAV9-R65-CMV-eGFP protects
      H9c2 cells from oxidative stress induced apoptosis through down-regulation of P65
      expression. These observations indicate that AAV9-R65-CMV-eGFP has the potential
      to exert cardioprotective effects against oxidative stress, which might be of
      great importance to clinical efficacy for cardiovascular disease.

PMID- 25593581
TI  - Cognitive impairment in heart failure patients.
AB  - Cognitive damage in heart failure (HF) involves different domains thus
      interfering with the ability for single patient to self-care and to cope with
      treatment regimens, modifying symptoms and health behaviours. Many cerebral and
      functional changes were detected in brain imaging, involving areas of both grey
      and white matter deputed to cognition. Although various instruments are available
      to explore cognition, no consensus was obtained on better tools to be used in HF
      population. Reduction in cerebral blood flow, decreased cardiac output,
      alterations of cerebrovascular reactivity and modification of blood pressure
      levels are the main features involved in the etiopathogenetic mechanisms of
      cognitive deficit. Several cardiac variables, laboratory parameters, demographic
      and clinical elements were studied for their possible relation with cognition and
      should be properly evaluated to define patients at increased risk of impairment.
      The present review gathers available data pointing out assured information and
      discussing possible areas of research development. 

PMID- 25593582
TI  - Management of chronic heart failure in the older population.
AB  - Chronic heart failure (CHF) is the leading cause of hospitalization for those
      over the age of 65 and represents a significant clinical and economic burden.
      About half of hospital re-admissions are related to co-morbidities, polypharmacy
      and disabilities associated with CHF. Moreover, CHF also has an enormous cost in
      terms of poor prognosis with an average one year mortality of 33%-35%. While more
      than half of patients with CHF are over 75 years, most clinical trials have
      included younger patients with a mean age of 61 years. Inadequate data makes
      treatment decisions challenging for the providers. Older CHF patients are more
      often female, have less cardiovascular diseases and associated risk factors, but
      higher rates of non-cardiovascular conditions and diastolic dysfunction. The
      prevalence of CHF with reduced ejection fraction, ischemic heart disease, and its
      risk factors declines with age, whereas the prevalence of non-cardiac co
      morbidities, such as chronic renal failure, dementia, anemia and malignancy
      increases with age. Diabetes and hypertension are among the strongest risk
      factors as predictors of CHF particularly among women with coronary heart
      disease. This review paper will focus on the specific consideration for CHF
      assessment in the older population. Management strategies will be reviewed,
      including non-pharmacologic, pharmacologic, quality care indicators, quality
      improvement in care transition and lastly, end-of-life issues. Palliative care
      should be an integral part of an interdisciplinary team approach for a
      comprehensive care plan over the whole disease trajectory. In addition, frailty
      contributes valuable prognostic insight incremental to existing risk models and
      assists clinicians in defining optimal care pathways for their patients. 

PMID- 25593585
TI  - Leiomyosarcoma with coronary fistulae and ventricular septal perforation: A case
      study.
AB  - Coronary fistulae and ventricular septal perforation are very rare clinically,
      and even less caused by cardiac leiomyosarcoma. A case is reported that a 67-year
      old female had cardiac leiomyosarcoma with progressive heart failure and coronary
      fistulae and ventricular septal perforation. This case was special since all ante
      mortem examinations and cardiac surgery failed to detect the presence of any
      abnormal cardiac mass. Therefore, the malignant cardiac tumors could appear in an
      invasive form without mass and be one of the causes of the coronary fistulae and
      ventricular septal perforation. 

PMID- 25593584
TI  - Simple mechanical thrombectomy with intrapulmonary arterial thrombolysis in
      pulmonary thromboembolism: a small case series.
AB  - Pulmonary thromboembolism (PTE) is a life-threatening condition with a high early
      mortality rate caused by acute right ventricular failure and cardiogenic shock.
      We report a series of three patients who presented with acute and subacute
      submassive PTE. They were successfully treated by simple catheter-based
      mechanical thrombectomy and intrapulmonary arterial thrombolysis. Mechanical
      fragmentation and aspiration of thrombus was performed by commonly used J-wire,
      multi-purpose and Judkin Right guiding catheters and this obviated the need of
      specific thrombectomy devices. 

PMID- 25593583
TI  - The role and modulation of autophagy in experimental models of myocardial
      ischemia-reperfusion injury.
AB  - A physiological sequence called autophagy qualitatively determines cellular
      viability by removing protein aggregates and damaged cytoplasmic constituents,
      and contributes significantly to the degree of myocardial ischemia-reperfusion
      (I/R) injury. This tightly orchestrated catabolic cellular 'housekeeping' process
      provides cells with a new source of energy to adapt to stressful conditions. This
      process was first described as a pro-survival mechanism, but increasing evidence
      suggests that it can also lead to the demise of the cell. Autophagy has been
      implicated in the pathogenesis of multiple cardiac conditions including
      myocardial I/R injury. However, a debate persists as to whether autophagy acts as
      a protective mechanism or contributes to the injurious effects of I/R injury in
      the heart. This controversy may stem from several factors including the
      variability in the experimental models and species, and the methodology used to
      assess autophagy. This review provides updated knowledge on the modulation and
      role of autophagy in isolated cardiac cells subjected to I/R, and the growing
      interest towards manipulating autophagy to increase the survival of cardiac
      myocytes under conditions of stress-most notably being I/R injury. Perturbation
      of this evolutionarily conserved intracellular cleansing autophagy mechanism, by
      targeted modulation through, among others, mammalian target of rapamycin (mTOR)
      inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators,
      calcium lowering agents, resveratrol, longevinex, sirtuin activators, the
      proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to
      heart cells against I/R induced cell death. Thus, therapeutic manipulation of
      autophagy in the challenged myocardium may benefit post-infarction cardiac
      healing and remodeling. 

PMID- 25593586
TI  - Cardiac resynchronization therapy for heart failure induced by left bundle branch
      block after transcatheter closure of ventricular septal defect.
AB  - A 54-year-old female patient with congenital heart disease had a persistent
      complete left bundle branch block three months after closure by an Amplatzer
      ventricular septal defect occluder. Nine months later, the patient suffered from
      chest distress, palpitation, and sweating at daily activities, and her 6-min walk
      distance decreased significantly (155 m). Her echocardiography showed increased
      left ventricular end-diastolic diameter with left ventricular ejection fraction
      of 37%. Her symptoms reduced significantly one week after received cardiac
      resynchronization therapy. She had no symptoms at daily activities, and her echo
      showed left ventricular ejection fraction of 46% and 53%. Moreover, left
      ventricular end-diastolic diameter decreased 6 and 10 months after cardiac
      resynchronization therapy, and 6-min walk distance remarkably increased. This
      case demonstrated that persistent complete left bundle branch block for nine
      months after transcatheter closure with ventricular septal defect Amplatzer
      occluder could lead to left ventricular enlargement and a significant decrease in
      left ventricular systolic function. Cardiac resynchronization therapy decreased
      left ventricular end-diastolic diameter and increased left ventricular ejection
      fraction, thereby improving the patient's heart functions. 

PMID- 25593587
TI  - Can post-mortem computed tomography be considered an alternative for autopsy in
      deaths due to hemopericardium?
AB  - Hemopericardium is a common finding at autopsy, but it may represent a challenge
      for the forensic pathologist when the etiopathological relationship in causing
      death is requested. Hemopericardium and cardiac tamponade can be evaluated in
      living people using radiological techniques, in particular computer tomography
      (CT). Only a few studies are reported in literature involving post-mortem (PM)
      cases, where PMCT imaging has been used in order to investigate acute
      hemopericardium, and they have shown a good accuracy of this technique. Here we
      report a case involving a 70-year-old white male found dead on the beach, with a
      medical history of hepatitis C and chronic hypertension with a poor
      pharmacological response. A PMCT was performed about 3 h after the discovery of
      the body. The PMCT examination showed an intrapericardial aortic dissection
      associated to a periaortic hematoma, a sickle-shaped intramural hematoma, a false
      lumen, and a hemopericardium consisting in fluid and clotted blood. In this case,
      the PMCT was able to identify the cause of death, even though a traditional
      autopsy was required to confirm the radiological findings. PMCT is a reliable
      technique, which in chosen cases, can be performed without the need for a
      traditional autopsy to be carried out. 

PMID- 25593589
TI  - Enhanced activity of cyclic transporter sequences driven by phase behavior of
      peptide-lipid complexes.
AB  - We demonstrate that recent observed increases in cell permeation activity of
      cyclic peptides via transporter sequences is due to the underlying phase behavior
      of peptide-lipid complexes and its relation to the topological requirement of
      membrane permeation. We also show how these effects can be amplified by
      incorporating hydrophobicity in these sequences.

PMID- 25593591
TI  - Stopping outbreaks with real-time genomic epidemiology.
AB  - One of the most successful public health applications of next-generation
      sequencing is whole-genome sequencing of pathogens to not only detect and
      characterize outbreaks, but also to inform outbreak management. Using genomics,
      infection control teams can now track, with extraordinarily high resolution, the
      transmission events within outbreaks, opening up possibilities for targeted
      interventions. These successes are positioning the emerging field of genomic
      epidemiology to replace traditional molecular epidemiology, and increasing our
      ability to limit the spread of multidrug-resistant organisms. 

PMID- 25593590
TI  - Engineering a Streptomyces coelicolor biosynthesis pathway into Escherichia coli
      for high yield triglyceride production.
AB  - BACKGROUND: Microbial lipid production represents a potential alternative
      feedstock for the biofuel and oleochemical industries. Since Escherichia coli
      exhibits many genetic, technical, and biotechnological advantages over native
      oleaginous bacteria, we aimed to construct a metabolically engineered E. coli
      strain capable of accumulating high levels of triacylglycerol (TAG) and evaluate
      its neutral lipid productivity during high cell density fed-batch fermentations.
      RESULTS: The Streptomyces coelicolor TAG biosynthesis pathway, defined by the
      acyl-CoA:diacylglycerol acyltransferase (DGAT) Sco0958 and the phosphatidic acid
      phosphatase (PAP) Lppbeta, was successfully reconstructed in an E. coli
      diacylglycerol kinase (dgkA) mutant strain. TAG production in this genetic
      background was optimized by increasing the levels of the TAG precursors,
      diacylglycerol and long-chain acyl-CoAs. For this we carried out a series of
      stepwise optimizations of the chassis by 1) fine-tuning the expression of the
      heterologous SCO0958 and lppbeta genes, 2) overexpression of the S. coelicolor
      acetyl-CoA carboxylase complex, and 3) mutation of fadE, the gene encoding for
      the acyl-CoA dehydrogenase that catalyzes the first step of the beta-oxidation
      cycle in E. coli. The best producing strain, MPS13/pET28-0958-ACC/pBAD-LPPbeta
      rendered a cellular content of 4.85% cell dry weight (CDW) TAG in batch
      cultivation. Process optimization of fed-batch fermentation in a 1-L stirred-tank
      bioreactor resulted in cultures with an OD600nm of 80 and a product titer of
      722.1 mg TAG L(-1) at the end of the process. CONCLUSIONS: This study represents
      the highest reported fed-batch productivity of TAG reached by a model non
      oleaginous bacterium. The organism used as a platform was an E. coli BL21
      derivative strain containing a deletion in the dgkA gene and containing the TAG
      biosynthesis genes from S. coelicolor. The genetic studies carried out with this
      strain indicate that diacylglycerol (DAG) availability appears to be one of the
      main limiting factors to achieve higher yields of the storage compound.
      Therefore, in order to develop a competitive process for neutral lipid production
      in E. coli, it is still necessary to better understand the native regulation of
      the carbon flow metabolism of this organism, and in particular, to improve the
      levels of DAG biosynthesis.

PMID- 25593588
TI  - OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS.
AB  - Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably
      less ototoxic than cisplatin. While common laboratory species such as mice,
      guinea pigs and rats are highly resistant to carboplatin ototoxicity, the
      chinchilla stands out as highly susceptible. Moreover, carboplatin causes an
      unusual gradient of cell death in chinchillas. Moderate doses selectively damage
      type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion
      tends to be relatively uniform along the length of the cochlea. Higher doses
      eventually damage outer hair cells (OHC), but the lesion follows the traditional
      gradient in which damage is more severe in the base than the apex. While
      carboplatin ototoxicity has been well documented in adult animals in vivo, little
      is known about its in vitro toxicity. To elucidate the ototoxic effects of
      carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures
      from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and
      vestibular cultures were treated with carboplatin concentrations ranging from 50
      uM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively
      damaged IHC at low concentrations (50-100 uM). Surprisingly, IHC loss decreased
      at higher doses and IHC were intact at doses exceeding 500 uM. The mechanisms
      underlying this nonlinear response are unclear but could be related to a decrease
      in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the
      cochlea, the carboplatin dose-response function increased with dose with the
      highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells
      and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by
      carboplatin concentrations <10 uM; however, the damage in OHC were more severe
      than IHC once the dose reached 100 uM. A dose at 500 uM destroyed all the
      cochlear hair cells, but hair cell loss decreased at high concentrations and
      nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike
      the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve
      fiber and spiral ganglion losses increased with doses above 50 uM with the
      highest dose destroying virtually all SGN. The remarkable species differences
      seen in vitro suggest that chinchilla IHC and type I SGN posse some unique
      biological mechanism that makes them especially vulnerable to carboplatin
      toxicity.

PMID- 25593592
TI  - Genomics and infectious disease: a call to identify the ethical, legal and social
      implications for public health and clinical practice.
AB  - Advances in genomics are contributing to the development of more effective,
      personalized approaches to the prevention and treatment of infectious diseases.
      Genetic sequencing technologies are furthering our understanding of how human and
      pathogen genomic factors - and their interactions - contribute to individual
      differences in immunologic responses to vaccines, infections and drug therapies.
      Such understanding will influence future policies and procedures for infectious
      disease management. With the potential for tailored interventions for particular
      individuals, populations or subpopulations, ethical, legal and social
      implications (ELSIs) may arise for public health and clinical practice. Potential
      considerations include balancing health-related benefits and harms between
      individuals and the larger community, minimizing threats to individual privacy
      and autonomy, and ensuring just distribution of scarce resources. In this
      Opinion, we consider the potential application of pathogen and host genomic
      information to particular viral infections that have large-scale public health
      consequences but differ in ELSI-relevant characteristics such as ease of
      transmission, chronicity, severity, preventability and treatability. We argue for
      the importance of anticipating these ELSI issues in advance of new scientific
      discoveries, and call for the development of strategies for identifying and
      exploring ethical questions that should be considered as clinical, public health
      and policy decisions are made. 

PMID- 25593593
TI  - Characterizing the genetic basis of bacterial phenotypes using genome-wide
      association studies: a new direction for bacteriology.
AB  - Genome-wide association studies (GWASs) have become an increasingly important
      approach for eukaryotic geneticists, facilitating the identification of hundreds
      of genetic polymorphisms that are responsible for inherited diseases. Despite the
      relative simplicity of bacterial genomes, the application of GWASs to identify
      polymorphisms responsible for important bacterial phenotypes has only recently
      been made possible through advances in genome sequencing technologies. Bacterial
      GWASs are now about to come of age thanks to the availability of massive
      datasets, and because of the potential to bridge genomics and traditional genetic
      approaches that is provided by improving validation strategies. A small number of
      pioneering GWASs in bacteria have been published in the past 2 years, examining
      from 75 to more than 3,000 strains. The experimental designs have been diverse,
      taking advantage of different processes in bacteria for generating variation.
      Analysis of data from bacterial GWASs can, to some extent, be performed using
      software developed for eukaryotic systems, but there are important differences in
      genome evolution that must be considered. The greatest experimental advantage of
      bacterial GWASs is the potential to perform downstream validation of causality
      and dissection of mechanism. We review the recent advances and remaining
      challenges in this field and propose strategies to improve the validation of
      bacterial GWASs. 

PMID- 25593596
TI  - The emerging need for family-centric initiatives for obtaining consent in
      personal genome research.
AB  - The use of information and communication technology can offer a novel way to
      promote family-centric initiatives for informed consent, and can address
      associated ethical challenges in personal genome research. 

PMID- 25593595
TI  - Virus-host interactomics: new insights and opportunities for antiviral drug
      discovery.
AB  - The current therapeutic arsenal against viral infections remains limited, with
      often poor efficacy and incomplete coverage, and appears inadequate to face the
      emergence of drug resistance. Our understanding of viral biology and
      pathophysiology and our ability to develop a more effective antiviral arsenal
      would greatly benefit from a more comprehensive picture of the events that lead
      to viral replication and associated symptoms. Towards this goal, the construction
      of virus-host interactomes is instrumental, mainly relying on the assumption that
      a viral infection at the cellular level can be viewed as a number of
      perturbations introduced into the host protein network when viral proteins make
      new connections and disrupt existing ones. Here, we review advances in
      interactomic approaches for viral infections, focusing on high-throughput
      screening (HTS) technologies and on the generation of high-quality datasets. We
      show how these are already beginning to offer intriguing perspectives in terms of
      virus-host cell biology and the control of cellular functions, and we conclude by
      offering a summary of the current situation regarding the potential development
      of host-oriented antiviral therapeutics. 

PMID- 25593597
TI  - Host genes and their effect on the intestinal microbiome garden.
AB  - We are only beginning to understand the relationship between host genetics and
      the gut microbiome. Two recent studies help to disentangle this interaction and
      show that genetic loci across the human genome shape the gut microbiome. This
      opens the possibility that an unexpected number of genetic factors act directly
      on microbial composition and function to modulate immune pathways and metabolic
      phenotypes in host physiology and disease. 

PMID- 25593599
TI  - From transcriptional regulation to drugging the cancer epigenome.
AB  - Jay Bradner discusses the opportunities and challenges for the study and
      therapeutic targeting of the cancer epigenome, as well as innovative approaches
      to drug discovery. 

PMID- 25593598
TI  - Variants of uncertain significance in BRCA: a harbinger of ethical and policy
      issues to come?
AB  - After two decades of genetic testing and research, the BRCA1 and BRCA2 genes are
      two of the most well-characterized genes in the human genome. As a result,
      variants of uncertain significance (VUS; also called variants of unknown
      significance) are reported less frequently than for genes that have been less
      thoroughly studied. However, VUS continue to be uncovered, even for BRCA1/2. The
      increasing use of multi-gene panels and whole-genome and whole-exome sequencing
      will lead to higher rates of VUS detection because more genes are being tested,
      and most genomic loci have been far less intensively characterized than BRCA1/2.
      In this article, we draw attention to ethical and policy-related issues that will
      emerge. Experience garnered from BRCA1/2 testing is a useful introduction to the
      challenges of detecting VUS in other genetic testing contexts, while features
      unique to BRCA1/2 suggest key differences between the BRCA experience and the
      current challenges of multi-gene panels in clinical care. We propose lines of
      research and policy development, emphasizing the importance of pooling data into
      a centralized open-access database for the storage of gene variants to improve
      VUS interpretation. In addition, establishing ethical norms and regulated
      practices for sharing and curating data, analytical algorithms, interpretive
      frameworks and patient re-contact are important policy areas. 

PMID- 25593594
TI  - Clinical detection and characterization of bacterial pathogens in the genomics
      era.
AB  - The availability of genome sequences obtained using next-generation sequencing
      (NGS) has revolutionized the field of infectious diseases. Indeed, more than
      38,000 bacterial and 5,000 viral genomes have been sequenced to date, including
      representatives of all significant human pathogens. These tremendous amounts of
      data have not only enabled advances in fundamental biology, helping to understand
      the pathogenesis of microorganisms and their genomic evolution, but have also had
      implications for clinical microbiology. Here, we first review the current
      achievements of genomics in the development of improved diagnostic tools,
      including those that are now available in the clinic, such as the design of PCR
      assays for the detection of microbial pathogens, virulence factors or antibiotic
      resistance determinants, or the design of optimized culture media for
      'unculturable' pathogens. We then review the applications of genomics to the
      investigation of outbreaks, either through the design of genotyping assays or the
      direct sequencing of the causative strains. Finally, we discuss how genomics
      might change clinical microbiology in the future. 

PMID- 25593600
TI  - Toward evidence-based approach to deep venous thrombosis.

PMID- 25593601
TI  - The Saudi clinical practice guideline for the diagnosis of the first deep venous
      thrombosis of the lower extremity.
AB  - The diagnosis of deep venous thrombosis (DVT) may be challenging due to the
      inaccuracy of clinical assessment and diversity of diagnostic tests. On one hand,
      missed diagnosis may result in life-threatening conditions. On the other hand,
      unnecessary treatment may lead to serious complications. As a result of an
      initiative of the Ministry of Health of the Kingdom of Saudi Arabia (KSA), an
      expert panel led by the Saudi Association for Venous Thrombo-Embolism (SAVTE; a
      subsidiary of the Saudi Thoracic Society) with the methodological support of the
      McMaster University Working Group, produced this clinical practice guideline to
      assist healthcare providers in evidence-based clinical decision-making for the
      diagnosis of a suspected first DVT of the lower extremity. Twenty-four questions
      were identified and corresponding recommendations were made following the Grading
      of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
      These recommendations included assessing the clinical probability of DVT using
      Wells criteria before requesting any test and undergoing a sequential diagnostic
      evaluation, mainly using highly sensitive D-dimer by enzyme-linked immunosorbent
      assay (ELISA) and compression ultrasound. Although venography is the reference
      standard test for the diagnosis of DVT, its use was not recommended. 

PMID- 25593602
TI  - Evaluation of efficacy of non-invasive ventilation in Non-COPD and non-trauma
      patients with acute hypoxemic respiratory failure: A systematic review and meta
      analysis.
AB  - Non-invasive ventilation (NIV) has been widely supported in the past two decades
      as an effective application in avoiding the need for endotracheal intubation
      (ETI) and reducing associated mortality in acute hypoxemic respiratory failure
      (AHRF) patients. However, the efficacy of NIV in AHRF patients, non-related to
      chronic obstructive pulmonary disease (COPD) and trauma is still controversial in
      the field of medical research. This retrospective study aimed to evaluate the
      efficacy of NIV as an adjunctive therapy in non-COPD and non-traumatic AHRF
      patients. Data of 11 randomized control trials (RCTs), which were conducted
      between 1990 and 2010 to determine the efficacy of NIV in non-COPD and non
      traumatic AHRF patients, were reviewed from the PUBMED, MEDLINE, Cochrane
      Library, and EMBASE databases. Parameters monitored in this study included the
      ETI rate, fatal complications, mortality rate of patients, and their ICU and
      hospital duration of stay. Overall results showed a statistically significant
      decrease in the rate of ETI, mortality, and fatal complications along with
      reduced ICU and hospital length of stay in non-COPD and non-trauma AHRF patients
      of various etiologies. This systematic review suggests that non-COPD and non
      trauma AHRF patients can potentially benefit from NIV as compared with
      conventional treatment methods. Observations from various cohort studies,
      observational studies, and previously published literature advocate on the
      efficacy of NIV for treating non-COPD and non-traumatic AHRF patients. However,
      considering the diversity of studied populations, further studies and more
      specific trials on less heterogeneous AHRF patient groups are needed to focus on
      this aspect. 

PMID- 25593603
TI  - The effect of adding gender item to Berlin Questionnaire in determining
      obstructive sleep apnea in sleep clinics.
AB  - BACKGROUND AND AIM: We aimed to validate the Turkish version of Berlin
      Questionnaire (BQ) and developped a BQ-gender (BQ-G) form by adding gender
      component. We aimed to compare the two forms in defining patients with moderate
      to severe obstructive sleep apnea (OSA) in sleep clinics. METHODS: Four hundred
      and eighty five consecutive patients, refered to our sleep clinic for snoring,
      witnessed apnea and/or excessive daytime sleepiness were enrolled to the study.
      All patients underwent in-laboratory polysomnography (PSG). Patients with sleep
      efficiency less than 40% and total sleep time less than 4 hours, chronic
      anxiolitic/sedative drug usage, respiratory tract infection within past two weeks
      were excluded from the study. All the patients fulfilled BQ. The test and retest
      for BQ were applied in 15-day interval in 30 patients. RESULTS: Totally 433
      patients were enrolled to the study (285 male, 148 female). The mean age of the
      patients was 47,5 +/- 10.5 (21-79). 180 patients (41.6%) had apnea-hypopnea index
      (AHI) <= 15, while 253 patients (58,4%) had AHI > 15. The kappa value was 48-94
      and the the truth value was 69-94% for the test-retest procedure. Sensitivity,
      specificity, negative predictive value (NPV), positive predictive value (PPV),
      and area under the curve AUC were 84.2%, 31.7%, 48.7%, 63.4%, and 0.579 in order
      for BQ and 79.9 %, 51.7%, 63.2% , 69.6%, and 0.652 for BQ-G. CONCLUSION: The
      results showed that BQ-G is relatively better than BQ in determining moderate to
      severe OSA in sleep clinics where most of the patients are sleep apneic but both
      of the tests were found to have insufficient validities in defining moderate to
      severe OSA in sleep clinics.

PMID- 25593604
TI  - The effect of sand storms on acute asthma in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: Major sand storms are frequent in the Middle East. This study aims to
      investigate the role of air particulate matter (PM) level in acute asthma in
      children in Riyadh, Saudi Arabia. METHODS: An aerosol spectrometer was used to
      evaluate PM < 10MUm in diameter (PM10) and PM < 2.5 MUm in diameter (PM2.5)
      concentrations in the air every 30 minutes throughout February and March 2012 in
      Riyadh. Data on children 2-12 years of age presenting to the emergency department
      of a major children's hospital with acute asthma during the same period were
      collected including their acute asthma severity score. RESULTS: The median with
      interquartile range (IQR) levels of PM10 and PM2.5 were 454 MUg/m(3) (309,864)
      and 108 MUg/m(3) (72,192) respectively. There was no correlation between the
      average daily PM10 levels and the average number of children presenting with
      acute asthma per day (r = -0.14, P = 0.45), their daily asthma score (r = 0.014,
      P = 0.94), or admission rate ( r= -0.08, P = 0.65). This was also true for
      average daily PM2.5 levels. In addition, there was no difference in these
      variables between days with PM10 >1000 MUg/m(3), representing major sand storms,
      plus the following 5 days and other days with PM10< 1000 MUg/m(3). CONCLUSION:
      Sand storms, even major ones, had no significant impact on acute asthma
      exacerbations in children in Riyadh, Saudi Arabia. The very high levels of PM,
      however, deserve further studying especially of their long-term effects.

PMID- 25593605
TI  - Impact of multimedia information on bronchoscopy procedure: is it really helpful?
AB  - AIM: In this study, we aimed to investigate the effect of written informed
      consent and comprehensive multimedia information on the anxiety level of
      patients, consumption of sedatives, difficulties during bronchoscopy,
      complications and duration of procedure. METHODS: 150 patients undergoing
      bronchoscopy were included to this study. They were randomized into two groups
      Multimedia information group (MIG, n = 75) and written-informed consent group
      (WICG, n = 75)). Signed written informed consent was obtained from all patients.
      Patients in MIG group watched comprehensive multimedia presentation. State
      anxiety scores of all patients were evaluated with State and Trait anxiety
      inventory (STAI-S). RESULTS: STAI-S score of patients in MIG (40.31 +/- 8.08) was
      lower than patients in WICG (44.29 +/- 9.62) (P = 0.007). Satisfaction level was
      higher in MIG (P = 0.001). Statistically higher difficulties during passage
      through vocal cords and interventions during bronchoscopy were present in WICG
      group (P = 0.013 and P = 0.043, respectively). Total midazolam dose during
      bronchoscopy, and duration of bronchoscopy were statistically lower in MIG
      patients (P < 0.001 and P = 0.045, respectively). Difficulties during waiting
      period, passage through nasal/oral route, applications of local anesthesia and
      complication frequency were similar in both groups. CONCLUSION: Besides reducing
      the state anxiety, multimedia information can reduce the dose of sedation,
      shorten the processing duration and reduce the difficulties during bronchoscopy.

PMID- 25593606
TI  - Pirfenidone treatment in idiopathic pulmonary fibrosis: A Saudi experience.
AB  - BACKGROUND: Recent trials involving pirfenidone suggest a beneficial effect in
      the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To report on the
      efficacy and safety of pirfenidone in the treatment of patients with IPF, at a
      tertiary care hospital in Saudi Arabia. METHODS: The study included 58 patients
      with IPF who were evaluated from March 2012 to March 2013. During the study
      period, 33 patients received pirfenidone, and the remaining patients (n = 25)
      served as a control group. Baseline clinical characteristics, physiological
      parameters and the results of a 36-Item Short Form Health Survey (SF-36) were
      compared between the groups. Furthermore, we compared changes in forced vital
      capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLco), six
      minute walk distance (6MWD) and SF-36 for both groups during follow-up. The last
      follow-up period ended in January 2014. RESULTS: There were no significant
      differences in baseline clinical characteristics between the groups. Furthermore,
      we found no differences in FVC, DLco and SF-36 during follow-up (median, 12
      months). However, patients receiving pirfenidone treatment were less likely to
      experience reductions in 6MWD compared with the control group (13% vs. 52%,
      respectively; P = 0.001). Although adverse events were more frequently reported
      by the pirfenidone group compared with the control group (85 vs. 56%,
      respectively; P = 0.015), these patients did not require discontinuation of
      treatment. CONCLUSION: Pirfenidone treatment preserves functional capacity, as
      reflected by the 6MWD. Adverse events associated with pirfenidone treatment were
      generally well tolerated by the patients.

PMID- 25593607
TI  - Sonographic evaluation of intravascular volume status: Can internal jugular or
      femoral vein collapsibility be used in the absence of IVC visualization?
AB  - INTRODUCTION: Inferior vena cava collapsibility index (IVC-CI) has been shown to
      correlate with both clinical and invasive assessment of intravascular volume
      status, but has important limitations such as the requirement for advanced
      sonographic skills, the degree of difficulty in obtaining those skills, and often
      challenging visualization of the IVC in the postoperative patient. The current
      study aims to explore the potential for using femoral (FV) or internal jugular
      (IJV) vein collapsibility as alternative sonographic options in the absence of
      adequate IVC visualization. METHODS: A prospective, observational study comparing
      IVC-CI and Fem- and/or IJV-CI was performed in two intensive care units (ICU)
      between January 2012 and April 2014. Concurrent M-mode measurements of IVC-CI and
      FV- and/or IJV-CI were collected during each sonographic session. Measurements of
      IVC were obtained using standard technique. IJV-CI and FV-CI were measured using
      high-frequency, linear array ultrasound probe placed in the corresponding
      anatomic areas. Paired data were analyzed using coefficient of
      correlation/determination and Bland-Altman determination of measurement bias.
      RESULTS: We performed paired ultrasound examination of IVC-IJV (n = 39) and IVC
      FV (n = 22), in 40 patients (mean age 54.1; 40% women). Both FV-CI and IJV-CI
      scans took less time to complete than IVC-CI scans (both, P < 0.02). Correlations
      between IVC-CI/FV-CI (R(2) = 0.41) and IVC-CI/IJV-CI (R(2) = 0.38) were weak.
      There was a mean -3.5% measurement bias between IVC-CI and IJV-CI, with trend
      toward overestimation for IJV-CI with increasing collapsibility. In contrast, FV
      CI underestimated collapsibility by approximately 3.8% across the measured
      collapsibility range. CONCLUSION: Despite small measurement biases, correlations
      between IVC-CI and FV-/IJV-CI are weak. These results indicate that IJ-CI and FV
      CI should not be used as a primary intravascular volume assessment tool for
      clinical decision support in the ICU. The authors propose that IJV-CI and FV-CI
      be reserved for clinical scenarios where sonographic acquisition of both IVC-CI
      or subclavian collapsibility are not feasible, especially when trended over time.
      Sonographers should be aware that IJV-CI tends to overestimate collapsibility
      when compared to IVC-CI, and FV-CI tends to underestimates collapsibility
      relative to IVC-CI.

PMID- 25593608
TI  - Conventional transbronchial needle aspiration: From acquisition to precision.
AB  - INTRODUCTION: Conventional transbronchial needle aspiration (C-TBNA) is a
      minimally invasive, safe, and cost-effective technique in evaluating mediastinal
      lymphadenopathy. Previously we reported that the skills for C-TBNA can be
      acquired from the books. We studied the learning curve for C-TBNA for a single
      bronchoscopist at a tertiary-care center where ultrasound technology remains
      difficult to acquire . METHODS: We prospectively collected results of the first
      99 consecutively performed C-TBNA between December 2009 and 2013. Patients were
      divided into 3 groups: (I): First 33, (II): Next 33 and (III): Last 33. Results
      were categorized as malignant, non-malignant or non-diagnostic. Diagnostic yield
      (DY), sensitivity (SEN), specificity (SPE), positive and negative predictive
      values (PPV, NPV), and accuracy (ACC) were calculated to learn the learning curve
      for C-TBNA. RESULTS: Total 99 patients (M:F = 62:37), mean age 58.2 +/- 11.5
      years, mean LN diameter 26.9 +/- 9.8 mm underwent C-TBNA. Sixty-nine patients had
      lymph nodes (LNs) >20 mm in diameter. Final diagnoses were established by C-TBNA
      in 44 (yield 44.4%), mediastinoscopy 47, transthoracic needle aspiration 5,
      endobronchial biopsy 2 and peripheral LN biopsy 1. C-TBNA was exclusively
      diagnostic in 35.4%. Group I: DY: 42.4%, 64.7% in malignancies, 19% in benign
      conditions (P = 0.008). SEN, SPE, PPV, NPV, ACC = 70%, 100%, 100%, 66.6%, 78.7%,
      respectively. Group II: DY: 54.5% (36.4% exclusive), 88.2% in malignancies and
      19% benign conditions (P = 0.000). SEN, SPE, PPV, NPV, ACC=72%, 100%, 100%,
      53.3%, 78.7%, respectively. Group III: DY: 36.3% (27% exclusive), 100% in
      malignancies and 16% in benign conditions. SEN, SPE, PPV, NPV, ACC = 92.3%, 100%,
      100%, 95.2%, 97%, respectively. No difference was found in relation to LN size or
      location and TBNA yield. CONCLUSION: C-TBNA can be easily learned and the
      proficiency can be attained with <66 procedures. In selected patients, its
      exclusivity could exceed 35%.

PMID- 25593609
TI  - Status of respiratory care profession in Saudi Arabia: A national survey.
AB  - BACKGROUND: Respiratory care (RC) is an allied health profession that involves
      assessing and treating patients who have pulmonary diseases. Research indicates
      that respiratory therapists' (RT's) involvement in caring for patients with
      respiratory disorders improves important outcome measures. In Kingdome of Saudi
      Arabia (KSA), RC has been practiced by RTs for more than 30 years. OBJECTIVE: We
      sought to investigate the status of the RC workforce in Saudi Arabia in terms of
      demographic distribution, number, education, and RC service coverage. METHODS: We
      used a specially designed survey to collect data. A list of 411 working hospitals
      in KSA was obtained. All hospitals were contacted to inquire if RC is practiced
      by RTs. Data were collected from hospitals that employ RTs. RESULTS: Only 88
      hospitals, 21.4% of total hospitals in the country, have RTs. Out of the 244
      Ministry of Health (MOH) hospitals, only 31 hospitals (12.7%) employ RTs. There
      are 1,477 active RTs in KSA. Twenty-five percent of them, or 371, are Saudis. The
      majority of the RT workforce (60%) work for non-MOH government hospitals, and
      almost half the total RTs work in Riyadh province. About 60% of RTs work in
      critical care settings. RC coverage of critical care was 44.5% of ideal. The
      overall RT-to-ICU bed ratio was 1:11. The ratio was 1:9 for non-MOH government
      hospitals, and 1:20 for MOH hospitals. CONCLUSIONS: We report the first
      insightful data on RC workforce in KSA. These data should be used by educational
      institutions and health policy makers to plan better RC coverage in the country.

PMID- 25593611
TI  - Novel technique in managing bronchobiliary fistula in adults: Endobronchial
      embolization using silicone spigots in 2 cases.
AB  - Bronchobiliary fistula (BBF) can complicate most hepatic pathologies. This is a
      challenging group of patients, especially when surgery is precluded. The
      bronchoscopic application of silicon spigots is a recognized technique for the
      treatment of massive hemoptysis and the management of patients with
      bronchopleural fistula following lung resection. Their role in the treatment of
      BBF has never been described. In this paper we report the successful embolization
      using silicon spigots in two patients with BBF secondary to malignant disease,
      when all surgical options were exhausted. 

PMID- 25593610
TI  - Progression-free survival, post-progression survival, and tumor response as
      surrogate markers for overall survival in patients with extensive small cell lung
      cancer.
AB  - OBJECTIVES: The effects of first-line chemotherapy on overall survival (OS) might
      be confounded by subsequent therapies in patients with small cell lung cancer
      (SCLC). We examined whether progression-free survival (PFS), post-progression
      survival (PPS), and tumor response could be valid surrogate endpoints for OS
      after first-line chemotherapies for patients with extensive SCLC using individual
      level data. METHODS: Between September 2002 and November 2012, we analyzed 49
      cases of patients with extensive SCLC who were treated with cisplatin and
      irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor
      response with OS were analyzed at the individual level. RESULTS: Spearman rank
      correlation analysis and linear regression analysis showed that PPS was strongly
      correlated with OS (r = 0.97, p < 0.05, R(2)= 0.94), PFS was moderately
      correlated with OS (r = 0.58, p < 0.05, R(2)= 0.24), and tumor shrinkage was
      weakly correlated with OS (r = 0.37, p < 0.05, R(2)= 0.13). The best response to
      second-line treatment, and the number of regimens employed after progression
      beyond first-line chemotherapy were both significantly associated with PPS ( p <=
      0.05). CONCLUSION: PPS is a potential surrogate for OS in patients with extensive
      SCLC. Our findings also suggest that subsequent treatment after disease
      progression following first-line chemotherapy may greatly influence OS.

PMID- 25593612
TI  - Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess.
AB  - Cystic fibrosis (CF) and apparent mineralocorticoid excess (AME) syndrome are
      both autosomal recessive disorders that result from mutations of specific
      identified genes for each condition. CF is caused by defects in the Cystic
      fibrosis trans membrane conductance regulator (CFTR) gene which encodes for a
      protein that functions as a chloride channel and regulates the flow of other ions
      across the apical surface of epithelial cells. AME is due to the deficiency of
      11beta-hydroxysteroid dehydrogenase type 2 enzyme (11betaHSD2), which is
      responsible for the peripheral inactivation of cortisol to cortisone. Cortisol
      excess stimulates the mineralocoritoid receptors (MR) resulting in intense sodium
      retention, hypokalemia and hypertension. We report on a consanguineous Arab
      family, in which two sibs inherited both CF and AME. Gene testing for AME
      revealed previously unreported mutation in the 11betaHSD2 gene. This report draws
      attention to the importance of recognizing the possibility of two recessive
      disorders in the same child in complex consanguineous families. Moreover, it
      provides a unique opportunity to highlight the implications of the coexistence of
      two genetic disorders on patient care and genetic counseling of the family. 

PMID- 25593613
TI  - Neutrophil/lymphocyte ratio, a possible diagnostic marker in clinical practice.

PMID- 25593614
TI  - Author reply to the editor.

PMID- 25593615
TI  - Cigarette price and smoking.

PMID- 25593616
TI  - Achieving HIV risk reduction through HealthMpowerment.org, a user-driven eHealth
      intervention for young Black men who have sex with men and transgender women who
      have sex with men.
AB  - Young, Black men who have sex with men and transgender women who have sex with
      men (YBMSM/TW) are at disproportionate risk for HIV and other sexually
      transmitted infections (HIV/STI). HealthMpowerment.org (HMP) is a mobile phone
      optimised online intervention that utilises behaviour change and gaming theories
      to reduce risky sexual behaviours and build community among HIV-positive and
      negative YBMSM/TW. The intervention is user-driven, provides social support, and
      utilises a point reward system. A four-week pilot trial was conducted with a
      diverse group of 15 YBMSM/TW. During exit interviews, participants described how
      HMP components led to behaviour changes such as asking partners' sexual history,
      increased condom use, and HIV/STI testing. The user-driven structure,
      interactivity, and rewards appeared to facilitate sustained user engagement and
      the mobile platform provided relevant information in real-time. Participants
      described the reward elements of exceeding their previous scores and earning
      points toward prizes as highly motivating. HMP showed promise for being able to
      deliver a sufficient intervention dose and we found a trend toward higher dose
      received and more advanced stages of behaviour change. In this pilot trial, HMP
      was well accepted and demonstrates promise for translating virtual intervention
      engagement into actual behaviour change to reduce HIV risk behaviours.

PMID- 25593619
TI  - A prospective evaluation of the contribution of ambient temperatures and
      transport times on infrared thermometry readings of intravenous fluids utilized
      in EMS patients.
AB  - BACKGROUND: During cold weather months in much of the country, the temperatures
      in which prehospital care is delivered creates the potential for inadvertently
      cool intravenous fluids to be administered to patients during their transport and
      care by emergency medical services (EMS). There is some potential for patient
      harm from unintentional infusion of cool intravenous fluids. Prehospital
      providers in these cold weather environments are likely using fluids that are
      well below room temperature when prehospital intravenous fluid (IVF) warming
      techniques are not being employed. It was hypothesized that cold ambient
      temperatures during winter months in the study location would lead to the
      inadvertent infusion of cold intravenous fluids during prehospital patient care.
      METHODS: Trained student research assistants obtained three sequential
      temperature measurements using an infrared thermometer in a convenience sample of
      intravenous fluid bags connected to patients arriving via EMS during two
      consecutive winter seasons (2011 to 2013) at our receiving hospital in Syracuse,
      New York. Intravenous fluids contained in anything other than a standard
      polyvinyl chloride bag were not measured and were not included in the study.
      Outdoor temperature was collected by referencing National Weather Service online
      data at the time of arrival. Official transport times from the scene to the
      emergency department (ED) and other demographic data was collected from the EMS
      provider or their patient care record at the time of EMS interaction. RESULTS:
      Twenty-three intravenous fluid bag temperatures were collected and analyzed.
      Outdoor temperature was significantly related to the temperature of the
      intravenous fluid being administered, b = 0.69, t(21) = 4.3, p < 0.001. Transport
      time did not predict the measured intravenous fluid temperatures, b = 0.12, t(20)
      = 0.55, p < 0.6. CONCLUSIONS: Use of unwarmed intravenous fluid in the
      prehospital environment during times of cold ambient temperatures can lead to the
      infusion of cool intravenous fluid and may result in harm to patients. Short
      transport times do not limit this risk. Emergency departments should not rely on
      EMS agencies' use of intravenous fluid warming techniques and should consider
      replacing EMS intravenous fluids upon ED arrival to ensure patient safety.

PMID- 25593618
TI  - Endotracheal intubation with a video-assisted semi-rigid fiberoptic stylet by
      prehospital providers.
AB  - BACKGROUND: Emergency medical technicians intubate patients in unfamiliar
      surroundings and with less than ideal positioning. This study was designed to
      evaluate advanced life support (ALS) emergency medical technicians' (EMTs)
      ability to successfully intubate a simulated airway using a video-assisted semi
      rigid fiberoptic stylet, the Clarus Video System (CVS). METHODS: ALS EMTs were
      first shown a brief slideshow and three example videos and then given 20 min to
      practice intubating a mannequin using both the CVS and standard direct
      laryngoscopy (DL). The mannequin was then placed on the floor to simulate field
      intubation at the scene. Each participant was given up to three timed attempts
      with each technique. Endotracheal tube position was confirmed with visualization
      by one of the study authors. Comparisons and statistical analysis were conducted
      using SPSS(r) Statistics 21 (IBM(r)). Demographics and survey results were also
      collected and analyzed. RESULTS: The median total time for intubation was 15.00 s
      for DL and 15.50 s for CVS revealing no significant difference between the two
      techniques (p = 0.425), and there was no significant difference in the number of
      attempts required to successfully place the endotracheal tube (ETT) (p = 0.997).
      Demographic factors including handedness and eye dominance did not seem to affect
      outcomes. Participants reported a relatively high level of satisfaction with the
      CVS. CONCLUSIONS: ALS EMTs were able to obtain intubation results similar to
      those of their usual direct laryngoscopy technique when utilizing a video
      assisted semi-rigid fiberoptic stylet with very limited instruction and
      experience with the device. The CVS technique warrants further study for use as
      an alternative to DL and video laryngoscopy in the prehospital difficult airway
      scenario.

PMID- 25593620
TI  - One-year overview of deep vein thrombosis prevalence in the ishinomaki area since
      the great East Japan earthquake.
AB  - After the Great East-Japan Earthquake, the prevalence of deep vein thrombosis
      (DVT) in disaster shelters in Ishinomaki (Pacific coast, Miyagi, Japan) was found
      much higher than that ever reported in Japan. In Ishinomaki, twelve patients were
      found to have pulmonary thromboembolism for one month since the earthquake and
      DVT was found in 10 of those patients. The calf DVT was examined using
      ultrasonography in the shelters (from March to July 2011) and in temporary
      emergency housings (from August to December 2011). Calf DVT was found in 190 of
      701 evacuees. DVT prevalence was higher in the tsunami-flooded shelters (34.2%)
      than in that in the non-flooded shelters (19.1%). This indicated that
      deteriorated and crowded condition in the tsunami-flooded shelters might induce
      thrombogenesis in calf veins. Therefore, evacuees were recommended to leave
      tsunami-flooded areas. DVT prevalence in the shelters was gradually reduced,
      however, that was still higher in the temporary emergency housings (8.9%) than in
      the non-disaster area in Japan (2.2% in Yokohama city). The risk of calf DVT in
      the temporary emergency housings was increased because of reduced blood flow in
      the calf veins caused by immobility. The residents of the housings were required
      to be physically active to avoid calf DVT. (English translation of Jpn J Phlebol
      2013; 24: 380-384). 

PMID- 25593617
TI  - Isolated middle cerebral artery dissection: a systematic review.
AB  - Acute stroke can be missed in the emergency department, particularly in younger
      patients and in those with more vague symptoms such as headache or dizziness.
      Cervicocephalic dissections are one group of etiologies for acute stroke in the
      young. While cervicocephalic dissections are not uncommon in clinical practice,
      isolated middle cerebral artery dissection (MCAD) has been rarely reported as a
      cause for stroke. We sought to review the clinical implications and
      pathophysiology of an isolated MCAD. We searched the medical literature for
      isolated MCAD in clinical stroke patients using MEDLINE, HighWire, and Google
      Scholar databases from 1966 to 2013 using the keywords 'middle cerebral artery
      dissection,' 'intracerebral artery dissection,' and 'middle cerebral artery
      dissection stroke.' We reviewed cases to learn various characteristics of
      isolated MCAD. A total of 61 cases (62.3% male, mean age 44.16 +/- 19.17 years)
      were reviewed from 54 publications. Most cases were reported from Asian countries
      (78.7%). Ischemic strokes were more common than hemorrhagic strokes (68.9%).
      Digital subtraction angiography was the most common imaging modality used to
      diagnose isolated MCAD (75.4%). Surgery was the preferred form of therapeutic
      intervention (39.3%). Males (n = 27/48, p = 0.0008) and those who presented with
      only ischemic syndromes (n = 22/48, p = 0.0009) had significantly higher rates of
      favorable outcome. Isolated MCAD is a rare disease that can contribute to the
      stroke burden of young patients. Further studies are needed to better
      characterize optimal treatment strategies and define outcomes for this rare
      condition. 

PMID- 25593621
TI  - Ultrasonographic findings and the clinical results of treatment for lymphedema.
AB  - We undertook this study using ultrasonography to examine structural changes
      occurring in the subcutaneous tissue with lymphedema. Ultrasonographic images
      were taken in 178 outpatients and 29 inpatients, with the images of the subcutis
      fluid accumulation, which was categorized into three types ( grade 0: absent,
      grade 1: a minimal amount of water, grade 2: stone-paved image due to excess
      water). Initial percentage of excess volume was correlated with the tissue fluid
      (grade 0: 7.5%, grade 1: 17.1%, grade 2: 30.5%, p <0.01). The higher the grade of
      fluid accumulation, the more important was the absolute reduction of lymphedema
      volume (grade 0: 2.5%, grade 1: 14.8%, grade 2: 33.2%, p <0.01). The percentage
      of severe lymphedema (stage2b + 3) was higher in inpatients than
      outpatients(89.3% vs. 45.8%), however, a significant decrease in the percentage
      of volume reduction was found for inpatients (29.4 +/- 15.1% vs. 15.4 +/- 14.2%,
      p <0.01). Echographic images can help to determine whether compression therapy
      will reduce lymphedema and to evaluate the treatment results by measuring tissue
      fluid. For severe lymphedema, a compression bandage was more effective than an
      elastic stocking. (English translation of Jpn J Phlebol 2013; 24: 287-294). 

PMID- 25593623
TI  - Long-term results of endovascular repair for distal arch and descending thoracic
      aortic aneurysms treated by custom-made endografts: usefulness of fenestrated
      endografts.
AB  - OBJECTIVE: We evaluated early and long-term results of atherosclerotic aneurysm
      repair with custom-made endografts. MATERIALS AND METHODS: Eighty-one consecutive
      patients underwent thoracic endovascular aortic repair with custom-made
      endografts. Fenestrated grafts were used in 37 patients (45.7%) to maintain blood
      flow of the neck and a landing zone for as long as possible for distal arch or
      proximal descending aneurysms. The rates of perioperative mortality, stroke,
      paraplegia, and primary endoleaks were assessed to evaluate in-hospital safety.
      The rates of endoleak development, survival, and freedom from aortic-related
      death were assessed to evaluate long-term efficiency. RESULTS: Twenty-four
      patients (29.6%) underwent urgent operations, and 38 (46.9%) underwent distal
      arch or proximal descending aortic aneurysm repair. There was one case (1.2%) of
      in-hospital mortality and no cases of stroke. Permanent spinal injury occurred in
      one patient (1.2%). Early and late endoleaks occurred in one and 16 patients,
      respectively. The actuarial survival rates were 88.9%, 64.9%, and 51.7% at 1, 5,
      and 10 years, respectively. The actuarial rates of freedom from endoleaks were
      90.1%, 81.3%, and 68.6% at 1, 5, and 10 years, respectively. CONCLUSION: Early
      results of custom-made endografts were excellent, and fenestrated endografts were
      safe for distal arch and proximal descending aortic aneurysms.

PMID- 25593622
TI  - Quantification of superficial venous reflux by duplex ultrasound-role of reflux
      velocity in the assessment the clinical stage of chronic venous insufficiency.
AB  - OBJECTIVES: This study we compare the duplex-derived parameters of reflux in
      patients with early and advanced superficial venous insufficiency (SVI) to
      identify parameters reflecting this. METHODS: Two thousand and one hundred sixty
      limbs with primary reflux, categorized according to the CEAP (clinical,
      etiologic, anatomic and pathophysiologic) classification, and the patients were
      divided into two groups (group I [C1-3, Ep, As, Pr]; group II [C4-6, Ep, As, Pr])
      were studied. The vein diameter, reflux duration(s), mean reflux velocity (MRV;
      cm/s), peak reflux velocity (PRV; cm/s), and total reflux volume (TRV; ml/s) were
      determined at the sapheno-femoral junction (SFJ), great saphenous vein (GSV) and
      sapheno-popliteal junction (SPJ). RESULTS: Age and the proportion of males were
      greater in group II. MRV, PRV and TRV were greater in group II at the SFJ, SPJ
      and in GSV (p <0.01 for all), although the duration of SPJ reflux was non
      discriminatory (p = 0.78). From receiver operating characteristic (ROC) curve,
      optimal cut-off points of 27.8, 47.8, and 36.2 cm/s for the PRV at the SFJ (p
      <0.01), GSV (p <0.01), and SPJ (p <0.01) discriminated between the two groups.
      CONCLUSION: PRV and MRV improved discrimination between early and advanced SVI
      compared to reflux duration.

PMID- 25593624
TI  - Strain analysis of wall motion in abdominal aortic aneurysms.
AB  - OBJECTIVE: In this exploratory study, we used ultrasound speckle-tracking
      methods, originally used for analyzing cardiac wall motion, to evaluate aortic
      wall motion. MATERIALS AND METHODS: We compared 19 abdominal aortic aneurysm
      (AAA) patients with 10 healthy volunteers (diameter, 48 mm vs. 15 mm). Motion
      pictures of the axial view of the aneurysm using ultrasonography were analyzed.
      Circumferential strain and strain rate at 6 equally divided segments of the aorta
      were semiautomatically calculated. We termed 'peak' strain and strain rate as the
      maximum of strain and strain rate in a cardiac cycle for each segment. We also
      evaluated the coefficient of variation of peak strain rate for the six segments.
      RESULTS: In the aneurysm and control groups, the mean values of peak strain along
      the 6 segments were 1.5% +/- 0.6% vs. 4.7% +/- 1.6% (p <0.0001), respectively.
      The coefficient of variation of the peak strain rate was higher in the AAA group
      (0.74 +/- 0.20) than in the control group (0.56 +/- 0.12; p <0.05). CONCLUSIONS:
      Aortic wall compliance decreased in the more atherosclerotic AAA group. The
      higher relative dispersion of strain rates in the AAA group is indicative of the
      inhomogeneous movement of the aortic wall.

PMID- 25593625
TI  - MR Venography for the Assessment of Deep Vein Thrombosis in Lower Extremities
      with Varicose Veins.
AB  - OBJECTIVE: To assess the performance of magnetic resonance venography (MRV) for
      pelvis and deep vein thrombosis in the lower extremities before surgical
      interventions for varicose veins. MATERIALS AND METHODS: We enrolled 72 patients
      who underwent MRV and ultrasonography before stripping for varicose veins of
      lower extremities. All images of the deep venous systems were evaluated by time
      of-flight MRV. RESULTS: Forty-six patients (63.9%) of all were female. Mean age
      was 65.2 +/- 10.2 years (37-81 years). There were forty patients (55.6%) with
      varicose veins in both legs. Two deep vein thrombosis (2.8%) and three iliac vein
      thrombosis (4.2%) were diagnosed. All patients without deep vein thrombosis
      underwent the stripping of saphenous veins, and post-thrombotic change was
      avoided in all cases. CONCLUSION: MRV, without contrast medium, is considered
      clinically useful for the lower extremity venous system.

PMID- 25593626
TI  - Pulse wave velocity involving proximal portions of the aorta correlates with the
      degree of aortic dilatation at the sinuses of valsalva in ascending thoracic
      aortic aneurysms.
AB  - OBJECTIVE: To determine the relationship between arterial stiffness measured in
      different aortic segments and the presence and extent of ascending thoracic
      aortic aneurysm (ATAA). METHODS: Patients at a Thoracic Aortic Diseases clinic at
      a University teaching hospital were compared to patients attending a Cardiology
      outpatient Clinic at the same institution. A non-invasive measure of vascular
      stiffness was performed using pulse wave velocity (PWV) measurement of several
      vascular segments-carotid-femoral pulse wave velocity (cfPWV), heart-femoral
      pulse wave velocity (hfPWV) and brachial-ankle pulse wave velocity (baPWV).
      Aortic dimensions were measured on echocardiogram. RESULTS: Patients with ATAA (N
      = 32) were 66 years and the same age as those without ATAA (N = 46). There was no
      significant difference between those with or without aortic aneurysm with respect
      to cfPWV, hfPWV or baPWV. In ATAA, there was a significant (p <0.05) inverse
      correlation between aortic diameter at the sinuses of Valsalva and cfPWV, as well
      as hfPWV, but not with baPWV. This relationship was not evident in persons
      without ATAA. CONCLUSION: Reduced aortic stiffness (increased compliance),
      assessed by cfPWV or hfPWV, correlates with larger aortic size of ATAA at the
      level of the sinuses of Valsalva but not at the ascending aorta, suggesting cfPWV
      may be a useful method to assess the size of ATAA at the level of the sinuses of
      Valsalva. Overall aortic stiffness assessed by PWV did not differentiate persons
      with or without an ATAA, in individuals who do not have a genetic or inheritable
      cause of their ATAA.

PMID- 25593627
TI  - Successful endovascular treatment of traumatic thoracic aortic injury complicated
      by severe pelvic hemorrhage.
AB  - A 25-year-old woman committed suicide with a high-rise fall and presented
      hypovolemic shock caused by blunt thoracic, abdominal injury. Enhanced computed
      tomography scan showed the pelvic hemorrhage and the transection of the
      descending thoracic aorta. After urgent transcatheter arterial embolization to
      stabilize bleeding from pelvic fracture, the thoracic aortic injury was treated
      with endovascular aortic repair using a GORE TAG endograft. She recovered from
      her injuries, and there was no evidence of endoleak in the follow-up computed
      tomography scan. In the treatment of traumatic aortic injury with associated
      severe injuries, the management of bleeding from associated injuries is
      important. 

PMID- 25593628
TI  - Penetration of an inferior vena cava filter into the aorta.
AB  - Transvenous placement of inferior vena cava (IVC) filters is commonly performed
      in selected patients with deep venous thrombosis and pulmonary embolism. However,
      filter placement is sometimes associated with serious complications. A common
      complication is asymptomatic perforation of the IVC and penetration of adjacent
      organs by the filter. Here, we report a case of an 83-year-old man whose
      prophylactic IVC filter penetrated the aorta. The patient was closely followed
      without surgical intervention for more than a year, and no additional
      complications were observed. 

PMID- 25593629
TI  - A Case of Adventitial Cystic Disease of the Popliteal Artery Progressing Rapidly
      after Percutaneous Ultrasound-guided Aspiration.
AB  - Adventitial cystic disease is a rare non-atherosclerotic vascular disease. We
      report a 36-year-old man with right intermittent claudication by adventitial
      cystic disease. computed tomography (CT) and magnetic resonance imaging (MRI)
      revealed an ovoid cystic mass compressing the right popliteal artery and causing
      severe stenosis of the lumen. Percutaneous aspiration was performed, which
      improved his symptoms. However, he complained of identical intermittent
      claudication two weeks later. Radiographic findings revealed that the cystic
      lesion had progressed rapidly. The cystic lesion was resected and the affected
      arterial segment was interposed. We consider that conventional surgical
      intervention remains the favored treatment option in the management of
      adventitial cystic disease. 

PMID- 25593630
TI  - Tracheo-Bronchial Obstruction and Esophageal Perforation after TEVAR for Thoracic
      Aortic Rupture.
AB  - A 67-year-old man was referred to our hospital for an ascending aortic aneurysm,
      thoracoabdominal aortic aneurysm and aortic regurgitation. Graft repair of the
      thoracic aortic arch and aortic valve replacement was given priority and
      completed, however he developed descending aortic rupture before the second
      scheduled surgery, and endovascular stent grafting was performed. He subsequently
      developed tracheobronchial obstruction and esophageal perforation. The patient
      underwent urgent esophagectomy and enterostomy with continuity later
      reestablished. However, he died of sepsis 5 months after surgery. Despite the
      less invasive nature of endovascular treatment, esophageal perforation can
      nevertheless occur and postoperative vigilance is well warranted. 

PMID- 25593631
TI  - Contrast Free Duplex-Assisted EVAR in Patients with Chronic Renal Insufficiency.
AB  - Renal insufficiency and allergy for iodinated contrast are the main contra
      indications for Endovascular Aortic Repair (EVAR). Various techniques have been
      used to minimize utilization of contrast in order to prevent contrast induced
      nephropathy. EVAR can be performed without nephrotoxic contrast, using additional
      duplex-guidance. This report describes three cases of duplex-assisted EVAR in
      patients with chronic renal insufficiency. 

PMID- 25593632
TI  - Spontaneous intercostal arterial rupture restrained by conservative management.
AB  - A spontaneous intercostal arterial rupture in patients without associated illness
      or trauma is extremely rare. We present a 58-year-old man with an idiopathic and
      spontaneous arterial rupture restrained by conservative management. He was
      admitted to our institute with an intermittent back pain lasting for 3 days. His
      past history included no notable diseases and chest trauma. An enhanced computed
      tomography revealed an effusion of blood around the descending aorta and hematoma
      from right 10th intercostal artery. Management of blood pressure and
      administration of tranexamic acid were performed and he was uneventfully
      discharged at 11 days after onset. 

PMID- 25593633
TI  - An easy and useful exposure technique using a malleable u-shaped retractor for
      proximal anastomosis in abdominal aortic replacement.
AB  - During surgery for an abdominal aortic aneurysm, various problems can occur at
      the proximal anastomosis. Adequate exposure must be secured, and the proximal
      anastomosis must be sutured firmly. We have used a malleable U-shaped retractor
      to easily secure exposure of the proximal anastomosis. Despite recent advances in
      endovascular treatment, abdominal aortic aneurysm repair often requires open
      surgery. We describe our malleable U-shaped retractor technique, which is very
      easy and facilitates the creation of a secure proximal anastomosis. 

PMID- 25593634
TI  - Case Report of Fire Eater's Pneumonia in Adolescent Female Patient - Evolution of
      Radiologic Findings.
AB  - BACKGROUND: We present a case of a 16-year-old girl with fire-eater's pneumonia
      (hydrocarbon pneumonitis). The goal of this report was to assess evolution of
      radiological findings. CASE REPORT: The reported case was unique because that was
      the first completely described case of fire-eater's pneumonia reported in an
      under-aged person. Moreover, this disease is very rare even in adults and only a
      few scientific reports can be found, mostly because of a small occupational
      group. CONCLUSIONS: The aim of this report was to show that the problem of fire
      eater's pneumonia can occur in under-aged patients and should be taken into
      consideration in case of severe pneumonia. Another objective was to point out
      that chest radiograph is not sufficient to depict the evolution of radiological
      manifestations.

PMID- 25593635
TI  - Correlative Imaging in a Patient with Cystic Thymoma: CT, MR and PET/CT
      Comparison.
AB  - BACKGROUND: Cystic thymoma is a rare variant of thymic neoplasm characterized by
      almost complete cystic degeneration with mixed internal structure. We describe a
      case of a 60 year-old woman with a cystic thymoma studied with advanced
      tomographic imaging stydies. CT, MRI and PET/CT with (18)F-FDG were performed;
      volumetric CT and MRI images provided better anatomic evaluation for pre
      operative assessment, while PET/CT was helpful for lesion characterization based
      on (18)F-FDG uptake. Although imaging studies are mandatory for pre-operative
      evaluation of cystic thymoma, final diagnosis still remains surgical. CASE
      REPORT: A 60-year-old woman with recent chest pain and no history of previous
      disease was admitted to our departement to investigate the result of a previous
      chest X-ray that showed bilateral mediastinal enlargement; for this purpose,
      enhanced chest CT scan was performed using a 64-rows scanner (Toshiba, Aquilion
      64, Japan) before and after intravenous bolus administration of iodinated non
      ionic contrast agent; CT images demonstrated the presence of a large mediastinal
      mass (11*8 cm) located in the anterior mediastinum who extended from the
      anonymous vein to the cardio-phrenic space, compressing the left atrium and
      causing medium lobe atelectasis; bilateral pleural effusion was also present.
      CONCLUSIONS: In conclusion, correlative imaging plays a foundamental role for the
      diagnostic evaluation of patient with cystic thymoma. In particular, volumetric
      CT and MRI studies can provide better anatomic informations regarding internal
      structure and local tumor spread for pre-operative assessment. Conversely,
      metabolic imaging using (18)F-FDG PET/CT is helpful for lesion characterization
      differentiating benign from malignant lesion on the basis of intense tracer
      uptake. The role of PET/MRI is still under investigation. However, final
      diagnosis still remains surgical even though imaging studies are mandatory for
      pre-operative patient management.

PMID- 25593636
TI  - Genome sequence of Coxiella burnetii strain Namibia.
AB  - We present the whole genome sequence and annotation of the Coxiella burnetii
      strain Namibia. This strain was isolated from an aborting goat in 1991 in
      Windhoek, Namibia. The plasmid type QpRS was confirmed in our work. Further
      genomic typing placed the strain into a unique genomic group. The genome sequence
      is 2,101,438 bp long and contains 1,979 protein-coding and 51 RNA genes,
      including one rRNA operon. To overcome the poor yield from cell culture systems,
      an additional DNA enrichment with whole genome amplification (WGA) methods was
      applied. We describe a bioinformatics pipeline for improved genome assembly
      including several filters with a special focus on WGA characteristics. 

PMID- 25593637
TI  - Promising pharmacological directions in the world of lysophosphatidic Acid
      signaling.
AB  - Lysophosphatidic acid (LPA) is a signaling lipid that binds to six known
      lysophosphatidic acid receptors (LPARs), named LPA1-LPA6. These receptors
      initiate signaling cascades relevant to development, maintenance, and healing
      processes throughout the body. The diversity and specificity of LPA signaling,
      especially in relation to cancer and autoimmune disorders, makes LPA receptor
      modulation an attractive target for drug development. Several LPAR-specific
      analogues and small molecules have been synthesized and are efficacious in
      attenuating pathology in disease models. To date, at least three compounds have
      passed phase I and phase II clinical trials for idiopathic pulmonary fibrosis and
      systemic sclerosis. This review focuses on the promising therapeutic directions
      emerging in LPA signaling toward ameliorating several diseases, including cancer,
      fibrosis, arthritis, hydrocephalus, and traumatic injury. 

PMID- 25593639
TI  - Thymosin Beta-4, Actin-Sequestering Protein Regulates Vascular Endothelial Growth
      Factor Expression via Hypoxia-Inducible Nitric Oxide Production in HeLa Cervical
      Cancer Cells.
AB  - Vascular endothelial growth factor (VEGF) is an important regulator of
      neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression
      of VEGF and thymosin beta-4 (Tbeta4), actin sequestering protein. Here, we
      investigated whether NO-mediated VEGF expression could be regulated by Tbeta4
      expression in HeLa cervical cancer cells. Hypoxia inducible NO production and
      VEGF expression were reduced by small interference (si) RNA of Tbeta4. Hypoxia
      response element (HRE)-luciferase activity and VEGF expression were increased by
      the treatment with N-(beta-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L
      penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition
      of Tbeta4 expression with Tbeta4-siRNA. In hypoxic condition, HRE-luciferase
      activity and VEGF expression were inhibited by the treatment with N(G)-monomethyl
      L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is
      accompanied with a decrease in Tbeta4 expression. VEGF expression inhibited by L
      NMMA treatment was restored by the transfection with pCMV-Tbeta4 plasmids for
      Tbeta4 overexpression. Taken together, these results suggest that Tbeta4 could be
      a regulator for the expression of VEGF via the maintenance of NOS activity. 

PMID- 25593640
TI  - Atractylochromene Is a Repressor of Wnt/beta-Catenin Signaling in Colon Cancer
      Cells.
AB  - Wnt/beta-catenin signaling pathway was mutated in about 90% of the sporadic and
      hereditary colorectal cancers. The abnormally activated beta-catenin increases
      the cancer cell proliferation, differentiation and metastasis through increasing
      the expression of its oncogenic target genes. In this study, we identified an
      inhibitor of beta-catenin dependent Wnt pathway from rhizomes of Atractylodes
      macrocephala Koidzumi (Compositae). The active compound was purified by activity
      guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2
      (4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed beta
      catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when
      they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3beta. AC
      down-regulated the nuclear level of beta-catenin through the suppression of
      galectin-3 mediated nuclear translocation of beta-catenin in SW-480 colon cancer
      cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken
      together, AC from A. macrocephala might be a potential chemotherapeutic agent for
      the prevention and treatment of human colon cancer. 

PMID- 25593638
TI  - Keratinocytic vascular endothelial growth factor as a novel biomarker for
      pathological skin condition.
AB  - Skin is an emerging target tissue in pharmaceutical and cosmetic science. Safety
      assessment for dermal toxicity is a critical step for development of topically
      applicable pharmaceutical agents and ingredients in cosmetics. Urgent needs exist
      to set up toxicity testing methods for dermal safety, and identification of novel
      biomarkers for pathological cutaneous alteration is highly required. Here we will
      discuss if vascular endothelial growth factor (VEGF) has a potential as a
      biomarker for dermal impairment. Experimental and clinical evidences for
      induction of keratinocytic VEGF under pathological conditions will be reviewed. 

PMID- 25593641
TI  - The Histone Deacetylase Inhibitor Trichostatin A Sensitizes Human Renal Carcinoma
      Cells to TRAIL-Induced Apoptosis through Down-Regulation of c-FLIPL.
AB  - Histone acetylation plays a critical role in the regulation of transcription by
      altering the structure of chromatin, and it may influence the resistance of some
      tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL) by regulating the gene expression of components of the TRAIL signaling
      pathway. In this study, we investigated the effects and molecular mechanisms of
      trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL
      induced apoptosis in Caki human renal carcinoma cells. Our results indicate that
      nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis
      compared with treatment with either agent alone. Cotreatment with TSA and TRAIL
      effectively induced cleavage of Bid and loss of mitochondrial membrane potential
      (MMP), which was associated with the activation of caspases (-3, -8, and -9) and
      degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the
      sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly
      reduced the levels of the cellular Fas-associated death domain (FADD)-like
      interleukin-1beta-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas
      those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic
      effect of TAS and TRAIL was perfectly attenuated in c-FLIPL-overexpressing Caki
      cells. Taken together, the present study demonstrates that down-regulation of c
      FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death
      receptor, as well as mitochondria-mediated apoptotic signaling pathways. 

PMID- 25593642
TI  - Tolfenamic Acid Suppresses Inflammatory Stimuli-Mediated Activation of NF-kappaB
      Signaling.
AB  - Tolfenamic acid (TA) is a traditional non-steroid anti-inflammatory drug (NSAID)
      and has been broadly used for the treatment of migraines. Nuclear factor kappa B
      (NF-kappaB) is a sequence-specific transcription factor and plays a key role in
      the development and progression of inflammation and cancer. We performed the
      current study to investigate the underlying mechanisms by which TA suppresses
      inflammation focusing on NF-kappaB pathway in TNF-alpha stimulated human normal
      and cancer cell lines and lipopolysaccharide (LPS)-stimulated mouse macrophages.
      Different types of human cells (HCT116, HT-29 and HEK293) and mouse macrophages
      (RAW264.7) were pre-treated with different concentrations of TA and then exposed
      to inflammatory stimuli such as TNF-alpha and LPS. Transcriptional activity of NF
      kappaB, IkappaB-alpha-degradation, p65 translocation and mitogen-activated
      protein kinase (MAPK) activations were measured using luciferase assay and
      Western blots. Pre-treatment of TA repressed TNF-alpha- or LPS-stimulated NF
      kappaB transactivation in a dose-dependent manner. TA treatment reduced
      degradation of IkappaB-alpha and subsequent translocation of p65 into nucleus. TA
      significantly down-regulated the phosphorylation of c-Jun N-terminal kinase
      (JNK). However, TA had no effect on NF-kappaB signaling and JNK phosphorylation
      in HT-29 human colorectal cancer cells. TA possesses anti-inflammatory activities
      through suppression of JNK/NF-kappaB pathway in different types of cells. 

PMID- 25593643
TI  - Therapeutic effects of s-petasin on disease models of asthma and peritonitis.
AB  - To explore the anti-allergic and anti-inflammatory effects of extracts of
      Petasites genus, we studied the effects of s-petasin, a major sesquiterpene from
      Petasites formosanus (a butterbur species) on asthma and peritonitis models. In
      an ovalbumin-induced mouse asthma model, s-petasin significantly inhibited the
      accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar
      fluids. S-petasin inhibited the antigen-induced degranulation of beta
      hexosamidase but did not inhibit intracellular Ca(2+) increase in RBL-2H3 mast
      cells. S-petasin inhibited the LPS induction of iNOS at the RNA and protein
      levels in mouse peritoneal macrophages. Furthermore, s-petasin inhibited the
      production of NO (the product of iNOS) in a concentration-dependent manner in the
      macrophages. Furthermore, in an LPS-induced mouse model of peritonitis, s-petasin
      significantly inhibited the accumulation of polymorpho nuclear and mononuclear
      leukocytes in peritoneal cavity. This study shows that s-petasin in Petasites
      genus has therapeutic effects on allergic and inflammatory diseases, such as,
      asthma and peritonitis through degranulation inhibition in mast cells,
      suppression of iNOS induction and production of NO in macrophages, and
      suppression of inflammatory cell accumulation. 

PMID- 25593644
TI  - Protective Effect of Liriodendrin Isolated from Kalopanax pictus against Gastric
      Injury.
AB  - In this study, we investigated the inhibitory activities on gastritis and gastric
      ulcer using liriodendrin which is a constituent isolated from Kalopanax pictus.
      To elucidate its abilities to prevent gastric injury, we measured the quantity of
      prostaglandin E2 (PGE2) as the protective factor, and we assessed inhibition of
      activities related to excessive gastric acid be notorious for aggressive factor
      and inhibition of Helicobacter pylori (H. pylori) colonization known as a cause
      of chronic gastritis, gastric ulcer, and gastric cancer. Liriodendrin exhibited
      higher PGE2 level than rebamipide used as a positive control group at the dose of
      500 MUM. It was also exhibited acid-neutralizing capacity (10.3%) and H(+)/K(+)
      ATPase inhibition of 42.6% (500 MUM). In pylorus-ligated rats, liriodendrin
      showed lower volume of gastric juice (4.38 +/- 2.14 ml), slightly higher pH (1.53
      +/- 0.41), and smaller total acid output (0.47 +/- 0.3 mEq/4 hrs) than the
      control group. Furthermore liriodendrin inhibited colonization of H. pylori
      effectively. In vivo test, liriodendrin significantly inhibited both of HCl/EtOH
      induced gastritis (46.9 %) and indomethacin-induced gastric ulcer (46.1%). From
      these results, we suggest that liriodendrin could be utilized for the treatment
      and/or protection of gastritis and gastric ulcer. 

PMID- 25593646
TI  - Ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, inhibits
      proliferation and differentiation of th17 cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a
      cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been
      associated with several autoimmune diseases, including experimental autoimmune
      encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced
      arthritis. In this study, we confirmed PPARgamma-mediated inhibition of Th17 cell
      differentiation and cytokine production at an early stage. Treatment with
      ciglitazone, a PPARgamma ligand, reduced both IL-1beta-mediated enhancement of
      Th17 differentiation and activation of Th17 cells after polarization. For Th17
      cell differentiation, we found that ciglitazone-treated cells had a relatively
      low proliferative activity and produced a lower amount of cytokines, regardless
      of the presence of IL-1beta. The inhibitory activity of ciglitazone might be due
      to decrease of CCNB1 expression, which regulates the cell cycle in T cells.
      Hence, we postulate that a pharmaceutical PPARgamma activator might be a potent
      candidate for treatment of Th17-mediated autoimmune disease patients. 

PMID- 25593645
TI  - Effect of Cordycepin-Enriched WIB801C from Cordyceps militaris Suppressing
      Fibrinogen Binding to Glycoprotein IIb/IIIa.
AB  - In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a
      n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet
      aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet
      aggregation, and had a synergistic effect together with cordycepin (W-cordycepin)
      from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE
      WIB801C and cordycepin stimulated the phosphorylation of VASP (Ser(157)) and the
      dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to
      glycoprotein IIb/IIIa (alphaIIb/beta3) and the release of ATP and serotonin in
      collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced
      CE-WIB801C-, and cordycepin-increased VASP (Ser(157)) phosphorylation, and
      increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to
      alphaIIb/beta3. Therefore, we demonstrate that CE-WIB801C-, and cordycepin
      inhibited fibrinogen binding to alphaIIb/beta3 are due to stimulation of cAMP
      dependent phosphorylation of VASP (Ser(157)), and inhibition of PI3K/Akt
      phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin
      may have preventive or therapeutic potential for platelet aggregation-mediated
      diseases, such as thrombosis, myocardial infarction, atherosclerosis, and
      ischemic cerebrovascular disease. 

PMID- 25593647
TI  - Genistein from Vigna angularis Extends Lifespan in Caenorhabditis elegans.
AB  - The seed of Vigna angularis has long been cultivated as a food or a folk medicine
      in East Asia. Genistein (4',5,7-trihydroxyisoflavone), a dietary phytoestrogen
      present in this plant, has been known to possess various biological properties.
      In this study, we investigated the possible lifespan-extending effects of
      genistein using Caenorhabditis elegans model system. We found that the lifespan
      of nematode was significantly prolonged in the presence of genistein under normal
      culture condition. In addition, genistein elevated the survival rate of nematode
      against stressful environment including heat and oxidative conditions. Further
      studies demonstrated that genistein-mediated increased stress tolerance of
      nematode could be attributed to enhanced expressions of stress resistance
      proteins such as superoxide dismutase (SOD-3) and heat shock protein (HSP-16.2).
      Moreover, we failed to find genistein-induced significant change in aging-related
      factors including reproduction, food intake, and growth, indicating genistein
      exerts longevity activity independent of affecting these factors. Genistein
      treatment also led to an up-regulation of locomotory ability of aged nematode,
      suggesting genistein affects healthspan as well as lifespan of nematode. Our
      results represent that genistein has beneficial effects on the lifespan of C.
      elegans under both of normal and stress condition via elevating expressions of
      stress resistance proteins. 

PMID- 25593648
TI  - 7alpha-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic
      Cells.
AB  - We investigated the question of whether 7-oxygenated cholesterol derivatives
      could affect inflammatory and/or immune responses in atherosclerosis by examining
      their effects on expression of IL-23 in monocytic cells. 7alpha
      Hydroxycholesterol (7alphaOHChol) induced transcription of the TLR6 gene and
      elevated the level of cell surface TLR6 protein in THP-1 monocytic cells.
      Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with
      7alphaOHChol resulted in enhanced production of IL-23 and transcription of genes
      encoding the IL-23 subunit alpha (p19) and the IL-12 subunit beta (p40). However,
      treatment with 7-ketocholesterol (7K) and 7beta-hydroxycholesterol (7betaOHChol)
      did not affect TLR6 expression, and addition of FSL-1 to cells treated with
      either 7K or 7betaOHChol did not influence transcription of the genes.
      Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated
      transcription of TLR6 induced by 7alphaOHChol as well as secretion of IL-23
      enhanced by 7alphaOHChol plus FSL-1. Inhibition of p38 MAPK or JNK resulted in
      attenuated secretion of IL-23. These results indicate that a certain type of 7
      oxygenated cholesterol like 7alphaOHChol can elicit TLR6-mediated expression of
      IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways. 

PMID- 25593649
TI  - Anti-Inflammatory Effects of Water Chestnut Extract on Cytokine Responses via
      Nuclear Factor-kappaB-signaling Pathway.
AB  - Water chestnut (Trapa japonica Flerov.) is an annual aquatic plant. In the
      present study, we showed that the treatment of water chestnut extracted with
      boiling water resulted in a significant increase 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical-scavenging activity and decrease the intracellular H2O2-induced
      accumulation of reactive oxygen species. In addition, water chestnut extract
      (WCE) inhibited lipopolysaccharide (LPS)-induced nitric oxide production and
      suppressed mRNA and protein expression of the inducible nitric oxide synthase
      gene. The cytokine array results showed that WCE inhibited inflammatory cytokine
      secretion. Also, WCE reduced tumor necrosis factor-alpha-and interleukin-6
      induced nuclear factor-alphaB activity. Furthermore, during sodium lauryl sulfate
      (SLS)-induced irritation of human skin, WCE reduced SLS-induced skin erythema and
      improved barrier regeneration. These results indicate that WCE may be a promising
      topical anti-inflammatory agent. 

PMID- 25593650
TI  - Spectrophotometric evaluation of dental bleaching under orthodontic bracket in
      enamel and dentin.
AB  - Aware of the diffusion capacity of bleaching in the dental tissues, many
      orthodontists are subjecting their patients to dental bleaching during
      orthodontic treatment for esthetic purposes or to anticipate the exchange of
      esthetic restorations after the orthodontic treatment. For this purpose specific
      products have been developed in pre-loaded whitening trays designed to fit over
      and around brackets and wires, with clinical efficacy proven. OBJECTIVE: The
      objective of this study was to evaluate, through spectrophotometric reflectance,
      the effectiveness of dental bleaching under orthodontic bracket. MATERIAL AND
      METHODS: Thirty-two bovine incisors crown blocks of 8 mm x 8 mm height lengths
      were used. Staining of tooth blocks with black tea was performed for six days.
      They were distributed randomly into 4 groups (1-home bleaching with bracket, 2-
      home bleaching without bracket, 3- office bleaching with bracket, 4 office
      bleaching without bracket). The color evaluation was performed (CIE L * a * b *)
      using color reflectance spectrophotometer. Metal brackets were bonded in groups 1
      and 3. The groups 1 and 2 samples were subjected to the carbamide peroxide at
      15%, 4 hours daily for 21 days. Groups 3 and 4 were subjected to 3 in-office
      bleaching treatment sessions, hydrogen peroxide 38%. After removal of the
      brackets, the second color evaluation was performed in tooth block, difference
      between the area under the bracket and around it, and after 7 days to verified
      color stability. Data analysis was performed using the paired t-test and two-way
      variance analysis and Tukey's. RESULTS: The home bleaching technique proved to be
      more effective compared to the office bleaching. There was a significant
      difference between the margin and center color values of the specimens that were
      subjected to bracket bonding. CONCLUSIONS: The bracket bond presence affected the
      effectiveness of both the home and office bleaching treatments. Key words:Tooth
      bleaching, spectrophotometry, orthodontics.

PMID- 25593651
TI  - An in vitro evaluation of the efficacy of a novel iontophoresis fluoride tray on
      remineralization.
AB  - OBJECTIVES: The aim of this study is to determine the effects on remineralization
      of a novel iontophoresis device called 'Fluorinex', conventional (acidulated
      phosphat fluoride) APF gel treatment, and conventional ionthophoresis device
      comparatively by laser fluorescence measurements. STUDY DESIGN: Artificial
      incipient carious lesions were created on immature, 60 intact premolar and molar
      teeth with no defects. The specimens were randomly allocated to four groups. In
      the first group 1.23% APF gel was applied to specimens by conventional method for
      4 minutes and in the second group 2% (sodium fluoride) NaF solution applied by
      conventional iontophoresis device for 4 minutes. In Fluorinex group specimens
      were pretreated with (copper chloride) CuCl2 for 1 minute and then treated for 4
      minutes with 1.23% APF gel in a Fluoritray. Control group was placed in distilled
      water for 4 minutes. After these applications all specimens were included to a pH
      cycling. DIAGNOdent pen measurement were obtained in three different time
      intervals; after incipient carious lesions, after fluoride treatments and after
      pH cycling. Specimens were studied by SEM(scanning electron microscopy) after
      artificial caries lesions and fluoride treatments. RESULTS: Alterations on
      DIAGNOdent pen measurements before and after treatment, the Fluorinex group was
      statistically different from conventional APF gel (p=0.011), conventional NaF
      iontophoresis (p<0.001) and control group (p<0.001). As the DIAGNOdent pen
      measurements before treatment and after pH cycling were compared, differences
      were statistically significant in Fluorinex and conventional APF gel groups
      (p<0.001). CONCLUSIONS: The results of this in vitro study has shown that
      fluoride application by Fluorinex was superior to the conventional APF gel
      application and NaF iontophoresis on incipient carious lesions. Key
      words:Fluoride, iontophoresis, remineralization.

PMID- 25593652
TI  - Can saliva offer an advantage in monitoring of diabetes mellitus? - A case
      control study.
AB  - OBJECTIVES: Diabetes Mellitus is emerging as a major health problem over these
      years. Present method of blood glucose monitoring by venepuncture is invasive
      leading to reduced patient compliance and thereby ineffective judicious
      monitoring. The need of the hour is to direct research in the direction of
      establishing painless and more acceptable blood glucose analysis method.The
      objective of the study is to conduct a comparative analysis of the concentrations
      of salivary glucose and blood glucose in type 2 diabetes mellitus patients. STUDY
      DESIGN: This study assessed glucose levels using the glucose oxidase method in
      blood and unstimulated saliva in 90 subjects who were divided into 3 equal groups
      of controlled type 2 diabetes, uncontrolled type 2 diabetes and those without
      diabetes. Statistical analysis was carried out using one way ANOVA, Post hoc
      Tukeys tests and Pearson's correlation coefficient test. RESULTS: Salivary
      glucose levels were significantly higher in patients with diabetes than controls.
      There was a significant positive correlation between salivary and plasma glucose
      levels in patients with diabetes. CONCLUSIONS: Glucose concentration in saliva is
      higher in diabetics but hyperglycemia does not influence salivary glucose levels.
      Further clarification is required to claim the diagnostic potentials of saliva in
      diabetes. Key words:Salivary glucose, type 2 diabetes mellitus, blood glucose.

PMID- 25593653
TI  - Clinical Evaluation of self and professionally applied desensitizing agents in
      relieving dentin hypersensitivity after a single topical application: A
      Randomized Controlled Trial.
AB  - OBJECTIVES: The objective of this study is to evaluate the efficacy of self and
      professionally applied desensitizing agents in relieving dentinal
      hypersensitivity after single direct topical application. STUDY DESIGN: This was
      a randomized controlled trial conducted among 57 patients. 8% Arginine paste was
      self-applied by the subject and Gluma desensitizer was applied by investigator.
      Numeric rating scale was used to measure hypersensitivity after tactile stimulus,
      Schiff scale was used for cold and air blast stimuli respectively. Scores were
      recorded at baseline, immediately, 15 and 30 days after the application.
      Friedman, Wilcoxon test as post hoc was used to analyze within group differences,
      between group differences analyzed using Mann Whitney U test (P<0.05 considered
      significant). RESULTS: 8% Arginine paste elicited significantly higher reductions
      in sensitivity (P<0.05) than that of Gluma group at all follow ups. There was a
      significant decrease in hypersensitivity for both the groups from baseline till
      final follow-up (P<0.05) for all three stimuli. 8% Arginine paste was found to be
      more effective than Gluma desensitizer in providing immediate relief from dentine
      hypersensitivity and also sustained the effect significantly for a period of 30
      days. CONCLUSIONS: Self applied 8% Arginine paste is effective than
      professionally applied Gluma desensitizer in relieving dentinal hypersensitivity
      immediately and over a period of one month. Key words:Dentine hypersensitivity,
      arginine, gluma, desensitizing agents.

PMID- 25593654
TI  - Impact of root canal preparation size and taper on coronal-apical micro-leakage
      using glucose penetration method.
AB  - OBJECTIVES: The purpose of this in vitro study was to assess the effect of root
      canal preparation size and taper on the amounts of glucose penetration. MATERIAL
      AND METHODS: For conducting this experimental study, eighty mandibular premolars
      with single straight canals were divided randomly into 2 experimental groups of
      30 samples each and 2 control groups. Using K-files and the balance force
      technique, canals in group 1 were prepared apically to size 25 and coronally to
      size 2 Peesoreamer. Group 2 were instrumented apically and coronally to size 40
      and size 6 Peesoreamer, respectively. Rotary instrumentation was accomplished in
      group 1; using size 25 and .04 tapered and in group 2, size 35 and .06 tapered
      Flex Master files. Canals were then obturated by lateral compaction of cold gutta
      percha. Glucose penetration through root canal fillings was measured at 1, 8, 15,
      22 and 30 days. Data were recorded as mmol/L and statistically analyzed with Mann
      Whitney U test (P value=. 05). RESULTS: In comparison to group 1, group 2 showed
      significant glucose leakage during the experimental period (P value < .0001).
      Also, in each experimental group, the amount of micro-leakage was significantly
      increased at the end of the study. CONCLUSIONS: Under the condition of this
      study, the amounts of micro-leakage through root canal fillings are directly
      related to the size and taper of root canal preparation and reducing the
      preparation size may lead to less micro-leakage. Key words:Dental leakage, root
      canal preparation, endodontics.

PMID- 25593655
TI  - Effect of root canal sealer and artificial accelerated aging on fibreglass post
      bond strength to intraradicular dentin.
AB  - OBJECTIVES: To evaluate the effect of root canal sealers (RCS) and specimen aging
      on the bond strength of fibre posts to bovine intraradicular dentin. MATERIAL AND
      METHODS: 80 teeth were used according the groups - Sealapextm, Sealer 26(r), AH
      Plus(r) and specimens aging - test with no aging and with aging. The canals
      prepared were filled using one of each RCS. The posts were cemented. Roots were
      cross-sectioned to obtain two slices of each third. Samples were submitted to
      push-out test. Failure mode was evaluated under a confocal microscope. The data
      were analysed by ANOVA, Tukey's, and Dunnet tests (alpha = 0.05). RESULTS: No
      significant difference was detected among RCS. Aged control presented higher bond
      strength than immediate control. The aging did not result significant difference.
      Adhesive cement-dentin failure was prevalent in all groups. CONCLUSIONS: RCS
      interfered negatively with bonding of fibreglass posts cemented with self
      adhesive resin cement to intraradicular dentin. Key words:Fibreglass post, bond
      strength, root dentin, endodontic sealer, aging.

PMID- 25593656
TI  - Root canal disinfection of immature dog teeth with apical periodontitis:
      Comparison of three different protocols.
AB  - OBJECTIVES: The present in vivo study was designed to assess the efficacy of 3
      root canal disinfection protocols in immature dog teeth with apical periodontitis
      (AP). MATERIAL AND METHODS: Forty immature premolars with pulp necrosis and AP of
      five Beagle dogs were used. Three experimental disinfection protocols were
      established. After irrigation with 40 ml 5.25% sodium hypochlorite using the
      Endovac system, in Group 1 canals were flushed with QMix solution; in Group 2,
      canals were flushed with QMix solution and 2% chlorhexidine gel dressing was
      placed for two weeks; and in Group 3, triantibiotic paste dressing was placed for
      two weeks. Canals were sampled after periapical lesions were radiographically
      visible (S1), after the first disinfection session (S2) and, in groups 2 and 3,
      after dressing (S3). RESULTS: After the first session of the disinfection
      protocol (S2), there was significant (p < 0.05) bacterial reduction in the three
      experimental groups. Microorganisms were absent in 100% of S2 samples in groups 1
      and 2, and in 75% of group 3 (p > 0.05). After dressing, 87.5% of the S3 samples
      showed increased bacterial count: in group 2, CFU counts (median = 891) were
      significantly higher than in group 3 (median = 18) (p = 0.03). CONCLUSIONS: In
      immature dog teeth with AP, root canal irrigation using QMix solution, with or
      without chlorhexidine gel dressing, or a triantibiotic paste dressing, provides
      the same level of disinfection than irrigation with 5.25% sodium hypochlorite
      alone in only one session. Key words:Apical periodontitis, chlorhexidine,
      Endovac, immature teeth, QMix solution, root canal disinfection, triantibiotic
      paste.

PMID- 25593657
TI  - Evaluation of treatment outcomes in a 3 years post-graduate orthodontic program
      using the peer assessment rating (par).
AB  - OBJECTIVES: To maintain high treatment quality it is important to evaluate
      orthodontic treatment results using objective methods. Outcome assessments allow
      private practitioners and university students to evaluate their results and raise
      the level of treatment outcomes. The aim of this study was to assess the
      orthodontic treatment outcome in a post-graduate orthodontics program in the
      University of Valencia (Spain) and to determine whether the treatment outcome is
      related to several factors as gender, age at start of the treatment, treatment
      duration, treatment method, extraction-non extraction treatment and cooperation
      needed. MATERIAL AND METHODS: A sample of 50 patients treated in the post
      graduate clinic was randomly selected. Pre-treatment and post-treatment study
      casts have been assessed by the Peer Assessment Rating (PAR index). The influence
      of various factors: gender, age at start of the treatment, treatment duration,
      treatment method, extraction-non extraction treatment, cooperation needed and
      number of students finishing each case, were statistically analyzed. RESULTS:
      According to the PAR index, orthodontic treatment reduced the malocclusion in a
      mean point reduction of 21.4 (CI 95% 18.7-24.1) and a mean percentage reduction
      of 80.5% (CI 95% 75.9-85.1). The total of the cases improved, 44% of the patients
      were in greatly improved category. CONCLUSIONS: None of the variables studied
      influenced significantly the treatment outcomes regarding the PAR. Based on the
      general classification criteria of the index, the results showed that the
      patients received a high standard treatment. Key words:Treatment outcome,
      orthodontics education, PAR Index.

PMID- 25593658
TI  - Eustachian tube dysfunction in OSMF- often present seldom discovered.
AB  - OBJECTIVES: To evaluate the effect of OSMF on the eustachian tube function and to
      correlate it with various grades of the disease. STUDY DESIGN: Twenty OSMF
      patients (40 ears) and 20 healthy controls (40 ears) were evaluated for
      eustachian tube function by eustachian tube function test, tympanometry and
      audiometry. RESULTS: The audiometric and tympanometric analysis showed no
      significant differences in hearing abilities of OSMF patients and controls and
      between various grades of OSMF, indicating no hearing impairment. However,
      eustachian tube function test revealed a statistically significant difference in
      eustachian tube function in OSMF patients and controls. Further, there was a
      significant increase in severity of dysfunction with increase in severity of
      disease. CONCLUSIONS: From the present study it is evident that the subjective
      function of Eustachian tube may be affected by disease process. But, probably the
      amount of deviation found in function of the eustachian tube is non contributing
      to cause a conductive hearing loss. Key words:Oral submucous fibrosis, eustachian
      tube function, tympanometry.

PMID- 25593659
TI  - Prevalence of lip lesions in an Indian population.
AB  - OBJECTIVES: Lip lesions are a frequent cause of consultation in dentistry, as
      they comprise a significant proportion of the oral lesions. The aim of the
      present study was to identify the different lip lesions and determine their
      prevalence in an Indian population. MATERIAL AND METHODS: 5231 patients visiting
      a Department of Oral Medicine and Radiology were examined for the presence of
      different lip lesions during the period from October, 2011 to May, 2013. The
      statistical analysis was done using Chi-square test and p<0.05 was considered to
      be statistically significant. RESULTS: The age of the patients ranged from 8-70
      years with a mean age of 32.6 years. The prevalence of lip lesions was 18.8%. The
      most commonly diagnosed lesions were those due to infections, which affected
      32.6% of the population, followed by mucocele (29.8%) and premalignant lesions
      and conditions which were observed in 20.6% of the population. Males were more
      commonly affected than females. CONCLUSIONS: The relatively high prevalence of
      the lip lesions suggests dental practitioners and health care workers to educate
      the patients and create more awareness regarding them. The dentists should have
      adequate knowledge about the etiology, clinical features, diagnosis and
      management of the lip lesions. Key words: Lip, lesions, India, prevalence.

PMID- 25593660
TI  - The effect of surface treatment with Er: YAG laser on shear bond strength of
      orthodontic brackets to fiber-reinforced composite.
AB  - OBJECTIVES: This study aimed to investigate the effect of surface treatment with
      Er:YAG laser on shear bond strength (SBS) of orthodontic brackets to fiber
      reinforced composite (FRC). STUDY DESIGN: Ninety human premolars were randomly
      divided into six groups of 15. FRC bars were bonded to the teeth with a flowable
      composite (FC) and then underwent following treatments. In group 1 no further
      treatment was performed. In group 2 the FRC surfaces were covered by FC. An
      Er:YAG laser was employed to treat FRCs in groups 3 ( 200 mJ/10 Hz) and 4 (300
      mJ/15 Hz). The FRC strips in groups 5 and 6 were first covered by FC and then
      irradiated with Er:YAG laser at 200 mJ/10 Hz (group 5) or 300 mJ/15 Hz (group 6).
      Stainless steel brackets were bonded to FRCs using a light-cure adhesive system.
      After 24 hours, the samples were tested for SBS and the adhesive remnant index
      (ARI) scores were determined. RESULTS: There was a significant difference in SBS
      among the study groups (P <0.001). Pairwise comparisons indicated that SBS was
      significantly lower in group 1 compared to all other groups (p<0.05) except group
      2. Bond strength in group 6 was significantly greater than all the study groups
      (p<0.05) except group 5. No significant difference was found in ARI scores among
      the groups. CONCLUSIONS: Covering the FRC surface by a layer of flowable
      composite and then application of Er:YAG laser at 300 mJ/15 Hz could be
      recommended to increase bond strength of orthodontic attachments to FRC. Key
      words:Fiber-reinforced composite, orthodontics, Sshear bond strength, laser,
      Er:YAG, surface treatment, bracket, FRC.

PMID- 25593661
TI  - Relationship between indication for tooth extraction and outcome of immediate
      implants: A retrospective study with 5 years of follow-up.
AB  - OBJECTIVES: The aims of this retrospective study were to evaluate the survival
      rate of a series of immediate implants after 3 years of follow-up and to study
      the relationship between survival and indication for tooth extraction. STUDY
      DESIGN: A retrospective study of patients treated with immediate implants between
      January 2003 and December 2008 was carried out. All patients receiving at least
      one post-extraction implant and a minimum follow-up of 5 years were included.
      RESULTS: After 60 months, 30 immediate implants had been lost in 17 patients,
      yielding a total implant success rate of 93.8%. None of the implants placed
      failed after the extraction of included canines (100% success rate). In 20 failed
      implants the reason for extraction had been severe periodontal disease (91.8%
      SR), in 4 endodontic failure (88.6%SR), in 3 unrestorable caries (95.9% SR), in 1
      untreatable fracture (95.2% SR) and in 2 improvement of prosthetic design (98.1%
      SR). No statistically significant influence was found between immediate implant
      failure and the reason for tooth extraction (p=0.11). CONCLUSIONS: The use of
      immediate implants is a successful alternative to replace missing teeth for
      severe periodontal disease, periapical pathology or by decay or untreatable
      fractures. Some reasons, such as periodontal disease itself is associated with a
      success rate significantly below the overall average. Similarly, the prosthetic
      design is associated with a better prognosis than all other reasons. Key
      words:Tooth extraction, immediate implants, success rate.

PMID- 25593662
TI  - Impact of fixed orthodontic appliances on quality of life among adolescents' in
      India.
AB  - CONTEXT: Malocclusion can seriously impair quality of life and they may affect
      various aspects of life, including function, appearance, interpersonal
      relationships and even career opportunities. OBJECTIVES: To assess and determine
      various factors that may influence the impact of orthodontic treatment on the
      quality of life of adolescents. STUDY DESIGN: Cross sectional study in
      adolescents of Moradabad was conducted on 109 males and 113 females (n=222)
      adolescents having a fixed orthodontic appliance, aged 13 to 22 years (mean
      17.5+/-1.5). A pre-structured questionnaire designed by Mandall et al, with nine
      conceptual impact sub-scales to highlight the problem faced by the patient in
      daily life after wearing the appliance was used to collect the data. Unpaired t
      test was used to determine the statistical significance and the influence of
      variables were analysed using multiple linear regression analysis. RESULTS:
      Factors which demonstrated high impact were oral hygiene (Mean=3.42; SD=0.78)
      followed by time constraints (Mean=3.23; SD=0.72) and physical impact (Mean=3.00;
      SD=0.61). Gender difference showed statistical significance in social impact
      (p=0.009), time constraints (p=0.001) and travel or cost implications (p=0.009).
      Internal reliability of the questionnaire ranged from low to good (Cronbach's
      alpha 0.29-0.81). Test-retest reliability ranged from an intra-class correlation
      coefficient 0.09-0.42. CONCLUSIONS: Patients who had been comprehensively
      informed about their treatment had greatest levels of satisfaction and compliance
      with treatment. Younger patients showed an earlier adaptation to treatment with
      fixed appliances which influenced the treatment to be started at the earliest
      possible age. Key words:Impact, malocclusion, quality of life.

PMID- 25593663
TI  - A new technique to determine vertical dimension of occlusion from anthropometric
      measurement of interpupillary distance.
AB  - BACKGROUND: A number of techniques are being practiced for the evaluation of VDO,
      but none of them is scientifically more accurate than other. Each method
      advocated has its own limitations. OBJECTIVES: The purpose of this study was to
      find correlation between vertical dimension of occlusion (VDO) and interpupillary
      distance (IPD). MATERIAL AND METHODS: A cross-sectional study was conducted on
      400 dentate subjects comprising of 200 males and 200 females. Anthropometric
      measurement of VDO was recorded clinically using modified digital vernier
      caliper. Also, a standardized digital photograph of face was generated from the
      frontal aspect using a digital camera for the measurement of IPD in millimeters.
      Correlation between VDO and IPD was studied using Spearman's coefficient. For the
      execution of regression command and preparation of prediction equations to
      estimate VDO, Statistical Package for Social Sciences (SPSS) Software Version
      11.5 was used. RESULTS: VDO and IPD was more in males compared to females. VDO
      was significantly and positively correlated with IPD only in males whereas
      females showed a weak correlation. Hence, regression equation was derived only
      for males. VDO estimation using regression equation for IPD had a standard error
      of +/- 3.94 in males. CONCLUSIONS: Since the variations between VDO and IPD are
      within the range of 2-4 mm, VDO prediction through this method is reliable and
      reproducible for male patients. Also, the method is simple, economic, and non
      invasive; hence it could be recommended for everyday practice to determine
      vertical dimension of occlusion in case of male patients. Key
      words:Anthropometry, interpupillary distance, jaw relation, vertical dimension of
      occlusion.

PMID- 25593664
TI  - Double talon cusps on supernumerary tooth fused to maxillary central incisor:
      Review of literature and report of case.
AB  - Human tooth development is a continuous process begin at the sixth weeks in utero
      and extends to about sixth months after birth for the primary dentition and from
      sixteenth week in utero to late adolescence for permanent dentition. There is no
      other organ of the human body which takes so long to attain its ultimate
      morphology as dentition. Several physiologic growth processes participate in the
      progressive development of the teeth including: initiation, proliferation,
      histodifferentiation, morphodifferentiation, apposition, calcification, and
      eruption. Aberrations in different stages of tooth development can result in
      unique manifestations both in primary and permanent dentitions. The fact that
      premaxilla is the predilection site for the occurrence of supernumerary teeth,
      talon cusp, dens invaginatus, and geminated teeth may suggest that the
      embryological development of premaxilla differ from other sites of the jaws. The
      dental abnormalities presented in this review are of great concern to dentist and
      parents because they create clinical, pathological and esthetic problems. Dental
      practitioner should be aware of the clinical sign, associated problems and
      treatment options for a given case. Key words:Double talon cusps, fusion,
      supernumerary, case report. 

PMID- 25593665
TI  - Mandibular talon cusps: A Systematic review and data analysis.
AB  - OBJECTIVES: The purpose of the present study was to evaluate mandibular talon
      cusps distribution from the comprehensive literature search and proposal of new
      classification Material and Methods: The study was a review of articles published
      in the English language from January 1960 to December 2013. The
      PubMed/MEDLINE/Google Scholor databases were searched electronically using 'talon
      cusp', 'dens evaginatus', 'anterior teeth', mandible, 'primary dentition' and '
      permanent dentition' as search terms in various combinations. The citation lists
      from the included references were subsequently examined, and a hand search was
      also performed in an attempt to identify additional reports. The distribution,
      characteristics, common tooth type, associated dental anomaly and proposal of new
      classification have been included in final data analysis. Descriptive statistics
      were carried out using Chi square test (SPSS, version 17). RESULTS: Overall 37
      citations were retrieved from the literature where one was prevalence studies and
      rest were case reports among those two were duplication. Total 35 articles with
      43 patients were reported on mandibular talon cusps. Males were predominantly
      affected than females (p<0.05). Eight cases (19%) were reported in archeological
      skulls 81% were clinical reports. Forty cases (93%) were reported in permanent
      dentition while 7% cases in primary dentition. Lingual mandibular talon are more
      common than facial type in permanent dentition facial talons (p<0.05). Seven
      cases (18%) were bilaterally involved. Double tooth (45%) was commonly associated
      with mandibular talons. Most of the cases reported from Asia and asia derived
      populations. CONCLUSIONS: Central incisor is the most common tooth type that
      effected by talon cusp in permanent dentition and lateral incisor is in primary
      dentition. Lingual talons are common in mandible. Double tooth common dental
      anomaly associated with mandibular talon cusp. Most of the case reported from
      Asia. Talon cusps should be classified as facial, lingual, and facial and lingual
      types. Key words:Double tooth, permanent dentition, primary dentition, mandibular
      arch, Talon cusp.

PMID- 25593667
TI  - Knowledge and awareness regarding biomedical waste management in dental teaching
      institutions in India- A systematic review.
AB  - OBJECTIVES: Proper handling, treatment and disposal of biomedical wastes are
      important elements in any health care setting. Not much attention has been paid
      to the management of Biomedical Waste (BMW) in recent years, in dental colleges
      and hospitals in India. The present systematic review was conducted to assess
      knowledge and awareness regarding BMW management among staff and students of
      dental teaching institutions in India. MATERIAL AND METHODS: A systematic review
      of relevant cross-sectional studies was conducted regarding BMW management in
      India in dental teaching institutions in India. Six studies were finally included
      in the present review after conducting both electronic and manual search like
      Pubmed, EMBASE etc. and after making necessary exclusions. Potential biases were
      addressed and relevant data was extracted by the concerned investigators.
      RESULTS: Six studies were finally included in the review. Colour coding of wastes
      was not done by 67% of the subjects in one of the studies conducted in Haryana.
      Almost all the subjects agreed to the fact that exposure to hazardous health care
      waste can result in disease or infection in another study. According to another
      study reports, none of the respondents was able to list the legislative act
      regarding BMW when asked. CONCLUSIONS: The results of the present review showed
      that knowledge and awareness level of subjects was inadequate and there is
      considerable variation in practice and management regarding BMW. There is a great
      need for continuing education and training programmes to be conducted in dental
      teaching institutions in India. Key words:Biomedical waste, knowledge, awareness,
      dentists, institution.

PMID- 25593666
TI  - Prevalence, etiology, diagnosis, treatment and complications of supernumerary
      teeth.
AB  - The aim of this article was to review the literature on supernumerary teeth,
      analyzing their prevalence, etiology, diagnosis, treatment and possible
      complications. An electronic search was made in the Pubmed-Medline database up to
      January 2014 using the key search terms "multiple supernumerary teeth" (n=279),
      "prevalence supernumerary teeth" (n=361), and "supernumerary teeth" (n=2412). In
      addition to the articles initially identified, others were included in the review
      proceeding from a manual search and from any references considered of relevance.
      Supernumerary teeth are those that exceed the normal dental formula. They are
      more common in men, more common in the upper maxilla, and more prevalent in
      permanent dentition. Complications associated with supernumerary teeth include
      dental impaction, delayed eruption, ectopic eruption, overcrowding, spacing
      anomalies and the formation of follicular cysts. The treatment of supernumerary
      teeth depends on their type, position, and possible complications, detected
      clinically and radiographically. No clear consensus exists as to the best time to
      extract unerupted supernumerary teeth. Key words:Hyperdoncia, supernumerary
      teeth, impacted teeth, treatment, permanent teeth, deciduous teeth. 

PMID- 25593668
TI  - Treatment of multiple traumatized anterior teeth associated with an alveolar bone
      fracture in a 20-year-old patient: A 3-year follow up.
AB  - Intrusive luxation is a type of recognizable luxation injury represented by a
      deeper axial displacement of the tooth toward the alveolar bone. Treatment
      strategies include waiting for the tooth to return to its position, immediate
      surgical repositioning, and repositioning through dental traction by orthodontic
      devices. The aim of this case report was to present the management of severe
      dental trauma and later restoration following IADT. A 20-year-old patient was
      presented after fainting at home four hours before, resulting in a dento-alveolar
      trauma. Clinical examinations revealed a traumatic intrusion, in 1.2, 1.1 and
      2.1, uncomplicated crown fractures in 1.1 and 2.1 and a complicated crown-root
      fracture in 2.2. The diagnosis was confirmed with CBCT. Following IADT protocol,
      the emergency treatment consisted of the surgical repositioning and semi-rigid
      splinting using orthodontic wire-composite, replacing the buccal bone plate, and
      postoperative instructions to the patient regarding oral hygiene. After 2 weeks
      the root canal treated and filled with fiberglass posts in 1.2, 1.1, 2.1 and 2.2.
      Splint was removed after 4 weeks and the IADT reassessment protocol followed,
      with revisions at 6-8 weeks, 6 months, a year and annual reviews for 5 years. A
      year after the treatment, the traumatized teeth were restored with minimally
      invasive preparations of feldspathic ceramic. Esthetics and function were
      recorded with a 3-year follow-up period. Key words:Intrusive luxation, dental
      trauma, crown-root fracture, dento-alveolar trauma, permanent tooth, CBCT. 

PMID- 25593669
TI  - Coexistence of two talon cusps and two dens invaginatus in a single tooth with
      associated radicular cyst-a case report and review of literature.
AB  - Talon cusp (TC) and dens invaginatus (DI) are relatively rare developmental
      anomalies which affect the shape of teeth. TC is an additional cusp that projects
      predominately from the lingual surface of anterior teeth. DI is a deep surface
      invagination of the crown or root which is commonly detected on routine
      radiographic examination. Both of these anomalies are observed more frequently in
      permanent maxillary lateral incisor. Isolated cases of single TC and DI are
      extensively reported in dental literature. Occasionally two talon cusps (TCs) in
      the same tooth as well as double and triple invaginations in one tooth are
      reported separately. Coexistence of these two anomalies in a single tooth is
      considered extremely rare, but still there are few reported cases. However,
      coexistence of two TCs and double DI in a single tooth is not reported till date.
      We hereby report the first case of coexistence of two TCs and double DI in a
      single tooth of a 23 year old female and use of platelet-rich fibrin (PRF) in the
      management of associated radicular cyst. Also, literature on coexistence of these
      two anomalies in a single tooth is reviewed. Key words:Coexistence, dens
      invaginatus, radicular cyst, talon cusp. 

PMID- 25593670
TI  - Synchronic nasopharyngeal and intraparotid warthin tumors: A case report and
      literature review.
AB  - Warthin tumor is the second most frequent benign salivary gland tumor after
      pleomorphic adenoma; it occurs almost exclusively in the parotid gland and peri
      parotideal lymph nodes, although it may rarely present in other locations. It may
      be multicentric and bilateral in a small percentage of cases. Nasopharyngeal
      Warthin tumor is very rare, and the presence of a synchronic WT involving
      nasopharynx and parotid is an exceptional event, as it has been described only
      twice in the literature. In this article we report an additional case of a
      synchronic Warthin tumor and review the related literature. Key words:Warthin
      tumor, synchronic WT, multicentrico, nasopharynx. 

PMID- 25593671
TI  - A rare occurrence of bilateral C-shaped roots in mandibular first and second
      premolars diagnosed with the aid of spiral computed tomography.
AB  - The C-shaped canal system is an anatomical variation mostly seen in mandibular
      second molars, although it can also occur in maxillary and other mandibular
      molars. Such variation in the root canal anatomy is uncommon in mandibular first
      premolars and very rare in mandibular second premolars. The C-shaped canal is so
      named for the cross-sectional morphology of the root and root canal. The main
      anatomic feature of C-shaped canals is the presence of a fin or web connecting
      the individual root canals. Failure of the Hertwig's epithelial root sheath to
      fuse on the lingual or buccal root surface is the main cause of C-shaped roots,
      which always contain a C-shaped canal. This case report describes an unusual
      occurrence of C-shaped roots in mandibular first and second premolars
      bilaterally, diagnosed with the aid of spiral computed tomography. Key
      words:Canal configuration, C-shape, mandibular first premolar, mandibular second
      premolar, spiral computed tomography scans. 

PMID- 25593672
TI  - Gossypiboma in the oral region: Case report and literature review.
AB  - Gossypiboma is an inflammatory reaction to a foreign body, specifically composed
      of a cotton matrix left behind after surgery. The present study aims to present a
      case report of gossypiboma 23 years after a dental surgery and to make a
      literature review of the English language cases published on the issue. A 42-year
      old woman was attended to evaluate complaints of pain on the right side of the
      maxilla. The patient reported that dental extractions in this region had been
      performed over a period of nearly 23 years. The panoramic radiograph demonstrated
      an opacity in the right maxillary sinus, which presented a spongiform aspect,
      irregularly shaped radiopaque image, as well as a rupture of the maxillary
      sinus's lower cortical layer. A surgical excision was performed, and the
      histopathological diagnosis was of gossypiboma. Six similar cases have also
      reported of gossypiboma in the oral region; however, calcification was only
      identified in the present case report. The patient is currently undergoing follow
      up and has presented no complaints of pain or recurrence. Key words:Gossypiboma,
      textiloma, muslinoma, gauzoma, oral region. 

PMID- 25593673
TI  - Invasive maxillary sinus aspergillosis: A case report successfully treated with
      voriconazole and surgical debridement.
AB  - INTRODUCTION: Invasive aspergillosis of the paranasal sinuses is a rare disease
      and often misdiagnosed; however, its incidence has seen substancial growth over
      the past 2 decades. Definitive diagnosis of these lesions is based on
      histological examination and fungal culture. CASE REPORT: An 81-year-old woman
      with a history of pain in the left maxillary region is presented. The diagnosis
      was invasive maxillary aspergillosis in immunocompetent patient, which was
      successfully treated with voriconazole and surgical debridement. Possible
      clinical manifestations, diagnostic imaging techniques and treatment used are
      discussed. Since the introduction of voriconazole, there have been several
      reports of patients with invasive aspergillosis who responded to treatment with
      this new antifungal agent. CONCLUSIONS: We report the importance of early
      diagnosis and selection of an appropriate antifungal agent to achieve a
      successful treatment. Key words:Invasive aspergillosis, voriconazole, fungal
      sinusitis, antifungal agent, open sinus surgery.

PMID- 25593674
TI  - Functional reconstruction after subtotal glossectomy in the surgical treatment of
      an uncommon and aggressive neoplasm in this location: Primary malignant melanoma
      in the base of the tongue.
AB  - Primary malignant melanoma of the oral cavity is a rare neoplasm, especially on
      the tongue. We report a case of mucosal melanoma at the base of the tongue, an
      extremely rare location (only about 30 cases have been reported in literature).
      The extension study doesn't revealed distant metastatic lesions. The patient was
      treated by subtotal glossectomy and bilateral functional neck dissection. Tongue
      is one of the most difficult structures to reconstruct, because of their central
      role in phonation, swallowing and airway protection. The defect was reconstructed
      with anterolateral thigh free flap. Surgical treatment was supplemented with
      adjuvant immunotherapy. The post-operative period was uneventful. At present, 24
      months after surgery, patient is asymptomatic, there isn't evidence of recurrence
      of melanoma and he hasn't any difficulty in swallowing or phonation. Key
      words:Malignant mucosal melanoma, anterolateral thigh free flap, phonation,
      swallowing. 

PMID- 25593675
TI  - Massive glosso-cervical arteriovenous malformation: The rationale for a
      challenging surgical resection.
AB  - Massive arterivenous malformations (AVM) in the cervico-facial area are rare but
      potentially life-threatening. Treatment protocols are not well-established. A 41
      year old man presented large painless rubber-like mass within the entire neck,
      which also extended intraorally through the floor of the mouth, showing a slow
      growing pattern for 5 years. Angiography diagnosed it as cervicofacial AVM.
      Treatment approach consisted on the embolization of the right upper thyroid,
      lingual and facial arteries under intravenous sedation. Three days later,
      bilateral radical neck dissection and subtotal glossectomy was performed. A
      musculo-cutaneous pectoralis major pedicled flap was harvested to reconstruct the
      floor of the mouth. Treatment of massive AVMs in the cervico-facial area is
      challenging due to the associated disfigurement and frequent recurrence rate due
      to incomplete resection. Also, massive bleeding may be present despite pre
      operative super-selective embolization. A new case is presented with focus on
      surgical treatment considerations. Key words:Arteriovenous malformation, high
      flow vascular malformation, cervical region, tongue, surgical resection. 

PMID- 25593676
TI  - Recognizing patterns of visual field loss using unsupervised machine learning.
AB  - Glaucoma is a potentially blinding optic neuropathy that results in a decrease in
      visual sensitivity. Visual field abnormalities (decreased visual sensitivity on
      psychophysical tests) are the primary means of glaucoma diagnosis. One form of
      visual field testing is Frequency Doubling Technology (FDT) that tests
      sensitivity at 52 points within the visual field. Like other psychophysical tests
      used in clinical practice, FDT results yield specific patterns of defect
      indicative of the disease. We used Gaussian Mixture Model with Expectation
      Maximization (GEM), (EM is used to estimate the model parameters) to
      automatically separate FDT data into clusters of normal and abnormal eyes.
      Principal component analysis (PCA) was used to decompose each cluster into
      different axes (patterns). FDT measurements were obtained from 1,190 eyes with
      normal FDT results and 786 eyes with abnormal (i.e., glaucomatous) FDT results,
      recruited from a university-based, longitudinal, multi-center, clinical study on
      glaucoma. The GEM input was the 52-point FDT threshold sensitivities for all
      eyes. The optimal GEM model separated the FDT fields into 3 clusters. Cluster 1
      contained 94% normal fields (94% specificity) and clusters 2 and 3 combined,
      contained 77% abnormal fields (77% sensitivity). For clusters 1, 2 and 3 the
      optimal number of PCA-identified axes were 2, 2 and 5, respectively. GEM with PCA
      successfully separated FDT fields from healthy and glaucoma eyes and identified
      familiar glaucomatous patterns of loss.

PMID- 25593677
TI  - Toxins and antimicrobial peptides: Interactions with membranes.
AB  - The innate immunity to pathogenic invasion of organisms in the plant and animal
      kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of
      defense. In addition to these natural peptide antibiotics, similar cationic
      peptides, such as the bee venom toxin melittin, act as nonspecific toxins.
      Molecular details of AMP and peptide toxin action are not known, but the
      universal function of these peptides to disrupt cell membranes of pathogenic
      bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is
      widely accepted. Here, we have utilized spectroscopic techniques to elucidate
      peptide-membrane interactions of alpha-helical human and mouse AMPs of the
      cathelicidin family as well as the peptide toxin melittin. The activity of these
      natural peptides and their engineered analogs was studied on eukaryotic and
      prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of
      anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide
      potency, was monitored with a sensitive fluorescence leakage assay. Detailed
      molecular information on peptide-membrane interactions and peptide structure was
      further gained through vibrational spectroscopy combined with circular dichroism.
      Finally, steady-state fluorescence experiments yielded insight into the local
      environment of native or engineered tryptophan residues in melittin and human
      cathelicidin embedded in bilayer vesicles. Collectively, our results provide
      clues to the functional structures of the engineered and toxic peptides and may
      impact the design of synthetic antibiotic peptides that can be used against the
      growing number of antibiotic-resistant pathogens.

PMID- 25593678
TI  - Unilateral orchidectomy in donkey (Equus asinus): Evaluation of different
      surgical techniques, histological and morphological changes on remaining testis.
AB  - Unilateral orchidectomy (UO) is required when further breeding potential is
      important. It is sometimes necessary to remove a single testis in a matured
      stallion for therapeutic reasons. In this study, twelve donkeys were used to
      evaluate three techniques of unilateral castration, histological and
      morphological changes on the remaining testis. Results of the study showed that
      each of the surgical techniques used had its advantages and disadvantages in
      comparison with the other two techniques. Therefore the selection among the three
      techniques depends on the surgeon preferences and the environment in which the
      unilateral orchidectomy is performed. The volume of the remaining testis recorded
      at the end of the study was significantly greater than that estimated at the
      start of the study (p < 0.05). The percentage of sperm motility obtained from the
      remaining testis was significantly decreased (p < 0.05). Histological examination
      of the testis in open surgery (group I) (where the scrotum was left opened)
      revealed severe hemorrhages, edema and fibrosis. The test is showed degenerative
      changes in the seminiferous tubules and interstitial orchitis. Histological
      examination of the testes removed using a closed technique, (in groups II and
      III) where the scrotum wound was sutured, revealed hyperplasia of spermatogenic
      series and Leydig cells. In conclusion, unilateral orchidectomy had compensatory
      effects on the weight and volume of remaining testis. Adverse effects on sperm
      motility and viability can affect the fertility of the animal. 

PMID- 25593679
TI  - The in vitro effect of leptin on semen quality of water buffalo (Bubalus bubalis)
      bulls.
AB  - The purpose of this study was to evaluate the probable effects of leptin addition
      in different levels to the semen extender on sperm quality (motility and motility
      parameters, viability, sperm membrane integrity, and DNA damage). Semen specimens
      were evaluated immediately after leptin addition, equilibration time and after
      thawing the frozen semen. Five healthy buffalo bulls (5 ejaculates from each
      bull) were used. Each ejaculate was diluted at 37 C with tris-based extender
      containing 0 (control), 10, 20, 50, 100, and 200 ng mL(-1) leptin. The diluted
      semen was kept 4 hr in refrigerator to reach to the equilibration time and then
      packed in 0.5 mL French straws and frozen in liquid nitrogen. Our results showed
      that, in the fresh semen, no significant difference was observed in all sperm
      quality parameters evaluated among all of the examined leptin concentrations.
      Addition of 10 ng mL(-1) leptin into semen extender significantly preserved sperm
      motility, all of the motility parameters, and viability in equilibrated semen
      compared to that of control group. However, in vitro addition of 200 ng mL(-1)
      leptin, significantly decreased theses parameters. In the frozen thawed semen,
      all leptin concentrations decreased sperm motility and viability, but significant
      decrease was observed in concentrations of 100 and 200 ng mL(-1). Adding leptin
      to semen extender did not have any significant influence on sperm DNA damage and
      sperm membrane integrity in all examined groups. These findings suggest that in
      vitro addition of 10 ng mL(-1) leptin could preserve sperm motility and viability
      in cooled semen of buffaloes. 

PMID- 25593680
TI  - Effects of different levels of vitamin premix in finisher diets on performance,
      immuno-competence and meat lipid oxidation of chickens fed on corn-soybean meal.
AB  - The present study was carried out to examine the effects of a vitamin premix (VP)
      reduction or withdrawal from finisher diet (29-43 days) on performance, immuno
      competence, and characteristics of leg bones and meat lipid oxidation of chickens
      fed on corn-soybean meal based diet. A total of 900 male broiler chickens (Ross
      308) were allocated to five treatment groups (0, 33%, 66%, 100% and 133% VP),
      with nine replicates per treatment group. At 29 and 36 days of ages, four birds
      from each replicate were injected with sheep red blood cells (SRBC). The cell
      mediated immunity was determined via phytohemagglutinin (PHA) and 1-chloro 2-4
      dinitrobenzen (DNCB) at 34 and 42 days of ages. At 33, 38 and 43 days of age, 42
      days of ages, and two birds of each replicate were slaughtered and bone
      parameters measured. The oxidative stability was evaluated by thiobarbituric acid
      reactive substances (TBARS) on the thigh samples that were stored for 90 day at 
      80 C. The results showed that reduction or withdrawal of VP from diets at
      different time points of the finisher period did not affect performance,
      immunocompetence and characteristics of leg bones. Results of TBARS showed that
      lipid peroxidation of the treatment without VP was significantly higher than of
      the other treatments when slaughtered at 43 days of age. Finally, the results of
      this study demonstrated that it is not possible to reduce the VP in finisher
      broilers' diets without negative effects on meat quality during the time of
      freezing. 

PMID- 25593681
TI  - The effects of vitamin B12 and diclofenac and their combination on cold and
      mechanical allodynia in a neuropathic pain model in rats.
AB  - The present study was performed to investigate the effects of long-term
      intraperitoneal (IP) injection of vitamin B12 and diclofenac in separate and
      combined treatments on cold and mechanical allodynia in a neuropathic pain model
      in rats. Neuropathic pain was induced by crush injury in right tibial nerve.
      Acetone spray and von Frey tests were used to obtain cold and mechanical
      allodynia responses, respectively, on day 11 after nerve crush. Normal saline,
      vitamin B12 and diclofenac were injected intraperitoneally for 10 consecutive
      days after surgery. Normal saline treated rats showed cold and mechanical
      allodynia responses after nerve crush. Vitamin B12 at doses of 50, 100 and 200 ug
      kg(-1) and diclofenac at a dose of 2 mg kg(-1) produced antiallodynic effects.
      Antiallodynic effects were not observed when subanalgesic doses of vitamin B12
      (25 ug kg(-1)) and diclofenac (0.25 mg kg(-1)) were used together. By increasing
      the dose of vitamin B12 to an effective dose (100 ug kg(-1)), antiallodynic
      effects were observed when compared with diclofenac (0.25 mg kg(-1)) alone. The
      results indicated that vitamin B12 and diclofenac produced neuropathic pain
      suppressing effects. Moreover, a potentiation effect was observed between vitamin
      B12 and diclofenac. 

PMID- 25593682
TI  - Classification and grading of canine malignant mammary tumors.
AB  - Histological grading is a good parameter to stratify tumors according to their
      biological aggressiveness. The Elston and Ellis grading method in humans,
      invasive ductal breast carcinomas and other invasive tumors are routinely used.
      The aims of this study were classification of mammary gland tumors and also
      application of a human grading method in canine mammary carcinoma. The samples
      included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and
      sarcomas (n = 5). The carcinomas were classified as simple carcinoma 56.8% (n =
      21), complex carcinoma 13.5% (n = 5), carcinoma arising from benign tumor 10.8%
      (n= 4) and special type of carcinoma 5.4% (n = 2). Out of 32 carcinomas studied,
      37.5% (n = 12) grade I, 46.9% (n = 15) grade II and 15.6% (n = 5) grade III. This
      study demonstrated that the Elston and Ellis method of histological grading in
      canine mammary tumor is a reliable prognostic factor which is correlated with
      histopathological classification. 

PMID- 25593683
TI  - Effects of in vitro copper sulphate supplementation on the ejaculated sperm
      characteristics in water buffaloes (Bubalus bubalis).
AB  - This study was carried out to investigate effects of copper sulphate (CuSO4)
      additive to semen extenders on sperm parameters: progressive motility, viability,
      membrane integrity and DNA damage, after semen dilution and cryopreservation.
      Semen samples of 5 buffalo bulls of 3-5 years old were collected at 5 different
      occasions during the autumn 2011. A total number of 25 samples were used in each
      examination. Sperm progressive motility and viability were measured at 0 (T0), 60
      (T1) and 120 (T2) min after diluting semen in tris-citric acid extender
      containing 0 (control), 0.004, 0.008, 0.016, 0.032 and 0.064 mg L(-1) CuSO4.
      Later, semen was diluted in a tris-citric acid-egg yolk-glycerol extender
      containing the same amounts of CuSO4, cooled to 4 C and kept refrigerated for 4
      hr to equilibrate, sperm progressive motility, viability, membrane integrity and
      DNA damage were estimated. Then, semen was packed in 0.5 mL French straws and
      frozen in liquid nitrogen. Later, the frozen semen was thawed in 37 C water bath
      for 30 sec, and the same parameters as well as total antioxidant capacity (TAC)
      of the frozen-thawed semen were estimated. The results showed that copper
      additive at the rate of 0.032 mg L(-1) gives a better protection of sperms
      through the process of dilution, equilibration and freeze-thawing than that in
      control and other Cu concentrations, while 0.064 mg L(-1) CuSO4 had deleterious
      effect on the sperm. 

PMID- 25593684
TI  - Follicle stimulating hormone increases spermatogonial stem cell colonization
      during in vitro co-culture.
AB  - The complex process of spermatogenesis is regulated by various factors. Studies
      on spermatogonial stem cells (SCCs) have provided very important tool to improve
      herd genetic and different field. 0.2 to 0.3 percent of total cells of
      seminiferous tubules is consist of spermatogonial stem cells. To investigate and
      biomanipulation of these cells, proliferation and viability rate of cells should
      be increased in vitro, at first. Follicle stimulating hormone (FSH) has been
      suggested to play a determinant role in the survival of germ cells in addition to
      increasing spermatogonial proliferation. In this study, the in vitro effects of
      FSH on spermatogonial cell colony formation were investigated. Sertoli and
      spermatogonial cells were isolated from 3-5 months old calves. The identity of
      the Sertoli cells and spermatogonial stem cells were confirmed through
      immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and
      spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU
      mL(-1) FSH, before colony assay. Results indicated that, FSH increased in vitro
      colonization of spermatogonial cells in comparison with control group. In
      conclusion, using FSH provided proper bovine spermatogonial stem cell culture
      medium for in vitro study of these cells. 

PMID- 25593685
TI  - Foll Detection of Toxoplasma gondii in sheep and goats blood samples by PCR-RFLP
      in Urmia.
AB  - Infection by the protozoan parasite Toxoplasma gondii, is widespread in humans
      and many other warm-blooded animals. More than half billion of world human
      population has serum antibodies to T. gondii and Sheep and goats are more widely
      infected with T. gondii. T. gondii infection can be diagnosed indirectly with
      serological methods and directly by polymerase chain reaction (PCR),
      hybridization, isolation and histology. A total number of 124 goats and 113 sheep
      blood samples were collected from Urmia region and PCR was used for detection of
      the pathogenic protozoan T. gondii using B1 gene. The targeted B1 gene is highly
      conserved in all T. gondii strains and is multiple copy genes whit in the T.
      gondii genome. The method used for the characterization of T. gondii strains
      implied digestion with AluI restriction enzyme of the fragments amplified. The
      results indicated three positive sheep (1.26%) with one RFLP patterns. The
      results indicated that the same strain of T. gondii has infected sheep in the
      region. 

PMID- 25593686
TI  - Study on effect of salinity level of water on electrocardiogram and some of blood
      serum minerals in grass carp, Ctenopharyngodon idella.
AB  - In this study the effects of salinity on the electrocardiogram and some of blood
      serum minerals in grass carp were investigated. For this purpose, grass carp were
      exposed to concentrations of 4, 8 and 12 g L(-1) salinities and electrocardiogram
      of all fish was recorded. Blood samples were also collected from all fish and
      serum minerals were measured. Our results indicated that mineral level in the
      studied groups was significantly different. The average of heart rate per minute
      in control group and 4, 8 and 12 g L(-1) were 10.15, 10.06, 12.17 and 7.79 beat
      per min, respectively. In 8 g L(-1) group only the average of QT and ST segment
      decreased significantly in comparison with the control group (p < 0.05). In 12 g
      L(-1) group the average of heart rate per minute decreased significantly in
      comparison with 8 g L(-1) group (p < 0.05) and no difference in the average of
      heart rate per minute was observed in all groups. The average of RR, PT and ST
      segment in the 12 g L(-1) group were significantly more than the other groups (p
      < 0.05). The results showed that water salinity level increased to concentrations
      above 8 g L(-1) can have significant effect on the electrocardiogram and mineral
      level of blood serum in grass carp. These changes are probably can be considered
      as one of the causes of impairment of health and death of this fish species in
      the salinities more than 8 g L(-1) due to ion imbalance and cardiovascular
      disorders. 

PMID- 25593687
TI  - Detection of torque teno virus (TTV) in domestic village chickens in Iran.
AB  - Torque teno virus (TTV) is prevalent worldwide and has been extensively studied
      in human and some wild and domestic animals. As the studies on TTV in chickens
      was rare and there was no information about the infection of domestic village
      chickens with TTV and also structural resemblance of this virus to chicken anemia
      virus, the frequency of the infection in domestic village chickens in different
      villages in Isfahan (Iran) was investigated. Sera were collected from 50
      chickens. Viral DNA was extracted and subjected to polymerase chain reaction
      (PCR) using the previously described T801 and T935 primers that were used for
      amplification of a highly conserved non-coding region (UTR) of the viral genome
      in a single round of PCR and Set B primers of conserved region in a nested PCR
      reaction. Using T801 and T835 primers TTV or viruses of TTV family were detected
      in 16 out of 50 sera tested (32%). Fourteen out of the same 50 sera (28%) were
      positive for TTV using Set B primers. Totally 20 sera were positive using both
      primers (40%). Ten sera were detected with both sets of primers, six sera with
      T801 and T935 primers and only four sera were positive using Set B primers for
      TTV. Different patterns of the detection of the virus with the two different sets
      of primers suggests the possibility of the presence of different genotypes of TTV
      in domestic village chickens and the possibility of the transmission of the virus
      from human to village chickens and vice versa. This necessitates further
      investigations. 

PMID- 25593688
TI  - Serum troponin I as an indicator of myocarditis in lambs affected with foot and
      mouth disease.
AB  - Foot and mouth disease (FMD) is a highly contagious viral disease of cloven
      hooved livestock and wildlife results to relatively high mortality in young
      animals. Despite the numerous reports of FMD-related death in neonates, there is
      little data available on various aspects of FMD in lambs. This report describes
      myocarditis associated with FMD in five, one week to three months old lambs. The
      lambs were depressed and afebrile and two of lambs showed foamy salivation
      associated with shallow ulcers in oral cavity. Electrocardiography (ECG) revealed
      sinus tachycardia, multifocal ventricular premature beats and ventricular
      fibrillation. Serum biochemistry showed high levels of troponin I concentration
      and CK and AST activity. In Pathology, there were multiple pale areas in the
      subepicardial and subendocardial muscles and; widespread degeneration and
      coagulative necrosis of myocardium. The serum troponin I assay and ECG can be
      used for diagnosis of myocarditis and prognosis of affected lambs during FMD
      outbreak. 

PMID- 25593689
TI  - Rectal diverticulum in a terrier dog: A case report.
AB  - Rectal diverticulum is a rare condition in dogs characterized by formation of a
      pouch or sac due to hernial protrusion of the mucous membranes through a defect
      in the muscular coat of the rectum. A 12-year-old male terrier dog was admitted
      with a history of a left perineal swelling, dyschezia and tenesmus during the
      last five months. Digital rectal examination identified a weakness in the left
      pelvic diaphragm and feces-filled sac within the lateral wall of the rectum.
      Positive contrast radiography showed a marked solitary diverticulum (3.5 * 4 *
      4.5 cm) with wide-orifice neck arising from the left rectal wall. Using a lateral
      approach, a large rectal diverticulum was found and diverticulectomy following
      standard herniorrhaphy was performed. The dog recovered uneventfully with no
      signs of dyschezia during the next three years. Diverticulectomy by lateral
      approach and perineal herniorrhaphy produced excellent results. 

PMID- 25593690
TI  - In experienced hands...: the current challenges of laparoscopic education.

PMID- 25593691
TI  - Obesity and Women's Health.

PMID- 25593692
TI  - Identification of peripartum near-miss for perinatal audit.
AB  - INTRODUCTION: Today, perinatal audit focuses basically on cases of perinatal
      mortality. In most centres in Western Europe, perinatal mortality is low.
      Identification of metabolic acidosis at birth may increase index cases eligible
      for evaluation of perinatal care, and this might improve quality of perinatal
      audit. The aim of this study is to assess the incidence of metabolic acidosis at
      birth in order to estimate its impact on perinatal audit. PATIENTS AND METHODS:
      Cord blood was analysed for every neonate born between January 1, 2010 and
      December 31, 2012 in Ziekenhuis Oost-Limburg, Genk. Acidosis was defined as an
      umbilical arterial pH <= 7.05 with or without a venous pH <= 7.17. Respiratory
      acidosis (RA) was defined as acidosis with normal base excess, and metabolic
      acidosis (MA) was defined as acidosis with an arterial or venous base excess <= 
      10 mmol/L. In case of failed cord blood sampling, 5 minute Apgar score <= 6 was
      considered as the clinical equivalent of MA. Retrospective chart review of
      obstetric and paediatric files was performed for all cases of MA, together with
      review of paediatric follow-up charts from at least 6 months after birth.
      Perinatal asphyxia was defined as biochemical evidence for MA at birth,
      associated with early onset neonatal encephalopathy and long-term symptoms of
      cerebral palsy. RESULTS: In a total of 6614 babies, perinatal death up to 7 days
      of life occurred in 40 babies (6.00/00). Acidosis was present in 183 neonates
      (2.8%), of which 130 (2.0%) had RA and 53 (0.8%) had MA. Of the 173 neonates with
      unknown pH values, 6 had Apgar scores <= 6. Of 59 babies born with MA or its
      clinical equivalent, 52 (88.1%) showed no neurologic symptoms at birth. Two
      (3.4%) died in the early neonatal period, one after abruptio placentae and one
      due to chorioamnionitis and severe prematurity. Five (8.5%) MA babies had
      symptoms of early onset neonatal encephalopathy, which recovered in three (5.1%),
      and persisted long-term in two others (3.4%). The two babies with cerebral palsy
      (prevalence 1/3300) were both born after instrumental vaginal delivery for foetal
      distress. CONCLUSION: In our study cohort, the incidence of perinatal mortality
      is 60/00. The incidence of metabolic acidosis is 90/00. Addition of cases of
      metabolic acidosis to those of mortality doubles index cases eligible for
      perinatal audit. The incidence of babies surviving with cerebral palsy after
      metabolic acidosis at birth is very low (0.30/00). Our results suggest that
      instrumental delivery for foetal distress might be a risk factor for metabolic
      acidosis with persisting neurologic dysfunction. Our study illustrates that
      identification of peripartum near-miss is useful for perinatal audit.

PMID- 25593693
TI  - "Now we feel like we did everything we could": A qualitative study into the
      experiences of Dutch patients who travelled to Belgium for infertility treatment.
AB  - Many Dutch infertility patients go to Belgium for treatment every year. This is
      the first qualitative interview study looking into the experiences and
      perspectives of Dutch patients who travel to Belgium for infertility treatment.
      We recruited 16 heterosexual couples and one single woman to ensure maximal
      diversity in age, distance to the clinic, type of treatment and number of
      previously failed cycles. The interview data was analysed using inductive
      thematic analysis. The central theme in the data was that going to Belgium was
      the next step. The Dutch patients believed that the quality of care was very high
      in Belgium and that in taking this step, they did everything they could to
      achieve a pregnancy. 

PMID- 25593694
TI  - Reproductive outcome after IVF following hysteroscopic division of incomplete
      uterine septum/arcuate uterine anomaly in women with primary infertility.
AB  - OBJECTIVE: To determine reproductive outcome after in-vitro fertilization/embryo
      transfer (IVF-ET) in women with primary infertility following hysteroscopic
      septoplasty of incomplete uterine septum or arcuate uterine anomaly. METHODS:
      This is a historical cohort study. The study group consisted of 156 consecutive
      patients who underwent a total of 221 cycles of IVF/ET following hysteroscopic
      septoplasty of an incomplete uterine septum or arcuate anomaly (Group 1). The
      control group included 196 consecutive patients with normal endometrial cavity on
      hysteroscopy who underwent a total of 369 cycles of IVF/ET (Group 2). The
      reproductive outcome after the first cycle of IVF-ET and the best reproductive
      outcome of all the cycles the patient underwent were calculated. In addition, we
      compared the reproductive outcome in the study group based on the type of the
      anomalies (septum versus arcuate). RESULTS: In the first fresh cycle, following
      septoplasty, there were significantly higher clinical pregnancy and delivery
      rates in Group 1 (60.3% and 51.3% respectively) compared to Group 2 (38.8% and
      33.2% respectively). However, there was no significant difference between the two
      groups in the clinical pregnancy (74.4% vs. 67.3%) or in the delivery (65.4% vs.
      60.2%) rates per patient, respectively. There was no significant difference in
      the reproductive outcome after IVF-ET between patients who previously had arcuate
      uterine anomaly versus incomplete uterine septum. CONCLUSION: Reproductive
      outcome of IVF-ET after hysteroscopic correction of incomplete uterine
      septum/arcuate uterine anomaly in women with primary infertility is no different
      from women with normal uterine cavity.

PMID- 25593695
TI  - Comparison of hCG triggering versus hCG in combination with a GnRH agonist: a
      prospective randomized controlled trial.
AB  - A prospective randomized controlled trial comparing two groups of ICSI (intra
      cytoplasmatic sperm injection) patients with a different form of triggering the
      final oocyte maturation has been performed. All patients received an ovarian
      stimulation for in vitro fertilisation (IVF) using an antagonist protocol using
      recombinant-FSH -(rec-FSH) and Ganirelix. 120 Patients were randomized into two
      groups with similar clinical parameters. The first group had triggering with hCG,
      whereas the second group received a combination of hCG + GnRH agonist
      (Gonadotropin Releasing Hormone). As the primary endpoint, the number of
      metaphase II oocytes were analysed, the secondary endpoints were the number of
      cumulus oocyte complexes (COC), the number of fertilized oocytes, embryo
      morphology, pregnancy rate and the number of cryopreserved embryos. The mean
      number of MII oocytes in the hCG triggered group was 9.2 compared with 10.3 in
      the hCG-GnRH agonist group. There was no statistically significant difference in
      the number of COCs or pregnancy rates. However, the number of patients who
      received at least one embryo of excellent quality was significantly higher (p =
      0.001) in the group with the combined triggering (45 out of 61 patients or 73.8%)
      versus the group with hCG triggering alone (28 out of 59 patients or 47.5%). The
      number of cryopreserved embryos was also higher in this group. 

PMID- 25593698
TI  - Prevention of infections in an ART laboratory: a reflection on simplistic
      methods.
AB  - Preventative measures combined with reactive remedial actions are generic
      management tools to optimize and protect an entity's core businesses. Differences
      between assisted reproduction technology (ART) laboratories in developing versus
      developed countries include restricted access to, or availability of resources,
      and the prevalence of pathological conditions that are endemic or common in non
      industrialized regions. The aim of this paper is to discuss the prevention of
      infections in an ART laboratory in a low to middle-income country, with reference
      to simplistic risk reduction applications to avoid the introduction and
      transmission of pathogens. Diagnostic and procedural phases will be examined,
      i.e. (i) screening for microbes during patient evaluation, and (ii-iii)
      prevention of environmental and procedural contamination. Preventative action is
      enabled by knowledge of threats and the degree of risk involved. Awareness and
      understanding of the vulnerabilities in an ART system, wherein laboratory
      personnel operate, are invaluable assets when unforeseen equipment failure occurs
      or instant decisions have to be made to safeguard procedures. An inter-connective
      team approach to patient treatment, biosafety training and utilization of
      practical procedures such as semen decontamination, are fundamental tools in a
      laboratory's risk-reduction armoury to prevent and eliminate infectious elements.

PMID- 25593696
TI  - Current view on ductal carcinoma in situ and importance of the margin thresholds:
      A review.
AB  - Ductal carcinoma in situ (DCIS) is a heterogeneous group of diseases that differ
      in biology and clinical behaviour. Until 1980, DCIS represented less than 1% of
      all breast cancer cases. With the increased utilization of mammography, DCIS now
      accounts for 15% to 25% of newly diagnosed breast cancer cases. The Van Nuys
      Prognostic Index (VPNI) is a commonly used tool for ductal carcinoma in situ
      (DCIS) treatment approach. Patient age, tumour size, tumour margins and
      pathological grade are used in order to stratify patients into three groups
      pertaining to risk of local recurrence: low-, intermediate- and high risk.
      Patients in the low-risk subgroup will always be treated with excision alone,
      while in the highest subgroup mastectomy is the safest option. Just like invasive
      breast cancer (IBC) there might be a curative dilemma in the intermediate-risk
      group. Many trials confirm that tumour margins are the most important prognostic
      factor of local recurrence for DCIS patients treated with breast conserving
      surgery alone or with breast conserving surgery plus radiotherapy. In this
      article we focused specifically on the literature concerning margin thresholds. 

PMID- 25593697
TI  - Recurrence of endometriosis after hysterectomy.
AB  - AIM: Persistent or recurrent pain after hysterectomy is one of the most
      frustrating clinical scenarios in benign gynaecology. We attempt to review the
      current evidence regarding the recurrence of pelvic pain after hysterectomy for
      endometriosis. The impact of ovarian conservation, type of hysterectomy and the
      extent of surgical excision were analysed. METHODS: Peer reviewed published
      manuscripts in the English language in the period between 1980 and 2014 were
      reviewed using Pubmed and science direct regarding the incidence, causes and
      recurrence of endometriosis. RESULTS: Sixty-seven articles were identified.
      Incomplete excision of endometriosis is the most predominant reason in the
      literature for the recurrence of endometriosis, and the type of Hysterectomy
      affects the recurrent symptoms mainly by impacting the extent of excision of the
      lesion. Ovarian cyst drainage is associated with the highest rate of ovarian cyst
      reformation within three to six months after surgery. The use of hormone
      replacement therapy is associated with recurrence of pelvic pain in 3.5% of
      cases. No studies addressed the recurrence of endometriosis after standard vs
      robotic assisted hysterectomy. CONCLUSION: A high recurrence rate of 62% is
      reported in advanced stages of endometriosis in which the ovaries were conserved.
      Ovarian conservation carries a 6 fold risk of recurrent pain and 8 folds risk of
      reoperation. The decision has to be weighed taking into consideration the
      patient's age and the impact of early menopause on her life style. The recurrence
      of endometriosis symptoms and pelvic pain are directly correlated to the surgical
      precision and removal of peritoneal and deeply infiltrated disease. Surgical
      effort should always aim to eradicate the endometriotic lesions completely to
      keep the risk of recurrence as low as possible.

PMID- 25593699
TI  - Implementation of hysteroscopy in an infertility clinic: The one-stop uterine
      diagnosis and treatment.
AB  - Magnetic Resonant Imaging (MRI) has demonstrated that we can differentiate the
      uterus in 3 important functional areas. Exploration of the uterus in the
      infertile patient should implement the evaluation of the endometrium, the
      Junctional zone myometrium (JZ), the outer myometrium and the cervical canal.
      Especially the JZ myometrium should receive our close attention in the
      exploration and treatment of the infertile patient. MRI cannot be implemented as
      a screening examination but also limiting the imaging of the womb to a 2 or 3 D
      ultrasound exam only does not meet the scientific requirements of sensitivity and
      specificity. Modern ambulatory uterine diagnosis in a one-stop approach includes
      transvaginal ultrasound, fluid mini Hysteroscopy, contrast sonography and
      endomyometrial tissue sampling. Transvaginal Ultrasound being the gold standard
      for global uterine screening has a cardinal importance for diagnosis of
      myometrial disorders and uterine congenital malformations whereas hysteroscopy
      remains the gold standard for the evaluation of the endometrium and cervical
      canal. The major challenge remains to perform a tissue sampling of the endo
      myometrium in an ambulatory, patient friendly and reliable way for which the
      newly designed Trophy hysteroscope provide a satisfactory answer. This one-stop
      approach opens a total new and advanced dimension to the screening, diagnosis and
      treatment of uterine pathology in the infertile patient. 

PMID- 25593700
TI  - Excellence needs training "Certified programme in endoscopic surgery".
AB  - The complexity of modern surgery has increased the demands and challenges to
      surgical education and quality control. Today the endoscopic approach is
      preferred because it increases the surgical possibilities and decreases patient
      discomfort. Implementing endoscopic surgery without specific training leads to
      decrease in surgical performance and increase in patient morbidity and mortality.
      Research of the European Academy for Gynaecological Surgery (+he Academy) has
      resulted in the establishment of a structured certification and diploma programme
      with three levels of expertise. One level should be passed to obtain access to
      the next level. Furthermore one should first pass +he Academy skill exam before
      entering the clinical surgical competence programme. The European Society for
      Gynaecological Endoscopy (ESGE) has defined the different diplomas, whereas the
      Bachelor diploma is seen as a prerequisite to start the in OR one to one clinical
      training aiming to provide endoscopic skilled individuals to the clinical one to
      one training. Further diplomas are the Minimal invasive Gynaecological Surgeon
      (MIGS), master in hysteroscopy and the laparoscopic pelvic surgeon. This
      programme is based on the best available scientific evidence. It counteracts the
      problem of the traditional surgical apprentice tutor model and increases patient
      safety and surgical performance. It is seen as a major step toward
      standardization of endoscopic surgical training in general. 

PMID- 25593701
TI  - Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards
      syndrome) in a consecutive series of 47 cases.
AB  - OBJECTIVE: To determine and list the variety of the predominant appeal signs
      leading to referral and their accompanying features found during specialized
      ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. MATERIALS AND
      METHODS: In a period of thirty years, 1110 cases of foetal malformations were
      detected during specialized echographic evaluation. 47 Of these cases were
      foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs
      leading to referral, the difference and overlap in presenting signs between both
      syndromes and when the data were available, we also compared the echographic
      signs with the foetal pathology. RESULTS: In foetuses with trisomy 13 the most
      common malformations were craniofacial defects, cerebral malformations and
      genitourinary tract anomalies. The most common malformations associated with
      trisomy 18 were limb abnormalities and intrauterine growth restriction. Most
      malformations were predominant in trisomy 18, except for genitourinary tract
      anomalies. In most cases the sonographic signs correlated with the pathology
      findings. CONCLUSION: Trisomy 13 as well as trisomy 18 are characterized by a
      number of various malformations in the foetus. Most of the ultrasound features
      were predominant in foetuses with trisomy 18. Mostly the foetal pathology
      correlated with the sonographic evaluation.

PMID- 25593702
TI  - Disseminated ovarian Growing Teratoma Syndrome: a case -report highlighting
      surgical safety issues.
AB  - The ovarian Growing Teratoma Syndrome (GTS) is a rare condition among patients
      with primary Non-Seminomatous Germ Cell Tumours (NSGCT) presenting with enlarging
      masses during or after appropriate chemotherapy in the context of normalized
      serum markers. Several modes of dissemination are suggested, with the most
      frequent site of metastasis being the peritoneum. We report a case of a young
      patient with primary ovarian mixed NSGCT, who presented with Growing Teratoma
      Syndrome not only in the peritoneum but also within a trocar site after an
      initial surgery consisting in the laparoscopic morcellation and extraction of the
      ovarian neoplasm. Beside the rarity of this clinical entity, it also demonstrates
      the utmost importance of the safe laparoscopic management of all complex ovarian
      masses. 

PMID- 25593703
TI  - Subliminal versus supraliminal stimuli activate neural responses in anterior
      cingulate cortex, fusiform gyrus and insula: a meta-analysis of fMRI studies.
AB  - BACKGROUND: Non-conscious neural activation may underlie various psychological
      functions in health and disorder. However, the neural substrates of non-conscious
      processing have not been entirely elucidated. Examining the differential effects
      of arousing stimuli that are consciously, versus unconsciously perceived will
      improve our knowledge of neural circuitry involved in non-conscious perception.
      Here we conduct preliminary analyses of neural activation in studies that have
      used both subliminal and supraliminal presentation of the same stimulus. METHODS:
      We use Activation Likelihood Estimation (ALE) to examine functional Magnetic
      Resonance Imaging (fMRI) studies that uniquely present the same stimuli
      subliminally and supraliminally to healthy participants during functional
      magnetic resonance imaging (fMRI). We included a total of 193 foci from 9 studies
      representing subliminal stimulation and 315 foci from 10 studies representing
      supraliminal stimulation. RESULTS: The anterior cingulate cortex is significantly
      activated during both subliminal and supraliminal stimulus presentation.
      Subliminal stimuli are linked to significantly increased activation in the right
      fusiform gyrus and right insula. Supraliminal stimuli show significantly
      increased activation in the left rostral anterior cingulate. CONCLUSIONS: Non
      conscious processing of arousing stimuli may involve primary visual areas and may
      also recruit the insula, a brain area involved in eventual interoceptive
      awareness. The anterior cingulate is perhaps a key brain region for the
      integration of conscious and non-conscious processing. These preliminary data
      provide candidate brain regions for further study in to the neural correlates of
      conscious experience.

PMID- 25593704
TI  - Antineutrophil cytoplasmic antibody-positive conversion and microscopic
      polyangiitis development in patients with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Increasing evidence indicates that antineutrophil cytoplasmic
      antibody (ANCA)-positive conversion occurs in patients initially diagnosed with
      idiopathic pulmonary fibrosis (IPF) and as a result, some of these patients
      develop microscopic polyangiitis (MPA). However, the incidence density of these
      patients is not well known. OBJECTIVES: To explore the incidence of ANCA-positive
      conversion and development of MPA during the disease course in patients with IPF
      and to evaluate whether corticosteroid therapy reduces MPA development in
      patients with IPF with myeloperoxidase (MPO)-ANCA positivity at diagnosis or who
      later acquire MPO-ANCA positivity. METHODS: We retrospectively analysed the
      medical records of 504 Asian patients with IPF treated at our institution in
      Saitama, Japan. RESULTS: Of the 504 patients with IPF, 20 (4.0%) had MPO-ANCA and
      16 (3.2%) had PR-3-ANCA when first evaluated. In 264 of 504 patients with IPF,
      ANCA was measured repeatedly and seroconversion to MPO-ANCA and PR3-ANCA occurred
      in 15 (5.7%) and 14 (5.3%) patients, respectively, and 9 of 35 patients who were
      either MPO-ANCA positive at IPF diagnosis or who subsequently seroconverted
      developed MPA. None of the nine patients who developed MPA had been previously
      treated with steroids. The incidence of MPA tended to be lower in patients
      treated than not treated with corticosteroids although this was not statistically
      significant. CONCLUSIONS: Some patients with IPF with MPO-ANCA positivity at IPF
      diagnosis or with MPO-ANCA-positive conversion during follow-up developed MPA.
      Clinical trials to determine whether corticosteroid therapy can reduce MPA
      development and prolong survival in MPO-ANCA-positive patients with IPF should be
      considered.

PMID- 25593705
TI  - An observational study of PM10 and hospital admissions for acute exacerbations of
      chronic respiratory disease in Tasmania, Australia 1992-2002.
AB  - OBJECTIVE: Particulate matter with a diameter below 10 u (PM10) has been a major
      concern in the Tamar Valley, Launceston, where wood heaters are extensively used.
      We examined the relationship between PM10 levels, meteorological variables,
      respiratory medications and hospital admissions for respiratory disease over the
      decade 1992-2002. METHODS: PM10 levels were provided by the Department of Primary
      Industry Water, Parks and Environment, and meteorological variables from the
      Bureau of Meteorology. We obtained hospital discharge codes for the Launceston
      General Hospital. Poisson regression was used for statistical analyses. RESULTS:
      Mean daily PM10 levels declined from 50.7 to 16.5 MUg/m(3). Hospitalisations for
      asthma decreased from 29 to 21 per month, whereas chronic obstructive pulmonary
      disease (COPD) increased and bronchitis/bronchiolitis remained unchanged. We
      found a 10 MUg/m(3) increase in PM10 to be associated with a 4% increase in
      admissions for acute bronchitis/bronchiolitis (p0.05), but no association with
      asthma or COPD was found. All respiratory diseases showed seasonal patterns of
      hospitalisation. CONCLUSIONS: This is the first long-term study in Australia to
      demonstrate an association between PM10 levels and respiratory diseases. Reducing
      exposure to PM10 may decrease hospital admissions for respiratory diseases.
      IMPLICATION: Better preventive measures, including sustained public health
      initiatives to combat air pollution, are required to reduce respiratory
      morbidity.

PMID- 25593706
TI  - Developing a vaccine for human rhinoviruses.
AB  - Rhinoviruses (RV's) are common human pathogens of the respiratory tract being the
      most frequent cause of mild diseases of the upper respiratory tract (common cold)
      but more importantly they are a major initiator of acute exacerbations of chronic
      airway diseases. Infections can be life threatening in the latter context however
      RV -induced common colds have an associated economic cost from loss of
      productivity due to absence from work or school. There are no appropriate
      antiviral therapies available and vaccine strategies have failed because of the
      large number of viral serotypes and the lack of cross-serotype protection
      generated. Here, approaches past and present for development of a vaccine to
      these widespread human pathogens are highlighted.

PMID- 25593707
TI  - Protective effects of metformin on renal tubular cells.

PMID- 25593709
TI  - Effectiveness of mindfulness-based stress reduction intervention for health
      related quality of life in drug-dependent males.
AB  - BACKGROUND: Nowadays drug dependence has become one of the main concerns
      worldwide. Indeed, drug dependence and abuse have become personal, social and,
      health problems that intensively threat human resources. OBJECTIVES: This study
      aimed to examine the effect of mindfulness-based stress reduction (MBSR) on
      health-related quality of life (HRQOL) in drug-dependent males. PATIENTS AND
      METHODS: An experimental research with pretest/posttest design and a control
      group was conducted on 49 drug-dependent males. The selected individuals were
      randomly allocated to the study groups (24 to the experimental and 25 to the
      control groups). Afterwards, the Short Form Health Survey for HRQOL (SF-36)
      questionnaire was completed by participants. Subsequently, the experiment group
      experienced eight 90-minute sessions of training in MBSR. At the end of the
      training, the subjects were evaluated once again by SF-36. The independent
      samples t test and analysis of covariance (ANCOVA) were used to analyses data.
      RESULTS: The results suggested that the mean differences between groups regarding
      scales of role emotional, vitality, mental health, social functioning, and bodily
      pain were statistically significant (P < 0.05). CONCLUSIONS: Using MBSR is
      recommended for improving HRQOL in drug-dependent males who are undergoing
      treatment for their drug dependence in addiction treatment center; however, more
      studies concerning different drugs as well as drug dependence in women must be
      performed.

PMID- 25593708
TI  - Factor structure of the Iranian version of 12-item general health questionnaire.
AB  - BACKGROUND: The 12-Item General Health (GHQ-12) questionnaire is one of the most
      commonly used instruments in screening studies on mental health. OBJECTIVES: The
      current study aimed to examine the factor structure of the GHQ-12 questionnaire
      among the students in Iran. MATERIALS AND METHODS: It was a cross-sectional study
      in which 428 university students were recruited and completed the GHQ-12.
      Reliability of the GHQ-12 was evaluated using the Cronbach's alpha and the split
      half method by applying the Spearman-Brown coefficient. Factor structure of the
      questionnaire was extracted by exploratory factor analysis (EFA). Confirmatory
      factor analysis (CFA) was conducted to assess how well the EFA extracted model
      fitted the observed data. RESULTS: The mean age of the participants was 22.83
      years (SD = 3.09). Most of them were female (56.1%) and 81% were unemployed. The
      Cronbach's alpha coefficient for the Iranian version of GHQ-12 was 0.85. Using
      the split-half method, the alpha for the social dysfunction was found to be 0.77;
      it was 0.76 for the psychological distress. The principal component analysis
      revealed a two-factor structure for the questionnaire including social
      dysfunction and psychological distress that explained 48% of the observed
      variances. The confirmatory factor analysis was showed fit for the data.
      CONCLUSIONS: The current study findings confirm that the Iranian version of GHQ
      12 has a good factor structure and is a reliable and valid instrument to measure
      psychological distress and social dysfunction.

PMID- 25593710
TI  - The ability of bispectral-guided management compared to routine monitoring for
      reflecting awareness rate in patients undergoing abdominal surgery.
AB  - BACKGROUND: Awareness during general anesthesia in different types of surgery is
      an important described adverse event. Bispectral (BIS) monitoring is one of the
      recent techniques proposed to monitor the depth of anesthesia. OBJECTIVES: The
      present study tested the hypothesis that the awareness rate and changes in
      hemodynamic parameters within anesthesia would be lower in patients allocated to
      BIS-guided management than those allocated to routine monitoring. MATERIALS AND
      METHODS: In total, 333 adult patients with the American Society of
      Anesthesiologists (ASA) physical status I-III, aged between 18 and 65 years
      scheduled for elective abdominal surgery under general anesthesia were included
      in this randomized double-blind placebo controlled trial. Patients were randomly
      allocated to BIS monitoring (n = 163) or routine monitoring (n = 170). BIS values
      and hemodynamic parameters including systolic blood pressure (SBP), diastolic
      blood pressure (DBP), heart rate (HR), and SPO2 were marked before induction
      (control value), after intubation and laryngoscopy, at intubation, after
      incision, and also during the operation every 15 minutes until extubation.
      RESULTS: The overall incidence of awareness in the BIS and routine monitoring
      groups were 5.5% and 4.1%, which was not significantly different. There were no
      significant differences in hemodynamic indices including SBP, DBP, HR, and SPO2
      before induction of anesthesia between the two groups. These between-group
      differences in the studied indices remained insignificant at different time
      points after anesthesia induction as well as post ICU hospitalization.
      Furthermore, the trend of changes in hemodynamic parameters was comparable in the
      two groups. CONCLUSIONS: BIS-guided management may not be superior to routine
      monitoring protocols to prevent awareness as well as hemodynamic changes during
      general anesthesia in patients undergoing abdominal surgeries.

PMID- 25593711
TI  - Gastrointestinal basidiobolomycosis accompanied by liver involvement: a case
      report.
AB  - INTRODUCTION: Basidiobolomycosis is a rare disease that, unlike other fungal
      infections, affects immunocompetent individuals. It is caused by an environmental
      saprophyte named the fungus Basidiobolus ranarum. Basidiobolomycosis usually
      appears as a subcutaneous infection. GI basidiobolomycosis is an emerging
      disease, and the colon is the most frequent involved part of the GI tract. CASE
      PRESENTATION: The present study presents a middle-aged lady suffered from
      basidiobolomycosis with concomitant lesions in the cecum and liver involvement.
      This disease is extremely rare in adults and only a few cases have been reported
      so far. CONCLUSIONS: GI basidiobolomycosis is a very rare disease which resembles
      as an infiltrative, infectious, or inflammatory process. Concomitant liver and
      bowel involvement is extremely rare too. It is an aggressive disease which has a
      high mortality rate despite treatments like surgical resection and prolonged
      antifungal therapy.

PMID- 25593712
TI  - The bridge between real and ideal: students perception on quality gap in reality
      and their educational expectations.
AB  - BACKGROUND: Studies in higher education indicated that students' expectation for
      their educational services are not provided sufficiently, particularly in
      developing countries that implies on gap between the students perception on
      current situation and their expectations from educational services. OBJECTIVES:
      The aim of this study was to determine the gap between student perception and
      expectations of students in various levels of the undergraduate educational
      courses at Urmia University of Medical Sciences, Iran. PATIENTS AND METHODS: This
      is a longitudinal study, which was conducted in academic year 2007-2008 at the
      Urmia University of Medical Sciences. In total, 173 students were selected as
      sample size, among various courses. SERVQUAL questionnaire was used as
      instrument. Descriptive statistics following by Friedman and Wilcoxon tests were
      used to determining significance of quality gap between five dimensions and to
      evaluate significant gap between student perceptions and their expectations,
      respectively. Spearman test was also used to determine the relationship between
      dimensions. RESULTS: In overall, 80% of educational expectations were not meet;
      there was a negative gap at all phrases and dimensions and the gap was more
      negative for educational experts (-1.45 +/- 0.89) compared to teachers (-0.97 +/-
      0.97). The highest gap for teachers was in empathy dimension (-1.11 +/- 1.51),
      while for experts it was in assurance dimension (-1.58 +/- 1). CONCLUSIONS:
      Existences of gap in dimensions indicated that expectations of students are not
      met and it indicates their dissatisfaction, and thus it is a necessity for
      improvement in all dimensions.

PMID- 25593713
TI  - Comparing the effects of aromatherapy with rose oils and warm foot bath on
      anxiety in the first stage of labor in nulliparous women.
AB  - BACKGROUND: Anxiety is the most common emotional response in women during
      delivery, which can be accompanied with adverse effects on fetus and mother.
      OBJECTIVES: This study was conducted to compare the effects of aromatherapy with
      rose oil and warm foot bath on anxiety in the active phase of labor in
      nulliparous women in Tehran, Iran. PATIENTS AND METHODS: This clinical trial
      study was performed after obtaining informed written consent on 120 primigravida
      women randomly assigned into three groups. The experimental group 1 received a 10
      minute inhalation and footbath with oil rose. The experimental group 2 received a
      10-minute warm water footbath. Both interventions were applied at the onset of
      active and transitional phases. Control group, received routine care in labor.
      Anxiety was assessed using visual analogous scale (VASA) at onset of active and
      transitional phases before and after the intervention. Statistical comparison was
      performed using SPSS software version 16 and P < 0.05 was considered significant.
      RESULTS: Anxiety scores in the intervention groups in active phase after
      intervention were significantly lower than the control group (P < 0.001). Anxiety
      scores before and after intervention in intervention groups in transitional phase
      was significantly lower than the control group (P < 0.001). CONCLUSIONS: Using
      aromatherapy and footbath reduces anxiety in active phase in nulliparous women.

PMID- 25593714
TI  - Spontaneous uterine perforation caused by pyometra: a case report.
AB  - INTRODUCTION: Pyometra is an accumulation of purulent material or pus in the
      uterine cavity. Spontaneous perforation of uterus by pyometra is rare. This is a
      clinical presentation and management of a spontaneous perforation of uterine
      caused by pyometra. CASE PRESENTATION: This is a case report on spontaneously
      perforated associated with pyometra secondary to cervical malignancy. The patient
      underwent exploratory laparotomy with total hysterectomy and bilateral salpingo
      oophorectomy. CONCLUSIONS: Spontaneous rupture of pyometra duo to cervical cancer
      in cases of acute abdomen in elderly patients should be considered.

PMID- 25593716
TI  - Comparison of different edge detections and noise reduction on ultrasound images
      of carotid and brachial arteries using a speckle reducing anisotropic diffusion
      filter.
AB  - BACKGROUND: Common carotid artery (CCA) ultrasound with measurement of intima
      media thickness (IMT) is a safe and noninvasive technique for assessing
      subclinical atherosclerosis and determining cardiovascular risks. Moreover, the
      pattern of wall thickening in the brachial artery (BA) is rather diffuse compared
      to the carotid artery and may be a more sensitive indicator of long-term systemic
      exposure to risk factors. Therefore noninvasive evaluation of mechanical
      parameters changes of both arteries has gained the attention of researchers.
      OBJECTIVES: The aim of this study was to compare different edge detection
      techniques with speckle reducing anisotropic diffusion (SRAD) de-noising filter
      in ultrasound images of both arteries. PATIENTS AND METHODS: In a cross-sectional
      design, an examination was performed on ten men with mean age of 40 +/- 5 years
      from September 2012 to March 2013 through random sampling. An ultrasonic
      examination of the left CCA and BA was performed. The program was designed in the
      MATLAB software to extract consecutive images in JPEG format from the AVI.
      Another program was designed in the MATLAB software to apply regions of interest
      (ROI) on the IMT of the posterior wall of common carotid and brachial arteries.
      Next, different edge detections and SRAD filter were applied to the ROI,
      separately. Finally, the program measured mean-squared error (MSE) and peak
      signal to noise ratio (PSNR). RESULTS: The lowest values of MSE and highest
      values of PSNR were achieved by Canny edge detection with de-noising SRAD filter
      for IMT of left CCA and BA in 90 frames. CONCLUSIONS: Based on the result, by
      measuring the MSE and PSNR, this study showed Canny edge detection with SRAD
      filter is better than other edge detections in terms of speckle suppression and
      details preservation in CCA and BA ultrasound images.

PMID- 25593715
TI  - Anxiety, depression, coronary artery disease and diabetes mellitus; an
      association study in ghaem hospital, iran.
AB  - BACKGROUND: There is an increasing trend in the prevalence of coronary artery
      disease (CAD) in Iran. OBJECTIVES: The present study aimed to investigate the
      relationship of anxiety, depression, diabetes and coronary artery disease among
      patients undergoing angiography in Ghaem Hospital, Mashhad, Iran. PATIENTS AND
      METHODS: This case-control study was conducted between September 2011 and August
      2012 among 200 patients undergoing coronary angiography for symptoms of coronary
      disease at Ghaem Hospital, Mashhad, Iran. The control group consisted of 697
      healthy adults recruited from the individuals who attended the clinic for routine
      medical checkups or pre-employment examinations. The Beck anxiety and depression
      inventory scores and fasting blood glucose results were assessed in all the
      subjects. Data were analyzed using SPSS version 16. P < 0.05 was regarded as
      statistically significant. RESULTS: The mean age of patients was 57.52 +/- 9.33
      years old and for the control group it was 55.35 +/- 8.45 years; there was no
      significant difference between the subjects (P = 0.647) regarding age. There was
      also no significant difference in gender distribution between the patients and
      control groups (P = 0.205). There was however a significant difference in anxiety
      and depression scores between the patients and healthy controls (P < 0.001).
      There was a significant positive correlation between anxiety score and depression
      score in both groups when data were analyzed by Pearson test. (P < 0.001, r =
      0.604 and r = 0.521). Moreover, there was a significant positive linear
      correlation between the depression/anxiety scores and fasting blood glucose
      concentrations in the patients group (r = 0.3, P < 0.001) and a weak negative
      correlation in the healthy controls (r = -0.096, P < 0.05). CONCLUSIONS:
      Depression and anxiety are potentially important factors among patients with
      angiographically-defined CAD. There appear to be significant associations between
      glucose tolerance and anxiety and depression in these patients.

PMID- 25593717
TI  - Developing a valid and reliable instrument to predict the protective sexual
      behaviors in women at risk of human immunodeficiency virus.
AB  - BACKGROUND: One much needed tool to assist with the monitoring and evaluation of
      Human Immunodeficiency Virus (HIV) prevention programs is to provide a valid
      instrument to measure protective sexual behavior and related factors. OBJECTIVES:
      The current study aimed to design a valid and reliable instrument to predict the
      protective sexual behaviors of women at risk of HIV in Iran. PATIENTS AND
      METHODS: The current study was a sequential mixed cross-sectional and
      methodological research. Initially, via a qualitative research, constructs and
      factors associated with sexual protective behavior of women at risk were
      identified through 25 in-depth interviews. The questionnaire on predictors of
      protective sexual behaviors in women at risk of HIV (PSPB) was designed based on
      a qualitative study, and then its qualitative validity, content, and construct
      validity were evaluated. Exploratory factor analysis was performed and 200 women
      at risk participated. RESULTS: Seven concepts emerged after exploratory factor
      analysis of the 48 items. The content validity ratio (CVR) of the questionnaire
      constructs were 0.55 to 0.76, and content validity index (CVI) structure was 0.86
      to 0.95. Cronbach's alpha coefficient for the entire questionnaire was 0.78, and
      correlation coefficient of the test-retest reliability for the constructs was
      from 0.73 to 0.89. CONCLUSIONS: The current study proved the capability of the
      predictors of sexual protective behavior in women at risk for HIV questionnaire
      as a valid and reliable instrument for the Iranian community.

PMID- 25593718
TI  - The association of deep vein thrombosis with cancer treatment modality:
      chemotherapy or surgery?
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a well-recognized complication in
      patients with cancer. Chemotherapy and cancer surgery increase the risk of DVT in
      these patients. There are a few reports about the prevalence of DVT in patients
      with cancer regarding different managing modalities. OBJECTIVES: This study aimed
      to assess the prevalence of DVT in patients with cancer, who were hospitalized in
      teaching hospitals, according to their treatment intervention. PATIENTS AND
      METHODS: A cross-sectional retrospective study was conducted on 602 patients with
      cancer in Kerman, Iran, during years 2006-2007. Among the subjects, 301 had been
      operated and the rest had received chemotherapy. The prevalence of DVT was
      determined based on patients' variables, cancer factors, and therapeutic
      modalities. RESULTS: Totally, 349 subjects (58%) were male. DVT incidence was
      19.9%, most of the cases were over 40 years of age (82.2%), and 21.2% of males
      and 18.2% of females had developed DVT. The prevalence of DVT in chemotherapy
      group was higher than that in surgery group (21.9% and 17.9%, respectively);
      however, this difference was statistically insignificant. DVT developed more
      frequently in lung cancer (42%) with small cell carcinoma being the most common
      pathologic finding (42.9%) in those with lung cancer (P = 0.0001). CONCLUSIONS:
      DVT occurs frequently in patients with malignancies. In this study, there was no
      association between DVT prevalence and age as well as sex; nonetheless, the
      prevalence was significantly higher in some sites and in patients with certain
      pathologies. Although DVT prevalence was higher in chemotherapy than in surgery,
      the difference was insignificant. Informing patients with cancer about symptoms
      of DVT and prophylactic interventions are warranted.

PMID- 25593719
TI  - Prolonged survival of a patient with pelvic recurrence of ovarian malignant mixed
      mullerian tumor after chemoradiotherapy.
AB  - INTRODUCTION: Malignant Mixed Mullerian Tumor (MMMT) is a very rare tumor,
      accounting for less than 1% of all ovarian cancers. CASE PRESENTATION: We present
      a 64-year-old woman with stage III MMMT of ovary that was treated with platinum
      based chemotherapy after optimal cytoreductive surgery. After 25 months of being
      disease free, she had a pelvic recurrence and a good response to
      chemoradiotherapy. CONCLUSIONS: Optimal cytoreductive surgery and chemotherapy
      may be the best treatment in MMMT but more discussion and experiences are needed
      regarding the effectiveness of radiotherapy.

PMID- 25593720
TI  - Challenges of Iranian adolescents for preventing dental caries.
AB  - BACKGROUND: Oral health plays a vital role in people's general health and well
      being. With regard to the costly treatments of oral diseases, preventive programs
      need to be designed for dental caries based on children's perspectives.
      OBJECTIVES: The purpose of this study was to describe and explore challenges for
      caring dental health based on children's perspectives. PATIENTS AND METHODS: A
      qualitative design with content analysis approach was applied to collect and
      analyze the perspectives of students about factors influencing oral and dental
      care. Eighteen Iranian students in 8 guidance schools were chosen through the
      purposive sampling. Semi-structured interviews were held for data gathering. In
      order to support the validity and rigor of the data, different criteria such as
      acceptability, confirmability, and transferability were utilized. RESULTS: During
      data analysis, four main themes developed: "barriers to dental health,"
      "maintaining dental health," "uncertainty in decision-making" and "supportive
      factors". "Uncertainty in decision-making" and "barriers to dental health" were
      the main challenges for preventing dental caries among adolescents. CONCLUSIONS:
      "Certainty in decision-making" to maintain dental health depends on overcoming
      the barriers of dental health. Further research is needed to confirm the findings
      of this study.

PMID- 25593721
TI  - Heart hydatid cyst close to the left descending artery in a thirteen-year-old
      boy.
AB  - INTRODUCTION: Hydatid cyst is a significant health problem in underdeveloped and
      developing countries, particularly among sheep breeders. Although cardiac
      involvement is seen only in 0.2% to 3% of the cases, early diagnosis and
      treatment are important. CASE PRESENTATION: A 13-year-old boy with dyspnea and
      atypical pericardial type chest pain for three months was referred to us. Chest X
      ray revealed linear calcification in the left side of the heart. Computed
      tomography demonstrated a cyst with peripheral calcification and without internal
      septation in the lateral left ventricle (LV) myocardium. Serologic IgG test was
      positive for Echinococcosis. No other cyst was seen in the other organs such as
      the lungs and liver. By midline sternotomy on pump, an incision was made 2-cm
      lateral to the left ascending artery through the LV myocardium and without
      entering any cardiac chamber. After injecting hypertonic (5%) saline, the cyst
      was punctured and its fluid contents were aspirated, the cyst was enucleated, and
      the cavity marsupialization was done for protection of the myocardium. LV
      ejection fraction before operation was 40% but after operation and repairing LV
      myocardium, ejection fraction increased to 50% in. Histopathologic examination
      confirmed a hydatid cyst. CONCLUSIONS: In myocardial hydatid cysts, we recommend
      a direct approach without entering the cardiac chambers to avoid dissemination of
      the infection. We recommend excision of the germinative membrane without
      capitonnage to avoid impairment of myocardial contraction.

PMID- 25593722
TI  - Estimating the annual risk of tuberculosis infection and disease in southeast of
      iran using the bayesian mixture method.
AB  - BACKGROUND: Tuberculosis is still a public health concern in Iran. The main
      challenge in monitoring epidemiological status of tuberculosis is to estimate its
      incidence accurately. OBJECTIVES: We used a newly developed approach to estimate
      the incidence of tuberculosis in Sistan, an endemic area in southeast of Iran in
      2012-13. PATIENTS AND METHODS: This cross-sectional study was conducted on school
      children aged 6-9 years. We estimated a required sample size of 6350. Study
      participants were selected using stratified two-stage cluster sampling method and
      recruited in a tuberculin skin test survey. Indurations were assessed after 72
      hours of the injection and their distributions were plotted. Prevalence and
      annual risk of tuberculosis infection (ARTI) were estimated using the Bayesian
      mixture model and some traditional methods. The incidence of active disease was
      calculated using the Markov Chain Monte Carlo technique. RESULTS: We assumed
      weibull, normal and normal as the best distributions for indurations due to
      atypical reactions, BCG (Bacillus Calmette-Guerin) reactions and Mycobacterium
      tuberculosis infection, respectively. The estimated infection prevalence and ARTI
      were 3.6% (95%CI: 3.1, 4.1) and 0.48%, respectively. These estimates were lower
      than those obtained from the traditional methods. The incidence of active
      tuberculosis was estimated as 107 (87-149) per 100000 population with a CDR of
      54% (40%-68%). CONCLUSIONS: Although the mixture model showed slightly lower
      estimates than the traditional methods, it seems that this method might generate
      more accurate results for deep exploration of tuberculosis endemicity. Besides,
      we found that Sistan is a high endemic area for tuberculosis in Iran with a low
      case detection rate.

PMID- 25593723
TI  - Quality assessment of randomized control trials applied psychotherapy for chronic
      pains in iran: a systematic review of domestic trials.
AB  - CONTEXT: Keeping in mind the burden of psychotherapy can play a crucial role
      concerning chronic pain (CP). Psychotherapy techniques are widely used to relief
      Chronic Pain (CP) worldwide. Appling psychotherapy needs to consider both
      individual and popular cultures. In addition to international requirements;
      nation-wide legitimacy should be regarded too. Psychological methods have
      provided a lot of articles in Iran, but they were neglected by the reviewers
      because the documents only have abstracts in English. The current study aimed to
      assess all Farsi Randomized Control Trials (RCTs) addressing psychotherapy to
      relieve chronic pains. EVIDENCE ACQUISITION: Six nation-wide medical databases
      were investigated in 2012 using the keyword chronic pain in the Abstracts,
      systematically. Appling PICO question format (patient problem or population,
      intervention, comparison, and outcomes) all the interventional studies were
      reviewed for eligibility. Retrieving full text (in Farsi) and making the articles
      indistinguishable, two native reviewers assessed the quality of the articles
      independently using Jadad scale. RESULTS: Inclusion criteria met 1542 abstracts.
      After refining and excluding, seventeen experimental studies were retrieved and
      evaluated. Mean quality score of Jadad was 1.53 +/- 1.37 (median = 1.0).
      Cognitive Behavior Therapy (CBT) was the dominant approach (11 out of 17) and the
      majority (6 out of 17 studies) of the treated cases was Low Back Pain (LBP).
      Patient-therapist gender adjustment has clearly reported in most of the studies,
      based on the requirements. CONCLUSIONS: Cognitive Behavior Therapy was more
      effective than the other psychotherapy approaches relieving chronic pain in the
      studies. Well-designed studies and comprehensive clarification of the studies
      demonstrating groups, intervention, follow-up and drop outs can improve the
      quality of the RCTs.

PMID- 25593725
TI  - Effect of biochanin a on serum visfatin level of streptozocin-induced diabetic
      rats.
AB  - BACKGROUND: Bioflavonoids are well known for their multi directional biologic
      activity including antidiabetic effect. It has been demonstrated that flavonoids
      can act as insulin secretagogue or insulin mimetic agents. OBJECTIVES: This
      experimental study was designed in Arak University of Medical Sciences, Arak,
      Iran, to investigate the effects of biochanin A (a bioflavonoid) on fasting blood
      glucose (FBG), body weight, glycosylated hemoglobin (HbA1c), lipid profile, serum
      enzymes, and visfatin of streptozocin-induced diabetic rats. PATIENTS AND
      METHODS: We used 24 male Wistar rats and randomly allocated them to four groups
      of six rats. One group was randomly assigned as control and diabetes was induced
      in three other groups by administration of streptozocin (35 mg/kg of body weight)
      intraperitoneally. The groups received the following treatments: group 1
      (control), 5% DMSO; group 2 (diabetic control), 0.5% DMSO; and group 3 and 4,
      respectively 10 and 15 mg/kg biochanin A for 30 days. Body weight and biochemical
      parameters including FBG, HbA1c, lipid profile, aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), alkaline phosphatase (ALP), and visfatin were
      measured in all rats. RESULTS: FBG level was significantly reduced in treated
      diabetic rats (139.8 +/- 9.3 and 206 +/- 11 mg/dL in groups 3 and 4,
      respectively) in comparison to the diabetic control (295.1 +/- 14 mg/dL) (P <
      0.05). Administration of biochanin A significantly decreased HbA1c in group 3
      (6.66 +/- 0.33) and group 4 (7.11 +/- 0.31) in comparison to the diabetic control
      group (8.26 +/- 0.44) (P < 0.05). Levels of serum visfatin were improved to near
      normal levels in the treated rats (249 +/- 35.5 and 161.33 +/- 13.07 in groups 3
      and 4, respectively) in comparison to the diabetic control (302.17 +/- 19.4) (P <
      0.05). Furthermore, biochanin A showed a protective effect against weight loss in
      diabetic rats (P < 0.05). In treated rats, serum total cholesterol, triglyceride,
      and low-density lipoprotein cholesterol (LDL-c) were significantly decreased and
      high-density lipoprotein (HDL-c) was increased in comparison with the diabetic
      control group. In addition, biochanin A restored the altered plasma enzymes (AST,
      ALT, and ALP) activities to near normal. Histopathologic examination of the
      pancreas also indicated that biochanin A had protective effects on beta-cells in
      streptozocin-induced diabetic rats. CONCLUSIONS: This study demonstrated that
      biochanin A possessed hypoglycemic and antilipemic activities and could increase
      visfatin expression, which suggests its beneficial effect in the treatment of
      diabetes.

PMID- 25593724
TI  - A glance at methods for cleft palate repair.
AB  - CONTEXT: Cleft palate is the second most common birth defect and is considered as
      a challenge for pediatric plastic surgeons. There is still a general lack of a
      standard protocol and patients often require multiple surgical interventions
      during their lifetime along with disappointing results. EVIDENCE ACQUISITION:
      PubMed search was undertaken using search terms including 'cleft palate repair',
      'palatal cleft closure', 'cleft palate + stem cells', 'cleft palate + plasma rich
      platelet', 'cleft palate + scaffold', 'palatal tissue engineering', and 'bone
      tissue engineering'. The found articles were included if they defined a
      therapeutic strategy and/or assessed a new technique. RESULTS: We reported a
      summary of the key-points concerning cleft palate development, the genes
      involving this defect, current therapeutic strategies, recently novel aspects,
      and future advances in treatments for easy and fast understanding of the
      concepts, rather than a systematic review. In addition, the results were
      integrated with our recent experience. CONCLUSIONS: Tissue engineering may open a
      new window in cleft palate reconstruction. Stem cells and growth factors play key
      roles in this field.

PMID- 25593726
TI  - Main facilitators of smoking among young males in tehran: tehran lipid and
      glucose study.
AB  - BACKGROUND: Smoking is the most preventable risk factor for non-communicable
      diseases and its alarming trend. OBJECTIVES: The aim of this study was to explore
      and determine facilitating factors for smoking in young males, who participated
      in the Tehran Lipid and Glucose Study (TLGS), from their own perspective.
      PATIENTS AND METHODS: This qualitative study was conducted within the framework
      of the TLGS. Participants were young males with 15 to 25 years of age and various
      levels of education. The inductive content analysis approach was used to analyze
      data on the participants' perceptions with regard to smoking facilitators. Data
      collection was conducted through discussions by six semi-structured focus groups
      consisted of five to seven people. All the interviews were transcribed after
      being recorded and analyzed through constant comparative analysis. RESULTS: Two
      main categories derived from the analysis of the data: I) personal needs and
      features; and II) environmental facilitators. The former concept included three
      subcategories: 1) fulfilling essential needs; 2) search for identity; and 3) lack
      of life skills. Environmental facilitators were also divided into two
      subcategories: 1) social patterns; and 2) ease of access. CONCLUSIONS: Tendency
      towards smoking is influenced by different factors. Clarifying these influential
      factors for smoking from the perspective of young males can be important in
      designing effective preventive programs.

PMID- 25593727
TI  - The reasons for using acupuncture for pain relief.
AB  - BACKGROUND: Acupuncture has recently received considerable attention around the
      world due to its cost-effectiveness, few side effects, and well-established
      analgesic properties. OBJECTIVES: The present study aimed to identify the factors
      that might lead to using acupuncture for pain relief. PATIENTS AND METHODS: This
      qualitative study was conducted using conventional content analysis method. The
      study population included eight patients and six highly experienced
      acupuncturists, who were able to express their opinion and were willing to take
      part in the study. The inclusion criteria for patients were being under treatment
      with acupuncture for pain relief or a history of treatment during the last year
      and age > 18 years. All highly trained acupuncturists with minimum of one-year
      active experience were included. The data were collected via semi-structured in
      depth interviews. Categories were extracted through inductive analysis and codes
      and eventually, themes emerged. Data rigor was assured by data collection
      triangulation, participants' variety, and external and members' check. RESULTS:
      Initially, 1311 primary codes were extracted, then the related codes were divided
      into 127 subcategories according to their similarities, and after reduction and
      integration process, 16 categories were developed from subcategories and
      eventually five themes were determined, including conventional medicine
      limitation, efficacy of acupuncture, external promoters, internal promoters, and
      acupuncture inhibitors. CONCLUSIONS: The important factors that affect choosing
      acupuncture for pain relief included conventional medicine limitations, external
      promoters, internal promoters, acupuncture efficacy, and acupuncture inhibitors.
      More interest can be drawn to this technique by basic planning to enhance some of
      the underlying factors and eliminate obstacles to its further applicability.

PMID- 25593728
TI  - Ramadan major dietary patterns.
AB  - BACKGROUND: There has been no data on population based dietary patterns during
      the Ramadan fasting month. OBJECTIVES: The purpose of this study was to detect
      Ramadan major dietary patterns among those who fast in Tehran. MATERIALS AND
      METHODS: This cross-sectional study included 600 subjects, aged 18-65 with body
      mass index (BMI) of 18.5-40, who had decided to fast during Ramadan.
      Anthropometric measurements, usual physical activity level and educational status
      were collected two weeks before Ramadan. Information on Ramadan dietary intakes
      was obtained using a food frequency questionnaire and factor analysis was used to
      identify major dietary patterns. RESULTS: We identified four major dietary
      patterns: 1) Western-like pattern; high in fast foods, salty snacks, nuts,
      potato, fish, poultry, chocolates, juices; 2) high cholesterol and high sweet
      junk food pattern; high in pickles, sweets and condiments, butter and cream,
      canned fish, visceral meats and eggs; 3) Mediterranean-like pattern; high in
      vegetables, olive oil, dates, dairy, dried fruits, fruits, red meats, tea and
      coffee and 4) Ramadan-style pattern; large consumption of Halim, soups,
      porridges, legumes and whole grains, soft drinks, Zoolbia and Bamieh. Age was
      positively and inversely associated with Mediterranean-like (P = 0.003; r = 0.17)
      and Ramadan style (P = 0.1; r = -0.13) dietary pattern, respectively. Pre-Ramadan
      physical activity level was associated with a Mediterranean-like dietary pattern
      (P < 0.0001; r = 0.20). CONCLUSIONS: This study showed a Ramadan-specific dietary
      pattern has unique characteristics, which has not yet been identified as a model
      of dietary pattern. Also, among identified dietary patterns, Mediterranean-like
      was the healthiest.

PMID- 25593729
TI  - The association of health-promoting lifestyle with quality of life among the
      Iranian elderly.
AB  - BACKGROUND: As individuals live a longer life, health-promoting lifestyle (HPL)
      becomes even more essential, particularly with regard to maintaining functional
      independence and improving quality of life (QoL). OBJECTIVES: This study aimed to
      determine the association between QoL and HPL in the Iranian elderly living in
      Shiraz. MATERIALS AND METHODS: This analytical cross-sectional study was
      conducted in 2013 at retirement centers of Shiraz City, Iran. The sample included
      500 elderly who aged > 60 years. Proportional stratified random sampling was used
      to select the elderly from retirement centers. QoL was assessed by the Farsi
      version of Short Form Health Survey questionnaire (SF-36) and HPL was measured by
      health-promoting lifestyle profile (HPLP II). Data were analyzed using
      independent-samples t test, one-way ANOVA, Pearson's correlation, and stepwise
      multiple regression using SPSS 21. RESULTS: There were significant differences in
      QoL in terms of sex, age, education, and marital status. There were significant
      differences in HPL in terms of gender, age and education (P < 0.05) There was a
      statistically significant association between QoL and HPL in the elderly (r =
      0.42, P < 0.05). Based on HPLP II constructs, the significant predicting factors
      of QoL in the elderly consisted of spiritual growth, stress management, and
      physical activity (P < 0.05). CONCLUSIONS: Health providers should improve the
      QoL in the elderly by facilitating HPL through health-promoting interventions,
      which will maintain and increase physical activity, stress management, and
      spiritual growth.

PMID- 25593730
TI  - Anti-inflammatory Activity of Stachys Pilifera Benth.
AB  - BACKGROUND: Stachys pilifera Benth has long been used to treat infectious
      diseases as well as respiratory and rheumatoid disorders in Iranian folk
      medicine. Antioxidants, antitumor, and antimicrobial properties of the plant have
      been reported. OBJECTIVES: This experimental study was designed to evaluate
      systemic and topical anti-inflammatory effects of the hydro-alcoholic extract
      from aerial parts of Stachys pilifera (HESP). MATERIALS AND METHODS: Anti
      inflammatory effects of HESP was studied in four well-known animal models of
      inflammation, including carrageenan- or formalin-induced paw edema in rat
      (thirteen groups, 6 rats per each group), and 12-O-tetradecanoylphorbol-13
      acetate (TPA)- or xylene-induced ear edema in mouse (ten groups, 6 mice per each
      group). The rats received HESP (50-400 mg/ kg) orally 45 minutes before the
      subplantar injection of carrageenan or formalin. In TPA or xylene tests, HESP (1,
      2.5, and 5 mg/ear) was applied topically simultaneous with these phlogistic
      agents on the ear mice. Finally, pathological examination of the inflamed tissues
      (paw and ear) was carried out. RESULTS: Acute toxicity study of the extract
      showed that no rats were killed at 5000 mg/kg (LD50 > 5000 mg/kg). The extract
      (100 and 200 mg/ kg) significantly suppressed carrageenan-induced paw edema 1, 2,
      3, and 4 hours after carrageenan challenge in comparison with the control group
      (P < 0.001). The HESP (100 and 200 mg/kg) also produced a considerable
      antiedematogenic effect in the formalin test over a period of 24 hours (P <
      0.01). Furthermore, topical administration of the HESP (1, 2.5, and 5 mg/ear)
      inhibited TPA- and xylene-induced ear edema in comparison with the control group
      (P < 0.001). The pathological analysis of the paws and ears revealed that HESP
      was capable of reducing tissue destruction, cellular infiltration, and
      subcutaneous edema induced by the indicated phlogistic agents. CONCLUSIONS: The
      present data confirmed systemic and topical anti-inflammatory effects of Stachys
      pilifera which is comparable to indomethacin.

PMID- 25593731
TI  - Nutritional and unhealthy behaviors in women with and without breast cancer.
AB  - BACKGROUND: Breast cancer is the most common malignancy in women. Global
      statistics indicate increasing rates of this cancer. Nutrition, diet, and healthy
      behaviors are among influential factors in prevalence of breast cancer, and
      possibly affect its incidence through inflammatory and immune system responses.
      OBJECTIVES: This study was designed to compare nutritional and unhealthy
      behaviors in women with and without breast cancer referred to Mahdieh Imaging
      Center in Hamadan in 2013. PATIENTS AND METHODS: This cross-sectional study is
      conducted on 232 women with r and without breast cancer referred to Mahdieh
      Imaging Center of Hamadan, Iran) in 2013 using random sampling method. Data were
      collected using nutritional and unhealthy behaviors questionnaires, and analyzed
      with SPSS-17 software using descriptive statistics and Mann-Whitney, independent
      t, and chi-square tests. RESULTS: The mean scores of feeding type in the patients
      with and without breast cancer was 56.14 and 66.25, respectively. Results
      obtained from data analysis showed that there was statistically significant
      difference between the two groups in terms of nutrition (P < 0.001), but no
      relationship was observed between breast cancer and unhealthy behaviors.
      CONCLUSIONS: Given the results, improving skills, training and awareness is
      necessary for women and emphasis on modified diet is recommended as a non-medical
      option for prevention of breast cancer.

PMID- 25593732
TI  - Hepatotoxicity of halogenated inhalational anesthetics.
AB  - CONTEXT: Halogenated inhalational anesthetics are currently the most common drugs
      used for the induction and maintenance of general anesthesia. Postoperative
      hepatic injury has been reported after exposure to these agents. Based on much
      evidence, mechanism of liver toxicity is more likely to be immunoallergic. The
      objective of this review study was to assess available studies on hepatotoxicity
      of these anesthetics. EVIDENCE ACQUISITION: We searched PubMed, Google Scholar,
      Scopus, Index Copernicus, EBSCO and the Cochrane Database using the following
      keywords: "inhalational Anesthetics" and "liver injury"; "inhalational
      anesthetics" and "hepatotoxicity"; "volatile anesthetics" and "liver injury";
      "volatile anesthetics" and hepatotoxicity for the period of 1966 to 2013. Fifty
      two studies were included in this work. RESULTS: All halogenated inhalational
      anesthetics are associated with liver injury. Halothane, enflurane, isoflurane
      and desflurane are metabolized through the metabolic pathway involving cytochrome
      P-450 2E1 (CYP2E1) and produce trifluoroacetylated components; some of which may
      be immunogenic. The severity of hepatotoxicity is associated with the degree by
      which they undergo hepatic metabolism by this cytochrome. However, liver toxicity
      is highly unlikely from sevoflurane as is not metabolized to trifluoroacetyl
      compounds. CONCLUSIONS: Hepatotoxicity of halogenated inhalational anesthetics
      has been well documented in available literature. Halothane-induced liver injury
      was extensively acknowledged; however, the next generation halogenated
      anesthetics have different molecular structures and associated with less
      hepatotoxicity. Although anesthesia-induced hepatitis is not a common occurrence,
      we must consider the association between this disorder and the use of halogenated
      anesthetics.

PMID- 25593733
TI  - In vitro ovine embryo production: the study of seasonal and oocyte recovery
      method effects.
AB  - BACKGROUND: To current knowledge, different oocyte's recovery method and various
      seasons have profound impact on in vitro embryo production (IVEP). OBJECTIVES:
      The aim of this study was to define an efficient recovery method for oocytes
      harvesting from slaughterhouse material in different seasons, and their effects
      on IVEP yield. MATERIALS AND METHODS: Ovaries from slaughtered ewes in breeding
      season (BS) and non-breeding season (NBS) were collected from a local abattoir.
      The oocytes were recovered through aspiration, centrifugation (ORC), puncture and
      slicing, and categorized into three classes (I, oocytes with more than three
      layers of cumulus cells; II, less than three layers with damaged cumulus cells;
      III, denuded oocytes). After cultivation in TCM 199 for 24 hours, matured oocytes
      were subjected to in vitro fertilization (IVF) and in vitro culture (IVC). The
      oocyte recovery using ORC in BS and NBS was significantly higher (P < 0.05)
      compared with other recovery methods. RESULTS: No significant dissimilarities in
      the proportion of oocytes reaching M-II stage were recorded when using different
      oocyte recovery methods in different seasons. Aspiration resulted in lower (P <
      0.05) proportion of class I (BS, 60.0 +/- 2.1; NBS, 51.1 +/- 2.1) compared to ORC
      (BS, 82.0 +/- 1.2; NBS, 70.0 +/- 1.2), slicing (BS, 80.0 +/- 2.1; NBS, 71.0 +/-
      1.4) and puncture (BS, 80.0 +/- 1.5; NBS, 72.0 +/- 2.0). Monospermy and
      blastocyst development rates were significantly higher using ORC than other
      recovery techniques in both BS and NBS. More oocytes with high quality, greater
      blastocyst development and oocyte recovery rates were achieved in BS.
      CONCLUSIONS: The results revealed that oocytes harvesting technique and season
      are effective in the rate of cleavage and blastocysts' development, and suggest
      that despite same meiotic resumption rate in all treatments, it would be better
      to use ORC.

PMID- 25593734
TI  - Nasal Carriage and Resistance Pattern of Multidrug Resistant Staphylococcus
      aureus Among Healthy Children in Kashan, Iran.
AB  - BACKGROUND: Nasal carriage of Staphylococcus aureus is a substantial source of
      human infections. Detection and treatment of nasal carriage in children with
      methicillin-resistant and multidrug resistant S. aureus (MRSA and MDRSA,
      respectively) may be an important modality in prevention of infections.
      OBJECTIVES: This study determined the prevalence, antibiotic resistance patterns
      and risk factors for nasal carriage of MDRSA among healthy children. PATIENTS AND
      METHODS: This cross-sectional study was carried out on 350 one-month to 14-year
      old healthy children in Kashan city, Iran. From all health-care centers, four
      were chosen by simple random sampling. Nasal samples were cultured in blood agar
      medium for S. aureus and antibiotic susceptibility profile was determined by disc
      diffusion and E-test. Risk factors for nasal carriage of MDRSA were also
      determined. RESULTS: A total of 92 (26.3%) S. aureus isolates were obtained, of
      which 33 (35.9%) were MRSA and 27 (29.3%) were MDRSA. Of MRSA strains, 19 (70.4%)
      were MDRSA. S. aureus isolates showed 52.2% resistance to cephalothin, 33.7% to
      co-trimoxazole, 26.1% to clindamycin, 26.1% to ciprofloxacin, 4.3% to vancomycin,
      and 35.9% to oxacillin. The risk factors for nasal carriage of MDRSA were
      antibiotic usage during the last three months (P = 0.006), family size of more
      than four members (P = 0.044), and parental smoking (P = 0.045). CONCLUSIONS:
      MDRSA was not uncommon among healthy children in Kashan and prevention of its
      spread in the population is judicious.

PMID- 25593735
TI  - Overview of avicenna (ibn sina) opinion on stomach swelling.

PMID- 25593736
TI  - Effectiveness of oral ketamine, midazolam, and atropine cocktail versus oral
      diphenhydramine for pediatric sedation in the emergency department.
AB  - BACKGROUND: Sedation is a condition of reduced level of consciousness (LOC) for a
      patient that is created to decrease irritability, anxiety, and restlessness.
      OBJECTIVES: In this study, we compared the sedative effect of oral administration
      of ketamine, midazolam, and atropine cocktail with diphenhydramine in the
      referent children to the emergency department. PATIENTS AND METHODS: Based on the
      double-blind randomized clinical trial in this investigation, 80 children, who
      needed to repair their wounds with suture were randomly divided into two groups:
      group 1 and group 2, who have received oral diphenhydramine and oral ketamine,
      midazolam, and atropine cocktail, respectively. Behavioral changes were collected
      and recorded before, during intervention and two weeks after intervention.
      Statistical data were analyzed by SPSS-16 software and chi-square and Mann
      Whitney U tests were employed to study the relations among variables. P < 0.05
      was considered statistically significant. RESULTS: There was no significant
      difference between two groups in terms of drug acceptance and anxiety degree in
      children before intervention. Group 2 had achieved better and deeper sedation
      than group 1 during 45-minute post-medication (P < 0.05, P = 0.01). Regarding
      pediatric general behavior such as crying or interruptive moves, there was also a
      significant statistical difference between group 2 and group 1 (P = 0.009) based
      on Houpt Classification. The mean recovery times in groups 1 and 2 were 34.37 +/-
      14.23 min and 27.25 +/- 5.14 min, respectively (P = 0.003). In terms of
      behavioral changes, the rate of cumulative frequency was computed for behavioral
      changes two weeks after the discharge from emergency department in which there
      were less behavioral changes in group 2 than in group 1 (P = 0.04). CONCLUSIONS:
      Oral administration of ketamine, midazolam, and atropine cocktail induces better
      sedation than diphenhydramine with respect to its limited mood changes in
      children, who need a medical procedure at emergency department.

PMID- 25593737
TI  - Effect of therapeutic dose of vitamin d on serum adiponectin and glycemia in
      vitamin d-insufficient or deficient type 2 diabetic patients.
AB  - BACKGROUND: Lower vitamin D status has been reported in diabetic patients. Serum
      25-hydroxyvitamin D and adiponectin were inversely associated with type 2
      diabetes and insulin resistance. Vitamin D may involve in regulation of the
      adiponectin levels, which is directly related to insulin sensitivity. OBJECTIVES:
      The aim of this study was to investigate the effect of therapeutic dose of
      vitamin D on serum adiponectin and insulin resistance in vitamin D-insufficient
      or deficient type 2 diabetic patients. MATERIALS AND METHODS: This double-blind,
      randomized, clinical trial was conducted on 81 type 2 diabetic patients with
      vitamin D level of 10-30 ng/mL. Intervention was 50000 IU vitamin D or placebo
      once a week for 8 weeks. At the beginning and end of the study, blood samples
      were collected after 12 hours of fasting and serum glucose, insulin, 25
      hydroxyvitamin D, and adiponectin were measured. Insulin resistance was
      calculated by homeostasis model assessment (HOMA-IR). RESULTS: After 8-week
      intervention, serum 25-hydroxyvitamin D significantly increased and reached the
      normal levels in patients receiving vitamin D (P < 0.001) and the levels of
      fasting serum glucose, insulin, and HOMA-IR were significantly decreased (P =
      0.04, 0.02 and 0.007, respectively). No significant changes were observed in
      these levels in the placebo group. Significant differences were observed in mean
      changes in the above-mentioned variables between the two groups (P = 0.01, 0.04
      and 0.006, respectively). No significant changes were found in serum adiponectin
      in the vitamin D and placebo groups (P = 0.83). CONCLUSIONS: Therapeutic dose of
      vitamin D can improve vitamin D status and glycemic indicators. But it seems that
      an 8-week intervention period was not sufficient to reveal the possible effects
      of vitamin D on serum adiponectin levels.

PMID- 25593738
TI  - Investigating happiness and its related factors in married women referred to
      health centers of shahroud city.
AB  - BACKGROUND: Happiness is one of the most important factors affecting women's
      mental health. Several factors contribute to happiness in different societies.
      OBJECTIVES: The aim of this study was to investigate the level of happiness in
      married women and its related factors. MATERIALS AND METHODS: This was a cross
      sectional study with stratified sampling proportional to different age groups of
      married women in selected health centers (based on socioeconomic status).
      Subjects were 379 married women. The Oxford Happiness Inventory (scale: 0-87) was
      used to measure happiness. The Enrich Marital Satisfaction Inventory including 47
      questions (scale: 47-235) and demographic information questionnaires were also
      used. Descriptive statistics, correlation, T-test, One-way ANOVA and Regression
      were used to analyze data. RESULTS: The mean of happiness was 45.11 +/- 14.40.
      Marital satisfaction was 164.68 +/- 28.33 and 64% of the participants had a
      relative marital satisfaction. Univariate analysis of happiness showed
      significant effects of husband and wife education, husband job, economic status,
      stress in past six months, marital satisfaction and having social activates, but
      was not statistically significant for other factors (P < 0.05). Adjusting for the
      confounding effect of other variables, multiple linear regressions showed
      significant association of happiness with marital satisfaction, economic status
      and social activity. CONCLUSIONS: Regarding lower level of happiness of married
      women in Shahroud comparing to some other studies in Iran and abroad, leisure
      time programs, training life skills especially stress management skills,
      increasing marital satisfaction and improving economic status should be
      considered.

PMID- 25593739
TI  - Iatrogenic submandibular duct rupture complicating sialography: a case report.
AB  - INTRODUCTION: Sialolithiasis is the most common disease of salivary glands.
      Sialography is particularly important for the assessment of the outflow tract and
      in diagnosing obstructive salivary gland lesions including calculi. CASE
      PRESENTATION: We report on a 38-year-old female with sialolithiasis whom had
      Wharton's duct perforation, complicating the sialography. She was treated
      conservatively with a course of co-amoxiclav, oral prednisolone for three days
      and pain-killers. The patient was clinically well on follow-up reassessments at
      the end of the first week and three weeks post procedure. CONCLUSIONS:
      Perforation of salivary duct complicating the sialography is rare. Awareness of
      this potential complication and utilizing a good sialography technique need to be
      advocated amongst radiologists. Response to treatment by conservative management
      is preferred as illustrated in this case.

PMID- 25593741
TI  - Mechanisms and etiologies of thrombocytopenia in the intensive care unit: impact
      of extensive investigations.
AB  - BACKGROUND: Thrombocytopenia is common in the intensive care unit. Potential
      mechanisms and etiologies behind this phenomenon are multiple and often
      entangled. We assessed the effect of a systematic approach, using routinely
      available tests, on the proportion of patients in whom the mechanism (primary
      objective) and etiology (secondary objective) of thrombocytopenia in a mixed
      intensive care unit (ICU) could be identified. METHODS: Before-and-after study of
      all patients with thrombocytopenia was used. 'Before' group had no intervention.
      New standard operating procedures for thrombocytopenia management were
      introduced. In the 'After' group, bone marrow aspiration; determination of
      fibrinogen dosage, prothrombin time, factor V, D-dimers; assay of fibrin
      monomers, ferritin, triglycerides, lactic acid dehydrogenase, aspartate
      transaminase, alanine aminotransferase, vitamin B12, folates, reticulocytes,
      haptoglobin, and bilirubin were performed. RESULTS: In the Before group (n = 20),
      the mechanism (central, peripheral, or mixed) was identified in 10 % versus 83%
      in After group (n = 23) (p < 0.001) (48% peripheral, 35% mixed). Before
      intervention, >=1 etiology was identified in 15% versus 95.7% in the After group
      (p < 0.001). CONCLUSIONS: Systematic and extensive investigation using routine
      tests highlights the mechanisms and etiology of thrombocytopenia in most cases.

PMID- 25593740
TI  - Design and implementation of the START (STem cells for ARDS Treatment) trial, a
      phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of
      moderate-severe acute respiratory distress syndrome.
AB  - BACKGROUND: Despite advances in supportive care, moderate-severe acute
      respiratory distress syndrome (ARDS) is associated with high mortality rates, and
      novel therapies to treat this condition are needed. Compelling pre-clinical data
      from mouse, rat, sheep and ex vivo perfused human lung models support the use of
      human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for
      the early treatment of ARDS. METHODS: This article describes the study design and
      challenges encountered during the implementation and phase 1 component of the
      START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow
      derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is
      planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or
      placebo in a 2:1 ratio). RESULTS: This report describes study design features
      that are unique to a phase 1 trial in critically ill subjects and the specific
      challenges of implementation of a cell-based therapy trial in the ICU.
      CONCLUSIONS: Experience gained during the design and implementation of the START
      study will be useful to investigators planning future phase 1 clinical trials
      based in the ICU, as well as trials of cell-based therapy for other acute
      illnesses. TRIAL REGISTRATION:  CLINICAL TRIALS REGISTRATION: NCT01775774 and
      NCT02097641.

PMID- 25593742
TI  - Duration of hemodynamic effects of crystalloids in patients with circulatory
      shock after initial resuscitation.
AB  - BACKGROUND: In the later stages of circulatory shock, monitoring should help to
      avoid fluid overload. In this setting, volume expansion is ideally indicated only
      for patients in whom the cardiac index (CI) is expected to increase. Crystalloids
      are usually the choice for fluid replacement. As previous studies evaluating the
      hemodynamic effect of crystalloids have not distinguished responders from non
      responders, the present study was designed to evaluate the duration of the
      hemodynamic effects of crystalloids according to the fluid responsiveness status.
      METHODS: This is a prospective observational study conducted after the initial
      resuscitation phase of circulatory shock (>6 h vasopressor use). Critically ill,
      sedated adult patients monitored with a pulmonary artery catheter who received a
      fluid challenge with crystalloids (500 mL infused over 30 min) were included.
      Hemodynamic variables were measured at baseline (T0) and at 30 min (T1), 60 min
      (T2), and 90 min (T3) after a fluid bolus, totaling 90 min of observation. The
      patients were analyzed according to their fluid responsiveness status (responders
      with CI increase >15% and non-responders <=15% at T1). The data were analyzed by
      repeated measures of analysis of variance. RESULTS: Twenty patients were
      included, 14 of whom had septic shock. Overall, volume expansion significantly
      increased the CI: 3.03 +/- 0.64 L/min/m(2) to 3.58 +/- 0.66 L/min/m(2) (p <
      0.05). From this period, there was a progressive decrease: 3.23 +/- 0.65
      L/min/m(2) (p < 0.05, T2 versus T1) and 3.12 +/- 0.64 L/min/m(2) (p < 0.05,
      period T3 versus T1). Similar behavior was observed in responders (13 patients),
      2.84 +/- 0.61 L/min/m(2) to 3.57 +/- 0.65 L/min/m(2) (p < 0.05) with volume
      expansion, followed by a decrease, 3.19 +/- 0.69 L/min/m(2) (p < 0.05, T2 versus
      T1) and 3.06 +/- 0.70 L/min/m(2) (p < 0.05, T3 versus T1). Blood pressure and
      cardiac filling pressures also decreased significantly after T1 with similar
      findings in both responders and non-responders. CONCLUSIONS: The results suggest
      that volume expansion with crystalloids in patients with circulatory shock after
      the initial resuscitation has limited success, even in responders.

PMID- 25593743
TI  - Early-phase changes of extravascular lung water index as a prognostic indicator
      in acute respiratory distress syndrome patients.
AB  - BACKGROUND: The features of early-phase acute respiratory distress syndrome
      (ARDS) are leakage of fluid into the extravascular space and impairment of its
      reabsorption, resulting in extravascular lung water (EVLW) accumulation. The
      current study aimed to identify how the initial EVLW values and their change were
      associated with mortality. METHODS: This was a post hoc analysis of the PiCCO
      Pulmonary Edema Study, a multicenter prospective cohort study that included 23
      institutions. Single-indicator transpulmonary thermodilution-derived EVLW index
      (EVLWi) and conventional prognostic factors were prospectively collected over 48
      h after enrollment. Associations between 28-day mortality and each variable
      including initial (on day 0), mean, maximum, and Delta (subtracting day 2 from
      day 0) EVLWi were evaluated. RESULTS: We evaluated 192 ARDS patients (median age,
      69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score
      on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant
      differences were found in initial, mean, or maximum EVLWi, Delta-EVLWi was
      significantly higher (i.e., more reduction in EVLWi) in survivors than in non
      survivors (3.0 vs. -0.3 mL/kg, p = 0.006). Age, maximum, and Delta-SOFA scores
      and Delta-EVLW were the independent predictors for survival according to the Cox
      proportional hazard model. Patients with Delta-EVLWi > 2.8 had a significantly
      higher incidence of survival than those with Delta-EVLWi <= 2.8 (log-rank test,
      chi (2) = 7.08, p = 0.008). CONCLUSIONS: Decrease in EVLWi during the first 48 h
      of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be
      useful for understanding the pathophysiologic conditions in ARDS patients. A
      large multination confirmative trial is required.

PMID- 25593744
TI  - Pulmonary vascular dysfunction in ARDS.
AB  - Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar
      damage and is frequently complicated by pulmonary hypertension (PH). Multiple
      factors may contribute to the development of PH in this setting. In this review,
      we report the results of a systematic search of the available peer-reviewed
      literature for papers that measured indices of pulmonary haemodynamics in
      patients with ARDS and reported on mortality in the period 1977 to 2010. There
      were marked differences between studies, with some reporting strong associations
      between elevated pulmonary arterial pressure or elevated pulmonary vascular
      resistance and mortality, whereas others found no such association. In order to
      discuss the potential reasons for these discrepancies, we review the
      physiological concepts underlying the measurement of pulmonary haemodynamics and
      highlight key differences between the concepts of resistance in the pulmonary and
      systemic circulations. We consider the factors that influence pulmonary arterial
      pressure, both in normal lungs and in the presence of ARDS, including the
      important effects of mechanical ventilation. Pulmonary arterial pressure,
      pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone
      on the intrinsic properties of the pulmonary vascular bed but are also strongly
      influenced by cardiac output, airway pressures and lung volumes. The great
      variability in management strategies within and between studies means that no
      unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir
      Crit Care Med 182:1123-1128, 2010) have recently reported that elevated pulmonary
      vascular resistance (PVR) and TPG were independently associated with increased
      mortality in ARDS, in a large trial with protocol-defined management strategies
      and using lung-protective ventilation. We then considered the existing literature
      to determine whether the relationship between PVR/TPG and outcome might be
      causal. Although we could identify potential mechanisms for such a link, the
      existing evidence does not allow firm conclusions to be drawn. Nonetheless,
      abnormally elevated PVR/TPG may provide a useful index of disease severity and
      progression. Further studies are required to understand the role and importance
      of pulmonary vascular dysfunction in ARDS in the era of lung-protective
      ventilation. 

PMID- 25593745
TI  - High-flow nasal cannula: recommendations for daily practice in pediatrics.
AB  - High-flow nasal cannula (HFNC) is a relatively new device for respiratory
      support. In pediatrics, HFNC use continues to increase as the system is easily
      set up and is well tolerated by patients. The use of nasal cannula adapted to the
      infant's nares size to deliver heated and humidified gas at high flow rates has
      been associated with improvements in washout of nasopharyngeal dead space, lung
      mucociliary clearance, and oxygen delivery compared with other oxygen delivery
      systems. HFNC may also create positive pharyngeal pressure to reduce the work of
      breathing, which positions the device midway between classical oxygen delivery
      systems, like the high-concentration face mask and continuous positive airway
      pressure (CPAP) generators. Currently, most of the studies in the pediatric
      literature suggest the benefits of HFNC therapy only for moderately severe acute
      viral bronchiolitis. But, the experience with this device in neonatology and
      adult intensive care may broaden the pediatric indications to include weaning
      from invasive ventilation and acute asthma. As for any form of respiratory
      support, HFNC initiation in patients requires close monitoring, whether it be for
      pre- or inter-hospital transport or in the emergency department or the pediatric
      intensive care unit. 

PMID- 25593746
TI  - When to stop septic shock resuscitation: clues from a dynamic perfusion
      monitoring.
AB  - BACKGROUND: The decision of when to stop septic shock resuscitation is a critical
      but yet a relatively unexplored aspect of care. This is especially relevant since
      the risks of over-resuscitation with fluid overload or inotropes have been
      highlighted in recent years. A recent guideline has proposed normalization of
      central venous oxygen saturation and/or lactate as therapeutic end-points,
      assuming that these variables are equivalent or interchangeable. However, since
      the physiological determinants of both are totally different, it is legitimate to
      challenge the rationale of this proposal. We designed this study to gain more
      insights into the most appropriate resuscitation goal from a dynamic point of
      view. Our objective was to compare the normalization rates of these and other
      potential perfusion-related targets in a cohort of septic shock survivors.
      METHODS: We designed a prospective, observational clinical study. One hundred and
      four septic shock patients with hyperlactatemia were included and followed until
      hospital discharge. The 84 hospital-survivors were kept for final analysis. A
      multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU
      treatment. RESULTS: Some variables such as central venous oxygen saturation,
      central venous-arterial pCO2 gradient, and capillary refill time were already
      normal in more than 70% of survivors at 6 h. Lactate presented a much slower
      normalization rate decreasing significantly at 6 h compared to that of baseline
      (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of
      patients achieving normality at 24 h. Sublingual microcirculatory variables
      exhibited the slowest recovery rate with persistent derangements still present in
      almost 80% of patients at 24 h. CONCLUSIONS: Perfusion-related variables exhibit
      very different normalization rates in septic shock survivors, most of them
      exhibiting a biphasic response with an initial rapid improvement, followed by a
      much slower trend thereafter. This fact should be taken into account to determine
      the most appropriate criteria to stop resuscitation opportunely and avoid the
      risk of over-resuscitation.

PMID- 25593747
TI  - Timing of (supplemental) parenteral nutrition in critically ill patients: a
      systematic review.
AB  - Supplemental parenteral nutrition (SPN) is used in a step-up approach when full
      enteral support is contraindicated or fails to reach caloric targets. Recent
      nutrition guidelines present divergent advices regarding timing of SPN in
      critically ill patients ranging from early SPN (<48 h after admission; EPN) to
      postponing initiation of SPN until day 8 after Intensive Care Unit (ICU)
      admission (LPN). This systematic review summarizes results of prospective studies
      among adult ICU patients addressing the best timing of (supplemental) parenteral
      nutrition (S)PN. A structured PubMed search was conducted to identify eligible
      articles. Articles were screened and selected using predetermined criteria and
      appraised for relevance and validity. After critical appraisal, four randomized
      controlled trials (RCTs) and two prospective observational studies remained. One
      RCT found a higher percentage of alive discharge from the ICU at day 8 in the LPN
      group compared to EPN group (p = 0.007) but no differences in ICU and in-hospital
      mortality. None of the other RCTs found differences in ICU or in-hospital
      mortality rates. Contradicting or divergent results on other secondary outcomes
      were found for ICU length of stay, hospital length of stay, infection rates,
      nutrition targets, duration of mechanical ventilation, glucose control, duration
      of renal replacement therapy, muscle wasting and fat loss. Although the
      heterogeneity in quality and design of relevant studies precludes firm
      conclusions, it is reasonable to assume that in adult critically ill patients,
      there are no clinically relevant benefits of EPN compared with LPN with respect
      to morbidity or mortality end points, when full enteral support is
      contraindicated or fails to reach caloric targets. However, considering that
      infectious morbidity and resolution of organ failure may be negatively affected
      through mechanisms not yet clearly understood and acquisition costs of parenteral
      nutrition are higher, the early administration of parenteral nutrition cannot be
      recommended. 

PMID- 25593748
TI  - Systemic corticosteroids in acute exacerbation of COPD: a meta-analysis of
      controlled studies with emphasis on ICU patients.
AB  - Guidelines on systemic corticosteroids in chronic obstructive pulmonary disease
      (COPD) exacerbation rely on studies that excluded patients requiring ventilatory
      support. Recent publication of studies including ICU patients allows estimation
      of the level of evidence overall and in patients admitted to the ICU. We included
      RCTs evaluating the efficacy and safety of systemic corticosteroids in COPD
      exacerbation, compared to placebo or standard treatment. The effect size on
      treatment success was computed by a random effects model overall and in subgroups
      of non-ICU and ICU patients. Effects on mortality and on the rate of adverse
      effects of corticosteroids were also computed. Twelve RCTs (including 1,331
      patients) were included. Pooled analysis showed a statistically significant
      increase in the treatment success rate when using systemic corticosteroids: odds
      ratio (OR) = 1.72, 95% confidence interval (CI) = 1.15 to 2.57; p = 0.01.
      Subgroup analysis showed different patterns of effect in ICU and non-ICU
      subpopulations: a non-significant difference of effect in the subgroup of ICU
      patients (OR = 1.34, 95% CI = 0.61 to 2.95; p = 0.46), whereas in the non-ICU
      patients, the effect was significant (OR = 1.87, 95% CI = 1.18 to 2.99; p = 0.01;
      p for interaction = 0.72). Among ICU patients, there was no difference in the
      success whether patients were ventilated with tracheal intubation (OR = 1.85, 95%
      CI = 0.14 to 23.34; p = 0.63) or with non-invasive ventilation (OR = 4.88, 95% CI
      = 0.31 to 75.81; p = 0.25). Overall, there was no difference in the mortality
      rate between the steroid-treated group and controls: OR = 1.07, 95% CI = 0.67 to
      1.71; p = 0.77. The rate of adverse events increased significantly with
      corticosteroid administration (OR = 2.36, 95% CI = 1.67 to 3.33; p < 0.0001). In
      particular, treatment with systemic corticosteroids significantly increased the
      risk of hyperglycemic episodes requiring initiation or alteration of insulin
      therapy (OR = 2.96, 95% CI = 1.69 to 5; p < 0.0001). We found corticosteroids to
      be beneficial in the whole population (non-critically ill and critically ill
      patients) in terms of treatment success rate. However, subgroup analysis showed
      that this effect of corticosteroids was only observed in non-critically ill
      patients whereas critically ill patients derived no benefit from systemic
      corticosteroids regardless of the chosen ventilatory mode (invasive or non
      invasive ventilation). Further analyses showed no effect on mortality of
      corticosteroids, but higher side effects, such as hyperglycemic episodes
      requiring the initiation or alteration of insulin therapy. 

PMID- 25593749
TI  - A ventilator strategy combining low tidal volume ventilation, recruitment
      maneuvers, and high positive end-expiratory pressure does not increase sedative,
      opioid, or neuromuscular blocker use in adults with acute respiratory distress
      syndrome and may improve patient comfort.
AB  - BACKGROUND: The Lung Open Ventilation Study (LOV Study) compared a low tidal
      volume strategy with an experimental strategy combining low tidal volume, lung
      recruitment maneuvers, and higher plateau and positive end-expiratory pressures
      (PEEP) in adults with acute respiratory distress syndrome (ARDS). Herein, we
      compared sedative, opioid, and neuromuscular blocker (NMB) use among patients
      managed with the intervention and control strategies and clinicians' assessment
      of comfort in both groups. METHODS: This was an observational substudy of the LOV
      Study, a randomized trial conducted in 30 intensive care units in Canada,
      Australia, and Saudi Arabia. In 16 centers, we recorded daily doses of sedatives,
      opioids, and NMBs and surveyed bedside clinicians about their own comfort with
      the assigned ventilator strategy and their perceptions of patient comfort. We
      compared characteristics and outcomes of patients who did and did not receive
      NMBs. RESULTS: Study groups received similar sedative, opioid, and NMB dosing on
      days 1, 3, and 7. Patient comfort as assessed by clinicians was not different in
      the two groups: 93% perceived patients had no/minimal discomfort. In addition,
      92% of clinicians were comfortable with the assigned ventilation strategy without
      significant differences between the two groups. When clinicians expressed
      discomfort, more expressed discomfort about PEEP levels in the intervention vs
      control group (2.9% vs 0.7%, P <0.0001), and more perceived patient discomfort
      among controls (6.0% vs 4.3%, P = 0.049). On multivariable analysis, the
      strongest associations with NMB use were higher plateau pressure (hazard ratio
      (HR) 1.15; 95% confidence interval (CI) 1.07 to 1.23; P = 0.0002) and higher
      daily sedative dose (HR 1.03; 95% CI 1.02 to 1.05; P <0.0001). Patients receiving
      NMBs had more barotrauma, longer durations of mechanical ventilation and hospital
      stay, and higher mortality. CONCLUSIONS: In the LOV Study, high PEEP, low tidal
      volume ventilation did not increase sedative, opioid, or NMB doses in adults with
      ARDS, compared with a lower PEEP strategy, and appeared at least as comfortable
      for patients. NMB use may reflect worse lung injury, as these patients had more
      barotrauma, longer durations of ventilation, and higher mortality. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier NCT00182195.

PMID- 25593750
TI  - Healthcare-associated bloodstream infections in critically ill patients:
      descriptive cross-sectional database study evaluating concordance with clinical
      site isolates.
AB  - BACKGROUND: Healthcare-associated bloodstream infections are related to both
      increased antibiotic use and risk of adverse outcomes. An in-depth understanding
      of their epidemiology is essential to reduce occurrence and to improve outcomes
      by targeted prevention strategies. The objectives of the study were to determine
      the epidemiology, source and concordance of healthcare-associated bloodstream
      infections with clinical site isolates. METHODS: We conducted a descriptive cross
      sectional study in critically ill adults admitted to a tertiary semi-closed
      intensive care unit in England to determine the epidemiology, source and
      concordance of healthcare-associated bloodstream infections with clinical site
      isolates. All nosocomial positive blood cultures over a 4-year study period were
      identified. Pathogens detected and concordances with clinical site are reported
      as proportions. RESULTS: Contaminant pathogens accounted for half of the
      isolates. The most common non-contaminant pathogens cultured were Pseudomonas
      spp. (8.0%), Enterococcus spp. (7.3%) and Escherichia coli (5.6%). Central venous
      catheter-linked bloodstream infections represent only 6.0% of the positive blood
      cultures. Excluding contaminants and central venous line infections, in only
      39.5% of the bloodstream infections could a concordant clinical site source be
      identified, the respiratory and urinary tracts being the most common.
      CONCLUSIONS: Clinical practice should focus on a) improving blood culture
      techniques to reduce detection of contaminant pathogens and b) ensuring paired
      clinical site cultures are performed alongside all blood cultures to better
      understand the epidemiology and potential implications of primary and secondary
      discordant health-care associated bloodstream infections.

PMID- 25593751
TI  - Multiplex PCR performed of bronchoalveolar lavage fluid increases pathogen
      identification rate in critically ill patients with pneumonia: a pilot study.
AB  - BACKGROUND: In critically ill patients with pneumonia, accurate microorganism
      identification allows appropriate antibiotic treatment. In patients undergoing
      bronchoalveolar lavage (BAL), direct examination of the fluid using Gram staining
      provides prompt information but pathogen identification accuracy is low. Culture
      of BAL fluid is actually the reference, but it is not available before 24 to 48
      h. In addition, pathogen identification rate observed with direct examination and
      culture is decreased when antibiotic therapy has been given prior to sampling. We
      therefore assessed, in critically ill patients with suspected pneumonia, the
      performance of a multiplex PCR (MPCR) to identify pathogens in BAL fluid. This
      study is a prospective pilot observation. METHODS: We used a MPCR detecting 20
      types of microorganisms. Direct examination, culture, and MPCR were performed on
      BAL fluid of critically ill patients with pneumonia suspicion. The final
      diagnosis of infective pneumonia was retained after the medical chart was
      reviewed by two experts. Pathogen identification rate of direct examination,
      culture, and MPCR in patients with confirmed pneumonia was compared. RESULTS:
      Among the 65 patients with pneumonia suspicion, the diagnosis of pneumonia was
      finally retained in 53 cases. Twenty nine (55%) were community-acquired pneumonia
      and 24 (45%) were hospital acquired. Pathogen identification rate with MPCR (66%)
      was greater than with culture (40%) and direct examination (23%) (p =0.01 and p
      <0.001, respectively). When considering only the microorganisms included in the
      MPCR panel, the pathogen identification rate provided by MPCR reached 82% and was
      still higher than with culture (35%, p <0.001) and direct examination (21%, p
      <0.001). Pathogen identification rate provided by MPCR was not modified in the
      case of previous antibiotic treatment (66% vs. 64%, NS) and was still better than
      with culture (23%, p <0.001). CONCLUSIONS: The results of this pilot study
      suggest that in critically ill patients, MPCR performed on BAL fluid could
      provide higher identification rate of pathogens involved in pneumonia than direct
      examination and culture, especially in patients having received antimicrobial
      treatment.

PMID- 25593752
TI  - Postpartum acute renal failure: a multicenter study of risk factors in patients
      admitted to ICU.
AB  - BACKGROUND: Even in developed countries, severe specific pregnancy complications
      may occur in the immediate postpartum period and require admission to the ICU.
      The characteristics and risk factors of acute renal failure (ARF) induced by
      these complications and their treatments are not well known. METHODS: We
      performed a retrospective multicenter study in three intensive care departments
      linked to level III maternity wards in the north of France. All patients admitted
      to ICU for postpartum complications over a 5-year period (2008 to 2012) were
      included. Clinical and biological data, delivery characteristics, type of
      complications, and treatments were compared by univariate and multivariate
      analyses according to the occurrence and severity of ARF. RESULTS: One hundred
      eighty-two patients admitted to ICU for postpartum complications were included in
      the study. Sixty-eight patients (37%) developed an ARF: 49 with a low or medium
      severity and 19 with a severe ARF requiring renal replacement therapy. Hemolysis,
      elevated liver enzyme, and low platelet count (HELLP) syndrome on its own (p =
      0.047) or combined with postpartum haemorrhage (p = 0.003), previous treatment by
      hyperoncotic albumin infusion (p = 0.001) and blockade of fibrinolysis by
      tranexamic acid (p = 0.03), was associated with secondary ARF. By multivariate
      analysis, the only independent factors were the association of HELLP syndrome
      with postpartum haemorrhage and the use of hyperoncotic albumin infusion.
      CONCLUSIONS: HELLP syndrome associated with postpartum haemorrhage induces a high
      risk of ARF in the complicated postpartum setting. A particular attention should
      be given to treatments that could worsen the kidney function in that situation.

PMID- 25593753
TI  - Involvement of ICU families in decisions: fine-tuning the partnership.
AB  - Families of patients are not simple visitors to the ICU. They have just been
      separated from a loved one, often someone they live with, either abruptly or, in
      nearly half the cases, because a chronic condition has suddenly worsened. They
      must cope with a serious illness of a loved one, while having to adapt to the
      unfamiliar and intimidating ICU environment. In many cases, the outcome of the
      critical illness is uncertain, a situation that causes considerable distress to
      the relatives. As shown by our research group and others, families exhibit
      symptoms of anxiety (70%) and depression (35%) in the first few days after
      admission, as well as symptoms of stress (33%) and difficulty understanding the
      information delivered by the healthcare staff (50%). Furthermore, relatives of
      patients who die in the ICU are at risk for psychiatric syndromes such as
      generalized anxiety, panic attacks, depression, and posttraumatic stress
      syndrome. In this setting of psychological distress, families are asked to
      consider sharing in healthcare decisions about their loved one in the ICU. This
      article aims to foster the debate about the shared decision-making process. We
      have three objectives: to transcend the overly simplistic position that opposes
      paternalism and autonomy, to build a view founded only on an evaluation of actual
      practice and experience in the field, and to keep the focus squarely on the
      patient. Families want information and communication time from the staff. Nurses
      and physicians need to understand that families can share in decisions only if
      the entire ICU staff actively promotes family involvement and, of course, if the
      family wants to participate in all or part of the decision-making process. 

PMID- 25593754
TI  - The diagnostic properties of frozen sections in suspected intracranial tumors: A
      study of 578 consecutive cases.
AB  - BACKGROUND: Intraoperative frozen section (FS) diagnostics is an important
      diagnostic tool in neurosurgery, but agreement with final histopathology
      diagnoses may vary. In the present study we assess the diagnostic properties of
      intraoperative FSs in suspected intracranial tumors. METHODS: Retrospective
      single-center review of consecutive patients with suspected intracranial brain
      tumors from January 2008 to December 2012. We included all cases were both an
      intraoperative FS and a formalin-fixed paraffin-embedded (FFPE) section had been
      acquired. Agreement with final diagnosis, sensitivity, specificity, and
      predictive values were explored. Time between date of surgery and first final
      diagnosis based on FFPE section, whether the patients had undergone previous
      brain surgery and/or prior cerebral radiotherapy were also registered. RESULTS:
      Agreement between FS diagnoses and final FFPE section diagnoses was seen in
      504/558 (90.3%), while there was lack of agreement in 54/558 (9.7%). In 20 cases,
      agreement was not classifiable. Agreement was lower in low-grade gliomas (82.5%)
      than in high-grade gliomas (93.2%). Agreement between FS and FFPE was
      significantly higher in primary operations (92.1%) than in re-do operations
      (81.5%) (P = 0.001). Sensitivity of FS ranged from 30.8% in lymphomas to 94.6% in
      meningiomas. CONCLUSIONS: Intraoperative FS diagnoses demonstrate high diagnostic
      accuracy. However, agreement varies among histopathological entities and is lower
      in low-grade tumors than in high-grade tumors. Sensitivity for diagnosing CNS
      lymphomas is low. A variable degree of reservation is always necessary when
      interpreting and communicating FS diagnoses.

PMID- 25593756
TI  - Transfrontal sinus approach for an anterior cranial fossa, ethmoidal, dural
      arteriovenous fistula.
AB  - BACKGROUND: Ethmoidal dural arteriovenous fistulas (eDAVFs) are usually
      approached via a pterional or a frontal craniotomy. A more direct route to the
      fistula is possible through a purely transfrontal sinus approach. The aim of this
      report is to illustrate the interest of transsinus frontal approach for eDAVFs.
      CASE DESCRIPTION: The transfrontal sinus approach is described and illustrated in
      a case of an ethmoidal arteriovenous fistula. This approach is the most direct
      when treating an eDAVF surgically, allowing preserving neural structures with
      minimal to no brain manipulation. CONCLUSION: For eDAVFs, the purely transfrontal
      sinus approach is highly worth considering in cases of large frontal sinuses.

PMID- 25593755
TI  - Two alternative dural sealing techniques in posterior fossa surgery: (Polylactide
      co-glycolide) self-adhesive resorbable membrane versus polyethylene glycol
      hydrogel.
AB  - BACKGROUND: Post-operative cerebrospinal fluid (CSF) leak in posterior fossa
      surgery remains a significant source of morbidity. TissuePatchDural (TPD), a
      novel impermeable adhesive membrane, was used to reinforce dural closure. A
      comparison with one of the most commonly used dural sealing devices, DuraSeal,
      has been made. METHODS: A retrospective, single-center study was conducted on 161
      patients who underwent elective posterior fossa surgery. On surgeon's opinion,
      when a primary watertight closure was not possible, they received TPD or DuraSeal
      to reinforce dural closure. RESULTS: Out of 161 patients analyzed, 115 were
      treated with TPD and 46 with DuraSeal. The post-operative leaks related purely to
      TPD or DuraSeal failure were recognized in 3 (2.6%) and 5 (10.86%) cases,
      respectively (P = 0.015). The presence of pre- and post-operative risk factors
      was associated with an increased incidence of CSF leak in both groups. TPD showed
      a better control in patients without these risk factors (P = 0.08). The incidence
      of CSF leak in patients who underwent posterior fossa surgery by craniectomy was
      statistically lower in TPD group compared to DuraSeal group (3.22% vs 17.8%,
      respectively; P = 0.008). CONCLUSIONS: TPD seems to be a safe tool for use as an
      adjunct to standard dural closure in posterior fossa surgery, particularly in
      patients without pre- or post-oper ative risk factors, in those who did not
      develop hydrocephalus, and who underwent craniectomy. The CSF leak rate in TPD
      group was found to be lower or within the range of the more advanced alternative
      dural closure strategies, including polyethylene glycol (PEG)-based sealant.

PMID- 25593757
TI  - Evaluation of a novel phantom-based neurosurgical training system.
AB  - BACKGROUND: The complexity of neurosurgical interventions demands innovative
      training solutions and standardized evaluation methods that in recent times have
      been the object of increased research interest. The objective is to establish an
      education curriculum on a phantom-based training system incorporating theoretical
      and practical components for important aspects of brain tumor surgery. METHODS:
      Training covers surgical planning of the optimal access path based on real
      patient data, setup of the navigation system including phantom registration and
      navigated craniotomy with real instruments. Nine residents from different
      education levels carried out three simulations on different data sets with
      varying tumor locations. Trainings were evaluated by a specialist using a uniform
      score system assessing tumor identification, registration accuracy, injured
      structures, planning and execution accuracy, tumor accessibility and required
      time. RESULTS: Average scores improved from 16.9 to 20.4 between first and third
      training. Average time to craniotomy improved from 28.97 to 21.07 min, average
      time to suture improved from 37.83 to 27.47 min. Significant correlations were
      found between time to craniotomy and number of training (P < 0.05), between time
      to suture and number of training (P < 0.05) as well as between score and number
      of training (P < 0.01). CONCLUSION: The training system is evaluated to be a
      suitable training tool for residents to become familiar with the complex
      procedures of autonomous neurosurgical planning and conducting of craniotomies in
      tumor surgeries. Becoming more confident is supposed to result in less error
      prone and faster operation procedures and thus is a benefit for both physicians
      and patients.

PMID- 25593758
TI  - Comprehensive management of frontal and cerebellar tumor patients with
      personality changes and suicidal tendencies.
AB  - BACKGROUND: Brain tumor patients have a tendency to suffer from psychiatric
      disturbances. One of the most frequent disturbance experienced by frontal area
      tumor patients are personality changes. CASE DESCRIPTION: In this paper, the
      authors report a 28-year-old male patient who presented with headache and
      personality changes, with no other neurological disturbance. The patient became
      increasingly pensive and apathetic with frontal and cerebellopontine angle tumor.
      The diagnosis is based on computed tomography scanning images, and
      histopathological examination of the excised tumor results in meningioma.
      CONCLUSION: Before the operation was performed, the patient suffered from
      personality changes and suicidal tendencies. After the operation, the patient's
      suicidal tendency was gone, but the personality changes still persist. For this
      reason, a comprehensive management of the patient is required, including
      postoperative pharmacological and psychological treatment.

PMID- 25593760
TI  - A regional focus for solving the skills-jobs mismatch.

PMID- 25593759
TI  - Hydrocephalus in children less than 1 year of age in northern Mozambique.
AB  - BACKGROUND: In developed countries, the incidence of neonatal hydrocephalus
      ranges from 3 to 5 cases per 1000 live births, but little is known about the
      frequency of hydrocephalus in Africa. In Mozambique, there is no primary
      information related to this disorder, but using the above data, the expected
      incidence of neonatal hydrocephalus would range from 2900 to 4800 cases per year.
      METHODS: This study is based on 122 children younger than 1 year with neonatal
      hydrocephalus, followed up between January 2010 and December 2012, their origin
      and treatment, and aims to evaluate difficulties with diagnosis, treatment, and
      follow-up in northern Mozambique. RESULTS: Identified cases were mainly less than
      6 months old (77%), with severe macrocephaly and the classic stigmata of this
      condition. A high rate of follow-up loss (44.3%) was detected, particularly among
      children from more distant locations. Our findings contrast with the expected
      1000-1700 cases that would occur in the area during the study period, being
      considerably lower. CONCLUSIONS: Hydrocephalus is a serious problem in sub
      Saharan Africa, whose effects can be minimized by a better organization of the
      health system in hydrocephalus prevention, referral, and follow-up. New
      management alternatives to provide treatment to more children with this disorder
      and reduction of the follow-up difficulties caused due to geographical reasons
      for the children undergoing treatment are essential.

PMID- 25593761
TI  - Sudden unexpected nocturnal death in Chiari type 1 malformation and potential
      role of opioid analgesics.

PMID- 25593762
TI  - Comparison of outcomes and utilization of extracranial-intracranial bypass versus
      intracranial stenting for intracranial stenosis.
AB  - BACKGROUND: Extracranial-intracranial (EC-IC) bypass and intracranial stenting
      (ICS) are both revascularization procedures that have emerged as treatment
      options for intracranial atherosclerotic disease (ICAD). This study describes and
      compares recent trends in utilization and outcomes of intracranial
      revascularization procedures in the United States using a population-based
      cohort. It also investigates the association of ICS and EC-IC bypass with
      periprocedural morbidity and mortality, unfavorable discharge status, length of
      stay (LOS), and total hospital charges. METHODS: The National Inpatient Sample
      (NIS) was queried for patients with ICAD who underwent EC-IC bypass or ICS during
      the years 2004-2010. Patient characteristics, demographics, perioperative
      complications, outcomes, and discharge data were collected. RESULTS: There were
      627 patients who underwent ICS and 249 patients who underwent EC-IC bypass.
      Patients who underwent ICS were significantly older (P < 0.001) with more
      comorbidities (P = 0.027) than those who underwent EC-IC bypass. Patients who
      underwent EC-IC bypass experienced higher rates of postprocedure stroke (P =
      0.014), but those who underwent ICS experienced higher rates of death (P =
      0.006). Among asymptomatic patients, the rates of postprocedure stroke (P =
      0.341) and death (P = 0.887) were similar between patients who underwent ICS and
      those who underwent EC-IC bypass. Among symptomatic patients, however, there was
      a higher rate of postprocedure stroke in patients who underwent EC-IC bypass (P <
      0.001) and a higher rate of death among patients who underwent ICS (P = 0.015).
      CONCLUSION: The ideal management of patients with ICAD cannot yet be defined.
      Although much data from randomized and prospective trials on revascularization
      have been collected, many questions remain unanswered. There still remain cohorts
      of patients, specifically patients who have failed aggressive medical management,
      where not enough evidence is available to dictate decision-making. In order to
      further elucidate the safety and efficacy of these intracranial revascularization
      procedures, further clinical trials are needed.

PMID- 25593764
TI  - A rare case of thoracic extradural thrombosed primary cavernous haemangioma in a
      relatively asymptomatic patient.

PMID- 25593765
TI  - Physician shortage and the future of medicine.

PMID- 25593766
TI  - Manual aspiration thrombectomy for basilar infarction in the setting of a
      persistent primitive hypoglossal artery: Case report and review of the
      literature.
AB  - BACKGROUND: Persistent primitive hypoglossal artery (PPHA), a remnant of
      embryonal circulation, is a rare variant of the posterior cerebral circulation.
      Seven prior cases of posterior circulation stroke in the setting of PPHA have
      been described in the literature, with all but one case being attributable to
      atherosclerotic embolization from the internal carotid artery (ICA) through the
      PPHA. CASE DESCRIPTION: We report a unique case of a young male with a PPHA
      presenting with a "top of the basilar" syndrome following the repair of his
      atrial septal defect who underwent emergent revascularization via endovascular
      mechanical aspiration thrombectomy. The patient underwent a successful aspiration
      thrombectomy with significant improvement in his clinical exam. CONCLUSIONS:
      Considering the rarity of this persistent fetal anastamosis, it is important to
      be aware of the propensity for unusual presentations in the context of stroke,
      understand the management of the problem, and expeditiously treat the patient.

PMID- 25593763
TI  - Microsurgical treatment of large and giant tympanojugular paragangliomas.
AB  - BACKGROUND: Tympanojugular paragangliomas (TJPs) are benign, highly vascularized
      lesions located in the jugular foramen with frequent invasion to the temporal
      bone, the upper neck, and the posterior fossa cavity. Their natural history,
      surgical treatment, and outcome have been well addressed in the recent
      literature; however, there is no consensus regarding the optimal management while
      minimizing treatment-related morbidity. In this study, we assessed the
      interdisciplinary microsurgical treatment and outcome of large TJP collected at a
      single center. METHODS: Out of 54 patients with skull base paraganglioma, 14
      (25%) presented with large TJP (Fisch grade C and D). Posterior fossa involvement
      was present in 10 patients (Fisch D). Eleven patients presented with hearing
      loss, two patients with mild facial nerve palsy, and two patients with lower
      cranial nerve deficits. Two other patients with previous surgery presented with
      tumor regrowth. RESULTS: Preoperative embolization was performed in 13 cases.
      Radical tumor removal was possible in 10 patients. Hearing was preserved in four
      patients with normal preoperative audiogram. The facial nerve was preserved in
      all patients. Temporary facial nerve palsy occurred in two patients and resolved
      in long-term follow-up. In three patients, preexisting facial nerve palsy
      remained unchanged. Persistent vocal cord palsy was present in three patients and
      was treated with laryngoplasty. The global recovery based on the Karnofsky
      performance scale was 100% in 10 patients and 90% in 4 patients. CONCLUSION:
      Preoperative embolization and interdisciplinary microsurgical resection are the
      preferred treatment for selected patients due to high tumor control rates and
      good long-term results.

PMID- 25593767
TI  - Atypical Neurocytoma: Dilemma in diagnosis and management.
AB  - BACKGROUND: Central neurocytoma is an uncommon benign tumor of the central
      nervous system. A section of these tumors have unusual aggressiveness and are
      termed as "atypical central neurocytomas," the definition of which is debated.
      Many studies in the available literature define them as tumors with elevated MIB
      1 labeling index (MIB-1 LI) >2%, while some associate them with higher values of
      MIB-1 LI or those with histological atypical features. Newer parameters also have
      been identified and correlated with MIB-1 LI to differentiate atypical from
      benign neurocytoma cases. A recent analysis of the atypical neurocytoma cases
      with malignant behavior revealed their increased tendency of spread through the
      cerebrospinal fluid causing craniospinal axis dissemination. However, limited
      studies document the appropriate indications and usefulness of additional
      therapeutic modalities, such as upfront craniospinal irradiation (CSI) or
      adjuvant chemotherapy, in countering the aggressive behavior of such tumors. CASE
      DESCRIPTION: We present two such rare cases of atypical neurocytoma with elevated
      MIB-1 LI, of 3% and 4%, respectively, without histological atypia. Since there is
      insufficient evidence documenting advantages of any additional measures in the
      adjuvant management of atypical cases, both patients were treated with localized
      cranial radiotherapy alone, as per the evidence available in the literature
      currently. CONCLUSION: We propose that future studies must aptly redefine these
      atypical neurocytomas with malignant potential and provide guidance to identify
      aggressiveness of these tumors early in the course of management. Lastly, strong
      evidence to provide specific adjuvant therapy is also warranted.

PMID- 25593769
TI  - Commentary: Utility of the O-Arm in spinal surgery.
AB  - BACKGROUND: More studies report the intraoperative benefits vs. risks of
      utilizing the O-Arm in performing pedicle screw insertion in spinal surgery.
      METHODS/RESULTS: Several studies document the utility of CT-guided O-arm
      placement of pedicle/lateral mass screws. Singh et al. documented the efficacy of
      CT guided-O Arm placement of pedicle screws and lateral mass screws in the upper
      cervical spine.[4] Specifically, 10 patients with unstable hangman's fractures
      (ages 17-80) required 52 screws; C2 pedicle screws (20), C3 lateral mass screws
      (20), C4 lateral mass screws (12) and one C2 pedicle screw. Of these only 5% were
      misplaced, and none had new neuorlogical deficits. Kim et al. demonstrated the
      safety/efficacy of the CT/O-arm in minimally invasive spine surgery (MIS)
      (posterior percutaneous spinal fusions).[1] Of 290 pedicle screws, 280 (96.6%)
      were acceptably placed. Kotani et al. compared the placement of 222 pedicle
      screws (29 patients operated upon with CT-based navigation) vs. 416 screws (32
      having surgery using O-arm-based navigation); postoperative CT studies confirmed
      the accuracy of screw placement, and no significant differences in the frequency
      of grade 2-3 perforations between the two groups. Nelson et al. analyzed the
      radiation exposure delivered to the operating room staff utilizing C-arm
      fluoroscopy (C-arm), portable X-ray (XR) radiography, and portable cone-beam
      computed tomography (O-arm); the surgeon and assistant were exposed to higher
      levels of scatter radiation from the C-arm, with a 7.7-fold increase in radiation
      exposure on the tube vs. detector sides.[3]. CONCLUSION: There are several pros
      and a few cons (radiation dosage) for the use of the O-arm in spine surgery.

PMID- 25593770
TI  - K-Wire fracture during minimally invasive transforaminal lumbar interbody fusion:
      Report of six cases and recommendations for avoidance and management.
AB  - BACKGROUND: Although rare, minimally invasive spine techniques do have the risk
      of intraoperative device failure. Kirschner wire (K-wire) fractures during
      minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) have not been
      previously reported. This report focuses on the incidence of k-wire fractures
      following MI-TLIF and describes techniques to help avoid and treat these
      fractures when they occur. METHODS:  INCLUSION CRITERIA: (i) patients underwent
      1, 2, or 3 level MI-TLIF over a 10-year period and (ii) had a k-wire fracture
      leading to a retained fragment. Exclusion criteria included: >10 degrees  coronal
      curves, significant sagittal malalignment, infection, and preoperative
      instrumentation failure. RESULTS: Of 513 patients undergoing MI-TLIF, 6 (1.2%)
      sustained k-wire fracture (3 males, 3 females, mean age 43 +/- 13 years).
      Complications included k-wire fracture alone (4 patients), cerebrospinal fluid
      (CSF) leak (1 patient), and both ileus and revision for hardware removal (1
      patient). All six patients went home postoperatively. The mean follow-up duration
      was 27.7 +/- 37.4 months. All retained k-wire fragments were located in the
      vertebral bodies at the tip of the pedicle screws; none breached the anterior
      cortex of the vertebral bodies. None of the k-wires migrated at final follow-up
      7.8 years (93.7 months) postoperatively. Furthermore, no complications were
      attributed to retained k-wires. CONCLUSIONS: K-wire fractures during MI-TLIF are
      rare (incidence of 1.2%) and retained k-wire segments led to no postoperative
      complications (e.g. no migration).

PMID- 25593768
TI  - The pathophysiology underlying repetitive mild traumatic brain injury in a novel
      mouse model of chronic traumatic encephalopathy.
AB  - BACKGROUND: An animal model of chronic traumatic encephalopathy (CTE) is
      essential for further understanding the pathophysiological link between
      repetitive head injury and the development of chronic neurodegenerative disease.
      We previously described a model of repetitive mild traumatic brain injury (mTBI)
      in mice that encapsulates the neurobehavioral spectrum characteristic of patients
      with CTE. We aimed to study the pathophysiological mechanisms underlying this
      animal model. METHODS: Our previously described model allows for controlled,
      closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were
      divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI
      mice received six concussive impacts daily, for 7 days. Mice were then
      subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days,
      1 month, and 6 months after the last TBI received. Brain sections were
      immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for
      activated microglia, and AT8 for phosphorylated tau protein. RESULTS: Brains from
      single and repetitive mTBI mice lacked macroscopic tissue damage at all time
      points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and
      increased phospho-tau immunoreactivity that was present acutely and at 1 month,
      but was not persistent at 6 months. Repetitive mTBI resulted in a more marked
      neuroinflammatory response, with persistent and widespread astrogliosis and
      microglial activation, as well as significantly elevated phospho-tau
      immunoreactivity to 6-months. CONCLUSIONS: The neuropathological findings in this
      new model of repetitive mTBI resemble some of the histopathological hallmarks of
      CTE, including increased astrogliosis, microglial activation, and
      hyperphosphorylated tau protein accumulation.

PMID- 25593771
TI  - A blast from the past!: The value of adding single slice magnetic resonance
      myelography sequence to magnetic resonance imaging of the spine; a flashback to
      the conventional myelography of the past.
AB  - BACKGROUND: The study was undertaken to determine whether a single slice magnetic
      resonance (MR) myelogram sequence improves the interpretation and diagnostic
      yield for magnetic resonance imaging (MRI) of the spine. METHODS: A total of 100
      cases with positive findings were retrospectively reviewed. All patients had
      initial imaging with sagittal T1-weighted (T1-W) and T2-weighted (T2-W) scans,
      followed by axial T2-W images. Subsequently, a heavily T2-W single slice MR
      myelogram sequence was acquired in coronal and sagittal planes. The MR myelogram
      images were evaluated initially by a radiologist, and, further independently
      reviewed, by a neurologist, neurosurgeon, and spine surgeon. The utility of the
      MR myelogram in establishing the diagnosis was graded on a 4-point scale.
      RESULTS: Out of 100 cases, 53% showed degenerative spine or disc disease, 14%
      space occupying lesions, 13%, congenital lesions, 7% infection, and 7% other
      conditions. The MR myelogram contributed additional information in 50-74% cases.
      The intraclass correlation coefficient showed overall good agreement between
      observers in grading the utility of MR myelogram. CONCLUSION: Single slice MR
      myelography is noninvasive avoiding the complications associated with lumbar
      punctures/intrathecal contrast injections, while image acquisition takes only an
      added 6-8 s. Although MR myelogram has no value as a stand-alone sequence, its
      inherent advantage is that it completes the overview of the spinal pathology in
      entirety, and adds vital three-dimensional information in 50-74% of cases.

PMID- 25593772
TI  - Public awareness of the bone morphogenic protein controversy: Evidence from news
      publications.
AB  - BACKGROUND: Use of recombinant human bone morphogenic protein-2 (rhBMP-2) in
      spinal fusion has seen a tremendous increase. Public awareness of rhBMP-2 and its
      complications has not been assessed. The authors studied published news media
      articles to analyze information provided to the public on this bone graft
      substitute. METHODS: We utilized the academic database, LexisNexis, to locate
      newspaper articles published between January 2001 and July 2013. All articles
      were coded by a coder and reviewed by the principal investigator. RESULTS: The
      search identified 87 national and 99 local newspaper articles. Complications
      mentioned in national newspapers included cancer (24%), retrograde ejaculation
      (24%), and abnormal bone growth (14%). Local newspapers cited cancer (14%),
      inflammation (14%), and retrograde ejaculation (9.2%) most frequently. Fifty
      national (59%) and 35 local (54%) articles had no mention of complications.
      Sources of evidence cited by articles were (in order of frequency): Governmental
      agencies, medical research or published studies, healthcare personnel or
      patients, and companies or corporations. CONCLUSIONS: Only a small percentage of
      newspaper articles presented potential complications. Despite lack of clear
      scientific causal relationship between rhBMP-2 and cancer, this risk was
      disproportionately reported. Additionally, many did not cite scientific sources.
      Lack of reliable information available to the public reiterates the role of
      physicians in discussing risks and benefits BMP use in spinal surgery, assuring
      that patients are making informed decisions. Future news media articles should
      present risks in an impartial and evidence-based manner. Collaboration between
      advocacy groups, medical institutions, and media outlets would be beneficial in
      achieving this goal.

PMID- 25593773
TI  - Cervical laminoforaminotomy for radiculopathy: Symptomatic and functional
      outcomes in a large cohort with long-term follow-up.
AB  - BACKGROUND: The efficacy and safety of cervical laminoforaminotomy (FOR) in the
      treatment of cervical radiculopathy has been demonstrated in several series with
      follow-up less than a decade. However, there is little data analyzing the
      relative effectiveness of FOR for radiculopathy due to soft disc versus
      osteophyte disease. In the present study, we review our experience with FOR in a
      single-center cohort, with long-term follow-up. METHODS: We examined the charts
      of patients who underwent 1085 FORs between 1990 and 2009. A cohort of these
      patients participated in a telephone interview designed to assess improvement in
      symptoms and function. RESULTS: A total of 338 interviews were completed with a
      mean follow-up of 10 years. Approximately 90% of interviewees reported improved
      pain, weakness, or function following FOR. Ninety-three percent of patients were
      able to return to work after FOR. The overall complication rate was 3.3%, and the
      rate of recurrent radiculopathy requiring surgery was 6.2%. Soft disc subtypes
      compared to osteophyte disease by operative report were associated with improved
      symptoms (P < 0.05). The operative report of these pathologic subtypes was
      associated with the preoperative magnetic resonance imaging (MRI) interpretation
      (P < 0.001). CONCLUSIONS: These results suggest that FOR is a highly effective
      surgical treatment for cervical radiculopathy with a low incidence of
      complications. Radiculopathy due to soft disc subtypes may be associated with a
      better prognosis compared to osteophyte disease, although osteophyte disease
      remains an excellent indication for FOR.

PMID- 25593774
TI  - Anterior transarticular screw fixation as a conventional operation for rigid
      stabilization.
AB  - BACKGROUND: Anterior transarticular screw (ATS) fixation is a useful surgical
      option for atlantoaxial (AA) stabilization. This report presents a revised ATS
      method for AA fusion. METHODS: A 79-year-old male presented with AA instability
      attributed both to an old odontoid fracture and severe degeneration of the
      lateral atlantoaxial joints (LAAJs). ATS fixation was performed through the
      conventional anterior cervical approach. The longest screw trajectories were
      planned preoperatively using multiplanar reconstruction computed tomography (CT)
      scans, with entry points of the screws situated at the midpoint on the inferior
      border of the axial body. The surgical exposure was limited to opening at the
      entry points alone. Our retractor of choice was the Cusco speculum; it
      sufficiently secured space for utilizing the required instruments for screw
      placement while offering sufficient protection of soft tissues. Cannulated full
      threaded bicortical screws stabilized the LAAJs. Screw insertion required a
      significant amount of coronal angulation up to the superior articular process of
      the atlas under open-mouth and lateral fluoroscopy image guidance. After ATS
      fixation, bone grafting was performed between the posterior laminae of the axis
      and the atlas through a conventional posterior approach. RESULTS: Bony fusion
      between the atlas and the axis was confirmed radiographically. Arthrodesis of the
      LAAJs occurred despite no bone grafting. CONCLUSIONS: Rigid fixation of the LAAJs
      was obtained by our ATS technique, indicating that it is an alternative method
      for AA fixation when posterior rigid internal fixation is not applicable.

PMID- 25593775
TI  - Intraoperative neuro-monitoring corner editorial: The need for preoperative sep
      and mep baselines in spinal surgery: Why can't we and our monitoring colleagues
      get this right?
AB  - BACKGROUND: The majority of spinal surgeons now utilize intraoperative
      neurophysiological monitoring (IONM) during spinal procedures to limit the risk
      of inadvertent injury. Nevertheless, probably the most frequent error is the
      failure of the surgeon and IONM to obtain adequate preoperative baselines (e.g.
      before intubation or positioning). METHODS: Intraoperative neural monitoring
      should begin with the spinal surgeon, anesthesiologist, and monitoring
      technician/neurologist reviewing the patient's neurological deficits, the
      operative approach, the most anticipated risks and complications as well as the
      type of monitoring to be used (e.g. somatosensory evoked responses [SEP], motor
      evoked potential [MEP] monitoring, and electromyography [EMGs]). Baseline data
      should accurately reflect the preoperative status of the patient, and provide the
      appropriate data to be monitored and maintained throughout surgery. RESULTS:
      Significant but transient changes from the established preoperative baseline SEP
      and MEP often reflect alterations in the anesthetic technique (e.g.
      hypotension/hypoperfusion). However, when these changes persist, and
      resuscitative maneuvers have been exhausted (e.g. removing an oversized graft to
      avoid ischemia, utilizing total intravenous anesthesia [TIVA] correctly,
      reversing hypotension, changing the patient's cervical position, checking the
      electrode placement, checking the position of the limbs, and other factors),
      significant MEP/SEP changes may signal a major impending neural injury.
      CONCLUSION: IONM is only as good as how competently it is implemented by the
      technologist/neurologist, and understood by the surgeon and anesthesiologist. If
      any team member does not understand what and how the monitoring should be
      performed, then it becomes a useless adjunct to spinal surgery.

PMID- 25593776
TI  - Basic science and spine literature document bone morphogenetic protein increases
      cancer risk.
AB  - BACKGROUND: Increasingly, clinical articles document that bone morphogenetic
      protein (BMP/INFUSE: Medtronic, Memphis, TN, USA) and its derivatives utilized in
      spinal surgery increase the risk of developing cancer. However, there is also a
      large body of basic science articles that also document that various types of BMP
      and other members of the TGF-Beta (transforming growth factor beta) family
      promote the growth of different types of cancers. METHODS: This review looks at
      many clinical articles citing BMP/INFUSE's role, largely "off-label", in
      contributing to complications encountered during spinal surgery. Next, however,
      specific attention is given to the clinical and basic science literature
      regarding how BMP and its derivatives (e.g. members of the TGF-beta family) may
      also impact the development of breast and other cancers. RESULTS: Utilizing
      BMP/INFUSE in spine surgery increased the risk of cancers/new malignancy as
      documented in several studies. For example, Carragee et al. found that for single
      level instrumented posterolateral fusions (PLF) using high-dose rhBMP-2 (239
      patients) vs. autograft (control group; n = 224), the risks of new cancers at 2
      and 5 years postoperatively were increased. In laboratory studies, BMP's along
      with other members of the TGF-Beta family also modulated/contributed to the
      proliferation/differentiation of breast cancer (e.g. bone formation/turnover,
      breast cancer-related solid tumors, and metastases), lung, adrenal, and colon
      cancer. CONCLUSIONS: BMP/INFUSE when utilized clinically in spinal fusion surgery
      appears to promote cancer at higher rates than observed in the overall
      population. Furthermore, BMP and TGF-beta are correlated with increased cancer
      growth both in the clinic and the laboratory.

PMID- 25593777
TI  - Pedicle-sparing transforaminal thoracic spine wedge osteotomy for kyphosis
      correction.
AB  - BACKGROUND: Correction of a focal kyphotic deformity at times requires performing
      a pedicle subtraction osteotomy, which is accompanied by loss of pedicles as
      anchor points at the affected level in addition to significant blood loss. To
      help alleviate these two issues, a novel osteotomy technique for correction of
      kyphosis using a transforaminal approach to the thoracic vertebral body is
      described. METHODS: We describe a bilateral pedicle-sparing approach and
      demonstrate it in a patient with proximal junctional kyphosis. RESULTS: The
      proposed osteotomy resulted in a 28-degree Cobb angle improvement in the sagittal
      plane. CONCLUSION: The operation resulted in a similar degree of correction as a
      pedicle subtraction osteotomy, with the added benefit of maintaining the pedicles
      closest to the kyphotic deformity.

PMID- 25593778
TI  - The pathophysiology, classification, treatment, and prognosis of a spontaneous
      thoracic spinal cord herniation: A case study with literature review.
AB  - BACKGROUND: Spinal cord herniation was first described in 1974. It generally
      occurs in middle-aged adults in the thoracic spine. Symptoms typically include
      back pain and progressive paraparesis characterized by Brown-Sequard syndrome.
      Surgical reduction of the hernia improves the attendant symptoms and signs, even
      in patients with longstanding deficits. CASE DESCRIPTION: A 66-year-old female
      with back pain for 7 years, accompanied by paresthesias and a progressive
      paraparesis, underwent a thoracic MRI which documented a ventral spinal cord
      herniation at the T4 level. Following a laminectomy, with reduction of the hernia
      and ventral dural repair, the patient improved. CONCLUSION: Herniation of the
      thoracic cord, documented on MR, may produce symptomatic paraparesis which may
      resolve following laminectomy with ventral dural repair.

PMID- 25593779
TI  - Recurrent atlantoaxial synovial cyst resection via a navigation-guided, endoscope
      assisted posterior approach.
AB  - BACKGROUND: Atlantoaxial cysts are rare, and only 46 histologically confirmed
      cases have been reported. CASE DESCRIPTION: A 75-year-old male presented 2 years
      ago with headache, neck pain, loss of balance, and episodic dysphagia, for which
      he had undergone posterior cervical drainage of a left-sided atlantoaxial cyst.
      Although his original symptoms resolved, they recurred 2 years later and were
      correlated with an enhanced MR that showed a recurrent left C1-C2 synovial cyst
      causing marked cervical cord compression. It was successfully resected through a
      navigation-guided, endoscope-assisted posterior approach. The patient's
      symptoms/signs resolved completely, and he has remained symptom-free for over 30
      months postoperatively, with no evidence of recurrence on MR or craniocervical
      instability. CONCLUSIONS: A patient who successfully underwent resection of a
      recurrent synovial cervical cyst using a navigation-guided, endoscope-assisted
      posterior approach has been reported here.

PMID- 25593780
TI  - Commentary: Bone morphogenetic protein's contribution to pulmonary artery
      hypertension: Should this raise concern for patients undergoing spinal fusions
      with bone morphogenetic protein?
AB  - BACKGROUND: Congenital pulmonary artery hypertension (PAH) has been clinically
      correlated in 70-80% of cases with mutations at the bone morphogenetic protein
      receptor 2 (BMPR2) genetic site. However, there is also clinical and basic
      science/laboratory literature indicating a dose-response relationship between BMP
      signaling and the evolution of PAH (e.g., increased endothelial, smooth muscle,
      and progenitor cell production, with calcifications). METHODS: Clinical PAH,
      characterized by pulmonary artery remodeling, elevated right ventricular
      pressures, increased vascular constriction, and inflammation, is largely due to
      congenital mutations at the BMPR2 site. Both clinical and laboratory studies have
      confirmed the correlation between dysfunction at the BMPR2 genetic site and PAH.
      However, additional basic science and clinical studies suggest a dose-response
      relationship between BMP signaling and the evolution of PAH. RESULTS: Laboratory
      studies found that pulmonary artery smooth muscle cells (PASMCs) under hypoxic
      conditions proliferated in response to BMP-2 in a dose-dependent fashion. Others
      noted that PASMCs extracted from patients with Primary Pulmonary Hypertension
      (PPH) demonstrated abnormal growth responses to transforming growth factor-beta
      (TGF-beta) in a dose-related manner. CONCLUSIONS: The clinical/basic science
      literature appears to document a dose-dependent relationship between BMP and PAH
      (independent of the congenital lesions). Does this mean patients undergoing
      lumbar fusions with BMP are at risk for PAH?

PMID- 25593781
TI  - Progression of cerebellar chronic encapsulated expanding hematoma during late
      pregnancy after gamma knife radiosurgery for arteriovenous malformation.
AB  - BACKGROUND: The etiology and appropriate management strategy of chronic
      encapsulated expanding hematoma during pregnancy after gamma knife radiosurgery
      for arteriovenous malformation (AVM) remain unclear. CASE DESCRIPTION: A 34-year
      old female developed chronic encapsulated expanding hematoma during late
      pregnancy, after angiographic disappearance of cerebellar AVM following two
      courses of gamma knife radiosurgery. The present case implicates pregnancy as a
      potential promoter of growth and enlargement of chronic encapsulated expanding
      hematoma, which may become life-threatening and require surgical intervention.
      CONCLUSION: Immediate surgical management after delivery may be associated with a
      favorable outcome, so close follow-up management and patient education are very
      important in women planning pregnancy.

PMID- 25593782
TI  - Gamma knife radiosurgery to the trigeminal ganglion for treatment of trigeminal
      neuralgia secondary to vertebrobasilar ectasia.
AB  - BACKGROUND: We report the result obtained using Gamma knife stereotactic
      radiosurgery on the trigeminal ganglion (TG) in a patient with trigeminal
      neuralgia (TN) secondary to vertebrobasilar ectasia (VBE). CASE DESCRIPTION:
      Retrospective review of medical records corresponding to one patient with VBE
      related trigeminal pain treated with radiosurgery. Because of the impossibility
      of visualization of the entry zone or the path of trigeminal nerve through the
      pontine cistern, we proceeded with stereotactic radiosurgery directed to the TG.
      The maximum radiation dose was 86 Gy with a 8-mm and a 4-mm collimator. The
      follow-up period was 24 months. The pain disappeared in 15 days, passing from
      Barrow Neurological Institute (BNI) grade V to BNI grade IIIa in 4 months and
      then to grade I. The patient did not experience noticeable subjective facial
      numbness. CONCLUSIONS: This experience showed that Gamma knife radiosurgery was
      effective in the management of VBE-related trigeminal pain, using the TG as
      radiosurgical target.

PMID- 25593783
TI  - Cavernous sinus lesions biopsy with neuronavigation and tip-cut needle.
AB  - BACKGROUND: Transoval biopsy of cavernous sinus (CS) lesions is the last non
      invasive diagnostic option in those 15% of patients in whom etiology remains
      unclear in spite of extensive neuroradiological imaging, clinical assessment, and
      laboratory evaluation. However, there are no guidelines defining indications and
      the most appropriate technique for this procedure. CASE DESCRIPTION: We present
      four patients in whom we performed X-ray and neuronavigation-assisted transoval
      CS biopsies using tip-cut needles. CONCLUSION: The technique described allows the
      operator to determine the optimal angle for entering the CS, avoiding the
      complications due to distorted anatomy, and facilitating orientation once inside
      the CS. It reduces both radiation exposure as well as general anesthesia
      duration.

PMID- 25593784
TI  - Mulitmodality management of rare solitary fibrous tumor can be associated with
      extended survival.
AB  - BACKGROUND: Little is known on the long-term course of patients treated for
      intracranial solitary fibrous tumors (iSFT). We therefore retrospectively
      reviewed the charts of our patients who underwent Gamma Knife radiosurgery (GKRS)
      for iSFT at Klinik Im Park in Zurich and who were treated by one of the authors.
      Between 1994 and 2009, two patients underwent GKRS for iSFT at Klinik Im Park.
      CASE DESCRIPTION: One patient underwent altogether five radiosurgical treatments
      and two craniotomies for iSFT and its local recurrences. The other patient
      underwent two craniotomies and one radiosurgical treatment for iSFT. Both
      patients maintained a Karnofsky performance score 100 during follow-up and both
      were long-term survivors with a follow-up of 9 and 17 years, respectively.
      CONCLUSION: A close follow-up of patients with iSFT and repeat radiosurgery or
      surgery when indicated seems to lead to a favorable long-term outcome.

PMID- 25593785
TI  - Feasibility and Acceptability of an Internet-Based, African Dance-Modified Yoga
      Program for African-American Women with or at Risk for Metabolic Syndrome.
AB  - African-American (AA) women are the segment of the population that experiences
      the highest mortality from metabolic syndrome (MetS). Yoga decreases risk of
      MetS, yet there have been no yoga studies of AA women with or at risk for MetS.
      The purpose of this 4-week study was to test the feasibility and acceptability of
      a culturally tailored, Internet-based intervention, yogic dance (YD), using
      digital videos in a sample of AA women (ages 35-64) at risk for or with MetS. The
      investigators examined the rates of accrual, attrition, and reasons for
      attrition; the feasibility of using the Internet to deliver the intervention; the
      acceptability of the intervention as structured; and any other benefits and/or
      limitations of YD. The study used a single-group, mixed-methods design
      underpinned by social constructivist theory and Pender's Health Promotion Model.
      Twenty-four women provided consent to enroll in the study. After completing in
      person semi-structured interviews and Internet-based measures, including the
      Physical Activity Readiness Questionnaire, and the modified International
      Physical Activity Questionnaire, consented participants engaged in 4-weeks of the
      yogic dance intervention via daily video-based instructions located on the study
      Web site. After the intervention, four women participated in focus groups to
      voice their perceptions of barriers to and benefits from YD and the acceptability
      of using the YD intervention. The investigators analyzed focus group data using
      content/thematic analysis and validated themes with baseline semi-structured
      interviews. The majority of the women (79%) found YD acceptable. Themes that
      emerged from the descriptive data include: (1) Culture is an important aspect of
      yogic dance; and (2) Increased social support would enhance yogic dance
      participation. The integrated results from this feasibility study will inform
      research exploring the complex correlates that influence health behaviors in AA
      women.

PMID- 25593786
TI  - Aortic Atherosclerosis in Systemic Lupus Erythematosus.
AB  - Aortic atherosclerosis (AoA) defined as intima-media thickening or plaques and
      aortic stiffness (AoS) also considered an atherosclerotic process and defined as
      decreased vessel distensibility (higher pulse pressure to achieve similar degree
      of vessel distension) are common in patients with SLE. Immune-mediated
      inflammation, thrombogenesis, traditional atherogenic factors, and therapy
      related metabolic abnormalities are the main pathogenic factors of AoA and AoS.
      Pathology of AoA and AoS suggests an initial subclinical endothelialitis or
      vasculitis, which is exacerbated by thrombogenesis and atherogenic factors and
      ultimately resulting in AoA and AoS. Computed tomography (CT) for detection of
      arterial wall calcifications and arterial tonometry for detection of increased
      arterial pulse wave velocity are the most common diagnostic methods for detecting
      AoA and AoS, respectively. MRI may become a more applicable and accurate
      technique than CT. Although transesophageal echocardiography accurately detects
      earlier and advanced stages of AoA and AoS, it is semi-invasive and cannot be
      used as a screening method. Although imaging techniques demonstrate highly
      variable prevalence rates, on average about one third of adult SLE patients may
      have AoA or AoS. Age at SLE diagnosis; SLE duration; activity and damage;
      corticosteroid therapy; metabolic syndrome; chronic kidney disease; and mitral
      annular calcification are common independent predictors of AoA and AoS. Also, AoA
      and AoS are highly associated with carotid and coronary atherosclerosis. Earlier
      stages of AoA and AoS are usually subclinical. However, earlier stages of disease
      may be causally related or contribute to peripheral or cerebral embolism, pre
      hypertension and hypertension, and increased left ventricular afterload resulting
      in left ventricular hypertrophy and diastolic dysfunction. Later stages of
      disease predisposes to visceral ischemia, aortic aneurysms and aortic dissection.
      Even earlier stages of AoA and AoS have been associated with increased
      cardiovascular and cerebrovascular morbidity and mortality of SLE patients.
      Aggressive non-steroidal immunosuppressive therapy and non-pharmacologic and
      pharmacologic interventions for control of atherogenic risk factors may prevent
      the development or progression of AoA and AoS and may decrease cardiovascular and
      cerebrovascular morbidity and mortality in SLE.

PMID- 25593787
TI  - Acute and chronic hypoxia: implications for cerebral function and exercise
      tolerance.
AB  - PURPOSE: To outline how hypoxia profoundly affects neuronal functionality and
      thus compromise exercise-performance. METHODS: Investigations using
      electroencephalography (EEG) and transcranial magnetic stimulation (TMS)
      detecting neuronal changes at rest and those studying fatiguing effects on whole
      body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated.
      RESULTS: At rest during very early hypoxia (<1-h), slowing of cerebral neuronal
      activity is evident despite no change in corticospinal excitability. As time in
      hypoxia progresses (3-h), increased corticospinal excitability becomes evident;
      however, changes in neuronal activity are unknown. Prolonged exposure (3-5 d)
      causes a respiratory alkalosis which modulates Na+ channels, potentially
      explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates
      the development of peripheral-fatigue; as the severity of hypoxia increases,
      mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the
      predominant factor. The greatest central-fatigue in AH occurs when SaO2 is <=75%,
      a level that coincides with increasing impairments in neuronal activity. CH does
      not improve the level of peripheral-fatigue observed in AH; however, it
      attenuates the development of central-fatigue paralleling increases in cerebral
      O2 availability and corticospinal excitability. CONCLUSIONS: The attenuated
      development of central-fatigue in CH might explain, the improvements in locomotor
      exercise-performance commonly observed after acclimatisation to high altitude.

PMID- 25593789
TI  - Social Support and Smoking during Pregnancy.
AB  - BACKGROUND: Smoking during pregnancy and a lack of social support have been
      identified as independent risk factors for poor birth outcomes. However, the
      influence of social support on smoking during pregnancy remains under
      investigated. This study examined the association between domains of social
      support and smoking during pregnancy. METHODS: Pregnant women during their first
      trimester, attending three inner-city clinics were surveyed using self
      administered questionnaires (N=227). Social support was measured using the
      Interpersonal Support Evaluation List (ISEL). Three domains of social support
      (tangible, appraisal, and belonging) were examined. Multiple logistic regressions
      were conducted; Odds Ratios (OR) and 95% confidence intervals were calculated.
      RESULTS: Per unit increase in the total composite social support scale, there was
      a 6% increased odds of smoking during pregnancy. There was a statistically
      significant interaction between race and social support. While the tangible
      support (OR=1.15; 95% CI: 1.03, 1.27) and appraisal (OR=1.17; 95% CI: 1.05, 1.31)
      domains were significantly associated with smoking among African American women,
      only the belonging support domain was significantly associated with smoking
      during pregnancy among Caucasian women (OR=1.20; 95% CI: 1.02, 1.40).
      CONCLUSIONS: This study provided evidence that racial differences may exist in
      the way social support influences smoking during pregnancy. Future studies are
      needed to understand these racial differences and assist in the design of
      interventions. Considering the importance of social support, strategies for
      smoking cessation intervention should consider racial difference.

PMID- 25593790
TI  - Cognitive Bias Modification for Interpretation in Major Depression: Effects on
      Memory and Stress Reactivity.
AB  - Interpreting ambiguous stimuli in a negative manner is a core bias associated
      with depression. Investigators have used cognitive bias modification for
      interpretation (CBM-I) to demonstrate that it is possible to experimentally
      induce and modify these biases. This study extends previous research by examining
      whether CBM-I affects not only interpretation, but also memory and physiological
      stress response in individuals diagnosed with Major Depressive Disorder (MDD). We
      found that CBM-I was effective in inducing an interpretive bias. Participants
      also exhibited memory biases that corresponded to their training condition and
      demonstrated differential physiological responding in a stress task. These
      results suggest that interpretation biases in depression can be modified, and
      that this training can lead to corresponding changes in memory and to decreases
      in stress reactivity. Findings from this study highlight the importance of
      examining the relations among different cognitive biases in MDD and the
      possibility of modifying cognitive biases.

PMID- 25593788
TI  - The Agrobacterium Ti Plasmids.
AB  - Agrobacterium tumefaciens is a plant pathogen with the capacity to deliver a
      segment of oncogenic DNA carried on a large plasmid called the tumor-inducing or
      Ti plasmid to susceptible plant cells. A. tumefaciens belongs to the class
      Alphaproteobacteria, whose members include other plant pathogens (Agrobacterium
      rhizogenes), plant and insect symbionts (Rhizobium spp. and Wolbachia spp.,
      respectively), human pathogens (Brucella spp., Bartonella spp., Rickettsia spp.),
      and nonpathogens (Caulobacter crescentus, Rhodobacter sphaeroides). Many species
      of Alphaproteobacteria carry large plasmids ranging in size from ~100 kb to
      nearly 2 Mb. These large replicons typically code for functions essential for
      cell physiology, pathogenesis, or symbiosis. Most of these elements rely on a
      conserved gene cassette termed repABC for replication and partitioning, and
      maintenance at only one or a few copies per cell. The subject of this review is
      the ~200-kb Ti plasmids carried by infectious strains of A. tumefaciens. We will
      summarize the features of this plasmid as a representative of the repABC family
      of megaplasmids. We will also describe novel features of this plasmid that enable
      A. tumefaciens cells to incite tumor formation in plants, sense and respond to an
      array of plant host and bacterial signal molecules, and maintain and disseminate
      the plasmid among populations of agrobacteria. At the end of this review, we will
      describe how this natural genetic engineer has been adapted to spawn an entire
      industry of plant biotechnology and review its potential for use in future
      therapeutic applications of plant and nonplant species.

PMID- 25593791
TI  - Insight on automated lesion delineation methods for PET data.
AB  - BACKGROUND: Defining tumour volume for treatment response and radiotherapy
      planning is challenging and prone to inter- and intra-observer variability.
      Various automated tumour delineation methods have been proposed in the
      literature, each having abilities and limitations. Therefore, there is a need to
      provide clinicians with practical information on delineation method selection.
      METHODS: Six different automated positron emission tomography (PET) delineation
      methods were evaluated and compared using National Electrical Manufacturer
      Association image quality (NEMA IQ) phantom data and three in-house synthetic
      phantoms with clinically relevant lesion shapes including spheres with necrotic
      core and irregular shapes. The impact of different contrast ratios, emission
      counts, realisations and reconstruction algorithms on delineation performance was
      also studied using similarity index (SI) and percentage volume error (%VE) as
      performance measures. RESULTS: With the NEMA IQ phantom, contrast thresholding
      (CT) performed best on average for all sphere sizes and parameter settings (SI =
      0.83; %VE = 5.65% +/- 24.34%). Adaptive thresholding at 40% (AT40) was the next
      best method and required no prior parameter tuning (SI = 0.78; %VE = 23.22% +/-
      70.83%). When using SUV harmonisation filtering prior to delineation (EQ.PET),
      AT40 remains the best method without prior parameter tuning (SI = 0.81; %VE =
      11.39% +/- 85.28%). For necrotic core spheres and irregular shapes of the
      synthetic phantoms, CT remained the best performing method (SI = 0.83; %VE =
      26.31% +/- 38.26% and SI = 0.62; %VE = 24.52% +/- 46.89%, respectively). The
      second best method was fuzzy locally adaptive Bayesian (FLAB) (SI = 0.83; %VE =
      29.51% +/- 81.79%) for necrotic core sphere and AT40 (SI = 0.58; %VE = 25.11% +/-
      32.41%) for irregular shapes. When using EQ.PET prior to delineation, AT40 was
      the best performing method without prior parameter tuning for both necrotic core
      (SI = 0.83; %VE = 27.98% +/- 59.58%) and complex shapes phantoms (SI = 0.61; %VE
      = 14.83% +/- 49.39%). CONCLUSIONS: CT and AT40/AT50 are recommended for all
      lesion sizes and contrasts. Overall, considering background uptake information
      improves PET delineation accuracy. Applying EQ.PET prior to delineation improves
      accuracy and reduces coefficient of variation (CV) across different
      reconstructions and acquisitions.

PMID- 25593792
TI  - Long-term therapeutic efficacy of allogenic bone marrow transplantation in a
      patient with mucopolysaccharidosis IVA.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It
      is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase.
      Deficiency of this enzyme leads to accumulation of the specific
      glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation
      has a direct impact on cartilage and bone development, resulting in systemic
      skeletal dysplasia. There is no curative therapy for this skeletal dysplasia.
      This report describes long-term therapeutic efficacy in a 15-year-old boy with a
      severe form of MPS IVA who received successful allogeneic bone marrow
      transplantation (BMT) from his HLA-identical carrier sister. The level of the
      GALNS enzyme in the recipient's lymphocytes reached almost half of normal level
      within two years after BMT. For the successive 9+ years post-BMT, GALNS activity
      in his lymphocytes maintained the same level as the donor's, and the level of
      urinary uronic acid was reduced. Lumbar bone mineral density increased around 50%
      one year later post-BMT and was kept consistent. Radiographs showed that the
      figures of trochanter major and minor appeared, while the epiphyseal dysplasia in
      the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital
      capacity increased to around 20% for the first two years and was maintained.
      Activity of daily life (ADL) was improved in work/study efficacy, respiratory
      status, sleep, joint pain, and frequency of infection. In conclusion, the long
      term study of hematopoetic stem cell transplantation has shown clinical
      improvements in respiratory function, radiograph findings, ADL, and biochemical
      findings, suggesting that it is a potential therapeutic option for patients with
      MPS IVA.

PMID- 25593794
TI  - Localized bullous pemphigoid on sites of radiotherapy and lymphedema in the same
      patient.
AB  - Bullous pemphigoid (BP) is a blistering disorder due to autoantibodies to the
      epidermal basement membrane zone. The triggering factor could be localized damage
      to the skin by physical or chemical agents. We report a case of a 68-year-old
      woman with a three year history of oral lesions of BP following radiotherapy for
      carcinoma of the hypopharynx, and a three month history of BP over lymphedematous
      sites on the right hand and right lower limb. Localized BP induced by
      radiotherapy or lymphedema is rare; both factors working simultaneously in the
      same patient is even rarer. 

PMID- 25593793
TI  - Computational models to understand decision making and pattern recognition in the
      insect brain.
AB  - Odor stimuli reaching olfactory systems of mammals and insects are characterized
      by remarkable non-stationary and noisy time series. Their brains have evolved to
      discriminate subtle changes in odor mixtures and find meaningful variations in
      complex spatio-temporal patterns. Insects with small brains can effectively solve
      two computational tasks: identify the presence of an odor type and estimate the
      concentration levels of the odor. Understanding the learning and decision making
      processes in the insect brain can not only help us to uncover general principles
      of information processing in the brain, but it can also provide key insights to
      artificial chemical sensing. Both olfactory learning and memory are dominantly
      organized in the Antennal Lobe (AL) and the Mushroom Bodies (MBs). Current
      computational models yet fail to deliver an integrated picture of the joint
      computational roles of the AL and MBs. This review intends to provide an
      integrative overview of the computational literature analyzed in the context of
      the problem of classification (odor discrimination) and regression (odor
      concentration estimation), particularly identifying key computational ingredients
      necessary to solve pattern recognition.

PMID- 25593795
TI  - Fractional-targeted phototherapy.
AB  - Targeted ultraviolet B phototherapy is used in the treatment for localized
      variants of psoriasis. We present two cases in which we compared the efficacy of
      lite spot and lite brush in the treatment of psoriasis and vitiligo. 

PMID- 25593796
TI  - The co-occurrence of lichen sclerosus et atrophicus and celiac disease.
AB  - A 53-year-old female patient was admitted to our clinic for generalized
      hypo/hyper-pigmented, partially firm and sclerotic plaques with undefined
      borders. As the skin biopsy taken from the lesion was compatible with lichen
      sclerosus et atrophicus (LSA), the patient was treated with ultraviolet A1 (UVA1)
      treatment. Upon follow-up, she developed abdominal pain and diarrhea. Further
      investigation (including endoscopic and laboratory tests) showed signs consistent
      with celiac disease. After 30 sessions of UVA1 treatment, the skin lesions
      partially regressed. We present this case because the co-occurrence of LSA and
      celiac disease is very rare. 

PMID- 25593797
TI  - Angiokeratoma circumscriptum naeviforme with soft tissue hypertrophy and deep
      venous malformation: A variant of Klippel-Trenaunay syndrome?
AB  - Klippel-Trenaunay syndrome (KTS) is a cutaneous capillary malformation on a limb
      in association with soft tissue swelling with or without bony hypertrophy and
      atypical varicosity. The capillary malformation associated with KTS is port wine
      stain. Angiokeratoma circumscriptum naeviforme (ACN) is a congenital variant of
      angiokeratoma commonly present on the lower limb as a hyperkeratotic plaque. ACN
      is rarely associated with KTS. We report a case of ACN with soft tissue
      hypertrophy and deep venous malformation (possibly a variant of Klippel
      Trenaunay) in a 4-year-old male child. 

PMID- 25593798
TI  - Caffeine as a cause of urticaria-angioedema.
AB  - We report the case of a young woman presenting with recurrent urticaria. The
      episodes occurred both in and out of the workplace. On three occasions it
      presented as urticaria-angioedema, requiring emergency care on one occassion. A
      thorough clinical history along with serological and allergological tests allowed
      a diagnosis of caffeine-induced urticaria-angioedema. We advised the patient to
      follow a caffeine-free diet and to avoid all caffeine or methylxanthine
      containing drugs. After two years of caffeine abstinence, she had not experienced
      any further episodes of urticaria-angioedema. Only a few cases of caffeine
      induced urticaria and/or anaphylaxis have been reported till date, with varying
      outcomes in allergologic investigations. Moreover, several cases are probably
      undiagnosed or misdiagnosed as idiopathic urticaria or as occupational allergy.
      We speculate that hypersensitivity to caffeine rather than autoimmine reaction
      may be the probable cause of urticaria. Caffeine should considered as a potential
      urticaria-inducing agent and should be included in the allergological test
      series. 

PMID- 25593799
TI  - Generalized benign acanthosis nigricans in an infant.
AB  - The generalized form of acanthosis nigricans, especially in infants, is extremely
      rare. Herein we report a 1-year-old female child who developed generalized
      acanthosis nigricans without any evidence of internal malignancy or endocrine
      disorder. This case is being reported for its rarity. 

PMID- 25593800
TI  - Vesiculobullous viral exanthem due to chikungunya in an infant.

PMID- 25593801
TI  - Imatinib causing drug rash with eosinophilia and systemic symptoms: A rare
      cutaneous reaction.

PMID- 25593802
TI  - Post-kala-Azar dermal leishmaniasis: A diagnostic dilemma in a nonendemic area.

PMID- 25593803
TI  - Strawberry-shaped lesion on the chest: cutaneous rhinosporidiosis.
AB  - Rhinosporidiosis is a chronic granulomatous condition caused by the pathogen
      Rhinosporidium seeberi which frequently involves the nasopharynx and occasionally
      affects the skin. The disease has been reported from across the globe but the
      highest incidence has been from south India and Sri Lanka. This disease is
      commonly seen in adult men and the possible mode of transmission to humans is
      thought to be by direct contact with spores through dust, infected clothing,
      fingers, and swimming in stagnant water. The classical presentation is mucosal
      and here we present a case which presented as a growth on the chest wall. And we
      stress the need to keep a high index of suspicion in such cases in endemic areas.

PMID- 25593804
TI  - Favre-Racouchot syndrome.

PMID- 25593805
TI  - Classic porokeratosis of Mibelli.

PMID- 25593806
TI  - Trichostasis spinulosa: An overlooked entity.

PMID- 25593807
TI  - Podagra.

PMID- 25593809
TI  - Herpes iris of Bateman.

PMID- 25593808
TI  - Linear verrucous hemangioma.

PMID- 25593810
TI  - Acral acanthosis nigricans (acral acanthotic anomaly).

PMID- 25593811
TI  - Infantile perianal (perineal) pyramidal protrusion.

PMID- 25593812
TI  - Nerve conduction studies in early tuberculoid leprosy.
AB  - CONTEXT: Hansen's disease is a chronic illness; besides involving skin and
      peripheral nerves, it affects multiple organs. Nerve involvement is always
      present in leprosy, and it may be present much before the patient manifests
      clinically. AIMS: To assess nerve conduction parameters in thickened and
      contralateral non-thickened nerves in early tuberculoid leprosy. MATERIALS AND
      METHODS: Fifty new untreated male patients with tuberculoid and borderline
      tuberculoid leprosy in the age group of 15-50 years with thickened peripheral
      nerves on one side were included in the study. Nerve conduction studies
      consisting of sensory and motor velocity (NCV), distal latencies, and amplitude
      were carried out on thickened ulnar, common peroneal, and posterior tibial nerves
      and contralateral normal nerves. STATISTICAL ANALYSIS USED: Mean values along
      with coefficient of variation were obtained for various parameters. These were
      compared with normal values of the control population. P value was used to verify
      statistical significance. RESULTS: Nerve conduction parameters were deranged in
      most of the thickened nerves. Sensory parameters were affected early in the
      disease process. CONCLUSION: Additional parameters are required to assess nerve
      damage in early cases, where it is more in slow conducting fibers (average
      velocity fibers). Change in conduction velocity may not be marked; this calls for
      the measurement of fast fibers separately because potentials recorded are mainly
      from myelinated fibers.

PMID- 25593814
TI  - Autologous serum skin test as an indicator of chronic autoimmune urticaria in a
      tertiary care hospital in South India.
AB  - BACKGROUND: Autologous serum skin test (ASST) is a simple in-vivo clinical test
      for the detection of basophil histamine releasing activity and to diagnose
      chronic autoimmune urticaria (CAU) among chronic spontaneous urticaria (CSU)
      patients. Diagnosing these patients is also important as they may need high doses
      of antihistamines and systemic corticosteroids during acute exacerbations. AIMS
      AND OBJECTIVES: The aim of this study is to study the prevalence of CAU among
      cases of CSU by using ASST. MATERIALS AND METHODS: This was a cross-sectional
      study done among 48 patients presenting with CSU. Detailed history, physical
      examination and routine investigations were recorded for all patients. ASST was
      done on all the 48 patients. RESULTS: Of the 48 patients included in the study,
      20 patients (41.6%) were ASST positive, while the remaining 28 (58%) were ASST
      negative. The median duration of disease in both ASST positive and negative
      patients was 1 year. ASST positivity was higher (66.6%) among patients with a
      history of round shaped weals, though not statistically significant. ASST
      positivity was seen in 5 (71.4%) out of seven patients with systemic involvement,
      which was again not statistically significant. CONCLUSION: Our study did not show
      any significant difference between patients with and without antibodies regarding
      mean age and sex distribution, clinical morphology of individual weals, duration,
      severity, systemic symptoms, angioedema, atopy, and association with other
      autoimmune conditions.

PMID- 25593813
TI  - Cutaneous adverse drug reactions in Indian population: A systematic review.
AB  - BACKGROUND: Epidemiological data is limited for cutaneous adverse drug reactions
      (CADRs) in India. Most of the Indian studies have small sample size and are of
      limited duration. AIMS: The aim of this study is to analyze CADRs with reference
      to the causative drugs and their clinical characteristics in Indian population.
      MATERIALS AND METHODS: As per selection criteria, electronic databases were
      searched for publications describing CADRs from January-1995 to April-2013 by two
      independent investigators. Data of the causative drugs and clinical
      characteristics were extracted and summarized by absolute numbers, percentages,
      ranges, and means as presented by the authors. The subgroup analysis of causative
      drugs was performed for causality assessment, severe or nonsevere reactions and
      occurrence of common CADRs. Studies showing "definite" and "probable" categories
      of causality analysis were labeled as "definite and probable causality (DPC)
      studies". The other included studies were labeled as "non-DPC studies". RESULTS:
      Of 8337 retrieved references, 18 prospective studies were selected for analysis.
      The pooled incidence was 9.22/1000 total among outpatient and inpatient cases.
      Commonly observed reactions were maculopapular rash (32.39%), fixed drug
      eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic
      epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were
      antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%)
      and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%),
      beta-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is
      observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin
      and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than
      other drugs. Antimicrobials were the main causative drugs for maculopapular rash,
      FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs,
      SJS/TEN, and exfoliative dermatitis were 1.71%, 16.39%, and 3.57%, respectively.
      "Definitely preventable", "probably preventable" and "not preventable" categories
      CADRs were 15.64%, 63.14%, and 34.64%, respectively. CONCLUSION: Antimicrobials,
      NSAIDs and antiepileptic are common causative agents of CADRs in India.
      Antiepileptic agents show high rates of severe cutaneous reactions.

PMID- 25593815
TI  - Response to oral acitretin in lichen amyloidosis.
AB  - We report the therapeutically challenging case of a patient with severe and
      extensive lichen amyloidosis (LA) who responded to oral acitretin and topical
      corticosteroids. Colloid milia and terra firma-forme dermatoses were noted post
      healing of the lesions of LA. There has been no recurrence of lesions post 8
      months of follow-up. We recommend that acitretin should be used more often in
      severe and recalcitrant cases of LA. 

PMID- 25593816
TI  - Lipoid proteinosis (Urbach-Wiethe disease) in two siblings.
AB  - Lipoid proteinosis is a very rare autosomal recessive disorder characterized by
      deposition of hyaline material in the skin and the upper aerodigestive tract.
      Hoarseness of voice occurs very early in life and airway obstruction may occur.
      Characteristic skin lesions include multiple brown atrophic scars over face and
      distal extremities, beaded papules over the margins of the eyelids and verrucous
      nodules over the friction bearing areas (elbows, knees). The overall prognosis is
      good. There is no definitive treatment. 

PMID- 25593817
TI  - Childhood lichen planus pemphigoides triggered by chickenpox.
AB  - Lichen planus pemphigoides (LPP) is a rare autoimmune bullous disorder that is
      rarer in children characterized by bullae on lichen planus like papules and the
      normal looking skin. Clinical, histopathological and direct immunoflourescence
      evaluation is important for the diagnosis of this entity. We report a case of LPP
      in a 5-year-old girl child probably triggered by an episode of preceding
      varicella. Diagnosis was confirmed by histopathology and immunofluorescence
      examination. Histological findings were typical of lichen planus from the biopsy
      taken from a violaceous to erythematous papule and characteristic of bullous
      pemphigoid in the biopsy taken from a bullous lesion with evidence of
      immunoglobulin G and C3 deposition along the basement membrane zone on direct
      immunofluorescence. 

PMID- 25593818
TI  - Postpartum screening after gestational diabetes mellitus: Aiming for universal
      coverage.

PMID- 25593819
TI  - Endemic or epidemic? Measuring the endemicity index of diabetes.

PMID- 25593820
TI  - Adrenal imaging (Part 1): Imaging techniques and primary cortical lesions.
AB  - Adrenal glands can be affected by a variety of lesions. Adrenal lesions can
      either be primary, of adrenal origin, or secondary to other pathologies. Primary
      adrenal lesions can further be either of cortical or medullary origin.
      Functioning adrenal lesions can also give clues to the histologic diagnosis and
      direct workup. Over the years, various imaging techniques have been developed
      that have increased diagnostic accuracy and helped in better characterization of
      adrenal lesions non-invasively. In the first part of the two part series, we
      review adrenal imaging techniques and adrenal cortical tumors such as adenomas,
      adrenocortical tumors, adrenal hyperplasia and oncocytomas. 

PMID- 25593821
TI  - Adrenal imaging (Part 2): Medullary and secondary adrenal lesions.
AB  - Adrenal malignancies can be either primary adrenal tumors or secondary
      metastases, with metastases representing the most common malignant adrenal
      lesion. While imaging cannot always clearly differentiate between various adrenal
      malignancies, presence of certain imaging features, in conjunction with
      appropriate clinical background and hormonal profile, can suggest the appropriate
      diagnosis. The second part of the article on adrenal imaging describes adrenal
      medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal
      incidentalomas and provides an algorithmic approach to adrenal lesions based on
      current imaging recommendations. 

PMID- 25593822
TI  - Thyroid disorders and polycystic ovary syndrome: An emerging relationship.
AB  - As the prevalence of these endocrine dysfunctions increases, the association of
      polycystic ovary syndrome (PCOS) and autoimmune thyroid disease is increasingly
      being recognised. While the causality of this association is still uncertain, the
      two conditions share a bidirectional relationship. The exact nature of this link
      has not been elucidated yet. Both syndromes share certain common characteristics,
      risk factors, and pathophysiological abnormalities. Simultaneously, certain
      etiopathogenetic factors that operate to create these dysfunctions are
      dissimilar. Polycystic appearing ovaries are a clinical feature of
      hypothyroidism, though hypothyroidism should be excluded before diagnosing PCOS.
      Adiposity, increased insulin resistance, high leptin, evidence of deranged
      autoimmunity, all of which are present in both disease states, seem to play a
      complex role in connecting these two disorders. This brief communication explores
      the nature of the relationship between PCOS and hypothyroidism. It reviews
      current data and analyses them to present a unified pathophysiological basis,
      incorporating these complex relationships, for the same. 

PMID- 25593823
TI  - Incretin response in Asian type 2 diabetes: Are Indians different?
AB  - Incretin-based therapy has clearly emerged as one of the most sought out strategy
      in managing type 2 diabetes, primarily because they generally do not causes
      hypoglycemia and possess weight-neutral or weight losing properties. Efficacy
      wise too, these agents, are more or less similar to commonly used drugs metformin
      and sulfonylureas. Interestingly, some studies recently suggested that glycemic
      response to these incretin-based therapies could also differ ethnicity-wise.
      Subsequently, meta-analysis from these studies also suggested that Asians may
      have better response to these incretin-based therapies. This review will be an
      attempt to critically analyze those studies available in literature and to
      address as to why East-Asians and South-Asians may have different incretin
      response compared to non-Asians. 

PMID- 25593824
TI  - Amadori albumin in diabetic nephropathy.
AB  - Nonenzymatic glycation of macromolecules in diabetes mellitus (DM) is accelerated
      due to persistent hyperglycemia. Reducing sugar such as glucose reacts non
      enzymatically with free ?-amino groups of proteins through series of reactions
      forming Schiff bases. These bases are converted into Amadori product and further
      into AGEs. Non enzymatic glycation has the potential to alter the biological,
      structural and functional properties of macromolecules both in vitro and in vivo.
      Studies have suggested that amadori as well as AGEs are involved in the micro
      macro vascular complications in DM, but most studies have focused on the role of
      AGEs in vascular complications of diabetes. Recently putative AGE-induced patho
      physiology has shifted attention from the possible role of amadori-modified
      proteins, the predominant form of the glycated proteins in the development of the
      diabetic complications. Human serum albumin (HSA), the most abundant protein in
      circulation contains 59 lysine and 23 arginine residues that could, in theory be
      involved in glycation. Albumin has dual nature, first as a marker of intermediate
      glycation and second as a causative agent of the damage of tissues. Among the
      blood proteins, hemoglobin and albumin are the most common proteins that are
      glycated. HSA with a shorter half life than RBC, appears to be an alternative
      marker of glycemic control as it can indicate blood glucose status over a short
      period (2-3 weeks) and being unaffected by RBCs life span and variant
      haemoglobin, anemia etc which however, affect HbA1c. On the other hand, Amadori
      albumin may accumulate in the body tissues of the diabetic patients and
      participate in secondary complications. Amadori-albumin has potential role in
      diabetic glomerulosclerosis due to long term hyperglycaemia and plays an
      important role in the pathogenesis of diabetic nephropathy. This review is an
      approach to compile both the nature of glycated albumin as a damaging agent of
      tissues and as an intermediate diagnostic marker and its potential role in
      diabetic nephropathy. 

PMID- 25593825
TI  - Feasibility, efficacy, and safety of a simple insulin infusion protocol in a
      large volume cardiac surgery unit in India.
AB  - AIM: Inpatient hyperglycemia management is essential, but difficult to achieve
      especially in a large volume cardiac surgery setup, thus necessitating use of
      nurse-led insulin protocols. A rapid flux of nurses dealing with a huge workload
      has been a cause for traditionally not using nurse-led protocols in most Indian
      institutes. The challenges we faced were to have a simple protocol for the nurses
      to accept it without compromising on glycemic control. Therefore, this
      observational study was planned to measure the efficacy and safety of the insulin
      infusion protocol in cardiac surgery patients. MATERIALS AND METHODS: Insulin
      protocol was implemented, using seven fixed columns of infusion with the nurse
      making decisions to initiate and titrate doses based on simple rules. Blood
      glucose (BG) data captured from blood gas analyzers (glucometrics) in the
      intervention group (i.e., after protocol implementation) were compared to control
      group (i.e., before the protocol implementation). RESULTS: The mean BG for the
      first 48 h was lower in the intervention group as compared to control group,
      without an increase in the episodes of hypoglycemia. The nurses found the
      protocol easy to understand, less time-consuming and there was no protocol
      deviation over 8 months after implementation. CONCLUSION: A small change in the
      process, allowing nurses to titrate insulin doses based on some rules and having
      seven fixed columns of insulin infusion rates, improved glycemic control and
      efficiency.

PMID- 25593826
TI  - Association between serum albumin and glycated hemoglobin in Asian Indian
      subjects.
AB  - BACKGROUND: Protein glycation plays a significant role in diabetic complications.
      Glycated hemoglobin (HbA1c) is a known predictor of diabetes and its
      complications. Albumin, found to be profoundly glycated in diabetes, and its
      level could regulate plasma protein as well as hemoglobin glycation. AIM: We
      aimed to evaluate the association between variations in albumin level with HbA1c
      in the Asian Indian population. MATERIALS AND METHODS: We screened data of 929
      subjects who have had a simultaneous measurement of fasting plasma glucose (FPG),
      HbA1c and albumin levels via the same blood collection. Data were analyzed by
      SPSS for 610 subjects who met the study criteria. RESULTS: There was a
      significant negative correlation between HbA1c and albumin concentration (r = 
      0.284; P < 0.001). Univariate analysis showed the statistically significant
      decrease of average HbA1c but not for fasting plasma glucose (FPG) across
      increasing tertiles of albumin. Stepwise multiple regression model showed a
      significant correlation between HbA1c and serum albumin (P < 0.05), FPG (P <
      0.001), hemoglobin (Hb) (P < 0.001) and serum globulin (P < 0.05). FPG was the
      strongest predictor (63.4%) of variation of HbA1c. The albumin concentration (r =
      -0.114) accounted for 0.3% (P < 0.05) of the total variance in HbA1c independent
      of age, body mass index, FPG, Hb, creatinine, total protein and globulin. It was
      also observed that HbA1c decreases with increasing albumin concentration in those
      having FPG between 100 to <126 mg/dl. CONCLUSION: Serum albumin negatively
      correlates with HbA1c in Asian Indians independent of other variables. This study
      suggests that predicting diabetes and its complication based on the HbA1c needs
      to be further investigated in Indian subjects.

PMID- 25593827
TI  - Relationship of salivary cortisol and anxiety in recurrent aphthous stomatitis.
AB  - BACKGROUND AND OBJECTIVES: Recurrent aphthous stomatitis (RAS) is one of the most
      frequently encountered oral mucosal disorders. Despite extensive amount of
      research, the etiology of RAS remains unclear. Psychological-emotional factors
      were considered as one of the major predisposing factors. The aim of the study
      was to assess the levels of anxiety and salivary cortisol levels in patients with
      RAS and also to determine the association and relationship of salivary cortisol
      levels to variations of stress. MATERIALS AND METHODS: A total of 30 patients
      suffering with RAS, along with the same number of age and sex matched healthy
      controls were included in the study. Saliva was collected from all the subjects
      at 9.00 am to avoid diurnal variations of cortisol levels. Salivary cortisol
      levels were measured by competitive enzyme linked immunosorbent assay. Anxiety
      levels of both groups were measured by using Hamilton's anxiety scale. Student's
      t-test was used to compare the anxiety and salivary cortisol levels between both
      groups. RESULTS: The mean salivary cortisol level of the RAS group showed a very
      highly significant difference (P = 0.000) from the controls. The mean anxiety
      scores of the RAS group showed a very highly significant difference (P = 0.000)
      from the controls. The values of Pearson correlation coefficient between anxiety
      and salivary cortisol was 0.980 and one with a P value of 0.000 showing that
      there is a highly positive correlation between anxiety and salivary cortisol.
      CONCLUSION: Results suggest that anxiety may be involved in the pathogenesis of
      RAS. Thus besides traditional treatment of RAS patients, our findings suggest
      that psychological support is also needed.

PMID- 25593828
TI  - No impact of dietary iodine restriction in short term development of
      hypothyroidism following fixed dose radioactive iodine therapy for Graves'
      disease.
AB  - BACKGROUND: The increased incidence of autoimmune thyroid disease with increasing
      dietary iodine intake has been demonstrated both epidemiologically and
      experimentally. The hypothyroidism that occurs in the first year following
      radioactive iodine therapy is probably related to the destructive effects of the
      radiation and underlying ongoing autoimmunity. OBJECTIVE: To study the outcomes
      at the end of six months after fixed dose I, (131)therapy for Graves' disease
      followed by an iodine restricted diet for a period of six months. MATERIALS AND
      METHODS: Consecutive adult patients with Graves' disease planned for I(131)
      therapy were randomized either to receive instructions regarding dietary iodine
      restriction or no advice prior to fixed dose (5mCi) I(131) administration.
      Thyroid functions and urinary iodine indices were evaluated at 3(rd) and 6(th)
      month subsequently. RESULTS: Forty seven patients (13M and 34F) were assessed, 2
      were excluded, 45 were randomized (Cases 24 and Controls 21) and 39 patients
      completed the study. Baseline data was comparable. Median urinary iodine
      concentration was 115 and 273 MUg/gm creat (p = 0.00) among cases and controls
      respectively. Outcomes at the 3(rd) month were as follows (cases and controls);
      Euthyroid (10 and 6: P = 0.24), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid
      (7 and 8: P = 0.64). Outcomes at the end of six months were as follows (cases and
      controls); Euthyroid (10 and 5: P = 0.12), Hypothyroid (3 and 5: P = 0.38) and
      Hyperthyroid (7 and 9: P = 0.43). Of the hypothyroid patients 5 (cases 1 and
      controls 4: P = 0.13) required thyroxine replacement. CONCLUSIONS: There was no
      statistical significant difference in the outcome of patients with dietary iodine
      restriction following I(131) therapy for Graves' disease.

PMID- 25593829
TI  - Correlations among obesity-associated gene polymorphisms, body composition, and
      physical activity in patients with type 2 diabetes mellitus.
AB  - CONTEXT: Various studies have focused on the correlation between beta2-adrenergic
      receptor (beta2AR), the beta3-adrenergic receptor (beta3AR), and the uncoupling
      protein 1 (UCP1) polymorphisms and obesity in patients with type 2 diabetes
      mellitus (T2DM). AIMS: We examined the correlation between these polymorphisms
      and body composition variables and between body composition and lifestyle
      variables in Japanese T2DM patients. MATERIALS AND METHODS: Of the 48, T2DM
      outpatients in Kanagawa prefecture recruited for participation, 32 (6 men and 26
      women) met the study criteria and were enrolled. Obesity-related gene
      polymorphisms were identified in 3 genes beta3AR, UCP1, and beta2AR using the
      SMart amplification process. Body composition variables were measured using a
      body composition analyzer. Data regarding food and nutrient consumption, family
      history, and lifestyle factors were collected via administration of
      questionnaires. RESULTS: Because significant differences in body composition
      variables were found between men and women, statistical analysis was performed
      with data from the 25 female subjects only. On the basis of results of genetic
      testing, the subjects were divided into genotype groups for two-group and three
      group comparison. The beta3AR, UCP1, and beta2AR polymorphisms and body
      composition significantly correlated with the percentage of subcutaneous fat in
      both arms as compared with the wild type or hetero groups with beta3AR
      polymorphisms. However, physical activity correlated with several body
      composition variables. CONCLUSIONS: These results suggest that obesity in T2DM
      patients is not the result of presence of an obesity-related gene polymorphism
      but rather the absence of daily physical activity.

PMID- 25593830
TI  - Central adiposity is significantly higher in female compared to male in Pakistani
      type 2 diabetes mellitus patients.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) rates are increasing rapidly in South
      Asians. Cardiovascular complications are more frequent and occur earlier in our
      patients than patients in many other ethnic groups. Reasons for this are not
      fully understood. AIMS: The aim of this study is to evaluate the body total and
      central fat percentage in type 2 Diabetes Mellitus patients and to check
      correlation with BMI, waist circumference and metabolic profile. SETTINGS AND
      DESIGN: A cross-sectional study conducted at endocrine clinic, Aga Khan
      University Hospital Karachi, Pakistan, from May to December 2012. MATERIALS AND
      METHODS: Patients of either gender with type 2 diabetes mellitus were randomly
      selected. A separate proforma for each patient was recorded for demographics,
      risk factors, bioelectrical impedance measurement for body fat and
      investigations. STATISTICAL ANALYSIS: Correlation between body fat and other
      covariate were compared by Pearson correlation coefficient test. A P < 0.05 was
      considered significant. SPSS19.0 was used to analyze the data. RESULTS: One
      hundred and seventy five patients (95 male and 80 female) with mean age of 54.1
      +/- 12 years were evaluated. Mean duration of diabetes was 8.1 years, mean HbA1c
      was 8.1% and 53.7% were on oral agents and rest were on insulin with or without
      oral agents. Hypertension was present in 65.7%, 13.7% had known coronary artery
      disease and 2.3% had cerebrovascular disease. Mean BMI in males was 29.1 +/- 4.74
      kg/m(2) and females 31.7 +/- 5.3 kg/m(2). Mean waist circumference in males was
      107.3 +/- 16.6 cm and 103 +/- 12 cm in females. Total body fat percentage (%BF)
      in males was 30.9 +/- 7.1% and females 40 +/- 8.2% with 89% of the total cohort
      having total body fat percentage above the normal, less than 25% central fat
      percentage was 13.3 +/- 5.2% in males and 14.6 +/- 5.5% in females with 79.4% of
      cohort having increased central fat (normal <9%). Total and central body fat
      correlated with BMI (r = 0.68, P < 0.001) and waist circumference (r = 0.66, P <
      0.001) but not with HbA1c, triglyceride level or with fasting or random blood
      glucose levels. Women had significantly higher total body fat percentage compared
      to men (P < 0.001) although central fat percentage was similar in both sexes.
      CONCLUSIONS: High body fat percentage, waist circumference are seen especially in
      woman and central body fat percentage in both sexes among patients with type 2
      diabetes mellitus in Pakistan. Body fat percentage should be measured and
      followed as this may be an important contributing factor to the high
      macrovascular complication rate in this part of world.

PMID- 25593831
TI  - Impact of the Pro12Ala polymorphism of the PPARgamma2 gene on diabetes and
      obesity in a highly consanguineous population.
AB  - BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) are members
      of the nuclear hormone receptor subfamily of transcription factors. It has been
      reported that they play important roles in obesity and the development of type 2
      diabetes mellitus (T2DM). MATERIALS AND METHODS: This case-control study was
      carried out among 764 Qatari patients with diabetes and 764 healthy subjects
      above 20 years of age at Primary Healthcare Clinics (PHCs) from January 2011 to
      December 2012. Face-to-face interviews were based on a questionnaire that
      included variables such as age, sex, sociodemographic status, body mass index
      (BMI) and other clinical parameters. The Pro12Ala in the PPARgamma2 gene was
      detected on the LightCycler using two specific probes. Univariate and
      multivariate statistical analysis were performed. RESULTS: The study revealed
      that in the diabetes group, Pro/(10.2% vs 9.4%; P = 0.606) and Ala/Ala (1.4% vs
      0.9%; P = 0.343) were higher than in controls, whereas Pro/Pro (88.4% vs 89.7%;P
      = 0.413) was lower in diabetes patients, but no significant difference was
      observed among the genotype groups. In obese patients with diabetes, Pro/Pro (89%
      vs 89.9%;P = 0.792) and Pro/Ala (8.9% vs 10.1%;P = 0.671) were lower than in
      obese healthy subjects. No homozygous Ala/Ala was found in obese healthy
      subjects, whereas 6 Ala/Ala homozygotes were in obese diabetes group. But in
      diabetes group, obese patients had higher homozygous of Pro/Pro (89.3% vs 87.8%;P
      = 0.523) and Ala/Ala (1.8% vs 1.2%;P = 0.771) compared to non-obese patients.
      CONCLUSION: The current study did not reveal an association between the Pro12Ala
      polymorphism of the PPAR gamma2 gene and type 2 diabetes (T2D) in Qatari's
      population.

PMID- 25593832
TI  - Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy.
AB  - INTRODUCTION: Data from several studies suggest that pretreatment with
      antithyroid drugs (ATD) before (131)I increases the risk of treatment failure.
      This effect has been demonstrated more consistently with propylthiouracil than
      with carbimazole (CMZ) or methimazole (MMI). Men with Graves' disease (GD) have a
      lower rate of remission with (131)I compared to women and the impact of long-term
      ATD pretreatment on the success of (131)I is unknown. The objective of our study
      was to compare the efficacy of fixed doses of radioiodine between patients with
      and without long-term CMZ pretreatment. MATERIALS AND METHODS: We performed a
      retrospective study on 335 male patients with GD treated with (131)I from 1998 to
      2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients
      received (131)I without pretreatment. We compared the success rate of a single
      dose of (131)I, between patients with and without long-term CMZ pretreatment.
      RESULTS: The success rate of a single dose of (131)I was significantly higher in
      patients without pretreatment than in patients who were pretreated with CMZ
      (91.4% vs. 82.3%, P = 0.01). The rate of hypothyroidism in the first 6 months
      after (131)I therapy was significantly higher in patients without pretreatment
      (55.1% vs. 44.6%, P = 0.05). There was also a trend for higher cumulative rate of
      hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%).
      CONCLUSION: Male patients with Graves' hyperthyroidism pretreated with CMZ have
      lower efficacy with 131I therapy compared to nonpretreated patients. CMZ
      pretreatment given for a prolonged period reduces the efficacy of (131)I therapy.

PMID- 25593833
TI  - Assessment of thyroid and gonadal function in liver diseases.
AB  - INTRODUCTION: Liver is involved with the synthesis of carrier proteins and
      metabolism of various hormones and liver diseases may, therefore, be associated
      with various endocrine disturbances. This study was conducted to assess thyroid
      and gonadal function in subjects with acute hepatitis (AH), chronic liver disease
      (CLD), and those who had undergone liver transplantation (LT). MATERIALS AND
      METHODS: Patients with AH, CLD with Child-Pugh stage A (CLD-1) and Child-Pugh
      stage B or C (CLD-2), and LT seen at our tertiary level hospital were assessed
      clinically, biochemically, and for thyroid and gonadal functions besides 25
      healthy controls. RESULTS: Thyroid dysfunction and hypogonadism were present in
      14 (16%) and 24 (28%) patients with liver diseases respectively. Among thyroid
      dysfunction, the commonest was sick euthyroid syndrome six (7%), followed by
      subclinical hypothyroidism in three patients (3.5%), subclinical hyperthyroidism
      and thyrotoxicosis in two patients each (2.3%) and overt hypothyroidism in one
      patient. Among patients with LT and AH groups, the only abnormality was
      significantly lower total T3 compared with healthy controls. The CLD2 group had
      significantly lower levels of all thyroid hormones compared with controls and
      CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50%) followed
      by LT (3; 33%), CLD-1 (4; 20%), and AH (3; 14%). Hypogonadism was predicted by
      older age, lower levels of serum albumin, total cholesterol, and triglycerides
      and higher levels of plasma glucose, serum bilirubin, aspartate transaminases,
      and international normalized ratio. Gonadal functions showed recovery following
      LT. CONCLUSIONS: Thyroid dysfunction and hypogonadism form an important part of
      the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic
      functions of liver disease predicts presence of hypogonadism.

PMID- 25593834
TI  - Aldose reductase C-106T gene polymorphism in type 2 diabetics with
      microangiopathy in Iranian individuals.
AB  - BACKGROUND: Aldose reductase (AR) is the rate-limiting enzyme in the glucose
      metabolism, which has been implicated in the pathogenesis of diabetic
      microvascular complications (MVCs). Frequent C-106T polymorphism in the promoter
      of the AR gene may change the expression of the gene. AIMS: The aim of the
      following study is to study the association between AR C106T genotypes and
      diabetic MVCs in Iranian population. MATERIALS AND METHODS: We included 206 type
      2 diabetic patients categorized into two groups according to the presence or
      absence of diabetic microangiopathy. The cases of interest were diabetic
      neuropathy, retinopathy and nephropathy identified during clinical and or
      laboratory examination. In addition, 114 age- and sex-matched individuals were
      selected to serve as a control group. AR genotyping was done using an
      amplification gel electrophoresis. RESULTS: The frequency of CC genotype was
      specifically higher in subjects with diabetic retinopathy as compared to those
      without it (53.2% vs. 38.1%, P = 0.030). Patients with diabetic microangiopathy
      in general; however, did not differ significantly between AR genotype groups.
      CONCLUSION: The C-106T polymorphism in the AR gene is likely a risk factor for
      development of only retinal complication of diabetes microvascular in Iranian
      individuals.

PMID- 25593835
TI  - Primary hyperparathyroidism presenting as hypercalcemic crisis: Twenty-year
      experience.
AB  - CONTEXT: To study hyperparathyroid-induced hypercalcemic crisis (HIHC). AIMS: We
      see very advanced cases of primary hyperparathyroidism (PHPT) and therefore, we
      sought to determine the incidence of HIHC in our surgically-treated PHPT
      patients, clinical presentation, and short- and long-term results with the use of
      bisphosphonate therapy and expeditious parathyroidectomy over a 20-year period at
      a single institution. SETTINGS AND DESIGN: Retrospective review of PHPT patients
      at Department of Endocrine Surgery, a tertiary care referral center. MATERIALS
      AND METHODS: Retrospective review of 177 patients of advanced PHPT who underwent
      parathyroidectomy at a single institution from 1989 to 2010. All patients with
      serum calcium >=14 mg/dl (>=3.5 mmol/l) were included in HIHC group. STATISTICAL
      ANALYSIS: Analysis of variance (ANOVA) was used to determine differences between
      groups. Data is expressed as mean +/- standard error of the mean (SEM); P values
      less than 0.05 were considered significant. RESULTS: We observed a higher
      incidence of HIHC (n = 37, 21%) with higher incidence of pancreatitis (n = 5,
      13.5%). Crisis patients had heavier (6,717 mg) glands. Use of bisphosphonate
      therapy in seven crisis patients resulted in quicker lowering of serum calcium
      (mean: 4.5 vs 14.6 days in other crisis patients, P = 0.027) permitting early
      surgery. The incidence of postoperative hypocalcemia was not higher in these
      patients. Although the parathyroid adenoma was common pathology in both the
      groups, the incidence of parathyroid carcinoma was higher in crisis group
      (10.8%). Outcome with regards to postoperative eucalcemia was similar in both
      groups. CONCLUSIONS: Crisis patients are at risk of developing pancreatitis.
      Bisphosphonate therapy has the potential to quickly lower the serum calcium
      permitting early surgery without added risk of postoperative hypocalcemia.
      Successful and sustained eucalcemia with excellent long-term survival is possible
      with use of bisphosphonates and semi-emergent, focused parathyroidectmy.

PMID- 25593836
TI  - Status of iodine nutrition among pregnant mothers in selected districts of
      Uttarakhand, India.
AB  - BACKGROUND: Uttarakhand state is a known endemic area for iodine deficiency.
      OBJECTIVE: The present study was conducted with an objective to assess the iodine
      nutritional status amongst pregnant mothers (PMs) in districts: Pauri (P),
      Nainital (N) and Udham Singh Nagar (USN) of Uttarakhand state. MATERIALS AND
      METHODS: Thirty clusters from each district were selected by utilizing the
      population proportionate to size cluster sampling methodology. A total of 1727
      PMs from P (481), N (614) and USN (632) were included. The clinical examination
      of the thyroid of each PM was conducted. Urine and salt samples were collected
      from a sub samples of PMs enlisted for thyroid clinical examination. RESULTS: The
      total Goiter rate was found to be 24.9 (P), 20.2 (N) and 16.1 (USN)%. The median
      urinary iodine concentration (UIC) levels were found to be 110 MUg/L (P), 117.5
      MUg/L (N) and 124 MUg/L (USN). The percentage of PMs consuming salt with iodine
      content of 15 ppm and more was found to be 57.9 (P), 67.0 (N) and 50.3 (USN).
      CONCLUSION: The findings of the present study revealed that the PMs in all three
      districts had low iodine nutritional status as revealed by UIC levels of less
      than 150 MUg/L.

PMID- 25593837
TI  - Clinical experience of switching from biphasic human insulin to biphasic insulin
      aspart 30 in Indian patients with type 2 diabetes in the A1chieve study.
AB  - AIM: The aim of the following study is to evaluate the safety and effectiveness
      of switching from biphasic human insulin (BHI) to biphasic insulin aspart 30
      (BIAsp 30) in Indian patients with type 2 diabetes as a sub-analysis of the 24
      week, non-interventional A1chieve study. MATERIALS AND METHODS: Indian patients
      switching from BHI to BIAsp 30 based on the physicians' decisions were included.
      The primary outcome was the incidence of serious adverse drug reactions (SADRs),
      including major hypoglycemic events; secondary outcomes included changes in
      hypoglycemia in the 4 weeks preceding baseline and week 24 and changes from
      baseline to week 24 in glycated hemoglobin A1c (HbA1c), fasting plasma glucose
      (FPG), postprandial plasma glucose (PPPG), body weight and quality of life (QoL).
      RESULTS: Overall, 1976 patients (mean +/- standard deviation age, 55.1 +/- 10.6
      years and diabetes duration, 10.1 +/- 5.3 years) on a mean pre-study BHI dose of
      0.44 +/- 0.18 U/kg were included. The mean BIAsp 30 dose was 0.43 +/- 0.17 U/kg
      at baseline and 0.44 +/- 0.17 U/kg at week 24. No SADRs were reported. The
      proportion of patients reporting overall hypoglycemic events reduced
      significantly from baseline to week 24 (15.0% vs. 2.9%, P < 0.0001). The mean
      HbA1c level improved significantly from 9.1 +/- 1.4% at baseline to 7.5 +/- 1.0%
      at week 24, along with improvements in FPG, post-breakfast PPPG and QoL (P <
      0.001). The mean body weight decreased from 69.3 +/- 10.8 kg at baseline to 69.1
      +/- 10.4 kg at week 24 (P = 0.003). CONCLUSION: Switching from BHI to BIAsp 30
      therapy was well-tolerated and was associated with improved glycemic control.

PMID- 25593838
TI  - Effects of acute organophosphate poisoning on pituitary target gland hormones at
      admission, discharge and three months after poisoning: A hospital based pilot
      study.
AB  - BACKGROUND: Organophosphate compound (OPC) poisoning is common in the developing
      countries such as India. The acute and later effects of OPC poisoning on
      pituitary and target gland hormones is largely unknown. MATERIALS AND METHODS:
      This prospective study was conducted at Postgraduate Institute of Medical
      Education and Research between January 2012 and March 2013. Fourteen patients (8
      males, age 18-50 years) with acute OPC poisoning were included in the study based
      on the history and clinical features, documented decreased in plasma
      cholinesterase activity or presence of the OPC in gastric lavage/blood samples.
      The hormonal parameters were done at baseline, at the time of discharge and at
      three months of follow-up. RESULTS: A total of 14 patients out of 46 with the
      mean age of 30.1 +/- 10.3 years were finally eligible for the study. Hormonal
      alterations at admission were similar to sick euhormonal syndrome. Overall 7 of
      them had nine hormonal deficits at three months of follow up, 4 having sub normal
      basal cortisol level and two each had low testosterone and growth hormone and
      only one had thyroxine deficiency. CONCLUSION: Acute organophosphate poisoning
      results in endocrine dysfunction akin to sick euhormonal syndrome. However, in a
      small subset of patients, varying level of hormonal insufficiency may occur
      either at admission or later. These observations need re-validation in a larger
      group of patients with specific OPC.

PMID- 25593839
TI  - Evaluation of glutathione S-transferase T1 deletion polymorphism on type 2
      diabetes mellitus risk in Zoroastrian females in Yazd, Iran.
AB  - BACKGROUND: There has been much interest in the role of free radicals and
      oxidative stress in the pathogenesis of diabetes mellitus (DM). The aim of this
      study was to assess the possible association between genetic polymorphisms of the
      glutathione S-transferase-Theta (GSTT1) and the risk of the development of DM in
      Zoroastrian females in Yazd, Iran. MATERIALS AND METHODS: This was a case-control
      study in which GSTT1 polymorphism was genotyped in 51 randomly selected DM
      patients and 50 randomly selected healthy controls among Zoroastrian females
      whose ages ranged from 40 to 70. RESULTS: The frequencies of GSTT1 null genotype
      and GSTT1 present were 72% and 28%, respectively, in control samples, while in
      patients with type 2 diabetes (T2DM), the frequencies of GSTT1 null genotype and
      GSTT1 present were 27.5% and 72.5%, respectively. There were higher levels of
      triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density
      lipoprotein (LDL), Urea, and high-density lipoprotein (HDL) in cases of GSTT1
      null genotype compared to the GSTT1 present genotype in controls. CONCLUSIONS:
      Our results indicated that healthy subjects had a higher frequency of the GSTT1
      null genotype than patients with T2DM. However, we observed no significant
      association between the GSTT1 null genotype and T2DM in the current study.

PMID- 25593840
TI  - Effectiveness and safety of fixed dose combination of acarbose/metformin in
      Indian Type 2 diabetes patients: Results from observational GLOBE Study.
AB  - Primary objective - evaluate effectiveness and safety of acarbose/metformin fixed
      dose FDC on glycemic control in Indian T2DM patients in real life clinical
      setting. Secondary objective - evaluate safety and satisfaction of treatment.
      MATERIALS AND METHODS: Open-label, prospective, multicentre, single-arm, non
      interventional study. Patients included were aged >=18 years with T2DM on
      Acarbose (25/50 mg) and Metformin (500 mg) FDC. Glycemic parameters were recorded
      during observation. RESULTS: Total 9364 patients were enrolled in the study (mean
      age, 50.7 years and 60.1% were male). Mean (SD) FBG and PPG was significantly
      reduced by 42.4 (32.6) mg/dl (P < 0.0001) and 80.2 (49.7) mg/dl (P < 0.0001)
      respectively at the end of observation. Mean (SD) HbA1c reduced by -1.0% (0.8) to
      7.3% (0.7) at the last follow-up visit (P <0.0001). Majority of patients (97.5%)
      and physicians (98.42%) were satisfied with acarbose/metformin FDC treatment.
      Also, significant reduction in body weight by -1.7 (2.2) kg was observed (P <
      0.0001). Patients with known T2DM and newly diagnosed showed a similar glycemic
      control (P < 0.0001). Drug-related adverse events were reported by only 1.4%
      patients mostly gastrointestinal. CONCLUSIONS: Acarbose/metformin FDC was
      efficacious, safe well accepted in routine clinical practice. It was well
      tolerated without significant risk of hypoglycemia and can be used in early T2DM
      management.

PMID- 25593841
TI  - Association of depression with common carotid artery intima media thickness and
      augmentation index in a large Urban South Indian population- The Chennai Urban
      Rural Epidemiology Study (CURES - 138).
AB  - AIM: The aim of the study was to assess the relationship of depression with
      carotid intima media thickness and augmentation index in Asian Indians. RESEARCH
      DESIGN AND METHODS: For this study, 1505 subjects were randomly selected from a
      population based study conducted in Chennai, South India. Right common carotid
      artery intima medial thickness [IMT] was determined using high-resolution B-mode
      ultrasonography. Augmentation index [AI] was measured using the Sphygmocor
      apparatus. Depressive symptoms were assessed using a previously validated
      instrument, the Patient Health Questionnaire -12 (PHQ -12). RESULTS: Of the 1505
      subjects included in this study, depressive symptoms were present in 16.6% (n =
      250) of the subjects. The mean IMT and AI values among subjects with depression
      were significantly higher than those without depression [0.83 +/- 0.43 mm vs 0.73
      +/- 0.12 mm, P < 0.001] and IMT was higher in females with depression while AI
      was higher in males with depression. However, both IMT and AI were higher among
      those with depression in both genders. In multiple logistic regression model,
      depressive symptoms were associated with IMT even after adjusting for age,
      gender, body mass index, fasting plasma glucose, serum cholesterol and
      hypertension (Odds ratio [OR] =2.17, 95% Confidence intervals [CI]:1.01- 4.63, P
      = 0.047) but in the case of AI, the significance was lost in the adjusted model
      (OR = 1.01, 95% CI: 0.991-1.02, P = 0.445). CONCLUSION: Among Asian Indians,
      presence of depressive symptoms was associated with carotid intima media
      thickness and Augmentation index, even after adjusting for potential confounders.

PMID- 25593842
TI  - Endocrine alterations in HIV-infected patients.
AB  - AIMS AND OBJECTIVES: To study the frequency of thyroid, adrenal and gonadal
      dysfunction in newly diagnosed HIV-infected patients and to correlate them at
      different levels of CD4 cell counts. MATERIALS AND METHODS: Forty-three HIV
      positive cases were included in the study group. Cases were divided into three
      groups on the basis of CD4 cell count. Serum free T3, free T4, TSH, Cortisol,
      FSH, LH, testosterone and estradiol were estimated by the radioimmunoassay
      method. Hormone levels between cases were compared and their correlation with CD4
      count was analyzed. RESULTS: Prevalence of gonadal dysfunction (88.3%) was the
      most common endocrine dysfunction followed by thyroid (60.4%) and adrenal
      dysfunction (27.9%). Secondary hypogonadism (68.4%) was more common than primary
      (31.6%). Low T3 syndrome, that is, isolated low free T3, was the most common
      (25.6%) thyroid dysfunction followed by secondary hypothyroidism (16.2%) and
      subclinical hypothyroidism (11.6%). Adrenal excess (16.3%) was more common than
      adrenal insufficiency (11.6%). The difference in hormonal dysfunction between
      male and female was statistically insignificant (P > 0.05). 27.9% of patients had
      multiple hormone deficiency. There was negligible or no correlation between CD4
      count and serum hormone level. CONCLUSION: In our study, endocrine dysfunction
      was quite common among HIV-infected patients but there was no correlation between
      hormone levels and CD4 count. Endocrine dysfunctions and role of hormone
      replacement therapy in HIV-infected patient needs to be substantiated by large
      longitudinal study, so that it will help to reduce morbidity, improve quality of
      life.

PMID- 25593843
TI  - A randomized placebo-controlled trial of the efficacy of denosumab in Indian
      postmenopausal women with osteoporosis.
AB  - INTRODUCTION: Osteoporosis is a serious condition affecting up to 50% of Indian
      postmenopausal women. Denosumab reduces bone resorption by targeting the receptor
      activator of nuclear factor-kappaB ligand. This study assessed the efficacy and
      safety of denosumab in Indian postmenopausal women with osteoporosis. MATERIALS
      AND METHODS: In this double-blind, multicenter, phase 3 study, 250 Indian
      postmenopausal women aged 55 to 75 years (T-score <-2.5 and >-4.0 at the lumbar
      spine or total hip; serum 25(OH) D levels >=20 ng/mL) were randomized to receive
      one subcutaneous dose of denosumab 60 mg or placebo. All subjects received oral
      calcium >=1000 mg and vitamin D3 >= 400 IU daily. The primary end point was mean
      percent change in bone mineral density (BMD) at the lumbar spine from baseline to
      Month 6. Secondary end points included mean percent change from baseline in BMD
      at total hip, femoral neck, and trochanter at Month 6 and median percent change
      from baseline in bone turnover markers at Months 1, 3, and 6. RESULTS: Total 225
      subjects (denosumab = 111, placebo = 114) completed the six-month study. Baseline
      demographics were similar between groups. A 3.1% (95% confidence interval, 1.9%,
      4.2%) increase favoring denosumab versus placebo was seen for the primary end
      point (P < 0.0001). Denosumab demonstrated a significant treatment benefit over
      placebo for the secondary end points. There were no fractures or withdrawals due
      to adverse events. CONCLUSIONS: Consistent with results from studies conducted in
      other parts of the world, denosumab was well tolerated and effective in
      increasing BMD and decreasing bone turnover markers over a six-month period in
      Indian postmenopausal women.

PMID- 25593844
TI  - Maternal serum biomarkers for risk assessment in gestational diabetes. A
      potential universal screening test to predict GDM status.
AB  - The prevalence of gestational diabetes mellitus (GDM) is increasing because of
      the worldwide obesity/diabetes epidemic. The complications of untreated GDM
      affect both the mother and baby and include complications during pregnancy as
      well as increased risk of subsequent type-2 diabetes in mothers and offspring.
      Standard tests for hyperglycemia in diabetes, such as fasting glucose and
      hemoglobin (HbA1c), are currently not recommended for GDM screening. Instead, an
      oral glucose tolerance test is specified, which is invasive, time-consuming, and
      not easily accessible to many at-risk populations. In this study, we describe a
      multi-analyte maternal serum profile test that incorporates novel glycoprotein
      biomarkers and previously described GDM-associated markers. In screening for GDM
      by multi-analyte panel, the detection rate was 87% at a false-positive rate of
      1%. 

PMID- 25593845
TI  - Assessment of insulin sensitivity/resistance.
AB  - Insulin resistance is one pretty troublesome entity which very commonly
      aggravates metabolic syndrome. Many methods and indices are available for the
      estimation of insulin resistance. It is essential to test and validate their
      reliability before they can be used as an investigation in patients. At present,
      hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the
      most reliable methods available for estimating insulin resistance and are being
      used as a reference standard. Some simple methods, from which indices can be
      derived, have been validated e.g. homeostasis model assessment (HOMA),
      quantitative insulin sensitivity check index (QUICKI). For the clinical uses HOMA
      insulin resistance, QUIKI, and Matsuda are suitable, while HES, McAuley,
      Belfiore, Cederholm, Avignon and Stumvoll index are suitable for
      epidemiological/research purposes. With increasing number of these available
      indices of IR, it may be difficult for clinicians to select the most appropriate
      index for their studies. This review provides guidelines that must be considered
      before performing such studies. 

PMID- 25593846
TI  - Mountford Joseph Bramley: A pioneering thyroidologist and the first principal of
      Asia's oldest medical college.
AB  - Mountford Joseph Bramley was one of the educationists whose sincere efforts are
      undeniable in the making of modern India. After achieving the Member of the Royal
      College of Surgeons diploma, he joined the Malta Garrison as a Hospital Assistant
      and was soon promoted to the rank of Assistant Surgeon of the Rifle Brigade.
      Following his arrival in India in 1826, he held several important medical posts
      in the British service. He was one of the early researchers to investigate the
      role of iodine in the causation of goitre. He was appointed as the first
      Principal of the Medical College of Bengal, the oldest medical college in Asia,
      in 1835. Bramley was an educationist from the very core of his heart, and he
      always wished for the betterment of his students. He died early at the age of 34
      years. His legacy as a pioneer in the fields of medical education and
      endocrinology, specifically thyroidology, has largely been shrouded in a miasma
      of time. 

PMID- 25593847
TI  - A dialogue-based approach to patient education.
AB  - In recent years, the need for person-centered patient education has become
      evident. To translate this approach into practice, new theoretically and
      empirically sound methods and models are required. This brief communication
      introduces a newly developed toolkit that has shown promise in facilitating
      person-centered education and active involvement of patients. Two health
      education models constituting the underlying basis for the toolkit are also
      presented. 

PMID- 25593848
TI  - Endocrine and metabolic disease: Confocal microscopy as a diagnostic aid.
AB  - Diabetes is a systemic disease associated with many complications. These can be
      prevented and managed effectively if detected promptly. Confocal microscopy (CFM)
      is a diagnostic tool which has the potential to help in early detection of
      disease and timely management. CFM has the potential to serve as an excellent
      noninvasive modality for in vivo imaging and morphological analysis, which can
      aid us in assessing and monitoring various infectious and pathological diseases
      at the cellular level. Besides ophthalmological indications, CFM has shown good
      sensitivity and specificity for identifying those at risk of neuropathy and foot
      ulceration, monitoring evolution and therapeutic response in a wide range of
      neuropathies apart from diabetic neuropathy. Through this communication, we aim
      to sensitize the endocrinologists towards cerebral cavernous malformation as a
      biomarker to evaluate potential outcomes and therapies in human diabetic
      neuropathy. 

PMID- 25593849
TI  - Insulin-derived amyloidosis.
AB  - Amyloidosis is the term for diseases caused by the extracellular deposition of
      insoluble polymeric protein fibrils in tissues and organs. Insulin-derived
      amyloidosis is a rare, yet significant complication of insulin therapy. Insulin
      derived amyloidosis at injection site can cause poor glycemic control and
      increased insulin dose requirements because of the impairment in insulin
      absorption, which reverse on change of injection site and/or excision of the
      mass. This entity should be considered and assessed by histopathology and
      immunohistochemistry, in patients with firm/hard local site reactions, which do
      not regress after cessation of insulin injection at the affected site. SEARCH
      STRATEGY: PubMed was searched with terms "insulin amyloidosis". Full text of
      articles available in English was reviewed. Relevant cross references were also
      reviewed. Last search was made on October 15, 2014.

PMID- 25593850
TI  - Development of culturally sensitive dialog tools in diabetes education.
AB  - Person-centeredness is a goal in diabetes education, and cultural influences are
      important to consider in this regard. This report describes the use of a design
      based research approach to develop culturally sensitive dialog tools to support
      person-centered dietary education targeting Pakistani immigrants in Denmark with
      type 2 diabetes. The approach appears to be a promising method to develop dialog
      tools for patient education that are culturally sensitive, thereby increasing
      their acceptability among ethnic minority groups. The process also emphasizes the
      importance of adequate training and competencies in the application of dialog
      tools and of alignment between researchers and health care professionals with
      regards to the educational philosophy underlying their use. 

PMID- 25593852
TI  - Seizure as a presenting manifestation of vitamin D dependent rickets type 1.

PMID- 25593851
TI  - Glucagon-like peptide 1 and dysglycemia: Conflict in incretin science.
AB  - Although GLP-1 (glucagon like peptide-1) based therapies (GLP-1 agonists and
      dipeptidyl peptidase-4 inhibitors) is currently playing a cornerstone role in the
      treatment of type 2 diabetes, dilemma does exist about some of its basic
      physiology. So far, we know that GLP-1 is secreted by the direct actions of
      luminal contents on the L cells in distal jejunum and proximal ileum. However,
      there is growing evidence now, which suggest that other mechanism via "neural" or
      "upper gut" signals may be playing a second fiddle and could stimulate GLP-1
      secretion even before the luminal contents have reached into the proximities of L
      cells. Therefore, the contribution of direct and indirect mechanism to GLP-1
      secretion remains elusive. Furthermore, no clear consensus exists about the
      pattern of GLP-1 secretion, although many believe it is monophasic. One of the
      most exciting issues in incretin science is GLP-1 level and GLP-1 responsiveness.
      It is not exactly known as to what happens to endogenous GLP-1 with progressive
      worsening of dysglycemia from normal glucose tolerance to impaired glucose to
      frank diabetes and furthermore with increasing duration of diabetes. Although,
      conventional wisdom suggests that there may be a decrease in endogenous GLP-1
      level with the worsening of dysglycemia, literature showed discordant results.
      Furthermore, there is emerging evidence to suggest that GLP-1 response can vary
      with ethnicity. This mini review is an attempt to put a brief perspective on all
      these issues. 

PMID- 25593853
TI  - Neonatal thyroid screening: Relationship between cord blood thyroid stimulating
      hormone levels and thyroid stimulating hormone in heel prick sample on 4(th) to
      7(th) day-of-life.

PMID- 25593854
TI  - Cut-offs for stretched penile length in neonates.

PMID- 25593855
TI  - Goiter in Ancient Greek art.

PMID- 25593856
TI  - Bladder dysfunction in women with type 2 diabetes mellitus.

PMID- 25593857
TI  - The nature of surgical education early in the 21(st) century.

PMID- 25593858
TI  - Craniofacial reconstruction and stem cell engineering.

PMID- 25593859
TI  - Three-dimensional computer-aided surgical workflow to aid in reconstruction: From
      diagnosis to surgical treatment.
AB  - The development of three-dimensional computer-aided surgical workflow has
      simplified the planning of complex reconstruction cases. It can also be helpful
      in planning distraction osteogenesis cases. This article examines the evolving
      role of three-dimensional computer-aided surgical workflow in maxillofacial
      surgery. 

PMID- 25593861
TI  - 20 years of cleft lip and palate missions.
AB  - Volunteer missions for cleft lip and palate (CLP) care in Indonesia (1991-1992),
      India (1994-2003), Bhutan (2005-2010), and Kenya (2011), took place always at the
      same Hospital in each country. Altogether over a thousand patients were operated
      using a conservative protocol: Safety first - no experiments. Five months and 5
      kg were the basic rules. For the native doctors, training help for self-help was
      priority. In the announcements, patients with CLP were primarily addressed.
      Burns, contractions, tumors, and trauma-cases were the second priority. Fresh
      trauma was done in night shifts with the local surgeons in order not to
      interfere. Besides facial esthetics speech was the number one issue, following
      priorities fell into place. Cultural aspects played a certain role in the
      different countries and continents. 

PMID- 25593860
TI  - Soft tissue changes and its stability as a sequlae to mandibular advancement.
AB  - PURPOSE OF THE STUDY: To predict the changes and evaluate the stability that
      occurs in the soft tissues following the skeletal movement subsequent to surgical
      advancement of the mandible through bilateral sagittal split osteotomy and to
      provide the patient reliable information with regard to esthetic changes that can
      be expected following the treatment. MATERIALS AND METHODS: Twenty adult patients
      diagnosed with skeletal class II malocclusion and underwent bilateral sagittal
      split osteotomy for mandibular advancement by a mean of 8 mm using rigid fixation
      were included in the study. Soft tissue changes brought about by the surgical
      procedure and their stability over a period of time were evaluated prospectively
      using 12 linear (4 vertical and 8 horizontal) and 4 angular measurements on
      profile cephalograms which were taken preoperatively after the pre-surgical
      orthodontics (T1) and postoperatively with duration of 1 month (T2) and 6 months
      (T3) respectively. RESULTS: It was observed that compared to the linear
      measurements, the angular measurements showed significant changes. The
      improvement in the esthetic outcome is a direct reflection of the angular changes
      whereas the linear changes played a contributing role. Following mandibular
      advancement surgery the profiles of the patients was perceived to have improved
      with reduction in the facial convexity, an increase in the lower facial height,
      decrease in the depth of the mentolabial sulcus and improvement in the lip
      competency with lengthening, straightening and thinning of the lower lip.
      CONCLUSION: The soft tissue response and its stability depends on the stability
      of the surgical procedure itself, postsurgical growth and remodeling of the hard
      tissues and soft tissue changes as a result of maturation and aging.

PMID- 25593862
TI  - Surgical treatment of comminuted mandibular fractures using a low-profile locking
      mandibular reconstruction plate system.
AB  - OBJECTIVE: The treatment of comminuted mandibular fractures is challenging due to
      the severity of associated injuries and the need for a careful diagnosis with
      adequate treatment planning. Recently, open reduction and stable internal
      fixation (OR-IF) with a load-bearing reconstruction plate have been advocated for
      reliable clinical outcomes with minimal complications. This clinical prospective
      study evaluated OR-IF in the surgical management of comminuted mandibular
      fractures with a new low-profile, thin, mandibular locking reconstruction plate.
      MATERIALS AND METHODS: We prospectively assessed OR-IF of comminuted mandibular
      fractures with a low-profile locking mandibular reconstruction plate in 12
      patients (nine men, three women; mean age 32.2 [range 16-71] years) between April
      2010 and December 2011. The clinical characteristics and associated clinical
      parameters of patients were evaluated over a minimum follow-up period of 12
      months. RESULTS: Traffic accidents caused 50% of the fractures, followed by falls
      (25%). Four patients (33.3%) had associated midfacial maxillofacial fractures,
      while five patients had other mandibular fractures. Seven patients (58.3%) needed
      emergency surgery, mostly for airway management. Anatomical reduction of the
      comminuted segments re-established the mandibular skeleton in stable occlusion
      with rigid IF via extraoral (33.3%), intraoral (50%), or combined (16.7%)
      approaches. Immediate functional recovery was achieved. Sound bone healing was
      confirmed in all patients, with no complications such as malocclusion, surgical
      site infection, or malunion with a mean follow-up of 16.3 (range 12-24) months.
      CONCLUSIONS: OR-IF using a low-profile reconstruction plate system is a reliable
      treatment for comminuted mandibular fractures, enabling immediate functional
      recovery with good clinical results.

PMID- 25593863
TI  - Induction of multinucleated giant cells in response to small sized bovine bone
      substitute (Bio-OssTM) results in an enhanced early implantation bed
      vascularization.
AB  - PURPOSE: The host tissue reaction to the xenogeneic bone substitute Bio-OssTM
      (Geistlich Biomaterials, Wolhousen, Switzerland) was investigated focusing on the
      participating inflammatory cells and implantation bed vascularization. MATERIALS
      AND METHODS: Bio-OssTM was implanted subcutaneously into CD1 mice for up to 60
      days and analyzed by means of specialized histological and histomorphometrical
      techniques after explantation. RESULTS: Bio-OssTM induced within the first 15
      days an early high vascularization combined with a marked presence of
      multinucleated giant cells. The latter cells were associated mainly with the
      smaller sized granules within the implantation bed. Toward the end of the study
      the number of multinucleated giant cells decreased while the tissue reaction to
      the larger granules was mainly mononuclear. CONCLUSION: The results of the
      present study showed that smaller xenogeneic bone substitute granules induce
      multinucleated giant cells, whereas the larger-sized ones became integrated
      within the implantation bed by means of a mononuclear cell-triggered granulation
      tissue. Obviously, the presence of multinucleated giant cells within biomaterial
      implantation beds is not only related to the type of synthetic bone substitute
      material, but also to the granule size of the natural-based xenogeneic bone
      substitute material.

PMID- 25593865
TI  - Biomechanical comparison of two intraoperative mobilization techniques for
      maxillary distraction osteogenesis: Down-fracture versus non-down-fracture.
AB  - PURPOSES: The purpose of this study was to compare the distraction forces and the
      biomechanical effects between two different intraoperative surgical procedures
      (down-fracture [DF] and non-DF [NDF]) for maxillary distraction osteogenesis.
      MATERIALS AND METHODS: Eight patients were assigned into two groups according to
      the surgical procedure: DF, n = 6 versus NDF, n = 2. Lateral cephalograms taken
      preoperatively (T1), immediately after removal of the distraction device (T2),
      and after at least a 6 months follow-up period (T3) were analyzed. Assessment of
      distraction forces was performed during the distraction period. The Mann-Whitney
      U-test was used to compare the difference in the amount of advancement, the
      maximum distraction force and the amount of relapse. RESULTS: Although a
      significantly greater amount of maxillary movement was observed in the DF group
      (median 9.5 mm; minimum-maximum 7.9-14.1 mm) than in the NDF group (median 5.9
      mm; minimum-maximum 4.4-7.6 mm), significantly lower maximum distraction forces
      were observed in the DF (median 16.4 N; minimum-maximum 15.1-24.6 N) than in the
      NDF (median 32.9 N; minimum-maximum 27.6-38.2 N) group. A significantly greater
      amount of dental anchorage loss was observed in the NDF group. Moreover, the
      amount of relapse observed in the NDF group was approximately 3.5 times greater
      than in the DF group. CONCLUSIONS: In this study, it seemed that, the use of the
      NDF procedure resulted in lower levels of maxillary mobility at the time of the
      maxillary distraction, consequently requiring greater amounts of force to advance
      the maxillary bone. Moreover, it also resulted in a reduced amount of maxillary
      movement, a greater amount of dental anchorage loss and poor treatment stability.

PMID- 25593864
TI  - Acellular dermal matrix allograft: An effective adjunct to oronasal fistula
      repair in patients with cleft palate.
AB  - CONTEXT: Oronasal fistula (ONF) following cleft palate (CP) repair are a
      challenging problem associated with high recurrent rates. Acellular dermal matrix
      allograft is an available tissue substitute. AIMS: The aim of this study was to
      evaluate the effectiveness of acellular dermal matrix in the repair of ONF
      associated with CP that is recurrent or larger than 15 mm in any dimension.
      SETTINGS AND DESIGN: This is a prospective study where 12 patients with repaired
      CP suffering from ONF of the hard palate >15 mm in diameter were included.
      MATERIALS AND METHODS: Age ranged from 12 to 25 years. Acellular dermal matrix
      was firmly secured between repaired oral and nasal mucosal layers. Patients were
      clinically followed-up for 6 months postoperatively to assess total time for
      complete healing, dehiscence and/or refistulaization. STATISTICAL ANALYSIS USED:
      Fisher's exact test. RESULTS: Acellular dermal matrix was integrated with
      successful fistula closure in all except 1 patient where failure of graft
      integration was noticed early postoperatively. In 6 patients, the oral mucosal
      layer showed dehiscence, through which the graft was exposed. Graft integration
      extended from 4 to 12 weeks postoperatively during which patients were instructed
      to follow a soft diet and meticulous oral hygiene measures. CONCLUSIONS:
      Acellular dermal matrix allografts are safe and effective adjuncts for use in
      closure of ONF in the hard palate that is recurrent or larger than 15 mm in any
      dimension.

PMID- 25593866
TI  - Quantitative validation of a computer-aided maxillofacial planning system,
      focusing on soft tissue deformations.
AB  - AIM: The aim of this study was to evaluate the accuracy of 3D soft tissue
      predictions generated by a computer-aided maxillofacial planning system in
      patients undergoing orthognathic surgery. METHODS AND MATERIALS: Twenty patients
      with dentofacial dysmorphosis were treated with orthognathic surgery after a
      preoperative orthodontic treatment. Fourteen patients had an Angle Class II
      malocclusion; three patients had an Angle class III malocclusion, and three
      patients had an Angle Class I malocclusion. Skeletal asymmetry was observed in
      six patient. The surgeries were planned using the Maxilim software. Computer
      assisted surgical planning was transferred to the patient by digitally generated
      splints. The validation procedures were performed in the following steps: (1)
      Standardized registration of the pre- and postoperative Cone Beam CT volumes; (2)
      Automated adjustment of the bone-related planning to the actual operative bony
      displacement; (3) Simulation of soft tissue changes; (4) Calculation of the soft
      tissue differences between the predicted and the postoperative results by
      distance mapping. STATISTICAL ANALYSIS AND RESULTS: Eighty four percent of the
      mapped distances between the predicted and actual postoperative results measured
      between -2 mm and +2 mm. The mean absolute linear measurements between the
      predicted and actual postoperative surface was 1.18. Our study shows the overall
      prediction was dependent on neither the surgical procedures nor the dentofacial
      deformity type. CONCLUSION: Despite some shortcomings in the prediction of the
      final position of the lower lip and cheek area, this software promises a
      clinically acceptable soft tissue prediction for orthognathic surgical
      procedures.

PMID- 25593867
TI  - Analgesic efficacy of acetaminophen for controlling postextraction dental pain.
AB  - BACKGROUND: Considering the clinical safety of acetaminophen over other
      nonsteroidal anti-inflammatory drugs, this clinical trial was formulated to
      assess the analgesic efficacy of acetaminophen for controlling postextraction
      dental pain when compared to commonly prescribed ibuprofen. AIM: The aim was to
      assess the analgesic efficacy of paracetamol/acetaminophen in postextraction
      dental pain. SETTINGS AND DESIGN: Double-blind, randomized prospective clinical
      trial. MATERIALS AND METHODS: A total of 30 patients requiring bilateral
      maxillary and mandibular premolar extraction for their orthodontic treatment were
      included in the study to evaluate the efficacy of acetaminophen in controlling
      postextraction dental pain. STATISTICAL ANALYSIS USED: Unpaired t-test. RESULTS
      AND CONCLUSIONS: Clinically, both the postoperative analgesics exerted similar
      pain control with minor variations of recorded visual analog scale scores by the
      patients in both the groups. It may be concluded from the findings of this study
      that paracetamol at a dosage of 500 mg thrice a day (1.5 g) is sufficient to
      achieve reliable pain control following exodontia provided the surgical trauma
      caused to the investing tissues is minimal.

PMID- 25593868
TI  - A retrospective study of patients with mandibular fractures treated at a Swedish
      University Hospital 1999-2008.
AB  - BACKGROUND: Fracture of the mandible is one of the most common fractures of the
      maxillofacial skeleton. However, the etiology, gender, and age distribution vary
      between different regions and countries, and the purpose of this study was to
      evaluate the current trend of patients with mandibular fractures at the
      Department of Oral and Maxillofacial Surgery, in Uppsala, Sweden. AIM: The aim of
      this retrospective study was to analyze patients with mandibular fractures
      treated in the University Hospital of Uppsala (the county capital of Uppland)
      Sweden during a 10-year period (1999-2008). MATERIALS AND METHODS: This study was
      designed as a retrospective study of patients admitted to the Department of Oral
      and Maxillofacial Surgery at Uppsala University Hospital, Sweden. The location of
      fractures was evaluated clinically by the surgeon and on the X-rays. We
      classified the data according to gender, age, etiology, day of the week, month of
      the year, fracture site, and method of treatment of the fractures. RESULTS:
      Records were collected from patient charts from 266 patients. One hundred eighty
      seven patients (70%) with mandibular fractures were of male gender, and 132
      patients (50%) were aged 16-30 years. Interpersonal violence constituted the most
      common etiological factor for mandibular fractures (24%), followed by falls
      (23%). Forty-nine percentages of the patients were treated surgically, and 51%
      were treated conservatively. There was an increase of the annual incidence of
      fractures toward the end of the period, even though not statistically
      significant. CONCLUSIONS: Mandibular fractures occurred primarily among younger
      men between 16- and 30-year-old. Condyle fractures were the most common fracture
      site and 50% of the patients required surgery. Summer months and weekends were
      the most common time of mandibular fractures.

PMID- 25593869
TI  - Cleft-Rhinoplasty constricted nasal floor reconstruction.
AB  - INTRODUCTION: Widening of alar base width is often required in the postcleft
      lip/palate rehabilitation. This manuscript aims to present the author's design
      for such a procedure describing the qualitative outcome of such a correction.
      MATERIALS AND METHODS: This is a retrospective study from the author's center.
      All cleft cases requiring alar base widening using author's approach were
      analysed, and the outcome presented at the baseline, end of 3(rd) and 6(th)
      month. Author used a typical superomedially placed nasolabial full thickness flap
      to correct the alar base width simultaneously replacing the nasal lining.
      RESULTS: A total of nine cleft patients underwent the procedure. Qualitative
      observation of the outcomes and postoperative changes with the resultant nasal
      alar base width are presented. DISCUSSION: The efficacy of this type of
      nasolabial flap for the alar basal widening and nasal lining reconstruction is
      presented. The esthetical, functional and anatomical consideration in such a flap
      design is presented with the experience gained from this cohort.

PMID- 25593870
TI  - Modified basal osteotomy combined with osteogenic distraction (Hemi-Wing
      distraction) for correction of facial asymmetry: A new technique.
AB  - Complete restoration of facial asymmetry is always difficult to achieve. Facial
      asymmetry due to growth disturbances of the jaws almost requires orthognathic
      surgical correction, followed, in many cases, by soft tissue corrections.
      Mandibular hypoplasia is the earliest skeletal manifestation of Hemifacial
      microsomy and the clinical defect becomes worse with the time, due to asymmetric
      growth and secondary midface deformity accompanying. Despite correction of the
      occlusal plane, facial asymmetry can persist if the mandibular body differs in
      height. We designed a new technique for skeletal correction of the mandibular
      basal plane combined with orthognatic surgery that avoided the disadvantages and
      limitations of other techniques. A 20-year-old male patient with facial asymmetry
      due to Hemifacial microsomy Type I also requires preoperative orthodontic
      treatment to align and level their teeth. He showed a 2mm midline shift to the
      left in combination with a cross bite of the left side. We decide to do a
      vertical enlargement of the mandibular left border by mandibular Hemiwing
      osteotomy and unilateral split ramus osteotomy for dental lines alignment with 8
      mm of advancement of the hemi - wing genioplasty. Modificated basal osteotomy
      combined with osteogenic distraction works better than the classic total basal
      osteotomy with autologous bone graft, if used for the correct indications. We
      advocate this technique for its efficacy, simplicity, and safety. This technique
      can be apply for correction of vertical and transverse discrepancies of the
      mandibular border and combined with sagittal ramus osteotomies for correction of
      asymmetrical dental lines and oclusal plane. 

PMID- 25593871
TI  - Treatment of osteoradionecrosis of mandible with bone marrow concentrate and with
      dental pulp stem cells.
AB  - Osteoradionecrosis (ORN) is a noninfectious, necrotic condition of the bone
      occurring as a complication of radiotherapy. Most cases occur following trauma or
      surgical manipulation of the irradiated site. Mandible is the most common bone to
      be affected following head and neck irradiation. The aim was to develop a
      successful therapeutic approach for ORN. A spectrum of treatment modalities is
      practiced for ORN with variable success rate that includes simple irrigation of
      the affected bone to the partial or complete resection of the jaw bone. In this
      paper, we present two cases which had successful therapeutic approach for ORN of
      mandible with autologous bone marrow concentrate stem cells and allogeneic dental
      pulp stem cells (DPSC) with platelet rich plasma (PRP) following failure of
      conventional methods. Autologous bone marrow aspirate concentrate (BMAC) was
      injected around the socket and into the periosteum for one case, and DPSC were
      mixed with tricalcium phosphate and inserted at the site of the defect in one
      case. The patient treated with BMAC remained asymptomatic and complete bone
      remodeling was noticed after 1 year. The extraoral sinus was excised, and healing
      was uneventful without recurrence in the patient treated with allogeneic DPSC and
      PRP. Periodic panoramic radiographs revealed an appreciable bone formation from
      the 2(nd) month onward. We have successfully treated two cases of ORN with BMAC
      and DPSC, respectively. 

PMID- 25593872
TI  - Supernumerary nostril: Congenital adrenal hyperplasia with a rare congenital
      anomaly.
AB  - Multiple or supernumerary nostril is a rare congenital anomaly with unknown
      etiology. The first case was reported by Lindsay as bilateral supernumerary
      nostrils. Supernumerary nostril cases are mostly unilateral and isolated. They
      are also reported with other congenital malformations like facial clefts and
      congenital anomalies like congenital auricular hypoplasia, congenital cataracts,
      eusophageal atresia and patent ductus arteriosus. Here, we report a case of
      supernumerary nostril with congenital adrenal hyperplasia. 

PMID- 25593873
TI  - Frontoethmoidal encephalocele: Case report and review on management.
AB  - Encephaloceles, especially in the frontoethmoidal region, are a form of neural
      tube defect affecting patients in Southeast Asia more commonly than those in
      western countries, where they are more common in the occipital regions. All
      patients with classical frontoethmoidal encephalocele had swelling over the
      bridge of nose or inner canthus of eye since birth, with varying degrees of
      hypertelorism. This paper emphasizes on the clinical features of this pathology
      and its surgical management, along with, reviewing the evolution of single-stage
      correction and fine refinements. 

PMID- 25593874
TI  - Protein-signaled guided total jaw regeneration in infantile total mandibular
      resection.
AB  - Maxillofacial reconstruction on a young child with huge aggressively growing
      lesion is a tough situation owing to several limiting factors. Besides the other
      factors, impact of the growing lesion on the psychology of the child also needs
      to be considered. This manuscript reports a case of an 18-month-old boy with
      juvenile cemento-ossifying fibroma in whom removal of a large portion of the jaws
      was required. The regeneration of the jaw bones with the help of protein signal
      guided reconstruction using bone morphogenetic protein-2 is described. Long-term
      follow-up of the patient with dental implants placed on the neo-osteogenic bone
      is reported. 

PMID- 25593875
TI  - Pseudoaneurysm of the internal maxillary artery following mandibular condylar
      fracture.
AB  - Pseudoaneurysm of the internal maxillary artery is a rare occurrence. A well
      organized pulsatile mass that develops after a traumatic event indicates a
      pseudoaneurysm. Such lesions are commonly misdiagnosed for an abscess or a
      hematoma. Pulsations and audible bruit are diagnostic features of an aneurysm.
      Rupture of such false aneurysms cause significant morbidity. Management is either
      surgical resection or embolization. Endovascular embolization is indicated in
      deep seated lesions or lesions with high morbidity. Though surgical resection is
      an invasive procedure, it is considered to be an alternative to embolization. 

PMID- 25593876
TI  - Maxillary sinus perforation with presence of an antral pseudocyst, repaired with
      platelet rich fibrin.
AB  - The maxillary sinus lifting procedure is an important preprosthetic surgical
      procedure for the creation of adequate bone volume in the edentulous posterior
      maxilla for the placement of dental implants. The presence of a maxillary sinus
      cyst has been considered a contraindication for this operation. Perforation of
      the membrane and hence the elongation of the healing time for implant placement
      is the most common complication in this type of procedure. The purpose of the
      case is to show the safely repair of the large sinus perforation during the sinus
      lifting with presence of the antral pseudocyst. In this case, we present a
      patient who had a maxillary sinus lifting procedure in the presence of antral
      pseudocysts. No complications were seen during follow-up periods and all implants
      are functioning successfully. Platelet-rich fibrin may be used safely when large
      perforation occurs during the sinus lifting with the presence of an antral
      pseudocyst. 

PMID- 25593877
TI  - Pseudo-ankylosis caused by osteoma of the coronoid process.
AB  - Osteoma of the coronoid process is a rare, slow-growing tumor that can lead to
      restrictive mandibular movements. This paper describes a case of osteoma of the
      right coronoid process in a 45-year-old woman who reported progressive facial
      asymmetry and the loss of mandibular movements. Aspects regarding the
      differential diagnosis, treatment, surgical access, possible complications and
      postoperative follow up of the case are also discussed. The osteoma of the
      coronoid process is a benign tumor that can reach a significant size, causing an
      increase in volume, facial asymmetry, limited mouth opening and fracture of the
      zygomatic complex in some cases. The combination of extraoral and intraoral
      accesses is useful in the case of large tumors of difficult access, such as in
      this case reported. 

PMID- 25593878
TI  - Giant odontogenic fibroma of maxilla.
AB  - Odontogenic fibroma is a benign ectomesenchymal tumor classified as central and
      peripheral on the basis of its location and as an epithelium rich or epithelium
      poor based on its histological features. Radiological findings consist of
      radiolucent areas with well-defined bony margins. The lesion is detected early
      because of its location and usually treated with surgical excision and curettage.
      We present a case of giant odontogenic fibroma of right maxilla presenting as
      gross facial deformity and posing a dual challenge of excising the tumor mass and
      reconstructing the ensuing defect. 

PMID- 25593879
TI  - Osteochondroma of the mandibular condyle: Report of two surgical approaches.
AB  - Osteochondromas are common tumors of the long bones, but are rare in the
      craniofacial region. We detailed two different management of osteochondroma of
      the mandibular condyle treated utilizing three-dimensional (3D) imaging and
      computer-assisted planning. Simultaneous open temporomandibular joint and
      orthognathic surgeries were done to treat both the pathology and secondary facial
      asymmetry. An osteochondroma that presented as a bony mass at the lateral aspect
      of the left mandibular condyle of a 24-year-old Chinese female was treated with
      simultaneous orthognathic surgery and conservative excision. No recurrence was
      detected 7 months postsurgery. An osteochondroma that presented as a generalized
      enlargement of the right mandibular condyle of a 25-year-old Chinese male was
      treated with simultaneous orthognathic surgery and condylectomy. There were no
      significant issues 3 years postsurgery. Simultaneous orthognathic and
      temporomandibular joint surgeries are a viable option for the management of
      osteochondroma of the mandibular condyle. The availability of 3D imaging enabled
      better presurgical examination of the lesion, which directed treatment toward
      condylectomy or conservative excision. 

PMID- 25593880
TI  - True chondroma of the mandibular condyle: A rare case.
AB  - Chondroma of the mandibular condyle is a rare benign tumor, with just a handful
      of cases reported in the literature. Chondromas are rare in the maxillofacial
      region, but are quite common in the bones of the hands and feet. So far only
      eight cases of true chondroma have been reported. Here, we present a case of true
      chondroma of the mandibular condyle of the right side, for which condylectomy was
      done. No signs of recurrence are noted at 2 years follow-up. 

PMID- 25593881
TI  - Ancient schwannoma of the infratemporal fossa.
AB  - Schwannomas are benign tumors of neurogenic origin arising from the Schwann cells
      of peripheral, cranial, and autonomic nerves. Schwannomas in spite of
      constituting 25-40% of head and neck tumors the percentage of intraoral
      schwannomas is merely 1%. Among the intraoral schwannoma the occurrence of the
      variant "ancient schwannoma of the infratemporal fossa with an intraoral
      presentation is very rare. The purpose of this presentation is to highlight the
      rarity of this lesion, to stress the importance of an accurate diagnosis and to
      consider neurogenic lesions in the differential diagnosis of head and neck
      lesions. 

PMID- 25593882
TI  - Inflammatory myofibroblastic tumor of the upper alveolus: A rare entity
      presenting as a jaw swelling.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare tumor of borderline nature
      that can clinically present as a malignant neoplasm. It commonly occurs in the
      lungs, and a very few oral IMTs have been reported in the literature. IMT
      consists of inflammatory cells and myofibroblastic spindle cells. The diagnosis
      of IMT requires histopathological examination with immunohistochemical staining
      to look for the expression of smooth-muscle actin for confirmation of the
      diagnosis. The objective of this paper is to report an IMT on the upper alveolus
      with clinic-a pathological similarity with a malignant lesion and its management.
      Though oral IMTs are rare, it should be considered in the differential diagnosis
      of tumors of the upper jaw. Complete surgical excision of alveolar IMT is the
      treatment of choice because of its unpredictable clinical behavior. The patients
      with oral IMTs require periodic post-surgical follow-up for recurrence. 

PMID- 25593883
TI  - A rare cause of lateral facial swelling.
AB  - A case of chronic, recurrent and asymptomatic facial swelling in a young male is
      presented. Swelling extended from lower midface to upper lateral neck and right
      commissure to anterior massetric border. History, clinical signs and symptoms and
      examination pointed towards the benign nature of the swelling. Fine-needle
      aspiration cytology tapered the diagnostic possibilities to a salivary cyst or
      pseudocyst. Ultrasonography identified the lesion to contain echogenic fluid with
      irregular borders. "Tail sign" was absent on contrast magnetic resonance imaging,
      excluding the involvement of the sublingual gland. Surgical excision of the
      lesion was done along with submandibular gland as both were in continuity via a
      bottle-neck tract. Final histopathological diagnosis was that of the
      submandibular gland extravasation phenomenon. As per the best of our knowledge,
      it is the first case report of a submandibular gland extravasation causing
      swelling in a retrograde direction onto the face. 

PMID- 25593884
TI  - Two rare cases of rhinosporidiosis of parotid duct: Case reports and review of
      literature.
AB  - Rhinosporidiosis is a chronic granulomatous infective disease caused by fungi,
      Rhinosporidium seeberi. It can occur universally, is endemic in India, Sri Lanka
      and in South Asia, mainly reported from Southern India and Sri Lanka.
      Rhinosporidiosis is a chronic disease classically involving nose and nasopharynx
      and presents as a localized polypoid mass. Rhinosporidiosis involving parotid
      duct is rare. We encountered two cases of rhinosporidiosis at extremely unusual
      extranasal site-parotid duct, presenting as a cyst without nasal manifestations,
      which was misdiagnosed clinically and on cytological examination. 

PMID- 25593885
TI  - Distraction osteogenesis of free flap reconstructed mandible following
      ameloblastoma resection for optimal functional rehabilitation.
AB  - This case highlights the use of a custom-made distractor (Synthes GmbH, Oberdorf,
      Switzerland), used to increase bone height prior to rehabilitation with implant
      placement, in a patient following excision of an ameloblastoma and reconstruction
      of her mandible with a fibular flap. A 27-year-old patient had her mandible
      reconstructed following wide resection of an ameloblastoma. Although a 2.0 LOCK
      reconstruction plate (Synthes GmbH, Oberdorf, Switzerland) was used for fixation
      of the fibular bone, the vertical deficiency between the reconstructed segment
      and the occlusal plane made oral rehabilitation impossible. To overcome this, the
      fibular bone segment was vertically distracted following a latency period of 4
      days. Distractor was left in place for 20 weeks for bone consolidation. Following
      device removal implants were placed. The novelty of this approach included
      fixation of the lower arm of the distractor on the LOCK plate. The distractor was
      unidirectional with two arms of different length. The lower arm composed of a 2.0
      mini-plate to fit exactly on the 2.0 LOCK plate whereas the upper arm used a
      standard 1.5 mini-plate. Advantages of this custom-made distractor included: (i)
      No need for removal of the reconstruction plate, (ii) no need for an extraoral
      surgical approach, and (iii) no need for additional drilling to fit the lower arm
      of the distractor. Technical details and limitations are presented. 

PMID- 25593886
TI  - Alveolar soft part sarcoma of tongue in 14-year-old boy.
AB  - Alveolar soft part sarcoma (ASPS) is a rare, aggressive malignancy of uncertain
      histological origin with propensity of vascular invasion and distant metastasis.
      ASPS demonstrates strong predilection for adolescents and young adults with a
      female preponderance. The head and neck region is the commonly affected region in
      the pediatric population with orbit and tongue being most common. The indolent
      clinical course and asymptomatic nature often leads to misdiagnosis and delayed
      treatment. Herein, we present a case of ASPS affecting the tongue in 14-year-old
      boy which clinically mimicked hemangioma, common benign vascular tumor of tongue.

PMID- 25593887
TI  - Management of craniofacial osteitis deformans.
AB  - Paget's disease of bone (PDB) is a progressive chronic disease of unknown
      etiology, manifested as initial increase in bone resorption, followed by a
      disorganized and excessive formation of bone, resulting in pain and skeletal
      deformities. Treatment of the disease primarily aims at reducing the altered bone
      turnover by pharmacotherapy, along with surgical intervention for deformed bones,
      to reduce morbidity and improve the quality of living. We present a case of PDB
      with craniofacial involvement in a 55-year-old female, diagnosed on the basis of
      clinical features, radiological assessment along with biochemical findings and
      histopathological report. Our management included medical treatment in the form
      of intravenous bisphosphonates which alleviated symptoms by reducing the abnormal
      bone activity, and normalized serum alkaline phosphatase. Patient morale, self
      confidence and social acceptance were all boosted due to the surgical correction
      of the facial deformity. 

PMID- 25593888
TI  - Visual loss due to paranasal sinus invasive aspergillosis in a diabetic patient.
AB  - Aspergillus species are commonly found in the soil and decaying organic matter.
      The spores can be typically inhaled or ingested, yet disease due to tissue
      invasion is rarely seen in the immunocompetent host. In the immunocompromised
      patient, there has been an increased incidence of invasive aspergillosis in the
      last 20 years. Invasive aspergillosis of the maxillary sinus with orbital and
      cranial spread can be lethal, therefore, necessitates early diagnosis and prompt
      treatment. The predilection of Aspergillus for infiltration of blood vessels can
      result in serious ocular complications which can lead to loss of vision. We
      present the case of an uncontrolled diabetic patient with invasive maxillary
      sinus aspergillosis and extension to the orbital contents. Our purpose was to
      emphasize the need of early recognition and prompt initiation of combined
      antifungal treatment and surgical intervention with the intent to preserve the
      involved vital structures. 

PMID- 25593889
TI  - The hanoi declaration.

PMID- 25593890
TI  - Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine
      Dependent Female Rats.
AB  - BACKGROUND: Aloe vera is a medicinal herb used as an anti-inflammatory and
      sedative agent. OBJECTIVES: The current study aimed to evaluate the effect of
      Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent
      female rats. PATIENTS AND METHODS: The current research was performed on 40
      female Wista-Albino rats which were made dependent on morphine using Houshyar
      protocol and were randomly divided into five groups (A, B, C, D, and E). Group A
      did not receive any agent in the period of handling but other groups (B, C, D and
      E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three
      times daily for a week, respectively. Withdrawal symptoms, stool form, agitation,
      disparity, floppy eyelids, and body mass variations were checked for 10 days. The
      obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal
      Wallis, and Mann-Whitney statistical tests. Statistical difference was considered
      significant (P < 0.05). RESULTS: The results of the present study showed that
      agitation, disparity, and floppy eyelids in group E were significantly higher
      than those of others groups; however, these symptoms in group C were
      significantly lower than those of the other groups. CONCLUSIONS: The results of
      the present study revealed that the Aloe vera aqueous extract had various effects
      on morphine withdrawal syndrome in morphine-dependent female rats .

PMID- 25593891
TI  - Is Knowledge Enough? Considering HIV/AIDS Risk Behaviors and HIV/AIDS Knowledge
      with African American Women.
AB  - BACKGROUND: This quantitative explanatory study was designed to explain the
      relationship between HIV/AIDS risk-taking behaviors among African American women
      and their knowledge surrounding HIV/AIDS. More specifically, the research
      considers whether knowledge alone was sufficient to alter African-American
      women's risk-taking behaviors regarding HIV/AIDS. OBJECTIVES: This study was
      designed to investigate knowledge surrounding sexual risk-taking behaviors
      including 1) heterosexual transmission; 2) low and sporadic condom usage; 3)
      illicit drug use; and 4) multiple sex partners associated with HIV positive and
      negative status among African-American women. PATIENTS AND METHODS: Participants
      in this study were African-American women who ranged in age between 24 and 44
      years. This sample of African-American women was divided into two groups
      according to their HIV status: 53 women who were HIV positive and 62 women who
      were HIV negative women. The data for this investigation were obtained through
      self-administered questionnaires. The t-test was used to analyze the data through
      the use of the windows version of the statistical package for social sciences
      (19.0). RESULTS: Findings suggest that knowledge of HIV was not found to be
      significantly different for the HIV positive and negative groups, and thus,
      suggest that knowing about the consequences of risk-taking behaviors is not
      sufficient to alter one's behavior among African American women. The findings
      from this investigation will contribute new empirical knowledge to the existing
      social work database on HIV/AIDS and knowledge specifically relative to African
      American women. CONCLUSIONS: It was anticipated that knowledge of HIV would have
      been significantly higher in the HIV negative group than in the HIV positive
      group. However, the hypothesis was not supported by data. The HIV positive women
      and negative women were equally knowledgeable about HIV/AIDS.

PMID- 25593892
TI  - Attitude to substance abuse: do personality and socio-demographic factors matter?
AB  - BACKGROUND: Substance abuse is a serious global problem that is affected by
      multiple psychosocial and socio-demographic factors. OBJECTIVES: This study aimed
      to investigate the leading factors in positive attitude and tendency toward
      substance abuse in terms of personality, socio-economic, and socio-demographic
      factors. PATIENTS AND METHODS: In a cross-sectional study, 200 college students
      (105 females and 95 males) residing in Damghan University dormitory in northeast
      of Iran were recruited by random sampling from March to July 2013. The
      participants were instructed and asked to complete the NEO FIVE-factor Inventory,
      the attitude to substance abuse scale, and the demographic questionnaire. Then
      data were analyzed by stepwise multiple regression employing PASW 18. RESULTS:
      Being male sex and neuroticism had a significant positive role in predicting
      positive attitude toward substance abuse in university students. In addition,
      agreeableness, conscientiousness, openness, and socio-economic status had a
      significant negative role in predicting tendency toward substance abuse (P <
      0.001). Extraversion had no significant role in prediction of positive attitude
      to substance abuse (P > 0.05). CONCLUSIONS: Lower agreeableness, decreased
      conscientiousness, higher neuroticism, diminished openness, low socio-economic
      status, and male sex might make university students more inclined to substance
      abuse. Thus, it is reasonable to show the importance of these factors in tailored
      prevention programs.

PMID- 25593893
TI  - Early maladaptive schemas in development of addictive disorders as parts of the
      complex addiction jigsaw.

PMID- 25593894
TI  - Religiosity and preventing risky behaviors.

PMID- 25593895
TI  - Analgesic effects of gabapentin and diclofenac on post-operative pain in patients
      undergoing tonsillectomy.

PMID- 25593896
TI  - Split fracture: a complication of cerclage wiring of acute patellar fracture.
AB  - INTRODUCTION: Iatrogenic patellar fracture is reported as a complication of
      patella procedures, such as medial patellofemoral ligament reconstruction,
      reconstruction of the anterior cruciate ligament of the knee using bone-patellar
      tendon-bone technique, and resurfacing the patella in total knee arthroplasty.
      CASE PRESENTATION: A 65-year-old lady with right patella fracture was treated
      with open reduction and cerclage wiring. An iatrogenic split fracture was noted
      during tension of the cerclage wire and was successfully managed by screw
      fixation of the split fracture. CONCLUSIONS: Split fracture is a rare
      complication of circumferential cerclage wiring of patellar fracture. The surgeon
      should be aware of the contributing factors in order to avoid this complication.

PMID- 25593897
TI  - The transforming face of fracture epidemiology.

PMID- 25593898
TI  - New serum biomarkers for prostate cancer diagnosis.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is currently used as a biomarker for
      diagnosis and management of prostate cancer (CaP). However, PSA typically lacks
      the sensitivity and specificity desired of a diagnostic marker. OBJECTIVE: The
      goal of this study was to identify an additional biomarker or a panel of
      biomarkers that is more sensitive and specific than PSA in differentiating benign
      versus malignant prostate disease and/or localized CaP versus metastatic CaP.
      METHODS: Concurrent measurements of circulating interleukin-8 (IL-8), Tumor
      necrosis factor-alpha (TNF-alpha) and soluble tumor necrosis factor-alpha
      receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with
      elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx)
      (3) with clinically localized CaP and (4) with castration resistant prostate
      cancer. RESULTS: TNF-alpha Area under the receiver operating characteristic curve
      (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs.
      CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC
      = 0.997). The strongest single predictors of localized versus metastatic CaP were
      TNF-alpha (AUC = 0.992) and PSA (AUC = 0.963) levels. CONCLUSIONS: The
      specificity and sensitivity of a PSA-based CaP diagnosis can be significantly
      enhanced by concurrent serum measurements of IL-8, TNF-alpha and sTNFR1. In view
      of the concerns about the ability of PSA to distinguish clinically relevant CaP
      from indolent disease, assessment of these biomarkers in the larger cohort is
      warranted.

PMID- 25593899
TI  - Are probiotics or prebiotics useful in pediatric irritable bowel syndrome or
      inflammatory bowel disease?
AB  - Treatment options for irritable bowel syndrome (IBS) and inflammatory bowel
      disease (IBD) are notoriously either inadequate (IBS) or loaded with potentially
      serious side effects and risks (IBD). In recent years, a growing interest in
      effective and safer alternatives has focused on the potential role of probiotics
      and their metabolic substrates, prebiotics. It is in fact conceivable that the
      microbiome might be targeted by providing the metabolic fuel needed for the
      growth and expansion of beneficial microorganisms (prebiotics) or by
      administering to the host such microorganisms (probiotics). This review presents
      a concise update on currently available data, with a special emphasis on
      children. Data for prebiotics in IBS are scarce. Low doses have shown a
      beneficial effect, while high doses are counterproductive. On the contrary,
      several controlled trials of probiotics have yielded encouraging results. A meta
      analysis including nine randomized clinical trials in children showed an
      improvement in abdominal pain for Lactobacillus GG, Lactobacillus reuteri DSM
      17938, and the probiotic mixture VSL#3. The patients most benefiting from
      probiotics were those with predominant diarrhea or with a post-infectious IBS. In
      IBD, the use of prebiotics has been tested only rarely and in small scale
      clinical trials, with mixed results. As for probiotics, data in humans from about
      three dozens clinical trials offer mixed outcomes. So far, none of the tested
      probiotics has proven successful in Crohn's disease, while in ulcerative colitis
      a recent meta-analysis on 12 clinical trials (1 of them in children) showed
      efficacy for the probiotic mixture VSL#3 in contributing to induce and to
      maintain remission. It is evident that this is a rapidly evolving and promising
      field; more data are very likely to yield a better understanding on what strains
      should be used in different specific clinical settings and in what doses. 

PMID- 25593901
TI  - Helicobacter pylori: A Beneficial Gastric Pathogen?

PMID- 25593900
TI  - Intestinal epithelium in inflammatory bowel disease.
AB  - The intestinal epithelium has a strategic position as a protective physical
      barrier to luminal microbiota and actively contributes to the mucosal immune
      system. This barrier is mainly formed by a monolayer of specialized intestinal
      epithelial cells (IECs) that are crucial in maintaining intestinal homeostasis.
      Therefore, dysregulation within the epithelial layer can increase intestinal
      permeability, lead to abnormalities in interactions between IECs and immune cells
      in underlying lamina propria, and disturb the intestinal immune homeostasis, all
      of which are linked to the clinical disease course of inflammatory bowel disease
      (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis
      might contribute to an improved knowledge of the inflammatory processes and the
      identification of potential therapeutic targets. 

PMID- 25593902
TI  - Patterns of circulating inflammatory biomarkers in older persons with varying
      levels of physical performance: a partial least squares-discriminant analysis
      approach.
AB  - BACKGROUND: Chronic, low-grade inflammation and declining physical function are
      hallmarks of the aging process. However, previous attempts to correlate
      individual inflammatory biomarkers with physical performance in older people have
      produced mixed results. Given the complexity of the inflammatory response, the
      simultaneous analysis of an array of inflammatory mediators may provide more
      insights into the relationship between inflammation and age-related physical
      function decline. This study was designed to explore the association between a
      panel of inflammatory markers and physical performance in older adults through a
      multivariate statistical approach. METHODS: Community-dwelling older persons were
      categorized into "normal walkers" (NWs; n = 27) or "slow walkers" (SWs; n = 11)
      groups using 0.8 m s(-1) as the 4-m gait speed cutoff. A panel of 14 circulating
      inflammatory biomarkers was assayed by multiplex analysis. Partial least squares
      discriminant analysis (PLS-DA) was used to identify patterns of inflammatory
      mediators associated with gait speed categories. RESULTS: The optimal complexity
      of the PLS-DA model was found to be five latent variables. The proportion of
      correct classification was 88.9% for NW subjects (74.1% in cross-validation) and
      90.9% for SW individuals (81.8% in cross-validation). Discriminant biomarkers in
      the model were interleukin 8, myeloperoxidase, and tumor necrosis factor alpha
      (all higher in the SW group), and P-selectin, interferon gamma, and granulocyte
      macrophage colony-stimulating factor (all higher in the NW group). CONCLUSION:
      Distinct profiles of circulating inflammatory biomarkers characterize older
      subjects with different levels of physical performance. The dissection of these
      patterns may provide novel insights into the role played by inflammation in the
      disabling cascade and possible new targets for interventions.

PMID- 25593903
TI  - The grand challenge of nephrology.

PMID- 25593904
TI  - Having a Family Doctor is Associated with Some Better Patient-Reported Outcomes
      of Primary Care Consultations.
AB  - BACKGROUND: Hong Kong (HK) has pluralistic primary care that is provided by a
      variety of doctors. The aim of our study was to assess patient-reported outcomes
      of primary care consultations in HK and whether having a family doctor (FD) made
      any difference. METHODS: We interviewed by telephone 3148 subjects from 5174
      contacted households (response rate 60.8%) randomly selected from the general
      population of HK about the experience of their last primary care consultations in
      September 2007 and April 2008. We compared the patient-reported outcomes (PRO)
      and patient-centered process of care in those with a FD, those with other types
      of regular primary care doctors (ORD) and those without any regular primary care
      doctor (NRD). PRO included patient enablement, global improvement in health,
      overall satisfaction, and likelihood of recommending their doctors to family and
      friends. Patient-centered process of care indicators was explanations about the
      illness, and address of patient's concerns. RESULTS: One thousand one hundred
      fifty, 746, and 1157 reported to have FD, ORD, and NRD, respectively. Over 80% of
      those with FD consulted their usual primary care doctors in the last consultation
      compared with 27% of those with NRD. Compared with subjects having ORD or NRD,
      subjects with FD reported being more enabled after the consultation and were more
      likely to recommend their doctors to family and friends. Subjects with FD and ORD
      were more likely than those having NRD to report a global improvement in health
      and satisfaction. FD group was more likely than the other two groups to report
      receiving an explanation on the diagnosis, nature, and expected course of the
      illness, and having their concerns addressed. Patient enablement was associated
      with explanation of diagnosis, nature, and expected course of illness, and
      address of patient's concerns. CONCLUSION: People with a regular FD were more
      likely to feel being enabled and to experience patient-centered care in
      consultations.

PMID- 25593906
TI  - The Use of the Self-Standing Turning Transfer Device to Perform Bed-To-Chair
      Transfers Reduces Physical Stress among Caregivers of Older Patients in a Middle
      Income Developing Country.
AB  - Manual transfer of elderly patients remains commonplace in many developing
      countries because the use of lifting equipment, such as hoists, is often
      considered unaffordable luxuries. The aim of this study was, therefore, to
      evaluate the usage and potential benefits of a low-cost, mechanical turning
      transfer device among elderly patients and their caregivers on a geriatric ward
      in a developing country in South East Asia. Fifty-six inpatients, aged 66-92
      years, on a geriatric ward, and their caregivers were recruited. Participants
      were asked to transfer from bed-to-chair transfer with manual assistance, and the
      task was repeated using the Self-standing Turning Transfer Device (STurDi). The
      time taken to perform manual transfers and STurDi-assisted transfers was
      recorded. Physical strain was assessed using the perceived physical stress-rating
      tool for caregivers with and without the use of the device. User satisfaction was
      evaluated using the usefulness, satisfaction, and ease of use questionnaire.
      There was a significant reduction in transfer-time with manual transfers compared
      to STurDi-assisted transfers [mean (SD) = 48.39 (13.98) vs. 36.23 (10.96); p <=
      0.001]. The physical stress rating was significantly lower in STurDi-aided
      transfers compared to manual transfers, shoulder [median (interquartile range) =
      0 (1) vs. 4 (3); p = 0.001], upper back [0 (0) vs. 5 (4); p = 0.001], lower back
      [0 (1) vs. 5 (3), p = 0.001], whole body [1 (2) vs. 4 (3), p = 0.001], and knee
      [0 (1) vs. 1 (4), p = 0.001]. In addition, majority of patients and caregivers
      definitely or strongly agreed that the device was useful, saved time, and was
      easy to use. We have therefore demonstrated in a setting where manual handling
      was commonly performed that a low-cost mechanical transfer device reduced
      caregiver strain and was well received by older patients and caregivers. 

PMID- 25593907
TI  - Cyclosporine and Extracorporeal Photopheresis are Equipotent in Treating Severe
      Atopic Dermatitis: A Randomized Cross-Over Study Comparing Two Efficient
      Treatment Modalities.
AB  - BACKGROUND: Severe atopic dermatitis (AD) is a recurrent and debilitating disease
      often requiring systemic immunosuppressive treatment. The efficacy of
      cyclosporine A (CsA) is well proven but potential side effects are concerning.
      Several reports point at extracorporeal photopheresis (ECP) as an alternative
      treatment modality with few and mild side effects. However, no direct comparison
      between CsA and ECP in the treatment of AD has been performed so far. OBJECTIVES:
      To compare the efficacy of CsA (3 mg/kg/day) and ECP (administered two
      consecutive days twice a month) in a cohort of patients with severe AD. METHODS:
      A randomized cross-over study involving twenty patients with severe AD (SCORAD
      index 41-89) refractory to other treatments. The patients were allocated to a 4
      month course of either of the two treatment modalities. Individual relapse
      periods (2-8 weeks) were interspersed before cross-over to the other treatment
      modality. Treatment efficacy was evaluated by SCORAD, PRURITUS (VAS-index 0-10),
      "overall global assessment" and serological biomarkers; sIL-2Ralpha, sE-selectin,
      eosinophilocytes, basophilocytes, and sIgE. RESULTS: 15 patients completed
      treatment. Both treatments lead to a marked and significant decrease in SCORAD
      and pruritus index. The average reduction of the SCORAD and pruritus index,
      respectively was a little higher for ECP treatment compared to CsA treatment;
      however, the differences did not reach statistical significance. The "overall
      global assessment" was significantly better in patients who underwent ECP therapy
      as compared to CsA treatment. None of the biomarkers showed significant changes
      after either treatment when compared to the initial values. CONCLUSION: ECP
      administered on two consecutive days twice a month to patients with severe AD has
      similar potency as CsA administered daily in a moderate dose. ECP is a treatment
      alternative in patients with severe AD that do not tolerate or are refractory to
      conventional immunosuppressants.

PMID- 25593905
TI  - Detection of Bacteria Bearing Resistant Biofilm Forms, by Using the Universal and
      Specific PCR is Still Unhelpful in the Diagnosis of Periprosthetic Joint
      Infections.
AB  - Intraoperative conventional bacteriological cultures were compared with different
      polymerase chain reaction (PCR) methods in patients with total joint
      arthroplasties. The isolated bacteria were investigated for biofilm formation,
      and the biofilm forming strains, in their planktonic and biofilm forms, were
      further tested for their antimicrobial resistance against several clinically
      important antimicrobials. Forty four bone and joint samples were included and
      classified as infected or non-infected according to standard criteria for
      periprosthetic hip and knee infections. For the bacteriological diagnosis,
      conventional culture, two types of universal PCR and species specific PCR for
      three selected pathogens (Staphylococcus aureus, Staphylococcus epidermidis, and
      Pseudomonas aeruginosa) were applied. Biofilm formation determination was
      performed by the tissue culture plate method. Antimicrobial susceptibility of the
      planktonic bacteria was performed by the minimal inhibitory concentration
      determination and, of the biofilm forms, by the minimal inhibitory concentration
      for bacterial regrowth from the biofilm. Twenty samples were culture positive,
      with S. epidermidis, S. aureus, or P. aeruginosa. All PCR methods were very
      ineffective in detecting only one pathogen. All isolates were biofilm positive
      and their biofilm forms, were highly resistant. In this study, compared to PCR,
      culture remains the "gold standard." The biofilm formation by the causative
      bacteria and the concomitant manifold increased antimicrobial resistance may
      explain the clinical failure of treatment in some cases and should be considered
      in the future for therapeutic planning. 

PMID- 25593908
TI  - Helicobacter pylori: Emergence of a Superbug.

PMID- 25593910
TI  - Clinimetric testing in mexican elders: associations with age, gender, and place
      of residence.
AB  - AIM: To evaluate the ability of five clinimetric instruments to discriminate
      between subjects >60 years of age living at home versus those living in a
      residency. METHODS: Trained nutritionists applied five instruments
      (cognition/depression/functionality/nutrition/appetite) to 285 subjects with
      majorities of women (64%), aged <80 years (61%), and home residents (54%).
      RESULTS: Multivariable regression models were generated for each instrument using
      age, gender, and residency as independent variables. Age was associated with
      worsening scores in the five instruments whereas residency showed association in
      three instruments, and gender in two. Score-age regressions by place of residency
      showed differences suggesting that Mundet residents had increasingly worse scores
      with increasing age than home dwellers for cognition, depression, and nutrition.
      Also, living at home prevented the worsening of depression with increasing age.
      In contrast, functionality and appetite deteriorated at a similar rate for home
      and Mundet residents suggesting an inability of these two instruments to
      discriminate between settings. Score-age regressions by gender suggested that
      males have less cognitive problems at 60 and 80 years of age but not at 100
      years, and better appetite than women at all ages. CONCLUSION: Increasing age
      proved to be associated to worsening scores in the five instruments but only
      three were able to detect differences according to setting. An interesting
      observation was that living at home appeared to prevent the depression increase
      with increasing age seen in Mundet residents.

PMID- 25593909
TI  - Liver Diseases and Long Non-Coding RNAs: New Insight and Perspective.
AB  - The new landscape of human transcriptome along with the identification of
      numerous long non-coding RNAs (lncRNAs) has dramatically altered our approach to
      study diseases. It is now imperative to decipher the biological functions of
      these transcripts and how they impact on human cell and pathophysiology.
      Nonetheless, already at this very early stage of their study, the involvement of
      lncRNAs in cell transformation is emerging as a key aspect. Recently, researchers
      have started to explore the implications of lncRNAs alteration in hepatic
      pathophysiology. In this review, we will discuss in detail several examples of
      liver disease-relevant lncRNAs. Many lncRNAs have been shown to play a major role
      in hepatocellular carcinoma (HCC). For such type of tumor with an increasing
      incidence and a high mortality rate, it is crucial to identify new therapeutic
      targets and biomarkers to predict response to therapy. LncRNAs present as a
      promising new resource. One major challenge for the future would be to
      systematically address the lncRNAs expression among the different cellular
      components of the liver. To achieve this goal, a combination of clinically
      driven, genetically defined, morphologically classified, and molecular-based
      studies will have to be performed. In conclusion, lncRNAs will undoubtedly
      provide a rewarding field of study and most importantly a new resource to
      identify new disease associated biomarkers and molecular targets for therapy for
      liver diseases. 

PMID- 25593911
TI  - Primary health care and family medicine at the core of health care: challenges
      and priorities in how to further strengthen their potential.

PMID- 25593913
TI  - Dermatology: Where are We Coming from and Where are We Going to?

PMID- 25593912
TI  - Update on Molecular Pathology of Cutaneous Melanocytic Lesions: What is New in
      Diagnosis and Molecular Testing for Treatment?
AB  - In this article, we give an update on recent findings regarding molecular
      pathology in cutaneous melanocytic tumors. The focus lies on use of genetics in
      the diagnosis of distinct subtypes of spitzoid tumors that are often
      characterized by specific phenotypic-genotypic alterations that can frequently be
      recognized by adequate histological examination. Typical illustrating cases are
      given in order to increase recognition of these lesions in daily dermatopathology
      practice. New molecular findings in the pathogenesis of congenital melanocytic
      tumors and neurocutaneous melanosis are reviewed. In addition, use of mutation
      analysis in the differential diagnosis of melanoma metastasis is discussed.
      Finally, application of mutation analysis in targeted therapy in advanced
      melanoma with advantages of new techniques such as next generation sequencing is
      described. 

PMID- 25593914
TI  - Enhanced Mucosal Antibody Production and Protection against Respiratory
      Infections Following an Orally Administered Bacterial Extract.
AB  - Secondary bacterial infections following influenza infection are a pressing
      problem facing respiratory medicine. Although antibiotic treatment has been
      highly successful over recent decades, fatalities due to secondary bacterial
      infections remain one of the leading causes of death associated with influenza.
      We have assessed whether administration of a bacterial extract alone is
      sufficient to potentiate immune responses and protect against primary infection
      with influenza, and secondary infections with either Streptococcus pneumoniae or
      Klebsiella pneumoniae in mice. We show that oral administration with the
      bacterial extract, OM-85, leads to a maturation of dendritic cells and B-cells
      characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL.
      Improved immune responsiveness against influenza virus reduced the threshold of
      susceptibility to secondary bacterial infections, and thus protected the mice.
      The protection was associated with enhanced polyclonal B-cell activation and
      release of antibodies that were effective at neutralizing the virus. Taken
      together, these data show that oral administration of bacterial extracts provides
      sufficient mucosal immune stimulation to protect mice against a respiratory tract
      viral infection and associated sequelae. 

PMID- 25593915
TI  - Hemolytic uremic syndrome: toxins, vessels, and inflammation.
AB  - Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy of
      the glomerular microcirculation and other vascular beds. Its defining clinical
      phenotype is acute kidney injury (AKI), microangiopathic anemia, and
      thrombocytopenia. There are many etiologies of HUS including infection by Shiga
      toxin-producing bacterial strains, medications, viral infections, malignancy, and
      mutations of genes coding for proteins involved in the alternative pathway of
      complement. In the aggregate, although HUS is a rare disease, it is one of the
      most common causes of AKI in previously healthy children and accounts for a
      sizable number of pediatric and adult patients who progress to end stage kidney
      disease. There has been great progress over the past 20 years in understanding
      the pathophysiology of HUS and its related disorders. There has been intense
      focus on vascular injury in HUS as the major mechanism of disease and target for
      effective therapies for this acute illness. In all forms of HUS, there is
      evidence of both systemic and intra-glomerular inflammation and perturbations in
      the immune system. Renewed investigation into these aspects of HUS may prove
      helpful in developing new interventions that can attenuate glomerular and tubular
      injury and improve clinical outcomes in patients with HUS. 

PMID- 25593917
TI  - Pretargeted imaging and radioimmunotherapy of cancer using antibodies and
      bioorthogonal chemistry.
AB  - Selective delivery of radionuclides to tumors may be accomplished using a two
      step approach, in which in the first step the tumor is pretargeted with an
      unlabeled antibody construct and in the second step the tumor is targeted with a
      radiolabeled small molecule. This results in a more rapid clearance of the
      radioactivity from normal tissues due to the fast pharmacokinetics of the small
      molecule as compared to antibodies. In the last decade, several pretargeting
      approaches have been tested, which have shown improved tumor-to-background ratios
      and thus improved imaging and therapy as compared to directly labeled antibodies.
      In this review, we will discuss the strategies and applications in (pre-)clinical
      studies of pretargeting concepts based on the use of bispecific antibodies, which
      are capable of binding to both a target antigen and a radiolabeled peptide. So
      far, three generations of the bispecific antibody-based pretargeting approach
      have been studied. The first clinical studies have shown the feasibility and
      potential for these pretargeting systems to detect and treat tumor lesions.
      However, to fully integrate the pretargeting approach in clinic, further research
      should focus on the best regime and pretargeting protocol. Additionally, recent
      developments in the use of bioorthogonal chemistry for pretargeting of tumors
      suggest that this chemical pretargeting approach is an attractive alternative
      strategy for the detection and treatment of tumor lesions. 

PMID- 25593916
TI  - Gastrointestinal stromal tumor - an evolving concept.
AB  - Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors
      of the gastrointestinal tract. The discovery that these tumors, formerly thought
      of smooth muscle origin, are indeed better characterized by specific activating
      mutation in genes coding for the receptor tyrosine kinases (RTKs) CKIT and PDGFRA
      and that these mutations are strongly predictive for the response to targeted
      therapy with RTK inhibitors has made GISTs the typical example of the integration
      of basic molecular knowledge in the daily clinical activity. The information on
      the mutational status of these tumors is essential to predict (and subsequently
      to plan) the therapy. As resistant cases are frequently wild type, other possible
      oncogenic events, defining other "entities," have been discovered (e.g., succinil
      dehydrogenase mutation/dysregulation, insuline growth factor expression, and
      mutations in the RAS-RAF-MAPK pathway). The classification of disease must
      nowadays rely on the integration of the clinico-morphological characteristics
      with the molecular data. 

PMID- 25593919
TI  - Yellow Nail Syndrome and Nail Lichen Planus may be Induced by a Common Culprit.
      Focus on Dental Restorative Substances.
AB  - Different clinical appearances such as Yellow nail syndrome and Lichen planus or
      lichenoid reactions can originate from close or identical etiologies. They may
      result from dental restorative materials or metal allergy. Interestingly, the
      nail sometimes returns to its normal condition, months after the withdrawal of
      the offending agents. 

PMID- 25593918
TI  - A Small Molecule beta2 Integrin Agonist Improves Chronic Kidney Allograft
      Survival by Reducing Leukocyte Recruitment and Accompanying Vasculopathy.
AB  - Kidney allograft rejection is associated with infiltration of inflammatory CD11b+
      leukocytes. A CD11b agonist leukadherin-1 (LA1) increases leukocyte adhesion,
      preventing their transmigration and tissue recruitment in vivo. Here, we test the
      extent to which LA1-mediated activation of CD11b/CD18 enhances kidney allograft
      survival in a mouse model of fully MHC-mismatched orthotopic kidney
      transplantation, where C57BL/6J (H-2(b)) recipients received kidney allografts
      from Balb/c mice (H-2(d)). Isograft control recipients received a kidney from a
      littermate. Control isograft and allograft recipients were treated daily with
      cyclosporine (CsA) for 2 weeks, while the test group received CsA therapy and
      daily LA1 injections during week 1 and alternate days during weeks 2-8. LA1
      treatment reduced interstitial leukocyte infiltration in the allograft, reduced
      neointimal hyperplasia and glomerular damage, and prolonged graft survival from
      48.5% (CsA only) to 100% (CsA and LA1) on day 60. Serum creatinine levels showed
      significantly improved kidney function in LA1-treated mice compared to CsA
      treated allograft controls [0.52 +/- 0.18 mg/dL vs 0.24 +/- 0.07 mg/dL (n = 5),
      respectively]. Furthermore, combination therapy reduced macrophage infiltration
      and increased the frequency of FoxP3 + Tregs in the allograft. These findings
      indicate a crucial role for CD11b/CD18 in the control of leukocyte migration to
      the transplanted kidney and identify integrin agonist LA1 as a novel potential
      therapeutic agent for kidney transplantation. 

PMID- 25593920
TI  - STAT3 Single Nucleotide Polymorphism rs4796793 SNP Does Not Correlate with
      Response to Adjuvant IFNalpha Therapy in Stage III Melanoma Patients.
AB  - Interferon alpha (IFNalpha) is approved for adjuvant treatment of stage III
      melanoma in Europe and the US. Its clinical efficacy, however, is restricted to a
      subpopulation of patients while side effects occur in most of treated patients.
      Thus, the identification of predictive biomarkers would be highly beneficial to
      improve the benefit to risk ratio. In this regard, STAT3 is important for
      signaling of the IFNalpha receptor. Moreover, the STAT3 single-nucleotide
      polymorphism (SNP) rs4796793 has recently been reported to be associated with
      IFNalpha sensitivity in metastatic renal cell carcinoma. To translate this notion
      to melanoma, we scrutinized the impact of rs4796793 functionally and clinically
      in this cancer. Interestingly, melanoma cells carrying the minor allele of
      rs4796793 were the most sensitive to IFNalpha in vitro. However, we did not
      detect a correlation between SNP genotype and STAT3 mRNA expression for either
      melanoma cells or for peripheral blood lymphocytes. Next, we analyzed the impact
      of rs4796793 on the clinical outcome of 259 stage III melanoma patients of which
      one-third had received adjuvant IFNalpha treatment. These analyses did not reveal
      a significant association between the STAT3 rs4796793 SNP and patients'
      progression free or overall survival when IFNalpha treated and untreated patients
      were compared. In conclusion, STAT3 rs4796793 SNP is no predictive marker for the
      efficacy of adjuvant IFNalpha treatment in melanoma patients. 

PMID- 25593921
TI  - Placental amniotic epithelial cells and their therapeutic potential in liver
      diseases.
AB  - As a unique source of stem cells, there is a growing interest in amniotic
      epithelial (AE) cells. Placenta is readily available; in fact, it is often
      discarded following delivery. As such, it is without the ethical concerns of
      embryonic stem cells. Further advantages to AE include that AE cells do not
      demonstrate tumorigenicity upon transplantation, and are gifted with
      immunomodulatory and anti-inflammatory properties. Thus, AE cells have
      exceptional features for use as cell-based therapies for liver disease. 

PMID- 25593923
TI  - A Different Approach of Dizziness in Older Patients: Away from the Diagnostic
      Dance between Patient and Physician.
AB  - Although the etiology of dizziness in older patients differs significantly from
      that of younger patients, most guidelines on dizziness advocate the same
      diagnosis-oriented approach for all patients regardless of their age. However,
      this diagnosis-oriented approach may be insufficient for older patients
      presenting with dizziness in general practice, because (1) general practitioners
      are often not able to identify an underlying cause of dizziness, (2) general
      practitioners regularly identify causes of dizziness that cannot be treated, and
      (3) general practitioners may identify causes of dizziness for which treatment is
      available but not desirable. In this article, the authors present a simultaneous
      diagnosis- and prognosis-oriented approach for older dizzy patients. This
      approach may enable general practitioners to improve their care for a voluminous
      group of impaired older patients, even if a diagnosis is not available (yet). 

PMID- 25593922
TI  - Gastrointestinal symptoms in morbid obesity.
AB  - BACKGROUND: Several reports have shown an increased prevalence of
      gastrointestinal (GI) symptoms in obese subjects in community-based studies. To
      better understand the role of the GI tract in obesity, and because there are
      limited clinic-based studies, we documented the prevalence of upper and lower GI
      symptoms in morbidly obese individuals in a clinic setting. OBJECTIVE: The aim of
      our study was to compare the prevalence of GI symptoms in morbidly obese
      individuals in a weight management clinic with non-obese individuals with similar
      comorbidities as morbidly obese individuals in an Internal Medicine clinic.
      METHODS: Class II and III obese patients BMI >35 kg/m(2) (N = 114) and 182 non
      obese patients (BMI <25 kg/m(2)) completed the GI symptoms survey between August
      2011 and April 2012 were included in this study. The survey included 24 items
      pertaining to upper and lower GI symptoms. The participants rated the frequency
      of symptoms as absent (never, rarely) or present (occasionally, frequently). The
      symptoms were clustered into five categories: oral symptoms, dysphagia,
      gastroesophageal reflux, abdominal pain, and bowel habits. Responses to each
      symptom cluster were compared between obese group and normal weight groups using
      logistic regression. RESULTS: Of the 24 items, 18 had a higher frequency in the
      obese group (p < 0.005 for each). After adjusting for age and gender, the obese
      patients were more likely to have upper GI symptoms: any oral symptom (OR = 2.3,
      p = 0.0013), dysphagia (OR 2.9, p = 0.0006), and any gastroesophageal reflux (OR
      3.8, p < 0.0001). Similarly, the obese patients were more likely to have lower GI
      symptoms: any abdominal pain (OR = 1.7, p = 0.042) and altered bowel habits (OR =
      2.8, p < 0.0001). CONCLUSION: These observations suggest a statistically
      significant increase in frequency of both upper and lower GI symptoms in morbidly
      obese patients when compared to non-obese subjects.

PMID- 25593924
TI  - Characteristics of adults with down syndrome: prevalence of age-related
      conditions.
AB  - INTRODUCTION: In the last decades, life expectancy of persons with Down syndrome
      (DS) has dramatically increased and it is estimated that they will be living as
      long as the general population within a generation. Despite being included among
      the progeroid syndromes, because of the presence of features typically observed
      in older adults, DS is still regarded as a disease of pediatric interest. Because
      limited knowledge is available on the clinical characteristics of adults with DS,
      this study aimed to assess clinical and non-clinical features of this population
      and to describe similarities to the geriatric population. METHODS: In this study,
      we described 60 adults with DS evaluated at the Day Hospital of the Geriatric
      Department of the Policlinico A. Gemelli, Universita Cattolica del Sacro Cuore in
      Rome. Individuals were assessed through a standardized protocol. RESULTS: The
      mean age of study participants was 38 years (range, 18-58 years) and 42 (70.0%)
      were women. Geriatric conditions were highly prevalent: severe cognitive
      impairment was diagnosed in 39 (65.0%) participants, behavioral symptoms were
      present in 25 (41.7%), and functional impairment in 23 (38.3%). Six (10.0%)
      participants lived in institutions and 11 (18.3%) were diagnosed as obese. The
      mean number of drugs used was 2.4; use of psychotropic drugs was highly
      prevalent. The most common chronic diseases were thyroid problems (44, 73.3%),
      followed by mood disorders (19, 31.7%), osteoporosis (18, 30.0%), and cardiac
      problems (10, 16.7%). Geriatric conditions and chronic diseases were more
      prevalent among participants aged >=40 years. CONCLUSION: Several similarities
      between older adults and adults with DS were observed. Comorbidities, geriatric
      conditions, cognitive and functional deficits, and social problems are highly
      prevalent in both populations, contributing to the high complexity of these
      patients' assessment and treatment.

PMID- 25593926
TI  - Prognostic Value and Clinical Impact of (18)FDG-PET in the Management of Children
      with Burkitt Lymphoma after Induction Chemotherapy.
AB  - OBJECTIVE: Burkitt lymphoma (BL) is a rare and aggressive form of B-cell lymphoma
      that is curable using intensive chemotherapy. Obtaining a complete response (CR)
      at the end of induction chemotherapy is a major prognostic factor. This study
      retrospectively evaluates the potential impact of (18)FDG-PET in the management
      of children with BL after induction chemotherapy, and the prognostic performance
      of the Deauville criteria. METHODS: Nineteen children with BL treated according
      to the French LMB2001 protocol between 2005 and 2012 were included. (18)FDG-PET
      and conventional imaging (CI) were performed after induction chemotherapy to
      confirm CR. (18)FDG-PET was interpreted according to Deauville criteria with
      follow-up and/or histology as the gold standard. RESULTS: (18)FDG-PET was
      negative in 15 cases, in agreement with CI in 9/15 cases. The six discordant
      cases confirmed to be negative by histology, were considered as true negative for
      (18)FDG-PET. Negative predictive value (NPV) of CI and (18)FDG-PET were 73 and
      93%, respectively. The 5-year progression-free survival (PFS) was significantly
      higher in patients with negative (18)FDG-PET than those with positive (18)FDG-PET
      (p = 0.011). CONCLUSION: (18)FDG-PET interpreted using Deauville criteria can
      help confirm CR at the end of induction chemotherapy, with a prognostic impact on
      5-year PFS. Its high NPV could limit the use of residual mass biopsy. Given the
      small size of our population, these results need to be confirmed by future
      prospective studies on a larger population.

PMID- 25593925
TI  - Atypical hemolytic uremic syndrome post-kidney transplantation: two case reports
      and review of the literature.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by
      over-activation and dysregulation of the alternative complement pathway. Its
      estimated prevalence is 1-2 per million. The disease is characterized by
      thrombotic microangiopathy, which causes anemia, thrombocytopenia, and acute
      renal failure. aHUS has more severe course compared to typical (infection
      induced) HUS and is frequently characterized by relapses that leads to end stage
      renal disease. For a long time, kidney transplantation for these patients was
      contraindicated because of high rate of recurrence and subsequent renal graft
      loss. The post-kidney transplantation recurrence rate largely depends on the
      pathogenetic mechanisms involved. However, over the past several years,
      advancements in the understanding and therapeutics of aHUS have allowed
      successful kidney transplantation in these patients. Eculizumab, which is a
      complement C5 antibody that inhibits complement factor 5a and subsequent
      formation of the membrane-attack complex, has been used in prevention and
      treatment of post-transplant aHUS recurrence. In this paper, we present two new
      cases of aHUS patients who underwent successful kidney transplantation in our
      center with the use of prophylactic and maintenance eculizumab therapy that have
      not been published before. The purpose of reporting these two cases is to
      emphasize the importance of using eculizumab as a prophylactic therapy to prevent
      aHUS recurrence post-transplant in high-risk patients. We will also review the
      current understanding of the genetics of aHUS, the pathogenesis of its recurrence
      after kidney transplantation, and strategies for prevention and treatment of post
      transplant aHUS recurrence. 

PMID- 25593927
TI  - Endoplasmic reticulum stress in endometrial cancer.
AB  - Endometrial cancer (EC) is a common gynecologic malignancy often diagnosed at
      early stage. In spite of a huge advance in our understanding of EC biology,
      therapeutic modalities do not have significantly changed over the past 40 years.
      A restricted number of genes have been reported to be mutated in EC, mediating
      cell proliferation and invasiveness. However, besides these alterations, few
      other groups and ourselves recently identified the activation of the unfolded
      protein response (UPR) and GRP78 increase following endoplasmic reticulum (ER)
      stress as mechanisms favoring growth and invasion of EC cells. Here, a concise
      update on currently available data in the field is presented, analyzing the
      crosstalk between the UPR and the main signaling pathways regulating EC cell
      proliferation and survival. It is evident that this is a rapidly expanding and
      promising issue. However, more data are very likely to yield a better
      understanding on the mechanisms through which EC cells can survive the low oxygen
      and glucose tumor microenvironment. In this perspective, the UPR and,
      particularly, GRP78 might constitute a novel target for the treatment of EC in
      combination with traditional adjuvant therapy. 

PMID- 25593928
TI  - Perturbations in the urinary exosome in transplant rejection.
AB  - BACKGROUND: Urine exosomes are small vesicles exocytosed into the urine by all
      renal epithelial cell types under normal physiologic and disease states. Urine
      exosomal proteins may mirror disease specific proteome perturbations in kidney
      injury. Analysis methodologies for the exosomal fraction of the urinary proteome
      were developed for comparing the urinary exosomal fraction versus unfractionated
      proteome for biomarker discovery. METHODS: Urine exosomes were isolated by
      centrifugal filtration of urine samples collected from kidney transplant patients
      with and without acute rejection (AR), which were biopsy matched. The proteomes
      of unfractionated whole urine (Uw) and urine exosomes (Ue) underwent mass
      spectroscopy-based quantitative proteomics analysis. The proteome data were
      analyzed for significant differential protein abundances in AR. RESULTS: A total
      of 1018 proteins were identified in Uw and 349 proteins in Ue. Two hundred
      seventy-nine overlapped between the two urinary compartments and 70 proteins were
      unique to the Ue compartment. Of 349 exosomal proteins identified from transplant
      patients, 220 had not been previously identified in the normal Ue fraction.
      Eleven Ue proteins, functionally involved in an inflammatory and stress response,
      were more abundant in urine samples from patients with AR, three of which are
      exclusive to the Ue fraction. Ue AR-specific biomarkers (1) were also detected in
      Uw, but since they were observed at significantly lower abundances in Uw, they
      were not significant for AR in Uw. CONCLUSION: A rapid urinary exosome isolation
      method and quantitative measurement of enriched Ue proteins was applied.
      Perturbed proteins in the exosomal compartment of urine collected from kidney
      transplant patients were specific to inflammatory responses, and were not
      observed in the Ue fraction from normal healthy subjects. Ue-specific protein
      alterations in renal disease provide potential mechanistic insights and offer a
      unique panel of sensitive biomarkers for monitoring AR.

PMID- 25593929
TI  - Reassessing the Reassessment of suPAR in Glomerular Disease.

PMID- 25593930
TI  - Perspective: the challenge of clinical decision-making for drug treatment in
      older people. The role of multidimensional assessment and prognosis.
AB  - A complex decision path with a careful evaluation of the risk-benefit ratio is
      mandatory for drug treatment in advanced age. Enrollment biases in randomized
      clinical trials (RCTs) cause an under-representation of older individuals. In
      high-risk frail older subjects, the lack of RCTs makes clinical decision-making
      particularly difficult. Frail individuals are markedly susceptible to adverse
      drug reactions, and frailty may result in reduced treatment efficacy. Life
      expectancy should be included in clinical decision-making paths to better assess
      the benefits and risks of different drug treatments in advanced age. We performed
      a scoping review of principal hospital- and community-based prognostic indices in
      older age. Mortality prognostic tools could help clinical decision-making in
      diagnostics and therapeutics, tailoring appropriate intervention for older
      patients. The effectiveness of drug treatments may be significantly different in
      older patients with different risk of mortality. Clinicians need to consider the
      prognostic information obtained through well-validated, accurate, and calibrated
      predictive tools to identify those patients who may benefit from drug treatments
      given with the aim of increasing survival. 

PMID- 25593931
TI  - Laparoscopic treatment of placenta percreta retention in a cesarean scar: a case
      report.
AB  - Placenta percreta retention within the scar of a previous cesarean section is
      rare. We report here one of these cases treated successfully by laparoscopy, with
      uterine repair. Different therapeutic options are described. 

PMID- 25593933
TI  - Robotically assisted gynecologic surgery: 2-year experience in the French foch
      hospital.
AB  - Robotically assisted laparoscopic surgery has seen rapid expansion over the past
      few years and it constantly evolves with a progressive enlargement of its range
      of indications. In the present paper we would like to share our 2-year experience
      regarding the use of robotics in various laparoscopic procedures, including
      hysterectomy, myomectomy, adnexal surgery, and sacrocolpopexy. 

PMID- 25593934
TI  - The grand challenge - managing end-staged joint osteoarthritis.

PMID- 25593932
TI  - Pig-islet xenotransplantation: recent progress and current perspectives.
AB  - Islet xenotransplantation is one prospective treatment to bridge the gap between
      available human cells and needs of patients with diabetes. Pig represents an
      ideal candidate for obtaining such available cells. However, potential clinical
      application of pig islet still faces obstacles including inadequate yield of high
      quality functional islets and xenorejection of the transplants. Adequate amounts
      of available islets can be obtained by selection of a suitable pathogen-free
      source herd and the development of isolation and purification method. Several
      studies demonstrated the feasibility of successful preclinical pig-islet
      xenotransplantation and provided insights and possible mechanisms of xenogeneic
      immune recognition and rejection. Particularly promising is the achievement of
      long-term insulin independence in diabetic models by means of distinct islet
      products and novel immunotherapeutic strategies. Nonetheless, further efforts are
      needed to obtain much more safety and efficacy data to translate these findings
      into clinic. 

PMID- 25593935
TI  - Impact of future remnant liver volume on post-hepatectomy regeneration in non
      cirrhotic livers.
AB  - OBJECTIVE: The purpose of the study is to detect if some parameters can be
      considered as predictors of liver regeneration in two different patient
      populations composed of in living donors for adult to adult living donor liver
      transplant and patients with hepatic malignancies within a single institution.
      SUMMARY BACKGROUND DATA: Preoperative multi-detector computed tomography
      volumetry is an essential tool to assess the volume of the remnant liver.
      METHODS: A retrospective analysis from an ongoing clinical study on 100 liver
      resections, between 2004 and 2010. Seventy patients were right lobe living donors
      for liver transplantation and 30 patients were resected for treatment of tumors.
      Pre-surgical factors such as age, weight, height, body mass index (BMI), original
      liver volume, future remnant liver volume (FRLV), spleen volume, liver function
      tests, creatinine, platelet count, steatosis, portal vein embolization, and
      number of resected segments were analyzed to evidence potential markers for liver
      regeneration. RESULTS: Follow-up period did not influence the amount of liver
      regenerated: the linear regression evidenced that there is no correlation between
      percentage of liver regeneration and time of follow-up (p = 0.88). The pre
      surgical variables that resulted markers of liver regeneration include higher
      preoperative values of BMI (p = 0.01), bilirubin (p = 0.04), glucose (p = 0.05),
      and gamma-glutamyl transpeptidase (p = 0.014); the most important association was
      revealed regarding the lower FRLV (p < 0.0001) and percentage of liver
      regeneration. The stepwise regression revealed a strong impact of FRLV (p <
      0.0001) on the other predictor variables. CONCLUSION: Liver regeneration follows
      similar pathway in living donor and in patients resected for cancer. Small FRLV
      tends to regenerate more and faster, confirming that a larger resections may lead
      to a greater promotion of liver regeneration in patients with optimal conditions
      in terms of body habitus, preoperative liver function tests, and glucose level.

PMID- 25593937
TI  - The need for registries in the early scientific evaluation of surgical
      innovations.

PMID- 25593936
TI  - Grand challenge: on the way to scarless visceral surgery.

PMID- 25593938
TI  - Endometriosis and ovarian cancer risk: a systematic review of epidemiological
      studies.
AB  - BACKGROUND: A possible etiological association between endometriosis and ovarian
      cancer has been repeatedly reported in the literature. OBJECTIVE: Our aim was to
      evaluate published epidemiological data on this issue. REVIEW METHODS: We
      conducted an extensive search of the literature in MEDLINE, of articles ever
      published until February 2014, using the key-words "endometriosis" and "ovarian"
      and one of the following terms in the title: "cancer" or "malignancy" or
      "malignant" or "tumor" or "neoplasia" or "neoplasm" or "transformation."
      Retrieved papers were checked for further relevant publications. RESULTS:
      Overall, our search yielded 1 prospective cohort study, 10 retrospective cohort,
      and 5 case-control studies. A meta-analysis of these studies was not considered
      to be appropriate, due to differences in data reporting, study design, and
      adjustment for confounding factors. LIMITATIONS: The main limitation of studies
      found, with one exception, was the lack of operative confirmation of
      endometriosis. CONCLUSION: An association of endometriosis with clear-cell and
      endometrioid ovarian cancer was a consistent finding in most studies. On the
      other hand, existing epidemiological evidence linking endometriosis with ovarian
      cancer is insufficient to change current clinical practice. Prospective cohort
      studies, with prior laparoscopic confirmation, localization, and staging of
      endometriosis are needed, in order to further clarify this issue.

PMID- 25593939
TI  - Robotic vs. Standard Laparoscopic Technique - What is Better?
AB  - INTRODUCTION: Laparoscopic surgery is subject to certain limitations that can be
      a problem when performing complex minimally invasive operations. Robotic surgery
      was developed precisely to overcome such technical limitations. The question
      therefore arises whether robotic surgery leads to significantly better results
      compared with standard laparoscopic surgery. METHODS: Based on comparative
      systematic reviews and meta-analyses, this paper examines whether the robotic
      technique when used for abdominal and visceral surgery procedures confers
      advantages on the patient compared with the standard laparoscopic technique.
      RESULTS: Even for demanding visceral surgery procedures, the perioperative
      complication rate for robotic surgery is not higher than for open or laparoscopic
      surgical procedures. In cancer cases, the oncological accuracy of robotic
      resection for gastric, pancreatic, and rectal resection is seen to be adequate.
      Only the operating time is generally longer than for standard laparoscopic and
      open procedures. But, on the other hand, in some procedures blood loss is less,
      conversion rates are lower and hospital stay shorter. CONCLUSION: To evaluate the
      future role of the robotic technique for visceral surgery, high-quality
      prospective randomized trials are urgently needed.

PMID- 25593941
TI  - Modified plug repair with limited sphincter sparing fistulectomy in the treatment
      of complex anal fistulas.
AB  - PURPOSE: New technical approaches involving biologically derived products have
      been used to treat complex anal fistulas in order to avoid the risk of fecal
      incontinence. The least invasive methods involve filling out the fistula tract
      with fibrin glue or introduction of an anal fistula plug into the fistula canal
      following thorough curettage. A review shows that the new techniques involving
      biologically derived products do not confer any significant advantages.
      Therefore, the question inevitably arises as to whether the combination of a
      partial or limited fistulectomy, i.e., of the extrasphincteric portion of the
      fistula, and preservation of the sphincter muscle by repairing the section of the
      complex anal fistula running through the sphincter muscle and filling it with a
      fistula plug produces better results. METHODS: A modified plug technique was
      used, in which the extrasphincteric portion of the complex anal fistula was
      removed by means of a limited fistulectomy and the remaining section of the
      fistula in the sphincter muscle was repaired using the fistula plug with fixing
      button. RESULTS: Of the 52 patients with a complex anal fistula, who had
      undergone surgery using a modified plug repair with limited fistulectomy of the
      extrasphincteric part of the fistula and use of the fistula plug with fixing
      button, there are from 40 patients (follow-up rate: 77%) some kind of follow-up
      informations, after a mean of 19.32 +/- 6.9 months. Thirty-two were men and eight
      were women, with a mean age of 52.97 +/- 12.22 years. Surgery was conducted to
      treat 36 transsphincteric, 1 intersphincteric, and 3 rectovaginal fistulas. In 36
      of 40 patients (90%), the complex anal fistulas or rectovaginal fistulas were
      completely healed without any sign of recurrence. None of these patients
      complained about continence problems. CONCLUSION: A modification of the plug
      repair of complex anal fistulas with limited fistulectomy of the extrasphincteric
      part of the fistula and use of the plug with fixing button seems to increase the
      healing rate in comparison to the standard plug technique.

PMID- 25593940
TI  - Endometriosis: a new cellular and molecular genetic approach for understanding
      the pathogenesis and evolutivity.
AB  - Endometriosis is a benign disease with high prevalence in women of reproductive
      age estimated between 10 and 15% and is associated with considerable morbidity.
      Its etiology and pathogenesis are controversial but it is believed to involve
      multiple genetic, environmental, immunological, angiogenic, and endocrine
      processes. Altered expressions of growth factors, cytokines, adhesion molecules,
      matrix metalloproteinases, and enzymes for estrogen synthesis and metabolism have
      been frequently observed in this condition. The possibility of genetic basis of
      endometriosis is demonstrated in studies of familial disease, in which the
      incidence of endometriosis is higher for first-degree relatives of probands as
      compared to controls. This review describes mainly the cellular, cytochemical,
      cytogenetic, and molecular genetic features of endometriotic lesions and cultured
      endometriotic cells. In attempts to identify candidate gene (s) involved in the
      pathogenesis of endometriosis, a tissue-based approaches including conventional
      cytogenetics (RHG-banding), loss of heterozygosity (LOH), and comparative genomic
      hybridization (CGH) were employed. In addition to the karyotypic anomalies,
      consistent chromosome instability was confirmed by CGH and fluorescence in situ
      hybridization (FISH). The nature and significance of the molecular genetic
      aberrations in relation to the locations and function of oncogenes and tumor
      suppressor genes will be discussed. At last, a possible pathogenic role of
      embryonic duct remnants was observed in seven female fetal reproductive tract in
      endometriosis and may induce a discussion about the beginning of ovarian tumors
      and malignant proliferations. 

PMID- 25593942
TI  - The Value of Automated Follicle Volume Measurements in IVF/ICSI.
AB  - BACKGROUND/AIMS: The objective of this literature study is to investigate the
      place of recent software technology sonography-based automated volume count
      (SonoAVC) for the automatic measurement of follicular volumes in IVF/ICSI. Its
      advantages and disadvantages and potential future developments are evaluated.
      METHODS: A total of 74 articles were read via a PubMed literature study. The
      literature study included 53 articles, 32 of which for the systematic review.
      RESULTS: The SonoAVC software shows excellent accuracy. Comparing the technology
      with the "golden standard" two-dimensional (2D) manual follicle measurements,
      SonoAVC leads to a significantly lower intra- and inter-observer variability.
      However, there is no significant difference in clinical outcome (pregnancy rate).
      We noted a significant advantage in the time gained, both for doctor and patient.
      By storing the images, the technology offers the possibility of including a
      quality control and continuous training and further standardization of follicular
      monitoring can be expected. Ovarian reserve testing by measuring the antral
      follicle count with SonoAVC is highly reliable. CONCLUSION: This overview of
      previously published literature shows how SonoAVC offers advantages for clinical
      practice, without losing any accuracy or reliability. Doctors should be motivated
      to the general use of follicular volumes instead of follicular diameters.

PMID- 25593943
TI  - Gynecology and Obstetrics has Entered Modern Times: Perspectives and Challenges.

PMID- 25593944
TI  - Tailored approach in inguinal hernia repair - decision tree based on the
      guidelines.
AB  - The endoscopic procedures TEP and TAPP and the open techniques Lichtenstein, Plug
      and Patch, and PHS currently represent the gold standard in inguinal hernia
      repair recommended in the guidelines of the European Hernia Society, the
      International Endohernia Society, and the European Association of Endoscopic
      Surgery. Eighty-two percent of experienced hernia surgeons use the "tailored
      approach," the differentiated use of the several inguinal hernia repair
      techniques depending on the findings of the patient, trying to minimize the
      risks. The following differential therapeutic situations must be distinguished in
      inguinal hernia repair: unilateral in men, unilateral in women, bilateral,
      scrotal, after previous pelvic and lower abdominal surgery, no general anesthesia
      possible, recurrence, and emergency surgery. Evidence-based guidelines and
      consensus conferences of experts give recommendations for the best approach in
      the individual situation of a patient. This review tries to summarize the
      recommendations of the various guidelines and to transfer them into a practical
      decision tree for the daily work of surgeons performing inguinal hernia repair. 

PMID- 25593946
TI  - Successful treatment of colorectal anastomotic stricture by using
      sphincterotomes.
AB  - Colorectal or colocolic anastomotic stricture is a common complication after
      colorectal surgery. Traditionally, endoscopic balloon dilation technique was used
      for those patients with symptomatic stricture. The use of electroincision (radial
      incisions of the scar) along with pneumatic balloon dilation was reported with
      good result in literature. We present a novel method for relieving colorectal
      anastomotic stricture by using sphincterotomes, which is indicated for use in the
      cannulation of the biliary ducts and the transendoscopic sphincterotomy of the
      papilla of Vater and the sphincter of Oddi. The use of sphincterotomes in upper
      GI tract anastomotic stricture was reported before, but the experience in
      managing lower GI tract was pending. Based on our preliminary report,
      sphincterotomes can be an effective and safe treatment option for colorectal
      anastomotic stricture. 

PMID- 25593947
TI  - Circular Versus Linear Versus Hand-Sewn Gastrojejunostomy in Roux-en-Y-Gastric
      Bypass Influence on Weight Loss and Amelioration of Comorbidities: Data Analysis
      from a Quality Assurance Study of the Surgical Treatment of Obesity in Germany.
AB  - BACKGROUND: Since January 1 2005, the outcomes of bariatric surgeries have been
      recorded in Germany. All data are registered prospectively in cooperation with
      the Institute of Quality Assurance in Surgery at Otto-von-Guericke University
      Magdeburg. METHODS: Data are collected in an online data bank. Data collection
      began in 2005 for the results of Roux-en-Y-Gastric Bypass (RYGB). In addition to
      primary bariatric operations, data regarding the complications and the
      amelioration of comorbidities have been analyzed. Participation in the quality
      assurance study is required for all certified centers in Germany. RESULTS: Roux
      en-Y Gastric Bypass is the most popular bariatric operation in Germany. There
      were 5115 operations performed from 2005 to 2010. A circular anastomosis was
      performed in 1587 patients, and a linear anastomosis was performed in 2734
      patients. In 783 patients, the hand-sewn technique was used. The leakage rate for
      the linear technique is 1.6%, and the leakage rate is 1.2% for circular
      anastomosis, and 1.4% for hand-sewn technique. CONCLUSION: Roux-en-Y-Gastric
      Bypass is a popular procedure in Germany. The complication rate has decreased
      since 2005. The amelioration of comorbidities is not influenced by the
      anastomosis technique. Additional data are necessary to evaluate the long-term
      effect of linear versus hand-sewn and versus circular-stapled gastrojejunal
      anastomosis regarding pouch dilatation, small bowel dilatation, and consecutive
      weight loss.

PMID- 25593945
TI  - Recent advances in liver resection for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The
      association of HCC with chronic liver disease (CLD) is well known and making
      treatment complex and challenging. The treatment of HCC must take into
      consideration, the severity of CLD, the stage of HCC, and the clinical condition
      of the patient. Liver resection (LR) is one of the most efficient treatments for
      patients with HCC. Better liver function assessment, increased understanding of
      segmental liver anatomy using more accurate imaging studies, and surgical
      technical progress are the important factors that have led to reduced mortality,
      with an expected 5 year survival of 38-61% depending on the stage of the disease.
      However, the procedure is applicable to <30% of all HCC patients, and 80% of the
      patients after LR recurred within 5 years. There are recent advances and
      prospects in LR for HCC in several aspects. Three-dimensional computed tomography
      imaging assisted preoperative surgical planning facilitates unconventional types
      of LR. Emerging evidences of laparoscopic hepatectomy and prospects for the use
      of newly developing chemotherapies as a combined therapy may lead to expanding
      indication of LR. LR and liver transplantation could be associated rather than
      considered separately with the current concepts of "bridging LR" and "salvage
      transplantation." 

PMID- 25593948
TI  - Endometriosis and infertility: how and when to treat?
AB  - Endometriosis is defined as the presence of endometrial-like tissue (glands or
      stroma) outside the uterus, which induces a chronic inflammatory reaction.
      Although endometriosis impairs fertility, it does not usually completely prevent
      conception. The question of evidence based-medicine guidelines in endometriosis
      associated infertility is weak in many situations. Therefore, we will highlight
      in this issue where the challenges are. 

PMID- 25593949
TI  - Analysis of donor motivations in living donor liver transplantation.
AB  - OBJECTIVES: The introduction of the living donor liver transplantation (LDLT) in
      Egypt as in elsewhere, has raised important psychological conflicts and ethical
      questions. The objective of this study was to get better understanding of the
      potential donors' motives toward LDLT. METHODS: This study was conducted on
      consecutive 193 living-liver donors who underwent partial hepatectomy as donors
      for LDLT during the period between April 2003 and January 2013, at the National
      Liver Institute Menoufeyia University, Egypt. Potential donors were thoroughly
      evaluated preoperatively through a screening questionnaire and interviews as
      regard their demographic data, relationship to the potential recipient, and
      motives toward proceeding to surgery. They were assured that the information
      shared between them and the transplant center is confidential. RESULTS: The
      donors' mean age was 25.53 +/- 6.39 years with a range of 18-45 years. Males
      represented 64.7% and females were 35.3%. The most common donors (32.1%, n = 62)
      were sons and daughters to their parents (sons: n = 43, daughters: n = 19) while
      parents to their offsprings represent 15% (mothers: n = 21, fathers: n = 8).
      Brothers and sisters represent 16.5% (brothers: n = 22, sisters: n = 10). Nephews
      and nieces giving their uncles or aunts were 14%. The number of wives donating to
      their husbands was 11 (5.7%). Interestingly, there was no single husband who
      donated his wife. Among the remaining donors, there were 11 cousins and 1 uncle.
      Unrelated donors were 20 (10.4%). Several factors seemed to contribute to
      motivation for donation: the seriousness of the potential recipient condition,
      the relationship and personal history of the donor to the potential recipient,
      the religious beliefs, the trust in the health care system, and family dynamics
      and obligations. CONCLUSION: Absolute absence of coercion on the living-liver
      donor's motives may not be realistic because of the serious condition of the
      potential recipient. It is mandatory that the donor is truly willing to donate.

PMID- 25593950
TI  - What is a Certified Hernia Center? The Example of the German Hernia Society and
      German Society of General and Visceral Surgery.
AB  - To date, the scientific definition "hernia center" does not exist and this term
      is being used by hospitals and private institutions as a marketing instrument.
      Hernia surgery has become increasingly more complex over the past 25 years.
      Differentiated use of the various techniques in hernia surgery has been adopted
      as a "tailored approach" program and requires intensive engagement with, and
      extensive experience of, the entire field of hernia surgery. Therefore, there is
      a need for hernia centers. A basic requirement for a credible certification
      process for hernia centers involves definition of requirements and its
      verification by hernia societies and/or non-profit organizations that are
      interested in assuring the best possible quality of hernia surgery. At present,
      there are two processes for certification of hernia centers by hernia societies
      or non-profit organizations. 

PMID- 25593951
TI  - Orthopedic oncology - "the challenges ahead".

PMID- 25593952
TI  - Mid-Gestational Enlargement of Fetal Thalami in Women Exposed to Methadone during
      Pregnancy.
AB  - Methadone maintenance therapy is the standard of care in many countries for
      opioid-dependent women who become pregnant. Despite recent evidence showing
      significant neurodevelopmental changes in children and adults exposed to both
      licit and illicit substances in utero, data on the effects of opioids in
      particular remains scarce. The purpose of this study was to examine the effects
      of opiate use, in particular methadone, on various fetal cortical and biometric
      growth parameters in utero using ultrasound measurements done at 18-22 weeks
      gestation. Head circumference (HC), bi-parietal diameter, lateral ventricle
      diameter, transcerebellar diameter, thalamic diameter, cisterna magna diameter,
      and femur length were compared between fetuses born to methadone-maintained
      mothers and non-substance using controls. A significantly larger thalamic
      diameter (0.05 cm, p = 0.01) was observed in the opiate-exposed group. Thalamic
      diameter/HC ratio was also significantly raised (0.03 mm, p = 0.01). We
      hypothesize here that the increase in thalamic diameter in opiate-exposed fetuses
      could potentially be explained by regional differences in opioid and serotonin
      receptor densities, an alteration in monoamine neurotransmitter systems, and an
      enhancement of the normal growth increase that occurs in the thalamus during mid
      gestation. 

PMID- 25593954
TI  - Vascular surgery, quo vadis?

PMID- 25593953
TI  - The impact of liver transplantation after surgical treatment of hepatocellular
      carcinoma.
AB  - BACKGROUND: The impact of liver transplantation (LTx) after surgical treatment
      for hepatocellular carcinoma (HCC) remains undefined. The aim of the current
      study was to assess the impact of LTx and of selection criteria for LTx on the
      survival of patients who underwent surgery for HCC. METHODS: Between 2004 and
      2009, 119 patients underwent surgical treatment for HCC. Cirrhosis was present in
      85 patients. Of all patients, 77 fulfilled the Milan criteria, 88 the UCSF and 87
      the up-to-7 criteria. Finally, 35 patients received an LTx, of whom 31 met the
      Milan, 33 the UCSF, and 33 the up-to-7 criteria. The relation between LTx and
      survival was evaluated using a Cox regression model with LTx as a time-dependent
      factor. RESULTS: Median [95% confidence interval (CI)] disease-free survival
      (DFS) and overall survival (OS) of the entire patient population was 9.4 (7-12.2)
      and 49.1 (37.7-64) months, respectively. The 1, 3, and 5-year DFS vs. OS rates
      were 36, 3, and 0% vs. 84.7, 61.7, and 39.6%, respectively. Patients fulfilling
      the Milan criteria had a significantly better OS and DFS than those who had
      tumors beyond the Milan criteria (p < 0.047). No significant differences were
      observed in terms of OS between patients within vs. beyond the UCSF or up-to-7
      criteria (p > 0.130). In multivariable analysis, cirrhotic patients who received
      an LTx had a better OS, with a hazard ratio equal to 0.25 (95% CI: 0.08-0.74; p <
      0.01). LTx after surgery had a beneficial impact on both DFS and OS of patients
      in all the three selection criteria models of LTx (p < 0.031). CONCLUSION: LTx
      after primary surgery seems to offer the best long-term survival for patients
      suffering from HCC in cirrhosis as well as for them who fulfill the Milan, UCSF,
      and up-to-7 criteria.

PMID- 25593955
TI  - Placental site trophoblastic tumor: a case report and review of the literature.
AB  - Placental site trophoblastic tumor is rare. They represent a rare form of
      gestational trophoblastic disease. They occur mainly in women who have a history
      of miscarriage, termination of pregnancy, or even a normal or pathological
      ongoing pregnancy. The clinical course is unpredictable. This malignancy has
      different characteristics from other gestational trophoblastic tumors. Following
      a clinical case that we encountered and treated, we conducted a literary research
      and review, focusing primarily on prognostic factors and treatment. 

PMID- 25593957
TI  - Progress in heart surgery: let the magic continue.

PMID- 25593956
TI  - Minimal incision scar-less open umbilical hernia repair in adults - technical
      aspects and short-term results.
AB  - BACKGROUND: There is no gold standard technique for umbilical hernia (UH) repair.
      Conventional open UH repair often produces an undesirable scar. Laparoscopic UH
      repair requires multiple incisions beyond the umbilicus, specialized equipments,
      and expensive tissue separating mesh. We describe our technique of open UH repair
      utilizing a small incision. The technique was derived from our experience with
      single incision laparoscopy. We report the technical details and short-term
      results. METHODS: This is a retrospective analysis of the first 20 patients, who
      underwent minimal incision scar-less open UH repair, from June 2011 to February
      2014. A single intra-umbilical curved incision was used to gain access to the
      hernia sac. Primary suture repair was performed for defects up to 2 cm. Larger
      defects were repaired using an onlay mesh. In patients with a BMI of 30 kg/m(2)
      or greater, onlay mesh hernioplasty was performed irrespective of the defect
      size. RESULTS: A total of 20 patients, 12 males and 8 females underwent the
      procedure. Mean age was 50 (range 29-82) years. Mean BMI was 26.27 (range 20.0
      33.1) kg/m(2). Average size of the incision was 1.96 range (1.5-2.5) cm. Mesh
      hernioplasty was done in nine patients. Eleven patients underwent primary suture
      repair alone. There were no postoperative complications associated with this
      technique. Average postoperative length of hospital stay was 3.9 (range 2-10)
      days. Mean follow-up was 29.94 months (2 weeks to 2.78 years). On follow-up there
      was no externally visible scar in any of the patients. There were no recurrences
      on final follow-up. CONCLUSION: This technique provides a similar cosmetic effect
      as obtained from single port laparoscopy. It is easy to perform, safe, offers
      good cosmesis, does not require incisions beyond the umbilicus, and cost
      effective, with encouraging results on short-term follow-up. Further research is
      needed to assess the true potential of the technique and the long-term results.

PMID- 25593958
TI  - Laparoscopic management of interstitial pregnancy and fertility outcomes after
      ipsilateral salpingectomy - three case reports.
AB  - BACKGROUND: Interstitial pregnancy after ipsilateral salpingectomy is a rare
      event with potentially serious consequences. Optimal management strategy remains
      uncertain and debated. In addition, fertility sparing is determinant of the
      treatment choice. CASES: Here, we report three cases of interstitial pregnancy
      occurring after homolateral salpingectomy. We expose the therapeutic option held
      in all three situations, which associated laparoscopic procedure followed by
      intramuscular methotrexate injection with successful outcome for all patients. We
      also report the fertility outcome for the first patient, discussing the timing
      and mode of delivery. Cesarean section at term was performed for this patient.
      CONCLUSION: In these three situations, we obtained a successful result using a
      minimally invasive surgical approach combined with systemic methotrexate
      injection. Cesarean section at term for subsequent intrauterine pregnancy seems
      to be the safest delivery strategy, although no clear data exist in literature.

PMID- 25593959
TI  - The Immediate Post-Operative Radiograph is an Unreliable Measure of Coronal Plane
      Alignment in Total Knee Replacement.
AB  - BACKGROUND: Restoration of a neutral mechanical axis is a primary goal of total
      knee replacement (TKR). A mechanical axis within 3 degrees  of neutral has been
      correlated with improved implant longevity, function, and patient satisfaction.
      We hypothesize that the immediate post-operative radiograph is an unreliable
      method of measuring alignment following TKR surgery. METHODS: Seventy-five
      consecutive patients had supine X-rays performed on day two post-operatively
      followed by standing long-leg radiographs (LLRs) 6 weeks post-operatively.
      Correlation was sought between the mechanical axis measured on the LLR and
      surrogate markers of alignment on the post-operative X-ray including component
      alignment and an estimation of anatomical alignment using the available length of
      femoral and tibial shafts. Inter- and intra-observer reliabilities were assessed.
      RESULTS: The mean mechanical axis on the LLR was 180.5 (SD 3.0, range 175.1
      187.1). Mean offset between anatomical axis and mechanical axis was 6.4 degrees .
      The mean anatomical axis measured on the short-leg X-ray was 174.9 (SD 2.4, range
      169.5-181.3). Mechanical axis on the LLR was compared to the anatomical axis
      measured on the short-leg radiograph (SLR) + 6 degrees  with an interclass
      correlation coefficient of 0.588 (p < 0.001). The level of disagreement between
      the short- and long-leg X-rays was assessed using the Bland-Altman method and
      demonstrated clinically important discrepancies of 5 or more degrees in 9% of
      cases. Inter- and intra-observer agreements were high on all measures (p <
      0.001). CONCLUSION: The long-leg weight bearing X-ray is an essential tool to
      accurately assess coronal plane alignment post TKR. While the immediate post
      operative X-ray taken supine provides useful information to the surgeon on any
      immediate complications, our results indicate that it cannot be relied upon to
      determine correct restoration of the mechanical axis.

PMID- 25593961
TI  - A sheep model for cancellous bone healing.
AB  - Appropriate well-characterized bone defect animal models remain essential for
      preclinical research. This pilot study demonstrates a relevant animal model for
      cancellous bone defect healing. Three different defect diameters (8, 11, 14 mm)
      of fixed depth (25 mm) were compared in both skeletally immature (18-month-old)
      and aged sheep (5-year-old). In each animal, four defects were surgically created
      and placed in the cancellous bone of the medial distal femoral and proximal
      tibial epiphyses bilaterally. Animals were euthanized at 4 weeks post-operatively
      to assess early healing and any biological response. Defect sites were graded
      radiographically, and new bone formation quantified using MUCT and
      histomorphometry. Fibrous tissue was found within the central region in most of
      the defects with woven bone normally forming near the periphery of the defect.
      Bone volume fraction [bone volume (BV)/TV] significantly decreased with an
      increasing defect diameter. Actual BV, however, increased with defect diameter.
      Bone ingrowth was lower for all defect diameters in the aged group. This pilot
      study proposes that the surgical creation of 11 mm diameter defects in the
      proximal tibial and distal femoral epiphyses of aged sheep is a suitable large
      animal model to study early healing of cancellous bone defects. The refined model
      allows for the placement of four separate bone defects per animal and encourages
      a reduction in animal numbers required for preclinical research. 

PMID- 25593960
TI  - Current concepts in the management of necrotizing fasciitis.
AB  - Necrotizing fasciitis (NF) is a severe, rare, potentially lethal soft tissue
      infection that develops in the scrotum and perineum, the abdominal wall, or the
      extremities. The infection progresses rapidly, and septic shock may ensue; hence,
      the mortality rate is high (median mortality 32.2%). Prognosis becomes poorer in
      the presence of co-morbidities, such as diabetes mellitus, immunosuppression,
      chronic alcohol disease, chronic renal failure, and liver cirrhosis. NF is
      classified into four types, depending on microbiological findings. Most cases are
      polymicrobial, classed as type I. The clinical status of the patient varies from
      erythema, swelling, and tenderness in the early stage to skin ischemia with
      blisters and bullae in the advanced stage of infection. In its fulminant form,
      the patient is critically ill with signs and symptoms of severe septic shock and
      multiple organ dysfunction. The clinical condition is the most important clue for
      diagnosis. However, in equivocal cases, the diagnosis and severity of the
      infection can be secured with laboratory-based scoring systems, such as the
      laboratory risk indicator for necrotizing fasciitis score or Fournier's gangrene
      severity index score, especially in regard to Fournier's gangrene. Computed
      tomography or ultrasonography can be helpful, but definitive diagnosis is
      attained by exploratory surgery at the infected sites. Management of the
      infection begins with broad-spectrum antibiotics, but early and aggressive
      drainage and meticulous debridement constitute the mainstay of treatment.
      Postoperative management of the surgical wound is also important for the
      patient's survival, along with proper nutrition. The vacuum-assisted closure
      system has proved to be helpful in wound management, with its combined benefits
      of continuous cleansing of the wound and the formation of granulation tissue. 

PMID- 25593963
TI  - The application of wearable technology in surgery: ensuring the positive impact
      of the wearable revolution on surgical patients.
AB  - Wearable technology has become an important trend in consumer electronics in the
      past year. The miniaturization and mass production of myriad sensors have made
      possible the integration of sensors and output devices in wearable platforms.
      Despite the consumer focus of the wearable revolution some surgical applications
      are being developed. These fall into augmentative, assistive, and assessment
      functions and primarily layer onto current surgical workflows. Some challenges to
      the adoption of wearable technologies are discussed and a conceptual framework
      for understanding the potential of wearable technology to revolutionize surgical
      practice are presented. 

PMID- 25593962
TI  - Biology of infantile hemangioma.
AB  - Infantile hemangioma (IH), the most common tumor of infancy, is characterized by
      an initial proliferation during infancy followed by spontaneous involution over
      the next 5-10 years, often leaving a fibro-fatty residuum. IH is traditionally
      considered a tumor of the microvasculature. However, recent data show the
      critical role of stem cells in the biology of IH with emerging evidence
      suggesting an embryonic developmental anomaly due to aberrant proliferation and
      differentiation of a hemogenic endothelium with a neural crest phenotype that
      possesses the capacity for endothelial, hematopoietic, mesenchymal, and neuronal
      differentiation. Current evidence suggests a putative placental chorionic
      mesenchymal core cell embolic origin of IH during the first trimester. This
      review outlines the emerging role of stem cells and their interplay with the
      cytokine niche that promotes a post-natal environment conducive for
      vasculogenesis involving VEGFR-2 and its ligand VEGF-A and the IGF-2 ligand in
      promoting cellular proliferation, and the TRAIL-OPG anti-apoptotic pathway in
      preventing cellular apoptosis in IH. The discovery of the role of the renin
      angiotensin system in the biology of IH provides a plausible explanation for the
      programed biologic behavior and the beta-blocker-induced accelerated involution
      of this enigmatic condition. This crucially involves the vasoactive peptide,
      angiotensin II, that promotes cellular proliferation in IH predominantly via its
      action on the ATIIR2 isoform. The role of the RAS in the biology of IH is further
      supported by the effect of captopril, an ACE inhibitor, in inducing accelerated
      involution of IH. The discovery of the critical role of RAS in IH represents a
      novel and fascinating paradigm shift in the understanding of human development,
      IH, and other tumors in general. 

PMID- 25593964
TI  - Applying evidence-based medicine principles to hip fracture management.
AB  - Bone has the capacity to regenerate and not scar after injury - sometimes leaving
      behind no evidence at all of a prior fracture. As surgeons capable of
      facilitating such healing, it becomes our responsibility to help choose a
      treatment that minimizes functional deficits and residual symptoms. And in the
      case of the geriatric hip fracture, we have seen the accumulation of a vast
      amount of evidence to help guide us. The best method we currently have for
      selecting treatment plans is by the practice of evidence-based medicine.
      According to the now accepted hierarchy, the best is called Level I evidence
      (e.g., well performed randomized controlled trials) - but this evidence is best
      only if it is available and appropriate. Lower forms of accepted evidence include
      cohort studies, case control studies, case series, and case reports, and last,
      expert opinion - all of which can be potentially instructive. The hallmark of
      evidence-based treatment is not so much the reliance on evidence in general, but
      to use the best available evidence relative to the particular patient, the
      clinical setting and surgeon experience. Correctly applied, varying forms of
      evidence each have a role in aiding surgeons offer appropriate care for their
      patients - to help them best fix the fracture. 

PMID- 25593965
TI  - Platelet-rich plasma guided injections: clinical application in peripheral
      neuropathies.
AB  - Platelet-rich plasma (PRP) is defined as an autologous concentrated preparation
      of platelets and their associated growth factors in a small volume of plasma. The
      presence of these growth factors has stimulated the scientific community to
      search about possible benefits of the use of PRP in tissue regeneration. Provided
      that previously in vitro and animal research demonstrated that PRP could probably
      play an important role in the treatment of neural tissue disorders, we aimed to
      review the current literature, regarding the clinical studies that have been
      conducted to confirm this hypothesis. More specifically, we have reviewed the
      literature concerning the clinical application of PRP in peripheral neuropathies
      and investigated if there is strong evidence to establish the use of PRP in
      clinical practice as a therapeutic option. In contrast with animal studies, we
      have been able to identify only few clinical data concerning the use of PRP in
      peripheral neuropathies. We found five trials matched to our research that yields
      positive and promising results for the future for the application of PRP for the
      therapy of disorders of the peripheral nervous system. It is obvious that this
      interesting field of research gives to the scientists the ability to expand it
      extensively, in terms of both quality and quantity. 

PMID- 25593966
TI  - Plastic surgery for the oncological patient.
AB  - The therapy of oncological patients has seen tremendous progress in the last
      decades. For most entities, it has been possible to improve the survival as well
      as the quality of life of the affected patients. To supply optimal cancer care, a
      multidisciplinary approach is vital. Together with oncologists, radiotherapists
      and other physicians, plastic surgeons can contribute to providing such care in
      all stages of treatment. From biopsies to the resection of advanced tumors, the
      coverage of the resulting defects and even palliative care, plastic surgery
      techniques can help to improve survival and quality of life as well as mitigate
      negative effects of radiation or the problems arising from exulcerating tumors in
      a palliative setting. This article aims to present the mentioned possibilities by
      illustrating selected cases and reviewing the literature. Especially in
      oncological patients, restoring their quality of life with the highest patient
      safety possible is of utmost importance. 

PMID- 25593967
TI  - A new removable uterine compression by a brace suture in the management of severe
      postpartum hemorrhage.
AB  - Postpartum hemorrhage (PPH) is a life-threatening complication of delivery. It is
      the leading cause of maternal mortality. During the last 15 years, several total
      uterine compressive sutures were described in literature. They have proven their
      effectiveness and safety in the management of severe PPH as an alternative to
      hysterectomy. We present in this paper a new technique of uterine compressive
      sutures based on removable uterine brace compressive sutures with compression of
      the uterus against the pubis. This technique may be more effective by using two
      mechanisms of uterine bleeding control and also may prevent uterine synechia by
      respecting the uterine cavity and the removal of the suture 1 or 2 days later. We
      also present the results of a 15 patients' series using this new suture. 

PMID- 25593968
TI  - BMP4 and LGL1 are Down Regulated in an Ovine Model of Congenital Diaphragmatic
      Hernia.
AB  - BACKGROUND/PURPOSE: The molecular pathophysiology of lung hypoplasia in
      congenital diaphragmatic hernia (CDH) remains poorly understood. The Wnt
      signaling pathway and downstream targets, such as bone morphogenetic proteins
      (BMP) 4 and other factors such as late gestation lung protein 1 (LGL1), are
      essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent
      lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced
      LGL1 expression. The aim of the current study was to examine the molecular
      pathophysiology associated with a surgically induced CDH in an ovine model.
      METHODS: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was
      created in seven experimental animals. Lungs were harvested at 136 days (term =
      145 days). Lung weight (LW) and mean terminal bronchiole density (MTBD) were
      measured to determine the degree of pulmonary hypoplasia. Quantitative real time
      PCR was undertaken to analyze Wnt2, Wnt7b, BMP4, and LGL1 mRNA expression.
      RESULTS: Total LW was decreased while MTBD was increased in the CDH group (p <
      0.05), confirming pulmonary hypoplasia. BMP4 and LGL1 mRNA was significantly
      reduced in CDH lungs (p < 0.05). Wnt2 mRNA was decreased, although not
      significantly (p < 0.06). CONCLUSION: For the first time, down regulation of BMP4
      and LGL1 are reported in an ovine CDH model. In contrast to other animal models,
      these changes are persistent to near term. These findings suggest that mechanical
      compression from herniated viscera may play a more important role in causing
      pulmonary hypoplasia in CDH, rather than a primary defect in lung organogenesis.

PMID- 25593969
TI  - Assessment of Pain and Quality of Life in Lichtenstein Hernia Repair Using a New
      Monofilament PTFE Mesh: Comparison of Suture vs. Fibrin-Sealant Mesh Fixation.
AB  - BACKGROUND: Inguinal hernia repair is one of the most common operations in
      general surgery. The Lichtenstein tension-free operation has become the gold
      standard in open inguinal hernia repair. Despite the low recurrence rates, pain
      and discomfort remain a problem for a large number of patients. The aim of this
      study was to compare suture fixation vs. fibrin sealing by using a new
      monofilament PTFE mesh, i.e., the Infinit((r)) mesh by W. L. Gore & Associates.
      METHODS: This study was designed as a controlled prospective single-center two
      cohort study. A total of 38 patients were enrolled and operated in Lichtenstein
      technique either standard suture mesh fixation or fibrin-sealant mesh fixation
      were used as described in the TIMELI trial. Primary outcome parameters were
      postoperative complications with the new mesh (i.e., seroma, infection), pain,
      and quality of life evaluated by the VAS and the SF-36 questionnaire. Secondary
      outcome was recurrence assessed by ultrasound and physical examination. Follow-up
      time was 1 year. RESULTS: Significantly, less postoperative pain was reported in
      the fibrin-sealant group compared to the suture group at 6 weeks (P = 0.035), 6
      months (P = 0.023), and 1 year (P = 0.011) postoperatively. Additionally, trends
      toward a higher postoperative quality of life, a faster surgical procedure, and a
      shorter hospital stay were seen in the fibrin-sealant group. CONCLUSION: Fibrin
      sealant mesh fixation in Lichtenstein hernioplasty effectively reduces acute and
      chronic postoperative pain. Monofilament, macro-porous, knitted PTFE meshes seem
      to be a practicable alternative to commonly used polypropylene meshes in open
      inguinal hernia repair.

PMID- 25593970
TI  - Supplemental Cardioplegia Immediately before Graft Implantation may Improve Early
      Post-Transplantation Outcome.
AB  - BACKGROUND: Preservation of cardiac grafts for transplantation is not
      standardized and most centers use a single administration of crystalloid solution
      at the time of harvesting. We investigated possible benefits of an additional
      dose of cardioplegia dispensed immediately before implantation. METHODS:
      Consecutive adult cardiac transplantations (2005-2012) were reviewed. Hearts were
      harvested following a standard protocol (Celsior 2L, 4-8 degrees C). In 2008, 100
      ml crystalloid cardioplegic solution was added and administered immediately
      before implantation. Univariate and logistic regression analyses were used to
      investigate risk factors for post-operative graft failure and mid-term outcome.
      RESULTS: A total of 81 patients, 44 standard ("Cardio(-)") vs. 37 with additional
      cardioplegia ("Cardio(+)") were analyzed. Recipients and donors were comparable
      in both groups. Cardio(+) patients demonstrated a reduced need for defibrillation
      (24 vs. 48%, p = 0.03), post-operative ratio of CK-MB/CK (10.1 +/- 3.9 vs. 13.3
      +/- 4.2%, p = 0.001), intubation time (2.0 +/- 1.6 vs. 7.2 +/- 11.5 days, p =
      0.05), and ICU stay (3.9 +/- 2.1 vs. 8.5 +/- 7.8 days, p = 0.001). Actuarial
      survival was reduced when graft ischemic time was >180 min in Cardio(-) but not
      in Cardio(+) patients (p = 0.033). Organ ischemic time >180 min (OR: 5.48, CI:
      1.08-27.75), donor female gender (OR: 5.84, CI: 1.13-33.01), and recipient/donor
      age >60 (OR: 6.33, CI: 0.86-46.75), but not the additional cardioplegia or the
      observation period appeared independent predictors of post-operative acute graft
      failure. CONCLUSION: An additional dose of cardioplegia administered immediately
      before implantation may be a simple way to improve early and late outcome of
      cardiac transplantation, especially in situations of prolonged graft ischemia. A
      large, ideally multicentric, randomized study is desirable to verify this
      preliminary observation.

PMID- 25593971
TI  - In Search of Better Spermatogonial Preservation by Supplementation of
      Cryopreserved Human Immature Testicular Tissue Xenografts with N-acetylcysteine
      and Testosterone.
AB  - Controlled slow-freezing is the procedure currently applied for immature
      testicular tissue (ITT) cryobanking in clinical practice. Vitrification has been
      proposed as a promising alternative, with a view to better preserve the
      spermatogonial stem cells for future fertility restoration by autografting in
      young boys suffering from cancer. It appears that besides the potential influence
      of the cryopreservation technique used, the transplantation procedure itself has
      a significant impact on spermatogonial loss observed in ITT xenografts. Eighteen
      ITT pieces issued from 6 patients aged 2-15 years were used. Fragments of fresh
      tissue (serving as ungrafted controls), frozen-thawed tissue, frozen-thawed
      tissue supplemented with N-acetylcysteine (NAC), and frozen-thawed tissue
      supplemented with testosterone xenografted to nude mice for 5 days were compared.
      Upon graft removal, histological and immunohistochemical analyses were performed
      to evaluate spermatogonia, intratubular proliferation, and intrinsic and
      extrinsic apoptosis. A significant decrease in the integrity of intact
      seminiferous tubules was found in all three grafted groups. Spermatogonia were
      observed by immunohistochemistry in all grafted groups, with recovery rates of
      67, 63, and 53%, respectively, for slow-frozen tissue, slow-frozen tissue
      supplemented with NAC, and slow-frozen tissue supplemented with testosterone.
      Apoptosis evidenced by active caspase-3 and terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling was similar in all grafts. The study is limited
      by the low availability of ITT samples of human origin, and no clear impact of
      graft supplementation was found. The mouse xenotransplantation model needs to be
      refined to investigate human spermatogenesis in human ITT grafts. 

PMID- 25593972
TI  - Elevated Infant Mortality Rate among Dutch Oral Cleft Cases: A Retrospective
      Analysis from 1997 to 2011.
AB  - OBJECTIVES: First, to determine the infant mortality rate (IMR) for Dutch
      patients with isolated oral clefts (OC) as well as for patients with clefts seen
      in association with other malformations. Second, to conduct a similar analysis
      per cleft type: cleft lip with or without cleft palate (CP), CP (including Robin
      sequence). Third, to examine the underlying causes of death. MATERIAL AND
      METHODS: A retrospective review of the charts of patients with OC born in the
      period 1997-2011 and treated in three regional cleft centers in the Netherlands.
      RESULTS: One thousand five hundred thirty patients with OC were born during the
      study period and treated in the cleft centers. The overall IMR for all clefts was
      2.09%, significantly higher than the general Dutch IMR of 0.45%. In a subanalysis
      per cleft type, the IMRs were 1.22, 1.38, 2.45, and 3.62% for cleft lip, cleft
      lip with CP, CP, and Robin sequence, respectively. The mortality rates for
      isolated OC did not differ significantly from the general Dutch rate. Causes of
      death were congenital malformations of the heart in 40.6%, airway/lungs in 15.6%,
      nervous system in 15.6%, infectious disease in 12.5%, and other or unknown in
      15.6%. CONCLUSION: The elevated IMR observed in Dutch patients with OC is almost
      exclusively caused by associated congenital malformations. After diagnosis of an
      oral cleft an in-depth medical examination and a consult by the pediatrician and
      clinical geneticist is imperative to instigate the appropriate medical
      management.

PMID- 25593973
TI  - Retroperitoneal tumors in the pelvis: a diagnostic challenge in gynecology.
AB  - Retroperitoneal tumors can pose a diagnostic and therapeutic challenge to
      gynecologists because of their rarity, late presentation, and complex anatomical
      location in the retroperitoneum. This article reviews the diagnosis and
      management of retroperitoneal tumors in the pelvis, and highlights the potential
      pitfalls that may be faced by gynecologists. 

PMID- 25593974
TI  - Immunohistochemistry - microarray analysis of patients with peritoneal metastases
      of appendiceal or colorectal origin.
AB  - BACKGROUND: The value of immunohistochemistry (IHC)-microarray analysis of
      pathological specimens in the management of patients is controversial, although
      preliminary data suggest potential benefit. We describe the characteristics of
      patients undergoing a commercially available IHC-microarray method in patients
      with peritoneal metastases (PM) and the feasibility of this technique in this
      population. METHODS: We retrospectively analyzed consecutive patients with
      pathologically confirmed PM from appendiceal or colorectal primary who underwent
      Caris Molecular Intelligence(TM) testing. IHC, microarray, FISH, and mutational
      analysis were included and stratified by Peritoneal Carcinomatosis Index (PCI)
      score, histology, and treatment characteristics. Statistical analysis was
      performed using non-parametric tests. RESULTS: Our study included 5 patients with
      appendiceal and 11 with colorectal PM. The median age of patients was 51 (IQR 39
      65) years, with 11 (68%) female. The median PCI score of the patients was 17 (IQR
      10-25). Hyperthermic intra-peritoneal chemoperfusion was performed in 4 (80%)
      patients with appendiceal primary tumors and 4 (36%) with colorectal primary.
      KRAS mutations were encountered in 40% of appendiceal vs. 30% colorectal tumors,
      while BRAF mutations were seen in 40% of colorectal PM and none of the patients
      with appendiceal PM (p = 0.06). IHC biomarker expression was not significantly
      different between the two primaries. Sufficient tumor for microarray analysis was
      found in 44% (n = 7) patients, which was not associated with previous use of
      chemotherapy (p > 0.20 for 5-FU/LV, Irinotecan and Oxaliplatin). CONCLUSION: In a
      small sample of patients with PM, the feasibility and results of IHC-microarray
      staining based on a commercially available test is reported. The apparent high
      incidence of the BRAF mutation in patients with PM may potentially offer
      opportunities for novel therapeutics and suggest that IHC-microarray is a method
      that can be used in this population.

PMID- 25593976
TI  - Surveillance of the Remaining Nodules after Resection of the Dominant Lung
      Adenocarcinoma is an Appropriate Follow-Up Strategy.
AB  - INTRODUCTION: Adenocarcinomas, commonly present as a dominant lesion (DL) with
      additional nodules in the ipsilateral or contralateral lung. We sought to
      determine the fate and management of the secondary nodules and to assess the risk
      of these nodules using the Lung CT Screening Reporting and Data System (Lung
      RADS) criteria and the National Comprehensive Cancer Network (NCCN) Guidelines to
      determine if surveillance is an appropriate strategy. METHODS: We retrospectively
      evaluated patients with lepidic growth pattern adenocarcinoma and secondary
      nodules from 2000 to 2013. Risk assessment of the additional lesions was
      completed with a simplified model of Lung-RADS and NCCN-Guidelines. RESULTS:
      Eighty-seven patients underwent resection of 87 DLs (Group 1) concurrently with
      60 additional pulmonary nodules (Group 2), while 157 non-DLs were radiologically
      surveyed over a median follow-up time of 3.2 years (Group 3). Malignancy was
      found in 29/60 (48%) nodules in Group 2. Whereas, only 9/157 (6%) of the lesions
      in Group 3 enlarged, 4 of which (2.5% of total) were found to be malignant, and
      then treated, while the remaining nodules continued surveillance. After applying
      the Lung-RADS and NCCN simplified models, nodules in Group 2 were at higher risk
      for lung cancer than those in Group 3. CONCLUSION: In patients with lepidic
      growth pattern adenocarcinoma associated with multiple secondary nodules,
      surveillance of the remaining nodules, after resection of the DL, is a reasonable
      strategy since these nodules exhibited a slow rate of growth and minimal
      malignancy. In contrast, nodules resected from the ipsilateral lung at the time
      of the DL, harbor malignancy in 48%. Risk assessment models may provide a useful
      and standardized tool for clinical assessment of pulmonary nodules.

PMID- 25593975
TI  - Somatic stem cells and their dysfunction in endometriosis.
AB  - Emerging evidence indicates that somatic stem cells (SSCs) of different types
      prominently contribute to endometrium-associated disorders such as endometriosis.
      We reviewed the pertinent studies available on PubMed, published in English
      language until December 2014 and focused on the involvement of SSCs in the
      pathogenesis of this common gynecological disease. A concise summary of the data
      obtained from in vitro experiments, animal models, and human tissue analyses
      provides insights into the SSC dysregulation in endometriotic lesions. In
      addition, a set of research results is presented supporting that SSC-targeting,
      in combination with hormonal therapy, may result in improved control of the
      disease, while a more in-depth characterization of endometriosis SSCs may
      contribute to the development of early-disease diagnostic tests with increased
      sensitivity and specificity. Key message: Seemingly essential for the
      establishment and progression of endometriotic lesions, dysregulated SSCs, and
      associated molecular alterations hold a promise as potential endometriosis
      markers and therapeutic targets. 

PMID- 25593977
TI  - Effects of Physician Communication and Family Hardiness on Patient Medication
      Regimen Beliefs and Adherence.
AB  - This study aims to develop a model that describes how physician communication and
      family hardiness affect medication regimen beliefs and adherence for patients on
      regimens to control diabetes and hyperlipidemia (high cholesterol). Study
      participants (n=1356) completed self-report questionnaires on health beliefs.
      Pharmacy refill records from a health plan in the United States provided data on
      their medication adherence. Structural equation modeling was used to model
      variable relationships. A mediation analysis demonstrated that physician
      communication behaviors had a significant impact on the patients' behavioral
      intention to adhere to their regimen and medication adherence when they were
      mediated by the patient's medication taking health beliefs related to perceived
      benefit of the regimen, impact of side effects, and cost of regimen. Conversely,
      family hardiness had no effect on medication-taking behaviors. To improve patient
      medication-taking behaviors, physician communication behaviors should be
      targeted. The study suggests the physician's initial regimen discussion is
      important to both regimen initiation and long-term adherence, and should
      emphasize the regimen's benefits and how to avoid common side effects. Also,
      establishing a follow-up physician-patient relationship can enhance regimen
      adherence and reduce the likelihood that a patient will stop taking the
      medication due to cost concerns. The research supports the important role the
      physician plays in health behavior maintenance. Future research should study the
      effect physicians have on other recurring health behaviors.

PMID- 25593978
TI  - Diffuse correlation spectroscopy for measurement of cerebral blood flow: future
      prospects.
AB  - Diffuse correlation spectroscopy (DCS) is an emerging optical modality used to
      measure cortical cerebral blood flow. This outlook presents a brief overview of
      the technology, summarizing the advantages and limitations of the method, and
      describing its recent applications to animal, adult, and infant cohorts. At last,
      the paper highlights future applications where DCS may play a pivotal role
      individualizing patient management and enhancing our understanding of
      neurovascular coupling, activation, and brain development.

PMID- 25593979
TI  - MET nucleotide variations and amplification in advanced ovarian cancer:
      characteristics and outcomes with c-Met inhibitors.
AB  - PURPOSE: MET alterations including amplifications and nucleotide variations have
      been associated with resistance to therapy and aggressive clinical behavior.
      EXPERIMENTAL DESIGN: The medical records of patients presenting to the University
      of Texas MD Anderson Cancer Center Phase I Clinic with relapsed or metastatic
      ovarian cancers and known MET nucleotide variation or amplification status were
      reviewed retrospectively (n=178). Categorical and continuous clinical and
      molecular characteristics were compared using Fisher's exact and Wilcoxon rank
      sum tests, respectively. Univariate and multivariate survival were assessed via
      Kaplan-Meier and Cox regression analysis, respectively. RESULTS: MET
      amplification occurred in 4 (3.5%) of 113 patients, whereas nonsynonomous
      nucleotide variations were present in 9 (7.4%) of 122 patients. No patients
      exhibited concomitant amplification and variation. MET variations were observed
      only in white women with high-grade ovarian tumors, whereas amplifications were
      observed in both black and white women with high-grade serous ovarian primary
      tumors. No patients (n=4) exhibiting a MET alteration achieved an objective
      response when treated on a c-Met inhibitor phase I trial. In addition, ovarian
      cancer patients treated with a c-Met inhibitor with multikinase activity trended
      towards a longer time-to-failure compared with those treated with a c-Met
      specific inhibitor (median: 1.5 vs. 4.5 months, p=0.07). CONCLUSIONS: MET
      alterations occur in a minority of patients with ovarian cancer. c-Met inhibitors
      with multikinase activity may exhibit less activity in ovarian cancer than c-Met
      specific drugs. These findings warrant further investigation.

PMID- 25593980
TI  - Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions
      of the breast.
AB  - Cancer/testis (CT) genes represent a unique class of genes, which are expressed
      by germ cells, normally silenced in somatic cells, but activated in various
      cancers. CT proteins can elicit spontaneous immune responses in cancer patients
      and this feature makes them attractive targets for immunotherapy-based
      approaches. We have previously reported that CTs are relatively commonly
      expressed in estrogen receptor (ER) negative, high risk carcinomas. In this
      study, we examined the expression of selected CT genes in ductal carcinoma in
      situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of
      the breast. ER negative DCIS were found to be associated with significant CT gene
      expression together with HER2 positivity and a marked stromal immune response. 

PMID- 25593981
TI  - Disulfiram/copper causes redox-related proteotoxicity and concomitant heat shock
      response in ovarian cancer cells that is augmented by auranofin-mediated
      thioredoxin inhibition.
AB  - A valuable strategy to develop new therapeutic options for a variety of diseases
      has been the identification of new targets and applications for already approved
      drugs, the so-called drug repositioning. Recurrent ovarian cancer is a nearly
      incurable malignancy for which new and effective treatments are urgently needed.
      The alcohol-deterring drug disulfiram has been shown to cause preferential cell
      death in a variety of cancer cells. In this study, it is shown that disulfiram
      mediates effective cell death in ovarian cancer cells by promoting a pro
      oxidative intracellular environment in a copper-dependent mechanism. Within few
      hours of application, disulfiram caused irreversible cell damage associated with
      pronounced induction of the inducible heat shock proteins HSP70, HSP40, and
      HSP32. The small heat shock protein HSP27 was found to be covalently dimerized
      via oxidized disulfide bonds and precipitated in para-nuclear protein aggregates.
      Simultaneous inhibition of the cellular thioredoxin system by auranofin further
      enhanced the cytotoxic effect of disulfiram. These data indeed indicate that the
      combination of two approved drugs, the anti-alcoholic disulfiram and the anti
      rheumatic auranofin, may be of interest for the treatment of recurrent and
      genotoxic drug-resistant ovarian cancer by inducing a proteotoxic cell death
      mechanism. 

PMID- 25593982
TI  - Interplay Between HGF/SF-Met-Ras Signaling, Tumor Metabolism and Blood Flow as a
      Potential Target for Breast Cancer Therapy.
AB  - High glucose uptake and increase blood flow is a characteristic of most
      metastatic tumors. Activation of Ras signaling increases glycolytic flux into
      lactate, de novo nucleic acid synthesis and uncoupling of ATP synthase from the
      proton gradient. Met tyrosine kinase receptor signaling upon activation by its
      ligand, hepatocyte growth factor/scatter factor (HGF/SF), increases glycolysis,
      oxidative phosporylation, oxygen consumption, and tumor blood volume. Ras is a
      key factor in Met signaling. Using the Ras inhibitor S-trans,trans
      farnesylthiosalicylic acid (FTS), we investigated interplay between HGF/SF-Met
      Ras signaling, metabolism, and tumor blood-flow regulation. In vitro, HGF/SF
      activated Met increased Ras activity, Erk phosphorylation, cell motility and
      glucose uptake, but did not affect ATP. FTS inhibited basal and HGF/SF-induced
      signaling and cell motility, while further increasing glucose uptake and
      inhibiting ATP production. In vivo, HGF/SF rapidly increased tumor blood volume.
      FTS did not affect basal blood-flow but abolished the HGF/SF effect. Our results
      further demonstrate the complex interplay between growth-factor-receptor
      signaling and cellular and tumor metabolism, as reflected in blood flow.
      Inhibition of Ras signaling does not affect glucose consumption or basal tumor
      blood flow but dramatically decreases ATP synthesis and the HGF/SF induced
      increase in tumor blood volume. These findings demonstrate that the HGF/SF-Met
      Ras pathway critically influences tumor-cell metabolism and tumor blood-flow
      regulation. This pathway could potentially be used to individualize tumor therapy
      based on functional molecular imaging, and for combined signaling/anti-metabolic
      targeted therapy. 

PMID- 25593983
TI  - Retaining the long-survive capacity of Circulating Tumor Cells (CTCs) followed by
      xeno-transplantation: not only from metastatic cancer of the breast but also of
      prostate cancer patients.
AB  - We investigated whether Circulating Tumor Cells (CTCs) isolated from epithelial
      tumors could survive and grow in xenotransplants. To this purpose, EpCAM-positive
      CTCs were enriched by CellSearch platform the only FDA-cleared automated platform
      that quantifies tumor burden in peripheral blood and provides clinical evidence
      of predictive and prognostic value. The CTCs were isolated from metastatic
      prostate (n=6) and breast (n=2) cancer patients. The xenograft assay was
      developed in 8-week-old NOD/SCID mice that were subcutaneously injected with
      increasing amounts of CTCs (ranging from 50 to 3000). Human CTCs were found in 8
      out of 8 murine peripheral blood (muPB) and in 6 out of 8 murine bone marrow
      (muBM) samples, after a median follow-up of 10.3 months. Six out of 8 spleens
      were positive for human cytokeratin. Our assay showed higher successful rate than
      those previously reported in breast cancer and hepatocellular carcinoma. The role
      of EpCAM during carcinogenesis is controversial. The identification of human CTCs
      in muPB, muBM and spleen demonstrates that the EpCAM-positive fraction of CTCs
      retains the migratory capacity. This is the first experimental evidence that as
      few as 50 EpCAM-positive prostate cancer CTCs putatively contain metastasis
      initiating-cells (MIC). 

PMID- 25593985
TI  - Targeting glutamine uptake in AML.

PMID- 25593986
TI  - MicroRNA-in drug resistance.

PMID- 25593984
TI  - Expression profiling of migrated and invaded breast cancer cells predicts early
      metastatic relapse and reveals Kruppel-like factor 9 as a potential suppressor of
      invasive growth in breast cancer.
AB  - Cell motility and invasion initiate metastasis. However, only a subpopulation of
      cancer cells within a tumor will ultimately become invasive. Due to this
      stochastic and transient nature, in an experimental setting, migrating and
      invading cells need to be isolated from the general population in order to study
      the gene expression profiles linked to these processes. This report describes
      microarray analysis on RNA derived from migrated or invaded subpopulations of
      triple negative breast cancer cells in a Transwell set-up, at two different time
      points during motility and invasion, pre-determined as "early" and "late" in real
      time kinetic assessments. Invasion- and migration-related gene expression
      signatures were generated through comparison with non-invasive cells, remaining
      at the upper side of the Transwell membranes. Late-phase signatures of both
      invasion and migration indicated poor prognosis in a series of breast cancer data
      sets. Furthermore, evaluation of the genes constituting the prognostic invasion
      related gene signature revealed Kruppel-like factor 9 (KLF9) as a putative
      suppressor of invasive growth in breast cancer. Next to loss in invasive vs non
      invasive cell lines, KLF9 also showed significantly lower expression levels in
      the "early" invasive cell population, in several public expression data sets and
      in clinical breast cancer samples when compared to normal tissue. Overexpression
      of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion
      and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated
      inversely with mitotic activity in clinical samples, indicating anti
      proliferative effects. 

PMID- 25593987
TI  - Novel LIMK2 Inhibitor Blocks Panc-1 Tumor Growth in a mouse xenograft model.
AB  - LIM kinases (LIMKs) are important cell cytoskeleton regulators that play a
      prominent role in cancer manifestation and neuronal diseases. The LIMK family
      consists of two homologues, LIMK1 and LIMK2, which differ from one another in
      expression profile, intercellular localization, and function. The main substrate
      of LIMK is cofilin, a member of the actin-depolymerizing factor (ADF) protein
      family. When phosphorylated by LIMK, cofilin is inactive. LIMKs play a
      contributory role in several neurodevelopmental disorders and in cancer growth
      and metastasis. We recently reported the development and validation of a novel
      LIMK inhibitor, referred to here as T56-LIMKi, using a combination of
      computational methods and classical biochemistry techniques. Here we report that
      T56-LIMKi inhibits LIMK2 with high specificity, and shows little or no cross
      reactivity with LIMK1. We found that T56-LIMKi decreases phosphorylated cofilin
      (p-cofilin) levels and thus inhibits growth of several cancerous cell lines,
      including those of pancreatic cancer, glioma and schwannoma. Because the most
      promising in-vitro effect of T56-LIMKi was observed in the pancreatic cancer cell
      line Panc-1, we tested the inhibitor on a nude mouse Panc-1 xenograft model. T56
      LIMKi reduced tumor size and p-cofilin levels in the Panc-1 tumors, leading us to
      propose T56-LIMKi as a candidate drug for cancer therapy. 

PMID- 25593988
TI  - Modeling the influence of stromal microenvironment in the selection of ENU
      induced BCR-ABL1 mutants by tyrosine kinase inhibitors.
AB  - Tyrosine kinase inhibitors (TKIs) have profoundly changed the natural history of
      chronic myeloid leukemia (CML). However, acquired resistance to imatinib,
      dasatinib or nilotinib (1(st) and 2(nd) generation TKIs), due in part to BCR-ABL1
      kinase mutations, has been largely described. These drugs are ineffective on the
      T315I gatekeeper substitution, which remains sensitive to 3(rd) generation TKI
      ponatinib. It has recently been suggested that the hematopoietic niche could
      protect leukemic cells from targeted therapy. In order to investigate the role of
      a stromal niche in mutation-related resistance, we developed a niche-based cell
      mutagenesis assay. For this purpose, ENU (N-ethyl-N-nitrosourea)-exposed UT-7
      cells expressing non-mutated or T315I-mutated BCR-ABL1 were cultured with or
      without murine MS-5 stromal cells and in the presence of imatinib, dasatinib,
      nilotinib, or ponatinib. In the assays relative to 1(st) and 2(nd) generation
      TKIs, which were performed on non-mutated BCR-ABL1 cells, our data highlighted
      the increasing efficacy of the latter, but did not reveal any substantial effect
      of the niche. In ponatinib assays performed on both non-mutated and T315I-mutated
      BCR-ABL1 cells, an increased number of resistant clones were observed in the
      presence of MS-5. Present data suggested that T315I mutants need either compound
      mutations (e.g. E255K/T315I) or a stromal niche to escape from ponatinib. Using
      array-comparative genomic hybridization experiments, we found an increased number
      of variations (involving some recurrent chromosome regions) in clones cultured on
      MS-5 feeder. Overall, our study suggests that the hematopoietic niche could play
      a crucial role in conferring resistance to ponatinib, by providing survival
      signals and favoring genetic instability. 

PMID- 25593989
TI  - Melanoma brain colonization involves the emergence of a brain-adaptive phenotype.
AB  - The brain offers a unique microenvironment that plays an important role in the
      establishment and progression of metastasis. However, the molecular determinants
      that promote development of melanoma brain metastases are largely unknown.
      Utilizing two species of immune-compromised animals, with in vivo cultivated
      metastatic tissues along with their corresponding host tissues in a metastasis
      model, we here identify molecular events associated with melanoma brain
      metastases. We find that the transcriptional changes in the melanoma cells, as
      induced by the brain-microenvironment in both host species, reveal the
      opportunistic nature of melanoma in this biological context in rewiring the
      molecular framework of key molecular players with their associated biological
      processes. Specifically, we identify the existence of a neuron-like melanoma
      phenotype, which includes synaptic characteristics and a neurotransmission-like
      circuit involving glutamate. Regulation of gene transcription and neuron-like
      plasticity by Ca(2+)-dependent signaling appear to occur through glutamate
      receptor activation. The brain-adaptive phenotype was found as more prominent in
      the early metastatic growth phases compared to a later phase, emphasizing a
      temporal requirement of critical events in the successful colonization of the
      brain. Analysis of the host tissue uncovered a cooperative inflammatory
      microenvironment formed by activated host cells that permitted melanoma growth at
      the expense of the host organism. Combined experimental and computational
      approaches clearly highlighted genes and signaling pathways being shared with
      neurodegenerative diseases. Importantly, the identification of essential
      molecular networks that operate to promote the brain-adaptive phenotype is of
      clinical relevance, as they represent leads to urgently needed therapeutic
      targets. 

PMID- 25593991
TI  - A framework for genomic biomarker actionability and its use in clinical decision
      making.
AB  - The increasing scope and availability of genetic testing options for patients
      suffering from cancer has raised questions about how to use results of molecular
      diagnostics to inform patient care. For some biomarkers (e.g. BRAF mutations in
      melanoma), standards exist that outline treatments for individuals harboring
      aberrations in the biomarker; however for the vast majority of genomic
      abnormalities, few guidelines exist. Clinical decision making and the therapeutic
      approach for a patient with a given cancer characterized by aberrations in
      different genes may be aided by the use of a biomarker actionability framework
      that provides levels of evidence regarding whether and how a molecular
      abnormality can be considered a therapeutically relevant biomarker. A gene may be
      considered theoretically actionable if it has a basis of actionability, such that
      clinically available drugs can target a gene product that drives the cancer or is
      differentially expressed in tumor versus normal elements. Herein, we discuss a
      possible framework for developing guidelines for actionability, as they relate to
      genomically-based cancer therapeutics. 

PMID- 25593992
TI  - PCTAIRE1 regulates p27 stability, apoptosis and tumor growth in malignant
      melanoma.
AB  - PCTAIRE1 is a cyclin-dependent kinase family protein that has been implicated in
      spermatogenesis. Although we recently revealed the function of PCTAIRE1 in
      tumorigenesis of epithelial carcinoma cells, its tumorigenic function in melanoma
      remains unclear. Interrogation of the Oncomine database revealed that malignant
      melanoma showed up-regulation of PCTAIRE1 mRNA compared to normal skin and benign
      melanocytic nevus tissues. In the melanoma cell lines A2058 and SK-MEL-28,
      PCTAIRE1 gene knockdown using siRNA or shRNA diminished melanoma cell
      proliferation as assessed by cellular ATP levels, cell counting and clonogenic
      assays. Moreover, FACS analyses of annexin V-PI staining and DNA content showed
      that PCTAIRE1 knockdown caused apoptosis in A2058 cells. In contrast, PCTAIRE1
      does not appear to be involved in the proliferation of immortalized human
      keratinocyte HaCaT cells. Depletion of PCTAIRE1 by siRNA/shRNA led to p27
      accumulation in melanoma cells but not HaCaT cells. In tumor xenografts of
      melanoma A2058 cells, conditional knockdown of PCTAIRE1 restored p27 protein
      expression and suppressed tumor growth. Our findings reveal a crucial role for
      PCTAIRE1 in regulating p27 protein levels and tumor growth in melanoma cells,
      suggesting that PCTAIRE1 could provide a target for melanoma treatment. 

PMID- 25593993
TI  - Differential regulation of extracellular matrix protein expression in carcinoma
      associated fibroblasts by TGF-beta1 regulates cancer cell spreading but not
      adhesion.
AB  - Cancer progression is characterized by a complex reciprocity between neoplastic
      epithelium and adjacent stromal cells. In ductal carcinoma in situ (DCIS) of the
      breast, both reduced stromal decorin expression and myxoid stroma are correlated
      with increased recurrence risk. In this study, we aimed to investigate paracrine
      regulation of expression of decorin and related extracellular matrix (ECM)
      proteins in cancer-associated fibroblasts (CAFs). Transforming growth factor
      beta1 (TGF-beta1) was identified as a competent ECM modulator, as it reduced
      decorin and strongly enhanced versican, biglycan and type I collagen expression.
      Similar but less pronounced effects were observed when fibroblasts were treated
      with basic fibroblast growth factor (bFGF). Despite this concerted ECM
      modulation, TGF-beta1 and bFGF differentially regulated alpha-smooth muscle actin
      (alpha-SMA) expression, which is often proposed as a CAF-marker. Cancer cell
      derived secretomes induced versican and biglycan expression in fibroblasts.
      Immunohistochemistry on twenty DCIS specimens showed a trend toward periductal
      versican overexpression in DCIS with myxoid stroma. Cancer cell adhesion was
      inhibited by decorin, but not by CAF-derived matrices. Cancer cells presented
      significantly enhanced spreading when seeded on matrices derived from TGF-beta1
      treated CAF. Altogether these data indicate that preinvasive cancerous lesions
      might modulate the composition of surrounding stroma through TGF-beta1 release to
      obtain an invasion-permissive microenvironment. 

PMID- 25593990
TI  - Cross Talk between Two Antioxidant Systems, Thioredoxin and DJ-1: Consequences
      for Cancer.
AB  - Oxidative stress, which is associated with an increased concentration of reactive
      oxygen species (ROS), is involved in the pathogenesis of numerous diseases
      including cancer. In response to increased ROS levels, cellular antioxidant
      molecules such as thioredoxin, peroxiredoxins, glutaredoxins, DJ-1, and
      superoxide dismutases are upregulated to counteract the detrimental effect of
      ROS. However, cancer cells take advantage of upregulated antioxidant molecules
      for protection against ROS-induced cell damage. This review focuses on two
      antioxidant systems, Thioredoxin and DJ-1, which are upregulated in many human
      cancer types, correlating with tumour proliferation, survival, and chemo
      resistance. Thus, both of these antioxidant molecules serve as potential
      molecular targets to treat cancer. However, targeting one of these antioxidants
      alone may not be an effective anti-cancer therapy. Both of these antioxidant
      molecules are interlinked and act on similar downstream targets such as NF
      kappabeta, PTEN, and Nrf2 to exert cytoprotection. Inhibiting either thioredoxin
      or DJ-1 alone may allow the other antioxidant to activate downstream signalling
      cascades leading to tumour cell survival and proliferation. Targeting both
      thioredoxin and DJ-1 in conjunction may completely shut down the antioxidant
      defence system regulated by these molecules. This review focuses on the cross
      talk between thioredoxin and DJ-1 and highlights the importance and consequences
      of targeting thioredoxin and DJ-1 together to develop an effective anti-cancer
      therapeutic strategy. 

PMID- 25593994
TI  - Necroptosis is associated with low procaspase-8 and active RIPK1 and -3 in human
      glioma cells.
AB  - Necroptosis is a regulated necrotic cell death that involves receptor-interacting
      protein kinases RIPK1 and RIPK3. Here, we report that edelfosine triggers a rapid
      and massive cell death in human glioblastoma cells with characteristics of
      necrosis. Only a minor proportion of edelfosine-treated cells underwent caspase
      dependent apoptosis. Autophagy and a rapid influx of extracellular calcium into
      the cells had little impact on cell death. Levels of procaspase-8 were very low
      in necroptosis-prone glioma cells compared with the levels in other cancer cell
      types that underwent apoptosis upon edelfosine treatment. The RIPK1-dependent
      necroptosis inhibitors necrostatin-1 (Nec-1) and Nec-1s as well as siRNA-mediated
      silencing of RIPK3 inhibited edelfosine-induced necroptosis, resulting in
      increased caspase-dependent apoptosis in edelfosine-treated glioblastoma U118
      cells. Inhibition of the RIPK3 substrate MLKL with necrosulfonamide also
      increased apoptosis in edelfosine-treated cells. These data support a major role
      for RIPK1 and RIPK3 in the induction of necrotic cell death and in the switch
      from necrosis to apoptosis following edelfosine treatment. These results indicate
      that the ether lipid edelfosine exerts a rapid necroptotic cell death in
      apoptosis-reluctant glioblastoma cells, suggesting that induction of necroptosis
      could constitute a new approach for glioblastoma therapy. 

PMID- 25593995
TI  - Antagonistic analogs of growth hormone-releasing hormone increase the efficacy of
      treatment of triple negative breast cancer in nude mice with doxorubicin; A
      preclinical study.
AB  - INTRODUCTION: This study evaluated the effects of an antagonistic analog of
      growth hormone-releasing hormone, MIA-602, on tumor growth, response to
      doxorubicin, expression of drug resistance genes, and efflux pump function in
      human triple negative breast cancers. METHODS: HCC1806 (doxorubicin-sensitive)
      and MX-1 (doxorubicin-resistant), cell lines were xenografted into nude mice and
      treated with MIA-602, doxorubicin, or their combination. Tumors were evaluated
      for changes in volume and the expression of the drug resistance genes MDR1 and
      NANOG. In-vitro cell culture assays were used to analyze the effect of MIA-602 on
      efflux pump function. RESULTS: Therapy with MIA-602 significantly reduced tumor
      growth and enhanced the efficacy of doxorubicin in both cell lines. Control
      HCC1806 tumors grew by 435%, while the volume of tumors treated with MIA-602
      enlarged by 172.2% and with doxorubicin by 201.6%. Treatment with the combination
      of MIA-602 and doxorubicin resulted in an increase in volume of only 76.2%.
      Control MX-1 tumors grew by 907%, while tumors treated with MIA-602 enlarged by
      434.8% and with doxorubicin by 815%. The combination of MIA-602 and doxorubicin
      reduced the increase in tumor volume to 256%. Treatment with MIA-602 lowered the
      level of growth hormone-releasing hormone and growth hormone-releasing hormone
      receptors and significantly reduced the expression of multidrug resistance (MDR1)
      gene and the drug resistance regulator NANOG. MIA-602 also suppressed efflux pump
      function in both cell lines. CONCLUSIONS: We conclude that treatment of triple
      negative breast cancers with growth hormone-releasing hormone antagonists reduces
      tumor growth and potentiates the effects of cytotoxic therapy by nullifying drug
      resistance.

PMID- 25593997
TI  - Overcoming EMT-driven therapeutic resistance by BH3 mimetics.
AB  - Epithelial-mesenchymal transition (EMT) contributes to the progression of cancer
      through enhanced invasion and stem-like properties of cancer cells. Additionally,
      EMT confers resistance towards many chemotherapeutics. We recently described a
      mechanism that mediates EMT-driven chemoresistance through augmented levels of
      Bcl-xL, an anti-apoptotic member of the Bcl-2 family (Keitel et al., Oncotarget,
      in press). Here, we elaborate on how these findings pertain to cancer cells
      dispersed in the tumor-adjacent stroma of breast cancer tissues, and how BH3
      mimetics may provide a therapeutic strategy to eliminate cancer cell populations
      that have passed through an EMT. 

PMID- 25593998
TI  - Kallikrein-related peptidase 5 induces miRNA-mediated anti-oncogenic pathways in
      breast cancer.
AB  - Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer.
      Recently, we showed KLK5 reconstitution in breast cancer cell lines suppresses
      malignancy. Present study aims to investigate the functional KLK5 mediated miRNA
      network on breast cancer progression, molecular subtype and survival. 28 miRNAs
      were up-regulated and 62 miRNAs were down-regulated upon KLK5 expression.
      Extracellular matrix (ECM) molecules and cell-adhesion pathways were the most
      significant KLK5-induced miRNA-mediated regulatory targets. Validation from The
      Cancer Genome Atlas (TCGA) database indicated KLK5 was specifically down
      regulated in luminal B and basal-like breast cancer subtypes. There was a
      correlation between KLK5, miRNAs and their downstream ECM gene targets. Long-term
      patient survival correlated with dysregulation of KLK5 and interacting ECM target
      genes. It suggests biological differences between breast cancer molecular
      subtypes, patient survival, and their propensity for invasion and metastasis can
      be explained in part by altered miRNA networks induced by KLK5 dysregulation. We
      provide the first evidence that KLK5 can affect miRNA networks, which regulate
      MMPs and other novel ECM targets and a new compelling hypothesis of interplay
      between serine proteases and miRNAs. We developed a combined KLK5-(ITGB1+COL12A1)
      predictive score for recurrence-free survival that could be exploited in clinical
      applications. 

PMID- 25593999
TI  - MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and
      neck squamous cell carcinoma.
AB  - Little is known about the molecular pathways regulating poor differentiation and
      invasion of head and neck squamous cell carcinoma (HNSCC). In the present study,
      we aimed to determine the role of MDA-9/Syntenin, a metastasis associated
      molecule in HNSCC tumorigenesis. Elevated MDA-9/Syntenin expression was evident
      in 67% (54/81) primary HNSCC tumors (p=0.001-0.002) and 69% (9/13) pre-neoplastic
      tissues (p=0.02-0.03). MDA-9/Syntenin overexpression was associated with the
      stage (p=0.001), grade (p=0.001) and lymph node metastasis (p=0.0001). Silencing
      of MDA-9/Syntenin in 3 poorly differentiated HNSCC cell lines induced squamous
      epithelial cell differentiation, disrupted angiogenesis and reduced tumor growth
      in vitro and in vivo. We confirmed SPRR1B and VEGFR1 as the key molecular targets
      of MDA-9/Syntenin on influencing HNSCC differentiation and angiogenesis
      respectively. MDA-9/Syntenin disrupted SPRR1B expression interacting through its
      PDZ1 domain and altered VEGFR1 expression in vitro and in vivo. VEGFR1 co
      localized with MDA-9/Syntenin in HNSCC cell lines and primary tumor.
      Downregulation of growth regulatory molecules CyclinD1, CDK4, STAT3, PI3K and
      CTNNB1 was also evident in the MDA-9/Syntenin depleted cells, which was reversed
      following over-expression of MDA-9/Syntenin in immortalized oral epithelial
      cells. Our results suggest that early induction of MDA-9/Syntenin expression
      influences HNSCC progression and should be further evaluated for potential
      biomarker development. 

PMID- 25594000
TI  - Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on
      the net charge.
AB  - The majority of known cytotoxic RNases are basic proteins which destroy
      intracellular RNA. Cationization of RNases is considered to be an effective
      strategy for strengthening their antitumor properties. We constructed a set of
      RNase Sa variants consisting of charge reversal mutants, charge neutralization
      mutants, and variants with positively charged cluster at the N-terminus. All
      constructs retain a high level of catalytic activity and differ in net charge.
      Using acute myeloid leukemia cells Kasumi-1 we have shown that (i) cytotoxicity
      of RNase Sa mutants is linearly enhanced by cationization, (ii) the ability of
      cytotoxic mutants to induce cell death is caused by induction of apoptosis and
      (iii) localization of positive charge on N-terminus does not contribute to RNase
      Sa cytotoxicity. Capacity to induce apoptosis in malignant cells and the absence
      of necrotic effects make the RNase Sa mutants with high positive charge a
      suitable anti-cancer agent. 

PMID- 25594001
TI  - Identification of a class of human cancer germline genes with transcriptional
      silencing refractory to the hypomethylating drug 5-aza-2'-deoxycytidine.
AB  - Bona fide germline genes have expression restricted to the germ cells of the
      gonads. Testis-specific germline development-associated genes can become
      activated in cancer cells and can potentially drive the oncogenic process and
      serve as therapeutic/biomarker targets; such germline genes are referred to as
      cancer/testis genes. Many cancer/testis genes are silenced via hypermethylation
      of CpG islands in their associated transcriptional control regions and become
      activated upon treatment with DNA hypomethylating agents; such hypomethylation
      induced activation of cancer/testis genes provides a potential combination
      approach to augment immunotherapeutics. Thus, understanding cancer/testis gene
      regulation is of increasing clinical importance. Previously studied cancer/testis
      gene activation has focused on X chromosome encoded cancer/testis genes. Here we
      find that a sub-set of non-X encoded cancer/testis genes are silenced in non
      germline cells via a mechanism that is refractory to epigenetic dysregulation,
      including treatment with the hypomethylating agent 5-aza-2'-deoxycytidine and the
      histone deacetylase inhibitor tricostatin A. These findings formally indicate
      that there is a sub-group of the clinically important cancer/testis genes that
      are unlikely to be activated in clinical therapeutic approaches using
      hypomethylating agents and it indicates a unique transcriptional silencing
      mechanism for germline genes in non-germline cells that might provide a target
      mechanism for new clinical therapies. 

PMID- 25594002
TI  - Low dose irradiation profoundly affects transcriptome and microRNAme in rat
      mammary gland tissues.
AB  - Ionizing radiation has been successfully used in medical tests and treatment
      therapies for a variety of medical conditions. However, patients and health-care
      workers are greatly concerned about overexposure to medical ionizing radiation
      and possible cancer induction due to frequent mammographies and/or CT scans.
      Diagnostic imaging involves the use of low doses of ionizing radiation, and its
      potential carcinogenic role creates a cancer risk concern for exposed
      individuals. In this study, the effects of X-ray exposure of different doses on
      the gene expression patterns and the micro-RNA expression patterns in normal
      breast tissue were investigated in rats. Our results revealed the activation of
      immune response pathways upon low dose of radiation exposure. These included
      natural killer mediated cytotoxicity pathways, antigen processing and
      presentation pathways, chemokine signaling pathways, and T- and B-cell receptor
      signaling pathways. Both high and low doses of radiation led to miRNA expression
      alterations. Increased expression of miR-34a may be linked to cell cycle arrest
      and apoptosis. Up-regulation of miR-34a was correlated with down-regulation of
      its target E2F3 and up-regulation of p53. This data suggests that ionizing
      radiation at specific high and low doses leads to cell cycle arrest and a
      possible initiation of apoptosis. 

PMID- 25594003
TI  - SirT1 and rRNA in the nucleolus: regulating the regulator.

PMID- 25593996
TI  - Non-coding RNAs in lung cancer.
AB  - The discovery that protein-coding genes represent less than 2% of all human
      genome, and the evidence that more than 90% of it is actively transcribed,
      changed the classical point of view of the central dogma of molecular biology,
      which was always based on the assumption that RNA functions mainly as an
      intermediate bridge between DNA sequences and protein synthesis machinery.
      Accumulating data indicates that non-coding RNAs are involved in different
      physiological processes, providing for the maintenance of cellular homeostasis.
      They are important regulators of gene expression, cellular differentiation,
      proliferation, migration, apoptosis, and stem cell maintenance. Alterations and
      disruptions of their expression or activity have increasingly been associated
      with pathological changes of cancer cells, this evidence and the prospect of
      using these molecules as diagnostic markers and therapeutic targets, make
      currently non-coding RNAs among the most relevant molecules in cancer research.
      In this paper we will provide an overview of non-coding RNA function and
      disruption in lung cancer biology, also focusing on their potential as
      diagnostic, prognostic and predictive biomarkers. 

PMID- 25594004
TI  - Shrewd AKT regulation to survive.

PMID- 25594005
TI  - Achilles' heel of triple negative cancer.

PMID- 25594006
TI  - Altered metabolic pathways in clear cell renal cell carcinoma: A meta-analysis
      and validation study focused on the deregulated genes and their associated
      networks.
AB  - Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal cell
      carcinoma (RCC). It is one of the most therapy-resistant carcinomas, responding
      very poorly or not at all to radiotherapy, hormonal therapy and chemotherapy. A
      more comprehensive understanding of the deregulated pathways in ccRCC can lead to
      the development of new therapies and prognostic markers. We performed a meta-
      analysis of 5 publicly available gene expression datasets and identified a list
      of co- deregulated genes, for which we performed extensive bioinformatic analysis
      coupled with experimental validation on the mRNA level. Gene ontology enrichment
      showed that many proteins are involved in response to hypoxia/oxygen levels and
      positive regulation of the VEGFR signaling pathway. KEGG analysis revealed that
      metabolic pathways are mostly altered in ccRCC. Similarly, Ingenuity Pathway
      Analysis showed that the antigen presentation, inositol metabolism, pentose
      phosphate, glycolysis/gluconeogenesis and fructose/mannose metabolism pathways
      are altered in the disease. Cellular growth, proliferation and carbohydrate
      metabolism, were among the top molecular and cellular functions of the co
      deregulated genes. qRT-PCR validated the deregulated expression of several genes
      in Caki-2 and ACHN cell lines and in a cohort of ccRCC tissues. NNMT and NR3C1
      increased expression was evident in ccRCC biopsies from patients using
      immunohistochemistry. ROC curves evaluated the diagnostic performance of the top
      deregulated genes in each dataset. We show that metabolic pathways are mostly
      deregulated in ccRCC and we highlight those being most responsible in its
      formation. We suggest that these genes are candidate predictive markers of the
      disease. 

PMID- 25594010
TI  - Sirtainties in pancreatic cancer?

PMID- 25594008
TI  - Predictive biomarkers for dasatinib treatment in melanoma.
AB  - Dasatinib has anti-proliferative and anti-invasive effects in melanoma cell
      lines. However clinical trials have shown modest activity for dasatinib in
      metastatic melanoma. Although dasatinib targets SRC kinase, neither expression
      nor phosphorylation of SRC appears to predict response to dasatinib.
      Identification of predictive biomarkers for dasatinib may facilitate selection of
      melanoma patients who are more likely to respond to dasatinib. We correlated the
      anti-proliferative effects of dasatinib in 8 melanoma cell lines with expression
      of a previously identified 6-gene biomarker panel. We examined the relationship
      between response to dasatinib and expression of each gene at both the mRNA and
      protein level. Dasatinib inhibited growth in 3 of the 8 cell lines tested. mRNA
      expression of the panel of 6 biomarkers did not correlate with response, whilst
      elevated protein expression of ANXA1, CAV-1 and EphA2 correlated significantly
      with response to dasatinib in the panel of cell lines. Expression of ANXA1, CAV-1
      and EphA2 were analysed in 124 melanoma samples by immunohistochemistry. ANXA1
      protein was detected in 81 % (97/120) of tumours, CAV-1 in 44 % (54/122) of
      tumours and EphA2 in 74 % (90/121) of tumours. Thirty one % (35/113) of tumours
      tested expressed all three markers and 19 % (21/112) had moderate or strong
      expression of ANXA1, CAV-1 and EphA2. Seventeen percent (19/112) of melanoma
      samples were positive for SRC kinase expression, combined with high expression of
      ANXA1, CAV-1 and EphA2. This subgroup may represent a population of melanoma
      patients who would be more likely to derive clinical benefit from dasatinib
      treatment. 

PMID- 25594009
TI  - Targeting HER2(+) breast cancer: the TBK1/IKKepsilon axis.
AB  - HER2(+) breast cancer (BC) is a highly aggressive subtype, affecting ~20% of BC
      patients. Current treatments include adjuvant or neoadjuvant chemotherapy plus
      anti-HER2 agents such as trastuzumab, a monoclonal antibody directed against
      HER2. Despite improvement in disease free survival, most patients eventually
      succumb to metastatic disease, which is largely incurable. Consequently, there is
      an urgent need to identify novel drugs that can efficiently kill HER2(+) BC
      and/or potentiate the effect of existing anti-HER2 therapies. We performed a
      lenti-viral shRNA kinome screen on non-adherent mouse Her2/Neu tumorspheres and
      identified TBK1, a non-canonical IkappaB kinase (IKK), as the most potent target
      [1]. TBK1 knock-down, or treatment with TBK1-II, a drug that efficiently inhibits
      TBK1 and its close relative IKKepsilon (IKBKE), suppressed growth of human
      HER2(+) BC cells and induced cellular senescence. Senescence was associated with
      inhibition of phosphorylated/active p65-NFkB and induction of the cell cycle
      inhibitor, p16(ink4a). In addition, TBK1-II cooperated with lapatinib, a
      EGFR/HER2 inhibitor, to accelerate apoptosis in vitro and suppress tumor growth
      in a xenograft model of HER2(+) BC. Thus, TBK1/IKKepsilon inhibitors may improve
      treatment of HER2(+) BC in cooperation with anti-HER2 therapy. 

PMID- 25594007
TI  - Highly skewed distribution of miRNAs and proteins between colorectal cancer cells
      and their exosomes following Cetuximab treatment: biomolecular, genetic and
      translational implications.
AB  - Exchange of molecules via exosomes is a means of eukaryotic intercellular
      communication, especially within tumour microenvironments. However, no data are
      available on alterations of exosomal molecular cargo by environmental cues (eg,
      pharmacological treatments). To approach this issue, we compared the abundance of
      754 miRNAs and 741 cancer-related proteins in exosomes secreted by Caco-2
      (Cetuximab-responsive) and HCT- 116 (Cetuximab-resistant) CRC cells, before and
      after Cetuximab treatment, with that in their source cells. Cetuximab
      significantly altered the cargo of Caco-2 exosomes: it increased abundance of
      miRNAs and proteins activating proliferation and inflammation and reduced miRNAs
      and proteins related to immune suppression. These alterations did not precisely
      mirror those in source cells, suggesting a Cetuximab-linked effect. Analogous
      alterations were detected in HCT-116. Transfection of exosomes from Cetuximab
      treated Caco-2 into HCT-116 significantly increased HCT-116 viability;
      conversely, no viability alteration was detected in Caco-2 transfected with
      exosomes from Cetuximab-treated HCT-116. Analysis of networks, comprising targets
      of differentially expressed (DE) exosomal miRNAs and DE exosomal proteins,
      demonstrates a significant involvement of processes related to proliferation,
      inflammation, immune response, apoptosis. Our data extend existing knowledge on
      molecular mechanisms of eukaryotic intercellular communication, especially in
      oncological processes. Their translation to clinical settings may add new weapons
      to existing therapeutic repertoires against cancer.

PMID- 25594011
TI  - Integrin alphaV modulates the cellular pharmacology of copper and cisplatin by
      regulating expression of the influx transporter CTR1.
AB  - The alphaV integrin is expressed in most cancer cells where it regulates a
      diverse array of cellular functions essential to the initiation, progression and
      metastasis of solid tumors. However, little is known about how alphaV integrin
      modulates cellular sensitivity to chemotherapeutic agents, particularly the
      platinum drugs. In this study, we found that down-regulation of alphaV sensitized
      human M21 cells to cisplatin (cDDP) through up-regulation of the copper influx
      transporter CTR1. Cells selected for low alphaV integrin expression (M21L) were
      more sensitive to cDDP, accompanied by increase in CTR1 mRNA and CTR1 protein
      levels, more intracellular cDDP accumulation and cDDP DNA adduct formation. Basal
      copper (Cu) content, Cu uptake, and Cu cytotoxicity were also increased.
      Transfection of a luciferase reporter construct containing the hCTR1 promoter
      sequence revealed an increase of the hCTR1 transcription activity in M21L cells.
      The basis for the increased hCTR1 transcription was related to an increase in the
      steady-state level of Sp1, a transcription factor known to drive hCTR1
      expression. These results indicate that the alphaV integrin modulates sensitivity
      of human cells to the cytotoxic effect of cDDP by regulating expression of the Cu
      transporter CTR1, and introduce the concept that alphaV expression is linked to
      Cu homeostasis. 

PMID- 25594012
TI  - HER2 and HER3 cooperatively regulate cancer cell growth and determine sensitivity
      to the novel investigational EGFR/HER2 kinase inhibitor TAK-285.
AB  - The human epidermal growth factor receptor (HER) family plays a major role in
      cancer cell proliferation. Overexpression of these receptors occurs in various
      cancers, including breast cancer, and correlates with shorter time to relapse and
      lower overall survival. We recently reported that TAK-285, an orally bioavailable
      small molecule inhibitor of HER kinases, is not a p-glycoprotein substrate and
      penetrates the blood-brain barrier, suggesting favorable activity for the
      treatment of brain metastases. To identify the determinants of sensitivity to TAK
      285, we examined the relationship between the IC50 values of TAK-285 for cell
      growth inhibition and the expression of candidate genes that are involved in the
      HER family signaling pathway and trastuzumab resistance in a panel of human
      breast cancer cell lines, other types of cancer cells, and non-transformed cells
      in vitro. These analyses showed an inverse correlation between sensitivity to TAK
      285 (IC50 values) and HER2 or HER3 expression. HER3 was highly phosphorylated in
      TAK-285-sensitive cells, where TAK-285 treatment reduced HER3 phosphorylation
      level. Because HER3 does not possess kinase activity and a selective inhibitor of
      HER2 but not of an epidermal growth factor receptor reduced the phospho-HER3
      level, HER3 was suggested to be trans-phosphorylated by HER2. HER3 knockdown
      using small interfering RNA (siRNA) inhibited cancer cell growth in TAK-285
      sensitive cells but not in TAK-285-insensitive cells. These results suggest that
      HER2 and HER3 mainly regulate cancer cell growth in TAK-285-sensitive cells and
      that phospho-HER3 could be used as a potential molecular marker to select
      patients most likely to respond to TAK-285. 

PMID- 25594013
TI  - Anti-EGFR function of EFEMP1 in glioma cells and patient prognosis.
AB  - EGFR is one of the key oncogenes subjected to targeted therapy for several
      cancers, as it is known to be amplified and/or mutated in up to 40% of malignant
      gliomas. EFEMP1, a fibulin-like extracellular protein, exerts both tumor
      suppressive and oncogenic effects in various cancers and glioma cell models.
      Although EFEMP1's anti-cancer activity has most commonly been attributed to its
      anti-angiogenic effects, we showed for gliomas that EFEMP1's binding to EGFR
      accounts for its suppression of the intracranial tumorigenicity of glioma cells
      expressing high levels of EGFR. In gliomas where EFEMP1 expression, and thus the
      anti-EGFR effect of EFEMP1, was suppressed, heightened levels of EGFR expression
      were associated with unfavorable patient outcomes in prognostic models. Results
      from the current study clearly demonstrate the impact that the anti-EGFR function
      of EFEMP1 has on the expression of EGFR and patient prognosis. A glioma
      prognostic model also suggests EFEMP1's context-dependent oncogenic function in
      gliomas expressing low levels of EGFR. Hence the level of EFEMP1 expression may
      have a predictive value for choosing patients for anti-EGFR therapy. 

PMID- 25594014
TI  - Targeting constitutively-activated STAT3 in hypoxic ovarian cancer, using a novel
      STAT3 inhibitor.
AB  - Tumor hypoxia, a feature of many solid tumors including ovarian cancer, is
      associated with resistance to therapies. We previously demonstrated that hypoxic
      exposure results in increased expression of phosphorylated signal transducer and
      activator of transcription 3 (pSTAT3). We hypothesized the activation of STAT3
      could lead to chemotherapeutic resistance in ovarian cancer cells in hypoxic
      conditions. In this study, we demonstrate the level of pSTAT3 Tyr705 is increased
      in the hypoxic regions of human epithelial ovarian cancer (EOC) specimens, as
      determined by HIF-1alpha and CD-31 staining. In vitro mutagenesis studies proved
      that pSTAT3 Tyr705 is necessary for cell survival and proliferation under hypoxic
      conditions. In addition, we show that S1PR1, a regulator of STAT3 transcription
      via the JAK/STAT pathway, is highly expressed in hypoxic ovarian cancer cells
      (HOCCs). Knock down of S1PR1 in HOCCs reduced pSTAT3 Tyr705 levels and was
      associated with decreased cell survival. Treatment of HOCCs with the STAT3
      inhibitor HO-3867 resulted in a rapid and dramatic decrease in pSTAT3 Tyr705
      levels as a result of ubiquitin proteasome degradation. STAT3-target proteins Bcl
      xL, cyclin D2 and VEGF showed similar decreases in HO-3867 treated cells. Taken
      together, these findings suggest that activation of STAT3 Tyr705 promotes cell
      survival and proliferation in HOCCs, and that S1PR1 is involved in the initiation
      of STAT3 activation. Targeting hypoxia-mediated STAT3 activation represents a
      therapeutic option for ovarian cancer and other solid tumors. 

PMID- 25594015
TI  - A novel role for the SUMO E3 ligase PIAS1 in cancer metastasis.
AB  - Tumor metastasis contributes to the grave morbidity and mortality of cancer, but
      the mechanisms underlying tumor cell invasiveness and metastasis remain
      incompletely understood. Here, we report that expression of the SUMO E3 ligase
      PIAS1 suppresses TGFbeta-induced activation of the matrix metalloproteinase MMP2
      in human breast cancer cells. We also find that knockdown of endogenous PIAS1 or
      inhibition of its SUMO E3 ligase activity stimulates the ability of TGFbeta to
      induce an aggressive phenotype in three-dimensional breast cancer cell organoids.
      Importantly, inhibition of the SUMO E3-ligase activity of PIAS1 in breast cancer
      cells promotes metastases in mice in vivo. Collectively, our findings define a
      novel and critical role for the SUMO E3 ligase PIAS1 in the regulation of the
      invasive and metastatic potential of malignant breast cancer cells. These
      findings advance our understanding of cancer invasiveness and metastasis with
      potential implications for the development of biomarkers and therapies in breast
      cancer. 

PMID- 25594016
TI  - The taxonomy of brain cancer stem cells: what's in a name?
AB  - With the increasing recognition that stem cells play vital roles in the
      formation, maintenance, and potential targeted treatment of brain tumors, there
      has been an exponential increase in basic laboratory and translational research
      on these cell types. However, there are several different classes of stem cells
      germane to brain cancer, each with distinct capabilities and functions. In this
      perspective, we discuss the types of stem cells relevant to brain tumor
      pathogenesis, and suggest a nomenclature for future preclinical and clinical
      investigation. 

PMID- 25594017
TI  - MicroRNA miR-125a-3p modulates molecular pathway of motility and migration in
      prostate cancer cells.
AB  - Fyn kinase is implicated in prostate cancer. We illustrate the role of miR-125a
      3p in cellular pathways accounted for motility and migration of prostate cancer
      cells, probably through its regulation on Fyn expression and Fyn-downstream
      proteins. Prostate cancer PC3 cells were transiently transfected with empty miR
      Vec (control) or with miR-125a-3p. Overexpression of miR-125a-3p reduced
      migration of PC3 cells and increased apoptosis. Live cell confocal imaging
      indicated that overexpression of miR-125a-3p reduced the cells' track speed and
      length and impaired phenotype. Fyn, FAK and paxillin, displayed reduced activity
      following miR-125a-3p overexpression. Accordingly, actin rearrangement and cells'
      protrusion formation were impaired. An inverse correlation between miR-125a-3p
      and Gleason score was observed in human prostate cancer tissues. Our study
      demonstrated that miR-125a-3p may regulate migration of prostate cancer cells. 

PMID- 25594018
TI  - Acellular fraction of ovarian cancer ascites induce apoptosis by activating JNK
      and inducing BRCA1, Fas and FasL expression in ovarian cancer cells.
AB  - Acellular fraction of ascites might play an active role in tumor development.
      Nevertheless the mechanisms involved in the tumor-modulating properties are still
      controversial. Here, we demonstrate that malignant ascites from 8 patients with
      epithelial ovarian cancer did not influence proliferative or invasive properties
      of ovarian cancer cells, but promoted H2O2-induced apoptosis and increased
      sensitivity to paclitaxel. Malignant ascites induced BRCA1, Fas and FasL
      expression and phosphorylation of JNK, but not the activation of caspase pathway.
      Ascites-induced apoptosis of ovarian cancer cells was strongly inhibited by a JNK
      inhibitor suggesting a critical role of JNK pathway in ascite-induced apoptosis.
      The use of siRNA JNK confirmed the importance of JNK in ascites-induced Fas and
      FasL expression. These results demonstrate that malignant ascites induce
      apoptosis of ovarian cancer cells and encourage us to think about the clinical
      management of ovarian cancer patients with malignant ascites. 

PMID- 25594019
TI  - Regulation of circulating endocannabinoids associated with cancer and metastases
      in mice and humans.
AB  - BACKGROUND AND AIMS: Endocannabinoids may modify cancer development, progression
      and associated pain. We determined whether cancer-evoked dysregulations in this
      system become manifest in altered tissue and plasma endocannabinoids. METHODS:
      Endocannabinoid changes due to cancer were explored in a local and metastatic
      syngeneic mouse melanoma model. Endocannabinoid stratification in human cancer
      was cross-sectionally assessed in the plasma of 304 patients (147 men, 157 women,
      aged 32 - 87 years) suffering from several types of cancer at Roman Numeral
      Staging between I and IVc, mostly IV (n = 220), and compared with
      endocannabinoids of healthy controls. RESULTS: In mice with local tumor growth,
      ethanolamide endocannabinoids, i.e., anandamide (AEA), palmitoylethanolamide
      (PEA) and oleoylethanolamide (OEA) were downregulated, whereas 2
      arachidonoylglycerol (2-AG) was increased. Upon spreading of the cancer cells
      particularly 2-AG steadily increased in parallel to disease progression while OEA
      modulated cell migration. Results translated into humans, in whom cancer was
      associated with a decreased AEA, increased 2-AG and increased OEA correlating
      with the number of metastases. CONCLUSIONS: The endocannabinoid system was
      subject to cancer-associated regulations to an extent that led to measurable
      changes in circulating endocannabinoid levels, emphasizing the importance of the
      endocannabinoid system in the pathophysiology of cancer.

PMID- 25594020
TI  - Knock-down of BCL6 / STAT6 sensitizes primary B cell lymphoma cells for treatment
      with current therapeutic agents.
AB  - Primary mediastinal B cell lymphoma (PMBL) is characterized by specific molecular
      hallmarks including the expression of B Cell Lymphoma factor 6 (BCL6) and the
      presence of the activated Signal Transducers and Activators of Transcription
      factor 6 (STAT6). Recently we have shown that combined targeting of BCL6 and
      activated STAT6 by specific chemical inhibitors in PMBL resulted in additive
      efficacy regarding their negative effects on cell viability. Given that despite
      general efficient immuno-chemotherapy in PMBL the delayed treatment-related
      sequelae remains still a main challenge, we analyzed the role of BCL6 and
      activated STAT6 in the sensitivity of PMBL cells to the current treatment
      components. We found that the knock-down of BCL6 / STAT6 by siRNA sensitized the
      PMBL cells to the effects of R-CHOP components in two of three PMBL cell lines.
      In one cell line, MedB-1, which is marked by less expression of BCL6 and mutated
      STAT6, the knock-down of BCL6 / STAT6 did not enhance the efficiency of
      Doxorubicin, Rituximab, and Vincristin. Thus, the targeting of BCL6 and STAT6 in
      addition or prior to the treatment with components of the current immuno
      chemotherapy may sensitize the PMBL tumor cells for drug effects, at least in
      parts of PMBL cases. 

PMID- 25594023
TI  - RB in glutamine metabolism.

PMID- 25594024
TI  - c-FLIP links mTORC2 to apoptosis.

PMID- 25594022
TI  - Polyomavirus BK and prostate cancer: an unworthy scientific effort?
AB  - The Polyomavirus BK (BKV) has been proposed to be one of the possible co-factors
      in the genesis of prostate cancer (PCa) but, so far, the only convincing
      suggestion is the hypothesis of a "hit and run" carcinogenic mechanism induced by
      the virus at early stages of this disease. To support this hypothesis we
      conducted an updated systematic review on previous studies regarding the
      association between BKV and PCa, in order to interpret the contrasting results
      and to explore whether there might be a significant virus-disease link. This
      updated analysis provides evidence for a significant link between BKV expression
      and PCa development, particularly between the BKV infection and the cancer risk.
      Forthcoming scientific efforts that take cue from this study might overcome the
      atavistic and fruitless debate regarding the BKV-PCa association. 

PMID- 25594021
TI  - Damaged mitochondria in Fanconi anemia - an isolated event or a general
      phenomenon?
AB  - Fanconi anemia (FA) is known as an inherited bone marrow failure syndrome
      associated with cancer predisposition and susceptibility to a number of DNA
      damaging stimuli, along with a number of clinical features such as upper limb
      malformations, increased diabetes incidence and typical anomalies in skin
      pigmentation. The proteins encoded by FA-defective genes (FANC proteins) display
      well-established roles in DNA damage and repair pathways. Moreover, some
      independent studies have revealed that mitochondrial dysfunction (MDF) is also
      involved in FA phenotype. Unconfined to FA, we have shown that other syndromes
      featuring DNA damage and repair (such as ataxia-telangiectasia, AT, and Werner
      syndrome, WS) display MDF-related phenotypes, along with oxidative stress (OS)
      that, altogether, may play major roles in these diseases. Experimental and
      clinical studies are warranted in the prospect of future therapies to be focused
      on compounds scavenging reactive oxygen species (ROS) as well as protecting
      mitochondrial functions. 

PMID- 25594025
TI  - NLRs: Sentinels of innate immunity or cancer culprits?

PMID- 25594026
TI  - Luciferase fragment complementation imaging in preclinical cancer studies.
AB  - The luciferase fragment complementation assay (LFCA) enables molecular events to
      be non-invasively imaged in live cells in vitro and in vivo in a comparatively
      cheap and safe manner. It is a development of previous enzyme complementation
      assays in which reporter genes are split into two, individually enzymatically
      inactive, fragments that are able to complement one another upon interaction.
      This complementation can be used to externally visualize cellular activities. In
      recent years, the number of studies which have used LFCAs to probe questions
      relevant to cancer have increased, and this review summarizes the most
      significant and interesting of these. In particular, it focuses on work conducted
      on the epidermal growth factor, nuclear and chemokine receptor families, and
      intracellular signaling pathways, including IP3, cAMP, Akt, cMyc, NRF2 and Rho
      GTPases. LFCAs which have been developed to image DNA methylation and detect RNA
      transcripts are also discussed. 

PMID- 25594027
TI  - SOX15 and other SOX family members are important mediators of tumorigenesis in
      multiple cancer types.
AB  - SOX genes are transcription factors with important roles in embryonic development
      and carcinogenesis. The SOX family of 20 genes is responsible for regulating
      lineage and tissue specific gene expression patterns, controlling numerous
      developmental processes including cell differentiation, sex determination, and
      organogenesis. As is the case with many genes involved in regulating development,
      SOX genes are frequently deregulated in cancer. In this perspective we provide a
      brief overview of how SOX proteins can promote or suppress cancer growth. We also
      present a pan-cancer analysis of aberrant SOX gene expression and highlight
      potential molecular mechanisms responsible for their disruption in cancer. Our
      analyses indicate the prominence of SOX deregulation in different cancer types
      and reveal potential roles for SOX genes not previously described in cancer.
      Finally, we summarize our recent identification of SOX15 as a candidate tumor
      suppressor in pancreatic cancer and propose several research avenues to pursue to
      further delineate the emerging role of SOX15 in development and carcinogenesis. 

PMID- 25594028
TI  - The atypical cell cycle regulator Spy1 suppresses differentiation of the
      neuroblastoma stem cell population.
AB  - Neuroblastoma is an aggressive pediatric cancer originating embryonically from
      the neural crest. The heterogeneity of the disease, as most solid tumors,
      complicates diagnosis and treatment. In neuroblastoma this heterogeneity is well
      represented in both primary tumours and derived cell lines and has been shown to
      be driven by a population of stem-like tumour initiating cells. Resolving the
      molecular mediators driving the division of this population of cells may indicate
      effective therapeutic options for neuroblastoma patients. This study has
      determined that the atypical cyclin-like protein Spy1, recently indicated in
      driving symmetric division of glioma stem cells, is a critical factor in the stem
      like properties of neuroblastoma tumor initiating cell populations. Spy1
      activates Cyclin Dependent Kinases (CDK) in a manner that is unique from
      classical cyclins. Hence this discovery may represent an important opportunity to
      design CDK inhibitor drugs to uniquely target subpopulations of cells within
      these aggressive neural tumours. 

PMID- 25594029
TI  - A novel cohort of cancer-testis biomarker genes revealed through meta-analysis of
      clinical data sets.
AB  - The identification of cancer-specific biomolecules is of fundamental importance
      to the development of diagnostic and/or prognostic markers, which may also serve
      as therapeutic targets. Some antigenic proteins are only normally present in male
      gametogenic tissues in the testis and not in normal somatic cells. When these
      proteins are aberrantly produced in cancer they are referred to as cancer/testis
      (CT) antigens (CTAs). Some CTA genes have been proven to encode immunogenic
      proteins that have been used as successful immunotherapy targets for various
      forms of cancer and have been implicated as drug targets. Here, a targeted in
      silico analysis of cancer expressed sequence tag (EST) data sets resulted in the
      identification of a significant number of novel CT genes. The expression profiles
      of these genes were validated in a range of normal and cancerous cell types.
      Subsequent meta-analysis of gene expression microarray data sets demonstrates
      that these genes are clinically relevant as cancer-specific biomarkers, which
      could pave the way for the discovery of new therapies and/or
      diagnostic/prognostic monitoring technologies. 

PMID- 25594030
TI  - Recurrent ZFX mutations in human sporadic parathyroid adenomas.
AB  - The molecular abnormalities leading to sporadic parathyroid adenomas, a common
      type of human endocrine neoplasm, are heterogeneous and incompletely understood.
      Using whole exome and direct sequencing of parathyroid adenoma DNA samples, we
      identified recurrent somatic mutations in the ZFX gene. ZFX is a member of
      Krueppel C2H2 type zinc finger protein family, was initially described as a
      homolog of ZFY, and has been implicated as a transcription factor regulating
      embryonic stem cell renewal. The ZFX mutations we identified were strikingly
      specific, focused in each tumor on one encoded residue in a hotspot of two
      consecutive highly conserved arginine residues (R786/787; arginine to glutamine,
      threonine or leucine) in a zinc finger domain near the C-terminus of the protein.
      The intragenic specificity of these recurrently selected mutations, their
      confirmed expression within the tumors, the absence of loss of heterozygosity,
      and the absence of these mutations among over 4000 ZFX alleles in the dbSNP137
      database, strongly suggest a novel role for ZFX as a human proto-oncogene.
      Further, these observations highlight the mutated zinc-finger domain as a new
      focal point for understanding ZFX's normal and tumorigenic functions, and for
      development of molecularly-targeted therapeutics. 

PMID- 25594031
TI  - Hypomethylation and increased expression of the putative oncogene ELMO3 are
      associated with lung cancer development and metastases formation.
AB  - Numerous genetic and epigenetic events driving tumorigenesis have been
      characterized. However, knowledge is lacking on the particular events required
      for the metastatic spread of cancer cells. The engulfment and cell motility 3
      (ELMO3) gene plays an important role for the migratory potential of cells, but
      have not previously been studied in primary samples from cancer patients. We
      collected material from primary non-small cell lung cancer (NSCLC) tumors and
      paired brain or adrenal gland metastases from 26 patients and from 26 primary
      tumor samples from metastasis-free patients matched for age, gender, histology, T
      stage, smoking status, and proportion of tumor cells. Using reverse transcriptase
      quantitative PCR (RT-qPCR) ELMO3 was shown to be overexpressed in primary tumors
      from patients with distant metastases compared to normal lung tissue (p<0.001),
      and compared to primary tumors from metastasis-free patients (p<0.001). The
      increased expression coincided with decreased methylation levels of the ELMO3
      promoter region. High expression and hypomethylation of ELMO3 were also observed
      when studying the paired brain and adrenal gland metastases. In conclusion, the
      putative oncogene, ELMO3, is overexpressed in NSCLC in combination with
      hypomethylation of its promoter and these cancer-specific events are associated
      with the formation of metastases. 

PMID- 25594032
TI  - PICT1 expression is a poor prognostic factor in non-small cell lung cancer.
AB  - PICT1 is a key regulator of the MDM2-TP53 pathway. High mRNA expression levels of
      PICT1 are associated with poor prognosis in several cancers with wild-type TP53.
      In this study, we identified the PICT1 protein expression profile in non-small
      cell lung cancer (NSCLC) with wild-type TP53 in the nucleolus and cytoplasm, and
      revealed the relationship between PICT1 expression and patient
      clinicopathological factors. PICT1 expression in the tumor cells of 96 NSCLC
      patients with wild-type TP53 was evaluated by immunohistochemistry. Forty-three
      of 96 (44.8%) NSCLC samples were positive for nucleolar PICT1, while 40/96
      (41.7%) NSCLC samples were positive for cytoplasmic PICT1. There was no
      correlation between nucleolar PICT1 expression and clinicopathological factors.
      However, cytoplasmic PICT1 expression was significantly correlated with sex,
      smoking history, differentiation, lymphatic invasion and pathological stage. In
      multivariate analysis, lymphatic invasion was significantly associated with
      cytoplasmic PICT1 expression (hazard ratio: 5.02, P = 0.026). We scrutinized
      PICT1 expression in samples of NSCLC with wild-type TP53, and showed a
      correlation between cytoplasmic PICT1 expression and several clinicopathological
      factors in these patients. Our results indicate that cytoplasmic PICT1 expression
      is a poor prognostic factor and is associated with tumor progression via
      lymphatic invasion in these patients. 

PMID- 25594033
TI  - BRCA1 and gammaH2AX as independent prognostic markers in oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinomas (OSCC) are believed to originate from sequential
      mutations that can develop as a consequence of genetic instability acquired over
      time. BRCA1 are linked to DNA recombination and repair processes, being of
      importance for its role in regulation of RAD51 and H2AX (gammaH2AX). The aim of
      this study was to investigate the relationship between BRCA1 expression status
      and evaluate its prognostic impact. We selected from 150 OSCC patients, and
      evaluated BRCA1 expression in OSCC by immunohistochemistry and qRT-PCR, comparing
      its expression with homologous recombination markers (RAD51, gammaH2AX and p53),
      clinicopathological and survival data. Expression of BRCA1 was observed in 61
      cases (43.88%) and was related to tumor size (T stage) (p=0.001), and gender
      (p=0.017). mRNA from BRCA1 showed a borderline relationship with perineural
      invasion (p=0.053). BRCA1 [p=0.030; HR: 2.334 (C.I.: 1.087-5.012)], gammaH2AX
      [p=0.045; HR: 0.467 (C.I.: 0.222-0.628)] and gender [p=0.001; HR: 10.386 [(C.I.:
      2.679-10.623)] were independent prognostic factors for DSS. BRCA1 and gammaH2AX
      expression by OSCC cells are associated with reduced overall survival time,
      independent of other variables in patients, as well as gender, and our findings
      shed some light about DSB markers in OSCC and its role as prognostic factors. 

PMID- 25594034
TI  - Peroxiredoxin 6 in skin carcinogenesis.

PMID- 25594035
TI  - ITCH E3 ligase in ATM network.

PMID- 25594036
TI  - Tumor suppressor prostaglandin D2.

PMID- 25594037
TI  - E-FABP: regulator of immune function.

PMID- 25594038
TI  - Genetic pathways, prevention, and treatment of sporadic colorectal cancer.
AB  - Epithelial cancer of the colon and rectum, also known as colorectal cancer (CRC),
      results from a progressive accumulation of genetic and epigenetic alterations
      that lead to uncontrolled growth of colonocytes, the cells lining the colon and
      rectum. CRC is the second leading cause of cancer-related deaths and the third
      most common cancer in men and in women in the U.S. Of all the patients diagnosed
      with CRC every year, it is estimated that the vast majority of CRCs are non
      hereditary "sporadic cancers" with no apparent evidence of an inherited
      component. Sporadic CRC results from the cumulative effects of multiple genetic
      and epigenetic alterations caused by somatic mutations, which may themselves be
      the indirect result of several environmental factors. This review examines our
      current understanding of the major genetic alterations leading to colon cancer,
      options for prevention and early detection of CRC, and the currently available
      treatment approaches that may target these different genetic alterations. 

PMID- 25594040
TI  - Resistance to c-Kit inhibitors in melanoma: insights for future therapies.
AB  - Mutations activating the receptor tyrosine kinase c-Kit occur commonly in
      melanomas arising on mucosal membranes and acral skin. Clinical studies have
      demonstrated that selective inhibition of c-Kit is effective in treating patients
      with c-Kit mutant gastrointestinal stromal tumors, but c-Kit inhibitor activity
      has been disappointing in c-Kit mutant melanoma patients. Activated c-Kit
      utilises phosphatidylinositol 3-kinase (PI3K) signalling as the dominant effector
      of cell proliferation and survival with the mitogen-activated protein kinase
      (MAPK) cascade serving as an ancillary survival pathway. We confirmed that these
      pathways are re-activated in melanoma cells with acquired resistance to c-Kit
      inhibitors and that these resistant sublines remain sensitive to the concurrent
      inhibition of MAPK and PI3K signalling. These findings suggest that durable
      responses in c-Kit mutant melanoma may require combination therapies that
      selectively inhibit critical downstream proliferative and survival pathways. We
      also discuss the interaction between targeted therapies and anti-tumor immune
      responses and the need to consider immunotherapies in new combinatorial treatment
      approaches. 

PMID- 25594039
TI  - Necrosis, and then stress induced necrosis-like cell death, but not apoptosis,
      should be the preferred cell death mode for chemotherapy: clearance of a few
      misconceptions.
AB  - Cell death overarches carcinogenesis and is a center of cancer researches,
      especially therapy studies. There have been many nomenclatures on cell death, but
      only three cell death modes are genuine, i.e. apoptosis, necrosis and stress
      induced cell death (SICD). Like apoptosis, SICD is programmed. Like necrosis,
      SICD is a pathological event and may trigger regeneration and scar formation.
      Therefore, SICD has subtypes of stress-induced apoptosis-like cell death (SIaLCD)
      and stress-induced necrosis-like cell death (SInLCD). Whereas apoptosis removes
      redundant but healthy cells, SICD removes useful but ill or damaged cells. Many
      studies on cell death involve cancer tissues that resemble parasites in the host
      patients, which is a complicated system as it involves immune clearance of the
      alien cancer cells by the host. Cancer resembles an evolutionarily lower-level
      organism having a weaker apoptosis potential and poorer DNA repair mechanisms.
      Hence, targeting apoptosis for cancer therapy, i.e. killing via SIaLCD, will be
      less efficacious and more toxic. On the other hand, necrosis of cancer cells
      releases cellular debris and components to stimulate immune function, thus
      counteracting therapy-caused immune suppression and making necrosis better than
      SIaLCD for chemo drug development. 

PMID- 25594042
TI  - Low intensity focused ultrasound (LOFU) modulates unfolded protein response and
      sensitizes prostate cancer to 17AAG.
AB  - The hypoxic tumor microenvironment generates oxidative Endoplasmic Reticulum (ER)
      stress, resulting in protein misfolding and unfolded protein response (UPR). UPR
      induces several molecular chaperones including heat-shock protein 90 (HSP90),
      which corrects protein misfolding and improves survival of cancer cells and
      resistance to tumoricidal therapy although prolonged activation of UPR induces
      cell death. The HSP90 inhibitor, 17AAG, has shown promise against various solid
      tumors, including prostate cancer (PC). However, therapeutic doses of 17AAG
      elicit systemic toxicity. In this manuscript, we describe a new paradigm where
      the combination therapy of a non-ablative and non-invasive low energy focused
      ultrasound (LOFU) and a non-toxic, low dose 17AAG causes synthetic lethality and
      significant tumoricidal effects in mouse and human PC xenografts. LOFU induces ER
      stress and UPR in tumor cells without inducing cell death. Treatment with a non
      toxic dose of 17AAG further increased ER stress in LOFU treated PC and switch UPR
      from a cytoprotective to an apoptotic response in tumors resulting significant
      induction of apoptosis and tumor growth retardation. These observations suggest
      that LOFU-induced ER stress makes the ultrasound-treated tumors more susceptible
      to chemotherapeutic agents, such as 17AAG. Thus, a novel therapy of LOFU-induced
      chemosensitization may be designed for locally advanced and recurrent tumors. 

PMID- 25594041
TI  - microRNAs: short non-coding bullets of gain of function mutant p53 proteins.
AB  - TP53 gene mutations are present in more than half of all human cancers. The
      resulting proteins are mostly full-length with a single aminoacid change and are
      abundantly present in cancer cells. Some of mutant p53 proteins gain oncogenic
      activities through which actively contribute to the aberrant cell proliferation,
      increased resistance to apoptotic stimuli and ability to metastatize of cancer
      cells. Gain of function mutant p53 proteins can transcriptionally regulate the
      expression of a large plethora of target genes. This mainly occurs through the
      formation of oncogenic transcriptional competent complexes that include mutant
      p53 protein, known transcription factors, posttranslational modifiers and
      scaffold proteins. Mutant p53 protein can also transcriptionally regulate the
      expression of microRNAs, small non-coding RNAs that regulate gene expression at
      the posttranscriptional level. Each microRNA can putatively target the expression
      of hundred mRNAs and consequently impact on many cellular functions. Thus, gain
      of function mutant p53 proteins can exert their oncogenic activities through the
      modulation of both non-coding and coding regions of human genome. 

PMID- 25594043
TI  - AMP-activated protein kinase (AMPK) as a potential therapeutic target independent
      of PI3K/Akt signaling in prostate cancer.
AB  - Depletion of cellular energy activates the AMP-activated kinase (AMPK) to favor
      energy-producing catabolic processes during tumorigenesis. Using a panel of in
      vitro cell lines and resected tumors, we investigated the therapeutic value of
      manipulating AMPK in prostate cancer (PC). Phospho-AMPK expression was
      significantly elevated in human PC cells and clinical PC samples. In clinical PC,
      we observed a trend for increasing phospho-AMPK with increasing Gleason sum
      score; Phospho-AMPK expression was associated with phospho-ACC (p=0.0023). Using
      the paired PC3 and PC3M cells to model progressive androgen-independent PC,
      treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR) or A-769662
      suppressed proliferation, migration and invasion in both cell lines, and down
      regulated mTOR and P70S6Ki levels regardless of the Akt status. Involvement of
      AMPK was confirmed by Compound C (AMPK inhibitor) and siRNA-mediated AMPK
      silencing. Despite similar functional responses in PC3 and PC3M cells, AMPK
      activation resulted in sustained phospho-Akt activation in PC3M cells, but not in
      PC3 cells. This prompted the addition of the PI3K inhibitor LY-294002 to AICAR
      treatment of PC3M cells in a proliferation assay. Interestingly, we found no
      synergistic effects upon combined treatment. Collectively, these findings support
      AMPK as a potential therapeutic target independent of PI3K/Akt signalling. 

PMID- 25594046
TI  - NMI and EMT.

PMID- 25594044
TI  - Effects of octreotide and insulin on colon cancer cellular proliferation and
      correlation with hTERT activity.
AB  - Peptide hormone somatostatin and its receptors have a wide range of physiological
      functions and play a role in the treatment of numerous human diseases, including
      colorectal cancer. Octreotide, a synthetic somatostatin-analog peptide, inhibits
      growth of colonic cancer cells primarily by binding to G-protein coupled
      receptors and elicits cellular responses through second-messenger systems.
      Insulin also initiates mitogenic signals in certain cell types. The objective of
      the present study was to explore the effects of octreotide with or without
      insulin treatment, on Caco-2 and HT-29 human colon-cancer cell proliferation and
      to correlate their effects with the activation of telomerase reverse
      transcriptase (hTERT). The involvement of protein tyrosine phosphatases in the
      regulation of the anti-proliferative effect of octreotide was also evaluated.
      Sodium orthovanadate was used to reverse the anti- proliferative effect of
      octreotide. Telomerase activity was determined for each time point under
      octreotide and/or insulin treatment. Elevated expression of sst1, sst2 and sst5
      was confirmed in both cell lines by RT-PCR. Immunocytochemistry detected sst1,
      sst2A, sst2B, sst3, sst4 and sst5 protein expression in the membranes of both
      cell lines. Octreotide inhibited the proliferation of Caco-2 and HT-29 cells in a
      time and dose-dependent manner. Insulin exerted proliferative effects in Caco-2
      cells and octreotide reversed its effect in both cell lines. Sodium orthovanadate
      suppressed the anti-proliferative effect of octreotide both in Caco-2 and HT-29
      cells. Telomerase activity was significantly reduced when Caco-2 cells were
      exposed to octreotide, under serum-free cultured medium. On the other hand,
      telomerase attenuation after octreotide treatment could not counteract the
      actions of insulin on both cells. Our data indicate that the use of octreotide
      could provide a possible therapeutic approach to the management of certain
      patients who suffer from colon cancer. 

PMID- 25594045
TI  - Helicobacter pylori-induced STAT3 activation and signalling network in gastric
      cancer.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is the most important gastric
      carcinogen. However, the mechanisms of H. pylori induced gastric carcinogenesis
      through STAT3 activation are largely unknown. We evaluated the effects of H.
      pylori infection on STAT3 activation and dissected the signalling network of
      STAT3 in H. pylori- infected gastric carcinogenesis. METHODS: The expression of
      phospho-STAT3 (pSTAT3) was evaluated by immunohistochemistry and western blot.
      Gene expression array and chromatin immunoprecipitation were used to dissect the
      STAT3 signalling network on H. pylori co-cultured AGS. RESULTS: pSTAT3 was
      significantly higher in H. pylori -positive gastritis than in H. pylori -negative
      gastritis ( P = 0.003). In addition, 98% of H. pylori positive intestinal
      metaplasia specimens showed STAT3 activation, whereas pSTAT3 was significantly
      decreased in all 43 specimens one year after H. pylori eradication ( P < 0.001).
      Moreover, pSTAT3 was only detected in the H. pylori -infected gastric tissues of
      mice but not in control mice. We further identified 6 candidates ( BRUNOL4,
      FGFR1, SHOX2, JAK3, MAPK8, and PDPN ) were directly up-regulated by H. pylori
      induced STAT3 activation. CONCLUSION: H. pylori infection triggers the activation
      of STAT3 and de-regulates multitude of tumorigenic genes which may contribute to
      the initiation and progression of gastric cancer.

PMID- 25594047
TI  - P-gp and taxanes.

PMID- 25594048
TI  - YAP as oncotarget in uveal melanoma.

PMID- 25594049
TI  - Sources of CNS tumor heterogeneity.

PMID- 25594050
TI  - Targeting protein synthesis in cancer cells.

PMID- 25594052
TI  - The combinatorial complexity of cancer precision medicine.
AB  - Precision medicine approaches have recently been developed that offer therapies
      targeting mainly single genetic alterations in malignant tumors. However, next
      generation sequencing studies have shown that tumors normally harbor multiple
      genetic alterations, which could explain the so far limited successes of
      personalized medicine, despite considerable benefits in certain cases.
      Combination therapies may contribute to a solution, but will pose a major
      challenge for clinical trials evaluating those therapies. As we discuss here,
      reasons include the low abundance of most of the relevant mutations and
      particularly the combinatorial complexity of possible combination therapies. Our
      report provides a systematic and quantitative account of the implications of
      combinatorial complexity for cancer precision medicine and clinical trial design.
      We also present an outlook on how systems biological approaches may be harnessed
      to contribute to a solution of the complexity challenge by predicting optimal
      combination therapies for individual patients and how clinical trial design may
      be adapted by combining and extending basket and umbrella design features. 

PMID- 25594055
TI  - Hypoxia regulates RNA splicing of HIF targets.

PMID- 25594054
TI  - MicroRNA-17 inhibits tumor growth by stimulating T-cell mediated host immune
      response.
AB  - BACKGROUND: Melanoma is one of the fastest-rising types of cancer in North
      American. Accumulating evidence suggests that anti-tumor immune tolerance plays a
      critical role in tumor development. METHODS: B16 melanoma cells were injected
      into wild type and miR-17 overexpressing transgenic mice. Tumor growth was
      monitored and tumor bearing mice were sacrificed by the end of the forth week.
      Peripheral blood and spleen cells were subject to flow cytometry analysis and
      tumor samples were subject to immunohistochemistry staining. Meanwhile, Jurkat
      cells transfected with mock-control or miR-17 overexpressing plasmid were co
      cultured with B16 cells. The influence of miR-17 on cell cycle, proliferation and
      survival was evaluated. RESULTS: The melanoma tumors formed in mice
      overexpressing miR-17 were less than that in wild type mice. In addition, the miR
      17 tumors were less invasive and less angiogenic. The percentage of CD8+ T cells
      was suppressed in miR-17 transgenic mice before melanoma cell injection. Its
      level was significantly increased upon tumor grafting. More tumor infiltrating
      CD8+ cytotoxic T lymphocyte could be found in transgenic mice with tumor
      formation. Luciferase assay and protein analysis indicated that STAT3 was the
      target of miR-17. Decreased levels of STAT3 were associated with miR-17 over
      expression. Down-regulation of STAT3 in Jurkat cells promoted cell proliferation
      and mitosis. CONCLUSIONS: MiR-17 inhibits melanoma growth by stimulating CD8+ T
      cells mediated host immune response, which is due to its regulation of STAT3.

PMID- 25594056
TI  - Liver pro-oncogenic potential of SERPINB3.

PMID- 25594051
TI  - Adaptors for disorders of the brain? The cancer signaling proteins NEDD9, CASS4,
      and PTK2B in Alzheimer's disease.
AB  - No treatment strategies effectively limit the progression of Alzheimer's disease
      (AD), a common and debilitating neurodegenerative disorder. The absence of viable
      treatment options reflects the fact that the pathophysiology and genotypic causes
      of the disease are not well understood. The advent of genome-wide association
      studies (GWAS) has made it possible to broadly investigate genotypic alterations
      driving phenotypic occurrences. Recent studies have associated single nucleotide
      polymorphisms (SNPs) in two paralogous scaffolding proteins, NEDD9 and CASS4, and
      the kinase PTK2B, with susceptibility to late-onset AD (LOAD). Intriguingly,
      NEDD9, CASS4, and PTK2B have been much studied as interacting partners regulating
      oncogenesis and metastasis, and all three are known to be active in the brain
      during development and in cancer. However, to date, the majority of studies of
      these proteins have emphasized their roles in the directly cancer relevant
      processes of migration and survival signaling. We here discuss evidence for roles
      of NEDD9, CASS4 and PTK2B in additional processes, including hypoxia, vascular
      changes, inflammation, microtubule stabilization and calcium signaling, as
      potentially relevant to the pathogenesis of LOAD. Reciprocally, these functions
      can better inform our understanding of the action of NEDD9, CASS4 and PTK2B in
      cancer. 

PMID- 25594053
TI  - Genomic quantitative real-time PCR proves residual disease positivity in more
      than 30% samples with negative mRNA-based qRT-PCR in Chronic Myeloid Leukemia.
AB  - Imatinib mesylate (IM) is the first line therapy against Chronic Myeloid
      Leukemia, effectively prolonging overall survival. Because discontinuation of
      treatment is associated with relapse, IM is required indefinitely to maintain
      operational cure. To assess minimal residual disease, cytogenetic analysis is
      insensitive in a high background of normal lymphocytes. The qRT-PCR provides
      highly sensitive detection of BCR-ABL1 transcripts, but mRNA levels are not
      directly related to the number of leukemic cells, and undetectable results are
      difficult to interpret. We developed a sensitive approach to detect the number of
      leukemic cells by a genomic DNA (gDNA) Q-PCR assay based on the break-point
      sequence, with a formula to calculate the number of Ph-positive cells. We
      monitored 8 CML patients treated with IM for more than 8 years. We tested each
      samples by patient specific gDNA Q-PCR in parallel by the conventional
      techniques. In all samples positive for chimeric transcripts we showed
      corresponding chimeric gDNA by Q-PCR, and in 32.8% (42/128) of samples with
      undetectable levels of mRNA we detected the persistence of leukemic cells. The
      gDNA Q-PCR assay could be a new diagnostic tool used in parallel to conventional
      techniques to support the clinician's decision to vary or to STOP IM therapy. 

PMID- 25594058
TI  - Rac1 as a multifunctional therapeutic target to prevent and combat cancer
      metastasis.
AB  - Metastatic progression of malignant tumors resistant to conventional therapeutic
      approaches is an ultimate challenge in clinical oncology. Despite the efforts of
      basic and clinical researchers, there is still no effective treatment schedule to
      prevent or combat metastatic spread of malignant tumors. This report presents
      recent findings that could help in the development of targeted therapeutics
      directed against the most aggressive and treatment-resistant carcinoma cells. It
      was demonstrated that HNSCC carcinoma cell lines with acquired treatment
      resistance possessed increased number of cells with carcinoma stem cell (CSC)
      properties. Furthermore, resistant cells were characterized by increased
      expression of Rac1, enhanced cell migration, and accelerated release of proangio-
      and vasculogenic factors (VEGF-A) and influence on endothelial cell (HMEC-1)
      migration. Inhibition of Rac1 signaling in the treatment-resistant carcinoma
      cells can interrupt metastatic process due to anoikis restoration and decrease of
      cell migration. It is also suggested that carcinoma cells with repressed survival
      capacities will be characterized by reduced release of proangiogenic factors,
      resulting in the decrease of endothelial cell migration. Therefore targeting of
      Rac1-related pathways may be considered as a promising therapeutic approach to
      prevent or combat metastatic lesions. 

PMID- 25594057
TI  - Pathways driving the endocytosis of mutant and wild-type EGFR in cancer.
AB  - EGFR (epidermal growth factor receptor) is activated through changes in
      expression or mutations in a number of tumors and is a driving force in cancer
      progression. EGFR is targeted by numerous inhibitors, including chimeric
      antibodies targeting the extracellular domain and small molecule kinase domain
      inhibitors. The kinase domain inhibitors are particularly active against mutant
      forms of the receptor, and subsequent mutations drive resistance to the
      inhibitors. Here, we review recent developments on the trafficking of wild-type
      and mutant EGFR, focusing on the roles of MIG6, SPRY2, ITSN, SHP2, S2R(PGRMC1)
      and RAK. Some classes of EGFR regulators affect wild-type and mutant EGFR
      equally, while others are specific for either the wild-type or mutant form of the
      receptor. Below we summarize multiple signaling-associated pathways that are
      important in trafficking wild-type and mutant EGFR with the goal being
      stimulation of new approaches for targeting the distinct forms of the receptor. 

PMID- 25594059
TI  - Epidermal growth factor receptor (EGFR) mutations are exceptionally rare in
      thyroid transcription factor (TTF-1)-negative adenocarcinomas of the lung.
AB  - INTRODUCTION: Approximately 70% of lung adenocarcinomas express TTF-1. EGFR
      mutations are present in 13-15% of Western adenocarcinoma patients. This paper
      investigates TTF1 as a negative predictor of mutant EGFR in lung adenocarcinomas.
      RESULTS: In the pilot cohort (N = 301) two of 224 specimens positive for EGFR
      mutations had negative TTF-1 expression (sensitivity 99.1%, 95% confidence
      interval (CI) 96.8-99.9%). Estimated negative predictive values (NPV) for EGFR
      mutation prevalence rates of 13% and 15% are 99.5% (95% credible interval (CRI)
      98.6%-99.9%) and 99.4% (CRI - 98.4%-99.9%). For EGFR mutation rates of 13% and
      15%, using validation cohort data (211 patients), the estimated NPVs were 97%
      (95% CRI 92%-99%) and 96% (95% CRI 91%-99%). METHODS: Formalin-fixed paraffin
      embedded tumors from lung adenocarcinoma patients were analyzed for EGFR
      mutations by allele-specific PCR in the 'pilot cohort'. TTF-1 status was
      documented as positive or negative. Negative predictive value (NPV) for a range
      of true prevalence of EGFR mutation (1%-50%) was estimated using Bayesian
      modeling. The hypothesis was validated in a separate 'validation' cohort using
      the same modeling. CONCLUSION: An overwhelming majority of TTF-1 negative
      adenocarcinomas will be negative for EGFR mutations. This finding allows for
      earlier initiation of chemotherapy in newly diagnosed TTF-1 negative
      adenocarcinomas of the lung with stage IV disease.

PMID- 25594060
TI  - Up-regulation of anti-apoptotic genes confers resistance to the novel anti
      leukaemic compound PEP005 in primary AML cells.
AB  - We showed previously that PEP005 induced apoptosis in leukaemic cell lines and
      blasts from patients with acute myeloid leukaemia (AML). Here we assess the anti
      leukeamic effects of PEP005 in vivo and determine the mechanism of resistance of
      PEP005 non-responsive cells. We used 2 human xenograft mouse models of AML to
      assess the anti-leukaemic effects of PEP005 in vivo. Expression microarray
      analysis of primary AML blasts following treatment with PEP005 was used to
      determine patterns of gene expression that conferred resistance. PEP005
      significantly reduced tumour burden in two human leukaemia mouse xenograft
      models. We also assessed responsiveness of 33 AML samples to PEP005, with 78% of
      the samples entering apoptosis at 100nM. Resistance to PEP005 was not restricted
      to a particular AML subtype. Expression microarray analysis of resistant samples
      following treatment with PEP005 revealed a significant up regulation of the anti
      apoptotic genes Bcl-2A1, Mcl-1, and PHLDA1 which was verified using RT-PCR. We
      conclude that PEP005 shows broad efficacy against AML subtypes and that up
      regulation of anti-apoptotic genes underlies resistance to this agent and could
      be used to screen for patients unlikely to benefit from a therapeutic regime
      involving PEP005. 

PMID- 25594063
TI  - CD27(+)IgD(-) B cells in the peripheral blood of colorectal cancer patients: on
      anti-tumor or tumor-protective mission?

PMID- 25594062
TI  - Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations
      to clinical and pathological features.
AB  - The cannabinoid receptors are upregulated in many types of cancers, including
      mantle cell lymphoma (MCL) and have been suggested to constitute novel
      therapeutic targets. The expression pattern of the key members of the
      endocannabinoid system was analyzed in a well-characterized MCL patient cohort
      and correlated to biological features. 107 tumor tissues were analyzed for the
      mRNA levels of cannabinoid receptors 1 and 2 (CNR1 and CNR2) and the two main
      enzymes regulating the endocannabinoid anandamide levels in tissue: NAPEPLD and
      FAAH (participating in synthesis and degradation, respectively). NAPEPLD, CNR1
      and CNR2 were overexpressed while FAAH expression was reduced in MCL compared to
      non-malignant B-cells. Both low CNR1 and high FAAH levels correlated with
      lymphocytosis (p=0.016 and p=0.022, respectively) and with leukocytosis (p=0.0018
      and p=0.047). Weak to moderate CNR1 levels were a feature of SOX11 negative MCL
      (p=0.006). Both high CNR2 and high FAAH levels correlated to anemia (p=0.0006 and
      p=0.038, respectively). In conclusion, the relative expression of the anandamide
      synthesizing and metabolizing enzymes in MCL is heavily perturbed. This finding,
      together with high expression of cannabinoid receptors, could favor enhanced
      anandamide signaling and suggest that targeting the endocannabinoid system might
      be considered as part of lymphoma therapy. 

PMID- 25594061
TI  - Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal
      cancer.
AB  - Preclinical studies demonstrate that epidermal growth factor receptor (EGFR)
      signals through both kinase-dependent and independent pathways and that combining
      a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is
      synergistic. We conducted a dose-escalation, phase I study combining erlotinib,
      cetuximab, and bevacizumab. The subset of patients with metastatic colorectal
      cancer was analyzed for safety and antitumor activity. Forty-one patients with
      heavily pretreated metastatic colorectal cancer received treatment on a range of
      dose levels. The most common treatment-related grade >=2 adverse events were rash
      (68%), hypomagnesemia (37%), and fatigue (15%). Thirty of 34 patients (88%)
      treated at the full FDA-approved doses of all three drugs tolerated treatment
      without drug-related dose-limiting effects. Eleven patients (27%) achieved stable
      disease (SD) >=6 months and three (7%) achieved a partial response (PR) (total
      SD>6 months/PR= 14 (34%)). Of the 14 patients with SD>=6 months/PR, eight (57%)
      had received prior sequential bevacizumab and cetuximab, two (5%) had received
      bevacizumab and cetuximab concurrently, and four (29%) had received prior
      bevacizumab but not cetuximab or erlotinib (though three had received prior
      panitumumab). The combination of bevacizumab, cetuximab, and erlotinib was well
      tolerated and demonstrated antitumor activity in heavily pretreated patients with
      metastatic colorectal cancer. 

PMID- 25594064
TI  - The diverse lives of TRAP1.

PMID- 25594065
TI  - Menin-mediated regulation of miRNA biogenesis uncovers the IRS2 pathway as a
      target for regulating pancreatic beta cells.
AB  - Menin, a protein encoded by the MEN1 gene, is mutated in patients with multiple
      endocrine neoplasia type 1 (MEN1). Menin acts as a tumor suppressor in endocrine
      organs while it is also required for transformation of a subgroup of leukemia.
      The recently solved crystal structure of menin with different binding partners
      reveals that menin is a key scaffold protein that cross-talks with various
      partners, including transcription factors, to regulate gene transcription. Our
      recent findings unravel a previously undiscovered mechanism for menin-mediated
      control of gene expression via processing of certain microRNA's, thus adding to
      the plethora of ways in which menin regulates gene expression. By interacting
      with ARS2, an RNA binding protein, menin facilitates the processing of pri-let 7a
      and pri-miR155 to pre-let 7a and pre-miR155 respectively. Consistently, excision
      of the Men1 gene results in upregulation of IRS2, a let-7a target. As IRS2 is
      known to mediate both insulin signaling and insulin-induced cell proliferation,
      and let-7a targets include oncogenes like RAS and HMGA2, a deeper understanding
      of the menin-ARS2 complex in regulating miRNA biogenesis will yield further
      insights into the pathogenesis of the MEN1 syndrome and other menin-associated
      malignancies. 

PMID- 25594066
TI  - An old friend with new skills: Imiquimod as novel inhibitor of Hedgehog signaling
      in basal cell carcinoma.
AB  - Deregulated Hedgehog (HH)/GLI signaling plays an etiologic role in the
      initiation, progression and maintenance of many cancers. Small molecule targeting
      of HH signaling by inhibiting the essential pathway effector Smoothened (SMO) has
      proven exceptionally efficient for the treatment of advanced and metastatic basal
      cell carcinoma. That said, severe side effects, limited response rates, SMO
      independent GLI signaling and rapid development of drug resistance limit the
      therapeutic success of SMO antagonists, urgently calling for the identification
      of alternative and additional strategies repressing oncogenic HH signaling. In
      this perspective article we highlight recent findings showing that the Toll-like
      receptor-7/8 (TLR7/8) agonist imiquimod (IMQ), an immune modulator approved for
      the treatment of basal cell carcinoma, can also act as a potent cell autonomous
      inhibitor of oncogenic HH signaling. Surprisingly, IMQ reduces HH signal strength
      independent of TLR signaling, via adenosine receptor (ADORA)/Adenylate cyclase
      (AC)/Protein kinase A (PKA) activation. We here highlight the molecular
      mechanisms of IMQ-mediated repression of HH/GLI and discuss the possible benefits
      as well as challenges of using ADORA agonists for the treatment of HH-associated
      cancer. 

PMID- 25594067
TI  - Epigenetic and genetic dispositions of ovarian carcinomas.
AB  - Ovarian clear cell carcinoma has unique clinical characteristics with slow growth
      and a stress-resistant phenotype that is epigenetically induced during cancer
      progression in an inflammatory microenvironment. We refer to this as an
      epigenetic disposition, which is frequently associated with unique biomolecular
      features including prominent alterations in methylation, microsatellite
      instability and ARID1A mutations. This characteristic methylation profile also
      affects glucose metabolism, commonly known as the Warburg effect. In contrast,
      high-grade ovarian serous adenocarcinoma has a genetic disposition that is
      accompanied by rapid growth, TP53 mutations and chromosomal instability. The
      concept of epigenetic and genetic dispositions is applicable to various
      malignancies, including gastric and colorectal cancers. These disposition
      classifications are based on fundamental characteristics of malignancies and may
      provide a new vantage point for development of individualized therapies. 

PMID- 25594069
TI  - Targeting the oncogene B lymphoma deregulator IgH 3' regulatory region does not
      impede the in vivo inflammatory response in mice.
AB  - The IgH 3' regulatory region (3'RR), encompassing the four transcriptional
      enhancers hs3a-hs1,2-hs3b-hs4, is a potent lymphoma oncogene deregulator but its
      role in B cell-mediated inflammatory responses is unknown. We investigated the
      3'RR involvement in the in vivo pristane-induced inflammatory response in BALB/c
      mice. The lack of the 3'RR in BALB/c mice had no wide effect on the incidence,
      the kinetic of development and the cellular composition of peritoneal ascites.
      Ascite pro-inflammatory cytokines levels (IL-6, IL-21, IL-12/23, TNF-alpha) were
      unchanged while anti-inflammatory cytokines levels (IL-10, interferon-gamma) were
      slightly increased in 3'RR-deficient BALB/c mice as compared to wt BALB/c mice.
      In conclusion, the 3'RR is dispensable for the efficient recruitment of immune
      cells and the normal development of an inflammatory response in the in vivo
      pristane-induced inflammatory model. The 3'RR might be considered as a potential
      suitable target for anti-lymphoma pharmacological therapy without potent adverse
      effect on normal immune and inflammatory responses. 

PMID- 25594068
TI  - Just like the rest of evolution in Mother Nature, the evolution of cancers may be
      driven by natural selection, and not by haphazard mutations.
AB  - Sporadic carcinogenesis starts from immortalization of a differentiated somatic
      cell or an organ-specific stem cell. The immortalized cell incepts a new or
      quasinew organism that lives like a parasite in the patient and usually proceeds
      to progressive simplification, constantly engendering intermediate organisms that
      are simpler than normal cells. Like organismal evolution in Mother Nature, this
      cellular simplification is a process of Darwinian selection of those mutations
      with growth- or survival-advantages, from numerous ones that occur randomly and
      stochastically. Therefore, functional gain of growth- or survival-sustaining
      oncogenes and functional loss of differentiation-sustaining tumor suppressor
      genes, which are hallmarks of cancer cells and contribute to phenotypes of
      greater malignancy, are not drivers of carcinogenesis but are results from
      natural selection of advantageous mutations. Besides this mutation-load dependent
      survival mechanism that is evolutionarily low and of an asexual nature, cancer
      cells may also use cell fusion for survival, which is an evolutionarily-higher
      mechanism and is of a sexual nature. Assigning oncogenes or tumor suppressor
      genes or their mutants as drivers to induce cancer in animals may somewhat coerce
      them to create man-made oncogenic pathways that may not really be a course of
      sporadic cancer formations in the human. 

PMID- 25594070
TI  - In silico functional analyses and discovery of survival-associated microRNA
      signatures in pediatric osteosarcoma.
AB  - PURPOSE: Osteosarcoma is the most common bone tumor in children, adolescents, and
      young adults. In contrast to other childhood malignancies, no biomarkers have
      been consistently identified as predictors of outcome. This study was conducted
      to assess the microRNAs(miRs) expression signatures in pre-treatment osteosarcoma
      specimens and correlate with outcome to identify biomarkers for disease relapse.
      RESULTS: A 42-miRs signature whose expression levels were associated with overall
      and relapse-free survival waas identified. There were 8 common miRs between the
      two sets of survival-associated miRs. Bioinformatic analyses of these survival
      associated miRs suggested that they might regulate genes involved in ubiquitin
      proteasome system, TGFb, IGF, PTEN/AKT/mTOR, MAPK, PDGFR/RAF/MEK/ERK, and
      ErbB/HER pathways. METHODS: The cohort consisted of 27 patients of 70% Mexican
      American ethnicity. High-throughput RT-qPCR approach was used to generate
      quantitative expression of 754 miRs in the human genome. We examined tumor
      recurrence status, survival time and their association with miR expression levels
      by Cox proportional hazard regression analysis. TargetScan was used to predict
      miR/genes interactions, and functional analyses using KEGG, BioCarta, Gene
      Ontology were applied to these potential targets to predict deregulated pathways.
      CONCLUSIONS: Our findings suggested that these miRs might be potentially useful
      as prognostic biomarkers and therapeutic targets in pediatric osteosarcoma.

PMID- 25594071
TI  - Quantification of a New Anti-Cancer Molecule MJC13 Using a Rapid, Sensitive, and
      Reliable Liquid Chromatography-Tandem Mass Spectrometry Method.
AB  - MJC13 is a novel molecule that has potential use for the treatment of hormone
      refractory prostate cancer (HRPC). The purpose of this work was to develop a
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for
      quantification of MJC13. Itraconazole was used as the internal standard (IS).
      Acetonitrile was used to extract MJC13 from rat plasma and urine samples. A LC
      system equipped with a Waters XTerra MS C18 column (125A, 3.5 um, 4.6*150 mm) was
      used for chromatographic separation with acetonitrile-water as mobile phase. The
      API 3200 QTRAP triple quadrupole mass spectrometer was used for chromatographic
      analysis by multiple reaction monitoring (MRM) at positive mode with the
      transitions m/z 272->m/z 162 for MJC13, and m/z 705->m/z 392 for IS. The
      retention times for MJC13 and IS were 4.98 min and 4.42 min, respectively. The
      standard curves of MJC13 in solution, rat plasma, and rat urine were linear in
      the concentration range of 1 - 1000, 1 - 1000 and 1 - 200 ng/mL, respectively.
      The intra- and inter-day accuracy (relative error) ranged from 1.99 - 4.20% and
      1.83 - 4.39%, respectively. The intra- and inter-day precision (coefficient of
      variation) ranged from 2.27 - 3.88% and 2.80 - 4.79%, respectively. The
      extraction recovery rates of rat plasma and urine samples were 95.3% and 96.2%,
      respectively. No measurable matrix effect interfered with MJC13 identification
      and quantification in rat plasma and urine. In summary, a rapid, specific,
      sensitive, and reproducible LC-MS/MS method was developed and validated to
      quantify MJC13 in solution, rat plasma, and rat urine.

PMID- 25594072
TI  - A Novel Pathway that Links Caveolin-1 Down-Regulation to BRCA1 Dysfunction in
      Serous Epithelial Ovarian Cancer Cells.
AB  - Ovarian cancer is the second most common gynecological cancer and the five-year
      survival rate is only about 40%. High-grade serous carcinoma is the pre-dominant
      histotype associated with hereditary ovarian cancer and women with inherited
      mutations in BRCA1 have a lifetime risk of 40-60%. BRCA1 and its isoform BRCA1a
      are multifunctional proteins that are the most evolutionary conserved of all the
      other splice variants. Our group has previously reported that BRCA1/1a proteins,
      unlike K109R and C61G mutants, suppress growth of ovarian cancer cells by
      tethering Ubc9. In this study we found wild type BRCA1/1a proteins to induce
      expression of caveolin-1, a tumor suppressor in BRCA1-mutant serous epithelial
      ovarian cancer (SEOC) cells by immunofluorescence analysis. The K109R and C61G
      disease associated mutant BRCA1 proteins that do not bind Ubc9 were not as
      efficient in up-regulation of caveolin-1 expression in SEOC cells. Additionally,
      immunofluorescence analysis showed BRCA1/1a proteins to induce redistribution of
      Caveolin-1 from cytoplasm and nucleus to the cell membrane. This is the first
      study demonstrating the physiological link between loss of Ubc9 binding, loss of
      growth suppression and loss of Caveolin-1 induction of disease-associated mutant
      BRCA1 proteins in SEOC cells. Decreased Caveolin-1 expression combined with
      elevated Ubc9 expression can in the future be used as an early biomarker for
      BRCA1 mutant SEOC.

PMID- 25594075
TI  - Mapping to Irregular Torus Topologies and Other Techniques for Petascale
      Biomolecular Simulation.
AB  - Currently deployed petascale supercomputers typically use toroidal network
      topologies in three or more dimensions. While these networks perform well for
      topology-agnostic codes on a few thousand nodes, leadership machines with 20,000
      nodes require topology awareness to avoid network contention for communication
      intensive codes. Topology adaptation is complicated by irregular node allocation
      shapes and holes due to dedicated input/output nodes or hardware failure. In the
      context of the popular molecular dynamics program NAMD, we present methods for
      mapping a periodic 3-D grid of fixed-size spatial decomposition domains to 3-D
      Cray Gemini and 5-D IBM Blue Gene/Q toroidal networks to enable hundred-million
      atom full machine simulations, and to similarly partition node allocations into
      compact domains for smaller simulations using multiple-copy algorithms.
      Additional enabling techniques are discussed and performance is reported for NCSA
      Blue Waters, ORNL Titan, ANL Mira, TACC Stampede, and NERSC Edison.

PMID- 25594073
TI  - What do primary care prediabetes patients need? A baseline assessment of patients
      engaging in a technology-enhanced lifestyle intervention.
AB  - OBJECTIVE: This study assessed the baseline knowledge, perceptions, attitudes and
      behaviors of prediabetes patients in order to tailor a new technology-enhanced
      primary care-based lifestyle modification intervention. METHODS: Patients with a
      diagnosis of prediabetes were enrolled in a randomized, controlled pilot study,
      Avoiding Diabetes Thru Action Plan Targeting (ADAPT), a technology-based
      intervention to promote action plan discussions around patient-selected behavior
      change goals. RESULTS: A total of 54 adults (82% female) were enrolled in the
      pilot study. Most (89%) had comorbid conditions and mean BMI was 36. Participants
      exhibited high risk of diabetes knowledge (knowledge score 20 on a 32 point
      scale) and high levels of willingness to make changes to decrease diabetes risk.
      Number of daily steps was inversely correlated with perceived physical activity
      (r=-0.35082, p<0.001). Poorer scores on diet quality were inversely correlated
      with BMI. CONCLUSION: Participants in this sample demonstrated requisite levels
      of knowledge, self-efficacy, motivation and risk perception for effective
      behavior change. These data suggest that primary care-based prediabetes
      interventions can move beyond educational goals and focus on enhancing patients'
      ability to select, plan and enact action plans.

PMID- 25594076
TI  - Persistent Reeb Graph Matching for Fast Brain Search.
AB  - In this paper we propose a novel algorithm for the efficient search of the most
      similar brains from a large collection of MR imaging data. The key idea is to
      compactly represent and quantify the differences of cortical surfaces in terms of
      their intrinsic geometry by comparing the Reeb graphs constructed from their
      Laplace-Beltrami eigenfunctions. To overcome the topological noise in the Reeb
      graphs, we develop a progressive pruning and matching algorithm based on the
      persistence of critical points. Given the Reeb graphs of two cortical surfaces,
      our method can calculate their distance in less than 10 milliseconds on a PC. In
      experimental results, we apply our method on a large collection of 1326 brains
      for searching, clustering, and automated labeling to demonstrate its value for
      the "Big Data" science in human neuroimaging.

PMID- 25594074
TI  - Is Apolipoprotein E4 an Important Risk Factor for Dementia in Persons with Down
      Syndrome?
AB  - Down syndrome is one of the most common genetic causes of intellectual disability
      and is characterized by a number of behavioral as well as cognitive symptoms.
      Triplication of all or part of human chromosome 21 has been considered as the
      main cause of Down syndrome. Due to the location of the amyloid precursor protein
      on chromosome 21, many of the neuropathological features of early-onset
      Alzheimer's disease including senile plaques and neurofibrillary tangles are also
      present in Down syndrome patients who are either demented or nondemented.
      Significant advances in medical treatment have increased longevity in people with
      Down syndrome resulting in an increased population that may be subjected to many
      of the same risk factors as those with Alzheimer's disease. It is well
      established that harboring one or both apolipoprotein E4 alleles greatly
      increases the risk for Alzheimer's disease. However, whether apolipoprotein E4
      contributes to an earlier onset of dementia or increased mortality in Down
      syndrome patients is still a matter of debate. The purpose of this mini review is
      to provide an updated assessment on apolipoprotein E4 status and risk potential
      of developing dementia and mortality associated with Down syndrome.

PMID- 25594077
TI  - Infrared micro-spectroscopy for cyto-pathological classification of esophageal
      cells.
AB  - We report results from a study utilizing infrared spectral cytopathology (SCP) to
      detect abnormalities in exfoliated esophageal cells. SCP has been developed over
      the past decade as an ancillary tool to classical cytopathology. In SCP, the
      biochemical composition of individual cells is probed by collecting infrared
      absorption spectra from each individual, unstained cell, and correlating the
      observed spectral patterns, and the variations therein, against classical
      diagnostic methods to obtain an objective, machine-based classification of cells.
      In the past, SCP has been applied to the analysis and classification of cells
      exfoliated from the cervix and the oral cavity. In these studies, it was
      established that SCP can distinguish normal and abnormal cell types. Furthermore,
      SCP can differentiate between truly normal cells, and cells with normal
      morphology from the vicinity of abnormalities. Thus, SCP may be a valuable tool
      for the screening of early stages of dysplasia and pre-cancer. 

PMID- 25594078
TI  - Eumelanin-inspired core derived from vanillin: a new building block for organic
      semiconductors.
AB  - An eumelanin-inspired core derived from the natural product, vanillin (vanilla
      bean extract) was utilized for the synthesis of eumelanin-inspired small
      molecules and polymer via Sonogashira cross coupling. The materials demonstrate
      that the methyl 4,7-dibromo-5,6-dimethoxy-N-methyl-1H-indole-2-carboxylate core
      can serve as a new building block for organic semiconductors. 

PMID- 25594079
TI  - Photochemical synthesis of size-tailored hexagonal ZnS quantum dots.
AB  - ZnS quantum dots were synthetized at room temperature using a simple
      photochemical process involving ketyl radicals. Through the simple adjustment of
      reagent concentration, the method allows the control of nanoparticle size.
      Transmission electron microscopy confirmed that the nanomaterial adopts the
      hexagonal structure. 

PMID- 25594080
TI  - Carbon dot hybrids with oligomeric silsesquioxane: solid-state luminophores with
      high photoluminescence quantum yield and applicability in white light emitting
      devices.
AB  - We present a simple approach towards highly efficient solid-state luminophores
      with strong deep blue emission and a record high photoluminescence quantum yield
      of 60% by embedding water-soluble N,S-co-doped carbon dots into a polyhedral
      oligomeric silsesquioxane (POSS) matrix. 

PMID- 25594081
TI  - Single-base mismatch discrimination by T7 exonuclease with target cyclic
      amplification detection.
AB  - T7 exonuclease is reported for the first time to have high specificity in
      discriminating single-base mismatch and utilized for developing a target cyclic
      amplification biosensor strategy for sensitive SNP detection based on graphene
      oxide quenching of uncleaved probes. 

PMID- 25594082
TI  - Controlled growth of extended arrays of CoSi2 hexagonal nanoplatelets buried in
      Si(001), Si(011) and Si(111) wafers.
AB  - Because of their high electrical conductivity CoSi2 nanostructures are potential
      candidates for preparing ordered nano-arrays to be used as electrode
      interconnectors and contacts in microelectronic devices. We here describe a
      controlled procedure for the endotaxial growth of hexagonal CoSi2 nanoplatelets
      buried in differently oriented single crystalline Si wafers on which a Co-doped
      SiO2 thin film was previously deposited. These nanomaterials were obtained by a
      clean procedure consisting of isothermal annealing at 750  degrees C under a He
      atmosphere of Co-doped SiO2 thin films deposited onto the surface of three
      differently oriented flat Si substrates, namely Si(001), Si(011) and Si(111).
      Buried CoSi2 nanoplatelets are in all cases spontaneously formed as a consequence
      of the diffusion of Co atoms into the silicon wafer and their reaction with host
      Si atoms. Our TEM and GISAXS analyses demonstrated that these arrays,
      irrespective of host Si orientation, consist of CoSi2 hexagonal nanoplatelets in
      all cases parallel to Si{111} crystallographic planes. Additionally, the
      dimensions of the nanoplatelets were consistently determined by TEM and GISAXS
      for the three different host Si single crystal orientations. 

PMID- 25594083
TI  - Enhanced charge collection with ultrathin AlOx electron blocking layer for hole
      transporting material-free perovskite solar cell.
AB  - An ultrathin AlOx layer has been deposited onto a CH3NH3PbI3 film using atomic
      layer deposition technology, to construct a metal-insulator-semiconductor (MIS)
      back contact for the hole-transporting material-free perovskite solar cell. By
      optimization of the ALD deposition cycles, the average power conversion
      efficiency (PCE) of the cell has been enhanced from 8.61% to 10.07% with a
      highest PCE of 11.10%. It is revealed that the improvement in cell performance
      with this MIS back contact is mainly attributed to the enhancement in charge
      collection resulting from the electron blocking effect of the AlOx layer. 

PMID- 25594084
TI  - Self-assembly of SnO2 quantum dots into hierarchically ordered structures
      assisted by oriented attachment.
AB  - Taking SnO2 quantum dots with random orientation as a precursor, NaOH induces
      self-assembly of SnO2 dots to form the nanowires, side-by-side attachment of
      which generates hierarchically ordered structures. The multistep oriented
      attachment mechanism can help to describe the oriented assembly of big
      nanocrystals. 

PMID- 25594085
TI  - Image challenge: an unusual cause of a non-ST segment elevation myocardial
      infarction.

PMID- 25594086
TI  - [Keep the requirement for external review of the medical graduate education].

PMID- 25594087
TI  - [Medical ethics versus crude martial arts. Knockout MMA?].

PMID- 25594089
TI  - A genomic distance for assembly comparison based on compressed maximal exact
      matches.
AB  - Genome assemblies are typically compared with respect to their contiguity,
      coverage, and accuracy. We propose a genome-wide, alignment-free genomic distance
      based on compressed maximal exact matches and suggest adding it to the benchmark
      of commonly used assembly quality metrics. Maximal exact matches are perfect
      repeats, without gaps or misspellings, which cannot be further extended to either
      their left- or right-end side without loss of similarity. The genomic distance
      here proposed is based on the normalized compression distance, an information
      theoretic measure of the relative compressibility of two sequences estimated
      using multiple finite-context models. This measure exposes similarities between
      the sequences, as well as, the nesting structure underlying the assembly of
      larger maximal exact matches from smaller ones. We use four human genome
      assemblies for illustration and discuss the impact of genome sequencing and
      assembly in the final content of maximal exact matches and the genomic distance
      here proposed.

PMID- 25594088
TI  - [New guidelines for reducing the risk of sudden infant death. "Triple risk model"
      provide the basis for prevention].
AB  - The Swedish National Board of Health and Welfare has presented new advice to
      reduce the risk of Sudden Infant Death Syndrome, SIDS, supplemented with factual
      material for health personnel. The advice state: 1) The infant should sleep on
      its back, 2) parents should refrain from nicotine, 3) the infant's face should be
      kept free, overheating avoided and movements not restrained, 4) the safest place
      to sleep for an infant under three months is in its own cot, 5) breast-feed if
      possible, and 6) pacifier (dummy) can be used when the infant is going to sleep.
      Apparent life-threatening events in the maternity ward are discussed. In early
      breast-feeding attempts, it should be checked that breathing is free to avoid
      suffocation accidents. The best hypothesis of SIDS pathogenesis seems to be
      offered by the triple risk model, suggesting that an interaction of different
      risk factors leads to SIDS: 1) a critical developmental period, 2) a vulnerable
      infant and 3) an exogenous stressor (extrinsic risk factor).

PMID- 25594090
TI  - Obituary--Alexander Livingston.

PMID- 25594091
TI  - [Comment on "Fibrinolysis for patients with intermediate-risk pulmonary
      embolism"].

PMID- 25594092
TI  - Ethical dilemmas in the care of Afghan women by American military surgeons.

PMID- 25594093
TI  - Author response.

PMID- 25594094
TI  - In memory of Allan K. Roepstorff.

PMID- 25594095
TI  - [Vestibular function: migraine extends to the inner ear].

PMID- 25594097
TI  - Retraction notice to "Biomass supply chain optimisation for Organosolv-based
      biorefineries" [Bioresour. Technol. 159 (2014) 387-396].

PMID- 25594096
TI  - [Benign paroxysmal positional vertigo: frequent misdiagnosis].

PMID- 25594098
TI  - Early-infant diagnostic predictors of the neuro-behavioral  development after
      neonatal care.
AB  - Multidimensional diagnosis plays a central role in infant developmental care,
      which leads to the prediction of future disabilities. Information consolidated
      from objective and subjective, early and late, central and peripheral data may
      reveal neuro-pathological mechanisms and realize earlier and more precise
      preventive intervention. In the current study, we retrospectively searched
      correlating factors to the following neurological and behavioral development of
      'Head Control' and 'Roll Over' using multivariate correlation analysis of differ
      ent diagnostic domains over age, subject/object information of the patients who
      were previously admitted in our neonatal intensive care unit (NICU) and could be
      developmentally followed up in our outpatient clinic. Based on the hematologic
      and biochemical data, MRI brain anatomy during NICU hospitalization, we
      characterized all the acquired data distribution from 31 infants with either
      'appeared neurologically normal (ANN, n = 21)' or 'appeared neurologically
      abnormal (ANA, n = 10)' pro tempore, with a physician's clinical judgment before
      discharge. Besides single factor comparisons between ANN and ANA, we examined
      their development difference by using the multidimensional information
      processing, principal component analysis (PCA). The diagnostic predictors of
      neuro-behavioral development were selected by regression analysis with variable
      selection. It resulted that hematological and brain anatomical factors seemed
      correlated to both 'Head Control' and 'Roll Over'. This report suggested certain
      possibility of the cross-domain translational approach between subjective and
      objective developmental information through multivariate analyses, with candidate
      markers preliminarily to be evaluated in further studies.

PMID- 25594099
TI  - Hospitals struggle with supply costs as patient volume and acuity grow.

PMID- 25594100
TI  - Largest skilled-nursing providers.

PMID- 25594101
TI  - Cy3 photoprotection mediated by Ni2+ for extended single-molecule imaging: old
      tricks for new techniques.
AB  - The photostability of reporter fluorophores in single-molecule fluorescence
      imaging is of paramount importance, as it dictates the amount of relevant
      information that may be acquired before photobleaching occurs. Quenchers of
      triplet excited states are thus required to minimize blinking and sensitization
      of singlet oxygen. Through a combination of single-molecule studies and ensemble
      mechanistic studies including laser flash photolysis and time-resolved
      fluorescence, we demonstrate herein that Ni(2+) provides a much desired physical
      route (chemically inert) to quench the triplet excited state of Cy3, the most
      ubiquitous green emissive dye utilized in single-molecule studies. 

PMID- 25594102
TI  - Mode-selective control of the crystal lattice.
AB  - CONSPECTUS: Driving phase changes by selective optical excitation of specific
      vibrational modes in molecular and condensed phase systems has long been a grand
      goal for laser science. However, phase control has to date primarily been
      achieved by using coherent light fields generated by femtosecond pulsed lasers at
      near-infrared or visible wavelengths. This field is now being advanced by
      progress in generating intense femtosecond pulses in the mid-infrared, which can
      be tuned into resonance with infrared-active crystal lattice modes of a solid.
      Selective vibrational excitation is particularly interesting in complex oxides
      with strong electronic correlations, where even subtle modulations of the
      crystallographic structure can lead to colossal changes of the electronic and
      magnetic properties. In this Account, we summarize recent efforts to control the
      collective phase state in solids through mode-selective lattice excitation. The
      key aspect of the underlying physics is the nonlinear coupling of the resonantly
      driven phonon to other (Raman-active) modes due to lattice anharmonicities,
      theoretically discussed as ionic Raman scattering in the 1970s. Such nonlinear
      phononic excitation leads to rectification of a directly excited infrared-active
      mode and to a net displacement of the crystal along the coordinate of all
      anharmonically coupled modes. We present the theoretical basis and the
      experimental demonstration of this phenomenon, using femtosecond optical
      spectroscopy and ultrafast X-ray diffraction at a free electron laser. The
      observed nonlinear lattice dynamics is shown to drive electronic and magnetic
      phase transitions in many complex oxides, including insulator-metal transitions,
      charge/orbital order melting and magnetic switching in manganites. Furthermore,
      we show that the selective vibrational excitation can drive high-TC cuprates into
      a transient structure with enhanced superconductivity. The combination of
      nonlinear phononics with ultrafast crystallography at X-ray free electron lasers
      may provide new design rules for the development of materials that exhibit these
      exotic behaviors also at equilibrium.

PMID- 25594103
TI  - Regional material flow accounting and environmental pressures: the Spanish case.
AB  - This paper explores potential contributions of regional material flow accounting
      to the characterization of environmental pressures. With this aim, patterns of
      material extraction, trade, consumption, and productivity for the Spanish regions
      were studied within the 1996-2010 period. The main methodological variation as
      compared to whole-country based approaches is the inclusion of interregional
      trade, which can be separately assessed from the international exchanges. Each
      region was additionally profiled regarding its commercial exchanges with the rest
      of the regions and the rest of the world and the related environmental pressures.
      Given its magnitude, interregional trade is a significant source of environmental
      pressure. Most of the exchanges occur across regions and different extractive and
      trading patterns also arise at this scale. These differences are particularly
      great for construction minerals, which in Spain represent the largest share of
      extracted and consumed materials but do not cover long distances, so their impact
      is visible mainly at the regional level. During the housing bubble, economic
      growth did not improve material productivity. 

PMID- 25594104
TI  - Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC
      HRMS.
AB  - The concentrations of the neurotoxins, annonacin and squamocin, were determined
      in a lyophilized sample of the fruit pulp of the North American pawpaw (Asimina
      triloba) by LC coupled to high resolution mass spectrometry or LC-HRMS. The
      sample was extracted using dry methanol at 100  degrees C and 10 MPa pressure in
      a sealed container. The extraction of annonacin and squamocin was optimal at 100 
      degrees C with 7.72 and 0.162 mg/g, respectively, being found. Also, several
      isomers of annonacin and squamocin were separated and detected but not
      quantified.

PMID- 25594105
TI  - Whole-body CT-based imaging algorithm for multiple trauma patients: radiation
      dose and time to diagnosis.
AB  - OBJECTIVE: To determine the number of imaging examinations, radiation dose and
      the time to complete trauma-related imaging in multiple trauma patients before
      and after introduction of whole-body CT (WBCT) into early trauma care. METHODS:
      120 consecutive patients before and 120 patients after introduction of WBCT into
      the trauma algorithm of the University Hospital Zurich were compared regarding
      the number and type of CT, radiography, focused assessment with sonography for
      trauma (FAST), additional CT examinations (defined as CT of the same body regions
      after radiography and/or FAST) and the time to complete trauma-related imaging.
      RESULTS: In the WBCT cohort, significantly more patients underwent CT of the
      head, neck, chest and abdomen (p < 0.001) than in the non-WBCT cohort, whereas
      the number of radiographic examinations of the cervical spine, chest and pelvis
      and of FAST examinations were significantly lower (p < 0.001). There were no
      significant differences between cohorts regarding the number of radiographic
      examinations of the upper (p = 0.56) and lower extremities (p = 0.30). We found
      significantly higher effective doses in the WBCT (29.5 mSv) than in the non-WBCT
      cohort (15.9 mSv; p < 0.001), but fewer additional CT examinations for completing
      the work-up were needed in the WBCT cohort (p < 0.001). The time to complete
      trauma-related imaging was significantly shorter in the WBCT (12 min) than in the
      non-WBCT cohort (75 min; p < 0.001). CONCLUSION: Including WBCT in the initial
      work-up of trauma patients results in higher radiation doses, but fewer
      additional CT examinations are needed, and the time for completing trauma-related
      imaging is shorter. ADVANCES IN KNOWLEDGE: WBCT in trauma patients is associated
      with a high radiation dose of 29.5 mSv.

PMID- 25594106
TI  - Attention-deficit/hyperactivity disorder symptoms in adults with self-reported
      epilepsy: Results from a national epidemiologic survey of epilepsy.
AB  - OBJECTIVE: To assess symptoms of attention-deficit/hyperactivity disorder (ADHD)
      and their impact among adults with epilepsy from a large community-based survey.
      METHODS: Adults who self-reported epilepsy were sent a postal survey including
      the Adult ADHD Self-Report Scale version 6 (ASRS-6), Physicians Health
      Questionnaire (PHQ-9), Generalized Anxiety Disorder Assessment 7 (GAD-7), and
      questions about seizure frequency and number of antiepileptic drugs (AEDs) during
      the preceding 3 months. Individuals with ASRS-6 scores >14 were classified as
      ASRS+, and those with lower scores as ASRS-. Outcome measures included the
      Quality of Life in Epilepsy Inventory 10 (QOLIE-10), Quality of Life and
      Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Sheehan Disability
      Scale (SDS). The relationship of ADHD symptoms to quality of life outcomes was
      modeled hierarchically, with linear regression controlling for sociodemographic
      covariates, comorbid depression and anxiety, seizure frequency, and number of
      AEDs. RESULTS: Among 1,361 of respondents with active epilepsy, 18.4% (n = 251)
      were classified as ASRS+ and at risk for ADHD. Compared to ASRS- cases, ASRS+
      individuals were more likely to have elevated depression and anxiety scores as
      well as greater seizure frequency and more AED use (p < 0.05 for all). Modeling
      results comparing ASRS+ and ASRS- cases, controlling for all covariates,
      indicated that ASRS+ cases had lower quality of life (Beta [beta] = -3.07, 95%
      confidence interval [CI] -4.19 to -1.96) and worse physical (beta = -0.048 95% CI
      -0.076 to -0.020) and social functioning (beta = -0.058, 95% CI -0.081 to -0.035)
      on the Q-LES-Q, and increases in family (beta = 1.57, 95% CI 1.09-2.05), social
      (beta = 1.68, 95% CI 1.20-2.16), and work-related disability (beta-1.86, 95% CI
      1.27-2.46). SIGNIFICANCE: ADHD symptoms occur in nearly one of five adults with
      epilepsy, and are associated with increased psychosocial morbidity and lowered
      QOL. Future studies should clarify the nature and causes of ADHD symptoms in
      adults with epilepsy.

PMID- 25594107
TI  - Directed self-assembly of silicon-containing block copolymer thin films.
AB  - The directed self-assembly (DSA) of lamella-forming poly(styrene-block
      trimethylsilylstyrene) (PS-PTMSS, L0=22 nm) was achieved using a combination of
      tailored top interfaces and lithographically defined patterned substrates. Chemo-
      and grapho-epitaxy, using hydrogen silsesquioxane (HSQ) based prepatterns,
      achieved density multiplications up to 6* and trench space subdivisions up to 7*,
      respectively. These results establish the compatibility of DSA techniques with a
      high etch contrast, Si-containing BCP that requires a top coat neutral layer to
      enable orientation.

PMID- 25594108
TI  - The methodological quality assessment tools for preclinical and clinical studies,
      systematic review and meta-analysis, and clinical practice guideline: a
      systematic review.
AB  - OBJECTIVE: To systematically review the methodological assessment tools for pre
      clinical and clinical studies, systematic review and meta-analysis, and clinical
      practice guideline. METHODS: We searched PubMed, the Cochrane Handbook for
      Systematic Reviews of Interventions, Joanna Briggs Institute (JBI) Reviewers
      Manual, Centre for Reviews and Dissemination, Critical Appraisal Skills Programme
      (CASP), Scottish Intercollegiate Guidelines Network (SIGN), and the National
      Institute for Clinical Excellence (NICE) up to May 20th, 2014. Two authors
      selected studies and extracted data; quantitative analysis was performed to
      summarize the characteristics of included tools. RESULTS: We included a total of
      21 assessment tools for analysis. A number of tools were developed by academic
      organizations, and some were developed by only a small group of researchers. The
      JBI developed the highest number of methodological assessment tools, with CASP
      coming second. Tools for assessing the methodological quality of randomized
      controlled studies were most abundant. The Cochrane Collaboration's tool for
      assessing risk of bias is the best available tool for assessing RCTs. For cohort
      and case-control studies, we recommend the use of the Newcastle-Ottawa Scale. The
      Methodological Index for Non-Randomized Studies (MINORS) is an excellent tool for
      assessing non-randomized interventional studies, and the Agency for Healthcare
      Research and Quality (ARHQ) methodology checklist is applicable for cross
      sectional studies. For diagnostic accuracy test studies, the Quality Assessment
      of Diagnostic Accuracy Studies-2 (QUADAS-2) tool is recommended; the SYstematic
      Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool is
      available for assessing animal studies; Assessment of Multiple Systematic Reviews
      (AMSTAR) is a measurement tool for systematic reviews/meta-analyses; an 18-item
      tool has been developed for appraising case series studies, and the Appraisal of
      Guidelines, Research and Evaluation (AGREE)-II instrument is widely used to
      evaluate clinical practice guidelines. CONCLUSIONS: We have successfully
      identified a variety of methodological assessment tools for different types of
      study design. However, further efforts in the development of critical appraisal
      tools are warranted since there is currently a lack of such tools for other
      fields, e.g. genetic studies, and some existing tools (nested case-control
      studies and case reports, for example) are in need of updating to be in line with
      current research practice and rigor. In addition, it is very important that all
      critical appraisal tools remain subjective and performance bias is effectively
      avoided.

PMID- 25594109
TI  - Fully printable mesoscopic perovskite solar cells with organic silane self
      assembled monolayer.
AB  - By the introduction of an organic silane self-assembled monolayer, an interface
      engineering approach is demonstrated for hole-conductor-free, fully printable
      mesoscopic perovskite solar cells based on a carbon counter electrode. The self
      assembled silane monolayer is incorporated between the TiO2 and CH3NH3PbI3,
      resulting in optimized interface band alignments and enhanced charge lifetime.
      The average power conversion efficiency is improved from 9.6% to 11.7%, with a
      highest efficiency of 12.7%, for this low-cost perovskite solar cell. 

PMID- 25594110
TI  - Depression and Substance Use: A Temporal-Ordered Model.
AB  - BACKGROUND AND OBJECTIVES: This study sought empirical evidence for the self
      medication hypothesis. It asked whether diagnosis of depression, together with
      the use of mental-health care, leads to substance use. METHODS: Data came from
      the 5-wave, longitudinal Fragile Families and Child Wellbeing (FFCW) Study, an
      investigation of a cohort of nearly 5,000 births, which over sampled non-marital
      births. FFCW examined newborns' biological mothers and fathers, all of whom lived
      in the United States. The adults were initially interviewed between 1998 and 2000
      (the period of the cohort's births); they were then re-interviewed for four times
      over 10 years. FFCW measured mental health-related variables, level of drug use,
      and social structural and demographic factors, all of which are also measured by
      the present study. Respondents in our study's two final subsamples had responded
      to every FFCW interview item we would use in constructing our final model's
      variables. Our subsample of mothers totaled 3,477 women, from whom 5,987 person
      waves were derived. Our subsample of fathers totaled 2,096 men, yielding 3,543
      person-waves. RESULTS: We used STATA generalized estimating equations for panel
      data, and found some evidence to support the self-medication hypothesis. In
      addition, our results indicated that the relationship of substance use to the use
      of mental-health care was gender-specific. Conclusions/Importance: Empirical
      evidence from this study only partially supported the self-medication hypothesis;
      the co-occurrence of depression and substance abuse in our sample was also
      reflective of social structural and demographic variables and of prior substance
      use variables.

PMID- 25594112
TI  - Cu-catalyzed aerobic oxidative three-component coupling route to N-sulfonyl
      amidines via an ynamine intermediate.
AB  - Cu-catalyzed aerobic oxidative three-component coupling of a terminal alkyne,
      secondary amine, and sulfonamide enables efficient synthesis of amidines. The use
      of Cu(OTf)2 (5 mol %) produces amidines selectively without Glaser-Hay alkyne
      homocoupling products. Preliminary studies suggest that the reaction pathway
      involves initial oxidative coupling of the terminal alkyne with the secondary
      amine, followed by hydroamidation of the ynamine intermediate with the
      sulfonamide. 

PMID- 25594111
TI  - Factors associated with the effect of interferon-alpha sequential therapy in
      order to discontinue nucleoside/nucleotide analog treatment in patients with
      chronic hepatitis B.
AB  - AIM: The factors associated with the outcome of sequential therapy with
      interferon-alpha (IFN-alpha) in order to halt nucleoside/nucleotide analog (NUC)
      maintenance treatment for chronic hepatitis B were analyzed. METHODS: A total of
      50 patients with chronic hepatitis B who underwent IFN-alpha sequential therapy
      for cessation of NUC were enrolled retrospectively. The subjects received NUC
      plus IFN-alpha for 4 weeks followed by IFN-alpha alone for 20 weeks. Natural IFN
      alpha of 6-MU doses was administrated three times a week. A successful response
      to NUC/IFN-alpha sequential therapy was defined as serum hepatitis B virus (HBV)
      DNA below 4.0 log copies/mL, serum alanine aminotransferase (ALT) below 30 IU/L,
      and hepatitis B e-antigen negativity at 24 months after completing the treatment.
      RESULTS: Multivariate analysis revealed that hepatitis B surface antigen (HBsAg)
      of 3.0 log U/mL or more (P < 0.002) and hepatitis B core-related antigen
      (hepatitis B core-related antigen [HBcrAg]) of 4.5 log U/mL or more (P < 0.003)
      at the start of IFN-alpha administration were significant factors associated with
      a 24-month non-response. Maximal levels of ALT and HBV DNA during the follow-up
      period after completing IFN-alpha therapy were significantly related (P < 0.001),
      and receiver operating characteristic analysis showed that both maximal ALT (P <
      0.001) and HBV DNA (P < 0.001) were significantly related to the final 24-month
      response. CONCLUSION: The combinational use of HBsAg and HBcrAg levels may be
      useful to predict the 24-month outcome of NUC/IFN-alpha sequential therapy.
      Maximal levels of ALT and HBV DNA during post-treatment follow-up may also help
      monitor responses to IFN-alpha sequential therapy.

PMID- 25594113
TI  - Promoting weight loss in asthma.

PMID- 25594115
TI  - Expression and functionality of Toll-like receptor 3 in the megakaryocytic
      lineage.
AB  - BACKGROUND: In addition to their key role in hemostasis, platelets and
      megakaryocytes regulate immune and inflammatory responses, in part through their
      expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA
      associated with viral infection. Thrombocytopenia is a frequent complication of
      viral infection. However, the expression and functionality of TLR3 in
      megakaryocytes and platelets is not yet well understood. OBJECTIVE: To study the
      expression and functionality of TLR3 in the megakaryocytic lineage. METHODS AND
      RESULTS: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3
      is expressed in CD34(+) cells, megakaryocytes, and platelets. Immunoblotting
      assays showed that stimulation of megakaryocytes with two synthetic agonists of
      TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-kappaB (NF-kappaB),
      phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase
      (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced
      platelet production in vitro and interferon-beta release through the PI3K-Akt and
      NF-kappaB signaling pathways. TLR3 ligands potentiated the aggregation mediated
      by classic platelet agonists. This effect was also observed for ATP release, but
      not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation
      was not involved in alpha-granule release. In addition, TLR3 agonists induced
      activation of the NF-kappaB, PI3K-Akt and ERK1/2 pathways in platelets.
      Reductions in platelet production and platelet fibrinogen binding mediated by
      Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3
      dsRNA complex. CONCLUSIONS: Our findings indicate that functional TLR3 is
      expressed in CD34(+) cells, megakaryocytes, and platelets, and suggest a
      potential role for this receptor in the megakaryopoiesis/thrombopoiesis
      alterations that occur in viral infections.

PMID- 25594117
TI  - Indoor air quality in green buildings: A case-study in a residential high-rise
      building in the northeastern United States.
AB  - Improved indoor air quality (IAQ) is one of the critical components of green
      building design. Green building tax credit (e.g., New York State Green Building
      Tax Credit (GBTC)) and certification programs (e.g., Leadership in Energy &
      Environmental Design (LEED)) require indoor air quality measures and compliance
      with allowable maximum concentrations of common indoor air pollutants. It is not
      yet entirely clear whether compliance with these programs results in improved IAQ
      and ultimately human health. As a case in point, annual indoor air quality
      measurements were conducted in a residential green high-rise building for five
      consecutive years by an industrial hygiene contractor to comply with the
      building's GBTC requirements. The implementation of green design measures
      resulted in better IAQ compared to data in references of conventional homes for
      some parameters, but could not be confirmed for others. Relative humidity and
      carbon dioxide were satisfactory according to existing standards. Formaldehyde
      levels during four out of five years were below the most recent proposed exposure
      limits found in the literature. To some degree, particulate matter (PM) levels
      were lower than that in studies from conventional residential buildings.
      Concentrations of Volatile Organic Compounds (VOCs) with known permissible
      exposure limits were below levels known to cause chronic health effects, but
      their concentrations were inconclusive regarding cancer health effects due to
      relatively high detection limits. Although measured indoor air parameters met all
      IAQ maximum allowable concentrations in GBTC and applicable LEED requirements at
      the time of sampling, we argue that these measurements were not sufficient to
      assess IAQ comprehensively because more sensitive sampling/analytical methods for
      PM and VOCs are needed; in addition, there is a need for a formal process to
      ensure rigor and adequacy of sampling and analysis methods. Also, we suggest that
      a comprehensive IAQ assessment should include mixed mode thermal comfort models,
      semi-volatile organic compounds, assessment of new chemicals, and permissible
      exposure levels of many known indoor VOCs and bioaerosols. Plus, the relationship
      between energy consumption and IAQ, and tenant education on health effects of
      indoor pollutants and their sources may need more attention in IAQ investigations
      in green buildings. 

PMID- 25594114
TI  - Tuning the reactivity of Fe(V)(O) toward C-H bonds at room temperature: effect of
      water.
AB  - The presence of an Fe(V)(O) species has been postulated as the active
      intermediate for the oxidation of both C-H and C?C bonds in the Rieske
      dioxygenase family of enzymes. Understanding the reactivity of these high valent
      iron-oxo intermediates, especially in an aqueous medium, would provide a better
      understanding of these enzymatic reaction mechanisms. The formation of an
      Fe(V)(O) complex at room temperature in an aqueous CH3CN mixture that contains up
      to 90% water using NaOCl as the oxidant is reported here. The stability of
      Fe(V)(O) decreases with increasing water concentration. We show that the
      reactivity of Fe(V)(O) toward the oxidation of C-H bonds, such as those in
      toluene, can be tuned by varying the amount of water in the H2O/CH3CN mixture.
      Rate acceleration of up to 60 times is observed for the oxidation of toluene upon
      increasing the water concentration. The role of water in accelerating the rate of
      the reaction has been studied using kinetic measurements, isotope labeling
      experiments, and density functional theory (DFT) calculations. A kinetic isotope
      effect of ~13 was observed for the oxidation of toluene and d8-toluene showing
      that C-H abstraction was involved in the rate-determining step. Activation
      parameters determined for toluene oxidation in H2O/CH3CN mixtures on the basis of
      Eyring plots for the rate constants show a gain in enthalpy with a concomitant
      loss in entropy. This points to the formation of a more-ordered transition state
      involving water molecules. To further understand the role of water, we performed
      a careful DFT study, concentrating mostly on the rate-determining hydrogen
      abstraction step. The DFT-optimized structure of the starting Fe(V)(O) and the
      transition state indicates that the rate enhancement is due to the transition
      state's favored stabilization over the reactant due to enhanced hydrogen bonding
      with water. 

PMID- 25594118
TI  - Preliminary evidence of the association between monochlorinated bisphenol A
      exposure and type II diabetes mellitus: A pilot study.
AB  - Evidence for the association of bisphenol A (BPA) with type II diabetes mellitus
      (T2DM) has been inconsistent in human studies. In-vitro and animal studies
      indicate that chlorinated BPA derivatives aggravate BPA health effects via higher
      estrogenic activity and alteration of membrane-initiating signaling pathways. We
      evaluated the association between urinary monochlorinated BPA (mono-ClBPA)
      concentrations and the incidence of T2DM. In our cross-sectional study, we
      identified 20 adult participants (>=18 yr) who reported having T2DM (doctor
      diagnosed) and 131 adults with normal health. First morning void urine samples
      were analyzed for total BPA and mono-ClBPA. Detection limits of the analytical
      method were 95 ng L(-1) for BPA and 32 ng L(-1) for mono-ClBPA. Multivariable
      logistic regression analyses and additive Bayesian network modeling were
      performed. After adjusting for age, gender, BMI, urinary total BPA and other
      confounders, the odds of having T2DM was 3.29 times higher (95% confidence
      interval, CI: 1.10, 11.4; P < 0.05) per unit increase in log-transformed and
      creatinine-adjusted urinary mono-ClBPA levels (n = 151); this relation did not
      hold for total BPA. The globally optimum Bayesian model corroborated the results
      of the logistic regression by expressing mono-ClBPA in the pathway of T2DM, and
      not for total BPA. An age-matched sensitivity analysis confirmed the increase in
      OR of T2DM by 3.04 times (95% CI: 1.10, 11.0; P < 0.05) per unit increase in log
      transformed and creatinine-adjusted urinary mono-ClBPA concentration (n = 68).
      The urinary monochlorinated BPA derivative was significantly associated with
      T2DM, whereas the parent compound (total BPA) was not. Caution should be applied
      in interpreting these findings, as this is the first study to report this
      association and the sample size of participants with T2DM is small. Additional
      research with a larger sample size coupled with relevant toxicological studies is
      warranted.

PMID- 25594116
TI  - Health care resource use and costs of two-year survivors of acute lung injury. An
      observational cohort study.
AB  - RATIONALE: Survivors of acute lung injury (ALI) require ongoing health care
      resources after hospital discharge. The extent of such resource use, and
      associated costs, are not fully understood. OBJECTIVES: For patients surviving at
      least 2 years after ALI, we evaluated cumulative 2-year inpatient admissions and
      related costs, and the association of patient- and intensive care unit-related
      exposures with these costs. METHODS: Multisite observational cohort study in 13
      intensive care units at four academic teaching hospitals evaluating 138 two-year
      survivors of ALI. MEASUREMENTS AND MAIN RESULTS: Two-year inpatient health care
      use data (i.e., admissions to hospitals, and skilled nursing and rehabilitation
      facilities) were collected for patients surviving at least 2 years, via (1) one
      time retrospective structured interview with patient and/or proxy, (2) systematic
      medical record review for nonfederal study site hospitals, and (3) inpatient
      medical record review for non-study site hospitals, as needed for clarifying
      patient/proxy reports. Costs are reported in 2013 U.S. dollars. A total of 138 of
      142 (97%) 2-year survivors completed the interview, with 111 (80%) reporting at
      least one inpatient admission during follow-up, for median (interquartile range
      [IQR]) estimated costs of $35,259 ($10,565-$81,166). Hospital readmissions
      accounted for 76% of costs. Among 12 patient- and intensive care unit-related
      exposures evaluated, baseline comorbidity and intensive care unit length of stay
      were associated with increased odds of incurring any follow-up inpatient costs.
      Having Medicare or Medicaid (vs. private insurance) was associated with median
      estimated costs that were 85% higher (relative median, 1.85; 95% confidence
      interval, 1.01-3.45; P=0.045). CONCLUSIONS: In this multisite study of 138 two
      year survivors of ALI, 80% had one or more inpatient admission, representing a
      median (IQR) estimated cost $35,259 ($10,565-$81,166) per patient and $6,598,766
      for the entire cohort. Hospital readmissions represented 76% of total inpatient
      costs, and having Medicare or Medicaid before ALI was associated with increased
      costs. With the aging population and increasing comorbidity, these findings have
      important health policy implications for the care of critically ill patients.

PMID- 25594120
TI  - Impact of an estrogenic sewage treatment plant effluent on life-history traits of
      the freshwater amphipod Gammarus pulex.
AB  - Despite efforts to upgrade sewage treatment plants (STPs) in the last decades,
      STPs are still a major source for the contamination of surface waters, including
      emerging pollutants such as pesticides, pharmaceuticals, personal care products
      and endocrine disrupting chemicals (EDCs). Because many of these substances are
      not completely removed in conventional STPs they are regularly detected in
      surface waters where they have the potential to affect local macroinvertebrate
      communities. The objective of the current work was to investigate the impact of
      an estrogenic wastewater effluent on the key life-history traits of the
      freshwater amphipod Gammarus pulex. G. pulex was exposed in artificial indoor
      flow-channels under constant conditions to different wastewater concentrations
      (0%, 33%, 66%, 100%). In parallel the estrogenic activity of wastewater samples
      was determined using the yeast estrogen screen (YES). Estrogenic activities in
      the STP effluent were up to 38.6 ng/L estradiol equivalents (EEQ). Amphipods
      exhibited an increasing body length with increasing wastewater concentrations.
      Furthermore, we observed a shift of the sex ratio in favour of females, a
      significantly increased fraction of brooding females and increased fecundity
      indices with increasing wastewater concentrations. The increased body length is
      likely to be attributed to the additional nutrient supply while the occurrence of
      EDCs in the wastewater is the probable cause for the altered sex ratio and
      fecundity in exposed Gammarus cohorts.

PMID- 25594119
TI  - Human exposure to airborne aldehydes in Chinese medicine clinics during
      moxibustion therapy and its impact on risks to health.
AB  - Many air toxicants, and especially aldehydes, are generated by moxibustion, which
      means burning Artemisia argyi. Our goal was to investigate indoor-air aldehyde
      emissions in Chinese medicine clinics (CMCs) during moxibustion to further
      evaluate the potential health risks, including cancer risk and non-cancer risk,
      to the medical staff and adult patients. First, the indoor-air-quality in 60
      public sites, including 15 CMCs, was investigated. Four CMCs with frequent use of
      moxibustion were selected from the 15 CMCs to gather the indoor airborne
      aldehydes in the waiting and therapy rooms. The mean values of formaldehyde and
      acetaldehyde in the CMCs' indoor air were 654 and 4230 MUg m(-3), respectively,
      in the therapy rooms, and 155 and 850 MUg m(-3), respectively, in the waiting
      rooms. The average lifetime cancer risks (Rs) and non-cancer risks (hazard
      quotients: HQs) of airborne formaldehyde and acetaldehyde among the CMC medical
      staff exceeded the acceptable criteria (R < 1.00 * 10(-3) and HQ < 1.00) for
      occupational workers. The patients' Rs and HQs were also slightly higher than the
      critical values (R = 1.00 * 10(-6) and HQ = 1.00). Our results indicate that
      airborne aldehydes pose a significant threat to the health of medical staff, and
      slightly affected the patients' health, during moxibustion in the CMCs.

PMID- 25594121
TI  - Retardation of iron-cyanide complexes in the soil of a former manufactured gas
      plant site.
AB  - The soil in the vicinities of former Manufactured Gas Plant (MGP) sites is
      commonly contaminated with iron-cyanide complexes (ferric ferrocyanide). The
      phenomenon of cyanide mobility in soil, according to the literature, is mainly
      governed by the dissolution and precipitation of ferric ferrocyanide, which is
      only slightly soluble (<1 mg L(-1)) under acidic conditions. In this paper,
      retention properties of the sandy loam soil and the potential vertical movement
      of the solid iron-cyanide complexes, co-existing with the dissolution, sorption
      and precipitation reactions were investigated. Preliminary research conducted on
      a former MGP site implied colloidal transport of ferric ferricyanide from the
      initial deposition in the wastes layer towards the sandy loam material (secondary
      accumulation), which possibly retarded the mobility of cyanide (CN). A series of
      batch and column experiments were applied in order to investigate the retardation
      of iron-cyanide complexes by the sandy loam soil. Batch experiments revealed that
      in circumneutral pH conditions sandy loam material decreases the potassium ferro-
      and ferricyanide concentration. In column experiments a minor reduction in CN
      concentration was observed prior to addition of iron sulfide (FeS) layer, which
      induced the formation of the Prussian blue colloids in circumneutral pH
      conditions. Precipitated solid iron-cyanide complexes were mechanically filtered
      by the coherent structure of the investigated soil. Additionally, the reduction
      of the CN concentration of the percolation solutions by the sandy loam soil was
      presumably induced due to the formation of potassium manganese iron-cyanide
      (K2Mn[Fe(CN)6]).

PMID- 25594122
TI  - Photolytic degradation of sulfamethoxazole and trimethoprim using UV-A, UV-C and
      vacuum-UV (VUV).
AB  - The photolytic degradation of the non-degradable pharmaceuticals sulfamethoxazole
      (SMX) and trimethoprim (TMP) in an aqueous solution was investigated using three
      kinds of low-pressure mercury lamp UV-A (352 nm), UV-C (254 nm), and vacuum-UV
      (VUV, 185 nm and 254 nm). The degradation rates were highly dependent on the
      target compounds as well as the UV sources. No degradation of the target
      compounds was observed using UV-A treatment, because there was no overlap between
      the UV-A emission spectrum and absorption spectrum of the target compounds. On
      the other hand, UVC and VUV revealed higher reactivity. The results also
      indicated that SMX had a greater potential to react photochemically than TMP.
      Among the UV sources, VUV was the most effective process for the degradation of
      target compounds. Furthermore, the addition of oxidants such as hydrogen peroxide
      (H2O2) and sodium persulfate (Na2S2O8) to the reaction system improved the
      overall degradation rate significantly.The experimental results for the VUV
      irradiated samples with the addition of methanol as a hydroxyl radical scavenger
      revealed that hydroxyl radicals contribute significantly to the elimination of
      the target compound. Overall, the degradation rate of the target compounds was in
      the order: VUV = UV-C > UV-A for sulfamethoxazole and VUV/H2O2 > VUV/ Na2S2O8 >
      VUV >UV-C >UV-A for trimethoprim.

PMID- 25594123
TI  - Multivariate optimization for electrochemical oxidation of methyl orange: Pathway
      identification and toxicity analysis.
AB  - Electrochemical oxidation of methyl orange (Sodium 4-[(4-dimethylamino)
      phenyldiazenyl] benzenesulfonate) with lead dioxide coated on mild steel was
      modelled using response surface methodology (RSM) to analyze the influence of pH,
      NaCl dose and current on color and chemical oxygen demand (COD) removal. Higher
      current, acidic pH and 0.8-1.2 g L(-1) NaCl dose had an enhancing effect on the
      removal efficiencies. Interaction effect of the variables highlights the action
      of (*)OH and HOCl in the oxidation of methyl orange, where HOCl has effect at
      lower current range. More than 90% COD removal efficiency and ~100% color removal
      efficiency was obtained in 5 h at optimum conditions for an initial concentration
      of 50 mg L(-1). High performance liquid chromatography-mass spectroscopy (HPLC
      MS) analysis carried out to identify degradation intermediates revealed the
      absence of chlorinated intermediates, which was further verified with Fourier
      transform infrared spectroscopy (FTIR) analysis. The postulated pathway of
      degradation indicated breakdown through dealkylation, deamination, desulfonation
      and cleavage of an azo bond and benzene ring. The degradation of methyl orange to
      smaller compounds was also confirmed by Ion Chromatography (IC). Cytotoxicity
      analysis on HaCaT cells revealed the intermediates to be more cytotoxic than the
      dye, possibly due to the aromatic amines and diazines formed during the
      degradation process.

PMID- 25594124
TI  - Concentration of Cryptosporidium oocysts from river water by coagulation and foam
      separation combined with acid dissolution of ferric flocs.
AB  - Cryptosporidium is an extremely virulent microorganism; contamination of water
      works systems by Cryptosporidium oocysts is a serious issue in public health.
      However, a great deal of effort is required to detect oocysts in source water for
      drinking, because the oocysts have to be concentrated from a large volume of
      water before detection. In this study, the concentration of oocysts in oocyst
      polluted artificial river water was examined by coagulation and foam separation.
      The oocysts concentrated in the foam water were purified using immunomagnetic
      separation and assessed using epifluorescence microscopy. When ferric coagulation
      was performed prior to foam separation, oocysts were effectively removed from the
      river water and concentrated in the foam within 10 min. The removal efficiency
      was greater than 96% at the optimum iron and casein concentrations of 5 mg-Fe L(
      1) and 20 mg L(-1), respectively. Furthermore, the number of recovered oocysts in
      the solution obtained by the dissolution of the collected ferric flocs from foam
      water was the same as that obtained using the Japanese standard procedure for
      detection of Cryptosporidium in water using membrane filtration. This is a novel
      method of concentrating Cryptosporidium oocysts for detection in river water
      using a coagulation and foam separation combined with acid dissolution of ferric
      flocs; the method is easy to use, rapid, and efficient.

PMID- 25594125
TI  - Sensitivity analyses and simulations of a full-scale experimental membrane
      bioreactor system using the activated sludge model No. 3 (ASM3).
AB  - An ASM3-based model was implemented in the numerical software MATHEMATICA where
      sensitivity analyses and simulations of a membrane bioreactor (MBR) system were
      carried out. These results were compared with those obtained using the commercial
      simulator WEST. Predicted values did not show significant variations between both
      software and simulations showed that the most influential operational conditions
      were influent flow rate and concentrations and bioreactor volumes. On the other
      hand, sensitivity analyses were carried out with both software programs for the
      same five outputs: COD, ammonium and nitrate concentrations in the effluent,
      total suspended solids concentration and oxygen uptake rate in the aerobic
      bioreactor. Similar results were in general obtained in both cases and according
      to these analyses, the most significant inputs over the model predictions were
      growth and storage heterotrophic biomass yields and decay coefficient. Other
      parameters related to the hydrolysis process or to the autotrophic biomass also
      significantly influenced model outputs. 

PMID- 25594126
TI  - Modelling wastewater treatment in a submerged anaerobic membrane bioreactor.
AB  - Mathematical modelling has been widely applied to membrane bioreactor (MBRs)
      processes. However, to date, very few studies have reported on the application of
      the anaerobic digestion model N.1 (ADM1) to anaerobic membrane processes. The aim
      of this study was to evaluate the applicability of the ADM1 to a submerged
      anaerobic MBR (SAMBR) treating simulated industrial wastewater composed of cheese
      whey and sucrose. This study demonstrated that the biological processes involved
      in SAMBRs can be modelled by using the ADM1. Moreover, the results showed that
      very few modifications of the parameters describing the ADM1 were required to
      reasonably fit the experimental data. In particular, adaptation to the specific
      conditions of the coefficients describing the wastewater characterisation and the
      reduction of the hydrolysis rate of particulate carbohydrate (khyd,ch) from 0.25
      d(-1) (as suggested by the ADM1 for high-rate mesophilic reactors) to 0.13 d(-1)
      were required to fit the experimental data. 

PMID- 25594127
TI  - Evaluation of hydraulic characteristics of a pilot-scale air-lift internal-loop
      bioreactor.
AB  - Using sodium fluoride as tracer, residence time distribution technique was
      employed to evaluate the hydraulic characteristics of a pilot-scale Internal-Loop
      Airlift Bio-particle (ILAB) bioreactor that was a novel system for ammonia
      removal from wastewater. The results showed that the flow pattern of ILAB reactor
      was close to completely mixed reactor under all the tested air flow rates and
      liquid flow rates (with average N of 1.88). The total dead zone (TDZ) was 32.43%
      with biological dead zone (BDZ) of 20.66% and hydraulic dead zone (HDZ) of 8.95%.
      At higher air flow rates, the flow pattern of reactor approached that of
      completely mixed reactor (N from 2.72 to 1.54), and the increase of air flow rate
      gave rise to the decrease of TDZ in the reactor (from 36.24% to 23.00%). Whereas
      at higher liquid flow rates, the flow pattern of ILAB reactor got away from that
      of completely mixed reactor (N from 1.51 to 1.72), and the increase of liquid
      flow rate yielded a rise of TDZ in the reactor (from 28.48% to 36.84%). The study
      highlighted that the effect of air flow rate on flow pattern and TDZ of the
      reactor was greater than that of liquid flow rate. 

PMID- 25594129
TI  - A randomized controlled study for the treatment of acne vulgaris using high
      intensity 414 nm solid state diode arrays.
AB  - The treatment of acne vulgaris poses a challenge to the dermatologist, and the
      disease causes emotional anxiety for the patient. The treatment of acne vulgaris
      may be well-suited to home-use applications, where sufferers may be too
      embarrassed to seek medical treatment. This randomized controlled study is
      designed to quantify the effectiveness of using a blue light device in a therapy
      combined with proprietary creams, in the investigation of a self-treatment
      regimen. A total of 41 adults with mild-to-moderate facial inflammatory acne were
      recruited. The subjects were randomly assigned to combination blue light therapy
      (n = 26) or control (n = 15). Photography was used for qualitative assessment of
      lesion counts, at weeks 1, 2, 4, 8, and 12. All subjects in the treatment cohort
      achieved a reduction in their inflammatory lesion counts after 12 weeks. The mean
      inflammatory lesion counts reduced by 50.02% in the treatment cohort, and
      increased by 2.45% in the control cohort. The reduction in inflammatory lesions
      was typically observable at week-3, and maximal between weeks 8 and 12. The
      treatment is free of pain and side-effects. The blue light device offers a
      valuable alternative to antibiotics and potentially irritating topical
      treatments. Blue light phototherapy, using a narrow-band LED light source,
      appears to be a safe and effective additional therapy for mild to moderate acne.

PMID- 25594128
TI  - A unigene set for European beech (Fagus sylvatica L.) and its use to decipher the
      molecular mechanisms involved in dormancy regulation.
AB  - Systematic sequencing is the method of choice for generating genomic resources
      for molecular marker development and candidate gene identification in nonmodel
      species. We generated 47,357 Sanger ESTs and 2.2M Roche-454 reads from five cDNA
      libraries for European beech (Fagus sylvatica L.). This tree species of high
      ecological and economic value in Europe is among the most representative trees of
      deciduous broadleaf forests. The sequences generated were assembled into 21,057
      contigs with MIRA software. Functional annotations were obtained for 85% of these
      contigs, from the proteomes of four plant species, Swissprot accessions and the
      Gene Ontology database. We were able to identify 28,079 in silico SNPs for future
      marker development. Moreover, RNAseq and qPCR approaches identified genes and
      gene networks regulated differentially between two critical phenological stages
      preceding vegetative bud burst (the quiescent and swelling buds stages).
      According to climatic model-based projection, some European beech populations may
      be endangered, particularly at the southern and eastern edges of the European
      distribution range, which are strongly affected by current climate change. This
      first genomic resource for the genus Fagus should facilitate the identification
      of key genes for beech adaptation and management strategies for preserving beech
      adaptability.

PMID- 25594130
TI  - Intense focused ultrasound for facial tightening: histologic changes in 11
      Patients.
AB  - INTRODUCTION: Intense focused ultrasound (IFUS) is a novel modality for treating
      skin laxity that produces thermal effects at various depths while sparing the
      overlying tissue. This study assessed histologic changes and the safety and
      efficacy of intense focused ultrasound (Doublo(TM), HIRONIC Co., Sungnam, Korea)
      for tightening of facial skin in Asian patients. METHODS: Eleven patients with
      facial laxity were treated with IFUS and evaluated before and after treatment.
      Mean age was 46 years (range, 35-64 years). Two available hand-pieces with
      different focal depths (3 mm and 4.5 mm) were used with three to five passes 1-2
      mm apart. Outcome assessment included photographic evaluation by two blinded
      investigators, skin biopsies before and two months after treatment, and patient
      satisfaction. RESULTS: Subjective and objective analyses showed 63.6% and 72.7%
      improvement at the two-month evaluation, respectively. Histologic evaluation by
      hematoxylin and eosin (H&E) and Masson's trichrome staining showed increased
      collagen fibers in the lower dermis and between fat layers. DISCUSSION AND
      CONCLUSIONS: Intense focused ultrasound can be used as a non-invasive skin
      tightening technique in Asian patients. It induced collagen generation in the
      dermis and fat layers and was effective and safe in our study population.

PMID- 25594131
TI  - From commensalism to mutualism: integrating the microbial ecology, building
      science, and indoor air communities to advance research on the indoor microbiome.

PMID- 25594132
TI  - Response to Miller.

PMID- 25594133
TI  - Exploring carer perceptions of training in out-of-hospital use of buccal
      midazolam for emergency management of seizures (2008-2012).
AB  - AIM: This study aims to explore carer perceptions of training in out-of-hospital
      use of buccal midazolam for emergency management of seizures. METHODS: A random
      sample of 100 families (from n = 198) who underwent training at the Sydney
      Children's Hospitals Network, Randwick campus (2008-2012) were invited to
      participate in a telephone questionnaire. RESULTS: Sixty-three carers
      participated. Thirty-three children were female, median age at training was 4
      years and seizure onset 2.75 years. Seizures were generalised in 26 children and
      focal in 37. Common reasons for prescription included history of prolonged
      seizures (38%), recent diagnosis of epilepsy (33%) and overseas travel (11%).
      Ninety-eight per cent of carers reported that training instructions were clear,
      and 94% reported the risks of using benzodiazepines were satisfactorily
      explained. Ninety per cent felt confident to administer the drug following
      training and 62% completed first aid training as recommended. Suggestions for
      improvement included follow-up/review and additional demonstration/practice.
      Twenty-one carers (33%) reported giving buccal midazolam a median five times, 67%
      reported it was effective in terminating the seizure and 71% called an ambulance
      as instructed. Problems reported in administration included excessive secretions
      and difficulties drawing up the solution. One child experienced breathing
      difficulties requiring oxygen by the paramedics. Four children were admitted to
      children's intensive care unit with status epilepticus requiring intubation.
      CONCLUSIONS: Training for out-of-hospital use of buccal midazolam was considered
      valuable by carers. Only a third of the sample subsequently used midazolam. Half
      of these carers reported problems in administration and one reported respiratory
      difficulty. These results highlight the importance of drug safety and efficacious
      training programmes.

PMID- 25594134
TI  - Boronate based metal-free platform for diphosphate-specific molecular
      recognitions.
AB  - A reversible boronate-diol interaction provides a versatile synthetic platform
      for molecular recognitions whose binding specificity can be molecularly tailored.
      We found that boronate derivatives with relatively strong acidity generally
      undergo a diphosphate-specific recognition among other phosphates under weakly
      acidic pH conditions, a feature relevant to DNA sequencing. (11)B and (31)P NMR
      studies identified "tetrahedral boronate and divalent diphosphate" as a pair
      responsible for forming a 1:1 stoichiometric complex, which manifests as a unique
      pH-dependent stability. 

PMID- 25594135
TI  - Measuring the effectiveness of a revised clinical practice guideline for the pre
      hospital management of supraventricular tachycardia.
AB  - OBJECTIVE: To evaluate the effect of changes to the pre-hospital management of
      patients with supraventricular tachycardia (SVT) following intervention with a
      revised Clinical Practice Guideline (CPG). The major CPG revisions were removal
      of verapamil, addition of adenosine and an emphasis on Valsalva manoeuvre.
      METHOD: We undertook a retrospective case study using data collected by
      paramedics. All adult patients attended by paramedics from the periods 14
      February 2012 to 14 September 2012 (old CPG) and 14 February 2013 to 14 September
      2013 (revised CPG) were included. Patients were excluded if SVT was not recorded
      during initial assessment on a hardcopy ECG. Management guided by the old and
      revised CPGs was compared: reversion effectiveness, elements of therapy
      associated with reversion effectiveness and adverse events. Logistic regression
      determined patient factors significantly associated with reversion. RESULTS:
      Patients were predominantly women, aged approximately 57 years old and most lived
      in the Victorian metropolitan region. Vagal manoeuvre use and effectiveness
      decreased in the post-intervention group. Fewer patients in the post-intervention
      group (141/420, 33.6%) remained in SVT on arrival at hospital compared with the
      pre-intervention group (205/403, 50.8%). Initial heart rate >170/min and longer
      scene time were 2.6 and 1.05 times more likely to result in reversion,
      respectively. CONCLUSION: The revised CPG improved pre-hospital SVT reversion
      success. This expansion of practice has not demonstrated improvements to
      utilisation or effectiveness of the Valsalva manoeuvre. Adenosine is effective
      and safe for pre-hospital use.

PMID- 25594136
TI  - Enzymatic mechanism of copper-containing nitrite reductase.
AB  - Copper-containing nitrite reductases (CuNiRs) catalyze the reduction of nitrite
      to nitric oxide, a key step in the denitrification process that maintains balance
      between organic and inorganic nitrogen. Despite their importance, their
      functioning is not well understood. In this work, we carry out first-principles
      calculations and show that the available structural data are consistent only with
      a single mechanism. For this mechanism, we determine the activation energies,
      transition states, and minimum energy pathways of CuNiR. The calculations lead to
      an updated enzymatic mechanism and resolve several controversial issues. In
      particular, our work identifies the origins of the two protons necessary for the
      enzymatic function and shows that the transformation from the initial O
      coordination of substrate to the final N-coordination of product is achieved by
      electron transfer from T1 copper to T2 copper, rather than by the previously
      reported side-on coordination of a NO intermediate, which only takes place in the
      reduced enzyme. We also examine the role of structural change in the critical
      residue Asp(98), reported in one experimental study, and find that while the
      structural change affects the energetics of substrate attachment and product
      release at the T2 copper reaction center, it does not significantly affect the
      activation energy and reaction pathways of the nitrite reduction process. 

PMID- 25594137
TI  - Association between pulse pressure and risk of hospital admissions for
      cardiovascular events among people with Type 2 diabetes: a population-based case
      control study.
AB  - AIM: To investigate the association between pulse pressure and risk of
      hospitalization for cardiovascular events among people with Type 2 diabetes.
      METHODS: A population-based case-control study was carried out using data from
      medical databases. A total of 588 people with Type 2 diabetes from 18 general
      practices in Cambridgeshire recorded a first hospitalization for a cardiovascular
      event between 2009 and 2011, and a total of 2920 age-matched, gender-matched and
      practice-matched control subjects with Type 2 diabetes were selected based on
      risk-set sampling. Pulse pressure was assessed before admission in 2008-2009.
      Further dose-response relationships between pulse pressure and risks were
      explored using spline models. RESULTS: There was a non-linear relationship
      between pulse pressure and the risk of hospitalization for a cardiovascular event
      (P < 0.001 for linearity test). The pulse pressure associated with the lowest
      risk of hospitalization for a cardiovascular event was 61 (95% CI 57-63) mmHg.
      CONCLUSION: In people with Type 2 diabetes, pulse pressure is a good predictor of
      risk of hospitalization for cardiovascular events. The risk is lowest with a
      pulse pressure of 57-63 mmHg.

PMID- 25594138
TI  - Influence of Occlusal Force on Electroencephalograms in Edentulous Patients.
AB  - PURPOSE: This study explored the effect of improved occlusal force resulting from
      complete denture treatment on electroencephalogram (EEG) findings to determine if
      such an outcome is a factor contributing to activation of synaptic/neuronal
      dysfunction in the brain. MATERIALS AND METHODS: Twenty-three individuals with
      complete upper and lower dentures who visited the Department of Removable
      Prosthodontics at Tsurumi University Dental Hospital were included in this study.
      The Dental Prescale Occluzer FPD-705 system was used to perform an objective
      measurement of occlusal force before and after denture treatment. EEGs were
      recorded for 3 minutes in patients receiving complete dentures before and after
      denture treatment. Then, Dalpha values were calculated using a diagnosis method
      of neuronal dysfunction analysis to evaluate changes in synaptic/neuronal
      dysfunction of the brain. To investigate whether occlusal force affects Dalpha,
      Spearman's rank correlation coefficient (alpha = 0.05) was used to test the
      association between occlusal force (N) and Dalpha based on the rates of change in
      occlusal force and Dalpha calculated by dividing the measurement values after
      denture treatment by the measurement values before denture treatment. RESULTS:
      Medial occlusal force increased from 184.9 N before treatment to 277.2 N after
      treatment. A statistically significant increase in occlusal force (p < 0.05) was
      observed, with a total of 22 participants exhibiting increased occlusal force
      after denture treatment. The medial Dalpha value increased from 0.943 before
      treatment to 0.957 after treatment. A statistically significant increase in
      Dalpha (p < 0.05) was observed, and a total of 19 participants exhibited
      increased Dalpha values after denture treatment. The regression line was
      calculated as Y = 14.049X - 12.450. As occlusal force increased, Dalpha values
      increased as well. A significant positive correlation was observed between
      occlusal force and Dalpha (r = 0.498, p < 0.05). CONCLUSIONS: A positive
      correlation was observed between improved occlusal force attained via complete
      denture treatment and the activation of Dalpha. This finding reveals occlusal
      force as a denture treatment outcome that contributes to the activation of
      synaptic/neuronal dysfunction in the brain.

PMID- 25594139
TI  - Cross-talks between c-Kit and PKC isoforms in HMC-1(560) and HMC-1(560,816)
      cells. Different role of PKCdelta in each cellular line.
AB  - The c-kit inhibitor STI571 represents one of the most important treatments for
      patients with mastocytosis. However, intracellular pathways modulated by this
      compound are not completely defined. Here, STI571 effect on Protein Kinase C
      (PKC) regulation is determined in HMC-1 mast cell lines. STI571 activates
      PKCdelta isoform resulting in HMC-1(560) apoptosis. The apoptosis observed is
      PKCdelta-dependent, since PKCdelta-silencing avoids STI571 effect. c-kit
      inhibition implies nuclear PKCdelta translocation characterized by a clear
      dependence on actin cytoskeleton integrity in HMC-1(560) cell line, but not in
      HMC-1(560,816). Therefore, PKCdelta modulations can lead to a serious decrease in
      STI571 treatment-effectiveness. 

PMID- 25594140
TI  - Self-reported distress in patients with ovarian cancer: is it related to disease
      status?
AB  - OBJECTIVE: Patients with epithelial ovarian cancer have a poor prognosis and
      often undergo intensive treatment. These patients are therefore at risk for
      experiencing distress and reduced quality of life. The aim of this study was to
      explore the self-reported distress severity, experienced problems, and quality of
      life in relation to their disease status. METHODS: This cross-sectional study was
      conducted in 2011 at a University Medical Center. Women with ovarian cancer (n =
      273), both during and after treatment, were asked by mail to fill in self-report
      questionnaires. Distress was measured using with the Distress Thermometer (DT),
      Hospital Anxiety and Depression Scale, and Impact of Event Scale. Problems and
      quality of life were assessed with the problem list of the DT, and European
      Organization for Research and Treatment of Cancer Quality of Life C-30 and OV28.
      RESULTS: The questionnaire data of 104 patients were analyzed. Screening with the
      DT revealed distress in 32% [mean (SD), 3.1 (2.6)]. Distress was found with the
      Hospital Anxiety and Depression Scale in 14% [8.6 (5.9)] and with the Impact of
      Event Scale in 18% of the patients [17.5 (15.5)]. No significant differences were
      found in distress severity and self-reported problems between patients with and
      without recurrence. In both groups, the problems fatigue, condition, and
      neuropathy were most reported. Patients with distress (DT >= 5) experienced
      significantly worse functioning, more problems, and lower quality of life than
      patients without distress (P < 0.01). CONCLUSIONS: This study showed that disease
      status in patients with ovarian cancer seems to have no influence on distress,
      quality of life, and the problems encountered. However, distressed patients
      experienced more problems, with physical and emotional functioning, and had lower
      quality of life. The problems fatigue, physical condition, and neuropathy are the
      most prevailing.

PMID- 25594141
TI  - Clinical significance of the resistance proteins LRP, Pgp, MRP1, MRP3, and MRP5
      in epithelial ovarian cancer.
AB  - OBJECTIVE: This study aimed to evaluate the correlation between the expressions
      of lung resistance protein (LRP), P-glycoprotein (Pgp), multidrug resistance
      associated protein (MRP)-1, MRP3, and MRP5 and histopathological parameters and
      clinical outcome, and to determine the predictive and prognostic value of these
      transport proteins in patients with ovarian cancer. METHODS: Tumor samples from
      111 chemonaive patients with epithelial ovarian cancer who underwent primary
      surgery from 2006 to 2010 were immunohistochemically stained for LRP, Pgp, MRP1,
      MRP3, and MRP5 expressions. RESULTS: MRP1 expression was greater among patients
      with late disease than among patients with early stage ovarian cancer
      [International Federation of Gynecology and Obstetrics (FIGO) I + II, 71.6%
      (confidence interval, 60-100); FIGO III + IV, 83.6% (confidence interval, 100
      100); P = 0.03]. The histological subtype correlated with the expressions of LRP,
      Pgp, MRP1, and MRP3. Relapse of disease during the next 24 months occurred more
      often among patients with higher Pgp and MRP1 than among patients with lower Pgp
      and MRP1 expressions. FIGO stage, histological type, debulking efficiency, strong
      Pgp expression, and strong MRP1 expression correlated significantly with shorter
      progression-free survival (log-rank test, P = 0.001, P = 0.004, P = 0.001, P =
      0.051, and P = 0.046, respectively). FIGO stage, histological type, debulking
      efficiency, and strong MRP1 expression correlated with poor patient survival (log
      rank test, P = 0.001, P = 0.042, P = 0.005, and P = 0.018, respectively).
      CONCLUSIONS: Pgp and MRP1 expressions were clinically significant in patients
      with ovarian cancer. Pgp and MRP1 may be reliable, independent predictive and
      prognostic factors regarding the clinical outcome of ovarian cancer. MRP3 is less
      important as a predictive and prognostic factor than MRP1 expression. MRP5 and
      LRP expressions were not applicable prognostic parameters regarding ovarian
      cancer.

PMID- 25594142
TI  - Addressing challenges in future surveillance after surgery for early-stage
      cervical cancer.
AB  - OBJECTIVE: This study examines surveillance after early-stage cervical cancer
      surgery. Since the 1980s, the value of surveillance has been discussed
      continuously. The main question explored is whether surveillance serves the
      purpose of ensuring early diagnosis of recurrence. MATERIALS AND METHODS: A
      retrospective cohort study included 389 women with cervical cancer who underwent
      surgery as the primary treatment modality at the Department of Obstetrics and
      Gynecology, Aarhus University Hospital, Denmark, from 1996 to 2011. We used data
      from patient files and the Danish National Pathology Data Bank. The cumulative
      risk was estimated by the Kaplan-Meier method and tested by the log-rank test.
      RESULTS: Forty-three women (11%) had recurrence. Only 27% of the recurrent cases
      were diagnosed at a scheduled surveillance appointment, but they were often
      asymptomatic and seemed to have a better outcome after treatment compared with
      the recurrent cases diagnosed at self-referral.The 5-year survival was overall
      91.3%, recurrence-free survival was 96%, and cancer-specific survival was 54%.
      The median recurrence-free interval was 23 months (range, 4-144) for the
      symptomatic patients and 14 months (range, 4-48) for the asymptomatic patients.
      The median survival after recurrence was 12 months (range, 2-132) for the
      symptomatic patients and 156 months (range, 40-180) for the asymptomatic
      patients. CONCLUSIONS: At the moment, neither the value of surveillance nor the
      significance of self-referral related to survival after recurrence is known. In
      this study, those who are diagnosed with recurrence before symptom onset seem to
      fare better in terms of 5-year survival than those who are diagnosed after self
      referral because of symptoms.

PMID- 25594143
TI  - Clinical characteristics of non-squamous cell carcinoma of the vagina.
AB  - OBJECTIVE: The prognosis and vaginal disease control rate after treatment with
      radiotherapy or concurrent chemoradiotherapy (CCRT) are reported to be worse for
      primary non-squamous cell carcinoma (non-SCC) of the vagina than for squamous
      cell carcinoma (SCC) of the vagina. Our objective was to examine the
      clinicopathological characteristics of primary non-SCC of the vagina and suggest
      an appropriate treatment strategy. MATERIALS AND METHODS: In a retrospective
      chart review, we identified patients with primary vaginal cancer who were treated
      in our hospital between 1990 and 2013. Twelve patients with histologically
      diagnosed non-SCC were identified. None of these cases was associated with in
      utero diethylstilbestrol exposure. Clinical data, including patient
      characteristics, stage, treatment outcome, and the site of recurrence, were
      recorded. RESULTS: The 12 identified cases included 5 of clear cell carcinoma, 3
      of adenocarcinoma, 2 of adenosquamous carcinoma, 1 of carcinosarcoma, and 1 of
      mucinous adenocarcinoma. The most common location of the tumor was the upper one
      third of the vagina (56%). Initial treatment involved surgery in 8 patients.
      Among them, 4 received adjuvant chemotherapy, 3 received adjuvant radiotherapy,
      and 1 received neither. The initial treatment among the remaining 4 patients was
      CCRT in 1, neoadjuvant chemotherapy in 2 (followed by CCRT or surgery), and best
      supportive care in 1. The last 3 patients had lung metastasis. Six patients
      experienced recurrence, including vaginal recurrence in 2 patients and lymphatic
      spread in 4 patients. Five of these 6 patients experienced hematogenous
      metastasis. CONCLUSIONS: Despite the absence of in utero diethylstilbestrol
      exposure in our cases, clear cell adenocarcinoma accounted for 41.7% (5/12)
      cases. A favorable local control rate was achieved in all 12 cases, but the
      incidence of distant metastasis, especially to the lung, was high. Prevention of
      distant metastasis may be the key to treating patients with non-SCC of the
      vagina.

PMID- 25594144
TI  - Gliomatosis peritonei: a particular entity with specific outcomes within the
      growing teratoma syndrome.
AB  - OBJECTIVES: Ovarian immature teratoma may be associated with peritoneal spread
      that could, after adjuvant chemotherapy, develop into disease exclusively
      composed of mature implants (growing teratoma syndrome) and/or gliomatosis
      peritonei (GP), defined as the presence of pure mature glial tissue. However,
      very few specific series are devoted to the outcomes of pure GP. This was the aim
      of the present study. PATIENTS: From 1997 to 2013, data concerning patients
      treated for stage II/III immature teratoma were reviewed. All slides were
      reviewed by an expert pathologist. Patients with ovarian cancer associated with
      peritoneal spread in the form of pure GP (initially if patients were treated
      without adjuvant treatment or after adjuvant chemotherapy if done) were analyzed.
      RESULTS: Ten patients fulfilled the inclusion criteria. The median age of
      patients at diagnosis was 36 years (range, 14-41 years). Six patients had
      undergone a conservative treatment. Five patients had macroscopic residual
      disease at the end of surgery.The median duration of follow-up from the diagnosis
      of GP was 39 months (range, 6-114 months). Six patients had undergone secondary
      surgery. Among them, 5 had incompletely resected macroscopic GP. No patients had
      died of their disease. All patients were asymptomatic at the time of the last
      consultation (1 of them with abnormal radiologic imaging). CONCLUSIONS:
      Gliomatosis peritonei is a particular entity of the condition described as
      growing teratoma syndrome because residual peritoneal disease can be asymptomatic
      totally stable over a long period which raises the question of a more
      conservative surgical approach in patients with massive peritoneal spread.

PMID- 25594145
TI  - Optimal timing for drainage of infected lymphocysts after lymphadenectomy for
      gynecologic cancer.
AB  - BACKGROUND: A lymphocyst (lymphocele) is a common complication of
      lymphadenectomy, which is a widely used surgical method for gynecologic cancers.
      In cases of infected lymphocysts, therapeutic strategies, including the timing
      and duration of antibiotics administration and cyst drainage, may vary depending
      on the physician. The aim of this study was to determine the optimal timing for
      drainage of lymphocysts infected with bacteria resistant to antibiotic treatment.
      MATERIALS AND METHODS: Clinical data for 1175 patients who underwent a
      lymphadenectomy as part of surgery for a gynecologic malignancy between April
      2000 and August 2012 at Osaka University Hospital, Osaka, Japan, were analyzed.
      RESULTS: Of the 282 patients who developed a lymphocyst (24%), 35 with infected
      lymphocysts (12%) were analyzed. Lymphocyst infection was not associated with
      tumor origin, type of hysterectomy, or region of lymphadenectomy (P = 0.81, P =
      0.59, and P = 0.86, respectively). The total treatment period of cases treated
      only with antibiotics tended to be shorter than that of cases treated with
      combined antibiotics and drainage, but the difference was not significant (P =
      0.061). However, for severe cases which needed drainage, initiating the drainage
      by day 5 significantly shortened the total treatment period compared with cases
      started on or after day 6 (P = 0.042). CONCLUSIONS: The appropriate time point
      for initiating lymphocyst drainage has been difficult to determine. The present
      study implies that for severe lymphocyst infections, where drainage is required
      in addition to antibiotics, the earlier the drainage is performed, the shorter
      the treatment period is. Further studies may be required to decide other optimal
      treatment strategies for infected lymphocysts.

PMID- 25594146
TI  - Fimbrial cells exposure to catalytic iron mimics carcinogenic changes.
AB  - OBJECTIVE: Recent evidence strongly suggests that the fallopian tube is a site of
      origin of ovarian cancer. Although histological data show iron deposition in the
      fallopian tubes, its role remains unclear. To establish whether catalytic iron
      has a possible role in ovarian carcinogenesis, we isolated human fimbrial
      secretory epithelial cells (FSECs). METHODS: Fimbrial secretory epithelial cells,
      isolated from women undergoing isteroannessiectomy, were treated with different
      doses of catalytic iron (0.05-100 mM) to study cell viability; NO production;
      p53, Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc protein expressions through Western
      blot analysis; and immunocytochemistry or immunofluorescence. RESULTS: In FSECs
      treated with catalytic iron for up to 6 days, we observed an increase in cell
      viability, NO production, and p53, pan-Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc
      activations (P < 0.05) in a dose-dependent and time-dependent manner. These same
      results were also observed in FSECs maintained for respectively 2 and 4 weeks in
      the absence of catalytic iron after 6 days of stimulation. CONCLUSIONS: Our model
      aimed at studying the main nongenetic risk factor for ovarian cancer, providing
      an alternative interpretation for the role of menstruation in increasing risk of
      this pathology. This in vitro model mimics several features of the precursor
      lesions and opens new scenarios for further investigations regarding the
      correlation between damages produced by repeated retrograde menstruation
      carcinogenic stimuli.

PMID- 25594148
TI  - EPICC study: evaluation of pharmaceutical intervention in cancer care.
AB  - WHAT IS KNOWN AND OBJECTIVES: In cancer care, clinical pharmacists contribute to
      improving prevention and management of drug-related problems (DRPs). The 3-year
      EPICC study (Evaluation of Pharmaceutical Intervention in Cancer Care) aimed to
      collect and analyse pharmaceutical interventions (PIs) in oncology. METHODS: The
      free online version of the French Society of Clinical Pharmacy (SFPC) coding
      system, ACT-IP, was used, supplemented by a standardized dedicated cancer-care
      decision tree. RESULTS: A total of 29,589 medication orders (77,004 anticancer
      drug preparations) were analysed. Eight hundred and ninety-four PIs were
      recorded. ACT-IP identified 54.1% of DRPs as concerning over- or underdosage. The
      standardized dedicated cancer-care decision tree identified the three principal
      causes of dosage problems: 50.2% due to miscalculation, 20% to omission of dose
      adjustment and 12% to poor choice of antineoplastic regimen. About 13.8% of DRPs
      were adverse effects and 3.9% were drug-drug interactions. The decision tree
      showed that 22% of adverse events could be circumvented by a switch within the
      same drug family and 72% of drug-drug interactions would have led to increased
      neoplastic toxicity. DISCUSSION: Pharmaceutical analysis of prescription forms
      contributes to medication safety in cancer care, and the present dedicated
      decision tree highlights additional information about DRPs and PIs. The DRP rate
      (3% of prescriptions) was consistent with the literature. The pharmacist has a
      role to play in optimizing the management of patients with cancer in terms of
      dose adjustment, drug toxicity management, improvement of administration and drug
      drug interactions. WHAT IS NEW AND CONCLUSION: This study, highlighting PIs in
      cancer care, is the first of this scale in terms of number of prescriptions
      analysed (nearly 30 000). Results demonstrated the specificity of DRPs and PIs
      for patients with cancer and the value of a dedicated coding system in cancer
      care.

PMID- 25594149
TI  - Health Insurance, Health Savings Accounts and Healthcare Utilization.
AB  - Assuming symmetric information, we show that a high-deductible health plan (HDHP)
      combined with a tax-favored health savings account (HSA) induces more savings and
      less treatment compared with a full coverage plan under reasonable risk
      preferences. Furthermore, a higher tax subsidy increases savings in any case but
      decreases medical utilization if and only if treatment expenses are above the
      deductible. A larger deductible increases savings but does not necessarily
      decrease healthcare utilization. Whether an HDHP/HSA combination is preferred
      over a full coverage contract depends on absolute risk aversion. A higher tax
      advantage increases the attractiveness of an HDHP/HSA combination, whereas the
      effects of changes in the deductible are ambiguous. The paper shows that a
      potential regulator needs to carefully set the size of the deductible as only in
      a certain corridor of the probability of sickness, its effect on aggregate
      healthcare costs are unambiguously favorable.

PMID- 25594147
TI  - A phase I-II evaluation of veliparib (NSC #737664), topotecan, and filgrastim or
      pegfilgrastim in the treatment of persistent or recurrent carcinoma of the
      uterine cervix: an NRG Oncology/Gynecologic Oncology Group study.
AB  - PURPOSE: The aim of this study was to evaluate the tolerability and efficacy of
      poly(ADP-ribose) polymerase (PARP) inhibition by veliparib during cytotoxic
      topotecan administration with filgrastim or pegfilgrastim neutrophil support in
      women with persistent or recurrent uterine cervix cancer. EXPERIMENTAL DESIGN:
      This phase I-II trial examined twice-daily oral veliparib (10 mg) given during
      once-daily intravenous topotecan (0.6 mg/m2) on days 1 to 5 of each treatment
      cycle. Cycles were repeated every 21 days until disease progression or until
      toxicity prohibited further therapy. Toxicity and objective response rate were
      primary endpoints. RESULTS: Twenty-seven women were enrolled. Frequently reported
      grade 3 or higher treatment-related toxicities were anemia (59%),
      thrombocytopenia (44%), leukopenia (22%), and neutropenia (19%). There were 2
      partial responses (7% [90% confidence interval, 1%-22%]). Four patients had a
      disease progression date more than 6 months after the start of veliparib
      topotecan therapy. Patients with low immunohistochemical expression (0-1+) of
      PARP-1 in their primary uterine cervix cancer were more likely to have a longer
      progression-free interval (hazard ratio, 0.25; P = 0.02) and survival (hazard
      ratio, 0.12; P = 0.005) after veliparib-topotecan therapy. CONCLUSIONS: Clinical
      activity of a veliparib-topotecan combination was minimal in women with
      persistent or recurrent uterine cervix cancer. Women whose uterine cervix cancers
      express PARP-1 at low levels may benefit preferentially from PARP inhibitors
      combined with cytotoxic therapies, suggesting further study of PARP expression as
      an integral triage biomarker.

PMID- 25594151
TI  - Angle dependence of argon gas cluster sputtering yields for organic materials.
AB  - The first angle-dependent measurements of the sputtering yield of an organic
      material using argon gas cluster ions under a wide range of conditions are
      reported in order to develop an analytical description of the behavior important
      for the development of the application of secondary ion mass spectrometry to
      organic and biological systems. Data are presented for Irganox 1010 using argon
      gas cluster ion beams of 5 and 10 keV energy, E, with cluster sizes, n, from 1000
      to 5000. The measurements are conducted in an X-ray photoelectron spectrometer
      for a range of angles from 0 to 80 degrees  from the surface normal. The results
      support the Universal Equation for argon gas cluster sputtering yields with the
      angle dependence incorporated into the equation via a simple angle dependence of
      the parameter A. This explains how and why the angular dependence of the
      sputtering yield changes significantly with increasing E/n. These results are
      also accurately confirmed using the published measurements for polystyrene by
      Rading et al. 

PMID- 25594150
TI  - Screening for AZFc partial deletions in Dravidian men with nonobstructive
      azoospermia and oligozoospermia.
AB  - CONTEXT: Dravidians are the predominant population residing in South India with a
      diverse genetic structure. Considering various genetic discoveries taking place
      today, it is evident that deletions in the AZFc region are the most common cause
      of severe spermatogenic failure (SSF) in various populations studied. However, it
      is significant to note that there is a paucity of scientific literature on AZFc
      subdeletion screening among the Dravidian population. OBJECTIVE: To investigate
      the prevalence and association of AZFc subdeletion patterns among Dravidian men
      with nonobstructive azoospermia (NOA) and oligozoospermia. METHODS: A population
      of 354 subjects, including 120 patients with NOA, 109 with oligozoospermia, and
      125 normal male controls, were screened using locus-specific sequence tag site
      markers. RESULTS: We found 21 (9.17%) patients with classical AZF deletion, while
      no deletions were observed in controls. After excluding the samples with AZF
      deletions, the remaining 208 infertile and 125 control samples were screened for
      partial AZFc deletions using a standardized multiplex polymerase chain reaction
      and on analysis revealed that 13 (6.25%) of the infertile samples possessed gr/gr
      subdeletions and 15 (7.21%) of the infertile samples possessed b2/b3
      subdeletions. Six (4.8%) of the normal samples were found to carry gr/gr
      subdeletions and two (1.6%) had b2/b3 deletions. The b1/b3 deletion was not
      observed in any of the patient and control samples screened. CONCLUSION: Our
      finding shows that there is a strong association between b2/b3 subdeletion and
      SSF in the Dravidian population (odds ratio, 4.78; 95% confidence interval 1.07
      21.26) (p=0.018). Further studies, including gene copy typing for DAZ and CDY
      genes and a comprehensive haplogrouping analysis, are recommended in a large and
      well-selected patient group to elude the genetic mechanism behind this
      association.

PMID- 25594152
TI  - Patient-tailored combinations of systemic and topical preparations for localized
      peripheral neuropathic pain: a two-case report.
AB  - This report describes two patients with peripheral neuropathic pain (PNP): a 43
      year-old man with upper leg PNP and a 75-year-old woman with post herpetic
      neuralgia of the perineum and vagina. Pain was inadequately managed in both
      patients for a long time. A patient-tailored approach, including a combination of
      systemic and topical compounds, required multiple adjustments for each patient
      before finally achieving adequate pain control. The first patient achieved pain
      control with a combination of systemically-administered drugs: dipyrone (1 g 3
      times a day), pregabalin (300 mg twice a day), duloxetine (60 mg once daily in
      the morning), and dextromethorphan (60 mg 3 times/day), plus topical compounds
      (10% ketamine, 5% lidocaine, and 10% ketoprofen) in penetrating enhancing gel,
      and sublingual ketamine (10 mg) for breakthrough pain. The second patient
      achieved optimal pain control with dipyrone (500 mg three times per day),
      pregabalin (150 mg twice a day), dextromethorphan (60 mg three times per day),
      plus topical compounds (10% ketamine, 0.3% clonidine, 5% diclofenac) in a
      penetrating enhancing gel. Notably, the individualized approach described herein
      was made possible through collaboration between a public health pain specialist
      and a private sector compounding pharmacist, highlighting the importance of such
      infrequent but, highly desirable collaborations.

PMID- 25594153
TI  - First-person and third-person verbs in visual motion-perception regions.
AB  - Verb-related activity is consistently found in the left posterior lateral cortex
      (PLTC), encompassing also regions that respond to visual-motion perception.
      Besides motion, those regions appear sensitive to distinctions among the entities
      beyond motion, including that between first- vs. third-person ("third-person
      bias"). In two experiments, using functional magnetic resonance imaging (fMRI),
      we studied whether the implied subject (first/third-person) and/or the semantic
      content (motor/non-motor) of verbs modulate the neural activity in the left PLTC
      regions responsive during basic- and biological-motion perception. In those
      sites, we found higher activity for verbs than for nouns. This activity was
      modulated by the person (but not the semantic content) of the verbs, with
      stronger response to third- than first-person verbs. The third-person bias
      elicited by verbs supports a role of motion-processing regions in encoding
      information about the entity beyond (and independently from) motion, and sets in
      a new light the role of these regions in verb processing. 

PMID- 25594154
TI  - The relationship between transitional motor skills and locomotion.
AB  - This study explores whether transitional skills and sitting correlate with
      locomotion onset. The development of eight infants was followed. Most
      transitional skills correlated with locomotor skills. Sitting and rolling did
      not. Transitional skills may resemble the control needed for locomotion more
      closely than sitting. 

PMID- 25594155
TI  - Third-body effects of native surfactants on Pt nanoparticle electrocatalysts in
      proton exchange fuel cells.
AB  - The residual surfactant organic molecules on electrocatalysts are expected to
      enhance the tolerance to specific anion adsorption, whereas the surfactants have
      been generally regarded as contaminants that block active surfaces. In this
      study, the Pt nanoparticles with adsorbed surfactants were prepared, and their
      electrochemical characteristics at various phosphoric acid concentrations were
      studied by the half-cell test. The third-body effect was experimentally confirmed
      by the single-cell test with a phosphoric acid-doped polybenzimidazole membrane. 

PMID- 25594157
TI  - Tuning the surface properties of novel ternary iron(III) fluoride-based catalysts
      using the template effect of the matrix.
AB  - Sol-gel prepared ternary FeF3-MgF2 materials have become promising heterogeneous
      catalysts due to their porosity and surface Lewis/Bronsted acidity (bi-acidity).
      Despite the good catalytic performance, nanoscopic characterisations of this type
      of material are still missing and the key factors controlling the surface
      properties have not yet been identified, impeding both a better understanding and
      further development of ternary fluoride catalysts. In this study, we
      characterised the interaction between the bi-acidic component (FeF3) and the
      matrix (MgF2) on the nano-scale. For the first time, the formation pathway of
      FeF3-MgF2 was profiled and the template effect of MgF2 during the synthesis
      process was discovered. Based on these new insights two novel materials, FeF3
      CaF2 and FeF3-SrF2, were established, revealing that with decreasing the atomic
      numbers (from Sr to Mg), the ternary fluorides exhibited increasing surface
      acidity and surface area but decreasing pore size. These systematic changes gave
      rise to a panel of catalysts with tuneable surface and bulk properties either by
      changing the matrix alkaline earth metal fluoride or by adjusting their ratios to
      Fe or both. The template effect of the alkaline earth metal fluoride matrix was
      identified as the most probable key factor determining the surface properties and
      further influencing the catalytic performance in ternary fluoride based
      catalysts, and paves the way to targeted design of next-generation catalysts with
      tunable properties. 

PMID- 25594156
TI  - The Arabidopsis leucine-rich repeat receptor-like kinase MUSTACHES enforces
      stomatal bilateral symmetry in Arabidopsis.
AB  - Stomata display a mirror-like symmetry that is adaptive for shoot/atmosphere gas
      exchange. This symmetry includes the facing guard cells around a lens-shaped and
      bilaterally symmetric pore, as well as radially arranged microtubule arrays that
      primarily originate at the pore and then grow outwards. Mutations in MUSTACHES
      (MUS), which encodes a leucine-rich repeat receptor-like kinase, disrupt this
      symmetry, resulting in defects ranging from skewed pores and abnormally focused
      and depolarized radial microtubule arrays, to paired guard cells that face away
      from each other, or a severe loss of stomatal shape. Translational
      MUSproMUS:tripleGFP fusions are expressed in cell plates in most cells types in
      roots and shoots, and cytokinesis and cell plates are mostly normal in mus
      mutants. However, in guard mother cells, which divide and then form stomata, MUS
      expression is notably absent from new cell plates, and instead is peripherally
      located. These results are consistent with a role for MUS in enforcing wall
      building and cytoskeletal polarity at the centre of the developing stoma via
      signalling from the vicinity of the guard cell membrane. 

PMID- 25594158
TI  - The role of bond tangency and bond gap in hard sphere crystallization of chains.
AB  - We report results from Monte Carlo simulations on dense packings of linear,
      freely-jointed chains of hard spheres of uniform size. In contrast to our past
      studies where bonded spheres along the chain backbone were tangent, in the
      present work a finite tolerance in the bond is allowed. Bond lengths are allowed
      to fluctuate in the interval [sigma, sigma + dl], where sigma is the sphere
      diameter. We find that bond tolerance affects the phase behaviour of hard-sphere
      chains, especially in the close vicinity of the melting transition. First, a
      critical dl(crit) exists marking the threshold for crystallization, whose value
      decreases with increasing volume fraction. Second, bond gaps enhance the onset of
      phase transition by accelerating crystal nucleation and growth. Finally, bond
      tolerance has an effect on crystal morphologies: in the tangent limit the
      majority of structures correspond to stack-faulted random hexagonal close packing
      (rhcp). However, as bond tolerance increases a wealth of diverse structures can
      be observed: from single fcc (or hcp) crystallites to random hcp/fcc stackings
      with multiple directions. By extending the simulations over trillions of MC steps
      (10(12)) we are able to observe crystal-crystal transitions and perfection even
      for entangled polymer chains in accordance to the Ostwald's rule of stages in
      crystal polymorphism. Through simple geometric arguments we explain how the
      presence of rigid or flexible constraints affects crystallization in general
      atomic and particulate systems. Based on the present results, it can be concluded
      that proper tuning of bond gaps and of the connectivity network can be a
      controlling factor for the phase behaviour of model, polymer-based colloidal and
      granular systems. 

PMID- 25594159
TI  - Cardiac complications in relapsed and refractory multiple myeloma patients
      treated with carfilzomib.

PMID- 25594160
TI  - Efficient immobilization of acetylcholinesterase onto amino functionalized carbon
      nanotubes for the fabrication of high sensitive organophosphorus pesticides
      biosensors.
AB  - This work introduced an efficient immobilization of acetylcholinesterase (AChE)
      onto amino functionalized carbon nanotubes (CNT-NH2), in order to fabricate high
      sensitive and practical organophosphorus pesticide (OPs) biosensors. Compared
      with the pristine, -COOH and -OH decorated CNTs, there were larger amount of
      enzymes adsorbed on the surface of CNT-NH2 with a favorable orientation and the
      best amperometric response was obtained on the AChE/CNT-NH2/GC electrode.
      Furthermore, the biosensor modified with CNT-NH2 showed a high affinity to
      acetylthiocholine chloride (ATCh) and could catalyze the hydrolysis of ATCh with
      an apparent Michaelis-Menten constant (Km) value of 67.4 uM. Using paraoxon as a
      model compound, wide linear ranges from 0.2 nM to 1 nM and 1 nM to 30 nM, and a
      low detection limit of 0.08 nM were obtained with satisfactory reproducibility
      and stability. Moreover, the biosensor had also been successfully employed for
      the determination of low concentrations of pesticides in real vegetable samples.
      This method could be extended to other functionalized nano-materials for their
      application in constructing biosensors.

PMID- 25594161
TI  - DNA aptamers selection and characterization for development of label-free
      impedimetric aptasensor for neurotoxin anatoxin-a.
AB  - High affinity DNA aptamers against anatoxin-a (ATX), the smallest potent
      neurotoxin (Mol. Wt, 165.23 Da) were selected and identified in vitro using the
      systematic evolution of ligands by exponential enrichment (SELEX) approach.
      Aptamers with dissociation constants (Kd) of nanomolar range were isolated. The
      aptamer sequence of highest affinity was used to design a label-free impedance
      based aptasensor to assay ATX, for which there are no reported biosensors so far.
      The aptamer self assembled monolayer is formed on a gold electrode using the
      disulfide modified aptamer. The assembly process of the aptasensor was
      characterized using cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS). Upon ATX binding to the immobilized aptamer, a significant
      decrease in the electron-transfer resistance was observed as a result of the
      aptamer conformation change, which is used as the sensor signal. The aptasensor
      showed a limit of detection of 0.5 nM and a wide linear range for ATX
      concentrations between 1 nM and 100 nM. The Kd of anti-ATX aptamer was calculated
      by electrochemical methods as well as the fluorescence. Interestingly, the Kd
      that was calculated from the aptasensor signal showed a lower value implying that
      the anchoring of the aptamer on the Au surface enhanced its affinity to ATX. The
      ATX aptasensor showed high stability as well as high specificity against common
      cynaobacterial toxins. Further development of biosensors that use anatoxin-a
      binding aptamers as a new recognition receptors could provide potential
      alternatives to the traditional assays for fast and simple monitoring of anatoxin
      a.

PMID- 25594162
TI  - Theoretical prediction of the host-guest interactions between novel
      photoresponsive nanorings and C60: a strategy for facile encapsulation and
      release of fullerene.
AB  - A series of photoresponsive-group-containing nanorings hosts with 12~14 A in
      diameter is designed by introducing different number of azo groups as the
      structural composition units. And the host-guest interactions between fullerene
      C60 and those nanoring hosts were investigated theoretically at M06-2X/6
      31G(d)//M06-L/MIDI! and wB97X-D/6-31G(d) levels. Analysis on geometrical
      characteristics and host-guest binding energies revealed that the designed
      nanoring molecule (labeled as 7) which is composed by seven azo groups and seven
      phenyls is the most feasible host for encapsulation of C60 guest among all
      candidates. Moreover, inferring from the simulated UV-vis-NIR spectroscopy, the
      C60 guest could be facilely released from the cavity of the host 7 via
      configuration transformation between trans-form and cis-form of the host under
      the 563 nm photoirradiation. Additionally, the frontier orbital features, weak
      interaction regions, infrared, and NMR spectra of the C60@7 host-guest complex
      have also been investigated theoretically.

PMID- 25594163
TI  - Water dynamics in different biochar fractions.
AB  - Biochar is a carbonaceous porous material deliberately applied to soil to improve
      its fertility. The mechanisms through which biochar acts on fertility are still
      poorly understood. The effect of biochar texture size on water dynamics was
      investigated here in order to provide information to address future research on
      nutrient mobility towards plant roots as biochar is applied as soil amendment. A
      poplar biochar has been stainless steel fractionated in three different textured
      fractions (1.0-2.0 mm, 0.3-1.0 mm and <0.3 mm, respectively). Water-saturated
      fractions were analyzed by fast field cycling (FFC) NMR relaxometry. Results
      proved that 3D exchange between bound and bulk water predominantly occurred in
      the coarsest fraction. However, as porosity decreased, water motion was mainly
      associated to a restricted 2D diffusion among the surface-site pores and the bulk
      site ones. The X-ray MU-CT imaging analyses on the dry fractions revealed the
      lowest surface/volume ratio for the coarsest fraction, thereby corroborating the
      3D water exchange mechanism hypothesized by FFC NMR relaxometry. However, multi
      micrometer porosity was evidenced in all the samples. The latter finding
      suggested that the 3D exchange mechanism cannot even be neglected in the finest
      fraction as previously excluded only on the basis of NMR relaxometry results. X
      ray MU-CT imaging showed heterogeneous distribution of inorganic materials inside
      all the fractions. The mineral components may contribute to the water relaxation
      mechanisms by FFC NMR relaxometry. Further studies are needed to understand the
      role of the inorganic particles on water dynamics.

PMID- 25594164
TI  - Predicting community participation after spinal cord injury in Thailand.
AB  - OBJECTIVE: To identify the predictors of community participation after spinal
      cord injury. DESIGN: Cross-sectional design. METHODS: A total of 139 persons with
      spinal cord injury living in the community completed 4 instruments: the Impact on
      Participation and Autonomy (IPA-Thai version), the Craig Hospital Inventory of
      Environmental Factors (CHIEF-SF-Thai version), the Personal Resource
      Questionnaire (PRQ2000-Thai version), and a personal history questionnaire.
      Functional performance was assessed using the Functional Independence Measure
      (FIM) motor subscale. RESULTS: Participants comprised 79% males. Fifty-one
      percent of variance in community participation was explained by social support,
      functional performance, age, and age at time of injury. CONCLUSION: Key
      predictors of community participation were the availability of social support and
      the individual's functional performance. These predictors should be emphasized
      when developing interventions in rehabilitation and community settings.

PMID- 25594165
TI  - Supported Ionic Liquid Membranes and Ion-Jelly(r) Membranes with [BMIM][DCA]:
      Comparison of Its Performance for CO2 Separation.
AB  - In this work, a supported ionic liquid membrane (SILM) was prepared by
      impregnating a PVDF membrane with 1-butyl-3-methylimidazolium dicyanamide
      ([BMIM][DCA]) ionic liquid. This membrane was tested for its permeability to pure
      gases (CO2, N2 and O2) and ideal selectivities were calculated. The SILM
      performance was also compared to that of Ion-Jelly(r) membranes, a new type of
      gelled membranes developed recently. It was found that the PVDF membrane presents
      permeabilities for pure gases similar or lower to those presented by the Ion
      Jelly(r) membranes, but with increased ideal selectivities. This membrane
      presents also the highest ideal selectivity (73) for the separation of CO2 from
      N2 when compared with SILMs using the same PVDF support but with different ionic
      liquids. 

PMID- 25594166
TI  - Effects of alpha-lipoic acid and eicosapentaenoic acid in overweight and obese
      women during weight loss.
AB  - OBJECTIVE: To evaluate the potential body weight-lowering effects of dietary
      supplementation with eicosapentaenoic acid (EPA) and alpha-lipoic acid separately
      or combined in healthy overweight/obese women following a hypocaloric diet.
      METHODS: This is a short-term double-blind placebo-controlled study with parallel
      design that lasted 10 weeks. Of the randomized participants, 97 women received
      the allocated treatment [Control, EPA (1.3 g/d), alpha-lipoic acid (0.3 g/d), and
      EPA+alpha-lipoic acid (1.3 g/d+0.3 g/d)], and 77 volunteers completed the study.
      All groups followed an energy-restricted diet of 30% less than total energy
      expenditure. Body weight, anthropometric measurements, body composition, resting
      energy expenditure, blood pressure, serum glucose, and insulin and lipid profile,
      as well as leptin and ghrelin levels, were assessed at baseline and after
      nutritional intervention. RESULTS: Body weight loss was significantly higher
      (P<0.05) in those groups supplemented with alpha-lipoic acid. EPA supplementation
      significantly attenuated (P<0.001) the decrease in leptin levels that occurs
      during weight loss. Body weight loss improved lipid and glucose metabolism
      parameters but without significant differences between groups. CONCLUSIONS: The
      intervention suggests that alpha-lipoic acid supplementation alone or in
      combination with EPA may help to promote body weight loss in healthy
      overweight/obese women following energy-restricted diets.

PMID- 25594168
TI  - Is it time to change conventional consolidation chemotherapy for acute myeloid
      leukemia in CR1?
AB  - PURPOSE OF REVIEW: Choosing the most appropriate postremission therapy (PRT) for
      a patient with acute myeloid leukemia (AML) in first complete remission remains a
      challenging task. Factors such as risk for disease relapse, nonrelapse mortality
      associated with different PRT approaches, donor availability, prospects for
      salvage should disease relapse, and patient preference all affect PRT choice.
      RECENT FINDINGS: New genetic markers refine AML risk stratification and identify
      patients within the 'classical' risk groups who may benefit from transplant-based
      or chemotherapy-based PRT. The use of minimal residual disease in first remission
      to guide PRT choice and the application of novel, targeted therapies have the
      potential to alter PRT approaches across AML risk groups. The advent of
      alternative donor sources, use of reduced intensity regimens, and improved
      supportive care all affect the availability and safety of transplant-based PRT
      and challenge the relevance of the older legacy 'donor/no-donor' genetically
      randomized trials. SUMMARY: Genetic risk assessment, monitoring of minimal
      residual disease in first remission, use of targeted agents, and the newer
      transplant strategies all have the potential to 'personalize' PRT choice in the
      AML patient. The clinical value of these novel interventions awaits validation in
      prospective, risk-adapted clinical trials.

PMID- 25594167
TI  - A model-based reconstruction for undersampled radial spin-echo DTI with
      variational penalties on the diffusion tensor.
AB  - Radial spin-echo diffusion imaging allows motion-robust imaging of tissues with
      very low T2 values like articular cartilage with high spatial resolution and
      signal-to-noise ratio (SNR). However, in vivo measurements are challenging, due
      to the significantly slower data acquisition speed of spin-echo sequences and the
      less efficient k-space coverage of radial sampling, which raises the demand for
      accelerated protocols by means of undersampling. This work introduces a new
      reconstruction approach for undersampled diffusion-tensor imaging (DTI). A model
      based reconstruction implicitly exploits redundancies in the diffusion-weighted
      images by reducing the number of unknowns in the optimization problem and
      compressed sensing is performed directly in the target quantitative domain by
      imposing a total variation (TV) constraint on the elements of the diffusion
      tensor. Experiments were performed for an anisotropic phantom and the knee and
      brain of healthy volunteers (three and two volunteers, respectively). Evaluation
      of the new approach was conducted by comparing the results with reconstructions
      performed with gridding, combined parallel imaging and compressed sensing and a
      recently proposed model-based approach. The experiments demonstrated improvements
      in terms of reduction of noise and streaking artifacts in the quantitative
      parameter maps, as well as a reduction of angular dispersion of the primary
      eigenvector when using the proposed method, without introducing systematic errors
      into the maps. This may enable an essential reduction of the acquisition time in
      radial spin-echo diffusion-tensor imaging without degrading parameter
      quantification and/or SNR.

PMID- 25594170
TI  - Disentangling inborn and acquired immunity in human twins.
AB  - The human geneticist Archibald Garrod noted in 1931 that, "It is, of necessity,
      no easy matter to distinguish between immunity which is inborn and that which has
      been acquired" (The Inborn Factors in Disease). In this issue of Cell, Brodin et
      al. show that the heritability of blood counts rapidly decreases with age for the
      lymphoid subsets responsible for adaptive immunity, unlike cells from other
      hematopoietic lineages. 

PMID- 25594171
TI  - A protein restriction-dependent sulfur code for longevity.
AB  - The restriction of proteins has recently emerged as the most important factor for
      the beneficial effects of calorie restriction. Hine et al. now provide strong
      evidence for the role of the hydrogen sulfide (H2S) gas in the protective effects
      of calorie and protein restriction against ischemia/reperfusion injury (IRI) but
      also implicate H2S in longevity extension in model organisms. 

PMID- 25594169
TI  - Theory of mind and emotional functioning in fibromyalgia syndrome: an
      investigation of the relationship between social cognition and executive
      function.
AB  - BACKGROUND: Fibromyalgia (FM) is a syndrome primarily characterised by chronic,
      widespread musculoskeletal pain. In the aetiology of this syndrome a crucial role
      is played by complex interactions among biological, genetic, psychological, and
      socio-cultural factors. Recently, researchers have started to explore emotional
      functioning in FM, with their attention focused on alexithymia, a personality
      construct that affects the regulation of a person's own emotions. On the other
      hand, the detection and experience of emotional signals from other people have
      only been sparsely investigated in FM syndrome and no studies have investigated
      the ability to represent other people's mental states (i.e. Theory of Mind, ToM)
      in these patients. Here we present the first study investigating a large set of
      social-cognitive abilities, and the possible relationships between these
      abilities and the performance on executive-function tasks, in a homogenous sample
      of patients with FM. METHODOLOGY: Forty women with FM and forty-one healthy women
      matched for education and age were involved in the study. Social cognition was
      assessed with a set of validated experimental tasks. Measures of executive
      function were used to test the correlations between this dimension and the social
      cognitive profile of patients with FM. Relationships between social-cognitive
      abilities and demographic, clinical and psychological variables were also
      investigated. PRINCIPAL FINDINGS: Patients with FM have impairments both in the
      regulation of their own affect and in the recognition of other's emotions, as
      well as in representing other people's mental states. No significant correlations
      were found between social cognition tasks and the subcomponents of the executive
      function that were analysed. CONCLUSIONS: The results show the presence of
      several impairments in social cognition skills in patients with FM, which are
      largely independent of both executive function deficits and symptoms of
      psychological distress. The impairments reported highlight the importance of
      adequately assessing ToM and emotional functioning in clinical practice.

PMID- 25594172
TI  - Skeletal stem cells in space and time.
AB  - The nature, biological characteristics, and contribution to organ physiology of
      skeletal stem cells are not completely determined. Chan et al. and Worthley et
      al. demonstrate that a stem cell for skeletal tissues, and a system of more
      restricted, downstream progenitors, can be identified in mice and demonstrate its
      role in skeletal tissue maintenance and regeneration. 

PMID- 25594173
TI  - Variation in the human immune system is largely driven by non-heritable
      influences.
AB  - There is considerable heterogeneity in immunological parameters between
      individuals, but its sources are largely unknown. To assess the relative
      contribution of heritable versus non-heritable factors, we have performed a
      systems-level analysis of 210 healthy twins between 8 and 82 years of age. We
      measured 204 different parameters, including cell population frequencies,
      cytokine responses, and serum proteins, and found that 77% of these are dominated
      (>50% of variance) and 58% almost completely determined (>80% of variance) by non
      heritable influences. In addition, some of these parameters become more variable
      with age, suggesting the cumulative influence of environmental exposure.
      Similarly, the serological responses to seasonal influenza vaccination are also
      determined largely by non-heritable factors, likely due to repeated exposure to
      different strains. Lastly, in MZ twins discordant for cytomegalovirus infection,
      more than half of all parameters are affected. These results highlight the
      largely reactive and adaptive nature of the immune system in healthy individuals.

PMID- 25594174
TI  - Molecular and genetic properties of tumors associated with local immune cytolytic
      activity.
AB  - How the genomic landscape of a tumor shapes and is shaped by anti-tumor immunity
      has not been systematically explored. Using large-scale genomic data sets of
      solid tissue tumor biopsies, we quantified the cytolytic activity of the local
      immune infiltrate and identified associated properties across 18 tumor types. The
      number of predicted MHC Class I-associated neoantigens was correlated with
      cytolytic activity and was lower than expected in colorectal and other tumors,
      suggesting immune-mediated elimination. We identified recurrently mutated genes
      that showed positive association with cytolytic activity, including beta-2
      microglobulin (B2M), HLA-A, -B and -C and Caspase 8 (CASP8), highlighting loss of
      antigen presentation and blockade of extrinsic apoptosis as key strategies of
      resistance to cytolytic activity. Genetic amplifications were also associated
      with high cytolytic activity, including immunosuppressive factors such as PDL1/2
      and ALOX12B/15B. Our genetic findings thus provide evidence for immunoediting in
      tumors and uncover mechanisms of tumor-intrinsic resistance to cytolytic
      activity. 

PMID- 25594175
TI  - Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome.
AB  - Inflammasomes are involved in diverse inflammatory diseases, so the activation of
      inflammasomes needs to be tightly controlled to prevent excessive inflammation.
      However, the endogenous regulatory mechanisms of inflammasome activation are
      still unclear. Here, we report that the neurotransmitter dopamine (DA) inhibits
      NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). DRD1 signaling
      negatively regulates NLRP3 inflammasome via a second messenger cyclic adenosine
      monophosphate (cAMP), which binds to NLRP3 and promotes its ubiquitination and
      degradation via the E3 ubiquitin ligase MARCH7. Importantly, in vivo data show
      that DA and DRD1 signaling prevent NLRP3 inflammasome-dependent inflammation,
      including neurotoxin-induced neuroinflammation, LPS-induced systemic
      inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation.
      Taken together, our results reveal an endogenous mechanism of inflammasome
      regulation and suggest DRD1 as a potential target for the treatment of NLRP3
      inflammasome-driven diseases. 

PMID- 25594176
TI  - Leptin and insulin act on POMC neurons to promote the browning of white fat.
AB  - The primary task of white adipose tissue (WAT) is the storage of lipids. However,
      "beige" adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the
      energy as heat, but their abundance is diminished in obesity. Stimulating beige
      adipocyte development, or WAT browning, increases energy expenditure and holds
      potential for combating metabolic disease and obesity. Here, we report that
      insulin and leptin act together on hypothalamic neurons to promote WAT browning
      and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin
      and leptin signaling in proopiomelanocortin neurons and prevented diet-induced
      obesity by increasing WAT browning and energy expenditure. The coinfusion of
      insulin plus leptin into the CNS or the activation of proopiomelanocortin neurons
      also increased WAT browning and decreased adiposity. Our findings identify a
      homeostatic mechanism for coordinating the status of energy stores, as relayed by
      insulin and leptin, with the central control of WAT browning. 

PMID- 25594177
TI  - Kynurenic acid is a nutritional cue that enables behavioral plasticity.
AB  - The kynurenine pathway of tryptophan metabolism is involved in the pathogenesis
      of several brain diseases, but its physiological functions remain unclear. We
      report that kynurenic acid, a metabolite in this pathway, functions as a
      regulator of food-dependent behavioral plasticity in C. elegans. The experience
      of fasting in C. elegans alters a variety of behaviors, including feeding rate,
      when food is encountered post-fast. Levels of neurally produced kynurenic acid
      are depleted by fasting, leading to activation of NMDA-receptor-expressing
      interneurons and initiation of a neuropeptide-y-like signaling axis that promotes
      elevated feeding through enhanced serotonin release when animals re-encounter
      food. Upon refeeding, kynurenic acid levels are eventually replenished, ending
      the elevated feeding period. Because tryptophan is an essential amino acid, these
      findings suggest that a physiological role of kynurenic acid is in directly
      linking metabolism to activity of NMDA and serotonergic circuits, which regulate
      a broad range of behaviors and physiologies. 

PMID- 25594178
TI  - A kinase-independent role for EGF receptor in autophagy initiation.
AB  - The epidermal growth factor receptor (EGFR) is upregulated in numerous human
      cancers. Inhibition of EGFR signaling induces autophagy in tumor cells. Here, we
      report an unanticipated role for the inactive EGFR in autophagy initiation.
      Inactive EGFR interacts with the oncoprotein LAPTM4B that is required for the
      endosomal accumulation of EGFR upon serum starvation. Inactive EGFR and LAPTM4B
      stabilize each other at endosomes and recruit the exocyst subcomplex containing
      Sec5. We show that inactive EGFR, LAPTM4B, and the Sec5 subcomplex are required
      for basal and starvation-induced autophagy. LAPTM4B and Sec5 promote EGFR
      association with the autophagy inhibitor Rubicon, which in turn disassociates
      Beclin 1 from Rubicon to initiate autophagy. Thus, the oncoprotein LAPTM4B
      facilitates the role of inactive EGFR in autophagy initiation. This pathway is
      positioned to control tumor metabolism and promote tumor cell survival upon serum
      deprivation or metabolic stress. 

PMID- 25594179
TI  - Pathological axonal death through a MAPK cascade that triggers a local energy
      deficit.
AB  - Axonal death disrupts functional connectivity of neural circuits and is a
      critical feature of many neurodegenerative disorders. Pathological axon
      degeneration often occurs independently of known programmed death pathways, but
      the underlying molecular mechanisms remain largely unknown. Using traumatic
      injury as a model, we systematically investigate mitogen-activated protein kinase
      (MAPK) families and delineate a MAPK cascade that represents the early
      degenerative response to axonal injury. The adaptor protein Sarm1 is required for
      activation of this MAPK cascade, and this Sarm1-MAPK pathway disrupts axonal
      energy homeostasis, leading to ATP depletion before physical breakdown of damaged
      axons. The protective cytoNmnat1/Wld(s) protein inhibits activation of this MAPK
      cascade. Further, MKK4, a key component in the Sarm1-MAPK pathway, is antagonized
      by AKT signaling, which modulates the degenerative response by limiting
      activation of downstream JNK signaling. Our results reveal a regulatory mechanism
      that integrates distinct signals to instruct pathological axon degeneration. 

PMID- 25594180
TI  - Glial lipid droplets and ROS induced by mitochondrial defects promote
      neurodegeneration.
AB  - Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated
      in neurodegenerative disease. Here, we find that a key consequence of ROS and
      neuronal mitochondrial dysfunction is the accumulation of lipid droplets (LD) in
      glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol
      Regulatory Element Binding Protein (SREBP) activity in neurons leading to LD
      accumulation in glia prior to or at the onset of neurodegeneration. The
      accumulated lipids are peroxidated in the presence of ROS. Reducing LD
      accumulation in glia and lipid peroxidation via targeted lipase overexpression
      and/or lowering ROS significantly delays the onset of neurodegeneration.
      Furthermore, a similar pathway leads to glial LD accumulation in Ndufs4 mutant
      mice with neuronal mitochondrial defects, suggesting that LD accumulation
      following mitochondrial dysfunction is an evolutionarily conserved phenomenon,
      and represents an early, transient indicator and promoter of neurodegenerative
      disease. 

PMID- 25594181
TI  - Conformational changes of elongation factor G on the ribosome during tRNA
      translocation.
AB  - The universally conserved GTPase elongation factor G (EF-G) catalyzes the
      translocation of tRNA and mRNA on the ribosome after peptide bond formation.
      Despite numerous studies suggesting that EF-G undergoes extensive conformational
      rearrangements during translocation, high-resolution structures exist for
      essentially only one conformation of EF-G in complex with the ribosome. Here, we
      report four atomic-resolution crystal structures of EF-G bound to the ribosome
      programmed in the pre- and posttranslocational states and to the ribosome trapped
      by the antibiotic dityromycin. We observe a previously unseen conformation of EF
      G in the pretranslocation complex, which is independently captured by dityromycin
      on the ribosome. Our structures provide insights into the conformational space
      that EF-G samples on the ribosome and reveal that tRNA translocation on the
      ribosome is facilitated by a structural transition of EF-G from a compact to an
      elongated conformation, which can be prevented by the antibiotic dityromycin. 

PMID- 25594182
TI  - Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular
      niche.
AB  - Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the
      entire blood system. We generated a highly specific transgenic reporter of HSPCs
      in zebrafish. This allowed us to perform high-resolution live imaging on
      endogenous HSPCs not currently possible in mammalian bone marrow. Using this
      system, we have uncovered distinct interactions between single HSPCs and their
      niche. When an HSPC arrives in the perivascular niche, a group of endothelial
      cells remodel to form a surrounding pocket. This structure appears conserved in
      mouse fetal liver. Correlative light and electron microscopy revealed that
      endothelial cells surround a single HSPC attached to a single mesenchymal stromal
      cell. Live imaging showed that mesenchymal stromal cells anchor HSPCs and orient
      their divisions. A chemical genetic screen found that the compound lycorine
      promotes HSPC-niche interactions during development and ultimately expands the
      stem cell pool into adulthood. Our studies provide evidence for dynamic niche
      interactions upon stem cell colonization. PAPERFLICK: 

PMID- 25594185
TI  - SnapShot: Fanconi anemia and associated proteins.
AB  - Fanconi anemia is a genetic disorder resulting from biallelic mutations in one of
      the 17 FANC genes. It is characterized by congenital abnormalities, bone marrow
      failure, and cancer predisposition. The underlying cause is genomic instability
      resulting from the deficiency in replication-dependent DNA interstrand crosslink
      repair pathway commonly referred to as the Fanconi anemia-BRCA pathway. This
      SnapShot presents the key factors involved. 

PMID- 25594186
TI  - Speciation and determination of bioavailable arsenic species in soil samples by
      one-step solvent extraction and high-performance liquid chromatography with
      inductively coupled plasma mass spectrometry.
AB  - A new analytical method was developed to determine the bioavailable arsenic
      species (arsenite, arsenate, monomethylarsonic acid, and dimethylarsonic acid) in
      soil samples using high-performance liquid chromatography with inductively
      coupled plasma mass spectrometry. Bioavailable arsenic was extracted with
      ammonium phosphate buffer by a simplified one-step solvent extraction procedure.
      To estimate the effect of variables on arsenic extraction, a two-level Plackett
      Burman factorial design was conducted to screen the significant factors that were
      further investigated by a separate univariate approach. The optimum conditions
      were confirmed by compromising the stability of arsenic species and the
      extraction efficiency. The concentration of arsenic species was determined in
      method blank and soil-certified reference materials both spiked with standard
      solutions of arsenic species. All the target arsenic species were stable during
      the whole extraction procedure. Furthermore, the proposed method was applied to
      release bioavailable arsenic from contaminated soil samples, showing that the
      major arsenic species in soil samples were inorganic arsenic: arsenite and
      arsenate, of which the latter was dominant. 

PMID- 25594183
TI  - Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular
      stromal potential.
AB  - The stem cells that maintain and repair the postnatal skeleton remain undefined.
      One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to
      osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the
      existence of these cells has not been proven through fate-mapping experiments. We
      demonstrate here that expression of the bone morphogenetic protein (BMP)
      antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem
      cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts,
      chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem
      cells are concentrated within the metaphysis of long bones not in the
      perisinusoidal space and are needed for bone development, bone remodeling, and
      fracture repair. Grem1 expression also identifies intestinal reticular stem cells
      (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal
      sheath. Grem1 expression identifies distinct connective tissue stem cells in both
      the bone (OCR stem cells) and the intestine (iRSCs). 

PMID- 25594188
TI  - Dopamine in the brain.

PMID- 25594184
TI  - Identification and specification of the mouse skeletal stem cell.
AB  - How are skeletal tissues derived from skeletal stem cells? Here, we map bone,
      cartilage, and stromal development from a population of highly pure, postnatal
      skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream
      progenitors of bone, cartilage, and stromal tissue. We then investigated the
      transcriptome of the stem/progenitor cells for unique gene-expression patterns
      that would indicate potential regulators of mSSC lineage commitment. We
      demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and
      several specific combinations of recombinant mSSC niche factors can activate mSSC
      genetic programs in situ, even in nonskeletal tissues, resulting in de novo
      formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation
      with soluble factors and subsequently regulating the mSSC niche to specify its
      differentiation toward bone, cartilage, or stromal cells could represent a
      paradigm shift in the therapeutic regeneration of skeletal tissues. 

PMID- 25594187
TI  - Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer
      liver metastases is associated with vascular structures.
AB  - Metastatic growth by colorectal cancer cells in the liver requires the ability of
      the cancer cells to interact with the new microenvironment. This interaction
      results in three histological growth patterns of liver metastases: desmoplastic,
      pushing, and replacement. In primary colorectal cancer several proteases,
      involved in the degradation of extracellular matrix components, are up-regulated.
      In liver metastases, their expression is growth pattern dependent. Tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1) is a strong prognostic marker in
      plasma from colorectal cancer patients, with significant higher levels in
      patients with metastatic disease. We therefore wanted to determine the expression
      pattern of TIMP-1 in primary colorectal cancers and their matching liver
      metastases. TIMP-1 mRNA was primarily seen in alpha-smooth-muscle actin (alpha
      SMA)-positive cells. In all primary tumors and liver metastases with desmoplastic
      growth pattern, TIMP-1 mRNA was primarily found in alpha-SMA-positive
      myofibroblasts located at the invasive front. Some alpha-SMA-positive cells with
      TIMP-1 mRNA were located adjacent to CD34-positive endothelial cells, identifying
      them as pericytes. This indicates that TIMP-1 in primary tumors and liver
      metastases with desmoplastic growth pattern has dual functions; being an MMP
      inhibitor at the cancer periphery and involved in tumor-induced angiogenesis in
      the pericytes. In the liver metastases with pushing or replacement growth
      patterns, TIMP-1 was primarily expressed by activated hepatic stellate cells at
      the metastasis/liver parenchyma interface. These cells were located adjacent to
      CD34-positive endothelial cells, suggesting a function in tumor-induced
      angiogenesis. We therefore conclude that TIMP-1 expression is growth pattern
      dependent in colorectal cancer liver metastases.

PMID- 25594189
TI  - Altered response of pendrin-positive intercalated cells in the kidney of Hoxb7
      Cre;Mib1f/f mice.
AB  - The anion exchanger pendrin is exclusively expressed by non-type A intercalated
      cells (ICs), type B ICs and non A-non B ICs. Pendrin-positive ICs are mainly
      localized in the cortical collecting duct (CCD) and connecting tubule (CNT)
      rather than the outer medullary collecting duct (OMCD). Our previous study
      reported that Notch signaling is required for the specification of ureteric bud
      cells to the principal cells (PCs) and ICs in the medullary collecting duct. The
      purpose of this study was to determine whether the deletion of Mind bomb-1
      (Mib1), an E3 ubiquitin ligase required for the initiation of Notch signaling,
      would affect the differentiation of pendrin-positive type B and non A-non B ICs
      in Hoxb7-Cre;Mib1f/f mice. In Hoxb7-Cre;Mib1f/f mice, there was a significant
      increase in the fraction of pendrin-negative/AE1-positive type A ICs not only in
      the OMCD (67.02+/-2.04% vs. 33.78+/-0.71%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) but
      also in the CCD (23.70+/-2.68% vs. 19.71+/-0.43%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f)
      and CNT (23.70+/-2.68% vs. 19.71+/-0.43%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) as
      compared with Mib1f/f. In contrast, there were no significant differences in the
      fraction of pendrin-positive type B ICs (7.11+/-3.84% vs. 7.61+/-4.45%; Hoxb7
      Cre;Mib1f/f vs. Mib1f/f) between the two groups in the cortex including CCD and
      CNT. Furthermore, there was a significant decrease in the fraction of non A-non B
      ICs (8.95+/-2.28% vs. 13.06+/-4.81%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) in these
      tubules in the Hoxb7-Cre;Mib1f/f mice. These results suggest that the degree of
      differentiation of subtypes of ICs may vary depending on the Notch signaling
      pathway. 

PMID- 25594190
TI  - Comparison of multislice computed tomography findings between bicuspid and
      tricuspid aortic valves before and after transcatheter aortic valve implantation.
AB  - AIMS: This study sought to compare the multislice computed tomography (MSCT)
      characteristics of bicuspid aortic valves (BAV) and tricuspid aortic valves (TAV)
      before and after implantation of the CoreValve (Medtronic, Santa Rosa,
      California) or the Edwards SapienXT (Edwards Lifesciences, Irvine, CA). METHODS
      AND RESULTS: From March 2009 to March 2013, a total of 67 TAVI patients who had
      both pre- and post-procedural MSCT were studied. Eleven patients underwent TAVI
      in BAV with the CoreValve (n = 6) or SapienXT (n = 5) and 56 patients underwent
      TAVI in TAV with the CoreValve (n = 38) or SapienXT (n = 18). The BAV group was
      similar to the TAV group except for a higher pre-procedural mean pressure
      gradient (53.1 +/- 17.4 vs. 48.8 +/- 20.4 mm Hg, P = 0.03), a larger annulus
      perimeter (89.3 +/- 9.0 vs. 81.8 +/- 8.1 mm, P = 0.03) and a higher aortic valve
      calcium volume (1262.7 +/- 396.0 vs. 556.4 +/- 461.9 mm(3) , P < 0.01). In the
      CoreValve group, post-procedural mean pressure gradient was significantly higher
      in the BAV group (11.0 +/- 2.6 vs. 8.2 +/- 2.8 mm Hg, P = 0.04) and a smaller
      valve area/pre-annulus area ratio was observed at each level of the prosthesis
      (base of the stent frame 81.7% +/- 14.9% vs. 94.7% +/- 15.0%, P = 0.06, annulus
      level 74.3% +/- 16.7% vs. 89.9% +/- 10.5%, P = 0.03, leaflet level 64.6% +/-
      13.1% vs. 81.2% +/- 13.2%, P < 0.01). This was not observed in the Edwards group.
      CONCLUSIONS: Compared to TAV, patients with BAV have higher gradients, larger
      annulus perimeters and more calcified valves. Higher post procedural gradient and
      valve underexpansion were frequently observed after CoreValve implantation.
      Further MSCT study is required to demonstrate the efficacy of TAVI in BAV.

PMID- 25594192
TI  - Journal club: 5-aminolevulinic acid-derived tumor fluorescence: the diagnostic
      accuracy of visible fluorescence qualities as corroborated by spectrometry and
      histology and postoperative imaging.

PMID- 25594191
TI  - Factors predicting recurrence after resection of clival chordoma using variable
      surgical approaches and radiation modalities.
AB  - BACKGROUND: Clival chordomas frequently recur because of their location and
      invasiveness. OBJECTIVE: To investigate clinical, operative, and anatomic factors
      associated with clival chordoma recurrence. METHODS: Retrospective review of
      clival chordomas treated at our center from 1993 to 2013. RESULTS: Fifty patients
      (56% male) with median age of 59 years (range, 8-76) were newly diagnosed with
      clival chordoma of mean diameter 3.3 cm (range, 1.5-6.7). Symptoms included
      headaches (38%), diplopia (36%), and dysphagia (14%). Procedures included
      transsphenoidal (n=34), transoral (n=4), craniotomy (n=5), and staged approaches
      (n=7). Gross total resection (GTR) rate was 52%, with 83% mean volumetric
      reduction, values that improved over time. While the lower third of the clivus
      was the least likely superoinferior zone to contain tumor (upper third=72%/middle
      third=82%/lower third=42%), it most frequently contained residual tumor (upper
      third=33%/middle third=38%/lower third=63%; P<.05). Symptom improvement rates
      were 61% (diplopia) and 53% (headache). Postoperative radiation included proton
      beam (n=19), cyberknife (n=7), intensity-modulated radiation therapy (n=6),
      external beam (n=10), and none (n=4). At last follow-up of 47 patients, 23 (49%)
      remain disease-free or have stable residual tumor. Lower third of clivus
      progressed most after GTR (upper/mid/lower third=32%/41%/75%). In a multivariate
      Cox proportional hazards model, male gender (hazard ratio [HR]=1.2/P=.03),
      subtotal resection (HR=5.0/P=.02), and the preoperative presence of tumor in the
      middle third (HR=1.2/P=.02) and lower third (HR=1.8/P=.02) of the clivus
      increased further growth or regrowth, while radiation modality did not.
      CONCLUSION: Our findings underscore long-standing support for GTR as reducing
      chordoma recurrence. The lower third of the clivus frequently harbored residual
      or recurrent tumor, despite staged approaches providing mediolateral
      (transcranial+endonasal) or superoinferior (endonasal+transoral) breadth. There
      was no benefit of proton-based over photon-based radiation, contradicting
      conventional presumptions.

PMID- 25594193
TI  - Response to journal club: 5-aminolevulinic acid-derived tumor fluorescence: the
      diagnostic accuracy of visible fluorescence qualities as corroborated by
      spectrometry and histology and postoperative imaging.

PMID- 25594195
TI  - It's all in your head: context-dependent cortical pain processing in the
      orbitofrontal cortex.

PMID- 25594196
TI  - A novel vehicle for the delivery of exogenous neurotrophic factors in spinal cord
      injury.

PMID- 25594197
TI  - Therapeutic cortical-cortical coupling in Parkinson disease.

PMID- 25594198
TI  - Long-term potentiation of pain "memory" in the spinal cord.

PMID- 25594199
TI  - Repurposing mebendazole for the treatment of medulloblastoma.

PMID- 25594200
TI  - Defining the role of epidural steroid injections in the treatment of radicular
      pain from degenerative cervical disk disease.

PMID- 25594201
TI  - Long-term follow-up of the International Subarachnoid-Hemorrhage Aneurysm Trial.

PMID- 25594202
TI  - Mammalian target of rapamycin (mTOR) activity promotes neuronal survival in
      stroke with or without ischemic postconditioning.

PMID- 25594203
TI  - A previously unidentified mechanism of immune evasion in glioblastoma.

PMID- 25594206
TI  - Strength, Static Balance, Physical Activity, and Age Predict Maximal Gait Speed
      in Healthy Older Adults From a Rural Community: A Cross-Sectional Study.
AB  - PURPOSE: Gait speed is related to physical function in older adults. This cross
      sectional study examined the best predictors of maximal gait speed (MGS) among
      physical abilities, and general factors in healthy, rural community-dwelling
      older adults. METHODS: MGS, muscle strength, and postural sway were measured in
      55 community-dwelling participants (age, 72.1 +/- 6.8, range 61-87 years; 72.7%
      women). Two stepwise regressions were used to find MGS predictors in two models:
      physical abilities and global. RESULTS: Strength of knee extensors with 60
      degrees  of knee flexion (KStrength60 degrees ) and maximal distance in the
      anterior-posterior direction with eyes closed explained 50.2% of MGS variance (p
      < .05) in the physical abilities model. KStrength60 degrees , age, and level of
      physical activity explained 63.9% of MGS variance (p < .05) in the global model.
      CONCLUSIONS: Regardless of the model, KStrength60 degrees  was the best predictor
      of MGS in rural female older adults. Future research should examine the
      generalization of these findings to rural male older adults.

PMID- 25594207
TI  - Perpetually perplexing pediatric patients: it's complicated: part 2.
AB  - Many pediatric patients that you encounter will challenge your diagnostic and
      therapeutic skills. As the following cases will illustrate, some will perplex you
      with their esoteric or convoluted illnesses despite your best attempts. Although
      their initial presentation may often be mundane, thorough history taking and
      physical examination, and a keen "clinical intuition" will be invaluable.

PMID- 25594208
TI  - Synthesis, structure and study of azo-hydrazone tautomeric equilibrium of 1,3
      dimethyl-5-(arylazo)-6-amino-uracil derivatives.
AB  - Azo dyes, 1,3-dimethyl-5-(arylazo)-6-aminouracil (aryl=-C6H5 (1), -p-CH3C6H4 (2),
      -p-ClC6H4 (3), -p-NO2C6H4 (4)) were prepared and characterized by UV-vis, FT-IR,
      1H NMR, 13C NMR spectroscopic techniques and single crystal X-ray
      crystallographic analysis. In the light of spectroscopic analysis it evidences
      that of the tautomeric forms, the azo-enamine-keto (A) form is the predominant
      form in the solid state whereas in different solvents it is the hydrazone-imine
      keto (B) form. The study also reveals that the hydrazone-imine-keto (B) form
      exists in an equilibrium mixture with its anionic form in various organic
      solvents. The solvatochromic and photophysical properties of the dyes in various
      solvents with different hydrogen bonding parameter were investigated. The dyes
      exhibit positive solvatochromic property on moving from polar protic to polar
      aprotic solvents. They are fluorescent active molecules and exhibit high intense
      fluorescent peak in some solvents like DMSO and DMF. It has been demonstrated
      that the anionic form of the hydrazone-imine form is responsible for the high
      intense fluorescent peak. In addition, the acid-base equilibrium in between
      neutral and anionic form of hydrazone-imine form in buffer solution of varying pH
      was investigated and evaluated the pKa values of the dyes by making the use of UV
      vis spectroscopic methods. The determined acid dissociation constant (pKa) values
      increase according to the sequence of 2>1>3>4.

PMID- 25594209
TI  - Effect of radiation on cytotoxicity, apoptosis and cell cycle arrest of human
      osteosarcoma MG-63 induced by a ruthenium(II) complex.
AB  - Radiation has large influence on the cytotoxicity, apoptosis and cell cycle
      arrest. The bioactivity of ruthenium(II) complex [Ru(dmb)2(DBHIP)](ClO4)2 (Ru1)
      (DBHIP=2-(3,5-dibromo-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) was
      investigated in the absence and presence of radiation. The cytotoxicity of Ru1
      against MG-63 cells was evaluated by CCK-8 method. Ru1 shows high cytotoxicity
      upon radiation. Radiation can enhance the cytotoxicity of Ru1 on MG-63 cells. The
      apoptosis was studied by Hoechst 33258 staining method and flow cytometry. The
      reactive oxygen species, mitochondrial membrane potential, cell cycle arrest and
      western blot analysis were investigated in detail. The complex induces the
      apoptosis in MG-63 cells through ROS-mediated mitochondrial dysfunction pathway. 

PMID- 25594210
TI  - Determination of L-thyroxine in pharmaceutical preparations by flow injection
      analysis with chemiluminescence detection based on the enhancement of the luminol
      KMnO4 reaction in a micellar medium.
AB  - A novel flow injection chemiluminescence (CL) method for the determination of L
      thyroxine in the presence of cethyltrimethylammonium bromide (CTMAB) surfactant
      micelles is developed. The method is based on the significant signal enhancement
      of L-thyroxine on the luminol-KMnO4 system in alkaline solution sensitized by
      CTMAB. Parameters affecting the reproducibility and CL detection were optimized
      systematically. Under the optimum conditions, the net CL intensity versus L
      thyroxine concentration was linear in the range of 5.0*10(-8)-3.0*10(-6) mol/L
      with the detection limit of 8.9*10(-9) mol/L. The sample throughput is calculated
      to be 140 samples/h and the relative standard deviations (RSDs) for 13 replicate
      determination of 1.0*10(-6) L-thyroxine is 1.1%. The proposed method was
      successfully applied for the determination of L-thyroxine in pharmaceutical
      preparations with satisfactory recoveries in the range of 93.9-105.2%. This
      rapid, sensitive, and high throughput method would provide a new tool for L
      thyroxine analysis.

PMID- 25594211
TI  - A comparative study of smart spectrophotometric methods for simultaneous
      determination of a skeletal muscle relaxant and an analgesic in combined dosage
      form.
AB  - Six simple, specific, accurate and precise spectrophotometric methods were
      developed and validated for the simultaneous determination of the analgesic drug;
      paracetamol (PARA) and the skeletal muscle relaxant; dantrolene sodium (DANT).
      Three methods are manipulating ratio spectra namely; ratio difference (RD), ratio
      subtraction (RS) and mean centering (MC). The other three methods are utilizing
      the isoabsorptive point either at zero order namely; absorbance ratio (AR) and
      absorbance subtraction (AS) or at ratio spectrum namely; amplitude modulation
      (AM). The proposed spectrophotometric procedures do not require any preliminary
      separation step. The accuracy, precision and linearity ranges of the proposed
      methods were determined. The selectivity of the developed methods was
      investigated by analyzing laboratory prepared mixtures of the drugs and their
      combined dosage form. Standard deviation values are less than 1.5 in the assay of
      raw materials and capsules. The obtained results were statistically compared with
      each other and with those of reported spectrophotometric ones. The comparison
      showed that there is no significant difference between the proposed methods and
      the reported methods regarding both accuracy and precision. 

PMID- 25594212
TI  - Synthesis, spectral investigation and catalytic aspects of entrapped VO(IV) and
      Cu(II) complexes into the supercages of zeolite-Y.
AB  - VO(IV) and Cu(II) complexes with Schiff base ligand derived from 1-phenyl-3
      methyl-4-formyl-2-pyrazolin-5-one (PMFP) and 2-amino phenol have been synthesized
      as their neat and entrapped complexes into the supercages of zeolite-Y. The
      compounds were characterized by chemical analysis (ICP-OES and elemental),
      electronic and/or UV reflectance spectra, FTIR spectroscopy, X-ray powder
      diffraction patterns, SEMs, BET and thermogravimetric (TG) analysis. All the
      prepared catalysts were tested on the liquid phase limonene oxidation reaction,
      using 30% H2O2 as an oxidant. Limonene glycol, carveol, carvone and limonene 1,2
      epoxide were the main products obtained. It was observed that zeolite-Y entrapped
      complexes exhibited higher catalytic activity than neat complexes. The catalysts
      undergo no metal leaching and can be easily recovered and reused. The use of
      inexpensive catalyst and oxidant are significant practical advantages of this
      environmentally friendly process. 

PMID- 25594213
TI  - Investigation on the photophysical properties of ESPT inspired salicylaldehyde
      based sensor for fluoride sensing.
AB  - A simple, highly selective and sensitive chemosensor (E)-2-((quinolin-8-ylimino)
      methyl) phenol (QP) has been developed for the fluoride, as demonstrated by the
      photophysical properties obtained by UV-vis and fluorescent methods. Excited
      state inter/intramolecular proton transfer (ESPT) was suggested to be responsible
      for the fluoride-induced 'turn on' fluorescence and the blue shift of 25 nm in
      the emission spectrum.

PMID- 25594214
TI  - Mean centering of ratio spectra and concentration augmented classical least
      squares in a comparative approach for quantitation of spectrally overlapped bands
      of antihypertensives in formulations.
AB  - Two different methods manipulating spectrophotometric data have been developed,
      validated and compared. One is capable of removing the signal of any interfering
      components at the selected wavelength of the component of interest (univariate).
      The other includes more variables and extracts maximum information to determine
      the component of interest in the presence of other components (multivariate). The
      applied methods are smart, simple, accurate, sensitive, precise and capable of
      determination of spectrally overlapped antihypertensives; hydrochlorothiazide
      (HCT), irbesartan (IRB) and candesartan (CAN). Mean centering of ratio spectra
      (MCR) and concentration residual augmented classical least-squares method
      (CRACLS) were developed and their efficiency was compared. CRACLS is a simple
      method that is capable of extracting the pure spectral profiles of each component
      in a mixture. Correlation was calculated between the estimated and pure spectra
      and was found to be 0.9998, 0.9987 and 0.9992 for HCT, IRB and CAN, respectively.
      The methods were successfully determined the three components in bulk powder,
      laboratory-prepared mixtures, and combined dosage forms. The results obtained
      were compared statistically with each other and to those of the official methods.

PMID- 25594215
TI  - Birth Weight, Insulin Resistance, and Blood Pressure in Late Preterm Infants.
AB  - OBJECTIVES: This study aims to compare insulin sensitivity, lipid profile, and
      blood pressure in late preterm infants born at appropriate for gestational age
      (AGA) and small for gestational age (SGA). STUDY DESIGN: We conducted a
      prospective, observational study on AGA and SGA late preterm infants. Blood
      pressure, fasting blood glucose, insulin, insulin-like growth factor 1 (IGF-1),
      insulin resistance, and lipid profile were measured on the 1st day and in the 2nd
      week of life. RESULTS: Overall 81 infants (41 AGA and 40 SGA) were included in
      the study. At the time of enrollment, there was no difference in blood pressure,
      insulin resistance, and lipid profile. At follow-up SGA patients had
      significantly decreased diastolic blood pressure (48 +/- 11 mm Hg vs. 42 +/- 11
      mm Hg, p = 0.04), and decreased IGF-1 (139 ng/mL [119-153] vs. 124 ng/mL [115
      138], p = 0.05). No linear association was found between the insulin resistance
      and either birth weight percentile, day of life, or average 1st week daily
      caloric intake. CONCLUSION:  As compared with AGA, SGA late preterm infants had
      lower diastolic blood pressure and lower IGF-1 during the 2nd week of life, but
      similar insulin resistance and lipid profile. We speculate that although
      metabolic derangements in SGA infants could have occurred at a much earlier age
      in fetal life, their manifestations may not be present in the immediate postnatal
      life.

PMID- 25594216
TI  - Establishing thromboelastography with platelet-function analyzer reference ranges
      and other measures in healthy term pregnant women.
AB  - OBJECTIVE: The diagnosis of coagulopathy cannot always be performed at point of
      care. Thromboelastography (TEG) and the platelet-function analyzer (PFA-100),
      have emerged as reliable means for coagulation analysis. However, their reliable
      utility in pregnancy remains to be determined. We sought to establish reference
      values with concomitant determination of other known coagulation measures in
      nonlaboring gravidae in an effort to report the mean and variance of multiple
      testing modalities. STUDY DESIGN: Fifty-nine term, nonlaboring, pregnant women
      without comorbidities were enrolled, either at presentation for scheduled
      delivery or at presentation to triage for a non-labor-related indication. TEG,
      PFA-100, and complete coagulation measures of the overall hemostatic function
      (including prothrombin time, activated partial thromboplastin time, fibrinogen,
      protein C, protein S, von Willebrand factor antigen, ristocetin cofactor
      activity, and ADAMTS-13) were performed. Prior investigations of TEG and PFA-100
      parameters in normal gravidae were reviewed, and pooled means and standard
      deviations (as a measure of variance) were calculated. RESULTS: TEG and PFA-100
      parameters were significantly different among pregnant gravidae compared with
      nonpregnant reference ranges, and varied in association with other measures of
      the coagulation system. Our results and the pooled results reflect a
      hypercoagulable state. CONCLUSION: Our data suggest that TEG values are
      significantly different in term, nonlaboring, healthy gravidae compared with
      nonpregnant reference values. Pooled means and standard deviations shown here may
      be considered for reference.

PMID- 25594217
TI  - Rifampin use and safety in hospitalized infants.
AB  - OBJECTIVE: This study aims to examine the use and safety of rifampin in the
      hospitalized infants. STUDY DESIGN: Observational study of clinical and
      laboratory adverse events among infants exposed to rifampin from 348 neonatal
      intensive care units managed by the Pediatrix Medical Group between 1997 and
      2012. RESULT: Overall, 2,500 infants received 4,279 courses of rifampin; mean
      gestational age was 27 weeks (5th, 95th percentile; 23, 36) and mean birth weight
      was 1,125 g (515; 2,830). Thrombocytopenia (121/1,000 infant days) and conjugated
      hyperbilirubinemia (25/1,000 infant days) were the most common laboratory adverse
      events. The most common clinical adverse events were medical necrotizing
      enterocolitis (64/2,500 infants, 3%) and seizure (60/2,500 infants, 2%).
      CONCLUSION: The overall incidence of adverse events among infants receiving
      rifampin appears low; however, additional studies to further evaluate safety and
      dosing of rifampin in this population are needed.

PMID- 25594219
TI  - Case Volume and Outcomes of Congenital Diaphragmatic Hernia Surgery in Academic
      Medical Centers.
AB  - OBJECTIVE: The outcome of patients with congenital diaphragmatic hernia (CDH) has
      not improved in the last decade and surgical repair remains the mainstay of
      treatment. The purpose of the present study was to assess whether a volume
      outcome relationship exists in the U.S. academic medical centers performing
      surgical repair of neonatal CDH. STUDY DESIGN: A retrospective cross-sectional
      analysis of discharge data for neonates undergoing CDH repair in academic medical
      center members of the University Health-System Consortium was employed.
      Unadjusted mortality was compared between lower and higher surgical volume
      centers. A binary logistic regression model was fit to test the relationship of
      surgical volume with mortality. RESULTS: A total of 3,738 patients underwent
      surgical repair in 122 unique academic medical centers in the United States. The
      overall rate of survival was 75.2%. There was no difference in unadjusted
      mortality between lower and higher volume centers. After controlling for patient
      and hospital variables, there was no difference in the odds of mortality between
      lower and higher volume centers (odds ratio 1.03 [95% confidence interval, 0.86
      1.23, p = 0.730]). CONCLUSIONS: Neonates born with congenital diaphragmatic
      hernia can undergo surgical repair in the U.S. academic medical centers
      independent of center procedure volume and expect good surgical outcomes.

PMID- 25594218
TI  - Risk Factors for Prolonged Postpartum Length of Stay Following Cesarean Delivery.
AB  - OBJECTIVE: This study aims to identify risk factors for prolonged postpartum
      length of stays (LOS) after cesarean delivery (CD). STUDY DESIGN: Patients
      undergoing CD were sourced from a multicenter registry of 19 academic centers
      between 1999 and 2002 (n = 57,067). Prolonged postpartum LOS was defined as a
      hospitalization duration >= 90th centile. Maternal, antepartum, perioperative,
      and neonatal variables were compared between women with and without prolonged
      postpartum LOS. RESULTS: The 90th centile for postpartum LOS was 4 days, with
      14,954 women experiencing prolonged postpartum LOS. Women with perioperative
      complications had the highest independent risk for a prolonged postpartum LOS:
      ileus (adjusted odds ratio [aOR] = 12.28; 95% confidence interval CI = 8.98
      16.8); endometritis (aOR = 10.45; 95% CI = 9.51-11.5), and wound complications
      (aOR = 5.49; 95% CI = 4.54-6.63). Several antepartum, perioperative, and neonatal
      variables were associated with a prolonged postpartum LOS. CONCLUSION:
      Perioperative complications had the highest risk for prolonged LOS after CD.
      Strategies to reduce perioperative complications are needed to decrease the
      health care burden of prolonged post-CD LOS.

PMID- 25594220
TI  - Comparison of the Miller Laryngoscope and Videolaryngoscope for Tracheal
      Intubation by Novice Doctors during Neonatal Cardiopulmonary Resuscitation: A
      Randomized Crossover Simulation Trial.
AB  - OBJECTIVE: Recent guidelines for neonatal cardiopulmonary resuscitation emphasize
      the importance of adequate ventilation. In cases of failed resuscitation with
      positive pressure ventilation, tracheal intubation and chest compressions are
      recommended. The present study compared the utility of the Miller laryngoscope
      (Mil) and the videolaryngoscope Pentax-AWS Airway Scope (AWS; Hoya, Tokyo, Japan)
      with an infant or neonatal-sized Intlock (AWS-N; Pentax) during chest
      compressions on a neonatal manikin. STUDY DESIGN: A total of 23 novice doctors
      performed tracheal intubation on a neonatal manikin using the Mil and AWS-N, with
      or without chest compressions. RESULTS: In the Mil trials, all participants
      secured the airway without chest compressions, but nine failed with compressions
      (p < 0.001). In AWS-N trials, all participants succeeded regardless of whether
      chest compressions were performed or not. Intubation time was significantly
      longer with chest compressions with the Mil (p < 0.001), but not with the AWS-N.
      Laryngoscopy difficulty, as assessed by a visual analog scale (VAS), increased
      significantly with chest compressions with the Mil, but not with the AWS-N, while
      the VAS for tube passage through the glottis increased with compressions with the
      Mil, but not with the AWS-N. CONCLUSION: The AWS-N is an effective device for
      endotracheal intubation during chest compressions in neonatal simulations
      performed by novice doctors.

PMID- 25594221
TI  - Does near-infrared spectroscopy identify asphyxiated newborns at risk of
      developing brain injury during hypothermia treatment?
AB  - OBJECTIVE: The aim of this article is to assess whether near-infrared
      spectroscopy (NIRS) identifies, during hypothermia treatment, the asphyxiated
      newborns who later develop brain injury. STUDY DESIGN: In this study, asphyxiated
      newborns, for whom later brain injury was defined by brain imaging and/or autopsy
      results, were monitored by NIRS during therapeutic hypothermia. We compared
      regional cerebral oxygenation saturation (rSO2) measured by NIRS at key time
      points for newborns who developed or did not develop later brain injury. RESULTS:
      A total of 18 asphyxiated newborns treated with hypothermia were enrolled. rSO2
      was higher in the asphyxiated newborns who developed later brain injury.
      Sensitivity within the first 10 hours of hypothermia treatment for an adverse
      outcome was 100% (95% confidence interval [CI], 70-100%) and specificity was 83%
      (95% CI, 36-99%). CONCLUSIONS: NIRS appears to identify asphyxiated newborns at
      risk of developing brain injury as early as the first 10 hours of hypothermia
      treatment. Thus, NIRS may have an important role as an early outcome predictor in
      this population.

PMID- 25594223
TI  - Glycosylated enfuvirtide: a long-lasting glycopeptide with potent anti-HIV
      activity.
AB  - Many peptide-based therapeutics have short circulatory half-lives. We report here
      that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be
      dramatically improved by a chemical glycosylation approach. A set of glycosylated
      ENFs with varying glycosylation sites and glycan structures were synthesized.
      Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold
      extended half-life in rats relative to ENF (T1/2: 23.1 vs 1.5 h), and its
      antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound
      to a functional fragment of the HIV fusogenic protein gp41 and formed complexes
      with high affinity and alpha-helicity, revealing the mechanism behind its potent
      antiviral activity. Because it is widely accepted in biology that glycosylation
      protects proteins from denaturation and proteases, our approach may be useful for
      the development of novel protein and peptide drugs with enhanced pharmaceutical
      properties. 

PMID- 25594224
TI  - An effective approach for alleviating cation-induced backbone degradation in
      aromatic ether-based alkaline polymer electrolytes.
AB  - Aromatic ether-based alkaline polymer electrolytes (APEs) are one of the most
      popular types of APEs being used in fuel cells. However, recent studies have
      demonstrated that upon being grafted by proximal cations some polar groups in the
      backbone of such APEs can be attacked by OH(-), leading to backbone degradation
      in an alkaline environment. To resolve this issue, we performed a systematic
      study on six APEs. We first replaced the polysulfone (PS) backbone with
      polyphenylsulfone (PPSU) and polyphenylether (PPO), whose molecular structures
      contain fewer polar groups. Although improved stability was seen after this
      change, cation-induced degradation was still obvious. Thus, our second move was
      to replace the ordinary quaternary ammonia (QA) cation, which had been closely
      attached to the polymer backbone, with a pendant-type QA (pQA), which was linked
      to the backbone through a long side chain. After a stability test in a 1 mol/L
      KOH solution at 80  degrees C for 30 days, all pQA-type APEs (pQAPS, pQAPPSU, and
      pQAPPO) exhibited as low as 8 wt % weight loss, which is close to the level of
      the bare backbone (5 wt %) and remarkably lower than those of the QA-type APEs
      (QAPS, QAPPSU, and QAPPO), whose weight losses under the same conditions were
      >30%. The pQA-type APEs also possessed clear microphase segregation morphology,
      which led to ionic conductivities that were higher, and water uptakes and degrees
      of membrane swelling that were lower, than those of the QA-type APEs. These
      observations unambiguously indicate that designing pendant-type cations is an
      effective approach to increasing the chemical stability of aromatic ether-based
      APEs. 

PMID- 25594225
TI  - Orthogonal Fatty Acid Biosynthetic Pathway Improves Fatty Acid Ethyl Ester
      Production in Saccharomyces cerevisiae.
AB  - Fatty acid ethyl esters (FAEEs) are a form of biodiesel that can be microbially
      produced via a transesterification reaction of fatty acids with ethanol. The
      titer of microbially produced FAEEs can be greatly reduced by unbalanced
      metabolism and an insufficient supply of fatty acids, resulting in a commercially
      inviable process. Here, we report on a pathway engineering strategy in
      Saccharomyces cerevisiae for enhancing the titer of microbially produced FAEEs by
      providing the cells with an orthogonal route for fatty acid synthesis. The fatty
      acids generated from this heterologous pathway would supply the FAEE production,
      safeguarding endogenous fatty acids for cellular metabolism and growth. We
      investigated the heterologous expression of a Type-I fatty acid synthase (FAS)
      from Brevibacterium ammoniagenes coupled with WS/DGAT, the wax ester
      synthase/acyl-coenzyme that catalyzes the transesterification reaction with
      ethanol. Strains harboring the orthologous fatty acid synthesis yielded a 6.3
      fold increase in FAEE titer compared to strains without the heterologous FAS.
      Variations in fatty acid chain length and degree of saturation can affect the
      quality of the biodiesel; therefore, we also investigated the diversity of the
      fatty acid production profile of FAS enzymes from other Actinomyces organisms. 

PMID- 25594226
TI  - Metabolomic assessment reveals an elevated level of glucosinolate content in
      CaCl2 treated broccoli microgreens.
AB  - Preharvest calcium application has been shown to increase broccoli microgreen
      yield and extend shelf life. In this study, we investigated the effect of calcium
      application on its metabolome using ultra-high-performance liquid chromatography
      with mass spectrometry. The data collected were analyzed using principal
      component analysis and orthogonal projection to latent structural discriminate
      analysis. Chemical composition comparison shows that glucosinolates, a very
      important group of phytochemicals, are the major compounds enhanced by preharvest
      treatment with 10 mM calcium chloride (CaCl2). Aliphatic glucosinolates
      (glucoerucin, glucoiberin, glucoiberverin, glucoraphanin, pentyl glucosinolate,
      and hexyl glucosinolate) and indolic glucosinolates (glucobrassicin,
      neoglucobrassicin, and 4-hydroxyglucobrassicin) were increased significantly in
      the CaCl2 treated microgreens using metabolomic approaches. Targeted
      glucosinolate analysis using the ISO 9167-1 method was further employed to
      confirm the findings. Results indicate that glucosinolates can be considered as a
      class of compounds that are responsible for the difference between two groups and
      a higher glucosinolate level was found in CaCl2 treated groups at each time point
      after harvest in comparison with the control group. 

PMID- 25594227
TI  - Bespoke photoreductants: tungsten arylisocyanides.
AB  - Modular syntheses of oligoarylisocyanide ligands that are derivatives of 2,6
      diisopropylphenyl isocyanide (CNdipp) have been developed; tungsten complexes
      incorporating these oligoarylisocyanide ligands exhibit intense metal-to-ligand
      charge-transfer visible absorptions that are red-shifted and more intense than
      those of the parent W(CNdipp)6 complex. Additionally, these W(CNAr)6 complexes
      have enhanced excited-state properties, including longer lifetimes and very high
      quantum yields. The decay kinetics of electronically excited W(CNAr)6 complexes
      (*W(CNAr)6) show solvent dependences; faster decay is observed in higher
      dielectric solvents. *W(CNAr)6 lifetimes are temperature dependent, suggestive of
      a strong coupling nonradiative decay mechanism that promotes repopulation of the
      ground state. Notably, *W(CNAr)6 complexes are exceptionally strong reductants:
      [W(CNAr)6](+)/*W(CNAr)6 potentials are more negative than -2.7 V vs
      [Cp2Fe](+)/Cp2Fe. 

PMID- 25594228
TI  - Gas phase studies of the Pesci decarboxylation reaction: synthesis, structure,
      and unimolecular and bimolecular reactivity of organometallic ions.
AB  - CONSPECTUS: Decarboxylation chemistry has a rich history, and in more recent
      times, it has been recruited in the quest to develop cheaper, cleaner, and more
      efficient bond-coupling reactions. Thus, over the past two decades, there has
      been intense investigation into new metal-catalyzed reactions of carboxylic
      substrates. Understanding the elementary steps of metal-mediated transformations
      is at the heart of inventing new reactions and improving the performance of
      existing ones. Fortunately, during the same time period, there has been a
      convergence in mass spectrometry (MS) techniques, which allows these catalytic
      processes to be examined efficiently in the gas phase. Thus, electrospray
      ionization (ESI) sources have been combined with ion-trap mass spectrometers,
      which in turn have been modified to either accept radiation from tunable OPO
      lasers for spectroscopy based structural assignment of ions or to allow the study
      of ion-molecule reactions (IMR). The resultant "complete" gas-phase chemical
      laboratories provide a platform to study the elementary steps of metal-catalyzed
      decarboxylation reactions in exquisite detail. In this Account, we illustrate how
      the powerful combination of ion trap mass spectrometry experiments and DFT
      calculations can be systematically used to examine the formation of
      organometallic ions and their chemical transformations. Specifically, ESI-MS
      allows the transfer of inorganic carboxylate complexes, [RCO2M(L)n](x), (x =
      charge) from the condensed to the gas phase. These mass selected ions serve as
      precursors to organometallic ions [RM(L)n](x) via neutral extrusion of CO2,
      accessible by slow heating in the ion trap using collision induced dissociation
      (CID). This approach provides access to an array of organometallic ions with well
      defined stoichiometry. In terms of understanding the decarboxylation process, we
      highlight the role of the metal center (M), the organic group (R), and the
      auxiliary ligand (L), along with cluster nuclearity, in promoting the formation
      of the organometallic ion. Where isomeric organometallic ions are generated and
      normal MS approaches cannot distinguish them, we describe approaches to elucidate
      the decarboxylation mechanism via determination of their structure. These
      "unmasked" organometallic ions, [RM(L)n](x), can also be structurally
      interrogated spectroscopically or via CID. We have thus compared the gas-phase
      structures and decomposition of several highly reactive and synthetically
      important organometallic ions for the first time. Perhaps the most significant
      aspect of this work is the study of bimolecular reactions, which provides
      experimental information on mechanistically obscure bond-formation and cross
      coupling steps and the intrinsic reactivity of ions. We have sought to understand
      transformations of substrates including acid-base and hydrolysis reactions, along
      with reactions resulting in C-C bond formation. Our studies also allow a direct
      comparison of the performance of different metal catalysts in the individual
      elementary steps associated with protodecarboxylation and decarboxylative
      alkylation cycles. Electronic structure (DFT and ab initio) and dynamics (RRKM)
      calculations provide further mechanistic insights into these reactions. The broad
      implications of this research are that new reactions can be discovered and that
      the performance of metal catalysts can be evaluated in terms of each of their
      elementary steps. This has been particularly useful for the study of metal
      mediated decarboxylation reactions.

PMID- 25594229
TI  - Probing combustion chemistry in a miniature shock tube with synchrotron VUV photo
      ionization mass spectrometry.
AB  - Tunable synchrotron-sourced photoionization time-of-flight mass spectrometry (PI
      TOF-MS) is an important technique in combustion chemistry, complementing lab
      scale electron impact and laser photoionization studies for a wide variety of
      reactors, typically at low pressure. For high-temperature and high-pressure
      chemical kinetics studies, the shock tube is the reactor of choice. Extending the
      benefits of shock tube/TOF-MS research to include synchrotron sourced PI-TOF-MS
      required a radical reconception of the shock tube. An automated, miniature, high
      repetition-rate shock tube was developed and can be used to study high-pressure
      reactive systems (T > 600 K, P < 100 bar) behind reflected shock waves. In this
      paper, we present results of a PI-TOF-MS study at the Advanced Light Source at
      Lawrence Berkeley National Laboratory. Dimethyl ether pyrolysis (2% CH3OCH3/Ar)
      was observed behind the reflected shock (1400 < T5 < 1700 K, 3 < P5 < 16 bar)
      with ionization energies between 10 and 13 eV. Individual experiments have
      extremely low signal levels. However, product species and radical intermediates
      are well-resolved when averaging over hundreds of shots, which is ordinarily
      impractical in conventional shock tube studies. The signal levels attained and
      data throughput rates with this technique are comparable to those with other
      synchrotron-based PI-TOF-MS reactors, and it is anticipated that this high
      pressure technique will greatly complement those lower pressure techniques. 

PMID- 25594230
TI  - Rhodium(III)-catalyzed oxidative alkenylation of 1,3-dithiane-protected
      arenecarbaldehydes via regioselective C-H bond cleavage.
AB  - A Rh(III)-catalyzed direct alkenylation of 2-aryl-1,3-dithiane derivatives with
      alkenes has been developed. The 1,3-dithiane group can serve as an effective
      directing group for the exclusively monoselective alkenylation under mild
      oxidative conditions. The directing group is readily removable after the coupling
      event. 

PMID- 25594222
TI  - Is There a Threshold Oral Glucose Tolerance Test Value for Predicting Adverse
      Pregnancy Outcome?
AB  - OBJECTIVE: This study aims to determine whether there is a threshold 3-hour oral
      glucose tolerance test (OGTT) value associated with accelerated risk of adverse
      pregnancy outcomes. STUDY DESIGN: In a secondary analysis of a cohort of women
      with untreated mild gestational glucose intolerance, we used generalized additive
      models with smoothing splines to explore nonlinear associations between each of
      the 3-hour OGTT values (fasting, 1-hour, 2-hour, and 3-hour) and adverse
      pregnancy outcomes, including the study's composite outcome (perinatal mortality,
      hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia, and/or birth
      trauma), large for gestational age birth weight, small for gestational age birth
      weight, shoulder dystocia, neonatal hypoglycemia, gestational hypertension
      (gHTN), and preeclampsia. RESULTS: Among the 1,360 eligible women, each timed
      OGTT value was linearly associated with increased odds of composite adverse
      outcome. We found evidence of a departure from linearity only for the association
      between fasting glucose and gHTN/preeclampsia, with a stronger association for
      values of 85 to 94 mg/dL (p = 0.03). We found no evidence of departure from
      linearity for any other OGTT values and measured outcomes (all chi-square test p
      values >= 0.05). CONCLUSION: In a population of untreated women with mild
      gestational glucose intolerance and fasting OGTT < 95 mg/dL, we found an
      increasing risk of gHTN with a fasting glucose between 85 and 94 mg/dL.

PMID- 25594231
TI  - Impact of Marcellus Shale natural gas development in southwest Pennsylvania on
      volatile organic compound emissions and regional air quality.
AB  - The Marcellus Shale is the largest natural gas deposit in the U.S. and rapid
      development of this resource has raised concerns about regional air pollution. A
      field campaign was conducted in the southwestern Pennsylvania region of the
      Marcellus Shale to investigate the impact of unconventional natural gas (UNG)
      production operations on regional air quality. Whole air samples were collected
      throughout an 8050 km(2) grid surrounding Pittsburgh and analyzed for methane,
      carbon dioxide, and C1-C10 volatile organic compounds (VOCs). Elevated mixing
      ratios of methane and C2-C8 alkanes were observed in areas with the highest
      density of UNG wells. Source apportionment was used to identify characteristic
      emission ratios for UNG sources, and results indicated that UNG emissions were
      responsible for the majority of mixing ratios of C2-C8 alkanes, but accounted for
      a small proportion of alkene and aromatic compounds. The VOC emissions from UNG
      operations accounted for 17 +/- 19% of the regional kinetic hydroxyl radical
      reactivity of nonbiogenic VOCs suggesting that natural gas emissions may affect
      compliance with federal ozone standards. A first approximation of methane
      emissions from the study area of 10.0 +/- 5.2 kg s(-1) provides a baseline for
      determining the efficacy of regulatory emission control efforts. 

PMID- 25594232
TI  - Raman and Mossbauer spectroscopy and X-ray diffractometry studies on quenched
      copper-ferri-aluminates.
AB  - Four spinel ferrite compositions of the CuAl(x)Fe(2-x)O4, x = 0.0, 0.2, 0.4, 0.6,
      system prepared by usual double-sintering ceramic route and quenched (rapid
      thermal cooling) from final sintering temperature (1373 K) to liquid nitrogen
      temperature (80 K) were investigated by employing X-ray powder diffractometry,
      (57)Fe Mossbauer spectroscopy, and micro-Raman spectroscopy at 300 K. The Raman
      spectra collected in the wavenumber range of 100-1000 cm(-1) were analyzed in a
      systematic manner and showed five predicted modes for the spinel structure and
      splitting of A1g Raman mode into two/three energy values, attributed to peaks
      belonging to each ion (Cu(2+), Fe(3+), and Al(3+)) in the tetrahedral positions.
      The suppression of lower-frequency peaks was explained on the basis of weakening
      in magnetic coupling and reduction in ferrimagnetic behavior as well as increase
      in stress induced by square bond formation on Al(3+) substitution. The
      enhancement in intensity, random variation of line width, and blue shift for
      highest frequency peak corresponding to A1g mode were observed. The ferric ion
      (Fe(3+)) concentration for different compositions determined from Raman spectral
      analysis agrees well with that deduced by means of X-ray diffraction line
      intensity calculations and Mossbauer spectral analysis. An attempt was made to
      determine elastic and thermodynamic properties from Raman spectral analysis and
      elastic constants from cation distribution.

PMID- 25594233
TI  - Demethoxycurcumin modulates human P-glycoprotein function via uncompetitive
      inhibition of ATPase hydrolysis activity.
AB  - Curcuminoids are major components of Curcuma longa L., which is widely used as
      spice in food. This study aimed at identifying whether curcumin,
      demethoxycurcumin, and bisdemethoxycurcumin could modulate efflux function of
      human P-glycoprotein and be used as chemosensitizers in cancer treatments.
      Without altering P-glycoprotein expression levels and conformation, the purified
      curcuminoids significantly inhibited P-glycoprotein efflux function. In rhodamine
      123 efflux and calcein-AM accumulation assays, demethoxycurcumin demonstrated the
      highest inhibition potency (inhibitory IC50 = 1.56 +/- 0.13 MUM) among the
      purified curcuminoids, as well as in the fold of reversal assays.
      Demethoxycurcumin inhibited P-glycoprotein-mediated ATP hydrolysis under
      concentrations of <1 MUM and efficiently inhibited 200 MUM verapamil-stimulated
      ATPase activity, indicating a high affinity of demethoxycurcumin for P
      glycoprotein. These results suggested that demethoxycurcumin may be a potential
      additive natural product in combination with chemotherapeutic agents in drug
      resistant cancers. 

PMID- 25594234
TI  - Frequency and causes of C-reactive protein and erythrocyte sedimentation rate
      disagreements in adults.
AB  - AIM: C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are
      often ordered together in patients with suspected infection or inflammation.
      However, the test results can disagree in as many as 33% of patients. Our aim was
      to further examine CRP/ESR disagreements and their stability on repeat testing.
      METHODS: We analyzed simultaneously ordered CRP and ESR results in 70 adult
      patients who had been tested on three separate occasions a median of 4 weeks
      apart. RESULTS: Initial CRP/ESR disagreements occurred in 14 of the 70 patients
      (20%; 95% CI, 12-31). Only four of these 14 patients had stable CRP/ESR
      disagreements throughout the study (two with lupus nephritis and one with
      osteomyelitis had persistent high ESR/normal CRP disagreements and one with
      rheumatoid arthritis had a persistent high CRP/normal ESR disagreement). The
      other 10 patients with initial CRP/ESR disagreements later exhibited CRP/ESR
      agreements. Of the 56 patients with initial CRP/ESR agreements, only 10 developed
      a CRP/ESR disagreement (or disagreements) on subsequent testing. CONCLUSION:
      CRP/ESR disagreements are common in clinical practice. Three mechanisms were
      identified to explain CRP/ESR disagreements: (i) slight fluctuations in the CRP
      and ESR around the upper limits of normal for these tests; (ii) development of an
      intercurrent illness; and (iii) different time courses of CRP and ESR elevations,
      in which the CRP rose and fell faster than the ESR.

PMID- 25594235
TI  - Rigid urea and self-healing thiourea ethanolamine monolayers.
AB  - A series of long-tail alkyl ethanolamine analogs containing amide-, urea-, and
      thiourea moieties was synthesized and the behavior of the corresponding
      monolayers was assessed on the Langmuir-Pockels trough combined with grazing
      incidence X-ray diffraction experiments and complemented by computer simulations.
      All compounds form stable monolayers at the soft air/water interface. The phase
      behavior is dominated by strong intermolecular headgroup hydrogen bond networks.
      While the amide analog forms well-defined monolayer structures, the stronger
      hydrogen bonds in the urea analogs lead to the formation of small three
      dimensional crystallites already during spreading due to concentration
      fluctuations. The hydrogen bonds in the thiourea case form a two-dimensional
      network, which ruptures temporarily during compression and is recovered in a self
      healing process, while in the urea clusters the hydrogen bonds form a more planar
      framework with gliding planes keeping the structure intact during compression.
      Because the thiourea analogs are able to self-heal after rupture, such compounds
      could have interesting properties as tight, ordered, and self-healing monolayers.

PMID- 25594236
TI  - Helping Parents Cope with Suicide Threats: An Approach Based on Nonviolent
      Resistance.
AB  - Parent training in nonviolent resistance was adapted to deal with situations of
      suicide threat by children, adolescents, and young adults. The approach aims at
      reducing the risk potential and the mutual distress surrounding the threat
      interaction. Parent training in nonviolent resistance has been shown to help
      parents move from helplessness to presence, from isolation to connectedness, from
      submission to resistance, from escalation to self-control, and from mutual
      distancing and hostility to care and support. Those emphases can be crucial for
      the diminution of suicide risk. Parents show good ability to implement the
      approach and report gains on various areas over and beyond the reduction in
      suicide threat. A particular advantage is that the method can be used also in
      cases where the young person threatening suicide is not willing to cooperate. 

PMID- 25594237
TI  - Evaluation of Humoral Response and Protective Efficacy of an Inactivated Vaccine
      Against Peste des Petits Ruminants Virus in Goats.
AB  - Four goats were inoculated with an inactivated peste des petits ruminants virus
      (PPRV) vaccine. Three unvaccinated goats were kept as controls. After 36 days,
      the four goats were revaccinated. The immune response was monitored by virus
      neutralization test showing that two doses of the vaccine were able to stimulate
      strong immune response in all the vaccinated animals. The vaccinated goat and the
      controls were challenged with virulent PPRV intranasally. After PPRV challenge,
      the three control goats showed fever, viremia and virus excretion through mucosal
      surfaces, whereas the vaccinated goats were fully protected against PPRV
      infection and replication. 

PMID- 25594238
TI  - Impaired proliferation of pancreatic beta cells, by reduced placental growth
      factor in pre-eclampsia, as a cause for gestational diabetes mellitus.
AB  - OBJECTIVES: Reduced increase in serum placental growth factor (PLGF) levels
      frequently occurs in patients with pre-eclampsia (PE) and thus has been used as a
      predictive factor for developing PE. However, it has remained elusive how
      shortage of PLGF could affect pancreatic endocrine homoeostasis and function in
      pregnancy to lead to development of gestational diabetes mellitus (GDM).
      MATERIALS AND METHODS: We used l-NAME injection in mice, as a model of human PE,
      in which PLGF levels were significantly reduced. RESULTS: We not only confirmed
      reduced serum PLGF levels in patients with PE but also detected strong
      correlation of serum PLGF levels and presence of GDM. We found that growth of
      beta cell mass during pregnancy was significantly impaired by l-NAME injection,
      as a result of reduced beta cell proliferation. This may explain the higher risk
      of developing GDM in patients with PE. Moreover, provision of exogenous PLGF in l
      NAME-treated pregnant mice significantly rescued beta cell proliferation, with
      subsequent increase in beta cell mass, suggesting that shortage in PLGF may be
      responsible for impaired beta cell growth and higher occurrence of GDM in
      patients with PE. CONCLUSIONS: Our study highlighted a pivotal role for PLGF in
      prevention and treatment of GDM in patients with PE.

PMID- 25594240
TI  - Local energy gap opening induced by hemin dimerization in aqueous solution.
AB  - The local electronic structure of the hemin Fe center has been investigated by X
      ray absorption and emission spectroscopy (XAS/XES) for hemin in aqueous solution
      where hemin dimerization occurs. The XAS and XES spectra of the hemin dimer were
      then compared with those of the hemin monomer we previously studied in dimethyl
      sulfoxide solution. A local energy gap opening at the Fe sites was observed for
      the hemin dimer, with the occupied valence states shifted to lower binding
      energies, while the unoccupied valence states share the same energies as the
      hemin monomer. Such a gap opening is argued to originate from the Fe 3d orbital
      localization induced by hemin dimerization in aqueous solution. 

PMID- 25594239
TI  - Could first-trimester assessment of placental functions predict preeclampsia and
      intrauterine growth restriction? A prospective cohort study.
AB  - OBJECTIVE: To examine the role of first-trimester uterine artery Doppler, serum
      beta-hCG and pregnancy-associated placental protein-A (PAPP-A) in prediction of
      preeclampsia and IUGR. METHODS: A total of 100 pregnant women in the 11-14 weeks'
      gestation were examined using uterine artery Doppler, serum beta-hCG and PAPP-A.
      All women were followed-up for development of preeclampsia or IUGR. RESULTS: A
      total of 94 women completed the study of which 7 (7.4%) developed complications.
      Uterine artery PI and RI were significantly higher whereas serum beta-hCG and
      PAPP-A levels were significantly reduced in patients who developed complications
      when compared with those who did not. Uterine artery PI had the highest
      sensitivity (100%) but a low specificity (56% and 45%) in prediction of
      preeclampsia and IUGR, respectively. Adding PAPP-A to uterine artery PI elevated
      the specificity into 94.44% and 95.51%, respectively. Combined PI and beta-hCG
      elevated the specificity into 88.89% and 89.89%, respectively. CONCLUSION: Our
      study suggests that first-trimester uterine artery impedance, as measured by
      Doppler ultrasound as well as low serum biomarkers (beta-hCG and PAPP-A) can be
      used for prediction of preeclampsia and IUGR. The most sensitive is uterine
      artery PI. Adding beta-hCG to PI improves specificity in prediction of both
      preeclampsia and IUGR. Uterine artery PI plus PAPP-A is the best combination for
      prediction of both preeclampsia and IUGR.

PMID- 25594241
TI  - Assessment of shoulder external rotation range-of-motion on throwing athletes:
      the effects of testing end-range determination (active versus passive).
AB  - The purpose of this study was to compare the effects of active or passive end
      range determination (supine position) for external rotation range of motion (ROM)
      in overhead throwing athletes and verify if athletes' ROM is similar to non
      athletes. Kinematic data from the dominant shoulder of 24 healthy male subjects,
      divided into two groups (12 athletes and 12 non-athletes) were recorded at end
      range external rotation, thoracohumeral and glenohumeral external rotation angles
      were compared and a 2-way repeated-measures ANOVA was used to calculate the
      effects of end-range determination (passive versus active) across groups (athlete
      and non-athlete). A significant main effect (p < 0.001) on both thoracohumeral
      and glenohumeral external end-range angles was observed while the highest end
      range determination values were associated with passive motion. No differences
      were observed between the athletic or non-athletic groups for either
      thoracohumeral (p = 0.784) or glenohumeral (p = 0.364) motion. 

PMID- 25594242
TI  - DNA topoisomerase-directed anticancerous alkaloids: ADMET-based screening,
      molecular docking, and dynamics simulation.
AB  - Topoisomerases (Topo I and II) have been looked as crucial targets against
      various types of cancers. In the present paper, 100 anticancerous alkaloids were
      subjected to in silico absorption, distribution, metabolism, excretion, and
      toxicity (ADMET) analyses to investigate their pharmacokinetic properties. Out of
      100 alkaloids, only 18 were found to fulfill all the ADMET descriptors and obeyed
      the Lipinski's rule of five. All the 18 alkaloids were found to dock successfully
      within the active site of both Topo I and II. A comparison of the inhibitory
      potential of 18 screened alkaloids with those of selected drugs revealed that
      four alkaloids (oliveroline, coptisine, aristolactam, and piperine) inhibited
      Topo I, whereas six alkaloids (oliveroline, aristolactam, anonaine, piperine,
      coptisine, and liriodenine) inhibited Topo II more strongly than those of their
      corresponding drugs, topotecan and etoposide, respectively, with oliveroline
      being the outstanding. The stability of the complexes of Topo I and II with the
      best docked alkaloid, oliveroline, was further analyzed using 10 nSec molecular
      dynamics simulation and compared with those of the respective drugs, namely,
      topotecan and etoposide, which revealed stabilization of these complexes within 5
      nSec of simulation with better stability of Topo II complex than that of Topo I. 

PMID- 25594243
TI  - Comments on 'Saddleback deformities in yellowfin bream, Acanthopagrus australis
      (Gunther), from South-East Queensland' by Diggles (2013).

PMID- 25594244
TI  - A qualitative study exploring counselling for release of information to
      participants of a donor-assisted conception programme.
AB  - Worldwide, donor-assisted conceptions are increasing with legislative reforms in
      some countries providing opportunities for participants of a donor-assisted
      conception programme, i.e. recipients, donors, donor-conceived adults and their
      genetically related siblings and half-siblings, to access information. Whilst
      policy and practice for accessing donor-identifying information vary, there has
      been no research exploring the perceptions and experiences of those who provide
      the service. This study aimed to explore the perceptions and experiences of
      Australian and New Zealand infertility counsellors who provide counselling for
      release of information to participants of a donor-assisted conception programme.
      Using a qualitative research design, in-depth interview data of six infertility
      counsellors were thematically analysed to identify key themes. We report the
      primary themes that emerged from the data which include professional perspectives
      on the role of counsellor in the counselling process, the professional and
      societal responsibility to provide counselling, and influences on professional
      practice. Findings from this qualitative study can be used as a platform for
      larger international studies on the clinical practice of donor information
      release and to inform clinical practice and service delivery. The implications of
      these results for policy and future longitudinal research are also discussed. 

PMID- 25594245
TI  - Association between Cardiovascular Drugs and Chronic Kidney Disease in Non
      Institutionalized Elderly Patients.
AB  - Concern about the renal safety of commonly used cardiovascular drugs with
      demonstrated clinical benefit appears to be an obstacle to their use in the
      elderly. The objective was to describe the relationship between cardiovascular
      drugs and chronic kidney disease (CKD) in elderly individuals in the real-life
      setting. This is an ancillary study of the prospective non-interventional S.AGE
      (aged individuals) cohort. General physicians were free to prescribe any drug
      their patients needed. The participants were non-institutionalized patients aged
      65 years and older treated by their primary physician for either chronic pain or
      atrial fibrillation or type 2 diabetes mellitus. The estimated glomerular
      filtration rate (eGFR) derived from the CKD-EPI formula was determined at
      inclusion and every year during 2 years of follow-up. This study comprised 2505
      patients aged 77.8 +/- 6.2 years. At inclusion, the factors associated with CKD
      (eGFR < 60 ml/min/1.73 m(2) ) in multivariate analysis were age, female gender,
      hypertension, heart failure, history of atherothrombotic disease and renin
      angiotensin system blockers, loop diuretics and calcium channel inhibitors.
      Introduction of each of these three drug classes during the follow-up period led
      to only a small decrease in the eGFR: -3.8 +/- 12.7 (p < 0.0006), -2.2 +/- 12.0
      (p < 0.003) and -1.0 +/- 13.4 ml/min./1.73 m(2) (NS), respectively. Only the
      introduction of loop diuretics was associated with CKD (OR 1.91, 95% CI: 1.25
      2.90; p = 0.002). Renal safety of cardiovascular drugs in the elderly appears
      acceptable and should not be a barrier to their use. 

PMID- 25594246
TI  - Wheelchair-specific fitness of inactive people with long-term spinal cord injury.
AB  - OBJECTIVES: To describe wheelchair-specific anaerobic work capacity, isometric
      strength and peak aerobic work capacity of physically inactive people with long
      term spinal cord injury using outcomes of tests that are feasible for use in
      rehabilitation centres, and to determine associations among these fitness
      components. DESIGN: Cross-sectional study. PARTICIPANTS: Manual wheelchair users
      with spinal cord injury for at least 10 years, who were inactive based on a norm
      score of a physical activity questionnaire (n = 29; 22 men; 20 with paraplegia;
      median age 53 years). METHODS: Participants performed 3 exercise tests in their
      own wheelchair to determine: highest 5-s power output over 15-m overground
      sprinting (P5-15m); highest 3-s isometric push-force (Fiso); and peak power
      output (POpeak) and peak oxygen uptake (VO2peak) over a peak test. RESULTS:
      Median (interquartile range) was in P5-15m 16.1 W (9.4-20.9); in Fiso 399 N (284
      610); in POpeak 40.9 W (19.1-54.9); and in VO2peak 1.26 l/min (0.80-1.67).
      Correlations among outcomes of fitness components were weak (r = 0.50-0.67, p <
      0.01), except for P5-15m with POpeak (r = 0.79, p < 0.001). CONCLUSION: All
      fitness components measured in this sample were at relatively low levels,
      implying a specific need for interventions to improve wheelchair-specific
      fitness. The weak-to-moderate associations among components imply that separate
      tests should be used when monitoring wheelchair-specific fitness in
      rehabilitation centres.

PMID- 25594247
TI  - Prevalence of fetal alcohol syndrome in a population-based sample of children
      living in remote Australia: the Lililwan Project.
AB  - AIM: Aboriginal leaders concerned about high rates of alcohol use in pregnancy
      invited researchers to determine the prevalence of fetal alcohol syndrome (FAS)
      and partial fetal alcohol syndrome (pFAS) in their communities. METHODS:
      Population-based prevalence study using active case ascertainment in children
      born in 2002/2003 and living in the Fitzroy Valley, in Western Australia (April
      2010-November 2011) (n = 134). Socio-demographic and antenatal data, including
      alcohol use in pregnancy, were collected by interview with 127/134 (95%)
      consenting parents/care givers. Maternal/child medical records were reviewed.
      Interdisciplinary assessments were conducted for 108/134 (81%) children. FAS/pFAS
      prevalence was determined using modified Canadian diagnostic guidelines. RESULTS:
      In 127 pregnancies, alcohol was used in 55%. FAS or pFAS was diagnosed in 13/108
      children, a prevalence of 120 per 1000 (95% confidence interval 70-196). Prenatal
      alcohol exposure was confirmed for all children with FAS/pFAS, 80% in the first
      trimester and 50% throughout pregnancy. Ten of 13 mothers had Alcohol Use
      Disorders Identification Test scores and all drank at a high-risk level. Of
      children with FAS/pFAS, 69% had microcephaly, 85% had weight deficiency and all
      had facial dysmorphology and central nervous system abnormality/impairment in
      three to eight domains. CONCLUSIONS: The population prevalence of FAS/pFAS in
      remote Aboriginal communities of the Fitzroy Valley is the highest reported in
      Australia and similar to that reported in high-risk populations internationally.
      Results are likely to be generalisable to other age groups in the Fitzroy Valley
      and other remote Australian communities with high-risk alcohol use during
      pregnancy. Prevention of FAS/pFAS is an urgent public health challenge.

PMID- 25594248
TI  - Sustained reprogramming of the estrogen response after chronic exposure to
      endocrine disruptors.
AB  - The pervasive nature of estrogenic industrial and dietary compounds is a growing
      health concern linked to cancer, obesity, and neurological disorders. Prior
      analyses of endocrine disruptor action have focused primarily on the short-term
      consequences of exposure. However, these studies are unlikely to reflect the
      consequences of constant exposures common to industrialized countries. Here we
      examined the global effects of long-term endocrine disruption on gene
      transcription and estrogen signaling. Estrogen-dependent breast cancer cell lines
      were chronically treated with physiologically relevant levels of bisphenol A or
      genistein for more than 70 passages. Microarray analysis demonstrated global
      reprogramming of the transcriptome when compared with a similarly cultured
      control cell line. Estrogen-responsive targets showed diminished expression in
      both the presence and absence of estrogen. Estrogen receptor recruitment, H3K4
      monomethylation, and deoxyribonuclease accessibility were reduced at nearby
      response elements. Based on these observations, we investigated the potential of
      long-term endocrine disruptor exposure to initiate persistent transcriptional
      reprogramming. Culture of chronically exposed cell lines in the absence of the
      endocrine disruptors did not reverse many of the signaling defects that
      accumulated during treatment. Taken together, these data demonstrate that chronic
      exposure to endocrine disrupting compounds can permanently alter physiological
      hormone signaling. 

PMID- 25594249
TI  - Mitochondrial malic enzyme 3 is important for insulin secretion in pancreatic
      beta-cells.
AB  - Pancreatic beta-cells with severely knocked down cytosolic malic enzyme (ME1) and
      mitochondrial NAD(P) malic enzyme (ME2) show normal insulin secretion. The
      mitochondrial NADP malic enzyme (ME3) is very low in pancreatic beta-cells, and
      ME3 was previously thought unimportant for insulin secretion. Using short hairpin
      RNAs that targeted one or more malic enzyme mRNAs in the same cell, we generated
      more than 25 stable INS-1 832/13-derived insulin cell lines expressing extremely
      low levels of ME1, ME2, and ME3 alone or low levels of two of these enzymes in
      the same cell line. We also used double targeting of the same Me gene to achieve
      even more severe reduction in Me1 and Me2 mRNAs and enzyme activities than we
      reported previously. Knockdown of ME3, but not ME1 or ME2 alone or together,
      inhibited insulin release stimulated by glucose, pyruvate or 2-aminobicyclo
      [2,2,1]heptane-2-carboxylic acid-plus-glutamine. The data suggest that ME3, far
      more than ME1 or ME2, is necessary for insulin release. Because ME3 enzyme
      activity is low in beta-cells, its role in insulin secretion may involve a
      function other than its ME catalytic activity. 

PMID- 25594251
TI  - Biphasic vs basal bolus insulin regimen in Type 2 diabetes: a systematic review
      and meta-analysis of randomized controlled trials.
AB  - AIM: We aim to evaluate the effects of biphasic insulin compared with a basal
      bolus insulin regimen on glycaemic control, total daily insulin requirements,
      risk of hypoglycaemia, weight and quality of life in patients with diabetes
      mellitus. METHODS: MEDLINE, EMBASE, PubMed and Scopus databases were searched for
      studies up to November 2013. Interventions that lasted for more than four weeks
      and were reported in English were considered for the review. Meta-analysis was
      performed on eligible studies. RESULTS: Fifteen randomized controlled trial
      studies, involving 4384 patients, were included. Greater HbA1c reductions were
      seen with basal-bolus compared with biphasic insulin regimens, between-treatment
      weighted mean difference (WMD) for baseline-to-endpoint changes in HbA1c was 
      0.2% (95% CI: -0.36 to -0.03) [-2.2 (-3.9, -0.3) mmol/mol]. In non-insulin naive
      (n = 8) patients with Type 2 diabetes, HbA1c reduction was greater in the basal
      bolus group; WMD = -0.22% (95% CI: -0.42 to -0.02) [-2.4 (-4.6, -0.2) mmol/mol],
      but in insulin naive patients (n = 5), HbA1c was equivalent between the two
      regimens; WMD (-0.15% (95% CI: -0.52 to 0.22) [-1.6 (-5.7, 2.4) mmol/mol]. Total
      daily insulin requirements and weight were increased with both regimens, whereas
      hypoglycaemia rates were comparable between the two regimens. Greater HbA1c
      reduction was observed in the basal bolus group compared with the biphasic
      regimen at the expense of higher daily insulin requirements and weight gain, but
      with no greater risk of hypoglycaemia. CONCLUSIONS: Biphasic and basal bolus
      regimens were equally effective in reducing HbA1c in insulin naive patients with
      Type 2 diabetes and both regimens are equally effective for initiating insulin in
      Type 2 diabetes.

PMID- 25594252
TI  - Toxic effects of systemic cisplatin on rat eyes and the protective effect of
      hesperidin against this toxicity.
AB  - CONTEXT: In the present study, cisplatin (CP) induced eye toxicity and the
      beneficial effect of hesperidin (HP) was investigated. METHODS: Twenty-eight rats
      were equally divided into four groups; the first group was kept as control. In
      the second and third group, CP and HP were given at the doses of 7 mg/kg and 50
      mg/kg/d, respectively. In the fourth group, CP and HP were given together at the
      same doses. Tissue samples were collected on day 14 of CP treatment. RESULTS: The
      results demonstrated that CP caused a significant increase in thiobarbituric acid
      reactive substances (TBARS) levels and decrease of glutathione levels and
      antioxidant enzyme activity (catalase, superoxide dismutase and glutathione
      peroxidase) in eye tissues compared to other groups, HP prevented these effects
      of CP. Besides, CP led to histopathological damage in the retina and cornea. On
      the other hand, HP treatment prevented histopathological effects of CP.
      CONCLUSION: CP had severe dose-limiting toxic effects and HP treatment can be
      beneficial against the toxic ocular effects of CP. Thus, it appears that co
      administration of HP with CP may be a useful approach to attenuate the negative
      effects of CP on the eye.

PMID- 25594250
TI  - The role of colonic bacteria in the metabolism of the natural isoflavone daidzin
      to equol.
AB  - Isoflavones are found in leguminous plants, especially soybeans. They have a
      structural similarity to natural estrogens, which enables them to bind to
      estrogen receptors and elicit biological activities similar to natural estrogens.
      They have been suggested to be beneficial for the prevention and therapy of
      hormone-dependent diseases. After soy products are consumed, the bacteria of the
      intestinal microflora metabolize isoflavones to metabolites with altered
      absorption, bioavailability, and estrogenic characteristics. Variations in the
      effect of soy products have been correlated with the isoflavone metabolites found
      in plasma and urine samples of the individuals consuming soy products. The
      beneficial effects of the soy isoflavone daidzin, the glycoside of daidzein, have
      been reported in individuals producing equol, a reduction product of daidzein
      produced by specific colonic bacteria in individuals called equol producers.
      These individuals comprise 30% and 60% of populations consuming Western and soy
      rich Asian diets, respectively. Since the higher percentage of equol producers in
      populations consuming soy-rich diets is correlated with a lower incidence of
      hormone-dependent diseases, considerable efforts have been made to detect the
      specific colonic bacteria involved in the metabolism of daidzein to the more
      estrogenic compound, equol, which should facilitate the investigation of the
      metabolic activities related to this compound. 

PMID- 25594253
TI  - Mercury content in marketed cosmetics: analytical survey in Shijiazhuang, China.
AB  - CONTEXT: Mercury is one of the skin-lightening ingredients in cosmetics as
      mercury ions are thought to inhibit the synthesis of the skin pigment melanin in
      melanocyte cells. OBJECTIVE: The objective of this study was to evaluate the
      mercury levels of cosmetics currently marketed in Shijiazhuang, a northern city
      in China. METHODS: We collected 146 random cosmetic samples and analyzed for
      mercury concentrations or levels by cold vapor atomic absorption spectrometry.
      RESULTS: Among the 146 samples, 134 (91.8%) were positive for mercury, and the
      concentrations of mercury ranged from not detectable to 592 ng/g. Cosmetic
      samples for children and babies had the highest detection rate (100%), followed
      by shampoo and hair conditioner (92.3%) and skin-lightening cream (92.0%). All of
      them were lower than the acceptable limit (1 MUg/g) in China. DISCUSSION AND
      CONCLUSIONS: Cosmetics for skin had the highest mean mercury content (45 ng/g),
      followed by hair products (42.1 ng/g). The concentrations of mercury detected in
      samples were lower than the current legal limit in China, indicating it may not
      pose a risk to consumers.

PMID- 25594254
TI  - The Effect of Cyclic Loading on the Compressive Strength of Core Build-Up
      Materials.
AB  - PURPOSE: To evaluate the effect of cyclic loading on compressive strength of core
      build-up materials. MATERIALS AND METHODS: Four dual-cured composites (Core.X
      Flow, Grandio Core, Bright Flow Core, Spee-Dee) and one light-cured reinforced
      resin-modified glass ionomer (Fuji II LC) were tested. One hundred cylindrical
      specimens (4 mm * 6 mm) were prepared. Each material had two groups (ten
      specimens to be tested under static loading and ten specimens to be tested after
      cyclic loading). The specimens were stored wet, and after 30 days, one group of
      each material was cyclically loaded (for 250,000 cycles with a frequency of 1.6
      Hz under stress load of 68.6 N) in a chewing simulator CS-4.2. Then specimens
      were subjected to static compressive loading until failure in a universal testing
      machine. RESULTS: Mean compressive strength values before cycling ranged from 144
      MPa (15.8) for Fuji II LC to 277 MPa (23.2) for Grandio Core. Independent t-test
      showed no statistically significant difference (p > 0.05) in the compressive
      strength of each material before and after cycling (p = 0.7 Grandio Core, p = 0.3
      Core. X Flow, p = 0.6 Bright Flow Core, p = 0.2 Spee-Dee, p = 0.6 Fuji II LC);
      however, there was a statistically significant difference between the materials
      when comparing before and after cycling. CONCLUSIONS: All tested materials showed
      no reduction in the compressive strength after cycling. Therefore, the tested
      materials can survive 1 year in service without a reduction in compressive
      strength.

PMID- 25594256
TI  - Venous thrombosis in pancreaticobiliary tract cancer: outcome and prognostic
      factors.
AB  - BACKGROUND: The differences in outcome among cancer patients with incidental vs.
      symptomatic venous thromboembolism (VTE) are unknown. In this study, patients
      with extrahepatic pancreaticobiliary tract cancer (PBC) were selected for a
      prospective cohort study between February 2008 and February 2011. METHODS: At the
      time of cancer diagnosis, all patients were examined for deep vein thrombosis
      with bilateral compression ultrasonography (biCUS). Computed tomography pulmonary
      angiography was also performed to diagnose pulmonary embolisms. After inclusion,
      the patients were followed up with clinical examinations, blood collections, and
      biCUS. RESULTS: A total of 121 PBC patients were enrolled. At the time of cancer
      diagnosis, 15 patients had experienced a VTE (12.4%, 95% confidence interval [CI]
      7.1-19.6), including six symptomatic and nine incidental cases. A total of 25
      first-time VTE events were identified (20.7%; 95% CI 13.8-29.0). Patients with a
      VTE had reduced survival, with a median overall survival (OS) of 4.4 months (95%
      CI 2.2-11.5). The median OS of the patients with incidental VTE was 3.0 months
      (95% CI 0.1-15.0), which was not different from the median OS of the patients
      with symptomatic VTE (5.0 months; 95% CI 2.1-14.5). The median OS was 11.9 months
      (95% CI 8.1-14.7) in the PBC patients with no VTEs. CONCLUSION: The occurrence of
      a VTE event in a PBC patient within the first months of the disease is associated
      with significantly increased mortality.

PMID- 25594257
TI  - Eduardo Bustos-Obregon (1937-2014).

PMID- 25594255
TI  - Allergen sensitization profiles in a population-based cohort of children
      hospitalized for asthma.
AB  - RATIONALE: Allergen sensitization is associated with asthma morbidity. A better
      understanding of allergen sensitization patterns among children hospitalized for
      asthma could help clinicians tailor care more effectively. To our knowledge,
      however, sensitization profiles among children hospitalized for asthma are
      unknown. OBJECTIVES: We sought to describe allergen sensitization profiles and
      the distribution of self-reported in-home exposures among children hospitalized
      for asthma. We also sought to assess how sensitization profiles varied by
      sociodemographic and clinical factors. METHODS: This population-based cohort
      study includes data for 478 children, aged 4-16 years, hospitalized for an asthma
      exacerbation. Predictors included child age, race, sex, insurance status,
      reported income, salivary cotinine, exposure to traffic-related air pollution,
      asthma and atopic history, and season of admission. Outcomes included serum IgE
      specific to Alternaria alternata/A. tenuis, Aspergillus fumigatus, American
      cockroach, mouse epithelium, dust mite (Dermatophagoides pteronyssinus and
      farinae), cat dander, and dog dander (deemed sensitive if IgE >= 0.35). Self
      reported adverse exposures included mold/mildew, water leaks, cockroaches,
      rodents, and cracks or holes in the walls or ceiling. Presence of carpeting and
      furry pets was also assessed. MEASUREMENTS AND MAIN RESULTS: More than 50% of
      included patients were sensitized to each of Alternaria, Aspergillus, dust mite,
      cat dander, and dog dander; 28% were sensitized to cockroach and 18% to mouse.
      Roughly 68% were sensitized to three or more allergens with evidence of
      clustering. African American children, compared with white children, were more
      likely to be sensitized to Alternaria, Aspergillus, cockroach, and dust mite (all
      P<0.01). White children were more likely to be sensitized to mouse, cat, and dog
      (all P<0.01). Lower income was associated with cockroach sensitization whereas
      higher income was associated with dog and cat sensitization (all P<0.01). Atopic
      history was associated with sensitization to three or more allergens (P<0.01).
      Although 42% reported exposure to at least one adverse in-home exposure (and 72%
      to carpet, 51% to furry pets), only weak relationships were seen between reported
      exposures and sensitizations. CONCLUSIONS: Most children admitted to the hospital
      for asthma exacerbations are sensitized to multiple indoor allergens. Atopy on
      the inpatient unit serves as a potential target for improvement in chronic asthma
      management.

PMID- 25594258
TI  - Answer to the letter to the editor concerning 'effects of quercetin and fish n-3
      fatty acids on testicular injury induced by ethanol in rats'.

PMID- 25594259
TI  - Risk factors for hepatitis B virus recurrence after living donor liver
      transplantation: A 17-year experience at a single center.
AB  - AIM: The incidence of hepatitis B virus (HBV) recurrence after liver
      transplantation (LT) has been reduced by prophylaxis with hepatitis B
      immunoglobulin (HBIG) and nucleoside analogs, but the factors associated with HBV
      recurrence are unclear. The aim of this study was to determine the risk factors
      associated with HBV recurrence after living donor LT (LDLT). METHODS: A
      retrospective review was performed for 45 patients (28 male and 17 female; median
      age, 54 years) who underwent LDLT for HBV-related liver disease and were followed
      up for at least 6 months between October 1996 and June 2013. The virological
      data, tumor burden, antiviral therapy and immunosuppressive therapy were
      evaluated and compared between the HBV recurrence ad non-recurrence groups.
      RESULTS: Seven of the 45 patients (15.6%) developed post-LT HBV recurrence. The
      median interval between LDLT and HBV recurrence was 23.7 months (range, 0.8
      35.9). Three of the seven patients (42.9%) developed recurrence after cessation
      of HBIG, and three (42.9%) were cases with hepatocellular carcinoma (HCC)
      recurrence after LDLT. The remaining case underwent transplantation from a donor
      with positive hepatitis B surface antigen. Based on the univariate and
      multivariate analyses, HBIG cessation (hazard ratio [HR], 20.17; 95% confidence
      interval [95% CI], 2.091-194.593; P = 0.009) and HCC recurrence (HR, 30.835; 95%
      CI, 3.132-303.593; P = 0.003) were independent risk factors for HBV recurrence
      after LDLT. CONCLUSION: In LDLT patients, cessation of HBIG and HCC recurrence
      were risk factors associated with HBV recurrence, so careful monitoring for
      serological HBV markers is needed in patients with these factors.

PMID- 25594260
TI  - P2X7/PANX1 as a new target for melanoma?

PMID- 25594261
TI  - L2-Proficiency-Dependent Laterality Shift in Structural Connectivity of Brain
      Language Pathways.
AB  - Diffusion tensor imaging (DTI) and a longitudinal language learning approach were
      applied to investigate the relationship between the achieved second language (L2)
      proficiency during L2 learning and the reorganization of structural connectivity
      between core language areas. Language proficiency tests and DTI scans were
      obtained from German students before and after they completed an intensive 6-week
      course of the Dutch language. In the initial learning stage, with increasing L2
      proficiency, the hemispheric dominance of the Brodmann area (BA) 6-temporal
      pathway (mainly along the arcuate fasciculus) shifted from the left to the right
      hemisphere. With further increased proficiency, however, lateralization dominance
      was again found in the left BA6-temporal pathway. This result is consistent with
      reports in the literature that imply a stronger involvement of the right
      hemisphere in L2 processing especially for less proficient L2 speakers. This is
      the first time that an L2 proficiency-dependent laterality shift in the
      structural connectivity of language pathways during L2 acquisition has been
      observed to shift from left to right and back to left hemisphere dominance with
      increasing L2 proficiency. The authors additionally find that changes in
      fractional anisotropy values after the course are related to the time elapsed
      between the two scans. The results suggest that structural connectivity in (at
      least part of) the perisylvian language network may be subject to fast dynamic
      changes following language learning. 

PMID- 25594262
TI  - Interactions between structural and chemical biomimetism in synthetic stem cell
      niches.
AB  - Advancements in understanding stem cell functions and differentiation are of key
      importance for the clinical success of stem-cell-based therapies. 3D structural
      niches fabricated by two-photon polymerization are a powerful platform for
      controlling stem cell growth and differentiation. In this paper, we investigate
      the possibility of further controlling stem cell fate by tuning the mechanical
      properties of such niches through coating with thin layers of biomimetic
      hyaluronan-based and gelatin-based hydrogels. We first assess the
      biocompatibility of chemical coatings and then study the interactions between
      structural and chemical biomimetism on the response of MSCs in terms of
      proliferation and differentiation. We observed a clear effect of the hydrogel
      coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated
      niches we observed a stronger metabolic activity and commitment toward the osteo
      chondral lineage with respect to hyaluronan-coated niches. Conversely, a
      reduction in the homing effect was observed in all the coated niches, especially
      in gelatin-coated niches. This study demonstrates the feasibility of controlling
      independently different mechanical cues, in bioengineered stem cell niches, i.e.
      the 3D scaffold geometry and the surface stiffness. This will allow, on the one
      hand, understanding their specific role in stem cell proliferation and
      differentiation and, on the other hand, finely tuning their synergistic effect. 

PMID- 25594263
TI  - Chromone derivatives from a sponge-derived strain of the fungus Corynespora
      cassiicola.
AB  - Twelve new chromone derivatives, corynechromones A-L (1-12), were isolated from
      the sponge-derived fungus Corynespora cassiicola XS-200900I7. Among them, 1/2,
      3/4, 5/6, and 7/8 were pairs of epimers. The planar structures were determined by
      extensive NMR spectroscopic data. The absolute configurations of 1-10 were
      assigned by the modified Mosher's method and TDDFT ECD calculations together with
      comparison of their CD spectra. These are the first chromone derivatives reported
      from the genus Corynespora. A possible rule to determine the absolute
      configurations at C-2 in chromone derivatives by CD was proposed. 

PMID- 25594265
TI  - [Eating disorder research over the next ten years - quo vadis?].

PMID- 25594266
TI  - [The development of the German health system in regard to treatment of eating
      disorders].
AB  - The ongoing change in the German health care system challenges all those dealing
      scientifically with the treatment of eating disorders. The process of change
      provides an opportunity to rethink the entire range from outpatient treatment to
      intensive residential treatment of mental disorders. Improving trans-sectoral
      medical care for eating disorders could thereby play a leading role. The problem
      of unsatisfactory long-term courses in view of the high mortality in anorexia
      nervosa, cannot be met only by successful weight restitution but by an adaptive
      approach for long term maintainment of a healthy body weight. 

PMID- 25594264
TI  - Innovative Research Design Exploring the Effects of Physical Activity and
      Genetics on Cognitive Performance in Community-Based Older Adults.
AB  - Physical activity is predictive of better cognitive performance and lower risk of
      Alzheimer's disease (AD). The apolipoprotein E gene (APOE) is a susceptibility
      gene for AD with the e4 allele being associated with a greater risk of AD. Cross
      sectional and prospective research shows that physical activity is predictive of
      better cognitive performance for those at greater genetic risk for AD. However,
      the moderating role of APOE on the effects of a physical activity intervention on
      cognitive performance has not been examined. The purpose of this manuscript is to
      justify the need for such research and to describe the design, methods, and
      recruitment tactics used in the conductance of a study designed to provide
      insight as to the extent to which cognitive benefits resulting from an 8-month
      physical activity program are differentiated by APOE e4 status. The effectiveness
      of the recruitment strategies and the feasibility of recruiting APOE e4 carriers
      are discussed. 

PMID- 25594267
TI  - [Perspectives of genetic research in eating disorders using the example of
      anorexia nervosa].
AB  - Genetic mechanisms are relevant for both body weight regulation and eating
      disorders (e.g. anorexia nervosa, AN). Although genome-wide association studies
      (GWAS) have so far identified about 100 chromosomal regions that influence body
      weight, only a small part of the variance could be explained by molecular genetic
      factors. For AN GWAS up to now did not reveal genome-wide significant loci. There
      are first hints for epigenetic mechanisms involved in the described phenotypes.
      Epigenomics can improve our understanding of the regulation of body weight
      including hunger (AN) and overnutrition (obesity). Since the prenatal phase is
      characterized by dramatic epigenetic changes, it can be regarded as vulnerable
      period for the epigenotype. Adult health and disease depend on prenatal and early
      postnatal development. Gene expression markers that are imprinted during this
      phase can be heritable at the cellular level. These markers can be altered by
      environmental factors. Altered epigenetic profiles had been described for obese
      individuals. In mice it was shown that an epigenetic modification of an obesity
      gene locus had been transferred to the next generation. The year to come will
      show whether the combined analysis of epigenomic and GWAS data will deepen our
      understanding of the underlying biological mechanisms.

PMID- 25594268
TI  - [What will the future of psychobiological research in eating disorders look
      like?].
AB  - The technical progress of brain imaging methods in recent years have decisively
      contributed to a better understanding of the neurobiological underpinnings of
      eating disorders. However, the identification and detection of underlying
      neurocircuits is complicated by the aetiological heterogeneity of clinically and
      psychopathologically defined eating disorder phenotypes. It is against this
      background that renowned scientists advocate that neurocircuit function should be
      the starting point for the upward investigation of behavioural responses and the
      downward research of constitutional genetic and molecular biological factors.
      According to this theory, psychobiological research of disturbed eating behaviour
      will follow to a greater extent a transdiagnostic and dimensional approach, and
      will be based on well characterized neurocircuits in the future. Furthermore, the
      latest findings in brain research will allow to investigate directly the
      interaction between neurocircuit function and energy metabolism in eating
      disorders. The typical onset of anorexia nervosa and bulimia nervosa in puberty
      suggest that age related biological and psychosocial alterations in this phase of
      life serve as a trigger for the beginning of the disease. Therefore, a greater
      integration of the developmental perspective as well as (epi-) genetic aspects in
      psychobiological research will be of great scientific interest in the future. 

PMID- 25594269
TI  - [Relevance of neuroimaging findings for diagnoses and treatment of adolescent
      anorexia nervosa].
AB  - Anorexia nervosa is associated with a marked loss of brain volumes during the
      acute stage of the disease. Due to the advances in neuroimaging methods during
      the last years our understanding of the consequences of starvation and the
      etiology of eating disorders has increased considerably, however, still the
      clinical relevance of these findings is limited. Thus, some future perspectives
      of neuroimaging findings for diagnoses and treatment of anorexia nervosa are
      summarized in the current review. 

PMID- 25594270
TI  - [New aspects in the treatment of adolescent anorexia nervosa].
AB  - Adolescent anorexia nervosa often takes a chronic and disabling course associated
      with reduced health-related quality of life in adulthood. The aim of this short
      review is to introduce new aspects on the somatic and psychotherapeutic treatment
      of AN, such as nutritional rehabilitation, prophylaxis of osteoporosis as well as
      new findings on the effect of treatment settings and new psychotherapeutic
      methods. 

PMID- 25594271
TI  - [Are there specific factors in the psychotherapy of anorexia nervosa?].
AB  - The present literature review examines the question of how general and specific
      factors can be differentiated in the psychotherapy of anorexia nervosa. Over the
      past 10 years different research trends have appeared. On the one hand
      subclassifications of new therapy approaches from several schools of therapy have
      been propagated (e.g. CBT-E, FPT), on the other hand generic treatment manuals
      have been published that are rather adapted to patients needs (e.g. SSCM, TTM).
      On a third way, currently therapy manuals for special subgroups have been
      developed, e.g. for chronic patients with anorexia nervosa or family-based
      manuals for adolescents. A completely different direction follows those
      approaches that are based on neuropsychological models and deficits in anorexia
      nervosa. Overall, the results of current studies have been promising, however,
      there has not been a winner yet, the race is still open!

PMID- 25594272
TI  - [How relevant are diagnostics and therapy in body image disorder?].
AB  - Body image-related interventions become increasingly important in the treatment
      of anorexia and bulimia nervosa. Previous studies concerning body image
      disturbance conducted by means of diverse research methods focused on different
      components of body image - the perceptive, cognitive-emotional and the behavioral
      component. However, regarding the etiology, maintenance and treatment of body
      image disturbance in eating disorders, many questions remain unanswered. An
      integrative perspective on the different body image components within a
      theoretical framework as well as the development of specific body image-related
      interventions according to individual indications would be desirable. 

PMID- 25594273
TI  - [Advances in the treatment of eating disorders].
AB  - The consideration of existing literature, especially in light of new knowledge of
      eating disorders and new diagnostic categories, highlights the necessity to
      increase the efficacy of current forms of therapy, and to develop novel therapies
      for eating disorders. This pertains, in particular, to bulimia nervosa and binge
      eating disorder. A considerable gain in knowledge is to be expected from a
      systematic analysis of the therapeutic process as well as the moderators and
      mediators. Furthermore, dissemination of evidence-based treatment methods in
      practical settings and an examination of stepped care models are important
      avenues of future research. 

PMID- 25594274
TI  - [Should we use new media in the treatment of eating disorders?].
AB  - The use of information and communication technologies ("e-mental health") has
      been suggested for the prevention and treatment of eating disorders as an
      addition to conventional treatment approaches. Guided internet-based self-help
      programs can be viewed as evidence-based treatment options for bulimia nervosa
      (BN) and binge eating disorder (BED) based on existing controlled studies. They
      represent an option within a stepped-care treatment approach and as relapse
      prevention after inpatient treatment. Additional fields of application for e
      mental health in eating disorders are prevention and early intervention as well
      as carers' support. 

PMID- 25594275
TI  - [Nutrition sciences in the treatment of eating disorders].
AB  - Several studies provide evidence for the existence of a hypermetabolic state of
      biological origin in recently weight recovered patients with anorexia nervosa. It
      remains unclear if current nutritional rehabilitation strategies are consistent
      with the resulting high energy requirements. Further insight into specific
      pathophysiological characteristics of energetic efficiency in patients with
      anorexia nervosa will help us to provide evidence based nutritional guidance.
      Basic nutritional research in this field is urgently required. 

PMID- 25594276
TI  - [Why do obese individuals suffer more often from psychiatric disorders?].
AB  - Previous research has indicated a complex association between obesity and
      psychiatric disorders caused by biological, psychosocial and environmental
      factors and dependent from the severity of obesity. For example, empirical data
      confirmed a reciprocal link between depression and obesity. Obesity was found to
      increase the risk of depression and vice versa. There is further a growing body
      of research pointing towards the important role of impulsivity in obesity,
      particularly in obese individuals with a binge eating disorder. 

PMID- 25594277
TI  - [Eating addiction - a behavioral addiction?].
AB  - With the introduction of the category Substance-Related and Addictive Disorders
      in DSM-5 for the first time behavioral addictions have entered the medical
      classification system. Food Addiction can be diagnosed with a 25-item
      questionnaire based on DSM-IV criteria for substance dependence. Food Addiction
      centers between substance-based addiction and non-substance-based behavioral
      addiction. To date, there is no evidence for a food component displaying
      addictive properties similar to psychotropic substances, such as cocaine or
      heroin. There is a lack of valid and reliable psychiatric-diagnostic criteria
      that aim to characterize Eating-Addiction as a behavioral addiction. 

PMID- 25594278
TI  - [Do we have to leave obesity treatment to the surgeons?].
AB  - The comparison of the largest bariatric surgery study (Swedish Obese Subjects,
      SOS) with almost 4000 surgical and conservatively treated patients and its
      conservative counterpart, the LookAHEAD study (Action for Help in Diabetes) with
      more than 5000 obese patients (average BMI 36 kg/m(2)) with type 2 diabetes
      showed that although both studies resulted in improved cardiovascular risk
      factors (bodyweight, HbA1c, HDL/LDL, blood pressure, sleep apnoe syndrome) only
      the SOS study and subsequent obesity surgery studies could verify their primary
      outcome hypothesis (significant reduction of the incidence of both cardiovascular
      deaths, non-fatal infarctions and strokes and hospitalization angina).
      Furthermore the SOS study could demonstrate a decreased mortality compared to the
      Look-AHEAD study. Despite a high psychological co-morbidity of obesity surgery
      patients the majority of studies also with follow-ups of more than 5 years
      demonstrates an improvement in mental functioning and quality of life. In
      contrast, there seems to be an increased risk for suicide about 3-4 years after
      the surgical intervention. Thus, while the majority of obesity surgery patients
      seems to benefit both physically and mentally, there is a minority that risks to
      take at least psychologically serious damage.

PMID- 25594279
TI  - Squaraine as a bright, stable and environment-sensitive far-red label for
      receptor-specific cellular imaging.
AB  - Herein, we show that a far-red arylidene-squaraine dye is stable against
      nucleophiles, in contrast to arene-squaraines. Owing to the fluorescence
      enhancement in apolar media together with high brightness and photostability,
      this dye was successfully applied to detect the oxytocin G protein-coupled
      receptor and monitor its internalization in living cells. 

PMID- 25594280
TI  - Reduced graphene oxide-supported CuPd alloy nanoparticles as efficient catalysts
      for the Sonogashira cross-coupling reactions.
AB  - Monodisperse CuPd alloy nanoparticles (NPs) were prepared by using a typical high
      temperature organic solution phase protocol comprising the coreduction of
      copper(II) acetylacetonate and palladium(II) acetylacetonate by morpholine-borane
      complex in oleylamine and 1-octadecene solution at 80  degrees C. The presented
      synthesis protocol allows us to control the composition of CuPd alloy NPs by
      simply tuning the initial ratio of metal precursors and the Cu-rich Cu75Pd25 NPs
      and Pd-rich Cu32Pd68 were synthesized besides the Cu48Pd52 NPs. Transmission
      electron microscopy studies revealed that most of the CuPd alloy NPs are
      polyhedral with an average diameter of 3.0+/-0.3 nm. The alloy structure of CuPd
      NPs was confirmed by the detailed X-ray diffraction and X-ray photoelectron
      spectroscopy analysis. As-prepared CuPd NPs were deposited on reduced graphene
      oxide (rGO) by using a liquid self-assembly method (rGO-CuPd) and used as
      catalysts in the Sonogashira cross-couplings of various aryl iodides or bromides
      and phenyl acetylene under the optimized reaction conditions. Among the three
      compositions of CuPd alloy NPs tested in the Sonogashira couplings, the rGO
      Cu48Pd52 gave the best yields in shorter reaction times and therefore it was used
      for further coupling reactions. The results demonstrated that rGO-Cu48Pd52 were
      efficient catalysts for the Sonogashira reaction of various aryl halides with
      phenylacetylene. The coupling reactions proceeded smoothly with both electron
      rich and electron-deficient aryl iodides and aryl bromides, affording the desired
      biaryl products in high yields. This is the first example of the employment of
      monodisperse CuPd alloy NPs with composition control in the Sonogashira cross
      coupling reactions.

PMID- 25594281
TI  - Structural covariance networks of striatum subdivision in patients with
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder associated with the
      striatum. Previous studies indicated that subdivisions of the striatum with
      distinct functional connectivity profiles contribute to different pathogeneses in
      PD. Segregated structural covariance (SC) pattern between the striatum and
      neocortex observed in healthy subjects, however, remain unknown in PD. The
      purpose of this study is to map and compare the subregional striatal SC network
      organization between 30 healthy controls and 48 PD patients and to investigate
      their association with the disease severity. The striatal SC network was
      statistically inferred by correlating the mean gray matter (GM) volume of six
      striatal subdivisions (including the bilateral dorsal caudate, superior ventral
      striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral
      putamen, and ventral rostral putamen) with the entire neocortical GM volume in
      voxel-wise manner. The PD patients revealed marked atrophy in the striatum,
      cerebellum, and extra-striatum neocortices. As predicted, segregated striatal SC
      network patterns were observed in both groups. This suggests that in PD,
      pathological processes occurring in the striatum affect the same striato-cortical
      networks that covary with the striatum in healthy brains. The PD patients further
      demonstrated atypical striatal SC patterns between the caudate, parahippocampus
      temporal cortices, and cerebellum, which corresponded to dopaminergic associated
      network. The areas with significant group differences in SC were further
      associated with disease severity. Our findings support previous studies
      indicating that PD is associated with altered striato-cortical networks, and
      suggest that structural changes in the striatum may result in a cascade of
      alterations in multiple neocortices.

PMID- 25594282
TI  - A shift in emission time profiles of fossil fuel combustion due to energy
      transitions impacts source receptor matrices for air quality.
AB  - Effective air pollution and short-lived climate forcer mitigation strategies can
      only be designed when the effect of emission reductions on pollutant
      concentrations and health and ecosystem impacts are quantified. Within integrated
      assessment modeling source-receptor relationships (SRRs) based on chemistry
      transport modeling are used to this end. Currently, these SRRs are made using
      invariant emission time profiles. The LOTOS-EUROS model equipped with a source
      attribution module was used to test this assumption for renewable energy
      scenarios. Renewable energy availability and thereby fossil fuel back up are
      strongly dependent on meteorological conditions. We have used the spatially and
      temporally explicit energy model REMix to derive time profiles for backup power
      generation. These time profiles were used in LOTOS-EUROS to investigate the
      effect of emission timing on air pollutant concentrations and SRRs. It is found
      that the effectiveness of emission reduction in the power sector is significantly
      lower when accounting for the shift in the way emissions are divided over the
      year and the correlation of emissions with synoptic situations. The source
      receptor relationships also changed significantly. This effect was found for both
      primary and secondary pollutants. Our results indicate that emission timing
      deserves explicit attention when assessing the impacts of system changes on air
      quality and climate forcing from short lived substances. 

PMID- 25594283
TI  - Determining the isomeric heterogeneity of neutral oligosaccharide-alditols of
      bovine submaxillary mucin using negative ion traveling wave ion mobility mass
      spectrometry.
AB  - Negative ions produced by electrospray ionization were used to evaluate the
      isomeric heterogeneity of neutral oligosaccharide-alditols isolated from bovine
      submaxillary mucin (BSM). The oligosaccharide-alditol mixture was preseparated on
      an off-line high-performance liquid chromatography (HPLC) column, and the
      structural homogeneity of individual LC fractions was investigated using a Synapt
      G2 traveling wave ion mobility spectrometer coupled between quadupole and time-of
      flight mass spectrometers. Mixtures of isomers separated by both chromatography
      and ion mobility spectrometry were studied. Tandem mass spectrometry (MS/MS) of
      multiple mobility peaks having the same mass-to-charge ratio (m/z) demonstrated
      the presence of different structural isomers and not differences in ion
      conformations due to charge site location. Although the oligosaccharide-alditol
      mixture was originally separated by HPLC, multiple ion mobility peaks due to
      structural isomers were observed for a number of oligosaccharide-alditols from
      single LC fractions. The collision-induced dissociation cells located in front of
      and after the ion mobility separation device enabled oligosaccharide precursor or
      product ions to be separated by ion mobility and independent fragmentation
      spectra to be acquired for isomeric carbohydrate precursor or product ions. MS/MS
      spectra so obtained for independent mobility peaks at a single m/z demonstrated
      the presence of structural variants or stereochemical isomers having the same
      molecular formula. This was observed both for oligosaccharide precursor and
      product ions. In addition, mobilities of both [M - H](-) and [M + Cl](-) ions,
      formed by adding NH4OH or NH4Cl to the electrospray solvent, were examined and
      compared for selected oligosaccharide-alditols. Better separation among
      structural isomers appeared to be achieved for some [M + Cl](-) anions. 

PMID- 25594285
TI  - Synthesis, biological evaluation, and structure-activity relationship study of
      novel stilbene derivatives as potential fungicidal agents.
AB  - A total of 22 novel stilbene derivatives containing the 1,3,4-oxadiazole moiety
      and trimethoxybenzene were designed and synthesized. Their chemical structures
      were characterized by (1)H and (13)C nuclear magnetic resonance, infrared, and
      high-resolution mass spectrometry. Bioassay results revealed that some of the
      title compounds showed potent in vivo fungicidal activities against three
      phytopathogenic fungi (Pseudoperonospora cubensis, Colletotrichum lagenarium, and
      Septoria cucurbitacearum) from cucurbits at 600 MUg/mL. Notably, compounds 4b,
      4d, 4i, 4k, and 4l exhibited a broad spectrum and remarkably high activities
      against those fungi, some of which even showed a comparable control efficacy to
      that of the commercial fungicides. Three-dimensional quantitative structure
      activity relationship based on comparative molecular field analysis with good
      predictive ability (q(2) = 0.516; r(2) = 0.920) was reasonably discussed. For the
      first time, the present work suggested that the stilbene derivatives containing
      the 1,3,4-oxadiazole moiety could be developed as potential fungicides for crop
      protection.

PMID- 25594286
TI  - Antimicrobial strategies based on natural products: recent progress in bio and
      nanotechnology.

PMID- 25594284
TI  - [II Guidelines on Cardiovascular Magnetic Resonance and Computed Tomography of
      the Brazilian Society of Cardiology and the Brazilian College of Radiology].

PMID- 25594287
TI  - Prevention of microbial communities: novel approaches based natural products.
AB  - Firmly attached to different living or non-living, solid or fluid surfaces rich
      in nutrients and moisture, microbial biofilm is a matter of great interest due to
      its major importance for the healthcare community. Depending on common strategies
      such as mutual protection and hibernation (quiescent bacteria), the resistance,
      survival and virulence of microbial communities have large implications for human
      pathology, clinical environment and biomedical devices. The microbial biofilm is
      continuously changing, stimulating inflammation, increasing vascular permeability
      and preventing the action of macrophages. About 80% of human infections affecting
      the gastrointestinal, genitourinary and respiratory systems, oral mucosa and
      teeth, eyes, middle ear and skin are caused by biofilm-associated microorganisms.
      Therefore, the search for modern strategies is even more important as microbial
      biofilms resistant to conventional antibiotics, antiseptics and disinfectants are
      involved in the frequent treatment failures of some chronic inflammatory diseases
      and wounds. Natural products containing secondary metabolites, such as aromatic
      compounds, sulphurated derivatives, terpenoids (essential oils) and alkaloids as
      quorum-sensing inhibitors and biofilm disruptors, are promising alternatives for
      the prophylaxis and treatment of chronic infections. Surface modification of
      medical devices with non-polar functionalized nanoparticles stabilizes the
      natural compounds antibiofilm activity and inhibits microbial adhesion and
      biofilm formation and growth for a longer period of time. In this regard, an
      interdisciplinary approach is needed due to the large number of natural
      derivatives alone or in combination with biocompatible and biodegradable micro-/
      nano-engineered materials. 

PMID- 25594288
TI  - Prosthetic devices with nanostructurated surfaces for increased resistance to
      microbial colonization.
AB  - This review highlights and discusses the impact of nanotechnology on the
      inhibition of microbial colonization and biofilm development on modified surface
      prosthetic devices. In the first part of the paper the current status of
      infections related to prosthetic devices and the inquiries resulting from the
      increased number of patients with these infections are briefly reviewed. Next we
      discuss several aspects about the implication of nanotechnology in prosthetic
      devices surface modification and its impact on the prevention of infections. The
      main aspects regarding the biocompatibility and the application of these
      nanomodified prosthetic devices in tissue engineering are also highlighted. 

PMID- 25594289
TI  - Antimicrobial Chitosan based formulations with impact on different biomedical
      applications.
AB  - Owing to its physico-chemical characteristics, the biodegradable and
      biocompatible polymer derived from crustacean shells, Chitosan is one of the
      preferred candidates for green biomedical applications and also for several
      industries. Its solubility in acid solutions and ability to form complexes with
      anionic macromolecules to yield nanoparticles, microparticles and hydrogels, as
      well as the ability of chitosan based nanocomposites to remain stable at
      physiological pH recommend this polymer for the development of efficient drug
      delivery systems. This paper reviews the main utilities of chitosan as a drug
      delivery component and describes the most recent technologies which utilize this
      polymer for developing nanostructured systems with antimicrobial effect, offering
      a perspective of using these findings in new, ecological biomedical applications.

PMID- 25594290
TI  - Essential oils with microbicidal and antibiofilm activity.
AB  - Plants are rich in a wide variety of secondary metabolites with antimicrobial
      properties. Phytochemistry studies on the plants extracts in general, and on
      essential oils (EOs) in particular are focused on the isolation and
      identification of the components of complex mixtures, in order to determine
      structure - activity correlations (i.e., physiological and/ or ecological roles,
      bases for the pharmacognosy studies). Problems as microbial resistance to
      existing antibiotics and the decline in the formulation of new antibiotics
      generated an increased interest in anti-infective herbal medicines. Some plants
      are known to be EOs producing, especialy superior plants, angiosperms and
      gymnosperms, belonging to approximately 50 families, most frequently Apiaceae,
      Lamiaceae, Myrtaceae, Pinaceae, Zingiberaceae, etc. The antimicrobial activity of
      EOs and of their components has been demonstrated on a variety of microorganisms.
      Our aim was to review relevant literature for identifying current research
      directions regarding EOs, in terms of antimicrobial effects, analysismethods and
      mechanisms of action. A plethora of methods have been used to test EOs
      antimicrobial properties concerning the microbial growth inhibition and/ or their
      anti-pathogenic effect. The reported methods contributed also to the elucidation
      of their mechanisms of action. Future research is needed for developing EOs
      related strategies in overlapping the multi-drug resistance and for reducing the
      required concentrations to achieve a particular antimicrobial and/ or antibiofilm
      effect to the human health benefit and/or for food safety purposes. 

PMID- 25594291
TI  - Antimicrobial and antiparasitic activity of lectins.
AB  - Antibiotic resistance is a major problem in current contemporary medicine and it
      has become a major concern of the 21st century. New resistance mechanisms
      developed by microorganisms spread greatly, threatening the ability to treat
      numerous infectious diseases, and increasing the number of nosocomial infections.
      Besides the role in immunology and glycobiology where they are used as
      hemaglutinine and identification of complex carbohydrates and glycoconjugates,
      lectins proved to mediate diversified biological functions like cytotoxicity,
      complement activation, cell-to-cell and host-pathogen communications, innate
      immune response, and cell-to-cell signalling. Recently, great interest has been
      developed for the research and applications of lectins in agriculture and
      medicine due to their antiparasitic and antimicrobial potentials. This review
      focuses on the recent data regarding the antimicrobial and antiparasitic
      activities of lectins, by presenting the role of lectins in host-pathogen
      interaction and also the cytotoxic effects on microorganisms and parasites.
      Identification and characterisation of new lectins with antimicrobial activity
      could serve as a natural alternative for the treatment of infections caused by
      antibiotic-resistant microorganisms and parasites. 

PMID- 25594292
TI  - Operative management of internal hemorrhoids.
AB  - An estimated 50% of the population over age 50 years have experienced
      hemorrhoidal symptoms at some point in their lives. Improved surgical techniques
      for internal hemorrhoids can reduce postoperative pain and facilitate a quicker
      recovery. 

PMID- 25594293
TI  - Hypovitaminosis D: A common deficiency with pervasive consequences.
AB  - Hypovitaminosis D is a common syndrome with well-established risk factors. Only
      recently, however, are the expansive implications of vitamin D deficiency
      becoming recognized, including cardiovascular complications, cancer, and
      dementia. The increased attention to the role of vitamin D has made its
      assessment more crucial in comprehensive patient management. 

PMID- 25594294
TI  - Primary immunodeficiency diseases: a primer for PCPs.
AB  - Primary care providers (PCPs) play a key role in identifying patients with
      primary immunodeficiency diseases (PIDDs). This diagnosis has implications for
      PCPs, as patients continue to require primary care and management after a PIDD
      diagnosis has been made. This review presents essential information for PCPs
      regarding PIDDs.

PMID- 25594295
TI  - Do not resuscitate.

PMID- 25594296
TI  - Diagnosis of primary versus secondary pediatric hypertension.

PMID- 25594298
TI  - NP advocacy: implications of the 2014 elections.

PMID- 25594300
TI  - Roundtable participants see a bright future for the convenient care industry.

PMID- 25594297
TI  - Engaging patients in their healthcare: cancer screening.

PMID- 25594303
TI  - Physical activity prescriptions in healthy populations: resources for Canadian
      nurse practitioners.
AB  - Canadian nurse practitioners' use of physical activity prescriptions is examined.
      Nurse practitioners use unstructured counseling techniques; have more
      opportunities with older adults; experience barriers; and want more education.
      Barriers are lack of time, lack of knowledge, and patient disinterest. Canadian
      resources are suggested to support physical activity prescriptions.

PMID- 25594305
TI  - Exploiting natural abundance 13C-15N coupling as a method for identification of
      nitrogen heterocycles: practical use of the HCNMBC sequence.
AB  - In this paper, we detail the results of (1)H-(15)N correlation data obtained via
      (13)C-(15)N coupling at natural abundance on a number of classes of azoles
      including pyrazoles, imidazoles and triazoles. The experiment produces data that
      is highly complementary to direct (1)H-(15)N HMBC type correlations in that it
      can provide (15)N chemical shift data for nitrogen that may not show up in the
      HMBC. This is particularly advantageous in the triazoles where (15)N chemical
      shift can be diagnostic of regiochemistry. Because of the consistency in JCN
      values among the azoles, the experiment produces distinctive correlation patterns
      that can be used for identification of regiochemistry. The experiment can also be
      used to directly measure (13)C-(15)N coupling constants.

PMID- 25594306
TI  - Synthesis of metronidazole-imprinted molecularly imprinted polymers by
      distillation precipitation polymerization and their use as a solid-phase
      adsorbent and chromatographic filler.
AB  - Metronidazole-imprinted polymers with superior recognition properties were
      prepared by a novel strategy called distillation-precipitation polymerization.
      The as-obtained polymers were characterized by Fourier-transform infrared
      spectroscopy, laser particle size determination and scanning electron microscopy,
      and their binding performances were evaluated in detail by static, kinetic and
      dynamic rebinding tests, and Scatchard analysis. The results showed that when the
      fraction of the monomers was 5 vol% in the whole reaction system, the prepared
      polymers afforded good morphology, monodispersity, and high adsorption capacity
      and excellent selectivity to the target molecule, metronidazole. The optimal
      binding performance is 12.41 mg/g for metronidazole just before leakage occurred
      and 38.51 mg/g at saturation in dynamic rebinding tests. Metronidazole-imprinted
      polymers were further applied as packing agents in solid-phase extraction and as
      chromatographic filler, both of which served for the detection of metronidazole
      in fish tissue. The results illustrated the recoveries of spiked samples ranged
      from 82.97 to 87.83% by using molecularly imprinted solid-phase extraction
      combined with a C18 commercial column and 93.7 to 101.2% by directly using the
      polymer-packed chromatographic column. The relative standard deviation of both
      methods was less than 6%. 

PMID- 25594307
TI  - Chiral phosphoric acid catalyzed highly enantioselective Friedel-Crafts
      alkylation reaction of C3-substituted indoles to beta,gamma-unsaturated alpha
      ketimino esters.
AB  - A highly enantioselective C2 Friedel-Crafts alkylation reaction of 3-substituted
      indoles to beta,gamma-unsaturated alpha-ketimino esters has been developed. This
      reaction was efficiently catalyzed by a chiral phosphoric acid catalyst. The
      corresponding C2-substituted indole derivatives, bearing an alpha-ketimino ester
      motif, were obtained in moderate to high yields (up to 93%) and with high
      enantioselectivities (up to >99% ee). 

PMID- 25594308
TI  - Dietary alpha-lactalbumin supplementation alleviates normocaloric western diet
      induced glucose intolerance in Gottingen minipigs.
AB  - OBJECTIVE: The pandemic of obesity in Western countries is mainly due to the high
      fat, high-energy diet prevailing there. Obesity-associated metabolic disorders
      are the consequence of fat mass increase leading to altered adipokine secretion,
      hyperlipemia, oxidant stress, low-grade inflammation, and eventually glucose
      intolerance. Yet not all people consuming a Western diet become obese, and the
      question is raised whether these people are also at risk of developing metabolic
      disorders. METHODS: Glucose tolerance, lipid profile, and oxidant and
      inflammation status were investigated longitudinally in lean Gottingen minipigs
      receiving for 16 weeks either a normal diet (ND), a Western diet (WD), or a
      Western diet supplemented with a whey protein isolate (WPI) rich in alpha
      lactalbumin known to improve glucose tolerance. ND and WD were supplied
      isoenergetically. RESULTS: Lean minipigs fed WD displayed glucose intolerance and
      altered lipid profile after 6 weeks of diet but no inflammation or oxidative
      stress. Supplementation with WPI alleviated glucose intolerance by improving
      insulin secretion, but not lipid profile. CONCLUSIONS: Western diet consumption
      is deleterious for glucose tolerance even in the absence of fat mass accretion,
      and dyslipemia is a major determinant for this metabolic dysfunction. Stimulating
      insulin secretion with a WPI is an effective strategy to improve glucose
      tolerance.

PMID- 25594309
TI  - Collaboration between hospital and primary care nurses: a literature review.
AB  - BACKGROUND: Nurses play an important role in the treatment and care of adults in
      both hospital and primary health care working within complex and fragmented
      organizational systems. As the nature of health care changes and hospital and
      primary care sectors become more closely associated, nurses in both sectors have
      an obligation to increase their collaboration. AIMS: This study aimed to increase
      the understanding of collaboration between nurses working with adults in hospital
      and primary health care, and to facilitate the future measurement of this
      collaboration. METHODS: A literature review was undertaken in July and August
      2013 using CINAHL and MEDLINE databases from the earliest to August 2013. The
      searches produced 4951 citations that were reduced to 22 articles for review
      using a four-step inclusion strategy. Inductive content analysis was used to
      analyse the data. RESULTS: It is suggested that collaboration is a process that
      contains (1) collaboration precursors: the opportunity to participate, knowledge
      and shared objectives; (2) elements of collaboration: competency, awareness and
      understanding of work roles and interaction; and (3) processes and outcomes: the
      events or behaviours that are the consequences of the collaboration between
      hospital and primary healthcare nurses. CONCLUSIONS: The results indicate that
      collaboration between hospital and primary healthcare nurses is an important and
      integral part of the work of nurses and a process consisting of several
      predictable issues leading to useful care outcomes. IMPLICATIONS FOR NURSING AND
      HEALTH POLICY: Current healthcare changes make it a requirement for hospital and
      primary healthcare nurses to collaborate when working with adults to continue to
      meet the needs of patients. The findings of this study can be used to improve
      collaboration in practice and to devise research to improve collaboration between
      hospital and primary healthcare nurses.

PMID- 25594311
TI  - Three-dimensional ordered ZnO/Cu2O nanoheterojunctions for efficient metal-oxide
      solar cells.
AB  - Interface modulation for broad-band light trapping and efficient carrier
      collection has always been the research focus in solar cells, which provides the
      most effective way to achieve performance enhancement. In this work, solution
      processed 3D ordered ZnO/Cu2O nanoheterojunctions, consisting of patterned n-ZnO
      nanorod arrays (NRAs) and p-Cu2O films, are elaborately designed and fabricated
      for the first time. By taking advantage of nanoheterojunctions with square
      patterned ZnO NRAs, solar cells demonstrate the maximum current density and
      efficiency of 9.89 mA cm(-2) and 1.52%, which are improved by 201% and 127%,
      respectively, compared to that of cells without pattern. Experimental analysis
      and theoretical simulation confirm that this exciting result originates from a
      more efficient broad-band light trapping and carrier collection of the 3D ordered
      ZnO/Cu2O nanoheterojunctions. Such 3D ordered nanostructures will have a great
      potential application for low-cost and all oxide solar energy conversion.
      Furthermore, the methodology applied in this work can be also generalized to
      rational design of other efficient nanodevices and nanosystems. 

PMID- 25594312
TI  - Metal-ion exchange, small-molecule sensing, selective dye adsorption, and
      reversible iodine uptake of three coordination polymers constructed by a new
      resorcin[4]arene-based tetracarboxylate.
AB  - By using a new resorcin[4]arene-based tetracarboxylate, three functional
      coordination polymers (CPs)--namely, [(CH3)2NH2][Cd2NaL(HCOO)2(HCOOH)(H2O)].H2O
      (1), [(CH3)2NH2]2[CdL].CH3OH.4H2O (2), and [(CH3)2NH2][Zn2Na3L2(H2O)2].H2O (3)-
      have been synthesized under solvothermal conditions (H4L = 2,8,14,20-tetra-pentyl
      4,10,16,22-tetrakis((4-carboxybenzyl)oxy)-6,12,18,24-tetra-methoxy
      resorcin[4]arene and DMF = N,N'-dimethylformamide). The structures of 1-3 have
      been confirmed by single-crystal X-ray diffraction analyses and further
      physically characterized. In 1, L and HCOO(-) link Cd(II) and Na(I) ions to yield
      an unusual three-dimensional (3D) 4-connected heterometallic framework with
      (4(2).6(4))(4.8(3).10.12) topology. In 2, L anions link Cd(II) ions to give a 3D
      binodal 4-connected framework with (4(2).6(3).8)2 topology. In 3, adjacent
      dodecanuclear heterometallic clusters are joined together by L anions, yielding a
      two-dimensional (2D) (3,8)-connected (3.4(2))(3(4).4(6).5(6).6(8).7(3).8)
      network. Most strikingly, CPs 1 and 2 display unusual metal-ion exchange
      characters. CP 2 shows remarkable reversible adsoption of I2 molecules. In
      addition, CPs 1-3 can selectively adsorb organic dyes and exhibit highly
      luminescent sensing properties for small molecules.

PMID- 25594313
TI  - In case you missed it: the Prenatal Diagnosis editors bring you the most
      significant advances of 2014.

PMID- 25594310
TI  - Rheb promotes cancer cell survival through p27Kip1-dependent activation of
      autophagy.
AB  - We previously found that the small GTPase Rheb regulates the cell-cycle inhibitor
      p27KIP1 (p27) in colon cancer cells by a mTORC1-independent mechanism. However,
      the biological function of the Rheb/p27 axis in cancer cells remains unknown.
      Here, we show that siRNA-mediated depletion of Rheb decreases survival of human
      colon cancer cells under serum deprivation. As autophagy can support cell
      survival, we analyzed the effect of Rheb on this process by detecting the
      modification of the autophagy marker protein LC3 by western blot and
      imunofluorescence. We found that Rheb promotes autophagy in several human cancer
      cell lines under serum deprivation. Accordingly, blocking autophagy inhibited the
      pro-survival effect of Rheb in colon cancer cells. We then analyzed whether p27
      was involved in the biological effect of Rheb. Depletion of p27 inhibited colon
      cancer cell survival, and Rheb induction of autophagy. These results suggest that
      p27 has an essential role in the effect of Rheb in response to serum deprivation.
      In addition, we demonstrated that the role of p27 in autophagy stands on the N
      terminal portion of the protein, where the CDK-inhibitory domain is located. Our
      results indicate that a Rheb/p27 axis accounts for the activation of autophagy
      that supports cancer cell survival. Our work therefore highlights a biological
      function of Rheb and prompts the need for future studies to address whether the
      mTORC1-independent Rheb/p27 axis could contribute to tumorigenesis and/or
      resistance to mTOR inhibitors.

PMID- 25594314
TI  - Adhesion and wetting of soft nanoparticles on textured surfaces: transition
      between Wenzel and Cassie-Baxter states.
AB  - We use a combination of the molecular dynamics simulations and scaling analysis
      to study interactions between gel-like nanoparticles and substrates covered with
      rectangular shape posts. Our simulations have shown that nanoparticles in contact
      with substrate undergo a first-order transition between the Cassie-Baxter and
      Wenzel states, which depends on nanoparticle shear modulus, the strength of
      nanoparticle-substrate interactions, height of the substrate posts, and
      nanoparticle size, Rp. There is a range of system parameters where these two
      states coexist such that the average indentation delta produced by substrate
      posts changes with nanoparticle shear modulus, Gp. We have developed a scaling
      model that describes deformation of nanoparticle in contact with patterned
      substrate. In the framework of this model, the effect of the patterned substrate
      can be taken into account by introducing an effective work of adhesion, Weff,
      which describes the first-order transition between Wenzel and Cassie-Baxter
      states. There are two different shape deformation regimes for nanoparticles with
      shear modulus Gp and surface tension gammap. The shape of small nanoparticles
      with size Rp < gammap(3/2)Gp(-1)Weff(-1/2) is controlled by capillary forces,
      while deformation of large nanoparticles, Rp > gammap(3/2)Gp(-1)Weff(-1/2), is
      determined by nanoparticle elastic and contact free energies. The model
      predictions are in good agreement with simulation results.

PMID- 25594315
TI  - Evolutionary genomics and HIV restriction factors.
AB  - PURPOSE OF REVIEW: To provide updated insights into innate antiviral immunity and
      highlight prototypical evolutionary features of well characterized HIV
      restriction factors. RECENT FINDINGS: Recently, a new HIV restriction factor,
      Myxovirus resistance 2, has been discovered and the region/residue responsible
      for its activity identified using an evolutionary approach. Furthermore, IFI16,
      an innate immunity protein known to sense several viruses, has been shown to
      contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA.
      SUMMARY: Restriction factors against HIV show characteristic signatures of
      positive selection. Different patterns of accelerated sequence evolution can
      distinguish antiviral strategies--offense or defence--as well as the level of
      specificity of the antiviral properties. Sequence analysis of primate orthologs
      of restriction factors serves to localize functional domains and sites
      responsible for antiviral action. We use recent discoveries to illustrate how
      evolutionary genomic analyses help identify new antiviral genes and their
      mechanisms of action.

PMID- 25594316
TI  - Mineralization of RDX-derived nitrogen to N2 via denitrification in coastal
      marine sediments.
AB  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a common constituent of military
      explosives. Despite RDX contamination at numerous U.S. military facilities and
      its mobility to aquatic systems, the fate of RDX in marine systems remains
      largely unknown. Here, we provide RDX mineralization pathways and rates in
      seawater and sediments, highlighting for the first time the importance of the
      denitrification pathway in determining the fate of RDX-derived N. (15)N nitro
      group labeled RDX ((15)N-[RDX], 50 atom %) was spiked into a mesocosm simulating
      shallow marine conditions of coastal Long Island Sound, and the (15)N enrichment
      of N2 (delta(15)N2) was monitored via gas bench isotope ratio mass spectrometry
      (GB-IRMS) for 21 days. The (15)N tracer data were used to model RDX
      mineralization within the context of the broader coastal marine N cycle using a
      multicompartment time-stepping model. Estimates of RDX mineralization rates based
      on the production and gas transfer of (15)N2O and (15)N2 ranged from 0.8 to 10.3
      MUmol d(-1). After 22 days, 11% of the added RDX had undergone mineralization,
      and 29% of the total removed RDX-N was identified as N2. These results
      demonstrate the important consideration of sediment microbial communities in
      management strategies addressing cleanup of contaminated coastal sites by
      military explosives. 

PMID- 25594317
TI  - A map for the future.

PMID- 25594318
TI  - Patients' perspectives on the brave new word 'deprescribing'.

PMID- 25594319
TI  - The health professionals' right to refuse: is it good, bad or ugly?

PMID- 25594320
TI  - The human area postrema: clear-cut silhouette and variations shown in vivo.
AB  - OBJECT The human area postrema (AP) is a circumventricular organ that has only
      been described in cadaveric specimens and animals. Because of its position in the
      calamus scriptorius and the absence of surface markers on the floor of the fourth
      ventricle, the AP cannot be clearly localized during surgical procedures. METHODS
      The authors intravenously administered 500 mg fluorescein sodium to 25 patients
      during neuroendoscopic procedures; in 12 of these patients they explored the
      fourth ventricle. A flexible endoscope equipped with dual observation modes for
      both white light and fluorescence was used. The intraoperative fluorescent images
      were reviewed and compared with anatomical specimens and 3D reconstructions.
      RESULTS Because the blood-brain barrier does not cover the AP, it was visualized
      in all cases after fluorescein sodium injection. The AP is seen as 2 coupled
      leaves on the floor of the fourth ventricle, diverging from the canalis centralis
      medullaris upward. Although the leaves normally appear short and thick, there can
      be different morphological patterns. Exploration using the endoscope's
      fluorescent mode allowed precise localization of the AP in all cases. CONCLUSIONS
      Fluorescence-enhanced inspection of the fourth ventricle accurately identifies
      the position of the AP, which is an important landmark during surgical procedures
      on the brainstem. A better understanding of the AP can also be valuable for
      neurologists, considering its functional role in the regulation of homeostasis,
      emesis, and cardiovascular and electrolyte balance. Despite the limited number of
      cases in this report, evidence indicates that the normal anatomical appearance of
      the AP is that of 2 short and thick leaves that are joined at the midline.
      However, there can be great variability in terms of the structure's shape and
      size. 

PMID- 25594321
TI  - Multisession stereotactic radiosurgery for large vestibular schwannomas.
AB  - OBJECT: Microsurgery is not the only option for larger vestibular schwannomas
      (VSs); recent reviews have confirmed the feasibility and efficacy of radiosurgery
      for larger VSs. This study illustrates the outcomes of a series of large VSs
      after multisession stereotactic radiosurgery (SRS). METHODS: A series of 33 VSs
      larger than 8 cm(3) (range 8-24 cm(3), mean 11 cm(3), median 9.4 cm(3)) were
      treated using the CyberKnife from 2003 to 2011 with the multisession SRS
      technique in 2-5 fractions (14-19.5 Gy). Five patients had undergone surgical
      removal and 5 had ventriculoperitoneal shunts. Nine patients were eligible for
      but refused surgery. Twelve patients were older than 70 years and 5 were younger
      than 40 years. Two female patients had neurofibromatosis. RESULTS: The follow-up
      period ranged from 12 to 111 months (median 48 months); radiological growth
      control was achieved in 94% of cases: 19 tumors (58%) displayed no size variation
      or reduction in tumor diameter; 12 (36%), after a transient enlargement,
      presented with arrested growth or shrinkage. Seven patients had a volume
      reduction of more than 50%. Two patients (6%) needed debulking and 2 were treated
      with ventriculoperitoneal shunts. Actuarial progressionfree survival rates at 1
      year and 5 years were 97% and 83%, respectively. Hearing was retained in 7 of the
      8 patients with serviceable baseline hearing. Adverse events were limited to 1
      case each of vertigo, tongue paresthesia, and trigeminal neuralgia. CONCLUSIONS:
      The good control rate obtained with multisession SRS deepens the controversy of
      the radiobiology of VSs and may extend the indication of radiation therapy
      (fractionated or SRS) for large VSs to include patients without symptoms of mass
      effect. The limited number of cases and short follow-up period do not provide
      sufficient support for widespread application of multisession SRS in young
      patients. Further studies with multisession SRS are warranted.

PMID- 25594323
TI  - Endoscopic endonasal resection of skull base chondrosarcomas: technique and early
      results.
AB  - OBJECT: The authors of this study sought to report the technique and early
      clinical outcomes of a purely endonasal endoscopic approach for resection of
      petroclival chondrosarcomas. METHODS: Between 2010 and 2014, 8 patients (4 men
      and 4 women) underwent endonasal endoscopic operations to resect petroclival
      chondrosarcomas at 2 institutions. The patients' mean age was 44.8 years (range
      30-64 years). One of the patients had previously undergone radiation therapy and
      another a staged craniotomy. Using volumetric software, an independent
      neuroradiologist assessed the extent of the resections on MRI scans taken
      immediately after surgery and at the 3-month follow-up. Immediate complications
      and control of symptoms were also recorded. In addition, the authors reviewed the
      current literature on surgical treatment of chondrosarcoma. RESULTS: The mean
      preoperative tumor diameter and volume were 3.4 cm and 9.8 cm(3), respectively.
      Six patients presented with cranial neuropathies. Endonasal endoscopic surgery
      achieved > 95% resection in 5 of the 8 patients and < 95% resection in the
      remaining 3 patients. One of the 6 neuropathies resolved, and the remaining 5
      partially improved. One instance of postoperative CSF leakage required a
      reoperation for repair; no other complications associated with these operations
      were observed. All of the patients underwent adjuvant radiotherapy. CONCLUSIONS:
      According to the authors' experience, the endoscopic endonasal route is a safe
      and effective approach for the resection of appropriately selected petroclival
      chondrosarcomas.

PMID- 25594322
TI  - Letter to the editor: Readmission.

PMID- 25594324
TI  - Giant intracranial epidermoids: is total removal feasible?
AB  - OBJECT: Epidermoid tumors arise from misplaced squamous epithelium and enlarge
      through the accumulation of desquamated cell debris. Optimal treatment consists
      of total removal of the capsule; therefore, giant and multicompartmental tumors
      are particularly challenging. A conservative attitude in handling the tumor
      capsule is common given concerns about capsule adherence to neurovascular
      structures, and thus the possibility of recurrence is accepted with the intent of
      minimizing complications. This study focuses on the outcome of surgery in
      patients with giant epidermoid tumors for which total capsule removal was the
      aim. METHODS: The authors conducted a retrospective analysis of all patients with
      giant epidermoid tumors treated by the senior author (O.A.), who pursued total
      removal of the capsule through skull base approaches. Patients were divided into
      2 groups: one including patients with de novo tumors and the other consisting of
      patients who presented with recurrent tumors. RESULTS: Thirty-four patients had
      undergone 46 operations, and the senior author performed 38 of these operations
      in the study period. The average tumor dimensions were 55 * 36 mm, and 25 tumors
      had multicompartmental extensions. Total removal of the tumor and capsule was
      achieved with the aid of the microscope in 73% of the 26 de novo cases but in
      only 17% of the 12 recurrent tumor cases. The average follow-up among all
      patients was 111 months (range 10-480 months), and the average postsurgical
      follow-up was 56.8 months (range 6-137 months). There were 4 recurrences in the
      de novo group, and every case had had a small piece of tumor capsule left behind.
      One patient died after delayed rupture of a pseudoaneurysm. In the de novo group,
      the average preoperative Karnofsky Performance Scale (KPS) score was 71.42%,
      which improved to 87.14% on long-term follow-up. In the group with recurrences,
      the KPS score also improved on long-term follow-up, from 64.54% to 84.54%. In the
      de novo group, 3 cases (11.5%) had permanent cranial nerve deficits, and 4 cases
      (15.4%) had a CSF leak. In the recurrence group, 3 cases (25%) had new, permanent
      cranial nerve deficits, and 1 (8.3%) had a CSF leak. Two patients in this group
      developed hydrocephalus and required a shunt. CONCLUSIONS: Total removal of the
      capsule of giant epidermoid tumors was achieved in 73% of patients with de novo
      tumors and was associated with improved function, low morbidity and mortality,
      and a lower risk of recurrence. Surgery in patients with recurrent tumors was
      associated with higher morbidity and persistence of the disease.

PMID- 25594325
TI  - Accuracy of direct magnetic resonance imaging-guided placement of drug infusion
      cannulae.
AB  - An intraoperative MRI (iMRI)-compatible system has been developed for direct
      placement of convection-enhanced delivery (CED) cannulae using real-time imaging.
      To establish the precision and feasibility of this technology, the authors
      analyzed findings in patients who underwent direct iMRI CED cannula placement.
      Three consecutive patients underwent iMRI-guided placement of CED infusion
      cannulae (6 cannulae) for treatment of diffuse intrinsic brainstem glioma (2
      patients) or Parkinson's disease (1 patient). Convective infusion cannulae were
      guided to the target using the ClearPoint iMRI-based navigation platform (MRI
      Interventions, Inc.). Placement accuracy was analyzed. Real-time iMRI during
      infusion cannula insertion allowed for monitoring of trajectory accuracy during
      placement. During cannula insertion, no reinsertions or changes due to errors in
      targeting were necessary. The mean radial error was 1.0 +/- 0.5 mm (+/- SD).
      There was no correlation between the total length of the planned trajectory and
      the radial error (Pearson's coefficient: -0.40; p = 0.5). The mean
      anteroposterior and lateral errors were 0.9 +/- 0.5 and 0.3 +/- 0.2 mm,
      respectively. The mean in-plane distance error was 1.0 +/- 0.4 mm. The mean tip
      error (scalar distance between the planned target and actual tip) was 1.9 +/- 0.9
      mm. There was no correlation between the length of the planned trajectory and any
      of the measured errors. No complications were associated with cannula placement.
      Real-time iMRI-based targeting and monitoring of infusion cannula placement is a
      safe, effective, and accurate technique that should enable more selective
      perfusion of brain regions. 

PMID- 25594327
TI  - Role of adjuvant or salvage radiosurgery in the management of unresected residual
      or progressive glioblastoma multiforme in the pre-bevacizumab era.
AB  - OBJECT: After initial standard of care management of glioblastoma multiforme
      (GBM), relatively few proven options remain for patients with unresected
      progressive tumor. Numerous reports describe the value of radiosurgery, yet this
      modality appears to remain underutilized. The authors analyzed the outcomes of
      early adjuvant stereotactic radiosurgery (SRS) for unresected tumor or later
      salvage SRS for progressive GBM. Radiosurgery was performed as part of the
      multimodality management and was combined with other therapies. Patients
      continued to receive additional chemotherapy after SRS and prior to progression
      being documented. In this retrospective analysis, the authors evaluated factors
      that affected patient overall survival (OS) and progression-free survival.
      METHODS: Between 1987 and 2008 the authors performed Gamma Knife SRS in 297
      patients with histologically proven GBMs. All patients had received prior
      fractionated radiation therapy, and 66% had undergone one or more chemotherapy
      regimens. Ninety-six patients with deep-seated unresectable GBMs underwent biopsy
      only. Of those in whom excision had been possible, resection was considered to be
      gross total in 68 and subtotal in 133. The median patient age was 58 years (range
      23-89 years) and the median tumor volume was 14 cm(3) (range 0.26-84.2 cm(3)).
      The median prescription dose delivered to the imaging-defined tumor margin was 15
      Gy (range 9-25 Gy). The median follow-up duration was 8.6 months (range 1.1-173
      months). Cox regression models were used to analyze survival outcomes. Variables
      examined included age, residual versus recurrent tumor, prior chemotherapy, time
      to first recurrence, SRS dose, and gross tumor volume. RESULTS: The median
      survival times after radiosurgery and after diagnosis were 9.03 and 18.1 months,
      respectively. The 1-year and 2-year OS after SRS were 37.9% and 16.7%,
      respectively. The 1-year and 2-year OS after diagnosis were 76.2% and 30.8%,
      respectively. Using multivariate analysis, factors associated with improved OS
      after diagnosis were younger age (< 60 years) at diagnosis (p < 0.0001), tumor
      volume < 14 cm(3) (p < 0.001), use of prior chemotherapy (p = 0.001), and
      radiosurgery at the time of recurrence (p < 0.0001). Multivariate analysis showed
      that younger age (p < 0.0001) and smaller tumor volume (< 14 cm(3)) (p = 0.001)
      were significantly associated with increased OS after SRS. Adverse radiation
      effects were seen in 69 patients (23%). Fifty-eight patients (19.5%) underwent
      additional resection after SRS. The median survivals after diagnosis for
      recursive partitioning analysis Classes III, IV and V+VI were 31.6, 20.8, and
      16.7 months, respectively. CONCLUSIONS: In this analysis 30% of a heterogeneous
      cohort of GBM patients eligible for SRS had an OS of 2 years. Radiosurgery at the
      time of tumor progression was associated with a median survival of 21.8 months.
      The role of radiosurgery for GBMs remains controversial. The findings in this
      study support the need for a funded and appropriately designed clinical trial
      that will provide a higher level of evidence regarding the future role of SRS for
      glioblastoma patients in whom disease has progressed despite standard management.

PMID- 25594328
TI  - Spectral and thermal characterization of halogen-bonded novel crystalline oligo(p
      bromoacetophenone formaldehyde).
AB  - A novel oligomer p-bromoacetophenone-formaldehyde (OPBAF) was prepared by
      condensation polymerization in the presence of an acid as catalyst. It was
      characterized by FT-IR, NMR, pyrolysis GC/MS, XRD, GPC, and TG-DTG. The
      crystallographic parameters and space group for hexagonal OPBAF were a = b =
      2.0810 A and c = 9.2340 A and P3m1, respectively. The degradation activation
      energy of the oligomer was studied by the Kissinger method. The kinetic
      parameters were also obtained. Halogen bonding interactions in the crystalline
      oligomers are identified between halogen...carbonyl and halogen...halogen. Little
      correlation was found in the halogen bonding motifs exhibited as a function of
      bromine present in this oligomer, and a unique bifurcated Br...Br/Br...O?C
      halogen bonding synthon was identified. This newly developed oligomer may be used
      as an interesting material for the development of 3D-designed structural
      products. 

PMID- 25594329
TI  - Lathyrus hirsutus (Caley Pea) intoxication in a herd of horses.
AB  - BACKGROUND: Caley Pea (Lathyrus hirsutus) is potentially toxic to horses, but
      large case series are not reported. OBJECTIVES: To describe the clinical signs of
      horses intoxicated with Lathyrus hirsutus and speculate on the neuroanatomical
      lesion localization and pathogenesis based upon the observed clinical signs.
      ANIMALS: Twenty-two of 25 horses ranging in age from 6 to 34 months were
      affected. Five affected horses were presented to the OSUCHVS for evaluation and
      treatment after having been attended at the ranch by a local veterinarian (ALA).
      An additional horse that had been euthanized was also presented for necropsy.
      METHODS: A case series is presented. Diagnostic evaluation included: physical
      examination, complete blood count, serum biochemistry, CSF analysis, EMG, ERG,
      upper airway endoscopy, muscle biopsy, and serum vitamin E analysis. The grain
      ration consumed by the affected horses was analyzed for ionophores and cultured
      for fungi: the hay was examined for toxic plants. RESULTS: Bermuda grass hay
      consumed by the horses contained large quantities of mature Lathyrus hirsutus.
      Acute clinical signs conform to earlier descriptions of Lathyrus hirsutus
      intoxication in cattle. Residual neurologic signs were characterized by
      incoordination in the rhythmicity of multiple gaits. Evidence of mild neurogenic
      muscle atrophy was recognized in 1 of 5 horses biopsied. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Caley Pea intoxication may occur within days of seed pod consumption.
      The neurologic signs are unique and suggest involvement of the upper motor neuron
      system and regions of the spinal cord influencing voluntary motor movement.
      Drought conditions during plant growth may increase the risk of toxicosis.

PMID- 25594330
TI  - The elusiveness of population-wide high blood pressure control.
AB  - High blood pressure (hypertension) is a leading risk factor for cardiovascular
      disease. It is highly prevalent in the US general population, especially in those
      who are old, African American, or socially disadvantaged. Prevalence is also high
      and increasing worldwide. Awareness, treatment, and control of hypertension have
      improved over time, but there is still considerable room for improvement. The
      optimal solution to this health challenge varies by country. Several
      nonpharmacologic and pharmacologic interventions are well proven as effective
      means to prevent hypertension and improve control rates in those with established
      hypertension. Better prevention and control of hypertension will yield
      substantial general population health benefits and remain high priorities in
      public health. 

PMID- 25594331
TI  - Has epidemiology become infatuated with methods? A historical perspective on the
      place of methods during the classical (1945-1965) phase of epidemiology.
AB  - Before World War II, epidemiology was a small discipline, practiced by a handful
      of people working mostly in the United Kingdom and in the United States. Today it
      is practiced by tens of thousands of people on all continents. Between 1945 and
      1965, during what is known as its "classical" phase, epidemiology became
      recognized as a major academic discipline in medicine and public health. On the
      basis of a review of the historical evidence, this article examines to which
      extent classical epidemiology has been a golden age of an action-driven, problem
      solving science, in which epidemiologists were less concerned with the
      sophistication of their methods than with the societal consequences of their
      work. It also discusses whether the paucity of methods stymied or boosted
      classical epidemiology's ability to convince political and financial agencies
      about the need to intervene in order to improve the health of the people. 

PMID- 25594326
TI  - Effect of exosomes derived from multipluripotent mesenchymal stromal cells on
      functional recovery and neurovascular plasticity in rats after traumatic brain
      injury.
AB  - OBJECT: Transplanted multipotent mesenchymal stromal cells (MSCs) improve
      functional recovery in rats after traumatic brain injury (TBI). In this study the
      authors tested a novel hypothesis that systemic administration of cell-free
      exosomes generated from MSCs promotes functional recovery and neurovascular
      remodeling in rats after TBI. METHODS: Two groups of 8 Wistar rats were subjected
      to TBI, followed 24 hours later by tail vein injection of 100 MUg protein of
      exosomes derived from MSCs or an equal volume of vehicle (phosphate-buffered
      saline). A third group of 8 rats was used as sham-injured, sham-treated controls.
      To evaluate cognitive and sensorimotor functional recovery, the modified Morris
      water maze, modified Neurological Severity Score, and foot-fault tests were
      performed. Animals were killed at 35 days after TBI. Histopathological and
      immunohistochemical analyses were performed for measurements of lesion volume,
      neurovascular remodeling (angiogenesis and neurogenesis), and neuroinflammation.
      RESULTS: Compared with the saline-treated group, exosome-treated rats with TBI
      showed significant improvement in spatial learning at 34-35 days as measured by
      the modified Morris water maze test (p < 0.05), and sensorimotor functional
      recovery (i.e., reduced neurological deficits and foot-fault frequency) was
      observed at 14-35 days postinjury (p < 0.05). Exosome treatment significantly
      increased the number of newly generated endothelial cells in the lesion boundary
      zone and dentate gyrus and significantly increased the number of newly formed
      immature and mature neurons in the dentate gyrus as well as reducing
      neuroinflammation. CONCLUSIONS: The authors demonstrate for the first time that
      MSC-generated exosomes effectively improve functional recovery, at least in part,
      by promoting endogenous angiogenesis and neurogenesis and by reducing
      inflammation in rats after TBI. Thus, MSC-generated exosomes may provide a novel
      cell-free therapy for TBI and possibly for other neurological diseases.

PMID- 25594332
TI  - Attitudes of significant others of people with Meniere's disease vary from coping
      to victimization.
AB  - OBJECTIVE: To explore the impact, reactions and coping methods of the significant
      others (SOs) of people with Meniere's disease (MD). DESIGN: SOs of people with MD
      were asked to answer open-ended questions reporting the 'life effects' and
      'positive experiences' they have had as a result of the partner's condition. The
      replies to the 'life effects' question was categorized using the WHO-ICF
      framework. The responses of 'life effects' from this study and the 'positive
      experiences' reported in a recent study ( Manchaiah et al, 2013 ) were evaluated
      with K-means clustering analysis. STUDY SAMPLE: Eighty-eight SOs (42 male, 42
      female, and four did not state gender). RESULTS: While the SOs mainly listed
      their own problems, a significant number of responses related to the problems of
      their partner. Personal perspectives tended to focus on the consequences of their
      partner's condition, whereas in perspectives of their partner they focussed on
      his/her symptoms. Further, replies from 81 SOs were used in evaluation of
      responses and were classified into four categories: constrained life attitude;
      disease burden attitude; care and support attitude; and social isolation
      attitude. CONCLUSIONS: The results of this study support the importance of
      including the SO of people with MD in the rehabilitation process.

PMID- 25594333
TI  - A survey of the nature of trauma of post-traumatic benign paroxysmal positional
      vertigo.
AB  - OBJECTIVE: A clinical description of post-traumatic benign paroxysmal positional
      vertigo (t-BPPV) in a large cohort is reported, sometimes caused by apparently
      insignificant minor head traumas. The aim of the study was to carefully assess
      the prevalence of t-BPPV and the main outcomes belonging to specific traumatic
      events. DESIGN: Retrospective analysis of medical records of t-BPPV cases among
      patients suffering from BPPV. STUDY SAMPLE: Among 3060 patients with a clinical
      diagnosis of BPPV, we reviewed 716 clinical cases in which a clear association to
      a traumatic event was present. RESULTS: A traumatic event was identified in 23.4%
      of total enrolled BPPV patients. Some minor head traumas could be more prone to
      determine BPPV in females. We confirmed that t-BPPV appeared significantly more
      difficult to treat than idiopathic form. Posterior canal t-BPPV cases required
      more treatment sessions before obtaining therapeutic success, while horizontal
      ones recovered at most after two repositioning maneuvers. CONCLUSION: Post
      traumatic BPPV is considered one of the most common known etiologies. An accurate
      understanding of trauma mechanism, gender prevalence, and therapeutic success
      rates of each event, could be useful in adequately treating and planning follow
      up examinations.

PMID- 25594334
TI  - Rasch analysis of the 23-item version of the Roland Morris Disability
      Questionnaire.
AB  - OBJECTIVE: To determine the psychometric properties of the 23-item version of the
      Roland Morris Disability Questionnaire (RMDQ-23) and to quantify their stability
      across 2 cultures/languages and 2 types of care-settings. METHODS: Rasch analysis
      of data from 1,000 patients with low back pain from primary care (UK and Denmark)
      and secondary care (Denmark). RESULTS: The RMDQ-23 is unidimensional if local
      item dependency issues are accommodated, but contains several misfitting or
      overdiscriminating items, some poor targeting of items, and the scoring of 4-5
      items is differentially affected by common clinical characteristics (such as age,
      gender, pain intensity, pain duration and care setting), depending on the
      country. CONCLUSION: As similar results have been found for the RMDQ-24, we
      believe it is timely to reconsider whether: (i) the RMDQ should be reconstructed
      using an item-response theory-based approach that includes consideration of new
      items and response options; or (ii) the use of alternative questionnaires should
      be recommended, such as the Oswestry Disability Index, that have shown evidence
      of fitting the Rasch model; or (iii) a completely new condition-specific
      questionnaire should be developed, perhaps utilizing a computerized adaptive
      testing platform.

PMID- 25594335
TI  - Development and evaluation of a loop-mediated isothermal amplification assay for
      the detection of channel catfish virus.

PMID- 25594336
TI  - How we made professionalism relevant to twenty-first century residents.
AB  - The complexity of the current medical trainee work environment, including the
      impact of social media participation, is underappreciated. Despite rapid adoption
      of social media by residents and the introduction of social media guidelines
      targeted at medical professionals, there is a paucity of data evaluating
      practical methods to incorporate social media into professionalism teaching
      curricula. We developed a flipped classroom program, focusing on the application
      of professionalism principles to challenging real-life scenarios including social
      media-related issues. The pre-workshop evaluation showed that the participants
      had a good understanding of basic professionalism concepts. A post-workshop
      survey assessed residents' comfort level with professionalism concepts. The post
      workshop survey revealed that the postgraduate trainees perceived significant
      improvement in their understanding of professionalism (p < 0.05). Resident
      responses also exposed some challenges of real-life clinical settings. There was
      an apparent contradiction between placing a high value on personal health and
      believing that physicians ought to be available to patients at any time.
      Participants' satisfaction with the course bodes well for continual modification
      of such courses. Innovative flipped classroom format in combination with
      simulation-based sessions allows easy incorporation of contemporary
      professionalism issues surrounding social media. 

PMID- 25594337
TI  - Highly efficient photothermal effect by atomic-thickness confinement in two
      dimensional ZrNCl nanosheets.
AB  - We report a giant photothermal effect arising from quantum confinement in two
      dimensional nanomaterials. ZrNCl ultrathin nanosheets with less than four
      monolayers of graphene-like nanomaterial successfully generated synergetic
      effects of larger relaxation energy of photon-generated electrons and intensified
      vibration of surface bonds, offering predominantly an enhancement of the electron
      phonon interaction to a maximized extent. As a result, they could generate heat
      flow reaching an ultrahigh value of 5.25 W/g under UV illumination with
      conversion efficiency up to 72%. We anticipate that enhanced electron-phonon
      coupling in a quantum confinement system will be a powerful tool for optimizing
      photothermal conversion of inorganic semiconductors. 

PMID- 25594338
TI  - Small bowel patency assessment using the patency device and a novel targeted
      (limited radiation) computed tomography-based protocol.
AB  - BACKGROUND AND AIM: Excretion of the patency capsule (PC) within a certain time
      frame may be used to demonstrate luminal patency prior to capsule endoscopy (CE).
      We aimed to determine how often further radiological imaging is needed to confirm
      luminal patency after PC, assess radiologists' ability to locate the PC on plain
      abdominal films, and evaluate the outcomes of a novel computed tomography (CT)
      protocol for PC localization. METHODS: A study of the ability of radiologists to
      localize PC using plain abdominal films was performed. A novel protocol targeting
      a limited CT at the level of the PC identified on the "scout" film if retained 30
      h post-ingestion was prospectively evaluated in 400 consecutive patients
      undergoing PC. RESULTS: In a study of the confidence with which radiologists
      could localize the PC on plain films, radiologists preferred abdominal CT to
      localize PCs identified on plain films in 74% of cases. In a protocol based on
      the use of a PC and targeted, limited CT scan to confirm small bowel patency in
      those failing to excrete the PC 30 h post-ingestion, the sensitivity,
      specificity, positive, and negative predictive value were 99.4%, 90.0%, 99.7%,
      and 81.0%, respectively. Crohn's disease was the only statistically significant
      predictor associated with higher risk of luminal stricture (P=0.001) in post-hoc
      analysis. CONCLUSIONS: Excretion of the PC 30 h post-ingestion reliably predicts
      safe CE passage. Plain abdominal radiology is unreliable and a scout film
      targeted, limited CT scan offers an accurate minimal radiation method of
      determining small bowel patency.

PMID- 25594339
TI  - Two New Species of Zoothamnium (Ciliophora, Peritrichia) from Korea, with New
      Observations of Z. parahentscheli Sun et al., 2009.
AB  - Three peritrichous ciliates, Zoothamnium arcuatum n. sp., Z. grossi n. sp., and
      Z. parahentscheli Sun et al., 2009, were collected from an estuary of the
      Taehwagang River, Korea. All these species were investigated based on live
      observations and silver staining, and their small subunit (SSU) rRNA gene was
      also sequenced. Zoothamnium arcuatum can be identified by a goblet-shaped colony,
      double-layered peristomial lip, and abstomally shortened row 3 of infundibular
      polykinety 3 (P3). Zoothamnium grossi is morphologically characterized by an
      alternately branched stalk with the lowest secondary stalk diverging from the
      main part of colony, asymmetrically bell-shaped zooids, and three short, parallel
      ciliary rows in P3. Phylogenetic analysis revealed that the three Zoothamnium
      species described in this paper clustered with other members of the family
      Zoothamniidae, as expected.

PMID- 25594340
TI  - Preparation and application of crosslinked poly(sodium acrylate)--coated
      magnetite nanoparticles as corrosion inhibitors for carbon steel alloy.
AB  - This work presents a new method to prepare poly(sodium acrylate) magnetite
      composite nanoparticles. Core/shell type magnetite nanocomposites were
      synthesized using sodium acrylate as monomer and N,N-methylenebisacrylamide (MBA)
      as crosslinker. Microemulsion polymerization was used for constructing core/shell
      structures with magnetite nanoparticles as core and poly(sodium acrylate) as
      shell. Fourier transform infrared spectroscopy (FTIR) was employed to
      characterize the nanocomposite chemical structure. Transmittance electron
      microscopy (TEM) was used to examine the morphology of the modified poly(sodium
      acrylate) magnetite composite nanoparticles. These particle will be evaluated for
      effective anticorrosion behavior as a hydrophobic surface on stainless steel. The
      composite nanoparticles has been designed by dispersing nanocomposites which act
      as a corrosion inhibitor. The inhibition effect of AA-Na/magnetite composites on
      steel corrosion in 1 M HCl solution was investigated using potentiodynamic
      polarization curves and electrochemical impedance spectroscopy (EIS).
      Polarization measurements indicated that the studied inhibitor acts as mixed type
      corrosion inhibitor. EIS spectra exhibit one capacitive loop. The different
      techniques confirmed that the inhibition efficiency reaches 99% at 50 ppm
      concentration. This study has led to a better understanding of active
      anticorrosive magnetite nanoparticles with embedded nanocomposites and the
      factors influencing their anticorrosion performance. 

PMID- 25594341
TI  - TDAE strategy in the benzoxazolone series: synthesis and reactivity of a new
      benzoxazolinonic anion.
AB  - We describe an original pathway to produce new 5-substituted 3-methyl-6-nitro
      benzoxazolones by the reaction of aromatic carbonyl and alpha-carbonyl ester
      derivatives with a benzoxazolinonic anion formed exclusively via the TDAE
      strategy. 

PMID- 25594342
TI  - Bisdemethoxycurcumin Induces apoptosis in activated hepatic stellate cells via
      cannabinoid receptor 2.
AB  - Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver,
      undergo apoptosis when liver injuries cease, which may contribute to the
      resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of
      curcumin with anti-inflammatory and anti-cancer activities. The therapeutic
      potential of BDMC in hepatic fibrosis has not been studied thus far in the
      context of the apoptosis in activated HSCs. In the current study, we compared the
      activities of BDMC and curcumin in the HSC-T6 cell line and demonstrated that
      BDMC relatively induced a potent apoptosis. BDMC-induced apoptosis was mediated
      by a combinatory inhibition of cytoprotective proteins, such as Bcl2 and heme
      oxygenase-1 and increased generation of reactive oxygen species. Intriguingly,
      BDMC-induced apoptosis was reversed with co-treatment of sr144528, a cannabinoid
      receptor (CBR) 2 antagonist, which was confirmed with genetic downregulation of
      the receptor using siCBR2. Additionally, incubation with BDMC increased the
      formation of death-induced signaling complex in HSC-T6 cells. Treatment with BDMC
      significantly diminished total intracellular ATP levels and upregulated ATP
      inhibitory factor-1. Collectively, the results demonstrate that BDMC induces
      apoptosis in activated HSCs, but not in hepatocytes, by impairing cellular
      energetics and causing a downregulation of cytoprotective proteins, likely
      through a mechanism that involves CBR2. 

PMID- 25594343
TI  - Ginsenoside Rc promotes anti-adipogenic activity on 3T3-L1 adipocytes by down
      regulating C/EBPalpha and PPARgamma.
AB  - Panax ginseng and its major components, the ginsenosides, are widely used in
      oriental medicine for the prevention of various disorders. In the present study,
      the inhibitory activity of ginsenoside Rc on adipogenesis was investigated using
      the 3T3-L1 cell line. The results obtained showed that Rc reduced the
      proliferation and viability of 3T3-L1 preadipocytes in a dose-dependent manner.
      Treatment with Rc decreased the number of adipocytes and reduced lipid
      accumulation in maturing 3T3-L1 preadipocytes, demonstrating an inhibitory effect
      on lipogenesis. Moreover, it was found that Rc directly induced lipolysis in
      adipocytes and down-regulated the expression of major transcription factors of
      the adipogenesis pathway, such as PPARgamma and C/EBPalpha. These findings
      indicate that Rc is capable of suppressing adipogenesis and therefore they seem
      to be natural bioactive factors effective in adipose tissue mass modulation. 

PMID- 25594344
TI  - Synthesis and evaluation of paeonol derivatives as potential multifunctional
      agents for the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder
      characterized by memory loss, language impairment, personality changes and
      intellectual decline. Taking into account the key pathological features of AD,
      such as low levels of acetylcholine, beta-amyloid (Abeta) aggregation, oxidative
      stress and dyshomeostasis of biometals, a new series of paeonol derivatives 5a-5d
      merging three different functions, i.e., antioxidant, anti-acetylcholinesterase
      (AChE) activity, metal chelating agents for AD treatment have been synthesized
      and characterized. Biological assays revealed that compared with paeonol (309.7
      MUM), 5a-5d had a lower DPPH IC50 value (142.8-191.6 MUM). 5a-5d could
      significantly inhibit hydrogen peroxide-induced neuronal PC12 cell death assessed
      by MTT assay in the concentration range of 5-40 MUM. AChE activity was
      effectively inhibited by 5a-5d, with IC50 values in the range of 0.61-7.04 MUM.
      5a-5d also exhibited good metal-chelating ability. All the above results
      suggested that paeonol derivatives may be promising multifunctional agents for AD
      treatment. 

PMID- 25594345
TI  - The viability of photocatalysis for air purification.
AB  - Photocatalytic oxidation (PCO) air purification technology is reviewed based on
      the decades of research conducted by the United Technologies Research Center
      (UTRC) and their external colleagues. UTRC conducted basic research on the
      reaction rates of various volatile organic compounds (VOCs). The knowledge gained
      allowed validation of 1D and 3D prototype reactor models that guided further
      purifier development. Colleagues worldwide validated purifier prototypes in
      simulated realistic indoor environments. Prototype products were deployed in
      office environments both in the United States and France. As a result of these
      validation studies, it was discovered that both catalyst lifetime and byproduct
      formation are barriers to implementing this technology. Research is ongoing at
      the University of Connecticut that is applicable to extending catalyst lifetime,
      increasing catalyst efficiency and extending activation wavelength from the
      ultraviolet to the visible wavelengths. It is critical that catalyst lifetime is
      extended to realize cost effective implementation of PCO air purification. 

PMID- 25594346
TI  - Synthesis and cytotoxicity evaluation of some novel thiazoles, thiadiazoles, and
      pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones incorporating triazole
      moiety.
AB  - Reactions of hydrazonoyl halides and each of methyl 2-(1-(5-methyl-1-phenyl-1H
      1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbodithioate and 2-(1-(5-methyl-1
      phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbothioamide afforded 2-(1
      (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-3-phenyl-5
      substituted-2,3-dihydro-1,3,4-thiadiazoles and 5-(4-substituted)diazenyl)-2-(2-(1
      (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-arylthiazoles,
      respectively. Analogously, the reactions of hydrazonoyl halides with 7-(5-methyl
      1-phenyl-1H-1,2,3-triazol-4-yl)-5-phenyl-2-thioxo-2,3-dihydropyrido[2,3
      d]pyrimidin-4(1H)-one gave 3-(4-substituted)-8-(5-methyl-1-phenyl-1H-1,2,3
      triazol-4-yl)-6-phenyl-1-arylpyrido[2,3-d]-[1,2,4]-triazolo-[4,3-a]pyrimidin-
      5(1H)-ones in a good yield. The structures of the newly synthesized were
      elucidated via elemental analysis, spectral data and alternative synthesis routes
      whenever possible. Twelve of the newly synthesized compounds have been evaluated
      for their antitumor activity against human breast carcinoma (MCF-7) and human
      hepatocellular carcinoma (HepG2) cell lines. Their structure activity
      relationships (SAR) were also studied. The 1,3,4-thiadiazole derivative 9b (IC50
      = 2.94 uM) has promising antitumor activity against the human hepatocellular
      carcinoma cell line and the thiazole derivative 12a has promising inhibitory
      activity against both the human hepatocellular carcinoma cell line and the breast
      carcinoma cell line (IC50 = 1.19, and 3.4 uM, respectively). 

PMID- 25594347
TI  - Beyond the excluded volume effects: mechanistic complexity of the crowded milieu.
AB  - Macromolecular crowding is known to affect protein folding, binding of small
      molecules, interaction with nucleic acids, enzymatic activity, protein-protein
      interactions, and protein aggregation. Although for a long time it was believed
      that the major mechanism of the action of crowded environments on structure,
      folding, thermodynamics, and function of a protein can be described in terms of
      the excluded volume effects, it is getting clear now that other factors
      originating from the presence of high concentrations of "inert" macromolecules in
      crowded solution should definitely be taken into account to draw a more complete
      picture of a protein in a crowded milieu. This review shows that in addition to
      the excluded volume effects important players of the crowded environments are
      viscosity, perturbed diffusion, direct physical interactions between the crowding
      agents and proteins, soft interactions, and, most importantly, the effects of
      crowders on solvent properties. 

PMID- 25594348
TI  - Possible roles of plant sulfurtransferases in detoxification of cyanide, reactive
      oxygen species, selected heavy metals and arsenate.
AB  - Plants and animals have evolved various potential mechanisms to surmount the
      adverse effects of heavy metal toxicity. Plants possess low molecular weight
      compounds containing sulfhydryl groups (-SH) that actively react with toxic
      metals. For instance, glutathione (gamma-Glu-Cys-Gly) is a sulfur-containing
      tripeptide thiol and a substrate of cysteine-rich phytochelatins (gamma-Glu-Cys)2
      11-Gly (PCs). Phytochelatins react with heavy metal ions by glutathione S
      transferase in the cytosol and afterwards they are sequestered into the vacuole
      for degradation. Furthermore, heavy metals induce reactive oxygen species (ROS),
      which directly or indirectly influence metabolic processes. Reduced glutathione
      (GSH) attributes as an antioxidant and participates to control ROS during stress.
      Maintenance of the GSH/GSSG ratio is important for cellular redox balance, which
      is crucial for the survival of the plants. In this context, sulfurtransferases
      (Str), also called rhodaneses, comprise a group of enzymes widely distributed in
      all phyla, paving the way for the transfer of a sulfur atom from suitable sulfur
      donors to nucleophilic sulfur acceptors, at least in vitro. The best
      characterized in vitro reaction is the transfer of a sulfane sulfur atom from
      thiosulfate to cyanide, leading to the formation of sulfite and thiocyanate.
      Plants as well as other organisms have multi-protein families (MPF) of Str.
      Despite the presence of Str activities in many living organisms, their
      physiological role has not been clarified unambiguously. In mammals, these
      proteins are involved in the elimination of cyanide released from cyanogenic
      compounds. However, their ubiquity suggests additional physiological functions.
      Furthermore, it is speculated that a member of the Str family acts as arsenate
      reductase (AR) and is involved in arsenate detoxification. In summary, the role
      of Str in detoxification processes is still not well understood but seems to be a
      major function in the organism. 

PMID- 25594349
TI  - An alkaloid and a steroid from the endophytic fungus Aspergillus fumigatus.
AB  - Two new compounds, fumitremorgin 12-methoxy-13-[5'-hydroxy-2'-(1''-hydroxy-3''
      methoxy-5''-methylbenzoyl)-3'-methoxy]benzoic acid methyl ester (fumitremorgin D,
      1) and 4,8,10,14-tetramethyl-6-acetoxy-14-[16-acetoxy-19-(20,21-dimethyl)-18-ene]
      phenanthrene-1-ene-3,7-dione (2) were isolated from the cultured endophytic
      isolated fungus Aspergillus fumigatus, together with fourteen known compounds.
      Their structures were elucidated by 1-D and 2-D NMR analyses. The cytotoxicity
      profile of the compound against the human hepatocellular carcinoma cell line
      HepG2 was evaluated by MTT antiproliferative assays. 

PMID- 25594350
TI  - The impact of a rural scanner in overcoming urban versus rural disparities in the
      utilisation of computed tomography.
AB  - OBJECTIVE: In 2008, Oamaru Hospital became the second rural hospital in New
      Zealand to install a computed tomography (CT) scanner. This article assesses the
      impact of this on local CT scanning rates. DESIGN: Observational: review of
      radiology department data. SETTING: Rural hospital imaging services.
      PARTICIPANTS: CT scanning patients residing in Otago region during the study
      period. INTERVENTIONS: There is no intervention in this observational study. MAIN
      OUTCOME MEASURES: CT scanning rates and waiting times before and after the
      introduction of the rural scanner. RESULTS: Prior to the scanner being
      commissioned, there was a significant urban versus rural disparity in CT
      utilisation. Residents in the neighbouring urban centre were 1.4 times more
      likely to access CT (33.2 (95% confidence interval (CI) 32.2-34.2) versus 23.0
      (95% CI 21.0-25.1) scans per 1000 residents per annum). Twenty months after the
      scanner was commissioned, the rate for the rural community had almost doubled to
      45.6 (95% CI 43.0-48.2) and was 1.2 times greater than for the urban community.
      This difference was not sustained, and rural and urban communities had similar CT
      scanning rates in 2011 and 2012. Mean waiting time for residents in the rural
      community fell from 21.1 (95% CI 17.1-25.2) days prior to the scanner to 6.7 (95%
      CI 5.6-7.8) days after the scanner was commissioned. CONCLUSIONS: On-site CT
      increased the rural scanning rate, corrected the rural-urban disparity and
      reduced waiting times without apparent over servicing.

PMID- 25594351
TI  - A database survey of equine tumours in the United Kingdom.
AB  - REASONS FOR PERFORMING STUDY: Survey data on equine tumours are sparse compared
      with other species and may have changed over time. OBJECTIVES: To describe the
      most frequently diagnosed equine tumours recorded by a diagnostic pathology
      laboratory over 29 years, to identify background factors associated with tumour
      type, and to identify any changes in the tumours diagnosed or the background of
      cases submitted during the study period. STUDY DESIGN: Observational; cross
      sectional analysis of records of a diagnostic pathology laboratory. METHODS: The
      records of all neoplastic equine histology submissions to the University of
      Bristol (January 1982-December 2010) were accessed from a database, and a list of
      diagnoses compiled. The 6 most commonly diagnosed tumour types were analysed
      using logistic regression to identify background factors associated with tumour
      type. The overall population of equine tumour submissions and the relative
      frequency of diagnosis of the most common tumour types were compared between
      decades. RESULTS: There were 964 cases included. The most frequently diagnosed
      tumours were: sarcoid (24% cases), squamous cell carcinoma (SCC) (19%), lymphoma
      (14%), melanoma (6%), gonadal stromal tumour (6%) and mast cell tumour (MCT)
      (4%). With sarcoid, Thoroughbred/Thoroughbred cross and gelding as reference
      categories: increasing age was significantly associated with the odds of each of
      the other tumour types, mares were at reduced risk of SCC, Arab/Arab cross had a
      higher risk of MCT, Cob/Cob cross had an increased risk of SCC and MCT, and
      ponies had an increased risk of melanoma. The mean age of submissions increased
      in each successive decade and the breed composition became broader. Sarcoids and
      lymphoma formed a smaller proportion of diagnoses in later decades. CONCLUSIONS:
      The types of tumours submitted to this laboratory have changed over the last 3
      decades. Current data inform clinicians and researchers and further studies are
      warranted to follow trends.

PMID- 25594353
TI  - Detection of equine herpesvirus in horses with idiopathic keratoconjunctivitis
      and comparison of three sampling techniques.
AB  - OBJECTIVES: To determine the role of equine herpesvirus (EHV) in idiopathic
      keratoconjunctivitis in horses and to determine whether sample collection method
      affects detection of EHV DNA by quantitative polymerase chain reaction (qPCR).
      ANIMALS STUDIED: Twelve horses with idiopathic keratoconjunctivitis and six
      horses without signs of ophthalmic disease. PROCEDURES: Conjunctival swabs,
      corneal scrapings, and conjunctival biopsies were collected from 18 horses: 12
      clinical cases with idiopathic keratoconjunctivitis and six euthanized controls.
      In horses with both eyes involved, the samples were taken from the eye judged to
      be more severely affected. Samples were tested with qPCR for EHV-1, EHV-2, EHV-4,
      and EHV-5 DNA. Quantity of EHV DNA and viral replicative activity were compared
      between the two populations and among the different sampling techniques; relative
      sensitivities of the sampling techniques were determined. RESULTS: Prevalence of
      EHV DNA as assessed by qPCR did not differ significantly between control horses
      and those with idiopathic keratoconjunctivitis. Sampling by conjunctival swab was
      more likely to yield viral DNA as assessed by qPCR than was conjunctival biopsy.
      EHV-1 and EHV-4 DNA were not detected in either normal or IKC-affected horses;
      EHV-2 DNA was detected in two of 12 affected horses but not in normal horses. EHV
      5 DNA was commonly found in ophthalmically normal horses and horses with
      idiopathic keratoconjunctivitis. CONCLUSIONS: Because EHV-5 DNA was commonly
      found in control horses and in horses with idiopathic keratoconjunctivitis, qPCR
      was not useful for the etiological diagnosis of equine keratoconjunctivitis.
      Conjunctival swabs were significantly better at obtaining viral DNA samples than
      conjunctival biopsy in horses in which EHV-5 DNA was found.

PMID- 25594352
TI  - Recombinant human FVIIa for reducing the need for invasive second-line therapies
      in severe refractory postpartum hemorrhage: a multicenter, randomized, open
      controlled trial.
AB  - BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women
      with severe postpartum hemorrhage (PPH) showed encouraging results, but no
      randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four
      women with severe PPH unresponsive to uterotonics were randomized to receive one
      early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42).
      The primary efficacy outcome measure was the reduction of the need for specific
      second-line therapies, such as interventional hemostatic procedures, for blood
      loss and transfusions. The primary safety outcome measure was the number of
      deaths and thrombotic events during the 5 days following rhuFVIIa infusion.
      RESULTS: rhuFVIIa was associated with a reduction in the number of patients who
      needed second-line therapies compared with controls (standard care).
      Specifically, 39/42 (93%) patients in the standard care arm received second-line
      therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%;
      range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or
      Cesarean section) did not affect the primary outcome. No death occurred. Two
      venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein
      thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism.
      CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics
      shows that rhuFVIIa reduces the need for specific second-line therapies in about
      one in three patients, with the occurrence of non-fatal venous thrombotic events
      in one in 20 patients.

PMID- 25594354
TI  - Living donor liver transplantation using a graft with periportal fibrosis.
AB  - A 57-year-old woman with familial amyloid polyneuropathy (FAP) was scheduled to
      undergo living donor liver transplantation (LDLT), but the operation was
      cancelled because the only potential donor had chronic alcohol-related liver
      disease. One year later, FAP-related neurological symptoms progressed rapidly,
      and emergency LDLT was planned. The donor's hepatic function had returned to
      normal range after 1 year of abstinence. The left liver graft volume was
      equivalent to 37.7% of the standard liver volume (SLV) of the recipient. However,
      a liver biopsy revealed mild fibrosis (score, F1). LDLT was successfully
      performed without any complications. The recipient's neurological findings
      returned to normal. One year after LDLT, the liver graft volume was equivalent to
      approximately 90% of the SLV, and the fibrosis had improved. LDLT using a graft
      with a fibrosis score of up to F1 may be an acceptable alternative for recipients
      with normal hepatic function. 

PMID- 25594355
TI  - Effect of vehicle on the performance of active moisturizing substances.
AB  - PURPOSE: The work is aimed at the description and study of the hydration effect
      of different active substances (hyaluronic acid, sericin, glycerol, and urea)
      incorporated in two different vehicles commonly used for compounding
      pharmaceutical ingredients, gel, and emulsion. METHODS: The effects of the
      formulations were investigated by instrumental methods in vivo after their
      administration to the skin of volar forearms in a group of 20 healthy volunteers
      (women, mean age of 28 years). Hydration effect was observed by corneometry and
      barrier properties (TEWL) by tewametr at regular time intervals (1-26 h) after
      application of the prepared samples. RESULTS: The results indicate that the
      active substances incorporated in the emulsion moisturize the skin better
      compared to the same substances contained in the gel. Furthermore, it was found
      that these ingredients, whether they are present in the emulsion or in the gel,
      prevent TEWL in a similar manner. CONCLUSION: The study showed that differences
      exist among the tested active ingredients in their ability to moisturize the
      skin. These differences are dependent not only on the type and concentration of
      the active substance used but also on the type of vehicle in which they are
      applied. It was also found that the active substances influence the viscosity of
      the prepared formulations.

PMID- 25594356
TI  - Fine particulate matter exposure and initial Pseudomonas aeruginosa acquisition
      in cystic fibrosis.
AB  - RATIONALE: Increasing evidence suggests that exposure to ambient air pollution
      contributes to the severity of cystic fibrosis (CF) respiratory disease in school
      age children and adults; however, the effects of air pollution on young children
      with CF are poorly understood. OBJECTIVES: To investigate the association of
      exposure to fine particulate matter less than 2.5 MUm in aerodynamic diameter
      (PM2.5) and initial Pseudomonas aeruginosa acquisition in young children with CF.
      METHODS: Retrospective analysis of initial Pseudomonas acquisition in children 6
      years of age or younger, using Cystic Fibrosis Foundation National Patient
      Registry data from 2003 to 2009. PM2.5 exposure was estimated by inverse distance
      weighting methods based on air pollution monitors within 30 miles of place of
      residence, for the year before the patient's birth. Multivariable Weibull
      regression with interval-censored outcomes was done to evaluate the association
      of time to initial Pseudomonas acquisition and PM2.5 concentrations. MEASUREMENTS
      AND MAIN RESULTS: A total of 3,575 children met inclusion criteria and 48%
      (n=1,711) acquired Pseudomonas at a median age of 15 months (25th-75th
      percentiles, 9-25 mo). An increase in PM2.5 exposure of 10 MUg/m3 was associated
      with a 24% increased risk of Pseudomonas acquisition (95% confidence interval, 1
      51%) during follow-up. Results were generally consistent across exposure metrics.
      CONCLUSIONS: These results suggest that increased PM2.5 exposure is associated
      with earlier Pseudomonas acquisition in young children with CF and may play an
      important, previously unrecognized, role in the etiology of initial Pseudomonas
      infection.

PMID- 25594358
TI  - Determining high-quality critical body residues for multiple species and
      chemicals by applying improved experimental design and data interpretation
      concepts.
AB  - Ecotoxicological effect data are generally expressed as effective concentrations
      in the external exposure medium and do thus not account for differences in
      chemical uptake, bioavailability, and metabolism, which can introduce substantial
      data variation. The Critical Body Residue (CBR) concept provides clear
      advantages, because it links effects directly to the internal exposure. Using
      CBRs instead of external concentrations should therefore reduce variability. For
      compounds that act via narcosis even a constant CBR has been proposed. Despite
      the expected uniformity, CBR values for these compounds still show large
      variability, possibly due to biased and inconsistent experimental testing. In the
      present study we tested whether variation in CBR data can be substantially
      reduced when using an improved experimental design and avoiding confounding
      factors. The aim was to develop and apply a well-defined test protocol for
      accurately and precisely measuring CBR data, involving improved (passive) dosing,
      sampling, and processing of organisms. The chemicals 1,2,4-trichlorobenzene,
      1,2,3,4-tetrachlorobenzene, 2,3,4-trichloroaniline, 2,3,5,6-tetrachloroaniline, 4
      chloro-3-methylphenol, pentylbenzene, pyrene, and bromophos-methyl were tested on
      Lumbriculus variegatus (California blackworm), Hyalella azteca (scud), and
      Poecilia reticulata (guppy), which yielded a high-quality database of 348
      individual CBR values. Medians of CBR values ranged from 2.1 to 16.1 mmol/kg wet
      weight (ww) within all combinations of chemicals and species, except for the
      insecticide bromophos-methyl, for which the median was 1.3 mmol/kg ww. The new
      database thus covers about one log unit, which is considerably less than in
      existing databases. Medians differed maximally by a factor of 8.4 between the 7
      chemicals but within one species, and by a factor of 2.6 between the three
      species but for individual chemicals. Accounting for the chemicals' internal
      distribution to different partitioning domains and relating effects to estimated
      concentrations in the target compartment (i.e., membrane lipids) was expected to
      but did not decrease the overall variability, likely because the surrogate
      partition coefficients for membrane lipid, storage lipid, protein, and
      carbohydrate that were used as input parameters did not sufficiently represent
      the actual partitioning processes. The results of this study demonstrate that a
      well-designed test setup can produce CBR data that are highly uniform beyond
      chemical and biological diversity.

PMID- 25594357
TI  - VIDA: a voxel-based dosimetry method for targeted radionuclide therapy using
      Geant4.
AB  - We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to
      provide patient-specific dosimetry in targeted radionuclide therapy performing
      Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code
      generates voxel-level dose rate maps using anatomical and physiological data
      taken from individual patients. Voxel level dose rate curves are then fit and
      integrated to yield a spatial map of radiation absorbed dose. In this article, we
      present validation studies using established dosimetry results, including self
      dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit
      density spheres and organ self- and cross-organ DFs in the Radiation Dose
      Assessment Resource (RADAR) reference adult phantom. The comparison with
      reference data demonstrated agreement within 5% for self-DFs to spheres and
      reference phantom source organs for four common radionuclides used in targeted
      therapy ((131)I, (90)Y, (111)In, (177)Lu). Agreement within 9% was achieved for
      cross-organ DFs. We also present dose estimates to normal tissues and tumors from
      studies of two non-Hodgkin Lymphoma patients treated by (131)I
      radioimmunotherapy, with comparison to results generated independently with
      another dosimetry code. A relative difference of 12% or less was found between
      methods for mean absorbed tumor doses accounting for tumor regression. 

PMID- 25594359
TI  - Midtarsal break variation in modern humans: Functional causes, skeletal
      correlates, and paleontological implications.
AB  - The midtarsal break was once treated as a dichotomous, non-overlapping trait
      present in the foot of non-human primates and absent in humans. Recent work
      indicates that there is considerable variation in human midfoot dorsiflexion,
      with some overlap with the ape foot. These findings have called into question the
      uniqueness of the human lateral midfoot, and the use of osteological features in
      fossil hominins to characterize the midfoot of our extinct ancestors. Here, we
      present data on plantar pressure and pedal mechanics in a large sample of adults
      and children (n = 671) to test functional hypotheses concerning variation in
      midfoot flexibility. Lateral midfoot peak plantar pressure correlates with both
      sagittal plane flexion at the lateral tarsometatarsal joint, and dorsiflexion at
      the hallucal metatarsophalangeal joint. The latter finding suggests that midfoot
      laxity may compromise hallucal propulsion. Multiple regression statistics
      indicate that a low arch and pronation of the foot explain 40% of variation in
      midfoot peak plantar pressure, independent of age and BMI. MRI scans on a small
      subset of study participants (n = 19) reveals that curvature of the base of the
      4th metatarsal correlates with lateral midfoot plantar pressure and that specific
      anatomies of foot bones do indeed reflect relative midfoot flexibility. However,
      while the shape of the base of the 4th metatarsal may reliably reflect midfoot
      mobility in individual hominins, given the wide range of overlapping variation in
      midfoot flexibility in both apes and humans, we caution against generalizing foot
      function in extinct hominin species until larger fossils samples are available.

PMID- 25594362
TI  - Tetrahydropyran- and tetrahydrofuran-containing diarylheptanoids from Hedychium
      coronarium rhizomes.
AB  - Seven new diarylheptanoids (1-7) were isolated from the n-BuOH-soluble fraction
      of the rhizome of Hedychium coronarium. Hedycoropyrans A-C (1-3) contain a
      tetrahydropyran moiety, while hedycorofurans A-D (4-7) contain a tetrahydrofuran
      moiety, belonging to a rare structural class of diarylheptanoids. Their
      structures including stereochemistry were elucidated on the basis of 1D and 2D
      NMR and ECD spectroscopic analyses and HRESIMS data of the parent compounds and
      the isopropylidene derivatives of 4 and 7. 

PMID- 25594361
TI  - A mild one-pot process for synthesising hydroxyapatite/biomolecule bone scaffolds
      for sustained and controlled antibiotic release.
AB  - The release of active molecules or the control of nosocomial infections for
      improved osteoinduction is ideally addressed by a bone substitute material. For
      this purpose, the feasibility of a mild one-pot process is probed for
      incorporating directly active proteins and antibiotics in a hydroxyapatite (HAp)
      based scaffold. The effect of two serum model proteins, bovine serum albumin
      (BSA) and fibrinogen (FIB), on the microstructure, on selected mechanical
      properties as well as on degradation behaviour and on protein release are
      investigated. By protein incorporation, the porosity can be adjusted between 54
      and 70% especially due to the foaming ability of BSA. The addition of 5 wt% FIB
      doubles the biaxial flexural strength up to 6 MPa in comparison to samples
      without proteins (3 MPa). Protein release experiments show that a rapid release
      takes place within the first days (between around 3% for FIB and 38% for BSA). As
      a possible application for osteomyelitis treatment, vancomycin and gentamicin
      were subsequently added instead of proteins to study their release behaviour and
      their antibacterial activity, respectively. A controlled antibiotic release was
      observed for a period of 18 d. By varying the protein type, mixture and quantity,
      the mechanical strength porosity as well as the protein release and calcium
      solubility can be controlled. Our studies underpin the suitability of this mild
      one-pot process as a promising simple-to-use platform for controlled local drug
      release and bone treatment. 

PMID- 25594360
TI  - The impact of a telenovela intervention on use of home health care services and
      Mexican American older adult and caregiver outcomes.
AB  - A two-group randomized controlled trial tested a telenovela intervention (i.e., a
      culturally congruent videotaped dramatization with guided dialogue) to increase
      Mexican American older adults' and family caregivers' awareness of and confidence
      in home health care services (HHCS), thereby increasing use of HHCS and improving
      older adult and caregiver outcomes. Both groups had significant increases in
      awareness of and confidence in HHCS. The intervention group used HHCS more than
      the control group (91.1% versus 71.2% of total visits authorized); however, this
      was not a statistically significant difference (p = 0.18). Use of HHCS was
      associated with increased older adult and caregiver mutuality (i.e., the quality
      of the older adult-caregiver relationship) and decreased caregiving burden and
      depression. The predictive role and measurement of awareness and ways to improve
      the intervention are discussed. Findings are especially important with today's
      focus on transitional care to keep older adults at home and prevent unnecessary
      readmissions.

PMID- 25594363
TI  - Segregation of In to dislocations in InGaN.
AB  - Dislocations are one-dimensional topological defects that occur frequently in
      functional thin film materials and that are known to degrade the performance of
      InxGa1-xN-based optoelectronic devices. Here, we show that large local deviations
      in alloy composition and atomic structure are expected to occur in and around
      dislocation cores in InxGa(1-x)N alloy thin films. We present energy-dispersive X
      ray spectroscopy data supporting this result. The methods presented here are also
      widely applicable for predicting composition fluctuations associated with strain
      fields in other inorganic functional material thin films.

PMID- 25594364
TI  - Texercise Effectiveness: Impacts on Physical Functioning and Quality of Life.
AB  - This study examines the effectiveness of Texercise Select, a 12-week lifestyle
      program to improve physical functioning (as measured by gait speed) and quality
      of life. Baseline and 12-week follow-up assessments were collected from 220
      enrollees who were older (mean = 75 years), predominantly female (85%), White
      (82%), and experiencing multiple comorbidities (mean = 2.4). Linear mixed-models
      were fitted for continuous outcome variables and GEE models with logit link
      function for binary outcome variables. At baseline, over 52% of participants had
      Timed Up-and-Go (TUG) test times of 12 s or more, which indicates below-normal
      performance. On average, participants showed significant reductions in TUG test
      scores at the postintervention (11% reduction, p < .001). Participants also
      showed significant improvements in general health status (p = .002), unhealthy
      physical days (p = .032), combined unhealthy physical and mental days (p = .006),
      and days limited from usual activity (p = .045). Findings suggest that
      performance indicators can be objectively collected and integrated into
      evaluation designs of community-based, activity-rich lifestyle programs. 

PMID- 25594365
TI  - Facilitated ion diffusion in multiscale porous particles: application in battery
      separators.
AB  - Polyethylene (PE) separators have been the most popular option for commercial Li
      ion batteries because of their uniform pore size, high tensile strength, low
      cost, and electrochemical stability. Unfortunately, PE separators generally
      suffer from significant dimensional changes at high temperatures, which
      frequently results in serious safety problems. In this regard, the integration of
      inorganic nanoparticles with PE separators has been considered to be a promising
      approach. Here, inorganic nanoparticles with a hierarchical pore structure were
      coated on a conventional polymer separator. The resultant composite separator
      exhibited superior Li ion transportation compared with separators coated with
      mesopore-only nanoparticles or conventional nonporous nanoparticles. The
      mesopores and macropores act synergistically to improve the electrolyte uptake
      and ionic conductivity of the inorganic nanoparticles, while other positive
      aspects such as their thermal and mechanical properties are still maintained. 

PMID- 25594367
TI  - Effect of acidity upon attrition-corrosion of human dental enamel.
AB  - Attrition-corrosion is a synthesized human enamel wear process combined
      mechanical effects (attrition) with corrosion. With the rising consumption of
      acidic food and beverages, attrition-corrosion is becoming increasingly common.
      Yet, research is limited and the underlying mechanism remains unclear. In this
      study, in vitro wear loss of human enamel was investigated and the attrition
      corrosion process and wear mechanism were elucidated by the analysis of the wear
      scar and its subsurface using focused ion beam (FIB) sectioning and scanning
      electron microscopy (SEM). Human enamel flat-surface samples were prepared with
      enamel cusps as the wear antagonists. Reciprocating wear testing was undertaken
      under load of 5N at the speed of 66 cycle/min for 2250 cycles with lubricants
      including citric acid (at pH 3.2 and 5.5), acetic acid (at pH 3.2 and 5.5) and
      distilled water. All lubricants were used at 37 degrees C. Similar human enamel
      flat-surface samples were also exposed to the same solutions as a control group.
      The substance loss of enamel during wear can be linked to the corrosion potential
      of a lubricant used. Using a lubricant with very low corrosion potential (such as
      distilled water), the wear mechanism was dominated by delamination with high wear
      loss. Conversely, the wear mechanism changed to shaving of the softened layer
      with less material loss in an environment with medium corrosion potential such as
      citric acid at pH 3.2 and 5.5 and acetic acid at pH 5.5. However, a highly
      corrosive environment (e.g., acetic acid at pH 3.2) caused the greatest loss of
      substance during wear. 

PMID- 25594366
TI  - Potential proinflammatory and osteogenic effects of dicalcium silicate particles
      in vitro.
AB  - BACKGROUND: Due to their biocompatibility and bioactivity, dicalcium silicate
      (C2S) and hydroxyapatite (HA) are used as coating materials for prosthetic
      orthopedic and dental implants or as bone substitute materials to fill bone
      defects. However, prostheses and bone substitutes can release particles that
      trigger an immune response in the recipient. The immunological effects of C2S
      particles have not yet been studied. OBJECTIVE: The aim of this study was to
      determine the cytotoxic effects of C2S particles on primary human monocytes, a
      human monocyte cell line (THP-1) and an osteoblast-like cell line (MG-63). The
      proinflammatory effects of C2S particles on THP-1 were also detected. Moreover,
      the osteogenic effects of C2S and HA on MG-63 cells were investigated. METHODS:
      Characterization of C2S and HA was performed using scanning electron microscopy
      (SEM), energy dispersive analysis (EDS), X-ray diffraction (XRD), Brunner-Emmett
      Teller (BET) measurements and laser diffraction. The cytotoxic effect of C2S on
      primary human monocytes as well as THP-1 and MG-63 cells was measured using
      Trypan blue assays, Cell Counting Kit-8 (CCK-8) assays and flow cytometry to
      detect apoptosis. THP-1 human monocytes with or without lipopolysaccharide (LPS)
      stimulation were exposed to C2S and HA for 6 and 24h. Thereafter, the mRNA
      expression and protein concentrations of MMP-2, MMP-9, TIMP-2, TIMP-1 and TNF
      alpha were evaluated using real-time PCR and ELISA, respectively. RANKL and OPG
      mRNA expression levels in MG-63 cells were examined using real-time PCR. RESULTS:
      No significant cytotoxicity was recorded when cells were directly cultured with
      C2S/HA particles. After THP-1 cells were cultured with C2S/HA for 24h, MMP-2, MMP
      9 and TNF-alpha expression increased, whereas TIMP-2 and TIMP-1 expression
      decreased. Compared with HA, C2S slightly increased MMP-9 expression and slightly
      decreased TIMP-1 expression. The MMP: TIMP ratio increased in the C2S and HA
      groups; however, HA significantly increased the MMP-9: TIMP-1 ratio compared with
      C2S. Compared with HA, C2S caused less TNF-alpha production. C2S/HA did not
      modify the expression of proinflammatory mediators in LPS-stimulated cells.
      Furthermore, C2S/HA significantly increased OPG expression and slightly increased
      RANKL expression in MG-63 cells. C2S and HA decreased the RANKL: OPG ratio.
      CONCLUSION: Our in vitro data suggest that C2S is relatively safe when directly
      cultured with cells. In addition, C2S may exert proinflammatory effects; however,
      compared with HA, C2S had fewer proinflammatory effects on THP-1. C2S and HA did
      not alter the LPS-induced production of proinflammatory mediators and had similar
      osteogenic effects on MG-63 cells.

PMID- 25594368
TI  - CO2 capture and separation from N2/CH4 mixtures by Co@B8/Co@B8(-) and M@B9/M@B9(
      ) (M = Ir, Rh, Ru) clusters: a theoretical study.
AB  - The discovery of advanced materials with high selectivity and efficiency is
      essential to realize practical carbon capture and sequestration. Here, we have
      investigated the interactions of the Co@B8/Co@B8(-) and M@B9/M@B9(-) (M = Ir, Rh,
      Ru) clusters with CO2, N2, and CH4 gas molecules theoretically. We found that
      neutral boron clusters have weak interaction with CO2, N2, and CH4 molecules.
      Similarly, the clusters with their negative charge states have also weak
      interaction with N2 and CH4 molecules. However, anionic clusters have a strong
      interaction with CO2, which can be explained by the Lewis acid-base interaction
      as CO2 (Lewis acid) can gain electron easily from the electron-rich anionic
      clusters. Moreover, the kinetic stability of the formed complexes after CO2
      capture has been validated by ab initio molecular dynamics. In all, the present
      study demonstrates, for the first time, that the anionic boron wheel ring
      clusters can be used as potential advanced materials for CO2 capture and
      separation from flue gas and natural gas mixtures. 

PMID- 25594369
TI  - Immobilization of polyoxometalates in the Zr-based metal organic framework UiO
      67.
AB  - The encapsulation of polyoxometalates within the large pores of the Zr(iv)
      biphenyldicarboxylate UiO-67 metal-organic framework has been achieved, for the
      first time, by direct solvothermal synthesis. The resulting POM@UiO-67 composite
      materials were fully characterized by XRPD, IR, MAS NMR, N2 porosimetry
      measurements and cyclic voltammetry. 

PMID- 25594370
TI  - Prolonged Exposure for PTSD in a Veteran group: a pilot effectiveness study.
AB  - Previous research has consistently demonstrated that Prolonged Exposure (PE)
      therapy is an effective treatment for posttraumatic stress disorder (PTSD).
      Traditionally, PE has been studied and delivered on an individual basis. However,
      the growing number of Veterans in need of PTSD treatment has led to increased
      interest in group therapies as an efficient way to provide access to care. The
      current study examined a group and individual hybrid treatment that was developed
      based on PE principles. Treatment was 12 weeks in length and consisted of 12 one
      hour group sessions focused on in vivo exposures, and an average of approximately
      five-hour long individual imaginal exposure sessions. Data for this study were
      derived from 67 veterans who participated in 12 cohorts of the Group PE.
      Significant reductions in PTSD and depression symptoms were found in both
      completers and intent-to-treat sample analyses. The clinical implications of
      these findings are discussed. 

PMID- 25594372
TI  - Nutrient levels modify saltmarsh responses to increased inundation in different
      soil types.
AB  - Saltmarshes have been depleted historically, and cumulative stressors threaten
      their future persistence. We examined experimentally how nutrient availability
      (high vs. low) affects the responses of Spartina maritima to increased inundation
      in two mineral soil types (low vs. medium organic). Increased inundation, one of
      the effects of accelerated sea level rise, had negative effects on most plant
      growth parameters, but the magnitude varied with soil and nutrient levels, and
      between plants from different locations. Average differences between inundation
      treatments were largest at high nutrient conditions in low organic matter soils.
      We conclude that saltmarsh vegetation would be more drastically affected by
      increased inundation in low than in medium organic matter soils, and especially
      in estuaries already under high nutrient availability. This knowledge enhances
      the prediction of changes at the foreshore of saltmarshes related to sea level
      rise, and the development of site-specific conservation strategies. 

PMID- 25594373
TI  - Assessment of apical periodontitis by MRI: a feasibility study.
AB  - PURPOSE: The purpose of this clinical feasibility study was to evaluate the
      applicability of magnetic resonance imaging (MRI) for the assessment of apical
      periodontitis in direct comparison with cone beam CT (CBCT). MATERIALS AND
      METHODS: 19 consecutive patients (average age 43 +/- 13 years) with 34 lesions in
      total (13 molars, 14 premolars and 7 front teeth) were enrolled in this
      feasibility study. Periapical lesions were defined as periapical radiolucencies
      (CBCT) or structural changes in the spongy bone signal (MRI), which were
      connected with the apical part of a root and with at least twice the width of the
      periodontal ligament space. The location and dimension of the lesions were
      compared between MRI and CBCT. RESULTS: While mainly mineralized tissue
      components such as teeth and bone were visible with CBCT, complimentary
      information of the soft tissue components was assessable with MRI. The MRI images
      provided sufficient diagnostic detail for the assessment of the main structures
      of interest. Heterogeneous contrast was observed within the lesion, with often a
      clear enhancement close to the apical foramen and the periodontal gap.  No
      difference for lesion visibility was observed between MRI and CBCT. The lesion
      dimensions corresponded well, but were slightly but significantly overestimated
      with MRI. A heterogeneous lesion appearance was observed in several patients.
      Four patients presented with a well circumscribed hyperintense signal in the
      vicinity of the apical foramen. CONCLUSION: The MRI capability of soft tissue
      characterization may facilitate detailed analysis of periapical lesions. This
      clinical study confirms the applicability of multi-contrast MRI for the
      identification of periapical lesions. KEY POINTS: MRI can be applied for the
      identification of periapical lesions without ionizing radiation exposure. MRI
      might facilitate more detailed characterization of periapical lesions. MRI might
      provide more accurate lesion dimensions as X-ray-based methods.

PMID- 25594374
TI  - Diagnostic accuracy of elastography and scintigraphic imaging after thermal
      microwave ablation of thyroid nodules.
AB  - PURPOSE: The aim of this study is to evaluate structural alterations of thyroid
      tissue after microwave ablation using elastography and scintigraphic imaging to
      investigate the applicability of these diagnostic methods for follow-up. 
      MATERIALS AND METHODS: 35 patients with 39 thyroid nodules were evaluated using
      elastography and scintigraphic imaging before and after ultrasound-guided
      microwave ablation. Elastography was analyzed according to color-coded output and
      results were classified using a fourfold elasticity score (ES). Nodules color
      coded blue were classified ES1 for high elasticity through ES2 and ES3 for lower
      elasticity, and nodules with very low elasticity were color-coded red and
      classified as ES4. (99m)Tc-pertechnetate served as a tracer for scintigraphic
      imaging of hot and indifferent nodules and (99m)Tc-MIBI for cold nodules.
      RESULTS: Before microwave ablation, elastography detected a median elasticity
      score of ES 2 +/- 0.7, and after ablation the median score was ES 3 +/- 0.6.
      Overall, the median score increased by 1ES +/- 0.6 (p < 0.01). Scintigraphic
      imaging detected a median reduction of tracer uptake in ablated tissue of 38.7
      %+/- 27.5(p < 0.01). (99m)Tc-pertechnetate scans showed a median decrease of
      tracer uptake of 26.3 %+/- 16.3 and (99m)Tc-MIBI scans detected uptake reduction
      of 54.7 %+/- 29.2. CONCLUSION: Scintigraphic imaging using (99m)Tc-pertechnetate
      and (99m)Tc-MIBI provides quantifiable results and is promising as a diagnostic
      follow-up after microwave ablation. Strain elastography detects decreasing tissue
      elasticity, but accuracy is limited by the necessary reduction of color-coded
      output to elasticity scores.

PMID- 25594371
TI  - An alpha-synuclein gene (SNCA) polymorphism moderates the association of PTSD
      symptomatology with hazardous alcohol use, but not with aggression-related
      measures.
AB  - Posttraumatic stress disorder (PTSD) often precedes comorbid substance use
      disorder and has been associated with aggression. Prior research has evidenced
      that alcohol use and other externalizing behaviors share genetic factors with
      PTSD; however, few studies have examined if specific genes are associated with
      externalizing behaviors in PTSD. The purpose of the current study was to
      investigate whether an alpha-synuclein gene polymorphism (SNCA rs356195)
      moderates the association of PTSD symptomatology with externalizing behaviors. We
      examined the separate and combined effects of PTSD symptomatology and SNCA
      rs356195 on alcohol- and aggression-related measures in nonclinical participants
      (N=138 European Americans; 15 diagnosed with probable PTSD). Probable PTSD status
      and SNCA were both associated with externalizing measures. SNCA also moderated
      the association of PTSD symptomatology with hazardous alcohol use, but not with
      aggression-related measures. Current findings suggest that variations in SNCA may
      increase the likelihood that PTSD symptomatology results in excessive alcohol
      use. 

PMID- 25594375
TI  - The discrepancy between the absence of copper deposition and the presence of
      neuronal damage in the brain of Atp7b(-/-) mice.
AB  - Wilson's disease (WD) is caused by mutations within the copper-transporting
      ATPase (ATP7B), characterized by copper deposition in various organs, principally
      the liver and the brain. With the availability of Atp7b(-/-) mice, the valid
      animal model of WD, the mechanism underlying copper-induced hepatocyte necrosis
      has been well understood. Nonetheless, little is known about the adverse impact
      of copper accumulation on the brain in WD. Therefore, the aim of this study was
      to identify copper disturbances according to various brain compartments and
      further dissect the causal relationship between copper storage and neuronal
      damage using Atp7b(-/-) mice. Copper levels in the liver, whole brain, brain
      compartments and basal ganglia mitochondria of Atp7b(-/-) mice and age-matched
      controls were measured by atomic absorption spectroscopy. Delicate electron
      microscopic studies on hepatocytes and neurons in the basal ganglia were
      performed. Here we further confirmed the remarkably elevated copper content and
      abnormal ultrastructure findings in livers of Atp7b(-/-) mice. Interestingly, we
      found the ultrastructure abnormalities in neurons of the basal ganglia of Atp7b(
      /-) mice, whereas copper deposition was not detected in the whole brain, even
      within the basal ganglia and its mitochondria. The disparity provided a new
      understanding of neuronal dysfunction in WD, and strongly indicated that copper
      might not be the sole causative player and other unidentified pathogenic factors
      could enhance the toxic effects of copper on neurons in WD. 

PMID- 25594377
TI  - The impact of concurrent visual feedback on coding of on-line and pre-planned
      movement sequences.
AB  - The purpose of this study was to determine the extent to which participants could
      effectively switch from on-line (OL) to pre-planned (PP) control (or vice versa)
      depending on previous practice conditions and whether concurrent visual feedback
      was available during transfer testing. The task was to reproduce a 2000 ms
      spatial-temporal pattern of a sequence of elbow flexions and extensions.
      Participants were randomly assigned to one of two practice conditions termed OL
      or PP. In the OL condition the criterion waveform and the cursor were provided
      during movement production while this information was withheld during movement
      production for the PP condition. A retention test and two effector transfer tests
      were administered to half of the participants in each acquisition conditions
      under OL conditions and the other half under PP conditions. The mirror effector
      transfer test required the same pattern of muscle activation and limb joint
      angles as required during acquisition. The non-mirror transfer test required
      movements to the same visual-spatial locations as experienced during acquisition.
      The results indicated that when visual information was available during the
      transfer tests performers could switch from PP to OL. When visual information was
      withdrawn, they shifted from the OL to the PP-control mode. This finding suggests
      that performers adopt a mode of control consistent with the feedback conditions
      provided during testing.

PMID- 25594378
TI  - Electrochemical nanocomposite-derived sensor for the analysis of chemical oxygen
      demand in urban wastewaters.
AB  - This work reports on the fabrication and comparative analytical assessment of
      electrochemical sensors applied to the rapid analysis of chemical oxygen demand
      (COD) in urban waste waters. These devices incorporate a carbon nanotube
      polystyrene composite, containing different inorganic electrocatalysts, namely,
      Ni, NiCu alloy, CoO, and CuO/AgO nanoparticles. The sensor responses were
      initially evaluated using glucose as standard analyte and then by analyzing a set
      of real samples from urban wastewater treatment plants. The estimated COD values
      in the samples were compared with those provided by an accredited laboratory
      using the standard dichromate method. The sensor prepared with the CuO/AgO-based
      nanocomposite showed the best analytical performance. The recorded COD values of
      both the sensor and the standard method were overlapped, considering the 95%
      confidence intervals. In order to show the feasible application of this approach
      for the detection of COD online and in continuous mode, the CuO/AgO-based
      nanocomposite sensor was integrated in a compact flow system and applied to the
      detection of wastewater samples, showing again a good agreement with the values
      provided by the dichromate method. 

PMID- 25594376
TI  - Predictive motor control of sensory dynamics in auditory active sensing.
AB  - Neuronal oscillations present potential physiological substrates for brain
      operations that require temporal prediction. We review this idea in the context
      of auditory perception. Using speech as an exemplar, we illustrate how
      hierarchically organized oscillations can be used to parse and encode complex
      input streams. We then consider the motor system as a major source of rhythms
      (temporal priors) in auditory processing, that act in concert with attention to
      sharpen sensory representations and link them across areas. We discuss the
      circuits that could mediate this audio-motor interaction, notably the potential
      role of the somatosensory system. Finally, we reposition temporal predictions in
      the context of internal models, discussing how they interact with feature-based
      or spatial predictions. We argue that complementary predictions interact
      synergistically according to the organizational principles of each sensory
      system, forming multidimensional filters crucial to perception. 

PMID- 25594379
TI  - Structural analysis of dopamine- and amphetamine-induced depolarization currents
      in the human dopamine transporter.
AB  - Amphetamine (AMPH) induces depolarizing currents through the human dopamine
      transporter (hDAT). Recently we discovered that the S(+) enantiomer of AMPH
      induces a current through hDAT that persists long after its removal from the
      external milieu. The persistent current is less prominent for R(-)AMPH and
      essentially absent for dopamine (DA)-induced currents. Related agents such as
      methamphetamine also exhibit persistent currents, which are present in both frog
      oocyte and mammalian HEK expression systems. Here, we study hDAT-expressing
      Xenopus laevis oocytes voltage-clamped and exposed from outside to DA, S(+)AMPH,
      R(-)AMPH, and related synthesized compounds, including stereoisomers. The goal of
      the study was to determine how structural transitioning from dopamine to
      amphetamine influences hDAT potency and action. At saturating concentrations,
      S(+)AMPH or R(-)AMPH induce a sharply rising depolarizing current from -60 mV
      that is comparable in amplitude to DA-induced currents. The magnitude and
      duration of the currents and the presence or absence of persistent currents
      depend on the concentration, duration of exposure, and chemical structure and
      enantiomeric versions of the agents.

PMID- 25594380
TI  - Tandem amine and ruthenium-catalyzed hydrogenation of CO2 to methanol.
AB  - This Communication describes the hydrogenation of carbon dioxide to methanol via
      tandem catalysis with dimethylamine and a homogeneous ruthenium complex. Unlike
      previous examples with homogeneous catalysts, this CO2-to-CH3OH process proceeds
      under basic reaction conditions. The dimethylamine is proposed to play a dual
      role in this system. It reacts directly with CO2 to produce dimethylammonium
      dimethylcarbamate, and it also intercepts the intermediate formic acid to
      generate dimethylformamide. With the appropriate selection of catalyst and
      reaction conditions, >95% conversion of CO2 was achieved to form a mixture of
      CH3OH and dimethylformamide. 

PMID- 25594382
TI  - Diagnostic performance of multidetector computed tomography in distinguishing
      unilateral from bilateral abnormalities in primary hyperaldosteronism: comparison
      of multidetector computed tomography with adrenal vein sampling.
AB  - OBJECTIVE: The management of patients with primary hyperaldosteronism (PH) varies
      depending on whether the unregulated aldosterone secretion localizes to a single
      unilateral adrenal gland, traditionally determined using adrenal vein sampling
      (AVS). This study seeks to determine if the performance of multidetector computed
      tomography (MDCT) examinations performed using the latest scanner technology can
      reasonably match the results of AVS, and potentially avoid AVS in some patients.
      MATERIALS AND METHODS: Computed tomographic scans in 56 patients with PH were
      independently reviewed by 2 radiologists for the presence of adrenal nodules and
      qualitative adrenal thickening. Results were correlated with AVS results.
      RESULTS: Of 35 patients with MDCT evidence of unilateral nodules, the imaging
      findings correctly predicted AVS localization in only 23 (65.7%) cases. When
      stratified by size, MDCT was accurate in only 71.4% of cases for nodules
      measuring 10 mm or less, and only 55.0% of cases for nodules measuring 11 to 20
      mm. Of the 12 cases where MDCT did not correctly localize, AVS localized to the
      contralateral adrenal gland in 4 cases, whereas AVS suggested no lateralization
      in 8 cases. In patients with normal bilateral adrenal glands on MDCT, 2/7 (28.6%)
      of cases demonstrated unilateral localization on AVS, and in patients with
      bilateral adrenal nodules, only 3/14 (21.4%) did not demonstrate lateralization
      on AVS. CONCLUSIONS: Multidetector computed tomography, even when performed with
      the latest generation of MDCT scanners, does not offer sufficient diagnostic
      accuracy to replace AVS in patients with PH.

PMID- 25594383
TI  - Computed Tomographic Findings of Enterohemorrhagic Escherichia coli O157
      Infection: An Analysis of a 7-Case Regional Outbreak.
AB  - PURPOSE: We experienced an outbreak of enterohemorrhagic Escherichia coli (EHEC)
      colitis. The purpose of this study was to reveal the computed tomographic (CT)
      findings on EHEC colitis. METHODS: The subjects were 7 patients with EHEC
      colitis, which was caused by eating a contaminated Japanese rice cake. Contrast
      CT was performed on all patients. Two radiologists evaluated the CT findings (the
      thickness of colon wall, the range of thickened colon, and the existence of dirty
      fat signs around the colon, ascites, and swelling of lymph nodes), in accordance
      with our PACS system. RESULTS: Wall swelling of the proximal colon from cecum to
      ascending colon was noted in all patients. Small intestine lesions were not noted
      in any cases. CONCLUSIONS: We should consider EHEC infection as part of a
      differential diagnosis when the findings of severe right colitis are seen without
      enteritis.

PMID- 25594385
TI  - Anomalous origin of the left coronary artery from the pulmonary artery in
      infants: imaging findings and clinical implications of cardiac computed
      tomography.
AB  - PURPOSE: This study aimed to retrospectively analyze the imaging features of an
      anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      in pediatric patients, with cardiac computed tomography (CT) and
      echocardiography. MATERIALS AND METHODS: To define the precise location of ostium
      of the left coronary artery, we examined 9 patients using chest film,
      electrocardiogram, echocardiography, and cardiac CT 4 modalities, 2 of them also
      using cardiac MR and 1 of them using catheter cardiac angiography. Cardiac CT
      scan was performed in all 9 patients using a body size adapted low-dose protocol
      after bolus injection of intravenous nonionic contrast medium. Multiplane
      reconstruction, maximum intensity projection, and 3-dimensional coronary tree
      images were obtained for each patient. Two radiologists in consensus analyzed the
      cardiac CT findings for the origin of the anomalous coronary artery, course, and
      collateral vessels. The ALCAPA in these 9 patients was confirmed retrospectively
      by surgery. RESULTS: Cardiac CT can distinguish the site of origin of the
      anomalous left coronary artery and variants: 2 patients with inner ostium of the
      pulmonary trunk, 3 patients with left-sided ostium, 2 patients with posterior
      ostium, and 2 patients with sinus of the pulmonary root ostium; 1 patient
      combined with the right coronary artery arising from the left coronary sinus.
      CONCLUSIONS: Cardiac CT can provide fast and accurate depiction of complex
      coronary arteries, particularly in unstable and fragile patients with ALCAPA, and
      according to cardiac CT, surgical strategies can be decided.

PMID- 25594384
TI  - Tendinopathy of the achilles tendon: volume assessed by automated contour
      detection in submillimeter isotropic 3-dimensional magnetic resonance imaging
      data sets recorded at a field strength of 3 T.
AB  - OBJECTIVE: This prospective study assesses volume changes of the Achilles tendon
      in case of chronic tendinopathy (TEN), using an automated contour detection
      algorithm in submillimeter isotropic 3-dimensional magnetic resonance imaging
      data sets, recorded at 3 T. METHODS: Forty-one subjects (median age, 40 years;
      range, 19-68 years) were included in this prospective study and underwent
      nonenhanced magnetic resonance imaging of both Achilles tendons at 3 T, deploying
      a T2-weighted 3-dimensional Fast-Spin-Echo sequence with submillimeter resolution
      of 0.8 mm. Of the 41 subjects, 13 were classified as patients with TEN and 28
      were healthy volunteers and served as control group. Of the 13 patients, 10 had
      unilateral TEN and 3 had bilateral TEN. Achilles tendons were automatically
      segmented in the T2-weighted magnetic resonance data sets for the evaluation of
      the tendon volume (0-3 cm proximal to the cranial border of the calcaneal bone).
      The total volume (length, 3 cm) was divided in 3 subvolumes of 1 cm length, named
      volume (0-1 cm), volume (1-2 cm), and volume (2-3 cm). Minimum and maximum tendon
      cross-sectional area within the total volume was processed. A standardized pain
      questionnaire was obtained from all patients. RESULTS: The automated contour
      detection algorithm worked reliably in all cases. The TEN group showed a
      significantly increased tendon volume compared to the control group (mean volume,
      2.94 vs 2.43 mm; P < 0.05). The difference was most obvious concerning volume (2
      3 cm) (P < 0.0001). Evaluation of clinical severity revealed a moderate
      correlation between VISA-score and tendon volume (2-3 cm) as well as the
      maximum/minimum tendon area (rho = -0.44, rho = -0.48, and rho = -0.41). In case
      of unilateral TEN, the symptomatic side showed an increased tendon volume (2-3
      cm) and increased minimum area (P < 0.05). CONCLUSIONS: Tendon volume and size
      are adequate surrogate parameters to differentiate patients with chronic TEN from
      healthy subjects, and may discriminate symptomatic TEN from asymptomatic "silent"
      TEN in patients with unilateral symptoms.

PMID- 25594386
TI  - Retrofacial approach to access the round window for cochlear implantation of
      malformed ears.
AB  - OBJECTIVE: To report the use of the retrofacial approach for cochlear
      implantation in three cases of malformed ears with inaccessible round windows
      through the standard facial recess. PATIENTS: Two children with bilateral
      profound sensorineural hearing loss who were cochlear implant candidates. One
      patient had bilateral sequential cochlear implantations and the other a
      unilateral implant. INTERVENTION(S): Retrofacial approach to access the posterior
      mesotympanum and visualize the round window. MAIN OUTCOME MEASURE(S): Ability to
      complete the surgery with full insertion of the implant and no complications such
      as facial nerve injury. RESULTS: We implanted three ears in two patients with
      multiple external and middle ear malformations with an aberrant facial nerve or a
      posteriorly displaced round window niche. The standard facial recess approach did
      not allow visualization of the round window. We resorted to a retrofacial
      approach to access the posterior mesotympanum and proceeded with the surgery
      through an anterior and inferior cochleostomy or through the round window.
      CONCLUSION: In cases with an aberrant facial nerve or inaccessible round window
      through the facial recess, the retrofacial approach is a good alternative but
      requires a certain level of expertise and familiarity with temporal bone anatomy.
      The decision to use an unconventional approach should be considered before
      surgery, but the ultimate decision may require intraoperative assessment.

PMID- 25594387
TI  - The impact of cochlear implantation on speech understanding, subjective hearing
      performance, and tinnitus perception in patients with unilateral severe to
      profound hearing loss.
AB  - OBJECTIVES: This study aimed to determine the impact of cochlear implantation on
      speech understanding in noise, subjective perception of hearing, and tinnitus
      perception of adult patients with unilateral severe to profound hearing loss and
      to investigate whether duration of deafness and age at implantation would
      influence the outcomes. In addition, this article describes the auditory training
      protocol used for unilaterally deaf patients. DESIGN: This is a prospective study
      of subjects undergoing cochlear implantation for unilateral deafness with or
      without associated tinnitus. METHODS: Speech perception in noise was tested using
      the Bamford-Kowal-Bench speech-in-noise test presented at 65 dB SPL. The Speech,
      Spatial, and Qualities of Hearing Scale and the Abbreviated Profile of Hearing
      Aid Benefit were used to evaluate the subjective perception of hearing with a
      cochlear implant and quality of life. Tinnitus disturbance was measured using the
      Tinnitus Reaction Questionnaire. Data were collected before cochlear implantation
      and 3, 6, 12, and 24 months after implantation. RESULTS: Twenty-eight postlingual
      unilaterally deaf adults with or without tinnitus were implanted. There was a
      significant improvement in speech perception in noise across time in all spatial
      configurations. There was an overall significant improvement on the subjective
      perception of hearing and quality of life. Tinnitus disturbance reduced
      significantly across time. Age at implantation and duration of deafness did not
      influence the outcomes significantly. CONCLUSION: Cochlear implantation provided
      significant improvement in speech understanding in challenging situations,
      subjective perception of hearing performance, and quality of life. Cochlear
      implantation also resulted in reduced tinnitus disturbance. Age at implantation
      and duration of deafness did not seem to influence the outcomes.

PMID- 25594388
TI  - Stereotactic radiosurgery for facial nerve schwannomas: meta-analysis and
      clinical review.
AB  - OBJECTIVE: Although several small individual series on stereotactic radiosurgery
      (SRS) for facial nerve schwannomas (FNSs) have been published, we aim to
      systematically aggregate data from the literature as well as from our institution
      to better understand the safety and efficacy of SRS for FNS. DATA SOURCES: PubMed
      English language search for keywords "facial nerve schwannoma" AND "radiation
      therapy" published from January 1995 to 2014. Data from our institution were also
      included in the analysis. STUDY SELECTION: Minimum study inclusion criteria
      included tumor treatment outcomes yielding 10 studies in the literature. In
      addition, our institution's data on six patients were included. DATA EXTRACTION:
      Data included radiation treatment type, radiation dose, tumor size, tumor
      control, tumor control definition, FN function, hearing outcome, and duration of
      follow-up. DATA SYNTHESIS: In total, there were 45 patients with at least 2-year
      follow-up. Forty-two patients (93.3%) had tumor control. Of those patients with
      described growth/shrinkage definitions, 50.0% had no growth, 43.3% had shrinkage,
      and 6.7% had growth. Of those articles that included FN functional outcomes, 26
      patients (66.6%) had stable FN function, 8 (20.5%) had improved function, and 5
      (12.8%) had worsened FN function after treatment. In total, there were 30
      patients whose hearing outcomes were discussed in the literature. Of those with
      serviceable hearing before SRS (n = 14), nine (64.3%) had stable hearing and five
      (36.7%) had worsened function after SRS. The mean posttreatment follow-up period
      was 42.1 months. CONCLUSION: SRS seems to be effective at either stabilizing or
      shrinking FNS. However, significant morbidities of FN paralysis hearing loss do
      exist.

PMID- 25594389
TI  - An online database to improve clinical operations and scientific data collection
      in a pediatric hearing loss practice.
AB  - OBJECTIVE: To establish a pediatric hearing loss database that improves
      scientific data collection and clinical workflow in a large pediatric hearing
      loss and cochlear implant practice and incentivizes users to maintain careful
      scientific data collection and entry. PATIENTS: All children with hearing loss
      referred to the study institution. INTERVENTION: A multiuser multistation
      database was designed using a commercial database solution. Electronic data
      previously available were imported and verified. Various groups of professionals
      were educated on proper data entry methods. The database incorporated clinical
      information used in daily practice to ensure routine data entry and verification.
      MAIN OUTCOME MEASURES: Number of children entered into the database; user
      feedback on database feasibility; longitudinal speech perception performance in
      implanted children. RESULTS: Data import proved labor intensive but feasible. New
      data entry was facilitated by the instrument's usefulness in daily practice,
      which was readily accepted by the team involved in the management of pediatric
      hearing loss. Currently, the database includes more than 2,900 pediatric patients
      with hearing impairment, of which 1,034 have cochlear implants. Files contain
      audiometric, speech, anatomic, and surgical data. Speech perception performance
      increased with increasing age and duration of cochlear implant use for 478
      children with speech perception data. CONCLUSION: The present database offers a
      powerful tool for scientific data collection and was easily integrated into the
      institution's busy clinical practice as a minimally time-consuming task. Database
      use facilitated querying for easy application to a number of clinical studies
      from this institution.

PMID- 25594390
TI  - Spectral assignment of new adamantane derivatives of 1,3-; 1,5-dihydroxy- and 1,5
      dimethylnaphthalenes.

PMID- 25594391
TI  - Microwave-promoted tin-free iminyl radical cyclization with TEMPO trapping: a
      practical synthesis of 2-acylpyrroles.
AB  - Microwave-promoted iminyl radical cyclizations can be terminated by trapping with
      TEMPO, affording functionalized adducts. The use of alkynes as radical acceptors
      delivers a range of 2-acylpyrroles in good yields. Toxic and hazardous reagents,
      which are frequently employed in radical reactions, are not required. The O
      phenyl oxime ether substrates are constructed in a single step from readily
      available ketones. 

PMID- 25594396
TI  - Materials research at Shanghai Jiao Tong University.

PMID- 25594392
TI  - Cytotoxic mechanisms of panduratin A on A375 melanoma cells: A quantitative and
      temporal proteomics analysis.
AB  - Melanoma is a lethal form of skin cancer with rising global incidence. However,
      limited treatment options are available for advanced melanoma and this is further
      compounded by the development of resistance toward existing drugs. Panduratin A
      (PA), a cyclohexanyl chalcone found in Boesenbergia rotunda, was investigated for
      its cytotoxic potentials against human malignant melanoma A375 cells. Our initial
      findings revealed that mitochondrion is the primary acting site of PA on A375
      cancer cells and the cytotoxic mechanisms of PA were further investigated using a
      temporal quantitative proteomics approach by iTRAQ 2D-LC-MS/MS. Comprehensive
      proteomics analysis identified 296 proteins that were significantly deregulated
      in PA-treated A375 cells and revealed the involvement of mitochondrial oxidative
      phosphorylation, secretory and ER stress pathway, and apoptosis. We further
      confirmed that the PA-induced apoptosis was mediated by prolonged ER stress at
      least in part via the PERK/eIF2alpha/ATF4/CHOP pathway. Pretreatment with
      cycloheximide, an ER stress inhibitor rescued PA-induced cell death, which was
      accompanied by the suppression of ER-stress-related HSPA5 and CHOP proteins. The
      present study provides comprehensive mechanistic insights into the cytotoxic
      mechanisms of PA. 

PMID- 25594399
TI  - Prenatal diagnosis of orbital melanotic neuroectodermal tumor in infancy.

PMID- 25594381
TI  - Protein lysine acetylation by p300/CBP.

PMID- 25594400
TI  - Controlled electrochemical etching of nanoporous Si anodes and its discharge
      behavior in alkaline Si-air batteries.
AB  - We report the fabrication of nanoporous silicon (nPSi) electrodes via
      electrochemical etching to form a porous Si layer with controllable thickness and
      pore size. Varying the etching time and ethanolic HF concentration results in
      different surface morphologies, with various degrees of electrolyte access
      depending on the pore characteristics. Optimizing the etching condition leads to
      well-developed nPSi electrodes, which have thick porous layers and smaller pore
      diameter and exhibit improved discharge behavior as anodes in alkaline Si-air
      cells in contrast to flat Si anode. Although electrochemical etching is effective
      in improving the interfacial characteristics of Si in terms of high surface area,
      we observed that mild anodization occurs and produces an oxide overlayer. We then
      show that this oxide layer in nPSi anodes can be effectively removed to produce
      an nPSi anode with good discharge behavior in an actual alkaline Si-air cell. In
      the future, the combination of high surface area nPSi anodes with nonaqueous
      electrolytes (e.g., room-temperature ionic liquid electrolyte) to minimize the
      strong passivation behavior and self-discharge in Si could lead to Si-air cells
      with a stable voltage profile and high anode utilization. 

PMID- 25594401
TI  - Study of proton conductivity of a 2D flexible MOF and a 1D coordination polymer
      at higher temperature.
AB  - We report the proton conduction properties of a 2D flexible MOF and a 1D
      coordination polymer having the molecular formulas
      {[Zn(C10H2O8)0.5(C10S2N2H8)].5H2O]}n (1) and {[Zn(C10H2O8)0.5(C10S2N2H8)].2H2O]}n
      (2), respectively. Compounds 1 and 2 show high conductivity values of 2.55 * 10(
      7) and 4.39 * 10(-4) S cm(-1) at 80  degrees C and 95% RH. The conductivity value
      of compound 1 is in the range of those for previously reported flexible MOFs, and
      compound 2 shows the highest proton conductivity among the carboxylate-based 1D
      CPs. The dimensionality and the internal hydrogen bonding connectivity play a
      vital role in the resultant conductivity. Variable-temperature experiments of
      both compounds at high humidity reveal that the conductivity values increase with
      increasing temperature, whereas the variable humidity studies signify the
      influence of relative humidity on high-temperature proton conductivity. The time
      dependent measurements for both compounds demonstrate their ability to retain
      conductivity up to 10 h. 

PMID- 25594402
TI  - Synaptosomal membrane-based Langmuir-Blodgett films: a platform for studies on
      gamma-aminobutyric acid type A receptor binding properties.
AB  - In this work we used Langmuir-Blodgett films (LB) as model membranes to study the
      effect of molecular packing on the flunitrazepam (FNZ) accessibility to the
      binding sites at the GABAA receptor (GABAA-R). Ligand binding data were
      correlated with film topography analysis by atomic force microscopy images (AFM)
      and SDS-PAGE. Langmuir films (LF) were prepared by the spreading of synaptosomal
      membranes (SM) from bovine brain cortex at the air-water interface. LBs were
      obtained by the transference, at 15 or 35 mN/m constant surface pressure (pi), of
      one (LB15/1c and LB35/1c) or two (LB35/2c) LFs to a film-free hydrophobic
      alkylated substrate (CONglass). Transference was performed in a serial manner,
      which allowed the accumulation of a great number of samples. SDS-PAGE clearly
      showed a 55 kDa band characteristic of GABAA-R subunits. Detrended fluctuation
      analysis of topographic data from AFM images exhibited a single slope value (self
      similarity parameter alpha) in CONglass and a discontinuous slope change in the
      alpha value at an autocorrelation length of ~100 nm in all LB samples, supporting
      the LF transference to the substrate. AFM images of CONglass and LB15/1c
      exhibited roughness and average heights that were similar between measurements
      and significantly lower than those of LB35/1c and LB35/2c, suggesting that the
      substrate coverage in the latter was more stable than in LB15/1c. While [(3)H]FNZ
      binding in LB15/1c did not reach saturation, in LB35/1c the binding kinetics
      became sigmoid with a binding affinity lower than in the SM suspension. Our
      results highlight the pi dependence of both binding and topological data and call
      to mind the receptor mechanosensitivity. Thus, LB films provide a tool for
      bionanosensing GABAA-R ligand binding as well as GABAA-R activity modulation
      induced by the environmental supramolecular organization. 

PMID- 25594403
TI  - Controlled release of growth factors for regenerative medicine.
AB  - How to release growth factors (GFs) scientifically to promote stem cell
      proliferation and differentiation is one of the most significant research focuses
      in the field of regenerative medicine. In a controlled release system, growth
      factors, extracellular matrices or biomaterial carriers, and sometimes stem cells
      together form a geometric entirety. Biomaterial carriers provide GFs with a
      support structure to be adhered, immobilized, encapsulated or/and protected. As a
      unity, the release rate and rhythm of GFs on cells are normally very delicate and
      precise. Up to now, the best strategy for clinical applications is the
      combination systems that encapsulate GFs in microspheres, particularly the nano-
      or micro-encapsulation techniques integrated GFs with biomaterial carriers. In
      this mini review, we summarize the current progress in GF delivery systems for
      regenerative medicine and provide an outlook on two main aspects: one is the
      classes of stem cells and GFs that have been used frequently in regenerative
      medicine, including their respective application conditions and functions; the
      other is the controlled GF release systems, in which various GFs are released
      orderly and continuously without diffusing simply and rapidly, including their
      respective opportunities and challenges. 

PMID- 25594404
TI  - Application of 3D biomimetic models in drug delivery and regenerative medicine.
AB  - Regenerative medicine holds much promise in assisting patients to recover from
      injured or lost tissues and organs through organism reconstruction. Three
      dimensional (3D) biomimetic models via various approaches can be used by
      pharmaceutical industry for controlled drug delivery. With proper biomaterials
      and engineering technologies, drugs can be released in a rate-manipulated manner
      towards targeted regions with spatial and temporal effects. Much of the success
      is a result of a combination of growth factors, stem cells, biomaterials,
      nanotechnologies, electrospinning and 3D printing techniques mimicking in vivo
      angiogenesis, histogenesis and tumorigenesis processes. This interdisciplinary
      field on biomimetic drug delivery and regenerative medicine has already opened up
      a new avenue for medical progress and reformation. This article presents a
      comprehensive review of the 3D biomimetic models in the pertinent fields of
      tissue and organ manufacturing, cell-material mutual interactions, bioactive
      agent carrier systems and anti-cancer drug delivery methods. Particularly, the
      potential trends and challenges of tissue and organ manufacturing are discussed
      from different perspectives. 

PMID- 25594405
TI  - 2D, 3D and 4D active compound delivery in tissue engineering and regenerative
      medicine.
AB  - Recent advances in tissue engineering and regenerative medicine have shown that
      controlling cells microenvironment during growth is a key element to the
      development of successful therapeutic system. To achieve such control,
      researchers have first proposed the use of polymeric scaffolds that were able to
      support cellular growth and, to a certain extent, favor cell organization and
      tissue structure. With nowadays availability of a large pool of stem cell lines,
      such approach has appeared to be rather limited since it does not offer the fine
      control of the cell micro-environment in space and time (4D). Therefore,
      researchers are currently focusing their efforts on developing strategies that
      include active compound delivery systems in order to add a fourth dimension to
      the design of 3D scaffolds. This review will focus on recent concepts and
      applications of 2D and 3D techniques that have been used to control the load and
      release of active compounds used to promote cell differentiation and
      proliferation in or out of a scaffold. We will first present recent advances in
      the design of 2D polymeric scaffolds and the different techniques that have been
      used to deposit molecular cues and cells in a controlled fashion. We will
      continue presenting the recent advances made in the design of 3D scaffolds based
      on hydrogels as well as polymeric fibers and we will finish by presenting some of
      the research avenues that are still to be explored. 

PMID- 25594406
TI  - Systemic drug delivery systems for bone tissue regeneration- a mini review.
AB  - Musculoskeletal metabolic diseases such as osteoporosis have become the major
      public health problems worldwide in our aging society. Pharmaceutical therapy is
      one of the approaches to prevent and treat related medical conditions. Most of
      the clinically used anti-osteoporotic drugs are administered systemically and
      have demonstrated some side effects in non-skeletal tissues. One of the
      innovative approaches to prevent potential adverse effects is the development of
      bone-targeting drug delivery technologies that not only minimizes the systemic
      toxicity but also improves the pharmacokinetic profile and therapeutic efficacy
      of chemical drugs. This paper reviews the currently available bone targeting drug
      delivery systems with emphasis as bone-targeting moieties, including the
      bonesurface- site-specific (bone formation dominant or bone resorption dominant)
      and cell-specific moieties. In addition, the connections of drug-bone-targeting
      moieties-carrier are also summarized, and the newly developed liposomes and
      nanoparticles are discussed for their potential use and main challenges in
      delivering therapeutic agents to bone tissue. As a rapid-developing
      biotechnology, systemic bonetargeting delivery system is promising but still in
      its infancy where challenges are ahead of us, including the stability and the
      toxicity issues, especially to fulfill the regulatory requirement to realize
      bench-to-bedside translation. Newly developed biomaterials and technologies with
      potential for safer and more effective drug delivery require multidisciplinary
      collaborations with preclinical and clinical scientists that are essential to
      facilitate their clinical applications. 

PMID- 25594407
TI  - Multifunctional therapeutic delivery strategies for effective neuro-regeneration
      following traumatic spinal cord injury.
AB  - Traumatic Spinal Cord Injuries (TSCI), due to their devastating nature, present
      several interventional challenges (extensive inflammation, axonal tethering, scar
      formation, neuronal degeneration and functional loss) that need to be addressed
      before even a slight neuronal recovery can be achieved. Recent post-TSCI
      investigational approaches include a combination of "support and therapeutic"
      strategies capable of providing localized delivery of therapeutic molecules along
      with specialized architecture to allow axonal growth and conformal repair. This
      review provides a brief overview of multifunctional therapeutic delivery
      strategies for effective neuroregeneration post-TSCI with special emphasis on
      intrathecal hydrogel-based injectable systems, chondroitinase ABC releasing
      matrices, micro/nano-sized particulate strategies, 3D-scaffold architectures,
      biopolymeric channeled bridges for directed neuronal growth, functionalized nerve
      conduits, nano- and micro-fibrous scaffolds and multicomponent combinatorial
      paradigms for localized delivery to spinal cord. In addition; a comprehensive
      account of most widely employed macromolecules and the related neuro
      pharmacological, -anatomical, and -functionaloutcomes conferred by the
      abovementioned neural tissue engineering approaches is provided. Furthermore, the
      performance of individual delivery systems towards the enhancement of
      effectiveness, efficiency, and stability of therapeutic molecules and
      neurotrophic factors is discussed. In conclusion, it is suggested that a
      multifunctional combinatorial device assimilating the biomaterial, cellular,
      molecular, structural and functional aspects altogether is the best way forward
      for effective neuroregeneration post-TSCI. 

PMID- 25594408
TI  - Strategies for recruitment of stem cells to treat myocardial infarction.
AB  - Heart failure is one of the most prominent causes of morbidity and mortality
      worldwide. According to the World Health Organization, coronary artery disease
      and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI
      results in obstruction of the blood supply to the heart and scar formation, and
      causes substantial death of cardiomyocytes in the infarct zone followed by an
      inflammatory response. Current treatment methodologies of MI and heart failure
      include organ transplantation, coronary artery bypass grafting, ventricular
      remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies
      has associated risks and benefits. Cellular cardiomyoplasty is a viable option to
      decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and
      improve heart function. However, the low rate of cell survival, shortage of cell
      sources and donors, tumorigenesis, and ethical issues hamper full exploitation of
      cell therapy for MI treatment. Consequently, the mobilization and recruitment of
      endogenous stem/progenitor cells from bone marrow, peripheral circulation, and
      cardiac tissues has immense potential through harnessing the host's own
      reparative capacities that result from interplay among cytokines, chemokines, and
      adhesion molecules. Therapeutic treatments to enhance the mobilization and homing
      of stem cells are under development. In this review, we present state-of-the-art
      approaches that are being pursued for stem cell mobilization and recruitment to
      regenerate infarcted myocardium. Potential therapeutic interventions and delivery
      strategies are discussed in detail. 

PMID- 25594409
TI  - Bioactive hydrogel scaffolds - advances in cartilage regeneration through
      controlled drug delivery.
AB  - The importance of growth factor delivery in cartilage tissue engineering is
      nowadays widely recognized. However, when growth factors are administered by a
      bolus injection, they undergo rapid clearance before they could stimulate the
      cells of interest at promoting cartilage repair. Their short half-lives make
      growth factors ineffective, unless administered at supraphysiological doses, with
      potentially harmful consequences on patient safety. Recently, new tissue
      engineering strategies relying on the combination of biodegradable scaffolds and
      specific biological cues, such as growth or adhesive factors or genetic material,
      have demonstrated that controlled release is the key factor for achieving
      effective cartilage repair at lower drug doses. Among all biomaterials, hydrogels
      have emerged as promising cartilage tissue engineering scaffolds for simultaneous
      cell growth and drug delivery. In fact, hydrogels can be easily loaded with cells
      and drugs, that are subsequently released in a controlled fashion. The success of
      hydrogels in controlled drug delivery for tissue engineering originates from
      their biocompatibility and capacity to integrate well with the host tissue. This
      review overviews the hydrogels technologies now available for the regeneration of
      cartilage that base their efficacy on the controlled release of bioactive
      substances able to modulate cellular behavior and to eventually lead to
      successful tissue repair. 

PMID- 25594410
TI  - DSPE-PEG: a distinctive component in drug delivery system.
AB  - 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE-
      PEG) is a widely used phospholipids-polymer conjugate in drug delivery
      applications. It is a biocompatible, biodegradable and amphiphilic material which
      can also be functionalized with various biomolecules for specific functions. With
      the emerging interest in use of nanocarriers for therapeutic drug delivery and
      imaging DSPE-PEG has become a very useful material for the formulation of these
      nanocarriers for achieving prolonged blood circulation time, improved stability
      and enhanced encapsulation efficiency. This review will focus on the
      relationships between the structure of DSPEPEG and its noticeable effects on
      these nanocarriers' properties, and the recent progress on the development of
      DSPE-PEG and its derivatives in delivery systems. 

PMID- 25594411
TI  - Reconstituted high density lipoprotein-based nanoparticles: an overview of
      applications in regenerative medicine, preparation, evaluation and future trends.
AB  - Reconstituted high density lipoprotein (rHDL) is an excellent and highly
      biocompatible nanovector mimicking the physical, chemical as well as
      physiological properties of native high density lipoprotein (HDL), and is
      originally widely used as the substitute in HDL related studies. Over the past
      decades, rHDL has increasingly been exploited into vehicles for targeted delivery
      of numerous drugs, therapeutic genes, etc., and is playing a more and more
      important role in drug delivery design for regenerative medicine. As such, a
      systematic review of this promising carrier will be of great importance for
      subsequent studies. In this article, the term "rHDL-based nanoparticles
      (rHDLbased NPs)" is employed to refer to rHDL and its modified form. This review
      highlights four aspects of rHDL-based NPs: current applications in regenerative
      medicine, preparation methods, conventional evaluation methods, and future trends
      on co-delivery of drugs for synergic effects. 

PMID- 25594412
TI  - Material couture for wound healing and regeneration: an overview.
AB  - Wound healing is a complex regenerative process of great importance in clinical
      medicine, controlled by temporal interactions between cells, extracellular matrix
      components and signalling molecules. Localised delivery of therapeutic active
      agents viz. antimicrobials, soothing minerals and/or vitamins and growth factors
      at the site of injury/trauma/wound are expected to be more effective and will
      always manifest milder toxic concerns than those observed upon systemic
      administration of these agents. Since ancient times, search is on for suitable
      materials which may restore or reproduce a favourable and a natural milieu
      required for skin regeneration, so as to prevent infections, and make the process
      fast and less painful. The journey started with the use of natural materials with
      a simple function of covering or dressing the wounds to more advanced materials
      of present times, which are designed for specific and extraordinary functions.
      Natural and modified or synthetic polymers; alone or in combination are commonly
      used as dressing (couture) materials for wound healing. This article offers a
      review of materials that have been used to design and develop wound dressings. 

PMID- 25594413
TI  - 3D Printing technology over a drug delivery for tissue engineering.
AB  - Many researchers have attempted to use computer-aided design (CAD) and computer
      aided manufacturing (CAM) to realize a scaffold that provides a three-dimensional
      (3D) environment for regeneration of tissues and organs. As a result, several 3D
      printing technologies, including stereolithography, deposition modeling, inkjet
      based printing and selective laser sintering have been developed. Because these
      3D printing technologies use computers for design and fabrication, and they can
      fabricate 3D scaffolds as designed; as a consequence, they can be standardized.
      Growth of target tissues and organs requires the presence of appropriate growth
      factors, so fabrication of 3Dscaffold systems that release these biomolecules has
      been explored. A drug delivery system (DDS) that administrates a pharmaceutical
      compound to achieve a therapeutic effect in cells, animals and humans is a key
      technology that delivers biomolecules without side effects caused by excessive
      doses. 3D printing technologies and DDSs have been assembled successfully, so new
      possibilities for improved tissue regeneration have been suggested. If the
      interaction between cells and scaffold system with biomolecules can be understood
      and controlled, and if an optimal 3D tissue regenerating environment is realized,
      3D printing technologies will become an important aspect of tissue engineering
      research in the near future. 

PMID- 25594414
TI  - Copper tolerance mechanisms of Mesorhizobium amorphae and its role in aiding
      phytostabilization by Robinia pseudoacacia in copper contaminated soil.
AB  - The legume-rhizobium symbiosis has been proposed as an important system for
      phytoremediation of heavy metal contaminated soils due to its beneficial activity
      of symbiotic nitrogen fixation. However, little is known about metal resistant
      mechanism of rhizobia and the role of metal resistance determinants in
      phytoremediation. In this study, copper resistance mechanisms were investigated
      for a multiple metal resistant plant growth promoting rhizobium, Mesorhizobium
      amorphae 186. Three categories of determinants involved in copper resistance were
      identified through transposon mutagenesis, including genes encoding a P-type
      ATPase (CopA), hypothetical proteins, and other proteins (a GTP-binding protein
      and a ribosomal protein). Among these determinants, copA played the dominant role
      in copper homeostasis of M. amorphae 186. Mutagenesis of a hypothetical gene lipA
      in mutant MlipA exhibited pleiotropic phenotypes including sensitivity to copper,
      blocked symbiotic capacity and inhibited growth. In addition, the expression of
      cusB encoding part of an RND-type efflux system was induced by copper. To explore
      the possible role of copper resistance mechanism in phytoremediation of copper
      contaminated soil, the symbiotic nodulation and nitrogen fixation abilities were
      compared using a wild-type strain, a copA-defective mutant, and a lipA-defective
      mutant. Results showed that a copA deletion did not affect the symbiotic capacity
      of rhizobia under uncontaminated condition, but the protective role of copA in
      symbiotic processes at high copper concentration is likely concentration
      dependent. In contrast, inoculation of a lipA-defective strain led to significant
      decreases in the functional nodule numbers, total N content, plant biomass and
      leghemoglobin expression level of Robinia pseudoacacia even under conditions of
      uncontaminated soil. Moreover, plants inoculated with lipA-defective strain
      accumulated much less copper than both the wild-type strain and the copA
      defective strain, suggesting an important role of a healthy symbiotic
      relationship between legume and rhizobia in phytostabilization. 

PMID- 25594416
TI  - "Catch-and-release" of HNO with pyrazolones.
AB  - A new and versatile class of HNO donors, the (hydroxylamino)pyrazolone (HAPY)
      series of HNO donors utilizing pyrazolone (PY) leaving groups, is described. HNO,
      the smallest N-based aldehyde equivalent, is used as a reagent along with a
      variety of PY compounds to synthesize the desired HAPY donors in what can be
      considered an N-selective HNO-aldol reaction in up to quantitative yields. The
      bimolecular rate constant of HNO with PY in pH 7.4 phosphate buffer at 37 
      degrees C can reach 8 * 10(5) M(-1) s(-1). In (1)H NMR experiments, the HAPY
      compounds generate HNO quantitatively (trapped as a phosphine aza-ylide) with
      half-lives spanning 3 orders of magnitude (minutes to days) under physiologically
      relevant conditions. B3LYP/6-31G* calculations confirm the energetically
      favorable reactions between HNO and the PY enol and enolate, whereas HNO release
      is expected to occur through the oxyanion (OHN-PY) of each HAPY compound. HNO has
      been shown to provide functional support to failing hearts. 

PMID- 25594417
TI  - Conceptual issues in autism spectrum disorders.
AB  - PURPOSE OF REVIEW: To provide an update on recent studies concerning social
      cognition in autism spectrum disorders (ASDs), to compare different theoretical
      approaches used to interpret empirical data, and to highlight a number of
      conceptual issues. RECENT FINDINGS: In regard to social cognition in ASDs, there
      is an emerging emphasis on early-onset and prolonged sensory-motor problems. Such
      sensory-motor problems may fit with the theories of social cognition that
      emphasize the importance of embodied interaction rather than deficits in
      mindreading, or they may reflect more general aspects of developmental disorders.
      SUMMARY: Different theoretical frameworks offer alternative perspectives on the
      central characteristics in ASDs and motivate different ways of conceptualizing
      diagnosis and intervention. Theory-of-mind approaches continue to appeal to false
      belief paradigms, and debate continues about the performance of individuals with
      autism. Likewise, there is continuing debate and renewed skepticism about the
      role of simulation and deficits in the mirror system in ASDs. Growing evidence
      concerning sensory-motor problems, specifically disrupted patterns in re-entrant
      (afferent and proprioceptive) sensory feedback across the autistic spectrum, may
      not only provide support for more embodied interactive approaches, but also
      suggests that a single approach is unlikely able to explain all social cognition
      problems in autism. A pluralist approach understands ASDs as involving a variant
      range of cascading disrupted processes.

PMID- 25594415
TI  - Role of protein farnesylation in burn-induced metabolic derangements and insulin
      resistance in mouse skeletal muscle.
AB  - OBJECTIVE: Metabolic derangements, including insulin resistance and
      hyperlactatemia, are a major complication of major trauma (e.g., burn injury) and
      affect the prognosis of burn patients. Protein farnesylation, a posttranslational
      lipid modification of cysteine residues, has been emerging as a potential
      component of inflammatory response in sepsis. However, farnesylation has not yet
      been studied in major trauma. To study a role of farnesylation in burn-induced
      metabolic aberration, we examined the effects of farnesyltransferase (FTase)
      inhibitor, FTI-277, on burn-induced insulin resistance and metabolic alterations
      in mouse skeletal muscle. METHODS: A full thickness burn (30% total body surface
      area) was produced under anesthesia in male C57BL/6 mice at 8 weeks of age. After
      the mice were treated with FTI-277 (5 mg/kg/day, IP) or vehicle for 3 days,
      muscle insulin signaling, metabolic alterations and inflammatory gene expression
      were evaluated. RESULTS: Burn increased FTase expression and farnesylated
      proteins in mouse muscle compared with sham-burn at 3 days after burn.
      Simultaneously, insulin-stimulated phosphorylation of insulin receptor (IR),
      insulin receptor substrate (IRS)-1, Akt and GSK-3beta was decreased. Protein
      expression of PTP-1B (a negative regulator of IR-IRS-1 signaling), PTEN (a
      negative regulator of Akt-mediated signaling), protein degradation and lactate
      release by muscle, and plasma lactate levels were increased by burn. Burn-induced
      impaired insulin signaling and metabolic dysfunction were associated with
      increased inflammatory gene expression. These burn-induced alterations were
      reversed or ameliorated by FTI-277. CONCLUSIONS: Our data demonstrate that burn
      increased FTase expression and protein farnesylation along with insulin
      resistance, metabolic alterations and inflammatory response in mouse skeletal
      muscle, all of which were prevented by FTI-277 treatment. These results indicate
      that increased protein farnesylation plays a pivotal role in burn-induced
      metabolic dysfunction and inflammatory response. Our study identifies FTase as a
      novel potential molecular target to reverse or ameliorate metabolic derangements
      in burn patients.

PMID- 25594418
TI  - Costs and benefits of realism and optimism.
AB  - PURPOSE OF REVIEW: What is the relationship between rationality and mental
      health? By considering the psychological literature on depressive realism and
      unrealistic optimism, it was hypothesized that, in the context of judgments about
      the self, accurate cognitions are psychologically maladaptive and inaccurate
      cognitions are psychologically adaptive. Recent studies recommend being cautious
      in drawing any general conclusion about the style of thinking and mental health.
      RECENT FINDINGS: Recent investigations suggest that people with depressive
      symptoms are more accurate than controls in tasks involving time perception and
      estimates of personal circumstances, but not in other tasks. Unrealistic optimism
      remains a robust phenomenon across a variety of tasks and domains, and
      researchers are starting to explore its neural bases. However, the challenge is
      to determine to what extent and in what way unrealistic optimism is beneficial.
      SUMMARY: We should revisit the hypothesis that optimistic cognitions are
      psychologically adaptive, whereas realistic thinking is not. Realistic beliefs
      and expectations can be conducive to wellbeing and good functioning, and wildly
      optimistic cognitions have considerable psychological costs.

PMID- 25594419
TI  - Conceptual issues in 'cognitive impairment'.
AB  - PURPOSE OF REVIEW: This review aims to set out the recent writings relevant to
      acquired cognitive impairment in an attempt to reveal some of the underlying
      conceptual issues. RECENT FINDINGS: The huge strides being taken to diagnose
      Alzheimer's and other dementias early, including pre-symptomatically, raise
      important ethical issues. But there are broader conceptual issues too, around the
      notion of normal ageing. New techniques, such as deep brain stimulation, raise
      further ethical concerns, but may be relevant to deeper philosophical issues.
      Meanwhile, capacity continues to be of interest to researchers in the field of
      cognitive impairment, but the 'United Nations Convention on the Rights of Persons
      with Disabilities' is raising questions about our understanding of the nature of
      capacity. These new ideas reflect shifts in our understanding of personhood. How
      we think about the person is relevant to how we think about dilemmas over
      artificial nutrition and is also pertinent to debates about rational suicide in
      response to a diagnosis of dementia. A person-centred view allows us to think
      more broadly about cognitive impairment. SUMMARY: Cognitive impairment challenges
      us to think broadly, to see such impairment as something to be dealt with in the
      context of our multifaceted life-worlds.

PMID- 25594420
TI  - Smell identification function and Alzheimer's disease: a selective review.
AB  - PURPOSE OF REVIEW: To provide an update of the recent studies on the olfactory
      function in Alzheimer's disease, with a focus on the olfactory identification
      function. RECENT FINDINGS: The studies reviewed here confirm previous reports on
      the poor olfactory function in Alzheimer's disease compared to health normal
      controls and also as a marker for conversion from mild cognitive impairment to
      Alzheimer's disease. Olfactory identification function has been associated with
      severity of illness, non-cognitive neuropsychiatric symptoms, and structural and
      functional MRI measures. There is a possible interaction of apolipoprotein E
      genotype with olfactory performance in Alzheimer's disease patients and those at
      risk for Alzheimer's disease. Usefulness of smell identification function in
      differentiating Alzheimer's disease patients from other types of dementia needs
      to be established. SUMMARY: The need for simple, inexpensive and non-invasive
      procedures for aiding in the diagnosis and understanding of Alzheimer's disease
      has led to theories and procedures examining the role of olfactory functions in
      Alzheimer's disease. Although there is increasing evidence for olfactory
      dysfunction in general and impaired odour identification in particular in
      Alzheimer's disease, additional larger and methodologically sound research is
      needed for testing its clinical utility in day-to-day clinical practice for
      early, accurate and differential diagnosis of Alzheimer's disease.

PMID- 25594421
TI  - Family adjustment and interventions in neurodevelopmental disorders.
AB  - PURPOSE OF REVIEW: Developmental disabilities are increasingly recognized, and
      remarkable progress is being made on the genetic and neurobiological
      underpinnings of many disorders. Yet, only a tiny percentage of the disability
      literature addresses families of children with disabilities. A review of recently
      published family studies reveals salient trends and gaps. RECENT FINDINGS:
      Consistent with previous work, high levels of parent stress, illness, anxiety,
      and depression are apparent. Studies in the USA focused on parents of children
      with autism; in contrast, studies on parents of children with intellectual
      disabilities were almost always conduced abroad. Compared to other disabilities,
      families of children with psychiatric disorders and genetic syndromes are
      understudied. The majority of family studies are descriptive, with very few
      trials or interventions aimed at reducing parental stress. Of these, mindfulness
      practices and a peer-mentor model of treatment delivery hold much promise for
      effective stress reduction. Psychoeducational programs and respite care are
      differentially beneficial. SUMMARY: A new era of family intervention research is
      in order. This work can take advantage of many advances in telemedicine, peer
      mentor models, smart technology, and biomarkers as indices of change. Benefit
      could also stem from group interventions with parents who share similar concerns,
      regardless of their child's diagnostic label.

PMID- 25594423
TI  - Effects of enamel matrix derivative and transforming growth factor-beta1 on
      connective tissue growth factor in human periodontal ligament fibroblasts.
AB  - BACKGROUND: Enamel matrix derivative (EMD) is suggested to stimulate transforming
      growth factor-beta (TGF-beta) production. Connective tissue growth factor (CTGF)
      is a downstream mediator of TGF-beta. This study explores the effects of EMD and
      TGF-beta1 on CTGF in periodontal ligament (PDL) fibroblasts and their
      interactions in PDL proliferation and development. METHODS: Human PDL cells were
      stimulated with EMD. To explore the effects of EMD and TGF-beta1 on CTGF
      expression, cells were treated with and without TGF-beta inhibitor, and CTGF
      protein levels were assayed by Western blot analysis. To study the role of CTGF
      in PDL development, cells were treated with CTGF inhibitor. DNA synthesis was
      analyzed by bromodeoxyuridine enzyme-linked immunosorbent assay. Reverse
      transcription polymerase chain reaction was performed to examine messenger RNA
      expression of PDL osteoblastic differentiation markers: type I collagen, alkaline
      phosphatase, and osteocalcin. RESULTS: EMD induced a concentration-dependent
      increase of CTGF protein expression in PDL cells. EMD- and TGF-beta1-stimulated
      CTGF expression was significantly reduced in the presence of TGF-beta inhibitor.
      CTGF inhibition downregulated both EMD- and TGF-beta1-induced DNA synthesis. The
      effect of CTGF and EMD on osteoblastic mRNA expression in PDL cells is not
      obvious. CONCLUSIONS: EMD stimulates CTGF expression in human PDL cells, a
      process modulated by the TGF-beta pathway. CTGF can affect EMD- and TGF-beta1
      induced PDL cell proliferation, but its effects on PDL with regard to
      osteoblastic differentiation remain inconclusive. The results provide novel
      insights into EMD-CTGF interaction in PDL cells.

PMID- 25594422
TI  - Study of nanostructural organization of ionic liquids by electron paramagnetic
      resonance spectroscopy.
AB  - The X-band electron paramagnetic resonance spectroscopy (EPR) of a stable,
      spherical nitroxide spin probe, perdeuterated 2,2,6,6-tetramethyl-4-oxopiperidine
      1-oxyl (pDTO) has been used to study the nanostructural organization of a series
      of 1-alkyl-3-methylimidazolium tetrafluoroborate ionic liquids (ILs) with alkyl
      chain lengths from two to eight carbons. By employing nonlinear least-squares
      fitting of the EPR spectra, we have obtained values of the rotational correlation
      time and hyperfine coupling splitting of pDTO to high precision. The rotational
      correlation time of pDTO in ILs and squalane, a viscous alkane, can be fit very
      well to a power law functionality with a singular temperature, which often
      describes a number of physical quantities measured in supercooled liquids. The
      viscosity of the ILs and squalane, taken from the literature, can also be fit to
      the same power law expression, which means that the rotational correlation times
      and the ionic liquid viscosities have similar functional dependence on
      temperature. The apparent activation energy of both the rotational correlation
      time of pDTO and the viscous flow of ILs and squalane increases with decreasing
      temperature; in other words, they exhibit strong non-Arrhenius behavior. The
      rotational correlation time of pDTO as a function of eta/T, where eta is the
      shear viscosity and T is the temperature, is well described by the Stokes
      Einstein-Debye (SED) law, while the hydrodynamic probe radii are solvent
      dependent and are smaller than the geometric radius of the probe. The temperature
      dependence of hyperfine coupling splitting is the same in all four ionic liquids.
      The value of the hyperfine coupling splitting starts decreasing with increasing
      alkyl chain length in the ionic liquids in which the number of carbons in the
      alkyl chain is greater than four. This decrease together with the decrease in the
      hydrodynamic radius of the probe indicates a possible existence of nonpolar
      nanodomains. 

PMID- 25594424
TI  - Association of serum 17beta-estradiol concentration, hormone therapy, and
      alveolar crest height in postmenopausal women.
AB  - BACKGROUND: Declines in endogenous estrogen levels after menopause can lead to
      systemic bone loss, including loss of oral bone and alveolar crest height (ACH).
      However, few studies have assessed both serum 17beta-estradiol (E2) and exogenous
      hormone therapy (HT) use in relation to oral bone loss. METHODS: This study
      examines the associations among serum E2, HT use, and ACH in 613 postmenopausal
      women from the Buffalo OsteoPerio study. Baseline ACH levels and 5-year ACH were
      assessed for groups according to E2 level (undetectable, >5.00 to <=18.00, >18.00
      to <=46.07, and >46.07 pg/mL) and among HT use (never, ever) using analysis of
      variance and analysis of covariance. Logistic regression was used to analyze the
      association of ACH loss with serum E2 and HT use. RESULTS: In cross-sectional
      analyses, no association was found of serum E2 with whole-mouth mean or worst
      site ACH. However, history of HT use was associated with ACH. Women who had never
      used HT had more ACH loss assessed as a whole-mouth mean ACH (P = 0.01) and as
      worst-site ACH loss (P = 0.03). In logistic regression analyses of baseline ACH
      loss severity, HT never-users had two-fold higher odds of being in the severe ACH
      loss category compared to ever-users (odds ratio, 2.00; 95% confidence interval,
      1.11 to 3.62). No association was observed of 5-year change in ACH with baseline
      serum E2 or HT use. CONCLUSION: Although this study did not detect an association
      with current serum E2 level and ACH, HT use was found to be associated with less
      ACH loss in postmenopausal women.

PMID- 25594425
TI  - Effect of living cellular sheets on the angiogenic potential of human
      microvascular endothelial cells.
AB  - BACKGROUND: A fundamental issue limiting the efficacy of surgical approaches
      designed to correct periodontal mucogingival defects is that new tissues rely on
      limited sources of blood supply from the adjacent recipient bed. Accordingly,
      therapies based on tissue engineering that leverage local self-healing potential
      may represent promising alternatives for the treatment of mucogingival defects by
      inducing local vascularization. The aim of this study is to evaluate the effect
      of commercially available living cellular sheets (LCS) on the angiogenic
      potential of neonatal dermal human microvascular endothelial cells (HMVEC-dNeo).
      METHODS: The effect of LCS on HMVEC-dNeo proliferation, migration, capillary tube
      formation, gene expression, and production of angiogenic factors was evaluated
      over time. RESULTS: LCS positively influenced HMVEC-dNeo proliferation and
      migration. Moreover, HMVEC-dNeo incubated with LCS showed transcriptional
      profiles different from those of untreated cells. Whereas increased expression of
      angiogenic genes predominated early on in response to LCS, late-phase responses
      were characterized by up- and downregulation of angiostatic and angiogenic genes.
      However, this trend was not confirmed at the protein level, as LCS induced
      increased production of most of the angiogenic factors tested (i.e., epidermal
      growth factor [EGF], heparin-binding EGF-like growth factor, interleukin 6,
      angiopoietin, platelet-derived growth factor-BB, placental growth factor, and
      vascular endothelial growth factor) throughout the investigational period.
      Finally, although LCS induced HMVEC-dNeo proliferation, migration, and expression
      of angiogenic factors, additional factors and environmental pressures are likely
      to be required to promote the development of complex, mesh-like vascular
      structures. CONCLUSION: LCS favor initial mechanisms that govern angiogenesis but
      failed to enhance or accelerate HMVEC-dNeo morphologic transition to complex
      vascular structures.

PMID- 25594426
TI  - Sensitivity and specificity of radiographic methods for predicting insertion
      torque of dental implants.
AB  - BACKGROUND: Subjective radiographic classifications of alveolar bone have been
      proposed and correlated with implant insertion torque (IT). The present
      diagnostic study aims to identify quantitative bone features influencing IT and
      to use these findings to develop an objective radiographic classification for
      predicting IT. METHODS: Demographics, panoramic radiographs (taken at the
      beginning of dental treatment), and cone-beam computed tomographic scans (taken
      for implant surgical planning) of 25 patients receiving 31 implants were
      analyzed. Bone samples retrieved from implant sites were assessed with dual x-ray
      absorptiometry, microcomputed tomography, and histology. Odds ratio, sensitivity,
      and specificity of all variables to predict high peak IT were assessed. RESULTS:
      A ridge cortical thickness >0.75 mm and a normal appearance of the inferior
      mandibular cortex were the most sensitive variables for predicting high peak IT
      (87.5% and 75%, respectively). A classification based on the combination of both
      variables presented high sensitivity (90.9%) and specificity (100%) for
      predicting IT. CONCLUSIONS: Within the limitations of this study, the results
      suggest that it is possible to predict IT accurately based on radiographic
      findings of the patient. This could be useful in the treatment plan of immediate
      loading cases.

PMID- 25594427
TI  - Topical TrkA Kinase Inhibitor CT327 is an Effective, Novel Therapy for the
      Treatment of Pruritus due to Psoriasis: Results from Experimental Studies, and
      Efficacy and Safety of CT327 in a Phase 2b Clinical Trial in Patients with
      Psoriasis.
AB  - Pruritus is an important symptom in psoriasis with no targeted treatment.
      Tropomyosin-receptor kinase A (TrkA) is associated with pruritus and psoriatic
      plaque formation. We report the efficacy of a TrkA inhibitor, CT327, on pruritus
      in psoriasis. A randomised, double-blind, vehicle-controlled Phase 2b clinical
      trial was conducted in 160 subjects. No effect was found on psoriasis severity
      using Investigator's Global Assessment (primary endpoint). However, clinically
      and statistically significant reductions in pruritus were observed in the 108
      patient subset reporting at least moderate pruritus at baseline (37.1 mm visual
      analogue scale improvement (95% CI [-37.5, -6.2], p = 0.0067) for lowest dose;
      secondary endpoint). Significant modified Psoriasis Area and Severity Index
      reductions were found in this subset (p < 0.05). Experiments exploring capsaicin
      mediated calcium influx, important in pruritus signalling, were performed in
      sensory neurons. CT327 inhibited capsaicin responses, indicating action at the
      nerve growth factor-TrkA-TRPV1 pathway. TrkA is a key target in pruritus, and
      CT327 has potential to become an effective and safe first-in-class treatment.

PMID- 25594428
TI  - A thematic analysis of experiences of varicose veins and minimally invasive
      surgery under local anaesthesia.
AB  - AIMS AND OBJECTIVES: To gain insight into the experience of living with varicose
      veins and undergoing minimally invasive surgery under local anaesthesia in a
      private clinic. BACKGROUND: Minimally invasive surgery under local anaesthesia is
      replacing traditional surgical stripping for the treatment for varicose veins.
      Conscious surgery has previously been associated with elevated levels of anxiety
      and some associated pain. There is limited research exploring the experiences of
      patients undergoing varicose vein surgery under local anaesthesia. DESIGN:
      Qualitative semi-structured interviews with 20 patients who took part in a mixed
      methods study exploring the effects of distraction on intra-operative pain and
      anxiety. METHODS: Participants were interviewed eight weeks post surgery about
      their experiences before, during and after surgery. Interviews were analysed
      using thematic analysis. RESULTS: Four themes were captured (1) negative emotions
      associated with symptoms, (2) unpreparedness for the surgical process, (3)
      feeling cared for and (4) improvements in well-being. An overarching theme of
      relationships was identified. Overall, varicose veins had a detrimental impact on
      quality of life prior to surgery. Patients felt unprepared for their procedure
      and experienced the operation as anxiety provoking and uncomfortable. This was
      much helped by the support of nursing staff in the theatre. Post surgery,
      patients' quality of life was reported as improved. CONCLUSIONS: More emphasis
      needs to be placed on preparing patients for surgery under local anaesthesia. The
      role of the nurse is central to creating a caring, relaxed environment which
      could improve patient experience. RELEVANCE TO CLINICAL PRACTICE: Patients'
      experiences of varicose veins and their treatment both influence, and are
      influenced by relationships with others at all stages of the management process.
      Nurses play an important role in improving patient experience during surgery and
      care needs to be taken to ensure that patients understand and accept the
      processes of surgery and recovery.

PMID- 25594429
TI  - Potential application of interventional endoscopic ultrasonography for the
      treatment of esophageal and gastric varices.
AB  - Interventional endoscopic ultrasonography (EUS) has been developed mainly for the
      treatment of pancreaticobiliary disorders (e.g. cyst drainage for pancreatic
      pseudocysts, biliary drainage for malignant biliary obstruction, and celiac
      plexus neurolysis). Recently, the application of interventional EUS has been
      expanded to a new field, the treatment of gastrointestinal varices. There have
      been several studies examining this new technique for the treatment of esophageal
      and gastric varices. In the present review, we have summarized the current status
      of interventional EUS for the treatment of esophageal and gastric varices (e.g.
      EUS-guided coil deployment for gastric varices) and clarified the clinical
      feasibility of this procedure. 

PMID- 25594430
TI  - Echocardiographic evaluation of myocardial changes observed after closure of
      patent ductus arteriosus in dogs.
AB  - BACKGROUND: Closure of PDA can be associated with echocardiographic changes
      including deterioration of LV systolic function. Although PDA is commonly
      encountered in dogs, few comprehensive reports of echocardiographic changes in
      dogs with PDA closure are available. OBJECTIVES: To evaluate the short-term
      echocardiographic changes observed after PDA closure in dogs using strain
      analysis. ANIMALS: Seventeen client-owned dogs with left-to-right PDA. METHODS:
      Echocardiographic evaluations, including standard echocardiography and two
      dimensional tissue tracking (2DTT), were performed before and within 3 days of
      PDA closure. RESULTS: Preclosure examination showed LV and left atrial dilatation
      indicating volume overload as a result of PDA. Closure of PDA resulted in
      significant reduction of LVIDd (<.0001) and LA/Ao (0.01) without change in LVIDs,
      suggestive of decreased preload. Postclosure LV systolic dysfunction was observed
      with significant decreased in FS (<.0001) and strain values (P = .0039 for radial
      strains, P = .0005 for circumferential strains). Additionally, significant LV
      dyssynchrony (P = .0162) was observed after closure of PDA. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Closure of PDA resulted in decreased preload as a result of
      alleviation of LV volume overload, which in turn caused transient deterioration
      of LV systolic function. Additionally, this study demonstrated that strain
      analysis is load dependent. Therefore, care should be taken when interpreting
      strain measurements as an indicator of LV systolic function.

PMID- 25594432
TI  - Reply to Pollock (2014) Comments on 'Saddleback deformities in yellowfin bream,
      Acanthopagrus australis (Gunther), from South East Queensland' by Diggles (2013).

PMID- 25594433
TI  - Peptide nanoparticle delivery of charge-neutral splice-switching morpholino
      oligonucleotides.
AB  - Oligonucleotide analogs have provided novel therapeutics targeting various
      disorders. However, their poor cellular uptake remains a major obstacle for their
      clinical development. Negatively charged oligonucleotides, such as 2'-O-Methyl
      RNA and locked nucleic acids have in recent years been delivered successfully
      into cells through complex formation with cationic polymers, peptides, liposomes,
      or similar nanoparticle delivery systems. However, due to the lack of
      electrostatic interactions, this promising delivery method has been unsuccessful
      to date using charge-neutral oligonucleotide analogs. We show here that lipid
      functionalized cell-penetrating peptides can be efficiently exploited for
      cellular transfection of the charge-neutral oligonucleotide analog
      phosphorodiamidate morpholino. The lipopeptides form complexes with splice
      switching phosphorodiamidate morpholino oligonucleotide and can be delivered into
      clinically relevant cell lines that are otherwise difficult to transfect while
      retaining biological activity. To our knowledge, this is the first study to show
      delivery through complex formation of biologically active charge-neutral
      oligonucleotides by cationic peptides. 

PMID- 25594434
TI  - Multinight "bedside" closed-loop control for patients with type 1 diabetes.
AB  - BACKGROUND: Studies of closed-loop control (CLC) systems have improved glucose
      levels in patients with type 1 diabetes. In this study we test a new CLC concept
      aiming to "reset" the patient overnight to near-normoglycemia each morning, for
      several consecutive nights. SUBJECTS AND METHODS: Ten insulin pump users with
      type 1 diabetes (mean age, 46.4+/-8.5 years) were enrolled in a two-center (in
      the United States and Italy) randomized crossover trial comparing 5 consecutive
      nights of CLC (23:00-07:00 h) in an outpatient setting versus sensor-augmented
      insulin pump therapy of the same duration at home. Primary end points included
      time spent in 80-140 mg/dL as measured by continuous glucose monitoring overnight
      and fasting blood glucose distribution at 7:00 h. RESULTS: Compared with sensor
      augmented pump therapy, CLC improved significantly time spent between 80 and 140
      mg/dL (54.5% vs. 32.2%; P<0.001) and between 70 and 180 mg/dL (85.4% vs. 59.1%;
      P<0.001); CLC reduced the mean glucose level at 07:00 h (119.3 vs. 152.9 mg/dL;
      P<0.001) and overnight mean glucose level (139.0 vs. 170.3 mg/dL; P<0.001) using
      a marginally lower amount of insulin (6.1 vs. 6.8 units; P=0.1). Tighter
      overnight control led to improved daytime control on the next day: the
      overnight/next-day control correlation was r=0.52, P<0.01. CONCLUSIONS:
      Multinight CLC of insulin delivery (artificial pancreas) results in significant
      improvement in morning and overnight glucose levels and time in target range,
      with the potential to improve daytime control when glucose levels were "reset" to
      near-normoglycemia each morning.

PMID- 25594435
TI  - Comparison of intraductal ultrasonography findings between primary sclerosing
      cholangitis and IgG4-related sclerosing cholangitis.
AB  - BACKGROUND AND AIM: Comparisons of intraductal ultrasonography (IDUS) findings
      between primary sclerosing cholangitis (PSC) and IgG4-related sclerosing
      cholangitis (IgG4-SC) have not been elucidated. We aimed to clarify the
      differences in transpapillary IDUS findings between PSC and IgG4-SC. METHODS: We
      retrospectively compared transpapillary IDUS findings between 15 patients with
      PSC and 35 patients with IgG4-SC between 2004 and 2014. RESULTS: IDUS findings of
      circular-asymmetric wall thickness, irregular inner margin, diverticulum-like
      outpouching, unclear outer margin, heterogeneous internal echo, and disappearance
      of three layers were significantly higher in PSC than in IgG4-SC (P < 0.001).
      Irregular inner margin, diverticulum-like outpouching, and disappearance of three
      layers were specific IDUS findings for PSC compared to IgG4-SC. Diverticulum-like
      outpouching on IDUS and endoscopic retrograde cholangiogram (ERC) was observed in
      10 (67%) and five (33%) of 15 patients with PSC, respectively. However, based on
      IDUS and ERC, diverticulum-like outpouching was not observed in any patient with
      IgG4-SC. All five patients with diverticulum-like outpouching on ERC had
      diverticulum-like outpouching on IDUS, and five (50%) of 10 patients without
      diverticulum-like outpouching on ERC had diverticulum-like outpouching on IDUS.
      CONCLUSIONS: The IDUS findings differed between PSC and IgG4-SC. Irregular inner
      margin, diverticulum-like outpouching, and disappearance of three layers are
      specific IDUS findings for PSC compared to IgG4-SC. IDUS is a more useful
      procedure than ERC for the early detection of diverticulum-like outpouching.

PMID- 25594431
TI  - TAM receptor signaling in immune homeostasis.
AB  - The TAM receptor tyrosine kinases (RTKs)-TYRO3, AXL, and MERTK-together with
      their cognate agonists GAS6 and PROS1 play an essential role in the resolution of
      inflammation. Deficiencies in TAM signaling have been associated with chronic
      inflammatory and autoimmune diseases. Three processes regulated by TAM signaling
      may contribute, either independently or collectively, to immune homeostasis: the
      negative regulation of the innate immune response, the phagocytosis of apoptotic
      cells, and the restoration of vascular integrity. Recent studies have also
      revealed the function of TAMs in infectious diseases and cancer. Here, we review
      the important milestones in the discovery of these RTKs and their ligands and the
      studies that underscore the functional importance of this signaling pathway in
      physiological immune settings and disease. 

PMID- 25594436
TI  - Implications of High Molecular Divergence of Nuclear rRNA and Phylogenetic
      Structure for the Dinoflagellate Prorocentrum (Dinophyceae, Prorocentrales).
AB  - The small and large nuclear subunit molecular phylogeny of the genus Prorocentrum
      demonstrated that the species are dichotomized into two clades. These two clades
      were significantly different (one-factor ANOVA, p < 0.01) with patterns
      compatible for both small and large subunit Bayesian phylogenetic trees, and for
      a larger taxon sampled dinoflagellate phylogeny. Evaluation of the molecular
      divergence levels showed that intraspecies genetic variations were significantly
      low (t-test, p < 0.05), than those for interspecies variations (> 2.9% and >
      26.8% dissimilarity in the small and large subunit [D1/D2], respectively). Based
      on the calculated molecular divergence, the genus comprises two genetically
      distinct groups that should be considered as two separate genera, thereby setting
      the pace for major systematic changes for the genus Prorocentrum sensu Dodge.
      Moreover, the information presented in this study would be useful for improving
      species identification, detection of novel clades from environmental samples.

PMID- 25594437
TI  - Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric
      Aortic Valve Interstitial Cells within 3D Engineered Matrices.
AB  - Living tissue-engineered heart valves (TEHV) would be a major benefit for
      children who require a replacement with the capacity for growth and biological
      integration. A persistent challenge for TEHV is accessible human cell source(s)
      that can mimic native valve cell phenotypes and matrix remodeling characteristics
      that are essential for long-term function. Mesenchymal stem cells derived from
      bone marrow (BMMSC) or adipose tissue (ADMSC) are intriguing cell sources for
      TEHV, but they have not been compared with pediatric human aortic valve
      interstitial cells (pHAVIC) in relevant 3D environments. In this study, we
      compared the spontaneous and induced multipotency of ADMSC and BMMSC with that of
      pHAVIC using different induction media within three-dimensional (3D) bioactive
      hybrid hydrogels with material modulus comparable to that of aortic heart valve
      leaflets. pHAVIC possessed some multi-lineage differentiation capacity in
      response to induction media, but limited to the earliest stages and much less
      potent than either ADMSC or BMMSC. ADMSC expressed cell phenotype markers more
      similar to pHAVIC when conditioned in basic fibroblast growth factor (bFGF)
      containing HAVIC growth medium, while BMMSC generally expressed similar
      extracellular matrix remodeling characteristics to pHAVIC. Finally, we covalently
      attached bFGF to PEG monoacrylate linkers and further covalently immobilized in
      the 3D hybrid hydrogels. Immobilized bFGF upregulated vimentin expression and
      promoted the fibroblastic differentiation of pHAVIC, ADMSC, and BMMSC. These
      findings suggest that stem cells retain a heightened capacity for osteogenic
      differentiation in 3D culture, but can be shifted toward fibroblast
      differentiation through matrix tethering of bFGF. Such a strategy is likely
      important for utilizing stem cell sources in heart valve tissue engineering
      applications. 

PMID- 25594439
TI  - Dietary strategies for the treatment of cadmium and lead toxicity.
AB  - Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health
      effects in humans and animals. Chelation therapy, the conventional treatment for
      heavy metal toxicity, is reported to have a number of safety and efficacy issues.
      Recent studies have shown that dietary supplements play important roles in
      protecting against Cd and Pb toxicity. This paper reviews the evidence for
      protective effects of essential metals, vitamins, edible plants, phytochemicals,
      probiotics and other dietary supplements against Cd and Pb toxicity and describes
      the proposed possible mechanisms. Based on these findings, dietary strategies are
      recommended for people at risk of Cd and Pb exposure. The application of these
      strategies is advantageous for both the prevention and alleviation of Cd and Pb
      toxicity, as such supplements can be added easily and affordably to the daily
      diet and are expected to have very few side effects compared to the chelation
      therapy. 

PMID- 25594440
TI  - The relevance of the colon to zinc nutrition.
AB  - Globally, zinc deficiency is widespread, despite decades of research highlighting
      its negative effects on health, and in particular upon child health in low-income
      countries. Apart from inadequate dietary intake of bioavailable zinc, other
      significant contributors to zinc deficiency include the excessive intestinal loss
      of endogenously secreted zinc and impairment in small intestinal absorptive
      function. Such changes are likely to occur in children suffering from
      environmental (or tropical) enteropathy (EE)-an almost universal condition among
      inhabitants of developing countries characterized by morphologic and functional
      changes in the small intestine. Changes to the proximal gut in environmental
      enteropathy will likely influence the nature and amount of zinc delivered into
      the large intestine. Consequently, we reviewed the current literature to
      determine if colonic absorption of endogenous or exogenous (dietary) zinc could
      contribute to overall zinc nutriture. Whilst we found evidence that significant
      zinc absorption occurs in the rodent colon, and is favoured when microbially
      fermentable carbohydrates (specifically resistant starch) are consumed, it is
      unclear whether this process occur in humans and/or to what degree. Constraints
      in study design in the few available studies may well have masked a possible
      colonic contribution to zinc nutrition. Furthermore these few available human
      studies have failed to include the actual target population that would benefit,
      namely infants affected by EE where zinc delivery to the colon may be increased
      and who are also at risk of zinc deficiency. In conducting this review we have
      not been able to confirm a colonic contribution to zinc absorption in humans.
      However, given the observations in rodents and that feeding resistant starch to
      children is feasible, definitive studies utilising the dual stable isotope method
      in children with EE should be undertaken. 

PMID- 25594443
TI  - Challenges of working and living in a new cultural environment: A snapshot of
      international medical graduates in rural Tasmania.
AB  - OBJECTIVES: To highlight the experiences and challenges of international medical
      graduates (IMGs) living and working in rural and remote Tasmania, and how this
      informs their acculturation and retention in the state. DESIGN: This paper
      reports the findings from the Tasmanian IMG questionnaire, which was administered
      both in hardcopy and online format to all known IMGs within the state. A total of
      105 questionnaires were returned, representing a response rate of 30.0%. RESULTS:
      IMGs were from the 30 countries and the majority were under 49 years of age, had
      migrated in the past 10 years, with over half having worked in the state for less
      than 2 years. Many IMGs indicated that they were satisfied with their current
      employment, the medical facilities, the friendliness of their patients and the
      friendliness of the community where they lived, and would like to stay much
      longer in Tasmania. CONCLUSIONS: Many IMGs have previously lived and worked in
      rural areas and are reasonably satisfied with their current employment and
      lifestyle in Tasmania. However, the following factors play an important part in
      their views and attitudes: employment satisfaction, access to schools, employment
      for spouse or partner and access to cultural or religious foods and goods.
      Nevertheless, beyond employment satisfaction, employment itself, coupled with
      career pathway and training opportunities, were highlighted as contributory
      factors for leaving Tasmania.

PMID- 25594442
TI  - Dabigatran adherence in atrial fibrillation patients during the first year after
      diagnosis: a nationwide cohort study.
AB  - BACKGROUND: There is a perception among physicians that lack of routine
      monitoring with non-vitamin K antagonist oral anticoagulants (NOACs) may lead to
      poor adherence to medication. We studied adherence during the first year of usage
      in a cohort of patients with newly diagnosed non-valvular atrial fibrillation
      (AF) started on the NOAC, dabigatran etexilate. METHODS AND RESULTS: Nationwide
      Danish patient and prescription purchase registries were used to identify newly
      diagnosed AF patients taking dabigatran, comorbidities, and refill patterns under
      a twice-daily, one pill regimen. Adherence was characterized among remaining
      users (N = 2960) after 1 year using the proportion of days covered (PDC), gap
      rates and restart rates. The overall 1-year PDC was 83.9%, with 76.8% of patients
      having a 1-year PDC in excess of 80%. Patients with a CHA2 DS2 -VASc score >= 2
      were more adherent to medication regimes than patients with a CHA2 DS2 -VASc
      score of 1 (PDC ratio, 1.12; 95% confidence interval [CI], 1.08-1.17) and
      generally patients with higher morbidity showed more adherence. Patients with
      prior bleeding were not less adherent to medication regimes than patients with no
      prior bleeding (PDC ratio, 1.02; 95% CI, 0.98-1.06). The overall gap rate was 1.4
      gaps per year. There were no clear tendencies in gap rates among subgroups,
      although patients with higher morbidity tended to have slightly more, but
      shorter, gap periods. CONCLUSIONS: More than 75% of patients were showed > 80%
      adherence to medication regimes during the first year. Patients with higher
      morbidity, including patients with a higher risk of stroke or bleeding, exhibited
      better adherence. This improvement may be attributable to more regular contact
      with the healthcare system.

PMID- 25594441
TI  - Dietary patterns and maternal anthropometry in HIV-infected, pregnant Malawian
      women.
AB  - Diet is a modifiable factor that can contribute to the health of pregnant women.
      In a sample of 577 HIV-positive pregnant women who completed baseline interviews
      for the Breastfeeding, Antiretrovirals, and Nutrition Study in Lilongwe, Malawi,
      cluster analysis was used to derive dietary patterns. Multiple regression
      analysis was used to identify associations between the dietary patterns and mid
      upper arm circumference (MUAC), arm muscle area (AMA), arm fat area (AFA), and
      hemoglobin at baseline. Three key dietary patterns were identified: animal-based,
      plant-based, and grain-based. Women with relatively greater wealth were more
      likely to consume the animal-based diet, which had the highest intake of energy,
      protein, and fat and was associated with higher hemoglobin levels compared to the
      other diets. Women with the lowest wealth were more likely to consume the grain
      based diet with the lowest intake of energy, protein, fat, and iron and were more
      likely to have lower AFA than women on the animal-based and plant-based diets,
      but higher AMA compared to women on the animal-based diet. Pregnant, HIV-infected
      women in Malawi could benefit from nutritional support to ensure greater nutrient
      diversity during pregnancy, when women face increased nutrient demands to support
      fetal growth and development. 

PMID- 25594444
TI  - Trends in breastfeeding initiation in the NICU by gestational age in Ohio, 2006
      2012.
AB  - BACKGROUND: While breastfeeding in the United States is on the rise, trends among
      infants admitted to the Neonatal Intensive Care Unit (NICU) are less known. The
      objective of this study was to examine trends in breastfeeding initiation among
      NICU-admitted infants in Ohio from 2006 to 2012 and to determine differences in
      breastfeeding initiation trends by gestational age. METHODS: Using Ohio Vital
      Statistics birth certificate data, the Cochran-Armitage test for trend was used
      to determine significant trends in breastfeeding by gestational age. Logistic
      regression was used to examine the association between breastfeeding initiation
      and gestational age by year. RESULTS: From 2006 to 2012, 48,758 infants born in
      Ohio were admitted to the NICU, representing 5.6 percent of all newborns.
      Breastfeeding among NICU-admitted infants increased from 53.3 percent in 2006 to
      63.8 percent in 2012 (p < 0.01). Increasing, significant trends in breastfeeding
      were also observed within each gestational age category over the 7 years. In 2011
      and 2012, preterm infants were significantly more likely than term infants to be
      fed breastmilk in the NICU. DISCUSSION: The gap between breastfeeding initiation
      among NICU-admitted and non-admitted infants appears to be narrowing,
      particularly for the most extreme gestational ages. While these increasing trends
      in breastfeeding among the most premature infants are encouraging, nearly 40
      percent of mothers of term infants admitted to the NICU, the largest proportion
      of the NICU population, are still not initiating breastfeeding. More education
      and support specific to mothers of infants admitted to the NICU is needed.

PMID- 25594445
TI  - Anticoagulation for portal vein thrombosis in cirrhosis: Response to Naeshiro and
      collaborators.

PMID- 25594438
TI  - Nutritionally-induced catch-up growth.
AB  - Malnutrition is considered a leading cause of growth attenuation in children.
      When food is replenished, spontaneous catch-up (CU) growth usually occurs,
      bringing the child back to its original growth trajectory. However, in some
      cases, the CU growth is not complete, leading to a permanent growth deficit. This
      review summarizes our current knowledge regarding the mechanism regulating
      nutrition and growth, including systemic factors, such as insulin, growth
      hormone, insulin- like growth factor-1, vitamin D, fibroblast growth factor-21,
      etc., and local mechanisms, including autophagy, as well as regulators of
      transcription, protein synthesis, miRNAs and epigenetics. Studying the molecular
      mechanisms regulating CU growth may lead to the establishment of better
      nutritional and therapeutic regimens for more effective CU growth in children
      with malnutrition and growth abnormalities. It will be fascinating to follow this
      research in the coming years and to translate the knowledge gained to clinical
      benefit. 

PMID- 25594446
TI  - Interprofessional collaboration in research, education, and clinical practice:
      working together for a better future.
AB  - Interprofessional collaboration occurs when 2 or more professions work together
      to achieve common goals and is often used as a means for solving a variety of
      problems and complex issues. The benefits of collaboration allow participants to
      achieve together more than they can individually, serve larger groups of people,
      and grow on individual and organizational levels. This editorial provides an
      overview of interprofessional collaboration in the areas of clinical practice,
      education, and research; discusses barriers to collaboration; and suggests
      potential means to overcome them. 

PMID- 25594448
TI  - Oral health: foreword.

PMID- 25594447
TI  - Anisotropic intrinsic lattice thermal conductivity of phosphorene from first
      principles.
AB  - Phosphorene, the single layer counterpart of black phosphorus, is a novel two
      dimensional semiconductor with high carrier mobility and a large fundamental
      direct band gap, which has attracted tremendous interest recently. Its potential
      applications in nano-electronics and thermoelectrics call for fundamental study
      of the phonon transport. Here, we calculate the intrinsic lattice thermal
      conductivity of phosphorene by solving the phonon Boltzmann transport equation
      (BTE) based on first-principles calculations. The thermal conductivity of
      phosphorene at 300 K is 30.15 W m(-1) K(-1) (zigzag) and 13.65 W m(-1) K(-1)
      (armchair), showing an obvious anisotropy along different directions. The
      calculated thermal conductivity fits perfectly to the inverse relationship with
      temperature when the temperature is higher than Debye temperature (ThetaD =
      278.66 K). In comparison to graphene, the minor contribution around 5% of the ZA
      mode is responsible for the low thermal conductivity of phosphorene. In addition,
      the representative mean free path (MFP), a critical size for phonon transport, is
      also obtained. 

PMID- 25594449
TI  - Oral health: prevention of dental disease.
AB  - Good oral health is integral to optimum overall health. Unfortunately, almost one
      fourth of the US population has untreated dental caries, and most individuals do
      not seek or have access to regular dental care. Untreated dental disease can
      cause or exacerbate chronic medical conditions, lead to unnecessary pain, and
      increase costs to the medical system. Risk factors for poor dental health include
      diets high in sugar, inappropriate bottle feeding of infants, and low fluoride
      levels in the community's water supply. Regular and thorough tooth brushing with
      fluoridated toothpaste at least twice daily can help keep teeth healthy. Routine
      use of fluoride varnishes on primary teeth, along with fluoride supplementation
      when concentrations in the primary water supply are inadequate, can help prevent
      caries. Dental care visits at professionally determined risk-based intervals can
      lead to improved oral health by preventing new and mitigating existing dental
      disease. Avoidance or cessation of tobacco use also is recommended. 

PMID- 25594451
TI  - Oral health: orthodontic treatment.
AB  - Improper tooth alignment due to crowding, malocclusion, and missing teeth can
      cause difficulties with eating and speech, and premature wear. It is estimated
      that more than 20% of children would benefit from orthodontic treatment to
      correct these conditions, many of which will persist into adulthood if not
      corrected. Orthodontic care is gaining popularity among adults for similar
      concerns, as well as for correction of cosmetic issues. The psychological effects
      of malocclusion should not be ignored. The American Association of Orthodontists
      recommends that all children undergo evaluation at the first recognition of an
      orthodontic condition and no later than age 7 years. Some children will need
      early treatment to help eliminate developing conditions and improve the
      foundations of the bite, which can ease later treatment in adolescence. For
      others, treatment in adolescence without early treatment is recommended. Standard
      cemented braces or clear, removable aligners may be used, depending on the
      patient's corrective needs. Average treatment time is approximately 2 years; this
      may be shortened by the use of accelerative techniques. Routine preventive dental
      care should be continued during the treatment period. 

PMID- 25594450
TI  - Oral health: treatment of dental trauma and pain.
AB  - Dental trauma is common among adults and children. As children become mobile,
      they frequently experience trauma to their primary teeth because of falls.
      Injuries to permanent teeth are common results of falls, motor vehicle accidents,
      sports injuries, and violence. Trauma can affect the tooth enamel, dentin, pulp,
      root, periodontal ligament, gum, or alveolar bone. Avulsions are characterized by
      complete displacement of the tooth from the socket. Avulsed primary teeth should
      not be replanted because replantation is associated with a risk of damage to the
      developing permanent tooth. Avulsed permanent teeth are considered a dental
      emergency and should be replanted by the first individual capable of doing so. If
      immediate replantation is not possible, the tooth should be stored in cold animal
      or human milk; it also can be stored in the mouth, adjacent to the buccal mucosa,
      if the patient is capable of doing so. Water should be avoided as a storage
      medium because it impedes healing of the periodontal ligament, but storage in
      water is superior to dry storage. Intruded teeth (ie, pushed into the jaw) may
      need immediate extraction, depending on their orientation. All patients with
      dental trauma should follow up promptly with a dentist. Patients presenting with
      chronic dental pain without an obvious treatable etiology will benefit from
      ongoing support from their family physicians. 

PMID- 25594452
TI  - Oral health: dentures and dental implants.
AB  - More than 35 million Americans have lost all of their teeth, and 178 million are
      missing at least one tooth. Left unmanaged, tooth loss, or edentulism, can lead
      to nutritional deficiencies, oral pain, and poor psychosocial functioning. The
      family physician may be the first clinician to discuss tooth loss as a health
      concern with the patient. A patient who is interested in replacing missing teeth
      may be a candidate for dentures, implants, or a combination of these. The
      patient's preferences, general health, degree of edentulism, ability to follow up
      regularly, smoking status, and overall oral health should be considered when the
      prosthodontist makes recommendations for treatment. Smoking can delay tissue
      healing; therefore, heavy smoking may be a contraindication to implant placement.
      If a patient chooses dentures, the family physician should perform regular oral
      examinations, because up to 70% of denture wearers are affected by denture
      stomatitis at some point. Poor fit, poor hygiene, nighttime wearing of removable
      dentures, and bacterial or candidal infections can all be identified and managed
      by the family physician. The physician also can reinforce proper wear and care
      instructions for dentures and proper care of implants. 

PMID- 25594454
TI  - Immunology careers at the NIH, FDA and CDC: different paths that focus on
      advancing public health.

PMID- 25594453
TI  - Deficiency of prolactin-inducible protein leads to impaired Th1 immune response
      and susceptibility to Leishmania major in mice.
AB  - Although the strategic production of prolactin-inducible protein (PIP) at several
      ports of pathogen entry into the body suggests it might play a role in host
      defense, no study has directly implicated it in immunity against any infectious
      agent. Here, we show for the first time that PIP deficiency is associated with
      reduced numbers of CD4(+) T cells in peripheral lymphoid tissues and impaired
      CD4(+) Th1-cell differentiation in vitro. In vivo, CD4(+) T cells from OVA
      immunized, PIP-deficient mice showed significantly impaired proliferation and IFN
      gamma production following in vitro restimulation. Furthermore, PIP-deficient
      mice were highly susceptible to Leishmani major infection and failed to control
      lesion progression and parasite proliferation. This susceptibility was associated
      with impaired NO production and leishmanicidal activity of PIP KO macrophages
      following IFN-gamma and LPS stimulation. Collectively, our findings implicate PIP
      as an important regulator of CD4(+) Th1-cell-mediated immunity. 

PMID- 25594455
TI  - Inflammatory ILC2 cells: disguising themselves as progenitors?

PMID- 25594456
TI  - Broad and strong: the ultimate antibody to dengue virus.

PMID- 25594457
TI  - GPR15: a tale of two species.

PMID- 25594458
TI  - PTENtiating autoimmunity through Treg cell deregulation.

PMID- 25594471
TI  - Air-pressure tunable depletion width, rectification behavior, and charge
      conduction in oxide nanotubes.
AB  - Metal-oxide nanotubes provide large surface areas and functionalizable surfaces
      for a variety of optical and electronic applications. Here we report air-tunable
      rectifying behavior, depletion width modulation, and two-dimensional (2D) charge
      conduction in hollow titanium-dioxide nanotubes. The metal contact forms a
      Schottky-diode in the nanotubes, and the rectification factor (on/off ratio) can
      be varied by more than 3 orders of magnitude (1-2 * 10(3)) as the air pressure is
      increased from 2 mTorr to atmospheric pressure. This behavior is explained using
      a change in depletion width of these thin nanotubes by adsorption of water vapor
      on both surfaces of a hollow nanotube, and the resulting formation of a metal
      insulator-semiconductor (MIS) junction, which controls the 2D charge conduction
      properties in thin oxide nanotubes. 

PMID- 25594472
TI  - Electronic health record workflow: why more work than flow?

PMID- 25594473
TI  - Person- and family-centered care: a time for reflection.

PMID- 25594474
TI  - A case for the use of validated physiological mortality metrics to guide early
      family intervention in intensive care unit patients.
AB  - In the current health care climate a large portion of health care dollars are
      spent in the final months of life, so ensuring that care provided is in line with
      the wishes of patients and their families is more critical than ever. On the one
      hand, surviving families often report that they wish they had been given
      prognostic information earlier and that, in retrospect, they would have made
      different treatment decisions if they had been given prognostic information. On
      the other hand, providers often are reluctant to discuss prognosis for various
      reasons, not the least of which is the inherently uncertain nature of
      prognostication. To address this issue, this article reviews pertinent literature
      about provider reticence, family preference, and the move toward palliative care
      and includes a discussion of the various validated mortality-prediction models
      available. A case is made to use those validated metrics to guide early
      discussions of palliative or end-of-life care for patients who are critically
      ill. A suggested checklist to facilitate inclusion of prognosis discussions in
      family meetings is included as well as a case study to illustrate the problem,
      current practice, and a model for improvement. 

PMID- 25594476
TI  - A collaborative critical care preceptorship for APRN students.
AB  - Advanced practice registered nurses (APRNs) increasingly are caring for
      critically ill patients as a part of interprofessional teams, but new APRNs may
      have limited critical care exposure in their training. We created a 12-week
      critical care preceptorship for APRN students as well as a curriculum composed of
      daily case-based teaching. Student assessment methods included direct
      observation, pretests and posttests of critical care knowledge, and presurveys
      and postsurveys of perceptions about critical care skills. The average score on
      the knowledge pretest was 50% and increased to 74% on the posttest (N = 10).
      Students reported increased comfort in several aspects of managing critically ill
      patients after the preceptorship. Descriptive feedback noted that the
      preceptorship is distinctive, comprehensive, and focused on student education.
      The evolving intensive care unit will have increasing numbers of APRNs, and a
      collaborative preceptorship can improve critical care know-ledge and perceptions
      of critical care skills in APRN students. 

PMID- 25594465
TI  - Pathophysiology of T follicular helper cells in humans and mice.
AB  - Follicular helper T cells (TFH cells) compose a heterogeneous subset of CD4(+) T
      cells that induce the differentiation of B cells into plasma cells and memory
      cells. They are found within and in proximity to germinal centers in secondary
      lymphoid organs, and their memory compartment also circulates in the blood. Our
      knowledge on the biology of TFH cells has increased significantly during the past
      decade, largely as a result of mouse studies. However, recent studies on human
      TFH cells isolated from lymphoid organ and blood samples and recent observations
      on the developmental mechanism of human TFH cells have revealed both similarities
      and differences between human and mouse TFH cells. Here we present the
      similarities and differences between mouse and human lymphoid organ-resident TFH
      cells and discuss the role of TFH cells in response to vaccines and in disease
      pathogenesis. 

PMID- 25594477
TI  - Demonstrating the value of clinical nurse specialists in acute and critical care.

PMID- 25594478
TI  - Role of the clinical nurse specialist in improving patient outcomes after cardiac
      surgery.
AB  - Health care reform continues to focus on improving patient outcomes while
      reducing costs. Clinical nurse specialists (CNSs) should facilitate this process
      to ensure that best practice standards are used and patient safety is enhanced.
      One example of ensuring best practices and patient safety is early extubation
      after open heart surgery, which is a critical component of fast track protocols
      that reduces may reduce the development of pulmonary complications in the
      postoperative period while decreasing overall length of stay in the hospital.
      This project was an interdisciplinary endeavor, led by the CNS and nurse manager,
      which combined early extubation protocols with enhanced rounding initiatives to
      help decrease overall length of ventilation time as well as reduce pulmonary
      complications in patients in the cardiac surgery intensive care unit. The project
      resulted in a significant decrease in length of stay and a decrease in pulmonary
      complications in the postoperative period. 

PMID- 25594480
TI  - Role of the clinical nurse specialist in the journey to magnet recognition.
AB  - Clinical nurse specialists (CNSs) work with and through other nurses as well as
      interprofessional team members to advance nursing practice, improve outcomes, and
      provide clinical expertise to effect system-wide changes to improve programs of
      care. They practice across the continuum and through 3 spheres of influence,
      encompassing the patient, nurse, and system. Clinical nurse specialists possess
      expertise in developing and refining structures, strategies, and processes to
      optimize outcomes at both the unit (micro) level and the organization or system
      (macro) level. This unique vantage point positions CNSs as ideal individuals to
      assume several key roles when a health care organization makes the decision to
      embark on the Magnet journey and to maintain Magnet recognition. The competence
      and competencies of CNSs and a health care organization's desire to achieve
      and/or maintain Magnet recognition represent a synergistic match. 

PMID- 25594479
TI  - Using a scorecard to demonstrate clinical nurse specialists' contributions.
AB  - Clinical nurse specialists (CNSs) have the expertise to influence change at the
      patient, nurse, and system levels. They are clinical experts who understand the
      challenges of the current health care environment: decreasing costs, ensuring
      high-quality care, and achieving outcomes. Evidence has demonstrated CNSs'
      influence on improving patient outcomes. Although CNSs often lead the work, they
      can be invisible when the outcomes are presented. A scorecard to display this
      work could be invaluable to the CNS role, as it would bring transparency to the
      evidence-based work done. This article describes the development of a CNS
      scorecard in a 627-bed tertiary hospital. 

PMID- 25594481
TI  - Clinical nurse specialist regulation: the Maryland experience.
AB  - High-quality care will continue to be a driver in the evolution of today's health
      care environment. Ensuring effective, cost-conscious, quality care is the core of
      clinical nurse specialist (CNS) practice. The CNS practice varies by state,
      depending on each state's Nurse Practice Act. Some states have separate scopes of
      practice for CNSs, including prescriptive authority, whereas some states do not
      recognize CNS practice as different from the practice of the registered nurse.
      The journey to state recognition and title protection for the CNS role in the
      state of Maryland is described. 

PMID- 25594482
TI  - Ethical issues in caring for patients with Ebola: implications for critical care
      nurses.

PMID- 25594484
TI  - Wandering atrial pacemaker and multifocal ectopic atrial tachycardia.

PMID- 25594485
TI  - Simultaneous electrical-field-effect modulation of both top and bottom Dirac
      surface states of epitaxial thin films of three-dimensional topological
      insulators.
AB  - It is crucial for the studies of the transport properties and quantum effects
      related to Dirac surface states of three-dimensional topological insulators (3D
      TIs) to be able to simultaneously tune the chemical potentials of both top and
      bottom surfaces of a 3D TI thin film. We have realized this in molecular beam
      epitaxy-grown thin films of 3D TIs, as well as magnetic 3D TIs, by fabricating
      dual-gate structures on them. The films could be tuned between n-type and p-type
      by each gate alone. Combined application of two gates can reduce the carrier
      density of a TI film to a much lower level than with only one of them and enhance
      the film resistance by 10,000%, implying that Fermi level is tuned very close to
      the Dirac points of both top and bottom surface states without crossing any bulk
      band. The result promises applications of 3D TIs in field effect devices.

PMID- 25594486
TI  - Program of arithmetic improvement by means of cognitive enhancement: an
      intervention in children with special educational needs.
AB  - This study reports the cognitive and arithmetic improvement of a mathematical
      model based on the program PASS Remedial Program (PREP), which aims to improve
      specific cognitive processes underlying academic skills such as arithmetic. For
      this purpose, a group of 20 students from the last four grades of Primary
      Education was divided into two groups. One group (n=10) received training in the
      program and the other served as control. Students were assessed at pre and post
      intervention in the PASS cognitive processes (planning, attention, simultaneous
      and successive processing), general level of intelligence, and arithmetic
      performance in calculus and solving problems. Performance of children from the
      experimental group was significantly higher than that of the control group in
      cognitive process and arithmetic. This joint enhancement of cognitive and
      arithmetic processes was a result of the operationalization of training that
      promotes the encoding task, attention and planning, and learning by induction,
      mediation and verbalization. The implications of this are discussed. 

PMID- 25594487
TI  - Mass spectrometry-based cDNA profiling as a potential tool for human body fluid
      identification.
AB  - Several mRNA markers have been exhaustively evaluated for the identification of
      human venous blood, saliva, and semen in forensic genetics. As new candidate
      human body fluid specific markers are discovered, evaluated, and reported in the
      scientific literature, there is an increasing trend toward determining the ideal
      markers for cDNA profiling of body fluids of forensic interest. However, it has
      not been determined which molecular genetics-based technique(s) should be
      utilized to assess the performance of these markers. In recent years, only a few
      confirmatory, mRNA/cDNA-based methods have been evaluated for applications in
      body fluid identification. The most frequently described methods tested to date
      include quantitative polymerase chain reaction (qPCR) and capillary
      electrophoresis (CE). However these methods, in particular qPCR, often favor
      narrow multiplex PCR due to the availability of a limited number of fluorescent
      dyes/tags. In an attempt to address this technological constraint, this study
      explored matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF MS) for human body fluid identification via cDNA
      profiling of venous blood, saliva, and semen. Using cDNA samples at 20pg input
      phosphoglycerate kinase 1 (PGK1) amounts, body fluid specific markers for the
      candidate genes were amplified in their corresponding body fluid (i.e., venous
      blood, saliva, or semen) and absent in the remaining two (100% specificity). The
      results of this study provide an initial indication that MALDI-TOF MS is a
      potential fluorescent dye-free alternative method for body fluid identification
      in forensic casework. However, the inherent issues of low amounts of mRNA, and
      the damage caused to mRNA by environmental exposures, extraction processes, and
      storage conditions are important factors that significantly hinder the
      implementation of cDNA profiling into forensic casework.

PMID- 25594488
TI  - Identification of layers in optical coherence tomography of skin: comparative
      analysis of experimental and Monte Carlo simulated images.
AB  - BACKGROUND/PURPOSE: The goal of the study is comparative analysis of the layers
      in OCT images and the morphological structure of skin with thick and thin
      epidermis. METHODS: We analyzed the difference between skin with thin and thick
      epidermis in two ways. The first approach consisted in determination of the
      thicknesses of layers of skin with thin and thick epidermis of different
      localizations from experimental OCT images. The second approach was to develop
      numerical models fitting experimental OCT images based on Monte Carlo simulations
      revealing structure and optical parameters of layers of skin with thick and thin
      epidermis. RESULTS: The correspondence between the OCT images of skin with thin
      and thick epidermis and the morphological structure was confirmed. OCT images of
      healthy skin comprise three layers in case of skin with thin epidermis and four
      layers in skin with thick epidermis. The OCT image of the zone of the transition
      from skin with thick to skin with thin epidermis features five layers.
      CONCLUSION: The revealed differences in the structure of horny and cellular
      layers of epidermis, as well as of papillary and reticular dermis in skin with
      thin and thick epidermis specify different optical properties of these layers in
      OCT images.

PMID- 25594489
TI  - Establishment of the Prediction Equations of 1RM Skeletal Muscle Strength in 60-
      to 75-Year-Old Chinese Men and Women.
AB  - The purpose of this study was to establish the one-repetition maximum (1RM)
      prediction equations of a biceps curl, bench press, and squat from the submaximal
      skeletal muscle strength of 4-10RM or 11-15RM in older adults. The first group of
      109 participants aged 60-75 years was recruited to measure their 1RM, 4-10RM, and
      11-15RM of the three exercises. The 1RM prediction equations were developed by
      multiple regression analyses. A second group of participants with similar
      physical characteristics to the first group was used to evaluate the equations.
      The actual measured 1RM of the second group correlated significantly to the
      predicted 1RM obtained from the equations (r values were from .633-.985), and
      standard error of estimate ranged from 1.08-5.88. Therefore, the equations can be
      used to predict 1RM from submaximal skeletal muscle strength accurately for older
      adults. 

PMID- 25594490
TI  - Homoleptic tetranuclear rhodium carbonyls: comparison with their iridium
      analogues.
AB  - Density functional theory confirms the experimentally known triply bridged
      Rh4(CO)9(MU-CO)3 structure to be the lowest-energy structure. The lowest-energy
      structures of the unsaturated systems Rh4(CO)n (n = 11, 10, 9, 8) are also triply
      bridged structures with central Rh4 tetrahedra that can be derived from this
      Rh4(CO)9(MU-CO)3 structure by removal of terminal CO groups in various ways. The
      M-M distances in these central M4 tetrahedra change very little as CO groups are
      lost, suggesting reluctance to form metal-metal multiple bonds in these
      unsaturated systems. The natural bond orbital (NBO) Wiberg bond indices provide
      depth to this analysis. All of these unsaturated systems are predicted to be
      highly fluxional, as two to three isomeric structures lie within ~4 kcal/mol of
      the global minima. The Rh4(CO)8(MU-CO)2(MU4-CO) structure analogous to the lowest
      energy Co4(CO)11 structure with all four atoms of a central Co4 butterfly bridged
      by a MU-CO group is predicted to lie ~6 kcal/mol in energy above the lowest
      energy Rh4(CO)11 structure. Comparisons of the relative energies of analogous
      Rh4(CO)n and Ir4(CO)n structures indicate that more highly bridged M4(CO)n
      structures are energetically much more favorable for rhodium than for iridium.
      Dissociation energies (for loss of CO) and disproportionation energies are
      reported. 

PMID- 25594491
TI  - Synchrotron-FTIR microspectroscopy enables the distinction of lipid accumulation
      in thraustochytrid strains through analysis of individual live cells.
AB  - The superior characteristics of high photon flux and diffraction-limited spatial
      resolution achieved by synchrotron-FTIR microspectroscopy allowed molecular
      characterization of individual live thraustochytrids. Principal component
      analysis revealed distinct separation of the single live cell spectra into their
      corresponding strains, comprised of new Australasian thraustochytrids (AMCQS5-5
      and S7) and standard cultures (AH-2 and S31). Unsupervised hierarchical cluster
      analysis (UHCA) indicated close similarities between S7 and AH-7 strains, with
      AMCQS5-5 being distinctly different. UHCA correlation conformed well to the fatty
      acid profiles, indicating the type of fatty acids as a critical factor in
      chemotaxonomic discrimination of these thraustochytrids and also revealing the
      distinctively high polyunsaturated fatty acid content as key identity of AMCQS5
      5. Partial least squares discriminant analysis using cross-validation approach
      between two replicate datasets was demonstrated to be a powerful classification
      method leading to models of high robustness and 100% predictive accuracy for
      strain identification. The results emphasized the exceptional S-FTIR capability
      to perform real-time in vivo measurement of single live cells directly within
      their original medium, providing unique information on cell variability among the
      population of each isolate and evidence of spontaneous lipid peroxidation that
      could lead to deeper understanding of lipid production and oxidation in
      thraustochytrids for single-cell oil development. 

PMID- 25594492
TI  - Morphological and molecular diversification of Asian endemic Difflugia
      tuberspinifera (Amoebozoa, Arcellinida): a case of fast morphological evolution
      in protists?
AB  - Planktonic arcellinid testate amoebae exhibit a broad-range of morphological
      variability but it is currently unclear to what extent this variability
      represents phenotypic plasticity or if it is genetically determined. We
      investigated the morphology and phylogenetic relationships of three endemic east
      asian Difflugia taxa 1) the vase-shaped D. mulanensis, 2) and a spinose and a
      spineless morphotypes of D. tuberspinifera using scanning electron microscopy and
      two ribosomal genetic markers (SSU rDNA and ITS sequences). Our phylogenetic
      analyses shows that all three taxa are genetically distinct and closely related
      to D. achlora and Netzelia oviformis. The genetic variations between the
      spineless and spinose morphotypes of D. tuberspinifera were low at the SSU rRNA
      level (0.4%), but ten times higher at the ITS level (4.5-6%). Our data suggest
      that the two forms of D. tuberspinifera are sufficiently differentiated in terms
      of morphology and genetic characteristics to constitute two separate entities and
      that the presence of spines does not result from phenotypic plasticity due to
      environmental selective pressure. However further observational and experimental
      data are needed to determine if these two forms constitute different biological
      species. 

PMID- 25594494
TI  - Conductance measurements of individual polypyrrole nanobelts.
AB  - We present here a study on the electrical conduction properties of individual
      polypyrrole nanobelts by using conductive atomic force microscopy and discuss a
      general effect while probing soft materials. A length-dependent analysis
      demonstrates that the tip could induce local defects into the polymer structure
      and, thus diminishes the electrical conduction. 

PMID- 25594493
TI  - Effect of heavy metals on fish larvae deformities: A review.
AB  - Heavy metals have been associated with many fish deformities in natural
      populations and in laboratory produced specimens as well. Deformities in general
      have devastating effects on fish populations since they affect the survival, the
      growth rates, the welfare and their external image. Although the embryonic stage
      in respect to heavy metal exposure has been extensively studied, there is not
      much information available as to what happens in fish larvae and adults. In the
      present article, we present the available information on the effect of heavy
      metals on fish larvae deformities. We also address the need for more research
      towards the effects of metals on the subsequent life stages in order to assess
      the long-term consequences of heavy metal poisoning on fish organisms and
      possibly correlate these consequences with the environmental contamination (use
      as biomarkers). 

PMID- 25594495
TI  - Venous thromboembolism prophylaxis in critically ill patients.
AB  - Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary
      embolism (PE), is recognized as a common complication in critically ill patients.
      Risk factors including critical illness, mechanical ventilation, sedative
      medications, and central venous catheter insertion are major contributing factors
      to the high risk of VTE. Because of their impaired cardiopulmonary reserve, PE
      arising from thrombosis in the deep veins of the calf that propagates proximally
      is poorly tolerated by critically ill patients. Pharmacologic prophylaxis with
      unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) has been
      shown to decrease the incidence of VTE in medical, surgical, and critically ill
      patients. As a result, over the past decades, VTE prophylaxis had become a
      standard of preventive measure in the intensive care unit (ICU). In clinical
      practice, the rate of VTE prophylaxis varies and may be inadequate in some
      centers. A perception of a high bleeding risk in critically ill patients is a
      major concern for most physicians that may lead to inadequate prophylaxis. 

PMID- 25594496
TI  - Efficacy of argatroban in critically ill patients with heparin resistance: a
      retrospective analysis.
AB  - The patients who do not respond even to very high dosages of heparin are assumed
      to suffer from heparin resistance. The aim of this study was to investigate
      whether critically ill patients suffering from heparin resistance generally have
      low antithrombin III (AT) levels, and if the direct thrombin inhibitor argatroban
      in that case can be an effective option to achieve prophylactic anticoagulation.
      The study was conducted at the Department for General and Surgical Intensive Care
      Medicine at the University Hospital Innsbruck. We retrospectively included all
      patients between 2008 and 2012, who received argatroban because of poor response
      to high-dosage heparin prophylaxis. The period under observation lasted in total
      for 9 days, 2 days of anticoagulation with unfractionated heparin (UFH) and 7
      days with argatroban. The primary objective was to investigate if after 7 (+/- 1)
      hours of switching to argatroban the activated partial thromboplastin time (aPTT)
      levels were in a prophylactic range of 45 to 55 seconds. Further objectives were
      to assess the AT level, side effects such as bleeding or thromboembolism,
      platelet count, correlation between organ function and argatroban dose as well as
      any need for allogeneic blood products. The study population, consisting of 5
      women and 15 men with a mean (+/- standard deviation, SD) age of 54.6 +/- 16.3
      years, differed in many clinical aspects. A median (interquartile range) heparin
      dose of 1,000, 819 to 1,125 IU/h was administered for 2 days and failed in
      providing a prophylactic anticoagulation measured by the aPTT. The mean aPTT
      level with heparin treatment was 38.5 seconds (+/- 4.7) its change within that
      period was not significant. After switching to argatroban, the mean increase of
      the aPTT levels in all study patients amounted from 38.5 to 48.3 seconds (p <
      0.001). The rise in aPTT clearly reaches sufficient prophylactic anticoagulant
      levels. The maintenance of prophylactic aPTT levels was achieved over the period
      of 1 week. There was neither a correlation found between low-AT levels and
      occurrence of heparin resistance, nor between the simplified acute physiology
      score II and the administered argatroban dose (r = -0.224, p = 0.342). The
      results of the present study indicate that argatroban is an effective alternative
      therapy, especially in critically ill patients, to achieve prophylactic
      anticoagulation when heparin resistance occurs. 

PMID- 25594497
TI  - Molecular dynamics simulation and free energy calculation studies of kinase
      inhibitors binding to active and inactive conformations of VEGFR-2.
AB  - Vascular endothelial growth factors receptor-2 (VEGFR-2) inhibitors have been
      proved as very effective anticancer agents. Structurally similar ligands 1 and 2
      show almost the same inhibitory activities against VEGFR-2, but they bind to the
      enzyme in distinct binding mode. Ligand 1 targets DFG-in active conformation of
      VEGFR-2, known as Type I inhibitor. On the other hand, ligand 2 targets DFG-out
      inactive conformation of VEGFR-2, known as Type II inhibitor or allosteric kinase
      inhibitor. Ligand 2 shows high inhibitory activity, while the compound 3, a close
      analog of 2 with the cyclopropylamide replaced by tert-butylamide, exhibits
      drastically diminished potency. In this work, molecular dynamics simulations and
      free energy calculations were performed on inhibitors 1-3 binding to active and
      inactive conformation of VEGFR-2. Molecular dynamics simulations find that the
      active conformation binding to Type I inhibitor 1 appears more flexible when
      compared to the unbound form. In contrast, binding of Type II inhibitor 2 to the
      inactive conformation helps to stabilize the inactive conformation of the
      protein. Binding free energy calculations verify that inhibitors 1 and 2 have
      almost the same activities against VEGFR-2, and that ligand 1 binds to and
      stabilizes the DFG-in conformation of VEGFR-2, which is in agree with the
      experimental observation. Molecular dynamics simulations and binding free energy
      calculations of 3 binding to VEGFR-2 can give a good explanation of the
      drastically diminished potency. Free energy analysis revealed that van der Waals
      interactions provided the substantial driving force for the binding process. The
      important hydrophobic property of the terminal 4-Cl phenyl was required to be
      Type II inhibitors. Furthermore, per-residue free energy decomposition analysis
      revealed that the most favorable contribution came from Leu840, Val848, Ala866,
      Lys868, Leu889, Val899, Thr916, Phe918, Cys919, Leu1035, Cys1045, Asp1046, and
      Phe1047. These results are expected to be useful for future rational design of
      novel potent VEGFR-2 inhibitors. 

PMID- 25594498
TI  - Adult digit ratio (2D:4D) is not related to umbilical cord androgen or estrogen
      concentrations, their ratios or net bioactivity.
AB  - BACKGROUND: Ratio of second digit length to fourth digit length (2D:4D) has been
      extensively used in human and experimental research as a marker of fetal sex
      steroid exposure. However, very few human studies have measured the direct
      relationship between fetal androgen or estrogen concentrations and digit ratio.
      AIMS: We investigated the relationships between both androgen and estrogen
      concentrations in umbilical cord blood and digit ratio in young adulthood. In
      addition we calculated measures of total serum androgen and total estrogen
      bioactivity and investigated their relationship to digit ratio. STUDY DESIGN:
      Prospective cohort study. SUBJECTS: An unselected subset of the Western
      Australian Pregnancy Cohort (Raine) Study (159 female; 182 male). OUTCOME
      MEASURES: Cord serum samples were collected immediately after delivery. Samples
      were assayed for androgen (testosterone, Delta4-androstenedione,
      dehydroepiandrosterone) and estrogen (estrone, estradiol, estriol, estetrol)
      concentrations using liquid-chromatography mass-spectrometry. Digit ratio
      measurements were taken from hand photocopies at age 19-22years. RESULTS: For
      both males and females, there were no significant correlations between digit
      ratio and any androgen or estrogen concentrations considered individually, the
      testosterone to estradiol ratio, total androgen bioactivity measure or ratio of
      androgen to estrogen bioactivity (all p>.05). In males, but not females, total
      estrogen bioactivity was negatively correlated with left hand digit ratio (r=
      .172, p=.02), but this relationship was no longer significant when adjusted for
      variables known to affect sex steroid concentrations in cord blood. CONCLUSIONS:
      Our findings indicate that digit ratio is not related to fetal androgens or
      estrogens at late gestation.

PMID- 25594500
TI  - Sharing clinical trial data: maximizing benefits, minimizing risk.

PMID- 25594499
TI  - Antioxidative status and oxidative stress in the fetal circulation at birth: the
      effects of time of delivery and presence of labor.
AB  - BACKGROUND: There are important physiological changes in the maternal, placental,
      and fetal compartments during pregnancy and labor. Increased oxidative stress has
      been demonstrated during labor. Melatonin has been reported to serve as an
      indirect antioxidant via the stimulation and induction of antioxidant enzymes as
      superoxide dismutase (SOD) and glutathione peroxidase (Gpx) in several tissues.
      AIM: : To assess whether the melatonin status, presence of labor at the time of
      birth and the time of delivery influence the extracellular antioxidative enzymes
      and DNA oxidative stress in newborns. METHODS: The extracellular antioxidative
      status and oxidative stress were analyzed by measuring the concentrations of the
      SOD3, Gpx3 and 8-hydroxydeoxyguanosine (8-OHdG) in the cord blood of 135
      newborns. Newborns delivered during the day and at night and newborns delivered
      by spontaneous vaginal delivery (labor group) or elective caesarean section
      delivery (no labor group) were studied. OUTCOME MEASURES: The concentration of
      melatonin, SOD3, Gpx3 and 8-OHdG. RESULTS: Independent of the time of delivery,
      we found significantly higher melatonin, SOD3 and Gpx3 but lower 8-OHdG
      concentrations in the labor group than in the no labor group. We did not observe
      a correlation between the concentration of melatonin and SOD3, Gpx3 or 8-OHdG, or
      a day-night difference in SOD3, Gpx3 or 8-OHdG. CONCLUSION: Our findings suggest
      that oxidative stress during labor leads to an elevation of melatonin, SOD3 and
      Gpx3 in the fetal circulation, protecting the newborn from serious impairment,
      which is reflected by lower 8-OHdG levels. The melatonin status at the time of
      birth does not influence the extracellular SOD3 or Gpx3 concentrations.

PMID- 25594501
TI  - A comparison of assays for accurate copy number measurement of the low-affinity
      Fc gamma receptor genes FCGR3A and FCGR3B.
AB  - The FCGR3 locus encoding the low affinity activating receptor FcgammaRIII, plays
      a vital role in immunity triggered by cellular effector and regulatory functions.
      Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect
      susceptibility to several autoimmune diseases and chronic inflammatory
      conditions. However, such genetic association studies often yield inconsistent
      results; hence require assays that are robust with low error rate. We
      investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing
      Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant
      ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B
      CNV were carried out using real-time quantitative PCR, we have also included the
      evaluation of that method's performance in estimating the multi-allelic CNV of
      FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal
      intensity, potentially introducing error in estimation of copy number and higher
      false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias,
      but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between
      Sequenom and PRT-REDVR might be attributed either to batch effects noise in
      individual measurements. Our study suggests that PRT-REDVR is more robust and
      accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple
      independent assays for extensive validation when performing a genetic association
      study with multi-allelic CNVs. 

PMID- 25594503
TI  - COQ2 gene variants associate with cerebellar subtype of multiple system atrophy
      in Chinese.

PMID- 25594504
TI  - A reversible decrease in ribulose 1,5-bisphosphate carboxylase/oxygenase
      carboxylation activity caused by the aggregation of the enzyme's large subunit is
      triggered in response to the exposure of moderate irradiance-grown plants to low
      irradiance.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is highly regulated in
      response to fluctuations in the environment, including changes in irradiance.
      However, no complex data are available on Rubisco regulatory mechanisms triggered
      in plants which are submitted to moderate-low irradiance shift. Therefore, we
      investigated in a comprehensive way the changes at the level of amount of Rubisco
      protein, its structural organization and carboxylase activity of the holoenzyme
      as triggered by exposure of moderate irradiance-grown Arabidopsis thaliana plants
      to low irradiance conditions. An exposure of moderate irradiance-grown plants to
      low irradiance for a single photoperiod caused the exclusion of a certain pool of
      Rubisco under altered conditions owing to oxidative modifications resulting in
      the formation of protein aggregates involving Rubisco large subunit (LS). As a
      result, both initial and total Rubisco carboxylase activities were reduced,
      whereas Rubisco activation state remained largely unchanged. The results of the
      determination of reactive oxygen species indicated that a moderate/low irradiance
      transition had stimulated (1) O2 accumulation and we strongly suggest that
      Rubisco oxidative modifications leading to formation of aggregates encompassing
      Rubisco-LS were triggered by (1) O2 . When moderate irradiance regime was
      resumed, the majority of Rubisco-LS containing aggregates tended to be
      resolubilized, and this allowed Rubisco carboxylation activities to be largely
      recovered, without changes in the activation state of the enzyme. In the longer
      term, these results allow us to better understand a complexity of Rubisco
      regulatory mechanisms activated in response to abiotic stresses and during
      recovery from the stresses. 

PMID- 25594505
TI  - Thermophilic biofilter for SO2 removal: performance and microbial
      characteristics.
AB  - A bench-scale thermophilic biofilter was applied to remove SO2 at 60 degrees C in
      the present study. The SO2 concentration in the inlet stream ranged from
      100mg/m(3) to 200mg/m(3). An average SO2 removal efficiency of 93.10% was
      achieved after developing acclimated organisms that can degrade SO2. The
      thermophilic biofilter effectively reduced SO2, with a maximum elimination
      capacity of 50.67g/m(3)/h at a loading rate of 51.44g/m(3)/h. Removal efficiency
      of the thermophilic biofilter was largely influenced by the water containing rate
      of the packing materials. The SO2 transfer in the biofilter included adsorption
      by the packing materials, dissolution in liquid, and microbial degradation. The
      main product of SO2 degradation was SO4(2-). The temporal shifts in the bacterial
      community that formed in the biofilter were determined through polymerase chain
      reaction-denaturing gradient gel electrophoresis and DNA sequence analysis. These
      shifts revealed a correlation between biofilter performance and bacterial
      community structure. 

PMID- 25594506
TI  - Rapid mineralisation of the Organic Fraction of Municipal Solid Waste.
AB  - The effect of pH, C/N ratio, addition of a microbial consortium (MC) and
      temperature upon mineralisation of Organic Fraction of Municipal Solid Waste
      (OFMSW) was studied; mineralisation was measured through the CO2 production rate
      and total CO2 formation. Through this process up to 432.9mg of CO2g(-1) initial
      dry matter (IDM) after 2days of treatment was obtained. It was found that under a
      slightly acidic pH (5-6) and C/N of 30, the mineralisation process was
      accelerated. Moreover, temperature (27-50 degrees C) had no effect on the total
      CO2 produced. The highest CO2 production rate (5.28d(-1)) was observed at 27
      degrees C, C/N ratio of 30 and 8% of microbial consortium; it is at least 3.52
      times higher than that reported (1.5d(-1)). The highest release of reducing
      sugars was determined at 50 degrees C, possibly due to an increase in hydrolytic
      enzymes. Results suggest the potential use of rapid mineralisation of OFMSW for
      further friendly environmental processes. 

PMID- 25594507
TI  - A metabolic-based approach to improve xylose utilization for fumaric acid
      production from acid pretreated wheat bran by Rhizopus oryzae.
AB  - In this work, wheat bran (WB) was utilized as feedstock to synthesize fumaric
      acid by Rhizopus oryzae. Firstly, the pretreatment process of WB by dilute
      sulfuric acid hydrolysis undertaken at 100 degrees C for 30min offered the best
      performance for fumaric acid production. Subsequently, through optimizing the
      seed culture medium, a suitable morphology (0.55mm pellets diameter) of R. oryzae
      was obtained. Furthermore, a metabolic-based approach was developed to profile
      the differences of intracellular metabolites concentration of R. oryzae between
      xylose (the abundant sugar in wheat bran hydrolysate (WBH)) and glucose
      metabolism. The xylitol, sedoheptulose 7-phosphate, ribulose 5-phosphate, glucose
      6-phosphate, proline and serine were responsible for fumaric acid biosynthesis
      limitation in xylose fermentation. Consequently, regulation strategies were
      proposed, leading to a 149% increase in titer (up to 15.4g/L). Finally, by
      combinatorial regulation strategies the highest production was 20.2g/L from WBH,
      477% higher than that of initial medium. 

PMID- 25594508
TI  - High temperature simultaneous saccharification and fermentation of starch from
      inedible wild cassava (Manihot glaziovii) to bioethanol using Caloramator
      boliviensis.
AB  - The thermoanaerobe, Caloramator boliviensis was used to ferment starch
      hydrolysate from inedible wild cassava to ethanol at 60 degrees C. A raw starch
      degrading alpha-amylase was used to hydrolyse the cassava starch. During
      fermentation, the organism released CO2 and H2 gases, and Gas Endeavour System
      was successfully used for monitoring and recording formation of these gaseous
      products. The bioethanol produced in stoichiometric amounts to CO2 was registered
      online in Gas Endeavour software and correlated strongly (R(2)=0.99) with values
      measured by HPLC. The organism was sensitive to cyanide that exists in cassava
      flour. However, after acclimatisation, it was able to grow and ferment cassava
      starch hydrolysate containing up to 0.2ppm cyanide. The reactor hydrogen partial
      pressure had influence on the bioethanol production. In fed-batch fermentation by
      maintaining the hydrogen partial pressure around 590Pa, the organism was able to
      ferment up to 76g/L glucose and produced 33g/L ethanol. 

PMID- 25594509
TI  - The chemistry and biological activities of peptides from amphibian skin
      secretions.

PMID- 25594510
TI  - Therapeutic effect of ghrelin in the course of ischemia/reperfusion-induced acute
      pancreatitis.
AB  - BACKGROUND: Protective effect of pretreatment with ghrelin against different
      forms of acute pancreatitis (AP) has been recently reported. Moreover, the
      healing properties of this peptide have been proved in AP evoked by cerulein.
      However, no studies have investigated whether the administration of ghrelin
      affects the course of ischemia/reperfusion-induced AP. AIM: The aim of this study
      was to evaluate the impact of ghrelin therapy on the course of necrotizing
      inflammation of the pancreas and to test its impact on peroxidation of lipids and
      antioxidant defense system in the acutely inflamed pancreas. METHODS: Acute
      inflammation of the pancreas was triggered by pancreatic ischemia which was then
      followed by reperfusion of the gland. Ghrelin (8 nmol/kg/dose) was administered
      to intraperitoneally twice daily, 24h after the initiation of AP. The impact of
      ghrelin on the course of necrotizing pancreatitis was evaluated between 1 and 21
      days, and involved histological, functional, and biochemical analyses. RESULTS:
      Treatment with ghrelin ameliorated morphological signs of pancreatic damage
      including edema, acinar cells vacuolization, hemorrhages, acinar necrosis,
      leukocytic infiltration of the gland, and led to its earlier regeneration. These
      effects were accompanied by an improvement in pancreatic blood flow, enhanced DNA
      synthesis, reduced serum level of pro- inflammatory interleukin-1beta, decreased
      levels of malondialdehyde and an enhanced superoxide dismutase activity in
      pancreatic tissue. CONCLUSIONS: Ghrelin exerts a pronounced therapeutic effect
      against ischemia-reperfusion-induced pancreatitis. The mechanisms involved are
      likely multifactorial and are mediated by its anti-inflammatory, as well as anti
      oxidative properties.

PMID- 25594511
TI  - Cell--cell crosslinking by bio-molecular recognition of heparin-based layer-by
      layer nanofilms.
AB  - When bio-molecular recognition between nanofilms and proteins occurs on cell
      surfaces, rapid cellular assembly takes place. Cells coated with layer-by-layer
      nanofilms composed of fibronectin and heparin form aggregates after
      centrifugation and nanofilms induce attractive forces between cells through bio
      molecular recognition between membrane proteins and heparin. Cell aggregates
      display network structures of cells as seen in colloidal gels with high
      viscosity. Cell-cell crosslinking allows for the construction of 3D-tissues with
      rich glycosaminoglycan. This cell-cell crosslinking process that uses a layer-by
      layer technique has enormous potential for in vitro tissue applications in
      regenerative medicine and cell signaling assays. 

PMID- 25594512
TI  - The association between social relationships and depression: a systematic review.
AB  - BACKGROUND: Depression is one of the most prevalent mental disorders globally and
      has implications for various aspects of everyday-life. To date, studies assessing
      the association between social relationships and depression have provided
      conflicting results. The aim of this paper was to review the evidence on
      associations between social relationships and depression in the general
      population. METHODS: Studies investigating the association of social support,
      social networks, or social connectedness with depression were retrieved and
      summarized (searches using Pubmed, ScienceDirect, PsycNet were conducted in May
      2014). RESULTS: Fifty-one studies were included in this review. The strongest and
      most consistent findings were significant protective effects of perceived
      emotional support, perceived instrumental support, and large, diverse social
      networks. Little evidence was found on whether social connectedness is related to
      depression, as was also the case for negative interactions. LIMITATIONS: Due to
      the strict inclusion criteria relating to study quality and the availability of
      papers in the domain of interest, the review did not capture 'gray literature'
      and qualitative studies. CONCLUSION: Future research is warranted to account for
      potential bias introduced by the use of subjective measures as compared to
      objective measures of received support and actual networks. Due to the
      heterogeneity between available studies on the measure of social relationships,
      the inclusion of comparable measures across studies would allow for more valid
      comparisons. In addition, well-designed prospective studies will provide more
      insight into causality. Future research should address how social support and
      networks interact and together affect risks for depression. Social connectedness
      and negative interactions appear to be underutilized as measures in population
      based studies.

PMID- 25594514
TI  - Anchoring groups for dye-sensitized solar cells.
AB  - The dyes in dye-sensitized solar cells (DSSCs) require one or more chemical
      substituents that can act as an anchor, enabling their adsorption onto a metal
      oxide substrate. This adsorption provides a means for electron injection, which
      is the process that initiates the electrical circuit in a DSSC. Understanding the
      structure of various DSSC anchors and the search for new anchors are critical
      factors for the development of improved DSSCs. Traditionally, carboxylic acid and
      cyanoacrylic acid groups are employed as dye anchors in DSSCs. In recent years,
      novel anchor groups have emerged, which make a larger pool of materials available
      for DSSC dyes, and their associated physical and chemical characteristics offer
      interesting effects at the interface between dye and metal oxide. This review
      focuses especially on the structural aspects of these novel dye anchors for TiO2
      based DSSCs, including pyridine, phosphonic acid, tetracyanate, perylene
      dicarboxylic acid anhydride, 2-hydroxylbenzonitrile, 8-hydroxylquinoline,
      pyridine-N-oxide, hydroxylpyridium, catechol, hydroxamate, sulfonic acid,
      acetylacetanate, boronic acid, nitro, tetrazole, rhodanine, and salicylic acid
      substituents. We anticipate that further exploration and understanding of these
      new types of anchoring groups for TiO2 substrates will not only contribute to the
      development of advanced DSSCs, but also of quantum dot-sensitized solar cells,
      water splitting systems, and other self-assembled monolayer-based technologies. 

PMID- 25594515
TI  - Nanosensor composed of nitrogen-doped carbon dots and gold nanoparticles for
      highly selective detection of cysteine with multiple signals.
AB  - Biological thiols play a critical role in biological processes and are involved
      in a variety of diseases. The discrimination detection of biological thiols is of
      increasing importance in clinical diagnosis. In this paper, a novel nanosensor
      was developed to discriminate cysteine (Cys) from homocysteine (Hcy) and
      glutathione (GSH) with multiple signals: colorimetric, photoluminescence (PL),
      and up-conversional photoluminescence (UCP). The nanosensor (NC-dots/AuNPs) was
      constructed by nitrogen-doped carbon dots (NC-dots) and gold nanoparticles
      (AuNPs) through assembling NC-dots "shell" on AuNPs and showed the obvious
      different response to Cys, Hcy, and GSH with colorimetric, PL, and UCP signals.
      The discrimination effect for Cys is originated from conformations and
      interaction difference of the thiols groups in Cys and Hcy and/or GSH with AuNPs.
      Among them, only Cys can quickly penetrate into the NC-dots "shell" of the
      composite and induce the dispersing of the aggregated NC-dots/AuNPs, which lead
      to the color change from purple to red and the recovery of PL and UCP of NC-dots.
      This assay was successfully applied for the detection of Cys in human serum with
      the detection limit of 4 nM. 

PMID- 25594513
TI  - Interventions to prevent repeat suicidal behavior in patients admitted to an
      emergency department for a suicide attempt: a meta-analysis.
AB  - BACKGROUND: A huge number of patients with self-harm and suicide attempt visit
      emergency departments (EDs). We systematically reviewed studies and examined the
      effect of interventions to prevent repeat suicidal behavior in patients admitted
      to EDs for a suicidal attempt. METHOD: We searched the databases of MEDLINE,
      PsychoINFO, CINAHL, and EMBASE through August 2013. Eligible studies were
      randomized controlled trials assessing the effects on repeat suicidal behavior of
      interventions initiated in suicidal patients admitted to EDs. Interventions in
      each trial were classified into groups by consensus. Meta-analyses were performed
      to determine pooled relative risks (RRs) and 95% confidence intervals (CIs) of
      repetition of suicide attempt for interventions in each group. RESULTS: Out of
      5390 retrieved articles, 24 trials were included and classified into four groups
      (11 trials in the Active contact and follow-up, nine in the Psychotherapy, one in
      the Pharmacotherapy, and three in the Miscellaneous). Active contact and follow
      up type interventions were effective in preventing a repeat suicide within 12
      months (n=5319; pooled RR=0.83; 95% CI: 0.71 to 0.97). However, the effect at 24
      months was not confirmed (n=925; pooled RR=0.98; 95% CI: 0.76-1.22). The effects
      of the other interventions on preventing a repetition of suicidal behavior remain
      unclear. LIMITATION: Caution is needed regarding the heterogeneity of the
      effects. CONCLUSION: Interventions of active contact and follow-up are
      recommended to reduce the risk of a repeat suicide attempt at 12 months in
      patients admitted to EDs with a suicide attempt. However, the long-term effect
      was not confirmed.

PMID- 25594516
TI  - Patterns in benthic biodiversity link lake trophic status to structure and
      potential function of three large, deep lakes.
AB  - Relative to their scarcity, large, deep lakes support a large proportion of the
      world's freshwater species. This biodiversity is threatened by human development
      and is in need of conservation. Direct comparison of biodiversity is the basis of
      biological monitoring for conservation but is difficult to conduct between large,
      insular ecosystems. The objective of our study was to conduct such a comparison
      of benthic biodiversity between three of the world's largest lakes: Lake Tahoe,
      USA; Lake Hovsgol, Mongolia; and Crater Lake, USA. We examined biodiversity of
      common benthic organism, the non-biting midges (Chironomidae) and determined lake
      trophic status using chironomid-based lake typology, tested whether community
      structure was similar between the three lakes despite geographic distance; and
      tested whether chironomid diversity would show significant variation within and
      between lakes. Typology analysis indicated that Lake Hovsgol was ultra
      oligotrophic, Crater Lake was oligotrophic, and Lake Tahoe was borderline
      oligotrophic/mesotrophic. These results were similar to traditional pelagic
      measures of lake trophic status for Lake Hovsgol and Crater Lake but differed for
      Lake Tahoe, which has been designated as ultra-oligotrophic by traditional
      pelagic measures such as transparency found in the literature. Analysis of
      similarity showed that Lake Tahoe and Lake Hovsgol chironomid communities were
      more similar to each other than either was to Crater Lake communities. Diversity
      varied between the three lakes and spatially within each lake. This research
      shows that chironomid communities from these large lakes were sensitive to
      trophic conditions. Chironomid communities were similar between the deep
      environments of Lake Hovsgol and Lake Tahoe, indicating that chironomid
      communities from these lakes may be useful in comparing trophic state changes in
      large lakes. Spatial variation in Lake Tahoe's diversity is indicative of
      differential response of chironomid communities to nutrient enrichment which may
      be an indication of changes in trophic state within and across habitats. 

PMID- 25594517
TI  - Examination of muscle strength and pressure pain thresholds in knee
      osteoarthritis: test-retest reliability and agreement.
AB  - BACKGROUND AND PURPOSE: Knee osteoarthritis (OA) is associated with reduced
      muscle strength and pain sensitization. The purpose of this study was to
      determine intrarater reliability and agreement (measurement error) of isometric
      knee extensor and flexor muscle strength assessed using handheld dynamometry and
      of pressure pain thresholds (PPT; a measure of pain sensitization) from the knee,
      the leg, and the forearm assessed using handheld algometry in knee OA. METHODS: A
      total of 20 subjects with knee OA participated in 2 sessions separated by 1 week.
      The highest of 4 examinations and the mean of the 3 highest examinations of
      muscle strength and the first and the mean of 2 PPT examinations were applied in
      the statistical analyses. Intrarater reliability was assessed using a 2-way
      random-effects model, consistency-type intraclass correlation coefficient,
      whereas agreement was assessed using 95% limits of agreement (LOA) as a
      percentage of the mean (LOA%). RESULTS: Intraclass correlation coefficients for
      muscle strength were between 0.78 and 0.91 when using the highest examination and
      were between 0.86 and 0.94 when using the mean of the 3 highest examinations.
      Intraclass correlation coefficients for PPT were between 0.53 and 0.87 when using
      the first examination and were between 0.84 and 0.91 when using the mean of 2
      examinations. Agreement (LOA%) for muscle strength ranged from 38.3% to 47.3%
      when using the highest examination and from 40.4% to 53.3% when using the mean of
      the 3 highest examinations. Agreement for PPT ranged from 54.2% to 80.6% when
      using the first examination and from 50.6% to 58.9% when using the mean of 2 PPT
      examinations. DISCUSSION: A tendency toward improved intraclass correlation
      coefficients and LOA% (only for PPTs) was found when using the mean of more than
      1 examination for both muscle strength and PPTs. Intrarater reliability was high
      to very high, whereas the LOA/LOA% indicated relatively high measurement errors.
      CONCLUSIONS: Examination of muscle strength and PPTs in knee OA is reliable, but
      affected by the measurement error, which is important to consider when reporting
      the results of clinical trials and in clinical practice.

PMID- 25594518
TI  - Factors Associated With Muscle Strength Among Rural Community-Dwelling Older
      Women in Southern Brazil.
AB  - BACKGROUND AND PURPOSE: Muscle strength is an important predictor of disability,
      mortality, and health complications among older adults. The objective of this
      study was to verify the sociodemographic factors, lifestyle, and health
      conditions associated with inadequate muscle strength in older women in a rural
      community in the South of Brazil. METHODS: This was a cross sectional study
      employing a probabilistic sample (2010-2011) of 270 older adult women (>= 60
      years). Handgrip strength (HGS) was measured with a dynamometer (Takei, Japan).
      Lower limb muscle strength (LLMS) was assessed through the "chair stand test."
      The variables analyzed were age, literacy, current work status, living
      arrangement, occupation throughout life, smoking, sitting time, number of
      morbidities, history of falls, and cognitive function. The prevalence ratio was
      used as a measure of association, by Poisson regression analysis (crude and
      adjusted). RESULTS: The mean age of the older women was 73.2 (standard deviation,
      8.8) years. The proportion of women who presented with inadequate HGS and LLMS
      was 18.8% (95% confidence interval, 13.8-23.7) and 29.8% (95% confidence
      interval, 23.9-35.6), respectively. Inadequate strength in the 2 tests was
      associated with age, the condition of not working, and altered cognitive
      function. Inadequate strength in the LLMS test was associated with having fallen
      during the last year. CONCLUSIONS: Factors associated with muscle strength are
      specific to the test. The following sociodemographic and health variables were
      positively associated with inadequate strength on the HGS and LLMS tests:
      advancing age, not working, and altered cognitive function. A history of falls is
      associated with inadequate performance on the LLMS test.

PMID- 25594519
TI  - Effect of a dual-task net-step exercise on cognitive and gait function in older
      adults.
AB  - BACKGROUND AND PURPOSE: Participation in generally recommended aerobics or
      strength exercises may be challenging for older adults. Therefore, it is
      necessary to consider the types and levels of physical activities suited for them
      to improve their cognitive and gait function and adherence to exercise programs.
      This has prompted efforts to identify exercises that require less physical
      strength and frequency of performance, while still offering cognitive and health
      benefits. Here, we aimed to assess the effect of a novel dual-task net-step
      exercise (NSE) performed once a week for 8 consecutive weeks on improvements in
      cognitive performance and gait function in an older population. METHODS: In this
      pretest/posttest experimental case control study, 60 healthy older adults (mean
      age 76.4 years) were recruited from community-dwelling people and separated
      randomly into 2 groups: a dual-task NSE group and a control group. The NSE group
      was asked to walk across a net without stepping on the ropes or being caught in
      the net. Two computer panel-type cognitive functional assessments, the Touch-M
      and Touch Panel-Type Dementia Assessment Scale, were administered at baseline and
      after 8 weeks of intervention to determine the effects of NSE. Improvements in
      gait function were also evaluated using Timed Up and Go test scores. Mixed-effect
      models with repeated measures (group * time) (analysis of variance, F test) were
      used to test the effects of NSE. Adjustments were made for covariates including
      age and sex (analysis of covariance). RESULTS: The NSE group showed significant
      improvement in cognitive performance (6.8% change; total Touch-M score 5.4
      points; P = .04) and gait performance (11.5% change; Timed Up and Go time -0.98
      second; P < .001) over the 8-week period. In the control group, there was no
      significant improvement. CONCLUSIONS: This study shows that dual-task NSE is
      capable of improving cognitive and gait performance in healthy older adults. Our
      results indicate that NSE offers an option for a large segment of the older
      population who need an easier way to maintain their cognitive health and gait
      function.

PMID- 25594520
TI  - Understanding the relationship between walking aids and falls in older adults: a
      prospective cohort study.
AB  - BACKGROUND: A substantial proportion of older adults living in residential aged
      care facilities are use wheelchairs or walk with aids. The relationship between
      using walking aids and falling is somewhat inconsistent and poorly understood.
      PURPOSE: To investigate the use of walking aids as a risk factor for future falls
      among older adults living in residential aged care facilities and to identify
      spatiotemporal gait parameters that mediate the potential relationship between
      walking aids and falling. METHODS: Forty-three older adults (22 using walking
      aids and 21 not using walking aids) living in residential aged care facilities
      were enrolled in this study. Fall history, fear of falling, and the use of
      psychotropic agents were registered. Spatiotemporal gait (GAITRite(r)), grip
      strength (Jamar(r)), and cognitive status (Mini-Mental State Examination and
      Clock Drawing Test) were assessed. Falls were prospectively recorded during a 12
      month follow-up period using monthly calendars. RESULTS: Individuals using
      walking aids were older (P = .012), had a greater fear of falling (P = .017), and
      demonstrated a more conservative gait pattern compared with those not using
      walking aids. They walked slower (P < .001) and had a lower cadence (P < .001)
      and shorter step length (P = .018) and step time (P = .003). Twenty-two
      participants (15 using walking aids vs 7 not using walking aids) reported at
      least one fall ("fallers"). Univariate logistic regression identified using
      walking aids as a risk factor for future falls (odds ratio, 3.98; 95% confidence
      interval, 1.10-14.37; P = .035). A lower cadence, increased stance percentage,
      decreased swing percentage, increased age, and greater psychotropic drug intake
      were mediators that reduced the odds ratio of the relationship between using
      walking aids and faller status the most. CONCLUSIONS: Using walking aids is a
      risk factor for future falls among the older population living in residential
      settings. A substantial proportion of the relationship between walking aids and
      future falls could be explained by an altered spatiotemporal gait pattern,
      increased age, and psychotropic drug intake. This finding supports the aim of
      extensive training periods and appropriate instructions on the proper use of
      walking aids in terms of adequate and safe gait patterns.

PMID- 25594521
TI  - Measuring grip strength in older adults: comparing the grip-ball with the Jamar
      dynamometer.
AB  - BACKGROUND AND PURPOSE: Decreased grip strength is a predictor of adverse
      outcomes in older adults. A Grip-ball was developed that can be used for home
      based self-monitoring of grip strength to detect decline at an early stage. The
      purpose of this study was to evaluate the reliability and validity of
      measurements obtained with the Grip-ball in older adults. METHODS: Forty nursing
      home patients and 59 community-dwelling older adults 60 years or older were
      invited to participate in this study. Grip strength in both hands was measured 3
      consecutive times during a single visit using the Grip-ball and the Jamar
      dynamometer. Test-retest reliability was described using intraclass correlation
      coefficients. Concurrent validity was evaluated by calculating Pearson
      correlations between the mean Grip-ball and Jamar dynamometer measurements and
      between the highest measurements out of 3 trials. Known-groups validity was
      studied using t tests. RESULTS: Eighty eight participants (33 men) with a mean
      age of 75 (SD = 6.8) years were included. Intraclass correlation coefficients for
      the Grip-ball were 0.97 and 0.96 for the left and right hands, respectively (P <
      .001), and those for the Jamar dynamometer were 0.97 and 0.98 for the left and
      right hands, respectively (P < .001). Pearson correlations between the mean
      scores of the Grip-ball and the Jamar dynamometer were 0.71 (P < .001) and 0.76
      (P < .001) for the left and right hands, respectively. Pearson correlations
      between the highest scores out of 3 trials were 0.69 (P < .001) and 0.78 (P <
      .001) for the left and right hands, respectively. The t tests revealed that both
      the Grip-ball and the Jamar dynamometer detected grip strength differences
      between men and women but not between nursing home patients and community
      dwelling older adults. Grip-ball measurements did not confirm higher grip
      strength of the dominant hand whereas the Jamar dynamometer did. CONCLUSIONS: The
      Grip-ball provides reliable grip strength estimates in older adults. Correlations
      found between the Grip-ball and Jamar dynamometer measurements suggest acceptable
      concurrent validity. The Grip-ball seems capable of detecting "larger" grip
      strength differences but might have difficulty detecting "smaller" differences
      that were detected by the Jamar dynamometer. The Grip-ball could be used in
      practice to enable home-based self-monitoring of grip strength in older adults.
      However, for implementation of the Grip-ball as a screening and monitoring device
      in practice, it is important to gain insight into intersession reliability during
      home-based use of the Grip-ball and clinical relevance of changes in grip
      strength.

PMID- 25594522
TI  - Threshold of chair stand power necessary to perform activities of daily living
      independently in community-dwelling older women.
AB  - PURPOSE: To determine (1) the reproducibility of measurements of chair stand mean
      power (CSMP), (2) the relationships of CSMP with age, height, body mass, and body
      mass index, and (3) to identify the threshold of CSMP below which performing
      activities of daily living (ADL) is limited in older women. METHODS: Eighty-seven
      older women (70-88 years) were divided into an independent group (n = 48) who
      needed no assistance and a dependent group (n = 39) who needed assistance to
      perform ADL. The CSMP expressed in watts (velocity * load) for each repetition
      was assessed by a device that measures mean velocity. RESULTS: The intraclass
      correlation coefficient for CSMP suggested a high level of reproducibility (intra
      class correlation coefficient = 0.88-0.92, P < .05). Relationships existed
      between CSMP and age (r = -0.37; P < .001), CSMP and height (r = 0.31; P < .001),
      CSMP and body mass (r = 0.43; P < .001), and CSMP and body mass index (r = 0.30;
      P < .001). A receiver operator characteristic curve analysis revealed the optimal
      threshold criteria; a CSMP of 214 watts resulted in the highest combination of
      sensitivity (82.1%) and specificity (81.2%). CONCLUSION: The threshold of CSMP
      below which assistance is required to perform ADL in community-dwelling older
      women was identified.

PMID- 25594523
TI  - Grip strength values stratified by age, gender, and chronic disease status in
      adults aged 50 years and older.
AB  - BACKGROUND AND PURPOSE: Grip strength is a measure of overall muscle strength and
      has been found to be a predictor of disability and mortality. Almost 3 in 4
      adults aged 65 years and older have multiple chronic conditions, known as
      multimorbidity. Normative data for grip strength have commonly been reported on
      healthy convenience samples that may not accurately represent the population of
      interest. Grip strength values of US adults, utilizing a nationally
      representative data set based on the number of chronic diseases, would be
      beneficial to health care providers who serve adults with multimorbidity. The
      purpose of this study was to describe grip strength values of adults in the
      United States, based on gender, age, and the number of chronic diseases. METHODS:
      A cross-sectional analysis was conducted using data collected from adults aged 50
      years or older (n = 5877) from the Health and Retirement Study survey
      administered in 2008. Grip strength values (in kilograms) were determined and
      stratified on the basis of the number of self-reported chronic diseases (0, 1, 2,
      >=3) and stratified by age (decades) and gender. RESULTS: Consistent with
      previously published values, males demonstrated higher mean hand grip strength
      than females and grip strength values decreased with age. Adults with
      multimorbidity demonstrated decreased grip strength as compared with those
      without chronic conditions (males/females with 0 chronic diseases right grip
      strength (Equation is included in full-text article.)= 44.2/26.8 kg as compared
      with males/females with 3 or more chronic disease right grip strength (Equation
      is included in full-text article.)= 36.1/21.7 kg). CONCLUSIONS: The grip strength
      values presented can serve as a standard of comparison for the large proportion
      of adults who have multimorbidity. Clinicians should consider grip strength as a
      component of a comprehensive physical assessment to identify decreased grip
      strength and recommend increased physical activity as an appropriate
      intervention.

PMID- 25594524
TI  - Motivators and barriers for physical activity in older adults with osteoporosis.
AB  - BACKGROUND AND PURPOSE: Although physical activity (PA) is an important tool to
      counter osteoporosis, too few older patients with osteoporosis (OPWO) engage in
      PA. Little is known about specific motivators for and barriers to PA in OPWO,
      hindering the development of targeted PA promotion campaigns for these persons.
      Therefore, the main objective of this study was to identify motivators for and
      barriers to PA specifically in OPWO. METHODS: This qualitative study identified
      specific motivators for and barriers to PA in OPWO through 2 different methods:
      focus groups with professionals and in-depth interviews with OPWO. RESULTS: The
      OPWO tended to give a broad interpretation of what they considered as PA
      (practicing sports, physical work, and performing household activities), whereas
      the professionals seemed to mainly focus on (therapeutic) exercise as PA. Fifteen
      different motivators and 18 barriers have been identified. Among others, health
      improvement, social contact, habit, feeling good, and receiving medical advice
      from a medical doctor were motivators. Pain, fear of falling, bad weather, lack
      of interest, and caring for an ill partner were barriers to PA. For some older
      respondents, osteoporosis acted as a trigger for PA, and for others it was a
      barrier. CONCLUSIONS: This study emphasizes the importance for health care
      professionals to give personalized PA advice regarding the nature and frequency
      of PA that is safe and beneficial for osteoporosis. It stands to reason that the
      information about PA needs to be clear and consistent. Furthermore, it is
      quintessential to mention that it can take some time to adapt to physical
      exercise and to experience the beneficial effects, because pain sensations during
      the first PA sessions can be perceived as barriers to OPWO. Misconceptions or
      barriers to PA should be countered by assessing motivators for and barriers to PA
      by the health care professional together with the older client so that barriers
      can be eliminated and motivators can be strengthened. Physical activity education
      should involve not only the OPWO but also their relatives, friends, and important
      peers. Different social aspects of PA and the encouragements from peers are
      stimulating for older adults to initiate and to continue PA. The results of our
      study can constitute a starting point for further research to identify the
      motivators for and barriers to PA with the highest impact on PA behavior in OPWO,
      thus enabling evidence-based PA promotion campaigns for this patient group.

PMID- 25594525
TI  - Role of muscle stem cells during skeletal regeneration.
AB  - Although the importance of muscle in skeletal regeneration is well recognized
      clinically, the mechanisms by which muscle supports bone repair have remained
      elusive. Muscle flaps are often used to cover the damaged bone after traumatic
      injury yet their contribution to bone healing is not known. Here, we show that
      direct bone-muscle interactions are required for periosteum activation and callus
      formation, and that muscle grafts provide a source of stem cells for skeletal
      regeneration. We investigated the role of satellite cells, the muscle stem cells.
      Satellite cells loss in Pax7(-/-) mice and satellite cell ablation in Pax7(Cre)
      (ERT) (2/) (+) ;DTA(f/f) mice impaired bone regeneration. Although satellite
      cells did not contribute as a large source of cells endogenously, they exhibited
      a potential to contribute to bone repair after transplantation. The fracture
      healing phenotype in Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice was associated with
      decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and
      fibroblast growth factor 2 expression that are normally upregulated in response
      to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in
      Pax7(Cre) (ERT) (2/) (+) ;DTA(f/f) mice further supporting the role of satellite
      cells as a source of growth factors. These results provide the first functional
      evidence for a direct contribution of muscle to bone regeneration with important
      clinical implications as it may impact the use of muscle flaps, muscle stem
      cells, and growth factors in orthopedic applications.

PMID- 25594526
TI  - GnRH-antagonist programming versus GnRH agonist protocol: a randomized trial.
AB  - OBJECTIVE: Testing the ability to program IVF GnRH-antagonist cycles to avoid
      weekend oocyte retrieval. STUDY DESIGN: Preliminary randomized clinical trial.
      Patients presenting an indication for IVF or IVF-ICSI were assigned into either
      the Treatment Group - GnRH antagonist protocol, programmed to start stimulatory
      agents on a Friday, with oral 2mg estradiol valerate twice a day from the 2nd day
      of cycle until the first Friday to follow, or to the Control Group - long luteal
      GnRH agonist protocol. RESULTS: The performance of 27 Treatment Group patients
      and 24 Control Group patients was analyzed. Cycle dynamics were not clinically or
      statistically different except for a significant difference in the number of
      follicles measuring >=18 mm on hCG administration day. There were no differences
      in the number of aspirated ova, fertilization rates, embryo quality or number of
      embryos to be transferred. Pregnancy rate was 41.7% in the Treatment Group and
      50% in the Control Group (P>0.5). Only one patient assigned to the Treatment
      Group had a weekend retrieval. CONCLUSIONS: Preliminary results demonstrate no
      compromise related to follicular estrogen programming in a GnRH antagonist
      protocol and provide reassurance regarding the ability to achieve programming
      goals.

PMID- 25594527
TI  - Clinical pharmacology of theophylline in preterm infants: effects, metabolism and
      pharmacokinetics.
AB  - Recurrent apnea is common in preterm infants with consequent episodes of loss of
      effective breathing and the bronchodilator theophylline prevents apnea and
      reduces the number of apneic attacks. This drug also reduces hypoxaemic episodes.
      Theophylline acts on the lungs, kidneys and brain. Theophylline inhibits solute
      reabsorption in various segments of the nephron and a marked diuresis which
      occurs immediately after the administration of theophylline. This drug
      ameliorates kidney dysfunction and prophylaxis given early after birth,
      preventing vasomotor nephropathy. Theophylline reduces brain activity and reduces
      the spontaneous activity transients and alters the sleep-wake state in pre-term
      infants. Theophylline is extensively metabolized in premature infants and its
      major metabolic product is caffeine. The demethylation pathway occurring
      predominantly in adults is substituted by N-methylation to caffeine in premature
      infants. The halflife of theophylline is 5-fold longer in neonates than in adults
      and reaches the adult value at the age of 55 weeks. Theophylline may be
      administered trans-cutaneously by applying this drug to the back or abdomen of
      the infants and the mean fractional absorbance at 30 hours is 0.25. Theophylline
      is present in saliva and the concentration of this drug in saliva is similar to
      that in plasma, saliva may be used to monitor theophylline concentration. In
      conclusion, theophylline is a useful drug to treat apnea and ameliorate kidney
      dysfunction. 

PMID- 25594528
TI  - Laryngeal inflammation in the sudden infant death syndrome.
AB  - OBJECTIVE: Sudden infant death syndrome (SIDS) is marked by 'the sudden death of
      an infant that is unexpected by history and remains unexplained after a thorough
      forensic autopsy and a detailed death scene investigation'. The cause is unknown.
      Excessive subglottic submucosal glandular tissue and excessive sulphated mucus
      glycoprotein in the larynges of SIDS babies have been previously reported from
      our institution. We now report on laryngeal immunohistology. METHODS: Larynges
      from 7 children who died from Sudden Infant Death Syndrome (SIDS) at under 16
      weeks of age were examined immunohistologically and compared to those from 8 age-
      matched control infants who died from other causes. RESULTS: The SIDS babies had
      increased inflammatory changes in the laryngeal epithelium and sub- epithelium
      with raised numbers of cells staining for elastase (p<0.01), EG2(a marker for
      activated eosinophils) (p<0.01) and CD4(p<0.05) suggesting that some SIDS deaths
      involve preceding inflammation. CONCLUSIONS: Although death may be sudden and
      unexpected it appears that, at least in some SIDS victims, there is a preceding
      inflammatory process in the larynx which may allow hyper-reactivity of laryngeal
      reflexes and consequent apnoea. This observation concurs with others in the SIDS
      literature and offers a field for further research and possible prevention.

PMID- 25594529
TI  - Pediatric oral lichen planus: review and case report.
AB  - Oral Lichen Planus (OLP) is one of the most common dermatologic diseases
      occurring in the mouth with an overall prevalence of 0.5 - 2.2%. Childhood OLP is
      rare and follows an atypical course. OLP typically presents clinically as
      bilateral, symmetrical, flat- topped polygonal papules and plaques that may be
      symptomatic or asymptomatic. The aim of this article is to present a brief review
      of OLP with a case report of a 7 year old girl with OLP. 

PMID- 25594530
TI  - Surgical treatment of neonatal mastitis by periareolar drainage.
AB  - PURPOSE: Neonatal mastitis is a rare but challenging problem that commonly
      appears within the first 8 weeks after birth. Abscess formation in an infant's
      breast can lead to acute complications and longterm dysfunction. To our
      knowledge, no publication focuses on surgical techniques and postoperative care
      to avoid breast scarring in neonates. We herein present our surgical approach by
      periareolar drainage to avoid this long term complications. METHODS: After
      reviewing the medical database of our hospital from 2002 to 2012, 11 cases (6
      females and 5 males; 10 unilateral and 1 bilateral) of neonatal mastitis were
      found. Four cases required surgery, performed by periareolar drainage (n = 4,
      4:11). Our data were compared with data obtained from a literature review using
      Medline and Cochrane databases. RESULTS: In all our patients that underwent
      surgery, clinical symptoms were reduced directly after surgery. Our results were
      comparable with those reported in the literature, which included 163 patients
      (105 [64.42%] required surgery) from seven publications. Regarding our surgical
      technique, we have not observed any long-term complications during follow up
      examinations (range 12-116 months postoperative; mean, 77.36 months), which have
      been reported in the literature. CONCLUSIONS: Even if the acute infection can be
      cured by parenteral antibiotics and surgical incision if necessary, the longterm
      problems of scarring after mastitis, especially from surgical incisions at the
      site of maximum swelling, can lead to severe functional and aesthetic problems.
      To avoid such scarring, we herein present our surgical approach to mastitis by
      periareolar drainage.

PMID- 25594531
TI  - Patterning magnetic regions in hydrogenated graphene via e-beam irradiation.
AB  - Partially hydrogenated graphene is ferromagnetic and may be patterned by electron
      beam irradiation. Sequential patterning produces a patterned magnetic array.
      Removal of the hydrogen atoms also can convert electrically insulating fully
      hydrogenated graphene back into conductive graphene, enabling the writing of
      chemically isolated, dehydrogenated graphene nanoribbons as narrow as 100 nm. 

PMID- 25594532
TI  - Prenatal differentiation between truncus arteriosus (Types II and III) and
      pulmonary atresia with ventricular septal defect.
AB  - OBJECTIVE: To describe antenatal sonographic signs that help in the
      differentiation of truncus arteriosus Types II and III (TA-II/III) from pulmonary
      atresia with ventricular septal defect (PA-VSD). METHODS: From a database of
      fetal echocardiographic examinations, we identified fetuses with sonographic
      features of a single great artery with VSD and relatively normal four-chamber
      view. Records were reviewed, comparing fetuses with TA-II/III and those with PA
      VSD, with particular focus on: 1) characteristics of the overriding vessel, 2)
      appearance of the semilunar valves, 3) competence of the semilunar valves, 4)
      presence of major aortopulmonary collateral arteries (MAPCA), 5) main pulmonary
      artery being without antegrade flow, 6) site of arterial branching from the great
      artery and 7) other minor features, such as cardiac axis or associated anomalies.
      RESULTS: Seventeen fetuses were identified, eight with TA-II/III and nine with PA
      VSD. Among the eight fetuses with TA-II/III, seven had abnormal valves and six
      had valve regurgitation, compared with none of the nine PA-VSD fetuses. Five TA
      II/III fetuses had early branching to supply the lungs, whereas most fetuses with
      PA-VSD had more distal branching. Notably, in six of the TA-II/III fetuses, the
      root of the single great artery originated predominantly from the right
      ventricle, while all but one of the PA-VSD fetuses had typical equal overriding
      of the VSD. The main pulmonary artery was without antegrade flow in two cases
      with PA-VSD. Finally, four cases with PA-VSD had MAPCA, in two of which this was
      identified prenatally. CONCLUSION: Identification of abnormal arterial valves or
      valve regurgitation, site of origin of branching, presence of overriding of the
      great artery, a main pulmonary artery without antegrade flow and MAPCA are
      helpful in differentiating between TA-II/III and PA-VSD.

PMID- 25594534
TI  - The rapid and facile synthesis of oxyamine linkers for the preparation of
      hydrolytically stable glycoconjugates.
AB  - The synthesis of a number of N-glycosyl-N-alkyl-methoxyamine bifunctional linkers
      is described. The linkers contain an N-methoxyamine functional group for
      conjugation to carbohydrates and a terminal group, such as an amine, azide,
      thiol, or carboxylic acid, for conjugation to the probe of choice. The strategy
      for the linker synthesis is rapid (3-4 steps) and efficient (51-96% overall
      yield), and many of the linkers can be synthesized using a three-step one-pot
      strategy. Moreover, the linkers can be conjugated to glycans in excellent yield
      and they show excellent stability toward hydrolytic cleavage. 

PMID- 25594533
TI  - A "naked" Fe(III)-(O22-)-Cu(II) species allows for structural and spectroscopic
      tuning of low-spin heme-peroxo-Cu complexes.
AB  - Here we describe a new approach for the generation of heme-peroxo-Cu compounds,
      using a "naked" complex synthon, [(F8)Fe(III)-(O2(2-))-Cu(II)(MeTHF)3](+) (MeTHF
      = 2-methyltetrahydrofuran; F8 = tetrakis(2,6-difluorophenyl)porphyrinate).
      Addition of varying ligands (L) for Cu allows the generation and spectroscopic
      characterization of a family of high- and low-spin Fe(III)-(O2(2-))-Cu(II)(L)
      complexes. These possess markedly varying Cu(II) coordination geometries, leading
      to tunable Fe-O, O-O, and Cu-O bond strengths. DFT calculations accompanied by
      vibrational data correlations give detailed structural insights. 

PMID- 25594535
TI  - Agency, communion and entitlement.
AB  - In this study, the relationship between agency, communion, and the active,
      passive, and revenge forms of entitlement is examined. Results indicate that
      active entitlement was positively related to agency, negatively to communion
      (Study 1), and unrelated to unmitigated agency and communion (Study 2). Passive
      entitlement was positively related to communion (in regular and unmitigated
      forms) and negatively related to agency (in both forms). Revenge entitlement was
      positively related to agency (unmitigated and regular), and negatively related to
      both regular and unmitigated communal orientations. Detected relationships were
      independent from self-esteem (Study 1). The findings are discussed in relation to
      distinctions between narcissistic and healthy entitlement, and within the context
      of the three-dimensional model of entitlement. 

PMID- 25594539
TI  - Better check late than never: The chromosome segregation checkpoint (comment on
      DOI 10.1002/bies.201400140).

PMID- 25594536
TI  - Comparison of the capacity of enamel matrix derivative gel and enamel matrix
      derivative in liquid formulation to adsorb to bone grafting materials.
AB  - BACKGROUND: The use of an enamel matrix derivative (EMD) has been shown to
      enhance periodontal regeneration (e.g., formation of root cementum, periodontal
      ligament, and alveolar bone). However, in certain clinical situations, the use of
      EMD alone may not be sufficient to prevent flap collapse or provide sufficient
      stability of the blood clot. Data from clinical and preclinical studies have
      demonstrated controversial results after application of EMD combined with
      different types of bone grafting materials in periodontal regenerative
      procedures. The aim of the present study is to investigate the adsorption
      properties of enamel matrix proteins to bone grafts after surface coating with
      either EMD (as a liquid formulation) or EMD (as a gel formulation). METHODS:
      Three different types of grafting materials, including a natural bone mineral
      (NBM), demineralized freeze-dried bone allograft (DFDBA), or a calcium phosphate
      (CaP), were coated with either EMD liquid or EMD gel. Samples were analyzed by
      scanning electron microscopy or transmission electron microscopy (TEM) using an
      immunostaining assay with gold-conjugated anti-EMD antibody. Total protein
      adsorption to bone grafting material was quantified using an enzyme-linked
      immunosorbent assay (ELISA) kit for amelogenin. RESULTS: The adsorption of
      amelogenin to the surface of grafting material varied substantially based on the
      carrier system used. EMD gel adsorbed less protein to the surface of grafting
      particles, which easily dissociated from the graft surface after phosphate
      buffered saline rinsing. Analyses by TEM revealed that adsorption of amelogenin
      proteins were significantly farther from the grafting material surface, likely a
      result of the thick polyglycolic acid gel carrier. ELISA protein quantification
      assay demonstrated that the combination of EMD liquid + NBM and EMD liquid +
      DFDBA adsorbed higher amounts of amelogenin than all other treatment modalities.
      Furthermore, amelogenin proteins delivered by EMD liquid were able to penetrate
      the porous surface structure of NBM and DFDBA and adsorb to the interior of bone
      grafting particles. Grafting materials coated with EMD gel adsorbed more
      frequently to the exterior of grafting particles with little interior
      penetration. CONCLUSIONS: The present study demonstrates a large variability of
      adsorbed amelogenin to the surface of bone grafting materials when enamel matrix
      proteins were delivered in either a liquid formulation or gel carrier.
      Furthermore, differences in amelogenin adsorption were observed among NBM, DFDBA,
      and biphasic CaP particles. Thus, the potential for a liquid carrier system for
      EMD, used to coat EMD, may be advantageous for better surface coating.

PMID- 25594540
TI  - Development-dependent expression of DNA repair genes and epigenetic regulators in
      Arabidopsis plants exposed to ionizing radiation.
AB  - Both plant senescence and plant response to ionizing radiation involve changes in
      gene expression and epigenetic profiles, that rely on the formation of reactive
      oxygen species. However, how the developmental stage of a plant affects its
      response to ionizing radiation has not been extensively studied. In this study,
      our experiments showed that exposure to low (10 Gy) and high (100 Gy) doses of
      ionizing radiation causes developmental delays in plants that may result in
      reduced biomass or even death of the organism. In particular, 20-day-old plants,
      which are in the process of transitioning to reproductive growth, showed a
      distinct response to irradiation compared to 10- or 30-day-old irradiated plants
      that affects the expression of DNA repair genes. Specifically, we found that the
      expression of mismatch repair genes was increased in 20-day-old plants, while
      RAD51 was increased in 10- and 30-day-old plants. Furthermore, we found increased
      expression of MET1, CMT3 and SUVH5 epigenetic regulators that paralleled
      decreased ONSEN transcript levels in 20-day-old irradiated plants. These findings
      suggest that plants exposed during early reproductive growth exhibit a tighter
      control over genome stability in response to ionizing irradiation compared to
      plants irradiated at other developmental stages. 

PMID- 25594541
TI  - The miR-15 family enhances the radiosensitivity of breast cancer cells by
      targeting G2 checkpoints.
AB  - Enhancing radiosensitivity is an important area of investigation for improving
      breast cancer therapy outcomes. The aim of this study was to assess the role of
      the miR-15 family in the radiosensitivity of breast cancer cells. MicroRNAs
      (miRNAs) encoded by the miR-15 cluster are known to induce G1 arrest and
      apoptosis by targeting G1 checkpoints and the anti-apoptotic B cell lymphoma 2
      (BCL-2) gene. However, the effect of the miR-15 family on G2/M arrest and
      radiosensitivity remains poorly understood. In the current study, cells
      transfected with miR-15a/15b/16 mimic or inhibitor were irradiated and examined
      by: clonogenic assays, phosphorylated H2AX assay, flow cytometry, 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), real-time PCR and
      Western blot. Real-time PCR was also used to monitor time-dependent changes of
      miR-15a/15b/16 expression after irradiation. A putative target site for miR
      15a/15b/16 within the Chk1 and Wee1 3' UTRs was confirmed using luciferase
      reporter assays. Additionally, siRNA was used to validate the effect of Chk1 and
      Wee1 on radiosensitivity in breast cancer cells. In our study, we investigated
      the effects of radiation on the miR-15 family and found a time-dependent change
      in the expression of miR-15a/15b/16 in breast cancer cells postirradiation, as
      well as an increase in miR-15 family-mediated sensitization of breast cancer
      cells to radiation. The increase in radiosensitivity induced by the miR-15 family
      was associated with persistent unrepaired DNA damage, abrogation of radiation
      induced G2 arrest and suppressed cell proliferation, and appear to involve both
      the checkpoint kinase 1 (Chk1) and Wee1. In addition, we found that inhibition of
      the miR-15 family could not induce cell resistance to radiation. These findings
      suggest that the expression of the miR-15 family contributes to increased
      radiosensitivity of breast cancer cells by influencing G2/M checkpoint proteins. 

PMID- 25594542
TI  - Lysosomal-associated membrane protein 2 isoforms are differentially affected in
      early Parkinson's disease.
AB  - Lysosomes are the primary catabolic compartment for the degradation of
      intracellular proteins through autophagy. The presence of abnormal intracellular
      alpha-synuclein-positive aggregates in Parkinson's disease (PD) indicates that
      the degradative capacity of lysosomes is impaired in PD. Specific dysfunction of
      chaperone-mediated autophagy (CMA) in PD is suggested by reductions in the CMA
      membrane receptor, lysosomal-associated membrane protein (LAMP) 2A, although
      whether LAMP2A is the only LAMP2 isoform affected by PD is unknown. Messenger RNA
      (mRNA) and protein expression of all three LAMP2 isoforms was assessed in brain
      extracts from regions with and without PD-related increases in alpha-synuclein in
      autopsy samples from subjects in the early pathological stage of PD (n = 9),
      compared to age- and postmortem delay-matched controls (n = 10). In the early
      stages of PD, mRNA expression of all LAMP2 isoforms was not different from
      controls, with LAMP2B and LAMP2C protein levels also unchanged in PD. The
      selective loss of LAMP2A protein directly correlated with the increased levels of
      alpha-synuclein and decreased levels of the CMA chaperone heat shock cognate
      protein 70 in the same PD samples, as well as with the accumulation of cytosolic
      CMA substrate proteins. Our data show that LAMP2 protein isoforms are
      differentially affected in the early stages of PD, with LAMP2A selectively
      reduced in association with increased alpha-synuclein, and suggests that
      dysregulation of CMA-mediated protein degradation occurs before substantial alpha
      synuclein aggregation in PD.

PMID- 25594543
TI  - IgG4-related kidney disease--an update.
AB  - PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is a recently recognized
      systemic inflammatory disorder that can affect most organs/tissues such as
      sarcoidosis. The kidney is a frequently affected organ with tubulointerstitial
      nephritis (TIN), the representative lesion of IgG4-RD. This review focuses on the
      latest knowledge of IgG4-related kidney disease (IgG4-RKD). RECENT FINDINGS: A
      wide range of renal manifestations of IgG4-RD, that is TIN, membranous
      glomerulonephritis (MGN) and other glomerular lesions, and pyelitis, are
      collectively referred to as IgG4-RKD. Clinically, decreased renal function, or
      characteristic imaging findings such as multiple low-density lesions on contrast
      enhanced computed tomography or diffuse thickening of the renal pelvic wall, are
      typical presenting features. Although a rapid response to corticosteroid therapy
      is a very important feature of IgG4-TIN, in cases in which renal function is
      moderately to severely decreased before therapy, only partial recovery of renal
      function is obtained. SUMMARY: TIN with characteristic imaging findings is a
      typical manifestation of IgG4-RKD in the interstitium, while MGN is a
      representative manifestation of the glomerular lesions. Although IgG4 is a
      central feature of IgG4-RD, the recent discovery of IgG4-negative IgG4-RD raises
      questions about the causative role of the IgG4 molecule in this context.

PMID- 25594544
TI  - Antihypertensive mechanisms of intra-renal dopamine.
AB  - PURPOSE OF REVIEW: This review will highlight recent findings concerning the
      regulation and signalling of the intrarenal dopaminergic system and the emerging
      evidence for its importance in blood pressure regulation. RECENT FINDINGS: There
      is an increasing evidence that the intrarenal dopaminergic system plays an
      important role in the regulation of blood pressure, and defects in dopamine
      signalling appear to be involved in the development of hypertension. Recent
      experimental models have definitively demonstrated that abnormalities in
      intrarenal dopamine production or receptor signalling can predispose to salt
      sensitive hypertension and a dysregulated renin-angiotensin system. There are
      also new results indicating the importance of dopamine receptor mediated
      regulation of salt and water homeostasis along the nephron, and new studies
      indicating the role that the intrarenal dopaminergic system plays to mitigate the
      production of reactive oxygen species and progression of chronic renal disease.
      SUMMARY: New studies underscore the importance of the intrarenal dopaminergic
      system in the regulation of renal function and indicate how alterations in
      dopamine production or signalling may underlie the development of hypertension
      and kidney injury.

PMID- 25594547
TI  - Transition-metal-free access to primary anilines from boronic acids and a common
      (+)NH2 equivalent.
AB  - Diversely substituted anilines are prepared by treatment of functionalized
      arylboronic acids with a common, inexpensive source of electrophilic nitrogen
      (H2N-OSO3H, HSA) under basic aqueous conditions. Electron-rich substrates are
      found to be the most reactive by this method. However, even moderately electron
      poor substrates are well tolerated under the room temperature conditions.
      Sterically hindered substrates appear to be equally effective compared to
      unhindered ones. Highly electron-deficient substrates afford product in very low
      yields at room temperature, but moderate to good yields are obtained at refluxing
      temperatures. Our method is also amenable to electrophilic amination of several
      common boronic acid derivatives (e.g., pinacol esters). We demonstrate that it
      can be combined with metal-halogen exchange reactions or a variety of directed
      ortho metalation protocols in a "one-pot" sequence for the synthesis of aromatic
      amines with unique substitution patterns. DFT studies, in combination with
      experimental results, suggest that the reaction occurs via base-mediated
      activation of HSA, followed by 1,2 aryl B-N migration. This mode of activation
      appears to be critical for the success of the reaction and allows, for the first
      time, a general, electrophilic amination of boronic acids at ambient temperature.

PMID- 25594545
TI  - Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury.
AB  - Long-term molecular changes in the brain resulting from blast exposure may be
      mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation,
      that regulate gene expression. Aberrant regulation of gene expression is
      associated with behavioral abnormalities, where DNA methylation bridges
      environmental signals to sustained changes in gene expression. We assessed DNA
      methylation changes in the brains of rats exposed to three 74.5 kPa blast
      overpressure events, conditions that have been associated with long-term
      anxiogenic manifestations weeks or months following the initial exposures. Rat
      frontal cortex eight months post-exposure was used for cell sorting of whole
      brain tissue into neurons and glia. We interrogated DNA methylation profiles in
      these cells using Expanded Reduced Representation Bisulfite Sequencing. We
      obtained data for millions of cytosines, showing distinct methylation profiles
      for neurons and glia and an increase in global methylation in neuronal versus
      glial cells (p<10(-7)). We detected DNA methylation perturbations in blast
      overpressure-exposed animals, compared with sham blast controls, within 458 and
      379 genes in neurons and glia, respectively. Differentially methylated neuronal
      genes showed enrichment in cell death and survival and nervous system development
      and function, including genes involved in transforming growth factor beta and
      nitric oxide signaling. Functional validation via gene expression analysis of 30
      differentially methylated neuronal and glial genes showed a 1.2 fold change in
      gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast
      animals (p<0.05). These data provide the first genome-based evidence for changes
      in DNA methylation induced in response to multiple blast overpressure exposures.
      In particular, increased methylation and decreased gene expression were observed
      in the Aanat gene, which is involved in converting serotonin to the circadian
      hormone melatonin and is implicated in sleep disturbance and depression
      associated with traumatic brain injury. 

PMID- 25594548
TI  - Hierarchical micron-sized mesoporous/macroporous graphene with well-tuned surface
      oxygen chemistry for high capacity and cycling stability Li-O2 battery.
AB  - Nonaqueous Li-O2 battery is recognized as one of the most promising energy
      storage devices for electric vehicles due to its super-high energy density. At
      present, carbon or catalyst-supporting carbon materials are widely used for
      cathode materials of Li-O2 battery. However, the unique electrode reaction and
      complex side reactions lead to numerous hurdles that have to be overcome. The
      pore blocking caused by the solid products and the byproducts generated from the
      side reactions severely limit the capacity performance and cycling stability.
      Thus, there is a great need to develop carbon materials with optimized pore
      structure and tunable surface chemistry to meet the special requirement of Li-O2
      battery. Here, we propose a strategy of vacuum-promoted thermal expansion to
      fabricate one micron-sized graphene matrix with a hierarchical meso-/macroporous
      structure, combining with a following deoxygenation treatment to adjust the
      surface chemistry by reducing the amount of oxygen and selectively removing
      partial unstable groups. The as-made graphene demonstrates dramatically tailored
      pore characteristics and a well-tuned surface chemical environment. When applied
      in Li-O2 battery as cathode, it exhibits an outstanding capacity up to 19 800 mA
      h g(-1) and is capable of enduring over 50 cycles with a curtaining capacity of
      1000 mA h g(-1) at a current density of 1000 mA g(-1). This will provide a novel
      pathway for the design of cathodes for Li-O2 battery. 

PMID- 25594546
TI  - Measurement of technetium-99m sestamibi signals in rats administered a
      mitochondrial uncoupler and in a rat model of heart failure.
AB  - BACKGROUND: Many methods have been used to assess mitochondrial function.
      Technetium-99m sestamibi ((99m)Tc-MIBI), a lipophilic cation, is rapidly
      incorporated into myocardial cells by diffusion and mainly localizes to the
      mitochondria. The purpose of this study was to investigate whether measurement of
      (99m)Tc-MIBI signals in animal models could be used as a tool to quantify
      mitochondrial membrane potential at the organ level. METHODS AND RESULTS: We
      analyzed (99m)Tc-MIBI signals in Sprague-Dawley (SD) rat hearts perfused with
      carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known
      to reduce the mitochondrial membrane potential. (99m)Tc-MIBI signals could be
      used to detect changes in the mitochondrial membrane potential with sensitivity
      comparable to that obtained by two-photon laser microscopy with the cationic
      probe tetramethylrhodamine ethyl ester (TMRE). We also measured (99m)Tc-MIBI
      signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or
      vehicle. (99m)Tc-MIBI signals decreased in rat hearts administered CCCP, and the
      ATP content, as measured by (31)P magnetic resonance spectroscopy, decreased
      simultaneously. Next, we administered (99m)Tc-MIBI to Dahl salt-sensitive rats
      fed a high-salt diet, which leads to hypertension and heart failure. The (99m)Tc
      MIBI signal per heart tissue weight was inversely correlated with heart weight,
      cardiac function, and the expression of atrial natriuretic factor, a marker of
      heart failure, and positively correlated with the accumulation of labeled fatty
      acid analog. The (99m)Tc-MIBI signal per liver tissue weight was lower than that
      per heart tissue weight. CONCLUSION: Measurement of (99m)Tc-MIBI signals can be
      an effective tool for semiquantitative investigation of cardiac mitochondrial
      membrane potential in the SD rat model by using a chemical to decrease the
      mitochondrial membrane potential. The (99m)Tc-MIBI signal per heart tissue weight
      was inversely correlated with the severity of heart failure in the Dahl rat
      model.

PMID- 25594550
TI  - Increased risk of all-cause mortality and renal graft loss in stable renal
      transplant recipients with hyperparathyroidism.
AB  - BACKGROUND: Hyperparathyroidism is reported in 10% to 66% of renal transplant
      recipients (RTR). The influence of persisting hyperparathyroidism on long-term
      clinical outcomes in RTR has not been examined in a large prospective study.
      METHODS: We investigated the association between baseline parathyroid hormone
      (PTH) levels and major cardiovascular events, renal graft loss, and all-cause
      mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived
      from the Assessment of LEscol in Renal Transplantation trial. Patients were
      recruited in a mean of 5.1 years after transplantation, and follow-up time was 6
      to 7 years. RESULTS: Significant associations between PTH and all 3 outcomes were
      found in univariate analyses. When adjusting for a range of plausible
      confounders, including measures of renal function and serum mineral levels, PTH
      remained significantly associated with all-cause mortality (4% increased risk per
      10 units; P=0.004), and with graft loss (6% increased risk per 10 units;
      P<0.001), but not with major cardiovascular events. Parathyroid hormone above the
      upper limit of normal (65 pg/mL) indicated a 46% (P=0.006) higher risk of death
      and an 85% higher risk of graft loss (P<0.001) compared with low/normal values.
      CONCLUSIONS: Hyperparathyroidism is an independent, potentially remediable, risk
      factor for renal graft loss and all-cause mortality in RTR.

PMID- 25594549
TI  - Inclusion of dynamic clinical data improves the predictive performance of a 30
      day readmission risk model in kidney transplantation.
AB  - BACKGROUND: Thirty-day readmissions (30DRA) are a highly scrutinized measure of
      healthcare quality and relatively frequent among kidney transplants (KTX).
      Development of predictive risk models is critical to reducing 30DRA and improving
      outcomes. Current approaches rely on fixed variables derived from administrative
      data. These models may not capture clinical evolution that is critical to
      predicting outcomes. METHODS: We directed a retrospective analysis toward: (1)
      developing parsimonious risk models for 30DRA and (2) comparing efficiency of
      models based on the use of immutable versus dynamic data. Baseline and in
      hospital clinical and outcomes data were collected from adult KTX recipients
      between 2005 and 2012. Risk models were developed using backward logistic
      regression and compared for predictive efficacy using receiver operating
      characteristic curves. RESULTS: Of 1147 KTX patients, 123 had 30DRA. Risk factors
      for 30DRA included recipient comorbidities, transplant factors, and index
      hospitalization patient level clinical data. The initial fixed variable model
      included 9 risk factors and was modestly predictive (area under the curve, 0.64;
      95% confidence interval [95% CI], 0.58-0.69). The model was parsimoniously
      reduced to 6 risks, which remained modestly predictive (area under the curve,
      0.63; 95% CI, 0.58-0.69). The initial predictive model using 13 fixed and dynamic
      variables was significantly predictive (AUC, 0.73; 95% CI, 0.67-0.80), with
      parsimonious reduction to 9 variables maintaining predictive efficacy (AUC, 0.73;
      95% CI, 0.67-0.79). The final model using dynamically evolving clinical data
      outperformed the model using static variables (P=0.009). Internal validation
      demonstrated that the final model was stable with minimal bias. CONCLUSIONS: We
      demonstrate that modeling dynamic clinical data outperformed models using
      immutable data in predicting 30DRA.

PMID- 25594551
TI  - Long-term kidney allograft survival in patients with transplant glomerulitis.
AB  - BACKGROUND: Renal transplant glomerulitis (G) is associated with acute antibody
      mediated rejection (ABMR) in the presence of donor-specific antibodies. However,
      the long-term prognosis of isolated G (isG) in the absence of donor-specific
      antibodies or G in combination with T cell-mediated rejection (TCMR) remains
      unexplored. METHODS: Seventy recipients with G were included in this
      retrospective study and subdivided into 3 groups: isG, G with TCMR (G+TCMR), and
      G with acute ABMR. The control groups were: patients with TCMR Banff type I or II
      without G (TCMR) and patients without rejection (NR). Kaplan-Meier death-censored
      survival plots and Cox regression were used to analyze graft survival. The
      combined graft survival endpoint was defined as a return to dialysis or estimated
      glomerular filtration rate less than 15 mL/min/1.73 m. The median follow-up was
      37 (14; 77) months from biopsy. RESULTS: Graft survival was significantly lower
      in patients with G than in the NR and TCMR groups. No significant differences
      were observed among the isG, G+TCMR, and ABMR groups. Graft survival was lower in
      the G+TCMR group than in the TCMR group. Glomerulitis was independently
      associated with the risk of adverse graft outcome in a multivariate Cox
      regression model adjusted for other confounders (hazard ratio, 4.52 [95%
      confidence interval, 2.37-8.68] vs controls; P<0.001). CONCLUSIONS: Glomerulitis
      is strongly associated with increased risk of graft failure. Graft survival in
      patients with isG that do not meet the Banff criteria for acute/active ABMR and
      in patients with G accompanying TCMR is comparable to the ABMR group.

PMID- 25594552
TI  - Choosing the order of deceased donor and living donor kidney transplantation in
      pediatric recipients: a Markov decision process model.
AB  - BACKGROUND: Most pediatric kidney transplant recipients eventually require
      retransplantation, and the most advantageous timing strategy regarding deceased
      and living donor transplantation in candidates with only 1 living donor remains
      unclear. METHODS: A patient-oriented Markov decision process model was designed
      to compare, for a given patient with 1 living donor, living-donor-first followed
      if necessary by deceased donor retransplantation versus deceased-donor-first
      followed if necessary by living donor (if still able to donate) or deceased donor
      (if not) retransplantation. Based on Scientific Registry of Transplant Recipients
      data, the model was designed to account for waitlist, graft, and patient
      survival, sensitization, increased risk of graft failure seen during late
      adolescence, and differential deceased donor waiting times based on pediatric
      priority allocation policies. Based on national cohort data, the model was also
      designed to account for aging or disease development, leading to ineligibility of
      the living donor over time. RESULTS: Given a set of candidate and living donor
      characteristics, the Markov model provides the expected patient survival over a
      time horizon of 20 years. For the most highly sensitized patients (panel reactive
      antibody > 80%), a deceased-donor-first strategy was advantageous, but for all
      other patients (panel reactive antibody < 80%), a living-donor-first strategy was
      recommended. CONCLUSIONS: This Markov model illustrates how patients, families,
      and providers can be provided information and predictions regarding the most
      advantageous use of deceased donor versus living donor transplantation for
      pediatric recipients.

PMID- 25594553
TI  - Immune reconstitution/immunocompetence in recipients of kidney plus hematopoietic
      stem/facilitating cell transplants.
AB  - Nineteen subjects have more than 18 months' follow-up in a phase IIb tolerance
      protocol in HLA-mismatched recipients of living donor kidney plus facilitating
      cell enriched hematopoietic stem cell allografts (FCRx). Reduced intensity
      conditioning preceded a kidney allograft, followed the next day by FCRx. Twelve
      have achieved stable donor chimerism and have been successfully taken off
      immunosuppression (IS). We prospectively evaluated immune reconstitution and
      immunocompetence. Return of CD4 and CD8 T central and effector memory cell
      populations was rapid. T-cell receptor (TCR) Excision Circle analysis showed a
      significant proportion of chimeric cells produced were being produced de novo.
      The TCR repertoires posttransplant in chimeric subjects were nearly as diverse as
      pretransplant donors and recipients, and were comparable to subjects with
      transient chimerism who underwent autologous reconstitution. Subjects with
      persistent chimerism developed few serious infections when off IS. The majority
      of infectious complications occurred while subjects were still on conventional
      IS. BK viruria and viremia resolved after cessation of IS and no tissue-invasive
      cytomegalovirus infections occurred. Notably, although 2 of 4 transiently or
      nonchimeric subjects experienced recurrence of their underlying autoimmune
      disorders, none of the chimeric subjects have, suggesting that self-tolerance is
      induced in addition to tolerance to alloantigen. No persistently chimeric subject
      has developed donor-specific antibody, and renal function has remained within
      normal limits. Patients were successfully vaccinated per The American Society for
      Blood and Marrow Transplantation guidelines without loss of chimerism or
      rejection. Memory for hepatitis vaccination persisted after transplantation.
      Chimeric subjects generated immune responses to pneumococcal vaccine. These data
      suggest that immune reconstitution and immunocompetence are maintained in
      persistently chimeric subjects. 

PMID- 25594554
TI  - Outcomes in kidney transplant recipients from older living donors.
AB  - BACKGROUND: Previous studies demonstrate that graft survival from older living
      kidney donors (LD; age>60 years) is worse than younger LD but similar to deceased
      standard criteria donors (SCD). Limited sample size has precluded more detailed
      analyses of transplants from older LD. METHODS: Using the United Network for
      Organ Sharing database from 1994 to 2012, recipients were categorized by donor
      status: SCD, expanded criteria donor (ECD), or LD (by donor age: <60, 60-64, 65
      69, >=70 years). Adjusted models, controlling for donor and recipient risk
      factors, evaluated graft and recipient survivals. RESULTS: Of 250,827 kidney
      transplants during the study period, 92,646 were LD kidneys, with 4.5% of these
      recipients (n=4,186) transplanted with older LD kidneys. The use of LD donors 60
      years or older increased significantly from 3.6% in 1994 to 7.4% in 2011.
      Transplant recipients with older LD kidneys had significantly lower graft and
      overall survival compared to younger LD recipients. Compared to SCD recipients,
      graft survival was decreased in recipients with LD 70 years or older, but overall
      survival was similar. Older LD kidney recipients had better graft and overall
      survival than ECD recipients. CONCLUSIONS: As use of older kidney donors
      increases, overall survival among kidney transplant recipients from older living
      donors was similar to or better than SCD recipients, better than ECD recipients,
      but worse than younger LD recipients. With increasing kidney donation from older
      adults to alleviate profound organ shortages, the use of older kidney donors
      appears to be an equivalent or beneficial alternative to awaiting deceased donor
      kidneys.

PMID- 25594555
TI  - Outcomes of pancreas retransplantation.
AB  - BACKGROUND: Pancreas retransplantation is associated with increased rates of
      technical failure and rejection compared to other organ transplants. As such, it
      is not routinely done, and outcomes are mostly known through registry data. Here
      we analyze the outcomes of primary versus retransplant for all pancreas
      transplants done in our program over nearly 35 years. METHODS: Donor and
      recipient characteristics and outcomes data were prospectively gathered and
      recorded in our institutional database. Outcomes of primary and retransplants
      were reported overall, and then subgrouped by number (second, third, fourth). An
      in-depth analysis of transplants done after 2003 was included. Rates of technical
      failure, 1 year acute rejection, graft survival, and patient survival were
      compared. RESULTS: Two thousand one hundred forty-five pancreas transplants were
      performed at our institution between 1978 and 2012. Four hundred fifteen of these
      were retransplants. Improvements were seen in technical failure rates and graft
      survival for both primary and retransplants over time. There were no significant
      differences in technical failure or patient survival for primary versus
      retransplants overall, or by transplant number (second, third, fourth). Modern
      era retransplants had more acute rejection in the first year after
      transplantation. Retransplants (vs primary) had decreased mid-term death censored
      graft survival. Transplant type continues to be an important driver of outcome.
      CONCLUSIONS: Retransplant outcomes have improved over time, yet increased
      rejection and immunologic graft loss rates remain associated with pancreas
      retransplantation. In contrast, risk of technical failure and patient death for
      primary versus retransplants are similar. Therefore, pancreas retransplantation
      in highly selected candidates should be considered in experienced centers.

PMID- 25594556
TI  - Establishment of a global virtual laboratory for transplantation: a symposium
      report.
AB  - Advancing the field of transplantation by developing improved and novel treatment
      strategies will require a detailed understanding of changes and adaptations of
      alloimmunity, both over the short-term and long-term. Presently, we rely on
      traditional measures that may not optimally reflect benefits of new treatments.
      Thus, collecting reliable basic information about changes of the immune response
      along the entire posttransplantation course will improve our understanding of how
      immune mechanisms evolve and guide the introduction of novel clinical approaches.
      The gathering of good quality data from transplant recipients in various clinical
      trials will require immune monitoring that is reliable and comparable so that
      large sets of information from individual trials can be confidently analyzed to
      reach rigorous conclusions. A uniform standard of testing is thus a prerequisite
      toward this goal. Based on the assumption that the transplantation community will
      in general be supportive of this concept, this meeting proposed establishing a
      global virtual laboratory as a means of developing and disseminating detailed and
      rigorous protocols for the monitoring of alloimmune responses. 

PMID- 25594557
TI  - Donor-derived transmission events in 2013: a report of the Organ Procurement
      Transplant Network Ad Hoc Disease Transmission Advisory Committee.
AB  - BACKGROUND: The Organ Procurement Transplant Network Disease Transmission
      Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential
      donor-derived transmission events (PDDTE), including infections and malignancies,
      to assess for donor transmitted events. METHODS: Reports of unexpected PDDTE to
      Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A
      standardized algorithm was used to assess each PDDTE from a given donor and to
      classify each individual recipient from that donor. RESULTS: Of 443 total PDDTE
      submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully
      evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of
      infection, malignancy or other conditions to 42 recipients. Of 204 infection
      events, 24 were classified as P/P affecting 30 recipients, with four deaths.
      Bacteria were the most frequently reported type of infection, accounting for 99
      reports but only 12 recipients from 11 donors experienced P/P transmission. There
      were 65 donors reported with potential malignancy events and 5 were classified as
      P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there
      were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4
      recipients and 1 death. CONCLUSIONS: There was a 43% increase in the number of
      PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P
      transmission remains low, affecting recipients from 32 donors especially when
      compared with the more than 14,000 donors recovered annually in the United
      States. The continued use of the new standard algorithm and triaging process will
      enhance the reproducibility of DTAC assessments and allow more robust analysis of
      our aggregate DTAC experience.

PMID- 25594558
TI  - SRrp35 suppresses cell proliferation and malignancy in hepatocellular carcinoma.
AB  - AIM: Serine/arginine-rich (SR) proteins are known to be involved in alternative
      pre-mRNA splicing, RNA metabolism and cancer development. SRrp35 is a member of
      this family that antagonizes classical SR proteins in the regulation of splicing.
      However, the function of SRRP35 in cancer remains unclear to date. This study
      aims to investigate SRrp35 function in hepatocellular carcinoma (HCC). METHODS:
      SRrp35 expression was accessed by quantitative real-time polymerase chain
      reaction in 32 pairs of clinical HCC samples and 12 kinds of HCC cell lines. The
      biological roles of Srrp35 were analyzed using cell viability, colony formation
      and soft agar growth assays in vitro and tumorigenicity in nude mice model.
      RESULTS: SRrp35 was frequently downregulated in 62.5% (20/32) of HCC specimens
      and most of HCC cell lines. Enhanced expression of SRrp35 significantly
      suppressed cell proliferation and colony formation in an anchor-dependent and 
      independent manner, whereas knockdown of SRrp35 by RNA inference resulted in the
      opposite effects. In vivo, SRrp35 plays a suppressive role in developing tumor
      xenografts in line with the function in vitro. CONCLUSION: Our findings suggest
      that SRrp35 suppresses cell proliferation and malignancy in HCC and could be a
      potential therapeutic target for this disease.

PMID- 25594560
TI  - Editorial: Exotica fantasia extract.

PMID- 25594559
TI  - Complete perchlorate reduction using methane as the sole electron donor and
      carbon source.
AB  - Using a CH4-based membrane biofilm reactor (MBfR), we studied perchlorate (ClO4(
      )) reduction by a biofilm performing anaerobic methane oxidation coupled to
      denitrification (ANMO-D). We focused on the effects of nitrate (NO3(-)) and
      nitrite (NO2(-)) surface loadings on ClO4(-) reduction and on the biofilm
      community's mechanism for ClO4(-) reduction. The ANMO-D biofilm reduced up to 5
      mg/L of ClO4(-) to a nondetectable level using CH4 as the only electron donor and
      carbon source when CH4 delivery was not limiting; NO3(-) was completely reduced
      as well when its surface loading was <= 0.32 g N/m(2)-d. When CH4 delivery was
      limiting, NO3(-) inhibited ClO4(-) reduction by competing for the scarce electron
      donor. NO2(-) inhibited ClO4(-) reduction when its surface loading was >= 0.10 g
      N/m(2)-d, probably because of cellular toxicity. Although Archaea were present
      through all stages, Bacteria dominated the ClO4(-)-reducing ANMO-D biofilm, and
      gene copies of the particulate methane mono-oxygenase (pMMO) correlated to the
      increase of respiratory gene copies. These pieces of evidence support that ClO4(
      ) reduction by the MBfR biofilm involved chlorite (ClO2(-)) dismutation to
      generate the O2 needed as a cosubstrate for the mono-oxygenation of CH4.

PMID- 25594562
TI  - Morphological Identities of Two Different Marine Stramenopile Environmental
      Sequence Clades: Bicosoeca kenaiensis (Hilliard, 1971) and Cantina marsupialis
      (Larsen and Patterson, 1990) gen. nov., comb. nov.
AB  - Although environmental DNA surveys improve our understanding of biodiversity,
      interpretation of unidentified lineages is limited by the absence of associated
      morphological traits and living cultures. Unidentified lineages of marine
      stramenopiles are called "MAST clades". Twenty-five MAST clades have been
      recognized: MAST-1 through MAST-25; seven of these have been subsequently
      discarded because the sequences representing those clades were found to either
      (1) be chimeric or (2) affiliate within previously described taxonomic groups.
      Eighteen MAST clades remain without a cellular identity. Moreover, the discarded
      "MAST-13" has been used in different studies to refer to two different
      environmental sequence clades. After establishing four cultures representing two
      different species of heterotrophic stramenopiles and then characterizing their
      morphology and molecular phylogenetic positions, we determined that the two
      different species represented the two different MAST-13 clades: (1) a lorica
      bearing Bicosoeca kenaiensis and (2) a microaerophilic flagellate previously
      named "Cafeteria marsupialis". Both species were previously described with only
      light microscopy; no cultures, ultrastructural data or DNA sequences were
      available from these species prior to this study. The molecular phylogenetic
      position of three different "C. marsupialis" isolates was not closely related to
      the type species of Cafeteria; therefore, we established a new genus for these
      isolates, Cantina gen. nov.

PMID- 25594564
TI  - A spectroscopic study of the cis/trans-isomers of penta-2,4-dienoic acid attached
      to gold nanoclusters.
AB  - In this theoretical work, we present a spectroscopic analysis of the cis/trans
      isomers of a molecular switch, penta-2,4-dienoic acid, attached to gold clusters
      of different size (1, 2 and 20 gold atoms). We have simulated 4 different
      spectroscopic techniques: Infrared spectroscopy, normal Raman scattering,
      absorption spectra and resonance Raman scattering. We discuss how the position
      and the conformation of the molecule determine the electronic structure and
      hence, the spectra. The calculations have been performed using density functional
      theory for the properties of the ground state and time-dependent density
      functional theory for the excited-state properties. Special emphasis is put on
      the resonance Raman spectra for the study of the isomers. In the present case,
      resonance Raman scattering is best suited to discriminate between the isomers on
      the gold clusters. 

PMID- 25594565
TI  - Rural collaborative guideline implementation: Evaluation of a hub and spoke
      multidisciplinary team model of care for orthogeriatric inpatients - A before and
      after study of adherence to clinical practice guidelines.
AB  - OBJECTIVE: To evaluate whether adherence to orthogeriatric inpatient clinical
      practice guidelines increased after the implementation of an innovative hub and
      spoke multidisciplinary team, the Sub-Acute Care Team (SCT). DESIGN: This study
      used a before and after design and describes a medical record audit. SETTING:
      Rural inpatient facilities with 20-50 inpatient beds. PARTICIPANTS: Inpatients
      aged 65 years and older who sustained a lower limb fracture from a fall were
      admitted to a regional facility and subsequent rural facility. The audit included
      42 inpatients admitted before the SCT (April 2009-April 2010) and 35 inpatients
      admitted after the SCT (April 2011-April 2012). INTERVENTIONS: The SCT used
      interprofessional collaborative practice and orthogeriatric clinical practice
      guidelines to inform inpatient care. MAIN OUTCOME MEASURE(S): Adherence was
      measured by answering 10 questions representative of the guidelines. Chi-square
      or Fisher's exact tests were used for each question to identify if the proportion
      of inpatients receiving guideline-based care changed significantly after SCT
      implementation. RESULTS: After SCT implementation, an increase in the adherence
      to guidelines was statistically significant (P < 0.05) for handover, nutrition
      support, falls prevention, bladder management and more than five guideline-based
      care questions. CONCLUSIONS: Adherence to orthogeriatric inpatient clinical
      practice guidelines increased after the implementation of the SCT. The mechanisms
      likely to have contributed include the comprehensive multidisciplinary handover
      and the opportunity for rural inpatient clinical follow-up. This model is likely
      to be effective in improving care for other frail rural inpatient populations.

PMID- 25594566
TI  - A plasmid containing the human metallothionein II gene can function as an
      antibody-assisted electrophoretic biosensor for heavy metals.
AB  - Different forms of heavy metals affect biochemical systems in characteristic ways
      that cannot be detected with typical metal analysis methods like atomic
      absorption spectrometry. Further, using living systems to analyze interaction of
      heavy metals with biochemical systems can be laborious and unreliable. To
      generate a reliable easy-to-use biologically-based biosensor system, the entire
      human metallothionein-II (MT-II) gene was incorporated into a plasmid (pUC57-MT)
      easily replicated in Escherichia coli. In this system, a commercial polyclonal
      antibody raised against human metal-responsive transcription factor-1 protein
      (MTF-1 protein) could modify the electrophoretic migration patterns (i.e. cause
      specific decreases in agarose gel electrophoretic mobility) of the plasmid in the
      presence or absence of heavy metals other than zinc (Zn). In the study here,
      heavy metals, MTF-1 protein, and polyclonal anti-MTF-1 antibody were used to
      assess pUC57-MT plasmid antibody-assisted electrophoretic mobility. Anti-MTF-1
      antibody bound both MTF-1 protein and pUC57-MT plasmid in a non-competitive
      fashion such that it could be used to differentiate specific heavy metal binding.
      The results showed that antibody-inhibited plasmid migration was heavy metal
      level-dependent. Zinc caused a unique mobility shift pattern opposite to that of
      other metals tested, i.e. Zn blocked the antibody ability to inhibit plasmid
      migration, despite a greatly increased affinity for DNA by the antibody when Zn
      was present. The Zn effect was reversed/modified by adding MTF-1 protein.
      Additionally, antibody inhibition of plasmid mobility was resistant to heat pre
      treatment and trypsinization, indicating absence of residual DNA extraction
      resistant bacterial DNA binding proteins. DNA binding by anti-DNA antibodies may
      be commonly enhanced by xenobiotic heavy metals and elevated levels of Zn, thus
      making them potentially effective tools for assessment of heavy metal
      bioavailability in aqueous solutions and fluid obtained from metal implant sites.

PMID- 25594567
TI  - Suppression of antigen-specific antibody responses in mice exposed to
      perfluorooctanoic acid: Role of PPARalpha and T- and B-cell targeting.
AB  - T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice
      exposed to >=3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To
      determine if suppression of humoral immunity by PFOA is peroxisome proliferator
      activated receptor alpha (PPARalpha)-dependent and if suppression is associated
      with specific targeting of T- or B-cells, three separate experiments were
      conducted: (1) female PPARalpha constitutive knockout (PPARalpha KO; B6.129S4
      Ppar(tm1Gonz)N12) and wild-type controls (WT; C57BL/6-Tac) exposed to 0, 7.5, or
      30 mg PFOA/kg for 15 days were immunized on Day 11 with a T-cell-dependent
      antigen and sera then collected for measures of antigen-specific IgM titers
      (TDAR) 5 days later; (2) female C57BL/6N WT mice exposed to 0, 0.94, 1.88, 3.75,
      or 7.5 mg PFOA/kg for 15 days were immunized with a T-cell-independent antigen on
      Day 11 and sera were then collected for analyses of antigen-specific IgM titers
      (TIAR) 7 days later; and (3) splenic lymphocyte phenotypes were assessed in
      unimmunized female C57BL/6N WT mice exposed to 0, 3.75, or 7.5 mg PFOA/kg for 10
      days to investigate effects of PFOA in the absence of specific immunization.
      Separate groups of mice were immunized with a T-cell-dependent antigen after 11
      days of exposure and splenic lymphocyte sub-populations were assessed after 13 or
      15 days of exposure to assess numbers of stimulated cells. The results indicated
      that exposure to >=1.88 mg PFOA/kg suppressed the TIAR; exposure to 30 mg PFOA/kg
      suppressed the TDAR in both PPARalpha KO and WT mice. The percentage of splenic B
      cells was unchanged. Results obtained in the PPARalpha KO mice indicated that
      PPARalpha suppression of TDAR was independent of PPARalpha involvement.
      Suppression of the TIAR and the TDAR with minimal lymphocyte sub-population
      effects suggested that effects on humoral immunity are likely mediated by
      disruption of B-cell/plasma cell function. 

PMID- 25594568
TI  - Substrate Effects in the Supramolecular Assembly of 1,3,5-Benzene Tricarboxylic
      Acid on Graphite and Graphene.
AB  - The behavior of small molecules on a surface depends critically on both molecule
      substrate and intermolecular interactions. We present here a detailed comparative
      investigation of 1,3,5-benzene tricarboxylic acid (trimesic acid, TMA) on two
      different surfaces: highly oriented pyrolytic graphite (HOPG) and single-layer
      graphene (SLG) grown on a polycrystalline Cu foil. On the basis of high
      resolution scanning tunnelling microscopy (STM) images, we show that the epitaxy
      matrix for the hexagonal TMA chicken wire phase is identical on these two
      surfaces, and, using density functional theory (DFT) with a non-local van der
      Waals correlation contribution, we identify the most energetically favorable
      adsorption geometries. Simulated STM images based on these calculations suggest
      that the TMA lattice can stably adsorb on sites other than those identified to
      maximize binding interactions with the substrate. This is consistent with our net
      energy calculations that suggest that intermolecular interactions (TMA-TMA dimer
      bonding) are dominant over TMA-substrate interactions in stabilizing the system.
      STM images demonstrate the robustness of the TMA films on SLG, where the
      molecular network extends across the variable topography of the SLG substrates
      and remains intact after rinsing and drying the films. These results help to
      elucidate molecular behavior on SLG and suggest significant similarities between
      adsorption on HOPG and SLG. 

PMID- 25594563
TI  - A novel therapeutic effect of statins on nephrogenic diabetes insipidus.
AB  - Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase, resulting in reduced plasma total and low-density lipoprotein
      cholesterol levels. Recently, it has been shown that statins exert additional
      'pleiotropic' effects by increasing expression levels of the membrane water
      channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a
      critical role in determining cellular water content. This additional effect is
      independent of cholesterol homoeostasis, and depends on depletion of mevalonate
      derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate
      and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2,
      statins increase water reabsorption by the kidney, thus opening up a new avenue
      in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary
      disease that yet lacks high-powered and limited side effects therapy. Aspects
      related to water balance determined by AQP2 in the kidney, as well as standard
      and novel therapeutic strategies of NDI are discussed. 

PMID- 25594570
TI  - Jugular venous thrombosis secondary to idiopathic myelofibrosis: a rare cause of
      bilateral optic disc swelling.

PMID- 25594571
TI  - Absorption-improving effects of chitosan oligomers based on their mucoadhesive
      properties: a comparative study on the oral and pulmonary delivery of calcitonin.
AB  - Effects of chitosan oligomers with different types and varying concentrations on
      the intestinal and pulmonary absorptions of calcitonin were investigated in rats
      by an in situ closed loop method and an in vivo pulmonary absorption experiment,
      respectively. Various chitosan oligomers demonstrated different efficiencies in
      improving the intestinal and pulmonary absorptions of calcitonin, and chitosan
      hexamer with the optimal concentration of 0.5% (w/v) showed the greatest
      absorption enhancing effect. Moreover, pharmacodynamic parameters of calcitonin
      after its coadministration intrapulmonarily with various chitosan oligomers were
      consistently larger than that in the intestinal delivery, indicating the superior
      potential of pulmonary administration for systemic delivery of calcitonin.
      Furthermore, various chitosan oligomers neither obviously increased release
      amounts of protein nor activities of lactate dehydrogenase (LDH) in
      bronchoalveolar lavage fluid (BALF), revealing the safety of these chitosan
      oligomers to lung tissue. In addition, bioadhesions of various chitosan oligomers
      were well consistent with their absorption enhancing effects in the absorption
      experiment, suggesting the contribution of mucoadhesive properties of chitosan
      oligomers to their absorption improving effects. Taken together, chitosan
      oligomers, especially chitosan hexamer, can effectively improve the intestinal
      and pulmonary absorptions of calcitonin partly due to the mucoadhesion between
      positive chitosan oligomers and negative mucus in the membrane.

PMID- 25594572
TI  - Base deformation of full metal-jacketed rifle bullets as a measure of impact
      velocity and range of fire.
AB  - Full metal-jacketed rifle bullets with lead cores and open bases can experience
      deformation of their cylindrical shapes as they yaw during the penetration of
      soft tissues. The amount of deformation depends upon the strength of the bullet
      and the velocity in soft tissue when they go into yaw. The yaw behavior of a
      bullet in soft tissue depends upon its design (length, ogive shape, ogive length,
      center of gravity, and pre-impact stability) as it penetrates soft tissue. The
      yaw characteristics of common spitzer-type military rifle bullets are relatively
      well known and quite reproducible when fired into suitable soft tissue simulants.
      This, in turn, results in a relationship between the amount of deformation of the
      bullet's shank and impact velocity with soft tissue. The specific relationship
      between impact velocity and bullet deformation must be worked out through
      empirical testing, but this relationship can be of critical importance in
      determining impact velocity, which, in turn, relates to range of fire. 

PMID- 25594574
TI  - General strategy for computing nonlinear optical properties of large neutral and
      cationic organic chromophores in solution.
AB  - Tuning of nonlinear optical (NLO) properties of organic chromophores (OCs) by
      stereo-electronic and environmental effects has been widely documented by
      different experimental techniques and theoretical studies. Disentanglement and
      analysis of the different contributions requires, however, the availability of
      effective yet accurate quantum mechanical approaches for medium to large size
      systems in their natural environment. As a first step, we have shortly reviewed
      the phenomenological models still used by experimentalists to interpret their
      results and shown that a quantum mechanical approach based on the density
      functional theory (DFT) and the polarizable continuum model (PCM) should be able
      to overcome most theoretical limitations allowing, at the same time, the study of
      large systems with reasonable computational resources and the analysis of the
      results in terms of well-defined physical-chemical effects. After validation of
      the most suitable density functional/basis set in conjunction with the PCM
      description of bulk solvent effects, we have performed a systematic study of
      representative OCs, especially cationic ones, with special reference to their
      first order hyperpolarizability. The internal consistency of the results and
      their good agreement with experiment paves the route toward integrated
      experimental/computational studies of NLO properties taking together physical
      soundness, feasibility, reliability, and ease of interpretation. 

PMID- 25594573
TI  - Massively parallel neural circuits for stereoscopic color vision: encoding,
      decoding and identification.
AB  - Past work demonstrated how monochromatic visual stimuli could be faithfully
      encoded and decoded under Nyquist-type rate conditions. Color visual stimuli were
      then traditionally encoded and decoded in multiple separate monochromatic
      channels. The brain, however, appears to mix information about color channels at
      the earliest stages of the visual system, including the retina itself. If
      information about color is mixed and encoded by a common pool of neurons, how can
      colors be demixed and perceived? We present Color Video Time Encoding Machines
      (Color Video TEMs) for encoding color visual stimuli that take into account a
      variety of color representations within a single neural circuit. We then derive a
      Color Video Time Decoding Machine (Color Video TDM) algorithm for color demixing
      and reconstruction of color visual scenes from spikes produced by a population of
      visual neurons. In addition, we formulate Color Video Channel Identification
      Machines (Color Video CIMs) for functionally identifying color visual processing
      performed by a spiking neural circuit. Furthermore, we derive a duality between
      TDMs and CIMs that unifies the two and leads to a general theory of neural
      information representation for stereoscopic color vision. We provide examples
      demonstrating that a massively parallel color visual neural circuit can be first
      identified with arbitrary precision and its spike trains can be subsequently used
      to reconstruct the encoded stimuli. We argue that evaluation of the functional
      identification methodology can be effectively and intuitively performed in the
      stimulus space. In this space, a signal reconstructed from spike trains generated
      by the identified neural circuit can be compared to the original stimulus. 

PMID- 25594569
TI  - Perinatal oxygen in the developing lung.
AB  - Lung diseases, such as bronchopulmonary dysplasia (BPD), wheezing, and asthma,
      remain significant causes of morbidity and mortality in the pediatric population,
      particularly in the setting of premature birth. Pulmonary outcomes in these
      infants are highly influenced by perinatal exposures including prenatal
      inflammation, postnatal intensive care unit interventions, and environmental
      agents. Here, there is strong evidence that perinatal supplemental oxygen
      administration has significant effects on pulmonary development and health. This
      is of particular importance in the preterm lung, where premature exposure to room
      air represents a hyperoxic insult that may cause harm to a lung primed to develop
      in a hypoxic environment. Preterm infants are also subject to increased episodes
      of hypoxia, which may also result in pulmonary damage and disease. Here, we
      summarize the current understanding of the effects of oxygen on the developing
      lung and how low vs. high oxygen may predispose to pulmonary disease that may
      extend even into adulthood. Better understanding of the underlying mechanisms
      will help lead to improved care and outcomes in this vulnerable population. 

PMID- 25594575
TI  - Let it bleed.

PMID- 25594578
TI  - CdxPb(1-x)S alloy nanowires and heterostructures with simultaneous emission in
      mid-infrared and visible wavelengths.
AB  - Alloying of CdS and PbS could potentially provide an important semiconductor with
      a wide range of bandgaps, with bandedge emission from mid-infrared to visible
      green, for various optoelectronic applications. We investigate the possibility of
      CdPbS alloy formation in nanowire and nanobelt forms, especially the dependence
      of alloy composition on two different cooling routes. Our results show that rapid
      cooling immediately after the growth phase can lead to a high-quality uniform
      alloy with Cd composition larger than possible at thermal equilibrium and by
      natural cooling. On the contrary, unassisted natural cooling leads to the
      formation of axial or core-shell heterostructures, containing segments with pure
      CdS and CdPbS alloys with lower Cd content than through rapid cooling. Such
      heterostructures with green and mid-infrared emission provide simultaneous access
      to two widely separated wavelengths from a single monolithic structure and can be
      important for many applications. Our results can help identify strategies for
      growing nanostructures with uniform alloy of high Cd incorporation, core-shell
      structures with shell serving as a passivating or protecting layer, or
      interesting longitudinal heterostructures. Both various heterostructures and
      uniform alloys of these materials could be important for high-efficiency solar
      cells, novel detectors, and nanolasing in wide spectral ranges. 

PMID- 25594577
TI  - Ion exchange in hydroxyapatite with lanthanides.
AB  - Naturally occurring hydroxyapatite, Ca5(PO4)3(OH) (HAP), is the main inorganic
      component of bone matrix, with synthetic analogues finding applications in
      bioceramics and catalysis. An interesting and valuable property of both natural
      and synthetic HAP is the ability to undergo cationic and anionic substitution.
      The lanthanides are well-suited for substitution for the Ca(2+) sites within HAP,
      because of their similarities in ionic radii, donor atom requirements, and
      coordination geometries. We have used isothermal titration calorimetry (ITC) to
      investigate the thermodynamics of ion exchange in HAP with a representative
      series of lanthanide ions, La(3+), Sm(3+), Gd(3+), Ho(3+), Yb(3+) and Lu(3+),
      reporting the association constant (Ka), ion-exchange thermodynamic parameters
      (DeltaH, DeltaS, DeltaG), and binding stoichiometry (n). We also probe the nature
      of the La(3+):HAP interaction by solid-state nuclear magnetic resonance ((31)P
      NMR), X-ray diffraction (XRD), and inductively coupled plasma-optical emission
      spectroscopy (ICP-OES), in support of the ITC results. 

PMID- 25594576
TI  - An improved poly(A) motifs recognition method based on decision level fusion.
AB  - Polyadenylation is the process of addition of poly(A) tail to mRNA 3' ends.
      Identification of motifs controlling polyadenylation plays an essential role in
      improving genome annotation accuracy and better understanding of the mechanisms
      governing gene regulation. The bioinformatics methods used for poly(A) motifs
      recognition have demonstrated that information extracted from sequences
      surrounding the candidate motifs can differentiate true motifs from the false
      ones greatly. However, these methods depend on either domain features or string
      kernels. To date, methods combining information from different sources have not
      been found yet. Here, we proposed an improved poly(A) motifs recognition method
      by combing different sources based on decision level fusion. First of all, two
      novel prediction methods was proposed based on support vector machine (SVM): one
      method is achieved by using the domain-specific features and principle component
      analysis (PCA) method to eliminate the redundancy (PCA-SVM); the other method is
      based on Oligo string kernel (Oligo-SVM). Then we proposed a novel machine
      learning method for poly(A) motif prediction by marrying four poly(A) motifs
      recognition methods, including two state-of-the-art methods (Random Forest (RF)
      and HMM-SVM), and two novel proposed methods (PCA-SVM and Oligo-SVM). A decision
      level information fusion method was employed to combine the decision values of
      different classifiers by applying the DS evidence theory. We evaluated our method
      on a comprehensive poly(A) dataset that consists of 14,740 samples on 12 variants
      of poly(A) motifs and 2750 samples containing none of these motifs. Our method
      has achieved accuracy up to 86.13%. Compared with the four classifiers, our
      evidence theory based method reduces the average error rate by about 30%, 27%,
      26% and 16%, respectively. The experimental results suggest that the proposed
      method is more effective for poly(A) motif recognition. 

PMID- 25594579
TI  - Mass spectrometric approach for characterizing the disordered tail regions of the
      histone H2A/H2B dimer.
AB  - The histone H2A/H2B dimer is a component of nucleosome core particles (NCPs). The
      structure of the dimer at the atomic level has not yet been revealed. A possible
      reason for this is that the dimer has three intrinsically disordered tail
      regions: the N- and C-termini of H2A and the N-terminus of H2B. To investigate
      the role of the tail regions of the H2A/H2B dimer structure, we characterized
      behaviors of the H2A/H2B mutant dimers, in which these functionally important
      disordered regions were depleted, using mass spectrometry (MS). After verifying
      that the acetylation of Lys residues in the tail regions had little effect on the
      gas-phase conformations of the wild-type dimer, we prepared two histone H2A/H2B
      dimer mutants: an H2A/H2B dimer depleted of both N-termini (dN-H2A/dN-H2B) and a
      dimer with the N- and C-termini of H2A and the N-terminus of H2B depleted (dNC
      H2A/dN-H2B). We analyzed these mutants using ion mobility-mass spectrometry (IM
      MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS). With IM-MS,
      reduced structural diversity was observed for each of the tail-truncated H2A/H2B
      mutants. In addition, global HDX-MS proved that the dimer mutant dNC-H2A/dN-H2B
      was susceptible to deuteration, suggesting that its structure in solution was
      somewhat loosened. A partial relaxation of the mutant's structure was
      demonstrated also by IM-MS. In this study, we characterized the relationship
      between the tail lengths and the conformations of the H2A/H2B dimer in solution
      and gas phases, and demonstrated, using mass spectrometry, that disordered tail
      regions play an important role in stabilizing the conformation of the core region
      of the dimer in both phases. 

PMID- 25594580
TI  - Combined use of genetic and genomics resources to understand virus resistance and
      fruit quality traits in melon.
AB  - The availability of the genome sequence of many crop species during the past few
      years has opened a new era in plant biology, allowing for the performance of
      massive genomic studies in plant species other than the classical models
      Arabidopsis and rice. One of these crop species is melon (Cucumis melo), a
      cucurbit of high economic value that has become an interesting model for the
      study of biological processes such as fruit ripening, sex determination and
      phloem transport. The recent availability of the melon genome sequence, together
      with a number of genetic and genomic resources, provides powerful tools that can
      be used to assist in the main melon breeding targets, namely disease resistance
      and fruit quality. In this review, we will describe recent data obtained
      combining the use of a melon near isogenic line (NIL) population and genomic
      resources to gain insight into agronomically important traits as fruit ripening,
      resistance to Cucumber Mosaic virus (CMV) and the accumulation of sugars in
      fruits. 

PMID- 25594582
TI  - Evaluating Evidence Aid as a complex, multicomponent knowledge translation
      intervention.
AB  - Evidence Aid, an initiative established by members of The Cochrane Collaboration
      in the aftermath of the Indian Ocean Tsunami in December 2004, celebrates its
      first 10 years later this year. Whilst the principles of the Evidence Aid
      initiative are firmly rooted in evidence-based medicine and public health
      practice, the initiative itself was born of a humanitarian imperative, compassion
      and the expressed moral duty to help. The evidence-base for Evidence Aid, (that
      is, for knowledge translation interventions focused on dissemination of
      evidence), was not, and is not, well-established This article, which is based on
      a presentation at the Evidence Aid Symposium on 20 September 2014, at Hyderabad,
      India presents a unifying conceptual framework for use when researching the
      impact of Evidence Aid as a knowledge translation intervention. It highlights how
      each of the core activities can be mapped to this framework and identifies key
      outcomes of interest for evaluation. 

PMID- 25594583
TI  - Pushing the envelope in genetic analysis of species invasion.

PMID- 25594585
TI  - Synthesis of locked cyclohexene and cyclohexane nucleic acids (LCeNA and LCNA)
      with modified adenosine units.
AB  - We describe here the preparation of conformationally locked cyclohexane nucleic
      acids designed as hybrids between locked nucleic acids (LNAs) and cyclohexene
      nucleic acids (CeNAs), both of which excel in hybridization with complementary
      RNAs. We have accomplished the synthesis of these adenine derivatives starting
      from a simple ketoester and installed all four chiral centres by means of total
      synthesis. The acquired monomers were incorporated into nonamer oligonucleotides.

PMID- 25594586
TI  - Strategy to discover diverse optimal molecules in the small molecule universe.
AB  - The small molecule universe (SMU) is defined as a set of over 10(60)
      synthetically feasible organic molecules with molecular weight less than ~500 Da.
      Exhaustive enumerations and evaluation of all SMU molecules for the purpose of
      discovering favorable structures is impossible. We take a stochastic approach and
      extend the ACSESS framework ( Virshup et al. J. Am. Chem. Soc. 2013 , 135 , 7296 
      7303 ) to develop diversity oriented molecular libraries that can generate a set
      of compounds that is representative of the small molecule universe and that also
      biases the library toward favorable physical property values. We show that the
      approach is efficient compared to exhaustive enumeration and to existing
      evolutionary algorithms for generating such libraries by testing in the NKp
      fitness landscape model and in the fully enumerated GDB-9 chemical universe
      containing 3 * 10(5) molecules. 

PMID- 25594587
TI  - Stable emulsions prepared by self-assembly of hyaluronic acid and chitosan for
      papain loading.
AB  - A simple, green and effective process is developed to fabricate hyaluronic acid
      (HA)/chitosan (CS) complex colloidal particles through electrostatic
      interactions. The obtained complexes can be used as biocompatible emulsifiers and
      novel potential carriers for papain loading. An HA/CS mass ratio of 2 is the
      optimal condition leading to the smallest Dh (420.9 nm). The complexes with eight
      different mass ratios are used to stabilize white oil/water emulsions. The
      structure of the complexes at the oil-water interface varies in response to the
      mass ratio and can be classified into two typical structures, similar to typical
      polymeric surfactants and solid particulate emulsifiers. Furthermore, papain is
      introduced into the complex systems. Formation of the papain/HA/CS complexes in a
      compact form can protect the enzyme. Here, a novel strategy is introduced to
      fabricate a biocompatible emulsion from the HA/CS complexes and demonstrate that
      the stable complex is a suitable enzyme delivery system.

PMID- 25594584
TI  - Distinctive expression patterns of glycoprotein non-metastatic B and folliculin
      in renal tumors in patients with Birt-Hogg-Dube syndrome.
AB  - Birt-Hogg-Dube syndrome (BHD) is an inherited disorder associated with a germline
      mutation of the folliculin gene (FLCN). The affected families have a high risk
      for developing multiple renal cell carcinomas (RCC). Diagnostic markers that
      distinguish between FLCN-related RCC and sporadic RCC have not been investigated,
      and many patients with undiagnosed BHD fail to receive proper medical care. We
      investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were
      diagnosed by genetic testing. Possible somatic mutations of RCC lesions were
      investigated by DNA sequencing. Western blotting and immunohistochemical staining
      were used to compare the expression levels of FLCN and glycoprotein non
      metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n =
      62). The expression of GPNMB was also evaluated by quantitative RT-PCR.
      Histopathological analysis revealed that the most frequent histological type was
      chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6).
      Somatic mutation analysis revealed small intragenic mutations in six cases and
      loss of heterozygosity in two cases. Western blot and immunostaining analyses
      revealed that FLCN-related RCCs showed overexpression of GPNMB and
      underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB
      mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The
      distinctive expression patterns of GPNMB and FLCN might identify patients with
      RCCs who need further work-up for BHD.

PMID- 25594588
TI  - Kinect as a tool for gait analysis: validation of a real-time joint extraction
      algorithm working in side view.
AB  - The Microsoft Kinect sensor has gained attention as a tool for gait analysis for
      several years. Despite the many advantages the sensor provides, however, the lack
      of a native capability to extract joints from the side view of a human body still
      limits the adoption of the device to a number of relevant applications. This
      paper presents an algorithm to locate and estimate the trajectories of up to six
      joints extracted from the side depth view of a human body captured by the Kinect
      device. The algorithm is then applied to extract data that can be exploited to
      provide an objective score for the "Get Up and Go Test", which is typically
      adopted for gait analysis in rehabilitation fields. Starting from the depth-data
      stream provided by the Microsoft Kinect sensor, the proposed algorithm relies on
      anthropometric models only, to locate and identify the positions of the joints.
      Differently from machine learning approaches, this solution avoids complex
      computations, which usually require significant resources. The reliability of the
      information about the joint position output by the algorithm is evaluated by
      comparison to a marker-based system. Tests show that the trajectories extracted
      by the proposed algorithm adhere to the reference curves better than the ones
      obtained from the skeleton generated by the native applications provided within
      the Microsoft Kinect (Microsoft Corporation, Redmond,WA, USA, 2013) and OpenNI
      (OpenNI organization, Tel Aviv, Israel, 2013) Software Development Kits. 

PMID- 25594589
TI  - A robust linear feature-based procedure for automated registration of point
      clouds.
AB  - With the variety of measurement techniques available on the market today, fusing
      multi-source complementary information into one dataset is a matter of great
      interest. Target-based, point-based and feature-based methods are some of the
      approaches used to place data in a common reference frame by estimating its
      corresponding transformation parameters. This paper proposes a new linear feature
      based method to perform accurate registration of point clouds, either in 2D or
      3D. A two-step fast algorithm called Robust Line Matching and Registration
      (RLMR), which combines coarse and fine registration, was developed. The initial
      estimate is found from a triplet of conjugate line pairs, selected by a RANSAC
      algorithm. Then, this transformation is refined using an iterative optimization
      algorithm. Conjugates of linear features are identified with respect to a
      similarity metric representing a line-to-line distance. The efficiency and
      robustness to noise of the proposed method are evaluated and discussed. The
      algorithm is valid and ensures valuable results when pre-aligned point clouds
      with the same scale are used. The studies show that the matching accuracy is at
      least 99.5%. The transformation parameters are also estimated correctly. The
      error in rotation is better than 2.8% full scale, while the translation error is
      less than 12.7%. 

PMID- 25594590
TI  - Time-frequency feature representation using multi-resolution texture analysis and
      acoustic activity detector for real-life speech emotion recognition.
AB  - The classification of emotional speech is mostly considered in speech-related
      research on human-computer interaction (HCI). In this paper, the purpose is to
      present a novel feature extraction based on multi-resolutions texture image
      information (MRTII). The MRTII feature set is derived from multi-resolution
      texture analysis for characterization and classification of different emotions in
      a speech signal. The motivation is that we have to consider emotions have
      different intensity values in different frequency bands. In terms of human visual
      perceptual, the texture property on multi-resolution of emotional speech
      spectrogram should be a good feature set for emotion classification in speech.
      Furthermore, the multi-resolution analysis on texture can give a clearer
      discrimination between each emotion than uniform-resolution analysis on texture.
      In order to provide high accuracy of emotional discrimination especially in real
      life, an acoustic activity detection (AAD) algorithm must be applied into the
      MRTII-based feature extraction. Considering the presence of many blended emotions
      in real life, in this paper make use of two corpora of naturally-occurring
      dialogs recorded in real-life call centers. Compared with the traditional Mel
      scale Frequency Cepstral Coefficients (MFCC) and the state-of-the-art features,
      the MRTII features also can improve the correct classification rates of proposed
      systems among different language databases. Experimental results show that the
      proposed MRTII-based feature information inspired by human visual perception of
      the spectrogram image can provide significant classification for real-life
      emotional recognition in speech. 

PMID- 25594591
TI  - Chemical sensor platform for non-invasive monitoring of activity and dehydration.
AB  - A non-invasive solution for monitoring of the activity and dehydration of
      organisms is proposed in the work. For this purpose, a wireless standalone
      chemical sensor platform using two separate measurement techniques has been
      developed. The first approach for activity monitoring is based on humidity
      measurement. Our solution uses new humidity sensor based on a nanostructured TiO2
      surface for sweat rate monitoring. The second technique is based on monitoring of
      potassium concentration in urine. High level of potassium concentration denotes
      clear occurrence of dehydration. Furthermore, a Wireless Body Area Network (WBAN)
      was developed for this sensor platform to manage data transfer among devices and
      the internet. The WBAN coordinator controls the sensor devices and collects and
      stores the measured data. The collected data is particular to individuals and can
      be shared with physicians, emergency systems or athletes' coaches. Long-time
      monitoring of activity and potassium concentration in urine can help maintain the
      appropriate water intake of elderly people or athletes and to send warning
      signals in the case of near dehydration. The created sensor system was calibrated
      and tested in laboratory and real conditions as well. The measurement results are
      discussed. 

PMID- 25594592
TI  - Structure optimization of a grain impact piezoelectric sensor and its application
      for monitoring separation losses on tangential-axial combine harvesters.
AB  - Grain separation losses is a key parameter to weigh the performance of combine
      harvesters, and also a dominant factor for automatically adjusting their major
      working parameters. The traditional separation losses monitoring method mainly
      rely on manual efforts, which require a high labor intensity. With recent
      advancements in sensor technology, electronics and computational processing
      power, this paper presents an indirect method for monitoring grain separation
      losses in tangential-axial combine harvesters in real-time. Firstly, we developed
      a mathematical monitoring model based on detailed comparative data analysis of
      different feeding quantities. Then, we developed a grain impact piezoelectric
      sensor utilizing a YT-5 piezoelectric ceramic as the sensing element, and a
      signal process circuit designed according to differences in voltage amplitude and
      rise time of collision signals. To improve the sensor performance, theoretical
      analysis was performed from a structural vibration point of view, and the optimal
      sensor structural has been selected. Grain collide experiments have shown that
      the sensor performance was greatly improved. Finally, we installed the sensor on
      a tangential-longitudinal axial combine harvester, and grain separation losses
      monitoring experiments were carried out in North China, which results have shown
      that the monitoring method was feasible, and the biggest measurement relative
      error was 4.63% when harvesting rice. 

PMID- 25594593
TI  - An efficient distributed algorithm for constructing spanning trees in wireless
      sensor networks.
AB  - Monitoring and data collection are the two main functions in wireless sensor
      networks (WSNs). Collected data are generally transmitted via multihop
      communication to a special node, called the sink. While in a typical WSN, nodes
      have a sink node as the final destination for the data traffic, in an ad hoc
      network, nodes need to communicate with each other. For this reason, routing
      protocols for ad hoc networks are inefficient for WSNs. Trees, on the other hand,
      are classic routing structures explicitly or implicitly used in WSNs. In this
      work, we implement and evaluate distributed algorithms for constructing routing
      trees in WSNs described in the literature. After identifying the drawbacks and
      advantages of these algorithms, we propose a new algorithm for constructing
      spanning trees in WSNs. The performance of the proposed algorithm and the quality
      of the constructed tree were evaluated in different network scenarios. The
      results showed that the proposed algorithm is a more efficient solution.
      Furthermore, the algorithm provides multiple routes to the sensor nodes to be
      used as mechanisms for fault tolerance and load balancing. 

PMID- 25594594
TI  - Face liveness detection using defocus.
AB  - In order to develop security systems for identity authentication, face
      recognition (FR) technology has been applied. One of the main problems of
      applying FR technology is that the systems are especially vulnerable to attacks
      with spoofing faces (e.g., 2D pictures). To defend from these attacks and to
      enhance the reliability of FR systems, many anti-spoofing approaches have been
      recently developed. In this paper, we propose a method for face liveness
      detection using the effect of defocus. From two images sequentially taken at
      different focuses, three features, focus, power histogram and gradient location
      and orientation histogram (GLOH), are extracted. Afterwards, we detect forged
      faces through the feature-level fusion approach. For reliable performance
      verification, we develop two databases with a handheld digital camera and a
      webcam. The proposed method achieves a 3.29% half total error rate (HTER) at a
      given depth of field (DoF) and can be extended to camera-equipped devices, like
      smartphones. 

PMID- 25594596
TI  - Improving the lateral resolution of quartz tuning fork-based sensors in liquid by
      integrating commercial AFM tips into the fiber end.
AB  - The use of quartz tuning fork sensors as probes for scanning probe microscopy is
      growing in popularity. Working in shear mode, some methods achieve a lateral
      resolution comparable with that obtained with standard cantilevered probes, but
      only in experiments conducted in air or vacuum. Here, we report a method to
      produce and use commercial AFM tips in electrically driven quartz tuning fork
      sensors operating in shear mode in a liquid environment. The process is based on
      attaching a standard AFM tip to the end of a fiber probe which has previously
      been sharpened. Only the end of the probe is immersed in the buffer solution
      during imaging. The lateral resolution achieved is about 6 times higher than that
      of the etched microfiber on its own. 

PMID- 25594595
TI  - Functionalized solid electrodes for electrochemical biosensing of purine
      nucleobases and their analogues: a review.
AB  - Interest in electrochemical analysis of purine nucleobases and few other
      important purine derivatives has been growing rapidly. Over the period of the
      past decade, the design of electrochemical biosensors has been focused on
      achieving high sensitivity and efficiency. The range of existing electrochemical
      methods with carbon electrode displays the highest rate in the development of
      biosensors. Moreover, modification of electrode surfaces based on nanomaterials
      is frequently used due to their extraordinary conductivity and surface to volume
      ratio. Different strategies for modifying electrode surfaces facilitate electron
      transport between the electrode surface and biomolecules, including DNA,
      oligonucleotides and their components. This review aims to summarize recent
      developments in the electrochemical analysis of purine derivatives, as well as
      discuss different applications. 

PMID- 25594598
TI  - Ethanol microsensors with a readout circuit manufactured using the CMOS-MEMS
      technique.
AB  - The design and fabrication of an ethanol microsensor integrated with a readout
      circuit on-a-chip using the complementary metal oxide semiconductor (CMOS)
      microelectro -mechanical system (MEMS) technique are investigated. The ethanol
      sensor is made up of a heater, a sensitive film and interdigitated electrodes.
      The sensitive film is tin dioxide that is prepared by the sol-gel method. The
      heater is located under the interdigitated electrodes, and the sensitive film is
      coated on the interdigitated electrodes. The sensitive film needs a working
      temperature of 220  degrees C. The heater is employed to provide the working
      temperature of sensitive film. The sensor generates a change in capacitance when
      the sensitive film senses ethanol gas. A readout circuit is used to convert the
      capacitance variation of the sensor into the output frequency. Experiments show
      that the sensitivity of the ethanol sensor is 0.9 MHz/ppm. 

PMID- 25594597
TI  - Imaging of fluoride ion in living cells and tissues with a two-photon ratiometric
      fluorescence probe.
AB  - A reaction-based two-photon (TP) ratiometric fluorescence probe Z2 has been
      developed and successfully applied to detect and image fluoride ion in living
      cells and tissues. The Z2 probe was designed designed to utilize an ICT mechanism
      between n-butylnaphthalimide as a fluorophore and tert-butyldiphenylsilane
      (TBDPS) as a response group. Upon addition of fluoride ion, the Si-O bond in the
      Z2 would be cleaved, and then a stronger electron-donating group was released.
      The fluorescent changes at 450 and 540 nm, respectively, made it possible to
      achieve ratiometric fluorescence detection. The results indicated that the Z2
      could ratiometrically detect and image fluoride ion in living cells and tissues
      in a depth of 250 MUm by two-photon microscopy (TPM). 

PMID- 25594600
TI  - Optimal base station placement for wireless sensor networks with successive
      interference cancellation.
AB  - We consider the base station placement problem for wireless sensor networks with
      successive interference cancellation (SIC) to improve throughput. We build a
      mathematical model for SIC. Although this model cannot be solved directly, it
      enables us to identify a necessary condition for SIC on distances from sensor
      nodes to the base station. Based on this relationship, we propose to divide the
      feasible region of the base station into small pieces and choose a point within
      each piece for base station placement. The point with the largest throughput is
      identified as the solution. The complexity of this algorithm is polynomial.
      Simulation results show that this algorithm can achieve about 25% improvement
      compared with the case that the base station is placed at the center of the
      network coverage area when using SIC. 

PMID- 25594601
TI  - An X-band radar system for bathymetry and wave field analysis in a harbour area.
AB  - Marine X-band radar based systems are well tested to provide information about
      sea state and bathymetry. It is also well known that complex geometries and non
      uniform bathymetries provide a much bigger challenge than offshore scenarios. In
      order to tackle this issue a retrieval method is proposed, based on spatial
      partitioning of the data and the application of the Normalized Scalar Product
      (NSP), which is an innovative procedure for the joint estimation of bathymetry
      and surface currents. The strategy is then applied to radar data acquired around
      a harbour entrance, and results show that the reconstructed bathymetry compares
      well with ground truth data obtained by an echo-sounder campaign, thus proving
      the reliability of the whole procedure. The spectrum thus retrieved is then
      analysed to show the evidence of reflected waves from the harbour jetties, as
      confirmed by chain of hydrodynamic models of the sea wave field. The possibility
      of using a land based radar to reveal sea wave reflection is entirely new and may
      open up new operational applications of the system. 

PMID- 25594602
TI  - Trajectory-based visual localization in underwater surveying missions.
AB  - We present a new vision-based localization system applied to an autonomous
      underwater vehicle (AUV) with limited sensing and computation capabilities. The
      traditional EKF-SLAM approaches are usually expensive in terms of execution time;
      the approach presented in this paper strengthens this method by adopting a
      trajectory-based schema that reduces the computational requirements. The pose of
      the vehicle is estimated using an extended Kalman filter (EKF), which predicts
      the vehicle motion by means of a visual odometer and corrects these predictions
      using the data associations (loop closures) between the current frame and the
      previous ones. One of the most important steps in this procedure is the image
      registration method, as it reinforces the data association and, thus, makes it
      possible to close loops reliably. Since the use of standard EKFs entail
      linearization errors that can distort the vehicle pose estimations, the approach
      has also been tested using an iterated Kalman filter (IEKF). Experiments have
      been conducted using a real underwater vehicle in controlled scenarios and in
      shallow sea waters, showing an excellent performance with very small errors, both
      in the vehicle pose and in the overall trajectory estimates. 

PMID- 25594599
TI  - Design of surface modifications for nanoscale sensor applications.
AB  - Nanoscale biosensors provide the possibility to miniaturize optic, acoustic and
      electric sensors to the dimensions of biomolecules. This enables approaching
      single-molecule detection and new sensing modalities that probe molecular
      conformation. Nanoscale sensors are predominantly surface-based and label-free to
      exploit inherent advantages of physical phenomena allowing high sensitivity
      without distortive labeling. There are three main criteria to be optimized in the
      design of surface-based and label-free biosensors: (i) the biomolecules of
      interest must bind with high affinity and selectively to the sensitive area; (ii)
      the biomolecules must be efficiently transported from the bulk solution to the
      sensor; and (iii) the transducer concept must be sufficiently sensitive to detect
      low coverage of captured biomolecules within reasonable time scales. The majority
      of literature on nanoscale biosensors deals with the third criterion while
      implicitly assuming that solutions developed for macroscale biosensors to the
      first two, equally important, criteria are applicable also to nanoscale sensors.
      We focus on providing an introduction to and perspectives on the advanced
      concepts for surface functionalization of biosensors with nanosized sensor
      elements that have been developed over the past decades (criterion (iii)). We
      review in detail how patterning of molecular films designed to control
      interactions of biomolecules with nanoscale biosensor surfaces creates new
      possibilities as well as new challenges. 

PMID- 25594604
TI  - Polarizable density embedding: a new QM/QM/MM-based computational strategy.
AB  - We present a new QM/QM/MM-based model for calculating molecular properties and
      excited states of solute-solvent systems. We denote this new approach the
      polarizable density embedding (PDE) model, and it represents an extension of our
      previously developed polarizable embedding (PE) strategy. The PDE model is a
      focused computational approach in which a core region of the system studied is
      represented by a quantum-chemical method, whereas the environment is divided into
      two other regions: an inner and an outer region. Molecules belonging to the inner
      region are described by their exact densities, whereas molecules in the outer
      region are treated using a multipole expansion. In addition, all molecules in the
      environment are assigned distributed polarizabilities in order to account for
      induction effects. The joint effects of the inner and outer regions on the
      quantum-mechanical core part of the system is formulated using an embedding
      potential. The PDE model is illustrated for a set of dimers (interaction energy
      calculations) as well as for the calculation of electronic excitation energies,
      showing promising results. 

PMID- 25594603
TI  - Parameter evaluation and fully-automated radiosynthesis of [(11)C]harmine for
      imaging of MAO-A for clinical trials.
AB  - The aim of the present study was the evaluation and automation of the
      radiosynthesis of [(11)C]harmine for clinical trials. The following parameters
      have been investigated: amount of base, precursor concentration, solvent,
      reaction temperature and time. The optimum reaction conditions were determined to
      be 2-3mg/mL precursor activated with 1eq. 5M NaOH in DMSO, 80 degrees C reaction
      temperature and 2min reaction time. Under these conditions 6.1+/-1GBq (51.0+/-11%
      based on [(11)C]CH3I, corrected for decay) of [(11)C]harmine (n=72) were
      obtained. The specific activity was 101.32+/-28.2GBq/umol (at EOS). All quality
      control parameters were in accordance with the standards for parenteral human
      application. Due to its reliability and high yields, this fully-automated
      synthesis method can be used as routine set-up. 

PMID- 25594605
TI  - Polyfluorinated ethanes as versatile fluorinated C2-building blocks for organic
      synthesis.

PMID- 25594608
TI  - Towards Prospective Application of the UCM Method.

PMID- 25594606
TI  - Manganese and microbial pathogenesis: sequestration by the Mammalian immune
      system and utilization by microorganisms.
AB  - Bacterial and fungal pathogens cause a variety of infectious diseases and
      constitute a significant threat to public health. The human innate immune system
      represents the first line of defense against pathogenic microbes and employs a
      range of chemical artillery to combat these invaders. One important mechanism of
      innate immunity is the sequestration of metal ions that are essential nutrients.
      Manganese is one nutrient that is required for many pathogens to establish an
      infective lifestyle. This review summarizes recent advances in the role of
      manganese in the host-pathogen interaction and highlights Mn(II) sequestration by
      neutrophil calprotectin as well as how bacterial acquisition and utilization of
      manganese enables pathogenesis.

PMID- 25594607
TI  - In vivo evidence of neurophysiological maturation of the human adolescent
      striatum.
AB  - Maturation of the striatum has been posited to play a primary role in observed
      increases in adolescent sensation-seeking. However, evidence of
      neurophysiological maturation in the human adolescent striatum is limited. We
      applied T2*-weighted imaging, reflecting indices of tissue-iron concentration, to
      provide direct in vivo evidence of neurophysiological development of the human
      adolescent striatum. Multivariate pattern analysis (MVPA) of striatal T2*
      weighted signal generated age predictions that accounted for over 60% of the
      sample variance in 10-25 year olds, using both task-related and resting state
      fMRI. Dorsal and ventral striatum showed age related increases and decreases
      respectively of striatal neurophysiology suggesting qualitative differences in
      the maturation of limbic and executive striatal systems. In particular, the
      ventral striatum was found to show the greatest developmental differences and
      contribute most heavily to the multivariate age predictor. The relationship of
      the T2*-weighted signal to the striatal dopamine system is discussed. Together,
      results provide evidence for protracted maturation of the striatum through
      adolescence.

PMID- 25594610
TI  - Comparing the Effect of a Twice-weekly Tacrolimus and Betamethasone Valerate Dose
      on the Subclinical Epidermal Barrier Defect in Atopic Dermatitis.
AB  - The proactive use of topical anti-inflammatory (TAI) therapy to address
      subclinical inflammation is an effective, contemporary clinical strategy for the
      management of atopic dermatitis (AD). The interaction of a proactive TAI dose
      with the subclinical epidermal barrier defect in AD is yet to be determined. A
      randomised, observer-blind, functional mechanistic study in 17 subjects with
      quiescent AD was performed to compare the effect of a twice-weekly dose of
      betamethasone valerate (0.1%) cream (BMVc), against tacrolimus (0.1%) ointment
      (TACo) on the biophysical and biological properties of the epidermal barrier.
      Application of BMVc preserved epidermal barrier function and stratum corneum (SC)
      integrity, but significantly elevated skin-surface pH with concomitant loss of SC
      cohesion. By contrast, TACo improved SC integrity, exerted an overall hydrating
      action, and significantly reduced caseinolytic and trypsin-like protease
      activity. The differential effects reported support the proactive use of TACo to
      promote reparation of the subclinical barrier defect in AD.

PMID- 25594609
TI  - Glomerular filtration rate, urine production, and fractional clearance of
      electrolytes in acute kidney injury in dogs and their association with survival.
AB  - BACKGROUND: Acute kidney injury (AKI) is common in dogs. Few studies have
      assessed sequential changes in indices of kidney function in dogs with naturally
      occurring AKI. OBJECTIVE: To document sequential changes of conventional indices
      of renal function, to better define the course of AKI, and to identify a
      candidate marker for recovery. ANIMALS: Ten dogs with AKI. METHODS: Dogs were
      prospectively enrolled and divided into surviving and nonsurviving dogs. Urine
      production was measured with a closed system for 7 days. One and 24-hour urinary
      clearances were performed daily to estimate solute excretion and glomerular
      filtration rate (GFR). Solute excretion was calculated as an excretion ratio (ER)
      and fractional clearance (FC) based on both the 1- and 24-hour urine collections.
      RESULTS: Four dogs survived and 6 died. At presentation, GFR was not
      significantly different between the outcome groups, but significantly (P = .03)
      increased over time in the surviving, but not in the nonsurviving dogs.
      Fractional clearance of Na decreased significantly over time (20.2-9.4%, P <
      .0001) in the surviving, but not in the nonsurviving dogs. The ER and FC of
      solutes were highly correlated (r, 0.70-0.95). CONCLUSION AND CLINICAL IMPACT:
      Excretion ratio might be used in the clinical setting as a surrogate marker to
      follow trends in solute excretion. Increased GFR, urine production, and decreased
      FC of Na were markers of renal recovery. The FC of Na is a simple, noninvasive,
      and cost-effective method that can be used to evaluate recovery of renal
      function.

PMID- 25594611
TI  - Exploring the role of tanezumab as a novel treatment for the relief of
      neuropathic pain.
AB  - OBJECTIVE: Evaluate efficacy and safety of tanezumab, a humanized monoclonal
      antibody against nerve growth factor, in neuropathic pain. DESIGN: Two randomized
      controlled trials. SUBJECTS: Patients with pain due to diabetic peripheral
      neuropathy (DPN) or postherpetic neuralgia (PHN). METHODS: In the DPN study,
      patients received subcutaneous tanezumab 20 mg or placebo on Day 1 and Week 8.
      Evaluations included change from baseline in average DPN pain (primary endpoint),
      Patient's Global Assessment of DPN, and safety (including neuropathy
      assessments). Due to a partial clinical hold limiting enrollment and treatment
      duration, the prespecified landmark analysis was modified post hoc from Week 16
      to Week 8. In the PHN study, patients received intravenous tanezumab 50 MUg/kg,
      tanezumab 200 MUg/kg, or placebo on Day 1. Evaluations included change from
      baseline in average daily pain (primary endpoint), Brief Pain Inventory-short
      form, Patient's Global Assessment of pain from PHN, and safety. RESULTS: Mean DPN
      pain reduction from baseline to Week 8 was greater with tanezumab vs placebo (P =
      0.009); differences in Patient's Global Assessment of DPN were not significant (P
      > 0.05). Neither tanezumab dose resulted in significant differences vs placebo in
      efficacy in PHN (P > 0.05), although tanezumab 200 MUg/kg provided some benefit.
      Neuropathy assessments showed no meaningful changes. CONCLUSIONS: Tanezumab
      provided effective pain reduction in DPN. In PHN, only the highest tanezumab dose
      reduced pain; treatment differences were not significant. No new safety concerns
      were observed despite preexisting neuropathy.

PMID- 25594612
TI  - Human genetics of diabetic nephropathy.
AB  - Diabetic vascular complications (DVCs) affecting several important organ systems
      of human body such as cardiovascular system contribute a major public health
      problem. Genetic factors contribute to the risk of diabetic nephropathy (DN).
      Genetics variants, structural variants (copy number variation) and epigenetic
      changes play important roles in the development of DN. Apart from nucleus genome,
      mitochondrial DNA (mtDNA) plays critical roles in regulation of development of
      DN. Epigenetic studies have indicated epigenetic changes in chromatin affecting
      gene transcription in response to environmental stimuli, which provided a large
      body of evidence of regulating development of diabetes mellitus. This review
      focused on the current knowledge of the genetic and epigenetic basis of DN.
      Ultimately, identification of genes or genetic loci, structural variants and
      epigenetic changes contributed to risk or protection of DN will benefit
      uncovering the complex mechanism underlying DN, with crucial implications for the
      development of personalized medicine to diabetes mellitus and its complications.

PMID- 25594613
TI  - The importance of ultrasonographic measurement of peritoneal wall thickness in
      pediatric chronic peritoneal dialysis patients.
AB  - Loss of peritoneal function due to peritoneal fibrosing syndrome (PFS) is a major
      factor leading to treatment failure in chronic peritoneal dialysis (PD) patients.
      Although the precise biologic mechanisms responsible for these changes have not
      been defined, the general assumption is that alterations in peritoneal function
      are related to structural changes in the peritoneal membrane. Studies of the
      peritoneal membrane by non-invasive ultrasonography (US) in chronic PD patients
      are limited. The aim of the present study is to assess the relationship between
      functional parameters of peritoneum and peritoneal thickness measured by US in
      children treated by chronic PD. We recruited two groups of patients: 23 subjects
      (13 females, 10 males) on chronic PD (patient group) and 26 (7 females, 19 males)
      on predialysis out-patient follow-up (creatinine clearance: 20-60 mL/min/1.73
      m(2)) (control group). Age, sex, weight, height, body mass index (BMI), chronic
      PD duration, episodes of peritonitis and the results of peritoneal equilibration
      test (PET) were recorded. Hemoglobin (Hb), blood pressure (BP), left ventricular
      mass index (LVMI) and renal osteodystrophy (ROD) parameters were also obtained.
      The thickness of the parietal peritoneum was measured by trans-abdominal US in
      all children. Statistical analyses were performed by using Student's t and
      Pearson's correlation tests. Mean peritoneal thickness in chronic PD patients
      (1028.26 +/- 157.26 MUm) was significantly higher than control patients (786.52
      +/- 132.33). Mean peritoneal thickness was significantly correlated with mean
      body height (R(2) = 0.93, p < 0.05), BMI (R(2) = 0.25, p < 0.05), chronic PD
      duration (R(2) = 0.64, p < 0.05), episodes of peritonitis (R(2) = 0.93, p <
      0.05), D/Pcreatinine (R(2) = 0.76, p < 0.05) and D4/D0glucose (R(2) = 0.81, p <
      0.05). No correlation was found between peritoneal thickness and Hb, BP, LVMI and
      ROD parameters. In conclusion, ultrasonographic measurement of peritoneal
      membrane thickness is a simple and non-invasive method in chronic PD children.
      This diagnostic tool likely enables to assess peritoneal structure and function
      in these patients.

PMID- 25594614
TI  - The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity.
AB  - The polyphenol curcumin has several pharmacological effects, including
      antioxidant, anti-inflammatory and anti-cancer features. In this study, we
      evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats.
      Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7
      mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100 mg/kg via
      gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats
      exhibited kidney injury manifested by increased serum urea and creatinine
      (p<0.05). The kidney tissue from the cisplatin treated rats also exhibited a
      significant increase in the malondialdehyde (MDA) levels (p<0.05). The treatment
      with curcumin prevented a rise in the serum urea, creatinine and MDA levels when
      compared to the control group kidneys (p<0.05). The analysis the nicotinamide
      phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and
      SIRT4), which play important roles in the resistance to stress and the modulation
      of the threshold of cell death, showed similar trends (p<0.05). In the cisplatin
      only treated rats, the induced renal injury decreased the levels of the NAMPT and
      SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and
      SIRT proteins in the cisplatin-treated rats (p<0.05). These data suggest that
      curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity,
      thereby enhancing the therapeutic window of cisplatin.

PMID- 25594615
TI  - A 10-year follow-up of idiopathic membranous nephropathy patients on steroids and
      cyclophosphamide: a case series.
AB  - The studies of idiopathic membranous nephropathy (IMN) require sufficiently long
      duration of follow-up to understand the effect of treatment on the development of
      end-stage renal disease (ESRD) in IMN. The aim was to assess the remission rates
      with steroids and cyclophosphamide regimen for IMN at the end of 10 years of
      follow-up. A prospective, open-label study performed in Nephrology department of
      a state run tertiary care centre in a southern state of India. Adult (age >18
      years) patients with biopsy-proven IMN of at least 6-month duration were included
      in the study. Patients received a 6-month course of alternate months of steroid
      and cyclophosphamide. The patients were followed for 10 years. Study end points
      were doubling of serum creatinine, development of ESRD, or death. A total of 58
      IMN patients were recruited from 1997 to 2001. Out of 58 patients included, only
      48 patients could complete the treatment schedule in six months. The remission
      rate at the end of 10 years was 58.6% (34 in 58 patients). The probability of
      dialysis-free survival in our study was 89.6% at the end of 10 years follow-up.
      The regimen of steroids and cyclophosphamide in IMN had a remission rates not as
      high as reported before. It was associated with high relapse rates and more
      infections. 

PMID- 25594616
TI  - Concise review: induced pluripotency by defined factors: prey of oxidative
      stress.
AB  - Reprogramming somatic cells to pluripotency (induced pluripotent stem cells,
      iPSCs) via forced expression of defined factors has become one of the most
      fascinating areas in biomedical research because it holds a tremendous
      application potential for cell therapy, disease modeling, and drug screening
      applications. However, cellular reprogramming is a very inefficient and
      metabolically demanding process commonly associated with genomic instability of
      the resulting iPSCs. Low reprogramming efficiency and presence of de novo genomic
      aberrations in iPSCs may hamper their downstream applications. Here, we review
      mounting studies that have tackled reprogramming efficiency and genome stability
      of iPSCs. In particular, we focus on the effect of oxidative stress on cellular
      reprogramming. We will discuss how oxidative stress influences cellular
      reprogramming and the mechanisms by which antioxidants promote reprogramming
      efficiency and preserve genome integrity of iPSCs. A reduction of oxidative
      stress is expected to augment reprogramming efficiency and concomitantly promote
      the genomic integrity of the resulting iPSCs, eventually facilitating the
      implementation of cellular reprogramming for downstream applications. Stem Cells
      2015;33:1371-1376. 

PMID- 25594617
TI  - Noradrenaline enhances angiotensin II responses via p38 MAPK activation after
      hypoxia/re-oxygenation in renal interlobar arteries.
AB  - AIM: Hypoxia and sympathetic activation are main factors in the pathogenesis of
      acute kidney injury (AKI). We tested the hypothesis that noradrenaline (NE) in
      combination with hypoxia aggravates the vasoreactivity of renal arteries after
      hypoxia/re-oxygenation (H/R). We tested the role of adrenergic receptors and p38
      MAPK using an in vitro H/R protocol. METHODS: Mouse interlobar arteries (ILA) and
      afferent arterioles (AA) were investigated under isometric and isotonic
      conditions respectively. The in vitro protocol consisted of 60-min hypoxia and
      control condition, respectively, 10-min re-oxygenation followed by concentration
      response curves for Ang II or endothelin. RESULTS: Hypoxia reduced the response
      to Ang II. Hypoxia and NE (10(-9)  mol L(-1) ) together increased it in ILA and
      AA. In ILA, NE alone influenced neither Ang II responses under control conditions
      nor endothelin responses after hypoxia. Prazosin or yohimbine treatment did not
      significantly influence the NE+hypoxia effect. The combination of prazosin and
      yohimbine or propranolol alone inhibited the effect of NE+hypoxia. BRL37344
      (beta3 receptor agonist) mimicked the NE effect. In contrast, the incubation with
      beta3 receptor blocker did not influence the mentioned effect. Phosphorylation of
      p38 MAPK and MLC(20) was increased after H/R with NE and Ang II treatment. The
      selective p38 MAPK inhibitor SB202190 blocked the NE+hypoxia effect on the Ang II
      response. CONCLUSION: The results suggest an interaction of NE and hypoxia in
      enhancing vasoreactivity, which may be important for the pathogenesis of AKI. The
      effect of NE+hypoxia in ILA is mediated by several adrenergic receptors and
      requires the p38 MAPK activation.

PMID- 25594618
TI  - Polymorphisms and haplotypes of the TGF-beta1 gene are associated with risk of
      polycystic ovary syndrome in Chinese Han women.
AB  - OBJECTIVES: Transforming growth factor-beta 1 (TGF-beta1) is one of the
      multifunctional cytokine families. It takes part in a series of physiological and
      pathological processes in the human body, including wound healing, tissue
      fibrosis and embryonic development. Recent studies have shown that TGF-beta1
      participates in the development of polycystic ovary syndrome (PCOS). This study
      was therefore designed to investigate the association of TGF-beta1 polymorphism
      with the risk of PCOS. STUDY DESIGN: We enrolled 328 PCOS patients and 358
      healthy individuals in this study. Five single nucleotide polymorphisms (SNPs) -
      rs4803457C/T, rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and
      rs1800470C/T - were detected using Snapshot technology. Linkage disequilibrium
      and haplotype analysis was conducted among the five SNPs. The relationship
      between genotypes and haplotypes and the risk of PCOS was also explored. RESULTS:
      The TT/CT/CC genotype frequencies of rs4803457 in the PCOS group and the control
      group were 0.2805/0.4878/0.2317 and 0.3659/0.4749/0.1592 respectively. The C/T
      allele frequencies in the PCOS group and control group were 0.3813/0.6187 and
      0.3966/0.6034 respectively. There were significant differences in genotype
      distribution frequencies and allele frequencies between these two groups
      (P=0.018). Logistic regression analysis showed that CC genotype had higher risk
      of PCOS than the no CC genotype in rs4803457 loci (OR=1.75, 95%CI=1.11-2.75).
      Haplotype analysis further showed that the haplotypes "T-del-C-C-C", "C-del-C-C
      C" and "C-del-C-T-C" were associated with the highest risk of PCOS. However, for
      rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T, no
      significant association with PCOS risk was observed. CONCLUSION: The TGF-beta1
      gene rs4803457C/T polymorphism is associated with susceptibility to PCOS, and is
      the key contributor for the development of PCOS in Chinese Han women. The
      haplotypes T-del-C-C-C, C-del-C-C-C and C-del-C-T-C are also risk factors for
      PCOS susceptibility among Chinese Han women.

PMID- 25594619
TI  - In vitro metabolism of the lignan (-)-grandisin, an anticancer drug candidate, by
      human liver microsomes.
AB  - (-)-grandisin is a tetrahydrofuran lignan that displays important biological
      properties, such as trypanocidal, anti-inflammatory, cytotoxic, and antitumor
      activities, suggesting its utility as a potential drug candidate. One important
      step in drug development is metabolic characterization and metabolite
      identification. To perform a biotransformation study of (-)-grandisin and to
      determine its kinetic properties in humans, a high performance liquid
      chromatography (HPLC) method was developed and validated. After HPLC method
      validation, the kinetic properties of (-)-grandisin were determined. (-)
      grandisin metabolism obeyed Michaelis-Menten kinetics. The maximal reaction rate
      (Vmax ) was 3.96 +/- 0.18 umol/mg protein/h, and the Michaelis-Menten constant
      (Km ) was 8.23 +/- 0.99 MUM. In addition, the structures of the metabolites
      derived from (-)-grandisin were characterized via gas chromatography-mass
      spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)
      analysis. Four metabolites, 4-O-demethylgrandisin, 3-O-demethylgrandisin, 4,4'-di
      O-demethylgrandisin, and a metabolite that may correspond to either 3,4-di-O
      demethylgrandisin or 3,5-di-O-demethylgrandisin, were detected. CYP2C9 isoform
      was the main responsible for the formation of the metabolites. These metabolites
      have not been previously described, demonstrating the necessity of assessing (-)
      grandisin metabolism using human-derived materials.

PMID- 25594620
TI  - Uterine artery pulsatility index in the three trimesters of pregnancy: effects of
      maternal characteristics and medical history.
AB  - OBJECTIVE: To define the contribution of maternal variables that influence the
      measured uterine artery pulsatility index (UtA-PI) in screening for pregnancy
      complications. METHODS: Maternal characteristics and medical history were
      recorded, and UtA-PI was measured, in women with a singleton pregnancy attending
      for three routine hospital visits at 11 + 0 to 13 + 6 weeks, 19 + 0 to 24 + 6
      weeks and 30 + 0 to 34 + 6 weeks or 35 + 0 to 37 + 6 weeks' gestation. For
      pregnancies delivering phenotypically normal live births or stillbirths at >= 24
      weeks' gestation, variables from maternal demographic characteristics and medical
      history that are important in the prediction of UtA-PI were determined from
      linear mixed-effects multiple regression. RESULTS: UtA-PI was measured in 90 484
      cases in the first trimester, 66 862 cases in the second trimester and 33 470
      cases in the third trimester of pregnancy. Significant independent contributions
      to UtA-PI were provided by gestational age, maternal age, weight, racial origin
      and a history of pre-eclampsia (PE) in the previous pregnancy. Random-effects
      multiple regression analysis was used to define the contribution of maternal
      variables that influence the measured UtA-PI and express the values as multiples
      of the median (MoM). The model was shown to provide an adequate fit of MoM values
      for all covariates both in pregnancies that developed PE and in those that did
      not. CONCLUSIONS: A model was fitted to express the measured UtA-PI as MoMs after
      adjustment for variables from maternal characteristics and medical history that
      affect this measurement.

PMID- 25594621
TI  - A critique of why looks can be deceptive in judging the health of well-fed corals
      (related to DOI 10.1002/bies.201400074).

PMID- 25594623
TI  - Recent advances in primary cutaneous T-cell lymphoma.
AB  - PURPOSE OF REVIEW: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of
      skin-homing T-cell neoplasms, which represent approximately 75% of all primary
      cutaneous lymphomas. Currently available drug therapies, when effective, simply
      control disease and the only option for curing CTCL is stem cell transplant.
      RECENT FINDINGS: In the last year, there has been an incredible effort made to
      improve the understanding and treatment of CTCL. Recent findings indicate that
      epigenetic aberrations are integral to active disease. Furthermore, multiple
      tumor-derived immunological factors have also been shown to inhibit viability,
      proliferation, and cytokine production of nonmalignant T cells. Several novel
      targeted therapies show great potential, most promising being antibody drug
      conjugates targeting surface markers such as CD30 in some CTCL subtypes.
      Additional attractive targets involve the global modulation of epigenetic markers
      such as demethylation agents or HDAC inhibitors, either as single agents or in
      combination therapies. SUMMARY: This is a concise review of recent advances in
      the field of CTCL with special focus on research articles over the preceding
      year.

PMID- 25594624
TI  - Identification and analysis of a novel bmp4 enhancer in Fugu genome.
AB  - Spatiotemporal expression of bone morphogenetic protein 4 (Bmp4) in epithelial
      and mesenchymal cells is critical for the development of many organs including
      teeth. Since Bmp4 has a complex and widespread regulatory area in mammals, the
      tissue-specific enhancers that are responsible for mesenchymal expression of Bmp4
      are difficult to identify in mammals. TakiFugu rubripes (Fugu, pufferfish) has a
      highly compact genome size and is widely used in comparative genomics studies of
      gene regulatory mechanisms. In this study, we used the Fugu genome to evaluate
      the 15kb promoter region upstream of the Fugu bmp4 gene. By DNA segmental cloning
      and luciferase assay with two dental odontoblast-like cell lines, a dental
      ameloblast-like cell line, and a kidney fibroblast cell line, we identified a
      485bp cis-regulatory enhancer between -4213 and -3728bp of the Fugu bmp4 gene.
      This enhancer showed strong transcriptional activity in all three dental cell
      lines and, to a lesser extent, also in kidney fibroblast cells. Though not
      located in an evolutionary conserved region, the enhancer activity for the DNA
      segment is intense. This is the first time a bmp4 enhancer sequence with activity
      in both mesenchymal and epithelial cells has been identified, which will help to
      decode the mechanism of tooth development in vertebrates. 

PMID- 25594625
TI  - Fiber-optic sensors for monitoring patient physiological parameters: a review of
      applicable technologies and relevance to use during magnetic resonance imaging
      procedures.
AB  - The issues involved with recording vital functions in the magnetic resonance
      imaging (MRI) environment using fiber-optic sensors are considered in this paper.
      Basic physiological parameters, such as respiration and heart rate, are
      fundamental for predicting the risk of anxiety, panic, and claustrophobic
      episodes in patients undergoing MRI examinations. Electronic transducers are
      generally hazardous to the patient and are prone to erroneous operation in
      heavily electromagnetically penetrated MRI environments; however, nonmetallic
      fiber-optic sensors are inherently immune to electromagnetic effects and will be
      crucial for acquiring the above-mentioned physiological parameters. Forty-seven
      MRI-tested or potentially MRI-compatible sensors have appeared in the literature
      over the last 20 years. The author classifies these sensors into several
      categories and subcategories, depending on the sensing element placement, method
      of application, and measure and type. The author includes five in-house-designed
      fiber Bragg grating based sensors and shares experience in acquiring
      physiological measurements during MRI scans. This paper aims to systematize the
      knowledge of fiber-optic techniques for recording life functions and to indicate
      the current directions of development in this area.

PMID- 25594626
TI  - Integrated flexible handheld probe for imaging and evaluation of iridocorneal
      angle.
AB  - An imaging probe is designed and developed by integrating a miniaturized charge
      coupled diode camera and light-emitting diode light source, which enables
      evaluation of the iridocorneal region inside the eye. The efficiency of the
      prototype probe instrument is illustrated initially by using not only eye models,
      but also samples such as pig eye. The proposed methodology and developed scheme
      are expected to find potential application in iridocorneal angle documentation,
      glaucoma diagnosis, and follow-up management procedures.

PMID- 25594627
TI  - Optical coherence tomography based microangiography for quantitative monitoring
      of structural and vascular changes in a rat model of acute uveitis in vivo: a
      preliminary study.
AB  - Uveitis models in rodents are important in the investigation of pathogenesis in
      human uveitis and the development of appropriate therapeutic strategies for
      treatment. Quantitative monitoring of ocular inflammation in small animal models
      provides an objective metric to assess uveitis progression and/or therapeutic
      effects. We present a new application of optical coherence tomography (OCT) and
      OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis
      induced by intravitreal injection of a killed mycobacterial extract. OCT/OMAG is
      used to provide noninvasive three-dimensional imaging of the anterior segment of
      the eyes prior to injection (baseline) and two days post-injection (peak
      inflammation) in rats with and without steroid treatments. OCT imaging identifies
      characteristic structural and vascular changes in the anterior segment of the
      inflamed animals when compared to baseline images. Characteristics of
      inflammation identified include anterior chamber cells, corneal edema, pupillary
      membranes, and iris vasodilation. In contrast, no significant difference from the
      control is observed for the steroid-treated eye. These findings are compared with
      the histology assessment of the same eyes. In addition, quantitative measurements
      of central corneal thickness and iris vessel diameter are determined. This pilot
      study demonstrates that OCT-based microangiography promises to be a useful tool
      for the assessment and management of uveitis in vivo.

PMID- 25594629
TI  - Investigation of the cortical activation by touching fabric actively using
      fingers.
AB  - BACKGROUND/PURPOSE: Human subjects can tactually estimate the perception of
      touching fabric. Although many psychophysical and neurophysiological experiments
      have elucidated the peripheral neural mechanisms that underlie fabric hand
      estimation, the associated cortical mechanisms are not well understood. METHODS:
      To identify the brain regions responsible for the tactile stimulation of fabric
      against human skin, we used the technology of functional magnetic resonance
      imaging (fMRI), to observe brain activation when the subjects touched silk fabric
      actively using fingers. RESULTS: Consistent with previous research about brain
      cognition on sensory stimulation, large activation in the primary somatosensory
      cortex (SI), the secondary somatosensory cortex (SII) and moto cortex, and little
      activation in the posterior insula cortex and Broca's Area were observed when the
      subjects touched silk fabric. CONCLUSION: The technology of fMRI is a promising
      tool to observe and characterize the brain cognition on the tactile stimulation
      of fabric quantitatively. The intensity and extent of activation in the brain
      regions, especially the primary somatosensory cortex (SI) and the secondary
      somatosensory cortex (SII), can represent the perception of stimulation of fabric
      quantitatively.

PMID- 25594630
TI  - Electrolyte-assisted electrospinning for a self-assembled, free-standing
      nanofiber membrane on a curved surface.
AB  - A free-standing nanofiber membrane can be simultaneously fabricated, patterned,
      and integrated with electrolyte-assisted electrospinning (ELES). The fluidic
      nature of the electrolyte collector enables flexible patterning and facile
      integration of the free-standing nanofiber membrane on complex substrates from a
      2D flat surface to a 3D curved geometry via ELES. The structural integrity and
      performance of the free-standing nanofiber membrane are verified, and this plays
      a crucial role for future applications, including organ-on-a-chip, tissue
      scaffolds, and biosensors. 

PMID- 25594628
TI  - Lactate: brain fuel in human traumatic brain injury: a comparison with normal
      healthy control subjects.
AB  - We evaluated the hypothesis that lactate shuttling helps support the nutritive
      needs of injured brains. To that end, we utilized dual isotope tracer [6,6
      (2)H2]glucose, that is, D2-glucose, and [3-(13)C]lactate techniques involving arm
      vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular
      bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with
      nonpenetrating brain injuries (n=12) were entered into the study following
      consent of patients' legal representatives. Written and informed consent was
      obtained from control volunteers (n=6). Patients were studied 5.7+/-2.2 (mean+/
      SD) days post-injury; during periods when arterial glucose concentration tended
      to be higher in TBI patients. As in previous investigations, the cerebral
      metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly
      suppressed following TBI (p<0.001). However, lactate fractional extraction, an
      index of cerebral lactate uptake related to systemic lactate supply, approximated
      11% in both healthy control subjects and TBI patients. Further, neither the CMR
      for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral
      lactate uptake differed between healthy controls and TBI patients. The
      percentages of lactate tracer taken up and released as (13)CO2 into the JB
      accounted for 92% and 91% for control and TBI conditions, respectively,
      suggesting that most cerebral lactate uptake was oxidized following TBI.
      Comparisons of isotopic enrichments of lactate oxidation from infused [3
      (13)C]lactate tracer and (13)C-glucose produced during hepatic and renal
      gluconeogenesis (GNG) showed that 75-80% of (13)CO2 released into the JB was from
      lactate and that the remainder was from the oxidation of glucose secondarily
      labeled from lactate. Hence, either directly as lactate uptake, or indirectly via
      GNG, peripheral lactate production accounted for ~70% of carbohydrate (direct
      lactate uptake+uptake of glucose from lactate) consumed by the injured brain.
      Undiminished cerebral lactate fractional extraction and uptake suggest that
      arterial lactate supplementation may be used to compensate for decreased CMRgluc
      following TBI. 

PMID- 25594632
TI  - Taking stock.

PMID- 25594631
TI  - Protein dynamics in the solid state from 2H NMR line shape analysis: a consistent
      perspective.
AB  - Deuterium line shape analysis of CD3 groups has emerged as a particularly useful
      tool for studying microsecond-millisecond protein motions in the solid state. The
      models devised so far consist of several independently conceived simple jump-type
      motions. They are comprised of physical quantities encoded in their simplest
      form; improvements are only possible by adding yet another simple motion, thereby
      changing the model. The various treatments developed are case-specific; hence
      comparison among the different systems is not possible. Here we develop a new
      methodology for (2)H NMR line shape analysis free of these limitations. It is
      based on the microscopic-order-macroscopic-disorder (MOMD) approach. In MOMD
      motions are described by diffusion tensors, spatial restrictions by
      potentials/ordering tensors, and geometric features by relative tensor
      orientations. Jump-type motions are recovered in the limit of large orientational
      potentials. Model improvement is accomplished by monitoring the magnitude,
      symmetry, and orientation of the various tensors. The generality of MOMD makes
      possible comparison among different scenarios. CD3 line shapes from the Chicken
      Villin Headpiece Subdomain and the Streptomyces Subtilisin Inhibitor are used as
      experimental examples. All of these spectra are reproduced by using rhombic local
      potentials constrained for simplicity to be given by the L = 2 spherical
      harmonics, and by axial diffusion tensors. Potential strength and rhombicity are
      found to be ca. 2-3 k(B)T. The diffusion tensor is tilted at 120 degrees  from
      the C-CD3 axis. The perpendicular (parallel) correlation times for local motion
      are 0.1-1.0 ms (3.3-30 MUs). Activation energies in the 1.1-8.0 kcal/mol range
      are estimated. Future prospects include extension to the (2)H relaxation limit,
      application to the (15)N and (13)C NMR nuclei, and accounting for collective
      motions and anisotropic media.

PMID- 25594633
TI  - A giant lymphatic cyst of the adrenal gland: report of a rare case and review of
      the literature.
AB  - Lymphatic type of adrenal cysts is most common; however, this type of endothelial
      cyst is quite rare in excessively large adrenal cysts. A 37-year-old Japanese
      woman was admitted to our institution with distension of her left flank and the
      upper quadrant of her abdomen. Abdominal ultrasonography revealed a cystic lesion
      with a homogenous anechoic texture, and measuring 21 cm in diameter. Computed
      tomography and magnetic resonance imaging displayed a giant cystic lesion
      adjacent to the liver, pancreas, kidney, and spleen. The origin of the cyst was
      not identified. We were not able to make a preoperative diagnosis; therefore, the
      patient underwent resection of the mass by open laparotomy for therapeutic
      diagnosis. Intraoperatively, the mass was identified to be cystic and adhered to
      the left adrenal gland. It was filled with more than 2000 mL of serous brown-red
      fluid. The content of the cyst contained no atypical cells on cytological
      examination. The wall of the cyst was composed of a lining of a single layer of
      lymphatic vessel-derived cells, and the cyst was pathologically classified as a
      true cyst. No abdominal symptoms were observed and a postoperative radiological
      work-up showed no evidence of recurrence during a 6-year follow-up period. We
      describe a case of a patient with a giant lymphatic cyst of the adrenal gland.
      The preset data suggest that surgeons should decide treatment strategy for large
      adrenal cysts in consideration of hormonal function, degree of size, and
      possibility of malignancy. 

PMID- 25594635
TI  - Single-incision plus one-port laparoscopic abdominoperineal resection with
      bilateral pelvic lymph node dissection for advanced rectal cancer: a case report.
AB  - With regard to laparoscopic and robotic abdominoperineal resection (APR) for
      primary rectal malignancies, limited data have been published in the literature.
      Single-incision laparoscopic surgery (SLS) has been successfully introduced for
      treating colorectal cancer. Here we describe our experience of APR with SLS plus
      one port (SLS + 1) for treating advanced rectal cancer. A 65-year-old man
      underwent the procedure, which involved a 35-mm incision in the left side of the
      umbilicus for the insertion of a single multichannel port as well as the
      insertion of a 5-mm port into the right lower quadrant. The sigmoid colon and
      rectum were mobilized from the pelvic floor using a medial and lateral approach.
      After the rectum with the mesorectum was completely mobilized according to the
      total mesorectal excision, the sigmoid colon was intracorporeally transected. The
      specimen was removed through the perineal wound. Terminal colostomy was fashioned
      at the left lower trocar site. Lateral pelvic lymph node dissection was
      bilaterally performed. There were no perioperative complications. The total
      operating time was 592 minutes, and the estimated blood loss was 180 mL. To our
      knowledge, this is the first reported case of SLS + 1 APR with lateral pelvic
      lymph node dissection for treating rectal cancer. We conclude that SLS + 1 APR is
      a technically promising alternative method for treating selected patients with
      advanced rectal cancer. 

PMID- 25594634
TI  - Should subtotal thyroidectomy be abandoned in multinodular goiter patients from
      endemic regions requiring surgery?
AB  - The most convenient surgical procedure for benign thyroid diseases is still
      controversial. The aim of this study is to determine the recurrence rate and risk
      factors for recurrence after different thyroidectomy procedures in multinodular
      goiter patients. Patients were separated into two groups according to the
      detection of a recurrent nodule or not after thyroidectomy. Of the 748 patients,
      216 (29%) had recurrence, while 532 had no recurrent nodule. The difference
      between surgical procedures described as subtotal (ST), near total (NT) and total
      thyroidectomy (TT) was statistically significant. Transient hypoparathyroidism
      was significantly higher in NT and TT, when compared to ST patients (P < 0.05).
      Young age, bilateral multinodular goiter and insufficient surgery are risk
      factors affecting recurrence for benign nodular thyroid disease. Currently,
      subtotal procedures should be discontinued and total or near total procedures
      should be preferred. Meanwhile, the probability of a higher risk of
      hypoparathyroidism should be kept in mind. 

PMID- 25594636
TI  - Cytoreductive surgery and heated intraperitoneal chemotherapy for peritoneal
      carcinomatosis secondary to mucinous adenocarcinoma of the appendix.
AB  - Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy
      (HIPEC) is a radical but effective treatment option for select peritoneal
      malignancies. We sought to determine our early experience with this method for
      peritoneal carcinomatosis secondary to mucinous adenocarcinomas of appendiceal
      origin. As such, we performed a retrospective clinical study of 30 consecutive
      patients undergoing CRS with planned HIPEC at the Princess Alexandra Hospital,
      between June 2009 to December 2012, with mucinous adenocarcinomas of the
      appendix. CRS was performed in 30 patients, 13 received HIPEC intraoperatively
      and 17 received early postoperative intra-peritoneal chemotherapy (EPIC) in
      addition. Mean age was 52.3 years and median hospital stay was 26 days (range 12
      190 days). Peritoneal cancer index scores were 0-10 in 6.7% of patients, 11-20 in
      20% of patients and >20 in 73.3% of patients. Complete cytoreduction was achieved
      overall in 21 patients. In total, 106 complications were observed in 28 patients.
      Ten were grade 3-A, five were grade 3-B and one grade-5 secondary to a fatal PE
      on day 97. In patients who received HIPEC, there was no difference in disease
      free survival (P = 0.098) or overall survival (P = 0.645) between those who
      received EPIC versus those who did not. This study demonstrates that satisfactory
      outcomes with regards to morbidity and survival can be achieved with CRS and
      HIPEC, at a single-centre institution with growing expertise in the technique.
      Our results are comparable with outcomes previously described in the
      international literature. 

PMID- 25594637
TI  - Fecoflowmetric analysis of anorectal motor function in postoperative anal
      preserving surgery patients with low rectal cancer comparison with the wexner
      score and anorectal manometry.
AB  - The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate
      more detailed evacuative function than anorectal manometry by comparing between
      FFM or anorectal manometric findings and the clinical questionnaires and the
      types of surgical procedure in the patients who received anal-preserving surgery.
      Fifty-three patients who underwent anal-preserving surgery for low rectal cancer
      were enrolled. The relationships between FFM or the manometric findings and the
      clinical questionnaires and the types of procedure of anal-preserving surgery
      were evaluated. There were significant differences between FFM markers and the
      clinical questionnaire and the types of the surgical procedure, whereas no
      significant relationship was observed between the manometric findings and the
      clinical questionnaire and the types of the surgical procedure. FFM might be
      feasible and useful for the objective assessment of evacuative function and may
      be superior to manometry for patients undergoing anal-preserving surgery. 

PMID- 25594638
TI  - Plasma osteopontin predicts inflammatory bowel disease activities.
AB  - A glycoprotein osteopontin (OPN) is involved in inflammatory diseases, but its
      roles in inflammatory bowel disease (IBD) are controversial. To analyze the
      involvement of the systemic immune response, we simultaneously examined plasma
      OPN levels and 17 cytokines. This study included 24 ulcerative colitis (UC)
      patients, 17 Crohn's disease (CD) patients, and 23 normal controls. Clinical
      parameters were also examined. The plasma OPN levels of the UC and CD patients
      were significantly higher than those of the normal controls and correlated
      significantly with their clinical activity indices. In the UC patients,
      significant relationships were observed between the levels of plasma OPN and
      multiple cytokines, including interleukin (IL) -1beta, IL-4, IL-5, IL-6, IL-7, IL
      13, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage
      colony-stimulating factor. In the CD patients, the correlation was not
      significant except for IL-8. Our findings reflect different inflammatory states
      of the colon and rectum in both diseases. 

PMID- 25594640
TI  - A case report of idiopathic systemic capillary leak syndrome that occurred during
      the postoperative period of abdominoperineal resection for colorectal cancer.
AB  - A 57-year-old woman without any past medical history underwent abdominoperineal
      resection for rectal cancer in our department. On postoperative day 15, the
      patient complained of sudden abdominal pain, and high fever was noted in addition
      to the appearance of erythema around the stoma. The diagnosis of phlegmon was
      made, and antibiotic infusion was started. However, a few days later, the patient
      developed hypovolemic shock with hypoalbuminemia and hemoconcentration.
      Fasciotomy was performed to exclude the necrotizing fasciitis, though all
      cultures were negative. Upon exclusion of the differential diagnoses, idiopathic
      systemic capillary leak syndrome (ISCLS) was diagnosed. She was successfully
      treated with massive fluid infusion under ventilation and continuous
      hemodiafiltration. Here, we report the first case of ISCLS that occurred during
      the postoperative period of colorectal surgery. 

PMID- 25594639
TI  - Documented complications of staple hemorrhoidopexy: a systematic review.
AB  - A systematic review addressing reported complications of stapled hemorrhoidopexy
      was conducted. Articles were identified via searching OVID and MEDLINE between
      July 2011 and October 2013. Limitations were placed on the search criteria with
      articles published from 1998 to 2013 being included in this review. No language
      restrictions were placed on the search, however foreign language articles were
      not translated. Two reviewers independently screened the abstracts for relevance
      and their suitability for inclusion. Data extraction was conducted by both
      reviewers and entered and analyzed in Microsoft Excel. The search identified 784
      articles and 78 of these were suitable for inclusion in the review. A total of
      14,232 patients underwent a stapled hemorrhoidopexy in this review. Overall
      complication rates of stapled hemorrhoidopexy ranged from 3.3%-81% with 5
      mortalities documented. Early and late complications were defined individually
      with overall data suggesting that early complications ranged from 2.3%-58.9% and
      late complications ranged from 2.5%-80%. Complications unique to the procedure
      were identified and rates recorded. Both early and late complications unique to
      stapled hemorrhoidopexy were identified and assessed. 

PMID- 25594641
TI  - Improved health-related quality of life after surgical management of severe
      refractory constipation-dominant irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is the most common of the functional
      gastrointestinal disorders (FGIDs). Despite its prevalence and health-care costs,
      there are few effective therapies for patients with severe symptoms. Our
      objective was to determine whether surgical management would improve health
      related quality of life (HRQOL) in severe refractory constipation-dominant FGIDs.
      From 2003 to 2005, 6 patients underwent total colectomy with end ileostomy or
      primary anastomosis. They completed Short Form 36 (SF-36) and IBS-36
      questionnaires preoperatively and postoperatively. HRQOL was compared with age-
      and sex-matched Canadian norms using Welch's unpaired t test. Preoperative SF-36
      physical and mental health summary scores were significantly lower than Canadian
      norms (P < 0.0001), while postoperative scores were not significantly different
      than Canadian norms (P = 0.50 and P = 0.57, respectively). After surgical
      management, HRQOL in patients with severe constipation-dominant IBS improved from
      drastically below that of Canadian norms to a comparable level. This finding
      questions the convention of avoiding operations in IBS patients and demonstrates
      that surgical management may be suitable for the appropriately screened patient. 

PMID- 25594642
TI  - Impaired blood supply in the colonic anastomosis in mice compromises healing.
AB  - Colon anastomotic leakage has a multifactorial etiology and ischemia is
      considered one of the most important single factors. However, no existing animal
      models have established a direct link between ischemia and anastomotic leakage.
      The aim of this study was to establish a model of colon anastomotic leakage as a
      result of tissue ischemia. In colon anastomoses of 53 C57BL/6 mice, varying
      degrees of ischemia were induced. Supplying vessels were divided with bipolar
      coagulation in order to reduce anastomotic breaking strength and create clinical
      anastomotic leakage. Breaking strength of all the ischemic anastomoses were
      significantly lower compared with controls. Increasing ischemia resulted in
      higher rates of large bowel obstruction without creating anastomotic leakage.
      Healing was compromised as a result of impaired blood supply. However, clinical
      leakage was absent. Pure ischemia in otherwise healthy experimental animals may
      be too simple of an approach to create clinical leakage. 

PMID- 25594643
TI  - Emergency presenting colon cancer is an independent predictor of adverse disease
      free survival.
AB  - Twenty percent of colon cancers present as an emergency. However, the association
      between emergency presentation and disease-free survival (DFS) remains uncertain.
      Consecutive patients who underwent elective (CC) and emergent (eCC) resection for
      colon cancer were included in the analysis. Survival outcomes were compared
      between the 2 groups in univariate/multivariate analyses. A total of 439 patients
      underwent colonic resection for colon cancer during the interval 2000-2010; 97
      (22.1%) presented as an emergency. eCC tumors were more often located at the
      splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group
      displayed features of more advanced disease with a higher proportion of T4 (P =
      0.009), N2 tumors (P < 0.01) and lymphovascular invasion (P< 0.01). eCC was
      associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P <
      0.01 ) on univariate analysis. eCC remained an independent predictor of adverse
      locoregional recurrence (HR 1.86, 95% CI 1.50-3.30, P = 0.03) and DFS (HR 1.30,
      95% CI 0.88-1.92, P = 0.05) on multivariate analysis. eCC was not associated with
      adverse overall survival and systemic recurrence. eCC is an independent predictor
      of adverse locoregional recurrence and DFS. 

PMID- 25594644
TI  - The Preventive Effect of Dexmedetomidine Against Postoperative Intra-abdominal
      Adhesions in Rats.
AB  - This study aimed to determine the possible preventive effects of dexmedetomidine
      on postoperative intra-abdominal adhesions. Dexmedetomidine is a highly selective
      and potent alpha2 adrenergic agonist with sedative, analgesic, anxiolytic,
      sympatholytic, hemodynamic, and diuretic properties. In recent years,
      investigations have shown that dexmedetomidine possesses secondary antioxidant
      and also anti-inflammatory effects. Thirty Wistar albino male rats were
      randomized and divided into 3 groups of 10 animals each: group 1, sham-operated;
      group 2, cecal abrasion + peritoneal dissection; group 3, cecal abrasion +
      peritoneal dissection followed by daily intravenous injection of 10 MUg/kg
      dexmedetomidine for 10 days. The animals were killed on postoperative day 21.
      Blood and cecal samples were taken for biochemical and histopathologic
      evaluation. In this study, biochemical and pathologic parameters were
      significantly better in the cecal abrasion + peritoneal dissection +
      dexmedetomidine group when compared with the cecal abrasion + peritoneal
      dissection group. Tissue malondialdehyde, myeloperoxidase, total sulfhydryl, and
      catalase were found to be significantly different between the cecal
      abrasion/peritoneal dissection + dexmedetomidine and the cecal
      abrasion/peritoneal dissection groups. Plasma malondialdehyde and total
      sulfhydryl values were also statistically different between these groups (P <
      0.05). Statistical analyses of mean pathologic scores showed that the
      histopathologic damage in the cecal abrasion/peritoneal dissection +
      dexmedetomidine group was significantly less than the damage in the control group
      (P < 0.05 for all pathologic parameters). The results of this study show that
      dexmedetomidine had a significant preventive effect on postoperative intra
      abdominal adhesions. We concluded that these effects might be due to antioxidant
      and anti-inflammatory activities. 

PMID- 25594645
TI  - A novel bowel necrosis classification system and examination of patient outcomes
      in incarcerated groin hernia patients.
AB  - The objective of this study was to determine a classification system for BN in
      incarcerated groin hernia patients and to explore the possible relationship
      between BN staging and patient outcomes. Incarcerated groin hernia patients
      treated with emergency bowel resection from January 2008 to December 2013 were
      screened for inclusion in a prospective study. A novel three-stage classification
      system was proposed for BN (BN stages I-III) and correlations between adverse
      events (AEs) and mortality with BN stage were determined. A total of 108 patients
      were included, with 71, 26, and 11 patients in BN stages I, II, and III,
      respectively. AEs, which included wound and intra-abdominal infections and other
      systemic complications, increased with higher BN stage (all P < 0.05). Mortality
      increased with BN stage, with 2.8%, 7.7%, and 27.3% at BN stages I, II, and III,
      respectively (P < 0.05). The proposed BN staging system can objectively reflect
      the degree of bowel damage and its corresponding adverse outcomes. 

PMID- 25594646
TI  - A single case of single-port access laparoscopic appendectomy during the
      puerperium.
AB  - Laparoscopic appendectomy is now widely practiced for the treatment of acute
      appendicitis. As result of increased demand for minimally invasive surgery,
      single-incision access was introduced and is being performed in various abdominal
      surgeries. Conventional laparoscopic appendectomy (LA) is gradually being
      performed in pregnant women. A 33-year-old woman was referred to our department
      at 39 weeks and 1 day of gestation due to abdominal pain. She was aware of her
      gastroepiploic pain even after the delivery. Though it was past 2 days, she was
      not recovering from right lower abdominal pain, so she was transferred to the
      Department of Gynecology at our hospital on the same day. Although an antibiotic
      was administered, the right abdominal pain did not improve, and she was referred
      to our department from the Department of Gynecology. We performed single-port LA
      (SP-LA). The total operation time was 63 minutes, and the estimated blood loss
      was 0 mL. She was discharged with no complications on postoperative day 7. We
      report our initial experience with single-port LA (SP-LA) using the glove
      technique for treatment of acute appendicitis in a postpartum woman. SP-LA using
      the glove technique was performed successfully during the puerperium without
      prolongation of operation time. This approach is less invasive, offers a much
      better cosmetic result than with conventional methods, and can be performed
      safely and at low cost. 

PMID- 25594647
TI  - Value of extended warming in patients undergoing elective surgery.
AB  - Perioperative temperature management is imperative for positive surgical
      outcomes. This study assessed the clinical and wellbeing benefits of extending
      normothermia by using a portable warming gown. A total of 94 patients undergoing
      elective surgery were enrolled. They were randomized pre-operatively to either a
      portable warming gown or the standard warming procedure. The warming gown stayed
      with patients from pre-op to operating room to postrecovery room discharge. Core
      temperature was tracked throughout the study. Patients also provided responses to
      a satisfaction and comfort status survey. The change in average core temperature
      did not differ significantly between groups (P = 0.23). A nonsignificant 48%
      relative decrease in hypothermic events was observed for the extended warming
      group (P = 0.12). Patients receiving the warming gown were more likely to report
      always having their temperature controlled (P = 0.04) and significantly less
      likely to request additional blankets for comfort (P = 0.006). Clinical outcomes
      and satisfaction were improved for patients with extended warming. 

PMID- 25594648
TI  - Endometriosis in a spigelian hernia sac: an unexpected finding.
AB  - Describes the existence of endometrioma in a spigelian hernia sac. Spigelian
      Hernia is a rare ventral hernia, presenting difficulties in diagnosis and
      carrying a high incarceration and obstruction risk. Endometriomas occur due to
      implantation of endometrial cells into a surgical wound, most often after a
      cesarean delivery. A 37-year-old woman presented to our department with
      persistent abdominal pain, exacerbating during menses, and vomiting for 2 days.
      Physical examination revealed a mass-like lesion in the border between the left
      upper and left-lower quadrant. Ultrasound examination was inconclusive and a
      computed tomography scan of the abdomen revealed an abdominal wall mass. During
      surgery, a spigelian hernia was found 5 to 7 cm above a previous cesarean
      incision. Tissue like "chocolate cysts" was present at the hernia sac. Hernia was
      repaired while tissue was excised and sent for histological examination that
      confirmed the diagnosis. Spigelian hernia is a hernia presenting difficulties in
      diagnosis and treatment. Endometrioma in a spigelian hernia sac is a rare
      diagnosis, confirmed only histologically. Clinical suspicion can be posed only
      through symptoms and thorough investigation. 

PMID- 25594649
TI  - Role of chemotherapeutic agents in the management of cystic echinococcosis.
AB  - Hydatid disease is caused by infection with the metacestode stage of Echinococcus
      tapeworms of the family Taeniidae. The primary carriers are dogs and wolves, and
      humans are accidental hosts that do not contribute to the normal life cycle of
      this organism. The liver is the most commonly involved organ in the body by
      cystic echinococcosis (CE) secondary to infection with Echinococcus granulosus .
      Management options for CE should depend on the World Health Organization (WHO)
      diagnostic classification. Small (<5 cm) WHO stage CE1 and CE3a cysts may be
      primarily treated with benzimidazoles; the first-choice drug is albendazole. In
      some situations the combination of albendazole and praziquantel may be preferred.
      Chemotherapy with a benzimidazole or albendazole plus praziquantel is also used
      as adjunctive treatment to surgery and percutaneous treatment. Drug treatments
      have been the indispensable therapeutic modalities for cystic echinococcosis. 

PMID- 25594650
TI  - Laparoscopic excision versus open excision for the treatment of choledochal
      cysts: a systematic review and meta-analysis.
AB  - In 1723, Vater first described choledochal cyst and in 1977, Todani et al
      classified this disease. For many years, open excision (OP) as the standard
      procedure made a great impact in the treatment of choledochal cyst. Since 1995,
      when Farello et al first reported laparoscopic choledochal cyst excision,
      laparoscopic excision (LA) has been used worldwide. However, its safety remains a
      major concern. The aim of this meta-analysis was to compare OP with LA in
      treating choledochal cyst and then to determine whether LA is safe and valid. The
      design of this study involved systematic review and meta-analysis. Data sources
      were Medline, Ovid, Elsevier, Google Scholar, Embase, and Cochrane library. The
      study selection entailed comparative cohort studies. For data extraction, 2
      investigators independently assessed selected studies and extracted the following
      information: study characteristics, quality, outcomes data, etc. For the results,
      7 comparative cohort studies about the effectiveness of LA compared with OP were
      performed meta-analysis. The results showed that although the LA group had a
      longer operative time (MD = 56.57; 95% CI = 32.20-80.93; P < 0.00001), LA had a
      shorter duration of hospital stay (MD = -1.93; 95% CI = -2.51 to -1.36; P <
      0.00001), and recovery of bowel function (MD = -0.94; 95% CI = -1.33 to -0.55; P
      < 0.00001). Meta-analysis found no significant difference between most of the 2
      groups: bile leak (RR = 0.60; 95% CI = 0.29-1.24; P = 0.17), abdominal bleeding
      (RR = 0.33; 95% CI = 0.01-8.98; P = 0.51), pancreatitis (RR = 0.26, 95% CI = 0.06
      1.03; P = 0.06), total postoperative complications (RR = 1.04; 95% CI = 0.66
      1.62; P = 0.88). The LA group had significant lower rates in intraoperative blood
      transfusion (RR = 0.20; 95% CI = 0.11-0.38; P < 0.00001), and adhesive intestinal
      obstruction (RR = 0.17, 95% CI = 0.04-0.77; P = 0.02). In conclusion, compared
      with open excision, laparoscopic excision is a safe, valid, and feasible
      alternative to open excision. 

PMID- 25594651
TI  - Granulocyte colony-stimulating factor-producing cholangiocellular carcinoma.
AB  - A 61-year-old female was admitted to our hospital with epigastric pain and fever.
      The laboratory data showed severe inflammatory reactions. Computed tomography
      revealed an irregular tumor in the left hepatic lobe and swelling of lymph nodes.
      (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high
      uptake by the tumor, with diffuse uptake in the spine. Based on the elevated
      leukocyte count and FDG-PET findings, the patient was diagnosed with a
      granulocyte colony-stimulating factor (G-CSF)-producing tumor (G-CSF, 213 pg/mL).
      We performed left trisegmentectomy of the liver, bile duct resection, and lymph
      node dissection. Histologically, the tumor was a poorly differentiated
      adenocarcinoma with some lymph nodes metastasis. Immunohistochemical staining of
      the tumor cells was positive for G-CSF. Therefore, the tumor was diagnosed as G
      CSF-producing cholangiocellular carcinoma. The inflammatory reactions and serum G
      CSF level transiently improved immediately after surgery. However, 1 month later,
      the leukocyte count and serum G-CSF level increased again, and recurrence was
      observed in the remnant liver. The patient died 3 months after the operation. G
      CSF-producing cholangiocellular carcinoma is rare. This tumor progresses rapidly,
      and surgical treatment for advanced condition should be carefully selected. 

PMID- 25594652
TI  - Dedifferentiated liposarcoma involving the spleen and splenic hilum: a report of
      a case with a rare growth pattern.
AB  - We present a rare case of dedifferentiated liposarcoma confined to the spleen and
      splenic hilum. An 81-year-old man was referred to our hospital with a large
      asymptomatic splenic tumor. The patient underwent splenectomy, and the adipose
      tissue surrounding the splenic hilum was also resected. Microscopically, the
      tumor mainly consisted of high-grade spindle cells similar to those seen in
      undifferentiated pleomorphic liposarcoma. In the splenic hilum, scattered
      atypical cells were detected in the sclerosing component and adipose tissue.
      Immunohistochemically, both the spindle cells in the spleen and the atypical
      cells in the splenic hilum were positive for MDM2 and CDK4. The histopathologic
      diagnosis was dedifferentiated liposarcoma derived from an atypical lipomatous
      tumor/well-differentiated liposarcoma of the adipose tissue in the splenic hilum
      with extension into the spleen. Dedifferentiated liposarcoma in the spleen and
      splenic hilum should be considered as a differential diagnosis of splenic tumors.

PMID- 25594653
TI  - Intramedullary cervical tuberculoma: a case report with note on surgical
      management.
AB  - This study aims to report a relatively rare entity-intramedullary tuberculum of
      cervical spine-and describe its management and some key learning points.
      Intramedullary tuberculomas are rare entities. Intramedullary tuberculoma is most
      commonly found in the thoracic cord of a patient and is rarely seen in the
      cervical cord. We present an intramedullary cervical tuberculoma in a 21-year-old
      patient with finding of spinal cord compression. All 4 limbs were spastic, with
      grade 1 power on the right side and grade 3 power on the left side. Sensory
      deficit was found below the C6 level. Magnetic resonance imaging showed an
      intramedullary lesion at the C5 to C6 levels. Intramedullary tuberculoma was
      diagnosed based on clinical symptoms, physical examination, previous history, and
      magnetic resonance imaging. A C5 to C7 laminectomy was performed. Intramedullary
      tuberculoma was resected by microsurgery. One year after the surgery, strength
      returned to normal grade 5. Excellent clinical outcome was obtained with a
      combination of both medical and surgical treatments. Intramedullary cervical
      tuberculoma should be removed without delay to eliminate any mass effect on the
      neurons as soon as possible. 

PMID- 25594654
TI  - The impact of method on kidney graft and patient survival in kidney-pancreas
      transplantations for type I diabetes mellitus.
AB  - Patients who develop end-stage renal disease (ESRD) associated with Type I
      Diabetes Mellitus may receive kidney alone (KA) transplantation, simultaneous
      pancreas-kidney (SPK) transplantation, or a pancreas after kidney (PAK)
      transplantation. The goal of this study is to examine the long-term impact of
      pancreas transplantation on kidney graft and patient survival rates. A total of
      85 transplantation cases, consisting of 30 that received living donor KA, 21 that
      received SPK, and 34 that received PAK, from 2003-2010 at Akdeniz University
      Organ Transplantation Institute were retrospectively screened. There was a graft
      loss in 4 cases from the KA group, and in 1 case from each of the SPK and PAK
      groups. The five-year kidney graft survival rates were 86.7% in KA, 95.2% in SPK,
      and 97.1% in PAK. There was a single patient loss in both KA and SPK. The kidney
      survival percentages were higher in SPK and PAK groups compared to the KA group.
      Therefore, SPK should be the primary preference in these patients; however, for
      the cases that have a living donor, pancreas transplantation should be considered
      after kidney transplantation, or the patients can be followed-up on with close
      blood sugar control. 

PMID- 25594655
TI  - Equal 3-Year Outcomes for Kidney Transplantation Alone in HCV-Positive Patients
      With Cirrhosis.
AB  - Kidney transplantation alone in clinically compensated patients with cirrhosis is
      not well documented. Current guidelines list cirrhosis as a contraindication for
      kidney transplantation alone. This is an Institutional Review Board-approved
      retrospective study. We report our experience with a retrospective comparison
      between transplants in hepatitis C virus-positive (HCV(+)) patients without
      cirrhosis and HCV(+) patients with cirrhosis. All of the patients were followed
      for at least a full 3-year period. All of the deaths and graft losses were
      recorded and analyzed using Kaplan-Meier methodology. One- and three-year
      cumulative patient survival rates for noncirrhotic patients were 91% and 82%,
      respectively. For cirrhotic patients, one- and three-year cumulative patient
      survival rates were 100% and 83%, respectively (P = NS). One- and three-year
      cumulative graft survival rates censored for death were 94% and 81%, and 95% and
      82% for the noncirrhosis and cirrhosis groups, respectively (P = NS). Comparable
      patient and allograft survival rates were observed when standard kidney allograft
      recipients were analyzed separately. This study is the longest follow-up document
      in the literature showing that HCV(+) clinically ompensated patients with
      cirrhosis may undergo kidney transplantation alone as a safe and viable practice.

PMID- 25594657
TI  - Benign neck metastasis of a testicular germ cell tumor.
AB  - Germ cell tumors (GCTs) are relatively rare neoplasms considered to be curable
      malignancies since the introduction of cisplatin. The presence of neck metastasis
      has been reported, with fewer reports of metastatic mature teratoma. In this
      study, 3 cases of "benign neck" metastasis in patients with GCT between 1998 and
      2010 were reviewed retrospectively. In all 3 cases the presenting clinical sign
      was a left lower neck mass, leading to the diagnosis of the primary site in the
      testis. All had surgical salvage following chemotherapy, with benign lesions or
      mature teratoma in histopathology of the neck mass. Chemotherapy was followed by
      salvage lower-half neck dissection showing benign features in the neck specimen,
      even though malignancy was proven histologically in other areas. Only 1 patient
      had a postoperative chyle leak, which resolved spontaneously after several days.
      Neck dissection is recommended in those patients because malignancy cannot be
      excluded. 

PMID- 25594656
TI  - Anti-CD27 Antibody Potentiates Antitumor Effect of Dendritic Cell-Based Vaccine
      in Prostate Cancer-Bearing Mice.
AB  - In the current study, we investigated whether anti-CD27 monoclonal antibody can
      enhance the antitumor efficacy of a dendritic cell-based vaccine in prostate
      cancer-bearing mice. The overall therapeutic effect of a dendritic cell-based
      vaccine for prostate cancer remains moderate. A prostate cancer model was
      established by subcutaneous injection of RM-1 tumor cells into male C57BL/6 mice
      on day 0. After 4 days, tumor-bearing mice were treated with RM-1 tumor lysate
      pulsed dendritic cells (i.e., dendritic cell-based vaccine), anti-CD27 monoclonal
      antibody, or a combination of RM-1 tumor lysate-pulsed dendritic cells with anti
      CD27 monoclonal antibody. Mice were killed at 21 days after tumor cell
      implantation. Tumor size was measured for assessment of antitumor effect. Spleens
      were collected for analysis of antitumor immune responses. The antitumor immune
      responses were evaluated by measuring the proliferation and activity of T cells,
      which have the ability to kill tumor cells. The combination therapy with RM-1
      tumor lysate-pulsed dendritic cells and anti-CD27 antibody significantly enhanced
      T-cell proliferation and activity, and significantly reduced tumor growth,
      compared with monotherapy with RM-1 tumor lysate-pulsed dendritic cells or anti
      CD27 antibody. Our results suggest that combined treatment can strengthen
      antitumor efficacy by improving T-cell proliferation and activity. 

PMID- 25594658
TI  - Additional gastrectomy after endoscopic mucosal resection for early gastric
      cancer.
AB  - The aim of this study was to examine the clinicopathological characteristics of
      cases undergoing additional gastrectomy after endoscopic mucosal resection (EMR)
      for early gastric cancer (EGC) and the appropriate strategy for treating those
      after incomplete EMR. We studied 16 patients who underwent additional gastrectomy
      after EMR for EGC. The reasons for additional gastrectomy were positive
      horizontal margin (8 cases), indeterminate horizontal margin (2 cases), positive
      vertical margin (4 cases), submucosal invasion (7 cases), lymphatic invasion (4
      cases), venous invasion (1 case), and local recurrence (2 cases, including
      overlapped cases). Residual cancer was found in 6 of the 13 cases (46%), while no
      lymph node metastasis was found in any case; there were cases in which local
      resection was possible depending on tumor location and cases in which additional
      gastrectomy was performed due to suspected residual cancer but the specimens were
      free of cancer; follow-up without intervention appears to be feasible in some of
      these cases. When performing additional gastrectomy after EMR, the most
      appropriate method should be chosen so as not to worsen the quality of life of
      the patient while taking radical cure into consideration. 

PMID- 25594659
TI  - The use of serum uric acid concentration as an indicator of laparoscopic sleeve
      gastrectomy success.
AB  - Laparoscopic sleeve gastrectomy (LSG) effectively reduces weight by restricting
      gastric capacity and altering gut hormones levels. We designed a prospective
      study to investigate the correlation of serum uric acid (SUA) concentration and
      weight loss. SUA and body mass index (BMI) were measured preoperatively and on
      first postoperative month and year in patients who underwent LSG in our
      department of bariatric surgery. Data on 55 patients were analyzed. Preoperative
      SUA concentration had a significant positive correlation with percentage of total
      weight loss (TWL) on first postoperative month (P = 0.001) and year (P = 0.002).
      SUA concentration on first postoperative month had a positive correlation with
      percentage of TWL on first postoperative year (P = 0.004). SUA concentration
      could be used as a predictor of LSG's success and could help in early detection
      of patients with rapid loss of weight, in order to prevent complications. 

PMID- 25594660
TI  - Effectiveness of proton beam therapy on liver metastases of esophageal cancer:
      report of a case.
AB  - A 53-year-old man with multiple liver metastasis of esophageal cancer underwent
      four courses of chemotherapy. After four courses of chemotherapy, positron
      emission tomography showed progressive disease. Because it was difficult to
      control the cancer only by chemotherapy, we performed proton beam therapy (PBT)
      combined with chemotherapy. The irradiated parts were the primary tumor, liver
      metastases (S2/S4/S6), and mediastinal lymph nodes. The primary tumor including
      the mediastinal lymph nodes and the S2/S4/S6 metastases received proton beam
      irradiation at a total dose of 68.2 Gy in 31 fractions and 66.0 Gy in 30
      fractions, respectively, according to tumor location. This resulted in a complete
      response as shown by positron emission tomography. In our experience, PBT exerted
      a curative effect on liver metastases of esophageal cancer. It is thought that
      PBT may be effective in the treatment of esophageal cancer. This is the first
      report about PBT for liver metastases of esophageal cancer. 

PMID- 25594661
TI  - The management of varicose veins.
AB  - This study aimed to review the current management modalities for varicose veins.
      There are a variety of management modalities for varicose veins. The outcomes of
      the treatment of varicose veins are different. The papers on the management of
      varicose veins were reviewed and the postoperative complications and efficacy
      were compared. Foam sclerotherapy and radiofrequency ablation were associated
      with less pain and faster recovery than endovenous laser ablation and surgical
      stripping. Patients undergoing endovenous laser ablation and radiofrequency
      ablation are most likely to have a faster recovery time and earlier return to
      work in comparison with those undergoing conventional high ligation and
      stripping. A randomized controlled study in multiple centers is warranted to
      verify which approach is better than others for the treatment of varicose veins. 

PMID- 25594662
TI  - Surgical management of left upper quadrant sided rectus sheath hematoma occurred
      by coughing in a hemodialysis patient.
AB  - Rectus sheath hematoma (RSH) is a rarely-occurring disease that is usually
      associated with anticoagulation, trauma, or spontaneous events. Most spontaneous
      rectus sheath hematomas may be relieved with conservative management. However,
      some extreme situations need surgical approach. Respecting the fact that the
      inferior epigastric artery mainly supplies the rectus abdominis muscle,
      interrupting its proximal side would cease the bleeding. We present a stepped
      procedure of ligation of the inferior epigastric artery and evacuation of
      hematoma with good field of vision in case of rectus sheath hematoma in
      hemodialysis patient. 

PMID- 25594663
TI  - Primary hyperoxaluria complicated with liver cirrhosis: A case report.
AB  - Primary hyperoxaluria (PH) is a rare, autosomal recessive disorder characterized
      by overproduction of oxalate caused by a deficiency in a hepatic enzyme. The
      excess oxalate combines with calcium in the kidneys to form deposits of calcium
      oxalate, which can lead to nephrocalcinosis and renal failure. PH type 1 (PH1),
      the most common form of this disease, is caused by a deficiency of the liver
      specific enzyme alanine/glyoxylate aminotransferase (AGT). Liver transplantation
      is performed as a definitive therapy for PH to correct the enzyme defect.
      Usually, liver depositions are limited and liver function is normal without
      fibrosis. Here, we report an adult case of liver cirrhosis caused by PH1. A 28
      year-old woman was admitted to our hospital under suspicion of PH1 and the
      presence of nephrocalcinosis. The patient had suffered from kidney stone
      recurrences from 17 years of age, and was initiated on hemodialysis due to renal
      failure at the age of 27 years. The serum level of oxalic acid was high, whereas
      the AGT level in the liver tissue was decreased. Thus, the patient was
      definitively diagnosed with PH1. Although she had normal liver function, surface
      nodularity and splenomegaly were detected by computed tomography, suggesting
      liver cirrhosis. The native liver showed micronodular cirrhosis and portal
      fibrosis. Several arterioles were filled with rhomboid and polyhedral refractile
      oxalate crystals and various portal tracts showed these crystals. Our case
      suggests that long-term oxalosis can lead to liver cirrhosis; thus, PH should be
      considered one of the causes of liver cirrhosis. 

PMID- 25594664
TI  - Self-folding thermo-magnetically responsive soft microgrippers.
AB  - Hydrogels such as poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) can be
      photopatterned to create a wide range of actuatable and self-folding
      microstructures. Mechanical motion is derived from the large and reversible
      swelling response of this cross-linked hydrogel in varying thermal or pH
      environments. This action is facilitated by their network structure and capacity
      for large strain. However, due to the low modulus of such hydrogels, they have
      limited gripping ability of relevance to surgical excision or robotic tasks such
      as pick-and-place. Using experiments and modeling, we design, fabricate, and
      characterize photopatterned, self-folding functional microgrippers that combine a
      swellable, photo-cross-linked pNIPAM-AAc soft-hydrogel with a nonswellable and
      stiff segmented polymer (polypropylene fumarate, PPF). We also show that we can
      embed iron oxide (Fe2O3) nanoparticles into the porous hydrogel layer, allowing
      the microgrippers to be responsive and remotely guided using magnetic fields.
      Using finite element models, we investigate the influence of the thickness and
      the modulus of both the hydrogel and stiff polymer layers on the self-folding
      characteristics of the microgrippers. Finally, we illustrate operation and
      functionality of these polymeric microgrippers for soft robotic and surgical
      applications. 

PMID- 25594665
TI  - The isthmic nuclei providing parallel feedback connections to the avian tectum
      have different neurochemical identities: Expression of glutamatergic and
      cholinergic markers in the chick (Gallus gallus).
AB  - Retinal inputs to the optic tectum (TeO) triggered by moving stimuli elicit
      synchronized feedback signals from two isthmic nuclei: the isthmi parvocelullaris
      (Ipc) and isthmi semilunaris (SLu). Both of these nuclei send columnar axon
      terminals back to the same tectal position receiving the retinal input. The
      feedback signals from the Ipc seem to act as an attentional spotlight by
      selectively boosting the propagation of retinal inputs from the tectum to higher
      visual areas. Although Ipc and SLu nuclei are widely considered cholinergic
      because of their immunoreactivity for choline acetyltransferase (ChAT),
      contradictory findings, including the expression of the vesicular glutamate
      transporter 2 (VGluT2) mRNA in Ipc neurons, have raised doubts about the purely
      cholinergic nature of this nucleus. In this study, in chicks, we revise the
      neurochemical identity of the isthmic nuclei by using in situ hybridization
      assays for VGluT2 along with three cholinergic markers: the vesicular
      acetylcholine transporter (VAChT), the high-affinity choline transporter (CHT1)
      and ChAT. We found that neurons in the SLu showed strong mRNA expression of all
      three cholinergic markers, whereas the expression of VAChT mRNA in the Ipc was
      undetectable in our essays. Instead, Ipc neurons exhibited a strong expression of
      VGluT2 mRNA. Immunohistochemistry assays showed VGluT2 immunoreactivity in the
      TeO codistributing with anterogradely labeled Ipc axon-terminal boutons, further
      supporting a glutamatergic function for the Ipc nucleus. Therefore, our results
      strongly suggest that, in the chick, whereas the feedback from the SLu to the TeO
      is indeed cholinergic, the feedback from the Ipc has a marked glutamatergic
      component.

PMID- 25594666
TI  - Routine utilization of single-incision pediatric endosurgery (SIPES): a 5-year
      institutional experience.
AB  - BACKGROUND: Single-incision pediatric endosurgery (SIPES) allows operation
      through one access site, eliminating the multiple sites traditionally used. There
      are few large series evaluating the versatility of SIPES. The purpose of this
      study is to review a 5-year single-institution experience with routine SIPES use.
      PATIENTS AND METHODS: This is an Institutional Review Board-approved
      retrospective analysis of prospectively collected data. All SIPES cases from
      March 2009 to December 2013 were included. Our database contains demographics,
      procedure type, operative duration, estimated blood loss, instance of added ports
      or conversion to open, complications, and follow-up duration. RESULTS: Of 1322
      SIPES operations performed, most (82.1%) were appendectomies and
      cholecystectomies. Of 871 (66%) patients seen in follow-up, with a median
      duration of 26 days, 53 (6.1%) experienced postoperative complications. Forty-two
      cases (4.8%) were surgical-site infections, of which 4 required drainage. Less
      frequent complications that required operative intervention include recurrent
      inguinal hernia (n=4), umbilical hernia (n=3), intraabdominal abscess (n=1),
      bleeding (n=1), abdominal compartment syndrome (n=1), bowel obstruction (n=1),
      stitch granuloma (n=1), and persistent postoperative pain (n=1). CONCLUSIONS:
      Operative times and complication rates are comparable to those in prior reported
      multiport laparoscopic series, allowing safe integration of SIPES into the
      routine of a surgical practice for most common procedures.

PMID- 25594668
TI  - Patient Perception and Satisfaction with Implant Therapy in a Predoctoral Implant
      Education Program: A Preliminary Study.
AB  - PURPOSE: The purpose of this study was to assess the level of satisfaction and
      quality of life for patients receiving mandibular implant-supported overdenture
      (IOD) or single-tooth implant (STI) therapy in a predoctoral dental implant
      program. MATERIALS AND METHODS: Patients who received IOD and STI therapy and
      presented for recall visits at University of Illinois-Chicago College of
      Dentistry Predoctoral Implant Program were recruited. IOD treatment included
      placement of two endosseous implants in the mandibular canine region, followed by
      two abutments for resilient attachments. STI treatment included placement of
      endosseous implants, abutments, and cement-retained crowns. A modified Oral
      Health Impact Profile (OHIP)-14 questionnaire was given at least 6 months
      following insertion of implant-supported prostheses for both groups. Patient age,
      gender, distribution of STI, and OHIP-14 data were gathered and analyzed.
      Descriptive statistics were used to assess post-treatment data; Mann-Whitney U
      test was used to analyze the differences between groups older and younger than
      mean age and gender among the IOD and STI groups. RESULTS: Fifty-one consecutive
      patients in the IOD (60.7% male, 39.2% female, mean age 63.7) and 50 consecutive
      patients in the STI group (58.0% female, 42.0% male, mean age 50.8) were included
      in this recall study. In the STI group, 69 implants were placed for 50 patients;
      the most common region was the maxillary posterior quadrant (49.3%). Scores from
      modified OHIP-14 ranged from 0.14 to 0.78 for the IOD group and 0.02 to 0.18 for
      the STI group. Both IOD and STI data showed satisfaction with the treatment
      outcome. There was a significant difference found between men and women among the
      IOD group pertaining to questions regarding pronouncing words, sense of taste,
      meal interruption, and feeling embarrassed from OHIP-14, but not between the age
      groups. Also, no significant differences were noted for gender or age group
      within the STI patients and OHIP-14 scores. CONCLUSION: Dental implant therapy
      provided in a predoctoral setting had a significant impact on the quality of life
      and a high level of satisfaction for patients seeking implant treatment.

PMID- 25594669
TI  - Combinatorial screening of luminescent and structural properties in a Ce(3+)
      doped Ln-Al-Si-O-N (Ln = Y, La, Gd, Lu) system: the discovery of a novel
      Gd3Al(3+x)Si(3-x)O(12+x)N(2-x):Ce(3+) phosphor.
AB  - The discovery of novel phosphors for use in light emitting diodes (LED) has
      gained in significance because LED-based solid-state lighting applications now
      attract a great deal of attention for energy savings and environmental concerns.
      Recent research trends have centered on the discovery of novel phosphors, not on
      slight variations of well-known phosphors. In a real sense, novelty goes beyond
      simple variations or improvements in existing phosphors. A brilliant strategy for
      the discovery of novel phosphors is to introduce an appropriate activator to
      existing inorganic compounds. These compounds have structures that are well
      defined in crystallographic structure databases, but they have never been
      considered as a phosphor host. Another strategy is to discover new host compounds
      with structures that cannot be found in existing databases. We have
      simultaneously pursued both strategies by employing metaheuristics-assisted
      combinatorial material search techniques. In the present investigation, we
      screened a search space consisting of Ln-Al-Si-O-N (Ln = Y, La, Gd, Lu), and
      thereby we discovered a blue-light-emitting novel phosphor, Gd3Al(3+x)Si(3
      x)O(12+x)N(2-x):Ce(3+), with a monoclinic system in the C2 space group--a
      potential candidate for UV-LED applications.

PMID- 25594670
TI  - Risk factors and prognosis of isolated ischemic third, fourth, or sixth cranial
      nerve palsies in the Korean population.
AB  - BACKGROUND: To investigate the risk factors and prognosis for ischemic third,
      fourth, and sixth cranial nerve palsies in a Korean population. METHODS: A pair
      matched case-control study of 54 Korean patients who were diagnosed with ischemic
      third, fourth, or sixth cranial nerve palsies was performed to evaluate their
      risk factors. Using conditional logistic regression analysis, prevalence of
      potential risk factors in patients and controls, included diabetes mellitus,
      hypertension, hyperlipidemia, ischemic heart disease, left ventricular
      hypertrophy (LVH), and smoking were examined retrospectively. A cohort study by
      Kaplan-Meier method was performed to analyze the recovery period in relation to
      the number of risk factors or intracranial abnormalities detected by brain
      computed tomography or magnetic resonance imaging. RESULTS: The mean age of onset
      was 64.5 years. Of the 54 patients, 16 (29.6%) developed a third nerve palsy, 19
      (35.2%) a fourth nerve palsy, and 19 (35.2%) a sixth nerve palsy. The risk
      factors of diabetes mellitus, hypertension, and hyperlipidemia were significantly
      more prevalent than other risk factors of heart disease, LVH, and smoking. The
      mean number of risk factors was 2.3 +/- 0.6 in the third nerve palsy group, 1.7
      +/- 0.9 in the fourth nerve palsy group, and 1.6 +/- 1.0 in the sixth nerve palsy
      group. Patients with 2 or more risk factors showed a longer recovery period (9.0
      +/- 5.1 weeks) than did patients who had 1 risk factor (6.1 +/- 2.2 weeks).
      Patients with intracranial abnormalities on neuroimaging showed a longer recovery
      time (10.4 +/- 2.7 weeks) than did those without intracranial abnormalities (7.5
      +/- 4.8 weeks). CONCLUSIONS: Ischemic ocular motor cranial nerve palsy is closely
      related to diabetes mellitus, hypertension, and hyperlipidemia in Korean
      patients. Compared with the fourth or sixth nerve palsy groups, the third nerve
      palsy group showed a tendency to have multiple risk factors. Recovery takes
      longer when 2 or more risk factors were present or when abnormal findings were
      observed on neuroimaging.

PMID- 25594671
TI  - Bilateral sixth nerve palsies in anti-aquaporin 4 antibody syndrome.

PMID- 25594673
TI  - Abstracts of the ASTS 15th Annual State of the Art Winter Symposium, January 15
      18, 2014, Miami, FL.

PMID- 25594676
TI  - Proline-catalyzed sequential syn-Mannich and [4 + 1]-annulation cascade reactions
      to form densely functionalized pyrrolidines.
AB  - A highly efficient one-pot [4 + 1]-annulation process for the asymmetric
      synthesis of densely functionalized pyrrolidine derivatives is described. The in
      situ generated syn-Mannich adduct obtained via proline catalysis acts as a four
      atom component, and Corey's sulfur ylide or ethyl bromoacetate acts as a one-atom
      carbon source to construct pyrrolidine units in a highly enantio- and
      diastereoselective manner. 

PMID- 25594667
TI  - Chromatinization of the KSHV Genome During the KSHV Life Cycle.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus
      family and is the causative agent of various lymphoproliferative diseases in
      humans. KSHV, like other herpesviruses, establishes life-long latent infection
      with the expression of a limited number of viral genes. Expression of these genes
      is tightly regulated by both the viral and cellular factors. Recent advancements
      in identifying the expression profiles of viral transcripts, using tilling arrays
      and next generation sequencing have identified additional coding and non-coding
      transcripts in the KSHV genome. Determining the functions of these transcripts
      will provide a better understanding of the mechanisms utilized by KSHV in
      altering cellular pathways involved in promoting cell growth and tumorigenesis.
      Replication of the viral genome is critical in maintaining the existing copies of
      the viral episomes during both latent and lytic phases of the viral life cycle.
      The replication of the viral episome is facilitated by viral components
      responsible for recruiting chromatin modifying enzymes and replication factors
      for altering the chromatin complexity and replication initiation functions,
      respectively. Importantly, chromatin modification of the viral genome plays a
      crucial role in determining whether the viral genome will persist as latent
      episome or undergo lytic reactivation. Additionally, chromatinization of the
      incoming virion DNA, which lacks chromatin structure, in the target cells during
      primary infection, helps in establishing latent infection. Here, we discuss the
      recent advancements on our understating of KSHV genome chromatinization and the
      consequences of chromatin modifications on viral life cycle. 

PMID- 25594677
TI  - Overexpression of programmed death ligands in naturally occurring postweaning
      multisystemic wasting syndrome.
AB  - Postweaning multisystemic wasting syndrome (PMWS) is regarded as an
      immunosuppressive disease in pigs caused by porcine circovirus type 2 (PCV2).
      Immune inhibitory receptors, particularly programmed death 1/programmed death
      ligands (PD-1/PD-Ls) are presumably involved in the immunopathogenesis of PMWS.
      The aim of this investigation was to examine the relationship of immune
      inhibitory receptors and immunocompromised by PMWS. Nine 45-day-old conventional
      pigs were selected from a farm where pigs exhibited typical signs of PMWS
      (wasting and respiratory disorders) and tested positive for PCV2 infection by
      polymerase chain reaction (PCR). Six pigs were selected as controls due to their
      notably healthy state and absence of PCV2 infection. Heparinized blood samples
      were taken from each pig for pathogen detection and isolation of peripheral blood
      mononuclear cells (PBMCs), from which mRNA expression of immunomodulatory
      molecule (PD-1, PD-L1, PD-L2, PTEN, CTLA-4, LAG-3, and Foxp3) and cytokines (IL
      10, IL-2, and IFN-gamma) was determined. Proliferation of PBMCs was also assessed
      by flow cytometry utilizing cellular labeling dilutions for detection. The mRNA
      levels of PD-L1 (p<0.01), PD-L2 (p<0.05), and PTEN (p<0.01) were remarkably
      increased in the PBMCs of diseased pigs compared to healthy pigs, whereas no
      change was observed for PD-1, CTLA-4, LAG-3, and Foxp3 expression. Cytokine IL-10
      mRNA levels were significantly elevated (p<0.01), while IL-2 and IFN-gamma mRNA
      levels tended to be only slightly increased in the PBMCs of affected pigs
      compared to healthy controls. The proliferation of PBMCs was also decreased in
      diseased pigs. These data suggest that overexpression of PD-L1 and PD-L2 mRNA is
      one mechanism by which immunosupression of PMWS pigs occurs, supporting a new
      therapeutic strategy focused on PD-Ls for pigs suffering from PMWS. 

PMID- 25594678
TI  - "Vasovagal" response during ventricular fibrillation: incidence and implications.
AB  - BACKGROUND: The purpose of this study was to assess the relationship between
      changes in sinus node cycle length (SNCL) during ventricular fibrillation (VF)
      and the peripheral changes in blood pressure (BP) and sympathetic nerve activity
      (SNA) in human subjects. We hypothesized that patients with no SNCL shortening
      during VF have a vasovagal-like response with a greater decrease in BP and SNA
      when compared to patients with SNCL shortening. METHODS: SNCL, BP, and SNA
      recordings were attempted in 24 patients undergoing the implantation of a dual
      chamber implantable defibrillator. Changes were measured during the first 5
      seconds of VF and compared with the 5 seconds prior to VF induction. RESULTS:
      SNCL shortened during VF in nine patients (mean%?SNCL = -12 +/- 8%) and remained
      unchanged or lengthened in seven patients (mean%?SNCL = 7 +/- 7%). Eight patients
      had ventriculoatrial (VA) conduction prohibiting assessment of SNCL changes. In
      patients with SNCL shortening, the %?MBP (mean BP) was -47 +/- 6% compared to -58
      +/- 8% in patients with no SNCL shortening (P < 0.01). In patients with VA
      conduction, the %?MBP was -54 +/- 3%. SNA recordings were successfully obtained
      in four patients. When compared to baseline, SNA increased by 34 +/- 30% in two
      patients with SNCL shortening, decreased by 25% in one patient with SNCL
      lengthening, and by 90% in the fourth patient with VA conduction. CONCLUSIONS: We
      have shown that patients with no SNCL shortening have a significantly greater
      decrease in MBP during VF when compared to patients with SNCL shortening. The
      underlying mechanism appears to be reflex mediated with a vasovagal-like response
      in patients with no SNCL shortening.

PMID- 25594679
TI  - Ampakines enhance weak endogenous respiratory drive and alleviate apnea in
      perinatal rats.
AB  - RATIONALE: Apnea of prematurity, which is prevalent among infants born at less
      than 34 weeks gestation, is treated with caffeine, theophylline, or
      aminophylline. However, not all newborns respond adequately to, or tolerate,
      methylxanthine administration, and thus alternative pharmacological therapies are
      required. OBJECTIVES: Rodent models are used to test the hypothesis that the
      ampakine CX1739, a positive allosteric modulator of amino-3-hydroxy-5-methyl-4
      isoxazolepropionate receptors, strengthens perinatal respiratory drive and
      reduces apneas. We also provide a systematic study of the effects of caffeine for
      comparison. METHODS: Respiratory neural activity was recorded from brainstem
      spinal cord in vitro perinatal rat preparations, and [Formula: see text]e was
      recorded in newborn rat pups using whole-body plethysmography under normoxic and
      hypoxic conditions. MEASUREMENTS AND MAIN RESULTS: Using in vitro brainstem
      spinal cord preparations, we found that CX1739 (10-100 MUM) dose-dependently
      increases the frequency of respiratory activity generated by fetal and newborn
      rat preparations under normoxic and hypoxic conditions. Plethysmographic
      recordings in vivo from Postnatal Day 0 rats demonstrated that CX1739 (10 mg/kg)
      increases the frequency and regularity of ventilation, reduces apneas, and
      protects against hypoxia-induced respiratory depression. CONCLUSIONS: The net
      effect of ampakine enhancement of respiratory drive in perinatal rodents is a
      marked increase in ventilation and the regularity of respiratory patterns in
      perinatal rat preparations. Importantly, from the perspective of clinical
      applications, CX1739 readily crosses the blood-brain barrier, is metabolically
      stable, and has passed through phase I and II clinical trials in adults.

PMID- 25594680
TI  - Is the Great Barracuda (Sphyraena barracuda) a reef fish or a pelagic fish? The
      phylogeographic perspective.
AB  - Current taxonomy indicates a single global species of the Great Barracuda
      (Sphyraena barracuda) despite differences in color and behavior between Atlantic
      and Pacific forms. To investigate these differences and qualify the dispersal
      characteristics of this unique coastal- pelagic teleost (bony fish), we conducted
      a global phylogeographic survey of 246 specimens from thirteen sampling locations
      using a 629-base pair fragment of mtDNA cytochrome b. Data indicate high overall
      gene flow in the Indo-Pacific over large distances (>16,500 km) bridging several
      biogeographic barriers. The West Atlantic population contains an mtDNA lineage
      that is divergent from the Indo-Pacific (d = 1.9%), while the East Atlantic (N =
      23) has two mutations (d = 0.6%) apart from the Indo-Pacific. While we cannot
      rule out distinct evolutionary partitions among ocean basins based on behavior,
      coloration, and near-monophyly between Atlantic and Indo-Pacific subpopulations,
      more investigation is required before taxonomic status is revised. Overall, the
      pattern of high global dispersal and connectivity in S. barracuda more closely
      resembles those reported for large oceanic predators than reef-associated
      teleosts.

PMID- 25594681
TI  - Fast oxygen exchange and diffusion kinetics of grain boundaries in Sr-doped
      LaMnO3 thin films.
AB  - In this study, the contribution of grain boundaries to the oxygen reduction and
      diffusion kinetics of La0.8Sr0.2MnO3 (LSM) thin films is investigated.
      Polycrystalline LSM thin films with columnar grains of different grain sizes as
      well as epitaxial thin films were prepared by pulsed laser deposition. (18)O
      tracer exchange experiments were performed at temperatures from 570  degrees C to
      810  degrees C and subsequently analyzed by secondary ion mass spectrometry
      (SIMS). The isotope concentration depth profiles of polycrystalline films clearly
      indicate contributions from diffusion and surface exchange in grains as well as
      in grain boundaries. Measured depth profiles were analyzed by finite element
      modeling and revealed the diffusion coefficients D and oxygen exchange
      coefficients k of both the grain bulk and grain boundaries. Values obtained for
      grain boundaries (Dgb and kgb) are almost three orders of magnitude higher than
      those of the grains (Dg and kg). Hence, grain boundaries may not only facilitate
      fast oxygen diffusion but also fast oxygen exchange kinetics. Variation of the A
      site stoichiometry ((La0.8Sr0.2)0.95MnO3) did not lead to large changes of the
      kinetic parameters. Properties found for epitaxial layers without grain
      boundaries (Db and kb) are close to those of the grains in polycrystalline
      layers. 

PMID- 25594682
TI  - Development of a concise synthesis of ouabagenin and hydroxylated corticosteroid
      analogues.
AB  - The natural product ouabagenin is a complex cardiotonic steroid with a highly
      oxygenated skeleton. This full account describes the development of a concise
      synthesis of ouabagenin, including the evolution of synthetic strategy to access
      hydroxylation at the C19 position of a steroid skeleton. In addition, approaches
      to install the requisite butenolide moiety at the C17 position are discussed.
      Lastly, methodology developed in this synthesis has been applied in the
      generation of novel analogues of corticosteroid drugs bearing a hydroxyl group at
      the C19 position. 

PMID- 25594683
TI  - Structural evolution of colloidal crystal films in the process of melting
      revealed by Bragg peak analysis.
AB  - In situ X-ray diffraction studies of structural evolution of colloidal crystal
      films formed by polystyrene spherical particles upon incremental heating are
      reported. The Bragg peak parameters, such as peak position, integrated intensity,
      and radial and azimuthal widths were analyzed as a function of temperature. A
      quantitative study of colloidal crystal lattice distortions and mosaic spread as
      a function of temperature was carried out using Williamson-Hall plots based on
      mosaic block model. The temperature dependence of the diameter of polystyrene
      particles was obtained from the analysis of Bragg peaks, and the form factor
      contribution extracted from the diffraction patterns. Four stages of structural
      evolution in a colloidal crystal upon heating were identified. Based on this
      analysis, a model of the heating and melting process in the colloidal crystal
      film is suggested. 

PMID- 25594686
TI  - Three-dimensional observation of magnetic vortex cores in stacked ferromagnetic
      discs.
AB  - Electron holographic vector field electron tomography visualized three
      dimensional (3D) magnetic vortices in stacked ferromagnetic discs in a nanoscale
      pillar. A special holder with two sample rotation axes, both without missing
      wedges, was used to reduce artifacts in the reconstructed 3D magnetic vectors. A
      1 MV holography electron microscope was used to precisely measure the magnetic
      phase shifts. Comparison of the observed 3D magnetic field vector distributions
      in the magnetic vortex cores with the results of micromagnetic simulations based
      on the Landau-Lifshitz-Gilbert equation showed that the proposed technique is
      well suited for direct 3D visualization of the spin configurations in magnetic
      materials and spintronics devices. 

PMID- 25594685
TI  - Cocoa flavonoids protect hepatic cells against high-glucose-induced oxidative
      stress: relevance of MAPKs.
AB  - SCOPE: Oxidative stress plays a main role in the pathogenesis of type 2 diabetes
      mellitus. Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been
      suggested to exert beneficial effects in type 2 diabetes mellitus because of
      their protective effects against oxidative stress and insulin-like properties. In
      this study, the protective effect of EC and a cocoa phenolic extract (CPE)
      against oxidative stress induced by a high-glucose challenge, which causes
      insulin resistance, was investigated on hepatic HepG2 cells. METHODS AND RESULTS:
      Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs),
      nuclear factor E2 related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and
      glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and
      activated extracellular-regulated kinase and Nrf2. EC and CPE pre-treatment
      prevented high-glucose-induced antioxidant defences and p-MAPKs, and maintained
      Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in
      redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed
      in CPE-mediated protection. CONCLUSION: EC and CPE recovered redox status of
      insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE
      treated cells was protected against high-glucose-induced oxidative insult. CPE
      beneficial effects on redox balance and insulin resistance were mediated by
      targeting MAPKs.

PMID- 25594684
TI  - CD38 and airway hyper-responsiveness: studies on human airway smooth muscle cells
      and mouse models.
AB  - Asthma is an inflammatory disease in which altered calcium regulation,
      contractility, and airway smooth muscle (ASM) proliferation contribute to airway
      hyper-responsiveness and airway wall remodeling. The enzymatic activity of CD38,
      a cell-surface protein expressed in human ASM cells, generates calcium mobilizing
      second messenger molecules such as cyclic ADP-ribose. CD38 expression in human
      ASM cells is augmented by cytokines (e.g., TNF-alpha) that requires the
      activation of MAP kinases and the transcription factors, NF-kappaB and AP-1, and
      is post-transcriptionally regulated by miR-140-3p and miR-708 by binding to 3'
      Untranslated Region of CD38 as well as by modulating the activation of signaling
      mechanisms involved in its regulation. Mice deficient in Cd38 exhibit reduced
      airway responsiveness to inhaled methacholine relative to the response in wild
      type mice. Intranasal challenge of Cd38-deficient mice with TNF-alpha or IL-13,
      or the environmental fungus Alternaria alternata, causes significantly attenuated
      methacholine responsiveness compared with wild-type mice, with comparable airway
      inflammation. Reciprocal bone marrow transfer studies revealed partial
      restoration of airway hyper-responsiveness to inhaled methacholine in the Cd38
      deficient mice. These studies provide evidence for CD38 involvement in the
      development of airway hyper-responsiveness; a hallmark feature of asthma. Future
      studies aimed at drug discovery and delivery targeting CD38 expression and (or)
      activity are warranted. 

PMID- 25594687
TI  - Toxicity of a neonicotinoid insecticide, guadipyr, in earthworm (Eisenia fetida).
AB  - Neonicotinoid insecticides are new class of pesticides and it is very meaningful
      to evaluate the toxicity of guadipyr to earthworm (Eisenia fetida). In the
      present study, effects of guadipyr on reproduction, growth, catalase(CAT),
      superoxide dismutase (SOD), acetylcholinesterase (AChE) and DNA damage in
      earthworm were assessed using an artificial soil medium. Guadipyr showed low
      toxicity to earthworms and did not elicit an effect on earthworm reproduction or
      growth in artificial soils at concentrations <100mg/kg. However, after exposure
      to guadipyr, the activity of SOD and CAT in earthworm increased and then
      decreased to control level. AChE activity decreased at day 3 at 50 and 100mg/kg
      and then increased to control level. Our data indicate that guadipyr did not
      induce DNA damage in earthworms at concentration of <100mg/kg. 

PMID- 25594688
TI  - Improved biodegradation of textile dye effluent by coculture.
AB  - The present study demonstrates the de-colorization and degradation of textile
      effluent by coculture consisting of three bacterial species isolated from textile
      effluent contaminated environment with an aim to reduce the treatment time. The
      isolates were identified as Ochrobactrum sp., Pseudomonas aeruginosa and
      Providencia vermicola by 16S rRNA analysis. Their secondary structure was
      predicted and GC content of the sequence was found to be 54.39, 52.10, and
      52.53%. The co-culture showed a prominent increase in the degradation activity
      due to the action of oxidoreductase enzymatic mechanism of laccase, NADH-DCIP
      reductase and azoreductase activity. The biodegradability index of 0.75 was
      achieved with 95% chemical oxygen demand (COD) reduction in 16 h and 78 and 85%
      reduction in total organic carbon (TOC) and total solids was observed.
      Bioaccumulation of metals was identified by X-ray diffraction (XRD) analysis. The
      effective decolorization was confirmed from the results of UV-vis spectroscopy,
      high performance liquid chromatography and Fourier transformed infrared
      spectrometer analyzes. The possible degradation pathway was obtained from the
      analysis of liquid chromatography-mass spectroscopy analysis and the metabolites
      such as 2-amino naphthalene and N-phenyl-1.3,5 triazine were observed. The toxic
      nature of the effluent was analyzed using phyto-toxicity, cell-death assay and
      geno-toxicity tests.

PMID- 25594689
TI  - Noninvasive Detection of Functional Myocardial Ischemia: Multifunction Cardiogram
      Evaluation in Diagnosis of Functional Coronary Ischemia Study (MED-FIT).
AB  - BACKGROUND: Multifunction cardiogram (MCG) is a computer-enhanced, resting
      electrocardiogram analysis developed to detect hemodynamically relevant coronary
      artery disease (CAD). Based on data from previous studies suggesting excellent
      diagnostic accuracy in detecting CAD, MCG (approved by the Food and Drugs
      Administration) received a Current Procedure Terminology (CPT) code in 2010 in
      United States. However, there is no previous study validating MCG by using
      fractional flow reserve (FFR) as the reference standard. METHODS: Multifunction
      cardiogram Evaluation in Diagnosis of Functional coronary Ischemia sTudy (MED
      FIT) was designed as a single-center, prospective study enrolling 100 stable
      patients with suspected CAD scheduled for coronary angiography. The primary and
      secondary analyses evaluated the diagnostic performance of the MCG severity score
      to detect functional myocardial ischemia by FFR <=0.80, and angiographically
      significant coronary stenosis (percent diameter stenosis >=50%) by quantitative
      coronary angiography. RESULTS: The current analysis set consisted of 91 patients
      in whom MCG data with adequate quality was obtained. The prevalence of positive
      functional myocardial ischemia and angiographically significant stenosis in the
      current study was 42.7% and 41.8%, respectively. Area under the receiver
      operating characteristics curve (AUC) of the MCG severity score for functional
      myocardial ischemia and angiographically significant stenosis was low (AUC 0.51,
      95% confidence interval [CI] 0.38-0.63, and AUC 0.58, 95%CI 0.46-0.70,
      respectively). Sensitivity, and specificity of the MCG severity score for
      functional myocardial ischemia and angiographically significant stenosis was also
      low (32%/67%, and 37%/72%) using a cutoff value of 4.0. CONCLUSIONS: Diagnostic
      performance of the MCG severity score was poor for both functional myocardial
      ischemia, and angiographically significant stenosis.

PMID- 25594690
TI  - Preliminary data on carrion insects in urban (indoor and outdoor) and periurban
      environments in central Spain.
AB  - Although most cases involving entomological evidence occur in urban environments
      and under indoor conditions, there is a lack of studies determining the insect
      fauna of forensic importance in those environments. In the current paper we
      provide the first data on the composition of the forensically important insect
      species occurring in periurban and both indoor and outdoor urban environments in
      central Spain. Insects were collected fortnightly by means of carrion-baited
      traps, uninterruptedly during one year. Most species and individuals were
      collected in the periurban site, whereas the indoor urban site showed the lowest
      number of species and captures. Moreover, the composition of species differed
      among environments and seasons. A few species occurred under both indoor and
      outdoor conditions, including the blowfly Calliphora vicina and some
      Sarcophagidae species. These preliminary results suggest interesting differences
      in the insect composition between environments and conditions which may be of
      forensic importance, and represent a first step to further research into the
      application of insects to forensic investigations in urban environments of
      central Spain. 

PMID- 25594691
TI  - Instability of the hydrochloride salts of cathinone derivatives in air.
AB  - We observed the decomposition of the hydrochloride salt of alpha
      pyrrolidinoheptanophenone (alpha-PHPP-HCl), a newly distributed pyrrolidine-type
      cathinone derivative when 2.5ng of this substance was placed in glass test tubes
      and stored in a refrigerator for 3 days. To further investigate this phenomenon,
      we studied the (i) time course of the residual ratios of alpha-PHPP-HCl when a
      small amount (10MUg) of alpha-PHPP-HCl was stored in glass vials in air at room
      temperature; (ii) identification of the decomposition products of alpha-PHPP-HCl;
      (iii) effect of air on the decomposition process; (iv) effect of the added
      amounts of alpha-PHPP-HCl on its decomposition; and (v) comparison of the
      stability between various cathinone derivatives and their decomposition products.
      The decomposition of alpha-PHPP-HCl occurred in air and increased with time. Two
      possible decomposition products, alpha-(2"-oxopyrrolidino)heptanophenone and
      alpha-PHPP-N-oxide, were identified. These products were formed by oxygen in air
      because the yield significantly decreased by storing them in a vacuum desiccator.
      With the decrease in the amount of alpha-PHPP-HCl, the residual ratios decreased
      and amount of the decomposition products increased. This indicates that the
      decomposition of alpha-PHPP-HCl occurred on the upper surface of the samples. The
      hydrochloride salts of other cathinone derivatives were also unstable in air, and
      the residual ratios observed were different depending on the compounds. The
      pyrrolidine-type cathinone derivatives afforded two types of decomposition
      products, which were presumed to be 2"-oxo and N-oxide derivatives, similar to
      alpha-PHPP-HCl. In contrast, secondary amine-type cathinone derivatives showed
      different decomposition patterns, possibly including the dealkylated derivative.
      These findings may be very useful for the future toxicological analysis of
      cathinone derivatives. 

PMID- 25594692
TI  - Compassion fatigue among pediatric healthcare providers.
AB  - BACKGROUND: Compassion fatigue is a term used to describe the unique stressors
      affecting people in caregiving professions. PURPOSE: For nurses and other direct
      care providers, the impact of compassion fatigue may result in stress-related
      symptoms, job dissatisfaction, decreased productivity, decreased patient
      satisfaction scores, safety issues, and job turnover. Those who care for
      seriously ill children and their families are at increased risk for compassion
      fatigue. Constant exposure to children who are suffering, in combination with
      work place stressors and personal issues, may contribute to the development of
      compassion fatigue. METHODS: The Professional Quality of Life Scale Version 5 was
      used to determine the risk for compassion fatigue among 296 direct care providers
      at St. Louis Children's Hospital. RESULTS: Compassion satisfaction, burnout, and
      secondary traumatic stress scores did not differ by age, work category, level of
      education, or work experience. There were, however, significant differences in
      scores as a function of nursing unit. Nurses who work in the pediatric intensive
      care unit reported lower compassion satisfaction scores, and higher burnout and
      secondary traumatic stress scores. CLINICAL IMPLICATIONS: Results demonstrated
      the risk for compassion fatigue and provided data necessary to support
      development of a compassion fatigue program for direct care providers.

PMID- 25594693
TI  - Optimizing perioperative care for children and adolescents with challenging
      behaviors.
AB  - Pediatric perioperative nurses care for a wide variety of children and
      adolescents, some of whom have special developmental or behavioral needs.
      Providing care for this vulnerable population can be challenging because they may
      not express their level of pain or anxiety through behaviors commonly observed in
      typically developing children. This quality improvement project was conducted to
      enhance perioperative care delivered to children with challenging behaviors and
      to their families. A screening tool to individualize the plan of care was
      developed to identify specific behaviors, triggers, and communication patterns of
      these children prior to hospitalization. Interventions were identified to address
      these behaviors that could be used by nurses, child life specialists, and
      occupational therapists. Partnering with parents and other members of the
      interprofessional healthcare team has resulted in best practice care planning for
      these children, ensuring a much more successful perioperative experience for
      patients and families. Findings from parent surveys demonstrate that by using the
      tool, nurses and other team members are able to minimize stressors and implement
      interventions specific to the child. As a result, the adaptive care planning tool
      has expanded beyond the perioperative area and is now being used by direct care
      nurses, support staff, nurse practitioners, and physicians across the
      organization. 

PMID- 25594694
TI  - Beyond implementation: sustaining family-centered rounds.
AB  - Family-centered care encourages patients and families to participate in the
      planning and delivery of care based on personal preferences and individual needs.
      For pediatric patients and families, family-centered rounds (FCRs) represent a
      standard of care that involves patients and families partnering with the
      healthcare team to share information and make decisions about care. Our
      healthcare team strongly believes that FCRs are critical to providing excellence
      in care. Our initial attempt to implement and then sustain FCRs presented
      challenges that required changing the culture to one that consistently partners
      with patients and families and appreciates the role they play in the care of
      their children. Incorporation of observations and feedback from family advisors,
      a consistent process for rounding, and education for team members about
      expectations for participation were needed to revive and sustain FCRs. Through
      continued evaluation and collaboration, our unit worked to establish a standard
      approach to FCRs that benefits the patient and family as well as to the
      healthcare team. 

PMID- 25594697
TI  - gamma-Oryzanol protects pancreatic beta-cells against endoplasmic reticulum
      stress in male mice.
AB  - Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of beta
      cells under high-fat diet and hyperglycemia. Our recent study in mice showed that
      gamma-oryzanol, a unique component of brown rice, acts as a chemical chaperone in
      the hypothalamus and improves feeding behavior and diet-induced dysmetabolism.
      However, the entire mechanism whereby gamma-oryzanol improves glucose metabolism
      throughout the body still remains unclear. In this context, we tested whether
      gamma-oryzanol reduces ER stress and improves function and survival of pancreatic
      beta-cells using murine beta-cell line MIN6. In MIN6 cells with augmented ER
      stress by tunicamycin, gamma-oryzanol decreased exaggerated expression of ER
      stress-related genes and phosphorylation of eukaryotic initiation factor-2alpha,
      resulting in restoration of glucose-stimulated insulin secretion and prevention
      of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration
      of gamma-oryzanol improved glucose-stimulated insulin secretion on following
      reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the
      impact of gamma-oryzanol on low-dose streptozotocin-induced diabetic mice, where
      exaggerated ER stress and resultant apoptosis in beta-cells were observed. Also
      in this model, gamma-oryzanol attenuated mRNA level of genes involved in ER
      stress and apoptotic signaling in islets, leading to amelioration of glucose
      dysmetabolism. Taken together, our findings demonstrate that gamma-oryzanol
      directly ameliorates ER stress-induced beta-cell dysfunction and subsequent
      apoptosis, highlighting usefulness of gamma-oryzanol for the treatment of
      diabetes mellitus. 

PMID- 25594695
TI  - Excess iodide induces an acute inhibition of the sodium/iodide symporter in
      thyroid male rat cells by increasing reactive oxygen species.
AB  - Na+/I- symporter (NIS) mediates iodide (I-) uptake in the thyroid gland, the
      first and rate-limiting step in the biosynthesis of the thyroid hormones. The
      expression and function of NIS in thyroid cells is mainly regulated by TSH and by
      the intracellular concentration of I-. High doses of I- for 1 or 2 days inhibit
      the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect.
      The cellular mechanisms responsible for this physiological response are mediated
      in part by the inhibition of I- uptake through a reduction of NIS expression.
      Here we show that inhibition of I- uptake occurs as early as 2 hours or 5 hours
      after exposure to excess I- in FRTL-5 cells and the rat thyroid gland,
      respectively. Inhibition of I- uptake was not due to reduced NIS expression or
      altered localization in thyroid cells. We observed that incubation of FRTL-5
      cells with excess I- for 2 hours increased H2O2 generation. Furthermore, the
      inhibitory effect of excess I- on NIS-mediated I- transport could be
      recapitulated by H2O2 and reverted by reactive derived oxygen species scavengers.
      The data shown here support the notion that excess I- inhibits NIS at the cell
      surface at early times by means of a posttranslational mechanism that involves
      reactive derived oxygen species.

PMID- 25594696
TI  - Conditional expression of Pomc in the Lepr-positive subpopulation of POMC neurons
      is sufficient for normal energy homeostasis and metabolism.
AB  - Peptides derived from the proopiomelanocortin (POMC) precursor are critical for
      the normal regulation of many physiological parameters, and POMC deficiency
      results in severe obesity and metabolic dysfunction. Conversely, augmentation of
      central nervous system melanocortin function is a promising therapeutic avenue
      for obesity and diabetes but is confounded by detrimental cardiovascular effects
      including hypertension. Because the hypothalamic population of POMC-expressing
      neurons is neurochemically and neuroanatomically heterogeneous, there is interest
      in the possible dissociation of functionally distinct POMC neuron subpopulations.
      We used a Cre recombinase-dependent and hypothalamus-specific reactivatable
      PomcNEO allele to restrict Pomc expression to hypothalamic neurons expressing
      leptin receptor (Lepr) in mice. In contrast to mice with total hypothalamic Pomc
      deficiency, which are severely obese, mice with Lepr-restricted Pomc expression
      displayed fully normal body weight, food consumption, glucose homeostasis, and
      locomotor activity. Thus, Lepr+ POMC neurons, which constitute approximately two
      thirds of the total POMC neuron population, are sufficient for normal regulation
      of these parameters. This functional dissociation approach represents a promising
      avenue for isolating therapeutically relevant POMC neuron subpopulations.

PMID- 25594698
TI  - Thyrocyte-specific Dicer1 deficiency alters thyroid follicular organization and
      prevents goiter development.
AB  - MicroRNAs (miRNAs) are important regulators of posttranscriptional gene
      expression and involved in embryonic development, regulation of cell
      differentiation, and growth. Dicer1 is a key enzyme in the maturation process of
      functional miRNAs. However, miRNA-mediated regulation of normal thyroid function
      and growth is largely unknown. To understand the role of miRNAs in the thyroid,
      we generated constitutive and tamoxifen-inducible, thyrocyte-specific Dicer1
      knockout mice. The mice with perinatal Dicer1 deletion (cTgDcrKO) showed impaired
      follicular organization, increased fibrosis, and accumulation of adipocytes in
      the thyroid. Similar histological changes were observed in tamoxifen-induced
      adult Dicer1-deficient mice (iTgDcrKO). The thyroid phenotype in both knockout
      (KO) lines was associated with significantly down-regulated mRNA expression of
      thyroid transcription factor 1 (Ttf-1/Nkx2-1), thyroid peroxidase, and
      thyroglobulin (Tg) and up-regulated expression of genes involved in Tgf-beta
      signaling. Furthermore, in cTgDcrKO mice, which developed mild hypothyroidism,
      the protein expression of Nkx2-1, thyroglobulin, Paired box 8, and TSH receptor
      were clearly down-regulated compared with controls. Despite similar down
      regulation of Dicer1 in cTgDcrKO and iTgDcrKO compared with controls, Dicer1
      deletion in adult mice thyrocytes did not lead to acute hypothyroidism. No
      significant differences in thyroid weights between cTgDcrKO, iTgDcrKO, and
      controls were observed. However, a goitrogenic diet induced a 4-fold increase in
      thyroid weight in control animals, whereas it had no effect on iTgDcrKO thyroids.
      In summary, Dicer1 deficiency in thyrocytes is associated with intrathyroid
      fibrosis, adipogenesis, and enhanced expression of Tgf-beta signaling genes.
      Furthermore, our data indicate that Dicer1 is required for thyroid follicular
      organization, thyrocyte differentiation, and goiter development. 

PMID- 25594699
TI  - Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and
      after endotoxemia at the blood-brain barrier of male rodents.
AB  - There is increasing evidence that local thyroid hormone (TH) availability changes
      profoundly in inflammatory conditions due to altered expression of deiodinases
      that metabolize TH. It is largely unknown, however, how inflammation affects TH
      availability via the expression of TH transporters. In this study we examined the
      effect of bacterial lipopolysaccharide (LPS) administration on two TH
      transporters that are critically important for brain TH homeostasis, organic
      anion-transporting polypeptide 1c1 (OATP1c1), and monocarboxylate transporter 8
      (MCT8). MRNA levels were studied by in situ hybridization and qPCR as well as
      protein levels by immunofluorescence in both the rat and mouse forebrain. The
      mRNA of both transporters decreased robustly in the first 9 hours after LPS
      injection, specifically in brain blood vessels; OATP1c1 mRNA in astrocytes and
      MCT8 mRNA in neurons remained unchanged. At 24 and/or 48 hours after LPS
      administration, OATP1c1 and MCT8 mRNAs increased markedly above control levels in
      brain vessels. OATP1c1 protein decreased markedly in vessels by 24 hours whereas
      MCT8 protein levels did not decrease significantly. These changes were highly
      similar in mice and rats. The data demonstrate that OATP1c1 and MCT8 expression
      are regulated in a parallel manner during inflammation at the blood-brain barrier
      of rodents. Given the indispensable role of both transporters in allowing TH
      access to the brain, the results suggest reduced brain TH uptake during systemic
      inflammation. 

PMID- 25594700
TI  - Bisphenol A alters autonomic tone and extracellular matrix structure and induces
      sex-specific effects on cardiovascular function in male and female CD-1 mice.
AB  - The aim of this study was to determine whether bisphenol A (BPA) has adverse
      effects on cardiovascular functions in CD-1 mice and define sex-specific modes of
      BPA action in the heart. Dams and analyzed progeny were maintained on a defined
      diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) that resulted in BPA exposures
      from 4-5 to approximately 5000 MUg/kg . d or a diet containing 17alpha-ethinyl
      estradiol (EE; ~0.02, 0.2, and 0.15 MUg/kg . d) as an oral bioavailable estrogen
      control. Assessment of electrocardiogram parameters using noninvasive methods
      found that ventricular functions in both male and female mice were not altered by
      either BPA or EE. However, exposure-related changes in the rates of ventricular
      contraction, suggestive of a shift in sympathovagal balance of heart rate control
      toward increased parasympathetic activity, were detected in males. Decreased
      systolic blood pressure was observed in males exposed to BPA above 5 MUg/kg . d
      and in females from the highest BPA exposure group. Morphometric histological
      measures revealed sexually dimorphic changes in the composition of the cardiac
      collagen extracellular matrix, increases in fibrosis, and evidence of modest
      exposure-related remodeling. Experiments using the alpha-selective adrenergic
      agonist phenylephrine found that BPA enhanced reflex bradycardia in females, but
      not males, revealed that BPA and EE exposure sex specifically altered the
      sympathetic regulation of the baroreflex circuits. Increased sensitivity to the
      cardiotoxic effects of the beta-adrenergic agonist isoproterenol was observed in
      BPA- and EE-exposed females. This effect was not observed in males, in which BPA
      or EE exposures were protective of isoproterenol-induced ischemic damage and
      hypertrophy. The results of RNA sequence analysis identified significant sex
      specific changes in gene expression in response to BPA that were consistent with
      the observed exposure-related phenotypic changes in the collagenous and
      noncollagenous extracellular matrix, cardiac remodeling, altered autonomic
      responses, changes in ion channel and transporter functions, and altered
      glycolytic and lipid metabolism.

PMID- 25594702
TI  - Exploring the mechanism of salt-induced signal suppression in protein
      electrospray mass spectrometry using experiments and molecular dynamics
      simulations.
AB  - Protein analyses by electrospray ionization (ESI) mass spectrometry can suffer
      from interferences caused by nonvolatile salts. The mechanistic basis of this
      effect remains to be fully investigated. In the current work we explore the
      behavior of proteins under native and denaturing conditions in the presence of
      NaCl, CsCl, and tetrabutyl ammonium chloride (NBu4Cl). All three salts interfere
      with the formation of "clean" [M + zH](z+) protein ions by progressively
      deteriorating spectral S/N ratios. We propose that salt interferences can be
      dissected into two independent aspects, i.e., (i) peak splitting by adduct
      formation and (ii) protein ion suppression. NaCl degrades the spectral quality by
      forming heterogeneous [M + zH + n(Na - H) + m(Cl + H)](z+) ions, while the
      integrated protein ion intensity remains surprisingly robust. Conversely, NBu4Cl
      does not cause any adduction, while dramatically reducing the protein ion yield.
      These findings demonstrate that adduct formation and protein ion suppression are
      indeed unrelated effects that may occur independently of one another. Other
      salts, such as CsCl, can give rise to a combination of the two scenarios.
      Molecular dynamics simulations of water droplets charged with either Na(+) or
      NBu4(+) provide insights into the mechanism underlying the observed effects.
      Na(+) containing droplets evolve relatively close to the Rayleigh limit (z/z(R) ~
      0.74), whereas the z/z(R) values of NBu4(+) charged droplets are considerably
      lower (~0.59). This difference is due to the high surface affinity of NBu4(+),
      which facilitates charge ejection from the droplet. We propose that the low
      z/z(R) values encountered in the presence of NBu4(+) suppress the Rayleigh
      fission of parent droplets in the ESI plume, thereby reducing the yield of
      progeny droplets that represent the precursors of gaseous protein ions. In
      addition, the rate of solvent evaporation is reduced in the presence of NBu4(+).
      Both of these factors lower the protein signal intensity. NaCl does not interfere
      with droplet fission, such that protein ions continue to form with high yield
      albeit in heavily adducted form. Our findings expand on earlier proposals of
      charge competition as a key factor during the ESI process for salt-contaminated
      solutions.

PMID- 25594701
TI  - Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal
      ovarian function through promoting survival and overgrowth of ovarian follicles.
AB  - In this study, we explored the effects of oocytic phosphoinositide 3-kinase
      (PI3K) activation on folliculogensis by generating transgenic mice, in which the
      oocyte-specific Cre-recombinase induces the expression of constitutively active
      mutant PI3K during the formation of primordial follicles. The ovaries of neonatal
      transgenic (Cre+) mice showed significantly reduced apoptosis in follicles, which
      resulted in an excess number of follicles per ovary. Thus, the elevation of
      phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes the
      survival of follicles during neonatal development. Despite the increase in AKT
      phosphorylation, primordial follicles in neonatal Cre+ mice remained dormant
      demonstrating a nuclear accumulation of phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN). These primordial follicles containing a high level of
      nuclear PTEN persisted in postpubertal females, suggesting that PTEN is the
      dominant factor in the maintenance of female reproductive lifespan through the
      regulation of primordial follicle recruitment. Although the oocytic PI3K activity
      and PTEN levels were elevated, the activation of primordial follicles and the
      subsequent accumulation of antral follicles with developmentally competent
      oocytes progressed normally in prepubertal Cre+ mice. However, mature Cre+ female
      mice were anovulatory. Because postnatal day 50 Cre+ mice released cumulus-oocyte
      complexes with developmentally competent oocytes in response to super-ovulation
      treatment, the anovulatory phenotype was not due to follicular defects but rather
      endocrine abnormalities, which were likely caused by the excess number of
      overgrown follicles. Our current study has elucidated the critical role of
      oocytic PI3K activity in follicular function, as well as the presence of a PTEN
      mediated mechanism in the prevention of immature follicle activation. 

PMID- 25594703
TI  - Assessment and monitoring of liver function by 13C-aminopyrine breath test after
      selective transarterial chemoembolisation of hepatocellular carcinoma.
AB  - BACKGROUND: Liver function and tumor staging are essential parameters for
      selection of treatment modalities in patients with hepatocellular carcinoma
      (HCC). Transarterial chemoembolization (TACE) is associated with a risk of
      deterioration of liver function. In clinical routine hepatic function in patients
      with liver cirrhosis is assessed by the Child-Pugh-classification. Dynamic breath
      tests allow the assessment of the hepatic functional mass and have the potential
      to give more accurate information on hepatic function periinterventionally.
      PATIENTS AND METHODS: A prospective clinical study was performed in 13 patients
      receiving a total of 18 TACE sessions. (13)C-aminopyrine breath test was
      performed the day before TACE, 2 days and 30 days after TACE and correlated with
      standard laboratory work-up of the patients. RESULTS: Fourteen TACE sessions were
      performed in Child A liver cirrhosis, 4 in Child B cirrhosis. All patients
      presented with impaired aminopyrine metabolism at baseline. No significant
      changes in the (13)C aminopyrine breath test following TACE were observed. Two
      patients treated in Child A cirrhosis decompensated to Child B, one of them
      recovered. No further decompensation was observed in patients treated in Child B
      cirrhosis. DISCUSSION AND CONCLUSION: Liver function assessment with (13)C
      aminopyrine breath test and Child-Pugh-classification following TACE was
      discordant in a large proportion of patients. Whether a quantification of
      mitochondrial liver function in patients planned to undergo locoregional
      treatment of HCC in liver cirrhosis is helpful in the prediction of
      postprocedural liver decompensation needs to be addressed in larger prospective
      clinical trials.

PMID- 25594704
TI  - TIPS geometry influences patency.
AB  - OBJECTIVE: The purpose of this study was to evaluate potential causes of
      Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. MATERIAL AND
      METHODS: We retrospectively evaluated 26 patients who required TIPS revision
      (group I) and 24 patients who did not require any further intervention (group II)
      within the first two years following TIPS implantation. The distance of the
      distal end of the stent to the hepatocaval junction was measured. Furthermore,
      the angle between the stent and the portal vein (inflow) and the angle between
      the stent and the hepatic vein (outflow) were measured. Furthermore, the
      following data were evaluated: pre- and postinterventional portal pressure
      gradients, maximal postinterventional flow and blood values [C-reactive protein
      (CRP), bilirubin, glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic
      transaminase (GPT)]. RESULTS: Compared with control subjects, patients who
      required TIPS revision showed a significantly longer distance from the distal end
      of the stent to the hepatocaval junction (I: 17.3 +/- 10 mm, II: 6.7 +/- 5.7 mm,
      p < 0.001). There was a statistically significant correlation between the above
      named distance and the time to revision (Pearson's correlation coefficient, r =
      0.5, p = 0.01). In addition, patients with TIPS revision had a significantly
      larger angle of portalvenous inflow (alpha angle) than the control group (I:
      100.5 +/- 31.5 degrees , II: 64.5 +/- 31.6 degrees , p < 0.001). CONCLUSION: Our
      results show that the distance from the end of the stent to the hepatocaval
      junction and the angle of portalvenous inflow are technical factors that may
      influence the shunt's patency rate. Of these two, the distance to the hepatocaval
      junction can be influenced easily by the interventionalist.

PMID- 25594706
TI  - [Rituximab therapy for relapsing IgG4-autoimmune pancreatitis and cholangitis - a
      case report].
AB  - We report a patient with autoimmune pancreatitis and cholangitis. During a period
      of 3 years and despite therapy with steroids and immunmodulatory drugs such as
      azathioprine and mycophenolate mofetil he suffered from multiple relapse episodes
      including bile duct stenoses requiring endoscopic interventions. After initiation
      of therapy with the monoclonal CD20 antibody Rituximab, steroids could be stopped
      completely and the patient remains in remission. Rituximab should be considered
      in therapy of relapsing autoimmune pancreatitis and cholangitis. 

PMID- 25594705
TI  - MALDI imaging-based classification of hepatocellular carcinoma and non-malignant
      lesions in fibrotic liver tissue.
AB  - Histopathologic differentiation of nodular lesions in cirrhotic liver is
      difficult even for experienced hepatopathologists especially regarding diagnosis
      of hepatocellular carcinoma (HCC) in biopsies. For this reason, new tissue
      markers are needed to reinforce histopathologic decision-making. With advances in
      molecular techniques, proteomic analysis may help to confirm the diagnosis of
      HCC. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI
      IMS) is a powerful technology which allows to determine and to localize proteins
      directly in tissue sections. Using MALDI IMS proteomic patterns of cryosections
      with lesions of HCC (n = 15) and non-malignant fibrotic liver tissue (n = 11)
      were investigated to establish a classification model of HCC, which was validated
      in an independent set of tissue to distinguish HCC (n = 10) from regenerative
      nodules (n = 8). By correlating generated mass spectrometric images with the
      histology of the tissue sections we found that the expression of 4 proteins as
      indicated by m/z 6274, m/z 6647, m/z 6222 and m/z 6853 was significantly higher
      in HCC tissue than in non-tumorous liver tissue. The generated classification
      model based on the most significant 3 differentially expressed proteins allowed a
      reliable prediction of benign and malignant lesions in fibrotic liver tissue with
      a sensitivity and specificity of 90 % in the validation set. The identified MALDI
      IMS proteomic signature can be diagnostically helpful to allow simplifying the
      diagnostic process and minimize the risks of delays in establishing the objective
      final diagnosis and initiating treatment of patients with HCC.

PMID- 25594707
TI  - [Prescription of new HCV-drugs - what has to be considered judicially].
AB  - A unique specialty of the German public health insurance system is the option to
      hold a physician liable for the cost of medication considered not to be in line
      with the indication or to not to be used in a cost efficient way. Due to the high
      prices of direct acting antivirals (DAA) against the hepatitis C virus the
      potential financial losses are substantial. In addition, some of the public
      health insurance companies have already announced their intent to challenge the
      use of DAA. In this context the options as to how to minimise this risk are
      analysed within the given legal environment. 

PMID- 25594708
TI  - [Ultrasound after liver transplantation].
AB  - Graft specific complications after liver transplantation may be classified as
      vascular, biliar, and miscellaneous. This review provides an overview on
      sonography after liver transplantation. 

PMID- 25594709
TI  - [Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel
      disease].

PMID- 25594710
TI  - Risk perception, bias, and the role of the patient-doctor relationship in
      decision making about cerebral aneurysm surgery.

PMID- 25594711
TI  - Applying guidelines to individual patients: deep brain stimulation for early
      stage Parkinson disease.

PMID- 25594712
TI  - Duty-hour exceptions for neurosurgery residency programs.

PMID- 25594713
TI  - Evaluating simulation as a teaching tool in neurosurgery.

PMID- 25594714
TI  - Integrating ethics into science education and research: report of the
      presidential commission for the study of bioethical issues.

PMID- 25594715
TI  - Innovation in surgery and evidence development: can we have both at once?

PMID- 25594716
TI  - Models of neurosurgery international aid and their potential ethical pitfalls.

PMID- 25594717
TI  - A preparatory neuroethical approach to assessing developments in neurotechnology.

PMID- 25594718
TI  - Technological innovation and ethical response in neurosurgery.

PMID- 25594719
TI  - Disclosure of experience as a risk factor in informed consent for neurosurgery:
      the case of Johnson v. Kokemoor.

PMID- 25594720
TI  - The new era of neuromodulation.

PMID- 25594721
TI  - An antiferro-to-ferromagnetic transition in EuTiO(3-x)H(x) induced by hydride
      substitution.
AB  - We have prepared the oxyhydride perovskite EuTiO(3-x)H(x) (x <= 0.3) by a low
      temperature CaH2 reduction of pyrochlore Eu2Ti2O7 and perovskite EuTiO3. The
      reduced EuTiO(3-x)H(x) crystallizes in the ideal cubic perovskite (Pm3m), where
      O/H anions are randomly distributed. As a result of electron doping by the
      aliovalent anion exchange, the resistivity of EuTiO(3-x)H(x) shows metallic
      temperature dependence. Moreover, an antiferromagnetic-to-ferromagnetic
      transition is observed even when a small amount of hydride (x ~ 0.07) is
      introduced. The Curie temperature TC of 12 K is higher than those of any other
      EuTiO3-derived ferromagnets. The ferromagnetism can be explained by the Ruderman
      Kittel-Kasuya-Yosida (RKKY) interaction between the Eu(2+) spins mediated by the
      itinerant Ti 3d electrons. The present study shows that controlling the
      oxide/hydride ratio is a versatile method to tune magnetic and transport
      properties.

PMID- 25594722
TI  - Research ethics in the context of humanitarian emergencies.
AB  - Research is needed to make responses to disasters and humanitarian emergencies
      more evidence-based. Such research must also adhere to the generally accepted
      principles of research ethics. While research into health interventions used in
      disasters raises distinctive ethical concerns, seven ethical principles developed
      for clinical research are applied here to disaster research. Practical examples
      from disaster settings are used to demonstrate how these ethical principles can
      be applied. This reveals that research ethics needs to be seen as much more than
      a mechanism to obtain ethical approval for research. Research ethics involves
      ethical principles and governance frameworks, but must also consider the role of
      ethical virtues in research. Virtues are essential to ensure that researchers do
      what they believe is ethically right and resist what is unethical. Research
      ethics that truly protects participants and promotes respect needs to include
      training in ethical virtues to ensure disaster research is carried out to the
      highest ethical standards. This article is based on a presentation at the
      Evidence Aid Symposium on 20 September 2014, in Hyderabad, India. 

PMID- 25594723
TI  - Vitamin D production after UVB exposure - a comparison of exposed skin regions.
AB  - BACKGROUND: Cholecalciferol is an essential steroid produced in the skin by solar
      ultraviolet B radiation (UVB 290-315nm). Skin production of cholecalciferol
      depends on factors affecting UVB flux, age and exposed skin area. PURPOSE: Serum
      cholecalciferol and 25-hydroxyvitamin D3 [25(OH)D3] concentrations were measured
      after UVB irradiation of 3 different skin areas to compare the skin capacity to
      produce vitamin D in different anatomic sites in the same individuals. METHOD:
      Ten voluntary Caucasians (skin photo type II & III, aged 48+/-12years (+/-SD))
      were exposed to broadband UVB (280-320nm) between February and April. Hands and
      face, upper body and whole body were exposed to a suberythemic dose of UVB
      (median 101mJ/cm(2) (min 66, max 143)) (for 3 subsequent days 24h apart with a
      wash out period of about 3weeks (median 18days (min 11, max 25)) between the
      exposures of respective area. Serum concentrations of cholecalciferol and
      25(OH)D3, were measured immediately before the first and 24h after the last dose
      of radiation. RESULTS: There was a significantly higher increase in serum
      cholecalciferol after UVB exposure of the two larger skin areas compared to face
      and hands, but no difference in increase was found between upper body and whole
      body exposures. CONCLUSION: Exposure of a larger skin area was superior to small
      areas and gave greater increase in both serum cholecalciferol and serum 25(OH)D3
      concentrations. However, exposure of face and hands, i.e. only 5% of the body
      surface area, was capable of increasing serum concentrations of 25(OH)D3.

PMID- 25594725
TI  - A Call to Standardize Preanalytic Data Elements for Biospecimens, Part II.
AB  - CONTEXT: Biospecimens must have appropriate clinical annotation (data) to ensure
      optimal quality for both patient care and research. Additional clinical
      preanalytic variables are the focus of this continuing study. OBJECTIVE: To
      complete the identification of the essential preanalytic variables (data fields)
      that can, and in some instances should, be attached to every collected
      biospecimen by adding the additional specific variables for clinical chemistry
      and microbiology to our original 170 variables. DESIGN: The College of American
      Pathologists Diagnostic Intelligence and Health Information Technology Committee
      sponsored a second Biorepository Working Group to complete the list of
      preanalytic variables for annotating biospecimens. Members of the second
      Biorepository Working Group are experts in clinical pathology and microbiology.
      Additional preanalytic area-specific variables were identified and ranked along
      with definitions and potential negative impacts if the variable is not attached
      to the biospecimen. The draft manuscript was reviewed by additional national and
      international stakeholders. RESULTS: Four additional required preanalytic
      variables were identified specifically for clinical chemistry and microbiology
      biospecimens that can be used as a guide for site-specific implementation into
      patient care and research biorepository processes. CONCLUSIONS: In our collective
      experience, selecting which of the many preanalytic variables to attach to any
      specific set of biospecimens used for patient care and/or research is often
      difficult. The additional ranked list should be of practical benefit when
      selecting preanalytic variables for a given biospecimen collection.

PMID- 25594726
TI  - Potential hazards of brominated carbon sorbents for mercury emission control.
AB  - Mercury is a toxic air pollutant, emitted from the combustion of coal. Activated
      Carbon (AC) or other carbon sorbent (CS) injection into coal combustion flue
      gases can remove elemental mercury through an adsorption process. Recently, a
      brominated CS with biomass ash as the carbon source (Br-Ash) was developed as an
      alternative for costly AC-based sorbent for mercury capture. After mercury
      capture, these sorbents are disposed in landfill, and the stability of bromine
      and captured mercury is of paramount importance. The objective of this study is
      to determine the fate of mercury and bromine from Br-Ash and brominated AC after
      their service. Mercury and bromine leaching tests were conducted using the
      standard toxicity characteristic leaching procedure (TCLP). The mercury was found
      to be stable on both the Br-Ash and commercial brominated AC sorbents, while the
      bromine leached into the aqueous phase considerably. Mercury pulse injection
      tests on the sorbent material after leaching indicate that both sorbents retain
      significant mercury capture capability even after the majority of bromine was
      removed. Testing of the Br-Ash sorbent over a wider range of pH and liquid:solid
      ratios resulted in leaching of <5% of mercury adsorbed on the Br-Ash. XPS
      analysis indicated more organically bound Br and less metal-Br bonds after
      leaching. 

PMID- 25594724
TI  - Reduction of urease activity by interaction with the flap covering the active
      site.
AB  - With the increasing appreciation for the human microbiome coupled with the global
      rise of antibiotic resistant organisms, it is imperative that new methods be
      developed to specifically target pathogens. To that end, a novel computational
      approach was devised to identify compounds that reduce the activity of urease, a
      medically important enzyme of Helicobacter pylori, Proteus mirabilis, and many
      other microorganisms. Urease contains a flexible loop that covers its active
      site; Glide was used to identify small molecules predicted to lock this loop in
      an open conformation. These compounds were screened against the model urease from
      Klebsiella aerogenes, and the natural products epigallocatechin and quercetin
      were shown to inhibit at low and high micromolar concentrations, respectively.
      These molecules exhibit a strong time-dependent inactivation of urease that was
      not due to their oxygen sensitivity. Rather, these compounds appear to inactivate
      urease by reacting with a specific Cys residue located on the flexible loop.
      Substitution of this cysteine by alanine in the C319A variant increased the
      urease resistance to both epigallocatechin and quercetin, as predicted by the
      computational studies. Protein dynamics are integral to the function of many
      enzymes; thus, identification of compounds that lock an enzyme into a single
      conformation presents a useful approach to define potential inhibitors. 

PMID- 25594728
TI  - Halogenated boron-dipyrromethenes: synthesis, properties and applications.
AB  - Boron-dipyrromethene dyes (BODIPYs) containing halogens at pyrrole carbons are
      very useful synthons for the synthesis of a variety of BOIDPYs for a wide range
      of applications. Among the functional groups, halogens are the functional groups
      which can be regiospecifically introduced at any desired pyrrole carbon of the
      BODIPY framework by adopting appropriate synthetic strategies. The halogenated
      BODIPYs can undergo facile nucleophilic substitution reactions to prepare several
      interesting BODIPY based compounds. This review describes the synthesis,
      properties and potential applications of halogenated BODIPYs containing one to
      six halogens at the pyrrole carbons of the BODIPY core as well as properties and
      applications of some of the substituted BODIPYs derived from halogenated BODIPYs.

PMID- 25594727
TI  - A framework for establishing predictive relationships between specific bacterial
      16S rRNA sequence abundances and biotransformation rates.
AB  - The rates at which wastewater treatment plant (WWTP) microbial communities
      biotransform specific substrates can differ by orders of magnitude among WWTP
      communities. Differences in taxonomic compositions among WWTP communities may
      predict differences in the rates of some types of biotransformations. In this
      work, we present a novel framework for establishing predictive relationships
      between specific bacterial 16S rRNA sequence abundances and biotransformation
      rates. We selected ten WWTPs with substantial variation in their environmental
      and operational metrics and measured the in situ ammonia biotransformation rate
      constants in nine of them. We isolated total RNA from samples from each WWTP and
      analyzed 16S rRNA sequence reads. We then developed multivariate models between
      the measured abundances of specific bacterial 16S rRNA sequence reads and the
      ammonia biotransformation rate constants. We constructed model scenarios that
      systematically explored the effects of model regularization, model linearity and
      non-linearity, and aggregation of 16S rRNA sequences into operational taxonomic
      units (OTUs) as a function of sequence dissimilarity threshold (SDT). A large
      percentage (greater than 80%) of model scenarios resulted in well-performing and
      significant models at intermediate SDTs of 0.13-0.14 and 0.26. The 16S rRNA
      sequences consistently selected into the well-performing and significant models
      at those SDTs were classified as Nitrosomonas and Nitrospira groups. We then
      extend the framework by applying it to the biotransformation rate constants of
      ten micropollutants measured in batch reactors seeded with the ten WWTP
      communities. We identified phylogenetic groups that were robustly selected into
      all well-performing and significant models constructed with biotransformation
      rates of isoproturon, propachlor, ranitidine, and venlafaxine. These phylogenetic
      groups can be used as predictive biomarkers of WWTP microbial community activity
      towards these specific micropollutants. This work is an important step towards
      developing tools to predict biotransformation rates in WWTPs based on taxonomic
      composition. 

PMID- 25594730
TI  - Letter to the Editor: Thoracolumbar Injury Classification and Severity Score.

PMID- 25594729
TI  - Surgical outcomes of modified lumbar spinous process-splitting laminectomy for
      lumbar spinal stenosis.
AB  - The lumbar spinous process-splitting laminectomy (LSPSL) procedure was developed
      as an alternative to lumbar laminectomy. In the LSPSL procedure, the spinous
      process is evenly split longitudinally and then divided at its base from the
      posterior arch, leaving the bilateral paravertebral muscle attached to the
      lateral aspects. This procedure allows for better exposure of intraspinal nerve
      tissues, comparable to that achieved by conventional laminectomy while minimizing
      damage to posterior supporting structures. In this study, the authors make some
      modifications to the original LSPSL procedure (modified LSPSL), in which
      laminoplasty is performed instead of laminectomy. The purpose of this study was
      to compare postoperative outcomes in modified LSPSL with those in conventional
      laminectomy (CL) and to evaluate bone unions between the split spinous process
      and residual laminae following modified LSPSL. Forty-seven patients with lumbar
      spinal stenosis were enrolled in this study. Twenty-six patients underwent
      modified LSPSL and 21 patients underwent CL. Intraoperative blood loss and
      surgical duration were evaluated. The Japanese Orthopaedic Association (JOA)
      scale scores were used to assess parameters before surgery and 12 months after
      surgery. The recovery rates were also evaluated. Postoperative paravertebral
      muscle atrophy was assessed using MRI. Bone union rates between the split spinous
      process and residual laminae were also examined. The mean surgical time and
      intraoperative blood loss were 25.7 minutes and 42.4 ml per 1 level in modified
      LSPSL, respectively, and 22.7 minutes and 29.5 ml in CL, respectively. The
      recovery rate of the JOA score was 64.2% in modified LSPSL and 68.7% in CL. The
      degree of paravertebral muscle atrophy was 7.8% in modified LSPSL and 22.2% in CL
      at 12 months after surgery (p < 0.05). The fusion rates of the spinous process
      with the arcus vertebrae at 6 and 12 months in modified LSPSL were 56.3% and
      81.3%, respectively. The modified LSPSL procedure was less invasive to the
      paravertebral muscles and could be a laminoplasty; therefore, the modified LSPSL
      procedure presents an effective alternative to lumbar laminectomy. 

PMID- 25594731
TI  - Should we use cortical bone screws for cortical bone trajectory?
AB  - OBJECT: In 2009, Santoni et al. reported cortical bone trajectory (CBT) as a
      method of inserting pedicle screws to obtain more solid fixation, and proposed
      the use of cortical trajectory screws with a more closely placed thread (cortical
      screws) for CBT. Since the entry trajectory in CBT differs from that in the
      traditional trajectory, it is unclear whether the increased strength derives from
      the specific trajectory or the shape of the screw thread in contact with the
      cortical bone. Whether the use of cortical screws is always required with CBT
      thus remains unclear. The authors therefore investigated the relationship between
      screw entry trajectory and screw thread characteristics and pullout strength in
      animal experiments. METHODS: Lumbar vertebrae (L1-L4) from 4-month-old female
      pigs were randomly assigned to one of 4 groups, with cancellous screws or
      cortical screws inserted via the traditional trajectory or CBT. For pullout
      strength testing, the screw was pulled out vertically against the direction of
      insertion. Rod pullout testing (toggle testing) was also performed, and the peak
      breaking strength was measured. RESULTS: The maximum pullout strength was
      significantly greater for CBT using cortical screws than for the traditional
      trajectory using cancellous screws. Pullout strength tended to be higher when
      cortical screws were used in both CBT and the traditional trajectory, although
      the difference was not significant. Toggle testing showed no significant
      differences among the 4 groups. CONCLUSIONS: The specific unconventional
      trajectory seemed to have a major impact on the increased strength obtained with
      CBT.

PMID- 25594732
TI  - Malignant Melanoma Arising in Patients with a Large Congenital Melanocytic
      Naevus: Retrospective Study of 10 Cases with Cytogenetic Analysis.
AB  - Large congenital melanocytic naevi (LCMN) represent the main risk factor for
      development of melanoma in childhood. This retrospective study of 10 cases of
      melanoma in patients with LCMN used fluorescence in situ hybridization (FISH) and
      comparative genomic hybridization (CGH) (6 cases) to elucidate the clinical,
      histological, and cytogenetic characteristics of this rare disorder. Six
      melanomas were found within the LCMN, the others in lymph nodes, subcutis and
      brain. The LCMN was located on the trunk in 8 cases, with satellite naevi in 6
      cases. Two distinct groups emerged: 5 melanomas that developed before the age of
      10 years and the other after 20 years. The mortality rate was 60% and clearly
      correlated with clinical stage at diagnosis. Histological diagnosis was difficult
      in only 2 patients in whom neither immunohistochemistry nor FISH were helpful.
      Otherwise, CGH showed a high number of chromosomal aberrations leading to a
      formal diagnosis.

PMID- 25594734
TI  - Spontaneous live recurrent ectopic pregnancy after ipsilateral partial
      salpingectomy leading to tubal rupture.
AB  - INTRODUCTION: Ectopic pregnancy accounts for 1-2% of all pregnancies in the
      United States. The most common site of implantation for an ectopic pregnancy is
      the fallopian tube. We present the first case describing a recurrent ectopic
      pregnancy with a fetal heartbeat after ipsilateral salpingectomy that led to
      tubal rupture. PRESENTATION OF CASE: The patient presented with abdominal pain
      approximately six weeks after her last menstrual period. Seven years prior to
      presentation, a laparoscopic partial right salpingectomy had been performed for a
      tubal ectopic pregnancy. Physical exam was significant for diffuse abdominal
      tenderness and guarding. Ultrasonography revealed a right tubal pregnancy with a
      fetal pole and a fetal heart rate that was calculated to be 108 beats per minute.
      Free fluid was also noted. 1.5l of hemoperitoneum was subsequently evacuated and
      the right fallopian tube remnant with the ectopic pregnancy was removed.
      Pathology of the tubal remnant showed immature chorionic villi and fetal parts.
      DISCUSSION: The mechanism by which a recurrent ectopic pregnancy after
      ipsilateral salpingectomy occurs is unclear, but is theorized to be secondary to
      contralateral fertilization and/or tubal recanalization that may occur due to
      inadequate diathermy. CONCLUSION: Physicians should be aware that ectopic
      pregnancies may not only occur repeatedly but may also present a typically. We
      recommend when performing a salpingectomy that efforts be undertaken to minimize
      the length of the tubal remnant and to assure adequate coagulation of tissue so
      as to reduce the risk of recurrence.

PMID- 25594733
TI  - Important poisonous plants in tibetan ethnomedicine.
AB  - Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and
      unique cultural background. Many poisonous plants have been widely used to treat
      disorders in the Tibetan medicinal system. In the present review article, some
      representative poisonous plant species are introduced in terms of their
      significance in traditional Tibetan medicinal practices. They are Aconitum
      pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for
      which the toxic chemical constituents, bioactivities and pharmacological
      functions are reviewed herein. The most important toxins include aconitine,
      strychnine, scopolamine, and anisodamine. These toxic plants are still currently
      in use for pain-reduction and other purposes by Tibetan healers after processing.

PMID- 25594735
TI  - A rare case of gingival metastases from papillary thyroid carcinoma.
AB  - Metastatic oral malignancy accounts for 1% of all oral cancers. Oral soft tissue
      involvement is rare and accounts for less than 0.1% of all oral tumours with the
      attached gingiva being the commonest site affected. We present the first reported
      case of a papillary thyroid carcinoma (PTC) with sarcomatoid transformation
      giving rise to gingival metastasis. A 71 year old man with a history of PTC
      presented with an asymptomatic gingival swelling adjacent to his lower right
      lateral incisor. Subsequent biopsy of the lesion confirmed PTC metastasis with
      aggressive sarcomatoid features. We present a clinical photograph of the gingival
      swelling and the pathology images demonstrating both the papillary and
      sarcomatoid features of the gingival biopsy. The prognosis of PTC is usually
      excellent but some histological variants of PTC behave more aggressively. The
      histology in our case demonstrated solid areas and sarcomatoid transformation and
      behaved far more aggressively than typical PTC. Sarcomatoid transformation in PTC
      has not been previously described and indicates a poor prognosis and the need for
      planning urgent palliation. These lesions can present a diagnostic challenge to
      both pathologists and clinicians in identifying the lesion as metastatic and
      locating the primary cancer. This case demonstrates the need for vigilance
      amongst health professionals when presented with an oral soft tissue mass in
      patients with a known primary malignancy. This may be the first evidence of
      disseminated disease and emphasises a low threshold to biopsy oral soft tissue
      lesions in patients with a history of malignant disease. 

PMID- 25594736
TI  - Transitional mesh repair for large incisional hernia in the elderly.
AB  - INTRODUCTION: Large incisional hernias are difficult to repair, especially in
      elderly patients with thin abdominal walls. Although most such incisional hernias
      are simply observed, they do not spontaneously resolve. Previously reported
      procedures are inadequate for repair of all incisional hernias. We herein propose
      an innovative technique for repair of ventral incisional hernias. PRESENTATION OF
      CASE: A 88-year-old woman had a large incisional hernia with bilateral inguinal
      hernias. Incisional hernioplasty was successfully performed for extraperitoneal
      reinforcement by combining underlay and onlay methods using one prosthesis with
      transitional sutures. Bilateral inguinal hernioplasty was performed
      simultaneously. Twelve months postoperatively, the patient is well, without
      hernia recurrence. DISCUSSION: Elderly patients often have thin, attenuated
      abdominal walls, and large incisional hernia reinforcement may require a
      prosthesis. In such cases, a retrorectal prosthesis position is recommended.
      However, the prosthesis cannot be placed on the cranial side in the presence of a
      destroyed or adhered abdominal wall is present. In this case, one prosthesis was
      placed using an underlay method on the caudal side and using an onlay method on
      the cranial side. The abdominal layers were shifted and each transition point was
      covered by the other layers to secure the overlapping margins between the
      abdominal wall and prosthesis. CONCLUSION: This transitional mesh repair was
      successfully performed for a large incisional hernia in an elderly patient. The
      procedure is a useful strategy for incisional hernia repair in patients with
      thin, destroyed abdominal walls. However, further studies are required for a more
      thorough evaluation of this technique.

PMID- 25594738
TI  - The effects of antidepressant medications on mothers and babies.
AB  - Depression during pregnancy may be undertreated for a variety of reasons, one of
      which is concern regarding the safety of antidepressant medication. Dr.
      Grigoriadis leads a program of research to develop a reference guide to
      facilitate perinatal treatment discussions. The clinical group has published
      systematic reviews and meta-analyses on various potential outcomes following
      antidepressant exposure (i.e., congenital anomalies, spontaneous abortion,
      delivery outcomes, immediate neonatal outcomes and persistent pulmonary
      hypertension) in addition to outcomes associated with maternal depression. Some
      of the results of this program of research are presented together with a case
      example to start your thinking on the issues.

PMID- 25594737
TI  - Investigation of enzymatic C-P bond formation using multiple quantum HCP nuclear
      magnetic resonance spectroscopy.
AB  - The biochemical mechanism for the formation of the C-P-C bond sequence found in l
      phosphinothricin, a natural product with antibiotic and herbicidal activity,
      remains unclear. To obtain further insight into the catalytic mechanism of PhpK,
      the P-methyltransferase responsible for the formation of the second C-P bond in l
      phosphinothricin, we utilized a combination of stable isotopes and two
      dimensional nuclear magnetic resonance spectroscopy. Exploiting the newly emerged
      Bruker QCI probe (Bruker Corp.), we specifically designed and ran a (13) C-(31) P
      multiple quantum (1) H-(13) C-(31) P (HCP) experiment in (1) H-(31) P two
      dimensional mode directly on a PhpK-catalyzed reaction mixture using (13) CH3 
      labeled methylcobalamin as the methyl group donor. This method is particularly
      advantageous because minimal sample purification is needed to maximize product
      visualization. The observed 3:1:1:3 multiplet specifically and unequivocally
      illustrates direct bond formation between (13) CH3 and (31) P. Related nuclear
      magnetic resonance experiments based upon these principles may be designed for
      the study of enzymatic and/or synthetic chemical reaction mechanisms.

PMID- 25594739
TI  - Novel sesquiterpenes from Schisandra grandiflora: isolation, cytotoxic activity
      and synthesis of their triazole derivatives using "click" reaction.
AB  - Phytochemical investigation of hexane extract from the fruits of Schisandra
      grandiflora afforded three novel sesquiterpenes (1-3) along with the three known
      compounds (4-6). The structures of these isolates were determined by extensive
      analysis of spectroscopic data (1D, 2D NMR). Further, a series of triazole
      analogues of 3 and 4 were prepared using "Click" reaction protocol. The reaction
      scheme involving one-carbon homologation of 3 and 4 using the Bestmann-Ohira
      reagent followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction of
      various azides leading to the formation of triazole analogues (20a-20k &21a-21c)
      which is being reported for the first time. All the triazole products were
      characterized using spectral data analysis. The anti-proliferative activity of
      the isolates and the synthetic analogues were studied against Hela (Cervical
      cancer), A549 (Lung cancer), DU-145 (Prostate cancer), MCF-7 (Breast cancer) and
      B-16 (Mouse melanoma) cancer cell lines. 

PMID- 25594740
TI  - Identification of novel aminothiazole and aminothiadiazole conjugated
      cyanopyridines as selective CHK1 inhibitors.
AB  - Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential
      anti-tumor agents. Novel series of cyanopyridyl-aminothiadiazoles (synthesized
      from reaction of 1-(3-cyano-4,6-diphenylpyridin-2-yl)-3-phenylthiourea (14) with
      hydrazonoyl halides) and cyanopyridyl-aminothiazolyl-thiadiazoles (synthesized
      from treatment of 14 with ethyl chloroacetate followed by reaction of the
      obtained cyanopyridyl-aminothiazole with hydrazonoyl halides) were synthesized
      and evaluated for their CHK1 inhibitory potential using a cell-based assay
      cascade. The tested compounds exhibited a potent and selective CHK1 inhibitory
      activity at nanomolar levels that reflected their ability to abrogate cell cycle
      arrest and potentiate the cytotoxic effect of the genotoxic drug gemcitabine in
      colon cancer cells. Molecular modeling simulation revealed that, the most active
      compound 28a docked well into the enzyme active site and their complex is
      stabilized by a key H-bonding with the backbone amide of Cys-87 as well as
      multiple favorable hydrophobic interactions with different hydrophobic binding
      regions of the enzyme. 

PMID- 25594742
TI  - Charcoal-inferred Holocene fire and vegetation history linked to drought periods
      in the Democratic Republic of Congo.
AB  - The impact of Holocene drought events on the presumably stable Central African
      rainforest remains largely unexplored, in particular the significance of fire.
      High-quality sedimentary archives are scarce, and palynological records mostly
      integrate over large regional scales subject to different fire regimes. Here, we
      demonstrate a direct temporal link between Holocene droughts, palaeofire and
      vegetation change within present-day Central African rainforest, using records of
      identified charcoal fragments extracted from soil in the southern Mayumbe forest
      (Democratic Republic of Congo). We find three distinct periods of local
      palaeofire occurrence: 7.8-6.8 ka BP, 2.3-1.5 ka BP, 0.8 ka BP - present. These
      periods are linked to well-known Holocene drought anomalies: the 8.2 ka BP event,
      the 3rd millennium BP rainforest crisis and the Mediaeval Climate Anomaly. During
      and after these Holocene droughts, the Central African rainforest landscape was
      characterized by a fragmented pattern with fire-prone open patches. Some fires
      occurred during the drought anomalies although most fires seem to lag behind
      them, which suggests that the open patches remained fire-prone after the actual
      climate anomalies. Charcoal identifications indicate that mature rainforest
      patches did persist through the Early to Mid-Holocene climatic transition, the
      subsequent Holocene thermal optimum and the third millennium BP rainforest
      crisis, until 0.8 ka BP. However, disturbance and fragmentation were probably
      more prominent near the boundary of the southern Mayumbe forest. Furthermore, the
      dominance of pioneer and woodland savanna taxa in younger charcoal assemblages
      indicates that rainforest regeneration was hampered by increasingly severe
      drought conditions after 0.8 ka BP. These results support the notion of a dynamic
      forest ecosystem at multicentury time scales across the Central African
      rainforest. 

PMID- 25594741
TI  - Dual-purpose linker for alpha helix stabilization and imaging agent conjugation
      to glucagon-like peptide-1 receptor ligands.
AB  - Peptides display many characteristics of efficient imaging agents such as rapid
      targeting, fast background clearance, and low non-specific cellular uptake.
      However, poor stability, low affinity, and loss of binding after labeling often
      preclude their use in vivo. Using glucagon-like peptide-1 receptor (GLP-1R)
      ligands exendin and GLP-1 as a model system, we designed a novel alpha-helix
      stabilizing linker to simultaneously address these limitations. The stabilized
      and labeled peptides showed an increase in helicity, improved protease
      resistance, negligible loss or an improvement in binding affinity, and excellent
      in vivo targeting. The ease of incorporating azidohomoalanine in peptides and
      efficient reaction with the dialkyne linker enable this technique to potentially
      be used as a general method for labeling alpha helices. This strategy should be
      useful for imaging beta cells in diabetes research and in developing and testing
      other peptide targeting agents. 

PMID- 25594744
TI  - Fast photoinduced reactions in the condensed phase are nonexponential.
AB  - Time-resolved measurements of photoinduced reactions reveal that many ultrafast
      reactions in the femto- to picosecond time scale are nonexponential. In this
      article we provide several examples of reactions that exhibit a nonexponential
      rate. We explain the wide range of the nonexponential reaction by the lack of
      time separation between tau(s), the characteristic fast equilibration time of the
      population in the reactant potential well, and the longer time tau(e), the
      characteristic time to cross the energy barrier between the reactant and the
      product.

PMID- 25594745
TI  - The influence of spatial resolution on human health risk co-benefit estimates for
      global climate policy assessments.
AB  - Assessment of the ability of climate policies to produce desired improvements in
      public health through co-benefits of air pollution reduction can consume
      resources in both time and research funds. These resources increase significantly
      as the spatial resolution of models increases. In addition, the level of spatial
      detail available in macroeconomic models at the heart of climate policy
      assessments is much lower than that available in traditional human health risk
      modeling. It is therefore important to determine whether increasing spatial
      resolution considerably affects risk-based decisions; which kinds of decisions
      might be affected; and under what conditions they will be affected. Human health
      risk co-benefits from carbon emissions reductions that bring about concurrent
      reductions in Particulate Matter (PM10) emissions is therefore examined here at
      four levels of spatial resolution (Uniform Nation, Uniform Region, Uniform
      County/city, Health Risk Assessment) in a case study of Taiwan as one of the
      geographic regions of a global macroeceonomic model, with results that are
      representative of small, industrialized nations within that global model. A
      metric of human health risk mortality (YOLL, years of life lost in life
      expectancy) is compared under assessments ranging from a "uniform simulation" in
      which there is no spatial resolution of changes in ambient air concentration
      under a policy to a "highly spatially resolved simulation" (called here Health
      Risk Assessment). PM10 is chosen in this study as the indicator of air pollution
      for which risks are assessed due to its significance as a co-benefit of carbon
      emissions reductions within climate mitigation policy. For the policy examined,
      the four estimates of mortality in the entirety of Taiwan are 747 YOLL, 834 YOLL,
      984 YOLL and 916 YOLL, under Uniform Taiwan, Uniform Region, Uniform County and
      Health Risk Assessment respectively; or differences of 18%, 9%, 7% if the HRA
      methodology is taken as the baseline. While these differences are small compared
      to uncertainties in health risk assessment more generally, the ranks of different
      regions and of emissions categories as the focus of regulatory efforts estimated
      at these four levels of spatial resolution are quite different. The results
      suggest that issues of risk equity within a nation might be missed by the lower
      levels of spatial resolution, suggesting that low resolution models are suited to
      calculating national cost-benefit ratios but not as suited to assessing co
      benefits of climate policies reflecting intersubject variability in risk, or in
      identifying sub-national regions and emissions sectors on which to focus
      attention (although even here, the errors introduced by low spatial resolution
      are generally less than 40%). 

PMID- 25594746
TI  - Adaptation in hindsight: dynamics and drivers shaping urban wastewater systems.
AB  - Well-planned urban infrastructure should meet critical loads during its design
      lifetime. In order to proceed with design, engineers are forced to make numerous
      assumptions with very little supporting information about the development of
      various drivers. For the wastewater sector, these drivers include the future
      amount and composition of the generated wastewater, effluent requirements,
      technologies, prices of inputs such as energy or chemicals, and the value of
      outputs produced such as nutrients for fertilizer use. When planning wastewater
      systems, there is a lack of methods to address discrepancies between the
      timescales at which fundamental changes in these drivers can occur, and the long
      physical life expectancy of infrastructure (on the order of 25-80 years). To
      explore these discrepancies, we take a hindsight perspective of the long-term
      development of wastewater infrastructure and assess the stability of assumptions
      made during previous designs. Repeatedly we find that the drivers influencing
      wastewater loads, environmental requirements or technological innovation can
      change at smaller timescales than the infrastructure design lifetime, often in
      less than a decade. Our analysis shows that i) built infrastructure is
      continuously confronted with challenges it was not conceived for, ii) significant
      adaptation occurs during a structure's lifetime, and iii) "muddling-through" is
      the pre-dominant strategy for adaptive management. As a consequence, we argue,
      there is a need to explore robust design strategies which require the systematic
      use of scenario planning methods and instruments to increase operational,
      structural, managerial, institutional and financial flexibility. Hindsight
      studies, such as this one, may inform the development of robust design strategies
      and assist in the transition to more explicit forms of adaptive management for
      urban infrastructures. 

PMID- 25594743
TI  - Open pipelines for integrated tumor genome profiles reveal differences between
      pancreatic cancer tumors and cell lines.
AB  - We describe open, reproducible pipelines that create an integrated genomic
      profile of a cancer and use the profile to find mutations associated with disease
      and potentially useful drugs. These pipelines analyze high-throughput cancer
      exome and transcriptome sequence data together with public databases to find
      relevant mutations and drugs. The three pipelines that we have developed are: (1)
      an exome analysis pipeline, which uses whole or targeted tumor exome sequence
      data to produce a list of putative variants (no matched normal data are needed);
      (2) a transcriptome analysis pipeline that processes whole tumor transcriptome
      sequence (RNA-seq) data to compute gene expression and find potential gene
      fusions; and (3) an integrated variant analysis pipeline that uses the tumor
      variants from the exome pipeline and tumor gene expression from the transcriptome
      pipeline to identify deleterious and druggable mutations in all genes and in
      highly expressed genes. These pipelines are integrated into the popular Web
      platform Galaxy at http://usegalaxy.org/cancer to make them accessible and
      reproducible, thereby providing an approach for doing standardized, distributed
      analyses in clinical studies. We have used our pipeline to identify similarities
      and differences between pancreatic adenocarcinoma cancer cell lines and primary
      tumors. 

PMID- 25594747
TI  - C5-epimerase and 2-O-sulfotransferase associate in vitro to generate contiguous
      epimerized and 2-O-sulfated heparan sulfate domains.
AB  - Heparan sulfate (HS), a complex polysaccharide of the cell surface, is endowed
      with the remarkable ability to bind numerous proteins and, as such, regulates a
      large variety of biological processes. Protein binding depends on HS structure;
      however, in the absence of a template driving its biosynthesis, the mechanism by
      which protein binding sequences are assembled remains poorly known. Here, we
      developed a chemically defined 13C-labeled substrate and NMR based experiments to
      simultaneously follow in real time the activity of HS biosynthetic enzymes and
      characterize the reaction products. Using this new approach, we report that the
      association of C5-epimerase and 2-O-sulfotransferase, which catalyze the
      production of iduronic acid and its 2-O-sulfation, respectively, is necessary to
      processively generate extended sequences of contiguous IdoA2S-containing
      disaccharides, whereas modifications are randomly introduced when the enzymes are
      uncoupled. These data shed light on the mechanisms by which HS motifs are
      generated during biosynthesis. They support the view that HS structure assembly
      is controlled not only by the availability of the biosynthetic enzymes but also
      by their physical association, which in the case of the C5-epimerase and 2-O
      sulfotransferase was characterized by an affinity of 80 nM as demonstrated by
      surface plasmon resonance experiments.

PMID- 25594748
TI  - Identification of novel interactors of human telomeric G-quadruplex DNA.
AB  - A chemoproteomic-driven approach was used to investigate the interaction network
      between human telomeric G-quadruplex DNA and nuclear proteins. We identified
      novel G-quadruplex binding partners, able to recognize these DNA structures at
      chromosome ends, suggesting a possible, and so far unknown, role of these
      proteins in telomere functions. 

PMID- 25594749
TI  - Hydrogen bonding in aprotic solvents, a new strategy for gelation of bioinspired
      catecholic copolymers with N-isopropylamide.
AB  - Copolymers of N-isopropylacrylamide (NIPAM) and dopamine methacrylate can
      establish a reversible, self-healing 3D network in aprotic solvents based on
      hydrogen bonding. The reactivity and hydrogen bonding formation of catechol
      groups in copolymer chains are studied by UV-vis and (1) H NMR spectroscopy,
      while reversibility from sol to gel and inverse as well as self-healing
      properties are tested rheologically. The produced reversible organogel can self
      encapsulate physically interacting or chemically bonded solutes such as drugs due
      to thermosensitivity of the used copolymer. This system offers dual-targeted and
      controlled drug delivery and release-by slowing down release kinetics by
      supramolecular bonding of the drug and by reducing diffusion rates due to modulus
      increase. 

PMID- 25594751
TI  - [Gastroenterology Society of Peru 2013-2014: achievements and challenges].

PMID- 25594752
TI  - [Molecular characterization of hereditary colorectal cancer in Peru].
AB  - OBJECTIVE: To investigate the molecular deficiency in MMR genes associated to
      Lynch syndrome. MATERIAL AND METHODS: Immunohistochemical and microsatellite
      instability (MSI) analysis were performed in 5 families with suspected Lynch
      syndrome according to the clinical criteria, Amsterdam and/or Bethesda that had
      been treated at the Hospital Nacional Almanzor Aguinaga Asenjo (Lambayeque-Peru)
      during 2007-2010. RESULTS: The absence of expression of MLH1/PMS2 and high MSI
      (MSI-H) were observed in a male patient aged 60 with adenocarcinoma grade I. In
      addition, the point mutational analysis was performed in BRAF (V600E) to rule
      that it is a sporadic case of colorectal cancer. The absence of mutation in BRAF
      together with the molecular analysis suggests the suspicion as a Lynch syndrome.
      CONCLUSIONS: It is the first molecular study reported in the Peruvian population
      and demonstrates the importance of molecular analysis in families with suspected
      hereditary colorectal cancer in order to provide possibilities of surveillance
      and monitoring that have been shown to reduce morbidity and mortality of
      colorectal cancer in the Peruvian population.

PMID- 25594753
TI  - [The most common rheumatic diseases in patients with autoimmune liver disease in
      the Hospital Arzobispo Loayza from 2008-2013, Lima, Peru].
AB  - OBJECTIVE: To identify the most common autoimmune rheumatic diseases in patients
      with autoimmune liver disease in the Hospital Arzobispo Loayza (HAL) from 2008 
      2013. MATERIALS AND METHODS: This is a transversal and descriptive study, we
      analyzed 125 medical records, only 86 patients fulfill the diagnostic criteria
      for autoimmune liver disease, of whom 46 had diagnosis of autoimmune
      hepatitis(AIH), 39 primary biliary cirrhosis(PBC) and just 1 primary sclerosing
      cholangitis (PSC). In our study group we looked for the clinical and laboratory
      characteristics most common and the frequency of cases in the HAL. RESULTS: Of
      the 46 patients with AIH, 16 (34.78%) were diagnosed with autoimmune rheumatic
      disease concurrence. Of these, 7 (15.22%) patients had Sjogren I?s Disease (SD),
      6 (13.04%) had systemic lupus erythematosus (SLE) and 3 (6.52%) had rheumatoid
      arthritis (RA). We found 39 patients with PBC, 18 (46.15%) had other associated
      extrahepatic autoimmune disease, of whom 12 (30.77%) had SD, 3 (7.69%) SLE and 3
      (7.69%) RA. One patient had the diagnosis of PSC, a sixty year old woman that had
      no concurrence with rheumatic disease. CONCLUSIONS: In our study was found that
      SD is the most common rheumatic disease in patients with AIH and PBC, followed by
      SLE and RA, with autoimmune liver disease with rheumatic symptoms and vice versa.

PMID- 25594754
TI  - [Clinicopathologic characteristics of the pancreatic cystic tumors].
AB  - Formerly an infrequent pathology, pancreatic cystic tumors stand nowadays for 25%
      of all pancreatic surgical diseases. OBJECTIVE: Evaluate the frequency of the
      presentation of each type and the behavior of the pancreatic cystic tumors that
      went to surgery in our unit. MATERIALS AND METHODS: In our Pancreas Unit, 708
      patients with pancreatic tumors underwent surgery in the period between October
      2002 and December 2013. 146 cases of pancreatic cystic tumors taken from that
      group are the topic of the present study. RESULTS: Even when diagnosing
      pancreatic tumors as cystic tumors was possible in 91% of cases during pre-op
      evaluation, categorizing the type of cystic tumor was only possible in 73% of
      cases. In 128 cases (88%), cystic tumors were removable. Due to advanced disease,
      in 3 cases only diversion surgery was possible and, in 15 cases, exploration and
      biopsy was the only choice. When the frequency of malignancy was assessed for all
      four types of pancreatic cystic tumors, the one most frequently becoming
      malignant was mucinous papillary intraductal (53%), followed by mucinous cystic
      (50%). Solid pseudopapillary pancreatic cystic tumors became malignant in 29% of
      cases and for serous cystoadenoma the frequency of malignancy was nihil.
      CONCLUSIONS: Cystic tumors are the most frequent type of pancreatic lesion. It's
      of paramount importance to categotize them since risk of malignancy can be as
      high as 52% in case of mucinous intraductal papillary type.

PMID- 25594755
TI  - [Addition of bismuth subsalicylate to triple eradication therapy for Helicobacter
      pylori infection: efficiency and adverse events].
AB  - OBJECTIVES: To establish the efficiency and adverse effects of the addition of
      bismuth subsalicylate to triple eradication therapy for Helicobacter pylori
      infection. MATERIAL AND METHODS: Double blind controlled experimental trial. The
      study population consisted of 54 patients with Helicobacter pylori infection: 29
      were allocated to the experimental group, who received the usual triple plus
      bismuth subsalicylate therapy, and 24 received the triple therapy plus placebo.
      RESULTS: The average age was 47+-14.9 years, 66.7% of the patients were women.
      Both groups underwent the breath test: it was negative in 89.7% of the patients
      from the experimental group and 80% of the patients from the placebo group
      (p=0.319). The adverse events of both groups were: diarrhea (10.3% in the
      experimental group vs 16% in the placebo group; p=0.537), dark feces (37.9% in
      the experimental group vs 0% in the placebo group; p=0.001), abdominal pain
      (20.7% in the experimental group vs 52% in the placebo group; p=0.016). Nausea
      only were present in 3% of the patients of placebo group p=0.055). CONCLUSIONS:
      The association of bismuth subsalicylate to the triple therapy scheme for the
      eradication of Helicobacter pylori was effective in 89.7% of patients, whereas
      80% of efficiency in the experimental group.

PMID- 25594756
TI  - "Leopard skin sign": the use of narrow-band imaging with magnification endoscopy
      in celiac disease.
AB  - Celiac Disease (CD) is an immune reaction to gluten containing foods such as rye,
      wheat and barley. This condition affects individuals with a genetic
      predisposition; it targets the small bowel and may cause symptoms including
      diarrhea, malabsorption, weight loss, abdominal pain and bloating. The diagnosis
      is made by serologic testing of celiac-specific antibodies and confirmed by
      histology. Certain endoscopic characteristics, such as scalloping, reduction in
      the number of folds, mosaic-pattern mucosa or nodular mucosa, are suggestive of
      CD and can be visualized under white light endoscopy. Due to its low sensitivity,
      endoscopy alone is not recommended to diagnose CD; however, enhanced visual
      identification of suspected mucosal abnormalities through the use of new
      technologies, such as narrow band imaging with magnification (NBI-ME), could
      assist in targeting biopsies and thereby increasing the sensitivity of endoscopy.
      This is a case series of seven patients with serologic and histologic diagnoses
      of CD who underwent upper endoscopies with NBI-ME imaging technology as part of
      their CD evaluation. By employing this imaging technology, we could identify
      patchy atrophy sites in a mosaic pattern, with flattened villi and alteration of
      the central capillaries of the duodenal mucosa. We refer to this epithelial
      pattern as "Leopard Skin Sign". Since epithelial lesions are easily seen using
      NBI-ME, we found it beneficial for identifying and targeting biopsy sites. Larger
      prospective studies are warranted to confirm our findings. 

PMID- 25594757
TI  - [Endoscopy training by using ex vivo and simulators: a new teaching tool].
AB  - In recent decades, the traditional teaching model of gastrointestinal endoscopy
      has been based on the teacher-student tutorial method based on theoretical
      models. Today, simulators have the advantages of virtual reality. The handling
      apparatus is similar to that used in clinical practice; it is safe, which allows
      unlimited use, cost-effective for institutions and with superior performance over
      other training models. Besides, biological simulators are a viable, accessible
      and affordable tool to simulate gastrointestinal lesions, allowing training in
      endoscopy with a high degree of similarity in the endoscopic appearance. In this
      review, we analyze both models, showing its advantages for the training of the
      endoscopist of the times. 

PMID- 25594758
TI  - [Collagenous sprue: secondary or independent from celiac disease?].
AB  - Collagenous sprue is a rare disease that goes with persistent diarrhea, weight
      loss and bad absortion, because it affects the small intestine, mainly duodenum
      and proximal jejunum. Diagnosis is made by having clinical signs and histological
      proof of atrophy and subepitelial deposit of collagenous material. Its etiology
      is not known completely, it is proposed that the origin is autoimmune because its
      relationship with celiac disease. Also there is a proposal that is a celiac
      evolution to gluten free diet. Is because this is not clear that we present a
      case of a patient with bad absorptive diarrhea and a clinical expression of
      collagenous sprue, that had a great clinical response to corticosteroids with
      home parenteral nutrition center. 

PMID- 25594759
TI  - [Crohn's disease: clinical case and review of the literature].
AB  - We present a 15 year male patient with more than 2 years of clinical symptoms.
      Patient has abdominal pain with episodes of partial intestinal occlusion,
      recurrent diarrhea, weight loss and fever. Lab findings were PCR: 92, 17:
      albumine: 3,2 gr/dl, microcitic hipocromic anemia (10 gr%). Hepatoesplenomegaly
      in the Echo in TAC there was a thickness of the distal ileum and right colon with
      free liquid in the abdominal cavity. Intestinal transit: Stenosis of the distal
      ileum. In a colonoscopy: ulcers in the right colon with biopsies that suggest
      Crohn disease. Endoscopic capsule: ulcerative ileitis. The patient was discharged
      with prednisone and azatioprine but because there were new episodes of intestinal
      occlusion surgery was decided. The outcome was good and in the post surgery
      treatment Infliximab was used. We discuss medical and surgical treatment options.

PMID- 25594760
TI  - [Plasmablastic lymphoma: a case of rectal disease with bone marrow involvement in
      a HIV positive patient].
AB  - Plasmablastic lymphoma is an aggressive form of lymphoma diffuse large B cell
      Lymphoma, initially described in HIV positive patients associated with lesions in
      the oral cavity. It is about 2% of NHL associated with HIV. This entity currently
      represents a challenge for the diagnosis and treatment, showing a poor long-term
      prognosis. This report describes a patient with VIH on HAART and CD4 count in 490
      cells/ml associated with Plasmablastic lymphoma that involves rectum and bone
      marrow. The patient received 6 cycles of EPOCH regimen with complete response. 

PMID- 25594762
TI  - Cyclosporine A and tacrolimus inhibit urothelial tumorigenesis.
AB  - The functional role of nuclear factor of activated T-cells (NFAT), while it has
      been extensively investigated in the immune system, remains uncertain in bladder
      cancer development. We here aim to assess the effects of cyclosporine A (CsA) and
      tacrolimus (FK506), immunosuppressants known to specifically inactivate the NFAT
      pathway in immune cells, on neoplastic transformation of urothelial cells.
      Immunohistochemistry revealed that the expression levels of NFATc1, a NFAT
      isoform shown to function as an oncogene in a sarcoma model, were elevated in
      urothelial neoplasms, compared with non-neoplastic urothelial tissues, and in low
      grade and high-grade papillary urothelial carcinomas, compared with papillary
      urothelial neoplasms of low malignant potential. In an immortalized normal
      urothelial cell line SVHUC, CsA and FK506 reduced NFATc1 expression, NFAT
      transcriptional activity, and the expression of c-myc, a downstream target of
      NFATc1 signals. Treatment with CsA or FK506 in the SVHUC cells undergoing
      neoplastic transformation induced by exposure to a chemical carcinogen 3
      methylcholanthrene resulted in strong inhibition in colony formation in vitro as
      well as tumor formation in NOD-SCID mice. CsA and FK506 were additionally found
      to up-regulate the expression of several molecules that play a protective role in
      bladder tumorigenesis, including p53, p21, and p27, and down-regulate that of
      oncogenic genes, such as cyclin D1, cyclin D3, and cyclin E, in SVHUC cells with
      the carcinogen challenge. Thus, CsA and FK506 likely inhibit urothelial
      tumorigenesis. These findings offer a potential chemopreventive approach for
      urothelial tumors using NFAT inhibitors.

PMID- 25594763
TI  - Exfoliation syndrome: a disease with an environmental component.
AB  - PURPOSE OF REVIEW: Exfoliation syndrome (XFS), the most common cause of secondary
      open angle glaucoma, is associated with significant ocular morbidity. Recent
      studies have pointed toward environmental components that may alter the risk of
      XFS development. This review focuses on the recent studies elucidating the role
      of environmental factors that play a role in the development of exfoliation
      syndrome. RECENT FINDINGS: In XFS, aberrant microfibril formation emanating from
      the cell-extracellular matrix interface admixes with other macromolecules and is
      cross-linked by lysyl oxidase like 1 (LOXL1) activity. A common gene variant in
      the LOXL1 enzyme, an enzyme critical for enhancing the tensile strength of
      collagen and elastin in extracellular matrices, has been found in approximately
      90% of XFS cases. However, approximately 80% of controls also have disease
      associated LOXL1 gene variants. These findings point toward other nongenetic
      factors influencing the development of XFS. Increasing latitude, solar radiation,
      climatic variables and dietary factors such as high coffee consumption and low
      dietary folate intake are among the nongenetic factors associated with increased
      risk of XFS. SUMMARY: A greater understanding of the environmental components
      associated with XFS may lead to lifestyle preventive strategies to ameliorate
      disease burden.

PMID- 25594764
TI  - Update on pseudoexfoliation syndrome pathogenesis and associations with
      intraocular pressure, glaucoma and systemic diseases.
AB  - PURPOSE OF REVIEW: Pseudoexfoliation (PEX) syndrome is a common age-related
      disorder affecting intraocular and extraocular tissues. This review focuses on
      recent publications related with the pathogenesis and associations of PEX
      syndrome with intraocular pressure (IOP), glaucoma and systemic diseases. RECENT
      FINDINGS: In PEX tissues, expression of lysyl oxidase-like 1 (LOXL1) was found to
      be markedly dysregulated. This may adversely affect elastin metabolism and lead
      to elastotic alteration in tissues such as lamina cribrosa. There is increasing
      evidence that cellular stress conditions and low-grade chronic inflammatory
      processes are involved in the pathogenesis of PEX. Although there is an increased
      risk for glaucoma development in patients with PEX and ocular hypertension as
      compared with non-PEX patients with ocular hypertension, LOXL1 single nucleotide
      polymorphisms were not associated with intraocular pressure (IOP) differences.
      Lack of association of PEX with all-cause mortality or dementia has been reported
      recently. The association with vascular diseases is not consistent among
      different studies. SUMMARY: Despite the high prevalence of the LOXL1 variants in
      the general population, a much lower proportion of the population develops PEX,
      suggesting that in addition to LOXL1, other genetic, epigenetic and environmental
      factors may contribute to the development of PEX. Also, LOXL1 cannot help to
      identify those with PEX at increased risk for glaucoma development. Increased
      risk for glaucoma development in PEX patients who present with increased IOP may
      be related to other factors beyond IOP, contributing to increased vulnerability
      of the optic nerve to glaucoma development in the presence of PEX.

PMID- 25594765
TI  - Medical therapy for glaucoma: what to add after a prostaglandin analogs?
AB  - PURPOSE OF REVIEW: Prostaglandin analogs (PGAs) are the most widely used ocular
      hypotensive medications. Half of the patients with glaucoma and 40% of patients
      with ocular hypertension require more than one medication to sufficiently lower
      their intraocular pressures (IOPs). Therefore, it is important to understand the
      varying efficacy of adjunctive therapies currently available for use in
      combination with PGAs. RECENT FINDINGS: The IOP-lowering efficacy and safety
      profiles of various adjunctive treatments continue to be better elucidated,
      including the nocturnal IOP-lowering efficacy of various medication classes and
      laser trabeculoplasty. SUMMARY: For patients already on a PGA, the mean diurnal
      IOP-lowering achieved with the addition of an alpha2 adrenergic agonist, a beta
      adrenergic antagonist, or a topical carbonic anhydrase inhibitor is similar,
      whereas the side-effect profiles, nocturnal IOP-lowering efficacy, and trough IOP
      lowering effects vary. Laser trabeculoplasty is also an effective means of
      further lowering the IOP in patients on a PGA.

PMID- 25594767
TI  - Measuring intraocular pressure.
AB  - PURPOSE OF REVIEW: Tonometry is undergoing a long-overdue renaissance. Goldmann
      applanation tonometry (GAT) is 50-year-old technology. Although GAT is considered
      a 'reference standard', it has many limitations and confounders. This review
      compares GAT to some of the newer technologies that have recently been
      commercialized or are in development. RECENT FINDINGS: Dynamic contour tonometry
      is fairly cornea-independent, but requires technical skill to carry out. Rebound
      tonometry requires no anesthetic and is particularly useful in children. The
      ocular response analyzer quantifies corneal biomechanical factors and provides
      other useful measures relevant to glaucoma risk. A transpalpebral tonometer that
      claims to measure intraocular pressure (IOP) through the closed eyelid has been
      introduced, but studies comparing it to conventional tonometers suggest it is too
      unreliable for routine use. Various new technologies including IOP-sensing
      contact lenses and implantable sensors are in clinical evaluation. SUMMARY: There
      is no perfect tonometer, and clinicians must choose which to use in their daily
      practice, balancing accuracy, precision, convenience, and cost. Clinicians should
      recognize that a single IOP measurement is but an often error-prone snapshot of a
      widely varying physiologic parameter. IOP data should only be used in the context
      of the overall clinical picture.

PMID- 25594766
TI  - New developments in optical coherence tomography.
AB  - PURPOSE OF REVIEW: Optical coherence tomography (OCT) has become the cornerstone
      technology for clinical ocular imaging in the past few years. The technology is
      still rapidly evolving with newly developed applications. This manuscript reviews
      recent innovative OCT applications for glaucoma diagnosis and management. RECENT
      FINDINGS: The improvements made in the technology have resulted in increased
      scanning speed, axial and transverse resolution, and more effective use of the
      OCT technology as a component of multimodal imaging tools. At the same time, the
      parallel evolution in novel algorithms makes it possible to efficiently analyze
      the increased volume of acquired data. SUMMARY: The innovative iterations of OCT
      technology have the potential to further improve the performance of the
      technology in evaluating ocular structural and functional characteristics and
      longitudinal changes in glaucoma.

PMID- 25594768
TI  - Desensitizing efficacy of nano-carbonate apatite dentifrice and Er,Cr:YSGG laser:
      a randomized clinical trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the desensitizing effects of a
      dentifrice containing nano-carbonate apatite (n-CAP) and Er,Cr:YSGG laser in the
      treatment of dentin hypersensitivity. BACKGROUND DATA: Most studies of
      hypersensitivity treatment have been conducted with different methods of
      professional treatment and self-care in each study. Moreover, clinical studies
      that compare self-care and professional treatment have not yet been published.
      METHODS: Eighty-two patients with dentin hypersensitivity were divided randomly
      into three groups: (1) a control group with strontium chloride dentifrice (SC),
      (2) n-CAP dentifrice (n-CAP), and (3) an Er,Cr:YSGG laser (laser) group. The
      study was conducted for 4 weeks: a treatment period of 2 weeks and a maintenance
      period of 2 subsequent weeks. The SC and n-CAP groups were instructed to brush
      their teeth twice a day for 1 min. The laser group visited twice at 1 week
      intervals for irradiation of the sensitive teeth. The desensitizing effect was
      evaluated by assessing the tactile sensitivity using the visual analogue scale
      (VAS), and evaporative air sensitivity was determined using an air blast score
      (ABS). RESULTS: The n-CAP group and the laser group showed significantly
      different desensitizing effects in VAS after 4 weeks (69% and 63%, respectively)
      and a 33% (p<0.05) and 3% (p>0.05) desensitizing effect, respectively, in VAS
      during the maintenance period. CONCLUSIONS: The n-CAP and the laser were
      effective in reducing dentin hypersensitivity. The laser had a superior
      desensitizing effect at the initial stage, whereas the n-CAP maintained its
      effect for a relatively longer time in clinical situations.

PMID- 25594770
TI  - Intense pulsed light treatment for dry eye disease due to meibomian gland
      dysfunction; a 3-year retrospective study.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical benefits of
      intense-pulsed-light therapy for the treatment of dry-eye disease caused by
      meibomian gland dysfunction (MGD). BACKGROUND DATA: MGD is the leading cause of
      evaporative dry eye disease. It is currently treated with a range of methods that
      have been shown to be only somewhat effective, leading to the need for advanced
      treatment options. METHODS: A retrospective noncomparative interventional case
      series was conducted with 91 patients presenting with severe dry eye syndrome.
      Treatment included intense-pulsed-light therapy and gland expression at a single
      outpatient clinic over a 30-month study. Pre/post tear breakup time data were
      available for a subset of 78 patients. For all patients, a specially developed
      technique for the treatment of dry eye syndrome was applied as a series of
      monthly treatments until there was adequate improvement in dry eye syndrome
      symptoms by physician judgment, or until patient discontinuation. RESULTS:
      Primary outcomes included change in tear breakup time, self-reported patient
      satisfaction, and adverse events. Physician-judged improvement in dry eye tear
      breakup time was found for 68 of 78 patients (87%) with seven treatment visits
      and four maintenance visits on average (medians), and 93% of patients reported
      post-treatment satisfaction with degree of dry eye syndrome symptoms. Adverse
      events, most typically redness or swelling, were found for 13% of patients. No
      serious adverse events were found. CONCLUSIONS: Although preliminary, study
      results of intense-pulsed-light therapy treatment for dry eye syndrome caused by
      meibomian gland dysfunction are promising. A multisite clinical trial with a
      larger sample, treatment comparison groups, and randomized controlled trials is
      currently underway.

PMID- 25594771
TI  - Ferroelectric 180 degrees  domain wall motion controlled by biaxial strain.
AB  - 180 degrees  domain wall motion in a tetragonal ferroelectric oxide is
      accelerated by an order of magnitude using in situ strain in a force microscope.
      Single-domain PbZr0.2 Ti0.8 O3 films on piezoelectric (001)-oriented 0.72PbMg1/3
      Nb2/3 O3 -0.28PbTiO3 substrates allow for direct investigation of strain
      dependent domain dynamics. The strain effect depends on the sign of applied field
      through strain-dependent electrode built-in potentials and a suggested charging
      of tilted walls. 

PMID- 25594772
TI  - Selective removal of carious human dentin using a nanosecond pulsed laser
      operating at a wavelength of 5.85 MUm.
AB  - Less invasive methods for treating dental caries are strongly desired. However,
      conventional dental lasers do not always selectively remove caries or ensure good
      bonding to the composite resin. According to our previous study, demineralized
      dentin might be removed by a nanosecond pulsed laser operating at wavelengths of
      around 5.8 MUm . The present study investigated the irradiation effect of the
      light on carious human dentin classified into "remove," "not remove," and
      "unclear" categories. Under 5.85-MUm laser pulses, at average power densities of
      30 W/cm2 and irradiation time of 2 s, the ablation depth of "remove" and "not
      remove," and also the ablation depth of "unclear" and "not remove," were
      significantly different (p<0.01 ). The ablation depth was correlated with both
      Vickers hardness and Ca content. Thus, a nanosecond pulsed laser operating at
      5.85  MUm proved an effective less-invasive caries treatment.

PMID- 25594769
TI  - Histomorphometric evaluation of the effects of various diode lasers and force
      levels on orthodontic mini screw stability.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of different
      laser dose and force levels on the stability of orthodontic mini screws used for
      anchorage, by histomorphometric analyses. BACKGROUND DATA: Low-level laser
      therapy speeds up blood flow, improves the mechanism of the revitalization
      processes, reduces the risk of infection, boosts metabolic activities, and
      accelerates the healing of the damaged tissue. Although there are many research
      studies about low-level laser therapy applications in a variety of areas, no
      investigations were found concerning mini screw stability using various laser
      dose levels with different force level applications. METHODS: Seventeen New
      Zealand white rabbits were used. A total of 68 cylindrical, self-drilling
      orthodontic mini screws were threaded at the fibula. Experimental subjects were
      divided into six groups; force application was not performed in the first three
      groups, whereas 150 g of force was applied via nickel-titanium closed-coil
      springs placed between two mini screws in the other three groups. Measurements of
      the initial torque values (10 Ncm) were manipulated by a digital portable torque
      gauge. Various low-level laser doses were applied to the groups during the
      postoperative 10 days. After 4 weeks, bone-to-implant contact and cortical bone
      thickness were histomorphometrically analyzed. RESULTS: In the 150 g force plus
      20 J/cm(2) dosage group, the highest bone-to-implant contact values were
      observed. (p<0.05) There were no statistically significant correlations between
      cortical bone thickness and bone-to-implant contact values; on the other hand, no
      significant difference was found among the same groups in terms of cortical bone
      thickness values (p>0.05). CONCLUSIONS: Low-level laser therapy was noticed to
      induce the mini screw-bone contact area. Low-level laser therapy may be a
      supplementary treatment method to increase the stability of the orthodontic mini
      screw.

PMID- 25594773
TI  - Competitive protein adsorption to soft polymeric layers: binary mixtures and
      comparison to theory.
AB  - Nanoparticles immersed in biological fluids readily adsorb proteins. The protein
      corona thus generated on the surface of the particles largely determines their
      biological fate. Since biological fluids, e.g., blood plasma, contain a large
      number of proteins, competitive adsorption must be considered. We study the
      competitive adsorption of lysozyme, cytochrome c, papain, and RNase A onto a soft
      charged polymeric layer. The experimental data of binary protein mixtures are
      compared to a theoretical model taking into account electrostatic and hydrophobic
      interactions between the proteins and the network. The interactions between bound
      proteins are modeled within a second virial approximation. The model possesses
      full generality and can be applied to the adsorption of an arbitrary number of
      protein types. The parameters describing the adsorption of a single protein type
      are obtained by isothermal titration calorimetry (ITC), while the competitive
      adsorption of a binary mixture is studied by fluorescence spectroscopy. The
      competitive adsorption can be predicted from the data related to the adsorption
      of the single types without adjustable parameters. 

PMID- 25594774
TI  - Multilayer graphitic coatings for thermal stabilization of metallic
      nanostructures.
AB  - We demonstrate that graphitic coatings, which consist of multilayer disordered
      graphene sheets, can be used for the thermal protection of delicate metal
      nanostructures. We studied cobalt slanted nanopillars grown by glancing angle
      deposition that were shown to melt at temperatures much lower than the melting
      point of bulk cobalt. After graphitic coatings were conformally grown over the
      surfaces of Co nanopillars by chemical vapor deposition, the resulting carbon
      coated Co nanostructures retained their morphology at elevated temperatures,
      which would damage the uncoated structures. Thermal stabilization is also
      demonstrated for carbon-coated Ti nanopillars. The results of this study may be
      extended to other metallic and possibly even nonmetallic nanostructures that need
      to preserve their morphology at elevated temperatures in a broad range of
      applications. 

PMID- 25594775
TI  - Psychoeducation for relapse prevention in bipolar disorder: a systematic review
      of efficacy in randomized controlled trials.
AB  - OBJECTIVES: Previous reviews have concluded that interventions including
      psychoeducation are effective in preventing relapse in bipolar disorder, but the
      efficacy of psychoeducation itself has not been systematically reviewed. Our aim
      was to evaluate the efficacy of psychoeducation for bipolar disorder in
      preventing relapse and other outcomes, and to identify factors that relate to
      clinical outcomes. METHODS: We employed the systematic review of randomized
      controlled trials of psychoeducation in participants with bipolar disorder not in
      an acute illness episode, compared with treatment-as-usual, and placebo or active
      interventions. Pooled odds ratios (ORs) for non-relapse into any episode,
      mania/hypomania, and depression were calculated using an intent-to-treat (ITT)
      analysis, assigning dropouts to relapse, with a sensitivity analysis in which
      dropouts were assigned to non-relapse (optimistic ITT). RESULTS: Sixteen studies
      were included, eight of which provided data on relapse. Although heterogeneity in
      the data warrants caution, psychoeducation appeared to be effective in preventing
      any relapse [n = 7; OR: 1.98-2.75; number needed to treat (NNT): 5-7, depending
      on the method of analysis] and manic/hypomanic relapse (n = 8; OR: 1.68-2.52;
      NNT: 6-8), but not depressive relapse. Group, but not individually, delivered
      interventions were effective against both poles of relapse; the duration of
      follow-up and hours of therapy explained some of the heterogeneity.
      Psychoeducation improved medication adherence and short-term knowledge about
      medication. No consistent effects on mood symptoms, quality of life, or
      functioning were found. CONCLUSIONS: Group psychoeducation appears to be
      effective in preventing relapse in bipolar disorder, with less evidence for
      individually delivered interventions. Better understanding of mediating
      mechanisms is needed to optimize efficacy and personalize treatment.

PMID- 25594776
TI  - Current Practice and Outcomes of Thoracoscopic Esophageal Atresia and
      Tracheoesophageal Fistula Repair: A Multi-institutional Analysis in Japan.
AB  - BACKGROUND: In order to better understand the current practice and outcomes of
      thoracoscopic repair of esophageal atresia (EA)/tracheoesophageal fistula (TEF),
      a multi-institutional analysis was conducted among seven Japanese institutes.
      MATERIALS AND METHODS: A survey was sent to the seven institutes regarding the
      surgical technique, postoperative management, and outcomes of thoracoscopic
      repair of EA/TEF. RESULTS: The operation was uniformly performed via an
      intrapleural approach in the 0-45 degrees  prone position. The TEF was occluded
      with suture ligature in four (57.1%) institutes and clips in the remaining three
      (42.9%) institutes. Anastomosis was performed using the extracorporeal knot-tying
      technique in four institutes and the intracorporeal technique in three
      institutes. Patients were routinely left intubated and paralyzed for 3-7 days
      postoperatively in four institutes. In total, 58 patients underwent thoracoscopic
      repair of EA/TEF. Fifty-two (89.7%) of the patients underwent successful
      thoracoscopic repair. Six (10.3%) operations were converted to open thoracotomy
      because of a long gap (n=4), right aortic arch (n=1), and intraoperative
      instability (n=1). The body weight at operation ranged from 1.2 to 4.6 kg, and
      the operative time ranged from 115 to 428 minutes. There were no major
      intraoperative complications. Eleven patients (19.0%) suffered from anastomotic
      leakage. Twenty-eight patients (48.3%) developed anastomotic stricture. One
      patient died during the postoperative period because of an unrelated disease.
      Recurrent TEF developed in three patients (5.2%). Thirteen patients (22.4%) later
      required fundoplication. CONCLUSIONS: The outcome of thoracoscopic repair of
      EA/TEF was comparable to that of the open procedure. As considerable variability
      was observed among the seven institutes with respect to the surgical technique
      and management, standardizing the surgical management may improve the outcome.

PMID- 25594777
TI  - Prevalence and Clinical Effects of Certain Therapy Concepts among Partially
      Edentulous Serbian Elderly.
AB  - PURPOSE: This study was conducted to identify the prevalence of partially
      edentulous individuals in Serbia and to identify prosthodontic treatment used for
      their rehabilitation as well as to compare prosthodontic treatment concepts among
      Serbian elderly participants who answered closed-format questionnaires. MATERIALS
      AND METHODS: The study was conducted at the Clinic for Dental Prosthetics,
      University of Belgrade, Military Medical Academy and the Department of
      Prosthodontics of Home Centre Belgrade; the study consisted of 120 participants.
      A questionnaire with closed-format questions regarding the influence of applied
      therapy concepts for participants with Kennedy Class I partial edentulism was
      created. Statistical software SPSS 11.5 was used for data analysis. Chi-square
      tests were performed, and p-values were calculated for each parameter. RESULTS: A
      total of 1081 people were examined; 730 participants were partially edentulous in
      at least one jaw. Five hundred forty-one participants wore Kennedy Class I
      maxillary or mandibular removable partial dentures (RPDs). Ninety percent of the
      patients were restored with RPDs; 60% of participants were unrestored, had
      shortened dental arches, and requested alternative therapeutic solutions.
      Significantly lower needs for new treatments were identified in participants with
      fixed dental prostheses (7.5%). CONCLUSIONS: Kennedy Class I was the most common
      type of partial edentulism among Serbian elderly, usually treated with RPDs.
      Elderly participants with the applied shortened dental arch and RPD therapy
      concepts requested alternative therapeutic solutions more often than those
      rehabilitated with fixed partial dentures.

PMID- 25594779
TI  - Dynamic mathematical modelling of the removal of hydrophilic VOCs by biotrickling
      filters.
AB  - A mathematical model for the simulation of the removal of hydrophilic compounds
      using biotrickling filtration was developed. The model takes into account that
      biotrickling filters operate by using an intermittent spraying pattern. During
      spraying periods, a mobile liquid phase was considered, while during non-spraying
      periods, a stagnant liquid phase was considered. The model was calibrated and
      validated with data from laboratory- and industrial-scale biotrickling filters.
      The laboratory experiments exhibited peaks of pollutants in the outlet of the
      biotrickling filter during spraying periods, while during non-spraying periods,
      near complete removal of the pollutant was achieved. The gaseous outlet emissions
      in the industrial biotrickling filter showed a buffered pattern; no peaks
      associated with spraying or with instantaneous variations of the flow rate or
      inlet emissions were observed. The model, which includes the prediction of the
      dissolved carbon in the water tank, has been proven as a very useful tool in
      identifying the governing processes of biotrickling filtration. 

PMID- 25594780
TI  - A method for screening climate change-sensitive infectious diseases.
AB  - Climate change is a significant and emerging threat to human health, especially
      where infectious diseases are involved. Because of the complex interactions
      between climate variables and infectious disease components (i.e., pathogen, host
      and transmission environment), systematically and quantitatively screening for
      infectious diseases that are sensitive to climate change is still a challenge. To
      address this challenge, we propose a new statistical indicator, Relative
      Sensitivity, to identify the difference between the sensitivity of the infectious
      disease to climate variables for two different climate statuses (i.e., historical
      climate and present climate) in non-exposure and exposure groups. The case study
      in Anhui Province, China has demonstrated the effectiveness of this Relative
      Sensitivity indicator. The application results indicate significant sensitivity
      of many epidemic infectious diseases to climate change in the form of changing
      climatic variables, such as temperature, precipitation and absolute humidity. As
      novel evidence, this research shows that absolute humidity has a critical
      influence on many observed infectious diseases in Anhui Province, including
      dysentery, hand, foot and mouth disease, hepatitis A, hemorrhagic fever, typhoid
      fever, malaria, meningitis, influenza and schistosomiasis. Moreover, some
      infectious diseases are more sensitive to climate change in rural areas than in
      urban areas. This insight provides guidance for future health inputs that
      consider spatial variability in response to climate change. 

PMID- 25594783
TI  - Health equity in humanitarian emergencies: a role for evidence aid.
AB  - Humanitarian emergencies require a range of planned and coordinated actions:
      security, healthcare, and, as this article highlights, health equity responses.
      Health equity is an evidence-based science that aims to address unfair and unjust
      health inequality outcomes. New approaches are using health equity to guide the
      development of community programs, equity methods are being used to identify
      disadvantaged groups that may face health inequities in a humanitarian emergency,
      and equity is being used to prevent unintended harms and consequences in
      interventions. Limitations to health equity approaches include acquiring
      sufficient data to make equity interpretations, integrating disadvantage
      populations in to the equity approach, and ensuring buy-in from decision-makers.
      This article uses examples from World Health Organization, Refugee Health
      Guidelines and Health Impact Assessment to demonstrate the emerging role for
      health equity in humanitarian emergencies. It is based on a presentation at the
      Evidence Aid Symposium, on 20 September 2014, at Hyderabad, India. 

PMID- 25594781
TI  - Neighborhood environment perceptions and the likelihood of smoking and alcohol
      use.
AB  - Neighborhood characteristics are important correlates for a variety of health
      outcomes. Among several health risk behaviors, smoking and alcohol use have
      significant consequences. Perceptions of neighborhood problems are associated
      with depressive symptoms, lower physical activity, and lower quality of life.
      However, it is unclear which perceived aspects of neighborhoods might be related
      to smoking and drinking. We examined whether perceived neighborhood
      characteristics were associated with smoking and drinking patterns using data
      from US metropolitan Midwestern area adults. Participants completed surveys
      including sociodemographic characteristics, neighborhood perceptions, behavioral
      and psychological health. For men, negative perceptions of neighborhood
      infrastructures were significant predictors for smoking and binge drinking. Among
      women, no perceived environmental factors were associated with smoking or
      drinking. However, education was a significant negative predictor for smoking. As
      age increased, the likelihood of using cigarettes, heavy and binge drinking in
      women decreased significantly. Depression was a positive predictor for smoking
      and heavy drinking in men and women, respectively. These findings indicate that
      the perceived neighborhood infrastructure was predictive of health behaviors
      among men, even after adjusting for key confounders. Closer attention may need to
      be paid to the role of neighborhood environmental characteristics along with
      individual-level characteristics in influencing unhealthy behaviors. 

PMID- 25594782
TI  - Short-term variability and predictors of urinary pentachlorophenol levels in Ohio
      preschool children.
AB  - Pentachlorophenol (PCP) is a persistent and ubiquitous environmental contaminant.
      No published data exist on the temporal variability or important predictors of
      urinary PCP concentrations in young children. In this further analysis of study
      data, we have examined the associations between selected sociodemographic or
      lifestyle factors and urinary PCP concentrations in 115 preschool children over a
      48-h period and assessed the 48-hour variability of urinary PCP levels in a
      subset of 15 children. Monitoring was performed at 115 homes and 16 daycares in
      Ohio (USA) in 2001. Questionnaires/diaries and spot urine samples were collected
      from each child. The median urinary PCP level was 0.8 ng/mL (range < 0.2-23.8
      ng/mL). The intraclass correlation coefficient for urinary PCP was 0.42, which
      indicates fairly low reliability for a single sample over a 48-h period. In a
      multiple regression model, age of home and ln(creatinine levels) were significant
      predictors and sampling season, time spent outside, and pet ownership were
      marginally significant predictors of ln(urinary PCP levels), collectively
      explaining 29% of the variability of PCP in urine. To adequately assess short
      term exposures of children to PCP, several spot urine measurements are likely
      needed as well as information regarding residence age, seasonality, time spent
      outdoors, and pet ownership. 

PMID- 25594784
TI  - A clean and general strategy to decorate a titanium metal-organic framework with
      noble-metal nanoparticles for versatile photocatalytic applications.
AB  - We demonstrate a facile and general approach for the fabrication of highly
      dispersed Au, Pd, and Pt nanoparticles (NPs) on MIL-125(Ti) without using extra
      reducing and capping agents. Noble-metal NP formation is directed by an in situ
      redox reaction between the reductive MIL-125(Ti) with Ti(3+) and oxidative metal
      salt precursors. The resulting composites function as efficient photocatalysts. 

PMID- 25594785
TI  - Attachment in romantic relationships and somatization.
AB  - Adult attachment representations have been considered to play a role in the
      development and treatment of somatizing behavior. In this study, the associations
      between the two attachment dimensions avoidance and anxiety and dimensions of
      psychopathology (somatization, depression, and general anxiety) were explored.
      The sample consists of 202 outpatients diagnosed with a somatoform disorder. Data
      were collected via self-report measures. A path analysis shows that the two
      attachment dimensions are not directly associated with somatization. There are,
      however, significant indirect associations between attachment and somatization
      mediated by depression and general anxiety, which are more pronounced for
      attachment anxiety than for attachment avoidance. The findings reveal that a low
      level of attachment security in romantic relationships, especially an anxious
      stance toward the partner, comes along with poor mental health, which in turn is
      related to a preoccupation with somatic complaints. Implications for the
      treatment of somatizing patients are discussed. 

PMID- 25594786
TI  - Intensive multidisciplinary treatment of severe somatoform disorder: a
      prospective evaluation.
AB  - Chronic severe somatoform disorder (SFD) is resistant to treatment. In a
      prospective observational study, we evaluated an intensive multidisciplinary
      treatment focusing on body-related mentalization and acceptance. Patients
      included in the study were 183 (146 women, 37 men) of 311 eligible patients with
      chronic severe SFD, referred consecutively to a specialized tertiary care center
      between 2002 and 2009. Primary outcome measures were somatic symptoms (SCL-90)
      and health-related quality of life (EuroQol 5-Dimensional [EQ-5D]). These
      measures were assessed four times before treatment (on intake, twice during an
      observation period, at start of treatment) and four times after treatment (during
      follow-up for 2 years). Multilevel analysis was used to separate effects of time
      (maturation) and treatment. Results revealed significant improvements in SCL-90
      somatic symptoms (d = 0.51), EQ-5D index (d = 0.27), and EQ visual analogue scale
      (d = 0.56). Significant reductions were also observed in SCL-90 anxiety,
      depression, and overall psychopathology as well as in medical consumption
      associated with psychiatric illness (Trimbos/iMTA Questionnaire for Costs
      Associated With Psychiatric Illness). Large interindividual differences were
      found in treatment outcome. The long-term improvement seen in many patients
      suggests that intensive multidisciplinary tertiary care treatment is a useful
      approach to chronic severe SFD. 

PMID- 25594787
TI  - Psychiatrists' and primary care physicians' beliefs about overtreatment of
      depression and anxiety.
AB  - Critics say that physicians overdiagnose and overtreat depression and anxiety. We
      surveyed 1504 primary care physicians (PCPs) and 512 psychiatrists, measuring
      beliefs about overtreatment of depression and anxiety and predictions of whether
      persons would benefit from taking medication, investing in relationships, and
      investing in spiritual life. A total of 63% of PCPs and 64% of psychiatrists
      responded. Most agreed that physicians too often treat normal sadness as a
      medical illness (67% of PCPs and 62% of psychiatrists) and too often treat normal
      worry and stress as a medical illness (59% of PCPs, 55% of psychiatrists).
      Physicians who agreed were less likely to believe that depressed or anxious
      people would benefit "a lot" from taking an antidepressant (36% vs. 58% of PCPs)
      or antianxiety medication (25% vs. 42% of PCPs, 42% vs. 57% of psychiatrists).
      Most PCPs and psychiatrists believe that physicians too often treat normal
      sadness and worry as a medical illness. 

PMID- 25594788
TI  - Nonverbal communication of patients with borderline personality disorder during
      clinical interviews: a double-blind placebo-controlled study using intranasal
      oxytocin.
AB  - Interpersonal dysfunction is central to borderline personality disorder (BPD).
      Recent research has focused on the role of oxytocin (OT) in BPD, with mixed
      results regarding the processing of social information. Fifteen BPD patients and
      15 controls participated in two clinical interviews, one under OT and one under
      placebo, which were randomly conducted 1 week apart in a double-blind fashion.
      Nonverbal behavior was evaluated using the Ethological Coding System for
      Interviews. Childhood trauma was examined using the Childhood Trauma
      Questionnaire. The patients with BPD showed less affiliative behavior than the
      controls. Notably, the controls, but not the patients, displayed more affiliation
      when OT was given at T1 compared with OT given at T2. OT was also associated with
      less flight behavior in both groups when given at T1 compared with placebo. OT
      responses were unrelated to the patients' history of childhood trauma. The
      present findings are informative with respect to patients' nonverbal prosocial
      behavior in clinical settings. 

PMID- 25594789
TI  - Defining and refining self-harm: a historical perspective on nonsuicidal self
      injury.
AB  - Nonsuicidal self-injury (NSSI) is a newly proposed diagnostic category in the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Some
      contemporary historiography dismisses NSSI as a fiction of modern psychiatry.
      Although the exact definition and psychological meaning attributed to self-harm
      has not been static over history, there is a clear thread that connects Western
      asylum psychiatrists' thinking about self-harm to the current stand-alone
      diagnostic category of NSSI. Nineteenth-century psychiatrists identified a
      clinically meaningful difference between self-harm with and without the intent to
      die, between self-injurers who were psychotic and those who were not, and between
      self-injurers who made a single, serious mutilation and those who repetitively
      self-injured without causing permanent bodily damage. These same distinctions are
      apparent in the definition of NSSI. Thus, NSSI is a formalization of long-held
      observations about a category of people who repetitively self-injure without
      suicidal intent. 

PMID- 25594790
TI  - What do psychiatric patients believe regarding where control over their illness
      lies? Validation of the multidimensional health locus of control scale in
      psychiatric outpatient care.
AB  - Patients' perceived control constructs are important factors moderating health
      related behaviors. We established the psychometric properties of the Spanish
      version of the Form C Multidimensional Health Locus of Control Scale (C-MHLC) and
      assessed the usefulness of these measures in the clinical setting. A cross
      sectional survey querying about patients' health locus of control (HLOC) beliefs
      was offered to 607 psychiatric outpatients, of whom 507 accepted. The C-MHLC
      scale and the General Perceived Self-Efficacy Scale were completed. The
      psychiatric patients believe that their psychiatrist plays a crucial role in
      improving their state of health. The men scored higher than the women in internal
      dimension; the women scored higher in other people external dimension. Age,
      treatment time, and number of psychoactive drugs used showed significant
      differences in HLOC dimensions. Self-efficacy correlated positively with internal
      dimension and negatively with external dimensions. The results showed the
      validity of the four-factor structure of the Spanish version of the C-MHLC. 

PMID- 25594791
TI  - Extended family and friendship support networks are both protective and risk
      factors for major depressive disorder and depressive symptoms among African
      Americans and black Caribbeans.
AB  - This study explores relationships between lifetime and 12-month Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) major depressive
      disorder (MDD), depressive symptoms, and involvement with family and friends
      within a national sample of African-American and Black Caribbean adults (n =
      5191). MDD was assessed using the DSM-IV World Mental Health Composite
      International Diagnostic Interview and depressive symptoms were assessed using
      the Center for Epidemiologic Studies-Depression subscale and the K6. Findings
      indicated that among both populations, close supportive ties with family members
      and friends are associated with lower rates of depression and MDD. For African
      Americans, closeness to family members was important for both 12-month and
      lifetime MDD, and both family and friend closeness were important for depressive
      symptoms. For Caribbean Blacks, family closeness had more limited associations
      with outcomes and was directly associated with psychological distress only.
      Negative interactions with family (conflict, criticisms), however, were
      associated with higher MDD and depressive symptoms among both African-Americans
      and Black Caribbeans. 

PMID- 25594793
TI  - Processing of facial and nonsocial information is differentially associated with
      severity of symptoms in patients with multiepisode schizophrenia.
AB  - Patients with schizophrenia show impairments in social cognitive abilities, such
      as recognizing facial emotions. However, the relation to symptoms remains
      unclear. The goal of this study was to explore whether facial emotion recognition
      and face identity recognition are associated with severity of symptoms and to
      which extent associations with symptoms differ for processing of social versus
      nonsocial information. Facial emotion recognition, face recognition, and abstract
      pattern recognition were evaluated in 98 patients with multiepisode
      schizophrenia. Severity of symptoms was measured using a five-factor model of the
      Positive and Negative Syndrome Scale. Results show that facial emotion
      recognition and, to a lesser extent, face recognition were predominantly
      associated with severity of disorganization symptoms. In contrast, recognition of
      nonsocial patterns was associated with negative symptoms, excitement, and
      emotional distress. Reaction time rather than accuracy of social cognition
      explained variance in symptomatology. These results lead to the conclusion that
      facial emotion processing in schizophrenia appears to be associated with severity
      of symptoms, especially disorganization. 

PMID- 25594792
TI  - A quantitative review of cognitive functioning in homeless adults.
AB  - Homeless people experience elevated rates of risk factors for cognitive
      impairment. We reviewed available peer-reviewed studies reporting data from
      objective measures of cognition in samples identified as homeless. Pooled sample
      weighted estimates of global cognitive screening measures, full-scale
      intelligence quotient (IQ), and premorbid IQ were calculated, in addition to
      pooled sample characteristics, to understand the representativeness of available
      studies. A total of 24 unique studies were identified, with 2969 subjects. The
      pooled estimate for the frequency of cognitive impairment was 25%, and the mean
      full-scale IQ score was 85, 1 standard deviation below the mean of the normal
      population. Cognitive impairment was found to be common among homeless adults and
      may be a transdiagnostic problem that impedes rehabilitative efforts in this
      population. Comparatively little data are available about cognition in homeless
      women and unsheltered persons. 

PMID- 25594794
TI  - Tandem Synthesis of 3-chloro-4-iodoisoxazoles from 1-copper(I) alkynes,
      dichloroformaldoxime, and molecular iodine.
AB  - A tandem synthesis for structurally novel 3-chloro-4-iodoisoxazoles was developed
      by simply mixing 1-copper(I) alkynes, dichloroformaldoxime, and molecular iodine
      together. The combination of 1-copper(I) alkyne and molecular iodine was well
      used as a synthetic equivalent of 1-iodoalkyne without the need for tedious
      preparation, purification, and storage of 1-iodoalkyne. 

PMID- 25594795
TI  - Interpretation of osmotic gradient ektacytometry (osmoscan) data: a comparative
      study for methodological standards.
AB  - Osmotic gradient ektacytometry (measuring elongation index in the function of
      osmolality at a constant shear stress) is a sensitive method to analyze red blood
      cell (RBC) deformability and investigating the optimal osmolality range for the
      cells in normal or pathophysiological cellular and micro-environmental
      conditions. However, the methodological conditions are different, since the
      results are influenced by the applied shear stress (SS). In this study we
      investigated rat, dog, pig and human blood samples at SS of 1, 2, 3, 5, 10, 20
      and 30 Pa. To describe the range being related to the cell deformability, we
      introduced new calculated parameters obtained from the raw data of the elongation
      index (EI)-osmolality (O) curves. Our results showed that: (1) Osmoscan data
      tested at 20 or 30 Pa do not differ significantly from each other; (2) Under SS
      of 20 Pa the EImax, the O (EImax), the EI min and the area under curve nearly
      linearly decrease in the function of SS with different slope in rat, dog, pig and
      human blood; (3) Measurements under 3 Pa SS become unstable; (4) The differences
      between minimal and maximal EI and the belonging osmolality values, and their
      ratios, as new calculated parameters (DeltaEI, DeltaO, DeltaEI/DeltaO,
      EImax/EImin and O (EImax)/Omin) can be suitable for further analysis of the
      osmoscan curves together with other hemorheological parameters describing RBC
      deformability; and (5) Decreased erythrocyte deformability (by rigidifying with
      glutaraldehyde) can be reflected well with the following, calculated osmoscan
      parameters: DeltaO, rO, rEI/rO and DeltaEI/DeltaO.

PMID- 25594796
TI  - The relationship between on-clopidogrel platelet reactivity, genotype, and post
      percutaneous coronary intervention outcomes in Chinese patients.
AB  - BACKGROUND: High on-clopidogrel platelet reactivity reflects a poor response to
      clopidogrel and is associated with ischemic events, which has been attributed to
      several factors such as demographic, clinical characteristics and a polymorphism
      of CYP2C19. Some new platelet assays monitoring on-clopidogrel platelet
      reactivity are currently available in China, but their relevance to the CYP2C19
      genotype and post-percutaneous coronary intervention outcomes remain to be
      elucidated. METHODS: Patients were prospectively included if they had a
      successful percutaneous coronary intervention (PCI) for acute coronary syndrome
      (ACS) and received clopidogrel and aspirin. CYP2C19 loss-of function genotype,
      adenosine diphosphate (ADP)-induced maximum platelet aggregation rate (MPA ADP)
      measured by light transmittance aggregometry, ADP-induced platelet-fibrin clot
      strength (MA ADP) measured by thrombelastography, platelet reactivity index (PRI)
      measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP), and the
      occurrence of 6-month major adverse cardiovascular events (MACE) were assessed in
      178 patients. RESULTS: High on-treatment platelet reactivity prevalence defined
      by MPA ADP > 46.0%, MA ADP > 47 mm and PRI > 50.0% was 27.0%, 24.2%, and 61.2%,
      respectively. ADP-specific assays (VASP PRI) differed according to CYP2C19
      genotype, with a significant gene-dose effect (PMs > IMs > EMs, p < 0.05).
      Multivariate analysis showed MPA ADP > 46.0% and MA ADP > 47 mm to be independent
      predictors of MACE at 6 months. CONCLUSIONS: CYP2C19 loss-of function genotypes
      with the *2 and/or *3 allele are highly prevalent in the Chinese population and
      are associated with higher residual platelet reactivity. High on-treatment
      platelet reactivity defined by MPA ADP or MA ADP predicts an increased risk of
      MACE for ACS patients undergoing PCI.

PMID- 25594797
TI  - Reproducibility of oscillometrically measured arterial stiffness indices: Results
      of the SAPALDIA 3 cohort study.
AB  - BACKGROUND: There is an increasing interest in oscillometric arterial stiffness
      measurement for cardiovascular risk stratification. We assessed reproducibility
      of the cuff-based arterial stiffness measures cardio-ankle vascular index (CAVI),
      brachial-ankle pulse wave velocity (baPWV) and peripheral augmentation index
      (pAI) in a subsample of the second follow-up of the Swiss Cohort Study on Air
      Pollution and Lung and Heart Diseases in Adults (SAPALDIA 3). METHODS: CAVI,
      baPWV and pAI were measured twice within 90 days in a representative subsample (n
      = 105) of SAPALDIA 3 with a mean age of 63 years (52.4% female). RESULTS: The
      mean coefficient of variation for CAVI was 4.4%, baPWV 3.9%, and pAI 7.4%. The
      intraclass correlation coefficient ranged from 0.6 for pAI to 0.8 for CAVI, and
      0.9 for baPWV. The mixed linear model revealed that 68.7%/80.1%/55.0% of the
      CAVI/baPWV/pAI variance was accounted for by the subject, 5.2%/8.1%/ < 0.01% by
      the fieldworker, 6.7%/7.8%/28.5% by variation between measurement days, and
      19.4%/4%/16.5% by measurement error. Bland-Altman plots showed no particular
      dispersion patterns except for pAI. CONCLUSIONS: Oscillometric arterial stiffness
      measurement by CAVI and baPWV has proved to be highly reproducible in Caucasians.
      Results of the pAI showed lower reproducibility. CAVI and baPWV can be
      implemented as easy-to-apply arterial stiffness measures in population wide
      cardiovascular risk assessment in Caucasians.

PMID- 25594798
TI  - Lower hemoglobin with lower ferritin - results from the HUNT 2 Study.
AB  - AIM: We wanted to study the association between blood hemoglobin concentration (b
      hemoglobin) and serum ferritin concentration (s-ferritin) in a healthy female
      population, and compare the findings to those in a previous study of ambulant
      female patients. METHODS: We compared median b-hemoglobin and the fraction with
      anemia in groups of women with s-ferritin from less than 10 MUg/L to 100 MUg/L.
      These women, aged 20-55 years, were part of a health screening survey (HUNT 2)
      where they reported to have 'good' or 'very good' general health and were found
      to have normal s-creatinine. The s-ferritin values were adjusted to the level of
      the previous study. The 10, 50 and 90 percentiles of b-hemoglobin were modelled
      as functions of s-ferritin using quantile regression. RESULTS: Among 2122 healthy
      females the entire b-hemoglobin distribution was shifted downwards in women with
      s-ferritin less than 20 MUg/L. Accordingly, the median b-hemoglobin was
      statistically significantly lower. In women with s-ferritin less than 20 MUg/L
      the fraction with anemia was 0.15. CONCLUSIONS: Lower s-ferritin is associated
      with lower b-hemoglobin in many more subjects than those labelled anemic.

PMID- 25594799
TI  - Lysosomal enzymes in serum and synovial fluid in patients with osteoarthritis.
AB  - OBJECTIVE: To assess the activity of arylsulfatase (AS), acid phosphatase (ACP),
      cathepsin D (CAT-D) and alpha-1 antitrypsin (AAT) in blood serum and synovial
      fluid (SF) of patients with hip or knee osteoarthritis (OA). METHODS: The study
      included 43 subjects with OA (35 hip OA, 8 knee OA), submitted total joint
      replacement. The control group consisted of 58 subjects with no past history of
      musculoskeletal disorders. RESULTS: The OA blood serum samples showed a
      significantly higher level of lysosomal enzymes activity than in the control
      group (AS by 17.8%, AAT by 42.4%); only the CAT-D activity decreased by 50%). AS,
      ACP and CAT-D activities were about two-fold higher in SF when compared with
      blood of OA patients. The differences between the genders were visible in the SF:
      Total protein concentration, activity of ACP (both higher in OA men) and activity
      of CAT-D (higher in OA women). Between the involved hip and knee, there were no
      significant differences in all estimated parameters in the blood serum of the OA
      group. In regard to the SF, only ACP activity was significantly higher in
      patients with a hip involved. CONCLUSIONS: The osteoarthritic SF enzymatic
      profile differs from that in normal joints. The OA in joints is not reflected in
      the systemic response. Our preliminary results suggest further studies on role of
      lysosomal enzymes (ACP and AS) as biomarkers for the detection of osteoarthritis.

PMID- 25594800
TI  - Adair-based hemoglobin equilibrium with oxygen, carbon dioxide and hydrogen ion
      activity.
AB  - As has been known for over a century, oxygen binding onto hemoglobin is
      influenced by the activity of hydrogen ions (H+), as well as the concentration of
      carbon dioxide (CO2). As is also known, the binding of both CO2and H+ on terminal
      valine-1 residues is competitive. One-parametric situations of these hemoglobin
      equilibria at specific levels of H+, O2or CO2are also well described. However, we
      think interpolating or extrapolating this knowledge into an 'empirical' function
      of three independent variables has not yet been completely satisfactory. We
      present a model that integrates three orthogonal views of hemoglobin oxygenation,
      titration, and carbamination at different temperatures. The model is based only
      on chemical principles, Adair's oxygenation steps and Van't Hoff equation of
      temperature dependences. Our model fits the measurements of the Haldane
      coefficient and CO2hemoglobin saturation. It also fits the oxygen dissociation
      curve influenced by simultaneous changes in H+, CO2and O2, which makes it a
      strong candidate for integration into more complex models of blood acid-base with
      gas transport, where any combination of mentioned substances can appear.

PMID- 25594803
TI  - Highly active magnetic bismuth tungstate/magnetite composite under visible light
      irradiation in the presence of hydrogen peroxide.
AB  - Bi2WO6/Fe3O4 composites were synthesized using hydrothermal method and their
      photocatalytic activity to degrade rhodamine B (RhB) under visible light
      irradiation assisted with H2O2 and underlying mechanisms were investigated. The
      composites were 3D flower-like microspheres constructed by 2D Bi2WO6 nanosheets
      loaded with spherical Fe3O4 nanoparticles. The composited photocatalysts could be
      easily harvested from the reaction solution by an external magnetic field. In the
      presence of H2O2, a large amount of hydroxyl radicals (.OHs) were produced by
      H2O2 reacting with photogenerated electrons. Fe3O4 not only promoted the
      separation of hole-electron pairs but also acted as a Fenton-like reagent,
      expediting the production of .OH. Thus, the composites in the presence of H2O2
      displayed much higher photocatalytic efficiency to degrade RhB than pure Bi2WO6.
      98% of RhB (initial concentration 10 mg/L) was degraded in 2 h visible
      irradiation and 60% of total organic carbon (TOC) was removed in 3 h by 0.5 g/L
      Bi2WO6/Fe3O4 (5:1). The composite displayed high photodegradation efficiency at
      pH 3-9. Our study suggests that a visible light driven and highly active magnetic
      photocatalyst-Fenton coupling oxidation system may have potential application in
      water treatment and environmental cleaning.

PMID- 25594801
TI  - Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea
      predominant irritable bowel syndrome.
AB  - BACKGROUND: About one-third of patients with IBS-diarrhoea (irritable bowel
      syndrome-D) have evidence of increased bile acid synthesis or excretion. AIMS: To
      assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of
      BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual
      or random stool samples accurately reflect 48-h total faecal bile acid excretion
      and proportions of the main bile acids excreted and to study the faecal fat
      excretion in response to colesevelam. METHODS: A single-centre, unblinded, single
      dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)]
      orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and
      fasting serum C4 (7alpha-hydroxy-4-cholesten-3-one; surrogate of hepatic bile
      acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8
      days during colesevelam treatment. Stool 48-h samples and fasting serum were
      collected for faecal fat, faecal bile acid and serum C4. RESULTS: Colesevelam was
      associated with significantly increased faecal total bile acid excretion and
      deoxycholic acid excretion, increased serum C4 and more solid stool consistency.
      There was a significant inverse correlation between number of bowel movements per
      week and the total bile acid sequestered into stool during the last 48 h of
      treatment. Random stool samples did not accurately reflect 48-h total or
      individual faecal bile acid excretion. Sequestration of bile acids by colesevelam
      did not increase faecal fat. CONCLUSIONS: Colesevelam increases delivery of bile
      acids to stool while improving stool consistency, and increases hepatic bile acid
      synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are
      consistent with luminal bile acid sequestration by colesevelam.

PMID- 25594802
TI  - New insights on the structure of the picloram-montmorillonite surface complexes.
AB  - HYPOTHESIS: The environmental mobility and bioavailability of Picloram (PCM) are
      determined by the amine and carboxylate chemical groups interaction with the
      soils mineral phases. Clay particles, such as montmorillonite (Mt), and the pH
      value of the media could play an important role in adsorption processes. Thus,
      the study of the role of soil components other than organic matter deserves
      further investigation for a more accurate assessment of the risk of groundwater
      contamination. EXPERIMENTS: Samples with PCM adsorbed on Mt dispersions were
      prepared at pH 3-9. Subsequently, the dispersions were separated, washed,
      centrifuged and stored at room temperature. Picloram (PCM) herbicide interaction
      with surface groups of montmorillonite (Mt) was studied using XRD, DTA, FTIR and
      XPS techniques. FINDINGS: The entrance of PCM into the Mt basal space, in two
      different arrangements, perpendicular and planar, is proposed and the final
      arrangement depends on PCM concentration. The interaction of PCM with Mt surface
      sites through the nitrogen of the pyridine ring and carboxylic group of PCM,
      forming bidentate and bridge inner-sphere complexes was confirmed by FTIR and XPS
      analysis. The acidity constant of the PCM adsorbed on the Mt surface was
      calculated.

PMID- 25594804
TI  - Temperature dependence of aging kinetics of hectorite clay suspensions.
AB  - The aging of salt-free hectorite suspensions with different concentrations
      (c(L)=2.9, 3.2 and 3.5 wt%) stored for 2 days or 4 days was studied by rheology
      at different temperatures. The evolution of storage and loss moduli G' and G"
      during aging followed aging time-temperature superposition. The temperature
      dependence of the shift factor a(T), which reflected the aging kinetics, was
      interpreted by the reaction-limited colloidal aggregation (RLCA) mechanism with
      counterion condensation in calculating the double-layer interaction of the
      charged clay particles. Temperature dependence of the plateau modulus and yield
      stress of the suspension aged for 800 s was modeled with the soft glassy rheology
      (SGR) theory. The estimated noise temperature x indicated that the sample aged at
      higher temperature corresponded to a deeper quench in the nonergodic state. Under
      larger amplitude of oscillatory shear, the suspension exhibited a strain rate
      frequency superposition (SRFS). The shearing eliminated the effects of aging and
      heating.

PMID- 25594806
TI  - Properties and photochemistry of valence-induced-Ti(3+) enriched (Nb,N)-codoped
      anatase TiO2 semiconductors.
AB  - Nb and N codoped TiO2s are outstandingly versatile semiconductor oxides. Their
      high conductivity makes them valid alternatives to commercially available, but
      very expensive, conductive oxides. They show increased photonic efficiencies
      compared to the cases of solely Nb or N doped TiO2, when used as visible light
      sensitised photocatalysts. Furthermore, they are excellent materials for O2
      sensors at very low temperature. Despite these remarkable properties, a clear
      picture of the electronic and optical mechanisms induced by the simultaneous
      presence of the dopants has just begun to be understood. Using a combination of
      electron paramagnetic resonance (EPR) spectroscopy, electrochemical impedance
      spectroscopy (EIS) and optical spectroscopy, we present here novel fundamental
      insights into the mechanisms responsible for the enhanced conductivity and
      visible light photochemistry. 

PMID- 25594805
TI  - Immunization with recombinant SFTSV/NSs protein does not promote virus clearance
      in SFTSV-infected C57BL/6J mice.
AB  - The severe fever with thrombocytopenia syndrome (SFTS), caused by a novel
      Phlebovirus in the Bunyaviridae family named SFTS virus (SFTSV), is an emerging
      hemorrhagic fever with a wide distribution and high case-fatality rate. Neither
      effective treatment nor vaccines are available to treat and prevent this disease
      to date. It was recently reported that SFTSV nonstructural protein in S segment
      (SFTSV/NSs) functioned as the interferon (IFN) antagonist targeting for
      suppressing host's innate immunity. This study was designed to investigate the
      potential of recombinant SFTSV (rSFTSV)/NSs protein for inducing anti-NSs
      antibodies by pre-exposure vaccination to block SFTSV/NSs in the SFTSV-infected
      C57BL/6J mice. All mice in the rSFTSV/NSs-vaccinated group, negative control
      group, and blank control group survived with no visible clinical abnormities
      throughout the experiment, except for their sacrifice for sampling at each
      observation point. However, unexpectedly, a negative effect on the bodyweight of
      rSFTSV/NSs-vaccinated mice was observed after 21 days postinoculation. Pre
      exposure vaccination with rSFTSV/NSs did not accelerate virus removal in mice
      though high titer of anti-NSs antibodies and elevated IFN-gamma were detected in
      sera. Before virus challenge, the rSFTSV/NSs-vaccinated mice and negative control
      mice had a larger amount of platelets (PLT) than the blank control mice, which
      indicated that Freund's adjuvants could stimulate PLT production. In the aspect
      of cytokines, the rSFTSV/NSs-vaccinated mice had a 5- to 10-fold increase in
      interleukin (IL)-2, IL-5, IL-6, IFN-gamma, and tumor necrosis factor-alpha, which
      probably just had a negative effect on the bodyweight of mice. In general,
      therefore, previous vaccination with rSFTSV/NSs did not accelerate virus
      clearance in the SFTSV-infected mice. 

PMID- 25594809
TI  - Step Up and Be Counted! Development of a national school health database.

PMID- 25594807
TI  - Anionic Lipid, pH-Sensitive Liposome-Gold Nanoparticle Hybrids for Gene Delivery 
      Quantitative Research of the Mechanism.
AB  - Gene therapy is a potential method for treating a large range of diseases. Gene
      vectors are widely used in gene therapy for promoting the gene delivery
      efficiency to the target cells. Here, gold nanoparticles (AuNPs) coated with
      dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine
      (DOPE) are synthesized using a facile method for a new gene vector (DODAB/DOPE
      AuNPs), which possess 3- and 1.5-fold higher transfection efficiency than those
      of DODAB-AuNPs and a commercial transfection agent, respectively. Meanwhile, it
      is nontoxic with concentrations required for effective gene delivery. Imaging and
      quantification studies of cellular uptake reveal that DOPE increases gene copies
      in cells, which may be attributed to the smaller size of AuNPs/DNA complexes. The
      dissociation efficiency of DNA from the endocytic pathway is quantified by
      incubating with different buffers and investigated directly in the cells. The
      results suggest that DOPE increases the internalization of AuNPs/DNA complexes
      and promotes DNA release from early endosomes for the vector is sensitive to the
      anionic lipid membrane and the decreasing pH along the endocytic pathway. The new
      vector contains the potential to be the new alternative as gene delivery vector
      for biomedical applications. 

PMID- 25594811
TI  - Uranium in drinking-water: a unique case of guideline value increases and
      discrepancies between chemical and radiochemical guidelines.
AB  - BACKGROUND: Uranium represents a unique case for an element naturally present in
      the environment, as its chemical guideline value in drinking water significantly
      increased from 2 MUg/L in 1998 up to 15 MUg/L in 2004 and then to 30 MUg/L in
      2011, to date corresponding to a multiplication factor of 15 within a period of
      just 13 years. OBJECTIVES: In this commentary we summarize the evolution of
      uranium guideline values in drinking-water based on both radiological and
      chemical aspects, emphasizing the benefit of human studies and their contribution
      to recent recommendations. We also propose a simpler and better consistency
      between radiological and chemical values. DISCUSSION: The current chemical
      guideline value of 30 MUg/L is still designated as provisional because of
      scientific uncertainties regarding uranium toxicity. During the same period, the
      radiological guideline for (238)U increased from 4 Bq/L to 10 Bq/L while that for
      (234)U decreased from 4 Bq/L to 1 Bq/L. These discrepancies are discussed here,
      and a value of 1 Bq/L for all uranium isotopes is proposed to be more consistent
      with the current chemical value of 30 MUg/L. CONCLUSION: Continuous progress in
      the domains of toxicology and speciation should enable a better interpretation of
      the biological effects of uranium in correlation with epidemiological human
      studies. This will certainly aid future proposals for uranium guideline values.

PMID- 25594808
TI  - Sleep in the intensive care unit.
AB  - Sleep is an important physiologic process, and lack of sleep is associated with a
      host of adverse outcomes. Basic and clinical research has documented the
      important role circadian rhythm plays in biologic function. Critical illness is a
      time of extreme vulnerability for patients, and the important role sleep may play
      in recovery for intensive care unit (ICU) patients is just beginning to be
      explored. This concise clinical review focuses on the current state of research
      examining sleep in critical illness. We discuss sleep and circadian rhythm
      abnormalities that occur in ICU patients and the challenges to measuring
      alterations in circadian rhythm in critical illness and review methods to measure
      sleep in the ICU, including polysomnography, actigraphy, and questionnaires. We
      discuss data on the impact of potentially modifiable disruptors to patient sleep,
      such as noise, light, and patient care activities, and report on potential
      methods to improve sleep in the setting of critical illness. Finally, we review
      the latest literature on sleep disturbances that persist or develop after
      critical illness.

PMID- 25594812
TI  - High-resolution, high-aspect ratio conductive wires embedded in plastic
      substrates.
AB  - A novel method is presented to fabricate high-resolution, high-aspect ratio metal
      wires embedded in a plastic substrate for flexible electronics applications. In a
      sequential process, high-resolution channels connected to low-resolution
      reservoirs are first created in a thermosetting polymer by imprint lithography. A
      reactive Ag ink is then inkjet-printed into the reservoirs and wicked into the
      channels by capillary forces. These features serve as a seed layer for copper
      deposition inside the channels via electroless plating. Highly conductive wires
      (>50% bulk metal) with minimum line width and spacing of 2 and 4 MUm,
      respectively, and an aspect ratio of 0.6 are obtained. The embedded wires exhibit
      good mechanical flexibility, with minimal degradation in electrical performance
      after thousands of bending cycles. 

PMID- 25594813
TI  - Impact of navigable ultrasound: how much credit should we give to the "navigable"
      component?

PMID- 25594814
TI  - Response to: Can recurrence of chronic subdural hematoma be predicted?

PMID- 25594815
TI  - Comparing Angiographic Devascularization with Histologic Penetration after
      Preoperative Tumor Embolization with Onyx: What Indicates an Effective Procedure?
AB  - BACKGROUND AND PURPOSE: To assess Onyx (Covidien, Irvine, California, United
      States) efficacy as a preoperative embolic agent for neoplasms of the head, neck,
      and spine, and to compare angiographic and histologic evidence of tumor
      penetration as predictors of intraoperative blood loss. MATERIALS AND METHODS:
      Retrospective analysis of preoperative Onyx embolization procedures for treatment
      of head, neck, and spine tumors from 2009 to 2011. Patient demographics and
      information relating to the embolization procedure and operation were recorded.
      Measures of Onyx efficacy included intraoperative blood loss and length of
      surgery. Angiographic and histologic penetration, in addition to percentage of
      tumor devascularization, were assessed as predictors of efficacy. RESULTS: A
      total of 22 patients with 17 head or neck and 5 spinal lesions underwent trans
      arterial preoperative Onyx embolization. Good angiographic penetration was
      reported in 41% of tumors and central histologic penetration in 59%, with mean
      tumor devascularization of 85.3% (standard deviation [SD]: 12.6%). There was no
      relationship between angiographic and histologic Onyx penetrance. Mean surgical
      blood loss was 1342 mL (SD: 1327 mL), and length of surgery was 289 minutes (SD:
      162 minutes). Neither angiographic, nor histologic Onyx penetration predicted
      intraoperative blood loss (p = 0.38 and p = 0.32, respectively) or surgical
      length (p = 0.62 and 0.90, respectively). Devascularization was not associated
      with blood loss (p = 0.62), but it was a negative predictor of surgical length (p
      = 0.013). CONCLUSIONS: Preoperative Onyx embolization of head, neck, and spine
      tumors is capable of deep histologic tumor penetration, even when not visualized
      on angiography. The lack of association between measures of procedural adequacy
      suggests that using angiographic devascularization as a measure of procedural
      efficacy may be of limited utility.

PMID- 25594816
TI  - Transcranial electric stimulation for intraoperative motor evoked potential
      monitoring: dependence of required stimulation current on interstimulus interval
      value.
AB  - STUDY OBJECTIVE: To evaluate the relationship between stimulus intensity by
      constant current transcranial electric stimulation and interstimulus interval
      (ISI) for eliciting muscle motor evoked potentials (MEPs) in three different hand
      muscles and the tibialis anterior muscles. PATIENTS/MATERIAL AND METHODS: We
      tested intraoperatively different monophasic constant current pulses and ISIs in
      22 patients with clinically normal motor function. Motor thresholds of
      contralateral muscle MEPs were determined at 0.5 milliseconds (ms) pulse duration
      and ISIs of 1, 2, 3, 4, 5, and 10 ms using a train of 2, 3, and 5 monophasic
      constant current pulses of 62 to 104 mA before craniotomy and after closure of
      the dura mater. RESULTS: The lowest stimulation threshold to elicit MEPs in the
      examined muscles was achieved with a train of 5 pulses (ISI: 3 ms) before
      craniotomy, which was statistically significant compared with 2 pulses (ISI: 3
      ms) as well as 3 pulses (ISIs: 3 and 10 ms). An ISI of 3 ms gave the lowest motor
      thresholds with statistical significance compared with the ISIs of 4 ms (2
      pulses) and of 1 ms (3 pulses). All current intensity (mA) and ISI (ms)
      relationship graphs had a trend of the exponential function as y = a + bx + c rho
      (x), where y is intensity (mA) and x is ISI (ms). The minimum of the function was
      determined for each patient and each muscle. The difference was statistically
      significant between 3 and 5 pulses before craniotomy and between 3 and 5 pulses
      and 2 and 5 pulses after closure of the dura mater. CONCLUSION: In adult
      neurosurgical patients with a normal motor status, a train of 5 pulses and an ISI
      of 3 ms provide the lowest motor thresholds. We provided evidence of the
      dependence of required stimulation current on ISI.

PMID- 25594817
TI  - Pulsed Laser-induced Liquid Jet System for Treatment of Sellar and Parasellar
      Tumors: Safety Evaluation.
AB  - OBJECTIVE: The pulsed laser-induced liquid jet (LILJ) system is an emerging
      surgical instrument intended to assist both maximal removal of the lesion and
      functional maintenance through preservation of fine vessels and minimal damage to
      the surrounding tissue. The system ejects the minimum required amount of pulsed
      water through a handy bayonet-shaped catheter. We have already shown a
      significant increase in removal rate, in addition to a noteworthy reduction of
      intraoperative blood loss and procedure time in the treatment of large pituitary
      and skull base tumors in a single-institution series. The present study evaluated
      the safety of the system in multiple institutions. METHODS: The study included 46
      patients, 29 men and 17 women (mean age: 59.1 years) who underwent
      microsurgical/endoscopic resection of lesions in or in the vicinity of the
      pituitary fossa through the transsphenoidal approach between October 2011 and
      June 2012 at six institutions. The histologic diagnoses were pituitary adenoma
      (31 cases), meningioma (4), craniopharyngioma (3), cavernous angioma (2), and
      Rathke cyst cleft (1). Lesion volume ranged from 2.0 to 30.4 cm3 (mean: 3.7 cm3).
      Cavernous sinus invasion was observed in 11 cases and suprasellar extension in 29
      cases. RESULTS: Preservation of intralesional arteries (diameter: 150 um) was
      achieved in all situations in > 80% of cases. Intended surgical steps were
      achieved except for some restrictions in motion due to the use of an optical
      quartz fiber. No complications occurred directly related to the use of the
      device. CONCLUSIONS: The LILJ system can be used for safe removal of lesions in
      or in the vicinity of the pituitary fossa.

PMID- 25594818
TI  - Prealbumin as a serum biomarker of impaired perioperative nutritional status and
      risk for surgical site infection after spine surgery.
AB  - INTRODUCTION: Impaired perioperative nutritional status has been shown to be an
      important predictor of surgical morbidity and is the earliest marker of
      nutritional deficiency. No study, however, has examined serum prealbumin as a
      surrogate marker of nutritional status in patients undergoing spine surgery.
      METHODS: We performed a retrospective review of all patients who developed a
      postoperative deep wound infection after undergoing spine surgery at the
      University of Pittsburgh Medical Center from January 2008 through December 2011.
      Demographics, preoperative diagnosis, type of surgery, perioperative serum
      prealbumin level, time to infection, number and type of debridement procedures,
      and length of hospital stay were recorded. RESULTS: A total of 83 patients had
      prealbumin levels available at the time of presentation of infection. Mean
      patient age was 56 years, and 71% were women. Surgical treatment for the
      infection required between 1 and 13 debridements, and 21 (25%) of the 83 patients
      who had instrumentation placed at the time of the initial surgery required
      removal of their instrumentation. Inpatient hospitalizations were extended by an
      average of 13 days. Prealbumin levels were below normal in 82 (99%) of the 83
      patients; levels were < 7 mg/dL in 24 patients, between 7 and 11 mg/dL in 32
      patients, and between 11 and 19 mg/dL in 26 patients. CONCLUSIONS: All patients
      except one who developed postoperative deep wound infection after spine surgery
      had serum prealbumin levels in the malnutrition range at the time of
      presentation. The current study suggests serum prealbumin levels may be an
      inexpensive screening biomarker for nutritional status and risk stratification
      for postoperative infection after spine surgery.

PMID- 25594819
TI  - Microsurgical and Endoscopic Posterior Transcortical Keyhole Approach to the
      Atrium of the Lateral Ventricle: A Cadaveric Study.
AB  - OBJECTIVE: Accessing large lesions located in the atrium of the lateral ventricle
      without causing a neurologic deficit can be challenging. The aim of this study
      was to evaluate a modification of the posterior transcortical approach that may
      create sufficient exposure to the atrium of the lateral ventricle with less
      injury to the brain cortex and fibers using a technique that combines a
      microscope with an endoscope. MATERIAL AND METHODS: Craniotomy procedures
      performed using the posterior transcortical keyhole approach were simulated on 10
      adult cadaveric heads (20 hemispheres). The anatomical structures in the lateral
      ventricle were observed through the microscope and endoscope. Three distance
      measurements on the intraparietal sulcus were recorded. RESULTS: The anatomical
      structures related to the atrium of the lateral ventricle, including the calcar
      avis, corpus callosum bulb, caudate nucleus, pulvinar, and glomus, were clearly
      observed under the microscope. Via the endoscope, a wider visualization of
      anatomical structures could be obtained. The distance from the intersection of
      the intraparietal sulcus and postcentral sulcus to the cerebral longitudinal
      fissure was 35.36 +/- 1.06 mm, the depth of the intraparietal sulcus was 19.16 +/
      1.03 mm, and the distance from the bottom of the intraparietal sulcus to the
      lateral ventricle was 21.31 +/- 1.32 mm. CONCLUSIONS: The microsurgical posterior
      transcortical keyhole approach could provide an ideal exposure to the atrium and
      the posterior part of the body of the lateral ventricle. The endoscopic posterior
      transcortical keyhole approach demonstrated a wider viewing range compared with
      the microscope. An endoscopic-controlled or -assisted surgery may reduce damage
      to normal brain tissue, facilitate total resection of the lesion, and improve the
      surgical outcome.

PMID- 25594820
TI  - The Nelaton Catheter Guard for Safe and Effective Placement of Subdural Drain for
      Two-Burr-Hole Trephination in Chronic Subdural Hematoma: A Technical Note.
AB  - BACKGROUND: For chronic subdural hematoma, placement of a Blake drain with a two
      burr-hole craniotomy is often preferred. However, the placement of such drains
      carries the risk of penetrating the brain surface or damaging superficial venous
      structures. OBJECTIVE: To describe the use of a Nelaton catheter for the
      placement of a subdural drain in two-burr-hole trephination for chronic subdural
      hematoma. METHOD: A Nelaton catheter was used to guide placement of a Blake drain
      into the subdural hematoma cavity and provide irrigation of the hematoma cavity.
      With the two-burr-hole method, the Nelaton catheter could be removed easily via
      the frontal burr hole after the Blake drain was in place. RESULTS: We used the
      Nelaton catheters in many surgical procedures and found it a safe and easy
      technique. This method allows the surgeon to safely direct the catheter into the
      correct position in the subdural space. CONCLUSIONS: This tool has two
      advantages. First, the use of a small and flexible Nelaton catheter is a safe
      method for irrigation of a chronic subdural hematoma cavity. Second, in
      comparison with insertion of subdural drainage alone through a burr hole, the
      placement of the Nelaton catheter in subdural space is easier and the risk of
      damaging relevant structures such as cortical tissue or bridging veins is lower.
      Thus this technique may help to avoid complications when placing a subdural
      drain.

PMID- 25594821
TI  - MRI-based radiation-free method for navigated percutaneous radiofrequency
      trigeminal rhizotomy.
AB  - BACKGROUND/STUDY AIMS: Percutaneous radiofrequency trigeminal rhizotomy (RTR) is
      a standardized treatment for trigeminal neuralgia, yet it has been associated
      with serious complications related to the cannulation of the foramen ovale. Some
      of these complications, such as carotid injury, are potentially lethal.
      Neuronavigation was recently proposed as a method to increase the procedure's
      safety. All of the techniques described so far rely on pre- or intraoperative
      computed tomography scanning. Here we present a simple method based on magnetic
      resonance imaging (MRI) (radiation free) used to target the foramen ovale under
      navigation guidance. PATIENTS/MATERIAL AND METHODS: We retrospectively analyzed
      nine patients who had undergone navigated percutaneous RTR based solely on
      preoperative MRI and compared them with 35 patients who underwent conventional
      RTR guided by fluoroscopy. We analyzed immediate and late outcome and categorized
      the results into pain free, > 70% pain reduction, and persistent pain. We also
      compared groups in terms of the duration of the procedure and the complication
      rates. Here we describe the navigation method in detail and review the anatomical
      landmarks for target definition. RESULTS: The duration of the surgical procedure
      was similar in both groups (32.1 in the standard technique versus 34.5 minutes
      with navigation; p = 0.5157). There was no significant difference between groups
      regarding pain reduction at the immediate (p = 1.0) or late follow-up (p =
      0.6284) time points. Furthermore, no serious complications were observed in the
      navigated group. CONCLUSIONS: We present a simple radiation-free method for
      neuronavigation-assisted percutaneous RTR. This method proved to be safe and
      effective, and it is especially recommended for young, inexperienced
      neurosurgeons.

PMID- 25594822
TI  - Insulin action in the human brain: evidence from neuroimaging studies.
AB  - Thus far, little is known about the action of insulin in the human brain.
      Nonetheless, recent advances in modern neuroimaging techniques, such as
      functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG),
      have made it possible to investigate the action of insulin in the brain in
      humans, providing new insights into the pathogenesis of brain insulin resistance
      and obesity. Using MEG, the clinical relevance of the action of insulin in the
      brain was first identified, linking cerebral insulin resistance with peripheral
      insulin resistance, genetic predisposition and weight loss success in obese
      adults. Although MEG is a suitable tool for measuring brain activity mainly in
      cortical areas, fMRI provides high spatial resolution for cortical as well as
      subcortical regions. Thus, the action of insulin can be detected within all
      eating behaviour relevant regions, which include regions deeply located within
      the brain, such as the hypothalamus, midbrain and brainstem, as well as regions
      within the striatum. In this review, we outline recent advances in the field of
      neuroimaging aiming to investigate the action of insulin in the human brain using
      different routes of insulin administration. fMRI studies have shown a significant
      insulin-induced attenuation predominantly in the occipital and prefrontal
      cortical regions and the hypothalamus, successfully localising insulin-sensitive
      brain regions in healthy, mostly normal-weight individuals. However, further
      studies are needed to localise brain areas affected by insulin resistance in
      obese individuals, which is an important prerequisite for selectively targeting
      brain insulin resistance in obesity. 

PMID- 25594823
TI  - Facile synthesis of water-soluble Zn-doped AgIn5S8/ZnS core/shell fluorescent
      nanocrystals and their biological application.
AB  - Here we demonstrate a novel and facile strategy of highly luminescent water
      soluble Zn-doped AgIn5S8 (ZAIS) nanocrystals and ZAIS/ZnS core/shell structures,
      which were based on hydrothermal reaction between the acetate salts of the
      corresponding metals and sulfide precursor in the presence of l-cysteine at 110 
      degrees C in a Teflon-lined autoclave. The photoluminescent (PL) emission
      wavelength can be conveniently tuned from 560 to 650 nm by tailoring the
      stoichiometric ratio of [Ag]/[Zn]. The as prepared nanocrystals were
      characterized systematically and exhibit long PL lifetimes more than 100 ns. The
      influence of experimental conditions, including concentration of l-cysteine and
      reaction temperature, was investigated. In addition, we performed a coating
      procedure with the ZnS shell outside the ZAIS core and showed excellent PL
      quantum yields up to 35%. The in vitro experiment exhibited quite low
      cytotoxicity and marvelous biocompatibility, revealing their promising prospect
      in bioscience. Furthermore, the obtained ZAIS/ZnS nanocompounds (NCs) were
      covalently conjugated to alpha-fetoprotein antibodies and targeted fluorescent
      imaging for hepatocellular carcinoma cells was realized. 

PMID- 25594824
TI  - Immediate recall of health issues discussed during a pre-travel consultation.
AB  - BACKGROUND: An important role of pre-travel consultations is to improve
      travelers' understanding of travel-related diseases, but the efficacy of
      education provided is unknown. This study sought to assess recall and knowledge
      immediately following a pre-travel consultation. METHODS: The study was conducted
      at a hospital-based pre-travel clinic in Melbourne, Australia. Travelers aged
      >=16 years seen between September 2010 and March 2012 were invited to complete an
      anonymous self-administered questionnaire immediately following their
      consultation to assess knowledge of appropriate preventive measures and
      presumptive self-treatment strategies for common travel risks. The doctor of each
      participating traveler also completed a survey regarding issues discussed.
      RESULTS: A total of 300 participants were recruited (34% male, median age 31
      years). Most were traveling for vacation (77%) and reported previous travel
      (95%). Main travel destinations were Asia (43%), Americas (21%), and Africa
      (17%). Doctors' and travelers' surveys showed variable levels of concordance: 94%
      of patients recalled discussion of malaria, 84% rabies, and 76% dengue. For
      malaria, 95% remembered discussions regarding insect repellents, and 92% recalled
      that medical advice should be sought if fever developed. For travelers with whom
      rabies was discussed, 94% recalled that medical advice must be urgently sought
      following a bite/scratch. For travelers' diarrhea (TD), 99% knew to drink only
      boiled/bottled water, but 13% did not recall avoiding unpeeled fruit/vegetables
      as a prevention strategy. There was 20% discordance between doctors and travelers
      regarding antibiotics for TD self-treatment, but only 4% discordance regarding
      prescription of malaria prophylaxis. Factors associated with improved recall were
      doctor discussion, previous travel, and a university education. CONCLUSIONS: Key
      travel health messages are well assimilated after pre-travel consultation.
      However, large amounts of information are discussed and immediate recollection of
      all information is not possible. This study reinforces the importance of
      providing supplementary information (eg, written and/or electronic resources) to
      accompany pre-travel consultations.

PMID- 25594825
TI  - Phosphorus removal using a microalgal biofilm in a new biofilm photobioreactor
      for tertiary wastewater treatment.
AB  - Eutrophication of surface water has been an important environmental issue for
      nearly half a century. High concentrations of phosphorus contribute to the
      process of eutrophication, resulting in the demand for effective and economic
      methods of phosphorus removal from treated water. The aim of this study was to
      evaluate the capacity for phosphorus removal of a microalgal biofilm during
      different light regimes. The photobioreactor was operated for nine months each
      year over a two-year period without interruption and without any need of re
      inoculation. The algal biofilm was able to remove 97 +/- 1% of total phosphorus
      from wastewater during 24 h of continuous artificial illumination. The average TP
      uptake rate in our experiments was 0.16 +/- 0.008 g m(-2) d(-1). Phosphorus
      removal values ranged from 36 to 41% when the algal biofilm was illuminated by
      natural light (12 h sunlight-12 h night). The biomass production rate was 12.21
      +/- 10 g dry weight m(-2) d(-1) in experiments with continuous artificial light
      and 5.6 +/- 1 g dry weight (DW) m(-2) d(-1) in experiments with natural light.
      These results indicate the great potential of microalgal biofilms in the tertiary
      treatment of wastewater. 

PMID- 25594826
TI  - Sarcopenic obesity with metabolic syndrome: a newly recognized entity following
      living donor liver transplantation.
AB  - OBJECTIVE: There are limited data about sarcopenic obesity in liver transplant
      recipients. METHODS: Living donor liver transplant recipients with at least 12
      months of follow-up were included. Metabolic syndrome (MS) was defined as >= 3
      ATP III criteria. Body composition was assessed by bioelectrical impedance.
      Immunosuppression protocol included short-term steroids, mycophenolate and
      calcineurin inhibitors (mainly tacrolimus). Data are shown as percentage, mean +/
      SD, or median (25-75 IQR). RESULTS: The study comprised 82 patients (males 69),
      aged 50.5 +/- 10.65 yr, and follow-up 24 (12-38.5) months. Etiology for cirrhosis
      was alcohol 29%, hepatitis C 22%, hepatitis B 17%, cryptogenic 24%, and others
      7%. Post-transplant sarcopenic obesity was present in 72 (88%), and MS was
      present in 43 (52%) of recipients with no significant difference among
      etiologies. There were significant differences between pre- and post-transplant
      body mass index, triglycerides, high-density lipoprotein, low-density lipoprotein
      (p = 0.000 for all), prevalence of hypertension (18% vs. 39%), and diabetes (20%
      vs. 56%). Patients with sarcopenic obesity had significantly higher body mass
      index, waist circumference, and MS (57% vs. 20%, p = 0.041) when compared to
      patients without sarcopenic obesity. CONCLUSION: Despite resuming routine
      activities, the majority of liver transplant recipients develop sarcopenic
      obesity and MS. The importance and role of appropriate nutrition and exercise
      after transplantation merits further investigation.

PMID- 25594827
TI  - Realization of in-source collision-induced dissociation in single-photon
      ionization time-of-flight mass spectrometry and its application for
      differentiation of isobaric compounds.
AB  - Single-photon ionization mass spectrometry (SPI-MS) is a versatile and powerful
      analytical technique for online and real-time analysis of organic species;
      however, it is confronted with an intrinsic drawback of lacking structural
      information on the investigated molecules, let alone differentiation of isobaric
      compounds. In this work, we describe a first attempt to integrate in-source
      collision-induced dissociation (CID) to the SPI ion source in a SPI-MS
      instrument. The in-source CID was accomplished by elevating the pressure in the
      ion source to medium vacuum pressure (MVP) and raising the extraction voltage.
      With the aid of in-source CID, both the SPI-induced molecular ion and CID
      generated fragment ion mass spectra can be obtained to endue each analyte with
      its unique spectrometric "fingerprint". The capability for differentiation of
      isobaric compounds is demonstrated by analyzing two groups of isobaric compounds
      with molecular weights of 72 and 106 Da, respectively, and quantitative analysis
      of p-xylene and ethylbenzene in gas mixture. As a result, isobaric compounds with
      different characteristic fragment ions or appearance energies can be successfully
      distinguished. The work presents a feasible method for practical applications of
      SPI-MS to differentiate isobaric compounds conveniently and rapidly without MS/MS
      technique or coupling additional separation technologies. 

PMID- 25594828
TI  - What causes addiction problems? Environmental, biological and constitutional
      explanations in press portrayals from four European welfare societies.
AB  - Press items (N = 1327) about addiction related problems were collected from
      politically independent daily newspapers in Finland, Italy, the Netherlands, and
      Poland from 1991, 1998, and 2011. A synchronized qualitative coding was performed
      for discerning the descriptions of the genesis to the problems in terms of
      described causes to and reasons for why they occur. Environmental explanations
      were by far the most common and they varied most between the materials. The
      analysis documents how the portrayals include traces of their contextual origin,
      relating to different media tasks and welfare cultural traditions. Meaning-based
      differences were also assigned to the kind of problems that held the most
      salience in the press reporting. A general worry over societal change is tied
      into the explanations of accumulating addiction problems and underpins the press
      reporting in all countries. 

PMID- 25594831
TI  - Connecting local active forces to macroscopic stress in elastic media.
AB  - In contrast with ordinary materials, living matter drives its own motion by
      generating active, out-of-equilibrium internal stresses. These stresses typically
      originate from localized active elements embedded in an elastic medium, such as
      molecular motors inside the cell or contractile cells in a tissue. While many
      large-scale phenomenological theories of such active media have been developed, a
      systematic understanding of the emergence of stress from the local force
      generating elements is lacking. In this paper, we present a rigorous theoretical
      framework to study this relationship. We show that the medium's macroscopic
      active stress tensor is equal to the active elements' force dipole tensor per
      unit volume in both continuum and discrete linear homogeneous media of arbitrary
      geometries. This relationship is conserved on average in the presence of
      disorder, but can be violated in nonlinear elastic media. Such effects can lead
      to either a reinforcement or an attenuation of the active stresses, giving us a
      glimpse of the ways in which nature might harness microscopic forces to create
      active materials. 

PMID- 25594830
TI  - Predictors of fluoroscopy time during percutaneous nephrolithotomy: impact of
      postgraduate urology trainees and S.T.O.N.E. nephrolithometry score.
AB  - OBJECTIVES: To determine predictors of fluoroscopy time (FT) during percutaneous
      nephrolithotomy (PCNL) and assess the impact of urology postgraduate trainees
      (PGTs) and S.T.O.N.E. nephrolithometry score. METHODS: A retrospective review of
      patients undergoing PCNL between 2010 and 2013 at a tertiary healthcare center
      was performed. Patients' demographics, stone characteristics, including
      S.T.O.N.E. nephrolithometry score, and operative data were compared among PGTs.
      Predictors of FT were determined using univariate and multivariate models.
      RESULTS: A total of 103 PCNLs were assisted by 10 PGTs from postgraduate years
      (PGYs) 4 and 5 (37 [35.9%] and 66 [64.1%] cases, respectively). Sixty percent of
      patients were males with a mean age of 55.2+/-1.5 years and a mean body mass
      index of 26.4+/-0.5 kg/m(2). The mean S.T.O.N.E. score was 7.7+/-0.1, with
      tubeless PCNL in 53 (51.5%) cases. The mean FT was 120+/-5 seconds, mean
      operative time was 102+/-3.5 minutes, and mean length of hospital stay was 4.2+/
      0.34 days. The overall stone-free rate was 72.8%. PGY-5 trainees used
      significantly less FT than PGY-4 trainees (115+/-6 seconds vs 130+/-7 seconds;
      p=0.04). FT significantly correlated with the number of involved calices (r=0.24;
      p=0.02), number of punctures (r=0.6; p=0.01), number of tracts (r=0.4; p=0.01),
      and operative time (r=0.4; p=0.01). In addition, cases with estimated blood loss
      (EBL) <250 mL were associated with significantly less FT than those with blood
      loss >250 mL (109+/-5.1 seconds vs 148.2+/-10.9 seconds; p=0.001). On
      multivariate analysis, the number of punctures, EBL, and operative time were
      found to be independent predictors for FT. However, there was no correlation of
      FT with the S.T.O.N.E. nephrolithometry score (r=0.16; p=0.1). CONCLUSIONS: The
      number of punctures, EBL, and operative time were the only independent predictors
      of prolonged FT during PCNL.

PMID- 25594829
TI  - Drinking reasons and alcohol problems by work venue among female sex workers in
      Guangxi, China.
AB  - OBJECTIVE: Alcohol use is a key determinant of sexual risk behaviors, but
      pathways to alcohol use in the context of commercial sex still remain unclear.
      The present study explores reasons for drinking and their roles on alcohol use
      problems among female sex workers (FSWs) in different types of commercial sex
      venues. METHOD: In 2009, a sample of 1,022 FSWs from Guangxi, China completed a
      survey containing a 10-item Alcohol Use Disorders Identification Test (AUDIT) and
      a 28-item measure of reasons for drinking. Factor analysis revealed five reasons
      for drinking: suppression, disinhibition, work requirement, sexual enhancement,
      and confidence booster. RESULTS: All identified reasons except confidence booster
      appeared to be related to a higher tendency of developing alcohol use problems
      among FSWs. Types of commercial sex venues moderated the relationship between
      work requirement and alcohol use problems. CONCLUSIONS: Alcohol-risk reduction
      interventions among this population need to provide them with alternative
      approaches to regulate emotions and modify their misconceptions about alcohol's
      sexual enhancing function. More attention is needed to FSWs' vulnerability to the
      negative influence of occupational drinking.

PMID- 25594832
TI  - Quantitative and qualitative adaptations of muscle fibers to glucocorticoids.
AB  - INTRODUCTION: The aim of this study was to understand the effects of short-term
      glucocorticoid administration in healthy subjects. METHODS: Five healthy men
      received dexamethasone (8 mg/day) for 7 days. Vastus lateralis muscle biopsy and
      knee extension torque measurement were performed before and after administration.
      A large number of individual muscle fibers were dissected from the biopsy samples
      (pre-administration: n = 165, post-administration: n = 177). RESULTS: Maximal
      knee extension torque increased after administration (~ 13%), whereas both type 1
      and type 2A fibers had decreased cross-sectional area (type 1: ~ 11%, type 2A: ~
      17%), myosin loss (type 1: ~ 18%, type 2A: ~ 32%), and loss of specific force
      (type 1: ~ 24%, type 2A: ~ 33%), which were preferential for fast fibers.
      CONCLUSION: Short-term dexamethasone administration in healthy subjects elicits
      quantitative and qualitative adaptations of muscle fibers that precede (and may
      predict) the clinical appearance of myopathy in glucocorticoid-treated subjects.

PMID- 25594833
TI  - Indole generates quiescent and metabolically active Escherichia coli cultures.
AB  - An inherent problem with bacterial cell factories used to produce recombinant
      proteins or metabolites is that resources are channeled into unwanted biomass as
      well as product. Over several years, attempts have been made to increase
      efficiency by unlinking biomass and product generation. One example was the
      quiescent cell (Q-Cell) expression system that generated non-growing but
      metabolically active Escherichia coli by over-expressing a regulatory RNA (Rcd)
      in a defined genetic background. Although effective at increasing the efficiency
      with which resources are converted to product, the technical complexity of the
      Rcd-based Q-Cell system limited its use. We describe here an alternative method
      for generating Q-Cells by the direct addition of indole, or related indole
      derivatives, to the culture medium of an E. coli strain carrying defined
      mutations in the hns gene. This simple and effective approach is shown to be
      functional in both shake-flask and fermenter culture. The cells remain
      metabolically active and analysis of their performance in the fermenter suggests
      that they may be particularly suitable for the production of cellular
      metabolites. 

PMID- 25594834
TI  - Comparison of organic matter composition in agricultural versus forest affected
      headwaters with special emphasis on organic nitrogen.
AB  - Agricultural management practices promote organic matter (OM) turnover and thus
      alter both the processing of dissolved organic matter (DOM) in soils and
      presumably also the export of DOM to headwater streams, which intimately connect
      the terrestrial with the aquatic environment. Size-exclusion chromatography, in
      combination with absorbance and emission matrix fluorometry, was applied to
      assess how agricultural land use alters the amount and composition of DOM, as
      well as dissolved organic nitrogen (DON) forms in headwater streams, including
      temporal variations, in a temperate region of NE Germany. By comparing six
      agriculturally and six forest-impacted headwater streams, we demonstrated that
      agriculture promotes increased DOC and DON concentrations, entailing an even more
      pronounced effect on DON. The major part of DOC and DON in agricultural and
      forest reference streams is exported in the form of humic-like material with high
      molecular weight, which indicates terrestrial, i.e., allochthonous sources. As an
      obvious difference in agricultural streams, the contribution of DOC and
      particularly DON occurring in the form of nonhumic high-molecular-weight,
      presumably proteinous material is clearly elevated. Altogether, DOM in
      agricultural headwaters is mainly complex-soil-derived and aromatic material with
      a low C:N ratio, which is more microbial processed than its counterpart from
      forest reference catchments. Our results emphasize the importance of agricultural
      land use on DOM loss from soils and identify agricultural soils as important DOC
      and particularly DON sources to headwater streams. 

PMID- 25594837
TI  - Steroid minimization immunosuppression protocol using basiliximab in adult living
      donor liver transplantation for hepatitis C virus-related cirrhosis.
AB  - AIM: Recent randomized trials have failed to prove the benefit of steroid-free
      immunosuppression in liver transplantation for hepatitis C virus (HCV)-related
      cirrhosis. Furthermore, there is a lack of data on the use of basiliximab in
      living donor liver transplantation (LDLT). This pilot study evaluated the safety
      and efficacy of a steroid minimization protocol using basiliximab compared with
      standard immunosuppression. METHODS: A single center, prospective cohort analysis
      was conducted to compare two immunosuppression regimens in adult recipients who
      underwent LDLT for HCV since 2004: calcineurin inhibitor/mizoribine/basiliximab
      (the St- group) and calcineurin inhibitor/mizoribine/steroid (the St+ group).
      Study end-points were rejection rates, recurrent HCV, patient survival and other
      adverse events up to 2 years after transplantation. RESULTS: A total of 27
      consecutive patients were enrolled. Transplantation characteristics were similar
      between the two groups (14 St- and 13 St+) except ABO incompatible cases being
      more common in the St+ group. Rejection rates, recurrent HCV, patient survival,
      fibrosis stage and new-onset diabetes mellitus at 2 years were comparable between
      the two groups. ABO incompatibility did not affect short- and long-term outcomes.
      Nine St- and seven St+ recipients underwent interferon and ribavirin therapy for
      recurrent HCV, with a sustained virological response rate of 33% and 29%,
      respectively. CONCLUSION: A steroid minimization protocol with basiliximab in
      adult LDLT for HCV is safe and affords equivalent rejection rates compared with
      standard immunosuppression. However, no significant differences are observed with
      respect to recurrent HCV, patient survival and metabolic complications.

PMID- 25594838
TI  - Cardiometabolic risk profile of participants with prediabetes diagnosed by HbA1c
      criteria in an urban Hong Kong Chinese population over 40 years of age.
AB  - AIMS: To investigate the usefulness of the additional measurement of HbA1c ,
      compared with performing only the oral glucose tolerance test (OGTT), in
      identifying participants at increased cardiometabolic risk, in an urban Chinese
      population. METHODS: All participants from the fourth visit of the population
      based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known
      diabetes, were included. All had their glycaemic status assessed by OGTT and
      HbA1c , according to American Diabetic Association 2010 criteria. RESULTS: Based
      on OGTT criteria alone, 3.5% of the study cohort (N = 1300) had diabetes and
      19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2%
      had prediabetes. The measurement of HbA1c , in addition to the OGTT, increased
      the proportion of participants with diabetes to 7.8% and with prediabetes to
      65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia (N =
      600) had waist circumference, systolic blood pressure, fasting glucose, insulin
      resistance index (HOMA-IR), Gutt Index and Framingham 10-year cardiovascular risk
      scores intermediate between those with both normal HbA1c and glycaemia (N = 350),
      and those with impaired fasting glucose and/or impaired glucose tolerance (N =
      249; all P < 0.01). CONCLUSION: The measurement of HbA1c in our population, in
      addition to the OGTT, results in the detection of a large number of participants
      with prediabetes having raised HbA1c but normal glycaemia who have a
      cardiometabolic risk profile intermediate between impaired fasting glucose and/or
      impaired glucose tolerance and normal participants, and would benefit from early
      lifestyle intervention.

PMID- 25594836
TI  - Cell penetrable human scFv specific to middle domain of matrix protein-1 protects
      mice from lethal influenza.
AB  - A new anti-influenza remedy that can tolerate the virus antigenic variation is
      needed. Influenza virus matrix protein-1 (M1) is highly conserved and pivotal for
      the virus replication cycle: virus uncoating, assembly and budding. An agent that
      blocks the M1 functions should be an effective anti-influenza agent. In this
      study, human scFv that bound to recombinant M1 middle domain (MD) and native M1
      of A/H5N1 was produced. Phage mimotope search and computerized molecular docking
      revealed that the scFv bound to the MD conformational epitope formed by
      juxtaposed helices 7 and 9 of the M1. The scFv was linked molecularly to a cell
      penetrable peptide, penetratin (PEN). The PEN-scFv (transbody), when used to
      treat the cells pre-infected with the heterologous clade/subclade A/H5N1 reduced
      the viral mRNA intracellularly and in the cell culture fluids. The transbody
      mitigated symptom severity and lung histopathology of the H5N1 infected mice and
      caused reduction of virus antigen in the tissues as well as extricated the
      animals from the lethal challenge in a dose dependent manner. The transbody
      specific to the M1 MD, either alone or in combination with the cognate human
      scFvs specific to other influenza virus proteins, should be an effective, safe
      and mutation tolerable anti-influenza agent. 

PMID- 25594840
TI  - Palpebral fissure length measurement: accuracy of the FAS facial photographic
      analysis software and inaccuracy of the ruler.
AB  - BACKGROUND: Accurate fetal alcohol spectrum disorder diagnoses require accurate
      facial measurement. The Fetal Alcohol Syndrome (FAS) Facial Photographic Analysis
      Software was developed to overcome measurement error known to occur with ruler
      measurement of the PFL. Recent publications have queried the Software's accuracy.
      OBJECTIVES: 1) Demonstrate the Software's ability to accurately measure a PFL
      from a 2-dimensional digital facial photograph. 2) Demonstrate the frequency and
      magnitude of error when the PFL is measured directly by clinicians using a ruler.
      METHODS: Objective 1: PFLs of mannequins were measured using the Software and a
      sliding digital caliper, with the latter serving as the gold-standard accurate
      measure. Mannequins allowed the caliper prongs to be placed directly on the
      landmarks that define the PFL. Objective 2: PFLs of 1,027 patients evaluated at
      the University of Washington FAS Diagnostic & Prevention Network were measured
      with the Software and directly by one or two clinicians using a ruler. RESULTS:
      Objective 1: The Software derived PFLs that were identical to or within 0.2 mm of
      the caliper measures. Objective 2: There was tremendous inter-rater variability
      in PFLs measured by clinicians using a hand held ruler. Seventy-seven percent of
      patients had their PFLs measured incorrectly (greater than 1 mm error) by at
      least one of the two clinicians using a ruler. CONCLUSION: The FAS Facial
      Photographic Analysis Software measures the PFL with the same accuracy as a
      sliding digital caliper, as it was programmed to do. Direct measurement of the
      PFL with a ruler is very prone to error.

PMID- 25594839
TI  - Low Pain Catastrophization and Disability Predict Successful Outcome to
      Radiofrequency Neurotomy in Individuals with Chronic Whiplash.
AB  - OBJECTIVES: Physical and psychological symptoms of individuals with chronic
      whiplash-associated disorders (WAD) are modulated by successful treatment with
      cervical radiofrequency neurotomy (cRFN). However, not all individuals respond to
      cRFN, and it is unknown which clinical features predict successful response to
      cRFN. METHODS: This prospective cohort study investigated 53 individuals with
      chronic WAD (36 female, 17 male; mean age = 44.7 +/- 10.9 (SD) years) who
      underwent cRFN. Predictor variables measured at baseline (prior to RFN) included
      self-reported pain (VAS), disability (NDI), post-traumatic stress symptoms (PDS),
      pain catastrophizing (PCS), and measures of sensory hypersensitivity (pressure
      and cold pain thresholds). The outcome measure was perceived Global Rating of
      Change (where scores >= 4 were classified as a successful response) 3 months post
      cRFN. RESULTS: Univariate logistic regression demonstrated that lower levels of
      disability and pain catastrophizing were associated with successful response of
      cRFN (both P < 0.05). Multivariable logistic regression demonstrated that low
      levels of pain catastrophizing and disability remained significant predictors of
      a successful response to cRFN (both P < 0.05). CONCLUSIONS: Low levels of pain
      catastrophizing and disability independently predicted a successful response to
      cRFN in patients with chronic WAD.

PMID- 25594841
TI  - (129) Xe and (131) Xe nuclear magnetic dipole moments from gas phase NMR spectra.
AB  - (3) He, (129) Xe and (131) Xe NMR measurements of resonance frequencies in the
      magnetic field B0=11.7586 T in different gas phase mixtures have been reported.
      Precise radiofrequency values were extrapolated to the zero gas pressure limit.
      These results combined with new quantum chemical values of helium and xenon
      nuclear magnetic shielding constants were used to determine new accurate nuclear
      magnetic moments of (129) Xe and (131) Xe in terms of that of the (3) He nucleus.
      They are as follows: MU((129) Xe) = -0.7779607(158)MUN and MU((131) Xe) =
      +0.6918451(70)MUN . By this means, the new 'helium method' for estimations of
      nuclear dipole moments was successfully tested. Gas phase NMR spectra demonstrate
      the weak intermolecular interactions observed on the (3) He and (129) Xe and
      (131) Xe shielding in the gaseous mixtures with Xe, CO2 and SF6 .

PMID- 25594842
TI  - Tracking changing X-ray contrast media application to an urban-influenced karst
      aquifer in the Wadi Shueib, Jordan.
AB  - Sewage input into a karst aquifer via leaking sewers and cesspits was
      investigated over five years in an urbanized catchment. Of 66 samples, analyzed
      for 25 pharmaceuticals, 91% indicated detectable concentrations. The former
      standard iodinated X-ray contrast medium (ICM) diatrizoic acid was detected most
      frequently. Remarkably, it was found more frequently in groundwater (79%, median:
      54 ng/l) than in wastewater (21%, 120 ng/l), which is supposed to be the only
      source in this area. In contrast, iopamidol, a possible substitute, spread over
      the aquifer during the investigation period whereas concentrations were two
      orders of magnitude higher in wastewater than in groundwater. Knowledge about
      changing application of pharmaceuticals thus is essential to assess urban impacts
      on aquifers, especially when applying mass balances. Since correlated
      concentrations provide conclusive evidence that, for this catchment, nitrate in
      groundwater rather comes from urban than from rural sources, ICM are considered
      useful tracers.

PMID- 25594835
TI  - Molecular biology of KSHV lytic reactivation.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) primarily persists as a latent
      episome in infected cells. During latent infection, only a limited number of
      viral genes are expressed that help to maintain the viral episome and prevent
      lytic reactivation. The latent KSHV genome persists as a highly ordered chromatin
      structure with bivalent chromatin marks at the promoter-regulatory region of the
      major immediate-early gene promoter. Various stimuli can induce chromatin
      modifications to an active euchromatic epigenetic mark, leading to the expression
      of genes required for the transition from the latent to the lytic phase of KSHV
      life cycle. Enhanced replication and transcription activator (RTA) gene
      expression triggers a cascade of events, resulting in the modulation of various
      cellular pathways to support viral DNA synthesis. RTA also binds to the origin of
      lytic DNA replication to recruit viral, as well as cellular, proteins for the
      initiation of the lytic DNA replication of KSHV. In this review we will discuss
      some of the pivotal genetic and epigenetic factors that control KSHV reactivation
      from the transcriptionally restricted latent program. 

PMID- 25594844
TI  - Fine-tuned h-ferritin nanocage with multiple gold clusters as near-infrared
      kidney specific targeting nanoprobe.
AB  - When stabilized and functionalized by biomolecules, noble metal (such as gold and
      silver) cluster-based hybrid nanocomposites have shown great promise for
      biomedical applications, due to their unique physiochemical properties
      originating from the inorganic elements and specific functionality and
      biocompatibility from their biological components. Although certain promise for
      bioimaging, biosensing, and biomimetic catalysis has been demonstrated, it is
      still a great challenge to integrate the defined functionality of the
      biomolecules with enhanced or novel physiochemical properties of the metal
      clusters, under control at the molecular level. Herein, based on molecular
      dynamics simulation of a gold (Au) cluster assembly, we designed near-infrared
      (NIR) fluorescent hybrid nanocomposites with multiple Au clusters within an apo H
      ferritin (HFt) nanocage. The fluorescence quantum yield of near-infrared (NIR) Au
      HFt is about 63.4% and the emission peak is 810 nm. The NIR Au-HFt is one of the
      first native protein-guided Au cluster-based nanomaterials for in vivo biowindow
      imaging. In vivo fluorescent imaging and quantification of Au element confirmed
      that Au-HFt not only retained the kidney targeting properties of HFt well (about
      10 times higher Au concentration in kidney than in liver and spleen, the most
      common organs for nanoparticle accumulation), but also gained strong NIR imaging
      capability for live animals. The NIR Au-HFt showed powerful tissue penetrating
      ability, strong fluorescent efficiency, and excellent kidney targeting
      specificity. These results thus open new opportunities for kidney disease imaging
      and theranostic applications. 

PMID- 25594843
TI  - Effect of transpiration on plant accumulation and translocation of PPCP/EDCs.
AB  - The reuse of treated wastewater for agricultural irrigation in arid and hot
      climates where plant transpiration is high may affect plant accumulation of
      pharmaceutical and personal care products (PPCPs) and endocrine disrupting
      chemicals (EDCs). In this study, carrot, lettuce, and tomato plants were grown in
      solution containing 16 PPCP/EDCs in either a cool-humid or a warm-dry
      environment. Leaf bioconcentration factors (BCF) were positively correlated with
      transpiration for chemical groups of different ionized states (p < 0.05).
      However, root BCFs were correlated with transpiration only for neutral PPCP/EDCs
      (p < 0.05). Neutral and cationic PPCP/EDCs showed similar accumulation, while
      anionic PPCP/EDCs had significantly higher accumulation in roots and
      significantly lower accumulation in leaves (p < 0.05). Results show that plant
      transpiration may play a significant role in the uptake and translocation of
      PPCP/EDCs, which may have a pronounced effect in arid and hot climates where
      irrigation with treated wastewater is common.

PMID- 25594845
TI  - Comparison of Moisturizing Creams for the Prevention of Atopic Dermatitis
      Relapse: A Randomized Double-blind Controlled Multicentre Clinical Trial.
AB  - Atopic dermatitis (AD) affects adults and children and has a negative impact on
      quality of life. The present multicentre randomized double-blind controlled trial
      showed a barrier-improving cream (5% urea) to be superior to a reference cream in
      preventing eczema relapse in patients with AD (hazard ratio 0.634, p = 0.011).
      The risk of eczema relapse was reduced by 37% (95% confidence interval (95% CI)
      10-55%). Median time to relapse in the test cream group and in the reference
      cream group was 22 days and 15 days, respectively (p = 0.013). At 6 months 26% of
      the patients in the test cream group were still eczema free, compared with 10% in
      the reference cream group. Thus, the barrier-improving cream significantly
      prolonged the eczema-free time compared with the reference cream and decreased
      the risk of eczema relapse. The test cream was well tolerated in patients with
      AD.

PMID- 25594847
TI  - A modular DNA origami-based enzyme cascade nanoreactor.
AB  - In this communication, we present a nanoscale reactor assembled from tuneable and
      spatially addressable tubular DNA origami units. We can controllably combine
      separate origami units equipped with glucose oxidase (GOx) and horseradish
      peroxidase (HRP), and demonstrate efficient GOx/HRP enzyme cascade reaction
      inside the tube. The reactor could be utilized as a nanoscale diagnostic tool,
      and modularity of the proposed system would further enable more complex
      reactions. 

PMID- 25594846
TI  - Stroke and pineal gland calcification: lack of association. Results from a
      population-based study (The Atahualpa Project).
AB  - OBJECTIVE: It has been suggested that pineal gland calcifications (PGC) represent
      a risk factor for stroke; however, information comes from a single retrospective
      hospital-based registry. We aimed to validate this association in a population
      based study conducted in rural Ecuador. METHODS: Atahualpa residents aged >=60
      years were identified during a door-to-door survey and invited to undergo
      neuroimaging studies (CT/MRI) for identification and rating PGC and lesions
      consistent with cerebral infarcts and hemorrhages. Cardiovascular health (CVH)
      status was assessed according to the American Heart Association criteria, and
      clinical strokes were identified by the use of a validated field instrument and
      confirmed by neurologists. RESULTS: Out of 248 participants (mean age 70+/-8
      years, 59% women, 73% with poor CVH), 137 (55%) had PGC and 39 (16%) had strokes
      (silent in 28 cases). PGC were noted in 61% versus 54% persons with and without
      stroke, respectively. After adjusting for age, sex and cardiovascular health,
      logistic and ordinal logistic regression models showed no association between any
      evidence (p=0.916) or severity (p=0.740) of PGC and stroke. CONCLUSION: PGC is
      not associated with stroke in this population of community-dwelling elders, where
      prevalence of PGC and stroke are similar to those found in other regions.

PMID- 25594848
TI  - Fabrication of high-resolution 4,8(2) -type archimedean nanolattices composed of
      solution processable spin cross-over Fe(II) metallosupramolecular polymers.
AB  - This paper presents the synthesis of two highly soluble Fe(II)
      metallosupramolecular polymers with two counter anions from a novel back-to-back
      coupled hybrid ligand. The spin cross-over (SCO) temperature of polymers with BF4
      and ClO4 counter anions is T1/2 = 313 K and T1/2 = 326 K, respectively. By
      following the top-down approach, one of the polymers (with ClO4 counter anion) is
      successfully solution processed using a lithographically controlled wetting
      technique to create laser readable high-resolution Archimedean (4,8(2) )
      nanolattices (consist of diamagnetic octagons and SCO squares). The thickness and
      top area of each SCO square are ~75 nm and ~2 * 2 MUm(2) , respectively. 

PMID- 25594849
TI  - The prelimbic cortex muscarinic M3 receptor-nitric oxide-guanylyl cyclase pathway
      modulates cardiovascular responses in rats.
AB  - The prelimbic cortex (PL), a limbic structure, sends projections to areas
      involved in the control of cardiovascular responses. Stimulation of the PL with
      acetylcholine (ACh) evokes depressor and tachycardiac responses mediated by local
      PL muscarinic receptors. Early studies demonstrated that stimulation of
      muscarinic receptors induced nitric oxide (NO) synthesis and cyclic guanosine
      cyclic monophosphate (cGMP) formation. Hence, this study investigates which PL
      muscarinic receptor subtype is involved in the cardiovascular response induced by
      ACh and tests the hypothesis that cardiovascular responses caused by muscarinic
      receptor stimulation in the PL are mediated by local NO and cGMP formation. PL
      pretreatment with J104129 (an M3 receptor antagonist) blocked the depressor and
      tachycardiac response evoked by injection of ACh into the PL. Pretreatment with
      either pirenzepine (an M1 receptor antagonist) or AF-DX 116 (an M2 and M4
      receptor antagonist) did not affect cardiovascular responses evoked by ACh.
      Moreover, similarly to the antagonism of PL M3 receptors, pretreatment with
      N(omega)-propyl-L-arginine (an inhibitor of neuronal NO synthase), carboxy
      PTIO(S)-3-carboxy-4-hydroxyphenylglicine (an NO scavenger), or 1H
      [1,2,4]oxadiazolol-[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor)
      blocked both the depressor and the tachycardiac response evoked by ACh. The
      current results demonstrate that cardiovascular responses evoked by
      microinjection of ACh into the PL are mediated by local activation of the M3
      receptor-NO-guanylate cyclase pathway.

PMID- 25594850
TI  - Role of Mig-6 in hepatic glucose metabolism.
AB  - BACKGROUND: Mitogen-inducible gene 6 (Mig-6) has an important role in the
      regulation of cholesterol homeostasis and bile acid synthesis. However, the
      physiological functions of Mig-6 in the liver remain poorly understood. METHODS:
      To investigate Mig-6 functioning in the liver, we used conditionally ablated Mig
      6 using the Albumin-Cre mouse model (Alb(cre/+) Mig-6(f/f) ; Mig-6(d/d) ). Male
      mice were killed after a 24-h fast and refed after 24 h fasting. Fasting glucose
      and insulin levels were measured and western blot analyses were performed to
      determine epidermal growth factor receptor (EGFR), extracellular signal-regulated
      kinase (ERK) 1/2, AKT, mammalian target of rapamycin (mTOR), c-Jun N-terminal
      kinase (JNK), and Insulin receptor substrate-1 (IRS-1) in liver tissue samples.
      In addition, human hepatocellular carcinoma HepG2 cells were transfected with Mig
      6 short interference (si) RNA before western blot analysis. RESULTS: Serum
      fasting glucose levels were significantly higher in Mig-6(d/d) versus Mig-6(f/f)
      mice. On an insulin tolerance test, insulin sensitivity was decreased in Mig
      6(d/d) versus Mig-6(f/f) mice. Furthermore, hepatic expression of the glucokinase
      (Gck), glucose-6-phosphatase (G6pc), and phosphoenolpyruvate carboxykinase 1
      (Pck1) genes was decreased significantly in Mig-6(d/d) mice. Phosphorylation of
      EGFR, ERK1/2, AKT, mTOR, JNK, and IRS-1 was increased in Mig-6(d/d) compared with
      Mig-6(f/f) mice. CONCLUSION: Liver-specific ablation of Mig-6 caused
      hyperglycemia by hepatic insulin resistance. Increased EGFR signaling following
      Mig-6 ablation activated JNK and eventually induced insulin resistance by
      increasing phosphorylation of IRS-1 at serine 307. This is the first report of
      Mig-6 involvement in hepatic insulin resistance and a new mechanism that explains
      hepatic insulin resistance.

PMID- 25594851
TI  - A biphasic response pattern of lipid metabolomics in the stage progression of
      hepatitis B virus X tumorigenesis.
AB  - Metabolic syndrome has closely linked to the development of human hepatocellular
      carcinoma (HCC). By using the hepatitis B virus (HBV) X (HBx) transgenic mouse
      model, we studied the dynamic evolution of serum and liver profiles of lipids and
      global cDNA expression at different stages of HBx tumorigenesis. We observed that
      the lipid (triglycerides, cholesterol, and fatty acids) profiles revealed a
      biphasic response pattern during the progression of HBx tumorigenesis: a small
      peak at early phase and a large peak or terminal switch at the tumor phase. By
      analyzing cDNA microarray data, the early peak correlated to the oxidative stress
      and pro-inflammatory response, which then resolved at the middle phase and were
      followed by the terminal metabolic switch in the tumor tissues. Five lipid
      metabolism-related genes, the arachidonate 5-lipoxygenase, lipoprotein lipase,
      fatty acid binding protein 4, 1-acylglycerol-3-phosphate O-acyltransferase 9, and
      apolipoprotein A-IV were identified to be significantly activated in HBx
      transgenic HCCs and further validated in human HBV-related HCCs. Inhibition of
      these lipid genes could reverse the effect of HBx on lipid biosynthesis and
      suppress HBx-induced cell proliferation in vitro. Our results support the concept
      that metabolic syndrome plays an important role in HBV tumorigenesis. The
      dysregulation of lipid metabolic genes may predict the disease progression to HCC
      in chronic hepatitis B patients.

PMID- 25594852
TI  - Mass spectrometry of protein complexes: from origins to applications.
AB  - Now routine is the ability to investigate soluble and membrane protein complexes
      in the gas phase of a mass spectrometer while preserving folded structure and
      ligand-binding properties. Several recent transformative developments have
      occurred to arrive at this point. These include advances in mass spectrometry
      instrumentation, particularly with respect to resolution; the ability to study
      intact membrane protein complexes released from detergent micelles; and the use
      of protein unfolding in the gas phase to obtain stability parameters. Together,
      these discoveries are providing unprecedented information on the compositional
      heterogeneity of biomacromolecules, the unfolding trajectories of multidomain
      proteins, and the stability imparted by ligand binding to both soluble and
      membrane-embedded protein complexes. We review these recent breakthroughs,
      highlighting the challenges that had to be overcome and the physicochemical
      insight that can now be gained from studying proteins and their assemblies in the
      gas phase. 

PMID- 25594853
TI  - Low-temperature kinetics and dynamics with Coulomb crystals.
AB  - Coulomb crystals-as a source of translationally cold, highly localized ions-are
      being increasingly utilized in the investigation of ion-molecule reaction
      dynamics in the cold regime. To develop a fundamental understanding of ion
      molecule reactions, and to challenge existing models that describe the rates,
      product branching ratios, and temperature dependence of such processes,
      investigators need to exercise full control over the experimental reaction
      parameters. This requires not only state selection of the reactants, but also
      control over the collision process (e.g., the collisional energy and angular
      momentum) and state-selective product detection. The combination of Coulomb
      crystals in ion traps with cold neutral-molecule sources is enabling the
      measurement of state-selective reaction rates in a diverse range of systems. With
      the development of appropriate product detection techniques, we are moving toward
      the ultimate goal of examining low-energy, state-to-state ion-molecule reaction
      dynamics. 

PMID- 25594854
TI  - Impact of anti-inflammatory therapies, xanthine oxidase inhibitors and other
      urate-lowering therapies on cardiovascular diseases in gout.
AB  - PURPOSE OF REVIEW: The purpose of this study is to give an overview of recently
      published articles covering the impact of anti-inflammatory therapies, xanthine
      oxidase inhibitors and other urate-lowering therapies on cardiovascular diseases
      in gout. RECENT FINDINGS: In patients with gout, long-term xanthine oxidase
      inhibition might reduce some cardiovascular comorbidities because of the dual
      effect of lowering serum uric acid levels and reducing free-radical production
      during uric acid formation. Among the anti-inflammatory therapies, colchicine has
      been shown to reduce some major cardiovascular events. SUMMARY: Epidemiological
      and experimental studies have shown that hyperuricaemia and gout are independent
      risk factors for cardiovascular diseases. The mechanisms that link high serum
      uric acid levels and gout with cardiovascular diseases are multifactorial,
      implicating low-grade systemic inflammation and xanthine oxidase activity as well
      as the deleterious effect of hyperuricaemia itself.

PMID- 25594856
TI  - Injury of the corticoreticular pathway in subarachnoid haemorrhage after rupture
      of a cerebral artery aneurysm.
AB  - OBJECTIVE: Several studies have reported on injury of the corticoreticular
      pathway in patients with stroke and traumatic brain injury. However, little is
      known about injury of the corticoreticular pathway in patients with subarachnoid
      haemorrhage. The aim of the current study was to investigate corticoreticular
      pathway injury in patients with subarachnoid haemorrhage. DESIGN: Comparative
      study. SUBJECTS: Among 137 patients with subarachnoid haemorrhage, 17 patients
      with motor weakness who showed intact integrity of the corticospinal tract were
      recruited. METHODS: Motricity Index was used for measurement of motor function.
      The fractional anisotropy value, apparent diffusion coefficient value, fibre
      volume, and integrity of the corticoreticular pathway were used for the diffusion
      tensor imaging parameters. RESULTS: Twelve (70.6%) of 17 patients and 18 (52.9%)
      of 34 hemispheres showed a discontinuation of the corticoreticular pathway at the
      midbrain level. The contralateral shoulder, hip, and lower extremity of the
      discontinued corticoreticular pathway showed lower motor functions, in comparison
      with those of the contralateral side of the intact corticoreticular pathway (p <
      0.05). By contrast, the Motricity Index for distal joint, upper and total
      Motricity Index were not different irrespective of the state of the
      corticoreticular pathway (p > 0.05). CONCLUSION: Corticoreticular pathway injury
      is common in patients with motor weakness after subarachnoid haemorrhage, and it
      appears to be related to weakness in the contralateral shoulder, hip and lower
      extremity.

PMID- 25594857
TI  - Kinetic ion thermometers for electron transfer dissociation.
AB  - Peptide fragment ions of the z-type were used as kinetic ion thermometers to
      gauge the internal energy of peptide cation-radicals produced by electron
      transfer in the gas-phase. Electron transfer dissociation (ETD)-produced z2 ions
      containing the leucine residue, z2(Leu-Lys) and z2(Leu-Arg), were found to
      undergo spontaneous dissociation by loss of C3H7 that was monitored by time
      resolved kinetic measurements on the time scale of the linear ion trap mass
      spectrometer. Kinetic modeling of the dissociations, including collisional
      cooling and product loss by neutralization, provided unimolecular rate constants
      for dissociation that were converted to the z ion internal energies using RRKM
      theory. The internal energy of z2(Leu-Lys) and z2(Leu-Arg) fragment ions was
      found to decrease with the increasing size of the precursor peptide ion,
      indicating vibrational energy partitioning between the ion and neutral fragments
      and ergodic behavior. The experimentally determined excitation in the peptide
      cation-radicals upon electron transfer (285-327 kJ mol(-1)) was found to be lower
      than that theoretically calculated from the reaction exothermicity. The reasons
      for this missing energy are discussed. 

PMID- 25594855
TI  - FCRL3 gene polymorphisms confer autoimmunity risk for allergic rhinitis in a
      Chinese Han population.
AB  - BACKGROUND: Heredity and environmental exposures may contribute to a
      predisposition to allergic rhinitis (AR). Autoimmunity may also involve into this
      pathologic process. FCRL3 (Fc receptor-like 3 gene), a novel immunoregulatory
      gene, has recently been reported to play a role in autoimmune diseases.
      OBJECTIVE: This study was performed to evaluate the potential association of
      FCRL3 polymorphisms with AR in a Chinese Han population. METHODS: Five single
      nucleotide polymorphisms of FCRL3, rs945635, rs3761959, rs7522061, rs10489678 and
      rs7528684 were genotyped in 540 AR patients and 600 healthy controls using a PCR
      restriction fragment length polymorphism assay. Allele, genotype and haplotype
      frequencies were compared between patients and controls using the chi2 test. The
      online software platform SHEsis was used to analyze their haplotypes. RESULTS:
      This study identified three strong risk SNPs rs7528684, rs10489678, rs7522061 and
      one weak risk SNP rs945635 of FCRL3 in Chinese Han AR patients. For rs7528684, a
      significantly increased prevalence of the AA genotype and A allele in AR patients
      was recorded. The frequency of the GG genotype and G allele of rs10489678 was
      markedly higher in AR patients than those in controls. For rs7522061, a higher
      frequency of the TT genotype, and a lower frequency of the CT genotype were found
      in AR patients. Concerning rs945635, a lower frequency of the CC genotype, and a
      higher frequency of G allele were observed in AR patients. According to the
      analysis of the three strong positive SNPs, the haplotype of AGT increased
      significantly in AR cases (AR = 38.8%, Controls = 24.3%, P = 8.29 * 10(-14), OR
      [95% CI] 1.978 [1.652~2.368]). CONCLUSIONS: This study found a significant
      association between the SNPs in FCRL3 gene and AR in Chinese Han patients. The
      results suggest these gene polymorphisms might be the autoimmunity risk for AR.

PMID- 25594858
TI  - Novel microdeletions affecting the GNAS locus in pseudohypoparathyroidism:
      characterization of the underlying mechanisms.
AB  - CONTEXT: Pseudohypoparathyroidism type Ia (PHP1A) is a rare endocrine disorder
      characterized by hypocalcemia, hyperphosphatemia, multiple hormonal resistance,
      and features of Albright hereditary osteodystrophy. When the phenotype is present
      but not associated with hormonal resistance, it is called
      psedopseudohypoparathyroidism (PPHP). Both entities have been associated to GNAS
      haploinsufficiency, and are mostly caused by inherited inactivating mutations at
      GNAS gene that codes for the stimulatory alpha subunit of G protein, although the
      cause remains unidentified in approximately 30% of patients. OBJECTIVES: The aims
      of our work were 1) to identify GNAS locus defects in 112 patients with clinical
      diagnosis of PHP1A/PPHP and no point mutations at GNAS, to improve molecular
      diagnostic and genetic counseling; 2) to outline the underlying molecular
      mechanism(s). METHODS: Methylation-specific-multiplex ligation-dependent probe
      amplification, qPCR, array comparative genomic hybridization, and long-PCR were
      used to search for genomic rearrangements at chromosome 20q and to identify their
      boundaries. We used different bioinformatic approaches to assess the involvement
      of the genomic architecture in the origin of the deletions. RESULTS: We
      discovered seven novel genomic deletions, ranging from 106-bp to 2.6-Mb. The
      characterization of five of seven deletion breakpoints and the definition of the
      putative molecular mechanisms responsible for these rearrangements revealed that
      Alu sequences play a major role in determining the genetic instability of the
      region. CONCLUSION: We observed that deletions at GNAS locus represent a
      significant cause of PPHP/PHP1A and that such defects are mostly associated with
      Alu-mediated recombination events. Their investigation revealed to be fundamental
      as, in some cases, they could be misdiagnosed as imprinting defects.

PMID- 25594859
TI  - Estrogen receptor alpha induces prosurvival autophagy in papillary thyroid cancer
      via stimulating reactive oxygen species and extracellular signal regulated
      kinases.
AB  - CONTEXT: The incidence of papillary thyroid cancer (PTC) shows a predominance in
      females, with a male:female ratio of 1:3, and none of the known risk factors are
      associated with gender difference. Increasing evidence indicates a role of
      estrogen in thyroid tumorigenesis, but the mechanism involved remains largely
      unknown. OBJECTIVE: This study aimed to assess the contribution of autophagy to
      estrogen receptor alpha (ERalpha)-mediated growth of PTC. DESIGN: The expression
      of ERalpha in thyroid tissue of patients with PTC tissues was analyzed. Cell
      viability, proliferation, and apoptosis were evaluated after chemical and genetic
      inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERalpha was
      assessed. RESULTS: ERalpha expression was increased in PTC tissues compared with
      the adjacent nontumor tissues. Estrogen induced autophagy in an ERalpha-dependent
      manner. Autophagy induced by estrogen/ERalpha is associated with generation of
      reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC
      cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor
      cell survival and promoted apoptosis, confirming the positive role of autophagy
      in the growth of PTC. CONCLUSIONS: ERalpha contributes to the growth of PTC by
      enhancing an important prosurvival catabolic process, autophagy, in PTC cells.
      The inhibition of autophagy promotes apoptosis, implicating a novel strategy for
      the treatment of ERalpha-positive PTC.

PMID- 25594860
TI  - PAPSS2 deficiency causes androgen excess via impaired DHEA sulfation--in vitro
      and in vivo studies in a family harboring two novel PAPSS2 mutations.
AB  - CONTEXT: PAPSS2 (PAPS synthase 2) provides the universal sulfate donor PAPS (3'
      phospho-adenosine-5'-phosphosulfate) to all human sulfotransferases, including
      SULT2A1, responsible for sulfation of the crucial androgen precursor
      dehydroepiandrosterone (DHEA). Impaired DHEA sulfation is thought to increase the
      conversion of DHEA toward active androgens, a proposition supported by the
      previous report of a girl with inactivating PAPSS2 mutations who presented with
      low serum DHEA sulfate and androgen excess, clinically manifesting with premature
      pubarche and early-onset polycystic ovary syndrome. PATIENTS AND METHODS: We
      investigated a family harboring two novel PAPSS2 mutations, including two
      compound heterozygous brothers presenting with disproportionate short stature,
      low serum DHEA sulfate, but normal serum androgens. Patients and parents
      underwent a DHEA challenge test comprising frequent blood sampling and urine
      collection before and after 100 mg DHEA orally, with subsequent analysis of DHEA
      sulfation and androgen metabolism by mass spectrometry. The functional impact of
      the mutations was investigated in silico and in vitro. RESULTS: We identified a
      novel PAPSS2 frameshift mutation, c.1371del, p.W462Cfs*3, resulting in complete
      disruption, and a novel missense mutation, c.809G>A, p.G270D, causing partial
      disruption of DHEA sulfation. Both patients and their mother, who was
      heterozygous for p.W462Cfs*3, showed increased 5alpha-reductase activity at
      baseline and significantly increased production of active androgens after DHEA
      intake. The mother had a history of oligomenorrhea and chronic anovulation that
      required clomiphene for ovulation induction. CONCLUSIONS: We provide direct in
      vivo evidence for the significant functional impact of mutant PAPSS2 on DHEA
      sulfation and androgen activation. Heterozygosity for PAPSS2 mutations can be
      associated with a phenotype resembling polycystic ovary syndrome.

PMID- 25594861
TI  - Evaluation of 451 Danish boys with delayed puberty: diagnostic use of a new
      puberty nomogram and effects of oral testosterone therapy.
AB  - CONTEXT: Few data exist on the diagnostic criteria, and on the effects of puberty
      induction, in boys with constitutional delay in growth and puberty (CDGP).
      OBJECTIVE: To develop puberty nomograms based on Danish boys with normal pubertal
      development. To evaluate the different diagnostic criteria and the effect of oral
      testosterone undecanoate (TU) in boys with CDGP. DESIGN: A cross-sectional and
      longitudinal study of Danish boys with normal pubertal development (COPENHAGEN
      puberty study). A retrospective observational study of 451 boys evaluated for
      delayed puberty between 1990 and 2013. SETTING: Tertiary referral center for
      pediatric endocrinology. PARTICIPANTS: One hundred and sixty-four (36%) boys
      evaluated for CDGP were excluded due to missing data, reclassification, or
      associated comorbidities, yielding 287 (64%) eligible for analysis. MAIN OUTCOME
      MEASURES: The number of patients with CDGP classified by the puberty nomogram
      (genital stage < -2 SD for age) versus the classical criteria (genital stage 1 at
      >= 14 years). The effect of one year of oral TU treatment on pubertal
      progression, circulating hormones, height, and predicted adult height (PAH).
      RESULTS: Seventy-eight (27%) of the 287 boys had delayed pubertal onset according
      to the classical criteria, whereas 173 (60%) of the 287 boys had impaired
      pubertal progression according to the puberty nomogram. Ninety-six (56%) of these
      173 boys were treated with oral TU for 0.8 years (0.5; 1.3) [median (25th; 75th
      percentiles)], which resulted in beneficial effects on pubertal progression.
      Height increased from -1.9 SD (-2.5; -1.2) to -1.5 SD (-2.1; -0.7) (P < .001),
      and PAH increased from 172.3 cm (170.3; 182.8) to 178.1 cm (171.4; 191.7) (P =
      .001) following one year of treatment. CONCLUSIONS: The puberty nomogram
      evaluates both delayed pubertal onset as well as delayed pubertal progression and
      allows separation of normal versus abnormal pubertal development. Oral TU
      treatment was followed by pubertal induction and progression and short-term
      growth without compromising final height.

PMID- 25594862
TI  - MEN1 disease occurring before 21 years old: a 160-patient cohort study from the
      Groupe d'etude des Tumeurs Endocrines.
AB  - CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only
      described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural
      history before 21 years old. METHODS: Obtain a description of the first symptoms
      occurring before 21 years old (clinical symptoms, biological or imaging
      abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs)
      occurring in a group of 160 patients extracted from the "Groupe d'etude des
      Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to
      hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%),
      nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases
      (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%),
      and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first
      lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22
      cases (14%) and before 5 years old in five cases (3%). Surgery was performed
      before age 21 in 66 patients (41%) with a total of 74 operations: pituitary
      adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%),
      NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET.
      One patient died before age 21 due to a thymic-NET. Overall, lesions were
      malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently
      before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors
      may develop at any age. Hyperparathyroidism was the most frequently encountered
      lesion but was not always the first biological or clinical abnormality to appear
      during the course of MEN1.

PMID- 25594863
TI  - Bone turnover markers predict bone mass development in young adult men: a five
      year longitudinal study.
AB  - CONTEXT: Peak bone mass is an important factor for the lifetime risk of
      developing osteoporosis. Ways to predict bone development in young adulthood are
      lacking. Objective and Main Outcome Measures: The aim of this study was to
      investigate whether baseline measurements of bone turnover markers could predict
      bone development in early adulthood in men. DESIGN, SETTING, AND PARTICIPANTS: In
      total, 817 men (age at baseline, 18.9 +/- 0.6 y; mean +/- SD) from the population
      based Gothenburg Osteoporosis and Obesity Determinants Study were included in
      this 5-year longitudinal study. Areal bone mineral density (aBMD) and bone
      mineral content (BMC) were measured using dual-energy x-ray absorptiometry, and
      volumetric BMD (vBMD) and cortical bone size were measured using peripheral
      quantitative computed tomography. Blood samples were collected at the baseline
      visit, and levels of osteocalcin (OC) and N-terminal telopeptide of type I
      collagen were analyzed. RESULTS: OC was a positive predictor of the increase in
      aBMD and BMC of the total body (R(2): aBMD, 6.6%; BMC, 4.9%), lumbar spine (R(2):
      aBMD, 5.4%; BMC, 5.7%), and radius (R(2): aBMD, 14.8%; BMC, 12.8%) between 19 and
      24 years (P < .001). Men in the highest OC quartile at baseline (35.2 +/- 4.4
      ng/mL; mean +/- SD) gained markedly more in radius cortical cross-sectional area
      (4.0 +/- 4.3 vs 1.9 +/- 2.9 mm(2)) and trabecular vBMD (11 +/- 7 vs 3 +/- 12
      mg/mm(3)) than men in the lowest OC quartile at baseline (17.7 +/- 2.3 ng/mL;
      mean +/- SD) (P < .001). CONCLUSION: A high OC level at the age of 19 predicts a
      favorable development in BMD, BMC, and bone size between 19 and 24 years of age.

PMID- 25594865
TI  - Microwave-assisted and gram-scale synthesis of ultrathin SnO2 nanosheets with
      enhanced lithium storage properties.
AB  - The rational design and fabrication of SnO2-based anode materials could offer a
      powerful way of effectively alleviating their large volume variation and
      guaranteeing excellent reaction kinetics for electrochemical lithium storage.
      Herein, we present an ultrarapid, low-cost, and simple microwave-assisted
      synthesis of ultrathin SnO2 nanosheets at the gram-scale. The two-dimensional
      (2D) anisotropic growth depends on microwave dielectric irradiation coupled with
      surfactant structural direction, and is conducted under low-temperature
      atmospheric conditions. The ultrathin 2D nanostructure holds a great surface tin
      atom percentage with high activity, where the electrochemical reaction processes
      could be facilitated that highly dependent on the surface. Compared with 1D SnO2
      nanorods, the ultrathin SnO2 nanosheets exhibit remarkably improved
      electrochemical lithium storage properties with a high reversible capacity of
      757.6 mAh g(-1) at a current density of 200 mA g(-1) up to 40 cycles as well as
      excellent rate capability and cycling stability. Specifically, the ultrathin 2D
      nanosheet could significantly reduce ion diffusion paths, thus allowing faster
      phase transitions, while the sufficient external surface interspace and interior
      porous configuration could successfully accommodate the huge volume changes. Even
      more importantly, we develop a promising strategy to produce ultrathin SnO2
      nanosheets to tackle their intrinsic problems for commercial applications. 

PMID- 25594864
TI  - Diabetic ketoacidosis in juvenile rats is associated with reactive gliosis and
      activation of microglia in the hippocampus.
AB  - BACKGROUND: Type 1 diabetes may be associated with structural and functional
      alterations in the brain. The role of diabetic ketoacidosis (DKA) in causing
      these alterations has not been well explored. METHODS: We used
      immunohistochemical staining to investigate cellular alterations in brain
      specimens from juvenile rats with DKA before, during, and after treatment with
      insulin and saline, and compared these to samples from diabetic rats and normal
      controls. RESULTS: Glial fibrillary acidic protein (GFAP) staining intensity was
      increased in the hippocampus during DKA and increased further during
      insulin/saline treatment. Twenty-four and 72 h after treatment, hippocampal GFAP
      intensity declined but remained above control levels. There were no significant
      changes in GFAP intensity in the cortex or striatum. OX42 staining intensity was
      increased during untreated DKA and increased further during insulin/saline
      treatment in the hippocampus and cortex. NeuN staining intensity was decreased
      after DKA treatment in the striatum but not in other regions. CONCLUSIONS: DKA
      causes inflammatory changes in the brain including reactive gliosis and
      activation of microglia. These findings are present during untreated DKA, but
      intensify during insulin/saline treatment. The hippocampus was disproportionately
      affected, consistent with previous studies showing deficits in hippocampal
      functions in rats after DKA recovery and decreased memory capacity in children
      with a history of DKA.

PMID- 25594866
TI  - Hybrid Single-Incision Laparoscopic Approaches for Endorectal Pull-Through in
      Hirschsprung's Disease.
AB  - BACKGROUND: Transanal endorectal pull-through for Hirschsprung's disease (HD) is
      a relatively safe and feasible procedure in neonates and infants. However,
      overstretching on the anal sphincter and mesentery of the sigmoid colon might
      cause potential risk of impaired defecation function. Single-incision
      laparoscopic endorectal pull-through (SILEP) is technically feasible and safe in
      HD patients, offering a better cosmetic result. However, it is stressful for the
      surgeon in view of its low manipulability and poor visualization causing clashing
      of instruments, especially in older children or patients with long-segment
      aganglionosis. We developed an age- and type-appropriate technique of hybrid
      SILEP (H-SILEP) using a trocarless instrument via another abdominal stab incision
      to obtain further improvement of SILEP in selected HD patients. PATIENTS AND
      METHODS: Between August 2010 and July 2013, 36 patients (24 boys and 12 girls,
      with a mean age of 3.9 months) with HD underwent H-SILEP. Patient age, gender,
      transitional zone, operative time, blood loss, and intraoperative and
      postoperative complications, as well as short- and long-term results, were
      assessed. RESULTS: Ten patients had transitional zone in the rectum, 17 patients
      in the sigmoid colon, and 9 patients in the descending colon. Neither additional
      ports nor conversion to laparotomy was required in these 36 patients. The mean
      operative time was 116 minutes. There was no major intraoperative complication.
      Perianal excoriation was the main early postoperative complication, which
      occurred in 9 patients. No anastomotic leak occurred. Postoperative enterocolitis
      occurred in 2 patients. There was no recurrent constipation. Follow-up for 6
      months to 3 years in all patients showed an excellent cosmetic result.
      CONCLUSIONS: Our procedure is feasible and safe, and it is technically less
      challenging to perform H-SILEP in selected HD patients. Moreover, it is better to
      use additional instruments for ergonometric reasons.

PMID- 25594867
TI  - Editorial.

PMID- 25594868
TI  - Dimensional Accuracy of Two-Step Impressions Measured on Scanned Casts in CAD.
AB  - PURPOSE: The purpose of the study was to find out how light-body impression
      material thickness influences the horizontal dimensional accuracy of casts
      examined on a scanned model. MATERIALS AND METHODS: Customized manikin mandibles
      were used for impression taking with a dual-phase impression method. These
      mandibles were prepared in a way that allowed the control of light-bodied
      impression material thickness. First premolars were prepared for a full crown by
      supragingival chamfer on both sides in all mandibles. For the measurements,
      buccal and lingual reference points were made at the preparation margin.
      Impressions were taken at nine thickness levels and a control level (TTotal = 10;
      0-1.2 mm), and the reference points' average distance was compared across
      thickness levels on both the left and right side. We carried out three measures
      for each specimen and used three specimens per thickness level. Total sample size
      was N = 180, creating a sizable database to understand the influence. RESULTS:
      The results indicated that light-body impression material thickness had no
      influence on the horizontal dimension of a die measured on scanned dies in these
      specific circumstances. CONCLUSIONS: The thickness of light-body impression
      material in the dual-phase impression taking technique did not have a significant
      influence on the horizontal accuracy of scanned dies, which makes the technique
      safe and reliable for single crown restorations without having to take extra
      precautions for the thickness of light-body impression material.

PMID- 25594869
TI  - Insight into strain effects on band alignment shifts, carrier localization and
      recombination kinetics in CdTe/CdS core/shell quantum dots.
AB  - The impact of strain on the optical properties of semiconductor quantum dots
      (QDs) is fundamentally important while still awaiting detailed investigation.
      CdTe/CdS core/shell QDs represent a typical strained system due to the
      substantial lattice mismatch between CdTe and CdS. To probe the strain-related
      effects, aqueous CdTe/CdS QDs were synthesized by coating different sized CdTe QD
      cores with CdS shells upon the thermal decomposition of glutathione as a sulfur
      source under reflux. The shell growth was carefully monitored by both steady
      state absorption and fluorescence spectroscopy and transient fluorescence
      spectroscopy. In combination with structural analysis, the band alignments as a
      consequence of the strain were modified based on band deformation potential
      theory. By further taking account of these strain-induced band shifts, the
      effective mass approximation (EMA) model was modified to simulate the electronic
      structure, carrier spatial localization, and electron-hole wave function overlap
      for comparing with experimentally derived results. In particular, the
      electron/hole eigen energies were predicted for a range of structures with
      different CdTe core sizes and different CdS shell thicknesses. The overlap of
      electron and hole wave functions was further simulated to reveal the impact of
      strain on the electron-hole recombination kinetics as the electron wave function
      progressively shifts into the CdS shell region while the hole wave function
      remains heavily localized in CdTe core upon the shell growth. The excellent
      agreement between the strain-modified EMA model with the experimental data
      suggests that strain exhibits remarkable effects on the optical properties of
      mismatched core/shell QDs by altering the electronic structure of the system. 

PMID- 25594870
TI  - Medication supply for people evacuated during disasters.
AB  - Medication loss is a major problem in disaster settings, and it is crucial for
      patients to bring their medication and healthcare items with them when they leave
      their homes during an evacuation. This article is based on a systematic
      literature review on medication loss, the objectives of which were to identify
      the extent and implications of medication loss, to identify the burden of
      prescription refill, and to make recommendations on effective preparedness. The
      review revealed that medication loss, prescription loss and refills, and the loss
      of medical aids are a significant burden on the medical relief teams. The medical
      aids are not limited to drugs, but include routine medications, medical/allergy
      records, devices for specific care and daily life, and emergency medications. One
      possible solution is to make a personal emergency pack and for people to carry
      this with them at all times. To ensure that patients are adequately prepared,
      stakeholders, especially health professionals, need to be actively involved in
      the preparation plans. Since our findings have little impact on disaster risk
      reduction unless shared broadly, we are now taking actions to spread our
      findings, such as presenting in conferences and via posters, in order to raise
      awareness among patients and healthcare professionals. As part of these
      activities, our findings were presented at the Evidence Aid Symposium on 20
      September 2014, at Hyderabad, India. 

PMID- 25594875
TI  - Adeno-associated virus vector-based gene therapy for monogenetic metabolic
      diseases of the liver.
AB  - Liver-based metabolic diseases account for a substantial burden of childhood
      diseases. In most patients, treatment is often limited to supportive measures and
      liver transplantation is ultimately required. Even despite the excellent long
      term outcome of liver transplantation, the procedure is associated with a
      significant morbidity and mortality. Gene therapy, in contrast, has great
      potential to save lives, improve the quality of life, and offer few risks and
      adverse effects compared with present therapies including liver transplantation.
      The most promising results to date in liver gene transfer have been achieved with
      adeno-associated virus. Although safety issues, such as immunogenicity of vector
      and/or transgene product, remain an important concern, gene therapy is ready for
      clinical trials in adults and adolescents. Developing and testing safe approaches
      for efficient and long-term stable applications in newborns and small children,
      such as targeted integration and gene correction, is one of the remaining future
      challenges. 

PMID- 25594873
TI  - Non-classical gluconeogenesis-dependent glucose metabolism in Rhipicephalus
      microplus embryonic cell line BME26.
AB  - In this work we evaluated several genes involved in gluconeogenesis, glycolysis
      and glycogen metabolism, the major pathways for carbohydrate catabolism and
      anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and
      catalytic control of the genes and enzymes associated with these pathways are
      modulated by alterations in energy resource availability (primarily glucose).
      BME26 cells in media were investigated using three different glucose
      concentrations, and changes in the transcription levels of target genes in
      response to carbohydrate utilization were assessed. The results indicate that
      several genes, such as glycogen synthase (GS), glycogen synthase kinase 3 (GSK3),
      phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6 phosphatase (GP)
      displayed mutual regulation in response to glucose treatment. Surprisingly, the
      transcription of gluconeogenic enzymes was found to increase alongside that of
      glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In
      addition, RNAi data from this study revealed that the transcription of
      gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these
      results improve our understanding of how glucose metabolism is regulated at the
      genetic level in tick cells. 

PMID- 25594874
TI  - Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of
      tacrolimus at early stage post-renal transplantation.
AB  - While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus
      therapy, the predictive capability of genetic information for dosing at early
      stage post-renal transplantation is unknown. We investigated the influence of
      polymorphisms over time. An initial oral dose of modified-release once-daily
      tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal
      transplant patients every 24 h. Stepwise multiple linear regression analysis for
      tacrolimus dosing was performed each week to determine the effect of patient
      clinical characteristics. The dose-adjusted trough concentration was
      approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the
      CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78
      1.17) vs. 0.59 (0.45-0.87) ng/mL/mg; p < 0.001). The contribution of genetic
      factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from
      Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and
      28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus
      maintenance dosage became evident after Day 14 post-transplantation, although the
      tacrolimus dosage was determined based only on patient body weight for the first
      three days after surgery. Tacrolimus dosage starting with the initial
      administration should be individualized using the CYP3A5 genotype information. 

PMID- 25594872
TI  - Specificity protein 1 regulates gene expression related to fatty acid metabolism
      in goat mammary epithelial cells.
AB  - Specificity protein 1 (SP1) is a ubiquitous transcription factor that plays an
      important role in controlling gene expression. Although important in mediating
      the function of various hormones, the role of SP1 in regulating milk fat
      formation remains unknown. To investigate the sequence and expression
      information, as well as its role in modulating lipid metabolism, we cloned SP1
      gene from mammary gland of Xinong Saanen dairy goat. The full-length cDNA of the
      SP1 gene is 4376 bp including 103 bp of 5'UTR, 2358 bp of ORF (HM_236311) and
      1915 bp of 3'UTR, which is predicted to encode a 786 amino acids polypeptide.
      Phylogenetic tree analysis showed that goat SP1 has the closest relationship with
      sheep, followed by bovines (bos taurus, odobenus and ceratotherium), pig,
      primates (pongo, gorilla, macaca and papio) and murine (rattus and mus), while
      the furthest relationship was with canis and otolemur. Expression was predominant
      in the lungs, small intestine, muscle, spleen, mammary gland and subcutaneous
      fat. There were no significant expression level differences between the mammary
      gland tissues collected at lactation and dry-off period. Overexpression of SP1 in
      goat mammary epithelial cells (GMECs) led to higher mRNA expression level of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) and lower liver X
      receptor alpha (LXRalpha) mRNA level, both of which were crucial in regulating
      fatty acid metabolism, and correspondingly altered the expression of their
      downstream genes in GMECs. These results were further enhanced by the silencing
      of SP1. These findings suggest that SP1 may play an important role in fatty acid
      metabolism. 

PMID- 25594876
TI  - Terpyridine-based heteroditopic ligand for Ru(II)Ln3(III) metallostar
      architectures (Ln = Gd, Eu, Nd, Yb) with MRI/optical or dual-optical responses.
AB  - A new ditopic ligand (L) based on a 2,2':5',4"-terpyridine unit substituted in
      the 2",6" positions with iminodiacetate arms has been designed and synthesized
      for the construction of Ru(II)L3Ln3(III) supramolecular architectures. The two
      components of this system, a 2,2'-bipyridine unit for Ru(II) coordination and a
      pyridine-bis(iminodiacetate) core for Ln(III) coordination, are tightly connected
      via a covalent Carom(py)-Carom(py) bond. The paramagnetic and photophysical
      properties of the corresponding tetrametallic Ru(II)L3Gd3(III) complex have been
      evaluated, highlighting the potential of this metallostar structure to act as a
      bimodal MRI/optical imaging agent. Variable-temperature (17)O NMR and proton
      nuclear magnetic relaxation dispersion (NMRD) measurements showed that this
      complex exhibits (i) a remarkable relaxivity per metallostar molecule,
      particularly at clinical and high magnetic fields (r1(310K) = 51.0 and 36.0 mM(
      1) s(-1) at 20 and 300 MHz, respectively) and (ii) a near-optimal residence
      lifetime of Gd(III) coordinated water molecule (tauM(310K) = 77.5 ns). This is
      the result of the presence of two inner-sphere water molecules in the Gd(III)
      components of the metallostar and a slow tumbling rate of the molecule
      (tauR(310K) = 252 ps). Upon excitation in the visible domain (lambdaexc = 472
      nm), the Ru(II) component of the complex exhibits a bright-red luminescence
      centered at 660 nm with a quantum yield of 2.6% in aqueous solutions at pH 7.4.
      Moreover, this Ru(II)L3Gd3(III) assembly is also characterized by a high kinetic
      inertness in biological media (PBS and human serum solutions) and a high
      photostability (photobleaching). Finally, preliminary photophysical studies on
      RuL3Nd3 and RuL3Yb3 assemblies revealed that the Ru(II) center acts as an
      effective sensitizer for Ln(III)-based luminescence in the near-IR region. The
      Nd(III) species was found to be the most effective at quenching the (3)MLCT
      luminescence of the Ru center. 

PMID- 25594877
TI  - Can a barcode scanner for blood collection improve patient identification
      integrity in the emergency department? A prospective before-and-after study.
AB  - OBJECTIVE: To describe the effect of interventions designed to improve patient
      identification (PI) during pathology collection in the ED. METHODS: A prospective
      before-and-after intervention study was conducted between June 2009 and June 2010
      in a regional ED in Queensland, Australia. Interventions aimed to improve PI and
      specimen labelling, and consisted of: (i) education alone; and (ii) education
      plus an armband scanner that voice-prompted collector behaviour. Main outcomes
      measured included: frequency of correct key behaviours (KBs) during specimen
      collection, pathology integrity errors and cost of interventions. RESULTS: Data
      from 282 ED pathology collections were analysed (before: n = 115, after with
      education: n = 95, after with education plus armband scanner: n = 72). KBs for PI
      and labelling improved significantly following education plus armband scanner
      use. Application of armbands before sample collection increased (36% vs 90%, P <
      0.001), as did asking the patient to state their name (25% vs 93%, P < 0.001) and
      date of birth (22% vs 93%, P < 0.001). These results were similar, albeit less
      pronounced, when the effect of education only was assessed. No primary patient
      misidentification was detected in this small study. The annual costs for a
      hospital to adopt the education programme with and without the armband scanner
      were $104,045 and $5330 respectively. CONCLUSION: ED staff had poor behaviours
      for identifying patients and labelling pathology specimens before intervention.
      These safety behaviours were considered an assumed skill. Education alone
      improved critical KBs markedly that was further augmented by the armband scanner.
      The cost to adopt education alone is relatively low compared to the addition of
      armband scanner technology.

PMID- 25594878
TI  - Systematic strategy for designing immidazolium containing precursors to produce N
      heterocyclic carbenes: a DFT study.
AB  - A series of cationic N-heterocyclic carbene (NHC) precursors that can be utilized
      as fluorescent chemosensors for carbon dioxide capture were investigated by
      density functional theory (DFT) calculations. Activation energy barriers for the
      reactions of the cationic NHC precursors and hydrogen carbonate (HCO3(-)) based
      on intrinsic reaction coordinate (IRC) profiles as well as proton affinity of the
      precursors were compared. The calculated proton affinity of 1-ethyl-3
      methylimidazol-2-yliene was in good agreement with experimental one within the
      margin of error. We clarified main factors to lower the activation energy barrier
      based on the correlation among the number of N-heterocyclic functional group,
      aromatic ring size, and structural characteristics for the candidate compounds.
      On the basis of the results, it was verified that some of our model systems
      spontaneously generate NHCs without any specific catalyst. 

PMID- 25594871
TI  - Cellular disulfide bond formation in bioactive peptides and proteins.
AB  - Bioactive peptides play important roles in metabolic regulation and modulation
      and many are used as therapeutics. These peptides often possess disulfide bonds,
      which are important for their structure, function and stability. A systematic
      network of enzymes--a disulfide bond generating enzyme, a disulfide bond donor
      enzyme and a redox cofactor--that function inside the cell dictates the formation
      and maintenance of disulfide bonds. The main pathways that catalyze disulfide
      bond formation in peptides and proteins in prokaryotes and eukaryotes are
      remarkably similar and share several mechanistic features. This review summarizes
      the formation of disulfide bonds in peptides and proteins by cellular and
      recombinant machinery.

PMID- 25594879
TI  - Lethal and sub-lethal effects of faecal deltamethrin residues on dung-feeding
      insects.
AB  - Endectocides administered to livestock to facilitate pest and parasite control
      may be excreted in the faeces at concentrations that are toxic to coprophagous
      insects, including species of ecological importance. Although much research has
      focused on the effects of macrocyclic lactones, relatively less attention has
      been given to any similar impacts of the widely used pyrethroid insecticides.
      Here, the effects of faecal residues of the pyrethroid deltamethrin after
      application to Holstein-Friesian cattle in a proprietary pour-on formulation are
      examined. Freshly dropped dung was collected 1, 3, 5 and 7 days after treatment
      and from an untreated control group. In laboratory bioasssays, female Lucilia
      sericata (Diptera: Calliphoridae) blow flies matured significantly smaller egg
      batches and had a lower percentage of eggs hatch after feeding on dung collected
      for up to 5 days after treatment, compared with flies feeding on dung from
      untreated cattle. In the field, artificial dung pats were constructed from the
      collected dung and left on pastureland for 7 days before being retrieved and
      searched for insects. Significantly more adult Diptera emerged from the faeces of
      untreated cattle than from the dung of treated cattle collected on days 1 and 3
      after treatment. Adult Coleoptera were found in lower numbers in the dung of
      treated animals compared with control dung, suggesting a repellent effect. The
      results indicate that deltamethrin residues in cattle faeces have a range of
      lethal and sub-lethal effects on dung-feeding insects for up to a week after
      treatment, but that the precise duration and nature of toxicity varies depending
      on the sensitivity of the insect in question.

PMID- 25594880
TI  - Developmental dyslexia.
AB  - This review uses a levels-of-analysis framework to summarize the current
      understanding of developmental dyslexia's etiology, brain bases, neuropsychology,
      and social context. Dyslexia is caused by multiple genetic and environmental risk
      factors as well as their interplay. Several candidate genes have been identified
      in the past decade. At the brain level, dyslexia is associated with aberrant
      structure and function, particularly in left hemisphere reading/language
      networks. The neurocognitive influences on dyslexia are also multifactorial and
      involve phonological processing deficits as well as weaknesses in other oral
      language skills and processing speed. We address contextual issues such as how
      dyslexia manifests across languages and social classes as well as what treatments
      are best supported. Throughout the review, we highlight exciting new research
      that cuts across levels of analysis. Such work promises eventually to provide a
      comprehensive explanation of the disorder as well as its prevention and
      remediation. 

PMID- 25594881
TI  - Facile synthesis of hairy core-shell structured magnetic polymer submicrospheres
      and their adsorption of bovine serum albumin.
AB  - Highly magnetic polymer submicrospheres with a hairy core-shell structure were
      facilely synthesized by combining distillation-precipitation polymerization (DPP)
      with subsequent surface-initiated atom transfer radical polymerization (SI-ATRP),
      and then investigated for protein adsorption. A robust polymer shell consisting
      of poly(divinylbenzene-co-chloromethylstyrene) (P(DVB-co-CMS)) was coated on
      superparamagnetic submicrometer-sized magnetite colloid nanocrystal clusters
      (MCNCs) via DPP. With the benzyl chloride groups on the shell as initiator,
      poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) hairs were grafted by SI
      ATRP approach. The resulting hairy core-shell structured Fe3O4@ P(DVB-co-CMS)
      PDMAEMA microspheres showed pH- and temperature-sensitivity, and high
      magnetization. The composite microspheres were further investigated for
      adsorption of a typical acidic protein, i.e. bovine serum albumin (BSA). They
      exhibited a high binding capacity up to over 660 mg/g (corresponding to 158
      DMAEMA monomer units cooperating for binding one BSA molecule) and could rapidly
      reach binding equilibrium within 5 min. Moreover, the adsorption of BSA was found
      to be remarkably dependent on the pH and salt concentration of the protein
      solutions, and the bound protein could be quantitatively desorbed by washing with
      a medium with lowered pH or raised salt concentration.

PMID- 25594882
TI  - Modelling the interfacial behaviour of dilute light-switching surfactant
      solutions.
AB  - The direct molecular modelling of an aqueous surfactant system at concentrations
      below the critical micelle concentration (pre-cmc) conditions is unviable in
      terms of the presently available computational power. Here, we present an
      alternative that combines experimental information with tractable simulations to
      interrogate the surface tension changes with composition and the structural
      behaviour of surfactants at the water-air interface. The methodology is based on
      the expression of the surface tension as a function of the surfactant surface
      excess, both in the experiments and in the simulations, allowing direct
      comparisons to be made. As a proof-of-concept a coarse-grained model of a light
      switching non-ionic surfactant bearing a photosensitive azobenzene group is
      considered at the air-water interface at 298 K. Coarse-grained molecular dynamic
      simulations are detailed based on the use of the SAFT force field with parameters
      tuned specifically for this purpose. An excellent agreement is obtained between
      the simulation predictions and experimental observations; furthermore, the
      molecular model allows the rationalization of the macroscopic behaviour in terms
      of the different conformations of the cis and trans surfactants at the surface.

PMID- 25594884
TI  - Effects of auxiliary ligands of Pd(II) dimers on induction of chiral nematic
      phases: chirality inversion and the photo-responsive structural change.
AB  - Dinuclear square planar palladium(ii) complexes, [{Pd(ii)La}2(baet)] (La(-) =
      beta-diketonato and baet(2-) = 1,2-diacetyl-1,2-bis(3-methylbutanoyl)ethanato),
      were prepared and used as chiral dopants to induce chiral nematic phases. The
      following beta-diketones were used as LaH: pentane-2,4-dione (acacH),
      dibenzoylmethane (dbmH), di-4-nonyloxybenzoylmethane (C9-dbmH) and 3-[4'-(4''
      (octyloxy)phenylazo)phenyl]-2,4-dione (C8-azoacacH). When the enantiomers were
      doped in a nematic liquid crystal, they induced a chiral nematic phase with a
      helical twisting power (HTP) of 5-50 MUm(-1). In particular, the sample doped
      with [{Pd(ii)(C8-azoacac)}2(baet)] exhibited a reversible change of the circular
      dichroism spectrum under alternate irradiation at 350 nm and 460 nm. It implied
      that the HTP changed reversibly in response to the cis-trans isomerization of the
      coordinated C8-azoacac ligand. 

PMID- 25594883
TI  - Rapid adsorption of 2,4-dichlorophenoxyacetic acid by iron oxide nanoparticles
      doped carboxylic ordered mesoporous carbon.
AB  - The ordered mesoporous carbon composite functionalized with carboxylate groups
      and iron oxide nanoparticles (Fe/OMC) was successfully prepared and used to
      adsorb 2,4-dichlorophenoxyacetic acid (2,4-D) from wastewater. The resultant
      adsorbent possessed high degree of order, large specific surface area and pore
      volume, and good magnetic properties. The increase in initial pollutant
      concentration and contact time would make the adsorption capacity increase, but
      the pH and temperature are inversely proportional to 2,4-D uptake. The
      equilibrium of adsorption was reached within 120 min, and the equilibrated
      adsorption capacity increased from 99.38 to 310.78 mg/g with the increase of
      initial concentration of 2,4-D from 100 to 500 mg/L. Notablely, the adsorption
      capacity reached 97% of the maximum within the first 5 min. The kinetics and
      isotherm study showed that the pseudo-second-order kinetic and Langmuir isotherm
      models could well fit the adsorption data. These results indicate that Fe/OMC has
      a good potential for the rapid adsorption of 2,4-D and prevention of its further
      diffusion.

PMID- 25594885
TI  - Magnetic plasmonic Fano resonance at optical frequency.
AB  - Plasmonic Fano resonances are typically understood and investigated assuming
      electrical mode hybridization. Here we demonstrate that a purely magnetic plasmon
      Fano resonance can be realized at optical frequency with Au split ring hexamer
      nanostructure excited by an azimuthally polarized incident light. Collective
      magnetic plasmon modes induced by the circular electric field within the hexamer
      and each of the split ring can be controlled and effectively hybridized by
      designing the size and orientation of each ring unit. With simulated results
      reproducing the experiment, our suggested configuration with narrow line-shape
      magnetic Fano resonance has significant potential applications in low-loss
      sensing and may serves as suitable elementary building blocks for optical
      metamaterials. 

PMID- 25594887
TI  - Prebiotics, probiotics, synbiotics, and the immune system: experimental data and
      clinical evidence.
AB  - PURPOSE OF REVIEW: The intestinal immune system is constantly exposed to foreign
      antigens, which for the most part should be tolerated. Certain probiotics,
      prebiotics, and synbiotics are able to influence immune responses. In this
      review, we highlight the recent publications (within the last 2 years) that have
      substantially progressed this field. RECENT FINDINGS: The immunological
      mechanisms underpinning probiotics, prebiotics, and synbiotics effects continue
      to be better defined with novel mechanisms being described for dendritic cells,
      epithelial cells, T regulatory cells, effector lymphocytes, natural killer T
      cells, and B cells. Many of the mechanisms being described are bacterial strain
      or metabolite specific, and should not be extrapolated to other probiotics or
      prebiotics. In addition, the timing of intervention seems to be important, with
      potentially the greatest effects being observed early in life. SUMMARY: In this
      review, we discuss the recent findings relating to probiotics, prebiotics, and
      synbiotics, specifically their effects on immunological functions.

PMID- 25594886
TI  - Validation and important differences for the Sarcoidosis Assessment Tool. A new
      patient-reported outcome measure.
AB  - RATIONALE: Patient-reported outcome (PRO) measures have been developed to measure
      symptoms and other aspects of health-related quality of life. OBJECTIVES: The
      Sarcoidosis Assessment Tool (SAT), a sarcoidosis-specific PRO, was administered
      in a lung and skin sarcoidosis treatment trial. We explored SAT performance
      characteristics and correlation with standard clinical measurements to validate
      it as a useful clinical sarcoidosis-specific PRO. METHODS: The SAT analyses
      focused on baseline and Week 16 assessments. Besides the SAT, participants
      underwent clinical and physician assessments plus additional PROs that were used
      as anchor variables and were compared with the SAT. Reliability was evaluated by
      using Cronbach alpha coefficient. Spearman correlation coefficients were used to
      evaluate the association between SAT scores with clinical and other PRO measures.
      Changes between assessments in the clinical and PRO "anchor" variables were
      classified as improved, stable, or worsened. Mean differences between adjacent
      categories of the known groups and mean changes from the ability to detect change
      analyses were reviewed for appropriate clinically important difference estimates.
      MEASUREMENTS AND MAIN RESULTS: Results from 173 patients were analyzed. Each SAT
      module reflected appropriate anchor variables at baseline and in terms of change.
      The Cronbach alpha for each of these modules was at least 0.87. In addition, we
      successfully established a clinically important difference range for each SAT
      module. CONCLUSIONS: We demonstrated that the SAT is a reliable and consistent
      sarcoidosis-specific PRO. It has excellent internal consistency and reliability.
      A range of clinically important differences has been established for the SAT
      modules. Clinical trial registered with www.clinicaltrials.gov (NCT 00955279).

PMID- 25594888
TI  - Distinct management issues with Crohn's disease of the small intestine.
AB  - PURPOSE OF REVIEW: Small bowel Crohn's disease can present with clinical
      challenges that are specific to its location. In this review, we address some of
      the areas that present particular problems in small bowel Crohn's disease. RECENT
      FINDINGS: A key issue specific to small bowel Crohn's disease relates to its
      diagnosis given that access to the small bowel is limited. Radiological advances,
      particularly in small bowel ultrasonography and MRI, as well as the introduction
      of capsule endoscopy and balloon enteroscopy are helping to address this. In
      addition, our ability to differentiate small bowel Crohn's disease from other
      causes of inflammation, such as tuberculosis, is improving on the basis of better
      understanding of the features that differentiate these conditions. It is also
      becoming apparent that jejunal Crohn's disease represents a distinct disease
      phenotype with potentially worse clinical outcomes. Finally, because it is a rare
      complication, our understanding of small bowel cancer associated with Crohn's
      disease remains limited. Recent publications are, however, starting to improve
      our knowledge of this condition. SUMMARY: Although small bowel Crohn's disease
      presents specific management issues not seen in patients with Crohn's disease
      elsewhere in the gastrointestinal tract, our knowledge of how to manage these is
      improving.

PMID- 25594889
TI  - Genetic and epigenetic basis of psoriasis pathogenesis.
AB  - Psoriasis is a chronic inflammatory skin disease whose prevalence varies among
      different populations worldwide. It is a complex multi-factorial disease and the
      exact etiology is largely unknown. Family based studies have indicated a genetic
      predisposition; however they cannot fully explain the disease pathogenesis. In
      addition to genetic susceptibility, environmental as well as gender and age
      related factors were also been found to be associated. Recently, imbalances in
      epigenetic networks are indicated to be causative elements in psoriasis. The
      present knowledge of epigenetic involvement, mainly the DNA methylation,
      chromatin modifications and miRNA deregulation is surveyed here. An integrated
      approach considering genetic and epigenetic anomalies in the light of
      immunological network may explore the pathogenesis of psoriasis. 

PMID- 25594890
TI  - Viral RNA detection by RIG-I-like receptors.
AB  - In higher vertebrates, recognition of the non-self signature of invading viruses
      by genome-encoded pattern recognition receptors initiates antiviral innate
      immunity. Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) detect
      viral RNA as a non-self pattern in the cytoplasm and activate downstream
      signaling. Detection of viral RNA also activates stress responses resulting in
      stress granule-like aggregates, which facilitate RLR-mediated antiviral immunity.
      Among the three RLR family members RIG-I and melanoma differentiation-associated
      gene 5 (MDA5) recognize distinct viral RNA species with differential molecular
      machinery and activate signaling through mitochondrial antiviral signaling (MAVS,
      also known as IPS-1/VISA/Cardif), which leads to the expression of cytokines
      including type I and III interferons (IFNs) to restrict viral propagation. In
      this review, we summarize recent knowledge regarding RNA recognition and signal
      transduction by RLRs and MAVS/IPS-1. 

PMID- 25594891
TI  - Curcumin-based anti-prostate cancer agents.
AB  - Prostate cancer possesses the highest occurrence rate and is the second-paramount
      disease that causes cancer-affiliated death among men in the United States.
      Approximately 30,000 men die each year of castration-resistant prostate cancer
      due to the inevitable progression of resistance to first-line treatment with
      docetaxel. The safety profile of dietary curcumin in humans has been well
      documented, and its therapeutic prospect in treating prostate cancer, especially
      for castration-resistant prostate cancer, has been evidenced in several cell
      culture systems and human xenograft mouse models. The critical disadvantage of
      curcumin as a drug candidate is its low bioavailability caused by poor water
      solubility and rapid in vivo metabolism. Curcumin is characteristic of regulating
      multiple targets, representing a good example for the philosophy to search for
      multitargeted drugs in the realm of drug design and drug development. This
      feature, together with its potential in treating castration-resistant prostate
      cancer and its safety profile, enables curcumin to serve as an ideal lead
      compound for the design and syntheses of curcumin-based agents with improved
      potential for the clinical therapies of prostate cancer. Several researches
      aiming to improve its bioavailability and potency resulted in the discovery and
      development of a wealth of curcumin-based compounds with an enhanced anticancer
      potential and/or an improved pharmacokinetic profile. This review starts with a
      brief summarization of the prospect of curcumin in treating prostate cancer and
      its mechanisms of action, then provides an in-depth overview of current
      development of curcumin-based anti-prostate cancer agents and their structure
      activity relationships, and ends with the syntheses and pharmacokinetic studies
      of curcumin.

PMID- 25594892
TI  - Liposome encapsulated all trans retinoic acid (ATRA) has enhanced
      immunomodulatory and inflammation reducing activities in mice model.
AB  - The all trans retinoic acid (ATRA) is found to have a promising regulatory effect
      on immune system and inflammatory responses in experimental research. The purpose
      of this study was to investigate whether this therapeutic efficiency of ATRA
      could be enhanced by encapsulating into a liposome formulation composed of
      Distearoyl-L-phosphatidylcholine (DSPC) and cholesterol utilizing a well
      established mice model. The humoral antibody titer (HA), delayed-type
      hypersensitivity (DTH), bone marrow cellularity, hematology, and levels of alpha-
      esterase-positive cells, were taken as parameters to assess the level of
      immunomodulation in the sheep red blood cells (SRBC) immunized and challenged
      BALB/c mice. The anti-inflammatory effect of encapsulated ATRA was evaluated by
      the size changes in the induced inflammation edema in the mice paw as well as its
      histopathology. The results showed a significant immunostimulatory effect for
      both the free and encapsulated ATRA as indicated by the increase in the levels of
      total leukocyte, bone marrow and alpha-esterase positive cells and decreased Hb
      level respectively. We have also observed an enhanced specific antibody
      hemagglutinin titre value and the DTH response developed in response to SRBC
      challenge in these treatments. Both the immunostimulatory as well as inflammation
      reducing property were significantly higher in encapsulated ATRA treated group of
      mice over that of in free ATRA treated group of mice. Based on these results, we
      conclude that the encapsulated ATRA has a higher potency over free ATRA in its
      immunomodulatory activity and also has a significant impact on reducing
      inflammation in BALB/c mice model.

PMID- 25594893
TI  - Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite
      PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study.
AB  - Efficacy assessments using a combination of ibrutinib and lenalidomide
      necessitate the development of an analytical method for determination of both
      drugs in plasma with precision. A high performance liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method was developed for the simultaneous
      determination of lenalidomide, ibrutinib, and its active metabolite PCI45227 in
      rat plasma. Extraction of lenalidomide, ibrutinib, PCI45227 and tolbutamide
      (internal standard; IS) from 50 MUl rat plasma was carried out by liquid-liquid
      extraction with ethyl acetate:dichloromethane (90:10) ratio. Chromatographic
      separation of analytes was performed on YMC pack ODS AM (150 mm * 4.6 mm, 5 MUm)
      column under gradient conditions with acetonitrile:0.1% formic acid buffer as the
      mobile phases at a flow rate of 1 ml/min. Precursor ion and product ion
      transition for analytes and IS were monitored on a triple quadrupole mass
      spectrometer, operated in the selective reaction monitoring with positive
      ionization mode. Method was validated over a concentration range of 0.72-183.20
      ng/ml for ibrutinib, 0.76-194.33 ng/ml for PCI-45227 and 1.87-479.16 ng/ml for
      lenalidomide. Mean extraction recovery for ibrutinib, PCI-45227, lenalidomide and
      IS of 75.2%, 84.5%, 97.3% and 92.3% were consistent across low, medium, and high
      QC levels. Precision and accuracy at low, medium and high quality control levels
      were less than 15% across analytes. Bench top, wet, freeze-thaw and long term
      stability was evaluated for all the analytes. The analytical method was applied
      to support a pharmacokinetic study of simultaneous estimation of lenalidomide,
      ibrutinib, and its active metabolite PCI-45227 in Wistar rat. Assay
      reproducibility was demonstrated by re-analysis of 18 incurred samples.

PMID- 25594894
TI  - First characterisation of flavonoid- and diarylheptanoid-type antioxidant
      phenolics in Corylus maxima by HPLC-DAD-ESI-MS.
AB  - Corylus maxima Mill. (Betulaceae) leaves have been used in traditional medicine
      both internally and externally, nevertheless phytochemical exploration of the
      plant remains incomplete. In this study, the in vitro antioxidant activity and
      polyphenolic composition of the ethyl acetate and methanolic extracts of C.
      maxima leaves and bark are reported for the first time. The radical scavenging
      activities of the extracts were investigated by the ABTS and DPPH assays. All the
      extracts of C. maxima possessed notable antioxidant activity. By mean of a HPLC
      DAD-ESI-TOF and a HPLC-DAD-ESI-MS/MS method, altogether twenty-two phenolics were
      tentatively characterised: one flavan derivative (1), seven flavonol derivatives
      (4, 6, 12, 13, 16, 20 and 21) and fourteen diarylheptanoids (2, 3, 5, 7-11, 14,
      15, 17-19 and 22). The amount of the two main flavonoids - myricetin-3-O
      rhamnoside (6) and quercetin-3-O-rhamnoside (13) - and two diarylheptanoids -
      oregonin (3) and hirsutenone (15) - in the extracts were determined by a
      validated HPLC-ESI-MS/MS method in multiple reaction monitoring (MRM) mode. Our
      results showed that C. maxima could be considered as a valuable source of
      pharmacologically important natural products that might contribute to the
      revaluation of the phytotherapeutical potential of the plant. 

PMID- 25594895
TI  - Isolation, LC-MS/MS and 2D-NMR characterization of alkaline degradants of
      tenofovir disoproxil fumarate.
AB  - The present work describes the preparative isolation and characterization of two
      alkaline degradation products of tenofovir disoproxil fumarate (TDF). Tenofovir
      disoproxil is a prodrug of tenofovir (antiviral agent) and co-crystal form of
      this prodrug with fumaric acid is tenofovir disoproxil fumarate. The drug is
      subjected to alkaline degradation with 0.1N sodium hydroxide for 2 min at room
      temperature. The two degradants were detected by high performance liquid
      chromatography (HPLC) at relative retention of 0.26 and 0.73 with respect to the
      drug. HPLC method involves gradient elution on Kromasil Eternity column (150 mm *
      2.1 mm, 2.5 MUm) using ammonium acetate (10mM) - acetonitrile as mobile phase at
      flow rate of 0.3 mL/min and UV detection at 260 nm. Two degradation products were
      isolated by preparative HPLC and further characterized by LC-MS, (1)H NMR, (13)C
      NMR and 2D-NMR. On the basis of this spectral data, the structure of two DPs are
      confirmed as methyl hydrogen ({[1-(6-amino-9H-purin-9-yl)propan-2
      yl]oxy}methyl)phosphonate for DP-I and dimethyl ({[1-(6-amino-9H-purin-9
      yl)propan-2-yl]oxy}methyl)phosphonate for DP-II.

PMID- 25594896
TI  - A validated liquid chromatography tandem mass spectrometry method for
      quantification of erlotinib, OSI-420 and didesmethyl erlotinib and semi
      quantification of erlotinib metabolites in human plasma.
AB  - A liquid chromatography tandem mass spectrometry method was developed and
      validated for quantification of erlotinib and its metabolites in human plasma.
      The method is suitable for therapeutic drug monitoring and pharmacokinetic
      studies. The substances were extracted using protein precipitation, separated on
      a BEH XBridge C18 column (100 *2.1 mm, 1.7 MUm) by gradient elution at 0.7 mL/min
      of acetonitrile and 5 mM ammonium acetate. The concentration was determined using
      a Waters Xevo triple quadrupole mass spectrometer in a multi reaction monitoring
      mode. The total run time was 7 min. Deuterated erlotinib and OSI-597 were used as
      internal standard for erlotinib and its metabolites, respectively. Erlotinib, OSI
      420 and didesmethyl erlotinib were quantified in the concentration range 25-5000
      ng/mL, 0.5-500 ng/mL and 0.15-10 ng/mL, respectively. Precision and accuracy was
      <14% except for OSI-420 at LLOQ (17%). Extraction recovery was above 89%, 99% and
      89% for erlotinib, OSI-420 and didesmethyl erlotinib, respectively. The human
      liver microsomes generated 14 metabolites, three of them not previously reported.
      Twelve metabolites were measured semi-quantitatively and validated with respect
      to selectivity, precision and stability.

PMID- 25594897
TI  - Development of analytical method for ultrasensitive detection of salbutamol
      utilizing DNA labeled-immunoprobe.
AB  - Salbutamol (SAL) is known as quick-acting beta-2 receptor agonist and its use in
      humans for pulmonary diseases and/or in animal feed is limited because of
      associated potential hazardous effects on health. Several techniques are
      available for the detection of SAL, but are expensive and time consuming. Here
      for the first time, a novel pre-assembled DNA immunoprobe-based immuno-PCR assay
      was developed to investigate the levels of SAL in human urine samples and
      compared the proposed immuno-PCR assay for the detection of SAL with that of
      direct competitive ELISA. Under the optimized conditions, the assay showed a
      linear range over seven orders of magnitude, whereas the limit of detection of
      SAL in buffer was found to be 21 fg/mL. Current immuno-PCR assay exhibited a 300
      fold better detection limit for SAL as compared to one achieved with direct
      competitive ELISA using the same antibody. In conclusion, it has been found that
      the developed method is highly sensitive and simple method that can significantly
      enhance the detection sensitivity for small molecules. Moreover it can be
      modified and used for detecting other small molecules and/or chemicals that exist
      in the environment and are responsible for the environmental pollution.

PMID- 25594898
TI  - The complete microspeciation of ovothiol A disulfide: a hexabasic symmetric
      biomolecule.
AB  - The site-specific acid-base properties of ovothiol A disulfide (OvSSOv), the
      smallest hexabasic multifunctional biomolecule with complex interdependent
      moieties, were studied with (1)H NMR-pH and potentiometric titrations. The
      unprecedented complexity of the protonation microequilibria could be overcome by
      taking into account the mirror-image molecular symmetry, synthesizing and
      studying auxiliary model compounds and developing a custom-tailored evaluation
      method. The amino, imidazole, and carboxylate moieties are quantified in terms of
      192 microscopic protonation constants and 64 microspecies, 96 and 36 of which are
      chemically different ones, respectively. Nine pairwise interactivity parameters
      also characterize the OvSSOv-proton system at the level of molecular subunits.
      These data allow understanding and influencing the co-dependent acid-base and
      redox properties of the highly complex OvSH-OvSSOv and related thiol-disulfide
      systems, which provide protection against oxidative stress. This work is the
      first complete microspeciation of a hexabasic molecule. 

PMID- 25594901
TI  - Update in lung cancer: prologue to a modern review series.

PMID- 25594899
TI  - A novel, simple and inexpensive procedure for the simultaneous determination of
      iopamidol and p-aminohippuric acid for renal function assessment from plasma
      samples in awake rats.
AB  - The purpose of the current study was to design, validate and implement a novel
      analytical method for the simultaneous plasma measurement of iopamidol and p
      aminohippuric acid (PAH) to estimate renal function in awake rats. A reverse
      phase high performance liquid chromatographic (RP-HPLC) method for the
      simultaneous measurement of iopamidol (for glomerular filtration rate estimation,
      GFR) and PAH (for tubular secretion determination, TS) was designed and validated
      using a C-18 column, 0.1M acetic acid-10% acetonitrile (90:10, v/v) as mobile
      phase, at a flow rate of 0.3 ml/min, and UV detection at 270 nm. Iopamidol (244.8
      mg/kg) was administered intravenously followed immediately by sodium PAH (100
      mg/kg) to healthy female Sprague-Dawley rats. Plasma samples obtained at 2.5, 5,
      10, 15, 20, 30, 45, 60, 90, and 120 min after drug administration were
      deproteinized with 2.5% trichloroacetic acid containing p-aminobenzoic acid as
      internal standard, and separated by the validated RP-HPLC method described above.
      The iopamidol and PAH chromatographic data were analyzed using a non
      compartmental model. The results demonstrated that the RP-HPLC method was linear
      in ranges between 15-120 MUg/ml and 2.5-120 MUg/ml for iopamidol and PAH,
      respectively. Precision and accuracy were within 15% for both drugs. Recovery of
      iopamidol and PAH was 92% and 100%, respectively. Plasma iopamidol and PAH
      clearances in awake rats, estimates for GFR and TS, respectively, were 1.49+/
      0.20 ml/min and 3.73+/-0.38 ml/min. In conclusion, the method here described is a
      simple and reliable procedure, for the simultaneous and time-saving determination
      of GFR and TS from plasma samples in the conscious rat.

PMID- 25594902
TI  - Implementation of modern therapy approaches and research for non-small cell lung
      cancer in Japan.
AB  - The genetic backgrounds of the Japanese (or Asians) are, at least in part,
      different from those of Caucasians. It is necessary to recognize this difference
      to develop medicine that is both optimized and individualized. In particular, the
      consideration of ethnic differences is becoming increasingly important for lung
      cancer medicine. Japanese clinical practice guidelines indicate that some
      clinical biomarkers, such as epidermal growth factor receptor gene mutations,
      echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase
      fusion gene and uridine diphosphate glucuronosyltransferase genotypes should be
      determined in appropriate lung cancer patients. At the present time, tests for
      these biomarkers are covered by the Japanese national health-care programme, as
      is treatment with certain targeted drugs and cytotoxic agents. Therefore, most
      patients with lung cancer in Japan receive these tests as part of daily practice
      if their performance status and organ function are judged to be eligible. In
      addition, ethnic differences in bone marrow toxicity caused by cytotoxic drugs
      are reflected in treatment choice, and the requirements for the development of
      treatment modalities suitable for rare targeted populations are also increasing.
      To meet these requirements, many collaborative groups in Japan that have improved
      their infrastructure for investigator-initiated trials and conducted important
      activities need to provide further optimal treatment modalities for Japanese and
      Asian patients with lung cancer. Here, the characteristics of lung cancer in
      Japanese patients, general aspects of medical treatment and the care system in
      Japan, and representative studies on lung cancer in Japan are reviewed. 

PMID- 25594905
TI  - SCORE: a novel multi-criteria decision analysis approach to assessing the
      sustainability of contaminated land remediation.
AB  - The multi-criteria decision analysis (MCDA) method provides for a comprehensive
      and transparent basis for performing sustainability assessments. Development of a
      relevant MCDA-method requires consideration of a number of key issues, e.g. (a)
      definition of assessment boundaries, (b) definition of performance scales, both
      temporal and spatial, (c) selection of relevant criteria (indicators) that
      facilitate a comprehensive sustainability assessment while avoiding double
      counting of effects, and (d) handling of uncertainties. Adding to the complexity
      is the typically wide variety of inputs, including quantifications based on
      existing data, expert judgements, and opinions expressed in interviews. The SCORE
      (Sustainable Choice Of REmediation) MCDA-method was developed to provide a
      transparent assessment of the sustainability of possible remediation alternatives
      for contaminated sites relative to a reference alternative, considering key
      criteria in the economic, environmental, and social sustainability domains. The
      criteria were identified based on literature studies, interviews and focus-group
      meetings. SCORE combines a linear additive model to rank the alternatives with a
      non-compensatory approach to identify alternatives regarded as non-sustainable.
      The key strengths of the SCORE method are as follows: a framework that at its
      core is designed to be flexible and transparent; the possibility to integrate
      both quantitative and qualitative estimations on criteria; its ability, unlike
      other sustainability assessment tools used in industry and academia, to allow for
      the alteration of boundary conditions where necessary; the inclusion of a full
      uncertainty analysis of the results, using Monte Carlo simulation; and a
      structure that allows preferences and opinions of involved stakeholders to be
      openly integrated into the analysis. A major insight from practical application
      of SCORE is that its most important contribution may be that it initiates a
      process where criteria otherwise likely ignored are addressed and openly
      discussed between stakeholders. 

PMID- 25594903
TI  - Bridged filaments of histone-like nucleoid structuring protein pause RNA
      polymerase and aid termination in bacteria.
AB  - Bacterial H-NS forms nucleoprotein filaments that spread on DNA and bridge
      distant DNA sites. H-NS filaments co-localize with sites of Rho-dependent
      termination in Escherichia coli, but their direct effects on transcriptional
      pausing and termination are untested. In this study, we report that bridged H-NS
      filaments strongly increase pausing by E. coli RNA polymerase at a subset of
      pause sites with high potential for backtracking. Bridged but not linear H-NS
      filaments promoted Rho-dependent termination by increasing pause dwell times and
      the kinetic window for Rho action. By observing single H-NS filaments and
      elongating RNA polymerase molecules using atomic force microscopy, we established
      that bridged filaments surround paused complexes. Our results favor a model in
      which H-NS-constrained changes in DNA supercoiling driven by transcription
      promote pausing at backtracking-susceptible sites. Our findings provide a
      mechanistic rationale for H-NS stimulation of Rho-dependent termination in
      horizontally transferred genes and during pervasive antisense and noncoding
      transcription in bacteria. 

PMID- 25594906
TI  - Flash floods in the Tatra Mountain streams: frequency and triggers.
AB  - Flash floods represent a frequently recurring natural phenomenon in the Tatra
      Mountains. On the northern slopes of the mountain chain, located in Poland,
      ongoing and expected future changes in climate are thought to further increase
      the adverse impacts of flash floods. Despite the repeat occurrence of major
      floods in the densely populated foothills of the Polish Tatras, the headwaters
      have been characterized by a surprising lack of data, such that any analysis of
      process variability or hydrometeorological triggers has been largely hampered so
      far. In this study, dendrogeomorphic techniques have been employed in four poorly
      gauged torrential streams of the northern slope of the Tatra Mountains to
      reconstruct temporal and spatial patterns of past events. Using more than 1100
      increment cores of trees injured by past flash floods, we reconstruct 47 events
      covering the last 148 years and discuss synoptic situations leading to the
      triggering of flash floods with the existing meteorological and flow gauge data.
      Tree-ring analyses have allowed highlighting the seasonality of events, providing
      new insights about potential hydrometeorological triggers as well as a
      differentiating flash flood activity between catchments. Results of this study
      could be useful to design future strategies to deal with flash flood risks at the
      foothills of the Polish Tatras and in the Vistula River catchment.

PMID- 25594907
TI  - Body burden of cadmium and its related factors: a large-scale survey in China.
AB  - A survey of more than 6000 participants from four distinct non-polluted and
      polluted regions in China was conducted to evaluate the body burden of cadmium
      (Cd) on the Chinese populations using urinary Cd (UCd) as a biomarker. The
      findings revealed that the UCd level was 1.24 MUg/g creatinine (MUg/g cr) for the
      sample population from non-polluted Shanghai, and the UCd levels exceeded 5 MUg/g
      cr, which is the health-based exposure limit set by the World Health Organization
      (WHO), in 1.1% of people. The mean UCd levels in moderately polluted (Hubei and
      Liaoning) and highly polluted areas (Guizhou) were 4.69 MUg/g cr, 3.62 MUg/g cr
      and 6.08 MUg/g cr, respectively, and these levels were 2.9 to 4.9 times the
      levels observed in Shanghai. Notably, the UCd levels exceeded the recently
      updated human biomonitoring II values (i.e., intervention or "action level") in
      44.8%-87.9% of people from these areas compared to only 5.1%-21.4% of people in
      Shanghai. The corresponding prevalence of elevated UCd levels (>WHO threshold, 5
      MUg/g cr) was also significantly higher (30.7% to 63.8% vs. 1.1%), which
      indicates that elevated Cd-induced health risks to residents in these areas. Age
      and region were significant determinants for UCd levels in a population, whereas
      gender did not significantly influence UCd.

PMID- 25594909
TI  - Predesign and systematic synthesis of 11 highly porous coordination polymers with
      unprecedented topology.
AB  - We propose and validate a simple strategy of vertex connection that can be used
      for framework design and pore size/type modulation to prepare a mother structure
      and another 10 highly porous isoreticular frameworks with unprecedented topology.
      Importantly, the potential accessible pore volumes (57-71%), pore sizes (6.8-11.
      2 A; 17.0-29.0 A; 12.5-22.8 A; 11.9-24.5 A), and the pore shapes of this series
      of highly porous frameworks were simultaneously and systematically tuned.
      Interestingly, the pore size of IIa [Zn4O(L(2))2(BDC)0.5]{(CH3)2NH2} decreased a
      little less than that of IIc [Zn4O(L(2))2(2,6-NDC)0.5]{(CH3)2NH2}; however, its
      selectivity of CO2 toward CH4 increased by almost two times. 

PMID- 25594904
TI  - The contrasting phylodynamics of human influenza B viruses.
AB  - A complex interplay of viral, host, and ecological factors shapes the spatio
      temporal incidence and evolution of human influenza viruses. Although
      considerable attention has been paid to influenza A viruses, a lack of equivalent
      data means that an integrated evolutionary and epidemiological framework has
      until now not been available for influenza B viruses, despite their significant
      disease burden. Through the analysis of over 900 full genomes from an
      epidemiological collection of more than 26,000 strains from Australia and New
      Zealand, we reveal fundamental differences in the phylodynamics of the two co
      circulating lineages of influenza B virus (Victoria and Yamagata), showing that
      their individual dynamics are determined by a complex relationship between virus
      transmission, age of infection, and receptor binding preference. In sum, this
      work identifies new factors that are important determinants of influenza B
      evolution and epidemiology. 

PMID- 25594908
TI  - Phenotypic plasticity and epithelial-to-mesenchymal transition in the behaviour
      and therapeutic response of oral squamous cell carcinoma.
AB  - It is increasingly recognised that phenotypic plasticity, apparently driven by
      epigenetic mechanisms, plays a key role in tumour behaviour and markedly
      influences the important processes of therapeutic survival and metastasis. An
      important source of plasticity in malignancy is epithelial-to-mesenchymal
      transition (EMT), a common epigenetically controlled event that results in
      transition of malignant cells between different phenotypic states that confer
      motility and enhance survival. In this review, we discuss the importance of
      phenotypic plasticity and its contribution to cellular heterogeneity in oral
      squamous cell carcinoma with emphasis on aspects of drug resistance and EMT. 

PMID- 25594910
TI  - Factors impacting parental burden in food-allergic children.
AB  - AIM: This study aims to determine factors impacting the parental burden in
      immunoglobulin E (IgE)-mediated food-allergic children (FAC), focusing on
      attitudes towards adrenaline autoinjectors (AAIs). METHODS: Questionnaires were
      sent to parents of diagnosed IgE-mediated FAC attending follow-up allergy clinic
      appointments at two Sydney hospitals in May-September 2013. The questionnaires
      ascertained parental attitudes, confidence and knowledge regarding AAIs and
      included the validated, Food Allergy Quality of Life-Parental Burden (FAQL-PB)
      questionnaire. RESULTS: The response rate was 68%. Of FAC, 62% were male aged 1
      17 years (median 6.0). There was a high proportion of children with multiple food
      allergies (52% allergic to >2 foods), coexistant eczema (85%) and asthma (54%).
      Sixty-three per cent reported a past history of anaphylaxis and 42% reported
      reactions in the last 6 months. AAI had been prescribed for 84%. FAC with a
      history of anaphylaxis were more likely to have had an AAI prescribed (P <
      0.0001). There was no difference in FAQL-PB mean scores with age or AAI
      prescription status. The PB score was greater if the parent had administered the
      AAI (P = 0.02) and where the child was allergic to >2 foods (P < 0.0001).The
      Ninety per cent of parents reported that the AAI increased or did not change the
      child's quality of life, the family or FACs freedom. Three per cent of parents
      whose FAC children were prescribed an AAI reported increased stress related to
      AAI prescription. CONCLUSION: Severity of food allergy, number of food allergens
      and past anaphylaxis rather than prescription of an AAI appear to be major
      influences on parental burden.

PMID- 25594911
TI  - Hypnosis, hypnotic suggestibility, memory, and involvement in films.
AB  - Our research extends studies that have examined the relation between hypnotic
      suggestibility and experiential involvement and the role of an hypnotic induction
      in enhancing experiential involvement (e.g., absorption) in engaging tasks.
      Researchers have reported increased involvement in reading (Baum & Lynn, 1981)
      and music-listening (Snodgrass & Lynn, 1989) tasks during hypnosis. We predicted
      a similar effect for film viewing: greater experiential involvement in an
      emotional (The Champ) versus a non-emotional (Scenes of Toronto) film. We tested
      121 participants who completed measures of absorption and trait dissociation and
      the Harvard Group Scale of Hypnotic Susceptibility and then viewed the two films
      after either an hypnotic induction or a non-hypnotic task (i.e., anagrams).
      Experiential involvement varied as a function of hypnotic suggestibility and film
      clip. Highly suggestible participants reported more state depersonalization than
      less suggestible participants, and depersonalization was associated with negative
      affect; however, we observed no significant correlation between hypnotic
      suggestibility and trait dissociation. Although hypnosis had no effect on memory
      commission or omission errors, contrary to the hypothesis that hypnosis
      facilitates absorption in emotionally engaging tasks, the emotional film was
      associated with more commission and omission errors compared with the non
      emotional film. 

PMID- 25594912
TI  - Strength training and shoulder proprioception.
AB  - CONTEXT: Proprioception is essential to motor control and joint stability during
      daily and sport activities. Recent studies demonstrated that athletes have better
      joint position sense (JPS) when compared with controls matched for age,
      suggesting that physical training could have an effect on proprioception.
      OBJECTIVE: To evaluate the result of an 8-week strength-training program on
      shoulder JPS and to verify whether using training intensities that are the same
      or divergent for the shoulder's dynamic-stabilizer muscles promote different
      effects on JPS. DESIGN: Randomized controlled clinical trial. SETTING: We
      evaluated JPS in a research laboratory and conducted training in a gymnasium.
      PATIENTS OR OTHER PARTICIPANTS: A total of 90 men, right handed and asymptomatic,
      with no history of any type of injury or shoulder instability. INTERVENTION(S):
      For 8 weeks, the participants performed the strength-training program 3 sessions
      per week. We used 4 exercises (bench press, lat pull down, shoulder press, and
      seated row), with 2 sets each. MAIN OUTCOME MEASURE(S): We measured shoulder JPS
      acuity by calculating the absolute error. RESULTS: We found an interaction
      between group and time. To examine the interaction, we conducted two 1-way
      analyses of variance comparing groups at each time. The groups did not differ at
      pretraining; however, a difference among groups was noted posttraining.
      CONCLUSIONS: Strength training using exercises at the same intensity produced an
      improvement in JPS compared with exercises of varying intensity, suggesting that
      the former resulted in improvements in the sensitivity of muscle spindles and,
      hence, better neuromuscular control in the shoulder.

PMID- 25594913
TI  - Acromiohumeral distance and 3-dimensional scapular position change after overhead
      muscle fatigue.
AB  - CONTEXT: Muscle fatigue due to repetitive and prolonged overhead sports activity
      is considered an important factor contributing to impingement-related rotator
      cuff pathologic conditions in overhead athletes. The evidence on scapular and
      glenohumeral kinematic changes after fatigue is contradicting and prohibits
      conclusions about how shoulder muscle fatigue affects acromiohumeral distance.
      OBJECTIVE: To investigate the effect of a fatigue protocol resembling overhead
      sports activity on acromiohumeral distance and 3-dimensional scapular position in
      overhead athletes. DESIGN: Cross-sectional study. SETTING: Institutional
      laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 29 healthy recreational
      overhead athletes (14 men, 15 women; age = 22.23 +/- 2.82 years, height = 178.3
      +/- 7.8 cm, mass = 71.6 +/- 9.5 kg). INTERVENTION(S): The athletes were tested
      before and after a shoulder muscle-fatiguing protocol. MAIN OUTCOME MEASURE(S):
      Acromiohumeral distance was measured using ultrasound, and scapular position was
      determined with an electromagnetic motion-tracking system. Both measurements were
      performed at 3 elevation positions (0 degrees , 45 degrees , and 60 degrees  of
      abduction). We used a 3-factor mixed model for data analysis. RESULTS: After
      fatigue, the acromiohumeral distance increased when the upper extremity was
      actively positioned at 45 degrees  (Delta = 0.78 +/- 0.24 mm, P = .002) or 60
      degrees  (Delta = 0.58 +/- 0.23 mm, P = .02) of abduction. Scapular position
      changed after fatigue to a more externally rotated position at 45 degrees  (Delta
      = 4.97 degrees  +/- 1.13 degrees , P < .001) and 60 degrees  (Delta = 4.61
      degrees  +/- 1.90 degrees , P = .001) of abduction, a more upwardly rotated
      position at 45 degrees  (Delta = 6.10 degrees  +/- 1.30 degrees , P < .001) and
      60 degrees  (Delta = 7.20 degrees  +/- 1.65 degrees , P < .001) of abduction, and
      a more posteriorly tilted position at 0 degrees , 45 degrees , and 60 degrees  of
      abduction (Delta = 1.98 degrees  +/- 0.41 degrees , P < .001). CONCLUSIONS: After
      a fatiguing protocol, we found changes in acromiohumeral distance and scapular
      position that corresponded with an impingement-sparing situation.

PMID- 25594915
TI  - Avascular necrosis of the metacarpal head: a case of Dietrich's disease and
      review of the literature.
AB  - BACKGROUND: Isolated avascular necrosis of the metacarpal head, also known as
      Dietrich's disease, is a rare entity with few cases reported previously in the
      literature. It has been associated with steroid use, lupus, and trauma. We
      describe the clinical presentation, pathogenesis, and treatment options
      associated with this uncommon condition. CASE REPORT: A 36-year-old man presented
      with a 1-year history of a painful right middle finger metacarpophalangeal joint
      (MCPJ). There was no preceding history of trauma. Routine blood investigations
      and plain-film imaging were unremarkable. Magnetic resonance imaging (MRI)
      revealed a focus of osteonecrosis in the middle finger MCPJ consistent with
      Dietrich's disease. Given the patient's excellent functional status, conservative
      therapy was been successfully undertaken. CONCLUSIONS: Dietrich's disease,
      although a rare entity, must be considered in the differential diagnosis of
      painful MCPJ, where routine blood investigations and plain-film imaging studies
      are unremarkable.

PMID- 25594914
TI  - What can the first 2 months tell us about outcomes after anterior cruciate
      ligament reconstruction?
AB  - CONTEXT: Substantial research has been conducted on anterior cruciate ligament
      reconstruction (ACLR) to evaluate patient outcomes. However, little attention has
      been given to outcomes during the early phase of recovery and how early deficits
      affect both short- and long-term outcomes. OBJECTIVE: To identify relationships
      between demographic (age, sex, and body mass index [BMI]) and intraoperative
      (isolated ACLR versus primary ACLR + secondary procedures), and postoperative
      (range-of-motion [ROM] and peak isometric knee-extension force [PIF]) variables
      during the first 2 months after ACLR using self-reported outcomes. DESIGN: Cohort
      study. SETTING: Outpatient orthopaedic hospital. PATIENTS OR OTHER PARTICIPANTS:
      A total of 63 patients (38 men, 25 women; age = 33.0 +/- 12.1 years; BMI = 26.3
      +/- 6.5 kg/m(2)) who underwent ACLR. MAIN OUTCOME MEASURE(S): Demographic,
      intraoperative, and postoperative variables were collected at 1 and 2 months
      after ACLR and were compared with International Knee Documentation Committee
      (IKDC) Subjective Knee Evaluation Form scores at 1, 2, and >=12 months. RESULTS:
      Significant relationships were identified between >=12-month IKDC scores and the
      1-month (Pearson correlation, r = 0.283, r(2) = 0.08; P = .025) and 2-month (r =
      0.301, r(2) = 0.09; P = .017) IKDC scores. After controlling for other variables,
      we found that the PIF ratio measures at 1 and 2 months were positively associated
      with 1- and 2-month IKDC scores (P < .001) and BMI was negatively associated with
      both 1- and 2-month IKDC scores (P < .05). One-month IKDC scores were related to
      the 1-month difference in knee-flexion ROM (P = .04). CONCLUSIONS: The IKDC
      scores during the first 2 months were positively correlated with patients'
      perceptions of function on long-term IKDC scores. It also appears that
      improvements in lower extremity strength and flexion ROM deficits were positively
      associated with short-term IKDC scores. Higher BMI was negatively associated with
      patients' perceptions of function on short-term IKDC scores.

PMID- 25594916
TI  - Multi stimuli-responsive hydrogel microfibers containing magnetite nanoparticles
      prepared using microcapillary devices.
AB  - Extensive research efforts have been devoted to the development of hydrogel
      microfibers for tissue engineering, because the vascular structure is related to
      the transport of nutrients and oxygen as well as the control of metabolic and
      mechanical functions in the human body. Even though stimuli-responsive properties
      would enhance the potential applicability of hydrogel microfibers for artificial
      tissue architectures, previous studies of their fabrication have not considered
      changes in the microfibers in response to external stimuli. In this work, we
      prepared temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) microfibers
      with controlled shapes and sizes by the in situ photo-polymerization of aqueous
      monomers loaded in calcium alginate templates generated from microcapillary
      devices. We found that the shape and size of the hydrogel microfibers could be
      controlled by adjusting the injection positions of the solutions and varying the
      diameters of the inner capillary, respectively. We further fabricated light
      responsive materials by incorporating photothermal magnetite nanoparticles (MNPs)
      within the temperature-responsive PNIPAm hydrogel microfibers. Because the MNPs
      incorporated into the PNIPAm microfibers generated heat upon the absorption of
      visible light, we could demonstrate volume changes in the microfibers triggered
      by both visible light irradiation and temperature. 

PMID- 25594917
TI  - The process, outcomes, and challenges of feasibility studies conducted in
      partnership with stakeholders: a health intervention for women survivors of
      intimate partner violence.
AB  - Feasibility studies play a crucial role in determining whether complex, community
      based interventions should be subject to efficacy testing. Reports of such
      studies often focus on efficacy potential but less often examine other elements
      of feasibility, such as acceptance by clients and professionals, practicality,
      and system integration, which are critical to decisions for proceeding with
      controlled efficacy testing. Although stakeholder partnership in feasibility
      studies is widely suggested to facilitate the research process, strengthen
      relevance, and increase knowledge transfer, little is written about how this
      occurs or its consequences and outcomes. We began to address these gaps in
      knowledge in a feasibility study of a health intervention for women survivors of
      intimate partner violence (IPV) conducted in partnership with policy, community
      and practitioner stakeholders. We employed a mixed-method design, combining a
      single-group, pre-post intervention study with 52 survivors of IPV, of whom 42
      completed data collection, with chart review data and interviews of 18
      purposefully sampled participants and all 9 interventionists. We assessed
      intervention feasibility in terms of acceptability, demand, practicality,
      implementation, adaptation, integration, and efficacy potential. Our findings
      demonstrate the scope of knowledge attainable when diverse elements of
      feasibility are considered, as well as the benefits and challenges of
      partnership. The implications of diverse perspectives on knowledge transfer are
      discussed. Our findings show the importance of examining elements of feasibility
      for complex community-based health interventions as a basis for determining
      whether controlled intervention efficacy testing is justified and for refining
      both the intervention and the research design.

PMID- 25594918
TI  - Clinical proteomics: promises, challenges and limitations of affinity arrays.
AB  - After the establishment of DNA/RNA sequencing as a means of clinical diagnosis,
      the analysis of the proteome is next in line. As a matter of fact, proteome-based
      diagnostics is bound to be even more informative, since proteins are directly
      involved in the actual cellular processes that are responsible for disease.
      However, the structural variation and the biochemical differences between
      proteins, the much wider range in concentration and their spatial distribution as
      well as the fact that protein activity frequently relies on interaction increase
      the methodological complexity enormously, particularly if an accuracy and
      robustness is required that is sufficient for clinical utility. Here, we discuss
      the contribution that protein microarray formats could play towards proteome
      based diagnostics.

PMID- 25594919
TI  - Cost-effectiveness analysis of adding pharmacists to primary care teams to reduce
      cardiovascular risk in patients with Type 2 diabetes: results from a randomized
      controlled trial.
AB  - BACKGROUND: Adding pharmacists to primary care teams significantly improved blood
      pressure control and reduced predicted 10-year cardiovascular risk in patients
      with Type 2 diabetes. This pre-specified sub-study evaluated the economic
      implications of this cardiovascular risk reduction strategy. METHODS: One-year
      outcomes and healthcare utilization data from the trial were used to determine
      cost-effectiveness from the public payer perspective. Costs were expressed in
      2014 Canadian dollars and effectiveness was based on annualized risk of
      cardiovascular events derived from the UKPDS Risk Engine. RESULTS: The 123
      evaluable trial patients included in this analysis had a mean age of 62 ( +/- 11)
      years, 38% were men, and mean diabetes duration was 6 ( +/- 7) years. Pharmacists
      provided 3.0 ( +/- 1.9) hours of additional service to each intervention patient,
      which cost $226 ( +/- $1143) per patient. The overall one-year per-patient costs
      for healthcare utilization were $190 lower in the intervention group compared
      with usual care [95% confidence interval (CI): -$1040, $668). Intervention
      patients had a significant 0.3% greater reduction in the annualized risk of a
      cardiovascular event (95% CI: 0.08%, 0.6%) compared with usual care. In the cost
      effectiveness analysis, the intervention dominated usual care in 66% of 10,000
      bootstrap replications. At a societal willingness-to-pay of $4000 per 1%
      reduction in annual cardiovascular risk, the probability that the intervention
      was cost-effective compared with usual care reached 95%. A sensitivity analysis
      using multiple imputation to replace missing data produced similar results.
      CONCLUSIONS: Within a randomized trial, adding pharmacists to primary care teams
      was a cost-effective strategy for reducing cardiovascular risk in patients with
      Type 2 diabetes. In most circumstances, this intervention may also be cost
      saving.

PMID- 25594920
TI  - Microvessel density in hepatocellular carcinoma: Prognostic significance and
      review of the previous published work.
AB  - AIM: Assessment of the microvessel density (MVD) may yield important information
      leading to an effective antiangiogenic treatment for hepatocellular carcinoma
      (HCC). METHODS: The intratumoral MVD of 136 HCC patients was retrospectively
      evaluated using CD34. The correlation between the MVD and clinicopathological
      findings was assessed. In addition, the prognostic factors influencing the 2-year
      disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The
      MVD of each tumor size group (<2, 2-5 and >5 cm) was 196 +/- 51, 181 +/- 63 and
      147 +/- 69. The MVD of each histological grade (well-, moderately and poorly
      differentiated) was 200 +/- 56, 184 +/- 61 and 114 +/- 55. The optimum cut-off
      values of the MVD for the 2-year DFS and OS were 118.3 and 112.7, respectively.
      For the 2-year DFS, high tumor marker levels (alpha-fetoprotein >100 ng/mL and
      protein induced by vitamin K absence/antagonist-II >100 mAU/mL), poorly
      differentiated hepatocellular carcinoma (HCC), a high Ki-67 index (>20%), a large
      tumor size (>5 cm), vascular invasion, high tumor-node-metastasis (TNM) stage
      (III/IV) and a low MVD were the significant unfavorable prognostic factors. For
      the OS, a high Ki-67 index, a large tumor size, vascular invasion, high TNM stage
      and a low MVD were the significant risk factors for death. By the multivariate
      analysis, a low MVD was identified as an independent predictor of the 2-year DFS
      as well as the OS. CONCLUSION: A low MVD can be used to predict an unfavorable
      prognosis in HCC patients.

PMID- 25594921
TI  - 'From Man to Bacteria': W.D. Hamilton, the theory of inclusive fitness, and the
      post-war social order.
AB  - W.D. Hamilton's theory of inclusive fitness aimed to define the evolved limits of
      altruism with mathematical precision. Although it was meant to apply universally,
      it has been almost irretrievably entwined with the particular case of social
      insects that featured in his famous 1964 papers. The assumption that social
      insects were central to Hamilton's early work contradicts material in his rich
      personal archive. In fact, careful study of Hamilton's notes, letters, diaries,
      and early essays indicates the extent to which he had humans in mind when he
      decided altruism was a topic worthy of biological inquiry. For this reason, this
      article reconsiders the role of extra-scientific factors in Hamilton's early
      theorizing. In doing so, it offers an alternative perspective as to why Hamilton
      saw self-sacrifice to be an important subject. Although the traditional narrative
      prioritizes his distaste for benefit-of-the-species explanations as a motivating
      factor behind his foundational work, I argue that greater attention ought to be
      given to Hamilton's hope that science could be used to address social ills. By
      reconsidering the meaning Hamilton intended inclusive fitness to have, we see
      that while he was no political ideologue, the socio-political relevance of his
      theory was nevertheless integral to its development. 

PMID- 25594922
TI  - Paraconfuranones A-H, eight new furanone analogs from the insect-associated
      fungus Paraconiothyrium brasiliense MZ-1.

PMID- 25594923
TI  - Letter by Bassareo regarding the article of Larrson et al. "incidence of atrial
      fibrillation in relation to birth weight and preterm birth".

PMID- 25594924
TI  - Fatal prosthetic mitral valve encroachment during transcatheter aortic valve
      implantation.

PMID- 25594925
TI  - Quantification of diastolic dysfunction via the age dependence of diastolic
      function - impact of insulin resistance with and without type 2 diabetes.
AB  - BACKGROUND: The alarming prevalence of heart failure with preserved ejection
      fraction requires quantification of diastolic dysfunction (DDF). Myocardial
      diastolic velocity E' implies that age is the most important determinant. We
      tested the hypothesis that age allows for quantification of DDF and assessment of
      the structural and metabolic determinants in patients with and without type 2
      diabetes (D). METHODS: This prospective, cross-sectional study assessed
      cardiovascular, metabolic and ultrasound data in 409 consecutive patients
      (Diabetes Center, Bogenhausen-Munich) between 20 and 90 years without known
      cardiac disease and either with (n=204) or without D but with common prevalence
      of cardiovascular risk factors, including a subgroup of healthy individuals (H,
      n=94). RESULTS: In H, E' related to age as: E'norm=-0.163*years+19.69 (R(2)=0.77,
      p<0.0001). According to this 1% reduction by annual physiologic aging, DDF was
      quantitated as E'-E' norm. Compared to nondiabetics, D patients were older, had
      greater BMI, lower E', more cardiovascular risk and greater DDF. In nondiabetics,
      grading of DDF by E-E'norm correlated with grading by filling pressure E/E'.
      Determinants of DDF by multivariate analysis included pulse wave velocity,
      diastolic blood pressure and the triglyceride/HDL ratio (a marker of insulin
      resistance) in nondiabetics and in D the same risk factors in reverse sequence
      and heart rate. Neither left atrial size nor left ventricular mass had
      significant impact. CONCLUSIONS: The physiological impact of age on myocardial
      function consists of a 1% annual reduction in E' and enables precise
      quantification of diastolic dysfunction thereby unmasking the importance of
      metabolic risk for DDF.

PMID- 25594926
TI  - The association between components of height and blood pressure among children
      and adolescents in Shandong, China.

PMID- 25594927
TI  - A patient with recurrent disabling atrial fibrillation and Fabry cardiomyopathy
      successfully treated with single ring pulmonary vein isolation.

PMID- 25594928
TI  - Giant biventricular thrombi in a patient with heart failure and heparin-induced
      thrombocytopenia.

PMID- 25594929
TI  - Life-threatening complete atrioventricular block associated with ticagrelor
      therapy.

PMID- 25594930
TI  - Takotsubo cardiomyopathy, beyond ventriculography and classical bidimensional
      echocardiography.

PMID- 25594931
TI  - Giant saphenous vein graft aneurysm: a complex multi-disciplinary percutaneous
      approach.

PMID- 25594932
TI  - Effort-reward imbalance at work increases the risk of the metabolic syndrome: a
      prospective study in Chinese university staff.

PMID- 25594933
TI  - Artificial photosynthesis for sustainable fuel and chemical production.
AB  - The apparent incongruity between the increasing consumption of fuels and
      chemicals and the finite amount of resources has led us to seek means to maintain
      the sustainability of our society. Artificial photosynthesis, which utilizes
      sunlight to create high-value chemicals from abundant resources, is considered as
      the most promising and viable method. This Minireview describes the progress and
      challenges in the field of artificial photosynthesis in terms of its key
      components: developments in photoelectrochemical water splitting and recent
      progress in electrochemical CO2 reduction. Advances in catalysis, concerning the
      use of renewable hydrogen as a feedstock for major chemical production, are
      outlined to shed light on the ultimate role of artificial photosynthesis in
      achieving sustainable chemistry. 

PMID- 25594934
TI  - The cost of lost productivity due to fetal alcohol spectrum disorder-related
      premature mortality.
AB  - BACKGROUND: Individuals with Fetal Alcohol Spectrum Disorder (FASD) have
      increased mortality as compared to the general population. OBJECTIVES: To
      estimate the productivity losses due to premature mortality of individuals with
      FASD in Canada in 2011. METHODS: A demographic approach with a counterfactual
      scenario in which nobody in Canada is born with FASD was used. Population
      estimates were calculated using data on the labour force, unemployment rate, and
      average weekly wage obtained from Statistics Canada. The number of FASD-related
      deaths, coded in the International Classification of Diseases, version 10, was
      estimated based on data from Statistics Canada and pooled prevalence estimates of
      the major disease conditions associated with FASD were obtained from a meta
      analysis. The estimates of FASD-related mortality rates served as a basis for the
      length of working life span estimation. Once the number of working years lost to
      premature deaths was derived, productivity losses were computed. RESULTS: It was
      estimated that in total 327 individuals with FASD aged 20 to 69 (almost twice as
      many men as women) died in Canada in 2011. As a result, there were 2,877 years of
      potential employment lost, which translated to a loss ranging from $88 million to
      $126 million. This amount represents the increase in national income, had there
      been no premature mortality from FASD and the workers with FASD had been typical
      members of the labour force (without compromised productivity due to FASD).
      CONCLUSIONS: The estimates of productivity losses further reinforce the value of
      FASD prevention as a primary strategy.

PMID- 25594935
TI  - Activated carbons impregnated with iron oxide nanoparticles for enhanced removal
      of bisphenol A and natural organic matter.
AB  - The removal of bisphenol A (BPA) is important for the provision of safe drinking
      water, but its removal in the presence of natural organic matter (NOM) is
      challenging. Thus, the present study involved the fabrication and
      characterization of powdered activated carbons impregnated with iron oxide
      nanoparticles (IONPACs) with respect to the simultaneous removal of BPA and NOM.
      The number of Fe ions loaded into the PAC pores was optimized in terms of
      exposure time. Impregnation with iron oxide reduced the surface area and pore
      volume, but the pore size was maintained. IONPAC adsorbents had considerably
      greater sorption capabilities for BPA and NOM compared to native, bare PAC
      particles. The adsorption capacities of BPA and NOM were in the following
      sequence: bare PAC<hematite/PAC < magnetite/PAC < ferrihydrite/PAC. The enhanced
      removal by IONPACs was attributable to the surface coordination between the
      functional groups in the iron oxides (e.g., hydroxyl groups) and organics (e.g.,
      phenolic/carboxyl groups). Iron oxide impregnation enabled the BPA uptake to be
      maintained in the presence of NOM, indicating that the hybrid adsorbent provided
      synergistic adsorption characteristics for BPA and NOM. Although the solution pH
      had a negligible impact on BPA uptake, the ionic strength showed a significant
      effect, particularly in the presence of divalent Ca ions.

PMID- 25594936
TI  - Lanthanum rather than cadmium induces oxidative stress and metabolite changes in
      Hypericum perforatum.
AB  - Physiology, oxidative stress and production of metabolites in Hypericum
      perforatum exposed to moderate Cd and/or La concentration (10 MUM) were studied.
      La evoked increase in reactive oxygen species, malondialdehyde and proline but
      suppressed growth, tissue water content, glutathione, ascorbic acid and affected
      mineral nutrient contents more than Cd while the impact of Cd+La was not
      synergistic. Similar trend was observed at the level of superoxide dismutase gene
      expression. Shoot Cd amount increased in Cd+La while only root La increased in
      the same treatment. Extensive quantification of secondary metabolites revealed
      that La affected phenolic acids more pronouncedly than Cd in shoots and roots.
      Flavonols were suppressed by La that could contribute to the appearance of
      oxidative damage. Procyanidins increased in response to La in the shoots but
      decreased in the roots. Metabolic responses in Cd+La treatment resembled those of
      La treatment (almost identically in the roots). Phenylalanine ammonia-lyase
      activity was mainly suppressed by La. The presence of La also depleted amount of
      hypericin and expression of its putative gene (hyp-1) showed similar trend but
      accumulation of hyperforin increased under Cd or La excess. Clear differences in
      the stem and root anatomy in response to Cd or La were also found. Overall, H.
      perforatum is La-sensitive species and rather Cd ameliorated negative impact of
      La.

PMID- 25594937
TI  - Motor activity in young APPswe  + PS1/A246E bigenic mice as a predicting variable
      for memory decline.
AB  - Reports of individuality in rodent species have been a subject of debate in
      pharmacology and other fields. In the current study, APPswe  + PS1/A246E bigenic
      mice with Alzheimer's-like pathogenesis and wild-type controls were subdivided at
      3 months of age into low, intermediate, and high responders in open-field
      activity. The mice were then evaluated longitudinally at 3 and 9 months for
      object recognition. Irrespective of genotype, mice with a high level of motor
      activity had better scores in object recognition. However, a significant
      correlation was established between open-field activity measured at 3 months of
      age and recognition memory measured at 9 months of age in the bigenic group only.
      These results indicate that motor activity in young mice with amyloid
      neuropathology may serve as a predicting variable for cognitive dysfunction in
      more mature mice.

PMID- 25594938
TI  - Evolutionary factors affecting the cross-species utility of newly developed
      microsatellite markers in seabirds.
AB  - Microsatellite loci are ideal for testing hypotheses relating to genetic
      segregation at fine spatio-temporal scales. They are also conserved among closely
      related species, making them potentially useful for clarifying interspecific
      relationships between recently diverged taxa. However, mutations at primer
      binding sites may lead to increased nonamplification, or disruptions that may
      result in decreased polymorphism in nontarget species. Furthermore, high mutation
      rates and constraints on allele size may also with evolutionary time, promote an
      increase in convergently evolved allele size classes, biasing measures of
      interspecific genetic differentiation. Here, we used next-generation sequencing
      to develop microsatellite markers from a shotgun genome sequence of the sub
      Antarctic seabird, the thin-billed prion (Pachyptila belcheri), that we tested
      for cross-species amplification in other Pachyptila and related sub-Antarctic
      species. We found that heterozygosity decreased and the proportion of
      nonamplifying loci increased with phylogenetic distance from the target species.
      Surprisingly, we found that species trees estimated from interspecific FST
      provided better approximations of mtDNA relationships among the studied species
      than those estimated using DC , even though FST was more affected by null
      alleles. We observed a significantly nonlinear second order polynomial
      relationship between microsatellite and mtDNA distances. We propose that the loss
      of linearity with increasing mtDNA distance stems from an increasing proportion
      of homoplastic allele size classes that are identical in state, but not identical
      by descent. Therefore, despite high cross-species amplification success and high
      polymorphism among the closely related Pachyptila species, we caution against the
      use of microsatellites in phylogenetic inference among distantly related taxa. 

PMID- 25594939
TI  - Specific absorption rate in neonates undergoing magnetic resonance procedures at
      1.5 T and 3 T.
AB  - MRI is finding increased clinical use in neonatal populations; the extent to
      which electromagnetic models used for quantification of specific absorption rate
      (SAR) by commercial MRI scanners accurately reflect this alternative scenario is
      unclear. This study investigates how SAR predictions relating to adults can be
      related to neonates under differing conditions when imaged using 1.5 T and 3 T
      MRI scanners. Electromagnetic simulations were produced in neonatal subjects of
      different sizes and positions within a generic MRI body transmit device operating
      at both 64 MHz and 128 MHz, corresponding to 1.5 T and 3 T MRI scanners,
      respectively. An adult model was also simulated, as was a spherical salt-water
      phantom, which was also used in a calorimetry experiment. The SAR in neonatal
      subjects was found to be less than that experienced in an adult in all scenarios;
      however, the overestimation factor was variable. For example a 3 T body scan
      resulting in local 10 g SAR of 10.1 W kg(-1) in an adult would deposit 2.6 W kg(
      1) in a neonate: an approximately fourfold difference. The SAR experienced by
      neonatal subjects undergoing MRI is lower than that in adults in equivalent
      situations. If the safety of such procedures is assessed using adult-appropriate
      models then the result is a conservative estimate.

PMID- 25594940
TI  - Validation of a novel attentional bias modification task: the future may be in
      the cards.
AB  - Attentional bias modification (ABM) is a promising therapeutic tool aimed at
      changing patterns of attentional selectivity associated with heightened anxiety.
      A number of studies have successfully implemented ABM using the modified dot
      probe task. However others have not achieved the attentional change required to
      achieve emotional benefits, highlighting the need for new ABM methods. The
      current study compared the effectiveness of a newly developed ABM task against
      the traditional dot-probe ABM task. The new person-identity-matching (PIM) task
      presented participants with virtual cards, each depicting a happy and angry
      person. The task encourages selective attention toward or away from threat by
      requiring participants to make matching judgements between two cards, based
      either on the identities of the happy faces, or of the angry faces. Change in
      attentional bias achieved by both ABM tasks was measured by a dot-probe
      assessment task. Their impact on emotional vulnerability was assessed by
      measuring negative emotional reactions to a video stressor. The PIM task
      succeeded in modifying attentional bias, and exerting an impact on emotional
      reactivity, whereas this was not the case for the dot-probe task. These results
      are considered in relation to the potential clinical utility of the current task
      in comparison to traditional ABM methodologies. 

PMID- 25594942
TI  - Critical appraisal of clinical practice guidelines for treating pancreatic cancer
      based on the global disease burden.
AB  - OBJECTIVES: To evaluate the quality of pancreatic cancer guidelines with evidence
      based methods based on the global burden of disease and to explore its status,
      distribution, characteristics of theme, and the difference of recommended
      therapies among various qualities of guidelines, so as to provide a reference for
      clinical decision. METHODS: The PubMed, The Cochrane Library (Issue 11, 2013),
      Chinese Biomedical Database, China National Knowledge Infrastructure, and VIP
      databases, as well as the website of National Guidelines Clearinghouse,
      Guidelines International Network, and National Institute for Clinical Excellence
      were systematically reviewed through November 2013 for pancreatic cancer
      guidelines. The Appraisal of Guidelines for Research and Evaluation (AGREE II)
      were applied to assess the methodological quality of the guidelines. RESULTS: A
      total of 14 relevant guidelines (including 5 evidence-based ones) were
      identified, involving four continents (Asia, Europe, North America, and Oceania),
      seven counties, and four international organizations. There were only two
      domains, namely 'scope and purpose' and 'clarity of presentations', getting high
      average scores (more than 60%) among all 14 guidelines. The mean AGREE domain
      score in guidelines varies among different areas, and the quality of 5 evidence
      based guidelines was superior to that established by consensus. According to
      AGREE II, 11 guidelines were weakly recommended, while 3 were not recommended due
      to poor methodological quality. Their subjects of 14 guidelines covered six
      treatment categories, including chemotherapy, surgery, radiotherapy, support
      therapy, radiotherapy, and interventional therapy. CONCLUSION: The overall
      methodological quality of pancreatic cancer guidelines is suboptimal among
      different countries or regions. The qualities of evidence-based guidelines are
      significantly superior to consensus. The chemotherapy, surgery, radiotherapy, and
      support therapy were the predominant choices by guidelines.

PMID- 25594941
TI  - Warfarin dosage response related pharmacogenetics in Chinese population.
AB  - OBJECTIVES: As the most frequently prescribed anticoagulant, warfarin has large
      inter-individual variability in dosage. Genetic polymorphisms could largely
      explain the differences in dosage requirement. rs9923231 (VKORC1), rs7294
      (VKORC1), rs1057910 (CYP2C9), rs2108622 (CYP4F2), and rs699664 (GGCX) involved in
      the warfarin action mechanism and the circulatory vitamin K were selected to
      investigate their polymorphism characteristics and their effects on the
      pharmacodynamics and pharmacokinetics of warfarin in Chinese population. METHODS:
      220 patients with cardiac valve replacement were recruited. International
      normalized ratio and plasma warfarin concentrations were determined. The five
      genetic polymorphisms were genotyping by pyro-sequencing. The relationships of
      maintenance dose, plasma warfarin concentration and INR were assessed among
      groups categorized by genotypes. RESULTS: rs9923231 and rs7294 in VKORC1 had the
      analogous genotype frequencies (D': 0.969). 158 of 220 recruited individuals had
      the target INR (1.5-2.5). Patients with AA of rs9923231 and CC of rs7294 required
      a significantly lower maintenance dose and plasma concentration than those with
      AG and TC, respectively. The mean weekly maintenance dose was also significantly
      lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild
      homozygote. Eliminating the influence from environment factors (age, body weight
      and gender), rs9923231 and rs1057910 could explain about 32.0% of the variability
      in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in
      plasma concentration. For patients with allele G of rs9923231 and allele T of
      rs7294, higher plasma concentration was needed to achieve the similar goal INR.
      CONCLUSIONS: A better understanding of the genetic variants in individuals can be
      the foundation of warfarin dosing algorithm and facilitate the reasonable and
      effective use of warfarin in Chinese.

PMID- 25594944
TI  - The team physician and strength and conditioning of athletes for sports: a
      consensus statement.

PMID- 25594943
TI  - Anticancer and anti-inflammatory properties of chitin and chitosan
      oligosaccharides.
AB  - Previous reports indicate that N-acetyl-d-glucosamine oligomers (chitin
      oligosaccharide; NACOS) and d-glucosamine oligomers (chitosan oligosaccharide;
      COS) have various biological activities, especially against cancer and
      inflammation. In this review, we have summarized the findings of previous
      investigations that have focused on anticancer or anti-inflammatory properties of
      NACOS and COS. Moreover, we have introduced recent evaluation of NACOS and COS as
      functional foods against cancer and inflammatory disease. 

PMID- 25594945
TI  - Eccentric loading and upper limb muscle-bone asymmetries in elite tennis players.

PMID- 25594946
TI  - The impact of signal-to-noise ratio on contextual cueing in children and adults.
AB  - Contextual cueing refers to a form of implicit spatial learning where
      participants incidentally learn to associate a target location with its repeated
      spatial context. Successful contextual learning produces an efficient visual
      search through familiar environments. Despite the fact that children exhibit the
      basic ability of implicit spatial learning, their general effectiveness in this
      form of learning can be compromised by other development-dependent factors.
      Learning to extract useful information (signal) in the presence of various
      amounts of irrelevant or distracting information (noise) characterizes one of the
      most important changes that occur with cognitive development. This research
      investigated whether signal-to-noise ratio (S/N) affects contextual cueing
      differently in children and adults. S/N was operationally defined as the ratio of
      repeated versus new displays encountered over time. Three ratio conditions were
      created: high (100%), medium (67%), and low (33%) conditions. Results suggested
      no difference in the acquisition of contextual learning effects in the high and
      medium conditions across three age groups (6- to 8-year-olds, 10- to 12-year
      olds, and young adults). However, a significant developmental difference emerged
      in the low S/N condition. As predicted, adults exhibited significant contextual
      cueing effects, whereas older children showed marginally significant contextual
      cueing and younger children did not show cueing effects. Group differences in the
      ability to exhibit implicit contextual learning under low S/N conditions and the
      implications of this difference are discussed. 

PMID- 25594947
TI  - pH-metric chemical speciation modeling and studies of in vitro antidiabetic
      effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes.
AB  - A range of bidentate N,O-donor ligands of the imidazolyl-carboxylate moiety,
      which partially mimic naturally occurring bioligands, were prepared and reacted
      with the oxidovanadium(IV) ion to form the corresponding bis-coordinated
      oxidovanadium(IV) complexes. The aqueous pH-metric chemical speciation was
      investigated using glass electrode potentiometry, which allowed for the
      determination of protonation and stability constants of the ligands and
      complexes, respectively. The species distribution diagrams generated from this
      information gave evidence that the bis[(imidazolyl)carboxylato]oxovanadium(IV)
      complexes possess a broad pH-metric stability. The complexes improved glucose
      uptake in cell cultures using 3T3-L1 adipocytes, C2C12 muscle cells and Chang
      liver cells. The PTP inhibition studies indicated that the mechanism underlying
      insulin-stimulated glucose uptake was possibly via the protein tyrosine
      phosphorylation through the inhibition of the protein tyrosine phosphatase 1B
      (PTP 1B). The vanadium compounds also demonstrated the inhibition of D-dimer
      formation, suggesting that these compounds could potentially relieve a
      hypercoagulative state in diabetic patients. 

PMID- 25594948
TI  - Regulation of keratin network organization.
AB  - Keratins form the major intermediate filament cytoskeleton of epithelia and are
      assembled from heterodimers of 28 type I and 26 type II keratins in cell- and
      differentiation-dependent patterns. By virtue of their primary sequence
      composition, interactions with cell adhesion complexes and components of major
      signaling cascades, keratins act as targets and effectors of mechanical force and
      chemical signals to determine cell mechanics, epithelial cohesion and modulate
      signaling in keratin isotype-specific manners. Therefore, cell-specific keratin
      expression and organization impact on cell growth, migration and invasion. Here,
      we review the recent literature, focusing on the question how keratin networks
      are regulated and how the interplay of keratins with adhesion complexes affects
      these processes and provides a framework to understand keratins contribution to
      blistering and inflammatory disorders and to tumor metastasis. 

PMID- 25594949
TI  - Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in
      healthy cats.
AB  - Exenatide extended-release (ER) is a microencapsulated formulation of the
      glucagon-like peptide 1-receptor agonist exenatide. It has a protracted
      pharmacokinetic profile that allows a once-weekly injection with comparable
      efficacy to insulin with an improved safety profile in type II diabetic people.
      Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single
      subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0.
      Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target =
      225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements
      of insulin and glucagon concentrations. Glucose tolerance was defined as the
      amount of glucose required to maintain hyperglycemia during the clamp. Continuous
      glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma
      concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing
      clamp I with clamp II, fasting blood glucose decreased (mean +/- standard
      deviation = -11 +/- 8 mg/dL, P = 0.02), glucose tolerance improved (median
      [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [
      9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%
      12.1%], P = 0.005). Compared with preinjection values on continuous glucose
      monitoring, glucose concentrations decreased and the frequency of readings <50
      mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not
      correspond to clinical hypoglycemia. No other side effects were observed
      throughout the study. Exenatide ER was safe and effective in improving glucose
      tolerance 3 wk after a single injection. Further evaluation is needed to
      determine its safety, efficacy, and duration of action in diabetic cats.

PMID- 25594951
TI  - Determination of ultra-trace organic acids in Masson pine (Pinus massoniana L.)
      by accelerated solvent extraction and liquid chromatography-tandem mass
      spectrometry.
AB  - An accelerated solvent extraction (ASE)-solid-phase extraction (SPE)-liquid
      chromatography with electrospray ionization-tandem mass spectrometry (ASE-SPE-LC
      ESI-MS/MS) methodology was developed for the extraction, cleanup and
      quantification of ultra-trace organic acids in Masson pine (Pinus massoniana L.)
      tissues. The separation was carried out on a Bio-Rad Aminex HPX-87H sulfonic
      column with an eluent containing 5 mmol L(-1) H2SO4 at a flow rate of 0.5 mL min(
      1). A linear ion trap mass spectrometer equipped with electrospray ionization
      (ESI) source was operated in negative ion mode, and the six organic acids were
      eluted within 20 min. ASE extraction, SPE cleanup and LC-ESI-MS/MS analysis
      conditions were optimized to obtain reliable information about plant organic acid
      composition. Selective reaction monitoring (SRM) was employed for quantitative
      measurement. Intra-day precisions averaged 6.7%, and inter-day precisions were
      2.1-10.7% for organic acid measurements in the pine samples. External standard
      calibration curves were linear over the range of 16.5-5000 ng L(-1), and
      detection limits based on a signal-to-noise ratio of three were at 0.5-5.0 ng L(
      1). The results obtained showed the sensibility of the method was better than
      that of previously described HPLC methodology, and had no significant matrix
      effect. The proposed ASE-SPE-LC-ESI-MS/MS method is sensitive and reliable for
      the determination of ultra-trace organic acids in plant samples, despite the
      presence of the particularly complex matrix.

PMID- 25594950
TI  - Regulation of lipid metabolism and peroxisome proliferator-activated receptors in
      rainbow trout adipose tissue by lipolytic and antilipolytic endocrine factors.
AB  - The aim of this study was to determine the effects of growth hormone (GH) and
      insulin-like growth factor (IGF)-I on glycerol release and the regulation of IGF
      I and IGF-II expression by GH in isolated rainbow trout adipocytes. Cells were
      also incubated with GH, tumor necrosis factor alpha (TNFalpha), or insulin to
      analyze the gene expression of peroxisome proliferator-activated receptors
      (PPARs) and lipid metabolism markers: hormone sensitive lipase, fatty acid
      synthase (FAS), and lipoprotein lipase. Complimentary in vivo experiments were
      performed by intraperitoneally administering insulin, TNFalpha, or
      lipopolysaccharide and subjecting the animals to fasting and refeeding periods.
      The results showed that IGF-I had an antilipolytic effect and GH had a lipolytic
      effect; the latter occurred independently of IGF modulation and in conjunction
      with a reduction in PPARalpha expression in adipocytes. The anabolic action of
      insulin was demonstrated through its upregulation of lipogenic genes such as
      lipoprotein lipase, FAS, and PPARgamma, whereas GH, by contrast, inhibited FAS
      expression in adipose tissue. The gene transcription levels of PPARs changed
      differentially during fasting and refeeding, and the TNFalpha and/or
      lipopolysaccharide administration suggested that the regulation of PPARs helps
      maintain metabolic adipose tissue homeostasis in rainbow trout.

PMID- 25594952
TI  - Pharmacokinetics of Rac inhibitor EHop-016 in mice by ultra-performance liquid
      chromatography tandem mass spectrometry.
AB  - The Rho GTPase Rac is an important regulator of cancer cell migration and
      invasion; processes required for metastatic progression. We previously
      characterized the small molecule EHop-016 as a novel Rac inhibitor in metastatic
      breast cancer cells and recently found that EHop-016 was effective at reducing
      tumor growth in nude mice at 25 mg/kg bodyweight (BW). The purpose of this study
      was to compare the pharmacokinetics and bioavailability of EHop-016 at different
      dosages in a single dose input scheme (10, 20 and 40 mg/kg BW) following
      intraperitoneal (IP) and oral gavage (PO) administration to nude mice. We
      developed and validated a rapid and sensitive method for the quantitation of EHop
      016 in mouse plasma by ultra high performance liquid chromatography coupled with
      electrospray ionization tandem mass spectrometry (UPLC/MS/MS). Separation was
      carried out on an Agilent Poroshell 120 EC-C18 column (3.0 mm * 50 mm) using
      organic and aqueous mobile phases. EHop-016 was identified from its accurate mass
      and retention time from the acquired full-scan chromatogram and quantified by its
      peak area. The validated method was linear (R(2)>0.995) over the range of 5-1000
      ng/mL (1/x(2) weighting). Pharmacokinetic parameters were obtained by non
      compartmental analysis using WinNonlin. The area under the curve (AUC0-infinity)
      ranged from 328 to 1869 ng h/mL and 133-487 ng h/mL for IP and PO dosing,
      respectively. The elimination half-life (t1/2) ranged from 3.8-5.7 h to 3.4-26.8
      h for IP and PO dosing, respectively. For both IP and PO administration, the AUC0
      infinityvalues were proportional to the tested doses demonstrating linear PK
      profiles. The relative bioavailability of EHop-016 after oral gavage
      administration ranged from 26% to 40%. These results support further preclinical
      evaluation of EHop-016 as a new anti-cancer therapy.

PMID- 25594953
TI  - The roles of culture and gender in the relationship between divorce and suicide
      risk: a meta-analysis.
AB  - With some exceptions, literature has consistently shown that divorced populations
      are at higher risk for suicide than married ones. Here we make use of
      coefficients of aggravation (COAs), suicide rate ratios of the divorcees over the
      married, to study patterns of COAs and test the contribution of international
      sociocultural factors and gender to the relationship between divorce and suicide.
      We conducted a systematic search of electronic databases to identify ecological
      studies reporting suicide rates and ratios of those rates within different
      marital statuses between Jan 1, 2000 and Dec 31, 2013. In total, ten studies
      consisting in suicide statistics of eleven countries/areas were selected. Using
      random-effect modeling, we noted that the pooled COA for men and women were 3.49
      (95% CI 2.43-4.56) and 3.15 (95% CI 1.74-4.56), suggesting both divorced men and
      women exhibited a greater risk of suicide than their married counterparts.
      Subgroup analyses revealed that COAs in Asian countries are significantly higher
      than those in non-Asian ones. Among the sociocultural measures retrieved from the
      HOFSTEDE index and the World Values Surveys, we noted significant associations
      between COA and four measures, including the individualism-collectivism score,
      the long-term orientation scores, the survival/self-expression score, and the
      gender inequality indices. The magnitudes and the directions of the associations
      however differ by sex. The results confirm that overall divorced people have an
      aggregate higher suicide risk than married ones. The method used in our research
      could reveal what cultural indicators are exerting effect on the relationship
      between divorce and suicide risk, which might change with sociocultural
      transition. More investigation into the relationships and then the construction
      of culturally appropriate suicide prevention policy is recommended. 

PMID- 25594955
TI  - Social contact frequency and all-cause mortality: a meta-analysis and meta
      regression.
AB  - Social contact frequency is a well-defined and relatively objective measure of
      social relationships, which according to many studies is closely associated with
      health and longevity. However, no previous meta-analysis has isolated this
      measure; existing reviews instead aggregate social contact with other diverse
      measures of social support, leaving unexplored the unique contribution of social
      contact to mortality. Furthermore, no study has sufficiently explored the factors
      that may moderate the relationship between contact frequency and mortality. We
      conducted meta-analyses and meta-regressions to examine 187 all-cause mortality
      risk estimates from 91 publications, providing data on about 400,000 persons. The
      mean hazard ratio (HR) for mortality among those with lower levels of social
      contact frequency was 1.13 (p < 0.05) among multivariate-adjusted HRs. However,
      sub-group meta-analyses show that there is no significant relationship between
      contact and mortality for male individuals and that contact with family members
      does not have a significant effect. The moderate effect sizes and the lack of
      association for some subgroups suggest that mere social contact frequency may not
      be as beneficial to one's health as previously thought.

PMID- 25594954
TI  - Household and neighborhood conditions partially account for associations between
      education and physical capacity in the National Health and Aging Trends Study.
AB  - Socioeconomic resources, such as education, prevent disability but are not
      readily modifiable. We tested the hypothesis that household and neighborhood
      conditions, which may be modifiable, partially account for associations between
      education and physical capacity in a population-based sample of older adults. The
      National Health and Aging Trends Study measured education (<high school, high
      school, some college, and >=Bachelor's), household and neighborhood conditions,
      using a 16-item environmental checklist and a 3-item social cohesion scale, and
      physical capacity with the Short Physical Performance Battery (SPPB), grip
      strength and peak expiratory flow. Structural equation models were used to
      decompose total educational effects into direct effects and indirect effects via
      household and neighborhood conditions, using sample weights and adjusting for
      age, sex, race/ethnicity, marital status, household size, BMI, self-reported
      health, and number of medical conditions in 6874 community-dwelling participants.
      Education was directly associated with SPPB scores (beta = 0.055, p < 0.05) and
      peak flow (beta = 0.095, p < 0.05), but not grip strength. Also, indirect effects
      were found for household disorder with SPPB scores (beta = 0.013, p < 0.05), grip
      strength (beta = 0.007, p < 0.05), and peak flow (beta = 0.010, p < 0.05).
      Indirect effects were also found for street disorder with SPPB scores (beta =
      0.012, p < 0.05). Indirect effects of household and neighborhood conditions
      accounted for approximately 35%, 27% and 14% of the total association between
      education and SPPB scores, grip strength level, and peak expiratory flow level,
      respectively. Household disorder and street disorder partially accounted for
      educational disparities in physical capacity. However, educational disparities in
      SPPB scores and peak expiratory flow persisted after accounting for household and
      neighborhood conditions and chronic conditions, suggesting additional pathways.
      Interventions and policies aiming to support aging in place should consider
      addressing household-level and street-level disorder.

PMID- 25594956
TI  - Impacts of the Affordable Care Act dependent coverage provision on health-related
      outcomes of young adults.
AB  - The first major insurance expansion of the Affordable Care Act - a provision
      requiring insurers to allow dependents to remain on parents' health insurance
      until turning 26 - took effect in September 2010. We estimate this mandate's
      impacts on numerous outcomes related to health care access, preventive care
      utilization, risky behaviors, and self-assessed health. We estimate difference-in
      differences models with 23-25 year olds as the treatment group and 27-29 year
      olds as the control group. For the full sample, the dependent coverage provision
      increased the probabilities of having health insurance, a primary care doctor,
      and excellent self-assessed health, while reducing body mass index. However, the
      mandate also increased risky drinking and did not lead to any significant
      increases in preventive care utilization. Subsample analyses reveal particularly
      large gains for men and college graduates. 

PMID- 25594957
TI  - Real-time closed-loop control of human heart rate and blood pressure.
AB  - Prolonged bed rest has significant negative impacts on the human body,
      particularly on the cardiovascular system. To overcome adverse effects and
      enhance functional recovery in bedridden patients, the goal is to mobilize
      patients as early as possible while controlling and stabilizing their
      cardiovascular system. In this paper, we used a robotic tilt table that allows
      early mobilization by modulating body inclination and automated leg movement to
      control the cardiovascular variables heart rate (HR) or systolic or diastolic
      blood pressures (sBP, dBP). The design and use of a control system is often done
      with a simulation model of a plant, but the time-variant and nonlinear nature of
      the cardiovascular system and subject-specific responses to external stimuli
      makes the modeling and identification challenging. Instead, we implemented an
      intelligent self-learning fuzzy controller that does not need any prior knowledge
      about the plant. The controller modulates the body inclination in order to adjust
      the cardiovascular parameters, with leg movement considered as a perturbing
      factor to the controller. The controller performance was evaluated in six healthy
      subjects. Measured mean values of HR, sBP, and dBP differed from desired
      reference values by 1.11 beats/min, 5.10 mmHg, and 2.69 mmHg, respectively. With
      this new control strategy, HR and dBP could be successfully controlled within
      medically tolerable ranges (deviations < 2.5 beats/min and < 5 mmHg from desired
      values, respectively). The control of sBP was less accurate; the results suggest
      that simultaneous control of multiple input stimuli rather than only adaptive
      automatic change of the tilt table angle might improve the controllability. 

PMID- 25594958
TI  - Sequential Hierarchical Agglomerative Clustering of White Matter Fiber Pathways.
AB  - OBJECTIVE: We consider the problem of clustering white matter fiber pathways,
      extracted from diffusion MRI data via tractography, into bundles that are
      consistent with the neuroanatomy. METHODS: We cast this problem as clustering
      streams of data, and use a sequential framework to process one fiber at a time.
      Our method, named as sequential hierarchical agglomerative clustering (HAC),
      represents the clusters with parametric models, performs HAC of relatively small
      number of fibers only when the parameters need to be initialized and/or updated,
      and assigns the labels to the following streams of data according to the current
      models. RESULTS: Experiments on phantom data evaluate the sensitivity of our
      method to initialization and parameter tuning, and show its advantages over
      alternative techniques. Experiments on real data demonstrate its efficacy and
      speed in clustering white matter fiber pathways into anatomically distinct
      bundles. CONCLUSION: Sequential HAC is a fast method that benefits from having a
      predefined number of clusters, and rapidly assigns labels to incoming data with
      high accuracy. It can be thought of as a mechanism that does clustering, while
      simultaneously accepting newly computed fibers; thereby, alleviating the burden
      of computing the distances between every pair of fibers in a tractogram.
      SIGNIFICANCE: Sequential HAC is a practical tool that can interactively cluster
      fiber pathways and can be integrated into fiber tracking, which will be very
      useful for clinical researchers and neuroanatomists.

PMID- 25594959
TI  - Visual analytics for early-phase complex engineered system design support.

PMID- 25594960
TI  - Visual and manual control for human-robot teleoperation.

PMID- 25594961
TI  - Vortex Filaments in Grids for Scalable, Fine Smoke Simulation.
AB  - Vortex modeling can produce attractive visual effects of dynamic fluids, which
      are widely applicable for dynamic media, computer games, special effects, and
      virtual reality systems. However, it is challenging to effectively simulate
      intensive and fine detailed fluids such as smoke with fast increasing vortex
      filaments and smoke particles. The authors propose a novel vortex filaments in
      grids scheme in which the uniform grids dynamically bridge the vortex filaments
      and smoke particles for scalable, fine smoke simulation with macroscopic vortex
      structures. Using the vortex model, their approach supports the trade-off between
      simulation speed and scale of details. After computing the whole velocity,
      external control can be easily exerted on the embedded grid to guide the vortex
      based smoke motion. The experimental results demonstrate the efficiency of using
      the proposed scheme for a visually plausible smoke simulation with macroscopic
      vortex structures. 

PMID- 25594962
TI  - Ultrasound Volume Projection Imaging for Assessment of Scoliosis.
AB  - The standing radiograph is used as a gold standard to diagnose spinal deformity
      including scoliosis, a medical condition defined as lateral spine curvature > 10
      degrees . However, the health concern of X-ray and large inter-observer variation
      of measurements on X-ray images have significantly restricted its application,
      particularly for scoliosis screening and close follow-up for adolescent patients.
      In this study, a radiation-free freehand 3-D ultrasound system was developed for
      scoliosis assessment using a volume projection imaging method. Based on the
      obtained coronal view images, two measurement methods were proposed using
      transverse process and spinous profile as landmarks, respectively. As a
      reliability study, 36 subjects (age: 30.1 +/-14.5; male: 12; female: 24) with
      different degrees of scoliosis were scanned using the system to test the inter-
      and intra-observer repeatability. The intra- and inter-observer tests indicated
      that the new assessment methods were repeatable, with ICC larger than 0.92. Small
      intra- and inter-observer variations of measuring spine curvature were observed
      for the two measurement methods (intra-: 1.4 +/-1.0 degrees  and 1.4 +/-1.1
      degrees ; inter-: 2.2 +/-1.6 degrees  and 2.5 +/-1.6 degrees ). The results also
      showed that the spinal curvature obtained by the new method had good linear
      correlations with X-ray Cobb's method (R2 = 0.8, p < 0.001, 29 subjects). These
      results suggested that the ultrasound volume projection imaging method can be a
      promising approach for the assessment of scoliosis, and further research should
      be followed up to demonstrate its potential clinical applications for mass
      screening and curve progression and treatment outcome monitoring of scoliosis
      patients.

PMID- 25594963
TI  - Multi-Target Tracking With Time-Varying Clutter Rate and Detection Profile:
      Application to Time-Lapse Cell Microscopy Sequences.
AB  - Quantitative analysis of the dynamics of tiny cellular and sub-cellular
      structures, known as particles, in time-lapse cell microscopy sequences requires
      the development of a reliable multi-target tracking method capable of tracking
      numerous similar targets in the presence of high levels of noise, high target
      density, complex motion patterns and intricate interactions. In this paper, we
      propose a framework for tracking these structures based on the random finite set
      Bayesian filtering framework. We focus on challenging biological applications
      where image characteristics such as noise and background intensity change during
      the acquisition process. Under these conditions, detection methods usually fail
      to detect all particles and are often followed by missed detections and many
      spurious measurements with unknown and time-varying rates. To deal with this, we
      propose a bootstrap filter composed of an estimator and a tracker. The estimator
      adaptively estimates the required meta parameters for the tracker such as clutter
      rate and the detection probability of the targets, while the tracker estimates
      the state of the targets. Our results show that the proposed approach can
      outperform state-of-the-art particle trackers on both synthetic and real data in
      this regime. 

PMID- 25594964
TI  - Cell Detection From Redundant Candidate Regions Under Nonoverlapping Constraints.
AB  - Cell detection in microscopy images is essential for automated cell behavior
      analysis including cell shape analysis and cell tracking. Robust cell detection
      in high-density and low-contrast images is still challenging since cells often
      touch and partially overlap, forming a cell cluster with blurry intercellular
      boundaries. In such cases, current methods tend to detect multiple cells as a
      cluster. If the control parameters are adjusted to separate the touching cells,
      other problems often occur: a single cell may be segmented into several regions,
      and cells in low-intensity regions may not be detected. To solve these problems,
      we first detect redundant candidate regions, which include many false positives
      but in turn very few false negatives, by allowing candidate regions to overlap
      with each other. Next, the score for how likely the candidate region contains the
      main part of a single cell is computed for each cell candidate using supervised
      learning. Then we select an optimal set of cell regions from the redundant
      regions under nonoverlapping constraints, where each selected region looks like a
      single cell and the selected regions do not overlap. We formulate this problem of
      optimal region selection as a binary linear programming problem under
      nonoverlapping constraints. We demonstrated the effectiveness of our method for
      several types of cells in microscopy images. Our method performed better than
      five representative methods, achieving an F-measure of over 0.9 for all data
      sets. Experimental application of the proposed method to 3-D images demonstrated
      that also works well for 3-D cell detection.

PMID- 25594965
TI  - Spinal Navigation and Imaging: History, Trends, and Future.
AB  - The clinical practice of spine navigation has rapidly grown with the development
      of image-based guidance. In this paper, a brief history of spinal navigation is
      presented and a review of clinical outcomes for 12,622 pedicle screws placed
      using the latest technology in the sacral, lumbar and thoracic regions. The
      clinical evidence demonstrate that intraoperative 3D image guided surgery has a
      96.8% success rate. A concluding section detailing existing barriers that limit
      more widespread adoption and future development efforts is presented.

PMID- 25594966
TI  - Multi-Modality Vertebra Recognition in Arbitrary Views Using 3D Deformable
      Hierarchical Model.
AB  - Computer-aided diagnosis of spine problems relies on the automatic identification
      of spine structures in images. The task of automatic vertebra recognition is to
      identify the global spine and local vertebra structural information such as spine
      shape, vertebra location and pose. Vertebra recognition is challenging due to the
      large appearance variations in different image modalities/views and the high
      geometric distortions in spine shape. Existing vertebra recognitions are usually
      simplified as vertebrae detections, which mainly focuses on the identification of
      vertebra locations and labels but cannot support further spine quantitative
      assessment. In this paper, we propose a vertebra recognition method using 3D
      deformable hierarchical model (DHM) to achieve cross-modality local vertebra
      location+pose identification with accurate vertebra labeling, and global 3D spine
      shape recovery. We recast vertebra recognition as deformable model matching,
      fitting the input spine images with the 3D DHM via deformations. The 3D model
      matching mechanism provides a more comprehensive vertebra location+pose+label
      simultaneous identification than traditional vertebra location+label detection,
      and also provides an articulated 3D mesh model for the input spine section.
      Moreover, DHM can conduct versatile recognition on volume and multi-slice data,
      even on single slice. Experiments show our method can successfully extract
      vertebra locations, labels, and poses from multi-slice T1/T2 MR and volume CT,
      and can reconstruct 3D spine model on different image views such as lumbar,
      cervical, even whole spine. The resulting vertebra information and the recovered
      shape can be used for quantitative diagnosis of spine problems and can be easily
      digitalized and integrated in modern medical PACS systems. 

PMID- 25594967
TI  - Multi-task pose-invariant face recognition.
AB  - Face images captured in unconstrained environments usually contain significant
      pose variation, which dramatically degrades the performance of algorithms
      designed to recognize frontal faces. This paper proposes a novel face
      identification framework capable of handling the full range of pose variations
      within +/-90 degrees  of yaw. The proposed framework first transforms the
      original pose-invariant face recognition problem into a partial frontal face
      recognition problem. A robust patch-based face representation scheme is then
      developed to represent the synthesized partial frontal faces. For each patch, a
      transformation dictionary is learnt under the proposed multi-task learning
      scheme. The transformation dictionary transforms the features of different poses
      into a discriminative subspace. Finally, face matching is performed at patch
      level rather than at the holistic level. Extensive and systematic experimentation
      on FERET, CMU-PIE, and Multi-PIE databases shows that the proposed method
      consistently outperforms single-task-based baselines as well as state-of-the-art
      methods for the pose problem. We further extend the proposed algorithm for the
      unconstrained face verification problem and achieve top-level performance on the
      challenging LFW data set.

PMID- 25594968
TI  - Multiview alignment hashing for efficient image search.
AB  - Hashing is a popular and efficient method for nearest neighbor search in large
      scale data spaces by embedding high-dimensional feature descriptors into a
      similarity preserving Hamming space with a low dimension. For most hashing
      methods, the performance of retrieval heavily depends on the choice of the high
      dimensional feature descriptor. Furthermore, a single type of feature cannot be
      descriptive enough for different images when it is used for hashing. Thus, how to
      combine multiple representations for learning effective hashing functions is an
      imminent task. In this paper, we present a novel unsupervised multiview alignment
      hashing approach based on regularized kernel nonnegative matrix factorization,
      which can find a compact representation uncovering the hidden semantics and
      simultaneously respecting the joint probability distribution of data. In
      particular, we aim to seek a matrix factorization to effectively fuse the
      multiple information sources meanwhile discarding the feature redundancy. Since
      the raised problem is regarded as nonconvex and discrete, our objective function
      is then optimized via an alternate way with relaxation and converges to a locally
      optimal solution. After finding the low-dimensional representation, the hashing
      functions are finally obtained through multivariable logistic regression. The
      proposed method is systematically evaluated on three data sets: 1) Caltech-256;
      2) CIFAR-10; and 3) CIFAR-20, and the results show that our method significantly
      outperforms the state-of-the-art multiview hashing techniques.

PMID- 25594969
TI  - Fiducial facial point extraction using a novel projective invariant.
AB  - Automatic extraction of fiducial facial points is one of the key steps to face
      tracking, recognition, and animation.Great facial variations, especially pose or
      viewpoint changes,typically degrade the performance of classical methods. Recent
      learning or regression-based approaches highly rely on the availability of a
      training set that covers facial variations as wide as possible. In this paper, we
      introduce and extend a novel projective invariant, named the characteristic
      number (CN), which unifies the collinearity, cross ratio, and geometrical
      characteristics given by more (6) points. We derive strong shape priors from CN
      statistics on a moderate size (515) of frontal upright faces in order to
      characterize the intrinsic geometries shared by human faces. We combine these
      shape priors with simple appearance based constraints, e.g., texture, edge, and
      corner, into a quadratic optimization. Thereafter, the solution to facial point
      extraction can be found by the standard gradient descent. The inclusion of these
      shape priors renders the robustness to pose changes owing to their invariance to
      projective transformations. Extensive experiments on the Labeled Faces in the
      Wild, Labeled Face Parts in the Wild and Helen database, and cross-set faces with
      various changes demonstrate the effectiveness of the CN-based shape priors
      compared with the state of the art.

PMID- 25594970
TI  - Registration of images with N -fold dihedral blur.
AB  - In this paper, we extend our recent registration method designed specifically for
      registering blurred images. The original method works for unknown blurs, assuming
      the blurring point-spread function (PSF) exhibits an N -fold rotational symmetry.
      Here, we also generalize the theory to the case of dihedrally symmetric blurs,
      which are produced by the PSFs having both rotational and axial symmetries. Such
      kind of blurs are often found in unfocused images acquired by digital cameras, as
      in out-of-focus shots the PSF typically mimics the shape of the shutter aperture.
      This makes our registration algorithm particularly well-suited in applications
      where blurred image registration must be used as a preprocess step of an image
      fusion algorithm, and where common registration methods fail, due to the amount
      of blur. We demonstrate that the proposed method leads to an improvement of the
      registration performance, and we show its applicability to real images by
      providing successful examples of blurred image registration followed by depth-of
      field extension and multichannel blind deconvolution.

PMID- 25594971
TI  - Quality of Grasping and the Role of Haptics in a 3-D Immersive Virtual Reality
      Environment in Individuals With Stroke.
AB  - Reaching and grasping parameters with and without haptic feedback were
      characterized in people with chronic post-stroke behaviors. Twelve (67 +/- 10
      years) individuals with chronic stroke and arm/hand paresis (Fugl-Meyer
      Assessment-Arm: >= 46/66 pts) participated. Three dimensional (3-D) temporal and
      spatial kinematics of reaching and grasping movements to three objects (can:
      cylindrical grasp; screwdriver: power grasp; pen: precision grasp) in a physical
      environment (PE) with and without additional haptic feedback and a 3-D virtual
      environment (VE) with haptic feedback were recorded. Participants reached,
      grasped and transported physical and virtual objects using similar movement
      strategies in all conditions. Reaches made in VE were less smooth and slower
      compared to the PE. Arm and trunk kinematics were similar in both environments
      and glove conditions. For grasping, stroke subjects preserved aperture scaling to
      object size but used wider hand apertures with longer delays between times to
      maximal reaching velocity and maximal grasping aperture. Wearing the glove
      decreased reaching velocity. Our results in a small group of subjects suggest
      that providing haptic information in the VE did not affect the validity of
      reaching and grasping movement. Small disparities in movement parameters between
      environments may be due to differences in perception of object distance in VE.
      Reach-to-grasp kinematics to smaller objects may be improved by better 3-D
      rendering. Comparable kinematics between environments and conditions is
      encouraging for the incorporation of high quality VEs in rehabilitation programs
      aimed at improving upper limb recovery.

PMID- 25594972
TI  - Simulation Study to Improve Focalization of a Figure Eight Coil by Using a
      Conductive Shield Plate and a Ferromagnetic Block.
AB  - A new method to improve the focalization and efficiency of the Figure of Eight
      (FOE) coil in rTMS is discussed in this paper. In order to decrease the half
      width of the distribution curve (HWDC), as well to increase the ratio of positive
      peak value to negative peak value (RPN) of the induced electric field, a shield
      plate with a window and a ferromagnetic block are assumed to enhance the positive
      peak value of the induced electrical field. The shield is made of highly
      conductive copper, and the block is made of highly permeable soft magnetic
      ferrite. A computer simulation is conducted on ANSYS(r) software to conduct the
      finite element analysis (FEA). Two comparing coefficients were set up to optimize
      the sizes of the shield window and the block. Simulation results show that a
      shield with a 60 mm * 30 mm sized window, together with a block 40 mm thick, can
      decrease the focal area of a FOE coil by 46.7%, while increasing the RPN by
      135.9%. The block enhances the peak value of the electrical field induced by a
      shield-FOE by 8.4%. A real human head model was occupied in this paper to further
      verify our method. 

PMID- 25594973
TI  - A comprehensive analysis of strength-based optimum signal detection in
      concentration-encoded molecular communication with spike transmission.
AB  - In this paper, a comprehensive analysis of strength-based optimum signal
      detection model has been presented for concentration-encoded molecular
      communication (CEMC) with spike (i.e., impulsive) transmission based on amplitude
      shift keying (ASK) and on-off keying (OOK) modulations. Strength-based optimum
      signal detection problem in diffusion-based CEMC system has been investigated in
      detail in the presence of both diffusion noise and intersymbol interference
      (ISI). The receiver for optimum signal detection has been developed theoretically
      and explained with both analytical and simulation results of binary signal
      detection. Results show that the receiver thus developed can detect CEMC symbols
      effectively; however, the performance is influenced by three main factors,
      namely, communication range, transmission data rate, and receiver memory. For
      both ASK and OOK receivers, exact and approximate detection performances have
      been derived analytically depending on the probabilistic nature of molecular
      availability and the relationship between mean and variance of signal strengths.
      Correspondingly, bit error rate (BER) performance of the optimum receiver in a
      single CEMC link is further evaluated under various scenarios through extensive
      simulation experiments. 

PMID- 25594974
TI  - Green Synthesis of Gold Nanoparticles by a Metal Resistant Arthrobacter
      nitroguajacolicus Isolated From Gold Mine.
AB  - Biosynthesis of gold nanoparticles would benefit from the development of clean,
      nontoxic and environmentally acceptable procedures concerning microorganisms from
      bacteria to fungi and even algae. Actinobacteria are soil bacteria which have the
      enormous ability as biotechnological tools. In this paper, we reported the
      biosynthesis of gold nanoparticles by a member of Arthrobacter genus isolated
      from Andaliyan gold mine in north-west of Iran. This metal resistance strain
      obtained from an acidophilic region ( ~ pH 5.6). The UV-vis and XRD spectra of
      the aqueous medium containing the strain and 1 mM HAuCl 4 for 24 h, demonstrated
      the formation of gold nanoparticles. TEM micrographs showed intra-extracellular
      production of gold nanoparticles with spherical shape and average size of 40 nm.
      The result of morphological and molecular tests revealed that the isolate was
      belonged to Atrhrobacter and has 100% similarity in 16SrRNA gene sequences to
      Arthrobacter nitroguajacolicus.

PMID- 25594975
TI  - Simulation of the Dynamics of Bacterial Quorum Sensing.
AB  - Quorum sensing (QS) is a signaling mechanism that pathogenic bacteria use to
      communicate and synchronize the production of exofactors to attack their hosts.
      Understanding and controlling QS is an important step towards a possible solution
      to the growing problem of antibiotic resistance. QS is a cooperative effort of a
      bacterial population in which some of the bacteria do not participate. This
      phenomenon is usually studied using game theory and the non-participating
      bacteria are modeled as cheaters that exploit the production of common goods
      (exofactors) by other bacteria. Here, we take a different approach to study the
      QS dynamics of a growing bacterial population. We model the bacterial population
      as a growing graph and use spectral graph theory to compute the evolution of its
      synchronizability. We also treat each bacterium as a source of signaling
      molecules and use the diffusion equation to compute the signaling molecule
      distribution. We formulate a cost function based on Lagrangian dynamics that
      combines the time-like synchronization with the space-like diffusion of signaling
      molecules. Our results show that the presence of non-participating bacteria
      improves the homogeneity of the signaling molecule distribution preventing thus
      an early onset of exofactor production and has a positive effect on the
      optimization of QS signaling and on attack synchronization.

PMID- 25594976
TI  - Theoretical Analysis of Metallic Nanoparticles on Blood Flow Through Tapered
      Elastic Artery With Overlapping Stenosis.
AB  - The purpose of the present analysis is to discuss mathematical model of blood
      flow through an elastic artery with overlapping stenosis under the influence of
      metallic nanoparticles. The metallic nanoparticles analysis for the blood flow
      with overlapping stenosis is not explored so far. The governing equations for a
      mild stenosis case have been modeled to obtain exact solutions of velocity
      profile, temperature profile and pressure gradient. The expressions of impedance
      resistance to flow and wall shear stress are computed. The effects of different
      emerging flow parameters are discussed through graphs for different values of
      interest. At the end, the contribution of metallic nanoparticles reveals that is
      important to reduce the significances of the wall shear stress and resistance
      impedance to flow.

PMID- 25594977
TI  - Heterogeneous network model to infer human disease-long intergenic non-coding RNA
      associations.
AB  - With the knowledge of molecular biology it is highlighting that long non-coding
      RNAs (lncRNAs) play a critical role in many important biological processes, such
      as imprinting control, cell differentiation, immune responses, human diseases,
      tumorigenesis and other biological processes. This study proposes a novel
      computational method, named KRWRH, to infer disease-lincRNA associations with the
      influence of phenotype information and tissue expression details of lincRNA.
      Gaussian interaction profile kernel is calculated for diseases and lincRNAs and
      random walk with restart method is used for final prediction. The proposed method
      KRWRH is compared with four existing methods: LRLSLDA, TslncRNA, NRWRH, and RWRH.
      The experimental results based on the leave-one-out cross validation, ROC curves,
      and mean enrichment show that the proposed method KRWRH is able to predict known
      and unknown disease-lincRNA associations more effectively. 

PMID- 25594978
TI  - Detecting SNP combinations discriminating human populations from HapMap data.
AB  - The genomes of different human beings are similar. There are only a relatively
      small number of genetic differences between people. The genetic differences
      between people are very worthy of study. Researchers have proposed the fixation
      index FST measurement to find the single nucleotide polymorphisms (SNPs) which
      can reflect human population differences. However, most SNPs have interactions
      and they work together, which leads to the differences among human populations.
      The number of all possible m-locus combinations chosen from n SNPs grows
      exponentially. Most methods concern on 2-locus interactions. In this paper, we
      propose a novel method to find a new coordinate system under which the energy
      distributions of different populations are quite different. We select out
      candidate SNPs from n SNPs by using the information of the axes in the coordinate
      system. The number of candidate SNPs is small, thus SNP-SNP interactions can be
      searched efficiently. The method can also find interactions of more than two
      loci. These interactions should be able to reflect the evolution of human
      populations from another way. The numbers of SNP-SNP interactions are regarded as
      the differences between pairwise populations and a hierarchical clustering
      algorithm is used to construct the evolutionary tree. In the experiments, we
      apply the method to SNP data of four chromosomes separately and the trees
      constructed on these four chromosomes are highly consistent. Furthermore, the
      trees are also consistent with previous studies, which indicates that
      evolutionary information is well mined. The method provides a new insight to
      analyze the human population differences. 

PMID- 25594980
TI  - Controllable surface haptics via particle jamming and pneumatics.
AB  - The combination of particle jamming and pneumatics allows the simultaneous
      control of shape and mechanical properties in a tactile display. A hollow
      silicone membrane is molded into an array of thin cells, each filled with coffee
      grounds such that adjusting the vacuum level in any individual cell rapidly
      switches it between flexible and rigid states. The array clamps over a pressure
      regulated air chamber with internal mechanisms designed to pin the nodes between
      cells at any given height. Various sequences of cell vacuuming, node pinning, and
      chamber pressurization allow the surface to balloon into a variety of shapes.
      Experiments were performed to expand existing physical models of jamming at the
      inter-particle level to define the rheological characteristics of jammed systems
      from a macroscopic perspective, relevant to force-displacement interactions that
      would be experienced by human users. Force-displacement data show that a jammed
      cell in compression fits a Maxwell model and a cell deflected in the center while
      supported only at the edges fits a Zener model, each with stiffness and damping
      parameters that increase at higher levels of applied vacuum. This provides
      framework to tune and control the mechanical properties of a jamming haptic
      interface. 

PMID- 25594982
TI  - A kernel adaptive algorithm for quaternion-valued inputs.
AB  - The use of quaternion data can provide benefit in applications like robotics and
      image recognition, and particularly for performing transforms in 3-D space. Here,
      we describe a kernel adaptive algorithm for quaternions. A least mean square
      (LMS)-based method was used, resulting in the derivation of the quaternion kernel
      LMS (Quat-KLMS) algorithm. Deriving this algorithm required describing the idea
      of a quaternion reproducing kernel Hilbert space (RKHS), as well as kernel
      functions suitable with quaternions. A modified HR calculus for Hilbert spaces
      was used to find the gradient of cost functions defined on a quaternion RKHS. In
      addition, the use of widely linear (or augmented) filtering is proposed to
      improve performance. The benefit of the Quat-KLMS and widely linear forms in
      learning nonlinear transformations of quaternion data are illustrated with
      simulations. 

PMID- 25594981
TI  - Memristor-based multilayer neural networks with online gradient descent training.
AB  - Learning in multilayer neural networks (MNNs) relies on continuous updating of
      large matrices of synaptic weights by local rules. Such locality can be exploited
      for massive parallelism when implementing MNNs in hardware. However, these update
      rules require a multiply and accumulate operation for each synaptic weight, which
      is challenging to implement compactly using CMOS. In this paper, a method for
      performing these update operations simultaneously (incremental outer products)
      using memristor-based arrays is proposed. The method is based on the fact that,
      approximately, given a voltage pulse, the conductivity of a memristor will
      increment proportionally to the pulse duration multiplied by the pulse magnitude
      if the increment is sufficiently small. The proposed method uses a synaptic
      circuit composed of a small number of components per synapse: one memristor and
      two CMOS transistors. This circuit is expected to consume between 2% and 8% of
      the area and static power of previous CMOS-only hardware alternatives. Such a
      circuit can compactly implement hardware MNNs trainable by scalable algorithms
      based on online gradient descent (e.g., backpropagation). The utility and
      robustness of the proposed memristor-based circuit are demonstrated on standard
      supervised learning tasks. 

PMID- 25594979
TI  - Toward Automating Clinical Assessments: A Survey of the Timed Up and Go.
AB  - Older adults often suffer from functional impairments that affect their ability
      to perform everyday tasks. To detect the onset and changes in abilities,
      healthcare professionals administer standardized assessments. Recently,
      technology has been utilized to complement these clinical assessments to gain a
      more objective and detailed view of functionality. In the clinic and at home,
      technology is able to provide more information about patient performance and
      reduce subjectivity in outcome measures. The timed up and go (TUG) test is one
      such assessment recently instrumented with technology in several studies,
      yielding promising results toward the future of automating clinical assessments.
      Potential benefits of technological TUG implementations include additional
      performance parameters, generated reports, and the ability to be self
      administered in the home. In this paper, we provide an overview of the TUG test
      and technologies utilized for TUG instrumentation. We then critically review the
      technological advancements and follow up with an evaluation of the benefits and
      limitations of each approach. Finally, we analyze the gaps in the implementations
      and discuss challenges for future research toward automated self-administered
      assessment in the home. 

PMID- 25594983
TI  - VC-dimension of univariate decision trees.
AB  - In this paper, we give and prove the lower bounds of the Vapnik-Chervonenkis (VC)
      dimension of the univariate decision tree hypothesis class. The VC-dimension of
      the univariate decision tree depends on the VC-dimension values of its subtrees
      and the number of inputs. Via a search algorithm that calculates the VC-dimension
      of univariate decision trees exhaustively, we show that our VC-dimension bounds
      are tight for simple trees. To verify that the VC-dimension bounds are useful, we
      also use them to get VC-generalization bounds for complexity control using
      structural risk minimization in decision trees, i.e., pruning. Our simulation
      results show that structural risk minimization pruning using the VC-dimension
      bounds finds trees that are more accurate as those pruned using cross validation.

PMID- 25594984
TI  - Hierarchical cooperative control for multiagent systems with switching directed
      topologies.
AB  - The hierarchical cooperative control problem is concerned for a two-layer
      networked multiagent system under switching directed topologies. The group
      cooperative objective is to achieve finite-time formation control for the upper
      layer of leaders and containment control for the lower layer of followers. Two
      kinds of cooperative strategies, including centralized-distributed control and
      distributed-distributed control, are proposed for two types of switching laws: 1)
      random switching law with the dwell time and 2) Markov switching law with
      stationary distribution. Utilizing the state transition matrix methods and matrix
      measure techniques, some sufficient conditions are derived for asymptotical
      containment control and exponential almost sure containment control,
      respectively. Finally, some numerical examples are provided to demonstrate the
      effectiveness of the proposed control schemes. 

PMID- 25594985
TI  - Lag Synchronization of Switched Neural Networks via Neural Activation Function
      and Applications in Image Encryption.
AB  - This paper investigates the problem of global exponential lag synchronization of
      a class of switched neural networks with time-varying delays via neural
      activation function and applications in image encryption. The controller is
      dependent on the output of the system in the case of packed circuits, since it is
      hard to measure the inner state of the circuits. Thus, it is critical to design
      the controller based on the neuron activation function. Comparing the results, in
      this paper, with the existing ones shows that we improve and generalize the
      results derived in the previous literature. Several examples are also given to
      illustrate the effectiveness and potential applications in image encryption. 

PMID- 25594986
TI  - Estimating Oxygen Uptake During Nonsteady-State Activities and Transitions Using
      Wearable Sensors.
AB  - In this paper, we present a method to estimate oxygen uptake ( VO2) during daily
      life activities and transitions between them. First, we automatically locate
      transitions between activities and periods of nonsteady-state VO2. Subsequently,
      we propose and compare activity-specific linear functions to model steady-state
      activities and transition-specific nonlinear functions to model nonsteady-state
      activities and transitions. We evaluate our approach in study data from 22
      participants that wore a combined accelerometer and heart rate sensor while
      performing a wide range of activities (clustered into lying, sedentary,
      dynamic/household, walking, biking and running), including many transitions
      between intensities, thus resulting in nonsteady-state VO2. Indirect calorimetry
      was used in parallel to obtain VO2 reference. VO2 estimation error during
      transitions between sedentary, household and walking activities could be reduced
      by 16% on average using the proposed approach, compared to state of the art
      methods. 

PMID- 25594987
TI  - Beat-by-Beat Quantification of Cardiac Cycle Events Detected From Three
      Dimensional Precordial Acceleration Signals.
AB  - The vibrations produced by the cardiovascular system that are coupled to the
      precordium can be noninvasively detected using accelerometers. This technique is
      called seismocardiography. Although clinical applications have been proposed for
      seismocardiography, the physiology underlying the signal is still not clear. The
      relationship of seismocardiograms of on the back-to-front axis and cardiac events
      is fairly well known. However, the 3-D seismocardiograms detectable with modern
      accelerometers have not been quantified in terms of cardiac cycle events. A major
      reason for this might be the degree of intersubject variability observed in 3-D
      seismocardiograms. We present a method to quantify 3-D seismocardiography in
      terms of cardiac cycle events. First, cardiac cycle events are identified from
      the seismocardiograms, and then, assigned a number based on the location in which
      the corresponding event was found. 396 cardiac cycle events from 9 healthy
      subjects and 120 cardiac cycle events from patients suffering from atrial flutter
      were analyzed. Despite the weak intersubject correlation of the waveforms (0.05,
      0.27, and 0.15 for the x-, y-, and z-axes, respectively), the present method
      managed to find latent similarities in the seismocardiograms of healthy subjects.
      We observed that in healthy subjects the distribution of cardiac cycle event
      coordinates was centered on specific locations. These locations were different in
      patients with atrial flutter. The results suggest that spatial distribution of
      seismocardiographic cardiac cycle events might be used to discriminate healthy
      individuals and those with a failing heart. 

PMID- 25594988
TI  - Design and Evaluation of an Interactive Exercise Coaching System for Older
      Adults: Lessons Learned.
AB  - Although the positive effects of exercise on the well-being and quality of
      independent living for older adults are well accepted, many elderly individuals
      lack access to exercise facilities, or the skills and motivation to perform
      exercise at home. To provide a more engaging environment that promotes physical
      activity, various fitness applications have been proposed. Many of the available
      products, however, are geared toward a younger population and are not appropriate
      or engaging for an older population. To address these issues, we developed an
      automated interactive exercise coaching system using the Microsoft Kinect. The
      coaching system guides users through a series of video exercises, tracks and
      measures their movements, provides real-time feedback, and records their
      performance over time. Our system consists of exercises to improve balance,
      flexibility, strength, and endurance, with the aim of reducing fall risk and
      improving performance of daily activities. In this paper, we report on the
      development of the exercise system, discuss the results of our recent field pilot
      study with six independently living elderly individuals, and highlight the
      lessons learned relating to the in-home system setup, user tracking, feedback,
      and exercise performance evaluation. 

PMID- 25594989
TI  - Optic Disc Localization in Retinal Images Based on Cumulative Sum Fields.
AB  - This paper describes an automatic method for the optic disc localization in
      retinal images, which is effective and reliable with multiple datasets.
      Particularly, the described method reveals very effective dealing with retinal
      images with large pathological signs. The algorithm begins with a new vessel
      enhancement method based on a modified corner detector. Subsequently, a weighted
      version of the vessel enhancement is combined with morphological operators, to
      detect the four main vessels orientations {0( degrees ), 45( degrees ), 90(
      degrees ), 135( degrees ) }. These four image functions have all the necessary
      information to determine an initial optic disc localization, resulting in two
      images that are respectively divided along the vertical or horizontal
      orientations with different division sizes. Each division is averaged creating a
      2-D step function, and a cumulative sum of the different sizes step functions is
      calculated in the vertical and horizontal orientations, resulting in an initial
      optic disc position. The final optic disc localization is determined by a vessel
      convergence algorithm using its two most relevant features; high vasculature
      convergence and high intensity values. The proposed method was evaluated in eight
      publicly available datasets, including the STARE and DRIVE datasets. The optic
      disc was localized correctly in 1752 out of the 1767 retinal images (99.15%) with
      an average computation time of 18.34 s. 

PMID- 25594990
TI  - A Study on Estimation of Joint Force Through Isometric Index Finger Abduction
      With the Help of SEMG Peaks for Biomedical Applications.
AB  - We propose a new method to estimate joint force using a biomechanical muscle
      model and peaks of surface electromyography (SEMG). The SEMG measurement was
      carried out from the first dorsal interosseous muscle during isometric index
      finger abduction. The SEMG peaks were used as the input of the biomechanical
      muscle model which is a transfer function to generate the force. The force
      estimation performance ( R(2) ) was evaluated using the proposed method with nine
      healthy subjects, and a former method using a mean absolute value (MAV), which is
      the full-wave rectified and averaged (or low-pass filtered) signal of SEMG in a
      time window, was compared with the proposed method; the performance of the
      proposed method (0.94 +/- 0.03) was better than that of MAV (0.90 +/- 0.02). The
      proposed method could be widely applied to quantitative analysis of muscle
      activities based on SEMG. 

PMID- 25594991
TI  - Observed-Based Adaptive Fuzzy Tracking Control for Switched Nonlinear Systems
      With Dead-Zone.
AB  - In this paper, the problem of adaptive fuzzy output-feedback control is
      investigated for a class of uncertain switched nonlinear systems in strict
      feedback form. The considered switched systems contain unknown nonlinearities,
      dead-zone, and immeasurable states. Fuzzy logic systems are utilized to
      approximate the unknown nonlinear functions, a switched fuzzy state observer is
      designed and thus the immeasurable states are obtained by it. By applying the
      adaptive backstepping design principle and the average dwell time method, an
      adaptive fuzzy output-feedback tracking control approach is developed. It is
      proved that the proposed control approach can guarantee that all the variables in
      the closed-loop system are bounded under a class of switching signals with
      average dwell time, and also that the system output can track a given reference
      signal as closely as possible. The simulation results are given to check the
      effectiveness of the proposed approach. 

PMID- 25594992
TI  - Artificial Bee Colony Algorithm Based on Information Learning.
AB  - Inspired by the fact that the division of labor and cooperation play extremely
      important roles in the human history development, this paper develops a novel
      artificial bee colony algorithm based on information learning (ILABC, for short).
      In ILABC, at each generation, the whole population is divided into several
      subpopulations by the clustering partition and the size of subpopulation is
      dynamically adjusted based on the last search experience, which results in a
      clear division of labor. Furthermore, the two search mechanisms are designed to
      facilitate the exchange of information in each subpopulation and between
      different subpopulations, respectively, which acts as the cooperation. Finally,
      the comparison results on a number of benchmark functions demonstrate that the
      proposed method performs competitively and effectively when compared to the
      selected state-of-the-art algorithms. 

PMID- 25594993
TI  - Multiagent Learning of Coordination in Loosely Coupled Multiagent Systems.
AB  - Multiagent learning (MAL) is a promising technique for agents to learn efficient
      coordinated behaviors in multiagent systems (MASs). In MAL, concurrent multiple
      distributed learning processes can make the learning environment nonstationary
      for each individual learner. Developing an efficient learning approach to
      coordinate agents' behaviors in this dynamic environment is a difficult problem,
      especially when agents do not know the domain structure and have only local
      observability of the environment. In this paper, a coordinated MAL approach is
      proposed to enable agents to learn efficient coordinated behaviors by exploiting
      agent independence in loosely coupled MASs. The main feature of the proposed
      approach is to explicitly quantify and dynamically adapt agent independence
      during learning so that agents can make a trade-off between a single-agent
      learning process and a coordinated learning process for an efficient decision
      making. The proposed approach is employed to solve two-robot navigation problems
      in different scales of domains. Experimental results show that agents using the
      proposed approach can learn to act in concert or independently in different areas
      of the environment, which results in great computational savings and near optimal
      performance. 

PMID- 25594994
TI  - Life history strategy and the HEXACO personality dimensions.
AB  - Although several studies have linked Life History Strategy (LHS) variation with
      variation in the Five Factor Model personality dimensions, no published research
      has explored the relationship of LHS to the HEXACO personality dimensions. The
      theoretically expected relationship of the HEXACO Emotionality factor to LHS is
      unclear. The results of two studies (N = 641) demonstrated that LHS indicators
      form part of a factor along with HEXACO Extraversion, Agreeableness,
      Conscientiousness, and (marginally) Honesty-Humility. People higher on these
      dimensions pursue a slower LHS. Neither Openness nor Emotionality was associated
      with this factor. Holding LHS constant, social involvement with kin was
      consistently predicted by higher Emotionality and was not consistently predicted
      by any other HEXACO factor. These results support a view of Emotionality as part
      of an LHS-independent personality dimension that influences the provision and
      receipt of kin altruism. 

PMID- 25594995
TI  - What constitutes high performance in priority setting and resource allocation?
      Decision maker narratives identified from a survey and qualitative study in
      Canadian healthcare organizations.
AB  - Priority setting and resource allocation are key management functions; however,
      there may be different understandings as to what makes for a high-performing
      organization in this area. To interpret how decision makers actually approach
      this question, our research looks at what might contribute to one's reputation as
      such. Two sets of qualitative data are used. Senior healthcare leaders were asked
      to nominate organizations which they considered high performers in priority
      setting and resource allocation and to justify their choices. This open-ended
      question was analyzed to identify themes. Rigorous process was most often cited.
      Six case studies were subsequently conducted; respondents were asked to comment
      upon why they thought their organization might be named by others as a high
      performer. These replies were analyzed qualitatively to identify prominent
      storylines: three distinctive narratives are summarized here. These help us to
      understand how organization leaders in particular contexts bring together
      stakeholders to pursue locally appropriate strategies for achieving contextually
      defined high performance.

PMID- 25594996
TI  - Factors associated with hospital closure and merger: a survival analysis of Dutch
      hospitals from 1978 to 2010.
AB  - Health policy in most West European countries is directed at transforming the
      healthcare systems into more self-regulating and competitive systems. After a
      period of strong regulation, the Dutch government decided to step back and
      created conditions in which competition could lead to cost management and quality
      improvement. The question is whether mergers have contributed to the survival
      chances of hospitals. This paper describes the results of an analysis performed
      on the survival of all Dutch hospitals in the years 1978 to 2010. The survival of
      hospitals during this period was determined and their survival rates were
      calculated statistically. Furthermore, the relation between a hospital's lifespan
      and a number of predictive variables was investigated. In this study, more
      detailed consideration is given to the fact of whether a hospital merged with
      another hospital. Bivariate analysis shows that smaller hospitals in particular
      have been driven out of the market. The difference in lifespan between hospitals
      which had merged and those which had not, appeared to be significant. However, a
      multivariate analysis, when corrected for size, type, and location, showed that
      merging had no significant effect on hospital lifespan. 

PMID- 25594997
TI  - Sweat the small stuff: a case study of small-scale change processes and
      consequences in acute care.
AB  - Solving small, annoying problems may appear to be unimportant in a political,
      demographic, and economic climate that focuses attention on radical long-term
      changes to the organization, delivery, funding, and regulation of the healthcare
      system. Most contemporary commentary emphasizes the need for large-scale, major,
      strategic, transformational change. Deliberately designed to focus on minor
      issues, however, the intervention reported here, in a hospital gastroenterology
      department, demonstrates how small changes generate major benefits for patients,
      staff, and hospital performance. This approach can also strengthen clinical
      managerial relationships, which are key to larger scale changes and which suffer
      when 'the small stuff' is not fixed. The success of this intervention is
      explained with reference to a model of change combining context, content,
      process, and individual dispositions. The intervention, however, is easily
      modified to suit different contexts and was subsequently used successfully in
      other service areas in the same hospital. These outcomes present a challenge to
      the contemporary preoccupation with transformational change. Healthcare managers
      are thus advised, on the basis of this experience, to be alert to what appear to
      be minor unresolved issues, and to address these rapidly, in addition to larger
      scale, longer term projects. 

PMID- 25594998
TI  - The balance of care approach to health and social care planning: lessons from a
      systematic literature review.
AB  - The strategic allocation of resources is one the most difficult tasks facing
      health and social care decision makers, with multiple organisations delivering
      complex services to heterogeneous populations. The enduring appeal of the balance
      of care approach, a systematic framework for exploring the potential costs and
      consequences of changing the mix of community and institutional services in a
      defined geographical area, is thus unsurprising. However, no attempt has
      previously been made to synthesise or appraise the methodological approaches
      employed and lessons to inform future applications may go unheard. This paper
      seeks to address those concerns by reporting the findings of a systematic
      literature review that identified 33 examples of the model's use spanning 40
      years. The majority of studies were undertaken in the UK and explored the
      services needed by frail older people. There is, however, nothing in the model to
      restrict it to this context. The paper also details the different ways key
      elements of the model (information about clients, resources, the appraisal of
      settings, costs and outcomes) have been operationalised, and considers their
      strengths and weaknesses. Whilst several studies identified a potential to reduce
      costs via the use of less institutional care, not all applications predicted cost
      savings. 

PMID- 25594999
TI  - Leadership and transformational change in healthcare organisations: a qualitative
      analysis of the North East Transformation System.
AB  - The research project 'An Evaluation of Transformational Change in NHS North East'
      examines the progress and success of National Health Service (NHS) organisations
      in north east England in implementing and embedding the North East Transformation
      System (NETS), a region-wide programme to improve healthcare quality and safety,
      and to reduce waste, using a combination of Vision, Compact, and Lean-based
      Method. This paper concentrates on findings concerning the role of leadership in
      enabling tranformational change, based on semi-structured interviews with a mix
      of senior NHS managers and quality improvement staff in 14 study sites. Most
      interviewees felt that implementing the NETS requires committed, stable
      leadership, attention to team-building across disciplines and leadership
      development at many levels. We conclude that without senior leader commitment to
      continuous improvement over a long time scale and serious efforts to distribute
      leadership tasks to all levels, healthcare organisations are less likely to
      achieve positive changes in managerial-clinical relations, sustainable
      improvements to organisational culture and, ultimately, the region-wide step
      change in quality, safety and efficiency that the NETS was designed to deliver. 

PMID- 25595000
TI  - EHMA briefing: knowledge mobilization in European Union funded projects - the
      dialogue model.

PMID- 25595001
TI  - Comparing the content of leadership theories and managers' shared perceptions of
      effective leadership: a Q-method study of trainee managers in the English NHS.
AB  - Health service managers face potential conflicts between corporate and
      professional agendas, a tension sharpened for trainees by their junior status and
      relative inexperience. While academic leadership theory forms an integral part of
      contemporary management development programmes, relatively little is known of
      trainees' patterned subjectivities in relation to leadership theories. The
      objective of this study was to explore such subjectivities within a cohort of
      trainees on the National Health Service Graduate Management Training Scheme (NHS
      GMTS), a 'fast-track' programme which prepares graduate entrants for director
      level health service management posts. A Q-method design was used and four shared
      subjectivities were identified: leadership as collaborative social process
      ('relational'); leadership as integrity ('moral'); leadership as effective
      support of subordinates ('team'); and leadership as construction of a credible
      leadership persona ('identity'). While the factors broadly map onto competencies
      indicated within the NHS Leadership Qualities Framework which underpin
      assessments of performance for this student group, it is important not to
      overstate the governance effect of the assessment regime. Rather, factors reflect
      tensions between required competencies, namely the mobilisation of diverse
      interest groups, the ethical base of decisions and the identity work required to
      convince others of leadership status. Indeed, factor 2 ('moral') effectively
      defines leadership as the embodiment of public service ethos. 

PMID- 25595002
TI  - Dynamics of ambulatory surgery centers and hospitals market entry.
AB  - In this article, we investigate the diversity of healthcare delivery
      organizations by comparing the market determinants of hospitals entry rates with
      those of ambulatory surgery centers (ASCs). Unlike hospitals, ASCs is one of the
      growing populations of specialized healthcare delivery organizations. There are
      reasons to believe that firm entry patterns differ within growing organizational
      populations since these markets are characterized by different levels of
      organizational legitimacy, technological uncertainty, and information asymmetry.
      We compare the entry patterns of firms in a mature population of hospitals to
      those of firms within a growing population of ASCs. By using patient-level
      datasets from the state of Florida, we break down our explanatory variables by
      facility type (ASC vs. hospital) and utilize negative binomial regression models
      to evaluate the impact of niche density on ASC and hospital entry. Our results
      indicate that ASCs entry rates is higher in markets with overlapping ASCs while
      hospitals entry rates are less in markets with overlapping hospitals and ASCs.
      These results are consistent with the notion that firms in growing populations
      tend to seek out crowded markets as they compete to occupy the most desirable
      market segments while firms in mature populations such as general hospitals avoid
      direct competition. 

PMID- 25595003
TI  - Frameworks for change in healthcare organisations: a formative evaluation of the
      NHS Change Model.
AB  - BACKGROUND: Organisational change in complex healthcare systems is a multifaceted
      process. The English National Health Service recently introduced a 'Change Model'
      that seeks to offer an evidence-based framework for guiding change. We report
      findings from a formative evaluation of the NHS Change Model and make
      recommendations for those developing the Model and its users. METHODS: The
      evaluation involved 28 interviews with managers and clinicians making use of the
      Change Model in relation to a variety of projects. Interviews were fully
      transcribed and were analysed using an approach based on the Framework method.
      FINDINGS: Participants saw the Change Model as valuable and practically useful.
      Fidelity to core principles of the Model was variable: participants often altered
      the Model, especially when using it to orchestrate the work of others. In
      challenging organisational contexts, the Change Model was sometimes used to
      delegitimise opposition rather than identify shared purpose among different
      interest groups. CONCLUSIONS: Those guiding change may benefit from frameworks,
      guidance and toolkits to structure and inform their planning and activities.
      Participants' experiences suggested the Change Model has much potential. Further
      work on its design and on supporting materials may optimise the approach, but its
      utility rests in particular on organisational cultures that support faithful
      application.

PMID- 25595004
TI  - Health management education in Europe and in the United States: a comparative
      review and analysis.
AB  - In Europe and in the United States, health management education and the role of
      health managers are patterned and consistent with how the country's healthcare
      system is organized, managed, and financed. In the United States, the fee-for
      service, entrepreneurial dominated approach, resulting in health being one of the
      few remaining growth industries, has created a huge demand for additional health
      management education programs and managers. Therefore, universities finding
      themselves in an economic slump are attracted to establish health services
      administration programs (a North American term) since they require limited
      capital, continue to attract enrollment, and contribute to the "social good." In
      contrast, the European countries' healthcare systems provide universal access to
      care and strict, governmental fiscal control on healthcare expenditures. As a
      result, the American masters-level health manager model has not thrived there-
      although not willingly conceded is the fact that in Europe physicians continue to
      dominate the management ranks. After outlining a number of the current problems
      facing US health management education, this article focuses on: (1) a projected
      shuttering of the weaker American health management programs and the market for
      health managers being overly saturated (such as for lawyers now), because the US
      gross domestic product expenditures for health will decrease over the next two
      decades from the current level of 17.6% to be somewhat comparable to the 11.5% in
      Canada, France, and Germany; and (2) a projected increase in the enrollment among
      European health management programs for several reasons: (a) a huge spike in the
      demand for additional clinically oriented, health managers who can trade off
      concerns of cost versus quality; and (b) the constraints of most countries'
      statutory health insurance plans will become increasingly more evident so that
      privatization of healthcare services will become an option for those with above
      average incomes and, thereby, generate a demand for newly minted health managers
      similar to the US masters-level graduate.

PMID- 25595005
TI  - What causes international variations in length of stay: a comparative analysis
      for two inpatient conditions in Japanese and Canadian hospitals.
AB  - Hospital average length of stay varies considerably between countries. However,
      there is limited patient-level research identifying or discounting possible
      reasons for these differences. This study compares the length of stay of patients
      in Japan, where it is the longest in the OECD, and Canada, where length of stay
      is closer to the OECD mean. Administrative patient-level data, including age,
      gender, co-morbidities, intervention, discharge plan, outcome and length of stay
      were collected from two Japanese and two Ontario, Canada hospitals for two
      diagnoses: colorectal cancer surgery and acute myocardial infarction. Analyses
      examined linkages between patient characteristics, hospitals and countries and
      length of stay. When controlling for patient demographic characteristics, the
      incidence of co-morbidities and discharge plan practices, Japanese length of stay
      tended to be significantly longer than that in Canada for both diagnoses.
      Mortality rates were not significantly different; however, the readmission rate
      (28 days or less) for acute myocardial infarction was higher in the Canadian
      hospitals. The findings indicate that non-clinical factors contribute to
      sustained international differences in length of stay. These factors may include
      professional or cultural norms, differing payment schemes and access to long-term
      care facilities. The study also introduces a protocol that can be used for
      international patient-level comparisons that can enable effective policy and
      management learning. 

PMID- 25595006
TI  - How patients choose hospitals: using the stereotypic content model to model
      trustworthiness, warmth and competence.
AB  - In many countries, policy initiatives force the implementation of demand-driven
      healthcare systems to encourage competition among providers. When actively
      choosing hospitals, consumers can compare data on the quality of hospital
      performance among providers. However, patients do not necessarily take full
      advantage of comparative quality information but instead use a number of readily
      available proxies to evaluate provider trustworthiness. According to the
      stereotypic content model, organizational trustworthiness is built on
      stereotypical perceptions of hospitals' competence and warmth, reflected by
      visible hospital characteristics such as ownership and teaching status, and size.
      We introduce a theoretical framework on stereotypic quality perceptions that
      brings together fragmented findings in health services research on patient
      quality expectations of hospital characteristics. The model provides a basis for
      further research and recommendations for improved hospital communication
      strategies. The study suggests that researchers as well as hospital management
      should pay more attention to stereotypical patient quality perceptions and their
      impact on hospital choice to understand patients' quality evaluations better. 

PMID- 25595007
TI  - A theoretical and empirical investigation into the willingness-to-pay function
      for new innovative drugs by Germany's health technology assessment agency
      (IQWiG).
AB  - Under the recently enacted pharmaceutical price and reimbursement regulation in
      Germany, new drugs are subject to a rapid assessment to determine whether there
      is sufficient evidence of added clinical benefits compared with the existing
      standard of treatment. If such added benefits are confirmed, manufacturers and
      representatives of the Statutory Health Insurance (SHI) are expected to negotiate
      an appropriate reimbursement price. If parties fail to reach an agreement, a
      final decision on the reimbursement price will be made by an arbitration body. If
      one of the parties involved wishes so, then the Institute for Quality and
      Efficiency in Health Care (Institut fur Qualitat und Wirtschaftlichkeit im
      Gesundheitswesen, IQWiG) will be commissioned with a formal evaluation of costs
      and benefits of the product in question. IQWiG will make a recommendation for a
      reimbursement price based on the 'efficiency frontier' in a therapeutic area. The
      purpose of the assessments is to provide support for decision-making bodies that
      act on behalf of the SHI insurants. To determine the willingness to pay for new
      drugs, IQWiG uses the following decision rule: the incremental cost-effectiveness
      ratio of a new drug compared with the next effective intervention should not be
      higher than that of the next effective intervention compared with its comparator.
      The purpose of this paper was to investigate the theoretical and empirical
      relationship between the willingness to pay for drugs and their health benefits.
      The analysis shows that across disease areas IQWiG has a curvilinear relationship
      between willingness to pay and health benefits. Future research may address the
      validity of the willingness-to-pay function from the viewpoint of the individual
      SHI insurants. 

PMID- 25595008
TI  - Hospital characteristics affecting potentially avoidable emergency admissions:
      national ecological study.
AB  - Some emergency admissions can be avoided if acute exacerbations of health
      problems are managed by emergency and urgent care services without resorting to
      admission to a hospital bed. In England, these services include hospitals,
      emergency ambulance, and a range of primary and community services. The aim was
      to identify whether characteristics of hospitals affect potentially avoidable
      emergency admission rates. An age-sex adjusted rate of admission for 14
      conditions rich in avoidable emergency admissions was calculated for 129
      hospitals in England for 2008-2011. Twenty-two per cent (3,273,395/14,998,773) of
      emergency admissions were classed as potentially avoidable, with threefold
      variation between hospitals. Explanatory factors of this variation included those
      which hospital managers could not control (demand for hospital emergency
      departments) and those which they could control (supply in terms of numbers of
      acute beds in the hospital, and management of non-emergency and emergency
      patients within the hospital). Avoidable admission rates were higher for
      hospitals with higher emergency department attendance rates, higher numbers of
      acute beds per 1000 catchment population and higher conversion rates from
      emergency department attendance to admission. Hospital managers may be able to
      reduce avoidable emergency admissions by reducing supply of acute beds and
      conversion rates from emergency department attendance. 

PMID- 25595010
TI  - The use of memoranda of understanding in fostering inter-agency collaboration: a
      qualitative study of health services agencies serving vulnerable populations in
      Baltimore, USA.
AB  - INTRODUCTION: We examined whether mandated collaboration reflected in memoranda
      of understanding (MOUs) developed by health agencies to meet funder expectations
      is effective in fostering inter-agency collaboration. METHODS: We conducted 22
      semi-structured interviews from late 2010 to early 2012 in Baltimore, USA, with
      representatives of 17 HIV service agencies, three local health department units,
      and one agency that closed in 2008 (two interviews). RESULTS: While there was no
      consensus, most respondents perceived MOUs negatively, mainly because the process
      of obtaining signed MOUs was time consuming; frontline staff was mostly unaware
      of MOUs, agencies did not necessarily work with agencies they signed MOUs with
      and MOUs were rarely evaluated after being signed. A few agencies reported that
      MOUs could keep agencies focused and set mutual expectations. The local health
      department acknowledged shortcomings in MOUs but emphasized that MOUs could help
      agencies plan for referring clients when their own capacity was full.
      CONCLUSIONS: Although many agencies acknowledged the importance of collaboration,
      most respondents found that MOUs lacked practical utility. Grant-makers should
      consult sub-grantees to develop alternative means of fostering collaboration that
      would be perceived as relevant by both parties.

PMID- 25595011
TI  - Understanding patient nutrition: a case study of the organizational and
      managerial dimension to good clinical care.

PMID- 25595009
TI  - Medical leadership arrangements in English healthcare organisations: findings
      from a national survey and case studies of NHS trusts.
AB  - This project sought to describe the involvement of doctors in leadership roles in
      the NHS and the organisational structures and management processes in use in NHS
      trusts. A mixed methods approach was adopted combining a questionnaire survey of
      English NHS trusts and in-depth case studies of nine organisations who responded
      to the survey. Respondents identified a number of challenges in the development
      of medical leadership, and there was often perceived to be an engagement gap
      between medical leaders and doctors in clinical roles. While some progress has
      been made in the development of medical leadership in the NHS in England, much
      remains to be done to complete the journey that started with the Griffiths Report
      in 1983. We conclude that a greater degree of professionalism needs to be brought
      to bear in the development of medical leadership. This includes developing career
      structures to make it easier for doctors to take on leadership roles; providing
      training, development and support in management and leadership at different
      stages of doctors' careers; and ensuring that pay and other rewards are
      commensurate with the responsibilities of medical leaders. The time commitment of
      medical leaders and the proportion of doctors in leadership roles both need to
      increase. The paper concludes considering the implications of these findings for
      other health systems. 

PMID- 25595012
TI  - Organisational readiness and Lean Thinking implementation: findings from three
      emergency department case studies in New Zealand.
AB  - This paper describes and contrasts the implementation of Lean Thinking - a
      quality methodology that emphasises waste reduction and performing at higher
      levels of productivity with the same or less resources - into New Zealand's
      healthcare system. As the field is relatively new, three literature-based
      exemplar cases were developed to provide an analysis framework to analyse the
      three New Zealand research sites, which had activities, teamwork, leadership and
      sustainability as its core themes. Each research site's case was developed from
      primary data gathered through interviews, augmented by secondary data from
      project reports, District Health Board websites and media stories. The results
      highlight the benefits of a supportive quality-focussed organisational culture,
      executive management involvement and cross-functional teams as enablers. Further,
      work intensification and workplace resistance were also evident in varying levels
      within the sites. The study, while reiterating the problems of introducing
      quality methods from other domains into healthcare, presents the New Zealand
      context and reinforces that organisational preparedness as a significant factor
      which contributes to implementation success. This study goes beyond
      investigations of the use of Lean tools, changing improvement metrics and
      descriptive statistics to identify the contexts and variables which surround
      quality and process improvement implementations.

PMID- 25595013
TI  - Applying the concept of consumer confusion to healthcare: development and
      validation of a patient confusion model.
AB  - As patient autonomy and consumer sovereignty increase, information provision is
      considered essential to decrease information asymmetries between healthcare
      service providers and patients. However, greater availability of third party
      information sources can have negative side effects. Patients can be confused by
      the nature, as well as the amount, of quality information when making choices
      among competing health care providers. Therefore, the present study explores how
      information may cause patient confusion and affect the behavioral intention to
      choose a health care provider. Based on a quota sample of German citizens (n =
      198), the present study validates a model of patient confusion in the context of
      hospital choice. The study results reveal that perceived information overload,
      perceived similarity, and perceived ambiguity of health information impact the
      affective and cognitive components of patient confusion. Confused patients have a
      stronger inclination to hastily narrow down their set of possible decision
      alternatives. Finally, an empirical analysis reveals that the affective and
      cognitive components of patient confusion mediate perceived information overload,
      perceived similarity, and perceived ambiguity of information. 

PMID- 25595014
TI  - Leadership in academic health centers in the US: a review of the role and some
      recommendations.
AB  - The leadership of the US's most complex academic health centers (AHCs)/medical
      centers requires individuals who possess a high level of clinical,
      organizational, managerial, and interpersonal skills. This paper first outlines
      the major attributes desired in a dean/vice president of health affairs before
      then summarizing the educational opportunities now generally available to train
      for such leadership and management roles. For the most part, the masters in
      health administration (MHA), the traditional MBA, and the numerous alternatives
      primarily available at universities are considered far too general and too
      lacking in emotional intelligence tutoring to be particularly relevant for those
      who aspire to these most senior leadership positions. More appropriate
      educational options for these roles are discussed: (a) the in-house leadership
      and management programs now underway at some AHCs for those selected early on in
      their career for future executive-type roles as well as for those who are
      appointed later on to a chair, directorship or similar position; and (b) a more
      controversial approach of potentially establishing at one or a few universities,
      a mid-career, professional program (a maximum of 12 months and therefore, being
      completed in less time than an MBA) leading to a masters degree in academic
      health center administration (MHCA) for those who aspire to fill a senior AHC
      leadership position. The proposed curriculum as outlined herein might be along
      the lines of some carefully designed masters level on-line, self-teaching modules
      for the more technical subjects, yet vigorously emphasizing integrate-type
      courses focused on enhancing personal and professional team building and
      leadership skills. 

PMID- 25595015
TI  - Interventions to reduce bullying in health care organizations: a scoping review.
AB  - The problem of staff-to-staff bullying and its consequences in the health care
      sector has given rise to urgent knowledge needs among health care employers,
      union representatives, and professional associations. The purpose of this scoping
      review is to increase the uptake and application of synthesized research results
      of interventions designed to address bullying among coworkers within health care
      workplaces. The scoping review's methodology uses an adapted version of the
      Arksey and O'Malley framework to locate and review empirical studies involving
      interventions designed to address bullying in health care workplaces. The
      findings of the review reveal eight articles from three countries discussing
      interventions that included educative programming, bullying champions/advocates,
      and zero-tolerance policies. The reported evaluations extend beyond bullying to
      include organizational culture, trust in management, retention rates, and
      psychosocial health. The most promising reported outcomes are from participatory
      interventions. The results of the review make a compelling case for bullying
      interventions based on participatory principles. 

PMID- 25595016
TI  - Unwarranted variations in healthcare: time for a European agenda.

PMID- 25595017
TI  - Word on the Street: Engaging Local Leaders in a Dialogue About Prostate Cancer
      Among African Americans.
AB  - African American men face the highest rates of prostate cancer, yet with no
      consensus for screening and treatment, making informed health care decisions is
      difficult. This study aimed to identify approaches to empowering African American
      men as proactive participants in prostate cancer decision making using an
      established community-campus partnership employing elements of community-based
      participatory research methods. Community stakeholders with an interest in, and
      knowledge about, health care in two local African American communities were
      recruited and completed key informant interviews (N = 39). Grounded theory coding
      identified common themes related to prostate cancer knowledge, beliefs,
      attitudes, and responses to them. Common barriers such as gender roles, fear, and
      fatalism were identified as barriers to work-up and treatment, and both
      communities' inadequate and inaccurate prostate cancer information described as
      the key problem. To build on community strengths, participants said the change
      must come from inside these communities, not be imposed from the outside. To
      accomplish this, they suggested reaching men through women, connecting men to
      doctors they can trust, making men's cancer education part of broader health
      education initiatives designed as fun and inexpensive family entertainment
      events, and having churches bring community members in to speak on their
      experiences with cancer. This study demonstrated the success of community
      engagement to identify not only barriers but also local strengths and
      facilitators to prostate cancer care in two suburban/rural African American
      communities. Building collaboratively on community strengths may improve prostate
      cancer care specifically and health care in general.

PMID- 25595018
TI  - A Comparative Study of Australian and New Zealand Male and Female Nurses' Health:
      A Sex Comparison and Gender Analysis.
AB  - The aim of this research was to compare the health and lifestyle behaviors
      between male and female nursing professionals. Biological, workplace, and
      lifestyle factors as well as health behaviors and outcomes are reported as
      different between male and female nurses. Although male nurses show distinct
      health-related patterns and experience health disparities at work, few studies
      have investigated health differences by sex in a large cohort group of nursing
      professionals. This observation study of Australian and New Zealand nurses and
      midwives drew data from an eCohort survey. A cohort of 342 females was generated
      by SPSS randomization (total N=3625), to compare against 342 participating males.
      Measures for comparison include health markers and behaviors, cognitive well
      being, workplace and leisure-time vitality, and functional capacity. Findings
      suggest that male nurses had a higher BMI, sat for longer, slept for less time,
      and were more likely to be a smoker than their female nurse counterparts. Men
      were more likely to report restrictions in bending, bathing, and dressing. In
      relation to disease, male nurses reported greater rates of respiratory disease
      and cardiovascular disease, including a three times greater incidence of
      myocardial infarction, and were more likely to have metabolic problems. In
      contrast, however, male nurses were more likely to report feeling calm and
      peaceful with less worries about their health. Important for nurse workforce
      administrators concerned about the well-being of their staff, the current study
      reveals significant sex differences and supports the need for gender-sensitive
      approaches to aid the well-being of male nurses.

PMID- 25595020
TI  - Gender-Atypical Mental Illness as Male Gender Threat.
AB  - The present study examined whether men view gender-atypical (i.e., feminine)
      psychological disorders as threats to their gender status. Men and women (N =
      355) rated their expectations of gender status loss, feelings of distress, and
      help-seeking intentions in response to 10 different stereotypically masculine and
      feminine psychological disorders. Men as compared to women expected greater
      gender status loss for, and reported more distress to, gender-atypical versus
      gender-typical disorders. Expectations of gender status loss partially mediated
      the link between participant gender and distress at the thought of gender
      atypical disorders. These findings suggest that feminine disorders pose more
      powerful gender status threats for men than masculine disorders do and that men's
      expectations of gender status loss for feminine disorders drive their negative
      reactions to these mental illnesses. The discussion emphasizes the importance of
      considering the gender-typicality of disorders, and the implications of these
      findings for clinical interventions.

PMID- 25595019
TI  - Gender Differences in Weight-Related Attitudes and Behaviors Among Overweight and
      Obese Adults in the United States.
AB  - Few studies have used nationally representative data to focus specifically on
      gender differences in weight-related outcomes. This article examines gender
      differences in weight-related outcomes across the body mass index (BMI) spectrum
      in overweight and obese adults. Data from the National Health and Nutrition
      Examination Survey 2009-2010 was analyzed. Weight-related outcomes were accurate
      weight perception, weight dissatisfaction, attempted weight loss, successful
      weight loss, and weight loss strategies. Compared with women, overweight and
      obese men were less likely to have accurate weight perception (odds ratio [OR] =
      0.36; 95% confidence interval [CI] = 0.30-0.44), weight dissatisfaction (OR =
      0.39; 95% CI = 0.32-0.47), and attempted weight loss (OR = 0.55; 95% CI = 0.48
      0.63). The modifying effect of gender on these associations decreased as BMI
      increased. By BMI 35, the mean probability of women and men to have accurate
      weight perception and weight dissatisfaction was 90%; attempted weight loss was
      60% (women) and 50% (men). At lower BMIs, men had up to 40% less probability than
      women for these weight loss outcomes. Men who attempted weight loss were more
      likely than women to lose and maintain >=10 lb over 1 year (OR = 1.41; 95% CI =
      1.20-1.65) and increase exercise and eat less fat as weight loss strategies;
      women were more likely to join weight loss programs, take prescription diet
      pills, and follow special diets. A need exists for male-specific interventions to
      improve overweight and obese men's likelihood for accurate weight perception,
      attempted weight loss, and ultimately, successful weight loss.

PMID- 25595021
TI  - Has Their Son Been Vaccinated? Beliefs About Other Parents Matter for Human
      Papillomavirus Vaccine.
AB  - The goal of this study was to determine if parents' beliefs about social norms of
      human papillomavirus (HPV) vaccination for sons were associated with knowledge of
      HPV, intention to vaccinate sons, or beliefs about side effects. A cross
      sectional, survey-based study of parents with sons was performed in 2010.
      Fisher's exact tests were used to examine associations between demographics and
      responses about social norms. Multivariate logistic regression models examined
      beliefs about social norms of male HPV vaccination and primary outcomes. Few
      parents agreed that others were vaccinating sons (n = 31/267, 12%), including 1%
      responding strongly agree and 11% responding agree. Most parents, 52%, disagreed
      that others were vaccinating (40% disagree, 11% strongly disagree), and 37% chose
      prefer not to answer regarding others' vaccination practices. Hispanic parents
      and those with a high school education or less were significantly more likely to
      choose prefer not to answer than their respective counterparts regarding
      vaccination norms. In multivariate models, parents agreeing others were
      vaccinating sons had greater odds of having high knowledge of HPV (adjusted odds
      ratio [aOR] high vs low knowledge 3.15, 95% confidence interval [CI] 1.13, 8.77)
      and increased intention to vaccinate sons (n = 243, aOR = 4.41, 95% CI = 1.51,
      12.89). Beliefs about side effects were not significantly associated with beliefs
      about social norms. Parents' beliefs about others' vaccination practices are
      important with regard to knowledge of HPV and intention to vaccinate sons.
      Studying how various public messages about HPV vaccine may influence normative
      beliefs could be relevant to improving vaccination coverage.

PMID- 25595022
TI  - Intraprotein signal transduction by HAMP domains: a balancing act.
AB  - HAMP domains are small protein modules that predominantly operate as signal
      transducers in bacterial sensor proteins most of which are membrane delimited.
      The domain organization of such sensors has the HAMPs localized at the
      intersection between the membrane-anchored input sensor and the cytosolic output
      machinery. The data summarized here indicate that HAMP modules use a universal
      signaling language in balancing the communication between diverse membrane-bound
      input domains and cytosolic output domains that are completely foreign to each
      other. 

PMID- 25595023
TI  - Synthesis of the spore envelope in the developmental life cycle of Streptomyces
      coelicolor.
AB  - Members of the family of Streptomycetaceae, the main producer of antibiotics and
      other secondary metabolites, are Gram-positive multi-cellular soil bacteria with
      a complex life cycle. By apical tip extension Streptomyces coelicolor forms a
      multiply branching vegetative mycelium penetrating the substrate. Upon nutrient
      limitation, a hydrophobic aerial mycelium is erected, which eventually develops
      into a regular chain of spores that are able to survive detrimental environmental
      conditions. Morphological differentiation involves a switch in the peptidoglycan
      synthesizing machinery. Whereas apical tip extension is directed by the so-called
      polarisome, sporulation septation and synthesis of the thickened spore wall
      involves a multi-protein complex, which resembles the elongasome of rod-shaped
      bacteria. The Streptomyces spore wall synthesizing complex (SSSC) does not only
      direct synthesis of the peptidoglycan layer but is also involved in the
      incorporation of anionic spore wall glycopolymers, which contribute to the
      resistance of spores. The SSSC also contains eukaryotic type serine/threonine
      kinases which might control its activity by protein-phosphorylation. 

PMID- 25595024
TI  - Synthesis and function of phospholipids in Staphylococcus aureus.
AB  - Phospholipids are the major components of bacterial membranes, and changes in
      phospholipid composition affect important cellular processes such as metabolism,
      stress response, antimicrobial resistance, and virulence. The most prominent
      phospholipids in Staphylococcus aureus are phosphatidylglycerol, lysyl
      phosphatidylglycerol, and cardiolipin, whose biosynthesis is mediated by a
      complex protein machinery. Phospholipid composition of the staphylococcal
      membrane has to be continuously adjusted to changing external conditions, which
      is achieved by a series of transcriptional and biochemical regulatory mechanisms.
      This mini-review outlines the current state of knowledge concerning synthesis,
      regulation, and function of the major staphylococcal phospholipids. 

PMID- 25595025
TI  - Identification of in vivo-induced bacterial protein antigens during calf
      infection with Chlamydia psittaci.
AB  - Chlamydia (C.) psittaci, the causative agent of ornithosis, is an obligate
      intracellular pathogen with a unique developmental cycle and a high potential for
      zoonotic transmission. Various mammalian hosts, such as cattle, horse, sheep and
      man that are in close contact with contaminated birds can get infected (referred
      to as psittacosis). Since little is known about long-term sequelae of chronic
      disease and the molecular mechanisms of chlamydial pathogenesis, a key step in
      understanding the in vivo situation is the identification of C. psittaci
      infection-associated proteins. For this, we investigated sera of infected calves.
      Using the immunoscreening approach In Vivo Induced Antigen Technology (IVIAT)
      including all relevant controls, we focused on C. psittaci proteins, which are
      induced in vivo during infection. Sera were pooled, extensively adsorbed against
      in vitro antigens to eliminate false positive results, and used to screen an
      inducible C. psittaci 02DC15 genomic expression library. Screening and control
      experiments revealed 19 immunogenic proteins, which are expressed during
      infection. They are involved in transport and oxidative stress response, heme and
      folate biosynthesis, DNA replication, recombination and repair, cell envelope,
      bacterial secretion systems and hypothetical proteins of so far unknown
      functions. Some of the proteins found may be considered as diagnostic markers or
      as candidates for the development of vaccines. 

PMID- 25595026
TI  - Global analysis of bacterial membrane proteins and their modifications.
AB  - Membrane proteins are situated at the interface of bacterial cell and its
      environment, and are therefore involved in vital physiological processes such as
      nutrient exchange, signal transduction and virulence. Due to their distinct
      biophysical properties, especially hydrophobicity, they are difficult subjects to
      study. Classical proteomics technologies have relied on multidimensional
      separation of proteins on gels, which largely limited the choice of detergents
      and made the development of specialized enrichment protocols for membrane
      proteins necessary. Shotgun proteomic approaches, based on the digestion of whole
      proteomes and subsequent analysis of peptides by LC-MS, has largely circumvented
      these problems due to its compatibility with potent detergents. Here we briefly
      present and discuss the major developments in bacterial membrane proteomics and
      argue that recent developments in biochemical sample preparation and high
      resolution mass spectrometry have the potential to comprehensively identify and
      quantify membrane proteins without the need for specific enrichment procedures
      prior to LC-MS analysis. 

PMID- 25595027
TI  - Classification of body dysmorphic disorder - what is the advantage of the new DSM
      5 criteria?
AB  - OBJECTIVE: In DSM-5 the diagnosis of body dysmorphic disorder (BDD) has been
      subjected to two important changes: Firstly, BDD has been assigned to the
      category of obsessive-compulsive and related disorders. Secondly, a new criterion
      has been defined requiring the presence of repetitive behaviors or mental acts in
      response to appearance concerns. The aims of this study were to report the
      prevalence rates of BDD based on a DSM-5 diagnosis, and to evaluate the impact of
      the recently introduced DSM-5 criteria for BDD by comparing the prevalence rates
      (DSM-5 vs. DSM-IV) METHODS: BDD-criteria (DSM-IV/DSM-5), dysmorphic concerns, and
      depressive symptoms, were assessed in a representative sample of the German
      general population (N=2129, aged 18-65years). RESULTS: The association between
      BDD case identification based on DSM-IV and DSM-5 was strong (Phi=.95, p<.001),
      although point prevalence of BDD according to DSM-5 was slightly lower (2.9%,
      n=62 vs. 3.2%, n=68). Approximately one third of the identified BDD (DSM-5) cases
      reported time-consuming behavioral acts in response to appearance concerns. In
      detail, 0.8% of the German general population fulfilled the BDD criteria and
      reported repetitive acts of at least one hour/day. CONCLUSIONS: The revised
      criteria of BDD in DSM-5 do not seem to have an impact on prevalence rates.
      However, the recently added B-criterion reflects more precisely the clinical
      symptoms of BDD, and may be useful for distinguishing between various severity
      levels related to repetitive behaviors/mental acts.

PMID- 25595028
TI  - Cancer immunotherapy utilizing gene-modified T cells: From the bench to the
      clinic.
AB  - The immune system plays a critical role in the elimination and suppression of
      pathogens. Although the endogenous immune system is capable of immune
      surveillance resulting in the elimination of cancer cells, tumor cells have
      developed a variety of mechanisms to escape immune recognition often resulting in
      tumor outgrowth. The presence of immune infiltrate in tumors has been correlated
      with a good prognosis following treatment (Sato et al., 2005; Loi et al., 2013;
      Clemente et al., 1996; Galon et al., 2006). As such, immune cells such as T
      cells, have been harnessed in order to target cancer. Tumor reactive lymphocytes,
      called tumor-infiltrating lymphocytes (TILs) have been isolated and expanded from
      the tumor and reinfused back into patients for the treatment of melanoma. The
      promise of adoptive immunotherapy utilizing TILs as a robust treatment for cancer
      has been highlighted in patients with advanced melanoma with greater than 50% of
      patients responding to treatment (Dudley et al., 2005). Although TIL therapy has
      shown promising results in melanoma patients, it has proved difficult to
      translate this approach to other cancers, given that the numbers of TILs that can
      be isolated are generally low. To broaden this therapy for other cancers, T cells
      have been genetically modified to endow them with tumor reactivity using either a
      T cell receptor (TCR) (Parkhurst et al., 2009, 2011; Chinnasamy et al., 2011) or
      a chimeric antigen receptor (CAR) (Grupp et al., 2013; Park et al., 2007). This
      review will outline the origins and development of adoptive immunotherapy
      utilizing TILs leading to genetic modification strategies to redirect T cells to
      cancer. Potential hurdles and novel strategies will be discussed for realizing
      the full potential of adoptive immunotherapy becoming a standard of care
      treatment for cancer. 

PMID- 25595029
TI  - Toward stratified treatments for bipolar disorders.
AB  - In bipolar disorders, there are unclear diagnostic boundaries with unipolar
      depression and schizophrenia, inconsistency of treatment guidelines, relatively
      long trial-and-error phases of treatment optimization, and increasing use of
      complex combination therapies lacking empirical evidence. These suggest that the
      current definition of bipolar disorders based on clinical symptoms reflects a
      clinically and etiologically heterogeneous entity. Stratification of treatments
      for bipolar disorders based on biomarkers and improved clinical markers are
      greatly needed to increase the efficacy of currently available treatments and
      improve the chances of developing novel therapeutic approaches. This review
      provides a theoretical framework to identify biomarkers and summarizes the most
      promising markers for stratification regarding beneficial and adverse treatment
      effects. State and stage specifiers, neuropsychological tests, neuroimaging, and
      genetic and epigenetic biomarkers will be discussed with respect to their ability
      to predict the response to specific pharmacological and psychosocial
      psychotherapies for bipolar disorders. To date, the most reliable markers are
      derived from psychopathology and history-taking, while no biomarker has been
      found that reliably predicts individual treatment responses. This review
      underlines both the importance of clinical diagnostic skills and the need for
      biological research to identify markers that will allow the targeting of
      treatment specifically to sub-populations of bipolar patients who are more likely
      to benefit from a specific treatment and less likely to develop adverse
      reactions.

PMID- 25595030
TI  - Obstructive Sleep Apnea as a Predictor of Atrial Fibrillation After Coronary
      Artery Bypass Grafting.

PMID- 25595031
TI  - Minimally invasive coronary bypass in a patient with metal allergy.
AB  - Patients with metal allergy represent a challenge for current surgical
      techniques, particularly minimally invasive ones, in which metal implants are
      routinely used to facilitate procedures. We report on a 60-year-old woman with
      metal allergy who presented with non-ST elevation myocardial infarction, and in
      whom we performed minimally invasive coronary artery bypass via small
      thoracotomy. In conclusion, we show that minimally invasive coronary surgery
      might feasibly be done without the aid of metal implants or surgical clips for
      hemostasis. 

PMID- 25595032
TI  - How long should resuscitative efforts be continued in adult out-of-hospital
      cardiac arrest?
AB  - The neurological prognosis of out-of-hospital cardiac arrest (OHCA) is extremely
      poor, particularly in patients who require prolonged cardiopulmonary
      resuscitation (CPR). However, the upper limit of CPR duration is unclear. We
      present a case of a 51-year-old man with nonhypothermic OHCA. He was discharged
      without neurological sequelae despite long duration CPR lasting 143 minutes,
      which is the longest duration among adult nonhypothermic OHCA cases reported.
      There are some patients for whom CPR duration might not be associated with
      prognosis. To determine when to terminate resuscitative efforts or whether more
      lifesaving medical resources should be provided, a prognostic indicator other
      than CPR duration is needed. 

PMID- 25595033
TI  - First application of coronary flow reserve measurement for the assessment of left
      main compression syndrome in pulmonary hypertension.
AB  - Left main compression syndrome (LMCS) refers to extrinsic compression of the left
      main coronary artery because of a dilated pulmonary artery trunk. The condition
      represents an unusual cause of angina, left ventricular dysfunction, and sudden
      cardiac death in patients with pulmonary hypertension. We present 2 patients with
      the syndrome who were followed with serial assessments of coronary flow reserve
      by transthoracic echocardiography to screen for LMCS-related ischemia. 

PMID- 25595034
TI  - Obesity and breastfeeding: The strength of association.
AB  - Obesity and attendant co-morbidities are an emergent problem in public health.
      Much attention has focused on prevention, especially during the perinatal period.
      Breastfeeding is considered a possible protective factor for obesity in
      childhood, influencing gene-neuroendocrine-environment-lifestyle interaction.
      Therefore, breastfeeding and its longer duration are probably associated with
      lower development of childhood obesity. Through human milk, but not formula, the
      child assumes greater bioactive factors contributing to immunological, endocrine,
      development, neural and psychological benefits. Contrarily, other studies did not
      confirm a critical role of breast milk. Confounding factors, especially maternal
      pre-pregnancy overweight, may influence breastfeeding effects. This review
      summarises what is known about the possible relationship between breastfeeding
      and prevention of obesity development. CONCLUSION: Breastfeeding appears to
      represent a protective factor for obesity in childhood, although evidence is
      still controversial and underlying mechanisms unclear. Further research is needed
      to improve knowledge on overweight/obesity and breastfeeding.

PMID- 25595035
TI  - Qualitative study on the socio-cultural determinants of care of children orphaned
      by AIDS in the Ashanti and Eastern regions of Ghana.
AB  - BACKGROUND: Almost three decades after the discovery of HIV and AIDS in Ghana,
      the most obvious impact of the disease is the growing orphan crisis affecting
      most families and communities, especially in areas that the prevalence of HIV has
      exceeded the epidemic's threshold of 5%. Studies have indicated that these
      orphans usually experience a wide range of problems which include education,
      nutrition, physical and sexual abuse, emotional and psychological distress,
      stigma and discrimination, among others The aim of the study was to examine the
      social, cultural, and traditional norms and practices that influence the care of
      children orphaned by AIDS in Ghana. METHODS: The study employed focus group
      discussions, in-depth interviews and key informant interviews to generate
      information on the socio-cultural factors that impact orphan care in the Ashanti
      and Eastern regions of Ghana. RESULTS: The findings indicated that the cultural
      practices that influence how well an AIDS orphan is taken care of by their
      caregivers include traditional rituals, ceremonies, and norms like funeral rites,
      marriage and naming ceremonies, festivals, inheritance, polygyny, and puberty
      rites. The social factors mentioned to affect orphan care significantly were:
      excessive alcohol drinking, and tobacco and drug use, dressing with fashion,
      night club attendance, market days, stigma and discrimination, among others.
      CONCLUSION: It is recommended that though some cultural and traditional practices
      are deeply rooted in communities and cannot be done away completely, orphan care
      policies on interventions should take into account these factors to mitigate
      their effects on the care of orphans.

PMID- 25595036
TI  - Refusal to enrol in Ghana's National Health Insurance Scheme: is affordability
      the problem?
AB  - BACKGROUND: Access to health insurance is expected to have positive effect in
      improving access to healthcare and offer financial risk protection to households.
      Ghana began the implementation of a National Health Insurance Scheme (NHIS) in
      2004 as a way to ensure equitable access to basic healthcare for all residents.
      After a decade of its implementation, national coverage is just about 34% of the
      national population. Affordability of the NHIS contribution is often cited by
      households as a major barrier to enrolment in the NHIS without any rigorous
      analysis of this claim. In light of the global interest in achieving universal
      health insurance coverage, this study seeks to examine the extent to which
      affordability of the NHIS contribution is a barrier to full insurance for
      households and a burden on their resources. METHODS: The study uses data from a
      cross-sectional household survey involving 2,430 households from three districts
      in Ghana conducted between January-April, 2011. Affordability of the NHIS
      contribution is analysed using the household budget-based approach based on the
      normative definition of affordability. The burden of the NHIS contributions to
      households is assessed by relating the expected annual NHIS contribution to
      household non-food expenditure and total consumption expenditure. Households
      which cannot afford full insurance were identified. RESULTS: Results show that
      66% of uninsured households and 70% of partially insured households could afford
      full insurance for their members. Enroling all household members in the NHIS
      would account for 5.9% of household non-food expenditure or 2.0% of total
      expenditure but higher for households in the first (11.4%) and second (7.0%)
      socio-economic quintiles. All the households (29%) identified as unable to afford
      full insurance were in the two lower socio-economic quintiles and had large
      household sizes. Non-financial factors relating to attributes of the insurer and
      health system problems also affect enrolment in the NHIS. CONCLUSION:
      Affordability of full insurance would be a burden on households with low socio
      economic status and large household size. Innovative measures are needed to
      encourage abled households to enrol. Policy should aim at abolishing the
      registration fee for children, pricing insurance according to socio-economic
      status of households and addressing the inimical non-financial factors to
      increase NHIS coverage.

PMID- 25595037
TI  - Postmortem CT morphometry with a proposal of novel parameters for sex
      discrimination of the mandible using Japanese adult data.
AB  - Major human sex differences in the mandible after adolescence include the overall
      size as well as the shape of the chin and mandibular angle; however, objective
      interpretation of discrimination accuracy is difficult for these morphological
      indicators. The present study investigated measurements of the mandible for sex
      discrimination using postmortem CT morphometry in forensic autopsy cases of
      Japanese subjects after adolescence (age>16 years; male, n=116, and female,
      n=106), including the proposal of novel parameters representing the overall
      mandibular size and shape. The distance between the gnathion and condylus (gn
      cdl), and bigonial width (go-go), as well as the angle formed by bilateral gn-cdl
      lines (Agn-cdl), correlated with bicondylar breadth (cdl-cdl), independent of the
      body height, showing no significant sex difference. The distance from the gn to
      the cdl-cdl line (oblique length), the ratio of Agn-cdl to cdl-cdl, and the
      oblique triangular area formed by bilateral gn-cdl and cdl-cdl lines (Deltaobl),
      which were proposed as indicators of chin protrusion, showed significant sex
      differences (p<0.001). Overall sensitivity and specificity at respective
      discriminating points for sex estimation were 0.72 and 0.78 at 105.0mm for the
      oblique length, 0.73 and 0.83 at 0.49 for the Agn-cdl to cdl-cdl ratio, and 0.82
      and 0.78 at 643 mm(2) for Deltaobl; the efficacy for females was greater in
      younger subjects. Although these parameters weakly depended on the body height
      (p<0.0001), the correlations were insufficient for stature estimation. These
      findings suggest the efficacy of CT morphometry of the mandible for sex
      discrimination with quantitative assessment.

PMID- 25595038
TI  - Bisubstrate inhibitor approach for targeting mitotic kinase Haspin.
AB  - During the past decade, the basophilic atypical kinase Haspin has emerged as a
      key player in mitosis responsible for phosphorylation of Thr3 residue of histone
      H3. Here, we report the construction of conjugates comprising an aromatic
      fragment targeted to the ATP-site of Haspin and a peptide mimicking the N
      terminus of histone H3. The combination of effective solid phase synthesis
      procedures and a high throughput binding/displacement assay with fluorescence
      anisotropy readout afforded the development of inhibitors with remarkable
      subnanomolar affinity toward Haspin. The selectivity profiles of novel conjugates
      were established by affinity studies with a model basophilic kinase (catalytic
      subunit of cAMP-dependent protein kinase) and by a commercial 1-point inhibition
      assay with 43 protein kinases.

PMID- 25595039
TI  - Abnormal morphology of myelin and axon pathology in murine models of multiple
      sclerosis.
AB  - Demyelination and axonal damage are responsible for neurological deficits in
      multiple sclerosis (MS), an inflammatory demyelinating disease of the central
      nervous system. However, the pathology of axonal damage in MS is not fully
      understood. In this study, histological analysis of morphological changes of
      axonal organelles during demyelination in murine models was investigated by
      scanning electron microscopy (SEM) using an osmium-maceration method. In
      cuprizone-induced demyelination, SEM showed typical morphology of demyelination
      in the corpus callosum of mouse brain. In contrast, SEM displayed variations in
      ultrastructural abnormalities of myelin structures and axonal organelles in
      spinal cord white matter of experimental autoimmune encephalomyelitis (EAE) mice,
      an animal model of MS. Myelin detachment and excessive myelin formation were
      observed as typical morphological myelin abnormalities in EAE. In addition, well
      developed axoplasmic reticulum-like structures and accumulated mitochondria were
      observed in tortuous degenerating/degenerated axons and the length of
      mitochondria in axons of EAE spinal cord was shorter compared with naive spinal
      cord. Immunohistochemistry also revealed dysfunction of mitochondrial
      fusion/fission machinery in EAE spinal cord axons. Moreover, the number of Y
      shaped mitochondria was significantly increased in axons of the EAE spinal cord.
      Axonal morphologies in myelin basic protein-deficient shiverer mice were similar
      to those in EAE. However, shiverer mice had "tortuous" (S-curve shaped
      mitochondria) and larger mitochondria compared with wild-type and EAE mice.
      Lastly, analysis of human MS patient autopsied brains also demonstrated abnormal
      myelin structures in demyelinating lesions. These results indicate that
      morphological abnormalities of myelin and axonal organelles play important role
      on the pathogenesis of axonal injury in demyelinating diseases. 

PMID- 25595040
TI  - Investigation of the functional properties and subcellular localization of alpha
      human and rainbow trout estrogen receptors within a unique yeast cellular
      context.
AB  - Estrogens are steroid hormones that play a pivotal role in growth,
      differentiation and function of reproductive and non-reproductive tissues,
      mediated through estrogen receptors (ERs). Estrogens are involved in different
      genomic and non-genomic cell signaling pathways which involve well-defined
      subcellular ER localizations. Thus, ER activity results from complex interplays
      between intrinsic binding properties and specific subcellular localization. Since
      these two factors are deeply intricate, we carried out, in a unique yeast cell
      context, a comparative study to better understand structure/function/subcellular
      distribution relationships. This was carried out by comparing two ERs: the human
      ER alpha subtype (hERalpha) and the short form of the alpha isoform of the
      rainbow trout ER (rtERalphaS). Their distinct binding properties to agonist and
      antagonist ligands and subcellular localizations were characterized in
      Saccharomyces cerevisiae yeast cells. An unexpected partial agonistic effect of
      ICI 182-780 was observed for rtERalphaS. Concomitant to distinct binding
      properties, distinct subcellular localizations were observed before and after
      ligand stimulation. Due to the unique cell context, the link between ERs
      intrinsic binding properties and subcellular localizations is partly unveiled and
      issues are hypothesized based on the role of cytoplasmic transient complexes
      which play a role in the ER cytoplasmic/nuclear partition, which in turn is
      critical for the recruitment of co-regulators in the nucleus. 

PMID- 25595041
TI  - Progesterone-induced stimulation of mammary tumorigenesis is due to the
      progesterone metabolite, 5alpha-dihydroprogesterone (5alphaP) and can be
      suppressed by the 5alpha-reductase inhibitor, finasteride.
AB  - Progesterone has long been linked to breast cancer but its actual role as a
      cancer promoter has remained in dispute. Previous in vitro studies have shown
      that progesterone is converted to 5alpha-dihydroprogesterone (5alphaP) in breast
      tissue and human breast cell lines by the action of 5alpha-reductase, and that
      5alphaP acts as a cancer-promoter hormone. Also studies with human breast cell
      lines in which the conversion of progesterone to 5alphaP is blocked by a 5alpha
      reductase inhibitor, have shown that the in vitro stimulation in cell
      proliferation with progesterone treatments are not due to progesterone itself but
      to the metabolite 5alphaP. No similar in vivo study has been previously reported.
      The objective of the current studies was to determine in an in vivo mouse model
      if the presumptive progesterone-induced mammary tumorigenesis is due to the
      progesterone metabolite, 5alphaP. BALB/c mice were challenged with C4HD murine
      mammary cells, which have been shown to form tumors when treated with
      progesterone or the progestin, medroxyprogesterone acetate. Cells and mice were
      treated with various doses and combinations of progesterone, 5alphaP and/or the
      5alpha-reductase inhibitor, finasteride, and the effects on cell proliferation
      and induction and growth of tumors were monitored. Hormone levels in serum and
      tumors were measured by specific RIA and ELISA tests. Proliferation of C4HD cells
      and induction and growth of tumors was stimulated by treatment with either
      progesterone or 5alphaP. The progesterone-induced stimulation was blocked by
      finasteride and reinstated by concomitant treatment with 5alphaP. The 5alphaP
      induced tumors expressed high levels of ER, PR and ErbB-2. Hormone measurements
      showed significantly higher levels of 5alphaP in serum from mice with tumors than
      from mice without tumors, regardless of treatments, and 5alphaP levels were
      significantly higher (about 4-fold) in tumors than in respective sera, while
      progesterone levels did not differ between the compartments. The results indicate
      that the stimulation of C4HD tumor growth in BALB/c mice treated with
      progesterone is due to the progesterone metabolite 5alphaP formed at elevated
      levels in mammary cells as a result of the 5alpha-reductase action on
      progesterone. The results provide the first in vivo demonstration that
      stimulation of breast cell tumorigenesis and tumor growth accompanying
      progesterone treatment is due to the progesterone metabolite 5alphaP, and that
      breast tumorigenesis can be blocked with the 5alpha-reductase inhibitor,
      finasteride. 

PMID- 25595042
TI  - Validated LC-MS/MS simultaneous assay of five sex steroid/neurosteroid-related
      sulfates in human serum.
AB  - Conventionally, the concentration of steroidal sulfates was estimated by indirect
      or immuno-based assays before the use of liquid-chromatography tandem mass
      spectrometry (LC-MS/MS). In the present study, a validated LC-MS/MS method is
      described for the simultaneous quantification of dehydroepiandrosterone sulfate
      (DHEA-S), estrone sulfate (E1-S), androsterone sulfate (ADT-S), pregnenolone
      sulfate (Preg-S) and allopregnanolone sulfate (Allopreg-S). E1-S binding to serum
      proteins was observed, especially for the high concentration quality control
      serum samples, leading to -10 to -15% bias using a polymer-based SPE. This
      protein binding can be efficiently eliminated using a Waters OasisTM WAX
      following the same extraction procedure. Most likely, the E1-S binding
      elimination on OasisTM WAX can be attributed to its different sorbent structure,
      where the benzeno group of E1-S can interact with the benzene of the backbone of
      OasisTM WAX. With this improvement, the method has been fully validated according
      to the FDA guidelines. The low quantification limits (LLOQs) are 40ng/mL,
      40pg/mL, 5ng/mL, 1.5ng/mL and 0.25ng/mL for DHEA-S, E1-S, ADT-S, Preg-S and
      Allopreg-S, respectively. A good linearity is obtained with R>0.99 for all
      compounds within the appropriate calibration range. Accuracies of all levels of
      QCs are within the range of 10% for DHEA-S, E1-S, ADT-S and Preg-S while for
      Allopreg-S, the accuracy is within the 15% range. The interday coefficient
      variance is 5.5-9.5% for the low limits of quantification of all five compounds
      while values of 1.3-9.9% are found for higher levels of QCs of all five
      compounds. Recovery of the five compounds in stripped serum is equivalent to that
      in unstripped serum. The average recovery difference is less than 5% between
      stripped and unstripped serum for each compound. All results of other test
      parameters such as matrix, hemolysis and lipemic effects as well as stabilities
      meet the acceptance criteria of EndoCeutics SOPs and FDA guidelines. 

PMID- 25595043
TI  - Characterisation and implementation of the ERE-CALUX bioassay on indoor dust
      samples of kindergartens to assess estrogenic potencies.
AB  - Estrogen-like endocrine disrupting chemicals (EEDCs) can be found abundantly in
      the environment. Due to their low-dose effects and the large amount of unknown
      EEDCs, it is difficult to assess and manage possible human health risks. For
      young children, who are particularly vulnerable to endocrine disruption due to
      their development rate, indoor dust is one of the main routes of exposure. In
      this study, an estrogen responsive elements chemically activated luciferase gene
      expression (ERE-CALUX) bioassay was characterized and implemented for the
      analysis of 12 dust samples from kindergartens in Flanders and Brussels
      (Belgium). The human ovarian carcinoma BG 1CALUX cell line showed reproducible
      results and a low limit of detection (LOD). The effective concentration at 50% of
      the maximum response (EC50) yielded 497 fg/well, while the LOD was 16 fg/well.
      For all dust samples, full dose-response curves and their corresponding EC50
      values could be calculated. All samples yielded bio-analytical equivalent
      concentrations (BEQs) that were significantly higher than the procedural blank
      level and ranged from 426 to 8710 pg E2 equivalents/g dust. A clear relationship
      was observed between a semi-quantitative interior score and the ERE-CALUX
      response of the samples. In addition, the concentration of phthalates, a major
      group of EEDCs used as plasticizers in plastics, was determined in the samples by
      GC-MS. Diisoheptyl phthalate (DiHP) and di(2-ethylhexyl) phthalate (DEHP) were
      present in every dust sample. A good correlation was found between ERE-CALUX
      activities and phthalate concentrations, when all phthalates except diisononyl
      phthalate (DiNP) and diisodecyl phthalate (DiDP), which do not bind to the
      estrogen receptor, were taken into account. This shows that the ERE-CALUX can
      provide relevant results concerning exposure to EEDCs from indoor dust. This
      article is part of a Special Issue entitled 'Endocrine disruptors & steroids'.

PMID- 25595044
TI  - Prevalence of Scedosporium species and Lomentospora prolificans in patients with
      cystic fibrosis in a multicenter trial by use of a selective medium.
AB  - OBJECTIVE: Detection of hyphomycetes of the Scedosporium apiospermum complex and
      Lomentospora prolificans (Sac-Lp) is not yet standardized. Prevalence rates in
      patients with cystic fibrosis (CF) and the resistance pattern of these pathogens
      in Germany are unknown. METHODS: In a one-year prospective study 11 laboratories
      used a selective medium for isolation of Sac-Lp, examining >11,600 respiratory
      samples from 2346 patients with CF. Isolates were identified by molecular methods
      and tested for susceptibility to antifungal drugs. RESULTS: The prevalence of Sac
      Lp in patients with CF in Germany varied from 0.0 to 10.5% (mean: 3.1%) among the
      clinical centres. The benefit of the selective medium SceSel(+) compared to
      standard media for fungi was documented for >5000 samples. High antifungal
      resistance was detected in the S. apiospermum complex, and the multiresistance of
      L. prolificans was confirmed. CONCLUSION: Microbiology laboratories should be
      aware of these resistant species in patients with CF and consider using a
      selective medium.

PMID- 25595045
TI  - Serum retinol levels and pulmonary function in children and adolescents with
      cystic fibrosis.
AB  - BACKGROUND: It has been suggested that higher serum retinol levels could have
      protective effects on pulmonary function (PF) in patients with cystic fibrosis
      (CF). However, serum retinol levels will be transiently decreased during
      pulmonary exacerbation. Therefore, the extent of chronic pulmonary inflammation
      should be included when describing the association between PF and serum retinol.
      We assessed the longitudinal relation between serum retinol, immunoglobulin G
      (IgG) and PF in paediatric CF patients. METHODS: We studied the serum retinol,
      IgG and forced expiratory volumes in one second (FEV(1)% pred.) of 228 CF
      patients during a seven-year follow up period. The cross-sectional and
      longitudinal relations between these variables were assessed. RESULTS: Serum
      retinol, with medians levels between 1.2 and 1.4 MUmol/l, were relatively stable,
      while median serum IgG gradually increased during the age years. The FEV(1)%
      pred. was longitudinally inversely associated with serum IgG and age, but not
      with serum retinol. Each g/l increase in serum IgG level was associated with an
      accelerated yearly decline in FEV(1)% pred. of 0.5% (95% CI -0.8 to -0.1,
      p=0.008), and each year increase in age was associated with a 1.7% (95% CI -2.1
      to -1.3, p=0.000) decline in FEV(1)% pred. This effect was not observed with
      respect to serum retinol levels (95% CI -1.9 to 2.2, p=0.570). CONCLUSIONS: In
      this large sample of children and adolescents with CF, we found no evidence that
      higher serum retinol levels had protective effects on PF.

PMID- 25595046
TI  - The relationship of anxiety, depression and behavioral problems with recurrent
      headache in late adolescence - a Young-HUNT follow-up study.
AB  - BACKGROUND: The comorbidity of headache and psychiatric symptoms is a well
      recognized clinical phenomenon, but there are only limited data regarding the
      temporal relationship between headache and symptoms of anxiety and depression as
      well as behavioral problems in adolescents. This study investigates the
      relationship of anxiety and depressive symptoms and behavioral problems at
      baseline with recurrent headache at follow-up four years later. METHODS: Within
      the Nord-Trondelag Health Study (HUNT), including repeated population-based
      studies conducted in Norway, 2399 adolescents in junior high schools aged 12-16
      years (77% of the invited) participated in Young-HUNT1 (1995-1997) and again at
      follow-up four years later, in Young-HUNT2 (2000-2001). The same comprehensive
      questionnaire that included assessment of symptoms of anxiety and depression and
      behavioral problems, i.e. conduct and attention difficulties was completed in
      both studies. In addition 1665 of the participants were interviewed about their
      headache complaints in Young-HUNT2. RESULTS: In adjusted multivariate analyses we
      found that higher scores of anxiety and depressive symptoms at baseline were
      associated with recurrent headache at follow-up four years later (OR: 1.6, 95%
      CI: 1.2-2.1, p = 0.001), evident for migraine (OR: 1.8, 95% CI: 1.2-2.7, p =
      0.008) and non-classifiable headache (OR: 1.7, 95% CI: 1.0-2.8, p = 0.034), but
      not statistically significant for tension-type headache (OR: 1.4, 95% CI: 1.0
      1.9, p = 0.053). Higher scores of anxiety and depressive symptoms at baseline
      were significantly associated with more frequent headache at follow-up (monthly
      vs. no recurrent headache OR: 1.8, 95% CI: 1.3-2.5, p = 0.001, weekly or daily
      vs. no recurrent headache OR: 1.9, 95% CI: 1.2-2.9, p = 0.005). Among adolescents
      without recurrent headache at baseline, higher scores for symptoms of anxiety and
      depression were associated with new onset migraine four years later (OR: 2.6, 95%
      CI: 1.1-4.8, p = 0.036). Higher scores of attention problems at baseline were
      associated with non-classifiable headache at follow-up (OR: 2.0, 95% CI: 1.3-3.4,
      p = 0.017). CONCLUSIONS: Results from the present study showed that symptoms of
      anxiety and depression in early adolescence were associated with recurrent
      headache four years later. Recognizing anxiety and depressive symptoms should be
      considered part of the clinical assessment in young headache patients, as early
      identification of these associated factors may lead to improved headache
      management.

PMID- 25595047
TI  - Is partial laryngectomy safe forever?
AB  - OBJECTIVES: Over past decades, function-preserving surgery has been oncologically
      effective for specific types of laryngeal cancer. Although safe short-term
      swallow function has been reported, swallow safety during long-term survival has
      received less attention. The purpose of this report is to highlight potential
      consequences of late dysphagia and chronic aspiration after partial laryngectomy.
      METHODS: A retrospective case series was performed. The head and neck cancer
      database from Yale-New Haven Hospital identified 3 patients requiring completion
      laryngectomy due to chronic aspiration 11-15 years after oncologically successful
      partial laryngectomy. Demographics, presentation, treatment, and course are
      included. RESULTS: Primary treatment was open supraglottic laryngectomy with
      adjuvant radiation therapy (n=2) and vertical hemilaryngectomy (n=1). All
      patients demonstrated locoregional control and preservation of swallow function
      for >10 years postoperatively. Due to late dysphagia and chronic aspiration, two
      patients required completion laryngectomy 11 and 15 years postoperatively and the
      third patient will require this 14 years postoperatively. CONCLUSIONS: Successful
      swallowing after function-preserving laryngeal surgery may not last forever
      despite adequate control of cancer. Three patients presented with aspiration 11
      15 years after partial laryngectomy and required definitive completion
      laryngectomy. This observation may affect preoperative counseling and
      consideration for longer post-operative follow-up. The data encourage a larger
      sample size.

PMID- 25595048
TI  - Recurrent squamous cell carcinoma of the temporal bone: critical analysis of
      cases with a poor prognosis.
AB  - PURPOSE: Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive
      malignancy with a significant recurrence rate. We reviewed our experience with
      recurrent TBSCCs. MATERIALS AND METHODS: Clinicopathological and therapeutic
      variables potentially associated with disease-free survival (DFS) and disease
      specific survival (DSS) were assessed in 17 TBSCC patients who died of their
      disease after treatment. RESULTS: TBSCC recurrences were treated with surgery in
      12 cases (palliative in 11, with curative intent in 1) and palliative
      chemotherapy in 5; the median DFS and DSS were 6 and 16 months, respectively. The
      mean DFS and DSS were longer in patients who had primary lateral temporal bone
      resection (LTBR) rather than subtotal temporal bone resection (STBR) (p=0.0173
      and p=0.03, respectively). Patients given non-surgical palliative treatment for
      recurrences had a longer mean DSS than those who underwent surgery (trend toward
      significance, p=0.09). CONCLUSIONS: Our results reflect the aggressive nature of
      TBSCC recurrences. Our findings seem to support the use of non-surgical
      treatments (chemotherapy, radiotherapy, or specialist palliative care) in
      patients with loco-regionally advanced recurrent TBSCC. Salvage surgery might be
      considered for early recurrences when radicality is still achievable. Precise
      guidelines for the rational follow-up of surgically-treated TBSCCs need to be
      shared between tertiary centers.

PMID- 25595049
TI  - Phantom study of an ultrasound guidance system for transcatheter aortic valve
      implantation.
AB  - A guidance system using transesophageal echocardiography and magnetic tracking is
      presented which avoids the use of nephrotoxic contrast agents and ionizing
      radiation required for traditional fluoroscopically guided procedures. The aortic
      valve is identified in tracked biplane transesophageal echocardiography and used
      to guide stent deployment in a mixed reality environment. Additionally, a
      transapical delivery tool with intracardiac echocardiography capable of
      monitoring stent deployment was created. This system resulted in a deployment
      depth error of 3.4mm in a phantom. This was further improved to 2.3mm with the
      custom-made delivery tool. In comparison, the variability in deployment depth for
      traditional fluoroscopic guidance was estimated at 3.4mm.

PMID- 25595050
TI  - Development and application of biological technologies in fish genetic breeding.
AB  - Fish genetic breeding is a process that remolds heritable traits to obtain
      neotype and improved varieties. For the purpose of genetic improvement,
      researchers can select for desirable genetic traits, integrate a suite of traits
      from different donors, or alter the innate genetic traits of a species. These
      improved varieties have, in many cases, facilitated the development of the
      aquaculture industry by lowering costs and increasing both quality and yield. In
      this review, we present the pertinent literatures and summarize the biological
      bases and application of selection breeding technologies (containing traditional
      selective breeding, molecular marker-assisted breeding, genome-wide selective
      breeding and breeding by controlling single-sex groups), integration breeding
      technologies (containing cross breeding, nuclear transplantation, germline stem
      cells and germ cells transplantation, artificial gynogenesis, artificial
      androgenesis and polyploid breeding) and modification breeding technologies
      (represented by transgenic breeding) in fish genetic breeding. Additionally, we
      discuss the progress our laboratory has made in the field of chromosomal ploidy
      breeding of fish, including distant hybridization, gynogenesis, and androgenesis.
      Finally, we systematically summarize the research status and known problems
      associated with each technology. 

PMID- 25595051
TI  - The hypoxia signaling pathway and hypoxic adaptation in fishes.
AB  - The hypoxia signaling pathway is an evolutionarily conserved cellular signaling
      pathway present in animals ranging from Caenorhabditis elegans to mammals. The
      pathway is crucial for oxygen homeostasis maintenance. Hypoxia-inducible factors
      (HIF-1alpha and HIF-2alpha) are master regulators in the hypoxia signaling
      pathway. Oxygen concentrations vary a lot in the aquatic environment. To deal
      with this, fishes have adapted and developed varying strategies for living in
      hypoxic conditions. Investigations into the strategies and mechanisms of hypoxia
      adaptation in fishes will allow us to understand fish speciation and breed
      hypoxia-tolerant fish species/strains. This review summarizes the process of the
      hypoxia signaling pathway and its regulation, as well as the mechanism of hypoxia
      adaptation in fishes. 

PMID- 25595053
TI  - Brief overdose education is sufficient for naloxone distribution to opioid users.
AB  - BACKGROUND: While drug users are frequently equipped with naloxone for lay opioid
      overdose reversal, the amount of education needed to ensure knowledge of
      indications and administration is unknown. METHODS: We administered four
      instruments, assessing comfort and knowledge around opioid overdose and naloxone
      administration, to opioid users receiving naloxone for the first time (N=60) and
      upon returning for a refill (N=54) at community distribution programs.
      Participants completed the instruments prior to receiving naloxone; first-time
      recipients repeated the instruments immediately after the standardized 5-10min
      education. RESULTS: Comfort with recognition of, response to, and administration
      of naloxone for an overdose event significantly increased after brief education
      among first-time recipients (p<0.05). Knowledge of appropriate responses to
      opioid overdose was high across all assessments; 96% of participants could
      identify at least one acceptable action to assess and one acceptable action to
      care for an opioid overdose. Facility with naloxone administration was high
      across all assessments and significantly increased for intranasal administration
      after education for first-time recipients (p<0.001). First-time recipients
      (before and after education) and refillers demonstrated a high level of knowledge
      on the Brief Overdose Recognition and Response Assessment, correctly identifying
      a mean of 13.7 out of 16 overdose scenarios. CONCLUSIONS: Opioid users seeking
      naloxone in San Francisco have a high level of baseline knowledge around
      recognizing and responding to opioid overdose and those returning for refills
      retain that knowledge. Brief education is sufficient to improve comfort and
      facility in recognizing and managing overdose.

PMID- 25595052
TI  - The Alcohol Use Disorder and Associated Disabilities Interview Schedule-5
      (AUDADIS-5): reliability of substance use and psychiatric disorder modules in a
      general population sample.
AB  - BACKGROUND: The purpose of this study was to assess the test-retest reliability
      of substance use disorder and psychiatric modules in the Alcohol Use Disorder and
      Associated Disabilities Interview Schedule, Diagnostic and Statistical Manual of
      Mental Disorders, Fifth Edition (DSM-5) Version (AUDADIS-5). METHODS: Kappa and
      intraclass correlation coefficients were calculated for DSM-5 substance use and
      psychiatric disorder diagnoses and dimensional criteria scales using a test
      retest design among 1006 respondents drawn from the National Epidemiologic Survey
      on Alcohol and Related Conditions-III (NESARC-III). RESULTS: Reliabilities of
      substance use disorder diagnoses and associated criteria scales were generally
      good to excellent, while reliabilities for mood, anxiety and trauma and stress
      related disorders and associated scales were generally in the fair to good range.
      CONCLUSIONS: The observed reliability of the DSM-5 diagnoses and dimensional
      scales for the substance use and psychiatric disorders found in this study
      indicates that the AUDADIS-5 can be a useful tool in various research settings,
      particularly in studies of the general population, the target population for
      which it was designed.

PMID- 25595056
TI  - Multiple linear regression solvatochromic analysis of donar-acceptor imidazole
      derivatives.
AB  - Catalytic synthesis of some polysubstituted imidazoles under solvent-free
      condition is reported and their characterization has been carried out spectral
      techniques. Electronic spectral studies reveal that their solvatochromic behavior
      depends both the polarity of the medium and hydrogen bonding properties of the
      solvents. Specific hydrogen bonding interaction in polar solvents modulated the
      order of the two close lying lowest singlet states. The solvent effect on
      absorption and emission spectral results has been analyzed by multiple parametric
      regression analysis. Solvatochromic effects on the emission spectral position
      indicate the charge transfer (CT) character of the emitting singlet states both
      in a polar and a non polar environment. The fluorescence decays for the
      imidazoles fit satisfactorily to a bi exponential kinetics. These observations
      are in consistent with quantum chemical calculations. 

PMID- 25595055
TI  - Estradiol rapidly modulates synaptic plasticity of hippocampal neurons:
      Involvement of kinase networks.
AB  - Estradiol (E2) is locally synthesized within the hippocampus in addition to the
      gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential
      for synaptic regulation. Molecular mechanisms of modulation through synaptic
      estrogen receptor (ER) and its downstream signaling, however, have been still
      unknown. We investigated induction of LTP by the presence of E2 upon weak theta
      burst stimulation (weak-TBS) in CA1 region of adult male hippocampus. Since only
      weak-TBS did not induce full-LTP, weak-TBS was sub-threshold stimulation. We
      observed LTP induction by the presence of E2, after incubation of hippocampal
      slices with 10nM E2 for 30 min, upon weak-TBS. This E2-induced LTP was blocked by
      ICI, an ER antagonist. This E2-LTP induction was inhibited by blocking Erk MAPK,
      PKA, PKC, PI3K, NR2B and CaMKII, individually, suggesting that Erk MAPK, PKA,
      PKC, PI3K and CaMKII may be involved in downstream signaling for activation of
      NMDA receptors. Interestingly, dihydrotestosterone suppressed the E2-LTP. We also
      investigated rapid changes of dendritic spines (=postsynapses) in response to E2,
      using hippocampal slices from adult male rats. We found 1nM E2 increased the
      density of spines by approximately 1.3-fold within 2h by imaging Lucifer Yellow
      injected CA1 pyramidal neurons. The E2-induced spine increase was blocked by ICI.
      The increase in spines was suppressed by blocking PI3K, Erk MAPK, p38 MAPK, PKA,
      PKC, LIMK, CaMKII or calcineurin, individually. On the other hand, blocking JNK
      did not inhibit the E2-induced spine increase. Taken together, these results
      suggest that E2 rapidly induced LTP and also increased the spine density through
      kinase networks that are driven by synaptic ER. This article is part of a Special
      Issue entitled SI: Brain and Memory.

PMID- 25595054
TI  - Effects of marijuana use on impulsivity and hostility in daily life.
AB  - BACKGROUND: Marijuana use is increasingly prevalent among young adults. While
      research has found adverse effects associated with marijuana use within
      experimentally controlled laboratory settings, it is unclear how recreational
      marijuana use affects day-to-day experiences in users. The present study sought
      to examine the effects of marijuana use on within-person changes in impulsivity
      and interpersonal hostility in daily life using smartphone administered
      assessments. METHODS: Forty-three participants with no substance dependence
      reported on their alcohol consumption, tobacco use, recreational marijuana use,
      impulsivity, and interpersonal hostility over the course of 14 days. Responses
      were analyzed using multilevel modeling. RESULTS: Marijuana use was associated
      with increased impulsivity on the same day and the following day relative to days
      when marijuana was not used, independent of alcohol use. Marijuana was also
      associated with increased hostile behaviors and perceptions of hostility in
      others on the same day when compared to days when marijuana was not used. These
      effects were independent of frequency of marijuana use or alcohol use. There were
      no significant effects of alcohol consumption on impulsivity or interpersonal
      hostility. CONCLUSIONS: Marijuana use is associated with changes in impulse
      control and hostility in daily life. This may be one route by which deleterious
      effects of marijuana are observed for mental health and psychosocial functioning.
      Given the increasing prevalence of recreational marijuana use and the potential
      legalization in some states, further research on the potential consequences of
      marijuana use in young adults' day-to-day life is warranted.

PMID- 25595058
TI  - Synthesis, characterization and photophysical properties of novel azole
      derivatives.
AB  - This paper concerns the design, synthesis, structural characterization, thermal
      stability evaluation and fluorescence properties of novel triazolothiadiazole
      derivatives. The target compounds 6a-e were synthesized by condensing 4-amino-3
      (4-methoxybenzyl)-1H-1,2,4-triazole-5 (4H)-thione (5) with biphenyl, naphthyl, p
      terphenyl, pyrenyl and ferrocenyl carboxylic acid in the presence of phosphorous
      oxychloride. The structures of newly synthesized compounds were characterized by
      IR, (1)H NMR and (13)C NMR analysis. The photophysical properties of synthesized
      compounds were measured in a variety of organic solvents of variable polarities.
      Spectral properties of the compounds were highly dependent on the nature of the
      substituent and coupling components attached to the triazolothiadiazole skeleton
      as well as slightly affected by the solvent polarities. Correlation of the
      absorption spectra and fluorescence emission response of 6a-e with the
      substituent revealed that the fluorescent properties can easily be tuned by
      varying conjugation length of side coupled groups. The newly synthesized
      derivatives represent a new type of fluorescent materials with efficient visible
      absorption and surpassing brightness which could be a promising candidate for
      bioimaging, photonic applications, organic light emitting diodes and dye
      sensitized solar cells.

PMID- 25595057
TI  - Membrane effects of N-terminal fragment of apolipoprotein A-I: a fluorescent
      probe study.
AB  - The binding of monomeric and aggregated variants of 1-83 N-terminal fragment of
      apolipoprotein A-I with substitution mutations G26R, G26R/W@8, G26R/W@50 and
      G26R/W@72 to the model lipid membranes composed of phosphatidylcholine and its
      mixture with cholesterol has been investigated using fluorescent probes pyrene
      and Laurdan. Examination of pyrene spectral behavior did not reveal any marked
      influence of apoA-I mutants on the hydrocarbon region of lipid bilayer. In
      contrast, probing the membrane effects by Laurdan revealed decrease in the probe
      generalized polarization in the presence of aggregated proteins. suggesting that
      oligomeric and fibrillar apoA-I species induce increase in hydration degree and
      reduction of lipid packing density in the membrane interfacial region. These
      findings may shed light on molecular details of amyloid cytotoxicity. 

PMID- 25595059
TI  - Fluorescence spectroscopy as a tool for determination of coumarins by
      multivariate calibration.
AB  - At present, it is necessary to check the quality of many food products in which
      the content of coumarins is limited. Since a rapid and simple method for the
      determination of coumarin (COU), 4-hydroxycoumarin (4HC) and dicoumarol (DC) in
      tea samples was needed, we developed an alternative option to chromatography,
      i.e., fluorescence spectroscopy with multivariate calibration. The synchronous
      fluorescence spectra were recorded at constant wavelength differences 70, 80 and
      90 nm from 200 to 400 nm. The different experimental parameters affecting the
      synchronous fluorescence intensities of the analytes were carefully studied and
      optimized. Partial least squares (PLS) method and multi linear regression (MLR)
      were compared on determining the concentrations. The best results were obtained
      by the PLS method on synchronous fluorescence spectra at Deltalambda = 90 nm. The
      results from the analysis of herbal tea Melilotus officinalis by synchronous
      fluorescence spectroscopy with PLS model are equivalent with the results from
      HPLC. Fisher F-test and Student's t-test confirmed this finding.

PMID- 25595060
TI  - Malignant rhabdoid transformation of a longstanding, aggressive, and recurrent
      orbital angiomyxoma.
AB  - A 47-year-old woman presented with a medial orbital tumor initially diagnosed as
      either a myxoid neurofibroma or myoepithelioma. Over 30 years the tumor recurred
      seven times and was serially debulked. Careful histopathologic analysis coupled
      with immunohistochemical studies performed on the last two biopsies established
      the rare diagnosis of a locally aggressive angiomyxoma (because of its local
      infiltrative growth) with myofibroblastic features (smooth muscle actin and
      calponin positivity and desmin negativity). The last recurrence manifested at a
      shorter interval than the earlier ones, suggesting an accelerating clinical
      course. By this late stage there was complete blindness, a frozen globe, and
      extreme, unmeasurable proptosis accompanied by massive chemosis and eyelid
      fullness. An exenteration was performed, and the orbital contents contained a
      persistent angiomyxoma, but additionally, another cellular population had emerged
      mitotically active cells with a malignant rhabdoid phenotype (round shape,
      cytoplasmic hyaline/globoid inclusions composed of whorls of compact vimentin
      filaments as well as epithelial membrane antigen and focal cytokeratin
      positivity). This is the first orbital case of a rhabdoid transformation of a
      benign orbital mesenchymal tumor. Shortly after the exenteration, multifocal
      metastases, notably to the lungs, were found, leading to the introduction of
      chemotherapy, which was discontinued because of non-responsiveness of the tumor
      and patient intolerance. After 1 year of follow up, the patient is still alive,
      but has persistent active disease with widespread metastases and a guarded
      prognosis. 

PMID- 25595062
TI  - Bowel preparation before colonoscopy.

PMID- 25595061
TI  - Optic nerve lymphoma: report of two cases and review of the literature.
AB  - Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in
      association with central nervous system (CNS) or systemic lymphoma. We present
      two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our
      findings with previously reported cases. We discuss the mechanism of metastasis,
      classification of optic nerve involvement, clinical features, radiologic
      findings, optic nerve biopsy indications and techniques, histologic features, and
      treatments. We propose a classification system of optic nerve lymphoma: isolated
      optic nerve involvement, optic nerve involvement with CNS disease, optic nerve
      involvement with systemic disease, and optic nerve involvement with primary
      intraocular lymphoma. Although it is an uncommon cause of infiltrative optic
      neuropathy, optic nerve metastasis should be considered in patients with a
      history of lymphoma. The recommended approach to a patient with presumed optic
      nerve lymphoma includes neuroimaging and cerebrospinal fluid evaluation as part
      of the initial workup, then judicious use of optic nerve biopsy, depending on the
      clinical situation. 

PMID- 25595063
TI  - Drivers of facility deliveries in Africa and Asia: regional analyses using the
      demographic and health surveys.
AB  - BACKGROUND: In the past few decades many countries have worked to increase the
      number of women delivering in facilities, with the goal of improving maternal and
      neonatal health outcomes. The purpose of this study is to explore the current
      situation of facility deliveries in Africa and Asia to understand where and with
      whom women deliver. Furthermore, we aim to test potential drivers of facility
      delivery at the individual, household, and community-level. METHODS: Demographic
      and Health Survey data collected since 2003 from 43 countries in Africa and Asia
      is explored to understand the patterns of where women are delivering. We look at
      patterns by region and wealth quintile and urban/rural status. We then run a
      series of multi-level models looking at relationships between individual,
      household and community-level factors and the odds of a woman delivering in a
      facility. We explore this for Asia and Africa separately. We also look at
      correlates of delivery with a trained provider, in a public facility, in a
      private facility, with a doctor and in a hospital. RESULTS: The majority of women
      deliver in a facility and with a provider; however, about 20% of deliveries are
      still with no one or a friend/relative or alone. Rates of facility delivery are
      lower in Asia overall, and a greater proportion of deliveries take place in
      private facilities in Asia compared to Africa. Most of the individual level
      factors that have been found in past studies to be associated with delivering in
      a facility hold true for the multi-country-level analyses, and small differences
      exist between Asia and Africa. Women who deliver in private facilities differ
      from women who deliver in public facilities or at home. CONCLUSIONS: Most women
      in Africa and Asia are delivering in a facility, and drivers of facility delivery
      identified in smaller level or country specific studies hold true in multi
      country national level data. More data and research is needed on other drivers,
      especially at the country-level and relating to the quality of care and maternal
      health complications.

PMID- 25595065
TI  - [Acute hospital collaboration with the region].
AB  - The palliative care team of Tokai University Hospital began its activities in
      2004. After several changes in its organization, the activities of the palliative
      care team have become well known, and this department has become very active.
      Palliative care at our hospital has now broadened its scope and now includes both
      inpatients and outpatients. Initially, the patients primarily consisted of
      terminal-stage cancer patients, but in recent years patients who are being
      treated for cancer have also been included in the palliative care department. In
      terms of our collaboration with the region, the health care providers responsible
      for palliative care are making continued efforts to establish good relationships
      through regular scheduled palliative care training workshops and study sessions.
      Regional collaborations with oncologists is the ultimate/primary goal. As an
      educational institution we conduct clinical practical training and clinical
      training in core hospitals and private practices with medical students and junior
      resident physicians. However, few of these training institutions are home-care
      supporting clinics or home-care-supporting hospitals. It remains unclear whether
      medical students and resident physicians are involved in home care. Knowledge of
      palliative care has gradually increased among the health care providers at our
      hospital. However, the dissemination of knowledge about home care among medical
      students, resident physicians, and oncologists is found to be lacking; hence, we
      have made this our goal. Another goal of ours would be to train existing
      physicians to equip them with knowledge and experience necessary for dealing with
      home care. 

PMID- 25595064
TI  - Safety Study of Transcranial Static Magnetic Field Stimulation (tSMS) of the
      Human Cortex.
AB  - BACKGROUND: Transcranial static magnetic field stimulation (tSMS) in humans
      reduces cortical excitability. OBJECTIVE: The objective of this study was to
      determine if prolonged tSMS (2 h) could be delivered safely in humans. Safety
      limits for this technique have not been described. METHODS: tSMS was applied for
      2 h with a cylindric magnet on the occiput of 17 healthy subjects. We assessed
      tSMS-related safety aspects at tissue level by measuring levels of neuron
      specific enolase (NSE, a marker of neuronal damage) and S100 (a marker of glial
      reactivity and damage). We also included an evaluation of cognitive side effects
      by using a battery of visuomotor and cognitive tests. RESULTS: tSMS did not
      induce any significant increase in NSE or S100. No cognitive alteration was
      detected. CONCLUSIONS: Our data indicate that the application of tSMS is safe in
      healthy human subjects, at least within these parameters.

PMID- 25595066
TI  - [An examination of home care for patients over age 85 after surgery].
AB  - To examine home care for patients over age 85 after surgery, we made comparisons
      across postoperative courses for their effects on disuse syndrome based on the
      duration of home care and the duration of survival. The duration of home care was
      long in surgical cases of patients aged under 74 and patients aged 75-84, and it
      was short in surgical cases of patients aged over 85. Although having trust in
      surgeons may delay the transition to home care, early transition is desirable. In
      terms of the duration of survival, surgery was effective for patients aged under
      74 and 75-84, but no difference was noted between patients aged over 85 who had
      undergone surgical intervention and those who had undergone conservative
      intervention, showing that surgeries have little effect on prolonging the life of
      patients aged over 85. Some patients aged over 85 may become bedridden as a
      result of surgery. There are certainly needs for welfare facilities equipped with
      medical services and other such measures for those who cannot be cared for at
      home, but undergoing conservative treatment through integrated community care is
      also considered an option. 

PMID- 25595067
TI  - [Current situation of available back-up beds for terminal home care patients].
AB  - The Palliative Care Unit at Heiwa Hospital has 16 beds, and offers inpatient
      support in general wards, as well as back-up beds in emergencies in collaboration
      with local home care support clinics. For two years from January 2012 to December
      2013, there were 1,213 cases where patients were seen for initial outpatient
      visits at the Department of Palliative Care. At the time of the initial visit,
      visiting medical care had been introduced for 25% of the cases. Although 59% of
      the patients who visited our department are hospitalized, 20% of inpatients have
      been hospitalized at the request of their home care physician. The availability
      of back-upbeds offers patients and their families, as well as related medical
      institutions, a sense of security, and enables home care to continue. The
      significance of back-upbeds will become even more important in the future. 

PMID- 25595068
TI  - [Present status of regional collaboration of home care medicine at Kohka Medical
      County(Kohka-City and Konan-City), Shiga prefecture].
AB  - The importance of home care medicine has been well recognized by the National and
      Prefectural policy. We have conducted several meetings on home care medicine and
      discussed various problems and barriers that need to be overcome. These meetings
      were held with various professionals. The meetings, however, were conducted with
      little communication between professionals, especially regarding cancer and non
      cancerous lesions. The members who perform the home care medicine are the same
      persons regardless of the regions they are from. We are, therefore, trying to
      improve the communication between these professionals in order to consolidate
      these meetings. We have recognized and understand the present status of home care
      medicine through these meetings and are willing to make efforts to improve the
      home medical practice and care. 

PMID- 25595070
TI  - [Support for cancer caregivers during the palliative, hospice, and bereavement
      phases: the role of family physicians].
AB  - The family caregivers of cancer patients are at an increased risk of physical and
      mental morbidity. The purpose of this study is to capture the needs of the
      caregivers before and during the years after the loss of the patient. A survey
      was conducted among 229 consecutive advanced cancer patients in our family
      clinic. Seventy percent of the patients died in their homes, the median overall
      survival was 15.1 months, and the median survival time was 3 months from the
      beginning of the coordination with oncologists. While 28%of the patients received
      the best possible supportive care alone and 50%of them were admitted after the
      cessation of chemotherapy, in 22%of the patients, the coordination with
      oncologists began during the chemotherapy phase. During times of active cancer
      treatment, the caregivers were provided with various types of support from the
      family physicians. In the post-death bereavement phase, 124 caregivers were
      admitted to our family care clinic. The family physician can play an important
      role in aiding the caregivers during the palliative, hospice, and bereavement
      phases. 

PMID- 25595069
TI  - [Leadership in the promotion of inter-professional collaboration in terminal
      cancer care].
AB  - Home care requires indispensable inter-professional/inter-organizational
      collaboration. However, due to differences in specialization, the language used,
      and work structure, medical professionals may be confronted with a gap between
      the ideal and reality of collaboration. In the present case, a 50-year-old female
      with terminal cancer wished to receive home care and was consequently transferred
      to her home. The patient has been receiving a 24-h continuous drip infusion via a
      central venous route and using a patient-controlled analgesia pump for pain
      management. She has chronic respiratory failure in addition to cancer-related
      pain. Furthermore, she has been injecting herself with insulin 4 times per day
      because she has type 2 diabetes. The patient requires almost full assistance in
      daily life. This type of home care is equivalent to inpatient care that requires
      inter-professional and inter-organizational collaboration by 12 professionals.
      The leadership of a care manager with knowledge of a patient's life and family
      background is essential in such cases. 

PMID- 25595071
TI  - [Barriers upon providing assistance and making arrangements for being discharged
      from hospital and changing hospitals while undergoing cancer therapy - when in a
      state of depression (from the perspective of a psycho-oncologist) - part 5].
AB  - In the final stages of cancer, home care becomes difficult because the patients
      face reduced physical strength and energy, people around them have physical and
      mental fatigue, and available medical treatment options are exhausted. Although
      there are many underlying factors, prolonged depression is also mentioned as a
      cause of the difficulties of home care. This paper reports on one case in which
      we reaffirmed the most important factor of homecare - preventing a feeling of
      isolation for patients who wish to stay at home even if they are experiencing
      depression. Following in the steps of the many major hospitals that coordinate
      cancer treatment, we have posted multi-disciplinary staff at our Cancer
      Consultation Support Center and the Cancer Palliative Care Team to support a
      patient's lifestyle at home as long as possible even in the terminal stages of
      cancer with repeated shared decision-making with the patient and his/her family
      members. 

PMID- 25595072
TI  - [Decision making support for chemotherapy outpatients and their families: role of
      the home care professional].
AB  - The intervention of palliative care from the early stages of cancer is advocated,
      however, current situation remains virtually unchanged. Since the Baptist Home
      Hospice Palliative Care Clinic opened, the percentage of patients who have been
      introduced to the clinic during chemotherapy and have received home-visit care is
      16.1%. Of those, the percentage of patients who passed away more than two months
      since the start of home-visit care is 45.7%. We determine the direction in care
      by listening closely to our patients and their families, and putting advance care
      planning (ACP) into effect. One of our roles is to offer support in deciding to
      discontinue the treatment in the final stages of chemotherapy. It is recognized
      that a number of patients are undergoing ineffective chemotherapy, despite the
      strong side effects. Our clinic strives to help these patients spend time the way
      they want by providing home-visit care and home-visit nursing.

PMID- 25595074
TI  - [Effective methods of organizing complex information in advanced cancer
      patients].
AB  - Advanced cancer patients often present with variable clinical information
      documenting widespread lesions and treatment histories. For health care
      providers, organizing and managing this information is crucial. In our ambulatory
      and home palliative/ hospice care practice, two visual tools are used: 1 ) a one
      page line diagram which shows the Edmonton Labeled Visual Information System
      (ELVIS) and a schematic demarcation of dermatomes shown as distinct segments, and
      2 ) a one-page summary report containing various graphs displaying the transition
      of clinical variables which appear to be predictive of survival. These concise
      visual representations of cancer information can be beneficial for summarizing or
      reviewing the disease and its clinical course, and in the transfer of patient
      information to other institutions. They may also serve as an aid to improve
      information recall in cancer patients, as well as to provide both the patients
      and their caregivers with information about cancer trajectories so that they can
      set appropriate goals, priorities, and expectations of care.

PMID- 25595073
TI  - [Home care for terminal cancer patients from the family and caregiver
      perspective].
AB  - The progression of home care provision is associated with an increased burden on
      the family, as patients tend to progressively become more dependent on medicine.
      In the present case, a family supported a patient by performing medical
      activities such as taking blood sugar measurements, administering insulin
      injections, exchanging fluids, managing each tube, handling medical devices,
      conducting status observations, and attending to emergency calls. Thus, the
      family caregiver undertakes duties that were previously performed by a nurse and
      interacts with the various professionals who visit the patient's home daily.
      Therefore, the caregiver undergoes a considerable amount of stress. Family
      caregivers with no medical knowledge or nursing experience require plenty of
      support, in order to fulfill a patient's requirements. The first step is the
      establishment of trust between the medical professionals and the caregiver. In
      the present case, because the trust had been established, interprofessional
      collaboration ensured that the patient received support until the end. Thus, we
      reported on the perspectives of the family and caregiver on home care for
      terminal cancer patients.

PMID- 25595075
TI  - [Supervised administration of Alzheimer's patients using information
      communication technology].
AB  - Drug adherence is central to the treatment of dementia, which might reduce
      compliance due to memory loss, particularly among home-based patients with
      dementia. In order to improve drug adherence, we suggest the efficient and
      effective supervised administration by use of information communication
      technology(ICT). ICT makes face-to-face real-time communication possible, and it
      also enables picture sharing. Therefore, it might be useful to apply ICT to
      controlling and supervising medication for patients with dementia to improve drug
      adherence. Accordingly, we enrolled patients who were supposed to take a newly
      prescribed anti-dementia patch containing the choline esterase inhibitor
      rivastigmine(Rivastach(r))and investigated the effect of ICT-based intervention
      for drug adherence, emotional change, and cognitive change, utilizing Skype, a
      free communication software program. Scheduled Skype interventions increased drug
      adherence ratio, levels of subjective satisfaction, and instrumental activities
      of daily living(IADL). Furthermore, we can provide patients and their caregivers
      with a feeling of safety through regular bidirectional communication, as patients
      can easily consult medical staff regarding the adverse effects of newly
      prescribed drugs. Instead of frequent visits to their primary physicians, ICT
      based communications can be used as a substitute for supervision of medication,
      given the availability of the telecommunication system. By directly connecting
      the medical institution to the home, we expect that this ICT-based system will
      expand into the geriatric care field, including the care of elderly individuals
      living alone. 

PMID- 25595076
TI  - [At-home music therapy intervention using video phone (Skype) for elderly people
      with dementia].
AB  - There are various nonpharmacological therapies available for elderly people with
      dementia, and these can improve quality of life and the behavioral and
      psychological symptoms of dementia (BPSD) that appear throughout the progression
      of the disease. Since a substantial number of effects have been reported for
      music therapy, we focused on this nonpharmacological intervention. Generally,
      musical therapy is provided collectively in facilities. However, the music used
      in this context may not consider the preferences and music abilities of each
      person. Therefore, in this study we created made-to-order music CDs that
      accounted for each participant's musical preferences and abilities. Utilizing the
      CDs, we conducted an intervention study of music therapy using a video phone
      (Skype) that elderly people with dementia can use at home. An advantage of
      conducting music therapy for individuals with dementia using a video phone is
      that those who have difficulty going to the hospital or participating in dementia
      related therapy groups can participate in therapy in a familiar place. The
      results of this intervention showed that participants demonstrated signs of
      improvement as measured by the smile degree(Smile scan)and Behavior Pathology in
      Alzheimer's Disease (BEHAVE-AD) scale.

PMID- 25595077
TI  - [Conduct of survey four months after the start of EMR for home visits to promote
      cooperation between hospitals and clinics].
AB  - Electronic medical records(EMR)for home visits were introduced in October 2013 at
      our institution in order to ensure smooth cooperation between the hospital and
      clinic by sharing the details of a patient's medical record. A system was
      developed for remote desktop connections to the EMR terminal server(virtual
      server)with the use of an SSL-VPN. Mobile terminals and mobile printers were
      used. Four months after the start of this system, a survey was conducted for 41
      home care professionals and other staff(physicians, nurses, and office staff).
      Home care staff indicated that they had problems with the system, including bad
      connections and operating conditions, and difficulties responding to problems
      when they arose. Other staff indicated that they were able to acquire patient
      information faster than with paper-based records. Future issues include
      improvements to the user-friendliness of the terminals and improved responses to
      problems when they occur. 

PMID- 25595078
TI  - [A study of the usefulness of shared decision making during medical treatment and
      care-giving in home care].
AB  - Forty patients who made a decision about home-based care among 65 deaths from
      November 2012 to December 2013(21 men, 19 women, average age: 83 years)were
      evaluated. The family had already decided upon home caregiving in six of these
      cases. We conducted a clinical ethics dialogue on performing caregiving at home
      or introducing home care for 34 cases. However, many differences were found in
      the description of the contents of the medical side of home care and the concept
      of patients and families in six cases of those 34 cases. It was difficult to
      conduct the clinical ethics dialogue in such cases. We also incorporated a shared
      decision making method in order to overcome differences in the way of thinking of
      these cases. As a result, patients and their families came to voluntarily receive
      home care and caregiving at home. Thus, shared decision making was a useful
      method in home care. 

PMID- 25595079
TI  - ["Manual on physician behavior at the time of death certification" created
      through collaboration with different local healthcare workers].
AB  - It is thought that physicians' behavior at the scene of death certification has a
      considerable influence on the grief of the bereaved. We constructed a manual to
      guide the physician's behavior at death certification and educate residents and
      medical students. We collaborated locally across several occupations(e.g.,
      visiting nurse, visiting pharmacist)for the purpose of upgrading the manual. We
      conducted interviews with physicians and nurses who perform home medical care in
      this area regarding the scene at a real death certification in making our manual.
      It was evaluated well in this trial, and participants were cooperative with the
      interview. We can conduct many collaborations locally in various forms. The
      regional alliances become smoother as a function of such collaborations. In
      addition, it is thought that the manual that was constructed following this
      process will be easily received in the area. 

PMID- 25595080
TI  - [Dementia tends to become an impediment to continued homecare - "staying home
      until death" even with dementia].
AB  - With the rate of aging rising each year, the number of patients with dementia
      increases. The latest study released by the Ministry of Health, Labour and
      Welfare estimated that, as of 2012, there were a total of 3.05 million people
      with dementia in Japan, with 10% of aged 65 and over, 15% of aged 70 and over,
      20% of aged 75 and over, and 40% of aged 85 and over. Dementia includes
      Alzheimer's disease, which makes up the most cases, dementia with Lewy bodies,
      frontotemporal dementia, and cerebrovascular dementia which is caused by a
      cerebral infarction or cerebral hemorrhage. Hypothyroidism, normal pressure
      hydrocephalus, and depression also impair cognitive functions, and therefore
      these pathological conditions are easily mistaken for dementia. Methods that can
      easily distinguish between these diseases have been devised. Early and accurate
      diagnoses are very important for patients and their families as there are a
      number of diseases that can be treated. In addition, although Japan only has
      medicines that delay the advance of Alzheimer's disease, in recent years, efforts
      have been made to prevent the onset of Alzheimer's disease through reducing the
      potential for diabetes, high blood pressure, obesity, and depression, quitting
      smoking, and improving physical and intellectual activities. At the annual
      meeting last year, we reported the results of a survey at our health counseling
      center on the quality of life a person wants as dementia progresses. The survey
      had some surprising results: two-thirds of the people surveyed preferred to be in
      a group home or an advanced medical center, rather than in their own homes. One
      third of the respondents expressed a desire to be at home. The survey showed that
      if possible, a person diagnosed with dementia will stay at home, however, where
      this is not possible, they have no choice other than to resign themselves to
      leaving home. Furthermore, patients with dementia feel that the medication that
      will allow them to continue their lifestyle at home for long periods is limited.
      Home care for dementia is said to be more difficult than palliative care at home
      for patients with terminal cancer. This paper reports on one case in which
      medication was not and could not be used because the symptoms were too severe.
      However, home care could be continued by preventing the patient 's wife from
      feeling isolated and being able to cope with the prolonged crisis through the
      environmental improvement. 

PMID- 25595081
TI  - [Thoughts and suggestions of pharmacists who participated in a home medical care
      training workshop in a local area].
AB  - We organized a home medical care training workshop to offer community pharmacists
      an opportunity to advance home medical care by allowing pharmacists in regional
      medicine to collaborate with local pharmacist groups. A questionnaire was
      administered to all participants after the workshop. On average, participants
      rated the overall quality of the workshop as 8.46 out of 10. Our results revealed
      that 72.5% of participating pharmacists were experienced in home medical care,
      with the majority having between 5 and 10 years of experience. Participants
      suggested that the qualities necessary for effective home medical care were
      knowledge of home-based care, positive attitude, and coordination with different
      home medical care staff members. Participants also made suggestions for lectures
      in future workshops (e.g., upskilling to improve home medical care expertise). In
      conclusion, participants in a home medical care training workshop primarily
      desired to learn skills for home medical care. To this end, consecutively holding
      the workshop and a cooperation support system with other medical and care
      professionals would be indispensable.

PMID- 25595083
TI  - [The influence of counseling for patients with cancer on their discharge from the
      palliative care support department of the community health care service of Minoh
      City Hospital].
AB  - Counseling for patients with cancer by a certified nurse in palliative care began
      in April 2011 in Minoh City Hospital. Counseling was provided immediately after a
      patient was informed by the treating physician of a primary diagnosis of cancer,
      a metastatic recurrence, or a decision to terminate cancer therapy. We examined
      the patient's support system after the counseling ended. The number of patients
      receiving end-of-life support with home or hospital care rapidly increased from
      118 prior to the program's beginning to 186. The number of patients counseled was
      comparable to the rapid increase in their number(n=68). New cases in the
      outpatient department comprised 59% of all patients, of which, 45% began
      supportive counseling, with 43%of them ultimately returning home. Of the new
      cases receiving counseling in the hospital, 34%eventually returned home after
      discharge, and the highest percentage of discharges were to a palliative care
      unit or hospice program (48%). The initiation of counseling in the outpatient
      department allowed us to provide sufficient time to make decisions about
      appropriate places for end-of-life care. Cooperation with the patients'
      physicians was necessary to provide counseling from the outpatient department.
      Our findings suggest the importance of sharing the patients' medical and social
      information among the staff when necessary.

PMID- 25595082
TI  - [Time analysis of pharmacists' home visit duties].
AB  - Pharmacists' home visit duties include accepting prescriptions, making inquiries
      with the attending physician, preparing medication, giving guidance on
      medication, going on home visits(round trips), and handling insurance claims. In
      the present study, we measured the time required for each duty and determined
      work duration per visit. The study took place during September 2013; the sample
      included 116 subjects and 211 home visits were conducted. Pharmacists' mean work
      duration per visit was 73 min and 15 s; they spent an average of 36 min and 13 s
      of this period on round trips involving home visits and providing guidance on
      medication. Pharmacists are responsible for preparing medication for outpatients;
      therefore, it can be assumed that they can visit patients at their homes only
      during the estimated 2-h period after lunch and before the commencement of
      outpatient service in the evening. Therefore, it is difficult for one pharmacist
      to visit more than five patients a day. The number of patients that each
      pharmacist can visit in one week(6 working days)is estimated at 25-30. 

PMID- 25595084
TI  - [Background of patients receiving peripheral parenteral nutrition after discharge
      from Minoh City Hospital].
AB  - After much debate about the nutritional management of patients at the time of
      discharge, the number of discharged patients receiving peripheral parenteral
      nutrition has increased. We investigated the nutritional management on discharge
      and the background of 2,636 patients discharged from Minoh City Hospital over 7
      years from 2006. Of these, 55 patients (2%)received peripheral parenteral
      nutrition after discharge. In the years preceding 2010, <=7 patients per year
      received peripheral parenteral nutrition after discharge, but this number
      increased to >10 after 2010. More than 60% of the patients were aged >=80 years;
      more than 80% were discharged to a hospital. These patients had terminal-stage
      cancer or high-grade dysphagia, and they required end-of-life medical care. The
      patients' condition, knowledge of their care, and their view of life and death as
      well as the medical treatment environment influenced the choice of nutritional
      support. Correct information is necessary to take appropriate decisions regarding
      nutritional support.

PMID- 25595085
TI  - [Palliative care for patients with hematological malignancies in the Japan
      Baptist Medical Foundation].
AB  - The Japan Baptist Medical Foundation has established a "hospice triangle" system
      consisting of the hospice ward, general ward, and home hospice. Palliative care
      is provided for patients with various types of cancer, including hematological
      malignancies, in the place where they desire to receive care. From December 2010
      to December 2013, 37 patients with hematological malignancies received palliative
      care and died at our foundation. Eleven (30%) patients died in the hospice ward,
      24 (65%) in the general ward, and 2 (5%) at home. The median interval between the
      final dose of chemotherapy and death was 12 (1- 88) days. Twenty (54%) patients
      received transfusions during the last 2 weeks prior to death. Quick response to
      patient situations and early introduction of palliative care are essential to
      support end-of-life decision-making processes, because the clinical course of
      hematological malignancies generally differs from that of other cancers.

PMID- 25595086
TI  - [The current status of home palliative care for patients with advanced cancer at
      the Jikei University School of Medicine].
AB  - Medical oncologists are involved in cancer chemotherapy as well as end-of-life
      care. Recently, an increased number of patients with advanced cancer have
      expressed their preference to receive palliative care at their home during the
      end-of-life period, and several home medical care providers have aimed to provide
      such a service. The number of cancer patients who wish to receive home palliative
      care has also increased at our institution. We reviewed the characteristics of
      advanced cancer patients who received chemotherapy and who eventually received
      homecare from 2012 to 2014. The total number of patients was 22. Of these, 9 had
      breast cancer(40.9%)and 8 had colorectal cancer(36.4%). The median age was
      68(range 36-90) years. Half of these patients died at home. The median duration
      of homecare to death was 64.5(range 12-252)days. Approximately 70% of patients
      were able to remain at home for over a month, but 3 patients died within 2 weeks
      at home and 1 patient returned to the hospital after 10 days of homecare due to
      disease progression. While palliative care in the home setting is valued by many
      cancer patients in the end-of-life period, close monitoring is needed for
      patients with rapidly progressing disease.

PMID- 25595087
TI  - [Assessment of our home care and home palliative care].
AB  - We conducted home care and home palliative care from the department of home care.
      We provided home care services to 190 patients(105 men, 85 women)in October 2013.
      Their average age was 78.7(range: 32-102)years old, and home care had been
      underway from 1 day to 8 years, 10 months. Among all participants,
      168(88.4%)suffered from malignant diseases, 168 patients had died, and over half
      of deceased patients(88 out of 168)had died at home. We used opioids for control
      of cancer pain, carried out home parenteral nutrition(HPN), home enteral
      nutrition(HEN), percutaneous endoscopic gastrostomy( PEG), and removed pleural
      effusion and ascites during home care. In order to facilitate the practice of
      palliative care by the palliative care team, which consists of various medical
      staff in the hospital, we are giving high priority to education and enlightenment
      in the hospital. To provide enlightenment, education, and cooperation between
      regional home care and home palliative care, we are also conducting educational
      lectures in the regional party of the Iwaki city medical associate, and providing
      combined educational-medical training for home care and home palliative care by
      various medical staff.

PMID- 25595088
TI  - [Useful wound management at home].
AB  - In wound care, close observation of the quantity and nature of exudate from a
      wound, and selection of appropriate dressing and/or medication are crucial. Care
      should be taken to prevent wounds with excessive exudate from becoming too moist.
      Furthermore, wound care at home must be easy, which is achievable through the use
      of readily available materials and medications. 1 ) A wound with little to
      moderate exudate should be treated using wrap therapy with perforated
      polyethylene sheets. This therapy can be used to treat pressure ulcers, wounds,
      wounds with slough, and burns. 2 ) An 18-gauge needle can be used to perforate
      wounds with little exudate, such as mild pressure ulcers or wounds with slough,
      and polyurethane film can then be applied. 3 ) Polyurethane film should be
      applied to blisters, pressure ulcers, or similar skin injuries with little
      exudate. 4 ) A hydrocolloid dressing should be used on wounds with light exudate.
      5 ) An ointment containing steroids should be applied to critically colonized
      wounds. 6 ) Melolin dressings, Moiskin Pads, or a disposable diaper should be
      used to manage wounds with heavy exudate.

PMID- 25595089
TI  - [Skin care during non-invasive positive pressure ventilation in nursing home
      residents].
AB  - The purpose of this study was to clarify whether melamine form has efficacy in
      preventing skin care during non-invasive positive pressure ventilation in nursing
      home residents. The study sample comprised 12 people who received non-invasive
      positive pressure ventilation at a nursing home in Osaka, Japan. Results showed
      that residents using melamine form had no significant differences in facial
      shape, though sebum volume, keratinous moisture, impressions, and skin problems
      were all significantly altered.

PMID- 25595090
TI  - [New image of home nursing created by point of care testing (POCT) - examination
      of issues in the introduction of POCT].
AB  - With the rising number of patients who rely on medical care, it is necessary to
      use evolving health care technology appropriately, to control health care costs,
      and to enhance the well-being of patients in the home care setting. Point of care
      testing (POCT)is instrumental system for such demands for home care; however,
      this term remains relatively unknown in Japan. For this research, I conducted a
      qualitative analysis of factors based on stories obtained through group
      interviews of 11 experienced home visiting nurses who work at three home-visit
      nursing stations for the purpose of clarifying issues in the introduction of
      POCT. The results of the research identified five categories and 16 subcategories
      for issues in the introduction of POCT. The identified categories are expected to
      be useful for the spread of POCT in the future. Key words: Point of care testing,
      Home care nursing. 

PMID- 25595091
TI  - [A patient with Creutzfeldt-Jakob disease supported by home medical care from the
      stage of disease progression to death through hospital-clinic cooperation and
      medical-welfare cooperation].
AB  - The patient was a 63-year-old woman who presented with slowness of speech after
      cerebral infarction. Diffusion-weighted MR images and investigations of
      cerebrospinal fluid showed abnormal values, and the patient was diagnosed as
      having sporadic Creutzfeldt-Jakob disease(CJD). This is an intractable disease
      and affects one in one million people; it progresses relatively rapidly,
      eventually resulting in death. For procedures such as intravenous fluid
      replacement and the treatment of pressure sores, we require thorough hand
      washing, eye protection, and disposal of gloves and dressings by incineration. It
      is desirable for patients to spend the limited amount of time available to them
      peacefully at home with their family. Visiting physicians and nurses need to take
      the initiative in sharing information obtained from the CJD infection control
      guidelines and core hospitals with welfare personnel such as caregivers, in order
      to provide correct information on all aspects of patient care and the management
      of this disease in the home environment. Excellent supportive care was provided
      for the patient at home, and she passed away with her family by her side. 

PMID- 25595092
TI  - [Nutritional support to establish refeeding in a patient with acute
      gastrointestinal graft-versus-host disease - a case report].
AB  - A patient with acute myeloid leukemia having acute gastrointestinal graft-versus
      host disease(aGVHD)was provided nutritional support. Oral intake was not
      permitted owing to the gastrointestinal injury induced by aGVHD. Our goal was to
      achieve oral feeding by the time of discharge. The initial aim in reinitiating
      eating was to stimulate intestinal adaptation to the mucosal injury. Via total
      parenteral nutrition(TPN), the patient was provided food in the form of a
      semisolid jelly, which passed through the intestinal tract slowly. After
      interviewing the patient and ascertaining that no complications had arisen owing
      to eating, a regular diet was initiated. Considering the unstable nature of the
      gastrointestinal condition and the associated long-term hospitalization, it is
      important to ensure that the meal contents comply with the patient's taste, while
      considering the patients'uneasiness and fear of progress to oral intake. It is
      difficult to predict improvement of aGVHD. Therefore, it is essential that
      patients are offered meals via TPN, suitable to their intestinal condition and
      mental status. 

PMID- 25595093
TI  - [Prognosis after percutaneous endoscopic gastrostomy (PEG) in patients at home].
AB  - Percutaneous endoscopic gastrostomy(PEG)is a frequently performed operation.
      However, prognosis after PEG is sometimes poor. We investigated the survival rate
      after PEG and prognostic factors in patients at home. The subjects were 75
      patients treated at home who had undergone PEG between January 2006 and December
      2013. Forty-one of the 75 subjects were male and 45 were over 80 years old. The
      surgery was performed because of cerebral infarction in 37 patients, hemorrhagic
      stroke in 13, brain and cervical injuries in 4, encephalitis in 2, and other
      conditions in 19. The survival rate after PEG was 69.4% at 1 year, 34.3% at 3
      years, and 10.3% at 5 years. These scores were lower than the reported survival
      rate of hospital patients. Poor prognostic factors were age >=80, male sex, a
      serum albumin level<=2.5mg/dL, repeat occurrences of pneumonia, and disturbance
      of consciousness. 

PMID- 25595094
TI  - [New home enteral nutrition via jejunostomy using semi-solid enteral formula].
AB  - Home enteral nutrition via jejunostomy requires considerable time for infusion to
      the patients. A new method using semisolid enteral formula dramatically reduces
      the time of infusion. This method makes use of pectin and liquid enteral formula.
      The authors applied this method in two patients with total gastrectomy being
      given enteral nutrition at home. There were no complications such as diarrhea or
      abdominal pain. This new method of home enteral nutrition could enhance the
      patients' quality of life (QOL) by reducing the time of infusion of enteral
      nutrition.

PMID- 25595095
TI  - High production of small organic dicarboxylate dianions by DESI and ESI.
AB  - A significant production of gas-phase dicarboxylate dianions has been observed in
      standard ESI and DESI during the analysis of small organic dicarboxylic acids
      under moderate or highly alkaline conditions. In ESI, this can be attributed to
      an excess of hydroxyl ions (OH(-)) which favor the formation of an high amount of
      dianions in solution, contemporarily trapping the potential counter ions during
      the ESI process. The results obtained in DESI highlight the role of the surface
      in trapping the counter-ions during desorption process and determining the
      ultimate nature of the observed gas-phase ions. 

PMID- 25595096
TI  - Negative pressure wound therapy in grade IIIB tibial fractures: fewer infections
      and fewer flap procedures?
AB  - BACKGROUND: Grade IIIB open tibia fractures are devastating injuries. Some
      clinicians advocate wound closure or stable muscle flap coverage within 72 hours
      to limit complications such as infection. Negative pressure wound therapy was
      approved by the FDA in 1997 and has become an adjunct for many surgeons in
      treating these fractures. Opinions vary regarding the extent to which negative
      pressure wound therapy contributes to limb salvage. Evidence-based practice
      guidelines are limited for use of negative pressure wound therapy in Grade IIIB
      tibia fractures. This systematic literature review of negative pressure wound
      therapy in Grade IIIB tibia fractures may substantiate current use and guide
      future studies. QUESTIONS/PURPOSES: We sought to answer the following: (1) Does
      the use of negative pressure would therapy compared with gauze dressings lead to
      fewer infections? (2) Does it allow flap procedures to be performed safely beyond
      72 hours without increased infection rates? (3) Is it associated with fewer local
      or free flap procedures? METHODS: We conducted a systematic review of six large
      databases (through September 1, 2013) for studies reporting use of negative
      pressure wound therapy in Grade IIIB open tibia fractures, including information
      regarding infection rates and soft tissue reconstruction. The systematic review
      identified one randomized controlled trial and 12 retrospective studies: four
      studies compared infection rates between negative pressure wound therapy and
      gauze dressings, 10 addressed infection rates with extended use, and six reported
      on flap coverage rates in relation to negative pressure wound therapy use beyond
      72 hours. None of the 13 studies was eliminated owing to lack of study quality.
      RESULTS: Negative pressure wound therapy showed a decrease in infection rates
      over rates for gauze dressings in two of four studies (5.4% [two of 35] versus
      28% [seven of 25], and 8.4% [14 of 166] versus 20.6% [13 of 63]), an equivalent
      infection rate in one study (15% [eight of 53] versus 14% [five of 16]), and an
      increased infection rate in the fourth study (29.5% [23 of 78] versus 8% [two of
      25]). In terms of the second question regarding infection rates with negative
      pressure wound therapy beyond 72 hours, eight of 10 studies concluded there was
      no increase in infection rates, whereas two of 10 reported an increase in
      infection rates associated with negative pressure wound therapy use beyond 72
      hours. Infection rates varied from 0% to 57% in these 10 studies. Five studies
      reported low infection rates of 0% to 7% and five reported rates of 27% to 57%.
      The third question (addressed by six studies) regarded the potential decreased
      use of a soft tissue flap in patients treated with extended negative pressure
      wound therapy. Flap rates were reduced by 13% to 60% respectively compared with
      those of historical controls. Grade IIIB tibia fractures by definition required
      soft tissue procedures. The patients in these six studies had Grade IIIB tibia
      fractures after the first debridement. However, after extended negative pressure
      wound therapy, fewer patients required flaps than grading at the first
      debridement would have predicted. CONCLUSIONS: There is an increasing body of
      data supporting negative pressure wound therapy as an adjunctive modality at all
      stages of treatment for Grade IIIB tibia fractures. There is an association
      between decreased infection rates with negative pressure wound therapy compared
      with gauze dressings. There is evidence to support negative pressure wound
      therapy beyond 72 hours without increased infection rates and to support a
      reduction in flap rates with negative pressure wound therapy. However, negative
      pressure wound therapy use for Grade IIIB tibia fractures requires extensive
      additional study. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 25595098
TI  - Reply to letter to the editor.

PMID- 25595097
TI  - Postprandial triglyceride-rich lipoproteins regulate perilipin-2 and perilipin-3
      lipid-droplet-associated proteins in macrophages.
AB  - Lipid accumulation in macrophages contributes to atherosclerosis. Within
      macrophages, lipids are stored in lipid droplets (LDs); perilipin-2 and perilipin
      3 are the main LD-associated proteins. Postprandial triglyceride (TG)-rich
      lipoproteins induce LD accumulation in macrophages. The role of postprandial
      lipoproteins in perilipin-2 and perilipin-3 regulation was studied. TG-rich
      lipoproteins (TRLs) induced the levels of intracellular TGs, LDs and perilipin-2
      protein expression in THP-1 macrophages and in Apoe(-/-) mice bone-marrow-derived
      macrophages with low and high basal levels of TGs. Perilipin-3 was only
      synthesized in mice macrophages with low basal levels of TGs. The regulation was
      dependent on the fatty acid composition of the lipoproteins; monounsaturated and
      polyunsaturated fatty acids (PUFAs) more strongly attenuated these effects
      compared with saturated fatty acids. In THP-1 macrophages, immunofluorescence
      microscopy and freeze-fracture immunogold labeling indicated that the
      lipoproteins translocated perilipin-3 from the cytoplasm to the LD surface; only
      the lipoproteins that were rich in PUFAs suppressed this effect. Chemical
      inhibition showed that lipoproteins induced perilipin-2 protein expression
      through the peroxisome proliferator-activated nuclear receptor (PPAR) PPARalpha
      and PPARgamma pathways. Overall, our data indicate that postprandial TRLs may be
      involved in atherosclerotic plaque formation through the regulation of perilipin
      2 and perilipin-3 proteins in macrophages. Because the fatty acid composition of
      the lipoproteins is dependent on the type of fat consumed, the ingestion of olive
      oil, which is rich in monounsaturated fatty acids, and fish oil, which is rich in
      omega-3 fatty acids, can be considered a good nutritional strategy to reduce the
      risk of atherosclerosis by LD-associated proteins decrease. 

PMID- 25595099
TI  - Robot-assisted radical cystectomy and urinary diversion: technical
      recommendations from the Pasadena Consensus Panel.
AB  - BACKGROUND: The technique of robot-assisted radical cystectomy (RARC) has evolved
      significantly since its inception >10 yr ago. Several high-volume centers have
      reported standardized techniques with refinements and subsequent outcomes.
      OBJECTIVE: To review all existing literature on RARC and urinary diversion
      techniques and summarize key points that may affect oncologic, surgical, and
      functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Pasadena Consensus
      Panel on RARC and urinary reconstruction convened May 3-4, 2014, to review the
      existing peer-reviewed literature and create recommendations for best practice.
      The panel consisted of experts in open radical cystectomy and RARC. No commercial
      support was received. SURGICAL PROCEDURE: The consensus panel extensively
      reviewed the surgical technique of RARC in men and women, extended pelvic lymph
      node dissection, extracorporeal urinary diversion, and intracorporeal urinary
      diversion. Critical aspects of the technique are described. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Preoperative, operative, and postoperative parameters
      from the largest and most contemporary RARC series, stratified by urinary
      diversion technique, are presented. RESULTS AND LIMITATIONS: Preoperative,
      operative, and postoperative measures of RARC technique adhere closely to the
      standards established in open surgery. CONCLUSIONS: Refinement of techniques for
      RARC and urinary diversion over the past 10 yr has made it safe, reproducible,
      and oncologically sound. PATIENT SUMMARY: We summarize the critical aspects of
      surgical techniques reviewed at the Pasadena international consensus meeting on
      RARC and urinary reconstruction. Preoperative, operative, and postoperative
      measures of RARC technique adhere closely to the standards established in open
      surgery.

PMID- 25595101
TI  - Cannabinoid agonists rearrange synaptic vesicles at excitatory synapses and
      depress motoneuron activity in vivo.
AB  - Impairment of motor skills is one of the most common acute adverse effects of
      cannabis. Related studies have focused mainly on psychomotor alterations, and
      little is known about the direct impact of cannabinoids (CBs) on motoneuron
      physiology. As key modulators of synaptic function, CBs regulate multiple
      neuronal functions and behaviors. Presynaptic CB1 mediates synaptic strength
      depression by inhibiting neurotransmitter release, via a poorly understood
      mechanism. The present study examined the effect of CB agonists on excitatory
      synaptic inputs incoming to hypoglossal motoneurons (HMNs) in vitro and in vivo.
      The endocannabinoid anandamide (AEA) and the synthetic CB agonist WIN 55,212-2
      rapidly and reversibly induced short-term depression (STD) of glutamatergic
      synapses on motoneurons by a presynaptic mechanism. Presynaptic effects were
      fully reversed by the CB1-selective antagonist AM281. Electrophysiological and
      electron microscopy analysis showed that WIN 55,212-2 reduced the number of
      synaptic vesicles (SVs) docked to active zones in excitatory boutons. Given that
      AM281 fully abolished depolarization-induced depression of excitation,
      motoneurons can be feasible sources of CBs, which in turn act as retrograde
      messengers regulating synaptic function. Finally, microiontophoretic application
      of the CB agonist O-2545 reversibly depressed, presumably via CB1, glutamatergic
      inspiratory-related activity of HMNs in vivo. Therefore, evidence support that
      CBs, via presynaptic CB1, induce excitatory STD by reducing the readily
      releasable pool of SVs at excitatory synapses, then attenuating motoneuron
      activity. These outcomes contribute a possible mechanistic basis for cannabis
      associated motor performance disturbances such as ataxia, dysarthria and
      dyscoordination.

PMID- 25595100
TI  - Anthocyanins and phenolic acids from a wild blueberry (Vaccinium angustifolium)
      powder counteract lipid accumulation in THP-1-derived macrophages.
AB  - PURPOSE: Blueberries are a rich source of anthocyanins (ACNs) and phenolic acids
      (PA), which are hypothesized to protect against development of atherosclerosis.
      The present study examined the effect of an ACN- and PA-rich fractions, obtained
      from a wild blueberry powder, on the capacity to counteract lipid accumulation in
      macrophages derived from monocytic THP-1 cells. In addition, we tested the
      capacity of pure ACNs and their metabolites to alter lipid accumulation. METHODS:
      THP-1-derived macrophages were incubated with fatty acids (500 MUM oleic/palmitic
      acid, 2:1 ratio) and different concentrations (from 0.05 to 10 MUg mL(-1)) of ACN
      and PA-rich fractions, pure ACN standards (malvidin, delphinidin and cyanidin 3
      glucoside), and metabolites (syringic, gallic and protocatechuic acids). Lipid
      accumulation was quantified with the fluorescent dye Nile red. RESULTS: Lipid
      accumulation was reduced at all concentrations of the ACN-rich fraction tested
      with a maximum reduction at 10 MUg mL(-1) (-27.4%; p < 0.0001). The PA-rich
      fraction significantly reduced the lipid accumulation only at the low
      concentrations from 0.05 ug mL(-1) to 0.3 ug mL(-1), with respect to the control
      with fatty acids. Supplementation with pure ACN compounds (malvidin and
      delphinidin-3-glucoside and its metabolic products (syringic and gallic acid))
      reduced lipid accumulation especially at the low concentrations, while no
      significant effect was observed after cyanidin-3-glucoside and protocatechuic
      acid supplementation. CONCLUSIONS: The results demonstrated a potential role of
      both the ACN- and PA-rich fractions and single compounds in the lipid
      accumulation also at concentrations close to that achievable in vivo.

PMID- 25595103
TI  - Computational identification and binding analysis of orphan human cytochrome P450
      4X1 enzyme with substrates.
AB  - BACKGROUND: Cytochrome P450s (CYPs) are important heme-containing proteins, well
      known for their monooxygenase reaction. The human cytochrome P450 4X1 (CYP4X1) is
      categorized as "orphan" CYP because of its unknown function. In recent studies it
      is found that this enzyme is expressed in neurovascular functions of the brain.
      Also, various studies have found the expression and activity of orphan human
      cytochrome P450 4X1 in cancer. It is found to be a potential drug target for
      cancer therapy. However, three-dimensional structure, the active site topology
      and substrate specificity of CYP4X1 remain unclear. METHODS: In the present
      study, the three-dimensional structure of orphan human cytochrome P450 4X1 was
      generated by homology modeling using Modeller 9v8. The generated structure was
      accessed for geometrical errors and energy stability using PROCHECK, VERFIY 3D
      and PROSA. A molecular docking analysis was carried out against substrates
      arachidonic acid and anandamide and the docked substrates were predicted for drug
      likeness, ADME-Tox parameters and biological spectrum activity. RESULTS: The
      three-dimensional model of orphan human cytochrome P450 4X1 was generated and
      assessed with various structural validation programmes. Docking of orphan human
      cytochrome P450 4X1 with arachidonic acid revealed that TYR 112, ALA 126, ILE
      222, ILE 223, THR 312, LEU 315, ALA 316, ASP 319, THR 320, PHE 491 and ILE 492
      residues were actively participating in the interaction, while docking of CYP4X1
      with anandamide showed that TYR 112, GLN 114, PRO 118, ALA 126, ILE 222, ILE 223,
      SER 251, LEU 315, ALA 316 and PHE 491 key residues were involved in strong
      interaction. CONCLUSION: From this study, several key residues were identified to
      be responsible for the binding of arachidonic acid and anandamide with orphan
      human cytochrome P450 4X1. Both substrates obeyed Lipinski rule of five in drug
      likeness test and biological spectrum prediction showed anticarcinogenic
      activity. Compared to anandamide, arachidonic acid showed strong interaction with
      cytochrome P450 4X1 and also less health effect in certain human system in ADME
      Tox prediction. These findings provide useful information on the biological role
      and structure-based drug design of orphan human cytochrome P450 4X1.

PMID- 25595102
TI  - Engineered alpha4beta2 nicotinic acetylcholine receptors as models for measuring
      agonist binding and effect at the orthosteric low-affinity alpha4-alpha4
      interface.
AB  - The nicotinic acetylcholine receptor alpha4beta2 is important for normal
      mammalian brain function and is known to express in two different
      stoichiometries, (alpha4)2(beta2)3 and (alpha4)3(beta2)2. While these are similar
      in many aspects, the (alpha4)3(beta2)2 stoichiometry differs by harboring a third
      orthosteric acetylcholine binding site located at the alpha4-alpha4 interface.
      Interestingly, the third binding site has, so far, only been documented using
      electrophysiological assays, actual binding affinities of nicotinic receptor
      ligands to this site are not known. The present study was therefore aimed at
      determining binding affinities of nicotinic ligands to the alpha4-alpha4
      interface. Given that epibatidine shows large functional potency differences at
      alpha4-beta2 vs. alpha4-alpha4 interfaces, biphasic binding properties would be
      expected at (alpha4)3(beta2)2 receptors. However, standard saturation binding
      experiments with [(3)H]epibatidine did not reveal biphasic binding under the
      conditions utilized. Therefore, an engineered beta2 construct (beta2(HQT)), which
      converts the beta(-) face to resemble that of an alpha4(-) face, was utilized to
      create (alpha4)3(beta2(HQT))2 receptors harboring three alpha4-alpha4 interfaces.
      With this receptor, low affinity binding of epibatidine with a Kd of ~5 nM was
      observed in sharp contrast to a Kd value of ~10 pM observed for wild-type
      receptors. A strong correlation between binding affinities at the
      (alpha4)3(beta2(HQT))2 receptor and functional potencies at the wild-type
      receptor of a range of nicotinic ligands highlighted the validity of using the
      mutational approach. Finally, large differences in activities at alpha4-beta2 vs.
      alpha4-alpha4 interfaces were observed for structurally related agonists
      underscoring the need for establishing all binding parameters of compounds at
      alpha4beta2 receptors. 

PMID- 25595104
TI  - Prospective study of a single treatment strategy for local tumescent anesthesia
      in Muller phlebectomy.
AB  - BACKGROUND: Ambulatory Muller phlebectomy for varicose veins can be performed
      under local anesthesia. However, subcutaneous injection of local tumescent
      anesthetics may cause discomfort because of acidity of the solution. Addition of
      sodium bicarbonate lowers the acidity of anesthetic solutions, which might cause
      less pain. The objective of this study was to study whether alkalinization of the
      local anesthetic solution with sodium bicarbonate 1.4% decreases perioperative
      pain during Muller phlebectomies. METHODS: It is a double-blind single-center
      randomized controlled trial. In all, 101 patients scheduled for ambulatory Muller
      phlebectomy were randomized to receive either local anesthesia with alkalinized
      solution (lidocaine 1% and epinephrine in sodium bicarbonate 1.4%) or standard
      solution (lidocaine 1% and epinephrine in saline 0.9%). Primary outcome was pain
      during injection of local anesthetics with the use of the Visual Analogue Scale
      (VAS). Secondary outcomes were peroperative and postoperative pain, use of
      analgesics, patient satisfaction, return to function, and complications. RESULTS:
      Patients receiving subcutaneous injection of local anesthetics diluted in sodium
      bicarbonate 1.4% experienced significantly less pain during injection compared
      with patients treated with standard anesthetic solution (VAS, 1.75 +/- 1.8 vs.
      3.55 +/- 2.2, P < 0.00). Peroperative and postoperative pain, complication rates,
      use of analgesics, patient satisfaction, return to function, and complications
      did not differ between the 2 groups (P > 0.10). CONCLUSIONS: Alkalinization of
      local anesthetic solution with sodium bicarbonate 1.4% significantly improves
      patient comfort during injection of local tumescent anesthesia.

PMID- 25595105
TI  - Atheromatous occlusive lesions of the popliteal artery treated with stent grafts:
      predictive factors of midterm patency.
AB  - BACKGROUND: Because of its location, the popliteal artery is exposed to important
      biomechanical constraints, inducing a specific risk of thrombosis of stents,
      little studied in the literature. The objective of this monocentric retrospective
      study was to evaluate the patency of stents implanted in the popliteal artery to
      treat atheromatous lesions and the risk factors predisposing to thrombosis.
      METHODS: Between January 2009 and July 2013, all the patients receiving stents
      for a residual stenosis or a complication of angioplasty in the popliteal artery
      or the distal anastomosis of a femoropopliteal bypass were included
      retrospectively and in an intention to treat. Forty-six patients (17 women), with
      a 71.5 years median age (range, 45-90 years), including 17 diabetic patients
      (37%) and 7 hemodialysis patients (15%), were operated in 51 limbs for
      claudication (n = 25, 49%), critical ischemia (n = 18, 35%), or acute ischemia (n
      = 8, 16%). Thirty stenoses >70% (59%) and 21 thromboses (41%) were treated with
      56 autoexpandable stents, with an average diameter of 6 mm (range, 5-8 mm) and an
      average length of 5 cm (range, 4-15 cm), including 39 lesions in P1 (above the
      patella), 8 in P2 (articular), and 4 in P3 (distal popliteal artery). The
      following factors were analyzed according to univariate and multivariate models:
      age, gender, Society for Vascular Surgery score, symptomatology, type and
      location of lesion, number of stents deployed, and dimension of stents. RESULTS:
      Technical success was of 98% (n = 50), including 1 insufficient result of the
      endovascular treatment. At 30 days, one patient treated for critical ischemia
      died (2%) and one residual popliteal stenosis was treated by bypass (2%). After a
      27.6 +/- 10.07 month follow-up, restenosis (>50%) was detected in 5 cases
      including 4 asymptomatic and a popliteal thrombosis occurred in 9 cases,
      including 3 asymptomatic cases. Eight secondary interventions were necessary,
      including 4 endovascular procedures, 3 bypasses, and only 1 major amputation
      (thigh). The primary and secondary patencies at 12 months and 24 months were 80%
      and 65%, and 90% and 74%, respectively. The multivariate analysis showed that the
      type of lesion (stenosis versus occlusion; odds ratio [OR], 5.1; 95% confidence
      interval [CI], 1.2-22.9, P = 0.032) and the number of stents implanted (1 vs. 2
      stents; OR [95% CI], 12.7 [1.8-88.5]; P = 0.011) were independent predictive
      factors of secondary thrombosis. CONCLUSIONS: The endovascular treatment of the
      atheromatous popliteal lesions appears to be a satisfactory alternative. The
      implantation of 1 stent in the popliteal artery is recommended in the event of
      popliteal occlusion, whereas for a stenosis, it must be reserved for patients
      with residual stenosis or in the event of complications of angioplasty, such as
      dissection or elastic recoil. Stent must be single, with deployment of a long
      stent in the event of long lesion.

PMID- 25595107
TI  - Clinical features and endovascular treatment of visceral artery pseudoaneurysms.
AB  - BACKGROUND: To analyze our experience with clinical features and endovascular
      treatment of visceral artery pseudoaneurysms (VAPAs). METHODS: We performed
      endovascular treatments on 52 patients (34 men and 18 women) affected by VAPA.
      These cases were pseudoaneurysms of the celiac axis, superior mesenteric artery,
      and their branches. Endovascular treatments of VAPA using isolation techniques
      were performed after failure of conservative treatments. Follow-up was carried
      out via assessment of contrast-enhanced computed tomography or computed
      tomography angiography images. RESULTS: The initial technical success rate of
      endovascular treatment is 100% with only 4 patients rebled during 2-week follow
      up. One patient among no rebleeding died of multisystem organ failure 28 days
      after intervention; thus, 30-day mortality rate was 1.9%. Four patients (7.7%)
      required secondary interventions because of rebleeding and were successfully
      treated by reintervention; however, one of the patients died from uncontrolled
      sepsis 39 days after reintervention. Postembolization syndrome developed in 3
      patients (5.8%); one of these patients underwent splenectomy. During follow-up,
      no change of hepatic function was observed, no bowel ischemia was reported, and
      VAPA remained absent in all patients. CONCLUSIONS: Endovascular management is
      minimally invasive and highly successful in treating VAPA. It is particularly
      useful in poor surgical candidates.

PMID- 25595106
TI  - Tolerance of rapid right ventricular pacing during thoracic endovascular aortic
      repair.
AB  - BACKGROUND: The objective of this retrospective study was to evaluate the
      tolerance of rapid right ventricular pacing (RRVP) compared with that of the
      traditional methods of hypotension used during thoracic endovascular aortic
      repair (TEVAR). METHODS: From January 2002 to December 2012, we retrospectively
      included all the patients treated with TEVAR by comparing the 2 groups: patients
      operated with RRVP (RRVP+) and those operated without RRVP (RRVP-). The
      characteristics of the population and the procedures were recorded. The rates of
      complications were compared up to 1 year. RESULTS: Sixty-one patients were
      operated. Treated pathologies were multiple with 19 aneurysms, 14 false
      aneurysms, 12 isthmic ruptures, 11 dissections, 3 coarctations, and 2 endoleaks.
      Twenty-four patients were RRVP+ and 37 patients were RRVP-. Mortality rates at 1
      month in groups RRVP+ and RRVP- were of 0% and 2.7%, respectively (P = 1), and
      reintervention rates were 0% and 13.5%, respectively (P = 0.15). Three
      peroperative rhythm disorders (12.5%) were observed in the RRVP+ group including
      2 ventricular fibrillations and 1 atrial fibrillation, both reduced without
      complications. One pacemaker was implanted for atrioventricular block in the RRVP
      group. In the RRVP+ group, 83.3% of the patients presented a rise in troponin Ic
      (TnI) >0.04 ng/mL in 72 hours compared with 40.5% of the patients in the RRVP-
      group (P = 0.0013), with a spontaneously favorable evolution. No coronary
      syndrome was observed at 1 year with a mortality rate of 10.8% in the RRVP- group
      vs. 0% in the RRVP+ (P = 0.15). CONCLUSIONS: In spite of a frequent moderate rise
      of TnI at the time of RRVP, this technique does not present more complications at
      1 year than the use of a chemical hypotension. It thus seems an interesting
      alternative for selected patients, in trained teams.

PMID- 25595108
TI  - Early and midterm results of kissing stent technique in the management of
      aortoiliac obstructive disease.
AB  - BACKGROUND: To retrospectively analyze the early and the midterm results of
      endovascular management of aortoiliac obstructive disease with the kissing stent
      technique. METHODS: From January 2005 to September 2012, 229 consecutive
      endovascular interventions for aortoiliac obstructive disease were performed;
      data from all the interventions were prospectively collected in a dedicated
      database. In 41 patients, the kissing stent technique at the level of aortic
      bifurcation was performed (group 1), whereas in the remaining 188 it was not
      (group 2). Perioperative results were compared with chi-squared test. Follow-up
      results were analyzed with Kaplan-Meier curves and compared with log-rank test.
      RESULTS: Trans-Atlantic Inter-Society Consensus II C and D lesions were present
      in 66% of patients in group 1 and in 28.5% in group 2 (P < 0.001), whereas iliac
      occlusion rather than stenosis was detected in 78% of patients in group 1 and in
      50% in group 2 (P = 0.001). The mean number of placed stents was 2.5 in group 1
      and 1.4 in group 2 (P < 0.001). Technical success was 100% in group 1 and 98% in
      group 2 (P = 0.3). The rate of perioperative complications was 7.3% in group 1
      and 4.2% in group 2 (P = 0.4). At 30 days, neither deaths nor major
      cardiovascular complications occurred. There was no thrombosis or significant
      restenosis at the early postoperative follow-up visit. Mean duration of follow-up
      was 22 months. Primary patency rates at 4 years were 70.5% (standard error [SE],
      0.09) in group 1 and 75.5% (SE, 0.06) in group 2 (P = 0.7). At the same interval,
      assisted primary and secondary patency and survival rates were also similar;
      reintervention rates were 15.5% in group 1 (SE, 0.1) and 19.5% in group 2 (SE,
      0.06; P = 0.6). CONCLUSIONS: The kissing stent technique provided satisfactory
      results in patients with obstructive aortoiliac diseases, without an increase in
      immediate and midterm complications, representing an effective solution in
      complex anatomies.

PMID- 25595110
TI  - Trend, Risk Factors, and Costs of Clostridium difficile Infections in Vascular
      Surgery.
AB  - BACKGROUND: Starting in December 2013, the Hospital Inpatient Quality Reporting
      Program included Clostridium difficile infection (CDI) rates as a new publically
      reported quality measure. Our goal was to review the trend, hospital variability
      in CDI rates, and associated risk factors and costs in vascular surgery. METHODS:
      The rates of CDI after major vascular procedures including aortic abdominal
      aneurysm (AAA) repair, carotid endarterectomy or stenting, lower extremity
      revascularization (LER), and LE amputation were identified using Nationwide
      Inpatient Sample database for 2000-2011. Risk factors associated with CDI were
      analyzed with hierarchical multivariate logistic regression. Extra costs, length
      of stay (LOS), and mortality were assessed for propensity-matched
      hospitalizations with and without CDI. RESULTS: During the study period, the
      rates of CDI after vascular procedures had increased by 74% from 0.6 in 2000 to
      1.05% in 2011, whereas the case fatality rate was stable at 9-11%. In 2011, the
      highest rates were after ruptured aortic abdominal aneurysm (rAAA) repair (3.3%),
      followed by lower extremity amputations (2.3%) and elective open AAA (1.3%). The
      rates of CDI increased after all vascular procedures during the 12 years. The
      highest increase was after endovascular LER (151.8%) and open rAAA repair
      (135.7%). In 2011, patients who had experienced CDI had median LOS of 15 days
      (interquartile range, 9-25 days) compared with 8.3 days for matched patients
      without CDI, in-hospital mortality 9.1% (compared with 5.0%), and $13,471 extra
      cost per hospitalization. The estimated cost associated with CDI in vascular
      surgery in the United States was ~$98 million in 2011. Hospital rates of CDI
      varied from 0 to 50% with 3.5% of hospitals having infection rates >=5%. Factors
      associated with CDI included multiple chronic conditions, female gender, surgery
      type, emergent and weekend hospitalizations, hospital transfers, and urban
      locations. CONCLUSIONS: Despite potential reduction of infection rates as
      evidenced by the experience of hospitals with effective interventions, CDI is
      increasing among vascular surgery patients. It is associated with prolonged LOS,
      increased mortality, and higher costs.

PMID- 25595109
TI  - Spontaneous and isolated dissection of the superior mesenteric artery: proposal
      of a management algorithm.
AB  - BACKGROUND: Spontaneous and isolated dissection of the superior mesenteric artery
      (SIDSMA) is a rare pathology, and the treatment of symptomatic forms is not
      consensual. The objective of this study was to analyze the management of a series
      of patients presenting a symptomatic SIDSMA within a structure taking care of
      intestinal vascular emergencies. METHODS: From January 2010 to January 2014, the
      patients presenting a symptomatic SIDSMA were included retrospectively. The
      clinical and radiologic data as well as the treatment and the follow-up were
      analyzed. RESULTS: Nine patients were included. Among them, 2 patients presenting
      with acute mesenteric ischemia were revascularized surgically in emergency, and 1
      patient presenting a rupture of a superior mesenteric artery aneurysm had an
      arteriography followed by medical care. The 6 other patients received medical
      treatment. Among these, 2 patients developed mesenteric angina requiring surgical
      revascularization during the follow-up. CONCLUSIONS: The revascularization of
      spontaneous and isolated dissections of the superior mesenteric artery is
      indicated in the cases complicated with acute mesenteric ischemia, aneurysmal
      rupture, or in the event of appearance of mesenteric angina or aneurysmal
      evolution. It should also be discussed in the event of failure of the medical
      treatment.

PMID- 25595112
TI  - Management of spontaneous isolated visceral artery dissection.
AB  - BACKGROUND: Spontaneous isolated dissection of the celiac artery (CA) or the
      superior mesenteric artery (SMA) is rare but increasingly recognized because of
      widespread use of advanced abdominal imaging technology. Indications for specific
      therapeutic options and long-term outcomes are not well defined. This study
      analyzed clinical features, management strategies, and outcomes for patients with
      spontaneous visceral artery dissections. METHODS: Medical records of all patients
      diagnosed with CA or SMA dissections at 2 institutions (Scripps Green Hospital
      and San Diego Kaiser Medical Center) between January 2005 and January 2014 were
      retrospectively reviewed. Patient demographics included age, symptoms, associated
      comorbidities, and type of intervention. Anatomic features including length of
      dissection and entry point were measured. Efficacy of the various treatments was
      compared on the basis of symptom resolution and clinical course. RESULTS: Over an
      8-year period, 23 patients with a diagnosis of visceral artery dissection were
      identified. Eighteen (78%) patients were men. Most patients (78%) were
      symptomatic on initial presentation with abdominal or back pain. Treatment
      included observation in 4, anticoagulation in 13, and endovascular stenting in 6
      patients. The mean follow-up was 23.8 months. No patient required bowel
      resection. Twenty of twenty-three patients reported resolution of symptoms at
      follow-up. CONCLUSIONS: In this series, all patients with isolated visceral
      artery dissection had favorable outcomes, with no significant morbidity or
      mortality. Conservative management with anticoagulation is recommended as the
      first-line therapy. When conservative management fails, endovascular therapy is
      the treatment of choice.

PMID- 25595111
TI  - Intranuclear expression of progesterone receptors in smooth muscle cells of
      renovascular fibromuscular dysplasia: a pilot study.
AB  - BACKGROUND: The pathogenesis of fibromuscular dysplasia (FMD) remains poorly
      understood. Yet, understanding this mechanism has taken on new urgency after
      recent evidence indicating that FMD is not as rare as previously thought. We
      speculated that hormonal receptors in the walls of dysplastic renal arteries were
      implicated in the pathogenesis of FMD. METHODS: We undertook a pilot prospective
      case-control study comparing histologic findings from renal arteries that were
      surgically removed in 2 patient groups. The case group included 6 samples from
      FMD patients who underwent surgery for stenosis or aneurysm caused by FMD. The
      control group included 3 FMD-free patients who underwent nephrectomy for
      nonvascular causes. Surgical specimens were sent to the histology laboratory. FMD
      was defined preoperatively using conventional radiologic criteria and was
      confirmed by histologic examination. RESULTS: Immunohistochemical staining
      detected intense progesterone receptor expression in the nuclei of smooth muscle
      cells in FMD patients. No progesterone receptor expression was found in the FMD
      free patients. Estrogen receptor expression was not noted in the 2 groups.
      CONCLUSIONS: This preliminary finding may suggest that progesterone plays a key
      role in the pathogenesis of FMD and opens the fields of genetic and therapeutic
      approaches.

PMID- 25595113
TI  - Arm veins versus contralateral greater saphenous veins for lower extremity bypass
      reconstruction: preliminary data of a randomized study.
AB  - BACKGROUND: The aim of this randomized study was to determine whether arm vein
      (AV) or contralateral greater saphenous vein (CGSV) is the better alternative
      vein source for lower extremity bypass reconstruction. METHODS: Consecutive
      patients with absent ipsilateral greater saphenous vein undergoing lower
      extremity revascularization were allocated to group A (AV bypass) or B (CGSV
      bypass). RESULTS: From 6, 2010, to 11, 2013, 64 patients (32 each group) were
      randomized. In all, 29 of 93 patients had to be excluded for various reasons.
      Median age was 76 years vs. 71 years (P = 0.01) for group A and B patients. There
      were no statistically significant differences regarding gender, cardiovascular
      risk factors, redo bypass procedures (P = 0.77), below-knee bypass procedures (P
      = 0.61), median bypass length (P = 0.6), and median length of incision on
      ipsilateral leg to perform anastomoses (P = 0.2) between group A and B patients,
      respectively. Incisions for vein harvest were longer in group A (P = 0.003).
      Overall surgical site infections (SSIs, P = 1.0) and SSI from vein harvest (P =
      1.0) were equally distributed. No patient was lost to follow-up (17 vs. 18
      months, P = 0.74). There was no statistically significant difference regarding
      primary (P = 0.77) and secondary (P = 0.25) patency rates at 1 year (group A: 52%
      vs. group B: 54% and group A: 72% vs. group B: 61%) and at 2 years (52% vs. 48%
      and 64% vs. 61%), respectively. There were 4 vs. 6 major amputations (P = 0.23)
      and 5 vs. 2 deaths (P = 0.1) in groups A and B during follow-up. CONCLUSIONS:
      Preliminary results suggest that both AV and CGSV may serve as a secondary vein
      bypass graft equally well.

PMID- 25595115
TI  - Mathematics as verbal behavior.
AB  - "Behavior which is effective only through the mediation of other persons has so
      many distinguishing dynamic and topographical properties that a special treatment
      is justified and indeed demanded" (Skinner, 1957, p. 2). Skinner's demand for a
      special treatment of verbal behavior can be extended within that field to domains
      such as music, poetry, drama, and the topic of this paper: mathematics. For
      centuries, mathematics has been of special concern to philosophers who have
      continually argued to the present day about what some deem its "special nature."
      Two interrelated principal questions have been: (1) Are the subjects of
      mathematical interest pre-existing in some transcendental realm and thus are
      "discovered" as one might discover a new planet; and (2) Why is mathematics so
      effective in the practices of science and engineering even though originally such
      mathematics was "pure" with applications neither contemplated or even desired? I
      argue that considering the actual practice of mathematics in its history and in
      the context of acquired verbal behavior one can address at least some of its
      apparent mysteries. To this end, I discuss some of the structural and functional
      features of mathematics including verbal operants, rule-and contingency-modulated
      behavior, relational frames, the shaping of abstraction, and the development of
      intuition. How is it possible to understand Nature by properly talking about it?
      Essentially, it is because nature taught us how to talk. 

PMID- 25595114
TI  - Incubation of ethanol reinstatement depends on test conditions and how ethanol
      consumption is reduced.
AB  - In reinstatement studies (a common preclinical procedure for studying relapse),
      incubation occurs (longer abstinence periods result in more responding). This
      finding is discordant with the clinical literature. Identifying determinants of
      incubation could aid in interpreting reinstatement and identifying processes
      involved in relapse. Reinstated responding was examined in rats trained to
      respond for ethanol and food under a multiple concurrent schedule (Component 1:
      ethanol FR5, food FR150; Component 2: ethanol FR5, food FR5-alternating across
      the 30-min session). Ethanol consumption was then reduced for 1 or 16 sessions
      either by suspending training (rats remained in home cage) or by providing
      alternative reinforcement (only Component 2 stimuli and contingencies were
      presented throughout the session). In the next session, stimuli associated with
      Component 1 were presented and responses recorded but ethanol and food were never
      delivered. Two test conditions were studied: fixed-ratio completion either
      produced ethanol- or food-associated stimuli (signaled) or had no programmed
      consequence (unsignaled). Incubation of ethanol responding was observed only
      after suspended training during signaled test sessions. Incubation of food
      responding was also observed after suspended training. These results are most
      consistent with incubation resulting from a degradation of feedback functions
      limiting extinction responding, rather than from increased motivation. 

PMID- 25595117
TI  - N-acetylcysteine in patients with COPD exacerbations associated with increased
      sputum.
AB  - BACKGROUND: N-acetylcysteine (NAC) has been shown not to alter the clinical
      outcome in chronic obstructive pulmonary disease (COPD) exacerbations. However,
      NAC may improve symptoms through its mucolytic effect in the subgroup of patients
      with increased sputum production. The aims of this study were to determine
      whether NAC improves symptoms and pulmonary function in patients with COPD
      exacerbation and increased sputum production. METHODS: This was a placebo
      controlled study, where patients with severe COPD and increased sputum
      production, who were hospitalized for an exacerbation, were included. They were
      randomized to receive either NAC 200 mg tid or placebo in addition to the usual
      treatment. RESULTS: Forty-two patients were included and were equally distributed
      to NAC and placebo groups. The symptoms, namely, ease of sputum production and
      dyspnea at rest and on exertion significantly improved in both groups; but there
      was no difference in improvement between NAC and placebo groups (p = 0.96, 0.62,
      0.31, respectively). Similarly, forced expiratory volume-one second (FEV1) and
      PaO2 levels improved significantly in NAC (964 +/- 599-1239 +/- 543 ml, p <
      0.001, and 57.5 +/- 14.5-70.5 +/- 16.0 mmHg, p < 0.001, respectively) and placebo
      groups (981 +/- 514-1180 +/- 535 ml, p < 0.001 and 57.9 +/- 14.3-68.7 +/- 19.0
      mmHg, p < 0.001, respectively), without any difference between the two groups (p
      = 0.52 and 0.57). There was no difference in the number of exacerbations during
      the 6-month follow-up period. CONCLUSION: NAC does not have any beneficial effect
      on clinical outcomes in patients with severe COPD exacerbation associated with
      increased and/or viscous mucus production.

PMID- 25595116
TI  - Level of knowledge about glaucoma in Vienna.
AB  - BACKGROUND: Glaucoma is a chronic and serious disease calling for consistent
      lifelong therapy. The patient's compliance requires that he/she be well informed
      about the disease. The purpose of the present study was to determine the level of
      knowledge about glaucoma, and compare young patients with older ones as well as
      glaucoma patients with nonglaucoma ones. METHODS: A total of 1110 questionnaires
      were distributed to patients and their relatives at the outpatient eye clinic of
      Hietzing Hospital (Vienna), of which 1041 were returned. The questionnaire
      comprised 18 questions. Patients were divided into two groups: group 1 consisted
      of those aged 18-60 years, while group 2 consisted of those older than 61 years.
      RESULTS: In total, 941 questionnaires were evaluated; 72.8% of the respondents
      were older than 60 years, and one-half of the respondents had glaucoma (51%). The
      majority of patients had "moderate knowledge" of the disease (41.87%), followed
      by "poor knowledge" (32.52%). Glaucoma patients had considerably better knowledge
      of the disease (p < 0.01) than did nonglaucoma patients. Younger patients were
      significantly better informed than older ones (p < 0.01). Nonglaucoma patients
      with a positive diagnosis of glaucoma among their circle of friends or family
      were significantly better informed (p < 0.01) than those without such persons in
      their circle of friends. CONCLUSION: Persons with glaucoma are much better
      informed about the disease than nonglaucoma patients, but the general level of
      knowledge is very low. Notably, younger patients were better informed than older
      ones. The present study, comprising a large number of patients, revealed poor
      knowledge of glaucoma among patients with the disease and especially among
      nonglaucoma patients in Vienna.

PMID- 25595121
TI  - Na(+)/H(+) exchanger in the regulation of platelet activation and paradoxical
      effects of cariporide.
AB  - Platelets are anucleated cell fragments derived from mature megakaryocytes and
      function in hemostasis when the endothelium is injured. Hemostasis involving
      platelets can be divided into four phases: adhesion, activation, secretion, and
      aggregation. Platelet activation requires a rise in intracellular Ca(2+)
      concentrations and results in both a morphological change and the secretion of
      platelet granule contents. Na(+)/H(+) exchanger isoform 1 (NHE1) regulates the
      intracellular pH (pHi) and the volume of platelets. In addition, NHE1 plays a
      large role in platelet activation. Thrombus generation involves NHE1 activation
      and an increase in [Ca(2+)]i, which results from NHE1-mediated Na(+) overload and
      the reversal of the Na(+)/Ca(2+) exchanger. Cariporide (HOE-642), a potent NHE1
      inhibitor, has inhibitory effects on the degranulation of human platelets, the
      formation of platelet-leukocyte-aggregates, and the activation of the GPIIb/IIIa
      receptor (PAC-1). However, despite the demonstrated protection against myocardial
      infarction as mediated by cariporide in patients undergoing coronary artery
      bypass graft surgery, the EXPEDITION clinical trial revealed that cariporide
      treatment increased mortality due to thromboembolic stroke. These findings
      suggest that a better understanding of NHE1 and its effect on platelet function
      and procoagulant factor regulation is warranted in order to develop therapies
      using NHE inhibitors. 

PMID- 25595122
TI  - Transferrin and thyroid hormone converge in the control of myelinogenesis.
AB  - Myelination is a concerted mechanism tightly regulated in the brain. Although
      several factors are known to participate during this process, the complete
      sequence of events is far from being fully elucidated. Separate effects of
      apotransferrin (aTf) and thyroid hormone (TH) are well documented on rat myelin
      formation. TH promotes the maturation of oligodendrocyte progenitors (OPCs) into
      myelinating oligodendrocytes (OLGs), while aTf is able to induce the commitment
      of neural stem cells (NSCs) toward the oligodendroglial linage and favors OLG
      maturation. We have also demonstrated that Tf mRNA exhibited a seven-fold
      increase in hyperthyroid animals. These observations have led us to hypothesize
      that both factors may interplay during oligodendrogenesis. To assess the combined
      effects of aTf and TH on proper myelination in the rat brain, Tf expression and
      oligodendroglial maturation were evaluated at postnatal days 10 (P10) and 20
      (P20) in several experimental groups. At P10, an up-regulation of both Tf mRNA
      and protein, as well as myelination, was found in hyperthyroid animals, while a
      decrease in Tf mRNA levels and myelin formation was detected in the hypothyroid
      group. At P20, no differences were found either in Tf mRNA or protein levels
      between hyperthyroid and control (Ctrol) rats, although differences in OLG
      differentiation remained. Also at P20, hypothyroid animals showed decreased Tf
      mRNA and protein levels accompanied with a less mature myelinating phenotype.
      Moreover, TH and aTf differentially regulate the expression of KLF9 transcription
      factor as well as TRalpha and TRbeta at P10 and P20. Our results suggest that TH
      is necessary early in OLG development for aTf action, as exogenous aTf
      administration was unable to counteract the effect of low TH levels in the
      hypothyroid state in all the time points analyzed. Furthermore, the fact that
      hyperthyroidism induced an increase in Tf expression and aTf-dependent regulation
      of TRalpha strongly suggests that Tf could be involved in some of TH later
      effects on OLG maturation. Here we describe the possible relationship between TH
      and aTf and its implication in oligodendrogenesis. 

PMID- 25595125
TI  - Solid-state interactions at the core-coat interface: physicochemical
      characterization of enteric-coated omeprazole pellets without a protective sub
      coat.
AB  - Conventionally, scanning electron or transmission microscopy, Raman and near
      infrared (NIR) spectroscopy, terahertz, florescence, and nuclear magnetic
      resonance imaging have been used to characterize functional coating structure.
      This study highlights the use of fluorescence microscopy to investigate the
      physicochemical stability and coating integrity of the commercially available
      enteric-coated omeprazole pellets containing a basic excipient and prepared by
      extrusion and spheronization or drug layering on the nonpareil seed, immediately
      followed by enteric coating (i.e., absence of protective sub-coat). The nature of
      coating interface and the likely development of an in situ interfacial layer
      after the application of enteric coating solution was examined using HPLC, NMR,
      differential scanning calorimetry (DSC), and fluorescent imaging methods.
      Likewise for the characterization of the solid pellet structure via fluorescence
      microscopy, a new approach based on fracturing technique (to avoid surface
      contamination) rather than microtome sectioning was used and validated.
      Analytical data showed that the pellets containing omeprazole remained chemically
      stable (>99.5% recovered). Control of the microenvironmental pH by the addition
      of alkalinizing excipient within a core formulation or as part of drug layering
      on top of nonpareil seed appears to efficiently neutralize the acidic effect of
      enteric coating dispersion. Fluorescence images further illustrate the absence of
      any discernable in situ layer formation at the coat-core interface. 

PMID- 25595123
TI  - Mitigation of infectious disease at school: targeted class closure vs school
      closure.
AB  - BACKGROUND: School environments are thought to play an important role in the
      community spread of infectious diseases such as influenza because of the high
      mixing rates of school children. The closure of schools has therefore been
      proposed as an efficient mitigation strategy. Such measures come however with
      high associated social and economic costs, making alternative, less disruptive
      interventions highly desirable. The recent availability of high-resolution
      contact network data from school environments provides an opportunity to design
      models of micro-interventions and compare the outcomes of alternative mitigation
      measures. METHODS AND RESULTS: We model mitigation measures that involve the
      targeted closure of school classes or grades based on readily available
      information such as the number of symptomatic infectious children in a class. We
      focus on the specific case of a primary school for which we have high-resolution
      data on the close-range interactions of children and teachers. We simulate the
      spread of an influenza-like illness in this population by using an SEIR model
      with asymptomatics, and compare the outcomes of different mitigation strategies.
      We find that targeted class closure affords strong mitigation effects: closing a
      class for a fixed period of time--equal to the sum of the average infectious and
      latent durations--whenever two infectious individuals are detected in that class
      decreases the attack rate by almost 70% and significantly decreases the
      probability of a severe outbreak. The closure of all classes of the same grade
      mitigates the spread almost as much as closing the whole school. CONCLUSIONS: Our
      model of targeted class closure strategies based on readily available information
      on symptomatic subjects and on limited information on mixing patterns, such as
      the grade structure of the school, shows that these strategies might be almost as
      effective as whole-school closure, at a much lower cost. This may inform public
      health policies for the management and mitigation of influenza-like outbreaks in
      the community.

PMID- 25595126
TI  - Patients with diabetes requiring emergency department care for hypoglycaemia:
      characteristics and long-term outcomes determined from multiple data sources.
AB  - AIM: To triangulate three data sources and report the characteristics and long
      term outcomes of patients with diabetes requiring emergency department (ED) care
      for hypoglycaemia. METHOD: Three data sources were used-ambulance electronic
      records, hospital episode statistics and patient administration system.
      Hypoglycaemia (capillary blood glucose <4.0 mmol/L)-related attendances to a
      single hospital's ED between 1 April 2012 and 31 March 2013 were studied.
      RESULTS: Using the three sources, there were 165 hypoglycaemia-related
      attendances in 132 patients with diabetes [type 1-59 episodes in 43 patients,
      type 2-106 episodes in 89 patients (therapy-54 (51%) insulin, 35 (33%)
      sulfonylurea, 11 (10%) both, 6 (6%) others)]. At best only 65% of episodes would
      have been identified were a single data source used. Patients with type 2 vs type
      1 diabetes were older (median age 79 vs 61 years, p<0.0001), had more
      comorbidities (median Charlson comorbidity index (CCI) 4 vs 3, p=0.002) but no
      difference in HbA1c (median 7.8% vs 8.4%, p=0.065). Compared with insulin-treated
      type 2 patients with diabetes, sulfonylurea-treated patients (33%) were older
      (median age 82 vs 76 years, p=0.007), had worse renal function (median estimated
      glomerular filtration rate 38 vs 56 mL/min/1.73 m(2), p=0.019) and lower HbA1c
      (median 6.7% vs 8.4%, p<0.0001). At least 17 (10%) hypoglycaemic episodes
      resulted in additional serious harm. The 30-day, 90-day and 1-year all-cause
      mortality were 10.6% (14), 16.7% (22) and 28% (37), respectively. Age, CCI and
      hospitalisation were risk factors for long-term mortality. CONCLUSIONS:
      Dependence on a single data source would have at best identified only 65% of
      episodes. One-third of episodes were sulfonylurea related in patients with type 2
      diabetes, and one-fourth of all patients with diabetes who required ED care for
      hypoglycaemia died the following year.

PMID- 25595127
TI  - Effect of low-level laser therapy (685 nm, 3 J/cm(2)) on functional recovery of
      the sciatic nerve in rats following crushing lesion.
AB  - Previous studies have shown that low-level laser therapy (LLLT) promotes
      posttraumatic nerve regeneration. The objective of the present study was to
      assess the efficacy of 685-nm LLLT at the dosage of 3 J/cm(2) in the functional
      recovery of the sciatic nerve in rats following crushing injury. The left sciatic
      nerves of 20 male Wistar rats were subjected to controlled crush injury by a
      hemostatic tweezers, and the rats were randomly allocated into two experimental
      groups as follows: control group and laser group. Laser irradiation (685 nm
      wavelength; 15 mW, CW, 3 J/cm(2), spot of 0.028 cm(2)) was started on the
      postsurgical first day, above the site of injury, and was continued for 21
      consecutive days. Functional recovery was evaluated at 3 weeks postoperatively by
      measuring the sciatic functional index (SFI) and sciatic static index (SSI) at
      weekly intervals. The treated rats showed improvement in motion pattern. The SFI
      and SSI results were significant when comparing two groups on the 14th and 21st
      postoperative days (p < 0.05). There were intra-group differences detected in
      laser group in different periods (p < 0.05). Low-level laser irradiation, with
      the parameters used in the present study, accelerated and improved sciatic nerve
      function in rats after crushing injury.

PMID- 25595128
TI  - Cocaine activates Rac1 to control structural and behavioral plasticity in caudate
      putamen.
AB  - Repeated exposure to cocaine was previously found to cause sensitized behavioral
      responses and structural remodeling on medium spiny neurons of the nucleus
      accumbens (NAc) and caudate putamen (CPu). Rac1 has emerged as a key integrator
      of environmental cues that regulates dendritic cytoskeletons. In this study, we
      investigated the role of Rac1 in cocaine-induced dendritic and behavioral
      plasticity in the CPu. We found that Rac1 activation was reduced in the NAc but
      increased in the CPu following repeated cocaine treatment. Inhibition of Rac1
      activity by a Rac1-specific inhibitor NSC23766, overexpression of a dominant
      negative mutant of Rac1 (T17N-Rac1) or local knockout of Rac1 attenuated the
      cocaine-induced increase in dendrites and spine density in the CPu, whereas
      overexpression of a constitutively active Rac1 exert the opposite effect.
      Moreover, NSC23766 reversed the increased number of asymmetric spine synapses in
      the CPu following chronic cocaine exposure. Downregulation of Rac1 activity
      likewise attenuates behavioral reward responses to cocaine exposure, with
      activation of Rac1 producing the opposite effect. Thus, Rac1 signaling is
      differentially regulated in the NAc and CPu after repeated cocaine treatment, and
      induction of Rac1 activation in the CPu is important for cocaine exposure-induced
      dendritic remodeling and behavioral plasticity. 

PMID- 25595130
TI  - Impact of information technology on information gaps in canadian ambulatory care
      encounters.
AB  - BACKGROUND: Specialist physicians require clinical information for patient visits
      in ambulatory encounters, some of which they may access via digital health
      solutions. OBJECTIVE: This study explored the completeness of information for
      patient care and the consequences of gaps for ambulatory specialist services
      provided in ambulatory settings in Canada. METHODS: A sample of specialist
      physicians practising in outpatient clinics was recruited from a health care
      provider research panel. The study (n=1800 patient encounters) looked at the
      completeness of patient information experienced by physicians who work in
      environments with rich health information exchange (Connected) and a comparison
      cohort with less information available electronically (Unconnected). RESULTS:
      Unconnected physicians were significantly more likely to be missing information
      they needed for patient encounters (13% of encounters for Unconnected physicians
      vs 7% for Connected physicians). Unconnected physicians were also more likely to
      report that missing information had consequences (23% vs 13% of encounters). Lab
      results were the most common type of patient information missing for both
      Unconnected and Connected specialists (25% for Unconnected physicians vs 11%
      Connected physicians). CONCLUSIONS: The results from this study indicate that
      Canadian physicians commonly experience information gaps in ambulatory
      encounters, and that many of these gaps are of consequence to themselves, their
      patients, and the healthcare system. Wasting physician and patient time, as well
      as being forced to proceed with incomplete information, were the most common
      consequences of information gaps reported.

PMID- 25595129
TI  - Feasibility of functional neuroimaging to understand adolescent women's sexual
      decision making.
AB  - PURPOSE: For young women, new sexual experiences normatively increase after
      puberty and coincide with extensive changes to brain regions governing self
      regulation of risk behavior. These neurodevelopmental changes could leave some
      young women vulnerable for negative sexual outcomes, including sexually
      transmitted infection and unintended pregnancy. We evaluated the feasibility of
      using functional neuroimaging to understand the sexual decision making of
      adolescent women. METHODS: Adolescent women (N = 14; 14-15 years) completed
      enrollment interviews, a neuroimaging task gauging neural activation to
      appetitive stimuli, and 30 days of prospective diaries following the scan
      characterizing daily affect and sexual behaviors. Descriptive and inferential
      statistics assessed the association between imaging and behavioral data. RESULTS:
      Young women were highly compliant with neuroimaging and diary protocol. Neural
      activity in a cognitive-affective network, including prefrontal and anterior
      cingulate regions, was significantly greater during low-risk decisions. Compared
      with other decisions, high-risk sexual decisions elicited greater activity in the
      anterior cingulate, and low-risk sexual decision elicited greater activity in
      regions of the visual cortex. Young women's sexual decision ratings were linked
      to their sexual history characteristics and daily self-reports of sexual emotions
      and behaviors. CONCLUSIONS: It is feasible to recruit and retain a cohort of
      female participants to perform a functional magnetic resonance imaging task
      focused on making decisions about sex, on the basis of varying levels of
      hypothetical sexual risk, and to complete longitudinal prospective diaries
      following this task. Preliminary evidence suggests that risk level differentially
      impacts brain activity related to sexual decision making in these women, which
      may be related to past and future sexual behaviors.

PMID- 25595131
TI  - Dose calculation accuracy of different image value to density tables for cone
      beam CT planning in head & neck and pelvic localizations.
AB  - PURPOSE: We aimed to identify the most accurate combination of phantom and
      protocol for image value to density table (IVDT) on volume-modulated arc therapy
      (VMAT) dose calculation based on kV-Cone-beam CT imaging, for head and neck (H&N)
      and pelvic localizations. METHODS: Three phantoms (Catphan((r))600, CIRS((r))062M
      (inner phantom for head and outer phantom for body), and TomoTherapy((r))
      "Cheese" phantom) were used to create IVDT curves of CBCT systems with two
      different CBCT protocols (Standard-dose Head and Standard Pelvis). Hounsfield
      Unit (HU) time stability and repeatability for a single On-Board-Imager (OBI) and
      compatibility of two distinct devices were assessed with Catphan((r))600. Images
      from the anthropomorphic phantom CIRS ATOM((r)) for both CT and CBCT modalities
      were used for VMAT dose calculation from different IVDT curves. Dosimetric
      indices from CT and CBCT imaging were compared. RESULTS: IVDT curves from CBCT
      images were highly different depending on phantom used (up to 1000 HU for high
      densities) and protocol applied (up to 200 HU for high densities). HU time
      stability was verified over seven weeks. A maximum difference of 3% on the dose
      calculation indices studied was found between CT and CBCT VMAT dose calculation
      across the two localizations using appropriate IVDT curves. One IVDT curve per
      localization can be established with a bi-monthly verification of IVDT-CBCT.
      CONCLUSIONS: The IVDT-CBCTCIRS-Head phantom with the Standard-dose Head protocol
      was the most accurate combination for dose calculation on H&N CBCT images. For
      pelvic localizations, the IVDT-CBCTCheese established with the Standard Pelvis
      protocol provided the best accuracy.

PMID- 25595132
TI  - Carbon monoxide increases inducible NOS expression that mediates CO-induced
      myocardial damage during ischemia-reperfusion.
AB  - We investigated the role of inducible nitric oxide (NO) synthase (iNOS) on
      ischemic myocardial damage in rats exposed to daily low nontoxic levels of carbon
      monoxide (CO). CO is a ubiquitous environmental pollutant that impacts on
      mortality and morbidity from cardiovascular diseases. We have previously shown
      that CO exposure aggravates myocardial ischemia-reperfusion (I/R) injury partly
      because of increased oxidative stress. Nevertheless, cellular mechanisms
      underlying cardiac CO toxicity remain hypothetical. Wistar rats were exposed to
      simulated urban CO pollution for 4 wk. First, the effects of CO exposure on NO
      production and NO synthase (NOS) expression were evaluated. Myocardial I/R was
      performed on isolated perfused hearts in the presence or absence of S-methyl
      isothiourea (1 MUM), a NOS inhibitor highly specific for iNOS. Finally, Ca(2+)
      handling was evaluated in isolated myocytes before and after an anoxia
      reoxygenation performed with or without S-methyl-isothiourea or N-acetylcystein
      (20 MUM), a nonspecific antioxidant. Our main results revealed that 1) CO
      exposure altered the pattern of NOS expression, which is characterized by
      increased neuronal NOS and iNOS expression; 2) cardiac NO production increased in
      CO rats because of its overexpression of iNOS; and 3) the use of a specific
      inhibitor of iNOS reduced myocardial hypersensitivity to I/R (infarct size, 29
      vs. 51% of risk zone) in CO rat hearts. These last results are explained by the
      deleterious effects of NO and reactive oxygen species overproduction by iNOS on
      diastolic Ca(2+) overload and myofilaments Ca(2+) sensitivity. In conclusion,
      this study highlights the involvement of iNOS overexpression in the pathogenesis
      of simulated urban CO air pollution exposure.

PMID- 25595133
TI  - Endothelial-binding, proinflammatory T cells identified by MCAM (CD146)
      expression: Characterization and role in human autoimmune diseases.
AB  - A subset of T cells defined by the cell surface expression of MCAM (CD146) has
      been identified in the peripheral circulation of healthy individuals. These cells
      comprise approximately 3% of the pool of circulating T cells, have an effector
      memory phenotype, and are capable of producing several cytokines. Notably, the
      MCAM positive cells are enhanced for IL-17 production compared to MCAM negative
      effector memory T cells. These cells are committed to IL-17 production and do not
      require in vitro polarization with exogenous cytokines. MCAM positive T cells
      also demonstrate an increased ability to bind to endothelial monolayers. In
      numerous autoimmune diseases these cells are found at increased proportions in
      the peripheral circulation, and at the sites of active inflammation in patients
      with autoimmune disease, these cells appear in large numbers and are major
      contributors to IL-17 production. Studies to date have been performed with human
      subjects and it is uncertain if appropriate mouse models exist for this cell
      type. These cells could represent early components of the adaptive immune
      response and serve as targets of therapy in these diseases, although much work
      remains to be performed in order to discern the exact nature and function of
      these cells.

PMID- 25595134
TI  - Automated synthesis and PET evaluation of both enantiomers of [18F]FMISO.
AB  - INTRODUCTION: [(18)F]FMISO, the widely used positron emission tomography (PET)
      hypoxia tracer, is a chiral compound clinically used as a racemic mixture. The
      purpose of this study was to synthesize the individual (R)- and the (S)-
      enantiomers of [(18)F]FMISO and compare their PET imaging characteristics.
      METHODS: The radiosynthesis of enantiopure (R)- and (S)-[(18)F]FMISO was based on
      Co(salen) (N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt)
      mediated opening of enantiopure epoxides with [(18)F]HF. The uptake and clearance
      of the individual [(18)F]FMISO antipodes were investigated using micro-PET/CT
      imaging performed on mice bearing FaDu tumors. Image-derived biodistribution was
      obtained from micro-PET/CT scans performed at 1 and 3 hours post injection
      (p.i.). In addition, the uptake patterns of each enantiomer were observed using
      two-hour dynamic micro-PET/CT scans, and the time-activity curves from different
      organs were compared. RESULTS: The individual (R)- and (S)-[(18)F]FMISO
      enantiomers were synthesized in one step with high enantiomeric excess (ee)>99%
      and radiochemical purity>97% using custom-made automation module. The dynamic
      micro-PET/CT scanning revealed a faster initial uptake of the (R)-[(18)F]FMISO
      enantiomer in tumor and muscle tissues, however the difference became
      progressively smaller with time. The tumor-to-muscle (T/M) and tumor-to-liver
      (T/L) ratios remained nearly identical for the (R)- and (S)-forms at all time
      points. The micro-PET/CT imaging at 1 and 3 hours p.i. did not show any
      significant enantioselective tissue uptake. CONCLUSIONS: Although the (R)
      enantiomer of [(18)F]FMISO demonstrated a somewhat faster initial tumor and
      muscle uptake no significant enantioselective tissue uptake was observed at later
      time points. The T/M- and T/L- ratios for the (R)- and (S)-forms were the same
      within the experimental error at all times. Therefore, the use of enantiopure
      [(18)F]FMISO is unlikely to present any practical clinical benefit for PET
      imaging.

PMID- 25595135
TI  - Prognostic value of positron emission tomography-assessed tumor heterogeneity in
      patients with thyroid cancer undergoing treatment with radiopeptide therapy.
AB  - INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) is a treatment option
      for both iodine-refractory differentiated and advanced medullary thyroid cancer
      (TC). It requires over-expression of somatostatin receptor subtype II (SSTR) that
      can be non-invasively assessed by positron emission tomography (PET). Assessment
      of tumor heterogeneity is increasingly used as a tool for prognostication
      prediction. We investigated the potential of SSTR-PET to assess intraindividual
      tumor heterogeneity and thereby treatment response prior to PRRT. METHODS: 12
      patients with progressive radioiodine-refractory differentiated (1 papillary, 1
      oxyphilic, 2 oncocytic, 4 follicular) or medullary (n=4) TC were enrolled. SSTR
      PET was performed at baseline. Conventional PET parameters and heterogeneity
      parameters were analyzed regarding their potential to predict progression-free
      (PFS, mean, 221 days) and overall survival (OS, mean, 450 days). Parameters of a
      subgroup of lesions (n=23) were also correlated with morphological response
      according to modified RECIST criteria. RESULTS: In patient-based analysis, all
      conventional parameters failed to predict PFS. Several textural parameters showed
      a significant capability to assess PFS. Thereby, "Grey level non uniformity" had
      the highest area under the curve (AUC, 0.93) in Receiver operating
      characteristics analysis followed by "Contrast" (AUC, 0.89). In lesion-based
      analysis, only "Entropy" revealed potential to evaluate disease progression. OS
      could not be assessed by any parameter investigated. CONCLUSIONS: Tumor
      heterogeneity seems to be a predictor of response to PRRT in patients with iodine
      refractory differentiated/advanced medullary thyroid cancer and outperforms
      conventional PET parameters like standardized uptake value. In a "theranostic"
      approach, assessment of textural parameters may help in selecting patients who
      might benefit from PRRT.

PMID- 25595136
TI  - Preventing brain disorders: a framework for action.
AB  - INTRODUCTION: Prevention efforts have greatly reduced the prevalence of many
      communicable and non-communicable diseases worldwide. In contrast, prevention
      strategies for mental disorders remain in their infancy. This paper provides a
      summary of the key issues surrounding mental disorder prevention and proposes a
      framework for how to catalyze action in the area. MATERIALS AND METHODS: Three
      core assumptions guide this work (1) the onset of mental disorders is often
      preventable, (2) among those individuals with a mental disorder, the trajectory
      of health and functioning can be shaped by external resources, and (3) many
      specific and generic risk and protective factors for mental disorders are
      associated with specific stages of the life course. CONCLUSION: We propose that
      the adoption of a life course approach to prevention can be clarifying and
      motivating for both research and practice.

PMID- 25595137
TI  - A validated LC-MS-MS method for simultaneous identification and quantitation of
      rodenticides in blood.
AB  - A rapid, highly sensitive and specific analytical method for the extraction,
      identification and quantification of nine rodenticides from whole blood has been
      developed and validated. Commercially available rodenticides in Australia include
      coumatetralyl, warfarin, brodifacoum, bromadiolone, difenacoum, flocoumafen,
      difethialone, diphacinone and chlorophacinone. A Waters ACQUITY UPLC TQD system
      operating in multiple reaction monitoring mode was used to conduct the analysis.
      Two different ionization techniques, ES+ and ES-, were examined to achieve
      optimal sensitivity and selectivity resulting in detection by MS-MS using
      electrospray ionization in positive mode for difenacoum and brodifacoum and in
      negative mode for all other analytes. All analytes were extracted from 200 uL of
      whole blood with ethylacetate and separated on a Waters ACQUITY UPLC BEH-C18
      column using gradient elution. Ammonium acetate (10 mM, pH 7.5) and methanol were
      used as mobile phases with a total run time of 8 min. Recoveries were between 70
      and 105% with limits of detection ranging from 0.5 to 1 ng/mL. The limit of
      quantitation was 2 ng/mL for all analytes. Calibration curves were linear within
      the range 2-200 ng/mL for all analytes with the coefficient of determination
      >=0.98. The application of the proposed method using liquid-liquid extraction in
      a series of clinical investigations and forensic toxicological analyses was
      successful. 

PMID- 25595138
TI  - Atorvastatin in combination with inhaled beclometasone modulates inflammatory
      sputum mediators in smokers with asthma.
AB  - BACKGROUND: Statins have pleiotropic immunomodulatory effects that may be
      beneficial in the treatment of asthma. We previously reported that treatment with
      atorvastatin improved asthma symptoms in smokers with asthma in the absence of a
      change in the concentration of a selection of sputum inflammatory mediators.
      OBJECTIVE: To determine the effects of atorvastatin alone and in combination with
      inhaled corticosteroid on a range of sputum cytokines, chemokines and growth
      factors implicated in the pathogenesis of asthma, and their association with
      asthma control questionnaire (ACQ) and/or asthma quality of life questionnaire
      (AQLQ) scores. METHODS: Sputum samples were analysed from a sub-group of 39
      smokers with mild to moderate asthma recruited to a randomised controlled trial
      comparing atorvastatin (40 mg/day) versus placebo for four weeks, followed by
      inhaled beclometasone (400 MUg/day) for a further four weeks. Induced sputum
      supernatant fluid was analysed (Luminex or biochemical analyses) for
      concentrations of 35 mediators. RESULTS: Sputum mediator concentrations were not
      reduced by inhaled beclometasone alone. Atorvastatin significantly reduced sputum
      concentrations of CCL7, IL-12p70, sCD40L, FGF-2, CCL4, TGF-alpha and MMP-8
      compared with placebo and, when combined with inhaled beclometasone, reduced
      sputum concentrations of MMP-8, IL-1beta, IL-10, MMP-9, sCD40L, FGF-2, IL-7, G
      CSF and CCL7 compared to ICS alone. Improvements in ACQ and/or AQLQ scores with
      atorvastatin and ICS were associated with decreases in G-CSF, IL-7, CCL2 and
      CXCL8. CONCLUSION: Short-term treatment with atorvastatin alone or in combination
      with inhaled beclometasone reduces several sputum cytokines, chemokines and
      growth factors concentrations unresponsive to inhaled corticosteroids alone, in
      smokers with asthma.

PMID- 25595139
TI  - Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis.
AB  - BACKGROUND: Dabigatran and rivaroxaban are new oral anticoagulants that are
      eliminated through the kidneys. Their use in dialysis patients is discouraged
      because these drugs can bioaccumulate to precipitate inadvertent bleeding. We
      wanted to determine whether prescription of dabigatran or rivaroxaban was
      occurring in the dialysis population and whether these practices were safe.
      METHODS AND RESULTS: Prevalence plots were used to describe the point prevalence
      (monthly) of dabigatran and rivaroxaban use among 29977 hemodialysis patients
      with atrial fibrillation. Poisson regression compared the rate of bleeding,
      stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or
      warfarin. The first record of dabigatran prescription among hemodialysis patients
      occurred 45 days after the drug became available in the United States. Since
      then, dabigatran and rivaroxaban use in the atrial fibrillation-end-stage renal
      disease population has steadily risen where 5.9% of anticoagulated dialysis
      patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson
      regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21-1.81;
      P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03-1.83;
      P=0.04) associated with a higher risk of hospitalization or death from bleeding
      when compared with warfarin. The risk of hemorrhagic death was even larger with
      dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18-2.68; P=0.006) and
      rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94-3.12; P=0.07)
      relative to warfarin. There were too few events in the study to detect meaningful
      differences in stroke and arterial embolism between the drug groups. CONCLUSIONS:
      More dialysis patients are being started on dabigatran and rivaroxaban, even when
      their use is contraindicated and there are no studies to support that the
      benefits outweigh the risks of these drugs in end-stage renal disease.

PMID- 25595140
TI  - Effect on laryngeal adductor function of vincristine block of posterior
      cricoarytenoid muscle 3 to 5 months after recurrent laryngeal nerve injury.
AB  - OBJECTIVES: It has been shown in a canine model that a single injection of
      vincristine into the posterior cricoarytenoid (PCA) muscle at the time of
      recurrent laryngeal nerve (RLN) injury effectively blocks its reinnervation and
      results in improved adductor strength. But clinically, such injuries are usually
      diagnosed weeks or months after onset. Vincristine injection does not affect a
      muscle that is already innervated; thus, there is a limited time frame following
      RLN injury during which a vincristine injection could effectively improve
      ultimate laryngeal adductor functional recovery. A series of delayed injections
      was performed in a canine model and results assessed. STUDY DESIGN: Animal
      (canine) experiment. METHODS: The RLN was transected and repaired, and
      vincristine (0.4 mg) was injected into the PCA muscle at the time of injury
      (n=12) or 3, 4, and 5 months later (n=8 each study group). Six months after RLN
      injury, laryngeal adductor function was measured. Results of vincristine
      injection without RLN injury (n=6) and longer-term (12 months) follow-up for time
      zero injections (n=4) are also reported. RESULTS: The animals injected at time
      zero had better adductor function than non-injected controls, as reported
      previously, and this result was further increased at 12 months. The 3-month delay
      gave results similar to the time zero group. The 5-month delay group showed no
      vincristine benefit, and the 4-month delay group gave an intermediate result.
      Vincristine to the PCA had no effect on adductor function when the RLN was left
      intact. Plasma levels showed 19% of injected vincristine reached systemic
      circulation, which was cleared within 69 hours. CONCLUSIONS: Vincristine
      injection of the PCA muscle after RLN injury, which blocks this antagonist muscle
      from synkinetic reinnervation, leads to improved laryngeal adductor functional
      recovery. The window of opportunity to apply this treatment closes by 4 months
      after RLN injury in the canine model. Human RLN recovery follows a similar time
      course and can reasonably be expected to have a similar therapeutic window.

PMID- 25595141
TI  - Craniofacial Surgery and Adverse Outcomes: An Inquiry Into Medical Negligence.
AB  - OBJECTIVE: This study aimed to evaluate factors contributing to medical
      negligence relevant to craniofacial surgery. METHODS: Retrospective analysis of
      verdict and settlement reports on the Westlaw legal database for outcome, awards,
      physician defendants, and other specific factors raised in malpractice
      litigation. RESULTS: Of 42 verdicts and settlement reports included, 52.4% were
      resolved with either an out-of-court settlement or plaintiff verdict, with
      aggregate payments totaling $50.1M (in 2013 dollars). Median settlements and jury
      awarded damages were $988,000 and $555,000, respectively. Payments in pediatric
      cases ($1.2M) were significantly higher. Plastic surgeons, oral surgeons, and
      otolaryngologists were the most commonly named defendants. The most common
      alleged factors included intraoperative negligence (69.0%), permanent deficits
      (54.8%), requiring additional surgery (52.4%), missed/delayed diagnosis of a
      complication (42.9%), disfigurement/scarring (28.6%), postoperative negligence
      (28.6%), and inadequate informed consent (20.6% of surgical cases). Failure to
      diagnose a fracture (19.0%) and cleft-reparative procedures (14.3%) were the most
      frequently litigated entities. CONCLUSION: Medical negligence related to
      craniofacial surgery involves plaintiffs in a wide age range as well as physician
      defendants in numerous specialties, and proceedings resolved with settlement and
      plaintiff verdict involve substantial payments. Cases with death, allegedly
      permanent injuries, and pediatric plaintiffs had significantly higher payments.

PMID- 25595142
TI  - Effect of a maternal and child health handbook on maternal knowledge and
      behaviour: a community-based controlled trial in rural Cambodia.
AB  - Maternal and child health (MCH) handbooks are comprehensive home-based booklets
      designed to integrate MCH records. Although empirical evidence suggests the
      handbooks are more effective than current card-type records, this has not been
      scientifically demonstrated. The objectives of this study were to evaluate the
      impact of the MCH handbook on maternal knowledge and behaviour as measured by
      antenatal care (ANC) attendance, delivery with skilled birth attendants (SBAs)
      and delivery at a health facility. The Cambodian version of the MCH handbook was
      developed and introduced in two health centres, and two other health centres
      served as controls. Pre-intervention and post-intervention surveys were conducted
      with 320 women from the intervention areas and 320 women from the control areas
      who had given birth within 1 year before the survey. We evaluated the impact of
      the handbook by using difference-in-differences (DID) analysis and calculated
      adjusted odds ratios for pre-post changes in key indicators by using logistic
      regression. In addition, we interviewed multiparous women, health staff and
      health volunteers to assess the acceptance and cultural appropriateness of the
      handbook. Content analysis was performed with the English-translated
      transcriptions. The DID analyses revealed that all key indicators increased in
      the intervention group against counterfactual assumptions. The intervention also
      increased maternal knowledge of all topics addressed except for the risk of
      severe bleeding after delivery; this may be attributable to the influence of
      cultural belief. Logistic regression showed that the intervention increased ANC
      attendance, delivery with SBAs and delivery at a health facility, even after
      adjusting for maternal age, education and economic conditions. The qualitative
      data indicated that the handbook was well received and culturally appropriate.
      Thus, the MCH handbook is a reasonable and superior alternative to current card
      type maternal records. 

PMID- 25595143
TI  - Breast cancer in the global south and the limitations of a biomedical framing: a
      critical review of the literature.
AB  - Public health researchers are devoting increasing attention to the growing burden
      of breast cancer in low-and middle-income countries (LMICs), previously thought
      to be minimally impacted by this disease. A critical examination of this body of
      literature is needed to explore the assumptions, advantages and limitations of
      current approaches. In our critical literature review, we find that researchers
      and public health practitioners predominantly privilege a biomedical perspective
      focused on patients' adherence (or non-adherence) to 'preventive' practices,
      screening behaviours and treatment regimens. Cost-effective 'quick fixes' are
      prioritized, and prevention is framed in terms of individual 'risk behaviours'.
      Thus, individuals and communities are held responsible for the success of the
      biomedical system; traditional belief systems and 'harmful' social practices are
      problematized. Inherently personal, social and cultural experiences of pain and
      suffering are neglected or reduced to the issue of chemical palliation. This
      narrow approach obscures the complex aetiology of the disease and perpetuates
      silence around power relations. This article calls for a social justice-oriented
      interrogation of the role of power and inequity in the global breast cancer
      epidemic, which recognizes the agency and experiences of women (and men) who
      experience breast cancer in the global south. 

PMID- 25595146
TI  - Speech dynamics are coded in the left motor cortex in fluent speakers but not in
      adults who stutter.
AB  - The precise excitability regulation of neuronal circuits in the primary motor
      cortex is central to the successful and fluent production of speech. Our question
      was whether the involuntary execution of undesirable movements, e.g. stuttering,
      is linked to an insufficient excitability tuning of neural populations in the
      orofacial region of the primary motor cortex. We determined the speech-related
      time course of excitability modulation in the left and right primary motor tongue
      representation. Thirteen fluent speakers (four females, nine males; aged 23-44)
      and 13 adults who stutter (four females, nine males, aged 21-55) were asked to
      build verbs with the verbal prefix 'auf'. Single-pulse transcranial magnetic
      stimulation was applied over the primary motor cortex during the transition phase
      between a fixed labiodental articulatory configuration and immediately following
      articulatory configurations, at different latencies after transition onset.
      Bilateral electromyography was recorded from self-adhesive electrodes placed on
      the surface of the tongue. Off-line, we extracted the motor evoked potential
      amplitudes and normalized these amplitudes to the individual baseline
      excitability during the fixed configuration. Fluent speakers demonstrated a
      prominent left hemisphere increase of motor cortex excitability in the transition
      phase (P = 0.009). In contrast, the excitability of the right primary motor
      tongue representation was unchanged. Interestingly, adults afflicted with
      stuttering revealed a lack of left-hemisphere facilitation. Moreover, the
      magnitude of facilitation was negatively correlated with stuttering frequency.
      Although orofacial midline muscles are bilaterally innervated from corticobulbar
      projections of both hemispheres, our results indicate that speech motor plans are
      controlled primarily in the left primary speech motor cortex. This speech motor
      planning-related asymmetry towards the left orofacial motor cortex is missing in
      stuttering. Moreover, a negative correlation between the amount of facilitation
      and stuttering severity suggests that we discovered a main physiological
      principle of fluent speech production and its role in stuttering. 

PMID- 25595145
TI  - Vascular and amyloid pathologies are independent predictors of cognitive decline
      in normal elderly.
AB  - Our primary objective was to investigate a biomarker driven model for the
      interrelationships between vascular disease pathology, amyloid pathology, and
      longitudinal cognitive decline in cognitively normal elderly subjects between 70
      and 90 years of age. Our secondary objective was to investigate the beneficial
      effect of cognitive reserve on these interrelationships. We used brain amyloid
      beta load measured using Pittsburgh compound B positron emission tomography as a
      marker for amyloid pathology. White matter hyperintensities and brain infarcts
      were measured using fluid-attenuated inversion recovery magnetic resonance
      imaging as a marker for vascular pathology. We studied 393 cognitively normal
      elderly participants in the population-based Mayo Clinic Study of Aging who had a
      baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging
      assessment, Pittsburgh compound B positron emission tomography scan, baseline
      cognitive assessment, lifestyle measures, and at least one additional clinical
      follow-up. We classified subjects as being on the amyloid pathway if they had a
      global cortical amyloid-beta load of >=1.5 standard uptake value ratio and those
      on the vascular pathway if they had a brain infarct and/or white matter
      hyperintensities load >=1.11% of total intracranial volume (which corresponds to
      the top 25% of white matter hyperintensities in an independent non-demented
      sample). We used a global cognitive z-score as a measure of cognition. We found
      no evidence that the presence or absence of vascular pathology influenced the
      presence or absence of amyloid pathology and vice versa, suggesting that the two
      processes seem to be independent. Baseline cognitive performance was lower in
      older individuals, in males, those with lower education/occupation, and those on
      the amyloid pathway. The rate of cognitive decline was higher in older
      individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P =
      0.0037) pathologies. In those subjects with both vascular and amyloid
      pathologies, the effect of both pathologies on cognition was additive and not
      synergistic. For a 79-year-old subject, the predicted annual rate of global z
      score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, 
      0.08 if on the amyloid pathway and -0.13 if on both pathways. The main
      conclusions of this study were: (i) amyloid and vascular pathologies seem to be
      at least partly independent processes that both affect longitudinal cognitive
      trajectories adversely and are major drivers of cognitive decline in the elderly;
      and (ii) cognitive reserve seems to offset the deleterious effect of both
      pathologies on the cognitive trajectories. 

PMID- 25595147
TI  - Increased sleep need and daytime sleepiness 6 months after traumatic brain
      injury: a prospective controlled clinical trial.
AB  - Post-traumatic sleep-wake disturbances are common after acute traumatic brain
      injury. Increased sleep need per 24 h and excessive daytime sleepiness are among
      the most prevalent post-traumatic sleep disorders and impair quality of life of
      trauma patients. Nevertheless, the relation between traumatic brain injury and
      sleep outcome, but also the link between post-traumatic sleep problems and
      clinical measures in the acute phase after traumatic brain injury has so far not
      been addressed in a controlled and prospective approach. We therefore performed a
      prospective controlled clinical study to examine (i) sleep-wake outcome after
      traumatic brain injury; and (ii) to screen for clinical and laboratory predictors
      of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60
      included patients with first-ever traumatic brain injury were available for
      follow-up examinations. Six months after trauma, the average sleep need per 24 h
      as assessed by actigraphy was markedly increased in patients as compared to
      controls (8.3 +/- 1.1 h versus 7.1 +/- 0.8 h, P < 0.0001). Objective daytime
      sleepiness was found in 57% of trauma patients and 19% of healthy subjects, and
      the average sleep latency in patients was reduced to 8.7 +/- 4.6 min (12.1 +/-
      4.7 min in controls, P = 0.0009). Patients, but not controls, markedly
      underestimated both excessive sleep need and excessive daytime sleepiness when
      assessed only by subjective means, emphasizing the unreliability of self
      assessment of increased sleep propensity in traumatic brain injury patients. At
      polysomnography, slow wave sleep after traumatic brain injury was more
      consolidated. The most important risk factor for developing increased sleep need
      after traumatic brain injury was the presence of an intracranial haemorrhage. In
      conclusion, we provide controlled and objective evidence for a direct relation
      between sleep-wake disturbances and traumatic brain injury, and for clinically
      significant underestimation of post-traumatic sleep-wake disturbances by trauma
      patients. 

PMID- 25595148
TI  - Developing a Culturally Sensitive Lifestyle Behavior Change Program for Older
      Latinas.
AB  - Despite the burgeoning U.S. Latino population and their increased risk of chronic
      disease, little emphasis had been placed on developing culturally sensitive
      lifestyle interventions in this area. This article examines older Latinas'
      sociocultural context relative to health with the goal of developing a culturally
      sensitive health behavior intervention. Photo-elicitation indicated two emerging
      themes that influenced lifestyle choices: family caregiving and religion.
      Researchers partnered with a faith-based organization to develop and implement a
      6-month lifestyle intervention for Latinas ages 50 and older: Abuelas en Accion
      (AEA). At completion, interviews were conducted to understand women's experiences
      and the influence AEA had on their lifestyles and health. Findings suggest that
      religious content empowered and deeply affected women; however, the
      intergenerational content presented significant challenges for instruction,
      retention, and implementation. We discuss findings in relation to the health
      intervention literature and provide suggestions for future interventions drawing
      on religion, family, and health behavior change. 

PMID- 25595150
TI  - Media Discourse on the Social Acceptability of Fecal Transplants.
AB  - Advances in human microbiome research have generated considerable interest in
      elucidating the role of bacteria in health and the application of microbial
      ecosystem therapies and probiotics. Fecal transplants involve the introduction of
      gut microbes from a healthy donor's stool to the patient and have been documented
      as effective for treating Clostridium difficile infections (CDIs) and some other
      gastrointestinal disorders. However, the treatment has encountered regulatory
      hurdles preventing widespread uptake. We examined dominant representations of
      fecal transplants in Canadian media and found that fecal transplants are often
      represented as being inherently disgusting or distasteful (the "ick factor").
      This "ick factor" is used to construct different messages about the treatment's
      social acceptability and legitimacy. We conclude that an over-emphasis on the
      "ick factor" constrains public discourse from a more nuanced discussion of the
      social challenges, scientific concerns, and regulatory issues surrounding the
      treatment. 

PMID- 25595149
TI  - HIV Treatment for Alcohol and Non-Injection Drug Users in El Salvador.
AB  - Since the mid-1990 s, many developing countries have introduced and expanded the
      availability of combination antiretroviral therapy (cART) to persons living with
      HIV (PLH). However, AIDS-related mortality continues to be high particularly
      among drug users. In this article, we present results from in-depth interviews
      with 13 HIV medical providers and 29 crack cocaine and alcohol using PLH in El
      Salvador. Providers endorsed negative attitudes toward substance using PLH and
      warned PLH that combining cART with drugs and alcohol would damage their livers
      and kidneys resulting in death. Upon diagnosis, PLH received little information
      about HIV treatment and many suffered depression and escalated their drug use.
      PLH reported suspending cART when they drank or used drugs because of providers'
      warnings. Substance using PLH were given few strategies and resources to quit
      using drugs. Messages from medical providers discourage drug users from
      initiating or adhering to antiretroviral therapy (ART) and may contribute to
      treatment abandonment.

PMID- 25595152
TI  - Theory of mind in behavioural-variant frontotemporal dementia and Alzheimer's
      disease: a meta-analysis.
AB  - Current evidence suggests that neurocognitive testing has limited practical
      benefit in distinguishing behavioural-variant frontotemporal dementia (bvFTD) and
      Alzheimer's disease (AD). In this meta-analysis of 30 studies, theory of mind
      (ToM) performances of 784 individuals with bvFTD (n=273) and AD (n=511) were
      compared with 671 healthy controls. ToM performances of 227 patients with bvFTD
      and 229 with AD were also compared in studies matched for general cognition. ToM
      was impaired in both bvFTD (d=1.79) and AD (d=1.15). In bvFTD, patients were
      particularly impaired in advanced tasks such as recognition of faux pas and
      sarcasm (d>2.0). In AD, ToM deficits were relatively modest. In studies matched
      for general cognition, ToM was significantly impaired in bvFTD in comparision to
      AD (d=1.29), especially for faux pas recognition (d=1.75). ToM dysfunction is a
      robust and more specific feature of bvFTD. In contrast, ToM deficits are modest
      compared with level of general cognitive impairment in AD. In both disorders,
      longer duration of disease and level of general cognitive impairment are related
      to relatively more severe ToM deficits. Assessment of ToM can be beneficial for
      early identification of bvFTD. 

PMID- 25595144
TI  - Consensus statement on management of dyslipidemia in Indian subjects.

PMID- 25595155
TI  - [Minimally Invasive Cardiac Surgery( MICS) through a Mini-right Thoracotomy].
AB  - Recently, the concept of minimally invasive surgery has been expanding in
      cardiothoracic surgery. Minimally invasive cadiac surgery( MICS) is characterized
      by the avoidance of full sternotomy and minimizing of surgical incision. The
      advantages of this approach include less postoperative discomfort and earlier
      mobilization and discharge. Since port-access cardiac surgery for atrial septal
      defect was performed in March 2005, we have improved the devices and procedure
      and actively applied port-access surgery to mitral valve disorders and various
      cardiac diseases. MICS patients were, on average, extubated sooner and discharged
      from the intensive care unit (ICU) and hospital earlier than coventional
      procedures patients. Additionally, MICS patients had less risk of receiving a
      blood transfusion. We believe recently advanced MICS is a very feasible surgical
      option, and that, in the near future, the MICS technique can be used for patients
      with a variety of preoperative backgrounds and more complex cardiovascular
      disorders. 

PMID- 25595153
TI  - Severe phenotypic spectrum of biallelic mutations in PRRT2 gene.
AB  - BACKGROUND: Heterozygous dominant mutations of PRRT2 have been associated with
      various types of paroxysmal neurological manifestations, including benign
      familial infantile convulsions and paroxysmal kinesigenic dyskinesia. The
      phenotype associated with biallelic mutations is not well understood as few cases
      have been reported. METHODS: PRRT2 screening was performed by Sanger sequencing
      and quantitative multiplex PCR of short fluorescent fragments. A CGH array was
      used to characterise the size of the deletion at the 16p11.2 locus. RESULTS: Five
      patients with homozygous or compound heterozygous deleterious PRRT2 gene
      mutations are described. These patients differ from those with a single mutation
      by their overall increased severity: (1) the combination of at least three
      different forms of paroxysmal neurological disorders within the same patient and
      persistence of paroxysmal attacks; (2) the occurrence of uncommon prolonged
      episodes of ataxia; and (3) the association of permanent neurological disorders
      including learning difficulties in four patients and cerebellar atrophy in 2.
      CONCLUSIONS: Our observations expand the phenotype related to PRRT2
      insufficiency, and highlight the complexity of the phenotype associated with
      biallelic mutations, which represents a severe neurological disease with various
      paroxysmal disorders and frequent developmental disabilities.

PMID- 25595154
TI  - [Introduction of Minimally Invasive Port-access Surgery for Aortic Valve
      Replacement;Yamagata University Hospital's Experience].
AB  - BACKGROUND: Minimally invasive cardiac surgery (MICS) through a small intercostal
      thoracotomy has many advantages, but it is still challenging because of limited
      mobility through the small skin incision and surgical field. The benefits of MICS
      should be reached without compromising the quality of the operation and
      increasing the morbidity and mortality of standard sternotomy approach. We have
      recently introduced MICS-aortic valve replacement (AVR) in order to establish as
      a standard surgical technique for the treatment of aortic insufficiency. METHODS:
      Eleven consecutive patients underwent MICS-AVR in Yamagata University Hospital.
      Anesthetic and surgical techniques were simplified and standardized as possible
      to overcome technical difficulties. Preoperative chest computed tomography( CT)
      provides useful information about suitability of the patient's anatomy for MICS
      approach. Furthermore, we developed a preoperative image overlay technique by
      projecting 3-dimensional CT image over the patient's body surface. RESULTS: There
      was no operative death. MICS-AVR procedure was completed in 10 patients. One
      patient was converted to sternotomy approach probably because of the vascular
      spasm through femoral artery cannulation for extracorporeal circulation. Although
      there were some anxious points to manage MICS procedure, preoperative planning
      based on the image overlay from CT image were useful for setup and instrument
      placement for MICS. CONCLUSIONS: MICS-AVR was introduced and safely performed
      with acceptable morbidity and excellent mortality at our institution. Close
      observation should be mandatory in order to implement individual and departmental
      performance monitoring with regard to the learning curves and surgical
      complications associated with less invasive procedure itself.

PMID- 25595157
TI  - [Effectiveness of Mitral Natural Folding Plasty for Minimally Invasive Cardiac
      Surgery Mitral Valve Plasty (MICS MVP)].
AB  - We performed 45 cases of Natural folding plasty without leaflet resection for
      degenerative mitral regurgitation (MR) between September 2005 and July 2014.
      Twenty cases of 45 were operated by right small intercostal approach (MICS).
      There was no operative mortality. No patient had greater than mild MR
      intraoperative transesophageal echocardiography. The median follow-up was 847
      (19~1,747) days. One case needed a second pump run performed without
      complication. One patient had a reoperation performed for recurrent MR 20 months
      later. Natural folding plasty for degenerative MR with favorable long term out
      come in our results. This technique is simple and reproducible for most surgeons.
      Furthermore, with its simplicity and reversibility, we considered it to be
      suitable for MICS approach. 

PMID- 25595156
TI  - [Early Results of Minimally Invasive Cardiac Surgery (MICS) Mitral Valve Surgery
      with 51 Cases].
AB  - BACKGROUND: Minimally invasive cardiac surgery of the mitral valve (MICS-MV) has
      become the routine approach to mitral valve disease in some centers. We reported
      early results of 51 cases of MICS-MV. METHOD: The preoperative variables,
      intraoperative date and postoperative outcomes of patients undergoing MICS-MV and
      conventional surgery of the mitral valve were collected from January 2013 to
      August 2014. RESULTS: Aortic cross clamp and cardio-pulmonary bypass( CPB) time
      were longer in this series than in the conventional median sternotomy. We
      experienced complications and 2 patients required mitral valve replacement (MVR)
      due to failure of repair in initial MICS cases. One case of the patients with
      infective endocarditis was performed conversion of from MICS to a median
      sternotomy due to left ventricle(LV) rupture. CONCLUSION: The early-time outcomes
      in these patients are acceptable. We think that large number of MICS-MV
      operations are required to overcome the learning curve.

PMID- 25595158
TI  - [Robot-assisted Mitral Valve Plasty].
AB  - In April 2014, Team Watanabe have completed 249 robot-assisted cardiac surgeries.
      Wide range of procedures include internal thoracic artery harvesting, totally
      endoscopic coronary artery bypass grafting(CABG), atrial septal defect closure,
      mitral valve plasty, cardiac tumor resection. The major benefit of robot-assisted
      cardiac surgery, which differentiates it from minimally invasive cardiac surgery,
      is that it only requires a few ports instead of small thoracotomy. Mitral valve
      plasty for regurgitation is one of the most suitable indication, which represents
      the advantage of robot-assisted cardiac surgery. The da Vinci surgical system
      completely changed the modality of cardiac surgeries from median sternotomy to
      endoscopic approach. Endoscopic surgery is expected not only to provide superior
      cosmesis but also to reduce complications and improve post-operative quality of
      life. In addition, we consider that sharing the same surgical view on the screen
      monitor is another great benefit from the educational point of view for the next
      generation.

PMID- 25595151
TI  - Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised,
      double blind, placebo controlled, phase III study.
AB  - OBJECTIVE: To assess the efficacy of recombinant human erythropoietin (rhEPO) in
      amyotrophic lateral sclerosis (ALS). METHODS: Patients with probable laboratory
      supported, probable or definite ALS were enrolled by 25 Italian centres and
      randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo
      fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The
      primary composite outcome was survival, tracheotomy or >23 h non-invasive
      ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC)
      and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing
      adverse events (AEs) causing withdrawal. The randomisation sequence was computer
      generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off
      score of 33) and onset (spinal or bulbar). The main outcome analysis was
      performed in all randomised patients and by intention-to-treat for the entire
      population and patients stratified by severity and onset. The study is
      registered, EudraCT 2009-016066-91. RESULTS: We randomly assigned 208 patients,
      of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became
      ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before
      receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for
      analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to
      0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI
      0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also
      after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was
      16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary
      outcomes. CONCLUSIONS: RhEPO 40,000 IU fortnightly did not change the course of
      ALS.

PMID- 25595159
TI  - [Endoscopic Long Saphenous Vein Harvest from Femoralsite to Below the Knee
      through a Single Small Incision for Minimally Invasive Coronary Artery Bypass
      Grafting].
AB  - BACKGROUND: Endoscopic saphenous vein harvest( EVH) for coronary artery bypass
      grafting( CABG) has been proved to be effective in reduced wound complications
      without compromising graft patency and mortality. Although EVH was usually
      performed from femoral site, we performed endoscopic long saphenous vein harvest(
      ELSH) from femoral to below the knee through a single small incision. There were
      few reports in EVH from below the knee and ELSH. PATIENTS AND METHODS: Between
      September 2012 and June 2014, 13 patients who underwent ELSH in CABG. We assessed
      the initial evaluation in ELSH using the VirtuoSaph system. ELSH was performed by
      our unified procedure protocol to harvest good saphenous vein graft. RESULTS: The
      success rate of ELSH was 100% (13/13). The harvest time was 83.6+/-15.2 min,
      graft length was 52.1+/-5.6 cm, and number of side branches requiring repair was
      2.6+/-1.6. Beating CABG was performed in all patients. The number of distal
      anastomoses was 3.8+/-0.8. Sequential bypass was 12 in total 23 saphenous vein
      grafts. The early patency was 95% (18/19 grafts) as evaluated by postoperative
      angiography or coronary enhanced computed tomography. All patients except 1(
      hospital death)were discharged without major or wound complications. CONCLUSIONS:
      The acceptable results and outcomes were demonstrated by our ELSH procedure
      protocol. ELSH is considered to be a feasible procedure to harvest enough graft
      length for 2 CABG and keep the other side of saphenous vein graft intact.

PMID- 25595160
TI  - [Clinical Results of Thoracic Endovascular Aortic Repair (TEVAR) for the
      Treatment of Aortic Arch Aneruysm].
AB  - Thoracic endovascular aortic repair( TEVAR) combined of neck branch
      reconstruction( debranching TEVAR:dTEVAR) is applied to aortic arch aneurysm for
      minimally invasive reduction and improvement of treatment results. We report the
      initial and long-term results of dTEVAR for the treatment of aortic arch
      aneurysm. TEVAR for zone 0-2 area was applied in 49 cases (Zone 0:1:2;8:5:36
      cases). Total dTEVAR was applied in zone 1 cases and 2 dTEVAR was performed in
      zone 2 cases. One dTEVAR or TEVAR with simple coverage of left subclavian artery
      was applied in zone 2 cases. Operative mortality within 30 days was 0% and there
      was 1 case in hospital death due to coronary arterial rupture after percutaneous
      coronary intervention. Perioperative morbidity included 1 case(2.0%) spinal cord
      ischemia, 4( 8.2%)arm claudication. In long-term follow-up, 5 cases died during
      the observation period (stroke in 1 case, heart failure in 1, neoplasma in 2,
      unknown in 1), but not in aortic rupture. Secondary type1 endoleak occurred in 2
      cases(4.1%). Graft occlusion for neck branch reconstruction was complicated with
      3 cases(6.1%), however no complications related to the graft occlusion. Our
      strategy of TEVAR provided durable results in patients treated for aortic arch
      aneurysm, with few adverse events. 

PMID- 25595161
TI  - [Thoracic Endovascular Aortic Repair (TEVAR) Combined with Embolization Technique
      for Saccular Aortic Arch Aneurysm].
AB  - Many of saccular aortic arch aneurysms exist near left subclabian artery(LSA).
      The thoracic endovascular aneurysm repair( TEVAR) landing on zone 2 is a less
      invasive and suitable procedure for this type of aneurysm. However, there are
      several cases with the aneurysm located close to LSA necessitate landing TEVAR on
      zone 1 or zone 0, otherwise the aneurysm could not be sealed completely. And this
      procedure seems to increase the invasiveness. In order to complete the sealing of
      the aneurysm and also keep the less invasiveness, we performed TEVAR using an
      axillo-axillary bypass or simple occlusion of LSA followed by an embolization
      using metal coil and NBCA through the catheter which detained in the saccular
      aneurysm beforehand. We report our experience of seven cases have been
      successfully treated by this procedure with good results. 

PMID- 25595162
TI  - [Complications of graft infection after endovascular aortic aneurysm repair].
AB  - OBJECTIVE: The endovascular approach to aortic aneurysm repair is widely
      spreading as an alternative to open repair. However infectious complications may
      be devastating. We described the experiences with infected aortic endografts and
      reviewed treatment and outcomes. METHODS: Eight patients were treated due to
      infected aortic endografts between June 2008 and March 2014. Seven males and 1
      female with median age of 66 years( range, 38-84years) had 5 infected thoracic
      endovascular aortic repairs (EVARs) [5/142:3.5%] and 3 endovascular aortic
      repairs (EVARs)[3/387:0.8%]. Median time from repair to presentation was 12
      months (range, 2-27 months). As the factors associated with infection,
      hemodialysis due to chronic kidney disease in 1, surgical treatment for the huge
      atheroma in 1, dental treatment in 2, treatment for infected aneurysm in 1,
      urinary tract infection after surgery for prostate in 1, aortoenteric fistula
      after TEVAR in 2 were considered. RESULTS: Five patients were treated with
      endograft explantation. The surgical mortality was 40% (2/5), during a follow-up,
      one more patient died with intracranial hemorrhage. The remaining 3 patients who
      were considered too high risk to remove the infectious endografts were treated
      conservatively with antibiotics. In 2 of them 1 died of respiratory failure, and
      multiple organ failure in 1. CONCLUSIONS: Infection of the endograft is a rare
      but devastating complication after endovascular repair of aortic aneurysms.
      Surgical removal of the infected prosthesis is accompanied with higher mortality,
      but antibiotics therapy cannot eradicate or cure the infection. In all cases, the
      factors associated with infection were calculated, and degenerative or infectious
      thrombi around the endovascular stent grafts were noted. Therefore, we consider
      that prophylactic antibiotic treatment may be necessary to prevent the bacteremia
      in the case of other surgical therapy or dental treatment.

PMID- 25595163
TI  - [Current surgical therapy for malignant pleural mesothelioma].
AB  - Malignant pleural mesothelioma (MPM) is a rare tumor and associated with very
      poor prognosis. The median survival time( MST) was 8.9 months for those treated
      by palliative care only. For a radical treatment, total removal of the tumor is
      the main therapy as well as other solid tumors, but these diffuse and infiltrate
      growth pattern of tumor make it difficult. The MST was 13 months for patients
      treated by surgery only. On the other hand, MST using pemetrexed/cisplatin was
      12.1 months. There are negative opinions for invasive surgical treatment such as
      extrapleural pneumonectomy (EPP). Currently surgical treatment of mesothelioma is
      conducted as part of the multidisciplinary treatment combined with chemotherapy
      and radiation therapy. 

PMID- 25595164
TI  - [Pulmonary dirofilariasis].
AB  - A 70-year-old man was admitted to our department for pulmonary nodule of 15 mm in
      diameter in the left lower lobe detected by chest computed tomography (CT). A
      possibility of malignant tumor could not be ruled out, and lung partial resection
      was performed. Pathological examination during operation revealed a coagulation
      necrosis and the lesion was finally diagnosed as pulmonary dirofilariasis. 

PMID- 25595165
TI  - Impact of Early Electronic Prescribing on Pharmacists' Clarification Calls in
      Four Community Pharmacies Located in St John's, Newfoundland.
AB  - BACKGROUND: Electronic prescribing (e-prescribing) can potentially help prevent
      medication errors. As the use of e-prescribing increases across Canada,
      understanding the benefits and gaps of early e-prescribing can help inform
      deployment of future e-prescribing systems. OBJECTIVE: The purpose of this
      exploratory study was to determine the prevalence of, reasons for, and average
      time taken for pharmacist clarification calls to prescribers for electronic
      medical record (EMR)-generated and handwritten prescriptions. METHODS: Four
      community pharmacies in St John's, Newfoundland, Canada prospectively collected
      information on clarification calls to prescribers for new prescriptions over a
      period of 17 to 19 weeks. Four semistructured interviews were conducted following
      the data collection period to gain further insight. RESULTS: An estimated 1.33%
      of handwritten prescriptions required clarification compared with 0.66% of EMR
      generated prescriptions. Overall, 1.11% of prescriptions required clarification
      with the prescriber. While illegibility was eliminated with EMR-generated
      prescriptions, clarification was still required for missing information (24%) and
      appropriateness (51%). Key themes, including errors unique to EMR-generated
      prescriptions, emerged from the qualitative interviews. CONCLUSIONS: Advanced e
      prescribing functionality will enable secure transmission of prescriptions from
      prescribers to a patient's pharmacy of choice through a provincial electronic
      Drug Information System (DIS)/Pharmacy Network, which will lessen the need for
      clarification calls, especially in the domains of missing information and
      appropriateness of the prescription. This exploratory study provides valuable
      insight into the benefits and gaps of early e-prescribing. Advanced e-prescribing
      systems will provide an opportunity for further realization of quality and safety
      benefits related to medication prescribing.

PMID- 25595166
TI  - Risk factors of carbapenem-resistant Klebsiella pneumoniae infection: a serious
      threat in ICUs.
AB  - BACKGROUND: Nosocomial infections caused by Carbapenem-resistant Klebsiella
      pneumoniae (CRKP) are increasing. Our aim in this study was to investigate the
      risk factors of CRKP infections. MATERIAL/METHODS: A retrospective cohort study
      was performed between 1 January and 31 December 2012 in ICU patients. Data was
      taken from the hospital infection control database for CRKP. The clinical samples
      collected from the patients were tested by an automatized system and disk
      diffusion. SPSS software v11.5 was used for statistical analysis. RESULTS:
      Totally, 105 Klebsiella pneumoniae isolates were found in 2012 and the carbapenem
      resistance rate was 48%. The first episode of infection was taken into risk
      factor analysis. Of the 98 patients, 61 (62.2%) were male and the mean and median
      ages were 30.4+/-29.8 and 25 (0-93). The length of stay was longer in the
      resistant group (p=0.026). Mortality was 48% in the whole group and similar
      between groups (p=0.533). There was a relationship between meropenem and third
      generation cephalosporin use and resistance (OR 3.244 (1.193-8.819) and OR: 3.590
      (1.056-12.209). The other risk factors in univariate analysis were:
      Immunosuppression OR: 2.186 (1.754-2.724), nasogastric catheter OR: 3.562 (1.317
      9.634), peripheral arterial catheter OR: 2.545 (1.027-6.307), and being admitted
      to the neurosurgical unit OR: 4.324 (1.110-16.842). CONCLUSIONS: Restriction of
      third-generation cephalosporin and carbapenem use and invasive procedures, along
      with infection control precautions and disinfection policies, may be effective in
      reducing the carbapenem resistance in ICUs.

PMID- 25595168
TI  - Stigma as a barrier to seeking health care among military personnel with mental
      health problems.
AB  - Approximately 60% of military personnel who experience mental health problems do
      not seek help, yet many of them could benefit from professional treatment. Across
      military studies, one of the most frequently reported barriers to help-seeking
      for mental health problems is concerns about stigma. It is, however, less clear
      how stigma influences mental health service utilization. This review will
      synthesize existing research on stigma, focusing on those in the military with
      mental health problems. We conducted a systematic review and meta-analysis of
      studies between 2001 and 2014 to examine the prevalence of stigma for seeking
      help for a mental health problem and its association with help-seeking
      intentions/mental health service utilization. Twenty papers met the search
      criteria. Weighted prevalence estimates for the 2 most endorsed stigma concerns
      were 44.2% (95% confidence interval: 37.1, 51.4) for "My unit leadership might
      treat me differently" and 42.9% (95% confidence interval: 36.8, 49.0) for "I
      would be seen as weak." Nine studies found no association between anticipated
      stigma and help-seeking intentions/mental health service use and 4 studies found
      a positive association. One study found a negative association between self
      stigma and intentions to seek help. Counterintuitively, those that endorsed high
      anticipated stigma still utilized mental health services or were interested in
      seeking help. We propose that these findings may be related to intention-behavior
      gaps or methodological issues in the measurement of stigma. Positive associations
      may be influenced by modified labeling theory. Additionally, other factors such
      as self-stigma and negative attitudes toward mental health care may be worth
      further attention in future investigation. 

PMID- 25595167
TI  - An integrated web-based mental health intervention of assessment-referral-care to
      reduce stress, anxiety, and depression in hospitalized pregnant women with
      medically high-risk pregnancies: a feasibility study protocol of hospital-based
      implementation.
AB  - BACKGROUND: At prevalence rates of up to 40%, rates of depression and anxiety
      among women with medically complex pregnancies are 3 times greater than those in
      community-based samples of pregnant women. However, mental health care is not a
      component of routine hospital-based antenatal care for medically high-risk
      pregnant women. OBJECTIVE: The purpose of this study is to evaluate the
      effectiveness and feasibility of the hospital-based implementation of a Web-based
      integrated mental health intervention comprising psychosocial assessment,
      referral, and cognitive behavioral therapy (CBT) for antenatal inpatients.
      METHODS: This study is a quasi-experimental design. Pregnant women are eligible
      to participate if they are (1) <37 weeks gestation, (2) admitted to the antenatal
      inpatient unit for >72 hours, (3) able to speak and read English or be willing to
      use a translation service to assist with completion of the questionnaires and
      intervention, (4) able to complete follow-up email questionnaires, (5) >16 years
      of age, and (6) not actively suicidal. Women admitted to the unit for induction
      (eg, <72-hour length of stay) are excluded. A minimum sample of 54 women will be
      recruited from the antenatal high-risk unit of a large, urban tertiary care
      hospital. All women will complete a Web-based psychosocial assessment and 6 Web
      based CBT modules. Results of the psychosocial assessment will be used by a Web
      based clinical decision support system to generate a clinical risk score and
      clinician prompts to provide recommendations for the best treatment and referral
      options. The primary outcome is self-reported prenatal depression, anxiety, and
      stress symptoms at 6-8 weeks postrecruitment. Secondary outcomes are postpartum
      depression, anxiety, and stress symptoms; self-efficacy; mastery; self-esteem;
      sleep; relationship quality; coping; resilience; Apgar score; gestational age;
      birth weight; maternal-infant attachment; infant behavior and development;
      parenting stress/competence at 3-months postpartum; and intervention cost
      effectiveness, efficiency, feasibility, and acceptability. All women will
      complete email questionnaires at 6-8 weeks postrecruitment and 3-months
      postpartum. Qualitative interviews with 10-15 health care providers and 15-30
      women will provide data on feasibility and acceptability of the intervention.
      RESULTS: The study was funded in September, 2014 and ethics was approved in
      November, 2014. Subject recruitment will begin January, 2015 and results are
      expected in December, 2015. Results of this study will determine (1) the
      effectiveness of an integrated Web-based prenatal mental health intervention on
      maternal and infant outcomes and (2) the feasibility of implementation of the
      intervention on a high-risk antenatal unit. CONCLUSIONS: This study will provide
      evidence and guidance regarding the implementation of a Web-based mental health
      program into routine hospital-based care for women with medically high-risk
      pregnancies.

PMID- 25595169
TI  - Post-traumatic stress disorder, physical activity, and eating behaviors.
AB  - Post-traumatic stress disorder (PTSD), a prevalent and costly psychiatric
      disorder, is associated with high rates of obesity and cardiometabolic diseases.
      Many studies have examined PTSD and risky behaviors (e.g., smoking,
      alcohol/substance abuse); far fewer have examined the relationship between PTSD
      and health-promoting behaviors. Physical activity and eating behaviors are 2
      lifestyle factors that impact cardiometabolic risk and long-term health. This
      comprehensive review of the literature (1980-2014) examined studies that reported
      physical activity and eating behaviors in adults with PTSD or PTSD symptoms. A
      systematic search of electronic databases identified 15 articles on PTSD-physical
      activity and 10 articles on PTSD-eating behaviors in adults. These studies
      suggest that there may be a negative association among PTSD, physical activity,
      and eating behaviors. Preliminary evidence from 3 pilot intervention studies
      suggests that changes in physical activity or diet may have beneficial effects on
      PTSD symptoms. There was considerable heterogeneity in the study designs and
      sample populations, and many of the studies had methodological and reporting
      limitations. More evidence in representative samples, using multivariable
      analytical techniques, is needed to identify a definitive relationship between
      PTSD and these health behaviors. Intervention studies for PTSD that examine
      secondary effects on physical activity/eating behaviors, as well as interventions
      to change physical activity/eating behaviors that examine change in PTSD, are
      also of interest. 

PMID- 25595170
TI  - Associations between cigarette smoking and pain among veterans.
AB  - Individuals with chronic pain often report using cigarettes to cope, and smoking
      and chronic pain appear prevalent among US veterans. Pain may be a barrier to
      cigarette cessation and abstinence in this population. Because of physiological
      effects, smoking cigarettes may also interfere with pain management. A better
      understanding of how cigarette use relates to pain may assist in veteran
      cigarette cessation and pain management efforts. To assist these efforts, we
      searched the literature using keywords, such as "pain," "smoking," and "veteran,"
      to identify 23 journal articles published from 1993 to 2013 that reported on
      studies examining pain and smoking variables among military or veteran
      populations. Studies found that veterans reported using cigarettes to cope with
      pain, there was greater occurrence of pain and disability among smokers in the
      military, and smoking increased the odds of veterans receiving an opioid
      prescription for pain and misusing opioids. Studies also found increased odds of
      pain and smoking among Veterans Health Administration patients with post
      traumatic stress disorder when compared with those without post-traumatic stress
      disorder. Studies support an interaction between pain and smoking among veterans.
      However, the mechanisms underlying this relationship remain unclear. Future
      studies focused on this interaction would benefit veteran populations. 

PMID- 25595171
TI  - Risk factors for homelessness among US veterans.
AB  - Homelessness among US veterans has been a focus of research for over 3 decades.
      Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines, this is the first systematic review to summarize research on
      risk factors for homelessness among US veterans and to evaluate the evidence for
      these risk factors. Thirty-one studies published from 1987 to 2014 were divided
      into 3 categories: more rigorous studies, less rigorous studies, and studies
      comparing homeless veterans with homeless nonveterans. The strongest and most
      consistent risk factors were substance use disorders and mental illness, followed
      by low income and other income-related factors. There was some evidence that
      social isolation, adverse childhood experiences, and past incarceration were also
      important risk factors. Veterans, especially those who served since the advent of
      the all-volunteer force, were at greater risk for homelessness than other adults.
      Homeless veterans were generally older, better educated, and more likely to be
      male, married/have been married, and to have health insurance coverage than other
      homeless adults. More studies simultaneously addressing premilitary, military,
      and postmilitary risk factors for veteran homelessness are needed. This review
      identifies substance use disorders, mental illness, and low income as targets for
      policies and programs in efforts to end homelessness among veterans. 

PMID- 25595172
TI  - Mental health among reserve component military service members and veterans.
AB  - Since 2001, the US military has increasingly relied on National Guard and reserve
      component forces to meet operational demands. Differences in preparation and
      military engagement experiences between active component and reserve component
      forces have long suggested that the psychiatric consequences of military
      engagement differ by component. We conducted a systematic review of prevalence
      and new onset of psychiatric disorders among reserve component forces and a meta
      analysis of prevalence estimates comparing reserve component and active component
      forces, and we documented stage-sequential drivers of psychiatric burden among
      reserve component forces. We identified 27 reports from 19 unique samples
      published between 1985 and 2012: 9 studies reporting on the reserve component
      alone and 10 reporting on both the reserve component and the active component.
      The pooled prevalence for alcohol use disorders of 14.5% (95% confidence
      interval: 12.7, 15.2) among the reserve component was higher than that of 11.7%
      (95% confidence interval: 10.9, 12.6) among the active component, while there
      were no component differences for depression or post-traumatic stress disorder.
      We observed substantial heterogeneity in prevalence estimates reported by the
      reserve component. Published studies suggest that stage-sequential risk factors
      throughout the deployment cycle predicted alcohol use disorders, post-traumatic
      stress disorder and, to a lesser degree, depression. Improved and more
      standardized documentation of the mental health burden, as well as study of
      explanatory factors within a life-course framework, is necessary to inform
      mitigating strategies and to reduce psychiatric burden among reserve component
      forces. 

PMID- 25595173
TI  - Prognostic factors for conjunctival melanoma: a study in ethnic Chinese patients.
AB  - BACKGROUND/OBJECTIVE: In patients with conjunctival melanomas, surgery is the
      first choice of treatment, but no standard adjuvant therapy has been established.
      In this study, we evaluated prognostic factors for conjunctival melanoma in
      ethnic Chinese patients. METHODS: Demographic data, known (published) prognostic
      factors, BRAF and KIT gene mutations, treatment strategies and outcomes were
      reviewed in 53 patients with pathologically confirmed conjunctival melanomas.
      Univariate and multivariate analyses of factors associated with survival were
      performed by the Kaplan-Meier method and a Cox proportional hazard model,
      respectively. RESULTS: Univariate analyses for 50 patients in whom data were
      available showed that a higher T stage (p=0.041), greater tumour thickness
      (p=0.006), local resection (p=0.033) and no adjuvant therapy (p=0.006) were
      associated with a worse recurrence-free survival (RFS) and metastasis-free
      survival (MFS). Patients with more involved quadrants also had worse MFS
      (p=0.039), while a higher T stage (p<0.001), local resection (p=0.008), and no
      adjuvant therapy (p=0.028) were associated with worse overall survival (OS).
      However, BRAF or KIT mutations showed no correlations with RFS, MFS or OS.
      Patients who received high-dose interferon (HDI) adjuvant therapy had a better
      RFS (p=0.004), MFS (p=0.001) and OS (p=0.005) than those who did not.
      Multivariate analysis showed that adjuvant therapy and tumour thickness were
      significant predictive factors for RFS, and the T stage was a significant
      predictive factor for OS. CONCLUSIONS: Adjuvant therapy and tumour thickness are
      significantly associated with RFS and T stage is a significant predictor of OS in
      Chinese patients with conjunctival melanomas. Patients may benefit from adjuvant
      therapy with HDI.

PMID- 25595174
TI  - Specific association of IL17A genetic variants with panuveitis.
AB  - BACKGROUND/AIMS: A pathogenic role of Th17 cells in uveitis has become clear in
      recent years. Therefore, in the present study, we aimed to evaluate the possible
      influence of the IL17A locus on susceptibility to non-anterior uveitis and its
      main clinical subgroups. METHODS: Five IL17A polymorphisms (rs4711998, rs8193036,
      rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using
      TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851
      ethnically matched controls. RESULTS: The case/control analysis yielded a
      consistent association between two of the analysed genetic variants, rs8193036
      and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E
      03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97,
      respectively). Subsequently, a specific association of both polymorphisms with
      the diffuse form of the disease was evident in the subphenotype analysis when
      considering this same genetic model (panuveitis vs posterior and intermediate
      uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of
      rs8193036 and rs2275913 were observed by conditional regression analysis.
      CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with
      panuveitis. Our data agree with the elevated levels of this cytokine that are
      found in patients with uveitis, supporting a crucial role of Th17 cells in this
      pathology. SUBTITLE: Our results clearly evidenced the role of IL17A as a novel
      genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells
      in the extensive inflammation of the uveal tract that occurs in this subtype of
      uveitis.

PMID- 25595175
TI  - Blepharoptosis surgery in patients with myasthenia gravis.
AB  - BACKGROUND/AIMS: To review our approach of cautious surgical correction of
      blepharoptosis in patients with myasthenia gravis (MG) to minimise risk of
      exposure complications. METHODS: Retrospective case note review of 30 patients
      with symptomatic eyelid concerns despite appropriate medical treatment, who
      underwent eyelid surgery. The mean age at diagnosis was 47 years. 13/30 patients
      had systemic MG, 14/30 ocular MG and 3/30 congenital MG. The main outcome
      measures were improvement in eyelid height and/or position, duration of a
      successful postoperative result, need for further surgical intervention, and
      intraoperative or postoperative complications. RESULTS: 38 blepharoptosis
      procedures were performed on 23 patients. Mean age at time of surgery was 62
      years, with an average follow-up of 29 months. 10 patients (16 eyelids) underwent
      anterior approach levator advancement, 4 patients (5 eyelids) posterior approach
      surgery and 8 patients (15 eyelids) brow suspension. One patient (2 eyelids) had
      tarsal switch surgery. An average improvement in eyelid height of 1.9 mm was
      achieved. Postoperative symptoms or signs of exposure keratopathy occurred in 17%
      of patients. This necessitated lid lowering in one eyelid of one patient. During
      follow-up, 37% of eyelids required further surgical intervention to improve the
      upper eyelid height, after an average of 19 months (range 0.5-49 months).
      CONCLUSIONS: Over a third of patients in our series required repeat surgery,
      which would be expected when the initial aim was to under-correct this group. In
      contrast to previous commentaries, the amount of eyelid excursion was not the
      main factor used to guide the surgical approach.

PMID- 25595177
TI  - A prospective pilot study of intravitreal aflibercept for the treatment of
      chronic central serous chorioretinopathy: the CONTAIN study.
AB  - AIM: To evaluate the role of intravitreal aflibercept injection as a treatment
      for eyes with chronic central serous chorioretinopathy (CSCR). METHODS: This
      prospective pilot study enrolled 12 patients with chronic CSCR who received a 6
      month treatment regimen of intravitreal aflibercept. Patients were followed with
      monthly Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected
      visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT)
      with enhanced depth imaging. RESULTS: All patients were men between 29 and 64
      years (median 55). Subfoveal fluid was present on OCT for a median duration of 6
      months (range 4-29 months) prior to treatment. Baseline BCVA ranged from 20/25 to
      20/160 (median 20/50) with a mean of 62 (SD=13) ETDRS letters. No patients
      experienced serious ocular or systemic adverse events over the course of the
      study. Post-treatment BCVA ranged from 20/20 to 20/200 (median 20/40), with a
      mean of 64 (SD=16) ETDRS letters (p=0.56). At baseline, three patients (25%) had
      BCVA of >=20/40 versus seven patients (58%) at the conclusion of the study. Two
      patients gained at least 15 ETDRS letters and no patients lost more than 15 ETDRS
      letters. Six of 12 patients (50%) had complete resolution of subfoveal fluid.
      Mean central macular thickness decreased from 400 um (SD=104 um) to 306 um (SD=94
      um) (p=0.03), and mean subfoveal fluid decreased from 159 um (SD=93 um) to 49 um
      (SD=68 um) (p=0.02). Mean choroidal thickness decreased from 307 um (SD=72 um) to
      263 um (SD=63 um) (p=0.0003). CONCLUSIONS: Intravitreal aflibercept was well
      tolerated over a 6-month treatment course for chronic CSCR. No change was
      observed in visual acuity metrics. Anatomic trends may suggest some morphological
      activity, but larger controlled trials are needed. TRIAL REGISTRATION NUMBER:
      NCT01710332.

PMID- 25595176
TI  - Spectral domain optical coherence tomography in patients with sickle cell
      disease.
AB  - AIM: To evaluate spectral domain optical coherence tomography (SD-OCT) changes in
      central retina and choroid in patients with sickle cell disease (SCD). METHODS:
      Data on visual acuity, severity of sickle cell retinopathy, macular volume scans
      and choroidal thickness on SD-OCT were analysed from 208 eyes of 107 consecutive
      patients referred for screening for SCD. The retinal and choroidal thickness of
      eyes with SCD were also compared with age and ethnicity matched controls.
      RESULTS: 44% of the eyes of patients with SCD showed discrete areas of retinal
      thinning in the temporal macular area. Proliferative sickle cell retinopathy was
      more prevalent in these eyes compared with SCD eyes with normal macular
      morphology (67% vs. 48%; p=0.0017). The temporal total and inner retinal
      thickness, macular volume and choroidal thickness were significantly lower in
      patients with SCD compared with age, gender and ethnicity matched controls.
      Macular splaying (widening of the macular contour) was noted in 30% of eyes in
      both groups. The choroidal and retinal thickness values showed good intergrader
      reliability using weighted kappa statistics (0.550-0.9). CONCLUSIONS:
      Quantitative and qualitative changes on SD-OCT are present in asymptomatic SCD
      eyes. Proliferative retinopathy is more prevalent in eyes with discrete areas of
      macular thinning.

PMID- 25595178
TI  - Sebaceous adenomas of the eyelid and Muir-Torre Syndrome.
AB  - BACKGROUND/AIMS: Sebaceous adenomas (SAs) are rare, benign sebaceous gland
      tumours of the eyelid. SAs may be associated with primary internal malignancies.
      This association is known as Muir-Torre Syndrome (MTS). The purpose of this study
      was to approximate the prevalence of SAs, to determine the reliability of the
      clinical diagnosis of SAs and to demonstrate immunohistochemical staining of DNA
      mismatch repair proteins mutL homologue 1 (MLH1) and mutS homologue 2 (MSH2) for
      a case of MTS. METHODS: We reviewed the histopathology reports from all eyelid
      specimens collected between 1993 and 2013 at the Henry C Witelson Ocular
      Pathology Laboratory to determine the proportion of SAs. For the SAs identified
      on histopathology, we looked at patient charts to see what diagnosis was
      originally suspected on clinical examination. Immunohistochemical staining for
      MLH1 and MSH2 was performed on all SAs to screen for MTS. RESULTS: Of the 5884
      eyelid specimens collected, 9 were SAs (6 women, 3 men; 42-72 years old). The
      diagnosis of SA was suspected clinically in only one of the nine cases based on
      the gross appearance of the eyelid lesion. Immunohistochemistry revealed one SA
      case with positive MLH1 expression and negative MSH2 expression. These findings
      prompted systemic work-up and this patient was diagnosed with MTS after discovery
      of a colon adenocarcinoma T2M0N0. CONCLUSIONS: The diagnosis of eyelid SA is
      rare. The importance of this benign eyelid tumour stems from its association with
      internal malignancies in MTS. Immunohistochemical staining of mismatch repair
      proteins MLH1 and MSH2 is a valid and accessible strategy for investigating MTS
      in patients with SAs.

PMID- 25595180
TI  - Dendritic Target Region-Specific Formation of Synapses Between Excitatory Layer 4
      Neurons and Layer 6 Pyramidal Cells.
AB  - Excitatory connections between neocortical layer 4 (L4) and L6 are part of the
      corticothalamic feedback microcircuitry. Here we studied the intracortical
      element of this feedback loop, the L4 spiny neuron-to-L6 pyramidal cell
      connection. We found that the distribution of synapses onto both putative
      corticothalamic (CT) and corticocortical (CC) L6 pyramidal cells (PCs) depends on
      the presynaptic L4 neuron type but is independent of the postsynaptic L6 PC type.
      L4 spiny stellate cells establish synapses on distal apical tuft dendrites of L6
      PCs and elicit slow unitary excitatory postsynaptic potentials (uEPSPs) in L6
      somata. In contrast, the majority of L4 star pyramidal neurons target basal and
      proximal apical oblique dendrites of L6 PCs and show fast uEPSPs. Compartmental
      modeling suggests that the slow uEPSP time course is primarily the result of
      dendritic filtering. This suggests that the dendritic target specificity of the 2
      L4 spiny neuron types is due to their different axonal projection patterns across
      cortical layers. The preferential dendritic targeting by different L4 neuron
      types may facilitate the generation of dendritic Ca(2+) or Na(+) action
      potentials in L6 PCs; this could play a role in synaptic gain modulation in the
      corticothalamic pathway. 

PMID- 25595179
TI  - The Representation of Object-Directed Action and Function Knowledge in the Human
      Brain.
AB  - The appropriate use of everyday objects requires the integration of action and
      function knowledge. Previous research suggests that action knowledge is
      represented in frontoparietal areas while function knowledge is represented in
      temporal lobe regions. Here we used multivoxel pattern analysis to investigate
      the representation of object-directed action and function knowledge while
      participants executed pantomimes of familiar tool actions. A novel approach for
      decoding object knowledge was used in which classifiers were trained on one pair
      of objects and then tested on a distinct pair; this permitted a measurement of
      classification accuracy over and above object-specific information. Region of
      interest (ROI) analyses showed that object-directed actions could be decoded in
      tool-preferring regions of both parietal and temporal cortex, while no
      independently defined tool-preferring ROI showed successful decoding of object
      function. However, a whole-brain searchlight analysis revealed that while
      frontoparietal motor and peri-motor regions are engaged in the representation of
      object-directed actions, medial temporal lobe areas in the left hemisphere are
      involved in the representation of function knowledge. These results indicate that
      both action and function knowledge are represented in a topographically coherent
      manner that is amenable to study with multivariate approaches, and that the left
      medial temporal cortex represents knowledge of object function. 

PMID- 25595182
TI  - Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure
      Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal
      Responsiveness.
AB  - The RNase Dicer is essential for the maturation of most microRNAs, a molecular
      system that plays an essential role in fine-tuning gene expression. To gain
      molecular insight into the role of Dicer and the microRNA system in brain
      function, we conducted 2 complementary RNA-seq screens in the hippocampus of
      inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs
      primarily affected by Dicer loss and their targets, respectively. Functional
      genomics analyses predicted the main biological processes and phenotypes
      associated with impaired microRNA maturation, including categories related to
      microRNA biology, signal transduction, seizures, and synaptic transmission and
      plasticity. Consistent with these predictions, we found that, soon after
      recombination, Dicer-deficient mice exhibited an exaggerated seizure response,
      enhanced induction of immediate early genes in response to different stimuli,
      stronger and more stable fear memory, hyperphagia, and increased excitability of
      CA1 pyramidal neurons. In the long term, we also observed slow and progressive
      excitotoxic neurodegeneration. Overall, our results indicate that interfering
      with microRNA biogenesis causes an increase in neuronal responsiveness and
      disrupts homeostatic mechanisms that protect the neuron against overactivation,
      which may explain both the initial and late phenotypes associated with the loss
      of Dicer in excitatory neurons. 

PMID- 25595181
TI  - Superficial Layer-Specific Histaminergic Modulation of Medial Entorhinal Cortex
      Required for Spatial Learning.
AB  - The medial entorhinal cortex (MEC) plays a crucial role in spatial learning and
      memory. Whereas the MEC receives a dense histaminergic innervation from the
      tuberomamillary nucleus of the hypothalamus, the functions of histamine in this
      brain region remain unclear. Here, we show that histamine acts via H1Rs to
      directly depolarize the principal neurons in the superficial, but not deep,
      layers of the MEC when recording at somata. Moreover, histamine decreases the
      spontaneous GABA, but not glutamate, release onto principal neurons in the
      superficial layers by acting at presynaptic H3Rs without effect on synaptic
      release in the deep layers. Histamine-induced depolarization is mediated via
      inhibition of Kir channels and requires the activation of protein kinase C,
      whereas the inhibition of spontaneous GABA release by histamine depends on
      voltage-gated Ca(2+) channels and extracellular Ca(2+). Furthermore,
      microinjection of the H1R or H3R, but not H2R, antagonist respectively into the
      superficial, but not deep, layers of MEC impairs rat spatial learning as assessed
      by water maze tasks but does not affect the motor function and exploratory
      activity in an open field. Together, our study indicates that histamine plays an
      essential role in spatial learning by selectively regulating neuronal
      excitability and synaptic transmission in the superficial layers of the MEC. 

PMID- 25595183
TI  - Functional Imaging of the Developing Brain at the Bedside Using Diffuse Optical
      Tomography.
AB  - While histological studies and conventional magnetic resonance imaging (MRI)
      investigations have elucidated the trajectory of structural changes in the
      developing brain, less is known regarding early functional cerebral development.
      Recent investigations have demonstrated that resting-state functional
      connectivity MRI (fcMRI) can identify networks of functional cerebral connections
      in infants. However, technical and logistical challenges frequently limit the
      ability to perform MRI scans early or repeatedly in neonates, particularly in
      those at greatest risk for adverse neurodevelopmental outcomes. High-density
      diffuse optical tomography (HD-DOT), a portable imaging modality, potentially
      enables early continuous and quantitative monitoring of brain function in
      infants. We introduce an HD-DOT imaging system that combines advancements in cap
      design, ergonomics, and data analysis methods to allow bedside mapping of
      functional brain development in infants. In a cohort of healthy, full-term
      neonates scanned within the first days of life, HD-DOT results demonstrate strong
      congruence with those obtained using co-registered, subject-matched fcMRI and
      reflect patterns of typical brain development. These findings represent a
      transformative advance in functional neuroimaging in infants, and introduce HD
      DOT as a powerful and practical method for quantitative mapping of early
      functional brain development in normal and high-risk neonates. 

PMID- 25595184
TI  - Cytoarchitecture-Dependent Decrease in Propagation Velocity of Cortical Spreading
      Depression in the Rat Insular Cortex Revealed by Optical Imaging.
AB  - Cortical spreading depression (SD) is a self-propagating wave of depolarization
      accompanied by a substantial disturbance of the ionic distribution between the
      intra- and extracellular compartments. Glial cells, including astrocytes, play
      critical roles in maintenance of the extracellular environment, including ionic
      distribution. Therefore, SD propagation in the cerebral cortex may depend on the
      density of astrocytes. The present study aimed to examine the profile of SD
      propagation in the insular cortex (IC), which is located between the neocortex
      and paleocortex and is where the density of astrocytes gradually changes. The
      velocity of SD propagation in the neocortex, including the somatosensory, motor,
      and granular insular cortices (5.7 mm/min), was higher than that (2.8 mm/min) in
      the paleocortex (agranular insular and piriform cortices). Around thick vessels,
      including the middle cerebral artery, SD propagation was frequently delayed and
      sometimes disappeared. Immunohistological analysis of glial fibrillary acidic
      protein (GFAP) demonstrated the sparse distribution of astrocytes in the
      somatosensory cortex and the IC dorsal to the rhinal fissure, whereas the ventral
      IC showed a higher density of astrocytes. These results suggest that cortical
      cytoarchitectonic features, which possibly involve the distribution of
      astrocytes, are crucial for regulating the velocity of SD propagation in the
      cerebral cortex. 

PMID- 25595186
TI  - WWOX, the chromosomal fragile site FRA16D spanning gene: its role in metabolism
      and contribution to cancer.
AB  - The WWOX gene spans the common chromosomal fragile site FRA16D that is located
      within a massive (780 kb) intron. The WWOX gene is very long, at 1.1 Mb, which
      may contribute to the very low abundance of the full-length 1.4 kb mRNA.
      Alternative splicing also accounts for a variety of aberrant transcripts, most of
      which are devoid of C-terminal sequences required for WWOX to act as an
      oxidoreductase. The mouse WWOX gene also spans a chromosomal fragile site
      implying some sort of functional relationship that confers a selective advantage.
      The encoded protein domains of WWOX are conserved through evolution (between
      humans and Drosophila melanogaster) and include WW domains, an NAD -binding site,
      short-chain dehydrogenase/reductase enzyme and nuclear compartmentalization
      signals. This homology has enabled functional analyses in D. melanogaster that
      demonstrate roles for WWOX in reactive oxygen species regulation and metabolism.
      Indeed the human WWOX gene is also responsive to altered metabolism. Cancer cells
      typically exhibit altered metabolism (Warburg effect). Many cancers exhibit
      FRA16D DNA instability that results in aberrant WWOX expression and is associated
      with poor prognosis for these cancers. It is therefore thought that aberrant WWOX
      expression contributes to the altered metabolism in cancer. In addition, others
      have found that a specific (low-expression) allele of WWOX genotype contributes
      to cancer predisposition.

PMID- 25595185
TI  - WWOX, large common fragile site genes, and cancer.
AB  - WWOX is a gene that spans an extremely large chromosomal region. It is derived
      from within chromosomal band 16q23.2 which is a region with frequent deletions
      and other alterations in a variety of different cancers. This chromosomal band
      also contains the FRA16D common fragile site (CFS). CFSs are chromosomal regions
      found in all individuals which are highly unstable. WWOX has also been
      demonstrated to function as a tumor suppressor that is involved in the
      development of many cancers. Two other highly unstable CFSs, FRA3B (3p14.2) and
      FRA6E (6q26), also span extremely large genes, FHIT and PARK2, respectively, and
      these two genes are also found to be important tumor suppressors. There are a
      number of interesting similarities between these three large CFS genes. In spite
      of the fact that they are derived from some of the most unstable chromosomal
      regions in the genome, they are found to be highly evolutionarily conserved and
      the chromosomal region spanning the mouse homologs of both WWOX and FHIT are also
      CFSs in mice. Many of the other CFSs also span extremely large genes and many of
      these are very attractive tumor suppressor candidates. WWOX is therefore a member
      of a very interesting family of very large CFS genes.

PMID- 25595187
TI  - Modulation of Sonic hedgehog signaling and WW domain containing oxidoreductase
      WOX1 expression enhances radiosensitivity of human glioblastoma cells.
AB  - WW domain containing oxidoreductase, designated WWOX, FOR or WOX1, is a known pro
      apoptotic factor when ectopically expressed in various types of cancer cells,
      including glioblastoma multiforme (GBM). The activation of sonic hedgehog (Shh)
      signaling, especially paracrine Shh secretion in response to radiation, is
      associated with impairing the effective irradiation of cancer cells. Here, we
      examined the role of Shh signaling and WOX1 overexpression in the
      radiosensitivity of human GBM cells. Our results showed that ionizing irradiation
      (IR) increased the cytoplasmic Shh and nuclear Gli-1 content in GBM U373MG and
      U87MG cells. GBM cells with exogenous Shh treatment exhibited similar results.
      Pretreatment with Shh peptides protected U373MG and U87MG cells against IR in a
      dose-dependent manner. Cyclopamine, a Hedgehog/Smoothened (SMO) inhibitor,
      reversed the protective effect of Shh in U87MG cells. Cyclopamine increased Shh
      plus IR-induced H2AX, a marker of DNA double-strand breaks, in these cells. To
      verify the role of Shh signaling in the radiosensitivity of GBM cells, we tested
      the effect of the Gli family zinc finger 1 (Gli-1) inhibitor zerumbone and found
      that it could sensitize GBM cells to IR. We next examined the role of WOX1 in
      radiosensitivity. Overexpression of WOX1 enhanced the radiosensitivity of U87MG
      (possessing wild type p53 or WTp53) but not U373MG (harboring mutant p53 or
      MTp53) cells. Pretreatment with Shh peptides protected both WOX1-overexpressed
      U373MG and U87MG cells against IR and increased the cytoplasmic Shh and nuclear
      Gli-1 content. Zerumbone enhanced the radiosensitivity of WOX1-overexpressed
      U373MG and U87MG cells. In conclusion, overexpression of WOX1 preferentially
      sensitized human GBM cells possessing wild type p53 to radiation therapy.
      Blocking of Shh signaling may enhance radiosensitivity independently of the
      expression of p53 and WOX1. The crosstalk between Shh signaling and WOX1
      expression in human glioblastoma warrants further investigation.

PMID- 25595188
TI  - Perspectives of induced pluripotent stem cells for cardiovascular system
      regeneration.
AB  - Induced pluripotent stem cells (iPSCs) hold great promise for basic research and
      regenerative medicine. They offer the same advantages as embryonic stem cells
      (ESCs) and moreover new perspectives for personalized medicine. iPSCs can be
      generated from adult somatic tissues by over-expression of a few defined
      transcription factors, including Oct4, Sox2, Klf4, and c-myc. For regenerative
      medicine in particular, the technology provides great hope for patients with
      incurable diseases or potentially fatal disorders such as heart failure. The
      endogenous regenerative potentials of adult hearts are extremely limited and
      insufficient to compensate for myocardial loss occurring after myocardial
      infarction. Recent discoveries have demonstrated that iPSCs have the potential to
      significantly advance future cardiovascular regenerative therapies. Moreover,
      iPSCs can be generated from somatic cells of patients with genetic basis for
      their disease. This human iPSC derivates offer tremendous potential for new
      disease models. This paper reviews current applications of iPSCs in
      cardiovascular regenerative medicine and discusses progress in modeling
      cardiovascular diseases using iPSCs-derived cardiac cells. 

PMID- 25595189
TI  - Hemodynamics and right-ventricle functional characteristics of a swine carotid
      artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month
      experimental study.
AB  - The continuous changes in pulmonary hemodynamic properties and right ventricular
      (RV) function in pulmonary arterial hypertension (PAH) have not been fully
      characterized in large animal model of PAH induced by a carotid artery-jugular
      vein shunt. A minipig model of PAH was induced by a surgical anastomosis between
      the left common carotid artery and the left jugular vein. The model was validated
      by catheter examination and pathologic analyses, and the hemodynamic features and
      right-ventricle functional characteristics of the model were continuously
      observed by Doppler echocardiography. Of the 45 minipigs who received the
      surgery, 27 survived and were validated as models of PAH, reflected by mean
      pulmonary artery pressure >=25 mmHg, and typical pathologic changes of pulmonary
      arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary
      hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular
      ejection time) were temporarily increased, then reduced later, similar to changes
      in tricuspid annular displacement. The Tei index of the RV was elevated,
      indicating a progressive impairment in RV function. Surgical anastomosis between
      carotid artery and jugular vein in a minipig is effective to establish PAH, and
      non-invasive hemodynamic and right-ventricle functional indices measured by
      Doppler echocardiography may be used as early indicators of PAH. 

PMID- 25595190
TI  - Dexamethasone and rosiglitazone are sufficient and necessary for producing
      functional adipocytes from mesenchymal stem cells.
AB  - The final product of adipogenesis is a functional adipocyte. This mature cell
      acquires the necessary machinery for lipid metabolism, loses its proliferation
      potential, increases its insulin sensitivity, and secretes adipokines.
      Multipotent mesechymal stromal cells have been recognized as a source of
      adipocytes both in vivo and in vitro. The in vitro adipogenic differentiation of
      human MSC (hMSC) has been induced up to now by using a complex stimulus which
      includes dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin (a
      classical cocktail) and evaluated according to morphological changes. The present
      work was aimed at demonstrating that the simultaneous activation of
      dexamethasone's canonical signaling pathways, through the glucocorticoid receptor
      and CCAAT-enhancer-binding proteins (C/EBPs) and rosiglitazone through peroxisome
      proliferator-activated receptor gamma (PPAR-gamma) is sufficient yet necessary
      for inducing hMSC adipogenic differentiation. It was also ascertained that hMSC
      exposed just to dexamethasone and rosiglitazone (D&R) differentiated into cells
      which accumulated neutral lipid droplets, expressed C/EBP-alpha, PPAR-gamma, aP2,
      lipoprotein lipase, acyl-CoA synthetase, phosphoenolpyruvate carboxykinase,
      adiponectin, and leptin genes but did not proliferate. Glucose uptake was dose
      dependent on insulin stimulus and high levels of adipokines were secreted (i.e.
      displaying not only the morphology but also expressing mature adipocytes'
      specific genes and functional characteristics). This work has demonstrated that
      (i) the activating C/EBPs and PPAR-gamma signaling pathways were sufficient to
      induce adipogenic differentiation from hMSC, (ii) D&R producing functional
      adipocytes from hMSC, (iii) D&R induce adipogenic differentiation from mammalian
      MSC (including those which are refractory to classical adipogenic differentiation
      stimuli). D&R would thus seem to be a useful tool for MSC characterization,
      studying adipogenesis pathways and producing functional adipocytes.

PMID- 25595191
TI  - Regulation of cell signaling and apoptosis by tumor suppressor WWOX.
AB  - Human fragile WWOX gene encodes a tumor suppressor WW domain-containing
      oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX
      prevents apoptotic cell death induced by a variety of stress stimuli, such as
      tumor necrosis factor, UV radiation, and chemotherapeutic drug treatment. Loss of
      WWOX gene expression due to gene deletions, loss of heterozygosity, chromosomal
      translocations, or epigenetic silencing is frequently observed in human malignant
      cancer cells. Acquisition of chemoresistance in squamous cell carcinoma,
      osteosarcoma, and breast cancer cells is associated with WWOX deficiency. WWOX
      protein physically interacts with many signaling molecules and exerts its
      regulatory effects on gene transcription and protein stability and subcellular
      localization to control cell survival, proliferation, differentiation, autophagy,
      and metabolism. In this review, we provide an overview of the recent advances in
      understanding the molecular mechanisms by which WWOX regulates cellular functions
      and stress responses. A potential scenario is that activation of WWOX by
      anticancer drugs is needed to overcome chemoresistance and trigger cancer cell
      death, suggesting that WWOX can be regarded as a prognostic marker and a
      candidate molecule for targeted cancer therapies.

PMID- 25595192
TI  - A novel quantitative body shape score for detecting association between obesity
      and hypertension in China.
AB  - BACKGROUND: Obesity is a major independent risk factor for chronic diseases such
      as hypertension and coronary diseases, it might not be only related to the amount
      of body fat but its distribution. The single body mass index (BMI), waist
      circumference (WC), waist to hip ratio (WHR) or waist to stature ratio (WSR)
      provides limited information on fat distribution, and the debate about which one
      is the best remained. On the other hand, the current classification of body shape
      is qualitative rather than quantitative, and only crudely measure fat
      distribution. Therefore, a synthetical index is highly desirable to quantify body
      shape. METHODS: Based on the China Health and Nutrition Survey (CHNS) data, using
      Lohmaller PLSPM algorithm, six Partial Least Squares Path Models (PLSPMs) between
      the different obesity measurements and hypertension as well as two synthetical
      body shape scores (BSS1 by BMI/WC/Hip circumference, BSS2 by BMI/WC/WHR/WSR) were
      created. Simulation and real data analysis were conducted to assess their
      performance. RESULTS: Statistical simulation showed the proposed model was stable
      and powerful. Totally 15,172 (6,939 male and 8,233 female) participants aged from
      18 to 87 years old were included. It indicated that age, height, weight, WC, WHR,
      WSR, SBP, DBP, the prevalence of hypertension and obesity were significantly sex
      different. BMI, WC, WHR, WSR, Hip, BSS1 and BSS2 between hypertension and
      normotensive group are significantly different (p < 0.05). PLSPM method
      illustrated the biggest path coefficients (95% confidence interval, CI) were
      0.220(0.196, 0.244) for male and 0.205(0.182, 0.228) for female in model of BSS1.
      The area under receiver-operating characteristic curve (AUC(95% CI)) of
      BSS1(0.839(0.831,0.847)) was significantly larger than that of
      BSS2(0.834(0.825,0.842)) as well as the four single indices for female, and
      similar trend can be found for male. CONCLUSIONS: BSS1 was an excellent
      measurement for quantifying body shape and detecting the association between body
      shape and hypertension.

PMID- 25595194
TI  - Acupuncture for chronic knee pain: a randomised clinical trial. Authors' reply.

PMID- 25595195
TI  - Randomised controlled trial on the use of acupuncture in adults with chronic, non
      responding anxiety symptoms.
AB  - BACKGROUND: A group of adults can be identified with chronic non-responding
      anxiety symptoms who have repeatedly accessed treatments through their GP, such
      as cognitive behaviour therapy, bibliotherapy and medication, but with no effect.
      These patients make heavy use of health service resources with no beneficial
      outcome. This study aims to test the effect of an acupuncture formula of three
      specific acupuncture points, suggested in a previous pilot study. METHOD: 40
      participants from a psychiatry waiting list were randomised into one of two
      groups: group 1 (n=25) received 10 weeks of acupuncture at PC6, HT7 and LR3, and
      group 2 was a waiting list control group. The waiting list group (n=15) then
      received acupuncture. Both groups were followed up for 10 weeks after treatment.
      The outcome measure was the State and Trait Anxiety Inventory. RESULTS: 36
      patients completed the study, with two dropouts in each group. State anxiety
      scores in the acupuncture group decreased from 57.7 (SD 13.1) to 38.8 (12.0);
      scores in the waiting list control group decreased from 61.5 (11.6) to 60.6
      (11.7). The difference was highly significant (p<0.0001). Similar changes were
      seen for trait anxiety scores. The control group showed similar statistically
      significant improvements when they received acupuncture. The improvements were
      maintained after 10 weeks of follow-up in each group. CONCLUSIONS: Acupuncture is
      a promising intervention for patients with chronic anxiety symptoms that have
      proven resistant to other forms of treatment.

PMID- 25595193
TI  - Decoding the processing of lying using functional connectivity MRI.
AB  - BACKGROUND: Previous functional MRI (fMRI) studies have demonstrated group
      differences in brain activity between deceptive and honest responses. The
      functional connectivity network related to lie-telling remains largely
      uncharacterized. METHODS: In this study, we designed a lie-telling experiment
      that emphasized strategy devising. Thirty-two subjects underwent fMRI while
      responding to questions in a truthful, inverse, or deceitful manner. For each
      subject, whole-brain functional connectivity networks were constructed from
      correlations among brain regions for the lie-telling and truth-telling
      conditions. Then, a multivariate pattern analysis approach was used to
      distinguish lie-telling from truth-telling based on the functional connectivity
      networks. RESULTS: The classification results demonstrated that lie-telling could
      be differentiated from truth-telling with an accuracy of 82.81% (85.94% for lie
      telling, 79.69% for truth-telling). The connectivities related to the fronto
      parietal networks, cerebellum and cingulo-opercular networks are most
      discriminating, implying crucial roles for these three networks in the processing
      of deception. CONCLUSIONS: The current study may shed new light on the neural
      pattern of deception from a functional integration viewpoint.

PMID- 25595196
TI  - Socio-economic factors related with the subjective well-being of the rural
      elderly people living independently in China.
AB  - BACKGROUND: Many Chinese elderly increasingly face the serious problem of the
      "empty nest" phenomenon. The elderly living independently, also called empty-nest
      elderly, refers to elderly people living alone whose children left home. However
      few studies concerned about the subjective well-being (SWB) of the elderly living
      independently. METHODS: This study employs The Memorial University of
      Newfoundland Scale of Happiness (MUNSH) to explore the SWB of the elderly living
      independently in rural areas of Wenzhou, a relatively developed region in China.
      536 sampled are randomly selected. RESULTS: The results indicate that
      participants obtained low scores in positive affect, positive experience, and the
      total SWB score, but high scores in negative affect and negative experience. Age,
      low education, poor health condition and little income were found to be
      negatively correlated with SWB. The SWB score of the elderly living with a spouse
      is higher than those who divorced or lost their spouse and the score of women is
      lower than that of men. In addition, the survey revealed that children's support
      has a positive influence on the SWB of the rural elderly living independently.
      CONCLUSIONS: The elderly living independently in rural Wenzhou, China have
      unfavorable SWB. Poor socio-economic statuses are negative impact factors. But
      the children's support can help to improve. Special attention is needed to those
      with lower socio-economic status and less children's support.

PMID- 25595197
TI  - High sensitivity C-reactive protein and cerebral white matter hyperintensities on
      magnetic resonance imaging in migraine patients.
AB  - BACKGROUND: Migraine is a common headache disorder that may be associated with
      vascular disease and cerebral white matter hyperintensities (WMHs) on magnetic
      resonance imaging (MRI) scan. High sensitivity C-reactive protein (hs-CRP) is a
      marker of inflammation that may predict subclinical atherosclerosis. However, the
      relation between migraine, vascular risks, and WMHs is unknown. We evaluated hs
      CRP levels and the relation between hs-CRP level and WMHs in adult migraine
      patients. METHODS: This case-control study included 432 subjects (216 migraine
      patients [without aura, 143 patients; with aura, 73 patients]; 216 healthy
      control subjects without migraine; age range 18-50 y). Migraine diagnosis was
      determined according to the International Classification of Headache Disorders II
      diagnostic criteria. The migraine patients and control subjects had no known
      vascular risk factors, inflammatory disease, or comorbid disease. The presence
      and number of WMHs on MRI scans were determined, and serum hs-CRP levels were
      measured by latex-enhanced immunoturbidimetry. RESULTS: Mean hs-CRP level was
      significantly greater in migraine patients (1.94 +/- 2.03 mg/L) than control
      subjects (0.82 +/- 0.58 mg/L; P <= .0001). The mean number of WMHs per subject
      and the presence of WMHs was significantly greater in migraine patients (69
      patients [31.9%]; 1.68 +/- 3.12 mg/dL) than control subjects (21 subjects [9.7%];
      0.3 +/- 1.3; P <= .001). However, there was no correlation between hs-CRP level
      and WMHs in migraine patients (r = 0.024; not significant). The presence of WMHs
      was increased 4.35-fold in migraine patients (odds ratio 4.35, P <= .001).
      CONCLUSIONS: High hs-CRP level may be a marker of the proinflammatory state in
      migraine patients. However, the absence of correlation between hs-CRP level and
      WMHs suggests that hs-CRP is not causally involved in the pathogenesis of WMHs in
      migraine patients. The WMHs were located mostly in the frontal lobe and
      subcortical area.

PMID- 25595198
TI  - Seroprevalence of Triatoma virus (Dicistroviridae: Cripaviridae) antibodies in
      Chagas disease patients.
AB  - BACKGROUND: Chagas disease is caused by Trypanosoma cruzi, and humans acquire the
      parasite by exposure to contaminated feces from hematophagous insect vectors
      known as triatomines. Triatoma virus (TrV) is the sole viral pathogen of
      triatomines, and is transmitted among insects through the fecal-oral route and,
      as it happens with T. cruzi, the infected insects release the virus when
      defecating during or after blood uptake. METHODS: In this work, we analysed the
      occurrence of anti-TrV antibodies in human sera from Chagas disease endemic and
      non-endemic countries, and developed a mathematical model to estimate the
      transmission probability of TrV from insects to man, which ranged between 0.00053
      and 0.0015. RESULTS: Our results confirm that people with Chagas disease living
      in Bolivia, Argentina and Mexico have been exposed to TrV, and that TrV is unable
      to replicate in human hosts. CONCLUSIONS: We presented the first experimental
      evidence of antibodies against TrV structural proteins in human sera.

PMID- 25595201
TI  - Determinants of underweight, stunting and wasting among schoolchildren.
AB  - BACKGROUND: The cause of under-nutrition in schoolchildren is complex and varying
      from region to region. However, identifying the cause is the basic step for
      nutritional intervention programs. METHODS: School based cross-sectional survey
      was conducted among 450 schoolchildren aged 7-14 years, using multi-stage
      sampling techniques in Dale Woreda, southern Ethiopia. A structured questionnaire
      and 24-hour recall methods were administered to determine the sociodemographic
      and dietary intake of participants. Stool microscopic examination was done.
      Weight and height were measured using a standard calibrated scale. Odds ratio
      generated from logistic regression was used to determine the strength of
      variables association. RESULTS: Older age group (10-14 vs. 7-9) (AOR = 3.4; 95%
      CI, 1.7-6.6) and having Trichuris Trichura infection (AOR = 3.9; 95% CI, 1.4 
      11.6) increased the risk of being stunted. Children whose mothers have completed
      primary education are less likely to be stunted than children whose mothers do
      not have formal education (AOR = 0.3; 95% CI, 0.2-0.8). Having large family size
      (AOR = 3.3; 95% CI, 1.4-7.9) and inadequate intake of carbohydrate (AOR = 3.1;
      95% CI, 1.4-6.8) were independent predictors of wasting. Children whose mothers
      completed primary education are less likely to be underweight (AOR = 0.3; 95% CI,
      0.1-0.9). Children live in food insecure households are more likely to be
      stunted, under-weight and wasted than children live in food secure households
      (AOR = 2.5; 95%, 1-5.6; AOR = 3.9; 95% CI, 1.2-12.0; AOR = 4.8; 95% CI, 1.7
      13.6;). CONCLUSION: Household food insecurity, low maternal education and
      infection with Trichuris trichura were some of the major factors contributing to
      under-nutrition in the study area.

PMID- 25595200
TI  - Effects of bovine leukemia virus infection on milk neutrophil function and the
      milk lymphocyte profile.
AB  - The effects of bovine leukemia virus (BLV) on the immune response have been
      extensively investigated; however, its effects on mammary gland immunity are only
      speculative. Although BLV has a tropism for B cells, it can affect both adaptive
      and innate immunities because these systems share many effector mechanisms. This
      scenario is the basis of this investigation of the effects of BLV on mammary
      gland immunity, which is largely dependent upon neutrophilic functions. Thus, the
      present study sought to examine neutrophilic functions and the lymphocyte profile
      in the milk of naturally BLV-infected cows. The viability of the milk neutrophils
      and the percentage of milk neutrophils that produced reactive oxygen species
      (ROS) or phagocytosed Staphylococcus aureus were similar between BLV-infected and
      BLV-uninfected dairy cows. Furthermore, the expression of CD62L and CD11b by the
      milk neutrophils and the percentage of milk neutrophils (CH138+ cells) that were
      obtained from the udder quarters of the BLV-infected cows were not altered.
      Conversely, the median fluorescence intensity (MFI) representing intracellular
      ROS production and the phagocytosis of S. aureus, the expression of CD44 by the
      milk neutrophils and the percentage of apoptotic B cells were lower in the milk
      cells from BLV-infected dairy cows, particularly those from animals with
      persistent lymphocytosis (PL). The lymphocyte subsets were not different among
      the groups, with the exception of the percentage of CD5-/CD11b- B cells, which
      was higher in the milk cells from BLV-infected cows, particularly those with PL.
      Thus, the present study provides novel insight into the implications of BLV
      infection for mammary gland immunity. 

PMID- 25595199
TI  - A case-control observational study of insulin resistance and metabolic syndrome
      among the four phenotypes of polycystic ovary syndrome based on Rotterdam
      criteria.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with an increased risk
      of insulin resistance (IR), metabolic syndrome (MetS), impaired glucose tolerance
      (IGT) and type 2 diabetes mellitus (T2DM). Metabolic aspects of the four PCOS
      phenotypes remain to be fully defined. The aim of this study was to compare
      metabolic parameters and insulin resistance among the four PCOS phenotypes
      defined according to the Rotterdam criteria and to determine predictors of these
      complications. METHODS: A total of 526 reproductive-aged women were included in
      this observational case-control study. Of these, 263 were diagnosed as a PCOS
      based on Rotterdam criteria and 263 infertile women with no evidence of PCOS were
      recruited as controls. Biochemical, metabolic and insulin resistance parameters
      were compared in the two groups and the frequency of MetS and IR were compared
      among the four phenotypes. Data were analyzed for statistical significance using
      Student's t-test and one way analysis of variance followed by a post-hoc test
      (least significant difference). Chi-square tests were used to compare
      proportions. Univariate and multivariate logistic regression analyses were also
      applied. RESULTS: IR was identified in 112 (42.6%) of the PCOS women and 45
      (17.1%) of the control (P <0.001). There were no significant differences in the
      frequency of IR and MetS between the four PCOS phenotypes. Homeostatic model
      assessment for IR (HOMA-IR) >=3.8 was the most common IR parameter in PCOS and
      control groups. Women with oligo-anovulation (O) and PCO morphology (P) had a
      significantly lower level of 2-h postprandial insulin compared to women with O, P
      and hyperandrogenism (H) phenotypes. Logistic regression analysis showed that
      body mass index, waist circumference, triglyceride/high-density lipoprotein ratio
      (cardiovascular risk), HOMA-IR and glucose abnormalities (T2DM) were associated
      with increased risk of having MetS (P < 0.05). CONCLUSIONS: PCOS women with (O +
      P) show milder endocrine and metabolic abnormalities. Although, there were no
      significant differences in IR, MetS and glucose intolerance between the four PCOS
      phenotypes, women with PCOS are at higher risk of impaired glucose tolerance and
      undiagnosed diabetes.

PMID- 25595202
TI  - A cross sectional survey on social, cultural and economic determinants of obesity
      in a low middle income setting.
AB  - INTRODUCTION: Obesity is an increasing problem in South Asian countries and Sri
      Lanka is no exception. The socioeconomic determinants of obesity in Sri Lanka,
      and in neighbouring countries are inadequately described. Aim was to describe
      social, cultural and economic determinants of obesity in a representative sample
      from Kalutara District in Sri Lanka. METHODS: This was a cross sectional
      descriptive study conducted among adults aged 35-64 years. A representative
      sample was selected using stratified random cluster sampling method from urban,
      rural and plantation sectors of Kalutara District. Data were collected using a
      pre-tested questionnaire. A body mass index of 23.01 kg/m(2)-27.50 kg/m(2) was
      considered as overweight and >=27.51 kg/m(2) as obese. Waist circumference (WC)
      of >= 90 cm and >=80 cm was regarded as high for men and women respectively.
      Significance of prevalence of obesity categories across different socio-economic
      strata was determined by chi square test for trend. RESULTS: Of 1234 adults who
      were screened, age and sex adjusted prevalence of overweight, obesity and
      abdominal obesity (high WC) were 33.2% (male 27.3%/female 38.7%), 14.3% (male
      9.2%/female 19.2%) and 33.6% (male 17.7%/female 49.0%) respectively. The Muslims
      had the highest prevalence of all three obesity categories. Sector, education,
      social status quintiles and area level deprivation categories show a non linear
      social gradient while income shows a linear social gradient in all obesity
      categories, mean BMI and mean WC. The differences observed for mean BMI and mean
      WC between the lowest and highest socioeconomic groups were statistically
      significant. CONCLUSION: There is a social gradient in all three obesity
      categories with higher prevalence observed in the more educated, urban, high
      income and high social status segments of society. The higher socioeconomic
      groups are still at a higher risk of all types of obesity despite other public
      health indicators such as maternal and infant mortality displaying an established
      social gradient.

PMID- 25595203
TI  - Leishmania enriettii: biochemical characterisation of lipophosphoglycans (LPGs)
      and glycoinositolphospholipids (GIPLs) and infectivity to Cavia porcellus.
AB  - BACKGROUND: Leishmania enriettii is a species non-infectious to man, whose
      reservoir is the guinea pig Cavia porcellus. Many aspects of the parasite-host
      interaction in this model are unknown, especially those involving parasite
      surface molecules. While lipophosphoglycans (LPGs) and glycoinositolphospholipids
      (GIPLs) of Leishmania species from the Old and New World have already been
      described, glycoconjugates of L. enriettii and their importance are still
      unknown. METHODS: Mice peritoneal macrophages from C57BL/6 and knock-out (TLR2 -/
      , TLR4 -/-) were primed with IFN-gamma and stimulated with purified LPG and GIPLs
      from both species. Nitric oxide and cytokine production were performed. MAPKs
      (p38 and JNK) and NF-kB activation were evaluated in J774.1 macrophages and CHO
      cells, respectively. RESULTS: LPGs were extracted, purified and analysed by
      western-blot, showing that LPG from L88 strain was longer than that of Cobaia
      strain. LPGs and GIPLs were depolymerised and their sugar content was determined.
      LPGs from both strains did not present side chains, having the common
      disaccharide Gal(beta1,4)Man(alpha1)-PO4. The GIPL from L88 strain presented
      galactose in its structure, suggestive of type II GIPL. On the other hand, the
      GIPL of Cobaia strain presented an abundance of glucose, a characteristic not
      previously observed. Mice peritoneal macrophages from C57BL/6 and knock-outs
      (TLR2 -/- and TLR4 -/-) were primed with IFN-gamma and stimulated with
      glycoconjugates and live parasites. No activation of NO or cytokines was observed
      with live parasites. On the other hand, LPGs and GIPLs were able to activate the
      production of NO, IL-6, IL-12 and TNF-alpha preferably via TRL2. However, in CHO
      cells, only GIPLs were able to activate TRL2 and TRL4. In vivo studies using male
      guinea pigs (Cavia porcellus) showed that only strain L88 was able to develop
      more severe ulcerated lesions especially in the presence of salivary gland
      extract (SGE). CONCLUSION: The two L. enriettii strains exhibited polymorphisms
      in their LPGs and GIPLs and those features may be related to a more pro
      inflammatory profile in the L88 strain.

PMID- 25595205
TI  - The role of lifestyle in perpetuating substance use disorder: the Lifestyle
      Balance Model.
AB  - Conceptualizing aetiology underpinning an individual's substance use disorder
      (SUD) not only facilitates insight and understanding, but also serves to identify
      targets for treatment and aid practitioners in selecting the most appropriate
      interventions. There is now a wealth of literature on aetiology and treatment
      approaches, and in more recent years, also literature to support the concept of
      'recovery' from a condition which was previously thought of as a chronic,
      relapsing condition. The burgeoning literature around research into recovery is
      revealing how recovery can best be defined and what factors might be associated
      with recovery from SUD. To add further to this growing body of literature, a new
      six-domain, explanatory biopsychosocial model of substance dependence and
      recovery, the Lifestyle Balance Model (LBM) is proposed. Based on research
      findings and theory reported in the literature, the LBM is a generic model
      depicting six domains of biopsychosocial functioning and includes within it the
      role of lifestyle. The LBM has been constructed as a domain model, allowing
      conceptualisation of the relationships between the six domain areas that
      perpetuate dependence and may also be associated with recovery from SUD,
      providing service users and clinicians with a tool for the delivery of case
      formulation and identification of target areas for intervention. 

PMID- 25595204
TI  - Characterisation and prognosis of undiagnosed chronic obstructive pulmonary
      disease patients at their first hospitalisation.
AB  - BACKGROUND: Under-diagnosis of COPD is an important unmet medical need. We
      investigated the characteristics and prognosis of hospitalised patients with
      undiagnosed COPD. METHODS: The PAC-COPD cohort included 342 COPD patients
      hospitalised for the first time for an exacerbation of COPD (2004-2006). Patients
      were extensively characterised using sociodemographic, clinical and functional
      variables, and the cohort was followed-up through 2008. We defined "undiagnosed
      COPD" by the absence of any self-reported respiratory disease and regular use of
      any pharmacological respiratory treatment. RESULTS: Undiagnosed COPD was present
      in 34% of patients. They were younger (mean age 66 vs. 68 years, p = 0.03),
      reported fewer symptoms (mMRC dyspnoea score, 2.1 vs. 2.6, p < 0.01), and had a
      better health status (SGRQ total score, 29 vs. 40, p < 0.01), milder airflow
      limitation (FEV1% ref., 59% vs. 49%, p < 0.01), and fewer comorbidities (two or
      more, 40% vs. 56%, p < 0.01) when compared with patients with an established COPD
      diagnosis. Three months after hospital discharge, 16% of the undiagnosed COPD
      patients had stopped smoking (vs. 5%, p = 0.019). During follow-up, annual
      hospitalisation rates were lower in undiagnosed COPD patients (0.14 vs. 0.25, p <
      0.01); however, this difference disappeared after adjustment for severity.
      Mortality was similar in both groups. CONCLUSIONS: Undiagnosed COPD patients have
      less severe disease and lower risk of re-hospitalisation when compared with
      hospitalised patients with known COPD.

PMID- 25595207
TI  - Drops on hydrophilic conical fibers: gravity effect and coexistent states.
AB  - Controlling the droplet equilibrium location and shape on a conical fiber is
      essential to industrial applications such as dip-pen nanolithography. In this
      work, the equilibrium conformations of a drop on a vertical, conical fiber has
      been investigated by the finite element method, Surface Evolver simulations.
      Similar to the morphology of a drop on a cylinder, two different types (barrel
      shape and clam-shell shape) can be obtained. In the absence of gravity, the
      droplet moves upward (lower curvature) and the total surface energy decays as the
      drop ascends. Whatever the initial conformation of the drop on a conical fiber,
      the rising drop exhibits the clam-shell shape eventually and there is no
      equilibrium location. However, in the presence of gravity, the drop can stop at
      the equilibrium location stably. For a given contact angle, the clam-shell shape
      is generally favored for smaller drops but the barrel shape is dominant for
      larger drops. In a certain range of drop volume, the coexistence of both barrel
      and clam-shell shapes is observed. For large enough drops, the falling-off state
      is seen. 

PMID- 25595206
TI  - Substance Use Across Different Phases of the Migration Process: A Survey of
      Mexican Migrants Flows.
AB  - This study examined the levels of substance use and changes across different
      migration stages, including pre-departure, travel, destination, and return, among
      Mexican migrants converging on the US-Mexico border. A cross-sectional survey was
      conducted in Tijuana, Mexico, between 2009 and 2010 among Mexican migrants
      returning from the US and those travelling from other Mexican regions. The
      overall prevalence of last 12-month at-risk drinking, illicit drug use, and
      current smoking, was 42.3, 17.7 and 31.4%, respectively. Compared to pre
      departure migrants, males were at increased risk for illicit drug use at the
      destination and return stages. In contrast, females' alcohol consumption at the
      destination stage was lower than at pre-departure (p < 0.05). The level of
      smoking was stable across all stages for both genders. In the destination stage,
      undocumented migrants were more likely to use illicit drugs relative to their
      documented peers (p < 0.05). Binational interventions promoting substance use
      reduction are needed among this mobile population.

PMID- 25595208
TI  - When the going gets tough the beautiful get going: aesthetic appeal facilitates
      task performance.
AB  - The current studies examined the effect of aesthetic appeal on performance.
      According to one hypothesis, appeal would lead to overall decrements or
      enhancements in performance [e.g. Sonderegger & Sauer, (Applied Ergonomics, 41,
      403-410, 2010)]. Alternatively, appeal might influence performance only in
      problem situations, such as when the task is difficult [e.g. Norman, (2004)]. The
      predictions of these hypotheses were examined in the context of an icon search
      and-localisation task. Icons were used because they are well-defined stimuli and
      pervasive to modern everyday life. When search was made difficult using visually
      complex stimuli (Experiment 1), or abstract and unfamiliar stimuli (Experiment
      2), icons that were appealing were found more quickly than their unappealing
      counterparts. These findings show that in a low-level visual processing task,
      with demand characteristics related to appeal eliminated, appeal can influence
      performance, especially under duress.

PMID- 25595209
TI  - Management of low-dose aspirin and clopidogrel in clinical practice: a
      gastrointestinal perspective.
AB  - Low-dose aspirin, alone or combined with other antiplatelet agents, is
      increasingly prescribed for cardiovascular prevention. However, the
      cardiovascular benefits should be evaluated together with the gastrointestinal
      risks. Low-dose aspirin is associated with upper and lower gastrointestinal
      injury, although lower gastrointestinal effects are poorly characterized. This
      gastrointestinal risk differs among antiplatelets drugs users. The most important
      risk factors are history of peptic ulcer, older age, and concomitant use of non
      steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper
      gastrointestinal prevention strategies are available and should be used in at
      risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem
      to be the best gastroprotective agents, whereas the benefits of Helicobacter
      pylori eradication are still unclear. Low-dose aspirin has additional effects in
      the gastrointestinal tract. A large body of evidence indicates that it can
      protect against different cancers, in particular colorectal cancer. This effect
      could modify the future indications for use of low-dose aspirin and the risk
      benefit balance. 

PMID- 25595210
TI  - Mitochondrially targeted Endonuclease III has a powerful anti-infarct effect in
      an in vivo rat model of myocardial ischemia/reperfusion.
AB  - Recent reports indicate that elevating DNA glycosylase/AP lyase repair enzyme
      activity offers marked cytoprotection in cultured cells and a variety of injury
      models. In this study, we measured the effect of EndoIII, a fusion protein
      construct that traffics Endonuclease III, a DNA glycosylase/AP lyase, to the
      mitochondria, on infarct size in a rat model of myocardial ischemia/reperfusion.
      Open-chest, anesthetized rats were subjected to 30 min of occlusion of a coronary
      artery followed by 2 h of reperfusion. An intravenous bolus of EndoIII, 8 mg/kg,
      just prior to reperfusion reduced infarct size from 43.8 +/- 1.4% of the risk
      zone in control animals to 24.0 +/- 1.3% with no detectable hemodynamic effect.
      Neither EndoIII's vehicle nor an enzymatically inactive EndoIII mutant (K120Q)
      offered any protection. The magnitude of EndoIII's protection was comparable to
      that seen with the platelet aggregation inhibitor cangrelor (25.0 +/- 1.8%
      infarction of risk zone). Because loading with a P2Y12 receptor blocker to
      inhibit platelets is currently the standard of care for treatment of acute
      myocardial infarction, we tested whether EndoIII could further reduce infarct
      size in rats treated with a maximally protective dose of cangrelor. The
      combination reduced infarct size to 15.1 +/- 0.9% which was significantly smaller
      than that seen with either cangrelor or EndoIII alone. Protection from cangrelor
      but not EndoIII was abrogated by pharmacologic blockade of phosphatidylinositol-3
      kinase or adenosine receptors indicating differing cellular mechanisms. We
      hypothesized that EndoIII protected the heart from spreading necrosis by
      preventing the release of proinflammatory fragments of mitochondrial DNA (mtDNA)
      into the heart tissue. In support of this hypothesis, an intravenous bolus at
      reperfusion of deoxyribonuclease I (DNase I) which should degrade any DNA
      fragments escaping into the extracellular space was as protective as EndoIII.
      Furthermore, the combination of EndoIII and DNase I produced additive protection.
      While EndoIII would maintain mitochondrial integrity in many of the ischemic
      cardiomyocytes, DNase I would further prevent mtDNA released from those cells
      that EndoIII could not save from propagating further necrosis. Thus, our mtDNA
      hypothesis would predict additive protection. Finally to demonstrate the toxicity
      of mtDNA, isolated hearts were subjected to 15 min of global ischemia. Infarct
      size doubled when the coronary vasculature was filled with mtDNA fragments during
      the period of global ischemia. To our knowledge, EndoIII and DNase are the first
      agents that can both be given at reperfusion and add to the protection of a P2Y12
      blocker, and thus should be effective in today's patient with acute myocardial
      infarction.

PMID- 25595211
TI  - Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells
      from cartilage, fat, and bone marrow in an ovine model of osteochondral focal
      defect.
AB  - Current developments in tissue engineering strategies for articular cartilage
      regeneration focus on the design of supportive three-dimensional scaffolds and
      their use in combination with cells from different sources. The challenge of
      translating initial successes in small laboratory animals into the clinics
      involves pilot studies in large animal models, where safety and efficacy should
      be investigated during prolonged follow-up periods. Here we present, in a single
      study, the long-term (up to 1 year) effect of biocompatible porous scaffolds non
      seeded and seeded with fresh ex vivo expanded autologous progenitor cells that
      were derived from three different cell sources [cartilage, fat and bone marrow
      (BM)] in order to evaluate their advantages as cartilage resurfacing agents. An
      ovine model of critical size osteochondral focal defect was used and the test
      items were implanted arthroscopically into the knees. Evidence of regeneration of
      hyaline quality tissue was observed at 6 and 12 months post-treatment with
      variable success depending on the cell source. Cartilage and BM-derived
      mesenchymal stromal cells (MSC), but not those derived from fat, resulted in the
      best quality of new cartilage, as judged qualitatively by magnetic resonance
      imaging and macroscopic assessment, and by histological quantitative scores.
      Given the limitations in sourcing cartilage tissue and the risk of donor site
      morbidity, BM emerges as a preferential source of MSC for novel cartilage
      resurfacing therapies of osteochondral defects using copolymeric poly-D,L-lactide
      co-glycolide scaffolds. 

PMID- 25595212
TI  - The innate immune response of equine bronchial epithelial cells is altered by
      training.
AB  - Respiratory diseases, including inflammatory airway disease (IAD), viral and
      bacterial infections, are common problems in exercising horses. The airway
      epithelium constitutes a major physical barrier against airborne infections and
      plays an essential role in the lung innate immune response mainly through toll
      like receptor (TLR) activation. The aim of this study was to develop a model for
      the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore
      EBEC innate immune responses in trained horses. Bronchial epithelial biopsies
      were taken from 6 adult horses during lower airway endoscopy. EBEC were grown in
      vitro by an explant method. The innate immune response of EBEC was evaluated in
      vitro by treatment with TLR ligands. TLR3 is the most strongly expressed TLR at
      the mRNA level in EBEC and stimulation of EBEC with Poly(I:C), an analog of viral
      dsRNA, triggers a strong secretion of IFN-beta, TNF-alpha, IL-6 and CXCL8. We
      further evaluated the EBEC innate immune response in horses that underwent a 4
      month-training program. While training had no effect on TLR mRNA expression in
      EBEC as well as in bronchial biopsies, it increased the production of IFN-beta
      after stimulation with a TLR3 ligand and decreased the secretion of TNF-alpha and
      IL-6 after stimulation with a TLR2 and TLR3 ligand. These findings may be
      implicated in the increased risk for viral and bacterial infections observed in
      sport horses. Altogether, we report a successful model for the culture of EBEC
      that can be applied to the investigation of pathophysiologic conditions in
      longitudinal studies. 

PMID- 25595213
TI  - Variation of resistance and infectivity between Pseudomonas fluorescens SBW25 and
      bacteriophage Phi2 and its therapeutic implications.

PMID- 25595214
TI  - Bacteriophage secondary infection.
AB  - Phages are credited with having been first described in what we now, officially,
      are commemorating as the 100(th) anniversary of their discovery. Those one
      hundred years of phage history have not been lacking in excitement, controversy,
      and occasional convolution. One such complication is the concept of secondary
      infection, which can take on multiple forms with myriad consequences. The terms
      secondary infection and secondary adsorption, for example, can be used almost
      synonymously to describe virion interaction with already phage-infected bacteria,
      and which can result in what are described as superinfection exclusion or
      superinfection immunity. The phrase secondary infection also may be used
      equivalently to superinfection or coinfection, with each of these terms borrowed
      from medical microbiology, and can result in genetic exchange between phages,
      phage-on-phage parasitism, and various partial reductions in phage productivity
      that have been termed mutual exclusion, partial exclusion, or the depressor
      effect. Alternatively, and drawing from epidemiology, secondary infection has
      been used to describe phage population growth as that can occur during active
      phage therapy as well as upon phage contamination of industrial ferments. Here
      primary infections represent initial bacterial population exposure to phages
      while consequent phage replication can lead to additional, that is, secondary
      infections of what otherwise are not yet phage-infected bacteria. Here I explore
      the varying meanings and resultant ambiguity that has been associated with the
      term secondary infection. I suggest in particular that secondary infection, as
      distinctly different phenomena, can in multiple ways influence the success of
      phage-mediated biocontrol of bacteria, also known as, phage therapy. 

PMID- 25595215
TI  - Magnetic resonance imaging for acute hip pain in the emergency department.
AB  - MRI is an excellent imaging modality for the evaluation of acute hip pain in the
      ED and provides accurate diagnosis; facilitating appropriate and timely
      management thereby can result in decreased cost and improved prognosis in these
      patients. In this article, we review the use of MRI for patients presenting with
      acute hip pain in the Emergency Department (ED), including MRI protocols, MRI
      features of common acute hip pathologies, pivotal differential diagnoses, and
      management options. 

PMID- 25595217
TI  - Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a
      Community from India.
AB  - Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis,
      requiring either invasive liver biopsy-enzyme assay or potentially hazardous
      fructose challenge test or expensive molecular genetic analysis. Therefore,
      worldwide there has been a trend towards finding "common mutations" in distinct
      ethnic groups to simplify the process of diagnosis. The nonspecific presentation
      of the disease often leads to diagnostic confusion with other metabolic liver
      disorders such as glycogenoses, galactosemia, and tyrosinemia. This leads to much
      delay in diagnosis with consequent harm to the patient.We report mutations in the
      ALDOB gene, from eleven Indian patients, seven of whom belong to the Agarwal
      community. Six patients from the Agarwal community and two non-Agarwal patients
      harbored one novel mutation, c.324+1G>A (five homozygous and one heterozygous),
      in the ALDOB gene. Haplotyping performed in families confirmed a founder effect.
      The community has been known to harbor founder mutations in other genes such as
      the MLC1, PANK2, and CAPN3 genes, thus providing another evidence for a founder
      effect in the community in case of HFI. This may pave the path for a simpler and
      quicker test at least for this community in India. In addition to the founder
      mutation, we report four other novel mutations, c.112+1delG, c.380-1G>A,
      c.677G>A, and c.689delA, and a previously reported mutation, c.1013C>T, in the
      cohort from India. 

PMID- 25595216
TI  - [Intervertebral cages from a biomechanical point of view].
AB  - BACKGROUND: If lumbar interbody fusion is indicated, there are several options
      for instrumentation of the affected motion segment. Intervertebral cages are
      implanted in the disc to restore disc height and to stabilize the motion segment
      by tensioning the ligamentous structures. METHODS: Based on a selective
      literature search with the focus on biomechanical aspects of intervertebral
      cages, experimental and clinical studies are shown, interpreted, and discussed.
      RESULTS: In the literature, biomechanical flexibility tests of "stand alone"
      cages without supplemental instrumentation showed a limited stabilizing effect,
      particularly in extension and axial rotation, as well as an increased load
      transfer through the ventral column. Applying supplemental dorsal instrumentation
      can return the ventral/dorsal load sharing to the range of an intact motion
      segment and causes a marked increase of stability in all motion planes. Compared
      to bilateral dorsal instrumentation, unilateral dorsal instrumentation showed a
      reduced primary stability and leads to an asymmetrical loading of the cage which
      can cause unilateral loss of reduction. Nonmetallic cages with a stiffness
      adapted to bone allow better radiological evaluation of the bony fusion of the
      motion segment and theoretically have a reduced tendency to migrate. CONCLUSION:
      In combination with bilateral dorsal instrumentation, cage geometry and material
      have only a minor influence on primary stability and the main stability is
      provided by the internal fixator.

PMID- 25595218
TI  - Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and
      laryngeal squamous cell carcinoma: mature treatment results and patterns of
      locoregional failure.
AB  - PURPOSE: To assess clinical outcomes and patterns of loco-regional failure (LRF)
      in relation to clinical target volumes (CTV) in patients with locally advanced
      hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with
      definitive intensity modulated radiotherapy (IMRT) and concurrent systemic
      therapy. METHODS: Data from HL-SCC patients treated from 2007 to 2010 were
      retrospectively evaluated. Primary endpoint was loco-regional control (LRC).
      Secondary endpoints included local (LC) and regional (RC) controls, distant
      metastasis free survival (DMFS), laryngectomy free survival (LFS), overall
      survival (OS), and acute and late toxicities. Time-to-event endpoints were
      estimated using Kaplan-Meier method, and univariate and multivariate analyses
      were performed using Cox proportional hazards models. Recurrent gross tumor
      volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to
      corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20-95% inside
      CTV; out-volume, < 20% inside CTV). RESULTS: Fifty patients (stage III: 14, IVa:
      33, IVb: 3) completed treatment and were included in the analysis (median follow
      up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96%
      and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%,
      respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We
      identified 10 patients with LRF (8 local, 1 regional, 1 local + regional). Six
      out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4
      RTVs were marginal to the high-dose CTVs. CONCLUSION: The treatment of locally
      advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides
      good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of
      LRFs in relation to CTVs showed in-volume relapses to be the major mode of
      recurrence indicating that novel strategies to overcome radioresistance are
      required.

PMID- 25595219
TI  - Weekday and weekend patterns of objectively measured sitting, standing, and
      stepping in a sample of office-based workers: the active buildings study.
AB  - BACKGROUND: There is a growing body of research into the total amount and
      patterns of sitting, standing and stepping in office-based workers and few
      studies using objectively measured sitting and standing. Understanding these
      patterns may identify daily times opportune for interventions to displace sitting
      with activity. METHODS: A sample of office-based workers (n = 164) residing in
      England were fitted with thigh-worn ActivPal accelerometers and devices were worn
      24 hours a day for five consecutive days, always including Saturday and Sunday
      and during bathing and sleeping. Daily amounts and patterns of time spent
      sitting, standing, stepping and step counts and frequency of sit/stand
      transitions, recorded by the ActivPal accelerometer, were reported. RESULTS:
      Total sitting/standing time was similar on weekdays (10.6/4.1 hrs) and weekends
      (10.6/4.3 hrs). Total step count was also similar over weekdays (9682 +/- 3872)
      and weekends (9518 +/- 4615). The highest physical activity levels during
      weekdays were accrued at 0700 to 0900, 1200 to 1400, and 1700 to 1900; and during
      the weekend at 1000 to 1700. During the weekday the greatest amount of sitting
      was accrued at 0900 to 1200, 1400 to 1700, and 2000 to 2300, and on the weekend
      between 1800 and 2300. During the weekday the greatest amount of standing was
      accrued between 0700 and 1000 and 1700 and 2100, and on the weekend between 1000
      and 1800. On the weekday the highest number of sit/stand transitions occurred
      between 0800 to 0900 and remained consistently high until 1800. On the weekend,
      the highest number occurred between 1000 to 1400 and 1900 to 2000. CONCLUSION:
      Office based-workers demonstrate high levels of sitting during both the working
      week and weekend. Interventions that target the working day and the evenings
      (weekday and weekend) to displace sitting with activity may offer most promise
      for reducing population levels of sedentary behaviour and increasing physical
      activity levels, in office-based workers residing in England.

PMID- 25595220
TI  - Achievement of metabolic control goals set by the American Diabetes Association
      and the International Society for Pediatric and Adolescent Diabetes in pediatric
      patients with type 1 diabetes from Spain.
AB  - AIM: The "T1D Exchange Clinic Registry" of 13.316 pediatric patients with type 1
      diabetes (T1D) in U.S. recently revealed that most children have HbA1c values
      above target levels established by the American Diabetes Association (ADA) and
      the International Society for Pediatric and Adolescent Diabetes (ISPAD). The aim
      of this study is to assess the proportion of youngsters with T1D who meet the
      internationally accepted targets for good metabolic control of diabetes at a
      single, referral Pediatric Diabetes Center in Spain. PATIENTS AND METHODS: Cross
      sectional study of 236 children and adolescents with T1D controlled at our
      Pediatric Diabetes Unit. We analyzed the compliance to metabolic goals set by ADA
      and ISPAD and the differences between patients treated with continuous
      subcutaneous insulin infusion and multiple daily injections. STATISTICS: SPSSTM
      version 21.0. RESULTS: Mean age: 12.6 +/- 4.6 years old, mean age at diagnosis:
      6.1 +/- 4.3 years old and mean diabetes duration: 6.4 +/- 4.3 years; 47% female.
      HbA1c average: 6.7 +/- 0.7% (49.7 +/- 7.6 mmol/mol). The age-specific ADA and
      ISPAD HbA1c targets were achieved by 93% and 91% of patients, respectively. Among
      pump users, 97%/97% met ADA/ISPAD HbA1c targets compared to 87%/88% of MDI users
      (p = 0.04/p = 0.03), without significant differences in the analysis by groups of
      age. Among participants, 95%, 62%, 95%, 98% and 89% met HDLc, LDLc,
      triglycerides, BP and BMI targets. CONCLUSIONS: Most patients in our children and
      adolescent cohort of T1D patients correctly achieve metabolic goals established
      by ADA and ISPAD with low incidence of hypoglycemia.

PMID- 25595221
TI  - Primary results from the cervical dystonia patient registry for observation of
      onabotulinumtoxina efficacy (CD PROBE).
AB  - BACKGROUND: The Cervical Dystonia Patient Registry for Observation of
      OnabotulinumtoxinA Efficacy (CD PROBE; NCT00836017) is a prospective,
      observational, multicenter, real-world registry designed to assess the safety,
      effectiveness, and treatment utilization following multiple treatments of
      onabotulinumtoxinA. METHODS: Subjects were naive to botulinum toxin, new to
      practice, or had not received toxin in >= 16 weeks if in a clinical trial.
      Dosages and treatment intervals varied due to the real-world design. Descriptive
      and inferential statistics evaluated changes over 3 treatments. RESULTS: 1046
      subjects enrolled. Subjects were 74.4% female, 63.5% toxin-naive, mean age 58.0
      +/- 14.7 years. The mean dose over 2481 treatment sessions was 189. 8 +/- 87.1U,
      with average treatment intervals of 14.6 and 15.1 weeks. The mean Toronto Western
      Spasmodic Torticollis Rating Scale Total score in subjects who completed all
      assessments (n=479) decreased from 39.2 at baseline to 27.1 at final visit
      (P<.0001). A high percentage of physicians reported improvement in Clinician
      Global Impression of Change after initial assessment; this significantly
      increased at final assessment (n=479, 91.2% vs 95.0%; P<.0001). Similarly, a high
      percentage of subjects reported improvement in Patient Global Impression of
      Change after initial assessment, which significantly increased at final
      assessment (n=470, 83.0% vs 91.7%; P<.0001). Significant reductions in all
      Cervical Dystonia Impact Profile-58 scores were observed (n=407). Overall, 26.2%
      of subjects reported adverse events, including muscular weakness (7.0%) and
      dysphagia (6.4%). CONCLUSIONS: Results indicate robust improvement in clinical
      ratings and excellent tolerability following onabotulinumtoxinA treatment of CD.

PMID- 25595222
TI  - Comparison of grey matter volume and thickness for analysing cortical changes in
      chronic schizophrenia: a matter of surface area, grey/white matter intensity
      contrast, and curvature.
AB  - Grey matter volume and cortical thickness are the two most widely used measures
      for detecting grey matter morphometric changes in various diseases such as
      schizophrenia. However, these two measures only share partial overlapping regions
      in identifying morphometric changes. Few studies have investigated the
      contributions of the potential factors to the differences of grey matter volume
      and cortical thickness. To investigate this question, 3T magnetic resonance
      images from 22 patients with schizophrenia and 20 well-matched healthy controls
      were chosen for analyses. Grey matter volume and cortical thickness were measured
      by VBM and Freesurfer. Grey matter volume results were then rendered onto the
      surface template of Freesurfer to compare the differences from cortical thickness
      in anatomical locations. Discrepancy regions of the grey matter volume and
      thickness where grey matter volume significantly decreased but without
      corresponding evidence of cortical thinning involved the rostral middle frontal,
      precentral, lateral occipital and superior frontal gyri. Subsequent region-of
      interest analysis demonstrated that changes in surface area, grey/white matter
      intensity contrast and curvature accounted for the discrepancies. Our results
      suggest that the differences between grey matter volume and thickness could be
      jointly driven by surface area, grey/white matter intensity contrast and
      curvature. 

PMID- 25595223
TI  - Ligand and structure-based approaches for the identification of SIRT1 activators.
AB  - SIRT1 is a NAD(+)-dependent deacetylase that involved in various important
      metabolic pathways. Combined ligand and structure-based approach was utilized for
      identification of SIRT1 activators. Pharmacophore models were developed using
      DISCOtech and refined with GASP module of Sybyl X software. Pharmacophore models
      were composed of two hydrogen bond acceptor (HBA) atoms, two hydrogen bond donor
      (HBD) sites and one hydrophobic (HY) feature. The pharmacophore models were
      validated through receiver operating characteristic (ROC) and Guner-Henry (GH)
      scoring methods. Model-2 was selected as best model among the model 1-3, based on
      ROC and GH score value, and found reliable in identification of SIRT1 activators.
      Model-2 (3D search query) was searched against Zinc database. Several compounds
      with different chemical scaffold were retrieved as hits. Currently, there is no
      experimental SIRT1 3D structure available, therefore, we modeled SIRT1 protein
      structure using homology modeling. Compounds with Qfit value of more than 86 were
      selected for docking study into the SIRT1 homology model to explore the binding
      mode of retrieved hits in the active allosteric site. Finally, in silico ADMET
      prediction study was performed with two best docked compounds. Combination of
      ligand and structure-based modeling methods identified active hits, which may be
      good lead compounds to develop novel SIRT1 activators. 

PMID- 25595224
TI  - Modulating inhibitors of transthyretin fibrillogenesis via sulfation:
      polychlorinated biphenyl sulfates as models.
AB  - Small molecules that bind with high affinity to thyroxine (T4) binding sites on
      transthyretin (TTR) kinetically stabilize the protein's tetrameric structure,
      thereby efficiently decreasing the rate of tetramer dissociation in TTR related
      amyloidoses. Current research efforts aim to optimize the amyloid inhibiting
      properties of known inhibitors, such as derivatives of biphenyls, dibenzofurans
      and benzooxazoles, by chemical modification. In order to test the hypothesis that
      sulfate group substituents can improve the efficiencies of such inhibitors, we
      evaluated the potential of six polychlorinated biphenyl sulfates to inhibit TTR
      amyloid fibril formation in vitro. In addition, we determined their binding
      orientations and molecular interactions within the T4 binding site by molecular
      docking simulations. Utilizing this combined experimental and computational
      approach, we demonstrated that sulfation significantly improves the amyloid
      inhibiting properties as compared to both parent and hydroxylated PCBs.
      Importantly, several PCB sulfates were of equal or higher potency than some of
      the most effective previously described inhibitors. 

PMID- 25595226
TI  - Carbonyl-reducing enzymes as targets of a drug-immobilised affinity carrier.
AB  - Proteins, peptides and nucleic acids are commonly isolated and purified in almost
      all bioscience laboratories. Methods based on molecular recognition are currently
      the most powerful tool in separation processes due to their selectivity and
      recovery. The aim of this study was to prove the versatility and the ability of
      an affinity carrier containing the immobilised ligand oracin (previously
      developed by our workgroup) to selectively bind carbonyl-reducing enzymes. These
      enzymes play an important role in metabolic pathways of various endogenic
      compounds and xenobiotics. Many important drugs, such as doxorubicin,
      daunorubicin, haloperidol and the model anticancer drug oracin, are metabolised
      by carbonyl-reducing enzymes. The functionality of the presented carrier was
      demonstrated with pure recombinant enzymes (AKR1A1, AKR1B1, AKR1B10, AKR1C1,
      AKR1C2, AKR1C3, AKR1C4, CBR1 and CBR3) as well as with two model biological
      samples (cell extract from genetically modified Escherichia coli and pre-purified
      human liver cytosol). Enzymes that show an affinity toward oracin were
      efficiently captured, gently eluted using 150 mM ammonium hydroxide and
      subsequently identified by MS. The method is highly selective and robust and may
      be applied to the purification and identification of various carbonyl-reducing
      enzymes from any biological sample.

PMID- 25595225
TI  - Cloning and characterization of a novel beta-ketoacyl-ACP reductase from
      Comamonas testosteroni.
AB  - Comamonas testosteroni (C. testosteroni) is a gram negative bacterium which can
      use steroid as a carbon source and degrade steroid with about 20 special enzymes.
      Most of the enzymes are inducible enzymes. 3-Oxoacyl-ACP reductase (E.C.
      1.1.1.100) alternatively known as beta-ketoacyl-ACP reductase (BKR) is involved
      in fatty acid syntheses. DNA sequence comparison showed that BKR belongs to the
      short-chain alcohol dehydrogenase (SDR) family. Our results showed that BKR is
      necessary for the degradation of steroid hormones in C. testosteroni. The DNA
      fragment of the BKR gene was cloned into an expressional plasmid pET-15b. BKR
      protein was expressed with 6* His-tag on the N-terminus and the enzyme was
      purified with Ni-column. Antibodies against BKR were prepared and a new BKR
      quantitative ELISA was created in our laboratory. The purified BKR is a 30.6 kDa
      protein on SDS-PAGE. C. testosteroni was induced by testosterone, estradiol,
      estriol and cholesterol. The expression of BKR was detected with an ELISA. The
      result showed that the BKR expression could be induced by cholesterol and estriol
      but not by testosterone and estradiol. BKR gene knock-out mutant (M-C.T.) was
      prepared by homologous integration. High performance liquid chromatography (HPLC)
      was used to detect steroid hormone degradation in C. testosteroni ATCC11996 and
      BKR gene knock-out mutant. We proved that the M-C.T. eliminated of testosterone
      degradation. Degradations of cholesterol and estradiol were also decreased. We
      conclude that the novel BKR in C. testosteroni plays an important role in steroid
      degradation. This work provides some new information of SDR and steroid
      degradation in C. testosteroni.

PMID- 25595227
TI  - Characterization of 3,17beta-hydroxysteroid dehydrogenase in Comamonas
      testosteroni.
AB  - 3,17beta-Hydroxysteroid dehydrogenases (3,17beta-HSDs) are found in all forms of
      life which catalyze the 3-position and 17-position reduction/oxidation of
      steroids. Comamonas testosteroni (C. testosteroni) ATCC11996 is a gram-negative
      bacterium which can use steroids as carbon and energy source. 3,17beta-HSD is an
      enzyme which is involved in the complete oxidative degradation of the steroid
      skeleton, induced in the presence of these compounds in the culture medium.
      Cyclizing RT-PCR (cRT-PCR) was used to investigate the transcription start site
      (TSS) and promoter of 3,17beta-HSD gene. To prove that 3,17beta-HSD is involved
      in the metabolic pathway of steroid compounds, we prepared a 3,17beta-HSD gene
      knock-out mutant and a mutant of C. testosteroni in which 3,17beta-HSD was
      expressed at high level. The results indicate that 3,17beta-HSD gene expression
      was induced by testosterone, but not by estradiol and cholesterol. Compared to
      the wild type C. testosteroni, degradation ability of testosterone and
      cholesterol was almost lost, and degradation of estradiol was decreased in the
      3,17beta-HSD knock-out mutant. Meanwhile degradation of testosterone, cholesterol
      was obviously increased in the 3,17beta-HSD high expression mutant. Furthermore,
      the growths in the medium with testosterone, cholesterol or estradiol were
      impaired in 3,17beta-HSD knock-out mutant. The results showed that in addition to
      testosterone and estradiol, 3,17beta-HSD might be also involved in cholesterol
      metabolism. The location of the TSS and promoter of the 3,17beta-HSD gene were
      found in this work. 

PMID- 25595228
TI  - Can we use social media to support content validity of patient-reported outcome
      instruments in medical product development?
AB  - We report a panel designed to open a dialog between pharmaceutical sponsors,
      regulatory reviewers, and other stakeholders regarding the use of social media to
      collect data to support the content validity of patient-reported outcome
      instruments in the context of medical product labeling. Multiple stakeholder
      perspectives were brought together to better understand the issues encountered in
      pursuing social media as a form of data collection to support content validity.
      Presenters represented a pharmaceutical sponsor of clinical trials, a regulatory
      reviewer from the Food and Drug Administration, and an online data platform
      provider. Each presenter shared its perspective on the advantages and
      disadvantages of using social media to collect this type of information. There
      was consensus that there is great potential for using social media for this
      purpose. There remain, however, unanswered questions that need to be addressed
      such as identifying which type of social media is most appropriate for data
      collection and ensuring that participants are representative of the target
      population while maintaining the advantages of anonymity provided by online
      platforms. The use of social media to collect evidence of content validity holds
      much promise. Clarification of issues that need to be addressed and accumulation
      of empirical evidence to address these questions are essential to moving forward.

PMID- 25595229
TI  - Applying dynamic simulation modeling methods in health care delivery research-the
      SIMULATE checklist: report of the ISPOR simulation modeling emerging good
      practices task force.
AB  - Health care delivery systems are inherently complex, consisting of multiple tiers
      of interdependent subsystems and processes that are adaptive to changes in the
      environment and behave in a nonlinear fashion. Traditional health technology
      assessment and modeling methods often neglect the wider health system impacts
      that can be critical for achieving desired health system goals and are often of
      limited usefulness when applied to complex health systems. Researchers and health
      care decision makers can either underestimate or fail to consider the
      interactions among the people, processes, technology, and facility designs.
      Health care delivery system interventions need to incorporate the dynamics and
      complexities of the health care system context in which the intervention is
      delivered. This report provides an overview of common dynamic simulation modeling
      methods and examples of health care system interventions in which such methods
      could be useful. Three dynamic simulation modeling methods are presented to
      evaluate system interventions for health care delivery: system dynamics, discrete
      event simulation, and agent-based modeling. In contrast to conventional
      evaluations, a dynamic systems approach incorporates the complexity of the system
      and anticipates the upstream and downstream consequences of changes in complex
      health care delivery systems. This report assists researchers and decision makers
      in deciding whether these simulation methods are appropriate to address specific
      health system problems through an eight-point checklist referred to as the
      SIMULATE (System, Interactions, Multilevel, Understanding, Loops, Agents, Time,
      Emergence) tool. It is a primer for researchers and decision makers working in
      health care delivery and implementation sciences who face complex challenges in
      delivering effective and efficient care that can be addressed with system
      interventions. On reviewing this report, the readers should be able to identify
      whether these simulation modeling methods are appropriate to answer the problem
      they are addressing and to recognize the differences of these methods from other
      modeling approaches used typically in health technology assessment applications. 

PMID- 25595230
TI  - High-dose hemodialysis versus conventional in-center hemodialysis: a cost-utility
      analysis from a UK payer perspective.
AB  - OBJECTIVE: To investigate the cost-effectiveness of high-dose hemodialysis (HD)
      versus conventional in-center HD (ICHD), over a lifetime time horizon from the UK
      payer's perspective. METHODS: We used a Markov modeling approach to compare high
      dose HD (in-center or at home) with conventional ICHD using current and
      hypothetical home HD reimbursement tariffs in England. Sensitivity analyses
      tested the robustness of the results. The main outcome measure was the
      incremental cost-effectiveness ratio (ICER) expressed as a cost per quality
      adjusted life-year (QALY). RESULTS: Over a lifetime, high-dose HD in-center (5
      sessions/wk) is associated with higher per-patient costs and QALYs (increases of
      L108,713 and 0.862, respectively) versus conventional ICHD. The corresponding
      ICER (L126,106/QALY) indicates that high-dose HD in-center is not cost-effective
      versus conventional ICHD at a UK willingness-to-pay threshold of L20,000 to
      L30,000. High-dose HD at home is associated with lower total costs (L522 less per
      patient) and a per-patient QALY increase of 1.273 compared with ICHD under the
      current Payment-by Results reimbursement tariff (L456/wk). At an increased home
      HD tariff (L575/wk), the ICER for high-dose HD at home versus conventional ICHD
      is L17,404/QALY. High-dose HD at home had a 62% to 84% probability of being cost
      effective at a willingness-to-pay threshold of L20,000 to L30,000/QALY.
      CONCLUSIONS: Although high-dose HD has the potential to offer improved clinical
      and quality-of-life outcomes over conventional ICHD, under the current UK Payment
      by Results reimbursement scheme, it would be considered cost-effective from a UK
      payer perspective only if conducted at home.

PMID- 25595231
TI  - Using classical test theory, item response theory, and Rasch measurement theory
      to evaluate patient-reported outcome measures: a comparison of worked examples.
AB  - OBJECTIVE: To provide comparisons and a worked example of item- and scale-level
      evaluations based on three psychometric methods used in patient-reported outcome
      development-classical test theory (CTT), item response theory (IRT), and Rasch
      measurement theory (RMT)-in an analysis of the National Eye Institute Visual
      Functioning Questionnaire (VFQ-25). METHODS: Baseline VFQ-25 data from 240
      participants with diabetic macular edema from a randomized, double-masked,
      multicenter clinical trial were used to evaluate the VFQ at the total score
      level. CTT, RMT, and IRT evaluations were conducted, and results were assessed in
      a head-to-head comparison. RESULTS: Results were similar across the three
      methods, with IRT and RMT providing more detailed diagnostic information on how
      to improve the scale. CTT led to the identification of two problematic items that
      threaten the validity of the overall scale score, sets of redundant items, and
      skewed response categories. IRT and RMT additionally identified poor fit for one
      item, many locally dependent items, poor targeting, and disordering of over half
      the response categories. CONCLUSIONS: Selection of a psychometric approach
      depends on many factors. Researchers should justify their evaluation method and
      consider the intended audience. If the instrument is being developed for
      descriptive purposes and on a restricted budget, a cursory examination of the CTT
      based psychometric properties may be all that is possible. In a high-stakes
      situation, such as the development of a patient-reported outcome instrument for
      consideration in pharmaceutical labeling, however, a thorough psychometric
      evaluation including IRT or RMT should be considered, with final item-level
      decisions made on the basis of both quantitative and qualitative results.

PMID- 25595232
TI  - Comparing measurement properties of the EQ-5D-3L, ICECAP-O, and ASCOT in frail
      older adults.
AB  - BACKGROUND: The ICEpop CAPability measure for Older people (ICECAP-O) and the
      Adult Social Care Outcomes Toolkit (ASCOT) are preference-based measures for
      assessing quality of life (QOL) from a broader perspective than do traditional
      health-related QOL measures such as the EuroQol five-dimensional questionnaire
      (EQ-5D). Measurement properties of these instruments have not yet been directly
      compared. OBJECTIVE: The purpose of this study was to compare the test-retest
      reliability, construct validity, and responsiveness of the three-level EQ-5D (EQ
      5D-3L), ICECAP-O, and ASCOT in frail older adults living at home. METHODS: Cross
      sectional data and longitudinal data were used. Parameters for reliability (the
      intraclass correlation coefficient) and agreement (standard error of measurement)
      were used to assess test-retest reliability after 1 week. We formulated
      hypotheses about correlations with other measures and tested these to assess
      construct validity and responsiveness (longitudinal validity). RESULTS: The
      reliability parameters for all three scales were considered good (intraclass
      correlation coefficient values above 0.70). Standard error of measurement values
      were less than 10% of the scale. Hypotheses regarding construct validity were in
      general accepted; the EQ-5D-3L was more strongly associated with physical
      limitations than were ICECAP-O and ASCOT and less strongly with instruments
      measuring aspects beyond health. Longitudinally, as hypothesized, mental health
      was most strongly associated with ICECAP-O, and self-perceived QOL, mastery, and
      client-centeredness of home care most strongly with ASCOT. CONCLUSIONS: Our
      findings support the adoption of ICECAP-O and ASCOT as outcome measures in
      economic evaluations of care interventions for older adults that have a broader
      aim than health-related QOL because they are at least as reliable as the EQ-5D-3L
      and are associated with aspects of QOL broader than health.

PMID- 25595233
TI  - Measuring health-related quality of life by experiences: the experience sampling
      method.
AB  - OBJECTIVE: To explore the potential value of obtaining momentary, instead of
      retrospective, accounts of the description and valuation of a person's own health
      related quality of life (HRQOL). METHODS: Momentary HRQOL was examined with the
      experience sampling method (ESM) in 139 participants from four different samples.
      The ESM consists of a so-called beep questionnaire that was administered 10 times
      a day by an electronic device. Feasibility was determined by assessing
      willingness to participate in the study and by analyzing the percentage of
      dropouts and the number of completed beep questionnaires. Multilevel analysis was
      used to investigate the relation between momentary HRQOL and momentary feelings
      and symptoms. The relation between momentary outcomes and the EuroQol visual
      analogue scale was investigated with a multiple regression model. RESULTS: The
      overall participation rate was low, but there were no dropouts and the number of
      completed beeps was comparable to that in other studies. Multilevel analysis
      showed that feelings and symptoms were significant predictors of momentary HRQOL.
      The strength of these relations differed among three patient groups and a
      population-based sample. The EuroQol visual analogue scale was not predicted by
      momentary feelings and symptoms. CONCLUSIONS: We can conclude that the use of the
      ESM to measure accounts of the momentary experience of health in different
      populations is feasible. Retrospective measures may provide a biased account of
      the impact of health problems in the daily lives of people who are affected.
      Moreover, the bias may be different in different conditions.

PMID- 25595234
TI  - An exploratory study to test the impact on three "bolt-on" items to the EQ-5D.
AB  - BACKGROUND: Generic preference-based measures were criticized for being
      inappropriate in some conditions. One solution is to include "bolt-on" dimensions
      describing additional specific health problems. OBJECTIVES: This study aimed to
      develop bolt-on dimensions to the EuroQol five-dimensional questionnaire (EQ-5D)
      and assess their impact on health state values. METHODS: Bolt-on dimensions were
      developed for vision problems, hearing problems, and tiredness. Each bolt-on
      dimension had three severity levels to match the EQ-5D. Three "core" EQ-5D states
      across a range of severity were selected, and each level of a bolt-on item was
      added, resulting in nine states in each condition. Health states with and without
      the bolt-on dimensions were valued by 300 members of the UK general public using
      time trade-off in face-to-face interviews, and mean health state values were
      compared using t tests. Regression analysis examined the impact of the bolt-on
      variants and the level of the bolt-on items after controlling for
      sociodemographic characteristics. RESULTS: Bolt-on dimensions had an impact on
      health state values of the EQ-5D; however, the size, direction, and significance
      of the impact depend on the severity of the core EQ-5D state and of the bolt-on
      dimension. Regression analysis demonstrated that after controlling for possible
      differences in sociodemographic characteristics between the groups, there were no
      significant differences in health state values between the three bolt-on
      dimensions but confirmed that the impact depended on the severity of the EQ-5D
      health state and the levels of bolt-on dimensions. CONCLUSIONS: The impact of a
      bolt-on dimension on the EQ-5D depends on the core health state and the level of
      the bolt-on dimension. Further research in this area is encouraged.

PMID- 25595235
TI  - Estimating quality-adjusted life-year loss due to noncommunicable diseases in
      Korean adults through to the year 2040.
AB  - OBJECTIVES: To estimate the loss in quality-adjusted life-years (QALYs) in Korean
      adults due to 13 noncommunicable diseases (NCDs) in 2010 and predict changes in
      QALY loss through to the year 2040. METHODS: Thirteen NCDs (hypertension,
      diabetes mellitus, hyperlipidemia, stroke, myocardial infarction, angina,
      arthritis, osteoporosis, asthma, allergic rhinitis, atopic dermatitis, cataract,
      and depression) were selected from the Korean Community Health Survey 2010. The
      EuroQol five-dimensional questionnaire index from the Korean Community Health
      Survey 2010 and the Korean valuation set were used to estimate utility weights
      according to sex, age, and disease. Morbidity data were also obtained from the
      Korean Community Health Survey 2010. Mortality data according to disease and life
      expectancy were retrieved from the Korean Statistical Information Service. To
      predict future QALY loss, future population projection data from the Korean
      Statistical Information Service were used as substitutes for 2010 population
      size. RESULTS: Among the assessed 13 NCDs, the largest total QALY loss was for
      hypertension (513,113 QALYs; units are omitted hereafter), followed by arthritis
      (509,317) and stroke (431,049). The largest QALY loss due to mortality was stroke
      (306,733), whereas the largest QALY loss due to morbidity was arthritis
      (502,513). By applying the middle estimate of future population, the largest
      increase in total QALY loss between 2010 and 2040 was for hypertension (840,582),
      followed by stroke (719,076) and diabetes mellitus (474,607). CONCLUSIONS:
      Hypertension, arthritis, and stroke are important in terms of total QALY loss,
      which will continuous to increase because of aging. These results could be used
      to develop cost-effective interventions that reduce the burden of NCDs.

PMID- 25595236
TI  - Pediatricians' preferences for infant meningococcal vaccination.
AB  - BACKGROUND: Meningococcal disease is rare but can cause death or disabilities.
      Although the Advisory Committee on Immunization Practices has recommended
      meningococcal vaccination for at-risk children aged 9 through 23 months, it has
      not endorsed universal vaccination. Health insurance payments for the vaccination
      of children who are not at risk are likely to be limited. Use of infant
      meningococcal vaccines by these families will thus depend on the preferences of
      physicians who might recommend vaccination to parents, as well as parents'
      preferences. OBJECTIVE: To quantify pediatricians' preferences for specific
      features of hypothetical infant meningococcal vaccines. METHODS: A sample of
      pediatricians (n = 216) completed a Web-enabled, discrete choice experiment
      survey in which respondents chose between pairs of hypothetical vaccines in a
      series of trade-off questions. The questions described vaccines with six
      attributes. A random-parameters logit regression model was used to estimate the
      relative importance weights physicians place on vaccine features. These weights
      were used to calculate the predicted probability that a physician chooses
      hypothetical vaccines with given characteristics. RESULTS: Pediatricians' choices
      indicated that increases in vaccine effectiveness were among the most important
      factors in their vaccine recommendations, followed by increases in the number of
      injections. The age at which protection begins and the number of additional
      office visits were less important. Whether a booster was required after 5 years
      was the least important factor in vaccine recommendations. The results suggest
      that virtually all (99.9%) physicians in the sample would recommend a vaccine
      even with the least-preferred features rather than no infant meningococcal
      vaccine. CONCLUSIONS: Physicians' responses indicate a strong preference for
      infant meningococcal vaccination.

PMID- 25595237
TI  - Physicians' preferences for bone metastases drug therapy in the United States.
AB  - OBJECTIVE: Several characteristics of bone-targeted agents are considered when
      making treatment decisions. This study evaluated physicians' therapy preferences
      for preventing skeletal-related events (SREs) in patients with bone metastases
      secondary to solid tumors. METHODS: A Web-enabled, discrete-choice experiment
      online survey was conducted among physicians who treated patients with bone
      metastases and solid tumors in the United States. Respondents chose between pairs
      of hypothetical medications defined by combinations of six attributes at varying
      levels for two hypothetical patients. Preference weights for attribute levels
      were estimated using a random-parameters logit model. RESULTS: In total, 200
      physicians completed the survey. Their mean age was 52 years, 57% were in
      practice for more than 15 years, 37% were oncologists, and 65% treated 10 or
      fewer patients with bone metastases weekly. Out-of-pocket cost to patients was
      the most important attribute overall. Among clinical outcomes, time to first SRE
      and risk of renal impairment were the most important attributes. Statistically
      significant preferences were observed for all attribute levels for time to first
      SRE, risk of renal impairment, and mode of administration. Predicted choice
      probability analysis showed that physicians preferred a hypothetical medication
      with attributes similar to those of denosumab over one with attributes similar to
      those of zoledronic acid. CONCLUSIONS: Physicians indicated that clinical
      attributes are important when considering bone-targeting therapy for bone
      metastases, but consistent with the current health care landscape, patient out-of
      pocket cost was the most important. With health care costs being increasingly
      shifted to patients, physicians require accurate information about co-pays and
      assistance programs to avoid patients receiving less costly, yet potentially
      inferior, treatment.

PMID- 25595238
TI  - Evaluation of patient registries supporting reimbursement decisions: the case of
      oxaliplatin for treatment of stage III colon cancer.
AB  - BACKGROUND: Access with evidence development has been established for expensive
      intramural drugs in The Netherlands. The procedure involves a 4-year period of
      conditional reimbursement. During this period, additional evidence has to be
      gathered usually through a patient registry. Given the costs and time involved in
      gathering the data, it is important to carefully evaluate the registry.
      OBJECTIVES: This study aimed to develop a model for the regular evaluation of
      patient registries during an access with evidence development process and find
      the optimal length of the registry period. METHODS: We used data from a recent
      registry in The Netherlands on oxaliplatin as a treatment option for stage III
      colon cancer. We added simulated follow-up data to the empirical data available
      and applied value of information analysis to balance the gains of extending the
      period and amount of data gathering against the costs of registering patients.
      RESULTS: We show that given the assumptions on cohort size, follow-up time, and
      purpose of the registry, the current (partly simulated) registry was not very
      efficient. Notably, the observation period could have been stopped to make a
      definite reimbursement decision after a maximum of 2 years rather than the fixed
      4-year period. CONCLUSIONS: Patient registries may be an efficient way to gather
      data on new medical treatments, but they need to be carefully designed and
      evaluated, in particular regarding their follow-up time. For each purpose, data
      gathering can be tailored to make sure decisions are taken at the moment that
      sufficient data are available.

PMID- 25595239
TI  - Risk attitudes and personality traits predict perceptions of benefits and risks
      for medicinal products: a field study of European medical assessors.
AB  - BACKGROUND: Risk attitudes and personality traits are known predictors of
      decision making among laypersons, but very little is known of their influence
      among experts participating in organizational decision making. METHODS: Seventy
      five European medical assessors were assessed in a field study using the Domain
      Specific Risk Taking scale and the Big Five Inventory scale. Assessors rated the
      risks and benefits for a mock "clinical dossier" specific to their area of
      expertise, and ordinal regression models were used to assess the odds of risk
      attitude or personality traits in predicting either the benefit or the risk
      ratings. RESULTS: An increase in the "conscientiousness" score predicted an
      increase in the perception of the drug's benefit, and male assessors gave higher
      scores for the drug's benefit ratings than did female assessors. Extraverted
      assessors saw fewer risks, and assessors with a perceived neutral-averse or
      averse risk profile saw greater risks. CONCLUSIONS: Medical assessors perceive
      the benefits and risks of medicines via a complex interplay of the medical
      situation, their personality traits and even their gender. Further research in
      this area is needed to determine how these potential biases are managed within
      the regulatory setting.

PMID- 25595240
TI  - Determining the impact of modeling additional sources of uncertainty in value-of
      information analysis.
AB  - BACKGROUND: The conditional reimbursement policy for expensive medicines in The
      Netherlands requires data collection on actual use and cost-effectiveness after
      the initial decision to reimburse a drug. This introduces new sources of
      uncertainty (less important in a randomized controlled trial than in daily
      practice), which may affect priorities for further research. OBJECTIVES: This
      article focuses on determining the impact of including these uncertainties at the
      time a decision is made, and whether more complex models are always needed to
      address prioritization of additional research. METHODS: We constructed a typical
      decision model for chronic progressive diseases with four health states and
      parameters related to transition and exacerbation probabilities, costs, and
      utilities. Different scenarios are built on the basis of three additional
      uncertainties: persistence, compliance, and broadening of indication. Persistence
      refers to treatment duration. Compliance describes the fraction of treatment
      benefit obtained because of not taking the medication as prescribed. Broadening
      of indication reflects a shift in the severity distribution at treatment start.
      These uncertainties were parameterized in the model and included in the value-of
      information analysis. RESULTS: The most important parameters were transition
      probabilities. Broadening of indication had little impact on the overall
      uncertainty. Compliance and persistence were important when establishing
      priorities for further research. Major differences with respect to the reference
      scenario were due to the parameterization of compliance in the decision model.
      CONCLUSIONS: The usual practice of modeling only randomized controlled trial data
      at the time the decision on conditional reimbursement is made can lead to wrong
      decisions. Additional uncertainties arising from outcomes studies should be
      anticipated at an early stage and included in the model because this can have a
      strong impact on the prioritization of further research.

PMID- 25595241
TI  - Measuring change in quality of life: bias in prospective and retrospective
      evaluation.
AB  - OBJECTIVES: Treatment effects on health-related quality of life (QOL) often
      differ depending on whether they are measured prospectively (before and after
      treatment) or retrospectively (after treatment only). These two approaches can be
      subject to different sorts of bias: Prospective evaluations may be biased by
      scale recalibration (a changed understanding of the response scale), and
      retrospective evaluations may be biased by recall bias (a wrong assessment of
      former QOL). METHODS: On the basis of an analysis of the literature, we present
      an overview on possible biases in prospective and retrospective measurement of
      QOL and how these biases are named and defined in the literature. RESULTS: The
      definitions of different biases are inconsistent. Many authors do not clearly
      distinguish measurement bias from true change. Furthermore, some consider only
      scale recalibration or only recall bias. CONCLUSIONS: Much of the current
      discussion on bias in prospective and retrospective QOL measurement suffers from
      unclear definitions, especially of "response shift" and "recall bias," or from
      neglecting one of the possible biases. We suggest more elaborate definitions for
      different types of bias and recommend taking both kinds of bias into
      consideration when measuring change in QOL. The relevance of the different biases
      depends on the type of study, and so either prospective or retrospective
      assessment may be more appropriate.

PMID- 25595242
TI  - Network meta-analysis: development of a three-level hierarchical modeling
      approach incorporating dose-related constraints.
AB  - BACKGROUND: Network meta-analysis (NMA) is commonly used in evidence synthesis;
      however, in situations in which there are a large number of treatment options,
      which may be subdivided into classes, and relatively few trials, NMAs produce
      considerable uncertainty in the estimated treatment effects, and consequently,
      identification of the most beneficial intervention remains inconclusive.
      OBJECTIVE: To develop and demonstrate the use of evidence synthesis methods to
      evaluate extensive treatment networks with a limited number of trials, making use
      of classes. METHODS: Using Bayesian Markov chain Monte Carlo methods, we build on
      the existing work of a random effects NMA to develop a three-level hierarchical
      NMA model that accounts for the exchangeability between treatments within the
      same class as well as for the residual between-study heterogeneity. We
      demonstrate the application of these methods to a continuous and binary outcome,
      using a motivating example of overactive bladder. We illustrate methods for
      incorporating ordering constraints in increasing doses, model selection, and
      assessing inconsistency between the direct and indirect evidence. RESULTS: The
      methods were applied to a data set obtained from a systematic literature review
      of trials for overactive bladder, evaluating the mean reduction in incontinence
      episodes from baseline and the number of patients reporting one or more adverse
      events. The data set involved 72 trials comparing 34 interventions that were
      categorized into nine classes of interventions, including placebo. CONCLUSIONS:
      Bayesian three-level hierarchical NMAs have the potential to increase the
      precision in the effect estimates while maintaining the interpretability of the
      individual interventions for decision making.

PMID- 25595243
TI  - Optimizing the leveraging of real-world data to improve the development and use
      of medicines.
AB  - Health research, including health outcomes and comparative effectiveness
      research, is on the cusp of a golden era of access to digitized real-world data,
      catalyzed by the adoption of electronic health records and the integration of
      clinical and biological information with other data. This era promises more
      robust insights into what works in health care. Several barriers, however, will
      need to be addressed if the full potential of these new data are fully realized;
      these will involve both policy solutions and stakeholder cooperation. Although a
      number of these issues have been widely discussed, we focus on the one we believe
      is the most important-the facilitation of greater openness among public and
      private stakeholders to collaboration, connecting information and data sharing,
      with the goal of making robust and complete data accessible to all researchers.
      In this way, we can better understand the consequences of health care delivery,
      improve the effectiveness and efficiency of health care systems, and develop
      advancements in health technologies. Early real-world data initiatives illustrate
      both potential and the need for future progress, as well as the essential role of
      collaboration and data sharing. Health policies critical to progress will include
      those that promote open source data standards, expand access to the data,
      increase data capture and connectivity, and facilitate communication of findings.

PMID- 25595244
TI  - Do the current performance-based schemes in Italy really work? "Success fee": a
      novel measure for cost-containment of drug expenditure.
AB  - BACKGROUND: Drug costs have risen rapidly in the last decade, driving third-party
      payers to adopt performance-based agreements that provide either a discount
      before payment or an ex post reimbursement on the basis of treatments'
      effectiveness and/or safety issues. OBJECTIVES: This article analyses the
      strategies currently approved in Italy and proposes a novel model called "success
      fee" to improve payment-by-result schemes and to guarantee patients rapid access
      to novel therapies. METHODS: A review of the existing risk-sharing schemes in
      Italy has been performed, and data provided by the Italian National report (2012)
      on drug use have been analyzed to assess the impact on drug expenditure deriving
      from the application of "traditional" performance-based strategies since their
      introduction in 2006. RESULTS: Such schemes have poorly contributed to the
      fulfillment of the purpose in Italy, producing a trifling refund, compared with
      relevant drugs costs for the National Health System : ?121 million out of a total
      of ?3696 million paid. The novel risk-sharing agreement called "success fee" has
      been adopted for a new high-cost therapy approved for idiopathic pulmonary
      fibrosis, pirfenidone, and consists of an ex post payment made by the National
      Health System to the manufacturer for those patients who received a real benefit
      from treatment. CONCLUSIONS: "Success fee" represents an effective strategy to
      promote value-based pricing, making available to patients a rapid access to
      innovative and expensive therapies, with an affordable impact on drug expenditure
      and, simultaneously, ensuring third-party payers to share with manufacturers the
      risk deriving from uncertain safety and effectiveness.

PMID- 25595245
TI  - The effect of simulation on skill performance: a need for change in pediatric
      nursing education.
AB  - BACKGROUND: This study sought to determine if student's performance of safety
      skills improved following a simulated educational experience. METHODS: Further
      analysis of data from a quasi-experimental design (n=73) was examined to identify
      if student's skill performance improved following a simulated educational
      intervention. RESULTS: Students did show an improvement in skill performance, but
      even after the intervention over half the students did not assess patient
      identification, over half did not administer medications safely, and students
      struggled with communicating nursing recommendations. CONCLUSION: Further
      research needs to focus on skill performance and assessing students' ability to
      provide safe nursing care.

PMID- 25595246
TI  - Characterization of a new rat model for chronic inflammatory demyelinating
      polyneuropathies.
AB  - Our objective was to develop a chronic model of EAN which could be used as a tool
      to test treatment strategies for CIDP. Lewis rats injected with S-palmitoylated
      P0(180-199) peptide developed a chronic, sometimes relapsing-remitting type of
      disease. Our model fulfills electrophysiological criteria of demyelination with
      axonal degeneration, confirmed by immunohistopathology. The late phase of the
      chronic disease was characterized by accumulation of IL-17(+) cells and
      macrophages in sciatic nerves and by high serum IL-17 levels. In conclusion, we
      have developed a reliable and reproducible animal model resembling CIDP that can
      now be used for translational drug studies. 

PMID- 25595247
TI  - Retinoic acid enhances the levels of IL-10 in TLR-stimulated B cells from
      patients with relapsing-remitting multiple sclerosis.
AB  - We have explored the beneficial effects of retinoic acid (RA) on B cells from
      multiple sclerosis (MS) patients. When co-stimulated via the toll-like receptors
      (TLRs) TLR9 and RP105, MS B cells secreted less of the anti-inflammatory cytokine
      interleukin 10 (IL-10) compared to B cells from healthy controls. Importantly, RA
      enhanced the secretion of IL-10 by MS-derived B cells without affecting the
      levels of the pro-inflammatory cytokine TNF-alpha. RA revealed the same ability
      to induce IL-10 as did interferon-beta-1b (IFN-beta-1b), and B-cells from
      patients treated with glatiramer acetate or IFN-beta-1b still displayed the
      beneficial effects of RA on the IL-10/TNF-alpha ratio. 

PMID- 25595248
TI  - Specific adsorbents for myasthenia gravis autoantibodies using mutants of the
      muscle nicotinic acetylcholine receptor extracellular domains.
AB  - Myasthenia gravis (MG) is usually caused by antibodies against the muscle
      acetylcholine receptor (AChR). Plasmapheresis and immunoadsorption are often used
      to treat non-responsive patients. Antigen-specific immunoadsorption would remove
      only the pathogenic autoantibodies reducing side-effects. We expressed AChR
      extracellular domain mutants for use as specific adsorbents, and characterized
      them. Antigenicity and capacity for autoantibody binding were improved compared
      to the wild-type proteins. Adsorption appeared to be fast, as high plasma flow
      rates could be applied. The bound autoantibodies were eluted repeatedly, allowing
      column reuse, without compromise in efficiency. Overall, the adsorbents were
      specific, efficient and suitable for use in therapy. 

PMID- 25595250
TI  - Chronic systemic IL-1beta exacerbates central neuroinflammation independently of
      the blood-brain barrier integrity.
AB  - Peripheral circulating cytokines are involved in immune to brain communication
      and systemic inflammation is considered a risk factor for flaring up the symptoms
      in most neurodegenerative diseases. We induced both central inflammatory
      demyelinating lesion, and systemic inflammation with an interleukin-1beta
      expressing adenovector. The peripheral pro-inflammatory stimulus aggravated the
      ongoing central lesion independently of the blood-brain barrier (BBB) integrity.
      This model allows studying the role of specific molecules and cells (neutrophils)
      from the innate immune system, in the relationship between central and peripheral
      communication, and on relapsing episodes of demyelinating lesions, along with the
      role of BBB integrity. 

PMID- 25595249
TI  - Quantitative analysis of aquaporin-4 antibody in longitudinally extensive
      transverse myelitis.
AB  - Aquaporin-4 (AQP-4) antibody-positive longitudinally extensive transverse
      myelitis (LETM) is referred to as a neuromyelitis optica (NMO) spectrum disorder.
      We conducted an exploratory investigation of correlations between AQP-4 antibody
      serum levels, as determined by a fluorescent immunoprecipitation assay, and
      clinical characteristics in LETM. Expanded Disability Status Scores (EDSS) scores
      and number of segments of spinal cord involved were positively correlated to AQP
      4 antibody levels. However, serum AQP-4 antibody levels were not correlated with
      the time to next attack or the conversion time of LETM to NMO, although
      seropositive LETM patients demonstrated a high conversion rate to NMO (78.1%). 

PMID- 25595251
TI  - Sepsis progression to multiple organ dysfunction in carotid chemo/baro-denervated
      rats treated with lipopolysaccharide.
AB  - Sepsis progresses to multiple organ dysfunction (MOD) due to the uncontrolled
      release of inflammatory mediators. Carotid chemo/baro-receptors could play a
      protective role during sepsis. In anesthetized male rats, we measured
      cardiorespiratory variables and plasma TNF-alpha, glucocorticoids, epinephrine,
      and MOD marker levels 90min after lipopolysaccharide (LPS) administration in
      control (SHAM surgery) and bilateral carotid chemo/baro-denervated (BCN) rats.
      BCN prior to LPS blunted the tachypneic response and enhanced tachycardia and
      hypotension. BCN-LPS rats also showed blunted plasma glucocorticoid responses,
      boosted epinephrine and TNF-alpha responses, and earlier MOD onset with a lower
      survival time compared with SHAM-LPS rats. Consequently, the complete absence of
      carotid chemo/baro-sensory function modified the neural, endocrine and
      inflammatory responses to sepsis. Thus, carotid chemo/baro-receptors play a
      protective role in sepsis. 

PMID- 25595252
TI  - A clinical and laboratory study evaluating the profile of cytokine levels in
      relapsing remitting and secondary progressive multiple sclerosis.
AB  - The main aim of the study was to evaluate levels of cytokines IL-1ra, IL-2, IL-4,
      IL-6, IL-8, IL-10, IL-12, IL-17, TNF-alfa, TGB-beta1 and IFN-gamma in 30 patients
      with relapsing remitting (RRMS) compared to 30 secondary progressive multiple
      sclerosis (SPMS) in a peripheral blood sample. Statistical analysis showed
      significant higher levels of IL-17 and INF-gamma, which are cytokines with pro
      inflammatory properties, and lower levels of TGF-beta1, a molecule with
      immunosuppressant activity, in RRMS compared to SPMS. These results underline the
      existence of a different cytokines dysregulation in RRMS compared to SPMS phases
      with higher pro-inflammatory activity in RRMS. 

PMID- 25595253
TI  - Plasmacytosis is a common immune signature in patients with MMN and CIDP and
      responds to treatment with IVIg.
AB  - B cells and antibodies are thought to be relevant in chronic immune neuropathies
      (CIN). We analysed peripheral B-cell homeostasis and effects of high-dose
      intravenous immunoglobulin (IVIg) on B-cell phenotypes in patients with
      multifocal motor neuropathy (n=22) and chronic inflammatory demyelinating
      polyneuropathy (n=8) by multi-color flow cytometry. At baseline, total B-cell
      numbers were decreased, but mature plasma cells were markedly elevated. IVIg
      rapidly prompted a decrease in plasma cell numbers and left B-cell homeostasis
      unchanged. Thus, expanded frequencies of plasma cells might be involved in CIN
      immunopathogenesis and are downscaled after clinically successful IVIg
      administration. 

PMID- 25595254
TI  - Plasma levels of alarmin IL-33 are unchanged in autism spectrum disorder: a
      preliminary study.
AB  - The pathogenesis of autism spectrum disorder (ASD) is unknown, and the immune
      system has been appointed to play an important role. The interleukin 33 (IL-33),
      a member of the IL-1, may act as an alarmin. This study aimed to evaluate plasma
      levels of IL-33, sST2, and IL-1beta in 30 patients with ASD in comparison with 18
      controls matched by gender, age and maternal age at childbirth. Patients did not
      differ from controls in IL-33, sST2, and IL-1beta plasma levels. Alarmin levels
      were not correlated with age, and neither was influenced by clinical parameters.
      Our results undermine the role of IL-33/ST2 in ASD. 

PMID- 25595255
TI  - B cell recognition of myelin oligodendrocyte glycoprotein autoantigen depends on
      immunization with protein rather than short peptide, while B cell invasion of the
      CNS in autoimmunity does not.
AB  - We develop a new fusion protein reagent (MOGtag), based on the extracellular
      domain of mouse myelin oligodendrocyte glycoprotein (MOG1-125), designed to
      induce autoimmune responses in mice that incorporates both T and B cell
      recognition of antigen. Reports of similar reagents, primarily based on foreign
      MOG proteins, rely largely on disease incidence and severity, with little
      analysis of the underlying immune response or pathology. We characterize the
      immune response and central nervous system autoimmune disease elicited by MOGtag
      in mice and find that it results in the formation of a T cell-dependent germinal
      center B cell response. Unlike immunization with the short MOG35-55 peptide, this
      response incorporated B cells able to recognize MOG protein. The autoimmune
      disease resulting from immunization with MOGtag was chronic with clear evidence
      of an ongoing immune response and active white and gray matter infiltration by T
      cells as well as formation of B cell clusters in the meninges. Interestingly,
      development of B cell clusters was not absolutely dependent on the ability of B
      cells to recognize MOG protein, as they were also present in mice immunized with
      short peptide and in mice with a mutant B cell receptor specific for an
      irrelevant antigen. 

PMID- 25595256
TI  - Dysregulated production of leukemia inhibitory factor in immune cells of
      relapsing remitting multiple sclerosis patients.
AB  - Leukemia inhibitory factor (LIF) is known to potentiate the differentiation and
      survival of neuronal and oligodendrocyte precursors. Systemic therapy with LIF
      reportedly ameliorated the severity of experimental autoimmune encephalomyelitis
      and prevented oligodendrocyte death. We studied the secreted LIF levels from
      immune cells of relapsing remitting multiple sclerosis (RR-MS) patients compared
      to age- and gender-matched healthy controls (HCs). LIF was barely detected in the
      supernatants when the cells were not stimulated. After stimulation with anti
      CD3/CD28 monoclonal antibody, LIF levels were up-regulated in both patients and
      controls, although to a significantly lower extent in RR-MS patients compared to
      HC. There were no significant differences between untreated patients and
      interferon-beta1a treated patients. This is a heretofore unreported aspect of
      immune dysregulation in patients with RR-MS that may be related to insufficient
      remyelination and neurogenesis in MS lesions. 

PMID- 25595257
TI  - Co-stimulation with TNF receptor superfamily 4/25 antibodies enhances in-vivo
      expansion of CD4+CD25+Foxp3+ T cells (Tregs) in a mouse study for active DNA
      Abeta42 immunotherapy.
AB  - The study was designed to test DNA Abeta42 immunization in mice as alternative
      approach for possible active immunotherapy in Alzheimer patients. As results, we
      found polarized Th2 immune responses, efficient Abeta42 antibody levels, and
      disappearance of antigen specific T cells. In-vivo TNFRSF4/25 antibody co
      stimulation enhanced Abeta42 specific T cell responses with initial Th2 expansion
      and subsequent development of Abeta42 specific CD4+CD25+Foxp3+ cells. It showed
      that Th2 biased responses due to gene gun immunizations propagate the development
      of regulatory T cells. In conclusion, full-length DNA Abeta42 immunization into
      skin results in a regulatory response with minimal risk of inflammation and
      autoimmunity. 

PMID- 25595259
TI  - Dermatomyositis as a presentation of neuromyelitis optica spectrum disorder.
AB  - IMPORTANCE: This is the first report of neuromyelitis optica spectrum disorder
      (NMOSD) associated with dermatomyositis (DM). REPORT: A 40year-old Caucasian
      female presented with 6months of worsening fatigue, rash, acute weakness worse in
      her lower extremities, and urinary retention. She was found to have both NMOSD
      and anti-melanoma differentiation-associated gene (MDA)5 positive DM with
      interstitial lung disease (ILD). She was treated aggressively and she regained
      her ability to ambulate. CONCLUSION: We recommend considering NMOSD in the
      differential diagnosis of patients with DM and other autoimmune disorders that
      also present with clinical signs of myelopathy.

PMID- 25595258
TI  - Central mediators involved in the febrile response induced by polyinosinic
      polycytidylic acid: lack of involvement of endothelins and substance P.
AB  - The present study evaluated the involvement of interleukin(IL)-1beta, tumor
      necrosis factor-alpha (TNF-alpha), IL-6, interferon(IFN)-gamma, prostaglandins of
      the E2 series, endothelins, substance P and opioids within the central nervous
      system in polyinosinic:polycytidylic acid (Poly I:C)-induced fever in rats. Poly
      I:C injection induced a febrile response which was reduced by
      intracerebroventricular administration of the antibodies against TNF-alpha, IL-6,
      or IFN-gamma, or by IL-1 or MU receptor antagonists. Intraperitoneal injection of
      indomethacin or oral administration of celecoxib also reduced Poly I:C-induced
      fever. Poly I:C increased prostaglandin E2 levels in the cerebrospinal fluid of
      the animals which was also reduced by indomethacin. The intracerebroventricular
      injection of ETB or NK1 receptor antagonists did not alter Poly I:C-induced
      fever. These data suggest the involvement of IL-1beta, TNF-alpha, IL-6, IFN
      gamma, prostaglandin E2, and opioids but not endothelins and substance P on Poly
      I:C-induced fever. 

PMID- 25595260
TI  - Dynamic changes in meningeal inflammation correspond to clinical exacerbations in
      a murine model of relapsing-remitting multiple sclerosis.
AB  - Inflammation in the meninges, tissues surrounding the brain and spinal cord that
      enclose the cerebrospinal fluid, closely parallels clinical exacerbations in
      relapsing-remitting experimental autoimmune encephalomyelitis (EAE). In
      preclinical disease, an influx of innate immune cells precedes loss of blood
      brain barrier (BBB) integrity and large-scale inflammation in the central nervous
      system (CNS). T cell infiltration into the meninges is observed in acute disease
      as well as during relapse, when neither BBB permeability nor significant
      increases in peripherally-derived immune cell numbers in the CNS are observed.
      These findings support the idea that the meninges are a gateway for immune cell
      access into the CNS, a finding that has important therapeutic implications. 

PMID- 25595261
TI  - Age-related changes in spleen of Dark Agouti rats immunized for experimental
      autoimmune encephalomyelitis.
AB  - The study was undertaken considering age-related changes in susceptibility to
      experimental autoimmune encephalomyelitis (EAE) and a putative role of spleen in
      pathogenesis of this disease. The phenotypic and functional characteristics of T
      splenocytes were examined in young (3-month-old), middle-aged (8-month-old) and
      aged (26-month-old) Dark Agouti rats immunized for EAE with rat spinal cord in
      complete Freund's adjuvant. The rat susceptibility to EAE induction, as well as
      the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords
      progressively decreased with aging. To the contrary, in rats immunized for EAE
      the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3- and
      CD4+CD40L+ cells, progressively increased with aging. This was associated with
      age-related increase in (i) CD4+ splenocyte surface expression of CD44, the
      molecule suggested to be involved in limiting emigration of encephalitogenic CD4+
      cells from spleen into blood and (ii) frequency of regulatory T cells, including
      CD4+CD25+FoxP3+ cells, which are also shown to control encephalitogenic cell
      migration from spleen into the central nervous system. In favor of expansion of T
      regulatory cell pool in aged rats was the greater concentration of IL-10 in
      unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated
      splenocyte cultures from aged rats compared with the corresponding cultures from
      young ones. Consistent with the age-related increase in the expression of CD44,
      which is shown to favor Th1 effector cell survival by interfering with CD95
      mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes,
      despite the greater frequency of CD95+ cells, was diminished in splenocyte
      cultures from aged compared with young rats. In addition, in control, as well as
      in ConA- and MBP-stimulated splenocyte cultures from aged rats, despite of
      impaired CD4+ cell proliferation, IFN-gamma concentrations were greater than in
      corresponding cultures from young rats. This most likely reflected increased
      abundance of IFN-gamma-producing cells in splenocyte cultures from aged compared
      with young rats. The diminished CD4+ cell proliferation in response to ConA and
      MBP in splenocyte cultures from aged compared with young rats could be, at least
      partly, associated with an enhanced splenic expression of iNOS mRNA in aged rats.
      Thus, the study suggests that age-associated changes leading to entrapping of
      activated CD4+ cells in the spleen could contribute to the restriction in
      development of EAE in aged rats. 

PMID- 25595262
TI  - Evaluation of pentraxin-3 in POEMS syndrome.

PMID- 25595263
TI  - Contribution of TIMP4 rs3755724 polymorphism to susceptibility to focal epilepsy
      in Malaysian Chinese.
AB  - Neuroinflammation can damage the brain and plays a critical role in the
      pathophysiology of epilepsy. Tissue inhibitor of metalloproteinase 4 (TIMP4) is
      an inflammation-induced apoptosis and matrix turnover factor involved in several
      neuronal disorders and inflammatory diseases. Evidence has shown linkage
      disequilibrium between rs3755724 (-55C/T) of this gene with synapsin 2 (SYN2)
      rs3773364 and peroxisome proliferator-activated G receptor (PPARG) rs2920502
      loci, which contribute to epilepsy in Caucasians. The aim of this study was to
      examine the association of these loci alone or their haplotypes with the risk of
      epilepsy in the Malaysian population. Genomic DNA of 1241 Malaysian Chinese,
      Indian, and Malay subjects (670 patients with epilepsy and 571 healthy
      individuals) was genotyped for the candidate loci by using the Sequenom MassArray
      method. Allele and genotype association of rs3755724 with susceptibility to
      epilepsy was significant in the Malaysian Chinese with focal epilepsy under
      codominant and dominant models (C vs. T: 1.5 (1.1-2.0), p=0.02; CT vs. TT: 1.8
      (1.2-2.8), p=0.007 and 1.8 (1.2-2.7), p=0.006, respectively). The T allele and
      the TT genotype were more common in patients than in controls. No significant
      association was found between rs2920502 and rs3773364-rs3755724-rs2920502
      haplotypes for susceptibility to epilepsy in each ethnicity. This study provides
      evidence that the promoter TIMP4 rs3755724 is a new focal epilepsy susceptibility
      variant that is plausibly involved in inflammation-induced seizures in Malaysian
      Chinese. 

PMID- 25595264
TI  - Astrocytic TLR4 expression and LPS-induced nuclear translocation of STAT3 in the
      sensory circumventricular organs of adult mouse brain.
AB  - The sensory circumventricular organs (CVOs) comprise the organum vasculosum of
      the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP) and
      lack the blood-brain barrier. The expression of Toll-like receptor 4 (TLR4) was
      seen at astrocytes throughout the sensory CVOs and at microglia in the AP and
      solitary nucleus around the central canal. The peripheral and central
      administration of lipopolysaccharide induced a similar pattern of nuclear
      translocation of STAT3. A microglia inhibitor minocycline largely suppressed
      lipopolysaccharide-induced astrocytic nuclear translocation of STAT3 in the OVLT
      and AP, but its effect was less in the SFO. 

PMID- 25595265
TI  - Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial
      prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.
AB  - Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid
      type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate
      ECB effects is associated with increase in AEA levels in several encephalic
      areas, including the prefrontal cortex (PFC). Activation of CB1 receptors by CB1
      agonists injected directly into these areas is usually anxiolytic. However,
      depending on the encephalic region being investigated and on the stressful
      experiences, opposite effects were observed, as reported in the ventral HIP. In
      addition, contradictory results have been reported after CB1 activation in the
      dorsal HIP (dHIP). Therefore, in the present paper we have attempted to verify if
      directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion
      of the medial PFC (MPFC) and dHIP would produce different effects in two
      conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel
      conflict test (VCT). We observed that drugs which interfere with ECB
      reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced
      anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors,
      suggesting that CB1 signaling in these brain regions modulates defensive
      responses to both innate and learned threatening stimuli. This data further
      strengthens previous results indicating modulation of hippocampal and MPFC
      activity via CB1 by ECBs, which could be therapeutically targeted to treat
      anxiety disorders. 

PMID- 25595266
TI  - Large-scale serological survey of bovine ephemeral fever in China.
AB  - Bovine ephemeral fever (BEF) is caused by the arthropod-borne bovine ephemeral
      fever virus (BEFV), which is classified in the family Rhabdoviridae and the genus
      Ephemerovirus. A debilitating and sometimes fatal viral disease, BEF affects
      cattle and water buffalo. The epizootiology of BEF among cattle in China has not
      been fully determined. We examined the seroprevalence of the BEFV among cattle in
      China between January 2012 and June 2014. Among the 2822 serum samples collected
      from various cattle breeds in 26 provinces in China, the seropositive rate for
      the BEFV ranged from 0% to 81% between regions and species. Our findings show
      that BEFV was prevalent in the all of the regions tested in our study and provide
      the first reliable reference regarding BEF surveillance in China. 

PMID- 25595267
TI  - Contrasting clinical outcomes in two cohorts of cats naturally infected with
      feline immunodeficiency virus (FIV).
AB  - Despite over 25 years of feline immunodeficiency virus (FIV) research, relatively
      little is known about the longitudinal course of FIV infection following natural
      infection. In contrast to published reports of experimental infections using
      lethal strains of the virus, clinical signs of naturally acquired FIV infection
      can be mild or inapparent, rather than life-threatening. In this prospective,
      longitudinal controlled study, based in Chicago, IL (n=17) and Memphis, TN
      (n=27), we investigated two cohorts of privately owned, naturally infected cats
      kept under different housing conditions. Cats in the Chicago cohort (Group 1)
      were kept in households of <=2 cats, while the Memphis cohort (Group 2) comprised
      part of a large multi-cat household of over 60 cats kept indoors only, with
      unrestricted access to one another. The majority of cats from Group 1 did not
      display clinical signs consistent with immunodeficiency during the 22-month
      observation period. In contrast, the outcome of infection in Group 2 was
      dramatically different; 17/27 (63%) of cats lost a median of 51.3% of their
      bodyweight (P<0.0005) and died during the study period, with lymphoma being the
      most common cause of mortality. Although the decrease in CD4+ T cell count
      between enrolment and terminal disease was significant (P=0.0017), the CD4:CD8
      ratio at the time of enrolment did not reliably distinguish FIV-positive cats
      classified as 'healthy' and 'not healthy' at either cohort. FIV load at enrolment
      was significantly lower in Group 1 than in Group 2 (P<0.0001), but there were no
      significant differences at enrolment between healthy and not healthy cats at
      either group. In conclusion, the results of this study suggest that management
      and housing conditions impact on disease progression and survival times of FIV
      positive cats. 

PMID- 25595269
TI  - Safely completed therapeutic hypothermia in postpartum cardiac arrest survivors.
AB  - Recently, therapeutic hypothermia (TH) has been used as one of the most important
      treatments for post-cardiac arrest care. Although TH induces several
      complications, it is performed across various medical fields. The following
      series of case studies describes 2 cases of postpartum cardiac arrest, treated
      with TH without serious complications. Although 1 patient exhibited coagulopathy
      and bleeding tendencies, this report suggests further application for TH.
      Therefore, emergency physicians should consider TH for the treatment of
      postpartum cardiac arrest.

PMID- 25595270
TI  - Real-time optic nerve sheath diameter reduction measured with bedside ultrasound
      after therapeutic lumbar puncture in a patient with idiopathic intracranial
      hypertension.
AB  - Idiopathic intracranial hypertension (IIH), also referred to as pseudotumor
      cerebri, is a condition of raised intracranial pressure (ICP) with unknown
      etiology. Sonographic measurement of optic nerve sheath diameter (ONSD) has been
      shown to be a reliable, noninvasive method to characterize elevated ICP in a
      variety of settings. However, little is known about the immediate response of
      ONSD to an acute reduction in ICP after lumbar puncture. We describe a case of an
      emergency department patient with IIH in whom we identified real-time change in
      ONSD correlated with a decrease in cerebrospinal fluid pressure after a
      therapeutic lumbar puncture. Ocular ultrasound and ONSD measurements were
      performed by a trained provider using a 9- to 13-MHz linear transducer and an
      ultrasound machine with ocular software package and low mechanical index settings
      for data collection (MTurbo; SonoSite Inc, Bothell, WA). The ONSD was measured 30
      minutes prior to and 30 minutes after a therapeutic lumbar puncture. Opening and
      closing pressures were recorded. Optic nerve sheath diameter measurements
      correlated with ICP as measured by opening and closing lumbar puncture pressures
      and showed an acute reduction in ONSD within 30 minutes after lumbar puncture.
      Sonographic measurement of ONSD reduction may be a novel, noninvasive and
      convenient way to follow acute reductions in ICP. Further investigation is
      necessary in order to validate this finding.

PMID- 25595268
TI  - Multicenter experience in hematopoietic stem cell transplantation for serious
      complications of common variable immunodeficiency.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is usually well controlled
      with immunoglobulin substitution and immunomodulatory drugs. A subgroup of
      patients has a complicated disease course with high mortality. For these
      patients, investigation of more invasive, potentially curative treatments, such
      as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.
      OBJECTIVE: We sought to define the outcomes of HSCT for patients with CVID.
      METHODS: Retrospective data were collected from 14 centers worldwide on patients
      with CVID receiving HSCT between 1993 and 2012. RESULTS: Twenty-five patients
      with CVID, which was defined according to international criteria, aged 8 to 50
      years at the time of transplantation were included in the study. The indication
      for HSCT was immunologic dysregulation in the majority of patients. The overall
      survival rate was 48%, and the survival rate for patients undergoing
      transplantation for lymphoma was 83%. The major causes of death were treatment
      refractory graft-versus-host disease accompanied by poor immune reconstitution
      and infectious complications. Immunoglobulin substitution was stopped in 50% of
      surviving patients. In 92% of surviving patients, the condition constituting the
      indication for HSCT resolved. CONCLUSION: This multicenter study demonstrated
      that HSCT in patients with CVID was beneficial in most surviving patients;
      however, there was a high mortality associated with the procedure. Therefore this
      therapeutic approach should only be considered in carefully selected patients in
      whom there has been extensive characterization of the immunologic and/or genetic
      defect underlying the CVID diagnosis. Criteria for patient selection, refinement
      of the transplantation protocol, and timing are needed for an improved outcome.

PMID- 25595271
TI  - Traumatic pneumorrhachis: 2 cases and review of the literature.
AB  - The presence of air in the spinal canal is known as pneumorrhachis (PNR),
      aerorachia, intraspinal pneumocele, pneumosaccus, pneumomyelogra, or intraspinal
      air. Pneumorrhachis may be iatrogenic, traumatic, and nontraumatic. We treated 2
      patients who had posttraumatic PNR in the cervical spine region after stab
      injuries. Case 1 was a 31-year-old man who was stabbed in the C5 to C6 region. He
      had muscle weakness (3/5) and numbness on the right side of the body. Brain
      computed tomographic (CT) scan showed pneumocephalus, and cervical CT scan showed
      PNR at the C6 level. Treatment included observation, and symptoms and weakness
      improved within 7 days. Case 2 was a 40-year-old man who was stabbed in the C3 to
      C4 region. He had muscle weakness (1/5) and numbness on the left side of the
      body. Brain CT scan showed pneumocephalus, and cervical CT scan showed PNR at the
      C3 level. Cerebrospinal fluid drainage persisted, and he was treated with
      surgical repair of a dural laceration. Muscle strength improved. In summary, PNR
      is a rare condition that usually is treated nonoperatively. However, surgical
      treatment may be indicated for persistent neurologic symptoms or signs; the air
      detected in the spinal canal with radiographic imaging may be associated with an
      active cerebrospinal fluid leak and may cause spinal compression.

PMID- 25595272
TI  - The accuracy of sonographic confirmation of intraosseous line placement vs
      physical examination and syringe aspiration.

PMID- 25595274
TI  - Endometrial stromal tumours revisited: an update based on the 2014 WHO
      classification.
AB  - Endometrial stromal tumours (EST) are rare tumours of endometrial stromal origin
      that account for less than 2% of all uterine tumours. Recent cytogenetic and
      molecular advances in this area have improved our understanding of ESTs and
      helped refine their classification into more meaningful categories. Accordingly,
      the newly released 2014 WHO classification system recognises four categories:
      endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS),
      high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine
      sarcoma (UUS). At the molecular level, these tumours may demonstrate a relatively
      simple karyotype with a defining chromosomal rearrangement (as in the majority of
      ESNs, LGESSs and YWHAE-rearranged HGESS) or demonstrate complex cytogenetic
      aberrations lacking specific rearrangements (as in UUSs). Herein we provide an
      update on this topic aimed at the practicing pathologist. 

PMID- 25595273
TI  - Perception of differences in naturalistic dynamic scenes, and a V1-based model.
AB  - We investigate whether a computational model of V1 can predict how observers rate
      perceptual differences between paired movie clips of natural scenes. Observers
      viewed 198 pairs of movies clips, rating how different the two clips appeared to
      them on a magnitude scale. Sixty-six of the movie pairs were naturalistic and
      those remaining were low-pass or high-pass spatially filtered versions of those
      originals. We examined three ways of comparing a movie pair. The Spatial Model
      compared corresponding frames between each movie pairwise, combining those
      differences using Minkowski summation. The Temporal Model compared successive
      frames within each movie, summed those differences for each movie, and then
      compared the overall differences between the paired movies. The Ordered-Temporal
      Model combined elements from both models, and yielded the single strongest
      predictions of observers' ratings. We modeled naturalistic sustained and
      transient impulse functions and compared frames directly with no temporal
      filtering. Overall, modeling naturalistic temporal filtering improved the models'
      performance; in particular, the predictions of the ratings for low-pass spatially
      filtered movies were much improved by employing a transient impulse function. The
      correlations between model predictions and observers' ratings rose from 0.507
      without temporal filtering to 0.759 (p = 0.01%) when realistic impulses were
      included. The sustained impulse function and the Spatial Model carried more
      weight in ratings for normal and high-pass movies, whereas the transient impulse
      function with the Ordered-Temporal Model was most important for spatially low
      pass movies. This is consistent with models in which high spatial frequency
      channels with sustained responses primarily code for spatial details in movies,
      while low spatial frequency channels with transient responses code for dynamic
      events. 

PMID- 25595275
TI  - Expression of proliferation markers Ki67, cyclin A, geminin and aurora-kinase A
      in primary breast carcinomas and corresponding distant metastases.
AB  - AIMS: To assess the expression of the following cell cycle regulatory proteins in
      primary metastatic breast carcinomas (MBCs) and on availability in matched
      distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA);
      and to compare the expression of these markers in early MBC (EMBC) and late MBC
      separated into groups according to median time point on metastatic event occurred
      (28 months). METHODS: The expression of the above mentioned markers was analysed
      in a total of 47 primary MBCs and 59 DMs (out of which 37 were pairs) by
      immunohistochemistry. Fourteen breast carcinomas with no relapse over a 10-year
      follow-up period were utilised as control cases (CBC). RESULTS: Among the MBCs,
      22 metastasised to the bone, 4 to the lung and 21 to the central nervous system
      (CNS). Geminin (p<0.001) and Ki67 (p=0.001) were increased in the MBCs while
      aurkA and cyclin A showed no difference when compared with CBCs. There were no
      differences between aurkA, cyclin A and geminin expression in MBCs and DMs in
      general. Expression of Ki67 was, however, elevated (p=0.027) in DMs. In CNS
      metastases all markers showed elevated expression as compared to MBCs. In bone
      metastases, geminin was lower (p<0.001) compared with primary MBCs. In the
      metastases of the lung, the evaluated markers did not show different expression.
      According to the median follow-up until the metastatic event, Ki67 was found to
      be significantly elevated in EMBC (p=0.018). CONCLUSIONS: Ki67 index and geminin
      distinguish a fraction of MBC with worse prognosis, showing increased levels in
      the latter in comparison to CBC being tumour-free over a 10-year follow-up
      period. Ki67 could possibly identify a group of MBCs that develop early DMs.

PMID- 25595276
TI  - A registry-based study of thyroid paraganglioma: histological and genetic
      characteristics.
AB  - The precise diagnosis of thyroid neoplasias will guide surgical management.
      Primary thyroid paraganglioma has been rarely reported. Data on prevalence,
      immunohistochemistry (IHC), and molecular genetics in a systematic series of such
      patients are pending. We performed a multinational population-based study on
      thyroid paraganglioma and analyzed prevalence, IHC, and molecular genetics.
      Patients with thyroid paraganglioma were recruited from the European-American
      Head-and-Neck-Paraganglioma-Registry. Demographic and clinical data were
      registered. Histopathology and IHC were re-investigated. All patients with
      thyroid paraganglioma underwent molecular genetic analyses of the SDHA, SDHB,
      SDHC, SDHD, SDHAF2, VHL, RET, TMEM127, and MAX genes. Analyses included Sanger
      sequencing and multiplex ligation-dependent probe amplification (MLPA) for
      detection of large rearrangements. Of 947 registrants, eight candidates were
      initially identified. After immunohistochemical analyses of these eight subjects,
      5 (0.5%) were confirmed to have thyroid paraganglioma. IHC was positive for
      chromogranin, synaptophysin, and S-100 and negative for calcitonin in all five
      thyroid paragangliomas, whereas the three excluded candidate tumors stained
      positive for pan-cytokeratin, a marker excluding endocrine tumors. Germline
      variants, probably representing mutations, were found in four of the five
      confirmed thyroid paraganglioma cases, two each in SDHA and SDHB, whereas the
      excluded cases had no mutations in the tested genes. Thyroid paraganglioma is a
      finite entity, which must be differentiated from medullary thyroid carcinoma,
      because medical, surgical, and genetic management for each is different. Notably,
      approximately 80% of thyroid paragangliomas are associated with germline
      variants, with implications for additional tumors and a potential risk for the
      family. As opposed to sporadic tumors, surgical management and extent of
      resection are different for heritable tumors, each guided by the precise gene
      involved. 

PMID- 25595277
TI  - Symptom severity, social supports, coping styles, and quality of life among
      individuals' diagnosed with Meniere's disease.
AB  - OBJECTIVES: To (1) examine the quality of life of individuals with Meniere's
      disease in relation to symptom severity, social supports, and coping styles and
      (2) develop a prediction model to identify factors most strongly associated with
      quality of life. METHODS: Data were collected using a web-based survey that
      included previously developed and validated measures (i.e. SF-12, Dizziness
      Handicap Inventory, Hearing Handicap Inventory for Elderly Screening Version,
      Iowa Tinnitus Handicap Questionnaire, Interpersonal Support Evaluation List,
      Brief COPES, Lehman's Quality of Life). Ninety-five individuals with Meniere's
      disease who were members of one of five online Meniere's disease support groups
      responded to the survey. RESULTS: The findings indicated that symptom severity
      was negatively associated with patients' quality of life, social supports were
      positively associated with quality of life, and the use of negative coping styles
      (e.g. substance use, blaming) was negatively associated with quality of life.
      Four predictors (i.e. SF-12 mental health, dizziness severity, self-esteem
      support, and negative coping styles) accounted for 62% of the variance in quality
      of life. DISCUSSION: The findings suggest that the factors associated with the
      quality of life of patients with Meniere's disease are similar to those reported
      in the literature among patients with other chronic illnesses. The results also
      suggested that emphasis on psychosocial factors may be an important aspect of a
      comprehensive treatment intervention for individuals with Meniere's disease.

PMID- 25595278
TI  - Monitoring interactions and dynamics of endogenous beta-catenin with
      intracellular nanobodies in living cells.
AB  - beta-catenin is the key component of the canonical Wnt pathway and plays a
      crucial role in a multitude of developmental and homeostatic processes. The
      different tasks of beta-catenin are orchestrated by its subcellular localization
      and participation in multiprotein complexes. To gain a better understanding of
      beta-catenin's role in living cells we have generated a new set of single domain
      antibodies, referred to as nanobodies, derived from heavy chain antibodies of
      camelids. We selected nanobodies recognizing the N-terminal, core or C-terminal
      domain of beta-catenin and applied these new high-affinity binders as capture
      molecules in sandwich immunoassays and co-immunoprecipitations of endogenous beta
      catenin complexes. In addition, we engineered intracellularly functional anti
      beta-catenin chromobodies by combining the binding moieties of the nanobodies
      with fluorescent proteins. For the first time, we were able to visualize the
      subcellular localization and nuclear translocation of endogenous beta-catenin in
      living cells using these chromobodies. Moreover, the chromobody signal allowed us
      to trace the accumulation of diffusible, hypo-phosphorylated beta-catenin in
      response to compound treatment in real time using High Content Imaging. The anti
      beta-catenin nanobodies and chromobodies characterized in this study are
      versatile tools that enable a novel and unique approach to monitor the dynamics
      of subcellular beta-catenin in biochemical and cell biological assays. 

PMID- 25595280
TI  - Evaluation of a pilot hypertension management programme for Guatemalan adults.
AB  - Corazon Sano y Feliz is a hypertension management intervention developed to
      address deficiencies in the management of hypertensive patients in Guatemala.
      From 2007 to 2009, Corazon Sano y Feliz was pilot-tested in the community of
      Mixco. Corazon Sano y Feliz comprises a clinical risk assessment and treatment
      component implemented primarily by nurses, and a health education component
      implemented by community health workers. To accomplish our secondary objective of
      determining Corazon Sano y Feliz's potential for change at the patient level, we
      implemented a one-group pretest-posttest study design to examine changes in
      clinical measures, knowledge and practices between baseline and the end of the 6
      month intervention. Two nurses and one physician set up a hypertension clinic to
      manage patients according to risk level. Twenty-nine community health workers
      were trained in CVD risk reduction and health promotion and in turn led six
      educational sessions for patients. Comparing baseline and 6-month measures, the
      intervention achieved significant improvements in mean knowledge and behaviour
      (increase from 54.6 to 59.1 out of a possible 70 points) and significant
      reductions of mean systolic and diastolic blood pressure (27.2 and 7.7 mmHg),
      body mass index (from 26.5 to 26.2 kg/m(2)) and waist circumference (89.6-88.9
      cm). In this pilot study we obtained preliminary evidence that this community
      oriented hypertension management and health promotion intervention model was
      feasible and achieved significant reduction in risk factors. If scaled up, this
      intervention has the potential to substantially reduce CVD burden. 

PMID- 25595281
TI  - Treatment without consent?

PMID- 25595282
TI  - Bisphosphonates: game changers?

PMID- 25595283
TI  - The role of bisphosphonates in early- and advanced-stage breast cancer: have we
      finally optimized care?
AB  - Bisphosphonates have played an important role in the treatment of breast cancer,
      mainly in patients with bone metastasis, by reducing the risk of fracture, spinal
      cord compression, and hypercalcemia. Both oral and intravenous products are
      available and have strong supporting clinical evidence. Zoledronic acid, the most
      frequently used intravenous agent, has traditionally been given on a monthly
      dosing schedule. A novel every-12-weeks maintenance dosing schedule shows
      clinical equivalence and promises to improve safety, affordability, and quality
      of care. The Early Breast Cancer Trialists' Collaborative Group has recently
      helped clarify the controversial benefit of bisphosphonates in the adjuvant
      setting. Based on their meta-analysis, we now have strong evidence supporting the
      use of adjuvant bisphosphonates to help prevent the development of bone
      metastasis in postmenopausal breast cancer patients, which leads to a significant
      improvement in breast cancer-specific survival. We eagerly await the full
      publication of this practice-changing study, which continues the incremental
      advance of the treatment of patients with breast cancer. 

PMID- 25595279
TI  - Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer.
AB  - PURPOSE: Zoledronic acid is being increasingly recognized for its antitumor
      properties, but the underlying functions are not well understood. In this study,
      we hypothesized that zoledronic acid inhibits ovarian cancer angiogenesis
      preventing Rac1 activation. EXPERIMENTAL DESIGN: The biologic effects of
      zoledronic acid were examined using a series of in vitro [cell invasion, cytokine
      production, Rac1 activation, reverse-phase protein array, and in vivo (orthotopic
      mouse models)] experiments. RESULTS: There was significant inhibition of ovarian
      cancer (HeyA8-MDR and OVCAR-5) cell invasion as well as reduced production of
      proangiogenic cytokines in response to zoledronic acid treatment. Furthermore,
      zoledronic acid inactivated Rac1 and decreased the levels of Pak1/p38/matrix
      metalloproteinase-2 in ovarian cancer cells. In vivo, zoledronic acid reduced
      tumor growth, angiogenesis, and cell proliferation and inactivated Rac1 in both
      HeyA8-MDR and OVCAR-5 models. These in vivo antitumor effects were enhanced in
      both models when zoledronic acid was combined with nab-paclitaxel. CONCLUSIONS:
      Zoledronic acid has robust antitumor and antiangiogenic activity and merits
      further clinical development as ovarian cancer treatment.

PMID- 25595284
TI  - Bisphosphonates in breast cancer: a triple winner?

PMID- 25595285
TI  - Osteoclast inhibitors: a multifaceted tool in the management of breast cancer.

PMID- 25595286
TI  - Application of In-Syringe Dispersive Liquid-Liquid Microextraction and Narrow
      Bore Tube Dispersive Liquid-Liquid Microextraction for the Determination of Trace
      Amounts of BTEX in Water Samples.
AB  - Two new simple and effective methods based on dispersive liquid-liquid
      microextraction (DLLME) procedure, termed "in-syringe DLLME (IS-DLLME)" and
      "narrow-bore tube DLLME (NB-DLLME)", were developed and applied for rapid and
      simultaneous separation and preconcentration of trace amounts of benzene,
      toluene, ethylbenzene and xylene isomers in water samples followed by gas
      chromatographic analysis. Different parameters influencing the extraction
      efficiency of both methods such as type and volume of the extraction solvent and
      the disperser solvent; pH, temperature and volume of sample solution and ionic
      strength of samples were investigated and optimized. Under optimal condition, the
      limits of detection ranged from 1.7 to 2.4 ug L(-1) for IS-DLLME and 1.5 to 2.2
      ug L(-1) for NB-DLLME. Precision (as relative standard deviation) of the two
      techniques was between 2.1 and 4.6% for IS-DLLME and between 1.5 and 4.5% for NB
      DLLME. The enrichment factors found to be between 20-29 and 31-73 for IS- and NB
      DLLME, respectively. The applicability of the proposed methods was investigated
      by analyzing real water samples. 

PMID- 25595287
TI  - Integrating funds for health and social care: an evidence review.
AB  - OBJECTIVES: Integrated funds for health and social care are one possible way of
      improving care for people with complex care requirements. If integrated funds
      facilitate coordinated care, this could support improvements in patient
      experience, and health and social care outcomes, reduce avoidable hospital
      admissions and delayed discharges, and so reduce costs. In this article, we
      examine whether this potential has been realized in practice. METHODS: We propose
      a framework based on agency theory for understanding the role that integrated
      funding can play in promoting coordinated care, and review the evidence to see
      whether the expected effects are realized in practice. We searched eight
      electronic databases and relevant websites, and checked reference lists of
      reviews and empirical studies. We extracted data on the types of funding
      integration used by schemes, their benefits and costs (including unintended
      effects), and the barriers to implementation. We interpreted our findings with
      reference to our framework. RESULTS: The review included 38 schemes from eight
      countries. Most of the randomized evidence came from Australia, with
      nonrandomized comparative evidence available from Australia, Canada, England,
      Sweden and the US. None of the comparative evidence isolated the effect of
      integrated funding; instead, studies assessed the effects of 'integrated
      financing plus integrated care' (i.e. 'integration') relative to usual care. Most
      schemes (24/38) assessed health outcomes, of which over half found no significant
      impact on health. The impact of integration on secondary care costs or use was
      assessed in 34 schemes. In 11 schemes, integration had no significant effect on
      secondary care costs or utilisation. Only three schemes reported significantly
      lower secondary care use compared with usual care. In the remaining 19 schemes,
      the evidence was mixed or unclear. Some schemes achieved short-term reductions in
      delayed discharges, but there was anecdotal evidence of unintended consequences
      such as premature hospital discharge and heightened risk of readmission. No
      scheme achieved a sustained reduction in hospital use. The primary barrier was
      the difficulty of implementing financial integration, despite the existence of
      statutory and regulatory support. Even where funds were successfully pooled,
      budget holders' control over access to services remained limited. Barriers in the
      form of differences in performance frameworks, priorities and governance were
      prominent amongst the UK schemes, whereas difficulties in linking different
      information systems were more widespread. Despite these barriers, many schemes -
      including those that failed to improve health or reduce costs - reported that
      access to care had improved. Some of these schemes revealed substantial levels of
      unmet need and so total costs increased. CONCLUSIONS: It is often assumed in
      policy that integrating funding will promote integrated care, and lead to better
      health outcomes and lower costs. Both our agency theory-based framework and the
      evidence indicate that the link is likely to be weak. Integrated care may uncover
      unmet need. Resolving this can benefit both individuals and society, but total
      care costs are likely to rise. Provided that integration delivers improvements in
      quality of life, even with additional costs, it may, nonetheless, offer value for
      money.

PMID- 25595288
TI  - Low IQ has become less important as a risk factor for early disability pension. A
      longitudinal population-based study across two decades among Swedish men.
AB  - BACKGROUND: Low IQ has been shown to be an important risk factor for disability
      pension (DP) but whether the importance has changed over time remains unclear. It
      can be hypothesised that IQ has become more important for DP over time in
      parallel with a more demanding working life. The aim of this study was to
      investigate the relative risk of low IQ on the risk of DP before age 30 between
      1971 and 2006. METHODS: This study covered the entire Swedish male population
      born between 1951 and 1976, eligible for military conscription. Information about
      the study subjects was obtained by linkage of national registers. Associations
      between IQ and DP over time were analysed by descriptive measures (mean values,
      proportions, etc) and by Cox proportional hazards regressions. Analyses were
      adjusted for educational level. RESULTS: The cohort consisted of 1 229 346 men.
      The proportion that received DP before the age of 30 increased over time, from
      0.68% in the cohort born between 1951 and 1955 to 0.95% in the cohort born
      between 1971 and 1976. The relative risk of low IQ (adjusted for education) in
      relation to high IQ decreased from 5.68 (95% CI 4.71 to 6.85) in the cohort born
      between 1951 and 1955 to 2.62 (95% CI 2.25 to 3.05) in the cohort born between
      1971 and 1976. CONCLUSIONS: Our results gave no support to the idea that the
      importance of low IQ for the risk of DP has increased in parallel with increasing
      demands in working life. In fact, low IQ has become less important as a risk
      factor for DP compared with high IQ between the early 1970s and 1990s. An
      increased educational level over the same time period is likely to be part of the
      explanation.

PMID- 25595289
TI  - Long noncoding RNA profiles of adrenocortical cancer can be used to predict
      recurrence.
AB  - Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of
      recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an
      important role in cancer development. Pathogenesis of adrenal tumours have been
      characterised by mRNA, microRNA and methylation expression signatures, but it is
      unknown if this extends to lncRNAs. This study describes lncRNA expression
      signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC)
      and presents lncRNAs associated with ACC recurrence to identify novel prognostic
      and therapeutic targets. RNA was extracted from freshly frozen tissue with
      confirmation of diagnosis by histopathology. Focused lncRNA and mRNA
      transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0
      microarray. Differentially expressed lncRNAs were validated using quantitative
      reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21
      samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA
      expression between each group. A total of 956 lncRNAs were differentially
      expressed between ACC and NAC, including known carcinogenesis-related lncRNAs
      such as H19, GAS5, MALAT1 and PRINS (P<=0.05); 85 lncRNAs were differentially
      expressed between ACC and ACA (P<=0.05). Hierarchical clustering and heat mapping
      showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six
      differentially expressed lncRNAs were found to be associated with ACC recurrence
      (P<=0.05), one of which, PRINS, was validated in a group of 20 ACCs and also
      found to be associated with metastatic disease on presentation. The pathogenesis
      of adrenal tumours extends to lncRNA dysregulation and low expression of the
      lncRNA PRINS is associated with ACC recurrence. 

PMID- 25595290
TI  - Kinesio taping in musculoskeletal pain and disability that lasts for more than 4
      weeks: is it time to peel off the tape and throw it out with the sweat? A
      systematic review with meta-analysis focused on pain and also methods of tape
      application.
AB  - INTRODUCTION: In recent years, Kinesio tape has been used to support injured
      muscle and joints, and relieve pain. We compared the pain and disability in
      individuals with chronic musculoskeletal pain who were treated with Kinesio
      taping with those using minimal or other treatment approaches. METHODS: Searches
      of eight major electronic databases were conducted. Data for pain and disability
      scores were extracted. Meta-analyses (wherever possible) with either a fixed or
      random effect(s) model, standardised mean differences (SMDs) and tests of
      heterogeneity were performed. RESULTS: Seventeen clinical-controlled trials were
      identified and included in the meta-analyses. When compared to minimal
      intervention, Kinesio taping provided superior pain relief (pooled SMD=-0.36, 95%
      CI -0.64 to -0.09, p=0.009) but the pooled disability scores were not
      significantly different (pooled SMD=-0.41, 95% CI -0.83 to 0.01, p=0.05). No
      significant differences were found when comparing Kinesio taping to other
      treatment approaches for pain (pooled SMD=-0.44, 95% CI -1.69 to 0.82, p=0.49)
      and disability (pooled SMD=0.08, 95% CI -0.27 to 0.43, p=0.65). DISCUSSION:
      Kinesio taping is superior to minimal intervention for pain relief. Existing
      evidence does not establish the superiority of Kinesio taping to other treatment
      approaches to reduce pain and disability for individuals with chronic
      musculoskeletal pain.

PMID- 25595291
TI  - Quantifying capital goods for biological treatment of organic waste.
AB  - Materials and energy used for construction of anaerobic digestion (AD) and
      windrow composting plants were quantified in detail. The two technologies were
      quantified in collaboration with consultants and producers of the parts used to
      construct the plants. The composting plants were quantified based on the
      different sizes for the three different types of waste (garden and park waste,
      food waste and sludge from wastewater treatment) in amounts of 10,000 or 50,000
      tonnes per year. The AD plant was quantified for a capacity of 80,000 tonnes per
      year. Concrete and steel for the tanks were the main materials for the AD plant.
      For the composting plants, gravel and concrete slabs for the pavement were used
      in large amounts. To frame the quantification, environmental impact assessments
      (EIAs) showed that the steel used for tanks at the AD plant and the concrete
      slabs at the composting plants made the highest contribution to Global Warming.
      The total impact on Global Warming from the capital goods compared to the
      operation reported in the literature on the AD plant showed an insignificant
      contribution of 1-2%. For the composting plants, the capital goods accounted for
      10-22% of the total impact on Global Warming from composting. 

PMID- 25595292
TI  - Effect of pyrolysis temperature on chemical and physical properties of sewage
      sludge biochar.
AB  - The objective of this study was to evaluate the effects of pyrolysis temperatures
      (300, 400, 500, 600 and 700 degrees C) on properties of biochar produced from an
      urban sewage sludge. Biochar yield significantly decreased from 72.5% at 300
      degrees C to 52.9% at 700 degrees C, whereas an increase in temperature increased
      the gas yield. Biochar pH and electrical conductivity increased by 3.8 and 1.4 dS
      m-1, proportionally to the increment of temperature. Biochar produced at low
      temperatures had higher total nitrogen and total organic carbon content but a
      lower C/N ratio, calcium carbonate equivalent, and total P, K and Na contents.
      Total and diethylene triamine penta acetic acid (DTPA)-extractable concentrations
      of Fe, Zn, Cu, Mn, Ni, Cr and Pb increased with increment of temperature. Lower
      DTPA-extractable concentrations of Fe, Zn, Cu, Mn, Ni and Pb were found in
      biochars compared to the sewage sludge. Pyrolysis decreased bulk density, whereas
      particle density and porosity increment was observed upon pyrolysis with
      increment of temperature. Sewage sludge saturated water content (thetas ) was
      130.4 g 100g-1 and significantly greater than biochar, but biochar thetas
      significantly increased with temperature (95.7 versus 105.4 g 100g-1 at 300 and
      700 degrees C, respectively). Pyrolysis decreased the biochar's water repellency,
      assessed by molarity of ethanol droplet (MED), compared to the sewage sludge. The
      lowest MED of 0.2 and water repellency rating of 3 were found for the biochar
      produced at 700 degrees C. Based on our results and considering the energy
      consumption, pyrolysis temperature in the range of 300-400 degrees C may be
      suggested for sewage sludge pyrolysis.

PMID- 25595293
TI  - Insights into the molecular recognition of the granuphilin C2A domain with
      PI(4,5)P2.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a key player in regulating
      the process of excytosis, including insulin secretion. Granuphilin, a tandem C2
      domain containing protein, mediates the docking of insulin granules onto plasma
      membrane. The C2A domain plays key roles in this process through interaction with
      PI(4,5)P2. In this study, we have investigated the molecular recognition
      mechanism of granuphilin-C2A domain to PI(4,5)P2 head group, and further to
      PI(4,5)P2-nanodisc by NMR, ITC, MST and SEC methods. Our results demonstrate that
      PI(4,5)P2 binds to the concave surface of granuphilin-C2A domain. The key
      residues involved in the binding were validated by mutation analysis. 

PMID- 25595295
TI  - Development and psychometric properties of a scale assessing the needs of
      caregivers of children with disabilities.
AB  - BACKGROUND: Planning and evaluation of health care services for children with
      disabilities requires information on their caregivers' needs. OBJECTIVE: This
      paper aims to present the development and psychometric properties of the
      Caregiver Needs Scale (CNS), a scale assessing the needs of caregivers of
      children with disabilities aged 0-12 years in Malaysia. METHODS: Development of
      the scale went through a multistage process of literature review, modification of
      an existing instrument, input from experts and feedback from service users.
      Literature review identified content domains and response options. An exploratory
      factor analysis (EFA) was undertaken to identify subscales of caregiver needs.
      The internal consistency reliability, convergent validity and discriminant
      validity of the new scale were examined. RESULTS: 273 caregivers of children with
      disabilities completed the fielded questionnaire. EFA revealed 4 subscales of
      caregiver needs: need for 'Help getting information and services for the child,'
      'Help coping with the child,' 'Help getting child care' and 'Help with finances.'
      Three items with factor loading <0.4 were dropped. Cronbach's alpha coefficients
      of the subscales ranged from 0.813 to 0.903. Total CNS score correlated with
      number of child's needs and unmet needs. The score was also higher in families
      with financial and employment problems. CONCLUSION: A new instrument was
      developed to assess the needs of caregivers of children with disabilities for use
      in the Malaysian population. The CNS showed satisfactory psychometric properties
      but further examination is warranted to confirm its validity.

PMID- 25595294
TI  - Fluphenazine: from an isolated molecule to its interaction with lipid bilayers.
AB  - Fluphenazine (FPh) belongs to the phenothiazine family of compounds and exhibits
      a wide variety of biological effects, including antimutagenic, proapoptotic,
      antiproliferative and anti-multidrug resistance (MDR) activities. The ability of
      FPh to interact with lipid membranes can have a significant impact on its
      biological activities. However, the mechanisms involved in the interaction of FPh
      with lipid membranes are poorly understood. FTIR-ATR spectroscopy has been used
      in this study to visualize the interactions between FPh and a model lipid bilayer
      composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Subsequent
      interpretation of the temperature-dependent FTIR spectra obtained for FPh:DPPC
      systems containing different concentrations of FPh was efficiently supported by
      principal component analysis. 

PMID- 25595296
TI  - Examining treatment adherence among parents of children with autism spectrum
      disorder.
AB  - BACKGROUND: Children with Autism Spectrum Disorder (ASD) participate in a variety
      of treatments, including medication, behavioral, alternative and developmental
      treatments. Parent adherence to these treatments is crucial for positive child
      outcomes. OBJECTIVE: The current study: 1) Explored patterns of parent adherence
      across the full range of treatments that are prescribed to children with ASD and,
      2) Examined whether parent demographics, parent treatment attitudes, and child
      ASD severity contribute to parents' adherence across ASD treatments. METHOD:
      Questionnaires were distributed to parents of children with ASD in a southeastern
      state. Parents (N = 274) were included if they were parenting a child with ASD
      who was receiving treatment for ASD symptoms. Paired t-tests and multiple linear
      regression were used to assess the study aims. RESULTS: Adherence to medication
      treatment was significantly greater than adherence to behavioral, developmental,
      or alternative treatments (adjusted p-values 0.0006, 0.0030, 0.0006
      respectively). Perceived family burden of a treatment was associated with lower
      adherence to medication, developmental, and alternative treatments. Finally,
      greater ASD severity was associated with lower adherence to alternative
      treatments. CONCLUSION: Overall, the independent variables accounted for more
      variance in adherence to medication and alternative treatments than in behavioral
      and developmental treatments. Parents' adherence to ASD treatment differs
      significantly by treatment type and is influenced by parental perceptions of the
      burden of treatment on the family. These findings highlight the importance of
      understanding and addressing the impact of ASD treatment regimens on family life.

PMID- 25595297
TI  - National health surveillance of adults with disabilities, adults with
      intellectual and developmental disabilities, and adults with no disabilities.
AB  - BACKGROUND: People with disabilities experience worse health and poorer access to
      health care compared to people without disability. Large-scale health
      surveillance efforts have largely excluded adults with intellectual and
      developmental disability. This study expands knowledge of health status, health
      risks and preventative health care in a representative US sample comparing the
      health of adults with no disability to adults with intellectual and developmental
      disability and to adults with other types of disability. OBJECTIVES: The purposes
      of this study were (1) to identify disparities between adults with intellectual
      and developmental disability and adults with no disability and (2) compare this
      pattern of disparities to the pattern between adults with other types of
      disability and adults without disability. METHODS: This study compares health
      status, health risks and preventative health care in a national sample across
      three groups of adults: No Disability, Disability, and Intellectual and
      Developmental Disability. Data sources were the 2010 Behavior Risk Factor
      Surveillance Survey and the National Core Indicators Consumer Survey. RESULTS:
      Adults with disability and with intellectual and developmental disability were
      more likely to report being in poor health compared to adults without disability.
      Disability and intellectual and developmental disability conferred unique health
      risks and health care utilization patterns. CONCLUSIONS: Significant disparities
      in health and health care utilization were found for adults with disability and
      developmental disability relative to adults without disability. Disability
      training for health care providers and health promotion research that identifies
      disability as a demographic group is needed.

PMID- 25595298
TI  - Integrated options for the management of black root rot of strawberry caused by
      Rhizoctonia solani Kuhn.
AB  - An investigation was made to manage strawberry black root rot caused by
      Rhizoctonia solani (R. solani) through the integration of Trichoderma harzianum
      (T. harzianum) isolate STA7, mustard oil cake and Provax 200. A series of
      preliminary experiments were conducted to select a virulent isolate of R. solani,
      an effective isolate of T. harzianum, a suitable organic amendment, and a
      suitable fungicide before setting the experiment for integration. The
      pathogenicity of the selected four isolates of R. solani was evaluated against
      strawberry and isolate SR1 was selected as the test pathogen due to its highest
      virulent (95.47% mortality) characteristics. Among the 20 isolates of T.
      harzianum, isolate STA7 showed maximum inhibition (71.97%) against the test
      pathogen (R. solani). Among the fungicides, Provax-200 was found to be more
      effective at lowest concentration (100 ppm) and highly compatible with
      Trichoderma isolates STA7. In the case of organic amendments, maximum inhibition
      (59.66%) of R. solani was obtained through mustard oil cake at the highest
      concentration (3%), which was significantly superior to other amendments. Minimum
      percentages of diseased roots were obtained with pathogen (R.
      solani)+Trichoderma+mustard oil cake+Provax-200 treatment, while the highest was
      observed with healthy seedlings with a pathogen-inoculated soil. In the case of
      leaf and fruit rot diseases, significantly lowest infected leaves as well as
      fruit rot were observed with a pathogen+Trichoderma+mustard oil cake+Provax-200
      treatment in comparison with the control. A similar trend of high effectiveness
      was observed by the integration of Trichoderma, fungicide and organic amendments
      in controlling root rot and fruit diseases of strawberry. Single application of
      Trichoderma isolate STA7, Provax 200 or mustard oil cake did not show
      satisfactory performance in terms of disease-free plants, but when they were
      applied in combination, the number of healthy plants increased significantly. The
      result of the current study suggests the superiority of our integrated approach
      to control the sclerotia forming pathogen R. solani compared to the individual
      treatment either by an antagonist or by a fungicide or by mustard oil cake.

PMID- 25595299
TI  - Issues arising following a referral and subsequent wait for extraction under
      general anaesthetic: impact on children.
AB  - BACKGROUND: Untreated caries in young children can result in a referral for
      extraction in hospital under general anaesthetic (GA). This study aims to explore
      the impact of caries during the ensuing wait for GA on children resident in the
      North West of England. METHODS: The study involved 456 respondents referred to
      six hospitals in the Northwest of England. Over a two-month period each of these
      children/ families completed a questionnaire and gave permission to access their
      referral and consultation notes. RESULTS: Children (6.78 years old: 1.50 to
      16.42) had on average five teeth extracted (ranging from one to a full clearance,
      with all teeth removed). Sixty seven per cent of parents reported their child had
      been in pain, 26% reported schools days being missed and 38% having sleepless
      nights. The average time from referral to operation was 137 days. Results
      indicated that children could be in discomfort during their wait, as pain was
      experienced, on average, 14 days before the operation. Wait time significantly
      predicated the number of sleepless nights b = .004, t(340) = 2.276, p = .023.
      CONCLUSIONS: It is clear that pain, sleepless nights and missed school are a
      feature during a wait for dental GA and can be exacerbated by an extended wait.
      These data support the need for not only effective prevention of caries within
      primary care to reduce wait times and experience of GA but also effective
      management of pain and infection during a prolonged wait for treatment.

PMID- 25595300
TI  - Methods to study chaperone-mediated autophagy.
AB  - Chaperone-mediated autophagy (CMA) is a multistep process that involves selective
      degradation and digestion of a pool of soluble cytosolic proteins in lysosomes.
      Cytosolic substrates are selectively identified and targeted by chaperones to
      lysosomes where they are subsequently translocated into the organelle lumen
      through a dedicated CMA-associated lysosomal membrane receptor/translocation
      complex. CMA contributes to maintaining a functional proteome, through
      elimination of altered proteins, and participates in the cellular energetic
      balance through amino acid recycling. Defective or dysfunctional CMA has been
      associated with human pathologies such as neurodegeneration, cancer,
      immunodeficiency or diabetes, increasing the overall interest in methods to
      monitor this selective autophagic pathway. Here, we describe approaches used to
      study CMA in different experimental models. 

PMID- 25595301
TI  - Cigarette Smoking During Substance Use Disorder Treatment: Secondary Outcomes
      from a National Drug Abuse Treatment Clinical Trials Network study.
AB  - INTRODUCTION: The majority of patients enrolled in treatment for substance use
      disorders (SUDs) also use tobacco. Many will continue to use tobacco even during
      abstinence from other drugs and alcohol, often leading to smoking-related
      illnesses. Despite this, little research has been conducted to assess the
      influence of being a smoker on SUD treatment outcomes and changes in smoking
      during a treatment episode. METHODS: In this secondary analysis, cigarette
      smoking was evaluated in participants completing outpatient SUD treatment as part
      of a multi-site study conducted by the National Drug Abuse Treatment Clinical
      Trials Network. Analyses included the assessment of changes in smoking and
      nicotine dependence via the Fagerstrom Test for Nicotine Dependence during the 12
      week study among all smokers (aim #1), specifically among those in the
      experimental treatment group (aim #2), and the moderating effect of being a
      smoker on treatment outcomes (aim #3). RESULTS: Participants generally did not
      reduce or quit smoking throughout the course of the study. Among a sub-set of
      participants with higher baseline nicotine dependence scores randomized to the
      control arm, scores at the end of treatment were lower compared to the
      experimental arm, though measures of smoking quantity did not appear to decrease.
      Further, being a smoker was associated with poorer treatment outcomes compared to
      non-smokers enrolled in the trial. CONCLUSIONS: This study provides evidence that
      patients enrolled in community-based SUD treatment continue to smoke, even when
      abstaining from drugs and alcohol. These results add to the growing literature
      encouraging the implementation of targeted, evidence-based interventions to
      promote abstinence from tobacco among SUD treatment patients.

PMID- 25595302
TI  - The Relationship Between Drug Use, Drug-related Arrests, and Chronic Pain Among
      Adults on Probation.
AB  - The intersection between chronic health conditions, drug use, and treatment
      seeking behavior among adults in the criminal justice system has been largely
      understudied. This study examined whether chronic pain was associated with opiate
      use, other illicit drug use, and drug-related arrests in a sample of substance
      using probationers. We expected that probationers with chronic pain-related
      diagnoses would report more opiate use and drug-related arrests. This study used
      baseline data from 250 adults on probation in Baltimore, Maryland and Dallas,
      Texas who were participating in a larger clinical trial. Eighteen percent of
      probationers in this sample reported suffering from chronic pain. In bivariate
      analyses, probationers with chronic pain reported more drug-related arrests (t=
      1.81; p<0.05) than those without chronic pain. Multivariate analyses support the
      hypothesis that probationers who reported chronic pain were marginally more
      likely to use opiates (OR=2.37; 95% CI .89-1.05) and non-opiate illicit drugs
      (OR=3.11; 95% CI 1.03-9.39) compared to offenders without chronic pain. In
      summary, these findings suggest that adults under probation supervision who
      suffer from chronic pain may be involved in criminal activity (specifically, drug
      related criminal activity) in an effort to self-medicate their physical health
      condition(s). Screening probationers for chronic pain in the probation setting
      and referring these adults to pain management treatment may be an important step
      in advancing public safety. 

PMID- 25595303
TI  - Spectroscopic and computational characterization of laccases and their substrate
      radical intermediates.
AB  - Laccases are multicopper oxidases which oxidize a wide variety of aromatic
      compounds with the concomitant reduction of oxygen to water as by-product. Due to
      their high stability and biochemical versatility, laccases are key enzymes to be
      used as eco-friendly biocatalyst in biotechnological applications. The presence
      of copper paramagnetic species in the catalytic site paired with the substrate
      radical species produced in the catalytic cycle makes laccases particularly
      attractive to be studied by spectroscopic approaches. In this review, the
      potentiality of a combined multifrequency electron paramagnetic spectroscopy
      /computational approach to gain information on the nature of the catalytic site
      and radical species is presented. The knowledge at molecular level of the enzyme
      oxidative process can be of great help to model new enzymes with increased
      efficiency and robustness. 

PMID- 25595305
TI  - Developments in alternative treatments for organophosphate poisoning.
AB  - Organophosphosphates (OPs) are highly effective acetylcholinesterase (AChE)
      inhibitors that are used worldwide as cheap, multi-purpose insecticides. OPs are
      also used as chemical weapons forming the active core of G-series and V-series
      chemical agents including tabun, sarin, soman, cyclosarin, VX, and their chemical
      analogs. Human exposure to any of these compounds leads to neurotoxic
      accumulation of the neurotransmitter acetylcholine, resulting in abnormal nerve
      function and multiple secondary health complications. Suicide from deliberate
      exposure to OPs is particularly prevalent in developing countries across the
      world and constitutes a major global health crisis. The prevalence and accessible
      nature of OP compounds within modern agricultural spheres and concern over their
      potential use in biochemical weapon attacks have incentivized both government
      agencies and medical researchers to enact stricter regulatory policies over their
      usage and to begin developing more proactive medical treatments in cases of OP
      poisoning. This review will discuss the research undertaken in recent years that
      has investigated new supplementary drug options for OP treatment and support
      therapy, including progress in the development of enzymatic prophylaxis. 

PMID- 25595304
TI  - Molecular basis of embryonic stem cell self-renewal: from signaling pathways to
      pluripotency network.
AB  - Embryonic stem cells (ESCs) can be maintained in culture indefinitely while
      retaining the capacity to generate any type of cell in the body, and therefore
      not only hold great promise for tissue repair and regeneration, but also provide
      a powerful tool for modeling human disease and understanding biological
      development. In order to fulfill the full potential of ESCs, it is critical to
      understand how ESC fate, whether to self-renew or to differentiate into
      specialized cells, is regulated. On the molecular level, ESC fate is controlled
      by the intracellular transcriptional regulatory networks that respond to various
      extrinsic signaling stimuli. In this review, we discuss and compare important
      signaling pathways in the self-renewal and differentiation of mouse, rat, and
      human ESCs with an emphasis on how these pathways integrate into ESC-specific
      transcription circuitries. This will be beneficial for understanding the common
      and conserved mechanisms that govern self-renewal, and for developing novel
      culture conditions that support ESC derivation and maintenance. 

PMID- 25595307
TI  - What is the Significance of Indeterminate Pulmonary Nodules in Patients
      Undergoing Resection for Pancreatic Adenocarcinoma?
AB  - OBJECTIVE: The significance of indeterminate pulmonary nodules (IPNs) in patients
      undergoing resection of pancreatic ductal adenocarcinoma (PDAC) is unknown. We
      sought to define the prevalence and impact of IPN in such patients. METHODS: We
      studied all patients who underwent surgical resection of PDAC between 1980 and
      2013. IPN was defined as >=1 well-defined lung nodule(s) less than 3 cm in
      diameter. Survival was assessed using univariate and multivariate Cox models.
      RESULTS: Of the 2306 resected patients, 374 (16.2 %) had a preoperative chest
      computed tomography (CT) scan. Of these patients, 183 (49 %) had >=1 IPN.
      Demographic and clinicopathological characteristics were similar among patients
      with or without IPN (all P>0.05). Median survival was comparable among patients
      who did (15.6 months) or did not (18.0 months) have IPN (P=0.66). Of the 183
      patients with IPN, 29 (16 %) progressed to clinically recognizable metastatic
      lung disease compared to 13 % without IPN (P=0.38). The presence of >1 IPN was
      associated with the development of lung metastasis (relative risk 1.58, 95 % CI
      1.03-2.4; P=0.05). However, lung metastasis was not associated with survival
      (P=0.24). CONCLUSIONS: An IPN proved to be a lung metastasis in only one of six
      patients with PDAC undergoing surgical resection in this study. Survival was not
      impacted, even among patients who developed lung metastasis. Patients with PDAC
      who have IPN should not be precluded from surgical consideration.

PMID- 25595308
TI  - A randomized trial of goal directed vs. standard fluid therapy in cytoreductive
      surgery with hyperthermic intraperitoneal chemotherapy.
AB  - The use of adequate fluid therapy during cytoreductive surgery (CRS) and
      hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. The aim
      of the study was to assess whether the use of fluid therapy protocol combined
      with goal-directed therapy (GDT) is associated with a significant change in
      morbidity, length of hospital stay, and mortality compared to standard fluid
      therapy. Patients American Society of Anesthesiologists (ASA) II-III undergoing
      CRS and HIPEC were randomized into two groups. The GDT group (N = 38) received
      fluid therapy according to a protocol guided by monitored hemodynamic parameters.
      The control group (N = 42) received standard fluid therapy. We evaluated
      incidence of major complications, total length of hospital stay, total amount of
      fluids administered, and mortality rate. The incidence of major abdominal
      complications was 10.5% in GDT group and 38.1% in the control group (P = 0.005).
      The median duration of hospitalization was 19 days in GDT group and 29 days in
      the control group (P < 0.0001). The mortality rate was zero in GDT group vs. 9.5%
      in the control group (P = 0.12). GDT group received a significantly (P < 0.0001)
      lower amount of fluid (5812 +/- 1244 ml) than the control group (8269 +/- 1452
      ml), with a significantly (P < 0.0001) lower volume of crystalloids (3884 +/-
      1003 vs. 68,528 +/- 1413 ml). In CRS and HIPEC, the use of a GDT improves outcome
      in terms of incidence of major abdominal and systemic postoperative complications
      and length of hospital stay, compared to standard fluid therapy protocol.

PMID- 25595309
TI  - Segmental duodenal resection: indications, surgical techniques and postoperative
      outcomes.
AB  - INTRODUCTION: Segmental duodenal resections (DR) have been increasingly performed
      for the treatment of primary duodenal tumours. The aim of the study is to review
      the indications for, clinical and operative details, and outcomes of patients
      undergoing elective DR. MATERIAL AND METHODS: We retrospectively reviewed all
      patients who underwent elective segmental DR for the treatment of primary
      duodenal tumours, at a single institution between January 2007 and December 2013.
      Demographic data, clinical presentation, preoperative investigations, operative
      details, postoperative complications/mortality and histopathological results were
      recorded. RESULTS: In the study period, 11 duodenal resections were performed (7
      male, median age 61 years). Thirty-six percent of the patients presented with
      anaemia. Surgical resection included two or more segments in seven patients. The
      most frequently resected part of the duodenum was segment 3 (n = 7). Median
      operative time was 191 min and blood loss was 675 ml. End-to-end and end-to-side
      anastomoses were performed in equal numbers. The pathology of resected specimens
      included adenocarcinoma (n = 4), gastrointestinal stromal tumour (GIST) (n = 1),
      adenoma (n = 5) and lymphoma (n = 1). Median hospital stay was 14 days. Overall,
      30-day morbidity rate was 82% (78% Clavien 2 or less). CONCLUSIONS: Segmental
      duodenal resection is a safe and effective surgical technique for the resection
      of primary duodenal tumours.

PMID- 25595311
TI  - VQone MATLAB toolbox: A graphical experiment builder for image and video quality
      evaluations: VQone MATLAB toolbox.
AB  - This article presents VQone, a graphical experiment builder, written as a MATLAB
      toolbox, developed for image and video quality ratings. VQone contains the main
      elements needed for the subjective image and video quality rating process. This
      includes building and conducting experiments and data analysis. All functions can
      be controlled through graphical user interfaces. The experiment builder includes
      many standardized image and video quality rating methods. Moreover, it enables
      the creation of new methods or modified versions from standard methods. VQone is
      distributed free of charge under the terms of the GNU general public license and
      allows code modifications to be made so that the program's functions can be
      adjusted according to a user's requirements. VQone is available for download from
      the project page (http://www.helsinki.fi/psychology/groups/visualcognition/).

PMID- 25595306
TI  - Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the pathogenesis
      and control of autoimmune arthritis.
AB  - The T helper (Th) cell subsets are characterized by the type of cytokines
      produced and the master transcription factor expressed. Th1 cells participate in
      cell-mediated immunity, whereas Th2 cells promote humoral immunity. Furthermore,
      the two subsets can control each other. Thereby, Th1-Th2 balance offered a key
      paradigm in understanding the induction and regulation of immune pathology in
      autoimmune and other diseases. However, over the past decade, Th17 cells
      producing interleukin-17 (IL-17) have emerged as the major pathogenic T cell
      subset in many pathological conditions that were previously attributed to Th1
      cells. In addition, the role of CD4+CD25+T regulatory cells (Treg) in controlling
      the activity of Th17 and other T cell subsets has increasingly been realized.
      Thereby, examination of the Th17/Treg balance in the course of autoimmune
      diseases has significantly advanced our understanding of the pathogenesis of
      these disorders. The differentiation of Th17 and Treg cells from naive T cells is
      inter-related and controlled in part by the cytokine milieu. For example,
      transforming growth factor beta (TGFbeta) is required for Treg induction, whereas
      the same cytokine in the presence of IL-6 (or IL-1) promotes the differentiation
      of Th17. Furthermore, IL-23 plays a role in the maintenance of Th17. Accordingly,
      novel therapeutic approaches are being developed to target IL-23/IL-17 as well as
      to modulate the Th17/Treg balance in favor of immune regulation to control
      autoimmunity. 

PMID- 25595310
TI  - Effect of hospital volume on outcomes of laparoscopic appendectomy for acute
      appendicitis: an observational study.
AB  - BACKGROUND: This study investigated the effect of hospital volume on outcomes of
      laparoscopic appendectomy for acute appendicitis. METHODS: In total, 30,525
      patients who underwent laparoscopic appendectomy for acute appendicitis were
      referred to 825 hospitals in Japan from 2010 to 2012. We compared appendectomy
      related complications, length of stay (LOS), and medical costs in relation to
      hospital volume. For this study period, hospitals were categorized as low-volume
      hospitals (LVHs, <50 cases), medium-volume hospitals (MVHs, 50-100 cases), or
      high-volume hospitals (HVHs, >100 cases). RESULTS: Significant differences in
      appendectomy-related complications were observed among the LVHs, MVHs, and HVHs
      (6.9, 7.2, and 6.0 %, respectively; p = 0.001). Multiple logistic regression
      revealed that HVHs were associated with a lower relative risk of appendectomy
      related complications than were LVHs and MVHs (odds ratio [OR], 0.84; 95 %
      confidence interval [CI], 0.74-0.95; p = 0.006). Multiple linear regression
      showed that HVHs were associated with shorter LOS and lower medical costs than
      were LVHs and MVHs. The unstandardized coefficient for LOS was -0.92 days (95 %
      CI, -1.07 to -0.78; p < 0.001), whereas that for medical costs was - $167.4 (95 %
      CI, -256.2 to -78.6; p < 0.001). CONCLUSIONS: Hospital volume was significantly
      associated with laparoscopic appendectomy outcomes.

PMID- 25595312
TI  - The protective effect of Moringa oleifera leaves against cyclophosphamide-induced
      urinary bladder toxicity in rats.
AB  - Cyclophosphamide (CP), an alkylating antineoplastic agent is widely used in the
      treatment of solid tumors and B-cell malignant disease. It is known to cause
      urinary bladder damage due to inducing oxidative stress. Moringa oleifera (Mof)
      is commonly known as drumstick tree. Moringa leaves have been reported to be a
      rich source of beta-carotene, protein, vitamin C, calcium, and potassium. It acts
      as a good source of natural antioxidants; due to the presence of various types of
      antioxidant compounds such as ascorbic acid, flavonoids, phenolics and
      carotenoids. The aim of this work was to test the possible antioxidant protective
      effects of M. oleifera leaves against CP induced urinary bladder toxicity in
      rats. Female Wister albino rats were divided into 4 groups. Group I served as
      control, received orally normal saline, group II received a single dose CP
      100mg/kg intraperitoneally, group III and VI both received orally hydroethanolic
      extract of Mof; 500 mg/kg and 1000 mg/kg respectively daily for a week, 1h before
      and 4h after CP administration. Rats were sacrificed 24h after CP injection. The
      bladder was removed, sectioned, and subjected to light, transition electron
      microscopic studies, and biochemical studies (measuring the parameter of lipid
      peroxidation; malondialdehyde along with the activities of the antioxidant enzyme
      reduced glutathione). The bladders of CP treated rats showed ulcered mucosa,
      edematous, hemorrhagic, and fibrotic submucosa by light microscopy.
      Ultrastructure observation showed; losing large areas of uroepithelium, extended
      intercellular gaps, junction complexes were affected as well as damage of
      mitochondria in the form of swelling and destruction of cristae. Biochemical
      analysis showed significant elevation of malondialdhyde, while reduced
      glutathione activity was significantly lowered. From the results obtained in this
      work, we can say that Moringa leaves play an important role in ameliorating and
      protecting the bladder from CP toxicity.

PMID- 25595313
TI  - Effects of matrix metalloproteinase 13 on vascular smooth muscle cells migration
      via Akt-ERK dependent pathway.
AB  - Migration of vascular smooth muscle cells (VSMCs) is an early event of
      atherosclerosis, which is mediated mainly by matrix metalloproteinase (MMP) 2 and
      9. Because MMP13 is associated with tumor cells migration, we hypothesized that
      MMP13 participates in VSMC migration induced by certain stimuli such as platelet
      derived growth factor (PDGF) and angiotensin II (Ang II). We found that the mRNA
      level of MMP13 in rat aortic smooth muscle cells (RAoSMCs) was increased by both
      PDGF and Ang II. We observed the significant decrease of migration in PDGF- or
      Ang II-treated RAoSMCs by MMP13 specific inhibitor treatment. Silencing of MMP13
      by a specific small interfering RNA (siRNA) significantly decreased expression of
      the active form of MMP13, which is followed by the decreased migration of PDGF-
      or Ang II-treated RAoSMCs. Interestingly, we observed synergistic inhibitory
      effects on migration by treatment with MMP2 and 13 or MMP9 and 13 inhibitors
      compared with that in single treatments. Moreover, we found that cordycepin, a
      known inhibitor of VSMC migration, caused significant downregulation of MMP2, 9,
      and 13 expression in PDGF-treated RAoSMCs. We further show that the expression
      level of MMP13 was significantly decreased by the treatment of Akt or ERK
      specific inhibitor in PDGF-treated RAoSMCs. Together, our data strongly suggest
      that MMP13 involves VSMCs migration via an Akt and ERK-dependent regulation
      [corrected].

PMID- 25595314
TI  - Antibiotic resistance and genotype of beta-lactamase producing Escherichia coli
      in nosocomial infections in Cotonou, Benin.
AB  - BACKGROUND: Beta lactams are the most commonly used group of antimicrobials
      worldwide. The presence of extended-spectrum lactamases (ESBL) affects
      significantly the treatment of infections due to multidrug resistant strains of
      gram-negative bacilli. The aim of this study was to characterize the beta
      lactamase resistance genes in Escherichia coli isolated from nosocomial
      infections in Cotonou, Benin. METHODS: Escherichia coli strains were isolated
      from various biological samples such as urine, pus, vaginal swab, sperm, blood,
      spinal fluid and catheter. Isolated bacteria were submitted to eleven usual
      antibiotics, using disc diffusion method according to NCCLS criteria, for
      resistance analysis. Beta-lactamase production was determined by an acidimetric
      method with benzylpenicillin. Microbiological characterization of ESBL enzymes
      was done by double disc synergy test and the resistance genes TEM and SHV were
      screened by specific PCR. RESULTS: ESBL phenotype was detected in 29 isolates
      (35.5%). The most active antibiotic was imipenem (96.4% as susceptibility rate)
      followed by ceftriaxone (58.3%) and gentamicin (54.8%). High resistance rates
      were observed with amoxicillin (92.8%), ampicillin (94%) and
      trimethoprim/sulfamethoxazole (85.7%). The genotype TEM was predominant in ESBL
      and non ESBL isolates with respectively 72.4% and 80%. SHV-type beta-lactamase
      genes occurred in 24.1% ESBL strains and in 18.1% of non ESBL isolates.
      CONCLUSION: This study revealed the presence of ESBL producing Eschericiha coli
      in Cotonou. It demonstrated also high resistance rate to antibiotics commonly
      used for infections treatment. Continuous monitoring and judicious antibiotic
      usage are required.

PMID- 25595315
TI  - Reduction of gastrointestinal symptoms in Parkinson's disease after a switch from
      oral therapy to rotigotine transdermal patch: a non-interventional prospective
      multicenter trial.
AB  - INTRODUCTION: Gastrointestinal (GI) symptoms are common among patients with
      Parkinson's disease (PD), due to both the disease itself and anti-PD drugs. We
      hypothesized that transdermal drug administration may result in fewer GI
      problems. This prospective observational study (ClinicalTrials.gov: NCT01159691)
      investigated effect of switching to rotigotine transdermal patch from oral anti
      PD medications in patients with PD and existing GI symptoms. METHODS: Patients
      were enrolled if their physician was planning to switch them to rotigotine
      because of GI symptoms experienced while receiving oral anti-PD medications.
      Effectiveness assessments included a visual analog scale (VAS) measuring
      intensity of GI symptoms from 0 (no disorder) to 100 mm (extremely severe
      disorder), a questionnaire on the frequency and intensity of six individual GI
      complaints (heartburn, bloating, nausea, vomiting, abdominal pain, diarrhea),
      each rated 0-12 for a sum score of 0-72, and patient satisfaction regarding GI
      symptoms over approximately 6 weeks after switching. RESULTS: Of 75 patients who
      received rotigotine, 58 had follow-up data available for final analysis.
      Intensity of GI complaints improved numerically on both the VAS (47.5 +/- 24.4 mm
      [n = 65] at baseline, 19.7 +/- 23.3 mm [n = 58] after around 6 weeks) and the sum
      score of GI complaints (11.2 +/- 9.0 at baseline, 2.1 +/- 4.4 [n = 58] after
      around 6 weeks). Fifty of 58 patients were "satisfied" or "very satisfied"
      regarding GI symptoms over around 6 weeks following switch to the patch.
      CONCLUSION: This study suggests that a switch from oral anti-PD medications to
      rotigotine transdermal patch may improve existing GI symptoms among patients with
      PD. Additional controlled studies are needed to confirm this finding.

PMID- 25595316
TI  - The first Japanese familial case of spinocerebellar ataxia 23 with a novel
      mutation in the PDYN gene.

PMID- 25595317
TI  - Dyskinesias during levodopa-carbidopa intestinal gel (LCIG) infusion: Management
      inclinical practice.

PMID- 25595319
TI  - Testing the anniversary reaction: causal effects of bereavement in a nationwide
      follow-up study from Sweden.
AB  - Lingering grief associated with the death of a loved one has been hypothesized to
      precipitate acute health events among survivors on anniversary dates. We sought
      to study excess mortality risk in parents around the death date and birth date of
      a deceased child as an indication of a "bereavement effect". We conducted a
      population based follow-up study using Swedish registries including links between
      children and parents. All biological and Swedish-born parents who experienced the
      death of a minor child born were observed during the period 1973-2008 (n =
      48,666). An increased mortality risk was found during the week of a child's death
      among mothers who lost a child aged 0-17 years (SMRR = 1.46, 95% CI 0.98-2.17).
      The association was stronger among mothers who lost a child aged 1-17 years (SMRR
      = 1.89, 95% CI 0.97-3.67) as compared to those who lost an infant (SMRR = 1.29,
      95% CI 0.78-2.12). Cardiovascular diseases and suicides were overrepresented as
      causes of death in mothers who died around the anniversary. We found no
      significant increase in the mortality risk around the date of child's birth, nor
      any suggestion of excess mortality risk among fathers, but rather a depression of
      paternal death (SMRR = 0.60, 95% CI 0.34-1.03). Our study indicates an
      anniversary reaction among mothers who lost a young child. These results suggest
      that bereavement per se could have an effect on health and mortality which should
      be acknowledged by public health professionals working with bereaved people.

PMID- 25595321
TI  - A modified suture technique for hemorrhage during cesarean delivery complicated
      by complete placenta previa.
AB  - OBJECTIVE: To assess the usefulness of a modified suture to treat postpartum
      bleeding among patients with complete placenta previa (CPP). METHODS: An
      observational study was conducted at Beijing Chaoyang Hospital, Beijing, China,
      among patients with CPP (with or without placenta accreta) who were enrolled from
      January 1 to March 31, 2014. During surgery, a Foley catheter balloon containing
      60-120 mL of water was used to compress the hemorrhage site and an absorbable
      suture was placed around the lower uterus segment to provide extra pressure on
      the balloon. RESULTS: Seven women with CPP underwent the procedure. The median
      hemostatic time was 4.6 minutes (range 3.0-7.0). The median estimated blood loss
      during surgery was 480 mL (range 400-600) for deliveries not complicated with
      placenta accreta and 1250 mL (range 1000-1500) for women with placenta accreta.
      Active bleeding was stopped after application of the modified suture; blood loss
      was less than 100mL in all cases in the 24 hours after surgery. CONCLUSION: The
      modified suture technique provided an easy and efficient surgical choice for
      women with CPP, especially among those with placenta accreta.

PMID- 25595320
TI  - Association of coffee consumption and CYP1A2 polymorphism with risk of impaired
      fasting glucose in hypertensive patients.
AB  - Whether and how coffee use influences glucose metabolism is still a matter for
      debate. We investigated whether baseline coffee consumption is longitudinally
      associated with risk of impaired fasting glucose in a cohort of 18-to-45 year old
      subjects screened for stage 1 hypertension and whether CYP1A2 polymorphism
      modulates this association. A total of 1,180 nondiabetic patients attending 17
      hospital centers were included. Seventy-four percent of our subjects drank
      coffee. Among the coffee drinkers, 87% drank 1-3 cups/day (moderate drinkers),
      and 13% drank over 3 cups/day (heavy drinkers). Genotyping of CYP1A2 SNP was
      performed by real time PCR in 639 subjects. At the end of a median follow-up of
      6.1 years, impaired fasting glucose was found in 24.0% of the subjects. In a
      multivariable Cox regression coffee use was a predictor of impaired fasting
      glucose at study end, with a hazard ratio (HR) of 1.3 (95% CI 0.97-1.8) in
      moderate coffee drinkers and of 2.3 (1.5-3.5) in heavy drinkers compared to
      abstainers. Among the subjects stratified by CYP1A2 genotype, heavy coffee
      drinkers carriers of the slow *1F allele (59%) had a higher adjusted risk of
      impaired fasting glucose (HR 2.8, 95% CI 1.3-5.9) compared to abstainers whereas
      this association was of borderline statistical significance among the homozygous
      for the A allele (HR 1.7, 95% CI 0.8-3.8). These data show that coffee
      consumption increases the risk of impaired fasting glucose in hypertension
      particularly among carriers of the slow CYP1A2 *1F allele.

PMID- 25595318
TI  - The global impact of non-communicable diseases on healthcare spending and
      national income: a systematic review.
AB  - The impact of non-communicable diseases (NCDs) in populations extends beyond ill
      health and mortality with large financial consequences. To systematically review
      and meta-analyze studies evaluating the impact of NCDs (including coronary heart
      disease, stroke, type 2 diabetes mellitus, cancer (lung, colon, cervical and
      breast), chronic obstructive pulmonary disease and chronic kidney disease) at the
      macro-economic level: healthcare spending and national income. Medical databases
      (Medline, Embase and Google Scholar) up to November 6th 2014. For further
      identification of suitable studies, we searched reference lists of included
      studies and contacted experts in the field. We included randomized controlled
      trials, systematic reviews, cohorts, case-control, cross-sectional, modeling and
      ecological studies carried out in adults assessing the economic consequences of
      NCDs on healthcare spending and national income without language restrictions.
      All abstracts and full text selection was done by two independent reviewers. Any
      disagreements were resolved through consensus or consultation of a third
      reviewer. Data were extracted by two independent reviewers using a pre-designed
      data collection form. Studies evaluating the impact of at least one of the
      selected NCDs on at least one of the following outcome measures: healthcare
      expenditure, national income, hospital spending, gross domestic product (GDP),
      gross national product, net national income, adjusted national income, total
      costs, direct costs, indirect costs, inpatient costs, outpatient costs, per
      capita healthcare spending, aggregate economic outcome, capital loss in
      production levels in a country, economic growth, GDP per capita (per capita
      income), percentage change in GDP, intensive growth, extensive growth,
      employment, direct governmental expenditure and non-governmental expenditure.
      From 4,364 references, 153 studies met our inclusion criteria. Most of the
      studies were focused on healthcare related costs of NCDs. 30 studies reported the
      economic impact of NCDs on healthcare budgets and 13 on national income.
      Healthcare expenditure for cardiovascular disease (12-16.5 %) was the highest;
      other NCDs ranged between 0.7 and 7.4 %. NCD-related health costs vary across the
      countries, regions, and according to type of NCD. Additionally, there is an
      increase in costs with increased severity and years lived with the disease. Low-
      and middle-income (LMI) countries were the focus of just 16 papers, which
      suggests an information shortage concerning the true economic burden of NCDs in
      these countries. NCDs pose a significant financial burden on healthcare budgets
      and nations' welfare, which is likely to increase over time. However further work
      is required to standardize more consistently the methods available to assess the
      economic impact of NCDs and to involve (hitherto under-addressed) LMI populations
      across the globe.

PMID- 25595322
TI  - Satisfaction with diagnosis process for gestational diabetes mellitus and risk
      perception among Australian women.
AB  - OBJECTIVE: To evaluate satisfaction with diagnosis, risk perceptions, and health
      beliefs among women with gestational diabetes mellitus (GDM). METHODS: In a cross
      sectional questionnaire-based study, participants with GDM diagnosed after
      26weeks of pregnancy were recruited from hospital-based services at Monash Health
      (Melbourne, VIC, Australia) and through newspaper advertisements between 2008 and
      2010. Eligible participants-aged at least 18years and able to read English
      completed a questionnaire. RESULTS: Among 46 women who completed the
      questionnaire, 38 (83%) were satisfied with the explanation of the GDM screening
      test and 31 (67%) felt that the results were explained well. Generally, women
      were satisfied with the information provided about lifestyle management (29 [81%]
      of 36) and medical therapy (26 [72%] of 36). Most women (41 [89%]) associated
      poor GDM control with perinatal complications. Additionally, many participants
      thought that insulin (35 [76%]) and lifestyle changes (30 [65%]) could reduce
      macrosomia. A total of 37 (82%) of 45 women perceived that they were at risk of
      future GDM, and 33 (73%) thought they had an increased risk of type 2 diabetes.
      Most women believed that they could change these risks (29 [64%] and 37 [82%] of
      45, respectively). CONCLUSION: Women were largely positive about their experience
      of GDM diagnosis. Explanation of the screening test and provision of information
      could be improved. Risk perception was reasonable.

PMID- 25595324
TI  - Epithelial-mesenchymal transition in human cancer: comprehensive reprogramming of
      metabolism, epigenetics, and differentiation.
AB  - The epithelial-mesenchymal transition (EMT) is a developmental process that is
      important for embryogenesis, wound healing, organ fibrosis, and cancer
      metastasis. Cancer-associated EMT is not a simple process to acquire migration
      and invasion ability, but a complicated and comprehensive reprogramming, involved
      in metabolism, epigenetics and differentiation, through which differentiated
      epithelial cancer cells reverse to an undifferentiated state, not only expressing
      stem cell markers, but also acquiring stem cell-like functions. Here we review
      recent ideas and discoveries that illustrate the links among metabolism,
      epigenetics, and dedifferentiation during EMT, with special emphasis on the
      primary driving force and ultimate goal of cancer-associated EMT - of the energy
      and for the energy. Furthermore, we highlight on the specificity of epigenetic
      modification during EMT, with an aim to explain how the repression of epithelial
      genes and activation of mesenchymal genes are coordinated simultaneously through
      EMT. Finally, we provide an outlook on anti-EMT therapeutic approach on
      epigenetic and metabolic levels, and discuss its potential for clinical
      application.

PMID- 25595325
TI  - Prevention of Babesia canis in dogs: efficacy of a fixed combination of
      permethrin and fipronil (Effitix(r)) using an experimental transmission blocking
      model with infected Dermacentor reticulatus ticks.
AB  - BACKGROUND: Two experimental studies using a transmission blocking model with
      Dermacentor reticulatus ticks infected with Babesia canis were performed to test
      the ability of Effitix(r) to prevent the transmission of babesiosis in dogs.
      METHODS: Four groups of seven dogs (experiment 1) and one group of eight dogs
      (experiment 2) were treated topically with a novel combination of fipronil and
      permethrin in a spot-on formulation (Effitix(r), Virbac) respectively 28, 21, 14
      and 7 days (experiment 1) and 2 days (experiment 2) prior to tick infestation. In
      each study, a control group of seven dogs (experiment 1) and eight dogs
      (experiment 2) remained untreated. On day 0, all dogs were infested with adult
      D.reticulatus ticks harboring B. canis. An efficacy failure (successfully
      infected) was regarded as a dog in the treated groups that was tested
      serologically positive for B.canis antibodies, using an indirect fluorescent
      antibody (IFA) assay and tested positive for B.canis by DNA-assay using PCR
      analysis. RESULTS: B.canis was transmitted by D.reticulatus to all untreated dogs
      (experiment 1) and six untreated dogs out of eight (experiment 2) as confirmed by
      IFA and PCR assays. The large majority of treated dogs (92.9% in experiment 1 and
      100% in experiment 2) remained sero-negative over the challenge period.
      CONCLUSIONS: The treatment of dogs with Effitix(r) applied 2 to 28 days prior to
      infestation with D. reticulatus harboring B.canis, successfully prevented the
      transmission of canine babesiosis.

PMID- 25595326
TI  - Parotid gland shrinkage during IMRT predicts the time to Xerostomia resolution.
AB  - PURPOSE: To assess the impact of mid-treatment parotid gland shrinkage on long
      term xerostomia during IMRT for oropharyngeal SCC. METHODS AND MATERIALS: All
      patients treated with IMRT at a single Institution from November 2007 to June
      2010 and undergoing weekly CT scans were selected. Parotid glands were contoured
      retrospectively on the mid treatment CT scan. For each parotid gland, the percent
      change relative to the planning volume was calculated and combined as weighted
      average. Patients were considered to be xerostomic if developed GR2+ dry mouth
      according to CTCAE v3.0. Predictors of the time to xerostomia resolution or
      downgrade to 1 were investigated at both uni- and multivariate analysis. RESULTS:
      85 patients were selected. With a median follow up of 35.8 months (range: 2.4
      62.6 months), the actuarial rate of xerostomia is 26.2% (SD: 5.3%) and 15.9% (SD:
      5.3%) at 2 and 3 yrs, respectively. At multivariate analysis, mid-treatment
      shrink along with weighted average mean parotid dose at planning and body mass
      index are independent predictors of the time to xerostomia resolution. Patients
      were pooled in 4 groups based on median values of both mid-treatment shrink (cut
      off: 19.6%) and mean WA parotid pl-D (cut-off: 35.7 Gy). Patients with a higher
      than median parotid dose at planning and who showed poor shrinkage at mid
      treatment are the ones with the outcome significantly worse (3-yr rate of
      xerostomia ~ 50%) than the other three subgroups (3-yr rate of xerostomia ~ 10%).
      CONCLUSION: For a given planned dose, patients whose parotids significantly
      shrink during IMRT are less likely to be long-term supplemental fluids dependent.

PMID- 25595327
TI  - Expert recommendations on treating psoriasis in special circumstances.
AB  - INTRODUCTION AND OBJECTIVES: A great amount of information on systemic and
      biologic therapies for moderate to severe psoriasis is now available. However,
      applying the evidence in numerous clinical scenarios has engendered debate; under
      these circumstances, the consensus of experts is useful. MATERIAL AND METHODS: A
      scientific committee systematically reviewed the literature relevant to 5
      clinical scenarios. An online Delphi survey of dermatologists with experience
      treating moderate to severe psoriasis was then carried out in order to shed light
      on questions that remained unresolved by the available evidence. RESULTS: Twenty
      three dermatologists responded to the survey and consensus was reached on 37
      (56%) of the 66 statements proposed. These results led to consensus on various
      clinical situations even though firm evidence was lacking. Thus, intermittent
      therapeutic regimens and strategies for reducing the intensity of treatment are
      considered appropriate for optimizing biologic treatment and reducing costs. The
      measurement of drug and antidrug antibody levels should be included routinely
      when following patients on biologics to treat psoriasis. Concomitant psoriatic
      arthritis or a history of cardiovascular conditions will influence the choice of
      biologic; in these situations, an agent with anti-tumor necrosis factor
      properties will be preferred. Tailored management is important when the patient
      is pregnant or intends to conceive; drug half-life and disease severity are
      important factors to take into consideration in these scenarios. CONCLUSIONS: A
      combination of systematic review of the literature and structured discussion of
      expert opinion facilitates decision-making in specific clinical scenarios.

PMID- 25595328
TI  - Reproductive robustness differs between generalist and specialist maternal rabbit
      lines: the role of acquisition and allocation of resources.
AB  - BACKGROUND: Farm animals are normally selected under highly controlled, non
      limiting conditions to favour the expression of their genetic potential.
      Selection strategies can also focus on a single trait to favour the most
      'specialized' animals. Theoretically, if the environment provides enough
      resources, the selection strategy should not lead to changes in the interactions
      between life functions such as reproduction and survival. However, highly
      'specialized' farm animals can be required for breeding under conditions that
      differ largely from selection conditions. The consequence is a degraded ability
      of 'specialized' animals to sustain reproduction, production and health, which
      leads to a reduced lifespan. This study was designed to address this issue using
      maternal rabbit lines. A highly specialized line with respect to numerical
      productivity at weaning (called V) and a generalist line that originated from
      females with a long reproductive life (called LP) were used to study the
      strategies that these lines develop to acquire and use the available resources
      when housed in different environments. In addition, two generations of line V,
      generations 16 and 36, were available simultaneously, which contributed to better
      understand how selection criteria applied in a specific environment changed the
      interplay between functions related to reproduction and survival. RESULTS: We
      show that, under constrained conditions, line LP has a greater capacity for
      resource acquisition than line V, which prevents excessive mobilization of body
      reserves. However, 20 generations of selection for litter size at weaning did not
      lead to an increased capacity of nutrient (or resource) acquisition. For the two
      generations of line V, the partitioning of resources between milk production,
      body reserves preservation or repletion or foetal growth differed. CONCLUSIONS:
      Combining foundational and selection criteria with a specific selection
      environment resulted in female rabbits that had a different capacity to deal with
      environmental constraints. An increased robustness was considered as an emergent
      property of combining a multiple trait foundational criterion with a wide range
      of environmental conditions. Since such a strategy was successful to increase the
      robustness of female rabbits without impairing their productivity, there is no
      reason that it should not be applied in other livestock species.

PMID- 25595329
TI  - Human mesenchymal stromal cells suppress T-cell proliferation independent of heme
      oxygenase-1.
AB  - Mesenchymal stromal cells deploy immune suppressive properties amenable for use
      as cell therapy for inflammatory disorders. It is now recognized that mesenchymal
      stromal cells necessitate priming with an inflammatory milieu, in particular
      interferon-gamma, to exert augmented immunosuppressive effects. It has been
      recently suggested that the heme-catabolizing enzyme heme oxygenase-1 is an
      essential component of the mesenchymal stromal cell-driven immune suppressive
      response. Because mesenchymal stromal cells upregulate indoleamine 2,3
      dioxygenase expression on interferon-gamma priming and indoleamine 2,3
      dioxygenase requires heme as a cofactor for optimal catabolic function, we
      investigated the potential antagonism of heme oxygenase-1 activity on indoleamine
      2, 3-dioxygenase and the impact on mesenchymal stromal cell immune plasticity. We
      herein sought to evaluate the molecular genetic effect of cytokine priming on
      human mesenchymal stromal cell heme oxygenase-1 expression and its functional
      role in differentially primed mesenchymal stromal cells. Contrary to previous
      reports, messenger RNA and protein analyses demonstrated that mesenchymal stromal
      cells derived from normal subjects (n = 6) do not express heme oxygenase-1 at
      steady state or after interferon-gamma, tumor necrosis factor-alpha, and/or
      transforming growth factor-beta priming. Pharmacological inhibition of heme
      oxygenase-1 with the use of tin protoporphyrin did not significantly abrogate the
      ability of mesenchymal stromal cells to suppress T-cell proliferation in vitro.
      Overall, these results unequivocally demonstrate that under steady state and
      after cytokine priming, human mesenchymal stromal cells immunoregulate T-cell
      proliferation independent of heme oxygenase-1.

PMID- 25595323
TI  - Sex steroid signaling: implications for lung diseases.
AB  - There is increasing recognition that sex hormones (estrogen, progesterone, and
      testosterone) have biological and pathophysiological actions in peripheral, non
      reproductive organs, including the lung. Clinically, sex differences in the
      incidence, morbidity and mortality of lung diseases such as asthma, chronic
      obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and
      pulmonary hypertension have been noted, although intrinsic sex differences vs.
      the roles of sex steroids are still not well-understood. Accordingly, it becomes
      important to ask the following questions: 1) Which sex steroids are involved? 2)
      How do they affect different components of the lung under normal circumstances?
      3) How does sex steroid signaling change in or contribute to lung disease, and in
      this regard, are sex steroids detrimental or beneficial? As our understanding of
      sex steroid signaling in the lung improves, it is important to consider whether
      such information can be used to develop new therapeutic strategies to target lung
      diseases, perhaps in both sexes or in a sex-specific manner. In this review, we
      focus on the basics of sex steroid signaling, and the current state of knowledge
      regarding how they influence structure and function of specific lung components
      across the life span and in the context of some important lung diseases. We then
      summarize the potential for sex steroids as useful biomarkers and therapeutic
      targets in these lung diseases as a basis for future translational research in
      the area of gender and individualized medicine.

PMID- 25595330
TI  - Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal
      tissue regeneration.
AB  - BACKGROUND AIMS: Periodontal tissue regeneration with the use of mesenchymal
      stromal cells (MSCs) has been regarded as a future cell-based therapy. However,
      low survival rates and the potential tumorigenicity of implanted MSCs could
      undermine the efficacy of cell-based therapy. The use of conditioned media from
      MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim
      of this study was to confirm the effect of MSC-CM on periodontal regeneration.
      METHODS: MSC-CM were collected during their cultivation. The concentrations of
      the growth factors in MSC-CM were measured with the use of enzyme-linked
      immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured
      in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of
      osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were
      quantified by means of real-time reverse transcriptase-polymerase chain reaction
      analysis. In vivo, periodontal defects were prepared in the rat models and the
      collagen sponges with MSC-CM were implanted. RESULTS: MSC-CM includes insulin
      like growth factor-1, vascular endothelial growth factor, transforming growth
      factor-beta1 and hepatocyte growth factor. In vitro, wound-healing and
      angiogenesis increased significantly in MSC-CM. The levels of expression of
      osteogenetic- and angiogenic-related genes were significantly upregulated in
      rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after
      implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1
      positive cells occurring frequently. At 4 weeks after implantation, regenerated
      periodontal tissue was observed in MSC-CM groups. CONCLUSIONS: The use of MSC-CM
      may be an alternative therapy for periodontal tissue regeneration because several
      cytokines included in MSC-CM will contribute to many processes of complicated
      periodontal tissue regeneration.

PMID- 25595332
TI  - Supervisor Autonomy and Considerate Leadership Style are Associated with
      Supervisors' Likelihood to Accommodate Back Injured Workers.
AB  - PURPOSE: To determine the association between supervisors' leadership style and
      autonomy and supervisors' likelihood of supporting job accommodations for back
      injured workers. METHODS: A cross-sectional study of supervisors from Canadian
      and US employers was conducted using a web-based, self-report questionnaire that
      included a case vignette of a back-injured worker. Autonomy and two dimensions of
      leadership style (considerate and initiating structure) were included as
      exposures. The outcome, supervisors' likeliness to support job accommodation, was
      measured with the Job Accommodation Scale (JAS). We conducted univariate analyses
      of all variables and bivariate analyses of the JAS score with each exposure and
      potential confounding factor. We used multivariable generalized linear models to
      control for confounding factors. RESULTS: A total of 796 supervisors
      participated. Considerate leadership style (beta = .012; 95% CI .009-.016) and
      autonomy (beta = .066; 95% CI .025-.11) were positively associated with
      supervisors' likelihood to accommodate after adjusting for appropriate
      confounding factors. An initiating structure leadership style was not
      significantly associated with supervisors' likelihood to accommodate (beta =
      .0018; 95% CI -.0026 to .0061) after adjusting for appropriate confounders.
      CONCLUSIONS: Autonomy and a considerate leadership style were positively
      associated with supervisors' likelihood to accommodate a back-injured worker.
      Providing supervisors with more autonomy over decisions of accommodation and
      developing their considerate leadership style may aid in increasing work
      accommodation for back-injured workers and preventing prolonged work disability.

PMID- 25595331
TI  - Should General Practitioners Issue a Sick Certificate to Employees Who Consult
      for Low Back Pain in Primary Care?
AB  - PURPOSE: Back pain is a common problem and has significant societal impact.
      Sickness certification is commonly issued to patients consulting their general
      practitioner with low back pain. The aim of this study was to investigate the
      association of certification for low back pain with clinical outcomes and cost
      consequences. METHODS: A prospective cohort study using linked questionnaire and
      medical record data from 806 low back pain patients in 8 UK general practices:
      comparison of 116 (14.4%) who received a sickness certificate versus 690 who did
      not receive certification. The primary clinical measure was the Roland and Morris
      Disability Questionnaire (RMDQ). Data on back pain consultation and work
      absenteeism were used to calculate healthcare and societal costs. RESULTS:
      Participants issued a sickness certificate had higher back-related disability at
      baseline consultation and 6-month follow-up [mean difference 3.1 (95% CI 1.8,
      4.4) on the RMDQ], indicating worse health status. After fully adjusting for
      baseline differences, most changes in clinical outcomes at 6 months were not
      significantly different between study groups. Productivity losses were
      significantly higher for the certification group, with most absence occurring
      after the expected end of certification; mean difference in costs due to
      absenteeism over 6 months was L1,956 (95% CI L941, L3040). CONCLUSIONS: There was
      no clear evidence of a difference in clinical outcomes between individuals issued
      a sickness certificate and those not issued a certification for their back pain.
      With little overall contrast in clinical outcomes, policy makers and care
      providers may wish to draw on the likely difference in societal costs alongside
      issues in ethical and moral care in their consideration of patient care for low
      back pain.

PMID- 25595334
TI  - cAMP modulation during sheep in vitro oocyte maturation delays progression of
      meiosis without affecting oocyte parthenogenetic developmental competence.
AB  - Removal of oocytes from their natural inhibitory follicular environment results
      in spontaneous resumption of meiosis independent of normal signaling events that
      occur in vivo. Controlling the onset of meiotic resumption via maintenance of
      elevated oocyte cAMP levels with adenylyl cyclase (AC) activation and
      phosphodiesterase (PDE) inhibition, and subsequent hormone stimulation with
      follicle FSH has been shown to dramatically improve developmental competence of
      bovine and murine IVM oocytes. This study evaluated the effect of cAMP modulation
      during IVM of sheep oocytes on meiotic progression and development to blastocyst
      after parthenogenetic activation. Changes in oocyte cAMP levels were quantified
      during the first 2h of in vitro maturation in control or cAMP-modulating medium.
      No significant changes in intra-oocyte cAMP were observed under control
      conditions, though a slight and transient drop was noticed at 15 min of
      maturation. Addition of the AC stimulator Forskolin and the PDE inhibitors IBMX
      altered the cAMP profile, resulting in 10-fold elevation of cAMP by 15 min and
      sustained >3-fold elevated levels from 30 to 120 min. The effect of cAMP
      elevation on meiotic resumption was measured by completion of germinal vesicle
      breakdown. Modulated oocytes were significantly delayed when compared to control
      media oocytes. Also, progression to MII was significantly delayed in modulated
      versus control oocytes at 20 and 24h, though no differences persisted to 28 h.
      Lastly, when control and modulated oocytes were parthenogenetically activated, no
      differences in blastocyst formation were observed. Thus, while cAMP modulation
      delayed meiotic progression, it did not improve developmental competence of sheep
      IVM oocytes.

PMID- 25595333
TI  - Cloning and functional characterization of nitrilase from Fusarium proliferatum
      AUF-2 for detoxification of nitriles.
AB  - A fungal nitrilase gene from Fusarium proliferatum AUF-2 was cloned through
      reverse transcription-PCR. The open reading frame consisted of 903 bp and
      potentially encoded a protein of 301 amino acid residues with a theoretical
      molecular mass of 33.0 kDa. The encoding gene was expressed in Escherichia coli
      strain BL21 and the recombinant protein with His6-tag was purified to
      electrophoretic homogeneity. The purified enzyme exhibited optimal activity in
      the range of 35-40  degrees C and pH 8.0. EDTA, Mg(2+), Zn(2+), Ca(2+), Fe(2+),
      Fe(3+) and Mn(2+) stimulated hydrolytic activity, whereas Cu(2+), Co(2+) and
      Ni(2+) had inhibitory effect on nitrilase activity. Ag(+) ions showed a strong
      inhibitory effect on the recombinant nitrilase activity. This nitrilase was
      specific towards aliphatic, heterocyclic and aromatic nitriles. The kinetic
      parameters V(max) and K(m) for benzonitrile substrate were determined to be 14.6
      MUmol/min/mg protein and 1.55 mM, respectively. Homology modelling and molecular
      docking studies provided an insight into the substrate specificity and the
      proposed catalytic triad for recombinant nitrilase consisted of Glu-54, Lys-133
      and Cys-175. This is the first report on the cloning and heterologous expression
      of nitrilase from Fusarium proliferatum.

PMID- 25595335
TI  - Age at onset of major depression and adulthood cardiovascular risk.
AB  - Childhood-onset compared to adulthood-onset of major depression is associated
      with increased rates of serious cardiovascular events, independently of
      cardiovascular risk factors. This could be explained by a longer duration of
      exposure to depression. Cardiovascular disease risk should be systematically
      assessed in individuals with long duration of major depression. 

PMID- 25595336
TI  - Measuring compulsive buying behaviour: psychometric validity of three different
      scales and prevalence in the general population and in shopping centres.
AB  - Due to the problems of measurement and the lack of nationally representative
      data, the extent of compulsive buying behaviour (CBB) is relatively unknown. The
      validity of three different instruments was tested: Edwards Compulsive Buying
      Scale (ECBS; Edwards, E.A., 1993. Development of a new scale for measuring
      compulsive buying behaviour. Financial Counseling and Planning. 4, 67-85),
      Questionnaire About Buying Behavior (QABB; Lejoyeux, M., Ades, J., 1994. Les
      achats pathologiques: une addiction comportementale. Neuro-Psy. 9, 25-32.) and
      Richmond Compulsive Buying Scale (RCBS; Ridgway, N.M., Kukar-Kinney, M., Monroe,
      K.B., 2008. An expanded conceptualization and a new measure of compulsive buying.
      Journal of Consumer Research. 35, 622-639.) using two independent samples. One
      was nationally representative of the Hungarian population (N=2710) while the
      other comprised shopping mall customers (N=1447). As a result, a new, four-factor
      solution for the ECBS was developed (Edwards Compulsive Buying Scale Revised
      (ECBS-R)), and confirmed the other two measures. Additionally, cut-off scores
      were defined for all measures. Results showed that the prevalence of CBB is 1.85%
      (with QABB) in the general population but significantly higher in shopping mall
      customers (8.7% with ECBS-R, 13.3% with QABB and 2.5% with RCBS-R). Conclusively,
      due to the diversity of content, each measure identifies a somewhat different CBB
      group. 

PMID- 25595337
TI  - A t(3;9)(q25.1;q34.3) translocation leading to OLFM1 fusion transcripts in Gilles
      de la Tourette syndrome, OCD and ADHD.
AB  - Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder with a strong
      genetic etiology; however, finding of candidate genes is hampered by its genetic
      heterogeneity and the influence of non-genetic factors on disease pathogenesis.
      We report a case of a male patient with GTS, obsessive compulsive disorder,
      attention-deficit/hyperactivity-disorder, as well as other comorbidities, and a
      translocation t(3;9)(q25.1;q34.3) inherited from a mother with tics. Mate-pair
      sequencing revealed that the translocation breakpoints truncated the olfactomedin
      1 (OLFM1) gene and two uncharacterized transcripts. Reverse-transcription PCR
      identified several fusion transcripts in the carriers, and OLFM1 expression was
      found to be high in GTS-related human brain regions. As OLFM1 plays a role in
      neuronal development it is a likely candidate gene for neuropsychiatric disorders
      and haploinsufficiency of OLFM1 could be a contributing risk factor to the
      phenotype of the carriers. In addition, one of the fusion transcripts may exert a
      dominant-negative or gain-of-function effect. OLFM1 is unlikely to be a major GTS
      susceptibility gene as no point mutations or copy number variants affecting OLFM1
      were identified in 175 additional patients. The translocation described is thus a
      unique event, but further studies in larger cohorts are required to elucidate
      involvement of OLFM1 in GTS pathogenesis. 

PMID- 25595340
TI  - Early signs of worry: psychosis risk symptom visual distortions are independently
      associated with suicidal ideation.
AB  - Previous studies have shown an association between suicidal behavior and
      schizophrenia. However, little is known about this association in those with
      psychotic experiences and symptoms that do not meet the criteria for full
      psychosis. The aim of the study was to investigate how psychosis risk symptoms
      are associated with suicidal ideation. Three-hundred and nine help-seeking
      adolescents (mean age 15.5 years) who were screened by an early intervention and
      detection team JERI in Helsinki University Central Hospital, Finland, were
      interviewed and asked to complete questionnaires of psychosis risk symptoms,
      suicidal ideation and depression. Psychosis risk symptoms were assessed by self
      report and confirmed by interview with questions from PROD-screen, depression was
      measured with BDI-II questionnaire and suicidal ideation was derived from BDI-II
      questionnaire. In a logistic regression analysis psychosis risk symptom visual
      distortions explained independently (OR 4.33; 95% CI 1.28-14.64) suicidal
      ideation when age, gender, depression and psychosis risk symptoms thought
      disorders, persecuting feelings and auditory distortions were controlled for.
      Results suggest that visual distortions are independently associated with
      suicidal ideation in young people. This finding should be taken into account in
      assessing help-seeking adolescents. 

PMID- 25595338
TI  - Vanillin-induced amelioration of depression-like behaviors in rats by modulating
      monoamine neurotransmitters in the brain.
AB  - Olfaction plays an important role in emotions in our daily life. Pleasant odors
      are known to evoke positive emotions, inducing relaxation and calmness. The
      beneficial effects of vanillin on depressive model rats were investigated using a
      combination of behavioral assessments and neurotransmitter measurements. Before
      and after chronic stress condition (or olfactory bulbectomy), and at the end of
      vanillin or fluoxetine treatment, body weight, immobility time on the forced
      swimming test and sucrose consumption in the sucrose consumption test were
      measured. Changes in these assessments revealed the characteristic phenotypes of
      depression in rats. Neurotransmitters were measured using ultrahigh-performance
      liquid chromatography. Our results indicated that vanillin could alleviate
      depressive symptoms in the rat model of chronic depression via the olfactory
      pathway. Preliminary analysis of the monoamine neurotransmitters revealed that
      vanillin elevated both serotonin and dopamine levels in brain tissue. These
      results provide important mechanistic insights into the protective effect of
      vanillin against chronic depressive disorder via olfactory pathway. This suggests
      that vanillin may be a potential pharmacological agent for the treatment of major
      depressive disorder. 

PMID- 25595339
TI  - Obesity correlates with fewer symptoms in schizophrenia treated with long-term
      clozapine: gender difference.

PMID- 25595341
TI  - Hemispheric asymmetries in auditory temporal integration: a study of event
      related potentials.
AB  - According to the asymmetric sampling in time hypothesis, the left auditory cortex
      processes stimuli using a short temporal integration window (~25-50 ms), whereas
      the right auditory cortex processes stimuli using a long temporal integration
      window (~200 ms). We examined N1 and T-complex responses to the second tone of
      tone-pairs presented with inter-stimulus intervals (ISIs) of 50 and 200 ms.
      Twenty-seven undergraduate students were presented with stimuli binaurally whilst
      the EEG was recorded. N1 and Ta responses were symmetric between hemispheres,
      with responses elicited by the second tone of the 50 ms ISI tone-pairs. Tb
      responses to the second tones were significantly attenuated over the right
      hemisphere when compared to the left hemisphere for the 50 ms ISI tone-pairs, but
      returned to similar amplitudes in the 200 ms condition. Our results suggest that
      temporal integration windows of the left and right primary auditory areas are
      symmetric whereas those of the left and right secondary auditory areas are
      asymmetric. These findings are consistent with the asymmetric sampling in time
      hypothesis and provide justification for further investigation of the involvement
      of temporal integration in higher order auditory processes.

PMID- 25595342
TI  - Dynamic expansion of alert responses to incoming painful stimuli following tool
      use.
AB  - Peripersonal space is the region closely surrounding our bodies. Within its
      boundaries, avoidance of threatening objects is crucial for surviving. Here we
      explored autonomic responses to painful stimuli with respect to the dynamic
      properties of the peripersonal space in healthy individuals. To this aim, in a
      series of experiments, we measured the Skin Conductance Response (SCR) to a
      noxious stimulus approaching and touching the hand, or stopping at different
      distances (far, near) from it. Results showed that the anticipatory response to
      an incoming threat is reduced if the stimulus targets a spatial position far away
      from the body, as compared to a near or bodily location. However, responses to
      far stimuli change if the boundaries of reachable space are extended further away
      by active tool use. Noteworthy, SCR is not influenced by a training consisting of
      a spatial attention task, without active tool use. This evidence sheds novel
      light on the adaptive role of peripersonal space, showing its importance for the
      coding of incoming threatening stimuli and its plasticity induced by contingent
      experience, such as tool use. 

PMID- 25595343
TI  - Trypanotoxic activity of thiosemicarbazone iron chelators.
AB  - Only a few drugs are available for treating sleeping sickness and nagana disease;
      parasitic infections caused by protozoans of the genus Trypanosoma in sub-Saharan
      Africa. There is an urgent need for the development of new medicines for
      chemotherapy of these devastating diseases. In this study, three newly designed
      thiosemicarbazone iron chelators, TSC24, Dp44mT and 3-AP, were tested for in
      vitro activity against bloodstream forms of Trypanosoma brucei and human
      leukaemia HL-60 cells. In addition to their iron chelating properties, TSC24 and
      Dp44mT inhibit topoisomerase IIalpha while 3-AP inactivates ribonucleotide
      reductase. All three compounds exhibited anti-trypanosomal activity, with minimum
      inhibitory concentration (MIC) values ranging between 1 and 100 uM and 50% growth
      inhibition (GI50) values of around 250 nM. Although the compounds did not kill HL
      60 cells (MIC values >100 uM), TSC24 and Dp44mT displayed considerable
      cytotoxicity based on their GI50 values. Iron supplementation partly reversed the
      trypanotoxic and cytotoxic activity of TSC24 and Dp44mT but not of 3-AP. This
      finding suggests possible synergy between the iron chelating and topoisomerase
      IIalpha inhibiting activity of the compounds. However, further investigation
      using separate agents, the iron chelator deferoxamine and the topoisomerase II
      inhibitor epirubicin, did not support any synergy for the interaction of iron
      chelation and topoisomerase II inhibition. Furthermore, TSC24 was shown to induce
      DNA degradation in bloodstream forms of T. brucei indicating that the mechanism
      of trypanotoxic activity of the compound is topoisomerase II independent. In
      conclusion, the data support further investigation of thiosemicarbazone iron
      chelators with dual activity as lead compounds for anti-trypanosomal drug
      development. 

PMID- 25595346
TI  - [Review of the latest guidelines of cardiometabolic disease. Introduction].

PMID- 25595345
TI  - Validation according to ISO/TS 12869:2012 of a molecular method for the isolation
      and quantification of Legionella spp. in water.
AB  - The aim of the present work was to validate the performances of a new molecular
      method comprehensive of water sample filtration, DNA extraction and Real-Time PCR
      for the quantification of Legionella spp. in clear water samples, in accordance
      with the recent ISO Technical Specification 12869:2012. All criteria and
      requirements were verified considering inclusivity and exclusivity, check of the
      calibration function, limit of detection and limit of quantification, recovery
      calculation, robustness and uncertainty of the entire method. The performances
      were validated as all parameters resulted to be in compliance with values
      detailed by the above mentioned standard. The described method proved to be
      specific, sensitive, accurate and it has been fully validated according to ISO/TS
      12869:2012. The possibility of using a validated molecular method will improve
      the reliability of the results making it a promising tool that should be used in
      addition to cultural analysis. Moreover, these findings make it particularly
      suitable for a relatively inexpensive screening of water samples, reducing the
      turnaround time and the workload. 

PMID- 25595347
TI  - [Guidelines for the management of hypertension].
AB  - In the last year, several scientific societies have published guidelines for the
      management of arterial hypertension. In Spain, two clinical practice guidelines
      have had a strong impact and have been closely followed in the last few years:
      the first is the Guideline of the National Heart, Lung and Blood Institute,
      although their last report (JNC 7) was published in 2003; the second is the
      clinical practice guideline for the management of arterial hypertension of the
      European Society of Cardiology (ESC) and the European Society of Hypertension
      (ESH), whose latest version was published in 2007, although an update was
      published in 2009. A new ESC/ESH document, published in 2013, adopts a mainly
      educational stance, closely rooted in clinical practice. Many of the
      recommendations maintain the same criteria as previous guidelines. However, the
      new publication shows greater rigor and contains major contributions such as
      specification of the level of evidence and grade of recommendation for each
      recommendation, which was lacking in the previous guidelines of these societies.
      The document is both practical and easy to consult, consisting of 17 tables, 5
      figures and 18 blocks of recommendations. The JNC 8 report, however, has a single
      objective: to respond to three questions that are considered a priority and which
      refer exclusively to drug therapy. Nine recommendations are made relating to
      these three questions. 

PMID- 25595348
TI  - [Guidelines for the management of diabetes mellitus type 2].
AB  - In the last few years, the publication of new studies in diabetes, together with
      the development of new classes of blood glucose-lowering medications, have led to
      updates of the most prestigious clinical practice guidelines for the treatment of
      diabetes. Thus, a consensus statement from the American Diabetes Association and
      the European Association for the Study of Diabetes on the management of
      hyperglycemia in type 2 diabetes was published in April 2012. An update of one of
      the evidence-based guidelines issued by the Canadian Diabetes Association
      appeared in 2013 and this year, 2014, saw the publication of the consensus
      document of the redGDPS, whose guidelines are those most closely followed by
      primary care physicians in Spain. The three guidelines highlight the need for an
      individualized approach to type 2 diabetes mellitus, outlining both target
      glycemic goals and distinct treatment regimens based on patient characteristics,
      disease stage and the presence of comorbidities or complications. In the
      treatment of the disease, the three guidelines also stress the importance of
      considering patients' opinions and of recommending lifestyle modifications to
      achieve good disease control. Metformin is identified as the first-line drug,
      with the addition of other glucose-lowering agents if necessary. 

PMID- 25595344
TI  - Imaging biomarkers in prostate cancer: role of PET/CT and MRI.
AB  - Prostate-specific antigen (PSA) is currently the most widely used biomarker of
      prostate cancer (PCa). PSA suggests the presence of primary tumour and disease
      relapse after treatment, but it is not able to provide a clear distinction
      between locoregional and distant disease. Molecular and functional imaging, that
      are able to provide a detailed and comprehensive overview of PCa extension, are
      more reliable tools for primary tumour detection and disease extension assessment
      both in staging and restaging. In the present review we evaluate the role of
      PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of
      these imaging modalities in prognosis, treatment planning and response
      assessment. Innovative imaging strategies including new radiotracers and hybrid
      scanners such as PET/MRI are also discussed. 

PMID- 25595349
TI  - [Guidelines for the management of dyslipidemia].
AB  - The AHA/ACC 2013 guideline on the treatment of blood cholesterol to reduce
      atherosclerotic cardiovascular disease (ASCVD) in adults contains major
      differences with the previous ESC/EAS 2011 guidelines and the remaining
      international guidelines, which has generated major controversies. The AHA/ACC
      document has developed a new model for estimating cardiovascular risk for primary
      prevention which is not comparable with the SCORE recommended in the European
      guidelines. This guideline does not establish a fixed target for low-density
      lipoprotein cholesterol (LDLc). Instead, it identifies 4 major statin benefit
      groups at risk for the development ASCVD, who should receive low-, moderate-, and
      high-intensity statin therapy to reduce LCLc. In contrast, the European
      guidelines maintain LDLc as the main treatment target and non-high-density
      lipoprotein cholesterol as a secondary treatment target. The document recommends
      calculating cardiovascular risk for the overall treatment of patients with
      dyslipidemia according to 4 risk levels (low, moderate, high, and very high),
      establishes LDLc treatment targets, and recommends a statin-based therapeutic
      strategy and other, lipid-lowering strategies, aimed at achieving these targets.
      The American guidelines cannot be extrapolated to the European population. Target
      based treatment, as recommended in the EAS/ESC guidelines, is the best strategy
      for Europe. In Spain, the Primary Care Guidelines of the Spanish Society of
      Family and Community Medicine (semFYC) and the Spanish Society of Primary Care
      Physicians (SEMERGEN) are based on the European recommendations. Finally, the
      Spanish Society of Arteriosclerosis (SEA), SEMERGEN, semFYC and the Spanish
      Society of General Medicine (SEMG) are reaching a consensus on the approach and
      management of patients with atherogenic dyslipidemia in primary care.

PMID- 25595350
TI  - Sense and sensibility: Swedish midwives' ambiguity to the use of synthetic
      oxytocin for labour augmentation.
AB  - The use of intravenous artificial oxytocin for augmentation of labour is very
      common in midwifery care in Sweden. Studies have shown that oxytocin is often
      administered to women in labour who have no signs of labour dystocia. It was the
      aim of this study to examine Swedish midwives' views on and experiences of labour
      augmentation in the context of normal labour. Individual interviews were carried
      out with 15 midwives from southern Sweden. The material was analysed using
      qualitative content analysis, which resulted in one theme: sense and sensibility
      and four main categories: permissible situations, motivating the decision,
      intervening in the birth process and iatrogenic awareness. The results showed
      that midwives expressed ambiguity about augmentation of labour. They were of the
      opinion that oxytocin was used very often and sometimes unnecessarily. There is
      awareness that interventions to augment labour can result in undesirable effects
      on the birth process. Despite this, deeper discussion of this problem was avoided
      in the interviews. Further research should focus on the process involved when
      midwives weigh pros and cons when deciding to augment labour. More knowledge is
      also needed about the barriers for optimal care in labour that are inherent in
      health-care systems. 

PMID- 25595351
TI  - Long-term efficacy of Nd:YAG laser photocoagulation vs. liquid paraffin plus
      antiseptic cream in the treatment of recurrent epistaxis.
AB  - The objective of this study was to evaluate the long-term efficacy of Nd:YAG
      laser photocoagulation with that of liquid paraffin plus antiseptic cream in the
      management of recurrent epistaxis. Eighty consecutive patients who suffered from
      recurrent anterior epistaxis presented to the Otolaryngology Department at the
      Eye and ENT Hospital, Fudan University between February 2011 and June 2011. These
      patients with histories of recurrent epistaxis were randomly assigned to receive
      treatment in an outpatient setting consisting of either a combination of liquid
      paraffin plus antiseptic cream (Group 1) or Nd:YAG laser photocoagulation (Group
      2). MAIN OUTCOME MEASURES: the following outcome measures were assessed: bleeding
      intensity; bleeding frequency 2 years after treatment (0 = no bleeding, 1 =
      reduced bleeding, 2 = the same, 3 = worse), participant's perception of
      discomfort during the management (grade 0-10, where 10 is the worst pain), and
      complications. Finally, 70 patients remain in our study. At 2 years, 86 % of
      laser patients versus 31 % of control patients had no reported bleeding. The
      outcome score at 2 years after treatment showed a significant difference between
      the two groups (P = 0.000, P < 0.01). The median and mean +/- SD pain levels
      experienced were 5.0 and 5.2 +/- 2.2. Both groups had no complications. It can be
      further concluded that Nd:YAG laser photocoagulation is a preferable therapy in
      the treatment of recurrent epistaxis in long-term efficacy. The level of pain
      associated with the procedure was well tolerated. It is a simple, easy, safe and
      rapid therapy, which can be performed in an office setting.

PMID- 25595352
TI  - Association between vitamin D concentration and levels of sex hormones in an
      elderly Polish population with different genotypes of VDR polymorphisms
      (rs10735810, rs1544410, rs7975232, rs731236).
AB  - BACKGROUND: Vitamin D co-regulates the synthesis of sex hormones in part by
      interaction with its nuclear receptor. The aim of this study was to determine
      whether there is an association of vitamin D concentration vs the level of sex
      hormones in elderly Polish individuals with different genotypes of the vitamin D
      receptor (VDR) gene. MATERIALS AND METHODS: Rs10735810, rs1544410, rs7975232, and
      rs731236 polymorphisms of VDR, the serum sex hormone level, free estrogen index
      (FEI) and free androgen index (FAI) as well as vitamin D, were evaluated in 766
      persons (362 women and 404 men) selected from 5695 Polish population, aged 65
      90years from the PolSenior survey. RESULTS: We observed that women with GG
      (rs731236), TT (rs7975232), BB (rs1544410) and FF (rs10735810) genotypes were
      characterized by a significant correlation between vitamin D vs testosterone
      concentration and FAI value. We found a significant correlation between
      testosterone level and FAI vs vitamin D concentration in men with heterozygote AG
      in the rs731236 polymorphism and in the GG (rs7975232), the BB (rs1544410), and
      the Ff (rs10735810) genotypes. CONCLUSION: In elderly selected Polish population
      with different genotypes of VDR polymorphisms, a statistically significant
      relationship between vitamin D concentration vs testosterone level was observed.

PMID- 25595353
TI  - Comparative genomic analysis of aspartic proteases in eight parasitic
      platyhelminths: insights into functions and evolution.
AB  - We performed genome-wide identifications and comparative genomic analyses of the
      predicted aspartic proteases (APs) from eight parasitic flatworms, focusing on
      their evolution, potentials as drug targets and expression patterns. The results
      revealed that: i) More members of family A01 were identified from the
      schistosomes than from the cestodes; some evidence implied gene loss events along
      the class Cestoda, which may be related to the different ways to ingest host
      nutrition; ii) members in family A22 were evolutionarily highly conserved among
      all the parasites; iii) one retroviral-like AP in family A28 shared a highly
      similar predicted 3D structure with the HIV protease, implying its potential to
      be inhibited by HIV inhibitor-like molecules; and iiii) retrotransposon
      associated APs were extensively expanded among these parasites. These results
      implied that the evolutionary histories of some APs in these parasites might
      relate to adaptations to their parasitism and some APs might have potential
      serving as intervention targets. 

PMID- 25595354
TI  - Erratum to: Failure of renal biomarkers to predict worsening renal function in
      high-risk patients presenting with oliguria.

PMID- 25595355
TI  - Formation of the early canine CL and the role of prostaglandin E2 (PGE2) in
      regulation of its function: an in vivo approach.
AB  - The mechanisms governing corpus luteum (CL) function in domestic dogs remain not
      fully elucidated. The upregulated expression of cyclooxygenase 2 and
      prostaglandin (PG) E2 synthase (PGES) at the beginning of the canine luteal phase
      indicated their luteotrophic roles, and the steroidogenic activity of PGE2 in the
      early canine CL has been confirmed in vitro. Recently, by applying a
      cyclooxygenase 2 (COX2)-specific inhibitor (firocoxib [Previcox]; Merial) from
      the day of ovulation until the midluteal phase, the luteotrophic effects of PGs
      have been shown in vivo. This is a follow-up study investigating the underlying
      endocrine mechanisms associated with the firocoxib-mediated effects on the canine
      CL. Experimental groups were formed with ovariohysterectomies performed on Days
      5, 10, 20, or 30 of firocoxib treatments (10 mg/kg bw/24h; TGs = treated groups).
      Untreated dogs served as controls. A decrease of steroidogenic acute regulatory
      (STAR) protein expression was observed in TGs. The expression of PGE2 synthase
      was significantly suppressed in TGs 5 and 10, and both PGE2 and PGF2alpha levels
      were decreased in luteal homogenates, particularly from CL in TG 5. Similarly,
      expression of the prolactin receptor (PRLR) was diminished in TGs 5 and 20. The
      expression of PGE2 receptors PTGER2 (EP2) and PTGER4 (EP4), the PG- transporter
      (PGT), and 15-hydroxy PG dehydrogenase (HPGD) was not affected in TGs. Our
      results substantiate a direct luteotrophic role of PGs in the early canine CL,
      i.e., by upregulating the steroidogenic machinery. Additionally, the possibility
      of an indirect effect on PRL function arises from the increased prolactin
      receptor expression in response to PGE2 treatment in canine lutein cells observed
      in vitro. 

PMID- 25595356
TI  - Soybean lecithin-based extender preserves spermatozoa membrane integrity and
      fertilizing potential during goat semen cryopreservation.
AB  - Soybean lecithin may represent a suitable alternative to egg yolk for semen
      cryopreservation in livestock species. However, additional studies are needed to
      elucidate its effects on spermatozoa functional properties. Semen collected from
      five Sarda bucks was cryopreserved in Tris-based extender and glycerol (4% v:v)
      with different supplementations. In a preliminary experiment, different soybean
      lecithin concentrations were tested (1%-6% wt/vol) and results in terms of
      viability, percentages of progressive motile and rapid spermatozoa, and DNA
      integrity after thawing showed that the most effective concentration was 1%. In
      the second experiment, semen was frozen in a Tris-based extender with no
      supplementation (EXT), with 1% lecithin (EXT LC), and 20% egg yolk (EXT EY). The
      effectiveness of these extenders was also compared with a commercial extender.
      The EXT EY led to the highest viability and motility parameters after freezing
      and thawing (P < 0.0001). No significant differences were observed in
      intracellular ATP concentrations. Additional molecular features revealed that
      sperm functionality was affected in EXT EY, as demonstrated by lower DNA and
      acrosome integrity (P < 0.05), and higher lipid peroxidation compared with
      spermatozoa cryopreserved in EXT LC (P < 0.0001). Results obtained in the
      heterologous in vitro fertilization test showed that EXT LC better preserved
      spermatozoa functionality, as demonstrated by the higher fertilization rates
      compared with the other media (66.2 +/- 4.5% for EXT LC vs. 32.7 +/- 4.5%, 38.7
      +/- 4.5%, 39.6 +/- 5.2% for EXT, EXT EY, and commercial extender; P < 0.01). The
      present study demonstrated that lecithin can be considered as a suitable
      alternative to egg yolk in goat semen cryopreservation, because it ensures higher
      fertilization rates and a better protection from membrane damage by cold shock. 

PMID- 25595357
TI  - Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in
      voided urine can be extracorporeally quantified using a spectrophotometer.
AB  - BACKGROUND: We evaluated the feasibility of photodynamic diagnosis of bladder
      cancer by spectrophotometric analysis of voided urine samples after
      extracorporeal treatment with 5-aminolevulinic acid (ALA). METHODS: Sixty-one
      patients with bladder cancer, confirmed histologically after the transurethral
      resection of a bladder tumor, were recruited as the bladder cancer group, and 50
      outpatients without history of urothelial carcinoma or cancer-related findings
      were recruited as the control group. Half of the voided urine sample was
      incubated with ALA (ALA-treated sample), and the rest was incubated without
      treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX
      levels, intensity of the samples at the excitation wavelength of 405 nm was
      measured using a spectrophotometer. The difference between the intensity of the
      ALA-treated and ALA-untreated samples at 635 nm was calculated. RESULTS: The
      differences in the bladder cancer group were significantly greater than those in
      the control group (p < 0.001). These differences were also significantly greater
      in patients with high-grade tumors than in those with low-grade tumors (p =
      0.004), and also in patients with invasive bladder cancer than in those with
      noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84.
      Sensitivity and specificity of the method were 82% and 80%, respectively.
      CONCLUSIONS: We demonstrated that protoporphyrin IX levels in urinary cells
      treated with ALA could be quantitatively detected by spectrophotometer in
      patients with bladder cancer. Therefore, this cancer detection system has a
      potential for clinical use.

PMID- 25595358
TI  - Person-centred care for patients with chronic heart failure - a cost-utility
      analysis.
AB  - BACKGROUND: Costs of care for patients with chronic heart failure have been
      estimated at between 1% and 2% of the total health care expenditure in Europe and
      North America. Two-thirds are for inpatient care. Person-centred care (PCC)
      asserts that patients are persons and should not be reduced to their diseases
      alone. AIMS: The aim of this study was to estimate the cost-utility of PCC when
      compared with conventional care in patients hospitalized for worsening chronic
      heart failure. METHODS AND RESULTS: Data for the cost-utility analysis were
      collected alongside a prospective clinical intervention study with a controlled
      before and after design from 2008 to 2010. Patient-specific resources used and
      preference-based health status data were collected at an individual level.Only
      63% received PCC as intended illustrating the difficulties of introducing new
      methods in established organizations. The group intended to have PCC yielded
      higher costs in comparison with the conventional care group. The incremental cost
      was estimated as ?98. The costs for those who actually received PCC, per protocol
      (PP) (63%) were significantly (p=0.026) lower than for those in the conventional
      care group, with an incremental cost-saving of ?863. For the first three months,
      patients in the conventional care group showed decreasing health-related quality
      of life, with a corresponding improvement in the PCC(PP) group. CONCLUSION: It
      must be emphasized, however, that these positive effects, both cheaper and
      somewhat better, were obtained only among those receiving the PCC intervention in
      its intended form, PCC(PP).

PMID- 25595359
TI  - Frailty Syndrome in cardiovascular disease: clinical significance and research
      tools.
AB  - Frailty Syndrome is one of the key health problems in geriatrics, strongly
      affecting poor prognosis. There is a growing interest in the relevance of this
      syndrome in cardiovascular disease. The diagnosis of Frailty Syndrome in the
      elderly cardiac population is essential for an accurate risk stratification and
      for making therapeutic decisions. Most risk assessment systems used in cardiology
      are based on chronological age, which does not always reflect the biological age
      of a patient, therefore making an inadequate risk estimation. This paper
      discusses the definitions of Frailty Syndrome and research tools used to identify
      it. We specifically address the role of Frailty Syndrome in cardiovascular
      disease and the diagnostic and therapeutic difficulties in patients with Frailty
      Syndrome, emphasizing the role of the identification of Frailty Syndrome in
      making therapeutic decisions and the stratification of cardiovascular risk in
      patients with cardiologic conditions. 

PMID- 25595360
TI  - Periprosthetic shoulder infection in the United States: incidence and economic
      burden.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is a major cause of morbidity
      after shoulder arthroplasty. PJI epidemiology has not been well studied. We aimed
      to analyze the historical incidence, predisposing factors, and economic burden of
      PJI after shoulder arthroplasty in the United States. METHODS: Primary shoulder
      arthroplasty patients were identified by the International Classification of
      Diseases, Ninth Revision, Clinical Modification codes 81.80 (total shoulder
      arthroplasty), 81.81 (hemiarthroplasty), and 81.88 (reverse arthroplasty) in the
      Nationwide Inpatient Sample from 2002 to 2011. PJI was identified by codes 80.01
      (arthrotomy for device removal) and 996.66 (prosthetic infection). Multivariate
      logistic regression analysis was used to identify predisposing factors for PJI.
      RESULTS: PJI rate was 0.98% from 2002 to 2011 and did not vary significantly.
      Comorbidities associated with PJI were weight loss/nutritional deficiency (odds
      ratio [OR], 2.62; 95% confidence interval [CI], 1.53-4.51; P = .00047), drug
      abuse (OR, 2.38; 95% CI, 1.41-4.02; P = .0011), and anemia from blood loss (OR,
      2.43; 95% CI, 1.50-3.93; P = .00031) or iron deficiency (OR, 2.05; 95% CI, 1.69
      2.49; P < .0001). Demographic factors associated with PJI were younger age (OR,
      1.020; 95% CI, 1.017-1.024; P < .0001) and male gender (OR, 1.961; 95% CI, 1.816
      2.117; P < .0001). In 2011, median hospitalization costs for PJI were $17,163.57
      compared with $16,132.68, $13,955.83, and $20,007.87 for total shoulder
      arthroplasty, hemiarthroplasty, and reverse arthroplasty, respectively.
      CONCLUSION: Increasing incidence of shoulder arthroplasty and a constant
      infection rate will result in greater overall PJI burden. Whereas hospitalization
      costs for PJI are comparable to those of primary arthroplasty, they are incurred
      after the original cost of shoulder arthroplasty. Certain identifiable patient
      variables correlate with higher PJI rates. Risk factor modification may decrease
      PJI incidence and help contain costs.

PMID- 25595361
TI  - Eponyms in elbow fracture surgery.
AB  - Eponyms are common in medicine and in orthopaedic surgery. For future reference
      and historical considerations, we present common eponyms in elbow fracture
      surgery. We describe in short the biography of the name giver and give, where
      possible, the original description on which the eponym was based. Whether eponyms
      should continue to be used is a question that remains unanswered, but if we use
      them, knowledge of the original description can prevent confusion and knowledge
      of the historical background sheds light on the interesting roots of our
      profession. 

PMID- 25595363
TI  - Deflating trees: improving Bayesian branch-length estimates using informed
      priors.
AB  - Prior distributions can have a strong effect on the results of Bayesian analyses.
      However, no general consensus exists for how priors should be set in all
      circumstances. Branch-length priors are of particular interest for phylogenetics,
      because they affect many parameters and biologically relevant inferences have
      been shown to be sensitive to the chosen prior distribution. Here, we explore the
      use of outside information to set informed branch-length priors and compare
      inferences from these informed analyses to those using default settings. For both
      the commonly used exponential and the newly proposed compound Dirichlet prior
      distributions, the incorporation of relevant outside information improves
      inferences for data sets that have produced problematic branch- and tree-length
      estimates under default settings. We suggest that informed priors are worthy of
      further exploration for phylogenetics. 

PMID- 25595362
TI  - Identification of shoulder osteoarthritis biomarkers: comparison between
      shoulders with and without osteoarthritis.
AB  - BACKGROUND: The biologic factors associated with shoulder osteoarthritis (OA)
      have not been elucidated. The purpose of this study was to investigate
      osteoarthritic biomarkers of the shoulder. To our knowledge, this is the first
      study to analyze shoulder cartilage for OA-associated genes and to examine human
      shoulder cartilage for a possible biomarker, connexin 43 (Cx43). MATERIALS AND
      METHODS: Cartilage from 16 osteoarthritic and 10 nonosteoarthritic humeral heads
      was assessed for expression of the following genes by real-time polymerase chain
      reaction: types I, II, and X collagen; matrix metalloproteinases (MMPs); tissue
      inhibitors of MMP (TIMPs); interleukins; versican; cyclooxygenase 2 (Cox-2);
      inducible nitric oxide synthase (iNOS); tumor necrosis factor alpha (TNF-alpha);
      aggrecanase 2 (ADAMTS5); and Cx43. RESULTS: In osteoarthritic shoulders, Cx43,
      Cox-2, versican, collagen type I, ADAMTS5, MMP-3, and TNF-alpha expressions were
      significantly increased compared with controls. TIMP-3 and iNOS trended toward
      significance, with robust expression in osteoarthritic shoulders and low
      expression in nonosteoarthritic shoulders. In osteoarthritic shoulders, gene
      expression of Cx43, ADAMTS5, collagen type I, Cox-2, versican, and TIMP-3 showed
      predominance (85-, 33-, 13-, 12-, 11.5-, and 3-fold increases, respectively)
      relative to nonosteoarthritic controls. Spearman correlation analysis showed
      significant correlations between Cx43 and collagen (types I, II, and X), MMP-9,
      TIMP-2 and TIMP-3, versican, Cox-2, iNOS, and ADAMTS5. CONCLUSIONS: Certain genes
      are markedly upregulated in osteoarthritic shoulders compared with
      nonosteoarthritic shoulders, with Cx43, Cox-2, versican, collagen type I,
      ADAMTS5, MMP-3, and TNF-alpha expression being significantly increased. These
      genes might be useful biomarkers for examining shoulder OA. CLINICAL RELEVANCE:
      Identification of osteoarthritic biomarkers can help us better understand
      shoulder OA and build the foundation for future research on disease progression
      and treatments.

PMID- 25595364
TI  - Hypotonic stress induces RANKL via transient receptor potential melastatin 3
      (TRPM3) and vaniloid 4 (TRPV4) in human PDL cells.
AB  - Bone remodeling occurs in response to various types of mechanical stress. The
      periodontal ligament (PDL) plays an important role in mechanical stress-mediated
      alveolar bone remodeling. However, the underlying mechanism at the cellular level
      has not been extensively studied. In this study, we investigated the effect of
      shear stress on the expression of bone remodeling factors, including receptor
      activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) and
      osteoprotegerin (OPG), as well as its upstream signaling pathway in primary human
      PDL cells. We applied hypotonic stress to reproduce shear stress to PDL cells.
      Hypotonic stress induced the messenger RNA (mRNA) and protein expression of RANKL
      but not OPG. It also increased intracellular Ca(2+) concentration ([Ca(2+)]i).
      Extracellular Ca(2+) depletion and nonspecific plasma membrane Ca(2+) channel
      blockers completely inhibited the increase in both [Ca(2+)]i and RANKL mRNA
      expression. We identified the expression and activation of transient receptor
      potential melastatin 3 (TRPM3) and vaniloid 4 (TRPV4) channels in PDL cells.
      Pregnenolone sulfate (PS) and 4alpha-phorbol 12, 13-didecanoate (4alpha-PDD),
      which are agonists of TRPM3 and TRPV4, augmented Ca(2+) influx and RANKL mRNA
      expression. Both pharmacological (2-aminoethoxydiphenyl borate [2-APB], ruthenium
      red [RR], ononetin [Ono], and HC 067047 [HC]) and genetic (small interfering RNA
      [siRNA]) inhibitors of TRPM3 and TRPV4 reduced the hypotonic stress-mediated
      increase in [Ca(2+)]i and RANKL mRNA expression. Our study shows that hypotonic
      stress induced RANKL mRNA expression via TRPM3- and TRPV4-mediated extracellular
      Ca(2+) influx and RANKL expression. This signaling pathway in PDL cells may play
      a critical role in mechanical stress-mediated alveolar bone remodeling. 

PMID- 25595365
TI  - Wntless regulates dentin apposition and root elongation in the mandibular molar.
AB  - Wnt signaling plays an essential role in the dental epithelium and mesenchyme
      during tooth morphogenesis. However, it remains unclear if Wnt ligands, produced
      from dental mesenchyme, are necessary for odontoblast differentiation and dentin
      formation. Here, we show that odontoblast-specific disruption of Wntless (Wls), a
      chaperon protein that regulates Wnt sorting and secretion, leads to severe
      defects in dentin formation and root elongation. Dentin thickness decreased
      remarkably and pulp chambers enlarged in the mandibular molars of OC
      Cre;Wls(CO/CO) mice. Although the initial odontoblast differentiation was normal
      in the mutant crown, odontoblasts became cuboidal and dentin thickness was
      reduced. In immunohistochemistry, Wnt10a, beta-catenin, type I collagen, and
      dentin sialoprotein were significantly down-regulated in the odontoblasts of
      mutant crown. In addition, roots were short and root canals were widened. Cell
      proliferation was reduced in the developing root apex of mutant molars.
      Furthermore, Wnt10a and Axin2 expression was remarkably decreased in the
      odontoblasts of mutant roots. Deletion of the Wls gene in odontoblasts appears to
      reduce canonical Wnt activity, leading to inhibition of odontoblast maturation
      and root elongation. 

PMID- 25595367
TI  - Probing crystal packing of uniformly (13)C-enriched powder samples using
      homonuclear dipolar coupling measurements.
AB  - The relationship between the crystal packing of powder samples and long-range
      (13)C-(13)C homonuclear dipolar couplings is presented and illustrated for the
      case of uniformly (13)C-enriched L-alanine and L-histidine.HCl.H2O. Dipolar
      coupling measurement is based on the partial reintroduction of dipolar
      interactions by spinning the sample slightly off-magic-angle, while the coupling
      of interest for a given spin pair is isolated with a frequency-selective pulse. A
      cost function is used to correlate the so-derived dipolar couplings to trial
      crystal structures of the samples under study. This procedure allowed for the
      investigation of the l-alanine space group and L-histidine.HCl.H2O space group
      and unit-cell parameters.

PMID- 25595366
TI  - Cardiac tissue slices: preparation, handling, and successful optical mapping.
AB  - Cardiac tissue slices are becoming increasingly popular as a model system for
      cardiac electrophysiology and pharmacology research and development. Here, we
      describe in detail the preparation, handling, and optical mapping of
      transmembrane potential and intracellular free calcium concentration transients
      (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in
      the epicardium-tangential plane contained well-aligned in-slice myocardial cell
      strands ("fibers") in subepicardial and midmyocardial sections. Cut with a high
      precision slow-advancing microtome at a thickness of 350 to 400 MUm, tissue
      slices preserved essential action potential (AP) properties of the precutting
      Langendorff-perfused heart. We identified the need for a postcutting recovery
      period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady
      state values for AP duration (APD) (identified by exponential fitting). There was
      no significant difference between the postcutting recovery dynamics in slices
      obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical
      uncouplers during the cutting process. A rapid increase in APD, seen after
      cutting, was caused by exposure to ice-cold solution during the slicing
      procedure, not by tissue injury, differences in uncouplers, or pH-buffers
      (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and
      conduction, a combination of multipoint and field stimulation should be used to
      avoid misinterpretation based on source-sink effects. In summary, we describe in
      detail the preparation, mapping, and data analysis approaches for reproducible
      cardiac tissue slice-based investigations into AP and CaT dynamics.

PMID- 25595369
TI  - Involuntary admission and treatment of patients with mental disorder.
AB  - Despite the efforts of the World Health Organization to internationally
      standardize strategies for mental-health care delivery, the rules and regulations
      for involuntary admission and treatment of patients with mental disorder still
      differ markedly across countries. This review was undertaken to describe the
      regulations and mental-health laws from diverse countries and districts of Europe
      (UK, Austria, Denmark, France, Germany, Italy, Ireland, and Norway), the Americas
      (Canada, USA, and Brazil), Australasia (Australia and New Zealand), and Asia
      (Japan and China). We outline the criteria and procedures for involuntary
      admission to psychiatric hospitals and to community services, illustrate the key
      features of laws related to these issues, and discuss their implications for
      contemporary psychiatric practice. This review may help to standardize the
      introduction of legislation that allows involuntary admission and treatment of
      patients with mental disorders in the mainland of China, and contribute to
      improved mental-health care. In this review, involuntary admission or treatment
      does not include the placement of mentally-ill offenders, or any other aspect of
      forensic psychiatry. 

PMID- 25595368
TI  - Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the
      progression of amnestic mild cognitive impairment?
AB  - Impaired structure and function of the hippocampus is a valuable predictor of
      progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease
      (AD). As a part of the medial temporal lobe memory system, the hippocampus is one
      of the brain regions affected earliest by AD neuropathology, and shows
      progressive degeneration as aMCI progresses to AD. Currently, no validated
      biomarkers can precisely predict the conversion from aMCI to AD. Therefore, there
      is a great need of sensitive tools for the early detection of AD progression. In
      this review, we summarize the specific structural and functional changes in the
      hippocampus from recent aMCI studies using neurophysiological and neuroimaging
      data. We suggest that a combination of advanced multi-modal neuroimaging measures
      in discovering biomarkers will provide more precise and sensitive measures of
      hippocampal changes than using only one of them. These will potentially affect
      early diagnosis and disease-modifying treatments. We propose a new sequential and
      progressive framework in which the impairment spreads from the integrity of
      fibers to volume and then to function in hippocampal subregions. Meanwhile, this
      is likely to be accompanied by progressive impairment of behavioral and
      neuropsychological performance in the progression of aMCI to AD. 

PMID- 25595370
TI  - Novel drug-delivery approaches to the blood-brain barrier.
AB  - The blood-brain barrier (BBB) maintains homeostasis by blocking toxic molecules
      from the circulation, but drugs are blocked at the same time. When the dose is
      increased to enhance the drug concentration in the central nervous system, there
      are side-effects on peripheral organs. In recent years, genetic therapeutic
      agents and small molecules have been used in various strategies to penetrate the
      BBB while minimizing the damage to systemic organs. In this review, we describe
      several representative methods to circumvent or cross the BBB, including chemical
      and physical strategies. 

PMID- 25595371
TI  - Mutagenicity and DNA-damaging potential of clenbuterol and its metabolite 4-amino
      3,5-dichlorobenzoic acid in vitro.
AB  - The aim of this study was to evaluate in vitro toxicity of clenbuterol and its
      metabolite 4-amino-3,5-dichlorobenzoic acid. Cytotoxicity and pro-oxidative
      effect of both compounds were studied on human colon adenocarcinoma cell line SW
      480. No significant cytotoxic effect of either compound was observed. Results of
      an Ames test on Salmonella typhimurium did not indicate mutagenic activity of
      clenbuterol on TA 98 and TA 100 strains, regardless of metabolic activation.
      Potential mutagenic effects of the highest clenbuterol concentration (2500 ng/ml)
      were observed on the TA 1535 strain. The obtained results of alkaline comet assay
      on isolated human lymphocytes suggested that both compounds induced an increase
      of primary DNA damage in a concentration-dependent manner. 4-ADBA was a slightly
      more potent inducer of primary DNA damage as compared to clenbuterol. Chromosomal
      aberration analysis showed that clenbuterol caused a statistically significant
      increase in the total number of aberrant cells only at the highest concentration
      tested (3% vs. 0.7% in the negative control). The results of this study might
      represent a solid frame for designing and planning future studies with both
      compounds, which should further clarify their mechanisms of action and
      genotoxic/cytogenetic effects relevant for human risk assessment. 

PMID- 25595372
TI  - Dominant lethal effects of nocodazole in germ cells of male mice.
AB  - The ability of the anticancer drug, nocodazole, to induce dominant lethal
      mutations in male germ cells was investigated by the in vivo dominant lethal
      test. Mice were treated with single doses of 15, 30 and 60 mg/kg nocodazole.
      These males were mated at weekly intervals to virgin females for 6 weeks.
      Nocodazole clearly induced dominant lethal mutations in the early spermatid stage
      with the highest tested dose. Mice treated with 60 mg/kg nocodazole showed an
      additional peak of dominant lethal induction in mature spermatozoa during the
      first week matings after treatment. The percentage sperm count and sperm motility
      were significantly decreased after treatment of males with 30 and 60 mg/kg
      nocodazole. Moreover, the middle and highest doses of nocodazole significantly
      increased the percentage of abnormal sperm. Our study provides evidence that
      nocodazole is a germ cell mutagen. Marked alteration in the spermiogram analysis
      after nocodazole treatment possibly confirms that nocodazole has a significant
      effect on sperm maturation and development during storage and transit. The
      demonstrated mutagenicity profile of nocodazole may support further development
      of effective chemotherapy with less mutagenicity. Moreover, the cancer patients
      and medical personnel exposed to this drug chemotherapy may stand a higher risk
      for abnormal reproductive outcomes. 

PMID- 25595373
TI  - Factors associated with willingness to participate in clinical trials: a
      nationwide survey study.
AB  - BACKGROUND: This study was conducted to investigate awareness of clinical trials
      (CTs) including perceptions of favorable feelings about, necessity for, and
      safety of CTs, the ultimate beneficiary of CTs and the factors associated with
      willingness to participate in CTs among the general population in South Korea.
      METHODS: A cross sectional survey study was conducted in a randomly selected
      national sample of 1,515 Korean. RESULTS: Perception toward CTs was measured
      using a scale from 0 (strongly disagree) to 10 (strongly agree). Respondents
      readily understood the necessity for CTs (M = 7.27, SD = 2.15); had moderately
      favorable feelings (M = 5.32, SD = 2.31) toward CTs and felt that these CTs were
      moderately safe (M =  .71, SD = 1.90). Twenty-five percent of the respondents
      answered that they would be willing to participate in a CT in the future.
      Perception of the ultimate benefits of CTs, awareness, favorable feelings,
      safety, and necessity regarding CTs were identified as significant predictors of
      willingness to participate in CTs. CONCLUSION: An awareness of CTs and the
      perceptions toward CTs were associated with general public willingness to
      participate in a CT. Findings from this study can be used in planning outreach
      and recruitment strategies, and to understand the predictors of CT participation.

PMID- 25595374
TI  - Pulmonary artery stenosis in hybrid single-ventricle palliation: High incidence
      of left pulmonary artery intervention.
AB  - OBJECTIVE: Pulmonary artery growth is an important determinant of outcome in
      single-ventricle strategies. Higher rates of pulmonary artery intervention have
      been reported with hybrid-based palliation when compared with Norwood palliation.
      METHODS: We performed a retrospective review of pulmonary artery growth and
      clinical outcomes in patients undergoing hybrid-based single-ventricle
      palliation. RESULTS: The stage I hybrid procedure was performed in 72 patients
      between 2004 and 2012, of whom 54 were on a Fontan palliative pathway. Thirty
      four infants completed stage II, and 20 infants underwent the Fontan operation.
      The mean diameters of the right pulmonary artery (5.6 +/- 1.9 mm) and left
      pulmonary artery (5.6 +/- 2.1 mm) were similar before stage II. After stage II,
      the right and left pulmonary artery diameters were 8.5 +/- 2.1 mm and 5.8 +/- 1.3
      mm, respectively (P < .001), and after the Fontan operation, these were 8.8 +/-
      2.0 mm and 6.4 +/- 1.1 mm, respectively (P = .002). The mean right pulmonary
      artery z score was normal throughout, but the left pulmonary artery did not
      maintain a normal size. The cumulative pulmonary artery intervention rate was 50%
      at any time after stage II. Fifteen interventions (88%) were performed after
      stage II (35% during the same hospitalization, 71% <60 days). The most intervened
      site was the midsection of the left pulmonary artery (41%). Initial pulmonary
      artery intervention was balloon dilation in 59% of patients and stent
      implantation in 41% of patients. Half of patients with initial balloon dilation
      required reintervention. CONCLUSIONS: There is significant risk of left pulmonary
      artery compromise after the second stage of hybrid palliation associated with a
      high intervention rate.

PMID- 25595375
TI  - Ex-utero intrapartum treatment as a novel bridging strategy to surgery in
      hypoplastic left heart syndrome with intact atrial septum-cross-circulation
      revisited.

PMID- 25595376
TI  - Effects of azithromycin and tanomastat on experimental bronchiolitis obliterans.
AB  - OBJECTIVE: Azithromycin has become a standard of care in therapy of bronchiolitis
      obliterans following lung transplantation. Matrix metalloprotease-9 broncho
      alveolar lavage levels increase in airway neutrophilia and bronchiolitis
      obliterans. Interleukin-17 may play a role in lung allograft rejection, and
      interleukin-12 is downregulated in bronchiolitis obliterans. Whether these
      mechanisms can be targeted by azithromycin remains unclear. METHODS:
      Bronchiolitis obliterans was induced by transplantation of Fischer F344 rat left
      lungs to Wistar Kyoto rats. Allografts with azithromycin therapy from day 1 to 28
      or 56 and mono- or combination therapy with the broad-spectrum matrix
      metalloprotease inhibitor tanomastat from day 1 to 56 were compared to control
      allografts and isografts. Graft histology was assessed, and tissue cytokine
      expression studied using Western blotting and immunofluorescence. RESULTS: The
      chronic airway rejection score in the azithromycin group did not change between 4
      and 8 weeks after transplantation, whereas it significantly worsened in control
      allografts (P = .041). Azithromycin+tanomastat prevented complete allograft
      fibrosis, which occurred in 40% of control allografts. Azithromycin reduced
      interleukin-17 expression (P = .049) and the number of IL-17(+)/CD8(+)
      lymphocytes at 4 weeks, and active matrix metalloprotease-9 at 8 weeks (P =
      .017), and increased interleukin-12 expression (P = .025) at 8 weeks following
      transplantation versus control allografts. CONCLUSIONS: The expression of
      interleukin-17 and matrix metalloprotease-9 in bronchiolitis obliterans may be
      attenuated by azithromycin, and the decrease in interleukin-12 expression was
      prevented by azithromycin. Combination of azithromycin with a matrix
      metalloprotease inhibitor is worth studying further because it prevented complete
      allograft fibrosis in this study.

PMID- 25595377
TI  - A high-fat diet is associated with altered adipokine production and a more
      aggressive esophageal adenocarcinoma phenotype in vivo.
AB  - OBJECTIVE: Obesity has been linked to esophageal adenocarcinoma (EAC). We
      hypothesize that adipokines, which are altered by obesity, could affect EAC
      growth rates and potentially serve as biomarkers of disease and targets for
      treatment. We have developed a potential murine model to investigate the effects
      of obesity-altered adipokines on EAC in vivo. METHODS: Severe combined immune
      deficient mice were fed either a high-fat diet (HFD) containing 60% animal fat,
      or a control diet with 10% animal fat, and monitored for weight gain for 5 weeks.
      All mice were subcutaneously implanted with EAC cells (OE33), and tumor volume
      was monitored for an additional 4 weeks by direct measurement and uptake of
      fluorescently labeled 2-D-deoxyglucose. At sacrifice, serum triglyceride levels
      and abdominal fat-pad weight were measured to assess obesity state. Adipokine
      levels were measured within abdominal fat of tumor-bearing mice. RESULTS: Mice
      fed the HFD displayed increased body weight, visceral fat, and serum leptin and
      triglycerides. All mice developed tumors; OE33 EAC cells in HFD mice displayed
      increased growth rates, proliferation, and metabolic activity relative to tumors
      of EAC in control diet mice. Adipokine expression in the abdominal fat revealed
      distinct changes associated with the HFD and increased body weight. CONCLUSIONS:
      Ad libitum feeding of the HFD was correlated with more-proliferative EAC tumors
      in vivo. This phenotype was associated with alterations to secreted adipokines,
      representing a potential mechanism for our observations. Further studies are
      necessary to explore findings, as they have potential to improve treatment of
      EAC.

PMID- 25595378
TI  - Hybrid approach to the comprehensive stage II operation in a subset of single
      ventricle variants.
AB  - OBJECTIVE: The objective of a hybrid approach to staged palliation of single
      ventricle anomalies is designed to minimize the trauma of the first stage.
      However, the second stage is a complex procedure that may negate the advantages
      of the first stage. We sought to devise a "hybrid" approach to the second stage
      when aortic outflow is expected to remain unobstructed. METHODS: The procedure
      involves a simple incision into the main pulmonary artery, dilation/stenting of
      the ductal continuation, formation of a stented baffle between the branch
      pulmonary arteries' orifices, and a bidirectional Glenn connection. It avoids
      dissection of the distal arch and ductal continuation and obviates the need for a
      Damus-Kaye-Stansel connection. We carried out this procedure in 2 patients, one
      with unbalanced atrioventricular canal and the other with mitral atresia.
      RESULTS: Both patients underwent an uncomplicated operative procedure. Both
      patients were successfully weaned from the ventilator, with no clinically evident
      neurologic injury. The first patient died of complications related to thrombosis
      of the left pulmonary artery before initiation of anticoagulation. The second
      patient is alive and well 1 year postoperation with no obstruction to either
      systemic or pulmonary flow and no baffle leak and good right ventricle function.
      CONCLUSIONS: This hybrid comprehensive stage II operation appears feasible and
      technically simpler than the conventional comprehensive stage II procedure. It is
      applicable to a subset of single-ventricle cases in which aortic outflow is
      anticipated to remain unobstructed. We recommend early postoperative
      anticoagulation to avoid early left pulmonary artery thrombosis.

PMID- 25595380
TI  - WITHDRAWN: Medicine without teamwork: A deadly sin or a common practice?
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25595379
TI  - Resection of thymoma should include nodal sampling.
AB  - OBJECTIVE: Thymoma is best treated by surgical resection; however, no clear
      guidelines have been created regarding lymph node sampling at the time of
      resection. Additionally, the prognostic implications of nodal metastases are
      unclear. The aim of this study was to analyze the prognostic implications of
      nodal metastases in thymoma. METHODS: The Surveillance, Epidemiology, and End
      Results database was queried for patients who underwent surgical resection of
      thymoma with documented pathologic examination of lymph nodes. The impact of
      nodal status on survival and thymoma staging was examined. RESULTS: We identified
      442 patients who underwent thymoma resection with pathologic evaluation of 1 or
      more lymph nodes. A median of 2 nodes were sampled per patient. Fifty-nine
      patients (59 of 442, 13.3%) had >= 1 positive node. Patients with positive nodes
      were younger and had smaller tumors than node-negative patients. Median survival
      in the node-positive patients was 98 months, compared with 144 months in node
      negative patients (P = .013). In multivariable analysis, the presence of positive
      nodes had a significant, independent, adverse impact on survival (hazard ratio
      1.945, 95% confidence interval 1.296-2.919, P = .001). The presence of nodal
      metastases resulted in a change in classification to a higher stage in 80% of
      patients, the majority from Masaoka-Koga stage III to stage IV. CONCLUSIONS:
      Nodal status seems to be an important prognostic factor in patients with thymoma.
      Until the prognostic significance of nodal metastases is better understood,
      surgical therapy for thymoma should include sampling of regional lymph nodes.

PMID- 25595382
TI  - Obesity surgery and Ramadan: a prospective analysis of nutritional intake, hunger
      and satiety and adaptive behaviours during fasting.
AB  - BACKGROUND: Fasting for religious or lifestyle reasons poses a challenge to
      people who have undergone bariatric surgery. A total fast (abstaining from all
      forms of nourishment including liquids) during long summer days puts these
      patients at risk of dehydration and poor calorie and nutrient intake. METHODS: We
      undertook telephone surveys of 24-h food recall, hunger and satiety scores,
      medication use, adverse symptoms and depression scores on a fasting day in
      Ramadan and a non-fasting day subsequently. RESULTS: We studied 207 participants
      (166 women) who had undergone sleeve gastrectomy. The mean (standard error) age
      was 35.2 (0.7) years. Men and women consumed 20.4 % (P = 0.018) and 16.9 % (P <
      0.001) fewer calories and 44.8 % (P < 0.001) and 32.4 % (P < 0.001) less protein
      during fasting, respectively. There was no significant difference in the intake
      of fluids or incidence of adverse gastrointestinal, hypoglycaemic and
      sympathoadrenal symptoms. Of participants on pharmacotherapy, 89.5 % took their
      prescribed medications; 86.3 % made no changes to the doses, but 80.4 % changed
      the timing of the medications. Both women and men reported feeling less hungry
      and a preference for savoury foods during Ramadan. There was no difference in
      depression and work impairment scores. CONCLUSIONS: Fasting was well tolerated in
      persons who had undergone sleeve gastrectomy. It may be advisable to raise
      awareness about dietary protein intake and managing medications appropriately
      during fasting.

PMID- 25595381
TI  - Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile
      of two human cell lines, THP-1 and HepG2.
AB  - BACKGROUND: Iron nanoparticles (FeNPs) have attracted increasing attention over
      the past two decades owing to their promising application as biomedical agents.
      However, to ensure safe application, their potential nanotoxicity should be
      carefully and thoroughly evaluated. Studies on the effects of FeNPs on cells at
      the transcriptomic level will be helpful for identifying any potential
      nanotoxicity of FeNPs and providing valuable mechanistic insights into various
      FeNPs-induced nanotoxicities. RESULTS: This study investigated the effects of an
      11-nm dimercaptosuccinic acid-coated magnetite nanoparticle on the gene
      expression profiles of two human cell lines, THP-1 and HepG2. It was found that
      the expression of hundreds of genes was significantly changed by a 24-h treatment
      with the nanoparticles at two doses, 50 MUg/mL and 100 MUg/mL, in the two cell
      types. By identifying the differentially expressed genes and annotating their
      functions, this study characterized the general and cell-specific effects of the
      nanoparticles on two cell types at the gene, biological process and pathway
      levels. At these doses, the overall effects of the nanoparticle on the THP-1
      cells were the induction of various responses and repression of protein
      translation, but in the HepG2 cells, the main effects were the promotion of cell
      metabolism, growth and mobility. In combination with a previous study, this study
      also characterized the common genes, biological processes and pathways affected
      by the nanoparticle in two human and mouse cell lines and identified Id3 as a
      nanotoxicity biomarker of the nanoparticle. CONCLUSION: The studied FeNPs exerted
      significant effects on the gene expression profiles of human cells. These effects
      were highly dependent on the innate biological functions of cells, i.e., the cell
      types. However, cells can also show some cell type-independent effects such as
      repression of Id3 expression. Id3 can be used as a nanotoxicity biomarker for
      iron nanoparticles.

PMID- 25595383
TI  - Trends in Weight Regain Following Roux-en-Y Gastric Bypass (RYGB) Bariatric
      Surgery.
AB  - BACKGROUND: The primary purpose of this study was to assess weight loss and
      occurrence of weight regain among patients who underwent Roux-en-Y gastric bypass
      (RYGB) using categorical analysis. METHODS: Study participants were selected from
      patients who underwent RYGB from a single institution. Participants (n = 300,
      mean procedure age = 45.6 +/- 9.9) completed surveys for self-reported
      preoperative weight, current weight, and subsequent weights over postoperative
      years. Measured weights and confirmed procedure dates were acquired from patient
      medical records. Mean preoperative weight and BMI were 140.8 kg +/- 32.1 and 49.7
      +/- 9.9, respectively, and mean years since surgery was 6.9 +/- 4.9. Study
      subjects were mostly Caucasian (56.7 %) and female (80.3 %). Participants were
      stratified a priori into four cohorts based on percent of weight loss at 1 year,
      <25 % (n = 39), 25-30 % (n = 51), 30-35 % (n = 73), and >35 % (n = 113). General
      linear model analyses were conducted to assess the effect of year one weight loss
      on percent weight regain. RESULTS: The mean weight regain for all patients was
      23.4 % of maximum weight loss. Using categorical analysis, mean weight regain in
      the <25, 25-30, 30-35, and >35 % weight loss cohorts was 29.1, 21.9, 20.9, and
      23.8 %, respectively. Excessive weight regain, defined as >=25 % of total lost
      weight, occurred in 37 % of patients. CONCLUSION: Weight gain is a common
      complication following RYGB surgery. Despite the percentage of weight loss over
      the first year, all cohort patient groups regained on average between 21 and 29 %
      of lost weight. Excessive weight gain was experienced by over one third of
      patients. Greater initial absolute weight loss leads to more successful long-term
      weight outcomes.

PMID- 25595384
TI  - Vitamin and Mineral Deficiencies After Biliopancreatic Diversion and
      Biliopancreatic Diversion with Duodenal Switch--the Rule Rather than the
      Exception.
AB  - INTRODUCTION: Malabsorptive bariatric procedures, like the biliopancreatic
      diversion (BPD) and BPD with duodenal switch (BPD/DS), have excellent results in
      terms of weight loss. However, these malabsorptive techniques are associated with
      severe malnutrition and vitamin deficiencies. The aim of this study was to
      evaluate the vitamin and mineral status after BPD and BPD/DS in the long term.
      METHODS: All patients who underwent BPD or BPD/DS were selected and invited for
      an additional follow-up (FU) visit, including blood sampling for vitamin and
      mineral levels. RESULTS: Forty patients completed the blood sampling with a
      median FU of 42 (range 12-90) months. At that time, all patients used some kind
      of supplementation. However, 93 % of all patients were diagnosed with a
      deficiency. There were no significant differences in mean serum level vitamins
      and minerals between BPD and BPD/DS. Forty-three per cent of the patients were
      anaemic, and 40 % had an iron deficiency (ID). High deficiency rates for fat
      soluble vitamins were present: vitamin A in 28 %, vitamin D in 60 %, vitamin E in
      10 % and vitamin K in 60 % of the patients. Hypervitaminosis was found in 43 % of
      the patients for vitamin B1 and in 50 % for vitamin B6. CONCLUSION: High numbers
      of vitamin and mineral deficiencies were found after BPD and BPD/DS despite
      vitamin supplementation. Anaemia, ID and deficiencies for fat-soluble vitamins
      are frequently diagnosed. Repeated monitoring is necessary to detect deficiencies
      at an early stage. Taking all of this into consideration, a stringent
      multivitamin supplementation regimen should be implemented after malabsorptive
      procedures.

PMID- 25595385
TI  - Characterization of different carbon nanotubes for the development of a
      mucoadhesive drug delivery system for intravesical treatment of bladder cancer.
AB  - In order to increase the effectiveness of therapeutics for bladder carcinoma
      (BCa) treatment, alternative strategies for intravesical applications are needed.
      The use of carbon nanotubes (CNTs) as basis for a multifunctional drug
      transporter is a promising possibility to combine traditional chemotherapeutics
      with innovative therapeutic agents such as antisense oligodeoxynucleotides or
      small interfering RNA. In the current study four CNT types varying in length and
      diameter (CNT-1, CNT-2, CNT-3, CNT-4) were synthesized and then characterized
      with different spectroscopic techniques. Compared to the pristine CNT-1 and CNT
      3, the shortened CNT-2 and CNT-4 exhibited more defects and lower aspect ratios.
      To analyze their mucoadhesive properties, CNTs were exposed to mouse bladders ex
      vivo by using Franz diffusion cells. All four tested CNT types were able to
      adhere to the urothelium with a mean covering area of 5-10%. In vitro studies on
      UM-UC-3 and EJ28 BCa cells were conducted to evaluate the toxic potential of
      these CNTs. Viability and cytotoxicity assays revealed that the shortened CNT-2
      and CNT-4 induced stronger inhibitory effects on BCa cells than CNT-1 and CNT-3.
      In conclusion, CNT-1 and CNT-3 showed the most promising properties for further
      optimization of a multifunctional drug transporter. 

PMID- 25595386
TI  - Epidermal growth factor receptor-targeted immunoliposomes for delivery of
      celecoxib to cancer cells.
AB  - Cyclooxygenase-2 (COX-2) is highly expressed in many different cancers.
      Therefore, the inhibition of the COX-2 pathway by a selective COX-2 inhibitor,
      celecoxib (CLX), may be an alternative strategy for cancer prevention and
      therapy. Liposomal drug delivery systems can be used to increase the therapeutic
      efficacy of CLX while minimizing its side effects. Previous studies have reported
      the encapsulation of CLX within the non-targeted long circulating liposomes and
      functional effect of these formulations against colorectal cancer cell lines.
      However, the selectivity and internalization of CLX-loaded liposomes can further
      be improved by grafting targeting ligands on their surface. Cetuximab (anti
      epidermal growth factor receptor - EGFR - monoclonal antibody) is a promising
      targeting ligand since EGFR is highly expressed in a wide range of solid tumors.
      The aim of this study was to develop EGFR-targeted immunoliposomes for enhancing
      the delivery of CLX to cancer cells and to evaluate the functional effects of
      these liposomes in cancer cell lines. EGFR-targeted ILs, having an average size
      of 120nm, could encapsulate 40% of the CLX, while providing a sustained drug
      release profile. Cell association studies have also shown that the immunoliposome
      uptake was higher in EGFR-overexpressing cells compared to the non-targeted
      liposomes. In addition, the CLX-loaded-anti-EGFR immunoliposomes were
      significantly more toxic compared to the non-targeted ones in cancer cells with
      EGFR-overexpression but not in the cells with low EGFR expression, regardless of
      their COX-2 expression status. Thus, selective targeting of CLX with anti-EGFR
      immunoliposomes appears to be a promising strategy for therapy of tumors that
      overexpress EGFR.

PMID- 25595387
TI  - In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability
      class determination: Investigation of the single-pass vs. the Doluisio
      experimental approaches.
AB  - Intestinal drug permeability has been recognized as a critical determinant of the
      fraction dose absorbed, with direct influence on bioavailability, bioequivalence
      and biowaiver. The purpose of this research was to compare intestinal
      permeability values obtained by two different intestinal rat perfusion methods:
      the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop)
      rat perfusion method. A list of 15 model drugs with different permeability
      characteristics (low, moderate, and high, as well as passively and actively
      absorbed) was constructed. We assessed the rat intestinal permeability of these
      15 model drugs in both SPIP and the Doluisio methods, and evaluated the
      correlation between them. We then evaluated the ability of each of these methods
      to predict the fraction dose absorbed (Fabs) in humans, and to assign the correct
      BCS permeability class membership. Excellent correlation was obtained between the
      two experimental methods (r(2)=0.93). An excellent correlation was also shown
      between literature Fabs values and the predictions made by both rat perfusion
      techniques. Similar BCS permeability class membership was designated by
      literature data and by both SPIP and Doluisio methods for all compounds. In
      conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method
      are both equally useful for obtaining intestinal permeability values that can be
      used for Fabs prediction and BCS classification. 

PMID- 25595388
TI  - Measuring drug saturation solubility in thin polymer films: use of a thin
      acceptor layer.
AB  - The saturation solubility of scopolamine base in two pressure sensitive adhesive
      DURO-TAKs has been determined using the 5-layer laminate technique. The acceptor
      layer had a thickness of less than 25 MUm to promote a rapid partitioning
      equilibrium. With DURO-TAK 87-2510 the saturation solubility is 5.2 +/- 0.6% w/w
      when measured after 7 days. With DURO-TAK 87-4098 the saturation solubility is
      slightly higher, 7.9 +/- 0.7% w/w after 7 days. These values remained constant up
      to approximately 30 days' experimental time. In both cases the acceptor was free
      of crystalline material at the end of the experiment. This strongly suggests that
      that equilibrium had been reached between the saturated solution in the acceptor
      layer and the crystalline drug still present in the donor layer. The addition of
      light liquid paraffin to the acceptor produced a solubilizing effect with 87-4098
      but not 87-2510. We recommend some experimental conditions that we consider to be
      necessary to achieve a reliable and accurate result with this technique. If
      performed correctly, it can give a feasible result.

PMID- 25595389
TI  - First in vivo evaluation of particulate nasal dry powder vaccine formulations
      containing ovalbumin in mice.
AB  - In this study three different dry powder vaccine formulations containing the
      model antigen ovalbumin were evaluated for their immune effects after nasal
      administration to C57Bl/6 mice in an adoptive cell transfer model. The
      formulations were chitosan nanoparticles in a mannitol matrix, chitosan
      microparticles and agarose nanoparticles in a mannitol matrix. Dry powder
      administration to mice was well tolerated and did not result in any adverse
      reactions. No translocation of the dry powder formulations to the lung could be
      detected. The local cellular immune response in the cervical lymph nodes was
      modest and only for the chitosan microparticles and the agarose nanoparticles was
      there a significant difference compared to s.c. injection of ovalbumin in alum.
      No humoral response could be measured after nasal administration. The results
      provide some evidence that nasal administration of dry powder formulations can
      stimulate an immune response, but the response was modest. This is probably due
      to a low antigen dose and low immunogenicity of the formulations. Further studies
      will aim at enhancing the antigen load and improving adjuvant activity. 

PMID- 25595390
TI  - Organic fraction of municipal solid waste as a suitable feedstock for the
      production of lipid by oleaginous yeast Cryptococcus aerius.
AB  - The detoxified pre-hydrolysate and enzymatic hydrolysate of OFMSW were used as
      substrates for lipid production by Cryptococcus aerius. Factorial experimental
      designs were employed for the optimization of dilute acid pre-hydrolysis,
      detoxification by over-liming, enzymatic hydrolysis, and lipid production. OFMSW
      pre-hydrolysis with 3% H2SO4 for 45 min was found to be the optimal treatment,
      resulted in total sugar concentration of 65.5 g/L (32.8% yield, based on grams of
      total reducing sugar per gram of OFMSW). The optimal detoxification conditions of
      the pre-hydrolysate by over-liming was incubation at 30  degrees C and pH 11 for
      24h, resulted in the reduction of total nitrogen, total phenolic compounds, and
      furans by 51.3%, 45.1%, and 100%, respectively. The residual solid was subjected
      to enzymatic hydrolysis, and the highest sugar concentration of 30.5 g/L was
      obtained. At optimal conditions, the yeast cultivation on the detoxified pre
      hydrolysate and enzymatic hydrolysate resulted in the lipid production of 3.9 g/L
      (12.8% yield, based on g lipid per g consumed sugar) and 4.3g/L (17.1% yield,
      based on g lipid per g consumed sugar), respectively. The elemental analysis
      showed the presence of heavy metals including iron (925 mg/l), zinc (59 mg/l),
      lead (4.7 mg/l), and nickel (3.5mg/l) in the pre-hydrolysate, which were
      significantly reduced by the over-liming detoxification.

PMID- 25595391
TI  - Anaerobic digestibility of beef hooves with swine manure or slaughterhouse
      sludge.
AB  - Anaerobic digestion is an effective method for treating animal by-products,
      generating at the same time green energy as methane (CH4). However, the methods
      and mechanisms involved in anaerobic digestion of alpha-keratin wastes like hair,
      nails, horns and hooves are still not clear. In this study we investigated the
      feasibility of anaerobically co-digesting ground beef hooves in the presence of
      swine manure or slaughterhouse sludge at 25  degrees C using eight 42-L Plexiglas
      lab-scale digesters. Our results showed addition of beef hooves statistically
      significantly increased the rate of CH4 production with swine manure, but only
      increased it slightly with slaughterhouse sludge. After 90-day digestion, 73% of
      beef hoof material added to the swine manure-inoculated digesters had been
      converted into CH4, which was significantly higher than the 45% level achieved in
      the slaughterhouse sludge inoculated digesters. BODIPY-Fluorescent casein
      staining detected proteolytic bacteria in all digesters with and without added
      beef hooves, and their relative abundances corresponded to the rate of
      methanogenesis of the digesters with the different inocula. Fluorescence in situ
      hybridization in combination with BODIPY-Fluorescent casein staining identified
      most proteolytic bacteria as members of genus Alkaliphilus in the subfamily
      Clostridiaceae 2 of family Clostridiaceae. They thus appear to be the bacteria
      mainly responsible for digestion of beef hooves.

PMID- 25595392
TI  - Economic and environmental optimization of waste treatment.
AB  - This article presents the new systems engineering optimization model, OptiWaste,
      which incorporates a life cycle assessment (LCA) methodology and captures
      important characteristics of waste management systems. As part of the
      optimization, the model identifies the most attractive waste management options.
      The model renders it possible to apply different optimization objectives such as
      minimizing costs or greenhouse gas emissions or to prioritize several objectives
      given different weights. A simple illustrative case is analysed, covering
      alternative treatments of one tonne of residual household waste: incineration of
      the full amount or sorting out organic waste for biogas production for either
      combined heat and power generation or as fuel in vehicles. The case study
      illustrates that the optimal solution depends on the objective and assumptions
      regarding the background system--illustrated with different assumptions regarding
      displaced electricity production. The article shows that it is feasible to
      combine LCA methodology with optimization. Furthermore, it highlights the need
      for including the integrated waste and energy system into the model.

PMID- 25595393
TI  - [Treatment of coma in diabetic ketoacidosis].

PMID- 25595395
TI  - Practice recommendations for pain assessment by self-report with African American
      older adults.
AB  - Despite decades of education and clinical practice guidelines underscoring
      disparities in pain management, pain continues to be inadequately managed in
      older African American adults as a result of patient, provider, and systems
      factors. Critical factors influencing pain assessment in older African American
      adults has not been extensively examined, contributing to a lack of data to
      inform health care providers' knowledge on culturally-responsive pain assessment
      in older African Americans. Assessing pain in older African Americans is unique
      because differences in language, cultural beliefs, and practices moderate how
      they report and express pain. This paper presents an overview of patient-provider
      factors that affect pain assessment in older African Americans with a focus on
      this population's unique cultural beliefs and practices. Recommendations for best
      practices for performance of a culturally-responsive pain assessment with older
      African Americans are provided. 

PMID- 25595396
TI  - Cilostazol and freedom from amputation after lower extremity revascularization.
AB  - OBJECTIVE: Cilostazol, an antiplatelet agent with vasodilating properties, has
      not been well evaluated in conjunction lower extremity revascularization (LER).
      We evaluated the association between cilostazol and limb salvage after
      endovascular or open surgery for LER. METHODS: Patients aged >=65 years
      undergoing LER were identified from 2007 to 2008 Medicare Provider Analysis and
      Review and Carrier files using International Classification of Diseases-9 Edition
      Clinical Modification and Current Procedural Terminology-4 codes. Covariates
      included demographics, comorbidities, and disease severity. Use of cilostazol was
      identified using National Drug Codes and Part D files. Outcomes were compared
      using chi(2) and Kaplan-Meier analyses and Cox regression. RESULTS: We identified
      22,954 patients undergoing LER: 8128 (35.4%) with claudication, 3056 (13.3%) with
      rest pain, and 11,770 (51.3%) with ulceration/gangrene. Among them, 1999 patients
      (8.7%) used cilostazol before LER. More patients received endovascular (14,353)
      than open (8601) procedures. Cilostazol users had fewer amputations than nonusers
      at 30 days (7.8% vs 13.4%), 90 days (10.7% vs 18.0%), and 1 year (14.8% vs 24.0%;
      P < .0001 for all). Cox proportional hazards regression with adjustment for age,
      gender, race, comorbidities, type of procedure, and atherosclerosis severity
      showed noncilostazol users were more likely to undergo amputation <=1 year after
      surgery (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.02-1.29; P =
      .02). Subgroup analyses using Cox proportional hazards models adjusted for age,
      gender, and comorbidities demonstrated significantly improved 1-year amputation
      free survival for patients with renal failure (HR, 1.61; 95% CI, 1.28-2.02; P <
      .001) and diabetes (HR, 1.61; 95% CI, 1.36-1.92; P < .001) who were taking
      cilostazol. CONCLUSIONS: In patients undergoing LER, cilostazol use was
      associated with improved 1-year freedom from amputation. Patients with renal
      failure and diabetes also demonstrated a significant benefit from taking
      cilostazol. Further studies are needed to evaluate the benefits of cilostazol
      after LER.

PMID- 25595397
TI  - Cost analysis of negative-pressure wound therapy with instillation for wound bed
      preparation preceding split-thickness skin grafts for massive (>100 cm(2))
      chronic venous leg ulcers.
AB  - OBJECTIVE: Massive (>=100 cm(2)) venous leg ulcers (VLUs) demonstrate very low
      closure rates with standard compression therapy and are costly to manage.
      Negative-pressure wound therapy (NPWT), followed by a split-thickness skin graft
      (STSG), can be a cost-effective alternative to this standard care. We performed a
      cost analysis of these two treatments. METHODS: A retrospective review was
      performed of 10 ulcers treated with surgical debridement, 7 days of inpatient
      NPWT with topical antiseptic instillation (NPWTi), and STSG, with 4 additional
      days of inpatient NPWT bolster over the graft. Independent medical cost
      estimators were used to compare the cost of this treatment protocol with standard
      outpatient compression therapy. RESULTS: The average length of time ulcers were
      present before patients entered the study was 38 months (range, 3-120 months).
      Eight of 10 patients had complete VLU closure by 6 months after NPWTi with STSG.
      The 6-month costs of the proposed treatment protocol and standard twice-weekly
      compression therapy were estimated to be $27,000 and $28,000, respectively.
      CONCLUSIONS: NPWTi with STSG treatment is more effective for closure of massive
      VLUs at 6 months than that reported for standard compression therapy. Further,
      the cost of the proposed treatment protocol is comparable with standard
      compression therapy.

PMID- 25595398
TI  - Early versus late experience in fenestrated endovascular repair for abdominal
      aortic aneurysm.
AB  - OBJECTIVE: The objective of this study was to evaluate operative results and 1
      year outcomes in early vs late experience after fenestrated endovascular aortic
      repair. METHODS: All patients treated in Malmo, Sweden, and in Lille, France,
      with fenestrated endovascular repair for abdominal aortic aneurysm were
      prospectively enrolled in a computerized database. Early experience was defined
      as the first 50 patients treated at each center. Data from early and late
      experience were retrospectively analyzed and compared for differences in
      operative results and 1-year outcomes. RESULTS: Early experience covered 4.7
      years in Malmo and 4.5 years in Lille; late experience covered 5.6 years in Malmo
      and 3.7 years in Lille. A total of 288 patients were included. In the later
      phase, stent graft configuration was more complex because of increased number of
      fenestrations/scallops incorporated in the graft design (2.7 +/- 0.8 vs 3.2 +/-
      0.7; P < .001). Despite this, volume of contrast material and radiation time
      decreased by 27% and 20%, respectively, whereas procedure time remained
      unchanged. At 1 year, a trend toward decreasing abdominal aortic aneurysm
      diameter was observed in the late group, but no differences were found in
      mortality, endoleaks, or target vessel patency between the groups. CONCLUSIONS:
      With increasing experience, fenestrated endovascular aneurysm repair design has
      become more complicated, with more visceral vessels targeted for better proximal
      seal, while operative risk still remains low. Simultaneously, radiation time and
      volume of contrast material have been reduced, with possible long-term benefits
      for the patient.

PMID- 25595399
TI  - Routine use of ultrasound guidance in femoral arterial access for peripheral
      vascular intervention decreases groin hematoma rates.
AB  - BACKGROUND: Use of fluoroscopy and bone landmarks to guide percutaneous common
      femoral artery (CFA) access has decreased access site complications compared with
      palpation alone. However, only limited case series have examined the benefits of
      ultrasound to guide CFA access during peripheral vascular intervention (PVI). We
      evaluated the effect of routine vs selective use of ultrasound guidance (UG) on
      groin hematoma rates after PVI. METHODS: The Vascular Study Group of New England
      database (2010-2014) was queried to identify the complication of postprocedural
      groin hematoma after 7359 PVIs performed through CFA access. Hematoma (including
      pseudoaneurysms) was defined as minor (requiring compression or observation),
      moderate (requiring transfusion or thrombin injection), and major (requiring
      operation). Both procedure-level and interventionalist-level analyses were
      performed. Multivariable Poisson regression models were used to compare hematoma
      rates of interventionalists based on routine (>=80% of PVIs) and selective (<80%)
      utilization of UG in the adjusted overall sample and in multiple subgroups.
      RESULTS: The overall postprocedural groin hematoma rate after PVI was 4.5%, and
      the rate of combined moderate and major hematoma was 0.8%. Among 114
      interventionalists with >=10 PVI procedures, routine and selective UG was used by
      31 (27%) and 83 (73%) interventionalists, respectively. Routine UG was protective
      against hematoma (rate ratio [RR], 0.62; 95% confidence interval [CI], 0.46-0.84;
      P < .01). Subgroup analysis revealed that routine UG was also protective against
      hematoma under the following circumstances: age >80 years (RR, 0.47; 95% CI, 0.27
      0.85; P = .01), body mass index >=30 (RR, 0.51; 95% CI, 0.29-0.90; P = .02), and
      sheath size >6F (RR, 0.43; 95% CI, 0.23-0.79; P < .01). CONCLUSIONS: Routine UG
      may potentially protect against the complication of hematoma for both modifiable
      and nonmodifiable patient and procedural characteristics. Encouraging routine UG
      is a feasible quality improvement opportunity to decrease patient morbidity after
      PVI.

PMID- 25595400
TI  - Developing a complex endovascular fenestrated and branched aortic program.
AB  - In 2008, the top priority in our division's 5-year strategic plan was "to become
      an internationally recognized center of excellence for the endovascular treatment
      of complex aortic pathology extending from the aortic valve to the external iliac
      artery." Five components were identified as "most critical" to achieve this
      strategic priority: (1) training at centers of excellence in complex endovascular
      repair; (2) industry partnership to improve access to developing technologies;
      (3) a fully integrated team approach with one leader involved in all steps of all
      cases; (4) prospective data collection; and (5) development and implementation of
      a physician-sponsored investigational device exemption for juxtarenal, pararenal,
      and thoracoabdominal aneurysms. We have now performed 49 repairs (16 commercially
      manufactured devices, 33 physician-modified devices) for 3 common iliac, 20
      juxtarenal, 9 pararenal, and 17 thoracoabdominal aneurysms, using 142
      fenestrations, branches, and scallops. All patients had complete 30-day follow-up
      for calculation of 30-day events. Kaplan-Meier analysis was used to calculate 1
      year events. In 5 years, we developed a successful complex endovascular aortic
      program that uses fenestrated/branched repair techniques. A focused team
      strategic planning approach to program development is an effective way for
      vascular surgery divisions to gain experience and expertise with new complex
      technologies while ensuring acceptable patient outcomes.

PMID- 25595401
TI  - Results of combined vascular reconstruction and free flap transfer for limb
      salvage in patients with critical limb ischemia.
AB  - OBJECTIVE: Combined vascular reconstruction and free flap transfer has been
      established in centers as a feasible therapeutic option in cases with critical
      limb ischemia (CLI) and large tissue defects otherwise destined for major
      amputation. However, the number of patients treated with this combined approach
      is limited, and data regarding long-term follow-up and functional outcome are
      scarce. We therefore report our 10-year experience in free flap transplantation
      after vascular reconstruction as a last attempt for limb salvage, with special
      emphasis of complication rate, limb salvage, and postoperative mobility. METHODS:
      CLI patients undergoing combined vascular reconstruction and consequent free flap
      transfer from 2003 to 2013 were retrospectively observed. Of 80 cases in total,
      patients with traumatic and oncologic indications were excluded; 33 (mean age, 66
      years; range, 51-82 years) of these cases were performed for limb salvage and
      were included in this study. Long-term follow-up was possible in 32 of 33
      patients (mean, 58 months; range, 2-126 months). RESULTS: Thirty-three patients
      were analyzed. We performed arterial revascularization with 9 arteriovenous
      loops, 23 bypass grafts (10 popliteal-pedal, 9 femoral-crural, and 4 femoral
      popliteal), and 1 venous interposition graft. For defect coverage, tissue
      transfer was comprised of six different flap entities (10 latissimus dorsi, 2
      gracilis, 1 anterior lateral thigh, 7 rectus abdominis, 11 radialis, and 2
      greater omentum flaps). Complications occurred in 16 of 33 patients (49%). Early
      complications included eight acute occlusions of arterial reconstructions; major
      bleedings were seen in eight patients as well. There were two flap losses and one
      major amputation in the early postoperative period. No in-hospital deaths were
      observed. Late results revealed a limb salvage rate of 87% after 1 year and 83%
      after 5 years. Amputation-free survival was 87% after 1 year and 75% after 5
      years. Overall survival was 100% and 87% after 1 year and 5 years, respectively.
      Follow-up showed 42% of patients with no limitations in ambulation, 54% with
      maintained preoperative ambulatory status, and one bedridden patient.
      CONCLUSIONS: The combined approach for limb salvage in CLI patients is associated
      with excellent results in limb salvage and functional outcome in patients who
      would otherwise be candidates for major amputation, despite an initially elevated
      complication rate. The option of combined revascularization with free tissue
      transfer should be evaluated in all mobile patients with CLI, large tissue
      defects, and exposed tendon or bone structures before major amputation. However,
      further studies are required to support these results.

PMID- 25595402
TI  - Clinical presentation, comorbidities, and age but not female gender predict
      survival after endovascular repair of abdominal aortic aneurysm.
AB  - OBJECTIVE: The objective was to study associations between clinical variables,
      demographic factors, and outcome after endovascular aneurysm repair (EVAR) of
      abdominal aortic aneurysm (AAA). METHODS: Data of consecutive patients who
      underwent EVAR between 1997 and 2011 at a tertiary center were analyzed.
      Comorbidity scores stratified patients into low/normal-risk (score <= 10) or high
      risk categories (score > 10). The primary end point was mortality; secondary end
      points were morbidities, reinterventions, conversions, and ruptures. RESULTS: The
      study included 934 patients, 117 women (13%) and 817 men (87%) (mean age, 76 +/-
      7.3 years; range, 51-99 years). There were 870 (93%) asymptomatic, 36 (3.9%)
      symptomatic, and 28 (3.0%) ruptured AAAs. The 30-day mortality was 1.4% (13 of
      934), 1.0% (9 of 870) for asymptomatic patients, 2.8% (1 of 36) for patients with
      symptomatic AAAs, and 11% (3 of 28) for patients with ruptured AAAs (P = .004).
      Clinical presentation with symptoms or rupture was associated with more
      complications (P = .02), reinterventions (P = .003), and a lower 5-year survival
      (P = .04). Association between surgical risk, female gender, age, and outcome was
      studied in 870 asymptomatic patients. Both 30-day mortality and complication
      rates were higher for high-risk vs low/normal-risk patients (2.3% vs 0.2%, P =
      .003; 15% vs 10%, P = .04); reintervention rates were equivalent (3.8% vs 4.4%; P
      = .67). The 30-day mortality and complication rates were similar in women and men
      (2.8% vs 0.8%, P = .09; 17% vs 11%, P = .11), but reintervention rate was higher
      in women (8.5% vs 3.5%; P = .02). Follow-up averaged 3.8 years (1 month-13.5
      years). In asymptomatic patients, 5-year survival was 74% for low/normal-risk
      patients and 54% for high-risk patients (P < .001); both had similar rates of
      freedom from complications (65% vs 63%; P = .24), reinterventions (71% vs 75%; P
      = .36), or rupture (99.3% vs 99.7%; P = .42). Women had more complications (47%
      vs 34%; P = .04) and reinterventions than men did (39% vs 26%; P = .02); freedom
      from rupture was the same (100% vs 99.3%; P = .30). There were eight ruptures,
      all in asymptomatic patients. In multivariate analysis, high surgical risk and
      age were associated with all-cause mortality (P < .001); female gender was
      associated with complications and reinterventions (P < .05) but not mortality.
      CONCLUSIONS: Clinical presentation predicts early mortality and complications,
      age predicts both early and late mortalities after EVAR. Although women had an
      increased rate of complications and reinterventions, women did not have
      significantly higher mortality than men.

PMID- 25595403
TI  - Endovascular rescue after inadvertent false lumen stent graft implantation.
AB  - We report a case of a 58-year-old patient with a complicated type B aortic
      dissection who developed acute visceral malperfusion after placement of a
      thoracic aortic stent graft from the true to the false lumen. He underwent an
      urgent endovascular revision that involved septal fenestration and distal
      extension of the stent graft into the true lumen. 

PMID- 25595405
TI  - The anatomist Andreas Vesalius at 500 years old.

PMID- 25595404
TI  - Prospective controlled pilot study of arteriovenous fistula placement using the
      novel Optiflow device.
AB  - OBJECTIVE: Arteriovenous fistula (AVF) maturation failure remains a significant
      problem with reported early failure rates around 50%. Suboptimal hemodynamics,
      variable surgical skills, and technique dependency are widely believed to
      contribute to AVF nonmaturation. The Optiflow (Bioconnect Systems, Ambler, Pa) is
      a novel anastomotic device placed in situ that has potential for improving
      hemodynamics and standardizing AVF placement. We report results from a
      prospective nonrandomized controlled pilot study designed to investigate the
      safety and performance of the Optiflow. METHODS: Forty-one participants underwent
      AVF formation using either a 3-mm or 4-mm Optiflow and 39 matched control
      participants underwent AVF formation using the standard technique at two sites.
      Patients were observed for 90 days after AVF placement. The primary end point was
      unassisted maturation, which was defined as an outflow vein with a diameter >=5
      mm and blood flow >=500 mL/min measured by Doppler ultrasound. The secondary
      performance end point was unassisted patency, and the primary safety end point
      was freedom from device-related serious adverse events. RESULTS: Unassisted
      maturation rates at 14, 42, and 90 days were 76%, 72%, and 68%, respectively, for
      the Optiflow group and 67%, 68%, and 76%, respectively, in the control group (P =
      .38, .69, and .47 at 14, 42, and 90 days). There was a trend to earlier
      maturation (assessed at 14 days) in the 4-mm Optiflow group compared with the
      control group (P = .059). There were no device-related serious adverse events.
      CONCLUSIONS: Maturation results for both the Optiflow and control groups were
      highly favorable compared with historical assisted maturation rates of
      approximately 50%. The Optiflow appears to be safe and effective in the placement
      of AVFs, with high maturation rates.

PMID- 25595406
TI  - Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth
      factor gene attenuates restenosis in rabbit balloon-injured artery.
AB  - OBJECTIVE: New and efficient strategies to protect endothelium or to enhance
      endothelial regrowth are important for treatment of restenosis after percutaneous
      transluminal angioplasty. Magnetic DNA microspheres are used to accelerate
      vascular endothelial growth factor (VEGF) re-endothelialization and to attenuate
      intimal hyperplasia in balloon-injured artery. This study aimed to assess DNA
      gelatin magnetic nanospheres containing VEGF expression plasmids in vascular
      restenosis attenuation. METHODS: Ninety-six rabbits underwent balloon injury and
      were randomly divided for gene transfer with naked VEGF plasmids (NAK group),
      magnetic VEGF microspheres (MIC group), and LacZ (CON group: naked LacZ plasmid
      and LacZ nanosphere subgroups). Serum and tissue VEGF levels were measured. Also,
      the ratios of intima area to media area were determined to assess neointima
      formation. RESULTS: Microsphere gene delivery through the artery by a magnet
      resulted in VEGF overexpression in transfected arterial segments. Tissue VEGF
      integral optical densities were significantly increased in MIC rabbits compared
      with NAK animals. Serum VEGF was below detection in all animals. X-Gal staining
      showed higher transfection efficiency in the CON group. The impact of neointimal
      thickening was evaluated by light microscopy as the ratio of intima area to media
      area in cross sections. Significant differences in the ratio of intima area to
      media area were obtained between the NAK group (0.12 +/- 0.02, 0.41 +/- 0.03,
      0.61 +/- 0.05, and 0.72 +/- 0.04 at 1, 2, 3, and 4 weeks, respectively) and the
      MIC group (0.06 +/- 0.03, 0.20 +/- 0.05, 0.25 +/- 0.04, and 0.26 +/- 0.03 at 1,
      2, 3, and 4 weeks, respectively) at 2, 3, and 4 weeks (P < .05). CONCLUSIONS:
      Intra-arterial VEGF gene delivery by magnetic microspheres significantly
      increased DNA stability, transfection efficiency, and targeting specificity,
      resulting in exogenous VEGF overexpression and attenuated intimal hyperplasia in
      balloon-injured artery.

PMID- 25595407
TI  - Evolution of gender-related differences in outcomes from two decades of
      endovascular aneurysm repair.
AB  - OBJECTIVE: Women have been under-represented in trials that set guidelines for
      the management of aortic aneurysms. Several studies reported inferior outcomes in
      women compared with men after endovascular aneurysm repair (EVAR). We
      investigated the relationship between gender and outcomes after EVAR. METHODS: A
      total of 1380 consecutive patients underwent elective EVAR from 1992 to 2012.
      Baseline, intraoperative, and postoperative variables by gender were analyzed
      from a prospective database. RESULTS: The cohort comprised 214 women (15.5%) and
      1166 men (84.5%). Women were older than men at repair (77.8 vs 74.5 years, P <
      .001) and had less cardiac disease (P = .005). They had shorter (19.8 +/- 12.9 vs
      26.3 +/- 14.7 mm; P < .001) more angulated aortic necks (38.8 degrees  +/- 16.1
      degrees  vs 31.2 degrees  +/- 14.7 degrees ; P < .001) and fewer iliac aneurysms
      (P = .002). Women had more arterial reconstructions (iliac conduits, P = .006;
      thrombolysis and thrombectomy, P = .013; patch angioplasty, P < .001;
      endarterectomy, P < .001), more perioperative complications (16.9% vs 9.1%; P =
      .001), and more in-hospital days (4.1 vs 3.4 days; P = .029). Perioperative
      mortality was equivalent (women: 2% vs men: 2.3%; P = .73). Mean follow-up was
      30.9 months. Women and men experienced equivalent aneurysm-related deaths and
      overall survival. Survival curve analysis showed endoleaks were more likely to
      develop in women than men (P = .005); however, there was no difference in rates
      of arterial reinterventions required for each gender during the follow-up period.
      CONCLUSIONS: Female gender is associated with more periprocedural complications,
      adjunctive arterial procedures, and increased endoleaks but does not affect long
      term reinterventions or survival. Further studies are warranted to elucidate the
      effect of gender on outcomes. These data should be considered when selecting EVAR
      for men and women.

PMID- 25595408
TI  - Elevated serum cystatin C level is an independent predictor of contrast-induced
      nephropathy and adverse outcomes in patients with peripheral artery disease
      undergoing endovascular therapy.
AB  - OBJECTIVE: The aim of this study was to investigate the association of serum
      cystatin C levels with contrast-induced nephropathy (CIN) and adverse clinical
      events in patients with peripheral artery disease (PAD). METHODS: A total of 240
      PAD patients who received endovascular therapy were included in this
      retrospective analysis. Serial serum levels of creatinine and cystatin C before
      and within 48 hours of endovascular therapy were evaluated for the incidence of
      CIN. The relationship between serum cystatin C levels and the incidence of major
      adverse events, defined as a composite of all-cause death, myocardial infarction,
      stroke, amputation, and target vessel revascularization, was investigated.
      RESULTS: The incidence of CIN increased from 1.7% to 27.9%, depending on the
      quartile of baseline cystatin C level. Baseline serum cystatin C level (area
      under the curve of the receiver operating characteristic curve, 0.757; 95%
      confidence interval [CI], 0.696-0.735) predicted the incidence of CIN better than
      baseline serum creatinine level (area under the curve, 0.629; 95% CI, 0.563
      0.691; P < .001). An elevated baseline cystatin C level was an independent
      predictor of CIN (hazard ratio, 14.37; 95% CI, 4.11-50.19; P < .001) and major
      adverse events in patients with PAD (hazard ratio, 2.57; 95% CI, 1.28-5.17; P =
      .008). CONCLUSIONS: We found elevated baseline cystatin C level to be an
      independent risk factor for CIN and a predictor of all-cause mortality and major
      adverse events in patients with PAD undergoing endovascular therapy.

PMID- 25595409
TI  - Cilostazol improves high glucose-induced impaired angiogenesis in human
      endothelial progenitor cells and vascular endothelial cells as well as enhances
      vasculoangiogenesis in hyperglycemic mice mediated by the adenosine monophosphate
      activated protein kinase pathway.
AB  - OBJECTIVE: Cilostazol is an antiplatelet agent with vasodilatory effects that
      works by increasing intracellular concentrations of cyclic adenosine
      monophosphate (cAMP). This study investigated the effects of cilostazol in
      preventing high glucose (HG)-induced impaired angiogenesis and examined the
      potential mechanisms involving activation of AMP-activated protein kinase (AMPK).
      METHODS: Assays for colony formation, adhesion, proliferation, migration, and
      vascular tube formation were used to determine the effect of cilostazol in HG
      treated endothelial progenitor cells (EPCs) or human umbilical vein endothelial
      cells (HUVECs). Animal-based assays were performed in hyperglycemic ICR mice
      undergoing hind limb ischemia. An immnunoblotting assay was used to identify the
      expression and activation of signaling molecules in vitro and in vivo. RESULTS:
      Cilostazol treatment significantly restored endothelial function in EPCs and
      HUVECs through activation of AMPK/acetyl-coenzyme A carboxylase (ACC)-dependent
      pathways and cAMP/protein kinase A (PKA)-dependent pathways. Recovery of blood
      flow in the ischemic hind limb and the population of circulating CD34(+) cells
      were significantly improved in cilostazol-treated mice, and these effects were
      abolished by local AMPK knockdown. Cilostazol increased the phosphorylation of
      AMPK/ACC and Akt/endothelial nitric oxide synthase signaling molecules in
      parallel with or downstream of the cAMP/PKA-dependent signaling pathway in vitro
      and in vivo. CONCLUSIONS: Cilostazol prevents HG-induced endothelial dysfunction
      in EPCs and HUVECs and enhances angiogenesis in hyperglycemic mice by
      interactions with a broad signaling network, including activation of AMPK/ACC and
      probably cAMP/PKA pathways.

PMID- 25595410
TI  - Expression and biochemical characterization of a type I methionine aminopeptidase
      of Plasmodium vivax.
AB  - Methionine aminopeptidases (MetAPs), ubiquitous enzymes that play an important
      role in nascent protein maturation, have been recognized as attractive targets
      for the development of drugs against pathogenic protozoa including Plasmodium
      spp. Here, we characterized partial biochemical properties of a type I MetAP of
      Plasmodium vivax (PvMetAP1). PvMetAP1 had the typical amino acid residues
      essential for metal binding and substrate binding sites, which are well conserved
      in the type I MetAP family enzymes. Recombinant PvMetAP1 showed activity in a
      broad range of neutral pHs, with optimum activity at pH 7.5. PvMetAP1 was stable
      under neutral and alkaline pHs, but was relatively unstable under acidic
      conditions. PvMetAP1 activity was highly increased in the presence of Mn(2+), and
      was effectively inhibited by a metal chelator, EDTA. Fumagillin and
      aminopeptidase inhibitors, amastatin and bestatin, also showed an inhibitory
      effect on PvMetAP1. The enzyme had a highly specific hydrolytic activity for N
      terminal methionine. These results collectively suggest that PvMetAP1 belongs to
      the family of type I MetAPs and may play a pivotal role for the maintenance of P.
      vivax physiology by mediating protein maturation and processing of the parasite. 

PMID- 25595411
TI  - [Quality of life after primary parotidectomy for benign tumor].
AB  - INTRODUCTION: Parotidectomy is commonly performed for various indications,
      including benign tumors of the parotid region. Esthetic or functional sequels of
      various importance and lasting effects may occur, as after any surgical
      procedure. These disorders may impact the patient's quality of life. The authors
      retrospectively evaluated the long-term outcome of patients having undergone
      conservative primary parotidectomy for a benign tumor, with a minimum follow-up
      of 10 years. PATIENTS AND METHODS: A hundred and twenty-six superficial
      conservative primary or secondary parotidectomies were performed during 5 years,
      94 (74.6%) of which for benign tumors. A flap of the sternocleidomastoid muscle
      (SCM) was inserted between the skin and facial nerve branches to prevent Frey's
      syndrome and alleviate surgical site depression according to some criteria.
      Questionnaires were completed at least 10 years after surgery. RESULTS: The data
      of 53 patients was analyzed. 88.7% of patients had undergone a superficial
      parotidectomy and 11.3% a total one. The average histological tumor size was 3.3
      cm (2.6 to 6.3 cm). The tumors were distributed as follows: pleomorphic adenoma
      in 79.4% of patients, cystadenolymphoma in 15.1%, oncocytoma in 3.7%, and basal
      cell adenoma in 1.8%. Twenty-six SCM flaps (49.1%) were performed. No patient
      presented with facial paresis or facial paralysis at the end of the study. The
      average follow-up was 10.4 years (10-11 years). Overall, social, psychological,
      and professional implications were reported by 7.5% of patients, and in 1.8% of
      cases the impact was significant. The use of a SCM flap seemed to prevent Frey's
      syndrome (Fischer test P=0.00001) and improved cosmetic results (Fisher test
      P<0.00001). DISCUSSION: Conservative parotidectomy for primary benign tumors has
      a limited impact on the quality of life in the long run. This impact concerned
      7.4% of patients. There was a significant impact in 2% of patients. We recommend
      filling the surgical site to improve functional and esthetic results and decrease
      long-term effects on the patient's quality of life.

PMID- 25595412
TI  - [Evaluation of the impact of an educational intervention on the knowledge and
      nursing care of the external ventricular drain].

PMID- 25595413
TI  - Immediate changes in pressure pain sensitivity after thoracic spinal manipulative
      therapy in patients with subacromial impingement syndrome: A randomized
      controlled study.
AB  - BACKGROUND: Thoracic SMT can improve symptoms in patients with subacromial
      impingement syndrome. However, at this time the mechanisms of SMT are not well
      established. It is possible that changes in pain sensitivity may occur following
      SMT. OBJECTIVES: To assess the immediate pain response in patients with shoulder
      pain following thoracic spinal manipulative therapy (SMT) using pressure pain
      threshold (PPT), and to assess the relationship of change in pain sensitivity to
      patient-rated outcomes of pain and function following treatment. DESIGN:
      Randomized Controlled Study. METHODS: Subjects with unilateral subacromial
      impingement syndrome (n = 45) were randomly assigned to receive treatment with
      thoracic SMT or sham thoracic SMT. PPT was measured at the painful shoulder
      (deltoid) and unaffected regions (contralateral deltoid and bilateral lower
      trapezius areas) immediately pre- and post-treatment. Patient-rated outcomes were
      pain (numeric pain rating scale - NPRS), function (Pennsylvania Shoulder Score -
      Penn), and global rating of change (GROC). RESULTS: There were no significant
      differences between groups in pre-to post-treatment changes in PPT (p >= 0.583)
      nor were there significant changes in PPT within either group (p >= 0.372)
      following treatment. NPRS, Penn and GROC improved across both groups (p < 0.001),
      but there were no differences between the groups (p >= 0.574). CONCLUSION: There
      were no differences in pressure pain sensitivity between participants receiving
      thoracic SMT versus sham thoracic SMT. Both groups had improved patient-rated
      pain and function within 24-48 h of treatment, but there was no difference in
      outcomes between the groups.

PMID- 25595414
TI  - Multi-phase cycle coding for SSVEP based brain-computer interfaces.
AB  - BACKGROUND: Brain-computer interfaces (BCIs) based on Steady State Visual Evoked
      Potential (SSVEP) have attracted more and more attentions for their short time
      response and high information transfer rate (ITR). The use of a high stimulation
      frequency (from 30 Hz to 40 Hz) is more comfortable for users and can avoid the
      amplitude-frequency problem, but the number of available phases for stimulation
      source is limited. To circumvent this deficiency, a novel protocol named Multi
      Phase Cycle Coding (MPCC) for SSVEP-based BCIs was proposed in the present study.
      METHODS: In MPCC, each target is coded by a block word that includes a series of
      cyclic codewords, and each block word is corresponding to a certain flickering
      visual stimulus, which is a combination of multiple phases from an available
      phase set and flickers at single frequency. The methods of generating block code
      and extracting phase were presented and experiments were performed to investigate
      the feasibility of MPCC. RESULTS: The optimal stimulation frequency was subject
      specific, and the optimal duration was longer than 0.5 s. The BCI system with
      MPCC could achieve average discrimination accuracy 93.51 +/- 5.62% and
      information transfer rate 33.77 +/- 8.67%. CONCLUSIONS: The MPCC has the error
      correction ability, can effectively increase the encoded targets and improve the
      performance of the system. Therefore, the MPCC is promising for practical BCIs.

PMID- 25595415
TI  - Oxidative stress and decreased thiol level in patients with migraine: cross
      sectional study.
AB  - Although migraine is a neurological disorder known since long, its
      physiopathology remains unclear. Recent studies suggest that migraine is
      associated with oxidative stress; however, they report divergent results. The aim
      of the present study was to evaluate total antioxidant status (TAS), total
      oxidant status (TOS), oxidative stress index (OSI), and serum thiol level in
      migraine patients with or without aura. The study group consisted of 141 migraine
      patients. The control group included 70 healthy subjects. TAS, TOS, OSI were
      evaluated using a method developed by Erel. Serum thiol level was measured using
      the Hu method. No difference was found in TAS, TOS, OSI between the patients and
      controls. The level of thiol was significantly lower in patients than in
      controls. Negative correlations were detected between thiol level and Migraine
      Disability Assessment score in patients. Although TAS, TOS, and OSI were similar
      to those of the control group, serum thiol level, an important marker of
      antioxidant capacity, was significantly lower in migraines compared with
      controls, and caused more serious disability. Novel treatment approaches may be
      developed based on these data, and compounds containing thiol, such as alpha
      lipoic acid and N-acetyl cysteine, may be used in prophylaxis.

PMID- 25595416
TI  - Myocardial ischaemia and post-systolic shortening.
AB  - The assessment of regional wall motion is useful to identify myocardial ischaemia
      because wall motion abnormalities occur relatively upstream in the ischaemic
      cascade. Echocardiography is widely used for this, but the subjectivity of visual
      observation may hamper accurate evaluation. The analysis of myocardial velocity
      and strain by tissue Doppler and speckle tracking echocardiography has allowed
      the quantitative assessment of regional wall motion and facilitated the detection
      of subtle myocardial deformation that is difficult to identify by conventional
      methods, such as post-systolic shortening (PSS). PSS is defined as myocardial
      shortening that occurs after end-systole (or aortic valve closure), and it is
      observed in the myocardium with regional contractile dysfunction. In experimental
      and clinical studies, it has been reported that the assessment of PSS is superior
      to that of conventional parameters such as wall thickening or peak systolic
      strain in detecting acute ischaemia and diagnosing coronary artery disease.
      Moreover, it has recently been found that PSS remains after recovery from brief
      ischaemia despite the rapid recovery of peak systolic strain. The assessment of
      PSS allows after-the-fact recognition of myocardial ischaemic insults and is
      expected to be used for ischaemic memory imaging. In this review, the usefulness
      of the assessment of PSS for the diagnosis of acute ischaemia and ischaemic
      memory is demonstrated, and issues that need to be resolved for the widespread
      use of this assessment in the echocardiographic laboratory are discussed. 

PMID- 25595417
TI  - High-dose atorvastatin is superior to moderate-dose simvastatin in preventing
      peripheral arterial disease.
AB  - OBJECTIVES: To study whether high-dose versus usual-dose statin treatment reduces
      the incidence of peripheral artery disease (PAD) and what is the effect of high
      dose statin treatment on cardiovascular disease (CVD) outcome in patients with
      PAD. METHODS AND RESULTS: In the Incremental Decrease in End Points Through
      Aggressive Lipid Lowering trial, 8888 post-myocardial infarction patients were
      randomised to high-dose or usual-dose statin therapy (atorvastatin 80 mg/day vs
      simvastatin 20-40 mg/day). We investigated the effect of high-dose versus usual
      dose statins on the pre-specified outcome PAD incidence, and additionally
      performed a posthoc analysis of the efficacy of high-dose statins in reducing CVD
      risk among patients with PAD. During a median follow-up of 4.8 years, 94 patients
      (2.2%) receiving atorvastatin and 135 patients (3.2%) receiving simvastatin
      developed PAD (HR=0.70, 95% CI 0.53 to 0.91; p=0.007). The risk of major coronary
      events was almost twofold higher in patients with PAD at baseline, but was no
      longer significant after adjusting for the adverse cardiovascular risk profile.
      In PAD patients, major coronary events occurred in fewer patients in the
      atorvastatin group (14.4%) than in the simvastatin group (20.1%), but the
      difference did not reach statistical significance. (HR=0.68, 95% CI 0.41 to 1.11;
      p=0.13). Atorvastatin treatment significantly reduced overall cardiovascular
      (p=0.046) and coronary events (p=0.004), and coronary revascularisation (p=0.007)
      in these patients. CONCLUSIONS: High-dose statin therapy with atorvastatin
      significantly reduced the incidence of PAD compared with usual-dose statin
      therapy with simvastatin. Patients with a history of PAD at baseline were at
      higher risk of future coronary events and this risk was reduced by high-dose
      atorvastatin treatment. TRIAL REGISTRATION NUMBER: NCT00159835 (URL:
      http://clinicaltrials.gov/show/NCT00159835).

PMID- 25595418
TI  - Helminth control in kennels: is the combination of milbemycin oxime and
      praziquantel a right choice?
AB  - BACKGROUND: Kennel dogs are at the high risk of infections with intestinal and
      extra-intestinal helminths. Therefore, regular parasitological surveillance,
      appropriate treatment strategies and high quality standard of hygiene are
      required to guarantee the health and welfare of kennel dogs. The aim of the
      present study was to evaluate the efficacy of helminth control in kennels using
      different broad-spectrum anthelmintics that are routinely used in canine
      veterinary practice. Particular attention was given to the field efficacy and
      ease-of-use of each product. METHODS: The study was conducted in 3 public kennels
      in the Campania region (southern Italy). Eighteen boxes from each of the three
      kennels were selected for treatment based on faecal egg counts (FECs) at Day -30.
      The treatments were conducted using tablets containing combinations of: i)
      milbemycin oxime and praziquantel (Milbemax(r)); ii) pyrantel embonate, febantel
      and praziquantel (Drontal Plus Flavour(r)), and; iii) pyrantel pamoate, oxantel
      pamoate and praziquantel (Nemex(r) POP). All dogs were treated on Day 0 and
      sampled on Days 0, 7, 14 and 21 for copromicroscopic analyses. The FLOTAC dual
      technique on pooled samples was used with efficacy determined by reduction in
      FECs. RESULTS: At Day -30 intestinal nematodes (hookworms, Toxocara, Trichuris)
      and cestodes (Dypilidium caninum) were found. Milbemax(r) showed 100% efficacy
      against all the helminths in all the kennels. Drontal Plus Flavour(r) was 100%
      effective against hookworms in all the kennels but gave lower efficacy against T.
      canis (range=97.1-100%) and T. vulpis (range=95.6-100%). Nemex(r) POP was also
      100% effective against hookworms in all kennels but less effective against T.
      canis (range=95.7-100%) and T. vulpis (range=95.7-100%). All three drugs were
      100% effective against D.caninum. CONCLUSIONS: Milbemax(r)was fully effective
      against all the helminthes and was palatable and ease-of-use for all the dogs. It
      is the optimum choice for the treatment and prevention of helminth infections in
      kennel dogs under field conditions.

PMID- 25595419
TI  - Successful trans-apical aortic valve implantation for a high risk patient with
      aortic stenosis using a new second-generation TAVI device - J-Valve system.
AB  - Transcatheter aortic valve implantation (TAVI) has evolved as a routine procedure
      to treat selected high-risk patients with severe aortic stenosis. The new J-Valve
      prosthesis is designed for antegrade transapical implantation, it is
      characterized by a porcine aortic prosthesis attaching to a self-expandable
      Nitinol stent. The key feature of the device are three U-shape anatomically
      oriented devices - "graspers" which could facilitate intuitive 'self-positioning'
      valve implantation. Hereby, we report a successful case of trans-apical TAVI in
      an elderly high-risk patient with severe aortic stenosis using J-Valve system.

PMID- 25595420
TI  - Measurement and modeling on hydrodynamic forces and deformation of an air bubble
      approaching a solid sphere in liquids.
AB  - The interaction between bubbles and solid surfaces is central to a broad range of
      industrial and biological processes. Various experimental techniques have been
      developed to measure the interactions of bubbles approaching solids in a liquid.
      A main challenge is to accurately and reliably control the relative motion over a
      wide range of hydrodynamic conditions and at the same time to determine the
      interaction forces, bubble-solid separation and bubble deformation. Existing
      experimental methods are able to focus only on one of the aspects of this
      problem, mostly for bubbles and particles with characteristic dimensions either
      below 100 MUm or above 1 cm. As a result, either the interfacial deformations are
      measured directly with the forces being inferred from a model, or the forces are
      measured directly with the deformations to be deduced from the theory. The
      recently developed integrated thin film drainage apparatus (ITFDA) filled the gap
      of intermediate bubble/particle size ranges that are commonly encountered in
      mineral and oil recovery applications. Equipped with side-view digital cameras
      along with a bimorph cantilever as force sensor and speaker diaphragm as the
      driver for bubble to approach a solid sphere, the ITFDA has the capacity to
      measure simultaneously and independently the forces and interfacial deformations
      as a bubble approaches a solid sphere in a liquid. Coupled with the thin liquid
      film drainage modeling, the ITFDA measurement allows the critical role of surface
      tension, fluid viscosity and bubble approach speed in determining bubble
      deformation (profile) and hydrodynamic forces to be elucidated. Here we compare
      the available methods of studying bubble-solid interactions and demonstrate
      unique features and advantages of the ITFDA for measuring both forces and bubble
      deformations in systems of Reynolds numbers as high as 10. The consistency and
      accuracy of such measurement are tested against the well established Stokes
      Reynolds-Young-Laplace model. The potential to use the design principles of the
      ITFDA for fundamental and developmental research is demonstrated.

PMID- 25595422
TI  - Forced to remember: when memory is biased by salient information.
AB  - The last decades have seen a rapid growing in the attempt to understand the key
      factors involved in the internal memory representation of the external world.
      Visual salience have been found to provide a major contribution in predicting the
      probability for an item/object embedded in a complex setting (i.e., a natural
      scene) to be encoded and then remembered later on. Here I review the existing
      literature highlighting the impact of perceptual- (based on low-level sensory
      features) and semantics-related salience (based on high-level knowledge) on short
      term memory representation, along with the neural mechanisms underpinning the
      interplay between these factors. The available evidence reveal that both
      perceptual- and semantics-related factors affect attention selection mechanisms
      during the encoding of natural scenes. Biasing internal memory representation,
      both perceptual and semantics factors increase the probability to remember high-
      to the detriment of low-saliency items. The available evidence also highlight an
      interplay between these factors, with a reduced impact of perceptual-related
      salience in biasing memory representation as a function of the increasing
      availability of semantics-related salient information. The neural mechanisms
      underpinning this interplay involve the activation of different portions of the
      frontoparietal attention control network. Ventral regions support the assignment
      of selection/encoding priorities based on high-level semantics, while the
      involvement of dorsal regions reflects priorities assignment based on low-level
      sensory features.

PMID- 25595421
TI  - Neurotensin immunolabeling relates to sexually-motivated song and other social
      behaviors in male European starlings (Sturnus vulgaris).
AB  - The brain regions involved in vocal communication are well described for some
      species, including songbirds, but less is known about the neural mechanisms
      underlying motivational aspects of communication. Mesolimbic dopaminergic
      projections from the ventral tegmental area (VTA) are central to mediating
      motivated behaviors. In songbirds, VTA provides dopaminergic innervation to brain
      regions associated with motivation and social behavior that are also involved in
      sexually-motivated song production. Neurotensin (NT) is a neuropeptide that
      strongly modulates dopamine activity, co-localizes with dopamine in VTA, and is
      found in regions where dopaminergic cells project from VTA. Yet, little is known
      about how NT contributes to vocal communication or other motivated behaviors. We
      examined the relationships between sexually-motivated song produced by male
      European starlings (Sturnus vulgaris) and NT immunolabeling in brain regions
      involved in social behavior and motivation. Additionally, we observed
      relationships between NT labeling, non-vocal courtship behaviors (another measure
      of sexual motivation), and agonistic behavior to begin to understand NT's role in
      socially-motivated behaviors. NT labeling in VTA, lateral septum, and bed nucleus
      of the stria terminalis correlated with sexually-motivated singing and non-vocal
      courtship behaviors. NT labeling in VTA, lateral septum, medial preoptic nucleus,
      and periaqueductal gray was associated with agonistic behavior. This study is the
      first to suggest NT's involvement in song, and one of the few to implicate NT in
      social behaviors more generally. Additionally, our results are consistent with
      the idea that distinct patterns of neuropeptide activity in brain areas involved
      in social behavior and motivation underlie differentially motivated behaviors. 

PMID- 25595424
TI  - Wave intensity analysis in air-filled flexible vessels.
AB  - Wave intensity analysis (WIA) is an analytical technique generally used to
      investigate the propagation of waves in the cardiovascular system. Despite its
      increasing usage in the cardiovascular system, to our knowledge WIA has never
      been applied to the respiratory system. Given the analogies between arteries and
      airways (i.e. fluid flow in flexible vessels), the aim of this work is to test
      the applicability of WIA with gas flow instead of liquid flow. The models
      employed in this study are similar to earlier studies used for arterial
      investigations. Simultaneous pressure (P) and velocity (U) measurements were
      initially made in a single tube and then in several flexible tubes connected in
      series. Wave speed was calculated using the foot-to-foot method (cf), which was
      used to separate analytically the measured P and U waveforms into their forward
      and backward components. Further, the data were used to calculate wave intensity,
      which was also separated into its forward and backward components. Although the
      measured wave speed was relatively high, the results showed that the onsets and
      the nature of reflections (compression/expansion) derived with WIA, corresponded
      well to those anticipated using the theory of waves in liquid-filled elastic
      tubes. On average the difference between the experimental and theoretical arrival
      time of reflection was 6.1% and 3.6% for the single vessel and multivessel
      experiment, respectively. The results suggest that WIA can provide relatively
      accurate information on reflections in air-filled flexible tubes, warranting
      further studies to explore the full potential of this technique in the
      respiratory system.

PMID- 25595423
TI  - Modeling falls in Parkinson's disease: Slow gait, freezing episodes and falls in
      rats with extensive striatal dopamine loss.
AB  - Falls in patients with Parkinson's disease (PD) are a major and levodopa
      unresponsive source of morbidity. We previously described an animal model of
      falls resulting from impairments in attentional-motor interactions. Reproducing
      the multisystem dopaminergic-cholinergic cell loss in patients with a history for
      falls, partial loss of striatal dopamine innervation interacted with loss of
      forebrain cholinergic neurons to generate falls that was hypothesized to reflect
      impairments in the attentional control of gait and balance and the sequencing of
      complex movements [1]. As clinical evidence also indicates that basal ganglia
      dopamine (DA) loss per se is associated with severe discoordination and thus a
      greater risk for falls, here we demonstrate that relatively extensive striatal DA
      loss, in contrast to the lack of effects of smaller, dorsal striatal DA losses
      and sham lesions, increased falls and slips and caused slowing while traversing
      dynamic surfaces. Falls in large DA rats were associated specifically with
      spontaneous or slip-triggered stoppages of forward movement. Collectively, the
      evidence suggests that low motivation or vigor for movement in general, and for
      initiating corrective movements in particular, are major sources for falls in
      rats with large DA losses. Falls are a result of complex cognitive-motor
      interactions, and rats with large DA losses model the impact of a propensity for
      freezing of gait when traversing dynamic surfaces. 

PMID- 25595425
TI  - How tibiofemoral alignment and contact locations affect predictions of medial and
      lateral tibiofemoral contact forces.
AB  - Understanding degeneration of biological and prosthetic knee joints requires
      knowledge of the in-vivo loading environment during activities of daily living.
      Musculoskeletal models can estimate medial/lateral tibiofemoral compartment
      contact forces, yet anthropometric differences between individuals make accurate
      predictions challenging. We developed a full-body OpenSim musculoskeletal model
      with a knee joint that incorporates subject-specific tibiofemoral alignment (i.e.
      knee varus-valgus) and geometry (i.e. contact locations). We tested the accuracy
      of our model and determined the importance of these subject-specific parameters
      by comparing estimated to measured medial and lateral contact forces during
      walking in an individual with an instrumented knee replacement and post-operative
      genu valgum (6 degrees ). The errors in the predictions of the first peak medial
      and lateral contact force were 12.4% and 11.9%, respectively, for a model with
      subject-specific tibiofemoral alignment and contact locations determined through
      radiographic analysis, vs. 63.1% and 42.0%, respectively, for a model with
      generic parameters. We found that each degree of tibiofemoral alignment deviation
      altered the first peak medial compartment contact force by 51N (r(2)=0.99), while
      each millimeter of medial-lateral translation of the compartment contact point
      locations altered the first peak medial compartment contact force by 41N
      (r(2)=0.99). The model, available at www.simtk.org/home/med-lat-knee/, enables
      the specification of subject-specific joint alignment and compartment contact
      locations to more accurately estimate medial and lateral tibiofemoral contact
      forces in individuals with non-neutral alignment.

PMID- 25595426
TI  - TGF-beta-activated SMAD3/4 complex transcriptionally upregulates N-cadherin
      expression in non-small cell lung cancer.
AB  - OBJECTIVES: Epithelial-mesenchymal transition (EMT) is a key process in early
      stage of cancer metastasis. TGF-beta-mediated EMT is characterized by repression
      of E-cadherin and induction of N-cadherin (CDH2) in various cancers. Although
      many investigations have focused on the regulation of E-cadherin expression, the
      transcription-mediated events that directly induce N-cadherin expression in TGF
      beta-induced EMT are not fully clear. Here, we mainly focus on non-small cell
      lung cancer (NSCLC) cells, in which expression of CDH2 can be activated upon TGF
      beta stimulation, to investigate the underlying mechanisms of CDH2 expression
      regulation. MATERIALS AND METHODS: Western blot analysis, real-time quantitative
      reverse transcriptase PCR, luciferase reporter gene assays, RNA interference and
      in vivo chromatin immunoprecipitation (ChIP) assay were performed on human NSCLC
      cell lines A549 and SPC-A1. Twenty-six paired NSCLC tissues and adjacent
      noncancerous lung tissues were collected. RESULTS: Luciferase reporter assay
      revealed that a functional TGF-beta-response element was located at position 
      1078 to -891 in the CDH2 promoter region. Furthermore, in vivo ChIP experiment
      indicated that TGF-beta-activated SMAD3/4 complex was directly recruited to CDH2
      promoter region (-1078 to -891). Upon TGF-beta1 stimulation, knockdown of SMAD3
      or/and SMAD4 led to a significant reduction in CDH2 promoter activity, and
      silencing of SMAD3 or SMAD4 significantly inhibited CDH2 mRNA and protein
      expression in A549 and SPC-A1 cells. In human NSCLC tissues, SMAD3 or SMAD4 mRNA
      level was positively correlated with CDH2 mRNA level, respectively. CONCLUSIONS:
      We found that TGF-beta-activated SMAD3/4 complex may upregulate CDH2 expression
      by directly interacting with a specific SMAD-binding element in CDH2 promoter.
      Our findings provide insights into mechanisms underlying the transcriptional
      regulation of CDH2 expression in TGF-beta-induced EMT and SMADs-based therapeutic
      strategies for NSCLCs.

PMID- 25595427
TI  - Secondary nailing after external fixation for tibial shaft fracture: risk factors
      for union and infection. A 55 case series.
AB  - INTRODUCTION: Secondary intramedullary nailing (SIN) following external fixation
      (EF) of tibial shaft fracture is controversial, notably due to the infection
      risk, which is not precisely known. The present study therefore analysed a
      continuous series of tibial shaft SIN, to determine (1) infection and union
      rates, and (2) whether 1-stage SIN associated to EF ablation increased the risk
      of infection. HYPOTHESIS: Factors exist for union and onset of infection
      following tibial shaft SIN. MATERIALS AND METHODS: A retrospective series of SIN
      performed between 1998 and 2012 in over 16-year-old patients with non-pathologic
      tibial shaft fracture was analysed. EF pin site infection was an exclusion
      criterion. Fractures were graded according to AO and Gustilo classifications.
      Study parameters were: time to SIN, 1- versus 2-stage procedure, bacteriologic
      results on reaming product, post-nailing onset of infection, and time to union.
      RESULTS: Fifty-five patients (55 fractures) were included. There were 16 closed
      and 39 open fractures: 7 Gustilo type I, 26 type II and 6 type IIIA; 33 AO type
      A, 14 type B and 8 type C. Mean time to SIN was 9 +/- 9.6 weeks (range, 4 days to
      12 months). There were 23 1-stage procedures, and 32 two-stage procedures with a
      mean 12-day interval (range, 4-30 days). Twelve reaming samples were biologically
      positive without secondary infection. There were 4 septic complications (3
      abscesses, 1 osteomyelitis), and 1 aseptic non-union required re-nailing. The
      union rate was 96%. The sole factor of poor prognosis was severity of fracture
      opening. One-stage SIN did not increase infection risk. DISCUSSION: The present
      results were better than reported in the literature, where the rates of Gustilo
      IIIA and IIIB fracture and pin site infection are, however, higher. Tibial shaft
      SIN is a reliable procedure, with infection risk correlating with Gustilo type
      and time to surgery. Surgery should be early, before onset of EF pin site
      infection. A 1-stage attitude appears feasible in early SIN. LEVEL OF EVIDENCE:
      Level IV. Retrospective study type.

PMID- 25595429
TI  - Adult flatfoot.
AB  - Adult flatfoot is defined as a flattening of the medial arch of the foot in
      weight-bearing and lack of a propulsive gait. The 3 lesion levels are the
      talonavicular, tibiotarsal and midfoot joints. The subtalar joint is damaged by
      the consequent rotational defects. Clinical examination determines deformity and
      reducibility, and assesses any posterior tibialis muscle deficit, the posterior
      tibialis tendon and spring ligament being frequently subject to degenerative
      lesions. Radiographic examination in 3 incidences in weight-bearing is essential,
      to determine the principal level of deformity. Tendon (posterior tibialis tendon)
      and ligamentous lesions (spring ligament and interosseous ligament) are analyzed
      on MRI or ultrasound. In fixed deformities, CT explores for arthritic evolution
      or specific etiologies. 3D CT reconstruction can analyze bone and joint
      morphology and contribute to the planning of any osteotomy. Medical management
      associates insoles and physiotherapy. Acute painful flatfoot requires strict cast
      immobilization. Surgical treatment associates numerous combinations of
      procedures, currently under assessment for supple flatfoot: for the hindfoot:
      medial slide calcaneal osteotomy, calcaneal lengthening osteotomy, or
      arthroereisis; for the midfoot: arthrodesis on one or several rays, or first
      cuneiform or first metatarsal osteotomy; for the ankle: medial collateral
      ligament repair with tendon transfer. Fixed deformities require arthrodesis of
      one or several joint-lines in the hindfoot; for the ankle, total replacement
      after realignment of the foot, or tibiotalocalcaneal fusion or ankle and hindfoot
      fusion; and, for the midfoot, cuneonavicular or cuneometatarsal fusion. Tendinous
      procedures are often associated. Specific etiologies may need individualized
      procedures. In conclusion, adult flatfoot tends to be diagnosed and managed too
      late, with consequent impact on the ankle, the management of which is complex and
      poorly codified. 

PMID- 25595428
TI  - Evolution of slipped capital femoral epiphysis after in situ screw fixation at a
      mean 11 years' follow-up: a 222 case series.
AB  - INTRODUCTION: Slipped capital femoral epiphysis (SCFE) can lead to hip
      impingement, more or less rapidly depending on initial slippage severity and on
      surgical technique. Various surgical options are applicable, including in situ
      fixation (ISF). The aim of the present study was to look for long-term signs of
      radiological impingement in hips treated for SCFE by IFS, in order to identify a
      slip threshold beyond which impingement more regularly appears. MATERIAL AND
      METHODS: A multicenter retrospective study assessed the clinical and radiological
      evolution of patients operated on by ISF for SCFE, with a minimum 10 year's
      follow-up. Coxometric analysis of postoperative and last follow-up radiographs
      was performed. Functional outcome was assessed on Oxford hip score and
      radiographic osteoarthritis on the Tonnis classification. Alpha angle was
      measured on lateral views to highlight hip impingement. RESULTS: Two hundred and
      twenty-two hips were included, with a mean 11.2 years' follow-up. Mean age at
      diagnosis was 12.8 years. Mean preoperative Southwick angle was 38.8 degrees ,
      with 43% of hips at stage I, 42% at stage II and 15% at stage III. At latest
      follow-up, mean Oxford score was 14.86, with 88% of hips rated Tonnis 0 or I.
      Only 15 cases of impingement were diagnosed. There seemed to be a non-significant
      trend for hip impingement in SCFE exceeding 35 degrees . CONCLUSION: ISF led to
      hip impingement in moderate to severe initial epiphyseal displacement. However,
      in smaller displacement, the consequences were milder, with perfectly
      satisfactory function scores and no clinical or radiological evidence of
      impingement. The threshold seemed to be around 35 degrees  slippage, beyond which
      other surgical options than ISF should be considered. Thus, it seems reasonable
      to propose isolated ISF in SCFE<35 degrees  and to treat symptomatic impingement
      by surgery in stage II slips.

PMID- 25595430
TI  - Risk of sural nerve injury during lateral distal Achilles tendinoscopy: a cadaver
      study.
AB  - BACKGROUND: The risk of damage to cutaneous sensory nerves located near portals
      has been evaluated for both conventional arthroscopy and extra-articular
      posterior ankle endoscopy. The objective of the anatomic study reported here was
      to assess the risk of injury to the sural nerve or lateral calcaneal nerve while
      using the distal lateral portal for the Achilles tendinoscopy procedure described
      by Vega et al. in 2008. MATERIALS AND METHODS: We dissected the sural nerve and
      its branch, the lateral calcaneal nerve, of 13 human cadaver ankles in the prone
      position. We defined P as the point where the Achilles peritendon was opened
      during the distal lateral approach used for the study technique. P was adjacent
      to the lateral edge of the Achilles tendon, 2 cm proximal to the postero-superior
      edge of the calcaneal tuberosity. T was defined as the attachment site of the
      most lateral fibres of the Achilles tendon to the postero-superior edge of the
      calcaneal tuberosity. We evaluated the origin of the lateral calcaneal nerve
      relative to T and we measured the shortest distances separating P from the sural
      nerve and lateral calcaneal nerve. RESULTS: A lateral calcaneal nerve was
      identified in 10 (77%) ankles and originated a mean of 39.1mm (range, 25.0
      65.0mm) proximal to T. P was at a mean distance from the sural nerve of 12.3mm
      (range, 5.0-18.0mm) and from the lateral calcaneal nerve of 6.8mm (range, 4.0
      9.0mm). The median difference between these two distances was statistically
      significant (P=0.002). DISCUSSION: While using the distal lateral portal for
      Achilles tendinoscopy, the lateral calcaneal nerve is at greater risk for injury
      than is the sural nerve. LEVEL OF EVIDENCE: Level IV. Anatomic Study.

PMID- 25595431
TI  - Detecting inbreeding depression for reproductive traits in Iberian pigs using
      genome-wide data.
AB  - BACKGROUND: The current availability of genotypes for very large numbers of
      single nucleotide polymorphisms (SNPs) is leading to more accurate estimates of
      inbreeding coefficients and more detailed approaches for detecting inbreeding
      depression. In the present study, genome-wide information was used to detect
      inbreeding depression for two reproductive traits (total number of piglets born
      and number of piglets born alive) in an ancient strain of Iberian pigs (the
      Guadyerbas strain) that is currently under serious danger of extinction. METHODS:
      A total of 109 sows with phenotypic records were genotyped with the PorcineSNP60
      BeadChip v1. Inbreeding depression was estimated using a bivariate animal model
      in which the inbreeding coefficient was included as a covariate. We used two
      different measures of genomic inbreeding to perform the analyses: inbreeding
      estimated on a SNP-by-SNP basis and inbreeding estimated from runs of
      homozygosity. We also performed the analyses using pedigree-based inbreeding.
      RESULTS: Significant inbreeding depression was detected for both traits using all
      three measures of inbreeding. Genome-wide information allowed us to identify one
      region on chromosome 13 associated with inbreeding depression. This region spans
      from 27 to 54 Mb and overlaps with a previously detected quantitative trait locus
      and includes the inter-alpha-trypsin inhibitor gene cluster that is involved with
      embryo implantation. CONCLUSIONS: Our results highlight the value of high-density
      SNP genotyping for providing new insights on where genes causing inbreeding
      depression are located in the genome. Genomic measures of inbreeding obtained on
      a SNP-by-SNP basis or those based on the presence/absence of runs of homozygosity
      represent a suitable alternative to pedigree-based measures to detect inbreeding
      depression, and a useful tool for mapping studies. To our knowledge, this is the
      first study in domesticated animals using the SNP-by-SNP inbreeding coefficient
      to map specific regions within chromosomes associated with inbreeding depression.

PMID- 25595432
TI  - Ionic liquid assisted electrospun cellulose acetate fibers for aqueous removal of
      triclosan.
AB  - The cellulose acetate (CA) membrane prepared via electrospun was innovatively
      utilized as fiber-adsorbent for the separation of aqueous triclson (TCS). It was
      found that the presence of the room temperature ionic liquid (RTIL) in the
      precursor amplified electric force toward the CA-solution, thereby benefiting the
      formation of CA fibers. The as-spun CA fibers exhibit excellent adsorptive
      performance toward TCS, with fast adsorption kinetics, and the maximum adsorption
      capacity achieved to 797.7 mg g(-1), which established much better performance in
      contrast to conventional adsorbents. We proposed that the adsorption of TCS onto
      CA fibers was primarily facilitated by the hydrogen bonding between the abundant
      carbonyl, hydroxyl groups of CA surface, and the hydrogen atoms of phenol
      functional groups in TCS molecular. 

PMID- 25595434
TI  - Acuity-based nurse assignment and patient scheduling in oncology clinics.
AB  - The oncology clinics use different nursing care delivery models to provide
      chemotherapy treatment to cancer patients. Functional and primary care delivery
      models are the most commonly used methods in the clinics. In functional care
      delivery model, patients are scheduled for a chemotherapy appointment without
      considering availabilities of individual nurses, and nurses are assigned to
      patients according to patient acuities, nursing skill, and patient mix on a given
      day after the appointment schedule is determined. Patients might be treated by
      different nurses on different days of their treatment. In primary care delivery
      model, each patient is assigned to a primary nurse, and the patients are
      scheduled to be seen by the same nurse every time they come to the clinic for
      treatment. However, these clinics might experience high variability in daily
      nurse workload due to treatment protocols that should be followed strictly. In
      that case, part-time nurses can be utilized to share the excess workload of the
      primary nurses. The aim of this study is to develop optimization methods to
      reduce the time spent for nurse assignment and patient scheduling in oncology
      clinics that use different nursing care delivery models. For the functional
      delivery model, a multiobjective optimization model with the objectives of
      minimizing patient waiting times and nurse overtime is proposed to solve the
      nurse assignment problem. For the primary care delivery model, another
      multiobjective optimization model with the objectives of minimizing total
      overtime and total excess workload is proposed to solve the patient scheduling
      problem. Spreadsheet-based optimization tools are developed for easy
      implementation. Computational results show that the proposed models provide
      multiple nondominated solutions, which can be used to determine the optimal
      staffing levels. 

PMID- 25595433
TI  - Optimizing an HIV testing program using a system dynamics model of the continuum
      of care.
AB  - Realizing the full individual and population-wide benefits of antiretroviral
      therapy for human immunodeficiency virus (HIV) infection requires an efficient
      mechanism of HIV-related health service delivery. We developed a system dynamics
      model of the continuum of HIV care in Vancouver, Canada, which reflects key
      activities and decisions in the delivery of antiretroviral therapy, including HIV
      testing, linkage to care, and long-term retention in care and treatment. To
      measure the influence of operational interventions on population health outcomes,
      we incorporated an HIV transmission component into the model. We determined
      optimal resource allocations among targeted and routine testing programs to
      minimize new HIV infections over five years in Vancouver. Simulation scenarios
      assumed various constraints informed by the local health policy. The project was
      conducted in close collaboration with the local health care providers, Vancouver
      Coastal Health Authority and Providence Health Care. 

PMID- 25595435
TI  - Reference values for high-density lipoprotein particle size and volume by dynamic
      light scattering in a Brazilian population sample and their relationships with
      metabolic parameters.
AB  - BACKGROUND: Current data indicate that the size of high-density lipoprotein (HDL)
      may be considered an important marker for cardiovascular disease risk. We
      established reference values of mean HDL size and volume in an asymptomatic
      representative Brazilian population sample (n=590) and their associations with
      metabolic parameters by gender. METHODS: Size and volume were determined in HDL
      isolated from plasma by polyethyleneglycol precipitation of apoB-containing
      lipoproteins and measured using the dynamic light scattering (DLS) technique.
      RESULTS: Although the gender and age distributions agreed with other studies, the
      mean HDL size reference value was slightly lower than in some other populations.
      Both HDL size and volume were influenced by gender and varied according to age.
      HDL size was associated with age and HDL-C (total population); non- white
      ethnicity and CETP inversely (females); HDL-C and PLTP mass (males). On the other
      hand, HDL volume was determined only by HDL-C (total population and in both
      genders) and by PLTP mass (males). CONCLUSIONS: The reference values for mean HDL
      size and volume using the DLS technique were established in an asymptomatic and
      representative Brazilian population sample, as well as their related metabolic
      factors. HDL-C was a major determinant of HDL size and volume, which were
      differently modulated in females and in males.

PMID- 25595438
TI  - Comprehensive metabolomic profiling of type 2 diabetes.

PMID- 25595437
TI  - Overriding concerns: the role of electronic medical record-based best practice
      alerts in reducing unnecessary laboratory testing.

PMID- 25595436
TI  - Identification of potential pancreatic cancer serum markers: Increased sialyl
      Lewis X on ceruloplasmin.
AB  - Pancreatic adenocarcinoma (PDAC) usually shows an enhanced expression of sialyl
      Lewis X (sLe(x)) and related epitopes. PDAC may secrete some of the proteins
      carrying such increased sLe(x) determinant into serum, so they could be used as
      PDAC markers. Previously, we identified acute-phase proteins with increased
      sLe(x) in both PDAC and in chronic pancreatitis patients. In this study, depleted
      sera from the main acute-phase proteins has been analysed for the search of
      proteins with increased sLe(x) levels in PDAC. Sera from healthy controls,
      chronic pancreatitis and PDAC patients were depleted, electrophoresed and
      subjected to sLe(x) immunodetection. Proteins that differentially expressed
      sLe(x) in PDAC were trypsin digested and identified by LC-ESI-QTOF mass
      spectrometry. Five protein bands that differentially expressed sLe(x) in PDAC
      were identified and corresponded to seven different acute-phase proteins. Among
      them, ceruloplasmin (CP) was selected for further analysis. N-glycan sequencing
      of CP confirmed the increase of sLe(x) levels in CP in PDAC patients. Healthy
      controls, chronic pancreatitis and PDAC patients' sera were immunoprecipitated
      with anti-CP antibodies, and their sLe(x) and CP levels were analysed by western
      blot. The sLe(x)/CP ratio tended to be higher for the PDAC group, which
      altogether suggests that the sLe(x)/CP ratio could be a useful biomarker for
      PDAC. 

PMID- 25595439
TI  - Serial changes in high-sensitivity cardiac troponin, N-terminal pro-B-type
      natriuretic peptide, and heart fatty acid binding protein during exercise
      echocardiography in patients with suspected angina pectoris and normal resting
      left ventricular function.

PMID- 25595440
TI  - Clinical sensitivity and specificity of meconium fatty acid ethyl ester, ethyl
      glucuronide, and ethyl sulfate for detecting maternal drinking during pregnancy.
AB  - BACKGROUND: We investigated agreement between self-reported prenatal alcohol
      exposure (PAE) and objective meconium alcohol markers to determine the optimal
      meconium marker and threshold for identifying PAE. METHODS: Meconium fatty acid
      ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were
      quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study
      participants. Detailed PAE information was collected from women with a validated
      timeline follow-back interview. Because meconium formation begins during weeks 12
      20, maternal self-reported drinking at or beyond 19 weeks was our exposure
      variable. RESULTS: Of 107 women, 33 reported no alcohol consumption in pregnancy,
      16 stopped drinking by week 19, and 58 drank beyond 19 weeks (including 45 third
      trimester drinkers). There was moderate to substantial agreement between self
      reported PAE at >=19 weeks and meconium EtG >=30 ng/g (kappa = 0.57, 95% CI 0.41
      0.73). This biomarker and associated cutoff was superior to a 7 FAEE sum >=2
      nmol/g and all other individual and combination marker cutoffs. With meconium EtG
      >=30 ng/g as the gold standard condition and maternal self-report at >=19 weeks'
      gestation as the test condition, 82% clinical sensitivity (95% CI 71.6-92.0) and
      75% specificity (95% CI 63.2-86.8) were observed. A significant dose
      concentration relationship between self-reported drinks per drinking day and
      meconium EtG >=30 ng/g also was observed (all P < 0.01). CONCLUSIONS: Maternal
      alcohol consumption at >=19 weeks was better represented by meconium EtG >=30
      ng/g than currently used FAEE cutoffs.

PMID- 25595441
TI  - Hepatotoxicity from antituberculous therapy in the elderly: a systematic review.
AB  - BACKGROUND: Elderly persons have the highest rates of tuberculosis (TB) in the
      United States compared to all other age groups. A systematic literature review
      was conducted to determine if older age was a risk factor for hepatotoxicity
      resulting from treatment with first-line drugs used to treat active (TB) and
      latent tuberculosis (LTBI). METHODS: A systematic review of MEDLINE, Cochrane
      Controlled Trial Registry, CINAHL((r)), and Science Citation Index Expanded (from
      1970 to 2011) was performed to determine the risk of hepatotoxicity, comparing
      those over 60 with those under 60. A meta-analysis was performed using a random
      effects model along with log odds ratios and the chi-square test. FINDINGS:
      Thirty-eight studies (40,034 participants; 1208 cases of hepatotoxicity) met the
      selection criteria. For active TB, an overall mean effect of 0.277 (p = 0.024,
      95% CI: 0.037-0.517) was observed, which is equivalent to an odds ratio of 1.32
      (95% CI: 1.04-1.68). For LTBI, an overall mean effect of 1.42 (p < 0.001, 95% CI:
      0.794-2.05) was observed, which translates to an odds ratio of 4.14 (95% CI: 2.21
      7.74). INTERPRETATION: Our analysis revealed that patients older than 60 had
      significantly more risk of hepatotoxicity. These studies suggest that a gentler
      regimen of treatment for older individuals could benefit health outcomes in this
      population of TB patients and minimize risks to the public's health.

PMID- 25595442
TI  - End-stage renal disease in Japanese children: a nationwide survey during 2006
      2011.
AB  - BACKGROUND: End-stage renal disease (ESRD) in children is considered a rare, but
      serious condition. Epidemiological and demographic information on pediatric ESRD
      patients around the world is important to better understand this disease and to
      improve patient care. The Japanese Society for Pediatric Nephrology (JSPN)
      reported epidemiological and demographic data in 1998. Since then, however, there
      has been no nationwide survey on Japanese children with ESRD. METHODS: The JSPN
      conducted a cross-sectional nationwide survey in 2012 to update information on
      the incidence, primary renal disease, initial treatment modalities, and survival
      in pediatric Japanese patients with ESRD aged less than 20 years during the
      period 2006-2011. RESULTS: The average incidence of ESRD was 4.0 per million age
      related population. Congenital anomalies of the kidney and urinary tract were the
      most common cause of ESRD, present in 39.8 % of these patients. In addition, 12.2
      % had focal segmental glomerulosclerosis and 5.9 % had glomerulonephritis.
      Initial treatment modalities in patients who commenced renal replacement therapy
      (RRT) consisted of peritoneal dialysis, hemodialysis, and pre-emptive
      transplantation (Tx) in 61.7, 16.0, and 22.3 %, respectively. The Japanese RRT
      mortality rate was 18.2 deaths per 1000 person-years of observation. CONCLUSION:
      The incidence of ESRD is lower in Japanese children than in children of other
      high-income countries. Since 1998, notably, there has been a marked increase in
      pre-emptive Tx as an initial treatment modality for Japanese children with ESRD.

PMID- 25595443
TI  - Interdisciplinary collaboration in the provision of a pharmacist-led discharge
      medication reconciliation service at an Irish teaching hospital.
AB  - BACKGROUND: Medication reconciliation is a basic principle of good medicines
      management. With the establishment of the National Acute Medicines Programme in
      Ireland, medication reconciliation has been mandated for all patients at all
      transitions of care. The clinical pharmacist is widely credited as the healthcare
      professional that plays the most critical role in the provision of medication
      reconciliation services. OBJECTIVES: To determine the feasibility of the clinical
      pharmacist working with the hospital doctor, in a collaborative fashion, to
      improve the completeness and accuracy of discharge prescriptions through the
      provision of a pharmacist led discharge medication reconciliation service.
      SETTING: 243-bed acute teaching hospital of Trinity College Dublin, Ireland.
      METHOD: Cross-sectional observational study of discharge prescriptions identified
      using non-probability consecutive sampling. Discharge medication reconciliation
      was provided by the clinical pharmacist. Non-reconciliations were communicated
      verbally to the doctor, and documented in the patient's medical notes as
      appropriate. The pharmacist and/or doctor resolved the discrepancies according to
      predetermined guidelines. MAIN OUTCOME MEASURES: Number and type of discharge
      medication non-reconciliations, and acceptance of interventions made by the
      clinical pharmacist in their resolution. Number of discharge medication non
      reconciliations requiring specific input of the hospital doctor. RESULTS: In
      total, the discharge prescriptions of 224 patients, involving 2,245 medications
      were included in the study. Prescription non-reconciliation was identified for
      62.5 % (n = 140) of prescriptions and 15.8 % (n = 355) of medications, while
      communication non-reconciliation was identified for 92 % (n = 206) of
      prescriptions and 45.8 % (n = 1,029) of medications. Omission of preadmission
      medications (76.6 %, n = 272) and new medication non-reconciliations (58.5 %, n =
      602) were the most common type. Prescription non-reconciliations were fully
      resolved on 55.7 % (n = 78) of prescriptions prior to discharge; 67.9 % (n = 53)
      by the doctor, 26.9 % (n = 21) by the clinical pharmacist, and 5.2 % (n = 4) by
      the joint input of doctor and pharmacist. All communication non-reconciliations
      were resolved prior to discharge; 97.1 % (n = 200) by the pharmacist, and 2.9 %
      (n = 6) by both doctor and pharmacist. CONCLUSION: This study demonstrates how
      interdisciplinary collaboration, between the clinical pharmacist and hospital
      doctor, can improve the completeness and accuracy of discharge prescriptions
      through the provision of a pharmacist led discharge medication reconciliation
      service at an Irish teaching hospital.

PMID- 25595447
TI  - Early loss of monocanalicular silicone tubes in congenital nasolacrimal duct
      obstruction: incidence, predictors, and effect on outcome.
AB  - PURPOSE: To study predictors and implications on outcome of premature silicone
      tube-loss, a post-operative complication of monocanalicular intubation (MCI)
      performed for treatment of congenital nasolacrimal duct obstruction (CNLDO).
      METHODS: We conducted a retrospective analysis of cases of post-operative loss of
      monocanalicular silicone tubes occurring at one medical center from January 2007
      to December 2013. RESULTS: During the study period monocanclicular silicone tubes
      were lost in 24/54 eyes (44%) of 19/46 children. Multivariate regression analysis
      identified bilateral intubation as an important predictor of early tube-loss
      (r=0.54, P=0.006). Seven of eight (88%) children who had both eyes intubated
      prematurely lost their tubes compared to 12/38 (32%) children who had unilateral
      intubation (P=0.005). Treatment success was lower in eyes with early tube-loss
      (17/24 eyes, 71%) compared to eyes with full tube retention (25/30 eyes, 83%),
      however this difference was not statistically significant (P=0.333). In our
      study, treatment outcome correlated with duration of intubation (r=0.51,
      P=0.002). Surgical success was achieved in 33/39 eyes (85%) in which the tubes
      were retained at least 2 months compared to 7/15 eyes (47%) with shorter period
      of intubation (P=0.012). CONCLUSIONS: Spontaneous tube-loss is a post-operative
      complication of monocanalicular silicone intubation that can occur more
      frequently than previously reported in certain populations. Tube-loss occurring
      soon after surgery is often associated with persistent symptoms and increased
      need of reoperation.

PMID- 25595445
TI  - Molecular characterization of hap complex components responsible for methanol
      inducible gene expression in the methylotrophic yeast Candida boidinii.
AB  - We identified genes encoding components of the Hap complex, CbHAP2, CbHAP3, and
      CbHAP5, as transcription factors regulating methanol-inducible gene expression in
      the methylotrophic yeast Candida boidinii. We found that the Cbhap2Delta,
      Cbhap3Delta, and Cbhap5Delta gene-disrupted strains showed severe growth defects
      on methanol but not on glucose and nonfermentable carbon sources such as ethanol
      and glycerol. In these disruptants, the transcriptional activities of methanol
      inducible promoters were significantly decreased compared to those of the wild
      type strain, indicating that CbHap2p, CbHap3p, and CbHap5p play indispensable
      roles in methanol-inducible gene expression. Further molecular and biochemical
      analyses demonstrated that CbHap2p, CbHap3p, and CbHap5p localized to the nucleus
      and bound to the promoter regions of methanol-inducible genes regardless of the
      carbon source, and heterotrimer formation was suggested to be necessary for
      binding to DNA. Unexpectedly, distinct from Saccharomyces cerevisiae, the Hap
      complex functioned in methanol-specific induction rather than glucose
      derepression in C. boidinii. Our results shed light on a novel function of the
      Hap complex in methanol-inducible gene expression in methylotrophic yeasts. 

PMID- 25595446
TI  - A FACS-optimized screen identifies regulators of genome stability in Candida
      albicans.
AB  - Loss of heterozygosity (LOH) plays important roles in genome dynamics, notably,
      during tumorigenesis. In the fungal pathogen Candida albicans, LOH contributes to
      the acquisition of antifungal resistance. In order to investigate the mechanisms
      that regulate LOH in C. albicans, we have established a novel method combining an
      artificial heterozygous locus harboring the blue fluorescent protein and green
      fluorescent protein markers and flow cytometry to detect LOH events at the single
      cell level. Using this fluorescence-based method, we have confirmed that elevated
      temperature, treatment with methyl methanesulfonate, and inactivation of the Mec1
      DNA damage checkpoint kinase triggered an increase in the frequency of LOH.
      Taking advantage of this system, we have searched for C. albicans genes whose
      overexpression triggered an increase in LOH and identified four candidates, some
      of which are known regulators of genome dynamics with human homologues
      contributing to cancer progression. Hence, the approach presented here will allow
      the implementation of new screens to identify genes that are important for genome
      stability in C. albicans and more generally in eukaryotic cells. 

PMID- 25595444
TI  - Identification and characterization of LFD-2, a predicted fringe protein required
      for membrane integrity during cell fusion in neurospora crassa.
AB  - The molecular mechanisms of membrane merger during somatic cell fusion in
      eukaryotic species are poorly understood. In the filamentous fungus Neurospora
      crassa, somatic cell fusion occurs between genetically identical germinated
      asexual spores (germlings) and between hyphae to form the interconnected network
      characteristic of a filamentous fungal colony. In N. crassa, two proteins have
      been identified to function at the step of membrane fusion during somatic cell
      fusion: PRM1 and LFD-1. The absence of either one of these two proteins results
      in an increase of germling pairs arrested during cell fusion with tightly
      appressed plasma membranes and an increase in the frequency of cell lysis of
      adhered germlings. The level of cell lysis in DeltaPrm1 or Deltalfd-1 germlings
      is dependent on the extracellular calcium concentration. An available
      transcriptional profile data set was used to identify genes encoding predicted
      transmembrane proteins that showed reduced expression levels in germlings
      cultured in the absence of extracellular calcium. From these analyses, we
      identified a mutant (lfd-2, for late fusion defect-2) that showed a calcium
      dependent cell lysis phenotype. lfd-2 encodes a protein with a Fringe domain and
      showed endoplasmic reticulum and Golgi membrane localization. The deletion of an
      additional gene predicted to encode a low-affinity calcium transporter, fig1,
      also resulted in a strain that showed a calcium-dependent cell lysis phenotype.
      Genetic analyses showed that LFD-2 and FIG1 likely function in separate pathways
      to regulate aspects of membrane merger and repair during cell fusion. 

PMID- 25595449
TI  - 17alpha-Estradiol: a candidate neuroserm and non-feminizing estrogen for
      postmenopausal neuronal complications.
AB  - Extensive evidence suggests that decline in ovarian function with menopause is
      associated with neuronal dysfunction. Major cause of this is rise in oxidative
      stress and inflammatory cytokines because of estrogen deficiency. 17beta
      Estradiol (E2, hormone with potent antioxidant and anti-inflammatory activity)
      has profound protective actions on multiple organ systems, but feminizing side
      effects of beta-estradiol limits its clinical efficacy. 17alpha-Estradiol
      (E2alpha), a non feminizing congener, gives a ray of hope to the scientific
      community as an alternative strategy to treat menopause associated neuronal
      pathologies. We assessed the protective actions of 17alpha-estradiol (5,
      10MUg/kg) against cognitive deficits, depression and motor coordination after
      4weeks of ovariectomy in rats and compared its efficacy with E2 at same doses.
      After the behavioral assay animals were sacrificed and their brains were
      harvested for biochemical studies. Uterine weights were also assessed. E2 and
      E2alpha (5, 10MUg/kg) were equally protective against attenuating cognitive
      deficits, depressive symptoms and motor incoordination in OVX rats. Both
      demonstrated significant antioxidant activity and E2, but not E2alpha, increased
      serum estradiol levels and proliferated uterine weights, markers of feminizing
      action. It can thus be concluded that E2alpha offers safe alternative to E2 in
      protecting against menopausal neuropathologies. 

PMID- 25595448
TI  - Neuronal nucleus and cytoplasm volume deficit in children with autism and volume
      increase in adolescents and adults.
AB  - INTRODUCTION: Characterization of the type and topography of structural changes
      and their alterations throughout the lifespan of individuals with autism is
      essential for understanding the mechanisms contributing to the autistic
      phenotype. The aim of this stereological study of neurons in 16 brain structures
      of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish
      the course of neuronal nuclear and cytoplasmic volume changes throughout the
      lifespan of individuals with autism. RESULTS: Our data indicate that a deficit of
      neuronal soma volume in children with autism is associated with deficits in the
      volume of the neuronal nucleus and cytoplasm. The significant deficits of
      neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical
      structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic
      children suggest a global nature of brain developmental abnormalities, but with
      region-specific differences in the severity of neuronal pathology. The observed
      increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young
      adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched
      control subjects reveal opposite trajectories throughout the lifespan. The
      deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined
      regions in children with autism, and in neuronal cytoplasmic volumes from 1% to
      31%, as well as the broader range of interindividual differences for the nuclear
      than the cytoplasmic volume deficits, suggest a partial distinction between
      nuclear and cytoplasmic pathology. CONCLUSIONS: The most severe deficit of both
      neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children
      appears to be a reflection of early developmental alterations that may have a
      major contribution to the autistic phenotype. The broad range of functions of the
      affected structures implies that their developmental and age-associated
      abnormalities contribute not only to the diagnostic features of autism but also
      to the broad spectrum of clinical alterations associated with autism. Lack of
      clinical improvement in autistic teenagers and adults indicates that the observed
      increase in neuron nucleus and cytoplasm volume close to control level does not
      normalize brain function.

PMID- 25595450
TI  - An expeditious synthesis of spinasterol and schottenol, two phytosterols present
      in argan oil and in cactus pear seed oil, and evaluation of their biological
      activities on cells of the central nervous system.
AB  - Spinasterol and schottenol, two phytosterols present in argan oil and in cactus
      pear seed oil, were synthesized from commercially available stigmasterol by a
      four steps reactions. In addition, the effects of these phytosterols on cell
      growth and mitochondrial activity were evaluated on 158N murine oligodendrocytes,
      C6 rat glioma cells, and SK-N-BE human neuronal cells with the crystal violet
      test and the MTT test, respectively. The effects of spinasterol and schottenol
      were compared with 7-ketocholesterol (7KC) and ferulic acid, which is also
      present in argan and cactus pear seed oil. Whatever the cells considered, dose
      dependent cytotoxic effects of 7KC were observed whereas no or slight effects of
      ferulic acid were found. With spinasterol and schottenol, no or slight effects on
      cell growth were detected. With spinasterol, reduced mitochondrial activities (30
      50%) were found on 158N and C6 cells; no effect was found on SK-N-BE. With
      schottenol, reduced mitochondrial activity were revealed on 158N (50%) and C6 (10
      20%) cells; no effect was found on SK-N-BE. Altogether, these data suggest that
      spinasterol and schottenol can modulate mitochondrial activity and might
      therefore influence cell metabolism. 

PMID- 25595451
TI  - Effect of estetrol on Beta-Endorphin level in female rats.
AB  - INTRODUCTION: Estetrol (E4), a naturally occurring estrogen produced exclusively
      by human fetal liver, is currently being evaluated for potential use in
      contraception and menopausal care in humans. The present study was designed to
      profile E4 effects on the central nervous system, to assess the in vivo effects
      of E4 administration on Beta-Endorphin (beta-END) release in specific brain
      structures and to evaluate whether E4 has synergic or antagonistic effects on
      estradiol-mediated beta-END synthesis. EXPERIMENTAL: Intact female adult rats
      received different doses of E4 and ovariectomized (OVX) rats received different
      doses of E4 or E2V or combinations of both drugs. The concentrations of beta-END
      were assessed in the frontal and parietal cortex, hippocampus, hypothalamus,
      neurointermediate lobe, anterior pituitary and plasma. RESULTS: E4 at the dose of
      1mg/kg/day did not alter beta-END content in most brain areas, as well as, plasma
      levels of intact animals E4 administered at a dose of 5mg/kg/day decreased beta
      END content in the hippocampus, hypothalamus, and in the neurointermediate lobe,
      as well as, plasma levels, compared to intact animals receiving vehicle. E4
      increased beta-END values in the frontal cortex, but not in the plasma, following
      the administration of 1mg/kg/day in OVX rats, whereas treatment with 5mg/kg/day
      in OVX rats induced a significant increase in beta-END levels in most brain areas
      and in the plasma. However, in the presence of estradiol, E4 showed an estrogen
      antagonistic effect in selected brain structures at the dose of 5mg/kg/day and in
      plasma levels of beta-END at the dose of 1mg/kg/day and 5mg/kg/day. CONCLUSION:
      In OVX rats, E4 increases CNS and peripheral levels of beta-END, behaving as a
      weak estrogen-agonist. The antagonistic effect observed after combined estradiol
      and E4 administration further profiles E4 as a natural SERM.

PMID- 25595452
TI  - Skeletal stability after bilateral sagittal split osteotomy or distraction
      osteogenesis of the mandible: a randomized clinical trial.
AB  - A randomized clinical trial was carried out to evaluate postoperative stability
      after mandibular advancements in non-syndromal class II patients with a bilateral
      sagittal split osteotomy (BSSO) or distraction osteogenesis (DO). In total 32
      patients could be included in the BSSO group and 34 patients in the DO group. The
      BSSO was converted to a unilateral procedure for one patient, and two patients in
      the BSSO group were lost during follow-up. A total 63 patients could be
      evaluated, 29 in the BSSO group and 34 in the DO group. Advancement was
      comparable in the two groups (mean 7.2mm). The mean follow-up period was 23.8
      months (range 11-50 months). Lateral cephalograms were hand-traced. Horizontal
      relapse was measured in Y-B (mm) and SNB ( degrees ). For DO this was -0.324 mm
      and -0.250 degrees , and for BSSO this was -0.448 mm and -0.259 degrees ,
      respectively (both not significant; NS). Vertical relapse measured in X-B was 
      0.074 mm for DO and -0.034 mm for BSSO (NS). The magnitude of advancement, a high
      mandibular plane angle, age and gender were not identified as independent risk
      factors for relapse. In conclusion, a BSSO and DO gave both similar stable
      results in advancements of the mandible up to 10mm.

PMID- 25595453
TI  - Respiratory complexes III and IV can each bind two molecules of cytochrome c at
      low ionic strength.
AB  - The transient interactions of respiratory cytochrome c with complexes III and IV
      is herein investigated by using heterologous proteins, namely human cytochrome c,
      the soluble domain of plant cytochrome c1 and bovine cytochrome c oxidase. The
      binding molecular mechanisms of the resulting cross-complexes have been analyzed
      by Nuclear Magnetic Resonance and Isothermal Titration Calorimetry. Our data
      reveal that the two cytochrome c-involving adducts possess a 2:1 stoichiometry -
      that is, two cytochrome c molecules per adduct - at low ionic strength. We
      conclude that such extra binding sites at the surfaces of complexes III and IV
      can facilitate the turnover and sliding of cytochrome c molecules and, therefore,
      the electron transfer within respiratory supercomplexes. 

PMID- 25595454
TI  - Structural insights into the catalytic reaction that is involved in the
      reorientation of Trp238 at the substrate-binding site in GH13 dextran
      glucosidase.
AB  - Streptococcus mutans dextran glucosidase (SmDG) belongs to glycoside hydrolase
      family 13, and catalyzes both the hydrolysis of substrates such as
      isomaltooligosaccharides and subsequent transglucosylation to form alpha-(1->6)
      glucosidic linkage at the substrate non-reducing ends. Here, we report the 2.4A
      resolution crystal structure of glucosyl-enzyme intermediate of SmDG. In the
      obtained structure, the Trp238 side-chain that constitutes the substrate-binding
      site turned away from the active pocket, concurrently with conformational changes
      of the nucleophile and the acid/base residues. Different conformations of Trp238
      in each reaction stage indicated its flexibility. Considering the results of
      kinetic analyses, such flexibility may reflect a requirement for the reaction
      mechanism of SmDG.

PMID- 25595455
TI  - FAM19A3, a novel secreted protein, modulates the microglia/macrophage
      polarization dynamics and ameliorates cerebral ischemia.
AB  - In this study, we have identified FAM19A3 as a gene that is significantly
      upregulated in the microglia in the middle cerebral artery occlusion (MCAO) mouse
      model. FAM19A3 expression and secretion were promoted by M2 stimuli, and this
      indicated that FAM19A3 might be an M2-type gene. Indeed, recombinant FAM19A3
      promoted M2 polarization and inhibited M1 polarization of microglia in vitro.
      Similarly, recombinant FAM19A3 promoted M2 polarization of microglia and
      macrophages in vivo, and attenuated cerebral ischemia in the MCAO mouse model.
      Thus, the newly-identified secreted protein FAM19A3 modulates the
      microglia/macrophage polarization dynamics and ameliorates cerebral ischemia. 

PMID- 25595456
TI  - C-peptide evolution: generation from few structural restrictions of bioactivities
      not necessarily functional.
AB  - The proinsulin C-peptide has molecular, cellular and organismal activities but
      lacks disease-associated mutations or short-term loss-of-function effects. This
      dilemma between activity and function may be explained from its evolutionary
      setting with insulin as an ancestral partner. The charge, approximate length and
      flexibility of C-peptide are all that is required for the insulin interactions,
      while remaining aspects are free to evolve, where new bioactivities can emerge.
      They can initially be transient, weak, and non-functional, but may gradually be
      consolidated. In this manner, C-peptide may have acquired multiple bioactivities,
      explaining why some yet have limited functions but could represent early-stage
      hormonal-like activities. 

PMID- 25595457
TI  - The coronary artery disease-associated gene C6ORF105 is expressed in human
      macrophages under the transcriptional control of PPARgamma.
AB  - Coronary artery disease (CAD) is a major cause of morbidity and mortality.
      Mutations in C6ORF105, associated with decreased gene expression, positively
      correlate with the risk of CAD in Chinese populations. Moreover, the C6ORF105
      encoded protein may play a role in coagulation. Here, we report that C6ORF105
      gene expression is lower in circulating mononuclear cells from obese diabetic
      than lean subjects. Moreover, C6ORF105 is expressed in human macrophages and
      atherosclerotic lesions, where its expression positively correlates with
      expression of the transcription factor Peroxisome Proliferator-Activated Receptor
      (PPAR)gamma. Activation of PPARgamma increases, in a PPARgamma-dependent manner,
      the expression of C6ORF105 in human macrophages and atherosclerotic lesions. 

PMID- 25595460
TI  - Review of 2014: Jack Perkins Prize, Journal Impact Factor, and Editorial Board of
      Medical Engineering & Physics.

PMID- 25595459
TI  - Association of low GLP-1 with oxidative stress is related to cardiac disease and
      outcome in patients with type 2 diabetes mellitus: a pilot study.
AB  - Oxidative stress (OS) contributes to cardiovascular damage in type 2 diabetes
      mellitus (T2DM). The peptide glucagon-like peptide-1 (GLP-1) inhibits OS and
      exerts cardiovascular protective actions. Our aim was to investigate whether
      cardiac remodeling (CR) and cardiovascular events (CVE) are associated with
      circulating GLP-1 and biomarkers of OS in T2DM patients. We also studied GLP-1
      antioxidant effects in a model of cardiomyocyte lipotoxicity. We examined 72 T2DM
      patients with no coronary or valve heart disease and 14 nondiabetic subjects. A
      median of 6 years follow-up information was obtained in 60 patients. Circulating
      GLP-1, dipeptidyl peptidase-4 activity, and biomarkers of OS were quantified. In
      T2DM patients, circulating GLP-1 decreased and OS biomarkers increased, compared
      with nondiabetics. Plasma GLP-1 was inversely correlated with serum 3
      nitrotyrosine in T2DM patients. Patients showing high circulating 3-nitrotyrosine
      and low GLP-1 levels exhibited CR and higher risk for CVE, compared to the
      remaining patients. In palmitate-stimulated HL-1 cardiomyocytes, GLP-1 reduced
      cytosolic and mitochondrial oxidative stress, increased mitochondrial ATP
      synthase expression, partially restored mitochondrial membrane permeability and
      cytochrome c oxidase activity, blunted leakage of creatine to the extracellular
      medium, and inhibited oxidative damage in total and mitochondrial DNA. These
      results suggest that T2DM patients with reduced circulating GLP-1 and exacerbated
      OS may exhibit CR and be at higher risk for CVE. In addition, GLP-1 exerts
      antioxidant effects in HL-1 palmitate-overloaded cardiomyocytes. It is proposed
      that therapies aimed to increase GLP-1 may counteract OS, protect from CR, and
      prevent CVE in patients with T2DM. 

PMID- 25595461
TI  - Variability in developmental timings of the knee in young American children as
      assessed through Pyle and Hoerr's radiographic atlas.
AB  - This study examines the accuracy of the Pyle and Hoerr radiographic atlas
      technique in an effort to document the extent of normal variation associated with
      developmental timings in the knee for purposes of age estimation. The atlas has
      been previously tested; however, accuracy rates were produced from a dataset,
      which spread in age from mostly 7-16 years. This study took a closer look at the
      younger age groups, examining radiographs from 297 children (147 female and 150
      male) from birth to 6 years. Standard deviations representing the difference
      between the skeletal and chronological age were calculated according to two
      groupings. Each group represents episodes, or time periods, of differential
      developmental rates as expressed through the number of plates within the atlas
      dedicated to documenting each year of life. The beginning year of life is
      characterized by the most rapid of development as represented by the numerous
      image plates used to depict this time period. Individuals assigned to plates with
      a skeletal age between birth and 1 year were grouped collectively to document the
      variation associated with such rapidly changing morphology (SD = 2.5 months in
      female children; 2.3 months in male children). Years 1-3.8 years (female) and 1
      4.5 years (male) were represented by two or three images within the atlas, and
      therefore, individuals assigned to plates with a skeletal age falling within this
      range were placed within a second grouping (SD = 5.2 months in female children;
      7.0 months in male children). As expected, variation was observed to decrease as
      developmental processes accelerated in the younger children. The newly calculated
      standard deviations offer tighter predictions for estimating age in young
      children while at the same time maintaining an acceptable width that accounts for
      normal variation in developmental timings.

PMID- 25595463
TI  - Energy metabolism disorders in rare and common diseases. Toward bioenergetic
      modulation therapy and the training of a new generation of European scientists.
AB  - Energy metabolism alterations are found in a large number of rare and common
      diseases of genetic or environmental origin. The number of patients that could
      benefit from bioenergetic modulation therapy (BIOMET) is therefore very important
      and includes individuals with pathologies as diverse as mitochondrial diseases,
      acute coronary syndrome, chronic kidney disease, asthma or even cancer. Although,
      the alteration of energy metabolism is disease specific and sometimes patient
      specific, the strategies for BIOMET could be common and target a series of
      bioenergetic regulatory mechanisms discussed in this article. An excellent
      training of scientists in the field of energy metabolism, related human diseases
      and drug discovery is also crucial to form a young generation of MDs, PHDs and
      Pharma or CRO-group leaders who will discover novel personalized bioenergetic
      medicines, through pharmacology, genetics, nutrition or adapted exercise
      training. The Mitochondrial European Educational Training (MEET) consortium was
      created to pursue this goal, and we dedicated here a special issue of Organelle
      in Focus (OiF) to highlight their objectives. A total of 10 OiFs articles
      constitute this Directed Issue on Mitochondrial Medicine. As part of this
      editorial article, we asked timely questions to the PR. Jan W. Smeitink,
      professor of Mitochondrial Medicine and CEO of Khondrion, a mitochondrial
      medicine company. He shared with us his objectives and strategies for the study
      of mitochondrial diseases and the identification of future treatments. This
      article is part of a Directed Issue entitled: Energy Metabolism Disorders and
      Therapies. 

PMID- 25595462
TI  - Shoulder limited joint mobility in people with diabetes mellitus.
AB  - BACKGROUND: Limited joint mobility at the shoulder is an understudied problem in
      people with diabetes mellitus. The purpose of this study was to determine the
      differences in shoulder kinematics between a group with diabetes and those
      without diabetes. METHODS: Fifty-two participants were recruited, 26 with
      diabetes and 26 non-diabetes controls (matched for age, BMI and sex). Three
      dimensional position of the trunk, scapula and humerus were collected using
      electromagnetic tracking sensors during scapular plane elevation and rotation
      movements. FINDINGS: Glenohumeral external rotation was reduced by 11.1 degrees 
      16.3 degrees  (P<0.05) throughout the humerothoracic elevation range of motion,
      from neutral to peak elevation, in individuals with diabetes as compared to
      controls. Peak humerothoracic elevation was decreased by 10-14 degrees , and peak
      external rotation with the arm abducted was decreased 22 degrees  in the diabetes
      group compared to controls (P<0.05). Scapulothoracic and glenohumeral internal
      rotation motions were not different between the two groups. INTERPRETATION:
      Shoulder limited joint mobility, in particular decreased external rotation, was
      seen in individuals with diabetes as compared to control participants. Future
      research should investigate causes of diabetic limited joint mobility and
      strategies to improve shoulder mobility and prevent additional detrimental
      changes in movement and function.

PMID- 25595464
TI  - ST2 deletion increases inflammatory bone destruction in experimentally induced
      periapical lesions in mice.
AB  - INTRODUCTION: ST2 is a member of the interleukin (IL)-1 receptor family, and IL
      33 is its natural ligand. ST2 signaling promotes Th2 immune response in allergy,
      autoimmunity, and chronic inflammatory disorders, but its role in the
      pathogenesis of periapical lesions is unknown. The purpose of this study was to
      investigate whether ST2 gene deletion affects the development of experimentally
      induced periapical lesions in mice. METHODS: Pulps of mandibular molars from wild
      type (WT) and ST2 knockout (ST2(-)/(-)) BALB/c mice were exposed and left open to
      the oral environment. After death, hemi-mandibles were isolated and prepared for
      histologic, immunohistochemical, and flow cytometric analysis. RESULTS: The
      expression of IL-33 and its receptor ST2 was higher in periapical lesions in WT
      mice compared with normal root apices (both P < .05). The increased periapical
      bone loss observed in ST2(-)/(-) mice was associated with enhanced influx of
      neutrophils, CD3+ CXCR3+ Th1 cells, and CD3+ CCR6+ Th17 cells and increased
      number of tartrate-resistant acid phosphatase+ osteoclasts (all P < .05).
      Furthermore, periapical lesions in ST2(-)/(-) mice contained increased
      percentages of T cells expressing interferon-gamma, IL-17, tumor necrosis factor
      alpha, and IL-6 (all P < .05). In comparison with WT mice, CD3+ receptor
      activator of nuclear factor kappa B ligand+ T cells were increased, whereas CD3+
      osteoprotegerin+ T cells were decreased in the lesions of ST2(-)/(-) mice (both P
      < .05). CONCLUSIONS: ST2 deletion increases inflammatory bone loss in
      experimental periapical lesions in mice, which is associated with enhanced
      Th1/Th17 cell mediated periapical immune responses and increased
      osteoclastogenesis.

PMID- 25595465
TI  - Evaluation of the maintenance of the apical limit during instrumentation with
      hybrid equipment in rotary and reciprocating modes.
AB  - INTRODUCTION: The objective of the present study was to evaluate ex vivo the
      maintenance of the apical limit during instrumentation with the Root ZX (J
      Morita, Tokyo, Japan) and VDW Gold (VDW GbmH, Munich, Germany) hybrid devices in
      rotary and reciprocating modes and determine the possible function variations of
      different preparation levels (0.0 mm and -1.0 mm). METHODS: Seventy-two human
      uniradicular mandibular premolars, which had their coronal access performed and
      their apical foramen (AF) standardized (200 MUm) were used. After their
      randomized division, the root canals were chemically mechanically prepared with
      #F4 ProTaper (Dentsply Maillefer, Ballaigues, Switzerland) and #R40 Reciproc (VDW
      GbmH) instruments. At the end of the instrumentation, the last instrument was
      fixed, and 4.0 mm of the apical portion was worn, permitting the measurement of
      the distance between the instrument tips and the AF. RESULTS: The determined
      precision values of 0.0 and -1.0 mm were 100% and 33.4% (Root), 100% and 41.6%
      (VDW Gold with rotary movement) and 100% and 33.3% (VDW Gold with reciprocating
      movement), respectively, with a margin of +/-0.5 mm. No statistical differences
      were found with respect to the comparisons of every level of preparation.
      However, significant differences were found when comparing the groups with rotary
      function at the different levels, with a higher precision for the groups that
      reached the AF. CONCLUSIONS: It was concluded that both devices, independent of
      the function used, were more efficient in the maintenance of the apical limit
      when used until the AF; however, such reliability was compromised when -1.0 mm
      from the apical limit was established.

PMID- 25595466
TI  - The effect of alteration of the exposure parameters of a cone-beam computed
      tomographic scan on the diagnosis of simulated horizontal root fractures.
AB  - INTRODUCTION: The purpose of this study was to determine the effect of alteration
      of the exposure parameters of a cone-beam computed tomographic (CBCT) scan on the
      detection of the presence or absence of simulated horizontal root fractures
      (HRFs). METHODS: CBCT scans of the lower incisor region of 5 human, dentate, dry
      mandibles were performed with 11 different exposure parameters. Ten teeth were
      extracted, and simulated HRFs were created near the apical thirds of the root.
      The fragments were reattached and the teeth replanted. The mandibles were
      rescanned over the same range of exposure parameters. Receiver operator
      characteristic analysis and kappa analyses were performed to assess diagnostic
      accuracy and intra- and interexaminer agreement for each scan setting. RESULTS:
      The overall Az value (area under receiver operator curve) for the manufacturer's
      default setting was 0.95. The sensitivity was 0.94 and the specificity 0.96. A
      reduction in the tube current to 2 mA at 360 degrees  or 180 degrees  of rotation
      had no significant impact on the Az value, sensitivity, or specificity of CBCT
      imaging in the detection simulated HRFs. A reduction in the current to 1 mA at
      360 degrees  or 180 degrees  of rotation significantly reduced the Az value (0.9
      and 0.75, respectively) in comparison with the manufacturer's default setting (P
      < .05). CONCLUSIONS: CBCT scans are an accurate and reliable technique to detect
      HRFs. Within the limitations of this study, it is possible to reduce the
      radiation dose by altering the exposure parameters without a significant
      reduction in the diagnostic quality of the CBCT scan generated for the detection
      of HRFs.

PMID- 25595467
TI  - A retrospective comparative study of cone-beam computed tomography versus
      rendered panoramic images in identifying the presence, types, and characteristics
      of dens invaginatus in a Turkish population.
AB  - INTRODUCTION: This study assessed the presence, characteristics, and type of dens
      invaginatus (DI) by using cone-beam computed tomography (CBCT) and panoramic
      images rendered from CBCT images. In addition, the findings of the imaging
      techniques were compared. METHODS: We evaluated 300 CBCT images to determine the
      type of DI, the presence of an impacted tooth near the DI, and the presence of
      apical pathosis. The McNemar test was used to compare the prevalence of DI
      according to CBCT and panoramic images rendered from CBCT images. RESULTS: The
      presence of DI was lower on panoramic images rendered from CBCT images (3% of the
      patients) compared with on CBCT images (10.7% of the patients) (P < .001).
      According to the CBCT images, the distribution of teeth with DI was as follows:
      maxillary lateral incisors (75%), maxillary central incisors (6.8%), mandibular
      premolars (4.6%), mesiodens (9%), maxillary canines (2.3%), and mandibular
      canines (2.3%). Type I DI was the most commonly observed type of invaginatus
      (65.9%), followed by type II (29.5%) and type III (4.6%). All patients with type
      III DI and 25% of the patients with type II DI had apical pathosis at the time of
      referral, but periapical lesions were not observed in teeth with type I DI. In
      total, 13.6% of DI cases had impacted teeth. CONCLUSIONS: CBCT can be recommended
      as an effective diagnostic device for identifying DI because it provides an
      accurate representation of the external and internal dental anatomy.

PMID- 25595468
TI  - Influence of root canal disinfectants on growth factor release from dentin.
AB  - INTRODUCTION: During dentinogenesis, growth factors become entrapped in the
      dentin matrix that can later be released by demineralization. Their effect on
      pulpal stem cell migration, proliferation, and differentiation could be
      beneficial for regenerative endodontic therapies. However, precondition for
      success, as for conventional root canal treatment, will be sufficient
      disinfection of the root canal system. Various irrigation solutions and
      intracanal dressings are available for clinical use. The aim of this study was 2
      fold: to identify a demineralizing solution suitable for growth factor release
      directly from dentin and to evaluate whether commonly used disinfectants for
      endodontic treatment will compromise this effect. METHODS: Dentin disks were
      prepared from extracted human teeth and treated with EDTA or citric acid at
      different concentrations or pH for different exposure periods. The amount of
      transforming growth factor-beta1 (TGF-beta1), fibroblast growth factor 2, and
      vascular endothelial growth factor were quantified via enzyme-linked
      immunosorbent assay and visualized by gold labeling. Subsequently, different
      irrigation solutions (5.25% sodium hypochloride, 0.12% chlorhexidine digluconate)
      and intracanal dressings (corticoid-antibiotic paste, calcium hydroxide: water
      based and oil-based, triple antibiotic paste, chlorhexidine gel) were tested, and
      the release of TGF-beta1 was measured after a subsequent conditioning step with
      EDTA. RESULTS: Conditioning with 10% EDTA at pH 7 rendered the highest amounts of
      TGF-beta1 among all test solutions. Fibroblast growth factor 2 and vascular
      endothelial growth factor were detected after EDTA conditioning at minute
      concentrations. Irrigation with chlorhexidine before EDTA conditioning increased
      TGF-beta1 release; sodium hypochloride had the opposite effect. All tested
      intracanal dressings interfered with TGF-beta1 release except water-based calcium
      hydroxide. CONCLUSIONS: Growth factors can be released directly from dentin via
      EDTA conditioning. The use of disinfecting solutions or medicaments can amplify
      or attenuate this effect.

PMID- 25595469
TI  - A clinical study of COPD severity assessment by primary care physicians and their
      patients compared with spirometry.
AB  - PURPOSE: Primary care physicians often do not use spirometry to confirm the
      diagnosis of chronic obstructive pulmonary disease. This project was designed to
      see how well physicians' impressions about their patients' chronic obstructive
      pulmonary disease severity correlate with the severity of airflow obstruction
      measured by spirometry and to assess whether spirometry results subsequently
      changed the physicians' opinions about chronic obstructive pulmonary disease
      severity and treatment. METHODS: We performed a multicenter, cross-sectional,
      observational study conducted in 83 primary care clinics from across the United
      States. A total of 899 patients with a clinical diagnosis of chronic obstructive
      pulmonary disease completed a questionnaire and spirometry testing. Physicians
      completed a questionnaire and case report forms. Concordance among physician
      ratings, patient ratings, and spirometry results was evaluated. RESULTS:
      Physicians' chronic obstructive pulmonary disease severity ratings before
      spirometry were accurate for only 30% of patients with evaluable spirometry
      results, and disease severity in 41% of patients was underestimated. Physicians
      also underestimated severity compared with patients' self-assessment among 42% of
      those with evaluable results. After spirometry, physicians changed their opinions
      on the severity for 30% of patients and recommended treatment changes for 37%.
      Only 75% of patients performed at least 1 high-quality spirometry test; however,
      the physicians' opinions and treatment decisions were similar regardless of
      suboptimal test results. CONCLUSIONS: Without performing spirometry, physicians
      are likely to underestimate their patients' chronic obstructive pulmonary disease
      severity or inadequately characterize their patients' lung disease. Spirometry
      changed the physicians' clinical impressions and treatments for approximately one
      third of these patients; thus, spirometry is a valuable tool for chronic
      obstructive pulmonary disease management in primary care.

PMID- 25595472
TI  - Microstructure, mechanical properties, castability and in vitro biocompatibility
      of Ti-Bi alloys developed for dental applications.
AB  - In this study, the microstructure, mechanical properties, castability,
      electrochemical behaviors, cytotoxicity and hemocompatibility of Ti-Bi alloys
      with pure Ti as control were systematically investigated to assess their
      potential applications in the dental field. The experimental results showed that,
      except for the Ti-20Bi alloy, the microstructure of all other Ti-Bi alloys
      exhibit single alpha-Ti phase, while Ti-20Bi alloy is consisted of mainly alpha
      Ti phase and a small amount of BiTi2 and BiTi3 phases. The tensile strength,
      hardness and wear resistance of Ti-Bi alloys were demonstrated to be improved
      monotonically with the increase of Bi content. The castability test showed that
      Ti-2Bi alloy increased the castability of pure Ti by 11.7%. The studied Ti-Bi
      alloys showed better corrosion resistance than pure Ti in both AS (artificial
      saliva) and ASFL (AS containing 0.2% NaF and 0.3% lactic acid) solutions. The
      concentrations of both Ti ion and Bi ion released from Ti-Bi alloys are extremely
      low in AS, ASF (AS containing 0.2% NaF) and ASL (AS containing 0.3% lactic acid)
      solutions. However, in ASFL solution, a large number of Ti and Bi ions are
      released. In addition, Ti-Bi alloys produced no significant deleterious effect to
      L929 cells and MG63 cells, similar to pure Ti, indicating a good in vitro
      biocompatibility. Besides, both L929 and MG63 cells perform excellent cell
      adhesion ability on Ti-Bi alloys. The hemolysis test exhibited that Ti-Bi alloys
      have an ultra-low hemolysis percentage below 1% and are considered nonhemolytic.
      To sum up, the Ti-2Bi alloy exhibits the optimal comprehensive performance and
      has great potential for dental applications. 

PMID- 25595470
TI  - Substantial Discrepancy Between Fluid and Weight Loss During Acute Decompensated
      Heart Failure Treatment.
AB  - BACKGROUND: Net fluid and weight loss are used ubiquitously to monitor diuretic
      response in acute decompensated heart failure research and patient care. However,
      the performance of these metrics has never been evaluated critically. The weight
      and volume of aqueous fluids such as urine should be correlated nearly perfectly
      and with very good agreement. As a result, significant discrepancy between fluid
      and weight loss during the treatment of acute decompensated heart failure would
      indicate measurement error in 1 or both of the parameters. METHODS: The
      correlation and agreement (Bland-Altman method) between diuretic-induced fluid
      and weight loss were examined in 3 acute decompensated heart failure trials and
      cohorts: (1) Diuretic Optimization Strategies Evaluation (DOSE) (n = 254); (2)
      Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization
      Effectiveness (ESCAPE) (n = 348); and (3) Penn (n = 486). RESULTS: The
      correlation between fluid and weight loss was modest (DOSE r = 0.55; ESCAPE r =
      0.48; Penn r = 0.51; P < .001 for all), and the 95% limits of agreement were wide
      (DOSE -7.9 to 6.4 kg-L; ESCAPE -11.6 to 7.5 kg-L; Penn -14.5 to 11.3 kg-L). The
      median relative disagreement ranged from +/-47.0% to 63.5%. A bias toward greater
      fluid than weight loss was found across populations (-0.74 to -2.1 kg-L, P <=
      .002). A consistent pattern of baseline characteristics or in-hospital treatment
      parameters that could identify patients at risk of discordant fluid and weight
      loss was not found. CONCLUSIONS: Considerable discrepancy between fluid balance
      and weight loss is common in patients treated for acute decompensated heart
      failure. Awareness of the limitations inherent to these commonly used metrics and
      efforts to develop more reliable measures of diuresis are critical for both
      patient care and research in acute decompensated heart failure.

PMID- 25595471
TI  - Bimolecular based heparin and self-assembling hydrogel for tissue engineering
      applications.
AB  - One major goal of tissue engineering is to develop new biomaterials that are
      similar structurally and functionally to the extracellular matrix (ECM) to mimic
      natural cell environments. Recently, different types of biomaterials have been
      developed for tissue engineering applications. Among them, self-assembling
      peptides are attractive candidates to create artificial cellular niches, because
      their nanoscale network and biomechanical properties are similar to those of the
      natural ECM. Here, we describe the development of a new biomaterial for tissue
      engineering composed by a simple combination of the self-assembling peptide RAD16
      I and heparin sodium salt. As a consequence of the presence of heparin moieties
      the material acquired enhances the capacity of specific binding and release of
      growth factors (GFs) with heparin binding affinity such as VEGF165. Promising
      results were obtained in the vascular tissue engineering area, where the new
      composite material supported the development of tubular-like structures within a
      three dimensional (3D) culture model. Moreover, the new scaffold enhances the
      cell survival and chondrogenic commitment of adipose-derived stem cells (ADSC).
      Interestingly, the expression of specific markers of mature cartilage tissue
      including collagen type II was confirmed by western blot and real-time PCR.
      Furthermore, positive staining for proteoglycans (PGs) indicated the synthesis of
      cartilage tissue ECM components. Finally, the constructs did not mineralize and
      exhibited mechanical properties of a tissue undergoing chondrogenesis.
      Altogether, these results suggest that the new composite is a promising "easy to
      prepare" material for different reparative and regenerative applications. 

PMID- 25595473
TI  - Folate-bovine serum albumin functionalized polymeric micelles loaded with
      superparamagnetic iron oxide nanoparticles for tumor targeting and magnetic
      resonance imaging.
AB  - Polymeric micelles functionalized with folate conjugated bovine serum albumin (FA
      BSA) and loaded with superparamagnetic iron oxide nanoparticles (SPIONs) are
      investigated as a specific contrast agent for tumor targeting and magnetic
      resonance imaging (MRI) in vitro and in vivo. The SPIONs-loaded polymeric
      micelles are produced by self-assembly of amphiphilic poly(HFMA-co-MOTAC)-g-PEGMA
      copolymers and oleic acid modified Fe3O4 nanoparticles and functionalized with FA
      BSA by electrostatic interaction. The FA-BSA modified magnetic micelles have a
      hydrodynamic diameter of 196.1 nm, saturation magnetization of 5.5 emu/g, and
      transverse relaxivity of 167.0 mM(-1) S(-1). In vitro MR imaging, Prussian blue
      staining, and intracellular iron determination studies demonstrate that the
      folate-functionalized magnetic micelles have larger cellular uptake against the
      folate-receptor positive hepatoma cells Bel-7402 than the unmodified magnetic
      micelles. In vivo MR imaging conducted on nude mice bearing the Bel-7402
      xenografts after bolus intravenous administration reveals excellent tumor
      targeting and MR imaging capabilities, especially at 24h post-injection. These
      findings suggest the potential of FA-BSA modified magnetic micelles as targeting
      MRI probe in tumor detection.

PMID- 25595474
TI  - Triazine-modified dendrimer for efficient TRAIL gene therapy in osteosarcoma.
AB  - Osteosarcoma is a high-grade malignant bone tumor that usually develops in the
      teenagers. Despite improvement in therapy, the five-year survival rate is poor
      for patients not responding to treatment or with metastases. Tumor necrosis
      factor (TNF) related apoptosis inducing ligand (TRAIL) gene therapy is a new
      strategy in the treatment of cancers, however, the lack of efficient and low
      toxic vectors remains the major obstacle in TRAIL gene therapy. In this study, a
      triazine-modified dendrimer G5-DAT66 was synthesized and used as a vector for
      TRAIL gene therapy in vitro and in vivo. The material shows much higher
      transfection efficacy on osteosarcoma MG-63 cell line than commercial
      transfection reagents such as Lipofectamine 2000 and SuperFect. It effectively
      induces apoptosis in MG-63 cells and three-dimensional MG-63 cell cultures when
      delivering a TRAIL plasmid. In vivo studies further prove that G5-DAT66
      efficiently transfects TRAIL plasmid in tumors and inhibits tumor growth in
      osteosarcoma-bearing mice. These results suggest that triazine-modified dendrimer
      has promising potential for TRAIL gene therapy in osteosarcoma. 

PMID- 25595475
TI  - nDEP-driven cell patterning and bottom-up construction of cell aggregates using a
      new bioelectronic chip.
AB  - Creating cell aggregates of controlled size and shape and patterning cells on
      substrates using a bottom-up approach constitutes important challenges for tissue
      engineering applications and studies of cell-cell interactions. In this paper, we
      report nDEP (negative dielectrophoresis) driven assembly of cells as compact
      aggregates or onto defined areas using a new bioelectronic chip. This chip is
      composed of a quadripolar electrode array obtained using coplanar electrodes
      partially covered with a thin, micropatterned PDMS membrane. This thin PDMS layer
      was coated with poly-L-lysine and played the role of adhesive substrate for cell
      patterning. For the formation of detachable cell aggregates, the PDMS was not
      pretreated and cells were simply immobilized into assemblies maintained by cell
      cell adhesion after the electric field removal. Cell viability after exposition
      to DEP buffer was also assessed, as well as cell spreading activity following DEP
      driven assembly.

PMID- 25595476
TI  - Extracorporeal membrane oxygenation-hemostatic complications.
AB  - The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and
      respiratory failure has increased in recent years. Improvements in ECMO
      oxygenator and pump technologies have aided this increase in utilization.
      Additionally, reports of successful outcomes in supporting patients with
      respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during
      cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients
      requiring ECMO are a heterogenous group of critically ill patients with cardiac
      and respiratory failure. Bleeding and thrombotic complications remain a leading
      cause of morbidity and mortality in patients on ECMO. In this review, we describe
      the mechanisms and management of hemostatic, thrombotic and hemolytic
      complications during ECMO support. 

PMID- 25595477
TI  - Spironucleus meleagridis, an enteric diplomonad protozoan of cockatiels
      (Nymphicus hollandicus): preliminary molecular characterization and association
      with clinical disease.
AB  - A flagellated enteric diplomonad protozoan consistent with Spironucleus
      meleagridis (formerly Hexamita meleagridis) associated with gastrointestinal
      disease and mortality in psittacine birds including cockatiels (Nymphicus
      hollandicus) has been sporadically described in the literature. However,
      molecular characterization of psittacine protozoal isolates had not yet been
      performed. The 16S rRNA gene from a protozoan persistently shed in the feces in a
      small group of cockatiels demonstrated a 98% molecular identity with S.
      meleagridis isolated from turkeys. Based on these sequence data, a diagnostic PCR
      assay was developed to detect the presence of S. meleagridis. Nineteen privately
      owned pet cockatiels from unrelated households were clinically evaluated. All
      birds microscopically positive for this organism were PCR positive, with several
      additional birds microscopically negative but PCR positive. Many of the birds
      identified as positive for S. meleagridis by fecal PCR had signs of
      gastrointestinal disease such as diarrhea, soft feces, and melena, whereas none
      of the birds that tested negative had gastrointestinal signs. Examination of
      feces from two unrelated cockatiel breeding facilities revealed 70% and 86% PCR
      positive rates. Prevalence of infection and incidence of clinical disease,
      including factors that lead to clinical manifestation such as viral, bacterial,
      or mycotic coinfections, are not yet known and warrant further study, but
      spironucleosis is likely an under-recognized disease in cockatiels. 

PMID- 25595479
TI  - Sexing in guinea fowls (Numida meleagris).
AB  - Despite the potentials and contributions of guinea fowls to economic and social
      life in Ghana, accurate sex identification in these birds is still a major
      problem. Three hundred and sixty guinea fowls (180 birds per sex) were used in
      determining a more accurate and farmer friendly sexing technique. The sexing
      methods explored were vent, biometric, and molecular techniques. Vent sexing was
      accomplished by measuring phalli in 28 and 32-week-old birds, while biometric
      sexing involved the measurement of morphometric traits and data analyzed using
      discriminant function analysis. Molecular sexing was carried out by DNA
      extraction and subsequent PCR using the 2550F/2718R primer set. Females had a
      wider (P<0.05) pelvic inlet than male birds from first week of age until the end
      of the study, while the opposite was true for wattle length. However, wattle
      length differed (P<0.05) between both sexes after 4 weeks of age. Combining the
      biometric variables in a discriminant function, males could be distinguished from
      females with an accuracy of 94%. During molecular sexing, the P2/P8 primer set
      was not effective in sexing guinea fowls because it amplified a single band in
      both sexes and in the same manner. The sex of guinea fowls was properly
      determined using the primer set 2550F/2718R. Females produced 2 bands of 396 bp
      and 344 bp, while males only produced the larger band. Phallus size in the 2
      sexes were distinguishable from 8 weeks of age, with males having longer and
      thicker (P<0.05) phalli than their female counterparts. Combining the 2 variables
      in a discriminate function, males and females could be distinguished with 98.3%
      accuracy. While the molecular method remains the most accurate sexing technique,
      the biometric method emerged as the most farmer friendly approach to sexing
      guinea fowls.

PMID- 25595478
TI  - Effects of feeding diets varying in energy and nutrient density to Hy-Line W-36
      laying hens on production performance and economics.
AB  - The objectives of this study were to evaluate the effects of feeding 5 different
      energy and nutrient dense diets to Hy-Line W-36 hens on long-term performance and
      economics. A total of 480 19 wk old Hy-Line W-36 Single Comb White Leghorn hens
      were weighed and randomly allocated to 6 replicate groups of 16 hens each (2
      adjacent cages containing 8 hens per cage, 60.9*58.4 cm) per dietary treatment in
      a randomized complete block design. The hens were fed 5 treatment diets
      formulated to contain 85, 90, 95, 100, and 105% of the energy and nutrient
      recommendations stated in the 2009 Hy-Line Variety W-36 Commercial Management
      Guide. Production performance was measured for 52 wk from 19 to 70 wk age. Over
      the course of the trial, a significant increasing linear response to increasing
      energy and nutrient density was seen for hen-day egg production, egg weight, egg
      mass, feed efficiency, energy intake, and body weight (BW). Feed intake showed no
      significant linear level response to increasing energy and nutrient density
      except during the early production cycle. No consistent responses were noted for
      egg quality, percent yolk, and percent egg solids throughout the study.
      Significant linear responses due to energy and nutrient density were seen for egg
      income, feed cost, and income minus feed cost. In general, as energy and nutrient
      density increased, egg income and feed cost per hen increased, but income minus
      feed cost decreased. Overall, these results indicate that feeding Hy-Line W-36
      hens increasing energy and nutrient-dense diets will increase egg production, egg
      weight, egg mass, feed efficiency, energy intake, BW, egg income, and feed cost,
      but decrease egg income minus feed cost. However, these benefits do not take
      effect in early production and seem to be most effective in later stages of the
      production cycle, perhaps "priming" the birds for better egg-production
      persistency with age.

PMID- 25595481
TI  - A temporal study of Salmonella enterica serotypes from broiler farms in Brazil.
AB  - The present study analyzes the characteristics of Salmonella spp. from broiler
      chicken farms in Brazil. In total, 82 Salmonella spp. strains were characterized
      by serotyping, determining susceptibility to antimicrobials, and using pulsed
      field gel electrophoresis (PFGE). Fifteen Salmonella serotypes were identified,
      among which Minnesota (40.24%), Infantis (14.63%), Heidelberg (7.31%),
      Senftenberg (6.09%), and Mbandaka (6.09%) were the most frequent. Salmonella
      Minnesota occurred mostly in the state of Mato Grosso do Sul and in one of the
      broiler companies surveyed. Approximately 60% of the strains were resistant to at
      least one of the antimicrobials tested. From these isolates, 17.07% were
      resistant to only one antimicrobial (tetracycline or streptomycin), and 9.75%
      were resistant to 3 or more antimicrobial classes. Thirteen resistance profiles
      were characterized, the most frequent of which were the resistance to
      tetracycline (15.85%); to the combination of trimethroprim with sulfamethoxazole,
      and tetracycline (10.97%); and to the combination of streptomycin and
      tetracycline (9.75%). Multiple correspondence analysis revealed that
      susceptibility or resistance of the analyzed strains and also particular
      Salmonella serotypes were associated with broiler-producing companies where the
      samples were collected. Strains presented high intraserotype genetic variability,
      as shown by the 64 PFGE profiles, suggesting the existence of several
      contamination sources in the surveyed farms. 

PMID- 25595480
TI  - Energy utilization and growth performance of chickens fed novel wheat inbred
      lines selected for different pentosan levels with and without xylanase
      supplementation.
AB  - Different F5 recombinant inbred lines from the cross Yumai 34*Ukrainka were grown
      in replicated trials on a single site in one harvest year at Rothamsted Research.
      A total of 10 samples from those lines were harvested and used in a broiler
      experiment. Twenty nutritionally complete meal-form diets that had 630 g/kg of
      wheat with different amounts of pentosan, with and without exogenous xylanase
      supplementation, were used to compare broiler growth performance and determine
      apparent metabolizable energy corrected for N retention (AMEn). We examined the
      relationship between the nutritive value of the wheat samples and their chemical
      compositions and results of quality tests. The amounts of total and water soluble
      pentosans in wheat samples ranged from 36.7 to 48.0 g/kg DM, and 6.7 to 11.6 g/kg
      DM, respectively. The mean crude oil and protein contents of the wheat samples
      were 10.5 and 143.9 g/kg DM, respectively. The average determined value for the
      kinematic viscosity was 0.0018 mPa.s, and 2.1 mPa.s for the dynamic viscosity.
      The AMEn of the wheat-based diets had a maximum range of 0.47 MJ/kg DM within the
      ten wheat samples that were tested. Xylanase supplementation improved (P<0.05)
      dietary AMEn, dry matter, and fat digestibility coefficients. There was a
      positive (P<0.05) relationship between in vitro kinematic viscosity of the wheat
      samples and the total pentosan content. There was a negative relationship between
      the total pentosan content in the wheat and broiler growth performance. An
      increase by 10 g of pentosan per kg of wheat reduced (P<0.001) daily feed intake
      and weight gain by 2.9 g and 3.5 g, respectively. The study shows that the
      feeding quality of wheat samples can be predicted by their total pentosan
      content. Supplementary xylanase improved energy and nutrient availability of all
      wheat samples that was independent of differences in pentosan content.

PMID- 25595482
TI  - The effects of extrusion of wheat distillers dried grains with solubles with or
      without an enzyme cocktail on performance of turkey hen poults.
AB  - Two experiments were conducted to determine if extrusion (EX) or enzymes (E)
      could overcome the restrictions (e.g., high fiber) of feeding wheat distillers
      dried grain with solubles (wDDGS) and improve its nutritional value for feeding
      turkeys. Two starter diets with either 0 or 30% wDDGS were formulated to meet or
      exceed the nutrient requirements of the Hybrid Converter female turkeys. The 30%
      wDDGS diet was substituted with either non-extruded (EX-) or extruded (EX+) wDDGS
      to produce three basal diets [0% wDDGS (EX-) or 30% wDDGS (EX-/EX+)]. Diets were
      blended to obtain 15% wDDGS. In the respective treatments, only wDDGS was
      extruded (temperature; 118 degrees C, retention; 15 sec, total moisture; 25% and
      pressure 33 bar). The respective experimental diets were supplemented
      with/without an enzyme cocktail (E; 0.5 g/kg). Test diets were fed from 7-21 d in
      a completely randomized design. In Experiment 1, a total of 210 turkey hen poults
      were fed diets containing 0, 15, or 30% wDDGS (EX-) with or without enzyme (E+/E
      ). Body weight (BW) and feed intake (FI) were significantly higher for 0% wDDGSE
      . Nitrogen retention (NR) and apparent metabolizable energy (AME) for the 30%
      wDDGSE- was significantly higher than other treatments at 21 d. The results
      indicated significant main effects of E and an interaction between wDDGS level
      and E. In Experiment 2, 280 turkey hen poults were fed 8 diets [15/30% wDDGS
      (E+/E-), (EX-/EX+)]. The level of wDDGS had a significant effect on BW, FI and
      gain:feed; 15% inclusion was superior to 30%. There were significant 2- and 3-way
      interactions for AME and NR at 21 d due to differences in enzyme response with 15
      or 30% wDDGS inclusion and/or extrusion of wDDGS. As high as 15% wDDGS can be
      incorporated in turkey hen diets. There were no beneficial effects of EX or E on
      poult performance. 

PMID- 25595483
TI  - Current adjuvant therapeutic approaches for pancreatic cancer.
AB  - Pancreatic cancer continues to be the fourth leading cause of death despite
      advancements in surgical and adjuvant therapeutic approaches. In the present
      review, the current cytotoxic therapeutic approaches and advanced targeted
      therapies are objectively discussed with consideration to the current literature.

PMID- 25595484
TI  - A dual strategy for sensing metals with a nano 'pincer' scavenger for in vitro
      diagnostics and detection of liver diseases from blood samples.
AB  - This work presents a dual, non-invasive approach for the detection of elevated
      level of metals in patients with liver disease. A highly sensitive, small
      molecule 'pincer' scavenger was synthesized for the detection and quantification
      of copper in serum and systemically in vivo. For the in vitro diagnostics, the
      developed technique involves only a routine capillary blood sampling or
      venipuncture, removing the need for invasive biopsies. The organic scavenger
      molecule showed high specificity toward copper ions, with a detection sensitivity
      of 1.35 * 10(-2)MUg/L in mouse serum. Furthermore, for the systemic detection of
      copper in the liver, a polymeric nanopincer has been designed and studied. The
      small molecule scavengers were stably incorporated into polymeric micelles via
      its long acyl chains and polymeric micelle proved to be a stable carrier when
      injected into mice intravenously. The organic scavenger molecule was found to be
      highly fluorescent and specific toward Cu(2+) and can potentially help ameliorate
      diseases regarding accretion of copper in certain vital organs. The strategy and
      the results provide a novel, non-invasive dual nanomedicine approach for the
      early detection and treatment of excessive metal deposits in the human organs.

PMID- 25595485
TI  - Endocannabinoid-mediated modulation of Gq/11 protein-coupled receptor signaling
      induced vasoconstriction and hypertension.
AB  - Activation of G protein-coupled receptors (GPCRs) can induce vasoconstriction via
      calcium signal-mediated and Rho-dependent pathways. Earlier reports have shown
      that diacylglycerol produced during calcium signal generation can be converted to
      an endocannabinoid, 2-arachidonoylglycerol (2-AG). Our aim was to provide
      evidence that GPCR signaling-induced 2-AG production and activation of vascular
      type1 cannabinoid receptors (CB1R) is capable of reducing agonist-induced
      vasoconstriction and hypertension. Rat and mouse aortic rings were examined by
      myography. Vascular expression of CB1R was demonstrated with
      immunohistochemistry. Rat aortic vascular smooth muscle cells (VSMCs) were
      cultured for calcium measurements and 2-AG-determination. Inhibition or genetic
      loss of CB1Rs enhanced vasoconstriction induced by angiotensin II (AngII) or
      phenylephrine (Phe), but not by prostaglandin(PG)F2alpha. AngII-induced
      vasoconstriction was augmented by inhibition of diacylglycerol lipase
      (tetrahydrolipstatin) and was attenuated by inhibition of monoacylglycerol lipase
      (JZL184) suggesting a functionally relevant role for endogenously produced 2-AG.
      In Galphaq/11-deficient mice vasoconstriction was absent to AngII or Phe, which
      activate Gq/11-coupled receptors, but was maintained in response to PGF2alpha. In
      VSMCs, AngII-stimulated 2-AG-formation was inhibited by tetrahydrolipstatin and
      potentiated by JZL184. CB1R inhibition increased the sustained phase of AngII
      induced calcium signal. Pharmacological or genetic loss of CB1R function
      augmented AngII-induced blood pressure rise in mice. These data demonstrate that
      vasoconstrictor effect of GPCR agonists is attenuated via Gq/11-mediated vascular
      endocannabinoid formation. Agonist-induced endocannabinoid-mediated CB1R
      activation is a significant physiological modulator of vascular tone. Thus, the
      selective modulation of GPCR signaling-induced endocannabinoid release has a
      therapeutic potential in case of increased vascular tone and hypertension. 

PMID- 25595486
TI  - Inhibition of prolyl hydroxylase 3 ameliorates cardiac dysfunction in diabetic
      cardiomyopathy.
AB  - Prolyl hydroxylase 3 (PHD3) is a member of the prolyl hydroxylases (PHDs) family
      and is induced by hypoxia. It plays a critical role in regulating the abundance
      of hypoxia-inducible factor (HIF). Its expression is increased in diabetic rat
      hearts; however, its role remains unclear. We investigated the potential role and
      mechanism of action of PHD3 in the setting of diabetes-induced myocardial
      dysfunction in rats. In vivo, type 2 diabetic rat model was induced via a high
      fat diet and intraperitoneal injection of streptozotocin. PHD3 expression was
      knocked down using lentivirus-mediated short-hairpin RNA (shRNA). In vitro,
      primary neonatal cardiomyocytes and H9c2 cardiomyoblasts were cultured in 33.3 mM
      glucose (high glucose, HG) and 5.5 mM glucose (normal glucose, NG), the latter of
      which was used as a control. PHD3-siRNA was used to inhibit the expression of
      PHD3 and to investigate the role of PHD3 in HG-induced apoptosis in H9c2
      cardiomyoblasts. Rats with diabetic cardiomyopathy (DCM) exhibited severe left
      ventricular dysfunction as well as myocardial apoptosis and fibrosis. PHD3
      expression was increased in the myocardial tissues of diabetic rats, and
      inhibition of PHD3 ameliorated the disease. Additionally, the inhibition of PHD3
      significantly decreased HG-induced apoptosis and MAPK activation in H9c2
      cardiomyoblasts. Our results suggest that PHD3 inhibition ameliorates myocardial
      dysfunction in the setting of diabetic cardiomyopathy. 

PMID- 25595488
TI  - Short-term dynamics of cyanobacterial toxins (microcystins) following a discharge
      from a coastal reservoir in Isahaya Bay, Japan.
AB  - Freshwater cyanobacteria produce highly toxic substances such as microcystins
      (MCs), and water containing MCs is often discharged to downstream and coastal
      areas. We conducted field monitoring in Isahaya Bay to clarify the short-term
      dynamics of MCs discharged from a reservoir following a cyanobacteria bloom in
      the warm season. MCs were detected in the seawater of the bay (max. 0.10 MUg L(
      1)), and were deposited on the sea floor, with the MC content of the surface
      sediment increasing by approximately five times (0.11+/-0.077-0.53+/-0.15 MUg
      kgww(-1), mean+/-SD) at the four stations near the reservoir drainage gate before
      and after the discharge. The MCs was then transported from the mouth of the bay
      by tidal currents during the period of the study. Therefore, the MCs were moved
      away from the closed water area where the cyanobacteria blooms, and spread
      throughout the coastal area.

PMID- 25595487
TI  - Workplace violence against homecare workers and its relationship with workers
      health outcomes: a cross-sectional study.
AB  - BACKGROUND: Consumer-driven homecare models support aging and disabled
      individuals to live independently through the services of homecare workers.
      Although these models have benefits, including autonomy and control over
      services, little evidence exists about challenges homecare workers may face when
      providing services, including workplace violence and the negative outcomes
      associated with workplace violence. This study investigates the prevalence of
      workplace violence among homecare workers and examines the relationship between
      these experiences and homecare worker stress, burnout, depression, and sleep.
      METHODS: We recruited female homecare workers in Oregon, the first US state to
      implement a consumer driven homecare model, to complete an on-line or telephone
      survey with peer interviewers. The survey asked about demographics and included
      measures to assess workplace violence, fear, stress, burnout, depression and
      sleep problems. RESULTS: Homecare workers (n = 1,214) reported past-year
      incidents of verbal aggression (50.3% of respondents), workplace aggression
      (26.9%), workplace violence (23.6%), sexual harassment (25.7%), and sexual
      aggression (12.8%). Exposure was associated with greater stress (p < .001),
      depression (p < .001), sleep problems (p < .001), and burnout (p < .001).
      Confidence in addressing workplace aggression buffered homecare workers against
      negative work and health outcomes. CONCLUSIONS: To ensure homecare worker safety
      and positive health outcomes in the provision of services, it is critical to
      develop and implement preventive safety training programs with policies and
      procedures that support homecare workers who experience harassment and violence.

PMID- 25595489
TI  - Favored use of anti-predator netting (APN) applied for the farming of clams leads
      to little benefits to industry while increasing nearshore impacts and plastics
      pollution.
AB  - An overview of the efficacy of anti-predator netting (APN) used by the shellfish
      industry is presented. There is little support that the currently favored APN
      effectively protects farmed clams from predators. Evidence does suggest that APN
      leads to impacts and pollution. APN is an attractant for predators, e.g., crabs,
      by providing a refuge within Ulva sp. which attaches onto the surface of APN. APN
      entrains silt and organic matter and increases sediment temperatures degrading
      habitat underneath the APN. APN present hazards to fish and wildlife and is a
      source of plastics to the marine environment. The continued use of ineffective
      APN does not serve either the environment or industry well, and many of these
      issues could be addressed through the alternate use of "ancient" technology used
      by aboriginal people to maintain clam gardens; building of rock walls optimizing
      the amount of clam habitat thereby increasing numbers without the use of APN. 

PMID- 25595490
TI  - Maternal transfer of organohalogenated compounds in sharks and stingrays.
AB  - Elasmobranchs can bioaccumulate considerable amounts of persistent organic
      pollutants (POPs) and utilize several reproductive strategies thereby influencing
      maternal transfer of contaminants. This study provides preliminary data on the
      POP transfer from pregnant females to offspring of three species (Atlantic
      stingrays, bonnethead, blacktip sharks) with different reproduction modes
      (aplacental, placental viviparity). Polychlorinated biphenyl (PCB) levels were
      generally higher than any other POPs. Stingrays and blacktip shark embryos
      contained the lowest POP concentrations while bonnetheads and the blacktip adult
      female had the highest concentrations. Results suggest that POPs are more readily
      transferred from the mother to the embryo compared to what is transferred to ova
      in stingrays. Statistically significant differences in levels of selected POPs
      were found between embryos from the left and right uterus within the same litter
      as well as between female and male embryos within the same litter for
      bonnetheads, but not for the blacktip sharks. 

PMID- 25595492
TI  - Combined photon-electron beams in the treatment of the supraclavicular lymph
      nodes in breast cancer: A novel technique that achieves adequate coverage while
      reducing lung dose.
AB  - Radiation pneumonitis is a well-documented side effect of radiation therapy for
      breast cancer. The purpose of this study was to compare combined photon-electron,
      photon-only, and electron-only plans in the radiation treatment of the
      supraclavicular lymph nodes. In total, 13 patients requiring chest wall and
      supraclavicular nodal irradiation were planned retrospectively using combined
      photon-electron, photon-only, and electron-only supraclavicular beams. A dose of
      50Gy over 25 fractions was prescribed. Chest wall irradiation parameters were
      fixed for all plans. The goal of this planning effort was to cover 95% of the
      supraclavicular clinical target volume (CTV) with 95% of the prescribed dose and
      to minimize the volume receiving >= 105% of the dose. Comparative end points were
      supraclavicular CTV coverage (volume covered by the 95% isodose line), hotspot
      volume, maximum radiation dose, contralateral breast dose, mean total lung dose,
      total lung volume percentage receiving at least 20 Gy (V(20 Gy)), heart volume
      percentage receiving at least 25 Gy (V(25 Gy)). Electron and photon energies
      ranged from 8 to 18 MeV and 4 to 6 MV, respectively. The ratio of photon-to
      electron fractions in combined beams ranged from 5:20 to 15:10. Supraclavicular
      nodal coverage was highest in photon-only (mean = 96.2 +/- 3.5%) followed closely
      by combined photon-electron (mean = 94.2 +/- 2.5%) and lowest in electron-only
      plans (mean = 81.7 +/- 14.8%, p < 0.001). The volume of tissue receiving >= 105%
      of the prescription dose was higher in the electron-only (mean = 69.7 +/- 56.1
      cm(3)) as opposed to combined photon-electron (mean = 50.8 +/- 40.9 cm(3)) and
      photon-only beams (mean = 32.2 +/- 28.1 cm(3), p = 0.114). Heart V(25 Gy) was not
      statistically different among the plans (p = 0.999). Total lung V(20 Gy) was
      lowest in electron-only (mean = 10.9 +/- 2.3%) followed by combined photon
      electron (mean = 13.8 +/- 2.3%) and highest in photon-only plans (mean = 16.2 +/-
      3%, p < 0.001). As expected, photon-only plans demonstrated the highest target
      coverage and total lung V(20 Gy). The superiority of electron-only beams, in
      terms of decreasing lung dose, is set back by the dosimetric hotspots associated
      with such plans. Combined photon-electron treatment is a feasible technique for
      supraclavicular nodal irradiation and results in adequate target coverage,
      acceptable dosimetric hotspot volume, and slightly reduced lung dose.

PMID- 25595493
TI  - Replacement P212H altered the pH-temperature profile of phytase from Aspergillus
      niger NII 08121.
AB  - Microbial phytase, a widely used animal feed enzyme, needs to be active and
      stable in the acidic milieu for better performance in the monogastric gut.
      Aspergillus niger phytases exhibit an activity dip in the pH range from 3.0 to
      3.5. Replacement of amino acids, which changed the pKa of catalytic residues H82
      and D362, resulted in alteration of the pH profile of a thermostable phytase from
      A. niger NII 08121. Substitution P212H in the protein loop at 14 A distance to
      the active site amended the pH optimum from 2.5 to pH 3.2 nevertheless with a
      decrease in thermostability than the wild enzyme. This study described the
      utility of amino acid replacements based on pKa shifts of catalytic acid/base to
      modulate the pH profile of phytases. 

PMID- 25595491
TI  - Comparison of testicular dose delivered by intensity-modulated radiation therapy
      (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with prostate
      cancer.
AB  - A small decrease in testosterone level has been documented after prostate
      irradiation, possibly owing to the incidental dose to the testes. Testicular
      doses from prostate external beam radiation plans with either intensity-modulated
      radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) were
      calculated to investigate any difference. Testicles were contoured for 16
      patients being treated for localized prostate cancer. For each patient, 2 plans
      were created: 1 with IMRT and 1 with VMAT. No specific attempt was made to reduce
      testicular dose. Minimum, maximum, and mean doses to the testicles were recorded
      for each plan. Of the 16 patients, 4 received a total dose of 7800 cGy to the
      prostate alone, 7 received 8000 cGy to the prostate alone, and 5 received 8000
      cGy to the prostate and pelvic lymph nodes. The mean (range) of testicular dose
      with an IMRT plan was 54.7 cGy (21.1 to 91.9) and 59.0 cGy (25.1 to 93.4) with a
      VMAT plan. In 12 cases, the mean VMAT dose was higher than the mean IMRT dose,
      with a mean difference of 4.3 cGy (p = 0.019). There was a small but
      statistically significant increase in mean testicular dose delivered by VMAT
      compared with IMRT. Despite this, it unlikely that there is a clinically
      meaningful difference in testicular doses from either modality.

PMID- 25595494
TI  - Biosensor technology for pesticides--a review.
AB  - Pesticides, due to their lucrative outcomes, are majorly implicated in
      agricultural fields for crop production enhancement. Due to their pest removal
      properties, pesticides of various classes have been designed to persist in the
      environment over a longer duration after their application to achieve maximum
      effectiveness. Apart from their recalcitrant structure and agricultural benefits,
      pesticides also impose acute toxicological effects onto the other various life
      forms. Their accumulation in the living system may prove to be detrimental if
      established in higher concentrations. Thus, their prompt and accurate analysis is
      a crucial matter of concern. Conventional techniques like chromatographic
      techniques (HPLC, GC, etc.) used for pesticides detection are associated with
      various limitations like stumpy sensitivity and efficiency, time consumption,
      laboriousity, requirement of expensive equipments and highly trained technicians,
      and many more. So there is a need to recruit the methods which can detect these
      neurotoxic compounds sensitively, selectively, rapidly, and easily in the field.
      Present work is a brief review of the pesticide effects, their current usage
      scenario, permissible limits in various food stuffs and 21st century advancements
      of biosensor technology for pesticide detection. Due to their exceptional
      performance capabilities, easiness in operation and on-site working, numerous
      biosensors have been developed for bio-monitoring of various environmental
      samples for pesticide evaluation immensely throughout the globe. Till date, based
      on sensing element (enzyme based, antibody based, etc.) and type of detection
      method used (Electrochemical, optical, and piezoelectric, etc.), a number of
      biosensors have been developed for pesticide detection. In present communication,
      authors have summarized 21st century's approaches of biosensor technology for
      pesticide detection such as enzyme-based biosensors, immunosensors, aptamers,
      molecularly imprinted polymers, and biochips technology. Also, the major
      technological advancements of nanotechnology in the field of biosensor technology
      are discussed. Various biosensors mentioned in manuscript are found to exhibit
      storage stability of biocomponent ranging from 30-60 days, detection limit of 10(
      6) - 10(-16) M, response time of 1-20 min and applications of developed
      biosensors in environmental samples (water, food, vegetables, milk, and juice
      samples, etc.) are also discussed. Researchers all over the globe are working
      towards the development of different biosensing techniques based on contrast
      approaches for the detection of pesticides in various environmental samples. 

PMID- 25595495
TI  - Response to commentary by Champ and Klement: Is a ketogenic diet the solution for
      the hyperglycemia problem in glioblastoma therapy?

PMID- 25595496
TI  - Tetrahydroxystilbene glucoside extends mouse life span via upregulating neural
      klotho and downregulating neural insulin or insulin-like growth factor 1.
AB  - A Chinese herb, Polygonatum multiflorum, has been reported to prolong animal life
      span, but the relevant molecular mechanism remains unclear. Tetrahydroxystilbene
      glucoside (TSG) is one main component of P. multiflorum and may contribute to
      extending life span of mammals. On the other hand, neuronal insulin signaling
      mediates the life span of mammals. Therefore, we investigated the effects of TSG
      on memory ability, life span, and the neural insulin signaling in the senescence
      accelerated prone mouse (SAMP8). TSG improved the memory ability significantly (p
      < 0.01, compared with a control group). TSG prolonged the life span of SAMP8 by
      17% at the most (p < 0.01, compared with a control group). TSG increased the
      protein level of neural klotho and reduced the levels of neural insulin, insulin
      receptor, insulin-like growth factor-1, and insulin-like growth factor-1 receptor
      in the brain of SAMP8 (p < 0.01, compared with a control group). All these
      proteins are key factors of the pathways related to neural insulin/IGF-1
      signaling. These findings suggest that TSG has anti-aging effects on mammals.
      From these results, TSG from P. multiflorum should be developed as a potential
      anti-age drug. 

PMID- 25595497
TI  - Aneuploidy in Lewy body diseases.
AB  - An increase in DNA content is associated with neuronal degeneration in
      Alzheimer's disease but has not been evaluated in Lewy body diseases. Using
      stereological principles, flow cytometry, and standard histopathologic methods,
      we evaluated the number and DNA content of neurons and all cells and the severity
      of Lewy and Alzheimer pathologies, in brain regions affected at different stages
      in Lewy body diseases compared with controls. An increase in neuronal DNA content
      was observed in all the affected brain regions examined, although this change was
      related to different pathologies. In the substantia nigra, increased neuronal DNA
      content related to neuronal loss, whereas in the cortex and hippocampus,
      increased neuronal DNA content related to Alzheimer pathologies. Of note,
      increased neuronal DNA content did not relate to the deposition of Lewy bodies in
      any region examined. These data support the concept that increased DNA content
      increases neuronal susceptibility to degeneration and Alzheimer pathologies. 

PMID- 25595498
TI  - Identification of PSEN1 mutations p.M233L and p.R352C in Han Chinese families
      with early-onset familial Alzheimer's disease.
AB  - Early-onset familial Alzheimer's disease (EOFAD) is characterized by the onset of
      dementia symptoms before 65 years, positive family history, high genetic
      predisposition, and an autosomal dominant inheritance. We aimed to investigate
      mutations and to characterize phenotypes in Chinese EOFAD families. Detailed
      clinical assessments and genetic screening for mutations in the presenilin 1
      (PSEN1), presenilin 2, amyloid precursor protein, and APOE genes were carried out
      in 4 EOFAD families. Two PSEN1 mutations (p.R352C and p.M233L) were identified in
      2 EOFAD families, respectively. Mutation p.M233L was associated with prominent
      very early onset, rapidly progressive dementia, and neurologic symptoms, whereas
      p.R352C was associated with a progressive dementia, psychiatric syndrome, and
      chronic disease course. Both mutations are predicted to be pathogenic. Our
      results showed that mutations in PSEN1 gene might be common in Chinese EOFAD
      families.

PMID- 25595500
TI  - Attentional load modulates large-scale functional brain connectivity beyond the
      core attention networks.
AB  - In line with the notion of a continuously active and dynamic brain, functional
      networks identified during rest correspond with those revealed by task-fMRI.
      Characterizing the dynamic cross-talk between these network nodes is key to
      understanding the successful implementation of effortful cognitive processing in
      healthy individuals and its breakdown in a variety of conditions involving
      aberrant brain biology and cognitive dysfunction. We employed advanced network
      modeling on fMRI data collected during a task involving sustained attentive
      tracking of objects at two load levels and during rest. Using multivariate
      techniques, we demonstrate that attentional load levels can be significantly
      discriminated, and from a resting-state condition, the accuracy approaches 100%,
      by means of estimates of between-node functional connectivity. Several network
      edges were modulated during task engagement: The dorsal attention network
      increased connectivity with a visual node, while decreasing connectivity with
      motor and sensory nodes. Also, we observed a decoupling between left and right
      hemisphere dorsal visual streams. These results support the notion of dynamic
      network reconfigurations based on attentional effort. No simple correspondence
      between node signal amplitude change and node connectivity modulations was found,
      thus network modeling provides novel information beyond what is revealed by
      conventional task-fMRI analysis. The current decoding of attentional states
      confirms that edge connectivity contains highly predictive information about the
      mental state of the individual, and the approach shows promise for the
      utilization in clinical contexts. 

PMID- 25595501
TI  - Effect of an 8-week practice of externally triggered speech on basal ganglia
      activity of stuttering and fluent speakers.
AB  - The neural mechanisms underlying stuttering are not well understood. It is known
      that stuttering appears when persons who stutter speak in a self-paced manner,
      but speech fluency is temporarily increased when they speak in unison with
      external trigger such as a metronome. This phenomenon is very similar to the
      behavioral improvement by external pacing in patients with Parkinson's disease.
      Recent imaging studies have also suggested that the basal ganglia are involved in
      the etiology of stuttering. In addition, previous studies have shown that the
      basal ganglia are involved in self-paced movement. Then, the present study
      focused on the basal ganglia and explored whether long-term speech-practice using
      external triggers can induce modification of the basal ganglia activity of
      stuttering speakers. Our study of functional magnetic resonance imaging revealed
      that stuttering speakers possessed significantly lower activity in the basal
      ganglia than fluent speakers before practice, especially when their speech was
      self-paced. After an 8-week speech practice of externally triggered speech using
      a metronome, the significant difference in activity between the two groups
      disappeared. The cerebellar vermis of stuttering speakers showed significantly
      decreased activity during the self-paced speech in the second compared to the
      first experiment. The speech fluency and naturalness of the stuttering speakers
      were also improved. These results suggest that stuttering is associated with
      defective motor control during self-paced speech, and that the basal ganglia and
      the cerebellum are involved in an improvement of speech fluency of stuttering by
      the use of external trigger. 

PMID- 25595499
TI  - Small deletion in C9orf72 hides a proportion of expansion carriers in FTLD.
AB  - Frontotemporal lobar degeneration is a highly familial disease and the most
      common known genetic cause is the repeat expansion mutation in the gene C9orf72.
      We have identified 2 brothers with an expansion mutation in C9orf72 using
      Southern blotting that is undetectable using repeat-primed polymerase chain
      reaction. Sequencing using high concentrations of DNA denaturants of a bacterial
      artificial chromosome clone obtained from one of the brothers identified a 10
      base pair deletion adjacent to the expansion that presumably confers strong
      secondary structure that interferes with the genotyping. Using an alternative
      method, we have identified missed expansion carriers in our cohort, and this
      number has increased by approximately 25%. This observation has important
      implications for patients undergoing genetic testing for C9orf72. 

PMID- 25595502
TI  - A human post-mortem brain model for the standardization of multi-centre MRI
      studies.
AB  - Multi-centre MRI studies of the brain are essential for enrolling large and
      diverse patient cohorts, as required for the investigation of heterogeneous
      neurological and psychiatric diseases. However, the multi-site comparison of
      standard MRI data sets that are weighted with respect to tissue parameters such
      as the relaxation times (T1, T2) and proton density (PD) may be problematic, as
      signal intensities and image contrasts depend on site-specific details such as
      the sequences used, imaging parameters, and sensitivity profiles of the
      radiofrequency (RF) coils. Water or gel phantoms are frequently used for long
      term and/or inter-site quality assessment. However, these phantoms hardly mimic
      the structure, shape, size or tissue distribution of the human brain. The goals
      of this study were: (1) to validate the long-term stability of a human post
      mortem brain phantom, performing quantitative mapping of T1, T2, and PD, and the
      magnetization transfer ratio (MTR) over a period of 18months; (2) to acquire and
      analyse data for this phantom and the brain of a healthy control (HC) in a multi
      centre study for MRI protocol standardization in four centres, while conducting a
      voxel-wise as well as whole brain grey (GM) and white matter (WM) tissue volume
      comparison. MTR, T2, and the quotient of PD in WM and GM were stable in the post
      mortem brain with no significant changes. T1 was found to decrease from 267/236ms
      (GM/WM) to 234/216ms between 5 and 17weeks post embedment, stabilizing during an
      18-month period following the first scan at about 215/190ms. The volumetric
      measures, based on T1-weighted MP-RAGE images obtained at all participating
      centres, revealed inter- and intra-centre variations in the evaluated GM and WM
      volumes that displayed similar trends in both the post-mortem brain as well as
      the HC. At a confidence level of 95%, brain regions such as the brainstem, deep
      GM structures as well as boundaries between GM and WM tissues were found to be
      less reproducible than other brain regions in all participating centres. The
      results demonstrate that a post-mortem brain phantom may be used as a reliable
      tool for multi-centre MR studies. 

PMID- 25595503
TI  - Microscopic diffusion anisotropy in the human brain: reproducibility, normal
      values, and comparison with the fractional anisotropy.
AB  - Human neuroimaging of tissue microstructure, such as axonal density and
      integrity, is key in clinical and neuroscience research. Most studies rely on
      diffusion tensor imaging (DTI) and the measures derived from it, most prominently
      fractional anisotropy (FA). However, FA also depends on fiber orientation
      distribution, a more macroscopic tissue property. Recently introduced measures of
      so-called microscopic diffusion anisotropy, diffusion anisotropy on a cellular or
      microscopic level, overcome this limitation because they are independent of the
      orientation distributions of axons and fibers. In this study, we evaluate the
      feasibility of two measures of microscopic diffusion anisotropy I(MA) and MA
      indices, for human neuroscience and clinical research. Both indices reflect the
      eccentricity of the cells but while I(MA) also depends on the cell size, MA is
      independent of the cell size and, like FA, scaled between 0 and 1. In whole-brain
      measurements of a group of 19 healthy volunteers, we measured average values and
      variability, evaluated their reproducibility, both within and between sessions,
      and compared MA to FA values in selected regions-of-interest (ROIs). The within-
      and between-session comparison did not show substantial differences but the
      reproducibility was much better for the MA than I(MA) (coefficient of variation
      between sessions 10.5% vs. 28.9%). The reproducibility was less for MA than FA
      overall, but comparable in the defined ROIs and the average group sizes required
      for between-group comparisons was similar (about 60 participants for a relative
      difference of 5%). Group-averaged values of MA index were generally larger and
      showed less variation across white-matter brain ROIs than FA (mean +/- standard
      deviation of seven ROIs 0.83 +/- 0.10 vs. 0.58 +/- 0.13). Even in some gray
      matter ROIs, MA values comparable to those of white matter ROIs were observed.
      Furthermore, the within-group variation of the values in white matter ROIs was
      lower for the MA compared to the FA (mean standard deviation over volunteers
      0.038 vs. 0.049) which could be due to significant variability in the
      distribution of fiber orientation contributing to FA. These results indicate that
      MA (i) should be preferred to I(MA), (ii) has a reproducibility and group-size
      requirements comparable to those of FA; (iii) is less sensitive to the fiber
      orientation distribution than FA; and (iv) could be more sensitive to differences
      or changes of the tissue microstructure than FA. R1.1.

PMID- 25595504
TI  - Environmental enrichment is associated with rapid volumetric brain changes in
      adult mice.
AB  - Environmental enrichment is a model of increased structural brain plasticity.
      Previous histological observations have shown molecular and cellular changes in a
      few pre-determined areas of the rodent brain. However, little is known about the
      time course of enrichment-induced brain changes and how they distribute across
      the whole brain. Here we expose adult mice to three weeks of environmental
      enrichment using a novel re-configurable maze design. In-vivo MRI shows
      volumetric brain changes in brain areas related to spatial memory, navigation,
      and sensorimotor experience, such as the hippocampal formation and the
      sensorimotor cortex. Evidence from a second cohort of mice indicates that these
      plastic changes might occur as early as 24h after exposure. This suggests that
      novel experiences are powerful modulators of plasticity even in the adult brain.
      Understanding and harnessing the underlying molecular mechanisms could advance
      future treatments of neurological disease. 

PMID- 25595505
TI  - Towards brain-activity-controlled information retrieval: Decoding image relevance
      from MEG signals.
AB  - We hypothesize that brain activity can be used to control future information
      retrieval systems. To this end, we conducted a feasibility study on predicting
      the relevance of visual objects from brain activity. We analyze both
      magnetoencephalographic (MEG) and gaze signals from nine subjects who were
      viewing image collages, a subset of which was relevant to a predetermined task.
      We report three findings: i) the relevance of an image a subject looks at can be
      decoded from MEG signals with performance significantly better than chance, ii)
      fusion of gaze-based and MEG-based classifiers significantly improves the
      prediction performance compared to using either signal alone, and iii) non-linear
      classification of the MEG signals using Gaussian process classifiers outperforms
      linear classification. These findings break new ground for building brain
      activity-based interactive image retrieval systems, as well as for systems
      utilizing feedback both from brain activity and eye movements. 

PMID- 25595506
TI  - Reality TV and vicarious embarrassment: an fMRI study.
AB  - BACKGROUND: Vicarious embarrassment (VE) is an emotion triggered by the
      observation of others' pratfalls or social norm violations. Several explanatory
      approaches have been suggested to explain the source of this phenomenon,
      including perspective taking abilities or ingroup identification. Knowledge about
      its biological bases, however, is scarce. To gain a better understanding, the
      present study investigated neural activation patterns in response to video clips
      from reality TV shows. Reality TV is well known for presenting social norm
      violations, flaws and pratfalls of its protagonists in real life situations
      thereby qualifying as an ecological valid trigger for VE. METHODS: N = 60 healthy
      participants viewed stand stills from previously watched video clips taken from
      German reality TV-shows while undergoing functional magnetic resonance imaging.
      The clips were preselected for high versus low VE content in a pilot study.
      Besides the investigation of differences in brain activation elicited by VE
      versus control stand stills (blocked design contrast), we performed additional
      exploratory functional connectivity analyses (psychophysiological interaction;
      PPI) to detect VE related brain networks. RESULTS: Compared to the low VE
      condition, participants in the high VE condition showed a higher activation in
      the middle temporal gyrus, the supramarginal gyrus, the right inferior frontal
      gyrus and the gyrus rectus. Functional connectivity analyses confirmed increased
      connectivity of these regions with the anterior cingulate in the VE condition.
      Moreover, self-ratings of VE and brain activity were correlated positively.
      CONCLUSION: Reality TV formats with high VE content activate brain regions
      associated with Theory of Mind, but also with empathic concern and social
      identity. Therefore, our results support the idea that the ability to put oneself
      in other person's shoes is a major prerequisite for VE.

PMID- 25595507
TI  - Flow-volume loop: window to a smooth diagnosis?

PMID- 25595508
TI  - Ethics, consent and blinding: lessons from a placebo/sham controlled CPAP
      crossover trial.
AB  - INTRODUCTION: Performing rigorously designed clinical trials in device-based
      treatments is challenging. Continuous positive airway pressure (CPAP) is the most
      effective device-based treatment for obstructive sleep apnoea. We performed a
      randomised crossover trial of CPAP versus placebo therapy and did not disclose
      the presence of placebo. We assessed rates of staff unblinding, the likelihood of
      patient unblinding and obtained patient perceptions on lack of full disclosure.
      METHODS: All patients (n=30) underwent a semi-structured exit interview. Prior to
      full disclosure patients were asked questions to ascertain whether they suspected
      one therapy was ineffective. The use of placebo was then disclosed and additional
      questions were administered to indicate the likelihood of unblinding had full
      disclosure occurred during consent. Staff unblinding was determined by means of a
      questionnaire that was completed after each patient encounter. RESULTS: While the
      lack of full disclosure prevented patient unblinding during the trial, patients
      revealed a clear preference for active CPAP. After disclosing the presence of
      placebo, 73% (n=22) felt they would have been unblinded had they known at the
      start of the trial. Only one patient described unease about the lack of full
      disclosure. Staff thought they were unblinded in 6% (n=16/282) of encounters.
      They correctly identified the treatment device in 69% of cases (n=11/16,
      p<0.001). CONCLUSIONS: Successful patient blinding was achieved, however this was
      probably reliant on the lack of full disclosure. Staff unblinding occurred and
      highlights the difficulty with investigator blinding in device-based trials.
      Ethical challenges in this type of study are likely to compromise research
      feasibility. TRIAL REGISTRATION NUMBER: This clinical trial is registered with
      the Australian and New Zealand Clinical Trials Registry at
      http://www.anzctr.org.au (ACTRN 12605000066684).

PMID- 25595509
TI  - Quality assurance in melanoma surgery: The evolving experience at a large
      tertiary referral centre.
AB  - BACKGROUND: The quality of melanoma surgery needs to be assessed by oncological
      outcome and complication rates. There is no published consensus on complication
      rates for common melanoma surgeries, namely wide excision (WE), sentinel node
      biopsy (SNB) and regional lymph node dissection (RLND). Consequently there are no
      agreed standards by which surgeons can audit their practices. METHODS: Surgical
      standards were proposed in 2008 following review of the literature and from
      expert opinion. Melanoma Institute Australia (MIA) self-reported audit data from
      2011 and 2012 were compared with these standards. To quality check the self
      reported audit, RLND data were extracted from the MIA database. RESULTS: Six
      surgeons performed a mean of 568 surgeries each quarter; with a mean of 106 major
      procedures. Following WE with primary closure or flap repair, wound infection or
      dehiscence occurred in <1% of cases. When skin grafting was required non-take of
      >20% of the grafted area was observed in 5.9% of cases. Following SNB wound
      infection and significant seroma occurred in 1.8% of cases. RLND node counts were
      below the 90% standard in 4 of 409 procedures. In comparison, data extraction
      identified 405 RLNDs, with node counts below the 90% standard in eight
      procedures. Two of these patients had previously undergone surgery removing nodes
      from the field and two had gross coalescing disease with extensive extra-nodal
      spread. CONCLUSION: The quality standards proposed in 2008 have been validated
      long-term by high volume caseloads. The data presented provide standards by which
      melanoma surgeons can audit their surgical performance.

PMID- 25595510
TI  - Nosocomial pneumonia caused by carbapenem-resistant Raoultella planticola: a case
      report and literature review.
AB  - Raoultella planticola is a rare opportunistic pathogen usually invaded
      immunocompromised patients and sometimes even causes fatal infections. Recently,
      there is growing concern about the emergence of carbapenem resistance in this
      species. Here, we describe one case of hospital-acquired pneumonia due to a
      carbapenem-resistant R. planticola (CRRP) co-producing Klebsiella pneumoniae
      carbapenemase and extended-spectrum beta-lactamase. A literature review was
      performed to indicate the microbiological and clinical features of infections
      caused by CRRP. 

PMID- 25595511
TI  - Design and development of a content-based medical image retrieval system for
      spine vertebrae irregularity.
AB  - BACKGROUND: Content-based medical image retrieval (CBMIR) system enables medical
      practitioners to perform fast diagnosis through quantitative assessment of the
      visual information of various modalities. METHODS: In this paper, a more robust
      CBMIR system that deals with both cervical and lumbar vertebrae irregularity is
      afforded. It comprises three main phases, namely modelling, indexing and
      retrieval of the vertebrae image. The main tasks in the modelling phase are to
      improve and enhance the visibility of the x-ray image for better segmentation
      results using active shape model (ASM). The segmented vertebral fractures are
      then characterized in the indexing phase using region-based fracture
      characterization (RB-FC) and contour-based fracture characterization (CB-FC).
      Upon a query, the characterized features are compared to the query image.
      Effectiveness of the retrieval phase is determined by its retrieval, thus, we
      propose an integration of the predictor model based cross validation neural
      network (PMCVNN) and similarity matching (SM) in this stage. The PMCVNN task is
      to identify the correct vertebral irregularity class through classification
      allowing the SM process to be more efficient. Retrieval performance between the
      proposed and the standard retrieval architectures are then compared using
      retrieval precision (Pr@M) and average group score (AGS) measures. RESULTS:
      Experimental results show that the new integrated retrieval architecture performs
      better than those of the standard CBMIR architecture with retrieval results of
      cervical (AGS > 87%) and lumbar (AGS > 82%) datasets. CONCLUSIONS: The proposed
      CBMIR architecture shows encouraging results with high Pr@M accuracy. As a
      result, images from the same visualization class are returned for further used by
      the medical personnel.

PMID- 25595512
TI  - Long-term results of surgical angioplasty for left main coronary artery stenosis:
      18-year follow-up.
AB  - BACKGROUND: The aim of this study was to determine the long-term outcomes of
      surgical angioplasty for left main coronary artery (SA-LMCA) stenosis. METHODS:
      We retrospectively analyzed data from 24 consecutive patients (mean age, 55
      years; male/female, 12/12) who underwent a surgical angioplasty for the left main
      coronary artery (LMCA) stenosis at our institution between 1995 and 2002. We used
      autologous pericardium in 7 patients and bovine pericardium in 17 patients as a
      patch. We evaluated the late mortality and major adverse cardiac events (MACE)
      rate. RESULTS: There was no operative mortality. Control coronary angiography
      exhibited wide open and funnel-shaped LMCA in all patients. One patient was lost
      to follow-up. During the mean follow-up of 167 months, there were 3 sudden
      cardiac deaths, 4 non-cardiac related deaths, and 9 MACE with one death at
      reoperation. The Kaplan-Meier method identified freedom from cardiac death in
      95.7, 87.0, and 82.4% of the patients, and freedom from MACE in 91.3, 69.6, and
      57.7% of the patients at 5, 10, and 15 years, respectively. CONCLUSIONS: This
      study demonstrated that the long-term outcomes of SA-LMCA with a pericardial
      patch are acceptable compared to those of coronary artery bypass grafting,
      despite the controversy over the indications and the patch material used.

PMID- 25595513
TI  - Sentinel lymph node biopsy in paediatric melanoma. A case series.
AB  - The incidence of melanoma in children is uncommon, being particularly rare in
      children under 10 years-old. However, this disease is increasing by a mean of 2%
      per year. As in adults, the lymph node status is the most important prognostic
      factor, crucial to performing the selective sentinel lymph node biopsy (SLNB). We
      report 3 cases of paediatric patients of 3, 4 and 8 years-old, in which SLNB was
      performed for malignant melanoma. Paediatric age implies greater technical
      difficulty to the scintigraphy scan due to poor patient cooperation, with mild
      sedation required in some cases, and only being able to acquire planar images in
      other cases. SPECT/CT was only performed in the oldest patient. In our cases,
      SLNB was useful for selecting the least invasive surgery in order to reduce
      morbidity. 

PMID- 25595514
TI  - Elbow defect coverage using a capillary perforator flap arising from the vasa
      nervosum of the ulnar nerve.

PMID- 25595515
TI  - Merkel cell carcinoma in East Yorkshire: A case series and literature review of
      current management.
AB  - INTRODUCTION: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine
      tumour of the skin. The incidence is rising and it is associated with sun
      exposure and immunosuppression. Our aim was to perform a 10-year retrospective
      review of MCC treated in East Yorkshire and to examine disease progression,
      surgical and adjuvant management, and outcomes. METHODS: A 10-year retrospective
      review was undertaken of patients identified through the histopathology database.
      Case notes and digital patient records were examined for patient demographics,
      disease characteristics, management and outcome. Disease stage was calculated
      using the 2010 AJCC TNM classification. RESULTS: Thirty-seven patients with
      complete records were included. Twenty-one patients were male and 16 female, with
      mean age 76.7 years at presentation. Pre-malignant or malignant skin changes were
      documented in 15 patients, and immunosuppression in 15 patients. Mean duration of
      lesion was 17.5 weeks. Following diagnosis 22/37 patients underwent further
      surgery with 11 patients undergoing sentinel lymph node (LN) biopsy. LN disease
      was palpable at presentation in 8 patients. Three year survival is 40%.
      CONCLUSIONS: There is no standardised management of MCC and randomised trials are
      challenging due to relatively small numbers. There has been little progress made
      in terms of improving survival. Development of a national database for patients
      with this condition would allow prospective data collection and more accurate
      assessment of current treatment protocols and their efficacy. LEVEL OF EVIDENCE:
      IV.

PMID- 25595516
TI  - Evaluation of the perforator CT-angiography with a cancer risk assessment in DIEP
      flap breast reconstruction.

PMID- 25595517
TI  - Character profiles and life satisfaction.
AB  - BACKGROUND: There is a surge of interest in subjective well-being (SWB), which
      concerns how individuals feel about their happiness. Life satisfaction tends to
      be influenced by individual psychological traits and external social factors. The
      aim of this study was to examine the relationship between individual character
      and SWB. METHODS: Data from 3522 university students were analyzed in this study.
      Character profiles were evaluated using the Temperament and Character Inventory
      Revised Short version (TCI-RS). Life satisfaction was assessed using the
      Satisfaction with Life Scale (SWLS). All statistical tests regarding the
      correlations between each character profile and life satisfaction were conducted
      using ANOVAs, t-tests, multiple linear regression models and correlation
      analyses. RESULTS: The creative (SCT) profile was associated with the highest
      levels of life satisfaction, whereas the depressive (sct) profile was associated
      with the lowest levels of life satisfaction. Additionally, high self
      directedness, self-transcendence and cooperation were associated with high life
      satisfaction. The results of gender-adjusted multiple regression analysis showed
      that the effects of self-directedness were the strongest in the assessment of
      one's quality of life, followed by self-transcendence and cooperativeness, in
      that order. All of the three-character profiles were significantly correlated
      with one's quality of life, and the character profiles of TCI-RS explained 27.6%
      of life satisfaction in total. Among the three-character profiles, the self
      directedness profile was most associated with life satisfaction. LIMITATIONS: Our
      study was cross-sectional, and self-reported data from students at a single
      university were analyzed. CONCLUSIONS: The results of this study showed that,
      among the character profiles, the effects of self-directedness were the strongest
      for predicting life satisfaction.

PMID- 25595518
TI  - Assessment of cigarette smoking status with respect to symptomatic manifestation
      in first-episode schizophrenia patients.
AB  - OBJECTIVE: It has been repeatedly found that cigarette smoking may influence
      schizophrenia psychopathology. However, little is known about the relationship
      between nicotine consumption and symptomatic manifestation of first-episode
      schizophrenia (FES). METHOD: We recruited 109 minimally medicated FES patients.
      Cigarette smoking was assessed using the Fagerstrom test for nicotine dependence
      (FTND) and pack-year index. Psychopathology on the day of recruitment was
      examined using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Smokers
      had significantly lower severity of negative and depressive symptoms in
      comparison with non-smokers. Patients with severe nicotine dependence had
      significantly later age of psychosis onset in comparison with those with mild
      nicotine dependence and non-smokers. Significantly lower severity of negative and
      depressive symptoms was also observed in patients with severe nicotine dependence
      in comparison with non-smokers. The associations between the severity of nicotine
      dependence and scores of negative and depressive symptoms as well as age of
      psychosis onset remained significant after co-varying for gender, education,
      duration of untreated psychosis (DUP) and measures of antipsychotic treatment.
      CONCLUSION: Our results indicate that cigarette smoking might be associated with
      less severe negative and depressive symptoms as well as delayed age of psychosis
      onset. However, longitudinal studies are required to indicate the direction of
      causality.

PMID- 25595519
TI  - Adult separation anxiety differentiates patients with complicated grief and/or
      major depression and is related to lifetime mood spectrum symptoms.
AB  - BACKGROUND: Increasing literature has been focused on complicated grief (CG) and
      its distinctiveness from other potentially loss related mental disorders such as
      major depression (MD). In this regard, symptoms of separation distress seem to
      play a key role. The aim of this study was to compare the clinical features of CG
      to those of MD and of CG+MD, with particular attention to separation anxiety.
      METHODS: Fifty patients with CG (26 with and 24 without MD) and 40 with MD were
      consecutively recruited. Assessments included: SCID-I/P, Inventory of Complicated
      Grief (ICG), Adult Separation Anxiety Symptom Questionnaire (ASA-27), Work and
      Social Adjustment Scale (WSAS), Mood Spectrum-Self Report (MOODS-SR)-lifetime
      version. RESULTS: Patients with MD reported significantly higher ASA-27 scores
      than patients with CG either alone or with MD. In all groups, ASA-27 total scores
      were significantly correlated with the MOODS-SR total scores and with those of
      its depressive component and rhythmicity domain. No significant differences were
      reported in the WSAS scores. LIMITATIONS: Major limitations are the small sample
      size and the use of lifetime instruments. CONCLUSIONS: Our results suggest a
      correlation between adult separation anxiety symptoms and lifetime mood spectrum
      symptoms both in patients with CG and MD. Further studies are needed to better
      understand the role of adult separation anxiety in the development of these
      disorders and for their nosographic autonomy as well.

PMID- 25595521
TI  - [Guidelines in the management of the diabetes mellitus type 2].

PMID- 25595520
TI  - Non-suicidal self-injury and suicidal ideation as predictors of suicide attempts
      in adolescent girls: a multi-wave prospective study.
AB  - Although both suicide ideation (SI) and non-suicidal self-injury (NSSI) are known
      risk factors for suicidal behavior, few longitudinal studies have examined
      whether having a history of one or both of these factors prospectively predicts
      increased risk for suicide attempts. According to the theory of acquired
      capability for suicide, engagement in NSSI may reduce inhibitions around self
      inflicted violence, imparting greater risk for suicide attempts among those with
      SI than would be observed in those with SI who do not have a history of NSSI. We
      used prospective data from the Pittsburgh Girls Study, a large community sample,
      to compare groups of girls reporting no SI or NSSI, SI only, or both NSSI and SI
      between early to late adolescence on any lifetime or recent suicide attempts in
      late adolescence and early adulthood. As compared to girls with no SI or NSSI
      history and those with only an SI history, girls with a history of both NSSI and
      SI were significantly more likely to subsequently report both lifetime and recent
      suicide attempts. Results are consistent with the acquired capability theory for
      suicide and suggest that adolescent girls who have engaged in NSSI and also
      report SI represent a particularly high-risk group in need of prevention and
      intervention efforts. 

PMID- 25595522
TI  - [Hypnic headache, a case report].

PMID- 25595523
TI  - Quantification of ultrasonic texture intra-heterogeneity via volumetric
      stochastic modeling for tissue characterization.
AB  - Intensity variations in image texture can provide powerful quantitative
      information about physical properties of biological tissue. However, tissue
      patterns can vary according to the utilized imaging system and are intrinsically
      correlated to the scale of analysis. In the case of ultrasound, the Nakagami
      distribution is a general model of the ultrasonic backscattering envelope under
      various scattering conditions and densities where it can be employed for
      characterizing image texture, but the subtle intra-heterogeneities within a given
      mass are difficult to capture via this model as it works at a single spatial
      scale. This paper proposes a locally adaptive 3D multi-resolution Nakagami-based
      fractal feature descriptor that extends Nakagami-based texture analysis to
      accommodate subtle speckle spatial frequency tissue intensity variability in
      volumetric scans. Local textural fractal descriptors - which are invariant to
      affine intensity changes - are extracted from volumetric patches at different
      spatial resolutions from voxel lattice-based generated shape and scale Nakagami
      parameters. Using ultrasound radio-frequency datasets we found that after
      applying an adaptive fractal decomposition label transfer approach on top of the
      generated Nakagami voxels, tissue characterization results were superior to the
      state of art. Experimental results on real 3D ultrasonic pre-clinical and
      clinical datasets suggest that describing tumor intra-heterogeneity via this
      descriptor may facilitate improved prediction of therapy response and disease
      characterization. 

PMID- 25595525
TI  - Genotype-guided coumarin dosing: where are we now and where do we need to go
      next?
AB  - INTRODUCTION: A large proportion of the coumarin dose variability is explained by
      environmental factors and by common genetic variants in the VKORC1 and CYP2C9
      genes. Genotype-guided coumarin dosing has been proposed for a more accurate
      prediction of the coumarin dose in order to reduce the incidence of coumarin
      related complications. AREAS COVERED: This review discusses the current state of
      coumarin pharmacogenetics, the evidence from recent randomized controlled trials
      and economic evaluations regarding the possible clinical implementation of
      genotype-guided coumarin dosing. EXPERT OPINION: When the VKORC1 and CYP2C9
      genotypes are available before the start of coumarin therapy in individuals of
      European ancestry, a genetic-guided algorithm should be used for dose
      determination. Ethnicity-specific pharmacogenetic algorithms should be tested in
      other populations. At this moment the evidence is not sufficient to support
      genotyping before coumarin therapy initiation. Based on results from recent
      randomized controlled trials, a clinical dosing algorithm could be considered in
      the initial phase of coumarin treatment. Current economic studies indicate that
      genotype-guided dosing could be cost-effective, but the clinical implementation
      of genetic-guided coumarin therapy will depend on the cost of pharmacogenetic
      tests and the availability of novel oral anticoagulants.

PMID- 25595526
TI  - Association mapping of QTLs for sclerotinia stem rot resistance in a collection
      of soybean plant introductions using a genotyping by sequencing (GBS) approach.
AB  - BACKGROUND: Sclerotinia stem rot (SSR) is the most important soybean disease in
      Eastern Canada. The development of resistant cultivars represents the most cost
      effective means of limiting the impact of this disease. In view of ensuring
      durable resistance, it is imperative to identify germplasm harbouring different
      resistance loci and to provide breeders with closely linked molecular markers to
      facilitate breeding. With this end in view, we assessed resistance using a highly
      reproducible artificial inoculation method on a diverse collection of 101 soybean
      lines, mostly composed of plant introductions (PIs) and some of which had
      previously been reported to be resistant to sclerotinia stem rot. RESULTS:
      Overall, 50% of the lines exhibited a level of resistance equal to or better than
      the resistant checks among elite material. Of the 50 lines previously reported to
      be resistant, only 20 were in this category and a few were highly susceptible
      under these inoculation conditions. The collection of lines was genetically
      characterized using a genotyping by sequencing (GBS) protocol that we have
      optimized for soybean. A total of 8,397 single nucleotide polymorphisms (SNPs)
      were obtained and used to perform an association analysis for SSR by using a
      mixed linear model as implemented in the TASSEL software. Three genomic regions
      were found to exhibit a significant association at a stringent threshold (q =
      0.10) and all of the most highly resistant PIs shared the same alleles at these
      three QTLs. The strongest association was found on chromosome Gm03 (P-value =
      2.03 * 10(-6)). The other significantly associated markers were found on
      chromosomes Gm08 and Gm20 with P-values <10(-5). CONCLUSION: This work will
      facilitate breeding efforts for increased resistance to Sclerotinia stem rot
      through the use of these PIs.

PMID- 25595527
TI  - Effect of an invasive strategy on outcome in patients >=75 years of age with non
      ST-elevation acute coronary syndrome.
AB  - The Italian Elderly ACS study was the first randomized controlled trial comparing
      an early aggressive with an initially conservative strategy in patients with non
      ST-segment elevation acute coronary syndromes aged >=75 years, with the results
      showing no significant benefit of early aggressive therapy. The aim of this study
      was to evaluate the outcomes of trial patients, according to the treatment
      actually received during hospitalization. The trial enrolled 313 patients. The
      primary end point was the composite of death, myocardial infarction (MI),
      disabling stroke, and repeat hospital stay for cardiovascular causes or bleeding
      within 1 year. All patients in whom coronary angiography was performed during
      initial hospitalization were defined as having undergone invasive treatment (182
      patients), whereas all patients who did not undergo coronary angiography were
      classified as medically managed (conservative treatment [CT] group, 131
      patients). The primary end point occurred in 53 patients (40.5%) in the CT group
      and 45 patients (24.7%) in the invasive treatment group (hazard ratio 0.56, 95%
      confidence interval 0.37 to 0.83, p = 0.003). The invasive treatment group showed
      significantly lower rates of MI (6% vs 13% in the CT group; hazard ratio 0.43,
      95% confidence interval 0.20 to 0.92, p = 0.034) and the aggregate of death and
      MI (14.3% vs 27.5% CT group; hazard ratio 0.48, 95% confidence interval 0.29 to
      0.81, p = 0.004). In conclusion, elderly patients with non-ST-segment elevation
      acute coronary syndromes treated invasively experienced significantly better
      survival free from the composite of all-cause mortality, nonfatal MI, disabling
      stroke, and repeat hospitalization for cardiovascular causes or bleeding. 

PMID- 25595528
TI  - TRPC1 regulates fMLP-stimulated migration and chemotaxis of neutrophil
      granulocytes.
AB  - Neutrophils form the first line of defense of the innate immune system and are
      rapidly recruited by chemotactic signals to sites of inflammation. Understanding
      the mechanisms of neutrophil chemotaxis is therefore of great interest for the
      potential development of new immunoregulatory therapies. It has been shown that
      members of the transient receptor potential (TRP) family of cation channels are
      involved in both cell migration and chemotaxis. In this study, we demonstrate
      that TRPC1 channels play an important role in fMLP mediated chemotaxis and
      migration of murine neutrophils. The knock-out of TRPC1 channels leads to an
      impaired migration, transmigration and chemotaxis of the neutrophils. In
      contrast, Ca2+ influx but not store release after activation of the TRPC1(-/-)
      neutrophils with fMLP is strongly enhanced. We show that the enhanced Ca2+ influx
      in the TRPC1(-/-) neutrophils is associated with a steepened front to rear
      gradient of the intracellular Ca2+ concentration with higher levels at the cell
      rear. Taken together, this paper highlights a distinct role of TRPC1 in
      neutrophil migration and chemotaxis. We propose that TRPC1 controls the activity
      of further Ca2+ influx channels and thus regulates the maintenance of
      intracellular Ca2+ gradients which are critical for cell migration. This article
      is part of a Special Issue entitled: 13th European Symposium on Calcium.

PMID- 25595530
TI  - Annexin-A5 promotes membrane resealing in human trophoblasts.
AB  - Annexin-A5 (AnxA5) is the smallest member of the annexins, a group of soluble
      proteins that bind to membranes containing negatively-charged phospholipids,
      principally phosphatidylserine, in a Ca(2+)-dependent manner. AnxA5 presents
      unique properties of binding and self-assembling on membrane surfaces, forming
      highly ordered two-dimensional (2D) arrays. We showed previously that AnxA5 plays
      a central role in the machinery of cell membrane repair of murine perivascular
      cells, promoting the resealing of membrane damages via the formation of 2D
      protein arrays at membrane disrupted sites and preventing the extension of
      membrane ruptures. As the placenta is one of the richest source of AnxA5 in
      humans, we investigated whether AnxA5 was involved in membrane repair in this
      organ. We addressed this question at the level of human trophoblasts, either
      mononucleated cytotrophoblasts or multinucleated syncytiotrophoblasts, in
      choriocarcinoma cells and primary trophoblasts. Using established procedure of
      laser irradiation and fluorescence microscopy, we observed that both human
      cytotrophoblasts and syncytiotrophoblasts repair efficiently a MUm2-size
      disruption. Compared to wild-type cells, AnxA5-deficient trophoblasts exhibit
      severe defect of membrane repair. Through specifically binding to the disrupted
      site as early as a few seconds after membrane wounding, AnxA5 promotes membrane
      resealing of injured human trophoblasts. In addition, we observed that a large
      membrane area containing the disrupted site was released in the extracellular
      milieu. We propose mechanisms ensuring membrane resealing and subsequent lesion
      removal in human trophoblasts. This article is part of a Special Issue entitled:
      13th European Symposium on Calcium.

PMID- 25595531
TI  - Chromatographic and computational assessment of lipophilicity using sum of
      ranking differences and generalized pair-correlation.
AB  - Lipophilicity (logP) represents one of the most studied and most frequently used
      fundamental physicochemical properties. At present there are several
      possibilities for its quantitative expression and many of them stems from
      chromatographic experiments. Numerous attempts have been made to compare
      different computational methods, chromatographic methods vs. computational
      approaches, as well as chromatographic methods and direct shake-flask procedure
      without definite results or these findings are not accepted generally. In the
      present work numerous chromatographically derived lipophilicity measures in
      combination with diverse computational methods were ranked and clustered using
      the novel variable discrimination and ranking approaches based on the sum of
      ranking differences and the generalized pair correlation method. Available
      literature logP data measured on HILIC, and classical reversed-phase combining
      different classes of compounds have been compared with most frequently used
      multivariate data analysis techniques (principal component and hierarchical
      cluster analysis) as well as with the conclusions in the original sources.
      Chromatographic lipophilicity measures obtained under typical reversed-phase
      conditions outperform the majority of computationally estimated logPs.
      Oppositely, in the case of HILIC none of the many proposed chromatographic
      indices overcomes any of the computationally assessed logPs. Only two of them
      (logkmin and kmin) may be selected as recommended chromatographic lipophilicity
      measures. Both ranking approaches, sum of ranking differences and generalized
      pair correlation method, although based on different backgrounds, provides highly
      similar variable ordering and grouping leading to the same conclusions. 

PMID- 25595532
TI  - Search for improved fluorinated stationary phases for separation of fluorine
      containing pharmaceuticals from their desfluoro analogs.
AB  - Evaluation of a several fluorine-containing stationary phases for the
      chromatographic separation of fluorine-containing pharmaceuticals from their
      corresponding desfluoro analogs revealed a number of perfluoroaryl and
      perfluoroalky stationary phases that afford good separations. These fluorous
      stationary phases exhibit greater retention for the fluorine-containing compounds
      relative to the H-containing analogs, consistent with a fluorophilic retention
      mechanism. While both perfluoroalkyl and perfluoroaryl stationary phases afford
      adequate resolution, the perfluoroaryl columns generally exhibit superior
      separation factor (alpha) and peak efficiency (N), resulting in faster baseline
      separations, with the Hypersil Gold PFP and Poroshell 120 PFP columns providing
      the best overall performance for the test group studied. 

PMID- 25595529
TI  - Mitochondrial dynamics and viral infections: A close nexus.
AB  - Viruses manipulate cellular machinery and functions to subvert intracellular
      environment conducive for viral proliferation. They strategically alter functions
      of the multitasking mitochondria to influence energy production, metabolism,
      survival, and immune signaling. Mitochondria either occur as heterogeneous
      population of individual organelles or large interconnected tubular network. The
      mitochondrial network is highly susceptible to physiological and environmental
      insults, including viral infections, and is dynamically maintained by
      mitochondrial fission and fusion. Mitochondrial dynamics in tandem with
      mitochondria-selective autophagy 'mitophagy' coordinates mitochondrial quality
      control and homeostasis. Mitochondrial dynamics impacts cellular homeostasis,
      metabolism, and innate-immune signaling, and thus can be major determinant of the
      outcome of viral infections. Herein, we review how mitochondrial dynamics is
      affected during viral infections and how this complex interplay benefits the
      viral infectious process and associated diseases.

PMID- 25595533
TI  - New solvent systems for gradient counter-current chromatography in separation of
      betanin and its derivatives from processed Beta vulgaris L. juice.
AB  - Betalains, natural plant pigments, are beneficial compounds due to their
      antioxidant and possible chemoprotective properties. A mixture of betalains:
      betanin/isobetanin, decarboxybetanins and neobetanin from processed red beet
      roots (Beta vulgaris L.) juice was separated in food-grade, gradient solvent
      systems using high-performance counter-current chromatography (HPCCC). The
      decarboxylated and dehydrogenated betanins were obtained by thermal degradation
      of betanin/isobetanin from processed B. vulgaris L. juice under mild conditions.
      Two solvent systems (differing in their composition by phosphoric acid and
      ethanol volume gradient) consisting of BuOH-EtOH-NaClsolution-H2O-H3PO4
      (v/v/v/v/v, 1300:200-1000:1300:700:2.5-10) in the 'tail-to-head' mode were run.
      The flow rate of the mobile phase (organic phase) was 1.0 or 2.0 ml/min and the
      column rotation speed was 1,600 rpm (20 degrees C). The retention of the solvent
      system stationary phase (aqueous phase) was ca. 80%. The system with the acid and
      ethanol volume gradient consisting of BuOH-EtOH-NaClsolution-H2O-H3PO4
      (v/v/v/v/v, 1300:200-240:1300:700:2.5-4.5) pumped at 2.0 ml/min was the most
      effective for a separation of betanin/isobetanin, 17-decarboxy-betanin/
      isobetanin, 2-decarboxy-betanin/-isobetanin, 2,17-bidecarboxy-betanin/-isobetanin
      pairs as well as neobetanin. The pigments were detected by LC-DAD and LC-MS. The
      results are crucial in the application of completely food-grade solvent systems
      in separation of food-grade compounds as well, and the systems can possibly be
      extended to other ionizable and polar compounds with potential health benefits.
      In particular, the method is applicable for the isolation and purification of
      betalains present in such rich sources as B. vulgaris L. roots as well as cacti
      fruits and Amaranthaceae flowering plants due to modification possibilities of
      the solvent systems polarity.

PMID- 25595535
TI  - Technology transfer of brain-computer interfaces as assistive technology:
      barriers and opportunities.
AB  - This paper provides an analysis of perspectives from different stakeholders on
      the state-of-the-art of BCI. Three barriers for technology transfer of BCIs as
      access technologies are identified. First, BCIs are developed with a narrow focus
      on creating a reliable technology, while a broader focus on creating a usable
      technology is needed. Second, the potential target group, which could benefit
      from BCIs as access technologies is expected to be very small. Development costs
      are therefore high, while reimbursements are expected to be low, which challenges
      the commercial viability. Third, potential target users should be much more
      included in the design process of BCIs to ensure that the end-products meet
      technical, ethical, legal and social requirements. These three issues need to be
      urgently addressed so that target users may benefit from this promising
      technology. 

PMID- 25595534
TI  - Combined effects of potassium chloride and ethanol as mobile phase modulators on
      hydrophobic interaction and reversed-phase chromatography of three insulin
      variants.
AB  - The two main chromatographic modes based on hydrophobicity, hydrophobic
      interaction chromatography (HIC) and reversed-phase chromatography (RPC), are
      widely used for both analytical and preparative chromatography of proteins in the
      pharmaceutical industry. Despite the extensive application of these separation
      methods, and the vast amount of studies performed on HIC and RPC over the
      decades, the underlying phenomena remain elusive. As part of a systematic study
      of the influence of mobile phase modulators in hydrophobicity-based
      chromatography, we have investigated the effects of both KCl and ethanol on the
      retention of three insulin variants on two HIC adsorbents and two RPC adsorbents.
      The focus was on the linear adsorption range, separating the modulator effects
      from the capacity effects, but some complementary experiments at higher load were
      included to further investigate observed phenomena. The results show that the
      modulators have the same effect on the two RPC adsorbents in the linear range,
      indicating that the modulator concentration only affects the activity of the
      solute in the mobile phase, and not that of the solute-ligand complex, or that of
      the ligand. Unfortunately, the HIC adsorbents did not show the same behavior.
      However, the insulin variants displayed a strong tendency toward self-association
      on both HIC adsorbents; on one in particular. Since this causes peak fronting,
      the retention is affected, and this could probably explain the lack of congruity.
      This conclusion was supported by the results from the non-linear range
      experiments which were indicative of double-layer adsorption on the HIC
      adsorbents, while the RPC adsorbents gave the anticipated increased tailing at
      higher load. 

PMID- 25595536
TI  - Myeloid dendritic cells: Development, functions, and role in atherosclerotic
      inflammation.
AB  - Myeloid dendritic cells (mDCs) comprise a heterogeneous population of
      professional antigen-presenting cells, which are responsible for capture,
      processing, and presentation of antigens on their surface to T cells. mDCs serve
      as a bridge linking adaptive and innate immune responses. To date, the
      development of DC lineage in bone marrow is better characterized in mice than in
      humans. DCs and macrophages share the common myeloid progenitor called macrophage
      dendritic cell progenitor (MDP) that gives rise to monocytoid lineage and common
      DC progenitors (CDPs). CDP in turn gives rise to plasmacytoid DCs and
      predendritic cells (pre-mDCs) that are common precursor of myeloid CD11b+ and
      CD8alpha(+) DCs. The development and commitment of mDCs is regulated by several
      transcription and hematopoietic growth factors of which CCr7, Zbtb46, and Flt3
      represent 'core' genes responsible for development and functional and phenotypic
      maintenance of mDCs. mDCs were shown to be involved in the pathogenesis of many
      autoimmune and inflammatory diseases including atherosclerosis. In atherogenesis,
      different subsets of mDCs could possess both proatherogenic (e.g.
      proinflammatory) and atheroprotective (e.g. anti-inflammatory and tolerogenic)
      activities. The proinflammatory role of mDCs is consisted in production of
      inflammatory molecules and priming proinflammatory subsets of effector T cells.
      In contrast, tolerogenic mDCs fight against inflammation through arrest of
      activity of proinflammatory T cells and macrophages and induction of
      immunosuppressive regulatory T cells. Microenvironmental conditions trigger
      differentiation of mDCs to acquire proinflammatory or regulatory properties. 

PMID- 25595537
TI  - Sorption behaviour of nonylphenol and nonylphenol monoethoxylate in soils.
AB  - Sorption behaviour of two alkylphenolic compounds (APCs), nonylphenol (NP) and
      nonylphenol monoethoxylate (NP1EO), was studied in five soils with contrasting
      characteristics. Sorption isotherms were obtained by equilibrating the soil
      samples with 0.01 mol L(-1) CaCl2 solutions containing different initial
      concentrations of NP or NP1EO. Linear fitting was generally appropriate for
      describing the sorption behaviour of NP and NP1EO in the soils, with the
      exception of two cases, for which the Freundlich model was more suitable for
      describing the sorption pattern of NP1EO. Solid-liquid distribution coefficients
      derived from sorption isotherms (Kd) varied from 24 to 1059 mL g(-1) for NP and
      from 51 to 740 mL g(-1) for NP1EO. For most soils, sorption Kd values were higher
      for NP than for NP1EO due to the higher hydrophobicity of NP. Sorption
      reversibility of NP and NP1EO was also tested from desorption isotherms.
      Desorption solid-liquid distribution coefficients (Kd,des), obtained from linear
      fitting, were between 130 and 1467 mL g(-1) for NP and between 24 and 1285 mL g(
      1) for NP1EO. Kd,des values were higher than Kd values, which demonstrated that
      target compounds were irreversibly sorbed into soils, with the exception of the
      high desorption yield (45%) of NP1EO in the soil with the lowest content of
      organic matter. The fraction of soil organic carbon (FOC) was a key parameter
      that influenced the sorption of NP and NP1EO in soils, with logKOC values of 4.0
      and 3.8, respectively.

PMID- 25595538
TI  - Preliminary proteomic analysis on the alterations in follicular fluid proteins
      from women undergoing natural cycles or controlled ovarian hyperstimulation.
AB  - PURPOSE: To study the differences in protein expression profiles of follicular
      fluid (FF) between controlled ovarian hyperstimulation (COH) and natural
      ovulatory cycles. METHODS: Twelve infertile women undergoing in vitro
      fertilization and embryo transfer (IVF-ET), with matched clinical information,
      were retrospectively recruited in the IVF center of our university hospital,
      including six undergoing COH and another six with natural cycles. FF was sampled
      from dominant follicles with mature oocytes. Protein expression profiles in each
      FF sample were analyzed respectively using two-dimensional gel electrophoresis.
      Differentially expressed proteins were identified using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and
      validated by western blotting. Differentially expressed proteins were further
      analyzed using Ingenuity Pathway Analysis (IPA) software. RESULTS: Two proteins
      were downregulated and 11 proteins were upregulated (change >=1.5-fold, P < 0.05)
      in the COH group. We identified one down-egulated and seven upregulated proteins
      using MALDI-TOF MS. Four differentially expressed proteins, including
      transferrin, complement component C3 (C3), haptoglobin and alpha-1-antitrypsin
      (AAT), were further validated by rate nephelometry and western blotting analyses.
      The IPA analysis revealed a significant network involved in the humoral immune
      and inflammatory responses. CONCLUSIONS: The eight differentially expressed
      proteins were related to immune and inflammatory responses in the ovary. Our
      results provide new insights into the influence of COH on follicular (spp)
      development and IVF outcomes.

PMID- 25595539
TI  - Poor-responder patients do not benefit from intracytoplasmic morphologically
      selected sperm injection.
AB  - PURPOSE: To compare the outcomes of ICSI and IMSI in women presenting with poor
      ovarian response. METHODS: Data of IMSI cycles performed from January 2011 to
      December 2013 were included in this retrospective cohort study. Patients were
      divided into two groups: normoresponder patients (NR group; patients with > 4
      oocytes retrieved) and poor-responder patients (PR group; patients with <= 4
      oocytes retrieved). Patients who underwent IMSI were matched with patients who
      underwent ICSI in the same period. The ICSI and IMSI outcomes were compared in
      the NR and PR groups. RESULTS: A total of 414 matched cycles were included in
      this study. The NR group comprised 324 cycles (164 ICSI and 160 IMSI cycles), and
      the PR group comprised 90 cycles (43 ICSI and 47 IMSI cycles). In the NR group,
      no significant differences were observed between the ICSI- and IMSI-treated
      couples regarding cycle outcomes. In the PR group, fertilisation rate was
      significantly lower in IMSI-treated couples (53.9% +/- 36.7% vs. 79.8% +/-
      29.3%). The proportion of cycles with embryo transfer (57.4 vs. 79.1%) and the
      number of transferred embryos (1.5 +/- 0.8 vs. 1.9 +/- 0.7) were significantly
      lower in IMSI compared with ICSI. Implantation, pregnancy and miscarriage rates
      were similar when ICSI or IMSI were performed. CONCLUSIONS: Our results suggest
      that unselected couples undergoing ICSI that present with poor ovarian response
      to controlled ovarian stimulation do not benefit from sperm selection under high
      magnification prior to ICSI.

PMID- 25595540
TI  - Ovarian stimulation and in-vitro fertilization outcomes of cancer patients
      undergoing fertility preservation compared to age matched controls: a 17-year
      experience.
AB  - PURPOSE: To compare the in-vitro fertilization (IVF) outcomes of cancer patients
      who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to
      gonadotoxic therapy to those of age and time-matched controls with tubal factor
      infertility. METHODS: All cancer patients who underwent embryo/oocyte
      cryopreservation at our institution from 1997 to 2014 were reviewed. Primary
      outcomes were total dose of gonadotropins used, number of oocytes retrieved, and
      number of 2pn embryos obtained. Outcomes were compared to age-matched controls
      with tubal-factor infertility who underwent a fresh embryo transfer within the
      same relative time period as the IVF cycle of the cancer patient. RESULTS: Sixty
      three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo
      transfer. One hundred twenty-two age-matched controls underwent IVF cycles with
      fresh transfer, and 23 returned for frozen embryo transfer. No difference was
      seen between cancer patients and controls with respect to total ampules of
      gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes
      retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos
      obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per
      transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p
      = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively
      (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in
      twins (44 vs. 14 %; p = 0.035). CONCLUSIONS: Most IVF outcomes appear comparable
      for cancer patients and age-matched controls. Higher twin pregnancy rates in
      cancer patients may reflect lack of underlying infertility or need for cancer
      specific transfer guidelines.

PMID- 25595541
TI  - Hypersensitivity to laminaria: a case report and review of literature.
AB  - We report a case of laminaria hypersensitivity treated with diphenhydramine and
      corticosteroids. A literature review identified 10 previously reported cases,
      with 8 recognized as anaphylaxis, and good outcomes with corticosteroids and
      antihistamines despite limited epinephrine utilization. Laminaria
      hypersensitivity is likely IgE mediated with an increased anaphylaxis risk with
      prior exposure. 

PMID- 25595542
TI  - Near-field discrimination of sound source distance in the rabbit.
AB  - The acoustical cues and physiological processing mechanisms underlying the
      perception of the distance of sound sources are not well understood. To
      understand the relation between physiology and behavior, a first step is to use
      an animal model to study distance sensitivity. The goal of these experiments was
      to establish the capacity of the Dutch-belted rabbit to discriminate between
      sound sources at two distances. Trains of noise bursts were presented from
      speakers that were located either directly in front of the rabbit or at a 45 
      degrees  angle in azimuth. The reference speaker was positioned at distances of
      20, 40, and 60 cm from the subject, and the more distant test speaker was
      systematically moved to determine the smallest difference in distance that could
      be reliably discriminated by the subject. Noise stimuli had one of three
      bandwidths: wideband (0.1-10 kHz), low-pass (0.1-3 kHz), or high-pass (3-10 kHz).
      The mean stimulus level was 60 dB sound pressure level (SPL) at the location of
      the rabbit's head, and the level was roved over a 12-dB range from trial to trial
      to reduce the availability of level cues. An operant one-interval two-alternative
      non-forced choice task was used, with a blocked two-down-one-up tracking
      procedure to determine the distance discriminability. Rabbits were consistently
      able to discriminate two distances when they were sufficiently separated.
      Sensitivity was better when the reference distance was 60 cm at either azimuth
      (distance ratio = 1.5) and was worse when the reference distance was 20 cm
      (distance ratio = 2.4 at 0  degrees  and 1.75 at 45  degrees ).

PMID- 25595543
TI  - A life-saving therapy in Class I HELLP syndrome: Therapeutic plasma exchange.
AB  - HELLP syndrome, which can affect multiple organ systems and cause maternal and
      fetal mortality, is a serious complication of pregnancy characterized by
      microangiopathic hemolytic anemia, elevation of liver enzymes, and
      thrombocytopenia. Delivering the infant usually suffices for the treatment of
      this syndrome. In cases with Class I HELLP syndrome, however, the clinical
      picture may rapidly deteriorate despite delivery. In this paper we presented the
      outcomes with the use of therapeutic plasma exchange in cases with class I HELLP
      syndrome. This study included 21 patients diagnosed with the Class I HELLP
      syndrome at Inonu University Faculty of Medicine, Department of Hematology
      between 2011 and 2014. A central venous catheter was placed and plasma exchange
      therapy was begun in patients unresponsive to delivery, steroid, and supportive
      therapy (blood and blood products, antihypertensive therapy, intravenous fluid
      administration, and antibiotics) within 24 hours after the diagnosis of Class I
      HELLP syndrome according to the Mississippi Criteria. All patients underwent
      therapeutic plasma exchange for three sessions each with a 1:1 volume. Hemogram
      and biochemical parameters of the patients were evaluated before and after the
      procedure. According to results, there was a statistically significant decrease
      in total bilirubin, LDH, AST, and ALT levels whereas a significant increase in
      platelet count was observed. Hemoglobin levels were increased, although this
      increase was not statistically significant. HELLP syndrome is primarily treated
      with the delivery of infant; however, some cases may show disease progression
      despite completion of delivery. As a potential cause of both maternal and fetal
      mortality, HELLP syndrome condition should be aggressively treated. Therapeutic
      plasma exchange is one of the available treatment options. Our study has found
      that postpartum use of plasma exchange therapy within 24 hours is an efficient
      and lifesaving treatment choice in Class I HELLP syndrome. 

PMID- 25595544
TI  - Highlights of the role of PMP in health & disease & advancements in PRT and
      quality in transfusion establishments.

PMID- 25595546
TI  - Small subunit of a cold-resistant plant, Timothy, does not significantly alter
      the catalytic properties of Rubisco in transgenic rice.
AB  - Effects of overexpression of high activity-type Rubisco small subunit (RbcS) from
      a cold-resistant plant, timothy (Phleum pratense), on kinetic properties of
      Rubisco were studied in rice (Oryza sativa). The full-length mRNA sequence of
      timothy RbcS (PpRbcS1) was determined by 5'RACE and 3'RACE. The coding sequence
      of PpRbcS1 was fused to the chlorophyll a/b-binding protein promoter and
      introduced into rice. PpRbcS was highly expressed in leaf blade and accounted for
      approximately 30 % of total RbcS in homozygous transgenic lines. However, the
      catalytic turnover rate and K m for CO2 of Rubisco did not significantly change
      in these transgenic lines compared to non-transgenic rice, suggesting that
      PpRbcS1 is not effective for improvement of catalytic efficiency of rice Rubisco.
      The photosynthetic rate and growth were essentially unchanged, whereas the
      photosynthetic rate at low CO2 condition was marginally increased in transgenic
      lines. Rubisco content was significantly increased, whereas soluble protein,
      nitrogen, and chlorophyll contents were unchanged in transgenic lines compared to
      non-transgenic rice. Because the kinetic properties were similar, observed slight
      increase in photosynthetic rate at low CO2 is considered to be large due to
      increase in Rubisco content in transgenic lines. Introduction of foreign RbcS is
      an effective approach for the improvement of Rubisco kinetics and photosynthesis.
      However, in this study, it was suggested that RbcS of high activity-type Rubisco,
      even showing higher amino acid identity with rice RbcS, did not always enhance
      the catalytic turnover rate of Rubisco in rice. Thus, we should carefully select
      RbcS to be overexpressed before introduction.

PMID- 25595545
TI  - Genetic and genomic analysis of RNases in model cyanobacteria.
AB  - Cyanobacteria are diverse photosynthetic microbes with the ability to convert CO2
      into useful products. However, metabolic engineering of cyanobacteria remains
      challenging because of the limited resources for modifying the expression of
      endogenous and exogenous biochemical pathways. Fine-tuned control of protein
      production will be critical to optimize the biological conversion of CO2 into
      desirable molecules. Messenger RNAs (mRNAs) are labile intermediates that play
      critical roles in determining the translation rate and steady-state protein
      concentrations in the cell. The majority of studies on mRNA turnover have focused
      on the model heterotrophic bacteria Escherichia coli and Bacillus subtilis. These
      studies have elucidated many RNA modifying and processing enzymes and have
      highlighted the differences between these Gram-negative and Gram-positive
      bacteria, respectively. In contrast, much less is known about mRNA turnover in
      cyanobacteria. We generated a compendium of the major ribonucleases (RNases) and
      provide an in-depth analysis of RNase III-like enzymes in commonly studied and
      diverse cyanobacteria. Furthermore, using targeted gene deletion, we genetically
      dissected the RNases in Synechococcus sp. PCC 7002, one of the fastest growing
      and industrially attractive cyanobacterial strains. We found that all three
      cyanobacterial homologs of RNase III and a member of the RNase II/R family are
      not essential under standard laboratory conditions, while homologs of RNase E/G,
      RNase J1/J2, PNPase, and a different member of the RNase II/R family appear to be
      essential for growth. This work will enhance our understanding of native control
      of gene expression and will facilitate the development of an RNA-based toolkit
      for metabolic engineering in cyanobacteria. 

PMID- 25595547
TI  - Craniometric analysis for estimation of stature in Nepalese population--A study
      on an autopsy sample.
AB  - Establishing the identity of the deceased becomes essential when highly
      decomposed bodies, mutilated body parts or skeletal remains are recovered from
      mass fatality sites. In these situations, estimation of stature along with other
      parameters such as age, sex and race/ethnicity becomes important to establish the
      biological profile of the deceased. Following the Maoist insurgency in Nepal,
      there have been numerous discoveries of unidentified human remains in mass graves
      or otherwise. No systemic studies and anthropological data on the Nepalese
      population however, is available posing problems in anthropologic evaluation of
      the remains. The sample of the present study consisted of 200 autopsied cases
      (148 males and 52 female adult cadavers). During the autopsy, the scalp was
      reflected after giving a coronal incision extending from one mastoid to the other
      exposing the cranium in each case. Maximum cranial length (MCL), maximum cranial
      breadth (MCB), bi-zygomatic breadth (BZB), minimum frontal breadth (MFB) and
      length of parietal chord (PC) were then measured. Stature was measured as the
      length of the body from head to heel in centimeters with the heel, buttocks, back
      of the shoulders and the head in contact with the autopsy table. Linear and
      stepwise multiple regression models were derived for estimation of stature from
      cranial measurements. Univariate, bivariate and multivariate regression models
      show statistically significant correlation between stature and the cranial
      measurements. The present study opines that the stature estimation from cranial
      dimensions using multivariate linear regression models is more accurate than
      those of the univariate and bivariate regression models. This study presents a
      rare data from Nepalese population that show typical Asian features and thus, is
      significant from anthropologic and genetic point of view. The study observations
      further contribute a baseline data bank for forensic pathologists and
      specialists. 

PMID- 25595548
TI  - Testing the applicability of six macroscopic skeletal aging techniques on a
      modern Southeast Asian sample.
AB  - Most macroscopic skeletal aging techniques used by forensic anthropologists have
      been developed and tested only on reference material from western populations.
      This study examined the performance of six aging techniques on a known age sample
      of 88 Southeast Asian individuals. Methods examined included the Suchey-Brooks
      method of aging the symphyseal face of the os pubis (Brooks and Suchey, Hum.
      Evol. 5 (1990) 227), Buckberry and Chamberlain's, Am. J. Phys. Anthropol. 119
      (2002) 231 and Osborne et al.'s, J. Forensic Sci. 49 (2004) 1 revisions of the
      Lovejoy et al., Am. J. Phys. Anthropol. 68 (1985) 15 method of aging the
      auricular surface of the ilium, Iscan et al.'s, J. Forensic Sci. 29 (1984) 1094,
      Iscan et al.'s, J. Forensic Sci. 30 (1985) 853 method of aging the sternal end of
      the fourth rib, and Meindl and Lovejoy's, Am. J. Phys. Anthropol. 68 (1985) 57
      methods for aging both lateral-anterior and vault sutures on the cranium. The
      results of this study indicate that application of aging techniques commonly used
      in forensic anthropology to individuals identified as Asian, and more
      specifically Southeast Asian, should not be undertaken injudiciously. Of the six
      individual methods tested here, the Suchey-Brooks pubic symphysis aging method
      performs best, though average age estimates were still off by nearly 10 years or
      greater. Methods for aging the auricular surface perform next best, though the
      Osborne et al. method works better for individuals below 50 years and the
      Buckberry and Chamberlain method works better for those above 50 years. Methods
      for age estimation from the sternal ends of the fourth rib and vault and lateral
      anterior cranial sutures perform poorly and are not recommended for use on
      remains of Southeast Asian ancestry. Combining age estimates from multiple
      indicators, specifically the pubic symphysis and one auricular surface method,
      was superior to individual methods. Data and a worked example are provided for
      calculating the conditional probability that an individual belongs to a
      particular age decade, though overall age estimates may still be broad. 

PMID- 25595549
TI  - Maximal cardiac output in athletes: influence of age.
AB  - BACKGROUND: The decline in maximal oxygen consumption (VO2max) with age seems to
      be exacerbated in endurance-trained athletes (EA) relative to untrained healthy
      subjects. Whether maximal cardiac output (Qmax) parallels this group-specific
      decline with age remains uncertain. Therefore, we sought to systematically review
      the literature and determine whether Qmax is similarly enhanced in EA across all
      ages relative to age-matched untrained counterparts. DESIGN AND METHODS: We
      conducted a systematic search of MEDLINE, Cochrane and Web of Science from their
      inceptions until June 2014 for articles evaluating Qmax in athletes. A meta
      analysis was performed to determine the standardized mean difference (SMD) in
      Qmax between EA and age-matched untrained healthy subjects. Included studies had
      to (i) comprise EA and control groups matched for body size or (ii) present Qmax
      values normalized for body size. Subgroup and meta-regression analyses were used
      to study the influence of age and potential moderating factors. RESULTS: Eighteen
      studies were selected after systematic review, comprising 268 EA and 232 age
      matched untrained subjects. Nine studies involved young EA (mean age <=40 years)
      while nine studies involved master EA (mean age >55 years). After data pooling,
      young and master EA groups showed higher Qmax compared with control groups (SMD =
      1.49 and SMD = 1.68, respectively; both p < 0.0001). The SMD in Qmax between EA
      and control groups was similar in studies in young EA compared with studies in
      master EA (p = 0.61). Moreover, the SMD in VO2max between EA and control groups
      did not differ in studies in young EA compared with studies in master EA (p =
      0.37). In meta-regression analyses, the difference in percentage of body fat
      between EA and control groups was inversely associated with the SMD in Qmax (B = 
      0.17, p = 0.01) and the SMD in VO2max (B = -0.20, p = 0.01). Mean age was not
      associated with the SMD in Qmax (B = -0.001, P = 0.90) nor with the SMD in VO2max
      (B = 0.01, P = 0.58). CONCLUSIONS: Based on current published studies, the
      enhanced Qmax observed in EA compared with untrained healthy subjects matched for
      body size is not affected by age but may be related, at least in part, to the
      improved body composition of EA.

PMID- 25595550
TI  - Treat-to-target versus dose-adapted statin treatment of cholesterol to reduce
      cardiovascular risk.
AB  - Clinical guidelines should be based on the best available evidence and are of
      great importance for patient care and disease prevention. In this respect, the
      2013 American College of Cardiology/American Heart Association report is highly
      appreciated and well-recognized. The report included critical questions
      concerning hypercholesterolaemia, but its translation into a clinical guideline
      initiated intense debate worldwide because of the recommendation to switch from a
      treat-to-target approach for low-density-lipoprotein-cholesterol to a statin dose
      based strategy. 

PMID- 25595551
TI  - Cause-specific mortality and years of life lost in patients with different
      manifestations of vascular disease.
AB  - BACKGROUND: Patients with cardiovascular disease might be at increased risk of
      non-vascular mortality due to shared risk factors. Our aim was to evaluate causes
      of death and years of life lost (YLL) in patients with different manifestations
      of vascular disease. DESIGN: The design was a prospective cohort study. METHODS:
      A total of 5911 patients with stable coronary artery disease, cerebrovascular
      disease, peripheral artery disease (PAD), abdominal aortic aneurysm or
      polyvascular disease were followed-up for mortality. Cause-specific standardised
      mortality ratios (SMRs) and YLL, compared to the Dutch population, were
      estimated. Determinants for cause-specific mortality were evaluated using
      competing risks models. RESULTS: During a median follow-up of 6.0 years
      (interquartile range (IQR): 3.1-9.2), 958 (16.2%) patients died. All-cause
      mortality was increased compared to the general population (SMR: 1.26, 95%
      confidence interval (CI): 1.18-1.34). Patients with PAD and polyvascular disease
      were at highest risk, especially for ischaemic heart disease (SMR: 2.52, 95% CI:
      1.70-3.60 and SMR: 3.97, 95% CI: 3.18-4.90, respectively). Patients with PAD were
      at increased risk of dying from cancer (SMR: 1.67, 95% CI: 1.25-2.17). On
      average, patients with vascular disease of >=50 years died 7.8 years younger than
      the general population, with 80% of the excess YLL attributable to cardiovascular
      disease. In middle-aged patients the excess YLL were about 10 years, of which 24%
      were lost due to cancer. Important determinants for mortality were male gender,
      smoking, physical inactivity, renal insufficiency and polyvascular disease.
      CONCLUSIONS: Patients with manifest vascular disease are at increased risk of
      both cardiovascular and cancer mortality, particularly patients with PAD or
      polyvascular disease. On average, patients with vascular disease of >=50 years
      die 7.8 years younger than the general population.

PMID- 25595552
TI  - The "comma sign": an anatomical investigation (dissection of the rotator interval
      in 14 cadaveric shoulders).
AB  - PURPOSE: The aim of the present study was to describe the precise anatomy of the
      so-called "Comma Sign" which has been observed during arthroscopy in retracted
      subscapularis (SSC) tears. METHODS: Fourteen fresh cadaveric shoulders were
      prepared to obtain an articular view comparable to arthroscopic posterior portal
      view. A step-by-step dissection was carried out to verify the presence of any
      anatomic structure inserting directly on the lateral margin of the SSC tendon. A
      sequential detachment of the superior gleno-humeral ligament (SGHL), the coraco
      humeral ligament (CHL), and the SSC tendon from their bony humeral insertions was
      performed. Under intra-articular and extra-articular view, the SSC and its
      connections with the supraspinatus (SS), the SGHL and the CHL were evaluated.
      RESULTS: The detachment of the CHL and the SGHL from the humerus did not reveal
      any structure directly inserted on the superior-lateral margin of the SSC tendon.
      However, when the SSC tendon was excised from the lesser tuberosity and pulled
      medially, a bundle of fibers, which inserted directly onto its superior-lateral
      edge, was constantly observed. CONCLUSIONS: We constantly found an effective link
      between the superior-lateral corner of the SSC tendon and a bundle of fibers
      coming from SS and CHL. It became visible only after medial traction of the
      detached SSC. This structure yields the "Comma Sign" in subscapularis tendon
      tears.

PMID- 25595553
TI  - A generalized Watterson estimator for next-generation sequencing: From trios to
      autopolyploids.
AB  - Several variations of the Watterson estimator of variability for Next Generation
      Sequencing (NGS) data have been proposed in the literature. We present a unified
      framework for generalized Watterson estimators based on Maximum Composite
      Likelihood, which encompasses most of the existing estimators. We propose this
      class of unbiased estimators as generalized Watterson estimators for a large
      class of NGS data, including pools and trios. We also discuss the relation with
      the estimators proposed in the literature and show that they admit two equivalent
      but seemingly different forms, deriving a set of combinatorial identities as a
      byproduct. Finally, we give a detailed treatment of Watterson estimators for
      single or multiple autopolyploid individuals.

PMID- 25595555
TI  - Are RNAi and miRNA therapeutics truly dead?
AB  - Only a few years ago pharmaceutical companies were excited about the potential of
      RNA interference (RNAi). Now, financial volatility and subsequent dissolutions of
      in-house facilities by pharmaceutical companies have had media channels
      pronouncing that RNAi therapeutics are dead. However, advances in nanomedicine
      may now help the vast potential of RNAi therapeutics to be fulfilled. 

PMID- 25595556
TI  - Engineering therapeutic proteins for cell entry: the natural approach.
AB  - Owing to the challenges of cell entry, protein-based therapies have so far been
      restricted to extracellular targets, whereas intracellular targets have been
      almost exclusively addressed by small molecules. The specificity and potency of
      proteins would enable them to be effective intracellular drugs, provided that the
      proteins are delivered efficiently to appropriate intracellular compartments
      within specific cell types. By mimicking the natural mechanisms of toxins and
      other natural proteins, new intracellular delivery systems are being developed,
      the first of which are showing clinical efficacy. This review highlights a range
      of ingenious approaches designed to adapt natural entry mechanisms to facilitate
      delivery of proteins and open up a range of validated intracellular targets to
      modulation by potent and specific therapeutic drugs. 

PMID- 25595554
TI  - Methods to determine intestinal permeability and bacterial translocation during
      liver disease.
AB  - Liver disease is often times associated with increased intestinal permeability. A
      disruption of the gut barrier allows microbial products and viable bacteria to
      translocate from the intestinal lumen to extraintestinal organs. The majority of
      the venous blood from the intestinal tract is drained into the portal
      circulation, which is part of the dual hepatic blood supply. The liver is
      therefore the first organ in the body to encounter not only absorbed nutrients,
      but also gut-derived bacteria and pathogen associated molecular patterns (PAMPs).
      Chronic exposure to increased levels of PAMPs has been linked to disease
      progression during early stages and to infectious complications during late
      stages of liver disease (cirrhosis). It is therefore important to assess and
      monitor gut barrier dysfunction during hepatic disease. We review methods to
      assess intestinal barrier disruption and discuss advantages and disadvantages. We
      will in particular focus on methods that we have used to measure increased
      intestinal permeability and bacterial translocation in experimental liver disease
      models. 

PMID- 25595557
TI  - Quantifying on- and off-target genome editing.
AB  - Genome editing with engineered nucleases is a rapidly growing field thanks to
      transformative technologies that allow researchers to precisely alter genomes for
      numerous applications including basic research, biotechnology, and human gene
      therapy. While the ability to make precise and controlled changes at specified
      sites throughout the genome has grown tremendously in recent years, we still lack
      a comprehensive and standardized battery of assays for measuring the different
      genome editing outcomes created at endogenous genomic loci. Here we review the
      existing assays for quantifying on- and off-target genome editing and describe
      their utility in advancing the technology. We also highlight unmet assay needs
      for quantifying on- and off-target genome editing outcomes and discuss their
      importance for the genome editing field. 

PMID- 25595558
TI  - Sp1 regulates Raf/MEK/ERK-induced p21(CIP1) transcription in TP53-mutated cancer
      cells.
AB  - We previously reported that the upregulation of mortalin, an Hsp70 family
      chaperone, is important for B-Raf(V600E) tumor cells to bypass p21(CIP1)
      expression, which is activated as a tumor-suppressive mechanism in response to
      aberrant MEK/ERK activation (Wu et al., 2013). Interestingly, mortalin depletion
      induced p21(CIP1) transcription not only in wild-type TP53 but also in TP53
      mutated B-Raf(V600E) cancer cells, suggesting the presence of an additional
      mechanism for p21(CIP1) regulation. In the present study, using luciferase
      reporter truncation analysis in a TP53-mutated B-Raf(V600E) cancer cell line, SK
      MEL28, we identified a proximal p21(CIP1) promoter region responsive to mortalin
      depletion. Interestingly, when Sp1-like cis-elements in this promoter region were
      mutagenized, the p21(CIP1) promoter luciferase reporter was no longer responsive
      to mortalin depletion. Consistent with this, our ChIP analysis revealed that
      mortalin knockdown could induce Sp1 binding to p21(CIP1) promoter in a MEK/ERK
      dependent manner. Moreover, RNA interference of Sp1 substantially attenuated
      p21(CIP1) expression induced by mortalin depletion in SK-MEL28 cells. Consistent
      with this observation in SK-MEL28 cells, Sp1 was necessary for the tamoxifen
      regulated ?Raf-1:ER to induce p21(CIP1) transcription in U251 cells, in which
      TP53 is mutated. However, in contrast, Sp1 was not necessary for ?Raf-1:ER to
      induce p21(CIP1) transcription in LNCaP cells, in which TP53 is wild type. These
      data suggest that Sp1 may address TP53-independent p21(CIP1) transcription in
      Raf/MEK/ERK-activated cancer cells and that its requirement in Raf/MEK/ERK
      induced p21(CIP1) transcription is subject to TP53 status. 

PMID- 25595559
TI  - Dissipative energy loss within the left ventricle detected by vector flow mapping
      in children: Normal values and effects of age and heart rate.
AB  - BACKGROUND: Vector flow mapping (VFM) is a novel echocardiographic technology
      which enables visualization of the intraventricular flow velocity vector.
      Dissipative energy loss (EL) derived from the velocity vector field of
      intraventricular blood flow is considered to reflect the efficiency of blood
      flow, and could be an indicator of left ventricular function. We aimed to
      determine the reference values of the EL derived from VFM within the left
      ventricle. METHODS: VFM analysis was performed using echocardiography in 64
      healthy children. The velocity vector fields of the intra-left ventricular blood
      flow were obtained from the apical 5-chamber view, and the EL values during
      systole and diastole were calculated. The measurements were averaged over three
      cardiac cycles, and indexed to body surface area (BSA). RESULTS: The mean subject
      age was 6.8+/-4.3 years. The mean EL was 4.10+/-2.35mW/m/m(2) BSA during systole
      and 16.24+/-11.63mW/m/m(2) BSA during diastole. On multivariate analysis, age and
      heart rate (HR) were independent predictors of systolic EL, whereas age, HR, and
      E wave peak velocity were independent predictors of diastolic EL. The regression
      equations used to predict the BSA-indexed systolic and diastolic EL were as
      follows: log10 (systolic EL)=-0.0332-0.00213*age (months)+0.00789*HR (beats/min)
      (adjusted R(2), 0.833; p<0.0001); and log10 (diastolic EL)=0.277-0.00346*age
      (months)+0.00570*HR (beats/min)+0.00564*E wave peak velocity (cm/s) (adjusted
      R(2), 0.867; p<0.0001). CONCLUSIONS: The systolic and diastolic EL were
      positively correlated with HR and negatively correlated with age. Moreover, the
      diastolic EL was positively correlated with the E wave peak velocity. The present
      study provides reference values for the systolic and diastolic EL that can be
      used in future studies examining patients with heart disease.

PMID- 25595561
TI  - Importance of guideline adherence for unstable angina pectoris and prevention of
      serious cardiovascular events by conforming to guidelines.

PMID- 25595560
TI  - Time to and risk of cardiac events after myocardial perfusion scintigraphy.
AB  - BACKGROUND: The burden of cardiovascular disease is increasing, yet it remains
      difficult to focus preventive strategies on populations at highest absolute and
      relative risks. We compared absolute and relative cardiovascular event counts,
      plus time to first event, among patients undergoing myocardial perfusion
      scintigraphy (MPS). METHODS AND RESULTS: Our database was queried to identify
      subjects without myocardial necrosis or recent revascularization, focusing on
      cardiac death (CD) or myocardial infarction (MI). A total of 13,254 patients were
      included, 5436 (41%) without, and 7818 (59%) with ischemia. After 32+/-21 months,
      subjects without ischemia, compared to those with ischemia, had lower absolute
      (16 vs 75 events, 18% vs 82%, p<0.001) and relative (0.3% vs 1.3%, p<0.001) risk
      of CD. Similar findings were obtained for MI (52 vs 81 events, 39% vs 61%,
      p<0.001, with corresponding rates of 1.0% vs 1.4%, p<0.001, respectively).
      Medical therapy appeared associated with fewer outcomes in those without
      ischemia, with the opposite occurring for subjects with ischemia (p<0.001).
      Median times to event ranged between 13 and 25 months in patients without
      ischemia vs 2 and 14 months in those with ischemia (p<0.001 for all comparisons).
      Multivariable-adjusted and propensity matched analyses confirmed the independent
      prognostic role of myocardial ischemia and, apparently, revascularization.
      CONCLUSION: Most fatal and non-fatal cardiac events appear to occur in patients
      with evidence of myocardial ischemia at MPS, especially those with moderate or
      severe ischemia not receiving revascularization during follow-up.

PMID- 25595562
TI  - Diagnostic utility of quantitative EEG in un-medicated schizophrenia.
AB  - The aim of the current study was to evaluate the quantitative
      electroencephalography (QEEG) characteristics of patients with un-medicated
      schizophrenia (SPR) and to investigate the diagnostic utility of QEEG in
      assessing such patients during resting conditions. The subjects included 90
      patients with schizophrenia and 90 normal controls. Spectral analysis was
      performed on the absolute power of all of the electrodes across five frequency
      bands following artifact removal. We conducted a repeated-measures ANOVA to
      examine group differences within the five frequency bands across several brain
      regions and receiver operator characteristic (ROC) analyses to examine the
      discrimination ability of each frequency band. Compared with controls, patients
      with schizophrenia showed increased delta and theta activity and decreased alpha
      2 activity, particularly in the frontocentral area. There were no significant
      differences in the alpha 1 and beta activity. The ROC analysis performed on the
      delta frequency band generated the best result, with an overall classification
      accuracy of 62.2%. The results of this study confirmed the characteristics of the
      QEEG power in un-medicated schizophrenia patients compared with normal controls.
      These findings suggest that a resting EEG test can be a supportive tool for
      evaluating patients with schizophrenia. 

PMID- 25595563
TI  - Prevalence and associated factors for temporomandibular disorders in Chinese
      civilian pilots.
AB  - PURPOSE: Piloting is a special profession with prolonged stress, which could
      induce the occurrence of TMD. This sample is useful to reduce the effect of
      confounders in the analyses. Based on this, the present study aims to determine
      the prevalence and associated factors for TMD in civilian pilots of China.
      METHODS: A cross-sectional epidemiological survey was carried out in 616 male
      subjects (aged 23-52 years). The questionnaire included general information,
      chewing preference (bilateral or unilateral), and Trait Anxiety section of
      Spielberger State-Trait Anxiety Inventory (STAI-T). The clinical examination
      contained TMD screening per research diagnostic criteria for TMD and diagnosis of
      sleep bruxism per American Academy of Sleep Medicine standards. The level of
      statistical significance was set at P <= 0.05. RESULTS: The program was conducted
      from June 2012 to April 2013, in which period, and the percentage of TMD in the
      samples we examined was 33.3 % (=205/616). Only high anxiety (OR 2.48; 95 % CI
      1.25-4.90) and unilateral chewing preference (OR 12.67; 95 % CI 7.77-20.65) were
      the most significant associated factors with TMD. Also, salivary cortisol and the
      STAI-T score had a significant correlation (r = 0.47, P < 0.001). CONCLUSIONS: It
      was more reliable to study the associated factors on TMD with the exclusion of
      the possible confounding factors, and only unilateral chewing preference and
      psychological stress had a significant association with TMD. In addition, the
      salivary cortisol levels might assist to assess psychological stress in
      epidemiological research.

PMID- 25595564
TI  - Inhibition of matrix metalloproteinase activity in human dentin via novel
      antibacterial monomer.
AB  - OBJECTIVE: Dentin-composite bond failure is caused by factors including hybrid
      layer degradation, which in turn can be caused by hydrolysis and enzymatic
      degradation of the exposed collagen in the dentin. The objectives of this study
      were to investigate a new antibacterial monomer (dimethylaminododecyl
      methacrylate, DMADDM) as an inhibitor for matrix metalloproteinases (MMPs), and
      to determine the effects of DMADDM on both soluble recombinant human MMPs
      (rhMMPs) and dentin matrix-bound endogenous MMPs. METHODS: Inhibitory effects of
      DMADDM at six mass% (0.1% to 10%) on soluble rhMMP-8 and rhMMP-9 were measured
      using a colorimetic assay. Matrix-bound endogenous MMP activity was evaluated in
      demineralized human dentin. Dentin beams were divided into four groups (n=10) and
      incubated in calcium- and zinc-containing media (control medium); or control
      medium+0.2% chlorhexidine (CHX); 5% 12-methacryloyloxydodecylpyridinium bromide
      (MDPB); or 5% DMADDM. Dissolution of dentin collagen peptides was evaluated by
      mechanical testing in three-point flexure, loss of dentin mass, and a
      hydroxyproline assay. RESULTS: Use of 0.1% to 10% DMADDM exhibited a strong
      concentration-dependent anti-MMP effect, reaching 90% of inhibition on rhMMP-8
      and rhMMP-9 at 5% DMADDM concentration. Dentin beams in medium with 5% DMADDM
      showed 34% decrease in elastic modulus (vs. 73% decrease for control), 3% loss of
      dry dentin mass (vs. 28% loss for control), and significantly less solubilized
      hydroxyproline when compared with control (p<0.05). SIGNIFICANCE: The new
      antibacterial monomer DMADDM was effective in inhibiting both soluble rhMMPs and
      matrix-bound human dentin MMPs. These results, together with previous studies
      showing that adhesives containing DMADDM inhibited biofilms without compromising
      dentin bond strength, suggest that DMADDM is promising for use in adhesives to
      prevent collagen degradation in hybrid layer and protect the resin-dentin bond.

PMID- 25595565
TI  - Allopurinol and progression of CKD and cardiovascular events: long-term follow-up
      of a randomized clinical trial.
AB  - BACKGROUND: Asymptomatic hyperuricemia increases renal and cardiovascular (CV)
      risk. We previously conducted a 2-year, single-blind, randomized, controlled
      trial of allopurinol treatment that showed improved estimated glomerular
      filtration rate and reduced CV risk. STUDY DESIGN: Post hoc analysis of a long
      term follow-up after completion of the 2-year trial. SETTING & PARTICIPANTS: 113
      participants (57 in the allopurinol group and 56 in the control group) initially
      followed up for 2 years and 107 participants followed up to 5 additional years.
      INTERVENTION: Continuation of allopurinol treatment, 100mg/d, or standard
      treatment. OUTCOME: Renal event (defined as starting dialysis therapy and/or
      doubling serum creatinine and/or >=50% decrease in estimated estimated glomerular
      filtration rate) and CV events (defined as myocardial infarction, coronary
      revascularization or angina pectoris, congestive heart failure, cerebrovascular
      disease, and peripheral vascular disease). RESULTS: During initial follow-up,
      there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal
      and 15 CV events in the control group. In the long-term follow-up period, 12 of
      56 participants taking allopurinol stopped treatment and 10 of 51 control
      participants received allopurinol. During long-term follow-up, an additional 7
      and 9 participants in the allopurinol group experienced a renal or CV event,
      respectively, and an additional 18 and 8 participants in the control group
      experienced a renal or CV event, respectively. Thus, during the initial and long
      term follow-up (median, 84 months), 9 patients in the allopurinol group had a
      renal event compared with 24 patients in the control group (HR, 0.32; 95% CI,
      0.15-0.69; P=0.004; adjusted for age, sex, baseline kidney function, uric acid
      level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients
      treated with allopurinol experienced CV events compared with 23 in the control
      group (HR, 0.43; 95% CI, 0.21-0.88; P=0.02; adjusted for age, sex, and baseline
      kidney function). LIMITATIONS: Small sample size, single center, not double
      blind, post hoc follow-up and analysis. CONCLUSIONS: Long-term treatment with
      allopurinol may slow the rate of progression of kidney disease and reduce CV
      risk.

PMID- 25595566
TI  - Maternal diabetes mellitus and congenital anomalies of the kidney and urinary
      tract (CAKUT) in the child.
AB  - BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the
      primary cause of chronic kidney disease in children. The relevance of timing of
      diabetes mellitus (DM) exposure on risk of CAKUT in exposed children is unknown.
      STUDY DESIGN: Population-based nested case-control study. SETTING & PARTICIPANTS:
      Infants born between fiscal years 1996/1997 and 2009/2010 in Manitoba, Canada,
      identified using administrative data housed at the Manitoba Centre for Health
      Policy. PREDICTORS: Pregestational (including first 20 weeks' gestation) and
      gestational (>20 weeks) DM and relevant confounders (maternal age; renin
      angiotensin-aldosterone system inhibitor use; low socioeconomic status; alcohol,
      illicit drug, and smoking use during pregnancy; region of residence; and size for
      gestational age [surrogate of glycemic control]). OUTCOME: CAKUT identified by
      International Classification of Diseases codes. RESULTS: 945 case patients with
      CAKUT and 4,725 controls (matched for gestational age, sex, and birth year) were
      identified. Maternal pregestational DM occurred in 39 (4.1%) of the CAKUT group
      and 111 (2.3%) controls (P = 0.002), whereas gestational DM occurred in 40 (4.2%)
      of the CAKUT group and 157 (3.3%) controls (P = 0.2). In the conditional
      multivariable logistic regression model, pregestational DM was associated with
      CAKUT (OR, 1.67; 95% CI, 1.14-2.46), whereas gestational DM was not (OR, 1.29;
      95% CI, 0.90-1.85). Both large (LGA) and small for gestational age (SGA) also
      were associated significantly with CAKUT (LGA: OR, 1.34 [95% CI, 1.11-1.63]; SGA:
      OR, 1.59 [95% CI, 1.26-2.01]). LIMITATIONS: Lack of data for maternal glycemic
      control and body mass index. CONCLUSIONS: This study suggests that DM in the
      first 20 weeks of pregnancy is associated with CAKUT in exposed infants. The
      association between CAKUT and LGA suggests that poor glycemic control increases
      risk. Screening and intervention studies in women of childbearing age with DM are
      warranted to determine whether the risk of chronic kidney disease in children can
      be modified.

PMID- 25595567
TI  - CNV-ROC: A cost effective, computer-aided analytical performance evaluator of
      chromosomal microarrays.
AB  - Chromosomal microarrays (CMAs) are routinely used in both research and clinical
      laboratories; yet, little attention has been given to the estimation of genome
      wide true and false negatives during the assessment of these assays and how such
      information could be used to calibrate various algorithmic metrics to improve
      performance. Low-throughput, locus-specific methods such as fluorescence in situ
      hybridization (FISH), quantitative PCR (qPCR), or multiplex ligation-dependent
      probe amplification (MLPA) preclude rigorous calibration of various metrics used
      by copy number variant (CNV) detection algorithms. To aid this task, we have
      established a comparative methodology, CNV-ROC, which is capable of performing a
      high throughput, low cost, analysis of CMAs that takes into consideration genome
      wide true and false negatives. CNV-ROC uses a higher resolution microarray to
      confirm calls from a lower resolution microarray and provides for a true measure
      of genome-wide performance metrics at the resolution offered by microarray
      testing. CNV-ROC also provides for a very precise comparison of CNV calls between
      two microarray platforms without the need to establish an arbitrary degree of
      overlap. Comparison of CNVs across microarrays is done on a per-probe basis and
      receiver operator characteristic (ROC) analysis is used to calibrate algorithmic
      metrics, such as log2 ratio threshold, to enhance CNV calling performance. CNV
      ROC addresses a critical and consistently overlooked aspect of analytical
      assessments of genome-wide techniques like CMAs which is the measurement and use
      of genome-wide true and false negative data for the calculation of performance
      metrics and comparison of CNV profiles between different microarray experiments. 

PMID- 25595568
TI  - Attitudes toward transvaginal mesh among patients in a urogynecology practice.
AB  - INTRODUCTION AND HYPOTHESIS: There has been increasing media attention regarding
      transvaginal mesh (TVM). We hypothesized that new urogynecology patients have
      limited knowledge and negative opinions of TVM. METHODS: An anonymous survey was
      distributed to all new patients presenting to the Mt Auburn Hospital
      urogynecology practice from 1 November 2012 to 31 January 2013. A total of 146
      patients completed the questionnaire. The survey was designed to elicit
      information on participants' knowledge and opinions about TVM and knowledge about
      recent FDA safety communications. All statistical tests were two-sided, and P
      values <0.05 were considered statistically significant. RESULTS: Analyses were
      restricted to the 77 women who had either heard of TVM or were unsure if they had
      heard of TVM. A minority (32.5 %) of these women correctly defined TVM, and 33.8
      % had a negative impression of TVM. Respondents obtained their information on TVM
      from the media (48.1 %), the Internet (24.7 %), family or friends (22.1 %), and
      health care providers (18.2 %). The majority (71.4 %) agreed that they needed
      more information about TVM before making any decisions about using it to treat
      their condition. Nearly one quarter of respondents (23.4 %) agreed that they
      would not want their doctor to use TVM on them for any reason. When asked about
      recent FDA communications, 27.3 % of patients correctly responded that the FDA
      had released a safety communication regarding TVM. CONCLUSIONS: The majority of
      participants had limited knowledge of TVM; however, only a minority had negative
      opinions. Given our findings, it is important that providers spend more time
      during the consent process explaining TVM and its risks and benefits as a
      treatment option.

PMID- 25595569
TI  - Hollow polymer microneedles array resistance and insertion tests.
AB  - Microneedles are developed in order to become the transdermal administration
      method of the future. They however still face numerous challenges. This paper
      addresses the challenge to effectively insert the microneedle arrays into
      membranes. A recently proposed model membrane and test method for microneedles
      insertion, published in International Journal of Pharmaceutics, is used in this
      aim. A moulded 4 by 4 hollow polymer microneedle array developed at the
      Universite Libre de Bruxelles is tested for insertion using this model. Results
      show that the array is extremely resistant to insertion, it can withstand very
      high forces and even multiple insertions without blunting. Different insertion
      tests were performed on a folded in eight Parafilm(r) film because it exhibits
      excellent similarity to porcine skin. The insertion force, the insertion speed
      and the holding time of the array against membranes must be optimised in order to
      get efficient reliable insertions at, at least, 500MUm depth.

PMID- 25595571
TI  - Autoimmune liver disease in Noonan Syndrome.
AB  - Noonan Syndrome (NS) is characterized by short stature, typical facial
      dysmorphology and congenital heart defects. The incidence of NS is estimated to
      be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an
      autosomal dominant trait. In approximately 50% of cases, the disease is caused by
      missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of
      function of the non-receptor protein tyrosine phosphatase SHP-2 protein.
      Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive
      necroinflammatory liver disease. Common features of AIH are
      hypergammaglobulinemia (IgG), presence of circulating autoantibodies,
      histological picture of interface hepatitis and response to immunosuppressant
      drugs. Conventional treatment with Prednisone and Azathioprine is effective in
      most patients. We describe the case of a 6 years-old girl with Noonan Syndrome
      and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed
      heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between
      NS and autoimmune disorders is known, this is the second case of association
      between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature.
      In the management of NS, an accurate clinical evaluation would be recommended.
      When there is a clinical suspicion of autoimmune phenomena, appropriate
      laboratory tests should be performed with the aim of clarifying whether the
      immune system is involved in NS. We think that autoimmunity represents a
      characteristic of NS, even if the etiopathogenesis is still unknown.

PMID- 25595570
TI  - Preparation of an injectable depot system for long-term delivery of alendronate
      and evaluation of its anti-osteoporotic effect in an ovariectomized rat model.
AB  - We prepared an injectable depot system for the long-term delivery of alendronate
      using a solid/water/oil/water multiple emulsion technique with poly(lactic-co
      glycolic acid) as a carrier. The microparticles were spherical with smooth
      surfaces, ranging from 20 to 70 MUm in size. The microspheres (ALD-HA-RG504H
      MC70) were optimally prepared by introducing a viscous material (hyaluronic acid)
      and a co-solvent system in the inner aqueous and oil phases, respectively, and
      showed a significantly increased drug encapsulation efficacy (>70%); the initial
      burst release was <10% after 1 day. In vitro drug release from ALD-HA-RG504H-MC70
      followed zero-order kinetics for approximately 4 weeks and the alendronate plasma
      level was maintained for more than 1 month after intramuscular injection in
      rabbits. The ovariectomized (OVX) rats with ALD-HA-RG504H-MC70 injected
      intramuscularly (0.9 mg alendronate/kg/4 weeks) had 112% and 482% increased bone
      mineral density and trabecular area in the tibia than the OVX controls,
      respectively, and showed significant improvements in trabecular microarchitecture
      and bone strength. Furthermore, the major biomarkers of bone turnover revealed
      that ALD-HA-RG504H-MC70 suppressed effectively the progression of osteoporosis
      and facilitated new bone formation. Therefore, this sustained release depot
      system may improve patient compliance and therapeutic efficacy by reducing dose
      amounts and frequency with minimal adverse reactions.

PMID- 25595572
TI  - Molecular cytogenetic characterization of a familial pericentric inversion 3
      associated with short stature.
AB  - Short stature refers to the height of an individual which is below expected. The
      causes are heterogenous and influenced by several genetic and environmental
      factors. Chromosomal abnormalities are a major cause of diseases and cytogenetic
      mapping is one of the powerful tools for the identification of novel disease
      genes. Here we report a three generation family with a heterozygous pericentric
      inversion of 46, XX, inv(3) (p24.1q26.1) associated with Short stature.
      Positional cloning strategy was used to physically map the breakpoint regions by
      Fluorescence in situ hybridization (FISH). Fine mapping was performed with
      Bacterial Artificial Chromosome (BAC) clones spanning the breakpoint regions. In
      order to further characterize the breakpoint regions extensive molecular mapping
      was carried out with the breakpoint spanning BACs which narrowed down the
      breakpoint region to 2.9 kb and 5.3 kb regions on p and q arm respectively.
      Although these breakpoints did not disrupt any validated genes, we had identified
      a novel putative gene in the vicinity of 3q26.1 breakpoint region by in silico
      analysis. Trying to find the presence of any transcripts of this putative gene we
      analyzed human total RNA by RT-PCR and identified transcripts containing three
      new exons confirming the existence of a so far unknown gene close to the 3q
      breakpoint.

PMID- 25595573
TI  - Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin
      disorder.
AB  - The cobalamin type C deficiency is a rare condition that results from impaired
      biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl).
      Hemizygous mutations of the HCFC1 gene explain the majority of clinically and
      biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We
      report a family with two maternal half-brothers with multiple congenital
      anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with
      dysmorphic features (flat profile, cleft lip for one), increased nuchal
      translucency, prenatal onset microcephaly and hypospadias. Additionally to early
      onset intractable epilepsy and profound neurocognitive impairment, this familial
      observation suggests that HCFC1 gene should be considered in boys with midline
      malformations, even without proven cobalamin C deficiency.

PMID- 25595575
TI  - Renin-angiotensin system (RAS) blockade attenuates growth and metastatic
      potential of renal cell carcinoma in mice.
AB  - OBJECTIVES: Renal cell carcinoma (RCC) is the most frequent type of cancer among
      renal neoplasms in adults and responds poorly to radiotherapy and chemotherapy.
      There is evidence that blockade of the renin-angiotensin system (RAS) might have
      antineoplastic effects. The aim of this study was to investigate the effects of
      RAS blockade on RCC in a murine model. METHODS AND MATERIALS: Murine renal cancer
      cells (Renca) were injected (1 * 10(5)) into the subcapsular space of the left
      kidney of BALB/c mice (8 wk of age). The animals were divided into 4 groups: a
      control group (no treatment), angiotensin-receptor blockers group (losartan
      100mg/kg/d), angiotensin-converting enzyme inhibitor group (captopril 10mg/kg/d),
      and angiotensin-receptor blockers +angiotensin-converting enzyme inhibitor group
      (losartan 100mg/kg/d +captopril 10mg/kg/d). The animals received the drugs by
      gavage for 21 days after inoculation, beginning 2 days before tumor induction,
      and were then euthanized. After killing the animals, the kidneys and lungs were
      removed, weighed, and processed for histopathological and immunohistochemical
      analyses. Angiogenesis and vascular microvessels were assessed with the
      antibodies anti-vascular endothelial growth factor and anti-CD34. RESULTS:
      Angiotensin II-inoculated animals developed renal tumors. Treated animals
      presented smaller tumors, regardless of the therapeutic regimen, and far fewer
      lung metastases in both quantity and dimension compared with the controls. The
      expression of vascular endothelial growth factor and CD34 were significantly
      decreased in renal tumors of treated animals compared with the controls.
      CONCLUSIONS: Our findings suggest that blockade of RAS decreases tumor
      proliferation and metastatic capacity of RCC in this experimental model.

PMID- 25595574
TI  - Child neuroanatomical, neurocognitive, and visual acuity outcomes with maternal
      opioid and polysubstance detoxification.
AB  - BACKGROUND: Maternal opioid and polysubstance use during pregnancy is associated
      with an increased risk of child neurocognitive and visual problems and
      neuroanatomical differences. We hypothesized that, in contrast to findings from a
      previous study of children born to mothers not detoxified, children born to
      detoxified mothers would not show gross neuroanatomical and neurocognitive
      differences. METHODS: Mothers with opioid and polysusbstance abuse problems and
      their infants (n = 11 + 12) were recruited from residential treatment
      institutions. Comparison mothers and infants (n = 12 + 12) were recruited from
      child health centers. The studies were approved by the Regional Committee of
      Medical Research Ethics. Children had magnetic resonance imaging scanning,
      neurocognitive, and visual acuity testing at 4.5 years. Neuroanatomical,
      cognitive, and visual acuity characteristics were compared across groups by
      analysis of variance and general linear models. RESULTS: There were no
      significant differences across groups in neuroanatomical volumes, or cortical
      thickness, area, or volume. There were no differences in general neurocognitive
      functioning, but significantly lower left eye visual acuity, and a trend toward
      lower binocular visual acuity, in the drug-exposed relative to the comparison
      group. CONCLUSIONS: The present study does not demonstrate gross differences
      relative to a comparison group in neuroanatomical and general neurocognitive
      characteristics of children born to mothers with opioid and polysubstance abuse
      who were detoxified during pregnancy. However, visual acuity was significantly
      lower in the drug-exposed group, requiring attention. There is a pressing need
      for additional and larger studies of long-term and specific child outcomes in
      this at-risk group.

PMID- 25595576
TI  - Low circulating free and bioavailable testosterone levels as predictors of high
      grade tumors in patients undergoing radical prostatectomy for localized prostate
      cancer.
AB  - OBJECTIVE: Controversy exists regarding the propensity of hypogonadism and
      metabolic disorders to promote the development of high-risk prostate cancer
      (PCa). Our aim was to prospectively test whether preoperative circulating
      testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with
      aggressive pathological features after radical prostatectomy (RP). MATERIAL AND
      METHODS: Overall, 354 patients undergoing robot-assisted RP at our academic
      institution, between 2010 and 2013, to treat clinically localized PCa were
      included in this prospective study. Pelvic lymphadenectomy was performed in 116
      (32.8%) patients and confirmed the absence of nodal metastases in all of them.
      Cardiovascular risk factors and body-mass index (BMI) were used to define MetS
      and obesity, respectively. Total testosterone (TT) levels were assessed using an
      immunoassay method, whereas bioavailable testosterone (BT) and free testosterone
      (FT) levels were estimated using Vermeulen's formula. Multivariate logistic
      regression analyses assessed independent predictors for postoperative aggressive
      pathological features (i.e., a pathological Gleason score [GS] >= 7,
      extracapsular extension [ECE], seminal vesicle invasion [SVI], and positive
      surgical margins [PSM]) and GS upgrading. RESULTS: Low TT, BT, and FT levels were
      found in 54 (15.2%), 70 (19.8%), and 62 (17.5%) patients, respectively. Median
      BMI was 26.3 kg/m(2) (range: 17.4-43.9), and prevalence of MetS was 18.9%.
      Significantly higher rates of pathological GS >= 7 were observed in groups with a
      low TT level (46.3% vs. 33.3%; P = 0.01), low BT level (44.3% vs. 33.1%;
      P<0.001), and low FT level (46.8% vs. 32.9%; P = 0.001). Multivariate analyses
      demonstrated that only low BT and FT levels were independent predictors of
      pathological GS >= 7 (odds ratio [OR] = 1.76; P<0.001 and OR = 1.39; P<0.001,
      respectively) and GS upgrading (OR = 2.82; P<0.001 and OR = 1.71; P<0.001,
      respectively), but there was no significant correlation between low circulating
      testosterone levels and ECE, SVI, or PSM. Furthermore, BMI (OR = 1.28; P = 0.04)
      and MetS (OR = 1.19; P = 0.01) were only correlated with PSM. CONCLUSION:
      Hypogonadism, obesity, and MetS were not independent predictors of pathological
      GS >= 7, ECE, or SVI after RP. Our data suggest that only low BT and FT levels,
      which might logically result in an active androgen-depleted environment, were
      linked with high-grade PCa.

PMID- 25595577
TI  - Clinical phenotypes associated with circulating tumor cell enumeration in
      metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: The presence of >=5 circulating tumor cells (CTCs) is prognostic for
      shorter survival in men with metastatic castration-resistant prostate cancer
      (mCRPC). However, some men have low CTCs despite widespread disease, suggesting
      heterogeneity in CTC phenotype or detection. The aim of this study was to
      evaluate the association of CTC enumeration with clinical disease characteristics
      and overall survival in men with mCRPC at our institution. DESIGN: CTCs were
      enumerated using the CellSearch method in a prospective correlative study in men
      with mCRPC starting a new systemic therapy. The primary objective was to
      determine the clinical phenotype of the subset of men with mCRPC who have a poor
      prognosis and low CTCs. Secondary end points included associations of CTCs with
      survival and known prognostic biomarkers, before therapy and at progression.
      RESULTS: At baseline, median CTC count was 16 cells and prostate-specific antigen
      (PSA) level was 178 ng/ml. At progression, median CTC count was 42, PSA level was
      245 ng/ml, levels of lactate dehydrogenase and alkaline phosphatase rose, and
      level of hemoglobin dropped. The median overall survival for this heavily
      pretreated population was 11.2 months, and the multivariable hazard ratio for
      death of men with CTCs<5 vs.>=5 was 0.43 (95% CI: 0.24-0.77). Median progression
      free survival was 4.4 months. CTC enumeration modestly correlated with lactate
      dehydrogenase and alkaline phosphatase levels but only weakly correlated with PSA
      and hemoglobin levels. We were unable to identify a consistent subgroup of poor
      prognosis men with a low number of CTCs. CONCLUSION: CTC enumeration appears to
      be prognostic in men with mCRPC and describes a phenotype of hematogenous
      dissemination that cannot be predicted based on standard clinical and laboratory
      assessments.

PMID- 25595578
TI  - Curcumin ameliorates high glucose-induced neural tube defects by suppressing
      cellular stress and apoptosis.
AB  - OBJECTIVE: Curcumin is a naturally occurring polyphenol present in the roots of
      the Curcuma longa plant (turmeric), which possesses antioxidant, antitumorigenic,
      and antiinflammatory properties. Here, we test whether curcumin treatment reduces
      high glucose-induced neural tube defects (NTDs), and if this occurs via blocking
      cellular stress and caspase activation. STUDY DESIGN: Embryonic day 8.5 mouse
      embryos were collected for use in whole-embryo culture under normal (100 mg/dL)
      or high (300 mg/dL) glucose conditions, with or without curcumin treatment. After
      24 hours in culture, protein levels of oxidative stress makers, nitrosative
      stress makers, endoplasmic reticulum (ER) stress makers, cleaved caspase 3 and 8,
      and the level of lipid peroxides were determined in the embryos. After 36 hours
      in culture, embryos were examined for evidence of NTD formation. RESULTS:
      Although 10 MUmol/L of curcumin did not significantly reduce the rate of NTDs
      caused by high glucose, 20 MUmol/L of curcumin significantly ameliorated high
      glucose-induced NTD formation. Curcumin suppressed oxidative stress in embryos
      cultured under high glucose conditions. Treatment reduced the levels of the lipid
      peroxidation marker, 4-hydroxynonenal, nitrotyrosine-modified protein, and lipid
      peroxides. Curcumin also blocked ER stress by inhibiting phosphorylated protein
      kinase RNA-like ER kinase, phosphorylated inositol-requiring protein-1alpha (p
      IRE1alpha), phosphorylated eukaryotic initiation factor 2alpha (p-eIF2alpha),
      C/EBP-homologous protein, binding immunoglobulin protein, and x-box binding
      protein 1 messenger RNA splicing. Additionally, curcumin abolished caspase 3 and
      caspase 8 cleavage in embryos cultured under high glucose conditions. CONCLUSION:
      Curcumin reduces high glucose-induced NTD formation by blocking cellular stress
      and caspase activation, suggesting that curcumin supplements could reduce the
      negative effects of diabetes on the embryo. Further investigation will be needed
      to determine if the experimental findings can translate into clinical settings.

PMID- 25595580
TI  - Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis.
AB  - OBJECTIVE: Postpartum infections are polymicrobial and typically include
      Ureaplasma, an intracellular microbe that is treated by macrolides such as
      azithromycin. The aim of this study was to evaluate the perinatal
      pharmacokinetics of azithromycin after a single preincision dose before cesarean
      delivery. STUDY DESIGN: Thirty women who underwent scheduled cesarean delivery
      were assigned randomly to receive 500 mg of intravenous azithromycin that was
      initiated 15, 30, or 60 minutes before incision and infused over 1 hour. Serial
      maternal plasma samples were drawn from the end of infusion up to 8 hours after
      the infusion. Samples of amniotic fluid, umbilical cord blood, placenta,
      myometrium, and adipose tissue were collected intraoperatively. Breast milk
      samples were collected 12-48 hours after the infusion in 8 women who were
      breastfeeding. Azithromycin was quantified with high performance liquid
      chromatography separation coupled with tandem mass spectrometry detection. Plasma
      pharmacokinetic parameters were estimated with the use of noncompartmental
      analysis and compartmental modeling and simulations. RESULTS: The maximum
      maternal plasma concentration was reached within 1 hour and exceeded the in vitro
      minimum inhibitory concentration (MIC50) of 250 ng/mL of Ureaplasma spp in all 30
      patients. The concentrations were sustained with a half-life of 6.7 hours. The
      median concentration of azithromycin in adipose tissue was 102 ng/g, which was
      below the MIC50. The median concentration in myometrium was 402 ng/g, which
      exceeded the MIC50. Azithromycin was detectable in both the umbilical cord plasma
      and amniotic fluid after the single preoperative dose. Azithromycin
      concentrations in breast milk were high and were sustained up to 48 hours after
      the single dose. Simulations demonstrated accumulation in breast milk after
      multiple doses. CONCLUSION: A single dose of azithromycin achieves effective
      plasma and tissue concentrations and is transported rapidly across the placenta.
      The tissue concentrations that are achieved in the myometrium exceed the MIC50
      for Ureaplasma spp.

PMID- 25595582
TI  - Analysis of urinary TGF-beta1, MCP-1, NGAL, and IL-17 as biomarkers for lupus
      nephritis.
AB  - This study was aimed to determine the diagnostic performance of transforming
      growth factor beta 1 (uTGF-beta1), monocyte chemoattractant protein-1 (uMCP-1),
      neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 17 (uIL-17) in
      LN. Seventy participants were studied, categorized into three groups: 38 severe
      LN (class III-IV LN patients); 12 mild LN (class I-II LN patients); and 20
      control (healthy volunteers). Diagnosis of SLE was based on the 1997 ARA
      criteria. Class NL classified according to ISN/RPS 2004. uTGF-beta1, uMCP-1,
      uNGAL, uIL-17 levels were determined by ELISA, using spot urine. The level of
      uMCP-1 and uNGAL was significantly greater in severe or mild LN compared with
      control group (P<0.05). The level of uTGF-beta1 and uIL-17 was significantly
      higher in severe LN than that controls group (P<0.05). The AUC of uTGF-beta1,
      uMCP-1, uNGAL, uIL-17 was 66.50%; 86.90%; 87.50%; 71.70%, with the cut-off value
      of 27.13pg/ml; 1.54pg/ml; 446.30pg/ml; 36.62pg/ml. Only uNGAL showed a
      significant correlation with the activity (P=0.016; r=0.389) and chronicity
      indices (P=0.018; r=0.381). This study showed that uTGF-beta1, uMCP-1, uNGAL, uIL
      17 levels were increased in LN. The AUC values for each biomarker are indicating
      a good diagnostic value. Urinary NGAL had the best sensitivity and specificity
      followed by uMCP-1, uIL-17 and uTGF-beta1. For combinations of two biomarkers,
      the best sensitivity and specificity were displayed by the combination of uTGF
      beta1 & u-NGAL, followed by uMCP-1 & uNGAL. 

PMID- 25595583
TI  - Insights from the molecular docking of hydrolytic products of methyl iso cyanate
      (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 methyl isocyanate (MIC) i.e. dimethyl
      urea, trimethyl urea and trimethyl isocyanurate was docked to different human
      immune proteins against Mtb using autodock 4.0. Results shows that all hydrolytic
      product (dimethyl urea, trimethyl urea and trimethylisocyanurate) strongly
      inhibits to CD40 ligand and their binding energies were found to be DeltaG -3.51,
      -3.79, -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 maximum inhibited by trimethylisocyanurate, has a role in
      the macrophage activation for the destruction of Mycobacterium tuberculosis. The
      present study may lead to better understanding of human immune protein inhibition
      by hydrolytic product of methyl isocyanate (MIC).

PMID- 25595579
TI  - Oxidative stress is responsible for maternal diabetes-impaired transforming
      growth factor beta signaling in the developing mouse heart.
AB  - OBJECTIVE: Oxidative stress plays a causal role in diabetic embryopathy. Maternal
      diabetes induces heart defects and impaired transforming growth factor beta
      (TGFbeta) signaling, which is essential for cardiogenesis. We hypothesize that
      mitigating oxidative stress through superoxide dismutase 1 (SOD1) overexpression
      in transgenic (Tg) mice reverses maternal hyperglycemia-impaired TGFbeta
      signaling and its downstream effectors. STUDY DESIGN: Day 12.5 embryonic hearts
      from wild-type (WT) and SOD1 overexpressing embryos of nondiabetic (ND) and
      diabetic mellitus (DM) dams were used for the detection of oxidative stress
      markers: 4-hydroxynonenal (4-HNE) and malondlaldehyde (MDA), and TGFbeta1, 2, and
      3, phosphor (p)-TGFbeta receptor II (TbetaRII), p-phosphorylated mothers against
      decapentaplegic (Smad)2, and p-Smad3. The expression of 3 TGFbeta-responsive
      genes was also assessed. Day 11.5 embryonic hearts were explanted and cultured ex
      vivo, with or without treatments of a SOD1 mimetic (Tempol; Enzo Life Science,
      Farmingdale, NY) or a TGFbeta recombinant protein for the detection of TGFbeta
      signaling intermediates. RESULTS: Levels of 4-HNE and MDA were significantly
      increased by maternal diabetes, and SOD1 overexpression blocked the increase of
      these 2 oxidative stress markers. Maternal diabetes suppresses the TGFbeta
      signaling pathway by down-regulating TGFbeta1 and TGFbeta3 expression.
      Consequently, phosphorylation of TbetaRII, Smad2, and Smad3, downstream effectors
      of TGFbeta, and expression of 3 TGFbeta-responsive genes were reduced by maternal
      diabetes, and these reductions were prevented by SOD1 overexpression. Treatment
      with Tempol or TGFbeta recombinant protein restored high-glucose-suppressed
      TGFbeta signaling intermediates and responsive gene expression. CONCLUSION:
      Oxidative stress mediates the inhibitory effect of hyperglycemia in the
      developing heart. Antioxidants, TGFbeta recombinant proteins, or TGFbeta agonists
      may have potential therapeutic values in the prevention of heart defects in
      diabetic pregnancies.

PMID- 25595584
TI  - Computational analysis and In-silico predictive modeling for inhibitors of PhoP
      regulon in S. typhi on high-throughput screening bioassay dataset.
AB  - The 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 to the resistance formation that would be used as drug for
      the treatment of salmonellosis particularly typhoid fever. The PhoP regulon is
      well studied and have now been shown to be critical regulator of number of gene
      expression whose 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 as therapeutically. Although the discovery process of biologically
      active compounds for the treatment of typhoid rely 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 become available that gives ample growth of diverse
      compound library, but the time and endeavor required to screen these unfocused
      massive and diverse library has been slightly reduced in the past years. Hence
      there is demand to improve the high quality hits and success rate for high
      throughput screening (HTS) that required focused and biased compound library
      towards the particular target. Therefore we still need an advantageous and
      expedient method to prioritize the molecules that will be utilized for biological
      screens which save time and 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
      towards find out the privileged scaffold.

PMID- 25595585
TI  - Cross family comparative proteomic study and molecular phylogeny of MAP kinases
      in plants.
AB  - Mitogen-activated protein kinases are serine/threonine-specific protein kinases
      and they are closely related to cyclin-dependent kinases. They constitute
      functionally significant family of proteins that is involved in various cellular
      functions like response to mitogens, osmotic stress, heat shock and
      proinflammatory cytokines as well as known to play key role in proliferation,
      gene expression, differentiation, mitosis, cell survival, and apoptosis. MAP
      kinases are characteristically found in eukaryotes only, though they are fairly
      diverse and encountered in all animals, fungi and plants, and even in an array of
      unicellular eukaryotes. In this study 24 MAP kinase sequences from various plant
      species were selected in order to compare their conserved regions, amino acid
      composition, evolutionary orders and other statistical parameters.

PMID- 25595586
TI  - Examining the variations in the results of the Hotelling T2 test in case of
      changing baseline landmarks in the Bookstein coordinates.
AB  - In many biological and biomedical investigations, the most effective way to
      analyze the forms of whole biological organs or organisms is by recording
      geometric locations of landmark points. If we want to compare shapes, then
      individuals should be translated, rotated and scaled in such a way that all of
      the individuals lie in a standard position and are centered. Bookstein conducted
      this process by choosing two landmarks as reference landmarks. Each individual is
      translated, rotated and scaled according to these reference landmarks. The aim of
      the present study is to examine the change in the p values in the case of
      choosing different baseline landmarks when performing the Hotelling T 2 test,
      which is commonly used when comparing two sample shape configurations based on
      Bookstein coordinates. For this purpose, the changes in the p values were
      investigated in shape configurations that are composed of a different number of
      landmarks by taking all of the possible paired landmark combinations at different
      variance levels and sample sizes. As a result of the present study, it was
      observed that, with the increase in the landmark number, the number of possible
      baseline landmark combinations also increases and, for this reason, a substantial
      number of variations occur in the p values. Therefore, it is an important to
      decide which landmarks should be taken as reference landmarks when using the
      Bookstein coordinates.

PMID- 25595587
TI  - Examining the efficiency of models using tangent coordinates or principal
      component scores in allometry studies.
AB  - Most of the studies in medical and biological sciences are related with the
      examination of geometrical properties of an organ or organism. Growth and
      allometry studies are important in the way of investigating the effects of
      diseases and the environmental factors effects on the structure of the organ or
      organism. Thus statistical shape analysis has recently become more important in
      the medical and biological sciences. Shape is all geometrical information that
      remains when location, scale and rotational effects are removed from an object.
      Allometry, which is a relationship between size and shape, plays an important
      role in the development of statistical shape analysis. The aim of the present
      study was to compare two different models for allometry which includes tangent
      coordinates and principal component scores of tangent coordinates as dependent
      variables in multivariate regression analysis. The results of the simulation
      study showed that, the model constructed by taking tangent coordinates as
      dependent variables is more appropriate than the model constructed by taking
      principal component scores of tangent coordinates as dependent variables, for all
      sample sizes.

PMID- 25595581
TI  - Advances in revealing the molecular targets downstream of oxidative stress
      induced proapoptotic kinase signaling in diabetic embryopathy.
AB  - Preexisting maternal diabetes is a high-risk factor of diabetic embryopathy, such
      as neural tube defects and congenital heart defects. Maternal diabetes
      significantly increases the production of reactive oxygen species, resulting in
      oxidative stress and diabetic embryopathy. Multiple cellular and metabolic
      factors contribute to these processes. Forkhead box O (FoxO)-3a has been
      demonstrated as a key transcription factor in the signaling transduction pathways
      responsible for maternal diabetes-induced birth defects. Apoptosis signal
      regulating kinase 1 (ASK1) activated by oxidative stress stimulates nuclear
      translocation of FoxO3a, resulting in the overexpression of tumor necrosis factor
      receptor 1-associated death domain protein, which, in turn, leads to caspase-8
      activation and apoptosis. Maternal diabetes-activated c-Jun N-terminal kinase
      (JNK)-1/2, downstream effectors of ASK1, can be blocked by superoxide dismutase-1
      overexpression, suggesting that oxidative stress is responsible for JNK1/2
      signaling activation. Deletion of JNK1/2 significantly suppressed the activity of
      FoxO3a. These observations indicate that maternal diabetes-induced oxidative
      stress stimulates the activation of ASK1, JNK1/2, FoxO3a, tumor necrosis factor
      receptor 1-associated death domain protein, caspase-8 cleavage, and finally,
      apoptosis and diabetic embryopathy. 

PMID- 25595588
TI  - QM/MM MD and free energy simulation study of methyl transfer processes catalyzed
      by PKMTs and PRMTs.
AB  - Methyl transfer processes catalyzed by protein lysine methyltransferases (PKMTs)
      and protein arginine methyltransferases (PRMTs) control important biological
      events including transcriptional regulation and cell signaling. One important
      property of these enzymes is that different PKMTs and PRMTs catalyze the
      formation of different methylated product (product specificity). These different
      methylation states lead to different biological outcomes. Here we review the
      results of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD)
      and free energy simulations that have been performed to study the reaction
      mechanism of PKMTs and PRMTs and the mechanism underlying the product specificity
      of the methyl transfer processes.

PMID- 25595591
TI  - DNMT1 and EZH2 mediated methylation silences the microRNA-200b/a/429 gene and
      promotes tumor progression.
AB  - Aberrant expression of the microRNA-200 (miR-200) family has been linked to the
      occurrence and development of various types of malignant tumors, including
      hepatocellular carcinoma (HCC), colon cancer and breast cancer. However, little
      is known about the precise mechanism by which miR-200 expression is
      downregulated. The intricate relationship between DNA methylation and histone
      modifications has become a subject of increasing interest. The expression of miR
      200 family members is modified by similar or complementary epigenetic mechanisms
      in MGC-803 and BGC-823 gastric cancer cells and U87 MG glioma cells. Chromatin
      immunoprecipitation assays revealed that DNA methyltransferase 1 (DNMT1) bound to
      miR-200b/a/429 promoter regions, indicating an interaction between DNMT1 and the
      miR-200b/a/429 promoter. Furthermore, Co-Immunoprecipitation (Co-IP) detection
      showed that DNMT1, together with the PcG protein Enhancer of Zeste homolog 2
      (EZH2), a histone methyltransferase, contributed to the transcriptional
      repression of microRNA-200 family members. Knockdown of EZH2 not only impacted
      H3K27 trimethylation but also reduced DNMT1 presence on the miR-200b/a/429
      promoter. EZH2 appeared to be essential for DNMT1 recruitment to the promoter
      region. Silencing EZH2 and DNMT1 using drugs or RNA interference dramatically
      reduced the levels of miR-200b/a/429 expression. Collectively, these results
      indicated that EZH2 and DNMT1-mediated epigenetic silencing contributed to the
      progression of gastric cancer and glioblastoma, and therefore represents a novel
      therapeutic target for malignant tumors. 

PMID- 25595592
TI  - Failed back surgery syndrome: who has failed?
AB  - INTRODUCTION: Failed back surgery syndrome (FBSS) results from a cascade of
      medical and surgical events that lead to or leave the patient with chronic back
      and radicular pain. This concept is extremely difficult to understand, both for
      the patient and for the therapist. The difficulty is related to the connotations
      of failure and blame directly associated with this term. The perception of the
      medical situation varies enormously according to the background and medical
      education of the clinician who manages this type of patient. Eight health system
      experts (2 pain physicians, 1 orthopaedic spine surgeon, 1 neuro spine surgeon, 1
      functional neurosurgeon, 1 physiatrist, 1 psychologist and one health-economic
      expert) were asked to define and share their specialist point of view concerning
      the management of postoperative back and radicular pain. Ideally, it could be
      proposed that the patient would derive optimal benefit from systematic
      confrontation of these various points of view in order to propose the best
      treatment option at a given point in time to achieve the best possible care
      pathway. CONCLUSION: The initial pejorative connotation of FBSS suggesting
      failure or blame must now be replaced to direct the patient and therapists
      towards a temporal concept focusing on the future rather than the past. In
      addition to the redefinition of an optimised care pathway, a consensus based on
      consultation would allow redefinition and renaming of this syndrome in order to
      ensure a more positive approach centered on the patient.

PMID- 25595593
TI  - Treatment of esthesioneuroblastoma: a double approach?

PMID- 25595590
TI  - Chemokine-mediated inflammation in the degenerating retina is coordinated by
      Muller cells, activated microglia, and retinal pigment epithelium.
AB  - BACKGROUND: Monocyte infiltration is involved in the pathogenesis of many retinal
      degenerative conditions. This process traditionally depends on local expression
      of chemokines, though the roles of many of these in the degenerating retina are
      unclear. Here, we investigate expression and in situ localization of the broad
      chemokine response in a light-induced model of retinal degeneration. METHODS:
      Sprague-Dawley (SD) rats were exposed to 1,000 lux light damage (LD) for up to 24
      hrs. At time points during (1 to 24 hrs) and following (3 and 7 days) exposure,
      animals were euthanized and retinas processed. Microarray analysis assessed
      differential expression of chemokines. Some genes were further investigated using
      polymerase chain reaction (PCR) and in situ hybridization and contrasted with
      photoreceptor apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end
      labeling (TUNEL). Recruitment of retinal CD45 (+) leukocytes was determined via
      fluorescence activated cell sorting (FACS), and expression of chemokine receptors
      determined using PCR. RESULTS: Exposure to 24 hrs of LD resulted in differential
      expression of chemokines including Ccl3, Ccl4, Ccl7, Cxcl1, and Cxcl10. Their
      upregulation correlated strongly with peak photoreceptor death, at 24 hrs
      exposure. In situ hybridization revealed that the modulated chemokines were
      expressed by a combination of Muller cells, activated microglia, and retinal
      pigment epithelium (RPE). This preceded large increases in the number of CD45(+)
      cells at 3- and 7-days post exposure, which expressed a corresponding repertoire
      of chemokine receptors. CONCLUSIONS: Our data indicate that retinal degeneration
      induces upregulation of a broad chemokine response whose expression is
      coordinated by Muller cells, microglia, and RPE. The findings inform our
      understanding of the processes govern the trafficking of leukocytes, which are
      contributors in the pathology of retinal degenerations.

PMID- 25595594
TI  - Long-term stabilization by radiosurgery of a secondary focal anaplastic
      transformation in a surgically treated WHO grade II oligodendroglioma. A case
      report.
AB  - We report on a young woman with a left temporal diffuse low-grade glioma treated
      initially by a subtotal resection. A focal anaplastic area appeared 5years later
      and was treated by radiosurgery. A long-time stabilization was therefore obtained
      and lasted even after pregnancy, which is a known factor of faster tumour
      progression. This report shows that radiosurgery could be an option in the
      multimodal treatment of a selected group of patients with focal malignant
      transformation of diffuse low-grade glioma. It could permit long-term
      stabilization of the tumour without any other adjuvant treatment and without
      compromising the quality of life. 

PMID- 25595595
TI  - Sphingolipid metabolism in colorectal adenomas varies depending on histological
      architecture of polyps and grade of nuclear dysplasia.
AB  - Incidence of colorectal cancer (CRC) is growing worldwide. Pathogenetic
      mechanisms responsible for its onset and progression need further clarification.
      Colorectal adenomatous polyps are precancerous lesions with malignant potential
      dependent on histological architecture and grade of nuclear dysplasia. One of the
      factors conditioning CRC development are abnormalities in sphingolipid
      metabolism. The aim of this study was to assess the levels of sphingolipids in
      human colorectal adenomas. The control group (C, n = 12) consisted of patients
      with no colonic polyps. The examined group consisted of patients with prior
      diagnosed colonic polyps, qualified to endoscopic polypectomy. This group was
      further divided due to histological architecture into tubular adenomas group (TA,
      n = 10), tubulovillous adenomas with low-grade dysplasia (LGD-TVA, n = 10), and
      tubulovillous adenomas group with high-grade dysplasia (HGD-TVA, n = 11). In
      tissue samples, sphingolipd metabolite contents were measured using high
      performance liquid chromatography (HPLC). In cases of polypoid lesions with low
      malignancy potential (tubular adenomas), concentration of ceramide, which is
      characterized by proapoptotic and anti-proliferative properties, increases
      compared with control group (p < 0.05), whereas content of sphingosine-1
      phosphate with anti-apoptotic and stimulating cellular proliferation properties
      is reduced in comparison with control group (p < 0.05). On the contrary, in cases
      of more advanced form of adenomatous polyps (tubulovillous adenomas with high
      grade dysplasia), the ceramide level decreases compared with control group (p <
      0.05) while sphingosine-1-phosphate concentration is elevated (p < 0.05). We
      found that concentrations of pro-apoptotic ceramide are decreased and pro
      proliferative S1P levels are increased in polypoid lesions with high malignancy
      potential, and it was the opposite in those with low malignancy potential. 

PMID- 25595596
TI  - How supportive supervision influences immunization session site practices: a
      quasi-experimental study in Odisha, India.
AB  - BACKGROUND: Routine immunization (RI) is a key child survival intervention.
      Ensuring acceptable standards of RI service delivery is critical for optimal
      outcomes. Accumulated evidences suggest that 'supportive supervision' improves
      the quality of health care services in general. During 2009-2010, the Government
      of Odisha and UNICEF jointly piloted this strategy in four districts to improve
      RI program outcomes. The present study aims to assess the effect of this strategy
      on improvement of skills and practices at immunization session sites. DESIGN: A
      quasi-experimental 'post-test only' study design was adopted to compare the
      opinion and practices of frontline health workers and their supervisors in four
      intervention districts (IDs) with two control districts (CDs). Altogether, we
      interviewed 111 supervisor-supervisee (health worker) pairs using semi-structured
      interview schedules and case vignettes. We also directly observed health workers'
      practices during immunization sessions at 111 sites. Data were analyzed with SPSS
      version 16.0. RESULTS: The mean knowledge score of supervisors in CDs was
      significantly higher than in intervention groups. Variegated responses were
      obtained on case vignettes. The control group performed better in solving certain
      hypothetically asked problems, whereas the intervention group scored better in
      others. Health workers in IDs gave a lower rating to their respective
      supervisors' knowledge, skill, and frequency of supervision. Logistics and
      vaccine availability were better in CDs. CONCLUSION: Notwithstanding other
      limitations, supportive supervision may not have independent effects on improving
      the quality of immunization services. Addressing systemic issues, such as the
      availability of essential logistics, supply chain management, timely indenting,
      and financial resources, could complement the supportive supervision strategy in
      improving immunization service delivery.

PMID- 25595597
TI  - A long-standing mystery solved: the formation of 3-hydroxydesloratadine is
      catalyzed by CYP2C8 but prior glucuronidation of desloratadine by UDP
      glucuronosyltransferase 2B10 is an obligatory requirement.
AB  - Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin),
      is a nonsedating long-lasting antihistamine that is widely used for the treatment
      of allergic rhinitis and chronic idiopathic urticaria. For over 20 years, it has
      remained a mystery as to which enzymes are responsible for the formation of 3
      hydroxydesloratadine, the major active human metabolite, largely due to the
      inability of any in vitro system tested thus far to generate this metabolite. In
      this study, we demonstrated that cryopreserved human hepatocytes (CHHs) form 3
      hydroxydesloratadine and its corresponding O-glucuronide. CHHs catalyzed the
      formation of 3-hydroxydesloratadine with a Km of 1.6 MUM and a Vmax of 1.3
      pmol/min per million cells. Chemical inhibition of cytochrome P450 (P450) enzymes
      in CHHs demonstrated that gemfibrozil glucuronide (CYP2C8 inhibitor) and 1
      aminobenzotriazole (general P450 inhibitor) inhibited 3-hydroxydesloratadine
      formation by 91% and 98%, respectively. Other inhibitors of CYP2C8 (gemfibrozil,
      montelukast, clopidogrel glucuronide, repaglinide, and cerivastatin) also caused
      extensive inhibition of 3-hydroxydesloratadine formation (73%-100%). Assessment
      of desloratadine, amodiaquine, and paclitaxel metabolism by a panel of individual
      CHHs demonstrated that CYP2C8 marker activity robustly correlated with 3
      hydroxydesloratadine formation (r(2) of 0.70-0.90). Detailed mechanistic studies
      with sonicated or saponin-treated CHHs, human liver microsomes, and S9 fractions
      showed that both NADPH and UDP-glucuronic acid are required for 3
      hydroxydesloratadine formation, and studies with recombinant UDP
      glucuronosyltransferase (UGT) and P450 enzymes implicated the specific
      involvement of UGT2B10 in addition to CYP2C8. Overall, our results demonstrate
      for the first time that desloratadine glucuronidation by UGT2B10 followed by
      CYP2C8 oxidation and a deconjugation event are responsible for the formation of 3
      hydroxydesloratadine. 

PMID- 25595598
TI  - Characterization of chrysin glucuronidation in UGT1A1-overexpressing HeLa cells:
      elucidating the transporters responsible for efflux of glucuronide.
AB  - Active transport of glucuronide out of cells is a critical process in elimination
      of drugs via the glucuronidation pathway. Here, HeLa cells were stably
      transfected with UGT1A1 and the contributions of BCRP and MRP family transporters
      to the cellular efflux of chrysin glucuronide (CG) were determined. The cDNA of
      UGT1A1 was introduced into HeLa cells using the lentiviral transfection method.
      The modified cells were functional in generation of the glucuronide from chrysin.
      Ko143 at 10-20 MUM (a dual inhibitor of BCRP and UGT1A1) caused a marked decrease
      (51.3%-59.7%, P < 0.01) in the excretion rate and efflux clearance of CG.
      Likewise, MK-571 at 5-20 MUM (an inhibitor of MRPs but an activator of UGT1A1)
      resulted in a significant reduction in the excretion rate (18.2%-64.0%, P < 0.01)
      and efflux clearance (37.0%-90.2%, P < 0.001). By contrast, dipyridamole and
      leukotriene C4 showed no inhibitory effects on CG excretion. The chemical
      inhibition indicated that excretion of CG was contributed by the MRP family
      transporters, whereas the role of BCRP was unclear. Furthermore, short hairpin
      RNA-mediated silencing of a target transporter led to a marked reduction in the
      excretion rate of CG (38.6% for BCRP, 39.3% for MRP1, 36.4% for MRP3, and 28.7%
      for MRP4; P < 0.01). Transporter silencing also led to substantial decreases in
      the efflux clearance (44.7% for BCRP, 60.4% for MRP1, 36.7% for MRP3, and 28.7%
      for MRP4; P < 0.01). The gene silencing results suggested that BCRP, MRP1, MRP3,
      and MRP4 were significant contributors to excretion of CG. 

PMID- 25595599
TI  - Computerised physician order entry-related medication errors: analysis of
      reported errors and vulnerability testing of current systems.
AB  - IMPORTANCE: Medication computerised provider order entry (CPOE) has been shown to
      decrease errors and is being widely adopted. However, CPOE also has potential for
      introducing or contributing to errors. OBJECTIVES: The objectives of this study
      are to (a) analyse medication error reports where CPOE was reported as a
      'contributing cause' and (b) develop 'use cases' based on these reports to test
      vulnerability of current CPOE systems to these errors. METHODS: A review of
      medication errors reported to United States Pharmacopeia MEDMARX reporting system
      was made, and a taxonomy was developed for CPOE-related errors. For each error we
      evaluated what went wrong and why and identified potential prevention strategies
      and recurring error scenarios. These scenarios were then used to test
      vulnerability of leading CPOE systems, asking typical users to enter these
      erroneous orders to assess the degree to which these problematic orders could be
      entered. RESULTS: Between 2003 and 2010, 1.04 million medication errors were
      reported to MEDMARX, of which 63 040 were reported as CPOE related. A review of
      10 060 CPOE-related cases was used to derive 101 codes describing what went
      wrong, 67 codes describing reasons why errors occurred, 73 codes describing
      potential prevention strategies and 21 codes describing recurring error
      scenarios. Ability to enter these erroneous order scenarios was tested on 13 CPOE
      systems at 16 sites. Overall, 298 (79.5%) of the erroneous orders were able to be
      entered including 100 (28.0%) being 'easily' placed, another 101 (28.3%) with
      only minor workarounds and no warnings. CONCLUSIONS AND RELEVANCE: Medication
      error reports provide valuable information for understanding CPOE-related errors.
      Reports were useful for developing taxonomy and identifying recurring errors to
      which current CPOE systems are vulnerable. Enhanced monitoring, reporting and
      testing of CPOE systems are important to improve CPOE safety.

PMID- 25595600
TI  - Immunization with DISC1 protein in an animal model of ADHD influences behavior
      and excitatory amino acids in prefrontal cortex and striatum.
AB  - The Disrupted-in-schizophrenia 1 (DISC1) gene is involved in vulnerability to
      neuropsychiatric disorders. Naples high-excitability (NHE) rat model
      neuropsychiatric problems characterized by an unbalanced mesocortical dopamine
      system. Here, we assessed behavioral and neurochemical effects of immunization
      against multimeric rat DISC1 protein in adult NHE rats, an animal model of
      attention-deficit hyperactivity disorder and their Random-Bred (NRB) controls.
      Males of both lines received subcutaneous injections of vehicle (PB), adjuvant
      only (AD) or recombinant rat DISC1 protein purified from E. coli, suspended in AD
      (anti-DISC1) at age of 30, 45 and 60 postnatal days (pnd). At 75 pnd, the rats
      were exposed to a Lat maze and 2 days later to an Olton eight-arm radial maze,
      and horizontal (HA) and vertical activities (VA) were monitored. Non-selective
      (NSA) and selective spatial attention (SSA) were monitored in the Lat and in the
      Olton maze by duration of rearings and working memory, respectively. Post mortem
      neurochemistry in the prefrontal cortex (PFc), dorsal (DS) and ventral (VS)
      striatum of L-Glutamate, L-Aspartate and L-Leucine was performed. All immunized
      rats showed a clear humoral IgM (but not IgG) immune response against the
      immunogen, indicating that immunological self-tolerance to DISC1 can be overcome
      by immunization. NHE rats exhibited a higher unspecific IgM response to adjuvant,
      indicating an immunological abnormality. The sole anti-DISC1 immunization
      specific behavioral in the NHE rats was an increased horizontal activity in the
      Lat maze. Adjuvant treatment increased vertical activity in both lines, but in
      the NRB controls it increased rearing and decreased horizontal activity. Liquid
      chromatography/tandem mass spectrometry analysis of soluble or membrane-trapped
      neurotransmitters aspartate, glutamate and leucine revealed increased soluble
      aspartate levels in the ventral striatum of NRB controls after anti-DISC1
      immunization. Immune activation by adjuvant independent of simultaneous DISC1
      immunization led to other specific changes in NHE and control NRB rats. In DISC1
      immunized NHE rats, horizontal activity in Lat maze correlated with membrane
      trapped glutamate in PFc and in the NRB rats, duration of rearing in Olton maze
      correlated with membrane-trapped glutamate in PFc and aspartate in dorsal
      striatum. In addition to non-specific immune activation (by AD), the postnatal
      anti-DISC1 immune treatment led to behavioral changes related to mechanisms of
      activity and attention and had influenced amino acids and synaptic markers in
      striatum and neocortex in the adult NHE as well as control animals. 

PMID- 25595601
TI  - Investigation of the automated solid-phase synthesis of a 38mer peptide with
      difficult sequence pattern under different synthesis strategies.
AB  - Difficult peptides are a constant challenge in solid-phase peptide synthesis. In
      particular, hydroxyl amino acids such as serine can cause severe breakdowns in
      coupling yields even several amino acids after the insertion of the critical
      amino acid. This paper investigates several methods of improving synthesis yields
      of difficult peptides including the use of different resins, activators and the
      incorporation of a structure-breaking pseudoproline dipeptide building block both
      alone and in combination with each other. 

PMID- 25595602
TI  - Carvedilol improves biventricular fibrosis and function in experimental pulmonary
      hypertension.
AB  - Left ventricular (LV) function influences outcomes in right ventricular (RV)
      failure. Carvedilol reduces mortality in LV failure and improves RV function in
      experimental pulmonary arterial hypertension (PAH). However, its impact on
      ventricular-ventricular interactions and LV function in RV afterload is unknown.
      We investigated effects of carvedilol on biventricular fibrosis and function in a
      rat model of persistent PAH. Rats were randomized into three groups: Sham
      controls, PAH, and PAH + carvedilol. Severe PAH was induced by 60 mg/kg
      subcutaneous monocrotaline. In the treatment group, oral carvedilol (15
      mg/kg/day) was started 2 weeks after monocrotaline injection and continued for 3
      weeks until the terminal experiment. Echocardiography and exercise performance
      were performed at baseline and repeated at the terminal experiment with
      hemodynamic measurements. LV and RV myocardium were analyzed for hypertrophy,
      fibrosis, and molecular signaling by protein and mRNA analysis. PAH and PAH +
      carvedilol rats experienced severely elevated pulmonary arterial pressures and RV
      hypertrophy. Despite similar RV systolic pressures, carvedilol reduced
      biventricular collagen content (RV fibrosis area; 13.4 +/- 6.5 vs. 5.5 +/- 2.7 %,
      p < 0.001) and expression of transforming growth factor-beta1 (TGFbeta1) (RV
      TGFbeta1/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) ratio; 1.16 +/- 0.39
      vs. 0.57 +/- 0.22, p < 0.01) and connective tissue growth factor (CTGF) (RV
      CTGF/GAPDH ratio; 0.49 +/- 0.06 vs. 0.35 +/- 0.17, p < 0.05). RV pro-apoptotic
      caspase-8 was increased in PAH compared to controls and was significantly reduced
      in both ventricles compared to PAH animals by carvedilol. Tissue effects were
      accompanied by improved biventricular systolic and diastolic performance and
      exercise treadmill distance (36 +/- 30 vs. 80 +/- 33 m, p < 0.05). In RV pressure
      load, carvedilol improves biventricular fibrosis and function through abrogation
      of TGFbeta1-CTGF signaling. KEY MESSAGE: * RV afterload caused biventricular
      injury and dysfunction through TGFbeta1-CTGF signaling. * Carvedilol reduced
      biventricular TGFbeta1-CTGF signaling, fibrosis, and apoptosis. * Carvedilol
      improved cardiac output and biventricular function. * Improved fibrosis and
      hemodynamics occurred despite persistent RV afterload.

PMID- 25595604
TI  - A systematic review of the bimanual examination as a test for ovarian cancer.
AB  - CONTEXT: An annual bimanual pelvic examination remains widely recommended for
      healthy women, but its inclusion may discourage attendance. Our goal was to
      determine the accuracy of the pelvic examination as a screening test for ovarian
      cancer and to distinguish benign from malignant lesions. EVIDENCE ACQUISITION:
      PubMed was searched to identify studies evaluating the accuracy of the bimanual
      pelvic examination for ovarian cancer diagnosis. Data regarding study design,
      study quality, and test accuracy were abstracted. Heterogeneity was evaluated and
      meta-analysis performed where appropriate, including bivariate receiver operating
      characteristic curves. EVIDENCE SYNTHESIS: Eight studies in screening populations
      (n=36,599) and seven studies in symptomatic patients (n=782) were identified.
      Search was completed in November 2013; included studies were published between
      1988 and 2009. Screening studies were homogeneous; the summary estimates of
      sensitivity and specificity of the pelvic examination as a screening test for
      ovarian cancer were 0.44 and 0.98 (positive likelihood ratio, 24.7; negative
      likelihood ratio, 0.57). For distinguishing benign versus malignant lesions,
      there was considerable heterogeneity, with a range of sensitivity from 0.43 to
      0.93 and specificity from 0.53 to 0.91. CONCLUSIONS: The bimanual pelvic
      examination lacks accuracy as a screening test for ovarian cancer and as a way to
      distinguish benign from malignant lesions. In a typical screening population, the
      positive predictive value of an abnormal pelvic examination is only 1% (95%
      CI=0.67%, 3.0%). Its inclusion in a health maintenance examination cannot be
      justified on the basis of using it to screen for ovarian cancer.

PMID- 25595605
TI  - Changes in overall and firearm veteran suicide rates by gender, 2001-2010.

PMID- 25595603
TI  - Telemetry monitoring for non-invasive assessment of changes in core temperature
      after spinal drug administration in freely moving rats.
AB  - INTRODUCTION: There are no data available about the effects of spinally
      administered drugs on thermoregulation in freely moving animals. The first goal
      of the present study was to throw light on the consequences of intrathecally
      administered saline as a vehicle on core temperature and motor activity in
      unrestrained conditions. The second goal was to characterize the effects of
      morphine on these parameters as a widely used antinociceptive drug in spinal
      anesthesia, and reveal the potential role of the N-methyl-d-aspartate (NMDA)
      receptors in these processes. METHODS: For these purposes, male Wistar rats were
      catheterized intrathecally, and E-Mitter battery-free transponders were implanted
      intraabdominally to continuously monitor core temperature and locomotor activity.
      RESULTS: Saline induced a short-lasting hyperactivity accompanied by significant
      and prolonged hyperthermia that was blunted by systemic paracetamol
      administration. Morphine had no impact on motor activity; however, it caused high
      but equivalent degree hyperthermia in a wide dose range (1-15 MUg), suggesting
      that it reached its peak effect. In the highest applied dose (25 MUg), the NMDA
      receptor antagonist kynurenic acid blunted the saline-induced hyperthermia, and
      all doses caused higher hyperactivity compared to vehicle or morphine injections.
      In combination, kynurenic acid significantly inhibited the morphine-induced
      hyperthermia. DISCUSSION: These data suggest that this method might be a valuable
      tool for investigating the thermoregulatory and locomotor effects of different
      drugs at spinal level; however, the prolonged effects of intrathecal vehicle
      injections should also be considered. The results point out that morphine is a
      very potent hyperthermic drug that may act primarily on the efferent limb of
      thermoregulation, at least partially, via an indirect NMDA-receptor mediated
      action mechanism.

PMID- 25595606
TI  - Physical activity, walking, and quality of life in women with depressive
      symptoms.
AB  - BACKGROUND: Physical activity (PA) has a positive association with health-related
      quality of life (HRQL) in the general population. The association between PA and
      HRQL in those with poor mental health is less clear. PURPOSE: To examine the
      concurrent and prospective dose-response relationships between total PA (TPA) and
      walking only with HRQL in women aged 50-55 years with depressive symptoms in
      2001. METHODS: Participants were 1,904 women born in 1946-1951 who completed
      mailed surveys for the Australian Longitudinal Study on Women's Health in 2001,
      2004, 2007, and 2010, and reported depressive symptoms in 2001. At each time
      point, they reported their weekly minutes of walking, moderate PA, and vigorous
      PA. A summary TPA score was created that accounted for differences in energy
      expenditure among the three PA types. Mixed models were used to examine
      associations between TPA and HRQL (short form-36 [SF-36] component and subscale
      scores) and between walking and HRQL, for women who reported walking as their
      only PA. Analyses were conducted in 2013-2014. RESULTS: Concurrently, higher
      levels of TPA and walking were associated with better HRQL (p<0.05). The
      strongest associations were found for physical functioning, vitality, and social
      functioning subscales. In prospective models, associations were attenuated, yet
      compared with women doing no TPA or walking, women doing "sufficient" TPA or
      walking had significantly better HRQL over time for most SF-36 scales.
      CONCLUSIONS: This study extends previous work by demonstrating trends between
      both TPA and walking and HRQL in women reporting depressive symptoms.

PMID- 25595607
TI  - What people say # what people do.

PMID- 25595608
TI  - Emergency care facility access in rural areas within the golden hour?: Western
      Cape case study.
AB  - BACKGROUND: Road Safety is a major cause of death around the world and South
      Africa has one of the highest road fatality rates. Many measures, engineering and
      medical, are investigated. However, analysis of the accessibility of emergency
      care facilities is often overlooked. This paper aims to fill the gap between pre
      crash engineering solutions and literature on trauma injuries and emergency care
      procedures. The focus is on the role that accessibility to emergency care
      facilities in rural areas plays, given that 50% of the world's population lives
      in rural areas, which are often omitted from international research. The Western
      Cape (a rural province with low population volumes and high volume roads in South
      Africa) is analysed as an example of access to trauma care in rural areas.
      METHOD: It is internationally accepted that the time to emergency care facilities
      influences the survival chances. However, the international literature still
      debates the exact time period. In this paper, the 'Golden Hour' is used to
      analyse the accessibility of emergency care facilities in rural areas and
      establish a geographical analysis method which identifies risk areas. The
      analysis can be repeated if the international literature debates regarding the
      exact time period changes. RESULTS: A Geographical Information System (GIS) tool
      revealed that 53% of the fatalities in the rural parts of the Western Cape occur
      outside the Golden Hour. In high risk crash areas, the fatality risk is up to
      nine times higher than the province's rural average. CONCLUSIONS: People in need
      of trauma care after a road crash are most likely to survive if they receive
      definitive care timeously. At the time of the study, the rural areas in the
      Western Cape had 44 Emergency Medical Services stations and 29 medical facilities
      that can assist to provide definitive (trauma) care. Further optimisation of the
      facility locations is recommended and research has begun.More advanced
      geographical modelling is possible when improved data becomes available on the
      'Golden Hour' theory, differential times for varying injury types or travel
      speeds of ambulances. This, more advanced, modelling can reduce the road crash
      burden in rural areas around the world further.

PMID- 25595609
TI  - Health-care barriers for workers with HAVS in Ontario, Canada.
AB  - BACKGROUND: Hand-arm vibration syndrome (HAVS) becomes irreversible unless it is
      identified early and progression prevented. AIMS: To describe the health-care
      seeking behaviours of workers with HAVS and barriers to health care. METHODS: We
      invited all patients assessed for HAVS between 15 January and 27 March 2013 at a
      hospital-based occupational health clinic (OHC) in Ontario, Canada, to complete a
      questionnaire asking why and from whom they sought health care, reasons they
      waited to seek care and barriers they encountered in accessing care. We analysed
      the data using descriptive statistics. RESULTS: Forty-one (82%) patients agreed
      to participate. Thirty-seven had confirmed HAVS; 30 (84%) were Stockholm workshop
      vascular stage 2 or greater and 35 (97%) were sensorineural stage 1 or greater.
      The commonest employment sectors were construction [21 (57%)] and mining [6
      (17%)]. The main reasons for seeking treatment were pain [11 (30%)], finger
      numbness [8 (22%)] and functional limitations [5 (14%)]. The commonest initial
      point of health care was the family physician [23 (66%)]. The mean wait between
      symptom onset and seeking treatment was 3.4 years, while the mean time between
      onset and OHC assessment was 9 years. Reasons for delay in seeking care were
      ignorance of the seriousness and irreversibility of HAVS and ability to continue
      to work. Family physicians suspected HAVS in 17% of cases and recommended job
      modification in 34%. CONCLUSIONS: Workers with HAVS in Ontario delay seeking
      health care. Primary care physicians often fail to recognize HAVS. Barriers to
      health care include ignorance of HAVS and of the importance of prevention.

PMID- 25595610
TI  - Lifestyle factors associated with childhood obesity: a cross-sectional study in
      Shanghai, China.
AB  - BACKGROUND: Limited research has been conducted to investigate factors associated
      with overweight and obesity of children in China, where obesity has been
      increasing. This study investigated associations of lifestyle factors with
      overweight or obesity among Chinese primary school-aged children. METHODS: A
      cross-sectional survey was conducted with 2400 children aged 6-12 from 11 primary
      schools. Children completed a self-administered questionnaire assisted by their
      parents at home. The survey included questions on self-reported height and
      weight, screen time, physical activity, modes of travel to/from school, and
      dietary habits. Multilevel models were conducted to examine factors associated
      with overweight or obesity. RESULTS: 15.6% of children were overweight and 11.2%
      were obese; nearly 80% of children spent <=2 hrs./day either on physical
      activities or screen time. Compared with those spent >3 hrs./day on screen time,
      children who spent <=2 hrs./day or between 2-3 hrs./day were significantly less
      likely to be obese after adjusting for other variables (AOR = 0.34, 95% CI: 0.20
      0.60, P < 0.01; or AOR = 0.41, 95% CI: 0.20-0.84, P = 0.02 respectively).
      Children spent <=2 hrs./day on screen time were less likely to become overweight
      or obesity, compared with >3 hrs./day (AOR = 0.62, 95% CI: 0.38-0.99, P < 0.05).
      CONCLUSIONS: Screen time is independently associated with childhood obesity, and
      needs be focused for obesity prevention in school-aged children in China.

PMID- 25595611
TI  - Ventricular septal defect and double-chambered right ventricle in an alpaca.
AB  - A 20-month-old male alpaca was referred for evaluation of a cardiac murmur
      evident since birth. Echocardiography identified a ventricular septal defect
      (VSD) and a fibro-muscular band causing a stenosis of the right ventricular
      outflow tract. Right ventricular catheterization and selective angiography
      confirmed the diagnosis of VSD and double-chambered right ventricle with
      bidirectional shunting. 

PMID- 25595612
TI  - Permanent dual chamber epicardial pacemaker implantation in two dogs with
      complete atrioventricular block.
AB  - Between November 2013 and December 2013, two dogs with complete atrioventricular
      (AV) block had a permanent, dual chamber epicardial pacing system implanted.
      Steroid-eluting unipolar, button-type epicardial leads(a) were sutured to the
      right atrial appendage and right ventricular wall via a right thoracotomy in both
      dogs. The pacemakers were programmed in VDD mode. Permanent dual chamber
      epicardial pacemaker implantation was successful in both dogs with no intra
      operative complications. One dog had an acute onset of neurologic signs two days
      post-operatively that resolved within 24 h. Both dogs have had complete
      resolution of the clinical signs related to the bradyarrhythmia, and one dog has
      had complete resolution of chylothorax. One dog had a major lead complication
      characterized by intermittent loss of capture that resolved by increasing the
      pacemaker output. Based on the outcome of these two cases, implantation of
      permanent dual chamber epicardial pacing systems is possible in dogs providing an
      alternative to dual chamber transvenous systems.

PMID- 25595613
TI  - Speaker's hand gestures modulate speech perception through phase resetting of
      ongoing neural oscillations.
AB  - Speakers often accompany speech with spontaneous beat gestures in natural spoken
      communication. These gestures are usually aligned with lexical stress and can
      modulate the saliency of their affiliate words. Here we addressed the
      consequences of beat gestures on the neural correlates of speech perception.
      Previous studies have highlighted the role played by theta oscillations in
      temporal prediction of speech. We hypothesized that the sight of beat gestures
      may influence ongoing low-frequency neural oscillations around the onset of the
      corresponding words. Electroencephalographic (EEG) recordings were acquired while
      participants watched a continuous, naturally recorded discourse. The phase
      locking value (PLV) at word onset was calculated from the EEG from pairs of
      identical words that had been pronounced with and without a concurrent beat
      gesture in the discourse. We observed an increase in PLV in the 5-6 Hz theta
      range as well as a desynchronization in the 8-10 Hz alpha band around the onset
      of words preceded by a beat gesture. These findings suggest that beats help tune
      low-frequency oscillatory activity at relevant moments during natural speech
      perception, providing a new insight of how speech and paralinguistic information
      are integrated.

PMID- 25595614
TI  - (18)F-fluorodeoxyglucose positron emission tomography to assess response after
      radiation therapy in anaplastic thyroid cancer.
AB  - AIM: To assess the interest of (18)F-fluorodeoxyglucose positron emission
      tomography ((18)F-FDG PET/CT) to evaluate the tumor response after radiotherapy
      (RT) in anaplastic thyroid cancer (ATC) patients. METHODS AND MATERIALS: 92
      patients were treated for ATC at our institution from 1987 to 2012, out of which
      64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative
      treatment. In the multimodal treatment group, curative-intended surgery,
      chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients.
      The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes
      (N) and metastases (M) in each available (18)F-FDG PET/CT. RESULTS: The median
      follow-up was 3.2years. The 1-year actuarial overall survival (OS) was 18%
      (median: 5.2months) in the entire population and 27% (median: 7months) in the
      multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT
      chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3,
      and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19
      (30%), and 25 (39%) of (18)F-FDG PET/CT performed initially (prior to any
      treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly
      decreased in T (p<0.001), but not in N (p=0.1) and M (p=0.3) during the
      assessment period, which might be related to the local effect of RT. Comparing
      pre- and post-RT (18)F-FDG PET/CT, the T mean relative SUVmax decrease was lower
      (23+/-54%) in the 4 patients that had a local relapse (LR) as compared with
      others in the 12 others patients (62+/-33%; p=0.3). A relative SUVmax decrease
      inferior to 20% significantly predicted for LR (p=0.02). CONCLUSION: The
      prognosis of ATC patients remains dismal despite an aggressive multimodal
      treatment. Although our results were not significant, (18)F-FDG PET/CT could
      potentially serve as a surrogate marker of treatment response in ATC.

PMID- 25595615
TI  - [Imagery of treated prostate cancer].
AB  - INTRODUCTION: Diagnosis, localization of recurrence in the management of prostate
      cancer patients with increasing concentrations of tumor serum markers is crucial
      for treatment planning of the patients. The present review describes the role of
      prostate MRI and (18) Fcholine PET/computed tomography (CT) in tumor detection
      and extent, when there is a suspicion of residual or recurrent disease after
      treatment of prostate cancer. METHOD: A systematic review of the literature was
      performed by searching in the PUB MED/MEDLINE database searching for articles in
      French or English published between the last 12years. RESULTS: In patient with a
      clinical suspicion of recurrence after treatment for prostate cancer, imaging can
      be used to distinguish between local recurrence and metastatic disease. (11)C
      choline PET/CT and pelvic multiparametric MR imaging (mp MRI) are complementary
      in this indication. In this paper, the current status of imaging techniques used
      for the staging of patients with suspected locally recurrent or metastatic
      disease in patients treated for prostate cancer were reviewed. CONCLUSION: Mp MRI
      of the prostate may be valuable imaging modality for the detection and
      localization of local recurrence. C-choline PET/CT offers an advantage in
      detecting metastatic disease to lymph node and bone.

PMID- 25595616
TI  - Acute dosing and p53-deficiency promote cellular sensitivity to DNA methylating
      agents.
AB  - Risk assessment of human exposure to chemicals is crucial for understanding
      whether such agents can cause cancer. The current emphasis on avoidance of animal
      testing has placed greater importance on in vitro tests for the identification of
      genotoxicants. Selection of an appropriate in vitro dosing regime is imperative
      in determining the genotoxic effects of test chemicals. Here, the issue of dosing
      approaches was addressed by comparing acute and chronic dosing, uniquely using
      low-dose experiments. Acute 24 h exposures were compared with equivalent dosing
      every 24 h over 5-day, fractionated treatment periods. The in vitro micronucleus
      assay was used to measure clastogenicity induced by methyl methanesulfonate (MMS)
      and N-methyl-N-nitrosourea (MNU) in human lymphoblastoid cell line, TK6.
      Quantitative real-time (qRT) PCR was used to measure mRNA level induction of DNA
      repair enzymes. Lowest observed genotoxic effect levels (LOGELs) for MMS were
      obtained at 0.7 ug/ml for the acute study and 1.0 ug/ml for the chronic study.
      For acute MNU dosing, a LOGEL was observed at 0.46 ug/ml, yet genotoxicity was
      completely removed following the chronic study. Interestingly, acute MNU dosing
      demonstrated a statistically significant decrease at 0.009 ug/ml. Levels of
      selected DNA repair enzymes did not change significantly following doses tested.
      However, p53 deficiency (using the TK6-isogenic cell line, NH32) increased
      sensitivity to MMS during chronic dosing, causing this LOGEL to equate to the
      acute treatment LOGEL. In the context of the present data for 2 alkylating
      agents, chronic dosing could be a valuable in vitro supplement to acute dosing
      and could contribute to reduction of unnecessary in vivo follow-up tests.

PMID- 25595619
TI  - GeneCARD-FISH: detection of tceA and vcrA reductive dehalogenase genes in
      Dehalococcoides mccartyi by fluorescence in situ hybridization.
AB  - Due to the direct involvement in the biodegradation of chlorinated solvents,
      reductive dehalogenase genes (RDase) are considered biomarkers of the metabolic
      potential of different strains of Dehalococcoides mccartyi (Dhc). This is known
      to be the only microbe able to completely reduce toxic chlorinated solvents to
      harmless ethene. In the last years, several Molecular Biological Tools (MBTs)
      have been developed to optimize the detectability of Dhc cells and/or the RDase
      genes, with particular attention to the most important indicators of ethene
      formation, namely tceA and vcrA genes. Despite qPCR has been indicated as the MBT
      of choice, the use of CARD-FISH recently demonstrated to provide a more accurate
      quantification of Dhc cells in a wide concentration range, overcoming the
      drawbacks of loosing nucleic acids during the preparation of the sample
      associated with qPCR. CARD-FISH assays usually target 16S rRNA and up to date no
      protocol able to discriminate different Dhc strains by detecting RDase genes has
      been developed. This study reports the first evidence of in situ detection of
      tceA and vcrA genes into Dhc cells by applying a new procedure named geneCARD
      FISH. Dhc strains carrying tceA and vcrA genes were identified and quantified in
      a PCE-to-ethene dechlorinating microbial enrichment and overall they represented
      58.63%+/-2.45% and 40.46%+/-1.86% of the total Dhc cells, respectively. These
      values were markedly higher than those obtained by qPCR, which strongly
      underestimated the actual concentration of vcrA gene (0.08%+/-0.01% of Dhc 16S
      rRNA gene copies). The assay was successfully applied also for the analysis of
      environmental samples and remarkably strengthens the biomonitoring activities at
      field scale by providing the specific in situ discrimination of Dhc cells
      carrying the key-RDase genes. 

PMID- 25595618
TI  - Cross-border collaboration between China and Myanmar for emergency response to
      imported vaccine derived poliovirus case.
AB  - BACKGROUND: This report describes emergency response following an imported
      vaccine derived poliovirus (VDPV) case from Myanmar to Yunnan Province, China and
      the cross-border collaboration between China and Myanmar. Immediately after
      confirmation of the VDPV case, China disseminated related information to Myanmar
      with the assistance of the World Health Organization. METHODS: A series of
      epidemiological investigations were conducted, both in China and Myanmar,
      including retrospective searches of acute flaccid paralysis (AFP) cases, oral
      poliovirus vaccine (OPV) coverage assessment, and investigation of contacts and
      healthy children. RESULTS: All children <2 years of age had not been vaccinated
      in the village where the VDPV case had lived in the past 2 years. Moreover, most
      areas were not covered for routine immunization in this township due to vaccine
      shortages and lack of operational funds for the past 2 years. CONCLUSIONS: Cross
      border collaboration may have prevented a potential outbreak of VDPV in Myanmar.
      It is necessary to reinforce cross-border collaboration with neighboring
      countries in order to maximize the leverage of limited resources.

PMID- 25595620
TI  - Decreased diffusion capacity on lung function testing in asymptomatic patients
      with systemic lupus erythematosus does not predict future lung disease.
AB  - BACKGROUND: In a previous study performed 9 +/- 3.6 years ago, 74 asymptomatic
      patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome
      (APS) underwent lung function testing. A significantly low diffusion capacity
      (DLCO) ranging from 45% to 70% was recorded in 28 of the 74 (37.8%) patients who
      were all free of respiratory symptoms. AIM: The aim of this report is to assess
      the clinical importance and the predictive value of a low DLCO in asymptomatic
      patients with SLE or APS. METHODS: Asymptomatic patients with SLE and/or APS who
      were found to have a low DLCO in the previous study were contacted. Of the 28
      patients, 15 were recruited and reevaluated in the current study (SLE with APS (n
      = 7), SLE without APS (n = 7); primary APS (n = 1)). A full history, physical
      examination, nail bed capillaroscopy, current laboratory tests and full lung
      function tests including DLCO were performed. RESULTS: During a surveillance
      period of 9 +/- 3.6 years, none of the patients developed lung disease. Diffusion
      capacity corrected for alveolar volume (DLCO/VA) improved in the study group
      during this period from 60.4% +/- 7.0 to 76.1% +/- 11.2 (p < 0.0001). Lung
      function tests including total lung capacity (TLC) and forced expiratory volume
      in one second (FEV1) remained within normal limits. Capillaroscopy studies did
      not reveal changes compatible with scleroderma in any of the patients.
      CONCLUSION: Low DLCO findings on lung function testing does not have a positive
      predictive value for the development of future lung disease in patients with SLE,
      with or without APS, who are free of respiratory symptoms. Our results suggest
      that a finding of low DLCO in asymptomatic patients with SLE, with or without
      APS, does not necessarily require further evaluation and imaging and may improve
      spontaneously over time. Further studies in a larger group of patients are needed
      to validate these findings.

PMID- 25595622
TI  - Enhancing capacitive deionization performance of electrospun activated carbon
      nanofibers by coupling with carbon nanotubes.
AB  - Capacitive deionization (CDI) is an alternative, effective and environmentally
      friendly technology for desalination of brackish water. The performance of the
      CDI device is highly determined by the electrode materials. In this paper, a
      composite of carbon nanotubes (CNTs) embedded in activated carbon nanofiber (ACF)
      was prepared by a direct co-electrospinning way and subsequent CO2 activation.
      The introduction of CNTs can greatly improve the conductivity while the CO2
      mediated activation can render the final product with high porosity. As such, the
      hybrid structure can provide an excellent storage space and pathways for ion
      adsorption and conduction. When evaluated as electrode materials for CDI, the as
      prepared CNT/ACF composites with higher electrical conductivity and mesopore
      ratios exhibited higher electrosorption capacity and good regeneration
      performance in comparison with the pure ACF. 

PMID- 25595621
TI  - Systemic lupus erythematosus is not a risk factor for poor outcomes after total
      hip and total knee arthroplasty.
AB  - OBJECTIVES: Historically, arthroplasty in systemic lupus erythematosus (SLE)
      patients has been less successful than for patients with osteoarthritis (OA). It
      is not known if SLE remains an independent risk factor for poor arthroplasty
      outcomes or if other factors, such as avascular necrosis (AVN), continue to play
      a role. METHODS: A case-control study using data from a single-institution
      arthroplasty registry compared SLE total hip arthroplasty (THA) and total knee
      arthroplasty (TKA) with OA controls matched by age, gender and presence of AVN.
      Baseline, two-year administrative and self-report data, and diagnosis leading to
      arthroplasty were evaluated. RESULTS: A total of 54 primary SLE THA and 45
      primary SLE TKA were identified from May 2007 through June 2011. AVN was present
      in 32% of SLE THA and no TKA. SLE THA had worse preoperative WOMAC pain (42.5 vs.
      52.7; p = 0.01) and function (38.8 vs. 48.0; p = 0.05) compared with OA. However,
      at two years there was no difference in WOMAC pain (91.1 vs. 92.1; p = 0.77) or
      WOMAC function (86.4 vs. 90.8; p = 0.28). SLE TKA were similar to OA in both
      preoperative pain (42.6 vs. 48.4; p = 0.14) and function (42.1 vs. 46.8; p =
      0.30) and two-year pain (85.7 vs. 88.6; p = 0.50) and function (83.7 vs. 85.1; p
      = 0.23). Compared to OA, SLE THA and TKA patients had more renal failure (14% vs.
      1%; p = 0.007) and hypertension (52% vs. 29%; p = 0.009). In a multivariate
      linear regression, SLE was not predictive of either poor pain or poor function.
      CONCLUSIONS: While SLE patients have more comorbidities than OA, and SLE THA have
      worse preoperative pain and function compared with OA controls, SLE was not an
      independent risk factor for poor short-term pain or function after either hip or
      knee arthroplasty.

PMID- 25595623
TI  - Charge regulation at semiconductor-electrolyte interfaces.
AB  - The interface between a semiconductor material and an electrolyte solution has
      interesting and complex electrostatic properties. Its behavior will depend on the
      density of mobile charge carriers that are present in both phases as well as on
      the surface chemistry at the interface through local charge regulation. The
      latter is driven by chemical equilibria involving the immobile surface groups and
      the potential determining ions in the electrolyte solution. All these lead to an
      electrostatic potential distribution that propagate such that the electrolyte and
      the semiconductor are dependent on each other. Hence, any variation in the charge
      density in one phase will lead to a response in the other. This has significant
      implications on the physical properties of single semiconductor-electrolyte
      interfaces and on the electrostatic interactions between semiconductor particles
      suspended in electrolyte solutions. The present paper expands on our previous
      publication (Fleharty et al., 2014) and offers new results on the electrostatics
      of single semiconductor interfaces as well as on the interaction of charged
      semiconductor colloids suspended in electrolyte solution. 

PMID- 25595624
TI  - Foam drainage. Possible influence of a non-newtonian surface shear viscosity.
AB  - We describe forced drainage experiments of foams made with model surfactant
      solutions with different surface rheology. We analyze the origin of two distinct
      drainage transitions reported in the literature, between regimes where the bubble
      surfaces are mobile or rigid. We propose that both transitions are related to the
      surface shear viscosity and to its shear thinning behavior. Shear thinning could
      also account for the huge discrepancies between measurements reported in the
      literature. The role of surface tension gradients, i.e. Marangoni effect, could
      not possibly explain the behavior observed with the different solutions. 

PMID- 25595625
TI  - Collective excitations in 2D hard-disc fluid.
AB  - Collective dynamics of a two-dimensional (2D) hard-disc fluid was studied by
      molecular dynamics simulations in the range of packing fractions that covers
      states up to the freezing. Some striking features concerning collective
      excitations in this system were observed. In particular, the short-wavelength
      shear waves while being absent at low packing fractions were observed in the
      range of high packing fractions, just before the freezing transition in a 2D hard
      disc fluid. In contrast, the so-called "positive sound dispersion" typically
      observed in dense Lennard-Jones-like fluids, was not detected for the 2D hard
      disc fluid. The ratio of specific heats in the 2D hard-disc fluid shows a
      monotonic increase with density approaching the freezing, resembling in this way
      the similar behavior in the vicinity of the Widom line in the case of
      supercritical fluids. 

PMID- 25595626
TI  - "Non-equilibrium" block copolymer micelles with glassy cores: a predictive
      approach based on theory of equilibrium micelles.
AB  - Micelles generated in water from most amphiphilic block copolymers are widely
      recognized to be non-equilibrium structures. Typically, the micelles are prepared
      by a kinetic process, first allowing molecular scale dissolution of the block
      copolymer in a common solvent that likes both the blocks and then gradually
      replacing the common solvent by water to promote the hydrophobic blocks to
      aggregate and create the micelles. The non-equilibrium nature of the micelle
      originates from the fact that dynamic exchange between the block copolymer
      molecules in the micelle and the singly dispersed block copolymer molecules in
      water is suppressed, because of the glassy nature of the core forming polymer
      block and/or its very large hydrophobicity. Although most amphiphilic block
      copolymers generate such non-equilibrium micelles, no theoretical approach to a
      priori predict the micelle characteristics currently exists. In this work, we
      propose a predictive approach for non-equilibrium micelles with glassy cores by
      applying the equilibrium theory of micelles in two steps. In the first, we
      calculate the properties of micelles formed in the mixed solvent while true
      equilibrium prevails, until the micelle core becomes glassy. In the second step,
      we freeze the micelle aggregation number at this glassy state and calculate the
      corona dimension from the equilibrium theory of micelles. The condition when the
      micelle core becomes glassy is independently determined from a statistical
      thermodynamic treatment of diluent effect on polymer glass transition
      temperature. The predictions based on this "non-equilibrium" model compare
      reasonably well with experimental data for polystyrene-polyethylene oxide diblock
      copolymer, which is the most extensively studied system in the literature. In
      contrast, the application of the equilibrium model to describe such a system
      significantly overpredicts the micelle core and corona dimensions and the
      aggregation number. The non-equilibrium model suggests ways to obtain different
      micelle sizes for the same block copolymer, by the choices we can make of the
      common solvent and the mode of solvent substitution. 

PMID- 25595628
TI  - [Blindness and visual rehabilitation].
AB  - Blindness and visual impairment are a major public health problem all over the
      world and in all societies. A large amount of basic science and clinical research
      aims to rehabilitate patients and help them become more independent. Various
      methods are explored from cell and molecular therapy to prosthetic interfaces. We
      review the various treatment alternatives, describing their results and their
      limitations. 

PMID- 25595629
TI  - [Iris leiomyoma: a benign tumor in an atypical location].

PMID- 25595627
TI  - Safety and effectiveness of compassionate use of LARIAT(r) device for epicardial
      ligation of anatomically complex left atrial appendages.
AB  - BACKGROUND: Percutaneous left atrial appendage (LAA) ligation using an epicardial
      suture system (LARIAT(r), SentreHEART, Palo Alto, CA) has been used in patients
      with nonvalvular atrial fibrillation (AF) and contraindication to oral
      anticoagulation. However, complex LAA anatomy may preclude its use. We report the
      safety and effectiveness of compassionate use of first-generation LARIAT(r)
      device for epicardial ligation of large, complex left atrial appendages. METHODS:
      Between January 2010 and March 2013, 93 patients with AF, high CHADS2 score, and
      contraindication(s) for oral anticoagulation therapy were evaluated for LAA
      ligation. Complex anatomy detected by 3D cardiac computed tomography CT
      angiography led to preclusion of 25 patients (27%). Of these, nine patients who
      opted for epicardial LAA ligation on compassionate grounds were studied. RESULTS:
      Mean age was 68.1 +/- 8.2 years, four females, all with large LAA width (>40 mm,
      45-58 mm) and additional anatomic complexities such as bilobed (two), long C
      shaped-like (two), goose neck-like (one), multilobed cauliflower-like (two),
      cactus-like (one), and chicken wing-like (one) LAA. LAA ligation with LARIAT(r)
      was successfully performed with surgical standby in all patients. Seven patients
      (78%) were safely treated percutaneously and only two patients required minimally
      invasive thoracotomy (one due to inability to release the epicardial snare from
      long C-shaped LAA and other due to preexisting adhesions precluding pericardial
      entry). There were no major complications. Repeat trans-esophageal
      echocardiography at 3 months showed no remnant flow and none had stroke off
      Coumadin at 19.3 +/- 8.2 months of follow-up. CONCLUSIONS: Despite a high
      preclusion rate, percutaneous LAA ligation may be safely and effectively
      performed on compassionate grounds using the first-generation LARIAT(r) device
      with surgical standby in patients with large and complex LAA.

PMID- 25595631
TI  - [Secondary opacification of a hydrophilic acrylic multifocal intraocular lens
      with a hydrophobic surface].

PMID- 25595630
TI  - [Atheromatous retinal emboli: complications and SD-OCT characteristics].

PMID- 25595632
TI  - Prognostic factors for survival in patients with Ewing's sarcoma using the
      surveillance, epidemiology, and end results (SEER) program database.
AB  - BACKGROUND: The current study aims to determine cause-specific survival in
      patients with Ewing's sarcoma while reporting clinical risk factors for survival.
      METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program database
      was used to identify patients with osseous Ewing's sarcoma from 1991 to 2010.
      Patient, tumor, and socioeconomic variables were analyzed to determine prognostic
      factors for survival. RESULTS: There were 1163 patients with Ewing's sarcoma
      identified in the SEER Program database. The 10-year cause-specific survival for
      patients with non-metastatic disease at diagnosis was 66.8% and 28.1% for
      patients with metastatic disease. Black patients demonstrated reduced survival at
      10 years with an increased frequency of metastatic disease at diagnosis as
      compared to patients of other race, while Hispanic patients more frequently
      presented with tumor size>10cm. Univariate analysis revealed that metastatic
      disease at presentation, tumor size>10cm, axial tumor location, patient age>=20
      years, black race, and male sex were associated with decreased cause-specific
      survival at 10 years. Metastatic disease at presentation, axial tumor location,
      tumor size>10cm, and age>=20 years remained significant in the multivariate
      analysis. CONCLUSIONS: Patients with Ewing's sarcoma have decreased cause
      specific survival at 10 years when metastatic at presentation, axial tumor
      location, tumor size>10cm, and patient age>=20 years.

PMID- 25595633
TI  - Intrathoracic peripheral nerve sheath tumors-a clinicopathological study of 75
      cases.
AB  - Although peripheral nerve sheath tumors (PNSTs) are common in the posterior
      mediastinum, they are rare in other mediastinal compartments and in the
      pleuropulmonary parenchyma. We sought to characterize the clinicopathological
      features of PNSTs occurring in the lung, pleura, and mediastinum. Diagnoses were
      confirmed by slide review. Study cases include 21 benign pleuropulmonary PNSTs,
      49 benign mediastinal PNSTs, and 5 malignant PNSTs. Benign pleuropulmonary tumors
      comprised 13 schwannomas, 6 neurofibromas, 1 perineurioma, and 1 ganglioneuroma.
      Six lesions were endobronchial (3 neurofibromas, 1 schwannoma, 1 perineurioma, 1
      ganglioneuroma), whereas the remaining schwannomas and neurofibromas formed
      parenchymal masses (usually pleural based). Benign mediastinal PNSTs (46
      posterior, 2 middle, and 1 anterior) were all schwannomas and showed a female
      predominance. None of the patients with benign PNSTs experienced recurrence. Of
      the 5 malignant PNSTs, 4 were pleuropulmonary (3 pleural based) and 1 occurred in
      the anterior mediastinum. Two of the 5 patients had a history of
      neurofibromatosis type 1 (aged 27 and 45 years). At last follow-up, 3 of the 5
      patients had died of disease, 1 was alive with disease, and 1 was alive with no
      evidence of disease (41 months). Although rare, a wide histologic range of PNSTs
      occur in the lung. Although neurofibroma, perineurioma, and ganglioneuroma were
      observed as endobronchial lesions, most pulmonary schwannomas were pleural-based
      masses. Mediastinal PNSTs are dominated by posterior mediastinal schwannomas,
      although schwannomas rarely occur in the other mediastinal compartments as well.
      Malignant PNSTs are very rare in the thorax, where they show aggressive behavior.

PMID- 25595634
TI  - Cryopreservation of boar sperm comparing different cryoprotectants associated in
      media based on powdered coconut water, lactose and trehalose.
AB  - In swine spermatozoa, the damage caused by cryopreservation is more severe than
      other species, provoking reduced potential for fertilization. Adjustments in the
      freezing extender composition may be an important alternative to increase its
      efficiency. The objective of this study was to test the efficiency of different
      cryoprotectant solutions during cryopreservation of swine semen with a controlled
      cooling curve. Three cryoprotectant solutions (5% dimethylformamide, 3% glycerol
      and the combination of these two cryoprotectants) were used in association with
      three base media (powdered coconut water, lactose and trehalose), constituting
      nine different treatments. The semen was frozen using a controlled-rate freezer
      (TK-3000). After thawing, semen was evaluated for total sperm motility, vigor,
      morphology, plasma membrane integrity and acrosome integrity. Cryopreservation
      with the controlled curve using an automated system showed satisfactory results,
      guaranteeing practicality and repeatability for the process of freezing swine
      sperm. With this curve, the solutions of lactose, trehalose and powdered coconut
      water associated with glycerol, as well as the solution of coconut water
      containing dimethylformamide, presented higher quality of sperm compared to the
      other solutions. Powdered coconut water associated with dimethylformamide appears
      as a new solution for swine sperm cryopreservation. The freezing controlled curve
      used in this study allowed standardization of the cryopreservation technique. 

PMID- 25595635
TI  - Cryoplasty versus angioplasty in the treatment of arterial restenosis in an
      experimental model of atherosclerosis in rabbits.
AB  - Cryoplasty may reduce the incidence of post-angioplasty restenosis in peripheral
      atherosclerotic arteries. Our study is looking to investigate the mid-term
      effects (4 weeks) of an FDA-approved cryoplasty catheter (PolarCath((r)), Boston
      Scientific) compared to a conventional angioplasty catheter using a
      hypercholesterolemic rabbit model of arterial restenosis based on diet plus
      vessel injury. Thirty-six normolipidemic, 3-month old male New Zealand White
      rabbits were used. Balloon angioplasty was performed on left external iliac
      arteries on day 1. Animals were fed with a hypercholesterolemic diet for 60 days.
      On day 120, three groups of animals were established: conventional PTA
      (percutaneous transluminal angioplasty) was applied on the PTA group; the CRY
      group was treated with the PolarCath((r)) cryoplasty system and no treatment was
      given to a control (CTR) group. A broad variety of atheromatous lesions were
      observed 30 days after treatment, presenting significant differences between
      groups. Most of the complicated lesions were found in the CRY group, while
      advanced and early lesions were more often appreciated in the CTR and PTA groups,
      respectively. The histomorphometric evaluation of the arteries showed significant
      differences between the CRY group and the other two groups, with the highest
      percentage of IEM (internal elastic membrane) injury, vascular stenosis and ratio
      intima/media being registered on animals treated with cryoplasty. Intravascular
      cryotherapy induces complicated lesions in arterial walls 30 days after treatment
      in a hypercholesterolemic rabbit model based on diet plus vessel injury.
      Cryoplasty leads to the production of severe fibrosis and mineralisation and
      stenosis compared to a conventional angioplasty.

PMID- 25595636
TI  - Modulation of antifreeze activity and the effect upon post-thaw HepG2 cell
      viability after cryopreservation.
AB  - Most antifreeze proteins (AFPs) exhibit two types of "antifreeze activity" -
      thermal hysteresis (TH) and ice recrystallization inhibition (IRI) activity. The
      mechanism of TH activity has been studied in depth and is the result of an
      adsorption of AFPs to the surface of ice with an ice-binding face (IBF). In
      contrast, the mechanism of ice recrystallization and its inhibition is
      considerably less understood. In this paper, we examine several different
      antifreeze proteins, glycoproteins and mutants of the Lolium perenne AFP (LpAFP)
      to understand how IRI activity is modulated independently of TH activity. This
      study also examines the ability of the various AF(G)Ps to protect HepG2 cells
      from cryoinjury. Post-thaw cell viabilities are correlated to TH, IRI activity as
      well as dynamic ice shaping ability and single ice crystal growth progressions.
      While these results demonstrate that AF(G)Ps are ineffective as cryoprotectants,
      they emphasize how ice crystal habit and most importantly, ice growth progression
      affect HepG2 cell survival during cryopreservation. 

PMID- 25595637
TI  - Emergency Ebola response: a new approach to the rapid design and development of
      vaccines against emerging diseases.
AB  - The epidemic of Ebola virus disease has spread at an alarming rate despite
      containment efforts. As a result, unprecedented large-scale international
      response efforts have been made in an attempt to gain control of the outbreak and
      reduce transmission. Several international consortia have been formed in a
      remarkable worldwide collaborative effort to expedite trials of two candidate
      Ebola virus vaccines: cAd3-EBOZ and rVSV-EBOV. In parallel, both vaccines are
      being manufactured in large amounts to enable future rapid deployment for
      management of the crisis. 

PMID- 25595638
TI  - Effects of cooking methods on phenolic compounds in xoconostle (Opuntia
      joconostle).
AB  - Xoconostle, the acidic cactus pear fruit of Opuntia joconostle of the Cactaceae
      family, is the source of several phytochemicals, such as betalain pigments and
      numerous phenolic compounds. The aim of the present study was to analyze the
      effect of four cooking procedures (i.e., boiling, grilling, steaming and
      microwaving) on the total phenolic content (TPC) and antioxidant activity
      (measured by ABTS, DPPH, reducing power, and BCBA) of xoconostle. In addition,
      HPLC-DAD analyses were performed to identify and quantify individual phenolic
      compounds. After microwaving and steaming xoconostle, the TPC remained the same
      that in fresh samples, whereas both grilling and boiling produced a significant,
      20% reduction (p <= 0.05). Total flavonoids remained unchanged in boiled and
      grilled xoconostle, but steaming and microwaving increased the flavonoid content
      by 13 and 20%, respectively. Steaming and microwaving did not produce significant
      changes in the antioxidant activity of xoconostle, whereas boiling and grilling
      result in significant decreases. The phenolic acids identified in xoconostle
      fruits were gallic, vanillic, 4-hydroxybenzoic, syringic, ferulic and
      protocatechuic acids; the flavonoids identified were epicatechin, catechin,
      rutin, quercitrin, quercetin and kaempferol. Based on the results, steaming and
      microwaving are the most suitable methods for retaining the highest level of
      phenolic compounds and flavonoids in xoconostle.

PMID- 25595639
TI  - Evaluation of anthropometric measurements at birth in predicting birthweight less
      than 2000 g in African and Asian newborns: a meta-analysis.
AB  - BACKGROUND: Particularly in developing countries, lower birthweight may be
      associated with higher neonatal mortality, and deliveries frequently take place
      at home where scales are not always available. Therefore, surrogate measurements
      for birthweight are necessary as a primary screening measure. The aim of this
      study was to determine whether newborn chest and arm circumferences can predict
      birthweight less than 2000 g. METHODS: The selection criteria were studies
      published in English that could provide all the true- and false-positive and true
      and false-negative results with regard to the prediction of birthweight less
      than 2000 g by other anthropometric measurements among apparently healthy
      neonates. Ten bibliographic databases (e.g., PubMed) were searched and a
      bivariate meta-analysis was conducted with hierarchical summary receiver
      operating characteristic (ROC) curves. A total of 36,987 participants in 24
      studies for chest circumference and 16,164 participants in 15 studies for arm
      circumference were included. The study regions were limited to Africa and Asia.
      RESULTS: For chest and arm circumferences (24 and 15 studies, respectively),
      pooled sensitivity (0.94 and 0.89, respectively) and specificity (0.94 and 0.96,
      respectively), and diagnostic odds ratios (263 and 174, respectively) were
      sufficiently high to allow good predictions. The diagnostic odds ratio for chest
      circumference was significantly higher than for arm circumference (P<0.001). The
      generalizability of the findings is to some extent guaranteed. CONCLUSION:
      Newborn chest and arm circumferences may be useful predictors of birthweight less
      than 2000 g, with chest circumference possibly better.

PMID- 25595640
TI  - Topographic deformation patterns of knee cartilage after exercises with high knee
      flexion: an in vivo 3D MRI study using voxel-based analysis at 3T.
AB  - OBJECTIVES: To implement a novel voxel-based technique to identify statistically
      significant local cartilage deformation and analyze in-vivo topographic knee
      cartilage deformation patterns using a voxel-based thickness map approach for
      high-flexion postures. METHODS: Sagittal 3T 3D-T1w-FLASH-WE-sequences of 10
      healthy knees were acquired before and immediately after loading
      (kneeling/squatting/heel sitting/knee bends). After cartilage segmentation, 3D
      reconstruction and 3D-registration, colour-coded deformation maps were generated
      by voxel-based subtraction of loaded from unloaded datasets to visualize
      cartilage thickness changes in all knee compartments. RESULTS: Compression areas
      were found bifocal at the peripheral medial/caudolateral patella, both posterior
      femoral condyles and both anterior/central tibiae. Local cartilage thickening
      were found adjacent to the compression areas. Significant local strain ranged
      from +13 to -15 %. Changes were most pronounced after squatting, least after knee
      bends. Shape and location of deformation areas varied slightly with the loading
      paradigm, but followed a similar pattern consistent between different
      individuals. CONCLUSIONS: Voxel-based deformation maps identify individual in
      vivo load-specific and posture-associated strain distribution in the articular
      cartilage. The data facilitate understanding individual knee loading properties
      and contribute to improve biomechanical 3 models. They lay a base to investigate
      the relationship between cartilage degeneration patterns in common osteoarthritis
      and areas at risk of cartilage wear due to mechanical loading in work-related
      activities. KEY POINTS: * 3D MRI helps differentiate true knee-cartilage
      deformation from random measurement error * 3D MRI maps depict in vivo
      topographic distribution of cartilage deformation after loading * 3D MRI maps
      depict in vivo intensity of cartilage deformation after loading * Locating
      cartilage contact areas might aid differentiating common and work-related
      osteoarthritis.

PMID- 25595641
TI  - The effect of renal denervation on kidney oxygenation as determined by BOLD MRI
      in patients with hypertension.
AB  - OBJECTIVES: Renal denervation (RDN) is a promising therapy for resistant
      hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN
      can potentially increase renal oxygenation. Blood oxygen level-dependent MRI
      (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans.
      The aim of the current study was to investigate the effect of RDN on renal
      oxygenation as determined by BOLD-MRI. METHODS: Patients with resistant
      hypertension or the inability to follow a stable drug regimen due to unacceptable
      side effects were included. BOLD-MRI was performed before and 12 months after
      RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI
      systems. RESULTS: Fifty-four patients were included, 46 patients (23 men, mean
      age 57 years) completed the study. Mean 24-h BP changed from 163(+/-20)/98(+/-14)
      mmHg to 154(+/-22)/92(+/-13) mmHg (p = 0.001 and p < 0.001). eGFR did not change
      after RDN [77(+/-18) vs. 79(+/-20) mL/min/1.73 m(2); p = 0.13]. RDN did not
      affect renal oxygenation [1.5 T: cortical R2*: 12.5(+/-0.9) vs. 12.5(+/-0.9), p =
      0.94; medullary R2*: 19.6(+/-1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*:
      18.1(+/-0.8) vs. 17.8(+/-1.2), p = 0.47; medullary R2*: 27.4(+/-1.9) vs. 26.7(+/
      1.8), p = 0.19]. CONCLUSION: The current study shows that RDN does not lead to
      changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. KEY
      POINTS: * Renal denervation significantly decreased ambulatory blood pressure. *
      Renal denervation did not change renal oxygenation as determined by BOLD-MRI. *
      Absence of a change in renal oxygenation might be explained by autoregulation.

PMID- 25595642
TI  - Bleomycin induced epithelial-mesenchymal transition (EMT) in pleural mesothelial
      cells.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease
      characterized by the development of subpleural foci of myofibroblasts that
      contribute to the exuberant fibrosis. Recent studies revealed that pleural
      mesothelial cells (PMCs) undergo epithelial-mesenchymal transition (EMT) and play
      a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis
      exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not
      known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were
      cultured and treated with bleomycin. The protein levels of collagen-I,
      mesenchymal phenotypic markers (vimentin and alpha-smooth muscle actin), and
      epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by
      Western blot. PMC migration was evaluated using wound-healing assay of culture
      PMCs in vitro, and in vivo by monitoring the localization of PMC marker,
      calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results
      showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin
      induced significant increases in mesenchymal phenotypic markers and decreases in
      epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in
      vivo. Moreover, TGF-beta1-Smad2/3 signaling pathway involved in the EMT of PMC
      was demonstrated. Taken together, our results indicate that bleomycin induces
      characteristic changes of EMT in PMC and the latter contributes to subpleural
      fibrosis. 

PMID- 25595643
TI  - The midgut cadherin-like gene is not associated with resistance to Bacillus
      thuringiensis toxin Cry1Ac in Plutella xylostella (L.).
AB  - The Gram-positive bacterium Bacillus thuringiensis (Bt) produces Cry toxins that
      have been used to control important agricultural pests. Evolution of resistance
      in target pests threatens the effectiveness of these toxins when used either in
      sprayed biopesticides or in Bt transgenic crops. Although alterations of the
      midgut cadherin-like receptor can lead to Bt Cry toxin resistance in many
      insects, whether the cadherin gene is involved in Cry1Ac resistance of Plutella
      xylostella (L.) remains unclear. Here, we present experimental evidence that
      resistance to Cry1Ac or Bt var. kurstaki (Btk) in P. xylostella is not due to
      alterations of the cadherin gene. The bona fide P. xylostella cadherin cDNA
      sequence was cloned and analyzed, and comparisons of the cadherin cDNA sequence
      among susceptible and resistant P. xylostella strains confirmed that Cry1Ac
      resistance was independent of mutations in this gene. In addition, real-time
      quantitative PCR (qPCR) indicated that cadherin transcript levels did not
      significantly differ among susceptible and resistant P. xylostella strains. RNA
      interference (RNAi)-mediated suppression of cadherin gene expression did not
      affect larval susceptibility to Cry1Ac toxin. Furthermore, genetic linkage assays
      using four cadherin gDNA allelic biomarkers confirmed that the cadherin gene is
      not linked to resistance against Cry1Ac in P. xylostella. Taken together, our
      findings demonstrate that Cry1Ac resistance of P. xylostella is independent of
      the cadherin gene. 

PMID- 25595644
TI  - The impact of vitamin D on fetal and neonatal lung maturation. A systematic
      review.
AB  - Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) are
      major complications to preterm birth. Hypovitaminosis D is prevalent in
      pregnancy. We systematically reviewed the evidence of the impact of vitamin D on
      lung development, surfactant synthesis, RDS, and BPD searching PubMed, Embase,
      and Cochrane databases with the terms vitamin D AND (surfactant OR lung
      maturation OR lung development OR respiratory distress syndrome OR fetal lung OR
      prematurity OR bronchopulmonary dysplasia). Three human studies, ten animal
      studies, two laboratory studies, and one combined animal and laboratory study
      were included. Human evidence was sparse, allowing no conclusions. BPD was not
      associated with vitamin D receptor polymorphism in a fully adjusted analysis.
      Animal and laboratory studies showed substantial positive effects of vitamin D on
      the alveolar type II cell, fibroblast proliferation, surfactant synthesis, and
      alveolarization. These data support the hypothesis of hypovitaminosis D as a
      frequent, modifiable risk factor of RDS and BPD, which should be tested in
      randomized controlled trials on pregnant women, those with threatening preterm
      delivery, or in the preterm neonates. Future experimental and human studies
      should aim to identify optimal time windows, vitamin D doses, and cut-off levels
      for 25-hydroxyvitamin D in interventions against RDS, BPD, and later adverse
      respiratory outcomes.

PMID- 25595645
TI  - Inspiratory resistive breathing induces MMP-9 and MMP-12 expression in the lung.
AB  - Inspiratory resistive breathing (IRB) is characterized by large negative
      intrathoracic pressures and was shown to induce pulmonary inflammation in
      previously healthy rats. Matrix metalloproteinases (MMP)-9 and -12 are induced by
      inflammation and mechanical stress in the lung. We hypothesized that IRB induces
      MMP-9 and -12 in the lung. Anesthetized, tracheostomized rats breathed
      spontaneously through a two-way valve, connected to an inspiratory resistance,
      with the tidal inspiratory tracheal pressure set at 50% of the maximum. Quietly
      breathing animals served as controls. After 3 and 6 h of IRB, respiratory
      mechanics were measured, bronchoalveolar lavage (BAL) was performed, lung injury
      score was estimated, and lung MMP-9 was estimated by zymography and ELISA. MMP-9
      and MMP-12 immunohistochemistry was performed. Isolated normal alveolar
      macrophages were incubated with BAL from rats that underwent IRB. After 18 h, MMP
      9 and -12 levels were measured in supernatants, and immunocytochemistry was
      performed. Macrophages were treated with IL-1beta, IL-6, or TNF-alpha, and MMP-9
      in supernatants was measured. After 6 h of IRB, leukocytes in BAL increased, and
      IL-1beta and IL-6 levels were elevated. Elasticity and injury score were
      increased after 3 and 6 h of IRB. Lung MMP-9 levels increased after 6 h of IRB.
      MMP-9 and MMP-12 were detected in alveolar macrophages and epithelial
      (bronchial/alveolar) cells after 3 and 6 h of IRB. MMP-9 and MMP-12 were found in
      supernatants after treatment with 6 h of IRB BAL. Cytosolic immunostaining was
      detected after treatment with 3 and 6 h of IRB BAL. All cytokines induced MMP-9
      in culture supernatants. In conclusion, IRB induces MMP-9 and -12 in the lung of
      previously healthy rats.

PMID- 25595646
TI  - Enhanced inflammation in aged mice following infection with Streptococcus
      pneumoniae is associated with decreased IL-10 and augmented chemokine production.
AB  - Streptococcus pneumoniae is the most common cause of severe pneumonia in the
      elderly. However, the impact of aging on the innate inflammatory response to
      pneumococci is poorly defined. We compared the innate immune response in old vs.
      young adult mice following infection with S. pneumoniae. The accumulation of
      neutrophils recovered from bronchoalveolar lavage fluid and lung homogenates was
      increased in aged compared with young adult mice, although bacterial outgrowth
      was similar in both age groups, as were markers of microvascular leak. Aged mice
      had similar levels of IL-1beta, TNF, IFN-gamma, IL-17, and granulocyte colony
      stimulating factor following S. pneumoniae infection, compared with young mice,
      but increased levels of the chemokines CXCL9, CXCL12, CCL3, CCL4, CCL5, CCL11,
      and CCL17. Moreover, levels of IL-10 were significantly lower in aged animals.
      Neutralization of IL-10 in infected young mice was associated with increased
      neutrophil recruitment but no decrease in bacterial outgrowth. Furthermore, IL-10
      neutralization resulted in increased levels of CCL3, CCL5, and CXCL10. We
      conclude that aging is associated with enhanced inflammatory responses following
      S. pneumoniae infection as a result of a compromised immunomodulatory cytokine
      response. 

PMID- 25595647
TI  - Alcohol-induced ciliary dysfunction targets the outer dynein arm.
AB  - Alcohol abuse results in an increased incidence of pulmonary infection, in part
      attributable to impaired mucociliary clearance. Analysis of motility in mammalian
      airway cilia has revealed that alcohol impacts the ciliary dynein motors by a
      mechanism involving altered axonemal protein phosphorylation. Given the highly
      conserved nature of cilia, it is likely that the mechanisms for alcohol-induced
      ciliary dysfunction (AICD) are conserved. Thus we utilized the experimental
      advantages offered by the model organism, Chlamydomonas, to determine the precise
      effects of alcohol on ciliary dynein activity and identify axonemal
      phosphoproteins that are altered by alcohol exposure. Analysis of live cells or
      reactivated cell models showed that alcohol significantly inhibits ciliary
      motility in Chlamydomonas via a mechanism that is part of the axonemal structure.
      Taking advantage of informative mutant cells, we found that alcohol impacts the
      activity of the outer dynein arm. Consistent with this finding, alcohol exposure
      results in a significant reduction in ciliary beat frequency, a parameter of
      ciliary movement that requires normal outer dynein arm function. Using mutants
      that lack specific heavy-chain motor domains, we have determined that alcohol
      impacts the beta- and gamma-heavy chains of the outer dynein arm. Furthermore,
      using a phospho-threonine-specific antibody, we determined that the
      phosphorylation state of DCC1 of the outer dynein arm-docking complex is altered
      in the presence of alcohol, and its phosphorylation correlates with AICD. These
      results demonstrate that alcohol targets specific outer dynein arm components and
      suggest that DCC1 is part of an alcohol-sensitive mechanism that controls outer
      dynein arm activity. 

PMID- 25595648
TI  - Increased IL-33 expression in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease
      characterized by inflammatory cell activation and the release of inflammatory
      mediators. Interleukin-33 (IL-33) plays a critical role in various inflammatory
      and immunological pathologies, but evidence for its role in COPD is lacking. This
      study aimed to investigate the expression of IL-33 in COPD and to determine
      whether IL-33 participates in the initiation and progression of COPD. Levels of
      serum IL-33 and its receptors were measured by ELISA, and serum levels of IL-33,
      ST2, and IL-1 receptor accessory protein were elevated in patients with COPD
      compared with control subjects. Flow cytometry analysis further demonstrated an
      increase in peripheral blood lymphocytes (PBLs) expressing IL-33 in patients with
      COPD. Immunofluorescence analysis revealed that the main cellular source of IL-33
      in lung tissue was human bronchial epithelial cells (HBEs). Cigarette smoke
      extract and lipopolysaccharide could enhance the ability of PBLs and HBEs to
      express IL-33. Furthermore, PBLs from patients with COPD showed greater IL-33
      release in response to the stimulus. Collectively, these findings suggest that IL
      33 expression levels are increased in COPD and related to airway and systemic
      inflammation. Therefore, IL-33 might contribute to the pathogenesis and
      progression of this disease.

PMID- 25595649
TI  - Augmentation of the effects of vasoactive intestinal peptide aerosol on pulmonary
      hypertension via coapplication of a neutral endopeptidase 24.11 inhibitor.
AB  - A deficiency of the pulmonary vasodilative vasoactive intestinal peptide (VIP)
      has been suggested to be involved in the pathophysiology of pulmonary
      hypertension (PH). Supplementation of VIP as an aerosol is hampered by the fact
      that it is rapidly inactivated by neutral endopeptidases (NEP) located on the
      lung surface. Coapplication of thiorphan, an NEP 24.11 inhibitor, could augment
      the biological effects of inhaled VIP alone. A stable pulmonary vasoconstriction
      with a threefold increase of pulmonary artery pressure was established by
      application the thromboxane mimetic U46619 in the isolated rabbit lung model. VIP
      and thiorphan were either applied intravascularly or as an aerosol. VIP caused a
      significant pulmonary vasodilation either during intravascular application or
      inhalation. These effects were of short duration. Thiorphan application had no
      effects on pulmonary vasoconstriction per se but significantly augmented the
      effects of VIP aerosol. Thiorphan, not only augmented the maximum hemodynamic
      effects of VIP aerosol, but also led to a significant prolongation of these
      effects. VIP causes pulmonary vasodilation in a model of acute experimental PH.
      The hemodynamic effects of VIP aerosol can be significantly augmented via
      coapplication of an NEP inhibitor. 

PMID- 25595650
TI  - Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular
      remodeling, and collagen deposition in neonatal rat lungs.
AB  - Arginase is an enzyme that limits substrate L-arginine bioavailability for the
      production of nitric oxide by the nitric oxide synthases and produces L
      ornithine, which is a precursor for collagen formation and tissue remodeling. We
      studied the pulmonary vascular effects of arginase inhibition in an established
      model of repeated systemic bleomycin sulfate administration in neonatal rats that
      results in pulmonary hypertension and lung injury mimicking the characteristics
      typical of bronchopulmonary dysplasia. We report that arginase expression is
      increased in the lungs of bleomycin-exposed neonatal rats and that treatment with
      the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin
      induced development of pulmonary hypertension and deposition of collagen.
      Arginase inhibition resulted in increased L-arginine and L-arginine
      bioavailability and increased pulmonary nitric oxide production. Arginase
      inhibition also normalized the expression of inducible nitric oxide synthase, and
      reduced bleomycin-induced nitrative stress while having no effect on bleomycin
      induced inflammation. Our data suggest that arginase is a promising target for
      therapeutic interventions in neonates aimed at preventing lung vascular
      remodeling and pulmonary hypertension.

PMID- 25595652
TI  - Changes in tumour volume and motion during radiotherapy for thoracic oesophageal
      cancer.
AB  - BACKGROUND AND PURPOSE: Variations of target volume and position were important
      factors in correction of radiotherapy planning. The purpose was to investigate
      the changes in volume and motion of oesophageal cancer during radiotherapy using
      four-dimensional computed tomography (4D-CT). METHODS AND MATERIALS: In total,
      109 enhanced 4D-CT data sets were acquired for 38 patients throughout treatment.
      Gross tumour volumes (GTVs) were outlined on each data set. Variations in volume,
      motion, and position were calculated for GTV and internal GTV (IGTV) during
      treatment. RESULTS: GTV (25%, P<0.01) and IGTV (27%, P<0.01) had decreased
      significantly when measured at the twentieth fraction. Larger intrafractional GTV
      centre shifts (P<0.01) were observed in the superior-inferior direction (median
      value of 3.1mm) compared with the right-left and anterior-posterior directions
      (1.6mm and 1.4mm, respectively). The interfractional shift of the IGTV centre was
      not significant during radiotherapy. The overlap ratios of the targets decreased
      for both GTV and IGTV during treatment. CONCLUSIONS: Variations in GTV and IGTV
      centre shifts were not significant throughout treatment. However, tumour volume
      decreased significantly by the twentieth fraction. Finally, changes in
      oesophageal tumour volume and motion may decrease the overlap ratio for GTV and
      IGTV during radiotherapy.

PMID- 25595651
TI  - Infection of mice with influenza A/WSN/33 (H1N1) virus alters alveolar type II
      cell phenotype.
AB  - Influenza viruses cause acute respiratory disease of great importance to public
      health. Alveolar type II (ATII) respiratory epithelial cells are central to
      normal lung function and are a site of influenza A virus replication in the
      distal lung. However, the consequences of infection for ATII cell function are
      poorly understood. To determine the impact of influenza infection on ATII cells
      we used C57BL/6-congenic SP-C(GFP) mice that express green fluorescent protein
      (GFP) under the control of the surfactant protein-C (SP-C) promoter, which is
      only active in ATII cells. Most cells isolated from the lungs of uninfected SP
      C(GFP) mice were GFP(+) but did not express the alveolar type I (ATI) antigen
      podoplanin (PODO). ATII cells were also EpCAM(+) and alpha2,3-linked
      sialosaccharide(+). Infection with influenza A/WSN/33 virus caused severe
      hypoxemia and pulmonary edema. This was accompanied by loss of whole lung GFP
      fluorescence, reduced ATII cell yields, increased ATII cell apoptosis, reduced SP
      C gene and protein expression in ATII cell lysates, and increased PODO gene and
      protein levels. Flow cytometry indicated that infection decreased GFP(+)/PODO(-)
      cells and increased GFP(-)/PODO(+) and GFP(-)/PODO(-) cells. Very few
      GFP(+)/PODO(+) cells were detectable. Finally, infection resulted in a
      significant decline in EpCAM expression by PODO(+) cells, but had limited effects
      on alpha2,3-linked sialosaccharides. Our findings indicate that influenza
      infection results in a progressive differentiation of ATII cells into ATI-like
      cells, possibly via an SP-C(-)/PODO(-) intermediate, to replace dying or dead ATI
      cells. However, impaired SP-C synthesis is likely to contribute significantly to
      reduced lung compliance in infected mice.

PMID- 25595653
TI  - The diagnostic criteria and structure of catatonia.
AB  - BACKGROUND: The classification of catatonia has fluctuated and underwent recent
      changes in DSM-5. The current study examines the prevalence of catatonia signs,
      estimates the utility of diagnostic features, identifies core catatonia signs,
      and explores their underlying structure. METHOD: We screened 339 acutely ill
      medical and psychiatric patients with the Bush Francis Catatonia Rating Scale
      (BFCRS). We examined prevalence and severity of catatonia signs and compared
      BFCRS, DSM-IV and DSM-5 diagnoses. We used principal component analysis (PCA) to
      examine the factorial validity of catatonia and item response theory (IRT) to
      estimate each sign's utility and reliability. RESULTS: Out of the 339 patients,
      300 were diagnosed with catatonia using the BFCRS and 232 catatonia diagnoses
      were validated by the treating provider based on selection for treatment with
      benzodiazepines or electroconvulsive therapy. Of the 232 validated catatonia
      cases, 211 (91%) met DSM-IV criteria but only 170 (73%) met DSM-5 criteria for
      catatonia. Staring was the most prevalent catatonia sign. PCA identified three
      components, interpretable as "Increased, Abnormal and Decreased Psychomotor
      Activity," although 63% of the variance was unexplained. IRT showed that
      Excitement, Waxy Flexibility and Immobility/Stupor were the best indicators of
      each factor. The BFCRS had many redundant items and as a whole had low
      reliability at low severity of catatonia, but good reliability at moderate-high
      severity of catatonia. CONCLUSIONS: The structure of catatonia remains to be
      discovered.

PMID- 25595654
TI  - Blunted brain activation in patients with schizophrenia in response to emotional
      cognitive inhibition: a functional near-infrared spectroscopy study.
AB  - INTRODUCTION: Patients with schizophrenia (SZ) have deficits of facial emotion
      processing and cognitive inhibition, but the brain pathophysiology underlying
      these deficits and their interaction are not clearly understood. We tested brain
      activity during an emotional face go/no-go task that requires rapid executive
      control affected by emotional stimuli in patients with SZ using functional near
      infrared spectroscopy (fNIRS). METHODS: Twenty-five patients with SZ and 28
      healthy control subjects were studied. We evaluated behavioral performance and
      used fNIRS to measure oxygenated hemoglobin concentration changes in fronto
      temporal areas during the emotional go/no-go task with emotional and non
      emotional blocks. RESULTS: Patients with SZ made more errors and had longer
      reaction times in both test blocks compared with healthy subjects. Significantly
      greater activation in the inferior, superior, middle, and orbital frontal regions
      were observed in healthy subjects during the emotional go/no-go block compared to
      the non-emotional go/no-go block, but this difference was not observed in
      patients with SZ. Relative to healthy subjects, patients with SZ showed less
      activation in the superior and orbital frontal and middle temporal regions during
      the emotional go/no-go block. DISCUSSION: Our results suggest that fronto
      temporal dysfunction in patients with SZ is due to an interaction between
      abnormal processing of emotional facial expressions with negative valence and
      cognitive inhibition, especially during the rapid selection of rule-based
      associations that override automatic emotional response tendencies. They indicate
      that fronto-temporal dysfunction is involved in the pathophysiology of emotional
      cognitive deficits in patients with SZ.

PMID- 25595655
TI  - Approach to molecular characterization of different strains of Fasciola hepatica
      using random amplified polymorphic DNA polymerase chain reaction.
AB  - The aim of the present study was to genetically characterize Fasciola hepatica
      strains from diverse ecogeographical regions (America and Europe), susceptible
      and resistant to Triclabendazole, using the random amplified polymorphic DNA
      fragments (RAPDs-PCR) technique to elucidate genetic variability between the
      different isolates. Ten different oligonucleotide primers of 10 bases with GC
      content varying from 50-70% were used. A polymerase chain reaction (PCR) was
      carried out in 25 MUl of total volume. Duplicate PCR reactions on each individual
      template DNA were performed to test the reproducibility of the individual DNA
      bands. The size of the RAPD-PCR fragments was determined by the reciprocal plot
      between the delay factors (Rf) versus the logarithm of molecular weight ladder.
      The phenogram obtained showed three main clusters, the major of which contained
      European Strains (Cullompton and Sligo) showing a genetic distance of 27.2
      between them. The American strains (Cedive and Cajamarca) on the other hand
      formed each their distinctive group but clearly maintaining a closer genetic
      relationship among them than that to their European counterparts, with which
      showed a distance of 33.8 and 37.8, respectively. This polymorphism would give
      this species enhanced adaptability against the host, as well as the environment.
      The existence of genetically different populations of F. hepatica could allow,
      against any selection pressure, natural or artificial (for use fasciolicides
      products and/or control measures), one or more populations of F. hepatica to be
      able to survive and create resistance or adaptability to such selective pressure.

PMID- 25595656
TI  - Development and optimization of cocktail-ELISA for a unified surveillance of
      zoonotic schistosomiasis in multiple host species.
AB  - The zoonotic characteristic of the human parasite Schistosoma japonicum infecting
      a significant number of wild and domestic animals highlights the need to develop
      a unified surveillance in multiple host species for a strengthened
      schistosomiasis control. It has been shown in several studies that water
      buffaloes and dogs are considered important reservoirs in the transmission of the
      schistosome parasite to humans. Recombinant antigens like thioredoxin peroxidase
      1 (SjTPx-1) and tandem repeat proteins (Sj1TR, Sj7TR) have been shown to be good
      diagnostic antigens individually in humans, water buffaloes, and dogs in previous
      studies. Mixing these antigens together in a cocktail-ELISA might not only
      improve their diagnostic potentials but rather produce a multi-host species
      detection means for zoonotic schistosomiasis. In this study, we aimed to develop
      and optimize cocktail-ELISA by testing different combinations of these
      recombinant antigens in humans, water buffaloes, and dogs. As compared with the
      diagnostic potential calculated for each of the three recombinant antigens used,
      their combination has presented improved specificities, positive predictive
      values, and kappa values. Using samples collected from various endemic areas in
      the Philippines, results showed that the combination of SjTPx-1/Sj7TR/Sj1TR has
      the highest sensitivity in humans (84.1 %), water buffaloes, and dogs (80 %) and
      specificity (100 %) in all host species. This study therefore suggests the use of
      cocktail-ELISA in improving the zoonotic surveillance in schistosomiasis endemic
      areas.

PMID- 25595657
TI  - Molecular phylogeny and diagnosis of species of the family Protostrongylidae from
      caprine hosts in Uzbekistan.
AB  - Protostrongylids are important pulmonary parasites of ungulates, particularly
      caprines. Their complex life cycles involve terrestrian gastropods as
      intermediate hosts. Morphological discrimination of larvae in feces and snails is
      impossible to the species level, and molecular data are missing for many species.
      To improve diagnosis and epidemiology of protostrongylids, this study describes
      internal transcribed spacer 2 (ITS-2) sequences for five protostrongylid and one
      metastrongylid species from Uzbekistan. Morphological and molecular analyses
      identified Protostrongylus rufescens, Protostrongylus hobmaieri, Protostrongylus
      sp., Spiculocaulus leuckarti, and Cystocaulus ocreatus. Sequence differences
      between ITS-2 were sufficient to allow species identification, e.g., in the
      Protostrongylinae intraspecific and interspecific genetic distances ranged
      between 0-0.01 and 0.05 and 0.16, respectively. There was one exception in the
      Elaphostrongylidae with identical ITS-2 sequences in Elaphostrongylus cervi and
      Elaphostrongylus rangiferi questioning their status as valid species. Maximum
      likelihood analysis sequences largely supported the currently assumed
      phylogenetic relationships among Protostrongylidae as predicted using
      morphological characters. The monophyly of the subfamilies Varestrongylinae,
      Elaphostrongylinae, and Protostrongylinae was corroborated with support values in
      Shimodaira-Hasegawa or Bayesian modifications of the approximate likelihood ratio
      test (aLRT) >=97%, but support for Muellerinae was weak (8 and 52%, respectively)
      since Muellerius capillaris differs significantly from the other Muellerinae. On
      the genus level, paraphyly of the genus Protostrongylus was confirmed since the
      members of the genera Spiculocaulus and Orthostrongylus were located within the
      Protostrongylus cluster (aLRT >=99%). Maximum likelihood unequivocally assigned
      every unique sequence to the correct species confirming suitability of ITS-2
      regions for diagnosis protostrongylids except of E. cervi and E. rangiferi.

PMID- 25595658
TI  - The neuroprotective role of metformin in advanced glycation end product treated
      human neural stem cells is AMPK-dependent.
AB  - Diabetic neuronal damage results from hyperglycemia followed by increased
      formation of advanced glycosylation end products (AGEs), which leads to
      neurodegeneration, although the molecular mechanisms are still not well
      understood. Metformin, one of the most widely used anti-diabetic drugs, exerts
      its effects in part by activation of AMP-activated protein kinase (AMPK). AMPK is
      a critical evolutionarily conserved enzyme expressed in the liver, skeletal
      muscle and brain, and promotes cellular energy homeostasis and biogenesis by
      regulating several metabolic processes. While the mechanisms of AMPK as a
      metabolic regulator are well established, the neuronal role for AMPK is still
      unknown. In the present study, human neural stem cells (hNSCs) exposed to AGEs
      had significantly reduced cell viability, which correlated with decreased AMPK
      and mitochondria associated gene/protein (PGC1alpha, NRF-1 and Tfam) expressions,
      as well as increased activation of caspase 3 and 9 activities. Metformin
      prevented AGEs induced cytochrome c release from mitochondria into cytosol in the
      hNSCs. Co-treatment with metformin significantly abrogated the AGE-mediated
      effects in hNSCs. Metformin also significantly rescued hNSCs from AGE-mediated
      mitochondrial deficiency (lower ATP, D-loop level, mitochondrial mass, maximal
      respiratory function, COX activity, and mitochondrial membrane potential).
      Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE
      mediated reductions in the expression levels of several neuroprotective genes
      (PPARgamma, Bcl-2 and CREB). These findings extend our understanding of the
      molecular mechanisms of both AGE-induced neuronal toxicity, and AMPK-dependent
      neuroprotection by metformin. This study further suggests that AMPK may be a
      potential therapeutic target for treating diabetic neurodegeneration. 

PMID- 25595660
TI  - It's complicated: The relation between cognitive change procedures, cognitive
      change, and symptom change in cognitive therapy for depression.
AB  - Many attempts have been made to discover and characterize the mechanisms of
      change in psychotherapies for depression, yet no clear, evidence-based account of
      the relationship between therapeutic procedures, psychological mechanisms, and
      symptom improvement has emerged. Negatively-biased thinking plays an important
      role in the phenomenology of depression, and most theorists acknowledge that
      cognitive changes occur during successful treatments. However, the causal role of
      cognitive change procedures in promoting cognitive change and alleviating
      depressive symptoms has been questioned. We describe the methodological and
      inferential limitations of the relevant empirical investigations and provide
      recommendations for addressing them. We then develop a framework within which the
      possible links between cognitive procedures, cognitive change, and symptom change
      can be considered. We conclude that cognitive procedures are effective in
      alleviating symptoms of depression and that cognitive change, regardless of how
      it is achieved, contributes to symptom change, a pattern of findings that lends
      support to the cognitive theory of depression. 

PMID- 25595659
TI  - Peroxide-mediated oxidation and inhibition of the peptidyl-prolyl isomerase Pin1.
AB  - Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that plays a
      critical role in mediating protein conformational changes involved in signaling
      processes related to cell cycle control. Pin1 has also been implicated as being
      neuroprotective in aging-related neurodegenerative disorders including
      Alzheimer's disease where Pin1 activity is diminished. Notably, recent proteomic
      analysis of brain samples from patients with mild cognitive impairment revealed
      that Pin1 is oxidized and also displays reduced activity. Since the Pin1 active
      site contains a functionally critical cysteine residue (Cys113) with a low
      predicted pK(a), we hypothesized that Cys113 is sensitive to oxidation.
      Consistent with this hypothesis, we observed that treatment of Pin1 with hydrogen
      peroxide results in a 32Da mass increase, likely resulting from the oxidation of
      Cys113 to sulfinic acid (Cys-SO(2)H). This modification results in loss of
      peptidyl-prolyl isomerase activity. Notably, Pin1 with Cys113 substituted by
      aspartic acid retains activity and is no longer sensitive to oxidation.
      Structural studies by X-ray crystallography revealed increased electron density
      surrounding Cys113 following hydrogen peroxide treatment. At lower concentrations
      of hydrogen peroxide, oxidative inhibition of Pin1 can be partially reversed by
      treatment with dithiothreitol, suggesting that oxidation could be a reversible
      modification with a regulatory role. We conclude that the loss of Pin1 activity
      upon oxidation results from oxidative modification of the Cys113 sulfhydryl to
      sulfenic (Cys-SOH) or sulfinic acid (Cys-SO(2)H). Given the involvement of Pin1
      in pathological processes related to neurodegenerative diseases and to cancer,
      these findings could have implications for the prevention or treatment of
      disease.

PMID- 25595662
TI  - Sex, statins, and statistics.

PMID- 25595661
TI  - Vasoprotective effects of neurocompensatory response to balloon injury during
      diabetes involve the improvement of Mas signaling by TGFbeta1 activation.
AB  - Balloon injury in diabetic rats triggers a sensory neurocompensatory response
      that restores the blood flow in contralateral carotid. These vasoprotective
      effects result from H2O2-mediated relaxation that counteracts AT1-dependent
      contractile hyperreactivity. The most important mechanism from the renin
      angiotensin-system in counteracting AT1-mediated effects is that one is mediated
      by Mas receptors. Thus, we hypothesized that the vasoprotective effects of
      balloon neurocompensation in diabetic rats could result from the improvement of
      Mas signaling by H2O2-mediated sensory mechanisms. NK1 receptors are sensory
      components whose activation could lead to H2O2 generation upon TGFbeta1 release
      and ALK5-mediated Nox4 upregulation. Based on this, we aimed to investigate: (1)
      the role of the TGFbeta1/ALK5-Nox4-H2O2 pathway on modulating Mas signaling in
      diabetic rat contralateral carotid; and (2) the contribution of Mas signaling in
      the control of local blood flow. Our results showed that balloon
      neurocompensation restored diabetic rat contralateral carotid flow by improving
      Mas signaling through NK1-mediated TGFbeta1 release. TGFbeta1/ALK5 activation
      enhanced Nox4 expression and Nox4-driven generation of H2O2. In turn, H2O2
      enhanced the local Mas-mediated relaxation. Since restenosis impairs diabetic rat
      ipsilateral carotid flow, the restoration of diabetic rat contralateral carotid
      flow may prevent further damages in cerebral irrigation by carotid pathways after
      angioplasty during diabetes. 

PMID- 25595664
TI  - Advanced Joystick Algorithms for Computer Access Tasks.
AB  - OBJECTIVE: To compare 2 correction algorithms and 2 joysticks (a conventional
      movement-sensing joystick and a custom-designed isometric joystick) in computer
      access tasks. DESIGN: Repeated-measures, within-subject. SETTING: National
      Veterans Wheelchair Games. PARTICIPANTS: Fifteen participants with various
      diagnoses including multiple sclerosis, spinal cord injury, traumatic brain
      injury, Wilson disease, and Parkinson disease. METHODS: A computer access test
      scenario was used to evaluate the effects of applying proportional integral
      derivative (PID)-based and least means-based algorithms to suppress unintentional
      cursor motions by users with upper extremity spasticity. MAIN OUTCOME MEASURES:
      Trial completion time, reaction time, and trajectory-based measures: movement
      offset, movement variability, and percentage of out-of-path motion on test
      tracks. RESULTS: The quantitative outcome measures showed a high correlation with
      clinical measures for spasticity and functional independence. On small test
      tracks, compared to when no correction algorithms were used, both algorithms
      performed equally well in suppressing unintentional cursor motions. On longer
      test tracks, participants navigated most accurately while using the PID
      algorithm. Participants moved the cursor more accurately using the isometric
      joystick compared to the movement-sensing joystick, with only a slight increase
      in the task completion times. CONCLUSIONS: The joysticks and the advanced
      correction algorithms show promise for use in wide-ranging applications as
      control interfaces.

PMID- 25595663
TI  - Nonthermal plasma--A tool for decontamination and disinfection.
AB  - By definition, the nonthermal plasma (NTP) is partially ionized gas where the
      energy is stored mostly in the free electrons and the overall temperature remains
      low. NTP is widely used for many years in various applications such as low
      temperature plasma chemistry, removal of gaseous pollutants, in gas-discharge
      lamps or surface modification. However, during the last ten years, NTP usage
      expanded to new biological areas of application like plasma microorganisms'
      inactivation, ready-to-eat food preparation, biofilm degradation or in
      healthcare, where it seems to be important for the treatment of cancer cells and
      in the initiation of apoptosis, prion inactivation, prevention of nosocomial
      infections or in the therapy of infected wounds. These areas are presented and
      documented in this paper as a review of representative publications. 

PMID- 25595666
TI  - Ethical considerations in stem cell research on neurologic and orthopedic
      conditions.
AB  - The range and gravity of ethical considerations in stem cell research are
      remarkable and, quite possibly, unprecedented. From the point of securing stem
      cells for implantation, through the translational and first-in-humans process,
      and then proceeding through clinical trials culminating in product or service
      line launch, the entire research trajectory is replete with risk, uncertainty,
      and problems overweighing foreseeable harms against hoped-for benefits. This
      article offers an overview of some of the most salient ethical challenges of stem
      cell research, including ones involving moral status, the intersection of
      research risks and informed consent processes, methodologic considerations in
      early phase 1 trials, the temptation to exaggerate the benefits of research
      discoveries, managing conflicts of interest, and the ethical obligation to
      conduct various monitoring practices throughout a trial, which could last years.
      The article will conclude with a glimpse into the future of these technologies
      wherein the need for ethical scrutiny will likely not diminish. 

PMID- 25595665
TI  - Strategy Training During Inpatient Rehabilitation May Prevent Apathy Symptoms
      After Acute Stroke.
AB  - BACKGROUND: Apathy, or lack of motivation for goal-directed activities,
      contributes to reduced engagement in and benefit from rehabilitation, impeding
      recovery from stroke. OBJECTIVE: To examine the effects of strategy training, a
      behavioral intervention used to augment usual inpatient rehabilitation, on apathy
      symptoms over the first 6 months after stroke. DESIGN: Secondary analysis of
      randomized controlled trial. SETTING: Acute inpatient rehabilitation.
      PARTICIPANTS: Participants with acute stroke who exhibited cognitive impairments
      (Quick Executive Interview Scores >=3) and were admitted for inpatient
      rehabilitation were randomized to receive strategy training (n = 15, 1 session
      per day, 5 days per week, in addition to usual inpatient rehabilitation) or
      reflective listening (n = 15, same dose). METHODS: Strategy training sessions
      focused on participant-selected goals and participant-derived strategies to
      address these goals, using a global strategy training method (Goal-Plan-Do
      Check). Reflective listening sessions focused on participant reflections on their
      rehabilitation goals and experiences, facilitated by open-ended questions and
      active listening skills (attending, following, and responding). MAIN OUTCOME
      MEASURES: Trained raters blinded to group assignment administered the Apathy
      Evaluation Scale at study admission, 3 months, and 6 months. Data were analyzed
      with repeated-measures fixed-effects models. RESULTS: Participants in both groups
      had similar subsyndromal levels of apathy symptoms at study admission (strategy
      training, mean = 25.79, standard deviation = 7.62; reflective listening, mean =
      25.18, standard deviation = 4.40). A significant group * time interaction (F2,28
      = 3.61, P = .040) indicated that changes in apathy symptom levels differed
      between groups over time. The magnitude of group differences in change scores was
      large (d = -0.99, t28 = -2.64, P = .013) at month 3 and moderate to large (d = 
      0.70, t28 = -1.86, P = .073) at month 6. CONCLUSION: Strategy training shows
      promise as an adjunct to usual rehabilitation for maintaining low levels of
      poststroke apathy.

PMID- 25595667
TI  - Reduced serum chemerin in patients with more severe liver cirrhosis.
AB  - Chemerin is a well-established modulator of immune cell function and its serum
      levels are induced in inflammatory diseases. Liver cirrhosis is associated with
      inflammation which is aggravated by portal hypertension. The objective of this
      study was to evaluate whether chemerin is induced in patients with more severe
      liver cirrhosis and portal hypertension. Chemerin has been measured by ELISA in
      the portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous
      serum (HVS) of 45 patients with liver cirrhosis. Chemerin is higher in HVS
      compared to PVS in accordance with our recently published finding. SVS, HVS and
      PVS chemerin decline in patients with more advanced liver injury defined by the
      CHILD-PUGH score. Hepatic chemerin has been determined in a small cohort and is
      similarly expressed in normal and cirrhotic liver. MELD score and serum markers
      of liver and kidney function do not correlate with chemerin. There is a positive
      correlation of chemerin in all compartments with Quick prothrombin time and of
      SVS chemerin with systolic blood pressure. PVS chemerin is induced in patients
      with modest/massive ascites but this does not translate into higher HVS and SVS
      levels. Chemerin is not associated with variceal size. Reduction of portal
      pressure by transjugular intrahepatic portosystemic shunt does not affect
      chemerin levels. These data show that low chemerin in patients with more severe
      liver cirrhosis is associated with reduced Quick prothrombin time. 

PMID- 25595668
TI  - Rupture of abdominal aortic aneurysm in the low wall stress zone.

PMID- 25595669
TI  - Change of regional choroid thickness after reduced-fluence photodynamic therapy
      for chronic central serous chorioretinopathy.
AB  - PURPOSE: To evaluate macular choroidal thickness after reduced-fluence
      photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC).
      DESIGN: Prospective, consecutive, interventional case series. METHODS: Twenty-two
      eyes with chronic CSC were treated with reduced-fluence PDT. Macular choroidal
      thickness was examined using spectral-domain optical coherence tomography with a
      3-dimensinonal radial scan protocol in the choroidal mode before and 1, 3, and 6
      months after the treatment. The mean choroidal thickness in the Early Treatment
      Diabetic Retinopathy Study grid (center, inner circle, and outer circle) was
      compared between before and after therapy, as well as between treated eyes and 54
      volunteer normal eyes. RESULTS: Chronic CSC eyes showed significantly thicker
      choroids in the macular area compared with normal controls (P < .0001). After the
      single treatment session, subretinal fluid resolved completely in all eyes, and
      there were no recurrences during the study period. Choroidal thickness within the
      center area and inner circle showed a significant reduction at all time points
      after treatment (P < .05). The choroidal thickness in the outer circle showed a
      statistically significant reduction at 1 and 3 months but not at 6 months. After
      treatment, the choroidal thickness reduced to the normal values at the center and
      inner circle, but was still significantly thicker in the outer circle (P < .01).
      CONCLUSION: Chronic CSC eyes showed significantly thicker choroids in the macular
      area. After reduced-fluence PDT, macular choroidal thickness became thinner
      within 6 months of treatment.

PMID- 25595670
TI  - Long-term visual prognosis of peripheral multifocal chorioretinitis.
AB  - PURPOSE: To report on the clinical manifestations, complications, and long-term
      visual prognosis of patients with peripheral multifocal chorioretinitis and to
      search for predictors for a lower visual outcome. DESIGN: Retrospective
      consecutive observational case series. METHODS: setting: Institutional. PATIENT
      POPULATION: 134 eyes in 69 patients with a minimum follow-up period of 5 years.
      OBSERVATION PROCEDURE: Clinical characteristics were recorded as well as the
      visual acuity (VA) at the onset of uveitis; after 1, 5, and 10 years; and at the
      end of the follow-up period. MAIN OUTCOME MEASURES: Visual acuity, clinical
      features and complications, required medications and surgeries. RESULTS: The
      majority of the patients were elderly women with chronic bilateral ocular
      involvement, who developed multiple ocular complications over time. Systemic
      sarcoidosis was present in 39% of patients. In addition to peripheral retinal
      lesions and vitritis, papillitis was present in 95% of cases. The major
      complications included macular edema (91%), cataract (93%), glaucoma (35%), and
      optic disc atrophy (25%). The treatment regimens included systemic
      corticosteroids and/or immunosuppressive drugs in 44% of patients, and 84% of
      patients required intraocular surgery. One third of the affected eyes developed
      VA <20/40 at 5-10 years of follow-up. VA at 1 year was the most important
      predictor of visual outcome at 5 and 10 years (P < .001). CONCLUSIONS: Peripheral
      multifocal chorioretinitis was associated with a high prevalence of cataract,
      macular edema, optic disc atrophy, and glaucoma. Despite the chronic course of
      the disease, multiple complications, and surgical interventions, the majority of
      patients achieved satisfactory long-term visual acuity.

PMID- 25595671
TI  - Molecular basis of major psychiatric diseases such as schizophrenia and
      depression.
AB  - Recently several potential susceptibility genes for major psychiatric disorders
      (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1),
      dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have
      been reported. DISC1 is involved in neural development directly via adhesion
      molecules or via its binding partners of DISC1 such as elongation protein zeta-1
      (FEZ1), DISC1-binding zinc-finger protein (DBZ) and kendrin. PACAP also regulates
      neural development via stathmin 1 or via regulation of the DISC1-DBZ binding.
      Dysbindin is also involved in neural development by regulating centrosomal
      microtubule network formation. All such molecules examined to date are involved
      in neural development. Thus, these findings provide new molecular insights into
      the mechanisms of neural development and neuropsychiatric disorders. On the other
      hand, in addition to neurons, both DISC and DBZ have been detected in
      oligodendrocytes and implicated in regulating oligodendrocyte differentiation.
      DISC1 inhibits the differentiation of oligodendrocyte precursor cells into
      oligodendrocytes, while DBZ has a positive regulatory role in oligodendrocyte
      differentiation. Evidence suggesting that disturbance of oligodendrocyte
      development causes major depression is also described.

PMID- 25595673
TI  - Classifying GABAergic interneurons with semi-supervised projected model-based
      clustering.
AB  - OBJECTIVES: A recently introduced pragmatic scheme promises to be a useful
      catalog of interneuron names. We sought to automatically classify digitally
      reconstructed interneuronal morphologies according to this scheme.
      Simultaneously, we sought to discover possible subtypes of these types that might
      emerge during automatic classification (clustering). We also investigated which
      morphometric properties were most relevant for this classification. MATERIALS AND
      METHODS: A set of 118 digitally reconstructed interneuronal morphologies
      classified into the common basket (CB), horse-tail (HT), large basket (LB), and
      Martinotti (MA) interneuron types by 42 of the world's leading neuroscientists,
      quantified by five simple morphometric properties of the axon and four of the
      dendrites. We labeled each neuron with the type most commonly assigned to it by
      the experts. We then removed this class information for each type separately, and
      applied semi-supervised clustering to those cells (keeping the others' cluster
      membership fixed), to assess separation from other types and look for the
      formation of new groups (subtypes). We performed this same experiment unlabeling
      the cells of two types at a time, and of half the cells of a single type at a
      time. The clustering model is a finite mixture of Gaussians which we adapted for
      the estimation of local (per-cluster) feature relevance. We performed the
      described experiments on three different subsets of the data, formed according to
      how many experts agreed on type membership: at least 18 experts (the full data
      set), at least 21 (73 neurons), and at least 26 (47 neurons). RESULTS:
      Interneurons with more reliable type labels were classified more accurately. We
      classified HT cells with 100% accuracy, MA cells with 73% accuracy, and CB and LB
      cells with 56% and 58% accuracy, respectively. We identified three subtypes of
      the MA type, one subtype of CB and LB types each, and no subtypes of HT (it was a
      single, homogeneous type). We got maximum (adapted) Silhouette width and ARI
      values of 1, 0.83, 0.79, and 0.42, when unlabeling the HT, CB, LB, and MA types,
      respectively, confirming the quality of the formed cluster solutions. The
      subtypes identified when unlabeling a single type also emerged when unlabeling
      two types at a time, confirming their validity. Axonal morphometric properties
      were more relevant that dendritic ones, with the axonal polar histogram length in
      the [pi, 2pi) angle interval being particularly useful. CONCLUSIONS: The applied
      semi-supervised clustering method can accurately discriminate among CB, HT, LB,
      and MA interneuron types while discovering potential subtypes, and is therefore
      useful for neuronal classification. The discovery of potential subtypes suggests
      that some of these types are more heterogeneous that previously thought. Finally,
      axonal variables seem to be more relevant than dendritic ones for distinguishing
      among the CB, HT, LB, and MA interneuron types.

PMID- 25595672
TI  - The DNA damage response and checkpoint adaptation in Saccharomyces cerevisiae:
      distinct roles for the replication protein A2 (Rfa2) N-terminus.
AB  - In response to DNA damage, two general but fundamental processes occur in the
      cell: (1) a DNA lesion is recognized and repaired, and (2) concomitantly, the
      cell halts the cell cycle to provide a window of opportunity for repair to occur.
      An essential factor for a proper DNA-damage response is the heterotrimeric
      protein complex Replication Protein A (RPA). Of particular interest is
      hyperphosphorylation of the 32-kDa subunit, called RPA2, on its serine/threonine
      rich amino (N) terminus following DNA damage in human cells. The unstructured N
      terminus is often referred to as the phosphorylation domain and is conserved
      among eukaryotic RPA2 subunits, including Rfa2 in Saccharomyces cerevisiae. An
      aspartic acid/alanine-scanning and genetic interaction approach was utilized to
      delineate the importance of this domain in budding yeast. It was determined that
      the Rfa2 N-terminus is important for a proper DNA-damage response in yeast,
      although its phosphorylation is not required. Subregions of the Rfa2 N-terminus
      important for the DNA-damage response were also identified. Finally, an Rfa2 N
      terminal hyperphosphorylation-mimetic mutant behaves similarly to another Rfa1
      mutant (rfa1-t11) with respect to genetic interactions, DNA-damage sensitivity,
      and checkpoint adaptation. Our data indicate that post-translational modification
      of the Rfa2 N-terminus is not required for cells to deal with "repairable" DNA
      damage; however, post-translational modification of this domain might influence
      whether cells proceed into M-phase in the continued presence of unrepaired DNA
      lesions as a "last-resort" mechanism for cell survival. 

PMID- 25595674
TI  - Anti-inflammatory effects of BHBA in both in vivo and in vitro Parkinson's
      disease models are mediated by GPR109A-dependent mechanisms.
AB  - BACKGROUND: Accumulating evidence suggests that neuroinflammation plays an
      important role in the progression of Parkinson's disease (PD). Excessively
      activated microglia produce several pro-inflammatory enzymes and pro-inflammatory
      cytokines, leading to damage to surrounding neurons and eventually inducing
      neurodegeneration. Therefore, the inhibition of microglial overactivation may be
      a potential therapeutic strategy to prevent the further progression of PD. beta
      Hydroxybutyric acid (BHBA) has been shown to suppress lipopolysaccharide (LPS)
      induced inflammation in BV-2 cells and to protect dopaminergic neurons in
      previous studies, but the underlying mechanisms remain unclear. Thus, in this
      study, we further investigated this mechanism in LPS-induced in vivo and in vitro
      PD models. METHODS: For the in vitro experiments, primary mesencephalic neuron
      glia cultures were pretreated with BHBA and stimulated with LPS. [(3)H]dopamine
      (DA) uptake, tyrosine hydroxylase-immunoreactive (TH-ir) neurons and
      morphological analysis were evaluated and analyzed in primary mesencephalic
      neuron-glia cultures. In vivo, microglial activation and the injury of
      dopaminergic neurons were induced by LPS intranigral injection, and the effects
      of BHBA treatment on microglial activation and the survival ratio and function of
      dopaminergic neurons were investigated. Four our in vitro mechanistic experiment,
      primary microglial cells were pretreated with BHBA and stimulated with LPS; the
      cells were then assessed for the responses of pro-inflammatory enzymes and pro
      inflammatory cytokines, and the NF-kappaB signaling pathway was evaluated and
      analyzed. RESULTS: We found that BHBA concentration-dependently attenuated the
      LPS-induced decrease in [(3)H]DA uptake and loss of TH-ir neurons in the primary
      mesencephalic neuron/glia mixed culture. BHBA treatment significantly improved
      the motor dysfunction of the PD model rats induced by intranigral injection of
      LPS, and this beneficial effect of BHBA was attributed to the inhibition of
      microglial overactivation and the protection of dopaminergic neurons in the
      substantia nigra (SN). Our in vitro mechanistic study revealed that the
      inhibitory effect of BHBA on microglia was mediated by G-protein-coupled receptor
      109A (GPR109A) and involved the NF-kappaB signaling pathway, causing the
      inhibition of pro-inflammatory enzyme (iNOS and COX-2) and pro-inflammatory
      cytokine (TNF-alpha, IL-1beta, and IL-6) production. CONCLUSIONS: In conclusion,
      the present study supports the effectiveness of BHBA in protecting dopaminergic
      neurons against inflammatory challenge.

PMID- 25595677
TI  - A teleconference with three-dimensional surgical video presentation on the
      'usual' Internet.
AB  - Endoscopic surgery employing three-dimensional (3D) video images, such as a
      robotic surgery, has recently become common. However, the number of opportunities
      to watch such actual 3D videos is still limited due to many technical
      difficulties associated with showing 3D videos in front of an audience. A
      teleconference with 3D video presentations of robotic surgeries was held between
      our institution and a distant institution using a commercially available
      telecommunication appliance on the 'usual' Internet. Although purpose-built video
      displays and 3D glasses were necessary, no technical problems occurred during the
      presentation and discussion. This high-definition 3D telecommunication system can
      be applied to discussions about and education on 3D endoscopic surgeries for many
      surgeons, even in distant places, without difficulty over the usual Internet
      connection. 

PMID- 25595676
TI  - Stability of 3-bromotyrosine in serum and serum 3-bromotyrosine concentrations in
      dogs with gastrointestinal diseases.
AB  - BACKGROUND: 3-Bromotyrosine (3-BrY) is a stable product of eosinophil peroxidase
      and may serve as a marker of eosinophil activation. A gas chromatography/mass
      spectrometry method to measure 3-BrY concentrations in serum from dogs has
      recently been established and analytically validated. The aims of this study were
      to determine the stability of 3-BrY in serum, to determine the association
      between peripheral eosinophil counts and the presence of an eosinophilic
      infiltrate in the gastrointestinal tract, and to compare serum 3-BrY
      concentrations in healthy dogs (n = 52) and dogs with eosinophilic
      gastroenteritis (EGE; n = 27), lymphocytic-plasmacytic enteritis (LPE; n = 25),
      exocrine pancreatic insufficiency (EPI; n = 26), or pancreatitis (n = 27).
      RESULTS: Serum 3-BrY concentrations were stable for up to 8, 30, and 180 days at
      4 degrees C, -20 degrees C, and -80 degrees C, respectively. There was no
      significant association between peripheral eosinophil count and the presence of
      eosinophils in the GI tissues (P = 0.1733). Serum 3-BrY concentrations were
      significantly higher in dogs with EGE (median [range] = 5.04 [<=0.63-26.26]
      MUmol/L), LPE (median [range] = 3.60 [<=0.63-15.67] MUmol/L), and pancreatitis
      (median [range] = 1.49 [<=0.63-4.46] MUmol/L) than in healthy control dogs
      (median [range] = <=0.63 [<=0.63-1.79] MUmol/L; P < 0.0001), whereas
      concentrations in dogs with EPI (median [range] = 0.73 [<=0.63-4.59] MUmol/L)
      were not different compared to healthy control dogs. CONCLUSIONS: The present
      study revealed that 3-BrY concentrations were stable in serum when refrigerated
      and frozen. No relationship between peripheral eosinophil count and the presence
      of eosinophils infiltration in the GI tissues was found in this study. In
      addition, serum 3-BrY concentrations were increased in dogs with EGE, but also in
      dogs with LPE and pancreatitis. Further studies are needed to determine whether
      measurement of 3-BrY concentrations in serum may be useful to assess patients
      with suspected or confirmed EGE or LPE.

PMID- 25595675
TI  - n-Nonacosadienes from the marine haptophytes Emiliania huxleyi and Gephyrocapsa
      oceanica.
AB  - The hydrocarbons in cultures of marine haptophytes Emiliania huxleyi NIES837 and
      Gephyrocapsa oceanica NIES1315 were analyzed, and nonacosadienes and
      hentriacontadienes were detected as the major compounds in both strains. C29 and
      C31 monoenes and di-, tri- and tetra-unsaturated C33 alkenes were also detected
      as minor compounds but not C37 and C38 alkenes. The positions of the double bonds
      in the C29 and C31 alkenes were determined by mass spectrometry of their dimethyl
      disulfide (DMDS) adducts. Among the four C29 alkenes identified, the most
      abundant isomer was 2,20-nonacosadiene, and the other three compounds were 1,20
      nonacosadiene, 3,20-nonacosadiene and 9-nonacosene, respectively. Hitherto, 2,20
      nonacosadiene and 3,20-nonacosadiene were unknown to be natural products. The
      double bond at the n-9 (omega9) position in these C29 alkenes is hypothesized to
      be derived from precursors of unsaturated fatty acids possessing an n-9 double
      bond, such as (9Z)-9-octadecenoic acid. Nonacosadienes have the potential for
      being used as distinct haptophyte biomarkers. 

PMID- 25595678
TI  - Identification of novel genes expressed during host infection in Streptococcus
      equi ssp. zooepidemicus ATCC35246.
AB  - Infection with Streptococcus equi ssp. zooepidemicus (Streptococcus
      zooepidemicus, SEZ) can cause septicemia, meningitis, and mastitis in
      domesticated species. Identification of this organism's virulence factors is an
      effective way of clarifying its pathogenic mechanism. We employed in vivo-induced
      antigen technology (IVIAT) to find bacterial genes that were only expressed or
      upregulated in an infected host (IVI genes). Convalescent-phase sera from pigs
      infected with SEZ were pooled, adsorbed against in vitro antigens, and used to
      screen SEZ genomic expression libraries. This analysis identified 43 genes as IVI
      genes. Six of these 43 genes were verified via real-time PCR. Following the
      analysis, we were able to assign a putative function to 36 of the 43 proteins.
      These proteins included those involved in virulence and adaptation; formation of
      intermediary products; gene replication, transcription and expression; energy
      metabolism; transport and also various proteins of unknown function. The
      relationship between sagD gene and bacterial virulence was confirmed. This study
      provides new molecular data for the study of streptococcal disease in swine and
      is important for identifying the pathogenic mechanisms of SEZ. 

PMID- 25595679
TI  - Arsenic trioxide and reduced glutathione act synergistically to augment
      inhibition of thyroid peroxidase activity in vitro.
AB  - Thyroid peroxidase (TPO) is the enzyme involved in thyroid hormone synthesis.
      Arsenic trioxide (As2O3) is known to inhibit TPO activity in vitro. This
      inhibition is believed to occur when As2O3 binds to TPO's free sulfhydryl groups.
      Reduced glutathione (GSH) is also known to inhibit TPO activity in vitro. This
      inhibition may occur because GSH acts as a competitive substrate for hydrogen
      peroxide, or possibly reduce the oxidized form of iodide, requirements for TPO
      action. On the other hand, one could speculate that GSH reduces arsenic-induced
      TPO inhibition by interacting directly with arsenic or TPO, consequently limiting
      arsenic's ability to inhibit TPO activity. Since GSH is known to inhibit thyroid
      hormone synthesis while at the same time it is also known to be an important
      antioxidant preventing cellular damage induced by oxidative stress and protecting
      the thyroid gland from oxidative damage induced by arsenic, we wanted to
      determine if a combination of As2O3 and reduced GSH would either attenuate or
      augment the As2O3-induced inhibition on TPO activity. Using an in vitro system,
      TPO was assayed spectrophotometrically in the presence of As2O3 (0.01, 0.1, 1,
      and 10 ppm), GSH (0.1, 1, 5, and 10 ppm), and As2O3 (0.1 ppm) and GSH (0.01, 0.1,
      1, or 10 ppm) combinations. Our results show that 0.1, 1.0, and 10 ppm As2O3
      inhibit TPO activity. Similarly, 5 and 10 ppm GSH also inhibit TPO activity. When
      0.1 ppm As2O3 (i.e., the lowest dose of arsenic able to partially inhibit TPO
      activity) is combined with 0.01, 0.1, 1.0, or 10 ppm GSH inhibition of in vitro
      TPO activity is augmented as indicated by complete inhibition of TPO. The
      mechanism of this augmentation and whether it translates to living systems
      remains unclear.

PMID- 25595680
TI  - Is the Pharmacological Mode of Action of Chromium(III) as a Second Messenger?
AB  - Although recent studies have shown that chromium (as the trivalent ion) is not an
      essential trace element, it has been demonstrated to generate beneficial effects
      at pharmacologically relevant doses on insulin sensitivity and cholesterol levels
      of rodent models of insulin insensitivity, including models of type 2 diabetes.
      The mode of action of Cr(III) at a molecular level is still an area of active
      debate; however, the movement of Cr(III) in the body, particularly in response to
      changes in insulin concentration, suggests that Cr(III) could act as a second
      messenger, amplifying insulin signaling. The evidence for the pharmacological
      mechanism of Cr(III)'s ability to increase insulin sensitivity by acting as a
      second messenger is reviewed, and proposals for testing this hypothesis are
      described. 

PMID- 25595681
TI  - Discovery of thienoimidazole-based HCV NS5A inhibitors. Part 1: C2-symmetric
      inhibitors with diyne and biphenyl linkers.
AB  - The discovery of C2-symmetric bis-thienoimidazoles HCV NS5A inhibitors is herein
      reported. Two straightforward approaches to access the requisite diyne and
      biphenyl linker moieties are described. This study revealed the paramount
      importance of the aromatic character of the linker to achieve high genotype 1a
      potency. 

PMID- 25595682
TI  - The discovery of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new
      class of respiratory syncytial virus (RSV) fusion inhibitors. Part 1.
AB  - Respiratory syncytial virus (RSV) is a major cause of respiratory tract
      infections in infants, young children and adults. Compound 1a (9b-(4
      chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5
      one) was identified as an inhibitor of A and B strains of RSV targeting the
      fusion glycoprotein. SAR was developed by systematic exploration of the phenyl
      (R(1)) and benzoyl (R(2)) groups. Furthermore, introduction of a nitrogen at the
      8-position of the tricyclic core resulted in active analogues with improved
      properties (aqueous solubility, protein binding and logD) and excellent rat
      pharmacokinetics (e.g., rat oral bioavailability of 89% for compound 17). 

PMID- 25595683
TI  - Two new protein tyrosine phosphatase 1B inhibitors, hyattellactones A and B, from
      the Indonesian marine sponge Hyattella sp.
AB  - Two unique sesterterpenes, hyattellactones A (1) and B (2), together with two
      known sesterterpenes, phyllofolactones F (3) and G (4), were isolated from the
      Indonesian marine sponge Hyattella sp. The structures of the two new compounds, 1
      and 2 were assigned based on their spectroscopic data. Hyattellactone A (1) was a
      scalarane sesterterpene with an alpha,beta-unsaturated-gamma-lactone ring and C
      ethyl group, while B (2) was an epimer of 1 at the C-24 position. Compounds 1 and
      3 inhibited PTP1B activity with IC50 values of 7.45 and 7.47MUM, respectively. On
      the other hand, compounds 2 and 4 (24S-isomers of 1 and 3, respectively) showed
      much reduced activity than the 24R-isomers. 

PMID- 25595684
TI  - Diaminopyrimidines, diaminopyridines and diaminopyridazines as histamine H4
      receptor modulators.
AB  - Previously disclosed H4 receptor modulators, the triamino substituted pyridines
      and pyrimidines, contain a free primary amino (-NH2) group. In this Letter we
      demonstrate that an exocyclic amine (NH2) is not needed to maintain affinity, and
      also show a significant divergence in the SAR of the pendant diamine component.
      These des-NH2 azacycles also show a distinct functional spectrum, that appears to
      be influenced by the diamine component; in the case of the 1,3-amino pyrimidines,
      the preferred diamine is the amino pyrrolidine instead of the more common
      piperazines. Finally, we introduce 3,5-diamino pyridazines as novel histamine H4
      antagonists. 

PMID- 25595685
TI  - 1,2,3,9b-Tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of
      respiratory syncytial virus (RSV) fusion inhibitors. Part 2: identification of
      BTA9881 as a preclinical candidate.
AB  - Respiratory syncytial virus (RSV) is a major cause of respiratory tract
      infections in infants, young children and adults. 1,2,3,9b-Tetrahydro-5H
      imidazo[2,1-a]isoindol-5-ones with general structure 1 were previously identified
      as promising inhibitors of RSV targeting the fusion glycoprotein. In particular,
      the introduction of a nitrogen at the 8-position of the tricyclic core yielded
      lead compounds 2 and 3. Extensive exploration of the R(2) group established that
      certain heterocyclic amides conferred potent RSV A&B activity and a good balance
      of physicochemical and pharmacokinetic properties. The antiviral activity was
      found to reside in a single enantiomer and compound 33a, (9bS)-9b-(4
      chlorophenyl)-1-(pyridin-3-ylcarbonyl)-1,2,3,9b-tetrahydro-5H
      imidazo[1',2':1,2]pyrrolo[3,4-c]pyridin-5-one (known as BTA9881), was identified
      as a candidate for preclinical development. 

PMID- 25595687
TI  - Proposition of a protocol to evaluate upper-extremity functional deficits and
      compensation mechanisms: application to elbow contracture.
AB  - OBJECTIVE: Instrumented gait analysis is widely accepted as an objective
      assessment of lower-extremity function. Conversely, upper-extremity function
      suffers from lack of objective evaluation. The present paper aims at proposing a
      protocol to be used to clinically and objectively evaluate upper-extremity
      function whatever the pathological joint. Secondly, it aims at better
      understanding the consequences on upper-extremity function and the compensation
      mechanisms induced by elbow contracture. Elbow contracture was simulated in this
      study by using a brace. DESIGN: Twelve healthy subjects followed an instrumented
      3D movement analysis while performing 11 daily life movements. The movements were
      performed with 3 different elbow contracture conditions, simulated by wearing an
      adjustable elbow brace. RESULTS: The proposed protocol was successful in creating
      a wide range of motion at all the upper-extremity joints. The activity-related
      range of motion and the mean range of motion computed on the whole set of daily
      life movements were effective in evaluating the severity of elbow contracture.
      The lack of elbow flexion was compensated by trunk flexion, hand flexion and
      radial deviation, and combined movement of shoulder flexion, abduction, and
      humeral internal rotation. Deficit in elbow extension was mainly compensated by
      the use of trunk flexion. CONCLUSION: A protocol could be proposed for the
      objective evaluation of upper-extremity function. Its application to elbow
      contracture suggests that loss of elbow flexion affects more movements than loss
      of elbow extension.

PMID- 25595686
TI  - Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that
      mimic 4-phenylbutyric acid.
AB  - The chemical chaperone 4-phenylbutyric acid (4-PBA) has potential as an agent for
      the treatment of neurodegenerative diseases. However, the requirement of high
      concentrations warrants chemical optimization for clinical use. In this study,
      novel naphthalene derivatives with a greater chemical chaperone activity than 4
      PBA were synthesized with analogy to the benzene ring. All novel compounds showed
      chemical chaperone activity, and 2 and 5 possessed high activity. In subsequent
      experiments, the protective effects of the compounds were examined in Parkinson's
      disease model cells, and low toxicity of 9 and 11 was related to amphiphilic
      substitution with naphthalene. 

PMID- 25595688
TI  - Role of asymptomatic carriers and weather variables in persistent transmission of
      malaria in an endemic district of Assam, India.
AB  - BACKGROUND: Malaria transmission is perennial in the Assam-Arunachal Pradesh
      interstate border areas in the Sonitpur district of Assam, India. A yearlong
      study was carried out on the incidence of symptomatic and asymptomatic malaria
      and the role of asymptomatic malaria carriers in persistent transmission of the
      disease. The relationships between malaria incidence and weather parameters were
      also investigated. METHODS: Active and mass blood surveys were conducted on a
      monthly basis in Bengenajuli, Sapairaumari Pathar, and Nigam villages near the
      Assam-Arunachal Pradesh border. Epidemiological indices were estimated for
      malaria-positive cases. Multiple linear regression between monthly malaria
      incidence and monthly average temperature, and relative humidity along with
      monthly total rainfall was carried out. The known malaria vectors collected in
      CDC light traps were identified and recorded. RESULTS: Slide positivity rate
      (SPR) and Plasmodium falciparum percent (Pf%) for symptomatic malaria were 26.1
      and 79.8, respectively. Prevalence of malaria vectors was observed throughout the
      year with varying density. Anopheles philippinensis/nivipes and A. annularis were
      predominant among the seven known vector species recorded currently. Asymptomatic
      parasitemia was detected throughout the year with SPR ranging from 4.8 to 5.3.
      Monthly rainfall with 1-month lag had the highest correlation (r=0.92) with SPR.
      The relationship between SPR and weather factors was established as SPR=
      114.22+0.58 Tmin+1.38 RH+0.03 RF (R2=0.89; p=0.00). CONCLUSION: Low and
      relatively constant levels of asymptomatic parasitemia was present in the study
      area. High malaria vector density and presence of asymptomatic malaria parasite
      carriers were responsible for persistent malaria transmission in the region. This
      study concludes that passive detection and prompt treatment of asymptomatic
      carriers is essential for preventing persistent disease transmission. Rainfall
      along with some other weather variables may be used for predicting the malaria
      epidemics in the region. The predictive information could be useful to target
      resources more effectively.

PMID- 25595689
TI  - Do open garbage dumps play a role in canine rabies transmission in Biyem-Assi
      health district in Cameroon?
AB  - BACKGROUND: Rabies is a neglected enzootic disease which represents a serious
      public health problem. In Cameroon, efforts to prevent human deaths caused by
      rabies are often thwarted by the lack of community awareness. The community
      knowledge, as well as attitudes and perception on rabies, is therefore important
      for both prevention of human deaths and control in animals. METHODS: A cross
      sectional study was carried out to evaluate the level of community knowledge as
      well as the role of open garbage dumps (OGDs) in the epidemiology of human
      rabies. Overall 420 heads of household were interviewed in the Biyem-Assi health
      district of Yaounde. OGDs were identified through a systematic check, and
      household wastes they contained were characterized. RESULTS: Although 66.9% of
      respondents have knowledge on stray dogs, only 35% of respondents knew the role
      of OGDs in the increase of stray dog population. Overall OGDs consisted of
      fermentable wastes. Nutrition places for stray dogs were wild garbage dumps
      (68.1%), markets (18.3%), and houses (13.6%). The feeding behavior of stray dogs
      correlated significantly with the human rabies transmission (chi (2)=154.12,
      df=4, p<0.05). CONCLUSION: Most participants knew that rabies could be
      transmitted by a dog bite as well as the measures to be taken in this type of
      situation. Increased knowledge of respondents on rabies showed OGDs and stray
      dogs as significant risk factors for canine rabies in Biyem-Assi health district.

PMID- 25595690
TI  - [Polio, the long walk to the endgame].
AB  - Although the WHO original target date for the global eradication of poliomyelitis
      was the year 2000 -thanks to vaccination and institutional, public and private,
      resources for that purpose-, in 2013 the disease remained endemic in three
      countries, Afghanistan, Pakistan and Nigeria, and some cases were described in
      five others. The circulation of wild type 1 poliovirus in Israel, Gaza and the
      West Bank and the cases in Syria were a wakeup call, as at that time there were
      polioviruses derived from the oral vaccine that are still circulating among the
      human population and can cause the development of the disease. Travelling "from"
      and "to" endemic areas are factors to consider in poliovirus exportation and in
      its spread when it reaches areas with poor immunogenicity. Wars, terrorism,
      intolerance, lack of culture and proliferation of anti-vaccine groups and the
      rise of the anti-vaccination movement are important factors in the maintenance
      and expansion of the virus and in the "non-vaccination" against it. Based on the
      international situation to date, the Emergency Committee of WHO met in May 2014
      to address the problem. It is still necessary to enhance the knowledge of the
      disease and its agent. In the first case to perform a differential diagnosis of
      flaccid paralysis and to continue vaccination programs, and in the second case to
      keep studying and looking for the poliovirus in environmental samples, which is a
      model for the study of many other viruses.

PMID- 25595691
TI  - Does Double-Bundle Anterior Cruciate Ligament Reconstruction Improve
      Postoperative Knee Stability Compared With Single-Bundle Techniques? A Systematic
      Review of Overlapping Meta-analyses.
AB  - PURPOSE: Multiple meta-analyses of randomized controlled trials, the highest
      available level of evidence, have been conducted to determine whether double
      bundle (DB) or single-bundle (SB) anterior cruciate ligament reconstruction (ACL
      R) provides superior clinical outcomes and knee stability; however, results are
      discordant. The purpose of this study was to conduct a systematic review of meta
      analyses comparing SB and DB ACL-R to discern the cause of the discordance and to
      determine which of these meta-analyses provides the current best available
      evidence. METHODS: We evaluated available scientific support for SB as compared
      with DB ACL-R by systematically reviewing the literature for published meta
      analyses. Data on patient clinical outcomes and knee stability (as measured by KT
      arthrometry and pivot-shift testing) were extracted. Meta-analysis quality was
      judged using the Oxman-Guyatt and Quality of Reporting of Meta-analyses systems.
      The Jadad algorithm was then applied to determine which meta-analyses provided
      the highest level of evidence. RESULTS: Nine meta-analyses were included, of
      which 3 included Level I Evidence and 6 included both Level I and Level II
      Evidence. Most studies found significant differences favoring DB reconstruction
      on pivot-shift testing, KT arthrometry measurement of anterior tibial
      translation, and International Knee Documentation Committee objective grading.
      Most studies detected no significant differences between the 2 techniques in
      subjective outcome scores (Tegner, Lysholm, and International Knee Documentation
      Committee subjective), graft failure, or complications. Oxman-Guyatt and Quality
      of Reporting of Meta-analyses scores varied, with 2 studies exhibiting major
      flaws (Oxman-Guyatt score <3). After application of the Jadad decision algorithm,
      3 concordant high-quality meta-analyses were selected, with each concluding that
      DB ACL-R provided significantly better knee stability (by KT arthrometry and
      pivot-shift testing) than SB ACL-R but no advantages in clinical outcomes or risk
      of graft failure. CONCLUSIONS: The current best available evidence suggests that
      DB ACL-R provides better postoperative knee stability than SB ACL-R, whereas
      clinical outcomes and risk of graft failure are similar between techniques. LEVEL
      OF EVIDENCE: Level II, systematic review of Level I and II studies.

PMID- 25595692
TI  - Meniscal allograft transplantation: how should we be doing it? A systematic
      review.
AB  - PURPOSE: We undertook a systematic review to assess a number of the technical
      aspects of meniscal allograft transplantation (MAT) that have not been covered in
      other reviews. Specific variables studied included the indications for MAT, graft
      fixation method, rehabilitation protocols, outcome scores, and definition of
      failure. METHODS: We performed a systematic literature review of the PubMed,
      EMBASE, and Cochrane databases to determine the outcomes of meniscal
      transplantation at greater than 2 years postoperatively. PRISMA (Preferred
      Reporting for Systematic Reviews and Meta-Analyses) guidelines were followed with
      a PRISMA checklist. The search was completed on January 5, 2014. RESULTS: These
      queries returned 629 results from which 41 articles were identified as meeting
      the inclusion criteria. No studies in this review were randomized or controlled.
      CONCLUSIONS: MAT is a worthwhile procedure, with evidence that it provides pain
      relief and improved function, and good results reported in mid- to long-term
      studies. The procedure should be considered only in a patient with localized pain
      and a stable (or stabilized) and well-aligned (or realigned) knee. The
      controversial areas studied in this review include the following: there is no
      evidence to support fixation with either bone plugs or soft tissue; there is no
      standardized rehabilitation program, but it appears that full weight bearing by 6
      weeks is not detrimental; and a clear and uniform definition of failure and use
      of consistent outcome scores would aid future reporting and analysis of the
      results of meniscal transplantation. LEVEL OF EVIDENCE: Level IV, systematic
      review of Level II to IV studies.

PMID- 25595693
TI  - Resorbable collagen scaffolds for the treatment of meniscus defects: a systematic
      review.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and structural
      outcomes after resorbable collagen meniscus scaffold implantation through a
      systematic review of the published literature. METHODS: A systematic search of
      both the PubMed and Embase databases was undertaken to identify all studies that
      reported clinical and/or structural outcomes after resorbable collagen meniscus
      scaffold implantation for the treatment of defects involving either the medial or
      lateral meniscus. Extracted data included study characteristics; surgical methods
      and rehabilitation protocols; objective outcomes; and preoperative and
      postoperative subjective outcome scores including Lysholm, Tegner, International
      Knee Documentation Committee, and visual analog scale scores. RESULTS: Thirteen
      studies were included in this review. There were 10 Level IV studies, 2 Level II
      studies, and 1 Level I study with follow-up intervals ranging from 3 months to
      12.5 years. With a few exceptions, the study designs used in each study generally
      followed those which had been previously performed. Substantial differences in
      rehabilitation protocols and concomitant procedures were noted that may have had
      an effect on overall clinical outcomes. Objective findings were mostly consistent
      and typically showed minimal degenerative changes on postoperative radiographs,
      decreased signal intensity of the scaffold over time on magnetic resonance
      imaging, the presence of meniscus-like tissue at second-look arthroscopy, and
      good integration of new tissue as evidenced by histologic analysis of biopsy
      specimens. Most studies reported satisfactory clinical outcomes, and most
      patients showed substantial improvements in comparison with mean preoperative
      baseline values. CONCLUSIONS: On the basis of this systematic review,
      implantation of resorbable collagen scaffolds for the treatment of meniscus
      defects provides satisfactory clinical and structural outcomes in most cases.
      There is evidence that collagen meniscus scaffold implantation provides superior
      clinical outcomes when compared with partial meniscectomy alone. LEVEL OF
      EVIDENCE: Level IV, systematic review of Level I, II, and IV studies.

PMID- 25595695
TI  - Bone grafts and bone substitutes for opening-wedge osteotomies of the knee: a
      systematic review.
AB  - PURPOSE: To establish the rate of use of various void fillers in the setting of
      opening-wedge osteotomy around the knee, the types of fixation used, and the
      rates of delayed union or nonunion related to these variables. In addition, this
      review addressed short-term to midterm outcomes and complication rates associated
      with such procedures. METHODS: The electronic databases Medline, Embase, and
      PubMed were searched using the methodology for systematic review as recommended
      by the Cochrane Collaboration. The search terms used were as follows: knee,
      osteotomy, knee joint, bone grafting, opening osteotomy, opening wedge, tibial
      osteotomy, femoral osteotomy, and bone substitute. We screened 1,383 articles and
      applied exclusion criteria. Fifty-six articles were included. RESULTS: We
      included 3,033 cases of osteotomy in 2,910 patients. The mean age of patients was
      50 years, with a mean follow-up period of 42 months. Male patients comprised 52%
      of patients. The mean alignment change was 10.8 degrees , shifting the mechanical
      axis to 5.1 degrees  valgus. Delayed union/nonunion rates were 2.6%, 4.6%, and
      4.5% for autograft, allograft bone, and synthetic bone substitutes, respectively
      (P = .03). Delayed union/nonunion rates were significantly lower for autograft
      compared with allograft (P = .03) and for autograft and allograft compared with
      synthetic bone substitutes (P < .0001). Non-locking plates (n = 2,148) had a rate
      of delayed union/nonunion of 3.7% and a mean loss of correction over time of 0.5
      degrees . Locking plates (n = 681) had a rate of delayed union/nonunion of 2.6%
      and a loss of correction of 2.3 degrees . All mean knee outcome scores improved,
      and an overall complication rate of 14% was found. CONCLUSIONS: Opening-wedge
      osteotomy had good short-term to midterm outcomes with acceptable complication
      rates. The lowest rates of delayed union/nonunion were in autograft bone-filled
      osteotomies. Plate type does not appear to affect osteotomy union or loss of
      correction. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV
      studies.

PMID- 25595694
TI  - Bio-enhanced repair of the anterior cruciate ligament.
AB  - Suture repair of the anterior cruciate ligament (ACL) has been widely abandoned
      in favor of ACL reconstruction, largely because of the high rates of failure and
      unreliability of the outcomes after suture repair. However, there have been
      recent basic science studies that suggest that combining a suture repair with a
      biological adjunct may improve the results of suture repair of the ACL, with
      several studies in large animal models showing equivalent strength of an ACL
      treated with bio-enhanced repaired to that of an ACL graft at 3, 6, and 12 months
      after surgery. In addition, the groups treated with bio-enhanced repair had
      significantly less osteoarthritis when compared with the animals undergoing ACL
      reconstruction. These findings have led to a renewed interest in bio-enhanced
      primary repair as a way to make repair of the ACL a viable option for a select
      group of patients in the future. 

PMID- 25595696
TI  - Platelet-rich plasma use in anterior cruciate ligament surgery: systematic review
      of the literature.
AB  - PURPOSE: To systematically review the current literature for evidence that would
      substantiate the use of platelet-rich plasma (PRP) in the treatment of anterior
      cruciate ligament (ACL) ruptures. METHODS: We performed a systematic search in
      PubMed and Embase of studies written in the English and Spanish languages that
      compared the use of PRP with a control group in patients with ACL injuries
      assessing graft-to-bone healing, graft maturation, and/or clinical outcomes and
      were randomized controlled trials or prospective cohort studies. RESULTS: Eleven
      studies fulfilled the inclusion criteria, comprising 516 patients (266 ACL
      reconstructions using PRP and 250 ACL reconstructions without PRP). Six studies
      reported a statistically significant difference (4 studies) or tendency toward
      faster graft maturation in the platelet group (2 studies). One study found no
      differences. Regarding tunnel healing/widening, 1 study showed faster healing in
      the PRP group and 5 studies showed no differences between the 2 groups.
      Considering clinical outcomes, 1 study showed better clinical outcomes with PRP
      use and 5 studies showed no benefits with the use of PRP. CONCLUSIONS: Concerning
      ACL graft maturation, there is promising evidence that the addition of PRP could
      be a synergic factor in acquiring maturity more quickly than grafts with no PRP,
      with the clinical implication of this remaining unclear. Regarding tunnel
      healing, it appears that there is not an improvement with the addition of PRP.
      There is no proof that clinical outcomes of ACL surgery are enhanced by the use
      of PRP. LEVEL OF EVIDENCE: Level III, systematic review of Level I through III
      studies.

PMID- 25595697
TI  - Familial effects on structural changes relevant to knee osteoarthritis: a
      prospective cohort study.
AB  - OBJECTIVE: Genetic factors play an important role in the pathogenesis of knee
      osteoarthritis (OA), but which knee structural changes mediate this is unclear.
      This study aimed to describe the differences in knee structural changes over 8-10
      years between offspring having at least one parent with total knee replacement
      (TKR) for severe primary knee OA and controls with no family history of knee OA.
      DESIGN: 115 offspring (mean age 45 years) with a family history of TKR for severe
      knee OA were compared with 104 (mean age 46 years) controls. T1 or T2-weighted
      fat saturated magnetic resonance imaging (MRI) was performed respectively to
      evaluate knee cartilage defects, bone marrow lesions (BMLs), meniscal extrusion
      and tears at baseline and 10 years. Multivariate logistic regression model was
      used to adjust for potential confounders. RESULTS: Offspring had a greater
      increase in cartilage defect score (1.03 vs 0.52, P = 0.007) and meniscal
      extrusion score (0.28 vs 0.10, P = 0.027) over 10 years, and a greater increase
      in meniscal tear score (0.40 vs 0.10, P = 0.012) over 8 years in the medial but
      not the lateral tibiofemoral compartment. Changes in BMLs over 8-years were not
      different between the two groups. These associations were independent of
      potential confounders, and strengthened after further adjustment for each other.
      CONCLUSION: With the exception of BMLs, offspring with a family history of knee
      OA have a greater risk of increases in multiple knee structural abnormalities in
      the medial tibiofemoral compartment suggesting pleiotropic familial effects.

PMID- 25595698
TI  - A new prescription for growth? Statins, cholesterol and cartilage homeostasis.

PMID- 25595699
TI  - Posaconazole: a review of the gastro-resistant tablet and intravenous solution in
      invasive fungal infections.
AB  - Posaconazole (Noxafil((r))) is a triazole antifungal agent with an extended
      spectrum of antifungal activity. It is approved for the prophylaxis of invasive
      fungal infections in patients with neutropenia or in haematopoietic stem cell
      transplant recipients undergoing high-dose immunosuppressive therapy for graft
      versus-host disease, and for the treatment of fungal infections. The efficacy and
      good tolerability of posaconazole oral suspension administered three or four
      times daily is well established. However, in order to overcome pharmacokinetic
      limitations associated with the suspension, a new gastro-resistant tablet and
      intravenous (IV) solution were developed. This article reviews the
      pharmacokinetic properties of the new posaconazole formulations and briefly
      summarizes efficacy data relating to the suspension. The pharmacokinetic
      advantages of the posaconazole gastro-resistant tablet compared with the
      suspension formulation include less interpatient variability, better systemic
      availability enabling once-daily administration, and absorption that is
      unaffected by changes in gastric pH or motility; in addition the tablets may be
      taken with or without food. The posaconazole tablet achieves higher and more
      consistent mean plasma concentrations than the suspension and, therefore, it is
      the preferred option to optimize efficacy in the prophylaxis or treatment of
      invasive fungal disease. The posaconazole IV solution provides an option for
      these same indications in patients who are unable to receive oral formulations. 

PMID- 25595701
TI  - Discontinuing inhaled steroids might not be safe in severe COPD cases.

PMID- 25595700
TI  - Dietary supplementation with arachidonic acid increases arachidonic acid content
      in paw, but does not affect arthritis severity or prostaglandin E2 content in rat
      adjuvant-induced arthritis model.
AB  - BACKGROUND: Arachidonic acid (ARA) is an essential fatty acid and a major
      constituent of biomembranes. It is converted into various lipid mediators, such
      as prostaglandin E2 (PGE2), which is involved in the development of rheumatoid
      arthritis (RA). However, the effects of dietary ARA on RA are unclear. Our
      objective was to clarify the effects of dietary ARA on an experimental rat
      arthritis model. METHODS: Lew rats were fed three contents of ARA diet (0.07%,
      0.15% or 0.32% ARA in diet (w/w)), a docosahexaenoic acid (DHA) diet (0.32% DHA),
      or a control diet. After 4 weeks, arthritis was induced by injection of Freund's
      complete adjuvant into the hind footpad. We observed the development of arthritis
      for another 4 weeks, and evaluated arthritis severity, fatty acid and lipid
      mediator contents in the paw, and expression of genes related to lipid mediator
      formation and inflammatory cytokines. Treatment with indomethacin was also
      evaluated. RESULTS: The ARA content of phospholipids in the paw was significantly
      elevated with dietary ARA in a dose-dependent manner. Dietary ARA as well as DHA
      did not affect arthritis severity (paw edema, arthritis score, and bone erosion).
      PGE2 content in the paw was increased by arthritis induction, but was not
      modified by dietary ARA. Dietary ARA did not affect the contents of other lipid
      mediators and gene expression of cyclooxygenase (COX)-1, COX-2, lipoxgenases and
      inflammatory cytokines. Indomethacin suppressed arthritis severity and PGE2
      content in the paw. CONCLUSION: These results suggest that dietary ARA increases
      ARA content in the paw, but has no effect on arthritis severity and PGE2 content
      of the paw in a rat arthritis model.

PMID- 25595703
TI  - One of the most frequently encountered clinical issues in primary care medicine
      is that of urinary tract infections. Foreword.

PMID- 25595702
TI  - Performance of the ActiGraph accelerometer using a national population-based
      sample of youth and adults.
AB  - BACKGROUND: Accelerometer output may be semi-continuous or continuous in nature,
      which has implications on discerning non-wear and defining physical activity
      intensity levels. This study described field-based accelerometer performance from
      a surveillance sample of youth and adults. METHODS: Using 2003-2006 National
      Health and Nutrition Examination Survey data, 4,028 youth ages 6 to 17 years and
      7,931 adults age > =18 years wore an ActiGraph AM7164 accelerometer for one week,
      providing at least 3 days of wear for > =8 hours/day. Accelerometer performance
      was assessed by exploring the number of different values of accelerometer
      counts/minute for each participant. RESULTS: On average, youth participants had
      1381 different counts/minute over 7 days (median 1360, interquartile range 1127
      1623) and adult participants had 1101 different counts/minute over 7 days (median
      1085, interquartile range 874-1313). For both youth and adults, when restricting
      to counts/minute between 0 to 4999, every possible value (in counts/minute)
      occurred at least once. CONCLUSION: The field-based data confirmed that the
      accelerometer used in this study allowed for continuous counts/minute through
      which all but the most vigorous activities would usually occur.

PMID- 25595704
TI  - Influence of impulsiveness on emotional modulation of response inhibition: An ERP
      study.
AB  - OBJECTIVE: To examine how impulsiveness influences the emotional modulation of
      behavioral and neural correlates of response inhibition. METHODS: Twenty-nine
      healthy individuals scoring high (HI, N=16) or low (LI, N=13) on motor
      impulsiveness performed an emotional Go/Nogo task, including the presentation of
      pleasant, neutral and unpleasant pictures. Behavioral [reaction times (RTs),
      accuracy to Go and Nogo trials] and neural (Nogo-N2 and Nogo-P3) correlates of
      response inhibition were compared between HI and LI groups. RESULTS: Larger Nogo
      P3 was found for emotional than neutral stimuli in HI relative to LI group.
      Faster RTs to Go stimuli and lower accuracy to Nogo stimuli were correlated with
      larger Nogo-P3 in HI, but not LI, group. No significant interactions between
      emotion content and impulsiveness for Nogo-N2 and behavioral measures were noted.
      CONCLUSIONS: Impulsiveness influences the emotional modulation of response
      inhibition by potentiating the response tendencies evoked by the emotional
      stimuli. Accordingly, high impulsive individuals may need an increased and/or
      more effortful response inhibition in order to counteract the prepotent tendency
      to respond elicited by the combination of high trait impulsiveness and high
      emotional arousal. SIGNIFICANCE: The present study suggests the importance to
      examine how pathological impulsiveness may interact with emotional arousal in
      modulating response inhibition.

PMID- 25595705
TI  - Response to a Letter to the Editor by Joachim Denner on HIV infection en route to
      endogenization: two cases.

PMID- 25595706
TI  - Current epidemiology and antimicrobial resistance data for bacterial bloodstream
      infections in patients with hematologic malignancies: an Italian multicentre
      prospective survey.
AB  - A prospective cohort study was conducted in nine hematology wards at tertiary
      care centres or at university hospitals located throughout Italy from January
      2009 to December 2012. All of the cases of bacterial bloodstream infection (BBSI)
      occurring in adult patients with hematologic malignancies were included. A total
      of 668 bacterial isolates were recovered in 575 BBSI episodes. Overall, the
      susceptibility rates of Gram-negative bacteria were 59.1% to ceftazidime, 20.1%
      to ciprofloxacin, 79.1% to meropenem, 85.2% to amikacin, 69.2% to gentamicin and
      69.8% to piperacillin/tazobactam. Resistance to third-generation cephalosporins
      was found in 98/265 (36.9%) of Enterobacteriaceae isolates. Among Klebsiella
      pneumoniae strains, 15/43 (34.9%) were resistant to carbapenems. Of 66
      Pseudomonas aeruginosa isolates, 46 (69.7%) were multidrug resistant. Overall,
      the susceptibility rates of Gram-positive bacteria were 97.4% to vancomycin and
      94.2% to teicoplanin. Among the monomicrobial cases of BBSI, the 21-day mortality
      rate was significantly higher for those caused by Gram-negative bacteria compared
      to those caused by Gram-positive bacteria (47/278, 16.9% vs. 12/212, 5.6%; p <
      0.001). Among Gram-negative bacteria, the mortality rate was significantly higher
      for BBSI caused by K. pneumoniae, P. aeruginosa, and Acinetobacter baumannii. Our
      results confirm the recently reported shift of prevalence from Gram-positive to
      Gram-negative bacteria as causative agents of BBSIs among patients with
      hematologic malignancies and highlight a worrisome increasing frequency in
      antimicrobial resistance among Gram-negative bacteria.

PMID- 25595707
TI  - Genetic diversity of Mycobacterium tuberculosis isolates from foreign-born and
      Japan-born residents in Tokyo.
AB  - Sequences of the full genomes of 259 clinical isolates of Mycobacterium
      tuberculosis, obtained from foreign-born and Japan-born patients in Tokyo, Japan,
      were determined, and a phylogenetic tree constructed by concatenated single
      nucleotide polymorphism (SNP) sequences. The 259 isolates were clustered into
      four clades: Lineage 2 (East Asian or "Beijing" genotype; n = 182, 70.3%),
      Lineage 4 (Euro-American, n = 46, 17.8%), Lineage 1 (Indo-Oceanic, n = 23, 8.9%),
      and Lineage 3 (East African-Indian, n = 8, 3.1%). Of the 259, 36 (13.9%) were
      resistant to at least one drug. There was no multi-drug-resistant isolate. Drug
      resistance was greater for the strains in Lineage 2 than the non-Lineage 2. The
      proportion of Lineage 2 isolates was significantly smaller in foreign-born (n =
      43/91, 47.3%) than in Japan-born (n = 139/168, 82.7%) patients, whereas the
      proportion of Lineage 1 isolates was significantly larger in foreign-born (n =
      19/91, 20.9%) than in Japan-born (n = 4/168, 2.4%) patients. We also found eight
      SNPs specific to the typical Beijing sub-genotype in Lineage 2, including 4 non
      synonymous SNPs. Of the 259 isolates, 244 had strain-specific SNP(s) and small (1
      30-bp) insertions and deletions (indels). The numbers of strain-specific SNPs and
      indels per isolate were significantly larger from foreign-born (median 89, range
      0-520) than from Japan-born (median 23, range 0-415) (p 3.66E-15) patients. These
      results suggested that M. tuberculosis isolates from foreign-born patients had
      more genetic diversity than those from Japan-born patients.

PMID- 25595710
TI  - The relationship between macroeconomic and industry-specific business cycle
      indicators and work-related injuries among Danish construction workers.
AB  - OBJECTIVES: The current study examines and compares the relationship between both
      macroeconomic and industry-specific business cycle indicators, and work-related
      injuries among construction workers in Denmark using emergency department (ED)
      injury data and also officially reported injuries to the Danish Working
      Environment Authority (WEA). METHODS: The correlations between ED and WEA injury
      data from the catchment area of Odense University Hospital during the period 1984
      2010 were tested separately for variability and trend with two general
      macroeconomic indicators (gross domestic product and the Danish unemployment
      rate) and two construction industry-specific indicators (gross value added and
      the number of employees). RESULTS: The results show that injury rates increase
      during economic booms and decrease during recessions. However, the regression
      coefficients were generally weak for both the ED (range 0.14-0.20) and WEA
      injuries (range 0.13-0.36). Furthermore, although there is some variability in
      the strength of the relationship of the different business cycle indicators, the
      relationships are generally not stronger for the WEA injuries than for the ED
      injuries, except for general unemployment. Similarly, no substantial differences
      in strength of relation between industry-specific and macroeconomic indicators
      were identified. CONCLUSIONS: The study shows that there was no difference in the
      relationship between business cycle indicators, and WEA and ED injury data. This
      indicates that changes in reporting behaviour do not seem to play a major role in
      the relation between the business cycle and workplace injuries in a Danish
      context.

PMID- 25595708
TI  - Use of efavirenz or atazanavir/ritonavir is associated with better clinical
      outcomes of HAART compared to other protease inhibitors: routine evidence from
      the Italian MASTER Cohort.
AB  - Randomized trials and observational cohorts reported higher rates of virological
      suppression after highly active antiretroviral therapy (HAART) including
      efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations
      with immunological and clinical outcomes are unclear. Patients of the Italian
      MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding
      outcome (composite outcome for success (COS)) was introduced. We evaluated
      predictors of COS (no AIDS plus CD4+ count >500/mm(3)plus HIV-RNA <500 copies/mL)
      and of eight single outcomes either at month 6 or at year 3. Multivariable
      logistic regression was conducted. There were 6259 patients selected. Patients on
      EFV (43%) were younger, had greater CD4+ count, presented with AIDS less
      frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500
      copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs
      achieved COS (p <0.0001). At multivariable analysis, patients on
      lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001).
      Foreign origin and positive hepatitis C virus-Ab were independently associated
      with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively).
      Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8%
      vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths
      of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study,
      naive patients on EFV performed better than those on boosted PIs after adjustment
      for imbalances at baseline. Even when virological control is achieved, COS is
      relatively rare. Hepatitis C virus-positive patients and those of foreign origin
      are at risk of not obtaining COS. 

PMID- 25595711
TI  - Patterns of HIV, TB, and non-communicable disease multi-morbidity in peri-urban
      South Africa- a cross sectional study.
AB  - BACKGROUND: Many low and middle-income countries are experiencing colliding
      epidemics of chronic infectious (ID) and non-communicable diseases (NCD). As a
      result, the prevalence of multiple morbidities (MM) is rising. METHODS: We
      conducted a study to describe the epidemiology of MM in a primary care clinic in
      Khayelitsha. Adults with at least one of HIV, tuberculosis (TB), diabetes (DM),
      and hypertension (HPT) were identified between Sept 2012-May 2013 on electronic
      databases. Using unique patient identifiers, drugs prescribed across all
      facilities in the province were linked to each patient and each drug class
      assigned a condition. RESULTS: These 4 diseases accounted for 45% of all
      prescription visits. Among 14364 chronic disease patients, HPT was the most
      common morbidity (65%). 22.6% of patients had MM, with an increasing prevalence
      with age; and a high prevalence among younger antiretroviral therapy (ART)
      patients (26% and 30% in 18-35 yr and 36-45 year age groups respectively). Among
      these younger ART patients with MM, HPT and DM prevalence was higher than in
      those not on ART. CONCLUSIONS: We highlight the co-existence of multiple ID and
      NCD. This presents both challenges (increasing complexity and the impact on
      health services, providers and patients), and opportunities for chronic diseases
      screening in a population linked to care. It also necessitates re-thinking of
      models of health care delivery and requires policy interventions to integrate and
      coordinate management of co-morbid chronic diseases.

PMID- 25595712
TI  - Three dimensional spheroid cell culture for nanoparticle safety testing.
AB  - Nanoparticles are widely employed for many applications and the number of
      consumer products, incorporating nanotechnology, is constantly increasing. A
      novel area of nanotechnology is the application in medical implants. The
      widespread use of nanoparticles leads to their higher prevalence in our
      environment. This, in turn, raises concerns regarding potential risks to humans.
      Previous studies have shown possible hazardous effects of some nanoparticles on
      mammalian cells grown in two-dimensional (2D) cultures. However, 2D in vitro cell
      cultures display several disadvantages such as changes in cell shape, cell
      function, cell responses and lack of cell-cell contacts. For this reason, the
      development of better models for mimicking in vivo conditions is essential. In
      the present work, we cultivated A549 cells and NIH-3T3 cells in three-dimensional
      (3D) spheroids and investigated the effects of zinc oxide (ZnO-NP) and titanium
      dioxide nanoparticles (TiO2-NP). The results were compared to cultivation in 2D
      monolayer culture. A549 cells in 3D cell culture formed loose aggregates which
      were more sensitive to the toxicity of ZnO-NP in comparison to cells grown in 2D
      monolayers. In contrast, NIH-3T3 cells showed a compact 3D spheroid structure and
      no differences in the sensitivity of the NIH-3T3 cells to ZnO-NP were observed
      between 2D and 3D cultures. TiO2-NP were non-toxic in 2D cultures but affected
      cell-cell interaction during 3D spheroid formation of A549 and NIH-3T3 cells.
      When TiO2-NP were directly added during spheroid formation in the cultures of the
      two cell lines tested, several smaller spheroids were formed instead of a single
      spheroid. This effect was not observed if the nanoparticles were added after
      spheroid formation. In this case, a slight decrease in cell viability was
      determined only for A549 3D spheroids. The obtained results demonstrate the
      importance of 3D cell culture studies for nanoparticle safety testing, since some
      effects cannot be revealed in 2D cell culture. 

PMID- 25595713
TI  - Phosphatidylcholine and the intestinal mucus layer: in vitro efficacy against
      Clostridium difficile-associated polymorphonuclear neutrophil activation.
AB  - BACKGROUND: Phosphatidylcholine (PC), an important component of intestinal mucus,
      protects against Clostridium difficile toxin-induced intestinal barrier injury in
      vitro. Polymorphonuclear neutrophil (PMN) activation may contribute to intestinal
      injury and systemic toxicity in patients with C. difficile-associated disease. We
      therefore hypothesized that the intestinal barrier function against C. difficile
      toxin by exogenous PC would ameliorate PMN activation. METHODS: Intestinal
      epithelial cell (IEC) monolayers were cocultured with C. difficile toxin A and/or
      exogenous PC. Naive PMNs were cocultured with IEC culture supernatants and PMN
      activation, and chemotactic potential determined. RESULTS: PC treatment of IEC
      abrogated the enhanced PMN activation and chemotactic potential following toxin A
      exposure (P < .001). CONCLUSIONS: Exogenous PC ameliorated PMN activation from
      IECs exposed to C. difficile toxin. Administration of exogenous PC may be a
      useful adjunctive treatment in severely ill or immunocompromised patients with C.
      difficile-associated disease.

PMID- 25595714
TI  - Low 24-hour urine calcium levels in patients with sporadic primary
      hyperparathyroidism: is further evaluation warranted prior to parathyroidectomy?
AB  - BACKGROUND: Low 24-hour urine calcium (uCa) levels in patients with primary
      hyperparathyroidism (pHPT) raise concern for familial hypocalciuric
      hypercalcemia. This study evaluated patients with a low 24-hour uCa level for
      potential differences that may guide the extent of preoperative evaluation
      needed. METHODS: A retrospective review was conducted of 1,139 sporadic pHPT
      patients who underwent parathyroidectomy between December 1999 and May 2011.
      RESULTS: Of the 54 (5%) patients with greater than or equal to one low 24-hour
      uCa (<100 mg), 28 (52%) patients had only one low level, 9 (17%) had multiple low
      levels, and 17 (31%) had a repeat 24-hour uCa greater than 100. In the latter
      group, 4 of the 9 (53%) patients were on a thiazide and had normalization after
      cessation. Among the groups, differences existed only in serum creatinine (P =
      .0011) and glomerular filtration rate (P = .0007). CONCLUSION: This study
      suggests that sporadic pHPT patients with low 24-hour uCa levels may not require
      further evaluation with genetic testing for familial hypocalciuric hypercalcemia,
      especially if previous eucalcemia is documented.

PMID- 25595715
TI  - RNAMotifScanX: a graph alignment approach for RNA structural motif
      identification.
AB  - RNA structural motifs are recurrent three-dimensional (3D) components found in
      the RNA architecture. These RNA structural motifs play important structural or
      functional roles and usually exhibit highly conserved 3D geometries and base
      interaction patterns. Analysis of the RNA 3D structures and elucidation of their
      molecular functions heavily rely on efficient and accurate identification of
      these motifs. However, efficient RNA structural motif search tools are lacking
      due to the high complexity of these motifs. In this work, we present
      RNAMotifScanX, a motif search tool based on a base-interaction graph alignment
      algorithm. This novel algorithm enables automatic identification of both
      partially and fully matched motif instances. RNAMotifScanX considers noncanonical
      base-pairing interactions, base-stacking interactions, and sequence conservation
      of the motifs, which leads to significantly improved sensitivity and specificity
      as compared with other state-of-the-art search tools. RNAMotifScanX also adopts a
      carefully designed branch-and-bound technique, which enables ultra-fast search of
      large kink-turn motifs against a 23S rRNA. The software package RNAMotifScanX is
      implemented using GNU C++, and is freely available from
      http://genome.ucf.edu/RNAMotifScanX. 

PMID- 25595717
TI  - Modern standards of ECG interpretation in young athletes: yield and
      effectiveness.
AB  - Although cardiovascular screening is recommended before participating in
      competitive sports, the role of the 12-lead electrocardiogram (ECG) has been
      debated. When added to the medical history and physical examination, an ECG used
      during the pre-participation screening (PPS) of young athletes can greatly
      enhance the ability to detect underlying cardiovascular pathology. Concerns over
      false positive rates, however, have posed an obstacle to large-scale
      implementation. The recent development of modern athlete-specific ECG
      interpretation criteria has dramatically reduced false positive rates to levels
      below other commonly used screening tests (e.g. breast cancer, prostate cancer)
      and subsequently improved cost effectiveness. There are also emerging data that
      certain sub-groups have a higher prevalence of ECG abnormalities, including
      males, athletes of Afro-Caribbean descent, basketball players, and endurance
      athletes. While false positive rates from a number of studies are reduced with
      the improved standards, there may be room for continued improvements. Future
      efforts should focus on refining criteria based on age, race, gender, ethnicity,
      and sport, while also clearly delineating the appropriate work-up strategies for
      those with abnormal findings, as this can lead to improved resource utilization.

PMID- 25595716
TI  - MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1alpha
      and PPARgamma.
AB  - In hepatitis B virus (HBV)-replicating hepatocytes, miR-130a expression was
      significantly reduced. In a reciprocal manner, miR-130a reduced HBV replication
      by targeting at two major metabolic regulators PGC1alpha and PPARgamma, both of
      which can potently stimulate HBV replication. We proposed a positive feed-forward
      loop between HBV, miR-130a, PPARgamma, and PGC1alpha. Accordingly, HBV can
      significantly enhance viral replication by reducing miR-130a and increasing
      PGC1alpha and PPARgamma. NF-kappaB/p65 can strongly stimulate miR-130a promoter,
      while miR-130a can promote NF-kappaB/p65 protein level by reducing PPARgamma and
      thus NF-kappaB/p65 protein degradation. We postulated another positive feed
      forward loop between miR-130a and NF-kappaB/p65 via PPARgamma. During liver
      inflammation, NF-kappaB signaling could contribute to viral clearance via its
      positive effect on miR-130a transcription. Conversely, in asymptomatic HBV
      carriers, persistent viral infection could reduce miR-130a and NF-kappaB
      expression, leading to dampened inflammation and immune tolerance. Finally, miR
      130a could contribute to metabolic homeostasis by dual targeting PGC1alpha and
      PPARgamma simultaneously. 

PMID- 25595718
TI  - Clinical meaning of isolated increase of QRS voltages in hypertrophic
      cardiomyopathy versus athlete's heart.
AB  - Recent consensus documents have provided modern criteria for interpretation of
      the athlete's ECG, which are based on a better definition of physiological versus
      abnormal ECG changes. The aim of these modern criteria is to lower the
      traditionally high number of false positives and to reduce unnecessary and
      expensive investigations, maintaining the sensitivity for identification of
      cardiac diseases at risk of sudden cardiac death during sports such as
      hypertrophic cardiomyopathy (HCM). This article reviews the published studies
      regarding the ECG changes associated with HCM ("pathologic hypertrophy") and
      athlete's heart ("physiologic hypertrophy"), with particular reference to the
      prevalence and clinical significance of the ECG pattern of isolated increase of
      QRS voltages. Taken together the results of the available studies show that ECG
      provides good accuracy for differentiating HCM from athlete's heart and allows to
      preserve the ECG power for detection of athletes with HCM. Patients with either
      completely normal ECGs or showing isolated QRS voltage criteria for LV
      hypertrophy have a less severe HCM phenotype, which is associated with a lower
      arrhythmic risk. These scientific data support the current recommendation that
      further cardiovascular tests including echocardiography are not systematically
      indicated in trained athletes showing an isolated increase of QRS voltages.

PMID- 25595719
TI  - Removing ventricular far-field signals in intracardiac electrograms during stable
      atrial tachycardia using the periodic component analysis.
AB  - BACKGROUND: Intracardiac electrograms are an indispensable part during diagnosis
      of supraventricular arrhythmias, but atrial activity (AA) can be obscured by
      ventricular far-fields (VFF). Concepts based on statistical independence like
      principal component analysis (PCA) cannot be applied for VFF removal during
      atrial tachycardia with stable conduction. METHODS: A database of realistic
      electrograms containing AA and VFF was generated. Both PCA and the new technique
      periodic component analysis (piCA) were implemented, benchmarked, and applied to
      clinical data. RESULTS: The concept of piCA was successfully verified to retain
      compromised AA morphology, showing high correlation (cc=0.98+/-0.01) for stable
      atrial cycle length (ACL). Performance of PCA failed during temporal coupling
      (cc=0.03+/-0.08) but improved for increasing conduction variability (cc=0.77+/
      0.14). Stability of ACL was identified as a critical parameter for piCA
      application. Analysis of clinical data confirmed these findings. CONCLUSION: piCA
      is introduced as a powerful new technique for artifact removal in periodic
      signals. Its concept and performance were benchmarked against PCA using simulated
      data and demonstrated on measured electrograms.

PMID- 25595720
TI  - Distinctive cutaneous and systemic features associated with antitranscriptional
      intermediary factor-1gamma antibodies in adults with dermatomyositis.
AB  - BACKGROUND: Antibodies against transcriptional intermediary factor (TIF)-1gamma
      are associated with malignancy in dermatomyositis (DM). Identification of
      clinical findings associated with anti-TIF-1gamma antibodies in DM is a high
      priority for both patient diagnosis and risk assessment. OBJECTIVE: We sought to
      define the clinical phenotype of patients with anti-TIF-1gamma DM. METHODS: Using
      a novel, sensitive, and specific assay for anti-TIF-1gamma antibodies, we
      retrospectively tested plasma from 134 adult patients with DM and examined
      associations between anti-TIF-1gamma antibodies and particular clinical and
      laboratory features. RESULTS: In all, 55 (41%) patients had autoantibodies to TIF
      1gamma. Anti-TIF-1gamma positive patients were less likely to have systemic
      features including interstitial lung disease, Raynaud phenomenon, and
      arthritis/arthralgia. Patients with TIF-1gamma autoantibodies had more extensive
      skin involvement, and some patients manifested characteristic findings including
      palmar hyperkeratotic papules, psoriasis-like lesions and a novel finding of
      hypopigmented and telangiectatic ("red on white") patches. LIMITATIONS: This was
      a retrospective study from a single tertiary referral center. CONCLUSION: TIF
      1gamma is the most commonly targeted DM-specific autoantigen in adults in a large
      US cohort. Although these patients tend to have less systemic involvement, their
      skin disease is often extensive and characteristic. Recognition of cutaneous
      findings in anti-TIF-1gamma positive patients may allow more accurate and timely
      diagnosis and effective treatment of patients with DM.

PMID- 25595721
TI  - Enhanced anti-cancer activity by curcumin-loaded hydrogel nanoparticle derived
      aggregates on A549 lung adenocarcinoma cells.
AB  - To investigate the anti-cancer activity of curcumin-loaded hydrogel nanoparticle
      derived aggregates on A549 lung adenocarcinoma cells. Curcumin was incorporated
      with biopolymeric chitosan, gelatin, and hyaluronan nanoparticles using an
      electrostatic field system. Characteristics of curcumin-loaded aggregates were
      examined including size and morphology, incorporation efficiency, stability and
      in vitro release. Treatment effect on A549 cells were assessed with cell
      viability assay, apoptosis assay, cell cycle analysis, reactive oxygen species
      detection, and Western blot. Observation from transmission electron microscopy
      show that the prepared biopolymeric nanoparticles were approximately 3-4 nm in
      diameter and that the size of the aggregates increased to approximately 26-55 nm
      after the incorporation of curcumin with the nanoparticles. The incorporation
      efficiency of curcumin into the chitosan, gelatin, and hyaluronan nanoparticles
      was 81, 67, and 78 % respectively. The formation of hyaluronan/curcumin and
      gelatin/curcumin aggregates seems to improve the stability of curcumin drug. The
      chitosan/curcumin aggregate has a faster release of curcumin than
      gelatin/curcumin and hyaluronan/curcumin aggregates. Treatment with
      chitosan/curcumin, gelatin/curcumin and hyaluronan/curcumin aggregates resulted
      in higher apoptosis rates of 45, 40 and 32 %, respectively, as compared to pure
      curcumin (less than 20 %) via Annexin V-FITC/PI analysis. Chitosan/curcumin
      aggregates induce the highest apoptosis effect (indicated by sub-G1 phase). In
      summary, chitosan/curcumin, gelatin/curcumin, and hyaluronan/curcumin aggregates
      represent higher anticancer proliferation properties in A549 cells than curcumin
      alone that exhibit great potential enhancement by either using fewer drugs or a
      decreased duration. 

PMID- 25595722
TI  - Not all approved antibiotic-loaded PMMA bone cement brands are the same: ranking
      using the utility materials selection concept.
AB  - In the literature on in vitro characterization of approved antibiotic-loaded
      poly(methyl methacrylate) bone cement brands, there is no information on the
      basis for selection of a given brand for use in cemented arthroplasties. This
      shortcoming is addressed in the present study. It involved determining four key
      properties (fatigue limit, fracture toughness, polymerization rate, and phosphate
      buffered saline diffusion coefficient) for six brands and then using the mean
      property values, in conjunction with a materials selection methodology, called
      the utility concept, to rank the brands. It is emphasized that the present work
      is an illustration of a rational approach to selection of a cement brand and, as
      such, the study findings are not intended to be recommendations regarding
      clinical use or otherwise of a brand. 

PMID- 25595723
TI  - Joining characteristics of titanium-based orthodontic wires connected by laser
      and electrical welding methods.
AB  - This study investigated the possibility of electrical and laser welding to
      connect titanium-based alloy (beta-titanium and nickel-titanium) wires and
      stainless-steel or cobalt-chromium alloy wires for fabrication of combination
      arch-wires. Four kinds of straight orthodontic rectangular wires (0.017 * 0.025
      inch) were used: stainless-steel (S-S), cobalt-chromium (Co-Cr), beta-titanium
      alloy (beta-Ti), and nickel-titanium (Ni-Ti). Homogeneous and heterogeneous end
      to-end joints (15 mm long each) were made by electrical welding and laser
      welding. Non-welded wires (30 mm long) were also used as a control. Maximum loads
      at fracture (N) and elongation (%) were measured by conducting tensile test. The
      data (n = 10) were statistically analyzed using analysis of variance/Tukey test
      (P < 0.05).The S-S/S-S and Co-Cr/Co-Cr specimens showed significantly higher
      values of the maximum load (ML) at fracture and elongation (EL) than those of the
      Ni-Ti/Ni-Ti and beta-Ti/beta-Ti specimens for electrical welding and those of the
      S-S/S-S and Co-Cr/Co-Cr specimens welded by laser. On the other hand, the laser
      welded Ni-Ti/Ni-Ti and beta-Ti/beta-Ti specimens exhibited higher values of the
      ML and EL compared to those of the corresponding specimens welded by electrical
      method. In the heterogeneously welded combinations, the electrically welded Ni
      Ti/S-S, beta-Ti/S-S and beta-Ti/Co-Cr specimens showed significantly (P < 0.05)
      higher ML and EL than those of the corresponding specimens welded by laser.
      Electrical welding exhibited the higher values of maximum load at fracture and
      elongation for heterogeneously welded combinations than laser-welding.

PMID- 25595724
TI  - Comparison of uncovered stent placement across versus above the main duodenal
      papilla for malignant biliary obstruction.
AB  - PURPOSE: To evaluate the differences in efficiency and complications of metal
      stent insertion across versus above the main duodenal papilla (MDP) in patients
      with malignant obstruction of the common bile duct (CBD). MATERIALS AND METHODS:
      Records of 98 consecutive patients who underwent stent insertion for malignant
      CBD obstruction between 2004 and 2010 were retrospectively reviewed. Fifty-one
      patients (group 1) and 47 patients (group 2) were treated with stent insertion
      across and above the MDP, respectively. Primary stent patency, overall survival,
      complications, and changes in serum bilirubin level following stent insertion
      were assessed. RESULTS: Infection appeared in 12 and four patients, respectively,
      in groups 1 and 2. The respective mean primary stent patency times were 307.8
      days +/- 20.2 and 490.7 days +/- 40.7, and mean survival times were 245.1 days +/
      17.4 and 286.3 days +/- 20.2. Bilirubin reduction rates were 55.7% +/- 16.6 and
      61.1% +/- 13.7 at 1 week and 84.2% +/- 5.7 and 86.2% +/- 5.7 at 1 month in groups
      1 and 2, respectively. In group 2, the rate of infection was significantly lower
      (P = .044) and primary stent patency was longer (P = .019). However, there was no
      significant difference between groups in survival time (P = .074) or bilirubin
      reduction rate at 1 week (P = .083) or 1 month (P = .082). CONCLUSIONS: Bile
      stent insertion above the MDP may achieve longer stent patency and a lower
      infection rate compared with placement across the MDP. For patients with
      malignant CBD obstruction, biliary stents should be placed above the papilla if
      papillary lesions are not invaded.

PMID- 25595725
TI  - Systematic review of the presentation of coagulation factor VIII inhibitors in
      rheumatic diseases: A potential cause of life-threatening hemorrhage.
AB  - OBJECTIVES: To provide a comprehensive review regarding the clinical presentation
      of acquired factor VIII (FVIII) inhibitors, also known as "acquired hemophilia,"
      in patients with rheumatic diseases. METHODS: A systematic MEDLINE search was
      conducted to identify English-language articles published from 1993 through
      January 10, 2012, providing details regarding the clinical presentation,
      laboratory evaluation, and management of a patient(s) with newly or previously
      diagnosed autoimmune disease coexistent with an acquired FVIII inhibitor.
      RESULTS: In total, 49 patients fulfilled the criteria for inclusion in the
      review; the greatest percentage (24.5%) had systemic lupus erythematosus,
      followed by rheumatoid arthritis (16%). The majority (78%) presented with
      spontaneous mucocutaneous or muscular bleeding. Prolonged activated partial
      thromboplastin time (aPTT) was identified in all of the 45 patients for whom
      results were provided. Five patients presented with an asymptomatic prolonged
      aPTT, which was attributed to a lupus anticoagulant in two patients, only one of
      whom actually had a coexisting lupus anticoagulant. Invasive procedures led to
      serious bleeding in both of these patients, one of whom died as a result. The
      majority (59%) of patients experienced complete or partial remission of their
      inhibitors, most (96%) after systemic eradicative therapy. A total of three (6%)
      patients died as a direct result of FVIII inhibitors. CONCLUSIONS: Although
      acquired FVIII inhibitors are rare in patients with autoimmune diseases, prompt
      diagnosis is essential to avoid extensive bleeding, which could be life
      threatening. Treatment requires eradication of the factor inhibitors.
      Rheumatologists must be able to distinguish acquired FVIII inhibitors from lupus
      anticoagulants.

PMID- 25595726
TI  - Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3
      methylglutaconic aciduria, a novel disorder of mitochondrial protein
      disaggregation.
AB  - Whole exome sequencing was used to investigate the genetic cause of mitochondrial
      disease in two siblings with a syndrome of congenital lamellar cataracts
      associated with nephrocalcinosis, medullary cysts and 3-methylglutaconic
      aciduria. Autosomal recessive inheritance in a gene encoding a mitochondrially
      targeted protein was assumed; the only variants which satisfied these criteria
      were c.1882C>T (p.Arg628Cys) and c.1915G>A (p.Glu639Lys) in the CLPB gene,
      encoding a heat shock protein/chaperonin responsible for disaggregating
      mitochondrial and cytosolic proteins. Functional studies, including quantitative
      PCR (qPCR) and Western blot, support pathogenicity of these mutations.
      Furthermore, molecular modelling suggests that the mutations disrupt interactions
      between subunits so that the CLPB hexamer cannot form or is unstable, thus
      impairing its role as a protein disaggregase. We conclude that accumulation of
      protein aggregates underlies the development of cataracts and nephrocalcinosis in
      CLPB deficiency, which is a novel genetic cause of 3-methylglutaconic aciduria. A
      common mitochondrial cause for 3-methylglutaconic aciduria appears to be
      disruption of the architecture of the mitochondrial membranes, as in Barth
      syndrome (tafazzin deficiency), Sengers syndrome (acylglycerol kinase deficiency)
      and MEGDEL syndrome (impaired remodelling of the mitochondrial membrane lipids
      because of SERAC1 mutations). We now propose that perturbation of the
      mitochondrial membranes by abnormal protein aggregates leads to 3
      methylglutaconic aciduria in CLPB deficiency. 

PMID- 25595727
TI  - Oleic acid increases mitochondrial reactive oxygen species production and
      decreases endothelial nitric oxide synthase activity in cultured endothelial
      cells.
AB  - Elevated plasma levels of free fatty acids (FFA) are associated with increased
      cardiovascular risk. This may be related to FFA-induced elevation of oxidative
      stress in endothelial cells. We hypothesized that, in addition to mitochondrial
      production of reactive oxygen species, endothelial nitric oxide synthase (eNOS)
      mediated reactive oxygen species production contributes to oleic acid (OA)
      induced oxidative stress in endothelial cells, due to eNOS uncoupling. We
      measured reactive oxygen species production and eNOS activity in cultured
      endothelial cells (bEnd.3) in the presence of OA bound to bovine serum albumin,
      using the CM-H2DCFDA assay and the L-arginine/citrulline conversion assay,
      respectively. OA induced a concentration-dependent increase in reactive oxygen
      species production, which was inhibited by the mitochondrial complex II inhibitor
      thenoyltrifluoroacetone (TTFA). OA had little effect on eNOS activity when
      stimulated by a calcium-ionophore, but decreased both basal and insulin-induced
      eNOS activity, which was restored by TTFA. Pretreatment of bEnd.3 cells with
      tetrahydrobiopterin (BH4) prevented OA-induced reactive oxygen species production
      and restored inhibition of eNOS activity by OA. Elevation of OA levels leads to
      both impairment in receptor-mediated stimulation of eNOS and to production of
      mitochondrial-derived reactive oxygen species and hence endothelial dysfunction.

PMID- 25595728
TI  - The inhibitory effect of granisetron on ventrolateral medulla neuron responses to
      colorectal distension in rats.
AB  - Irritable bowel syndrome (IBS) is one of the most widespread functional
      gastrointestinal disorders characterized by abdominal pain. A key
      pathophysiological mechanism of abdominal pain is associated with disturbances of
      serotonergic transmission in feedback control loops of endogenous pain modulation
      in which the ventrolateral medulla (VLM) plays an important role. The receptors
      to serotonin (5-HT), and particularly the serotonin 3 (5-HT3) receptors have been
      extensively used as a potential target for abdominal pain treatment of IBS
      patients due to antinociceptive features of the 5-HT3 receptor antagonists. The
      precise mechanisms underlying the antinociceptive action of these antagonists
      remain unclear. The main objective of our study was to evaluate the involvement
      of the 5-HT3 receptors in abdominal pain transmission within the VLM. Experiments
      were carried out on urethane-anaesthetized rats using the animal model of
      abdominal pain. Noxious colorectal distension (CRD) with a pressure of 80mmHg
      induced a significant increase in VLM neuron-evoked activity and depressor
      reactions (171.1+/-12.7% and 64+/-1.8% to baseline, accordingly). Selective
      blockade of the 5-HT3 receptors with granisetron at doses of 1.0 or 2.0mg/kg
      (i.v) resulted in long-lasting (90min) dose-dependent inhibition of VLM neuron
      evoked activity and depressor reactions. When brainstem dorsal surface
      applications of granisetron (10 or 20uM) were used, the changes were more
      pronounced. These results suggest involvement of the 5-HT3 receptors in abdominal
      pain transmission within the VLM, which will be discussed in relation to the
      central antinociceptive effect of granisetron. 

PMID- 25595730
TI  - Impact of Otolaryngology in the diagnosis of early oesophageal malignancy.
AB  - INTRODUCTION: A large number of patients present in Otolaryngology clinics with
      vague upper gastro intestinal symptoms, some potentially originating from the
      oesophagus. In the United Kingdom there is no consensus for investigation
      protocols. The concern is that diagnosis of early oesophageal malignancy can be
      delayed with detrimental effects to the prognosis of the patient. The aim of this
      paper is to attempt to establish the impact of Ear Nose and Throat (ENT) work up
      in the diagnostic pathway of these patients. METHODS: Retrospective analysis of
      case notes of newly diagnosed oesophageal carcinoma over a 15 month period.
      RESULTS: Sixty five patients with a new diagnosis of oesophageal carcinoma were
      identified from the upper GI cancer network. A cohort of 7 patients was initially
      referred to ENT with related symptoms. Delays occurred at different stages during
      the course of their diagnostic pathways. Only 2 patients were diagnosed from ENT
      prior to referral to upper GI. CONCLUSION: We support the creation of one stop
      clinics incorporating the use of transnasal oesophagoscopy. The current
      literature is discussed.

PMID- 25595729
TI  - The effects of fluoxetine on circulating oxidative damage parameters in rats
      exposed to aortic ischemia-reperfusion.
AB  - Oxidative stress and reperfusion injury may develop in different ischemia
      reperfusion (IR) models. Growing evidence links altered lipid protein redox
      homeostasis with IR. The effect of fluoxetine (FLX; N-methyl-3-[4
      (trifluoromethyl) phenoxy] benzenepropanamine), on the lipid protein redox
      homeostasis mechanisms in the rats exposed to aortic IR is unclear. We aimed to
      investigate the effects of FLX on circulating protein oxidation and lipid
      peroxidation parameters, such as ischemia modified albumin (IMA), lipid
      hydroperoxide (LOOH), prooxidant antioxidant balance (PAB), erythrocyte
      glutathione (GSH), CuZn-superoxide dismutase (CuZn-SOD), ferric reducing
      antioxidant power (FRAP), as potential IR biomarkers. Wistar rats were randomized
      into three groups (n=7/group): 1) Control (sham laparotomy); 2) IR without FLX,
      (60min ischemia and 120min reperfusion); 3) IR with FLX (FLX+IR) (FLX
      20mg/kg/day, i.p. for three days before surgery). All of the aforementioned
      parameters (IMA, LOOH, PAB, GSH, CuZn-SOD, and FRAP) were measured
      spectrophotometrically. IMA, LOOH, and PAB levels in IR group were significantly
      higher than the control (P<0.01 respectively) and fluoxetine groups (P<0.01,
      P<0.01, and P<0.05 respectively), whereas CuZn-SOD activities, GSH and FRAP were
      significantly lower in IR groups. Fluoxetine group significantly reduced IMA when
      compared to IR group (P<0.001) and control group (P<0.01). With respect to IMA,
      LOOH and PAB, impaired redox homeostasis is substantially more prominent in
      aortic IR. The antidepressant FLX has profitable effects on circulating redox
      status in rats exposed to aortic IR. FLX administration before IR might decrease
      the surgery-enhanced free radical production; taken together, the antioxidant
      effects of FLX supplementation should be considered in future studies. 

PMID- 25595731
TI  - Role of two Nomuraea rileyi transmembrane sensors Sho1p and Sln1p in adaptation
      to stress due to changing culture conditions during microsclerotia development.
AB  - Microsclerotia (MS) formation was successfully induced in Nomuraea rileyi in
      liquid amended medium (AM) culture. To investigate how N. rileyi senses growth
      stress and regulates MS differentiation, based on transcriptome library, sho1 and
      sln1 genes were cloned. The transcription levels of sho1 and sln1 were
      upregulated in response to the changing culture conditions. To determine the
      functions of sho1 and sln1, gene-silencing mutants (sholi, sln1i and shol&sln1i)
      were generated using RNA silencing technology. The significant phenotypic changes
      in the mutants included reduced conidial yields by 22.72, 40.27, and 63.67 % and
      virulence by 24.53, 25.74, and 59.04 %, respectively. Furthermore, the mutants
      presented decreased MS yields by approximately 96 % under changing culture
      conditions. Our results confirmed the crucial role of Sho1p and Sln1p in sensing
      growth stress due to changing culture conditions and regulating MS
      differentiation.

PMID- 25595732
TI  - Fluorescence-guided bladder tumour resection: impact on survival after radical
      cystectomy.
AB  - PURPOSE: To investigate whether photodynamic diagnosis (PDD)-guided bladder
      tumour resection (TUR-BT) is of prognostic value in patients undergoing
      subsequent radical cystectomy (RC) for bladder cancer (BC). METHODS: In 224
      consecutive patients who underwent RC and bilateral pelvic lymphadenectomy for BC
      between 2002 and 2010 (median follow-up 29 months [IQR 8-59]), we retrospectively
      investigated whether patients had previously undergone PDD-guided
      (hexaminolevulinate [HAL] vs. 5-aminolevulinate [ALA]) versus white light (WL)
      TUR-BT. Kaplan-Meier analysis was used to estimate recurrence-free survival
      (RFS), cancer-specific survival (CSS) and overall survival (OS) using log-rank
      and Cox regression model for uni- and multivariable analysis. RESULTS: Of the 224
      patients, 66 (29.5 %) underwent HAL-, 23 (10.3 %) ALA- and 135 (60.2 %) WL-TUR-BT
      before RC. The 3-year RFS/CSS/OS was 77.8/83.9/74.0 % for HAL-, 53.6/74.5/60.9 %
      for ALA- and 52.4/59.7/56.5 % for WL-TUR-BT (p = 0.002/0.023/0.037 for HAL vs.
      WL/ALA). PDD-TUR-BT was associated with a higher number of TUR-BTs before RC (p <
      0.001) and re-resections (p = 0.015), a longer time between the first TUR-BT and
      RC (p = 0.044) and a lower rate of post-operative systemic chemotherapy (p =
      0.001). In multivariable analysis, performance of HAL-TUR-BT, pathologic tumour
      and nodal stage as well as soft tissue surgical margin status were independent
      predictors for RFS, CSS and OS. CONCLUSIONS: This series indicates for the first
      time that HAL-guided TUR-BT is an independent predictor for improved survival
      after RC.

PMID- 25595733
TI  - [Consensus of the Brazilian Society of Rheumatology for the diagnosis, management
      and treatment of lupus nephritis].
AB  - OBJECTIVE: To develop recommendations for the diagnosis, management and treatment
      of lupus nephritis in Brazil. METHOD: Extensive literature review with a
      selection of papers based on the strength of scientific evidence and opinion of
      the Commission on Systemic Lupus Erythematosus members, Brazilian Society of
      Rheumatology. RESULTS AND CONCLUSIONS: 1) Renal biopsy should be performed
      whenever possible and if this procedure is indicated; and, when the procedure is
      not possible, the treatment should be guided with the inference of histologic
      class. 2) Ideally, measures and precautions should be implemented before starting
      treatment, with emphasis on attention to the risk of infection. 3) Risks and
      benefits of treatment should be shared with the patient and his/her family. 4)
      The use of hydroxychloroquine (preferably) or chloroquine diphosphate is
      recommended for all patients (unless contraindicated) during induction and
      maintenance phases. 5) The evaluation of the effectiveness of treatment should be
      made with objective criteria of response (complete remission/partial
      remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as
      antiproteinuric agents for all patients (unless contraindicated). 7) The
      identification of clinical and/or laboratory signs suggestive of proliferative or
      membranous glomerulonephritis should indicate an immediate implementation of
      specific therapy, including steroids and an immunosuppressive agent, even though
      histological confirmation is not possible. 8) Immunosuppressives must be used
      during at least 36 months, but these medications can be kept for longer periods.
      Its discontinuation should only be done when the patient achieve and maintain a
      sustained and complete remission. 9) Lupus nephritis should be considered as
      refractory when a full or partial remission is not achieved after 12 months of an
      appropriate treatment, when a new renal biopsy should be considered to assist in
      identifying the cause of refractoriness and in the therapeutic decision.

PMID- 25595734
TI  - Combinations of long peptide sequence blocks can be used to describe toxin
      diversification in venomous animals.
AB  - An important mechanism for the evolution of toxins in venomous animals is
      believed to be the acquisition of genes encoding proteins that switch from
      physiological to toxic roles following gene duplication. The 'reverse
      recruitment' hypothesis pertains that these genes can also revert back to
      physiological functions, although such events are thought to be rare. A non
      supervised homology searching method was developed which allowed the peptide
      diversity of animal toxins to be described as combinations between limited
      numbers of amino-acid sequence blocks we called 'tox-bits'. Taking the
      phospholipase A2 (PLA2) protein family as an example, a Bernoulli Trial was used
      to test if 'tox-bits' were robust enough to distinguish between peptides with
      physiological or toxin functions. The analysis revealed that discrimination was
      indeed possible, and supports the very recent 'restriction' hypothesis whereby
      genes with the potential to encode toxic functions have likely been independently
      recruited into venom systems and therefore require few, if any, reverse
      recruitment events. The development of 'tox-bits' provides a novel bioinformatics
      tool to allow recognition of toxins from other proteins in genome sequences,
      facilitating the study of gene recruitment and duplication strategies in venom
      diversification. The 'tox-bits' library is freely available at
      http://bioserv.pbf.hr/blocks.zip. 

PMID- 25595737
TI  - Deletion of Stat3 in hematopoietic cells enhances thrombocytosis and shortens
      survival in a JAK2-V617F mouse model of MPN.
AB  - The acquired somatic JAK2-V617F mutation is present in >80% of patients with
      myeloproliferative neoplasms (MPNs). Stat3 plays a role in hematopoietic
      homeostasis and might influence the JAK2-V617F-driven MPN phenotype. We crossed
      our transgenic SclCre;V617F mice with a conditional Stat3 knockout strain and
      performed bone marrow transplantations into lethally irradiated recipient mice.
      The deletion of Stat3 increased the platelet numbers in SclCre;V617F;Stat3(fl/fl)
      mice compared with SclCre;V617F;Stat3(fl/+) or SclCre;V617F;Stat3(+/+) mice.
      Stat3 deletion also normalized JAK2-V617F-induced neutrophilia. Megakaryocyte
      progenitors were elevated, especially in the spleen, and a slight increase in
      myelofibrosis was noted. We observed increased mRNA expression levels of Stat1
      and Stat1 target genes and augmented phosphorylation of Stat1 protein in bone
      marrow and spleen of JAK2-V617F mice after Stat3 deletion. The survival of Stat3
      deficient mice expressing JAK2-V617F was reduced. Inflammatory bowel disease,
      previously associated with shortened survival of Stat3-deficient mice, was less
      prominent in the bone marrow transplantation setting, possibly by limiting
      deletion of Stat3 to hematopoietic tissues only. In conclusion, deletion of Stat3
      in hematopoietic cells from JAK2-V617F mice did not ameliorate the course of MPN,
      but rather enhanced thrombocytosis and shortened the overall survival. 

PMID- 25595738
TI  - DNA methylation modulates HERV-E expression in CD4+ T cells from systemic lupus
      erythematosus patients.
AB  - BACKGROUND: Previous studies have reported that the DNA of T cells from systemic
      lupus erythematosus (SLE) patients contains global hypomethylation that may
      contribute to the development of SLE. Human endogenous retroviruses (HERVs) are
      encoded within the genomes of all higher eukaryotes and are of special interest
      where autoimmune disorders are concerned. Until recently, minimal effort has been
      made to identify specific HERVs associated with SLE and to explore their precise
      mechanism of expression. OBJECTIVE: To examine the expression of HERVs associated
      with SLE and elucidate the effect of ultraviolet B (UVB) exposure on SLE
      associated HERV expression in CD4+ T cells from patients with SLE. METHODS:
      Fifteen patients with SLE and 10 healthy controls were enrolled in the study. The
      mRNA expression of selected HERVs and the methylation status of the long terminal
      repeats (LTRs) in SLE-related HERVs in CD4+ T cells were investigated.
      Furthermore, CD4+ T cells treated with 5-aza-deoxycytidine (5-aza C) and UVB were
      analyzed. Reverse-transcription PCR (RT-PCR), quantitative real-time PCR (qRT
      PCR) and bisulfite sequencing analysis were employed. RESULTS: HERV-E mRNA
      expression was higher in lupus CD4+ T cells than in cells from healthy controls,
      whereas the mRNA expression levels of HERV-K, HERV-K10 and HERV-W were comparable
      in SLE patients and healthy controls. Additionally, the HERV-E mRNA expression
      level was positively correlated with SLE disease activity. Furthermore, the HERV
      E LTR methylation level was decreased and was negatively correlated to the HERV-E
      mRNA expression level in lupus CD4+ T cells. Finally, lupus CD4+ T cells showed
      markedly decreased HERV-E LTR2C methylation levels and increased HERV-E mRNA
      expression after treatment with 5-aza C or UVB. CONCLUSION: HERV-E is involved in
      the development of SLE. HERV-E transcription may be activated via inhibition of
      LTR methylation in lupus CD4+ T cells.

PMID- 25595736
TI  - Critical role of CD4 T cells in PF4/heparin antibody production in mice.
AB  - Antibodies specific for platelet factor 4 (PF4)/heparin complexes are central to
      the pathogenesis of heparin-induced thrombocytopenia. Marginal zone B cells
      appear to be the source of such antibodies, but whether T-cell help is required
      is unclear. Here, we showed that induction of PF4/heparin-specific antibodies by
      PF4/heparin complexes was markedly impaired in mice depleted of CD4 T cells by
      anti-CD4 antibodies. Furthermore, Rag1-deficient recipient mice produced
      PF4/heparin-specific antibodies upon PF4/heparin challenge when reconstituted
      with a mixture of wild-type splenic B cells and splenocytes from B-cell-deficient
      (MUMT) mice but not splenocytes from T- and B-cell-deficient (Rag1 knockout)
      mice. Lastly, mice with B cells lacking CD40, a B-cell costimulatory molecule
      that helps T-cell-dependent B-cell responses, displayed a marked reduction of
      PF4/heparin-specific antibody production following PF4/heparin challenge.
      Together, these findings show that helper T cells play a critical role in
      production of PF4/heparin-specific antibodies. 

PMID- 25595739
TI  - The role of lipin-1 in the pathogenesis of alcoholic fatty liver.
AB  - AIMS: The aim of this review was to focus on the knowledge of the role of lipin-1
      in the pathogenesis of alcoholic fatty liver. METHODS: Systematic review of
      animal clinical and cell level studies related to the function of lipin-1 on
      alcoholic fatty liver, alcoholic hepatitis and alcoholic liver cirrhosis disease.
      RESULT: Ethanol could increase the expression of lipin-1 through the AMPK-SREBP-1
      signaling and dramatically increase the ratio of Lpin1beta to Lpin1alpha by SIRT1
      SFRS10-Lpin1beta/alpha axis in the liver. Moreover, research has shown that over
      expression of lipin-1 could also remarkably suppress very low density lipoprotein
      triacylglyceride secretion. Last, lipin-1 has potent anti-inflammatory property.
      CONCLUSION: In conclusion, lipin-1 has dual functions in lipid metabolism. In the
      cytoplasm, lipin-1beta functions as a Mg(2+)-dependent phosphatidic acid
      phosphohydrolase (PAP) enzyme in triglyceride synthesis pathways. In the nucleus,
      lipin-1alpha acts as a transcriptional co-regulator to regulate the capacity of
      the liver for fatty acid oxidation and activity of the lipogenic enzyme. In
      hepatocytes of alcoholic fatty liver disease (AFLD), ethanol increases the
      expression of lipin-1 through the AMPK-SREBP-1 signaling and the Lpin1beta/alpha
      ratio by SIRT1-SFRS10- Lpin1beta/alpha axis. Of course, in addition to that,
      ethanol could also produce the PAP activity and interrupt the nucleus function of
      lipin-1. Furthermore, over-expression of lipin-1 could remarkably suppress very
      low-density lipoprotein-triacylglyceride (VLDL-TAG) secretion. In the end,
      endogenous lipin-1 has potent anti-inflammatory property. Increased synthesis of
      TAG, decreased fatty acid oxidation, impaired VLDL-TAG secretion and activated
      inflammatory factors act together to exacerbate the development of AFLD.

PMID- 25595735
TI  - Obligatory role of neuronal nitric oxide synthase in the heart's antioxidant
      adaptation with exercise.
AB  - Excessive oxidative stress in the heart results in contractile dysfunction. While
      antioxidant therapies have been a disappointment clinically, exercise has shown
      beneficial results, in part by reducing oxidative stress. We have previously
      shown that neuronal nitric oxide synthase (nNOS) is essential for
      cardioprotective adaptations caused by exercise. We hypothesize that part of the
      cardioprotective role of nNOS is via the augmentation of the antioxidant defense
      with exercise by positively shifting the nitroso-redox balance. Our results show
      that nNOS is indispensable for the augmented anti-oxidant defense with exercise.
      Furthermore, exercise training of nNOS knockout mice resulted in a negative shift
      in the nitroso-redox balance resulting in contractile dysfunction. Remarkably,
      overexpressing nNOS (conditional cardiac-specific nNOS overexpression) was able
      to mimic exercise by increasing VO2max. This study demonstrates that exercise
      results in a positive shift in the nitroso-redox balance that is nNOS-dependent.
      Thus, targeting nNOS signaling may mimic the beneficial effects of exercise by
      combating oxidative stress and may be a viable treatment strategy for heart
      disease. 

PMID- 25595740
TI  - Formulation considerations in the design of topical, polymeric film-forming
      systems for sustained drug delivery to the skin.
AB  - Polymeric film-forming systems (FFSs) are potential drug delivery systems for
      topical application to the skin. The FFSs form thin and transparent polymeric
      films in situ upon solvent evaporation. Their application convenience and
      cosmetic attributes, superior to conventional semi-solids, may offer improved
      patient compliance. This study represents the first phase of an investigation
      into the use of FFSs for prolonged dermal drug delivery. FFS formulations were
      distinguished based on their ability to sustain the release of betamethasone 17
      valerate (BMV) in vitro over 72 h. The effect of film-forming polymer
      (hydrophilic: hydroxypropyl cellulose (KlucelTM LF); hydrophobic:
      polymethacrylate copolymers (Eudragit(r) NE and Eudragit(r) RS), and polyacrylate
      copolymer (Dermacryl(r) 79) was first determined, and then the impact of
      incorporation of plasticisers (triethyl citrate, tributyl citrate, and dibutyl
      sebacate) was examined. The Klucel film released a significantly higher amount of
      BMV than the hydrophobic FFS, 42 versus 4 MUg/cm(2), respectively. The release
      was increased when a plasticiser was incorporated, and with higher enhancement
      ratios achieved with the more lipophilic plasticisers. In conclusion, the results
      show that FFSs can sustain drug release (hence representing useful systems for
      prolonged dermal therapy) and emphasise the importance of the formulation on drug
      delivery, with the type of polymer being of greatest significance.

PMID- 25595741
TI  - Surgical treatment of medically refractory gastroparesis in the morbidly obese.
AB  - INTRODUCTION: Surgical management of medically refractory gastroparesis remains a
      challenge. Case series and small retrospective studies describe clinical benefits
      from surgical intervention; however, no study reports the efficacy of gastric
      electrical stimulation (GES) or Roux-en-Y gastrojejunostomy with or without near
      total gastrectomy (RYGJ) in morbidly obese patients with severe gastroparesis.
      METHODS: A chart review was performed on all morbidly obese patients (BMI > 35
      kg/m(2)) who underwent GES or RYGJ for medically refractory gastroparesis from
      March 2002 to December 2012 at the Cleveland Clinic. The main outcomes examined
      were symptom improvement, postoperative complications, and change in BMI.
      RESULTS: A total of 20 morbidly obese patients underwent GES placement. Seven
      morbidly obese patients had RYGJ with or without resection of the remnant stomach
      surgery. All operations were completed laparoscopically. In GES group, 18
      patients had initial symptom improvement (90%) and 11 (55%) rated their symptom
      improved at the last follow-up. During the average 23 months' follow-up, 9
      patients (45%) experienced at least one readmission for gastrointestinal reasons.
      Early complications included two infections at a simultaneously placed J-tube
      site and one seroma. In the RYGJ group, all patients, including 4 patients who
      failed GES and subsequently converted to RYGJ, experienced short-term symptom
      improvement and 5 patients (71%) rated their symptoms as improved at last follow
      up. One duodenal stump leak happened in the RYGJ group. There were no 30-day
      mortalities in either group. The BMI change after GES implantation was 0.6 +/- 4
      kg/m(2) versus -7.7 +/- 4 kg/m(2) after RYGJ (p < 0.01). CONCLUSION: GES
      implantation and RYGJ are both effective in terms of symptom control for
      medically refractory gastroparesis in morbidly obese. Both options can be
      performed in a minimally invasive fashion with low morbidity. Patients who have
      no improvement of symptoms for refractory gastroparesis after GES implantation
      can be successfully converted laparoscopically to RYGJ.

PMID- 25595743
TI  - Declining relative risk for myocardial infarction among HIV-positive compared
      with HIV-negative individuals with access to care.
AB  - Concerns remain for an increased myocardial infarction (MI) risk among
      individuals infected with human immunodeficiency virus (HIV). We conducted a
      cohort study evaluating MI risk from 1996 to 2011 by HIV status. The adjusted MI
      rate ratio for HIV status declined over time, reaching 1.0 (95% confidence
      interval, .7-1.4) in 2010-2011, the most recent study period. 

PMID- 25595742
TI  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: old
      foe, emerging threat.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae present an
      ever-growing burden in the hospital and community settings, across all ages and
      demographics. Infections due to ESBL-containing pathogens continue to be
      associated with significant morbidity and mortality worldwide. With widespread
      empiric broad-spectrum beta-lactam use creating selective pressure, and the
      resultant emergence of stable, rapidly proliferating ESBL-producing clones with
      continued horizontal gene transfer across genera, addressing this issue remains
      imperative. Although well characterized in adults, the epidemiology, risk
      factors, outcomes, therapies, and control measures for ESBL-producing bacteria
      are less appreciated in children. This analysis provides a brief summary of ESBL
      producing Enterobacteriaceae in children, with a focus on recent clinical and
      molecular data regarding colonization and infection in nonoutbreak settings. 

PMID- 25595744
TI  - Myocardial infarction among Danish HIV-infected individuals: population
      attributable fractions associated with smoking.
AB  - BACKGROUND: Human immunodeficiency virus-infected individuals have increased risk
      of myocardial infarction (MI); however, the contribution from smoking and
      potentiating effects of HIV are controversial. METHODS: From the Danish HIV
      Cohort Study and the Copenhagen General Population Study, we identified 3251 HIV
      infected individuals and 13 004 population controls matched on age and gender.
      Data on MI were obtained from the National Hospital Registry and the National
      Registry of Causes of Death. We calculated adjusted incidence rate ratios (aIRR)
      for risk of MI and population-attributable fractions (PAF) of MI associated with
      smoking. RESULTS: In never smokers, HIV was not associated with an increased risk
      of MI (aIRR, 1.01; 95% confidence interval [CI], .41-2.54). In previous and
      current smokers, HIV was associated with a substantially increased risk of MI
      (aIRR, 1.78; 95% CI, .75-4.24 and aIRR, 2.83; 95% CI, 1.71-4.70). The PAF
      associated with ever smoking (previous or current) was 72% (95% CI, 55%-82%) for
      HIV-infected individuals and 24% (95% CI, 3%-40%) for population controls. If all
      current smokers stopped smoking, 42% (95% CI, 21%-57%) and 21% (95% CI, 12%-28%)
      of all MIs could potentially be avoided in these 2 populations. CONCLUSIONS:
      Smoking is associated with a higher risk of MI in the HIV-infected population
      than in the general population. Approximately 3 of 4 MIs among HIV-infected
      individuals are associated with ever smoking compared with only 1 of 4 MIs among
      population controls. Smoking cessation could potentially prevent more than 40% of
      MIs among HIV-infected individuals, and smoking cessation should be a primary
      focus in modern HIV care.

PMID- 25595745
TI  - Hepatitis C virus antibody positivity and predictors among previously undiagnosed
      adult primary care outpatients: cross-sectional analysis of a multisite
      retrospective cohort study.
AB  - BACKGROUND: Hepatitis C virus (HCV) testing guidance issued by the Centers for
      Disease Control and Prevention in 1998 recommends HCV antibody (anti-HCV) testing
      for persons with specified risk factors. The purpose of this study was to
      determine the prevalence and predictors of anti-HCV positivity among primary care
      outpatients and estimate the proportion of unidentified anti-HCV-positive (anti
      HCV+) persons using risk-based testing. METHODS: We analyzed electronic medical
      record data from a 4-site retrospective study. Patients were aged >=18 years,
      utilized >=1 outpatient primary care service(s) between 2005 and 2010, and had no
      documented evidence of prior HCV diagnosis. Among persons tested for anti-HCV, we
      fit a multilevel logistic regression model to identify patient-level independent
      predictors of anti-HCV positivity. We estimated the proportion of unidentified
      anti-HCV+ persons by using multiple imputation to assign anti-HCV results to
      untested patients. RESULTS: We observed 209 076 patients for a median of 5 months
      (interquartile range, 1-23 months). Among 17 464 (8.4%) patients who were tested
      for anti-HCV, 6.4% (n=1115) were positive. We identified history of injection
      drug use (adjusted odds ratio [95% confidence interval], 6.3 [5.2-7.6]), 1945
      1965 birth cohort (4.4 [3.8-5.1]), and elevated alanine aminotransferase levels
      (4.8 [4.2-5.6]) as independently associated with anti-HCV positivity. We
      estimated that 81.5% (n=4890/6005) of anti-HCV+ patients were unidentified using
      risk-based testing. CONCLUSIONS: In these outpatient primary care settings, risk
      based testing may have missed 4 of 5 newly enrolled patients who are anti-HCV+.
      Without knowing their status, unidentified anti-HCV+ persons cannot receive
      further clinical evaluation or antiviral treatment, and are unlikely to benefit
      from secondary prevention recommendations to limit disease progression and
      mortality.

PMID- 25595746
TI  - The first association of a primary amebic meningoencephalitis death with
      culturable Naegleria fowleri in tap water from a US treated public drinking water
      system.
AB  - BACKGROUND: Naegleria fowleri is a climate-sensitive, thermophilic ameba found in
      warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM),
      which is almost universally fatal, occurs when N. fowleri-containing water enters
      the nose, typically during swimming, and migrates to the brain via the olfactory
      nerve. In August 2013, a 4-year-old boy died of meningoencephalitis of unknown
      etiology in a Louisiana hospital. METHODS: Clinical and environmental testing and
      a case investigation were initiated to determine the cause of death and to
      identify potential exposures. RESULTS: Based on testing of cerebrospinal fluid
      and brain specimens, the child was diagnosed with PAM. His only reported water
      exposure was tap water; in particular, tap water that was used to supply water to
      a lawn water slide on which the child had played extensively prior to becoming
      ill. Water samples were collected from both the home and the water distribution
      system that supplied the home and tested; N. fowleri was identified in water
      samples from both the home and the water distribution system. CONCLUSIONS: This
      case is the first reported PAM death associated with culturable N. fowleri in tap
      water from a US treated drinking water system. This case occurred in the context
      of an expanding geographic range for PAM beyond southern states, with recent case
      reports from Minnesota, Kansas, and Indiana. This case also highlights the role
      of adequate disinfection throughout drinking water distribution systems and the
      importance of maintaining vigilance when operating drinking water systems using
      source waters with elevated temperatures.

PMID- 25595747
TI  - The spectrum of engagement in HIV care: how is it in Shandong Province, China?

PMID- 25595749
TI  - Seasonality of both bacteremic and nonbacteremic pneumonia coincides with viral
      lower respiratory tract infections in early childhood, in contrast to
      nonpneumonia invasive pneumococcal disease, in the pre-pneumococcal conjugate
      vaccine era.
AB  - We assessed the seasonality of viral lower respiratory tract infections (V-LRI),
      bacteremic pneumonia, nonbacteremic pneumonia and nonpneumonia invasive
      pneumococcal diseases (IPD) in the pre-PCV era. Both bacteremic and nonbacteremic
      pneumonia seasonality peaked in winter, coinciding with V-LRI seasonality,
      whereas non-pneumonia IPD peaked in autumn before V-LRI increase, suggesting
      different pathogenesis. 

PMID- 25595748
TI  - Point-of-prescription interventions to improve antimicrobial stewardship.
AB  - Antimicrobial stewardship is pivotal to improving patient outcomes, reducing
      adverse events, decreasing healthcare costs, and preventing further emergence of
      antimicrobial resistance. In an era in which antimicrobial resistance is
      increasing, judicious antimicrobial use is the responsibility of every healthcare
      provider. Antimicrobial stewardship programs (ASPs) have made headway in
      improving antimicrobial prescribing using such "top-down" methods as formulary
      restriction and prospective audit with feedback; however, engagement of
      prescribers has not been fully explored. Strategies that include frontline
      prescribers and other unit-based healthcare providers have the potential to
      expand stewardship, both to augment existing centralized ASPs and to provide
      alternative approaches to perform stewardship at healthcare facilities with
      limited resources. This review discusses interventions focusing on antimicrobial
      prescribing at the point of prescription as well as a pilot project to engage
      unit-based healthcare providers in antimicrobial stewardship. 

PMID- 25595751
TI  - Editorial commentary: improving prescribers to advance antimicrobial stewardship.

PMID- 25595750
TI  - Editorial commentary: Myocardial infarction in HIV-infected persons: time to
      focus on the silent elephant in the room?

PMID- 25595752
TI  - Occurrence of stomatal patchiness and its spatial scale in leaves from various
      sizes of trees distributed in a South-east Asian tropical rainforest in
      Peninsular Malaysia.
AB  - In this study, we demonstrated the occurrence of stomatal patchiness and its
      spatial scale in leaves from various sizes of trees grown in a lowland
      dipterocarp forest in Peninsular Malaysia. To evaluate the patterns of stomatal
      behavior, we used three techniques simultaneously to analyze heterobaric or
      homobaric leaves from five tree species ranging from 0.6 to 31 m in height: (i)
      diurnal changes in chlorophyll fluorescence imaging, (ii) observation and
      simulation of leaf gas-exchange rates and (iii) a pressure-infiltration method.
      Measurements were performed in situ with 1000 or 500 MUmol m(-2) s(-1)
      photosynthetic photon flux density. Diurnal patterns in the spatial distribution
      of photosynthetic electron transport rate (J) mapped from chlorophyll
      fluorescence images, a comparison of observed and simulated leaf gas-exchange
      rates, and the spatial distribution of stomatal apertures obtained from the acid
      fuchsin-infiltrated area showed that patchy stomatal closure coupled with severe
      midday depression of photosynthesis occurred in Neobalanocarpus heimii (King)
      Ashton, a higher canopy tree with heterobaric leaves due to the higher leaf
      temperature and vapor pressure deficit. However, subcanopy or understory trees
      showed uniform stomatal behavior throughout the day, although they also have
      heterobaric leaves. These results suggest that the occurrence of stomatal
      patchiness is determined by tree size and/or environmental conditions. The
      analysis of spatial scale by chlorophyll fluorescence imaging showed that several
      adjacent anatomical patches (lamina areas bounded by bundle-sheath extensions
      within the lamina) may co-operate for the distributed patterns of J and stomatal
      apertures.

PMID- 25595753
TI  - Differentiation of persistent anatomical defensive structures is costly and
      determined by nutrient availability and genetic growth-defence constraints.
AB  - Conifers exhibit a number of chemical and anatomical mechanisms to defend against
      pests and pathogens. Theory predicts an increased investment in plant defences
      under limited nutrient availability, but while this has been demonstrated for
      chemical defences, it has rarely been shown for anatomical defensive structures.
      In a long-lived woody plant, we tested the hypothesis that limited nutrient
      availability may promote an improved differentiation of persistent anatomical
      defences. We also hypothesized that the costs of differentiation of those long
      term anatomical structures may be determined by genetic constraints on early
      growth potential. Using Pinus pinaster Ait. juveniles, we performed a greenhouse
      study with 15 half-sib families subjected to experimental manipulation of
      phosphorus (P) availability and herbivory-related induced responses. When plants
      were ~30 cm high, half of the plant material was treated with methyl jasmonate to
      induce defences, and 2 weeks later plants were harvested and the abundance of
      resin canals in the cortex and xylem was assessed. Density of constitutive resin
      canals in the cortex and the total canal system was ~1.5-fold higher in plants
      under limited P availability than in fully fertilized plants. Availability of P
      did not significantly influence the inducibility of resin canal traits. We found
      negative genetic correlations between plant growth and the density of
      constitutive canals in the xylem and total canal system, but only under
      conditions of limited nutrition. These results demonstrate for the first time
      that differentiation of constitutive anatomical-based defences is affected by P
      limitation. Moreover, results also evidence the existence of genetic constraints
      between plant growth and constitutive defensive investment, where lineages with
      the highest growth potential showed the lowest investment in constitutive resin
      canals. 

PMID- 25595754
TI  - A portable NMR sensor to measure dynamic changes in the amount of water in living
      stems or fruit and its potential to measure sap flow.
AB  - Nuclear magnetic resonance (NMR) and NMR imaging (magnetic resonance imaging)
      offer the possibility to quantitatively and non-invasively measure the presence
      and movement of water. Unfortunately, traditional NMR hardware is expensive,
      poorly suited for plants, and because of its bulk and complexity, not suitable
      for use in the field. But does it need to be? We here explore how novel, small
      scale portable NMR devices can be used as a flow sensor to directly measure xylem
      sap flow in a poplar tree (Populus nigra L.), or in a dendrometer-like fashion to
      measure dynamic changes in the absolute water content of fruit or stems. For the
      latter purpose we monitored the diurnal pattern of growth, expansion and
      shrinkage in a model fruit (bean pod, Phaseolus vulgaris L.) and in the stem of
      an oak tree (Quercus robur L.). We compared changes in absolute stem water
      content, as measured by the NMR sensor, against stem diameter variations as
      measured by a set of conventional point dendrometers, to test how well the
      sensitivities of the two methods compare and to investigate how well diurnal
      changes in trunk absolute water content correlate with the concomitant diurnal
      variations in stem diameter. Our results confirm the existence of a strong
      correlation between the two parameters, but also suggest that dynamic changes in
      oak stem water content could be larger than is apparent on the basis of the stem
      diameter variation alone. 

PMID- 25595755
TI  - Improved production of propionic acid in Propionibacterium jensenii via
      combinational overexpression of glycerol dehydrogenase and malate dehydrogenase
      from Klebsiella pneumoniae.
AB  - Microbial production of propionic acid (PA), an important chemical building block
      used as a preservative and chemical intermediate, has gained increasing attention
      for its environmental friendliness over traditional petrochemical processes. In
      previous studies, we constructed a shuttle vector as a useful tool for
      engineering Propionibacterium jensenii, a potential candidate for efficient PA
      synthesis. In this study, we identified the key metabolites for PA synthesis in
      P. jensenii by examining the influence of metabolic intermediate addition on PA
      synthesis with glycerol as a carbon source under anaerobic conditions. We also
      further improved PA production via the overexpression of the identified
      corresponding enzymes, namely, glycerol dehydrogenase (GDH), malate dehydrogenase
      (MDH), and fumarate hydratase (FUM). Compared to those in wild-type P. jensenii,
      the activities of these enzymes in the engineered strains were 2.91- +/- 0.17- to
      8.12- +/- 0.37-fold higher. The transcription levels of the corresponding enzymes
      in the engineered strains were 2.85- +/- 0.19- to 8.07- +/- 0.63-fold higher than
      those in the wild type. The coexpression of GDH and MDH increased the PA titer
      from 26.95 +/- 1.21 g/liter in wild-type P. jensenii to 39.43 +/- 1.90 g/liter in
      the engineered strains. This study identified the key metabolic nodes limiting PA
      overproduction in P. jensenii and further improved PA titers via the coexpression
      of GDH and MDH, making the engineered P. jensenii strain a potential industrial
      producer of PA. 

PMID- 25595756
TI  - Involvement of the cytochrome P450 system EthBAD in the N-deethoxymethylation of
      acetochlor by Rhodococcus sp. strain T3-1.
AB  - Acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide] is a
      widely applied herbicide with potential carcinogenic properties. N
      Deethoxymethylation is the key step in acetochlor biodegradation. N
      Deethoxymethylase is a multicomponent enzyme that catalyzes the conversion of
      acetochlor to 2'-methyl-6'-ethyl-2-chloroacetanilide (CMEPA). Fast detection of
      CMEPA by a two-enzyme (N-deethoxymethylase-amide hydrolase) system was
      established in this research. Based on the fast detection method, a three
      component enzyme was purified from Rhodococcus sp. strain T3-1 using ammonium
      sulfate precipitation and hydrophobic interaction chromatography. The molecular
      masses of the components of the purified enzyme were estimated to be 45, 43, and
      11 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
      Based on the results of peptide mass fingerprint analysis, acetochlor N
      deethoxymethylase was identified as a cytochrome P450 system, composed of a
      cytochrome P450 oxygenase (43-kDa component; EthB), a ferredoxin (45 kDa; EthA),
      and a reductase (11 kDa; EthD), that is involved in the degradation of methyl
      tert-butyl ether. The gene cluster ethABCD was cloned by PCR amplification and
      expressed in Escherichia coli BL21(DE3). Resting cells of a recombinant E. coli
      strain showed deethoxymethylation activity against acetochlor. Subcloning of
      ethABCD showed that ethABD expressed in E. coli BL21(DE3) has the activity of
      acetochlor N-deethoxymethylase and is capable of converting acetochlor to CMEPA. 

PMID- 25595757
TI  - Reduction of the temperature sensitivity of Halomonas hydrothermalis by iron
      starvation combined with microaerobic conditions.
AB  - The limits to biological processes on Earth are determined by physicochemical
      parameters, such as extremes of temperature and low water availability. Research
      into microbial extremophiles has enhanced our understanding of the biophysical
      boundaries which define the biosphere. However, there remains a paucity of
      information on the degree to which rates of microbial multiplication within
      extreme environments are determined by the availability of specific chemical
      elements. Here, we show that iron availability and the composition of the gaseous
      phase (aerobic versus microaerobic) determine the susceptibility of a marine
      bacterium, Halomonas hydrothermalis, to suboptimal and elevated temperature and
      salinity by impacting rates of cell division (but not viability). In particular,
      iron starvation combined with microaerobic conditions (5% [vol/vol] O2, 10%
      [vol/vol] CO2, reduced pH) reduced sensitivity to temperature across the 13
      degrees C range tested. These data demonstrate that nutrient limitation interacts
      with physicochemical parameters to determine biological permissiveness for
      extreme environments. The interplay between resource availability and stress
      tolerance, therefore, may shape the distribution and ecology of microorganisms
      within Earth's biosphere. 

PMID- 25595758
TI  - Retention in treated wastewater affects survival and deposition of Staphylococcus
      aureus and Escherichia coli in sand columns.
AB  - The fate and transport of pathogenic bacteria from wastewater treatment
      facilities in the Earth's subsurface have attracted extensive concern over recent
      decades, while the impact of treated-wastewater chemistry on bacterial viability
      and transport behavior remains unclear. The influence of retention time in
      effluent from a full-scale municipal wastewater treatment plant on the survival
      and deposition of Staphylococcus aureus and Escherichia coli strains in sand
      columns was investigated in this paper. In comparison to the bacteria cultivated
      in nutrient-rich growth media, retention in treated wastewater significantly
      reduced the viability of all strains. Bacterial surface properties, e.g., zeta
      potential, hydrophobicity, and surface charges, varied dramatically in treated
      wastewater, though no universal trend was found for different strains. Retention
      in treated wastewater effluent resulted in changes in bacterial deposition in
      sand columns. Longer retention periods in treated wastewater decreased bacterial
      deposition rates for the strains evaluated and elevated the transport potential
      in sand columns. We suggest that the wastewater quality should be taken into
      account in estimating the fate of pathogenic bacteria discharged from wastewater
      treatment facilities and the risks they pose in the aquatic environment. 

PMID- 25595760
TI  - Listeria phage and phage tail induction triggered by components of bacterial
      growth media (phosphate, LiCl, nalidixic acid, and acriflavine).
AB  - The detection of Listeria monocytogenes from food is currently carried out using
      a double enrichment. For the ISO methodology, this double enrichment is performed
      using half-Fraser and Fraser broths, in which the overgrowth of L. innocua can
      occur in samples where both species are present. In this study, we analyzed the
      induction of phages and phage tails of Listeria spp. in these media and in two
      brain heart infusion (BHI) broths (BHIM [bioMerieux] and BHIK [Biokar]) to
      identify putative effectors. It appears that Na2HPO4 at concentrations ranging
      from 1 to 40 g/liter with an initial pH of 7.5 can induce phage or phage tail
      production of Listeria spp., especially with 10 g/liter of Na2HPO4 and a pH of
      7.5, conditions present in half-Fraser and Fraser broths. Exposure to LiCl in
      BHIM (18 to 21 g/liter) can also induce phage and phage tail release, but in half
      Fraser and Fraser broths, the concentration of LiCl is much lower (3 g/liter).
      Low phage titers were induced by acriflavine and/or nalidixic acid. We also show
      that the production of phages and phage tails can occur in half-Fraser and Fraser
      broths. This study points out that induction of phages and phage tails could be
      triggered by compounds present in enrichment media. This could lead to a false
      negative result for the detection of L. monocytogenes in food products. 

PMID- 25595759
TI  - Rhizosphere microbial community composition affects cadmium and zinc uptake by
      the metal-hyperaccumulating plant Arabidopsis halleri.
AB  - The remediation of metal-contaminated soils by phytoextraction depends on plant
      growth and plant metal accessibility. Soil microorganisms can affect the
      accumulation of metals by plants either by directly or indirectly stimulating
      plant growth and activity or by (im)mobilizing and/or complexing metals.
      Understanding the intricate interplay of metal-accumulating plants with their
      rhizosphere microbiome is an important step toward the application and
      optimization of phytoremediation. We compared the effects of a "native" and a
      strongly disturbed (gamma-irradiated) soil microbial communities on cadmium and
      zinc accumulation by the plant Arabidopsis halleri in soil microcosm experiments.
      A. halleri accumulated 100% more cadmium and 15% more zinc when grown on the
      untreated than on the gamma-irradiated soil. Gamma irradiation affected neither
      plant growth nor the 1 M HCl-extractable metal content of the soil. However, it
      strongly altered the soil microbial community composition and overall cell
      numbers. Pyrosequencing of 16S rRNA gene amplicons of DNA extracted from
      rhizosphere samples of A. halleri identified microbial taxa (Lysobacter,
      Streptomyces, Agromyces, Nitrospira, "Candidatus Chloracidobacterium") of higher
      relative sequence abundance in the rhizospheres of A. halleri plants grown on
      untreated than on gamma-irradiated soil, leading to hypotheses on their potential
      effect on plant metal uptake. However, further experimental evidence is required,
      and wherefore we discuss different mechanisms of interaction of A. halleri with
      its rhizosphere microbiome that might have directly or indirectly affected plant
      metal accumulation. Deciphering the complex interactions between A. halleri and
      individual microbial taxa will help to further develop soil metal phytoextraction
      as an efficient and sustainable remediation strategy. 

PMID- 25595761
TI  - Counting viruses and bacteria in photosynthetic microbial mats.
AB  - Viral abundances in benthic environments are the highest found in aquatic
      systems. Photosynthetic microbial mats represent benthic environments with high
      microbial activity and possibly high viral densities, yet viral abundances have
      not been examined in such systems. Existing extraction procedures typically used
      in benthic viral ecology were applied to the complex matrix of microbial mats but
      were found to inefficiently extract viruses. Here, we present a method for
      extraction and quantification of viruses from photosynthetic microbial mats using
      epifluorescence microscopy (EFM) and flow cytometry (FCM). A combination of EDTA
      addition, probe sonication, and enzyme treatment applied to a glutaraldehyde
      fixed sample resulted in a substantially higher viral (5- to 33-fold) extraction
      efficiency and reduced background noise compared to previously published methods.
      Using this method, it was found that in general, intertidal photosynthetic
      microbial mats harbor very high viral abundances (2.8 * 10(10) +/- 0.3 * 10(10)
      g(-1)) compared with benthic habitats (10(7) to 10(9) g(-1)). This procedure also
      showed 4.5- and 4-fold-increased efficacies of extraction of viruses and
      bacteria, respectively, from intertidal sediments, allowing a single method to be
      used for the microbial mat and underlying sediment. 

PMID- 25595763
TI  - Xylan utilization regulon in Xanthomonas citri pv. citri Strain 306: gene
      expression and utilization of oligoxylosides.
AB  - Xanthomonas citri pv. citri strain 306 (Xcc306), a causative agent of citrus
      canker, produces endoxylanases that catalyze the depolymerization of cell wall
      associated xylans. In the sequenced genomes of all plant-pathogenic xanthomonads,
      genes encoding xylanolytic enzymes are clustered in three adjacent operons. In
      Xcc306, these consecutive operons contain genes encoding the glycoside hydrolase
      family 10 (GH10) endoxylanases Xyn10A and Xyn10C, the agu67 gene, encoding a GH67
      alpha-glucuronidase (Agu67), the xyn43E gene, encoding a putative GH43 alpha-l
      arabinofuranosidase, and the xyn43F gene, encoding a putative beta-xylosidase.
      Recombinant Xyn10A and Xyn10C convert polymeric 4-O-methylglucuronoxylan (MeGXn)
      to oligoxylosides methylglucuronoxylotriose (MeGX3), xylotriose (X3), and
      xylobiose (X2). Xcc306 completely utilizes MeGXn predigested with Xyn10A or
      Xyn10C but shows little utilization of MeGXn. Xcc306 with a deletion in the gene
      encoding alpha-glucuronidase (Xcc306 Deltaagu67) will not utilize MeGX3 for
      growth, demonstrating the role of Agu67 in the complete utilization of GH10
      digested MeGXn. Preferential growth on oligoxylosides compared to growth on
      polymeric MeGXn indicates that GH10 xylanases, either secreted by Xcc306 in
      planta or produced by the plant host, generate oligoxylosides that are processed
      by Xyn10 xylanases and Agu67 residing in the periplasm. Coordinate induction by
      oligoxylosides of xyn10, agu67, cirA, the tonB receptor, and other genes within
      these three operons indicates that they constitute a regulon that is responsive
      to the oligoxylosides generated by the action of Xcc306 GH10 xylanases on MeGXn.
      The combined expression of genes in this regulon may allow scavenging of
      oligoxylosides derived from cell wall deconstruction, thereby contributing to the
      tissue colonization and/or survival of Xcc306 and, ultimately, to plant disease. 

PMID- 25595764
TI  - Biogeography of heterotrophic flagellate populations indicates the presence of
      generalist and specialist taxa in the Arctic Ocean.
AB  - Heterotrophic marine flagellates (HF) are ubiquitous in the world's oceans and
      represented in nearly all branches of the domain Eukaryota. However, the factors
      determining distributions of major taxonomic groups are poorly known. The Arctic
      Ocean is a good model environment for examining the distribution of functionally
      similar but phylogenetically diverse HF because the physical oceanography and
      annual ice cycles result in distinct environments that could select for microbial
      communities or favor specific taxa. We reanalyzed new and previously published
      high-throughput sequencing data from multiple studies in the Arctic Ocean to
      identify broad patterns in the distribution of individual taxa. HF accounted for
      fewer than 2% to over one-half of the reads from the water column and for up to
      60% of reads from ice, which was dominated by Cryothecomonas. In the water
      column, many HF phylotypes belonging to Telonemia and Picozoa, uncultured marine
      stramenopiles (MAST), and choanoflagellates were geographically widely
      distributed. However, for two groups in particular, Telonemia and Cryothecomonas,
      some species level taxa showed more restricted distributions. For example,
      several phylotypes of Telonemia favored open waters with lower nutrients such as
      the Canada Basin and offshore of the Mackenzie Shelf. In summary, we found that
      while some Arctic HF were successful over a range of conditions, others could be
      specialists that occur under particular conditions. We conclude that tracking
      species level diversity in HF not only is feasible but also provides a potential
      tool for understanding the responses of marine microbial ecosystems to rapidly
      changing ice regimes. 

PMID- 25595762
TI  - Identification and characterization of carboxyl esterases of gill chamber
      associated microbiota in the deep-sea shrimp Rimicaris exoculata by using
      functional metagenomics.
AB  - The shrimp Rimicaris exoculata dominates the fauna in deep-sea hydrothermal vent
      sites along the Mid-Atlantic Ridge (depth, 2,320 m). Here, we identified and
      biochemically characterized three carboxyl esterases from microbial communities
      inhabiting the R. exoculata gill that were isolated by naive screens of a gill
      chamber metagenomic library. These proteins exhibit low to moderate identity to
      known esterase sequences (<=52%) and to each other (11.9 to 63.7%) and appear to
      have originated from unknown species or from genera of Proteobacteria related to
      Thiothrix/Leucothrix (MGS-RG1/RG2) and to the Rhodobacteraceae group (MGS-RG3). A
      library of 131 esters and 31 additional esterase/lipase preparations was used to
      evaluate the activity profiles of these enzymes. All 3 of these enzymes had
      greater esterase than lipase activity and exhibited specific activities with
      ester substrates (<=356 U mg(-1)) in the range of similar enzymes. MGS-RG3 was
      inhibited by salts and pressure and had a low optimal temperature (30 degrees C),
      and its substrate profile clustered within a group of low-activity and substrate
      restricted marine enzymes. In contrast, MGS-RG1 and MGS-RG2 were most active at
      45 to 50 degrees C and were salt activated and barotolerant. They also exhibited
      wider substrate profiles that were close to those of highly active promiscuous
      enzymes from a marine hydrothermal vent (MGS-RG2) and from a cold brackish lake
      (MGS-RG1). The data presented are discussed in the context of promoting the
      examination of enzyme activities of taxa found in habitats that have been
      neglected for enzyme prospecting; the enzymes found in these taxa may reflect
      distinct habitat-specific adaptations and may constitute new sources of rare
      reaction specificities. 

PMID- 25595765
TI  - Profiling microbial communities in manganese remediation systems treating coal
      mine drainage.
AB  - Water discharging from abandoned coal mines can contain extremely high manganese
      levels. Removing this metal is an ongoing challenge. Passive Mn(II) removal beds
      (MRBs) contain microorganisms that oxidize soluble Mn(II) to insoluble Mn(III/IV)
      minerals, but system performance is unpredictable. Using amplicon pyrosequencing,
      we profiled the bacterial, fungal, algal, and archaeal communities in four MRBs,
      performing at different levels, in Pennsylvania to determine whether they
      differed among MRBs and from surrounding soil and to establish the relative
      abundance of known Mn(II) oxidizers. Archaea were not detected; PCRs with
      archaeal primers returned only nontarget bacterial sequences. Fungal taxonomic
      profiles differed starkly between sites that remove the majority of influent Mn
      and those that do not, with the former being dominated by Ascomycota (mostly
      Dothideomycetes) and the latter by Basidiomycota (almost entirely
      Agaricomycetes). Taxonomic profiles for the other groups did not differ
      significantly between MRBs, but operational taxonomic unit-based analyses showed
      significant clustering by MRB with all three groups (P < 0.05). Soil samples
      clustered separately from MRBs in all groups except fungi, whose soil samples
      clustered loosely with their respective MRB. Known Mn(II) oxidizers accounted for
      a minor proportion of bacterial sequences (up to 0.20%) but a greater proportion
      of fungal sequences (up to 14.78%). MRB communities are more diverse than
      previously thought, and more organisms may be capable of Mn(II) oxidation than
      are currently known. 

PMID- 25595766
TI  - Novel hypovirulence-associated RNA mycovirus in the plant-pathogenic fungus
      Botrytis cinerea: molecular and biological characterization.
AB  - Botrytis cinerea is a pathogenic fungus causing gray mold on numerous
      economically important crops and ornamental plants. This study was conducted to
      characterize the biological and molecular features of a novel RNA mycovirus,
      Botrytis cinerea RNA virus 1 (BcRV1), in the hypovirulent strain BerBc-1 of B.
      cinerea. The genome of BcRV1 is 8,952 bp long with two putative overlapped open
      reading frames (ORFs), ORF1 and ORF2, coding for a hypothetical polypeptide (P1)
      and RNA-dependent RNA polymerase (RdRp), respectively. A -1 frameshifting region
      (designated the KNOT element) containing a shifty heptamer, a heptanucleotide
      spacer, and an H-type pseudoknot was predicted in the junction region of ORF1 and
      ORF2. The -1 frameshifting role of the KNOT element was experimentally confirmed
      through determination of the production of the fusion protein red fluorescent
      protein (RFP)-green fluorescent protein (GFP) by the plasmid containing the
      construct dsRed-KNOT-eGFP in Escherichia coli. BcRV1 belongs to a taxonomically
      unassigned double-stranded RNA (dsRNA) mycovirus group. It is closely related to
      grapevine-associated totivirus 2 and Sclerotinia sclerotiorum nonsegmented virus
      L. BcRV1 in strain BerBc-1 was found capable of being transmitted vertically
      through macroconidia and horizontally to other B. cinerea strains through hyphal
      contact. The presence of BcRV1 was found to be positively correlated with
      hypovirulence in B. cinerea, with the attenuation effects of BcRV1 on mycelial
      growth and pathogenicity being greatly affected by the accumulation level of
      BcRV1. 

PMID- 25595767
TI  - Effects of norspermidine and spermidine on biofilm formation by potentially
      pathogenic Escherichia coli and Salmonella enterica wild-type strains.
AB  - Polyamines are present in all living cells. In bacteria, polyamines are involved
      in a variety of functions, including biofilm formation, thus indicating that
      polyamines may have potential in the control of unwanted biofilm. In the present
      study, the effects of the polyamines norspermidine and spermidine on biofilms of
      10 potentially pathogenic wild-type strains of Escherichia coli serotype O103:H2,
      Salmonella enterica subsp. enterica serovar Typhimurium, and S. enterica serovar
      Agona were investigated. We found that exogenously supplied norspermidine and
      spermidine did not mediate disassembly of preformed biofilm of any of the E. coli
      and S. enterica strains. However, the polyamines did affect biofilm production.
      Interestingly, the two species reacted differently to the polyamines. Both
      polyamines reduced the amount of biofilm formed by E. coli but tended to increase
      biofilm formation by S. enterica. Whether the effects observed were due to the
      polyamines specifically targeting biofilm formation, being toxic for the cells,
      or maybe a combination of the two, is not known. However, there were no
      indications that the effect was mediated through binding to exopolysaccharides,
      as earlier suggested for E. coli. Our results indicate that norspermidine and
      spermidine do not have potential as inhibitors of S. enterica biofilm.
      Furthermore, we found that the commercial polyamines used contributed to the
      higher pH of the test medium. Failure to acknowledge and control this important
      phenomenon may lead to misinterpretation of the results. 

PMID- 25595769
TI  - Effective trapping of fruit flies with cultures of metabolically modified acetic
      acid bacteria.
AB  - Acetoin in vinegar is an attractant to fruit flies when combined with acetic
      acid. To make vinegar more effective in attracting fruit flies with increased
      acetoin production, Komagataeibacter europaeus KGMA0119 was modified by specific
      gene disruption of the acetohydroxyacid isomeroreductase gene (ilvC). A
      previously constructed mutant lacking the putative ligand-sensing region in the
      leucine-responsive regulatory protein (KeLrp, encoded by Kelrp) was also used.
      The ilvC and Kelrp disruptants (KGMA5511 and KGMA7203, respectively) produced
      greater amounts of acetoin (KGMA5511, 0.11%; KGMA7203, 0.13%) than the wild-type
      strain KGMA0119 (0.069%). KGMA7203 produced a trace amount of isobutyric acid
      (0.007%), but the other strains did not. These strains produced approximately
      equal amounts of acetic acid (0.7%). The efficiency of fruit fly attraction was
      investigated with cultured Drosophila melanogaster. D. melanogaster flies
      (approximately 1,500) were released inside a cage (2.5 m by 2.5 m by 1.5 m) and
      were trapped with a device containing vinegar and a sticky sheet. The flies
      trapped on the sticky sheet were counted. The cell-free supernatant from KGMA7203
      culture captured significantly more flies (19.36 to 36.96% of released flies)
      than did KGMA0119 (3.25 to 11.40%) and KGMA5511 (6.87 to 21.50%) cultures.
      Contrastingly, a 0.7% acetic acid solution containing acetoin (0.13%) and
      isobutyric acid (0.007%), which mimicked the KGMA7203 supernatant, captured
      significantly fewer flies (0.88 to 4.57%). Furthermore, the KGMA0119 supernatant
      with additional acetoin (0.13%) and isobutyric acid (0.007%) captured slightly
      more flies than the original KGMA0119 supernatant but fewer than the KGMA7203
      supernatant, suggesting that the synergistic effects of acetic acid, acetoin,
      isobutyric acid, and unidentified metabolites achieved the efficient fly trapping
      of the KGMA7203 supernatant. 

PMID- 25595768
TI  - Thermal and solvent stress cross-tolerance conferred to Corynebacterium
      glutamicum by adaptive laboratory evolution.
AB  - Reinforcing microbial thermotolerance is a strategy to enable fermentation with
      flexible temperature settings and thereby to save cooling costs. Here, we report
      on adaptive laboratory evolution (ALE) of the amino acid-producing bacterium
      Corynebacterium glutamicum under thermal stress. After 65 days of serial passage
      of the transgenic strain GLY3, in which the glycolytic pathway is optimized for
      alanine production under oxygen deprivation, three strains adapted to
      supraoptimal temperatures were isolated, and all the mutations they acquired were
      identified by whole-genome resequencing. Of the 21 mutations common to the three
      strains, one large deletion and two missense mutations were found to promote
      growth of the parental strain under thermal stress. Additive effects on
      thermotolerance were observed among these mutations, and the combination of the
      deletion with the missense mutation on otsA, encoding a trehalose-6-phosphate
      synthase, allowed the parental strain to overcome the upper limit of growth
      temperature. Surprisingly, the three evolved strains acquired cross-tolerance for
      isobutanol, which turned out to be partly attributable to the genomic deletion
      associated with the enhanced thermotolerance. The deletion involved loss of two
      transgenes, pfk and pyk, encoding the glycolytic enzymes, in addition to six
      native genes, and elimination of the transgenes, but not the native genes, was
      shown to account for the positive effects on thermal and solvent stress
      tolerance, implying a link between energy-producing metabolism and bacterial
      stress tolerance. Overall, the present study provides evidence that ALE can be a
      powerful tool to refine the phenotype of C. glutamicum and to investigate the
      molecular bases of stress tolerance. 

PMID- 25595770
TI  - Metabolic engineering of Corynebacterium glutamicum for methanol metabolism.
AB  - Methanol is already an important carbon feedstock in the chemical industry, but
      it has found only limited application in biotechnological production processes.
      This can be mostly attributed to the inability of most microbial platform
      organisms to utilize methanol as a carbon and energy source. With the aim to turn
      methanol into a suitable feedstock for microbial production processes, we
      engineered the industrially important but nonmethylotrophic bacterium
      Corynebacterium glutamicum toward the utilization of methanol as an auxiliary
      carbon source in a sugar-based medium. Initial oxidation of methanol to
      formaldehyde was achieved by heterologous expression of a methanol dehydrogenase
      from Bacillus methanolicus, whereas assimilation of formaldehyde was realized by
      implementing the two key enzymes of the ribulose monophosphate pathway of
      Bacillus subtilis: 3-hexulose-6-phosphate synthase and 6-phospho-3
      hexuloisomerase. The recombinant C. glutamicum strain showed an average methanol
      consumption rate of 1.7 +/- 0.3 mM/h (mean +/- standard deviation) in a glucose
      methanol medium, and the culture grew to a higher cell density than in medium
      without methanol. In addition, [(13)C]methanol-labeling experiments revealed
      labeling fractions of 3 to 10% in the m + 1 mass isotopomers of various
      intracellular metabolites. In the background of a C. glutamicum Deltaald
      DeltaadhE mutant being strongly impaired in its ability to oxidize formaldehyde
      to CO2, the m + 1 labeling of these intermediates was increased (8 to 25%),
      pointing toward higher formaldehyde assimilation capabilities of this strain. The
      engineered C. glutamicum strains represent a promising starting point for the
      development of sugar-based biotechnological production processes using methanol
      as an auxiliary substrate. 

PMID- 25595771
TI  - Elizabethkingia anophelis: molecular manipulation and interactions with mosquito
      hosts.
AB  - Flavobacteria (members of the family Flavobacteriaceae) dominate the bacterial
      community in the Anopheles mosquito midgut. One such commensal, Elizabethkingia
      anophelis, is closely associated with Anopheles mosquitoes through transstadial
      persistence (i.e., from one life stage to the next); these and other properties
      favor its development for paratransgenic applications in control of malaria
      parasite transmission. However, the physiological requirements of E. anophelis
      have not been investigated, nor has its capacity to perpetuate despite digestion
      pressure in the gut been quantified. To this end, we first developed techniques
      for genetic manipulation of E. anophelis, including selectable markers, reporter
      systems (green fluorescent protein [GFP] and NanoLuc), and transposons that
      function in E. anophelis. A flavobacterial expression system based on the
      promoter PompA was integrated into the E. anophelis chromosome and showed strong
      promoter activity to drive GFP and NanoLuc reporter production. Introduced, GFP
      tagged E. anophelis associated with mosquitoes at successive developmental stages
      and propagated in Anopheles gambiae and Anopheles stephensi but not in Aedes
      triseriatus mosquitoes. Feeding NanoLuc-tagged cells to A. gambiae and A.
      stephensi in the larval stage led to infection rates of 71% and 82%,
      respectively. In contrast, a very low infection rate (3%) was detected in Aedes
      triseriatus mosquitoes under the same conditions. Of the initial E. anophelis
      cells provided to larvae, 23%, 71%, and 85% were digested in A. stephensi, A.
      gambiae, and Aedes triseriatus, respectively, demonstrating that E. anophelis
      adapted to various mosquito midgut environments differently. Bacterial cell
      growth increased up to 3-fold when arginine was supplemented in the defined
      medium. Furthermore, the number of NanoLuc-tagged cells in A. stephensi
      significantly increased when arginine was added to a sugar diet, showing it to be
      an important amino acid for E. anophelis. Animal erythrocytes promoted E.
      anophelis growth in vivo and in vitro, indicating that this bacterium could
      obtain nutrients by participating in erythrocyte lysis in the mosquito midgut. 

PMID- 25595772
TI  - Reduced Infectivity in cattle for an outer membrane protein mutant of Anaplasma
      marginale.
AB  - Anaplasma marginale is the causative agent of anaplasmosis in cattle. Transposon
      mutagenesis of this pathogen using the Himar1 system resulted in the isolation of
      an omp10 operon insertional mutant referred to as the omp10::himar1 mutant. The
      work presented here evaluated if this mutant had morphological and/or growth rate
      defects compared to wild-type A. marginale. Results showed that the morphology,
      developmental cycle, and growth in tick and mammalian cell cultures are similar
      for the mutant and the wild type. Tick transmission experiments established that
      tick infection levels with the mutant were similar to those with wild-type A.
      marginale and that infected ticks successfully infected cattle. However, this
      mutant exhibited reduced infectivity and growth in cattle. The possibility of
      transforming A. marginale by transposon mutagenesis coupled with in vitro and in
      vivo assessment of altered phenotypes can aid in the identification of genes
      associated with virulence. The isolation of deliberately attenuated organisms
      that can be evaluated in their natural biological system is an important advance
      for the rational design of vaccines against this species. 

PMID- 25595774
TI  - Cutting Edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1.
AB  - Triggering receptor expressed on myeloid cells (TREM)-1 is an orphan receptor
      implicated in innate immune activation. Inhibition of TREM-1 reduces sepsis in
      mouse models, suggesting a role for it in immune responses triggered by bacteria.
      However, the absence of an identified ligand has hampered a full understanding of
      TREM-1 function. We identified complexes between peptidoglycan recognition
      protein 1 (PGLYRP1) and bacterially derived peptidoglycan that constitute a
      potent ligand capable of binding TREM-1 and inducing known TREM-1 functions.
      Interestingly, multimerization of PGLYRP1 bypassed the need for peptidoglycan in
      TREM-1 activation, demonstrating that the PGLYRP1/TREM-1 axis can be activated in
      the absence of bacterial products. The role for PGLYRP1 as a TREM-1 activator
      provides a new mechanism by which bacteria can trigger myeloid cells, linking two
      known, but previously unrelated, pathways in innate immunity. 

PMID- 25595773
TI  - Bacteriophage PBC1 and its endolysin as an antimicrobial agent against Bacillus
      cereus.
AB  - Bacillus cereus is an opportunistic human pathogen responsible for food poisoning
      and other, nongastrointestinal infections. Due to the emergence of multidrug
      resistant B. cereus strains, the demand for alternative therapeutic options is
      increasing. To address these problems, we isolated and characterized a
      Siphoviridae virulent phage, PBC1, and its lytic enzymes. PBC1 showed a very
      narrow host range, infecting only 1 of 22 B. cereus strains. Phylogenetic
      analysis based on the major capsid protein revealed that PBC1 is more closely
      related to the Bacillus clarkii phage BCJA1c and phages of lactic acid bacteria
      than to the phages infecting B. cereus. Whole-genome comparison showed that the
      late-gene region, including the terminase gene, structural genes, and holin gene
      of PBC1, is similar to that from B. cereus temperate phage 250, whereas their
      endolysins are different. Compared to the extreme host specificity of PBC1, its
      endolysin, LysPBC1, showed a much broader lytic spectrum, albeit limited to the
      genus Bacillus. The catalytic domain of LysPBC1 when expressed alone also showed
      Bacillus-specific lytic activity, which was lower against the B. cereus group but
      higher against the Bacillus subtilis group than the full-length protein. Taken
      together, these results suggest that the virulent phage PBC1 is a useful
      component of a phage cocktail to control B. cereus, even with its exceptionally
      narrow host range, as it can kill a strain of B. cereus that is not killed by
      other phages, and that LysPBC1 is an alternative biocontrol agent against B.
      cereus. 

PMID- 25595776
TI  - Cancer-associated oxidoreductase ERO1-alpha drives the production of tumor
      promoting myeloid-derived suppressor cells via oxidative protein folding.
AB  - Endoplasmic reticulum disulfide oxidase ERO1-alpha plays a role in the formation
      of disulfide bonds in collaboration with protein disulfide isomerase. Disulfide
      bond formation is required for the proper conformation and function of secreted
      and cell surface proteins. We found that ERO1-alpha was overexpressed in a
      variety of tumor types; therefore, we examined its role in tumor growth. In
      BALB/c mice, knockdown of ERO1-alpha within 4T1 mouse mammary gland cancer (KD)
      cells caused retardation of in vivo tumor growth compared with tumor growth of
      scrambled control (SCR) cells. In contrast, when ERO1-alpha-overexpressed 4T1
      (OE) cells were compared with mock control cells, OE cells showed augmented tumor
      growth. However, differences in tumor growth were not observed among four groups
      of nude mice, suggesting that expression of ERO1-alpha diminished antitumor
      immunity. We observed dense peritumoral granulocytic infiltrates in tumors of
      wild-type 4T1 and SCR cells but not KD cells, and these cells were identified as
      polymorphonuclear myeloid-derived suppressor cells (MDSCs). In addition,
      production of G-CSF and CXCL1/2, which have intramolecular disulfide bonds, from
      KD cells was significantly decreased compared with that from SCR cells. In
      contrast, OE cells produced a larger amount of these molecules than did mock
      cells. These changes were regulated at the posttranscriptional level. These
      results suggest that overexpression of ERO1-alpha in the tumor inhibits the T
      cell response by recruiting polymorphonuclear MDSCs via regulation of MDSC-prone
      cytokines and chemokines. 

PMID- 25595775
TI  - beta-Defensin 1 plays a role in acute mucosal defense against Candida albicans.
AB  - Candida is an opportunistic fungal pathogen that colonizes the mucosal tract of
      humans. Pathogenic infection occurs in the presence of conditions causing
      perturbations to the commensal microbiota or host immunity. Early innate immune
      responses by the epithelium, including antimicrobial peptides (AMPs) and
      cytokines, are critical for protection against overgrowth. Reduced salivary AMP
      levels are associated with oral Candida infection, and certain AMPs, including
      human beta-defensins 1-3, have direct fungicidal activity. In this study, we
      demonstrate that murine beta-defensin 1 (mBD1) is important for control of early
      mucosal Candida infection and plays a critical role in the induction of innate
      inflammatory mediators. Mice deficient in mBD1, as compared with wild-type mice,
      exhibit elevated oral and systemic fungal burdens. Neutrophil infiltration to the
      sites of mucosal Candida invasion, an important step in limiting fungal
      infection, is significantly reduced in mBD1-deficient mice. These mice also
      exhibit defects in the expression of other AMPs, including mBD2 and mBD4, which
      may have direct anti-Candida activity. We also show that mBD1 deficiency impacts
      the production of important antifungal inflammatory mediators, including IL
      1beta, IL-6, KC, and IL-17. Collectively, these studies demonstrate a role for
      the mBD1 peptide in early control of Candida infection in a murine model of
      mucosal candidiasis, as well as in the modulation of host immunity through
      augmentation of leukocyte infiltration and inflammatory gene regulation. 

PMID- 25595777
TI  - Cutting Edge: the BTLA-HVEM regulatory pathway interferes with protective
      immunity to intestinal Helminth infection.
AB  - Helminths exploit intrinsic regulatory pathways of the mammalian immune system to
      dampen the immune response directed against them. In this article, we show that
      infection with the parasitic nematode Strongyloides ratti induced upregulation of
      the coinhibitory receptor B and T lymphocyte attenuator (BTLA) predominantly on
      CD4(+) T cells but also on a small fraction of innate leukocytes. Deficiency of
      either BTLA or its ligand herpes virus entry mediator (HVEM) resulted in reduced
      numbers of parasitic adults in the small intestine and reduced larval output
      throughout infection. Reduced parasite burden in BTLA- and HVEM-deficient mice
      was accompanied by accelerated degranulation of mucosal mast cells and increased
      Ag-specific production of the mast cell-activating cytokine IL-9. Our combined
      results support a model whereby BTLA on CD4(+) T cells and additional innate
      leukocytes is triggered by HVEM and delivers negative signals into BTLA(+) cells,
      thereby interfering with the protective immune response to this intestinal
      parasite. 

PMID- 25595779
TI  - CX3CR1 reduces kidney fibrosis by inhibiting local proliferation of profibrotic
      macrophages.
AB  - A dense network of macrophages and dendritic cells (DC) expressing the chemokine
      receptor CX3CR1 populates most tissues. We recently reported that CX3CR1
      regulates the abundance of CD11c(+) DC in the kidney and thereby promotes renal
      inflammation in glomerulonephritis. Given that chronic inflammation usually
      causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal
      fibrosis. However, when we tested this hypothesis using the DC-independent murine
      fibrosis model of unilateral ureteral obstruction, kidney fibrosis was
      unexpectedly more severe, despite less intrarenal inflammation. Two-photon
      imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more
      motile Ly6C/Gr-1(+) macrophages. Flow cytometry verified that renal macrophages
      were more abundant in the absence of CX3CR1 and produced more of the key
      profibrotic mediator, TGF-beta. Macrophages accumulated because of higher
      intrarenal proliferation, despite reduced monocyte recruitment and higher signs
      of apoptosis within the kidney. These findings support the theory that tissue
      macrophage numbers are regulated through local proliferation and identify CX3CR1
      as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided
      in DC-independent inflammatory diseases because it may promote fibrosis. 

PMID- 25595778
TI  - ShcA regulates late stages of T cell development and peripheral CD4+ T cell
      numbers.
AB  - T cell development in the thymus is a highly regulated process that critically
      depends upon productive signaling via the preTCR at the beta-selection stage, as
      well as via the TCR for selection from the CD4(+)CD8(+) double-positive stage to
      the CD4 or CD8 single-positive stage. ShcA is an adapter protein expressed in
      thymocytes, and it is required for productive signaling through the preTCR, with
      impaired signaling via ShcA leading to a developmental block at the beta
      selection checkpoint. However, the role of ShcA in subsequent stages of T cell
      development has not been addressed. In this study, we generated transgenic mice
      (CD4-Cre/ShcFFF mice) that specifically express a phosphorylation-defective
      dominant-negative ShcA mutant (ShcFFF) in late T cell development. Thymocytes in
      CD4-Cre/ShcFFF mice progressed normally through the beta-selection checkpoint,
      but displayed a significant reduction in the numbers of single-positive CD4(+)
      and CD8(+) thymocytes. Furthermore, CD4-Cre/ShcFFF mice, when bred with
      transgenic TCR mouse strains, had impaired signaling through the transgenic TCRs.
      Consistent with defective progression to the single-positive stage, CD4
      Cre/ShcFFF mice also had significant peripheral lymphopenia. Moreover, these CD4
      Cre/ShcFFF mice develop attenuated disease in CD4(+) T cell-dependent
      experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
      Collectively, these data identify an important role for the adapter protein ShcA
      in later stages of thymic T cell development and in peripheral T cell-dependent
      events. 

PMID- 25595780
TI  - Activation-specific metabolic requirements for NK Cell IFN-gamma production.
AB  - There has been increasing recognition of the importance of cellular metabolism
      and metabolic substrates for the function and differentiation of immune cells. In
      this study, for the first time to our knowledge, we investigate the metabolic
      requirements for production of IFN-gamma by freshly isolated NK cells. Primary
      murine NK cells mainly use mitochondrial oxidative phosphorylation at rest and
      with short-term activation. Remarkably, we discovered significant differences in
      the metabolic requirements of murine NK cell IFN-gamma production depending upon
      the activation signal. Stimulation of NK cell IFN-gamma production was
      independent of glycolysis or mitochondrial oxidative phosphorylation when cells
      were activated with IL-12 plus IL-18. By contrast, stimulation via activating NK
      receptors required glucose-driven oxidative phosphorylation. Prolonged treatment
      with high-dose, but not low-dose, IL-15 eliminated the metabolic requirement for
      receptor stimulation. In summary, this study demonstrates that metabolism
      provides an essential second signal for induction of IFN-gamma production by
      activating NK cell receptors that can be reversed with prolonged high-dose IL-15
      treatment. 

PMID- 25595781
TI  - IRAK-M promotes alternative macrophage activation and fibroproliferation in
      bleomycin-induced lung injury.
AB  - Idiopathic pulmonary fibrosis is a devastating lung disease characterized by
      inflammation and the development of excessive extracellular matrix deposition.
      Currently, there are only limited therapeutic intervenes to offer patients
      diagnosed with pulmonary fibrosis. Although previous studies focused on
      structural cells in promoting fibrosis, our study assessed the contribution of
      macrophages. Recently, TLR signaling has been identified as a regulator of
      pulmonary fibrosis. IL-1R-associated kinase-M (IRAK-M), a MyD88-dependent
      inhibitor of TLR signaling, suppresses deleterious inflammation, but may
      paradoxically promote fibrogenesis. Mice deficient in IRAK-M (IRAK-M(-/-)) were
      protected against bleomycin-induced fibrosis and displayed diminished collagen
      deposition in association with reduced production of IL-13 compared with wild
      type (WT) control mice. Bone marrow chimera experiments indicated that IRAK-M
      expression by bone marrow-derived cells, rather than structural cells, promoted
      fibrosis. After bleomycin, WT macrophages displayed an alternatively activated
      phenotype, whereas IRAK-M(-/-) macrophages displayed higher expression of
      classically activated macrophage markers. Using an in vitro coculture system,
      macrophages isolated from in vivo bleomycin-challenged WT, but not IRAK-M(-/-),
      mice promoted increased collagen and alpha-smooth muscle actin expression from
      lung fibroblasts in an IL-13-dependent fashion. Finally, IRAK-M expression is
      upregulated in peripheral blood cells from idiopathic pulmonary fibrosis patients
      and correlated with markers of alternative macrophage activation. These data
      indicate expression of IRAK-M skews lung macrophages toward an alternatively
      activated profibrotic phenotype, which promotes collagen production, leading to
      the progression of experimental pulmonary fibrosis. 

PMID- 25595782
TI  - IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic
      dysfunction in a mouse model of lupus-associated atherosclerosis.
AB  - Premature atherosclerosis is a severe complication of lupus and other systemic
      autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5
      (IRF5) are associated with an increased risk of developing lupus, and IRF5
      deficiency in lupus mouse models ameliorates disease. However, whether IRF5
      deficiency also protects against atherosclerosis development in lupus is not
      known. In this study, we addressed this question using the gld.apoE(-/-) mouse
      model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly,
      despite the reduction in systemic immune activation, IRF5-deficient mice
      developed increased atherosclerosis and also exhibited metabolic dysregulation
      characterized by hyperlipidemia, increased adiposity, and insulin resistance.
      Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5
      deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10
      production downstream of TLR7 and TLR9 signaling in multiple immune cell types.
      Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents
      lupus development and contributes in part to the increased atherosclerosis.
      Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the
      increased atherosclerosis through the generation of hyperlipidemia and increased
      adiposity. Together, our results reveal a protective role for IRF5 in lupus
      associated atherosclerosis that is mediated through the effects of IRF5 in both
      immune and nonimmune cells. These findings have implications for the proposed
      targeting of IRF5 in the treatment of autoimmune disease as global IRF5
      inhibition may exacerbate cardiovascular disease in these patients. 

PMID- 25595783
TI  - Elevation of c-MYC disrupts HLA class II-mediated immune recognition of human B
      cell tumors.
AB  - Elevated levels of the transcription factor c-myc are strongly associated with
      various cancers, and in particular B cell lymphomas. Although many of c-MYC's
      functions have been elucidated, its effect on the presentation of Ag through the
      HLA class II pathway has not been reported previously. This is an issue of
      considerable importance, given the low immunogenicity of many c-MYC-positive
      tumors. We report in this paper that increased c-MYC expression has a negative
      effect on the ability of B cell lymphomas to functionally present Ags/peptides to
      CD4(+) T cells. This defect was associated with alterations in the expression of
      distinct cofactors as well as interactions of antigenic peptides with class II
      molecules required for the presentation of class II-peptide complexes and T cell
      engagement. Using early passage Burkitt's lymphoma (BL) tumors and transformed
      cells, we show that compared with B lymphoblasts, BL cells express decreased
      levels of the class II editor HLA-DM, lysosomal thiol-reductase GILT, and a 47
      kDa enolase-like protein. Functional Ag presentation was partially restored in BL
      cells treated with a c-MYC inhibitor, demonstrating the impact of this oncogene
      on Ag recognition. This restoration of HLA class II-mediated Ag presentation in
      early passage BL tumors/cells was linked to enhanced HLA-DM expression and a
      concurrent decrease in HLA-DO in BL cells. Taken together, these results reveal c
      MYC exerts suppressive effects at several critical checkpoints in Ag
      presentation, which contribute to the immunoevasive properties of BL tumors. 

PMID- 25595785
TI  - NFAT1 and JunB cooperatively regulate IL-31 gene expression in CD4+ T cells in
      health and disease.
AB  - IL-31 is a key mediator of itching in atopic dermatitis (AD) and is
      preferentially produced by activated CD4(+) T cells and Th2 cells. Although
      pathophysiological functions of IL-31 have been suggested in diverse immune
      disorders, the molecular events underlying IL-31 gene regulation are still
      unclear. In this study we identified the transcription start site and functional
      promoter involved in IL-31 gene regulation in mouse CD4(+) T cells. TCR
      stimulation-dependent IL-31 expression was found to be closely linked with in
      vivo binding of NFAT1 and JunB to the IL-31 promoter. Although NFAT1 alone
      enhanced IL-31 promoter activity, it was further enhanced in the presence of
      JunB. Conversely, knockdown of either NFAT1 or JunB resulted in reduced IL-31
      expression. NFAT1-deficient CD4(+) T cells showed a significant defect in IL-31
      expression compared with wild-type CD4(+) T cells. In agreement with these
      findings, mice subjected to atopic conditions showed much higher levels of IL-31,
      which were closely correlated with a significant increase in the number of
      infiltrated NFAT1(+)CD4(+) T cells into the AD ears. Amelioration of AD
      progression by cyclosporin A treatment was well correlated with downregulation of
      IL-31 expressions in CD4(+) T cells and total ear residual cells. In summary, our
      results suggest a functional cooperation between NFAT1 and JunB in mediating IL
      31 gene expression in CD4(+) T cells and indicate that interference with this
      interaction or their activity has the potential of reducing IL-31-mediated AD
      symptoms. 

PMID- 25595784
TI  - Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs
      their responsiveness to pathogen challenge.
AB  - Patients surviving the acute stages of sepsis develop compromised T cell immunity
      and increased susceptibility to infection. Little is known about the decreased
      CD4 T cell function after sepsis. We tracked the loss and recovery of endogenous
      Ag-specific CD4 T cell populations after cecal ligation and puncture-induced
      sepsis and analyzed the CD4 T cell response to heterologous infection during or
      after recovery. We observed that the sepsis-induced early loss of CD4 T cells was
      followed by thymic-independent numerical recovery in the total CD4 T cell
      compartment. Despite this numerical recovery, we detected alterations in the
      composition of naive CD4 T cell precursor pools, with sustained quantitative
      reductions in some populations. Mice that had experienced sepsis and were then
      challenged with epitope-bearing, heterologous pathogens demonstrated
      significantly reduced priming of recovery-impaired Ag-specific CD4 T cell
      responses, with regard to both magnitude of expansion and functional capacity on
      a per-cell basis, which also correlated with intrinsic changes in Vbeta clonotype
      heterogeneity. Our results demonstrate that the recovery of CD4 T cells from
      sepsis-induced lymphopenia is accompanied by alterations to the composition and
      function of the Ag-specific CD4 T cell repertoire. 

PMID- 25595787
TI  - Expansion of an atypical NK cell subset in mouse models of systemic lupus
      erythematosus.
AB  - Chronic inflammatory conditions, such as in autoimmune disease, can disturb
      immune cell homeostasis and induce the expansion of normally rare cell
      populations. In our analysis of various murine models of lupus, we detect
      increased frequency of an uncommon subset identified as
      NK1.1(+)CD11c(+)CD122(+)MHC class II(+). These cells share characteristics with
      the NK cell lineage and with cells previously described as IFN-producing killer
      dendritic cells: 1) they depend on IL-15 and express E4BP4; 2) they are cytotoxic
      and produce type I and type II IFN upon activation; and 3) they are efficient
      APCs both through MHC class II expression and in cross-presentation to CD8s.
      These atypical NK cells are responsive to TLR stimulation and thus are most
      abundant in mice with high copy number of the Tlr7 gene. They are highly
      proliferative as assessed by in vivo BrdU incorporation. In adoptive transfer
      experiments they persist in high numbers for months and maintain their surface
      marker profile, indicating that this population is developmentally stable. Gene
      expression analyses on both mRNA and microRNAs show a modified cell cycle program
      in which various miR-15/16 family members are upregulated, presumably as a
      consequence of the proliferative signal mediated by the increased level of growth
      factors, Ras and E2F activity. Alternatively, low expression of miR-150, miR-181,
      and miR-744 in these cells implies a reduction in their differentiation capacity.
      These results suggest that cells of the NK lineage that undergo TLR stimulation
      might turn on a proliferative program in detriment of their full differentiation
      into mature NK cells. 

PMID- 25595786
TI  - PTEN is a negative regulator of NK cell cytolytic function.
AB  - Human NK cells are characterized by their ability to initiate an immediate and
      direct cytolytic response to virally infected or malignantly transformed cells.
      Within human peripheral blood, the more mature CD56(dim) NK cell efficiently
      kills malignant targets at rest, whereas the less mature CD56(bright) NK cells
      cannot. In this study, we show that resting CD56(bright) NK cells express
      significantly more phosphatase and tensin homolog deleted on chromosome 10 (PTEN)
      protein when compared with CD56(dim) NK cells. Consistent with this, forced
      overexpression of PTEN in NK cells resulted in decreased cytolytic activity, and
      loss of PTEN in CD56(bright) NK cells resulted in elevated cytolytic activity.
      Comparable studies in mice showed PTEN overexpression did not alter NK cell
      development or NK cell-activating and inhibitory receptor expression yet, as in
      humans, did decrease expression of downstream NK activation targets MAPK and AKT
      during early cytolysis of tumor target cells. Confocal microscopy revealed that
      PTEN overexpression disrupts the NK cell's ability to organize immunological
      synapse components including decreases in actin accumulation, polarization of the
      microtubule organizing center, and the convergence of cytolytic granules. In
      summary, our data suggest that PTEN normally works to limit the NK cell's
      PI3K/AKT and MAPK pathway activation and the consequent mobilization of cytolytic
      mediators toward the target cell and suggest that PTEN is among the active
      regulatory components prior to human NK cells transitioning from the noncytolytic
      CD56(bright) NK cell to the cytolytic CD56(dim) NK cells. 

PMID- 25595789
TI  - Neurturin influences inflammatory responses and airway remodeling in different
      mouse asthma models.
AB  - Neurturin (NTN) was previously described for its neuronal activities, but
      recently, we have shown that this factor is also involved in asthma
      physiopathology. However, the underlying mechanisms of NTN are unclear. The aim
      of this study was to investigate NTN involvement in acute bronchial Th2
      responses, to analyze its interaction with airway structural cells, and to study
      its implication in remodeling during acute and chronic bronchial inflammation in
      C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild
      type and NTN(-/-) mice after sensitization with two different allergens, OVA and
      house dust mite. We showed that NTN(-/-) dendritic cells and T cells had a
      stronger tendency to activate the Th2 pathway in vitro than similar wild-type
      cells. Furthermore, NTN(-/-) mice had significantly increased markers of airway
      remodeling like collagen deposition. NTN(-/-) lung tissues showed higher levels
      of neutrophils, cytokine-induced neutrophil chemoattractant, matrix
      metalloproteinase 9, TNF-alpha, and IL-6. Finally, NTN had the capacity to
      decrease IL-6 and TNF-alpha production by immune and epithelial cells, showing a
      direct anti-inflammatory activity on these cells. Our findings support the
      hypothesis that NTN could modulate the allergic inflammation in different mouse
      asthma models. 

PMID- 25595788
TI  - Deficiency of antigen-specific B cells results in decreased Trypanosoma cruzi
      systemic but not mucosal immunity due to CD8 T cell exhaustion.
AB  - Vaccines against mucosally invasive, intracellular pathogens must induce a myriad
      of immune responses to provide optimal mucosal and systemic protection, including
      CD4(+) T cells, CD8(+) T cells, and Ab-producing B cells. In general, CD4(+) T
      cells are known to provide important helper functions for both CD8(+) T cell and
      B cell responses. However, the relative importance of CD4(+) T cells, CD8(+) T
      cells, and B cells for mucosal protection is less clearly defined. We have
      studied these questions in detail using the murine model of Trypanosoma cruzi
      infection. Despite our initial hypothesis that mucosal Abs would be important, we
      show that B cells are critical for systemic, but not mucosal, T. cruzi protective
      immunity. B cell-deficient mice developed normal levels of CD8(+) effector T cell
      responses early after mucosal T. cruzi infection and T. cruzi trans-sialidase
      vaccination. However, after highly virulent systemic challenge, T. cruzi immune
      mice lacking T. cruzi-specific B cells failed to control parasitemia or prevent
      death. Mechanistically, T. cruzi-specific CD8(+) T cells generated in the absence
      of B cells expressed increased PD-1 and Lag-3 and became functionally exhausted
      after high-level T. cruzi systemic challenge. T. cruzi immune serum prevented
      CD8(+) T cell functional exhaustion and reduced mortality in mice lacking B
      cells. Overall, these results demonstrate that T. cruzi-specific B cells are
      necessary during systemic, but not mucosal, parasite challenge. 

PMID- 25595790
TI  - Loss of mouse P2Y4 nucleotide receptor protects against myocardial infarction
      through endothelin-1 downregulation.
AB  - Nucleotides are released in the heart under pathological conditions, but little
      is known about their contribution to cardiac inflammation. The present study
      defines the P2Y4 nucleotide receptor, expressed on cardiac microvascular
      endothelial cells and involved in postnatal heart development, as an important
      regulator of the inflammatory response to cardiac ischemia. P2Y4-null mice
      displayed smaller infarcts in the left descending artery ligation model, as well
      as reduced neutrophil infiltration and fibrosis. Gene profiling identified inter
      alia endothelin-1 (ET-1) as one of the target genes of P2Y4 in ischemic heart.
      The reduced level of ET-1 was correlated with reduction of microvascular
      hyperpermeability, neutrophil infiltration, and endothelial adhesion molecule
      expression, and it could be explained by the decreased number of endothelial
      cells in P2Y4-null mice. Expression analysis of metalloproteinases and their
      tissue inhibitors in ischemic heart revealed reduced expression of matrix
      metalloproteinase (MMP)-9, reported to be potentially regulated by ET-1, and MMP
      8, considered as neutrophil collagenase, as well as reduction of tissue inhibitor
      of MMP-1 and tissue inhibitor of MMP-4 in P2Y4-null mice. Reduction of cardiac
      permeability and neutrophil infiltration was also observed in P2Y4-null mice in
      LPS-induced inflammation model. Protection against infarction resulting from loss
      of P2Y4 brings new therapeutic perspectives for cardiac ischemia and remodeling. 

PMID- 25595791
TI  - Natural IgM prevents autoimmunity by enforcing B cell central tolerance
      induction.
AB  - It is unclear why selective deficiency in secreted (s)IgM causes Ab-mediated
      autoimmunity. We demonstrate that sIgM is required for normal B cell development
      and selection. The CD5(+) B cells that were previously shown to accumulate in
      body cavities of sIgM(-/-) mice are not B-1a cells, but CD19(int), CD43(-), short
      lived, BCR signaling-unresponsive anergic B-2 cells. Body cavity B-1 cells were
      >10-fold reduced, including VH11(+) and phosphotidylcholine-specific B-1a cells,
      whereas splenic B-1 cells were unaffected and marginal zone B cells increased.
      Follicular B cells had higher turnover rates, survived poorly after adoptive
      transfer, and were unresponsiveness to BCR stimulation in vitro. sIgM bound to B
      cell precursors and provided a positive signal to overcome a block at the pro/pre
      B stage and during IgVH repertoire selection. Polyclonal IgM rescued B cell
      development and returned autoantibody levels to near normal. Thus, natural IgM
      deficiency causes primary autoimmune disease by altering B cell development,
      selection, and central tolerance induction. 

PMID- 25595794
TI  - An unusual case of gastritis and duodenitis after yttrium 90-microsphere
      selective internal radiation.

PMID- 25595792
TI  - Memory T cells specific for murine cytomegalovirus re-emerge after multiple
      challenges and recapitulate immunity in various adoptive transfer scenarios.
AB  - Reconstitution of CMV-specific immunity after transplant remains a primary
      clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV
      specific T cells can be an effective therapeutic approach. Because of viral
      persistence, most CMV-specific CD8(+) T cells become terminally differentiated
      effector phenotype CD8(+) T cells (TEFF). A minor subset retains a memory-like
      phenotype (memory phenotype CD8(+) T cells [TM]), but it is unknown whether these
      cells retain memory function or persist over time. Interestingly, recent studies
      suggest that CMV-specific CD8(+) T cells with different phenotypes have different
      abilities to reconstitute sustained immunity after transfer. The immunology of
      human CMV infections is reflected in the murine CMV (MCMV) model. We found that
      human CMV- and MCMV-specific T cells displayed shared genetic programs,
      validating the MCMV model for studies of CMV-specific T cells in vivo. The MCMV
      specific TM population was stable over time and retained a proliferative capacity
      that was vastly superior to TEFF. Strikingly, after transfer, TM established
      sustained and diverse T cell populations even after multiple challenges. Although
      both TEFF and TM could protect Rag(-/-) mice, only TM persisted after transfer
      into immune replete, latently infected recipients and responded if recipient
      immunity was lost. Interestingly, transferred TM did not expand until recipient
      immunity was lost, supporting that competition limits the Ag stimulation of TM.
      Ultimately, these data show that CMV-specific TM retain memory function during
      MCMV infection and can re-establish CMV immunity when necessary. Thus, TM may be
      a critical component for consistent, long-term adoptive immunotherapy success. 

PMID- 25595793
TI  - Evasion of innate cytosolic DNA sensing by a gammaherpesvirus facilitates
      establishment of latent infection.
AB  - Herpesviruses are DNA viruses harboring the capacity to establish lifelong latent
      recurrent infections. There is limited knowledge about viruses targeting the
      innate DNA-sensing pathway, as well as how the innate system impacts on the
      latent reservoir of herpesvirus infections. In this article, we report that
      murine gammaherpesvirus 68 (MHV68), in contrast to alpha- and beta-herpesviruses,
      induces very limited innate immune responses through DNA-stimulated pathways,
      which correspondingly played only a minor role in the control of MHV68 infections
      in vivo. Similarly, Kaposi's sarcoma-associated herpesvirus also did not
      stimulate immune signaling through the DNA-sensing pathways. Interestingly, an
      MHV68 mutant lacking deubiquitinase (DUB) activity, embedded within the large
      tegument protein open reading frame (ORF)64, gained the capacity to stimulate the
      DNA-activated stimulator of IFN genes (STING) pathway. We found that ORF64
      targeted a step in the DNA-activated pathways upstream of the bifurcation into
      the STING and absent in melanoma 2 pathways, and lack of the ORF64 DUB was
      associated with impaired delivery of viral DNA to the nucleus, which, instead,
      localized to the cytoplasm. Correspondingly, the ORF64 DUB active site mutant
      virus exhibited impaired ability to establish latent infection in wild-type, but
      not STING-deficient, mice. Thus, gammaherpesviruses evade immune activation by
      the cytosolic DNA-sensing pathway, which, in the MHV68 model, facilitates
      establishment of infections. 

PMID- 25595795
TI  - A Rare Case of Diffuse Polyps of Small Intestine With Abdominal Mass.

PMID- 25595796
TI  - Weight loss, saline loading, and the natriuretic peptide system.
AB  - BACKGROUND: In epidemiologic studies, obesity has been associated with reduced
      natriuretic peptide (NP) concentrations. Reduced NP production could impair the
      ability of obese individuals to respond to salt loads, increasing the risk of
      hypertension and other disorders. We hypothesized that weight loss enhances NP
      production before and after salt loading. METHODS AND RESULTS: We enrolled 15
      obese individuals (mean BMI 45+/-5.4 kg/m(2)) undergoing gastric bypass surgery.
      Before and 6 months after surgery, subjects were admitted to the clinical
      research center and administered a large-volume intravenous saline challenge.
      Echocardiography and serial blood sampling were performed. From the pre-operative
      visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the
      6-month visit, N-terminal pro-atrial NP (Nt-proANP) levels were 40% higher
      before, during, and after the saline infusion, compared with levels measured at
      the same time points during the pre-operative visit (P<0.001). The rise in Nt-pro
      ANP induced by the saline infusion (~50%) was similar both before and after
      surgery (saline, P<0.001; interaction, P=0.2). Similar results were obtained for
      BNP and Nt-proBNP; resting concentrations increased by 50% and 31%, respectively,
      after gastric bypass surgery. The increase in NP concentrations after surgery was
      accompanied by significant decreases in mean arterial pressure (P=0.004) and
      heart rate (P<0.001), and an increase in mitral annular diastolic velocity
      (P=0.02). CONCLUSION: In obese individuals, weight loss is associated with a
      substantial increase in the "setpoint" of circulating NP concentrations. Higher
      NP concentrations could contribute to an enhanced ability to handle salt loads
      after weight loss.

PMID- 25595797
TI  - Home treatments alone or mixed with modern treatments for malaria in Finkolo AC,
      South Mali: reported use, outcomes and changes over 10 years.
AB  - BACKGROUND: In 2003, a study in Mali showed that 87% of episodes of uncomplicated
      malaria were first treated at home. We investigated whether treatment-seeking
      patterns in Mali had changed 10 years later. METHODS: In 2013, we repeated the
      retrospective treatment-outcome study on 400 children with presumed malaria in
      the same area. RESULTS: Most children with reported uncomplicated malaria were
      still first treated at home (76% [196/258] in 2013 vs 85% in 2003; p=0.006),
      rather than in modern health centres (20% [52/258] in 2013 vs 12% in 2003;
      p=0.01). Overall, 58% of children with uncomplicated malaria were treated with
      herbal medicine alone, a significant increase from 24% 10 years earlier
      (p<0.001). This was associated with an increase in use of Argemone mexicana
      decoction from 8% to 26% (p<0.001), with a reported cure or improvement in 100%
      of cases among those aged >5 years. For severe malaria, first treatment was
      sought less often from a traditional healer compared with 10 years earlier (4% vs
      32%; p<0.001) and more often from a modern health centre (29% vs 17%; p=0.04).
      CONCLUSIONS: Two trends that emerged are that there is a greater use of modern
      health facilities for treatment of severe malaria, and a greater use of
      traditional medicine alone for treatment of uncomplicated malaria.

PMID- 25595800
TI  - Alphavirus entry into host cells.
AB  - Viruses have evolved to exploit the vast complexity of cellular processes for
      their success within the host cell. The entry mechanisms of enveloped viruses
      (viruses with a surrounding outer lipid bilayer membrane) are usually classified
      as being either endocytotic or fusogenic. Different mechanisms have been proposed
      for Alphavirus entry and genome delivery. Indirect observations led to a general
      belief that enveloped viruses can infect cells either by protein-assisted fusion
      with the plasma membrane in a pH-independent manner or by endocytosis and fusion
      with the endocytic vacuole in a low-pH environment. The mechanism of Alphavirus
      penetration has been recently revisited using direct observation of the processes
      by electron microscopy under conditions of different temperatures and time
      progression. Under conditions nonpermissive for endocytosis or any vesicular
      transport, events occur which allow the entry of the virus genome into the cells.
      When drug inhibitors of cellular functions are used to prevent entry, only
      ionophores are found to significantly inhibit RNA delivery. Arboviruses are
      agents of significant human and animal disease; therefore, strategies to control
      infections are needed and include development of compounds which will block
      critical steps in the early infection events. It appears that current evidence
      points to an entry mechanism, in which alphaviruses infect cells by direct
      penetration of cell plasma membranes through a pore structure formed by virus
      and, possibly, host proteins. 

PMID- 25595801
TI  - The mechanism of HCV entry into host cells.
AB  - Hepatitis C virus (HCV) is an enveloped, positive strand RNA virus classified
      within the Flaviviridae family and is a major cause of liver disease worldwide.
      HCV life cycle and propagation are tightly linked to several aspects of lipid
      metabolism. HCV propagation depends on and also shapes several aspects of lipid
      metabolism such as cholesterol uptake and efflux through different lipoprotein
      receptors during its entry into cells, lipid metabolism modulating HCV genome
      replication, lipid droplets acting as a platform for recruitment of viral
      components, and very low density lipoprotein assembly pathway resulting in
      incorporation of neutral lipids and apolipoproteins into viral particles. During
      the first steps of infection, HCV enters hepatocytes through a multistep and slow
      process. The initial capture of HCV particles by glycosaminoglycans and/or
      lipoprotein receptors is followed by coordinated interactions with the scavenger
      receptor class B type I, a major receptor of high-density lipoprotein, the CD81
      tetraspanin, and the tight junction proteins Claudin-1 and Occludin. This tight
      concert of receptor interactions ultimately leads to uptake and cellular
      internalization of HCV through a process of clathrin-dependent endocytosis. Over
      the years, the identification of the HCV entry receptors and cofactors has led to
      a better understanding of HCV entry and of the narrow tropism of HCV for the
      liver. Yet, the role of the two HCV envelope glycoproteins, E1 and E2, remains
      ill-defined, particularly concerning their involvement in the membrane fusion
      process. Here, we review the current knowledge and advances addressing the
      mechanism of HCV cell entry within hepatocytes and we highlight the challenges
      that remain to be addressed. 

PMID- 25595802
TI  - The evolution of HIV-1 interactions with coreceptors and mannose C-type lectin
      receptors.
AB  - The phenotype of human immunodeficiency virus type 1 (HIV-1) commonly evolves
      between and within infected individuals, at virus transmission, and during
      disease progression. This evolution includes altered interactions between the
      virus and its coreceptors, i.e., chemokine receptors, as well as mannose C-type
      lectin receptors (CLRs). Transmitted/founder viruses are predominantly restricted
      to CCR5, whereas the subsequent intrapatient evolution of HIV-1 coreceptor use
      during progressive disease can be subdivided into two distinct pathways.
      Accordingly, the CCR5-restricted virus population is either gradually replaced by
      virus variants able to use CXCR4 or evolves toward an altered, more flexible use
      of CCR5. Despite a strong dependency on these coreceptors for host cell entry,
      HIV-1 also interacts with other cell surface molecules during target cell
      attachment, including the CLRs. The virus interaction with the CLRs may result
      either in the efficient transfer of virus to CD4(+) T cells or in the degradation
      of the virus in endosomal compartments. The determinants of the diverse outcomes
      depend on which CLR is engaged and also on the glycan makeup of the envelope
      glycoproteins, which may evolve with the strength of the immune pressure during
      the disease course. With the current clinical introduction of CCR5 antagonists
      and the development of additional entry inhibitors, knowledge on the evolution
      and baseline characteristics of HIV-1 interactions with coreceptor and CLR
      interactions may play important roles for individualized and optimized treatment
      strategies. This review summarizes our current understanding of the evolution of
      HIV-1 interactions with these receptors. 

PMID- 25595798
TI  - Transport through recycling endosomes requires EHD1 recruitment by a
      phosphatidylserine translocase.
AB  - P4-ATPases translocate aminophospholipids, such as phosphatidylserine (PS), to
      the cytosolic leaflet of membranes. PS is highly enriched in recycling endosomes
      (REs) and is essential for endosomal membrane traffic. Here, we show that PS
      flipping by an RE-localized P4-ATPase is required for the recruitment of the
      membrane fission protein EHD1. Depletion of ATP8A1 impaired the asymmetric
      transbilayer distribution of PS in REs, dissociated EHD1 from REs, and generated
      aberrant endosomal tubules that appear resistant to fission. EHD1 did not show
      membrane localization in cells defective in PS synthesis. ATP8A2, a tissue
      specific ATP8A1 paralogue, is associated with a neurodegenerative disease
      (CAMRQ). ATP8A2, but not the disease-causative ATP8A2 mutant, rescued the
      endosomal defects in ATP8A1-depleted cells. Primary neurons from Atp8a2-/- mice
      showed a reduced level of transferrin receptors at the cell surface compared to
      Atp8a2+/+ mice. These findings demonstrate the role of P4-ATPase in membrane
      fission and give insight into the molecular basis of CAMRQ.

PMID- 25595804
TI  - TRIM21-dependent intracellular antibody neutralization of virus infection.
AB  - The ability of antibodies to prevent viral infection has long been recognized. In
      vitro neutralization assays, which take place in the absence of professional
      immune effector mechanisms, have demonstrated that the process of neutralization
      can occur by a variety of molecular mechanisms. Most known mechanisms involve the
      blocking of an event essential for infection, for instance, the steric inhibition
      of attachment to entry receptors. As such, neutralization is often thought of as
      a passive process that can occur without the need for host effector machinery. In
      contrast to this view, it has recently been demonstrated that neutralization can
      depend on the widely expressed cytosolic Fc binding protein TRIM21. This unique
      and novel Ig receptor directs the ubiquitin and proteasome-dependent degradation
      of intracellular antibody-bound viral particles and prevents infection. It has
      been further demonstrated that detection of cytosolic antibody by TRIM21
      activates inflammatory signaling pathways and promotes the production of
      cytokines and chemokines. Studies in a TRIM21-null mouse demonstrate the
      importance of these activities: homozygous knockouts suffer fatal viral infection
      where wild-type mice survive. Though there is much to be learned about the role
      of TRIM21 in immunity, it is clear that there is a hitherto unappreciated role
      for antibodies in the intracellular environment. 

PMID- 25595805
TI  - Picornavirus--host interactions to construct viral secretory membranes.
AB  - Picornaviruses are positive-stranded RNA viruses of significant disease burden
      and ubiquitous global reach. Microscopic examination of picornavirus-infected
      cells has long revealed a drastic reordering of intracellular membranes. Through
      a confluence of candidate-based approaches and genomic and proteomic screens, the
      past decade has seen great leaps in understanding how picornaviruses usurp
      intracellular membranes for their own replication. The growing cast of assembled
      characters allows for a rich plot in the upcoming years. With their widespread
      genomic divergence, the number of potential mechanisms for RNA virus
      vesicogenesis for driving membrane formation and lipid synthesis required for
      viral replication is broad, but the overall story arch remains surprisingly
      recognizable. This chapter reviews the major discoveries associating picornavirus
      pathogenic interactions with the secretory system and highlights important
      questions and opportunities for future study. 

PMID- 25595799
TI  - Unity in diversity: shared mechanism of entry among paramyxoviruses.
AB  - The Paramyxoviridae family includes many viruses that are pathogenic in humans,
      including parainfluenza viruses, measles virus, respiratory syncytial virus, and
      the emerging zoonotic Henipaviruses. No effective treatments are currently
      available for these viruses, and there is a need for efficient antiviral
      therapies. Paramyxoviruses enter the target cell by binding to a cell surface
      receptor and then fusing the viral envelope with the target cell membrane,
      allowing the release of the viral genome into the cytoplasm. Blockage of these
      crucial steps prevents infection and disease. Binding and fusion are driven by
      two virus-encoded glycoproteins, the receptor-binding protein and the fusion
      protein, that together form the viral "fusion machinery." The development of
      efficient antiviral drugs requires a deeper understanding of the mechanism of
      action of the Paramyxoviridae fusion machinery, which is still controversial.
      Here, we review recent structural and functional data on these proteins and the
      current understanding of the mechanism of the paramyxovirus cell entry process. 

PMID- 25595806
TI  - Retroviral factors promoting infectivity.
AB  - The ability of a virus particle to establish an infectious event is a fundamental
      property required for viral propagation and survival. Retrovirus invasion of
      target cells is a multistep process that begins with entry into the cytoplasm and
      culminates with the integration of the proviral genome into the host DNA. Along
      this journey, many obstacles await the retrovirus particle and undermine its
      infectivity. Host-cell barriers to retrovirus infection can either be basic
      structural components of the eukaryotic cell or specific antiretroviral
      activities developed by the cell to prevent the retroviral invasion. Resulting
      from a long host-parasite coevolution, retroviruses have developed auxiliary
      factors that promote infectivity by conferring the virion the ability to overcome
      several cellular obstacles, which interfere with the infection process. Here, we
      provide an overview of different retroviral auxiliary factors that promote virion
      infectivity, comparing their mechanism of action and highlighting common
      mechanistic strategies. Special attention is given to infectivity factors that
      remain enigmatic in the biology of retroviruses. 

PMID- 25595803
TI  - A game of numbers: the stoichiometry of antibody-mediated neutralization of
      flavivirus infection.
AB  - The humoral response contributes to the protection against viral pathogens.
      Although antibodies have the potential to inhibit viral infections via several
      mechanisms, an ability to neutralize viruses directly may be particularly
      important. Neutralizing antibody titers are commonly used as predictors of
      protection from infection, especially in the context of vaccine responses and
      immunity. Despite the simplicity of the concept, how antibody binding results in
      virus inactivation is incompletely understood despite decades of research.
      Flaviviruses have been an attractive system in which to seek a structural and
      quantitative understanding of how antibody interactions with virions modulate
      infection because of the contribution of antibodies to both protection and
      pathogenesis. This review will present a stoichiometric model of antibody
      mediated neutralization of flaviviruses and discuss how these concepts can inform
      the development of vaccines and antibody-based therapeutics. 

PMID- 25595807
TI  - The cytoplasmic tail of retroviral envelope glycoproteins.
AB  - Retroviruses comprise a large, diverse group that infects a broad range of host
      organisms. Pathogenicity varies widely; the human immunodeficiency virus is the
      causative agent of acquired immunodeficiency syndrome, one of the world's leading
      infectious causes of death, while many nonhuman retroviruses cause cancer in the
      host. Retroviruses have been studied intensively, and great strides have been
      made in understanding aspects of retroviral biology. While the principal
      functions of the viral structural proteins are well understood, there remain many
      incompletely characterized domains. One of these is the cytoplasmic tail (CT) of
      the envelope glycoprotein. Several functions of the CT are highly conserved,
      whereas other properties are unique to a specific retrovirus. For example, the
      lentiviruses encode envelope glycoproteins with particularly large cytoplasmic
      domains. The functions of the long lentiviral envelope CT are still being
      deciphered. The reported functions of retroviral envelope CTs are discussed in
      this chapter. 

PMID- 25595809
TI  - The role of chance in primate lentiviral infectivity: from protomer to host
      organism.
AB  - Infection is best described as a stochastic process. Whether a host becomes
      infected upon exposure has a strong random element. The same applies to cells
      exposed to virions. In this review, we show how the mathematical formalism for
      stochastic processes has been used to describe and understand the infection by
      the Human and Simian Immunodeficiency Virus on different levels. We survey
      quantitative studies on the establishment of infection in the host (the
      organismal level) and on the infection of target cells (the cellular and
      molecular level). We then discuss how a synthesis of the approaches across these
      levels could give rise to a predictive framework for assessing the efficacy of
      microbicides and vaccines. 

PMID- 25595810
TI  - Virus-encoded 7 transmembrane receptors.
AB  - Herpesviruses are an ancient group which have exploited gene capture of multiple
      cellular modulators of the immune response. Viral homologues of 7 transmembrane
      receptors (v7TMRs) are a consistent feature of beta- and gammaherpesviruses; the
      majority of the v7TMRs are homologous to cellular chemokine receptors (CKRs).
      Conserved families of v7TMRs distinguish between beta- versus gammaherpesviruses;
      furthermore, significant divisions within these subfamilies, such as between
      genera of the gammaherpesviruses or between the primate and rodent
      cytomegaloviruses, coincide with specific v7TMR gene families. Divergence of
      functional properties between the viral 7TMR and their cellular counterparts is
      likely, therefore, to reflect adaptation supporting various aspects of the viral
      lifecycle with concomitant effects upon viral pathogenesis. Consistent with their
      long evolutionary history, the v7TMRs have acquired a range of distinctive
      characteristics. This chapter reviews key features of the v7TMRs which are likely
      to impact upon their functional roles: trafficking properties, ligand
      specificity, and signaling capacity. Rapid, constitutive endocytosis, reminiscent
      of cellular "scavenger" receptors, may provide a mechanism for immune evasion, or
      alternatively relate to virion assembly, including incorporation of v7TMRs within
      the virion envelope. Some v7TMRs display relatively broad chemokine-binding
      specificity, whereas others remain "orphan" and may be completely independent of
      ligand activation. Indeed, many of the v7TMRs have been shown to signal
      constitutively, associated in some cases with notable divergence of highly
      conserved regulatory elements such as the "DRY" motif of TMIII. The availability
      of rodent models for v7TMR functional studies has provided evidence for important
      biological roles, including cellular transformation, tissue tropism, and viral
      persistence. Recent studies addressing signaling pathways critical to these
      phenotypes will be discussed, with reference to both beta- and
      gammaherpesviruses. 

PMID- 25595811
TI  - EBV, the human host, and the 7TM receptors: defense or offense?
AB  - Being present in around 90% of the worldwide population, Epstein-Barr virus (EBV)
      is an exceptionally prevalent virus. This highly successful virus establishes a
      latent infection in resting memory B cells and is maintained in a balance between
      viral homeostasis on one side and antiviral defense of the immune system on the
      other side. The life cycle of EBV is dependent on many viral proteins, but EBV
      also regulates a number of endogenous proteins. 7TM receptors and ligands of
      viral and host origin are examples of such proteins. 7TM receptors are highly
      druggable and they are among the most popular class of investigational drug
      targets. The 7TM receptor encoded by EBV-BILF1, is known to downregulate cell
      surface MHC class I expression as part of the immune evasion strategy of EBV.
      However, the functional impact of the relationship between EBV and the regulated
      endogenous 7TM receptors and ligands is still unclear. This is for instance the
      case for the most upregulated 7TM receptor EBI2 (EBV-induced gene 2 or GPR183).
      Whereas some regulated genes have been suggested to be involved in the EBV life
      cycle, others could also be important for the antiviral immune defense. As many
      of these 7TM receptors and ligands have been shown to be modulated in EBV
      associated diseases, targeting these could provide an efficient and specific way
      to inhibit EBV-associated disease progression. Here, we will review current
      knowledge on EBV infection, the immune defense against EBV and 7TM receptors and
      ligands being either encoded or manipulated by EBV. 

PMID- 25595812
TI  - The molecular basis of viral infection. Preface.

PMID- 25595808
TI  - Molecular determinants of the ratio of inert to infectious virus particles.
AB  - The ratio of virus particles to infectious units is a classic measurement in
      virology and ranges widely from several million to below 10 for different
      viruses. Much evidence suggests a distinction be made between infectious and
      infecting particles or virions: out of many potentially infectious virions, few
      infect under regular experimental conditions, largely because of diffusion
      barriers. Still, some virions are inert from the start; others become defective
      through decay. And with increasing cell- and molecular-biological knowledge of
      each step in the replicative cycle for different viruses, it emerges that many
      processes entail considerable losses of potential viral infectivity. Furthermore,
      all-or-nothing assumptions about virion infectivity are flawed and should be
      replaced by descriptions that allow for spectra of infectious propensities. A
      more realistic understanding of the infectivity of individual virions has both
      practical and theoretical implications for virus neutralization, vaccine
      research, antiviral therapy, and the use of viral vectors. 

PMID- 25595813
TI  - Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB
      H: First-in-Human Study.
AB  - PURPOSE: [(18)F]UCB-H is a novel radiotracer with a high affinity for synaptic
      vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is
      the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a
      distinct but still poorly understood mechanism of action. The objective of this
      study was to determine the biodistribution and radiation dosimetry of [(18)F]UCB
      H in a human clinical trial and to establish injection limits according to
      biomedical research guidelines. Additionally, the clinical radiation dosimetry
      results were compared to estimations in previously published preclinical data.
      PROCEDURES: Dynamic whole body positron emission tomography/X-ray computed
      tomography (PET/CT) imaging was performed over approximately 110 min on five
      healthy male volunteers after injection of 144.5 +/- 7.1 MBq (range, 139.1-156.5
      MBq) of [(18)F]UCB-H. Major organs were delineated on CT images, and time
      activity curves were obtained from co-registered dynamic PET emission scans. The
      bladder could only be delineated on PET images. Time-integrated activity
      coefficients were calculated as area under the curve using trapezoidal numerical
      integration. Urinary excretion data based on PET activities including voiding was
      also simulated using the dynamic bladder module of OLINDA/EXM. The radiation
      dosimetry was calculated using OLINDA/EXM. RESULTS: The effective dose to the
      OLINDA/EXM 70-kg standard male was 1.54 * 10(-2) +/- 6.84 * 10(-4) millisieverts
      (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving
      the highest absorbed dose. The brain, the tracer's main organ of interest,
      received an absorbed dose of 1.89 * 10(-2) +/- 2.32 * 10(-3) mGy/MBq.
      CONCLUSIONS: This first human dosimetry study of [(18)F]UCB-H indicated that the
      tracer shows similar radiation burdens to widely used common clinical tracers.
      Single injections of at maximum 672 MBq for US practice and 649 MBq for European
      practice keep radiation exposure below recommended limits. Recently published
      preclinical dosimetry data extrapolated from mice provided satisfactory
      prediction of total body and effective dose but showed significant differences in
      organ absorbed doses compared to human data.

PMID- 25595814
TI  - Development and Evaluation of Transgenic Nude Mice Expressing Ubiquitous Green
      Fluorescent Protein.
AB  - PURPOSE: Researchers had developed and characterized transgenic green/red
      fluorescent protein (GFP/RFP) nude mouse with ubiquitous RFP or GFP expression,
      but none has evaluated the level of immune cells and expression levels of GFP in
      this model. PROCEDURE: The nude GFP mice were evaluated by imaging, hematological
      indices, and flow cytometry to compare the proportion of immune T cells.
      Quantitative real-time PCR (qRT-PCR) was done for evaluating the relative
      expression of GFP transcripts in few organs of the nude GFP mice. RESULTS: The
      hematological and immune cells of nude GFP were within the range of nude mice.
      However, the gene expression levels were relatively less in various tissues
      compared with B6 GFP mice. CONCLUSIONS: These findings suggest that nude GFP is
      an ideal model resembling normal nude mice; however, GFP expression in various
      tissues by fluorescence should be considered, as the expression of GFP differs in
      various organs.

PMID- 25595815
TI  - Interleukin-1beta and interleukin-6 gene polymorphisms are associated with
      manifestations of sickle cell anemia.
AB  - Sickle cell anemia (SCA), a disorder characterized by both acute and chronic
      inflammation, exhibits substantial phenotypic variability. Interleukin-1 beta (IL
      1beta) and IL-6 are important in acute and chronic diseases, and their single
      nucleotide polymorphisms (SNPs) have been considered as predictors of prognosis
      in several inflammatory conditions. This study aims at exploring possible
      association of IL-1beta and IL-6 SNPs as potential genetic modifiers and or
      predictors of SCA clinical and laboratory phenotypes. This cross-sectional study
      involved 107 SCA patients and 110 age, sex and ethnicity-matched healthy
      individuals. The SNPs were identified by PCR-RFLP for IL-1beta (-511C>T and
      +3954C>T) and IL-6 (-597G>A and -174G>C) genes. Associations between these SNPs
      and the clinical and laboratory profiles of patients with SCA were then
      determined. Allelic and genotypic frequencies of IL-1beta and IL-6 SNPs between
      patients with SCA and controls were similar and followed HWE. IL-1beta +3954C>T
      SNP was associated with increased risk of osteonecrosis, elevated pulmonary
      arterial pressure and lower absolute reticulocyte count, while IL-6 -597G>A was
      associated with higher likelihood of retinopathy and leg ulcer. These data
      indicate that IL-1beta and IL-6 gene SNPs are associated with SCA complications
      among Brazilian patients and may act as genetic predictors of SCA clinical
      heterogeneity.

PMID- 25595816
TI  - Prevalence of Toxoplasma gondii antibodies in domestic donkeys (Equus asinus) in
      Durango, Mexico slaughtered for human consumption.
AB  - BACKGROUND: Nothing is known about Toxoplasma gondii prevalence in donkeys in
      Mexico. Meat from donkey is consumed by humans in Mexico and also exported to
      other countries. We sought to determine the presence of antibodies against T.
      gondii in 239 domestic donkeys (Equus asinus) for slaughter in Durango, Mexico
      using the modified agglutination test (MAT). Donkeys were sampled in four
      premises (trade centers) where donkeys were gather for shipment to abattoirs in
      other Mexican states. RESULTS: Antibodies to T. gondii were found in 26 (10.9%)
      of 239 donkeys, with MAT titers of 1:25 in 7, 1:50 in 11, 1:100 in 6, and 1:200
      in 2. Seropositive donkeys were found in three (75%) of the four gathering
      premises studied. Seroprevalence in donkeys varied from 0% to 23.1% among
      gathering premises. The seroprevalence of T. gondii infection was comparable
      among donkeys regardless their age, sex or health status. Seropositivity to T.
      gondii was found in donkeys between 1 to 12 years old. Multivariate analysis
      showed that seropositivity to T. gondii was associated with the gathering
      premises (OR = 1.58; 95% CI: 1.11-2.24; P = 0.009). CONCLUSIONS: This is the
      first report of T. gondii infection in donkeys in Mexico. Results indicate that
      consumption of undercooked or raw meat from T. gondii-infected donkeys is
      potentially a source of T. gondii infection for humans.

PMID- 25595817
TI  - [Imaging characteristics of renal involvement in systemic IgG4 disease: about a
      case].

PMID- 25595818
TI  - [Psychotropic drugs during pregnancy and lactation: development practice].
AB  - INTRODUCTION: Pregnancy and the postpartum periods are particular for the
      mother's use of drugs. Therapeutic prescription must take into account the
      potential risk of fetal malformation, newborn's withdrawal syndrome, feeding type
      and potential risk of untreated maternal mental illness. Recommendations for good
      practice are constantly remodeling and their conclusions are sometimes
      contradictory. METHOD: The aim of this work is to develop an updated review, easy
      to use for any professional involved in the monitoring or prescription of a
      psychotropic medication (antidepressants, anxiolytics-hypnotics, neuroleptics,
      mood stabilizers and substitution treatment of opioid dependance) for pregnant or
      nursing women. RESULTS: These updates in tabular form are also based on our
      clinical experience as a team specializing in perinatal medicine.

PMID- 25595819
TI  - [Uveal metastasis of thyroid carcinomas. About 3 cases].
AB  - OBJECTIVE: To study the characteristics of ocular metastases of thyroid
      carcinomas through three observations of patients. RESULTS: Three patients aged
      respectively 41, 55 and 66 years were followed for thyroid carcinoma. All
      patients were treated by surgery followed by IRA therapy. They developed ocular
      metastases after a mean period of 10 years after thyroidectomy. They presented in
      addition multiple secondary sites such as bone, lungs and cerebrum. The uveal
      lesion was unilateral and localized at the choroid or iris. The predominant
      symptomatology was decreased visual acuity. The diagnosis was based on
      ophthalmoscopic examination and post-IRA therapy scan and was confirmed by
      anatomopathological study. Treatment options were respectively IRA therapy,
      sectoral iridectomy and enucleation. Evolution was fatal in 2 cases and towards
      aggravation for one case. CONCLUSION: Uveal metastases of thyroid cancer are
      associated with a pejorative prognosis. Ophthalmologic follow-up is necessary
      when patient presents warning sign mainly with metastatic follicular carcinoma.
      Conversely, thyroid carcinoma should be considered in the differential diagnosis
      of a uveal mass of unknown origin.

PMID- 25595820
TI  - [Stenting vs. surgery for symptomatic carotid stenosis].
AB  - Stenting is associated with a higher periprocedural risk of stroke compared to
      surgery. This higher stroke risk mainly concerns patients older than 70 years,
      whereas risk seems to be similar in patients younger than 70 years. After the
      procedural period, both surgery and stenting seem to be as effective to prevent
      stroke. Surgery remains the first choice intervention in patients with severe
      symptomatic carotid stenosis. It is reasonable to consider stenting in patients
      with contraindications to surgery due to technical or anatomical aspects, or in
      patients at high risk of complications because of comorbidities, after a
      multidisciplinary discussion. Stenting could also be considered in patients who
      have low risk of stroke after stenting (e.g., patients younger than 70 years).
      When a revascularization is indicated, intervention should be done within 2 weeks
      of the index event after TIA or moderate stroke.

PMID- 25595821
TI  - [The transfusion practice in the hepatogastroenterology department of the Campus
      Teaching Hospital of Lome (Togo)].
AB  - OBJECTIVE: To evaluate transfusion practice in the hepatogastroenterology
      department of the Campus Teaching Hospital of Lome. METHODOLOGY: This is a
      respective, descriptive and analytical study conducted from January 1 to December
      31, 2013 on cases of in-patients' observation in the department. The cases of in
      patients of more than 15 years old, having benefited from a blood transfusion
      were included. FINDINGS: During the study period, 849 patients were admitted; 136
      were transfused, or blood transfusion rate of 16.02%. The average age of patients
      was of 48.25 years with extremes of 15 and 90 years. The most transfused rhesus
      blood group was O positive (36.76%). Red blood cell was the most frequently used
      blood product (94.12%). The transfusion was performed in 58.82% of cases as a
      matter of emergency. Gastrointestinal bleeding were the main indications
      (55.88%). The average pre-transfusion hemoglobinemia was 6.51 g/dL+/-1.67. The
      average post-transfusion hemoglobinemia was 8.95 g/dL+/-1.75. Liver disease
      (cirrhosis and hepatocellular carcinoma) were the main diagnosis associated with
      blood transfusion (44.85%). The quantity of blood to be transfused was not
      calculated in 100% of cases. In 11.03% of cases, the compatibility test has not
      been done in the laboratory. Incidents during blood transfusion were noted in 5
      cases. CONCLUSION: Blood transfusion is frequent in the department. There is a
      good observance of blood transfusion safety regulations. However, its practice
      remains to be improved.

PMID- 25595822
TI  - [Thromboelastometric profile of unwashed shed blood after primary knee
      arthroplasty].
AB  - INTRODUCTION: Knee arthroplasty causes significant blood loss. Different blood
      saving measures exist like retransfusion of unwashed salvaged blood. Some studies
      question the quality of this blood and in particular its ability to clot. These
      studies use "static" coagulation tests reflecting only partially the reality,
      unlike viscoelastic methods. The main objective of this study was to evaluate the
      salvaged blood thromboelastometric profile using ROTEM(r) system and to compare
      these results with patient venous blood. MATERIALS AND METHODS: We performed an
      observational, prospective, single-center study conducted over 3 months in 2013.
      Agreement of local ethical committee and patient consent were obtained
      beforehand. All adult patients who underwent a primary total knee arthroplasty
      were included. A thromboelastometric profile and standard laboratory tests
      (hemoglobin, platelets count, PT, aPTT, fibrinogen) were performed in the same
      time on patient venous blood and on unwashed salvaged blood in the PACU. RESULTS:
      Twenty patients were included. The median duration of surgery was 93 minutes.
      Thirteen patients (65%) received tranexamic acid during procedure. The median
      volume of shed blood was 225 mL. Two patients (10%) received a reinfusion.
      Analysis of shed blood showed a major deficiency of clotting factor in standard
      biology (PT<10%) and an absence of clot formation in thromboelastometric test (In
      tem(r), Ex-tem(r), Fib-tem(r) or Ap-tem(r)). Compared to venous blood, shed blood
      had significantly lower hemoglobin levels: 8.8 vs 13.5 g/dL (P<0.0001). Allogenic
      transfusion concerned 5% of patients. DISCUSSION: In this work, we confirmed that
      shed blood was naturally uncoagulable probably due to a multifactorial mechanism
      involving a major clot factor deficiency and an activation of fibrinolysis.

PMID- 25595823
TI  - Deficiency of the Arabidopsis helicase RTEL1 triggers a SOG1-dependent
      replication checkpoint in response to DNA cross-links.
AB  - To maintain genome integrity, DNA replication is executed and regulated by a
      complex molecular network of numerous proteins, including helicases and cell
      cycle checkpoint regulators. Through a systematic screening for putative
      replication mutants, we identified an Arabidopsis thaliana homolog of human
      Regulator of Telomere Length 1 (RTEL1), which functions in DNA replication, DNA
      repair, and recombination. RTEL1 deficiency retards plant growth, a phenotype
      including a prolonged S-phase duration and decreased cell proliferation. Genetic
      analysis revealed that rtel1 mutant plants show activated cell cycle checkpoints,
      specific sensitivity to DNA cross-linking agents, and increased homologous
      recombination, but a lack of progressive shortening of telomeres, indicating that
      RTEL1 functions have only been partially conserved between mammals and plants.
      Surprisingly, RTEL1 deficiency induces tolerance to the deoxynucleotide-depleting
      drug hydroxyurea, which could be mimicked by DNA cross-linking agents. This
      resistance does not rely on the essential replication checkpoint regulator WEE1
      but could be blocked by a mutation in the SOG1 transcription factor. Taken
      together, our data indicate that RTEL1 is required for DNA replication and that
      its deficiency activates a SOG1-dependent replication checkpoint. 

PMID- 25595825
TI  - The mother of underlying causes - economic ranking and health inequality.

PMID- 25595824
TI  - A transient receptor potential ion channel in Chlamydomonas shares key features
      with sensory transduction-associated TRP channels in mammals.
AB  - Sensory modalities are essential for navigating through an ever-changing
      environment. From insects to mammals, transient receptor potential (TRP) channels
      are known mediators for cellular sensing. Chlamydomonas reinhardtii is a motile
      single-celled freshwater green alga that is guided by photosensory,
      mechanosensory, and chemosensory cues. In this type of alga, sensory input is
      first detected by membrane receptors located in the cell body and then transduced
      to the beating cilia by membrane depolarization. Although TRP channels seem to be
      absent in plants, C. reinhardtii possesses genomic sequences encoding TRP
      proteins. Here, we describe the cloning and characterization of a C. reinhardtii
      version of a TRP channel sharing key features present in mammalian TRP channels
      associated with sensory transduction. In silico sequence-structure analysis
      unveiled the modular design of TRP channels, and electrophysiological experiments
      conducted on Human Embryonic Kidney-293T cells expressing the Cr-TRP1 clone
      showed that many of the core functional features of metazoan TRP channels are
      present in Cr-TRP1, suggesting that basic TRP channel gating characteristics
      evolved early in the history of eukaryotes. 

PMID- 25595826
TI  - Accuracy and progress in the analytics of pharmaceuticalization: a response to
      Davis (2014).
AB  - This commentary considers the important contribution to understanding
      pharmaceuticalization made by Davis's (2014) case study of cancer drug treatment
      in end-of-life-care. However, it argues that Davis (2014) has misunderstood some
      aspects of the conceptual and analytical framework put forward by Abraham (2010)
      as a way of explaining the nature and implications of pharmaceuticalization. 

PMID- 25595827
TI  - Management of the axilla: has Z0011 had an impact?
AB  - BACKGROUND: Management of axillary disease in breast cancer has evolved
      significantly over the last two decades with the introduction of SLNB and a trend
      towards less radical surgery. Data from the American College of Surgeons Oncology
      Group Z0011 trial proposes that not all patients with positive axillary lymph
      nodes require completion axillary dissection. AIMS: The aim of this study was to
      determine whether there has been a change in practice patterns for axillary
      management in Ireland since the publication of this 'practice-changing' trial.
      METHODS: A review of breast cancers managed in the 12 months prior to publication
      of Z0011 (pre-Z0011) and comparison with those managed in the following 12 months
      (post-Z0011) was undertaken in three tertiary referral breast cancer centres.
      Patients with a positive SLNB were identified, and clinicopathologic data and
      subsequent management was compared between the two cohorts. RESULTS: There were
      708 SLNB performed during the study period; 326 pre-Z0011 and 382 post-Z0011.
      There was no difference in the rate of SLN positivity between the two cohorts:
      29.1 % had a positive SLN pre-Z0011 and 29.3 % were positive post-Z0011. There
      were a significantly lower number of axillary clearances performed in SLN
      positive patients in the post-Z0011 period (71.4 %) compared to the pre-Z011
      period (93.7 %, p = 0.0022 Chi-square). Of the patients with tumour
      characteristics meeting the Z0011 inclusion criteria in the initial 12 months of
      the study, 92.3 % underwent ALND compared with 65.6 % in the final 12 months of
      the study (p = 0.0006 Chi-square). CONCLUSIONS: There has been a change in
      clinical practice since the publication of the Z0011 trial, illustrated by a
      decrease in the rate of axillary clearance in node-positive breast cancers.

PMID- 25595828
TI  - Report on the creation of a diabetes register and retinopathy screening outcomes
      in the Mid-West of Ireland.
AB  - BACKGROUND: With concerns that blind registration in Ireland due to diabetic
      retinopathy is continuing to rise, a structured retinopathy screening service is
      in the process of being rolled out nationally. AIMS: To report on the validation
      process for creating a register of diabetics in the Mid-West of Ireland, and
      findings following retinopathy screening of a representative sample. METHODS:
      National primary care databases were employed in generating provisional lists of
      diabetic patients in the Health Service Executive (HSE) Mid-West area. Subsequent
      engagement with the corresponding general practices over a three year period
      between 2010 and 2013 facilitated the validation of these lists. A summary of the
      retinopathy screening outcomes of 1,434 patients and pre-existing screening
      patterns is reported. RESULTS: The number of patients on the Mid-West diabetes
      register to date is 11,126. Of the 1,434 patients screened, 288 (20.1 %) had
      background retinopathy, while 117 (8.2 %) had sight-threatening retinopathy.
      Seventeen (19.8 %) of the 86 patients identified with maculopathy required
      treatment with intravitreal injections. Of the 610 patients questioned about
      previous screening events, 389 (63.8 %) said they had undergone an ocular
      examination within the previous 12 months. CONCLUSIONS: The HSE Mid-West has over
      11,000 patients on its database ready to be screened by the national programme,
      with the treatment of maculopathy expected to have the largest impact on
      resources. Although the majority of patients are already undergoing screening in
      the community in an ad hoc fashion, the rates of sight-threatening retinopathy
      encountered highlight the timeliness of the full implementation of the national
      programme.

PMID- 25595829
TI  - "Top Gun" competition: motivation and practice narrows the technical skill gap
      among new cardiothoracic surgery residents.
AB  - BACKGROUND: Adoption of simulation skills training in cardiothoracic (CT) surgery
      remains a challenge. This study sought to determine whether a "Top Gun"
      competition would encourage simulator use and improve technical skills among
      first-year CT residents. METHODS: A coronary anastomosis simulation module with
      instructional video was sent to 96 first-year CT residents in traditional
      programs who were then invited to participate in a Top Gun competition. Residents
      uploaded a video recording of their baseline anastomosis using the simulator.
      After 6 weeks of practice under faculty supervision, each trainee uploaded a
      final video. All submissions were rated in blinded fashion by three CT surgeons.
      Twelve components were scored on a 5-point Likert scale (1 = poor; 5 =
      excellent); also, an overall pass-fail grade was given. Five trainees with the
      highest final scores were invited to compete at a live Top Gun competition.
      RESULTS: Seventeen trainees submitted a baseline anastomosis video for
      evaluation; 15 submitted a final video. Overall average scores improved from 3.24
      +/- 0.61 to 4.01 +/- 0.33 (p < 0.001). Performance of the bottom 50% increased
      (1.11 +/- 0.57) relative to the top 50% (0.43 +/- 0.31), resulting in no
      detectable score difference after training (p = 0.14). Overall average time
      (minutes:seconds) decreased from 11:10 (range, 5:56 to 18:58) to 9:04 (range,
      5:52 to 16:23; p < 0.01). Residents achieving a pass from all three raters
      increased from 13% (2 of 15) to 73% (11 of 15; p < 0.002). Thirteen of 15
      residents completed a survey. Residents performed an average of 23 anastomoses
      (range, 10 to 40). The majority (10 of 13) agreed or strongly agreed that
      practicing on simulators will improve a trainee's technical skill acquisition.
      CONCLUSIONS: Focused training results in improved technical skills in vessel
      anastomosis, especially for residents with lower baseline skills. Simulation, as
      with any educational endeavor, requires the motivation of the trainee, commitment
      of the faculty educator, and a defined training curriculum.

PMID- 25595830
TI  - Neutrophil gelatinase-associated lipocalin as early predictor of acute kidney
      injury after cardiac surgery in adults with chronic kidney failure.
AB  - BACKGROUND: To assess the utility of neutrophil gelatinase-associated lipocalin
      (NGAL) as an early marker of acute kidney injury (AKI) occurring after cardiac
      surgery in patients with prior chronic kidney failure. METHODS: Patients with
      preoperative creatinine clearance 60 mL * min(-1) * 1.73 m(-2) or less according
      to the Cockcroft-Gault formula and scheduled to undergo cardiac surgery were
      eligible for inclusion. The AKI was defined as an increase in plasma creatinine
      greater than 50% over preoperative values. Threshold values of NGAL predictive of
      AKI were determined using receiver operating characteristic curve analysis, and
      predictive value of NGAL for AKI was evaluated by logistic regression. RESULTS:
      Over a 1-year inclusion period, 166 patients were included. At 6 hours post
      surgery, hypertension, occurrence of at least 1 postoperative complication, and
      NGAL greater than 155 ng/mL were shown to be independent predictors of AKI. NGAL
      greater than 155 ng/mL at 6 hours was associated with an odds ratio for risk of
      postoperative AKI of 7.1 [2.7 to 18]. On average, diagnosis of postoperative AKI
      was made 20 hours earlier using NGAL at 6 hours post-surgery as compared with a
      diagnosis based on a 50% increase in creatinine over baseline. The threshold for
      NGAL of 155 ng/mL at 6 hours had a sensitivity of 79% and specificity of 58% for
      the diagnosis of AKI. CONCLUSIONS: Earlier diagnosis of AKI post-surgery based on
      NGAL assessment makes it possible to initiate appropriate therapy at an earlier
      stage in this high-risk patient population.

PMID- 25595831
TI  - Heterotaxy syndrome infants are at risk for early shunt failure after Ladd
      procedure.
AB  - BACKGROUND: Cardiac-specific risks and complications after a Ladd procedure in
      patients with heterotaxy syndrome (HS) and intestinal rotational anomalies (IRA)
      are unknown. We sought to (1) describe rates of hospital mortality and early
      systemic-to-pulmonary (S-P) artery shunt failure after the Ladd procedure in
      patients with HS and (2) explore risk factors associated with early shunt failure
      in patients with HS with single ventricle (SV). METHODS: This retrospective study
      included all Ladd procedures performed from January 1999 to December 2012 in
      patients with HS at a single center. Risk factors investigated for early S-P
      artery shunt failure included birth weight, gestational age, sex, age at and
      timing of Ladd procedure relative to cardiac operations, and shunt type. RESULTS:
      Ladd procedure was performed on 54 infants with HS and congenital heart disease.
      Hospital mortality for the entire cohort was 5.6% (3 of 54 patients). Early shunt
      failure occurred in 19% (4 of 21) of HS infants with SV. Mean preoperative blood
      urea nitrogen (BUN) levels were higher in HS infants with early shunt failure (20
      versus 12.5 mg/dL; p = 0.054). CONCLUSIONS: Patients with SV and HS with S-P
      artery shunts are at risk for early shunt failure after a Ladd procedure. A
      higher mean preoperative BUN level is noted in patients with HS and early shunt
      failure. Careful risk-benefit analysis is indicated before recommending routine
      elective Ladd procedures in patients with HS.

PMID- 25595832
TI  - Lessons from an outbreak of metallo-beta-lactamase-producing Klebsiella oxytoca
      in an intensive care unit: the importance of time at risk and combination
      therapy.
AB  - BACKGROUND: Outbreaks of nosocomial infection due to carbapenem-resistant
      Enterobacteriaceae (CRE), mostly Klebsiella spp., have become a worldwide
      phenomenon. AIM: To investigate the risk factors for the acquisition of clonal
      multidrug-resistant Klebsiella oxytoca (MDRKO) producing the metallo-beta
      lactamase IMP-8 and hyperproducing chromosomal OXY-2 beta-lactamase during a well
      characterized outbreak, and to describe the clinical features of infections due
      to MDRKO. METHODS: A four-wave outbreak due to MDRKO occurred in the intensive
      care unit of a Spanish hospital between 2009 and 2011. The risk factors for
      acquisition of MDRKO during waves 1 and 2 (in which colonized patients served as
      the main reservoir for the epidemic strain) were analysed using a case-control
      study by Cox regression and logistic regression analysis. Clinical data and
      treatments of patients infected with MDRKO were also analysed. FINDINGS: For the
      study of risk factors, 26 cases and 45 controls were studied. None of the
      variables studied in the Cox regression analysis showed an association with MDRKO
      acquisition; time at risk was the only associated variable by logistic regression
      analysis. Colonization pressure was not associated with earlier acquisition.
      Overall, 14 patients were infected with MDRKO; ventilator-associated pneumonia
      (seven patients) was the most frequent type of infection. Monotherapy tended to
      be associated with higher mortality than combination therapy [60% (3/5) vs 16.6%
      (1/6); P = 0.07]. CONCLUSIONS: Time at risk was the most significant risk
      determinant for the acquisition of carbapenem-resistant Enterobacteriaceae (CRE)
      in this epidemiological context and should be included in any study of risk
      factors for the acquisition of multidrug-resistant bacteria. Combination therapy
      may be superior to monotherapy for the treatment of CRE infections.

PMID- 25595833
TI  - Transmission of antimicrobial resistance in resource-poor healthcare.
AB  - Inter-patient transfer of antimicrobial resistant pathogens is more common in
      resource-poor healthcare settings. In this age of global resistance, what
      contributes to the spread of antimicrobial resistant clones? 

PMID- 25595834
TI  - A validated UHPLC-MS/MS method to quantify low levels of anabolic-androgenic
      steroids naturally present in urine of untreated horses.
AB  - Doping control is a main priority for regulatory bodies of both the horse racing
      industry and the equestrian sports. Urine and blood samples are screened for the
      presence of hundreds of forbidden substances including anabolic-androgenic
      steroids (AASs). Based on the suspected endogenous origin of some AASs, with beta
      boldenone as the most illicit candidate, this study aimed to improve the
      knowledge of the naturally present AAS in horse urine. To this extent, a novel
      ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS) method was developed and validated according to the Association of
      Official Racing Chemists (AORC) and European Commission (EC) guidelines, proving
      the power of this new method. Low limits of detection (0.2 ng/mL), good
      reproducibility (percentage of standard deviation (%RSD) < 10%), high recovery
      (94.6 to 117.1%), selectivity and specificity, and a linear response (confirmed
      with R(2) > 0.99 and lack-of-fit analysis) were obtained for all included AASs.
      With this method, urine samples of 105 guaranteed untreated horses (47 geldings,
      53 mares, and 5 stallions serving as a control) were screened for beta-boldenone
      and five related natural steroids: androstadienedione (ADD), androstenedione
      (AED), alpha-testosterone (alphaT), beta-testosterone (betaT), and progesterone
      (P). Progesterone, beta-testosterone, and alpha-testosterone were detected in
      more than half of the horses at low concentrations (<2 ng/mL). Occasionally, not
      only testosterone and progesterone but also low concentrations of AED, ADD, and
      boldenone (Bol) were found (0.5-5 ng/mL). Graphical Abstract A sensitive, new and
      fully validated UHPLC-MS/MS method has been developed that is able to quantify
      low levels of anabolic-androgenic steroids naturally present in urine of
      untreated horses (mares and geldings).

PMID- 25595837
TI  - Control of the basement membrane and cell migration by ADAMTS proteinases:
      Lessons from C. elegans genetics.
AB  - The members of the ADAMTS (a disintegrin and metalloproteinase with
      thrombospondin motifs) family of secreted proteins, MIG-17 and GON-1, play
      essential roles in Caenorhabditis elegans gonadogenesis. The genetic and
      molecular analyses of these proteinases uncovered novel molecular interactions
      regulating the basement membrane (BM) during the migration of the gonadal leader
      cells. MIG-17, which is localized to the gonadal BM recruits or activates fibulin
      1 and type IV collagen, which then recruits nidogen, thereby inducing the
      remodeling of the BM that is required for directional control of leader cell
      migration. GON-1 acts antagonistically with fibulin-1 to regulate the levels of
      type IV collagen accumulation in the gonadal BM, which facilitates active
      migration of the leader cells. The cooperative action of MIG-17 and GON-1
      represents an excellent model for understanding the mechanisms of organogenesis
      mediated by ADAMTS proteinases. 

PMID- 25595838
TI  - "EndoFLIP" in assessment of esophagogastric junction distensibility prior to and
      during per oral endoscopic myotomy.

PMID- 25595835
TI  - Histology-directed and imaging mass spectrometry: An emerging technology in
      ectopic calcification.
AB  - The present study was designed to demonstrate the potential of an optimized
      histology directed protein identification combined with imaging mass spectrometry
      technology to reveal and identify molecules associated to ectopic calcification
      in human tissue. As a proof of concept, mineralized and non-mineralized areas
      were compared within the same dermal tissue obtained from a patient affected by
      Pseudoxanthoma elasticum, a genetic disorder characterized by calcification only
      at specific sites of soft connective tissues. Data have been technically
      validated on a contralateral dermal tissue from the same subject and compared
      with those from control healthy skin. Results demonstrate that this approach 1)
      significantly reduces the effects generated by techniques that, disrupting tissue
      organization, blend data from affected and unaffected areas; 2) demonstrates
      that, abolishing differences due to inter-individual variability, mineralized and
      non-mineralized areas within the same sample have a specific protein profile and
      have a different distribution of molecules; and 3) avoiding the bias of focusing
      on already known molecules, reveals a number of proteins that have been never
      related to the disease nor to the calcification process, thus paving the way for
      the selection of new molecules to be validated as pathogenic or as potential
      pharmacological targets. 

PMID- 25595839
TI  - Small bowel diaphragm disease.

PMID- 25595840
TI  - Tumor-associated macrophages as an emerging target against tumors: Creating a new
      path from bench to bedside.
AB  - Tumor-associated macrophages are a critical component of tumor microenvironments,
      which affect tumor growth, tumor angiogenesis, immune suppression, metastasis and
      chemoresistance. There is emerging evidence that many anticancer modalities
      currently used in the clinic have unique and distinct properties that modulate
      the recruitment, polarization and tumorigenic activities of macrophages in the
      tumor microenvironments. Educated tumor-associated macrophages significantly
      impact the clinical efficacies of and resistance to these anticancer modalities.
      Moreover, the development of drugs targeting tumor-associated macrophages,
      especially c-Fms kinase inhibitors and humanized antibodies targeting colony
      stimulating factor-1 receptor, are in early clinical stages and show promising
      benefit for cancer patients. These experimental and clinical findings prompted us
      to further evaluate the potential targets that exhibit tumorigenic and
      immunosuppressive potential in a manner specific for tumor associated
      macrophages. 

PMID- 25595836
TI  - New strategies for targeting matrix metalloproteinases.
AB  - The development of matrix metalloproteinase (MMP) inhibitors has often been
      frustrated by a lack of specificity and subsequent off-target effects. More
      recently, inhibitor design has considered secondary binding sites (exosites) to
      improve specificity. Small molecules and peptides have been developed that bind
      exosites in the catalytic (CAT) domain of MMP-13, the CAT or hemopexin-like (HPX)
      domain of MT1-MMP, and the collagen binding domain (CBD) of MMP-2 and MMP-9.
      Antibody-based approaches have resulted in selective inhibitors for MMP-9 and MT1
      MMP that target CAT domain exosites. Triple-helical "mini-proteins" have taken
      advantage of collagen binding exosites, producing a family of novel probes. A
      variety of non-traditional approaches that incorporate exosite binding into the
      design process has yielded inhibitors with desirable selectivities within the MMP
      family. 

PMID- 25595841
TI  - Is the vigilance regulation model of affective disorders and ADHD also
      appropriate for other psychiatric disorders (schizophrenia, autism) and is it
      associated with glutamate?

PMID- 25595842
TI  - Diagnostic pitfalls in Clostridium difficile infection.
AB  - Accurate diagnosis of Clostridium difficile infection (CDI) is important not only
      for patient care but also for epidemiology and disease research. As it is not
      possible clinically to reliably differentiate CDI from other causes of health
      care-associated diarrhea, the laboratory confirmation of CDI is essential. Rapid
      commercial assays, including nucleic acid amplification tests and immunoassays
      for C difficile toxin and glutamate dehydrogenase, have largely superseded the
      use of older assays. Although assays that detect the presence of free C difficile
      toxin in feces are less frequently positive than tests for organism, they are
      preferable for the detection of CDI. 

PMID- 25595843
TI  - Colonization versus carriage of Clostridium difficile.
AB  - Asymptomatic carriage of toxigenic strains of Clostridium difficile is common in
      health care facilities and the community. However, infection control efforts have
      traditionally focused almost entirely on symptomatic patients. There is now
      growing concern that asymptomatic carriers may be an underappreciated source of
      transmission. This article provides an overview of the pathogenesis and
      epidemiology of C difficile colonization, reviews the evidence that asymptomatic
      carriers shed spores and contribute to transmission, and examines practical
      issues related to prevention of transmission from carriers. 

PMID- 25595845
TI  - Stability of bacterial carotenoids in the presence of iron in a model of the
      gastric compartment - comparison with dietary reference carotenoids.
AB  - Recently isolated spore-forming pigmented marine bacteria, Bacillus indicus HU36
      and Bacillus firmus GB1 are sources of carotenoids (~fifteen distinct yellow and
      orange pigments and ~thirteen distinct pink pigments, respectively). They are
      glycosides of oxygenated lycopene derivatives (apo-lycopenoids) and are assumed
      to be more heat- and gastric-stable than common carotenoids. In this study, the
      oxidation by O2 of the bacterial carotenoids was initiated by free iron (Fe(II)
      and Fe(III)) or by heme iron (metmyoglobin) in a mildly acidic aqueous solution
      mimicking the gastro-intestinal compartment and compared to the oxidation of the
      common dietary carotenoids beta-carotene, lycopene and astaxanthin. Under these
      conditions, all bacterial carotenoids appear more stable in the presence of heme
      iron vs. free iron. Carotenoid autoxidation initiated by Fe(II) is relatively
      fast and likely involves reactive oxygen-iron species derived from Fe(II) and O2.
      By contrast, the corresponding reaction with Fe(III) is kinetically blocked by
      the slow preliminary reduction of Fe(III) into Fe(II) by the carotenoids. The
      stability of carotenoids toward autoxidation increases as follows: beta
      carotene<lycopene<astaxanthin<HU36 and GB1. In particular, bacterial carotenoids
      react more quickly than reference carotenoids with Fe(III), but much more slowly
      than the reference carotenoids with Fe(II). This reaction is correlated with the
      structure of the carotenoids, which can have opposite effects in a micellar
      system: bacterial carotenoids with electro-attracting terminal groups have a
      lower reducing capacity than beta-carotene and lycopene. However, their polar
      head favours their location close to the interface of micelles, in closer contact
      with oxidative species. Kinetic analyses of the iron-induced autoxidation of
      astaxanthin and HU36 carotenoids has been performed and gives insights in the
      underlying mechanisms.

PMID- 25595847
TI  - Balancing the personal, local, institutional, and global: multiple case study and
      multidimensional scaling analysis of African experiences in addressing complexity
      and political economy in health research capacity strengthening.
AB  - BACKGROUND: Strengthening health research capacity in low- and middle-income
      countries remains a major policy goal. The Health Research Capacity Strengthening
      (HRCS) Global Learning (HGL) program of work documented experiences of HRCS
      across sub-Saharan Africa. METHODS: We reviewed findings from HGL case studies
      and reflective papers regarding the dynamics of HRCS. Analysis was structured
      with respect to common challenges in such work, identified through a multi
      dimensional scaling analysis of responses from 37 participants at the concluding
      symposium of the program of work. RESULTS: Symposium participants identified 10
      distinct clusters of challenges: engaging researchers, policymakers, and donors;
      securing trust and cooperation; finding common interest; securing long-term
      funding; establishing sustainable models of capacity strengthening; ensuring
      Southern ownership; accommodating local health system priorities and constraints;
      addressing disincentives for academic engagement; establishing and retaining
      research teams; and sustaining mentorship and institutional support. Analysis
      links these challenges to three key and potentially competing drivers of the
      political economy of health research: an enduring model of independent
      researchers and research leaders, the globalization of knowledge and the linked
      mobility of (elite) individuals, and institutionalization of research within
      universities and research centres and, increasingly, national research and
      development agendas. CONCLUSIONS: We identify tensions between efforts to embrace
      the global 'Community of Science' and the promotion and protection of national
      and institutional agendas in an unequal global health research environment. A
      nuanced understanding of the dynamics and implications of the uneven global
      health research landscape is required, along with a willingness to explore
      pragmatic models that seek to balance these competing drivers.

PMID- 25595846
TI  - CADASIL with a novel NOTCH3 mutation (Cys478Tyr).
AB  - Recently, an increasing number of NOTCH3 mutations have been described to cause
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL). Here, we report 2 CADASIL patients from a Japanese
      family, who were found to possess a novel NOTCH3 mutation. The proband only had
      chronic headache, and her mother had previously suffered a minor stroke. Although
      the patients' clinical symptoms were mild, their distinctive magnetic resonance
      imaging (MRI) features suggested CADASIL. Genetic analysis revealed that both
      patients had a novel heterozygous NOTCH3 mutation (p.Cys478Tyr) leading to
      stereotypical cysteine loss. The present finding suggests that genetic testing
      for NOTCH3 mutations in patients with distinctive MRI features, even if the
      symptoms are as mild as chronic headache, should help to broaden the mutational
      and clinical spectrum of CADASIL. 

PMID- 25595848
TI  - Reproductive health services utilization and its associated factors among
      Madawalabu University students, Southeast Ethiopia: cross-sectional study.
AB  - BACKGROUND: Youths in Sub-Saharan region including Ethiopia account for higher
      proportion of new HIV infections, maternal mortality ratios, and unmet need for
      reproductive health information and services. This study assessed reproductive
      health services utilization and its associated factors among Madawalabu
      University Students, Southeast Ethiopia. METHODS: Institutional-based cross
      sectional study was conducted among regular under graduate Madawalabu University
      students in May 2014. Data were collected from randomly selected students through
      self-administered pre-tested structured questionnaire. Data were entered in to
      EpiData 3.1 and exported to SPSS-16.0 for analysis. Descriptive, bivariate and
      multivariate analyses were employed. RESULT: From the total 568 respondents
      507(89.3%) of them knew modern family planning. 457(80.5%) of them had ever
      utilized at least one reproductive health services. Students who ever made
      discussion on VCT with health profession utilized the VCT two times than those
      hadn't made discussion (AOR 2.06, 95% CI 1.21-3.48). Discussion also triple
      reproductive health services utilization (AOR 3.76, CI 1.55-9.11). CONCLUSION:
      Utilization of reproductive health services for the three indexed variables
      namely: modern contraceptives, STI diagnosis and treatment, and VCT is fair. But
      utilization of specific reproductive health services is under expectation.
      Discussion on reproductive health services between health worker and students,
      and focusing other identified factors are the way of reproductive health problems
      intervention in the University.

PMID- 25595849
TI  - Intramedullary spinal cord neurocysticercosis presenting as Brown-Sequard
      syndrome.
AB  - BACKGROUND: Cysticercosis is a parasitic disease caused by the larval stage of
      Taenia Solium. Involvement of the central nervous system by this tapeworm is
      endemic in developing countries. However, isolated spinal involvement by Taenia
      Solium is uncommon and having clinical presentation of Brown-Sequard syndrome is
      even rarer. CASE PRESENTATION: A 43-year-old male who came to the emergency
      department with clinical presentation of complete Brown-Sequard syndrome.
      Computed tomography scan of the brain was normal. Magnetic resonance imaging of
      the thoracic spine revealed an intramedullary mass of the spinal cord at C-7/T-l
      level. Patient underwent surgery that revealed a cystic lesion and was resected.
      Histopathological report confirmed the diagnosis of neurocysticercosis.
      Postoperatively, oral steroid therapy and a four week course of albendazol were
      administered. CONCLUSIONS: Intramedullary neurcysticercosis represents a
      diagnostic challenge and should be considered in intramedullary lesions in
      settings where Taenia solium is endemic. Clinical, pathophysiological and
      diagnostic aspects of spinal cord intramedullary neurocysticercosis are
      discussed.

PMID- 25595850
TI  - Correlation between vascular endothelial growth factor expression and presence of
      lymph node metastasis in advanced squamous cell carcinoma of the larynx.
AB  - INTRODUCTION: Squamous cell carcinoma is the most common neoplasm of the larynx,
      and its evolution depends on tumor staging. Vascular endothelial growth factor is
      a marker of angiogenesis, and its expression may be related to increased tumor
      aggressiveness, as evidenced by the presence of cervical lymphatic metastases.
      OBJECTIVES: To evaluate the expression of the vascular endothelial growth factor
      marker in non-glottic advanced squamous cell carcinoma of the larynx (T3/T4) and
      correlate it with the presence of cervical lymph node metastases. METHODS:
      Retrospective clinical study and immunohistochemical analysis of vascular
      endothelial growth factor through the German scale of immunoreactivity in
      products of non-glottic squamous cell carcinomas. RESULTS: This study analyzed 15
      cases of advanced non-glottic laryngeal tumors (T3/T4), four of which exhibited
      cervical lymphatic metastases. There was no correlation between vascular
      endothelial growth factor expression and the presence of cervical metastases.
      CONCLUSION: Although vascular endothelial growth factor was expressed in a few
      cases, there was no correlation with the spread of cervical lymph metastases.

PMID- 25595851
TI  - Evaluation of the nasal shape after orthognathic surgery.
AB  - INTRODUCTION: Patients with dentofacial deformities may benefit from orthognathic
      surgery in the maxilla. Maxillary osteotomy may include procedures in the bone,
      cartilaginous, and soft tissues of the nose, leading to shape alterations.
      OBJECTIVE: To evaluate the anatomic alterations of the nasal region in patients
      undergoing a Le Fort I osteotomy for advancement or superior impaction. METHODS:
      This is a clinical prospective study. Twenty-one patients were evaluated during
      the pre- and postoperative periods. The positioning of the nasal tip and the
      modification of the nasal base were evaluated. RESULTS: The results showed that
      the nasal tip was superiorly positioned in 85% of the cases, advanced in 80%,
      rotated in 80%, and there was a wide nasal base in 95%, resulting in esthetic
      improvement. CONCLUSIONS: Surgeries of maxillary advancement and superior
      reposition tend to cause elevation and advancement of the nasal tip, as well as
      enlargement of the nasal base.

PMID- 25595852
TI  - Post-term birth as a response to environmental stress : The case of September 11,
      2001.
AB  - BACKGROUND AND OBJECTIVES: Despite growing interest in the role of maternal
      psychosocial stress as a determinant of preterm birth, no existing work has
      examined the relation between maternal stress and post-term birth (>=42 weeks).
      We hypothesize that prolonging gestation past term may represent an adaptive
      strategy to a suboptimal environment. METHODOLOGY: We examined the relationship
      between exposure to the September 2001 terrorist attacks and odds of post-term
      birth in California. We calculated the expected odds of post-term birth among
      conception cohorts of singleton gestations in California between October 1996 and
      November 2005. We used time series analysis to test for higher than expected odds
      of post-term birth among the 10 cohorts exposed to the attacks of September 2001
      (those conceived from December 2000 to September 2001). RESULTS: The observed
      odds of post-term delivery among gestations at 33-36 weeks in September 2001 were
      higher than statistically expected for all race/ethnic and sex groups.
      CONCLUSIONS AND IMPLICATIONS: Our finding that odds of post-term birth were
      higher than expected among pregnancies exposed to the September 2001 terrorist
      attacks in late gestation provides initial support for the hypothesis that
      exposure to a psychosocial stress during pregnancy may result in prolonged
      gestation.

PMID- 25595854
TI  - Development of the splanchnocranium in Prochilodus argenteus (Teleostei:
      Characiformes) with a discussion of the basal developmental patterns in the
      Otophysi.
AB  - Development of the mandibular, hyoid and gill arches, which constitute the
      splanchnocranium, are described for Prochilodus argenteus, order Characiformes,
      one of the basal lineages of the Otophysi. Development was examined from just
      hatched larvae through juveniles using whole specimens cleared and counterstained
      for cartilage and bone as well as histological preparations. Observations are
      compared with the developmental trends reported for Cypriniformes, the basalmost
      clade of the Otophysi. Shortened developmental sequences for Prochilodus compared
      to the cypriniform Catostomus were discovered in the ontogeny of the ceratohyals,
      ceratobranchials 1-5, epibranchials 1-4 and the symplectic portion of the
      hyosymplectic. Prochilodus also differs from Catostomus in having the basihyal
      plus the anterior copula appearing at different stages of ontogeny rather than
      simultaneously. Contrary to previous assumptions, developmental information
      indicates that hypobranchial 4 as well as likely basibranchial 5 are present in
      Prochilodus. Various developmental patterns in Prochilodus considered basal for
      the Otophysi, the predominant component of the Ostariophysi, are likely conserved
      from patterns prevalent in basal groups in the Actinopterygii. 

PMID- 25595853
TI  - Genome-wide microRNA expression profiling in placentas of fetuses with Down
      syndrome.
AB  - INTRODUCTION: Down syndrome (DS) is the most common aneuploidy, caused by an
      extra copy of all or part of chromosome 21 (chr21). Differential microRNA (miRNA)
      expression is involved in many human diseases including DS. However, the genome
      wide changes in miRNA expression in DS fetal placentas have yet to be determined,
      and the function of these changes is also unclear. METHODS: We profiled genome
      wide miRNA expression in placenta samples from euploid or DS fetuses by using
      microarray technology and predicted the functions of differentially expressed
      miRNAs using bioinformatics tools. RESULTS: Thirty-four miRNAs were significantly
      differentially expressed in the DS placenta compared with the normal placenta (16
      up-regulated and 18 down-regulated). However, expression of chr21-derived miRNAs
      did not change. Predicted target genes included 7434 genes targeted by up
      regulated miRNAs and 6071 genes targeted by down-regulated miRNAs. Seventy-six of
      these target genes were located on chr21 (10 genes controlled by down-regulated
      miRNAs and 34 genes by up-regulated miRNAs, and 32 genes by both). Target genes
      on chr21 were significantly associated with DS and DS-related disorders, such as
      mental retardation, neurobehavioral manifestations, and congenital abnormalities.
      DISCUSSION: To our knowledge, this is the first genome-wide study to
      comprehensively survey placental miRNAs in DS fetuses. Our results provide new
      insight into miRNA expression in placentas of fetuses with DS. Additionally, our
      findings indicate that the differentially expressed miRNAs in the DS placenta may
      potentially affect various pathways related to DS pathogenesis.

PMID- 25595855
TI  - [The cardiovascular surgeon and the Syntax score].
AB  - The Syntax score has been established as a tool to determine the complexity of
      coronary artery disease and as a guide for decision-making among coronary artery
      bypass surgery and percutaneous coronary intervention. The purpose of this review
      is to systematically examine what the Syntax score is, and how the surgeon should
      integrate the information in the selection and treatment of patients. We reviewed
      the results of the SYNTAX Trial, the clinical practice guidelines, as well as the
      benefits and limitations of the score. Finally we discuss the future directions
      of the Syntax score.

PMID- 25595856
TI  - The computation of relative numerosity, size and density.
AB  - To investigate the mechanisms for the perception of relative numerosity, we used
      two-interval forced-choice (temporal 2AFC) to measure thresholds for area,
      density and numerosity differences between dot textures, and a 2*2 FC task to
      measure the ability of observers to distinguish changes in area from changes in
      density. To prevent the use of a one-dimensional size signal we used textures in
      which dots were scattered within irregular polygonal areas. Numerosity thresholds
      were similar in the area and density-varying conditions, consistent with a single
      numerosity mechanism. Thresholds for area and density discriminations were raised
      when number was held constant, consistent with numerosity thresholds being lower
      than those for size and density. Also, area thresholds for polygonal outlines
      were increased when no dots were present in the outline. However, a single
      numerosity mechanism cannot account for all the data, because we find that
      observers in randomly-interleaved size-varying and density-varying conditions are
      also able to discriminate between changes in size and density with a precision
      predicted from independently-noisy size and density channels that have similar
      noise to that in the putative numerosity channel. A complication, previously
      noted with circular shapes, is that denser textures tend to be confused with
      larger textures, and vice versa. This could explain why thresholds rise when
      density and size changes are in opposition, in the constant-number case. These
      findings taken together do not rule out an independent numerosity mechanism, but
      they are equally compatible with a flexible computation of numerosity from size
      and density cues.

PMID- 25595857
TI  - The effect of contrast polarity reversal on face detection: evidence of
      perceptual asymmetry from sweep VEP.
AB  - Contrast polarity inversion (i.e., turning dark regions light and vice versa)
      impairs face perception. We investigated the perceptual asymmetry between
      positive and negative polarity faces (matched for overall luminance) using a
      sweep VEP approach in the context of face detection (Journal of Vision 12 (2012)
      1-18). Phase-scrambled face stimuli alternated at a rate of 3 Hz (6 images/s).
      The phase coherence of every other stimulus was parametrically increased so that
      a face gradually emerged over a 20-s stimulation sequence, leading to a 3 Hz
      response reflecting face detection. Contrary to the 6 Hz response, reflecting low
      level visual processing, this 3 Hz response was larger and emerged earlier over
      right occipito-temporal channels for positive than negative polarity faces.
      Moreover, the 3 Hz response emerged abruptly to positive polarity faces, whereas
      it increased linearly for negative polarity faces. In another condition,
      alternating between a positive and a negative polarity face also elicited a
      strong 3 Hz response, indicating an asymmetrical representation of positive and
      negative polarity faces even at supra-threshold levels (i.e., when both stimuli
      were perceived as faces). Overall, these findings demonstrate distinct perceptual
      representations of positive and negative polarity faces, independently of low
      level cues, and suggest qualitatively different detection processes (template
      based matching for positive polarity faces vs. linear accumulation of evidence
      for negative polarity faces).

PMID- 25595858
TI  - What evidence is there for the use of workplace-based assessment in surgical
      training?

PMID- 25595859
TI  - Differences in duty hours and their relationship with academic parameters between
      preliminary and categorical general surgery residents.
AB  - BACKGROUND: There is the perceived notion that nondesignated preliminary general
      surgery (P-GS) interns are treated differently (i.e., overworked) than their
      categorical GS (C-GS) counterparts are treated, or in an effort to prove
      themselves worthy of a categorical position, nondesignated preliminary residents
      may self-choose to work more. Empirical evidence examining duty-hour differences
      between P-GS and C-GS residents is lacking. METHODS: We retrospectively reviewed
      4 academic years (July 2009 to June 2013) of our self-entered duty-hour database.
      Duty hours were averaged over 4-week periods and then averaged annually for each
      intern. Duty-hour averages and the percentage of conference attendance between P
      GS and C-GS interns were compared. Sensitivity analyses were conducted to
      evaluate the effect of the 2011 duty-hour regulations, attendance to educational
      activities, seasonal variations in workload, and the Match Day effect. RESULTS: A
      total of 70 P-GS and 43 C-GS interns were compared. Duty-hour averages (+/
      standard deviation, range) were 64.4h/wk (+/-4.6; 45-70) for the P-GS interns and
      64.1h/wk (+/-3.9; 57-72) for the C-GS interns, p = 0.8. Mean (+/-standard
      deviation, range) conference attendance was 61% (+/-17; 33-89) for the P-GS
      interns and 66% (+/-18; 44-85) for the C-GS interns (p = 0.13). Duty-hour
      averages for both the groups positively correlated with conference attendance (r
      = 0.27, p = <0.001). The P-GS and the C-GS interns worked on average 4.8 hours
      more a week after the implementation of the 2011 Accreditation Council of
      Graduate Medical Education duty-hour regulations when compared with before
      implementation (66.7 +/- 4.1 vs 62 +/- 3.1, p < 0.0001), with no difference
      between both the groups. No seasonal variation in duty hours was encountered for
      either group. For the P-GS interns, no difference in duty hours was observed
      before or after the Match Day. CONCLUSIONS: At our institution, the P-GS and the
      C-GS interns have equivalent duty-hour periods and similar conference attendance.
      An expected, a positive correlation was observed between duty hours and
      conference attendance. Average weekly duty hours increased by almost 5 hours
      after the implementation of the 2011 duty-hour regulations.

PMID- 25595860
TI  - Evaluation of prostaglandin E2 and E-series prostaglandin receptor in patients
      with interstitial cystitis.
AB  - PURPOSE: We evaluated PGE2 and EP receptor in patients with interstitial
      cystitis. MATERIALS AND METHODS: Enrolled in the study were 20 female patients
      with interstitial cystitis (11 with and 9 without Hunner lesions), 9 female
      controls with another urological disease who needed a cystoscopic procedure and
      10 normal volunteers. In all participants we determined O'Leary-Sant symptom and
      problem scores, and obtained voluntary urine specimens for PGE2 analysis. Using
      anesthesia the bladder was distended by saline in stepwise fashion from 100 ml to
      maximum capacity in patients with interstitial cystitis. Each time the infused
      saline was retrieved for PGE2 analysis. We also measured PGE2 and the expression
      of EP receptor mRNA in bladder biopsy tissue in patients with interstitial
      cystitis. RESULTS: Symptom and problem indexes in patients with interstitial
      cystitis and Hunner lesions were significantly higher than in patients with
      interstitial cystitis without Hunner lesions. Urinary PGE2 in patients with
      interstitial cystitis and Hunner lesions was significantly higher than in
      patients with interstitial cystitis without lesions, controls and normal
      volunteers. PGE2 in retrieved saline in patients with interstitial cystitis and
      Hunner lesions increased depending on infusion volume but not in patients with
      interstitial cystitis without lesions. PGE2 content in bladder biopsy tissue was
      significantly higher in patients with interstitial cystitis and Hunner lesions
      than in controls. In patients with interstitial cystitis and Hunner lesions the
      expression of EP1 and EP2 mRNA was significantly higher than in controls.
      CONCLUSIONS: Our study showed increased PGE2 production and mRNA expression of
      EP1 and EP2 receptors in the bladder in patients with interstitial cystitis and
      Hunner lesions. Further studies are warranted to explore the pathophysiological
      and therapeutic implications.

PMID- 25595861
TI  - Impact on Pregnancy of Gross and Microscopic Vasal Fluid during Vasectomy
      Reversal.
AB  - PURPOSE: We compared fertility outcomes with gross and microscopic fluid findings
      at vasectomy reversal at a high volume vasectomy reversal center. MATERIALS AND
      METHODS: A retrospective study of a prospective database was performed. All
      vasectomy reversals were performed by a single surgeon (EFF) between 1978 and
      2011. The clinical pregnancy rate was self-reported or determined via patient
      mailers. Patient and operative findings were determined through database review.
      We classified vasal fluid as opalescent, creamy, pasty or clear. Intraoperative
      light microscopy was used to determine if sperm or sperm parts were present and
      if they were motile. Multivariate analysis was performed evaluating patient age,
      partner age, years after vasectomy, type of surgery, and gross and microscopic
      fluid analysis. RESULTS: A total of 2,947 microsurgical vasectomy reversals were
      reviewed after we excluded reversals performed for post-vasectomy pain. We
      determined the pregnancy status of 902 (31%) cases. On univariate analysis with
      respect to pregnancy the presence of motile sperm at vasovasostomy neared
      statistical significance (p=0.075) and there was no difference between bilateral
      vs unilateral motile sperm. Gross fluid appearance was not statistically
      significant but we found the order of pregnancy success to be opalescent, creamy,
      clear then pasty fluid. On multivariate analysis only female partner age and
      sperm heads only or no sperm seen on light microscopy had statistical
      significance (p <0.05). CONCLUSIONS: The presence of motile sperm at vasectomy
      reversal approaches statistical significance on univariate analysis as a factor
      that affects clinical pregnancy rates. On multivariate analysis female partner
      age and microscopic findings of sperm heads only or no sperm are inversely
      related to pregnancy rates. These data will help counsel couples after vasectomy
      reversal and reinforce the importance of female partner age.

PMID- 25595866
TI  - Effect of display monitor devices on intra-oral radiographic caries diagnosis.
AB  - OBJECTIVES: Recent developments in digital computer technology have enabled
      radiological diagnosis to be performed using a monitor screen. In medical
      radiography, the importance of monitors has been shown in many diseases. Digital
      imaging and communication in medicine (DICOM)-compatible monitors are widely
      used. However, the effect of monitors on the diagnosis of oral disease has not
      yet been clarified and remains controversial. The aims of this study are to
      compare the caries diagnostic ability between DICOM monitors and other monitors
      and to examine if monitor capability affects the diagnosis. MATERIALS AND
      METHODS: One hundred proximal surfaces of 50 extracted human upper premolar teeth
      were used as specimens. Intra-oral radiographs of all specimens were taken
      digitally. Three types of monitors were compared in terms of caries diagnostic
      ability: a DICOM standard-compatible monitor, a standardized personal computer
      (PC) monitor, and a tablet PC. Six oral radiologists diagnosed each radiograph
      independently. Areas under the receiver operating characteristic (ROC) curve were
      generated and compared. RESULTS: Area under the ROC curve (AUC) of the DICOM
      monitor, PC monitor, and tablet PC was 0.68147, 0.67002, and 0.60189,
      respectively. There was no significant difference between the DICOM monitor and
      the PC monitor, but the tablet PC showed significantly lower accuracy. There were
      no significant differences among the monitors for dentin caries (p > 0.05).
      CONCLUSIONS: DICOM-compatible monitors and PC monitors have similar capabilities,
      but tablet PCs showed lower diagnostic accuracy, especially for superficial
      caries. CLINICAL RELEVANCE: Appropriate monitors are needed for radiographic
      diagnosis on monitor screens.

PMID- 25595865
TI  - The impact of GSTM1/GSTT1 polymorphism for the risk of oral cancer.
AB  - OBJECTIVES: Since development of oral squamous cell cancer (OSCC) is triggered by
      various noxa, different variants of the antioxidant glutathione S-transferases
      (GSTs) can counteract toxic compounds (e.g., tobacco smoke). Because different
      polymorphisms of GST are known to have an increased sensitivity to carcinogenic
      agents, the aim of this study was to analyze whether GSTM1 or GSTT1 polymorphisms
      increase the risk for the development of OSCC. MATERIALS AND METHODS: GSTM1 and
      GSTT1 polymorphism was examined in healthy volunteers (n = 93) and in patients
      with OSCC (n = 100) by PCR after brush biopsy of oral mucosa. Odds ratio (OR) was
      calculated to evaluate the risk of oral cancer development. RESULTS: GSTM1 and
      GSTT1 deletion was found in 57% (53/93) and 18% (17/93), respectively, in healthy
      patients, while the OSCC group showed 57% (57/100) for GSTM1 deletion and 22%
      (22/100) with a deletion of GSTT1. Odds ratio for GSTM1 polymorphism was 1.00 and
      for GSTT1 1.26. Comparing smokers and nonsmokers with GSTM1 deletion
      polymorphism, OR was 4.35, while smokers without GSTM1 deletion showed an OR of
      1.45. Adapting these data to the smoking habits of the general population in
      Germany, the OR was 9.25 for smokers with a GSTM1 deletion and OR 6.68 for
      smokers without a GSTM1 deletion. In smokers with GSTT1 deletion polymorphism, OR
      was 1.6 (adapted to the smoking habits of the general population: OR 6.16) and
      3.16 (OR 8.56) in smokers without deletion in GSTT1 gene. CONCLUSIONS: Analysis
      of GST-M1 polymorphism in smokers could help to identify patients with a higher
      risk for the development of oral cancer. CLINICAL RELEVANCE: Early detection of
      OSCC due to a close meshed monitoring program for patients with GST-M1
      polymorphism could help to improve the patient outcome. For polymorphism
      investigations, the oral brush biopsy is a sufficient method to gain DNA
      material.

PMID- 25595867
TI  - Compound 48/80 acts as a potent mucosal adjuvant for vaccination against
      Streptococcus pneumoniae infection in young mice.
AB  - Streptococcus pneumoniae, a major respiratory pathogen, is a leading cause of
      death among children worldwide. Mucosal vaccination is a recommended method to
      prevent respiratory infection. However, development of mucosal vaccination is
      usually hindered due to the lack of safe and effective mucosal adjuvants. Mast
      cell activator compound 48/80 (C48/80) has been used as a mucosal adjuvant in
      immunization of adult mice, but its adjuvanticity is not clear in the
      immunization of young mice. In this study, the adjuvanticity of C48/80 was
      evaluated when intranasally co-administrated with a pneumococcal vaccine
      candidate strain SPY1 in a young mice model in comparison with a classical
      mucosal adjuvant cholera toxin (CT) and a relatively safe mucosal adjuvant
      Pam2CSK4. All three adjuvants enhanced antibody responses, whereas serum IgG
      titers were maintained at a stable level during the 3 months after the last
      immunization only in the SPY1+C48/80 and SPY1+CT groups. Furthermore, both the
      SPY1+CT group and the SPY1+C48/80 group induced strong Th17 immune response.
      Notably, C48/80 showed the exceptional ability to promote the clearance of nasal
      pneumococcal colonization which CT and Pam2CSK4 did not show. We found that
      C48/80's ability to induce protection against nasal pneumococcal colonization
      depended on B cells and IL-17A. Additionally, C48/80, as a mucosal adjuvant,
      showed a greater ability to protect young mice against lethal pneumococcal
      infection than CT. In comparison with CT, C48/80 also showed a favorable safety.
      These results reveal a promising perspective for using C48/80 as a mucosal
      adjuvant to improve protection against pneumococcal diseases early in life.

PMID- 25595864
TI  - Outcome of nonsurgical retreatment and endodontic microsurgery: a meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to evaluate and compare the clinical
      and radiographic outcomes of nonsurgical endodontic retreatment and endodontic
      microsurgery by a meta-analysis. MATERIALS AND METHODS: Electronic databases
      including PubMed, Embase, Medline, and The Cochrane Library were searched, and
      the references of related articles were manually searched to identify all the
      clinical studies that evaluated the clinical and radiographic outcomes after
      retreatment or microsurgery. The first and second screening processes were
      conducted by three reviewers independently. The final studies were selected after
      strict application of the inclusion and exclusion criteria. The random effects
      meta-analysis model with the DerSimonian-Laird pooling method was performed. The
      weighted pooled success rates and 95 % confidence interval estimates of the
      outcome were calculated. Additionally, the effects of the follow-up period and
      study quality were investigated by a subgroup analysis. RESULTS: Endodontic
      microsurgery and nonsurgical retreatment have stable outcomes presenting 92 and
      80 % of overall pooled success rates, respectively. The microsurgery group had a
      significantly higher success rate than the retreatment group. When the data were
      organized and analyzed according to their follow-up periods, a significantly
      higher success rate was found for the microsurgery group in the short-term follow
      up (less than 4 years), whereas no significant difference was observed in the
      long-term follow-up (more than 4 years). CONCLUSIONS: Endodontic microsurgery was
      confirmed as a reliable treatment option with favorable initial healing and a
      predictable outcome. CLINICAL RELEVANCE: Clinicians may consider the microsurgery
      as an effective way of retreatment as well as nonsurgical retreatment depending
      on the clinical situations.

PMID- 25595868
TI  - Cost-benefit comparison of two proposed overseas programs for reducing chronic
      Hepatitis B infection among refugees: is screening essential?
AB  - BACKGROUND: Refugees are at an increased risk of chronic Hepatitis B virus (HBV)
      infection because many of their countries of origin, as well as host countries,
      have intermediate-to-high prevalence rates. Refugees arriving to the US are also
      at risk of serious sequelae from chronic HBV infection because they are not
      routinely screened for the virus overseas or in domestic post-arrival exams, and
      may live in the US for years without awareness of their infection status.
      METHODS: A cohort of 26,548 refugees who arrived in Minnesota and Georgia during
      2005-2010 was evaluated to determine the prevalence of chronic HBV infection.
      This prevalence information was then used in a cost-benefit analysis comparing
      two variations of a proposed overseas program to prevent or ameliorate the
      effects of HBV infection, titled 'Screen, then vaccinate or initiate management'
      (SVIM) and 'Vaccinate only' (VO). The analyses were performed in 2013. All values
      were converted to US 2012 dollars. RESULTS: The estimated six year period
      prevalence of chronic HBV infection was 6.8% in the overall refugee population
      arriving to Minnesota and Georgia and 7.1% in those >=6 years of age. The SVIM
      program variation was more cost beneficial than VO. While the up-front costs of
      SVIM were higher than VO ($154,084 vs. $73,758; n=58,538 refugees), the SVIM
      proposal displayed a positive net benefit, ranging from $24 million to $130
      million after only 5 years since program initiation, depending on domestic post
      arrival screening rates in the VO proposal. CONCLUSIONS: Chronic HBV infection
      remains an important health problem in refugees resettling to the United States.
      An overseas screening policy for chronic HBV infection is more cost-beneficial
      than a 'Vaccination only' policy. The major benefit drivers for the screening
      policy are earlier medical management of chronic HBV infection and averted lost
      societal contributions from premature death.

PMID- 25595869
TI  - Plasmid curing and the loss of grip--the 65-kb replicon of Phaeobacter inhibens
      DSM 17395 is required for biofilm formation, motility and the colonization of
      marine algae.
AB  - Surface colonization is characteristic for a broad range of marine roseobacters
      and many strains have been isolated from biofilms, microbial mats and
      dinoflagellates. Phaeobacter inhibens DSM 17395, one of the best-studied
      representatives of the Roseobacter group, is an effective colonizer of marine
      surfaces, but the genetic basis of this trait is unknown. Based on the
      composition of its 65-kb RepA-I type plasmid that contains more than 20 genes for
      polysaccharide metabolism, including a rhamnose operon, which is required for O
      antigen formation in Escherichia coli, it was hypothesized that this replicon was
      essential for surface attachment. Accordingly, a holistic approach was taken and
      the functional role of this extrachromosomal element in P. inhibens was
      investigated. Plasmid curing was performed with the homologous RepA-I replication
      system of Dinoroseobacter shibae DSM 16493(T). The Delta65-kb mutant completely
      lost its stickiness and could neither attach to artificial (glass, polystyrene)
      nor to natural surfaces (algae) and, consequently, its ability to form biofilms
      was impaired. Surprisingly, the mutant also lost the capacity for flagellar
      swimming motility required for surface colonization and the dispersal of
      biofilms. The data clearly showed that the 65-kb replicon of P. inhibens DSM
      17395 was a genuine biofilm plasmid-mediating surface attachment. Homologous
      replicons are widely distributed among Rhodobacterales thus indicating the
      general importance of extrachromosomal elements for biofilm formation.

PMID- 25595870
TI  - Revised phylogeny of Rhizobiaceae: proposal of the delineation of Pararhizobium
      gen. nov., and 13 new species combinations.
AB  - The family Rhizobiaceae accommodates the seven genera Rhizobium, Neorhizobium,
      Allorhizobium, Agrobacterium, Ensifer (syn. Sinorhizobium), Shinella and
      Ciceribacter. However, several so-called Rhizobium species do not exhibit robust
      phylogenetic positions. Rhizobium is extremely heterogeneous and is in need of
      major revision. Therefore, a phylogenetic examination of the family Rhizobiaceae
      by multilocus sequence analysis (MLSA) of four housekeeping genes among 100
      strains of the family was undertaken. Based on the results we propose the
      delineation of the new genus Pararhizobium in the Rhizobiaceae family, and 13 new
      species combinations: Agrobacterium nepotum comb. nov., Agrobacterium pusense
      comb. nov., Agrobacterium skierniewicense comb. nov., Allorhizobium vitis comb.
      nov., Allorhizobium taibaishanense comb. nov., Allorhizobium paknamense comb.
      nov., Allorhizobium oryzae comb. nov., Allorhizobium pseudoryzae comb. nov.,
      Allorhizobium borbori comb. nov., Pararhizobium giardinii comb. nov.,
      Pararhizobium capsulatum comb. nov., Pararhizobium herbae comb. nov., and
      Pararhizobium sphaerophysae comb. nov.

PMID- 25595871
TI  - An educational review of the statistical issues in analysing utility data for
      cost-utility analysis.
AB  - The aim of cost-utility analysis is to support decision making in healthcare by
      providing a standardised mechanism for comparing resource use and health outcomes
      across programmes of work. The focus of this paper is the denominator of the cost
      utility analysis, specifically the methodology and statistical challenges
      associated with calculating QALYs from patient-level data collected as part of a
      trial. We provide a brief description of the most common questionnaire used to
      calculate patient level utility scores, the EQ-5D, followed by a discussion of
      other ways to calculate patient level utility scores alongside a trial including
      other generic measures of health-related quality of life and condition- and
      population-specific questionnaires. Detail is provided on how to calculate the
      mean QALYs per patient, including discounting, adjusting for baseline differences
      in utility scores and a discussion of the implications of different methods for
      handling missing data. The methods are demonstrated using data from a trial. As
      the methods chosen can systematically change the results of the analysis, it is
      important that standardised methods such as patient-level analysis are adhered to
      as best as possible. Regardless, researchers need to ensure that they are
      sufficiently transparent about the methods they use so as to provide the best
      possible information to aid in healthcare decision making. 

PMID- 25595874
TI  - [IgG4-related disease treatment in 2014: Update and literature review].
AB  - IgG4-related disease is an inflammatory disorder characterized by a polyclonal
      lymphoplasmacytic tissue infiltrate, with numerous IgG4+ plasmocytes, evolving
      toward fibrosis. The disease is heterogeneous and affects several tissues and
      organs synchroneously or metachroneously. Both the fibrosis and the tumor forming
      characteristics of the disease can be responsible of irreversible tissue damage.
      For these reasons treatment is usually necessary. A dramatic response is usually
      observed with steroid treatment but relapses are frequent. Immunosuppressive
      agents and rituximab are used as second line treatments. We review here previous
      studies on treatment and suggest general recommendations for the treatment and
      follow up of patients with IgG4-related disease. 

PMID- 25595872
TI  - Lipid peroxidation in brain or spinal cord mitochondria after injury.
AB  - Extensive evidence has demonstrated an important role of oxygen radical formation
      (i.e., oxidative stress) as a mediator of the secondary injury process that
      occurs following primary mechanical injury to the brain or spinal cord. The
      predominant form of oxygen radical-induced oxidative damage that occurs in
      injured nervous tissue is lipid peroxidation (LP). Much of the oxidative stress
      in injured nerve cells initially begins in mitochondria via the generation of the
      reactive nitrogen species peroxynitrite (PN) which then can generate multiple
      highly reactive free radicals including nitrogen dioxide (*NO2), hydroxyl radical
      (*OH) and carbonate radical (*CO3). Each can readily induce LP within the
      phospholipid membranes of the mitochondrion leading to respiratory dysfunction,
      calcium buffering impairment, mitochondrial permeability transition and cell
      death. Validation of the role of LP in central nervous system secondary injury
      has been provided by the mitochondrial and neuroprotective effects of multiple
      antioxidant agents which are briefly reviewed. 

PMID- 25595875
TI  - [Bevacizumab: a new success in hereditary hemorrhagic telangiectasia].
AB  - INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT), is a rare, hereditary
      vascular dysplasia, characterized by recurrent epistaxis, mucocutaneous
      telangiectasias and visceral arteriovenous malformations. The vascular
      endothelial growth factor VEGF seems to play a crucial role in the pathogenesis
      of this disease. Recently bevacizumab, a humanized monoclonal VEGF inhibitor, has
      shown promise in treating patients with HHT. CASE REPORT: A 66-year-old man,
      having HHT since the age of 30 years with recurrent epistaxis related to
      telangiectasia at the nasal septum and chronic iron deficiency anemia requiring
      frequent blood transfusions with iron infusions. The assessment of his disease
      showed septal perforation, telangiectasis in the proximal jejunum and terminal
      ileum, and pulmonary arteriovenous malformations. There was no improvement,
      despite iron infusions, repeated blood transfusions and cauterization. The
      patient was treated with bevacizumab at a dose of 5mg/kg/infusion every 2 weeks
      and was given 6 cycles. Bevacizumab, was effective without side effects.
      DISCUSSION: It has been hypothesized that HHT is related to an imbalanced state
      between antiangiogenic factors and proangiogenic factors. Mutations of 3 genes
      are actually identified in HHT: ENG, ACVRL1, MADH4. The management of patients
      with HHT currently based on screening for visceral arteriovenous malformations
      and symptomatic measures are often disappointing. However, the angiogenic nature
      of this disease suggests an interesting therapy by using angiogenesis inhibitor.
      Therefore, bevacizumab was introduced as a potential therapy for HHT. Some
      clinical cases or small series report the efficacy of bevacizumab, in HHT with
      recurrent epistaxis, refractory iron deficiency anemia, gastrointestinal bleeding
      and also in liver vascular malformations with high cardiac output failure.
      CONCLUSION: The use of modulators of angiogenesis such as bevacizumab is a
      possible therapeutic target in HHT.

PMID- 25595876
TI  - [Cryopyrine-associated periodic syndrome: CAPS seen from adulthood].
AB  - Cryopyrin-associated periodic syndrome is a rare hereditary periodic fever
      syndrome for which, the genetic mechanism, mutation in the NLRP3 gene, has
      allowed to gather 3 clinical phenotypes (familial cold urticaria [FCAS], Muckle
      Wells syndrome [MWS], and chronic infantile neurological cutaneous and articular
      syndrome [CINCA]) initially described independently, and to discover the NLRP3
      inflammasome, a key receptor of the innate immunity, which regulates the
      interleukine-1beta secretion into the mononuclear cells. The clinical
      manifestation of CAPS : urticaria-like skin rash, eyes redness, myalgia and
      sensory deafness are not specific, if considered separately, and that often leads
      to a wandering diagnosis through a complex medical journey including various
      specialists. The diagnostic delay is deleterious to patients compromising their
      quality of life and exposing them to neurosensory complications and renal failure
      by secondary amyloidosis. The paediatric onset of disease, the family history,
      the trigger of symptoms by the cold, and the recognition of the skin rash as
      neutrophilic are important clues before diagnostic confirmation by genetic
      testing. Interleukine-1 blockade is the only effective treatment of CAPS symptoms
      which often may stabilize (rarely regression) the sensory involvement and in some
      cases may allow the regression of secondary amyloidosis. 

PMID- 25595877
TI  - [Diagnostic approach of recurrent fevers of unknown origin in adults].
AB  - Recurrent fever of unknown origin is probably the most difficult to diagnose
      subtype of fever of unknown origin. It represents between 18 and 42% of the cases
      in large series of patients with fever of unknown origin. The limited literature
      data do not allow one to construct a diagnostic algorithm. However, the
      diagnostic strategy is different from classic fever of unknown origin. The
      spectrum of causative disorders is different from continuous fever with less
      infections and tumors. Among systemic inflammatory diseases, adult-onset Still's
      disease is the most common cause. More than 50% of the cases remain unexplained.
      Hereditary recurrent fevers, the prototype of autoinflammatory diseases, are now
      more easily discuss in a young adult. 

PMID- 25595878
TI  - [Parapneumonic pleural effusions: Epidemiology, diagnosis, classification and
      management].
AB  - Parapneumonic pleural effusions represent the main cause of pleural infections.
      Their incidence is constantly increasing. Although by definition they are
      considered to be a "parapneumonic" phenomenon, the microbial epidemiology of
      these effusions differs from pneumonia with a higher prevalence of anaerobic
      bacteria. The first thoracentesis is the most important diagnostic stage because
      it allows for a distinction between complicated and non-complicated parapneumonic
      effusions. Only complicated parapneumonic effusions need to be drained.
      Therapeutic evacuation modalities include repeated therapeutic thoracentesis,
      chest tube drainage or thoracic surgery. The choice of the first-line evacuation
      treatment is still controversial and there are few prospective controlled
      studies. The effectiveness of fibrinolytic agents is not established except when
      they are combined with DNase. Antibiotics are mandatory; they should be initiated
      as quickly as possible and should be active against anaerobic bacteria except for
      in the context of pneumococcal infections. There are few data on the use of chest
      physiotherapy, which remains widely used. Mortality is still high and is
      influenced by underlying comorbidities. 

PMID- 25595879
TI  - [S.AGES Study. Collection and follow-up of new sleep apnea cases in patients over
      70 years of age and diagnosed in pulmonary and geriatric units].
AB  - RATIONALE: S.AGES is a prospective cohort of >70-years-old patients with
      obstructive sleep apnea syndrome having been diagnosed in a pulmonary or a
      geriatric medical unit. OBJECTIVES: The main objective of S.AGES is to get a
      description of older patients with OSAS in France. The secondary objectives will
      be to prospectively describe the management and the treatment of these patients,
      to describe their 5-years outcome as compared to younger patients in the
      literature. It will also contribute to better characterize the compliance and
      tolerance of the treatment and the incidence of comorbidities like respiratory
      diseases and cardiovascular disorders. METHODS: All consecutive >=70-years-old
      patients having received a diagnosis of OSAS (after polygraphy or
      polysomnography) will be included in the study. All patients will be followed in
      a pulmonary or a geriatric department. EXPECTED RESULTS: S.AGES should better
      characterize the OSAS in the elderly patients, the specific management of this
      disease and its related risk factors. It may also identify the 5-years mortality
      and morbidity rates in this population.

PMID- 25595880
TI  - The integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal
      inhibitory avoidance memory.
AB  - The purpose of this review is to summarize the present knowledge on the interplay
      among the cholinergic system, Extracellular signal-Regulated Kinase (ERK) and
      Mammalian Target of Rapamycin (mTOR) pathways in the development of short and
      long term memories during the acquisition and recall of the step-down inhibitory
      avoidance in the hippocampus. The step-down inhibitory avoidance is a form of
      associative learning that is acquired in a relatively simple one-trial test
      through several sensorial inputs. Inhibitory avoidance depends on the integrated
      activity of hippocampal CA1 and other brain areas. Recall can be performed at
      different times after acquisition, thus allowing for the study of both short and
      long term memory. Among the many neurotransmitter systems involved, the
      cholinergic neurons that originate in the basal forebrain and project to the
      hippocampus are of crucial importance in inhibitory avoidance processes.
      Acetylcholine released from cholinergic fibers during acquisition and/or recall
      of behavioural tasks activates muscarinic and nicotinic acetylcholine receptors
      and brings about a long-lasting potentiation of the postsynaptic membrane
      followed by downstream activation of intracellular pathway (ERK, among others)
      that create conditions favourable for neuronal plasticity. ERK appears to be
      salient not only in long term memory, but also in the molecular mechanisms
      underlying short term memory formation in the hippocampus. Since ERK can function
      as a biochemical coincidence detector in response to extracellular signals in
      neurons, the activation of ERK-dependent downstream effectors is determined, in
      part, by the duration of ERK phosphorylation itself. Long term memories require
      protein synthesis, that in the synapto-dendritic compartment represents a direct
      mechanism that can produce rapid changes in protein content in response to
      synaptic activity. mTOR in the brain regulates protein translation in response to
      neuronal activity, thereby modulating synaptic plasticity and long term memory
      formation. Some studies demonstrate a complex interplay among the cholinergic
      system, ERK and mTOR. It has been shown that co-activation of muscarinic
      acetylcholine receptors and beta-adrenergic receptors facilitates the conversion
      of short term to long term synaptic plasticity through an ERK- and mTOR-dependent
      mechanism which requires translation initiation. It seems therefore that the
      complex interplay among the cholinergic system, ERK and mTOR is crucial in the
      development of new inhibitory avoidance memories in the hippocampus. 

PMID- 25595881
TI  - Clinical use of Haemate(r) P in von Willebrand disease: a 25-year retrospective
      observational study.
AB  - INTRODUCTION: von Willebrand disease (VWD) is caused by dysfunction or diminished
      levels of von Willebrand factor (VWF). VWF-containing plasma concentrates are
      used for treatment of patients with VWD for whom desmopressin treatment is
      insufficient or contraindicated. A single-centre, retrospective observational
      study over a period of up to 25 years was conducted to evaluate the effectiveness
      and safety profile of Haemate((r)) P (CSL Behring, Marburg, Germany), a plasma
      derived, purified, pasteurised and lyophilised VWF-containing factor VIII (FVIII)
      concentrate. MATERIALS AND METHODS: The study included 71 patients who had been
      treated with Haemate((r)) P over a period of > 5 years. RESULTS: A total of 663
      treatments with individual laboratory evaluations were recorded. Two patients had
      both mild type 1 VWD and haemophilia A (HA), three had HA only, 39 had type 1
      VWD, 16 had type 2 VWD, nine had type 3 VWD, one had acquired VWD and one had
      uncategorised VWD. Haemate((r)) P treatment indications included bleeding events
      (37 patients) and surgical interventions (70 patients). Thirteen patients
      received Haemate((r)) P as long-term prophylaxis (n = 3), as part of
      rehabilitation treatment (n = 5), or in context of recovery measurements (n = 5).
      Treatment with Haemate((r)) P was generally well tolerated; only one
      thromboembolic event occurred. In cases of bleeding events, Haemate((r)) P was
      haemostatically effective in all patients. Furthermore, during operations where
      Haemate((r)) P was administered, >90% incurred no complications. CONCLUSION: In
      this retrospective observational study, Haemate((r)) P was shown to be effective
      and safe for the treatment of VWD in adult patients.

PMID- 25595882
TI  - Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit
      hepatosteatosis.
AB  - BACKGROUND & AIMS: Obesity and associated metabolic syndrome have quickly become
      a pandemic and a major detriment to global human health. The presence of non
      alcoholic fatty liver disease (NAFLD; hepatosteatosis) in obesity has been linked
      to the worsening of the metabolic syndrome, including the development of insulin
      resistance and cardiovascular disease. Currently, there are few options to treat
      NAFLD, including life style changes and insulin sensitizers. Recent evidence
      suggests that the cannabinoids Delta(9)-tetrahydrocannabivarin (THCV) and
      cannabidiol (CBD) improve insulin sensitivity; we aimed at studying their effects
      on lipid levels. METHODS: The effects of THCV and CBD on lipid levels were
      examined in a variety of in vitro and in vivo systems, with special emphasis on
      models of hepatosteatosis. Transcriptional, post-translational and metabolomic
      changes were assayed. RESULTS: THCV and CBD directly reduce accumulated lipid
      levels in vitro in a hepatosteatosis model and adipocytes. Nuclear magnetic
      resonance- (NMR) based metabolomics confirmed these results and further
      identified specific metabolic changes in THCV and CBD-treated hepatocytes.
      Treatment also induced post-translational changes in a variety of proteins such
      as CREB, PRAS40, AMPKa2 and several STATs indicating increased lipid metabolism
      and, possibly, mitochondrial activity. These results are supported by in vivo
      data from zebrafish and obese mice indicating that these cannabinoids are able to
      increase yolk lipid mobilization and inhibit the development of hepatosteatosis
      respectively. CONCLUSIONS: Our results suggest that THCV and CBD might be used as
      new therapeutic agents for the pharmacological treatment of obesity- and
      metabolic syndrome-related NAFLD/hepatosteatosis.

PMID- 25595883
TI  - Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and
      modification with current antiviral therapy.
AB  - In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing
      hepatitis B virus (HBV)-associated liver disease, including hepatocellular
      carcinoma (HCC). Recently published studies show that in CHB patients treated
      with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir
      or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic
      patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies
      including matched untreated controls, current NA therapy consistently resulted in
      a significantly lower HCC incidence in patients with cirrhosis, amounting to an
      overall HCC risk reduction of ~30%; in non-cirrhotic patients, HCC risk reduction
      was overall ~80%, but this was only observed in some studies. For patients of
      Caucasian origin, no appropriate comparative studies are available to date to
      evaluate the impact of NA treatment on HCC. Achievement of a virologic response
      under current NA therapy was associated with a lower HCC risk in Asian, but not
      Caucasian studies. Studies comparing entecavir or tenofovir with older NAs
      generally found no difference in HCC risk reduction between agents, except for
      one study which used no rescue therapy in patients developing lamivudine
      resistance. Overall, these data indicate that with the current, potent NAs, HCC
      risk can be reduced but not eliminated, probably due to risk factors that are not
      amenable to change by antiviral therapy, or events that may have taken place
      before treatment initiation. Validated pre- and on-therapy HCC risk calculators
      that inform the best practice for HCC surveillance and facilitate patient
      counseling would be of great practical value. 

PMID- 25595884
TI  - Hepatic p38alpha regulates gluconeogenesis by suppressing AMPK.
AB  - BACKGROUND & AIMS: It is proposed that p38 is involved in gluconeogenesis,
      however, the genetic evidence is lacking and precise mechanisms remain poorly
      understood. We sought to delineate the role of hepatic p38alpha in
      gluconeogenesis during fasting by applying a loss-of-function genetic approach.
      METHODS: We examined fasting glucose levels, performed pyruvate tolerance test,
      imaged G6Pase promoter activity, as well as determined the expression of
      gluconeogenic genes in mice with a targeted deletion of p38alpha in liver.
      Results were confirmed both in vivo and in vitro by using an adenoviral dominant
      negative form of p38alpha (p38alpha-AF) and the constitutively active mitogen
      activated protein kinase 6, respectively. Adenoviral dominant-negative form of
      AMP-activated protein kinase alpha (DN-AMPKalpha) was employed to test our
      proposed model. RESULTS: Mice lacking hepatic p38alpha exhibited reduced fasting
      glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of
      p38alpha did not result in an alteration in CREB phosphorylation, but led to an
      increase in AMPKalpha phosphorylation. Adenoviral DN-AMPKalpha could abolish the
      effect of p38alpha-AF on gluconeogenesis. Knockdown of up-steam transforming
      growth factor beta-activated kinase 1 decreased the AMPKalpha phosphorylation
      induced by p38alpha-AF, suggesting a negative feedback loop. Consistently,
      inverse correlations between p38 and AMPKalpha phosphorylation were observed
      during fasting and in diabetic mouse models. Importantly, adenoviral p38alpha-AF
      treatment ameliorated hyperglycemia in diabetic mice. CONCLUSIONS: Our study
      provides evidence that hepatic p38alpha functions as a negative regulator of AMPK
      signaling in maintaining gluconeogenesis, dysregulation of this regulatory
      network contributes to unrestrained gluconeogenesis in diabetes, and hepatic
      p38alpha could be a drug target for hyperglycemia.

PMID- 25595885
TI  - Loss of ileum decreases serum fibroblast growth factor 19 in relation to liver
      inflammation and fibrosis in pediatric onset intestinal failure.
AB  - BACKGROUND & AIMS: The pathogenesis of intestinal failure (IF) associated liver
      disease (IFALD) is uncertain, we therefore investigated the role of FGF19 and pro
      inflammatory cytokines has on this disease state. METHODS: Serum FGF19, IL-6 and,
      TNF-alpha were measured in 52 IF patients at median age 6.0 years (IQR 2.2-13)
      after 10 months (4.1-39) on parenteral nutrition (PN). Thirty-nine patients
      underwent liver biopsies. RESULTS: In IF patients, FGF19 concentrations were
      lower and those of IL-6 and TNF-alpha higher compared to healthy matched controls
      (p ? 0.001 for all). FGF19 concentrations were further decreased in patients
      without a remaining ileum [37 pg/ml (IQR 30-68) vs. 74 (35-135) p=0.028], and
      correlated with remaining ileum length (r = 0.333, p = 0.018) and markers of
      cholesterol synthesis (r = -0.552 to -0.643, p < 0.001). Patients with
      histological portal inflammation [30 pg/ml (28-45) vs. 48 (33-100), p = 0.019] or
      fibrosis [35 pg/ml (30-66) vs. 99 (38-163), p = 0.013] had lower serum FGF19
      concentrations than others. FGF19 negatively correlated with portal inflammation
      grade (r = -0.442, p = 0.005), serum TNF-alpha (r = -0.318, p = 0.025), METAVIR
      fibrosis stage (r = -0.441, p = 0.005) and APRI (r = -0.328, p = 0.028). IL-6 was
      higher during PN [6 pg/ml (2-31)] than after weaning off PN [2 pg/ml (1-5), p =
      0.009], correlated weakly with cholestasis grade (r = 0.328, p = 0.044), and
      tended to associate with histological cholestasis [n = 5, 5 pg/ml (5-267) vs.
      n=34, 2 pg/ml (1-7), p = 0.058]. CONCLUSIONS: In pediatric onset of IF, total or
      partial loss of ileum decreases serum FGF19 concentration corresponding to
      hepatic inflammation and fibrosis, along with increased cholesterol synthesis. In
      contrast, serum IL-6 increases during PN and may associate with concurrent
      cholestasis. These data suggests that FGF19 may contribute to the pathogenesis of
      IFALD.

PMID- 25595886
TI  - Thyroxine softgel capsule in patients with gastric-related T4 malabsorption.
AB  - The key role of an intact gastric acid secretion for subsequent intestinal T4
      absorption is supported by an increased requirement of thyroxine in patients with
      gastric disorders. A better pH-related dissolution profile has been described in
      vitro for softgel T4 preparation than for T4 tablets. Our study was aimed at
      comparing softgel and tablet T4 requirements in patients with gastric disorders.
      A total of 37 patients with gastric-related T4 malabsorption were enrolled, but
      only 31 (28F/3M; median age = 50 years; median T4 dose = 2.04 MUg/kg/day)
      completed the study. All patients were in long-lasting treatment (>2 years) with
      the same dose of T4 tablets when treatment was switched to a lower dose of
      softgel T4 capsules (-17 %; p = 0.0002). Assessment of serum FT4 and TSH was
      carried out at baseline and after 3, 6, 12, and 18 months after the treatment
      switch. In more than 2/3 of patients (good-responders n = 21), despite the
      reduced dose of T4, median TSH values were similar at each time point (p =
      0.3934) with no change in FT4 levels. In the remaining patients (poor-responders
      n = 10), TSH levels were significantly higher at each time point than at baseline
      (p < 0.0001). To note, in five of them intestinal comorbidity was subsequently
      detected. Comorbidity associated with poor-responders status was the only
      significant predictor in multivariate analysis (OR = 11.333). Doses of softgel T4
      capsules lower than T4 tablet preparation are required to maintain the
      therapeutic goal in 2/3 of patients with impaired gastric acid secretion.

PMID- 25595887
TI  - Association between allergic sensitization and exhaled nitric oxide in children
      in the School Inner-City Asthma Study.

PMID- 25595888
TI  - Oral immunotherapy in cow's milk allergic patients: course and long-term outcome
      according to asthma status.
AB  - BACKGROUND: Patients with asthma and food allergy comprise a high-risk group for
      life-threatening reactions at accidental exposure. OBJECTIVE: To examine the
      course and long-term outcome of patients with asthma completing milk oral
      immunotherapy. METHODS: Children at least 6 years old with (n = 101) and without
      (n = 93) asthma and IgE-mediated cow's milk allergy, undergoing milk oral
      immunotherapy from April 2010 to December 2011, were compared. Milk dose
      escalations were performed until patients reached full (>7.2 g of milk protein)
      or partial desensitization. Skin prick tests in all patients and spirometry in
      those with asthma were performed. Patients who completed treatment were followed
      for longer than 6 months. RESULTS: Before immunotherapy, patients with asthma,
      regardless of severity, had more anaphylactic reactions (84.2% vs 64.5%, P =
      .003), emergency department visits (68.3% vs 51.6%, P = .02), and hospital
      admissions (32.7% vs 18.3%, P = .03) compared with patients without asthma.
      Patients with asthma, regardless of severity, had more reactions and injectable
      epinephrine use during induction (P = .004) and home treatments (P = .007) of
      immunotherapy. Moderate to severe asthma was associated with a lower likelihood
      of reaching full desensitization (51.5% vs 68.8%, P = .019), but most patients
      with asthma (87 of 101, 86.1%), regardless of severity, reached a dose likely to
      protect them against accidental exposure. Most patients with asthma continued to
      consume milk protein freely after completion of immunotherapy. Although adverse
      reactions were still observed, severe reactions appeared to subside with time.
      CONCLUSION: Patients with asthma are at risk for more severe reactions and are
      less likely to reach full desensitization during food oral immunotherapy.
      However, most reach limited daily consumption and most who achieve full
      desensitization continue to consume milk protein freely after treatment.

PMID- 25595889
TI  - Intratumoral diversity of telomere length in individual neuroblastoma tumors.
AB  - The purpose of the work was to investigate telomere length (TL) and mechanisms
      involved in TL maintenance in individual neuroblastoma (NB) tumors. Primary NB
      tumors from 102 patients, ninety Italian and twelve Spanish, diagnosed from 2000
      to 2008 were studied. TL was investigated by quantitative fluorescence in situ
      hybridization (IQ-FISH) that allows to analyze individual cells in paraffin
      embedded tissues. Fluorescence intensity of chromosome 2 centromere was used as
      internal control to normalize TL values to ploidy. Human telomerase reverse
      transcriptase (hTERT) expression was detected by immunofluorescence in 99/102 NB
      specimens.The main findings are the following: 1) two intratumoral subpopulations
      of cancer cells displaying telomeres of different length were identified in
      32/102 tumors belonging to all stages. 2) hTERT expression was detected in 99/102
      tumors, of which 31 displayed high expression and 68 low expression. Alternative
      lengthening of telomeres (ALT)-mechanism was present in 60/102 tumors, 20 of
      which showed high hTERT expression. Neither ALT-mechanism nor hTERT expression
      correlated with heterogeneous TL. 3) High hTERT expression and ALT positivity
      were associated with significantly reduced Overall Survival. 4) High hTERT
      expression predicted relapse irrespective of patient age. Intratumoral diversity
      in TL represents a novel feature in NB.In conclusion, diversity of TL in
      individual NB tumors was strongly associated with disease progression and death,
      suggesting that these findings are of translational relevance. The combination of
      high hTERT expression and ALT positivity may represent a novel biomarker of poor
      prognosis that deserves further investigation. 

PMID- 25595890
TI  - Mutational spectrum of adult T-ALL.
AB  - Novel target discovery is warranted to improve treatment in adult T-cell acute
      lymphoblastic leukemia (T-ALL) patients. We provide a comprehensive study on
      mutations to enhance the understanding of therapeutic targets and studied 81
      adult T-ALL patients. NOTCH1 exhibitedthe highest mutation rate (53%). Mutation
      frequencies of FBXW7 (10%), WT1 (10%), JAK3 (12%), PHF6 (11%), and BCL11B (10%)
      were in line with previous reports. We identified recurrent alterations in
      transcription factors DNM2, and RELN, the WNT pathway associated cadherin FAT1,
      and in epigenetic regulators (MLL2, EZH2). Interestingly, we discovered novel
      recurrent mutations in the DNA repair complex member HERC1, in NOTCH2, and in the
      splicing factor ZRSR2. A frequently affected pathway was the JAK/STAT pathway
      (18%) and a significant proportion of T-ALL patients harboured mutations in
      epigenetic regulators (33%), both predominantly found in the unfavourable
      subgroup of early T-ALL. Importantly, adult T-ALL patients not only showed a
      highly heterogeneous mutational spectrum, but also variable subclonal allele
      frequencies implicated in therapy resistance and evolution of relapse. In
      conclusion, we provide novel insights in genetic alterations of signalling
      pathways (e.g. druggable by gamma-secretase inhibitors, JAK inhibitors or EZH2
      inhibitors), present in over 80% of all adult T-ALL patients, that could guide
      novel therapeutic approaches. 

PMID- 25595891
TI  - Amyloid accumulation is a late event in sporadic Alzheimer's disease-like
      pathology in nontransgenic rats.
AB  - The amyloid cascade hypothesis posits that deposition of the amyloid beta (Abeta)
      peptide in the brain is a key event in the initiation of Alzheimer's disease
      (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is
      the cause of sporadic AD, which leads to cognitive decline. Here, using
      accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of
      Abeta is a later event in AD-like pathology. We showed that an age-dependent
      increase in the levels of Abeta1-42 and extracellular Abeta deposits in the brain
      of OXYS rats occur later than do synaptic losses, neuronal cell death,
      mitochondrial structural abnormalities, and hyperphosphorylation of the tau
      protein. We identified the variants of the genes that are strongly associated
      with the risk of either late-onset or early-onset AD, including App, Apoe4,
      Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs
      were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS
      rats may be a model of sporadic AD. It is possible that multiple age-associated
      pathological processes may precede the toxic amyloid accumulation, which in turn
      triggers the final stage of the sporadic form of AD and becomes a hallmark event
      of the disease.

PMID- 25595892
TI  - Somatic MED12 mutations are associated with poor prognosis markers in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. We
      performed systematic database search and identified highly specific MED12
      mutations in CLL patients. To study this further, we collected three independent
      sample series comprising over 700 CLL samples and screened MED12 exons 1 and 2 by
      direct sequencing. Mutations were identified at significant frequency in all
      three series with a combined mutation frequency of 5.2% (37/709). Positive
      mutation status was found to be associated with unmutated IGHV and ZAP70
      expression, which are well-known poor prognosis markers in CLL. Our results
      recognize CLL as the first extrauterine cancer type where 5'terminus of MED12 is
      mutated at significant frequency. Functional analyses have shown that these
      mutations lead to dissociation of Cyclin C-CDK8/19 from the core Mediator and to
      the loss of Mediator-associated CDK kinase activity. Additional studies on the
      role of MED12 mutation status as a putative prognostic factor as well as
      mutations' exact tumorigenic mechanism in CLL are warranted. 

PMID- 25595893
TI  - Identification of PAM4 (clivatuzumab)-reactive epitope on MUC5AC: a promising
      biomarker and therapeutic target for pancreatic cancer.
AB  - PAM4 is a monoclonal antibody showing high specificity for pancreatic ductal
      adenocarcinoma (PDAC). Humanized PAM4 labeled with 90Y in combination with low
      dose gemcitabine has shown promising therapeutic activity, and is being evaluated
      in a phase III clinical trial. Prior efforts have suggested that PAM4 potentially
      reacts with MUC5AC, a secretory mucin expressed de novo in early pancreatic
      neoplasia and retained throughout disease progression. In present study, we
      provide further evidence validating MUC5AC as the PAM4 antigen, and locate PAM4
      reactive epitope within the N-terminal cysteine-rich subdomain 2 (Cys2), thus
      differentiating PAM4 from most anti-MUC5AC antibodies known to-date.
      Specifically, we show (i) PAM4-antigen and MUC5AC were co-localized in multiple
      human cancer cell lines, including Capan-1, BxPC-3, and CFPAC-1; (ii) MUC5AC
      specific siRNA prominently reduced the expression of both MUC5AC and PAM4-antigen
      in CFPAC-1 cells; (iii) PAM4 preferentially binds to the void-volume fractions
      from Sepharose-CL2B chromatography of Capan-1 culture supernatants, which were
      revealed by Western blot to display the ladder pattern characteristic of
      oligomeric MUC5AC; and (iv) the N-terminal Cys2 within several recombinant MUC5AC
      fragments is essential for binding to PAM4. These findings shed light on the
      mechanism of PAM4-based diagnosis and treatment for pancreatic cancer, and guide
      further exploration of its clinical utility. 

PMID- 25595894
TI  - PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent
      genes involved in EMT and cell migration.
AB  - PATZ1, a POZ-Zinc finger protein, is emerging as an important regulator of
      development and cancer, but its cancer-related function as oncogene or tumor
      suppressor is still debated. Here, we investigated its possible role in thyroid
      carcinogenesis. We demonstrated PATZ1 is down-regulated in thyroid carcinomas
      compared to normal thyroid tissues, with an inverse correlation to the degree of
      cell differentiation. In fact, PATZ1 expression was significantly further down
      regulated in poorly differentiated and anaplastic thyroid cancers compared to the
      papillary histotype, and it resulted increasingly delocalized from the nucleus to
      the cytoplasm proceeding from differentiated to undifferentiated thyroid
      carcinomas. Restoration of PATZ1 expression in three thyroid cancer-derived cell
      lines, all characterized by fully dedifferentiated cells, significantly inhibited
      their malignant behaviors, including in vitro proliferation, anchorage
      independent growth, migration and invasion, as well as in vivo tumor growth.
      Consistent with recent studies showing a role for PATZ1 in the p53 pathway, we
      showed that ectopic expression of PATZ1 in thyroid cancer cells activates p53
      dependent pathways opposing epithelial-mesenchymal transition and cell migration
      to prevent invasiveness. These results provide insights into a potential tumor
      suppressor role of PATZ1 in thyroid cancer progression, and thus may have
      potential clinical relevance for the prognosis and therapy of thyroid cancer. 

PMID- 25595895
TI  - CBX7 and HMGA1b proteins act in opposite way on the regulation of the SPP1 gene
      expression.
AB  - Several recent studies have reported the Polycomb Repressive Complex 1 member
      CBX7 as a tumor-suppressor gene whose expression progressively decreases in
      different human carcinomas in relation with tumor grade, malignant stage and poor
      prognosis. We have previously demonstrated that CBX7 is able to inhibit the
      expression of the SPP1 gene, encoding the chemokine osteopontin that is over
      expressed in cancer and has a critical role in cancer progression. Here, we have
      analyzed the mechanism by which CBX7 regulates the SPP1 gene expression. We show
      that the SPP1 transcriptional regulation mechanism involves the CBX7-interacting
      protein HMGA1b, that acts as a positive regulator of the SPP1 gene. In fact, we
      demonstrate that, in contrast with the transcriptional activity of CBX7, HMGA1b
      is able to increase the SPP1 expression by inducing the activity of its promoter.
      Moreover, we show that CBX7 interferes with HMGA1b on the SPP1 promoter and
      counteracts the positive transcriptional activity of HMGA1b on the SPP1
      expression. Furthermore, since we found that also the NF-kappaB complex resulted
      involved in the modulation of the SPP1 expression in thyroid cells, we suppose
      that CBX7/HMGA1b/NF-kappaB could take part in the same transcriptional mechanism
      that finally leads to the regulation of the SPP1 gene expression. Taken together,
      our data show the important role played by CBX7 in the negative regulation of the
      SPP1 gene expression, thus contributing to prevent the acquisition of a malignant
      phenotype. 

PMID- 25595896
TI  - Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1,
      independent of sonic hedgehog level.
AB  - Glioblastoma Multiforme (GBM), the most common and lethal adult primary tumor of
      the brain, showed a link between Sonic Hedgehog (SHH) pathway in the resistance
      to temozolomide (TMZ). PTCH1, the SHH receptor, can tonically represses signaling
      by endocytosis. We asked how the decrease in PTCH1 in GBM cells could lead to TMZ
      resistance. TMZ resistant GBM cells have increased PTCH1 mRNA and reduced
      protein. Knockdown of Dicer, a Type III RNAase, indicated that miRNAs can explain
      the decreased PTCH1 in TMZ resistant cells. Computational studies, real-time PCR,
      reporter gene studies, western blots, target protector oligos and ectopic
      expression identified miR-9 as the target of PTCH1 in resistant GBM cells with
      concomitant activation of SHH signaling. MiR-9 mediated increases in the drug
      efflux transporters, MDR1 and ABCG2. MiR-9 was increased in the tissues from GBM
      patients and in an early passage GBM cell line from a patient with recurrent GBM
      but not from a naive patient. Pharmacological inhibition of SHH signaling
      sensitized the GBM cells to TMZ. Taken together, miR-9 targets PTCH1 in GBM cells
      by a SHH-independent method in GBM cells for TMZ resistance. The identified
      pathways could lead to new strategies to target GBM with combinations of drugs. 

PMID- 25595897
TI  - Targeting VEGFR1- and VEGFR2-expressing non-tumor cells is essential for
      esophageal cancer therapy.
AB  - Increasing appreciation of tumor heterogeneity and the tumor-host interaction has
      stimulated interest in developing novel therapies that target both tumor cells
      and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute
      important components of the tumor microenvironment. In this study, we aim to
      investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells,
      including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2
      targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can
      significantly attenuate VEGF-induced Src and Erk signaling, as well as the
      proliferation and migration of VEGFR1+ and VEGFR2+ bone marrow cells and their
      pro-invasive effect on cancer cells. Importantly, our in vivo data show for the
      first time that systemic blockade of VEGFR1+ or VEGFR2+ non-tumor cells with
      neutralizing antibodies is sufficient to significantly suppress esophageal tumor
      growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray
      study of human EC clinical specimens showed the clinicopathological significance
      of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may
      be particularly beneficial for patients with aggressive EC. In conclusion, this
      study demonstrates the important contributions of VEGFR1+ and VEGFR2+ non-tumor
      cells in esophageal cancer progression, and substantiates the validity of these
      receptors as therapeutic targets for this deadly disease.

PMID- 25595898
TI  - The T-box transcription factor, TBX3, is a key substrate of AKT3 in
      melanomagenesis.
AB  - The AKT3 signalling pathway plays a critical role in melanoma formation and
      invasion and components of this signalling cascade are therefore attractive
      targets for the treatment of malignant melanoma. Recent evidence show that the
      embryonically important TBX3 transcription factor is upregulated in a subset of
      melanomas and plays a key role in promoting melanoma formation and invasion, in
      part by repressing the cell adhesion molecule E-cadherin. We have identified TBX3
      as a key substrate of AKT3 in melanomagenesis. Briefly, using site-directed
      mutagenesis and in vitro kinase assays, we have identified the AKT3 target site
      at serine residue 720 in the TBX3 protein and show that this site is
      phosphorylated in vivo. Importantly, we show by western blotting,
      immunofluorescence, reporter, migration and invasion assays that the
      phosphorylation at S720 promotes TBX3 protein stability, nuclear localization,
      transcriptional repression of E-cadherin, and its role in cell migration and
      invasion. Our results identify a novel signalling and transcriptional network
      linking AKT3, TBX3 and E-cadherin during melanoma migration and invasion and
      reveals TBX3 as a potential target for anti-metastatic therapeutics. 

PMID- 25595899
TI  - Epidermal growth factor-induced cyclooxygenase-2 enhances head and neck squamous
      cell carcinoma metastasis through fibronectin up-regulation.
AB  - Epidermal growth factor receptor (EGFR) activation is a major cause of metastasis
      in many cancers, such as head and neck squamous cell carcinoma (HNSCC). However,
      whether the induction of cyclooxygenase-2 (COX-2) mediates EGF-enhanced HNSCC
      metastasis remains unclear. Interestingly, we found that EGF induced COX-2
      expression mainly in HNSCC. The tumor cell transformation induced by EGF was
      repressed by COX-2 knockdown, and this repression was reversed by simultaneously
      treating the cells with EGF and prostaglandin E2 (PGE2). The down-regulation of
      COX-2 expression or inhibition of COX-2 activity significantly blocked EGF
      enhancement of cell migration and invasion, but the addition of PGE2 compensated
      for this inhibitory effect in COX-2-knockdown cells. COX-2 depletion inhibited
      EGF-induced matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, and
      fibronectin expression and Rac1/cdc42 activation. The inhibitory effect of COX-2
      depletion on MMPs and the fibronectin/Rac1/cdc42 axis were reversed by co
      treatment with PGE2. Furthermore, depletion of fibronectin impeded the COX-2
      enhanced binding of HNSCC cells to endothelial cells and tumor cells metastatic
      seeding of the lungs. These results demonstrate that EGF-induced COX-2 expression
      enhances HNSCC metastasis via activation of the fibronectin signaling pathway.
      The inhibition of COX-2 expression and activation may be a potential strategy for
      the treatment of EGFR-mediated HNSCC metastasis.

PMID- 25595900
TI  - Down-regulation of G9a triggers DNA damage response and inhibits colorectal
      cancer cells proliferation.
AB  - G9a, a histone methyltransferase, is aberrantly expressed in some human tumor
      types. By comparing 182 paired colorectal cancer and peritumoral tissues, we
      found that G9a was highly expressed in colorectal cancer (CRC). Overexpression of
      G9a promoted CRC cells proliferation and colony formation, whereas knockdown of
      G9a inhibited CRC cells proliferation. Depletion of G9a increased the rate of
      chromosome aberration, induced DNA double strand breaks and CRC cells senescence.
      G9a inhibition synergistically increased gammaH2AX expression induced by
      topoisomerase I inhibitors and ultimately led to CRC cell death. The findings
      that down-regulation of G9a triggers DNA damage response and inhibits colorectal
      cancer cells proliferation may define G9a as potential oncotarget in CRC. 

PMID- 25595901
TI  - Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small
      cell lung cancer.
AB  - RNA interference (RNAi) is a powerful gene-silencing platform for cancer
      treatment. Previously, we demonstrated that ribophorin II (RPN2), which is part
      of the N-oligosaccharyl transferase complex, regulates docetaxel sensitivity and
      tumor lethal phenotypes in breast cancer. However, the molecular functions and
      clinical relevance of RPN2 in non-small-cell lung cancer (NSCLC) remain unknown.
      Here, we examined RPN2 expression in tumor specimens from recurrent NSCLC
      patients after resection (n = 32 and = 177) and assessed the correlation between
      RPN2 expression and various clinical features. We also investigated whether RPN2
      affects cancer malignancy in vitro and tumor growth and drug resistance in vivo.
      Our data show that RPN2 expression confers early and distant recurrence as well
      as poor survival in NSCLC patients. Furthermore, RPN2 silencing suppressed cell
      proliferation and invasiveness, and increased the sensitivity to chemotherapeutic
      drugs in vitro. Remarkably, we found that intrinsic apoptosis signaling is the
      mechanism of cell death involved with RPN2 knockdown. Strikingly, RPN2 silencing
      repressed tumorigenicity and sensitized the tumors to cisplatin treatment, which
      led to the longer survival of NSCLC-bearing mice. In conclusion, these data
      suggest that RPN2 is involved in the regulation of lethal cancer phenotypes and
      represents a promising new target for RNAi-based medicine against NSCLC. 

PMID- 25595902
TI  - Mitochondrial translocation and interaction of cofilin and Drp1 are required for
      erucin-induced mitochondrial fission and apoptosis.
AB  - Cofilin is a member of the actin-depolymerizing factor (ADF) family protein,
      which plays an essential role in regulation of the mitochondrial apoptosis. It
      remains unclear how cofilin regulates the mitochondrial apoptosis. Here, we
      report for the first time that natural compound 4-methylthiobutyl isothiocyanate
      (erucin) found in consumable cruciferous vegetables induces mitochondrial fission
      and apoptosis in human breast cancer cells through the mitochondrial
      translocation of cofilin. Importantly, cofilin regulates erucin-induced
      mitochondrial fission by interacting with dynamin-related protein (Drp1).
      Knockdown of cofilin or Drp1 markedly reduced erucin-mediated mitochondrial
      translocation and interaction of cofilin and Drp1, mitochondrial fission, and
      apoptosis. Only dephosphorylated cofilin (Ser 3) and Drp1 (Ser 637) are
      translocated to the mitochondria. Cofilin S3E and Drp1 S637D mutants, which
      mimick the phosphorylated forms, suppressed mitochondrial translocation, fission,
      and apoptosis. Moreover, both dephosphorylation and mitochondrial translocation
      of cofilin and Drp1 are dependent on ROCK1 activation. In vivo findings confirmed
      that erucin-mediated inhibition of tumor growth in a breast cancer cell xenograft
      mouse model is associated with the mitochondrial translocation of cofilin and
      Drp1, fission and apoptosis. Our study reveals a novel role of cofilin in
      regulation of mitochondrial fission and suggests erucin as a potential drug for
      treatment of breast cancer. 

PMID- 25595903
TI  - CD117+ cells in the circulation are predictive of advanced prostate cancer.
AB  - Circulating tumor cells (CTCs) are associated with cancer progression,
      aggressiveness and metastasis. However, the frequency and predictive value of
      CTCs in patients remains unknown. If circulating cells are involved in tumor
      aggressiveness and metastasis, then cell levels should decline upon tumor removal
      in localized cancer patients, but remain high in metastatic patients.
      Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34
      positive cell percentages in the blood of patients undergoing radical
      prostatectomy for localized cancer were assessed by flow cytometry prior to
      intervention and 1-3 months postoperatively. Only circulating CD117+ cell
      percentages decreased after radical prostatectomy, increased with cancer
      progression and correlated with high PSA values. Notably, postoperative CD117+
      levels did not decrease in patients experiencing biochemical recurrence. In a
      xenograft model, CD117-enriched tumors were more vascularized and aggressive.
      Thus, CD117 expression on CTCs promotes tumor progression and could be a
      biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.

PMID- 25595904
TI  - A novel orally active water-soluble inhibitor of human glutathione transferase
      exerts a potent and selective antitumor activity against human melanoma
      xenografts.
AB  - We designed and synthesized two novel nitrobenzoxadiazole (NBD) analogues of the
      anticancer agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol
      (NBDHEX). The new compounds, namely MC3165 and MC3181, bear one and two oxygen
      atoms within the hydroxy-containing alkyl chain at the C4 position of the NBD
      scaffold, respectively. This insertion did not alter the chemical reactivity with
      reduced glutathione, while it conferred a remarkable increase in water
      solubility. MC3181 was more selective than NBDHEX towards the target protein,
      glutathione transferase P1-1, and highly effective in vitro against a panel of
      human melanoma cell lines, with IC50 in the submicromolar-low micromolar range.
      Interestingly, the cellular response to MC3181 was cell-type-specific; the
      compound triggered a JNK-dependent apoptosis in the BRAF-V600E-mutated A375
      cells, while it induced morphological changes together with an increase in
      melanogenesis in BRAF wild-type SK23-MEL cells. MC3181 exhibited a remarkable
      therapeutic activity against BRAF-V600E-mutant xenografts, both after intravenous
      and oral administration. Outstandingly, no treatment-related signs of toxicity
      were observed both in healthy and tumor-bearing mice after single and repeated
      administrations. Taken together, these results indicate that MC3181 may represent
      a potential novel therapeutic opportunity for BRAF-mutated human melanoma, while
      being safe and water-soluble and thus overcoming all the critical aspects of
      NBDHEX in vivo.

PMID- 25595905
TI  - GOT1/AST1 expression status as a prognostic biomarker in pancreatic ductal
      adenocarcinoma.
AB  - Prognostication in pancreatic ductal adenocarcinoma (PDAC) remains a challenge.
      Recently, a link between mutated KRAS and glutamic-oxaloacetic transaminase
      (GOT1/AST1) has been described as part of the metabolic reprogramming in PDAC.
      The clinical relevance of this novel metabolic KRAS-GOT1 link has not been
      determined in primary human patient samples. Here we studied the GOT1 expression
      status as a prognostic biomarker in PDAC. We employed three independent PDAC
      cohorts with clinicopathological- and follow-up data: a) ICGC, comprising 57
      patients with whole-exome sequencing and genome-wide expression profiling; b)
      ULM, composed of 122 surgically-treated patients with tissue-samples and KRAS
      status; c) a validation cohort of 140 primary diagnostic biopsy samples. GOT1
      expression was assessed by RNA level (ICGC) or immunolabeling (ULM/validation
      cohort). GOT1 expression varied (ICGC) and correlation with the KRAS mutation-
      and expression status was imperfect (P = 0.2, ICGC; P = 0.8, ULM).
      Clinicopathological characteristics did not differ when patients were separated
      based on GOT1 high vs. low (P = 0.08-1.0); however, overall survival was longer
      in patients with GOT1-expressing tumors (P = 0.093, ICGC; P = 0.049, ULM).
      Multivariate analysis confirmed GOT1 as an independent prognostic marker (P =
      0.009). Assessment in univariate (P = 0.002) and multivariate models in the
      validation cohort (P = 0.019), containing 66% stage IV patients, confirmed the
      independency of GOT1. We propose the GOT1 expression status as a simple and
      reliable prognostic biomarker in pancreatic ductal adenocarcinoma.

PMID- 25595906
TI  - MicroRNA-500 sustains nuclear factor-kappaB activation and induces gastric cancer
      cell proliferation and resistance to apoptosis.
AB  - Ubiquitin deconjugation of key signalling molecules by deubiquitinases (DUBs)
      such as cylindromatosis (CYLD), A20, and OTU deubiquitinase 7B (OTUD7B) has
      emerged as an important regulatory mechanism in the downregulation of NF-kappaB
      signalling and homeostasis. However, how these serial negative regulations are
      simultaneously disrupted to result in constitutive activation of NF-kappaB
      signalling in cancers remains puzzling. Here, we report that the miR-500 directly
      repressed the expression of CYLD, OTUD7B, and the A20 complex component Tax1
      binding protein 1 (TAX1BP1), leading to ubiquitin conjugation of receptor
      interacting protein 1 (RIP1) and sustained NF-A B activation. Furthermore, we
      found that miR-500 promoted gastric cancer cell proliferation, survival, and
      tumorigenicity. Importantly, miR-500 was upregulated in gastric cancer and was
      highly correlated with malignant progression and poor survival. Hence, we report
      the uncovering of a novel mechanism for constitutive NF-kappaB activation,
      indicating the potentially pivotal role of miR-500 in the progression of gastric
      cancer. 

PMID- 25595907
TI  - Androgen receptors beyond prostate cancer: an old marker as a new target.
AB  - Androgen receptors (ARs) play a critical role in the development of prostate
      cancer. Targeting ARs results in important salutary effects in this malignancy.
      Despite mounting evidence that ARs also participate in the pathogenesis and/or
      progression of diverse tumors, exploring the impact of hormonal manipulation of
      these receptors has not been widely pursued beyond prostate cancer. This review
      describes patterns of AR expression in a spectrum of cancers, and the potential
      to exploit this knowledge in the clinical therapeutic setting. 

PMID- 25595910
TI  - DNA replication stress as an Achilles' heel of cancer.

PMID- 25595908
TI  - Specific and redundant activities of ETV1 and ETV4 in prostate cancer
      aggressiveness revealed by co-overexpression cellular contexts.
AB  - Genomic rearrangements involving ETS transcription factors are found in 50-70% of
      prostate carcinomas. While the large majority of the rearrangements involve ERG,
      around 10% involve members of the PEA3 subfamily (ETV1, ETV4 and ETV5). Using a
      panel of prostate cancer cell lines we found co-overexpression of ETV1 and ETV4
      in two cell line models of advanced prostate cancer (MDA-PCa-2b and PC3) and
      questioned whether these PEA3 family members would cooperate in the acquisition
      of oncogenic properties or show functional redundancy. Using shRNAs we found that
      ETV1 and ETV4 have partially overlapping functions, with ETV1 being more relevant
      for cell invasion and ETV4 for anchorage-independent growth. In vitro expression
      signatures revealed the regulation of both specific and shared candidate targets
      that may resemble cellular mechanisms in vivo by interaction with the same
      intermediate partners. By combining the phenotypic impact data and the gene
      expression profiles of in vitro models with clinico-pathological features and
      gene expression profiles of ETS-subtyped tumors, we identified a set of eight
      genes associated with advanced stage and a set of three genes associated with
      higher Gleason score, supporting an oncogenic role of ETV1 and ETV4
      overexpression and revealing gene sets that may be useful as prognostic markers. 

PMID- 25595911
TI  - CD80-CD28 signaling controls the progression of inflammatory colorectal
      carcinogenesis.
AB  - In patients with ulcerative colitis (UC) the cumulative risk of colon cancer is
      lower than the actual rate of dysplasia suggesting an efficient immune
      surveillance mechanism. Since the co-stimulatory molecule CD80 is overexpressed
      in dysplastic colonic mucosa of UC patients and T-cell activation entails
      effective costimulation, we aimed to evaluate the functional implication of CD80
      signaling in colonic UC-associated carcinogenesis. In humans, we observed that
      the percentage of CD80+ and HLA-A+ IEC was increased in the dysplastic colonic
      mucosa of UC patients. In vitro, IEC activated CD8+ T-cells through a CD80
      dependent pathway. Finally, in the AOM/DSS-induced colonic adenocarcinoma model
      CD80 signaling inhibition significantly increased the frequency and extension of
      high-grade dysplasia, whereas enhancing CD80 activity with an anti-CTLA4 antibody
      significantly decreased colonic dysplasia. In conclusion, CD80 signaling between
      IEC and T-cells represents a key factor controlling the progression from low to
      high grade dysplasia in inflammatory colonic carcinogenesis.

PMID- 25595912
TI  - LCK over-expression drives STAT5 oncogenic signaling in PAX5 translocated BCP-ALL
      patients.
AB  - The PAX5 gene is altered in 30% of BCP-ALL patients and PAX5 chromosomal
      translocations account for 2-3% of cases. Although PAX5 fusion genes
      significantly affect the transcription of PAX5 target genes, their role in
      sustaining leukemia cell survival is poorly understood. In an in vitro model of
      PAX5/ETV6 leukemia, we demonstrated that Lck hyper-activation, and down
      regulation of its negative regulator Csk, lead to STAT5 hyper-activation and
      consequently to the up-regulation of the downstream effectors, cMyc and Ccnd2.
      More important, cells from PAX5 translocated patients show LCK up-regulation and
      over-activation, as well as STAT5 hyper-phosphorylation, compared to PAX5 wt and
      PAX5 deleted cases. As in BCR/ABL1 positive ALL, the hyper-activation of STAT5
      pathway can represent a survival signal in PAX5 translocated cells, alternative
      to the pre-BCR, which is down-regulated. The LCK inhibitor BIBF1120 selectively
      reverts this phenomenon both in the murine model and in leukemic primary cells.
      LCK inhibitor could therefore represent a suitable candidate drug to target this
      subgroup of ALL patients. 

PMID- 25595913
TI  - "I can't stop worrying about everything"-experiences of rural Bangladeshi women
      during the first postpartum months.
AB  - Over recent years, researchers have found evidence which indicates that the
      prevalence of postpartum depressive symptoms crosses cultural boundaries and is
      reported to be at least as high in non-Western countries as in Western countries.
      However, qualitative studies about new mothers' experiences from non-Western
      countries, such as Bangladesh, are rare, particularly in rural areas. This study
      aims to describe the experiences and concerns of rural Bangladeshi mothers with
      postpartum depressive symptoms. Open narrative interviews were conducted with 21
      mothers with depressive symptoms 2-3 months postpartum, consecutively selected
      from a longitudinal study about prevalence and risk factors of perinatal
      depressive symptoms. Inductive content analysis was used to analyse data and
      three themes emerged: family dynamics, living at the limits of survival, and role
      of the cultural context after childbirth. These themes were based on six
      categories and 15 subcategories. The findings show that troublesome family
      relationships, including intimate partner violence and violence in the family,
      influenced the mothers' mental well-being. They and their families lived at the
      limit of survival and the mothers expressed fear and worries about their insecure
      situation regarding economic difficulties and health problems. They felt sorry
      for being unable to give their infants a good start in life and sad because they
      could not always follow the traditional norms related to childbirth. Thus, it is
      important to focus on the depressive symptoms among new mothers and offer
      counselling to those showing depressive symptoms, as the cultural traditions do
      not always alleviate these symptoms in the changing Bangladeshi society today. 

PMID- 25595909
TI  - Prostate cancer stem cells: deciphering the origins and pathways involved in
      prostate tumorigenesis and aggression.
AB  - The cells of the prostate gland are dependent on cell signaling pathways to
      regulate their growth, maintenance and function. However, perturbations in key
      signaling pathways, resulting in neoplastic transformation of cells in the
      prostate epithelium, are likely to generate subtypes of prostate cancer which may
      subsequently require different treatment regimes. Accumulating evidence supports
      multiple sources of stem cells in the prostate epithelium with distinct cellular
      origins for prostate tumorigenesis documented in animal models, while human
      prostate cancer stem-like cells (PCSCs) are typically enriched by cell culture,
      surface marker expression and functional activity assays. As future therapies
      will require a deeper understanding of its cellular origins as well as the
      pathways that drive PCSC maintenance and tumorigenesis, we review the molecular
      and functional evidence supporting dysregulation of PI3K/AKT, RAS/MAPK and STAT3
      signaling in PCSCs, the development of castration resistance, and as a novel
      treatment approach for individual men with prostate cancer. 

PMID- 25595915
TI  - A multiplex PCR assay for the simultaneous detection of Chlamydia trachomatis,
      Neisseria gonorrhoeae, and Trichomonas vaginalis.
AB  - INTRODUCTION: For developing countries, sexually transmitted infections (STIs)
      and their complications are ranked in the top 5 disease categories for which
      adults seek medical treatment. Chlamydia trachomatis (CT), Neisseria gonorrhoeae
      (NG), and Trichomonas vaginalis (TV) are the three most common STIs worldwide,
      with TV accounting for over half of the cases. In developing countries,
      traditional methods for diagnosing STIs are laborious, often not very sensitive,
      and have a long turnaround time with most recent commercially available
      diagnostic tests targeting one or, at most, two of these STIs at a time. Here, we
      describe the development of a highly sensitive, rapid and affordable sample-to
      answer multiplex PCR-based assay for the simultaneous detection of Trichomonas
      vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis. MATERIALS AND
      METHODS: We designed a multiplex PCR assay for the detection of 4 targets (CT,
      TV, NG, and process/PCR control) using melt curve analysis. To establish the
      limit of detection (LOD) for each pathogen, we used previously extracted and
      quantified TV, NG, and CT genomic DNA (Vircell, Spain). For each target, the LOD
      was determined by lowering its copy number while increasing the other two STI
      loads in a stepwise fashion. The process/PCR control remained constant in the
      optimized assay and was spiked into each sample before extraction. For a
      concordance study, we tested urine, vaginal and rectal swab specimens from 26
      patients positive for one or more of the tested STIs. In addition, 56 liquid
      cytology specimens (Thinprep) were used to assess specificity. RESULTS: This
      assay has a turnaround time of less than 2h and has a limit of detection as low
      as 7-31 copies for each STI in the presence of the other 2 targets. Our assay
      also demonstrated 100% concordance with 26 known clinical samples from urine,
      vaginal and rectal swab specimens. TV, NG, CT, and our process/PCR control were
      consistently identified at 78 degrees C, 82.3 degrees C, 85.7 degrees C, and ~92
      degrees C, respectively. When applied to DNA extracted from residual Thinprep
      specimens, the assay was negative in 54/56 samples. Two samples were found to be
      co-infected with CT. CONCLUSIONS: Our multiplex assay combines a rapid and cost
      effective approach to molecular diagnostics with the versatility required for use
      within a variety of laboratory settings. These performance characteristics make
      this multiplex STI assay highly suitable for use in a clinical laboratory.

PMID- 25595916
TI  - The importance of extracellular matrix for cell function and in vivo likeness.
AB  - OBJECTIVE: Fibrotic diseases may be described as a disease of the extracellular
      matrix, where the balance between matrix formation and degradation has been
      shifted leading to an accumulation of matrix. Currently a fit for purpose model
      and readily available approach are adapted when doing cell cultures, which may
      not reflect physiology and pathophysiology optimally. The aim of this review is
      to draw special attention to the similarities and differences of current state of
      the art in vitro and ex vivo models, with special focus on the proteins, cell
      cell interactions, and correct matrix composition, which may be a better
      representative of in vivo conditions in a disease where the extracellular matrix
      is the central player. METHODS: We reviewed current literature with emphasis on
      the role of the extracellular matrix in health and disease, different fibrotic
      disease models, and highlighting the importance of this when looking at
      translational science. CONCLUSION: To further our fibrotic research one paramount
      problem is to fundamentally understand the core of the disease, the production
      and degradation of the extracellular matrix. For a surprisingly long time the ECM
      has been underestimated until recently, with the discovery that the ECM may
      control cell phenotype through cell-matrix interactions. This highlights the need
      of a native ECM when investigating pathways and response to potential therapy.
      Clearly, both in vitro and in vivo models provide fit to purpose benefits, but in
      particular for the fibrosis field we may ask, do single cell cultures in
      monolayers recapitulate the complicated ECM environment controlling cell fate?

PMID- 25595914
TI  - Molecular diagnosis of orbital inflammatory disease.
AB  - Orbital inflammatory diseases include thyroid eye disease (TED), granulomatosis
      with polyangiitis (GPA), sarcoidosis, and nonspecific orbital inflammation
      (NSOI). Histopathological diagnosis usually relies on the clinical context and is
      not always definitive. Gene expression profiling provides diagnostic and
      therapeutic information in several malignancies, but its role in evaluating
      nonmalignant disease is relatively untested. We hypothesized that gene expression
      profiling could provide diagnostic information for NSOI. We collected formalin
      fixed, paraffin-embedded orbital biopsies from 10 institutions and 83 subjects
      including 25 with thyroid eye disease, 25 nonspecific orbital inflammation, 20
      healthy controls, 6 with granulomatosis with polyangiitis, and 7 with
      sarcoidosis. Tissues were divided into discovery and validation sets. Gene
      expression was quantified using Affymetrix U133 Plus 2.0 microarrays. A random
      forest statistical algorithm based on data from 39 probe sets identified
      controls, GPA, or TED with an average accuracy of 76% (p=0.02). Random forest
      analysis indicated that 52% of tissues from patients with nonspecific
      inflammation were consistent with a diagnosis of GPA. Molecular diagnosis by gene
      expression profiling will augment clinical data and histopathology in
      differentiating forms of orbital inflammatory disease. 

PMID- 25595917
TI  - Comment on: A retrospective comparison of early results of conversion of failed
      gastric banding to sleeve gastrectomy or gastric bypass.

PMID- 25595918
TI  - Comment on: Worthy or not? Six Year Experience of Revisional Bariatric Surgery
      from an Asian Centre of Excellence.

PMID- 25595920
TI  - Laparoscopic revision of distal Roux-en-Y gastric bypass to duodenal switch for
      weight loss failure and symptoms.

PMID- 25595921
TI  - [Multidisciplinary outpatient care program vs. usual care : Cost-benefit analysis
      in patients with chronic low back pain].
AB  - BACKGROUND: Chronic low back pain (CLBP) is a major health problem in
      industrialized nations and is associated with very high total costs. These costs
      are split between direct costs brought about by the utilization of health care
      services and indirect costs due to back pain-related loss of productivity.
      Despite the existence of some evidence about the effectiveness of a
      multidisciplinary outpatient care programmes in Germany, the economic benefit of
      these programmes has not yet been studied in detail. OBJECTIVE: To provide an
      economic evaluation of the cost benefits of a multidisciplinary outpatient care
      programme for patients with chronic low back pain (CLBP) compared to those
      undergoing conventional care. MATERIALS AND METHODS: An economic evaluation was
      performed in 514 patients who have been diagnosed with LBP. Two interventions
      will be compared: (1) a multidisciplinary outpatient care programme consisting of
      education, activity programmes, cognitive behavioural therapy, work hardening and
      functional restoration and (2) the usual noninvasive care provided by medical
      specialists and health care professionals. In all, 257 patients were involved in
      a 4 week multidisciplinary outpatient care programme, while the other 257 were
      subject to conventional care. RESULTS: The total costs per patient were estimated
      to be <euro>10,584.14 (+/-<euro> 9,730.87) after 1 year in the group with the
      multidisciplinary care programme. The results show a significant reduction in the
      total amount of costs <euro>3,161.63 (range <euro>2,845.30-3,477.96) compared to
      the usual care group. However, the direct costs are minor (6-12%) compared to the
      indirect costs (80-93%). CONCLUSION: This study provides important information
      which is of value for decision-making and making an adequate allocation of
      medical resources for patients with CLBP. A multidisciplinary outpatient care
      programme can facilitate rapid return to work.

PMID- 25595919
TI  - Technical factors associated with anastomotic leak after Roux-en-Y gastric
      bypass.
AB  - BACKGROUND: Anastomotic leak is one of the most serious complications after Roux
      en-Y gastric bypass (RYGB). Our objective was to examine the relationship between
      technical factors and incidence of clinically relevant anastomotic leak after
      RYGB in longitudinal assessment of bariatric surgery (LABS). The setting of the
      study was 11 bariatric centers in the United States, university, and private
      practice. METHODS: Patient characteristics, technical factors of surgery, and
      postoperative outcomes were assessed by trained researchers using standardized
      protocols. Correlation of surgical factors of patients undergoing RYGB (n = 4444)
      with the incidence of postoperative anastomotic leak was assessed by univariate
      chi(2) analysis. RESULTS: Forty-four participants (1.0%, 95% CI .7%-1.3%)
      experienced a clinically relevant anastomotic leak. Of these, 39 (89%) underwent
      abdominal reoperation and 3 (7%) died. Technical factors associated with
      anastomotic leak were open surgery (P<.0001), revision surgery (P<.0001), and use
      of an abdominal drain (P = .02). Provocative leak testing, method of
      gastrojejunostomy, and use of fibrin sealant were not associated with anastomotic
      leak. CONCLUSIONS: Anastomotic leak after RYGB was rare (1.0%). Most cases
      required reintervention; however, the majority (93%) recovered from this event.
      Open surgery, revision surgery, and routine drain placement were associated with
      increased leak rate. Some of these findings may be due to differences in
      preoperative patient risk.

PMID- 25595923
TI  - Postoperative atrial fibrillation is not pulmonary vein dependent: results from a
      randomized trial.
AB  - BACKGROUND: Although often short-lived and self-limiting, postoperative atrial
      fibrillation (POAF) is a well-recognized postoperative complication of cardiac
      surgery and is associated with a 2-fold increase in cardiovascular mortality and
      morbidity. OBJECTIVE: Our aim was to determine whether intraoperative bilateral
      pulmonary vein radiofrequency ablation decreases the incidence of POAF in
      patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of
      175 patients undergoing CABG was prospectively randomized to undergo adjuvant
      bilateral radiofrequency pulmonary vein ablation in addition to CABG (group A; n
      = 89) or CABG alone (group B; n = 86). Intraoperative pulmonary vein isolation
      was confirmed by the inability to pace the heart via the pulmonary veins after
      ablation. All patients received postoperative beta-blocker. RESULTS: There was no
      difference in the incidence of POAF in the treatment group who underwent adjuvant
      pulmonary vein ablation (group A; 37.1%) compared with the control group who did
      not (group B; 36.1%) (P = .887). There were no differences in postoperative
      inotropic support, antiarrhythmic drug use, need for oral anticoagulation, and
      complication rates. The mean length of postoperative hospital stay was 8.2 +/-
      6.5 days in the ablation group and 6.7 +/- 4.6 days in the control group (P <
      .001). CONCLUSION: Adjuvant pulmonary vein isolation does not decrease the
      incidence of POAF or its clinical impact but increases the mean length of stay in
      the hospital. The mechanism of POAF does not appear to depend on the pulmonary
      veins.

PMID- 25595924
TI  - 69-year-old man with a history of atrial fibrillation.

PMID- 25595925
TI  - Reply to the Editor--Concern regarding adult congenital heart disease arrhythmia
      guidelines.

PMID- 25595922
TI  - The association of left atrial low-voltage regions on electroanatomic mapping
      with low attenuation regions on cardiac computed tomography perfusion imaging in
      patients with atrial fibrillation.
AB  - BACKGROUND: Previous studies have shown that contrast-enhanced multidetector
      computed tomography (CE-MDCT) could identify ventricular fibrosis after
      myocardial infarction. However, whether CE-MDCT can characterize atrial low
      voltage regions remains unknown. OBJECTIVE: The purpose of this study was to
      examine the association of CE-MDCT image attenuation with left atrial (LA) low
      bipolar voltage regions in patients undergoing repeat ablation for atrial
      fibrillation recurrence. METHODS: We enrolled 20 patients undergoing repeat
      ablation for atrial fibrillation recurrence. All patients underwent preprocedural
      3-dimensional CE-MDCT of the LA, followed by voltage mapping (>100 points) of the
      LA during the ablation procedure. Epicardial and endocardial contours were
      manually drawn around LA myocardium on multiplanar CE-MDCT axial images.
      Segmented 3-dimensional images of the LA myocardium were reconstructed.
      Electroanatomic map points were retrospectively registered to the corresponding
      CE-MDCT images. RESULTS: A total of 2028 electroanatomic map points obtained in
      sinus rhythm from the LA endocardium were registered to the segmented LA wall CE
      MDCT images. In a linear mixed model, each unit increase in the local image
      attenuation ratio was associated with 25.2% increase in log bipolar voltage (P =
      .046) after adjusting for age, sex, body mass index, and LA volume, as well as
      clustering of data by patient and LA regions. CONCLUSION: We demonstrate that the
      image attenuation ratio derived from CE-MDCT is associated with LA bipolar
      voltage. The potential ability to image fibrosis via CE-MDCT may provide a useful
      alternative in patients with contraindications to magnetic resonance imaging.

PMID- 25595926
TI  - Accuracy of patient perception of their prevailing rhythm: a comparative analysis
      of monitor data and questionnaire responses in patients with atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) guidelines recommend that symptom relief be
      a primary goal in management. However, patient perception of their prevailing
      rhythm is often inaccurate, complicating symptom-targeted treatment. OBJECTIVE:
      The purpose of this study was to evaluate the accuracy of patient perception of
      their prevailing rhythm and identify factors that predict inaccuracies. METHODS:
      Demographic and health status data were captured by questionnaires for 458
      outpatients with documented AF. AF burden (%) was captured by 1-week continuous
      heart monitors. Patients estimated the length and frequency of their AF episodes
      by completing the AF Symptom Severity questionnaire. Patient reports were
      compared to AF burden, and outliers were identified and broken into 2 groups:
      patients with AF burden <10% who indicated near-continuous AF (overestimators)
      and patients with AF burden >90% who estimated little to no AF (underestimators).
      Multinomial logistic regression was used to identify predictors of inaccuracies
      (over- or underestimators). RESULTS: By continuous monitor, 15% of patients were
      found to be over- or underestimators. Persistent AF, female sex, older age,
      anxiety, and depression were predictive of inaccurate patient perception.
      Persistent AF, female sex, and older age were predictive of underestimating,
      while mood disorders (anxiety and depression) were predictive of overestimating.
      The prevalence of underestimators was nearly twice that of overestimators.
      CONCLUSION: Sex, age, and mood disorders are among factors that lead to
      inaccurate patient perception of their prevailing rhythm in patients with AF.
      Such modulating factors should be considered when evaluating treatment
      strategies. Consideration should be given to more liberal use of heart monitors
      in these patient populations to better target therapy.

PMID- 25595927
TI  - Dynamic regulation of atrial coronary blood flow in healthy adult pigs.
AB  - BACKGROUND: There are several indications for a mismatch between atrial oxygen
      supply and demand during atrial fibrillation (AF), but atrial coronary flow
      regulation has not been investigated extensively. OBJECTIVE: The purpose of this
      study was to characterize the dynamic regulation of atrial coronary flow in pigs.
      METHODS: In anesthetized open-chest pigs, Doppler flow probes were placed around
      left atrial (LA) and left ventricular (LV) branches of the circumflex artery.
      Pressures and work indices were measured simultaneously. Systolic and diastolic
      flow contribution, flow response kinetics, and relationship between pressures,
      work, and flow were investigated during sinus rhythm, atrial pacing, and acute
      AF. RESULTS: During atrial systole, LA flow decreased. Only 2% of total LA flow
      occurred during atrial systole. Pacing with 2:1 AV block and infusion of
      acetylcholine revealed that atrial contraction itself impeded atrial coronary
      flow. The response to sudden changes in heart rate was slower in LA compared to
      LV. Both LA and LV vascular conductance were positively correlated with work.
      After the cessation of acute AF, the LA showed a more pronounced phase of
      supranormal vascular conductance than the LV, indicating a period of atrial
      reactive hyperemia. CONCLUSION: In healthy adult pigs, atrial coronary flow is
      impeded by atrial contraction. Although atrial coronary blood flow is positively
      correlated with atrial external work, it reacts more slowly to changes in rate
      than ventricular flow. The occurrence of a pronounced hyperemic phase after acute
      AF supports the notion of a significant supply-demand mismatch during AF.

PMID- 25595928
TI  - Optimizing Patient Selection and Outcomes for Surgical Treatment of GERD and
      Achalasia.
AB  - OPINION STATEMENT: Gastroesophageal reflux disease is a common disorder in the
      United States and other western countries. In addition to troublesome symptoms,
      this condition is associated with impaired quality of life and the potential for
      disease progression to esophageal adenocarcinoma. Acid suppression medications
      are extremely effective for the relief of heartburn symptoms, but don't address
      the physiologic derangements that cause reflux. The goal of an antireflux
      procedure is to correct these defects and abolish the dietary and lifestyle
      compromises that accompany medical therapy for gastroesophageal reflux. The
      Nissen fundoplication has a long and well-established track record and new
      options such as the LINX magnetic sphincter augmentation device allow correction
      of reflux with fewer side-effects than a fundoplication in appropriate patients.
      These options should be considered in patients incompletely satisfied on medical
      therapy and in those with risk factors for disease progression. The role of these
      therapies in patients with gastroesophageal reflux disease will be reviewed in
      this chapter. Achalasia is an uncommon motility disorder of the esophagus that
      leads to profound dysphagia symptoms and greatly impaired alimentary
      satisfaction. Pneumatic dilation offers an endoscopic approach to the management
      of these patients, but often requires repeated dilatations due to the
      inconsistent disruption of the lower esophageal sphincter with this technique. An
      alternative is a laparoscopic Heller myotomy, which offers precise division of
      the muscle of the lower esophageal sphincter, but requires incisions and
      lifestyle restrictions while healing. A new therapy, per-oral endoscopic myotomy,
      allows the precise division of the lower esophageal sphincter muscle as in a
      laparoscopic myotomy, but is done endoscopically with no external incisions. The
      role of these therapies in patients will be reviewed in this chapter.

PMID- 25595929
TI  - Management of severe ulcerative colitis.
AB  - OPINION STATEMENT: Acute severe steroid-refractory ulcerative colitis (ASUC)
      provides challenges for physicians and surgeons who manage these patients. When a
      patient is diagnosed with ASUC, they should be admitted for inpatient management
      including intravenous corticosteroids, venous thromboembolism prophylaxis, oral
      or enteral feeding if tolerated, and exclusion of infection including Clostridium
      difficile. Failure to improve by day 3 of corticosteroids requires escalation to
      medical rescue therapies such as infliximab or cyclosporine, or surgical
      management with colectomy. This chapter will review management of ASUC with a
      focus on the medical rescue options available.

PMID- 25595930
TI  - Therapeutic Manipulation of the Microbiome in IBD: Current Results and Future
      Approaches.
AB  - OPINION STATEMENT: Despite recent major strides in our understanding of the
      genetic and microbial influences that contribute to the development of the
      inflammatory bowel diseases (IBDs), their etiology continues to be enigmatic.
      Results from experiments in animal models of IBDs overwhelmingly support a causal
      role of the microbiota in these diseases, though whether such a cause-effect
      relationship exists in human IBDs is still uncertain. Therefore, virtually all
      currently approved and most often prescribed treatments for IBDs are directed
      toward the over-active immune response in these diseases rather than the
      intestinal bacteria. Nevertheless, there is an important need for non
      immunosuppressive therapies that may present a more favorable risk-benefit
      profile such as those that selectively target the disruptions in gut microbiota
      that accompany IBDs. This need has led to clinical trials of various microbial
      directed therapies including fecal microbial transplant, antibiotics, probiotics,
      and prebiotics. Unfortunately, these published studies, many of which are small,
      have generally failed to demonstrate a consistent benefit of these agents in
      IBDs, thus leading to slow acceptance of microbe-focused treatments for these
      conditions. In this article, we review and summarize the microbial basis for IBDs
      and the results of the most recent trials of fecal microbial transplant,
      antibiotics, probiotics, and prebiotics in IBDs. We also comment on possible
      safety concerns with these agents, speculate on why they have failed to show
      efficacy in certain clinical settings, and propose strategies to improve their
      usefulness.

PMID- 25595931
TI  - Differential gene transcription, biochemical responses, and cytotoxicity
      assessment in Pacific oyster Crassostrea gigas exposed to ibuprofen.
AB  - Pharmaceuticals, such as anti-inflammatory nonsteroidal drugs, are frequently
      detected in aquatic ecosystems. Studies about the effects of these substances in
      nontarget organisms, such as bivalves, are relevant. The aim of this study was to
      evaluate the effects on antioxidant status caused by ibuprofen (IBU) in oysters
      Crassostrea gigas exposed for 1, 4, and 7 days at concentrations 1 and 100 MUg L(
      1). Levels of IBU in tissues of oysters, as well as cell viability of hemocytes,
      were measured. The transcription of cytochrome P450 genes (CYP2AU2, CYP356A1,
      CYP3071A1, CYP30C1), glutathione S-transferase isoforms (GST-omega-like and GST
      pi-like), cyclooxygenase-like (COX-like), fatty acid binding protein-like (FABP
      like), caspase-like, heat shock protein-like (HSP70-like), catalase-like (CAT
      like), and the activity of catalase (CAT), glutathione peroxidase (GPx),
      glutathione reductase (GR), and glutathione S-transferase (GST) were also
      evaluated in the gills of oysters. The highest levels of IBU were observed in
      animals exposed to 100 MUg L(-1). A significant upregulation of CYP2AU1,
      CYP356A1, CYP3071A1, GST-omega-like, GST-pi-like, COX-like, and FABP-like was
      observed in oysters exposed to IBU under different experimental conditions.
      Oysters exposed to 1 MUg L(-1) for 7 days showed a significantly higher
      transcription of CYP2AU2, CYP356A1, CYP3071A1, GST-omega-like, and GST-pi-like
      but lower GR activity. In conclusion, C. gigas exposed to environmentally
      relevant concentrations of IBU (1 MUg L(-1)) exhibited increased transcription of
      certain genes and alterations on antioxidant and auxiliary enzymes, which could,
      in the the long term, cause damages to exposed organisms.

PMID- 25595932
TI  - Organochlorine pesticides and their metabolites in human breast milk from
      Shanghai, China.
AB  - Organochlorine pesticides (OCPs) are persistent organic pollutants that could
      cause deleterious effects on human health. Breast milk represents a noninvasive
      specimen source to assess maternal and infant exposure to OCPs. This study
      recruited 142 pregnant mothers in 2011-2012 in Shanghai, China, and their breast
      milk samples were collected during lactation and analyzed for 27 OCP compounds.
      Detection rates were in a range of 65.5 to 100 %. In particular, metabolites of
      2,2-bis(chlorophenyl)-1,1,1-trichloroethane (DDT) such as 2-chloro-1,1-bis(4
      chlorophenyl)ethylene (DDMU), 2,2-bis(4-chlorophenyl)ethanol (DDOH), bis(4
      chlorophenyl)ketone (DBP), and 4,4'-dichlorodiphenylmethane (DDM) were detected
      in most milk samples. DDTs, hexachlorobenzene (HCB), and hexachlorocyclohexane
      (HCH) were dominant OCPs with mean levels of 316, 49.8, and 41.5 ng/g lipid
      content, respectively, whereas levels of methoxychlor, ?Drins, ?Heptachlor,
      ?Chlordane, and ?Endosulfan were fairly low (0.87-5.6 ng/g lipid content). Milk
      concentrations of OCPs were weakly correlated with maternal age, body weight, and
      body mass indexes (BMIs). ?OCPs in this study were much lower than those in human
      breast milk samples collected in 2002 and 2007. Consumption of higher amounts of
      fish was associated with higher milk levels of OCPs. Specific OCP patterns in
      breast milk samples from migrant mothers in Shanghai reflected features of OCP
      production, use, and exposure in their home provinces. The probabilistic exposure
      assessment model reveals that Shanghai infants were exposed to low levels of OCPs
      through breast milk consumption. However, infants as the vulnerable group might
      be subject to the potential additive and/or synergistic health effects from
      complex OCP exposure.

PMID- 25595933
TI  - Joint toxicity of chlorpyrifos, atrazine, and cadmium at lethal concentrations to
      the earthworm Eisenia fetida.
AB  - Contaminants in the environment often occur as complex mixtures, and their
      combined effect may exhibit toxicity to organisms. Risk assessments based on
      individual components tend to underestimate the effects associated with toxic
      action of mixtures. Toxicity studies on chemical mixtures are urgently required
      to assess their potential combined toxicities. The combination index (CI)
      isobologram method was used to study chemical interactions to determine the
      nature of toxicological interactions of two pesticides chlorpyrifos and atrazine
      and a heavy metal cadmium toward earthworm Eisenia fetida by artificial soil and
      filter paper acute toxicity tests. The results showed that the binary mixture of
      chlorpyrifos and atrazine was antagonistic toward E. fetida at all f a levels in
      an artificial soil test. The combination of atrazine and Cd exhibited a slight
      degree of synergism throughout the exposure range, while chlorpyrifos plus Cd
      combination led to dual antagonistic/synergistic behavior. The nature of binary
      combinations in filter paper displayed opposite interaction to that in the
      artificial soil test, and the toxicity of ternary mixtures was not significantly
      synergistic than their binaries. The combination index (CI)-isobologram equation
      method could determine the interaction types for a series of effect levels of
      three chemicals in binary and ternary combinations in two types of acute
      earthworm tests. However, the nature of these interactions was not uniform along
      the f a level range in any of the two tests. Bioavailability, the nature of
      toxicological interaction, and the test organism need to be considered for
      understanding exposures and chemical measures. The synergistic effect for the
      particular binary combination suggests that a potential risk associated with the
      co-occurrence of these pollutants may still exist, which may have implications in
      risk assessment for the terrestrial environment. The combined effects between
      different contaminants might be influenced by the category of chemical, as well
      as the bioassay procedures. More studies of combined toxicities among these
      contaminants in the terrestrial environment should be conducted to identify the
      mixtures exhibiting synergistic pattern of interactions. 

PMID- 25595935
TI  - Reply to the letter to the editor 'Surrogate end points for overall survival.
      Festina lente (more haste, less speed)' by Braillon.

PMID- 25595934
TI  - Impact of age and medical comorbidity on adjuvant treatment outcomes for stage
      III colon cancer: a pooled analysis of individual patient data from four
      randomized, controlled trials.
AB  - BACKGROUND: Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil
      (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC);
      however, there is disagreement regarding oxaliplatin benefit in patients aged
      >70. In most analyses, the impact of medical comorbidity (MC) has not been
      assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were
      compared with respect to age and MC using pooled data from four randomized,
      controlled trials, selected for access to patient-level MC data and including
      commonly endorsed and utilized regimens. PATIENTS AND METHODS: Individual data
      from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were
      pooled, excluding bevacizumab-treated patients. Patients were grouped by
      treatment, MC (low versus high), or age (<70 versus >=70), and compared for
      disease-free survival (DFS), overall survival (OS), and adverse events (AEs).
      Multivariable Cox proportional hazards regression controlled for gender, T stage,
      and N stage. RESULTS: DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU
      regardless of age or MC, although benefits were modestly attenuated for patients
      aged >=70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and
      >=70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity
      Index <=1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National
      Cancer Institute Combined Index <=1 and >1 groups. OS was also significantly
      improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts
      and MC scores and higher in patients aged >=70. Oxaliplatin-relevant grade 3/4
      AEs, including neuropathy, were comparable across ages and MC scores.
      CONCLUSIONS: Results further support consideration of XELOX or FOLFOX as standard
      treatment options for the adjuvant management of stage III CC in all age groups
      and in patients with comorbidities, consistent with those who were eligible for
      these clinical trials.

PMID- 25595937
TI  - Ebola virus: understanding the 2014 outbreak.

PMID- 25595938
TI  - A technique for endobronchial ultrasound-guided fine needle aspiration.

PMID- 25595939
TI  - High-Attenuation Mucus in Allergic Bronchopulmonary Aspergillosis.

PMID- 25595936
TI  - Prevalence of the HOXB13 G84E germline mutation in British men and correlation
      with prostate cancer risk, tumour characteristics and clinical outcomes.
AB  - BACKGROUND: A rare recurrent missense variant in HOXB13 (rs138213197/G84E) was
      recently reported to be associated with hereditary prostate cancer. Population
      based studies have established that, since the frequency of this single
      nucleotide polymorphism (SNP) varies between geographic regions, the associated
      proportion of prostate cancer (PrCa) risk contribution is also highly variable by
      country. PATIENTS AND METHODS: This is the largest comprehensive case-control
      study assessing the prevalence of the HOXB13 G84E variant to date and is the
      first in the UK population. We genotyped 8652 men diagnosed with PrCa within the
      UK Genetic Prostate Cancer Study (UKGPCS) and 5252 healthy men from the UK
      ProtecT study. RESULTS: HOXB13 G84E was identified in 0.5% of the healthy
      controls and 1.5% of the PrCa cases, and it was associated with a 2.93-fold
      increased risk of PrCa [95% confidence interval (CI) 1.94-4.59; P = 6.27 * 10(
      8)]. The risk was even higher among men with family history of PrCa [odds ratio
      (OR) = 4.53, 95% CI 2.86-7.34; P = 3.1 * 10(-8)] and in young-onset PrCa
      (diagnosed up to the age of 55 years; OR = 3.11, 95% CI 1.98-5.00; P = 6.1 * 10(
      7)). There was no significant association between Gleason Score, presenting
      prostate specific antigen, tumour-node-metastasis (TNM) stage or NCCN risk group
      and carrier status. HOXB13 G84E was not associated with overall or cancer
      specific survival. We found that the polygenic PrCa risk score (PR score),
      calculated using the 71 known single-nucleotide polymorphisms (SNPs) associated
      with PrCa and the HOXB13 G84E variant act multiplicatively on PrCa risk. Based on
      the estimated prevalence and risk, this rare variant explains ~1% of the familial
      risk of PrCa in the UK population. CONCLUSIONS: The clinical importance of HOXB13
      G84E in PrCa management has not been established. This variant was found to have
      no effect on prognostic implications but could be used for stratifying screening,
      by identifying men at high risk. CLINICAL TRIALS NUMBERS: Prostate Testing for
      Cancer and Treatment (ProtecT): NCT02044172. UK GENETIC PROSTATE CANCER STUDY:
      Epidemiology and Molecular Genetics Studies (UKGPCS): NCT01737242.

PMID- 25595940
TI  - Geriatric assessement a key tool in the initial management of the elderly patient
      with community-acquired pneumonia.

PMID- 25595941
TI  - [E. Nohuz in reply to the article by H. Collinot et E. Azria entitled "Cervical
      pessary for preventing preterm birth". Gynecol Obstet Fertil 2013;41:260-1].

PMID- 25595942
TI  - [Hysteroscopic morcellation versus bipolar resection for endometrial polyp
      removal].
AB  - OBJECTIVE: The treatment of endometrial polyps is based on hysteroscopic
      resection. The aim of the current study was to compare the results associated
      with hysteroscopic morcellation and those observed with bipolar loop resection.
      PATIENTS AND METHODS: A single-center observational retrospective comparative
      study was performed, including 25 patients who underwent hysteroscopic resection
      of endometrial polyps from January 2012 to December 2013. The mean size of polyp
      was 9.2 mm in the group compared to 12.5mm in the resection group loop (P=0.06).
      RESULTS: Twelve patients underwent resection of the polyp morcellation with
      MyoSure((r)) and 13 with bipolar resection loop Versapoint((r)) 24F. The mean
      operative time was 16 minutes in morcellation group and 17 minutes in the bipolar
      resection group (P=0.76). Complete removal was achieved in 100% of cases in
      morcellation group and in bipolar loop resection. Regarding intraoperative and
      postoperative complications, no complication was observed in the two groups.
      DISCUSSION AND CONCLUSION: Results associated with hysteroscopic morcellation and
      bipolar loop resection seen to be comparable.

PMID- 25595943
TI  - [Uterine transplantation: is there a real demand?].
AB  - OBJECTIVES: To study the demand there is for uterus transplantation (UTx).
      PATIENTS AND METHODS: Recent media coverage of developments in UTx prompted
      associations of patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome and
      of women suffering from UI to contact us. We sent them anonymous questionnaires
      devised to sound out their attitude towards UTx and towards adoption and
      gestational surrogacy (GS). A clinical psychologist also carried out a
      qualitative discourse analysis. RESULTS: Sixty patients answered the
      questionnaire. Thirty-eight patients were married or living with a male partner.
      Seven patients had had a hysterectomy. Fifty-one patients had uterine agenesis.
      Of the 60 patients, 19 and 21, respectively, had ruled out the option of adoption
      or GS, and 11 would not envisage either possibility. Thirty-five patients were
      willing to take part in a clinical study into UTx despite the uncertainty of the
      outcome and the potential risks involved. Of these 35 volunteers, 23 were in a
      heterosexual relationship and aged <=35 years. DISCUSSION AND CONCLUSION: For
      women with UI the condition is all the more distressing because there is no
      medical solution for it. UTx could hold out hope for some of these patients
      despite the complexity of the procedure and the attendant risks. Because of the
      feelings of vulnerability engendered by UI, any UTx programme should provide full
      information to patients and ensure they are carefully screened and selected.

PMID- 25595944
TI  - [Management of vaginal infection following failure of a probabilistic treatment:
      is the vaginal swab really useful?].
AB  - OBJECTIVE: The aim of this observational national multi-centre study was to
      describe medical care of vaginal infections resisting a primary probabilistic
      treatment. PATIENTS AND METHODS: Two hundred and seventy female patients were
      included during a 9-month period (from 2013, March 20th to 2013, December 7th) by
      155 gynaecologists located throughout France. RESULTS: All patients were
      presenting a vulvo-vaginitis episode which started about three weeks ago and
      which was characterized by leucorrhea (93 % cases), itching (88 % cases) and/or
      vulvar and/or vaginal irritation (88 % cases). In most cases, this episode was
      previously treated by a short course of an azole antifungal medication. This
      treatment was initiated by the patient herself without any doctor's prescription
      in six out of 10 cases and had no influence on the evolution of the original
      clinical symptoms. Second line treatments included azole antifungal medications
      (56 % cases), local fixed combinations (antifungal agent and bactericidal
      antibiotic) (29 %), metronidazole (9 %), oral antibiotics (7.4 %). At the end of
      the treatment, 85 % patients recovered from vaginitis symptoms. The recovery rate
      was 82.6 % for patients who got a bacteriological examination and 87.6 % for
      patients who were treated without any bacteriological examination. The difference
      is not statistically significant. DISCUSSION AND CONCLUSION: These results seem
      to show that a probabilistic medical care is as effective as (but probably more
      economical than) a therapeutic strategy guided by the results of further
      examinations in case of failure of a primary treatment. This conclusion should be
      confirmed by a medico-economic comparison after randomization.

PMID- 25595945
TI  - [Surgery for deep infiltrating endometriosis before in vitro fertilization: no
      benefit for fertility?].
AB  - OBJECTIVE: Does surgery for deep infiltrating endometriosis (DIE) before in vitro
      fertilization (IVF) improve pregnancy and birth rate? PATIENTS AND METHODS:
      Cohort study of 177 consecutive patients with DIE related infertility and
      receiving IVF. Patients were divided into 3 groups according to surgical
      management decided during multidisciplinary team meeting. Group no surgery (NS)
      (n=65), group complete surgery (CS) with complete resection of all lesions (n=49)
      and group incomplete surgery (IS) with gestures improving ovaries accessibility
      for IVF and/or facilitating embryonic implantation (n=63). Pre-surgery clinical,
      MRI lesion locations, and history of IVF characteristics were analyzed with
      logistic regression. RESULTS: There was no significant difference in general and
      IVF characteristics and in the severity of endometriosis among the three groups
      (P=0.43). Overall pregnancy and birth rates after IVF were 45.8% and 33.3%,
      respectively and were not different among the 3 groups (P=0.59 and P=0.49). Four
      major complications during oocytes retrievals were observed in NS group, one in
      IS group and none in CS group. Presence of an inter-utero-rectal lesion at MRI
      decreased the rate of pregnancy (OR=0.49 [0.25, 0.97]). DISCUSSION AND
      CONCLUSIONS: Surgery for deep infiltrating endometriosis does not improve
      pregnancy and birth rates before IVF. This inter-utero-rectal extensive lesion
      might explain IVF failures by ovarian difficult access and difficulties in
      embryonic transfers. Further studies should explore the impact of surgical
      excision of inter-utero-rectal lesion on oocyte retrieval and embryonic transfer.

PMID- 25595946
TI  - Properties and functions of lactosylceramide from mouse neutrophils.
AB  - Lactosylceramide (LacCer), which is essential for many cellular processes, is
      highly expressed on the plasma membranes of human neutrophils and mediates innate
      immune functions. Less is known, however, about the properties and biological
      functions of LacCer in mouse neutrophils. This study therefore analyzed the
      properties of mouse neutrophil LacCer. LacCer was observed on the surface of
      these cells, with flow cytometry indicating that mouse neutrophil LacCer could be
      detected by the anti-LacCer mAb T5A7, but not by the anti-LacCer antibodies Huly
      m13 and MEM-74. The molecular species of LacCer were nearly identical in mouse
      and human neutrophils, including C24:0 and C24:1 fatty acid chain-containing
      species, although the LacCer content in plasma membranes was ~ 20-fold lower in
      mouse than in human neutrophils. Surface plasmon resonance analysis revealed that
      T5A7 bound to a lipid monolayer composed of LacCer, DOPC, cholesterol and
      sphingomyelin (molar ratio 0.1 : 10 : 10 : 1), whereas Huly-m13 did not. T5A7
      induced neutrophil migration, which was abolished by inhibitors of Src-family
      kinases, PI-3 kinases, and trimeric G (o/i) proteins. T5A7 also inhibited
      phagocytosis of non-opsonized zymosans by neutrophils. Taken together, these
      findings suggest that in mouse neutrophils, (i) LacCer is expressed as LacCer
      enriched microdomains in cell surface plasma membranes, (ii) these microdomains
      are recognized by T5A7 but not by other known anti-LacCer antibodies and (iii)
      LacCer is involved in cell migration and phagocytosis.

PMID- 25595948
TI  - 5,7-di-N-acetyl-acinetaminic acid: A novel non-2-ulosonic acid found in the
      capsule of an Acinetobacter baumannii isolate.
AB  - An Acinetobacter baumannii global clone 1 (GC1) isolate was found to carry a
      novel capsule biosynthesis gene cluster, designated KL12. KL12 contains genes
      predicted to be involved in the synthesis of simple sugars, as well as ones for N
      acetyl-L-fucosamine (L-FucpNAc) and N-acetyl-D-fucosamine (D-FucpNAc). It also
      contains a module of 10 genes, 6 of which are required for 5,7-di-N-acetyl
      legionaminic acid synthesis. Analysis of the composition of the capsule revealed
      the presence of N-acetyl-D-galactosamine, L-FucpNAc and D-FucpNAc, confirming the
      role of fnlABC and fnr/gdr genes in the synthesis of L-FucpNAc and D-FucpNAc,
      respectively. A non-2-ulosonic acid, shown to be 5,7-diacetamido-3,5,7,9
      tetradeoxy-L-glycero-L-altro-non-2-ulosonic acid, was also detected. This sugar
      has not previously been recovered from biological source, and was designated 5,7
      di-N-acetyl-acinetaminic acid (Aci5Ac7Ac). Proteins encoded by novel genes, named
      aciABCD, were predicted to be involved in the conversion of 5,7-di-N-acetyl
      legionaminic acid to Aci5Ac7Ac. A pathway for 5,7-di-N-acetyl-8-epilegionaminic
      acid biosynthesis was also proposed. In available A. baumannii genomes, genes for
      the synthesis of 5,7-di-N-acetyl-acinetaminic acid were only detected in two
      closely related capsule gene clusters, KL12 and KL13, which differ only in the
      wzy gene. KL12 and KL13 are carried by isolates belonging to clinically important
      clonal groups, GC1, GC2 and ST25. Genes for the synthesis of N-acyl derivatives
      of legionaminic acid were also found in 10 further A. baumannii capsule gene
      clusters, and three carried additional genes for production of 5,7-di-N-acetyl-8
      epilegionaminic acid.

PMID- 25595949
TI  - Alteration or adaptation, the two roads for human gastric mucin glycosylation
      infected by Helicobacter pylori.
AB  - Helicobacter pylori is a Gram-negative bacterium that colonizes the mucus niche
      of the gastric mucosa and infects more than half of the world's human population.
      Chronic infection may cause gastritis, duodenal ulcer, intestinal metaplasia or
      gastric cancer. In the stomach, H. pylori interacts with O-glycans of gastric
      mucins but the mechanism by which the bacteria succeed in altering the mucosa
      remains mainly unknown. To better understand the physiopathology of the
      infection, inhibitory adhesion assays were performed with various O-glycans
      expressed by human gastric mucins, and topographic expression of gastric mucins
      MUC5AC and MUC6 was analyzed for healthy uninfected individuals, for infected
      asymptomatic individuals and for patients infected by H. pylori and having the
      incomplete type of intestinal metaplasia. The glycosylation of the gastric mucosa
      of asymptomatic individuals infected by H. pylori was determined and compared
      with the glycosylation pattern found for patients with the incomplete type of
      intestinal metaplasia. Results show that H. pylori manages to modulate host's
      glycosylation during the course of infection in order to create a favorable
      niche, whereas asymptomatic infected individuals seem to counteract further steps
      of infection development by adapting their mucus glycosylation. 

PMID- 25595950
TI  - The state of oral anticoagulant therapy in patients with atrial fibrillation in
      Spain.

PMID- 25595947
TI  - Keeping track of the growing number of biological functions of chitin and its
      interaction partners in biomedical research.
AB  - Chitin is a vital polysaccharide component of protective structures in many
      eukaryotic organisms but seems absent in vertebrates. Chitin or chitin oligomers
      are therefore prime candidates for non-self-molecules, which are recognized and
      degraded by the vertebrate immune system. Despite the absence of polymeric chitin
      in vertebrates, chitinases and chitinase-like proteins (CLPs) are well conserved
      in vertebrate species. In many studies, these proteins have been found to be
      involved in immune regulation and in mediating the degradation of chitinous
      external protective structures of invading pathogens. Several important aspects
      of chitin immunostimulation have recently been uncovered, advancing our
      understanding of the complex regulatory mechanisms that chitin mediates.
      Likewise, the last few years have seen large advances in our understanding of the
      mechanisms and molecular interactions of chitinases and CLPs in relation to
      immune response regulation. It is becoming increasingly clear that their function
      in this context is not exclusive to chitin producing pathogens, but includes
      bacterial infections and cancer signaling as well. Here we provide an overview of
      the immune signaling properties of chitin and other closely related biomolecules.
      We also review the latest literature on chitinases and CLPs of the GH18 family.
      Finally, we examine the existing literature on zebrafish chitinases, and propose
      the use of zebrafish as a versatile model to complement the existing murine
      models. This could especially be of benefit to the exploration of the function of
      chitinases in infectious diseases using high-throughput approaches and
      pharmaceutical interventions. 

PMID- 25595952
TI  - Use of whole-genome sequencing for detection of the spread of VIM-4-producing
      Escherichia coli between two patients in Denmark.

PMID- 25595951
TI  - Rapid administration technique of ketamine for pediatric forearm fracture
      reduction: a dose-finding study.
AB  - STUDY OBJECTIVE: We estimate the minimum dose and total sedation time of rapidly
      infused ketamine that achieves 3 to 5 minutes of effective sedation in children
      undergoing forearm fracture reduction in the emergency department. METHODS: We
      used the up-down method to estimate the median dose of intravenous ketamine
      infused during less than or equal to 5 seconds that provided effective sedation
      in 50% (ED50) and 95% (ED95) of healthy children aged 2 to 5, 6 to 11, or 12 to
      17 years who were undergoing forearm fracture reduction. Most patients were
      pretreated with opioids. Three investigators blinded to ketamine dose
      independently graded sedation effectiveness by viewing a video recording of the
      first 5 minutes of sedation. Recovery was assessed by modified Aldrete score.
      RESULTS: We enrolled 20 children in each age group. The estimated ED50 was 0.7,
      0.5, and 0.6 mg/kg and the estimated ED95 was 0.7, 0.7, and 0.8 mg/kg for the
      groups aged 2 to 5, 6 to 11, and 12 to 17 years, respectively. For the group aged
      2 to 5 years, an empirically derived ED95 was 0.8 mg/kg. All patients who
      received the empirically derived ED95 in the group aged 2 to 5 years or the
      estimated ED95 in the groups aged 6 to 11 and 12 to 17 years had effective
      sedation. The median total sedation time for the 3 age groups, respectively, was
      25, 22.5, and 25 minutes if 1 dose of ketamine was administered and 35, 25, and
      45 minutes if additional doses were administered. No participant experienced
      serious adverse events. CONCLUSION: We estimated ED50 and ED95 for rapidly
      infused ketamine for 3 age groups undergoing fracture reduction. Total sedation
      time was shorter than that in most previous studies.

PMID- 25595953
TI  - Erratum to: postural adjustment errors during lateral step initiation in older
      and younger adults.

PMID- 25595954
TI  - A 3-month intervention of Dance Dance Revolution improves interference control in
      elderly females: a preliminary investigation.
AB  - Exercise regimens suitable to the elderly remain under investigated; therefore,
      this study examined the effects of Dance Dance Revolution (DDR) on cognitive
      control in elderly females. Twenty-six healthy elderly females leading a
      sedentary lifestyle were assigned to a DDR, brisk walking, or control group.
      Participants in the DDR and brisk walking groups engaged in moderate physical
      exercise three times per week for 3 months, whereas the control group maintained
      a sedentary lifestyle. Each participant performed a flanker task before and after
      the intervention. The results revealed that both DDR and brisk walking shortened
      reaction time, N2 latency, and P3 latency relative to those of the control group.
      These findings suggest that DDR intervention is as effective as that of brisk
      walking in improving inhibitory control for elderly people. Therefore, DDR can be
      used as a viable alternative exercise to enhance cognitive function for the
      elderly and motivate individuals who are less willing to be active.

PMID- 25595955
TI  - Staying Well: A Follow Up of a 5-Week Mindfulness Based Stress Reduction
      Programme for a Range of Psychological Issues.
AB  - 112 women and 37 men, with an average age of 50 years were referred for MBSR
      training with a range of chronic psychological issues. All participants completed
      the Warwick-Edinburgh Mental Wellbeing Scale (Tennant et al. in Health and
      Quality of Life Outcomes 5:63, 2007) before and after the mindfulness training
      programme. A significant overall effect of pre/post training was found and this
      difference was not related to a specific disorder. The results suggest that a
      'brief' dose of MBSR can have a positive impact on measures of well-being in a
      manner that is not related to patient characteristics. A follow-up of 28
      participants confirms that participation in the 5-week Living Mindfully MBSR
      programme significantly enhances psychological well-being immediately after
      training, and this benefit is maintained up to 4 years after training. Continued
      practice in mindfulness meditation showed an insignificant relationship to well
      being scores at follow up. Qualitative data suggest that the 5 week MBSR is an
      effective means of developing emotion regulation and psychological well-being.

PMID- 25595956
TI  - The role of evidence based medicine in neurotrauma.
AB  - The introduction of evidence based medicine de-emphasised clinical experience and
      so-called "background information" and stressed the importance of evidence gained
      from clinical research when making clinical decisions. For many years randomised
      controlled trials have been seen to be the only way to advance clinical practice,
      however, applying this methodology in the context of severe trauma can be
      problematic. In addition, it is increasingly recognised that considerable
      clinical experience is required in order to critically evaluate the quality of
      the evidence and the validity of the conclusions as presented. A contemporary
      example is seen when considering the role of decompressive craniectomy in the
      management of neurotrauma. Although there is a considerable amount of evidence
      available attesting to the efficacy of the procedure, considerable clinical
      expertise is required in order to properly interpret the results of these studies
      and the implications for clinical practice. Given these limitations the time may
      have come for a redesign of the traditional pyramid of evidence, to a model that
      re-emphasises the importance of "background information" such as pathophysiology
      and acknowledges the role of clinical experience such that the evidence can be
      critically evaluated in its appropriate context and the subsequent implications
      for clinical practice be clearly and objectively defined. 

PMID- 25595957
TI  - Clinical characteristics and diagnostic imaging of cranial osteoblastoma.
AB  - Benign osteoblastoma is a rare, vascular, osteoid-forming bone tumor that occurs
      even less frequently in the cranial bones. Benign osteoblastoma of the cranium
      affects women slightly more often than men and typically presents in the first
      three decades of life. Although clinical presentation can vary depending on
      location, cranial osteoblastoma usually presents as a painful, non-mobile,
      subcutaneous mass or swelling. On CT scan, it generally presents as a well
      demarcated, mixed lytic and sclerotic lesion, with enlarged diploe, thinning
      outer and/or inner tables, and varying degrees of calcification. It is hypo to
      isointense on T1-weighted MRI and has variable presentation on T2-weighted MRI.
      Gross total resection is the definitive treatment, while subtotal resection is
      utilized when it is necessary to preserve critical adjacent neurovascular
      structures. 

PMID- 25595958
TI  - A novel mutation in GJB1 (c.212T>G) in a Chinese family with X-linked Charcot
      Marie-Tooth disease.
AB  - Gap junction protein beta 1 (GJB1) gene mutations lead to X-linked Charcot-Marie
      Tooth (CMTX) disease. We investigated a Chinese family with CMTX and identified a
      novel GJB1 point mutation. Clinical and electrophysiological features of the
      pedigree were examined, and sequence alterations of the coding region of GJB1
      that encode connexin32 were determined by direct sequencing. Sequence alignment
      of the mutation site was performed using Clustal W. Mutation effects were
      analysed using PolyPhen-2, SIFT and Mutation Taster software. The three
      dimensional structures of the mutant and wild-type proteins were predicted by
      modeling with SWISS MODEL online software. The affected family members displayed
      typical Charcot-Marie-Tooth phenotypes, but phenotypic heterogeneity was
      observed. Nerve conduction velocities of all affected patients were slow.
      Sequencing of GJB1 revealed a heterozygous T>G missense mutation at nucleotide
      212 in the proband, the proband's mother and the proband's daughter. The affected
      male sibling of the proband displayed a hemizygous missense mutation with T>G
      transition at the identical position on the GJB1 gene. This mutation resulted in
      an amino acid change from isoleucine to serine that was predicted to lead to
      tertiary structural alterations that would disrupt the function of the GJB1
      protein. A novel point mutation in GJB1 was detected, expanding the spectrum of
      GJB1 mutations known to be associated with CMTX. 

PMID- 25595959
TI  - National data on stroke outcomes in Thailand.
AB  - Stroke is a major public health problem worldwide. There are limited data on
      national stroke prevalence and outcomes after the beginning of the thrombolytic
      therapy era in Thailand. This study aimed to investigate the prevalence and
      factors associated with mortality in stroke patients in Thailand using the
      national reimbursement databases. Clinical data retrieved included individuals
      under the universal coverage, social security, and civil servant benefit systems
      between 1 October 2009 and 30 September 2010. The stroke diagnosis code was based
      on the International Classification of Diseases 10th revision system including
      G45 (transient cerebral ischemic attacks and related syndromes), I61
      (intracerebral hemorrhage), and I63 (cerebral infarction). The prevalence and
      stroke outcomes were calculated from these coded data. Factors associated with
      death were evaluated by multivariable logistic regression analysis. We found that
      the most frequent stroke subtype was cerebral infarction with a prevalence of 122
      patients per 100,000 of population, an average length of hospital stay of 6.8
      days, an average hospital charge of 20,740 baht (~$USD 691), a mortality rate of
      7%, and thrombolytic prescriptions of 1%. The significant factors associated with
      stroke mortality were septicemia, pulmonary embolism, pneumonia, myocardial
      infarction, status epilepticus, and heart failure. In conclusion, the prevalence
      and outcomes of stroke in Thailand were comparable with other countries. The era
      of thrombolytic therapy has just begun in Thailand.

PMID- 25595960
TI  - Sex differences in cognition among Chinese people with Parkinson's disease.
AB  - To investigate sex differences in cognitive function in Parkinson's disease
      patients, a cohort of 172 male patients and 139 female patients were recruited
      for this study. Their demographic and clinical features, including age, disease
      duration, education level, Unified Parkinson's Disease Rating Scale-III, Hoehn
      Yahr Scale, activities of daily living, Hamilton Depression Rating Scale and
      Hamilton Anxiety Rating Scale score were recorded. The Mini Mental State
      Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult
      Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese
      Revision (WMS-RC) scores were compared to distinguish the cognitive properties
      between the two groups. The MMSE values did not show a significant difference
      between the groups. However, the MoCA scores of male patients were significantly
      higher than those of female patients (adjusted p<0.05). The male group
      demonstrated better performances with respect to visuospatial function, naming
      and abstraction (adjusted p<0.05). The WAIS-RC data showed that female patients
      had lower scores in information, vocabulary, picture completion, block design and
      picture arrangement (adjusted p<0.05), and the WMS-RC data showed that 100-1 and
      cumulative addition abilities were significantly weaker in females than males
      (adjusted p<0.05). Cognitive disturbances were more prevalent and severe in women
      among Chinese Parkinson's disease patients. 

PMID- 25595962
TI  - Single-balloon versus double-balloon bipedicular kyphoplasty for osteoporotic
      vertebral compression fractures.
AB  - Twenty-eight patients with osteoporotic vertebral compression fractures (OVCF)
      were treated with single-balloon bipedicular kyphoplasty (Group A), and 40
      patients were treated with double-balloon bipedicular kyphoplasty (Group B).
      Visual Analogue Scale (VAS) score, vertebral height, and kyphotic angle (KA) were
      evaluated pre-operatively, post-operatively (3 days after surgery) and at final
      follow-up. Operative time, X-ray exposure frequency and costs were recorded. The
      mean operative time and X-ray exposure frequency in Group A were greater than in
      Group B (p<0.05). Significant improvement of the VAS score was noted in each
      group, and remained unchanged at final follow-up. Mean increases of anterior and
      middle height of the fractured vertebral body were 5.14mm and 4.14mm in Group A,
      respectively, and 6.22mm and 5.06mm in Group B, respectively, and the differences
      between the groups were statistically significant (p<0.05). Mean reduction of KA
      was 6.9 degrees  in Group A and 8.8 degrees  in Group B, which was statistically
      significant (p<0.05). No statistically significant difference was observed in
      terms of cement leakage between groups. The mean cost of Group A (US$4202) was
      significantly less than that of Group B (US$6220) (p<0.001). Single-balloon
      bipedicular kyphoplasty is a safe and cost-effective surgical method for the
      treatment of OVCF. It can achieve pain relief comparable with double-balloon
      bipedicular kyphoplasty. However, double-balloon bipedicular kyphoplasty is more
      efficacious in terms of the restoration of vertebral height and reduction of KA,
      and the operative time and X-ray exposure frequency are lower.

PMID- 25595961
TI  - Association between hemoglobin A1C levels and clinical outcome in ischemic stroke
      patients with or without diabetes.
AB  - Individuals with diabetes are at a higher risk of suffering stroke, but whether
      chronic hyperglycemia affects clinical outcomes after stroke is unclear. We
      examined whether chronic hyperglycemia, measured in terms of hemoglobin A1C
      (HbA1C) levels, influences clinical outcomes after acute ischemic stroke. We
      prospectively and consecutively included patients admitted within 7 days of
      ischemic stroke onset. Demographic and clinical information and outcomes were
      analyzed separately for patients with or without diabetes in order to identify
      associations with HbA1C tercile. A total of 1351 patients without diabetes and
      526 with diabetes were included. The risk of mortality and poor outcome showed a
      tendency to increase with increasing HbA1C tercile in both groups. Rates of
      mortality and poor outcome were significantly higher in the third tercile than in
      the first tercile. In contrast, rates of mortality and poor outcome in the second
      tercile were not significantly different from those in the first tercile. The
      adjusted odds ratios of poor outcome and mortality increased with increasing
      tercile of HbA1C both in patients with diabetes and in patients without diabetes,
      and these relationships were independent of other confounders. Kaplan-Meier
      estimates of cumulative mortality also increased with increasing HbA1C in both
      groups of patients (with diabetes, p=0.034; without diabetes, p=0.025). Our
      results suggest that elevated HbA1C is associated with risk of poor outcome and
      mortality in ischemic stroke patients with or without diabetes.

PMID- 25595963
TI  - Outcome of salvage treatment for recurrent glioblastoma.
AB  - Most glioblastoma (GBM) cases recur within a year and almost all cases recur at
      some point. Standard treatment for recurrent GBM has not yet been established. We
      investigated the outcome of various salvage treatments for recurrent GBM.
      Retrospective analysis was undertaken in 144 patients who received salvage
      treatment at the time of first progression after maximum debulking surgery
      followed by concomitant chemoradiotherapy and adjuvant temozolomide (TMZ)
      chemotherapy. The median follow-up period was 18.2 months. We grouped these
      patients into five groups according to the salvage modalities: Gamma Knife
      radiosurgery (GKS) group (n=29), TMZ group (n=31), GKS+TMZ group (n=28),
      reoperation group (n=38) and "other treatment" group (n=18). The median time to
      first progression from initial diagnosis was 8.8 months. The median overall
      survival (OS) of the five different treatment groups; GKS, TMZ, GKS+TMZ,
      reoperation, and "other treatment", was 9.2, 5.6, 15.5, 13.2, and 8.0 months,
      respectively. Median progression-free survival (PFS) was 3.6, 2.3, 6.0, 4.3, and
      2.6 months, respectively. Pairwise comparison of OS of the GKS+TMZ group with the
      other groups showed that the OS of the GKS+TMZ group was significantly better
      than all others except the reoperation group. Statistically significant
      prolongation of PFS was observed in the GKS+TMZ group compared with the TMZ group
      and the "other treatment" group. GKS followed by TMZ salvage treatment was a good
      prognostic factor for both PFS and OS in multivariate analysis. Retrospectively,
      GKS+TMZ as a salvage treatment, tended to provide a superior survival benefit at
      the time of recurrence.

PMID- 25595965
TI  - Cervical Cancer Screening Knowledge and Behavior among Women Attending an Urban
      HIV Clinic in Western Kenya.
AB  - Cervical cancer is a highly preventable disease that disproportionately affects
      women in developing countries and women with HIV. As integrated HIV and cervical
      cancer screening programs in Sub-Saharan Africa mature, we have an opportunity to
      measure the impact of outreach and education efforts and identify areas for
      future improvement. We conducted a cross-sectional survey of 106 women enrolled
      in care at an integrated HIV clinic in the Nyanza Province of Kenya 5 years after
      the start of a cervical cancer screening program. Female clinic attendees who met
      clinic criteria for cervical cancer screening were asked to complete an oral
      questionnaire assessing their cervical cancer knowledge, attitudes, and screening
      history. Ninety-nine percent of women had heard of screening, 70 % felt at risk,
      and 84 % had been screened. Increased duration of HIV diagnosis was associated
      with feeling at risk and with a screening history. Nearly half (48 %) of women
      said they would not get screened if they had to pay for it.

PMID- 25595964
TI  - Spatial distributions of AQP5 and AQP0 in embryonic and postnatal mouse lens
      development.
AB  - The expression of the water channel protein aquaporin (AQP)-5 in adult rodent and
      human lenses was recently reported using immunohistochemistry, molecular biology,
      and mass spectrometry techniques, confirming a second transmembrane water channel
      that is present in lens fibre cells in addition to the abundant AQP0 protein.
      Interestingly, the sub-cellular distribution and level of post-translational
      modification of both proteins changes with fibre cell differentiation and
      location in the adult rodent lens. This study compares the sub-cellular
      distribution of AQP0 and AQP5 during embryonic and postnatal fibre cell
      development in the mouse lens to understand how the immunolabelling patterns for
      both AQPs observed in adult lens are first established. Immunohistochemistry was
      used to map the cellular and sub-cellular distribution of AQP5 and AQP0
      throughout the lens in cryosections from adult (6 weeks-8 months) and postnatal
      (0-2 weeks) mouse lenses and in sections from paraffin embedded mouse embryos
      (E10-E19). All sections were imaged by fluorescence confocal microscopy. Using
      antibodies directed against the C-terminus of each AQP, AQP5 was abundantly
      expressed early in development, being found in the cytoplasm of cells of the lens
      vesicle and surrounding tissues (E10), while AQP0 was detected later (E11), and
      only in the membranes of elongating primary fibre cells. During the course of
      subsequent embryonic and postnatal development the pattern of cytoplasmic AQP5
      and membranous AQP0 labelling was maintained until postnatal day 6 (P6). From P6
      AQP5 labelling became progressively more membranous initially in the lens nucleus
      and then later in all regions of the lens, while AQP0 labelling was abruptly lost
      in the lens nucleus due to C-terminal truncation. Our results show that the
      spatial distribution patterns of AQP0 and AQP5 observed in the adult lens are
      established during a narrow window of postnatal development (P6-P15) that
      precedes eye opening and coincides with regression of the hyaloid vascular
      system. Our results support the hypothesis that, in the older fibre cells,
      insertion of AQP5 into the fibre cell membrane may compensate for any change in
      the functionality of AQP0 induced by truncation of its C-terminal tail. 

PMID- 25595966
TI  - The invisible addiction: cell-phone activities and addiction among male and
      female college students.
AB  - BACKGROUND AND AIMS: The primary objective of the present study was to
      investigate which cell-phone activities are associated with cell-phone addiction.
      No research to date has studied the full-range of cell-phone activities, and
      their relationship to cell-phone addiction, across male and female cell-phone
      users. METHODS: College undergraduates (N = 164) participated in an online
      survey. Participants completed the questionnaire as part of their class
      requirements. The questionnaire took 10 and 15 minutes to complete and contained
      a measure of cell-phone addiction and questions that asked how much time
      participants spent daily on 24 cell-phone activities. RESULTS: Findings revealed
      cell-phone activities that are associated significantly with cell-phone addiction
      (e.g., Instagram, Pinterest), as well as activities that one might logically
      assume would be associated with this form of addiction but are not (e.g.,
      Internet use and Gaming). Cell-phone activities that drive cell-phone addiction
      (CPA) were found to vary considerably across male and female cell-phone users.
      Although a strong social component drove CPA for both males and females, the
      specific activities associated with CPA differed markedly. CONCLUSIONS: CPA
      amongst the total sample is largely driven by a desire to connect socially. The
      activities found to be associated with CPA, however, differed across the sexes.
      As the functionality of cell-phones continues to expand, addiction to this
      seemingly indispensable piece of technology becomes an increasingly realistic
      possibility. Future research must identify the activities that push cell-phone
      use beyond its "tipping point" where it crosses the line from a helpful tool to
      one that undermines our personal well-being and that of others.

PMID- 25595968
TI  - Delayed signal transmission in area 17, area 18 and the posteromedial lateral
      suprasylvian area of aged cats.
AB  - To investigate the effect of senescence on signal transmission, we have compared
      the visual response latency and spontaneous activity of cells in the lateral
      geniculate nucleus (LGN), area 17, area 18 and posteromedial lateral suprasylvian
      area (PMLS) of young and old cats. We found that LGN cells in old cats exhibit
      largely normal visual response latency. In contrast, all the other three areas
      exhibited significant aging-related delays in the visual response latency. On
      average, PMLS showed most pronounced delays among these three areas. Area 18
      slowed more than area 17, but this was not significant. The degradation of signal
      timing in the visual cortex might provide insight into neuronal response
      mechanism underlying perception slowing during aging. 

PMID- 25595967
TI  - Early activation of microglia and astrocytes in mouse models of spinocerebellar
      ataxia type 1.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an incurable, dominantly inherited
      neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat
      expansion in the protein ataxin-1 (ATXN1). While analysis of human autopsy
      material indicates significant glial pathology in SCA1, previous research has
      focused on characterizing neuronal dysfunction. In this study, we characterized
      astrocytic and microglial response in SCA1 using a comprehensive array of mouse
      models. We have discovered that astrocytes and microglia are activated very early
      in SCA1 pathogenesis even when mutant ATXN1 expression was limited to Purkinje
      neurons. Glial activation occurred in the absence of neuronal death, suggesting
      that glial activation results from signals emanating from dysfunctional neurons.
      Finally, in all different models examined glial activation closely correlated
      with disease progression, supporting the development of glial-based biomarkers to
      follow disease progression. 

PMID- 25595969
TI  - Developmental decline in modulation of glutamatergic synapses in layer IV of the
      barrel cortex by group II metabotropic glutamate receptors.
AB  - Previously, we demonstrated that group II metabotropic glutamate receptors
      (mGluRs) reduce glutamate release from thalamocortical synapses during early
      postnatal development (P7-11). To further examine the role of group II mGluRs in
      the modulation of somatosensory circuitry, we determined whether group II mGluRs
      continue to modulate thalamocortical synapses until adulthood and whether these
      receptors also modulate intra-cortical synapses in the barrel cortex. To address
      these issues, we examined the effect of the group II mGluR agonists on
      thalamocortical excitatory postsynaptic currents (EPSCs) and intra-barrel EPSCs
      in slices from animals of different ages (P7-53). We found that the depression of
      thalamocortical EPSCs by group II mGluRs rapidly declined after the second
      postnatal week. In contrast, adenosine continued to depress thalamocortical EPSCs
      via a presynaptic mechanism in young adult mice (P30-50). Activation of group II
      mGluRs also reduced intra-barrel EPSCs through a postsynaptic mechanism in young
      mice (P7-11). Similar to the thalamocortical synapses, the group II mGluR
      modulation of intra-barrel excitatory synapses declined with development. In
      young adult animals (P30-50), group II mGluR stimulation had little effect on
      intra-barrel EPSCs but did hyperpolarize the neurons. Together our results
      demonstrate that group II mGluRs modulate barrel cortex circuitry by presynaptic
      and postsynaptic mechanisms depending on the source of the synapse and that this
      modulation declines with development.

PMID- 25595970
TI  - Fibroblast growth factor and endothelin-1 receptors mediate the response of human
      striatal precursor cells to hypoxia.
AB  - Fetal striatal transplantation has emerged as a new therapeutic strategy in
      Huntington's disease (HD). Hypoxia is one of the microenvironmental stress
      conditions to which fetal tissue is exposed as soon as it is isolated and
      transplanted into the diseased host brain. Mechanisms that support neuroblast
      survival and replenishment of damaged cells within the HD brain in the hypoxic
      condition have yet to be fully elucidated. This study is aimed at investigating
      the molecular pathways associated with the hypoxic condition in human fetal
      striatal neuroblasts (human striatal precursor (HSP) cells), using the hypoxia
      mimetic agent cobalt chloride (CoCl2). We analyzed the effect of CoCl2 on HSP
      cell proliferation and on the expression of hypoxia-related proteins, such as
      hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor
      (VEGF). Moreover, we evaluated fibroblast growth factor 2 (FGF2; 50ng/ml) and
      endothelin-1 (ET-1; 100nM) proliferative/survival effects in HSP cells in
      normoxic and hypoxic conditions. Dose-response experiments using increasing
      concentrations of CoCl2 (50-750MUM) showed that the HSP cell growth was
      unaffected after 24h, while it increased at 48h, with the maximal effect observed
      at 400MUM. In contrast, cell survival was impaired at 72h. Hypoxic conditions
      determined HIF-1alpha protein accumulation and increased gene and protein
      expression of VEGF, while FGF2 and ET-1 significantly stimulated HSP cell
      proliferation both in normoxic and hypoxic conditions, thus counteracting the
      apoptotic CoCl2 effect at 72h. The incubation with selective receptor (FGFR1,
      endothelin receptor A (ETA) and endothelin receptor B (ETB)) inhibitors abolished
      the FGF2 and ET-1 neuroprotective effect. In particular, ET-1 stimulated HSP cell
      survival through ETA in normoxic conditions and through ETB during hypoxia.
      Accordingly, ETA expression was down-regulated, while ETB expression was up
      regulated by CoCl2 treatment. Overall, our results support the idea that HSP
      cells possess the machinery for their adaptation to hypoxic conditions and that
      neurotrophic factors, such as FGF2 and ET-1, may sustain neurogenesis and long
      term survival through complex receptor-mediated mechanisms. 

PMID- 25595971
TI  - Persistent increases in rat hypothalamic POMC gene expression following chronic
      withdrawal from chronic "binge" pattern escalating-dose, but not steady-dose,
      cocaine.
AB  - Recent research suggests an involvement of pro-opiomelanocortin (POMC) gene
      products (e.g., beta-endorphin) in modulating cocaine-induced reward and
      addiction-like behaviors in rodents. In this study, we investigated whether
      chronic "binge" cocaine and its withdrawal altered POMC gene expression in the
      brain of rats. Male Fischer rats were treated with two different chronic (14-day)
      "binge" pattern cocaine administration regimens (three injections at 1-h
      intervals, i.p.): steady-dose (45mg/kg/day) and escalating-dose (90mg/kg on the
      last day). Although there was no POMC mRNA alteration after chronic steady-dose
      cocaine, a significant decrease in POMC mRNA levels in the hypothalamus was found
      after chronic escalating-dose cocaine. In contrast, after acute (1-day)
      withdrawal from chronic "binge" escalating-dose regimen, but not steady-dose
      regimen, there were increased hypothalamic POMC mRNA levels that persisted into
      14days of protracted withdrawal. To study the role of the endogenous opioid
      systems in the cocaine withdrawal effects, we administered a single naloxone
      injection (1mg/kg) that caused elevated POMC mRNA levels observed 24h later in
      cocaine naive rats, but it did not lead to further increases in cocaine-withdrawn
      rats. Our results suggest that during withdrawal from chronic "binge" escalating
      dose cocaine: (1) there was a persistent increase in hypothalamic POMC gene
      expression; and (2) hyposensitivity of the POMC gene expression to naloxone
      indicates altered opioidergic tone at or above the hypothalamic level. 

PMID- 25595972
TI  - Functional connectivity among brain networks in continuous feedback of finger
      force.
AB  - Motor feedback usually engages distinct sensory and cognitive processes based on
      different feedback conditions, e.g., the real and sham feedbacks. It was thought
      that these processes may rely on the functional connectivity among the brain
      networks. However, it remains unclear whether there is a difference in the
      network connectivity between the two feedback conditions. To address this issue,
      we carried out a functional magnetic resonance imaging (fMRI) study by employing
      a new paradigm, i.e., continuous feedback (8min) of finger force. Using
      independent component analysis and functional connectivity analysis, we found
      that as compared with the sham feedback, the real feedback recruited stronger
      negative connectivity between the executive network (EN) and the posterior
      default mode network (pDMN). More intriguingly, the left frontal parietal network
      (lFPN) exhibits positive connectivity with the pDMN in the real feedback while in
      the sham feedback, the lFPN shows connectivity with the EN. These results suggest
      that the connectivity among EN, pDMN, lFPN could differ depending on the real and
      sham feedbacks, and the lFPN may balance the competition between the pDMN and EN,
      thus supporting the sensory and cognitive processes of the motor feedback. 

PMID- 25595973
TI  - Astrocytes in physiological aging and Alzheimer's disease.
AB  - Astrocytes are fundamental for homoeostasis, defence and regeneration of the
      central nervous system. Loss of astroglial function and astroglial reactivity
      contributes to the aging of the brain and to neurodegenerative diseases. Changes
      in astroglia in aging and neurodegeneration are highly heterogeneous and region
      specific. In animal models of Alzheimer's disease (AD) astrocytes undergo
      degeneration and atrophy at the early stages of pathological progression, which
      possibly may alter the homeostatic reserve of the brain and contribute to early
      cognitive deficits. At later stages of AD reactive astrocytes are associated with
      neurite plaques, the feature commonly found in animal models and in human
      diseased tissue. In animal models of the AD reactive astrogliosis develops in
      some (e.g. in the hippocampus) but not in all regions of the brain. For instance,
      in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to
      emerging beta-amyloid deposits. These deficits in reactivity coincide with higher
      vulnerability of these regions to AD-type pathology. Astroglial morphology and
      function can be regulated through environmental stimulation and/or medication
      suggesting that astrocytes can be regarded as a target for therapies aimed at the
      prevention and cure of neurodegenerative disorders. 

PMID- 25595974
TI  - Activation of NF-kappaB signaling pathway in HSV-1-induced mouse facial palsy:
      Possible relation to therapeutic effect of glucocorticoids.
AB  - It has been documented that infection of herpes simplex virus type 1 (HSV-1)
      contributes to the initiation of Bell's palsy. However, the exact mechanisms
      responsible for this disorder have not been fully elucidated to date. A mouse
      model of facial palsy induced by HSV-1 provides an opportunity to investigate the
      alteration in activities of nuclear factor-kappa B (NF-kappaB) and its consequent
      effect on two key inflammatory factors, i.e., tumor necrosis factor (TNF)-alpha
      and cyclooxygenase-2 (COX-2), as well as the effect of glucocorticoids (GCs) in
      this work. I-kappa B (IkappaB)-alpha phosphorylation and NF-kappaB nuclear
      translocation were measured by western blotting, and NF-kappaB/DNA binding
      activity was assessed by electrophoretic mobility shift assay (EMSA). Results
      showed the IkappaB-alpha phosphorylation and degradation as well as NF-kappaB
      activation in a time-dependent manner. The expression of TNF-alpha and COX-2 were
      determined by real-time polymerase chain reaction (PCR), western blotting and/or
      enzyme-linked immunosorbent assay (ELISA) respectively. Concomitant with the
      activation, the expression and secretion of TNF-alpha and COX-2 were rapidly
      induced in HSV-1-infected paralyzed mice. Conversely, the activation of NF-kappaB
      and up-regulation of TNF-alpha and COX-2 were blocked by pretreatment with NF
      kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) before being inoculated with
      HSV-1 to mice. In addition, GCs inhibited the nuclear translocation and DNA
      binding activity of NF-kappaB via inhibiting IkappaB-alpha degradation.
      Meanwhile, TNF-alpha production and COX-2 expression were significantly reduced
      by GCs. In conclusion, HSV-1 inoculation induced the activation of NF-kappaB,
      expression and secretion of TNF-alpha and COX-2 in the facial paralyzed mice,
      while, glucocorticoid effectively down-regulated TNF-alpha and COX-2 expression
      in HSV-1-induced paralyzed mice. 

PMID- 25595975
TI  - The effect of chronic corticosterone on fear learning and memory depends on dose
      and the testing protocol.
AB  - Chronic exposure to the stress hormone corticosterone (CORT) is known to alter
      plasticity within hippocampal and amygdalar circuits that mediate fear learning
      and memory. The purpose of this experiment was to clarify the effects of chronic
      CORT on Pavlovian fear conditioning, which is dependent on intact hippocampal and
      amygdalar activity. In particular, we assessed whether the effect of chronic CORT
      on fear learning and memory is influenced by two factors-the dose of CORT and the
      order in which rats are tested for freezing to context versus tone cues. Male
      Long-Evans rats received low-dose CORT (5mg/kg), high-dose CORT (40mg/kg), or
      vehicle injections once daily for 21days. On day 22, the rats were trained in a
      fear-conditioning paradigm. On days 23 and 24, the rats were tested for the
      retrieval of fear memories to context and tone cues in a counterbalanced way-half
      the rats received context testing on day 23 and then tone testing on day 24 and
      half the rats received tone testing on day 23 followed by context testing on day
      24. Our results revealed dose-dependent effects of CORT on memory retrieval: Rats
      injected with high-dose CORT froze significantly more than control rats to both
      context and tone cues regardless of what testing day these cues were presented.
      However, rats injected with low-dose CORT froze significantly more than control
      rats to tone cues only. We also found an order effect in that the effects of CORT
      on freezing were greater on the second day of testing, regardless of whether that
      testing was to context or tones cues. This order effect may be due to a lack of
      extinction in the CORT rats. Overall, these results suggest a relationship
      between stress intensity and testing conditions that should be taken into account
      when assessing the effect of stress on fear memories. 

PMID- 25595976
TI  - Structural changes in the CNS of patients with hemifacial spasm.
AB  - Hemifacial spasm (HFS) is a peripheral nerve disorder which impacts the living
      quality of patients both psychologically and physically. Whether HFS has
      structural changes under these specific stressors including psychological and
      physiological conditions in the CNS remains largely unknown. In the current
      study, voxel-based morphometry (VBM) was used to evaluate changes in gray matter
      (GM) by using T1-weighted imaging in 25 HFS patients and 25 demographically
      similar healthy volunteers. The severity of the spasm was assessed using a Cohen
      evaluation scale. Hamilton anxiety (HAMA) and Hamilton depression (HAMD) rating
      scales were used to evaluate the affective conditions of subjects. 3D-FIESTA and
      3D-TOF sequences were applied to evaluate the neurovascular compression (NVC)
      rating in each subject. In our results, we found that HFS patients had higher NVC
      rating scores than those of healthy volunteers, and the spasm severity rating was
      positively correlated with the NVC rating (r=0.736, p<0.001). HFS patients had
      higher scores on the HAMA and HAMD compared with healthy volunteers. For the GM
      comparison, reductions were found in the thalamus, putamen, pallidum,
      dorsolateral prefrontal cortex, amygdala and parahippocampal gyrus in patients
      with HFS compared with healthy volunteers. Additionally, the GM volume changes in
      the amygdala did not exhibit any significant between-group differences with HAMA
      and HAMD scores as covariates. Our results suggested that HFS probably led to GM
      volume abnormalities of the CNS. We indicated that the GM volume changes of the
      amygdala may be highly related to emotional factors. 

PMID- 25595977
TI  - Alterations of orexinergic and melanin-concentrating hormone neurons in
      experimental sleeping sickness.
AB  - Human African trypanosomiasis or sleeping sickness is a severe, neglected
      tropical disease caused by the extracellular parasite Trypanosoma brucei. The
      disease, which leads to chronic neuroinflammation, is characterized by sleep and
      wake disturbances, documented also in rodent models. In rats and mice infected
      with Trypanosoma brucei brucei, we here tested the hypothesis that the disease
      could target neurons of the lateral hypothalamus (LH) containing orexin (OX)-A or
      melanin-concentrating hormone (MCH), implicated in sleep/wake regulation. In the
      cerebrospinal fluid of infected rats, the OX-A level was significantly decreased
      early after parasite neuroinvasion, and returned to the control level at an
      advanced disease stage. The number of immunohistochemically characterized OX-A
      and MCH neurons decreased significantly in infected rats during disease
      progression and in infected mice at an advanced disease stage. A marked reduction
      of the complexity of dendritic arborizations of OX-A neurons was documented in
      infected mice. The evaluation of NeuN-immunoreactive neurons did not reveal
      significant neuronal loss in the LH of infected mice, thus suggesting a potential
      selective vulnerability of OX-A and MCH neurons. Immunophenotyping and
      quantitative analysis showed in infected mice marked activation of microglial
      cells surrounding OX-A neurons. Day/night oscillation of c-Fos baseline
      expression was used as marker of OX-A neuron activity in mice. In control animals
      Fos was expressed in a higher proportion of OX-A neurons in the night (activity)
      phase than in the day (rest) phase. Interestingly, in infected mice the diurnal
      spontaneous Fos oscillation was reversed, with a proportion of OX-A/Fos neurons
      significantly higher at daytime than at nighttime. Altogether the findings reveal
      a progressive decrease of OX-A and MCH neurons and dysregulation of OX-A neuron
      diurnal activity in rodent models of sleeping sickness. The data point to the
      involvement of these peptidergic neurons in the pathogenesis of sleep/wake
      alterations in the disease and to their vulnerability to inflammatory signaling. 

PMID- 25595978
TI  - Inhibition of the small GTPase Cdc42 in regulation of epileptic-seizure in rats.
AB  - Altered expression of neuronal cytoskeletal proteins are known to play an
      important role in hyper-excitability of neurons in patients and animal models of
      epilepsy. Our previous work showed that cell division cycle 42 GTP-binding
      protein (Cdc42), a small GTPase of the Rho-subfamily, is significantly increased
      in the brain tissue of patients with temporal lobe epilepsy (TLE) and in the
      brain tissues of the epileptic model of rats. However, whether inhibition of
      Cdc42 can modify epileptic seizures has not been investigated. In this study,
      using a pilocarpine-induced epileptic model, we found that pretreatment with
      ML141, a specific inhibitor of Cdc42, reduces seizure severity. Whole-cell patch
      clamp recording on CA1 pyramidal neurons in hippocampal slices from pilocarpine
      induced epileptic model demonstrated that ML141 significantly inhibits the
      frequency of action potentials (APs), increases the amplitude and frequency of
      miniature inhibitory postsynaptic currents (mIPSCs), and increases the amplitude
      of evoked inhibitory postsynaptic currents (eIPSCs). However, ML141 did not have
      an impact on the miniature excitatory postsynaptic currents (mEPSCs). Our results
      are the first to indicate that Cdc42 plays an important role in the onset and
      progression of epileptic-seizures by regulating synaptic inhibition. 

PMID- 25595979
TI  - Brain hemodynamic response to somatosensory stimulation in Neuroligin-1 knockout
      mice.
AB  - Neuroligin 1 (NLGN1) is a postsynaptic adhesion molecule that determines N-methyl
      d-aspartate receptor (NMDAR) function and cellular localization. Our recent work
      showed that Nlgn1 knockout (KO) mice cannot sustain neuronal activity occurring
      during wakefulness for a prolonged period of time. Since NMDAR-dependent neuronal
      activity drives an important vascular response, we used multispectral optical
      imaging to determine if the hemodynamic response to neuronal stimulation is
      modified in Nlgn1 KO mice. We observed that Nlgn1 KO mice show a 10% lower
      response rate to forepaw electrical stimulation compared to wild-type (WT) and
      heterozygote (HET) littermates on both the contra- and ipsilateral sides of the
      somatosensory cortex. Moreover, Nlgn1 mutant mice showed an earlier oxyhemoglobin
      peak response that tended to return to baseline faster than in WT mice. Analysis
      of the time course of the hemodynamic response also showed that HET mice express
      a faster dynamics of cerebrovascular response in comparison to WT. Taken
      together, these data are indicative of an altered immediate response of the brain
      to peripheral stimulation in Nlgn1 KO mice, and suggest a role for NLGN1 in the
      regulation of cerebrovascular responses. 

PMID- 25595980
TI  - Relationship between serotonin transporter occupancies and analgesic effects of
      AS1069562, the (+)-isomer of indeloxazine, and duloxetine in reserpine-induced
      myalgia rats.
AB  - Serotonin (5-HT) and norepinephrine (NE) have been implicated in the mediation of
      endogenous analgesic mechanisms via the descending inhibitory pain pathway in the
      brain, and dysfunction in both the 5-HT and NE systems has been suggested as an
      etiology of fibromyalgia (FM). Given that 5-HT reuptake inhibition in the brain
      appears to be associated with pain reduction, this mechanism might exert an
      analgesic effect also on pain associated with FM. In this case, it would be of
      interest to investigate the correlation of 5-HT transporter (SERT) occupancy with
      in vivo analgesic effect on pain associated with FM. Here, we investigated the
      relationship between SERT occupancies and the analgesic effects of AS1069562, the
      (+)-isomer of indeloxazine, and duloxetine, which are both 5-HT and NE reuptake
      inhibitors (SNRIs), on muscular pain in reserpine-induced myalgia (RIM) rats, an
      animal model of FM-like chronic pain. We also investigated the SERT occupancy
      level necessary for AS1069562 and duloxetine to exert analgesic effects on
      muscular pain. AS1069562 and duloxetine attenuated muscular hyperalgesia in RIM
      rats, representing the first findings to be reported regarding the analgesic
      effect of AS1069562 on pain associated with FM. SERT occupancy levels of
      AS1069562 and duloxetine increased in both dose- and plasma and brain
      concentration-dependent manners. SERT occupancy levels of AS1069562 and
      duloxetine were significantly correlated with efficacy on muscular pain
      thresholds in RIM rats. This finding concerning the precise correlation of SERT
      occupancy with in vivo analgesic effect on pain associated with FM is reported
      here for the first time. SERT occupancy level above 70% was necessary for
      AS1069562 and duloxetine to exert significant analgesic effects on muscular pain.
      These results suggest that SERT occupancy level is useful in determining
      appropriate analgesic doses of AS1069562 and duloxetine for treating pain
      symptoms in FM patients. 

PMID- 25595981
TI  - Cannabidiol increases survival and promotes rescue of cognitive function in a
      murine model of cerebral malaria.
AB  - Cerebral malaria (CM) is a severe complication resulting from Plasmodium
      falciparum infection that might cause permanent neurological deficits.
      Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with
      neuroprotective properties. In the present work, we evaluated the effects of CBD
      in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA
      (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day
      post-infection (dpi), at the peak of the disease), animals were treated with
      single or repeated doses of Artesunate, an antimalarial drug. All groups were
      tested for memory impairment (Novel Object Recognition or Morris Water Maze) and
      anxiety-like behaviors (Open field or elevated plus maze test) in different
      stages of the disease (at the peak or after the complete clearance of the
      disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor
      (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and
      hippocampus of experimental groups. PbA-infected mice displayed memory deficits
      and exhibited increase in anxiety-like behaviors on the 5dpi or after the
      clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF
      alpha and IL-6 increased in the hippocampus, while only IL-6 increased in the
      prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in
      the hippocampus and decreased levels of proinflammatory cytokines in the
      hippocampus (TNF-alpha) and prefrontal cortex (IL-6). Our results indicate that
      CBD exhibits neuroprotective effects in CM model and might be useful as an
      adjunctive therapy to prevent neurological symptoms following this disease. 

PMID- 25595982
TI  - Memory in time: electrophysiological comparison between reality filtering and
      temporal order judgment.
AB  - Orbitofrontal reality filtering (ORF) denotes a little known but vital memory
      control mechanism, expressed at 200-300ms after stimulus presentation, that
      allows one to sense whether evoked memories (thoughts) refer to present reality
      and can be acted upon, or not. Its failure induces reality confusion evident in
      confabulations that patients act upon and disorientation. In what way ORF differs
      from temporal order judgment (TOJ), that is, the conscious knowledge about when
      something happened in the past, has never been explored. Here we used evoked
      potential analysis to compare ORF and TOJ within a combined experimental task and
      within a comparable time frame, close to the experienced present. Seventeen
      healthy human subjects performed an experiment using continuous recognition tasks
      that combined the challenges of ORF and TOJ. We found that the two mechanisms
      dissociated behaviorally: subjects were markedly slower and less accurate in TOJ
      than ORF. Both mechanisms evoked similar potentials at 240-280ms, when ORF
      normally occurs. However, they rapidly dissociated in terms of amplitude
      differences and electrical source from 310 to 360ms and again from 530 to 560ms.
      We conclude that the task of consciously ordering memories in the immediate past
      (TOJ) is effortful and slow in contrast to sensing memories' relation with the
      present (ORF). Both functions invoke similar early electrocortical processes
      which then rapidly dissociate and engage different brain areas. The results are
      consistent with the different consequences of the two mechanisms' dysfunction:
      while failure of ORF has a known clinical manifestation (reality confusion as
      evident in confabulation and disorientation), the failure of TOJ, as tested here,
      has no such known clinical correlate. 

PMID- 25595983
TI  - Using the precision of the primate to study the origins of movement variability.
AB  - The study of motor control has long concerned itself with the origins of movement
      variability. Indeed, a common goal of many computational models of motor control
      is to predict the empirically observed patterns of movement variability.
      Competing models thus attempt to capture how the brain constrains variability
      that is detrimental and/or generates variability that might be beneficial. As
      humans, it is our own motor performance that interests us most we accept our
      variability as an essential part of being human, yet we are often frustrated when
      we cannot precisely repeat a desired movement. While movement variability is
      often productively studied in humans, uncovering its neural origins requires
      animal models. Below we describe recent research in which we were able to
      determine an important source of movement variability using a non-human primate
      model: the rhesus macaque. The macaque, much like the human, can produce flexible
      yet highly precise behavior. For this reason, among others, the macaque was an
      ideal model for the study of movement variability. 

PMID- 25595984
TI  - Real-time fMRI training-induced changes in regional connectivity mediating verbal
      working memory behavioral performance.
AB  - Working memory refers to the ability to temporarily store and manipulate
      information that is necessary for complex cognition activities. Previous studies
      have demonstrated that working memory capacity can be improved by behavioral
      training, and brain activities in the frontal and parietal cortices and the
      connections between these regions are also altered by training. Our recent
      neurofeedback training has proven that the regulation of the left dorsal lateral
      prefrontal cortex (DLPFC) activity using real-time functional magnetic resonance
      imaging (rtfMRI) can improve working memory performance. However, how working
      memory training promotes interaction between brain regions and whether this
      promotion correlates with performance improvement remain unclear. In this study,
      we employed structural equation modeling (SEM) to calculate the interactions
      between the regions within the working memory network during neurofeedback
      training. The results revealed that the direct effect of the frontoparietal
      connection in the left hemisphere was enhanced by the rtfMRI training.
      Specifically, the increase in the path from the left DLPFC to the left inferior
      parietal lobule (IPL) was positively correlated with improved performance in
      verbal working memory. These findings demonstrate the important role of the
      frontoparietal connection in working memory training and suggest that increases
      in frontoparietal connectivity might be a key factor associated with behavioral
      improvement. 

PMID- 25595985
TI  - Sex differences in the rapid and the sustained antidepressant-like effects of
      ketamine in stress-naive and "depressed" mice exposed to chronic mild stress.
AB  - During the past decade, one of the most striking discoveries in the treatment of
      major depression was the clinical finding that a single infusion of a sub
      anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces
      a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks)
      antidepressant effect in both treatment-resistant depressed patients and in
      animal models of depression. Notably, converging clinical and preclinical
      evidence support that responsiveness to antidepressant drugs is sex
      differentiated. Strikingly, research regarding the antidepressant-like effects of
      ketamine has focused almost exclusively on the male sex. Herein we report that
      female C57BL/6J stress-naive mice are more sensitive to the rapid and the
      sustained antidepressant-like effects of ketamine in the forced swim test (FST).
      In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at
      30 min and 5mg/kg at 24h post-injection), doses that were not effective in their
      male counterparts. Moreover, tissue levels of the excitatory amino acids
      glutamate and aspartate, as well as serotonergic activity, were affected in a sex
      dependent manner in the prefrontal cortex and the hippocampus, at the same time
      points. Most importantly, a single injection of ketamine (10mg/kg) induced sex
      dependent behavioral effects in mice subjected to the chronic mild stress (CMS)
      model of depression. Intriguingly, female mice were more reactive to the earlier
      effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h
      post-treatment, respectively) but the antidepressant potential of the drug proved
      to be longer lasting in males, as assessed in the splash test and the FST (days 5
      and 7 post-treatment, respectively). Taken together, present data revealed that
      ketamine treatment induces sex-dependent rapid and sustained neurochemical and
      behavioral antidepressant-like effects in stress-naive and CMS-exposed C57BL/6J
      mice.

PMID- 25595986
TI  - NGF but not BDNF overexpression protects hippocampal LTP from beta-amyloid
      induced impairment.
AB  - Two major neurotrophic factors, nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) are involved in a number of physiological processes
      associated with neuronal growth, survival and plasticity. There are an increasing
      number of papers demonstrating their ability to serve as neuroprotective
      molecules under various pathological conditions. At the same time, it remains
      unclear whether both NGF and BDNF have similar roles under pathological
      conditions and their effects on the electrophysiological properties of neurons
      after acute pathogen exposure. In the present paper we investigated the
      neuroprotective role of these two neurotrophins in a well-characterized model of
      beta-amyloid peptide (Abeta)-dependent impairment of long-term potentiation
      (LTP). Using lentiviral gene delivery we performed long-term elevation of
      neurotrophin expression in the dentate gyrus (DG) of rats. One week after virus
      injection acute brain slices were incubated with beta-amyloid (25-35) for 1h and
      afterward in vitro LTP induction was performed in medial perforant path-DG
      synapses. We demonstrate that chronic elevation of NGF but not BDNF concentration
      protects LTP induction from beta-amyloid action. Further inhibitory analysis
      suggests that the effect of NGF is mediated by PI3K-signaling cascade. 

PMID- 25595988
TI  - The size of non-hippocampal brain regions varies by season and sex in
      Richardson's ground squirrel.
AB  - Sex- and season-specific modulation of hippocampal size and function is observed
      across multiple species, including rodents. Other non-hippocampal-dependent
      behaviors exhibit season and sex differences, and whether the associated brain
      regions exhibit similar variation with sex and season remains to be fully
      characterized. As such, we examined the brains of wild-caught Richardson's ground
      squirrels (RGS; Urocitellus richardsonii) for seasonal (breeding, non-breeding)
      and sex differences in the volumes of specific brain areas, including: total
      brain volume, corpus callosum (CC), anterior commissure (AC), medial prefrontal
      cortex (mPFC), total neocortex (NC), entorhinal cortex (EC), and superior
      colliculus (SC). Analyses of variance and covariance revealed significant
      interactions between season and sex for almost all areas studied, primarily
      resulting from females captured during the breeding season exhibiting larger
      volumes than females captured during the non-breeding season. This was observed
      for volumes of the AC, mPFC, NC, EC, and SC. Where simple main effects of season
      were observed for males (the NC and the SC), the volume advantage favoured males
      captured during the NBr season. Only two simple main effects of sex were
      observed: males captured in the non-breeding season had significantly larger
      total brain volume than females captured in the non-breeding season, and females
      captured during the breeding season had larger volumes of the mPFC and EC than
      males captured in the breeding season. These results indicate that females have
      more pronounced seasonal differences in brain and brain region sizes. The extent
      to which seasonal differences in brain region volumes vary with behaviour is
      unclear, but our data do suggest that seasonal plasticity is not limited to the
      hippocampus and that RGS is a useful mammalian species for understanding seasonal
      plasticity in an ecologically relevant context. 

PMID- 25595989
TI  - Multigenerational prenatal stress increases the coherence of brain signaling
      among cortico-striatal-limbic circuits in adult rats.
AB  - Prenatal stress (PNS) is a significant risk factor for the development of
      psychopathology in adulthood such as anxiety, depression, schizophrenia and
      addiction. Animal models of PNS resemble many of the effects of PNS on humans and
      provide a means to study the accumulated effects of PNS over several generations
      on brain function. Here, we examined how mild PNS delivered during the third week
      in utero over four consecutive generations affects behavioral flexibility and
      functional signaling among cortical and limbic structures. These multi
      generational prenatally stressed (MGPNS) rats were not impaired on an odor-cued
      reversal learning task as compared to control animals. Unilateral field potential
      (FP) recordings from the medial prefrontal cortex, basolateral amygdala, ventral
      hippocampus, and striatal territories revealed widespread differences in brain
      signaling between these groups during the odor sampling phase of the task. The FP
      power was significantly lower in most structures across most frequency bands in
      MGPNS animals, and the relative increase in power from baseline during the task
      was lower for the beta band (12-30Hz) in MGPNS animals as compared to controls.
      The coherence of FPs between brain regions, however, was much higher in MGPNS
      animals among all structures and for most frequency bands. We propose that this
      pattern of changes in brain signaling reflects a simplification of network
      processing, which is consistent with reports of reduced spine density and
      dendritic complexity in the brains of animals receiving PNS. Our data support the
      proposal that recurrent ancestral stress leads to adaptations in the brain, and
      that these may confer adaptive behavior in some circumstances as compared to
      single-generation PNS. 

PMID- 25595987
TI  - Neuroanatomical and functional characterization of CRF neurons of the amygdala
      using a novel transgenic mouse model.
AB  - The corticotropin-releasing factor (CRF)-producing neurons of the amygdala have
      been implicated in behavioral and physiological responses associated with fear,
      anxiety, stress, food intake and reward. To overcome the difficulties in
      identifying CRF neurons within the amygdala, a novel transgenic mouse line, in
      which the humanized recombinant Renilla reniformis green fluorescent protein
      (hrGFP) is under the control of the CRF promoter (CRF-hrGFP mice), was developed.
      First, the CRF-hrGFP mouse model was validated and the localization of CRF
      neurons within the amygdala was systematically mapped. Amygdalar hrGFP-expressing
      neurons were located primarily in the interstitial nucleus of the posterior limb
      of the anterior commissure, but also present in the central amygdala. Secondly,
      the marker of neuronal activation c-Fos was used to explore the response of
      amygdalar CRF neurons in CRF-hrGFP mice under different experimental paradigms. C
      Fos induction was observed in CRF neurons of CRF-hrGFP mice exposed to an acute
      social defeat stress event, a fasting/refeeding paradigm or lipopolysaccharide
      (LPS) administration. In contrast, no c-Fos induction was detected in CRF neurons
      of CRF-hrGFP mice exposed to restraint stress, forced swimming test, 48-h
      fasting, acute high-fat diet (HFD) consumption, intermittent HFD consumption, ad
      libitum HFD consumption, HFD withdrawal, conditioned HFD aversion, ghrelin
      administration or melanocortin 4 receptor agonist administration. Thus, this
      study fully characterizes the distribution of amygdala CRF neurons in mice and
      suggests that they are involved in some, but not all, stress or food intake
      related behaviors recruiting the amygdala. 

PMID- 25595990
TI  - Necrostatin-1 mitigates mitochondrial dysfunction post-spinal cord injury.
AB  - Necrostatin-1 (Nec-1) is an inhibitor of necroptosis, playing an important role
      in inhibition of pathological death in the central nervous system (CNS). Our
      earlier study suggests that Nec-1 protects the injured spinal cord. In this
      study, we found that Nec-1 reduces the elevated Ca(2+) concentration in
      mitochondria post-injury and preserves the remarkably decreased mitochondrial
      membrane potential (MMP) level post-spinal cord injury (SCI). It also increases
      the generation of adenosine triphosphate (ATP) by promoting the activity of
      mitochondrial respiratory chain complex I instead of other complexes, which are
      significantly decreased due to the injury. Nec-1 also inhibits the release of
      cytochrome c in the mitochondria and protects the spinal cord from mitochondrial
      swelling post-SCI. Nec-1 promotes mitochondrial biogenesis by up-regulating
      mitochondrial transcription factor A (Tfam), in accordance with the mtDNA
      content. It also inhibits the up-regulation of mitochondrial fusion genes Mnf1,
      Mnf2 within 6h post-injury and adjusts the abnormal expression of mitochondrial
      fission gene Fis1. All these results indicate the improvement of mitochondrial
      functions in injured spinal cord after the treatment of Nec-1. This research
      revealed the mechanisms of functional protection of Nec-1 by mitigating
      mitochondrial dysfunction post-SCI. 

PMID- 25595991
TI  - Bisphenol A depresses monosynaptic and polysynaptic reflexes in neonatal rat
      spinal cord in vitro involving estrogen receptor-dependent NO-mediated
      mechanisms.
AB  - Bisphenol A (BPA), a toxic chemical from plastics, is known to produce locomotor
      abnormalities which may imply the alteration in synaptic activity at Ia-alpha
      motoneuron synapse also. However the effect of BPA on this synapse is not known.
      Therefore, this study was undertaken to examine the effect of BPA on reflexes
      originating at Ia-alpha motoneuron synapse in the spinal cord. The experiments
      were performed on isolated hemisected spinal cords from 4 to 6d rats. Stimulation
      of a dorsal root evoked segmental monosynaptic (MSR) and polysynaptic (PSR)
      reflex potentials in the corresponding ventral root. Nitrite content (indicator
      of NO activity) of cords was estimated in the presence of BPA with/without
      antagonists. Superfusion of BPA (3-100MUM) depressed the reflexes in a
      concentration- and time-dependent manner. The depression was ~20, ~50 and ~70% at
      10, 30 and 100MUM of BPA, respectively. The 50% depression occurred around 15min
      at 30MUM of BPA. Pretreatment with estrogen receptor (ERalpha) antagonist,
      tamoxifen, blocked the BPA-induced depression of reflexes, whereas, 17beta
      estradiol, ER agonist, did not depress the reflexes even up to 10MUM. Further,
      pretreatment with Nomega-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or
      hemoglobin (Hb) blocked the BPA-induced depression of spinal reflexes. Nitric
      oxide (NO) donor sodium-nitroprusside depressed the MSR and PSR in a
      concentration-dependent manner. The nitrite concentration of the cords exposed to
      BPA was 733MUM/gm of tissue (three times the saline group). Pretreatment with
      tamoxifen/l-NAME/Hb blocked the BPA-induced increase of nitrite levels. The
      present observations indicate that BPA depressed spinal synaptic transmission
      through ERalpha-dependent NO-mediated mechanisms. The altered synaptic activity
      may implicate for neurobehavioral locomotor abnormalities after exposure to BPA. 

PMID- 25595992
TI  - Lipoprotein lipase deficiency leads to alpha-synuclein aggregation and ubiquitin
      C-terminal hydrolase L1 reduction.
AB  - We have previously reported that presynaptic dysfunction and cognitive decline
      have been found in lipoprotein lipase (LPL) deficient mice, but the mechanism
      remains to be elucidated. Accumulating evidence supported that alpha-synuclein
      (alpha-syn) and ubiquitin C-terminal hydrolase L1 (UCHL1) are required for normal
      synaptic and cognitive function. In this study, we found that alpha-syn
      aggregated and the expression of UCHL1 decreased in the brain of LPL deficient
      mice. Reduction of UCHL1 was resulted from nuclear retention of DNA cytosine-5
      methyltransferase 1 in LPL knockout mice. Reverse changes were found in cultured
      cells overexpressing LPL. Furthermore, deficiency of LPL increased ubiquitination
      of alpha-syn. These results indicated that aggregation of alpha-syn and reduction
      of UCHL1 expression in LPL-deficient mice may affect synaptic function. 

PMID- 25595993
TI  - Mathematically gifted adolescents mobilize enhanced workspace configuration of
      theta cortical network during deductive reasoning.
AB  - Previous studies have established the importance of the fronto-parietal brain
      network in the information processing of reasoning. At the level of cortical
      source analysis, this eletroencepalogram (EEG) study investigates the functional
      reorganization of the theta-band (4-8Hz) neurocognitive network of mathematically
      gifted adolescents during deductive reasoning. Depending on the dense increase of
      long-range phase synchronizations in the reasoning process, math-gifted
      adolescents show more significant adaptive reorganization and enhanced
      "workspace" configuration in the theta network as compared with average-ability
      control subjects. The salient areas are mainly located in the anterior cortical
      vertices of the fronto-parietal network. Further correlation analyses have shown
      that the enhanced workspace configuration with respect to the global topological
      metrics of the theta network in math-gifted subjects is correlated with the
      intensive frontal midline theta (fm theta) response that is related to strong
      neural effort for cognitive events. These results suggest that by investing more
      cognitive resources math-gifted adolescents temporally mobilize an enhanced task
      related global neuronal workspace, which is manifested as a highly integrated
      fronto-parietal information processing network during the reasoning process. 

PMID- 25595995
TI  - Intratumoral CD68-, CD117-, CD56-, and CD1a-positive immune cells and the
      survival of Iranian patients with non-metastatic intestinal-type gastric
      carcinoma.
AB  - The purpose of this study was to investigate the prognostic significance of
      intratumoral immune cell counts in Iranian gastric cancer patients. A historical
      cohort study was conducted on fifty patients with non-metastatic intestinal-type
      gastric adenocarcinoma who underwent curative gastrectomy during 2004-2008 in
      Imam-Reza Hospital, Mashhad University of Medical Sciences. Immunohistochemistry
      (IHC) staining for CD56, CD68, CD117 and CD1a was performed to detect natural
      killer cells, macrophages, mast cells and Langerhans cells, respectively. The
      immune cells were counted, and the patients were then stratified into low or high
      immune cell counts. The prognostic significance of this grouping was analyzed
      using the Kaplan Meier method and Cox proportional hazards regression modeling.
      Thirty eight (76%) male and twelve (24%) female patients were enrolled in the
      study with a mean (+/-SD) age of 66.0 (+/-9.2) years. The median survival time
      was 15.0 (95%CI: 5.5-24.5) months. Natural killer cells, mast cells and
      Langerhans cells showed a positive effect on survival, whereas the reverse was
      true for macrophages. Multivariate analysis showed that the independent
      prognostic factors were location of the tumor (cardia/non-cardia), stage, the
      presence of extra-cytoplasmic mucin, tumor associated macrophage status
      (low/high), and tumor associated Langerhans cell status (low/high). In the
      studied population, gastric carcinoma proved to have a very poor prognosis.
      Multivariate analysis showed that the prognostic effect of natural killer and
      mast cells in tumoral tissue were dependent on the Langerhans cell count,
      defending the theory that dendritic cells mediate other immunocytes activities. 

PMID- 25595994
TI  - In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of
      activity-dependent neuroprotective protein in rat neurons.
AB  - Anesthetic doses of ketamine induce apoptosis, as well as gene expression of
      activity-dependent neuroprotective protein (ADNP), a putative homeodomain
      transcription factor in rat pups (P7). This study investigated if ketamine
      induced ADNP protein in a dose-dependent manner in vitro and in vivo using
      primary cultures of cortical neurons and neonatal pups (P7). In vivo
      immunohistochemistry demonstrated a sub-anesthetic dose of ketamine increased
      ADNP in the somatosensory cortex (SCC) which was previously identified to be
      damaged by repeated exposure to anesthetic doses of ketamine. Administration of
      low-dose ketamine prior to full sedation prevented caspase-3 activation in the
      hippocampus and SCC. Primary cultures of cortical neurons treated with ketamine
      (10 MUM-10mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent
      decrease in expanded growth cones. Furthermore, neuronal production and
      localization of ADNP varied as a function of both ketamine concentration and
      length of exposure. Taken together, these data support the model that ADNP
      induction may be partially responsible for the efficacy of a low-dose ketamine
      pre-treatment in preventing ketamine-induced neuronal cell death.

PMID- 25595996
TI  - The normal and pathologic renal medulla: a comprehensive overview.
AB  - The renal medulla comprises an intricate system of tubules, blood vessels and
      interstitium that is not well understood by most general pathologists. We
      conducted an extensive review of the literature on the renal medulla, in both
      normal and pathologic conditions. We set out in detail the points of key interest
      to pathologists: normal and pathological development, physiology, microscopic
      anatomy, histology and immunohistochemistry; and the specific and most common
      other types of disease associated with this part of the kidney: developmental
      abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive
      polycystic kidney diseases, medullary cystic kidney disease), inflammatory
      conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and
      dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors,
      chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma,
      other carcinomas, renal medullary fibroma and metastatic tumors). This condensed
      overview of the origin, function and pathology of the renal medulla, both in
      terms of development, inflammation and neoplastic processes, should help focus
      the interest of clinical pathologists on this widely overlooked part of the
      kidney. 

PMID- 25595998
TI  - Editorial introduction to the Neural Networks special issue on Deep Learning of
      Representations.

PMID- 25595997
TI  - Thyroid tumors of uncertain malignant potential: morphologic and
      imunohistochemical analysis of 29 cases.
AB  - INTRODUCTION: Thyroid tumors of uncertain malignant potential (TT-UMP) include
      follicular and well-differentiated tumors of UMP (FT-UMP/WDT-UMP), as it refers
      to the presence of questionable capsular/vascular invasion or incompletely
      developed papillary thyroid carcinoma (PTC)-type nuclear changes. However, these
      tumors are difficult to diagnose in most cases. We aimed to investigate whether
      immunohistochemistry (HBME-1, cytokeratin-19, galectin-3, CD56 and p63) provides
      additional information concerning such lesions. MATERIALS AND METHODS: We
      performed an immunohistochemical analysis on 29 TT-UMP cases (22 WDTs-UMP and 7
      FTs-UMP) selected from the Rhone Alpes thyroid cancer registry and Departement of
      Pathology, Tirgu-Mures Emergency County Hospital database. The
      clinicopathological and follow-up data were obtained. RESULTS: In the WDT-UMP
      group, HBME-1 was positive in 9/22 (40.9%) cases. CD56, a marker whose expression
      is reduced or absent in thyroid carcinoma, showed a "malignant" profile (no
      expression) in 13/22 (59.1%) cases. 7/22 (31.9%) cases were both HBME-1+ and CD56
      . One case showed the co-expression of HBME-1, CD56, galectin-3 and cytokeratin
      19. In the FT-UMP group, two cases were positive for HBME-1, other two for both
      galectin-3 and CK19 and only one case revealed a "malignant" CD56 profile. The
      follow-up data showed no distant metastases or persistent disease. CONCLUSION:
      Our study demonstrated very heterogeneous immunohistochemical profiles for TTs
      UMP, further supporting the borderline nature of these lesions. WDTs-UMP revealed
      a certain tendency toward a PTC profile, suggesting a possible pathogeneticlink
      between these two entities. However, immunohistochemistry is still to be regarded
      more as a supporting diagnostic tool, while morphological criteria should always
      prime in the diagnostic decision.

PMID- 25595999
TI  - Effectiveness of postoperative physical therapy for upper-limb impairments after
      breast cancer treatment: a systematic review.
AB  - OBJECTIVE: To systematically review the effectiveness of various postoperative
      physical therapy modalities and timing of physical therapy after treatment of
      breast cancer on pain and impaired range of motion (ROM) of the upper limb. DATA
      SOURCES: We searched the following databases: PubMed/MEDLINE, Cumulative Index to
      Nursing and Allied Health Literature, Embase, Physiotherapy Evidence Database,
      and Cochrane. Articles published until October 2012 were included. STUDY
      SELECTION: Only (pseudo) randomized controlled trials and nonrandomized
      experimental trials investigating the effectiveness of passive mobilization,
      manual stretching, myofascial therapy, and/or exercise therapy and timing of
      physical therapy after treatment for breast cancer are reviewed. Primary outcomes
      are pain of the upper limb and/or ROM of the shoulder. Secondary outcomes are
      decreased shoulder strength, arm lymphedema, limitations in activities of daily
      living, decreased quality of life, and wound drainage volume. Physical therapy
      modalities had to be started in the first 6 weeks after surgery. DATA EXTRACTION:
      Articles were selected by 2 independent researchers in 3 phases and compared for
      consensus. First the titles were analyzed, and then the selected abstracts and
      finally the full texts were reviewed. DATA SYNTHESIS: Eighteen randomized
      controlled trials were included in the review. Three studies investigated the
      effect of multifactorial therapy: 2 studies confirmed that the combination of
      general exercises and stretching is effective for the treatment of impaired ROM
      another study showed that passive mobilization combined with massage had no
      beneficial effects on pain and impaired ROM. Fifteen studies investigated the
      effectiveness of a single physical therapy modality. One study of poor quality
      found evidence supporting the beneficial effects of passive mobilization. The
      only study investigating the effect of stretching did not find any beneficial
      effects. No studies were found about the effectiveness of myofascial therapy in
      the postoperative phase. Five studies found that active exercises were more
      effective than no therapy or information on the treatment of impairments of the
      upper limb. Three studies supported the early start of exercises for recovery of
      shoulder ROM, whereas 4 studies supported the delay of exercises to avoid
      prolonged wound healing. CONCLUSIONS: Multifactorial physical therapy (ie,
      stretching, exercises) and active exercises were effective to treat postoperative
      pain and impaired ROM after treatment for breast cancer. High-quality studies are
      necessary to determine the effectiveness of passive mobilization, stretching, and
      myofascial therapy as part of the multifactorial treatment. In addition, the
      appropriate timing and content of the exercise programs need to be further
      investigated.

PMID- 25596001
TI  - Effect of exercise on depressive symptoms in adults with neurologic disorders: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: To review and quantify the effect of exercise on depression in adults
      with neurologic disorders. DATA SOURCES: CINAHL, Cochrane Register of Controlled
      Clinical Trials, EMBASE, ERIC, MEDLINE, PsycINFO, PubMed, and SPORTDiscus were
      searched, with the last search performed in May 2014. STUDY SELECTION: Included
      were randomized controlled trials conducted in adults with a diagnosed neurologic
      disorder that compared an exercise intervention group with a control group and
      used depression as an outcome measure. DATA EXTRACTION: Depression data were
      extracted independently by 2 authors. Methodological quality was assessed
      independently by 2 authors. DATA SYNTHESIS: Forty-three full-length articles were
      reviewed, and 26 trials met our inclusion criteria. These trials represented 1324
      participants with 7 different neurologic disorders: Alzheimer disease (n=4
      trials), migraine (n=1), multiple sclerosis (n=13), Parkinson disease (n=2),
      spinal cord injury (n=1), stroke (n=2), and traumatic brain injury (n=3). Data
      measuring depression were extracted and effect sizes were computed for 23 trials.
      Results from a meta-analysis yielded an overall effect size of .28 (SE=.07; 95%
      confidence interval, .15-.41; P=.00) favoring a reduction in depression outcomes
      after an exercise intervention compared with the control condition. Of note,
      interventions that met physical activity guidelines yielded an overall effect of
      .38 compared with .19 for studies that did not meet physical activity guidelines.
      CONCLUSIONS: This review provides evidence that exercise, particularly when
      meeting physical activity guidelines, can improve depressive symptoms in adults
      with neurologic disorders.

PMID- 25596002
TI  - Association between the severity of femoral condylar cartilage erosion related to
      knee osteoarthritis by ultrasonographic evaluation and the clinical symptoms and
      functions.
AB  - OBJECTIVE: To determine the association between the severity of femoral condylar
      cartilage erosion resulting from knee osteoarthritis (OA) by an ultrasonographic
      grading system and the clinical symptoms and functions. DESIGN: Cross-sectional
      study. SETTING: A tertiary center. PARTICIPANTS: Participants (N=101) with and
      without subjective complaints of knee discomfort were consecutively enrolled.
      Patients who had ever received knee arthroplasty, who had inflammatory arthritis,
      and whose knee flexion range of motion was <90 degrees  were excluded. A total of
      194 knees were evaluated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A
      semiquantitative ultrasonographic grading system was used to evaluate the
      severity of femoral condylar cartilage erosion. The clinical symptoms and
      functions were evaluated with the visual analog scale (VAS), Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. The
      association of the VAS/WOMAC/Lequesne index with the ultrasonographic grading was
      assessed. RESULTS: Positive linear associations were found between the
      ultrasonographic grading and the following: the VAS and the total scores and pain
      subscales of both the Lequesne index and WOMAC. Multivariate logistic regression
      analysis revealed grade-dependent association between VAS and ultrasonographic
      grading after adjusting for age, sex, and body mass index. The WOMAC and Lequesne
      index scores were associated with the ultrasonographic grading in more severe
      degrees, particularly in the pain subscales. CONCLUSIONS: This semiquantitative
      ultrasonographic grading system may well reflect the clinical symptoms and
      functions related to knee OA as evaluated by the VAS, WOMAC, and Lequesne index.
      This method provides a more comprehensive description and measurement of knee OA.

PMID- 25596003
TI  - Rice MULEs transpose in yeast.

PMID- 25596000
TI  - Performance-based outcomes of inpatient rehabilitation facilities treating hip
      fracture patients in the United States.
AB  - OBJECTIVE: To examine the influence of facility and aggregate patient
      characteristics of inpatient rehabilitation facilities (IRFs) on performance
      based rehabilitation outcomes in a national sample of IRFs treating Medicare
      beneficiaries with hip fracture. DESIGN: Secondary data analysis. SETTING: U.S.
      Medicare-certified IRFs (N=983). PARTICIPANTS: Data included patient records of
      Medicare beneficiaries (N=34,364) admitted in 2009 for rehabilitation after hip
      fracture. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Performance-based
      outcomes included mean motor function on discharge, mean motor change (mean motor
      score on discharge minus mean motor score on admission), and percentage
      discharged to the community. RESULTS: Higher mean motor function on discharge was
      explained by aggregate characteristics of patients with hip fracture (lower age
      [P=.009], lower percentage of blacks [P<.001] and Hispanics [P<.001], higher
      percentage of women [P=.030], higher motor function on admission [P<.001], longer
      length of stay [P<.001]) and facility characteristics (freestanding [P<.001],
      rural [P<.001], for profit [P=.048], smaller IRFs [P=.014]). The findings were
      similar for motor change, but motor change was also associated with lower mean
      cognitive function on admission (P=.008). Higher percentage discharged to the
      community was associated with aggregate patient characteristics (lower age
      [P<.001], lower percentage of Hispanics [P=.009], higher percentage of patients
      living with others [P<.001], higher motor function on admission [P<.001]). No
      facility characteristics were associated with the percentage discharged to the
      community. CONCLUSIONS: Performance-based measurement offers health policymakers,
      administrators, clinicians, and consumers a major opportunity for securing health
      system improvement by benchmarking or comparing their outcomes with those of
      other similar facilities. These results might serve as the basis for benchmarking
      and quality-based reimbursement to IRFs for 1 impairment group: hip fracture.

PMID- 25596004
TI  - Intervention of childhood and adolescents obesity in Shantou city.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of
      multicomponent school based intervention constituted of diet modification,
      regular exercise and psychosocial consultation on body status in overweight and
      obese children and adolescents. And to come up with an appropriate intervention
      protocol for controlling children and adolescents obesity in Shantou city.
      METHODS: Two schools were randomised to intervention group and control group
      respectively. A total of 41 students enrolled were diagnosed as overweight or
      obese. Twenty-six students of the intervention group completed the one-year
      intervention programme consisted of diet modification, regular exercise and
      psychological consultation except two of them were transferred to another school.
      The differences of BMI, anthropometric measures, metabolic profile and the scores
      of questionnaire and the scale were compared to evaluate the effects of the
      intervention programme. RESULTS: After one-year intervention, it observed in the
      intervention group that BMI-Z score, WHR and WHtR had significant improvements,
      and there was a nonsignificant trend (P=0.053) for a decrease in BMI-P. Fasting
      plasma glucose, cholesterol (CH) and low-density-lipoprotein cholesterol (LDL-C)
      levels in the intervention group showed nonsignificant trend for a decrease
      (PFPG=0.084, PCH=0.057, PLDLC=0.098), compared with a significant increase of
      triglycerides (TG) and LDL-C levels in the control group (PTG=0.041, PLDL
      C=0.038). There were some positive dietary, physical activity, or sedentary
      behaviour changes found in the students of the intervention group as the scores
      of the questionnaire got significant improvement (P=0.04). CONCLUSIONS: Our one
      year multicomponent school-based intervention programme did have positive effects
      to some extents on health state and lifestyle behaviour of overweight and obese
      children and adolescents, which indicated that it is feasible and important to
      implement such a school-based intervention programme in Shantou city.

PMID- 25596005
TI  - Exploring the role of gender norms in nutrition and sexual health promotion in a
      piloted school-based intervention: The Philadelphia UjimaTM experience.
AB  - Perceptions of masculinity and femininity influence behaviors and can be
      identified in young children and adolescents (Brannon, 2004). Thus, adolescents'
      engagement in health risk or promoting behaviors is influenced by perceptions of
      masculinity and femininity and the differences in expectations, norms and
      responsibilities for girls and boys (WHO, 2007). Girls and boys have different
      needs, and gender-based interventions that consider similarities as well as
      differences are needed. A gender-based nutrition and sexual health promotion
      program was developed and piloted by the Philadelphia Ujima Coalition in a high
      school setting. To explore the gender differences in adolescents' perceptions of
      the influence of gender norms on weight, nutrition, physical activity, and sexual
      health and the implication of these differences in future gender-integrated
      health promotion programming for youth, a content analysis of student and
      facilitator debriefing forms were implemented for the participating schools. The
      content analysis was used to identify central themes, concepts gained, and
      overall impact of the intervention sessions. Overall, gender norms influence
      healthy eating practices and activity through influencing perceptions of body
      type in adolescents. Gender norms also influence sexual activity and decision
      making through influencing perceptions of beauty, masculinity, femininity,
      pressures and popular concepts related to sexual activity. Thus, interventions
      that address gender may more effectively promote health and wellness in
      adolescents. 

PMID- 25596007
TI  - Combined airwayscope and fiberoptic bronchoscopic airway management in a patient
      with a tracheal bronchus.

PMID- 25596006
TI  - Follow-Up After Cardiac Surgery Should be Extended to at Least 120 Days When
      Benchmarking Cardiac Surgery Centers.
AB  - OBJECTIVE: Short-term (30 days) mortality frequently is used as an outcome
      measure after cardiac surgery, although it has been proposed that the follow-up
      period should be extended to 120 days to allow for more accurate benchmarking.
      The authors aimed to evaluate whether mortality rates 120 days after surgery were
      comparable to general mortality and to compare causes of death between the cohort
      and the general population. DESIGN: A multicenter descriptive cohort study using
      prospectively entered registry data. SETTING: University hospital. The cohort was
      obtained from the Western Denmark Heart Registry and matched to the Danish
      National Hospital Register as well as the Danish Register of Causes of Death. A
      weighted, age-matched general population consisting of all Danish patients who
      died within the study period was identified through the central authority on
      Danish statistics. PARTICIPANTS: A total of 11,988 patients (>15 years) who
      underwent cardiac-surgery at Aarhus, Aalborg and Odense University Hospitals from
      April 1, 2006 to December 31, 2012 were included. INTERVENTIONS: Coronary artery
      bypass grafting, valve surgery and combinations. MEASUREMENTS AND MAIN RESULTS:
      Mortality after cardiac surgery matches with mortality in the general population
      after 140 days. Mortality curves run almost parallel from this point onwards,
      regardless of The European system for cardiac operative risk evaluation
      (EuroSCORE) and intervention. The causes of death in the cohort differed
      statistically significantly from the background population (p<0.0001; one-sample
      t-test) throughout the first postoperative year. The leading cause of death in
      the cohort was cardiac (38%); 53% of which was categorized as heart failure. A
      total of 54% of these patients were assessed preoperatively as having normal or
      mildly impaired heart function (EuroSCORE). CONCLUSIONS: This study supported an
      extended follow-up period after cardiac surgery when benchmarking cardiac surgery
      centers. Regardless of preoperative heart function, heart failure was the
      consistent leading cause of death.

PMID- 25596008
TI  - The dark side of a pneumonia.

PMID- 25596009
TI  - Stability of glucagon-like peptide 1 and glucagon in human plasma.
AB  - To investigate the stability of glucagon-like peptide 1 (GLP-1) and glucagon in
      plasma under short- and long-term storage conditions. Pooled human plasma (n=20),
      to which a dipeptidyl peptidase 4 (DPP4) inhibitor and aprotinin were added, was
      spiked with synthetic GLP-1 (intact, 7-36NH2 as well as the primary metabolite,
      GLP-1 9-36NH2) or glucagon. Peptide recoveries were measured in samples kept for
      1 and 3 h at room temperature or on ice, treated with various enzyme inhibitors,
      after up to three thawing-refreezing cycles, and after storage at -20 and -80 
      degrees C for up to 1 year. Recoveries were unaffected by freezing cycles or if
      plasma was stored on ice for up to 3 h, but were impaired when samples stood at
      RT for more than 1 h. Recovery of intact GLP-1 increased by addition of a DPP4
      inhibitor (no ice), but was not further improved by neutral endopeptidase 24.11
      inhibitor or an inhibitor cocktail. GLP-1, but not glucagon, was stable for at
      least 1 year. Surprisingly, the recovery of glucagon was reduced by almost 50% by
      freezing compared with immediate analysis, regardless of storage time. Plasma
      handling procedures can significantly influence results of subsequent hormone
      analysis. Our data support addition of DPP4 inhibitor for GLP-1 measurement as
      well as cooling on ice of both GLP-1 and glucagon. Freeze-thaw cycles did not
      significantly affect stability of GLP-1 or glucagon. Long-term storage may affect
      glucagon levels regardless of storage temperature and results should be
      interpreted with caution. 

PMID- 25596010
TI  - The Refusal of Palliative Radiation in Metastatic Non-Small Cell Lung Cancer and
      Its Prognostic Implications.
AB  - CONTEXT: Patients with metastatic non-small cell lung cancer (NSCLC) have limited
      survival. Population studies have evaluated the impact of radiation refusal in
      the curative setting; however, no data exist concerning the prognostic impact of
      radiation refusal in the palliative care setting. OBJECTIVES: To investigate the
      patterns of radiation refusal in newly diagnosed patients with metastatic NSCLC.
      METHODS: Patients with Stage IV NSCLC diagnosed between 1988 and 2010 were
      identified in the Surveillance, Epidemiology, and End Results database.
      Univariate and multivariate analyses were used to identify predictors for refusal
      of radiation and the impact of radiation and refusal on survival in the
      palliative setting. RESULTS: A total of 285,641 patients were initially included
      in the analysis. Palliative radiation was recommended in 42% and refused by 3.1%
      of patients. Refusal rates remained consistent across included years of study. On
      multivariate analysis, older, nonblack/nonwhite, unmarried females were more
      likely to refuse radiation (P < 0.001 in all cases). Median survival for patients
      refusing radiation was three months vs. five months for those receiving radiation
      and two months for those whom radiation was not recommended. CONCLUSION: Patients
      with metastatic NSCLC who refuse recommended palliative radiation have a poor
      survival. Radiation refusal or the recommendation against treatment can serve as
      a trigger for integrating palliative care services sooner and contributes greatly
      to prognostic awareness. Further investigation into this survival difference and
      the factors behind refusal are warranted.

PMID- 25596011
TI  - Neuropathic Symptoms and Their Risk Factors in Medical Oncology Outpatients With
      Colorectal vs. Breast, Lung, or Prostate Cancer: Results From a Prospective
      Multicenter Study.
AB  - CONTEXT: Few studies have examined the prevalence and severity of treatment
      induced neuropathic symptoms in patients across different cancer types.
      OBJECTIVES: This study aimed to report the prevalence of numbness/tingling (N/T)
      and neuropathic pain in patients with colorectal cancer (CRC) vs. other cancers,
      describe the prevalence of moderate-to-severe N/T by specific clinical variables,
      and examine factors associated with the presence of these symptoms. METHODS: A
      total of 3106 outpatients with colorectal (n = 718), breast (n = 1544), lung (n =
      524), or prostate (n = 320) cancer were enrolled at any point in their treatment.
      Assessments were conducted at the initial visit and 28-35 days later. Patients
      reported pain and N/T; clinicians reported mechanism of pain and ranked the top
      three symptoms causing difficulties. RESULTS: Moderate-to-severe N/T was higher
      in patients with CRC relative to other cancer types (25.8% vs. 17.1%, P < 0.001);
      25% vs. 10.5% of clinicians rated N/T as a top three symptom for patients with
      CRC relative to other cancers (P < 0.001). The prevalence of neuropathic pain was
      comparable between patients with CRC and other cancers (P = 0.654). Patients with
      CRC, longer duration of cancer, prior therapy, on current therapy, older
      patients, and patients of black race experienced worse N/T. CONCLUSION: Patients
      with CRC experience significantly higher rates of N/T but comparable neuropathic
      pain, relative to patients with other cancers. Awareness of the prevalence and
      severity of neuropathic symptoms and their associated risk factors in this
      patient population is critical for both clinicians and patients.

PMID- 25596012
TI  - Characterization, antioxidant and immunomodulatory activities of polysaccharides
      from Prunella vulgaris Linn.
AB  - Water-soluble polysaccharides from Prunella vulgaris Linn (P. vulgaris) were
      fractionated using DEAE-Sepharose fast-flow column to obtain several eluents of
      water (PV-P1), 0.1M NaCl (PV-P2) and 0.2M NaCl (PV-P3). Structural analyses
      showed that PV-P1 had a higher molecular weight and degree of branching as
      compared to PV-P2 and PV-P3. Tertiary structure analyses indicated that PV-P1, PV
      P2 and PV-P3 did not have triple-helical conformation. PV-P2 and PV-P3 showed
      stronger antioxidant activities than PV-P1, as measured radical scavenging
      capacities. PV-P1 showed stronger immunomodulatory activities than PV-P2 and PV
      P3 in term of stimulation of the production of pro-inflammatory cytokines,
      including nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and
      interleukin-6 (IL-6) in murine macrophage RAW 264.7 cells. PV-P1, PV-P2 and PV-P3
      did not exhibit cytotoxicities against RAW 264.7 at the concentrations tested.
      These results suggest that P. vulgaris polysaccharides could be explored as
      potential antioxidant and immunomodulatory agents for the complementary medicine
      or functional foods. 

PMID- 25596013
TI  - Effects of high and low salt intake on left ventricular remodeling after
      myocardial infarction in normotensive rats.
AB  - The dietary-sodium restriction is a standard approach following an acute
      myocardial infarction (MI). We examined the hypothesis in which the use of a high
      or low-sodium diet would worsen post-infarction left ventricular remodeling in
      rats and facilitate the development of heart failure. Left coronary artery
      ligation or sham-operated (SO) was produced in male Wistar rats (250-290 g).
      After surgery, animals were assigned to one of the three diets: standard amount
      of sodium (0.3% NaCl, SO and MI groups), a high-sodium diet (0.6% NaCl, SO-High
      and MI-High groups), or a low-sodium diet (0.03% NaCl, SO-Low and MI-Low groups).
      Diets were provided for 8 weeks post-surgery. Mortality rate was elevated in high
      salt group (MI-Low, 21.4%; MI, 35.3%; MI-High, 47.6%). Contractility parameter
      was seen to be impaired in MI-Low animals (3195 +/- 211 mm Hg/s) compared with MI
      (3751 +/- 200 mm Hg/s). Low-salt diet did not prevent myocardial collagen
      deposition (MI-Low, 5.2 +/- 0.5%; MI, 5.0 +/- 0.4%) nor myocyte hypertrophy (MI
      Low, 608 +/- 41MU(2); MI, 712 +/- 53 MUm(2)) in left ventricle after MI. High
      salt intake increases collagen volume fraction (SO, 3.3 +/- 0.4%; SO-High, 4.7 +/
      0.4%) in animals sham, but no major changes after MI. Our results show that
      ventricular remodeling was not altered by immediate introduction of low sodium
      after MI, and it may be a safe strategy as a therapeutic intervention to avoid
      volume retention. However, high sodium can be harmful, accelerating the post
      infaction ventricular remodeling. 

PMID- 25596014
TI  - The UWEZO project-musculoskeletal health training in Kenya.
AB  - A major cause of disability and pain, musculoskeletal conditions (MSC) affect all
      aspects of people's lives and have a significant socioeconomic impact. Access to
      early diagnosis, effective treatments and rehabilitation enables people with MSCs
      to maintain their mobility, to work and to have a good quality of life. Despite
      the significant impact of MSC on health, social and economic well-being in
      Africa, services for MSC health remain extremely under-resourced. The UWEZO
      project is a collaboration between Kenyan, UK and Swedish rheumatologists,
      patients and researchers. It aims to improve access to basic musculoskeletal
      health care at the local level in communities across Kenya through the
      development of a sustainable training programme to raise the knowledge and skills
      of health professionals working in the community in the early detection,
      diagnosis and management of MSC. A team of physicians and patients have been
      trained to deliver an MSC education programme to health providers working in 11
      locations across Kenya. Over 500 health providers have been trained. The
      programme has the potential to be adapted for use in other low resource countries
      where access to care for musculoskeletal conditions is limited. 

PMID- 25596017
TI  - Epigenetics and cardiovascular disease.

PMID- 25596016
TI  - Radiosensitization to X-ray radiation by telomerase inhibitor MST-312 in human
      hepatoma HepG2 cells.
AB  - AIMS: Previous studies in malignant cells have shown that irradiation-induced
      upregulation of telomerase activity, not only protected damaged telomeres, but
      also contributed to DNA damage repair by chromosomal healing and increased
      resistance to irradiation. The purpose of the present study was to investigate
      the radiosensitizing effect of telomerase inhibitor MST-312 and the corresponding
      mechanism in the human hepatoma cell line HepG2. MAIN METHODS: Cell
      proliferation, telomerase activity, cell cycle distribution, DNA damage and
      repair, expression of p53, mitochondrial membrane potential, and cell apoptosis
      were measured with the MTT assay, real-time fluorescent quantitative PCR, flow
      cytometry, immunofluorescence, western blots, JC-1 staining, and Hoechst 33258
      staining, respectively. KEY FINDINGS: MST-312 effectively inhibited telomerase
      activity and showed relative weak toxicity to HepG2 cells at 4 MUM. Compared with
      irradiation alone, 4 MUM MST-312 pretreatment, followed by X-ray treatment,
      significantly reduced clonogenic potential. Aggravated DNA damage and increased
      sub-G1 cell fractions were observed. Further investigation found that homologous
      recombination (HR) repair protein Rad51 foci nuclear formation was blocked, and
      expression of p53 was elevated. These led to the collapse of mitochondrial
      membrane potential, and enhanced the apoptotic rate. SIGNIFICANCE: These data
      demonstrated that disturbances of telomerase function could enhance the
      radiosensitivity of HepG2 cells to X-ray irradiation by impairing HR repair
      processes. In addition, telomerase inhibitor MST-312 may be useful as an adjuvant
      treatment in combination with irradiation.

PMID- 25596015
TI  - Heart failure duration progressively modulates the arrhythmia substrate through
      structural and electrical remodeling.
AB  - AIMS: Ventricular arrhythmias are a common cause of death in patients with heart
      failure (HF). Structural and electrical abnormalities in the heart provide a
      substrate for such arrhythmias. Canine tachypacing-induced HF models of 4-6 weeks
      duration are often used to study pathophysiology and therapies for HF. We
      hypothesized that a chronic canine model of HF would result in greater electrical
      and structural remodeling than a short term model, leading to a more
      arrhythmogenic substrate. MAIN METHODS: HF was induced by ventricular tachypacing
      for one (short-term) or four (chronic) months to study remodeling. KEY FINDINGS:
      Left ventricular contractility was progressively reduced, while ventricular
      hypertrophy and interstitial fibrosis were evident at 4 month but not 1 month of
      HF. Left ventricular myocyte action potentials were prolonged after 4 (p<0.05)
      but not 1 month of HF. Repolarization instability and early afterdepolarizations
      were evident only after 4 months of HF (p<0.05), coinciding with a prolonged QTc
      interval (p<0.05). The transient outward potassium current was reduced in both HF
      groups (p<0.05). The outward component of the inward rectifier potassium current
      was reduced only in the 4 month HF group (p<0.05). The delayed rectifier
      potassium currents were reduced in 4 (p<0.05) but not 1 month of HF. Reactive
      oxygen species were increased at both 1 and 4 months of HF (p<0.05).
      SIGNIFICANCE: Reduced Ito, outward IK1, IKs, and IKr in HF contribute to EAD
      formation. Chronic, but not short term canine HF, results in the altered
      electrophysiology and repolarization instability characteristic of end-stage
      human HF.

PMID- 25596018
TI  - Aerobic exercise modulation of mental stress-induced responses in cultured
      endothelial progenitor cells from healthy and metabolic syndrome subjects.
AB  - AIM: Numerous studies have demonstrated that exercise acutely prevents the
      reduction in flow-mediated dilation induced by mental stress in subjects with
      metabolic syndrome (MetS). However, it is unknown whether a similar effect occurs
      in endothelial progenitors cells (EPCs). This study investigated whether exercise
      protects from the deleterious effect of mental stress on cultured EPCs in healthy
      subjects and those with MetS. MAIN METHODS: Ten healthy subjects (aged 31+/-2)
      and ten subjects with MetS (aged 36+/-2) were enrolled. Subjects underwent a
      mental stress test, followed immediately by either 40 min of leg cycling or rest
      across two randomized sessions: mental stress+non-exercise control (MS) and
      mental stress+exercise (MS+EXE). The Stroop Color-Word Test was used to elicit
      mental stress. Blood samples were drawn at baseline and following sessions to
      isolate mononuclear cells. These cells were cultured in fibronectin-coated plates
      for seven days, and EPCs were identified by immunofluorescence (acLDL(+)/ UEA-I
      Lectin(+)). KEY FINDINGS: All subjects presented similar increases in mean blood
      pressure and heart rate during the mental stress test (P<0.01) in both the MS and
      MS+EXE sessions. Number of EPCs was not different between groups at baseline in
      both sessions (P>0.05). The EPC response to MS and MS+EXE was increased in
      healthy subjects, whereas it was decreased in subjects with MetS (P<0.04). In
      healthy subjects, the EPC response to MS+EXE was greater than the response to MS
      alone (P=0.03). SIGNIFICANCE: An exercise session increased EPCs in healthy
      subjects but did not prevent the EPC reduction induced by mental stress among
      subjects with MetS.

PMID- 25596019
TI  - Idiopathic resorption of impacted mesiodentes: a radiographic study.
AB  - BACKGROUND: Although a large number of mesiodentes are left in situ, only a few
      are found in radiographs from epidemiological studies of adult populations. This
      leads to the development of a hypothesis that mesiodentes may be resorbed and
      disappear over time. The aim of this study was to radiographically investigate
      the frequency of resorptions and pathologies in relation to mesiodentes left in
      situ. METHODS: The study population consisted of 44 individuals, with 49
      mesiodentes left in situ at an early age. The individuals were 18-38 years old
      when re-examined. The inclusion criteria were that the mesiodentes had been
      diagnosed in childhood and left in situ, and that each individual was over 18
      years of age at the time of re-examination. Either digital or analogue intraoral
      radiographs were used at the re-examination and compared with earlier analogue
      radiographs. RESULTS: Forty-one per cent of the impacted mesiodentes showed
      resorptions-from limited to nearly complete resorption. No pathologies in
      connection to the mesiodentes were found. CONCLUSION: About half of the
      mesiodentes examined displayed resorption. No pathologies caused by the
      mesiodentes were recorded.

PMID- 25596020
TI  - Cognitive Dysfunction in Patients With Late-Life Somatic Symptom Disorder: A
      Comparison According to Disease Severity.
AB  - BACKGROUND: Late-life somatic symptom disorder (SSD) is characterized by various
      aging-associated factors, such as a functional decline, psychosocial problems,
      and cognitive dysfunction. However, the details of the cognitive dysfunction that
      occur in late-life SSD are still unknown. OBJECTIVE: The aims of this study were
      to reveal the cognitive profile of patients with late-life SSD and to evaluate
      how cognitive dysfunction affects disease severity. METHODS: We compared the
      cognitive profiles of patients with late-life SSD (n = 40) with those of normal
      control subjects (n = 21). In addition, we divided the patients with late-life
      SSD into mild-to-moderate (n = 24) and severe (n = 16) groups and compared the
      cognitive profiles of the 3 groups. RESULTS: Patients with late-life SSD
      exhibited a lower Mini-Mental State Examination total score and attention
      decline. In the 3-group comparison, the severe group had a lower Mini-Mental
      State Examination score and Frontal Assessment Battery score than the normal
      control group, whereas no significant difference was seen between the mild-to
      moderate and the normal control groups. CONCLUSIONS: Our data suggest that
      different cognitive patterns may exist depending on disease severity, possibly
      indicating differences in pathogenesis.

PMID- 25596021
TI  - Expectations and Level of Satisfaction of Patients and Their Physicians:
      Concordance and Discrepancies.
AB  - BACKGROUND: Identifying discrepancies between patients' expectations for support
      provided by their physicians, and physicians' appraisal of the support they
      provide to their patients, is a key factor in constructing effective doctor
      patient communication. OBJECTIVE: The current study proposes and explores a
      paradigm for assessing possible gaps and overlaps between perceptions of patients
      with cancer and physicians about the "actual" and the "ideal" (desired) emotional
      and cognitive support oncologists provide to patients. METHODS: Participants
      included 1027 patients with cancer and 47 senior oncologists. Patients' and
      physicians' levels of expectations and satisfaction with the emotional and
      cognitive support offered by physicians were assessed using a quantitative
      measure of discrepancy between the actual and the ideal situation. The measure
      was developed for this study and tested on a random sample of 200 patients and 17
      oncologists. RESULTS: The results indicated consistency between physicians' and
      patients' perceptions of the needs and support that the patients received.
      Nevertheless, oncologists did not feel highly trusted by their patients,
      oncologists desired less involvement of patients in the treatment plan than the
      patients expected. Oncologists thought that they actually provided the desired
      levels of explanation to patients' families, whereas patients thought their
      families got less explanations than expected. CONCLUSION: Actual and ideal levels
      of communication should be described from the points of view of both physicians
      and patients to better understand the complex picture of patient satisfaction.
      Oncologists should consider patients' expectations for support vs their own
      expectations to effectively address patients' needs.

PMID- 25596022
TI  - The importance of unresolved fatigue in depression: costs and comorbidities.
AB  - OBJECTIVE: To assess the cost outcomes of patients with a history of depression
      and clinically significant fatigue. METHODS: Adults with >= 2 claims with
      depression diagnosis codes identified from the HealthCore Integrated Research
      Database were invited to participate in this study linking survey data with
      retrospective claims data (12-mo presurvey and postsurvey periods). Patient
      surveys included measures for depression (Quick Inventory of Depressive
      Symptomatology), fatigue (Fatigue Associated with Depression Questionnaire),
      anxiety (7-item Generalized Anxiety Disorder scale), sleep difficulty (Athens
      Insomnia Scale), and pain (Brief Pain Inventory). After adjusting for demographic
      and clinical characteristics using propensity scores, postsurvey costs were
      compared between patients with and without fatigue using nonparametric
      bootstrapping methods. RESULTS: Of the 1982 patients who had completed the survey
      and had complete claims data, 653 patients had significant levels of fatigue.
      Patients with fatigue reported significantly higher scores, indicating greater
      severity, on measures of depression, pain, sleep difficulty, and anxiety (all p <
      0.05). These patients also had higher levels of overall medication use and were
      more likely to have lower measures of socioeconomic status than patients without
      significant levels of fatigue (all p < 0.05). Mean annual total costs were
      greater for patients with fatigue than those without fatigue ($14,462 vs $9971,
      respectively, p < 0.001). These cost differences remained statistically
      significant after adjusting for clinical and demographic differences.
      CONCLUSIONS: Clinically significant fatigue appears to add to the economic burden
      of depression. This reinforces the need for aggressive treatment of all symptoms
      and further examination of the variability of this relationship as patients
      approach remission.

PMID- 25596023
TI  - Barriers beyond clinical control affecting timely hospital discharge for a
      patient requiring guardianship.

PMID- 25596024
TI  - Get the lead out: potential progressive localized neural injury from retained
      cerebral bullet fragments without systemic toxicity.

PMID- 25596025
TI  - The stabilizing role of the Sabbath in pre-monarchic Israel: a mathematical
      model.
AB  - The three monotheistic cultures have many common institutions and some of them
      germinated in pre-monarchic Israel. Reasonably, the essential institutions were
      in place at that starting point; this work explores the possibility that the
      Sabbath is one of these institutions. Our mathematical examination points to the
      potential cultural, civic, and social role of the weekly Sabbath, that is, the
      Sabbath institution, in controlling deviation from social norms. It begins with
      an analogy between spread of transgression (defined as lack of conformity with
      social norms) and of biological infection. Borrowing well-known mathematical
      methods, we derive solution sets of social equilibrium and study their social
      stability. The work shows how a weekly Sabbath could in theory enhance social
      resilience in comparison with a similar assembly with a more natural and longer
      period, say between New Moon and Full Moon. The examination reveals that an
      efficient Sabbath institution has the potential to ensure a stable organization
      and suppress occasional appearances of transgression from cultural norms and
      boundaries. The work suggests the existence of a sharp threshold governed by the
      "Basic Sabbath Number ?0"-a critical observance of the Sabbath, or large enough
      ?0, is required to ensure suppression of transgression. Subsequently, the model
      is used to explore an interesting question: how old is the Sabbath? The work is
      interdisciplinary, combining anthropological concepts with mathematical analysis
      and with archaeological parallels in regards to the findings. 

PMID- 25596027
TI  - Mucinous anal adenocarcinoma invading the perianal region.

PMID- 25596026
TI  - Endoscopic submucosal dissection for the treatment of rectal carcinoid tumors 7
      16 mm in diameter.
AB  - OBJECTIVE: Small rectal carcinoid tumors (<10 mm) are often removed via
      endoscopic submucosal dissection (ESD). However, the use of ESD for tumors of an
      intermediate size (7-16 mm) is less well documented. This study aimed to evaluate
      the efficacy and safety of ESD compared with endoscopic mucosal resection using a
      cap (EMR-C) for the treatment of 7-16-mm rectal carcinoids. MATERIAL AND METHODS:
      From September 2007 to August 2012, 55 patients with large rectal carcinoid
      tumors were treated by EMR-C (30 cases) or ESD (25 cases). The en bloc resection
      rate, pathological complete response (pCR) rate, procedure time, and incidence
      rates of complications, local recurrence, and distant metastasis were evaluated.
      RESULTS: The basic and clinical characteristics of the patients in the two groups
      did not differ significantly (p > 0.05). The mean procedure time was longer for
      ESD than EMR-C (24.79 +/- 4.89 vs. 9.52 +/- 2.14 min, p < 0.001). The rates of en
      bloc resection and pCR were higher with ESD than with EMR-C (100 vs. 83.33 %, and
      100 vs. 70.00 %, respectively). No patients in the EMR-C group experienced
      complications. However, in the ESD group, two cases of perforation occurred, and
      one patient experienced delayed bleeding. These complications were successfully
      managed via endoscopical therapy. Five cases of local recurrence were detected
      after EMR-C, whereas no patients experienced recurrence after ESD. CONCLUSIONS:
      Compared with EMR-C, ESD appears to be a more favorable therapeutic option for
      the treatment of rectal carcinoid tumors less than 16 mm in diameter based on
      improved rates of pCR and local recurrence.

PMID- 25596028
TI  - Sugar catabolism in Aspergillus and other fungi related to the utilization of
      plant biomass.
AB  - Fungi are found in all natural and artificial biotopes and can use highly diverse
      carbon sources. They play a major role in the global carbon cycle by decomposing
      plant biomass and this biomass is the main carbon source for many fungi. Plant
      biomass is composed of cell wall polysaccharides (cellulose, hemicellulose,
      pectin) and lignin. To degrade cell wall polysaccharides to different
      monosaccharides, fungi produce a broad range of enzymes with a large variety in
      activities. Through a series of enzymatic reactions, sugar-specific and central
      metabolic pathways convert these monosaccharides into energy or metabolic
      precursors needed for the biosynthesis of biomolecules. This chapter describes
      the carbon catabolic pathways that are required to efficiently use plant biomass
      as a carbon source. It will give an overview of the known metabolic pathways in
      fungi, their interconnections, and the differences between fungal species. 

PMID- 25596030
TI  - Genetic control of asexual development in aspergillus fumigatus.
AB  - Aspergillus fumigatus is one of the most common fungi found in the environment.
      It is an opportunistic human pathogen causing invasive pulmonary aspergillosis
      with a high mortality rate in immunocompromised patients. Conidia, the asexual
      spores, serve as the main dispersal and infection agent allowing entrance of the
      fungus into the host through the respiratory tract. Therefore, understanding the
      asexual developmental process that gives rise to the conidia is of great interest
      to the scientific community and is currently the focus of an immense load of
      research being conducted. We have been studying the genetic basis that controls
      asexual development and gliotoxin biosynthesis in A. fumigatus. In this review,
      we discuss the genetic regulatory system that dictates conidiation in this
      important fungus by covering the roles of crucial genetic factors from the
      upstream heterotrimeric G-protein signaling components to the more specific
      downstream central activators of the conidiation pathway. In addition, other key
      asexual regulators including the velvet regulators, the Flb proteins and their
      associated regulatory factors are discussed. 

PMID- 25596029
TI  - The evolution of fungicide resistance.
AB  - Fungicides are widely used in developed agricultural systems to control disease
      and safeguard crop yield and quality. Over time, however, resistance to many of
      the most effective fungicides has emerged and spread in pathogen populations,
      compromising disease control. This review describes the development of resistance
      using case histories based on four important diseases of temperate cereal crops:
      eyespot (Oculimacula yallundae and Oculimacula acuformis), Septoria tritici
      blotch (Zymoseptoria tritici), powdery mildew (Blumeria graminis), and Fusarium
      ear blight (a complex of Fusarium and Microdochium spp). The sequential emergence
      of variant genotypes of these pathogens with reduced sensitivity to the most
      active single-site fungicides, methyl benzimidazole carbamates, demethylation
      inhibitors, quinone outside inhibitors, and succinate dehydrogenase inhibitors
      illustrates an ongoing evolutionary process in response to the introduction and
      use of different chemical classes. Analysis of the molecular mechanisms and
      genetic basis of resistance has provided more rapid and precise methods for
      detecting and monitoring the incidence of resistance in field populations, but
      when or where resistance will occur remains difficult to predict. The extent to
      which the predictability of resistance evolution can be improved by laboratory
      mutagenesis studies and fitness measurements, comparison between pathogens, and
      reconstruction of evolutionary pathways is discussed. Risk models based on fungal
      life cycles, fungicide properties, and exposure to the fungicide are now being
      refined to take account of additional traits associated with the rate of pathogen
      evolution. Experimental data on the selection of specific mutations or resistant
      genotypes in pathogen populations in response to fungicide treatments can be used
      in models evaluating the most effective strategies for reducing or preventing
      resistance. Resistance management based on robust scientific evidence is vital to
      prolong the effective life of fungicides and safeguard their future use in crop
      protection. 

PMID- 25596031
TI  - Escherichia coli ST131: The quintessential example of an international
      multiresistant high-risk clone.
AB  - Escherichia coli ST131 emerged during the early to mid-2000s is an important
      human pathogen, has spread extensively throughout the world, and is responsible
      for the rapid increase in antimicrobial resistance among E. coli. ST131 is known
      to cause extraintestinal infections, being fluoroquinolone resistant, and is
      associated with ESBL production most often due to CTX-M-15. Recent molecular
      epidemiologic studies using whole-genome sequencing and phylogenetic analysis
      have demonstrated that the H30 ST131 lineage emerged in early 2000s that was
      followed by the rapid expansion of its sublineages H30-R and H30-Rx. Escherichia
      coli ST131 clearly has all of the essential characteristics that define a high
      risk clone and might be the quintessential example of an international
      multiresistant high-risk clone. We urgently need rapid cost-effective detection
      methods for E. coli ST131, as well as well-designed epidemiological and molecular
      studies to understand the dynamics of transmission, risk factors, and reservoirs
      for ST131. This will provide insight into the emergence and spread of this
      multiresistant sequence type that will hopefully lead to information essential
      for preventing the spread of ST131.

PMID- 25596032
TI  - Colonization factors of enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a major cause of life-threatening
      diarrheal disease around the world. The major aspects of ETEC virulence are
      colonization of the small intestine and the secretion of enterotoxins which
      elicit diarrhea. Intestinal colonization is mediated, in part, by adhesins
      displayed on the bacterial cell surface. As colonization of the intestine is the
      critical first step in the establishment of an infection, it represents a
      potential point of intervention for the prevention of infections. Therefore,
      colonization factors (CFs) have been important subjects of research in the field
      of ETEC virulence. Research in this field has revealed that ETEC possesses a
      large array of serologically distinct CFs that differ in composition, structure,
      and function. Most ETEC CFs are pili (fimbriae) or related fibrous structures,
      while other adhesins are simple outer membrane proteins lacking any
      macromolecular structure. This chapter reviews the genetics, structure, function,
      and regulation of ETEC CFs and how such studies have contributed to our
      understanding of ETEC virulence and opened up potential opportunities for the
      development of preventive and therapeutic interventions.

PMID- 25596033
TI  - A sensitive assay for measuring aspartate-specific amino acid racemase activity.
AB  - D-Aspartate (D-Asp), a free D-amino acid found in mammals, plays crucial roles in
      the central nervous, neuroendocrine, and endocrine systems. In mammalian tissues,
      D-Asp oxidase (DDO) is a degradative enzyme that stereospecifically acts on D
      Asp. Asp racemase, a synthetic enzyme that produces D-Asp from L-Asp, has been
      identified in several lower organisms; however, the biosynthetic pathway of D-Asp
      in mammals remains to be fully clarified. The aim of this study was to establish
      a simple, accurate, and sensitive enzymatic method for the determination of Asp
      racemase activity. Using recombinant Streptococcus thermophilus Asp racemase as a
      model enzyme, two enzymatic methods for the determination of Asp racemase
      activity were optimized. In these methods, recombinant human DDO was used to
      degrade D-Asp formed from L-Asp by the Asp racemase reaction to 2-oxo acid, the
      amounts of which were then determined using a colorimetric assay. In one method,
      designated the coupling method, DDO was concomitantly included in the Asp
      racemase reaction mixture, and the Asp racemase reaction was readily coupled to
      the D-Asp degradative reaction by DDO during the incubation. In the other method,
      designated the separating method, an aliquot of the Asp racemase reaction mixture
      was mixed with DDO after the reaction to determine the amounts of D-Asp produced
      by Asp racemase. Under optimized conditions, the accuracy and sensitivity of
      these two methods were examined and compared, both to one another and
      conventional high-performance liquid chromatography (HPLC). The results presented
      here suggest that the coupling method is more accurate and sensitive than the
      other two methods and can be used for the determination of Asp racemase activity.
      The coupling method may help to advance our current understanding of the
      biosynthetic pathway of D-Asp in mammals.

PMID- 25596035
TI  - Administering intramuscular injections: how does research translate into practice
      over time in the mental health setting?
AB  - BACKGROUND: Increasingly, mental health nurses are expected to base their
      clinical practice on evidence based knowledge and many of the practice traditions
      that have passed between generations of nurses must now be examined within this
      scientific context. Since 2000, there has been an increasing debate on what is
      best practice for the administration of intramuscular injections particularly in
      relation to site selection, needle size and technique. Weight gain associated
      with second generation long acting antipsychotics influences the site and needle
      size for effective medication delivery. AIM: To determine intramuscular injecting
      practice choices made by nurses working in the mental health setting in 2006
      compared to those made by a similar group of nurses in 2012. METHODS: A
      descriptive cross sectional study conducted across two time points: 2006 (93
      participants) and 2012 (245 participants) utilising the same questionnaire
      designed to measure nurses' intramuscular injecting practice choices. RESULTS:
      Data were analysed using SPSS version 20 package. Six statistically significant
      practice changes were recorded related to needle size, site selection and the use
      of the Z-tracking technique. A continued higher usage of the dorsogluteal site
      was also reported in 2012 contrary to the recommendations in the current research
      for the ventrogluteal site. CONCLUSION: Whilst some practice changes occurred,
      translation of research into evidenced based practice is challenging and
      definitive best practice in the administration of intramuscular injections
      remains unclear. Education and randomised controlled trials are needed to provide
      the evidence to ensure the delivery of safe and effective intramuscular injecting
      practice.

PMID- 25596036
TI  - Dissecting the function of the different chitin synthases in vegetative growth
      and sexual development in Neurospora crassa.
AB  - Chitin, one of the most important carbohydrates of the fungal cell wall, is
      synthesized by chitin synthases (CHS). Seven sequences encoding CHSs have been
      identified in the genome of Neurospora crassa. Previously, CHS-1, -3 and -6 were
      found at the Spitzenkorper(Spk) core and developing septa. We investigated the
      functional importance of each CHS in growth and development of N. crassa. The
      cellular distribution of each CHS tagged with fluorescent proteins and the impact
      of corresponding gene deletions on vegetative growth and sexual development were
      compared. CHS-2, -4, -5 and -7 were also found at the core of the Spk and in
      forming septa in vegetative hyphae. As the septum ring developed, CHS-2-GFP
      remained at the growing edge of the septum until it localized around the septal
      pore. In addition, all CHSs were located in cross-walls of conidiophores. A
      partial co-localization of CHS-1-m and CHS-5-GFP or CHS-2-GFP occurred in the Spk
      and septa. Analyses of deletion mutants suggested that CHS-6 has a role primarily
      in hyphal extension and ascospore formation, CHS-5 in aerial hyphae, conidia and
      ascospore formation, CHS-3 in perithecia development and CHS-7 in all of the
      aforementioned. We show that chs-7/csmB fulfills a sexual function and chs-6/chsG
      fulfills a vegetative growth function in N. crassa but not in Aspergillus
      nidulans, whereas vice versa chs-2/chsA fulfills a sexual function in A. nidulans
      but not in N. crassa. This suggests that different classes of CHSs can fulfill
      distinct developmental functions in various fungi. Immunoprecipitation followed
      by mass spectrometry of CHS-1-GFP, CHS-4-GFP and CHS-5-GFP identified distinct
      putative interacting proteins for each CHS. Collectively, our results suggest
      that there are distinct populations of chitosomes, each carrying specific CHSs,
      with particular roles during different developmental stages.

PMID- 25596034
TI  - Results of induction chemotherapy in children older than 18 months with stage-4
      neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7).
AB  - PURPOSE: We report the response rate in children older than 18 months with stage
      4 Neuroblastoma, using a modified dose-intensive, response-adaptive, induction
      mN7 protocol. METHODS: From 2005 to 2012, 24 patients were treated with the mN7
      protocol. Phase 1 included five MSKCC N7 cycles and surgery and two high-dose
      cyclophosphamide-topotecan (HD-CT) cycles for those who did not achieve complete
      remission (CR) and negative bone marrow (BM) minimal residual disease (MRD)
      status (CR+MRD-). Phase 2 consisted of myeloablative doses of topotecan, thiotepa
      and carboplatin plus hyperfractionated RT. Phase 3 included isotretinoin and 3F8
      immunotherapy plus GM-CSF. BM MRD was monitored using GD2 synthase, PHOX2B and
      cyclin D1 mRNAs. RESULTS: After 3 cycles, all patients showed BM complete
      histological clearance and 6 (25 %) were MRD-. Twenty of 21 s-look surgeries
      achieved macroscopic complete resection. After 5 cycles and surgery, (123)I-MIBG
      scan was negative in 15 (62.5 %) cases, BM disease by histology was negative in
      23 (96 %) and 10 (42 %) patients were MRD-. Twelve (50 %) pts were in CR, 2 in
      very good partial response (VGPR), 9 partial response (PR) and one had
      progressive disease. With 2 HD-CT extra cycles, 17 (71 %) pts achieved CR+MRD-
      status moving to phase 2. Overall and event-free survival at 3 years for the 17
      patients who achieved CR+MRD- is 65 and 53 %, respectively, median follow-up 47
      months. Seven (29 %) patients never achieved CR+MRD-. Univariate Cox regression
      analysis shows CR+MRD- status after mN7 induction as the only statistically
      significant prognostic factor to predict overall survival. CONCLUSIONS: mN7
      induction regimen produced a CR+MRD- rate of 71 %. CR+MRD- status following
      induction was the only predictive marker of long-term survival.

PMID- 25596037
TI  - Determination of PCNA, cyclin D3, p27, p57 and apoptosis rate in normal and
      dexamethasone-induced intrauterine growth restricted rat placentas.
AB  - Intrauterine growth restriction (IUGR) is a major clinical problem, which causes
      perinatal morbidity and mortality. One of the reasons for IUGR is abnormal
      placentation. In rats, fetal-placental exposure to maternally administered
      glucocorticoids decreases birth weight and placental weight. Proper placental
      development depends on the proliferation and differentiation of trophoblasts. Our
      knowledge about the mitotic regulators that play key roles in synchronizing these
      events is limited. Also the mechanisms underlying the placental growth inhibitory
      effects of glucocorticoids have not been elucidated. The aim of this study was to
      investigate the immunolocalization, mRNA and protein levels of proliferating cell
      nuclear antigen (PCNA), cyclin D3, p27 and p57 in normal and dexamethasone
      induced IUGR Wistar rat placentas by reverse transcriptase polymerase chain
      reaction (RT-PCR), immunohistochemistry and Western blot. We also compared
      apoptotic cell numbers at the light microscopic level via terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling
      (TUNEL) and transmission electron microscopy. Glucocorticoid levels were higher
      in IUGR rats than in control rats after 60 and 120min of injection. We showed
      reduced gene and protein expressions of PCNA and cyclin D3 and increased
      expressions of p27 and p57 in IUGR placentas compared to control placentas.
      Apoptotic cell number was higher in the placentas of the IUGR group. In brief we
      found that maternal dexamethasone treatment led to a shift from cell
      proliferation to apoptosis in IUGR placentas. Dexamethasone induced placental and
      embryonal abnormalities which could be associated with reduced expressions of
      PCNA and cyclin D3, increased expressions of p27 and p57 and increased rate of
      apoptosis in IUGR placentas. 

PMID- 25596039
TI  - Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung
      injury in mice.
AB  - Acute lung injury (ALI) is a life-threatening disease characterized by serious
      lung inflammation and increased capillary permeability, which presents a high
      mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the
      natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus,
      has been reported to have definite anti-bacterial, anti-oxidant, and anti
      inflammatory activities. However, the effects of IF against lipopolysaccharide
      induced ALI have not been clarified. The aim of the present study is to explore
      the protective effects and potential mechanism of IF against LPS-induced ALI in
      mice. In this study, We found that pretreatment with IF significantly lowered LPS
      induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels
      of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also
      found that total cells, neutrophils and macrophages in BALF, MPO activity in lung
      tissues were markedly decreased. Besides, IF obviously inhibited lung
      histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These
      results suggest that IF has a protective effect against LPS-induced ALI, and the
      protective effect of IF seems to result from the inhibition of COX-2 protein
      expression in the lung, which regulates the production of PGE2. 

PMID- 25596040
TI  - Meals described as healthy or unhealthy match public health education in England.
AB  - Dietary guidelines for the general public aim to lower the incidence of nutrition
      related diseases by influencing habitual food choices. Yet little is known about
      how well the guidelines are matched by the actual practices that people regard as
      healthy or unhealthy. In the present study, British residents were asked in a
      cognitive interview to write a description of an occasion when either they ate in
      an unhealthy way or the eating was healthy. The reported foods and drinks, as
      well as sort of occasion, location, people present and time of day, were
      categorised by verbal and semantic similarities. The number of mentions of terms
      in each category was then contrasted between groups in exact probability tests.
      Perceived unhealthy and healthy eating occasions differed reliably in the sorts
      of foods and the contexts reported. There was also full agreement with the
      national guidelines on eating plenty of fruit and vegetables, eating small
      amounts of foods and drinks high in fat and/or sugar, drinking plenty of water,
      and cutting down on alcohol. There was a tendency to regard choices of bread,
      rice, potatoes, pasta and other starchy foods as healthy. Reported healthy and
      unhealthy eating did not differ in incidences of meat, fish, eggs, beans and
      other non-dairy sources of protein or of dairy foods and milk. These results
      indicate that operationally clear recommendations by health professionals are
      well understood in this culture but members of the public do not make clear
      distinctions in the case of foods that can be included in moderate amounts in a
      healthy diet. 

PMID- 25596038
TI  - Ilexgenin A induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor
      growth in vivo.
AB  - The present study aimed to investigate the anti-tumor activity of Ilexgenin A in
      B16-F10 murine melanoma and to evaluate its effect on the production of tumor
      associated inflammatory cytokines. In vitro, our study showed that Ilexgenin A
      inhibited the proliferation of B16-F10 murine melanoma cells in a dose- and time
      dependent manner, and this effect could be ascribed to the arrest of the cell
      cycle at G0/G1. In vivo, we evaluated the anti-tumor activity of Ilexgenin A in a
      tumor-bearing mouse model. The results showed that Ilexgenin A reduced the tumor
      weight by 51.13% (p<0.01). The Ilexgenin A treatment groups showed no apparent
      side effects during the treatment period. In addition, a histological analysis
      revealed that Ilexgenin A changed the cell morphology, and induced large areas of
      necrosis that correlated with a reduction in tumor size. The detection of
      inflammatory cytokines indicated that the IL-6 level decreased (p<0.001) and the
      TNF-alpha level increased (p<0.01) in mice treated with Ilexgenin A. Ilexgenin A
      also inhibited the IL-6 production of macrophages stimulated by melanoma
      conditioned medium (MCM) significantly (p<0.001). Importantly, Ilexgenin A
      dramatically prolonged survival time (p<0.001). In conclusion, Ilexgenin A could
      be regarded as a promising agent for the treatment of melanoma; it exerts anti
      melanoma activity by arresting the cell cycle at G0/G1 and regulating IL-6 and
      TNF-alpha production. 

PMID- 25596041
TI  - Chocolate equals stop. Chocolate-specific inhibition training reduces chocolate
      intake and go associations with chocolate.
AB  - Earlier research has demonstrated that food-specific inhibition training wherein
      food cues are repeatedly and consistently mapped onto stop signals decreases food
      intake and bodyweight. The mechanisms underlying these training effects, however,
      remain unclear. It has been suggested that consistently pairing stimuli with stop
      signals induces automatic stop associations with those stimuli, thereby
      facilitating automatic, bottom-up inhibition. This study examined this hypothesis
      with respect to food-inhibition training. Participants performed a training that
      consistently paired chocolate with no go cues (chocolate/no-go) or with go cues
      (chocolate/go). Following training, we measured automatic associations between
      chocolate and stop versus go, as well as food intake and desire to eat. As
      expected, food that was consistently mapped onto stopping was indeed more
      associated with stopping versus going afterwards. In replication of previous
      results, participants in the no-go condition also showed less desire to eat and
      reduced food intake relative to the go condition. Together these findings support
      the idea that food-specific inhibition training prompts the development of
      automatic inhibition associations, which subsequently facilitate inhibitory
      control over unwanted food-related urges. 

PMID- 25596042
TI  - The association between types of eating behaviour and dispositional mindfulness
      in adults with diabetes. Results from Diabetes MILES. The Netherlands.
AB  - Although healthy food choices are important in the management of diabetes, making
      dietary adaptations is often challenging. Previous research has shown that people
      with type 2 diabetes are less likely to benefit from dietary advice if they tend
      to eat in response to emotions or external cues. Since high levels of
      dispositional mindfulness have been associated with greater awareness of healthy
      dietary practices in students and in the general population, it is relevant to
      study the association between dispositional mindfulness and eating behaviour in
      people with type 1 or 2 diabetes. We analysed data from Diabetes MILES - The
      Netherlands, a national observational survey in which 634 adults with type 1 or 2
      diabetes completed the Dutch Eating Behaviour Questionnaire (to assess
      restrained, external and emotional eating behaviour) and the Five Facet
      Mindfulness Questionnaire-Short Form (to assess dispositional mindfulness), in
      addition to other psychosocial measures. After controlling for potential
      confounders, including demographics, clinical variables and emotional distress,
      hierarchical linear regression analyses showed that higher levels of
      dispositional mindfulness were associated with eating behaviours that were more
      restrained (beta = 0.10) and less external (beta = -0.11) and emotional (beta = 
      0.20). The mindfulness subscale 'acting with awareness' was the strongest
      predictor of both external and emotional eating behaviour, whereas for emotional
      eating, 'describing' and 'being non-judgemental' were also predictive. These
      findings suggest that there is an association between dispositional mindfulness
      and eating behaviour in adults with type 1 or 2 diabetes. Since mindfulness
      interventions increase levels of dispositional mindfulness, future studies could
      examine if these interventions are also effective in helping people with diabetes
      to reduce emotional or external eating behaviour, and to improve the quality of
      their diet. 

PMID- 25596043
TI  - [Current situation and challenges in companion diagnostics development].
AB  - The personalized health care, it is defined as a medical care which provide the
      optimal therapy for each individual in consideration of a patient's individual
      difference, such as a genetic background and a physiological state. A companion
      diagnosis to stratify a patient appropriately is essential for the spread of
      personalized health care, and it is important that a companion diagnostic reagent
      used for the companion diagnosis is properly developed and clinically applied.
      However, as for the development of companion diagnostics and pharmaceuticals that
      require it, there are still many challenges such as its business model of
      cooperation of diagnostics companies and pharmaceutical companies, also, the
      regulations related to companion diagnostics. Furthermore, even in clinical
      practice, there are many issues such as the way of reimbursement for companion
      diagnostics and also the handling of laboratory developed test (LDT) as companion
      diagnostics. These are issues that should continue to discuss with industry,
      government and academia. In this report, from the point of view of a diagnostics
      company, we discuss the various challenges in clinical applications from the
      development of companion diagnostics.

PMID- 25596044
TI  - [Recent progress in radiation therapy].
AB  - Causing selective damage to tumors is an important issue in radiation therapy.
      This is usually addressed using either a biological or a physical approach. The
      former includes chemoradiotherapy and a combination of targeted drugs and
      radiation whereas the latter includes stereotactic radiotherapy, intensity
      modulated radiotherapy and particle therapy. However, these sophisticated
      radiotherapy techniques are inadequate due to tumor movement and therefore 4
      dimensional radiotherapy which addresses this problem is being clinically
      investigated. 

PMID- 25596045
TI  - [Intensity modulated radiation therapy].
AB  - The development and successful clinical use of intensity modulated radiation
      therapy (IMRT) is a significant advance in radiation therapy. IMRT is
      particularly effective for cancers in complex anatomic regions such as the head
      and neck, and prostate, because the target volumes are contiguous to organs at
      risk. The success of IMRT strongly depends on the precise contouring of the
      target volumes and organs at risk. A significant benefit of IMRT with regard to
      xerostomia and quality of life has been reported for head and neck cancer. For
      prostate cancer, IMRT can deliver a high total dose of 76-80 Gy to the target
      volume without serious late toxicities.

PMID- 25596046
TI  - [Stereotactic body radiotherapy].
AB  - Stereotactic body radiotherapy(SBRT)is defined as the management and delivery of
      image-guided high-dose radiation therapy with tumor ablative intent within a
      short course of treatment. SBRT was more effective than 3D-CRT. In the phase II
      JCOG0403 trial for T1N0M0 non-small-cell lung cancer, the 3-year overall survival
      rate was 76% for operable patients and 59.9% for inoperable patients. Several
      authors reported the treatment results in various dose-fractionation schedules.
      However, the optimal dose, fractionation regimen, and the dose reference method
      are yet to be determined. Clinical trial s comparing SBRT and sublobar resection
      were planned but too few cases were enrolled to provide definitive evidence. SBRT
      for hepatocellular carcinoma(HCC) is a standard treatment option for patients who
      are ineligible for resection or radiofrequency ablation. A phase II trial for
      untreated non-metastatic primary HCC is ongoing in Japan which is expected to
      provide more supporting evidence.

PMID- 25596047
TI  - [Particle beam radiotherapy].
AB  - Recently, particle beam radiotherapy with protons or carbon ions has been used in
      cancer treatment. Energy deposition with particle beams increases as depth
      increases. Furthermore, carbon ion beams have stronger biological effects than X
      rays or proton beams, because carbon beams generate denser ionization along the
      pathway of the particles. In Japan, clinical study with carbon ions for cancer
      therapy was initiated in 1994 at the National Institute of Radiological
      Science(NIRS). Four treatment facilities are now in operation, including Gunma
      University Heavy Ion Medical Center. The experience with carbon ion radiotherapy
      at NIRS has demonstrated advantages for the following types of cancer. In terms
      of histological type, adenocarcinomas, sarcomas, and melanomas that are
      relatively radioresistant to conventional X-ray radiotherapy may be sensitive to
      carbon ion radiotherapy. Primary sites that may be sensitive include the head and
      neck region, lung, liver, prostate, bone and soft tissue, and pelvis(for
      recurrence of rectal cancer). Combined with surgery, cytotoxic drugs, molecular
      targeted drugs, and immunotherapy, carbon ion radiotherapy promises to be an
      important modality in the future. 

PMID- 25596048
TI  - [Brachytherapy].
AB  - Brachytherapy do require a minimal expansion of CTV to obtain PTV and it is
      called as ultimate high precision radiation therapy. In high-dose rate
      brachytherapy, applicators will be placed around or into the tumor and CT or MRI
      will be performed with the applicators in situ. With such image-guided
      brachytherapy (IGBT) 3-dimensional treatment planning becomes possible and DVH of
      the tumor and organs at risk can be obtained. It is now even possible to make
      forward planning satisfying dose constraints. Traditional subjective evaluation
      of brachytherapy can be improved to the objective one by IGBT. Brachytherapy of
      the prostate cancer, cervical cancer, and breast cancer with IGBT technique was
      described.

PMID- 25596049
TI  - [Cancer therapy using unsealed radioisotopes-the present and future].
AB  - Iodine-131 (I-131) has been used for the ablation of residual thyroid remnants
      and cancer cells in well-differentiated thyroid cancers. It has also been used
      for metastatic well-differentiated thyroid cancers, especially lung and bone
      metastases. For small lung metastases, I-131 treatment has curative potential,
      particularly in young patients. Suppression of the thyroid stimulating hormone is
      also important for prolonging the survival of thyroid cancer patients. Strontium
      89 (Sr-89) chloride has a mechanism similar to calcium, and it has been used for
      the treatment of bone metastases, especially osteoblastic metastases. It has been
      reported to have analgesic effects in an average of 76% of cases, and it is more
      effective if used in the early bone metastatic phase. Ibritumomab tiuxetan
      (Zevalin) is an anti-CD20 mouse monoclonal antibody labeled with Yttrium-90 (Y
      90). It is used for treatment-resistant low grade or follicular B-cell non
      Hodgkin's lymphomas and mantle lymphomas. Recently, radium-223 (Ra-223) has been
      used for bone metastases from castration resistant prostate cancers, and in a
      phase III trial, it has been proven to prolong survival of these patients. Cancer
      therapy using unsealed radioisotopes has been thought to be promising because it
      exhibits more targeted therapy than external beam irradiation. Therefore, if many
      more ideal targeting agents are developed in the future, this treatment might be
      used more commonly. As many agents such as I-131, Sr-89, and Ra-223 are available
      for treating bone metastasis, the combined use of other treatments such as high
      precision radiotherapy, bisphosphonates, hormonal agents, and molecular targeted
      agents should be investigated.

PMID- 25596050
TI  - [The timing of the appearance of oral mucositis induced by concurrent
      chemoradiotherapy with S-1 for head and neck cancer].
AB  - Oral mucositis is a frequent adverse event in patients receiving concurrent
      chemoradiotherapy for head and neck cancer. Although the management of oral
      mucositis is essential to improve treatment completion rates, no detailed studies
      on the time of oral mucositis appearance have been reported. We conducted a
      retrospective study on the timing of the appearance of oral mucositis induced by
      concurrent chemoradiotherapy with S-1 for head and neck cancer. A total of 11
      patients with head and neck cancer who received concurrent chemoradiotherapy with
      S-1 were examined. All patients developed oral mucositis within 13.8 +/- 5.6 days
      after the initiation of radiotherapy (20.4 +/- 8.1 Gy). In addition, the effects
      of pain-associated symptoms caused by oral mucositis on the patients' nutritional
      status, including reduction in caloric intake (24.4% +/- 31.1%), weight loss
      (5.2% +/- 5.2%), and duration of a regular diet (24.5 +/- 17.1 days), were
      observed and lasted until the completion of radiation therapy. The delineation of
      the timing of oral mucositis appearance has become a key motivator for the
      patients to perform oral care proactively to limit severity and serves as a
      necessary index for monitoring oral health and managing pain and nutrition.

PMID- 25596051
TI  - Effectiveness and safety of tegafur-gimeracil-oteracil potassium (TS-1) for
      metastatic breast cancer: a single-center retrospective study.
AB  - BACKGROUND: Tegafur-gimeracil-oteracil potassium (TS-1)is a drug that is used
      mainly as a third-line treatment or beyond for metastatic breast cancer(MBC).
      However, there is still insufficient evidence on its clinical effectiveness, and
      there are very few reports on clinical research using TS-1 up front. In this
      report, we examined the effectiveness and safety of TS-1 therapy for MBC.
      PATIENTS AND METHODS: The subjects were 46 patients with MBC who were treated
      with TS-1 between January 2005 and January 2013. These patients were
      retrospectively examined. RESULTS: The objective response rate to TS-1 therapy
      was 30.4%, clinical benefit rate (CBR)was 50.0%, and the median time to treatment
      failure was 10.7 months. When examined by site, the CBR was high locally (46.2%),
      in the lymph nodes (40.7%), in the bone (42.9%), and in the lungs and pleura
      (44.8%). However it was low in the liver(30.0%). The relationship was examined
      between clinicopathological factors and the effectiveness of TS-1 therapy. The
      objective response rate (ORR) was significantly higher for patients with disease
      free interval (DFI) of 2 years or more (p=0.039), TS-1 therapy used as third-line
      treatment or earlier (p=0.022), negative HER2 status (p=0.020), and no history of
      capecitabine (CAP)therapy (p=0.049). The CBR was significantly higher for
      patients with no visceral metastasis (p=0.032), TS-1 used as third-line treatment
      or earlier (p=0.019), negative HER2 status (p= 0.045), no history of CAP therapy
      (p=0.006), and no history of tegafur-uracil/doxifluridine therapy (p=0.031).
      Multivariate analysis showed that DFI of 2 years or more (p=0.035, odds
      ratio:0.104)was an independent predictor of effectiveness assessed by ORR. There
      were only 4 patients in whom the treatment was discontinued due to adverse event,
      and TS-1 was generally well tolerated. CONCLUSION: TS-1 was highly effective and
      well tolerated by patients with MBC. Its up-front use might enable the
      maintenance of satisfactory QOL and the enhancement of its clinical
      effectiveness.

PMID- 25596052
TI  - [Study of S-1 and oxaliplatin(SOX) plus bevacizumab as first-line therapy in
      patients with unresectable colorectal cancer].
AB  - We examined the safety and efficacy of S-1 and oxaliplatin plus bevacizumab
      (SOX+BV)as first-line therapy for advanced/recurrent unresectable colorectal
      cancer. The subjects were 14 patients with colorectal cancer who received >=3
      courses of SOX+BV therapy in our department.The dosing regimen for 1 course was
      as follows: BV (7.5 mg/kg) and oxaliplatin (130 mg/m(2)) were administered via
      intravenous drip infusion on the first day of the course, and S-1 was orally
      administered twice a day for 2 weeks, repeated every 3 weeks. All patients
      completed the study treatment, and the median number of courses completed was 9
      courses (range: 3-17 courses). In terms of anti-tumor efficacy, complete
      remission (CR) was observed in 1 patient (7.1%); partial remission (PR), in 9
      patients (64.3%); stable disease (SD), in 3 patients (21.4%); and progressive
      disease (PD), in 1 patient (7.1%), with a response rate of 71.4% and a disease
      control rate of 92.9%. The median relapse-free survival based on baseline PD was
      12 months, and the median relapse-free survival based on PD according to the
      Response Evaluation Criteria in Solid Tumors (RECIST) was 10 months.The most
      common adverse events observed included peripheral sensory neuropathy (100%),
      fatigue (68.3%), anorexia (57.1%), and leukopenia/neutropenia (35.7%); however,
      almost all adverse events were Grade<=2 and could be managed.The SOX+BV therapy
      demonstrated an antitumor efficacy similar to that observed with oxaliplatin,
      fluorouracil, and folinic acid (FOLFOX)+BV therapy without the use of a central
      venous port.Therefore, the SOX+BV therapy may be among the effective option as
      first-line therapy for advanced/recurrent colorectal cancer.

PMID- 25596053
TI  - [Assessment of risk factors for adverse events due to pemetrexed in patients with
      reduced renal function].
AB  - Pemetrexedis a key drug in the first and second -line therapy for non-small-cell
      lung cancer. It exhibits an increased area under the plasma drug concentration
      time curve, and it has a prolonged half -life when administered to patients with
      reduced renal function, resulting in a high frequency of neutropenia.
      Accordingly, pemetrexed is administered to these patients with caution. Herein,
      we retrospectively investigated the background characteristics of patients with a
      creatinine clearance rate (Ccr) of<45 mL/min, who experienced severe adverse
      events due to pemetrexed. Thirty-eight patients with a Ccr of <45 mL/min were
      administered pemetrexed. Of these patients, 13 (34%) developed severe adverse
      events (>=Grade 3) such as neutropenia, thrombocytopenia, and nausea. Multiple
      logistic regression analysis revealed that a Ccr of <30 mL/min (p= 0.033) and the
      concomitant use of non-steroidal anti-inflammatory drugs (p=0.012) were
      significant risk factors for adverse events. Therefore, whenever possible,
      pemetrexed administration should be avoided in patients with a Ccr of <30 mL/ min
      and in those receiving concomitant non-steroidal anti-inflammatory drugs.

PMID- 25596054
TI  - Efficacy of flutamide-combined androgen blockade therapy in advanced prostate
      cancer patients: a phase III randomized, comparative trial.
AB  - The efficacy of combined androgen blockade therapy consisting of flutamide, a
      nonsteroidal antiandrogen, plus an LH-RH agonist (F-CAB) was investigated in
      Japanese patients with untreated advanced prostate cancer (clinical stage D). The
      primary endpoint was overall survival (OS), while the secondary endpoints were
      disease-specific survival (DSS), progression- free survival (PFS), reduction of
      prostate specific antigen (PSA), anti-tumor effects, quality of life (QOL), and
      adverse drug reactions (ADRs). As of the median observation period of 1,293.5
      days, the F-CAB significantly prolonged DSS and PFS relative to LH-RH monotherapy
      (log rank test: p=0.0343 and 0.0017, respectively). The results of this study
      indicate the potential of F-CAB as a useful treatment for untreated advanced
      prostate cancer. Although additional study is considered necessary to determine
      the daily dosage of flutamide, the anti-tumor effects obtained from this study
      indicated that 375 mg/day is appropriate as a daily dosage, and 250 mg/day can
      also be considered when concern exists regarding the occurrence of complications
      or the development of ADRs, including liver function disorders. [Funded by Nippon
      Kayaku Co., Ltd., Japic CTI-050101].

PMID- 25596055
TI  - Initial safety and efficacy of cisplatin and gemcitabine combination chemotherapy
      for unresectable biliary tract cancer.
AB  - Cisplatin and gemcitabine combination chemotherapy has emerged as the standard
      treatment for advanced or recurrent biliary tract cancer and has been used in
      Japan since August 2011. We retrospectively reviewed and evaluated the toxicity
      and compliance of this combination chemotherapy from electronic medical records.
      From November 2011 to June 2012, 10 patients with unresectable biliary tract
      cancer underwent cisplatin and gemcitabine combination chemotherapy at our
      hospital. Grade 3/4 toxicities of neutropenia and thrombocytopenia were observed
      in 5 and 4 cases, respectively. Febrile neutropenia was observed in 3 cases.
      Grade 2 or worse anorexia was relatively common. Dose delays and reductions due
      to adverse events were needed in 8 patients. Cisplatin and gemcitabine
      combination chemotherapy for advanced biliary tract cancer can be safely
      performed with careful attention given to possible hematological toxicity and
      anorexia. 

PMID- 25596056
TI  - [A case of acute myeloid leukemia in an obese patient--determining the
      therapeutic dose of anticancer drugs].
AB  - Currently, there is no consensus to determine whether the therapeutic doses of
      anticancer drugs should be based on the actual or the ideal body weight of obese
      cancer patients. We performed induction and consolidation chemotherapy at doses
      calculated by using the actual body weight of an obese patient with acute myeloid
      leukemia (AML). A 47-year-old Japanese man presented with pancytopenia at our
      hospital, and he was diagnosed with AML (FAB classification M0). At the initial
      diagnosis, the patient was 170 cm tall and weighed 132 kg; therefore, his body
      surface area was 2.37 m(2). His performance status and organ functions were quite
      good. The calculations for determining doses of anticancer drugs required were
      based on his actual body weight. He received induction chemotherapy and achieved
      complete remission. Subsequently, he was treated with 4 courses of consolidation
      chemotherapy. Febrile neutropenia was a complication during each course, and it
      was relieved via myeloid recovery. Chemotherapy was administered every 4-5 weeks,
      except for the second course where platelet recovery was prolonged, and the
      prescribed treatment was completed. The guidelines of the American Society of
      Clinical Oncology (ASCO) recommend that physicians routinely use an obese
      patient's actual body weight to calculate the appropriate doses of almost all
      chemotherapy drugs. Therefore, the ease and compromised usage of under-dosing
      because of heaviness owing to obesity should be avoided.

PMID- 25596058
TI  - [A case of early gastric cancer with multiple synchronous bone metastases treated
      complete response with S-1+CDDP].
AB  - We report a case of complete response (CR) following induction chemotherapy using
      S-1 for a patient with early gastric cancer accompanied by multiple synchronous
      bone metastases. An asymptomatic 70-year-old woman was diagnosed with early
      gastric cancer by upper gastrointestinal endoscopy during a periodic medical
      examination. An abdomino-pelvic computed tomography (CT) scan revealed no primary
      tumor in the stomach and the absence of lymph node or liver metastases. However,
      osteoplastic changes were detected in the lumbar vertebrae and the ilium.
      Multiple synchronous bone metastases from early gastric cancer were detected on
      magnetic resonance imaging, bone scintigraphy, and positron emission tomography-
      CT. After a regimen consisting of 15 courses of S-1 plus cisplatin (CDDP), and an
      additional 5 courses of S-1 were administered, clinical CR was confirmed for the
      bone metastases. Laparoscopic distal gastrectomy with D1 lymphadenectomy was
      performed for treating the primary gastric cancer 33 months after the initiation
      of chemotherapy. Pathological CR was also achieved for the primary gastric
      cancer. Imaging analysis did not show disease progression 48 months after the
      initiation of chemotherapy. Synchronous bone metastases from early gastric cancer
      are extremely rare, and a good outcome was achieved in the present case through
      induction chemotherapy.

PMID- 25596057
TI  - [A case of thymic cancer effectively treated by weekly paclitaxel combined with
      carboplatin].
AB  - A 65-year-old woman with left chest pain, back pain, and palpitation that had
      persisted for 2 months was referred to our hospital. Computed tomography of her
      chest showed an anterior mediastinal tumor with mediastinal lymphadenopathy, left
      pleural effusion, and pericardial effusion. Endobronchial ultrasound-guided
      transbronchial needle aspiration of the subcarinal lymphadenopathy was performed.
      The pathological findings and other examinations such as bone scintigraphy
      suggested advanced thymic cancer (stage IV b according to the Masaoka
      classification of thymic epithelial tumors). The patient was treated with
      combination chemotherapy of carboplatin(area under the curve [AUC]=6, 656
      mg/body, day 1) and weekly paclitaxel (70 mg/m2, 100 mg/body, days 1, 8, and 15).
      After 4 cycles of chemotherapy, a partial response was achieved and the
      pericardial effusion disappeared. The patient did not experience any severe
      toxicity, except for grade 1 nausea, grade 2 anemia, and grade 2 alopecia. Weekly
      paclitaxel combined with carboplatin appears to be a useful regimen with minimal
      toxicity for advanced thymic cancer.

PMID- 25596059
TI  - [Systemic chemotherapy and surgery for recurrent metachronous liver metastases
      with peritoneal dissemination from triple colon cancers-a case report].
AB  - Although the first-line treatment for liver metastases arising from colorectal
      cancer is surgery, it is unknown whether this treatment is equally effective for
      liver metastases with peritoneal dissemination. We report a case of long-term
      survival after oxaliplatin-based chemotherapy and surgery for metachronous liver
      metastases with peritoneal dissemination from triple colon cancer. A 76-year-old
      man with a history of stage III descending colon cancer developed recurrent
      localized peritoneal dissemination and multiple liver metastases 30 months after
      surgery. He underwent partial liver resection, partial peritoneal resection, and
      8 courses of capecitabine plus oxalitlatin (XELOX). There has been no disease
      recurrence 75 months after the initial surgery. While though there is no
      consensus for treatment of liver metastasis with peritoneal dissemination,
      surgery combined with systemic chemotherapy may be beneficial.

PMID- 25596060
TI  - [A case in which metachronous ovarian metastasis developed 9 months after surgery
      for cecal carcinoma perforation and peritonitis].
AB  - The patient was a 78-year-old woman who underwent surgery for cecal carcinoma
      perforation and peritonitis (ileocecal resection and ileostomy)in January 2012.
      Liver metastasis was observed on the postoperative computed tomography (CT) scan
      and chemotherapy was performed. However, in October, a CT scan revealed a tumor,
      9 cm in diameter, in the right ovary. Based on the results of a positron emission
      tomography (PET)-CT scan, this was suspected to be primary or metastatic ovarian
      cancer, and bilateral salpingo-oophorectomy was performed the following January.
      Histopathology and immunostaining indicated that this was a cytokeratin (CK) 20
      positive and CK7-negative adenocarcinoma, and the patient was diagnosed with
      metastatic cecal carcinoma.

PMID- 25596061
TI  - [Complete response of locally recurrent anorectal cancer to proton beam therapy
      alone--a case report].
AB  - We report a case of locally recurrent anorectal cancer treated with proton beam
      therapy (PBT) alone that led to a clinically complete response. A 70-year-old
      woman with paraparesis due to infantile paralysis underwent abdominoperineal
      resection (APR) and D3 lymphadenectomy for anorectal cancer (PERb, type 2, 50*40
      mm, muc-tub1, M1a[lung], Stage IV a]. Three months after APR, right middle and
      right lower lobectomies were performed for synchronous lung metastases. Adjuvant
      chemotherapy was not administered. One year and 8 months after APR, computed
      tomography (CT) showed local recurrence of the tumor (29*28 mm), which contacted
      the right ischial spine. Pelvic exenteration combined with sacral resection was
      not performed because of the patient's poor performance status. PBT (70 Gy
      [RBE]/25 F/5 week) was administered for treatment of the recurred tumor. CT
      revealed that the tumor disappeared 1 year after PBT, which was defined as
      complete response. The patient is alive and has not experienced recurrence for 7
      years.

PMID- 25596062
TI  - Renal impairment, mild hyperkalemia and atrioventricular conduction blockade: a
      potentially hazardous combination.

PMID- 25596063
TI  - Multiple sclerosis in children and adolescents. An important differential
      diagnosis of acute neurological disease.
AB  - AIM: Multiple sclerosis (MS) has traditionally been considered a disease of
      adults. However, in recent years, there have been numerous reports about the
      disease occurring in childhood and adolescence. The purpose of this article is to
      document Norwegian experience of this population based on clinical observations
      and neuroradiological findings. METHODS: Children and adolescents diagnosed with
      MS at the Department of Child Neurology, Oslo University Hospital, between 1
      January 2004 and 1 May 2012 were included. Gender, previous diseases, age,
      symptoms at first attack, spinal fluid findings and cerebral magnetic resonance
      tomography (MRI) findings were recorded. The course of the disease, treatment and
      sequelae was noted. RESULTS: The study includes 18 patients who received MS
      diagnosis. Median age at onset was 10 years and six months. The presenting
      symptoms and MRI findings varied. Almost all patients were treated with steroids
      in the acute phase and later with interferon-beta. Some patients were treated
      with natalizumab when there was lack of efficiency of interferon-beta. Seven
      patients developed permanent, moderate sequelae in terms of motor, sensory, or
      cerebellar symptoms. Nine patients had cognitive difficulties and 11 specified
      increased fatigability. CONCLUSION: MS in children and adolescents is a disease
      with varying acute neurological symptoms and findings. The patients were treated
      with the same medicines as adults with MS and tolerated it well. We found that
      cognitive sequelae and fatigue were common also in this young age group.

PMID- 25596064
TI  - An 8-year old boy with continuous spikes and waves during slow sleep presenting
      with positive onconeuronal antibodies.
AB  - OBJECTIVE: To determine the etiology of epilepsy with continuous spikes and waves
      during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an
      8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. MATERIAL
      & METHODS: A combination of clinical characterization and follow-up, video EEG
      and laboratory investigations. RESULTS: We report the case of an 8-year old boy
      with a history of neuroblastoma and opsoclonus-myoclonus, who presented with
      intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES.
      Although the patient's neuroblastoma had been successfully treated 8 years prior
      to presentation and an extensive workup did not show a tumor reoccurrence,
      testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5
      antibodies. High-dose intravenous methylprednisolone and a taper of oral
      methylprednisolone were given, leading to a significant clinical improvement.
      During the taper the patient's condition and EEG manifestations deteriorated
      again necessitating another cycle of steroid therapy, which lead to a stable
      improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2
      and anti-CV2/CRMP5 antibodies remained undetectable. CONCLUSION: This case
      suggests that onconeuronal antibodies may be involved in the pathogenesis of
      CSWS/ESES.

PMID- 25596065
TI  - Cerebral palsy: phenotypes and risk factors in term singletons born small for
      gestational age.
AB  - BACKGROUND AND OBJECTIVES: Children born small for gestational age (SGA) are at
      increased risk of developing cerebral palsy (CP). The pathophysiology behind this
      association remains unclear. We compare the clinical profile of children with CP
      born SGA to other children with CP. We hypothesize that differences noted will
      support antenatal causes of CP in children born SGA. METHODS: We conducted a
      retrospective cohort study of term singletons with CP, extracting data from the
      Canadian Cerebral Palsy Registry. SGA was determined as birth weight for
      gestational age and sex below the tenth percentile. RESULTS: Mothers of children
      with CP born SGA were more likely to be of African-American ethnicity (RR 2.54,
      95% CI 1.20-5.39), have intrauterine infections (RR 2.22, 95% CI 1.09-4.50) and
      have gestational hypertension (RR 1.78, 95% CI 1.06-3.00). Children with CP born
      SGA had smaller head circumferences at birth (p < 0.001) and higher frequencies
      of emergency cesarean-section (RR 1.53, 95% CI 1.22-1.92), birth asphyxia (RR
      1.53, 95% CI 1.0-2.32), and placental abnormalities (RR 1.45, 95% CI 1.00-2.10).
      Children with CP born SGA had greater fine motor (RR 1.46, 95% CI 1.02-2.11),
      gross motor (RR 1.53, 95% CI 1.12-2.10) and communication impairment (RR 1.24,
      95% CI 1.10-1.40), and a higher frequency of cognitive impairment (RR 1.33, 95%
      CI 1.06-1.69). CONCLUSION: Children with CP born SGA have different clinical
      factors and phenotypic profiles than other children with CP. These differences
      support the hypothesis of antenatal and perinatal causes of CP in children born
      SGA. Future case control studies would be desired to further define this causal
      pathway.

PMID- 25596066
TI  - Paroxysmal tonic upward gaze as a presentation of de-novo mutations in CACNA1A.
AB  - OBJECTIVE: Paroxysmal tonic upward gaze was initially described as a benign
      phenomenon with negative investigations and eventual complete resolution of
      symptoms. Later publications demonstrated that a similar clinical picture may
      arise from structural brain lesions, channelopathies, neurotransmitter disorders,
      and epileptic seizures. CACNA1A related disorders manifest as a wide spectrum of
      paroxysmal neurological disorders: episodic ataxia 2, hemiplegic migraine, benign
      paroxysmal torticollis of infancy, and paroxysmal vertigo. Paroxysmal tonic
      upward gaze as a phenomenon in patients with mutations in the CACNA1A gene has
      only been reported once. METHODS: We describe three patients with multiple
      episodes of paroxysmal tonic upward gaze that appeared during the first months of
      life. In addition the patients demonstrated motor and language delay and
      cerebellar ataxia. A sequence analysis of the CACNA1A gene in one patient and
      whole exome sequencing in the other patients were performed. RESULTS: Sequence
      analysis of the CACNA1A gene in one patient and whole exome sequencing in the two
      other patients revealed 3 different de-novo mutations in the CACNA1A gene.
      CONCLUSION: CACNA1A mutations should be evaluated in infants and young children
      with paroxysmal tonic upgaze especially if associated with developmental delay,
      cerebellar signs, and other types of paroxysmal event.

PMID- 25596067
TI  - Widespread intracranial calcifications in the follow-up of a patient with
      cartilage-hair hypoplasia--anauxetic dysplasia spectrum disorder: a coincidental
      finding?
AB  - BACKGROUND/PURPOSE: Intracranial calcifications have been identified in many
      neurological disorders. To our knowledge, however, such findings have not been
      described in cartilage-hair hypoplasia - anauxetic dysplasia spectrum disorders
      (CHH-AD), a group of conditions characterized by a wide spectrum of clinical
      manifestations. METHODS/RESULTS: We report a 22-year old female patient,
      diagnosed with this disorder during her first year of life, and in whom bilateral
      intracranial calcifications (frontal lobes, basal ganglia, cerebellar dentate
      nuclei) were discovered by brain MRI at the age of 17 years. CONCLUSION: The
      etiology of this finding remains unclear. Some causes of such deposits can be of
      a reversible nature, thus prompting early recognition although their consequences
      on clinical outcome remain mostly unknown.

PMID- 25596068
TI  - Will Australians pay for health care advice from a community pharmacist? A video
      vignette study.
AB  - BACKGROUND: Large proportion of Australians have access to pharmacists' health
      advice at no cost. The impact of a proposed co-payment levy for general
      practitioner (GP) consultation by Australian government is unclear. This raises
      an interesting question about consumers' perceived value of health-related
      consultations. OBJECTIVE: This survey of representative sample of Western
      Australians explores the hypothesis that Australians are willing to pay for
      advanced model of pharmacy consultation. METHODS: Two videos illustrating current
      services and quality-enhanced-service (QES) incorporating systematic assessment
      of symptoms and referral to GP if necessary, were used. Participants viewed
      videos online and completed a willingness-to-pay (WTP) questionnaire about their
      perception and WTP for each service. Logistic regression and McNemar tests were
      used to identify WTP groups. RESULTS: Of the 175 respondents, one in nine
      (19/175, 11%) were willing to pay and (35/175) 20% might consider paying for
      advice at pharmacies as per current-practice. Almost one in four (49/175, 28%)
      were willing to pay and (47/175) 27% would consider paying for QES (McNemar Test
      P < 0.001). CONCLUSIONS: The majority of West Australians may be willing to pay
      for consultation at pharmacies that offers more private, time-intensive
      experience with documented GP referral where required. Further research is
      warranted to test WTP with actual customers to confirm these results.

PMID- 25596070
TI  - A mixed methods investigation into the use of non-technical skills by community
      and hospital pharmacists.
AB  - BACKGROUND: Non-technical skills refer to the social and cognitive factors that
      may influence efficient and safe job performance. Non-technical skills are an
      important element of patient safety in a variety of health care disciplines,
      including surgery, anesthesia and nursing. However, the use of non-technical
      skills in pharmacy practice has not yet been fully assessed. OBJECTIVE: To
      examine attitudes toward, and use of, non-technical skills by pharmacy personnel.
      METHODS: A mixed methods approach was used: An attitude survey explored pharmacy
      personnel attitudes towards non-technical skills and inter-professional
      collaboration, with community and hospital pharmacy staff (n = 62). Qualitative
      interviews were then conducted using the critical incident technique, with
      community pharmacists (n = 11). RESULTS: The survey results demonstrated
      differences in the opinions of community and hospital pharmacists on three non
      technical skill constructs: team structure, mutual support, and situation
      monitoring, with community pharmacists reporting significantly more positive
      attitudes about all three constructs. Both groups reported low levels of
      collaboration with primary care physicians. The interviews identified five non
      technical skills as key elements of successful pharmacist performance from the
      interview transcripts: teamwork; leadership; task management; situation
      awareness; decision-making. CONCLUSION: The survey and interviews identified the
      non-technical skills that are important to pharmacists. This represents the first
      step towards the development of a behavioral rating system for training purposes
      that could potentially improve the non-technical skills of pharmacists and
      enhance patient safety.

PMID- 25596069
TI  - Language does not come "in boxes": Assessing discrepancies between adverse drug
      reactions spontaneous reporting and MedDRA(r) codes in European Portuguese.
AB  - BACKGROUND: The description of adverse drug reactions (ADRs) by health care
      professionals (HCPs) can be highly variable. This variation can affect the coding
      of a reaction with the Medical Dictionary for Regulatory Activities
      (MedDRA((r))), the gold standard for pharmacovigilance database entries.
      Ultimately, the strength of a safety signal can be compromised. OBJECTIVE: The
      objective of this study was to assess: 1) participation of different HCPs in ADR
      reporting, and 2) variation of language used by HCPs when describing ADRs, and to
      compare it with the corresponding MedDRA((r)) codes. METHODS: A retrospective
      content analysis was performed, using the database of spontaneous reports
      submitted by HCPs in the region of the Southern Pharmacovigilance Unit, Portugal.
      Data retrieved consisted of the idiomatic description of all ADRs occurring in
      2004 (first year of the Unit activity, n = 53) and in 2012 (n = 350). The
      agreement between the language used by HCPs and the MedDRA((r)) dictionary codes
      was quantitatively assessed. RESULTS: From a total of 403 spontaneous reports
      received in the two years, 896 words describing ADRs were collected. HCPs
      presented different levels of pharmacovigilance participation and ADR idiomatic
      descriptions, with pharmacists providing the greatest overall contribution. The
      agreement between the language used in spontaneous reports and the corresponding
      MedDRA((r)) terms varied by HCP background, with nurses presenting the poorer
      results than medical doctors and pharmacists when considering the dictionary as
      the gold standard in ADRs' language. CONCLUSIONS: Lexical accuracy and semantic
      variations exist between different HCP groups. These differences may interfere
      with the strength of a generated safety signal. Clinical and MedDRA((r))
      terminology training should be targeted to increase not only the frequency, but
      also the quality of spontaneous reports, in accordance with HCPs' experience and
      background.

PMID- 25596072
TI  - Professor Guy H. Sebag (Feb. 11, 1959 - Nov. 28, 2014).

PMID- 25596071
TI  - The kinetics of the hepatitis B surface antigen level after the initiation of
      antiretroviral therapy for hepatitis B virus and human immunodeficiency virus
      coinfected patients.
AB  - BACKGROUND: Hepatic flares (HF), which reflect hepatitis B virus (HBV)-related
      immune reconstitution inflammatory syndrome (IRIS), frequently occur in patients
      with HBV and human immunodeficiency virus (HIV) coinfection after the start of
      antiretoroviral therapy (ART). The rate of hepatitis B envelope antigen (HBeAg)
      and hepatitis B surface antigen (HBsAg) loss is higher for patients with HF after
      the initiation of ART. METHODS: We retrospectively examined the kinetics of the
      HBsAg and HBeAg levels of six HBV/HIV coinfected patients after the commencement
      of ART that included tenofovir. All were male and HBeAg positive. RESULTS: Three
      patients developed HF after the initiation of ART. All subsequently lost HBeAg
      and one of them lost HBsAg after HF. None who did not experience HF lost HBeAg.
      The HBsAg and HBeAg levels remarkably decreased when HF occurred, but the decline
      of HBsAg was very slow in the periods before and after HF. The median decline of
      the HBsAg level at 48 weeks was 2.20 Log IU/mL for patients with HF, but only
      1.00 Log IU/ml for patients without HF. Little decline was seen for either group
      in the median decline of the HBsAg level from 48 weeks to 96 weeks, 0.28 Log
      IU/mL in the HF group and 0.06 Log IU/mL in the non-HF group. CONCLUSION: The
      immune reconstitution of a HBV/HIV coinfected patient plays an important role in
      the clearance of HBV. If HBsAg and HBeAg levels decrease rapidly when HF occurs,
      the hepatic flare would be due to HBV-related IRIS.

PMID- 25596073
TI  - The reasons for knee arthroplasty revisions are incomparable in the different
      arthroplasty registries.
AB  - BACKGROUND: The arthroplasty registries report the survivorship of knee
      arthroplasties and the reasons for revisions. The various registries report
      similar implant survivorships. However, the reasons for the knee revisions have
      not been compared. The aims of this study were to assess the reasons for knee
      arthroplasty revisions from the five valid arthroplasty registries and to
      evaluate whether the reasons for revisions in each registry were similar.
      METHODS: The reported reasons for knee arthroplasty revisions were extracted from
      the arthroplasty registries of Australia, New Zealand, Norway, Sweden, and the
      National Joint Registry for England and Wales. The relevant data were identified
      from each arthroplasty registry's annual reports. RESULTS: All the arthroplasty
      registries collected data for each performed knee arthroplasty revision using a
      specific form. The information provided by the registries varied. The numbers of
      different variables for the revisions were wide-ranging (from 8-33). In addition
      to the different variables, the reported percentages between the registries had
      an extremely wide variation. CONCLUSION: The reasons for knee arthroplasty
      revisions are categorized differently in various arthroplasty registries, and
      there is a wide range of percentages presented. The differences in percentages
      may not be fully explained by the different outcome results in the different
      countries. The heterogeneity of the registries may guide the recording of the
      reasons behind the revisions. There is a definite need to standardize the
      structure of the arthroplasty registries, and to validate the data therein. A
      larger collaboration between the registries is essential.

PMID- 25596074
TI  - A theranostic approach based on the use of a dual boron/Gd agent to improve the
      efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.
AB  - This study aims at developing an innovative theranostic approach for lung tumor
      and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It
      relies on to the use of low density lipoproteins (LDL) as carriers able to
      maximize the selective uptake of boron atoms in tumor cells and, at the same
      time, to quantify the in vivo boron distribution by magnetic resonance imaging
      (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types
      of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung
      metastases were generated by intravenous injection of a Her2+ breast cancer cell
      line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary
      tumor model. After neutron irradiation, tumor growth was followed for 30-40 days
      by MRI. Tumor masses of boron treated mice increased markedly slowly than the
      control group. From the clinical editor: In this article, the authors described
      an improvement to existing boron neutron capture therapy. The dual MRI/BNCT
      agent, carried by LDLs, was able to maximize the selective uptake of boron in
      tumor cells, and, at the same time, quantify boron distribution in tumor and in
      other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor
      cell killing after neutron irradiation.

PMID- 25596076
TI  - Therapeutic applications of nanomedicine in autoimmune diseases: from
      immunosuppression to tolerance induction.
AB  - Autoimmune diseases are chronic, destructive diseases that can cause functional
      disability and multiple organ failure. Despite significant advances in the range
      of therapeutic agents, especially biologicals, limitations of the routes of
      administration, requirement for frequent long-term dosing and inadequate
      targeting options often lead to suboptimal effects, systemic adverse reactions
      and patient non-compliance. Nanotechnology offers promising strategies to improve
      and optimize autoimmune disease treatment with the ability to overcome many of
      the limitations common to the current immunosuppressive and biological therapies.
      Here we focus on nanomedicine-based delivery strategies of biological
      immunomodulatory agents for the treatment of autoimmune disorders including
      psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma,
      multiple sclerosis and type 1 diabetes. This comprehensive review details the
      concepts and clinical potential of novel nanomedicine approaches for inducing
      immunosuppression and immunological tolerance in autoimmune diseases in order to
      modulate aberrant and pathologic immune responses. FROM THE CLINICAL EDITOR: The
      treatment of autoimmune diseases remains a significant challenge. The authors
      here provided a comprehensive review, focusing on the current status and
      potential of nanomedicine-based delivery strategies of immunomodulatory agents
      for the treatment of autoimmune disorders including psoriasis, rheumatoid
      arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis, and type
      1 diabetes.

PMID- 25596075
TI  - Magnetic field-guided cell delivery with nanoparticle-loaded human corneal
      endothelial cells.
AB  - To improve the delivery and integration of cell therapy using magnetic cell
      guidance for replacement of corneal endothelium, here we assess magnetic
      nanoparticles' (MNPs') effects on human corneal endothelial cells (HCECs) in
      vitro. Biocompatible, 50 nm superparamagnetic nanoparticles endocytosed by
      cultured HCECs induced no short- or long-term change in viability or identity.
      Assessment of guidance of the magnetic HCECs in the presence of different magnet
      shapes and field strengths showed a 2.4-fold increase in delivered cell density
      compared to gravity alone. After cell delivery, HCECs formed a functional
      monolayer, with no difference in tight junction formation between MNP-loaded and
      control HCECs. These data suggest that nanoparticle-mediated magnetic cell
      delivery may increase the efficiency of cell delivery without compromising HCEC
      survival, identity or function. Future studies may assess the safety and efficacy
      of this therapeutic modality in vivo. From the clinical editor: The authors show
      in this article that magnetic force facilitates the delivery of human corneal
      endothelial cells loaded by superparamagnetic nanoparticles to cornea, without
      changing their morphology, identity or functional properties. This novel idea can
      potentially have vast impact in the treatment of corneal endothelial dystrophies
      by providing self-endothelial cells after ex-vivo expansion.

PMID- 25596078
TI  - Characterization and evaluation of amphotericin B loaded MDP conjugated
      poly(propylene imine) dendrimers.
AB  - This paper describes a novel strategy for targeted delivery of amphotericin B
      (AmB) to macrophages with muramyl dipeptide (MDP) conjugated multimeric
      poly(propyleneimine) (PPI) dendrimers. Synergistic antiparasitic activity due to
      immunostimulation by multimeric presentation of MDP on dendrimers was
      anticipated. MDP conjugated 5.0G PPI (MdPPI) dendrimers were synthesized and
      characterized. Therapeutic activity and toxicity of dendrimeric formulation of
      AmB (MdPPIA) were compared with marketed formulations of AmB. Highly significant
      (P<0.01) reduction in toxicity was observed in hemolytic toxicity and
      cytotoxicity studies in erythrocytes and J774A.1 macrophage cells, respectively.
      Formulation MdPPIA showed appreciable macrophage targeting potential and higher
      or equivalent antiparasitic activity against parasite infected macrophage cell
      lines and in vivo infection in Balb/c mice. These results suggest the developed
      MDP conjugated dendrimeric formulation of AmB as a promising immunostimulant
      targeted drug delivery system and a safer alternative to marketed formulations.
      From the clinical editor: Parasitic infections remain a significant issue in the
      clinical setting. The authors in this article studied the use of ligand anchored
      dendrimeric formulation of Amphotericin B to target infected macrophages and
      showed reduced toxicity, high anti-leishmanial activity. This may add another
      treatment option to available formulations in the future.

PMID- 25596077
TI  - Promoting filopodial elongation in neurons by membrane-bound magnetic
      nanoparticles.
AB  - Filopodia are 5-10 MUm long processes that elongate by actin polymerization, and
      promote axon growth and guidance by exerting mechanical tension and by molecular
      signaling. Although axons elongate in response to mechanical tension, the
      structural and functional effects of tension specifically applied to growth cone
      filopodia are unknown. Here we developed a strategy to apply tension specifically
      to retinal ganglion cell (RGC) growth cone filopodia through surface
      functionalized, membrane-targeted superparamagnetic iron oxide nanoparticles
      (SPIONs). When magnetic fields were applied to surface-bound SPIONs, RGC
      filopodia elongated directionally, contained polymerized actin filaments, and
      generated retrograde forces, behaving as bona fide filopodia. Data presented here
      support the premise that mechanical tension induces filopodia growth but counter
      the hypothesis that filopodial tension directly promotes growth cone advance.
      Future applications of these approaches may be used to induce sustained forces on
      multiple filopodia or other subcellular microstructures to study axon growth or
      cell migration. From the clinical editor: Mechanical tension to the tip of
      filopodia is known to promote axonal growth. In this article, the authors used
      superparamagnetic iron oxide nanoparticles (SPIONs) targeted specifically to
      membrane molecules, then applied external magnetic field to elicit filopodial
      elongation, which provided a tool to study the role of mechanical forces in
      filopodia dynamics and function.

PMID- 25596080
TI  - Aberrant promoter hypermethylation of p16 gene in endometrial carcinoma.
AB  - Previous studies demonstrated that the loss of function of the p16INK4A gene is
      mainly caused by the hypermethylation of p16 gene promoter; however, whether or
      not it is associated with the incidence of endometrial carcinoma (EC) remains
      unclear. In the current study, we conducted a meta-analysis to investigate the
      effects of p16 gene promoter hypermethylation on the incidence of EC. Detailed
      research publications were searched from Embase, PubMed, and ISI Web of Knowledge
      for composition in English or Chinese. The pooled data were collected and
      analyzed by Review Manager 5.2. Odds ratios (ORs) were calculated and summarized
      respectively. Six eligible studies, including 261 patients were selected and
      analyzed. The pooled OR was 0.42, test for overall effect, Z = 10.19, P < 0.0001,
      indicating that p16 gene promoter hypermethylation was significantly correlated
      with the EC patients. The results of our study strongly suggest that p16 gene
      promoter hypermethylation is correlated with an increased risk of EC. P16 gene
      promoter hypermethylation plays a critical role in endometrial carcinogenesis.

PMID- 25596079
TI  - Analysis of human innate immune responses to PRINT fabricated nanoparticles with
      cross validation using a humanized mouse model.
AB  - Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of
      inherent cytotoxic or immunostimulatory properties. Therefore, determining
      baseline immune responses to nanomaterials is of utmost importance when designing
      human therapeutics. We characterized the response of human immune cells to
      hydrogel NPs fabricated using Particle Replication in Non-wetting Templates
      (PRINT) technology. We found preferential NP uptake by primary CD14(+) monocytes,
      which was significantly reduced upon PEGylation of the NP surface. Multiplex
      cytokine analysis of NP treated primary human peripheral blood mononuclear cells
      suggests that PRINT based hydrogel NPs do not evoke significant inflammatory
      responses nor induce cytotoxicity or complement activation. We furthered these
      studies using an in vivo humanized mouse model and similarly found preferential
      NP uptake by human CD14(+) monocytes without systemic inflammatory cytokine
      responses. These studies suggest that PRINT hydrogel particles form a desirable
      platform for vaccine and drug delivery as they neither induce inflammation nor
      toxicity. From the clinical editor: The authors here fabricated hydrogel nanorods
      using the PRINT (Particle Replication In Nonwetting Templates) fabrication
      process. They tested the interaction of human immune cells with these particles
      and found no immunoreactivity. This finding would suggest that monodisperse PRINT
      particles of identical shape and size could serve a variety of clinical
      applications.

PMID- 25596081
TI  - Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and
      literature review.
AB  - The development of colorectal cancer (CRC) spans about 5-10 years, making early
      detection and prevention beneficial to the survival of CRC patients. To address
      inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase
      (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta
      analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were
      included in the meta-analysis after screening 120 articles. The following items
      were collected from each study: author, published year, country, patient gender,
      MGMT methylation status, and patients' disease progression. Pooled hazard ratios
      and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or
      random effect models depending on the heterogeneity between studies. The overall
      survival of CRC patients was found not to be significantly associated with MGMT
      methylation. Further subgroup analysis showed that the frequency of MGMT
      methylation was significantly higher in CRC than in normal tissues (p < 0.00001).
      MGMT promoter in CRC patients was more frequently methylated than in adenoma
      patients. In addition, MGMT methylation was significantly increased in adenoma
      than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central
      to the development of cancer that involves a stepwise carcinogenesis of normal
      adenoma carcinoma cascade. However, MGMT methylation is not associated with the
      prognosis of CRC.

PMID- 25596082
TI  - Induction of S phase arrest and apoptosis by ethyl acetate extract from
      Tetrastigma hemsleyanum in human hepatoma HepG2 cells.
AB  - Tetrastigma hemsleyanum, a rare and endangered medicinal plant, has attracted
      much attention due to antitumor and immunomodulatory activities. In this study,
      the effect and mechanism of ethyl acetate extract from T. hemsleyanum (EET) on
      cell cycle and apoptosis in human hepatoma HepG2 cells were investigated. Twenty
      five to 200 MUg/mL of EET were found to have the antiproliferation effect toward
      HepG2 cells determined by MTT assay. The morphology of EET-treated HepG2 cells
      showed evidence of apoptosis that included blebbing and chromatin condensation,
      nucleic fragmentation, and so on. The DNA laddering assay confirmed that DNA
      fragmentation had occurred during late apoptosis. The cell-cycle analysis
      indicated that EET was able to induce S phase arrest and typical subdiploid peak
      in a dose- and time-dependent manner. The apoptosis rate of 200 MUg/mL treatment
      for 24 h was 42.24 +/- 4.90%. The protein expression of Bax and P53 was increased
      after treatment, while that of Bcl2 was significantly decreased in a dose
      dependent manner, which suggested that a high Bax/Bcl2 ratio and an upregulated
      P53 might contribute to the pro-apoptotic activity of EET via the mitochondria
      dependent pathway. The protein expression of cyclin-dependent kinase 1 (CDK1) was
      decreased in EET-treated HepG2 cells, suggesting that EET evoked S phase arrest
      possibly through the downregulation of cyclin A-CDK1 complex. In conclusion, the
      cytotoxicity on HepG2 cells induced by EET is a result of both cell-cycle arrest
      and apoptosis. Thus, it may have therapeutic potential for the treatment of liver
      cancer.

PMID- 25596083
TI  - MicroRNA-34a expression is predictive of recurrence after radiofrequency ablation
      in early hepatocellular carcinoma.
AB  - The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency
      ablation (RFA) is mainly associated with tumor recurrence. So far, no tissue
      biomarker of recurrence has been confirmed in biopsy specimens. Previous studies
      have reported that aberrant expression of microRNA-34a (miR-34a) is involved in
      oncogenesis and progression of HCC. The aim of this study was to investigate the
      prognostic value of tissue miR-34a expression in patients with HCC treated with
      RFA. Patients with early-stage single-nodule HCC treated with RFA were included,
      and tissue expression of miR-34a were assessed by quantitative reverse
      transcription polymerase chain reaction. Main clinical endpoints were overall and
      early recurrence. The Kaplan-Meier method was used to plot recurrence curves and
      univariable and multivariable Cox regression analyses were performed to assess
      independent predictive factors for recurrence. Of 120 patients, recurrence
      occurred in 67 patients (55.8 %) with a median follow-up of 31 months. Forty-one
      patients (34.2 %) recurred within 2 years after RFA. The median miR-34a level was
      0.87 (range 0.06-21.54). Low miR-34a level was associated with larger tumor size
      (P = 0.033) and higher serum alpha-fetoprotein (AFP) level (P = 0.004). When
      analyzed with a Cox regression model, the two independent predictive factors for
      overall recurrence were high serum AFP level (hazard ratio [HR] = 1.21; 95 %
      confidence interval [CI] = 1.04-1.36; P = 0.039) and low miR-34a level (HR =
      1.44; 95 % CI = 1.13-1.72; P = 0.011). The expression of miR-34a was also an
      independent predictive factor for early recurrence (HR = 1.49; 95 % CI = 1.15
      1.79; P = 0.008). Taken together, this study suggests that the expression of miR
      34a in HCC biopsy specimens has an independent predictive value of early
      recurrence after RFA.

PMID- 25596084
TI  - Association between six genetic variants of IL-17A and IL-17F and cervical cancer
      risk: a case-control study.
AB  - We conducted a case-control study to estimate association between six common
      single nucleotide polymorphisms (SNPs) and risk of cervical cancer and evaluate
      the interaction between IL-17 gene polymorphisms and environmental factors in
      cervical cancer patients. This study included 264 consecutive primary cervical
      cancer patients and 264 age-matched controls. The genotypes of IL-17A rs2275913,
      rs3748067, and rs3819025 and IL-17A rs763780, rs9382084, and rs1266828 were
      analyzed using polymerase chain reaction-restriction fragment length of
      polymorphism (PCR-RFLP) assay. By logistic regression analysis, we found that
      individuals with AA genotype of rs2275913 were correlated with increased risk of
      cervical cancer when compared with GG genotype, and the odds ratio (OR) (95 %
      confidence interval (CI)) for AA genotype was 2.34 (1.24-4.49). By stratified
      analysis, individuals with AA genotype of rs2275913 were significantly associated
      with increased risk of cervical cancer in HPV-16- or HPV-18-infected patients
      when compared with GG genotype, and the OR (95 % CI) was 4.11 (1.14-22.33). In
      this case-control study, we suggest that rs2275913 may play an important role in
      the development of cervical cancer, especially in HPV-16- or HPV-18-infected
      patients.

PMID- 25596085
TI  - Defective Beclin-1 and elevated hypoxia-inducible factor (HIF)-1alpha expression
      are closely linked to tumorigenesis, differentiation, and progression of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis.
      Autophagy and hypoxia have been involved in HCC tumorigenesis. In the present
      study, we examined the relationship between Beclin-1 expression and hypoxia
      inducible factor (HIF)-1alpha expression in HCC by immunohistochemistry on 65
      tumor specimens. Their correlations with clinicopathological features were also
      explored. There was a loss of Beclin-1 protein expression in 49.2 % of HCC.
      Beclin-1 expression was only significantly correlated with virus infection status
      (p = 0.025) and marginally associated with HCC grade (p = 0.057). Forty-two
      tumors (64.6 %) showed high HIF-1alpha expression, and it was significantly
      associated with large tumor size (p = 0.003), multifocal tumors (p = 0.038), and
      advanced stage (p = 0.043). Beclin-1 expression was significantly associated with
      HIF-1alpha expression (p = 0.001). HCC cases were further stratified according to
      their hypoxia status into hypoxic and normoxic groups. In the hypoxic group,
      Beclin-1 expression was negatively correlated with HCC high tumor grade (p <
      0.001), advanced stage (p = 0.013), large size (p = 0.002), and multifocal tumors
      (p = 0.047). In the normoxic group, no significant relations between Beclin-1
      expression and any of the clinicopathological parameters were identified. Our
      findings that reduced Beclin-1 and high HIF-1alpha expression are associated with
      the development and progression of HCC may provide molecular therapeutic targets
      toward inhibiting HCC development and progression.

PMID- 25596086
TI  - FasL -844T/C and Fas -1377G/A: mutations of pulmonary adenocarcinoma in South
      China and their clinical significances.
AB  - Apoptosis is an important mechanism of malignant tumor formation and progression.
      Single nucleotide polymorphisms (SNPs) located within cell death genes may
      influence cancer risk. We explored the relationship between FasL -844T/C and/or
      Fas -1377G/A SNPs and pulmonary adenocarcinoma (AD). Two hundred seventy-five
      patients with pulmonary AD of South China admitted into Zhejiang Cancer Hospital
      from July 2007 to October 2011 were randomly selected, and their
      clinicopathological data were collected at the same time. Two hundred ninety
      seven cases of healthy individuals were selected as control. FasL -844T/C and Fas
      -1377G/A SNPs were detected by PCR-RFLP technique to evaluate the relationships
      between these two SNPs and pulmonary AD. Age, FasL -844 and Fas -1377 SNPs were
      associated with increased risk of pulmonary AD susceptibility in main effect
      analysis. FasL -844CC and Fas -1377 AA were associated with an increased risk for
      the development of pulmonary AD only in age <60 years people, but not in those
      >=60 years. FasL -844CC genotype was associated with an increased risk for
      pulmonary AD (adjusted OR = 2.010, 95 % CI 1.196-3.379, P = 0.008) compared with
      TT genotype. However, Fas -1377 AA was a risk factor only when FasL -844 genotype
      was CC. Fas -1377 genotypes showed significant effect modification of pulmonary
      AD risk by FasL -844 genotype with test of the interaction term adjusting for
      age, gender, and FasL -844 SNP. Fas -1377G/A was not associated with the
      clinicopathological factors, while FasL -844C/T was associated with tumor stage
      and lymph node metastasis in age >=60 years people and tumor stage in those <60
      years. In conclusion, FasL -844 SNP is associated with the susceptibility of
      pulmonary AD in age <60 years people. Fas -1377 SNP may modify the association of
      FasL -844 SNP with the risk of pulmonary AD. FasL -844 genotype plays an
      important role in the occurrence and progression of pulmonary AD.

PMID- 25596087
TI  - Nicotinamide induces apoptosis of F9 mouse teratocarcinoma stem cells by
      downregulation of SATB1 expression.
AB  - The aim of this study was to decide whether nicotinamide (NA) could induce
      apoptosis of F9 mouse teratocarcinoma stem cells (MF9) by downregulation of
      special AT-rich sequence binding protein 1 (SATB1) expression. We used different
      concentrations of NA (0, 1.5, 2, and 2.5 mmol/L) to treat MF9 cells and analyze
      SATB1 expression by RT-qPCR and Western blotting; in addition, the cell
      proliferation was detected in a microplate reader with Cell Counting Kit-8 (CCK
      8), and the cell cycle and apoptosis were analyzed using flow cytometry. We found
      that the expression of SATB1 was decreased significantly in NA-treated groups
      than in the control group, and its expression level was inversely related to the
      NA concentration. In addition, CCK-8 analysis showed that NA significantly
      inhibited the proliferation of MF9 cells, and flow cytometry showed that NA
      blocked MF9 cells to G1 phase and significantly promoted apoptosis in any treated
      groups. To confirm the results, we constructed small interference RNA (siRNA)
      targeting at mouse SATB1 and transferred into MF9 cells. The results indicated
      that the expression of SATB1 in both mRNA and protein levels was significantly
      decreased after cells transferred with siRNA sequence for 48 h, the proliferation
      of MF9 cells was significantly inhibited, and most of MF9 cells were blocked at
      G1 phase, and the apoptosis rate was increased obviously. The results showed that
      NA could inhibit the proliferation and induce apoptosis of MF9 cells. These
      findings might be used as an efficient candidate for teratocarcinoma therapy.

PMID- 25596088
TI  - Urinary parameters predictive and electrolyte disturbances of cisplatin-induced
      acute renal associated with cancer as a critical target of the chemotherapeutic
      agent in patients with solid tumors.
AB  - Cisplatin (CP) is a remarkably effective Pt-based anticancer drug, but it also
      exhibits severe toxic side effects, including nephrotoxicity and ototoxicity, and
      CP nephrotoxicity is a major constraint for the treatment of solid tumors. This
      study was designed to evaluate the electrolyte and biochemical changes in dogs
      with acute kidney injury (acute renal failure) following administration of CP as
      a chemotherapeutic agent to exhibit broad efficacy in solid tumors. A total of 10
      adult male dogs were selected (treated dogs = 7 and control dogs = 3). Cisplatin
      treated animals were received 0.75 mg/kg via intravenous for 5 consecutive days.
      Urine and blood samples on days 0 (pre-dosing), 1, 2, 3, 4, 7, 10, 14, and 28
      (post-dosing) were collected. For tracking the signs of toxicity with cisplatin,
      clinical examination was performed for 2 times a day. Serum samples were assayed
      urea, creatinine, sodium, chloride, potassium, calcium, phosphorus, and urine
      samples were used to measure creatinine. Serum creatinine levels indicating renal
      function (glomerular filtration rate) was 0.66 and 0.94 mg/dL in day 0,
      respectively, in treatment and control animals. After day 2, a significant change
      in creatinine was observed in treatment animals. On the end day of the study
      control and treatments, creatinine was measured with mean of 1.35 and 1.00 mg/dL,
      respectively. Electrolyte disturbances were observed after several days of
      cisplatin administration including changes in levels of sodium, potassium,
      phosphorus, calcium, and chloride. Clinical observations also identified CP
      toxicity. This study for the first time showed that compensation electrolyte
      abnormalities in dogs following administration of cisplatin is essential to
      prevent deaths by daily monitoring and measurement of electrolytes in patients.
      This may be advantageous if repetitive cycles of chemotherapy or subsequent
      administration of high dose chemotherapy were planned.

PMID- 25596089
TI  - Insulin-like growth factor 1 promotes growth of gastric cancer by inhibiting
      foxo1 nuclear retention.
AB  - Gastric cancer (GC) is the fourth most common malignant human cancer. So far, the
      molecular mechanisms underlying the tumorigenesis of GC are not completely
      understood. Here, we reported significantly higher levels of serum insulin-like
      growth factor (IGF)-1 in GC patients and significantly higher levels of
      phosphorylated IGF-1 receptor (IGF-1R) in the GC specimen. Moreover, IGF-1
      induced phosphorylation of IGF-1R and then phosphorylation of its downstream
      factor Akt in the GC cells. Further, IGF-1/Akt-induced forkhead box protein O1
      (FoxO1) nuclear exclusion, but not IGF-1/Akt-induced mTOR phosphorylation, was
      essential for the augment in GC cell growth. Together, IGF-1/Akt/FoxO1 regulatory
      machinery appears to be a previously unappreciated signaling axis involved in the
      carcinogenesis of GC.

PMID- 25596090
TI  - Altered tyrosine metabolism and melanization complex formation underlie the
      developmental regulation of melanization in Manduca sexta.
AB  - The study of hemolymph melanization in Lepidoptera has contributed greatly to our
      understanding of its role in insect immunity. Manduca sexta in particular has
      been an excellent model for identifying the myriad components of the
      phenoloxidase (PO) cascade and their activation through exposure to pathogen
      associated molecular patterns (PAMPs). However, in a process that is not well
      characterized or understood, some insect species rapidly melanize upon wounding
      in the absence of added PAMPs. We sought to better understand this process by
      measuring wound-induced melanization in four insect species. Of these, only
      plasma from late 5th instar M. sexta was unable to melanize, even though each
      contained millimolar levels of the putative melanization substrate tyrosine
      (Tyr). Analysis of Tyr metabolism using substrate-free plasmas (SFPs) from late
      5th instar larvae of each species showed that only M. sexta SFP failed to
      melanize with added Tyr. In contrast, early instar M. sexta larvae exhibited
      wound-induced melanization and Tyr metabolism, and SFPs prepared from these
      larvae melanized in the presence of Tyr. Early instar melanization in M. sexta
      was associated with the formation of a high mass protein complex that could be
      observed enzymatically in native gels or by PO-specific immunoblotting. Topical
      treatment of M. sexta larvae with the juvenile hormone (JH) analog methoprene
      delayed pupation and increased melanizing ability late in the instar, thus
      linking development with immunity. Our results demonstrate that melanization
      rates are highly variable in Lepidoptera, and that developmental stage can be an
      important factor for melanization within a species. More specifically, we show
      that the physiological substrate for melanization in M. sexta is Tyr, and that
      melanization is associated with the formation of a PO-containing protein complex.

PMID- 25596091
TI  - Glandular beta-glucosidases in juvenile Chrysomelina leaf beetles support the
      evolution of a host-plant-dependent chemical defense.
AB  - Plant-feeding insects are spread across the entire plant kingdom. Because they
      chew externally on leaves, leaf beetle of the subtribe Chrysomelina sensu stricto
      are constantly exposed to life-threatening predators and parasitoids. To counter
      these pressures, the juveniles repel their enemies by displaying glandular
      secretions that contain defensive compounds. These repellents can be produced
      either de novo (iridoids) or by using plant-derived precursors. The autonomous
      production of iridoids pre-dates the evolution of phytochemical-based defense
      strategies. Both strategies include hydrolysis of the secreted non-toxic
      glycosides in the defensive exudates. By combining in vitro as well as in vivo
      experiments, we show that iridoid de novo producing as well as sequestering
      species rely on secreted beta-glucosidases to cleave the pre-toxins. Our
      phylogenetic analyses support a common origin of chrysomeline beta-glucosidases.
      The kinetic parameters of these beta-glucosidases demonstrated substrate
      selectivity which reflects the adaptation of Chrysomelina sensu stricto to the
      chemistry of their hosts during the course of evolution. However, the functional
      studies also showed that the broad substrate selectivity allows building a
      chemical defense, which is dependent on the host plant, but does not lead to an
      "evolutionary dead end".

PMID- 25596092
TI  - Positive feedback regulation of prothoracicotropic hormone secretion by
      ecdysteroid--a mechanism that determines the timing of metamorphosis.
AB  - When insect larvae have fully grown, prothoracicotropic hormone (PTTH) is
      released from the brain, triggering the initiation of metamorphic development
      through stimulation of ecdysteroid secretion by the prothoracic glands. The
      present study analyzes the mechanism that regulates the occurrence of this PTTH
      surge. In the silkworm Bombyx mori, the PTTH surge occurs on day 6 of the fifth
      instar and is preceded by a small rise in hemolymph ecdysteroid titer, which
      occurs late on day 5. We therefore hypothesized that this rise of ecdysteroid
      titer is involved in the induction of the PTTH surge. To test this hypothesis,
      two experiments were conducted. First, a small amount of 20-hydroxyecdysone was
      injected on day 4, two days before the expected day of the PTTH surge, to
      simulate the small rise in hemolymph ecdysteroid titer on day 5. This injection
      led to a precocious surge of PTTH the next day. Next, the hemolymph ecdysteroid
      titer on day 5 was artificially lowered by injecting ecdysteroid-22-oxidase,
      which inactivates 20-hydroxyecdysone. After this treatment, the PTTH surge did
      not occur on day 6 in 80% of the animals. These results indicate that a small
      rise of the hemolymph ecdysteroid titer plays a critical role in the induction of
      the PTTH surge. Since basal ecdysteroidogenic activity of the prothoracic glands
      increases with larval growth, a circulating level of ecdysteroids may convey
      information about larval maturity to the brain, to coordinate larval growth and
      metamorphosis. This is the first report in invertebrates to demonstrate positive
      feedback regulation of the surge of a tropic hormone by a downstream steroid
      hormone. 

PMID- 25596093
TI  - Diversity, pharmacology and synthesis of bergenin and its derivatives: potential
      materials for therapeutic usages.
AB  - Bergenin, a natural secondary metabolite, has been isolated from different parts
      of a number of plants. It is one of active ingredients in herbal and Ayurvedic
      formulations. It exhibits antiviral, antifungal, antitussive, antiplasmodial,
      antiinflammatory, antihepatotoxic, antiarrhythmic, antitumor, antiulcerogenic,
      antidiabetic and wound healing properties. It has been analyzed and estimated in
      different plant extracts, blood and drug samples using chromatographic
      techniques, and pharmacokinetic studies have been made. Several bergenin
      derivatives were isolated and/or synthesized and were found to possess
      pharmacological activities. Total synthesis of bergenin and its derivatives were
      reported. This review article covers literature on bergenin and its derivatives
      until 2013. Ethnomedicinal value of bergenin containing plant materials is also
      highlighted. This comprehensive review provides information on the potentiality
      of bergenin and its derivatives for therapeutic usages. 

PMID- 25596094
TI  - Amaryllidaceae alkaloids from the bulbs of Lycoris radiata with cytotoxic and
      anti-inflammatory activities.
AB  - Four new Amaryllidaceae alkaloids, (+)-1-hydroxy-ungeremine (1), (+)-6beta-acetyl
      8-hydroxy-9-methoxy-crinamine (2), (+)-2-hydroxy-8-demethyl-homolycorine-alpha-N
      oxide (3), (+)-N-methoxylcarbonyl-2-demethyl-isocorydione (4), together with two
      known compounds, (+)-6beta-acetyl-crinamine (5) and 8-demethyl-homolycorine-alpha
      N-oxide (6) were isolated from the ethanol extract of the bulbs of Lycoris
      radiata. Structural elucidation of all the compounds were performed by spectral
      methods such as 1D and 2D ((1)H-(1)H COSY, HMQC, and HMBC) NMR spectroscopy, in
      addition to high resolution mass spectrometry. All the isolated alkaloids were in
      vitro evaluated for their cytotoxic activities against eight tumor cell lines
      (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2 and SK-OV-3) and anti
      inflammatory activities against Cox-1 and Cox-2. As a result, alkaloids 1 and 4
      exhibited significant cytotoxic activities against all tested tumor cell lines
      except against BEN-MEN-1. Additionally, alkaloids 1 and 4 possessed selective
      inhibition of Cox-2 comparable with the standard drug NS-398 (>90%). 

PMID- 25596095
TI  - Fructus Psoraleae contains natural compounds with potent inhibitory effects
      towards human carboxylesterase 2.
AB  - Fructus Psoraleae (FP) is an edible Chinese herbal which is widely used in Asia
      for the treatment of various diseases including asthma, diarrhea, and
      osteoporosis. This study aimed to investigate the inhibitory effects of the crude
      ethanol extract from FP on human carboxylesterase 2 (hCE2), as well as to
      identity and characterize the naturally occurring inhibitors of hCE2 in FP. Our
      results demonstrated that the ethanol extract of FP displayed potent inhibitory
      effects towards hCE2, while five major bioactive constitutes in FP were
      efficiently identified by LC-DAD-ESI-MS/MS, with the aid of LC-based activity
      profiling. The identified bioactive compounds including neobavaisoflavone,
      isobavachalcone, bavachinin, corylifol A and bakuchiol were found to be naturally
      occurring potent inhibitors of hCE2, with low Ki values ranging from 0.62MUM to
      3.89MUM. This is the first report of the chemical constitutes in FP as potent
      inhibitors of hCE2. 

PMID- 25596096
TI  - The propre-save study: effects of probiotics and prebiotics alone or combined on
      necrotizing enterocolitis in very low birth weight infants.
AB  - OBJECTIVE: To test the efficacy of probiotic and prebiotic, alone or combined
      (synbiotic), on the prevention of necrotizing enterocolitis (NEC) in very low
      birth weight (VLBW) infants. STUDY DESIGN: A prospective, randomized, controlled
      trial was conducted at 5 neonatal intensive care units in Turkey. VLBW infants (n
      = 400) were assigned to a control group and 3 study groups that were given
      probiotic (Bifidobacterium lactis), prebiotic (inulin), or synbiotic
      (Bifidobacterium lactis plus inulin) added to breastmilk or formula for a maximum
      of 8 weeks before discharge or death. The primary outcome was NEC (Bell stage
      >=2). RESULTS: The rate of NEC was lower in probiotic (2.0%) and synbiotic (4.0%)
      groups compared with prebiotic (12.0%) and placebo (18.0%) groups (P < .001). The
      times to reach full enteral feeding were faster (P < .001), the rates of clinical
      nosocomial sepsis were lower (P = .004), stays in the neonatal intensive care
      unit were shorter, (P = .002), and mortality rates were lower (P = .003) for
      infants receiving probiotics, prebiotics, or synbiotic than controls. The use of
      antenatal steroid (OR 0.5, 95% CI 0.3-0.9) and postnatal probiotic (alone or in
      synbiotic) (OR 0.5, 95% CI 0.2-0.8) decreased the risk of NEC, and maternal
      antibiotic exposure increased this risk (OR 1.9, 95% CI 1.1-3.6). CONCLUSIONS: In
      VLBW infants, probiotic (Bifidobacterium lactis) and synbiotic (Bifidobacterium
      lactis plus inulin) but not prebiotic (inulin) alone decrease NEC.

PMID- 25596097
TI  - Physical exercise recommendations improve postural changes found in children and
      adolescents with cystic fibrosis: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate postural changes and the distribution of plantar pressures
      in patients with cystic fibrosis (CF). We also sought to evaluate the effects of
      an educational guideline for physical activity on body posture in children and
      adolescents with CF. STUDY DESIGN: This was a 2-phase study of individuals
      between age 7 and 20 years. Phase I was a cross-sectional study in which healthy
      subjects were selected for postural evaluation and baropodometry, aiming to
      perform a later comparison with patients with CF. In phase II, we performed a
      randomized controlled clinical trial to assess the influence of the exercise
      guideline on the postural changes. Patients were assigned to 2 groups: control
      and intervention. The intervention consisted of a handbook with instructions for
      aerobic exercise and stretching. Main outcomes were postural abnormalities,
      plantar pressure distribution, and lung function. RESULTS: In phase I, 34
      patients with CF and 34 healthy matched individuals were included. No significant
      baseline differences were identified. Children with CF presented more postural
      deviations compared with healthy subjects (P < .05), as to alignment of the head,
      shoulder girdle, and pelvis, increased cervical lordosis, and lateral chest
      distance. In phase II (n = 34), there were no baseline differences between
      groups. The intervention caused (P < .05) a decrease in cervical lordosis,
      thoracic kyphosis, lumbar lordosis, lateral chest distance, and abdominal
      protrusion, as well as in the baropodometric mean pressure and contact area.
      CONCLUSIONS: Children and adolescents with CF present postural changes when
      compared with healthy individuals. The educational guideline for exercise
      practice helped to improve posture, preventing the progression of some postural
      disorders.

PMID- 25596099
TI  - Exhaled carbon dioxide in healthy term infants immediately after birth.
AB  - OBJECTIVE: To measure exhaled carbon dioxide (ECO2) in term infants immediately
      after birth. STUDY DESIGN: Infants >37 weeks gestation born at The Royal Women's
      Hospital, Melbourne, Australia were eligible. A combined flow sensor and
      mainstream carbon dioxide (CO2) analyzer was placed in series proximal to a
      facemask to measure ECO2 and tidal volumes in the first 120 seconds after birth.
      RESULTS: Term infants (n = 20) with a mean (SD) birth weight of 2976 (697) g and
      gestational age of 38 (2) weeks were included. Infants took a median (range) 3 (1
      8) breaths before ECO2 was detected. The median (range) of maximum ECO2 was 51
      (40-73) mm Hg at 70 (21-106) seconds after birth. Within the first 10 breaths,
      CO2 increased from 0-27 (22-34) mm Hg. The median (IQR) tidal volume during the
      breaths without CO2 was 1.2 (0.8-3.1) mL/kg compared with 7.3 (3.2-10.9) mL/kg
      during the first 10 breaths where CO2 was exhaled. CONCLUSIONS: The first breaths
      for an infant after birth did not contain ECO2. With aeration of the distal gas
      exchange regions, tidal volume and ECO2 significantly increased. ECO2 can be used
      to monitor lung aeration immediately after birth.

PMID- 25596098
TI  - Children with Down syndrome are high-risk for severe respiratory syncytial virus
      disease.
AB  - OBJECTIVE: To assess Down syndrome as an independent risk factor for respiratory
      syncytial virus (RSV) hospitalization in children younger than 3 years of age and
      to evaluate illness severity. STUDY DESIGN: A retrospective cohort study of
      children enrolled in the military health system database was conducted. The
      effect of Down syndrome on RSV hospitalization was assessed by Cox proportional
      hazards model, while we controlled for risk factors. Disease severity was
      assessed by length of hospital stay, need for respiratory support, and age at
      hospitalization. RESULTS: The study included 633 200 children and 3 209 378
      person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs
      2.8% in children without Down syndrome. Down syndrome had a greater adjusted
      hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI
      2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for
      patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages
      24-36 months. The median (IQR) length of stay of children with and without Down
      syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down
      syndrome had a greater risk of requiring respiratory support (relative risk 5.5;
      95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and
      without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P <
      .001). CONCLUSIONS: Down syndrome is independently associated with an increased
      risk for RSV hospitalization. Children with Down syndrome are older at time of
      RSV hospitalization and have more severe RSV illness than children without Down
      syndrome. This increased risk for hospitalization continues beyond 24 months.

PMID- 25596101
TI  - Nonsuicidal self-injury among youth.

PMID- 25596100
TI  - Health literacy affects likelihood of radiology testing in the pediatric
      emergency department.
AB  - OBJECTIVE: To test the hypothesis that the effect of race/ethnicity on decreased
      radiologic testing in the pediatric emergency department (ED) varies by caregiver
      health literacy. STUDY DESIGN: This was a secondary analysis of a cross-sectional
      study of caregivers accompanying children <= 12 years to a pediatric ED.
      Caregiver health literacy was measured using the Newest Vital Sign. A blinded
      chart review determined whether radiologic testing was utilized. Bivariate and
      multivariate analyses, adjusting for ED triage level, child insurance, and
      chronic illness were used to determine the relationship between race/ethnicity,
      health literacy, and radiologic testing. Stratified analyses by caregiver health
      literacy were conducted. RESULTS: Five hundred four caregivers participated; the
      median age was 31 years, 47% were white, 37% black, 10% Hispanic, and 49% had low
      health literacy. Black race and low health literacy were associated with less
      radiologic testing (P < .01). In stratified analysis, minority race was
      associated with less radiologic testing only if a caregiver had low health
      literacy (aOR 0.5; 95% CI 0.3-0.9), and no difference existed in those with
      adequate health literacy (aOR 0.7; 95% CI 0.4-1.3). CONCLUSIONS: Caregiver low
      health literacy modifies whether minority race/ethnicity is associated with
      decreased radiologic testing, with only children of minority caregivers with low
      health literacy receiving fewer radiologic studies. Future interventions to
      eliminate disparities in healthcare resource utilization should consider health
      literacy as a mutable factor.

PMID- 25596102
TI  - Prematurity and perinatal antibiotics: a tale of two factors influencing
      development of the neonatal gut microbiota.

PMID- 25596103
TI  - Pressure-flow characteristics of normal and disordered esophageal motor patterns.
AB  - OBJECTIVE: To perform pressure-flow analysis (PFA) in a cohort of pediatric
      patients who were referred for diagnostic manometric investigation. STUDY DESIGN:
      PFA was performed using purpose designed Matlab-based software. The pressure-flow
      index (PFI), a composite measure of bolus pressurization relative to flow and the
      impedance ratio, a measure of the extent of bolus clearance failure were
      calculated. RESULTS: Tracings of 76 pediatric patients (32 males; 9.1 +/- 0.7
      years) and 25 healthy adult controls (7 males; 36.1 +/- 2.2 years) were analyzed.
      Patients mostly had normal motility (50%) or a category 4 disorder and usually
      weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy
      controls defined reference ranges for PFI <=142 and impedance ratio <=0.49.
      Pediatric patients with pressure-flow (PF) characteristics within these limits
      had normal motility (62%), most patients with PF characteristics outside these
      limits also had an abnormal Chicago Classification (61%). Patients with high PFI
      and disordered motor patterns all had esophagogastric junction outflow
      obstruction. CONCLUSIONS: Disordered PF characteristics are associated with
      disordered esophageal motor patterns. By defining the degree of over
      pressurization and/or extent of clearance failure, PFA may be a useful adjunct to
      esophageal pressure topography-based classification.

PMID- 25596104
TI  - Childhood wrist circumference is not a predictor of insulin resistance in
      adulthood.
AB  - We sought to determine whether childhood wrist circumference predicts insulin
      resistance in adulthood. Measures were taken in prepubertal children and then
      approximately 30 years later in the same subjects as adults. Our findings suggest
      that wrist circumference in childhood is not a predictor of insulin resistance in
      adulthood.

PMID- 25596105
TI  - Association of fatty acid ethyl esters in meconium and cognitive development
      during childhood and adolescence.
AB  - OBJECTIVE: To examine associations between amounts of fatty acid ethyl esters
      (FAEEs) in meconium and cognitive development in school-aged children exposed to
      alcohol and drugs in utero. STUDY DESIGN: A secondary analysis of a prospective
      cohort of children, primarily African American and of low socioeconomic status,
      that was recruited at birth. FAEEs were quantified with gas chromatography via a
      flame ionization detector. Meconium was analyzed for FAEEs in 216 newborns; 191
      of these infants were assessed for IQ at ages 9, 11, and 15 years with the
      Wechsler Intelligence Scales for Children-Fourth Edition. RESULTS: Longitudinal
      mixed model analyses indicated that, after we controlled for maternal and child
      covariates, greater concentrations of FAEEs (ethyl myristate, ethyl oleate, ethyl
      linoleate, and ethyl linolenate) were associated with lower Wechsler Intelligence
      Scales for Children-Fourth Edition Verbal Comprehension Index, Working Memory
      Index, and Full-Scale IQ scores. Associations of FAEEs with Verbal Comprehension
      Index, Working Memory Index, and Full-Scale IQ did not vary over time. No
      associations of FAEEs with Perceptual Reasoning and Processing Speed Indices were
      found. CONCLUSION: Elevated levels of FAEEs in meconium are potential markers for
      identifying newborns at risk for poor cognitive development related to prenatal
      alcohol exposure.

PMID- 25596106
TI  - Evaluating the impact of a Canadian national anatomy and radiology contouring
      boot camp for radiation oncology residents.
AB  - BACKGROUND: Radiation therapy treatment planning has advanced over the past 2
      decades, with increased emphasis on 3-dimensional imaging for target and organ-at
      risk (OAR) delineation. Recent studies suggest a need for improved resident
      instruction in this area. We developed and evaluated an intensive national
      educational course ("boot camp") designed to provide dedicated instruction in
      site-specific anatomy, radiology, and contouring using a multidisciplinary (MDT)
      approach. METHODS: The anatomy and radiology contouring (ARC) boot camp was
      modeled after prior single-institution pilot studies and a needs-assessment
      survey. The boot camp incorporated joint lectures from radiation oncologists,
      anatomists, radiologists, and surgeons, with hands-on contouring instruction and
      small group interactive seminars using cadaveric prosections and correlative
      axial radiographs. Outcomes were evaluated using pretesting and posttesting,
      including anatomy/radiology multiple-choice questions (MCQ), timed contouring
      sessions (evaluated relative to a gold standard using Dice similarity metrics),
      and qualitative questions on satisfaction and perceived effectiveness. Analyses
      of pretest versus posttest scores were performed using nonparametric paired
      testing. RESULTS: Twenty-nine radiation oncology residents from 10 Canadian
      universities participated. As part of their current training, 29%, 75%, and 21%
      receive anatomy, radiology, and contouring instruction, respectively. On posttest
      scores, the MCQ knowledge scores improved significantly (pretest mean 60% vs
      posttest mean 80%, P<.001). Across all contoured structures, there was a 0.20
      median improvement in students' average Dice score (P<.001). For individual
      structures, significant Dice improvements occurred in 10 structures. Residents
      self-reported an improved ability to contour OARs and interpret radiographs in
      all anatomic sites, 92% of students found the MDT format effective for their
      learning, and 93% found the boot camp more effective than educational sessions at
      their own institutions. All of the residents (100%) would recommend this course
      to others. CONCLUSIONS: The ARC boot camp is an effective intervention for
      improving radiation oncology residents' knowledge and understanding of anatomy
      and radiology in addition to enhancing their confidence and accuracy in
      contouring.

PMID- 25596107
TI  - Brachytherapy improves biochemical failure-free survival in low- and intermediate
      risk prostate cancer compared with conventionally fractionated external beam
      radiation therapy: a propensity score matched analysis.
AB  - PURPOSE: To compare, in a retrospective study, biochemical failure-free survival
      (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate
      cancer patients who received brachytherapy (BT) (either low-dose-rate
      brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam
      radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT)
      alone. METHODS AND MATERIALS: Patient data were obtained from the ProCaRS
      database, which contains 7974 prostate cancer patients treated with primary
      radiation therapy at four Canadian cancer institutions from 1994 to 2010.
      Propensity score matching was used to obtain the following 3 matched cohorts with
      balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2)
      intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT
      versus EBRT. Kaplan-Meier survival analysis was performed to compare differences
      in bFFS (primary endpoint) and OS in the 3 matched groups. RESULTS: Propensity
      score matching created acceptable balance in the baseline prognostic factors in
      all matches. Final matches included 2 1:1 matches in the intermediate-risk
      cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total
      n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400).
      Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan
      Meier survival analysis showed that all BT treatment options were associated with
      statistically significant improvements in bFFS when compared with EBRT in all
      cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001;
      intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR
      2.90, P=.004). No significant difference in OS was found in all comparisons
      (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR
      BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500). CONCLUSIONS:
      Propensity score matched analysis showed that BT options led to statistically
      significant improvements in bFFS in low- and intermediate-risk prostate cancer
      patient populations.

PMID- 25596108
TI  - Gastrointestinal dose-histogram effects in the context of dose-volume-constrained
      prostate radiation therapy: analysis of data from the RADAR prostate radiation
      therapy trial.
AB  - PURPOSE: To use a high-quality multicenter trial dataset to determine dose-volume
      effects for gastrointestinal (GI) toxicity following radiation therapy for
      prostate carcinoma. Influential dose-volume histogram regions were to be
      determined as functions of dose, anatomical location, toxicity, and clinical
      endpoint. METHODS AND MATERIALS: Planning datasets for 754 participants in the
      TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT)
      Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a
      median of 72 months. A rank sum method was used to define dose-volume cut-points
      as near-continuous functions of dose to 3 GI anatomical regions, together with a
      comprehensive assessment of significance. Univariate and multivariate ordinal
      regression was used to assess the importance of cut-points at each dose. RESULTS:
      Dose ranges providing significant cut-points tended to be consistent with those
      showing significant univariate regression odds-ratios (representing the
      probability of a unitary increase in toxicity grade per percent relative volume).
      Ranges of significant cut-points for rectal bleeding validated previously
      published results. Separation of the lower GI anatomy into complete anorectum,
      rectum, and anal canal showed the impact of mid-low doses to the anal canal on
      urgency and tenesmus, completeness of evacuation and stool frequency, and mid
      high doses to the anorectum on bleeding and stool frequency. Derived multivariate
      models emphasized the importance of the high-dose region of the anorectum and
      rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency
      and tenesmus, and low-to-mid doses to the anal canal for stool frequency,
      diarrhea, evacuation, and bleeding. CONCLUSIONS: Results confirm anatomical
      dependence of specific GI toxicities. They provide an atlas summarizing dose
      histogram effects and derived constraints as functions of anatomical region,
      dose, toxicity, and endpoint for informing future radiation therapy planning.

PMID- 25596109
TI  - Optimizing 4-dimensional magnetic resonance imaging data sampling for respiratory
      motion analysis of pancreatic tumors.
AB  - PURPOSE: To determine the optimum sampling strategy for retrospective
      reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization
      of tumor and organs at risk for radiation therapy purposes. METHODS AND
      MATERIALS: For optimization, we compared 2 surrogate signals (external
      respiratory bellows and internal MRI navigators) and 2 MR sampling strategies
      (Cartesian and radial) in terms of image quality and robustness. Using the
      optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D
      motion. Region of interest analysis was performed to characterize the respiratory
      induced motion of the tumor and organs at risk simultaneously. RESULTS: The MRI
      navigator was found to be a more reliable surrogate for pancreatic motion than
      the respiratory bellows signal. Radial sampling is most benign for undersampling
      artifacts and intraview motion. Motion characterization revealed interorgan and
      interpatient variation, as well as heterogeneity within the tumor. CONCLUSIONS: A
      robust 4D-MRI method, based on clinically available protocols, is presented and
      successfully applied to characterize the abdominal motion in a small number of
      pancreatic cancer patients.

PMID- 25596111
TI  - Detection and automated scoring of dicentric chromosomes in nonstimulated
      lymphocyte prematurely condensed chromosomes after telomere and centromere
      staining.
AB  - PURPOSE: To combine telomere and centromere (TC) staining of premature chromosome
      condensation (PCC) fusions to identify dicentrics, centric rings, and acentric
      chromosomes, making possible the realization of a dose-response curve and
      automation of the process. METHODS AND MATERIALS: Blood samples from healthy
      donors were exposed to (60)Co irradiation at varying doses up to 8 Gy, followed
      by a repair period of 8 hours. Premature chromosome condensation fusions were
      carried out, and TC staining using peptide nucleic acid probes was performed.
      Chromosomal aberration (CA) scoring was carried out manually and automatically
      using PCC-TCScore software, developed in our laboratory. RESULTS: We successfully
      optimized the hybridization conditions and image capture parameters, to increase
      the sensitivity and effectiveness of CA scoring. Dicentrics, centric rings, and
      acentric chromosomes were rapidly and accurately detected, leading to a linear
      quadratic dose-response curve by manual scoring at up to 8 Gy. Using PCC-TCScore
      software for automatic scoring, we were able to detect 95% of dicentrics and
      centric rings. CONCLUSION: The introduction of TC staining to the PCC fusion
      technique has made possible the rapid scoring of unstable CAs, including
      dicentrics, with a level of accuracy and ease not previously possible. This new
      approach can be used for biological dosimetry in radiation emergency medicine,
      where the rapid and accurate detection of dicentrics is a high priority using
      automated scoring. Because there is no culture time, this new approach can also
      be used for the follow-up of patients treated by genotoxic therapy, creating the
      possibility to perform the estimation of induced chromosomal aberrations
      immediately after the blood draw.

PMID- 25596110
TI  - High nuclear hypoxia-inducible factor 1 alpha expression is a predictor of
      distant recurrence in patients with resected pancreatic adenocarcinoma.
AB  - PURPOSE: To evaluate nuclear hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression as a prognostic factor for distant recurrence (DR) and local
      recurrence (LR) after pancreatic adenocarcinoma resection. METHODS AND MATERIALS:
      Tissue specimens were collected from 98 patients with pancreatic adenocarcinoma
      who underwent resection without neoadjuvant therapy between January 2000 and
      December 2011. Local recurrence was defined as radiographic or pathologic
      evidence of progressive disease in the pancreas, pancreatic bed, or associated
      nodal regions. Distant recurrence was defined as radiographically or
      pathologically confirmed recurrent disease in other sites. Immunohistochemical
      staining was performed and scored by an independent pathologist blinded to
      patient outcomes. High HIF-1alpha overall expression score was defined as high
      percentage and intensity staining and thus score >1.33. Univariate analysis was
      performed for HIF-1alpha score with LR alone and with DR. Multivariate logistic
      regression was used to determine predictors of LR and DR. RESULTS: Median follow
      up time for all patients was 16.3 months. Eight patients (8%) demonstrated
      isolated LR, 26 patients (26.5%) had isolated DR, and 13 patients had both LR and
      DR. Fifty-three patients (54%) had high HIF-1alpha expression, and 45 patients
      (46%) had low HIF-1alpha expression. High HIF-1alpha expression was significantly
      associated with DR (P=.03), and low HIF-1alpha expression was significantly
      associated with isolated LR (P=.03). On multivariate logistic regression
      analysis, high HIF-1alpha was the only significant predictor of DR (odds ratio
      2.46 [95% confidence interval 1.06-5.72]; P=.03). In patients with a known
      recurrence, an HIF-1alpha score >=2.5 demonstrated a specificity of 100% for DR.
      CONCLUSIONS: High HIF-1alpha expression is a significant predictor of distant
      failure versus isolated local failure in patients undergoing resection of
      pancreatic adenocarcinoma. Expression of HIF-1alpha may have utility in
      determining candidates for adjuvant local radiation therapy and systemic
      chemotherapy.

PMID- 25596112
TI  - Categorized diagnoses and procedure records in an administrative database
      improved mortality prediction.
AB  - OBJECTIVES: Comorbidity measures are widely used in administrative databases to
      predict mortality. The Japanese Diagnosis Procedure Combination database is
      unique in that secondary diagnoses are recorded into subcategories, and
      procedures are precisely recorded. We investigated the influence of these
      features on the performance of mortality prediction models. STUDY DESIGN AND
      SETTING: We obtained data of adult patients with main diagnosis of acute
      myocardial infarction, congestive heart failure, acute cerebrovascular disease,
      gastrointestinal hemorrhage, pneumonia, or septicemia during a 1-year period.
      Multiple models were constructed representing different subcategories from which
      Charlson and Elixhauser comorbidities were extracted. Prevalence of comorbidities
      and C statistics of logistic regression models predicting in-hospital mortality
      was compared. Associations between four procedures (computed tomography, oxygen
      administration, urinary catheter, and vasopressors) and mortality were also
      evaluated. RESULTS: C statistics of the model using all secondary diagnoses
      (Charlson: 0.717; Elixhauser: 0.762) were greater than those using a limited
      subcategory to strictly specify comorbidities (Charlson: 0.708; Elixhauser:
      0.744). However, misidentification of complications and main diagnoses as
      comorbidities was observed in the all-diagnosis model. The four procedures were
      associated with mortality. CONCLUSION: Subcategorized diagnoses allowed correct
      identification of comorbidities and procedures predicted mortality. Incorporation
      of these two features should be considered for other administrative databases.

PMID- 25596113
TI  - Multilocus sequence typing of Candida albicans isolates from a burn intensive
      care unit in Iran.
AB  - Burn intensive care unit (BICU) patients are specifically exposed to deep-seated
      nosocomial infections due to Candida albicans. Superficial carriage of C.
      albicans is a potential source of infection and dissemination, and typing methods
      could be useful to trace the different isolates. Multilocus sequence typing is a
      powerful genotyping method for pathogenic micro-organisms, including Candida
      albicans. Thirty clinical isolates of C. albicans obtained from 22 patients that
      were admitted to the BICU from a burn hospital at Sari, Mazandaran state, Iran,
      were studied epidemiologically by multilocus sequence typing (MLST). Seventy-five
      variable nucleotide sites were found. Sixty-two alleles were identified among the
      seven loci of the C. albicans isolates and one new allele was obtained. Eighteen
      diploid sequence types (DSTs) were identified, and among those 10 were new. These
      isolates belonged to nine clonal clusters (CCs) while two isolates occurred as
      singletons. Eleven (36.7 %) isolates belonged to CC 124 after eBURST analysis and
      13 isolates (43.3 %) were assigned to clade 4. Approximately 17 % of the 30
      isolates belonged to clade 1 (CC 69 and CC 766). Isolates from several patients
      with burns were found to be related genetically. Some patients yielded multiple
      isolates with identical DSTs, suggesting colonization or infection caused by
      cross-contamination between patients. Isolates that show identical or similar
      allelic profiles are presumed to be identical or closely related and may be used
      to evaluate the genetic relationships between isolates from a specific
      environment such as the BICU. 

PMID- 25596114
TI  - Clinical significance of periodic detection of hepatitis B virus YVDD mutation by
      ultrasensitive real-time amplification refractory mutation system quantitative
      PCR during lamivudine treatment in patients with chronic hepatitis B.
AB  - Monitoring hepatitis B virus (HBV) mutants periodically during nucleoside
      analogue treatment is of great clinical significance, particularly in
      persistently HBV DNA-positive patients. However, few studies have investigated
      the dynamic changes of HBV YMDD (Tyr-Met-Asp-Asp) and YVDD (Tyr-Val-Asp-Asp)
      populations in chronic hepatitis B (CHB) patients whilst undergoing lamivudine
      (LMV) treatment. In this study, we sought to investigate the dynamic changes of
      HBV YMDD and YVDD variants by ultrasensitive real-time amplification refractory
      mutation system quantitative PCR (RT-ARMS-qPCR) and evaluate its significance for
      changes in the treatment of CHB patients. RT-ARMS-qPCR was established and
      evaluated with standard recombinant plasmids. Fifteen CHB patients receiving LMV
      (100 mg daily) were consecutively recruited and followed up for 60 weeks. Serum
      samples were obtained from each patient at baseline and every 12 weeks. The total
      HBV DNA, HBV YMDD DNA and YVDD DNA levels were measured using RT-ARMS-qPCR at all
      given time points after treatment. Routine liver biochemistry parameters,
      including aspartate aminotransferase and alanine aminotransferase, were also
      measured every 12 weeks. The linear range of the assay was between 1*10(12) and
      1*10(5) copies ml(-1). The low detection limit was 1*10(4) copies ml(-1). After
      60 weeks of LMV treatment, nine patients experienced virological breakthrough.
      The YVDD variant could be detected 12-48 weeks before virological breakthrough.
      The YVDD variant was detected as the predominant population (range 69.4-100 %) in
      patients by the time virological breakthrough appeared. We concluded that RT-ARMS
      qPCR was sensitive for the detection and quantification of low levels of HBV
      mutation. Periodic detection of HBV YM(V)DD every 12 weeks during LMV treatment
      is helpful for therapeutic decision making. 

PMID- 25596115
TI  - Molecular epidemiological survey of the quinolone- and carbapenem-resistant
      genotype and its association with the type III secretion system in Pseudomonas
      aeruginosa.
AB  - This study evaluated the predictors of mortality and the impact of inappropriate
      therapy on the outcomes of patients with bacteraemia and ventilator-associated
      pneumonia (VAP). Additionally, we evaluated the correlation of the type III
      secretion system (TTSS) effector genotype with resistance to carbapenems and
      fluoroquinolones, mutations in the quinolone resistance-determining regions
      (QRDRs), metallo-beta-lactamase and virulence factors. A retrospective cohort was
      conducted at a tertiary hospital in patients with multidrug-resistant (MDR) P.
      aeruginosa bacteraemia (157 patients) and VAP (60 patients). The genes for
      blaIMP, blaVIM, blaSIM, blaGIM and blaSPM and virulence genes (exoT, exoS, exoY,
      exoU, lasB, algD and toxA) were detected; sequencing was conducted for QRDR genes
      on fluoroquinolone-resistant strains. The multivariate analyses showed that the
      predictors independently associated with death in patients with bacteraemia were
      cancer and inappropriate therapy. Carbapenem resistance was more frequent among
      strains causing VAP (53.3 %), and in blood we observed the blaSPM genotype (66.6
      %) and blaVIM genotype (33.3 %). The exoS gene was found in all isolates, whilst
      the frequency was low for exoU (9.4 %). Substitution of threonine to isoleucine
      at position 83 in gyrA was the most frequent mutation among fluoroquinolone
      resistant strains. Our study showed a mutation at position 91 in the parC gene
      (Glu91Lys) associated with a mutation in gyrA (Thre83Ile) in a strain of
      extensively drug-resistant P. aeruginosa, with the exoT(+)exoS(+)exoU(+)
      genotype, that has not yet been described in Brazil to the best of our knowledge.
      This comprehensive analysis of resistance mechanisms to carbapenem and
      fluoroquinolones and their association with TTSS virulence genes, covering MDR P.
      aeruginosa in Brazil, is the largest reported to date. 

PMID- 25596116
TI  - Molecular identification and antifungal susceptibility of 186 Candida isolates
      from vulvovaginal candidiasis in southern China.
AB  - There is limited information regarding the molecular epidemiology and antifungal
      susceptibilities of Candida isolates using the Neo-Sensitabs method in patients
      with vulvovaginal candidiasis (VVC). From August 2012 to March 2013, 301 non
      pregnant patients aged 18-50 years with suspected VVC were prospectively screened
      at a teaching hospital in southern China. The vaginal isolates were identified by
      DNA sequencing of internal transcribed spacer and the D1/D2 domain. Antifungal
      susceptibility testing of seven antifungal agents was performed using the Neo
      Sensitabs tablet diffusion method. Candida species were isolated from 186 cases
      (61.79 %). The most common pathogen was Candida albicans (91.4 %), followed by
      Candida glabrata (4.3 %), Candida tropicalis (3.2 %) and Candida parapsilosis
      (1.1 %). The susceptibility rates to C. albicans were higher for caspofungin,
      voriconazole and fluconazole than those for itraconazole, miconazole,
      ketoconazole and terbinafine (P<0.01). The resistance rates to C. albicans were
      4.7, 6.5, 7.1, 7.6, 12.3, 27.7 and 74.7 % for caspofungin, miconazole,
      itraconazole, voriconazole, fluconazole, ketoconazole and terbinafine,
      respectively. No drugs tested apart from fluconazole exhibited differences in
      resistance between C. albicans and non-albicans Candida isolates. The results
      demonstrate that, using DNA sequencing, C. albicans is the most common isolate
      from Chinese patients with VVC. Caspofungin, voriconazole and fluconazole may be
      preferable to other azoles and terbinafine in the treatment of VVC. 

PMID- 25596117
TI  - Risk factors, outcomes and epidemiology associated with Clostridium difficile
      infection in patients with haematological malignancies in a tertiary care
      hospital in China.
AB  - The purpose of this study was to evaluate the risk factors, outcomes and
      epidemiology associated with Clostridium difficile infection (CDI) in patients
      with haematological malignancies in a tertiary care hospital in China. C.
      difficile screening was performed on patients admitted for chemotherapy or
      haematopoietic stem cell transplantation between 2009 and 2013. C. difficile
      isolates were analysed by multilocus sequence typing, and a retrospective chart
      review was performed on all patients with a positive toxin assay. CDI was
      diagnosed in 21 haematology-oncology ward patients and 14 marrow transplantation
      service patients for a cumulative incidence of 1.89/1000 and 3.69/1000 patient
      days, respectively. Univariate analyses showed that patients who received
      etoposide had an increased risk of CDI (odds ratio 4.25, 95 % confidence interval
      1.32-13.64). There was only one patient death, for which CDI was not the primary
      cause. Ten sequence types (STs) were identified, of which ST-3 and ST-54 were the
      most common; the hypervirulent ST-1 (ribotype 027) and ST-11 (ribotype 078) C.
      difficile strains were not detected in the patients in this study. The incidence
      of CDI did not differ between patients receiving chemotherapy and those receiving
      haematopoietic stem cell transplantation. The only risk factor for chemotherapy
      patients was treatment with etoposide. 

PMID- 25596118
TI  - Comparison of loop-mediated isothermal amplification and real-time PCR for
      detecting Bordetella pertussis.

PMID- 25596119
TI  - Investigation of the population structure of Mycobacterium abscessus complex
      strains using 17-locus variable number tandem repeat typing and the further
      distinction of Mycobacterium massiliense hsp65 genotypes.
AB  - Mycobacterium abscessus complex is a significant pathogen in patients with non
      cystic fibrosis (non-CF). Nevertheless, there is little description of the
      genetic diversity of this species. The aims of this study were to investigate the
      distribution of M. abscessus complex isolated from respiratory specimens by
      variable number tandem repeat (VNTR) typing. The results of 104 clinical isolates
      from 104 non-CF patients were compared using PFGE, hsp65 genotypes and
      clarithromycin susceptibility. The allelic diversity (Hunter-Gaston
      Discriminatory Index) of the 17 loci examined by VNTR typing was high (0.977). We
      determined that C28 sequevar erm(41) genotypes and clarithromycin-acquired
      resistance isolates were scattered in the minimum spanning tree. Intriguingly,
      VNTR typing and PFGE were highly congruent and revealed that there were clear
      examples of grouping of isolates from different individuals amongst both M.
      abscessus and M. massiliense, and showed five clusters of distinct identical
      isolates. Within these clusters, M. massiliense hsp65 type I formed three
      different clusters. Although the distribution of M. massiliense hsp65 type II-1
      was low (9.3 %), M. massiliense hsp65 type II-1 isolates separated from clusters
      contained hsp65 type I isolates. Thus, M. massiliense hsp65 genotypes could be
      discriminated by analysing VNTRs with sufficient genetic distance for intra
      species-level discrimination. 

PMID- 25596120
TI  - Evaluation of the Speed-Oligo Mycobacteria assay for the identification of
      nontuberculous mycobacteria.
AB  - Nontuberculous mycobacteria (NTM) causing human infectious disease have become
      increasingly common. Rapid and accurate identification to the species level is,
      therefore, critical. The Speed-Oligo Mycobacteria assay is an
      oligochromatographic method that was made available recently for the
      identification and differentiation of mycobacteria. The present study aimed to
      evaluate the performance of the Speed-Oligo Mycobacteria assay for the
      identification of NTM. We examined a total of 62 strains (9 type strains, 19
      reference strains and 34 clinical isolates) belonging to 13 different species
      (Mycobacterium intracellulare, M. fortuitum, M. gordonae, M. kansasii, M.
      marinum, M. peregrinum, M. scrofulaceum, M. abscessus, M. bovis BCG, M. chelonae,
      M. avium, M. malmoense and M. xenopi). The Speed-Oligo Mycobacteria assay was
      performed according to the manufacturer's instructions. Discrepant results
      between Speed-Oligo Mycobacteria and the original identification were reassessed
      by the Speed-Oligo Mycobacteria assay and resolved by the GenoType Mycobacterium
      CM assay and by sequencing of 16S rRNA and protein-encoding genes. We found 93.5
      % (58/62) concordance for the identification of NTM as compared with the original
      identification. Three strains were erroneously identified by Speed-Oligo
      Mycobacteria: one M. kansasii strain was identified as Mycobacterium tuberculosis
      complex, and one M. chelonae strain and one M. peregrinum strain were both
      identified as Mycobacterium abscessus. Moreover, one M. chelonae strain was not
      identified by Speed-Oligo Mycobacteria since it did not react with any species
      specific probe. For these strains, sequencing of the genes hsp65, 16S rRNA and
      rpoB and the GenoType Mycobacterium CM assay were performed. The Speed-Oligo
      Mycobacteria assay can be a useful tool for the rapid and easy identification of
      the most common NTM. If applied in clinical practice it could reduce diagnostic
      delays and contribute to correct clinical and better management of infections
      caused by NTM. 

PMID- 25596121
TI  - Burden of fungal disease in Ireland.
AB  - Our objective was to estimate the burden of fungal disease on the island of
      Ireland, as part of a coordinated project estimating the global burden. Published
      epidemiology data describing fungal infection in Ireland were identified.
      Population and underlying disease data were collected for 2010 and a structured
      set of assumptions were applied to estimate burden of fungal disease based on
      immunosuppression, chronic disease, and other demographic information indicating
      predisposition to fungal infection. From Ireland's population of 6.4 million, we
      estimate 117, 000 patients develop significant fungal disease each year. By far
      the most common fungal disease is recurrent Candida vaginitis, with an estimated
      95, 000 episodes annually (3000 per 100 000 women). Other fungal diseases which
      may be less well recognized are severe asthma with fungal sensitization and
      allergic bronchopulmonary aspergillosis, with estimated episodes per year of 11,
      700 and 9000, respectively (182 and 140 per 100, 000 population, respectively).
      The model also estimates 450 episodes of invasive aspergillosis, 200 of chronic
      pulmonary aspergillosis, 600 of oesophageal candidiasis and 450 of candidaemia
      per year (7, 3, 9 and 6 episodes per 100, 000 population, respectively). This is,
      we believe, the first attempt to estimate the burden of fungal disease in our
      population and provides a basis for estimating its impact on human health and
      resource use.

PMID- 25596122
TI  - Multiple-locus variable-number tandem repeat analysis and clinical
      characterization of Leptospira interrogans canine isolates.
AB  - Canine leptospirosis occurs worldwide; however, information on the relationship
      between Leptospira serotypes/genotypes and virulence in dogs remains limited. We
      investigated the molecular characteristics of Leptospira interrogans canine
      isolates belonging to three serogroups using multiple-locus variable-number
      tandem repeat analysis (MLVA) and the effects of each serotype/genotype on the
      clinical characteristics of leptospirosis in dogs. MLVA using 11 loci of the
      three major L. interrogans serogroups in Japan, Australis (32 strains from 21
      dogs), Autumnalis (12; 7) and Hebdomadis (66; 39), revealed more divergent
      genetic heterogeneity within each serogroup than multilocus sequence typing
      (MLST), and they formed two, three and five clusters (CLs), respectively. Lethal
      infections were caused by all Leptospira serogroup isolates (70.3 % with
      Hebdomadis, 83.3 % with Australis and 100 % with Autumnalis) or Leptospira
      isolates belonging to all the CLs (57.1-100 %) without any significant
      differences. A significant difference in hyperaemia and haemorrhage of mucus
      membrane was observed between serogroups Australis and Autumnalis (P = 0.03).
      Leptospira isolates of Australis CL2 caused no hyperaemia and haemorrhage from
      mucus membrane, whereas those of Australis CL1, Autumnalis CL3 and Hebdomadis CL1
      and CL3 did (P<0.05). Significant differences in creatinine (Cre) levels were
      observed between serogroups Australis and Hebdomadis (P = 0.02). In addition,
      significant differences in blood urea nitrogen levels were observed between
      serogroups Australis and Hebdomadis (P = 0.004) and Australis and Autumnalis (P =
      0.02). Based on MLVA types, a significant difference in Cre levels was observed
      between Hebdomadis CL1 and CL4 (P = 0.0018). Our results indicated that MLVA had
      a higher discriminatory power and was more concordant with serotyping than MLST.
      Although all Leptospira serotypes and genotypes caused lethal infections in dogs,
      the L. interrogans serogroup Australis strains were more likely to cause severe
      kidney damage than Autumnalis and Hebdomadis, which may be more critical to the
      outcome of infected dogs than haemorrhage. Our results also suggest that the
      virulence mechanisms and target organs in dogs may differ by Leptospira genotype.

PMID- 25596123
TI  - Is polyhexamethylene-guanidine hydrochloride (PHMGH) sporicidal? A critical
      review.

PMID- 25596124
TI  - In vitro activity of miltefosine in combination with voriconazole or amphotericin
      B against clinical isolates of Scedosporium spp.

PMID- 25596125
TI  - Microbiological characteristics of acute osteoarticular infections in children.
AB  - This study aimed to describe the microbiological characteristics of acute septic
      arthritis (SA) and osteomyelitis (OM) in children. Cases of children (0-15 years)
      with SA/OM were identified through a retrospective search of hospital discharge
      codes over a six-year period. In addition, a systematic literature search and
      meta-analysis of studies reporting culture results of children with SA/OM was
      performed. In our retrospective chart review, we identified 65 cases of OM and 46
      cases of SA. The most frequently cultured organisms in both conditions were Gram
      positive cocci, primarily Staphylococcus aureus. On admission, most patients had
      a normal white blood cell count (WCC) but elevated C-reactive protein (CRP)
      and/or erythrocyte sedimentation rate (ESR). Bacteraemia was associated with a
      longer mean length of hospitalization for both infections. Considering our
      results and the meta-analysis, we found low rates of culture-positivity in cases
      of clinically confirmed infection. In SA, articular fluid was culture-positive in
      42.49% [95% confidence interval (CI) 28.39-57.23]. In OM, intra-operative samples
      were culture-positive in 52.65% (95% CI 30.54-74.22). Bacteraemia was detected in
      23.91% (95% CI 8.40-44.24) of children with SA and 21.48% (95% CI 10.89-34.47)
      with OM. Despite appropriate sampling, a positive microbiological diagnosis is
      often lacking in paediatric acute osteoarticular infection using standard culture
      based methods. This highlights the need for validation and use of more sensitive
      diagnostic methods, such as PCR.

PMID- 25596126
TI  - Aetiology of acute paediatric gastroenteritis in Bulgaria during summer months:
      prevalence of viral infections.
AB  - Paediatric acute gastroenteritis is a global public health problem. Comprehensive
      laboratory investigation for viral, bacterial and parasitic agents is helpful for
      improving management of acute gastroenteritis in health care settings and for
      monitoring and controlling the spread of these infections. Our study aimed to
      investigate the role of various pathogens in infantile diarrhoea in Bulgaria
      outside the classical winter epidemics of rotavirus and norovirus. Stool samples
      from 115 hospitalized children aged 0-3 years collected during summer months were
      tested for presence of 14 infectious agents - group A rotavirus, astrovirus,
      Giardia, Cryptosporidium and Entamoeba using ELISAs; norovirus by real-time RT
      PCR; picobirnavirus and sapovirus by RT-PCR; adenovirus using PCR, and
      Salmonella, Shigella, Escherichia coli, Yersinia and Campylobacter using standard
      bacterial cultures. Infectious origin was established in a total of 92 cases and
      23 samples remained negative. A single pathogen was found in 67 stools, of which
      rotaviruses were the most prevalent (56.7 %), followed by noroviruses (19.4 %),
      enteric adenoviruses (7.5 %), astroviruses (6.0 %), bacteria and parasites (4.5 %
      each) and sapoviruses (1.4 %). Rotavirus predominant genotypes were G4P[8] (46.3
      %) and G2P[4] (21.4 %); for astroviruses, type 1a was the most common, while the
      GII.4/2006b variant was the most prevalent among noroviruses. Bacteria were
      observed in five cases, with Salmonella sp. as the most prevalent, while
      parasites were found in ten stool samples, with Giardia intestinalis in five
      cases. The results demonstrated high morbidity associated with viral infections
      and that rotavirus and norovirus remain the most common pathogens associated with
      severe gastroenteritis during summer months in Bulgaria, a country with a
      temperate climate, and significant molecular diversity among circulating virus
      strains. 

PMID- 25596127
TI  - AtTGA4, a bZIP transcription factor, confers drought resistance by enhancing
      nitrate transport and assimilation in Arabidopsis thaliana.
AB  - To cope with environmental stress caused by global climate change and excessive
      nitrogen application, it is important to improve water and nitrogen use
      efficiencies in crop plants. It has been reported that higher nitrogen uptake
      could alleviate the damaging impact of drought stress. However, there is scant
      evidence to explain how nitrogen uptake affects drought resistance. In this study
      we observed that bZIP transcription factor AtTGA4 (TGACG motif-binding factor 4)
      was induced by both drought and low nitrogen stresses, and that overexpression of
      AtTGA4 simultaneously improved drought resistance and reduced nitrogen starvation
      in Arabidopsis. Following drought stress there were higher nitrogen and proline
      contents in transgenic AtTGA4 plants than in wild type controls, and activity of
      the key enzyme nitrite reductase (NIR) involved in nitrate assimilation processes
      was also higher. Expressions of the high-affinity nitrate transporter genes
      NRT2.1 and NRT2.2 and nitrate reductase genes NIA1 and NIA2 in transgenic plants
      were all higher than in wild type indicating that higher levels of nitrate
      transport and assimilation activity contributed to enhanced drought resistance of
      AtTGA4 transgenic plants. Thus genetic transformation with AtTGA4 may provide a
      new approach to simultaneously improve crop tolerance to drought and low nitrogen
      stresses. 

PMID- 25596130
TI  - Telomere length differences between subcutaneous and visceral adipose tissue in
      humans.
AB  - Adipocyte hypertrophy and hyperplasia have been shown to be associated with
      shorter telomere length, which may reflect aging, altered cell proliferation and
      adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat
      distribution and AT cellular composition may contribute to obesity related
      metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are
      different between: (1) abdominal subcutaneous and omental fat depots, (2)
      superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and
      cells of the stromal vascular fraction (SVF). We further asked whether AT TL is
      related to age, anthropometric and metabolic traits. TL was analyzed by
      quantitative PCR in total human genomic DNA isolated from paired subcutaneous and
      visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in
      isolated small and large adipocytes and SVF cells. We find significantly shorter
      TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men
      and subgroups of lean and obese, and individuals with or without type 2 diabetes
      (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to
      visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = -0.205,
      P < 0.05) and independently of age with HbA1c (r = -0.5, P < 0.05). We found
      significant TL differences between superficial SAT of lean and obese as well as
      between individuals with our without T2D, but not between the two layers of SAT.
      Our data indicate that fat depot differences in TL mainly reflect shorter TL of
      SVF cells. In addition, we found an age and BMI-independent relationship between
      shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the
      regenerative capacity of AT more strongly than obesity alone.

PMID- 25596129
TI  - Oncogenic TPM3-ALK activation requires dimerization through the coiled-coil
      structure of TPM3.
AB  - Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can arise
      from anywhere in the body. Anaplastic lymphoma kinase (ALK) gene rearrangements,
      most often resulting in the tropomyosin 3 (TPM3)-ALK fusion gene, are the main
      causes of IMT. However, the mechanism of malignant transformation in IMT has yet
      to be elucidated. The purpose of this study was to clarify the role of the TPM3
      region in the transformation of IMT via TPM3-ALK. Lentivirus vectors containing a
      TPM3-ALK fusion gene lacking various lengths of TPM3 were constructed and
      expressed in HEK293T and NIH3T3 cell lines. Focus formation assay revealed loss
      of contact inhibition in NIH3T3 cells transfected with full-length TPM3-ALK, but
      not with ALK alone. Blue-native polyacrylamide gel electrophoresis (BN-PAGE)
      revealed that TPM3-ALK dimerization increased in proportion to the length of
      TPM3. Western blot showed phosphorylation of ALK, ERK1/2, and STAT3 in HEK293T
      cells transfected with TPM3-ALK. Thus, the coiled-coil structure of TPM3
      contributes to the transforming ability of the TPM3-ALK fusion protein, and
      longer TPM3 region leads to higher dimer formation. 

PMID- 25596131
TI  - Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through
      TLR2 signaling.
AB  - Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit
      potent immunosuppressive activity. They are increased in tumor-bearing hosts and
      contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate
      the tumor-supporting properties of MDSCs through pattern-recognition. Pam2
      lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor
      function by dendritic cell (DC)-priming that leads to NK cell activation and
      cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell
      progression/invasion by activating tumor-infiltrating macrophages. How MDSCs
      respond to TLR2 agonists has not yet been determined. In this study, we found
      intravenous administration of Pam2CSK4 systemically up-regulated the frequency of
      MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was
      accordingly increased in response to Pam2CSK4. MDSCs were not increased by
      Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using
      CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor
      bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC
      population sustained immune-suppressive properties, our study suggests that
      Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress
      antitumor immune response in tumor microenvironment. 

PMID- 25596128
TI  - CD36 is indispensable for thermogenesis under conditions of fasting and cold
      stress.
AB  - Hypothermia can occur during fasting when thermoregulatory mechanisms, involving
      fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane
      protein which facilitates membrane transport of long-chain FA in the FA consuming
      heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of
      triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold
      environment. In mice deficient for CD36 (CD36(-/-) mice), FA uptake is markedly
      reduced with a compensatory increase in glucose uptake in the heart and SkM,
      resulting in lower levels of blood glucose especially during fasting. However,
      the role of CD36 in thermogenic activity during fasting remains to be determined.
      In fasted CD36(-/-) mice, body temperature drastically decreased shortly after
      cold exposure. The hypothermia was accompanied by a marked reduction in blood
      glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic
      SkM. Biodistribution analysis using the FA analogue (125)I-BMIPP and the glucose
      analogue (18)F-FDG revealed that uptake of FA and glucose was severely impaired
      in BAT and glycolytic SkM in cold-exposed CD36(-/-) mice. Further, induction of
      the genes of thermogenesis in BAT was blunted in fasted CD36(-/-) mice after cold
      exposure. These findings strongly suggest that CD36(-/-) mice exhibit pronounced
      hypothermia after fasting due to depletion of energy storage in BAT and
      glycolytic SkM and to reduced supply of energy substrates to these tissues. Our
      study underscores the importance of CD36 for nutrient homeostasis to survive
      potentially life-threatening challenges, such as cold and starvation. 

PMID- 25596132
TI  - [Remote dermatological advice: a survey in three French regions].
AB  - BACKGROUND: General practitioners and specialists often seek advice from
      dermatologists based on digital pictures. This time-consuming activity is
      currently not valued nor well-established. We therefore conducted a survey to
      assess the extent and nature of such requests. PATIENTS AND METHODS: A
      questionnaire was sent to dermatologists working either at university hospitals
      or in private practice in three regions of France (Loire Atlantique, Rhone Alpes
      and Normandy). For two months, the dermatologists completed the same
      questionnaire for each specialized request. The following items were recorded:
      status of the dermatologist asked to provide a specialized opinion, region in
      which the request was made, status of the requesting practitioner, mode of
      request, type of disease, question asked, time taken to answer the request and
      result of the specialized advice. RESULTS: Thirty dermatologists, including 11 in
      private practice, participated in this study. We identified 287 requests. The
      majority of these requests came from general practitioners (30%) and
      dermatologists working in private practice (29%). These requests were sent by e
      mail using a non-secure professional e-mail address in 49% of cases or via
      smartphone in 29% of cases. The purpose of the requests was either
      diagnostic/therapeutic (36%) or solely therapeutic (39%). Relevant requests
      concerned dermatological manifestations in paediatric or cancer patients (23% and
      21% respectively), general dermatological diseases (21%) and wound management
      (14%). Nearly half of the specialized advice was provided in under 5minutes, and
      in 60% of cases a consultation with a dermatologist was avoided. CONCLUSION:
      Despite the small number of physicians taking part in the study, this non
      exhaustive survey confirms the usefulness of remote dermatological reviews and
      consultations, and identifies the main intervening physicians involved in this
      type of procedure. The study also raises potential medico-legal issues regarding
      the lack of data security covering medical information. There is thus a need for
      dermatologists to organize their activity in order to respond to such requests
      without exposing themselves to medico-legal consequences.

PMID- 25596133
TI  - Biodegradable nanoparticles designed for drug delivery: The number of
      nanoparticles impacts on cytotoxicity.
AB  - Nanostructured drug delivery systems are based on biocompatible and biodegradable
      components. Composition, size and membrane surface properties are characteristics
      that may influence cell viability in cytotoxicity assays. In this work, four
      nanostructured systems commonly used for drug delivery were prepared and
      cytotoxicity was evaluated on human lymphocytes and Balb/c 3T3 fibroblasts. The
      hemolytic potential was also investigated. Polymeric nanocapsules (NC) and
      nanospheres (NS), nanostructured lipid carriers (NLC) and liposomes were prepared
      and characterized for size, distribution, zeta potential and number per volume of
      the colloidal dispersion. Cell viability was evaluated, 24 and 48h, by MTT and
      neutral red assays (NR). Cells were incubated with each particle in eight
      different dilutions varying from 2.1*10(4) to 2.1*10(11)particles/mL. Diameter of
      nanoparticles was between 130 and 200nm, all samples exhibited narrow size
      distribution (polydispersity index below 0.1) and zeta potential varied from -6.8
      to -19.5mV. NC, NS and NLC reduced cell viability in a dilution dependent manner.
      For these nanoparticles, the higher number of particles induced cell death for
      both cell types. Liposomes did not cause loss of cell viability even at the
      highest number of particles. Results suggest that, depending on the kind of
      nanoparticle, the number of particles in the dispersion can negatively influence
      cell viability in pre-clinical drug development. 

PMID- 25596134
TI  - Transcriptomics hit the target: Monitoring of ligand-activated and stress
      response pathways for chemical testing.
AB  - High content omic methods provide a deep insight into cellular events occurring
      upon chemical exposure of a cell population or tissue. However, this improvement
      in analytic precision is not yet matched by a thorough understanding of molecular
      mechanisms that would allow an optimal interpretation of these biological
      changes. For transcriptomics (TCX), one type of molecular effects that can be
      assessed already is the modulation of the transcriptional activity of a
      transcription factor (TF). As more ChIP-seq datasets reporting genes specifically
      bound by a TF become publicly available for mining, the generation of target gene
      lists of TFs of toxicological relevance becomes possible, based on actual protein
      DNA interaction and modulation of gene expression. In this study, we generated
      target gene signatures for Nrf2, ATF4, XBP1, p53, HIF1a, AhR and PPAR gamma and
      tracked TF modulation in a large collection of in vitro TCX datasets from renal
      and hepatic cell models exposed to clinical nephro- and hepato-toxins. The result
      is a global monitoring of TF modulation with great promise as a mechanistically
      based tool for chemical hazard identification. 

PMID- 25596135
TI  - In vitro study of the neuropathic potential of the organophosphorus compounds
      trichlorfon and acephate.
AB  - Organophosphorus-induced delayed neuropathy (OPIDN) is a central and peripheral
      distal axonopathy characterized by ataxia and paralysis. Trichlorfon and acephate
      are two organophosphorus compounds (OPs) used worldwide as insecticide and which
      cause serious effects to non-target species. Despite that, the neuropathic
      potential of these OPs remains unclear. The present study addressed the
      neurotoxic effects and the neuropathic potential of trichlorfon and acephate in
      SH-SY5Y human neuroblastoma cells, by evaluating inhibition and aging of
      neuropathy target esterase (NTE), inhibition of acetylcholinesterase (AChE),
      neurite outgrowth, cytotoxicity and intracellular calcium. Additionally, the
      effects observed were compared to those of two well-studied OPs: mipafox (known
      as neuropathic) and paraoxon (known as non-neuropathic). Trichlorfon and mipafox
      presented the lowest percentage of reactivation of inhibited NTE and the lowest
      ratio IC50 NTE/IC50 AChE. Moreover, they caused inhibition and aging of at least
      70% of the activity of NTE at sub-lethal concentrations. All these effects have
      been associated with induction of OPIDN. When assayed at these concentrations,
      trichlorfon and mipafox reduced neurite outgrowth and increased intracellular
      calcium, events implicated in the development of OPIDN. Acephate caused effects
      similar to those caused by paraoxon (non-neuropathic OP) and was only able to
      inhibit 70% of NTE activity at lethal concentrations. These findings suggest that
      trichlorfon is potentially neuropathic, whereas acephate is not. 

PMID- 25596136
TI  - One-year outcomes of inhaled controller therapies added to systemic
      corticosteroids after asthma-related hospital discharge.
AB  - BACKGROUND: Much of the evidence on the early use of inhaled controllers after
      severe asthma exacerbations is about their short-term benefit, leaving a gap in
      evidence on their longer-term outcomes. METHODS: We used administrative health
      data from British Columbia, Canada (2001-2012) to evaluate readmission rate
      (primary outcome), adherence to controller medications, and use of reliever
      medications associated with different inhaled controller treatments as an add-on
      to systemic corticosteroids (SCS) over one-year following discharge from an
      asthma-related admission in individuals 12-55 years of age. Exposure was assessed
      in the 60 days after discharge, and categorized as monotherapy with SCS (SCS
      only) versus SCS plus inhaled controller therapy (SCS + inhaler); the latter was
      further divided into SCS + inhaled corticosteroid (SCS + ICS) and SCS + ICS and
      long-acting beta agonists (SCS + ICS/LABA). Propensity score-adjusted regression
      models were used to estimate relative rates (RR) of outcomes across exposure
      groups. RESULTS: The final cohort included 2,272 post-discharge periods (43.0%
      SCS-only, 26.9% SCS + ICS, and 30.1% SCS + ICS/LABA). Readmission rate was
      significantly lower in the SCS + inhaler versus SCS-only (RR = 0.74 [95%CI 0.59
      0.93]), but similar between SCS + ICS and SCS + ICS/LABA (RR = 0.78 [95%CI 0.59
      1.04]). Long-term adherence, defined as medication possession ratio, to
      controller medications was 83% higher in SCS + inhaler than SCS-only, and 64%
      higher in SCS + ICS/LABA than in SCS + ICS. The use of reliever medications was
      similar across exposure groups. CONCLUSION: Early initiation of inhaled
      controllers after discharge from an asthma-related hospitalization was associated
      with significantly better long-term adherence to controller medications as well
      as reduced rate of readmissions. Combination therapy with ICS/LABA seems to be at
      least as effective as mono-therapy with ICS in reducing the risk of readmission,
      with the added benefit of better long-term adherence.

PMID- 25596137
TI  - Elevated plasma alpha-defensins in patients with acute exacerbation of fibrotic
      interstitial pneumonia.
AB  - BACKGROUND: Patients with fibrosing interstitial lung diseases can develop acute
      exacerbation (AE). The aetiology of AE remains obscure, but neutrophils might
      play a pivotal role in the pathogenesis. Neutrophils store azurophil granules
      containing defensins that are antimicrobial peptides that also function in
      regulating the inflammatory response. The present study evaluates plasma levels
      of defensins in patients with AE of interstitial pneumonia (AE-IP) to determine
      their role(s) in the pathogenesis of AE-IP and whether defensins could serve as a
      biomarker of AE-IP. METHODS: Plasma levels of defensins including human
      neutrophil peptides (HNPs) and human beta defensin 2 (HBD2) were measured using
      ELISA in 21 patients with AE-IP, 44 with stable (S)-IP, nine with IP complicated
      with pulmonary infection (Infec-IP), and in 23 healthy volunteers. Lung HNP
      expression was immunohistochemically analyzed in biopsy and autopsy tissues
      diagnosed as S-IP and AE-IP. RESULTS: Plasma levels of HNPs were significantly
      higher in patients with AE-IP than with S-IP, but did not differ from those with
      Infec-IP and were not associated with other clinical features and prognosis.
      Plasma HNP were not specific in terms of distinguishing AE-IP from S-IP.
      Immunohistochemical analysis showed increased HNPs expression in accumulated
      neutrophils from patients with AE-IP. Plasma levels of HBD2 did not differ among
      patients with AE-IP, S-IP and Infec-IP. CONCLUSIONS: Elevated plasma levels of
      HNPs were higher in AE-IP than in S-IP, but not specific enough to serve as
      candidate biomarkers of AE-IP. Further studies are needed to clarify the role of
      defensins in the pathogenesis of AE-IP.

PMID- 25596138
TI  - Therapeutic equivalence of budesonide/formoterol delivered via breath-actuated
      inhaler vs pMDI.
AB  - RATIONALE: To assess equivalence of twice daily (bid) budesonide/formoterol
      (BUD/FM) 160/4.5 MUg via breath-actuated metered-dose inhaler (BAI) versus
      pressurized metered-dose inhaler (pMDI). METHODS: This 12-week, double-blind,
      multicenter, parallel-group study, randomized adolescents and adults (aged >=12
      years) with asthma (and >=3 months daily use of inhaled corticosteroids) to
      BUD/FM BAI 2 * 160/4.5 MUg bid, BUD/FM pMDI 2 * 160/4.5 MUg bid, or BUD pMDI 2 *
      160 MUg bid. Inclusion required prebronchodilator forced expiratory volume in one
      second (FEV1) >=45 to <=85% predicted, and reversibility of >=12% in FEV1 (ages
      12 to <18 years) or >=12% and 200 mL (ages >=18 years). Confirmation that 60-min
      postdose FEV1 response to BUD/FM pMDI was superior to BUD pMDI was required
      before equivalence testing. Therapeutic equivalence was shown by treatment effect
      ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV1 and predose FEV1
      within confidence intervals (CIs) of 80-125%. RESULTS: Mean age of 214 randomized
      patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose
      FEV1 treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment
      effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV1 (1.01; 95% CI,
      0.97-1.05) and predose FEV1 (1.03; 95% CI, 0.99-1.08) were within predetermined
      CIs for therapeutic equivalence. Adverse event profiles, tolerability, and
      patient-reported ease of use were similar. CONCLUSIONS: BUD/FM 2 * 160/4.5 MUg
      bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The
      introduction of BUD/FM BAI would expand options for delivering inhaled
      corticosteroid/long-acting beta2-agonist combination therapy to patients with
      moderate-to-severe asthma. ClinicalTrials.gov NCT01360021.

PMID- 25596140
TI  - Clinical implications of intracoronary imaging in cardiac allograft vasculopathy.

PMID- 25596139
TI  - Comparison of coronary artery calcium presence, carotid plaque presence, and
      carotid intima-media thickness for cardiovascular disease prediction in the Multi
      Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Presence of coronary artery calcium (CAC), carotid plaque, and
      increased carotid intima-media thickness (IMT) may indicate elevated
      cardiovascular disease (CVD) risk; however, no large studies have compared them
      directly. This study compares predictive uses of CAC presence, carotid artery
      plaque presence, and high IMT for incident CVD events. METHODS AND RESULTS:
      Participants were from the Multi-Ethnic Study of Atherosclerosis (MESA).
      Predictive values of carotid plaque, IMT, and CAC presence were compared using
      Cox proportional hazards models, c-statistics, and net reclassification indices.
      The 6779 participants were mean (SD) 62.2 (10.2) years old; 49.9% had CAC, and
      46.7% had carotid plaque. The mean left and right IMT were 0.754 (0.210) mm and
      0.751 (0.187) mm, respectively. After 9.5 years (mean), 538 CVD events, 388
      coronary heart disease (CHD) events, and 196 stroke/transient ischemic attacks
      were observed. CAC presence was a stronger predictor of incident CVD and CHD than
      carotid ultrasound measures. Mean IMT>=75th percentile (for age, sex, and race)
      alone did not predict events. Compared with traditional risk factors, c
      statistics for CVD (c=0.756) and CHD (c=0.752) increased the most by the addition
      of CAC presence (CVD, 0.776; CHD, 0.784; P<0.001) followed by carotid plaque
      presence (CVD, c=0.760; CHD, c=0.757; P<0.05). Compared with risk factors
      (c=0.782), carotid plaque presence (c=0.787; P=0.045) but not CAC (c=0.785;
      P=0.438) improved prediction of stroke/transient ischemic attacks. CONCLUSIONS:
      In adults without CVD, CAC presence improves prediction of CVD and CHD more than
      carotid plaque presence or high IMT. CAC and carotid ultrasound parameters
      performed similarly for stroke/transient ischemic attack event prediction.

PMID- 25596141
TI  - Fractionating E-wave deceleration time into its stiffness and relaxation
      components distinguishes pseudonormal from normal filling.
AB  - BACKGROUND: Pseudonormal Doppler E-wave filling patterns indicate diastolic
      dysfunction but are indistinguishable from the normal filling pattern. For
      accurate classification, maneuvers to alter load or to additionally measure peak
      E' are required. E-wave deceleration time (DT) has been fractionated into its
      stiffness (DTs) and relaxation (DTr) components (DT=DTs+DTr) by analyzing E-waves
      via the parametrized diastolic filling formalism. The method has been validated
      with DTs and DTr correlating with simultaneous catheterization-derived stiffness
      (dP/dV) and relaxation (tau) with r=0.82 and r=0.94, respectively. We hypothesize
      that DT fractionation can (1) distinguish between unblinded (E' known) normal
      versus pseudonormal age-matched groups with normal left ventricular ejection
      fraction, and (2) distinguish between blinded (E' unknown) normal versus
      pseudonormal groups, based solely on E-wave analysis. METHODS AND RESULTS: Data
      (763 E-waves) from 15 age-matched, pseudonormal (elevated E/E') and 15 normal
      subjects were analyzed. Conventional echocardiographic and parametrized diastolic
      filling stiffness (k) and relaxation (c) parameters and DTs and DTr were
      compared. Conventional diastolic function parameters did not differentiate
      between unblinded groups, whereas k, c (P<0.001) and DTs, DTr (P<0.001) did.
      Independent, blinded (E' not provided) analysis of 42 subjects (30 subjects from
      unblinded training set and 12 additional subjects from validation set, 581 E
      waves) showed that R (=DTr/DT) had high sensitivity (0.90) and specificity (0.86)
      in differentiating pseudonormal from normal once E' revealed actual
      classification. CONCLUSIONS: arametrized diastolic filling-based E-wave analysis
      (k, c or DTs and DTr) can differentiate normal versus pseudonormal filling
      patterns without requiring knowledge of E'.

PMID- 25596142
TI  - Relative flow reserve derived from quantitative perfusion imaging may not
      outperform stress myocardial blood flow for identification of hemodynamically
      significant coronary artery disease.
AB  - BACKGROUND: Quantitative myocardial perfusion imaging is increasingly used for
      the diagnosis of coronary artery disease. Quantitative perfusion imaging allows
      to noninvasively calculate fractional flow reserve (FFR). This so-called relative
      flow reserve (RFR) is defined as the ratio of hyperemic myocardial blood flow
      (MBF) in a stenotic area to hyperemic MBF in a normal perfused area. The aim of
      this study was to assess the value of RFR in the detection of significant
      coronary artery disease. METHODS AND RESULTS: From a clinical population of
      patients with suspected coronary artery disease who underwent oxygen-15-labeled
      water cardiac positron emission tomography and invasive coronary angiography, 92
      patients with single- or 2-vessel disease were included. Intermediate lesions
      (diameter stenosis, 30%-90%; n=75) were interrogated by FFR. Thirty-eight (41%)
      vessels were deemed hemodynamically significant (>90% stenosis or FFR<=0.80).
      Hyperemic MBF, coronary flow reserve, and RFR were lower for vessels with a
      hemodynamically significant lesion (2.01+/-0.78 versus 2.90+/-1.16 mL.min(-1).g(
      1); P<0.001, 2.27+/-1.03 versus 3.10+/-1.29; P<0.001, and 0.67+/-0.23 versus
      0.93+/-0.15; P<0.001, respectively). The correlation between RFR and FFR was
      moderate (r=0.54; P<0.01). Receiver operator characteristic curve analysis showed
      an area under the curve of 0.82 for RFR, which was not significantly higher
      compared with that for hyperemic MBF and coronary flow reserve (0.76; P=0.32 and
      0.72; P=0.08, respectively). CONCLUSIONS: Noninvasive estimation of FFR by
      quantitative perfusion positron emission tomography by calculating RFR is
      feasible, yet only a trend toward a slight improvement of diagnostic accuracy
      compared with hyperemic MBF assessment was determined.

PMID- 25596143
TI  - Diagnostic accuracy of stress myocardial perfusion imaging compared to invasive
      coronary angiography with fractional flow reserve meta-analysis.
AB  - BACKGROUND: Hemodynamically significant coronary artery disease is an important
      indication for revascularization. Stress myocardial perfusion imaging is a
      noninvasive alternative to invasive fractional flow reserve for evaluating
      hemodynamically significant coronary artery disease. The aim was to determine the
      diagnostic accuracy of myocardial perfusion imaging by single-photon emission
      computed tomography, echocardiography, MRI, positron emission tomography, and
      computed tomography compared with invasive coronary angiography with fractional
      flow reserve for the diagnosis of hemodynamically significant coronary artery
      disease. METHODS AND RESULTS: The meta-analysis adhered to the Preferred
      Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed,
      EMBASE, and Web of Science were searched until May 2014. Thirty-seven studies,
      reporting on 4721 vessels and 2048 patients, were included. Meta-analysis yielded
      pooled sensitivity, pooled specificity, pooled likelihood ratios (LR), pooled
      diagnostic odds ratio, and summary area under the receiver operating
      characteristic curve. The negative LR (NLR) was chosen as the primary outcome. At
      the vessel level, MRI (pooled NLR, 0.16; 95% confidence interval [CI], 0.13-0.21)
      was performed similar to computed tomography (pooled NLR, 0.22; 95% CI, 0.12
      0.39) and positron emission tomography (pooled NLR, 0.15; 95% CI, 0.05-0.44), and
      better than single-photon emission computed tomography (pooled NLR, 0.47; 95% CI,
      0.37-0.59). At the patient level, MRI (pooled NLR, 0.14; 95% CI, 0.10-0.18)
      performed similar to computed tomography (pooled NLR, 0.12; 95% CI, 0.04-0.33)
      and positron emission tomography (pooled NLR, 0.14; 95% CI, 0.02-0.87), and
      better than single-photon emission computed tomography (pooled NLR, 0.39; 95% CI,
      0.27-0.55) and echocardiography (pooled NLR, 0.42; 95% CI, 0.30-0.59).
      CONCLUSIONS: Stress myocardial perfusion imaging with MRI, computed tomography,
      or positron emission tomography can accurately rule out hemodynamically
      significant coronary artery disease and can act as a gatekeeper for invasive
      revascularization. Single-photon emission computed tomography and
      echocardiography are less suited for this purpose.

PMID- 25596144
TI  - Physiologic stenosis severity, binary thinking, revascularization, and "hidden
      reality".

PMID- 25596145
TI  - Characterization of two thymosins as immune-related genes in common carp
      (Cyprinus carpio L.).
AB  - Prothymosin alpha (ProTalpha) and thymosin beta (Tbeta) belong to thymosin
      family, which consists of a series of highly conserved peptides involved in
      stimulating immune responses. ProTalpha b and Tbeta are still poorly studied in
      teleost. Here, the full-length cDNAs of ProTalpha b and Tbeta-like (Tbeta-l) were
      cloned and identified in common carp (Cyprinus carpio L.). The expressions of
      carp ProTalpha b and Tbeta-l exhibited rise-fall pattern and then trended to be
      stable during early development. After spring viraemia of carp virus (SVCV)
      infection, the carp ProTalpha b and Tbeta-l transcripts were significantly up
      regulated in some immune-related organs. When transiently over-expressed carp
      ProTalpha b and Tbeta-l in zebrafish, these two proteins up-regulated the
      expressions of T lymphocytes-related genes (Rag 1, TCR-gamma, CD4 and CD8alpha).
      These results suggest that carp ProTalpha b and Tbeta may ultimately enhance the
      immune response during viral infection and modulate the development of T
      lymphocytes in teleost. 

PMID- 25596146
TI  - Characterization of the duplicate L-SIGN and DC-SIGN genes in miiuy croaker and
      evolutionary analysis of L-SIGN in fishes.
AB  - Dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN/CD209) and
      liver/lymph node-specific ICAM-grabbing non-integrin (L-SIGN/CD299) which are
      homologues of DC-SIGN are important members in C-type lectin receptors family as
      key molecules to recognize and eliminate pathogens in the innate immune system.
      DC-SIGN and L-SIGN have become hot topics in recent studies which both served as
      cell adhesion and phagocytic pathogen recognition receptors in mammals. However,
      there have been almost no studies of DC-SIGN and L-SIGN structure and characters
      in fish, only DC-SIGN in the zebrafish had been studied. In our study, we
      identified and characterized the full-length miiuy croaker (Miichthys miiuy) DC
      SIGN (mmDC-SIGN) and L-SIGN (mmL-SIGN) genes. The sequence analysis results
      showed that mmDC-SIGN and mmL-SIGN have the same domains with other vertebrates
      except primates, and share some conserved motifs in CRD among all the vertebrates
      which play a crucial role in interacting with Ca(2+) and for recognizing mannose
      containing motifs. Gene synteny of DC-SIGN and L-SIGN were analyzed for the first
      time and gene synteny of L-SIGN was conserved among the five fishes.
      Interestingly, one gene next to L-SIGN from gene synteny had high similarity with
      L-SIGN gene that was described as L-SIGN-like in fish species. While only one L
      SIGN gene existed in other vertebrates, two L-SIGN in fish may be in consequence
      of the fish-specific genome duplication to adapt the specific environment. The
      evolutionary analysis showed that the ancestral lineages of L-SIGN gene in fishes
      experienced purifying selection and the current lineages of L-SIGN gene in fishes
      underwent positive selection, indicating that the ancestral lineages and current
      lineages of L-SIGN gene in fishes underwent different evolutionary patterns. Both
      mmDC-SIGN and mmL-SIGN were expressed in all tested tissues and ubiquitously up
      regulated in infected liver, spleen and kidney at different sampling time points,
      indicating that the mmDC-SIGN and mmL-SIGN participated in the immune response to
      defense against bacteria infection. 

PMID- 25596148
TI  - Decreased numbers of endothelial progenitor cells in patients in the early stages
      of systemic sclerosis.
AB  - INTRODUCTION: Microangiopathy and endothelial dysfunction are present in the
      early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by
      bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the
      vascular abnormalities found in SSc. OBJECTIVES: To evaluate the circulating EPC
      levels and EPC subtypes via flow cytometry and early outgrowth colony-forming
      units (CFUs) in patients with SSc compared to healthy subjects. METHODS: Thirty
      nine female SSc patients (30 in the early stages of SSc) and 44 age-matched
      healthy women were included. Peripheral blood EPCs were quantified using flow
      cytometry and by counting the early outgrowth CFUs. RESULTS: The EPCs quantified
      with flow cytometry and the CFU numbers were significantly lower in SSc patients
      than in control subjects (155.1 +/- 95.1 vs. 241.3 +/- 184.2 EPC/10(6)
      lymphomononuclear cells, p=0.011; 15.4 +/- 8.6 vs. 23.5 +/- 10.9 CFU, p<0.001;
      respectively), as well as in the group of patients in the early stages of SSc
      compared to the controls. Patients with digital ulcers had significantly higher
      CFU counts than those without ulcers (p=0.013). Among patients with the
      scleroderma pattern on nailfold capillaroscopy, patients with the late pattern
      had significantly lower EPC levels than those with the early and active patterns
      (p=0.046). There were no significant correlations of EPCs or CFU levels with RP
      duration. CONCLUSIONS: The present study revealed decreased EPCs in SSc patients,
      including those with early disease onset. These findings suggest that defective
      vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might
      be an important therapeutic target for the prevention of vascular complications
      in SSc patients.

PMID- 25596147
TI  - Wogonin increases beta-amyloid clearance and inhibits tau phosphorylation via
      inhibition of mammalian target of rapamycin: potential drug to treat Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Many
      molecular lesions have been detected in AD, of which the most commonly observed
      is the accumulation of misfolded proteins, including beta-amyloid (Abeta40 and
      Abeta42) and tau, in the aging brain. The mammalian target of rapamycin (mTOR)
      pathway mediates Abeta clearance through autophagy and regulates tau
      phosphorylation via glycogen synthase kinase-3beta (GSK3beta). Thus, mTOR becomes
      an important therapeutic target for AD. However, no mTOR inhibitor has yet been
      marketed to treat AD. Here, we discovered a natural product, wogonin, which could
      potently promote Abeta clearance in the primary neural astrocytes and
      significantly decrease Abeta secretion in SH-SY5Y-APP and BACE1 cells [SH-SY5Y
      cells stably expressing the human amyloid precursor protein (APP) and beta
      secretase (BACE1)] through the mTOR/autophagy signaling pathway. Additionally,
      further research revealed that wogonin inhibited the activity of GSK3beta via
      mTOR inhibition, finally leading to tau phosphorylation reduction in SH-SHY5Y
      cells and primary neural astrocytes. In conclusion, our study identified a small
      molecule, wogonin, which could effectively promote Abeta clearance and decrease
      tau phosphorylation, and highlighted its therapeutic potential for AD treatment.

PMID- 25596149
TI  - Vector-borne pathogens in arctic foxes, Vulpes lagopus, from Canada.
AB  - Because of the relatively low biodiversity within arctic ecosystems, arctic
      foxes, Vulpes lagopus, could serve as sentinels for the study of changes in the
      ecology of vector-borne zoonotic pathogens. The objective of this study was to
      determine the molecular prevalence of 5 different genera of vector borne
      pathogens (Anaplasma, Babesia, Bartonella, Ehrlichia, and Hemotropic Mycoplasma
      spp.) using blood collected from 28 live-trapped arctic foxes from the region of
      Karrak Lake, Nunavut, Canada. Bartonella henselae (n = 3), Mycoplasma haemocanis
      (n = 1), Ehrlichia canis (n = 1), and an Anaplasma sp. (n = 1) DNA were PCR
      amplified and subsequently identified by sequencing. This study provides
      preliminary evidence that vector borne pathogens, not typically associated with
      the arctic ecosystem, exist at low levels in this arctic fox population, and that
      vector exposure, pathogen transmission dynamics, and changes in the geographic
      distribution of pathogens over time should be investigated in future studies. 

PMID- 25596150
TI  - The effect of dietary nitrate supplementation on the oxygen cost of cycling,
      walking performance and resting blood pressure in individuals with chronic
      obstructive pulmonary disease: A double blind placebo controlled, randomised
      control trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) results in exercise
      intolerance. Dietary nitrate supplementation has been shown to lower blood
      pressure (BP), reduce the oxygen cost of exercise, and enhance exercise tolerance
      in healthy volunteers. This study assessed the effects of dietary nitrate on the
      oxygen cost of cycling, walking performance and BP in individuals with mild
      moderate COPD. METHODS: Thirteen patients with mild-moderate COPD were recruited.
      Participants consumed 70 ml of either nitrate-rich (6.77 mmol nitrate; beetroot
      juice) or nitrate-depleted beetroot juice (0.002 mmol nitrate; placebo) twice a
      day for 2.5 days, with the final supplement ~3 hours before testing. BP was
      measured before completing two bouts of moderate-intensity cycling, where
      pulmonary gas exchange was measured throughout. The six-minute walk test (6 MWT)
      was completed 30 minutes subsequent to the second cycling bout. RESULTS: Plasma
      nitrate concentration was significantly elevated following beetroot juice vs.
      placebo (placebo; 48 +/- 86 vs. beetroot juice; 215 +/- 84 uM, P = 0.002). No
      significant differences were observed between placebo vs. beetroot juice for
      oxygen cost of exercise (933 +/- 323 vs. 939 +/- 302 ml: min(-1); P = 0.88),
      distance covered in the 6 MWT (456 +/- 86 vs. 449 +/- 79 m; P = 0.37), systolic
      BP (123 +/- 14 vs. 123 +/- 14 mmHg; P = 0.91), or diastolic BP (77 +/- 9 vs. 79
      +/- 9 mmHg; P = 0.27). CONCLUSION: Despite a large rise in plasma nitrate
      concentration, two days of nitrate supplementation did not reduce the oxygen cost
      of moderate intensity cycling, increase distance covered in the 6 MWT, or lower
      BP.

PMID- 25596151
TI  - Role of food iron fortification on hemoglobin status.

PMID- 25596152
TI  - Genetic Diagnosis in an Indian Child with Alagille Syndrome.

PMID- 25596153
TI  - Subjective global assessment of nutritional status - A systematic review of the
      literature.
AB  - BACKGROUND & AIMS: Subjective Global Assessment (SGA) is a nutritional assessment
      tool widely used in hospital clinical practice, even though it is not exempted of
      limitations in relation to its use. This systematic review intended to update
      knowledge on the performance of SGA as a method for the assessment of the
      nutritional status of hospitalized adults. METHODS: PubMed data base was
      consulted, using the search term "subjective global assessment". Studies
      published in English, Portuguese or Spanish, between 2002 and 2012 were selected,
      excluding those not found in full, letters to the editor, pilot studies,
      narrative reviews, studies with n < 30, studies with population younger than 18
      years of age, research with non-hospitalized populations or those which used a
      modified version of the SGA. RESULTS: Of 454 eligible studies, 110 presented
      eligibility criteria. After applying the exclusion criteria, 21 studies were
      selected, 6 with surgical patients, 7 with clinical patients, and 8 with both.
      Most studies demonstrated SGA performance similar or better than the usual
      assessment methods for nutritional status, such as anthropometry and laboratory
      data, but the same result was not found when comparing SGA and nutritional
      screening methods. CONCLUSIONS: Recently published literature demonstrates SGA as
      a valid tool for the nutritional diagnosis of hospitalized clinical and surgical
      patients, and point to a potential superiority of nutritional screening methods
      in the early detection of malnutrition.

PMID- 25596154
TI  - Reduction in hospital admissions with the addition of prophylactic intramuscular
      ceftriaxone before transrectal ultrasonography-guided prostate biopsies.
AB  - OBJECTIVE: To evaluate the hospitalization rates in 2 pre-prostate biopsy
      antibiotic protocols. METHODS: Two prebiopsy protocols were compared. CiproAlone
      required ciprofloxacin 500 mg twice daily starting 1 day before biopsy and
      continuing for 3 days after biopsy (4 days total). Diabetic patients were
      prescribed ciprofloxacin for 4 days after biopsy. CiproCeft required 1 dose of
      oral ciprofloxacin 500 mg 1 hour before the biopsy and ceftriaxone 1 g
      intramuscular at the time of the biopsy. Hospitalization rates between the
      CiproAlone vs CiproCeft protocols were examined. RESULTS: A total of 4134
      biopsies were identified-2093 in the CiproAlone cohort and 2041 in the CiproCeft
      cohort. The post-prostate biopsy infection hospitalization rate was 0.6% (14
      patients) in the CiproAlone group vs 0.0% (0 patients) in the CiproCeft group (P
      <.0001). Of the patients hospitalized, 12 fit systemic inflammatory response
      syndrome (SIRS) criteria. Eight of 14 hospitalized patients fit the sepsis (SIRS
      and source of infection) criteria. Positive cultures (urine and/or blood)
      resulted from 71% (n = 10) of hospitalized patients. Antibiotic resistance was
      analyzed. Diabetes mellitus was associated with hospitalization after prostate
      biopsy (P = .01) in our population, but there was no difference between the 2
      groups in the rates of diabetes mellitus (P = .46). Patient age, prostate
      specific antigen level, number of biopsy cores obtained, race, and previous
      antibiotics exposure were not found to be independent predictors of post
      transrectal ultrasonography biopsy hospitalization for infection using a
      multivariate regression analysis. CONCLUSION: A prophylactic prebiopsy protocol
      including 2 classes of antibiotics, single-dose ciprofloxacin, and single-dose
      intramuscular ceftriaxone reduced post-transrectal ultrasonography biopsy rates
      of hospitalizations compared to oral ciprofloxacin alone.

PMID- 25596155
TI  - Editorial comment.

PMID- 25596156
TI  - Effects of centrally injected glucagon-like peptide-2 on gastric mucosal blood
      flow in rats: possible mechanisms.
AB  - "Glucagon-like peptide-2" (GLP-2) is a peptide that is released from the
      enteroendocrine L cells in response to food in the gastrointestinal tract.
      Peripheral injection of GLP-2 has been shown to increase gastrointestinal blood
      flow, but effects of central GLP-2 on any vascular bed has not been studied yet.
      The aim of this study is to investigate the effects of various doses of
      intracerebroventricularly (i.c.v.)-injected GLP-2 on gastric mucosal blood flow
      (GMBF) and contribution of calcitonin gene related peptide (CGRP), nitric oxide
      synthase-nitric oxide (NOS-NO) and cyclooxygenase-prostaglandin (COX-PG) systems
      to the possible effect. The gastric chamber technique was used to determine GMBF.
      Urethane anesthesia was used throughout the recording procedure. Male Wistar rats
      were treated with GLP-2 (100, 150 ve 200ng/10MUl; i.c.v.) or saline (10MUl;
      i.c.v.) in order to find out the effective dose of i.c.v. GLP-2 on GMBF. Then,
      CGRP receptor antagonist CGRP-(8-37) (10MUg/kg; s.c.), NOS inhibitor NG-nitro-l
      arginine methyl ester (l-NAME; 30mg/kg; s.c.) or COX inhibitor indomethacin
      (5mg/kg; i.p.) was injected before the effective dose of i.c.v. GLP-2. GMBF was
      measured continuously for 35min following GLP-2 and recorded every fifth minute.
      Non-parametric Kruskal-Wallis test was used for statistical analysis. Differences
      were considered to be significant at p<0.05. GMBF increased rapidly following
      100ng GLP-2 injection and did not fall to the basal levels during 35min. Other
      doses of i.c.v. GLP-2 did not produce any significant difference in GMBF. CGRP
      receptor antagonist, CGRP-(8-37) (10MUg/kg; s.c.) and COX inhibitor indomethacin
      (5mg/kg; i.p.) significantly prevented the increase in GMBF due to GLP-2 (100ng;
      i.c.v.), while l-NAME (30mg/kg; s.c.) was ineffective. None of the drugs produced
      a significant change in GMBF when administered alone. Thus we suggest that,
      i.c.v. GLP-2 increases GMBF and CGRP and endogenous prostaglandins but not NO,
      contribute to this effect. 

PMID- 25596157
TI  - MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that act as
      post-transcriptional regulators. We analysed the in vivo effect of miRNA-124 (miR
      124, the rat analogue of human miR-124a) on adjuvant-induced arthritis (AIA) in
      rats. METHODS: AIA was induced in Lewis rats by injecting incomplete Freund's
      adjuvant with heat-killed Mycobacterium tuberculosis. Precursor (pre)-miR-124 was
      injected into the right hind ankle on day 9. Morphological changes in the ankle
      joint were assessed by micro-CT and histopathology. Cytokine expression was
      examined by western blotting and real-time RT-PCR. The effect of miR-124 on
      predicted target messenger RNAs (mRNAs) was examined by luciferase reporter
      assays. The effect of pre-miR-124 or pre-miR-124a on the differentiation of human
      osteoclasts was examined by tartrate-resistant acid phosphatase staining.
      RESULTS: We found that miR-124 suppressed AIA in rats, as demonstrated by
      decreased synoviocyte proliferation, leucocyte infiltration and cartilage or bone
      destruction. Osteoclast counts and expression level of receptor activator of the
      nuclear factor kappaB ligand (RANKL), integrin beta1 (ITGB1) and nuclear factor
      of activated T cells cytoplasmic 1 (NFATc1) were reduced in AIA rats treated with
      pre-miR-124. Luciferase analysis showed that miR-124 directly targeted the 3'UTR
      of the rat NFATc1, ITGB1, specificity protein 1 and CCAAT/enhancer-binding
      protein alpha mRNAs. Pre-miR-124 also suppressed NFATc1 expression in RAW264.7
      cells. Both miR-124 and miR-124a directly targeted the 3'-UTR of human NFATc1
      mRNA, and both pre-miR-124 and pre-miR-124a suppressed the differentiation of
      human osteoclasts. CONCLUSIONS: We found that miR-124 ameliorated AIA by
      suppressing critical prerequisites for arthritis development, such as RANKL and
      NFATc1. Thus, miR-124a is a candidate for therapeutic use for human rheumatoid
      arthritis.

PMID- 25596158
TI  - A randomised trial of a brace for patellofemoral osteoarthritis targeting knee
      pain and bone marrow lesions.
AB  - OBJECTIVE: Braces used to treat (PF) osteoarthritis (OA) may reduce contact
      stress across the PF joint. We hypothesised that in PF OA, braces would decrease
      knee pain and shrink PF bone marrow lesions (BMLs). METHODS: Eligible subjects
      had painful PF OA. Subjects were randomly allocated to brace or no brace for 6
      weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post
      contrast fat suppressed sagittal and proton density weighted axial images. The
      primary symptom outcome was change in pain at 6 weeks during a preselected
      painful activity, and the primary structural outcome was BML volume change in the
      PF joint. Analyses used multiple linear regression. RESULTS: We randomised 126
      subjects aged 40-70 years (mean age 55.5  years; 72 females (57.1%)). Mean
      nominated visual analogue scale (0-10 cm) pain score at baseline was 6.5 cm. 94
      knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4
      h/day. 6 subjects withdrew during the trial. After accounting for baseline
      values, the brace group had lower knee pain than the control group at 6 weeks
      (difference between groups -1.3 cm, 95% CI -2.0 to -0.7; p<0.001) and reduced PF
      BML volume (difference -490.6 mm(3), 95% CI -929.5 to -51.7; p=0.03) but not
      tibiofemoral volume (difference -53.9 mm(3), 95% CI -625.9 to 518.2; p=0.85).
      CONCLUSIONS: A PF brace reduces BML volume in the targeted compartment of the
      knee, and relieves knee pain. TRIAL REGISTRATION NUMBER: UK. ISRCTN50380458.

PMID- 25596165
TI  - Furan-based acetylating agent for the chemical modification of proteins.
AB  - We have synthesized a furan-based acetylating agent, 2,5-bisacetoxymethylfuran
      (BAMF) from carbohydrate derived 5-hydroxymethylfurfural (HMF) and studied its
      acetylation activity with amines and cytochrome c. The results show that BAMF can
      modify proteins in biological conditions without affecting their structure and
      function. The modification of cytochrome c with BAMF occurred through the
      reduction of heme center, but there was no change in the coordination property of
      iron and the tertiary structure of cytochrome c. Further analysis using MALDI-TOF
      MS spectrometer suggests that BAMF selectively targeted lysine amino acid of
      cytochrome c under our experimental conditions. Kinetics study revealed that the
      modification of cytochrome c with BAMF took place at faster rates than aspirin. 

PMID- 25596159
TI  - Different staining patterns of ovarian Brenner tumor and the associated mucinous
      tumor.
AB  - The association of ovarian Brenner tumors and adjacent mucinous tumors is well
      known but not completely understood. In this study, we analyzed
      immunohistochemical markers on Brenner tumors and their associated mucinous tumor
      to explore Mullerian as well as Wolffian and germ cell derivation and determine
      if the mucinous component is independent or related to the Brenner tumor. Of 32
      consecutive cases of Brenner tumors, 8 were identified with significant mucinous
      component, and 7 additional cases included foci of mucinous epithelium within the
      Brenner transitional nests. All Brenner tumors were diffusely positive for GATA3
      and negative for Paired box gene 8, PAX2, and Sal-like protein 4. Interestingly,
      the areas of mucinous epithelium as well as mucinous tumors, intermixed and
      adjacent to the Brenner tumor, were negative for all 4 markers; however,
      occasional basal-like cells retained expression of GATA3. The immunoprofile of
      mucinous tumors associated with Brenner tumors shares the lack of Mullerian
      markers PAX2 and Paired box gene 8 with the Brenner tumor but differs in the
      expression of GATA3 only in the Brenner tumor component. 

PMID- 25596166
TI  - Discovery of 3H-imidazo[4,5-c]quinolin-4(5H)-ones as potent and selective
      dipeptidyl peptidase IV (DPP-4) inhibitors: use of a carboxylate prodrug to
      improve bioavailability.
AB  - We have previously reported a novel series of 3H-imidazo[4,5-c]quinolin-4(5H)
      ones with potent dipeptidyl peptidase IV (DPP-4) inhibitory activity. However,
      these compounds showed poor oral absorption. We attempted in this study
      esterification of the carboxylic acid moiety to improve the compounds 1-4 plasma
      concentrations. Our efforts yielded 10h with a 5-methyl-2-oxo-1,3-dioxol-4-yl
      methyl ester as an S9/plasma-cleavable functionality. Compound 10h showed
      significantly high oral absorption and potent DPP-4 inhibition in vivo and
      decreased Zucker fatty rats glucose levels in the oral glucose tolerance test.
      Optimization of the ester moiety revealed that rapid conversion to the carboxyl
      form in both liver S9 fractions and serum was important for prodrugs not to be
      detected in the plasma after oral administration. In particular, lability in the
      serum was found to be an important characteristic. Through our investigation, we
      were able to develop a novel efficient synthetic method for construction of 3H
      imidazo[4,5-c]quinolin-4(5H)-ones using intramolecular radical cyclization. 

PMID- 25596167
TI  - Synthesis and functionalization of bicyclic N,O-acetal scaffolds from furfural.
AB  - We have synthesized biologically relevant 6-aza-8-oxa[3.2.1]bicyclooctane
      scaffolds in a five-step procedure starting from furfural. Besides showing that
      these scaffolds are amenable to decoration via standard functional group
      interconversions, we also describe investigations for further functionalization
      via Lewis acid-mediated N,O-acetal opening, followed by nucleophilic trapping of
      the resulting intermediate cation. By using different nucleophiles, we have
      successfully prepared a modest library of 2,6-trans-disubstituted pyrans in good
      yields and in a highly diastereoselective manner. 

PMID- 25596168
TI  - 2-Aminophenanthroline dimer stabilized the C-C mismatched duplex DNA.
AB  - New ligands with three-ring system for the recognition of a cytosine bulge and a
      cytosine-cytosine mismatch were designed and synthesized. The 2-amino-1,10
      phenanthroline was selected as a recognition unit among the possible three-ring
      systems of a parent recognition unit of 2-amino-1,8-naphthyridine. The 3
      aminopropanamide of 2-amino-1,10-phenanthroline (APM) bound to the cytosine bulge
      DNA. Other single nucleotide bulges were stabilized by the ligand with much lower
      efficiency. The dimer APD consisting of two molecules of APM was found to
      stabilize the C-C mismatch DNA selectively. Structure-activity relationship
      studies revealed that the APD-binding to the C-C mismatch DNA required both
      phenanthroline heterocycles in a molecule. 

PMID- 25596169
TI  - Synthesis of 6-[(11)C]methyl-m-tyrosine ([(11)C]6MemTyr) for dopamine synthesis
      imaging in living brain using PET.
AB  - A novel PET probe, 6-[(11)C]methyl-m-tyrosine ([(11)C]6MemTyr), was developed for
      quantitative imaging of presynaptic dopamine (DA) synthesis in the living brain
      using positron emission tomography (PET). This probe was evaluated by comparison
      with conventional 6-[(18)F]fluoro-l-dopa ([(18)F]FDOPA). [(11)C]6MemTyr was
      labeled using rapid Pd(0)-mediated C-[(11)C]methylation with [(11)C]methyl
      iodide. The synthesis time was only 35min, and its radiochemical yield was 76%,
      with radiochemical purity of >99%. PET measurements indicated that [(11)C]6MemTyr
      could image presynaptic DA synthesis in the striatum of living monkey brain,
      providing much higher contrast between the striatum and the cerebellum than that
      with [(18)F]FDOPA. 

PMID- 25596170
TI  - A mobile app to aid smoking cessation: preliminary evaluation of SmokeFree28.
AB  - BACKGROUND: Little is known about the effectiveness of mobile apps in aiding
      smoking cessation or their validity for automated collection of data on smoking
      cessation outcomes. OBJECTIVE: We conducted a preliminary evaluation of SF28
      (SF28 is the name of the app, short for SmokeFree28)-an app aimed at helping
      smokers to be smoke-free for 28 days. METHODS: Data on sociodemographic
      characteristics, smoking history, number of logins, and abstinence at each login
      were uploaded to a server from SF28 between August 2012 and August 2013. Users
      were included if they were aged 16 years or over, smoked cigarettes at the time
      of registration, had set a quit date, and used the app at least once on or after
      their quit date. Their characteristics were compared with data from a
      representative sample of smokers trying to stop smoking in England. The
      percentage of users recording 28 days of abstinence was compared with a value of
      15% estimated for unaided quitting. Correlations were assessed between recorded
      abstinence for 28 days and well-established abstinence predictors. RESULTS: A
      total of 1170 users met the inclusion criteria. Compared with smokers trying to
      quit in England, they had higher consumption, and were younger, more likely to be
      female, and had a non-manual rather than manual occupation. In total, 18.9% (95%
      CI 16.7-21.1) were recorded as being abstinent from smoking for 28 days or
      longer. The mean number of logins was 8.5 (SD 9.0). The proportion recording
      abstinence for 28 days or longer was higher in users who were older, in a non
      manual occupation, and in those using a smoking cessation medication.
      CONCLUSIONS: The recorded 28-day abstinence rates from the mobile app, SF28,
      suggest that it may help some smokers to stop smoking. Further evaluation by
      means of a randomized trial appears to be warranted.

PMID- 25596171
TI  - Inhalation analgesia with nitrous oxide versus other analgesic techniques in
      hysteroscopic polypectomy: a pilot study.
AB  - STUDY OBJECTIVE: To show the decrease in pain and better tolerance to inhalation
      analgesia with a 50% equimolar mixture of nitrogen protoxide and oxygen in
      hysteroscopic polypectomy compared with paracervical anesthesia and a control
      group. DESIGN: One hundred six patients scheduled for office hysteroscopy and
      polypectomy were divided into the following 3 groups: the control group, the
      nitrous oxide group, and the paracervical infiltration group. Patients were
      assigned sequentially (Canadian Task Force classification II-1). SETTING: The
      study took place in a hysteroscopy outpatient clinic under the supervision of a
      gynecologist and 2 nurses trained to cooperate in the trial. PATIENTS: One
      hundred six women from Area III of Madrid Community, Spain, who had been
      diagnosed with endometrial polyps at a gynecology office and were scheduled for
      office hysteroscopy and polypectomy agreed to participate in the study.
      INTERVENTIONS: Patients in group 1 (control group) received no treatment. Group 2
      received inhaled nitrous oxide and group 3 paracervical infiltration with 1%
      lidocaine. MEASUREMENTS AND MAIN RESULTS: Pain was assessed using the visual
      analog scale (0-10). Pain perceived by patients was lower in the nitrous Oxide
      group (mean: 3.55 +/- 0.60, median: 3) versus the control group (mean: 5.49 +/-
      1.88, median: 6, p < .05) and the paracervical infiltration group (mean: 4.22 +/-
      1.73, median: 5). Tolerance to pain, assessed by the medical staff using
      qualitative variables, was bad for the control group, very good for the nitrous
      oxide group, and good for the paracervical infiltration group (p < .05). There
      were no complications in 82% of the patients in the nitrous oxide group, whereas
      in the paracervical infiltration group, there were complications in more than 50%
      of the patients. No severe complications occurred. CONCLUSION: Nitrous oxide is a
      safe and effective analgesic technique for polipectomy office hysteroscopy
      compared with the paracervical infiltration and control groups.

PMID- 25596172
TI  - Robotic Single-site Technique Allows Pelvic Lymphadenectomy in Surgical Staging
      of Endometrial Cancer.

PMID- 25596173
TI  - Diagnosis of community-acquired acute respiratory illness: From conventional
      microbiological methods to molecular detection (multiplex).
AB  - Investigations of the etiologic agents of community-acquired acute respiratory
      illness may lead to better treatment decisions and patient outcomes. In a routine
      care setting, we assessed the diagnostic performance of a multiplex PCR assay
      with respect to conventional microbiological methods, in a continuous series of
      adult cases of community-acquired acute respiratory illness. We enrolled 279
      adult patients hospitalised for community-acquired acute respiratory illness at
      Tours University Hospital during the winter of 2011-2012. Respiratory samples
      (mostly nasopharyngeal aspirates) were studied prospectively by indirect
      immunofluorescence assay and multiplex PCR, that enable detection of 8 viruses
      and 21 respiratory pathogens respectively. In total, 255 of the 279 (91.4%)
      samples had interpretable results by both methods. At least one respiratory
      pathogen was detected by multiplex PCR in 171 specimens (65%). Overall, 130 (76%)
      of the 171 positive samples were positive for only one respiratory pathogen, 37
      (22%) samples were positive for two pathogens and four (2%) were positive for
      three pathogens. With indirect immunofluorescence assay, a respiratory virus was
      detected in 27 of the 255 (11%) specimens. Indirect immunofluorescence assay
      detected some of the influenza virus A (15/51, 29%) infections identified by
      multiplex PCR and some (7/15, 47%) human metapneumovirus and (5/12, 42%)
      respiratory syncytial virus infections, but it did not detect all the adenovirus
      infections. Thus, access to multiplex molecular assays improves the diagnostic
      spectrum and accuracy over conventional methods, increasing the frequency of
      identification of the respiratory pathogens involved in community-acquired acute
      respiratory illness. 

PMID- 25596174
TI  - Hippocampal dysfunctions caused by cranial irradiation: a review of the
      experimental evidence.
AB  - Cranial irradiation (IR) is commonly used for the treatment of brain tumors but
      may cause disastrous brain injury, especially in the hippocampus, which has
      important cognition and emotional regulation functions. Several preclinical
      studies have investigated the mechanisms associated with cranial IR-induced
      hippocampal dysfunction such as memory defects and depression-like behavior.
      However, current research on hippocampal dysfunction and its associated
      mechanisms, with the ultimate goal of overcoming the side effects of cranial
      radiation therapy in the hippocampus, is still very much in progress. This
      article reviews several in vivo studies on the possible mechanisms of radiation
      induced hippocampal dysfunction, which may be associated with hippocampal
      neurogenesis, neurotrophin and neuroinflammation. Thus, this review may be
      helpful to gain new mechanistic insights into hippocampal dysfunction following
      cranial IR and provide effective strategies for potential therapeutic approaches
      for cancer patients receiving radiation therapy. 

PMID- 25596175
TI  - Being female is a risk factor for chronic pain. Are inflammatory processes to
      blame?

PMID- 25596178
TI  - The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in
      mice.
AB  - BACKGROUND AND AIMS: Gata6 is required to complete and maintain acinar
      differentiation in the mouse pancreas. Pancreas-specific Gata6 ablation during
      development causes extensive and persistent acinar-ductal metaplasia, which is
      considered an initial step of mutant KRas-driven carcinogenesis. Therefore, the
      Gata6-null pancreas might represent a tumour-prone environment. We investigated
      whether Gata6 plays a role during pancreatic tumorigenesis. DESIGN: We analysed
      genetically engineered mouse models and human pancreatic ductal adenocarcinoma
      (PDAC) cell lines, using a combination of histopathological studies, genome-wide
      expression and chromatin immunoprecipitation experiments to understand the role
      of Gata6 in the initiation and progression of KRas(G12V)-driven tumours RESULTS:
      We show that Gata6 maintains the acinar differentiation programme, both directly
      and indirectly, and it concomitantly suppresses ectopic programmes in the
      pancreas. Gata6 ablation renders acinar cells more sensitive to KRas(G12V),
      thereby accelerating tumour development. Gata6 expression is spontaneously lost
      in a mouse model of KRas(G12V)-driven PDAC, in association with altered cell
      differentiation. Using a combination of ChIP-Seq and RNA-Seq, we show that Gata6
      exerts its tumour-suppressive effect through the promotion of cell
      differentiation, the suppression of inflammatory pathways, and the direct
      repression of cancer-related pathways. Among them is the epidermal growth factor
      receptor (EGFR) pathway, the activity of which is upregulated in the normal and
      preneoplastic Gata6-null pancreas. Accordingly, GATA6-silencing in human PDAC
      cells leads to an upregulation of EGFR. CONCLUSIONS: We propose that, in the
      pancreas, Gata6 acts as a tumour suppressor by enforcing acinar cell
      differentiation, by directly and indirectly repressing ectopic differentiation
      programmes, and by regulating crucial cancer-related gene expression pathways.

PMID- 25596176
TI  - Effects of chronic interpersonal stress exposure on depressive symptoms are
      moderated by genetic variation at IL6 and IL1beta in youth.
AB  - AIMS: Close to one third of patients with major depression show increases in pro
      inflammatory cytokines, which are in turn associated with risk for inflammatory
      disease. Genetic variants that enhance immune reactivity may thus enhance
      inflammatory and depressive reactions to stress. The aim of the present study was
      to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C,
      rs1800795), IL1beta (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as
      moderators of the relationship between chronic stress exposure and elevations in
      depressive symptoms. METHODS: Participants were 444 Australian youth (mean
      age=20.12) whose exposure to chronic stress in the past 6months was assessed
      using the semi-structured UCLA Life Stress Interview, and who completed the Beck
      Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all
      participants in the selected sample provided blood samples for genotyping.
      RESULTS: In line with a hypothesized moderation effect, -174G allele carriers at
      IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C
      homozygotes with equal interpersonal stress exposure. However, IL6 genotype did
      not moderate the effects of non-interpersonal stress exposure (i.e., financial,
      work and health-related difficulties) on depression. Also in line with
      hypotheses, the -511C allele in IL1beta, previously associated with higher IL
      1beta expression, was associated with more severe depression following chronic
      interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating
      effect was specific to interpersonal stressors and did not generalize to non
      interpersonal stress. TNF was not a moderator of the effects of either
      interpersonal or non-interpersonal stress on later depression outcomes.
      CONCLUSION: Findings were consistent with the hypothesis that pro-inflammatory
      genetic variation increases the risk of stress-induced depression. The present
      results provide evidence of a genetic mechanism contributing to individual
      differences in depressive symptomatology following interpersonal stress exposure.

PMID- 25596179
TI  - Tenofovir monotherapy versus tenofovir and entecavir combination therapy in
      patients with entecavir-resistant chronic hepatitis B with multiple drug failure:
      results of a randomised trial.
AB  - OBJECTIVE: Little clinical data are available regarding the optimal treatment of
      patients who harbour entecavir (ETV)-resistant HBV. DESIGN: In this multicentre
      randomised trial, patients who had HBV with ETV resistance-associated mutations
      and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir
      disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1
      mg/day) combination therapy (n=45) for 48 weeks. RESULTS: Baseline
      characteristics were comparable between groups, including HBV DNA levels (median,
      4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at
      least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and
      rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the
      TDF group completed 48 weeks of treatment. At week 48, the proportion of patients
      with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly
      different between the TDF and TDF+ETV groups (71% vs. 73%; p>0.99). The mean
      change in HBV DNA levels from baseline was not significantly different between
      groups (-3.66 vs. -3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred
      in one patient on TDF, which was attributed to poor drug adherence. At week 48,
      six and three patients in the TDF and TDF+ETV groups, respectively, retained
      their baseline resistance mutations (p>0.99). None developed additional
      resistance mutations. Safety profiles were comparable in the two groups.
      CONCLUSIONS: TDF monotherapy for 48 weeks provided a virological response
      comparable to that of TDF and ETV combination therapy in patients infected with
      ETV-resistant HBV. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID NCT01639092.

PMID- 25596180
TI  - Statins, Rho GTPases and KLF2: new mechanistic insight into liver fibrosis and
      portal hypertension.

PMID- 25596181
TI  - Pleiotrophin regulates the ductular reaction by controlling the migration of
      cells in liver progenitor niches.
AB  - OBJECTIVE: The ductular reaction (DR) involves mobilisation of reactive-appearing
      duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF)
      differentiation of hepatic stellate cells (HSC) in the space of Disse.
      Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate
      the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby
      augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is
      regulated by PTN/PTPRZ1 signalling. DESIGN: PTN-GFP, PTN-knockout (KO), PTPRZ1
      KO, and wild type (WT) mice were examined before and after bile duct ligation
      (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice
      were also treated with PTN to determine effects on downstream signaling
      phosphoproteins, gene expression, growth, and migration. Liver biopsies from
      patients with DRs were also interrogated. RESULTS: Although quiescent HSC and RDC
      lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was
      demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in
      MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal
      accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased
      in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN
      dependent accumulation of phosphoproteins that control cell-cell adhesion and
      migration, with resultant inhibition of cell migration. PTPRZ1-positive cells
      were prominent in the DRs of patients with ductal plate defects and adult
      cholestatic diseases. CONCLUSIONS: PTN, and its receptor, PTPRZ1, regulate the DR
      to liver injury by controlling the migration of resident cells in adult liver
      progenitor niches.

PMID- 25596182
TI  - Spatial variation of the colonic microbiota in patients with ulcerative colitis
      and control volunteers.
AB  - OBJECTIVES: The relevance of spatial composition in the microbial changes
      associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies
      and laser capture microdissection with deep sequencing of the gut microbiota to
      develop an integrated spatial assessment of the microbial community in controls
      and UC. DESIGN: A total of 98 samples were sequenced to a mean depth of 31,642
      reads from nine individuals, four control volunteers undergoing routine
      colonoscopy and five patients undergoing surgical colectomy for medically
      refractory UC. Samples were retrieved at four colorectal locations, incorporating
      the luminal microbiota, mucus gel layer and whole mucosal biopsies. RESULTS:
      Interpersonal variability accounted for approximately half of the total variance.
      Surprisingly, within individuals, asymmetric Eigenvector map analysis
      demonstrated differentiation between the luminal and mucus gel microbiota, in
      both controls and UC, with no differentiation between colorectal regions. At a
      taxonomic level, differentiation was evident between both cohorts, as well as
      between the luminal and mucosal compartments, with a small group of taxa uniquely
      discriminating the luminal and mucosal microbiota in colitis. There was no
      correlation between regional inflammation and a breakdown in this spatial
      differentiation or bacterial diversity. CONCLUSIONS: Our study demonstrates a
      conserved spatial structure to the colonic microbiota, differentiating the
      luminal and mucosal communities, within the context of marked interpersonal
      variability. While elements of this structure overlap between UC and control
      volunteers, there are differences between the two groups, both in terms of the
      overall taxonomic composition and how spatial structure is ascribable to distinct
      taxa.

PMID- 25596183
TI  - Transcriptome and metabolite profiling of the infection cycle of Zymoseptoria
      tritici on wheat reveals a biphasic interaction with plant immunity involving
      differential pathogen chromosomal contributions and a variation on the
      hemibiotrophic lifestyle definition.
AB  - The hemibiotrophic fungus Zymoseptoria tritici causes Septoria tritici blotch
      disease of wheat (Triticum aestivum). Pathogen reproduction on wheat occurs
      without cell penetration, suggesting that dynamic and intimate intercellular
      communication occurs between fungus and plant throughout the disease cycle. We
      used deep RNA sequencing and metabolomics to investigate the physiology of plant
      and pathogen throughout an asexual reproductive cycle of Z. tritici on wheat
      leaves. Over 3,000 pathogen genes, more than 7,000 wheat genes, and more than 300
      metabolites were differentially regulated. Intriguingly, individual fungal
      chromosomes contributed unequally to the overall gene expression changes. Early
      transcriptional down-regulation of putative host defense genes was detected in
      inoculated leaves. There was little evidence for fungal nutrient acquisition from
      the plant throughout symptomless colonization by Z. tritici, which may instead be
      utilizing lipid and fatty acid stores for growth. However, the fungus then
      subsequently manipulated specific plant carbohydrates, including fructan
      metabolites, during the switch to necrotrophic growth and reproduction. This
      switch coincided with increased expression of jasmonic acid biosynthesis genes
      and large-scale activation of other plant defense responses. Fungal genes
      encoding putative secondary metabolite clusters and secreted effector proteins
      were identified with distinct infection phase-specific expression patterns,
      although functional analysis suggested that many have overlapping/redundant
      functions in virulence. The pathogenic lifestyle of Z. tritici on wheat revealed
      through this study, involving initial defense suppression by a slow-growing
      extracellular and nutritionally limited pathogen followed by defense (hyper)
      activation during reproduction, reveals a subtle modification of the conceptual
      definition of hemibiotrophic plant infection. 

PMID- 25596184
TI  - ECERIFERUM2-LIKE proteins have unique biochemical and physiological functions in
      very-long-chain fatty acid elongation.
AB  - The extension of very-long-chain fatty acids (VLCFAs) for the synthesis of
      specialized apoplastic lipids requires unique biochemical machinery. Condensing
      enzymes catalyze the first reaction in fatty acid elongation and determine the
      chain length of fatty acids accepted and produced by the fatty acid elongation
      complex. Although necessary for the elongation of all VLCFAs, known condensing
      enzymes cannot efficiently synthesize VLCFAs longer than 28 carbons, despite the
      prevalence of C28 to C34 acyl lipids in cuticular wax and the pollen coat. The
      eceriferum2 (cer2) mutant of Arabidopsis (Arabidopsis thaliana) was previously
      shown to have a specific deficiency in cuticular waxes longer than 28 carbons,
      and heterologous expression of CER2 in yeast (Saccharomyces cerevisiae)
      demonstrated that it can modify the acyl chain length produced by a condensing
      enzyme from 28 to 30 carbon atoms. Here, we report the physiological functions
      and biochemical specificities of the CER2 homologs CER2-LIKE1 and CER2-LIKE2 by
      mutant analysis and heterologous expression in yeast. We demonstrate that all
      three CER2-LIKEs function with the same small subset of condensing enzymes, and
      that they have different effects on the substrate specificity of the same
      condensing enzyme. Finally, we show that the changes in acyl chain length caused
      by each CER2-LIKE protein are of substantial importance for cuticle formation and
      pollen coat function.

PMID- 25596186
TI  - Deficiency of endothelium-specific transcription factor Sox17 induces
      intracranial aneurysm.
AB  - BACKGROUND: Intracranial aneurysm (IA) is a common vascular disorder that
      frequently leads to fatal vascular rupture. Although various acquired risk
      factors associated with IA have been identified, the hereditary basis of IA
      remains poorly understood. As a result, genetically modified animals accurately
      modeling IA and related pathogenesis have been lacking, and subsequent drug
      development has been delayed. METHODS AND RESULTS: The transcription factor Sox17
      is robustly expressed in endothelial cells of normal intracerebral arteries. The
      combination of Sox17 deficiency and angiotensin II infusion in mice induces
      vascular abnormalities closely resembling the cardinal features of IA such as
      luminal dilation, wall thinning, tortuosity, and subarachnoid hemorrhages. This
      combination impairs junctional assembly, cell-matrix adhesion, regeneration
      capacity, and paracrine secretion in endothelial cells of intracerebral arteries,
      highlighting key endothelial dysfunctions that lead to IA pathogenesis. Moreover,
      human IA samples showed reduced Sox17 expression and impaired endothelial
      integrity, further strengthening the applicability of this animal model to
      clinical settings. CONCLUSIONS: Our findings demonstrate that Sox17 deficiency in
      mouse can induce IA under hypertensive conditions, suggesting Sox17 deficiency as
      a potential genetic factor for IA formation. The Sox17-deficient mouse model
      provides a novel platform to develop therapeutics for incurable IA.

PMID- 25596185
TI  - Crystal structure of human persulfide dioxygenase: structural basis of
      ethylmalonic encephalopathy.
AB  - The ethylmalonic encephalopathy protein 1 (ETHE1) catalyses the oxygen-dependent
      oxidation of glutathione persulfide (GSSH) to give persulfite and glutathione.
      Mutations to the hETHE1 gene compromise sulfide metabolism leading to the genetic
      disease ethylmalonic encephalopathy. hETHE1 is a mono-iron binding member of the
      metallo-beta-lactamase (MBL) fold superfamily. We report crystallographic
      analysis of hETHE1 in complex with iron to 2.6 A resolution. hETHE1 contains an
      alphabetabetaalpha MBL-fold, which supports metal-binding by the side chains of
      an aspartate and two histidine residues; three water molecules complete
      octahedral coordination of the iron. The iron binding hETHE1 enzyme is related to
      the 'classical' di-zinc binding MBL hydrolases involved in antibiotic resistance,
      but has distinctive features. The histidine and aspartate residues involved in
      iron-binding in ETHE1, occupy similar positions to those observed across both the
      zinc 1 and zinc 2 binding sites in classical MBLs. The active site of hETHE1 is
      very similar to an ETHE1-like enzyme from Arabidopsis thaliana (60% sequence
      identity). A channel leading to the active site is sufficiently large to
      accommodate a GSSH substrate. Some of the observed hETHE1 clinical mutations
      cluster in the active site region. The structure will serve as a basis for
      detailed functional and mechanistic studies on ETHE1 and will be useful in the
      development of selective MBL inhibitors. 

PMID- 25596187
TI  - Sexual and functional outcomes of vaginoplasty using acellular porcine small
      intestinal submucosa graft or laparoscopic peritoneal vaginoplasty: a comparative
      study.
AB  - STUDY QUESTION: Can vaginoplasty in patients with Mayer-Rokitansky-Kuster-Hauser
      syndrome (MRKHS) be achieved using an acellular porcine small intestinal
      submucosa (SIS) graft? SUMMARY ANSWER: Vaginoplasty using SIS graft was
      successfully achieved in women with MRKHS, and the anatomical and functional
      outcomes of this procedure were comparable to those of laparoscopic peritoneal
      vaginoplasty. WHAT IS KNOWN ALREADY: There is a great variety of vaginal
      reconstruction techniques, which suggests there is no single superior surgical
      technique. STUDY DESIGN, SIZE, DURATION: This prospective observational study
      included 34 patients with congenital vaginal agenesis who underwent vaginoplasty
      using SIS graft (the SIS group) between December 2011 and July 2013, and 41
      patients with the same disease who underwent laparoscopic peritoneal vaginoplasty
      (the Davydov group) between January 2008 and July 2013. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Patient and surgical data, follow-up information, and the
      female sexual function index (FSFI) scores in the two groups were analysed and
      compared. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with the laparoscopic
      Davydov procedure, the operating time of vaginoplasty using SIS graft was
      significantly shorter, and the estimated blood loss was significantly less.
      Patients in the SIS group had an earlier return of bowel activity, and an earlier
      return to work. However, the total cost in the SIS group was significantly higher
      than that in the Davydov group due to the cost of the SIS graft ($3525 per
      graft). Most patients (28/34 in the SIS group and 37/41 in the laparoscopic
      Davydov group) returned for their follow-up 9 months post-surgery. The mean
      length of the neovagina in the SIS group seemed slightly shorter than that in the
      Davydov group (6.8 +/- 0.9 cm versus 7.3 +/- 1.3 cm, P = 0.081). Thirteen
      patients (46%) in the SIS group and 11 (29%) in the Davydov group had a neovagina
      <7 cm long (P = 0.453), whereas 4 patients (14%) in the SIS group and 3 patients
      (8%) in the Davydov group had a neovagina <6 cm long (P = 0.201). Sixteen
      patients in the SIS group and 25 in the Davydov group subsequently had a sexual
      partner and became sexually active. Four patients in the SIS group and six in the
      Davydov group reported low total FSFI scores (<=23). There was no statistically
      significant difference in the total FSFI scores and the scores of all six domains
      of the FSFI between the two groups. The average time of continuous mould wearing
      in the SIS group was statistically significantly longer than that in the Davydov
      group (7.8 +/- 3.3 months versus 4.8 +/- 1.6 months, P = 0.001). In the patients
      with a neovaginal length of >=6 cm, the FSFI score of the women (26.6 +/- 2.3
      versus 21.5 +/- 1.5, P < 0.001) and the satisfactory score of their partner (8.6
      +/- 1.2 versus 6.6 +/- 1.2, P < 0.001) were both statistically significantly
      higher than patients with a neovaginal length of <6 cm. LIMITATIONS, REASONS FOR
      CAUTION: The main limitation of this study is that it is non-randomized. Further
      randomized studies are warranted to compare the effects of these two procedures.
      WIDER IMPLICATIONS OF THE FINDINGS: Despite the need to wear a mould for longer,
      vaginoplasty using SIS graft provides an attractive, alternative treatment for
      women with MRKHS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by
      the Chinese National Nature Sciences Foundation (grant number 81471416) and the
      National Key Clinical Faculty Construction Program of China. No competing
      interests are declared. TRIAL REGISTRATION NUMBER: N/A.

PMID- 25596189
TI  - Requirements for nutrition support pharmacists.

PMID- 25596190
TI  - Corrigendum.
AB  - Pappas S, Krzywda E, Mcdowell N. Nutrition and pancreaticoduodenectomy. Nutr Clin
      Pract. 2010;25:234-243. (Original DOI: 10.1177/0884533610368709) In this article
      in the June 2010 issue of Nutrition in Clinical Practice, Figures 1-3 were
      reprinted from another source without permission credit lines. The following
      credit line has been added to each figure caption in the online article:
      Reprinted from Evans D, ed. Questions and Answers Pancreatic Cancer. Houston, TX:
      M.D. Anderson: 2008:1, 6-7 with permission from M.D. Anderson. 

PMID- 25596188
TI  - Emerging themes for sensitivity training modules of African healthcare workers
      attending to men who have sex with men: a systematic review.
AB  - Sensitivity training of front-line African health care workers (HCWs) attending
      to men who have sex with men (MSM) is actively promoted through national HIV
      prevention programming in Kenya. Over 970 Kenyan-based HCWs have completed an
      eight-modular online training free of charge (http://www.marps-africa.org) since
      its creation in 2011. Before updating these modules, we performed a systematic
      review of published literature of MSM studies conducted in sub-Saharan Africa
      (sSA) in the period 2011-2014, to investigate if recent studies provided:
      important new knowledge currently not addressed in existing online modules;
      contested information of existing module topics; or added depth to topics covered
      already. We used learning objectives of the eight existing modules to categorise
      data from the literature. If data could not be categorised, new modules were
      suggested. Our review identified 142 MSM studies with data from sSA, including 34
      studies requiring module updates, one study contesting current content, and 107
      studies reinforcing existing module content. ART adherence and community
      engagement were identified as new modules. Recent MSM studies conducted in sSA
      provided new knowledge, contested existing information, and identified new areas
      of MSM service needs currently unaddressed in the online training. 

PMID- 25596191
TI  - Imiquimod 5% cream for five consecutive days a week in an HIV-infected
      observational cohort up to 32 weeks in the treatment of high-grade squamous
      intraepithelial lesions.
AB  - OBJECTIVES: The incidence of anal cancer is increasing especially in HIV-positive
      men having sex with men. Screening for the cancer precursor, high-grade squamous
      intraepithelial lesions (HSIL), is challenging, as current treatment is
      suboptimal. The aim of this prospective study was to establish the efficacy of
      five consecutive days a week self-administered treatment with imiquimod 5% cream
      for both perianal and intra-anal HSIL and to assess the adverse effects and
      burden of this regimen. METHODS: 44 patients with histologically proved perianal
      or intra-anal HSIL were treated with a five consecutive days a week imiquimod 5%
      cream regimen. When no response could be confirmed after the first 16 weeks of
      therapy, patients were encouraged to continue the use of the cream for a further
      16 weeks. Side effects were routinely assessed. RESULTS: Complete or partial
      response was observed in 20 (45%) of 44 patients with HSIL after 16 weeks of
      treatment; another nine patients showed complete or partial response after an
      additional 16 weeks of treatment, resulting in a response rate of 29 (66%) out of
      44 patients. CONCLUSIONS: Topical imiquimod 5% cream is useful in HSIL. A five
      consecutive days treatment regimen with imiquimod 5% cream for HSIL does not seem
      to be more effective compared with the customary prescription for 3 days a week.
      A prolonged course of imiquimod 5% cream is warranted for intra-anal HSIL.
      Adverse effects are comparable between 3 and 5 days treatment regimen.

PMID- 25596192
TI  - Oral and anal sex are key to sustaining gonorrhoea at endemic levels in MSM
      populations: a mathematical model.
AB  - OBJECTIVES: Despite early treatment of urethral infection, gonorrhoea is endemic
      in urban populations of men who have sex with men (MSM) in Australia. By
      contrast, gonorrhoea is not common in urban heterosexual populations. Sexual
      activities among MSM usually involve anal or oral sex, and as these behaviours
      are becoming increasingly common among heterosexuals, there is a need to
      investigate their roles in transmission of gonorrhoea. METHODS: We developed
      individual-based models of transmission of gonorrhoea in MSM and heterosexuals
      that incorporate anatomical site-specific transmission of gonorrhoea. We
      estimated the probabilities of transmission for anal sex and oral sex by
      calibrating an MSM model against prevalence of gonorrhoea and sexual activity
      data. These probabilities were then applied to a heterosexual model in order to
      examine whether gonorrhoea can persist in a heterosexual population through the
      addition of anal sex and oral sex. RESULTS: In the MSM model, gonorrhoea can
      persist despite prompt treatment of urethral infections. The probability of
      gonorrhoea persisting is reduced if use of condom for oral sex is increased to
      more than 15% of acts. Assuming that treatment of symptomatic infections is
      prompt, gonorrhoea is unlikely to persist in a heterosexual population even with
      the addition of anal and oral sex. CONCLUSIONS: Our models suggest that oral sex
      has an important role in sustaining gonorrhoea in a population of MSM by
      providing a pool of untreated asymptomatic infection. The importance of anal sex
      or oral sex in sustaining gonorrhoea in a heterosexual population remains
      uncertain due to the lack of information linking different types of sex acts and
      transmissibility.

PMID- 25596194
TI  - Initiation of exemestane in two warfarin-treated patients leading to elevation
      and variability of INR.
AB  - Aromatase inhibitors are sometimes chosen for adjuvant therapy in post-menopausal
      breast cancer patients with a history of venous thromboembolism over an
      antiestrogen due to the lower risk of venous thromboembolism associated with
      aromatase inhibitors compared to antiestrogens. We report two cases where
      patients on warfarin therapy had an increase in their international normalized
      ratio with the initiation of exemestane therapy. Initially, the patients also
      showed international normalized ratio variability possibly due to variable
      absorption of exemestane. We suggest patients being treated with warfarin and
      exemestane concomitantly need close monitoring and education in order to decrease
      the risk of adverse events that could be associated with this possible
      interaction. To our knowledge, there are no similar reported cases in the
      literature. 

PMID- 25596195
TI  - Electroencephalography as a clinical tool for diagnosing and monitoring attention
      deficit hyperactivity disorder: a cross-sectional study.
AB  - OBJECTIVES: The aim of this study was to develop and test, for the first time, a
      multivariate diagnostic classifier of attention deficit hyperactivity disorder
      (ADHD) based on EEG coherence measures and chronological age. SETTING: The
      participants were recruited in two specialised centres and three schools in
      Reykjavik. PARTICIPANTS: The data are from a large cross-sectional cohort of 310
      patients with ADHD and 351 controls, covering an age range from 5.8 to 14 years.
      ADHD was diagnosed according to the Diagnostic and Statistical Manual of Mental
      Disorders fourth edition (DSM-IV) criteria using the K-SADS-PL semistructured
      interview. Participants in the control group were reported to be free of any
      mental or developmental disorders by their parents and had a score of less than
      1.5 SDs above the age-appropriate norm on the ADHD Rating Scale-IV. Other than
      moderate or severe intellectual disability, no additional exclusion criteria were
      applied in order that the cohort reflected the typical cross section of patients
      with ADHD. RESULTS: Diagnostic classifiers were developed using statistical
      pattern recognition for the entire age range and for specific age ranges and were
      tested using cross-validation and by application to a separate cohort of
      recordings not used in the development process. The age-specific classification
      approach was more accurate (76% accuracy in the independent test cohort; 81%
      cross-validation accuracy) than the age-independent version (76%; 73%).
      Chronological age was found to be an important classification feature.
      CONCLUSIONS: The novel application of EEG-based classification methods presented
      here can offer significant benefit to the clinician by improving both the
      accuracy of initial diagnosis and ongoing monitoring of children and adolescents
      with ADHD. The most accurate possible diagnosis at a single point in time can be
      obtained by the age-specific classifiers, but the age-independent classifiers are
      also useful as they enable longitudinal monitoring of brain function.

PMID- 25596196
TI  - Establishment of a prospective cohort of mechanically ventilated patients in five
      intensive care units in Lima, Peru: protocol and organisational characteristics
      of participating centres.
AB  - INTRODUCTION: Mechanical ventilation is a cornerstone in the management of
      critically ill patients worldwide; however, less is known about the clinical
      management of mechanically ventilated patients in low and middle income countries
      where limitation of resources including equipment, staff and access to medical
      information may play an important role in defining patient-centred outcomes. We
      present the design of a prospective, longitudinal study of mechanically
      ventilated patients in Peru that aims to describe a large cohort of mechanically
      ventilated patients and identify practices that, if modified, could result in
      improved patient-centred outcomes and lower costs. METHODS AND ANALYSIS: Five
      Peruvian intensive care units (ICUs) and the Medical ICU at the Johns Hopkins
      Hospital were selected for this study. Eligible patients were those who underwent
      at least 24 h of invasive mechanical ventilation within the first 48 h of
      admission into the ICU. Information on ventilator settings, clinical management
      and treatment were collected daily for up to 28 days or until the patient was
      discharged from the unit. Vital status was assessed at 90 days post enrolment. A
      subset of participants who survived until hospital discharge were asked to
      participate in an ancillary study to assess vital status, and physical and mental
      health at 6, 12, 24 and 60 months after hospitalisation, Primary outcomes include
      90-day mortality, time on mechanical ventilation, hospital and ICU lengths of
      stay, and prevalence of acute respiratory distress syndrome. In subsequent
      analyses, we aim to identify interventions and standardised care strategies that
      can be tailored to resource-limited settings and that result in improved patient
      centred outcomes and lower costs. ETHICS AND DISSEMINATION: We obtained ethics
      approval from each of the four participating hospitals in Lima, Peru, and at the
      Johns Hopkins School of Medicine, Baltimore, USA. Results will be disseminated as
      several separate publications in different international journals.

PMID- 25596197
TI  - The association between daily physical activity and plasma B-type natriuretic
      peptide in patients with glucose intolerance: a cross-sectional study.
AB  - OBJECTIVES: In spite of accumulating evidences suggesting an inverse association
      between insulin resistance and plasma B-type natriuretic peptide (BNP) levels,
      the effect of daily physical activity on plasma BNP in individuals with glucose
      intolerance remains unknown. We investigated the association of physical activity
      level (PAL) with plasma BNP in patients with impaired fasting glucose, impaired
      glucose tolerance and type 2 diabetes. DESIGN: Cross-sectional study. SETTING:
      Outpatients visiting the National Center for Global Health and Medicine Kohnodai
      Hospital. PARTICIPANTS: A total of 60 patients with glucose intolerance who did
      not take any hypoglycaemic agents, cholesterol-lowering agents and
      antihypertensive agents were recruited. Patients who were diagnosed as having
      heart failure and renal impairment, engaged in sports-like exercise and
      resistance training were excluded. PRIMARY OUTCOME MEASURES: PAL was objectively
      measured by a triaxial accelerometer. The association between PAL and plasma BNP
      levels was assessed by multiple regression analysis. RESULTS: PAL was positively
      correlated with plasma BNP levels (r=0.296, p=0.021). PAL was still significantly
      correlated with plasma BNP levels after adjustment for age (beta=0.290, p=0.014),
      and adjustment for age and body mass index (beta=0.282, p=0.018). Plasma BNP
      levels were inversely correlated with serum insulin levels (r=-0.350, p=0.006)
      and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r=-0.363,
      p=0.004). Serum insulin levels (mean+/-SD, 8.1+/-6.4 MUU/mL) and HOMA-IR (2.4+/
      1.9) in the high-BNP group were significantly lower than those (11.2+/-7.4 MUU/mL
      and 3.7+/-3.0, respectively) in the low-BNP group. CONCLUSIONS: Our findings
      propose the possibility that plasma BNP may be increased by daily physical
      activity and BNP is associated with insulin resistance.

PMID- 25596198
TI  - The efficacy of activated protein C for the treatment of sepsis: incorporating
      observational evidence with a Bayesian approach.
AB  - OBJECTIVE: The present study aimed to combine observational evidence with
      randomised controlled trials (RCTs) by using the Bayesian approach. DATA SOURCES:
      Electronic databases, including PubMed, Cochrane Central Register of Controlled
      Trials (CENTRAL), ISI Web of Science, EMBASE and EBSCO were searched from
      inception to January 2014. STUDY ELIGIBILITY: RCTs and observational studies (OS)
      investigating the effectiveness of activated protein C (aPC) on mortality
      reduction were included for analysis. PARTICIPANTS: Patients with sepsis.
      INTERVENTION: aPC. SYNTHESIS METHODS: Observational evidence was incorporated
      into the analysis by using power transformed priors in a Bayesian. Trial
      sequential analysis was performed to examine changes over time and whether
      further studies need to be conducted. MAIN RESULTS: a total of 7 RCTs and 12 OS
      were included for the analysis. There was moderate heterogeneity among included
      RCTs (I(2)=48.6%, p=0.07). The pooled OR for mortality from RCTs was 1.00 (95% CI
      0.84 to 1.19). In OS, there was potential publication bias as indicated by the
      funnel plot and the pooled OR for mortality with the use of aPC was 0.67 (95% CI
      0.62 to 0.72). The pooled effect sizes of RCTs were changed by using different
      power transform priors derived from observational evidence. When observational
      evidence was used at its 'face value', the treatment effect of aPC was
      statistically significant in reducing mortality. CONCLUSIONS: while RCT evidence
      showed no beneficial effect of aPC on sepsis, observational evidence showed a
      significant treatment effect of aPC. By using power transform priors in Bayesian
      model, we explicitly demonstrated how RCT evidence could be changed by
      observational evidence. TRIAL REGISTRATION NUMBER: The protocol for the current
      study was registered in PROSPERO (registration number: CRD42014009562).

PMID- 25596200
TI  - Differentiation between mycoplasma and viral community-acquired pneumonia in
      children with lobe or multi foci infiltration: a retrospective case study.
AB  - OBJECTIVES: To analyse the clinical features, inflammatory markers and
      radiographs of community-acquired pneumonia (CAP) cases with lobe or multi foci
      infiltration; with a special focus on factors which allow the differential
      diagnosis of viral and mycoplasma pneumonia. SETTING: Retrospective chart review
      of CAP cases in a large university teaching hospital. PARTICIPANTS: 126
      paediatric CAP cases, with lobe or multi foci infiltration, presenting between
      May 2012 and April 2013. Demographic data, clinical presentation on admission or
      referral, laboratory tests, prior history, and radiography were collected for
      each case if available. PRIMARY AND SECONDARY OUTCOME MEASURES: We used
      univariate and multivariate logistic regression to determine the significant
      factors which allow the differential diagnosis of viral and mycoplasma CAP with
      lobe or multi foci infiltration. RESULTS: There were 71 (56%) male and 55 (44%)
      female CAP cases with lobar or multi foci infiltration. 70 pneumonia cases were
      caused by Mycoplasma pneumoniae and 18 by viruses. Univariate analysis of the
      mycoplasma and viral causes of the CAP revealed that increased respiratory rate,
      wheeze, male gender and lymphocyte percentage were the factors associated with
      the differentiation of mycoplasma and viral aetiologies of pneumonia (p<0.05). A
      stepwise logistic regression analysis was performed to assess independent factors
      which allow the differential diagnosis of viral and mycoplasma pneumonia.
      Increased respiratory rate, wheeze, and lymphocyte percentage were reliable
      independent factors which allow the differential diagnosis of viral and
      mycoplasma CAP with lobar or multi foci infiltration. CONCLUSIONS: Whether the
      CAP with lobar or multi foci infiltration was caused by mycoplasma species or
      viruses could not be inferred from the radiological patterns. Wheeze, lymphocyte
      percentage and respiratory rate were independent factors which allowed the
      differential diagnosis of viral and mycoplasma CAP with lobar or multi foci
      infiltration.

PMID- 25596199
TI  - Detection for pathway effect contributing to disease in systems epidemiology with
      a case-control design.
AB  - OBJECTIVES: Identification of pathway effects responsible for specific diseases
      has been one of the essential tasks in systems epidemiology. Despite some advance
      in procedures for distinguishing specific pathway (or network) topology between
      different disease status, statistical inference at a population level remains
      unsolved and further development is still needed. To identify the specific
      pathways contributing to diseases, we attempt to develop powerful statistics
      which can capture the complex relationship among risk factors. SETTING AND
      PARTICIPANTS: Acute myeloid leukaemia (AML) data obtained from 133 adults (98
      patients and 35 controls; 47% female). RESULTS: Simulation studies indicated that
      the proposed Pathway Effect Measures (PEM) were stable; bootstrap-based methods
      outperformed the others, with bias-corrected bootstrap CI method having the
      highest power. Application to real data of AML successfully identified the
      specific pathway (Treg->TGFbeta->Th17) effect contributing to AML with p values
      less than 0.05 under various methods and the bias-corrected bootstrap CI (-0.214
      to -0.020). It demonstrated that Th17-Treg correlation balance was impaired in
      patients with AML, suggesting that Th17-Treg imbalance potentially plays a role
      in the pathogenesis of AML. CONCLUSIONS: The proposed bootstrap-based PEM are
      valid and powerful for detecting the specific pathway effect contributing to
      disease, thus potentially providing new insight into the underlying mechanisms
      and ways to study the disease effects of specific pathways more comprehensively.

PMID- 25596201
TI  - The impact of a streamlined funding application process on application time: two
      cross-sectional surveys of Australian researchers.
AB  - OBJECTIVE: To examine if streamlining a medical research funding application
      process saved time for applicants. DESIGN: Cross-sectional surveys before and
      after the streamlining. SETTING: The National Health and Medical Research Council
      (NHMRC) of Australia. PARTICIPANTS: Researchers who submitted one or more NHMRC
      Project Grant applications in 2012 or 2014. MAIN OUTCOME MEASURES: Average
      researcher time spent preparing an application and the total time for all
      applications in working days. RESULTS: The average time per application increased
      from 34 working days before streamlining (95% CI 33 to 35) to 38 working days
      after streamlining (95% CI 37 to 39; mean difference 4 days, bootstrap p value
      <0.001). The estimated total time spent by all researchers on applications after
      streamlining was 614 working years, a 67-year increase from before streamlining.
      CONCLUSIONS: Streamlined applications were shorter but took longer to prepare on
      average. Researchers may be allocating a fixed amount of time to preparing
      funding applications based on their expected return, or may be increasing their
      time in response to increased competition. Many potentially productive years of
      researcher time are still being lost to preparing failed applications.

PMID- 25596203
TI  - Surgical treatment of a mitral-aortic intervalvular fibrosa pseudoaneurysm.

PMID- 25596202
TI  - Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in
      high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled
      trial.
AB  - INTRODUCTION: Otitis media (OM) starts within weeks of birth in almost all
      Indigenous infants living in remote areas of the Northern Territory (NT). OM and
      associated hearing loss persist from infancy throughout childhood and often into
      adulthood. Educational and social opportunities are greatly compromised.
      Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM
      pathogens that densely colonise the nasopharynx and infect the middle ear from
      very early in life. Our hypothesis is that compared to current single vaccine
      schedules, a combination of vaccines starting at 1 month of age, may provide
      earlier, broadened protection. METHODS AND ANALYSES: This randomised outcome
      assessor, blinded controlled trial will recruit 425 infants between 28 and 38
      days of age and randomly allocate them (1:1:1) to one of three pneumococcal
      conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13
      at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2
      and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at
      7 months of age are immunogenicity of specific vaccine antigens (geometric mean
      concentration (GMC) and proportion of participants with above threshold GMC of
      0.35 ug/L). Secondary outcomes at all timepoints are additional immunogenicity
      measures and proportion of participants with nasopharyngeal carriage of vaccine
      type pneumococci and NTHi, and any OM, including any tympanic membrane
      perforation. Parental interviews will provide data on common risk factors for OM.
      ETHICS AND DISSEMINATION: Ethical approval has been obtained from NT Department
      of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West
      Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial
      results, data analyses, interpretation and conclusions will be presented in
      appropriate written and oral formats to parents and guardians, participating
      communities, local, national and international conferences, and published in peer
      reviewed open access journals. TRIAL REGISTRATION NUMBERS: ACTRN12610000544077
      and NCT01174849.

PMID- 25596204
TI  - Large mobile atheromatous plaque of the ascending aorta.

PMID- 25596205
TI  - scrm: efficiently simulating long sequences using the approximated coalescent
      with recombination.
AB  - MOTIVATION: Coalescent-based simulation software for genomic sequences allows the
      efficient in silico generation of short- and medium-sized genetic sequences.
      However, the simulation of genome-size datasets as produced by next-generation
      sequencing is currently only possible using fairly crude approximations. RESULTS:
      We present the sequential coalescent with recombination model (SCRM), a new
      method that efficiently and accurately approximates the coalescent with
      recombination, closing the gap between current approximations and the exact
      model. We present an efficient implementation and show that it can simulate
      genomic-scale datasets with an essentially correct linkage structure.

PMID- 25596206
TI  - Mutuelles de sante en Afrique : caracteristiques et relations contractuelles avec
      les prestataires de soins pour la prise en charge de la qualite des soins.
AB  - En Afrique, une part importante de la population est encore confrontee a
      plusieurs barrieres pour acceder aux soins. Les mutuelles de sante (MS) sont
      mises en place pour reduire la barriere financiere et assurer a leurs membres un
      acces a des soins de qualite. Les MS etablissent des relations avec les
      prestataires de soins sous forme de contrat, dont certaines clauses peuvent
      contenir des notions de qualite des soins (QS). A travers une vue d'ensemble de
      la typologie de 180 MS de 14 pays (dans Afrique Ouest et Centrale), cet article
      vise a analyser dans quelle mesure les caracteristiques des MS influencent la
      mise en oeuvre de mecanismes contractuels susceptibles de faciliter la discussion
      sur la QS. L'hypothese de cette association a ete etudiee avec trois types de
      caracteristiques (taille, utilisation des services et volume des soins achetes)
      et huit variables relatives a la contractualisation et la QS (existence d'un
      contrat, organisation de rencontres, frequence de ces rencontres, presence de
      notions de QS dans le contrat, negociation du contrat, revision du contrat,
      revision des clauses specifiques a la QS et organisation de rencontres pour
      discuter de QS). Les MS de type communautaire representent 80% des mutuelles
      etudiees (60% d'entre elles sont localisees en zone rurale). Les MS
      professionnelles representent 17% et se concentrent principalement au Mali et en
      Cote d'Ivoire. La quasi-totalite des MS disposent de contrats ecrits et contenant
      des notions relatives a la QS. Bien que les MS de grande taille ayant des
      resultats financiers importants negocient plus les aspects lies a la qualite des
      soins lors de l'elaboration de la convention, les MS de taille et aux
      performances financieres plus modestes mettent en oeuvre des mecanismes plus
      reguliers de concertation avec les prestataires. Ces rencontres sont susceptibles
      de creer un espace de prise en charge de la QS.

PMID- 25596207
TI  - Pathomechanisms of atrophy in insular cortex in Alzheimer's disease.
AB  - The insular cortex is associated with neuropsychiatric symptoms, changes in
      cardiovascular and autonomic control, and mortality in Alzheimer's dementia.
      However, the insular cortex does not provide information on the contribution of
      the other cortices to cognitive decline. We hypothesized that the factors that
      affect to atrophy in insular cortex are different from other cortical regions. A
      total of 42 patients with probable Alzheimer's dementia were included in the
      analyses. The manual drawing of regions of interest was used to detect insular
      cortex located in the deep gray matter and to avoid coatrophy. Covariates, which
      could affect to the atrophy of the cerebral cortex, were selected based on
      previous studies. Any of the demographic factors, vascular risk factors, and the
      severity scales of dementia was not associated with any insular volume ratio. We
      suggest that the pathomechanisms of atrophy in insular cortex are different from
      those of other cortex regions in Alzheimer's disease. 

PMID- 25596209
TI  - Vitamin E in New-Generation Lipid Emulsions Protects Against Parenteral Nutrition
      Associated Liver Disease in Parenteral Nutrition-Fed Preterm Pigs.
AB  - INTRODUCTION: Parenteral nutrition (PN) in preterm infants leads to PN-associated
      liver disease (PNALD). PNALD has been linked to serum accumulation of
      phytosterols that are abundant in plant oil but absent in fish oil emulsions.
      HYPOTHESIS: Whether modifying the phytosterol and vitamin E composition of soy
      and fish oil lipid emulsions affects development of PNALD in preterm pigs.
      METHODS: We measured markers of PNALD in preterm pigs that received 14 days of PN
      that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2)
      Intralipid + vitamin E (ILE, d-alpha-tocopherol), (3) Omegaven (OV, 100% fish
      oil), or (4) Omegaven + phytosterols (PS, beta-sitosterol, campesterol, and
      stigmasterol). RESULTS: Serum levels of direct bilirubin, gamma glutamyl
      transferase, serum triglyceride, low-density lipoprotein, and hepatic
      triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS
      compared to IL. Hepatic cholesterol 7-hydroxylase and organic solute transporter
      alpha expression was lower (P < .05) and portal plasma FGF19 higher in the ILE,
      OV, and PS vs IL. Hepatic expression of mitochondrial carnitine
      palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation
      genes was higher in ILE, OV, and PS vs IL. In vivo (13)C-CDCA clearance and
      expression of pregnane X receptor target genes, cytochrome P450 3A29 and
      multidrug resistance-associated protein 2, were higher in ILE, OV, and PS vs IL.
      CONCLUSIONS: alpha-tocopherol in Omegaven and added to Intralipid prevented serum
      and liver increases in biliary and lipidemic markers of PNALD in preterm piglets.
      The addition of phytosterols to Omegaven did not produce evidence of PNALD.

PMID- 25596210
TI  - A Descriptive Study of the Risk Factors Associated With Catheter-Related
      Bloodstream Infections in the Home Parenteral Nutrition Population.
AB  - BACKGROUND: Home parenteral nutrition (HPN) is increasingly used for nutrition
      support after patients are discharged from the hospital. Catheter-related
      bloodstream infections (CR-BSI) are a common and potentially fatal complication
      of HPN. The risk factors for development of CR-BSI in the outpatient setting are
      poorly understood. METHODS: We conducted an observational, retrospective study of
      225 patients discharged from Barnes-Jewish Hospital on HPN between January 1,
      2007, and December 31, 2009. HPN complications were defined as any cause that led
      to either premature discontinuation of HPN therapy or catheter replacement. CR
      BSI events were identified by provider documentation. We calculated the overall
      complication rate and the complication rate specifically due to CR-BSI. Backward
      stepwise Cox regression analyses were used to assess for independent predictors
      of catheter-related complications. RESULTS: In total, 111 of 225 patients (49%)
      developed complications while receiving HPN (incidence = 5.06 episodes/1000
      catheter days). Sixty-eight of 225 patients (30%) required catheter removal for
      CR-BSI (incidence = 3.10 episodes/1000 catheter days). Independent predictors of
      line removal specifically due to infection included anticoagulant use, ulcer or
      open wound, and Medicare or Medicaid insurance. The following risk factors were
      associated with catheter-associated complications and/or CR-BSI: the presence of
      ulcers, the use of systemic anticoagulants, public insurance (Medicare or
      Medicaid), and patient age. Independent predictors of line removal for any
      complication included age and anticoagulant use. CONCLUSION: Catheter-related
      complications were extremely common in patients receiving HPN. Healthcare
      providers caring for individuals who require HPN should be aware of risk factors
      for complications.

PMID- 25596211
TI  - Does screening for disease save lives in asymptomatic adults? Systematic review
      of meta-analyses and randomized trials.
AB  - BACKGROUND: Several popular screening tests, such as mammography and prostate
      specific antigen, have met with wide controversy and/or have lost their
      endorsement recently. We systematically evaluated evidence from randomized
      controlled trials (RCTs) as to whether screening decreases mortality from
      diseases where death is a common outcome. METHODS: We searched three sources:
      United States Preventive Services Task Force (USPSTF), Cochrane Database of
      Systematic Reviews, and PubMed. We extracted recommendation status, category of
      evidence and RCT availability on mortality for screening tests for diseases on
      asymptomatic adults (excluding pregnant women and children) from USPSTF. We
      identified meta-analyses and individual RCTs on screening and mortality from
      Cochrane and PubMed. RESULTS: We selected 19 diseases (39 tests) out of 50
      diseases/disorders for which USPSTF provides screening evaluation. Screening is
      recommended for 6 diseases (12 tests) out of the 19. We assessed 9 non
      overlapping meta-analyses and 48 individual trials for these 19 diseases. Among
      the results of the meta-analyses, reductions where the 95% confidence intervals
      (CIs) excluded the null occurred for four disease-specific mortality estimates
      (ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer;
      fecal occult blood test and flexible sigmoidoscopy for colorectal cancer) and for
      none of the all-cause mortality estimates. Among individual RCTs, reductions in
      disease-specific and all-cause mortality where the 95% CIs excluded the null
      occurred in 30% and 11% of the estimates, respectively. CONCLUSIONS: Among
      currently available screening tests for diseases where death is a common outcome,
      reductions in disease-specific mortality are uncommon and reductions in all-cause
      mortality are very rare or non-existent.

PMID- 25596212
TI  - Commentary: Tempering expectations of screening: what is the most authoritative
      advice we can give, given the data that we have?

PMID- 25596214
TI  - Commentary on N Saquib et al. Does screening for disease save lives in
      asymptomatic adults? Systematic review of 5 meta-analyses and randomized trials.

PMID- 25596213
TI  - Commentary: Screening: a seductive paradigm that has generally failed us.

PMID- 25596215
TI  - Ultrasound-guided popliteal sciatic nerve block using a pocket-sized ultrasound
      machine: preliminary evidence.

PMID- 25596216
TI  - Ultrasound standard for obturator nerve block: the modified Taha's approach.

PMID- 25596217
TI  - High-dose tranexamic acid for treating postpartum haemorrhage after vaginal
      delivery.

PMID- 25596218
TI  - Comparison of transversus abdominis plane block and epidural analgesia for pain
      relief after surgery.

PMID- 25596219
TI  - Problematic comparisons.

PMID- 25596220
TI  - Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and
      Ringer's lactate: Reply to Prof Priebe.

PMID- 25596221
TI  - Depth of anaesthesia optimisation and postoperative cognitive dysfunction.

PMID- 25596222
TI  - Neurotoxicity of general anaesthesia is hypothetical.

PMID- 25596223
TI  - Immediate postoperative pain can also be predicted by pupillary pain index in
      children.

PMID- 25596224
TI  - Predictability of stroke volume variation.

PMID- 25596225
TI  - Use of analgesia monitors to optimize the management of immediate postoperative
      pain.

PMID- 25596226
TI  - Monitor stroke volume and heart rate.

PMID- 25596227
TI  - Posture at laryngoscopy.

PMID- 25596228
TI  - Dynamic optimization of height relation between anaesthetist's chest and
      patient's face during tracheal intubation.

PMID- 25596229
TI  - Teamwork in anaesthetics and critical care is possible.

PMID- 25596231
TI  - Re: Improving teamwork in anaesthesia and critical care: perhaps there really is
      no 'I' in ICU.

PMID- 25596230
TI  - Improving teamwork in anaesthesia and critical care: practical lessons to learn.

PMID- 25596232
TI  - Reply from the author.

PMID- 25596233
TI  - Bone cement embolism attached to central venous catheter.

PMID- 25596240
TI  - Clinical utility of lactate dehydrogenase: a historical perspective.

PMID- 25596241
TI  - Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology
      and the risk of cervical precancer: results from the CLEAR HPV study.
AB  - OBJECTIVES: The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay
      (AHPV-GT) is a qualitative E6/ E7 oncogene messenger RNA test that detects HPV 16
      and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study
      was the pivotal, prospective, multicenter US clinical study to validate the
      Aptima HPV (AHPV) assays. METHODS: In this analysis, we evaluated the clinical
      performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial
      neoplasia grade 2 or more severe (CIN2 +) and grade 3 (CIN3) or adenocarcinoma in
      situ in 912 women with atypical squamous cells of undetermined significance (ASC
      US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV)
      positives as determined by the AHPV assay. RESULTS: Overall, the percent positive
      for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among
      hrHPV-positive women, the risks of CIN2 + were 37.0% for HPV 16 positives, 15.9%
      for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV
      negatives. The risks of CIN3 + were 20.5% for HPV 16 positives, 9.1% for HPV
      18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives.
      CONCLUSIONS: We demonstrated that AHPV-GT is a reliable and effective test for
      cervical cancer risk stratification in women with an ASC-US cytology diagnosis.

PMID- 25596242
TI  - Automatic recognition of atypical lymphoid cells from peripheral blood by digital
      image analysis.
AB  - OBJECTIVES: The objective was the development of a method for the automatic
      recognition of different types of atypical lymphoid cells. METHODS: In the method
      development, a training set (TS) of 1,500 lymphoid cell images from peripheral
      blood was used. To segment the images, we used clustering of color components and
      watershed transformation. In total, 113 features were extracted for lymphocyte
      recognition by linear discriminant analysis (LDA) with a 10-fold cross-validation
      over the TS. Then, a new validation set (VS) of 150 images was used, performing
      two steps: (1) tuning the LDA classifier using the TS and (2) classifying the VS
      in the different lymphoid cell types. RESULTS: The segmentation algorithm was
      very effective in separating the cytoplasm, nucleus, and peripheral zone around
      the cell. From them, descriptive features were extracted and used to recognize
      the different lymphoid cells. The accuracy for the classification in the TS was
      98.07%. The precision, sensitivity, and specificity values were above 99.7%,
      97.5%, and 98.6%, respectively. The accuracy of the classification in the VS was
      85.33%. CONCLUSIONS: The method reaches a high precision in the recognition of
      five different types of lymphoid cells and could allow for the design of a
      diagnosis support tool in the future.

PMID- 25596243
TI  - The vascular marker CD31 also highlights histiocytes and histiocyte-like cells
      within cutaneous tumors.
AB  - OBJECTIVES: While useful in diagnosing angiosarcomas, CD31 can also highlight
      histiocytes within soft tissue tumors and lead to errors in diagnosis. We sought
      to determine how often CD31 highlights cutaneous histiocytomas and histiocytoma
      mimics. METHODS: We examined eight epithelioid cell histiocytomas (ECHs), 12
      xanthogranulomas (XGs), nine cases of Langerhans cell histiocytosis (LCH), eight
      reticulohistiocytomas, 11 xanthomas, 29 atypical fibroxanthomas, nine granular
      cell tumors, four cases of angiolymphoid hyperplasia with eosinophilia, nine
      intradermal Spitz nevi, and nine angiosarcomas with antibodies directed against
      CD31, CD34, CD163, and factor VIII. RESULTS: CD31 marked cells in three of 12
      XGs, four of nine cases of LCH, one of eight reticulohistiocytomas, one of 11
      xanthomas, 10 of 29 atypical fibroxanthomas, four of four cases of angiolymphoid
      hyperplasia with eosinophilia, nine of nine angiosarcomas, zero of nine granular
      cell tumors, and zero of eight ECHs. CD34 and factor VIII were negative in all
      nonvascular cases. CONCLUSIONS: Our results indicate that CD31 can mark lesional
      cells and imitate vascular tumors in cutaneous histiocytomas and histiocytoma
      mimics, an error that can be avoided by using a panel of antibodies.

PMID- 25596244
TI  - Detection of acetylcholine receptor modulating antibodies by flow cytometry.
AB  - OBJECTIVES: To determine the clinical utility and performance characteristics of
      a laboratory-adapted flow cytometric method for the detection of acetylcholine
      receptor (AChR) modulating antibodies in myasthenia gravis (MG). METHODS: Serum
      samples from 120 healthy donors and 100 patients with suspected MG were assessed
      for the ability to reduce surface AChR concentrations (antigenic modulation) in
      RD (TE671) or DB40 human muscle cell lines by flow cytometry. Reference ranges
      were established by receiver operating characteristic curve analysis, and results
      were then compared with those of the current radioimmunoassay (RIA). RESULTS:
      Flow cytometric results from the RD cell line had an interpretive threshold of
      46% modulation or greater and correlated best (98% sensitivity, 99% specificity)
      with those of the current RIA. CONCLUSIONS: The new flow cytometric method using
      the RD cell platform provided higher quality clinical results, a more robust and
      efficient assay format, a significant cost savings, and less environmental
      burden.

PMID- 25596245
TI  - Adequacy of core needle biopsy specimens and fine-needle aspirates for molecular
      testing of lung adenocarcinomas.
AB  - OBJECTIVES: Molecular testing of lung adenocarcinomas for epidermal growth factor
      (EGFR) mutations and an anaplastic lymphoma kinase (ALK) translocation is
      important to guide directed therapy with tyrosine kinase inhibitors. The goal of
      this study was to determine whether transthoracic computed tomography-guided core
      needle biopsy (CNB) and fine-needle aspiration (FNA) biopsy specimens were
      equally suitable for molecular testing. METHODS: We determined the percentage of
      52 CNB and 120 FNA specimens that contained sufficient paraffin-embedded tumor
      tissue for EGFR, KRAS, and ALK testing over a period of 2 years. We correlated
      sample sufficiency with the sampling method, tumor size, biopsy operator,
      pathologist assessing the adequacy of the sample, and the number of FNA passes
      performed. RESULTS: Univariate analysis showed that CNB specimens provided a
      significantly higher number of samples sufficient for molecular testing than did
      FNA specimens (67% vs 46%; P = .007) and that one operator achieved a
      significantly higher percentage of sufficient FNA specimens. Binomial logistic
      regression found sufficiency of FNA samples to correlate with tumor size (P =
      .015) but not operator. CONCLUSIONS: When paraffin-embedded tissue is used for
      molecular testing of lung cancer, CNB specimens are more likely than FNA
      specimens to provide adequate tissue for molecular testing. Obtaining a
      sufficient FNA specimen depends on the tumor size and the individual performing
      the biopsy.

PMID- 25596246
TI  - Bone marrow necrosis: ten-year retrospective review of bone marrow biopsy
      specimens.
AB  - OBJECTIVES: Bone marrow can undergo necrosis for many different causes; malignant
      causes are reported to be more frequent. METHODS: We undertook a 10-year
      retrospective review of all bone marrow biopsy specimens with bone marrow
      necrosis at our institution. RESULTS: Identified cases represented approximately
      0.3% of our bone marrow cases. Most identified bone marrow cases with necrosis
      were involved by metastatic tumor or hematolymphoid malignancy (90% of total) in
      relatively equal proportions. In those cases of bone marrow necrosis with
      hematolymphoid malignancy, lymphoid disease predominated and the necrosis was
      often seen in the setting of chemotherapy. In metastatic tumor cases, necrosis
      seemed to enrich in prostate adenocarcinoma and Ewing sarcoma/primitive
      neuroectodermal tumor; neuroblastoma showed much less necrosis. Ten percent of
      patients with bone marrow necrosis had no underlying malignancy, and the
      associated causes varied. CONCLUSIONS: The causes of bone marrow necrosis are
      diverse but should always prompt careful assessment for malignancy and infectious
      etiology.

PMID- 25596247
TI  - Flow cytometric analysis of lymphoid enhancer-binding factor 1 in diagnosis of
      chronic lymphocytic leukemia/small lymphocytic lymphoma.
AB  - OBJECTIVES: Nuclear overexpression of lymphoid enhancer-binding factor 1 (LEF1)
      assessed by immunohistochemistry has been shown to be highly associated with
      chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) among small B
      cell lymphomas. The purpose of this study was to evaluate the utility of flow
      cytometric analysis of LEF1 in the diagnosis of CLL/SLL. METHODS: Normal
      peripheral blood was used to validate the test. Flow cytometric analysis of LEF1
      was performed in 64 patient samples qualitatively and quantitatively by comparing
      the staining intensity and the ratios of the median fluorescence intensities
      (MFIs) of LEF1 in B cells of interest to the internal reference cell populations.
      The results were correlated with the pathologic diagnosis. RESULTS: Proper sample
      processing ensured sufficient separation of positive LEF1 staining in T cells
      from negative staining in normal B and natural killer (NK) cells. Qualitative
      analysis of patient samples showed that all 25 cases of CLL/SLL but none of the
      other small B-cell lymphomas were positive for LEF1. Using a B/NK MFI ratio of
      1.5 and B/T MFI ratio of 0.45 separated CLL/SLL cases from non-CLL lymphomas.
      CONCLUSIONS: Flow cytometric analysis of LEF1 is sufficient to differentiate
      CLL/SLL from other small B-cell lymphomas and may serve as a useful tool in the
      diagnosis of CLL/SLL.

PMID- 25596248
TI  - Thyroid carcinoma showing thymus-like elements: a clinicopathologic,
      immunohistochemical, ultrastructural, and molecular analysis.
AB  - OBJECTIVES: To investigate the clinicopathologic, immunophenotypic,
      ultrastructural, and molecular features of thyroid carcinoma showing thymus-like
      elements (CASTLE). METHODS: We retrospectively analyzed the clinicopathologic
      data of 10 patients with CASTLE and described the immunophenotypic and
      ultrastructural features of these tumors. The expression of Epstein-Barr virus
      encoded RNA and the gene status of EGFR, C-KIT, and HER-2 were also assessed by
      molecular techniques. RESULTS: The tumor cells were positive for CD5, CD117, p63,
      HMWK, EGFR, GLUT-1, Pax8, E-cadherin, bcl-2, and p53 in all cases and for CA-IX,
      CEA, p16, HER-2, and neuroendocrine markers in some cases. Ultrastructural
      examination indicated that the tumor cells contained large quantities of
      tonofilament with abundant intercellular desmosomes, including intracytoplasmic
      neuroendocrine granules in one case. EGFR gene amplification in two patients and
      polyploidy of chromosome 7 in one patient were identified by fluorescence in situ
      hybridization. Sequencing analysis revealed that a synonymous mutation, Q787Q
      2363 (G->A), occurred on exon 20 of the EGFR gene in three patients. CONCLUSIONS:
      GLUT-1 can be used as a novel biomarker for CASTLE, and combined detection of
      GLUT-1 with CD5 and CD117 aids in the diagnosis of this tumor. Aberrant
      expression of Bcl-2, p53, p16, E-cadherin, EGFR, C-KIT, and HER-2 may play
      important roles in the development of CASTLE.

PMID- 25596249
TI  - A hybrid approach to urine drug testing using high-resolution mass spectrometry
      and select immunoassays.
AB  - OBJECTIVES: The major objective of this research was to propose a simplified
      approach for the evaluation of medication adherence in chronic pain management
      patients, using liquid chromatography time-of-flight (TOF) mass spectrometry,
      performed in parallel with select homogeneous enzyme immunoassays (HEIAs). We
      called it a "hybrid" approach to urine drug testing. METHODS: The hybrid approach
      was defined based on anticipated positivity rates, availability of commercial
      reagents for HEIAs, and assay performance, particularly analytical sensitivity
      and specificity for drug(s) of interest. Subsequent to implementation of the
      hybrid approach, time to result was compared with that observed with other urine
      drug testing approaches. RESULTS: Opioids, benzodiazepines, zolpidem, amphetamine
      like stimulants, and methylphenidate metabolite were detected by TOF mass
      spectrometry to maximize specificity and sensitivity of these 37 drug analytes.
      Barbiturates, cannabinoid metabolite, carisoprodol, cocaine metabolite, ethyl
      glucuronide, methadone, phencyclidine, propoxyphene, and tramadol were detected
      by HEIAs that performed adequately and/or for which positivity rates were very
      low. Time to result was significantly reduced compared with the traditional
      approach. CONCLUSIONS: The hybrid approach to urine drug testing provides a
      simplified and analytically specific testing process that minimizes the need for
      secondary confirmation.

PMID- 25596250
TI  - Laboratory measurements of the oral direct factor Xa inhibitor edoxaban:
      comparison of prothrombin time, activated partial thromboplastin time, and
      thrombin generation assay.
AB  - OBJECTIVES: Edoxaban, an oral direct factor Xa inhibitor, does not require
      routine monitoring. However, assessment of the anticoagulant effects may be
      required in certain situations. METHODS: We investigated the effects of edoxaban
      on prothrombin time (PT), activated partial thromboplastin time (aPTT), and
      thrombin generation using human platelet-poor plasma (PPP) or platelet-rich
      plasma (PRP). RESULTS: Edoxaban concentration-dependently prolonged PT and aPTT.
      There was a considerable variation in the magnitude of PT prolongation among the
      reagents used. The variability in aPTT prolongation among the reagents was
      smaller than that of PT. Edoxaban concentration-dependently inhibited thrombin
      generation, with a more potent effect seen in PPP than in PRP. Thrombin
      generation assay was three times more sensitive to edoxaban than PT and aPTT.
      CONCLUSIONS: PT had disadvantages of a large variability among different PT
      reagents. aPTT could be used as a conventional and convenient test with a smaller
      variation among reagents. Thrombin generation was the most sensitive assay.

PMID- 25596251
TI  - Enhanced FHL2 and TGF-beta1 Expression Is Associated With Invasive Growth and
      Poor Survival in Malignant Melanomas.
AB  - OBJECTIVES: This study examines the expression and the role of four-and-a-half
      LIM domains protein 2 (FHL2) and transforming growth factor beta1 (TGF-beta1) in
      human malignant melanoma. It is determined whether both proteins influence
      melanoma survival time. METHODS: We analyzed the immunohistochemical staining
      intensities of FHL2 and TGF-beta1 in normal skin and in 50 malignant melanomas
      with different mutation status (BRAF-V600E, NRAS codon 61 mutation, and wild
      type). Survival data were available for 45 cases. RESULTS: In melanocytes of
      nonneoplastic human skin, FHL2 expression was absent. In contrast, 38 (76%) of 50
      melanomas showed strong cytoplasmic and partly nuclear FHL2 expression. At the
      invasion front, cytoplasmic TGF-beta1 staining was observed in 32 (64%) of 50
      melanomas, and a correlation of FHL2 and TGF-beta1 staining intensities was
      detectable. In follow-up analyses, enhanced FHL2 and TGF-beta1 staining
      intensities in the tumor invasion front were associated with poor survival.
      CONCLUSIONS: Enhanced FHL2 and TGF-beta1 expression is correlated with poor
      survival in human malignant melanoma. Protumorigenic effects of autocrine TGF
      beta1 secretion might be exerted by induction of FHL2 expression in melanoma
      cells. Since melanomas treated with targeted therapies often do not show
      sufficient response rates, inhibition of FHL2 and/or TGF-beta1 might be a
      promising therapeutic approach.

PMID- 25596253
TI  - Subcutaneous panniculitis-like T-cell lymphoma with bone marrow involvement.
AB  - OBJECTIVES: To describe a rare case of subcutaneous panniculitis-like T-cell
      lymphoma (SPTCL) with morphologic and immunophenotypic evidence of bone marrow
      involvement. METHODS: Biopsy specimens of skin and subcutis and bone marrow were
      examined using H&E-stained sections. Immunohistochemical studies for CD2, CD3,
      CD4, CD5, CD7, CD8, CD20, CD30, CD56, and granzyme B were reviewed. In addition,
      T-cell receptor gamma gene rearrangement studies were performed. RESULTS: A bone
      marrow core biopsy demonstrated several lymphohistiocytic aggregates containing
      atypical, cytotoxic T cells that rimmed adipocytes and were associated with
      karyorrhexis. These T cells were morphologically and immunophenotypically
      identical to a concurrent SPTCL, expressing CD2, CD3, CD7, CD8, and granzyme B
      but with diminished CD5 expression. CONCLUSIONS: SPTCL may rarely involve the
      bone marrow. Bone marrow infiltrates show a similar morphologic and
      immunophenotypic appearance to those in the subcutaneous fibroadipose tissue,
      including rimming of adipocytes by neoplastic lymphocytes.

PMID- 25596252
TI  - Pathologic diagnostics of HER2 positivity in gastroesophageal adenocarcinoma.
AB  - OBJECTIVES: The human epidermal growth factor receptor 2 (HER2) oncogene shows
      overexpression in 15% to 30% of gastroesophageal adenocarcinomas. Targeted anti
      HER2 therapy with trastuzumab has been recently validated in advanced gastric and
      gastroesophageal junction cancer treatment. A standardized modified scoring
      system was recently introduced for gastroesophageal HER2 scoring. We aimed to
      validate this scoring system, including an analysis of interobserver variability
      of immunohistochemistry (IHC) scoring. METHODS: In total, 323 patients with
      histologically confirmed invasive gastric or esophageal adenocarcinoma were
      examined for HER2 by IHC and chromogenic in situ hybridization (CISH). IHC 3 + or
      IHC 2 +/CISH positive tumors were considered HER2 positive. Interobserver
      variability on IHC scoring using the currently standard modified HER2 scoring
      system was determined among three clinical pathologists. Clinicopathologic
      characteristics were retrospectively retrieved from the patient records. RESULTS:
      HER2 positivity was found in 50 (15.5%) of 323 patients. Interobserver agreement
      on IHC scoring was high (kappa = 0.78). Most disagreement was found in diffuse or
      mixed tumor types and in weak to moderate stained samples (IHC 2 +). The HER2 IHC
      scoring system is sensitive in differentiating HER2 status before ISH.
      CONCLUSIONS: The currently used standardized HER2 scoring system is an excellent,
      clinically applicable method to establish HER2 status in appropriately educated
      and trained pathologists.

PMID- 25596254
TI  - Multifocal mantle cell lymphoma in situ in the setting of a composite lymphoma.
AB  - OBJECTIVES: Mantle cell lymphoma in situ (MCLIS) consists of immunophenotypically
      defined but histologically inapparent neoplastic cells restricted to narrow
      mantle zones, without expansion or invasion beyond the mantle zone. We report a
      unique case of MCLIS associated with a much more manifest nodal marginal zone
      lymphoma (MZL) in an inguinal lymph node, porta hepatis lymph node, and bone
      marrow. METHODS: Biopsies from all three locations were evaluated using standard
      H&E-stained sections, immunohistochemistry, flow cytometry, metaphase
      cytogenetics, and/or fluorescence in situ hybridization (FISH). RESULTS: This
      case is unique for three reasons. First, the histologically covert mantle cell
      lymphoma was multifocal, detected in all three locations using one or more of
      flow cytometry, immunohistochemistry, cytogenetics, and FISH. Second, the MCLIS
      was always accompanied by a more histologically dominant MZL. Third, where
      evaluable, it did not grow in an appreciable mantle zone distribution, presumably
      due to destruction of the normal nodal architecture by the neoplastic MZL cells
      and the resulting absence of recognizable follicles and mantle zones.
      CONCLUSIONS: This unique case provides new insight into the pathogenesis of
      MCLIS.

PMID- 25596255
TI  - Solid pseudopapillary neoplasm collides with a well-differentiated pancreatic
      endocrine neoplasm in an adult man: case report and review of histogenesis.
AB  - OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare,
      clinicopathologically distinct neoplasm with a tendency to affect young women.
      The histogenesis of SPN is not well defined. Pancreatic endocrine neoplasms
      (PENs) are also uncommon tumors of the pancreas. METHODS: Our comprehensive
      review of the literature did not yield any reported cases of collision tumors of
      the above two neoplasms. We report a case of such a collision tumor in a 45-year
      old man. RESULTS: This tumor was an incidental finding on computed tomography,
      followed by fine-needle aspiration confirmation of a tumor that was initially
      diagnosed as an SPN only. A histologic examination of a 2.1-cm mass following
      distal pancreatectomy revealed a 0.7-cm PEN partly engulfed by an SPN. The tumors
      showed different morphologic and immunohistochemical features, confirming the
      presence of a collision tumor. CONCLUSIONS: A comparative analysis of
      immunoprofiles of these tumors yielded interesting findings, enabling us to
      postulate that SPNs may originate from a multipotential primordial cell that may
      follow different differentiation pathways, such as endocrine, epithelial, and
      acinar. The ultrastructures and immunophenotypic characteristics appear to
      support this hypothesis.

PMID- 25596256
TI  - Cyclin D1-positive diffuse large B-cell lymphoma with IGH-CCND1 translocation and
      BCL6 rearrangement: a report of two cases.
AB  - OBJECTIVES: To demonstrate and confirm the existence of cyclin D1-positive
      diffuse large B-cell lymphoma (DLBCL) with IGH-CCND1 rearrangement and discuss
      the rationale of differentiating this entity from blastoid and pleomorphic
      variants of mantle cell lymphoma (MCL). METHODS: Two cyclin D1-positive lymphomas
      with morphologic features of DLBCL and IGH-CCND1 translocations were
      characterized with respect to clinical features, as well as morphologic,
      immunophenotypic, cytogenetic, and molecular findings. RESULTS: The large tumor
      cells were CD20+, CD5-, CD10-, BCL6+, MUM1+, and cyclin D1+ in both cases. SOX11
      was negative. Epstein-Barr virus-encoded RNA in situ hybridization demonstrated
      diffuse positivity in case 1. BCL6 and IGH-CCND1 rearrangements were identified
      by fluorescence in situ hybridization in both cases. Specifically, the diagnosis
      of a relapsed DLBCL with acquisition of IGH-CCND1 was rendered for case 1,
      molecularly confirmed by the detection of identical monoclonal IGH rearrangements
      between the initial diagnostic DLBCL and relapse lymphoma. CONCLUSIONS: Our study
      demonstrates convincingly that IGH-CCND1 rearrangement leading to cyclin D1
      overexpression can occur in DLBCL and pose a potential diagnostic pitfall,
      requiring thorough knowledge of the clinicopathologic findings to allow accurate
      discrimination from a blastoid or pleomorphic MCL. The coexistence of IGH-CCND1
      and IGH-BCL6 rearrangements suggest that BCL6 and cyclin D1 may cooperate in the
      pathogenesis of DLBCL.

PMID- 25596257
TI  - A challenging diagnosis: crystal-storing histiocytosis in plasma cell myeloma.
AB  - OBJECTIVES: Crystal-storing histiocytosis (CSH) is an uncommon finding in plasma
      cell neoplasms. CSH is thought to be an intralysosomal deposition of secreted
      paraproteins or immunoglobulins, which usually express kappa immunoglobulin light
      chains that finally aggregate in crystals. Because of its rarity, CSH in bone
      marrow often makes diagnosis difficult. METHODS: A 57-year-old woman had IgA
      kappa monoclonal proteinemia and monoclonal proteinuria. In the bone marrow
      aspirate, plasma cells were initially counted less than what would be expected,
      whereas histiocytes with intracellular crystals were increased. Then, we used
      alpha-naphthyl acetate esterase (ANAE) staining to distinguish between true
      histiocytes and plasma cells. Immunostaining for kappa, CD138, CD56, and CD68 was
      performed on a bone marrow biopsy specimen. RESULTS: True histiocytes containing
      crystalline inclusions were stained strongly for ANAE, while unstained cells with
      intracytoplasmic crystals represented plasma cells. The biopsy specimen revealed
      diffuse infiltration of CD138-positive plasma cells. We also confirmed the
      presence of plasma cells, histiocytes, and their crystallized inclusions with the
      immunostaining. The patient was finally diagnosed with plasma cell myeloma.
      CONCLUSIONS: The diagnosis was challenging; the bone marrow findings resembled
      features of other histiocytic disorders. The use of immunohistochemistry enabled
      the diagnosis of CSH in the presence of plasma cell myeloma.

PMID- 25596259
TI  - Bone marrow assessment in the diagnosis of acquired hemophagocytic
      lymphohistiocytosis in adults.

PMID- 25596260
TI  - Gallbladders: another source of radiation in the histology laboratory.

PMID- 25596261
TI  - Pathology and malpractice.

PMID- 25596262
TI  - Mutations of ASXL1 and TET2 in aplastic anemia.

PMID- 25596263
TI  - A phase II study of vorinostat and rituximab for treatment of newly diagnosed and
      relapsed/refractory indolent non-Hodgkin lymphoma.
AB  - This study examines the activity and tolerability of a regimen combining
      vorinostat and rituximab in patients with indolent B-cell non-Hodgkin lymphoma. A
      total of 28 patients with newly diagnosed or relapsed/refractory follicular,
      marginal zone, or mantle cell lymphoma, with 4 or less prior therapies were
      eligible for this open-label phase II study. Oral vorinostat 200 mg was
      administered twice daily on days 1-14 along with 375 mg/m(2) of intravenous
      rituximab on day 1 of a 21-day cycle, continuing until disease progression or
      unacceptable toxicity. Primary end point was objective response rate, with
      secondary end points of progression-free survival, time to progression, duration
      of response, safety, and tolerability. Median follow up was 25.6 months and
      median number of vorinostat cycles was 11.5. Overall response rate was 46% for
      all patients, 67% for previously untreated, and 41% for relapsed/refractory
      patients. Median progression-free survival was 29.2 months for all patients, 18.8
      months for previously treated patients, and not reached for untreated patients.
      The regimen was well tolerated over long treatment periods with the most common
      grade 3/4 adverse events being asymptomatic thrombosis, neutropenia,
      thrombocytopenia, lymphopenia, and fatigue. The vorinostat/rituximab combination
      exhibits activity in indolent B-cell non-Hodgkin lymphoma with an acceptable
      safety profile and durable responses. Re-treatment was effective in 2 of 3
      relapsing responders. This phase II clinical trial was registered at
      clinicaltrials.gov identifier: 00720876. 

PMID- 25596264
TI  - Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non
      interventional, observational study from the European Research Initiative on
      Chronic Lymphocytic Leukemia.
AB  - We report the largest retrospective, phase IV non-interventional, observational
      study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis
      chronic lymphocytic leukemia. Total number of patients was 103; median age was 65
      years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13),
      including, in most cases, rituximab-, fludarabine- and alemtuzumab-based
      regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were
      considered to be directly related to ofatumumab. Grade 3-4 toxicities included
      neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever
      (3%). Two heavily pre-treated patients developed progressive multifocal
      leukoencephalopathy. On an intention-to-treat analysis, the overall response rate
      was 22% (3 complete response, 1 incomplete complete response). Median progression
      free and overall survival times were 5 and 11 months, respectively. This study
      confirms in a daily-life setting the feasibility and acceptable toxicity of
      ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete
      response rate, however, was low. Therefore, treatment with ofatumumab should be
      moved to earlier phases of the disease. Ideally, this should be done in
      combination with other agents, as recently approved for ofatumumab plus
      chlorambucil as front-line treatment for patients unfit for fludarabine. This
      study is registered at clinicaltrials.gov identifier:01453062. 

PMID- 25596265
TI  - Excess of heme induces tissue factor-dependent activation of coagulation in mice.
AB  - An excess of free heme is present in the blood during many types of hemolytic
      anemia. This has been linked to organ damage caused by heme-mediated oxidative
      stress and vascular inflammation. We investigated the mechanism of heme-induced
      coagulation activation in vivo. Heme caused coagulation activation in wild-type
      mice that was attenuated by an anti-tissue factor antibody and in mice expressing
      low levels of tissue factor. In contrast, neither factor XI deletion nor
      inhibition of factor XIIa-mediated factor XI activation reduced heme-induced
      coagulation activation, suggesting that the intrinsic coagulation pathway is not
      involved. We investigated the source of tissue factor in heme-induced coagulation
      activation. Heme increased the procoagulant activity of mouse macrophages and
      human PBMCs. Tissue factor-positive staining was observed on leukocytes isolated
      from the blood of heme-treated mice but not on endothelial cells in the lungs.
      Furthermore, heme increased vascular permeability in the mouse lungs, kidney and
      heart. Deletion of tissue factor from either myeloid cells, hematopoietic or
      endothelial cells, or inhibition of tissue factor expressed by non-hematopoietic
      cells did not reduce heme-induced coagulation activation. However, heme-induced
      activation of coagulation was abolished when both non-hematopoietic and
      hematopoietic cell tissue factor was inhibited. Finally, we demonstrated that
      coagulation activation was partially attenuated in sickle cell mice treated with
      recombinant hemopexin to neutralize free heme. Our results indicate that heme
      promotes tissue factor-dependent coagulation activation and induces tissue factor
      expression on leukocytes in vivo. We also demonstrated that free heme may
      contribute to thrombin generation in a mouse model of sickle cell disease. 

PMID- 25596266
TI  - The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do
      not benefit from doxorubicin: FIL-FOLL study.
AB  - Though most follicular lymphoma biomarkers rely on tumor features, the host
      genetic background may also be relevant for outcome. Here we aimed at verifying
      the contribution of candidate polymorphisms of FCgamma receptor, DNA repair and
      detoxification genes to prognostic stratification of follicular lymphoma treated
      with immunochemotherapy. The study was based on 428 patients enrolled in the
      FOLL05 prospective trial that compared three standard-of-care regimens (rituximab
      cyclophosphamide-vincristine-prednisone versus rituximab-cyclophosphamide
      doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for
      the first line therapy of advanced follicular lymphoma. Polymorphisms were
      genotyped on peripheral blood DNA samples. The primary endpoint was time to
      treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested
      to influence the activity of rituximab as a single agent, did not affect time to
      treatment failure in the pooled analysis of the three FOLL05 treatment arms that
      combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These
      results were consistent even when the analysis was conducted by intention to
      treat, indicating that different chemotherapy regimens and loads did not interact
      differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which
      regulates the genotoxic effect of doxorubicin, significantly affected time to
      treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin
      vincristine-prednisone arm (P=0.001; q<0.1), but not in arms in which patients
      did not receive doxorubicin (i.e., the rituximab-cyclophosphamide-vincristine
      prednisone and rituximab-fludarabine-mitoxantrone arms). The impact of MLH1 on
      time to treatment failure was independent after adjusting for the Follicular
      Lymphoma International Prognostic Index and other potential confounding variables
      by multivariate analysis. These data indicate that MLH1 genotype is a predictor
      of failure to benefit from rituximab-cyclophosphamide-doxorubicin-vincristine
      prednisone treatment in advanced follicular lymphoma and confirm that FCGR2A and
      FCGR3A polymorphisms have no impact when follicular lymphoma is treated with
      rituximab plus chemotherapy (clinicaltrials.gov identifier: NCT00774826). 

PMID- 25596268
TI  - BCOR and BCORL1 mutations in pediatric acute myeloid leukemia.

PMID- 25596267
TI  - ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by
      the German-Austrian Acute Myeloid Leukemia Study Group.
AB  - We studied 1696 patients (18 to 61 years) with acute myeloid leukemia for ASXL1
      mutations and identified these mutations in 103 (6.1%) patients. ASXL1 mutations
      were associated with older age (P<0.0001), male sex (P=0.041), secondary acute
      myeloid leukemia (P<0.0001), and lower values for bone marrow (P<0.0001) and
      circulating (P<0.0001) blasts. ASXL1 mutations occurred in all cytogenetic risk
      groups; normal karyotype (40%), other intermediate-risk cytogenetics (26%), high
      risk (24%) and low-risk (10%) cytogenetics. ASXL1 mutations were associated with
      RUNX1 (P<0.0001) and IDH2(R140) mutations (P=0.007), whereas there was an inverse
      correlation with NPM1 (P<0.0001), FLT3-ITD (P=0.0002), and DNMT3A (P=0.02)
      mutations. Patients with ASXL1 mutations had a lower complete remission rate (56%
      versus 74%; P=0.0002), and both inferior event-free survival (at 5 years: 15.9%
      versus 29.0%; P=0.02) and overall survival (at 5 years: 30.3% versus 45.7%;
      P=0.0004) compared to patients with wildtype ASXL1. In multivariable analyses,
      ASXL1 and RUNX1 mutation as a single variable did not have a significant impact
      on prognosis. However, we observed a significant interaction (P=0.04) for these
      mutations, in that patients with the genotype ASXL1(mutated)/RUNX1(mutated) had a
      higher risk of death (hazard ratio 1.8) compared to patients without this
      genotype. ASXL1 mutation, particularly in the context of a coexisting RUNX1
      mutation, constitutes a strong adverse prognostic factor in acute myeloid
      leukemia. 

PMID- 25596269
TI  - Differences in the erythropoiesis-hepcidin-iron store axis between hemoglobin H
      disease and beta-thalassemia intermedia.

PMID- 25596270
TI  - Subcutaneous versus intravenous bortezomib in patients with relapsed multiple
      myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021
      study.

PMID- 25596271
TI  - MLL partial tandem duplication leukemia cells are sensitive to small molecule
      DOT1L inhibition.

PMID- 25596272
TI  - Elevated hypercoagulability markers in hemoglobin SC disease.
AB  - Hemoglobin SC disease is a very prevalent hemoglobinopathy; however, very little
      is known about this condition specifically. There appears to be an increased risk
      of thromboembolic events in hemoglobin SC disease, but studies evaluating the
      hemostatic alterations are lacking. We describe the findings of a cross-sectional
      observational study evaluating coagulation activation markers in adult patients
      with hemoglobin SC, comparing them with those in sickle cell anemia patients and
      healthy controls. A total of 56 hemoglobin SC and 39 sickle cell anemia patients
      were included in the study, all in steady state, and 27 healthy controls. None of
      the patients was taking hydroxyurea. Hemoglobin SC patients had a significantly
      up-regulated relative expression of tissue factor, as well as elevations in
      thrombin-antithrombin complex and D-dimer, in comparison to controls (P<0.01).
      Hemoglobin SC patients had lower tissue factor expression, and thrombin
      antithrombin complex and D-dimer levels when compared to sickle cell anemia
      patients (P<0.05). Markers of endothelial activation (soluble thrombomodulin and
      soluble vascular cell adhesion molecule-1) and inflammation (tumor necrosis
      factor-alpha) were both significantly elevated in hemoglobin SC patients when
      compared to controls, being as high as the levels seen in patients with sickle
      cell anemia. Overall, in hemoglobin SC patients, higher hemolytic activity and
      inflammation were associated with a more intense activation of coagulation, and
      hemostatic activation was associated with two very prevalent chronic
      complications seen in hemoglobin SC disease: retinopathy and osteonecrosis. In
      summary, our results demonstrate that hemoglobin SC patients have a
      hypercoagulable state, although this manifestation was not as intense as that
      seen in sickle cell anemia. 

PMID- 25596274
TI  - TACC3-ch-TOG track the growing tips of microtubules independently of clathrin and
      Aurora-A phosphorylation.
AB  - The interaction between TACC3 (transforming acidic coiled coil protein 3) and the
      microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is
      evolutionarily conserved. Loading of TACC3-ch-TOG onto mitotic spindle
      microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the
      subsequent interaction of TACC3 with clathrin to form a microtubule-binding
      surface. Recent work indicates that TACC3 can track the plus-ends of microtubules
      and modulate microtubule dynamics in non-dividing cells via its interaction with
      ch-TOG. Whether there is a pool of TACC3-ch-TOG that is independent of clathrin
      in human cells, and what is the function of this pool, are open questions. Here,
      we describe the molecular interaction between TACC3 and ch-TOG that permits TACC3
      recruitment to the plus-ends of microtubules. This TACC3-ch-TOG pool is
      independent of EB1, EB3, Aurora-A phosphorylation and binding to clathrin. We
      also describe the distinct combinatorial subcellular pools of TACC3, ch-TOG and
      clathrin. TACC3 is often described as a centrosomal protein, but we show that
      there is no significant population of TACC3 at centrosomes. The delineation of
      distinct protein pools reveals a simplified view of how these proteins are
      organized and controlled by post-translational modification. 

PMID- 25596273
TI  - Multifunctional human CD56 low CD16 low natural killer cells are the prominent
      subset in bone marrow of both healthy pediatric donors and leukemic patients.
AB  - We phenotypically and functionally characterized a distinct CD56(low) natural
      killer cell subset based on CD16 expression levels in bone marrow and peripheral
      blood of healthy children and pediatric patients with acute lymphoblastic
      leukemia. Our findings demonstrate for the first time that CD56(low)CD16(low)
      natural killer cells are more abundant in bone marrow than in peripheral blood
      and that their frequency is further increased in children with acute
      lymphoblastic leukemia. Bone marrow and peripheral blood CD56(low)CD16(low)
      natural killer cells compared with CD56(low)CD16(high) natural killer cells
      express lower levels of killer inhibitory receptors, higher levels of CD27,
      CD127, CD122, CD25, but undetectable levels of CD57, suggesting that they have a
      higher proliferative and differentiation potential. Moreover, CD56(low)CD16(low)
      natural killer cells display higher levels of CXCR4 and undetectable levels of
      CX3CR1 and can be consistently and rapidly mobilized in peripheral blood in
      response to CXCR4 antagonist. Unlike CD56(low)CD16(high), both bone marrow and
      peripheral blood CD56(low)CD16(low) natural killer cells release IFNgamma
      following cytokine stimulation, and represent the major cytotoxic natural killer
      cell population against K562 or acute lymphoblastic leukemia target cells. All
      these data suggest that CD56(low)CD16(low) natural killer cells are
      multifunctional cells, and that the presence of hematologic malignancies affects
      their frequency and functional ability at both tumor site and in the periphery. 

PMID- 25596277
TI  - Highly efficient gene knockout by injection of TALEN mRNAs into oocytes and host
      transfer in Xenopus laevis.
AB  - Zinc-finger nucleases, transcription activator-like effector nucleases (TALENs)
      and the CRISPR/Cas (clustered regularly interspaced short palindromic
      repeats/CRISPR-associated proteins) system are potentially powerful tools for
      producing tailor-made knockout animals. However, their mutagenic activity is not
      high enough to induce mutations at all loci of a target gene throughout an entire
      tadpole. In this study, we present a highly efficient method for introducing gene
      modifications at almost all target sequences in randomly selected embryos. The
      gene modification activity of TALEN is enhanced by adopting the host-transfer
      technique. In our method, the efficiency is further improved by injecting TALEN
      mRNAs fused to the 3'UTR of the Xenopus DEADSouth gene into oocytes, which are
      then transferred into a host female frog, where they are ovulated and fertilized.
      The addition of the 3'UTR of the DEADSouth gene promotes mRNA translation in the
      oocytes and increases the expression of TALEN proteins to near-maximal levels
      three hours post fertilization (hpf). In contrast, TALEN mRNAs without this 3'UTR
      are translated infrequently in oocytes. Our data suggest that genomic DNA is more
      sensitive to TALEN proteins from fertilization to the midblastula (MBT) stage.
      Our method works by increasing the levels of TALEN proteins during the pre-MBT
      stages. 

PMID- 25596275
TI  - A proteomic study of mitotic phase-specific interactors of EB1 reveals a role for
      SXIP-mediated protein interactions in anaphase onset.
AB  - Microtubules execute diverse mitotic events that are spatially and temporally
      separated; the underlying regulation is poorly understood. By combining drug
      treatments, large-scale immunoprecipitation and mass spectrometry, we report the
      first comprehensive map of mitotic phase-specific protein interactions of the
      microtubule-end binding protein, EB1. EB1 interacts with some, but not all, of
      its partners throughout mitosis. We show that the interaction of EB1 with Astrin
      SKAP complex, a key regulator of chromosome segregation, is enhanced during
      prometaphase, compared to anaphase. We find that EB1 and EB3, another EB family
      member, can interact directly with SKAP, in an SXIP-motif dependent manner. Using
      an SXIP defective mutant that cannot interact with EB, we uncover two distinct
      pools of SKAP at spindle microtubules and kinetochores. We demonstrate the
      importance of SKAP's SXIP-motif in controlling microtubule growth rates and
      anaphase onset, without grossly disrupting spindle function. Thus, we provide the
      first comprehensive map of temporal changes in EB1 interactors during mitosis and
      highlight the importance of EB protein interactions in ensuring normal mitosis. 

PMID- 25596276
TI  - Shroom3 functions downstream of planar cell polarity to regulate myosin II
      distribution and cellular organization during neural tube closure.
AB  - Neural tube closure is a critical developmental event that relies on actomyosin
      contractility to facilitate specific processes such as apical constriction,
      tissue bending, and directional cell rearrangements. These complicated processes
      require the coordinated activities of Rho-Kinase (Rock), to regulate cytoskeletal
      dynamics and actomyosin contractility, and the Planar Cell Polarity (PCP)
      pathway, to direct the polarized cellular behaviors that drive convergent
      extension (CE) movements. Here we investigate the role of Shroom3 as a direct
      linker between PCP and actomyosin contractility during mouse neural tube
      morphogenesis. In embryos, simultaneous depletion of Shroom3 and the PCP
      components Vangl2 or Wnt5a results in an increased liability to NTDs and CE
      failure. We further show that these pathways intersect at Dishevelled, as Shroom3
      and Dishevelled 2 co-distribute and form a physical complex in cells. We observed
      that multiple components of the Shroom3 pathway are planar polarized along
      mediolateral cell junctions in the neural plate of E8.5 embryos in a Shroom3 and
      PCP-dependent manner. Finally, we demonstrate that Shroom3 mutant embryos exhibit
      defects in planar cell arrangement during neural tube closure, suggesting a role
      for Shroom3 activity in CE. These findings support a model in which the Shroom3
      and PCP pathways interact to control CE and polarized bending of the neural plate
      and provide a clear illustration of the complex genetic basis of NTDs. 

PMID- 25596278
TI  - Hormonal regulation of colour change in eyes of a cryptic fish.
AB  - Colour change of the skin in lower vertebrates such as fish has been a subject of
      great scientific and public interest. However, colour change also takes place in
      eyes of fish and while an increasing amount of data indicates its importance in
      behaviour, very little is known about its regulation. Here, we report that both
      eye and skin coloration change in response to white to black background
      adaptation in live sand goby Pomatoschistus minutes, a bentic marine fish.
      Through in vitro experiments, we show that noradrenaline and melanocyte
      concentrating hormone (MCH) treatments cause aggregation of pigment organelles in
      the eye chromatophores. Daylight had no aggregating effect. Combining forskolin
      to elevate intracellular cyclic adenosine monophosphate (cAMP) with MCH resulted
      in complete pigment dispersal and darkening of the eyes, whereas combining
      prolactin, adrenocorticotrophic hormone (ACTH) or melanocyte stimulating hormone
      (alpha-MSH) with MCH resulted in more yellow and red eyes. ACTH and MSH also
      induced dispersal in the melanophores, resulting in overall darker eyes. By
      comparing analysis of eyes, skin and peritoneum, we conclude that the regulation
      pattern is similar between these different tissues in this species which is
      relevant for the cryptic life strategy of this species. With the exception of
      ACTH which resulted in most prominent melanophore pigment dispersal in the eyes,
      all other treatments provided similar results between tissue types. To our
      knowledge, this is the first study that has directly analysed hormonal regulation
      of physiological colour change in eyes of fish. 

PMID- 25596280
TI  - Noninvasive continuous cardiac output monitoring in perioperative and intensive
      care medicine.
AB  - The determination of blood flow, i.e. cardiac output, is an integral part of
      haemodynamic monitoring. This is a review on noninvasive continuous cardiac
      output monitoring in perioperative and intensive care medicine. We present the
      underlying principles and validation data of the following technologies: thoracic
      electrical bioimpedance, thoracic bioreactance, vascular unloading technique,
      pulse wave transit time, and radial artery applanation tonometry. According to
      clinical studies, these technologies are capable of providing cardiac output
      readings noninvasively and continuously. They, therefore, might prove to be
      innovative tools for the assessment of advanced haemodynamic variables at the
      bedside. However, for most technologies there are conflicting data regarding the
      measurement performance in comparison with reference methods for cardiac output
      assessment. In addition, each of the reviewed technology has its own limitations
      regarding applicability in the clinical setting. In validation studies comparing
      cardiac output measurements using these noninvasive technologies in comparison
      with a criterion standard method, it is crucial to correctly apply statistical
      methods for the assessment of a technology's accuracy, precision, and trending
      capability. Uniform definitions for 'clinically acceptable agreement' between
      innovative noninvasive cardiac output monitoring systems and criterion standard
      methods are currently missing. Further research must aim to further develop the
      different technologies for noninvasive continuous cardiac output determination
      with regard to signal recording, signal processing, and clinical applicability.

PMID- 25596281
TI  - Multiple myeloma yields to CD38 inhibitors.

PMID- 25596279
TI  - Tyrosine motifs are required for prestin basolateral membrane targeting.
AB  - Prestin is targeted to the lateral wall of outer hair cells (OHCs) where its
      electromotility is critical for cochlear amplification. Using MDCK cells as a
      model system for polarized epithelial sorting, we demonstrate that prestin uses
      tyrosine residues, in a YXXPhi motif, to target the basolateral surface. Both
      Y520 and Y667 are important for basolateral targeting of prestin. Mutation of
      these residues to glutamine or alanine resulted in retention within the Golgi and
      delayed egress from the Golgi in Y667Q. Basolateral targeting is restored upon
      mutation to phenylalanine suggesting the importance of a phenol ring in the
      tyrosine side chain. We also demonstrate that prestin targeting to the
      basolateral surface is dependent on AP1B (MU1B), and that prestin uses
      transferrin containing early endosomes in its passage from the Golgi to the
      basolateral plasma membrane. The presence of AP1B (MU1B) in OHCs, and parallels
      between prestin targeting to the basolateral surface of OHCs and polarized
      epithelial cells suggest that outer hair cells resemble polarized epithelia
      rather than neurons in this important phenotypic measure. 

PMID- 25596283
TI  - SND1 Acts Downstream of TGFbeta1 and Upstream of Smurf1 to Promote Breast Cancer
      Metastasis.
AB  - SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human
      cancers, where it has been assigned multiple functional roles. In this study, we
      report its association with the TGFbeta1 signaling pathway, which promotes
      epithelial-mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in
      breast cancer tissues, in particular in primary invasive ductal carcinomas.
      Transcriptional activation of the SND1 gene was controlled by the TGFbeta1/Smad
      pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter
      region contained several Smad-specific recognition domains (RD motifs), which
      were recognized and bound by the Smad complex that enhanced the transcriptional
      activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin
      ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation
      in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell
      adhesion, increased cell migration and invasion, and promoted metastasis.
      Overall, our results define a novel role for SND1 in regulating breast
      tumorigenesis and metastasis.

PMID- 25596282
TI  - Tumorigenic activity of merkel cell polyomavirus T antigens expressed in the
      stratified epithelium of mice.
AB  - Merkel cell polyomavirus (MCPyV) is frequently associated with Merkel cell
      carcinoma (MCC), a highly aggressive neuroendocrine skin cancer. Most MCC tumors
      contain integrated copies of the viral genome with persistent expression of the
      MCPyV large T (LT) and small T (ST) antigen. MCPyV isolated from MCC typically
      contains wild-type ST but truncated forms of LT that retain the N-terminus but
      delete the C-terminus and render LT incapable of supporting virus replication. To
      determine the oncogenic activity of MCC tumor-derived T antigens in vivo, a
      conditional, tissue-specific mouse model was developed. Keratin 14-mediated Cre
      recombinase expression induced expression of MCPyV T antigens in stratified
      squamous epithelial cells and Merkel cells of the skin epidermis. Mice expressing
      MCPyV T antigens developed hyperplasia, hyperkeratosis, and acanthosis of the
      skin with additional abnormalities in whisker pads, footpads, and eyes. Nearly
      half of the mice also developed cutaneous papillomas. Evidence for neoplastic
      progression within stratified epithelia included increased cellular
      proliferation, unscheduled DNA synthesis, increased E2F-responsive genes levels,
      disrupted differentiation, and presence of a DNA damage response. These results
      indicate that MCPyV T antigens are tumorigenic in vivo, consistent with their
      suspected etiologic role in human cancer.

PMID- 25596286
TI  - Keratoconus in an adult with 22q11.2 deletion syndrome.
AB  - 22q11.2 Deletion syndrome is one of the most common microdeletional syndromes,
      with an incidence of 1:4000 live-births, and potentially affects every organ in
      the body. More than 180 associated clinical features have been reported and not
      one phenotypic feature is present in 100% of cases. Ocular manifestations
      reported based on early childhood examinations include eyelid hooding,
      strabismus, posterior embryotoxon, retinal vessel tortuosity and refractive
      errors. Keratoconus has been reported once before in association with 22q11.2
      deletion syndrome in a young adult. We report the second case of keratoconus in
      association with 22q11.2 deletion syndrome. 

PMID- 25596287
TI  - Uterine artery embolisation for acute dysfunctional uterine bleeding with failed
      medical therapy: a novel approach to management.
AB  - A 35-year-old woman with a history of three previous caesarean sections was
      admitted with acute dysfunctional uterine bleeding (DUB) complicated by anaemia;
      she had a haemoglobin level of 5.3 g/dL, requiring multiple blood transfusions.
      Investigations performed excluded pelvic pathology and haematological causes for
      her acute DUB. Despite the use of various pharmacological agents, her bleeding
      persisted and she eventually underwent uterine artery embolisation (UAE) to
      arrest bleeding. She was well postprocedure and was discharged on combined oral
      contraceptives. However, she presented a year later with another episode of acute
      DUB that required a repeat UAE. This case report summarises the use of UAE in the
      management of acute DUB following failed medical therapy. 

PMID- 25596284
TI  - ERBB3-independent activation of the PI3K pathway in EGFR-mutant lung
      adenocarcinomas.
AB  - ERBB3, a member of the EGFR family of receptor tyrosine kinases, has been
      implicated in activation of the PI3K pathway in human lung adenocarcinomas driven
      by EGFR mutations. We investigated the contribution of ERBB3 to the initiation,
      progression, and therapeutic response of EGFR-induced lung adenocarcinomas using
      tetracycline- and tamoxifen-inducible transgenic mouse models. Deletion of Erbb3
      at the time of induction of mutant EGFR had no effect on tumorigenesis,
      demonstrating that ERBB3 is not required to initiate tumorigenesis. Tumors that
      developed in the absence of ERBB3 remained sensitive to EGFR tyrosine kinase
      inhibitors and retained activation of the PI3K-AKT pathway. Interestingly, acute
      loss of Erbb3 suppressed further growth of established EGFR(L858R)-mediated lung
      tumors. Four weeks after deletion of Erbb3, the tumors exhibited phosphorylation
      of EGFR, of the adaptor proteins GAB1 and GAB2, and of the downstream signaling
      molecules AKT and ERK, suggesting that alternative signaling pathways could
      compensate for loss of Erbb3. Similar to our observations with mouse tumors, we
      found that GAB adaptor proteins play a role in ERBB3-independent activation of
      the PI3K pathway by mutant EGFR in EGFR-mutant human cell lines. Finally, in such
      cell lines, increased levels of phosphorylation of ERBB2 or MET were associated
      with reduced sensitivity to acute loss of ERBB3, suggesting remarkable plasticity
      in the signaling pathways regulated by mutant EGFR with important therapeutic
      implications.

PMID- 25596288
TI  - Metronidazole-induced encephalopathy after prolonged metronidazole course for
      treatment of C. difficile colitis.
AB  - A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing
      prolonged treatment with metronidazole was admitted to hospital for altered
      mentation, slurred speech and weakness. She was diagnosed with metronidazole
      induced encephalopathy, confirmed with brain MRI and improved when the offending
      agent was removed. This case report highlights encephalopathy as a complication
      of prolonged metronidazole treatment, which has become more common in clinical
      practice for the treatment of C. difficile infection. 

PMID- 25596289
TI  - Renal cell carcinoma with proliferative lupus nephritis.
AB  - We report a case of renal cell carcinoma diagnosed after a patient was treated
      successfully with intravenous cyclophosphamide for her active proliferative lupus
      nephritis (classes III and V). After the intravenous cyclophosphamide regimen,
      the patient was asymptomatic with persistent microscopic haematuria, and no
      proteinuria. The renal cell carcinoma was located on the left kidney;
      incidentally, this was where the initial renal biopsy was done to diagnose lupus
      nephritis. 

PMID- 25596290
TI  - 'Stump appendicitis': postappendectomy appendicitis.

PMID- 25596291
TI  - Cerebral infarction accompanied by cerebral bleeding in patients receiving
      apixaban.

PMID- 25596292
TI  - Angiosarcoma of common iliac vein.
AB  - Angiosarcoma is a rare malignant tumour of endothelial cells. Primary
      angiosarcoma of venous origin is extremely rare, and has a very poor prognosis. A
      63-year-old woman with retroperitoneal mass underwent en bloc resection on a part
      of iliac vein followed by adjuvant radiotherapy. No recurrence was detected
      during 3 years of follow-up.

PMID- 25596294
TI  - Plasma cell gingivitis with severe alveolar bone loss.
AB  - Plasma cell gingivitis is a rare benign condition of the gingiva characterised by
      sharply demarcated erythaematous and oedematous gingiva often extending up to the
      muco gingival junction. It is considered a hypersensitive reaction. It presents
      clinically as a diffuse, erythaematous and papillary lesion of the gingiva, which
      frequently bleeds, with minimal trauma. This paper presents a case of a 42-year
      old man who was diagnosed with plasma cell gingivitis, based on the presence of
      plasma cells in histological sections, and severe alveolar bone loss at the
      affected site, which was managed by surgical intervention. 

PMID- 25596293
TI  - Gastropericardial fistula after Roux-en-Y bypass for reflux disease.
AB  - A 49-year-old man was admitted to his local hospital with a 3-day history of left
      sided chest pain which started after a coughing paroxysm. His surgical history
      included laparoscopic Toupet fundoplication 30 months earlier and revisional
      reflux surgery (Roux-en-Y gastric bypass) 11 months earlier. On admission, he was
      found to be tachycardic at 110 bpm, hypotensive (90/65 mm Hg). He had ST
      depression in ECG leads V2-5 with a normal troponin I level. Chest radiography
      indicated a pneumopericardium which prompted referral to the oesophagogastric
      surgery unit. Endoscopy and CT with oral contrast confirmed a gastropericardial
      fistula. This was managed by total gastrectomy through a left thoracoabdominal
      approach. The patient was discharged home 2 months later. We report the fourth
      case of gastropericardial fistula in the literature as a long-term complication
      of Roux-en-Y gastric bypass with a favourable outcome and mini literature review.

PMID- 25596295
TI  - Cutaneous melioidosis in a healthy Danish man after travelling to South-East
      Asia.
AB  - A healthy Danish man presented with infected prepatellar bursitis 8 months after
      being involved in a car accident in Malaysia resulting in exposure of a
      laceration of his knee to stagnant water. Tissue samples grew Burkholderia
      pseudomallei and diagnostic work up revealed no secondary foci. The patient was
      successfully treated with surgical debridement and 3 months of oral trimethoprim
      sulfamethoxazole. At 6 months follow-up the patient was without relapse.

PMID- 25596296
TI  - Amyloidosis of the renal pelvis: a harbinger of mammary carcinoma?
AB  - We describe a rare case of light chain immunoglobulin amyloid (AL) accumulation
      in the central and lower pole renal calyces. Our patient, a woman aged 60,
      presented with several episodes of gross haematuria. Radiological imaging
      detected a filling defect in the left renal pelvis. Rigid ureteroscopy showed a
      corresponding mucosal abnormality resembling transitional cell carcinoma. A
      definitive preoperative tissue diagnosis could not be reached. Laparoscopic
      assisted left nephroureterectomy was indicated. Histopathological examination
      excluded malignancy, revealing congophilic deposits of submucosal amyloid. A
      constellation of findings confirmed localised or primary amyloidosis with an AL
      immunophenotype but no evidence of clonal B-cell disease in the amyloid
      associated lymphoplasmacytic cell infiltrate. Investigation for systemic plasma
      cell dyscrasia and echocardiography and scintigraphy for visceral amyloid
      deposits were negative for systemic disease. At a follow-up period of 30 months,
      there is no recurrence. However, our patient was diagnosed with breast cancer 21
      months ago.

PMID- 25596297
TI  - Laying bare the nude mouse gene.

PMID- 25596298
TI  - Pillars article: new member of the winged-helix protein family disrupted in mouse
      and rat nude mutations. Nature. 1994. 372: 103-107.

PMID- 25596301
TI  - Correction: Role of Neutrophils in IL-17-Dependent Immunity to Mucosal
      Candidiasis.

PMID- 25596300
TI  - Retraction: Guanosine inhibits CD40 receptor expression and function induced by
      cytokines and beta amyloid in mouse microglia cells.

PMID- 25596299
TI  - The acute respiratory distress syndrome: from mechanism to translation.
AB  - The acute respiratory distress syndrome (ARDS) is a form of severe hypoxemic
      respiratory failure that is characterized by inflammatory injury to the alveolar
      capillary barrier, with extravasation of protein-rich edema fluid into the
      airspace. Although many modalities to treat ARDS have been investigated over the
      past several decades, supportive therapies remain the mainstay of treatment. In
      this article, we briefly review the definition, epidemiology, and pathophysiology
      of ARDS and present emerging aspects of ARDS pathophysiology that encompass
      modulators of the innate immune response, damage signals, and aberrant
      proteolysis that may serve as a foundation for future therapeutic targets. 

PMID- 25596302
TI  - Correction: AID-Initiated DNA Lesions Are Differentially Processed in Distinct B
      Cell Populations.

PMID- 25596303
TI  - Interleukin 10-Dominant Immune Response and Increased Risk of Cutaneous
      Leishmaniasis After Natural Exposure to Lutzomyia intermedia Sand Flies.
AB  - BACKGROUND: Leishmaniasis is caused by parasites transmitted to the vertebrate
      host by infected sand flies. During transmission, the vertebrate host is also
      inoculated with sand fly saliva, which exerts powerful immunomodulatory effects
      on the host's immune response. METHODS: We conducted a prospective cohort
      analysis to characterize the human immune response to Lutzomyia intermedia saliva
      in 264 individuals, from an area for cutaneous leishmaniasis (CL) caused by
      Leishmania braziliensis. RESULTS: Antibodies were found in 150 individuals
      (56.8%); immunoglobulin G1 and G4 were the predominant subclasses. Recall
      responses to salivary gland sonicate showed elevated production of interleukin 10
      (IL-10), interleukin 13, interferon gamma, CXCL9, and CCL2 compared with
      controls. CD4(+)CD25(+) T cells, including Foxp3(+) cells, were the main source
      of IL-10. L. braziliensis replication was increased (P < .05) in macrophages
      cocultured with saliva-stimulated lymphocytes from exposed individuals and
      addition of anti-IL-10 reverted this effect. Positive correlation between
      antibody response to saliva and cellular response to Leishmania was not found.
      Importantly, individuals seropositive to saliva are 2.1 times more likely to
      develop CL (relative risk, 2.1; 95% confidence interval, 1.07-4.2; P < .05).
      CONCLUSIONS: Exposure to L. intermedia sand flies skews the human immune
      response, facilitating L. braziliensis survival in vitro, and increases the risk
      of developing CL.

PMID- 25596304
TI  - Antibody to reduction modifiable protein increases the bacterial burden and the
      duration of gonococcal infection in a mouse model.
AB  - Antibodies against reduction modifiable protein (anti-Rmp Abs) can block
      complement-dependent killing of Neisseria gonorrhoeae by otherwise bactericidal
      Abs. An anti-lipooligosaccharide bactericidal monoclonal Ab (mAb) 2C7, a
      gonococcal vaccine candidate Ab, attenuates vaginal colonization by gonococci in
      BALB/c mice. Here we show that anti-Rmp Abs block the efficacy of mAb 2C7 in mice
      in a dose-dependent manner. Anti-Rmp Abs also counteract 2C7-mediated enhancement
      of C3 deposition on gonococci in vivo. The mouse model will prove useful to study
      how blocking Abs influence the efficacy of gonococcal vaccines. Preexisting anti
      Rmp Abs will be an important consideration in evaluating the efficacy of
      gonococcal vaccine candidates. 

PMID- 25596305
TI  - New partners for protein kinases.

PMID- 25596306
TI  - COL4A3 mutations cause focal segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is a histologically identifiable
      glomerular injury often leading to proteinuria and renal failure. To identify its
      causal genes, whole-exome sequencing and Sanger sequencing were performed on a
      large Chinese cohort that comprised 40 FSGS families, 50 sporadic FSGS patients,
      9 independent autosomal recessive Alport's syndrome (ARAS) patients, and 190
      ethnically matched healthy controls. Patients with extrarenal manifestations,
      indicating systemic diseases or other known hereditary renal diseases, were
      excluded. Heterozygous COL4A3 mutations were identified in five (12.5%) FSGS
      families and one (2%) sporadic FSGS patient. All identified mutations disrupted
      highly conserved protein sequences and none of them was found in either public
      databases or the 190 healthy controls. Of the FSGS patients with heterozygous
      COL4A3 mutations, segmental thinning of the glomerular base membrane (GBM) was
      only detected in the patient with electronic microscopy examination results
      available. Five ARAS patients (55.6%) had homozygous or compound-heterozygous
      mutations in COL4A3 or COL4A4. Serious changes in the GBM, hearing loss, and
      ocular abnormalities were found in 100%, 80%, and 40% of the ARAS patients,
      respectively. Overall, a new subgroup of FSGS patients resulting from
      heterozygous COL4A3 mutations was identified. The mutations are relatively
      frequent in families diagnosed with inherited forms of FSGS. Thus, we suggest
      screening for COL4A3 mutations in familial FSGS patients. 

PMID- 25596308
TI  - mirTrios: an integrated pipeline for detection of de novo and rare inherited
      mutations from trios-based next-generation sequencing.
AB  - OBJECTIVES: Recently, several studies documented that de novo mutations (DNMs)
      play important roles in the aetiology of sporadic diseases. Next-generation
      sequencing (NGS) enables variant calling at single-base resolution on a genome
      wide scale. However, accurate identification of DNMs from NGS data still remains
      a major challenge. We developed mirTrios, a web server, to accurately detect DNMs
      and rare inherited mutations from NGS data in sporadic diseases. METHODS: The
      expectation-maximisation (EM) model was adopted to accurately identify DNMs from
      variant call files of a trio generated by GATK (Genome Analysis Toolkit). The
      GATK results, which contain certain basic properties (such as PL, PRT and PART),
      are iteratively integrated into the EM model to strike a threshold for DNMs
      detection. Training sets of true and false positive DNMs in the EM model were
      built from whole genome sequencing data of 64 trios. RESULTS: With our in-house
      whole exome sequencing datasets from 20 trios, mirTrios totally identified 27
      DNMs in the coding region, 25 of which (92.6%) are validated as true positives.
      In addition, to facilitate the interpretation of diverse mutations, mirTrios can
      also be employed in the identification of rare inherited mutations. Embedded with
      abundant annotation of DNMs and rare inherited mutations, mirTrios also supports
      known diagnostic variants and causative gene identification, as well as the
      prioritisation of novel and promising candidate genes. CONCLUSIONS: mirTrios
      provides an intuitive interface for the general geneticist and clinician, and can
      be widely used for detection of DNMs and rare inherited mutations, and annotation
      in sporadic diseases. mirTrios is freely available at
      http://centre.bioinformatics.zj.cn/mirTrios/.

PMID- 25596309
TI  - Plasma globotriaosylsphingosine in relation to phenotypes of Fabry disease.
AB  - BACKGROUND: Fabry disease (FD), a lysosomal storage disorder caused by alpha
      galactosidase A (GLA) gene variants, has a heterogeneous phenotype. GLA variants
      can lead to classical FD, an attenuated non-classical phenotype, or no disease at
      all. This study investigates the value of plasma globotriaosylsphingosine
      (lysoGb3) to distinguish between these groups. This is of particular importance
      in the diagnosis of individuals with a GLA variant and an uncertain diagnosis of
      FD, lacking characteristic features of classical FD. METHODS: Subjects with GLA
      variants were grouped as classical, non-classical, uncertain or no FD, using
      strict phenotypical, biochemical and histological criteria. Plasma lysoGb3 was
      assessed by LC/MS/MS (normal <= 0.6 nmol/L). RESULTS: 154 subjects were grouped
      into classical (38 males (M), 66 females (F)), non-classical (13 M, 14 F),
      uncertain (5M, 9 F) or no FD (6M, 3F). All subjects with a classical phenotype
      had elevated lysoGb3 values (M: range 45-150, F: 1.5-41.5). LysoGb3 values in
      patients with a non-classical phenotype (M: 1.3-35.7, F: 0.5-2.0) were different
      from healthy controls (M: p<0.01, F: p<0.05), but females overlapped with
      controls. In the no-FD group, lysoGb3 was normal. CONCLUSIONS: LysoGb3 is a
      reliable diagnostic tool to discern classical FD from subjects without FD. This
      study suggests that the same applies to patients with a non-classical phenotype.
      LysoGb3 values of female patients overlap with controls. Consequently, in
      uncertain cases, increased lysoGb3 values are very suggestive for FD, but normal
      values cannot exclude FD. Confirmation in larger cohorts and data on the
      specificity of small lysoGb3 increases are necessary.

PMID- 25596311
TI  - Editorial comment.

PMID- 25596310
TI  - Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH)
      genotypes promotes personalised medicine in phenylketonuria.
AB  - BACKGROUND: In phenylketonuria, genetic heterogeneity, frequent compound
      heterozygosity, and the lack of functional data for phenylalanine hydroxylase
      genotypes hamper reliable phenotype prediction and individualised treatment.
      METHODS: A literature search revealed 690 different phenylalanine hydroxylase
      genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We
      determined phenylalanine hydroxylase function of 30 frequent homozygous and
      compound heterozygous genotypes covering 55% of the study population, generated
      activity landscapes, and assessed the phenylalanine hydroxylase working range in
      the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space.
      RESULTS: Shared patterns in genotype-specific functional landscapes were linked
      to biochemical and pharmacological phenotypes, where (1) residual activity below
      3.5% was associated with classical phenylketonuria unresponsive to
      pharmacological treatment; (2) lack of defined peak activity induced loss of
      response to tetrahydrobiopterin; (3) a higher cofactor need was linked to
      inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response;
      and (4) residual activity above 5%, a defined peak of activity, and a normal
      cofactor need were associated with pharmacologically treatable mild phenotypes.
      In addition, we provide a web application for retrieving country-specific
      information on genotypes and genotype-specific phenylalanine hydroxylase function
      that warrants continuous extension, updates, and research on demand. CONCLUSIONS:
      The combination of genotype-specific functional analyses with biochemical,
      clinical, and therapeutic data of individual patients may serve as a powerful
      tool to enable phenotype prediction and to establish personalised medicine
      strategies for dietary regimens and pharmacological treatment in phenylketonuria.

PMID- 25596312
TI  - Editorial comment.

PMID- 25596314
TI  - Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic
      perspectives.
AB  - Chrysin, a naturally occurring flavone, abundantly found in numerous plant
      extracts including propolis and in honey is one of the most widely used herbal
      medicine in Asian countries. Nowadays, chrysin has become the foremost candidate
      exhibiting health benefits, owing to its multiple bioactivities such as
      antioxidant, anti-inflammatory, anti-allergic, anti-diabetic, anti-estrogenic,
      antibacterial and antitumor activities. Anticancer activity is most promising
      among the multiple pharmacological effects displayed by chrysin. In vitro and in
      vivo models have shown that chrysin inhibits cancer growth through induction of
      apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and
      metastasis without causing any toxicity and undesirable side effects to normal
      cells. Chrysin displays these effects through selective modulation of multiple
      cell signaling pathways which are linked to inflammation, survival, growth,
      angiogenesis, invasion and metastasis of cancer cells. This broad spectrum of
      antitumor activity in conjunction with low toxicity underscores the translational
      value of chrysin in cancer therapy. The present review highlights the
      chemopreventive and therapeutic effects, molecular targets and antineoplastic
      mechanisms that contribute to the observed anticancer activity of chrysin. 

PMID- 25596313
TI  - Efficacy and safety of simeprevir with PegIFN/ribavirin in naive or experienced
      patients infected with chronic HCV genotype 4.
AB  - BACKGROUND & AIMS: Simeprevir (SMV) is a once-daily (QD), oral hepatitis C virus
      (HCV) NS3/4A protease inhibitor approved for treatment of genotype (GT) 1 and GT4
      infection. This Phase III, open-label, single-arm study (RESTORE; NCT01567735)
      evaluated efficacy/safety of SMV with peginterferon-alpha-2a/ribavirin (PR) in
      patients with chronic HCV GT4 infection. METHODS: 107 patients were included.
      Treatment-naive (n=35) and prior relapse patients (n=22) received SMV 150mg QD+PR
      (12 weeks), followed by PR alone (12 or 36 weeks, response-guided [HCV RNA
      <25IU/ml detectable/undetectable at week 4 and <25IU/ml undetectable at week
      12]). Prior non-responders (partial, n=10; null, n=40) received SMV/PR (12
      weeks), followed by PR for 36 weeks. The primary endpoint was sustained virologic
      response 12 weeks after end of treatment (SVR12). RESULTS: Median age: 49.0years;
      28.0% Black/African; 7.5% IL28B CC; 28.8% METAVIR F4. Overall, 65.4% (70/107) of
      patients achieved SVR12 (82.9% [29/35] treatment-naive; 86.4% [19/22] prior
      relapsers; 60.0% [6/10] prior partial responders; 40.0% [16/40] prior null
      responders). In treatment-naive and prior relapser patients fulfilling response
      guided criteria for 24 weeks of treatment (88.6% [31/35] and 90.9% [20/22]),
      SVR12 rates were high: 93.5% [29/31] and 95.0% [19/20], respectively. Overall on
      treatment failure and relapse rates were 23.4% (25/107) and 14.6% (12/82),
      respectively. Adverse events (AEs) were mainly grade 1/2; serious AEs were
      infrequent (4.7%) and considered unrelated to SMV. CONCLUSIONS: Efficacy and
      safety of SMV 150mg QD for 12 weeks with PR in treatment-naive or -experienced
      patients with chronic HCV GT4 infection were in line with previous reports for
      HCV GT1 infection.

PMID- 25596315
TI  - Inhibition of Mer and Axl receptor tyrosine kinases leads to increased apoptosis
      and improved chemosensitivity in human neuroblastoma.
AB  - Ectopic expression of Mer and Axl receptor tyrosine kinases (RTKs) are frequently
      found in various cancers as known to promote oncogenesis by activating
      antiapoptotic signaling pathways. However, the roles of these receptors in
      neuroblastoma remain unclear. We found Mer and Axl was co-expressed in
      neuroblastoma patient samples and cell lines. Ligand-dependent Mer or Axl
      activation led to an increase in phosphorylated ERK1/2, AKT and FAK indicating
      roles for these RTKs in multiple oncogenic processes. Furthermore, Mer and Axl
      knockdown led to apoptosis and inhibition of migration as well as a significant
      increase in chemosensitivity in response to cisplatin and vincristine treatment.
      Taken together, our results demonstrated that inhibition of Mer and Axl improved
      apoptotic response and chemosensitivity in neuroblastoma, providing new insights
      into development of novel therapeutic strategies by targeting these oncogenes. 

PMID- 25596316
TI  - Reduced modulation of scanpaths in response to task demands in posterior cortical
      atrophy.
AB  - A difficulty in perceiving visual scenes is one of the most striking impairments
      experienced by patients with the clinico-radiological syndrome posterior cortical
      atrophy (PCA). However whilst a number of studies have investigated perception of
      relatively simple experimental stimuli in these individuals, little is known
      about multiple object and complex scene perception and the role of eye movements
      in posterior cortical atrophy. We embrace the distinction between high-level (top
      down) and low-level (bottom-up) influences upon scanning eye movements when
      looking at scenes. This distinction was inspired by Yarbus (1967), who
      demonstrated how the location of our fixations is affected by task instructions
      and not only the stimulus' low level properties. We therefore examined how
      scanning patterns are influenced by task instructions and low-level visual
      properties in 7 patients with posterior cortical atrophy, 8 patients with typical
      Alzheimer's disease, and 19 healthy age-matched controls. Each participant viewed
      10 scenes under four task conditions (encoding, recognition, search and
      description) whilst eye movements were recorded. The results reveal significant
      differences between groups in the impact of test instructions upon scanpaths.
      Across tasks without a search component, posterior cortical atrophy patients were
      significantly less consistent than typical Alzheimer's disease patients and
      controls in where they were looking. By contrast, when comparing search and non
      search tasks, it was controls who exhibited lowest between-task similarity
      ratings, suggesting they were better able than posterior cortical atrophy or
      typical Alzheimer's disease patients to respond appropriately to high-level needs
      by looking at task-relevant regions of a scene. Posterior cortical atrophy
      patients had a significant tendency to fixate upon more low-level salient parts
      of the scenes than controls irrespective of the viewing task. The study provides
      a detailed characterisation of scene perception abilities in posterior cortical
      atrophy and offers insights into the mechanisms by which high-level cognitive
      schemes interact with low-level perception. 

PMID- 25596317
TI  - Heterogeneity in mechanisms influencing glucocorticoid sensitivity: the need for
      a systems biology approach to treatment of glucocorticoid-resistant inflammation.
AB  - Glucocorticoids (GCs) have impressive anti-inflammatory and immunosuppressive
      effects and show a diversity of actions across a variety of cell phenotypes.
      Implicit in efforts to optimize GCs as anti-inflammatory agents for any or all
      indications is the notion that the relevant mechanism(s) of action of GCs are
      fully elucidated. However, recent advances in understanding GC signalling
      mechanisms have revealed remarkable complexity and contextual dependence, calling
      into question whether the mechanisms of action are sufficiently well-described to
      embark on optimization. In the current review, we address evidence for
      differences in the mechanism of action in different cell types and contexts, and
      discuss contrasts in mechanisms of glucocorticoid insensitivity, with a focus on
      asthma and Chronic Obstructive Pulmonary Disease (COPD). Given this complexity,
      we consider the potential breadth of impact and selectivity of strategies
      directed to reversing the glucocorticoid insensitivity.

PMID- 25596318
TI  - Intentional and unintentional multi-joint movements: their nature and structure
      of variance.
AB  - We tested predictions of a hierarchical scheme on the control of natural
      movements with referent body configurations. Subjects occupied an initial hand
      position against a bias force generated by a HapticMaster robot. A smooth force
      perturbation was applied to the hand consisting of an increase in the bias force,
      keeping it at a new level for 5s, and decreasing it back to the bias value. When
      the force returned to the bias value, the arm stopped at a position different
      from the initial one interpreted as an involuntary movement. We then asked
      subjects to make voluntary movements to targets corresponding to the measured end
      position of the unintentional movements. No target for hand orientation was used.
      The joint configuration variance was compared between intentional and
      unintentional movements within the framework of the uncontrolled manifold
      hypothesis. Our central hypothesis was that both unintentional and intentional
      movements would be characterized by structure of joint configuration variance
      reflecting task-specific stability of salient performance variables, such as hand
      position and orientation. The analysis confirmed that most variance at the final
      steady states was compatible with unchanged values of both hand position and
      orientation following both intentional and unintentional movements. We interpret
      unintentional movements as consequences of back-coupling between the actual and
      referent configurations at the task level. The results suggested that both
      intentional and unintentional movements resulted from shifts of the body referent
      configuration produced intentionally or as a result of the hypothesized back
      coupling. Inter-trial variance signature reflects similar task-specific stability
      properties of the system following both types of movements, intentional and
      unintentional. 

PMID- 25596321
TI  - Voluntary control of corticomuscular coherence through neurofeedback: a proof-of
      principle study in healthy subjects.
AB  - Corticomuscular coherence (CMC) relates to synchronization between activity in
      the motor cortex and the muscle activity. The strength of CMC can be affected by
      motor behavior. In a proof-of-principle study, we examined whether independent of
      motor output parameters, healthy subjects are able to voluntarily modulate CMC in
      a neurofeedback paradigm. Subjects received visual online feedback of their
      instantaneous CMC strength, which was calculated between an optimized spatial
      projection of multichannel electroencephalography (EEG) and electromyography
      (EMG) in an individually defined target frequency range. The neurofeedback
      training consisted of either increasing or decreasing CMC strength using a self
      chosen mental strategy while performing a simple motor task. Evaluation of
      instantaneous coherence showed that CMC strength was significantly larger when
      subjects had to increase than when to decrease CMC; this difference between the
      two task conditions did not depend on motor performance. The exclusion of
      confounding factors such as motor performance, attention and task complexity in
      study design provides evidence that subjects were able to voluntarily modify CMC
      independent of motor output parameters. Additional analysis further strengthened
      the assumption that the subjects' response was specifically shaped by the
      neurofeedback. In perspective, we suggest that CMC-based neurofeedback could
      provide a therapeutic approach in clinical conditions, such as motor stroke,
      where CMC is altered. 

PMID- 25596320
TI  - Effect of neurotoxic lesion of pedunculopontine nucleus in nigral and striatal
      redox balance and motor performance in rats.
AB  - Early degeneration of pedunculopontine nucleus (PPN) is considered part of
      changes that characterize premotor stages of Parkinson's disease (PD). In this
      paper, the effects of unilateral neurotoxic lesion of the PPN in motor execution
      and in the development of oxidative stress events in striatal and nigral tissues
      in rats were evaluated. The motor performance was assessed using the beam test
      (BT) and the cylinder test (CT). Nigral and striatal redox balance, was studied
      by means of biochemical indicators such as malondialdehyde (MDA), nitric oxide
      (NO) and the catalase enzymatic activity (CAT EA). Lesioned rats showed fine
      motor dysfunction expressed both as an increase in the length (p<0.001) and
      deviation (p<0.001) of the traveled path and also in the time spent (p<0.01) in
      the circular small beam (CBS) (p<0.01) in comparison with control groups. In
      addition, the lesioned rats group presented a right asymmetry index greater than
      0.5 which is consistent with a significant increase in the percentage of use of
      the right forelimb (ipsilateral to the lesion), compared with the control group
      (p<0.05). Biochemical studies revealed that after 48-h PPN neurotoxic injury, the
      CAT EA showed a significant increase in the subtantia nigra pars compacta (SNpc)
      (p<0.05). This significant increase of CAT EA persisted in the nigral tissue
      (p<0.001) and reached the striatal tissue (p<0.001) seven days after PPN injury.
      Also at seven days post-injury PPN, increased concentrations of MDA (p<0.01) and
      a tendency to decrease in the concentrations of NO in both structures (SNpc and
      striatum) were found. The events associated with the generation of free radicals
      at nigral and striatal levels, can be part of the physiological mechanisms
      underlying motor dysfunction in rats with unilateral PPN neurotoxic lesion. 

PMID- 25596322
TI  - Clinical phenotypes in patients with knee osteoarthritis: a study in the
      Amsterdam osteoarthritis cohort.
AB  - OBJECTIVE: To identify and validate previously established phenotypes of knee
      osteoarthritis (OA) based on similarities in clinical patient characteristics.
      METHODS: Knee OA patients (N = 551) from the Amsterdam OA (AMS-OA) cohort
      provided data. Four clinical patient characteristics were assessed: upper leg
      muscle strength, body mass index (BMI), radiographic severity (Kellgren/Lawrence
      [KL] grade), and depressive mood (the Hospital Anxiety and Depression Scale
      [HADS] questionnaire). Cluster analysis was performed to identify the optimal
      number of phenotypes. Differences in clinical characteristics between the
      phenotypes were analyzed with ANOVA. RESULTS: Cluster analysis identified five
      phenotypes of knee OA patients: "minimal joint disease phenotype", "strong muscle
      strength phenotype", "severe radiographic OA phenotype", "obese phenotype", and
      "depressive mood phenotype". CONCLUSIONS: Among patients with knee OA, five
      phenotypes were identified based on four clinical characteristics. To a high
      degree, the results are a replication of earlier findings in the OA Initiative,
      indicating that these five phenotypes seem a stable, valid, and clinically
      relevant finding.

PMID- 25596319
TI  - Peripheral and central effects of repeated social defeat stress: monocyte
      trafficking, microglial activation, and anxiety.
AB  - The development and exacerbation of depression and anxiety are associated with
      exposure to repeated psychosocial stress. Stress is known to affect the
      bidirectional communication between the nervous and immune systems leading to
      elevated levels of stress mediators including glucocorticoids (GCs) and
      catecholamines and increased trafficking of proinflammatory immune cells. Animal
      models, like the repeated social defeat (RSD) paradigm, were developed to explore
      this connection between stress and affective disorders. RSD induces activation of
      the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA)
      axis activation, increases bone marrow production and egress of primed, GC
      insensitive monocytes, and stimulates the trafficking of these cells to tissues
      including the spleen, lung, and brain. Recently, the observation that these
      monocytes have the ability to traffic to the brain perivascular spaces and
      parenchyma have provided mechanisms by which these peripheral cells may
      contribute to the prolonged anxiety-like behavior associated with RSD. The data
      that have been amassed from the RSD paradigm and others recapitulate many of the
      behavioral and immunological phenotypes associated with human anxiety disorders
      and may serve to elucidate potential avenues of treatment for these disorders.
      Here, we will discuss novel and key data that will present an overview of the
      neuroendocrine, immunological and behavioral responses to social stressors. 

PMID- 25596323
TI  - The arthropathic and functional impairment features of adult Kashin-Beck disease
      patients in Aba Tibetan area in China.
AB  - OBJECT: The purpose of the study was to analyze the features of arthropathic
      changes and functional impairments as well as the correlations between them for
      adult patients suffered with Kashin-Beck disease (KBD) in Aba Tibetan area of
      Sichuan Province, China. METHOD: Nine hundred and eighty-nine adult KBD patients
      in Aba KBD prevalence area were investigated. The arthropathic changes including
      arthritic pain (evaluated by visual analog pain score (VAS)), deformity, limited
      range of joint motion (ROM), as well as daily living and working function were
      examined, evaluated and analyzed. RESULTS: Ninety-two percent of patients
      suffered with multiple affected joints in both upper and lower extremities. The
      most frequently affected joints were knee (86.1%) and hand (77.2%). The most
      painful joints were knee (VAS 7.1 +/- 1.9) and elbow (VAS 6.8 +/- 2.1). Joint
      deformities most frequently represented as enlargement of interphalangeal joints
      (93.2%). Limitation of ROM occurred most frequently in hand (76.7%) and elbow
      (38.4%). Multiple linear regression analysis revealed that only joint pain
      (regression coefficient: -0.504, 95% confidence interval (CI): -0.820-0.188, P <
      0.001) and ROM (regression coefficient: 0.017, 95% CI: 0.011-0.024, P < 0.001)
      were independent risk factors affecting daily living and working function.
      CONCLUSION: Most adult patients suffered with multiple affected joints in both
      upper and lower limbs. The elbow, hand and knee were the most frequently and
      severely affected joints. The pain and limited ROM were the independent risk
      factors of daily living and working function.

PMID- 25596324
TI  - Retinal arteriolar narrowing and incidence of knee replacement for
      osteoarthritis: a prospective cohort study.
AB  - OBJECTIVES: The role of the microcirculation in the pathogenesis of
      osteoarthritis (OA) remains unclear. This prospective cohort study examined the
      association between retinal vascular calibre and incidence of knee replacement
      for OA. DESIGN: 1838 participants of the Australian Diabetes, Obesity and
      Lifestyle (AusDiab) Study had retinal vascular calibre measured using a
      nonmydriatic digital fundus camera in 1999-2000 and were aged >= 40 years at
      joint replacement data collection commencement. The incidence of knee replacement
      for OA during 2002-2011 was determined by linking cohort records to the
      Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR).
      RESULTS: 77 participants underwent knee replacement for OA. They had narrower
      retinal arteriolar calibre compared with those without knee replacement (166.1 +/
      24.8 MUm vs 174.3 +/- 24.5 MUm, P = 0.004). For every one standard deviation
      reduction in retinal arteriolar calibre, the incidence of knee replacement
      increased by 25% (HR 1.25, 95% confidence interval (CI) 1.00-1.56). Participants
      in the narrower two-thirds of arteriolar calibre had twice the risk of knee
      replacement compared with those in the widest one-third (HR 2.00, 95% CI 1.07
      3.74, P = 0.03) after adjustment for sex, body mass index (BMI), physical
      activity and HbA1c. There was no association for retinal venular calibre.
      CONCLUSIONS: Retinal arteriolar narrowing is associated with increased risk of
      knee replacement for OA suggesting that further work is warranted to determine
      the role of the microcirculation in the pathogenesis of knee OA.

PMID- 25596325
TI  - Specific aptamer-conjugated mesoporous silica-carbon nanoparticles for HER2
      targeted chemo-photothermal combined therapy.
AB  - Tumor-specific therapeutic platforms designed for combined tumor therapy has
      recently received wide attention. In this work, a new HB5 aptamer-functionalized
      mesoporous silica-carbon based doxorubicin (DOX)-loaded system (MSCN-PEG-HB5/DOX)
      was successfully constructed and characterized for chemo-photothermal combined
      therapy of human epithelial growth factor receptor 2 (HER2)-positive breast
      cancer cells. The in vitro release result showed that MSCN-PEG-HB5/DOX exhibited
      pH-sensitive and NIR-triggered release manner. HB5-modified nanoparticles showed
      significant higher cellular uptake in HER2-positive breast cancer cells (SK-BR-3)
      but not in normal breast epithelial cells (MCF-10A), compared to unmodified
      counterparts. The intracellular uptake of functional nanoparticles was mainly
      based on the receptor-mediated mechanism which was energy-dependent. Cytotoxicity
      experiments demonstrated that combined therapy induced highest cell killing
      effect compared to chemotherapy and photothermal therapy alone. The combination
      index (CI) was 0.253 indicating the synergistic effect of chemotherapy and
      photothermal therapy. These findings suggested that MSCN-PEG-HB5/DOX was a
      potential chemo-photothermal therapeutic platform targeting to HER2-positive
      breast cancers. 

PMID- 25596328
TI  - Steroid promiscuity: Diversity of enzyme action. Preface.
AB  - This Special Issue on the topic of Steroid and Sterol Signaling: Promiscuity and
      Diversity, dwells on the growing realization that the 'one ligand, one binding
      site' and 'one enzyme, one reaction' concepts are out of date. Focusing on
      cytochromes P450 (CYP), hydroxysteroid dehydrogenases (HSDs), and related
      enzymes, the Special Issue highlights that a single enzyme can bind to diverse
      substrates, and in different conformations, and can catalyze multiple different
      conversions (and in different directions), thereby, generating an unexpectedly
      wide spectrum of ligands that can have subtly different biological actions. This
      article is part of a Special Issue entitled 'Steroid/Sterol Signaling' . 

PMID- 25596326
TI  - Multivalent display of pendant pro-apoptotic peptides increases cytotoxic
      activity.
AB  - Several cationic antimicrobial peptides have been investigated as potential anti
      cancer drugs due to their demonstrated selective toxicity towards cancer cells
      relative to normal cells. For example, intracellular delivery of KLA, a pro
      apoptotic peptide, results in toxicity against a variety of cancer cell lines;
      however, the relatively low activity and small size lead to rapid renal excretion
      when applied in vivo, limiting its therapeutic potential. In this work, apoptotic
      peptide-polymer hybrid materials were developed to increase apoptotic peptide
      activity via multivalent display. Multivalent peptide materials were prepared
      with comb-like structure by RAFT copolymerization of peptide macromonomers with N
      (2-hydroxypropyl) methacrylamide (HPMA). Polymers displayed a GKRK peptide
      sequence for targeting p32, a protein often overexpressed on the surface of
      cancer cells, either fused with or as a comonomer to a KLA macromonomer. In three
      tested cancer cell lines, apoptotic polymers were significantly more cytotoxic
      than free peptides as evidenced by an order of magnitude decrease in IC50 values
      for the polymers compared to free peptide. The uptake efficiency and
      intracellular trafficking of one polymer construct was determined by
      radiolabeling and subcellular fractionation. Despite their more potent cytotoxic
      profile, polymeric KLA constructs have poor cellular uptake efficiency (<1%). A
      significant fraction (20%) of internalized constructs localize with intact
      mitochondrial fractions. In an effort to increase cellular uptake, polymer amines
      were converted to guanidines by reaction with O-methylisourea. Guanidinylated
      polymers disrupted function of isolated mitochondria more than their lysine-based
      analogs, but overall toxicity was decreased, likely due to inefficient
      mitochondrial trafficking. Thus, while multivalent KLA polymers are more potent
      than KLA peptides, these materials can be substantially improved by designing
      next generation materials with improved cellular internalization and
      mitochondrial targeting efficiency. 

PMID- 25596327
TI  - Molecular aspects of pancreatic beta cell failure and diabetes.

PMID- 25596329
TI  - Androgen correlates of male reproductive effort in wild male long-tailed macaques
      (Macaca fascicularis): A multi-level test of the challenge hypothesis.
AB  - The challenge hypothesis (Wingfield et al., 1990) has been broadly utilised as a
      conceptual framework to study male androgen correlates of reproductive challenges
      in mammals. These studies mainly assessed male androgen responsiveness to a
      general degree of challenge over extended periods of time. Short term co
      variation between the socio-sexual challenging context and androgen levels
      remains, however, largely understudied. We thus aim at providing a multi-level
      test of the challenge hypothesis by investigating the inter- and intra-individual
      variations in faecal androgen excretion associated to 1) breeding seasonality, 2)
      dominance rank, 3) mate-guarding activity and 4) value of the guarded female. We
      studied long-tailed macaques, a species in which males engage in highly
      challenging monopolisation of females over discreet periods of time. This
      particularity allows testing specifically the predicted increase from level B to
      level C in the challenge hypothesis. The study was carried out during two
      reproductive seasons on three groups of wild long-tailed macaques. We combined
      behavioural observations and non-invasive measurements of faecal androgen
      metabolite (fAM) levels. We found that, as predicted by the challenge hypothesis,
      male long-tailed macaques respond not only to seasonal but also to short term
      reproductive challenges by adapting their androgen levels. First, males exhibited
      a seasonal rise in fAM levels during the mating period which may be triggered by
      fruit availability as shown by our phenological data. Second, males had increased
      androgen levels when mate-guarding females and, across mate-guarding periods,
      males had higher fAM levels when monopolising high-ranking parous females than
      when monopolising low-ranking ones. Finally, high-ranking males had higher fAM
      levels than low-ranking males year round. Our study confirms that, in species
      with a high degree of female monopolisability, androgen may be an important
      physiological fitness enhancing tool for males by increasing female
      monopolisation efficiency (in particular with highly valuable females) and
      helping males to respond to rank take-over challenges. 

PMID- 25596330
TI  - A new neurometric dissection of the area-under-curve-associated jiggle of the
      motor evoked potential induced by transcranial magnetic stimulation.
AB  - OBJECTIVE: The jiggle of the motor evoked potential (MEP) induced by transcranial
      magnetic stimulation (TMS) depends on a number of factors including the
      assessment of this stochastic signal by the method known as area under curve
      (AUC). We aim to ascertain the MEP findings assessed by the AUC method obtained
      from individuals affected by lesions at different levels of the neuroaxis.
      METHODS: We systematically search and critically appraise the scientific reports
      publishing on the MEP obtained from individuals with hypo- or hyperkinetic
      disorders of the neural system, and dissect the neurophysical assessment of the
      obtained data. To accomplish this, we used the instruments named to as U-Pen
      Instrument for Neurometric Evaluation Uncommonly and Rarely Obtained from
      NeuroSignals 1.0 (UPINEURON 1.0), and the Quality of Assessment Statistics Index
      (QuASI). RESULTS: The MEP differences found by the classical peak-to-peak method
      decreased or disappeared when the AUC was used. The opposite was also true
      (Kappa=<0.00). The internal consistency of the UPINEURON was 0.88. The mean of
      the UPINEURON 1.0 indicator was 34.8 (range=16-50), and the mean of the QuASI
      scores was 56.5 (range 30-80). Spearman correlation between UPINEURON 1.0 and
      QuASI was 0.513. CONCLUSIONS: The MEP jiggle found in individuals with disordered
      neural function is not a "minor" factor; it is beyond the underlying neural
      condition, sample size, type of coils, and number of trials, among other
      variables. The use of the novel indicators introduced in this investigation will
      help to improve the analysis of the AUC of neural signals. They may also lead to
      the reconsideration of current practices.

PMID- 25596332
TI  - Age-at-onset and comorbidity may separate depressive disorder subtypes along a
      descending gradient of bipolar propensity.
AB  - Depressive illnesses with subthreshold bipolar features are still misdiagnosed as
      unipolar. The goal of this study was to identify depressive disorder subtypes at
      risk for bipolarity. Four hundred ninety three major depressive patients were
      submitted to a cluster analysis on the basis of affective illness history and
      symptoms of the current episode. Seven clusters were identified which were
      regrouped into three age-at-onset subgroups; subgroups were further
      differentiated into subtypes according to predominant comorbidities. The latter
      were found to precede the occurrence of the related depressive disorder subtypes,
      decrease their age-at-onset, and increase their risk of belonging to the bipolar
      spectrum: the earlier the comorbidity, the higher the bipolar propensity was.
      This is likely to have implications for the diagnosis, natural history, as well
      as prophylaxis of bipolar disorders. 

PMID- 25596331
TI  - Acute reversal of phospholamban inhibition facilitates the rhythmic whole-cell
      propagating calcium waves in isolated ventricular myocytes.
AB  - Phospholamban (PLB) inhibits the activity of cardiac sarcoplasmic reticulum (SR)
      Ca(2+)-ATPase (SERCA2a). Phosphorylation of PLB during sympathetic activation
      reverses SERCA2a inhibition, increasing SR Ca(2+) uptake. However, sympathetic
      activation also modulates multiple other intracellular targets in ventricular
      myocytes (VMs), making it impossible to determine the specific effects of the
      reversal of PLB inhibition on the spontaneous SR Ca(2+) release. Therefore, it
      remains unclear how PLB regulates rhythmic activity in VMs. Here, we used the Fab
      fragment of 2D12, a monoclonal anti-PLB antibody, to test how acute reversal of
      PLB inhibition affects the spontaneous SR Ca(2+) release in normal VMs. Ca(2+)
      sparks and spontaneous Ca(2+) waves (SCWs) were recorded in the line-scan mode of
      confocal microscopy using the Ca(2+) fluorescent dye Fluo-4 in isolated
      permeabilized mouse VMs. Fab, which reverses PLB inhibition, significantly
      increased the frequency, amplitude, and spatial/temporal spread of Ca(2+) sparks
      in VMs exposed to 50 nM free [Ca(2+)]. At physiological diastolic free [Ca(2+)]
      (100-200 nM), Fab facilitated the formation of whole-cell propagating SCWs. At
      higher free [Ca(2+)], Fab increased the frequency and velocity, but decreased the
      decay time of the SCWs. cAMP had little additional effect on the frequency or
      morphology of Ca(2+) sparks or SCWs after Fab addition. These findings were
      complemented by computer simulations. In conclusion, acute reversal of PLB
      inhibition alone significantly increased the spontaneous SR Ca(2+) release,
      leading to the facilitation and organization of whole-cell propagating SCWs in
      normal VMs. PLB thus plays a key role in subcellular Ca(2+) dynamics and rhythmic
      activity of VMs.

PMID- 25596334
TI  - Characterization of ampicillin-stressed proteomics and development of a direct
      method for detecting drug-binding proteins in Edwardsiella tarda.
AB  - Antibiotic-resistant Edwardsiella tarda poses a severe challenge to aquaculture.
      An understanding for antibiotic-resistant mechanisms is crucial to control the
      disease. The present study characterizes E. tarda ampicillin-stressed proteome
      and shows the importance of energy metabolism including the TCA cycle and
      glycolysis/gluconeogenesis in the antibiotic resistance. Further combination with
      antibiotic measurement develops a new method for identification of antibiotic
      binding proteins out of differential abundances of proteins and results in
      determination of ETAE_0175 and ETAE_3367 as ampicillin-binding proteins in E.
      tarda. Genes of the two proteins are cloned and recombinant proteins are purified
      for validation of antibiotic-binding capability. Results show that higher binding
      capability is detected in ETAE_3367 than ETAE_0175. Out of the two proteins,
      ETAE_3367 is first reported here to be an antibiotic-binding protein, while
      ETAE_0175 homology in other bacteria has been shown to bind with other
      antibiotics. Bioinformatics analysis shows that ETAE_3367 may closely interact
      with aceF and sucA belonging to the TCA cycle and glycolysis/gluconeogenesis,
      respectively. These results indicate that energy metabolism contributes to
      ampicillin resistance in E. tarda and a new method to identify antibiotic-binding
      proteins is developed. These findings highlight the way to an understanding of
      antibiotic-resistant mechanisms in content of antibiotic-binding proteins.
      BIOLOGICAL SIGNIFICANCE: Our data characterizes Edwardsiella tarda ampicillin
      stressed proteome and shows the importance of energy metabolism including the TCA
      cycle and glycolysis/gluconeogenesis in the antibiotic resistance. Furthermore, a
      new method based 2-DE proteomics is developed for identification of antibiotic
      binding proteins, which results in determination of ETAE_0175 and ETAE_3367 as
      ampicillin-binding proteins in E. tarda. ETAE_3367 is closely interacted with
      proteins of the TCA cycle and glycolysis/gluconeogenesis, suggesting the drug
      resistant mechanism.

PMID- 25596333
TI  - Infant visual attention and object recognition.
AB  - This paper explores the role visual attention plays in the recognition of objects
      in infancy. Research and theory on the development of infant attention and
      recognition memory are reviewed in three major sections. The first section
      reviews some of the major findings and theory emerging from a rich tradition of
      behavioral research utilizing preferential looking tasks to examine visual
      attention and recognition memory in infancy. The second section examines research
      utilizing neural measures of attention and object recognition in infancy as well
      as research on brain-behavior relations in the early development of attention and
      recognition memory. The third section addresses potential areas of the brain
      involved in infant object recognition and visual attention. An integrated
      synthesis of some of the existing models of the development of visual attention
      is presented which may account for the observed changes in behavioral and neural
      measures of visual attention and object recognition that occur across infancy. 

PMID- 25596335
TI  - The many faces of cell adhesion during Drosophila muscle development.
AB  - Muscle development involves a series of morphogenetic events including cell
      fusion, migration and epidermal attachment. At various points in this complex
      developmental program, regulation of muscle-muscle and muscle-epidermal adhesion
      is crucial. One of the best-characterised adhesion events is the formation of
      stable, integrin-based adhesions at the attachment sites formed between the ends
      of muscles and epidermal cells, but other adhesion mechanisms are involved in
      earlier stages. Here we review recent work from Drosophila on the role of
      adhesion during muscle development, situating integrin function within the wider
      developmental program. 

PMID- 25596336
TI  - Lizard tail regeneration: regulation of two distinct cartilage regions by Indian
      hedgehog.
AB  - Lizards capable of caudal autotomy exhibit the remarkable ability to "drop" and
      then regenerate their tails. However, the regenerated lizard tail (RLT) is known
      as an "imperfect replicate" due to several key anatomical differences compared to
      the original tail. Most striking of these "imperfections" concerns the skeleton;
      instead of the vertebrae of the original tail, the skeleton of the RLT takes the
      form of an unsegmented cartilage tube (CT). Here we have performed the first
      detailed staging of skeletal development of the RLT CT, identifying two distinct
      mineralization events. CTs isolated from RLTs of various ages were analyzed by
      micro-computed tomography to characterize mineralization, and to correlate
      skeletal development with expression of endochondral ossification markers
      evaluated by histology and immunohistochemistry. During early tail regeneration,
      shortly after CT formation, the extreme proximal CT in direct contact with the
      most terminal vertebra of the original tail develops a growth plate-like region
      that undergoes endochondral ossification. Proximal CT chondrocytes enlarge,
      express hypertrophic markers, including Indian hedgehog (Ihh), apoptose, and are
      replaced by bone. During later stages of tail regeneration, the distal CT
      mineralizes without endochondral ossification. The sub-perichondrium of the
      distal CT expresses Ihh, and the perichondrium directly calcifies without
      cartilage growth plate formation. The calcified CT perichondrium also contains a
      population of stem/progenitor cells that forms new cartilage in response to TGF
      beta stimulation. Treatment with the Ihh inhibitor cyclopamine inhibited both
      proximal CT ossification and distal CT calcification. Thus, while the two
      mineralization events are spatially, temporally, and mechanistically very
      different, they both involve Ihh. Taken together, these results suggest that Ihh
      regulates CT mineralization during two distinct stages of lizard tail
      regeneration. 

PMID- 25596337
TI  - Optimal isolation of mitochondria for proteomic analyses.
AB  - Considering the key role of mitochondria in cellular (dys)functions, we compared
      a standard isolation protocol, followed by lysis in urea/detergent buffer, with a
      commercially available isolation buffer that rapidly yields a mitochondrial
      protein fraction. The standard protocol yielded significantly better overall
      resolution and coverage of both the soluble and membrane mitochondrial proteomes;
      although the kit was faster, it resulted in recovery of only approximately 56% of
      the detectable proteome. The quality of "omic" analysis depends on sample
      handling; for large-scale protein studies, well-resolved proteomes are highly
      dependent on the purity of starting material and the rigor of the extraction
      protocol. 

PMID- 25596338
TI  - iDNA-Methyl: identifying DNA methylation sites via pseudo trinucleotide
      composition.
AB  - Predominantly occurring on cytosine, DNA methylation is a process by which cells
      can modify their DNAs to change the expression of gene products. It plays very
      important roles in life development but also in forming nearly all types of
      cancer. Therefore, knowledge of DNA methylation sites is significant for both
      basic research and drug development. Given an uncharacterized DNA sequence
      containing many cytosine residues, which one can be methylated and which one
      cannot? With the avalanche of DNA sequences generated during the postgenomic age,
      it is highly desired to develop computational methods for accurately identifying
      the methylation sites in DNA. Using the trinucleotide composition, pseudo amino
      acid components, and a dataset-optimizing technique, we have developed a new
      predictor called "iDNA-Methyl" that has achieved remarkably higher success rates
      in identifying the DNA methylation sites than the existing predictors. A user
      friendly web-server for the new predictor has been established at http://www.jci
      bioinfo.cn/iDNA-Methyl, where users can easily get their desired results. We
      anticipate that the web-server predictor will become a very useful high
      throughput tool for basic research and drug development and that the novel
      approach and technique can also be used to investigate many other DNA-related
      problems and genome analysis. 

PMID- 25596339
TI  - The effect of 4alpha,5alpha-epoxy-10alpha,14-dihydro-inuviscolide, a novel
      immunosuppressant isolated from Carpesium abrotanoides, on the cytokine profile
      in vitro and in vivo.
AB  - The plant Carpesium abrotanoides (CA) is used in Asian herbal medicines as an
      insecticide and to treat bruises. However, the effect of single compounds from CA
      blooms and the mechanism of its immunosuppressive effect remain poorly
      understood. The aim of this study was to investigate the mechanism of the
      immunosuppressive effect in the three kinds of immune cells, and the
      immunosuppressive effect of CA bloom extract (CAE) in acute inflammation models
      (LPS and ConA-induced inflammation). Interleukin-6, IL-4, IL-13, IFNgamma, and IL
      10-but not TNFalpha-were significantly reduced in a dose-dependent manner by
      4alpha,5alpha-epoxy-10alpha,14-dihydro-inuviscolide (INV). Furthermore, INV
      inhibited NF-kappaB transcriptional activation and IL-10 promoter activity in the
      same manner as for Bay11. Meanwhile, treatment with dexamethasone reduced the
      levels of IFNgamma, but not IL-10, and resulted in no change in NF-kappaB
      transcriptional activation or the IL-10 promoter. INV did not affect PMA-induced
      IkappaB kinase complex phosphorylation, IkappaB degradation, or MAPK and the
      nuclear translocation of p65, as with DEX. The in vivo, CAE has an
      immunosuppressive effect on the LPS-induced inflammation response model by
      inhibiting the plasma level of IFNgamma and IL-6 levels. CAE treatment also tends
      to attenuate the plasma level of IFNgamma, IL-4, and IL-6 in ConA-induced
      inflammation. These findings indicate that INV causes the reduction of the
      cytokine profile by blocking the NF-kappaB transcription factor activation and
      the molecular mechanism by which INV operates could provide new insights into the
      unique mechanisms responsible for NF-kappaB inhibition, in contrast to
      established immunosuppressants, as a therapeutic agent for immunopathological
      treatment. 

PMID- 25596340
TI  - Combining magnetic nanoparticles with cell derived microvesicles for drug loading
      and targeting.
AB  - Inspired by microvesicle-mediated intercellular communication, we propose a
      hybrid vector for magnetic drug delivery. It consists of macrophage-derived
      microvesicles engineered to enclose different therapeutic agents together with
      iron oxide nanoparticles. Here, we investigated in vitro how magnetic
      nanoparticles may influence the vector effectiveness in terms of drug uptake and
      targeting. Human macrophages were loaded with iron oxide nanoparticles and
      different therapeutic agents: a chemotherapeutic agent (doxorubicin), tissue
      plasminogen activator (t-PA) and two photosensitizers (disulfonated tetraphenyl
      chlorin-TPCS2a and 5,10,15,20-tetra(m-hydroxyphenyl)chlorin-mTHPC). The hybrid
      cell microvesicles were magnetically responsive, readily manipulated by magnetic
      forces and MRI-detectable. Using photosensitizer-loaded vesicles, we showed that
      the uptake of microvesicles by cancer cells could be kinetically modulated and
      spatially controlled under magnetic field and that cancer cell death was enhanced
      by the magnetic targeting. From the clinical editor: In this article, the authors
      devised a biogenic method using macrophages to produce microvesicles containing
      both iron oxide and chemotherapeutic agents. They showed that the microvesicles
      could be manipulated by magnetic force for targeting and subsequent delivery of
      the drug payload against cancer cells. This smart method could provide a novel
      way for future fight against cancer.

PMID- 25596341
TI  - Highly aligned nanocomposite scaffolds by electrospinning and electrospraying for
      neural tissue regeneration.
AB  - Neural tissue engineering offers a promising avenue for repairing neural
      injuries. Advancement in nanotechnology and neural scaffold manufacturing
      strategies has shed light on this field into a new era. In this study, a novel
      tissue engineered scaffold, which possesses highly aligned poly-epsilon
      caprolactone microfibrous framework and adjustable bioactive factor embedded poly
      (d, l-lactide-co-glycolide) core-shell nanospheres, was fabricated by combining
      electrospinning and electrospraying techniques. The fabricated nanocomposite
      scaffold has cell favorable nanostructured feature and improved hydrophilic
      surface property. More importantly, by incorporating core-shell nanospheres into
      microfibrous scaffold, a sustained bioactive factor release was achieved. Results
      show rat pheochromocytoma (PC-12) cell proliferation was significantly promoted
      on the nanocomposite scaffold. In addition, confocal microscope images
      illustrated that the highly aligned scaffold increased length of neurites and
      directed neurites extension along the fibers in both PC-12 and astrocyte cell
      lines, which indicates that the scaffold is promising for guiding neural tissue
      growth and regeneration. From the clinical editor: In an attempt to direct neural
      cell growth, biomimetic neural scaffold was produced by electrospinning
      integrated with co-axial electrospraying techniques. In-vitro data provided a
      framework for future designs for neuronal regeneration.

PMID- 25596342
TI  - The impairment of cholesterol metabolism in Huntington disease.
AB  - Huntington disease (HD), an autosomal dominant neurodegenerative disorder caused
      by an abnormal expansion of CAG trinucleotide repeat in the Huntingtin (HTT)
      gene, is characterized by extensive neurodegeneration of striatum and cortex and
      severe diffuse atrophy at MRI. The expression of genes involved in the
      cholesterol biosynthetic pathway and the amount of cholesterol, lanosterol,
      lathosterol and 24S-hydroxycholesterol were reduced in murine models of HD. In
      case of HD-patients, the decrease of plasma 24OHC follows disease progression
      proportionally to motor and neuropsychiatric dysfunction and MRI brain atrophy,
      together with lanosterol and lathosterol (markers of cholesterol synthesis), and
      27-hydroxycholesterol. A significant reduction of total plasma cholesterol was
      observed only in advanced stages. It is likely that mutant HTT decreases the
      maturation of SREBP and the up-regulation LXR and LXR-targeted genes (SREBP,
      ABCG1 and ABCG4, HMGCoA reductase, ApoE) resulting into a lower synthesis and
      transport of cholesterol from astrocytes to neurons via ApoE. In primary
      oligodendrocytes, mutant HTT inhibited the regulatory effect of PGC1alpha on
      cholesterol metabolism and on the expression of MBP. HTT seems to play a
      regulatory role in lipid metabolism. The impairment of the cholesterol metabolism
      was found to be proportional to the CAG repeat length and to the load of mutant
      HTT. A dysregulation on PGC1alpha and mitochondria dysfunction may be involved in
      an overall reduction of acetyl-CoA and ATP synthesis, contributing to the
      cerebral and whole body cholesterol impairment. This article is part of a Special
      Issue entitled Brain Lipids. 

PMID- 25596343
TI  - Glycerophosphodiesterase GDE4 as a novel lysophospholipase D: a possible
      involvement in bioactive N-acylethanolamine biosynthesis.
AB  - Bioactive N-acylethanolamines include anti-inflammatory palmitoylethanolamide,
      anorexic oleoylethanolamide, and an endocannabinoid arachidonoylethanolamide
      (anandamide). In animal tissues, these molecules are biosynthesized from N
      acylethanolamine phospholipids directly by phospholipase D-type enzyme or through
      multi-step routes via N-acylethanolamine lysophospholipids. We previously found
      that mouse brain has a lysophospholipase D (lysoPLD) activity hydrolyzing N
      acylethanolamine lysophospholipids to N-acylethanolamines and that this activity
      could be partially attributed to glycerophosphodiesterase (GDE) 1. In the present
      study, we examined catalytic properties of GDE4, another member of the GDE
      family. When overexpressed in HEK293 cells, murine GDE4 mostly resided in the
      membrane fraction. Purified GDE4 showed lysoPLD activity toward various
      lysophospholipids, including N-acylethanolamine lysophospholipids as well as
      lysophosphatidylethanolamine and lysophosphatidylcholine. When HEK293 cells were
      metabolically labeled with N-[(14)C]palmitoylethanolamine lysophospholipid, the
      transient expression of GDE4 increased the [(14)C]palmitoylethanolamide level,
      while the knockdown of endogenous GDE4 decreased this level. These results
      suggested that GDE4 functions as an N-acylethanolamine-generating lysoPLD in
      living cells. Moreover, the expression of GDE4 increased most species of
      lysophosphatidic acid (LPA), which can be produced from various lysophospholipids
      by the lysoPLD activity of GDE4. GDE4 mRNA was widely distributed among mouse
      tissues including brain, stomach, ileum, colon, and testis. In conclusion, GDE4
      may act as a lysoPLD, which is involved in the generation of N-acylethanolamines
      and LPA. 

PMID- 25596344
TI  - Flourishing in people with depressive symptomatology increases with Acceptance
      and Commitment Therapy. Post-hoc analyses of a randomized controlled trial.
AB  - Mental health is more than the absence of mental illness. Rather, both well-being
      (positive mental health) and mental illness are actually two related continua,
      with higher levels of well-being defined as "flourishing." This two-continua
      model and existing studies about the impact of flourishing on psychopathology
      underscore the need for interventions that enhance flourishing and well-being.
      Acceptance and Commitment Therapy (ACT) is a model of cognitive behavioral
      therapy that aims not only to reduce psychopathology but also to promote
      flourishing as well. This is the first study to evaluate the impact of ACT on
      flourishing. A post-analysis was conducted on an earlier randomized controlled
      trial of a sample of adults with depressive symptomatology who participated in a
      guided self-help ACT intervention. This post-analysis showed a 5%-28% increase of
      flourishing by the participants. In addition, the effects on flourishing were
      maintained at the three-month follow-up. When compared to participants in a
      control group, the flourishing of the ACT-trained participants increased from 5%
      to about 14% after nine weeks. In addition to levels of positive mental health at
      baseline, an increase of psychological flexibility during the intervention was a
      significant predictor of flourishing at the three-month follow-up. 

PMID- 25596345
TI  - Heat shock transcription factors expression during fruit development and under
      hot air stress in Ponkan (Citrus reticulata Blanco cv. Ponkan) fruit.
AB  - Heat shock transcription factors (Hsfs) play a role in plant responses to stress.
      Citrus is an economically important fruit whose genome has been fully sequenced.
      So far, no detailed characterization of the Hsf gene family is available for
      citrus. A genome-wide analysis was carried out in Citrus clementina to identify
      Hsf genes, named CcHsfs. Eighteen CcHsfs were identified and classified into
      three main clades (clades A, B and C) according to the structural characteristics
      and the phylogenetic comparison with Arabidopsis and tomato. MEME motif analysis
      highlighted the conserved DBD and HR-A/B domains, which were similar to Hsf
      protein structures in other species. Gene expression analysis in Ponkan (Citrus
      reticulata Blanco cv. Ponkan) fruit identified 14 Hsf genes, named CrHsf, as
      important candidates for a role in fruit development and ripening, and showed
      seven genes to be expressed in response to hot air stress. CrHsfB2a and CrHsfB5
      were considered to be important regulators of citrate content and showed
      variation in both developmentally-related and hot air-triggered citrate
      degradation processes. In summary, the data obtained from this investigation
      provides the basis for further study to dissect Hsf function during fruit
      development as well as in response to heat stress and also emphasizes the
      potential importance of CrHsfs in regulation of citrate metabolism in citrus
      fruit. 

PMID- 25596346
TI  - Association between VEGF -634G/C polymorphism and susceptibility to autoimmune
      diseases: a meta-analysis.
AB  - The role of VEGF -634G/C polymorphism has been involved in the investigations of
      susceptibility to autoimmune diseases, but the conclusion remains controversial.
      Here, we have performed a meta-analysis to clarify the relationship between them.
      All relevant articles updating to August 2013 were searched in PubMed and EMBASE.
      Crude odds ratios (ORs) with 95% confidence intervals (CIs) based on the
      available articles were calculated. A total of 24 independent studies associated
      with autoimmune disease were analyzed in our research. The results show that VEGF
      -634G/C polymorphism was associated with susceptibility to autoimmune disease in
      Asian population (C vs. G: OR=0.88, 95% CI: 0.80-0.96, P=0.543; CC vs. GG:
      OR=0.77, 95% CI: 0.63-0.93, P=0.787; CC+GC vs. GG: OR=0.80, 95% CI: 0.67-0.96,
      P=0.080 by random effects model). Nevertheless, no significant associations were
      found in total population or in other stratified groups. In the current meta
      analysis, we reveal a significant association between VEGF -634G/C polymorphism
      and susceptibility to autoimmune diseases in Asian population. 

PMID- 25596347
TI  - DNA barcoding for species identification from dried and powdered plant parts: a
      case study with authentication of the raw drug market samples of Sida cordifolia.
AB  - The majority of the plant materials used in herbal medicine is procured from the
      markets in the form of dried or powdered plant parts. It is essential to use
      authentic plant materials to derive the benefits of herbal medicine. However,
      establishing the identity of these plant materials by conventional taxonomy is
      extremely difficult. Here we report a case study in which the species
      identification of the market samples of Sida cordifolia was done by DNA
      barcoding. As a prelude to species identification by DNA barcoding, 13 species of
      Sida were collected, and a reference DNA barcode library was developed using
      rbcL, matK, psbA-trnH and ITS2 markers. Based on the intra-species and inter
      species divergence observed, psbA-trnH and ITS2 were found to be the best two
      marker combination for species identification of the market samples. The study
      showed that none of the market samples belonged to the authentic species, S.
      cordifolia. Seventy-six per cent of the market samples belonged to other species
      of Sida. The predominant one was Sida acuta (36%) followed by S. spinosa (20%),
      S. alnifolia (12%), S. scabrida (4%) and S. ravii (4%). Such substitutions may
      not only fail to give the expected therapeutic effect, but may also give
      undesirable effects as in case of S. acuta which contains a 6-fold higher amount
      of ephedrine compared to the roots of S. cordifolia. The remaining 24% of the
      samples were from other genera such as Abutilon sp. (8%), Ixonanthes sp.,
      Terminalia sp., Fagonia sp., and Tephrosia sp. (4% each). This observation is in
      contrast to the belief that medicinal plants are generally substituted or
      adulterated with closely related species. The current study strongly suggests
      that the raw drug market samples of herbal medicines need to be properly
      authenticated before use, and DNA barcoding has been found to be suitable for
      this purpose.

PMID- 25596348
TI  - Rethinking transcription coupled DNA repair.
AB  - Nucleotide excision repair (NER) is an evolutionarily conserved, multistep
      process that can detect a wide variety of DNA lesions. Transcription coupled
      repair (TCR) is a subpathway of NER that repairs the transcribed DNA strand
      faster than the rest of the genome. RNA polymerase (RNAP) stalled at DNA lesions
      mediates the recruitment of NER enzymes to the damage site. In this review we
      focus on a newly identified bacterial TCR pathway in which the NER enzyme UvrD,
      in conjunction with NusA, plays a major role in initiating the repair process. We
      discuss the tradeoff between the new and conventional models of TCR, how and when
      each pathway operates to repair DNA damage, and the necessity of pervasive
      transcription in maintaining genome integrity.

PMID- 25596349
TI  - Characterising phosphorus and nitrate inputs to a rural river using high
      frequency concentration-flow relationships.
AB  - The total reactive phosphorus (TRP) and nitrate concentrations of the River
      Enborne, southern England, were monitored at hourly interval between January 2010
      and December 2011. The relationships between these high-frequency nutrient
      concentration signals and flow were used to infer changes in nutrient source and
      dynamics through the annual cycle and each individual storm event, by studying
      hysteresis patterns. TRP concentrations exhibited strong dilution patterns with
      increasing flow, and predominantly clockwise hysteresis through storm events.
      Despite the Enborne catchment being relatively rural for southern England, TRP
      inputs were dominated by constant, non-rain-related inputs from sewage treatment
      works (STW) for the majority of the year, producing the highest phosphorus
      concentrations through the spring-summer growing season. At higher river flows,
      the majority of the TRP load was derived from within-channel remobilisation of
      phosphorus from the bed sediment, much of which was also derived from STW inputs.
      Therefore, future phosphorus mitigation measures should focus on STW
      improvements. Agricultural diffuse TRP inputs were only evident during storms in
      the May of each year, probably relating to manure application to land. The
      nitrate concentration-flow relationship produced a series of dilution curves,
      indicating major inputs from groundwater and to a lesser extent STW. Significant
      diffuse agricultural inputs with anticlockwise hysteresis trajectories were
      observed during the first major storms of the winter period. The simultaneous
      investigation of high-frequency time series data, concentration-flow
      relationships and hysteresis behaviour through multiple storms for both
      phosphorus and nitrate offers a simple and innovative approach for providing new
      insights into nutrient sources and dynamics. 

PMID- 25596350
TI  - Tree species affect cation exchange capacity (CEC) and cation binding properties
      of organic matter in acid forest soils.
AB  - Soil organic matter (SOM) in forest soil is of major importance for cation
      binding and acid buffering, but its characteristics may differ among soils under
      different tree species. We investigated acidity, cation exchange properties and
      Al bonding to SOM in stands of Scots pine, pedunculate oak, Norway spruce,
      European beech and common hornbeam in southern Poland. The content of total
      carbon (Ct) was by far the major contributor to total cation exchange capacity
      (CECt) even in loamy soils and a strong relationship between Ct and CECt was
      found. The slope of the regression of CECt to Ct increased in the order
      hornbeam~oak<beech<spruce~pine, suggesting that the number of negatively charged
      sites of SOM at any value in the acid pH range was smallest for hornbeam and oak,
      and largest for spruce and pine soils. This was supported by the apparent
      dissociation constant (pKapp) values of SOM, which were largest in soils under
      oak. The maximum values of Al saturation were similar between the stands.
      However, maximum Al bonding to SOM occurred at higher pH values in soils under
      pine and spruce than under oak. Therefore, at any value in the acid pH range, the
      SOM in pine soil has less Al complexed and more adsorbed H+ than SOM from oak
      soils. Such differences in Al and H bonding are not only important for pH
      buffering and metal solubility controls, but also for stabilization of SOM via
      saturation of functional groups by Al and H.

PMID- 25596351
TI  - Assessment of a mussel as a metal bioindicator of coastal contamination:
      relationships between metal bioaccumulation and multiple biomarker responses.
AB  - This is the first study to use a multiple biomarker approach on the green-lipped
      mussel, Perna canaliculus to test its feasibility as a bioindicator of coastal
      metal contamination in New Zealand (NZ). Mussels were collected from six low
      intertidal sites varying in terms of anthropogenic impacts, within two regions
      (West Coast and Nelson) of the South Island of NZ. Trace elements, including
      arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn),
      were measured in the gills, digestive gland, foot and mantle, and in the surface
      sediments from where mussels were collected. Metal levels in the sediment were
      relatively low and there was only one site (Mapua, Nelson) where a metal (Ni)
      exceeded the Australian and New Zealand Interim Sediment Quality Guideline
      values. Metal levels in the digestive gland were generally higher than those from
      the other tissues. A variety of biomarkers were assessed to ascertain mussel
      health. Clearance rate, a physiological endpoint, correlated with metal level in
      the tissues, and along with scope for growth, was reduced in the most
      contaminated site. Metallothionein-like protein content and catalase activity in
      the digestive gland, and catalase activity and lipid peroxidation in the gill,
      were also correlated to metal accumulation. Although there were few regional
      differences, the sampling sites were clearly distinguishable based on the metal
      contamination profiles and biomarker responses. P. canaliculus appears to be a
      useful bioindicator species for coastal habitats subject to metal contamination.
      In this study tissue and whole organism responses provided insight into the
      biological stress responses of mussels to metal contaminants, indicating that
      such measurements could be a useful addition to biomonitoring programmes in NZ. 

PMID- 25596352
TI  - Biopharmaceutical and pharmacokinetic characterization of asiatic acid in
      Centella asiatica as determined by a sensitive and robust HPLC-MS method.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Asiatic acid is one of the main components in the
      herb Centella asiatica, which is a well-known herbal medicine for its excellent
      pharmacological effects. To enhance the development potentials of asiatic acid as
      a chemopreventative agent, there is a great need to further understand its
      biopharmaceutical and pharmacokinetic properties. The aim of this research is to
      clarify the mechanisms of absorption and metabolism of asiatic acid, and explore
      its biopharmaceutical and pharmacokinetic properties in rats by using a sensitive
      and robust HPLC-MS method. MATERIALS AND METHODS: Male Sprague-Dawley rats were
      randomly assigned to 2 groups and administered with asiatic acid by oral and
      intravenous administration. Plasma concentrations of asiatic acid were determined
      at designated points and main pharmacokinetic parameters were estimated. The
      absorption of asiatic acid was investigated by using Caco-2 cell line absorption
      model in vitro and rat intestinal perfusion model in situ. The metabolic rate of
      asiatic acid was investigated by incubating it in rat liver microsome system in
      vitro. In addition, the solubility of asiatic acid in aqueous solution was also
      determined by using HPLC-MS method. RESULTS: The absolute oral bioavailability of
      asiatic acid is 16.25%. It was found that the permeability of asiatic acid is
      more than 10(-5) in the Caco-2 cell monolayer and rat intestinal perfusion model,
      and its main absorption region is the jejunum in rats. The metabolic rate of
      asiatic acid in rat liver microsomes, t1/2, is 9.493min, which shows that asiatic
      acid can be metabolized rapidly. The solubility of aisiatic acid was 0.1583mgmL(
      1), and its poor solubility will result in low bioavailability. CONCLUSIONS: The
      asiatic acid in a variety of matrixes was analyzed by using a sensitive and
      specific HPLC-MS method, and its absolute oral bioavailability in rats was very
      low. Asiatic acid can be metabolized rapidly in rat liver microsomes, and has
      good permeability across Caco-2 monolayer cell and rat intestine perfusion. It
      can be deduced that the low bioavailability of asiatic acid results from poor
      solubility and rapid metabolism.

PMID- 25596353
TI  - Ethnopharmacological approach to the herbal medicines of the "Antidotes" in
      Nikolaos Myrepsos' Dynameron.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper focuses on the plants quoted in the
      recipes of the first chapter entitled "About the Antidotes" belonging to the
      first and largest section "Element Alpha" of Nikolaos Myrepsos' Dynameron, a
      medieval medical manuscript. Nikolaos Myrepsos was a Byzantine physician at the
      court of John III Doukas Vatatzes at Nicaea (13th century). He wrote in Greek a
      rich collection of 2667 recipes, the richest number known in late Byzantine era,
      conventionally known as Dynameron and divided into 24 sections, the "Elements".
      The only existing translation of this work is in Latin, released in 1549 in Basel
      by Leonhart Fuchs. Since no other translation has ever been made in any language,
      this work still remains poorly known. MATERIALS AND METHODS: Our primary source
      material was the codex written in 1339 and kept in the National Library of France
      (in Paris) under the number grec. 2243. For comparison, all the other codices,
      which contain the entire manuscript, have also been studied, namely the codices
      EBE 1478 (National Library of Greece, Athens), grec. 2237 and grec. 2238 (both in
      Paris), Lavra Epsilon 192 (Mont Athos, Monastery of Megisti Lavra), Barocci 171
      (Oxford) and Revilla 83 (Escorial). RESULTS: The exhaustive study of the "About
      the Antidotes" led us to the interpretation of 293 plant names among which we
      recognized 39 medicinal plants listed by the European Medicines Agency, (Herbal
      Medicines, www.ema.eu); the therapeutic indications of some of them provided by
      Myrepsos were similar or related to their current ones, as given in their
      monographs. The plants belong to various families of which the most frequent are:
      Apiaceae 10.6%; Lamiaceae 9.2%; Asteraceae 8.9%; Fabaceae 6.8% and Rosaceae 5.1%.
      The most frequently mentioned plants even under several different names are the
      following: Apium graveolens L., Crocus sativus L., Nardostachys jatamansi (D.
      Don) DC., Zingiber officinale Roscoe, Rosa centifolia L., Syzygium aromaticum
      (L.) Merr. & L.M. Perry, Papaver somniferum L., Costus sp., Petroselinum crispum
      (Mill.) Fuss, Anethum graveolens L., Foeniculum vulgare Mill., Daucus carota L.
      CONCLUSIONS: This research led us to the conclusion that the content of "About
      the Antidotes" is a valuable source for the study of recipes based mainly on
      medicinal plants, most of them inherited from classic ancient Greek and
      Hellenistic periods.

PMID- 25596354
TI  - Leaves of Phragmites australis as potential atmospheric biomonitors of Platinum
      Group Elements.
AB  - The increasing emissions of Platinum Group Elements (PGEs), namely Pt, Pd and Rh,
      may pose a significant risk to ecosystem processes and human health. A periodic
      assessment of PGEs distribution in the environment is thus of the utmost
      importance for the implementation of timely measures of mitigation. Although
      several studies have quantified PGEs in different life forms such as mammals,
      birds, fish, crustaceans, algae, mosses and even human beings, data about
      vascular plants need further surveys. This study aimed to test the suitability of
      the grass Phragmites australis (common reed) as a biomonitor of PGEs atmospheric
      pollution. The results showed that Pd and Pt concentrations in leaves are
      significantly higher in urban areas. In particular, Pd showed the highest range
      of values in line with current studies that consider palladium as the main
      element of traffic-related pollution. Overall, the leaves of Phragmites australis
      reflected the different gradient of PGEs emissions, and may thus be considered as
      potential biomonitors of atmospheric pollution. 

PMID- 25596356
TI  - Does treatment of asymptomatic, small renal calculi depend on the patient
      population?

PMID- 25596355
TI  - The impact of late, non-balanced bilingualism on cognitive performance.
AB  - We present a study examining cognitive functions in late non-balanced bilinguals
      with different levels of second language proficiency. We examined in two
      experiments a total of 193 mono- and bilingual university students. We assessed
      different aspects of attention (sustained, selective and attentional switching),
      verbal fluency (letter and category) as well as picture-word association as a
      measure of language proficiency. In Experiment 2 we also compared students in
      their first/initial (Y1) and fourth/final (Y4) year of either language or
      literature studies. There were no differences between both groups in category
      fluency. In selective attention, bilinguals outperformed monolinguals in Y1 and
      this difference remained significant in Y4 despite overall improvement in both
      groups. Contrasting results were found in attentional switching and letter
      fluency: while no differences were found in Y1 in both tasks, in Y4 there was an
      advantage for bilinguals in attentional switching and for monolinguals in letter
      fluency. We conclude that overall late-acquisition non-balanced bilinguals
      experience similar cognitive effects as their early-acquisition balanced
      counterparts. However, different cognitive effects may appear at different stages
      of adult second language acquisition. 

PMID- 25596357
TI  - What regulates neonatal gonocyte migration?

PMID- 25596359
TI  - Detection of prostate cancer in urine by dogs.

PMID- 25596358
TI  - Search for Microorganisms in Men with Urologic Chronic Pelvic Pain Syndrome: A
      Culture-Independent Analysis in the MAPP Research Network.
AB  - PURPOSE: We used next-generation, state-of-the-art, culture independent
      methodology to survey urine microbiota of males with urologic chronic pelvic pain
      syndrome and control participants enrolled in the MAPP Network to investigate a
      possible microbial etiology. MATERIALS AND METHODS: Male patients with urologic
      chronic pelvic pain syndrome and matched controls were asked to provide initial,
      midstream and post-prostatic massage urine specimens. Specimens were analyzed
      with Ibis T-5000 Universal Biosensor technology to provide comprehensive
      identification of bacterial and select fungal species. Differences between
      urologic chronic pelvic pain syndrome and control study participants for the
      presence of species or species variation in a higher taxonomic grouping (genus)
      were evaluated using permutational multivariate analysis of variance and logistic
      regression. RESULTS: Initial and midstream urine specimens were obtained from 110
      (post-prostatic massage urine in 67) participants with urologic chronic pelvic
      pain syndrome and 115 (post-prostatic massage urine in 62) controls. Overall 78,
      73 and 54 species (42, 39 and 27 genera) were detected in initial, midstream and
      post-prostatic massage urine specimens, respectively. Mean (SD) initial,
      midstream and post-prostatic massage urine species count per person was 1.62
      (1.28), 1.38 (1.36) and 1.33 (1.24) for cases, and 1.75 (1.32), 1.23 (1.15) and
      1.56 (0.97) for controls, respectively. Overall species and genus composition
      differed significantly between participants with urologic chronic pelvic pain
      syndrome and controls in initial stream urine (p=0.002 species level, p=0.004
      genus level), with Burkholderia cenocepacia overrepresented in urologic chronic
      pelvic pain syndrome. No significant differences were observed at any level in
      midstream or post-prostatic massage urine samples. CONCLUSIONS: Assessment of
      baseline culture-independent microbiological data from male subjects enrolled in
      the MAPP Network has identified overrepresentation of B. cenocepacia in urologic
      chronic pelvic pain syndrome. Future studies are planned to further evaluate
      microbiota associations with variable and changing urologic chronic pelvic pain
      syndrome symptom patterns.

PMID- 25596360
TI  - Elevated Dihydrotestosterone is Associated with Testosterone Induced
      Erythrocytosis.
AB  - PURPOSE: Erythrocytosis is the most common dose limiting adverse effect of
      testosterone therapy but the mechanisms of testosterone mediated erythropoiesis
      remain unclear. In this study we examine risk factors for erythrocytosis
      associated with testosterone therapy. MATERIALS AND METHODS: A retrospective
      review was performed of 179 hypogonadal men on testosterone therapy at a single
      andrology clinic. Demographic data, testosterone therapy formulation and duration
      of treatment, and 5alpha-reductase inhibitor use were assessed. Serum
      dihydrotestosterone, total testosterone, free testosterone, follicle-stimulating
      hormone, luteinizing hormone, hematocrit and lipid levels were extracted, and
      changes during treatment were determined. Spearman's rank correlation was used to
      identify relationships between change in hematocrit and study variables. RESULTS:
      Of 179 patients 49 (27%) experienced a 10% or greater change in hematocrit and
      erythrocytosis (hematocrit 50% or greater) developed in 36 (20.1%) at a median
      followup of 7 months. Topical gels were used by 41.3% of patients, injectable
      testosterone by 52.5% and subcutaneous pellets by 6.1%. More men who experienced
      a change in hematocrit of 10% or greater used injectable testosterone than men
      with a change in hematocrit of less than 10% (65% vs 48%, p=0.035), and were less
      likely to be on a 5alpha-reductase inhibitor (2% vs 15%, p=0.017). Men with a
      change in hematocrit of 10% or greater had higher posttreatment
      dihydrotestosterone levels (605.0 vs 436.0 ng/dl, p=0.017) and lower luteinizing
      hormone and follicle-stimulating hormone levels than men with a change in
      hematocrit of less than 10%. Spearman's rank correlations yielded relationships
      between change in hematocrit and posttreatment dihydrotestosterone rho=0.258,
      p=0.001) and total testosterone (rho=0.171, p=0.023). CONCLUSIONS:
      Dihydrotestosterone may have a role in testosterone therapy related
      erythrocytosis and monitoring dihydrotestosterone levels during testosterone
      therapy should be considered. In men in whom erythrocytosis develops, 5alpha
      reductase inhibitors may be therapeutic.

PMID- 25596361
TI  - Are mast cells still good biomarkers for bladder pain syndrome/interstitial
      cystitis?
AB  - PURPOSE: ESSIC identifies mast cell infiltrates of detrusor muscle as a
      diagnostic criterion for bladder pain syndrome/interstitial cystitis. However, an
      increased mast cell count is also characteristic of overactive bladder syndrome.
      The lack of uniformity in mast cell detection methods hampers data comparison.
      Using state-of-the-art techniques we investigated whether mast cells differ among
      bladder conditions. MATERIALS AND METHODS: We analyzed bladder biopsies from 56
      patients, including 31 with bladder pain syndrome/interstitial cystitis with (12)
      or without (19) Hunner lesions, 13 with overactive bladder syndrome and 12
      without bladder symptoms to determine the quantity, location, distribution and
      activation of mast cells using immunohistochemistry with anti-mast cell tryptase.
      Patients were allocated to study groups by key bladder symptoms commonly used to
      define conditions (pain and major urgency). RESULTS: Subepithelial mast cell
      localization (p <0.001) and an increased detrusor mast cell count (p = 0.029)
      were characteristic of bladder pain syndrome/interstitial cystitis with Hunner
      lesions. The optimal cutoff of 32 detrusor mast cells per mm(2) achieved only 68%
      accuracy with 38% positive predictive value. No difference was observed between
      bladder pain syndrome/interstitial cystitis without Hunner lesions and overactive
      bladder syndrome. Patient groups differed in lymphocyte infiltration (p = 0.001),
      nodular lymphocyte aggregates (p <0.001) and urothelium integrity (p <0.001).
      CONCLUSIONS: Subepithelial mast cell distribution was characteristic of bladder
      pain syndrome/interstitial cystitis with Hunner lesions. Detrusor mastocytosis
      had poor predictive value for bladder pain syndrome/interstitial cystitis. Mast
      cell assessment did not distinguish bladder pain syndrome/interstitial cystitis
      without Hunner lesions from overactive bladder syndrome.

PMID- 25596362
TI  - Novel biomarkers and advanced imaging modalities in the early detection of
      prostate cancer.

PMID- 25596365
TI  - In situ quartz crystal microbalance monitoring of the adsorption of
      polyoxometalate on a polyampholyte polymer matrix.
AB  - Hybridization of polyoxometalates (POMs) via an organic-inorganic association
      constitutes a new route to develop heterogeneous POM catalysts with tunable
      supramolecular architecture. As the structural stability of POMs is strongly
      influenced by the pH conditions, a quantitative understanding of the POMs-polymer
      association is important in practical applications. Herein, we use Quartz Crystal
      Microbalance (QCM) to systematically investigate the interactions of Keggin
      phosphotungstic acid POM with a polyampholyte polymer-coated QCM sensor as a
      function of pH. The mass of adsorbed POMs increases when pH decreases from 5.6 to
      2, indicating that electrostatic forces play a major role in the formation of POM
      polymer hybrids. This finding is complemented by AFM images that show an increase
      in the size of the hybrid entities from 5 to 12 nm as the pH decreases from 5.6
      to 2. The POM adsorbed amount at a particular pH value reaches an equilibrium
      level with time. The hybrids further gain in adsorbed mass only when lowering the
      pH value of the POM solution. The hybrid structure formed above pH 2 shows
      resistance to leaching as indicated by the steady level of the adsorbed mass
      during a rinsing step with water. However, at pH 2, the rinsing step causes
      desorption of some weakly adsorbed POMs. It is shown that leached POMs can be re
      adsorbed back into the polymer matrix during a second contact with a POM solution
      at pH 2. This adsorption-desorption cycles of POMs were successfully repeated.
      Our experiments shed light into the coexistence of tightly as well as loosely
      bound POMs in hybrid catalyst formed at pH 2. The loosely bound POMs can
      potentially act as homogeneous catalysts when desorbed. However, these leached
      POMs can be re-adsorbed back into the matrix, preserving the heterogeneous state
      of the catalyst. Our results show that QCM is a powerful technique to study in
      situ the dynamics of the adsorption of POMs on a polymer matrix under different
      pH conditions.

PMID- 25596364
TI  - Resolution revolution: epilepsy dynamics at the microscale.
AB  - Our understanding of the neuronal mechanisms behind epilepsy dynamics has
      recently advanced due to the application of novel technologies, monitoring
      hundreds of neurons with single cell resolution. These developments have provided
      new theories on the relationship between physiological and pathological states,
      as well as common motifs for the propagation of paroxysmal activity. Although
      traditional electroencephalogram (EEG) recordings continue to describe normal
      network oscillations and abnormal epileptic events within and outside of the
      seizure focus, analysis of epilepsy dynamics at the microscale has found
      variability in the composition of macroscopically repetitive epileptiform events.
      These novel results point to heterogeneity in the underlying dynamics of the
      disorder, highlighting both the need and potential for more specific and targeted
      therapies. 

PMID- 25596366
TI  - Use of alginate, chitosan and cellulose nanocrystals as emulsion stabilizers in
      the synthesis of biodegradable polymeric nanoparticles.
AB  - Biopolymeric nanoparticles (NPs) based on a biodegradable poly(DL-Lactide-co
      Glycolide) PLGA copolymer matrix combined with alginate, chitosan and
      nanostructured cellulose crystals as three different natural emulsion
      stabilizers, were synthesized by a double emulsion (water/oil/water) method with
      subsequent solvent evaporation. The morphological, thermal, chemical and
      rheological properties of the novel designed NPs and the effect of the different
      emulsion stabilizers used during the synthesis were deeply investigated in order
      to optimize the synthesis procedure and the development of biodegradable
      nanoparticles coated with natural polymers. The morphological analysis of the
      produced nanoparticles showed that all the different formulations presented a
      spherical shape with smooth surface. Infrared spectroscopy investigations showed
      that the PLGA copolymer maintained its backbone structure and confirmed the
      presence of chitosan, alginate and cellulose nanocrystals (CNC) on the
      nanoparticle surface. The obtained results suggest that PLGA nanoparticles with
      CNC as emulsion stabilizer might represent promising formulations opening new
      perspective in the field of self-assembly of biodegradable nanomaterials for
      medical and pharmaceutical applications.

PMID- 25596367
TI  - Flotation selectivity of novel alkyl dicarboxylate reagents for apatite-calcite
      separation.
AB  - The investigation aims to demonstrate the conceptual thoughts behind developing
      mineral specific reagents for use in flotation of calcium containing ores. For
      this purpose, a series of dicarboxylate-based surfactants with varying distance
      between the carboxylate groups (one, two or three methylene groups) was
      synthesized. A surfactant with the same alkyl chain length but with only one
      carboxylate group was also synthesized and evaluated. The adsorption behavior of
      these new reagents on pure apatite and pure calcite surfaces was studied using
      Hallimond tube flotation, FTIR and zeta potential measurements. The relation
      between the adsorption behavior of a given surfactant at a specific mineral
      surface and its molecular structure over a range of concentrations and pH values,
      as well as the region of maximum recovery, was established. It was found that one
      of the reagents, with a specific distance between the carboxylate groups, was
      much more selective for a particular mineral surface than the other homologues.
      For example, out of the four compounds synthesized, only the one where the
      carboxylate groups were separated by a single methylene group floated apatite but
      not calcite, whereas calcite was efficiently floated with the monocarboxylic
      reagent, but not with the other reagents synthesized. This selective adsorption
      of a given surfactant to a particular mineral surface relative to other mineral
      surfaces as evidenced in the flotation studies was substantiated by zeta
      potential and infra-red spectroscopy data. 

PMID- 25596368
TI  - Gradient Theory simulations of pure fluid interfaces using a generalized
      expression for influence parameters and a Helmholtz energy equation of state for
      fundamentally consistent two-phase calculations.
AB  - The fidelity of Gradient Theory simulations depends on the accuracy of saturation
      properties and influence parameters, and require equations of state (EoS) which
      exhibit a fundamentally consistent behavior in the two-phase regime. Widely
      applied multi-parameter EoS, however, are generally invalid inside this region.
      Hence, they may not be fully suitable for application in concert with Gradient
      Theory despite their ability to accurately predict saturation properties. The
      commonly assumed temperature-dependence of pure component influence parameters
      usually restricts their validity to subcritical temperature regimes. This may
      distort predictions for general multi-component interfaces where temperatures
      often exceed the critical temperature of vapor phase components. Then, the
      calculation of influence parameters is not well defined. In this paper, one of
      the first studies is presented in which Gradient Theory is combined with a next
      generation Helmholtz energy EoS which facilitates fundamentally consistent
      calculations over the entire two-phase regime. Illustrated on pentafluoroethane
      as an example, reference simulations using this method are performed. They
      demonstrate the significance of such high-accuracy and fundamentally consistent
      calculations for the computation of interfacial properties. These reference
      simulations are compared to corresponding results from cubic PR EoS, widely
      applied in combination with Gradient Theory, and mBWR EoS. The analysis reveals
      that neither of those two methods succeeds to consistently capture the
      qualitative distribution of obtained key thermodynamic properties in Gradient
      Theory. Furthermore, a generalized expression of the pure component influence
      parameter is presented. This development is informed by its fundamental
      definition based on the direct correlation function of the homogeneous fluid and
      by presented high-fidelity simulations of interfacial density profiles. The new
      model preserves the accuracy of previous temperature-dependent expressions,
      remains well-defined at supercritical temperatures, and is fully suitable for
      calculations of general multi-component two-phase interfaces. 

PMID- 25596369
TI  - Incorporation of polymerizable surfactants in hydroxyethyl methacrylate lenses
      for improving wettability and lubricity.
AB  - Dryness and discomfort are the main reasons for dropouts in contact lens wearers.
      Incorporating surfactants in lens formulations could improve wettability and
      lubricity, which can improve comfort. We have focused on incorporating
      polymerizable surfactants in hydroxyethyl methacrylate lenses to improve comfort,
      while minimizing the potential for surfactant release into the tears. The
      surfactants were added to the polymerization mixture, followed by UV curing and
      extraction of leachables in hot water. Wettability and lubricity were
      characterized by measuring the contact angle and coefficient of friction. Lenses
      were also characterized by measuring transmittance, loss and storage moduli and
      ion permeability. Incorporation of surfactants significantly reduced contact
      angle from 90 degrees  for p-HEMA gels to about 10 degrees  for 2.43% (w/w)
      surfactant loading in hydrated gel. The coefficient of friction also decreased
      from about 0.16 for HEMA gels to 0.05 for the gels with 2.43% surfactant loading.
      There was a good correlation between the contact angle and coefficient of
      friction suggesting that both effects can be related to the stretching of the
      surfactant tails near the surface into the aqueous phase. The water content was
      also correlated with the surfactant loading but the contact angle was more
      sensitive suggesting that the observed improvements in wettability and lubricity
      arise from the protrusion of the surfactant tails in into the liquid, and not
      purely from the increase in the water content. The gels were clear and certain
      compositions also have the capability to block UVC and UVB radiation. The results
      suggest that incorporation of polymerizable surfactants could be useful in
      improving surface properties without significantly impacting any bulk property. 

PMID- 25596370
TI  - Linear and nonlinear optical properties of functionalized CdSe quantum dots
      prepared by plasma sputtering and wet chemistry.
AB  - We develop an innovative manufacturing process, based on radio-frequency
      magnetron sputtering (RFMS), to prepare neat CdSe quantum dots (QDs) on glass and
      silicon substrates and further chemically functionalize them. In order to
      validate the fabrication protocol, their optical properties are compared with
      those of QDs obtained from commercial solutions and deposited by wet chemistry on
      the substrates. Firstly, AFM measurements attest that nano-objects with a mean
      diameter around 13 nm are located on the substrate after RFMS treatment.
      Secondly, the UV-Vis absorption study of this deposited layer shows a specific
      optical absorption band, located at 550 nm, which is related to a discrete energy
      level of QDs. Thirdly, by using two-color sum-frequency generation (2C-SFG)
      nonlinear optical spectroscopy, we show experimentally the functionalization
      efficiency of the RFMS CdSe QDs layer with thiol derived molecules, which is not
      possible on the QDs layer prepared by wet chemistry due to the surfactant
      molecules from the native solution. Finally, 2C-SFG spectroscopy, performed at
      different visible wavelengths, highlights modifications of the vibration mode
      shape whatever the QDs deposition method, which is correlated to the discrete
      energy level of the QDs.

PMID- 25596371
TI  - Study on metal nanoparticles synthesis and orientation of gemini surfactant
      molecules used as stabilizer.
AB  - In the present study, we report the synthesis of gold (Au), silver (Ag), and gold
      silver alloy (Au-Ag) nanoparticles (NPs) by seed-mediated method using gemini
      surfactant, containing diethyl ether spacer group as a stabilizer. As-synthesized
      NPs are found very much stable and have been characterized using UV-vis
      spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron
      microscopy (TEM), energy dispersive spectroscopy (EDS), and zeta potential
      techniques. The orientation of gemini surfactant molecules surrounding the metal
      NPs has been investigated exploiting twisted intramolecular charge transfer
      (TICT) fluorescence properties of a probe 4-(N,N-dimethylamino) cinnamaldehyde
      (DMACA). The quenching efficiencies of different NPs have been performed in the
      fluorescence of DMACA and are found to be different. This effect can be related
      to the location of DMACA as well as the electro-negativity of the metals as the
      extent of orientation of the surfactant molecules around NPs controls the
      location of DMACA in a bilayer. To support the location of DMACA, fluorescence
      quenching studies with cetylpyridinium chloride (CPC) as an external quencher
      have also been carried out. 

PMID- 25596372
TI  - The effect of temperature on supported dipalmitoylphosphatidylcholine (DPPC)
      bilayers: structure and lubrication performance.
AB  - Phospholipids fulfill an important role in joint lubrication. They, together with
      hyaluronan and glycoproteins, are the biolubricants that sustain low friction
      between cartilage surfaces bathed in synovial fluid. In this work we have
      investigated how the friction force and load bearing capacity of 1,2-dipalmitoyl
      sn-glycero-3-phosphocholine (DPPC) bilayers on silica surfaces are affected by
      temperature, covering the temperature range 25-52 degrees C. Friction forces have
      been determined utilizing the AFM colloidal probe technique, which showed that
      DPPC bilayers are able to provide low friction forces over the whole temperature
      interval. However, the load bearing capacity is improved at higher temperatures.
      We interpret this finding as being a consequence of lower rigidity and higher
      self-healing capacity of the DPPC bilayer in the liquid disordered state compared
      to the gel state. The corresponding structure of solid supported DPPC bilayers at
      the silica-liquid interface has been followed using X-ray reflectivity
      measurements, which suggests that the DPPC bilayer is in the gel phase at 25
      degrees C and 39 degrees C and in the liquid disordered state at 55 degrees C.
      Well-defined bilayer structures were observed for both phases. The deposited DPPC
      bilayers were also imaged using AFM PeakForce Tapping mode, and these
      measurements indicated a less homogeneous layer at temperatures below 37 degrees
      C. 

PMID- 25596373
TI  - Measurement of social capital in relation to health in low and middle income
      countries (LMIC): a systematic review.
AB  - Social capital is a neglected determinant of health in low and middle income
      countries. To date, majority of evidence syntheses on social capital and health
      are based upon high income countries. We conducted this systematic review to
      identify the methods used to measure social capital in low and middle-income
      countries and to evaluate their relative strengths and weaknesses. An electronic
      search was conducted using Pubmed, Science citation index expanded, Social
      science citation index expanded, Web of knowledge, Cochrane, Trip, Google scholar
      and selected grey literature sources. We aimed to include all studies conducted
      in low and middle-income countries, published in English that have measured any
      aspect of social capital in relation to health in the study, from 1980 to January
      2013. We extracted data using a data extraction form and performed narrative
      synthesis as the measures were heterogeneous. Of the 472 articles retrieved, 46
      articles were selected for the review. The review included 32 studies from middle
      income countries and seven studies from low income countries. Seven were cross
      national studies. Most studies were descriptive cross sectional in design (n =
      39). Only two randomized controlled trials were included. Among the studies
      conducted using primary data (n = 32), we identified18 purposely built tools that
      measured various dimensions of social capital. Validity (n = 11) and reliability
      (n = 8) of the tools were assessed only in very few studies. Cognitive constructs
      of social capital, namely trust, social cohesion and sense of belonging had a
      positive association towards measured health outcome in majority of the studies.
      While most studies measured social capital at individual/micro level (n = 32),
      group level measurements were obtained by aggregation of individual measures. As
      many tools originate in high income contexts, cultural adaptation, validation and
      reliability assessment is mandatory in adapting the tool to the study setting.
      Evidence on causality and assessing predictive validity is a problem due to the
      scarcity of prospective study designs. We recommend Harpham et al. s' Adapted
      Social Capital Assessment Tool (A-SCAT), Hurtado et al. s' six item tool and
      Elgar et al. s' World Value Survey Social Capital Scale for assessment of social
      capital in low and middle income countries.

PMID- 25596374
TI  - Cognitive function and health-related quality of life four years after cardiac
      arrest.
AB  - AIM: Neuropsychological testing has uncovered cognitive impairment in cardiac
      arrest survivors with good neurologic outcome according to the cerebral
      performance categories. We investigated cognitive function and health-related
      quality of life four years after cardiac arrest. METHODS: Thirty cardiac arrest
      survivors over the age of 18 in cerebral performance category 1 or 2 on hospital
      discharge completed the EQ-5D-5L and HADS questionnaires prior to cognitive
      testing using the Cambridge Neuropsychological Test Automated Battery. The
      results were compared with population norms. RESULTS: Twenty-nine per cent of
      patients were cognitively impaired. The pattern of cognitive impairment reflects
      dysfunction in the medial temporal lobe, with impaired short-time memory and
      executive function slightly but distinctly affected. There was a significant
      reduction in quality of life on the EQ-VAS, but not on the EQ index. CONCLUSION:
      Cognitive impairment four years after cardiac arrest affected more than one
      quarter of the patients. Short-term memory was predominantly affected.

PMID- 25596375
TI  - Liposomal insulin promoter-thymidine kinase gene therapy followed by ganciclovir
      effectively ablates human pancreatic cancer in mice.
AB  - PDX1 is overexpressed in pancreatic cancer, and activates the insulin promoter
      (IP). Adenoviral IP-thymidine kinase and ganciclovir (TK/GCV) suppresses human
      pancreatic ductal carcinoma (PDAC) in mice, but repeated doses carry significant
      toxicity. We hypothesized that multiple cycles of liposomal IP-TK/GCV ablate
      human PDAC in SCID mice with minimal toxicity compared to adenoviral IP-TK/GCV.
      SCID mice with intraperitoneal human pancreatic cancer PANC-1 tumor implants were
      given a single cycle of 35 ug iv L-IP-TK, or four cycles of 1, 10, 20, 30, or 35
      ug iv L-IP-TK (n = 20 per group), followed by intraperitoneal GCV. Insulin and
      glucose levels were monitored in mice treated with four cycles of 35 ug iv L-IP
      TK. We found that four cycles of 10-35 ug L-IP-TK/GCV ablated more PANC-1 tumor
      volume compared to a single cycle with 35 ug. Mice that received four cycles of
      10 ug L-IP-TK demonstrated the longest survival (P < 0.05), with a median
      survival of 126 days. In comparison, mice that received a single cycle of 35 ug L
      IP-TK/GCV or GCV alone survived a median of 92 days and 68.7 days, respectively.
      There were no significant changes in glucose or insulin levels following
      treatment. In conclusion, multiple cycles of liposomal IP-TK/GCV ablate human
      PDAC in SCID mice with minimal toxicity, suggesting non-viral vectors are
      superior to adenoviral vectors for IP-gene therapy. 

PMID- 25596376
TI  - Nanoparticle delivery of HIF1alpha siRNA combined with photodynamic therapy as a
      potential treatment strategy for head-and-neck cancer.
AB  - Combination therapy has become a major strategy in cancer treatment. We used
      anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently
      deliver HIF1alpha siRNA to the cytoplasm of sigma receptor-expressing SCC4 and
      SAS cells that were also subjected to photodynamic therapy (PDT). HIF1alpha siRNA
      nanoparticles effectively reduced HIF1alpha expression, increased cell death, and
      significantly inhibited cell growth following photosan-mediated photodynamic
      therapy in cultured cells. Intravenous injection of the same nanoparticles into
      human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA
      accumulation and reduced HIF1alpha expression in tumor tissues. When combined
      with photodynamic therapy, HIF1alpha siRNA nanoparticles enhanced the regression
      in tumor size resulting in a ~40% decrease in volume after 10 days. Combination
      therapy was found to be substantially more effective than either HIF1alpha siRNA
      or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker
      studies support this conclusion. Our results show the potential use of LCP
      nanoparticles for efficient delivery of HIF1alpha siRNA into tumors as part of
      combination therapy along with PDT in the treatment of oral squamous cell
      carcinoma. 

PMID- 25596378
TI  - Characterization of antibody drug conjugate positional isomers at cysteine
      residues by peptide mapping LC-MS analysis.
AB  - Antibody-drug conjugates (ADCs) are becoming a major class of oncology
      therapeutics. Because ADCs combine the monoclonal antibody specificity with the
      high toxicity of a drug, they can selectively kill tumor cells while minimizing
      toxicity to normal cells. Most of the current ADCs in clinical trials are
      controlled, but heterogeneous mixtures of isomers and isoforms. Very few
      protocols on ADC characterization at the peptide level have been published to
      date. Here, we report on the improvement of an ADC peptide mapping protocol to
      characterize the drug-loaded peptides by LC-MS analysis. These methods were
      developed on brentuximab vedotin (Adcetris), a commercial ADC with an average of
      four drugs linked to interchain cysteine residues of its antibody component.
      Because of the drug hydrophobicity, all the steps of this protocol including
      enzymatic digestion were improved to maintain the hydrophobic drug-loaded
      peptides in solution, allowing their unambiguous identification by LC-MS. For the
      first time, the payloads positional isomers observed by RP-HPLC after IdeS
      digestion and reduction of the ADC were also characterized.

PMID- 25596379
TI  - Proteomic analysis of individual fruit fly hemolymph.
AB  - Analysis of blood proteins holds critical promise for in depth understanding of
      physiological states. Protein content of hemolymph from Drosophila melanogaster
      is of particular analytical interest because the insect open circulatory system
      involves chemical signaling through the hemolymph. The challenge of working with
      this sample, however, is the nanoliter volumes of solution available for
      analysis. In this study, we developed a novel hyphenated Agilent nano-HPLC chip
      column-MS method to obtain proteomic information from individual fruit fly
      hemolymph, using a low-volume sample collection technique established previously.
      The total amount of individual Drosophila hemolymph protein is determined around
      0.798 +/- 0.251 MUg/100 nL based upon a Bradford assay with BSA. Hemolymph
      samples around 50 nL were collected from single flies and digested using a
      customized micro-scale digestion protocol. Mass spectral analysis shows a total
      of 19 proteins were identified from the hemolymph of individual flies. Of these
      findings, 6 novel proteins have been identified for the first time with evidence
      at the translation level. Detection of 13 proteins well-known in the literature
      speaks to the method's validity and demonstrates the ability to reproducibly
      analyze volume-limited samples from individual fruit flies for protein content.
      This nano-scale analysis method will facilitate future study of Drosophila and
      lead to a more complete understanding of the physiology of the fly model system.

PMID- 25596377
TI  - Is vaccine type seropositivity a marker for human papillomavirus vaccination?
      National Health and Nutrition Examination Survey, 2003-2010.
AB  - OBJECTIVE: Since 2006, human papillomavirus (HPV) vaccination has been routinely
      recommended for adolescent females in the USA. The quadrivalent vaccine induces
      long-term seropositivity to HPV 6/11/16, which may be useful as a marker for HPV
      vaccine coverage. METHODS: We evaluated vaccine type seropositivity (i.e.,
      seropositivity to HPV 6/11/16 with or without HPV18) among females aged 14-59
      years participating in the 2003-2010 National Health and Nutrition Examination
      Survey (cross-sectional, nationally representative surveys). We compared pre
      vaccine era (2003-2006) to vaccine era (2007-2010) seropositivity and assessed
      agreement between vaccine era seropositivity and reported vaccination by kappa
      statistic. RESULTS: Seropositivity was 1.0% among 2151 females in the pre-vaccine
      era and 22.1% among 1420 females in the vaccine era (p < 0.001); 23.1% of vaccine
      era females reported receipt of one or more HPV vaccine dose. Seropositivity and
      reported vaccination had high agreement (kappa = 0.79; 95% confidence interval
      0.74-0.84). Among seropositive females, 14.5% reported no vaccination.
      CONCLUSION: The increase in vaccine era seropositivity likely reflects
      vaccination uptake. Our study suggests seropositivity to HPV 6/11/16 may be a
      useful marker for vaccination coverage in adolescent and young adult females.
      Discordance between seropositivity and reported vaccination may be explained by
      inaccurate reporting and/or natural exposure to HPV.

PMID- 25596380
TI  - Determination and pharmacokinetic study of pirfenidone in rat plasma by UPLC
      MS/MS.
AB  - A rapid, sensitive and selective ultra-performance liquid chromatography tandem
      mass spectrometry (UPLC-MS/MS) was developed and validated for the determination
      and pharmacokinetic investigation of pirfenidone in rat plasma. Sample
      preparation was accomplished through a simple one-step deproteinization procedure
      with 0.2 mL of acetonitrile to a 0.1 mL plasma sample. Plasma samples were
      separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase
      consisting of acetonitrile-0.1% formic acid in water with gradient elution. The
      total run time was 3.0 min and the elution of pirfenidone was at 1.39 min. The
      detection was performed on a triple quadrupole tandem mass spectrometer in the
      multiple reaction-monitoring (MRM) mode using the respective transitions m/z
      186.2->92.1 for pirfenidone and m/z 237.1->194.2 for carbamazepine (IS),
      respectively. The calibration curve was linear over the range of 5-2000 ng/mL
      with a lower limit of quantitation (LLOQ) of 5 ng/mL. Mean recovery of
      pirfenidone in plasma was in the range of 80.4-84.3%. Intra-day and inter-day
      precision were both <12.1%. This method was successfully applied in
      pharmacokinetic study after oral administration of 10.0mg/kg pirfenidone in rats.

PMID- 25596381
TI  - Isolation of isochlorogenic acid isomers in flower buds of Lonicera japonica by
      high-speed counter-current chromatography and preparative high performance liquid
      chromatography.
AB  - An efficient method was established by HSCCC combined with prep-HPLC for
      separating isochlorogenic acid isomers from flower buds of Lonicera japonica. The
      partially purified sample from the methanol extract of flower buds of L. japonica
      by silica gel column was separated by HSCCC to result in a fraction containing
      two isochlorogenic acid isomers. The fraction was further isolated by prep-HPLC
      to yield isochlorogenic acid A and isochlorogenic acid C with purities of 98% and
      96%, and the total recoveries at 80.1% and 79.8%, respectively. The chemical
      structures of isochlorogenic acid isomers were confirmed by electrospray
      ionization mass spectrometry (ESI-MS) and (1)H nuclear magnetic resonance (NMR). 

PMID- 25596382
TI  - Recurrent iliac hydatidosis: A case report.
AB  - INTRODUCTION: Hydatid cysts may occur in any area of the body, but they usually
      localize to the liver and the lungs. Primary localization in bone is not common.
      PRESENTATION OF CASE: The authors report the case of multifocal hydatid disease
      appeared 3 years after the surgical treatment of a cyst of the hip. The patient
      presented with cough and chest pain of 2 months duration. Only the lung
      localization was symptomatic. The thoracic echography, the abdominal and chest
      scan allowed the diagnosis. DISCUSSION: Hydatid recurrence remain frequent,
      whatever is the nature of the treatment, surgical or chemical. CONCLUSION: The
      premature detection of recurrence is of great importance.

PMID- 25596383
TI  - REM sleep as a potential indicator of hyperarousal in psychophysiological and
      paradoxical insomnia sufferers.
AB  - STUDY OBJECTIVES: The objective was to study REM sleep macrostructure and
      microstructure as potential indicators of hyperarousal in insomnia by comparing
      good sleepers (GS) and insomnia sufferers (INS) (subdivided into
      psychophysiological "PSY-I" and paradoxical "PARA-I"). DESIGN: Cross-sectional
      comparisons of GS, PSY-I and PARA-I. SETTING: Participants slept for 4
      consecutive nights in the laboratory where PSG was recorded. Nights 2 and 3 were
      combined to compare REM sleep between groups. PARTICIPANTS: Thirty-nine PSY-I, 27
      PARA-I and 47 GS completed the study, comprising home questionnaires, clinical
      interviews and night PSG recordings. All participants were aged between 25 and 55
      and met inclusion criteria for either PSY-I, PARA-I or GS. INTERVENTIONS N/A
      MEASUREMENTS AND RESULTS: Results showed no between group differences on REM
      sleep macrostructure. As for REM sleep microstructure, PSY-I had an increased
      number of wake intrusions compared to PARA-I (p=.03). Subjective SE, TST and TWT
      were significantly correlated with the duration of REM sleep (REMD; p<=.002) and
      with the proportion of REM sleep for PARA-I (p<=.06). CONCLUSIONS: REM sleep
      macrostructure does not seem to be an adequate indicator of hyperarousal in
      insomnia. However, the number of wake intrusions in REM could be used to
      differentiate PSY-I from PARA-I and could reflect the heightened arousal of the
      former group. Relationships between REM sleep duration and proportion could be
      linked to dream imagery activity, especially in PARA-I. Further investigations
      are needed to identify variables that could reflect hyperarousal and
      differentiate insomnia types.

PMID- 25596384
TI  - Head of Cancer Drugs Fund regrets its establishment, conference hears.

PMID- 25596385
TI  - Doctors facing complaints have severe depression and suicidal thoughts, study
      finds.

PMID- 25596388
TI  - [The Living Will does not surrogate a good clinical practice].

PMID- 25596387
TI  - Firm action needed on predatory journals.

PMID- 25596389
TI  - [Finances and health].

PMID- 25596386
TI  - Family Density and SES Related to Diabetes Management and Glycemic Control in
      Adolescents With Type 1 Diabetes.
AB  - OBJECTIVE: Youth with Type 1 diabetes (T1D) from single-parent families have
      poorer glycemic control; a finding confounded with socioeconomic status (SES).
      Family density (FD), or youth:adult ratio, may better characterize family risk
      status. METHODS: Structural equation modeling assessed the relation of single
      parent status, SES, and FD to parenting stress, diabetes-related conflict,
      parental monitoring, adherence, and glycemic control using cross-sectional parent
      and youth data (n = 257). RESULTS: Single-parent status exhibited similar
      relations as SES and was removed. Lower FD was associated with better glycemic
      control (beta = -.29, p = .014) via less conflict (beta = .17, p = .038) and
      greater adherence (beta = -.54, p < .001). CONCLUSIONS: Beyond SES, FD plays a
      significant role in adherence and glycemic control via diabetes-related conflict.
      In contrast, the effects of single-parent status were indistinguishable from
      those of SES. FD provides distinct information related to adolescent glycemic
      control.

PMID- 25596390
TI  - Radiofrequency ablation of atrial fibrillation during concomitant cardiac
      surgery.
AB  - OBJECTIVES: We present the experience of our centre with radiofrequency ablation
      of atrial fibrillation concomitantly with cardiac surgery Methods: 170 patients
      underwent atrial fibrillation ablation with uni/bipolar-radiofrequency. They were
      followed for 3-months and then as appropriate for the cardiac disease. In 2013,
      patients still alive underwent rhythm monitoring with ECG and 24-hour tape if in
      sinus rhythm RESULTS: Mean age was 65 years old and 42% of the patients were
      male. Paroxysmal AF was rare (7%). Most patients had preserved ejection fraction
      and dilated left atria (diameter 53.2+/-7.5 mm). The most common indication for
      cardiac surgery was valve disease. More than 75% of the patients underwent
      prophylactic closure of the left atrial appendage. Pulmonary vein isolation was
      performed in all patients, followed by other left atrial ablation lines. Overall,
      surgical complications were rare, being the most frequent pacemaker implantation
      (15%). Median length of stay was 9 days (p25-p75:7-14). At discharge, 69% of the
      patients were in sinus rhythm, being 90% on anticoagulation and 69% on
      amiodarone. In-hospital mortality was less than 3% (5 patients), none of them
      related to the ablation procedure. At 3 months, 50% of the patients were in sinus
      rhythm, being 92% on anticoagulation and 75% on antiarrhythmic drugs. Direct
      current cardioversion was successful in 8 of 12 patients. In the multivariate
      analysis, being in sinus rhythm at discharge was the single independent predictor
      of maintaining sinus rhythm at 3 months. In 2013 (469 patients-year), 40% of the
      patients were in sinus rhythm, being 80% on anticoagulation and 45% on
      antiarrhythmic drugs. CONCLUSIONS: Concurrent atrial fibrillation ablation with
      radiofrequency achieves satisfactory and stable recovery of sinu rhythm without
      adding significant operative risk and post-operative complications.

PMID- 25596392
TI  - [Analysis of mortality of patients undergoing veno-venous hemofiltration after
      cardiac surgery].
AB  - OBJECTIVE: In this study we aim to assess the mortality of patients undergoing
      cardiac surgery and that in the post operative period required veno-venous
      hemofiltration. METHODS: The population studied includes 77 patients (44 men and
      33 women, with mean age 67,04+/-12.99 years), that underwent cardiac surgery
      between January 2008 and March 2013, requiring veno-venous hemofiltration after
      surgery. 3 surgeries were urgent, 3 emergent and the other elective, 18 of which
      were re operations. 31 patients underwent valvular surgery, 14 myocardial
      revascularization surgery, 8 patients combined valvular and myocardial
      revascularization surgery and 22 patients other surgery. The mean EuroScore I of
      the study group was 15,8% (maximum of 57 and minimum of 2.2%). The mean length of
      stay in the intensive care unit was 18 days (maximum of 185 days and minimum of 1
      day). The mean length of hospital stay was 26 days (maximum of 190 days and
      minimum of 1 day). RESULTS: The overall mortality of the study group was 40,3%
      (31 patients), the hospital mortality was 31,2%(24 patients) and mortality after
      discharge was 9,1% (7 patients). The mean EuroScore of patients undergoing
      cardiac surgery alone was 5,8% and the hospital mortality was 2,8%. Mortality
      after 1 year follow up was 6.1%. CONCLUSIONS: Patients undergoing veno-venous
      hemofiltration have a much higher EuroScore and mortality rate when compared to
      the population undergoing cardiac surgery alone. We conclude that the mortality
      of patients undergoing cardiac surgery and that require hemofiltration after
      surgery is similar to the other published studies regarding this type of patient.

PMID- 25596391
TI  - Mid-term outcomes of mitral valve repair in a low-volume hospital.
AB  - INTRODUCTION: Mitral valve repair is feasible for all patients with mitral
      regurgitation and its advantages are well documented; however, there is general
      agreement that it is technically demanding and that success rates are related to
      volume/ experience centers. The aim of this study was to evaluate the clinical
      and echocardiographic mid-term outcomes of patients who underwent a mitral repair
      in a low-volume hospital. METHODS AND RESULTS: Between 2009 and 2014, 55 patients
      (23 female) with mitral regurgitation underwent mitral repair. The mean age was
      60.7+/-11.4 years (range, 21-81 yr). The most prevalent cardiovascular risk
      factors were: hypertension 61.8%, dyslipidemia 47.3% and diabetes 21.8%. Nine
      patients (16.4%) were in class III-IV of NYHA and ten (18.2%) had atrial
      fibrillation. Repair procedures included mitral ring annuloplasty (n=55),
      quadrangular resection (n=20), chordal replacement (n=13) and commissuroplasty
      (n=5). Postoperative complications included atrial fibrillation 16.4%, check
      bleeding 3.6%, wound infection 1.8% and renal failure 1.8%. The hospital
      mortality rate was 1.8%. Follow-up echocardiography (median 19+/-5 months)
      revealed trivial or no mitral regurgitation in 38.2%, mild (1+) in 34.5% and
      severe (3+) only in 3 patients. CONCLUSION: In the current era, patients
      undergoing successful mitral valve repair have low mortality and morbidity even
      in low-volume hospitals.

PMID- 25596393
TI  - Prevalence and risk analysis for depression after open-heart valve replacement
      surgery.
AB  - BACKGROUND AND PURPOSE: Cardiac surgery may account for long term complications
      as depression. Geriatric Depression Scale (GDS) is a reliable 30-item
      questionnaire for assessing depressive symptoms in several populations. The aim
      of the present study was to determine the prevalence and predictors of depression
      after open-heart valve replacement surgery in a portuguese population. METHODS:
      Prospective observational study enrolling 52 patients (55.8% men, mean age 67.7
      +/- 11.3 years) with no history of depression, submitted to elective open-heart
      valve replacement surgery. Patients completed the GDS questionnaire at 6-month
      follow-up. Cardiovascular risk factors, medical history, left ventricular
      function, prescription table, analytical and surgical variables and length of
      hospital stay were collected to verify its influence on postoperative depression.
      RESULTS: Twenty-seven patients (41.4% men, mean age 69.3 +/- 10.3 years) had
      scores consistent with symptoms of depression (GDS score >10), representing 51.9%
      of the sample. Twenty-one (77.8%) were mildly depressed, 6 (22.2%) were severely
      depressed and only 4 (19.0%) and 3 (50.0%) were on antidepressants, respectively.
      Postoperative complications (29.6 vs 8.0%, p=0.045), lower postoperative
      hemoglobin concentration (8.9 +/- 0.8 vs 9.8 +/- 1.5 g/dL p=0.015) and longer
      time of hospitalization (12.2 +/- 7.7 vs 8.2 +/- 3.4 days, p=0.020) were found to
      be significant predictors for postoperative depression. No other statistically
      significant differences were found. CONCLUSION: Depression after open-heart valve
      replacement surgery is frequent but appears to be generally overlooked.
      Strategies for systematic screening and early guidance should be implemented to
      ensure better health and quality-of-life of patients undergoing major cardiac
      surgery.

PMID- 25596394
TI  - [Thoracic nocardiosis - a clinical report].
AB  - Nocardia genus microorganisms are ubiquitous, Gram positive aerobic bacterias,
      responsible for disease mainly in immunocompromised hosts, with cellular immune
      response commitment. Inhalation is the main form of transmition and pulmonary
      disease is the most frequent presentation. Dissemination may occur by contiguity
      and also via hematogenous. The clinical and imaging presentation is not specific,
      and diagnosis is obtained after identification of Nocardia bacteria in biological
      samples. Since there are no reliable studies that indicate the best therapeutic
      option, treatment should be individualized and based on antimicrobial
      susceptibility testing. Surgical drainage should also be considered in all
      patients. The authors present a clinical case of a patient with thoracic
      nocardiosis, and make a short literature review on the theme. 

PMID- 25596395
TI  - [TEVAR: a strategy for the diversity of thoracic aorta disease. Series of cases
      and national prospect].
AB  - OBJECTIVE: To assess endovascular treatment of thoracic aorta diseases in a
      national centre of angiology and vascular surgery. To quantify the national
      registry of TEVAR's. MATERIAL AND METHODS: This unicentric and retrospective
      study included patients submitted to TEVAR until the end of 2012. Twenty-seven
      patients were considered high-risk for conventional surgery: 14 degenerative
      thoracic aorta aneurysms or pseudoaneurysms (10 assymptomatic), 1 ruptured
      thoracoabdominal aneurysm, 5 aortabronchial/aortoesophageal fistulas, 3
      complicated dissections, 2 penetrating atherosclerotic ulcer/intramural hematoma,
      1 traumatic laceration and 1 embolization from aortic plaque. Eighteen (67%) were
      emergent/urgent procedures. RESULTS: At the institutional level, immediate
      technical success was achieved in all cases; average follow up was 24 months (0
      97). Thirty days and 24 months global mortality was, respectively, 4% (6% for
      emergent/urgent procedures and 0% for elective procedures) and 13%. Aortic
      related mortality was similar. One case of paraplegia and 2 of case of stoke were
      registered. Endoleak was present in 4 patients. Survival free from aneurysmal sac
      expansion (aneurysm, pseudoaneurysm or dissection, n=16) was 88% at 30 days.
      Survival free from aortic reintervention was 93% at 30 days and 81% at 24 months.
      Nationally, TEVAR registries triplicated from 2007 top 2010. CONCLUSION: These
      results favour the actual tendency to consider TEVAR as a first-line solution for
      several thoracic aortic diseases.

PMID- 25596397
TI  - [Vasculitis - diagnostic and therapeutic advances].
AB  - Vasculitis is characterized by inflammation and necrosis of blood vessels walls.
      It represents a heterogeneous group of conditions, whose etiopathogenic
      mechanisms remain unclear. Although uncommon, with an annual incidence of 40-54
      cases per 1.000.000 persons, this is an important cause of multiorganic
      dysfunction and premature mortality. Depending on the affected vessels, it can
      cause diverse clinical presentations, which makes difficult its recognition. It
      is therefore a challenge for any clinician. This paper reviews the diagnostic and
      therapeutic advances of the most common forms of vasculitis, in order to optimize
      the approach and management of this clinical entity. We have conducted a search
      in Medline database on articles written in English, published for the last 10
      years using the keywords: vasculitis, epidemiology, classification, diagnosis and
      treatment. To minimize the impact of vasculitis it is essential an early
      diagnosis, allowing a timely institution of the appropriate treatment. The
      diagnosis depends on the integration of clinical, laboratory, imaging and
      histopathologic data. According to the clinical condition, it may be indicated
      the removal of the offending antigen, the treatment of the underlying disease or
      specific treatment of the primary vasculitis. The introduction of
      immunosuppressive therapy with glucocorticoids and cyclophosphamide has
      revolutionized the prognosis of these patients but, despite its efficacy, it is
      associated with frequent relapses and significant toxicity. The study of the
      pathogenesis has been providing more effective and safer diagnostic and
      therapeutic options, for example B-cell depleting agents, but additional studies
      are needed to confirm the potential of these alternatives. 

PMID- 25596396
TI  - [Persistence of left superior vena cava associated to esophageal atresia:
      presentation of 5 cases].
AB  - BACKGROUND: Esophageal atresia is known to be associated with a variety of
      additional congenital anomalies in multiple organ systems. Persistent left
      superior vena cava is one of the most common venous thoracic anomaly, occurring
      in about 0,3% of the population. The aim of this study was to characterize
      persistent left superior vena cava in infants treated in Hospital Dona Estefania
      with esophageal atresia. METHODS: A retrospective review of all children treated
      for esophageal atresia from January 2002 to December 2013 was undertaken. Charts
      were reviewed for gestational age, weight, type of atresia, preoperative
      echocardiogram, associated anomalies, surgical approach, eventual postoperative
      echocardiogram and angioresonance for the study of congenital venous anomaly.
      RESULTS: Of 107 children, five had persistent left superior vena cava. Of the
      five cases, one had prenatal diagnosis. Further investigation showed duodenal
      atresia in one, urologic malformation, coloboma and bilateral ear deformities in
      other. All five patients were operated on through right thoracotomy and primary
      anastomosis was performed after ligation of the trachea-esophageal fistula and
      underwent angioresonance to characterize the vascular anomaly. No operative or
      post-operative complications were registered. CONCLUSIONS: Inspite of the
      preoperative workup, the anomaly was only identified in one of the patients.
      Generally, diagnosis of PLSVC is incidentally found during routine left-sided
      central venous catheterizations. It is essential to characterize the pattern of
      cardiac venous return that places those patients at a risk for paradoxical
      embolic complications to the arterial system.

PMID- 25596398
TI  - [Endovascular management of an infectious and ruptured abdominal aortic aneurysm.
      Clinical report].
AB  - Infectious aneurysms are about 1-3% of all aneurysms of the infrarenal aorta. Its
      treatment is challenging and the best strategy is far from consensual. The
      authors report a case of a HIV + patient with multiple other co-morbidities,
      which was seen in the emergency department with fever and left back pain. These
      symptoms would prove to be in relation to a ruptured infectious aneurysm of the
      abdominal aorta. Facing this situation it was decided to select an endovascular
      technique with implantation of an aorto uni - iliac stent graft with a right-left
      femoro-femoral cross-over using a 8 mm PTFE graft and exclusion of the left
      common iliac . The patient didn't have any complication from the situation or the
      procedure, but died 18 months postoperatively because of a pneumonia caused by
      Pneumocystis jiroveci. Although it is not the ideal solution for the treatment of
      infectious elective aneurysms, we believe that endovascular treatment seems to be
      a viable option and should be taken into account in a subgroup of patients that
      for their co-morbidities are not good candidates for conventional surgery and for
      those in rupture, either as a bridge or as a final solution. 

PMID- 25596399
TI  - [Tracheocutaneous fistula after thyroidectomy].

PMID- 25596400
TI  - Synthesis, photophysical and antimicrobial activity of new water soluble ammonium
      quaternary benzanthrone in solution and in polylactide film.
AB  - The synthesis of a new cationic water soluble fluorescent 1-[(7-oxo-7H
      benzo[de]anthracen-3-ylcarbamoyl)-methyl]-triethylammonium chloride (B) has been
      described. Due to the presence of the quaternary amino group, the compound is
      soluble in water. Its photophysical characteristics in aqueous solution and
      organic solvents with different polarity have been determined using absorption
      and fluorescence spectroscopy. The photostability of compound B has been
      investigated in aqueous media. The newly synthesized compound has been tested in
      vitro for its antimicrobial activity against eight bacterial and two yeasts
      cultures. The results obtained suggest that the newly synthesized compound is
      effective in treating the relevant pathogens and is suitable in designing new
      effective antimicrobial preparations. The incorporation of the compound into thin
      polylactic acid film and its release into water solution has been also
      investigated. It was demonstrated that the compound released from the polymer
      polylactic acid matrix exhibited a prolonged good antibacterial activity. 

PMID- 25596401
TI  - Detecting associations of rare variants with common diseases: collapsing or
      haplotyping?
AB  - In recent years, a myriad of new statistical methods have been proposed for
      detecting associations of rare single-nucleotide variants (SNVs) with common
      diseases. These methods can be generally classified as 'collapsing' or
      'haplotyping' based. The former is the predominant class, composed of most of the
      rare variant association methods proposed to date. However, recent works have
      suggested that haplotyping-based methods may offer advantages and can even be
      more powerful than collapsing methods in certain situations. In this article, we
      review and compare collapsing- versus haplotyping-based methods/software in terms
      of both power and type I error. For collapsing methods, we consider three
      approaches: Combined Multivariate and Collapsing, Sequence Kernel Association
      Test and Family-Based Association Test (FBAT): the first two are population based
      and are among the most popular; the last test is family based, a modification
      from the popular FBAT to accommodate rare SNVs. For haplotyping-based methods, we
      include Logistic Bayesian Lasso (LBL) for population data and family-based LBL
      (famLBL) for family (trio) data. These two methods are selected, as they can be
      used to test association for specific rare and common haplotypes. Our results
      show that haplotype methods can be more powerful than collapsing methods if there
      are interacting SNVs leading to larger haplotype effects. Even if only common
      SNVs are genotyped, haplotype methods can still detect specific rare haplotypes
      that tag rare causal SNVs. As expected, family-based methods are robust, whereas
      population-based methods are susceptible, to population substructure. However,
      the population-based haplotype approach appears to have smaller inflation of type
      I error than its collapsing counterparts. 

PMID- 25596402
TI  - Hybrid treatment for thoracoabdominal aortic aneurysms in patients with Marfan
      syndrome.
AB  - Marfan syndrome is a heritable disorder of connective tissue leading to aortic
      aneurysms and other cardiovascular complications associated with reduced life
      expectancy. Although contemporary management of ascending aortic disease requires
      open surgical reconstruction, the combined retrograde visceral revascularization
      and endovascular exclusion (hybrid procedure) of entire thoracoabdominal aorta
      has been introduced for the management of descending thoracic and abdominal
      aortic pathology. The present experience reports 2 cases of thoracoabdominal
      aortic aneurysms, in Marfan patients, previously submitted to major
      cardiovascular surgical procedures, through a hybrid approach. 

PMID- 25596403
TI  - Nonvisualized type III endoleak masquerading as endotension: a case report.
AB  - Here, we describe a case of nonvisualized type III endoleak masquerading as
      endotension that was diagnosed by opening the aneurysm sac during surgery and
      successfully treated surgically. A 79-year-old man underwent endovascular
      aneurysm repair (EVAR) 4 years previously for an aneurysm that had enlarged
      gradually without endoleak. An open surgical operation was performed. The sac
      pressure was 132 mm Hg-similar to the preoperative systolic blood pressure-and
      nonpulsatile. After the aneurysm sac was opened without clamping the aorta, a
      type III endoleak from the suture point of the prosthetic endograft was detected.
      The prosthetic graft was successfully replaced with a Y-graft. The current
      findings suggest that nonvisualized type III endoleaks may be a potential cause
      of endotension. 

PMID- 25596404
TI  - Treatment of a high large extracranial carotid artery pseudoaneurysm from trauma
      using a Viabahn graft.
AB  - Blunt cerebrovascular injury has received much attention over the recent years;
      however, there is still considerable variability in terms of adequate criteria
      and treatment strategies. A case report was conducted to discuss the available
      literature in this disease process relative to the current practices at a level 1
      urban trauma center. Screening and treatment methods were discussed. A patient
      with a high cervical extracranial pseudoaneurysm of the internal carotid artery
      was treated successfully with endovascular techniques without future neurologic
      sequalae. 

PMID- 25596405
TI  - Repair of aortoenteric fistula secondary to graft placement for middle aortic
      syndrome.
AB  - When an aortoenteric fistula (AEF) arises secondary to suprarenal or more
      proximal aortic repair, mortality and the complexity of the surgery increases. We
      present the first reported case to our knowledge of a secondary AEF arising 13
      years after surgical repair of middle aortic syndrome. We performed the original
      surgery on a 22-year-old male who presented with hypertension and claudication by
      placing a Dacron prosthetic patch on the juxtarenal and infrarenal aorta,
      bilateral vein bypasses to the left and right renal artery, and a Dacron bypass
      to the proximal superior mesenteric artery. Thirteen years later, he presented
      with massive gastrointestinal bleeding and syncope. We performed a distal
      descending thoracic aortic rifampin-soaked bifurcated Dacron graft to the left
      renal artery and to a large meandering mesenteric artery followed by excision of
      all previous prosthetic graft and insertion of a rifampin-soaked tube graft from
      the distal descending thoracic aorta to the distal abdominal aorta with omental
      flap coverage. After a complicated postoperative course, he was discharged 2
      months later and remains on dialysis at his 6-month postoperative follow-up
      without evidence of recurrent infection. 

PMID- 25596406
TI  - Spontaneous rupture of an isolated iliac artery dissection in a young man because
      of cystic medial degeneration Erdheim-Gsell.
AB  - BACKGROUND: Rupture of isolated iliac artery dissections is a life-threatening
      event and has not been associated with cystic medial degeneration (CMD) Erdheim
      Gsell. METHODS: A young man presented to our emergency unit in a critical
      hemodynamic condition. Computed tomography scan feigned the rupture of an
      internal iliac artery. RESULTS: Surprisingly, we found a ruptured dissection of
      the common iliac artery during open surgery. Reconstruction was done by Dacron
      graft interposition between common and internal iliac artery and external iliac
      artery implantation into the graft. Histology revealed CMD. CONCLUSIONS:
      Spontaneous iliac artery dissection and rupture can be caused by CMD and requires
      immediate surgical intervention.

PMID- 25596407
TI  - Treatment of aneurysmal aberrant right subclavian artery with triple-barrel stent
      graft.
AB  - Aneurysmal evolution of an aberrant right subclavian artery (ARSA) is an
      operative indication. Endovascular treatment is a minimally invasive procedure,
      which offers good short-term and midterm results. We describe a case of a 9-cm
      diameter ARSA aneurysm in a symptomatic man, treated with the triple-barrel
      technique using a thoracic aortic stent graft combined with surgical and
      endovascular revascularization of the supra-aortic trunks. Postoperatively, the
      patient developed a type III endoleak which was covered. The triple-barrel
      technique has been a proposed treatment approach for complex aortic arch
      pathologies and remains a less invasive option when compared with open surgery. 

PMID- 25596408
TI  - Outcomes of neuroischemic wounds treated by a multidisciplinary amputation
      prevention service.
AB  - BACKGROUND: Multidisciplinary amputation prevention teams decrease the frequency
      of major amputations by increasing the use of revascularization procedures and
      minor amputations. The outcomes of wound healing, wound recurrence, and
      ambulatory status are assumed to be improved but are not routinely reported. This
      study investigates the midterm outcomes of neuroischemic wounds treated by our
      multidisciplinary team. METHODS: A retrospective review of patients with
      neuroischemic wounds treated at a single institution amputation prevention clinic
      from March 2012 to July 2013. Patient demographics, wound characteristics,
      procedural details, and clinical and functional outcomes were reviewed. Clinical
      end points under study included time to wound healing, reulceration rate, and
      ambulatory status. RESULTS: Over 16 months, there were 202 new patients and 1,355
      clinic visits. Ninety-one limbs from 89 patients were treated for complex
      neuroischemic wounds. In 67% (61 of 91) of limbs, wounds were present for >6
      weeks before referral. A history of previous revascularization was present in 39%
      (31 of 91), and 28% (22 of 91) had a previous minor amputation. Forty-one percent
      of wounds (38 of 91) were limited to the toes or the forefoot whereas 24% (22 of
      91) involved the hindfoot or ankle. A total of 151 podiatric and 86 vascular
      interventions were performed, with an equal distribution of endovascular and open
      revascularizations. Complete healing was observed for 59% of wounds (54 of 91)
      over the observation period (median follow up, 207 days; range 56-561 days), and
      the average time to full healing was 12 weeks. Hindfoot wounds were predictive of
      failure to heal (odds ratio, 0.21; P < 0.01; 95% confidence interval, 0.06-0.68).
      Nineteen percent of patients (17 of 91) developed a new wound in the ipsilateral
      leg during follow-up. Three major amputations were performed (2 below-knee
      amputation and 1 above-knee amputation) for a major/minor amputation ratio of
      0.06. Ambulatory status was preserved or improved in 74% (67 of 91) of patients.
      The 30-day readmission rate was 11%, which was lower than that observed (21%) in
      a contemporaneous but all-inclusive population of lower extremity
      revascularization procedures performed at our institution. CONCLUSIONS:
      Multidisciplinary limb salvage teams effectively heal wounds and maintain
      ambulatory status in patients with limb-threatening neuroischemic wounds. Patient
      specific factors, such as hindfoot or ankle wounds, can adversely influence the
      outcome. Even with aggressive care, healing can be prolonged and a substantial
      proportion of patients can be expected to have a recurrence, making subsequent
      surveillance mandatory. Our data also suggest that a coordinated amputation
      prevention program may help to minimize hospital readmissions in this high-risk
      population.

PMID- 25596409
TI  - Hybrid treatment of lower limb critical ischemia in a patient with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic
      disease, which affects primarily small-sized vessels, arterioles, venules, and
      capillaries in the cardiovascular system. Less often, medium-sized vessels are
      affected, and large-sized vessels are affected rarely. We report an unusual case
      of a 52-year-old female patient with SLE under treatment and multileveled
      arterial obstructive disease of the lower limb, who presented with critical limb
      ischemia. The patient was treated using a hybrid endovascular and open
      revascularization procedure, on the basis of the clinical picture of the patient,
      the angiographic findings, and the experience of our department. Our aim is not
      only to highlight the rarity of the clinical picture but also to make useful
      conclusions regarding the proper management for such unusual cases. Given the
      fact that there are no guidelines, we present the treatment strategy selected for
      our patient and discuss our results. 

PMID- 25596410
TI  - Loss of body fat and associated decrease in leptin in early lactation are related
      to shorter duration of postpartum anovulation in healthy US women.
AB  - BACKGROUND: The mechanisms regulating postpartum anovulation (PPA) are not well
      understood, although poor nutritional status and "intense" breastfeeding
      behaviors are associated with longer durations. OBJECTIVES: This study was
      designed primarily to investigate the hypothesis that higher body fat and leptin
      concentrations are related to shorter PPA in healthy, lactating US women.
      Nutrient intake, breastfeeding behaviors, prolactin, and insulin levels were also
      evaluated. METHODS: Fasting serum was collected during the third trimester of
      pregnancy, at 2 and 4 weeks postpartum, and every 4 weeks until the occurrence of
      the first postpartum menses. Body composition and breastfeeding behaviors were
      assessed at the same times postpartum. Women (n = 13) were categorized based on
      initial percentage body fat and timing of first postpartum menses. RESULTS: There
      were no consistent relationships between body composition, leptin, or
      breastfeeding behaviors and duration of PPA. However, there was an interaction (P
      = .005) between ovulation group and time on adiposity; earlier ovulating women
      had less percentage body fat in early lactation than did later ovulating women.
      There was also an interaction (P = .1) between ovulation group and time
      postpartum on leptin, such that leptin concentrations tended to be greater in
      later than earlier ovulating groups beginning at 12 weeks postpartum. CONCLUSION:
      In summary, although baseline percentage body fat and leptin were not related to
      duration of PPA, fertility returned earlier in women who lost greater percentage
      body fat during the early postpartum period.

PMID- 25596411
TI  - Factors influencing exclusive breastfeeding at 4 months postpartum in a sample of
      urban Hispanic mothers in Kentucky.
AB  - BACKGROUND: Although Hispanic mothers in the United States have slightly higher
      rates of breastfeeding initiation than the national average, they are more likely
      to supplement with formula. OBJECTIVES: To describe infant feeding decisions in a
      sample of 72 urban Hispanic mothers and assess whether demographic and personal
      factors influence exclusive breastfeeding (EBF) status at 4 months postpartum.
      METHODS: The study was longitudinal and included assessments during pregnancy, in
      the hospital following childbirth, and monthly up to 4 months following birth.
      RESULTS: Nearly all of the 72 mothers were breastfeeding at discharge after the
      birth of their infant (94%); half of these were EBF. By 2 months postpartum, the
      rate of EBF had declined to 26%, dropping to 22% by 4 months. Significant
      predictors of EBF status at 4 months included the baseline indicator for mother's
      partner as the most important person in life (adjusted odds ratio [AOR], 5.42;
      95% confidence interval [CI], 1.03-28.66) and breastfeeding self-efficacy score
      at 1 month (AOR, 1.20; 95% CI, 1.07-1.34). CONCLUSION: These findings have
      particular relevance in this population, given the high rate of breastfeeding
      initiation coupled with breastfeeding self-efficacy being a modifiable factor.
      Support during pregnancy and postpartum, including consultation with a lactation
      consultant, may increase the self-efficacy of EBF in this low-income population,
      leading to higher rates of extended EBF among Hispanics.

PMID- 25596412
TI  - Non-steroidal anti-inflammatory drugs and venous thromboembolism.

PMID- 25596414
TI  - Excipient pharmacokinetics and profiling.
AB  - Novel pharmaceutical excipients, and new derivatives of currently used
      excipients, are new chemical entities and as such have to go through extensive
      pharmacokinetic and toxicologic evaluations before they can be approved for use
      in pharmaceutical products. The high cost of these safety studies, long
      development timelines and risks of failure have hampered development of new
      excipients and drug delivery systems. Various, relatively simple, methods are
      used for prediction of pharmacokinetic properties of new drug candidates based on
      their physicochemical properties. Similar methods can be applied to predict
      pharmacokinetic and ADME properties of new excipients. Simple methods, like the
      Rule-of-Five and the Biopharmaceutics Classification System, can be applied for
      early prediction of pharmacokinetic and ADME properties of new excipients and
      drug delivery systems although the aims can be different. While the objectives in
      new drug development are to maximize drug bioavailability and pharmacologic
      response the objectives in new excipient development can be reduced excipient
      bioavailability and enhanced rate of elimination. Here pharmacokinetic properties
      of some currently used excipients are reviewed and shown how some of the simple
      methods used to predict drug-like properties can be applied to predict desired
      properties of novel excipients and drug delivery systems. 

PMID- 25596415
TI  - High speed electrospinning for scaled-up production of amorphous solid dispersion
      of itraconazole.
AB  - High speed electrospinning (HSES), compatible with pharmaceutical industry, was
      used to demonstrate the viability of the preparation of drug-loaded polymer
      nanofibers with radically higher productivity than the known single-needle
      electrospinning (SNES) setup. Poorly water-soluble itraconazole (ITRA) was
      formulated with PVPVA64 matrix polymer using four different solvent-based methods
      such as HSES, SNES, spray drying (SD) and film casting (FC). The formulations
      were assessed in terms of improvement in the dissolution rate of ITRA (using a
      "tapped basket" dissolution configuration) and analysed by SEM, DSC and XRPD.
      Despite the significantly increased productivity of HSES, the obtained morphology
      was very similar to the SNES nanofibrous material. ITRA transformed into an
      amorphous form, according to the DSC and XRPD results, in most cases except the
      FC samples. The limited dissolution of crystalline ITRA could be highly improved:
      fast dissolution occurred (>90% within 10min) in the cases of both (the scaled-up
      and the single-needle) types of electrospun fibers, while the improvement in the
      dissolution rate of the spray-dried microspheres was significantly lower.
      Production of amorphous solid dispersions (ASDs) with the HSES system proved to
      be flexibly scalable and easy to integrate into a continuous pharmaceutical
      manufacturing line, which opens new routes for the development of industrially
      relevant nanopharmaceuticals. 

PMID- 25596416
TI  - Controlled release of indomethacin from alginate-poloxamer-silicon carbide
      composites decrease in-vitro inflammation.
AB  - Composites of biomorphic silicon carbides (bioSiCs) and hydrogels are proposed in
      order to obtain materials able to load and release poor soluble drugs with
      application in bone pathologies therapy. Hydrogels composed by alginate and
      poloxamer were loaded with indomethacin, incorporated into the ceramics and
      crosslinked. The indomethacin release profile is dependent on the microstructure
      of the bioSiC selected. The loaded oak and sapelli bioSiCs composites have
      adequate release profiles to promote the decreasing of the secretion of pro
      inflammatory cytokines in LPS stimulated macrophages, showing stronger anti
      inflammatory effects than pine bioSiC composites. The released indomethacin is
      able to modulate the degradation of chondrocytes extracellular matrix and promote
      the formation of new collagen by osteoarthritic chondrocytes. Particles derived
      from mechanical wear of biomorphic silicon carbides do not show high toxicity,
      being similar to the zirconia particles. 

PMID- 25596413
TI  - Value of systolic pulmonary arterial pressure as a prognostic factor of death in
      the systemic sclerosis EUSTAR population.
AB  - OBJECTIVE: The aim of this study was to assess the prognostic value of systolic
      pulmonary artery pressure (sPAP) estimated by echocardiography in the
      multinational European League Against Rheumatism Scleroderma Trial and Research
      (EUSTAR) cohort. METHODS: Data for patients with echocardiography documented
      between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR
      database. Stepwise forward multivariable statistical Cox pulmonary hypertension
      analysis was used to examine the independent effect on survival of selected
      variables. RESULTS: Based on our selection criteria, 1476 patients were included
      in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d.
      13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d.
      1.2, median 1.9). Taking index sPAP of <30 mmHg as reference, the hazard ratio
      (HR) for death was 1.67 (95% CI 0.92, 2.96) if the index sPAP was between 30 and
      36 mmHg, 2.37 (95% CI 1.14, 4.93) for sPAP between 36 and 40 mmHg, 3.72 (95% CI
      1.61, 8.60) for sPAP between 40 and 50 mmHg and 9.75 (95% CI 4.98, 19.09) if sPAP
      was >50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for
      carbon monoxide (DLCO) were independently associated with the risk of death [HR
      1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively].
      sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91,
      4.78) for sPAP >=36 mmHg. CONCLUSION: An estimated sPAP >36 mmHg at baseline
      echocardiography was significantly and independently associated with reduced
      survival, regardless of the presence of pulmonary hypertension based on right
      heart catheterization.

PMID- 25596417
TI  - Application of circular dichroism and magnetic circular dichroism for assessing
      biopharmaceuticals formulations photo-stability and small ligands binding
      properties.
AB  - Synchrotron radiation circular dichroism (SRCD) is a powerful tool for photo
      stability assessment of proteins. Recently our research has been interested in
      applying SRCD to develop screening methodologies for accelerated photo-stability
      assessment of monoclonal antibody formulations. Despite it was proven to be
      reliable and applicable within a wide range of salts and excipients containing
      solutions, the presence of far-UV (<260nm) strong absorbing species (e.g., sodium
      chloride, histidine, arginine) in common formulations completely prevent the
      analysis. Herein, we propose a new method based on CD coupled with magnetic CD
      (MCD) to address the problem and offer an additional versatile tool for
      monitoring the photo-stability. This is done by assessing the stability of the
      samples by looking at the near-UV band, as well as giving insights in the
      denaturation mechanism. We applied this method to four mAbs formulations and
      correlated the results with dynamic light scattering data. Finally, we applied
      MCD in ligand interaction to key proteins such as lysozyme, comparing the human
      with the hen enzyme in the binding of N,N',N''-triacetylchitotriose. 

PMID- 25596418
TI  - The effect of steam sterilization on recombinant spider silk particles.
AB  - In this work, the recombinant spider silk protein eADF4(C16) was used to
      fabricate particles in the submicron range using a micromixing method.
      Furthermore, particles in the micrometer range were produced using an ultrasonic
      atomizer system. Both particle species were manufactured by an all-aqueous
      process. The submicroparticles were 332 nm in average diameter, whereas 6.70 MUm
      was the median size of the microparticles. Both particle groups showed a
      spherical shape and exhibited high beta-sheet content in secondary structure.
      Submicro- and microparticles were subsequently steam sterilized and investigated
      with respect to particle size, secondary structure and thermal stability.
      Sterilization temperature and time were increased to assess the thermal stability
      of eADF4(C16) particles. Actually, particles remained stable and their properties
      did not change even after autoclaving at 134 degrees C. Both, the untreated and
      the autoclaved submicroparticles showed no overt cytotoxicity on human dermal
      fibroblasts after incubation for 72 h. The eADF4(C16) particles were already
      loaded with proteins and small molecules in previous studies. With that, we can
      provide a highly promising parenteral drug delivery system based on a defined
      polypeptide carrier, manufactured with an all-aqueous process and being fully
      sterilizable.

PMID- 25596419
TI  - Scaffolds, cells, biologics: At the crossroads of musculoskeletal repair.

PMID- 25596421
TI  - KCC2-mediated regulation of respiration-related rhythmic activity during
      postnatal development in mouse medulla oblongata.
AB  - GABA acts as inhibitory neurotransmitter in the adult central nervous system but
      as excitatory neurotransmitter during early postnatal development. This shift in
      GABA's action from excitation to inhibition is caused by a decrease in
      intracellular chloride concentration ([Cl(-)]i), which in turn is caused by
      changes in the relative expression levels of the K(+)-Cl(-) co-transporter (KCC2)
      and the Na(+), K(+)-2Cl(-) co-transporter (NKCC1) proteins. Previous studies have
      used slices containing the medullary pre-Botzinger complex (pre-BotC) to record
      respiration-related rhythmic activity (RRA) from the hypoglossal nucleus (12 N).
      The role of GABAergic transmission in the regulation of medullary RRA neonatally,
      however, is yet to be determined. Here, we examined how GABA and chloride co
      transporters contribute to RRA during development in the 12 N where inspiratory
      neurons reside. We recorded extracellular RRA in medullary slices obtained from
      postnatal day (P) 0-7 mice. RRA was induced by soaking slices in artificial
      cerebrospinal fluid (aCSF) containing 8mM-K(+). Application of GABA significantly
      increased the frequency of RRA after P3, whereas application of a KCC2 blocker (R
      (+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-indenyl-5
      yl)oxy]acetic acid (DIOA)) significantly decreased the frequency of RRA after P1.
      In addition, dense KCC2 immunolabeling was seen in the superior longitudinalis
      (SL) of the 12 N, which is responsible for retraction of the tongue, from P0 and
      P7. These results indicate that GABA administration can increase RRA frequency
      during the first week following birth. This in turn suggests that decreasing [Cl(
      )]i levels caused by increasing KCC2 levels in the 12 N could play important
      roles in regulating the frequency of RRA during development.

PMID- 25596422
TI  - Exceeding chance level by chance: The caveat of theoretical chance levels in
      brain signal classification and statistical assessment of decoding accuracy.
AB  - Machine learning techniques are increasingly used in neuroscience to classify
      brain signals. Decoding performance is reflected by how much the classification
      results depart from the rate achieved by purely random classification. In a 2
      class or 4-class classification problem, the chance levels are thus 50% or 25%
      respectively. However, such thresholds hold for an infinite number of data
      samples but not for small data sets. While this limitation is widely recognized
      in the machine learning field, it is unfortunately sometimes still overlooked or
      ignored in the emerging field of brain signal classification. Incidentally, this
      field is often faced with the difficulty of low sample size. In this study we
      demonstrate how applying signal classification to Gaussian random signals can
      yield decoding accuracies of up to 70% or higher in two-class decoding with small
      sample sets. Most importantly, we provide a thorough quantification of the
      severity and the parameters affecting this limitation using simulations in which
      we manipulate sample size, class number, cross-validation parameters (k-fold,
      leave-one-out and repetition number) and classifier type (Linear-Discriminant
      Analysis, Naive Bayesian and Support Vector Machine). In addition to raising a
      red flag of caution, we illustrate the use of analytical and empirical solutions
      (binomial formula and permutation tests) that tackle the problem by providing
      statistical significance levels (p-values) for the decoding accuracy, taking
      sample size into account. Finally, we illustrate the relevance of our simulations
      and statistical tests on real brain data by assessing noise-level classifications
      in Magnetoencephalography (MEG) and intracranial EEG (iEEG) baseline recordings. 

PMID- 25596423
TI  - Anti-neuroinflammatory effects of DPTP, a novel synthetic clovamide derivative in
      in vitro and in vivo model of neuroinflammation.
AB  - Neuroinflammation is one of the critical pathological mechanisms influencing
      various neurodegenerative disorders. Most of the neurodegenerative diseases
      involve over-activation of microglial cells contributing to the demise of
      neurons. The objective of the current study is to evaluate the anti-inflammatory
      effect of novel synthetic clovamide derivative on the suppression of microglial
      activation in an in vitro and in vivo model of neuroinflammation. We have used
      lipopolysaccharide (LPS) to induce an inflammatory response in murine BV-2
      microglial cells. Molecular tools like immunocytochemistry and immunoblotting
      were used to study the activity of novel synthetic clovamide derivative to
      inhibit inflammation induced by LPS in microglial cells. In in vivo experiments,
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mouse model of
      neuroinflammation was developed to investigate the anti-neuroinflammatory effects
      of DPTP [3-(3,4-Dihydroxy-phenyl)-2-[4-(3-trifluoromethylphenyl)-but-2
      enoylamino]-propionic acid methyl ester]. DPTP was observed to reduce the
      proinflammatory response in BV-2 cells induced by LPS. Further investigation
      revealed that DPTP attenuated phosphorylation of c-Jun N-terminal kinase (JNK)
      and extracellular signal-regulated kinase (ERK), which was accompanied by a
      decrease in nuclear translocation of nuclear factor-kappaB (NF-kappaB) in LPS
      treated BV2 microglia. Moreover, prophylactic treatment with DPTP (20mg/kg) for 7
      days suppressed MPTP induced glial activation and behavioral impairment. Overall,
      our findings suggested that, DPTP exerts anti-neuroinflammatory effects against
      activated microglia in an in vitro and in vivo model and hence might be a
      promising therapeutic agent for alleviating the evolvement of neurodegenerative
      diseases associated with microglial activation. 

PMID- 25596420
TI  - Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal
      Alzheimer's disease.
AB  - INTRODUCTION: The purpose of this study was to study the effect of donepezil on
      the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). METHODS: A
      double-blind, randomized, placebo-controlled parallel group design using
      donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent
      two brain magnetic resonance imaging scans (baseline and final visit). The
      primary efficacy outcome was the annualized percentage change (APC) of total
      hippocampal volume (left + right) measured by an automated segmentation method.
      RESULTS: Two-hundred and sixteen only subjects were randomized across 28 French
      expert clinical sites. In the per protocol population (placebo = 92 and donepezil
      = 82), the donepezil group exhibited a significant reduced rate of hippocampal
      atrophy (APC = -1.89%) compared with the placebo group (APC = -3.47%), P < .001.
      There was no significant difference in neuropsychological performance between
      treatment groups. DISCUSSION: A 45% reduction of rate of hippocampal atrophy was
      observed in prodromal AD following 1 year of treatment with donepezil compared
      with placebo.

PMID- 25596424
TI  - Role of Natural Killer Cells in Intravenous Immunoglobulin-Induced Graft-versus
      Host Disease Inhibition in NOD/LtSz-scidIL2rg(-/-) (NSG) Mice.
AB  - Although clinical studies have yet to demonstrate clearly the use of intravenous
      immunoglobulin (IVIG) for prevention of graft-versus-host disease (GVHD), their
      effective use in a xenogeneic mouse model has been demonstrated. We aimed to
      determine the mechanism of action by which IVIG contributes to GVHD prevention in
      a xenogeneic mouse model. NOD/LtSz-scidIL2rg(-/-) (NSG) mice were used for our
      xenogeneic mouse model of GVHD. Sublethally irradiated NSG mice were injected
      with human peripheral blood mononuclear cells (huPBMCs) and treated weekly with
      PBS or 50 mg IVIG. Incidence of GVHD and survival were noted, along with analysis
      of cell subsets proliferation in the peripheral blood. Weekly IVIG treatment
      resulted in a robust and consistent proliferation of human natural killer cells
      that were activated, as demonstrated by their cytotoxicity against K562 target
      cells. IVIG treatment did not inhibit GVHD when huPBMCs were depleted in natural
      killer (NK) cells, strongly suggesting that this NK cell expansion was required
      for the IVIG-mediated prevention of GVHD in our mouse model. Moreover, inhibition
      of T cell activation by either cyclosporine A (CsA) or monoclonal antihuman CD3
      antibodies abolished the IVIG-induced NK cell expansion. In conclusion, IVIG
      treatment induces NK cell proliferation, which is essential for IVIG-mediated
      protection of GVHD in our mouse model. Furthermore, activated T cells are
      mandatory for effective IVIG-induced NK cell proliferation. These results shed
      light on a new mechanism of action of IVIG and could explain why the efficacy of
      IVIG in preventing GVHD in a clinical setting, where patients receive CsA, has
      never been undoubtedly demonstrated. 

PMID- 25596425
TI  - Identification and molecular characterization of a peritrophin-like gene,
      involved in the antibacterial response in Chinese mitten crab, Eriocheir
      sinensis.
AB  - Peritrophin was first isolated from insect peritrophic membrane (PM) and was
      thought to protect insects from invasion of microorganisms and to stimulate
      digestion of food. In this study, a peritrophin-like gene (EsPT) was obtained
      from Eriocheir sinensis. The full length cDNA of EsPT was 1232 bp, which
      contained 1005 bp ORF encoding a protein of 334 amino acids, including a 22 amino
      acid signal peptide, and 3 conserved chitin binding type 2 domains (ChtBD2)
      characterized by having a 6-cysteine motif. Phylogenetic analysis showed that
      EsPT was clustered together with 2 insect peritrophin-44-like proteins (MdP44L
      from Musca domestica and CcP44L from Ceratitis capitata), an insect chitin
      binding peritrophin-A domain containing protein (CfPT from Coptotermes
      formosanus) and a crustacean peritrophin (MnPT from Macrobrachium nipponense).
      Tissue distribution analysis revealed that EsPT was mainly expressed in
      hepatopancreas, intestine and hemocytes. The expression of EsPT is regulated by
      lipopolysaccharide, peptidoglycan, Staphylococcus aureus, Vibrio parahaemolyticus
      and Aeromonas hydrophila challenge. The recombinant EsPT could bind to different
      microbes, and enhanced the clearance of V. parahaemolyticus in vivo. In crabs,
      silencing of EsPT by siRNA suppressed the elimination of V. parahaemolyticus and
      increasing number of bacteria, finally upregulated the expression of anti
      lipopolysaccharide factor (ALF) and clip domain serine proteases (cSP). The
      results might indicate that EsPT was involved in the anti-bacterial innate
      immunity of crabs. 

PMID- 25596426
TI  - Ribosomal initiation complex-driven changes in the stability and dynamics of
      initiation factor 2 regulate the fidelity of translation initiation.
AB  - Joining of the large, 50S, ribosomal subunit to the small, 30S, ribosomal subunit
      initiation complex (IC) during bacterial translation initiation is catalyzed by
      the initiation factor (IF) IF2. Because the rate of subunit joining is coupled to
      the IF, transfer RNA (tRNA), and mRNA codon compositions of the 30S IC, the
      subunit joining reaction functions as a kinetic checkpoint that regulates the
      fidelity of translation initiation. Recent structural studies suggest that the
      conformational dynamics of the IF2.tRNA sub-complex forming on the intersubunit
      surface of the 30S IC may play a significant role in the mechanisms that couple
      the rate of subunit joining to the IF, tRNA, and codon compositions of the 30S
      IC. To test this hypothesis, we have developed a single-molecule fluorescence
      resonance energy transfer signal between IF2 and tRNA that has enabled us to
      monitor the conformational dynamics of the IF2.tRNA sub-complex across a series
      of 30S ICs. Our results demonstrate that 30S ICs undergoing rapid subunit joining
      display a high affinity for IF2 and an IF2.tRNA sub-complex that primarily
      samples a single conformation. In contrast, 30S ICs that undergo slower subunit
      joining exhibit a decreased affinity for IF2 and/or a change in the
      conformational dynamics of the IF2.tRNA sub-complex. These results strongly
      suggest that 30S IC-driven changes in the stability of IF2 and the conformational
      dynamics of the IF2.tRNA sub-complex regulate the efficiency and fidelity of
      subunit joining during translation initiation. 

PMID- 25596428
TI  - Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation,
      while potently inhibiting estradiol-3-O-glucuronidation.
AB  - This in vitro study investigates the effects of diethylstilbestrol (DES), a
      widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O)
      glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP
      glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O
      glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that
      the inhibition follows a competitive inhibition mechanism, with the Ki value of
      2.1+/-0.3MUM, which is less than the possible in vivo level. In contrast to the
      inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O
      glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In
      the presence of DES (0-6.25MUM), Km values for E2-17-O-glucuronidation are
      located in the range of 7.2-7.4MUM, while Vmax values range from 0.38 to
      1.54nmol/min/mg. The mechanism behind the activation in HLM is further
      demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4
      in catalyzing E2-17-O-glucuronidation. The presence of DES (2MUM) can elevate
      Vmax from 0.016 to 0.81nmol/min/mg, while lifting Km in a much lesser extent from
      4.4 to 11MUM. Activation of E2-17-O-glucuronidation is well described by a two
      binding site model, with KA, alpha, and beta values of 0.077+/-0.18MUM, 3.3+/-1.1
      and 104+/-56, respectively. However, diverse effects of DES towards E2-3/17-O
      glucuronidation are not observed in liver microsomes from several common
      experimental animals. In summary, this study issues new potential toxic
      mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully
      accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. 

PMID- 25596429
TI  - Role of p53-fibrinolytic system cross-talk in the regulation of quartz-induced
      lung injury.
AB  - Silica is the major component of airborne dust generated by wind, manufacturing
      and/or demolition. Chronic occupational inhalation of silica dust containing
      crystalline quartz is by far the predominant form of silicosis in humans.
      Silicosis is a progressive lung disease that typically arises after a very long
      latency and is a major occupational concern with no known effective treatment.
      The mechanism of silicosis is not clearly understood. However, silicosis is
      associated with increased cell death, expression of redox enzymes and pro
      fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and
      disruption of alveolar fibrinolysis is often associated with both acute and
      chronic lung injuries, we explored whether p53-mediated changes in the urokinase
      type plasminogen activator (uPA) system contributes to silica-induced lung
      injury. We further sought to determine whether caveolin-1 scaffolding domain
      peptide (CSP), which inhibits p53 expression, mitigates lung injury associated
      with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice
      exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of
      uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA
      expression and prevents AEC apoptosis by suppressing p53, which is otherwise
      induced in mice exposed to silica. The process involves CSP-mediated inhibition
      of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C
      (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations
      suggest that changes in the p53-uPA fibrinolytic system cross-talk contribute to
      lung injury caused by inhalation of silica dust containing crystalline quartz and
      is protected by CSP by targeting this pathway. 

PMID- 25596430
TI  - MAPK pathway activation by chronic lead-exposure increases vascular reactivity
      through oxidative stress/cyclooxygenase-2-dependent pathways.
AB  - Chronic exposure to low lead concentration produces hypertension; however, the
      underlying mechanisms remain unclear. We analyzed the role of oxidative stress,
      cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced
      by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10
      MUg/100g; subsequent doses: 0.125MUg/100g, intramuscular, 30days) and cultured
      aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated
      with lead (20MUg/dL) were used. Lead blood levels of treated rats attained 21.7+/
      2.38MUg/dL. Lead exposure increased systolic blood pressure and aortic ring
      contractile response to phenylephrine, reduced acetylcholine-induced relaxation
      and did not affect sodium nitroprusside relaxation. Endothelium removal and L
      NAME left-shifted the response to phenylephrine more in untreated than in lead
      treated rats. Apocynin and indomethacin decreased more the response to
      phenylephrine in treated than in untreated rats. Aortic protein expression of
      gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In
      cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase
      activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2
      and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors
      normalized superoxide anion production, NADPH oxidase activity and mRNA levels of
      NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways
      abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead
      activation of the MAPK signaling pathways activates inflammatory proteins such as
      NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to
      vascular dysfunction as an underlying mechanisms for lead-induced hypertension. 

PMID- 25596427
TI  - Mitochondrial quality control: Easy come, easy go.
AB  - "Friends come and go but enemies accumulate." - Arthur Bloch Mitochondrial
      networks in eukaryotic cells are maintained via regular cycles of degradation and
      biogenesis. These complex processes function in concert with one another to
      eliminate dysfunctional mitochondria in a specific and targeted manner and
      coordinate the biogenesis of new organelles. This review covers the two aspects
      of mitochondrial turnover, focusing on the main pathways and mechanisms involved.
      The review also summarizes the current methods and techniques for analyzing
      mitochondrial turnover in vivo and in vitro, from the whole animal proteome level
      to the level of single organelle.

PMID- 25596431
TI  - Topological, functional, and dynamic properties of the protein interaction
      networks rewired by benzo(a)pyrene.
AB  - Benzo(a)pyrene is a common environmental and foodborne pollutant that has been
      identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene
      has been extensively reported, its precise molecular mechanisms and the influence
      on system-level protein networks are not well understood. To investigate the
      system-level influence of benzo(a)pyrene on protein interactions and regulatory
      networks, a benzo(a)pyrene-rewired protein interaction network was constructed
      based on 769 key proteins derived from more than 500 literature reports. The
      protein interaction network rewired by benzo(a)pyrene was a scale-free, highly
      connected biological system. Ten modules were identified, and 25 signaling
      pathways were enriched, most of which belong to the human diseases category,
      especially cancer and infectious disease. In addition, two lung-specific and two
      liver-specific pathways were identified. Three pathways were specific in short
      and medium-term networks (<48h), and five pathways were enriched only in the
      medium-term network (6h-48h). Finally, the expression of linker genes in the
      network was validated by Western blotting. These findings establish the overall,
      tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and
      provide insights into the biological effects and molecular mechanisms of action
      of benzo(a)pyrene. 

PMID- 25596432
TI  - Intranasal immunization with an adenovirus vaccine protects guinea pigs from
      Ebola virus transmission by infected animals.
AB  - Experimental Ebola virus (EBOV) vaccines have previously been shown to protect
      animals against a high dose intramuscular (IM) challenge, which is seen as a
      stringent challenge model. However, the protective efficacy against other modes
      of infection, such as contact with infectious hosts, is unknown. Using a
      previously established EBOV transmission animal model, we evaluated the efficacy
      of an adenovirus-based EBOV vaccine given to guinea pigs (gps) 4weeks before
      direct contact with untreated, infectious animals. Prior vaccination resulted in
      robust levels of EBOV-specific antibodies and conferred complete protection in
      gps. These results support the use of vaccines to prevent EBOV transmission
      between hosts. 

PMID- 25596433
TI  - Cerebral revascularization: which patients should be bypassed and which patients
      should be passed by?

PMID- 25596434
TI  - A bump in the road more than the tip of the iceberg.

PMID- 25596435
TI  - Olfactory Groove Meningiomaas.

PMID- 25596436
TI  - Social determinants of malaria and health care seeking patterns among rice
      farming and pastoral communities in Kilosa District in central Tanzania.
AB  - This study was carried out to understand the role social determinants and health
      seeking behavior among rice farming and pastoral communities in Kilosa District
      in central Tanzania. The study involved four villages; two with rice farming
      communities while the other two with pastoral communities. In each village, heads
      of households or their spouses were interviewed to seek information on
      livelihoods activities, knowledge and practices on malaria and its preventions. A
      total of 471 individuals (males=38.9%; females=61.1%) were interviewed. Only
      23.5% of the respondents had adequate knowledge on malaria. Fifty-six percent of
      the respondents could not associate any livelihood activity with malaria
      transmission. Majority (79%) of the respondents believed that most of fevers were
      due to malaria; this was higher among the pastoral (81.7%) than rice farming
      communities (76.1%) (p=0.038). Cases of fever were significantly higher in
      households with non-educated (31.2%) than educated respondents (21.5%). Women
      experienced significantly more episodes of fever than men (p<0.001). Of the total
      of 2606 individuals living in the households, 26.9% were reported to have had
      fever in the previous three months. Fever was reported more frequently among
      pastoral than rice farming communities (p<0.01). Of those who had fever, 36.6%
      were clinically diagnosed with malaria and 22.9% were confirmed to be infected
      with malaria. A combination of fever+convulsions or joint pains+headache was most
      frequently perceived to be malaria. Treatment seeking frequency differed by the
      size of the household and between rice farming and pastoral communities (p=0.05).
      In conclusion, education, sex, availability of health care facility and
      livelihood practices were the major social determinants that influence malaria
      acquisition and care seeking pattern in central Tanzania. Appropriate public
      health promotion should be designed to address the links of livelihoods and
      malaria transmission among rural farming communities in an ecohealth approach.

PMID- 25596437
TI  - Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain
      mitochondria from young-adult and old rats.
AB  - Chronic and systemic treatment of rodents with rotenone, a classical inhibitor of
      mitochondrial respiratory complex I, results in neurochemical, behavioral, and
      neuropathological features of Parkinson's disease. The aim of the present study
      was to evaluate whether brain mitochondria from old rats (24 months old) would be
      more susceptible to rotenone-induced inhibition of oxygen consumption and
      increased generation of H2O2 than mitochondria from young-adult rats (3-4 months
      old). Isolated brain mitochondria were incubated in the presence of different
      rotenone concentrations (5, 10, and 100nM), and oxygen consumption and H2O2
      production were measured during respiratory states 3 (ADP-stimulated respiration)
      and 4 (resting respiration). Respiratory state 3 and citrate synthase activity
      were significantly lower in mitochondria from old rats. Mitochondria from young
      adult and old rats showed similar sensitivity to rotenone-induced inhibition of
      oxygen consumption. Similarly, H2O2 production rates by both types of
      mitochondria were dose-dependently stimulated to the same extent by increasing
      concentrations of rotenone. We conclude that rotenone exerts similar effects on
      oxygen consumption and H2O2 production by isolated brain mitochondria from young
      adult and old rats. Therefore, aging does not increase the mitochondrial H2O2
      generation in response to complex I inhibition. 

PMID- 25596438
TI  - Activation of D1-like dopamine receptors increases the NMDA-induced gain
      modulation through a PKA-dependent pathway in the premotor nucleus of adult zebra
      finches.
AB  - Interaction between dopamine (DA) and N-methyl-d-aspartate (NMDA) in the brain
      plays an important role in learning and memory. In the songbirds, the premotor
      robust nucleus of the arcopallium (RA) receives excitatory glutamatergic inputs
      from the high vocal center (HVC) and lateral magnocellular nucleus of the
      anterior nidopallium (LMAN), as well as dopaminergic inputs mostly from the
      periaqueductal gray (PAG) and ventral tegmental area (VTA). In zebra finch, DA
      potentiates the excitability of projection neurons in the RA through activation
      of D1-like dopamine receptors (D1 receptors). The relationship between D1
      receptors and NMDA in the RA projection neurons is essentially unknown. Our
      previous work showed that NMDA can induce gain modulation in the RA projection
      neurons. Here, using the whole-cell current-clamp recording from brain slices of
      male zebra finches, we observed whether D1 receptors regulate the NMDA-induced
      gain modulation in the RA projection neurons. Our results showed that activation
      of D1 receptors further increased the slope (gain) of the firing frequency
      injected current (f-I) relationship induced by NMDA in the RA projection neurons.
      Blocking D1 receptors had no effect on the NMDA-induced gain modulation in the RA
      projection neurons. The enhanced effects of D1 receptors agonists were blocked by
      protein kinase A (PKA) inhibitors. Our results suggest that activation of D1
      receptors can increase the NMDA-induced gain modulation through a PKA-dependent
      pathway. 

PMID- 25596439
TI  - Transcutaneous spinal DC stimulation reduces pain sensitivity in humans.
AB  - Non-invasive approaches to pain management are needed to manage patient pain
      escalation and to providing sufficient pain relief. Here, we evaluate the
      potential of transcutaneous spinal direct current stimulation (tsDCS) to modulate
      pain sensitivity to electrical stimuli and mechanical pinpricks in 24 healthy
      subjects in a sham-controlled, single-blind study. Pain ratings to mechanical
      pinpricks and electrical stimuli were recorded prior to and at three time points
      (0, 30, and 60min) following 15min of anodal tsDCS (2.5mA, "active" electrode
      centered over the T11 spinous process, return electrode on the left posterior
      shoulder). Pain ratings to the pinpricks of the highest forces tested (128, 256,
      512mN) were reduced at 30min and 60min following anodal tsDCS. These findings
      demonstrate that pain sensitivity in healthy subjects can be suppressed by anodal
      tsDCS and suggest that tsDCS may provide a non-invasive tool to manage
      mechanically-induced pain. 

PMID- 25596440
TI  - A new rat model of neuropathic pain: complete brachial plexus avulsion.
AB  - Brachial plexus avulsion (BPA) is one of the major injuries in motor vehicle
      accidents and may result in neuropathic pain. Accumulating evidence suggests that
      30-80% of BPA developed neuropathic pain in human. In our study, complete
      brachial plexus avulsion (C5-T1) rats model leads to the results that 37.5% of
      rats had long-lasting (up to 6 months) mechanical allodynia and cold allodynia.
      We observed the activation of astrocyte and microglial in cervical spinal cord
      after BPA. Complete brachial plexus avulsion mimics human nerve root traction
      injury following traffic accidents. The complete BPA rat model approach human
      injuries and can be used for further investigations. 

PMID- 25596441
TI  - Glutamate and GABA concentration changes in the globus pallidus internus of
      Parkinson's patients during performance of implicit and declarative memory tasks:
      a report of two subjects.
AB  - The basal ganglia, typically associated with motor function, are involved in
      human cognitive processes, as demonstrated in behavioral, lesion, and noninvasive
      functional neuroimaging studies. Here we report task-contingent changes in
      concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric
      acid (GABA) in the globus pallidus internus (GPi) of two patients with
      Parkinson's disease undergoing deep brain stimulation surgery by utilizing in
      vivo microdialysis measurements during performance of implicit and declarative
      memory tasks. Performance of an implicit memory task (weather prediction task
      WPT) was associated with increased levels of glutamate and GABA in the GPi
      compared to their concentrations at baseline. On the other hand, performance of a
      declarative memory task (verbal learning task-VLT) was associated with decreased
      levels of glutamate and GABA in GPi compared to baseline during the encoding and
      immediate recall phase with less conclusive results during the delayed recall
      phase. These results are in line with hypothesized changes in these
      neurotransmitter levels: an increase of excitatory (Glu) input from subthalamic
      nucleus (STN) to GPi during implicit memory task performance and a decrease of
      inhibitory inputs (GABA) from globus pallidus externus (GPe) and striatum to GPi
      during declarative memory performance. Consistent with our previous report on in
      vivo neurotransmitter changes during tasks in STN, these data provide
      corroborative evidence for the direct involvement of basal ganglia in cognitive
      functions and complements our model of the functional circuitry of basal ganglia
      in the healthy and Parkinson's disease affected brain. 

PMID- 25596442
TI  - Cyclic AMP inhibits neuromuscular junction maturation mediated by intracellular
      Ca2+.
AB  - The neuromuscular junction (NMJ) is established through initial contact of motor
      neuron axon with a skeletal muscle cell and the subsequent synaptic maturation.
      Previous studies have shown that cyclic AMP (cAMP) enhanced spinal neurons'
      survival and growth but inhibited synaptogenesis. Here, we find that elevating
      intracellular cAMP level of presynaptic neurons prevented NMJs from maturation
      both physiologically and morphologically. Importantly, cytosolic Ca(2+) is
      essential for the inhibitory effects of cAMP on NMJ maturation. We show that
      depletion of intracellular Ca(2+) store, rather than extracellular Ca(2+),
      abolished the cAMP-dependent inhibition of synaptic maturation. Taken together,
      we demonstrate that Ca(2+) released from intracellular Ca(2+) stores regulates
      neurotrophic actions on NMJ maturation. 

PMID- 25596443
TI  - Increased interhemispheric functional connectivity in college students with non
      clinical depressive symptoms in resting state.
AB  - The underlying neural basis of non-clinical depressive symptoms (nCDSs) remains
      unclear. Interhemispheric functional connectivity has been suggested as one of
      the most robust characteristics of brain's intrinsic functional architecture.
      Here, we investigated the functional connectivity between homotopic points in the
      brain using the voxel-mirrored homotopic connectivity (VMHC) approach. We
      performed VMHC analysis on resting-state functional magnetic resonance imaging
      (rs-fMRI) data from 17 individuals with nCDSs and 20 healthy controls (HCs) who
      were enrolled from a sample of 1105 college students. We found increased VMHCs in
      the bilateral posterior cerebellum and fusiform gyrus in nCDSs subjects compared
      with HCs. Furthermore, receiver operating characteristic (ROC) curves indicated
      that VMHC values in the posterior cerebellum lobes could use to differente nCDSs
      from HCs [area under the curve (AUC), 0.756; p<0.01]. We suggest increased VMHCs
      indicate a possible compensatory mechanism involved in the pathophysiology of
      nCDSs. VMHC values of the posterior cerebellum lobes might serve as a reliable
      biomarker for identifying nCDSs. 

PMID- 25596444
TI  - Supramarginal activity in interoceptive attention tasks.
AB  - Interoceptive (feelings from inside organs) attention/awareness (IAA) is a body
      related aspect of cognition that pursues homeostasis by detecting afferent
      signals, and there are practices aimed at focusing one's attention and awareness
      towards such feelings inside one's own body. There is a claim that these
      practices improve health which is one reason that neural correlates of such
      practices and IAA in general have been investigated in previous imaging studies.
      In several of these studies which used subjects with no or limited experience in
      IAA practices there was a report of supramarginal (SM) activity during IAA tasks,
      but the role of SM in IAA remain unclear. We first investigated if we could find
      similar results in novices, and if this activity is sensitive to the designated
      body part in the IAA task. We further investigated if these regions would be
      similarly recruited in subjects with extensive experience of IAA tasks while
      comparing results with a group of age and gender matched novices. Results in the
      novices replicated that of previous studies, and we showed this is the same for
      IAA tasks regarding two different parts of the body. Group comparison results
      showed opposite profiles of SM activation for the two groups; novices showed
      activation and the experts showed deactivation of the SM. The results suggest
      that novices recruit SM during IAA possibly due to lack of experience in those
      tasks but this could be alleviated for performing IAA as illustrated by
      activation profile in experts. 

PMID- 25596445
TI  - High frequency transcutaneous electrical nerve stimulation with diphenidol
      administration results in an additive antiallodynic effect in rats following
      chronic constriction injury.
AB  - The impact of coadministration of transcutaneous electrical nerve stimulation
      (TENS) and diphenidol is not well established. Here we estimated the effects of
      diphenidol in combination with TENS on mechanical allodynia and tumor necrosis
      factor-alpha (TNF-alpha) expression. Using an animal chronic constriction injury
      (CCI) model, the rat was estimated for evidence of mechanical sensitivity via von
      Frey hair stimulation and TNF-alpha expression in the sciatic nerve using the
      ELISA assay. High frequency (100Hz) TENS or intraperitoneal injection of
      diphenidol (2.0MUmol/kg) was applied daily, starting on postoperative day 1
      (POD1) and lasting for the next 13 days. We demonstrated that both high frequency
      TENS and diphenidol groups had an increase in mechanical withdrawal thresholds of
      60%. Coadministration of high frequency TENS and diphenidol gives better results
      of paw withdrawal thresholds in comparison with high frequency TENS alone or
      diphenidol alone. Both diphenidol and coadministration of high frequency TENS
      with diphenidol groups showed a significant reduction of the TNF-alpha level
      compared with the CCI or HFS group (P<0.05) in the sciatic nerve on POD7, whereas
      the CCI or high frequency TENS group exhibited a higher TNF-alpha level than the
      sham group (P<0.05). Our resulting data revealed that diphenidol alone, high
      frequency TENS alone, and the combination produced a reduction of neuropathic
      allodynia. Both diphenidol and the combination of diphenidol with high frequency
      TENS inhibited TNF-alpha expression. A moderately effective dose of diphenidol
      appeared to have an additive effect with high frequency TENS. Therefore,
      multidisciplinary treatments could be considered for this kind of mechanical
      allodynia. 

PMID- 25596446
TI  - Crossover study of the effect of coffee consumption on simulated laparoscopy
      skills.
AB  - AIMS: To observe the effect of caffeine on performing laparoscopic skills in
      novices in a simulated setting. BACKGROUND: Coffee is consumed almost
      ubiquitously by surgeons not just as a stimulant but also socially in the well
      rested individual. It's therefore worth investigating its potentially negative
      effect on performance of surgical skills as it is known that coffee has
      psychomotor effects. METHODS: This is a single-blind crossover study in which 31
      novices were tested under three different conditions: decaffeinated, 100 mg
      caffeine and 200 mg caffeine. Candidates were asked to perform 3 repetitions of
      task 3, 6, 7 and 8 using the Lap MentorTM (Simbionix((r))). Outcomes measured
      were completion time, accuracy, number of movements and total path length. The
      candidates were crossed over to the other caffeine doses on a different day.
      RESULTS: 20 candidates completed the study, mean age 21.3 years, with 10 males
      and 10 females. Candidates performed tasks 7 and 8 faster in the decaffeinated
      group than the caffeinated groups with significant differences between
      decaffeinated and 100 mg caffeine (p-value = 0.001, 0.019 respectively) and
      decaffeinated and 200 mg in task 8(p-value = 0.042). Total path length was
      significantly less in the decaffeinated group in tasks 7 and 8 and total number
      of movements was less in tasks 3, 7 and 8. CONCLUSION: Caffeine had no marked
      effect on accuracy, but had a negative effect on task economy (hand movements,
      total path length and completion time).

PMID- 25596447
TI  - Perioperative antiviral therapy improves safety in patients with hepatitis B
      related HCC following hepatectomy.
AB  - INTRODUCTION: Hepatectomies may exacerbate chronic hepatitis B in patients with
      high hepatitis B viral (HBV) DNA levels, and could result in hepatic
      insufficiency. Antiviral treatment is effective for suppressing HBV virus loads.
      This study investigated whether perioperative antiviral therapy is warranted for
      resection of hepatocellular carcinoma (HCC) with concurrent HBV infections.
      METHODS: Patients with HBV-related HCC (n = 112) who underwent major liver
      resection were retrospectively divided into two groups based on treatment with
      perioperative antiviral therapy (antiviral group) (n = 72) or absence of
      antiviral treatment (control group) (n = 40). RESULTS: Exacerbation of chronic
      hepatitis B occurred in 6 patients of the control group (15.0%). The prevalence
      of hepatic insufficiency in the antiviral group and control group were 1.4%
      (1/72) and 12.5% (5/40), respectively (p < 0.05). Five of them (4.5%) developed
      hepatic encephalopathy and 3 of them (2.7%) developed hepatorenal syndrome. The
      control group had significantly higher morbidity (75.0% vs. 34.7%, p < 0.01) than
      the antiviral group. The control group had significantly higher levels of
      postoperative alanine aminotransferase (ALT) and serum bilirubin than the
      antiviral group. CONCLUSION: Perioperative antiviral treatment improves patient
      safety by decreasing morbidity and speeding recovery of postoperative liver
      function for HBV-related major HCC resection.

PMID- 25596448
TI  - ER stress response in NG108-15 cells involves upregulation of syntaxin 5
      expression and reduced amyloid beta peptide secretion.
AB  - Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of
      neurodegenerative diseases such as Alzheimer's disease (AD). We previously showed
      that manipulation of the ER-Golgi-soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (ER-Golgi SNARE) syntaxin 5 (Syx5) causes changes in
      Golgi morphology and the processing of AD-related proteins. To understand the
      pathophysiologic significance of these phenomena, we examined whether the
      expression of Syx5 is altered by ER stress. De novo synthesis of ER-Golgi SNARE
      Syx5 and Bet1 was induced by various ER stressors. Elevated expression of Syx5
      and Bet1 was associated with increased levels of these proteins in vesicular
      components, including ER-Golgi-intermediate-compartment/vesicular tubular
      clusters. In addition, ER stress diminished amyloid beta (Abeta) peptide
      secretion. Knockdown of Syx5 expression enhanced the secretion of Abeta peptides
      under condition without ER stress. Moreover, diminished Abeta peptide secretion
      resulting from ER stress was significantly reversed by Syx5 knockdown. These
      findings suggest that Syx5 plays important roles in beta-amyloid precursor
      protein processing and in the ER stress response that precedes apoptotic cell
      death and may be involved in the crosstalk between these two pathways. 

PMID- 25596449
TI  - ATP-dependent molecular chaperones in plastids--More complex than expected.
AB  - Plastids are a class of essential plant cell organelles comprising photosynthetic
      chloroplasts of green tissues, starch-storing amyloplasts of roots and tubers or
      the colorful pigment-storing chromoplasts of petals and fruits. They express a
      few genes encoded on their organellar genome, called plastome, but import most of
      their proteins from the cytosol. The import into plastids, the folding of freshly
      translated or imported proteins, the degradation or renaturation of denatured and
      entangled proteins, and the quality-control of newly folded proteins all require
      the action of molecular chaperones. Members of all four major families of ATP
      dependent molecular chaperones (chaperonin/Cpn60, Hsp70, Hsp90 and Hsp100
      families) have been identified in plastids from unicellular algae to higher
      plants. This review aims not only at giving an overview of the most current
      insights into the general and conserved functions of these plastid chaperones,
      but also into their specific plastid functions. Given that chloroplasts harbor an
      extreme environment that cycles between reduced and oxidized states, that has to
      deal with reactive oxygen species and is highly reactive to environmental and
      developmental signals, it can be presumed that plastid chaperones have evolved a
      plethora of specific functions some of which are just about to be discovered.
      Here, the most urgent questions that remain unsolved are discussed, and guidance
      for future research on plastid chaperones is given. This article is part of a
      Special Issue entitled: Chloroplast Biogenesis. 

PMID- 25596450
TI  - Plastid sigma factors: Their individual functions and regulation in
      transcription.
AB  - Sigma factors are the predominant factors involved in transcription regulation in
      bacteria. These factors can recruit the core RNA polymerase to promoters with
      specific DNA sequences and initiate gene transcription. The plastids of higher
      plants originating from an ancestral cyanobacterial endosymbiont also contain
      sigma factors that are encoded by a small family of nuclear genes. Although all
      plastid sigma factors contain sequences conserved in bacterial sigma factors, a
      considerable number of distinct traits have been acquired during evolution. The
      present review summarises recent advances concerning the regulation of the
      structure, function and activity of plastid sigma factors since their discovery
      nearly 40 years ago. We highlight the specialised roles and overlapping redundant
      functions of plastid sigma factors according to their promoter selectivity. We
      also focus on the mechanisms that modulate the activity of sigma factors to
      optimise plastid function in response to developmental cues and environmental
      signals. This article is part of a Special Issue entitled: Chloroplast
      Biogenesis.

PMID- 25596451
TI  - Pragmatism, mathematical models, and the scientific ideal of prediction and
      control.
AB  - Mathematical models are often held to be valuable, if not necessary, for theories
      and explanations in the quantitative analysis of behavior. The present review
      suggests that mathematical models primarily derived from the observation of
      functional relations do indeed contribute to the scientific value of theories and
      explanations, even though the final form of the models appears to be highly
      abstract. However, mathematical models not primarily so derived risk being
      essentialist in character, based on a particular view of formal causation. Such
      models invite less effective and frequently mentalistic theories and explanations
      of behavior. Models may be evaluated in terms of both (a) the verbal processes
      responsible for their origin and development and (b) the prediction and control
      engendered by the theories and explanations that incorporate the models, however
      indirect or abstract that prediction and control may be. Overall, the present
      review suggests that technological application and theoretical contemplation may
      be usefully viewed as continuous and overlapping forms of scientific activity,
      rather than dichotomous and mutually exclusive. 

PMID- 25596452
TI  - The role of fractalkine (CX3CL1) in regulation of CD4(+) cell migration to the
      central nervous system in patients with relapsing-remitting multiple sclerosis.
AB  - Fractalkine (CX3CL1) levels are increased in the cerebrospinal fluid (CSF) of
      patients with clinically isolated syndrome (CIS), as well as in the CSF and serum
      samples from patients with relapsing-remitting multiple sclerosis (RRMS). A
      higher percentage of circulating CD4(+) T-cells expressed its surface receptor
      (CX3CR1) and intracellular adhesion molecule (ICAM-1) in RRMS patients in
      comparison to healthy controls (HCs). The CX3CR1(+)ICAM-1(+)CD4(+) T-cells are
      enriched in the CSF of the RRMS patients. In vitro migration studies revealed
      that CD4(+) T-cells, which migrated toward a CX3CL1 gradient, expressed higher
      levels of ICAM-1 than non-migrating cells. CX3CL1 significantly increased IFN
      gamma and TNF-alpha gene expression and IFN-gamma secretion by CD4(+) T-cells
      derived from the RRMS patients. CX3CL1 upregulated ICAM-1 expression on the
      surface of RRMS patient-derived but not HC-derived CD4(+) T-cells. Thus, CX3CL1
      induces recruitment of CX3CR1(+)ICAM-1(+)CD4(+) T-cells into the central nervous
      system (CNS) during the early inflammatory response in MS. 

PMID- 25596454
TI  - Targeting human CD2 by the monoclonal antibody CB.219 reduces intestinal
      inflammation in a humanized transfer colitis model.
AB  - The cell adhesion molecule CD2 facilitates antigen-independent T-cell activation
      and CD2 deficiency or blockade reduces intestinal inflammation in murine models.
      We here aimed to evaluate the therapeutic potential of monoclonal antibodies
      (mAb) specific for human CD2 in colitis treatment. Transfer colitis induced by
      naive CD4(+) T cells expressing human CD2 was treated with anti-human CD2 mAb.
      The mAb CB.219 protected from severe colitis in a preventive treatment regimen,
      while therapeutic treatment ameliorated intestinal inflammation. Diminished
      intestinal tissue damage was paralleled by a profound suppression of lamina
      propria lymphocytes to produce pro-inflammatory cytokines and tumor necrosis
      factor alpha as well as the neutrophil chemoattractant CXC motif ligand 1 and the
      CC chemokine ligand 3. Furthermore, infiltration with macrophages and T cells was
      low. Thus, reduced intestinal inflammation in our humanized colitis model by
      targeting CD2 on T cells with the mAb CB.219 suggests a novel approach for
      colitis treatment. 

PMID- 25596453
TI  - Clonal and constricted T cell repertoire in Common Variable Immune Deficiency.
AB  - We used high throughput sequencing to examine the structure and composition of
      the T cell receptor beta chain in Common Variable Immune Deficiency (CVID).
      TCRbeta CDR3 regions were amplified and sequenced from genomic DNA of 44 adult
      CVID subjects and 22 healthy adults, using a high-throughput multiplex PCR. CVID
      TCRs had significantly less junctional diversity, fewer n-nucleotide insertions
      and deletions, and completely lacked a population of highly modified TCRs, with
      13 or more V-gene nucleotide deletions, seen in healthy controls. The CVID CDR3
      sequences were significantly more clonal than control DNA, and displayed unique V
      gene usage. Despite reduced junctional diversity, increased clonality and similar
      infectious exposures, DNA of CVID subjects shared fewer TCR sequences as compared
      to controls. These abnormalities are pervasive, found in out-of-frame sequences
      and thus independent of selection and were not associated with specific clinical
      complications. These data support an inherent T cell defect in CVID.

PMID- 25596455
TI  - A functional inflammasome activation assay differentiates patients with
      pathogenic NLRP3 mutations and symptomatic patients with low penetrance variants.
AB  - Cryopyrin-associated periodic syndromes (CAPS) are characterized by recurrent
      episodes of systemic inflammation caused by mutations in the NLRP3 gene. Besides
      confirmed pathogenic NLRP3 mutations, patients with CAPS-like symptoms frequently
      show low penetrance variants in NLRP3. The disease relevance of these variants is
      inconsistent. In this study, we investigated if an inflammasome activation assay
      differentiates between patients with confirmed pathogenic CAPS mutations,
      patients with low penetrance NLRP3 variants (V198M and Q703K) and healthy
      controls. The release of mature IL-1beta, IL-18, and caspase-1 into cell culture
      supernatants after 4h of inflammasome stimulation was significantly increased in
      patients with confirmed pathogenic CAPS mutations compared to low penetrance
      NLRP3 variants and controls. IL-1beta secretion in CAPS patients correlated with
      disease severity. This inflammasome activation assay differentiates between
      autoinflammation patients with confirmed pathogenic CAPS mutations and patients
      with low penetrance NLRP3 variants, and points towards alternative
      pathophysiological mechanisms in low penetrance NLRP3 variants. 

PMID- 25596456
TI  - Protective efficacy and immune responses induced by a DNA vaccine encoding codon
      optimized PPA1 against Photobacterium damselae subsp. piscicida in Japanese
      flounder.
AB  - Photobacterium damselae subsp. piscicida (Pdp) kills many cultured marine fish.
      As it evolves resistance to existing vaccines, new vaccines are needed. PPA1 is a
      major antigenic protein of Pdp. Here, DNA vaccines encoding wild-type PPA1
      (pPPA1(wt)) and codon-optimized PPA1 (pPPA1(opt)) were constructed and tested
      against Pdp in Japanese flounder. The mRNA levels of the two antigenic genes at
      the vaccination site were not different, but the protein level was significantly
      higher in the pPPA1(opt)-vaccinated fish. In addition, after a bacterial
      challenge, the levels of interleukin (IL)-1beta, IL-6 and IFN-gamma mRNA
      significantly increased in the pPPA1(opt)-vaccinated fish but not in the
      pPPA1(wt)-vaccinated fish. The relative percent survival (RPS) after the
      challenge was higher in the pPPA1(opt)-vaccinated fish (90.9) than in the
      pPPA1(wt)-vaccinated fish (69.2). At the early stage of the infection after the
      challenge, the number of viable Pdp in the spleen was significantly lower in the
      pPPA1(opt)-vaccinated fish than in the pPPA1(wt)-vaccinated fish. These data show
      that codon-optimized DNA vaccine pPPA1(opt) had a strong immunogenicity and
      conferred protective efficacy against Pdp infection in Japanese flounder. 

PMID- 25596457
TI  - Chimeric hepatitis B virus (HBV)/hepatitis C virus (HCV) subviral envelope
      particles induce efficient anti-HCV antibody production in animals pre-immunized
      with HBV vaccine.
AB  - The development of an effective, affordable prophylactic vaccine against
      hepatitis C virus (HCV) remains a medical priority. The recently described
      chimeric HBV-HCV subviral envelope particles could potentially be used for this
      purpose, as they could be produced by industrial procedures adapted from those
      established for the hepatitis B virus (HBV) vaccine. We show here, in an animal
      model, that pre-existing immunity acquired through HBV vaccination does not
      influence the immunogenicity of the HCV E2 protein presented by these chimeric
      particles. Thus, these chimeric HBV-HCV subviral envelope particles could
      potentially be used as a booster in individuals previously vaccinated against
      HBV, to induce protective immunity to HCV. 

PMID- 25596458
TI  - Protective efficacy of a DNA vaccine construct encoding the VP2 gene of
      infectious bursal disease and a truncated HSP70 of Mycobacterium tuberculosis in
      chickens.
AB  - Infectious bursal disease (IBD) is an acute, infectious, immunosuppressive
      disease affecting young chicken worldwide. The etiological agent IBD virus (IBDV)
      is a double stranded RNA virus with outer capsid protein VP2 of IBDV is the major
      antigenic determinant capable of inducing neutralizing antibody. DNA vaccines
      encoding VP2 has been extensively studied achieving only partial protection.
      However, the efficacy of DNA vaccines against IBDV can be augmented by choosing a
      potential molecular adjuvant. The goal of the present study is to evaluate the
      immune response and protective efficacy of a DNA vaccine encoding the C-terminal
      domain of the heat shock protein 70 (cHSP70) of Mycobacterium tuberculosis gene
      genetically fused with the full length VP2 gene of IBDV (pCIVP2-cHSP70) in
      comparison to a 'DNA prime-protein boost' approach and a DNA vaccine encoding the
      VP2 gene (pCIVP2) alone. The results indicate that both pCIVP2-cHSP70 and 'DNA
      prime-protein boost' elicited humoral as well as cellular immune responses.
      Chickens in the pCIVP2-cHSP70 and 'DNA prime-protein boost' groups developed
      significantly higher levels of ELISA titer to IBDV antigen compared to the group
      immunized with pCIVP2 alone (p<0.01). However, significantly higher levels of
      lymphocyte proliferative response, IL-12 and IFN-gamma production were found in
      the pCIVP2-cHSP70 group compared to 'DNA prime-protein boost' group.
      Additionally, chickens immunized with pCIVP2-cHSP70 and 'DNA prime-protein boost'
      vaccines were completely protected against the vvIBDV whereas pCIVP2 DNA vaccine
      alone was able to protect only 70%. These findings suggest that the truncated C
      terminal HSP70 mediated DNA vaccine genetically fused with the VP2 gene construct
      stimulated both humoral and cell mediated immune responses and conferred complete
      protection against IBDV. This novel strategy is perhaps a seminal concept in
      utilizing HSP70 as an adjuvant molecule to elicit an immune response against IBD
      affecting chickens. 

PMID- 25596459
TI  - Effectiveness of acellular pertussis vaccine in a routine immunization program: a
      multicenter, case-control study in Japan.
AB  - In 2008, the number of pertussis cases increased substantially among Japanese
      adolescents, despite high coverage with acellular pertussis vaccine (DTaP). This
      study examined the effectiveness of DTaP vaccine in the routine immunization
      program in Japan. Between April 2009 and October 2012, we conducted a
      multicenter, case-control study, and compared the history of DTaP vaccination
      between 55 newly diagnosed pertussis cases and 90 age- and sex-matched controls.
      DTaP vaccine history was obtained by a self-administered questionnaire completed
      by their parents or guardians. Logistic regression models were used to calculate
      odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for
      development of pertussis. DTaP vaccination of >=1 dose revealed a significantly
      lower OR for pertussis (OR=0.20, 95%CI, 0.04-0.97), and the OR of complete
      vaccination (4 doses) was 0.22 (0.04-1.05). Even after limiting subjects to those
      whose vaccination status could be confirmed by the immunization records, the
      negative associations were observed. The decreasing ORs of 4-dose vaccinees
      remained, even among subjects who had received the fourth dose >=9.2 years
      earlier (OR=0.11, 95%CI, 0.01-1.02). In conclusion, DTaP vaccination had a
      preventive effect for pertussis. Effectiveness was observed even 9 or more years
      after the final dose. 

PMID- 25596461
TI  - Insect vectors as drivers of plant virus emergence.

PMID- 25596460
TI  - Intussusception risk after RotaTeq vaccination: evaluation from worldwide
      spontaneous reporting data using a self-controlled case series approach.
AB  - The increased risk of intussusception after vaccination with the rhesus-human
      reassortant rotavirus vaccine Rotashield led to its withdrawal in 2005. We assess
      the risk of intussusception following the pentavalent rotavirus vaccine (RV5) on
      the basis of worldwide reports to the manufacturer up to May 2014, using a self
      controlled case series. The method had to be modified to account for the under
      reporting, a specific feature of pharmacovigilance spontaneous reports. The risk
      of intussusception occurring in either of the 0- to 2-day, 3- to 7-day or 8- to
      14-day risk periods, was compared to the risk in the 15- to 30-day period. A
      total of 502 cases occurring 0-30 days after a vaccine dose were studied,
      including 188 cases after the first dose, 190 cases after the second dose, and
      124 cases after the third dose. The incidence risk ratio relative to the control
      period was highest for the 3- to 7-day period and equal to 3.45 (95% CI 1.84
      6.55), 1.63 (0.86-3.13) and 1.73 (0.86-3.51) after the first, second and third
      dose, respectively. Rotavirus vaccination with RV5 increases the risk of
      intussusception 3-7 days following vaccination, mainly after the first dose and
      marginally after the second and third doses. The risk is small and restricted to
      a short time window. It does not outweigh the benefit of the vaccination, but
      parents of vaccinated infants should be informed in order to react appropriately
      to the first symptoms. With appropriate assumptions about the reporting rate,
      spontaneous reports of adverse events after vaccination can be studied to
      evaluate vaccine safety. 

PMID- 25596462
TI  - Affective responses to emotional words are boosted in communicative situations.
AB  - Emotional verbal messages are typically encountered in meaningful contexts, for
      instance, during face-to-face communication in social situations. Yet, they are
      often investigated by confronting single participants with isolated words on a
      computer screen, thus potentially lacking ecological validity. In the present
      study we recorded event-related brain potentials (ERPs) during emotional word
      processing in communicative situations provided by videos of a speaker, assuming
      that emotion effects should be augmented by the presence of a speaker addressing
      the listener. Indeed, compared to non-communicative situations or isolated word
      processing, emotion effects were more pronounced, started earlier and lasted
      longer in communicative situations. Furthermore, while the brain responded most
      strongly to negative words when presented in isolation, a positivity bias with
      more pronounced emotion effects for positive words was observed in communicative
      situations. These findings demonstrate that communicative situations--in which
      verbal emotions are typically encountered--strongly enhance emotion effects,
      underlining the importance of social and meaningful contexts in processing
      emotional and verbal messages.

PMID- 25596465
TI  - Alpha B-crystallin prevents ventricular arrhythmia by attenuating inflammation
      and oxidative stress in rat with autoimmune myocarditis.

PMID- 25596464
TI  - Effects of morcellation of uterine smooth muscle tumor of uncertain malignant
      potential and endometrial stromal sarcoma: case series and recommendations for
      clinical practice.
AB  - STUDY OBJECTIVE: To assess the consequences of inadvertent morcellation of
      uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or
      endometrial stromal sarcomas (ESSs) and to investigate the findings of surgical
      re-exploration procedures including the frequency and nature of disease
      dissemination. DESIGN: A retrospective chart review from January 1, 1999, to
      October 31, 2014. Cases were identified by cross-referencing the terms
      "morcellate" and "morcellation" with the terms "smooth muscle tumor of uncertain
      malignant potential," "STUMP," "endometrial stromal sarcoma," and "low grade
      endometrial stromal sarcoma" within the University of Michigan electronic medical
      record. One additional patient was identified at St. Joseph Mercy Hospital using
      the pathology database with keywords "uterine sarcoma" (Canadian Task Force
      classification III). SETTING: University of Michigan, Ann Arbor, MI, and St.
      Joseph Mercy Hospital, Ann Arbor, MI. PATIENTS: Patients who underwent
      hysterectomy or myomectomy with morcellation and were subsequently found to have
      a STUMP or ESS on pathologic review. INTERVENTIONS: None, retrospective chart
      review. MEASUREMENTS AND MAIN RESULTS: Eight patients were identified who
      underwent morcellation and were subsequently found to have a STUMP or ESS. Five
      patients underwent power morcellation, 2 patients underwent hand morcellation,
      and 1 patient underwent laparoscopic bivalving. Seven patients had a secondary
      surgical assessment 6 to 19.2 weeks after their initial procedure. Five patients
      were found to have benign implants comprised of myometrium or endometrium, 1
      patient had widespread malignant implants, and 1 patient had no evidence of
      peritoneal implants. One patient underwent power morcellation within a specimen
      bag after supracervical hysterectomy. This patient had evidence of benign
      implants at the time of her re-exploration procedure. All patients who underwent
      surgical re-exploration are living. The patient with malignant implants has been
      maintained on megestrol for more than 8 years without disease recurrence. The
      remaining patients have no evidence of disease with follow-up ranging from 2.8 to
      35.1 months. CONCLUSION: Surgical re-exploration procedures after morcellation of
      a uterine STUMP or ESS have a high likelihood of detecting peritoneal implants,
      which can be benign or malignant.

PMID- 25596466
TI  - Progression of cardiac involvement in patients with limb-girdle type 2 and Becker
      muscular dystrophies: a 9-year follow-up study.
AB  - AIM: To assess the degree and progression of cardiac involvement in patients with
      limb-girdle type 2 (LGMD2) and Becker muscular dystrophies (BMD). METHODS: A
      follow-up study of 100 LGMD2 (types A-L) and 30 BMD patients assessed by
      electrocardiogram (ECG) and echocardiography, supplemented by Holter-monitoring
      at follow-up. RESULTS: After a median of 8.9years (range 0.4-13.7), twelve
      patients had died: LGMD2 (n=10, mean age 61+/-11years), BMD (n=2, age 43 and
      45years). Of the remaining 118 patients, 89 completed follow-up: LGMD2 (n=64, age
      48+/-13years) and BMD (n=25, age 40+/-13years). In BMD, LVEF decreased from 60%
      (10-62) to 50% (10-64), p=0.02 corresponding to a one percentage drop annually.
      Among patients with LGMD2, LVEF decreased significantly in patients with LGMD
      type 2I (n=28) from 59% (15-72) to 55% (20-61), p=0.03, i.e. a 0.4 percentage
      drop annually, and LVEF<=50% was associated with increased mortality in this
      subgroup. In LGMD2E, 3/5 patients (60%) at baseline and 4/5 (80%) at follow-up
      had LVEF<=50%. ECG abnormalities were non-progressive in BMD and in all subgroups
      of LGMD2. SVT and NSVT were present in both groups: BMD (3/14 (21%) and (2/14
      (14%)), LGMD2 (16/51 (31%) and 8/51 (16%)), respectively, all asymptomatic.
      CONCLUSION: LVEF decreased significantly in patients with BMD and LGMD2I, and the
      majority of patients with LGMD2E had left ventricular systolic dysfunction. This
      study emphasizes the need for tailored regular cardiac assessments according to
      molecular diagnosis with special focus on BMD and LGMD types 2I and 2E.

PMID- 25596467
TI  - Medicare claims for myocardial infarction as primary vs. secondary diagnosis.

PMID- 25596469
TI  - Sustained blood pressure lowering effect of twice daily remote ischemic
      conditioning sessions in a normotensive/prehypertensive subject.

PMID- 25596468
TI  - Early invasive strategy in high-risk acute coronary syndrome without ST-segment
      elevation. The Sisca randomized trial.
AB  - BACKGROUND: The optimal therapeutic strategy for patients with high-risk acute
      coronary syndrome without ST-segment elevation (NSTE-ACS) remains unclear.
      OBJECTIVE: Our aim was to compare the effectiveness of an early invasive strategy
      and a delayed invasive strategy in the management of high-risk NSTE-ACS patients.
      METHODS: This randomized clinical trial in a primarily pre-hospital setting
      enrolled patients with chest pain, electrocardiographic criteria for an NSTE-ACS,
      and at least one criterion of severity (ESC criterion or TIMI score >5). Patients
      were randomized to either an early invasive strategy (tirofiban infusion and
      coronary angiography within 6h) or delayed invasive strategy (as per guidelines
      and physician discretion; coronary angiography within 6h was not advised). The
      primary endpoint was the cumulative incidence of deaths, myocardial infarctions,
      or urgent revascularizations at 30days of follow-up. Secondary endpoints were
      failure of delayed management, length of hospital stay and long-term mortality.
      RESULTS: Between January 2007 and February 2010, 170 patients were enrolled. The
      cumulative incidence of adverse outcomes was significantly lower for early
      invasive than delayed management (2% [95% CI 0-9] vs. 24% [95% CI 16-35], p<10(
      4)). Delayed management failed in 24% of cases. The length of hospital stay was
      significantly shorter in patients undergoing angioplasty or treated with
      tirofiban within 6h (p=0.0003). Long-term mortality was 16% in both arms after a
      median follow-up of 4.1years. CONCLUSION: An early invasive strategy reduced
      major adverse cardiac events in patients with high-risk NSTE-ACS. Early
      angiography or tirofiban (GP IIb/IIIa inhibitor) infusion proved necessary in a
      quarter of patients assigned to delayed management.

PMID- 25596471
TI  - Elevated heart rate at 24-36h after admission and in-hospital mortality in acute
      in non-arrhythmic heart failure.
AB  - BACKGROUND: Elevated resting heart rate is associated with worse outcomes in
      chronic heart failure (HF) but little is known about its prognostic impact in
      acute setting. The main aim of the present study was to examine the relationship
      between resting heart rate obtained 24-36h after admission for acute non
      arrhythmic HF and in-hospital mortality. METHODS AND RESULTS: We examined the
      association of heart rate with in-hospital mortality in a cohort of 712 patients
      admitted for acute HF. None of the patients had significant arrhythmias, required
      invasive ventilation, or presented with acute coronary syndrome or primary
      valvular disease. Forty patients (5.6%) died during the hospital stay. Those
      patients were significantly older (78+/-9 vs. 72+/-12years; p=0.0021), had higher
      heart rate (92+/-22 vs. 78+/-18bpm; p<0.0001), NT pro-BNP (p=0.0005), creatinine
      (p=0.023), were often diabetics (p=0.026) and had lower systolic and diastolic
      blood pressures (p<0.05). There was a significant graded relationship between the
      increase in mortality rate and tertile of heart rate (p<0.01). With multivariable
      analysis, age (p=0.037), heart rate (p<0.0001), diastolic blood pressure
      (p<0.001), prior ischemic heart disease (p=0.02) and creatinine (p=0.019) emerged
      as independent predictors of in-hospital mortality. After adjusting for
      predictors of poor prognosis, patients in the highest heart rate tertile had
      worst outcomes when compared with those in the lowest heart rate group (p=0.007).
      CONCLUSIONS: Higher heart rate 24-36h after admission for acute non-arrhythmic HF
      is associated with increased risk of in-hospital mortality. Early targeting of
      elevated heart rate might represent a complementary therapeutic challenge.

PMID- 25596463
TI  - Quantitative comparison of 21 protocols for labeling hippocampal subfields and
      parahippocampal subregions in in vivo MRI: towards a harmonized segmentation
      protocol.
AB  - OBJECTIVE: An increasing number of human in vivo magnetic resonance imaging (MRI)
      studies have focused on examining the structure and function of the subfields of
      the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum)
      and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and
      parahippocampal cortices). The ability to interpret the results of such studies
      and to relate them to each other would be improved if a common standard existed
      for labeling hippocampal subfields and parahippocampal subregions. Currently,
      research groups label different subsets of structures and use different rules,
      landmarks, and cues to define their anatomical extents. This paper characterizes,
      both qualitatively and quantitatively, the variability in the existing manual
      segmentation protocols for labeling hippocampal and parahippocampal substructures
      in MRI, with the goal of guiding subsequent work on developing a harmonized
      substructure segmentation protocol. METHOD: MRI scans of a single healthy adult
      human subject were acquired both at 3 T and 7 T. Representatives from 21 research
      groups applied their respective manual segmentation protocols to the MRI
      modalities of their choice. The resulting set of 21 segmentations was analyzed in
      a common anatomical space to quantify similarity and identify areas of agreement.
      RESULTS: The differences between the 21 protocols include the region within which
      segmentation is performed, the set of anatomical labels used, and the extents of
      specific anatomical labels. The greatest overall disagreement among the protocols
      is at the CA1/subiculum boundary, and disagreement across all structures is
      greatest in the anterior portion of the hippocampal formation relative to the
      body and tail. CONCLUSIONS: The combined examination of the 21 protocols in the
      same dataset suggests possible strategies towards developing a harmonized
      subfield segmentation protocol and facilitates comparison between published
      studies.

PMID- 25596470
TI  - In vivo evaluation of fibrous cap thickness by optical coherence tomography for
      positive remodeling and low-attenuation plaques assessed by computed tomography
      angiography.
AB  - BACKGROUND: Coronary plaques with positive remodeling (PR) and low-attenuation
      plaques (LAP) by computed tomography angiography (CTA) might be associated with
      plaque vulnerability. The purpose of this study was to assess the relation
      between coronary plaques with PR and LAP by CTA and fibrous cap thickness
      measured by optical coherence tomography (OCT). METHODS: We used CTA and OCT to
      assess 102 coronary plaques in patients with coronary artery disease (unstable
      angina pectoris, n=24; stable angina pectoris, n=78). Plaque characteristics were
      divided into three groups: 2-feature-positive plaques (PR and LAP; n=32), 1
      feature-positive plaques (PR or LAP; n=20), and 2-feature-negative plaques
      (neither PR nor LAP; n=50). PR was defined as remodeling index (RI) of >1.05 and
      LAP was defined as CT density value <50HU. RESULTS: There were significant
      differences between the three plaque groups with respect to fibrous cap thickness
      measured by OCT: 76+/-24MUm in 2-feature-positive plaques, 154+/-51MUm in 1
      feature-positive plaques, and 192+/-49MUm in 2-feature-negative plaques
      (P<0.001). The RI (1.21+/-0.06, 1.14+/-0.05, P=0.011) and the presence of thin
      cap fibroatheroma (TCFA) (<70-MUm thickness) (75%, 15%, P=0.001) were
      significantly higher in UAP than in SAP patients with 2-feature-positive plaques,
      whereas fibrous cap thickness (68.9+/-24.1, 92.1+/-21.9MUm, P<0.001) was lower in
      the UAP patients. In UAP patients, the presence of ring-like enhancement showed
      higher accuracy of 88% for detection of TCFA. CONCLUSIONS: Coronary PR and LAP by
      CTA were associated with the degree of fibrous cap thickness measured by OCT. CTA
      can non-invasively provide promising information on plaque vulnerability by
      identifying coronary plaque with PR and LAP, especially ring-like enhancement.

PMID- 25596473
TI  - Immunomodulatory characteristics of mesenchymal stem cells and their role in the
      treatment of multiple sclerosis.
AB  - Multiple Sclerosis (MS) is a chronic inflammatory neurodegenerative disease of
      central nervous system (CNS). Although the main cause of MS is not clear, studies
      suggest that MS is an autoimmune disease which attacks myelin sheath of neurons.
      There are different therapeutic regimens for MS patients including interferon
      (IFN)-beta, glatiramer acetate (GA), and natalizumab. However, such therapies are
      not quite effective and are associated with some side effects. So which, there is
      no complete therapeutic method for MS patients. Regarding the potent
      immunomodulatory effects of mesenchymal stem cells (MSCs) and their ameliorative
      effects in experimental autoimmune encephalopathy (EAE), it seems that MSCs may
      be a new therapeutic method in MS therapy. MSC transplantation is an approach to
      regulate the immune system in the region of CNS lesions. In this review, we have
      tried to discuss about the immunomodulatory properties of MSCs and their
      therapeutic mechanisms in MS patients. 

PMID- 25596474
TI  - Complexed soluble IL-7 receptor alpha and IL-7 increase IL-7-mediated
      proliferation and viability of CD8+ T-cells in vitro.
AB  - Many soluble cytokine receptors inhibit cytokine bioactivity, while others
      prolong ligand activity. The biological role of an endogenous soluble form of IL
      7Ralpha, or its therapeutic effects on CD8(+) T-cells are unknown. We demonstrate
      that recombinant IL-7Ralpha-Fc, when pre-incubated with IL-7, enhances IL-7
      induced CD8(+) T-cell proliferation and viability of human or murine CD8(+) T
      cells. Receptor blocking experiments confirmed IL-7-specific activity. These data
      demonstrate that exogenous soluble IL-7Ralpha significantly enhances CD8(+) T
      cell responses to IL-7 in vitro and paves the way for future research to
      determine its therapeutic potential to restore impaired CD8(+) T-cell function in
      disease. 

PMID- 25596472
TI  - Dexamethasone for the prevention of postoperative atrial fibrillation.
AB  - BACKGROUND: Postoperative atrial fibrillation (AF) is a common complication after
      cardiac surgery. Inflammation is believed to play a pivotal role in the etiology
      of postoperative AF. There is a suggestion from small studies that perioperative
      treatment with corticosteroids may reduce postoperative AF. The DExamethasone for
      Cardiac Surgery (DECS) study was a large randomized trial showing no protective
      effect of dexamethasone on major adverse events. The aim of this study was to
      investigate the effect of dexamethasone treatment on the occurrence of AF after
      cardiac surgery. METHODS: The DECS study compared intra-operative dexamethasone
      (1mg/kg) or placebo treatment in 4494 adult patients undergoing cardiac surgery.
      AF was defined by the occurrence of any reported AF within 30days after surgery.
      We also performed an in-depth analysis of a subset of 1565 patients on new-onset
      AF. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated.
      RESULTS: The incidence of any AF in the main study of 4494 patients was 33.1% in
      the dexamethasone and 35.2% in the placebo group (RR 0.94, 95% CI: 0.87-1.02,
      p=0.14). In the substudy of 1565 patients, the incidence of new-onset AF was
      33.0% vs. 35.5% (RR 0.93, 95% CI: 0.81-1.07, p=0.31), respectively. There was no
      protective effect of dexamethasone across clinically important patient subgroups.
      CONCLUSION: Intraoperative administration of dexamethasone had no protective
      effect on the occurrence of any or new-onset atrial fibrillation after cardiac
      surgery. Therefore, the use of dexamethasone for the reduction of postoperative
      AF should not be recommended.

PMID- 25596475
TI  - Manipulating IL-10 signalling blockade for better immunotherapy.
AB  - Interleukin 10 is a cytokine with the ability to reduce or terminate
      inflammation. Chronic viral infection, such as infection of chronic hepatitis B,
      hepatitis C and HIV, has increased levels of interleukin 10 in peripheral blood.
      Serum IL-10 levels are also high in certain cancers. Blocking IL-10 signalling at
      the time of immunisation clears chronic viral infection and prevents tumour
      growth in animal models. We review recent advances in this area, with the
      emphasis on potential use of this novel strategy to treat chronic viral infection
      and cancer in human. 

PMID- 25596476
TI  - Impact of a randomized trial on maintenance tocolysis on length of hospital
      admission of women with threatened preterm labor in The Netherlands.
AB  - INTRODUCTION: The APOSTEL-II trial was a multicenter randomized placebo
      controlled trial, assessing the effectiveness of maintenance tocolysis with
      nifedipine. The trial showed maintenance tocolysis not to have an effect on
      perinatal outcome. Objective of the current study is to evaluate the effect of a
      negative trial on the length of hospital admission of women with threatened
      preterm labor. MATERIALS AND METHODS: We evaluated length of hospital admission
      of all patients admitted with threatened preterm labor with a gestational age <32
      weeks in 8 perinatal centers that participated in the APOSTEL-II trial. We
      studied only the first admission with threatened preterm labor, readmissions were
      excluded. We distinguished between the period before, the period during and the
      period after the trial. In a subgroup analysis, we differentiated for the group
      of women who delivered and for the group of women who did not deliver during the
      initial admission. RESULTS: The mean length of hospital admission was 9.3 days
      before the start of the trial, 8.4 days during the recruitment period and 8.1
      days after the trial was completed. The difference in mean length of hospital
      admission before and during the recruitment period was significantly different
      (p<001). COMMENTS: The length of hospital admission of women with threatened
      preterm labor is found to be reduced during the recruitment period of the APOSTEL
      II trial. This shows that the conduct of a randomized controlled trial itself has
      the potential to change daily practice.

PMID- 25596477
TI  - Synthesis and L-type calcium channel blocking activity of new chiral
      oxadiazolothiazinones.
AB  - Oxadiazolo[3,4-c][1,4]thiazin-3-ones are cardiovascular agents that block L-type
      calcium channels. Previous data of cardiac and vasorelaxant activity on guinea
      pig for several derivatives indicated the two positions ortho to the thiazine's
      sulphur as crucial for modulating the activity; but these positions are likely
      susceptible to metabolic biotransformations, as indicated by in silico
      predictions. We designed new derivatives, and obtained three negative inotropic
      agents with EC50 in the low nanomolar range, more potent than all the precursors
      published so far. In particular, benzocondensation at the thiazine ring led to 3a
      (EC50 = 0.013 MUM) and 3b (EC50 = 0.006 MUM). Besides negative inotropy, we also
      observed relaxant activity on nonvascular muscle in the micromolar range. We
      resolved the new derivatives by chiral chromatography, and determined their
      absolute configuration by comparing experimental and calculated chiroptical
      properties (VCD, ECD and ORD): they hold the same absolute configuration-optical
      rotation relationship, (S)-(+)/(R)-(-). Both cardiac and nonvascular activity are
      majorly or mostly retained in the R-form for all the compounds, but for the
      nonvascular activity we observed a strong stereoselectivity for 3a, with the R
      form in the nanomolar range (IC50 = 0.020 MUM) and 259-fold more potent than the
      S-one. 

PMID- 25596478
TI  - Design, synthesis and biological profile of new inhibitors of multidrug
      resistance associated proteins carrying a polycyclic scaffold.
AB  - Following the identification of a novel polycyclic scaffold, leading to the
      previously reported potent P-gp modulator 1, a small series of easily affordable
      derivatives bearing a properly selected nitrogen-containing but-2-ynyl side chain
      was now synthesized and tested to evaluate the MDR reverting activity on two
      different experimental models. All compounds proved not to be cytotoxic when
      tested alone and more potent chemosensitizers than the reference verapamil. Some
      of them showed remarkable effects in combination with doxorubicin, being able to
      induce apoptotic cell death due to their reverting activity. In particular, 2a
      and 2c could be regarded as non-toxic new potential chemosensitizers, being able
      to interfere with different ABC proteins. Moreover, the intrinsic cytotoxicity of
      compound 1 could broaden its employment as MDR modulator. These results also seem
      to confirm the polycyclic core of these compounds as a potential new
      pharmacophoric carrier in medicinal chemistry. 

PMID- 25596479
TI  - Design, synthesis and biological evaluation of piperic acid triazolyl derivatives
      as potent anti-inflammatory agents.
AB  - Nineteen novel piperine based triazoles have been synthesized using click
      chemistry approach and were tested for in vivo anti-inflammatory activity. The
      most active compounds were evaluated for in vitro TNF-alpha expression. Compounds
      3g and 3f were found to show significant in vivo inhibition of inflammation,
      80.40% and 76.71%, respectively after 5 h in comparison to piperine (54.72%) and
      the standard drug indomethacin (77.02%) without causing any damage to the
      stomach. Compounds 3g and 3f suppressed TNF-alpha level by 73.73% and 70.64%,
      respectively and protein expression of COX-2, NF-kappaB and TNF-alpha more than
      indomethacin. Moreover, the compound 3g was found to show significant analgesic
      activity of 54.09% which was comparable with the indomethacin (57.43%). 

PMID- 25596480
TI  - Switch regulation of interleukin-1 beta in downstream of inflammatory cytokines
      induced by two micro-sized silica particles on differentiated THP-1 macrophages.
AB  - To investigate the regulated role of IL-1beta in initiating and maintaining
      inflammation, PMA-differentiated THP-1 macrophages were exposed to two micro
      sized crystalline silica particles (Si3-5MUm and Si1MUm) from 3h to 24h,
      respectively. Cytotoxicity and inflammatory cytokines (IL-1beta, TNF-alpha and IL
      6) expressions measured showed that they were induced by both silica particles in
      positive dose-dependent manners. The levels of inflammatory cytokines induced by
      Si1MUm were higher than those induced by Si3-5MUm at low concentration. When
      pretreated with anti-human IL-1beta, not only the high levels of IL-1beta but
      also elevated TNF-alpha and IL-6 induced by both silica particles were remarkably
      blocked, especially Si1MUm particle. In addition, recombinant human IL-1beta
      protein could induce macrophages to strikingly augment TNF-alpha and IL-6
      expressions. Our data suggest that IL-1beta could play a critical role of
      switching regulation in the downstream inflammation induced by micro-sized silica
      particles. 

PMID- 25596481
TI  - Future of nano bisdemethoxy curcumin analog: guaranteeing safer intravenous
      delivery.
AB  - The present study deals with the toxicity assessment of NBDMCA in vitro using red
      cell model and in vivo using rat model. Hemolysis was used as toxicity index in
      red blood cells. Different concentrations of NBDMCA viz., 20, 40, 60, 80,
      100MUg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found
      to induce less than 3% hemolysis in intact erythrocytes which was far lesser than
      the accepted threshold of 5%. Hematological cum biochemical parameters along with
      histopathological analysis and hemolysis were used as toxicity indices in rats.
      Whole blood of the NBDMCA-treated rats and control rats were analyzed for
      hematological parameters: erythrocyte count, leukocyte count, leukocyte
      differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean
      corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All
      hematological parameters analyzed were within the normal values in both the
      groups. Plasma samples were analyzed for biochemical parameters including
      glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin
      (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated
      biochemistry analyzer. Invariably, all the biochemical parameters are
      significantly similar in both the groups. Gross examination of vital organs like
      lung, heart, kidney, spleen and brain reveals no detectable abnormalities in
      NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen
      and kidneys of the experimental animals were collected and fixed in 10% formalin,
      processed in vacuum infiltration tissue processor, embedded with paraffin wax and
      sectioned at approximately 5MUm thick, stained with hematoxylin and eosin. The
      sections were examined and imaged through light microscopy. NBDMCA did not
      produce any significant changes in the histoarchitecture of all the organs
      studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal
      pathology report. The histopathological data correlated with the biochemical
      results indicating normal hepatocellular and nephrotic function. Our
      investigation clearly revealed that NBDMCA is hemocompatible in vitro and also
      safe to vital organs in vivo. We conclude that NBDMCA is non-toxic and safe and
      can be promoted as an ideal therapeutic tool for human use. 

PMID- 25596482
TI  - Nano-structured and functionalized surfaces for cytocompatibility improvement and
      bactericidal action.
AB  - The field of material surface modification with the aim of biomaterial
      construction involves several approaches of treatments that allow the preparation
      of materials, which positively influence adhesion of cells and their
      proliferation and thus aid and improve tissue formation. Modified materials have
      a surface composition and morphology intended to interact with biological systems
      and cellular functions. Not only surface chemistry has an effect on material
      biological response, surface structures of different morphology can be
      constructed to guide a desirable biological outcome. Nano-patterned material
      surfaces have been tested with the aim of how surface geometry and physical
      properties on a micro- and nano-scale can affect cellular response and influence
      cell adhesion and proliferation. Biological functionality of solid state
      substrates was significantly improved by the irradiation of material with plasma
      discharge or laser treatment. Commonly used "artificial" polymers (e.g.
      polyethylene (PE), polystyrene (PS), polytetrafluoroethylene (PTFE), polyethylene
      terephthalate (PET), polyethylene naphthalate (PEN)) and biopolymers (e.g. Poly-l
      Lactic acid (PLLA), polymethylpentene (PMP)) were treated with aim of
      biocompatibility improvement. The treatment of polymer/biopolymer substrates
      leads to formation of ripple or wrinkle-like structures, supported also with heat
      treatment or other subsequent surface processing. Several types of chemically
      different substances (e.g. metal or carbon nano-particles, proteins) were grafted
      onto material surfaces or built into material structures by different processes.
      Surface physico-chemical properties (e.g. chemistry, charge, morphology,
      wettability, electrical conductivity, optical and mechanical properties) of
      treated surfaces were determined. The enhancement of adhesion and proliferation
      of cells on modified substrates was investigated in vitro. Bactericidal action of
      noble metal nano-particles (e.g. Au, Ag) on polymers was characterized. The
      influence of metal nano-particle grafting by using metal nano-particle suspension
      prepared by "green" methods was determined. Micro- and nano-patterned surfaces
      can be constructed as tissue scaffolds with specific functions regarding cell
      adhesion and proliferation or potential biosensor applications. 

PMID- 25596484
TI  - Dual routes to cortical orienting responses: novelty detection and uncertainty
      reduction.
AB  - Sokolov distinguished between reactive and proactive variants of the orienting
      response (OR). The Novelty P3 is considered as an electrophysiological signature
      of the reactive OR. Recent work suggests that the proactive OR is reflected in
      frontally distributed P3 activity elicited by uncertainty-reducing stimuli in
      task-switching paradigms. Here, we directly compare the electrophysiological
      signatures of reactive and proactive ORs. Participants completed a novelty
      oddball task and a task-switching procedure while the electroencephalogram was
      measured. Novel and uncertainty-reducing stimuli evoked prominent fronto
      centrally distributed Novelty P3 and Uncertainty P3 waves, respectively. We found
      a substantial negative correlation between Novelty P3 and Uncertainty P3 across
      participants, suggesting that reactive and proactive ORs converge on a common
      neural pathway, but also that distinguishable routes to orienting exist.
      Moreover, response accuracy was associated with reduced Novelty-P3 and enhanced
      Uncertainty-P3 amplitudes. The relation between Novelty P3 and Uncertainty P3
      might serve as an index of individual differences in distractibility and
      cognitive control. 

PMID- 25596485
TI  - Anterior stabilization for unstable traumatic thoracolumbar spine burst
      fractures.
AB  - BACKGROUND: Traumatic injuries to the thoracolumbar spine result in a high
      incidence of unstable fractures. The goal of the surgical management is to
      achieve an adequate decompression and stabilization. We have analyzed operative
      and postoperative features of anterior surgical approaches. METHODS: We
      retrospectively analyzed the medical records of 45 patients that presented with
      traumatic unstable thoracolumbar fractures who underwent anterior corpectomy with
      stabilization from January 1999 to January 2009. The neurological status of the
      patient was defined using the American Spinal Injury Association (ASIA)
      impairment scale. RESULTS: The average age of the patients was 37.6 years (range:
      13-70), with a male-to-female ratio of 1.5:1. Retroperitoneal approach was used
      in 64.4%, transthoracic in 13.3%, and transthoracic transdiaghragmatic in 22.2%.
      The average operation time, estimated blood loss (EBL), and length of stay after
      surgery was 412.3 min, 1098 ml and 9.1 days, respectively. A BMI>25 was
      associated with longer operative times (p<0.02) and higher EBL (p<0.006).
      Perioperative complications occurred in 37.7%, (7 major, 10 minor). The mean
      sagittal angulation improved from 15.5 degree preoperatively to 8.7 degree
      postoperatively (p<0.001). Postoperative neurological status remained intact in
      all patients having preoperative ASIA-E status (n=18), improved in 7 of 14
      patients with ASIA-D, and improved in 1 of 5 patients with ASIA-B preoperative
      neurological deficit. There were no cases of neurological deterioration
      postoperatively, and majority of the patient (84.4%) of the patients were
      discharged home. At latest follow-up (mean 27.2 months) there were no new cases
      of neurological deficits, and 9 patients had a further improvement of
      neurological status. CONCLUSIONS: Based on our findings, anterior surgical
      approach appears to be a safe and effective technique for managing traumatic
      thoracic and lumbar unstable burst fractures. This is also evident that anterior
      decompression and stabilization achieves a significant correction of kyphotic
      deformity with a lower risk of neurological deterioration and pseudoarthrosis.

PMID- 25596486
TI  - Could ventriculoperitoneal shunt and tracheotomy procedures be realized in the
      same surgical time?
AB  - BACKGROUND: Both tracheotomy and ventriculoperitoneal shunting procedures may be
      required for the same critically ill patient. However, the risk of surgical site
      infection (SSI) may be increased if both procedures are performed simultaneously.
      METHOD: We performed a retrospective analysis of 41 consecutive patients who
      underwent both procedures simultaneously in our institution between March 2000
      and January 2008. RESULTS: Analysis revealed no difference in SSI rate between
      patients undergoing both procedures simultaneously and in staged procedures.
      CONCLUSIONS: VP shunting and tracheotomy procedures could be performed
      simultaneously without increasing the risk of surgical site infection. Such
      strategy may shorten the length of stay in critical care units.

PMID- 25596483
TI  - Age-related differences in early novelty processing: using PCA to parse the
      overlapping anterior P2 and N2 components.
AB  - Previous work demonstrated age-associated increases in the anterior P2 and age
      related decreases in the anterior N2 in response to novel stimuli. Principal
      component analysis (PCA) was used to determine if the inverse relationship
      between these components was due to their temporal and spatial overlap. PCA
      revealed an early anterior P2, sensitive to task relevance, and a late anterior
      P2, responsive to novelty, both exhibiting age-related amplitude increases. A PCA
      factor representing the anterior N2, sensitive to novelty, exhibited age-related
      amplitude decreases. The late P2 and N2 to novels inversely correlated. Larger
      late P2 amplitude to novels was associated with better behavioral performance.
      Age-related differences in the anterior P2 and N2 to novel stimuli likely
      represent age-associated changes in independent cognitive operations. Enhanced
      anterior P2 activity (indexing augmentation in motivational salience) may be a
      compensatory mechanism for diminished anterior N2 activity (indexing reduced
      ability of older adults to process ambiguous representations). 

PMID- 25596487
TI  - A comparison of montreal cognitive assessment between patients with visual
      hallucinations and without visual hallucinations in Parkinson's disease.
AB  - BACKGROUND: Visual hallucination (VH) is closely associated with cognitive
      impairment in Parkinson's disease (PD). The aim of this study is to analyze the
      domain of cognitive impairment related to the VH by analyzing cognition in PD.
      METHOD: Twenty-six of 58 patients had VH (PD-VH), whereas 32 patients had no
      hallucinations (PD-NH); patients assigned to the PD-VH on the basis of having at
      least one VH per week for one month before participation in the study. All of the
      patients were administered the Montreal Cognitive Assessment-Korean test (MoCA
      K). We analyzed the differences in cognition between PD-VH and PD-NH. RESULTS:
      The Hoehn-Yahr (HY) stage and the Beck Depression Inventory version I (BDI)
      scores in PD-VH were significantly different from those in PD-NH. After adjusting
      for the HY stage and BDI, the language domain of the MoCA-K cognitive domains
      presents a significant difference between PD-VH and PD-NH. CONCLUSION: Sentence
      processing and naming as the composition of the language domain in the MoCA-K
      have been associated in common with posterior cortical dysfunction. Although our
      result shows that the language domain of MoCA-K is sensitive to cognitive deficit
      in PD-VH patients, it needs further neuroimaging analysis for certifying the
      relationship between language impairment and posterior cortical deficit as the
      pathophysiology of PD-VH.

PMID- 25596488
TI  - ?Copper (II) ions modulate Angiogenin activity in human endothelial cells.
AB  - Angiogenin (ANG), a member of the secreted ribonuclease family, is a potent
      angiogenesis stimulator that interacts with endothelial cells inducing a wide
      range of responses. Metal ions dyshomeostasis play a fundamental role in the
      onset of neurodegenerative diseases, in particular copper that is also involved
      in angiogenesis processes. It is known that vascular pathologies are present in
      neurodegenerative diseases and Angiogenin is down-regulated in Alzheimer and
      Parkinson diseases, as well as it has been found as one of the mutated genes in
      amyotrophic lateral sclerosis (ALS). Copper (II) induces an increase of
      Angiogenin binding to endothelial cells but, so far, the relationship between
      copper-ANG and angiogenesis induction remain unclear. Herein, the effects of
      copper (II) ions on Angiogenin activity and expression were evaluated. The
      binding of copper was demonstrated to affect the intracellular localization of
      the protein decreasing its nuclear translocation. Moreover, the ANG-copper (II)
      system negatively affects the protein-induced angiogenesis, as well as
      endothelial cells migration. Surprisingly, copper also reveals the ability to
      modulate the Angiogenin transcription. These results highlight the tight
      relationship between copper and Angiogenin, pointing out the biological relevance
      of ANG-copper system in the regulation of endothelial cell function, and
      revealing a possible new mechanism at the basis of vascular pathologies. 

PMID- 25596489
TI  - Mitochondrial large-conductance potassium channel from Dictyostelium discoideum.
AB  - In the present study, we describe the existence of a large-conductance calcium
      activated potassium (BKCa) channel in the mitochondria of Dictyostelium
      discoideum. A single-channel current was recorded in a reconstituted system,
      using planar lipid bilayers. The large-conductance potassium channel activity of
      258+/-12 pS was recorded in a 50/150 mM KCl gradient solution. The probability of
      channel opening (the channel activity) was increased by calcium ions and NS1619
      (potassium channel opener) and reduced by iberiotoxin (BKCa channel inhibitor).
      The substances known to modulate BKCa channel activity influenced the
      bioenergetics of D. discoideum mitochondria. In isolated mitochondria, NS1619 and
      NS11021 stimulated non-phosphorylating respiration and depolarized membrane
      potential, indicating the channel activation. These effects were blocked by
      iberiotoxin and paxilline. Moreover, the activation of the channel resulted in
      attenuation of superoxide formation, but its inhibition had the opposite effect.
      Immunological analysis with antibodies raised against mammalian BKCa channel
      subunits detected a pore-forming alpha subunit and auxiliary beta subunits of the
      channel in D. discoideum mitochondria. In conclusion, we show for the first time
      that mitochondria of D. discoideum, a unicellular ameboid protozoon that
      facultatively forms multicellular structures, contain a large-conductance calcium
      activated potassium channel with electrophysiological, biochemical and molecular
      properties similar to those of the channels previously described in mammalian and
      plant mitochondria.

PMID- 25596490
TI  - The serotonin transporter (5-HTTLPR) but not serotonin receptor (5-HT2C Cys23Ser)
      variant is associated with bipolar I disorder in Kurdish population from Western
      Iran.
AB  - The role of 5-HTTLPR and 5-HT2C Cys23Ser polymorphisms in the psychopathology of
      mood disorders and suicide behavior is controversial. The aim of present study
      was to investigate the association between 5-HTTLPR and 5-HT2C Cys23Ser variants
      and susceptibility to bipolar I disorder (BID). The 5-HT2C genotypes were studied
      in 152 patients with BID and 173 gender- and age-matched healthy individuals with
      Kurds ethnic background from Western Iran using PCR and PCR-RFLP methods. In
      recessive model (SS vs. LL+LS) the SS genotype was associated with 1.79-fold
      increased risk of BID (p=0.018). Also, the presence of S allele increased the
      risk of adult-onset BID by 1.76-fold (p=0.027). No association was detected
      between 5-HTTLPR genotypes and alleles with suicide attempt. The frequency of 5
      HT2C Ser allele in patients and controls were 12.3 and 12.5%, respectively.
      Mutant allele of HT2C Ser had higher frequency in female (14.7%) than male
      (10.5%, p=0.27) patients. The frequency of HT2C Ser allele in patients with a
      family history of BID tended to be higher (15.7%) than those without a family
      history of the disease (11.8%). The frequency of HT2C Ser allele in suicide
      attempter women was higher (16.7%) than those without a suicide attempt (14.3%).
      Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and
      adult-onset BID in Kurds population. However, we found the lack of an association
      between 5-HT2C Cys/Ser variants and the risk of BID. 

PMID- 25596491
TI  - A newly designed molecule J2326 for Alzheimer's disease disaggregates amyloid
      fibrils and induces neurite outgrowth.
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by deposition
      of beta-amyloid (Abeta) fibrils accompanied with progressive neurite loss. None
      of the clinically approved anti-Alzheimer's agents target both pathological
      processes. We hypothesized that conjugation of a metal chelator to destabilize
      Abeta fibrils (fAbetas) and a long-chain fatty alcohol to induce neurite
      outgrowth may generate a novel molecular scaffold that targets both pathologies.
      The hydroxyalkylquinoline J2326 was designed and synthesized by joining an 11
      carbon alcohol to 5-chloro-8-methoxyquinoline at the 2-position and its anti
      neurodegenerative potentials in vitro and in vivo were characterized. It
      attenuated fAbeta formation and disaggregated the existing fAbeta zinc
      dependently as well as zinc-independently. It also triggered extracellular signal
      regulated kinase-dependent neurite outgrowth and increased synaptic activity in
      neuronal cells. In fAbeta-driven neurodegeneration in vitro, J2326 reversed
      neurite collapse and neurotoxicity. These roles of J2326 were also demonstrated
      in vivo and were pivotal to the observed improvement in memory of mice with
      hippocampal fAbeta lesions. These results show that the effectiveness of J2326 on
      fAbeta-driven neurodegeneration is ascribed to its novel scaffold. This might
      give clues to evolving attractive therapy for future clinical trials. 

PMID- 25596493
TI  - Performance of mixed-species biocathode microbial fuel cells using saline mustard
      tuber wastewater as self-buffered catholyte.
AB  - Mixed-species biocathode microbial fuel cells (MFCs) were constructed. Mustard
      tuber wastewater (MTWW) was used as catholyte. Simultaneous organic matters and
      nitrogen removal at the cathode was observed, and majority of contaminants
      reduced were accomplished within acclimating period (AP). Concerning nitrogen
      removal, aerobic and anaerobic microenvironment could be formed within the
      cathodic biofilms, and both heterotrophic denitrification and bioelectrochemical
      denitrification were involved. Also, it was demonstrated that organic matters and
      ammonium could have detrimental effects on voltage output, but it could retrieve
      finally. Similar maximum power densities were obtained during stage1 (1.20Wm(
      3)), stage2 (1.24Wm(-3)) and stage3 (1.32Wm(-3)). However, overpotential for
      oxygen reduction was investigated due to lower bacteria activity at cathode,
      which could major limitation for energy recovery. Considering similar performance
      of MFCs during different stages, it could be concluded that MTWW was adequately
      self-buffered when used as catholyte at mixed-species biocathodes. 

PMID- 25596492
TI  - Cocaine-seeking is associated with PKC-dependent reduction of excitatory
      signaling in accumbens shell D2 dopamine receptor-expressing neurons.
AB  - Stimulation of D1-like dopamine receptors (D1DRs) or D2-like dopamine receptors
      (D2DRs) in the nucleus accumbens (NAc) shell reinstates cocaine seeking in rats,
      an animal model of relapse. D2DRs and D1DRs activate protein kinase C (PKC) and
      recent studies indicate that activation of PKC in the NAc plays an important role
      in the reinstatement of drug seeking induced by a systemic cocaine priming
      injection. In the present study, pharmacological inhibition of PKC in the NAc
      shell attenuated cocaine seeking induced by intra-accumbens shell microinjection
      of a D2DR agonist, but not a D1DR agonist. D1DRs and D2DRs are primarily
      expressed on different accumbens medium spiny (MSN) neurons. Neuronal signaling
      and activity were assessed in these two populations of NAc neurons with
      transgenic mice expressing fluorescent labels under the control of D1DR and D2DR
      promoters. Following the extinction of cocaine self-administration, bath
      application of a PKC inhibitor produced similar effects on single evoked
      excitatory and inhibitory post-synaptic currents in D1DR- and D2DR-positive MSNs
      in the NAc shell. However, inhibition of PKC preferentially improved the ability
      of excitatory, but not inhibitory, synapses to sustain responding to brief train
      of stimuli specifically in D2DR-positive MSNs. This effect did not appear to
      involve modulation of presynaptic release mechanisms. Taken together, these
      findings indicate that the reinstatement of cocaine seeking is at least partially
      due to D2DR-dependent increases in PKC signaling in the NAc shell, which reduce
      excitatory synaptic efficacy in D2DR-expressing MSNs. 

PMID- 25596495
TI  - Piscine orthoreovirus (PRV) o3 protein binds dsRNA.
AB  - Piscine orthoreovirus (PRV) has a double-stranded, segmented RNA genome and
      belongs to the family Reoviridae. PRV is associated with heart and skeletal
      muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar L.) and cause
      intraerythrocytic inclusions. The virus is widespread in both wild and farmed
      salmonid fish in Europe, North- and South America. In mammalian orthoreovirus
      (MRV), the outer capsid protein o3 has dsRNA binding properties, which serve to
      inhibit the early innate immune response of the host. Important structural motifs
      and key amino acid residues are conserved between MRV o3 and the homologous PRV
      protein, and we hypothesized that PRV o3 binds dsRNA. Gene regions and amino acid
      residues predicted to be important for dsRNA binding were determined through
      bioinformatic analysis and investigated functionally following site-directed
      mutagenesis and the generation of truncated o3 variants. Our results provide
      evidence that the PRV protein o3 binds dsRNA in a sequence independent manner,
      thus sharing this function with MRV o3. Although no specific domain solely
      responsible for dsRNA binding was determined, the results point to residues
      within a predominantly basic region to be important for this functional property.
      We conclude that multiple sites are involved in the dsRNA binding activity of PRV
      o3. 

PMID- 25596494
TI  - Stability of P50 auditory sensory gating during sleep from infancy to 4 years of
      age.
AB  - The stability of cerebral inhibition was assessed across early childhood using a
      paired-click auditory sensory gating paradigm. The P50 ERP was measured during
      REM (or its infant analogue, active sleep) and NREM sleep in 14 children at
      approximately 3 months of age and again at approximately 4 years of age. Evoked
      response amplitudes, latencies, and the S2/S1 ratio of the amplitudes of the
      evoked responses were compared between the two visits. Significant reliability
      was found for the S2/S1 ratio (r = .73, p = .003) during REM but not non REM
      sleep (r = -.05, p = .88). A significant stimulus number by sleep stage
      interaction (F(1,12) = 17.1, p = .001) demonstrated that the response to the
      second stimulus decreased during REM but not NREM sleep. These findings suggest
      that this measure is stable during REM sleep across early childhood, is not
      affected by age, and is sleep-state dependent. P50 sensory gating is a biomarker
      which, if used properly, may provide a mechanism to further explore changes in
      the developing brain or may help with early screening for psychiatric illness
      vulnerability.

PMID- 25596496
TI  - Lack of antiviral antibody response in koalas infected with koala retroviruses
      (KoRV).
AB  - Many wild koalas are infected with the koala retrovirus, KoRV, some of which
      suffer from lymphoma and chlamydial disease. Three subgroups, KoRV-A, KoRV-B and
      KoRV-J, have so far been described. It is well known that other closely related
      gammaretroviruses can induce tumours and severe immunodeficiencies in their
      respective hosts and a possible role for KoRV infection in lymphoma and
      chlamydial disease in koalas has been suggested. In many wild koalas, KoRV-A has
      become endogenised, i.e., it is integrated in the germ-line and is passed on with
      normal cellular genes. In this study, sera from koalas in European zoos and from
      wild animals in Australia were screened for antibodies against KoRV-A. These
      naturally infected animals all carry endogenous KoRV-A and two zoo animals are
      also infected with KoRV-B. The antibody response is generally an important
      diagnostic tool for detecting retrovirus infections. However, when Western blot
      analyses were performed using purified virus or recombinant proteins
      corresponding to KoRV-A, none of the koalas tested positive for specific
      antibodies, suggesting a state of tolerance. These results have implications for
      koala vaccination, as they suggest that therapeutic immunisation of animals
      carrying and expressing endogenous KoRV-A will not be successful. However, it
      remains unclear whether these animals can be immunised against KoRV-B and
      immunisation of uninfected koalas could still be worthwhile. 

PMID- 25596497
TI  - Intermediate filament structure: the bottom-up approach.
AB  - Intermediate filaments (IFs) result from a key cytoskeletal protein class in
      metazoan cells, but currently there is no consensus as to their three-dimensional
      architecture. IF proteins form elongated dimers based on the coiled-coil
      structure within their central 'rod' domain. Here we focus on the atomic
      structure of this elementary dimer, elucidated using X-ray crystallography on
      multiple fragments and electron paramagnetic resonance experiments on spin
      labelled vimentin samples. In line with conserved sequence features, the rod of
      all IF proteins is composed of three coiled-coil segments containing heptad and
      hendecad repeats and interconnected by linkers. In addition, the next assembly
      intermediate beyond the dimer, the tetramer, could be modelled. The impact of
      these structural results towards understanding the assembly mechanism is
      discussed. 

PMID- 25596498
TI  - Analysis of amino acid neurotransmitters from rat and mouse spinal cords by
      liquid chromatography with fluorescence detection.
AB  - A RP-LC-FL detection method has been developed to identify and quantitate four
      amino acid neurotransmitters including glutamic acid, glycine, taurine and gamma
      aminobutyric acid in rat and mouse spinal cord tissue. 3-(4-carboxybenzoyl)-2
      quinolinecarboxaldehyde (CBQCA) was employed for the derivatization of these
      neurotransmitters prior to RP-LC-FL analysis. Different parameters which
      influenced separation and derivatization were optimized. Under optimum
      conditions, linearity was achieved within the concentration ranges of 0.50-50.00
      MUM for all analytes with correlation coefficients from 0.9912 to 0.9997. The
      LODs ranged from 0.03 MUM to 0.06 MUM. The proposed method has been successfully
      applied to the determination of amino acid neurotransmitters in biological
      samples such as rat and mouse spinal cord with satisfactory recoveries.

PMID- 25596499
TI  - Thioredoxin rod-derived cone viability factor protects against photooxidative
      retinal damage.
AB  - Rod-derived cone viability factor (RdCVF) is a trophic factor of the thioredoxins
      family that promotes the survival of cone photoreceptors. It is encoded by the
      nucleoredoxin-like gene 1 Nxnl1 which also encodes by alternative splicing a long
      form of RdCVF (RdCVFL), a thioredoxin enzyme that interacts with TAU. The known
      role of thioredoxins in the defense mechanism against oxidative damage led us to
      examine the retinal phenotype of the Nxnl1(-/-) mice exposed to photooxidative
      stress. Here we found that, in contrast to wild-type mice, the rod photoreceptors
      of Nxnl1(-/-) mice are more sensitive to light after exposure to 1700 or 2500 lx.
      The delivery of RdCVF by AAV to mice deficient of Nxnl1(-/-) protects rod
      photoreceptors from light damage. Interestingly, the RdCVF2L protein, encoded by
      the paralog gene Nxnl2, is able to reduce TAU phosphorylation, as does RdCVFL,
      but does not protect the rod from light damage. Our result shows that the Nxnl1
      gene, through the thioredoxin RdCVFL, is part of an endogenous defense mechanism
      against photooxidative stress that is likely of great importance for human
      vision.

PMID- 25596500
TI  - Eating tasty food to cope. Longitudinal association with BMI.
AB  - The goals of this study were to determine if a change in certain motives to eat
      highly palatable food, as measured by the Palatable Eating Motives Scale (PEMS),
      could predict a change in body mass index (BMI) over time, to assess the temporal
      stability of these motive scores, and to test the reliability of previously
      reported associations between eating tasty foods to cope and BMI. BMI,
      demographics, and scores on the PEMS and the Binge Eating Scale were obtained
      from 192 college students. Test-retest analysis was performed on the PEMS motives
      in groups varying in three gap times between tests. Regression analyses
      determined what PEMS motives predicted a change in BMI over two years. The
      results replicated previous findings that eating palatable food for Coping
      motives (e.g., to forget about problems, reduce negative feelings) is associated
      with BMI. Test-retest correlations revealed that motive scores, while somewhat
      stable, can change over time. Importantly, among overweight participants, a
      change in Coping scores predicted a change in BMI over 2 years, such that a 1
      point change in Coping predicted a 1.76 change in BMI (equivalent to a 10.5 lb.
      change in body weight) independent of age, sex, ethnicity, and initial binge
      eating status (Cohen's f(2) effect size = 1.44). The large range in change of
      Coping scores suggests it is possible to decrease frequency of eating to cope by
      more than 1 scale point to achieve weight losses greater than 10 lbs. in young
      overweight adults, a group already at risk for rapid weight gain. Hence,
      treatments aimed specifically at reducing palatable food intake for coping
      reasons vs. for social, reward, or conformity reasons, should help achieve a
      healthier body weight and prevent obesity if this motive-type is identified prior
      to significant weight gain. 

PMID- 25596501
TI  - Executive functioning, emotion regulation, eating self-regulation, and weight
      status in low-income preschool children: how do they relate?
AB  - The purpose of the present study was to examine relationships between child
      eating self-regulation, child non-eating self-regulation, and child BMIz in a low
      income sample of Hispanic families with preschoolers. The eating in the absence
      of hunger task as well as parent-report of child satiety responsiveness and food
      responsiveness were used to assess child eating self-regulation. Two laboratory
      tasks assessing executive functioning, a parent questionnaire assessing child
      effortful control (a temperament dimension related to executive functioning), and
      the delay of gratification and gift delay tasks assessing child emotion
      regulation were used to assess child non-eating self-regulation. Bivariate
      correlations were run among all variables in the study. Hierarchical linear
      regression analyses assessed: (1) child eating self-regulation associations with
      the demographic, executive functioning, effortful control, and emotion regulation
      measures; and (2) child BMI z-score associations with executive functioning,
      effortful control, emotion regulation measures, and eating self-regulation
      measures. Within child eating self-regulation, only the two parent-report
      measures were related. Low to moderate positive correlations were found between
      measures of executive functioning, effortful control, and emotion regulation.
      Only three relationships were found between child eating self-regulation and
      other forms of child self-regulation: eating in the absence of hunger was
      positively associated with delay of gratification, and poor regulation on the
      gift delay task was associated positively with maternal reports of food
      responsiveness and negatively with parent-reports of satiety responsiveness.
      Regression analyses showed that child eating self-regulation was associated with
      child BMIz but other forms of child self-regulation were not. Implications for
      understanding the role of self-regulation in the development of child obesity are
      discussed. 

PMID- 25596502
TI  - The conundrum of underfeeding vs overfeeding neurocritically ill patients: is
      less better?

PMID- 25596504
TI  - MicroRNAs as biomarker of Parkinson disease? Small but mighty.

PMID- 25596503
TI  - Inflammation, negative nitrogen balance, and outcome after aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To analyze the impact of inflammation and negative nitrogen balance
      (NBAL) on nutritional status and outcomes after subarachnoid hemorrhage (SAH).
      METHODS: This was a prospective observational study of SAH patients admitted
      between May 2008 and June 2012. Measurements of C-reactive protein (CRP),
      transthyretin (TTR), resting energy expenditure (REE), and NBAL (g/day) were
      performed over 4 preset time periods during the first 14 postbleed days (PBD) in
      addition to daily caloric intake. Factors associated with REE and NBAL were
      analyzed with multivariable linear regression. Hospital-acquired infections (HAI)
      were tracked daily for time-to-event analyses. Poor outcome at 3 months was
      defined as a modified Rankin Scale score >= 4 and assessed by multivariable
      logistic regression. RESULTS: There were 229 patients with an average age of 55
      +/- 15 years. Higher REE was associated with younger age (p = 0.02), male sex (p
      < 0.001), higher Hunt Hess grade (p = 0.001), and higher modified Fisher score (p
      = 0.01). Negative NBAL was associated with lower caloric intake (p < 0.001),
      higher body mass index (p < 0.001), aneurysm clipping (p = 0.03), and higher
      CRP:TTR ratio (p = 0.03). HAIs developed in 53 (23%) patients on mean PBD 8 +/-
      3. Older age (p = 0.002), higher Hunt Hess (p < 0.001), lower caloric intake (p =
      0.001), and negative NBAL (p = 0.04) predicted time to first HAI. Poor outcome at
      3 months was associated with higher Hunt Hess grade (p < 0.001), older age (p <
      0.001), negative NBAL (p = 0.01), HAI (p = 0.03), higher CRP:TTR ratio (p =
      0.04), higher body mass index (p = 0.03), and delayed cerebral ischemia (p =
      0.04). CONCLUSIONS: Negative NBAL after SAH is influenced by inflammation and
      associated with an increased risk of HAI and poor outcome. Underfeeding and
      systemic inflammation are potential modifiable risk factors for negative NBAL and
      poor outcome after SAH.

PMID- 25596505
TI  - Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients
      with PD.
AB  - OBJECTIVE: The aims of the present study were to profile the expression of
      several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive
      patients with Parkinson disease (PD) vs unaffected controls and to interpret the
      miRNA expression data in a biological context. METHODS: We analyzed RNAs from
      peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and
      unaffected controls matched 1:1 by sex and age. We evaluated expression by
      reverse transcription-quantitative real-time PCR, and we analyzed data using a 2
      tailed paired t test. To detect miRNA targets, several miRNA resources were
      combined to generate an overall score for each candidate gene using weighted rank
      aggregation. RESULTS: Significant overexpression of miR-103a-3p (p < 0.0001), miR
      30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was
      observed, and promising candidate target genes for these were revealed by an
      integrated in silico analysis. CONCLUSIONS: We revealed 3 candidate biomarkers
      for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD
      albeit opposite to published data, while for miR-103a-3p, we demonstrated for the
      first time an overexpression in treated patients with PD. Expression studies in
      patients and/or in isolated peripheral blood mononuclear cells before and after L
      dopa administration are necessary to define the involvement of L-dopa treatment
      in the observed overexpression. Our in silico analysis to prioritize targets of
      deregulated miRNAs identified candidate target genes, including genes related to
      neurodegeneration and PD. Despite the preliminary character of our study, the
      results provide a rationale for further clarifying the role of the identified
      miRNAs in the pathogenesis of PD and for validating their diagnostic potential.

PMID- 25596506
TI  - GRIN2A: an aptly named gene for speech dysfunction.
AB  - OBJECTIVE: To delineate the specific speech deficits in individuals with epilepsy
      aphasia syndromes associated with mutations in the glutamate receptor subunit
      gene GRIN2A. METHODS: We analyzed the speech phenotype associated with GRIN2A
      mutations in 11 individuals, aged 16 to 64 years, from 3 families. Standardized
      clinical speech assessments and perceptual analyses of conversational samples
      were conducted. RESULTS: Individuals showed a characteristic phenotype of
      dysarthria and dyspraxia with lifelong impact on speech intelligibility in some.
      Speech was typified by imprecise articulation (11/11, 100%), impaired pitch
      (monopitch 10/11, 91%) and prosody (stress errors 7/11, 64%), and hypernasality
      (7/11, 64%). Oral motor impairments and poor performance on maximum vowel
      duration (8/11, 73%) and repetition of monosyllables (10/11, 91%) and
      trisyllables (7/11, 64%) supported conversational speech findings. The speech
      phenotype was present in one individual who did not have seizures. CONCLUSIONS:
      Distinctive features of dysarthria and dyspraxia are found in individuals with
      GRIN2A mutations, often in the setting of epilepsy-aphasia syndromes; dysarthria
      has not been previously recognized in these disorders. Of note, the speech
      phenotype may occur in the absence of a seizure disorder, reinforcing an
      important role for GRIN2A in motor speech function. Our findings highlight the
      need for precise clinical speech assessment and intervention in this group. By
      understanding the mechanisms involved in GRIN2A disorders, targeted therapy may
      be designed to improve chronic lifelong deficits in intelligibility.

PMID- 25596507
TI  - Engineering Escherichia coli for methanol conversion.
AB  - Methylotrophic bacteria utilize methanol and other reduced one-carbon compounds
      as their sole source of carbon and energy. For this purpose, these bacteria
      evolved a number of specialized enzymes and pathways. Here, we used a synthetic
      biology approach to select and introduce a set of "methylotrophy genes" into
      Escherichia coli based on in silico considerations and flux balance analysis to
      enable methanol dissimilation and assimilation. We determined that the most
      promising approach allowing the utilization of methanol was the implementation of
      NAD-dependent methanol dehydrogenase and the establishment of the ribulose
      monophosphate cycle by expressing the genes for hexulose-6-phosphate synthase
      (Hps) and 6-phospho-3-hexuloisomerase (Phi). To test for the best-performing
      enzymes in the heterologous host, a number of enzyme candidates from different
      donor organisms were selected and systematically analyzed for their in vitro and
      in vivo activities in E. coli. Among these, Mdh2, Hps and Phi originating from
      Bacillus methanolicus were found to be the most effective. Labeling experiments
      using (13)C methanol with E. coli producing these enzymes showed up to 40%
      incorporation of methanol into central metabolites. The presence of the
      endogenous glutathione-dependent formaldehyde oxidation pathway of E. coli did
      not adversely affect the methanol conversion rate. Taken together, the results of
      this study represent a major advancement towards establishing synthetic
      methylotrophs by gene transfer. 

PMID- 25596508
TI  - Integrated 13C-metabolic flux analysis of 14 parallel labeling experiments in
      Escherichia coli.
AB  - The use of parallel labeling experiments for (13)C metabolic flux analysis ((13)C
      MFA) has emerged in recent years as the new gold standard in fluxomics. The
      methodology has been termed COMPLETE-MFA, short for complementary parallel
      labeling experiments technique for metabolic flux analysis. In this contribution,
      we have tested the limits of COMPLETE-MFA by demonstrating integrated analysis of
      14 parallel labeling experiments with Escherichia coli. An effort on such a
      massive scale has never been attempted before. In addition to several widely used
      isotopic tracers such as [1,2-(13)C]glucose and mixtures of [1-(13)C]glucose and
      [U-(13)C]glucose, four novel tracers were applied in this study: [2,3
      (13)C]glucose, [4,5,6-(13)C]glucose, [2,3,4,5,6-(13)C]glucose and a mixture of [1
      (13)C]glucose and [4,5,6-(13)C]glucose. This allowed us for the first time to
      compare the performance of a large number of isotopic tracers. Overall, there was
      no single best tracer for the entire E. coli metabolic network model. Tracers
      that produced well-resolved fluxes in the upper part of metabolism (glycolysis
      and pentose phosphate pathways) showed poor performance for fluxes in the lower
      part of metabolism (TCA cycle and anaplerotic reactions), and vice versa. The
      best tracer for upper metabolism was 80% [1-(13)C]glucose+20% [U-(13)C]glucose,
      while [4,5,6-(13)C]glucose and [5-(13)C]glucose both produced optimal flux
      resolution in the lower part of metabolism. COMPLETE-MFA improved both flux
      precision and flux observability, i.e. more independent fluxes were resolved with
      smaller confidence intervals, especially exchange fluxes. Overall, this study
      demonstrates that COMPLETE-MFA is a powerful approach for improving flux
      measurements and that this methodology should be considered in future studies
      that require very high flux resolution. 

PMID- 25596509
TI  - A synthetic suicide riboswitch for the high-throughput screening of metabolite
      production in Saccharomyces cerevisiae.
AB  - Artificial devices such as the synthetic riboswitch have shown potential to
      introduce unnatural phenotypic perturbation because its synthetic traits are
      distinct from that of innate metabolism. In this study, a riboswitch, a small
      regulatory element found in RNAs, was employed to reprogram microorganisms to
      produce valuable metabolites. A self-cleaving ribozyme glmS, found in gram
      positive bacteria, cleaves its own transcript in response to the intracellular
      glucosamine 6-phosphate (GlcN6P) concentration. The glmS ribozyme was integrated
      into the 3'-untranslated region of FCY1, which encodes cytosine deaminase in
      Saccharomyces cerevisiae to construct a suicide riboswitch for evolutionary
      engineering. Growth of the strain harboring the suicide riboswitch was hampered
      by the addition of fluorocytosine, and was recovered as metabolite level
      increased. By using this riboswitch, we isolated a N-acetyl glucosamine (GlcNAc)
      producer strain by screening an efficient glutamine-fructose-6-phosphate
      transaminase (Gfa1p) and haloacid dehalogenase-like phosphatases (HAD
      phosphatases) originated from Escherichia coli. The suicide riboswitch was also
      applied to different metabolite by using artificial allosteric ribozyme. Since
      the mechanisms used in this work are universal in microorganisms, our synthetic
      suicide riboswitch can be applied to a wide range of organisms and can be
      exploited to the efficient and high-throughput screening of inconspicuous
      phenotypes. 

PMID- 25596511
TI  - Integrating screening, brief intervention and referral to treatment (SBIRT) into
      an abortion clinic: an exploratory study of acceptability.
AB  - Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an effective
      means of identifying problematic substance use. We evaluated the acceptability of
      SBIRT in an abortion clinic via an anonymous survey of 100 participants. Clients
      were comfortable being asked about their substance use, receiving counseling, and
      treatment referral (mean Likert 1.1, 1.5, and 1.6, respectively) and were only
      minimally embarrassed when asked about substance use (mean Likert 3.6). These
      findings suggest that integrating SBIRT into an abortion clinic may be feasible.
      However, future studies are needed to assess the efficacy of abortion clinic
      SBIRT in reducing risky substance use. 

PMID- 25596510
TI  - Metabolic transistor strategy for controlling electron transfer chain activity in
      Escherichia coli.
AB  - A novel strategy to finely control a large metabolic flux by using a "metabolic
      transistor" approach was established. In this approach a small change in the
      level or availability of an essential component for the process is controlled by
      adding a competitive reaction that affects a precursor or an intermediate in its
      biosynthetic pathway. The change of the basal level of the essential component,
      considered as a base current in a transistor, has a large effect on the flux
      through the major pathway. In this way, the fine-tuning of a large flux can be
      accomplished. The "metabolic transistor" strategy was applied to control electron
      transfer chain function by manipulation of the quinone synthesis pathway in
      Escherichia coli. The achievement of a theoretical yield of lactate production
      under aerobic conditions via this strategy upon manipulation of the biosynthetic
      pathway of the key participant, ubiquinone-8 (Q8), in an E. coli strain provides
      an in vivo, genetically tunable means to control the activity of the electron
      transfer chain and manipulate the production of reduced products while limiting
      consumption of oxygen to a defined amount. 

PMID- 25596512
TI  - A review of the endometrial histologic effects of progestins and progesterone
      receptor modulators in reproductive age women.
AB  - This review compares the histologic changes that occur in the endometrium
      following ovulation and progesterone secretion with contraceptive progestins and
      progesterone receptor modulators (PRMs) that may be used as contraceptive agents
      in women. The morphologic endometrial changes vary by the progestin type, dosage
      and duration; are often subtle and difficult to interpret; and may also vary
      depending on whether or not estrogen is used. The prolonged use of ethinyl
      estradiol and a progestin as a combined oral contraceptive results in common
      endometrial histologic findings that include glandular and stromal atrophy and
      spiral arteriole underdevelopment. Intrauterine systems releasing levonorgestrel
      have similar changes that are related to the proximity of the device to the
      endometrium, while progestin-only implants result in atrophy with marked vascular
      changes characterized by underdevelopment of spiral arterioles and dilated, thin
      walled vessels near the surface epithelium. Lower doses of levonorgestrel
      delivered by a vaginal ring allow ovulation, and the endometrial changes appear
      to reflect the impact of the endogenous hormones. PRMs have been investigated as
      potential female contraceptives. PRM-associated endometrial changes include an
      inactive endometrium with cystically dilated glands, lined by epithelium with
      increased apoptosis in a background of compact nondecidualized stroma. Histologic
      differences between PRMs appear to depend on the degree of progesterone receptor
      agonistic activity. 

PMID- 25596513
TI  - Response to Agilli and Aydin.

PMID- 25596514
TI  - The effect of bottom roughness on scalar transport in aquatic ecosystems:
      implications for reproduction and recruitment in the benthos.
AB  - Bottom roughness can influence gamete and larval transport in benthic organisms.
      For example the ratio of the roughness spacing (lambda) and roughness height (k)
      determines the type of roughness flow regime created in two dimensional (2D)
      flows: lambda/k<8 results in skimming flow; lambda/k~8 results in wake
      interference flow; and lambda/k>8 results in isolated roughness flow.
      Computational fluid dynamic modeling (COMSOL K-epsilon) was used to examine the
      effect of roughness geometry (e.g., a gradient in angularity provided by square,
      triangular and round 2D bottom roughness elements) on the prediction of roughness
      flow regime using biologically relevant lambda/k ratios. In addition, a
      continuously released scalar (a proxy for gametes and larvae) in a coupled
      convection-diffusion model was used to determine the relationship among roughness
      geometry, lambda/k ratios, and scalar transport (relative scalar transport,
      RT=ratio of scalar measured downstream in a series of roughness elements placed
      in tandem). The modeled roughness flow regimes fit closely with theoretical
      predictions using the square and triangle geometries, but the round geometry
      required a lower lambda/k ratio than expected for skimming flow. Relative
      transport of the scalar was consistent with the modeled flow regimes, however
      significant differences in RT were found among the roughness flows for each
      geometry, and significantly lower RT values were observed for skimming flow in
      the round geometry. The lambda/k ratio provides an accurate means of classifying
      flow in and around the roughness elements, whereas RT indicates the nature of
      scalar transport and retention. These results indicate that the spatial
      configuration of bottom roughness is an important determinant of gamete/larval
      transport in terms of whether the scalar will be retained among roughness
      elements or transported downstream. 

PMID- 25596515
TI  - On the sexual transmission dynamics of hepatitis B virus in China.
AB  - In a previous study we noticed that there might be co-infections of HBV and HIV
      by comparing incidence rates of these two diseases in China. The comparisons
      between the incidence data of HBV and sexually transmitted diseases (including
      AIDS, HIV, syphilis and gonorrhea) in China demonstrate that sexual transmission
      is an important route of spread of HBV in China. On the basis of this fact, in
      this paper we propose a compartmental model including under-aged children, male
      adults, and female adults. The effect of sexual transmission on the spread and
      prevalence of HBV in China is studied. The model is employed to simulate the HBV
      incidence data reported by the Chinese Center for Disease Control and Prevention
      for under-aged children, adult males, and adult females, respectively. The
      sensitivity analysis of the basic reproduction number indicates that it is
      important and crucial to increase the immunization rate for both under-aged
      children and adults in order to control the transmission of HBV in China. Our
      study suggests that effective control measures for hepatitis B in China include
      enhancing public education and awareness about hepatitis B virus, particularly
      about the fact that hepatitis B is a sexually transmitted disease, and increasing
      the immunization rate for both under-aged children and adults, especially for
      those groups of high risk. 

PMID- 25596516
TI  - Mathematical model of brain tumour with glia-neuron interactions and chemotherapy
      treatment.
AB  - In recent years, it became clear that a better understanding of the interactions
      among the main elements involved in the cancer network is necessary for the
      treatment of cancer and the suppression of cancer growth. In this work we propose
      a system of coupled differential equations that model brain tumour under
      treatment by chemotherapy, which considers interactions among the glial cells,
      the glioma, the neurons, and the chemotherapeutic agents. We study the conditions
      for the glioma growth to be eliminated, and identify values of the parameters for
      which the inhibition of the glioma growth is obtained with a minimal loss of
      healthy cells. 

PMID- 25596517
TI  - The role of induction in operant schedule performance.
AB  - Baum and Davison (2014b) showed that Baum's (2012) recasting of reinforcement as
      induction may be quantified by assuming that induction follows a power function
      of reinforcer rate. This power-function induction is readily integrated with
      theory based on the matching law. Herrnstein (1970) originally assumed background
      activities (BO) and their associated reinforcers ro to be constant, but ro should
      vary with BO. Further, power-function induction implies that BO should vary with
      reinforcer rate. Baum (1993) reported performance on a wide range of variable
      ratio (VR) and variable-interval (VI) schedules. Pigeons' VR peck rate followed
      an inverted U-shaped relation, but VI peck rate separated into three ranges of
      food rate: low-to-moderate, moderate-to-high, and extremely high. As food rate
      increases, the concave downward relation in the low range reaches an inflection
      point and gives way to a concave upward relation in the higher range. At the
      extremes of food rate, VI peck rate decreases. A model based on competition
      between induced pecking and BO accounted for VI peck rate in the moderate to
      extreme range of food rates. Further research will account for all three ranges,
      either by integrating power-function induction with matching theory or with a
      model based on competition between induced activities. 

PMID- 25596518
TI  - Pedicle perforator flaps for vulvar reconstruction--new generation of less
      invasive vulvar reconstruction with favorable results.
AB  - OBJECTIVES: Vulvar reconstruction after cancer surgery remains challenging.
      Pedicle perforator flaps are believed to be a less invasive option with better
      cosmesis. METHODS: A retrospective review identified 27 flaps in 16 patients who
      underwent vulvar reconstruction after cancer surgery using island pedicled
      perforator flaps. Their average age was 55.7+/-17.8 years (Range: 22-85). The
      average BMI was 23.5+/-4.0 (range: 18.8-28.5). Five of the 16 patients underwent
      unilateral vulvar reconstruction, and 11 of them underwent bilateral vulvar
      perineal reconstructions. The perforator flaps included deep femoral (profunda)
      artery perforator (DFAP or PAP) flaps (n=11), medial circumflex femoral
      perforator (MCFAP) flaps (n=8), external pudendal artery perforator (EPAP) flaps
      (n=2), medial thigh free style perforator flaps (n=2), and internal pudendal
      artery perforator flaps (n=4). RESULTS: All flaps survived with a 100% success
      rate. Three patients developed small wounds that required debridement and closure
      after the reconstruction. All donor sites were closed primarily. One patient
      developed temporary peroneal nerve palsy. During follow-up, none of the patients
      presented with donor site morbidities. All of the patients were satisfied with
      the cosmetic and functional results, except that one patient underwent a flap
      debulking procedure three months after surgery. CONCLUSIONS: Compared to
      traditional myocutaneous flaps, perforator flaps provide thinner fasciocutaneous
      flaps for vulvar reconstruction with favorable reconstruction results and fewer
      donor site morbidities. The medial or inner thigh is a region that is rich in
      perforators, which allow for more versatile flap design according to the defect.
      Furthermore, most of the donor site can be closed primarily without
      complications.

PMID- 25596519
TI  - Polymerase chain reaction-based serotyping of pathogenic bacteria in food.
AB  - Serotyping analysis of bacterial pathogens in food products is important for
      foodborne disease surveillance and outbreak investigations. Traditional
      immunological techniques are labor-intensive and time-consuming, whereas
      polymerase chain r eaction (PCR)-based techniques are more robust, consistent and
      rapid. PCR-based methods also provide easier standardization and better
      reproducibility. Here, we summarize some recent developments and applications of
      PCR-based serotyping for common foodborne pathogens, and provide a list of
      available bioinformatics tools for developing PCR-based serotyping assays. 

PMID- 25596520
TI  - Addition of thymidine to culture media for accurate examination of thymidine
      dependent small-colony variants of methicillin-resistant Staphylococcus aureus: a
      pilot study.
AB  - Small-colony variants (SCVs) are slow-growing subpopulations of various
      auxotrophic bacterial strains. Thymidine-dependent SCVs (TD-SCVs) are unable to
      synthesize thymidine; hence, these variants fail to grow in a medium without
      thymidine. In this study, we used 10 TD-SCVs of Staphylococcus aureus, of which
      four strains possessed mecA. We compared the efficacy of a newly modified medium
      containing thymidine for the detection of TD-SCVs of methicillin-resistant S.
      aureus (MRSA) to the efficacy of routinely used laboratory media. We observed
      that none of the 10 TD-SCVs of S. aureus grew in Mueller-Hinton agar, and four TD
      SCVs of MRSA failed to grow on all MRSA screening media, except for the ChromIDTM
      MRSA medium. Laboratory tests conducted using medium with thymidine incorporated
      showed that thymidine did not affect the minimum inhibitory concentrations of
      oxacillin and cefoxitin for clinical isolates of S. aureus, and was able to
      detect MRSA, including TD-SCVs. These findings showed that thymidine-incorporated
      media are able to detect TD-SCVs of MRSA without altering the properties of other
      clinically isolated MRSA strains. 

PMID- 25596522
TI  - Incidence and prognosis of ventricular arrhythmias in patients with congenital
      left ventricular aneurysms or diverticula.
AB  - BACKGROUND: Patients with congenital left ventricular aneurysms and diverticula
      may present with arrhythmia. The incidence of ventricular arrhythmias and the
      clinical outcome of these patients have not been reported to date. METHODS: Among
      250 consecutive patients with congenital left ventricular aneurysms and
      diverticula detected by echocardiography, the clinical outcome of patients who
      presented with ventricular arrhythmias or associated symptoms was investigated.
      RESULTS: Of 250 patients with congenital left ventricular aneurysms and
      diverticula, 30 had ventricular arrhythmias or syncope at initial presentation.
      During a follow-up of 85 months, spontaneous ventricular tachycardia occurred in
      17 of these patients (57%). Ventricular tachycardia was sustained in 13, with a
      monomorphic pattern in 9 patients. In 82% (11 patients), ventricular tachycardia
      was inducible during electrophysiologic testing. In 7 patients a sustained
      monomorphic ventricular tachycardia with a right bundle branch block pattern
      similar to the clinical tachycardia was induced. Twenty patients were treated
      with antiarrhythmic agents. Eleven patients received an implantable cardioverter
      defibrillator. Appropriate device discharges were observed in 73% during a follow
      up of 61 months. One patient underwent surgical resection of a congenital left
      ventricular aneurysm. Three patients underwent successful catheter ablation for
      incessant ventricular tachycardia. Of these, 2 were free of any clinically
      relevant arrhythmia during follow-up. Three patients died (10, 41, and 89 months
      after initial presentation). In 2 of them, the cause of death was attributed to
      ventricular arrhythmia. CONCLUSION: The clinical outcome of patients with
      congenital left ventricular aneurysms and diverticula and arrhythmia is variable.
      Clinical ventricular tachycardia in these patients is often monomorphic and
      usually inducible during electrophysiologic study, indicating a role for this
      test in risk stratification. Appropriate discharges are frequent in implantable
      cardioverter defibrillator recipients with congenital left ventricular aneurysms
      and diverticula.

PMID- 25596521
TI  - Decreases in bone mineral density at cortical and trabecular sites in the tibia
      and femur during the first year of spinal cord injury.
AB  - BACKGROUND: Disuse osteoporosis occurs in response to long-term immobilization.
      Spinal cord injury (SCI) leads to a form of disuse osteoporosis that only affects
      the paralyzed limbs. High rates of bone resorption after injury are evident from
      decreases in bone mineral content (BMC), which in the past have been attributed
      in the main to loss of trabecular bone in the epiphyses and cortical thinning in
      the shaft through endocortical resorption. METHODS: Patients with motor-complete
      SCI recruited from the Queen Elizabeth National Spinal Injuries Unit (Glasgow,
      UK) were scanned within 5weeks of injury (baseline) using peripheral Quantitative
      Computed Tomography (pQCT). Unilateral scans of the tibia, femur and radius
      provided separate estimates of trabecular and cortical bone parameters in the
      epiphyses and diaphyses, respectively. Using repeat pQCT scans at 4, 8 and
      12months post-injury, changes in BMC, bone mineral density (BMD) and cross
      sectional area (CSA) of the bone were quantified. RESULTS: Twenty-six subjects (5
      female, 21 male) with SCI (12 paraplegic, 14 tetraplegic), ranging from 16 to
      76years old, were enrolled onto the study. Repeated-measures analyses showed a
      significant effect of time since injury on key bone parameters at the epiphyses
      of the tibia and femur (BMC, total BMD, trabecular BMD) and their diaphyses (BMC,
      cortical BMD, cortical CSA). There was no significant effect of gender or age on
      key outcome measures, but there was a tendency for the female subjects to
      experience greater decreases in cortical BMD. The decreases in cortical BMD in
      the tibia and femur were found to be statistically significant in both men and
      women. CONCLUSIONS: By carrying out repeat pQCT scans at four-monthly intervals,
      this study provides a uniquely detailed description of the cortical bone changes
      that occur alongside trabecular bone changes in the first year of complete SCI.
      Significant decreases in BMD were recorded in both the cortical and trabecular
      bone compartments of the tibia and femur throughout the first year of injury.
      This study provides evidence for the need for targeted early intervention to
      preserve bone mass within this patient group.

PMID- 25596523
TI  - Back from the brink: catastrophic antiphospholipid syndrome.

PMID- 25596524
TI  - Clinical and molecular delineation of a 16p13.2p13.13 microduplication.
AB  - The 16p13.3p13.1 region has been reported as a "critical" hotspot region for
      recurrent microdeletions/duplications, which may contribute to epilepsy, learning
      difficulties and facial dysmorphisms. Cytogenetic and array-CGH analyses were
      performed because of the clinical characteristics of the patient. The girl showed
      de novo 16p13.3p13.13 duplication spanning a region of ~5.3 Mb. She presented
      brain anomalies, intellectual disability, epilepsy, facial and vertebral
      dysmorphisms. To our knowledge, this is the first reported case of 16p13.3p13.13
      duplication; only three patients with an overlapping deletion in 16p13.2p13.13
      were previously described. The duplicated region contains 21 OMIM genes and, six
      of them (RBFOX1, TMEM114, ABAT, PMM2, GRIN2A and, LITAF) were found to be
      associated with known diseases. Although no duplication of these genes has been
      described in the literature, we discuss here if they had some role in determining
      phenotype of our patient.

PMID- 25596526
TI  - Favorable modulation in neurotransmitters: effects of chronic anterior thalamic
      nuclei stimulation observed in epileptic monkeys.
AB  - Anterior thalamic nuclei (ATN) stimulation has been shown to be effective in
      seizure reduction. Nevertheless, the underlying mechanisms remain unclear. This
      study investigated the changes in the amino acid levels during chronic, single
      sided ATN-stimulation in the hippocampi of rhesus monkeys with mesial temporal
      lobe epilepsy induced by kainic acid (KA). The concentrations of glutamate, gamma
      aminobutyric acid, aspartate and taurine in the dialysates from bilateral
      hippocampi were determined at multiple time points using high-performance liquid
      chromatography. The results showed that after KA administration, the aspartate,
      gamma-aminobutyric acid and taurine levels increased significantly in the sham
      stimulation group, although the gamma-aminobutyric acid and taurine levels
      gradually returned to the basal levels in the chronic stage. The glutamate level
      showed an initial decrease in the acute stage and a subsequent increase in the
      chronic stage. Chronic ATN-stimulation reversed the increases in the glutamate
      and aspartate levels, and maintained the initial increases in the gamma
      aminobutyric acid and taurine levels till the end of the experiment. These amino
      acid levels, however, were not affected by either contralateral KA injection or
      contralateral ATN-stimulation, suggesting that the observed effects of ATN
      stimulation are restricted to the ipsilateral hemisphere. Our data suggest that
      chronic ATN-stimulation may induce favorable modulations in the amino acid levels
      in the hippocampi of epileptic monkeys, which may be an important mechanism
      underlying the effects of ATN-stimulation in epilepsy treatment. 

PMID- 25596525
TI  - 15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues,
      epilepsy and congenital heart disease: a series of 52 patients.
AB  - Proximal region of chromosome 15 long arm is rich in duplicons that, define five
      breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and
      BP2 has been previously associated with developmental delay and atypical
      psychological patterns. This region contains four highly-conserved and non
      imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the
      phenotypes associated with this microdeletion in a cohort of 52 patients. This
      copy number variation (CNV) was prevalent in 0.8% patients presenting with
      developmental delay, psychological pattern issues and/or multiple congenital
      malformations. This was studied by array-CGH at six different French Genetic
      laboratories. We collected data from 52 unrelated patients (including 3 foetuses)
      after excluding patients with an associated genetic alteration (known CNV,
      aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate
      developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4%
      had psychological issues such as Attention Deficit and Hyperactivity Disorder,
      Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted
      in 18.7% patients and associated congenital heart disease in 17.3%. Parents were
      analysed for abnormalities in the region in 65.4% families. Amongst these
      families, 'de novo' microdeletions were observed in 18.8% and 81.2% were
      inherited from one of the parents. Incomplete penetrance and variable
      expressivity were observed amongst the patients. Our results support the
      hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental
      delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The
      later feature has been rarely described. Incomplete penetrance and variability of
      expression demands further assessment and studies. 

PMID- 25596527
TI  - Zinc finger protein 407 (ZFP407) regulates insulin-stimulated glucose uptake and
      glucose transporter 4 (Glut4) mRNA.
AB  - The glucose transporter GLUT4 facilitates insulin-stimulated glucose uptake in
      peripheral tissues including adipose, muscle, and heart. GLUT4 function is
      impaired in obesity and type 2 diabetes leading to hyperglycemia and an increased
      risk of cardiovascular disease and neuropathy. To better understand the
      regulation of GLUT4 function, a targeted siRNA screen was performed and led to
      the discovery that ZFP407 regulates insulin-stimulated glucose uptake in
      adipocytes. The decrease in insulin-stimulated glucose uptake due to ZFP407
      deficiency was attributed to a reduction in GLUT4 mRNA and protein levels. The
      decrease in GLUT4 was due to both decreased transcription of Glut4 mRNA and
      decreased efficiency of Glut4 pre-mRNA splicing. Interestingly, ZFP407
      coordinately regulated this decrease in transcription with an increase in the
      stability of Glut4 mRNA, resulting in opposing effects on steady-state Glut4 mRNA
      levels. More broadly, transcriptome analysis revealed that ZFP407 regulates many
      peroxisome proliferator-activated receptor (PPAR) gamma target genes beyond
      Glut4. ZFP407 was required for the PPARgamma agonist rosiglitazone to increase
      Glut4 expression, but was not sufficient to increase expression of a PPARgamma
      target gene reporter construct. However, ZFP407 and PPARgamma co-overexpression
      synergistically activated a PPARgamma reporter construct beyond the level of
      PPARgamma alone. Thus, ZFP407 may represent a new modulator of the PPARgamma
      signaling pathway. 

PMID- 25596528
TI  - Inflammation and pyroptosis mediate muscle expansion in an interleukin-1beta (IL
      1beta)-dependent manner.
AB  - Muscle inflammation is often associated with its expansion. Bladder smooth muscle
      inflammation-induced cell death is accompanied by hyperplasia and hypertrophy as
      the primary cause for poor bladder function. In mice, DNA damage initiated by
      chemotherapeutic drug cyclophosphamide activated caspase 1 through the formation
      of the NLRP3 complex resulting in detrusor hyperplasia. A cyclophosphamide
      metabolite, acrolein, caused global DNA methylation and accumulation of DNA
      damage in a mouse model of bladder inflammation and in cultured bladder muscle
      cells. In correlation, global DNA methylation and NLRP3 expression was up
      regulated in human chronic bladder inflammatory tissues. The epigenetic silencing
      of DNA damage repair gene, Ogg1, could be reversed by the use of demethylating
      agents. In mice, demethylating agents reversed cyclophosphamide-induced bladder
      inflammation and detrusor expansion. The transgenic knock-out of Ogg1 in as few
      as 10% of the detrusor cells tripled the proliferation of the remaining wild type
      counterparts in an in vitro co-culture titration experiment. Antagonizing IL
      1beta with Anakinra, a rheumatoid arthritis therapeutic, prevented detrusor
      proliferation in conditioned media experiments as well as in a mouse model of
      bladder inflammation. Radiation treatment validated the role of DNA damage in the
      NLRP3-associated caspase 1-mediated IL-1beta secretory phenotype. A protein array
      analysis identified IGF1 to be downstream of IL-1beta signaling. IL-1beta-induced
      detrusor proliferation and hypertrophy could be reversed with the use of Anakinra
      as well as an IGF1 neutralizing antibody. IL-1beta antagonists in current
      clinical practice can exploit the revealed mechanism for DNA damage-mediated
      muscular expansion. 

PMID- 25596530
TI  - Conophylline protects cells in cellular models of neurodegenerative diseases by
      inducing mammalian target of rapamycin (mTOR)-independent autophagy.
AB  - Macroautophagy is a cellular response that leads to the bulk, nonspecific
      degradation of cytosolic components, including organelles. In recent years, it
      has been recognized that autophagy is essential for prevention of
      neurodegenerative diseases, including Parkinson disease (PD) and Huntington
      disease (HD). Here, we show that conophylline (CNP), a vinca alkaloid, induces
      autophagy in an mammalian target of rapamycin-independent manner. Using a
      cellular model of PD, CNP suppressed protein aggregation and protected cells from
      cell death caused by treatment with 1-methyl-4-phenylpyridinium, a neurotoxin, by
      inducing autophagy. Moreover, in the HD model, CNP also eliminated mutant
      huntingtin aggregates. Our findings demonstrate the possible use of CNP as a
      therapeutic drug for neurodegenerative disorders, including PD and HD. 

PMID- 25596529
TI  - Conditional knock-out reveals a requirement for O-linked N-Acetylglucosaminase (O
      GlcNAcase) in metabolic homeostasis.
AB  - O-GlcNAc cycling is maintained by the reciprocal activities of the O-GlcNAc
      transferase and the O-GlcNAcase (OGA) enzymes. O-GlcNAc transferase is
      responsible for O-GlcNAc addition to serine and threonine (Ser/Thr) residues and
      OGA for its removal. Although the Oga gene (MGEA5) is a documented human diabetes
      susceptibility locus, its role in maintaining insulin-glucose homeostasis is
      unclear. Here, we report a conditional disruption of the Oga gene in the mouse.
      The resulting homozygous Oga null (KO) animals lack OGA enzymatic activity and
      exhibit elevated levels of the O-GlcNAc modification. The Oga KO animals showed
      nearly complete perinatal lethality associated with low circulating glucose and
      low liver glycogen stores. Defective insulin-responsive GSK3beta phosphorylation
      was observed in both heterozygous (HET) and KO Oga animals. Although Oga HET
      animals were viable, they exhibited alterations in both transcription and
      metabolism. Transcriptome analysis using mouse embryonic fibroblasts revealed
      deregulation in the transcripts of both HET and KO animals specifically in genes
      associated with metabolism and growth. Additionally, metabolic profiling showed
      increased fat accumulation in HET and KO animals compared with WT, which was
      increased by a high fat diet. Reduced insulin sensitivity, glucose tolerance, and
      hyperleptinemia were also observed in HET and KO female mice. Notably, the
      respiratory exchange ratio of the HET animals was higher than that observed in WT
      animals, indicating the preferential utilization of glucose as an energy source.
      These results suggest that the loss of mouse OGA leads to defects in metabolic
      homeostasis culminating in obesity and insulin resistance. 

PMID- 25596532
TI  - Oxysterol-binding protein-related protein 8 (ORP8) increases sensitivity of
      hepatocellular carcinoma cells to Fas-mediated apoptosis.
AB  - Human hepatoma (HCC) has been reported to be strongly resistant to Fas-mediated
      apoptosis. However, the underlying mechanisms are poorly understood. In this
      study the function of oxysterol-binding protein-related protein 8 (ORP8) in human
      hepatoma cells apoptosis was assessed. We found that ORP8 is down-regulated,
      whereas miR-143, which controls ORP8 expression, is up-regulated in clinical HCC
      tissues as compared with liver tissue from healthy subjects. ORP8 overexpression
      triggered apoptosis in primary HCC cells and cell lines, which coincided with a
      relocation of cytoplasmic Fas to the cell plasma membrane and FasL up-regulation.
      Co-culture of HepG2 cells or primary HCC cells with Jurkat T-cells or T-cells,
      respectively, provided further evidence that ORP8 increases HCC cell sensitivity
      to Fas-mediated apoptosis. ORP8-induced Fas translocation is p53-dependent, and
      FasL was induced upon ORP8 overexpression via the endoplasmic reticulum stress
      response. Moreover, ORP8 overexpression and miR-143 inhibition markedly inhibited
      tumor growth in a HepG2 cell xenograft model. These results indicate that ORP8
      induces HCC cell apoptosis through the Fas/FasL pathway. The role of ORP8 in Fas
      translocation to the plasma membrane and its down-regulation by miR-143 offer a
      putative mechanistic explanation for HCC resistance to apoptosis. ORP8 may be a
      potential target for HCC therapy. 

PMID- 25596534
TI  - The concomitant management of cancer therapy and cardiac therapy.
AB  - Antitumor drugs have long been known to introduce a measurable risk of
      cardiovascular events. Cardio-Oncology is the discipline that builds on
      collaboration between cardiologists and oncologists and aims at screening,
      preventing or minimizing such a risk. Overt concern about "possible"
      cardiovascular toxicity might expose cancer patients to the risk of tumor
      undertreatment and poor oncologic outcome. Careful analysis of risk:benefit
      balance is therefore central to the management of patients exposed to potentially
      cardiotoxic drugs. Concomitant or sequential management of cardiac and cancer
      therapies should also be tailored to the following strengths and weaknesses: i)
      molecular mechanisms and clinical correlates of cardiotoxicity have been
      characterized to some extent for anthracyclines but not for other
      chemotherapeutics or new generation "targeted" drugs, ii) anthracyclines and
      targeted drugs cause different mechanisms of cardiotoxicity (type I versus type
      II), and this classification should guide strategies of primary or secondary
      prevention, iii) with anthracyclines and nonanthracycline chemotherapeutics,
      cardiovascular events may occur on treatment as well as years or decades after
      completing chemotherapy, iv) some patients may be predisposed to a higher risk of
      cardiac events but there is a lack of prospective studies that characterized
      optimal genetic tests and pharmacologic measures to minimize excess risk, v)
      clinical toxicity may be preceded by asymptomatic systolic and/or diastolic
      dysfunction that necessitates innovative mechanism-based pharmacologic treatment,
      and vi) patient-tailored pharmacologic correction of comorbidities is important
      for both primary and secondary prevention. Active collaboration of physicians
      with laboratory scientists is much needed for improving management of
      cardiovascular sequelae of antitumor therapy. This article is part of a Special
      Issue entitled: Membrane channels and transporters in cancers. 

PMID- 25596533
TI  - MicroRNA MiR-199a-5p regulates smooth muscle cell proliferation and morphology by
      targeting WNT2 signaling pathway.
AB  - MicroRNA miR-199a-5p impairs tight junction formation, leading to increased
      urothelial permeability in bladder pain syndrome. Now, using transcriptome
      analysis in urothelial TEU-2 cells, we implicate it in the regulation of cell
      cycle, cytoskeleton remodeling, TGF, and WNT signaling pathways. MiR-199a-5p is
      highly expressed in the smooth muscle layer of the bladder, and we altered its
      levels in bladder smooth muscle cells (SMCs) to validate the pathway analysis.
      Inhibition of miR-199a-5p with antimiR increased SMC proliferation, reduced cell
      size, and up-regulated miR-199a-5p targets, including WNT2. Overexpression of
      WNT2 protein or treating SMCs with recombinant WNT2 closely mimicked the miR-199a
      5p inhibition, whereas down-regulation of WNT2 in antimiR-expressing SMCs with
      shRNA restored cell phenotype and proliferation rates. Overexpression of miR-199a
      5p in the bladder SMCs significantly increased cell size and up-regulated SM22,
      SM alpha-actin, and SM myosin heavy chain mRNA and protein levels. These changes
      as well as increased expression of ACTG2, TGFB1I1, and CDKN1A were mediated by up
      regulation of the smooth muscle-specific transcriptional activator myocardin at
      mRNA and protein levels. Myocardin-related transcription factor A downstream
      targets Id3 and MYL9 were also induced. Up-regulation of myocardin was
      accompanied by down-regulation of WNT-dependent inhibitory Kruppel-like
      transcription factor 4 in miR-199a-5p-overexpressing cells. In contrast, Kruppel
      like transcription factor 4 was induced in antimiR-expressing cells following the
      activation of WNT2 signaling, leading to repression of myocardin-dependent genes.
      MiR-199a-5p plays a critical role in the WNT2-mediated regulation of
      proliferative and differentiation processes in the smooth muscle and may behave
      as a key modulator of smooth muscle hypertrophy, which is relevant for organ
      remodeling. 

PMID- 25596536
TI  - Patients admitted to hospital from care homes are at higher risk of dehydration,
      study finds.

PMID- 25596531
TI  - Changes in neuronal dopamine homeostasis following 1-methyl-4-phenylpyridinium
      (MPP+) exposure.
AB  - 1-Methyl-4-phenylpyridinium (MPP(+)), the active metabolite of the neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine, selectively kills dopaminergic
      neurons in vivo and in vitro via a variety of toxic mechanisms, including
      mitochondrial dysfunction, generation of peroxynitrite, induction of apoptosis,
      and oxidative stress due to disruption of vesicular dopamine (DA) storage. To
      investigate the effects of acute MPP(+) exposure on neuronal DA homeostasis, we
      measured stimulation-dependent DA release and non-exocytotic DA efflux from mouse
      striatal slices and extracellular, intracellular, and cytosolic DA (DAcyt) levels
      in cultured mouse ventral midbrain neurons. In acute striatal slices, MPP(+)
      exposure gradually decreased stimulation-dependent DA release, followed by
      massive DA efflux that was dependent on MPP(+) concentration, temperature, and DA
      uptake transporter activity. Similarly, in mouse midbrain neuronal cultures,
      MPP(+) depleted vesicular DA storage accompanied by an elevation of cytosolic and
      extracellular DA levels. In neuronal cell bodies, increased DAcyt was not due to
      transmitter leakage from synaptic vesicles but rather to competitive MPP(+)
      dependent inhibition of monoamine oxidase activity. Accordingly, monoamine
      oxidase blockers pargyline and l-deprenyl had no effect on DAcyt levels in MPP(+)
      treated cells and produced only a moderate effect on the survival of dopaminergic
      neurons treated with the toxin. In contrast, depletion of intracellular DA by
      blocking neurotransmitter synthesis resulted in ~30% reduction of MPP(+)-mediated
      toxicity, whereas overexpression of VMAT2 completely rescued dopaminergic
      neurons. These results demonstrate the utility of comprehensive analysis of DA
      metabolism using various electrochemical methods and reveal the complexity of the
      effects of MPP(+) on neuronal DA homeostasis and neurotoxicity. 

PMID- 25596537
TI  - Evidence to back dementia screening is still lacking, committee says.

PMID- 25596535
TI  - Estimating Cost-Effectiveness in Type 2 Diabetes: The Impact of Treatment
      Guidelines and Therapy Duration.
AB  - OBJECTIVES: Type 2 diabetes mellitus (T2DM) clinical guidelines focus on
      optimizing glucose control, with therapy escalation classically initiated within
      a "failure-based" regimen. Within many diabetes models, HbA1c therapy escalation
      thresholds play a pivotal role, controlling duration of therapy and,
      consequently, incremental costs and benefits. The objective of this study was to
      assess the relationship between therapy escalation threshold and time to therapy
      escalation on predicted cost-effectiveness of T2DM treatments. METHODS: This
      study used the Cardiff Diabetes Model to illustrate the relationship between
      costs and health outcomes associated with first-, second-, and third-line therapy
      as a function of time on each. Data from routine clinical practice were used to
      contrast predicted costs and health outcomes associated with guideline therapy
      escalation thresholds compared with clinical practice. The impact of baseline
      HbA1c and therapy escalation thresholds on cost-effectiveness was investigated,
      comparing a sodium/glucose cotransporter 2 inhibitor v. sulfonylurea added to
      metformin monotherapy. RESULTS: Lower thresholds are associated with a shorter
      time spent on monotherapy, ranging from 1.1 years (escalation at 6.5%) to 13
      years (escalation at 9.0%) and an increase in total lifetime cost of therapy.
      Treatment-related disutility is minimized with higher thresholds because
      progression to insulin is delayed. Using metformin combined with either
      dapagliflozin or a sulfonylurea to illustrate lower baseline HbA1c and/or higher
      therapy escalation thresholds was associated with increased cost-effectiveness
      ratios, driven by a longer duration of therapy. DISCUSSION: A marked difference
      in treatment cost-effectiveness was demonstrated when comparing routine clinical
      practice with guideline-advocated therapy escalation. This is important to both
      health care professionals and the wider health economic community with respect to
      understanding the true cost-effectiveness profile of any particular T2DM therapy
      option.

PMID- 25596538
TI  - Two drugs show promising results for treating hyperkalemia in US study.

PMID- 25596539
TI  - Letter to the Editor--Concern regarding adult congenital heart disease arrhythmia
      guidelines.

PMID- 25596540
TI  - New therapeutic options for advanced non-resectable malignant melanoma.
AB  - Melanoma is a malignant tumor which is inclined to metastasize promptly into the
      lymphatic system and other organs such as lung, liver, brain or bone. Therefore
      early diagnosis remains crucial for improving clinical outcome for melanoma
      patients. Current chemotherapy and chemo-immunotherapy regimes have shown little
      clinical benefit with no improvement in overall survival. However, new advances
      in melanoma biology such as the discovery of predisposed gene signatures and key
      somatic events have changed clinical practice. New therapeutic approaches are
      being tested or have been approved by the FDA/EMA recently including targeted
      therapies, such as BRAF- and MEK-inhibitors, and novel immunotherapies, such as
      anti-CTLA4 or anti-PD1 therapies. For these therapies an improvement of
      progression-free and overall survival has been seen in patients with advanced non
      resectable melanoma. The following review summarizes recent therapeutic options
      after the ASCO and ESMO annual meetings 2014 for the treatment of malignant
      melanoma. 

PMID- 25596541
TI  - Skipping across the tropics: the evolutionary history of sawtail surgeonfishes
      (Acanthuridae: Prionurus).
AB  - Fishes described as "anti-equatorial" have disjunct distributions, inhabiting
      temperate habitat patches on both sides of the tropics. Several alternative
      hypotheses suggest how and when species with disjunct distributions crossed
      uninhabitable areas, including: ancient vicariant events, competitive exclusion
      from the tropics, and more recent dispersal during Pliocene and Pleistocene
      glacial periods. Surgeonfishes in the genus Prionurus can provide novel insight
      into this pattern as its member species have disjunct distributions inhabiting
      either temperate latitudes, cold-water upwellings in the tropics, or low
      diversity tropical reef ecosystems. Here the evolutionary history and historical
      biogeography of Prionurus is examined using a dataset containing both
      mitochondrial and nuclear data for all seven extant species. Our results indicate
      that Prionurus is monophyletic and Miocene in origin. Several relationships
      remain problematic, including the placement of the Australian P. microlepidotus,
      and the relationship between P. laticlavius and P. punctatus. Equatorial
      divergence events between temperate western Pacific habitats occurred at least
      twice in Prionurus: once in the Miocene and again in the late Pliocene/early
      Pleistocene. Three species with tropical affinities, P. laticlavius, P.
      punctatus, and P. biafraensis, form a clade that originated in the Pliocene.
      These results suggest that a variety of mechanisms may regulate the disjunct
      distribution of temperate fishes, and provide support for both older and younger
      equatorial crossing events. They also suggest that interspecific competitive
      exclusion may be influential in fishes with "anti-equatorial" distributions. 

PMID- 25596542
TI  - Developmental nicotine exposure adversely effects respiratory patterning in the
      barbiturate anesthetized neonatal rat.
AB  - Neonates at risk for sudden infant death syndrome (SIDS) are hospitalized for
      cardiorespiratory monitoring however, monitoring is costly and generates large
      quantities of averaged data that serve as poor predictors of infant risk. In this
      study we used a traditional autocorrelation function (ACF) testing its
      suitability as a tool to detect subtle alterations in respiratory patterning in
      vivo. We applied the ACF to chest wall motion tracings obtained from rat pups in
      the period corresponding to the mid-to-end of the third trimester of human
      pregnancy. Pups were drawn from two groups: nicotine-exposed and saline-exposed
      at each age (i.e., P7, P8, P9, and P10). Respiratory-related motions of the chest
      wall were recorded in room air and in response to an arousal stimulus (FIO2 14%).
      The autocorrelation function was used to determine measures of breathing rate and
      respiratory patterning. Unlike alternative tools such as Poincare plots that
      depict an averaged difference in a measure breath to breath, the ACF when applied
      to a digitized chest wall trace yields an instantaneous sample of data points
      that can be used to compare (data) points at the same time in the next breath or
      in any subsequent number of breaths. The moment-to-moment evaluation of chest
      wall motion detected subtle differences in respiratory pattern in rat pups
      exposed to nicotine in utero and aged matched saline-exposed peers. The ACF can
      be applied online as well as to existing data sets and requires comparatively
      short sampling windows (~2 min). As shown here, the ACF could be used to identify
      factors that precipitate or minimize instability and thus, offers a quantitative
      measure of risk in vulnerable populations.

PMID- 25596543
TI  - Prenatal nicotine exposure increases hyperventilation in alpha4-knock-out mice
      during mild asphyxia.
AB  - Prenatal nicotine exposure alters breathing and ventilatory responses to stress
      through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the
      hypothesis that alpha4-containing nAChRs are involved in mediating the effects of
      prenatal nicotine exposure on ventilatory and metabolic responses to intermittent
      mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation
      (V(E)) and rate of O2 consumption ( V(O2)) of wild-type (WT) and alpha4-knock-out
      (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine
      exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed
      to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed
      with 2 min of air. Compared to WT, alpha4 KO mice had increased air V(E) and
      V(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the
      hyperventilatory response (increase in V(E)/V(O2)) to MA. At P1-2, nicotine
      suppressed air V(E) and V(O2) in both genotypes but did not affect the
      hyperventilatory response to MA. At P7-8 nicotine suppressed air V(E) and V(O2)
      of only alpha4 KO's but also significantly enhanced V(E) during MA (nearly double
      that of WT; p<0.001). This study has revealed complex effects of alpha4 nAChR
      deficiency and prenatal nicotine exposure on ventilatory and metabolic
      interactions and responses to stress.

PMID- 25596544
TI  - An examination of sources of sensitivity of consumer surplus estimates in travel
      cost models.
AB  - We examine sensitivity of estimates of recreation demand using the Travel Cost
      Method (TCM) to four factors. Three of the four have been routinely and widely
      discussed in the TCM literature: a) Poisson verses negative binomial regression;
      b) application of Englin correction to account for endogenous stratification; c)
      truncation of the data set to eliminate outliers. A fourth issue we address has
      not been widely modeled: the potential effect on recreation demand of the
      interaction between income and travel cost. We provide a straightforward
      comparison of all four factors, analyzing the impact of each on regression
      parameters and consumer surplus estimates. Truncation has a modest effect on
      estimates obtained from the Poisson models but a radical effect on the estimates
      obtained by way of the negative binomial. Inclusion of an income-travel cost
      interaction term generally produces a more conservative but not a statistically
      significantly different estimate of consumer surplus in both Poisson and negative
      binomial models. It also generates broader confidence intervals. Application of
      truncation, the Englin correction and the income-travel cost interaction produced
      the most conservative estimates of consumer surplus and eliminated the
      statistical difference between the Poisson and the negative binomial. Use of the
      income-travel cost interaction term reveals that for visitors who face relatively
      low travel costs, the relationship between income and travel demand is negative,
      while it is positive for those who face high travel costs. This provides an
      explanation of the ambiguities on the findings regarding the role of income
      widely observed in the TCM literature. Our results suggest that policies that
      reduce access to publicly owned resources inordinately impact local low income
      recreationists and are contrary to environmental justice. 

PMID- 25596545
TI  - Development and validation of sensitive kinetic spectrophotometric method for the
      determination of moxifloxacin antibiotic in pure and commercial tablets.
AB  - New, accurate, sensitive and reliable kinetic spectrophotometric method for the
      assay of moxifloxacin hydrochloride (MOXF) in pure form and pharmaceutical
      formulations has been developed. The method involves the oxidative coupling
      reaction of MOXF with 3-methyl-2-benzothiazolinone hydrazone hydrochloride
      monohydrate (MBTH) in the presence of Ce(IV) in an acidic medium to form colored
      product with lambda max at 623 and 660 nm. The reaction is followed
      spectrophotometrically by measuring the increase in absorbance at 623 nm as a
      function of time. The initial rate and fixed time methods were adopted for
      constructing the calibration curves. The linearity range was found to be 1.89
      40.0 MUg mL(-1) for initial rate and fixed time methods. The limit of detection
      for initial rate and fixed time methods is 0.644 and 0.043 MUg mL(-1),
      respectively. Molar absorptivity for the method was found to be 0.89*10(4) L mol(
      1) cm(-1). Statistical treatment of the experimental results indicates that the
      methods are precise and accurate. The proposed method has been applied
      successfully for the estimation of moxifloxacin hydrochloride in tablet dosage
      form with no interference from the excipients. The results are compared with the
      official method.

PMID- 25596547
TI  - Steroidogenic organ development and homeostasis: A WT1-centric view.
AB  - Adrenal and gonads are the main steroidogenic organs and are central to regulate
      body homeostasis in the vertebrate organism. Although adrenals and gonads are
      physically separated in the adult organism, both organs share a common
      developmental origin, the adrenogonadal primordium. One of the key genes involved
      in the development of both organs is the Wilms' tumor suppressor WT1, which
      encodes a zinc finger protein that has fascinated the scientific community for
      more than two decades. This review will provide an overview of the processes
      leading to the development of these unique organs with a particular focus on the
      multiple functions WT1 serves during adrenogonadal development. In addition, we
      will highlight some recent findings and open questions on how maintenance of
      steroidogenic organs is achieved in the adult organism. 

PMID- 25596546
TI  - In vitro lead exposure changes DNA methylation and expression of IGF2 and
      PEG1/MEST.
AB  - Epigenetic processes, such as changes in DNA methylation, likely mediate the link
      between environmental exposures in utero and altered gene expression.
      Differentially methylated regions (DMRs) that regulate imprinted genes may be
      especially vulnerable to environmental exposures since imprinting is established
      and maintained largely through DNA methylation, resulting in expression from only
      one parental chromosome. We used the human embryonic kidney cell line, HEK-293,
      to investigate the effects of exposure to physiologically relevant doses of lead
      acetate (Pb) on the methylation status of nine imprinted gene DMRs. We assessed
      mean methylation after seventy-two hours of Pb exposure (0-25 MUg/dL) using
      bisulfite pyrosequencing. The PEG1/MEST and IGF2 DMRs had maximum methylation
      decreases of 9.6% (20 MUg/dL; p<0.005) and 3.8% (25 MUg/dL; p<0.005),
      respectively. Changes at the MEG3 DMRs had a maximum decrease in methylation of
      2.9% (MEG3) and 1.8% (MEG3-IG) at 5 MUg/dL Pb, but were not statistically
      significant. The H19, NNAT, PEG3, PLAGL1, and SGCE/PEG10 DMRs showed a less than
      0.5% change in methylation, across the dose range used, and were deemed non
      responsive to Pb in our model. Pb exposure below reportable/actionable levels
      increased expression of PEG1/MEST concomitant with decreased methylation. These
      results suggest that Pb exposure can stably alter the regulatory capacity of
      multiple imprinted DMRs.

PMID- 25596548
TI  - Notch inhibits chondrogenic differentiation of mesenchymal progenitor cells by
      targeting Twist1.
AB  - While Notch signaling plays a critical role in the regulation of cartilage
      formation, its downstream targets are unknown. To address this we performed gain
      and losses of function experiments and demonstrate that Notch inhibition of
      chondrogenesis acts via up-regulation of the transcription factor Twist1. Upon
      Notch activation, murine limb bud mesenchymal progenitor cells in micromass
      culture displayed an inhibition of chondrogenesis. Twist1 was found to be
      exclusively expressed in mesenchymal progenitor cells at the onset stage of
      chondrogenesis during Notch activation. Inhibition of Notch signaling in these
      cells significantly reduced protein expression of Twist1. Furthermore, the
      inhibition effect of NICD1 on MPC chondrogenesis was markedly reduced by knocking
      down of Twist1. Constitutively active Notch signaling significantly enhanced
      Twist1 promoter activity; whereas mutation studies indicated that a putative
      NICD/RBPjK binding element in the promoter region is required for the Notch
      responsiveness of the Twist1 promoter. Finally, chromatin immunoprecipitation
      assays further confirmed that the Notch intracellular domain influences Twist1 by
      directly binding to the Twist1 promoter. These data provide a novel insight into
      understanding the molecular mechanisms behind Notch inhibition of the onset of
      chondrogenesis. 

PMID- 25596549
TI  - The mAb against adipocyte fatty acid-binding protein 2E4 attenuates the
      inflammation in the mouse model of high-fat diet-induced obesity via toll-like
      receptor 4 pathway.
AB  - Adipocyte fatty acid-binding protein (A-FABP) plays an important role in fatty
      acid-mediated processes and related metabolic and inflammatory responses. In this
      study, we prepared a novel monoclonal antibody against A-FABP, designated 2E4.
      Our data showed that 2E4 specifically binded to the recombinant A-FABP and native
      A-FABP of mice adipose tissue. Furthermore, we investigated the effect of 2E4 on
      metabolic and inflammatory responses in C57BL/6J obese mice fed on a high fat
      diet. 2E4 administration improved glucose response in high-fat-diet induced obese
      mice. The 2E4 treated groups exhibited lower free fatty acids, cholesterol, and
      triglycerides in a concentration-dependent manner. These changes were accompanied
      by down-regulated expression of pro-inflammatory cytokines in adipose tissue,
      including tumor necrosis factor alpha, monocyte chemotactic protein-1, and
      interleukin-6. Meanwhile, our data demonstrated that 2E4 significantly decreased
      the mRNA and protein levels of A-FABP in adipose tissue of mice. Further
      experiments showed that 2E4 notably suppressed the phosphorylation of
      IkappaBalpha and jun-N-terminal kinase through toll-like receptor 4 signaling
      pathway. Taken together, 2E4 is an effective monoclonal antibody against A-FABP,
      which attenuated the inflammatory responses induced in the high-fat-diet mice.
      These findings may provide scientific insight into the treatment of chronic low
      grade inflammation in obesity. 

PMID- 25596551
TI  - Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing
      ubiquitin/proteasome-mediated cFos protein degradation.
AB  - BACKGROUND: Andrographolide (Andro) is reported to inhibit hepatoma tumor growth
      in our previous studies. This study aims to further search the critical signals
      involved in such Andro-induced inhibition. METHODS: The anti-tumor effect of
      Andro was evaluated in vivo. Cancer PathwayFinder RT(2) ProfilerTM PCR array was
      used to find the altered genes. Real-time PCR was used to detect the mRNA
      expression. Protein expression was detected by Western-blot analysis, enzyme
      linked immunosorbent assay (ELISA) and immunohistochemical staining. Activator
      protein-1 (AP-1) transcriptional activity was detected by luciferase reporter
      assay. RESULTS: Andro (10mg/kg) inhibited hepatoma tumor growth in vivo. The
      expression of four genes decreased in Andro-treated tumor tissues. Among which,
      vascular endothelial growth factor (VEGFD) was the highest decreased gene. The
      decreased VEGFD expression was further confirmed by real-time PCR and
      immunohistochemical staining assay. Andro decreased VEGFD mRNA and protein
      expression in hepatoma Hep3B and HepG2 cells. Andro also decreased VEGFD amount
      in Hep3B cell supernatant. Andro decreased cFos protein expression and its
      translocation into nucleus, and also reduced AP-1 luciferase activity. Further
      results showed that Andro induced polyubiquitination of cFos. Proteasome
      inhibitor MG132 reversed the decreased expression of cFos protein, and the
      decreased mRNA and protein expression of VEGFD. SP600125, an inhibitor of c-Jun N
      terminal kinase (JNK), reversed the decreased expression of cFos and VEGFD
      induced by Andro. CONCLUSIONS: Andro decreased VEGFD expression in hepatoma
      cancer cells via inducing c-fos protein degradation, which will contribute to its
      anti-cancer activity, and JNK plays some roles in regulating this process.

PMID- 25596550
TI  - Extending kinome coverage by analysis of kinase inhibitor broad profiling data.
AB  - The explored kinome was extended with broad profiling using the DiscoveRx and
      Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors
      on 456 kinases in the DiscoveRx format delivered several insights. First, the
      coverage depended on the threshold of the selectivity parameter. Second, the
      relation between hit confirmation rates and inhibitor selectivity showed
      unexpectedly that higher selectivity can increase the likelihood of false
      positives. Third, comparing the coverage of a focused to that of a random library
      showed that the design based on a maximum number of scaffolds was superior to a
      limited number of scaffolds. Therefore, selective compounds can be used in target
      validation, enable the jumpstarting of new kinase drug discovery projects, and
      chart new biological space via phenotypic screening. 

PMID- 25596552
TI  - Effects of thin-film accelerated carbonation on steel slag leaching.
AB  - This paper discusses the effects of accelerated carbonation on the leaching
      behaviour of two types of stainless steel slags (electric arc furnace and argon
      oxygen decarburisation slag). The release of major elements and toxic metals both
      at the natural pH and at varying pH conditions was addressed. Geochemical
      modelling of the eluates was used to theoretically describe leaching and derive
      information about mineralogical changes induced by carbonation. Among the
      investigated elements, Ca and Si were most appreciably affected by carbonation. A
      very clear effect of carbonation on leaching was observed for silicate phases;
      geochemical modelling indicated that the Ca/Si ratio of Ca-controlling minerals
      shifted from ~ 1 for the untreated slag to 0.5-0.67 for the carbonated samples,
      thus showing that the carbonation process left some residual Ca-depleted silicate
      phases while the extracted Ca precipitated in the form of carbonate minerals. For
      toxic metals the changes in leaching induced by carbonation appeared to be mainly
      related to the resulting pH changes, which were as high as ~ 2 orders of
      magnitude upon carbonation. Depending on the specific shape of the respective
      solubility curves, the extent of leaching of toxic metals from the slag was
      differently affected by carbonation.

PMID- 25596553
TI  - Psychometric evaluation of the Gamblers' Beliefs Questionnaire with treatment
      seeking disordered gamblers.
AB  - Growing evidence for the efficacy of cognitive-behavioral therapy for disordered
      gambling supports the need for a comprehensive set of gambling-related assessment
      measures that have been validated with treatment-seeking samples. The Gamblers'
      Beliefs Questionnaire (GBQ) is a self-report measure that was designed to
      identify gambling-related cognitive distortions (Steenbergh, Meyers, May, &
      Whelan, 2002). In this study, the GBQ demonstrated good internal consistency and
      adequate construct validity in a treatment-seeking sample of disordered gamblers.
      Additionally, scores on the measure significantly decreased across a brief
      cognitive-behavioral treatment, providing validity support for use of the GBQ
      with a clinical population. 

PMID- 25596554
TI  - Potassium phosphite increases tolerance to UV-B in potato.
AB  - The use of biocompatible chemical compounds that enhance plant disease resistance
      through Induced Resistance (IR) is an innovative strategy to improve the yield
      and quality of crops. Phosphites (Phi), inorganic salts of phosphorous acid, are
      environment friendly, and have been described to induce disease control. Phi,
      similar to other plant inductors, are thought to be effective against different
      types of biotic and abiotic stress, and it is assumed that the underlying
      signaling pathways probably overlap and interact. The signaling pathways
      triggered by UV-B radiation, for instance, are known to crosstalk with other
      signaling routes that respond that biotic stress. In the present work, the effect
      of potassium phosphite (KPhi) pre-treatment on UV-B stress tolerance was
      evaluated in potato leaves. Plants were treated with KPhi and, after 3 days,
      exposed to 2 h/day of UV-B (1.5 Watt m(-2)) for 0, 3 and 6 days. KPhi pre
      treatment had a beneficial effect on two photosynthetic parameters, specifically
      chlorophyll content and expression of the psbA gene. Oxidative stress caused by
      UV-B was also prevented by KPhi. A decrease in the accumulation of hydrogen
      peroxide (H2O2) in leaves and an increase in guaiacol peroxidase (POD) and
      superoxide dismutase (SOD) activities were also observed. In addition, the
      expression levels of a gene involved in flavonoid synthesis increased in UV-B
      stressed plants only when pre-treated with KPhi. Finally, accumulation of
      glucanases and chitinases was induced by UV-B stress and markedly potentiated by
      KPhi pre-treatment. Altogether, this is the first report that shows a
      contribution of KPhi in UV-B stress tolerance in potato plants.

PMID- 25596555
TI  - Technical note: Headspace analysis of explosive compounds using a novel sampling
      chamber.
AB  - The development of instruments and methods for explosive vapor detection is a
      continually evolving field of interest. A thorough understanding of the
      characteristic vapor signatures of explosive material is imperative for the
      development and testing of new and current detectors. In this research a
      headspace sampling chamber was designed to contain explosive materials for the
      controlled, reproducible sampling and characterization of vapors associated with
      these materials. In a detonation test, the chamber was shown to contain an
      explosion equivalent to three grams of trinitrotoluene (TNT) without damage to
      the chamber. The efficacy of the chamber in controlled headspace sampling was
      evaluated in laboratory tests with bulk explosive materials. Small quantities of
      TNT, triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD)
      were separately placed in the sampling chamber, and the headspace of each
      material was analyzed by gas chromatography/mass spectrometry (GC/MS) with online
      cryogenic trapping to yield characteristic vapor signatures for each explosive
      compound. Chamber sampling conditions, temperature and sampling time, were varied
      to demonstrate suitability for precise headspace analysis. 

PMID- 25596556
TI  - Preliminary results of sequential monitoring of simulated clandestine graves in
      Colombia, South America, using ground penetrating radar and botany.
AB  - In most Latin American countries there are significant numbers of missing people
      and forced disappearances, 68,000 alone currently in Colombia. Successful
      detection of shallow buried human remains by forensic search teams is difficult
      in varying terrain and climates. This research has created three simulated
      clandestine burial styles at two different depths commonly encountered in Latin
      America to gain knowledge of optimum forensic geophysics detection techniques.
      Repeated monitoring of the graves post-burial was undertaken by ground
      penetrating radar. Radar survey 2D profile results show reasonable detection of
      1/2 clothed pig cadavers up to 19 weeks of burial, with decreasing confidence
      after this time. Simulated burials using skeletonized human remains were not able
      to be imaged after 19 weeks of burial, with beheaded and burnt human remains not
      being able to be detected throughout the survey period. Horizontal radar time
      slices showed good early results up to 19 weeks of burial as more area was
      covered and bi-directional surveys were collected, but these decreased in
      amplitude over time. Deeper burials were all harder to image than shallower ones.
      Analysis of excavated soil found soil moisture content almost double compared to
      those reported from temperate climate studies. Vegetation variations over the
      simulated graves were also noted which would provide promising indicators for
      grave detection. 

PMID- 25596557
TI  - Investigating a common approach to DNA profile interpretation using probabilistic
      software.
AB  - Recently there has been a drive for standardisation of DNA profile interpretation
      within and between different forensic laboratories. The continuous interpretation
      software STRmixTM has been adopted for use by laboratories in Australia and New
      Zealand for profile interpretation. Within this paper we examine the concordance
      in profile interpretation of three crime samples by twenty different analysts
      across twelve different international laboratories using STRmixTM. The three
      profiles selected for this study exhibited a range of template and complexity.
      The use of probabilistic software has compelled a level of concordance between
      different analysts however there remain differences within profile
      interpretation, particularly with the objective assignment of the number of
      contributors to profiles.

PMID- 25596558
TI  - A simple and label-free aptasensor based on nickel hexacyanoferrate nanoparticles
      as signal probe for highly sensitive detection of 17beta-estradiol.
AB  - A simple and label-free electrochemical aptasensor was developed for detecting
      17beta-estradiol (E2). To translate the binding events between aptamer and E2
      into the measurable electrochemical signal, the nickel hexacyanoferrate
      nanoparticles (NiHCF NPs) as signal probe was in situ introduced on the electrode
      by a simple two-step deposition method, exhibiting well-defined peaks with good
      stability and reproducibility. Subsequently, Au nanoparticles (Au NPs) was
      covered on the NiHCF NPs, which not only provided a platform for immobilizing the
      aptamer by S-Au interaction, but further enhanced the conductivity and stability
      of the signal probe. With the addition of E2, the formation of E2-aptamer
      complexes on the sensing interface retarded the interfacial electron transfer
      reaction of the probe, resulting in the decrease of the electrochemical signal.
      E2 could be readily examined by measuring the signal change. A linear range of
      1*10(-12)-6*10(-10) M was obtained with a low detection limit of 0.8*10(-12) M.
      The aptasensor also exhibited high specificity to E2 in control experiments
      employing seven endocrine disrupting compounds as the interferents that had
      similar structure or coexisted with E2 in the environment. Besides, the
      applicability of the aptasensor was successfully evaluated by determining E2 in
      the real samples.

PMID- 25596559
TI  - Colorimetric detection of single nucleotide polymorphisms in the presence of 103
      fold excess of a wild-type gene.
AB  - Herein, we proposed a simple colorimetric assay for highly sensitive and specific
      detection of single nucleotide polymorphisms (SNPs). Briefly, SNP specific
      capture probes (CPs) were immobilized onto magnetic beads. The hybridization of a
      target SNP with the CPs and detection probes containing multiple DNAzyme
      sequences (DNAzyme-DPs) brought the target SNP and the DNAzyme-DPs onto the
      magnetic beads. Meanwhile, a mismatch-specific CEL II enzyme (Surveyor((r))
      nuclease) cleaved the imperfectly hybridized wild-type gene together with all
      other mismatched sequences off the magnetic beads, leaving only the perfectly
      matched SNP strands on the magnetic beads. Amplified colorimetric detection was
      carried out through the DNAzyme-catalyzed oxidation of 3,3',5,5'
      tetramethylbenzidine in the presence of H2O2. The excellent selectivity of
      Surveyor((r)) nuclease toward all imperfectly-matched DNA duplexes produced an
      ultrahigh selectivity - one mutant in 1000 copies of the wild-type gene can be
      detected. In addition, the cumulative nature of the DNAzyme-amplified signal
      generation process produced a detection limit as low as 0.40 fM and a dynamic
      range from 1.0 to 200 fM. The simple protocol and its high sensitivity and
      selectivity allowed the proposed assay to be used in the detection of SNPs in
      genomic DNA samples.

PMID- 25596560
TI  - Reversibly crosslinked hyaluronic acid nanoparticles for active targeting and
      intelligent delivery of doxorubicin to drug resistant CD44+ human breast tumor
      xenografts.
AB  - The existence of drug resistance poses a major obstacle for the treatment of
      various malignant human cancers. Here, we report on reduction-sensitive
      reversibly crosslinked hyaluronic acid (HA) nanoparticles based on HA-Lys-LA
      conjugates (Lys: l-lysine methyl ester, LA: lipoic acid) for active targeting
      delivery of doxorubicin (DOX) to CD44+ breast cancers in vitro and in vivo,
      effectively overcoming drug resistance (ADR). HA-Lys-LA with degrees of
      substitution of 5, 10 and 28% formed robust nano-sized nanoparticles (152-219nm)
      following auto-crosslinking. DOX-loaded crosslinked nanoparticles revealed
      inhibited DOX release under physiological conditions while fast drug release in
      the presence of 10mM glutathione (GSH). Notably, MTT assays showed that DOX
      loaded crosslinked HA-Lys-LA10 nanoparticles possessed an apparent targetability
      and a superior antitumor activity toward CD44 receptor overexpressing DOX
      resistant MCF-7 human breast cancer cells (MCF-7/ADR). The in vivo
      pharmacokinetics and biodistribution studies in MCF-7/ADR tumor xenografts in
      nude mice showed that DOX-loaded crosslinked HA-Lys-LA10 nanoparticles had a
      prolonged circulation time and a remarkably high accumulation in the tumor
      (12.71%ID/g). Notably, DOX-loaded crosslinked HA-Lys-LA10 nanoparticles exhibited
      effective inhibition of tumor growth while continuous tumor growth was observed
      for mice treated with free drug. The Kaplan-Meier survival curves showed that in
      contrast to control groups, all mice treated with DOX-loaded crosslinked HA-Lys
      LA10 nanoparticles survived over an experimental period of 44days. Importantly,
      DOX-loaded crosslinked HA nanoparticles caused low side effects. The reversibly
      crosslinked hyaluronic acid nanoparticles with excellent biocompatibility, CD44
      targetability, and effective reversal of drug resistance have a great potential
      in cancer therapy. 

PMID- 25596562
TI  - Treatment of halogenated phenolic compounds by sequential tri-metal reduction and
      laccase-catalytic oxidation.
AB  - Halogenated phenolic compounds (HPCs) are exerting negative effects on human
      beings and ecological health. Zero-valence metal reduction can dehalogenate HPCs
      rapidly but cannot mineralize them. Enzymatic catalysis can oxidize phenolic
      compounds but fails to dehalogenate efficiently, and sometimes even produces more
      toxic products. In this study, [Fe|Ni|Cu] tri-metallic reduction (TMR) and
      laccase-catalytic oxidation (LCO) processes were combined to sequentially remove
      HPCs, including triclosan, tetrabromobisphenol A, and 2-bromo-4-fluorophenol in
      water. The kinetics, pH and temperature dependences of TMR and LCO were obtained.
      The detailed TMR, LCO, and TMR-LCO transformation pathways of three HPCs were
      well described based on the identification of intermediate products and frontier
      molecular orbitals (FMOs) theory. The results showed that the two-stage process
      worked synergically: TMR that reductively dehalogenated HPCs followed by LCO that
      completely removed dehalogenated products. TMR was proven to not only improve
      biodegradability of HPCs but also reduce the yield of potential carcinogenic by
      products. Furthermore, a TMR-LCO flow reactor was assembled and launched for 256
      h, during which >95% HPCs and >75% TOC were removed. Meanwhile, monitored by
      microorganism indicators, 83.2%-92.7% acute toxicity of HPCs was eliminated, and
      the genotoxicity, produced by LCO, was also avoided by using TMR as pretreatment
      process. 

PMID- 25596561
TI  - Mechanism of synergy of BH3 mimetics and paclitaxel in chronic myeloid leukemia
      cells: Mcl-1 inhibition.
AB  - Paclitaxel is an alternative chemotherapeutic agent for chronic myelogenous
      leukemia (CML) when primary or secondary resistance of tyrosine kinase inhibitors
      (TKI) is emerging, because paclitaxel could bypass the apoptotic deficiencies
      linked to p53 and fas ligand pathways in CML. However, high levels of Bcl-2
      family proteins in CML could resist paclitaxel-induced apoptosis. Herein, we
      utilized two BH3 mimetics ABT-737 and S1 to study the potential of BH3 mimetics
      in combination with paclitaxel in treatment of CML cells and illustrated the
      mechanism by which BH3 mimetics synergize with paclitaxel. As a single agent, S1
      could induce apoptosis in CML-derived cell line K562, whereas ABT-737 was largely
      ineffective. However, both of the two agents could efficiently synergize with
      paclitaxel through intrinsic apoptosis pathway. By using Bcl-2 siRNA, Bcl-XL
      siRNA or Mcl-1 siRNA, we found although each of the three members exhibited
      activities to block paclitaxel-induced apoptosis, Mcl-1 was the determinant for
      the synergistic effect between paclitaxel and ABT-737 or S1. Furthermore,
      paclitaxel/ABT737 synergized to drastically upregulate Bim to displace Bak from
      Mcl-1, whereas S1 directly binds Mcl-1 to release both Bim and Bak. As such, ABT
      737 and S1 sensitized CML to paclitaxel by Mcl-1 inhibition, indirect inhibition
      through Bim antagonizing Mcl-1, or direct inhibition through binding to Mcl-1
      itself. Finally, activation of JNK/Bim pathway was identified as the apical
      mechanism for ABT-737/paclitaxel synergism. Together, our results demonstrated
      potent synergy between BH3 mimetics and paclitaxel in the killing of CML cells
      and revealed an important role for Mcl-1 in mediating synergism by these agents. 

PMID- 25596564
TI  - Free advice for young scientists to design research projects.

PMID- 25596563
TI  - Arrhythmias and pacing.

PMID- 25596565
TI  - Impact of sporadic reporting of poultry Salmonella serovars from selected
      developing countries.
AB  - This review documents the sporadic reporting of poultry Salmonella serovars in
      South Africa, Egypt, Indonesia, India, and Romania, five countries selected based
      on the importance of their distribution in different regions of the world and
      their cumulative significant population size of 1.6 billion. South Africa
      reported contamination of its poultry carcasses by S. Hadar, S. Blockley, S.
      Irumu, and S. Anatum. Results from Egypt showed that S. Enteritidis and S.
      Typhimurium were predominant in poultry along with other non-typhoid strains,
      namely S. Infantis, S. Kentucky, S. Tsevie, S. Chiredzi, and S. Heidelberg. In
      Indonesia, the isolation of Salmonella Typhi was the main focus, while other
      serovars included S. Kentucky, S. Typhimurium, and S. Paratyhi C. In India, S.
      Bareilly was predominant compared to S. Enteritidis, S. Typhimurium, S. Paratyphi
      B, S. Cerro, S. Mbandaka, S. Molade, S. Kottbus, and S. Gallinarum. Romania
      reported two Salmonella serovars in poultry that affect humans, namely S.
      Enteritidis and S. Typhimurium, and other non-typhoid strains including S.
      Infantis, S. Derby, S. Colindale, S. Rissen, S. Ruzizi, S. Virchow, S.
      Brandenburg, S. Bredeney, S. Muenchen, S. Kortrijk, and S. Calabar. The results
      showed the spread of different serovars of Salmonella in those five developing
      countries, which is alarming and emphasizes the urgent need for the World Health
      Organization Global Foodborne Infections Network (WHO-GFN) to expand its
      activities to include more strategic participation and partnership with most
      developing countries in order to protect poultry and humans from the serious
      health impact of salmonellosis. 

PMID- 25596566
TI  - The role of vitamin D in malaria.
AB  - An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in
      patients with malaria infection. A role for vitamin D in malaria has been
      suggested by many studies. Genetic studies have identified numerous factors that
      link vitamin D to malaria, including human leukocyte antigen genes, toll-like
      receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4,
      nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D
      has also been implicated in malaria via its effects on the Bacillus Calmette
      Guerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase
      pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase.
      Vitamin D may be important in malaria; therefore, additional research on its role
      in malaria is needed. 

PMID- 25596567
TI  - Developing countries: health round-trip.
AB  - International travel can pose various risks to health, depending both on the
      health needs of the traveller and on the type of travel to be undertaken.
      Travellers intending to visit a destination in a developing country should
      consult a travel medicine clinic or medical practitioner before the journey.
      General precautions can greatly reduce the risk of exposure to infectious agents.
      Vaccination is a highly effective method of preventing certain infectious
      diseases. The aim of this study is to know the risks involved and the best way to
      prevent them. 

PMID- 25596568
TI  - Potential spread of multidrug-resistant coagulase-negative staphylococci through
      healthcare waste.
AB  - INTRODUCTION: Healthcare waste (HCW) might potentially harbor infective viable
      microorganisms in sanitary landfills. We investigated the antimicrobial
      susceptibility patterns and the occurrence of the mecA gene in coagulase-negative
      Staphylococcus strains (CoNS) recovered from the leachate of the HCW in an
      untreated sanitary landfill. METHODOLOGY: Bacterial identification was performed
      by physiological and molecular approaches, and minimum inhibitory concentrations
      (MICs) of antimicrobial drugs were determined by the agar dilution method
      according to CLSI guidelines. All oxacillin-resistant bacteria were screened for
      the mecA gene. RESULTS: Out of 73 CoNS, seven different species were identified
      by 16S rDNA sequencing: Staphylococcus felis (64.4%; n = 47), Staphylococcus
      sciuri (26.0%; n = 19), Staphylococcus epidermidis (2.7%; n = 2), Staphylococcus
      warneri (2.7%; n = 2), Staphylococcus lentus (1.4%; n = 1), Staphylococcus
      saprophyticus (1.4%; n = 1), and Staphylococcus haemolyticus (1.4%; n = 1).
      Penicillin was the least effective antimicrobial (60.3% of resistance; n = 44)
      followed by erythromycin (39.8%; n = 29), azithromycin (28.8%; n = 21), and
      oxacillin (16.5%; n = 12). The most effective drug was vancomycin, for which no
      resistance was observed, followed by gentamicin and levofloxacin, for which only
      intermediate resistance was observed (22%, n = 16 and 1.4%, n = 1, respectively).
      Among the oxacillin-resistant strains, the mecA gene was detected in two
      isolates. CONCLUSIONS: Considering the high antimicrobial resistance observed,
      our results raise concerns about the survival of putative bacterial pathogens
      carrying important resistance markers in HCW and their environmental spread
      through untreated residues discharged in sanitary landfills.

PMID- 25596569
TI  - Antibiotic susceptibility and prevalence of foodborne pathogens in poultry meat
      in Romania.
AB  - INTRODUCTION: The occurrence of pathogenic strains in poultry meat is of growing
      concern in Romania. Another problem found on a global level is the continuous
      increase of antimicrobial resistance in bacteria isolated from food. This study
      aimed to evaluate the prevalence of pathogenic bacteria in poultry carcasses
      obtained in Romania in 2012-2013 and to reveal the most prevalent patterns of
      antimicrobial resistance in the isolated strains. METHODOLOGY: A total of 144
      broiler chicken carcasses were evaluated according to classical microbiological
      methods. The DNA was extracted from the bacterial colonies and the resistance
      genes were identified by PCR. RESULTS: In 2012, 47.2% of the samples revealed at
      least one of the following bacteria: Campylobacter jejuni (9.72%; n = 7),
      Salmonella enterica serotype Enteritidis (4.17%; n = 3), Listeria monocytogenes
      (15.28%; n = 11), and Escherichia coli (16.67%; n = 12). In 2013, the number of
      positive samples of pathogenic bacteria decreased, although Campylobacter jejuni
      was isolated in a higher percentage (20.8% vs. 9.72%). The percentage of
      multidrug-resistant (MDR) bacteria was high (23%); the most prevalent pattern
      included resistance to tetracycline, sulfonamides, and
      quinolones/fluoroquinolones. All the resistant Salmonella and E. coli strains
      were tested for the presence of characteristic resistance genes (Kn, bla(TEM),
      tetA, tetB, tetG, DfrIa, aadA1a, Sul) and revealed that these isolates represent
      an important reservoir in the spread of this phenomenon. CONCLUSIONS: Our
      findings suggest that Romania urgently needs an integrated surveillance system
      within the entire chain, for drug-resistant pathogens isolated from poultry meat.

PMID- 25596570
TI  - Effectiveness of the Bacillus Calmette-Guerin vaccine in an Indonesian population
      with D543N NRAMP1 polymorphism.
AB  - INTRODUCTION: Bacille Calmette-Guerin (BCG) vaccination remains a routine
      immunization in primary care in tuberculosis (TB)-endemic areas, though several
      studies found that its efficacy was inconclusive. Natural resistance-asociated
      machrophage protein 1 (NRAMP1) polymorphism has been shown to result in higher
      susceptibility to TB. Information on genetic susceptibility in populations will
      be useful in planning the application of the BCG vaccine. The present study
      explored BCG efficacy in a rural Timor population with specific NRAMP1
      polymorphism in a TB-endemic region of eastern Indonesia. METHODOLOGY: A case
      control study with 64 newly diagnosed pulmonary TB patients and 65 healthy
      controls was performed. BCG scars were examined by a physician. NRAMP1
      polymorphism was evaluated using molecular methods. RESULTS: Half of the subjects
      (65; 50.4%) had a clear presenting BCG scar on the upper arm, suggesting a
      successful BCG vaccination. Among the subjects, D543N NRAMP1 polymorphism,
      history of contact with TB patients, and not having a clear BCG scar on the upper
      arm tended to be significantly association with active TB. The significant
      differences were more profound when subjects were divided based on presenting BCG
      scar. Subjects without clear BCG scars had significant association with
      developing TB disease (p = 0.014). In multivariate analysis, history of previous
      contact with TB patients and unclear presenting BCG scar were associated with
      active TB (OR 9.2; 2.0-43.8 95% CI, OR 4.8; 2.1-11.0 95% CI, respectively).
      CONCLUSIONS: BCG vaccination in our population was effective for TB protection,
      especially in highly endemic areas of TB, regardless genetic susceptibility.

PMID- 25596571
TI  - Could there be an association between chronic brucellosis and endothelial damage?
AB  - INTRODUCTION: In this study, we examined the effects of Brucella infection on
      endothelial dysfunction. Flow-mediated dilatation (FMD) measurement is indicator
      of the endothelial function, and abnormal values indicating endothelial
      dysfunction are accepted as the first stage of atherosclerosis. METHODOLOGY:
      Twenty-four patients who had been treated for acute brucellosis two years before,
      and who had had no relapses in the follow-up, were prospectively included in the
      study, along with 30 healthy individuals in the control group. RESULTS: While the
      highly sensitive C-reactive protein (hs-CRP) value was 2.42 +/- 1.45 in the
      patient group, it was 1.72 +/- 0.61 in the control group (p = 0.025). While the
      FMD value was 3.50 +/- 1.58 in the patient group, it was 5.88 +/- 1.88 in the
      control group (p < 0.001). While the percentage increase in FMD was 9.88 +/- 4.92
      in the patient group, it was 17.49 +/- 6.3 in the control group (p < 0.001). It
      was observed that FMD value, the percentage increase in FMD, and basal radius
      were correlated with hs-CRP (r = -0.644, p < 0.001; r = - 0.558, p = 0.002; r =
      0.444, p = 0.018, respectively). The carotid artery intima media thickness (IMT)
      value was found to be 0.61 +/- 0.17 in the patient group and 0.49 +/- 0.12 in the
      control group (p = 0.004). CONCLUSIONS: The abnormal FMD and IMT values observed
      in brucellosis patients might be an indicator of more frequent arterial
      dysfunction, increased cardiovascular risk, and atherosclerosis.

PMID- 25596572
TI  - A protocol for microbiologically safe preparation, storage, and use of autologous
      serum eye-drops in low-income countries.
AB  - INTRODUCTION: The study aimed to investigate whether the preparation, storage,
      and use of autologous serum in insulin syringes is microbiologically safe.
      METHODOLOGY: Blood samples (10 mL) were obtained from 10 volunteers. After
      centrifugation, the supernatant serum was removed and distributed in 5 sterile
      insulin syringes for each sample; syringes were numbered 0 to 4 and labelled with
      the subject's details. Syringes were immediately transported to the microbiology
      laboratory and stored in a refrigerator at +4 degrees C. The "0" labelled
      syringes were separated from the others and 100 ul of serum from each syringe was
      immediately seeded on chocolate and Sabouraud agar plates, which were incubated
      aerobically at 37 degrees C for 96 hours to detect any bacterial and/or fungal
      contamination. In the next 4 days, the same procedure was repeated for the
      remaining syringes: on day 1, the "1" labelled syringes were analyzed; on day 2,
      the "2" labelled ones, and so on. In a second experiment, blood samples were
      obtained from 5 different volunteers. The same procedure as above was followed,
      but each syringe was used for repeated cultures at 2-hour intervals, for a total
      of 12 cultures/day. The needle was removed and replaced for each inoculation and
      the syringes were stored in the refrigerator after use. RESULTS: Under these
      experimental conditions, none of the cultures showed microbial growth.
      CONCLUSIONS: Results suggest that, under the protocol described, preparation,
      storage and use of undiluted autologous serum in insulin syringes is inexpensive,
      fast, and microbiologically safe. This is of great importance for low-income
      countries.

PMID- 25596573
TI  - Prevalence of opportunistic infections in HIV-positive patients in Bahrain: a
      four-year review (2009-2013).
AB  - INTRODUCTION: This study aimed to examine the prevalence of opportunistic
      infections in HIV-infected patients in Bahrain and its relation to absolute CD4
      count, CD4%, and CD4/CD8 ratio. METHODOLOGY: This retrospective cohort study used
      laboratory records (January 2009 - May 2013) from a major hospital in Bahrain.
      Opportunistic infections (OIs); absolute CD4 counts, CD4%, and CD4/CD8 ratio were
      recorded. RESULTS: CD4% and absolute CD4 count in HIV patients with associated
      infections (157 +/- 295) was significantly lower than in those without associated
      infections (471 +/- 285) (p < 0.001). There was no significant difference in
      CD4/CD8 ratio between the two groups. Infection with Staphylococcus aureus was
      the commonest infection, present in 9.8% of total HIV-infected patients and 28.7%
      of members of the AIDS patient group with OIs, followed by yeast infections (9.2%
      and 27.2%, respectively). Mycobacterium tuberculosis was present in 3.6% of total
      HIV-infected patients and 10.6% of the group with OIs, while mycobacteria other
      than tuberculosis (MOTT) was present in 2.5% and 7.5%, respectively. Pneumocystis
      jirovecii pneumonia (PCP) was observed in 5.1% and 15.1%, respectively. Herpes
      simplex II (HSV-II) was observed in 3% and 9%, respectively, while
      Cytomegalovirus antigenemia was only present in 2% and 6%, respectively.
      Streptococcus pneumoniae, Streptococcus milleri, Stenotrophomonas maltophilia,
      and Citrobacter species were bacterial infections observed least frequently.
      CONCLUSIONS: Studying the pattern of OIs in HIV-infected patients in Bahrain is
      of paramount importance due to the scarcity of data in the Arab world. This will
      help to improve physicians' awareness to improve care of HIV-infected patients.

PMID- 25596574
TI  - Abdominal cystic echinococcosis in Bangladesh: a hospital-based study.
AB  - INTRODUCTION: Cystic echinococcosis (CE) is reported from nearly all geographic
      areas of Bangladesh, but little information is available on its epidemiologic and
      clinical features. The aim of this study was to describe the clinical
      manifestations of hepatic and abdominal CE cases presenting to tertiary referral
      hospitals in Dhaka, Bangladesh. METHODOLOGY: A retrospective study was conducted
      via chart reviews of hepatic and abdominal CE patients under care at tertiary
      referral hospitals in Dhaka, Bangladesh, between 2002 and 2011. Age, sex,
      education level, occupation, urban versus rural residence, drinking water source,
      history of dog ownership, cyst type and location, and clinical manifestations
      were recorded for all patients. RESULTS: Of the 130 patients enrolled, 92 (70.8%)
      were female and 38 (29.2%) were male. The majority of patients were from rural
      (76.2%) rather than urban (23.8%) areas. All cases were from the northern part of
      the country, with no cases reported from the south or southeast. Most patients
      were between 21 and 40 years of age. A total of 119 patients (91.5%) had cysts
      only in the liver, with the remaining 8.5% having cysts in both the liver and
      lungs or in the abdominal cavity. Seventy-six (58.5%) of the hepatic cysts were
      stage CE1, indicating recent infection. CONCLUSIONS: Active transmission of
      Echinococcus granulosus appears to be occurring in Bangladesh, as indicated by
      the high number of CE1 hepatic cysts seen at tertiary care hospitals. Community
      ultrasound screening studies are warranted to better define the distribution of
      cases and risk factors for parasite transmission.

PMID- 25596575
TI  - A bibliometric study of international scientific productivity in giardiasis
      covering the period 1971-2010.
AB  - INTRODUCTION: Despite years of relative neglect, interest in Giardia infection
      seems to be recently growing, perhaps in part due to its inclusion into the World
      Health Organization's Neglected Diseases Initiative since 2004. The purpose of
      this study was to provide an overview of Giardia and giardiasis research over
      time, as represented by the quantity of published papers. METHODOLOGY: Data for
      this study were collected from the electronic PubMed/Medline database of National
      Library of Medicine's (NLM), due to it is easily accessibility and wide use. It
      was accessed online between April and December 2011. Data for the period 1971
      2010 were obtained and information was downloaded using the EndNote program
      developed by Thomson Reuters. RESULTS: During the study period, a total of 6,964
      references (articles, reviews, editorials, letter to the editor, etc.) covering
      different aspects of Giardia and giardiasis were located in the PubMed database
      after applying the search strategy reported above. Most papers were original
      articles and published in English. CONCLUSIONS: In this first effort to explore
      the development and research productivity on giardiasis over time (no previously
      published bibliometric studies on giardiasis exist), two interesting
      characteristics of the Giardia and giardiasis literature were discovered: the
      concentration of papers over journals disseminating the research results, and
      that research in this field is growing and will likely continue to grow in the
      coming years.

PMID- 25596576
TI  - Prevalence and associated risk factors of Toxoplasma gondii in female farmworkers
      of southeastern Turkey.
AB  - INTRODUCTION: There are a limited number of studies of the agricultural
      population about the prevalence of Toxoplasma gondii (T. gondii) infection
      throughout the world. The aim of this study was to determine the prevalence and
      risk factors of toxoplasmosis in female farmworkers in the southeastern region of
      Turkey. METHODOLOGY: The optimum sample size was determined using the Epi Info
      Program, and blood samples were collected from 684 women of reproductive age.
      Serum samples were analyzed by qualitative and quantitative methods for anti-T.
      gondii IgG and IgM antibodies with a commercially available enzyme immunoassay.
      Questionnaires through which socio-demographic information was collected were
      applied during face-to-face interviews of subjects who gave their consent to
      participate in the study. Crude odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated, and Chi-square analyses and logistic regression were
      performed. RESULTS: Of the 684 women, the prevalence of toxoplasmosis was
      determined to be 58.3% and 1% for IgG and IgM, respectively. Employment as a
      seasonal farmworker, increasing age, and having had three or more pregnancies
      were found to be the crucial associated risk factors that affect the prevalence
      of T. gondii infection (p < 0.05). In contrast to these, the provincial
      development level was found to be a confounding factor. There was no association
      between toxoplasmosis and household size, education attainment, and poverty in
      the bivariate analyses. CONCLUSIONS: The findings show that control and
      serological screening programs should be implemented nationwide in Turkey for the
      reliable and fast detection of congenital Toxoplasma infections.

PMID- 25596577
TI  - Antibiotic use in Albania between 2011 and 2012.
AB  - INTRODUCTION: Health institutions in Albania have recently reported an increase
      in antibiotic misuse and microbial resistance. Until now, there have been no
      comprehensive studies that analyzed the overall use of antibiotics in Albania.
      The aim of this study was to analyze the overall antibiotic use in Albania
      between 2011 and 2012, using standardized methodology of measurement, based on
      World Health Organization guidelines. METHODOLOGY: Data from 2011 and 2012 on
      antibiotic use from ambulatory and hospital sector were examined. Antibiotics
      were divided based on anatomic therapeutic chemical classification. Defined daily
      dose (DDD) for each drug was assigned, and DDD per 1,000 inhabitants per day
      (DID) was used as a measurement unit. In cases of antibiotic combinations for
      which DDD were not available, unit doses were assigned. RESULTS: In 2011-2012,
      total antibiotic use decreased from 24.25 to 20.66 DID. Penicillin's were the
      most used antibiotic class, with 10.62 DID (2011) and 10.51 DID (2012).
      Tetracycline use decreased from 5.45 DID (2011) to 0.98 DID (2012). Macrolides
      increased from 1.36 to 1.88 DID, quinolones from 1.72 to 2.51 DID. The overall
      antibiotic use was significantly higher than the reimbursed antibiotic use - 3.17
      DID (2011) and 2.79 DID (2012) - based on the official data for the same period.
      CONCLUSIONS: This study enables policymakers to further analyze the quality of
      antibiotic prescriptions and draw comparisons to other countries. The analyzed
      data suggest there are different factors influencing out-of-pocket use of
      antibiotics and wrongly prescribed antibiotics. Further studies are necessary to
      evaluate these factors.

PMID- 25596579
TI  - Prevalence, patterns, and factors associated with bleeding tendencies in dengue.
AB  - INTRODUCTION: The pattern of bleeding tendencies in dengue and its corellation
      with platelet count and other factors requires clarification. METHODOLOGY: A
      retrospective study on bleeding tendencies in adults with dengue and platelet
      counts of less than 100,000 per mm(3) was conducted. Factors associated with
      bleeding were analyzed. The study cohort were grouped as dengue with severe
      thrombocytopenia when platelet count was < 50,000/mm(3) and as dengue with
      moderate thrombocytopenia if platelet count was 50,000-100,000/mm(3) RESULTS: A
      total of 638 patients formed the study cohort. A 24.1% prevalence of bleeding
      tendencies was observed. Prior anti-platelet drug intake, platelet count of <
      70,000/mm(3), international normalized ratio > 2.0, and partial thromboplastin
      time > 60 seconds were associated with bleeding. Esophagogastroduodenoscopy was
      found to identify structural gastroduodenal lesions when dengue was complicated
      by hematemesis or melena. CONCLUSIONS: The results of this study suggest that
      bleeding complications in dengue can occur at platelet counts of up to
      70,000/mm(3), and that prior anti-platelet drug intake increases bleeding risk.
      Evaluation of hematemesis or melena in dengue with esophagogastroduodenoscopy is
      beneficial.

PMID- 25596578
TI  - Occurrence and antimicrobial susceptibility of Salmonella isolates recovered from
      the pig slaughter process in Romania.
AB  - INTRODUCTION: Reported human salmonellosis cases have increased in Romania.
      Antibiotic susceptibility testing of Salmonella strains isolated from pork and
      chicken meat indicate a worrying multidrug resistance pattern. This study aimed
      to investigate the occurrence of Salmonella and to evaluate the antibiotic
      resistance of Salmonella strains in a pig slaughterhouse-processing complex,
      which receives animals from 30% of the large industrialized swine farms in
      Romania. METHODOLOGY: A total of 108 samples, including pork (n = 47), packaged
      pork products (n = 44), scald water sludge (n = 8), and detritus from the hair
      removal machine of the slaughterhouse (n = 9) were examined for the presence of
      Salmonella through standard methods. The antibiotic susceptibility of the
      isolated strains to 17 antibiotics was tested using the Vitek 2 system. RESULTS:
      Twenty-six (24.1%) samples were found to be Salmonella positive; this included
      25.5% of meat samples and 15.9% of packaged products, as well as samples from two
      different points of the slaughter (41.2%). Resistance was observed against
      tetracycline (61.5%), ampicillin (50%), piperacillin (50%), trimethoprim
      sulfamethoxazole (34.6%), amoxicillin/clavulanic acid (26.9%), nitrofurantion
      (23.1%), cefazolin (15.4%), piperacillin/tazobactam (7.7%), imipenem (3.8%),
      ciprofloxacin (3.8%), and norfloxacin (3.8%). No resistance towards cefoxitin,
      cefotaxime, ceftazidime, cefepime, amikacin, and gentamicin was found.
      CONCLUSIONS: Our study demonstrated the occurrence of multidrug-resistant
      Salmonella strains in the investigated pork production complex and highlighted it
      as a potential source of human infections. The results demonstrate the
      seriousness of antibiotic resistance of Salmonella in Romania, while providing a
      useful insight for the treatment of human salmonellosis by specialists.

PMID- 25596580
TI  - The prevalence of Trichuris spp. infection in indoor and outdoor cats on St.
      Kitts.
AB  - INTRODUCTION: The present study was conducted to evaluate the prevalence of
      Trichuris spp. and other intestinal parasitic infections in owned cats on St.
      Kitts. METHODOLOGY: The feces of 41 non-feral cats (23 indoor only; 18
      indoor/outdoor) were examined for the presence of Trichuris spp. eggs. RESULTS:
      Nine (22%) of the cats were positive for Trichuris spp. Prevalence of
      trichuriasis in indoor cats was 26.0% as compared to 16.7% in outdoor cats. Other
      parasites identified included Ancylostoma spp. (10%; 4 cats), Toxocara cati (2%;
      1 cat), Platynosomum spp. (22%; 9 cats), Mammomonogamus spp. (2%; 1 cat) and
      coccidia (7%; 3 cats). CONCLUSION: On St. Kitts, indoor cats are as likely to
      have parasite infections as outdoor cats. Given the zoonotic potential of some of
      the identified parasites, periodical anthelmintic treatment should be provided to
      both indoor and outdoor cats.

PMID- 25596582
TI  - Treatment of tularemia during pregnancy.

PMID- 25596581
TI  - A case of imported neurocysticercosis in Portugal.
AB  - Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in
      resource-poor countries. We report the case of a 24-year-old woman born and
      residing in Guinea-Bissau, who was transferred to Portugal two months after the
      onset of a possible meningitis (fever, headache, seizures, and coma) that did not
      respond to antibiotic treatment. The diagnosis of NCC was confirmed by MR
      imaging, which showed multiple lesions compatible with cysticercus, and by
      polymerase chain reaction (PCR) of the cerebrospinal fluid. After 28 days on
      albendazole and dexamethasone without improvement, she was started on
      praziquantel, which she completed in six weeks with progressive recovery. 

PMID- 25596584
TI  - China to stop using organs from executed prisoners for transplantations.

PMID- 25596583
TI  - Worldwide spread of NDM-1: are migratory birds culprits?

PMID- 25596585
TI  - Treatment effects and placebo effects.

PMID- 25596586
TI  - Health & Demographic Surveillance System Profile: The Nairobi Urban Health and
      Demographic Surveillance System (NUHDSS).
AB  - The Nairobi Urban Health and Demographic Surveillance System (NUHDSS) was the
      first urban-based longitudinal health and demographic surveillance platform in
      sub-Saharan Africa (SSA). The NUHDSS was established in 2002 to provide a
      platform to investigate the long-term social, economic and health consequences of
      urban residence, and to serve as a primary research tool for intervention and
      impact evaluation studies focusing on the needs of the urban poor in SSA. Since
      its inception, the NUHDSS has successfully followed every year a population of
      about 65,000 individuals in 24,000 households in two slum communities--Korogocho
      and Viwandani--in Nairobi, Kenya. Data collected include key demographic and
      health information (births, deaths including verbal autopsy, in- and out
      migration, immunization) and other information that characterizes living
      conditions in the slums (livelihood opportunities, household amenities and
      possessions, type of housing etc.). In addition to the routine data, it has
      provided a robust platform for nesting several studies examining the challenges
      of rapid urbanization in SSA and associated health and poverty dynamics. NUHDSS
      data are shared through internal and external collaborations, in accordance with
      the Centre's guidelines for publications, data sharing.

PMID- 25596588
TI  - Altered Functionality, Morphology, and Vesicular Glutamate Transporter Expression
      of Cortical Motor Neurons from a Presymptomatic Mouse Model of Amyotrophic
      Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the
      gradual degeneration of motor neurons in the cerebrospinal axis. Whether upper
      motor neuron hyperexcitability, which is a feature of ALS, provokes dysfunction
      of glutamate metabolism and degeneration of lower motor neurons via an
      anterograde process is undetermined. To examine whether early changes in upper
      motor neuron activity occur in association with glutamatergic alterations, we
      performed whole-cell patch-clamp recordings to analyze excitatory properties of
      Layer V cortical motor neurons and excitatory postsynaptic currents (EPSCs) in
      presymptomatic G93A mice modeling familial ALS (fALS). We found that G93A Layer V
      pyramidal neurons exhibited altered EPSC frequency and rheobase values indicative
      of their hyperexcitability status. Biocytin loading of these hyperexcitable
      neurons revealed an expansion of their basal dendrite arborization. Moreover, we
      detected increased expression levels of the vesicular glutamate transporter 2 in
      cortical Layer V of G93A mice. Altogether our data show that functional and
      structural neuronal alterations associate with abnormal glutamatergic activity in
      motor cortex of presymptomatic G93A mice. These abnormalities, expected to
      enhance glutamate release and to favor its accumulation in the motor cortex,
      provide strong support for the view that upper motor neurons are involved early
      on in the pathogenesis of ALS. 

PMID- 25596587
TI  - Thalamocortical Connectivity Predicts Cognition in Children Born Preterm.
AB  - Thalamocortical connections are: essential for brain function, established early
      in development, and significantly impaired following preterm birth. Impaired
      cognitive abilities in preterm infants may be related to disruptions in
      thalamocortical connectivity. The aim of this study was to test the hypothesis:
      thalamocortical connectivity in the preterm brain at term-equivalent is
      correlated with cognitive performance in early childhood. We examined 57 infants
      who were born <35 weeks gestational age (GA) and had no evidence of focal
      abnormality on magnetic resonance imaging (MRI). Infants underwent diffusion MRI
      at term and cognitive performance at 2 years was assessed using the Bayley III
      scales of Infant and Toddler development. Cognitive scores at 2 years were
      correlated with structural connectivity between the thalamus and extensive
      cortical regions at term. Mean thalamocortical connectivity across the whole
      cortex explained 11% of the variance in cognitive scores at 2 years. The
      inclusion of GA at birth and parental socioeconomic group in the model explained
      30% of the variance in subsequent cognitive performance. Identifying impairments
      in thalamocortical connectivity as early as term equivalent can help identify
      those infants at risk of subsequent cognitive delay and may be useful to assess
      efficacy of potential treatments at an early age. 

PMID- 25596589
TI  - Dopaminergic Modulation of Cognitive Preparation for Overt Reading: Evidence from
      the Study of Genetic Polymorphisms.
AB  - Choosing and implementing the rules for contextually adequate behavior depends on
      frontostriatal interactions. Observations in Parkinson's disease and
      pharmacological manipulations of dopamine transmission suggest that these
      corticobasal loops are modulated by dopamine. To determine, therefore, the
      physiological contributions of dopamine to task-rule-related processing, we
      performed a cue-target fMRI reading paradigm in 71 healthy participants and
      investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1
      polymorphisms. The DRD2/ANKK1 polymorphism did not affect results. Intermediate
      prefrontal dopamine concentrations in COMT Val158Met heterozygotes facilitated
      preparatory interactions between the mesial prefrontal cortex and the left
      striatum during preparation for overt reading. To our knowledge, this is the
      first report of an inverted U-shaped curve modulation of cognition-related brain
      activity by prefrontal dopamine levels. In contrast, a linear effect of COMT
      Val158Met and DAT1 VNTR 9/10 polymorphisms on preparatory activity in the left
      inferior frontal gyrus pointed to a negative interaction between tonic lateral
      prefrontal and phasic subcortical dopamine. The COMT Val158Met polymorphism
      affected also feedforward and feedback processing in the sensorimotor speech
      system. Our results suggest that dopamine modulates corticobasal interactions on
      both the cortical and subcortical level but differently depending on the specific
      cognitive subprocesses involved. 

PMID- 25596591
TI  - Attentional Enhancement of Auditory Mismatch Responses: a DCM/MEG Study.
AB  - Despite similar behavioral effects, attention and expectation influence evoked
      responses differently: Attention typically enhances event-related responses,
      whereas expectation reduces them. This dissociation has been reconciled under
      predictive coding, where prediction errors are weighted by precision associated
      with attentional modulation. Here, we tested the predictive coding account of
      attention and expectation using magnetoencephalography and modeling. Temporal
      attention and sensory expectation were orthogonally manipulated in an auditory
      mismatch paradigm, revealing opposing effects on evoked response amplitude.
      Mismatch negativity (MMN) was enhanced by attention, speaking against its
      supposedly pre-attentive nature. This interaction effect was modeled in a
      canonical microcircuit using dynamic causal modeling, comparing models with
      modulation of extrinsic and intrinsic connectivity at different levels of the
      auditory hierarchy. While MMN was explained by recursive interplay of sensory
      predictions and prediction errors, attention was linked to the gain of inhibitory
      interneurons, consistent with its modulation of sensory precision. 

PMID- 25596590
TI  - Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display
      Profound Degeneration in the Absence of UCHL1 Function.
AB  - Corticospinal motor neurons (CSMN) receive, integrate, and relay cerebral
      cortex's input toward spinal targets to initiate and modulate voluntary movement.
      CSMN degeneration is central for numerous motor neuron disorders and
      neurodegenerative diseases. Previously, 5 patients with mutations in the
      ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) gene were reported to have
      neurodegeneration and motor neuron dysfunction with upper motor neuron
      involvement. To investigate the role of UCHL1 on CSMN health and stability, we
      used both in vivo and in vitro approaches, and took advantage of the
      Uchl1(nm3419) (UCHL1(-/-)) mice, which lack all UCHL1 function. We report a
      unique role of UCHL1 in maintaining CSMN viability and cellular integrity. CSMN
      show early, selective, progressive, and profound cell loss in the absence of
      UCHL1. CSMN degeneration, evident even at pre-symptomatic stages by
      disintegration of the apical dendrite and spine loss, is mediated via increased
      ER stress. These findings bring a novel understanding to the basis of CSMN
      vulnerability, and suggest UCHL1(-/-) mice as a tool to study CSMN pathology. 

PMID- 25596592
TI  - Neural Systems Involved When Attending to a Speaker.
AB  - Remembering what a speaker said depends on attention. During conversational
      speech, the emphasis is on working memory, but listening to a lecture encourages
      episodic memory encoding. With simultaneous interference from background speech,
      the need for auditory vigilance increases. We recreated these context-dependent
      demands on auditory attention in 2 ways. The first was to require participants to
      attend to one speaker in either the absence or presence of a distracting
      background speaker. The second was to alter the task demand, requiring either an
      immediate or delayed recall of the content of the attended speech. Across 2 fMRI
      studies, common activated regions associated with segregating attended from
      unattended speech were the right anterior insula and adjacent frontal operculum
      (aI/FOp), the left planum temporale, and the precuneus. In contrast, activity in
      a ventral right frontoparietal system was dependent on both the task demand and
      the presence of a competing speaker. Additional multivariate analyses identified
      other domain-general frontoparietal systems, where activity increased during
      attentive listening but was modulated little by the need for speech stream
      segregation in the presence of 2 speakers. These results make predictions about
      impairments in attentive listening in different communicative contexts following
      focal or diffuse brain pathology. 

PMID- 25596595
TI  - Changes coming to pregnancy labeling.

PMID- 25596596
TI  - Know what's in airplane's emergency medical kit, two pharmacists say.

PMID- 25596593
TI  - Topologically Reorganized Connectivity Architecture of Default-Mode, Executive
      Control, and Salience Networks across Working Memory Task Loads.
AB  - The human brain is topologically organized into a set of spatially distributed,
      functionally specific networks. Of these networks, the default-mode network
      (DMN), executive-control network (ECN), and salience network (SN) have received
      the most attention recently for their vital roles in cognitive functions.
      However, very little is known about whether and how the interactions within and
      between these 3 networks would be modulated by cognitive demands. Here, we
      employed graph-based modularity analysis to identify the DMN, ECN, and SN during
      an N-back working memory (WM) task and further investigated the modulation of
      intra- and inter-network interactions at different cognitive loads. As the task
      load elevated, functional connectivity decreased within the DMN while increased
      within the ECN, and the SN connected more with both the DMN and ECN. Within
      network connectivity of the ventral and dorsal posterior cingulate cortex was
      differentially modulated by cognitive load. Further, the superior parietal
      regions in the ECN showed increased internetwork connections at higher WM loads,
      and these increases correlated positively with WM task performance. Together,
      these findings advance our understanding of dynamic integrations of specialized
      brain systems in response to cognitive demands and may serve as a baseline for
      assessing potential disruptions of these interactions in pathological conditions.

PMID- 25596598
TI  - New drug and biological product approvals, 2014.

PMID- 25596600
TI  - Using administrative data for your research project: 10 considerations before you
      begin.
AB  - With increasing pressure to conduct research during residency training, and given
      the availability of administrative claims data, pharmacy residents will likely
      consider using large administrative databases for their research project. With
      competing time commitments and the short duration of residencies, residents and
      their preceptors must consider the 10 factors outlined above in order to produce
      a thoughtful, clinically relevant research project. While this discussion focused
      on the completion of a residency research project, these topics are also relevant
      to a broader pharmacy audience. Colleges of pharmacy are increasingly requiring
      research projects as part of their curriculum, and pharmacy students and
      practitioners often consider obtaining additional degrees requiring a research
      component. Both students and practitioners can use the guidance provided herein
      when planning research projects and investigations to aid in the successful
      completion of research using administrative claims data.

PMID- 25596594
TI  - Prefrontal Cortical Inactivations Decrease Willingness to Expend Cognitive Effort
      on a Rodent Cost/Benefit Decision-Making Task.
AB  - Personal success often necessitates expending greater effort for greater reward
      but, equally important, also requires judicious use of our limited cognitive
      resources (e.g., attention). Previous animal models have shown that the prelimbic
      (PL) and infralimbic (IL) regions of the prefrontal cortex (PFC) are not involved
      in (physical) effort-based choice, whereas human studies have demonstrated PFC
      contributions to (mental) effort. Here, we utilize the rat Cognitive Effort Task
      (rCET) to probe PFC's role in effort-based decision making. In the rCET, animals
      can choose either an easy trial, where the attentional demand is low but the
      reward (sugar) is small or a difficult trial on which both the attentional demand
      and reward are greater. Temporary inactivation of PL and IL decreased all
      animals' willingness to expend mental effort and increased animals'
      distractibility; PL inactivations more substantially affected performance (i.e.,
      attention), whereas IL inactivations increased motor impulsivity. These data
      imply that the PFC contributes to attentional resources, and when these resources
      are diminished, animals shift their choice (via other brain regions) accordingly.
      Thus, one novel therapeutic approach to deficits in effort expenditure may be to
      focus on the resources that such decision making requires, rather than the
      decision-making process per se. 

PMID- 25596601
TI  - Antiinfective therapy for pregnant or lactating patients in the emergency
      department.
AB  - PURPOSE: Special considerations in pharmacotherapy for infectious diseases in
      pregnant and lactating women in the emergency department (ED) setting are
      reviewed. SUMMARY: With many women turning to the ED as a source of primary care,
      it is essential for pharmacists involved in providing ED services to guide the
      selection of appropriate antiinfective agents during pregnancy and lactation;
      this area of practice is complicated by the very limited body of published data
      on the safety and efficacy of maternal antimicrobial use and potential fetal or
      neonatal adverse effects. Infectious diseases commonly encountered in the ED
      include sexually transmitted diseases, bacterial vaginosis and other vaginal
      infections, respiratory and urinary tract infections, and pneumonia. Recommended
      first-line therapies for pregnant or lactating women may differ from those
      recommended for other patient populations. Although some widely used
      antiinfective classes and agents are generally considered safe for use in
      pregnant women, others (e.g., clarithromycin, fluoroquinolones) have been linked
      to birth defects and neonatal adverse effects. In addition to guiding ED
      practitioners in the appropriate use of antiinfective agents in pregnant women
      and nursing mothers, pharmacists can reinforce the importance of appropriate
      follow-up care (including specialist referral or culture testing in some cases)
      and ongoing preventive health measures such as vaccine administration.
      CONCLUSION: The use of antiinfective agents in pregnant or lactating women
      requires consideration not only of the drugs' effectiveness but also their
      possible effects on the fetus or newborn and the nature of follow-up care.
      References are available to help clinicians make treatment decisions.

PMID- 25596603
TI  - Use of low-dose prothrombin complex concentrate before lumbar puncture.
AB  - PURPOSE: The use of an off-label dose of four-factor prothrombin complex
      concentrate (PCC) for International Normalized Ratio (INR) reversal in a patient
      before a diagnostic lumbar puncture is reported. SUMMARY: A 57-year-old, 122-kg
      man arrived at the hospital with a possible diagnosis of meningitis and had an
      INR of >3 while on warfarin therapy. The patient initiated warfarin therapy in
      2009 due to recurrent deep vein thrombosis. The patient required reversal of his
      elevated INR in order for a lumbar puncture to be safely performed (INR must be
      no higher than 1.4). Multiple units of fresh frozen plasma (FFP) were
      administered, with a subsequent INR decrease to 1.9. Additional units of FFP were
      given. The patient developed respiratory decompensation due to volume overload,
      partially caused by the administration of multiple units of FFP. As the INR
      remained above 1.4 but was less than 2, an alternative dosing strategy was used.
      A dose of 1020 units of factor IX, equaling about 10 mg/kg based on a maximum
      dosing weight of 100 kg, was administered. The two vials of PCC administered each
      contained 510 units of factor IX. No vitamin K was given. The patient's INR,
      checked 30 minutes after PCC administration, was 1.3, and the lumbar puncture was
      performed. The lumbar puncture was completed without complication, and the
      patient was restarted on therapeutic anticoagulation the following day.
      CONCLUSION: A 57-year-old patient was successfully treated with low-dose PCC to
      reverse an INR from 1.7 to 1.3 in order to perform a diagnostic lumbar puncture.

PMID- 25596602
TI  - Desensitization to ceftaroline in a patient with multiple medication
      hypersensitivity reactions.
AB  - PURPOSE: The case of a patient with multiple medication hypersensitivity
      reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who
      underwent desensitization to ceftaroline is reported. SUMMARY: A 32-year-old
      Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and
      major depression was admitted for MRSA cellulitis with a subcutaneous abscess
      along the left sternomanubrial joint and clavicular osteomyelitis secondary to
      port placement after gastric bypass surgery. The patient had an extensive history
      of hypersensitivity reactions. Pertinent documented allergies were as follows:
      penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid
      (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The
      patient also reported previous reactions to aztreonam (unknown) and gentamicin
      (hives). The pharmacy was consulted to develop a desensitization protocol for
      ceftaroline. The desensitization protocol used three serial dilutions of
      ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular
      epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as
      needed for the development of immediate hypersensitivity reactions during or
      after administration of ceftaroline. The cumulative dose (574.94 mg) was
      administered intravenously over 225 minutes with no breakthrough symptoms
      reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg
      i.v. every 12 hours was continued for six weeks. CONCLUSION: Desensitization to
      ceftaroline was conducted for a patient with extensive history of
      hypersensitivity reactions to other drugs, including penicillin-induced
      anaphylaxis. Desensitization and subsequent treatment with full doses of
      ceftaroline were accomplished without apparent adverse effects.

PMID- 25596604
TI  - Development of an inpatient operational pharmacy productivity model.
AB  - PURPOSE: An innovative model for measuring the operational productivity of
      medication order management in inpatient settings is described. METHODS: Order
      verification within a computerized prescriber order-entry system was chosen as
      the pharmacy workload driver. To account for inherent variability in the tasks
      involved in processing different types of orders, pharmaceutical products were
      grouped by class, and each class was assigned a time standard, or "medication
      complexity weight" reflecting the intensity of pharmacist and technician
      activities (verification of drug indication, verification of appropriate dosing,
      adverse-event prevention and monitoring, medication preparation, product
      checking, product delivery, returns processing, nurse/provider education, and
      problem-order resolution). The resulting "weighted verifications" (WV) model
      allows productivity monitoring by job function (pharmacist versus technician) to
      guide hiring and staffing decisions. A 9-month historical sample of verified
      medication orders was analyzed using the WV model, and the calculations were
      compared with values derived from two established models-one based on the Case
      Mix Index (CMI) and the other based on the proprietary Pharmacy Intensity Score
      (PIS). RESULTS: Evaluation of Pearson correlation coefficients indicated that
      values calculated using the WV model were highly correlated with those derived
      from the CMI-and PIS-based models (r = 0.845 and 0.886, respectively). Relative
      to the comparator models, the WV model offered the advantage of less period-to
      period variability. CONCLUSION: The WV model yielded productivity data that
      correlated closely with values calculated using two validated workload management
      models. The model may be used as an alternative measure of pharmacy operational
      productivity.

PMID- 25596605
TI  - Impact of incorporating pharmacy claims data into electronic medication
      reconciliation.
AB  - PURPOSE: The potential value of adding pharmacy claims data to the medication
      history in the electronic health record (EHR) to improve the accuracy of
      medication reconciliation was studied. METHODS: Three medication history sources
      were used for this evaluation: a gold-standard preadmission medication list
      (PAML) created by reviewing all available medication history information, an EHR
      generated PAML, and pharmacy claims data. The study population consisted of
      patients from the Partners Medication Reconciliation Study with medication
      history information available from all three medication history sources. The
      aggregated medication list from each medication history source was compared with
      the gold-standard PAML to identify and categorize missing medications, additional
      medications, and discrepancies in the various attributes of a medication order,
      including dose, route, and frequency. McNemar's test was used to compare paired
      proportions of medication entries across each source to the gold-standard PAMLs.
      RESULTS: Fifteen patients had medication histories in all three medication
      history sources. Medication entries across all three sources included 169 from
      the gold- standard PAMLs, 158 from the EHR-PAMLs, and 351 from pharmacy claims
      data. The EHR-PAMLs and pharmacy claims data correctly reflected 52.1% and 43.2%
      of the gold-standard PAMLs, respectively. Combining the EHR-PAMLs and pharmacy
      claims resulted in 69.2% of the gold-standard PAMLs correctly reflected (p <
      0.0001). Combining these two data sources increased the accuracy of medication
      history by 17.1%. CONCLUSION: Combining the EHR-PAML and pharmacy claims data
      resulted in a significant increase in the number of medications correctly
      reflected in the gold-standard PAML compared with the EHR-PAML or claims data
      separately.

PMID- 25596606
TI  - Applying lean principles to continuous renal replacement therapy processes.
AB  - PURPOSE: The application of lean principles to continuous renal replacement
      therapy (CRRT) processes in an academic medical center is described. SUMMARY: A
      manual audit over six consecutive weeks revealed that 133 5-L bags of CRRT
      solution were discarded after being dispensed from pharmacy but before clinical
      use. Lean principles were used to examine the workflow for CRRT preparation and
      develop and implement an intervention. An educational program was developed to
      encourage and enhance direct communication between nursing and pharmacy about
      changes in a patient's condition or CRRT order. It was through this education
      program that the reordering workflow shifted from nurses to pharmacy technicians.
      The primary outcome was the number of CRRT solution bags delivered in the
      preintervention and postintervention periods. Nurses and pharmacy technicians
      were surveyed to determine their satisfaction with the workflow change. After
      implementation of lean principles, the mean number of CRRT solution bags
      dispensed per day of CRRT decreased substantially. Respondents' overall
      satisfaction with the CRRT solution preparation process increased during the
      postintervention period, and the satisfaction scores for each individual
      component of the workflow after implementation of lean principles. The decreased
      solution waste resulted in projected annual cost savings exceeding $70,000 in
      product alone. CONCLUSION: The use of lean principles to identify medication
      waste in the CRRT workflow and implementation of an intervention to shift the
      workload from intensive care unit nurses to pharmacy technicians led to reduced
      CRRT solution waste, improved efficiency of CRRT workflow, and increased
      satisfaction among staff.

PMID- 25596608
TI  - Hospital Readmissions Reduction Program: implications for pharmacy.

PMID- 25596607
TI  - Major publications in the critical care pharmacotherapy literature: January
      December 2013.
AB  - PURPOSE: Ten recently published articles with important implications for critical
      care pharmacotherapy are summarized. SUMMARY: The Critical Care Pharmacotherapy
      Literature Update (CCPLU) group is a national assembly of experienced intensive
      care unit (ICU) pharmacists across the United States. Group members monitor 25
      peer-reviewed journals on an ongoing basis to identify literature relevant to
      pharmacy practice in the critical care setting. After evaluation by CCPLU group
      members, selected articles are chosen for summarization and distribution to group
      members nationwide based on (1) applicability to critical care practice, (2)
      relevance to pharmacy practitioners, and (3) quality of evidence or research
      methodology. Hundreds of relevant articles were evaluated by the group during the
      period January-December 2013, of which 98 were summarized and disseminated
      nationally to CCPLU group members. Among those 98 publications, 10 deemed to be
      of particularly high utility to critical care practitioners were included in this
      review. The 10 articles address topics such as rapid lowering of blood pressure
      in patients with intracranial hemorrhage, adjunctive therapy to prevent renal
      injury due to acute heart failure, triple-drug therapy to improve neurologic
      outcomes after cardiac arrest, and continuous versus intermittent infusion of
      beta-lactam antibiotics in severe sepsis. CONCLUSION: There were many important
      additions to the critical care pharmacotherapy literature in 2013, including an
      updated guideline on the management of myocardial infarction and reports on
      advances in research focused on improving outcomes in patients with stroke or
      cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.

PMID- 25596613
TI  - A unique sex chromosome system in the knifefish Gymnotus bahianus with inferences
      about chromosomal evolution of Gymnotidae.
AB  - Cytogenetic studies in Neotropical electric knifefish of genus Gymnotus have
      shown a remarkable interspecific variability, including distinct sex chromosome
      systems. In this study, we present the first chromosomal data in Gymnotus
      bahianus from Contas River basin, northeastern South America. Based on extensive
      analyses, the modal diploid values were 2n = 36 (30m/sm + 6st) for females and 2n
      = 37 (32m/sm + 5st) for males. Therefore, a novel XX/XY1Y2 sex chromosome system
      is described for the genus. Single nucleolar organizer regions (NORs)
      interspersed to GC-rich sites were detected on a subtelocentric pair (7th) for
      both sexes and confirmed by fluorescent in situ hybridization with 18S rDNA
      probes. Heterochromatin was detected at pericentromeric regions of all
      chromosomes and interspersed to NORs on pair 7 and 5S rDNA cistrons on pair 9.
      The highly differentiated karyotype of Gymnoytus bahianus, with low diploid
      numbers and a unique XX/XY1Y2 system, reinforces the independent origin of sex
      chromosomes in Gymnotiformes and seems to reflect the particular evolutionary
      history of this species in a small and isolated drainage system. Moreover, in
      spite of morphological similarities, the present results indicate a remarkable
      chromosomal divergence in relation to closely related species such as G. sylvius
      and G. carapo. 

PMID- 25596612
TI  - Genetic architecture of a hormonal response to gene knockdown in honey bees.
AB  - Variation in endocrine signaling is proposed to underlie the evolution and
      regulation of social life histories, but the genetic architecture of endocrine
      signaling is still poorly understood. An excellent example of a hormonally
      influenced set of social traits is found in the honey bee (Apis mellifera): a
      dynamic and mutually suppressive relationship between juvenile hormone (JH) and
      the yolk precursor protein vitellogenin (Vg) regulates behavioral maturation and
      foraging of workers. Several other traits cosegregate with these behavioral
      phenotypes, comprising the pollen hoarding syndrome (PHS) one of the best
      described animal behavioral syndromes. Genotype differences in responsiveness of
      JH to Vg are a potential mechanistic basis for the PHS. Here, we reduced Vg
      expression via RNA interference in progeny from a backcross between 2 selected
      lines of honey bees that differ in JH responsiveness to Vg reduction and measured
      JH response and ovary size, which represents another key aspect of the PHS.
      Genetic mapping based on restriction site-associated DNA tag sequencing
      identified suggestive quantitative trait loci (QTL) for ovary size and JH
      responsiveness. We confirmed genetic effects on both traits near many QTL that
      had been identified previously for their effect on various PHS traits. Thus, our
      results support a role for endocrine control of complex traits at a genetic
      level. Furthermore, this first example of a genetic map of a hormonal response to
      gene knockdown in a social insect helps to refine the genetic understanding of
      complex behaviors and the physiology that may underlie behavioral control in
      general. 

PMID- 25596614
TI  - Fresh osteochondral allograft transplantation for isolated patellar cartilage
      injury.
AB  - BACKGROUND: The treatment of patellofemoral cartilage injuries can be
      challenging. Osteochondral allograft (OCA) transplantation has been used as a
      treatment option for a range of cartilage disorders. PURPOSE: To evaluate
      functional outcomes and survivorship of the grafts among patients who underwent
      OCA for patellar cartilage injuries. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: An institutional review board-approved OCA database was
      used to identify 27 patients (28 knees) who underwent isolated OCA
      transplantation of the patella between 1983 and 2010. All patients had a minimum
      2-year follow-up. The mean age of the patients was 33.7 years (range, 14-64
      years); 54% were female. Twenty-six (92.9%) knees had previous surgery (mean, 3.2
      procedures; range, 1-10 procedures). The mean allograft area was 10.1 cm(2)
      (range, 4.0-18.0 cm(2)). Patients returned for clinical evaluation or were
      contacted via telephone for follow-up. The number and type of reoperations were
      assessed. Any reoperation resulting in removal of the allograft was considered a
      failure of the OCA transplantation. Patients were evaluated pre- and
      postoperatively using the modified Merle d'Aubigne-Postel (18-point) scale, the
      International Knee Documentation Committee (IKDC) pain, function, and total
      scores, and the Knee Society function (KS-F) score. Patient satisfaction was
      assessed at latest follow-up. RESULTS: Seventeen of the 28 knees (60.7%) had
      further surgery after the OCA transplantation; 8 of the 28 knees (28.6%) were
      considered OCA failures (4 conversions to total knee arthroplasty, 2 conversions
      to patellofemoral knee arthroplasty, 1 revision OCA, 1 patellectomy). Patellar
      allografting survivorship was 78.1% at 5 and 10 years and 55.8% at 15 years.
      Among the 20 knees (71.4%) with grafts in situ, the mean follow-up duration was
      9.7 years (range, 1.8-30.1 years). Pain and function improved from the
      preoperative visit to latest follow-up, and 89% of patients were extremely
      satisfied or satisfied with the results of the OCA transplantation. CONCLUSION:
      OCA transplantation was successful as a salvage treatment procedure for cartilage
      injuries of the patella.

PMID- 25596615
TI  - A prospective study of injury patterns in collegiate pole vaulters.
AB  - BACKGROUND: Although pole vaulting has been a sanctioned collegiate event since
      the 1920s, little is known about the injury patterns observed in the sport.
      PURPOSE: To describe injury incidence, patterns, and risks in collegiate pole
      vaulters. STUDY DESIGN: Descriptive epidemiology study. METHODS: This was a
      prospective cohort study of collegiate athletes participating in pole vault over
      a single track-and-field season. Baseline athlete information was collected on
      study enrollment. Injuries were recorded in a standardized form to document
      diagnosis and event circumstances. A log of practice and competition exposures
      was maintained for each athlete. Injury incidence was reported as the proportion
      of injured vaulters and number of new injuries per 1000 athlete-exposures.
      Regression analysis on baseline variables was performed to determine risks for
      injury. RESULTS: A total of 135 vaulters from 15 universities took part in the
      study. There were 70 injury events reported during 8823 exposures. Forty-one
      percent of vaulters sustained injury, and there were 7.9 injuries per 1000
      athlete-exposures. The low back was the most common injury location (16.7%),
      followed by the hamstrings and lower leg (13.9% each). Overall, 60% of injuries
      were to the lower extremities, 21% to the upper extremities, and 18% to the back.
      No head or neck injuries were reported. Injuries were most commonly muscular
      strains (39.2%) or overuse type (25.5%). Thirty percent, including 83% of low
      back injuries, occurred during the plant/takeoff phase of the vault. One-third of
      lumbar injuries were spondylolysis, with 75% of these being season ending. The
      odds of injury were 2.7 (95% CI, 1.1-7.1) times greater in vaulters with multiple
      prior injuries. CONCLUSION: This is the first prospective study of injury
      patterns in collegiate pole vaulters. The results indicate that injuries are very
      common in experienced vaulters. Medical personnel and coaches should be aware of
      the propensity for overuse-type injuries and institute activity modification to
      reduce time lost. In addition, coaches and athletes should focus on proper
      technique, particularly during the plant/takeoff to help minimize back injury.
      Medical providers should maintain a high level of suspicion for symptomatic
      spondylolysis in any vaulter complaining of frequent or persistent low back pain.
      Detailed medical histories are important to identify prior injuries, and coaches
      should focus on changing technical flaws or behaviors that may contribute to
      reinjury.

PMID- 25596616
TI  - Association between ball-handling versus defending actions and acute noncontact
      lower extremity injuries in high school basketball and soccer.
AB  - BACKGROUND: High school-sponsored athletic programs currently provide more than
      7.7 million students in the United States with health and societal benefits, but
      they also inherently increase the risk of students sustaining a sports injury.
      Understanding risk factors that predict injuries in sports is an essential first
      step to addressing the problem in this population. PURPOSE: To determine the role
      of offensive versus defensive actions in noncontact lower extremity injury rates
      in high school basketball and soccer in both boys' and girls' sports. STUDY
      DESIGN: Descriptive epidemiological study. METHODS: Noncontact lower extremity
      injury data were collected from academic years 2005-2006 through 2011-2012 for
      boys' and girls' basketball and soccer through the surveillance tool High School
      RIO (reporting information online). The injuries in this subset of the database
      occurred over a total of 6.4 million athlete-exposures. RESULTS: Significant
      differences in overall lower extremity injury rates were found when comparing
      ball-handling and defending actions in basketball (rate ratio [RR], 1.36; 95% CI,
      1.08-1.73; P = .009), but no appreciable difference was observed in soccer (RR,
      0.89; 95% CI, 0.70-1.12; P = .31). Female participants had higher injury rates
      than did males for both ball-handling and defending actions for both sports (P <
      .05). Only girls' soccer showed significant differences in the odds ratio (OR) of
      defending to ball-handling injury rates between competition and practice (OR,
      1.88; 95% CI, 1.01-3.48; P = .047). CONCLUSION: The injury rate differences
      observed in this study between offensive and defensive actions suggest that
      investigating potential differences between sport-specific tasks may provide a
      more complete understanding of injury mechanisms.

PMID- 25596619
TI  - Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for
      gene therapy.

PMID- 25596618
TI  - Long-term outcomes in eyes receiving fixed-interval dosing of anti-vascular
      endothelial growth factor agents for wet age-related macular degeneration.
AB  - PURPOSE: To report on long-term visual outcomes in patients receiving continuous
      fixed-interval dosing of anti-vascular endothelial growth factor (VEGF) treatment
      in neovascular age-related macular degeneration (AMD). DESIGN: Single-practice
      retrospective chart review. PARTICIPANTS: One hundred nine eyes with exudative
      AMD receiving continuous fixed-interval dosing (every 4-8 weeks) of anti-VEGF
      therapy (ranibizumab, bevacizumab, or aflibercept) for at least 5 years. Eyes
      were excluded if they averaged fewer than 6.5 injections per year. METHODS:
      Snellen visual acuity was recorded at baseline and all subsequent injections.
      Changes from baseline were calculated at yearly intervals. MAIN OUTCOME MEASURES:
      The primary outcome measure was mean change in letter score at 5, 6, and 7 years;
      secondary outcomes included the percentage of patients with 20/40 vision or
      better at 7 years and the mean change in letter score at each yearly time point
      based on baseline visual grouping (20/40 or better, 20/50-20/100, 20/200 or
      worse). RESULTS: Forty-four, 75, and 109 patients with 7, 6, and 5 years,
      respectively, of continuous treatment were identified. Mean change in letter
      score at year 5 was +14.0 letters (P = 3.9 * 10(-9)), +12.2 letters at 6 years (P
      = 1.5 * 10(-7)), and +12.1 letters at 7 years (P = 3.8 * 10(-5)). Driving vision
      (20/40 or better) was achieved in 43.2% of treated eyes. Subanalysis revealed
      that the greatest visual gains at 5 and 7 years were seen in those patients with
      baseline visual acuity worse than 20/200 (+24.5 and +25.5 letters), followed by
      those with 20/50 to 20/100 vision (+6.7 and +6.9 letters), and finally those with
      20/20 to 20/40 (+3.7 and +3.4 letters). Patients received an average of 10.5
      injections per year. CONCLUSIONS: Continuous fixed-interval dosing of anti-VEGF
      therapy in patients with exudative AMD results in favorable long-term
      preservation out to 7 years, with vision stabilizing or improving in 93.2% of
      eyes. Additionally, 43.2% of patients maintained driving vision in the treatment
      eye at 7 years compared with 10.1% at baseline. Our data suggest better outcomes
      with continuous therapy over published results with sporadic, as-needed therapy.

PMID- 25596620
TI  - Bowman layer transplantation to reduce and stabilize progressive, advanced
      keratoconus.
AB  - OBJECTIVE: To evaluate the clinical outcome of mid-stromal isolated Bowman layer
      transplantation, a new surgical technique to reduce and stabilize ectasia in eyes
      with advanced keratoconus, to postpone penetrating keratoplasty or deep anterior
      lamellar keratoplasty, and to enable continued daily contact lens wear. DESIGN:
      Prospective, nonrandomized cohort study at a tertiary referral center.
      PARTICIPANTS: Twenty-two eyes of 19 patients with progressive, advanced
      keratoconus not eligible for ultraviolet cross-linking. INTERVENTIONS: The mid
      stroma was manually dissected and an isolated donor Bowman layer was positioned
      within the stromal pocket. MAIN OUTCOME MEASURES: Before and up to 36 months
      after surgery (mean follow-up, 21+/-7 months), best spectacle-corrected visual
      acuity (BSCVA), best contact lens-corrected visual acuity (BCLVA), Scheimpflug
      based corneal tomography measurements, endothelial cell density, biomicroscopy,
      refraction, and intraoperative and postoperative complications were recorded.
      RESULTS: Two surgeries were complicated by an intraoperative perforation of
      Descemet membrane; no other intraoperative or postoperative complications were
      observed. Maximum keratometry decreased on average from 77.2+/-6.2 diopters (D)
      to 69.2+/-3.7 D (P < 0.001) at 1 month after surgery and remained stable
      thereafter (P >= 0.072). Mean BSCVA improved from 1.27+/-0.44 logarithm of the
      minimum angle of resolution units before surgery to 0.90+/-0.30 logarithm of the
      minimum angle of resolution units 12 months after surgery (P < 0.001), whereas
      BCLVA remained stable (P = 0.105). Mean thinnest-point pachymetry increased from
      332+/-59 MUm before surgery to 360+/-50 MUm at the latest follow-up (P = 0.012),
      and no change in endothelial cell density was found (P = 0.355). CONCLUSIONS:
      With isolated Bowman layer transplantation, reduction and stabilization of
      corneal ectasia was achieved in eyes with progressive, advanced keratoconus.
      Given the low risk for complications, the procedure may be performed to postpone
      penetrating or deep anterior lamellar keratoplasty.

PMID- 25596621
TI  - Clinical implementation of a reactive balance control assessment in a sub-acute
      stroke patient population using a 'lean-and-release' methodology.
AB  - Reactive balance control, specifically performance of rapid stepping responses,
      is associated with falls, but not routinely assessed in clinical practice.
      Challenges to clinical assessment may include a lack of available methods that
      are safe, standardized and able to quantify the balance responses. We implemented
      a reactive balance control assessment, using lean-and-release methodology, in an
      inpatient stroke rehabilitation program. Through retrospective chart review of
      all admissions (n=183) over a 1-year period, we evaluated the clinical uptake and
      patient-specific factors associated with its use. Seventy-seven of 183 (42%)
      patients were administered the assessment, on average, 16.2 (SD 13.1) days post
      admission. Patients who received the assessment were younger, at an earlier time
      post-stroke, with a shorter rehabilitation length of stay, with less lower-limb
      impairment, higher levels of functional balance, less motor and cognitive
      impairment, greater recovery of functional mobility, and were more likely to have
      the capacity to walk (all measures p<0.0001), compared to those who did not
      receive the assessment. This study demonstrates the potential for clinical uptake
      of the lean-and-release assessment among patients with stroke, who are
      progressing in their functional and mobility status over the course of their
      inpatient rehabilitation. However, the results suggest limitations in application
      to patients with greater disability or who demonstrate slower recovery of
      functional mobility. Ongoing research is required to develop clinical approaches
      to reactive balance control assessment that are effective, efficient and relevant
      to clinical populations and feasible for clinical practice.

PMID- 25596622
TI  - Leiomyoma-derived transforming growth factor-beta impairs bone morphogenetic
      protein-2-mediated endometrial receptivity.
AB  - OBJECTIVE: To determine whether transforming growth factor (TGF)-beta3 is a
      paracrine signal secreted by leiomyoma that inhibits bone morphogenetic protein
      (BMP)-mediated endometrial receptivity and decidualization. DESIGN: Experimental.
      SETTING: Laboratory. PATIENT(S): Women with symptomatic leiomyomas.
      INTERVENTION(S): Endometrial stromal cells (ESCs) and leiomyoma cells were
      isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied
      to cultured ESC. The TGF-beta was blocked by two approaches: TGF-beta pan
      specific antibody or transfection with a mutant TGF-beta receptor type II. Cells
      were then treated with recombinant human BMP-2 to assess BMP responsiveness. MAIN
      OUTCOME MEASURE(S): Expression of BMP receptor types 1A, 1B, 2, as well as
      endometrial receptivity mediators HOXA10 and leukemia inhibitory factor (LIF).
      RESULT(S): Enzyme-linked immunosorbent assay showed elevated TGF-beta levels in
      LCM. LCM treatment of ESC reduced expression of BMP receptor types 1B and 2 to
      approximately 60% of pretreatment levels. Preincubation of LCM with TGF-beta
      neutralizing antibody or mutant TGF receptor, but not respective controls,
      prevented repression of BMP receptors. HOXA10 and LIF expression was repressed in
      recombinant human BMP-2 treated, LCM exposed ESC. Pretreatment of LCM with TGF
      beta antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF
      repression. CONCLUSION(S): Leiomyoma-derived TGF-beta was necessary and
      sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-beta
      prevents repression of BMP-2 receptors and restores BMP-2-stimulated expression
      of HOXA10 and LIF. Blockade of TGF signaling is a potential strategy to improve
      infertility and pregnancy loss associated with uterine leiomyoma.

PMID- 25596625
TI  - Factors associated with the duration of untreated illness among patients with
      obsessive compulsive disorder.
AB  - BACKGROUND: Patients suffering from obsessive compulsive disorder (OCD), despite
      heightened levels of functional impairment and disability, often wait several
      years before starting pharmacological treatment. The interval between the onset
      of a specific psychiatric disorder and administration of the first
      pharmacological treatment has been conceptualized as the duration of untreated
      illness (DUI). The DUI has been increasingly investigated as a predictor of long
      term outcomes for OCD and other anxiety disorders. The present study investigated
      DUI, and demographic-clinical factors associated with DUI, among a sample of
      patients with OCD. The relationships between DUI, insight, and treatment outcomes
      were also assessed. METHODS: We evaluated 96 subjects with a DSM-IV diagnosis of
      OCD using the Structured Clinical Interview for DSM-IV Axis I disorders, a
      semistructured interview for sociodemographic and clinical features, the Yale
      Brown Obsessive-Compulsive Scale (Y-BOCS), and a questionnaire designed by our
      group to identify reasons for delaying psychiatric admission. Patients with OCD
      showed a mean DUI of 84 months. However, DUI was not predictive of remission
      defined by a Y-BOCS total score of 10. Using the median value, a categorical cut
      off for DUI of 4 years was calculated. RESULTS: For patients with a shorter DUI
      (<=4 years), the age of OCD onset was significantly older than patients with a
      longer DUI (>4 years) (p<.001). The following four items related to reasons for
      delaying treatment were significantly endorsed by patients: the fact that
      symptoms were spontaneously fluctuating over time (61.5%), believing that OCD
      symptoms were not associated with an illness (60.4%), believing that one can
      overcome symptoms by him/herself (55.2%), and not being significantly disturbed
      by OCD symptoms (33.3%). Delaying treatment because of perceived social stigma
      was only endorsed by 12.5% of patients. Believing that OCD symptoms were not
      associated with an illness was significantly associated with a longer DUI
      (p=.039). CONCLUSIONS: Results from the present study suggest that patients with
      OCD show a significant inclination toward delaying treatment admission. However,
      DUI was not predictive of remission in terms of symptomatology. Believing that
      OCD symptoms are not associated with an illness might indicate impairment in
      insight, a denial of the problem or could be associated with awareness of OCD as
      a mental illness. Factors related to the nature and course of OCD appear to be
      important determinants in delaying treatment among patients with OCD.

PMID- 25596626
TI  - Tumor necrosis factor-alpha and interleukin-17 differently affects Langerhans
      cell distribution and activation in an innovative three-dimensional model of
      normal human skin.
AB  - Among the several cytokines involved in the psoriasis pathogenesis, tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-17 play a central role. Many
      biomolecular steps remain unknown due to difficulty to obtain psoriatic models.
      To investigate the effect of TNF-alpha and IL-17 on the ultrastructure,
      immunophenotype, and number of epidermal Langerhans cells (LCs), human skin
      explants (n=7) were cultured air-liquid interface in a Transwell system. Four
      different conditions were used: medium alone (control), medium added with 100
      ng/ml TNF-alpha or 50 ng/ml IL-17 or a combination of both cytokines. Samples
      were harvested 24 and 48 h after cytokine addition and were frozen. Samples
      harvested at 24h were also processed for transmission electron microscopy (TEM).
      By immunofluorescence analysis with anti-human Langerin antibody (three
      experiments/sample) we calculated the percentage of LCs/mm(2) of living epidermis
      after 24 and 48 h of incubation (considering control as 100%). At 24h LC number
      was significantly higher in samples treated with both cytokines (216.71+15.10%;
      p<0.001) and in TNF-alpha (125.74+26.24%; p<0.05). No differences were observed
      in IL-17-treated samples (100.14+38.42%). After 48 h, the number of epidermal
      Langerin-positive cells in IL-17- and TNF-alpha treated samples slightly
      decreased (94.99+36.79% and 101.37+23% vs. their controls, respectively). With
      the combination of both cytokines epidermal LCs strongly decreased (120+13.36%).
      By TEM, upon TNF-alpha stimulus LCs appeared with few organelles, mostly
      mitochondria, lysosomes, and scattered peripherical BGs. Upon IL-17 stimulus, LCs
      showed a cytoplasm with many mitochondria and numerous BGs close to the
      perinuclear space and Golgi apparatus, but also at the periphery, at the
      beginning of the dendrites. The addition of both cytokines did not affect LC
      ultrastructure. Our study showed that IL-17 induced significant changes in LC
      ultrastructure, while the combination of both cytokines seems to have a strong
      chemo-attractant effect on epidermal LCs, supporting the relevance of
      investigating the interplay between LCs and pro-inflammatory cytokines in the
      ongoing of the disease.

PMID- 25596624
TI  - Problems in sexual functioning among male OEF/OIF veterans seeking treatment for
      posttraumatic stress.
AB  - OBJECTIVE: Few studies have examined sexual dysfunction among Operations
      Enduring/Iraqi Freedom (OEF/OIF) veterans with posttraumatic stress disorder
      (PTSD). The present study investigated predictors of erectile dysfunction [ED]
      and self-reported sexual problems among 150 male combat veterans seeking
      outpatient treatment for PTSD within the Veterans Affairs healthcare system.
      METHOD: Participants completed clinical interviews and several questionnaires
      including measures of sexual arousal and sexual desire. A medical records review
      was also conducted to document evidence of an ED diagnosis or associated
      medication use. RESULTS: An ED diagnosis was present for 12% of the sample, and
      10% were taking associated medications. Sexual arousal problems were reported by
      sixty-two percent of partnered veterans. Sexual desire problems were endorsed by
      63% of the total sample, and by 72% of partnered veterans. Age was the only
      significant predictor of ED diagnosis or medication use. Age, race, PTSD
      diagnosis (versus subclinical symptoms), depression, and social support predicted
      self-reported sexual arousal problems; while race, combat exposure, social
      support, and avoidance/numbing symptoms of PTSD predicted self-reported sexual
      desire problems. CONCLUSIONS: Sexual problems are common among male OEF/OIF
      combat veterans seeking treatment for PTSD. Moreover, avoidance/numbing symptoms
      robustly predicted sexual desire problems. These findings highlight the
      importance of expanding assessment of sexual dysfunction and support the need for
      additional research in this area.

PMID- 25596623
TI  - Achieving sustained virologic response in hepatitis C: a systematic review of the
      clinical, economic and quality of life benefits.
AB  - BACKGROUND: The goal of chronic hepatitis C treatment is to remove the virus to
      avoid progression of HCV-related disease. Sustained virologic response (SVR) is
      the most widely used efficacy endpoint in clinical studies of hepatitis C, and
      represents the eradication of HCV from the body. The aim of the current review
      was to examine the long-term clinical, economic and quality of life benefits
      associated with achieving SVR. METHODS: A systematic literature review was
      performed using the PubMed, EMBASE and Cochrane library databases to identify
      articles examining the clinical, economic and quality of life benefits associated
      with SVR, published in English language from 2002-2013. For inclusion studies
      were required to enroll >=100 patients and to report clinical endpoints including
      hepatocellular carcinoma, overall- or liver-related mortality, or progression of
      disease/complications (e.g. portal hypertension, esophageal varices). Review of
      economic studies on cost/cost-effectiveness of achieving SVR were focused on
      studies assessing boceprevir/telaprevir plus pegIFN and ribavirin as this
      represents the current standard of care in several jurisdictions worldwide.
      Quality of life evidence was required to use validated quality of life
      instruments and provide a quantitative analysis of the impact of SVR versus no
      treatment or treatment failure. RESULTS: SVR is durable with late relapse rates
      over 4-5 year periods being in the range of 1-2%. Patients who achieve SVR
      frequently demonstrate some regression of fibrosis/cirrhosis and have a
      substantially reduced risk for hepatocellular carcinoma (relative risk [RR] 0.1
      0.25), liver-related mortality (RR 0.03-0.2) and overall mortality (RR 0.1-0.3)
      in comparison with no treatment or treatment failure. In the 5 years post
      treatment, medical costs for patients achieving SVR are 13-fold lower than
      patients not achieving SVR. Patients who achieve SVR also have health state
      utility values that are 0.05 to 0.31 higher than non-responders to treatment.
      CONCLUSIONS: SVR represents the fundamental goal of antiviral treatment for
      patients infected with chronic HCV, so as to reduce risk of liver disease
      progression. Achievement of SVR has implications beyond those of clearing viral
      infection; it is associated with improved long-term clinical outcomes, economic
      benefits and improved health-related quality of life.

PMID- 25596628
TI  - In vitro evidence of the structural optimization of the human skeletal bones.
AB  - Optimization can be seen in a number of human skeletal bones. While there is
      strong evidence concerning the mechanism at the tissue-level for bone adaptation
      to the applied loads, the structural optimization at the organ-level is somewhat
      less clear. This paper reviews the evidence, mainly based on in vitro testing,
      but also from anatomical and biomechanical considerations, concerning the shape
      function relationship in some exemplar cases. The proximal femur is robustly
      optimized to resist a force applied in a range of directions during daily life,
      but also to absorb a large amount of energy if an impact is delivered on the
      greater trochanter during a sideways fall. The diaphysis of the tibia is shaped
      so as to act as a uniform-stress structure (i.e. structurally efficient) when
      loaded by a bending moment in the sagittal plane, such as during locomotion. The
      body of the thoraco-lumbar vertebrae is optimized to resist to a load applied
      strictly in an axial direction. The result of this review suggests that the
      structure of bones derives from a combination of local stimulus-driven tissue
      level adaptation within the subject, and organ-level generational evolution. 

PMID- 25596627
TI  - Acute respiratory distress syndrome and outcomes after near hanging.
AB  - PURPOSE: The purpose of this study is to assess the case rate of acute
      respiratory distress syndrome (ARDS) after near hanging and the secondary
      outcomes of traumatic and/or anoxic brain injury and death. Risk factors for the
      outcomes were assessed. METHOD: The method is a single-center, statewide
      retrospective cohort study of consecutive patients admitted between August 2002
      and September 2011, with a primary diagnosis of nonjudicial "hanging injury."
      RESULTS: Of 56 patients, 73% were male. The median age was 31 (Interquartile
      range (IQR), 16-56). Upon arrival, 9% (5/56) did not have a pulse, and 23%
      (13/56) patients were intubated. The median Glasgow Coma Scale (GCS) was 13 (IQR,
      3-15); 14% (8/56) had a GCS = 3. Acute respiratory distress syndrome developed in
      9% (5/56) of patients. Traumatic anoxic brain injury resulted in 9% (5/56) of
      patients. The in-hospital case fatality was 5% (3/56). Lower median GCS (3 [IQR,
      3-7] vs 14 [IQR, 3-15]; P = .0003) and intubation in field or in trauma
      resuscitation unit (100% [5/5] vs 16% [8/51]; P = .0003) were associated with
      ARDS development. Risk factors of death were GCS = 3 (100% [3/3] vs 9% [5/53]; P
      = .002), pulselessness upon arrival of emergency medical services (100% [3/3] vs
      4% [2/53]; P < .001], and abnormal neurologic imaging (50% [1/2] vs zero; P =
      .04). CONCLUSIONS: The ARDS case rate after near hanging is similar to the
      general trauma population. Low GCS and intubation are associated with increased
      risk of ARDS development. The rate of traumatic and/or anoxic brain injury in
      this population is low.

PMID- 25596630
TI  - Mechanical characterization of stomach tissue under uniaxial tensile action.
AB  - In this article, the tensile properties of gastric wall were investigated by
      using biomechanical test and theoretical analysis. The samples of porcine stomach
      strips from smaller and greater curvature of the stomach were cut in longitudinal
      and circumferential direction, respectively. The loading-unloading, stress
      relaxation, strain creep, tensile fracture tests were performed at mucosa
      submucosa, serosa-muscle and intact layer, respectively. Results showed that the
      biomechanical properties of the porcine stomach depended on the layers,
      orientations and locations of the gastric wall and presented typical
      viscoelastic, nonlinear and anisotropic mechanical properties. During loading
      unloading test, the stress of serosa-muscle layer in the longitudinal direction
      was 15-20% more than that in the circumferential direction at 12% stretch ratio,
      while it could reach about 40% for the intact layer and 50% for the mucosa
      submucosa layer. The results of stress relaxation and strain creep showed that
      the variation degree was obviously faster in the circumferential direction than
      that in the longitudinal direction, and the ultimate residual values were also
      different for the different layers, orientations and locations. In the process of
      fracture test, the serosa-muscle layer fractured firstly followed by the mucosa
      submucosa layer when the intact layer was tested, the longitudinal strips firstly
      began to fracture and the required stress value was about twice as much as that
      in the circumferential strips. The anisotropy and heterogeneity of mechanical
      characterization of the porcine stomach were related to its complicated geometry,
      structure and functions. The results would help us to understand the biomechanics
      of soft organ tissue.

PMID- 25596629
TI  - Age-related changes in dynamic compressive properties of trochanteric soft
      tissues over the hip.
AB  - Hip fracture risk increases dramatically with age, and 90% of fractures are due
      to falls. During a fall on the hip, the soft tissues overlying the hip region
      (skin, fat, and muscle) act as shock absorbers to absorb energy and reduce the
      peak force applied to the underlying bone. We conducted dynamic indentation
      experiments with young women (aged 19-30; n=17) and older women (aged 65-81;
      n=17) to test the hypothesis that changes occur with age in the stiffness and
      damping properties of these tissues. Tissue stiffness and damping were derived
      from experiments where subjects lay sideways on a bed with the greater trochanter
      contacting a 3.8cm diameter indenter, which applied sinusoidal compression
      between 5 to 30Hz with a peak-to-peak amplitude of 1mm. Soft tissue thickness was
      measured using ultrasound. On average, stiffness was 2.9-fold smaller in older
      than young women (5.7 versus 16.8kN/m, p=0.0005) and damping was 3.5-fold smaller
      in older than young women (81 versus 282Ns/m, p=0.001). Neither parameter
      associated with soft tissue thickness. Our results indicate substantial age
      related reductions in the stiffness and damping of soft tissues over the hip
      region, which likely reduce their capacity to absorb and dissipate energy (before
      "bottoming out") during a fall. Strategies such as wearable hip protectors or
      compliant flooringmay compensate for age-related reductions in the shock
      absorbing properties of soft tissues and decrease the injury potential of falls.

PMID- 25596631
TI  - Intracellular forces during guided cell growth on micropatterns using FRET
      measurement.
AB  - Interaction of cells with extracellular matrix (ECM) regulates cell shape,
      differentiation and polarity. This effect has been widely observed in cells grown
      on substrates with various patterned features, stiffness and surface chemistry.
      It has been postulated that mechanical confinement of cells by the substrate
      causes a redistribution of tension in cytoskeletal proteins resulting in
      cytoskeletal reorganization through force sensitive pathways. However, the
      mechanisms for force transduction during reorganization remain unclear. In this
      study, using FRET based force sensors we have measured tension in an actin cross
      linking protein, alpha-actinin, and followed reorganization of actin cytoskeleton
      in real time in HEK cells grown on patterned substrates. We show that the
      patterned substrates cause a redistribution of tension in alpha-actinin that
      coincides with cytoskeleton reorganization. Higher tension was observed in
      portions of cells where they form bridges across inhibited regions of the
      patterned substrates; the attachment to the substrate is found to release
      tension. Real time measurements of alpha-actinin tension and F-actin arrangement
      show that an increase in tension coincides with formation of F-actin bundles at
      the cell periphery during cell-spreading across inhibited regions, suggesting
      that mechanical forces stimulate cytoskeleton enhancement. Rho-ROCK inhibitor
      (Y27632) causes reduction in actinin tension followed by retraction of bridged
      regions. Our results demonstrate that changes in cell shape and expansion over
      patterned surfaces is a force sensitive process that requires actomyosin
      contractile force involving Rho-ROCK pathway.

PMID- 25596632
TI  - Effect of partially demineralized dentin beneath the hybrid layer on dentin
      adhesive interface micromechanics.
AB  - OBJECTIVE: To investigate the presence of non-infiltrated, partially
      demineralized dentin (PDD) beneath the hybrid layer for self-etch adhesive
      systems, and its effect on micromechanical behavior of dentin-adhesive interfaces
      (DAIs). This in-vitro laboratory and computer simulation study hypothesized that
      the presence of non-infiltrated PDD beneath the hybrid layer does not influence
      the mechanical behavior of the DAI of self-etch adhesive systems. METHODS:
      Fifteen sound third molars were restored with composite resin using three
      adhesive systems: Scotchbond Multipurpose (SBMP), Clearfil SE Bond (CSEB) and
      Adper Promp L-Pop (APLP). The thickness and length of all DAIs were assessed
      using scanning electron microscopy, and used to generate three-dimensional finite
      element models. Elastic moduli of the hybrid layer, adhesive layer, intertubular
      dentin, peritubular dentin and resin tags were acquired using a nano-indenter.
      Finite element software was used to determine the maximum principal stress. Mixed
      models analysis of variance was used to verify statistical differences (P<0.05).
      RESULTS: Elastic moduli and morphology were found to differ between the adhesive
      systems, as well as the presence and extension of PDD. SIGNIFICANCE: Both self
      etch adhesive systems (APLP and CSEB) had PDD. The DAI stress levels were higher
      for the one-step self-etch adhesive system (APLP) compared with the etch-and
      rinse adhesive system (SBMP) and the self-etch primer system (CSEB).

PMID- 25596633
TI  - Digit mechanics in relation to endpoint compliance during precision pinch.
AB  - This study investigates the mechanics of the thumb and index finger in relation
      to compliant endpoint forces during precision pinch. The objective was to gain
      insight into how individuals modulate motor output at the digit endpoints and
      joints according to compliance-related sensory feedback across the digits.
      Thirteen able-bodied subjects performed precision pinch upon elastic resistance
      bands of a customized apparatus instrumented with six degree-of-freedom load
      cells. Compliance levels were discretely adjusted according to the number of
      bands connected. Subjects were provided visual feedback to control the rate of
      force application. Fifteen repetitions of low-to-moderate force (<20N) pinches
      were analyzed at each of five compliance levels, during which force and motion
      data were collected. Joint angles and moments normalized by pinch force magnitude
      were computed. Second-order polynomials were used to characterize joint mechanics
      as a function of compliance. The joint degrees-of-freedom (DOFs) at the finger
      showed greater dependence on compliance for angular position while the thumb
      joint DOFs demonstrated greater dependence for normalized joint moment. The
      digits also adjusted coordination of their endpoint forces according to
      compliance. Overall, the finger may be altering its position to increase load to
      the joints of the thumb with changing compliance. These findings describe
      naturally emergent changes in digit mechanics for compliant precision pinch,
      which involves motor execution in response to endpoint sensory feedback.
      Identifying and understanding these motor patterns may provide theoretical basis
      for restoring and rehabilitating sensorimotor pathologies of the hand.

PMID- 25596634
TI  - Computational modelling of left-ventricular diastolic mechanics: effect of fibre
      orientation and right-ventricle topology.
AB  - Majority of heart failure patients who suffer from diastolic dysfunction retain
      normal systolic pump action. The dysfunction remodels the myocardial fibre
      structure of left-ventricle (LV), changing its regular diastolic behaviour.
      Existing LV diastolic models ignored the effects of right-ventricular (RV)
      deformation, resulting in inaccurate strain analysis of LV wall during diastole.
      This paper, for the first time, proposes a numerical approach to investigate the
      effect of fibre-angle distribution and RV deformation on LV diastolic mechanics.
      A finite element modelling of LV passive inflation was carried out, using
      structure-based orthotropic constitutive law. Rule-based fibre architecture was
      assigned on a bi-ventricular (BV) geometry constructed from non-invasive imaging
      of human heart. The effect of RV deformation on LV diastolic mechanics was
      investigated by comparing the results predicted by BV and single LV model
      constructed from the same image data. Results indicated an important influence of
      RV deformation which led to additional LV passive inflation and increase of
      average fibre and sheet stress-strain in LV wall during diastole. Sensitivity of
      LV passive mechanics to the changes in the fibre distribution was also examined.
      The study revealed that LV diastolic volume increased when fibres were aligned
      more towards LV longitudinal axis. Changes in fibre angle distribution
      significantly altered fibre stress-strain distribution of LV wall. The simulation
      results strongly suggest that patient-specific fibre structure and RV deformation
      play very important roles in LV diastolic mechanics and should be accounted for
      in computational modelling for improved understanding of the LV mechanics under
      normal and pathological conditions.

PMID- 25596635
TI  - Development of a computational framework to adjust the pre-impact spine posture
      of a whole-body model based on cadaver tests data.
AB  - A method was developed to adjust the posture of a human numerical model to match
      the pre-impact posture of a human subject. The method involves pulling cables to
      prescribe the position and orientation of the head, spine and pelvis during a
      simulation. Six postured models matching the pre-impact posture measured on
      subjects tested in previous studies were created from a human numerical model.
      Posture scalars were measured on pre- and after applying the method to evaluate
      its efficiency. The lateral leaning angle thetaL defined between T1 and the
      pelvis in the coronal plane was found to be significantly improved after
      application with an average difference of 0.1+/-0.1 degrees  with the PMHS (4.6+/
      2.7 degrees  before application). This method will be applied in further studies
      to analyze independently the contribution of pre-impact posture on impact
      response using human numerical models.

PMID- 25596637
TI  - The use of Doppler evaluation of the canine umbilical artery in prediction of
      delivery time and fetal distress.
AB  - The aim of this study was to describe changes in umbilical artery blood flow in
      the later stages of canine pregnancy. Seventeen pregnant bitches were examined
      sonographically to evaluate umbilical artery blood flow at the following
      antepartum times: 120-96, 96-72, 72-48, 48-24, 24-12, 12-6 and 6-1h. The peak
      systolic velocity and end diastolic velocity were measured to calculate the
      resistive index (RI). Bitches were classified into two groups according to
      delivery method: normal delivery (Group 1, n=11) and Cesarean section, due to
      fetal distress, (Group 2, n=6). During the study, the RI of the umbilical artery
      in bitches in Group 1 significantly declined in the time periods 72-48, 24-12, 12
      6 and 6-1h before delivery when compared to the reference RI (120-96h antepartum
      period), with values below 0.7 in the 12-6 and 6-1h periods. In Group 2, the RI
      decreased significantly in the antepartum periods 96-72, 72-48, 48-24h with
      respect to the period 120-96h, and increased in the periods from 24-12, 12-6 and
      6-1h (being significantly higher in this last period) until the time of Cesarean
      section. Therefore monitoring of changes in umbilical artery RI in the pre-partum
      period may provide information about time of delivery in bitches and also assist
      in the diagnosis of possible dystocia and fetal distress. 

PMID- 25596636
TI  - Urinary phthalate metabolites in relation to maternal serum thyroid and sex
      hormone levels during pregnancy: a longitudinal analysis.
AB  - BACKGROUND: Increasing scientific evidence suggests that exposure to phthalates
      during pregnancy may be associated with an elevated risk of adverse reproductive
      outcomes such as preterm birth. Maternal endocrine disruption across pregnancy
      may be one pathway mediating some of these relationships. We investigated whether
      urinary phthalate metabolites were associated with maternal serum thyroid (free
      thyroxine [FT4], free triiodothyronine [FT3], and thyroid-stimulating hormone
      [TSH]), and sex (estradiol, progesterone, and sex hormone-binding globulin
      [SHBG]) hormone levels at multiple time points during pregnancy. METHODS:
      Preliminary data (n = 106) were obtained from an ongoing prospective birth cohort
      in Northern Puerto Rico. We collected urine and serum sample at the first and
      third study visits that occurred at 18 +/- 2 and 26 +/- 2 weeks of gestation,
      respectively. To explore the longitudinal relationships between urinary phthalate
      metabolites and serum thyroid and sex hormone concentrations, we used linear
      mixed models (LMMs) adjusted for prepregnancy body mass index (BMI) and maternal
      age. An interaction term was added to each LMM to test whether the effect of
      urinary phthalate metabolites on serum thyroid and sex hormone levels varied by
      study visit. In cross-sectional analyses, we stratified BMI- and age-adjusted
      linear regression models by study visit. RESULTS: In adjusted LMMs, we observed
      significant inverse associations between mono-3-carboxypropyl phthalate (MCPP)
      and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross
      sectional analyses by study visit, we detected stronger and statistically
      significant inverse associations at the third study visit between FT3 and MCPP as
      well as mono-carboxyisooctyl phthalate (MCOP); also at the third study visit,
      significant inverse associations were observed between FT4 and metabolites of di
      (2-ethylhexyl) phthalate (DEHP). The inverse association between MEP and
      progesterone was consistent across study visits. CONCLUSIONS: In this group of
      pregnant women, urinary phthalate metabolites may be associated with altered
      maternal serum thyroid and sex hormone levels, and the magnitude of these effects
      may depend on the timing of exposure during gestation.

PMID- 25596639
TI  - Development of a novel miniplex DNA identification system for the Japanese
      population.
AB  - To aid DNA identification using 36 short tandem repeat (STR) loci for kinship
      analysis, likelihood ratio (LR) distributions were estimated using the allele
      frequency data evaluated for the Japanese population in our previous study. The
      results revealed that the LR tended to be higher when kinship analysis was
      performed using the 36 STR loci than when the analysis was performed using
      Identifiler(r), the most commonly used commercial DNA typing kit in Japan, even
      when a sibship case was analyzed. However, a typing kit targeting 36 STR loci is
      not suitable for the analysis of damaged DNA. In this study, we developed a novel
      miniplex DNA identification system targeting 7 STR loci (D3S1744, D5S818,
      D8S1179, D10S2325, Penta D, Penta E, and vWA) that was optimized for use in
      combination with MiniFilerTM for the Japanese population. The combined matching
      probability of the MiniFiler plus miniplex system was 4.8*10(-19), which is lower
      than that of Identifiler (4.3*10(-17)). All expected alleles were detected
      successfully on DNA isolated from HepG2 human hepatocarcinoma cells by the
      miniplex system, but no significant signal was observed from a DNA sample
      isolated from COS-7 African green monkey kidney cells. 

PMID- 25596638
TI  - The role of dentin matrix protein 1 (DMP1) in regulation of osteogenic
      differentiation of rat dental follicle stem cells (DFSCs).
AB  - OBJECTIVES: Primary isolated dental follicle stem cells (DFSCs) possess a strong
      osteogenesis capability, and such capability is reduced during in vitro culture.
      Because dentin matrix protein 1 (DMP1) is essential in the maturation of
      osteoblasts, our objectives were to determine (1) the expression of DMP1 in the
      DFSCs, (2) the correlation between DMP1 expression and osteogenic capability of
      DFSCs, and (3) the ability of DMP1 to promote osteogenic differentiation of
      DFSCs. METHODS: DFSCs and their non-stem cell counterpart dental follicle cells
      (DFC) were established from postnatal rat pups. Expression of DMP1 in the DFSCs
      and DFC was determined using real-time RT-PCR and western blotting. Different
      passages of DFSCs were subjected to osteogenic induction. The correlation between
      osteogenesis and DMP1 expression was analyzed. Then, expression of DMP1 in the
      DFSCs was knocked-down using siRNA, followed by osteogenic induction to evaluate
      the effect of DMP1-knockdown. Finally, the late passage DFSCs with reduced DMP1
      expression and osteogenic capability were cultured in osteogenic induction medium
      containing mouse recombinant DMP1 (mrDMP1) to determine if DMP1 can restore
      osteogenesis of DFSCs. RESULTS: DFSCs expressed much higher levels of DMP1 than
      did DFC. DMP1 expression was correlated with the osteogenic capability of DFSCs.
      Knockdown of DMP1 expression markedly decreased the osteogenesis and osteogenic
      gene expression in the DFSCs whereas adding mrDMP1 protein to the osteogenic
      induction medium enhanced osteogenesis. CONCLUSIONS: DMP1 is highly expressed in
      the DFSCs, but minimally expressed in non-stem cell DFC. DMP1 appears to play an
      important role for osteogenic differentiation of the DFSCs.

PMID- 25596640
TI  - Accuracy of subthalamic nucleus targeting by T2, FLAIR and SWI-3-Tesla MRI
      confirmed by microelectrode recordings.
AB  - BACKGROUND: Successful deep brain stimulation is mostly dependent on accurate
      positioning of the leads at the optimal target points. We investigated whether
      the identification of the subthalamic nucleus in T2-weighted 3-T MRI, fluid
      attenuated inversion recovery 3-T MRI and susceptibility-weighted 3-T MRI is
      confirmed by intraoperative neurological microelectrode recording. METHODS: We
      evaluated 182 microelectrode recording leads in 21 patients with bilateral deep
      brain stimulation, retrospectively. Consequently, 728 electrode contact positions
      in T2-weighted 3-T MRI, 552 electrode contact positions in fluid-attenuated
      inversion recovery 3-T MRI and 490 electrode contact positions in susceptibility
      weighted 3-T MRI were evaluated for a positive nucleus subthalamicus signal.
      RESULTS: The highest sensitivity was measured for fluid-attenuated inversion
      recovery 3-T MRI with 82.5 %, while the highest specificity was observed for
      susceptibility-weighted 3-T MRI with 90.6 %. The negative predictive value was
      nearly equal for susceptibility-weighted MRI and fluid-attenuated inversion
      recovery MRI with 87.5 % vs. 87.1 %, but the positive predictive value was higher
      in susceptibility-weighted 3-T MRI (86.0 %) than in the other MRI sequences.
      CONCLUSIONS: The susceptibility-weighted 3-T MRI-based subthalamic nucleus
      localization shows the best accuracy compared with T2-weighted and fluid
      attenuated inversion recovery 3-T MRI. Therefore, the susceptibility-weighted 3-T
      MRI should be preferred for surgical planning when the operation procedure is
      performed under general anesthesia without microelectrode recordings.

PMID- 25596642
TI  - Erratum to: Gamma Knife, CyberKnife or micro-multileaf collimator LINAC for
      intracranial radiosurgery?

PMID- 25596641
TI  - Fully endoscopic retrosigmoid approach for posterior petrous meningioma and
      trigeminal microvascular decompression.
AB  - BACKGROUND: Cerebellopontine angle tumor resection and cranial nerve
      microvascular decompression are usually performed with the aid of the surgical
      microscope. The endoscope is commonly used as an adjuvant. METHOD: A retrosigmoid
      craniectomy is done. Upon dural opening, the endoscope is inserted into the
      operative field along the petrotentorial junction. Cerebrospinal fluid drainage
      provides a wider space for introduction of the endoscope and surgical
      instruments. Traditional microsurgical techniques are used during the entire
      procedure. CONCLUSION: A fully endoscopic retrosigmoid approach is a safe and
      effective procedure for cerebellopontine angle tumor resection and cranial nerve
      microvascular decompression. KEY POINTS: * Careful examination of preoperative
      studies is needed to identify anatomical peculiarities. * Patient positioning:
      the head must be gently flexed and its vertex gently tilted toward the floor. *
      Neurophysiologic monitoring and intraoperative navigation. * Craniectomy: partial
      exposure of the transverse and sigmoid sinuses. * Curvilinear dural incision
      reflected laterally to minimize the risk of sinus injury. * Opening the
      cerebellomedullary cistern for CSF drainage and cerebellar relaxation. * Dynamic
      endoscopy enhances depth perception and must be performed by a team with
      experience in endoscopic intracranial surgery. * Traditional microsurgical
      techniques have to be applied during the entire operation. * Multilayer
      reconstruction, including watertight dural closure. * Meningiomas causing
      brainstem shift are not suitable for endoscopic resection.

PMID- 25596643
TI  - [Multiple intracranial arteriovenous malformation].
AB  - Multiple cerebral arteriovenous malformations (AVMs) are thought to be
      exceedingly rare lesions and have usually been reported as single cases. The
      incidence of multiple cerebral AVMs in major series ranges from 0.3% to 9% and,
      in the majority of cases, these malformations are associated with other vascular
      anomalies of the brain or soft tissues. We report a 62-year-old woman that
      presented with a left temporal haemorrhage. Angiography showed 3 AVMs located in
      the left temporal lobe, left cerebellar hemisphere and right temporal lobe. The
      lesions were treated with radiosurgery. 

PMID- 25596644
TI  - Chemotherapy and novel therapeutics before radical prostatectomy for high-risk
      clinically localized prostate cancer.
AB  - Although both surgery and radiation are potential curative options for men with
      clinically localized prostate cancer, a significant proportion of men with high
      risk and locally advanced disease will demonstrate biochemical and potentially
      clinical progression of their disease. Neoadjuvant systemic therapy before
      radical prostatectomy (RP) is a logical strategy to improve treatment outcomes
      for men with clinically localized high-risk prostate cancer. Furthermore,
      delivery of chemotherapy and other systemic agents before RP affords an
      opportunity to explore the efficacy of these agents with pathologic end points.
      Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen
      deprivation therapy), has demonstrated feasibility and safety in men undergoing
      RP, but no study to date has established the efficacy of neoadjuvant chemotherapy
      or neoadjuvant chemohormonal therapies. Other novel agents, such as those
      targeting the vascular endothelial growth factor receptor, epidermal growth
      factor receptor, platelet-derived growth factor receptor, clusterin, and
      immunomodulatory therapeutics, are currently under investigation. 

PMID- 25596645
TI  - Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph
      node metastases of urothelial cancer of the bladder.
AB  - PURPOSE: To assess whether Bcl-2, an inhibitor of the apoptotic cascade, can
      predict response to neoadjuvant chemotherapy in patients with urothelial cancer
      of the bladder (UCB). METHODS: Bcl-2 expression was analyzed in 2 different
      tissue microarrays (TMAs). One TMA was constructed of primary tumors and their
      corresponding lymph node (LN) metastases from 152 patients with chemotherapy
      naive UCB treated by cystectomy and pelvic lymphadenectomy (chemotherapy-naive
      TMA cohort). The other TMA was constructed of tumor samples obtained from 55
      patients with UCB before neoadjuvant chemotherapy (transurethral resection of the
      bladder cancer) and after cystectomy with pelvic lymphadenectomy (residual
      primary tumor [ypT+], n = 38); residual LN metastases [ypN+], n = 24)
      (prechemotherapy/postchemotherapy TMA cohort). Bcl-2 overexpression was defined
      as 10% or more cancer cells showing cytoplasmic immunoreactivity. RESULTS: In
      both TMA cohorts, Bcl-2 overexpression was significantly (P<0.05) more frequent
      in LN metastases than in primary tumors (chemotherapy-naive TMA group: 18/148
      [12%] in primary tumors vs. 39/143 [27%] in metastases; postchemotherapy TMA:
      ypT+7/35 [20%] vs. ypN+11/19 [58%]). In the neoadjuvant setting, patients with
      Bcl-2 overexpression in transurethral resection of the bladder cancer specimens
      showed significantly (P = 0.04) higher ypT stages and less regression in their
      cystectomy specimens than did the control group, and only one-eighth (13%) had
      complete tumor regression (ypT0 ypN0). In survival analyses, only
      histopathological parameters added significant prognostic information.
      CONCLUSIONS: Bcl-2 overexpression in chemotherapy-naive primary bladder cancer is
      related to poor chemotherapy response and might help to select likely
      nonresponders.

PMID- 25596648
TI  - Evaluation of hearing loss in pediatric celiac patients.
AB  - OBJECTIVES: Celiac disease (CD) is a chronic immune-mediated enteropathy caused
      by the ingestion of gluten in genetically predisposed individuals. In some
      reports, sensorineural hearing loss (SNHL) has been identified as an
      extraintestinal symptom of CD. We aimed to further investigate the possible
      association between CD and SNHL by examining a greater number of pediatric CD
      patients. METHODS: The study was carried out from March to September 2014 and
      included 110 pediatric patients with biopsy-confirmed CD (220 ears) and 41 age-
      and sex-matched controls (82 ears); participants were evaluated by tympanometry
      and pure tone audiometry (frequency, 250-8000Hz frequency). RESULTS: Audiometric
      bone conduction thresholds were significantly different between the CD patients
      and the controls (p<0.05), but there were no significant differences in pure tone
      averages for air conduction (p>0.05). When the results for CD patients were
      analyzed according to duration of disease (<=36 months and >36 months), a
      significant difference in bone conduction thresholds (p<0.05) was noted, with
      significant increments at the later stages of disease. However, this difference
      was not sufficient to define clinical hearing loss, as the pure tone average
      thresholds remained below 20dB. CONCLUSION: These results indicate that
      subclinical hearing loss may be present in children with CD, which could presage
      more serious hearing impairments at older ages and later stages of the disease.
      Hearing screenings should be recommended for children with CD in order to prevent
      the potentially unfavorable effects of hearing loss on the emotional, behavioral,
      cognitive, and sensorimotor development of these patients.

PMID- 25596647
TI  - Risk factors for otitis media effusion in children who have adenoid hypertrophia.
AB  - OBJECTIVE: Many studies have shown that children with adenoid hypertrophy (AH)
      are more likely to have chronic otitis media with effusion (COME). However, not
      every child with AH has COME. In this study, we investigated the socio
      demographic risk factors of children who underwent surgery for AH, including a
      subgroup with COME. Our aim was to identify the factors involved in the
      development of COME. METHODS: The study population consisted of 170 pediatric
      patients (118 males, 52 females) who underwent adenoidectomy between 2005 and
      2008. The patients were divided into two groups, those with AH alone and those
      with AH and COME (AH+COME). Major factors such as age, gender, breast-milk
      feeding, bottle-feeding, tobacco smoke exposure, familial predisposition,
      allergies, congenital diseases, and school attendance were compared between the
      two groups. RESULTS: AH alone was detected in 102 of the patients, 68% of whom
      were male, and AH+COME in the remaining 68, of whom 72% were male. The mean age
      was 6.5 years in the AH group and 5.3 years in the AH+COME group. There were no
      significant differences between the two groups with respect to breast-feeding,
      bottle-feeding, familial predisposition, tobacco exposure, and allergies.
      However, the relationships between COME and male sex, congenital diseases, and
      school attendance were significant. CONCLUSIONS: COME is seen in young children
      with AH. Among the socio-demographic features examined in this study, only male
      sex, congenital diseases, and school attendance were statistically significant
      risk factors for COME development.

PMID- 25596649
TI  - Histopathological evaluation of Ankaferd blood stopper use in the rabbit
      septoplasty model.
AB  - OBJECTIVE: The purpose of this study was to assess the use of Ankaferd blood
      stopper (ABS), an organic hemostatic agent of plant origin, in septoplasty
      operations, and to determine its effect on nasal septal tissues in the rabbit
      model. METHOD: The study was performed on 30 New Zealand adult male rabbits each
      weighing 2500-3500g (average: 3000g). The rabbits were randomly divided into 4
      groups, namely, the control group (without septoplasty), the septoplasty+tampon
      group, the septoplasty+ABS group, and the septoplasty+tampon+ABS group. All
      animals were sacrificed after two weeks, and the nasal septums were total removed
      using the lateral rhinotomy technique. The specimens were obtained from similar
      sites of cartilaginous nasal septum. The sections were stained with hematoxylin
      eosin and Mason trichrome stains and studied under the light microscope by the
      same pathologist who evaluated the mucosal ulcerations, the severity of
      inflammatory cell infiltration, the mucosal thickness, and the cartilage
      thickness. The data obtained were statistically analyzed using the Kruskal-Wallis
      variance analysis and the Mann-Whitney U test. RESULTS: No mucosal ulceration or
      inflammatory cell infiltration was detected in any of the rabbit groups. There
      was a statistically significant difference between the groups in terms of mucosal
      thickness and cartilage thickness (p<0.05). The values of mucosal thickness in
      the groups mentioned above were 147.7+/-17.6MUm, 205.7+/-36.7MUm, 139.6+/
      14.8MUm, and 190.2+/-17.5MUm, respectively. The values of cartilage thickness
      were 398.2+/-28.9MUm, 546.2+/-35.3MUm, 363.7+/-24.7MUm, and 447.8+/-28.2MUm,
      respectively. There was no significant difference between the control group and
      the septoplasty+ABS group in terms of mucosal thickness and cartilage thickness
      (p>0.05). However, there was a significant increase in nasal mucosal and
      cartilage thickness in tampon-using groups when compared with the other groups
      (p<0.05). CONCLUSION: Although nasal tampons provide the contact of
      mucoperichondrium with the cartilage, they are generally accepted as a discomfort
      for patients. Ankaferd blood stopper can be used instead of nasal tampons to
      increase patient comfort.

PMID- 25596646
TI  - CD55 deposited on synovial collagen fibers protects from immune complex-mediated
      arthritis.
AB  - INTRODUCTION: CD55, a glycosylphosphatidylinositol-anchored, complement
      regulating protein (decay-accelerating factor), is expressed by fibroblast-like
      synoviocytes (FLS) with high local abundance in the intimal lining layer. We here
      explored the basis and consequences of this uncommon presence. METHODS: Synovial
      tissue, primary FLS cultures, and three-dimensional FLS micromasses were
      analyzed. CD55 expression was assessed by quantitative polymerase chain reaction
      (PCR), in situ hybridization, flow cytometry, and immunohistochemistry. Reticular
      fibers were visualized by Gomori staining and colocalization of CD55 with
      extracellular matrix (ECM) proteins by confocal microscopy. Membrane-bound CD55
      was released from synovial tissue with phospholipase C. Functional consequences
      of CD55 expression were studied in the K/BxN serum transfer model of arthritis
      using mice that in addition to CD55 also lack FcgammaRIIB (CD32), increasing
      susceptibility for immune complex-mediated pathology. RESULTS: Abundant CD55
      expression seen in FLS of the intimal lining layer was associated with linearly
      oriented reticular fibers and was resistant to phospholipase C treatment.
      Expression of CD55 colocalized with collagen type I and III as well as with
      complement C3. A comparable distribution of CD55 was established in three
      dimensional micromasses after >=3 weeks of culture together with the ECM. CD55
      deficiency did not enhance K/BxN serum-induced arthritis, but further exaggerated
      disease activity in Fcgr2b (-/-) mice. CONCLUSIONS: CD55 is produced by FLS and
      deposited on the local collagen fiber meshwork, where it protects the synovial
      tissue against immune complex-mediated arthritis.

PMID- 25596650
TI  - Quality indicators in a newborn hearing screening service.
AB  - INTRODUCTION: Newborn hearing screening (NHS) programs are implemented across the
      globe to detect early hearing impairment. In order to meet this objective, the
      quality of these programs should be monitored using internationally recognized
      indicators. OBJECTIVE: To evaluate a newborn hearing screening service (NHSS)
      using international quality indicators. METHODS: A retrospective cohort study on
      the NHSS of Minas Gerais was conducted, analyzing the services performed between
      2010 and 2011. Results were analyzed according to criteria from the American
      Academy of Pediatrics and the Joint Committee on Infant Hearing. RESULTS: This
      study assessed 6987 children. The proportions of cases that were referred for a
      retest, that followed through with retest, and that were referred for diagnosis
      were 8.0%, 71.9%, and 2.1%, respectively. The proportion of assessed newborn
      children in the first 30 days of life in this study was 65%. The median age of
      those children who failed both the NHS and the retest was significantly higher
      than the other children. The chance of a child with a hearing impairment risk
      indicator to fail the NHS was 2.4 times higher than of those without a risk
      indicator. CONCLUSION: NHSS achieved three of four evaluated indicators. Despite
      this, it is still necessary to perform NHS earlier and to ensure that the
      subsequent steps are followed.

PMID- 25596651
TI  - Effect of unilateral congenital cataract surgery on ocular axial length growth
      and corneal flattening.
AB  - OBJECTIVE: The aim of this article is to study the effect of unilateral
      congenital cataract surgery on ocular growth and corneal flattening. METHODS:
      This is a cross-sectional study of 59 patients operated on due to a unilateral
      congenital cataract. The median age of the patients at the time of diagnosis was
      17 months (interquartile range, 5-39 months). The median age at cataract the time
      of surgery was 28 months (interquartile range, 8-52 months), and the mean follow
      up between cataract surgery and assessments was 149.7+/-69.9 months (range, 30
      319 months). Axial length and corneal curvature were measured in both operated
      and non-operated eyes, comparing the results between them. RESULTS: There were no
      statistically significant differences for axial length growth or corneal
      flattening between operated and non-operated eyes: axial length (P=.327, Student
      t test) and corneal curvature (P=.078, Student t test). A sub-analysis was
      performed using the visual acuity and the age of the patient at the time of
      surgery. The only statistically significant data (P=.007, Student t test) was a
      lower axial length in operated eyes compared to non-operated eyes, in the non
      deep-amblyopia group. CONCLUSIONS: No significant axial length growth
      modifications were observed between operated and non-operated eyes. Only the non
      deep-amblyopia group presented with a lower axial length in the operated eyes
      compared to non-operated eyes. No significant differences in corneal flattening
      were found between groups after unilateral congenital cataract surgery.

PMID- 25596652
TI  - [Ophthalmoplegic migraine: A real eye emergency].

PMID- 25596654
TI  - Electrocatalytic Reduction of Nitrogen and Carbon Dioxide to Chemical Fuels:
      Challenges and Opportunities for a Solar Fuel Device.
AB  - Aspects of the electrochemical reduction of nitrogen and carbon dioxide at
      molecular and heterogeneous catalysts are discussed. We focus on recent advances
      in the field and touch on some of the remaining challenges in the production of
      solar fuels from N2 and CO2 with a direct, integrated solar fuel device. As such,
      we now propose metrics of catalyst assessment for non-H2 solar fuels. 

PMID- 25596653
TI  - New directions for sepsis and septic shock research.
AB  - BACKGROUND: Septic shock is a frequent complication in intensive care unit that
      can result in multiple organ failure and death. In addition, recent data
      suggested that severe sepsis and septic shock represent an economic burden.
      Therefore, septic shock is an important public health problem. METHOD: In this
      review, we will focus on the recent evidences concerning the stages of septic
      shock, the complex macrocirculation and microcirculation relationship, and the
      importance of those evidences for future resuscitation goals and therapeutic
      strategies during late septic shock. RESULT: Recently, two stages of septic shock
      are suggested. In early stage, hypovolemia is the main contributing factor.
      During this stage, macrocirculatory and microcirculatory changes run parallel,
      and fluid resuscitation seems to be effective in restoring the hemodynamic
      parameters. Late stage of septic shock is characterized by complex
      microcirculation and macrocirculation relationship. CONCLUSIONS: Although early
      goal-directed therapy is a stepwise approach in the treatment of septic shock,
      tissue perfusion remains an important factor that contributes to septic shock
      outcome. Because appropriate monitoring of tissue perfusion is a matter of debt,
      the ideal therapeutic strategy remains a controversial issue that needs further
      investigations.

PMID- 25596656
TI  - Normal reference ranges for and variability in the levels of blood manganese and
      selenium by gender, age, and race/ethnicity for general U.S. population.
AB  - Data from National Health and Nutrition Examination Survey for the period 2011
      2012 were used to determine normal reference ranges and percentile distributions
      for manganese (Mn) and selenium (Se) in blood by gender, age, race/ethnicity,
      socioeconomic status as determined by annual family income, and smoking status.
      The effect of gender, age, race/ethnicity, family income, and smoking status on
      the levels of Mn and Se was also determined by fitting regression models. Males
      had lower adjusted levels of Mn and higher adjusted levels of Se than females.
      Adjusted levels of Mn decreased with increase in age but adjusted levels of Se
      were lower in adolescents aged 12-19 years than adults aged 20-64 years. Non
      Hispanic black (NHB) had the lowest levels of both Mn and Se and non-Hispanic
      Asians (NHAS) had the highest levels of both Mn and Se. Non-Hispanic white (NHW)
      and NHB had lower levels of Mn than Hispanics (HISP) and NHAS. NHB and HISP had
      lower levels of Se than NHW and NHAS. Low annual income (<$20,000) was associated
      with lower levels of Se than high annual income (>=$55,000). Smoking negatively
      affected the adjusted levels of Se among seniors aged >=65 years but this was not
      observed in other age groups. Mn levels were not affected by smoking. 

PMID- 25596655
TI  - Phenothiazinium photoantimicrobials with basic side chains.
AB  - Derivatives of the standard cationic photosensitiser, methylene blue, were
      synthesised, having extra amino (basic) functionality in the auxochromic side
      chain. The resulting analogues were profiled for photodynamic activity in vitro,
      and screened against standard Gram-positive and Gram-negative bacteria for
      photobactericidal activity. The substitution pattern of the derivatives was such
      that ionisation of the amino groups in situ, via protonation, provided a range of
      charge distribution and degree of charge across the molecular framework. While
      most examples exhibited greater activity than the lead compound, in addition to
      similar activity to the known, but more powerful, phenothiazinium
      photoantimicrobial, dimethyl methylene blue, this was also associated with
      relatively high dark toxicity, inferring that these compounds were targeting
      crucial structures before illumination. One derivative having an asymmetrical
      structure, with separation between a lipophilic and a hydrophilic region
      exhibited a combination of very high phototoxicity coupled with very low dark
      effects, against both the standard screen and an additional one containing
      further, relevant pathogen species, including Candida albicans. It is suggested
      that the great activity of this analogue is due to efficient membrane targeting. 

PMID- 25596657
TI  - Aurora kinase A gene copy number is associated with the malignant transformation
      of colorectal adenomas but not with the serrated neoplasia progression.
AB  - A crucial role for Aurora Kinase A (AURKA) gene has been demonstrated in the
      advanced steps of colorectal tumor progression. Little is known, however, about
      its role in the early phases of the adenoma-carcinoma sequence. Moreover, no data
      are currently available concerning AURKA involvement in the serrated
      tumorigenesis. Fluorescence in situ hybridization analysis and
      immunohistochemistry were used to assess gene copy number and protein expression
      in 40 colorectal adenomas, 20 cancerized adenomas, and 20 serrated polyps. An
      increased copy number was found either in adenomatous tissue or in early cancer
      in the vast majority of cancerized adenomas, but only in 5% of adenomas (P <
      .001). Protein expression strictly paralleled fluorescence in situ hybridization
      results. No changes in the gene copy number were observed in serrated polyps,
      regardless of their histotype and the presence of dysplasia, even if high
      percentages of immunostained cells were detected in all the subgroups. AURKA gene
      is associated with progressive colorectal adenomas but is uninvolved in the
      development of nonprogressive adenomas. The diploid status of the gene is
      maintained along the progression of serrated neoplasia. AURKA protein expression
      in serrated polyps is uncoupled from gene status and is likely to reflect
      apoptotic dysregulation. 

PMID- 25596658
TI  - EGFR-based bioradiotherapy in SCCHN.

PMID- 25596659
TI  - Panitumumab plus radiotherapy versus chemoradiotherapy in patients with
      unresected, locally advanced squamous-cell carcinoma of the head and neck
      (CONCERT-2): a randomised, controlled, open-label phase 2 trial.
AB  - BACKGROUND: We aimed to compare panitumumab, a fully human monoclonal antibody
      against EGFR, plus radiotherapy with chemoradiotherapy in patients with
      unresected, locally advanced squamous-cell carcinoma of the head and neck.
      METHODS: In this international, open-label, randomised, controlled, phase 2
      trial, we recruited patients with locally advanced squamous-cell carcinoma of the
      head and neck from 22 sites in eight countries worldwide. Patients aged 18 years
      and older with stage III, IVa, or IVb, previously untreated, measurable (>= 10 mm
      for at least one dimension), locally advanced squamous-cell carcinoma of the head
      and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group
      performance status of 0-1 were randomly assigned (2:3) by an independent vendor
      to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during
      radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9
      mg/kg every 3 weeks administered with radiotherapy) using a stratified
      randomisation with a block size of five. All patients received 70-72 Gy to gross
      tumour and 54 Gy to areas of subclinical disease with accelerated fractionation
      radiotherapy. The primary endpoint was local-regional control at 2 years,
      analysed in all randomly assigned patients who received at least one dose of
      their assigned protocol-specific treatment (chemotherapy, radiation, or
      panitumumab). The trial is closed and this is the final analysis. This study is
      registered with ClinicalTrials.gov, number NCT00547157. FINDINGS: Between Nov 30,
      2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment
      (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab
      group). Local-regional control at 2 years was 61% (95% CI 47-72) in the
      chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab
      group. The most frequent grade 3-4 adverse events were mucosal inflammation (25
      [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in
      the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and
      radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were
      reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30
      (34%) of 89 patients in the radiotherapy plus panitumumab group. INTERPRETATION:
      Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy
      for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and
      the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the
      head and neck needs to be reassessed. FUNDING: Amgen.

PMID- 25596660
TI  - Chemoradiotherapy with or without panitumumab in patients with unresected,
      locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a
      randomised, controlled, open-label phase 2 trial.
AB  - BACKGROUND: Panitumumab is a fully human monoclonal antibody that targets EGFR.
      We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy
      alone in patients with unresected, locally advanced squamous-cell carcinoma of
      the head and neck. METHODS: In this international, open-label, randomised,
      controlled, phase 2 trial, we recruited patients with locally advanced squamous
      cell carcinoma of the head and neck from 41 sites in nine countries worldwide.
      Patients aged 18 years and older with stage III, IVa, or IVb, previously
      untreated, measurable (>= 10 mm for at least one dimension), locally advanced
      squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern
      Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3)
      by an independent vendor to open-label chemoradiotherapy (three cycles of
      cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of
      intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using
      stratified randomisation with a block size of five. All patients received 70 Gy
      to gross tumour and 50 Gy to areas at risk for subclinical disease with standard
      fractionation. The primary endpoint was local-regional control at 2 years,
      analysed in all randomised patients who received at least one dose of their
      assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab).
      The trial is closed and this is the final analysis. This trial is registered with
      ClinicalTrials.gov, number NCT00500760. FINDINGS: Between Oct 26, 2007, and March
      26, 2009, 153 patients were enrolled and 150 received treatment (63 in the
      chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group).
      Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy
      group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most
      frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the
      chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus
      chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and
      radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were
      reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37
      (43%) of 87 patients in the panitumumab plus chemoradiotherapy group.
      INTERPRETATION: In patients with locally advanced squamous-cell carcinoma of the
      head and neck, the addition of panitumumab to standard fractionation radiotherapy
      and cisplatin did not confer any benefit, and the role of EGFR inhibition in
      these patients needs to be reassessed. FUNDING: Amgen.

PMID- 25596661
TI  - Premature ovarian insufficiency: from pathogenesis to clinical management.
AB  - Premature ovarian insufficiency (POI) represents a condition characterized by the
      absence of normal ovarian function due to an incipient (by 3-10 years) ovarian
      aging. In most of the women affected there are no signs or symptoms that precede
      the interruption of menstruation and the onset of POI and the majority of women
      have a normal history of menarche, regular menstrual cycles and normal fertility.
      The possible genetic role in the development of POI has been largely demonstrated
      and many genes have been involved; on the other hand, ovary is not protected
      immunologically and the detection of autoantibodies directed against various
      ovarian targets strongly support the hypothesis of an autoimmune etiology. In
      approximately 5-10% of women with a diagnosis of POI with a normal karyotype, a
      spontaneous pregnancy could occur even if the recovery of ovarian function is
      temporary and poorly predictable. Embryo donation and adoption are other
      alternatives that should be considered. POI and subsequent loss of reproductive
      capacity is a devastating condition and a difficult diagnosis for women to accept
      so it requires an individualized and a multidisciplinary approach. Hormonal
      replacement therapy (HRT) should be commenced as soon as possible to prevent and
      to contrast the onset of the symptoms related to hypoestrogenism and to improve
      the quality of life for these women.

PMID- 25596662
TI  - Calcium-phosphate metabolism in patients with multiple sclerosis.
AB  - INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate the
      concentration of 25-hydroxycholecalciferol and parameters of calcium-phosphate
      metabolism at different periods of relapsing-remitting multiple sclerosis (RRMS).
      MATERIALS AND METHODS: Forty-five patients, residents of Poland (49 degrees -50
      degrees , N), were enrolled in the study, i.e. 15 immediately after the diagnosis
      of RRMS, 15 at the early stage and 15 at the advanced stage of RRMS. The results
      were compared to values obtained in 20 age- and sex-matched controls. RESULTS:
      Lower serum concentrations of 25-hydroxycholecalciferol and ionised calcium were
      found in patients compared to the control group. In patients with the disease
      duration of 5-6 years, concentrations of 25-hydroxycholecalciferol and ionised
      calcium were lower than in patients in the earlier period of RRMS. The inverse
      and clearer direction of changes was found in parathormone serum concentration in
      patients compared to the controls. In patients with a longer disease duration, a
      significantly lower 25-hydroxycholecalciferol concentration was found in female
      patients compared to male patients. In patients, more frequent 25
      hydroxycholecalciferol and unsaturated fatty acids' supplementation was observed
      compared to the controls. CONCLUSIONS: In RRMS patients, calcium-phosphate
      metabolism is disturbed which increases during disease progression.

PMID- 25596663
TI  - Alexithymia, more than depression, influences glycaemic control of type 2
      diabetic patients.
AB  - PURPOSE: Psychiatric disorders could affect the patients' abilities to cope with
      diabetes. The objectives of this study were to assess the prevalence of
      depression and alexithymia among type 2 diabetic patients and investigate the
      possible correlations between these psychopathological phenomena and glycaemic
      control assessed through glycated hemoglobin (HbA1c). METHODS: All the patients
      were evaluated through 20-item Toronto Alexithymia Scale (TAS-20), Hamilton
      rating scale for depression and Quality of Life Index. HbA1c values, diabetes
      duration, therapy and socio-demographic characteristics were recorded. RESULTS:
      One hundred and twenty-eight patients (75 males and 53 female, mean age 64.7 +/-
      11.2 years) were enrolled. Alexithymic patients, compared to non-alexithymic
      ones, presented a significantly higher HbA1c (7.7 +/- 1.5 vs. 7 +/- 1.5, p =
      0.016). No statistically significant difference was found when comparing the
      HbA1c of depressed versus non-depressed patients. Considering the raw values of
      HbA1c, the higher percentage was recorded among patients suffering from
      depression plus alexithymia (comorbidity group) followed by patients presenting
      alexithymia only, patients with neither depression nor alexithymia (control
      group) and, finally, those presenting depression only. The comorbidity group
      presented a significantly higher value of HbA1c (7.7 +/- 1.2) than the control
      group (7 +/- 1.6, p < 0.04) and the depressed patients (6.9 +/- 1.3, p = 0.04).
      At the logistic regression, the HbA1c was found to be significantly associated
      only with alexithymia (TAS-20 total score) and insulin therapy. CONCLUSIONS:
      Alexithymia more than depression influences glycaemic control. When evaluating a
      diabetic patient, a rapid screening for psychopathological alterations would
      guarantee a more accurate management. The treatment of any associated psychiatric
      disorders would improve the patients' quality of life.

PMID- 25596665
TI  - Limited impact of drug exposure misclassification from non-benefit
      thiazolidinedione drug use on mortality and hospitalizations from Saskatchewan,
      Canada: a cohort study.
AB  - PURPOSE: Our purpose was to measure the effect of non-benefit drug use on
      observed associations between exposure and outcome, thereby documenting an
      empirical example of the potential magnitude of biases introduced when exposure
      status is misclassified from a restrictive drug coverage policy. METHODS: New
      users of antidiabetic agents were identified with a 1-year washout period between
      January 1, 1995, and December 31, 2005, in Saskatchewan, Canada, and were
      followed until December 31, 2008. Within this population-based cohort, persons
      were classified as users of benefit or non-benefit thiazolidinediones (TZDs)
      according to their first prescription record between January 1, 2006, and
      December 31, 2006 (non-benefit prescription records were not captured before
      2006). An intention-to-treat approach was used to categorize TZD exposure over
      time. We evaluated the potential bias introduced by drug exposure
      misclassification by evaluating bootstrapped differences in hazard ratio (HR)
      estimates of all-cause hospitalization or death between users and nonusers of
      TZDs obtained from analyses that contained complete drug use (non-benefit and
      benefit drug use) versus benefit drug use only (non-benefit drug use was
      misclassified as unexposed). All analyses were replicated within the same cohort
      of new users of antidiabetic agents for clopidogrel and beta-blocker (bisoprolol
      or carvedilol) users versus nonusers because these agents were also subject to
      exposure misclassification from non-benefit drug use during the period of the
      study. FINDINGS: Among 27,333 new users of antidiabetic agents, we identified
      5759 TZD users (28% non-benefit) and 21,574 nonusers of TZDs. The crude HR for
      hospitalization or death among TZD users versus nonusers was higher in a database
      that contained benefit-only prescriptions than in a database that contained all
      prescriptions (HR = 1.11 [95% CI, 1.05-1.18] vs HR = 0.99 [95% CI, 0.94-1.04]).
      However, the differences in HRs after adjustment for demographic characteristics,
      health care utilization, comorbidities, and medications suggested minimal bias
      was introduced when TZD exposure was misclassified in the benefit-only database
      (adjusted HR [aHR] = 1.04 [95% CI. 0.98-1.10] vs aHR = 0.99 [95% CI, 0.94-1.04];
      bootstrapped aHR difference = +0.05 [95% CI, 0.02-0.08]). Minimal differences in
      aHRs were also observed within analyses of clopidogrel (1551 users [24% non
      benefit]; bootstrapped aHR difference = +0.01 [95% CI, -0.04 to 0.06]) and beta
      blocker users (351 users [42% non-benefit]; bootstrapped aHR difference = +0.06
      [95% CI, -0.09 to 0.20]) versus nonusers. IMPLICATIONS: Although patient
      characteristics and outcomes differed between users of non-benefit and benefit
      drugs, misclassification of drug exposure did not meaningfully bias estimates of
      all-cause mortality and hospitalization after covariate adjustment in our study.

PMID- 25596664
TI  - Long-term outcome of Graves' orbitopathy following high-dose intravenous
      glucocorticoids and orbital radiotherapy.
AB  - OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) and orbital radiotherapy
      (ORT) are commonly used in active Graves' orbitopathy (GO), with favorable
      outcomes in up to 80% of patients. However, little is known on the factors that
      may affect GO outcome in the long term, an issue that we investigated here.
      METHODS: We studied retrospectively 96 untreated patients with GO, identified out
      of 787 consecutive patients who came to our GO Clinic for a follow-up visit
      between September 2010 and June 2013. After the first observation, patients were
      treated with ivGC and ORT and were then re-examined after a median period of 55.5
      months. The primary end-point was the possible relation between GO outcome and
      several individual variables. RESULTS: Exophthalmometry, eyelid aperture, CAS,
      diplopia and visual acuity (the latter only in patients with an initial
      reduction) improved significantly after treatment. Overall, 67.7% of patients had
      improved and were considered as responders, whereas the remaining (29.1% stable
      and 4.5% worsened) were considered as non-responders. Age, smoking, thyroid
      volume, thyroid treatment, serum anti-TSH receptor autoantibodies and individual
      GO features at first observation did not affect the outcome of GO, which, in
      contrast, was affected by gender and by the time elapsed between first and last
      observation. Thus, the prevalence of responders was higher in females (76.4 vs
      48% in males, P = 0.02) and the time elapsed between first and last observation
      was greater in responders (58 vs 39 months in non-responders, P = 0.02). Whereas
      the prevalence of responders and non-responders was similar up to 36 months,
      there was an increase in responders beginning between 37 and 48 months and
      reaching a peak of ~80% between 61 and 72 months, to plateau thereafter.
      CONCLUSIONS: Given the limitations of retrospective investigations, our study
      confirms that the combination of GC and ORT is effective in GO and shows that
      females have greater chances to respond to treatment. The notorious tendency of
      GO to improve spontaneously with time most likely contributes the long-term
      outcome of the eye syndrome.

PMID- 25596667
TI  - Minimally invasive oesophagectomy in Wales.
AB  - INTRODUCTION: The uptake of minimally invasive oesophagectomy remains low in the
      UK. As the only centre in Wales which offers this approach, our aim was to
      determine the short-term outcomes following endoscopic 2-stage oesophagectomy
      with stapled intra-thoracic anastomosis. METHODS: Details of 50 consecutive
      patients [88% (44) male, median age (range) 66 (42-83) years] with operable mid
      to distal oesophageal and gastro-oesophageal junctional cancer who underwent
      endoscopic 2-stage oesophagectomy were analysed prospectively between June 2009
      to November 2013. Primary outcome measures were overall and disease free survival
      from diagnosis. Secondary outcome measures were length of hospital stay,
      morbidity, mortality, lymph node harvest and margin involvement. RESULTS: Median
      follow-up was 25 months. Seventy per cent (n = 35) of patients had stage II or
      greater disease and underwent neoadjuvant chemotherapy. The median length of
      hospital stay was 10 (range 8-104) days. There was a trend towards a decreasing
      length of stay as experience increased. Overall 30-day operative morbidity was
      40% (n = 20) and there was no 30, 60, 90-day or in-patient mortality. Anastomotic
      leak occurred in 6 patients (12%). The median lymph node harvest was 20 (range 7
      35) nodes. Nine patients (18%) had involvement of the circumferential resection
      margin (all T3). Overall and disease free 2-year survival was 84.2 and 80.9%
      respectively. CONCLUSIONS: Endoscopic 2-stage oesophagectomy can be performed
      safely and effectively with good early oncological and surgical outcomes.

PMID- 25596666
TI  - HIF-alpha Promotes Chronic Myelogenous Leukemia Cell Proliferation by
      Upregulating p21 Expression.
AB  - We sought to determine the expression levels of hypoxia-inducible factor-1alpha
      (HIF-1alpha) in the bone marrow chronic myelogenous leukemia (CML) patients. We
      also tried to determine the roles HIF-1alpha in the proliferation of CML cells by
      small interfering RNA (siRNA) knockdown. Real-time PCR was performed to determine
      the expression levels of HIF-1alpha in the bone marrows of CML patients and
      healthy volunteers. HIF-1alpha knockdown by siRNA in K562 cells was confirmed by
      RT-PCR. Proliferation and colony formation of the treated cells were determined
      by CCK8 after HIF-1alpha knockdown. RT-PCR and western blotting were performed to
      detect mRNA and protein levels of p21 and p53 in K562 cells. HIF-1alpha mRNA
      expression in the bone marrow of CML patients was significantly higher than that
      in the control, which was statistically significant (P < 0.05). HIF-1alpha
      knockdown dramatically reduced the proliferation of K562 cells, which was also
      statistically significant (P < 0.05). HIF-1alpha knockdown markedly reduced the
      colony formation ability of K562 cells, which was also statistically significant
      (P < 0.05). The mRNA and protein expression of p21 were significantly reduced in
      K562 cell after HIF-1alpha knockdown with affecting the mRNA and protein levels
      of p53. HIF-alpha promotes chronic CML cell proliferation by up-regulating p21
      expression.

PMID- 25596668
TI  - [Dysfunction protesis mitral in a patient with Bland-White-Garland syndrome.
      First case advised in Latin America].

PMID- 25596669
TI  - Recovery of Olfactory Mediated Behaviours of Fish from Metal Contaminated Lakes.
AB  - Fish mediate many biological processes by olfaction, which can be impaired by
      contaminants (i.e. metals). While the olfactory recovery of fish from metal
      contaminated lakes if subsequently cultured in clean water has been shown at the
      neurophysiological level, the recovery potential of olfactory mediated behaviours
      remains unknown. To study behavioural recovery of fish from metal contaminated
      lakes, wild yellow perch (Perca flavescens) were collected from two metal
      contaminated lakes (Ramsey and Hannah lakes) in the metal-mining district of
      Sudbury, ON, Canada and cultured in clean water from a reference lake (Geneva
      Lake) for another 24 h. Olfactory mediated behaviours of the test organisms were
      tested using avoidance responses to conspecific skin extract. While olfactory
      mediated behaviours of fish from Ramsey Lake (low contamination) recovered after
      24 h in clean water, recovery could not be observed in fish from Hannah Lake
      (high contamination). These results demonstrate that the recovery of behavioural
      deficits of fish from metal contaminated lakes is depending on the habitats'
      metal concentration.

PMID- 25596670
TI  - Parametric fate and transport profiling for selective groundwater monitoring at
      closed landfills: a case study.
AB  - Monitoring contaminant concentrations in groundwater near closed municipal solid
      waste landfills requires long term monitoring program which can require
      significant investment for monitoring efforts. The groundwater monitoring data
      from a closed landfill in Florida was analyzed to reduce the monitoring efforts.
      The available groundwater monitoring data (collected over 20 years) were analyzed
      (i.e., type, concentration and detection level) to identify the trends in
      concentrations of contaminants and spatial mobility characteristics of
      groundwater (i.e., groundwater direction, retardation characteristics of
      contaminants, groundwater well depth, subsoil characteristics), to identify
      critical monitoring locations. Among the 7 groundwater monitoring well clusters
      (totaling 22 wells) in landfill, the data from two monitoring well clusters
      (totaling 7 wells) located along direction of groundwater flow showed
      similarities (the highest concentrations and same contaminants). These wells were
      used to assess the transport characteristics of the contaminants. Some parameters
      (e.g., iron, sodium, ammonia as N, chlorobenzene, 1,4-dichlorobenzene) showed
      decreasing trends in the groundwater due to soil absorption and retardation.
      Metals were retarded by ion exchange and their concentration increased by depth
      indicating soil reached breakthrough over time. Soil depth did not have a
      significant effect on the concentrations of volatile organic contaminants. Based
      on the analyses, selective groundwater monitoring modifications were developed
      for effective monitoring to acquire data from the most critical locations which
      may be impacted by leachate mobility. The adjustments in the sampling strategy
      reduced the amount of data collected by as much as 97.7% (i.e., total number of
      parameters monitored). Effective groundwater sampling strategies can save time,
      effort and monitoring costs while improving the quality of sample handling and
      data analyses for better utilization of post closure monitoring funds.

PMID- 25596672
TI  - [Distal revascularization in diabetic patients with chronic limb ischemia].
AB  - Diabetes mellitus is an independent risk factor for peripheral artery disease.
      Life expectancy is 41 months for diabetic patients with an ischemic ulcer. The
      characteristics of diabetic arteriopathy make its treatment more difficult than
      in non-diabetic patients. Few data are available about the surgical treatment of
      arteriopathy in diabetic patients (including angioplasty or bypass), especially
      in case of distal arteriopathy. The choice of the procedure depends on multiple
      factors such as the disease localization, its extent, distal blood flow and
      vascular disease-related surgical risk. The principal aim of revascularisation is
      to restore direct flow to the foot in order to ensure wound healing and limb
      salvage. With percutaneous endoluminal angioplasty, limb salvage can be achieved
      in more than 80% of patients at 1-3 years. The percutaneous procedure is less
      invasive than open surgery, there are fewer complications, and morbidity and
      mortality rates are reduced; moreover, a second procedure remains possible in the
      future. With bypass surgery, the rate of limb salvage exceeds 80% at five years.
      Nevertheless, peri-operative mortality reaches 3% and arterial anatomy, patient
      related risks factors or venous graft availability may be limitations. New
      endovascular techniques especially designed for the distal arteries of the lower
      limbs enable very distal revascularization with morbidity and mortality rates
      lower than with surgery.

PMID- 25596671
TI  - Protective Effects of Baicalin on Abeta1-42-Induced Learning and Memory Deficit,
      Oxidative Stress, and Apoptosis in Rat.
AB  - The accumulation and deposition of beta-amyloid peptide (Abeta) in senile plaques
      and cerebral vasculature is believed to facilitate the progressive
      neurodegeneration that occurs in the Alzheimer's disease (AD). The present study
      sought to elucidate possible effects of baicalin, a natural phytochemical, on
      Abeta toxicity in a rat model of AD. By morris water maze test, Abeta1-42
      injection was found to cause learning and memory deficit in rat, which was
      effectively improved by baicalin treatment. Besides, histological examination
      showed that baicalin could attenuate the hippocampus injury caused by Abeta. The
      neurotoxicity mechanism of Abeta is associated with oxidative stress and
      apoptosis, as revealed by increased malonaldehyde generation and TUNEL-positive
      cells. Baicalin treatment was able to increase antioxidant capabilities by
      recovering activities of antioxidant enzymes (superoxide dismutase, catalase, and
      glutathione peroxidase) and up-regulating their gene expression. Moreover,
      baicalin effectively prevented Abeta-induced mitochondrial membrane potential
      decrease, Bax/Bcl-2 ratio increase, cytochrome c release, and caspase-9/-3
      activation. In addition, we found that the anti-oxidative effect of baicalin was
      associated with Nrf2 activation. In conclusion, baicalin effectively improved
      Abeta-induced learning and memory deficit, hippocampus injury, and neuron
      apoptosis, making it a promising drug to preventive interventions for AD. 

PMID- 25596673
TI  - [Efficacy of TAS-102].
AB  - Of late, there has been rapid development of chemotherapeutic agents for treating
      metastatic colorectal cancers. However, the so-called "druglag" is a long
      standingproblem; it refers to the drugapproval delays in Japan that occur after
      drugs have been developed and approved in Europe and the USA. Clinical trials for
      the drugTAS -102 were stopped in the USA, but the drugwas evaluated in phase I
      and II clinical trials in Japan. The Phase II trial for TAS-102 in Japan provided
      positive results, and it received approval in Japan first, ahead of the world.
      Data from the global phase III RECOURSE trial were presented in the ESMO-GI 2014,
      where the efficacy of TAS-102 was proved again. Herein, we present data about the
      efficacy and side effects of TAS-102 from each clinical trial. 

PMID- 25596674
TI  - [Treatment of advanced non-small-cell lung cancer in elderly patients].
AB  - Japan has the highest percentage of elderly population in the world;
      consequently, Japan has an aging society that is not observed in other countries.
      Lung cancer is the leading cause of cancer deaths in Japan. Consequently, it has
      become increasingly important to establish an effective treatment regimen for
      elderly patients with advanced non-small-cell lung cancer (NSCLC). Standard first
      line chemotherapy for younger patients with stage IV NSCLC includes platinum
      combination therapy. However, two standard options are available for elderly
      patients with advanced NSCLC. The first is single agent chemotherapy, and the
      second is doublet chemotherapy. Treatment options should be tailored for elderly
      patients based on the comprehensive evaluation and the evidence from clinical
      trials for. This article reviews the available data on radiation therapy and
      systemic chemotherapy for elderly patients with NSCLC, and assesses the role of
      comprehensive geriatric assessment (CGA) in the evaluation of elderly patients.

PMID- 25596675
TI  - [Chemotherapy for gastrointestinal cancer patients in elderly].
AB  - It is expected that incidence of gastrointestinal cancers in elderly would
      increase. However limited data for chemotherapy is available for such patients.
      Elderly patients with good condition are considered as candidates for standard
      chemotherapy. Prolonged survival is expected even in elderly patients same as
      young with caution for toxicity. Decisions to deliver combination chemotherapy
      are to be dependent on status of comorbidity. Personalized approach is highly
      recommended because of insufficiency of organic functions, which is not apparent
      with standard examinations. For some patients to start with one level reduced
      dosage is reasonable with intent to escalation and de-escalation based on adverse
      events. Importance of prospective randomized trial would never diminish for
      elderly. 

PMID- 25596676
TI  - [Activity of the JCOG geriatric study committee and chemotherapy of colorectal
      cancer in older patients].
AB  - Japan Clinical Oncology Group (JCOG) is a largest cooperative group in Japan,
      funded by the ministry of health, labor and welfare of Japanese government. We
      just established the Geriatric Study Committee in December 2013. The goal of this
      committee is to make a policy to promote clinical trials for older patients with
      3 major tasks: (1) Create a clear and operational definition of
      vulnerability/frailty applicable to oncology,(2)Develop, test and disseminate
      geriatric assessments, (3) Improve research in the field of geriatric oncology,
      in collaboration with SIOG. JCOG1018 is a randomized phase III study of mFOLFOX7
      or CAPOX plus bevacizumab versus 5-fluorouracil/Leucovorin or capecitabine plus
      bevacizumab as first-line treatment in elderly patients with metastatic
      colorectal cancer. This study includes geriatric assessments (VES-13) before
      chemotherapy.

PMID- 25596677
TI  - [Dose optimization of anticancer drugs in the elderly].
AB  - Age-related physiological changes affect pharmacokinetics and pharmacodynamics in
      elderly individuals. Cancer treatment in the elderly requires a careful and
      multidisciplinary assessment of each patient prior to therapy initiation with
      respect to treatment decisions and dose optimization considerations, given the
      wide interpatient variability in this population. As renal function declines with
      age, renal function assessments are necessary when drugs increasing exposure in
      renal impairment will be administered to elderly patients. Serum creatinine is an
      insufficient marker for evaluating renal function in elderly patients because
      muscle mass decreases with age. Renal function should be assessed according to
      the index used for dosing recommendation at drug administration planning; in most
      of drugs, does adjustment is recommended according to the creatinine clearance
      (Ccr) calculated using the Cockcroft-Gault equation. Elderly patients are
      apparently more sensitive to cytotoxic agent-induced neutropenia and therefore
      should be monitored closely. Following the first cycle, a proper assessment of
      tolerability should be conducted before the second cycle; such assessments are
      required to discuss the appropriateness of the initiation dose and determine
      doses during the following cycles for each patient.

PMID- 25596679
TI  - [Outpatient reinduction therapy with gemcitabine, dexamethasone, Cisplatin (GDP)
      for patients with relapsed and refractory lymphoma].
AB  - For younger patients with relapsed or refractory lymphomas who respond to salvage
      therapy, autologous stem cell trans- plantation(ASCT)is the standard of care.
      Recently, it was demonstrated that the gemcitabine/dexamethasone/cisplatin (GDP)
      regimen for patients with relapsed or refractory aggressive non-Hodgkin's
      lymphoma (NHL) prior to ASCT was not inferior to the standard
      dexamethasone/cytarabine/cisplatin (DHAP) regimen for patients with relapsed and
      refractory aggressive lymphoma. In Japan, most patients who receive CDDP
      containing regimens are hospitalized because of the substantial transfusions
      required for preventing renal dysfunction. We initiated GDP therapy combined with
      a short period of hydration and the administration of a magnesium agent and
      mannitol for 5 patients with relapsed and refractory aggressive lymphoma. In 4
      cases, GDP was safely administered on an outpatient basis. Furthermore,
      peripheral blood stem cells were successfully collected in 2 patients. After stem
      cell harvest, ASCT was performed in a patient with diffuse large B-cell lymphoma,
      with the patient remaining in complete remission (CR) after ASCT.

PMID- 25596678
TI  - [Effect of weekly paclitaxel followed by 5-fluorouracil, epirubicin, and
      cyclophosphamide as neoadjuvant treatment for patients with triple-negative and
      luminal-type breast cancer - a multicenter study].
AB  - This study examined the pathological complete response (pCR )rate and safety of
      induction chemotherapy with 12 cycles of weekly paclitaxel (80 mg/m2) followed by
      4 cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclo-
      phosphamide (500 mg/m2). The study medication was administered to female patients
      (n=31)with a mean age of 51 years, diagnosed with stage II A (n=18), II B (n=11)
      and III A (n=2) disease and with an estrogen receptor positive rate of 65%
      (20/31). No patient was HER2-IHC [human epidermal growth factor receptor 2 (HER2)
      immunohistochemistry (IHC)](3+) or HER2-FISH (fluorescence in situ hybridization)
      positive. Twenty-eight patients completed the treatment regimen. Treatment was
      halted in 2/31 patients due to progression of disease in one patient and a Grade
      3 non-hematological adverse effect of skin eruption and itching in the other
      patient. A third patient died of causes unrelated to the study medication.
      Central review ascertained a pCR in 6 patients. In patients with triple-negative
      disease we observed a pCR rate of 67% (6/9). In patients with the Luminal (A+B)
      subtype, 0% (0/19) had a pCR. Grade 3/4 toxicity included leucopenia (58%),
      neutropenia (58%), febrile neutropenia (26%), fatigue (10%), and ALT elevation
      (7%). In terms of pCR, patients presenting with triple-negative disease and
      manageable safety profiles appear to respond well to this treatment regimen,
      while only a modest response was observed in patients with Luminal subtype
      disease.

PMID- 25596680
TI  - [Feasibility of short volume hydration in patients with lung cancer treated with
      Cisplatin-containing chemotherapy].
AB  - The aim of this study was to examine the feasibility of short volume hydration
      (SH) with magnesium and mannitol versus normal high volume hydration (NH) for
      targeting nephrotoxicity in lung cancer patients treated with cisplatin (CDDP)-
      containing chemotherapy. Between January 2012 and February 2013, 28 patients with
      lung cancer at a single institute received CDDP-containing chemotherapy. We
      retrospectively evaluated the incidence of nephrotoxicity during the first cycle
      of chemotherapy. Nephrotoxicity was compared between the SH and NH regimens
      according to the Common Terminology Criteria for Adverse Events(CTCAE) version
      4.0. Laboratory data were collected from the 2 regimen groups at pre-treatment,
      during the first cycle, and post-treatment and were compared by univariate
      analysis. Twelve patients received the SH regimen with magnesium and mannitol,
      and 16 patients received the NH regimen. Only 1 patient in the NH regimen group
      had Grade 2 increases in serum creatinine. On the other hand, no patient in the
      SH regimen group had increased serum creatinine. There was no significant
      difference in the incidence of nephrotoxicity between the 2 regimen groups during
      the first cycle of CDDP induction(p=0.38). The SH regimen with magnesium and
      mannitol is feasible in lung cancer patients treated with CDDP-containing
      chemotherapy.

PMID- 25596681
TI  - [Switching from oral oxycodone to oxycodone injection - an investigation into the
      dosage amount ratio].
AB  - In switching from oraloxycodone to oxycodone injection, clinical guidelines
      recommend a conversion dose ratio of 0.75. However, in clinical sites, a higher
      dosage may be needed due to characteristics of cancer pain. In the present study,
      we investigated changing the dosage amount of oxycodone before and after
      switching from oraloxycodone administration to oxycodone injection in patients
      (n=14) who reported suffering from cancer pain. As a result, we found the ratio
      of the amount used after switching to be 0.91 +/- 0.25 (mean +/- SD) on the first
      day, increasing to 1.46 +/- 0.48 on the fifth day. Our findings suggest that the
      dosage amount was the correct one for each patient's condition and also that
      adequate injection dosage to manage cancer pain was greater than that of
      calculated by the conversion ratio.

PMID- 25596682
TI  - [Everolimus plus exemestane in postmenopausal patients with estrogen-receptor
      positive advanced breast cancer - Japanese subgroup analysis of BOLERO -2].
AB  - In a phase 3, double-blind, randomized, international study (the BOLERO-2), the
      addition of mTOR inhibitor everolimus to exemestane was evaluated in
      postmenopausal women with estrogen-receptor-positive (ER+) advanced/recurrent
      breast cancer that was refractory to any nonsteroidal aromatase inhibitor (NSAI).
      This report presents the safety and updated (18- month) efficacy results from the
      Japanese subset (n=106) of BOLERO-2. After a median follow-up of 18 months, the
      median progression-free survival time was 8.5 months with everolimus plus
      exemestane compared to 4.2 months with placebo plus exemestane. The most common
      adverse events (AEs) with everolimus plus exemestane were stomatitis, rash,
      dysgeusia, and non-infectious lung disease. The AEs reported with the combination
      therapy were mostly of grade 1 or 2 and manageable with appropriate intervention.
      In conclusion, this combination could be a useful addition to the armamentarium
      of treatments for Japanese postmenopausal women with ER+ advanced/recurrent
      breast cancer progressing on NSAIs.

PMID- 25596683
TI  - [Safety management of intravenous cancer chemotherapy and oral premedication
      drugs].
AB  - The administration of oral premedication drugs (OPDs) is increased before
      intravenous cancer chemotherapy to prevent adverse events such as
      hypersensitivity or nausea and vomiting. As intravenous chemotherapy regimens and
      OPDs are ordered separately in the electronic medical record system, the
      prescription or administration of OPDs may be missed. To overcome this problem,
      we developed a combination regimen ordering (CRO) system, in which OPDs were
      included in the intravenous chemotherapy regimen enabling simultaneous ordering.
      This system used the electronic medical record system HAPPY ACTIS by TOSHIBA
      Medical Information Systems Co. in our hospital. OPDs were prepared in an
      envelope labeled with a bar code to identify the patient, which was then used by
      the nursing staff to administer the medication. Between August 2011 and January
      2014, CRO systems were used in 66 regimens for the treatment of the following
      cancers: 21 lung cancers, 14 breast cancers, 9 hematologic malignancies, 7
      genitourinary cancers, 6 gastrointestinal cancers, 5 gynecological cancers, 3
      head and neck cancers, and 1 dermatological malignancy. The OPDs administered
      were diphenhydramine, loxoprofen, chlorpheniramine, aprepitant, and ramosetron.
      Although we were unable to check OPDs in the oral drug administration histories,
      no errors in the administration of OPDs have been reported after the adoption of
      the CRO system. Therefore, our CRO system improved the safety and quality of
      patient care for cancer chemotherapy.

PMID- 25596684
TI  - [Prolonged remission achieved by using bevacizumab plus paclitaxel therapy
      combined with sequential radiotherapy for a rapidly growing chest wall recurrence
      of triple negative breast cancer - a case report].
AB  - A 73-year-old woman, who was diagnosed with right triple negative breast cancer
      (cT1cN1M0, stage I ) and underwent right modified radical mastectomy with
      axillary lymph node dissection, showed recurrent disease in the right parasternal
      lymph node 4 years after the operation. Computed tomography (CT) revealed rapid
      growth of the tumor along with pain, accompanied by the destruction of the
      sternal bone. Five cycles of bevacizumab plus paclitaxel (BEV+wPTX) treatment (10
      mg/kg of bevacizumab on days 1 and 15 plus 90 mg/m2 of paclitaxel on days 1, 8,
      and 15 every 4 weeks)achieved remarkable tumor regression. Parasternal
      irradiation (30 Gy/15 Fr) followed by oral capecitabine treatment (600 mg b. i.
      d; 3 week administration followed by a week of rest) as maintenance therapy
      showed complete tumor regression and helped to achieve good quality of life (QOL)
      without any unfavorable symptoms at the 2-year follow-up, although the estimated
      progression free survival of this treatment is about 6 months. As BEV+wPTX had a
      high response rate for recurrent breast cancer, its combination with sequential
      radiotherapy could provide a favorable local control rate and good QOL for
      patients with rapidly growing, solitary, recurrent breast cancers.

PMID- 25596685
TI  - [A case of advanced gastric cancer responding to S-1/CDDP neoadjuvant
      chemotherapy, leading to a pathological complete response].
AB  - A 66-year-old man with cStage III B (cT4aN2H0P0M0) advanced gastric cancer in the
      cardia with esophageal invasion was treated with S-1/CDDP as neoadjuvant
      chemotherapy. After 3 courses of chemotherapy, a significant reduction in tumor
      burden was observed. Total gastrectomy and splenectomy with lymph node dissection
      (D2) were performed. Pathological specimens showed no cancer cells in the stomach
      and lymph nodes, indicating a pathological complete response.

PMID- 25596687
TI  - [A case of liver and para-aortic lymph node metastasis of colorectal cancer
      responding to S-1].
AB  - A 78-year-old woman was diagnosed with liver and para-aortic lymph node
      metastasis of colorectal cancer via abdominal computed tomography (CT) during a
      post-operative follow-up. She and her family declined intensive chemotherapy.
      Therefore, reduced S-1 (80 mg/body/day) was administered for 2 weeks followed by
      a 2 week interval. After 5 courses, CT revealed a complete response for the liver
      metastasis and a partial response for the para-aorticlymph node metastasis.
      Twenty-four courses of chemotherapy were completed, and only a follow-up CT
      examination was performed. The paraaorticlymph node grew larger, but the liver
      metastasis did not reappear. Herein, we report a case that showed a good response
      to S-1.

PMID- 25596686
TI  - [A case of recurrent gastric cancer successfully treated with S-1 oral
      administration].
AB  - This report describes a case of recurrent gastric cancer successfully treated
      with S-1 oral administration. A 77-year old female patient underwent distal
      gastrectomy for gastric cancer, followed by adjuvant chemotherapy with tegafur
      uracil (UFT). However, 1 year after surgical resection, recurrence in the lymph
      node of the hepatic hilum was diagnosed by abdominal computed tomography. The
      patient was treated with S-1 alone after refusing in travenous infusion
      chemotherapy. Three months after treatment, the size of the target lesion
      decreased significantly, and a complete response was seen on imaging examination
      during the 2 years of chemotherapy treatment. One year and 5 months after the
      discontinuation of chemotherapy, recurrence was noted again. Although supportive
      care was eventually provided to the patient, S-1 oral administration was resumed
      that resulted in tumor growth control for>6 months. In this patient, S-1
      treatment was effective in tumor growth suppression without deteriorating the
      patient's quality of life (QOL). Further studies are needed to identify patients
      for whom S-1 therapy is optimal treatment.

PMID- 25596688
TI  - [A case of multiple liver metastases from colon cancer treated with complete
      resection via two-stage hepatectomy after regeneration of the liver].
AB  - A 55-year-old woman underwent low anterior resection for sigmoid colon cancer
      with multiple bilobar metastases. She then received 23 courses of Leucovorin,
      fluorouracil, and oxaliplatin (mFOLFOX) plus bevacizumab and 13 courses of
      Leucovorin, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab as down
      staging chemotherapy. A two-stage hepatectomy was planned to avoid the risk of
      hepatic failure due to radial resection of bilobar metastases. Therefore, a right
      lobectomy was performed, and curative resection was achieved 54 days after the
      first hepatectomy. Two-stage hepatectomy as well as a combination of induction
      chemotherapy and portal vein embolization may have contributed to the improved
      prognosis of the initially unresectable multiple bilobar liver metastases.

PMID- 25596689
TI  - [Complete resection of liver metastases of colorectal cancer after high efficacy
      bevacizumab, S-1, and CPT -11 combination chemotherapy].
AB  - We describe a case of liver metastasis of colorectal cancer that became
      resectable after bevacizumab (Bmab), CPT-11, and S-1 ie Bmab+IRIS combination
      chemotherapy. A 65-year-old man experienced repeated constipation and diarrhea in
      August of 2013. Colonoscopy was conducted by a local doctor, and a
      tumor(diagnosed as adenocarcinoma tub1 by biopsy)was found in the upper rectum.
      Computed tomography performed at our institution detected synchronous liver
      metastasis. On September 9, laparoscopic rectal anterior resection was performed
      to prevent metastasis to the ileus, and on October 9, the patient began receiving
      Bmab+IRIS combination chemotherapy. Before chemotherapy, 3 metastases with a
      maximum diameter of 7 cm diameter)were observed in the right lobe of the liver.
      After 4 courses of chemotherapy, their maximum diameter was 3 cm, which allowed
      resection. Ultimately, the metastases were completely resected. Conversion of non
      optimal resection cases of liver metastases to optimal cases by using Bmab+IRIS
      chemotherapy is extremely rare. We suggest that Bmab+IRIS chemotherapy could be
      an option for conversion of non optimal liver resection cases to optimal cases.
      We report this rare case and discuss the implications of adjuvant chemotherapy
      for this patient.

PMID- 25596691
TI  - [Preoperative chemotherapy with modified FOLFOX + panitumumab for the treatment
      of descending colon cancer with multiple liver metastases - a case study].
AB  - A 40-year-old woman visited her primary care physician because she had pain in
      the upper right part of the abdomen. She was diagnosed with descending colon
      cancer with multiple liver metastases, and was referred to our department. After
      a laparoscopic abdominal colectomy for removal of the original lesion,
      chemotherapy was initiated with a modified combination of folinic acid, 5
      fluorouracil, and oxaliplatin (mFOLFOX6) + panitumumab. After 12 courses of
      treatment with the mFOL FOX6 + panitumumab combination, followed by 13 courses of
      the simplified biweekly 5-fluorouracil and Leucovorin (sLV5FU2) + panitumumab
      combination, her liver tumors had regressed to about 90% of their original size.
      A laparoscopic partial hepatectomy was successfully performed. Histopathological
      examination indicated a Grade 2 regression of the tumor in response to
      chemotherapy. This report highlights the effectiveness of "conversion therapy"
      after chemotherapy with the mFOLFOX6+panitumumab combination, especially in those
      patients with multiple liver metastases from colorectal cancer.

PMID- 25596690
TI  - [A case of long-term survival after peritoneal recurrence of rectal cancer
      achieved by tumorectomy and adjuvant chemotherapy].
AB  - The patient was a 40-year-old woman.She began experiencing abdominal pain and
      constipation in July 2005.S he underwent endoscopy in August, which revealed
      rectal cancer.She was referred to our hospital for surgery and underwent anterior
      resection with lymph node dissection in September. The pathological diagnosis was
      tub2, SS, N2, ly1, v1, stage III b. After discharge, she began oral chemotherapy.
      However, in April 2006, computed tomography (CT) revealed recurrence in the
      Douglas pouch. She began FOLFOX4 treatment in May.On follow-up CT performed in
      July, the recurrent sites were limited to 2 nodules and were deemed resectable.
      The patient underwent peritoneal dissemination resection, and the pathological
      diagnosis was metastatic tumor.She subsequently received 11 postoperative FOLFOX4
      courses. The chemotherapy regimen was changed to the de Gramont regimen because
      of peripheral neuropathy. After 56 courses of the de Gramont regimen, the
      chemotherapy regimen was further changed to UFT/UZEL. The patient received 28
      additional courses but experienced hair loss and requested treatment cessation.
      To date, she remains alive without recurrence.

PMID- 25596692
TI  - [A case of disease-free, long survival in a patient with mixed
      adenoneuroendocrine carcinoma of the gallbladder treated with induction CDDP/CPT
      11 chemotherapy and resection].
AB  - A 57-year-old woman with a complaint of a right upper quadrant mass was referred
      to our hospital. Multimodal studies such as PET-CT revealed large hepatic tumors
      and swollen para-aortic lymph nodes, the origin of which was unclear.
      Pathological analysis of a biopsy specimen obtained from the liver tumor led to a
      diagnosis of neuroendocrine carcinoma. After 4 CDDP/CPT-11 chemotherapy treatment
      courses, remarkable shrinkage of liver tumors and disappearance of the swollen
      lymph nodes were achieved. Subsequently, liver tumor and extrahepatic bile duct
      resection and lymphatic dissection were performed. Pathological analysis of the
      resected specimens revealed that the liver tumors and metastatic lymph nodes
      originated from the gallbladder, leading to a diagnosis of mixed
      adenoneuroendocrine carcinoma. After 5 courses of adjuvant chemotherapy using the
      same regimen, the patient has remained disease free for 24 months since the
      initialdiagnosis. 

PMID- 25596693
TI  - [A case of primary mediastinal (Thymic) B-cell lymphoma successfully treated with
      the DA-EPOCH-R Regimen].
AB  - Primary mediastinal (thymic) B-cell lymphoma (PMBL) is resistant to treatment
      when compared with diffuse large B-cell lymphoma (DLBCL). Moreover, the optimal
      first -line treatment of PMBL has not yet been determined. Herein, we report a
      case of PMBL that was successfully treated with the dose adjusted (DA) etoposide,
      prednisolone, vincristine, doxorubicin, and cyclophosphamide with rituximab
      (EPOCH-R) regimen. A-29-year-old woman was referred to our hospital with an
      anterior mediastinal tumor. Eight months before admission, she had visited a
      clinic for pain in the chest and back, but no abnormalities were found.
      Subsequently, her chest pain got worse, and she went to another clinic, where she
      was detected with an anterior mediastinal tumor and was referred to our hospital.
      Tumor biopsy with a thoracoscope was performed, and a diagnosis of PMBL was made.
      The tumor diameter was 90 mm, with invasion to the lungs and superior vena cava.
      The tumor had a clinical stage of IEA, and the International Prognostic Index
      (IPI) was low risk. She was treated with the DA-EPOCH-R regimen for 8 courses,
      and a complete response was achieved. A recent retrospective study of DA-EPOCH-R
      treatment without radiotherapy for PMBL was recently published. It showed that
      the event-free survival rate was 93% and the overall survival rate was 97% during
      a median 5-year follow-up. Thus, DA-EPOCH-R may be a potential standard treatment
      for PMBL.

PMID- 25596694
TI  - [A case of lacrimal duct obstruction caused by capecitabine].
AB  - In recent years, the incidence of adverse ocular reactions, including corneal
      problems and lacrimal duct obstruction, due to antineoplastic agents such as S-1
      has increased. Very few reports of adverse ocular reactions caused by
      capecitabine, a fluorinated pyrimidine antineoplastic agent like S-1, exist, and
      consequently, the mechanism underlying these reactions is not well understood.
      This report describes our recent experience with a case of lacrimal duct
      obstruction caused by capecitabine. The patient was a 71-year-old woman who was
      being administered trastuzumab plus capecitabine combination chemotherapy for
      breast cancer-related bone metastasis. She complained of epiphora 7 days after
      capecitabine was initiated. Thereafter, her capecitabine dose was reduced owing
      to exacerbation of hand-foot syndrome, but the epiphora persisted. Capecitabine
      was discontinued 287 days after initiation owing to exacerbation of the hand-foot
      syndrome. However, because the epiphora persisted, the patient visited the
      ophthalmology department. The ophthalmologist diagnosed the patient with
      binocular nasolacrimal duct obstruction and cataract, and prescribed a 0.3%
      gatifloxacin ophthalmic solution and 0.1% fluorometholone ophthalmic suspension.
      Thereafter, the epiphora reduced. When the patient returned to the ophthalmology
      department, symptom improvement was confirmed. In this case, lacrimal duct
      obstruction likely developed due to capecitabine. The symptoms were reversible
      with discontinuation of capecitabine and ophthalmic treatment. We believe that
      reporting this case could be valuable in discussing capecitabine-induced lacrimal
      duct obstruction.

PMID- 25596695
TI  - [Suspected dihydropyrimidine dehydrogenase deficiency in a patient receiving
      capecitabine as adjuvant chemotherapy after colon resection].
AB  - We report here the case of a 75-year-old male patient who developed severe side
      effects after treatment with capecitabine (Xeloda(r)) that he received as
      adjuvant chemotherapy. He was suspected to have partial dihydropyrimidine
      dehydrogenase (DPD) deficiency. The patient underwent sigmoidectomy for sigmoid
      cancer and was treated with capecitabine as adjuvant chemotherapy. He was
      admitted to our hospital 14 days after the start of treatment with appetite loss,
      diarrhea, and a high body temperature. After admission, he developed severe
      neurotoxicity (Grade 4). We measured the DPD activity in peripheral mononuclear
      cells, which indicated partial DPD deficiency.

PMID- 25596696
TI  - [Reinforcement of warfarin action in a patient administered S-1].
AB  - A case showing reinforcement of the action of warfarin and potassium in a patient
      administered S-1 is reported.The patient was a 71-year-old man with left upper
      gingival cancer.He had ventricular tachycardia (VT), hypertrophic cardiomyopathy,
      and a cerebellar infarction.He underwent a pacemaker implantation, and was
      administered warfarin.After the operation, in mid-March 2010, he was administered
      with S-1 and warfarin. However, the international normalized ratio of prothrombin
      time (PT-INR) increased to an extremely high level of 5.82, and S-1 and warfarin
      were stopped. They were re-administered at the end of April, and the PT-INR
      stabilized to approximately 2.

PMID- 25596697
TI  - Influence of topical application of capsaicin, menthol and local anesthetics on
      intraoral somatosensory sensitivity in healthy subjects: temporal and spatial
      aspects.
AB  - The aim of this study was to investigate temporal and spatial aspects of
      somatosensory changes after topical application of capsaicin, menthol and local
      anesthetics (LA) on the gingiva with the use of intraoral palpometers and thermal
      devices. Sixteen healthy volunteers (eight male, eight female) participated. Four
      topical preparations (capsaicin, menthol, LA and Vaseline as a control) were
      randomly applied to the gingiva around the first premolar in the upper jaw via
      individual oral templates, which allowed spatial mapping of somatosensory changes
      at and adjacent to the site of application. The topical drugs were applied for 15
      min in a randomized and balanced sequence. The perceived preparation-evoked pain
      intensity was recorded with the use of 0-10 visual analog scales (VAS).
      Standardized mechanical and thermal stimuli were applied before, during and up to
      30 min after the topical applications, and numerical rating scales (NRS) were
      used to score the perceived intensity of the stimuli. Peak VAS, area under the
      curve and mean VAS preparation-evoked pain scores for capsaicin, menthol, LA and
      control were compared with paired t tests. NRS scores for mechanical and thermal
      test stimuli were analyzed with four-way repeated measurements analyses of
      variance. Capsaicin evoked significantly higher VAS pain parameters as well as
      higher NRS scores to heat stimuli than control (P < 0.029). There were no
      significant differences in stimulus-evoked NRS scores between the menthol and
      control conditions (P = 0.518), but LA caused significantly lower stimulus-evoked
      NRS scores compared with control (P < 0.001). Post hoc tests showed that
      capsaicin caused sensitization to heat stimuli at and adjacent to the application
      area. In conclusion, this study for the first time demonstrates the time course
      of capsaicin-evoked heat hyperalgesia in and outside the site of application at
      the oral mucosa (primary and secondary hyperalgesia).

PMID- 25596698
TI  - PGRMC1 contributes to doxorubicin-induced chemoresistance in MES-SA uterine
      sarcoma.
AB  - Chemotherapy is one of the major categories of medical oncology and a primary
      tumor treatment; however, the effectiveness of chemotherapy is restricted by drug
      resistance. Overcoming resistance to chemotherapy and investigating molecular
      targeted therapies are challenges currently faced during resistance management.
      Progesterone receptor membrane component 1 (PGRMC1) is an adapter protein
      mediating cholesterol synthesis, steroid signaling, and cytochrome p450
      activation. Attention has recently focused on the role of PGRMC1 in cell
      survival, anti-apoptosis, and damage response. In the present study, we used
      knockdown and overexpression approaches in the following set of uterine sarcoma
      models to further evaluate the role of PGRMC1 in drug resistance: the doxorubicin
      sensitive MES-SA cells and the doxorubicin-resistant MES-SA/DxR-2 uM and MES
      SA/DxR-8 uM cells (with different levels of doxorubicin resistance). PGRMC1
      repressed doxorubicin-induced cytotoxicity and exhibited an anti-apoptotic
      effect; it also promoted cell proliferation and cell cycle progression to the S
      phase. Of note, PGRMC1 overexpression led to the epithelial-mesenchymal
      transition (EMT) of the sensitive MES-SA cells, thus facilitating their migration
      and invasion. The combination of PGRMC1 knockdown and the P-glycoprotein
      inhibitor verapamil significantly decreased the viability of P-glycoprotein
      overexpressing MES-SA/DxR-8 MUM cells after doxorubicin treatment. Taken
      together, our results show that PGRMC1 contributed to chemoresistance through
      cell proliferation, anti-apoptosis, and EMT induction, leading to the suggestion
      that PGRMC1 may serve as a therapeutic target in combination with an inhibitor in
      different drug resistance pathways and indicating the usefulness of predictive
      resistance biomarkers in uterine sarcoma.

PMID- 25596700
TI  - Prognostic values of ERK1/2 and p-ERK1/2 expressions for poor survival in non
      small cell lung cancer.
AB  - The extracellular-regulated kinase (ERK) 1/2, as a member of the mitogen
      activated protein kinase family, plays a crucial role in the development of
      cancer. However, little is known about the prognostic value of ERK1/2 and
      phosphorylated ERK1/2 (p-ERK1/2) in non-small cell lung cancer (NSCLC). Thus, we
      investigated their prognostic values and analyzed the associations between their
      expressions and clinicopathological features in NSCLC patients. We examined
      ERK1/2 and p-ERK1/2 expressions via immunohistochemistry in 183 NSCLC samples.
      The prognostic significances of protein expression were evaluated with univariate
      and multivariate survival analysis. Of the specimens, 44.8 and 44.3 % revealed
      positive staining for ERK1/2 and p-ERK1/2, respectively. There were 24.6 %
      specimens with both ERK1/2 and p-ERK1/2-positive expression. The results showed p
      ERK1/2-positive expression was an independent prognostic factor for poor overall
      survival (OS) in NSCLC patients on both univariate analysis (p < 0.0001) and
      multivariate analysis (p = 0.0000). Meanwhile, the positive expression of both
      proteins was also associated with poor OS (p = 0.002). With respect to
      clinicopathological features, the tumor differentiation was significantly
      associated with the positivity of ERK1/2, p-ERK1/2, and both proteins, while
      histological type was only related to ERK1/2. However, there were no significant
      differences between the expressions and other clinical features, such as gender,
      age, smoking, tumor-node-metastasis (TNM) stage, lymph node metastasis, and
      treatments. The p-ERK1/2-positive expression was associated with adverse
      outcomes, and the positive expression of both ERK1/2 and p-ERK1/2 proteins was
      also related to poor OS. Therefore, the positivity of p-ERK1/2 expression may
      serve as a vital biomarker in the development of NSCLC.

PMID- 25596699
TI  - Independent and combined association of overall physical fitness and subjective
      well-being with fibromyalgia severity: the al-Andalus project.
AB  - PURPOSE: The present study aimed: (1) to test the associations of overall
      physical fitness and subjective well-being with fibromyalgia severity and (2) to
      determine whether the combination of overall physical fitness and subjective well
      being is associated with fibromyalgia severity among adult women patients.
      METHODS: This cross-sectional study included 424 participants from Andalusia,
      southern Spain. Overall physical fitness and the components of subjective well
      being (positive affect, negative affect and cognitive well-being), and
      fibromyalgia severity were assessed using the Functional Senior Physical Fitness
      Test Battery, the Positive and Negative Affect Schedule, the Satisfaction With
      Life Scale, and the Fibromyalgia Impact Questionnaire, respectively. RESULTS:
      Overall physical fitness (beta = -.23), positive affect (beta = -.18), negative
      affect (beta = .26), and cognitive well-being (beta = -.18) were all associated
      with fibromyalgia severity. The patients with the highest overall physical
      fitness and increased subjective well-being reported ~15 % lower fibromyalgia
      severity than those with the lowest fitness and poorest subjective well-being
      (Cohen's d > 1.0). CONCLUSION: Our results suggest that higher levels of overall
      physical fitness and subjective well-being are independently associated with
      lower fibromyalgia severity. Moreover, patients with higher overall physical
      fitness and increased subjective well-being (high positive affect, low negative
      affect, or high cognitive well-being) reported lower fibromyalgia severity than
      those with low levels of overall physical fitness and subjective well-being.

PMID- 25596701
TI  - Everolimus-based combination for the treatment of advanced gastroenteropancreatic
      neuroendocrine neoplasms (GEP-NENs): biological rationale and critical review of
      published data.
AB  - Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a
      heterogeneous group of diseases. Advanced GEP-NENs are considered distinct
      disease entity with limited treatments. In this review, we will explore the
      biological rationale and clinical data of everolimus-based combinations for
      advanced GEP-NENs. PubMed/Medline, the Cochrane Library, and Google Scholar were
      searched using the terms "GEP-NENs" and "everolimus" and "systemic therapy" and
      selecting English literature only. Outcomes of interest included progression-free
      survival and overall survival (PFS and OS), toxicities, and tumor response. A
      total of 14 potentially relevant trials were initially identified, of which five
      studies were excluded. Hence, nine trials including 699 patients were included.
      Median PFS was reported in four out of the nine studies ranging from 14.6 to 16.4
      months. The disease control rate was reported in all studies, and it ranged from
      75 to 93%. Frequently reported grade 3/4 toxicities were elevated transaminases,
      hyperglycemia, and hematologic toxicities. The presence of clinical and
      statistical heterogeneity of the primary studies precludes reliable evidence
      based conclusions. Further well-conducted randomized controlled trials are
      awaited to better evaluate the treatment of GEP-NENs.

PMID- 25596702
TI  - Prognostic value of ERCC1, ERCC2, XRCC1, and TP53 single nucleotide polymorphisms
      in patients with early-stage non-small cell lung cancer.
AB  - Identification of biomarkers used for the prognostic evaluation of non-small cell
      lung cancer (NSCLC) patients is important. The aim of this study was to evaluate
      the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide
      polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130
      patients, surgically treated for NSCLC between 2000 and 2012, were included. An
      analysis of SNPs from peripheral blood cells was performed by polymerase chain
      reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro
      polymorphisms were evaluated in conjunction with clinical and pathological
      parameters and survival. Kaplan-Meier method and Cox regression analysis were
      used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse
      free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC
      allele, median RFS was detected as 28.3 months (95 % confidence interval (CI),
      20.8-35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6-75.2), and
      80.1 months for those with TT mutant allel (95 % CI, 33.0-127.2). Median RFS was
      seen to be longer in mutant group and also statistically significant (P = 0.018).
      Additionally, upon evaluating CC normal group with CT + TT alleles including
      mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6-88.4) in CT +
      TT group, and this was statistically significant (P = 0.005) Also, median RFS was
      15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele
      in the group with no adjuvant treatment (P = 0.001). In conclusion, our study
      showed that ERCC2/XPD polymorphism is an independent prognostic factor in
      operated NSCLC patients, and these findings should be supported with prospective
      studies.

PMID- 25596703
TI  - Acquisition of docetaxel resistance in breast cancer cells reveals upregulation
      of ABCB1 expression as a key mediator of resistance accompanied by discrete
      upregulation of other specific genes and pathways.
AB  - The microtubule-targeting taxanes are important in breast cancer therapy, but no
      predictive biomarkers have yet been identified with sufficient scientific
      evidence to allow clinical routine use. The purposes of the present study were to
      develop a cell-culture-based discovery platform for docetaxel resistance and
      thereby identify key molecular mechanisms and predictive molecular
      characteristics to docetaxel resistance. Two docetaxel-resistant cell lines,
      MCF7RES and MDARES, were generated from their respective parental cell lines MCF
      7 and MDA-MB-231 by stepwise selection in docetaxel dose increments over 15
      months. The cell lines were characterized regarding sensitivity to docetaxel and
      other chemotherapeutics and subjected to transcriptome-wide mRNA microarray
      profiling. MCF7RES and MDARES exhibited a biphasic growth inhibition pattern at
      increasing docetaxel concentrations. Gene expression analysis singled out ABCB1,
      which encodes permeability glycoprotein (Pgp), as the top upregulated gene in
      both MCF7RES and MDARES. Functional validation revealed Pgp as a key resistance
      mediator at low docetaxel concentrations (first-phase response), whereas
      additional resistance mechanisms appeared to be prominent at higher docetaxel
      concentrations (second-phase response). Additional resistance mechanisms were
      indicated by gene expression profiling, including genes in the interferon
      inducible protein family in MCF7RES and cancer testis antigen family in MDARES.
      Also, upregulated expression of various ABC transporters, ECM-associated
      proteins, and lysosomal proteins was identified in both resistant cell lines.
      Finally, MCF7RES and MDARES presented with cross-resistance to epirubicin, but
      only MDARES showed cross-resistance to oxaliplatin. In conclusion, Pgp was
      identified as a key mediator of resistance to low docetaxel concentrations with
      other resistance mechanisms prominent at higher docetaxel concentrations.
      Supporting Pgp upregulation as one major mechanism of taxane resistance and cell
      line-specific alterations as another, both MCF7RES and MDARES were cross
      resistant to epirubicin (Pgp substrate), but only MDARES was cross-resistant to
      oxaliplatin (non-Pgp substrate).

PMID- 25596704
TI  - Overexpression of NKX6.1 is closely associated with progressive features and
      predicts unfavorable prognosis in human primary hepatocellular carcinoma.
AB  - The homeobox gene NKX6.1 was recently identified in cervical tumors. This study
      was designed to explore the clinical and prognostic significance of NKX6.1
      further in patients with primary hepatocellular carcinoma (HCC). The expression
      levels of NKX6.1 were examined using real-time PCR, Western blotting, and
      immunohistochemistry in HCC cell lines and HCC tissues. The invasion capability
      of cell lines following silencing or overexpression of NKX6.1 was investigated by
      Transwell assay. Cells proliferation was tested by MTT assays. Epithelial
      mesenchymal transition (EMT) marker expression levels were detected in relation
      to NKX6.1 expression. Correlation between NKX6.1 immunohistochemical staining,
      clinicopathologic parameters, and follow-up data of HCC patients was analyzed
      statistically. NKX6.1 expression was higher in HCC tissues compared to the
      adjacent noncancerous tissue. NKX6.1 overexpression was significantly correlated
      with tumor size, tumor differentiation, clinical stage, metastasis, and relapse.
      Kaplan-Meier analysis revealed that NKX6.1 overexpression was related to
      unfavorable 5-year disease-free survival and overall survival. Importantly,
      multivariate analysis indicated that NKX6.1 overexpression was an independent
      unfavorable marker for overall survival. Moreover, a significant relationship was
      observed between NKX6.1 and EMT marker expression levels, and NKX6.1 knockdown
      inhibited cell invasion, and overexpression of NKX6.1 promotes cell proliferation
      in vitro. NKX6.1 is upregulated in HCC and is a reliable prognostic marker for
      patients with HCC.

PMID- 25596705
TI  - Decreased expression of microRNA-107 predicts poorer prognosis in glioma.
AB  - The expression level of microRNA-107 (miR-107) has been proved to be decreased in
      many human malignant cancers. Especially in glioma, accumulating evidence
      indicates that miR-107 may play important parts in cell proliferation, apoptosis,
      and invasion in glioma. However, its clinical significance in glioma has not been
      investigated. This study aims at investigating the relationship between miR-107
      expression level and clinical significance and analyzing its value of miR-107 in
      valuing the prognosis of glioma patients. Quantitative real-time polymerase chain
      reaction (qRT-PCR) was used to measure the expression of miR-107 in 80 glioma and
      17 normal brain tissues. The results showed the miR-107 expression level in
      glioma tissues was significantly lower than those in normal brain tissues (p <
      0.001). The decreased expression of miR-107 in glioma was positively associated
      with high WHO grade (p < 0.001), low Karnofsky performance score (KPS) (p <
      0.001), and large tumor size (p < 0.001) and had a significant impact on overall
      survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001)
      according to Kaplan-Meier survival with log-rank test. Finally, Cox regression
      analyses showed that low miR-107 expression (p < 0.001) might be an independent
      prognostic parameter to predict poor prognosis. In conclusion, it is the first
      data to prove that expression level of miR-107 may be a novel and valuable
      prognostic factor in glioma.

PMID- 25596708
TI  - [The supply of experimental drugs in a clinical trial: who should pay?].

PMID- 25596707
TI  - MicroRNA-10b and minichromosome maintenance complex component 5 gene as
      prognostic biomarkers in breast cancer.
AB  - The aim of this study is to identify micro-ribonucleic acid (microRNA) and its
      target, in addition to their relationship to the outcome in breast cancer (BC).
      To achieve this aim, we investigated microRNA-10b (miR-10b) and minichromosome
      maintenance complex component 5 (MCM5 mRNA) expression in 230 breast tissue
      samples by real-time PCR and semiquantitative conventional RT-PCR, respectively.
      Relapse-free survival (RFS) associated with miRNA-10b and MCM5 mRNA were tested
      by Kaplan-Meier survival analysis. The impact of miRNA-10b andMCM5 mRNA
      expression on the survival was evaluated by Cox proportional hazard regression
      model. The expression of miRNA-10b and MCM5 mRNA was positive in 86.4 and 79.7 %
      breast cancer patients, respectively. The overall concordance rate between miRNA
      10b and MCM5 RNA was 90.4 %. The median follow-up period was 50 months. The
      survival analysis showed that high levels of both miR-10b and MCM5 were
      associated with short relapse free survival of BC. We identified MCM5 mRNA
      expression changes consistent with the miRNA-10b target regulation. Thus, we
      could consider miRNA-10b and MCM5 mRNA as prognostic markers and potential
      therapeutic targets in breast cancer to be applied to other patient data sets.

PMID- 25596710
TI  - The laboratory profile in idiopathic intracranial hypertension.
AB  - While overweight and female gender play an undisputable role in the pathogenesis
      of idiopathic intracranial hypertension (IIH), the contribution of other factors
      is still unclear. We have evaluated the laboratory findings of patients with IIH
      in an attempt to find the influence of abnormalities on the disease course.
      Included were 82 females after menarche and males older than 18 years who were
      followed up for at least 1 year. A wide range of laboratory parameters were
      examined at the time of presentation. The most frequent abnormal laboratory
      findings were elevated C reactive protein (CRP) (51 %), thrombophilia (31 %),
      increased plasma cortisol levels (29 %) and elevated lactate dehydrogenase (LDH)
      (20 %). Patients with elevated CRP and patients with thrombophilia had an
      unfavorable visual outcome. Increased cortisol levels and abnormal calcium
      correlated with a higher rate of recurrence. The visual outcome of patients with
      elevated LDH was better than those with normal LDH. It seems that certain
      metabolic, inflammatory and coagulation abnormalities may influence the course of
      IIH. If confirmed in further studies, these findings could contribute to
      elucidation of the etiology and prognosis of IIH.

PMID- 25596711
TI  - Pitfall in neurology: giant cell arteritis mimicking ocular myasthenia gravis.

PMID- 25596709
TI  - Human biomonitoring of aluminium after a single, controlled manual metal arc
      inert gas welding process of an aluminium-containing worksheet in nonwelders.
AB  - PURPOSE: Several existing field studies evaluate aluminium welding works but no
      thoroughly controlled exposure scenario for welding fume has been described yet.
      This study provides information about the uptake and elimination of aluminium
      from welding fumes under controlled conditions. METHODS: In the Aachen Workplace
      Simulation Laboratory, we are able to generate welding fumes of a defined
      particle mass concentration. We exposed 12, until then occupationally unexposed
      participants with aluminium-containing welding fumes of a metal inert gas (MIG)
      welding process of a total dust mass concentration of 2.5 mg/m(3) for 6 h. Room
      air filter samples were collected, and the aluminium concentration in air
      derived. Urine and plasma samples were collected directly before and after the 6
      h lasting exposure, as well as after 1 and 7 days. Human biomonitoring methods
      were used to determine the aluminium content of the samples with high-resolution
      continuum source atomic absorption spectrometry. RESULTS: Urinary aluminium
      concentrations showed significant changes after exposure compared to preexposure
      levels (mean t(1) (0 h) 13.5 ug/L; mean t(2) (6 h) 23.5 ug/L). Plasma results
      showed the same pattern but pre-post comparison did not reach significance.
      CONCLUSIONS: We were able to detect a significant increase of the internal
      aluminium burden of a single MIG aluminium welding process in urine, while plasma
      failed significance. Biphasic elimination kinetic can be observed. The German BAT
      of 60 ug/g creatinine was not exceeded, and urinary aluminium returned nearly to
      baseline concentrations after 7 days.

PMID- 25596712
TI  - Redefining a diagnosis: from meningeal plasma cell granuloma to rheumatoid
      meningitis. Report of a patient follow-up.

PMID- 25596713
TI  - The readability of the English Wikipedia article on Parkinson's disease.

PMID- 25596715
TI  - Author response to "scientific rigour is far more than a matter of sample size".

PMID- 25596716
TI  - Recent advances in image-guided targeted prostate biopsy.
AB  - Prostate cancer is a common malignancy in the United States that results in over
      30,000 deaths per year. The current state of prostate cancer diagnosis, based on
      PSA screening and sextant biopsy, has been criticized for both overdiagnosis of
      low-grade tumors and underdiagnosis of clinically significant prostate cancers
      (Gleason score >=7). Recently, image guidance has been added to perform targeted
      biopsies of lesions detected on multi-parametric magnetic resonance imaging
      (mpMRI) scans. These methods have improved the ability to detect clinically
      significant cancer, while reducing the diagnosis of low-grade tumors. Several
      approaches have been explored to improve the accuracy of image-guided targeted
      prostate biopsy, including in-bore MRI-guided, cognitive fusion, and
      MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent
      advances in these image-guided targeted prostate biopsy techniques. 

PMID- 25596714
TI  - Curcumin inhibits LPA-induced invasion by attenuating RhoA/ROCK/MMPs pathway in
      MCF7 breast cancer cells.
AB  - Breast cancer generally shows poor prognosis because of its invasion and
      metastasis. Lysophosphatidic acid (LPA) induces and aggravates cancer invasion
      and metastasis by activating its downstream signal pathways. RhoA/ROCK/MMP
      signaling was found one of the LPA-induced pathways, which may be involved in
      invasion of breast cancer. Furthermore, we investigated whether this pathway was
      involved in curcumin's effect against LPA-induced invasion. LPA incubation was
      used to enhance invasion of MCF-7 breast cancer cells. RhoA expression was
      knocked-down by siRNA technique. MTT assay was used to evaluate the
      proliferation. Transwell assay was utilized to investigate the invasion ability
      of MCF-7 cells. Real-time PCR and Western blotting were used to assess the
      expressions of RhoA, ROCK1, ROCK2, MMP2 and MMP9 at both translational and
      transcriptional levels. The RhoA and ROCK activities were also evaluated. LPA
      incubation significantly boosted invasion rate of MCF-7. RhoA silencing by siRNA
      dramatically inhibited LPA-enhanced invasion. Concurrently, RhoA and ROCK
      activities and expression levels of RhoA, ROCK1, ROCK2, MMP2 and MMP9 were down
      regulated by RhoA siRNA transfection. In order to avoid influence of cytotoxicity
      of curcumin, concentrations below 45 MUmol/L were selected to further investigate
      the mechanism of curcumin's anti-invasion effect. Invasion of LPA-incubated MCF-7
      cells was impaired by curcumin in a concentration-dependent manner. Concurrently,
      RhoA and ROCK activities and expression levels of RhoA, ROCK1, ROCK2, MMP2 and
      MMP9 were down-regulated by curcumin in a concentration-dependent manner. In
      conclusion, RhoA/ROCK/MMPs pathway activation is involved in LPA-induced invasion
      in MCF-7 cells; curcumin inhibited LPA-induced invasion in MCF-7 cells by
      attenuating RhoA/ROCK/MMPs pathway. 

PMID- 25596717
TI  - Evaluation of a dansyl-based amino acid DNSBA as an imaging probe for apoptosis
      detection.
AB  - Imaging agents that enable direct detection of apoptosis are highly desirable in
      the field of monitoring chemotherapeutic response as well as early diagnosis and
      disease monitoring. Previous work demonstrated that the dansyled amino acid DNSBA
      is used to specifically and selectively detect apoptotic cancer cells at the both
      early and late stages, but the mechanism remains unclear. In this work, we
      evaluated DNSBA as a tool for monitoring cell apoptosis in CNE1 tumor cell models
      both in vitro and ex vivo after its in vivo administration, which was confirmed
      by other assays. The ability of DNSBA to detect multiple pathways and different
      stages of apoptosis leading to cell death may be advantageous in the evaluation
      of cancer treatment indicative of a positive therapeutic outcome. The uptake
      change of molecular probes DNSBA in CNE1 cells represented the changes of
      apoptotic rate in a caspase-dependent manner. However, the accumulation of DNSBA
      in apoptotic cells did not increase with the enhanced membrane permeability.
      Furthermore, ex vivo study demonstrated DNSBA has a similar pattern as the TUNEL
      positive cells. In conclusion, DNSBA cellular imaging is useful for the early
      assessment of treatment-induced apoptosis, and thus may act as a substitute for
      Annexin V for assessing treatment response. 

PMID- 25596718
TI  - Functional, morphological, and apoptotic alterations in skeletal muscle of ARC
      deficient mice.
AB  - Apoptotic signaling plays an important role in the development and maintenance of
      healthy skeletal muscle. However, dysregulation of apoptotic signals in skeletal
      muscle is associated with atrophy and loss of function. Apoptosis repressor with
      caspase recruitment domain (ARC) is a potent anti-apoptotic protein that is
      highly expressed in skeletal muscle; however, its role in this tissue has yet to
      be elucidated. To investigate whether ARC deficiency has morphological,
      functional, and apoptotic consequences, skeletal muscle from 18 week-old wild
      type and ARC knockout (KO) mice was studied. In red muscle (soleus), we found
      lower maximum tetanic force, as well as a shift towards a greater proportion of
      type II fibers in ARC KO mice. Furthermore, the soleus of ARC KO mice exhibited
      lower total, as well as fiber type-specific cross sectional area in type I and
      IIA fibers. Interestingly, these changes in ARC KO mice corresponded with
      increased DNA fragmentation, albeit independent of caspase or calpain activation.
      However, cytosolic fractions of red muscle from ARC KO mice had higher apoptosis
      inducing factor content, suggesting increased mitochondrial-mediated, caspase
      independent apoptotic signaling. This was confirmed in isolated mitochondrial
      preparations, as mitochondria from skeletal muscle of ARC KO mice were more
      susceptible to calcium stress. Interestingly, white muscle from ARC KO mice
      showed no signs of altered apoptotic signaling or detrimental morphological
      differences. Results from this study suggest that even under basal conditions ARC
      influences muscle apoptotic signaling, phenotype, and function, particularly in
      slow and/or oxidative muscle.

PMID- 25596720
TI  - Diabetes mellitus, and not obesity, is associated with lower survival following
      liver transplantation.
AB  - BACKGROUND AND AIMS: The impact of obesity on survival following liver
      transplantation is unclear, and existing studies report conflicting results. Our
      current study aims to further delineate the impact of obesity using population
      based registry data from the USA. METHODS: All US adult liver transplant
      recipients from 2003 to 2012 were evaluated using the United Network for Organ
      Sharing registry. The impact of obesity on survival following liver
      transplantation was further stratified into class I obesity [body mass index
      (BMI) 30.0-34.9 kg/m(2)], class II obesity (BMI 35.0-39.9 kg/m(2)), and class III
      obesity (BMI >= 40 kg/m(2)) and evaluated using Kaplan-Meier methods and
      multivariate Cox proportional hazards models. RESULTS: Overall, 57,255 patients
      with chronic liver disease underwent liver transplantation, among which 32.9 %
      had BMI >= 30 kg/m(2). While patients in all obesity classes had similar survival
      to patients with BMI 18.0-24.9 kg/m(2), the presence of concurrent diabetes
      mellitus resulted in significantly lower post-transplant survival. After
      multivariate regression, post-transplant survival in patients with class II
      obesity (HR 0.97; 95 % CI 0.89-1.05) or class III obesity (HR 0.99; 95 % CI 0.90
      1.09) was not significantly lower than patients with BMI 18.0-24.9 kg/m(2), but
      diabetes mellitus was independently associated with lower post-transplant
      survival (HR 1.29; 95 % CI 1.21-1.36). CONCLUSION: In conclusion, obesity alone
      was not associated with lower post-transplant survival. However, DM, either alone
      or comorbid with obesity, is associated with significantly greater post
      transplant mortality.

PMID- 25596719
TI  - Colorectal cancer screening and prevention in women.
AB  - Colorectal cancer (CRC) is one of the leading cancers and cause of cancer deaths
      in American women and men. Females and males share a similar lifetime cumulative
      risk of CRC however, substantial differences in risk factors, tumor biology, and
      effectiveness of cancer prevention services have been observed between them. This
      review distills the evidence documenting the unique variation observed between
      the genders relating to CRC risk factors, screening and prevention. Consistent
      evidence throughout the world demonstrates that women reach equivalent levels of
      adenomas and CRC as men but it occurs nearly a decade later in life than in their
      male counterparts. Women have a higher proportion of tumors which are
      hypermethylated, have microsatellite instability and located in the proximal
      colon suggesting the serrated pathway may be of greater consequence in them than
      in men. Other CRC risk factors such as smoking, diet and obesity have been shown
      to have disparate effects on women which may related to interactions between
      estrogen exposure, body fat distribution, and the biologic underpinnings of their
      tumors. There is data showing the uptake, choice, and efficacy of different CRC
      screening methods in women is dissimilar to that in men. The mortality benefit
      from FOBT, sigmoidoscopy, and protection from interval CRC by colonoscopy appears
      to be lower in women than men. A greater understanding of these gender
      idiosyncrasies will facilitate an personalized approach to CRC prevention and
      should ultimately lead to a reduced burden of disease. 

PMID- 25596721
TI  - FK506-Binding Protein 5 mRNA Levels in Ileal Mucosa Are Associated with Pouchitis
      in Patients with Ulcerative Colitis.
AB  - BACKGROUND: Although the pathogenesis of pouchitis is incompletely understood,
      steroid and FK506 therapy are significantly associated with pouchitis. These
      medical treatments are regulated by the FK506-binding protein (FKBP) 4 and FKBP5
      genes. AIM: This study aimed to evaluate the relationship between pouchitis and
      FKBP4 and FKBP5 mRNA expression in ileal mucosa at the time of colectomy.
      METHODS: Ileal mucosa specimens were collected from 71 patients who underwent
      ileal pouch-anal anastomosis for ulcerative colitis. FKBP4 and FKBP5 mRNA
      expression was evaluated. The relationship between mRNA expression and
      clinicopathological factors, including developed pouchitis, was investigated.
      RESULTS: Of these 71 patients, 25 (35.2 %) patients developed pouchitis in a mean
      duration of 20.2 months (range 0-68 months). FKBP4 mRNA levels in patients who
      received an immunomodulator were significantly higher than those in untreated
      patients (0.167 +/- 0.060 vs 0.131 +/- 0.065, p = 0.009). However, FKBP5 mRNA
      levels in patients who received a three-stage operation were significantly lower
      than those in the other patients (1.97 +/- 1.15 vs 2.70 +/- 1.12, p = 0.02). A
      total dose of prednisolone >9.4 g (HR 2.84, p = 0.02) before colectomy and FKBP5
      mRNA level higher than the median (HR 4.49, p = 0.01) were identified as factors
      related to pouchitis. CONCLUSIONS: FKBP5 mRNA levels in ileal mucosa at the time
      of colectomy are significantly associated with pouchitis and may be a predictive
      factor for developing pouchitis.

PMID- 25596723
TI  - Knowledge of ovarian reserve and reproductive choices.
AB  - OBJECTIVE: To determine the factors that influence the reproductive choices of
      health care professionals, and to assess whether knowledge of ovarian reserve
      would modify those choices. METHOD: A cross-sectional survey utilizing anonymous
      questionnaires that assessed demographics, knowledge, attitudes and choices of
      female and male health care professionals between the ages of 20-55 (N = 185) who
      work at an academic medical center RESULT(S): Of the 185 respondents, 75% were
      female, 35% were residents and 35% were married. Among those who were delaying
      childbearing 39% wanted to complete their education, 25% had no identified
      partner, 10% were too active professionally and 4% could not afford children at
      the time. If testing of the individual or individual's partner indicated
      diminished ovarian reserve, 48% of those responding would try to have a child
      sooner, 21% would opt for oocyte cryopreservation, 7% would try to find a partner
      sooner, 7% would pursue adoption, and 3% would select embryo cryopreservation.
      Only 14% would not actively pursue treatment or make lifestyle changes. These
      results varied significantly with marital status but did not differ between
      participants with and without children. Similarly, choices did not vary
      significantly with religious belief or ethnicity. CONCLUSION(S): Increased
      information about a woman's reproductive reserve would lead individuals to modify
      life choices. Physicians caring for reproductive-age women and men should inquire
      about their childbearing plans, and educate those who are postponing childbearing
      regarding the normal pattern of reproductive decline.

PMID- 25596722
TI  - Immuno-affinity purification of PglPGIP1, a polygalacturonase-inhibitor protein
      from pearl millet: studies on its inhibition of fungal polygalacturonases and
      role in resistance against the downy mildew pathogen.
AB  - Polygalacturonase-inhibitor proteins (PGIPs) are important plant defense proteins
      which modulate the activity of microbial polygalacturonases (PGs) leading to
      elicitor accumulation. Very few studies have been carried out towards
      understanding the role of PGIPs in monocot host defense. Hence, present study was
      taken up to characterize a native PGIP from pearl millet and understand its role
      in resistance against downy mildew. A native glycosylated PGIP (PglPGIP1) of ~43
      kDa and pI 5.9 was immunopurified from pearl millet. Comparative inhibition
      studies involving PglPGIP1 and its non-glycosylated form (rPglPGIP1; recombinant
      pearl millet PGIP produced in Escherichia coli) against two PGs, PG-II isoform
      from Aspergillus niger (AnPGII) and PG-III isoform from Fusarium moniliforme,
      showed both PGIPs to inhibit only AnPGII. The protein glycosylation was found to
      impact only the pH and temperature stability of PGIP, with the native form
      showing relatively higher stability to pH and temperature changes. Temporal
      accumulation of both PglPGIP1 protein (western blot and ELISA) and transcripts
      (real time PCR) in resistant and susceptible pearl millet cultivars showed
      significant Sclerospora graminicola-induced accumulation only in the incompatible
      interaction. Further, confocal PGIP immunolocalization results showed a very
      intense immuno-decoration with highest fluorescent intensities observed at the
      outer epidermal layer and vascular bundles in resistant cultivar only. This is
      the first native PGIP isolated from millets and the results indicate a role for
      PglPGIP1 in host defense. This could further be exploited in devising pearl
      millet cultivars with better pathogen resistance.

PMID- 25596724
TI  - Silent ischemic brain lesions after transcatheter aortic valve replacement:
      lesion distribution and predictors.
AB  - AIMS: Silent ischemic brain lesions and ischemic stroke are known complications
      of transcatheter aortic valve replacement (TAVR). We aimed to investigate the
      occurrence and distribution of TAVR-related silent ischemic brain lesions using
      diffusion-weighted magnetic resonance imaging (DWI). METHODS: Consecutive
      patients with severe aortic valve stenosis treated with TAVR underwent cerebral
      DWI within 5 days after the index procedure. DWI scans were analyzed for the
      occurrence and distribution of new ischemic lesions post-TAVR. RESULTS: Forty-two
      patients were enrolled in this study. After TAVR, a total of 276 new cerebral
      ischemic lesions were detected in 38 (90 %) patients, with a median of 4.5
      (interquartile range 2.0-7.0) lesions per patient. A total of 129 (47 %) lesions
      were detected in the cortical regions, 97 (35 %) in the subcortical regions, and
      50 (18 %) in the cerebellum or brainstem. The median lesion volume was 20.2 ul
      (10.0, 42.7) and the total ischemic lesion volume was 132.3 ul (42.8, 336.9). The
      new ischemic brain lesions were clinically silent in 37 (97 %) patients; the
      other patient had a transient ischemic attack. Age (B = 0.528, p = 0.015),
      hyperlipidaemia (B = 5.809, p = 0.028) and post-dilatation of the implanted
      prosthesis (B = 7.196, p = 0.029) were independently associated with the number
      of post-TAVR cerebral DWI lesions. In addition, peak transaortic gradient was
      independently associated with post-procedural total infarct volume. CONCLUSION:
      Clinically silent cerebral infarcts occurred in 90 % of patients following TAVR,
      most of which were small (<20 MUl) and located in the cortical regions of the
      cerebral hemispheres. An independent association was found between age,
      hyperlipidaemia and balloon post-dilatation and the number of post-TAVR ischemic
      brain lesions. Only peak transaortic gradient was independently associated with
      post-procedural total infarct volume.

PMID- 25596725
TI  - Renal sympathetic denervation for treatment of ventricular arrhythmias: a review
      on current experimental and clinical findings.
AB  - Ventricular arrhythmias (VAs) remain the major cause of mortality and sudden
      cardiac death (SCD) in almost all forms of heart disease. Despite so many
      therapeutic advances, such as pharmacological therapies, catheter ablation, and
      arrhythmia surgery, management of VAs remains a great challenge for
      cardiologists. Evidence from histological studies and from direct nerve activity
      recordings have suggested that increased sympathetic nerve density and activity
      contribute to the generation of VAs and SCD. It is well known that renal
      sympathetic nerve (RSN), either afferent component or efferent component, plays
      an important role in modulation of central sympathetic activity. We have recently
      shown that RSN activation by electrical stimulation significantly increases
      cardiac and systemic sympathetic activity and promotes the incidence of acute
      ischemia-induced VAs, suggesting RSN has a role in the development of VAs.
      Initial experience of RSN denervation (RDN) in patients with resistant
      hypertension showed that this novel and minimally invasive device-based approach
      significantly reduced not only kidney but also whole-body norepinephrine
      spillover. In addition, experimental studies find that left stellate ganglion
      nerve activity is significantly decreased after RDN. Based on these observations,
      it is reasonable to conclude that RDN may be an effective therapy for the
      management of VAs. Indeed, RDN has provided a protection against VAs in both
      animal models and patients. In this article, we review the role of the RSN in the
      generation of VAs and SCD and the role of RDN as a potential treatment strategy
      for VAs and SCD. 

PMID- 25596726
TI  - Evidence of an association between sleep and levodopa-induced dyskinesia in an
      animal model of Parkinson's disease.
AB  - Levodopa-induced dyskinesia (LID) represents a major challenge for clinicians
      treating patients affected by Parkinson's disease (PD). Although levodopa is the
      most effective treatment for PD, the remodeling effects induced by disease
      progression and the pharmacologic treatment itself cause a narrowing of the
      therapeutic window because of the development of LID. Although animal models of
      PD provide strong evidence that striatal plasticity underlies the development of
      dyskinetic movements, the pathogenesis of LID is not entirely understood. In
      recent years, slow homeostatic adjustment of intrinsic excitability occurring
      during sleep has been considered fundamental for network stabilization by
      gradually modifying plasticity thresholds. So far, how sleep affects on LID has
      not been investigated. Therefore, we measured synaptic downscaling across sleep
      episodes in a parkinsonian animal model showing dyskinetic movements similar to
      LID. Our electrophysiological, molecular, and behavioral results are consistent
      with an impaired synaptic homeostasis during sleep in animals showing dyskinesia.
      Accordingly, sleep deprivation causes an anticipation and worsening of LID
      supporting a link between sleep and the development of LID. 

PMID- 25596727
TI  - In vitro study of calcium hydroxide removal from mandibular molar root canals.
AB  - INTRODUCTION: Previous studies have shown the difficulty in removing calcium
      hydroxide (Ca[OH]2) paste from the root canals before root filling. METHODS:
      Mesial and distal canals of 30 mandibular molars were prepared with the WaveOne
      Primary (25/.08) and Large file (40/.08) (Dentsply Tulsa Dental Specialties,
      Tulsa, OK), respectively. All canals were then filled with Ca(OH)2. The teeth
      were divided into the following 3 treatment groups (each with n = 10): (1)
      instrumentation with needle irrigation, (2) instrumentation with irrigation and
      passive ultrasonic activation (PUI), and (3) the GentleWave system (Sonendo, Inc,
      Laguna Hills, CA) without instrumentation. The irrigation time in each group was
      7.5 minutes. To further test the efficiency of the GentleWave system, shorter
      times of 90 seconds were tested using water alone. Reconstructed micro-computed
      tomographic scans were used to measure the volume of the canals and Ca(OH)2 after
      instrumentation, initial filling of Ca(OH)2, and after its removal. The
      percentage of Ca(OH)2 remaining in the canals was calculated. RESULTS: None of
      the 10 teeth (30 canals) in the conventional irrigation and PUI groups were
      completely cleaned of Ca(OH)2 in 7.5 minutes. In the apical third of mesial and
      distal canals, respectively, conventional irrigation removed 47.82% +/- 16.36%
      and 77.68% +/- 12.82%, PUI removed 61.66% +/- 25.54% and 88.85 +/- 12.06%, and
      the GentleWave system removed significantly more Ca(OH)2 (P < .05) with 100% and
      98.78% +/- 3.84%. Additional experiments in 10 teeth, using only water as the
      irrigant, revealed that the GentleWave system removed 99.85% and 99.97% of
      Ca(OH)2 within 90 seconds without the use of any instruments in the mesial and
      distal canals, respectively. CONCLUSIONS: The study confirms the difficulty to
      remove Ca(OH)2 from root canals using conventional methods. The GentleWave system
      removed the paste within 90 seconds using water irrigation alone.

PMID- 25596728
TI  - Healing after root-end microsurgery by using mineral trioxide aggregate and a new
      calcium silicate-based bioceramic material as root-end filling materials in dogs.
AB  - INTRODUCTION: The purpose of this study was to compare healing after root-end
      surgery by using grey mineral trioxide aggregate (MTA) and EndoSequence Root
      Repair Material (RRM) as root-end filling material in an animal model. METHODS:
      Apical periodontitis was induced in 55 mandibular premolars of 4 healthy beagle
      dogs. After 6 weeks, root-end surgeries were performed by using modern
      microsurgical techniques. Two different root-end filling materials were used,
      grey MTA and RRM. Six months after surgery, healing of the periapical area was
      assessed by periapical radiographs, cone-beam computed tomography (CBCT), micro
      computed tomography (CT), and histology. RESULTS: Minimal or no inflammatory
      response was observed in the majority of periapical areas regardless of the
      material. The degree of inflammatory infiltration and cortical plate healing were
      not significantly different between the 2 materials. However, a significantly
      greater root-end surface area was covered by cementum-like, periodontal ligament
      like tissue, and bone in RRM group than in MTA group. When evaluating with
      periapical radiographs, complete healing rate in RRM and MTA groups was 92.6% and
      75%, respectively, and the difference was not statistically significant (P =
      .073). However, on CBCT and micro CT images, RRM group demonstrated significantly
      superior healing on the resected root-end surface and in the periapical area (P =
      .000 to .027). CONCLUSIONS: Like MTA, RRM is a biocompatible material with good
      sealing ability. However, in this animal model RRM achieved a better tissue
      healing response adjacent to the resected root-end surface histologically. The
      superior healing tendency associated with RRM could be detected by CBCT and micro
      CT but not periapical radiography.

PMID- 25596729
TI  - Management of Propionibacterium acnes infection after shoulder surgery.
AB  - Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus commonly
      isolated from the flora of the face, chest, and axilla region. It has emerged as
      a major pathogen responsible for postoperative shoulder infections after both
      arthroscopy and arthroplasty procedures. Patients with P. acnes shoulder
      infection typically present with normal laboratory values (white blood cells
      (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)) making
      diagnosis difficult. Several intraoperative tissue cultures should be obtained
      and cultured in both agar plate and broth in aerobic and anaerobic conditions for
      a minimum of 13 days to optimize the sensitivity and specificity to detect P.
      acnes. The utilization of intraoperative frozen sections to detect P. acnes
      infection is not reliable. Risk factors include male, cloudy synovial fluid,
      lucencies around the implant, and periprosthetic membrane formation. Managements
      include irrigation and debridement, single or two-staged revision, and
      intravenous antibiotics. Open biopsy prior to the final implantation (two-staged
      revision) may help detect persistent P. acnes infection. Penicillin and
      cephalosporins are effective against clinical P. acnes infection and biofilm in
      vitro. Combination antibiotic therapy with rifampin and daptomycin may further
      increase the clinical efficacy of treatment. 

PMID- 25596730
TI  - Up-regulation of CDK9 kinase activity and Mcl-1 stability contributes to the
      acquired resistance to cyclin-dependent kinase inhibitors in leukemia.
AB  - Flavopiridol is a small molecule inhibitor of cyclin-dependent kinases (CDK)
      known to impair global transcription via inactivation of positive transcription
      elongation factor b. It has been demonstrated to have significant activity
      predominantly in chronic lymphocytic leukemia and acute myeloid leukemia in phase
      I/II clinical trials while other similar CDK inhibitors are vigorously being
      pursued in pre-clinical and clinical studies. Although flavopiridol is a potent
      therapeutic agent against blood diseases, some patients still have primary or
      acquired resistance throughout their clinical course. Considering the limited
      knowledge of resistance mechanisms of flavopiridol, we investigated the potential
      mechanisms of resistance to flavopiridol in a cell line system, which gradually
      acquired resistance to flavopiridol in vitro, and then confirmed the mechanism in
      patient samples. Herein, we present that this resistant cell line developed
      resistance through up-regulation of phosphorylation of RNA polymerase II C
      terminal domain, activation of CDK9 kinase activity, and prolonged Mcl-1
      stability to counter flavopiridol's drug actions. Further analyses suggest
      MAPK/ERK activation-mediated Mcl-1 stabilization contributes to the resistance
      and knockdown of Mcl-1 in part restores sensitivity to flavopiridol-induced
      cytotoxicity. Altogether, these findings demonstrate that CDK9 is the most
      relevant target of flavopiridol and provide avenues to improve the therapeutic
      strategies in blood malignancies. 

PMID- 25596731
TI  - c-myc copy number gain is a powerful prognosticator of disease outcome in
      cervical dysplasia.
AB  - Cervical carcinoma develops from preneoplasia by a multistep process. Although
      most low-grade dysplastic lesions will regress without intervention and even high
      grade changes exhibit a substantial rate of regression, a small percentage of
      dysplasia will progress over time. Thus, indicators are needed to estimate the
      biological risk and to help avoid overtreatment in women who desire to preserve
      fertility. In addition to the classical biomarkers, PCR-ELISA-determined HPV
      genotype and immunohistochemically assessed p16INK4a and Ki-67 expression, cells
      with integrated HPV and copy number gain of TERC and c-myc were quantified in a
      panel of 104 benign, intraepithelial neoplastic (CIN I, II, III) and cancerous
      lesions using fluorescence in situ hybridization. Optimal cut-off values were
      calculated; Kaplan-Meier curves and a Cox proportional hazard regression model
      were used to evaluate prognostic signatures. The assay reliably identified HPV
      integration, TERC and c-myc copy number gain as determined by comparisons with
      established biomarkers. All biomarker levels increased with the progression of
      the disease. However, only c-myc copy number gain independently prognosticated a
      low probability of dysplastic regression. Our results suggest that c-myc plays a
      key role in the process of dysplastic transformation and might thus be exploited
      for treatment and follow-up decision-making of cervical dysplasia. 

PMID- 25596732
TI  - Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic
      and pro-invasive myofibroblasts.
AB  - Stromal fibroblasts become altered in response to solid cancers, to exhibit
      myofibroblastic characteristics, with disease promoting influence. Infiltrating
      mesenchymal stem cells (MSC) may contribute towards these changes, but the
      factors secreted by cancer cells that impact MSC differentiation are poorly
      understood. We investigated the role of nano-metre sized vesicles (exosomes),
      secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM
      MSC), and the subsequent functional consequences of such changes. Purified
      exosomes impaired classical adipogenic differentiation, skewing differentiation
      towards alpha-smooth muscle actin (alphaSMA) positive myofibroblastic cells. A
      single exosomes treatment generated myofibroblasts secreting high levels of VEGF
      A, HGF and matrix regulating factors (MMP-1, -3 and -13). Differentiated MSC had
      pro-angiogenic functions and enhanced tumour proliferation and invasivity
      assessed in a 3D co-culture model. Differentiation was dependent on exosomal
      TGFbeta, but soluble TGFbeta at matched dose could not generate the same
      phenotype. Exosomes present in the cancer cell secretome were the principal
      factors driving this phenotype. Prostate cancer exosomes dominantly dictate a
      programme of MSC differentiation generating myofibroblasts with functional
      properties consistent with disease promotion. 

PMID- 25596733
TI  - SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B
      ubiquitination.
AB  - Aberrant elevation of JARID1B and histone H3 lysine 4 trimethylation (H3K4me3) is
      frequently observed in many diseases including prostate cancer (PCa), yet the
      mechanisms on the regulation of JARID1B and H3K4me3 through epigenetic
      alterations still remain poorly understood. Here we report that Skp2 modulates
      JARID1B and H3K4me3 levels in vitro in cultured cells and in vivo in mouse
      models. We demonstrated that Skp2 inactivation decreased H3K4me3 levels, along
      with a reduction of cell growth, cell migration and malignant transformation of
      Pten/Trp53 double null MEFs, and further restrained prostate tumorigenesis of
      Pten/Trp53 mutant mice. Mechanistically, Skp2 decreased the K63-linked
      ubiquitination of JARID1B by E3 ubiquitin ligase TRAF6, thus decreasing JARID1B
      demethylase activity and in turn increasing H3K4me3. In agreement, Skp2
      deficiency resulted in an increase of JARID1B ubiquitination and in turn a
      reduction of H3K4me3, and induced senescence through JARID1B accumulation in
      nucleoli of PCa cells and prostate tumors of mice. Furthermore, we showed that
      the elevations of Skp2 and H3K4me3 contributed to castration-resistant prostate
      cancer (CRPC) in mice, and were positively correlated in human PCa specimens.
      Taken together, our findings reveal a novel network of SKP2-JARID1B, and
      targeting SKP2 and JARID1B may be a potential strategy for PCa control. 

PMID- 25596734
TI  - The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA
      damage.
AB  - Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl
      (ABP) is a major human bladder carcinogen from tobacco smoke and other sources.
      In mice, male bladder is more susceptible to ABP-induced carcinogenesis than
      female bladder, but ABP is more carcinogenic in the livers of female mice than of
      male mice. Here, we show that castration causes male mice to acquire female
      phenotype regarding susceptibility of bladder and liver to ABP. However, spaying
      has little impact on organ susceptibility to ABP. Liver UDP
      glucuronosyltransferases (UGTs) are believed to protect liver against but
      sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally
      reduces their toxicity and promotes their elimination via urine, but the
      metabolites are labile in urine, delivering carcinogenic species to the bladder.
      Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice
      increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity
      is significantly higher in wild-type female mice than in their male counterparts,
      and castration also significantly increases ABP-specific UGT activity in the
      liver. Taken together, our data suggest that androgen increases bladder
      susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver
      enzyme, but exclude UGT as an important mediator. 

PMID- 25596735
TI  - Carnosic acid sensitized TRAIL-mediated apoptosis through down-regulation of c
      FLIP and Bcl-2 expression at the post translational levels and CHOP-dependent up
      regulation of DR5, Bim, and PUMA expression in human carcinoma caki cells.
AB  - Carnosic acid is a phenolic diterpene from rosmarinus officinalis, and has
      multiple functions, such as anti-inflammatory, anti-viral, and anti-tumor
      activity. In this study, we examined whether carnosic acid could sensitize TRAIL
      mediated apoptosis in human renal carcinoma Caki cells. We found that carnosic
      acid markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki,
      ACHN, and A498), and human hepatocellular carcinoma (SK-HEP-1), and human breast
      carcinoma (MDA-MB-231) cells, but not normal cells (TMCK-1 and HSF). Carnosic
      acid induced down-regulation of c-FLIP and Bcl-2 expression at the post
      translational levels, and the over-expression of c-FLIP and Bcl-2 markedly
      blocked carnosic acid-induced TRAIL sensitization. Furthermore, carnosic acid
      induced death receptor (DR)5, Bcl-2 interacting mediator of cell death (Bim), and
      p53 up-regulated modulator of apoptosis (PUMA) expression at the transcriptional
      levels via CCAAT/enhancer-binding protein-homologous protein (CHOP). Down
      regulation of CHOP expression by siRNA inhibited DR5, Bim, and PUMA expression,
      and attenuated carnosic acid plus TRAIL-induced apoptosis. Taken together, our
      study demonstrates that carnosic acid enhances sensitization against TRAIL
      mediated apoptosis through the down-regulation of c-FLIP and Bcl-2 expression,
      and up-regulation of ER stress-mediated DR5, Bim, and PUMA expression at the
      transcriptional levels. 

PMID- 25596736
TI  - P62 regulates resveratrol-mediated Fas/Cav-1 complex formation and transition
      from autophagy to apoptosis.
AB  - Resveratrol is a potential polyphenol drug used in cancer treatment. We examined
      the relationship between autophagy and apoptosis in RSV-treated non-small lung
      adenocarcinoma A549 cells. Resveratrol treatment increased autophagy and
      autophagy-mediated degradation of P62. Immunocytochemistry revealed P62 co
      localized with Fas/Cav-1 complexes, known to induce apoptosis. However, siRNA
      mediated P62 downregulation enhanced formation of Fas/Cav-1 complexes, suggesting
      that P62 inhibited Fas/Cav-1 complex formation. Fas/Cav-1 complexes triggered
      caspase-8 activation and cleavage of Beclin-1, releasing a C-terminal Beclin-1
      peptide that translocated to the mitochondria and initiate apoptosis. Inhibition
      of autophagy by siRNA-mediated repression of Beclin-1 also blocked RSV-induced
      apoptosis, showing a dependence of apoptosis on autophagy. P62 knockdown by siRNA
      accelerated the activation of caspase-8 and initiate apoptosis, while Cav-1
      knockdown inhibited apoptosis, but increased autophagy. Inhibition of autophagy
      by 3-MA prevented both P62 degradation and induction of apoptosis, whereas
      inhibition of apoptosis by z-IETD-FMK or z-DEVD-FMK enhanced both P62 induction
      and autophagic cell death. In conclusion, P62 links resveratrol-induced autophagy
      to apoptosis. P62 blocks apoptosis by inhibiting Fas/Cav-1 complex formation, but
      RSV-induced autophagic degradation of P62 enables formation of Fas/Cav-1
      complexes which then activate caspase-8-mediated Beclin-1 cleavage, resulting in
      translocation of the Beclin-1 C-terminal fragment to the mitochondria to initiate
      apoptosis. 

PMID- 25596737
TI  - Cytotoxic activity of the novel small molecule AKT inhibitor SC66 in
      hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is characterized by limited response to current
      drug therapies. Here, we report that SC66, a novel AKT inhibitor, reduced cell
      viability in a dose- and time-dependent manner, inhibited colony formation and
      induced apoptosis in HCC cells. SC66 treatment led to a reduction in total and
      phospho-AKT levels. This was associated with alterations in cytoskeleton
      organization, a reduction in expression levels of E-cadherin, beta-catenin and
      phospho-FAK, together with up-regulation of Snail protein levels. All these
      alterations were coupled with anoikis cell death induction. In addition, SC66
      induced the production of reactive oxygen species (ROS) and DNA damage. Pre
      treatment with the ROS scavenger N-Acetyl-cysteine (NAC) prevented SC66-induced
      cell growth inhibition and anoikis. SC66 significantly potentiated the effects of
      both conventional chemotherapeutic and targeted agents, doxorubicin and
      everolimus, respectively. In vivo, SC66 inhibited tumor growth of Hep3B cells in
      xenograft models, with a similar mechanism observed in the in vitro model. Taken
      together, these data indicate that the AKT inhibitor SC66 had antitumor effects
      on HCC cells. This was mediated by ROS production, induction of anoikis-mediated
      cell death and inhibition of the AKT cell survival pathway. Our results provide a
      rational basis for the use of SC66 in HCC treatment. 

PMID- 25596739
TI  - The PI3K inhibitor GDC-0941 displays promising in vitro and in vivo efficacy for
      targeted medulloblastoma therapy.
AB  - Deregulation of the Phosphoinositide 3-kinase (PI3K)/AKT signalling network is a
      hallmark of oncogenesis. Also medulloblastoma, the most common malignant brain
      tumor in children, is characterized by high levels of AKT phosphorylation and
      activated PI3K signalling in medulloblastoma is associated with enhanced cellular
      motility, survival and chemoresistency underscoring its role of as a potential
      therapeutic target. Here we demonstrate that GDC-0941, a highly specific PI3K
      inhibitor with good clinical tolerability and promising anti-neoplastic activity
      in adult cancer, also displays anti-proliferative and pro-apoptotic effects in
      pediatric human medulloblastoma cell lines. Loss in cell viability is accompanied
      by reduced phosphorylation of AKT, a downstream target of PI3K. Furthermore, we
      show that GDC-0941 attenuates the migratory capacity of medulloblastoma cells and
      targets subpopulations expressing the stem cell marker CD133. GDC-0941 also
      synergizes with the standard medulloblastoma chemotherapeutic etoposide. In an
      orthotopic xenograft model of the most aggressive human medulloblastoma variant
      we document that oral adminstration of GDC-0941 impairs tumor growth and
      significantly prolongs survival. These findings provide a rational to further
      investigate GDC-0941 alone and in combination with standard chemotherapeutics for
      medulloblastoma treatment. 

PMID- 25596738
TI  - CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma
      cells through parallel regulation of AKT and FGFR activities.
AB  - Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly
      recognized as key mediators of cell movement and cell differentiation during
      vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is
      overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in
      this setting remains unclear. Here, we find CRIPTO expression as especially high
      in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides
      cancer cell clones with mesenchymal traits. Experimental studies in PCa models
      showed that one notable function of CRIPTO expression in prostate carcinoma cells
      may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial
      mesenchymal transition and sustains a mesenchymal state. In the observed
      signaling events, FGFR1 appears to function parallel to AKT, and the two pathways
      act cooperatively to enhance migratory, invasive and transformation properties
      specifically in the CRIPTO overexpressing cells. Collectively, these findings
      suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in
      favor of the emergence of mesenchymal-like cancer cells during the development of
      aggressive prostate tumors. 

PMID- 25596740
TI  - miR-874 functions as a tumor suppressor by inhibiting angiogenesis through
      STAT3/VEGF-A pathway in gastric cancer.
AB  - MicroRNAs are endogenously expressed, small non-coding RNAs that regulate gene
      expression by targeting mRNAs for translational repression or degradation. Our
      previous studies indicated that miR-874 played a suppressive role in gastric
      cancer (GC) development and progression. However, the role of miR-874 in tumor
      angiogenesis and the mechanisms underlying its function in GC remained to be
      clarified. Here, gain- and loss-of-function assays demonstrated that miR-874
      inhibited the tumor angiogenesis of GC cells in vitro and in vivo. Through
      reporter gene and western blot assays, STAT3 was shown to be a direct target of
      miR-874. Overexpression of STAT3 rescued the loss of tumor angiogenesis caused by
      miR-874. Conversely, the STAT3-shRNA attenuated the increased tumor angiogenesis
      caused by the miR-874-inhibitor. Furthermore, the levels of miR-874 were
      inversely correlated with those of STAT3 protein in GC tissues. Taken together,
      these findings indicate that down-regulation of miR-874 contributes to tumor
      angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a
      target for human GC therapy. 

PMID- 25596741
TI  - Silencing of the tumor suppressor gene WNK2 is associated with upregulation of
      MMP2 and JNK in gliomas.
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade
      extracellular matrix (ECM), thus assisting invasion. Upregulation of MMPs,
      frequently reported in gliomas, is associated with aggressive behavior. WNK2 is a
      tumor suppressor gene expressed in normal brain, and silenced by promoter
      methylation in gliomas. Patients without WNK2 exhibited poor prognosis, and its
      downregulation was associated with increased glioma cell invasion. Here we showed
      that MMP2 expression and activity are increased in glioma cell lines that do not
      express WNK2. Also, WNK2 inhibited JNK, a process associated with decreasing
      levels of MMP2. Thus, WNK2 promoter methylation and silencing in gliomas is
      associated with increased JNK activation and MMP2 expression and activity, thus
      explaining in part tumor cell invasion potential. 

PMID- 25596742
TI  - Hypoxia/HIF1alpha induces lapatinib resistance in ERBB2-positive breast cancer
      cells via regulation of DUSP2.
AB  - ERBB2/HER2 belongs to the EGFR-family of receptor tyrosine kinases and its
      overexpression can promote tumor progression. Breast cancer patients with ERBB2
      amplifications are currently treated with lapatinib, a small-molecule kinase
      inhibitor that specifically blocks EGFR/ERBB2 signaling. Here, we show that
      hypoxia, via HIF-1, induces resistance to lapatinib-mediated effects in ERBB2
      expressing mammary epithelial and ERBB2-positive breast cancer cells. Lapatinib
      mediated growth inhibition and apoptosis in three-dimensional (3D) cultures are
      decreased under hypoxic conditions. Hypoxia can maintain activation of signaling
      pathways downstream from ERBB2 including AKT and ERK in the presence of
      lapatinib. HIF-1 is both required and sufficient to induce lapatinib resistance
      as overexpression of stable HIF-1 in ERBB2-expressing cells blocks lapatinib
      mediated effects and maintains ERBB2-downstream signaling under normoxic
      conditions. Under hypoxia, activation of ERK signaling is required for lapatinib
      resistance as treatment with MEK inhibitor trametinib reverses hypoxia-mediated
      lapatinib resistance. HIF-1 can bypass the lapatinib-treated inhibition of the
      ERK pathway via inhibition of the dual-specificity phosphatase 2 (DUSP2). Indeed,
      overexpression of DUSP2 in ErbB2-positve breast cancer cells reverses hypoxia
      mediated lapatinib resistance. Thus, our results provide rationale for
      therapeutic evaluation of the treatment of hypoxic ERBB2 expressing breast tumors
      with a combination of lapatinib and MEK inhibitors.

PMID- 25596743
TI  - By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer.
AB  - Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed
      in lung cancer tissues, yet, molecular mechanisms have not been examined. We
      identified that miRNA, hsa-miR-526b, is bound to the 3'-UTR of Ku80 mRNA, thus
      decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in
      NSCLC tissues compared with corresponding non-tumorous tissues, and its
      expression was inversely correlated with Ku80 upregulation. Overexpression of
      Ku80 and downregulation of hsa-miR-526b were associated with poor clinical
      outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation,
      clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b
      inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in
      NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR
      526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle
      arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo.
      In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and
      p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential
      target in cancer therapy. 

PMID- 25596744
TI  - Group I Paks as therapeutic targets in NF2-deficient meningioma.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by
      the development of multiple tumors in the central nervous system, most notably
      schwannomas and meningiomas. Mutational inactivation of NF2 is found in 40-60% of
      sporadic meningiomas, but the molecular mechanisms underlying malignant changes
      of meningioma cells remain unclear. Because group I p21-activated kinases (Paks)
      bind to and are inhibited by the NF2-encoded protein Merlin, we assessed the
      signaling and anti-tumor effects of three group-I specific Pak inhibitors -
      Frax597, 716 and 1036 - in NF2-/- meningiomas in vitro and in an orthotopic mouse
      model. We found that these Pak inhibitors suppressed the proliferation and
      motility of both benign (Ben-Men1) and malignant (KT21-MG1) meningiomas cells. In
      addition, we found a strong reduction in phosphorylation of Mek and S6, and
      decreased cyclin D1 expression in both cell lines after treatment with Pak
      inhibitors. Using intracranial xenografts of luciferase-expressing KT21-MG1
      cells, we found that treated mice showed significant tumor suppression for all
      three Pak inhibitors. Similar effects were observed in Ben-Men1 cells. Tumors
      dissected from treated animals exhibited an increase in apoptosis without notable
      change in proliferation. Collectively, these results suggest that Pak inhibitors
      might be useful agents in treating NF2-deficient meningiomas. 

PMID- 25596745
TI  - Stimulation of hERG1 channel activity promotes a calcium-dependent degradation of
      cyclin E2, but not cyclin E1, in breast cancer cells.
AB  - Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as
      marker for poor prognosis in breast cancer, and appears to play a major role in
      proliferation and therapeutic resistance in several breast cancer cells. Our
      laboratory has previously reported that stimulation of the hERG1 potassium
      channel with selective activators led to down-regulation of cyclin E2 in breast
      cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an
      ubiquitin-proteasome-dependent degradation of cyclin E2 in multiple breast cancer
      cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer
      cells. In addition we have also reveal that hERG1 stimulation induces an increase
      in intracellular calcium that is required for cyclin E2 degradation. This novel
      function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1
      were unaltered by the treatment. Our results reveal a novel mechanism by which
      hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin
      E1, and suggest a potential therapeutic use for hERG1 channel activators.

PMID- 25596747
TI  - Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon
      cancer by activating the Wnt/beta-catenin pathway.
AB  - Here we found that levels of cathelicidin, an antimicrobial peptide, were
      increased in colon cancer tissues compared to noncancerous tissues. Importantly,
      cathelicidin was mainly expressed in immune cells. Contact with tumor cells
      caused macrophages to secrete cathelicidin. Neutralization of cathelicidin, in
      vivo, significantly reduced the engraftment of macrophages into colon tumors, as
      well as proliferation of tumor cells, resulting in an inhibition of tumor growth.
      Furthermore, treatment with cathelicidin neutralizing antibody de-activated the
      Wnt/beta-catenin signaling pathway in tumor cells both in vivo and in vitro.
      Cathelicidin activated Wnt/beta-catenin signaling by inducing phosphorylation of
      PTEN, leading to activation of PI3K/Akt signaling and subsequent phosphorylation
      of GSK3beta, resulting in stabilization and nuclear translocation of beta
      catenin. These data indicate that cathelicidin, expressed by immune cells in the
      tumor microenvironment, promotes colon cancer growth through activation of the
      PTEN/PI3K/Akt and Wnt/beta-catenin signaling pathways. 

PMID- 25596746
TI  - Peritoneal expression of Matrilysin helps identify early post-operative
      recurrence of colorectal cancer.
AB  - Recurrence of colorectal cancer (CRC) following a potentially curative resection
      is a challenging clinical problem. Matrix metalloproteinase-7 (MMP-7) is over
      expressed by CRC cells and supposed to play a major role in CRC cell diffusion
      and metastasis. MMP-7 RNA expression was assessed by real-time PCR using specific
      primers in peritoneal washing fluid obtained during surgical procedure. After
      surgery, patients underwent a regular follow up for assessing recurrence.
      transcripts for MMP-7 were detected in 31/57 samples (54%). Patients were
      followed-up (range 20-48 months) for recurrence prevention. Recurrence was
      diagnosed in 6 out of 55 patients (11%) and two patients eventually died because
      of this. Notably, all the six patients who had relapsed were positive for MMP-7.
      Sensitivity and specificity of the test were 100% and 49% respectively. Data from
      patients have also been corroborated by computational approaches. Public
      available coloncarcinoma datasets have been employed to confirm MMP7 clinical
      impact on the disease. Interestingly, MMP-7 expression appeared correlated to
      Tgfb-1, and correlation of the two factors represented a poor prognostic factor.
      This study proposes positivity of MMP-7 in peritoneal cavity as a novel biomarker
      for predicting disease recurrence in patients with CRC. 

PMID- 25596749
TI  - Gab1 is essential for membrane translocation, activity and integrity of mTORCs
      after EGF stimulation in urothelial cell carcinoma.
AB  - Urothelial carcinoma is the most common type of malignancy in long-term dialysis
      patients and kidney transplant recipients in Taiwan. mTORCs (mammalian target of
      rapamycin complexes) and EGF are important in urothelial carcinoma. To identify
      the regulation of mTORCs upon EGF stimulation is necessary. mTOR integrates
      signals from growth factors via mTOR Complex 1 (mTORC1) and mTOR Complex 2
      (mTORC2). The mechanism of mTORC1 action has been widely studied; however, the
      regulation of mTORC2 has not been well studied. Here, we demonstrate that Gab1 is
      an important upstream regulator in EGF-mediated activation of mTORCs. In our
      study, we confirm that mTORCs translocate from the cytoplasm to the plasma
      membrane via the PH domain of Gab1 upon EGF stimulation. Moreover, Gab1
      associates with mTORCs. This association stabilizes the integrity of mTORCs and
      induces mTORC activity. Compared to normal bladder tissue, the expression of Gab1
      and activity of mTORCs are elevated in urothelial carcinoma. Collectively, our
      results suggest that Gab1 is an essential regulator of the EGF-mediated mTORC
      pathways and may potentially be used as a biomarker for urothelial carcinoma to
      predict diagnosis and drug response. 

PMID- 25596748
TI  - Cyclin alterations in diverse cancers: Outcome and co-amplification network.
AB  - Cyclin genes are key regulatory components of the cell cycle. With the
      development of new agents, cyclin-related genes are becoming increasingly
      important as they can be targeted. Yet, the biological implications of these
      alterations have not been fully studied. Clinical characteristics and outcome
      parameters were compared for patients harboring cyclin alterations versus not.
      CCN alterations were found in 13% of our population (50/392; all amplifications)
      and were associated with breast cancer (P < 0.0001), a higher median number of
      concomitant molecular alterations (P < 0.0001), and liver metastases (P = 0.046).
      Harboring a cyclin amplification was not associated with overall survival, the
      time to metastasis/recurrence, nor with the best progression-free survival. In a
      Cox regression model, gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001),
      and CDK alterations (P = 0.041) had a significant association with poorer overall
      survival. CCN amplifications significantly correlated with alterations in
      FGF/FGFR family genes as well as in MET and ARFRP1. An extended correlation study
      shed light on a network of co-amplifications influenced in part by genes that
      were localized on the same amplicons. CCN amplifications are common across
      cancers and had distinctive biological associations. Customized combinations
      targeting the cyclin pathway as well as the extended co- amplification network
      may be necessary in order to address resistance mechanisms. 

PMID- 25596750
TI  - Local uterine Ang-(1-7) infusion augments the expression of cannabinoid receptors
      and differentially alters endocannabinoid metabolizing enzymes in the
      decidualized uterus of pseudopregnant rats.
AB  - BACKGROUND: Endocannabinoids (ECs) are important contributors to implantation and
      decidualization and are suppressed in early pregnancy. Elevated levels of
      anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R),
      interfere with receptivity of the blastocyst. Ang-(1-7) is down-regulated in the
      implantation site (IS) in normal pregnancy at day 7 of gestation. We determined
      the effects of intra-uterine angiotensin-(1-7) [Ang-(1-7)] (24 microg/kg/h) or
      vehicle given into the left uterine horn on the ECs in the decidualized uterus.
      METHODS: Ovariectomized rats were sensitized for the decidual cell reaction by
      steroid treatment and decidualization was induced by a bolus of oil injected into
      the left horn; the right horn served as a control. RESULTS: Decidualization
      increased endometrial permeability (3.1+/-0.2 vs. 7.1+/-0.5 uterus/muscle of cpm
      of (125)I-BSA, p < 0.0001). VEGF mRNA was increased by the decidualization (1.4
      fold, p < 0.05) and by Ang-(1-7) (2.0-fold, p < 0.001). CB1R mRNA was reduced by
      decidualization (2.7-fold, p < 0.001), but increased by Ang-(1-7) (1.9-fold, p <
      0.05). CB2R mRNA was increased by decidualization (4-fold, p < 0.05) and by Ang
      (1-7) (2.4-fold, p < 0.001). The enzyme metabolizing AEA, fatty acid amide
      hydrolase (FAAH), was reduced by decidualization (7.8 fold, p < 0.001) and
      unchanged by Ang-(1-7) (p > 0.05), whereas the enzyme metabolizing 2
      arachidonoylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by
      decidualization (p > 0.05) and increased by Ang-(1-7) (1.7 fold, p < 0.001).
      CONCLUSIONS: These findings report for the first time that Ang-(1-7) augments the
      expression of CB1R, CB2R and MAGL in the decidualized uterus and thus may
      interfere with the early events of decidualization.

PMID- 25596752
TI  - Exploring the social, emotional and behavioural development of preschool
      children: is Glasgow different?
AB  - BACKGROUND: Glasgow City has poorer adolescent and adult health outcomes in
      comparison to demographically similar cities in England and the rest of Scotland.
      Until now, little exploration of differences in child development between Glasgow
      and other areas has been made. The authors hypothesized that the poorer health
      outcomes and lifestyle behaviours of adults, coupled with relative economic
      deprivation, may impact on child social, emotional and behavioural development,
      compared with children from other parts of Scotland. METHODS: Data from the
      Growing Up in Scotland national birth cohort study were used. Differences between
      Strengths and Difficulties Questionnaire (SDQ) scores and child and family
      characteristics of children living in the Greater Glasgow and Clyde (GGC) Health
      board vs. other health boards were examined. Logistic regression and linear
      regression models were fitted in order to explore independent associations
      between health board and SDQ raw and banded scores, respectively, whilst
      controlling for other contributing factors. RESULTS: Children in GGC were
      demographically different from those in other areas of Scotland, being
      significantly more likely to live in the most deprived areas, yet no difference
      was found in relation to the mental health of preschool-aged children in GGC.
      Children in GGC had slightly better SDQ Conduct Problems scores once demographic
      factors were controlled for. CONCLUSIONS: At 46 months, there does not appear to
      be any difference in Glasgow with regards to social, emotional and behavioural
      development. Glaswegian children appear to have slightly fewer conduct problems
      at this age, once demographics are taken into account. A range of theories are
      put forward as to why no differences were found, including the inclusion of areas
      adjacent to Glasgow City in the analysis, sleeper effects, and rater bias.

PMID- 25596753
TI  - Up-regulation of miR-9 target CBX7 to regulate invasion ability of bladder
      transitional cell carcinoma.
AB  - BACKGROUND: Bladder urothelial carcinoma is the most common genitourinary system
      cancer in China. The objective of this study was to investigate whether the miR-9
      can regulate the invasion ability of human bladder transitional cell carcinoma
      cells by down-regulation of CBX7. MATERIAL/METHODS: The expression of miR-9 was
      detected by quantitative real-time PCR in bladder transitional cell carcinomas
      (TCC) and normal bladder transitional cell (NBTC) samples. Bioinformatics
      software was used to predict some potential target genes of miR-9. T24 cells were
      transfected with pre-miR-9, and the CBX7 protein expression was detected by
      Western blot. Luciferase activities assay was selected to verify that CBX7 was a
      direct and specific gene of miR-9. T24 cells were transfected with pcDNA-CBX7,
      and the expression of CBX7 gene was detected. Then, the transwell assay was used
      to detect the invasion ability of T24 cells with CBX7 over-expression. RESULTS:
      The expression of miR-9 increased significantly in human TCC specimens compared
      to that in NBTC specimens. TargetScan and PicTar software programs predicted CBX7
      gene was a target gene of miR-9. The pre-miR-9 could up-regulate the miR-9
      expression and down-regulate CBX7 protein expression. The luciferase activities
      assay verified that CBX7 gene was a direct and specific target gene of miR-9. The
      pcDNA-CBX7 transfection could up-regulate the CBX7 protein expression, and the
      invasion ability of T24 cells with CBX7 over-expression decreased significantly.
      CONCLUSIONS: Aberrantly expressed miR-9 contributes to T24 cells invasion, partly
      through directly down-regulating CBX7 protein expression in TCC. This miRNA
      signature offers a new potential therapeutic target for TCC.

PMID- 25596754
TI  - Severe maternal outcomes and their predictors among Pakistani women in the WHO
      Multicountry Survey on Maternal and Newborn Health.
AB  - OBJECTIVE: To determine the incidence of, and the demographic and obstetric
      factors associated with, severe maternal outcome (SMO) among women presenting at
      healthcare facilities in Pakistan. METHODS: A cross-sectional study was conducted
      in 16 healthcare facilities across Pakistan that had been selected for the WHO
      Multicountry Survey on Maternal and Newborn health. The hospital records of women
      who delivered at a participating facility or were admitted with SMO (defined as
      maternal death or near miss) within 7 days of delivery/abortion were reviewed for
      a period of 2-3 months in 2011. The incidence of SMO, its associated demographic
      and obstetric characteristics, and the influence of various maternal health
      interventions were assessed. RESULTS: Among 13 175 included women, 132 (1.0%) had
      an SMO (94 [0.7%] near miss and 38 [0.3%] died). The maternal mortality ratio was
      299 deaths per 100 000 live births. Major causes of SMO included postpartum
      hemorrhage (64 [48.5%] women), hypertensive disorders (34 [25.8%]), and ruptured
      uterus (9 [6.8]). Illiteracy, anemia, and several obstetric complications (e.g.
      eclampsia) were significant contributors. CONCLUSION: Improving education,
      nutrition, and uniform implementation of obstetric care protocols are needed for
      better maternal and neonatal health in Pakistan.

PMID- 25596755
TI  - Experiences and beliefs of Malawian women who have delivered with a traditional
      birth attendant.
AB  - OBJECTIVE: To explore the beliefs and experiences of Malawian women who have
      delivered with a traditional birth attendant (TBA). METHODS: In a qualitative
      study, 20 face-to-face in-depth interviews and three focus group discussions were
      conducted between February and May 2013. Women aged 18 years or older and who had
      a history of delivery with a TBA were recruited from three health centers in
      Lilongwe District. Their responses were independently coded, and content analysis
      was used to develop themes and subthemes. RESULTS: A total of 46 women
      participated. Most participants cited difficulties relating to transport and/or
      unsupportive or unavailable husbands as factors that prohibited their delivery at
      a health facility. Most had not had a specific delivery plan. The participant
      responses indicated a discordance between knowledge and practices for safe
      delivery. CONCLUSION: Strategies to decrease deliveries with TBAs should focus on
      helping women to develop delivery plans to cope with the potential social or
      situational obstacles of getting to a facility. Women desire health facilities
      that provide quality care, emotional support, and personalized care during labor
      and delivery.

PMID- 25596756
TI  - The laparoscopic approach to distal pancreatectomy for ductal adenocarcinoma
      results in shorter lengths of stay without compromising oncologic outcomes.
AB  - BACKGROUND: The oncologic equivalence of laparoscopic distal pancreatectomy (LDP)
      to open pancreatectomy (ODP) for ductal adenocarcinoma (DAC) is not established.
      METHODS: The National Cancer Data Base was used to compare perioperative outcomes
      following LDP and ODP for DAC between 2010 and 2011. RESULTS: One hundred forty
      five patients underwent LDP; 625 underwent ODP. Compared with ODP, patients
      undergoing LDP were older (68 +/- 10.1 vs 66 +/- 10.5 years, P = .027), more
      likely treated in academic centers (70% vs 59%, P = .01), and had shorter
      hospital stays (6.8 +/- 4.6 vs 8.9 +/- 7.5 days, P < .001). Demographic data,
      lymph node count, 30-day unplanned readmission, and 30-day mortality were
      identical between groups. Multivariable regression identified a lower probability
      of prolonged length of stay with LDP (odds ratio .51, 95% confidence interval
      .327 to .785, P = .0023). There was no association between surgical approach and
      node count, readmission, or mortality. CONCLUSION: LDP for DAC provides shorter
      postoperative lengths of stay and rates of readmission and 30-day mortality
      similar to OPD without compromising perioperative oncologic outcomes.

PMID- 25596757
TI  - Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a
      pyrrolo[2,3-d]pyrimidine scaffold.
AB  - A series of novel reversible BTK inhibitors was designed based on the structure
      of the recently reported preclinical drug RN486. Knowledge of the binding mode of
      RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine
      to conformationally restrain key pharmacophoric groups within the molecule.
      Comprehensive SAR was disclosed and the most promising compound 4x displayed
      superior activity both in BTK enzyme (IC50=4.8nM) and cellular inhibition
      (IC50=17nM) assays to that of RN486. 

PMID- 25596758
TI  - Synthesis, biological evaluation and docking analysis of a new series of
      methylsulfonyl and sulfamoyl acetamides and ethyl acetates as potent COX-2
      inhibitors.
AB  - We report herein the synthesis, biological evaluation and docking analysis of a
      new series of methylsulfonyl, sulfamoyl acetamides and ethyl acetates that
      selectively inhibit cyclooxygenase-2 (COX-2) isoform. Among the newly synthesized
      compounds, some of them were endowed with a good activity against COX-2 and a
      good selectivity COX-2/COX-1 in vitro as well as a desirable analgesic activity
      in vivo, proving that replacement of the ester moiety with an amide group gave
      access to more stable derivatives, characterized by a good COX-inhibition. 

PMID- 25596759
TI  - Application of ion exchange and extraction chromatography to the separation of
      actinium from proton-irradiated thorium metal for analytical purposes.
AB  - Actinium-225 (t1/2=9.92d) is an alpha-emitting radionuclide with nuclear
      properties well-suited for use in targeted alpha therapy (TAT), a powerful
      treatment method for malignant tumors. Actinium-225 can also be utilized as a
      generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for
      TAT. Actinium-225 can be produced via proton irradiation of thorium metal;
      however, long-lived (227)Ac (t1/2=21.8a, 99% beta(-), 1% alpha) is co-produced
      during this process and will impact the quality of the final product. Thus,
      accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is
      dependent on beam energy, irradiation time and target design. Accurate actinium
      assays, in turn, require efficient separation of actinium isotopes from both the
      Th matrix and highly radioactive activation by-products, especially
      radiolanthanides formed from proton-induced fission. In this study, we introduce
      a novel, selective chromatographic technique for the recovery and purification of
      actinium isotopes from irradiated Th matrices. A two-step sequence of cation
      exchange and extraction chromatography was implemented. Radiolanthanides were
      quantitatively removed from Ac, and no non-Ac radionuclidic impurities were
      detected in the final Ac fraction. An (225)Ac spike added prior to separation was
      recovered at >= 98%, and Ac decontamination from Th was found to be >= 10(6). The
      purified actinium fraction allowed for highly accurate (227)Ac determination at
      analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 MUCi).

PMID- 25596760
TI  - Computer-assisted multi-segment gradient optimization in ion chromatography.
AB  - This study reports simulation and optimization of ion chromatography separations
      using multi-segment gradient elution. First, an analytical expression for the
      gradient retention factor under these complex elution profiles was derived. This
      allows a rapid retention time prediction calculations under different gradient
      conditions, during computer-assisted method development. Next, these analytical
      expressions were implemented in an in-house written Matlab((r)) routine that
      searches for the optimal (multi-segment) gradient conditions, either via a four
      segment grid search or via the recently proposed one-segment-per-component
      search, in which the slope is adjusted after the elution of each individual
      component. Evaluation of the retention time simulation and optimization
      approaches was performed on a mixture of 18 inorganic anions and different
      subsets with varying number of compounds. The two considered multi-segment
      gradient optimization searches resulted in similar proposed gradient profiles,
      and corresponding chromatograms. Moreover, the resultant chromatograms were
      clearly superior to the chromatograms obtained from the best simple linear
      gradient profiles, found via a fine grid search. The proposed approach is useful
      for automated method development in ion chromatography in which complex elution
      profiles are often used to increase the separation power. 

PMID- 25596761
TI  - Theoretical and experimental studies on sequential two-diffusional sample
      injection for capillary electrophoresis.
AB  - We report here theoretical and experimental studies on the sequential diffusion
      injection (SDI) for CE analysis. Based on the Fick's second law, a theoretical
      model for two-dimensional (2-D) diffusion has been developed for our SDI system.
      The 2-D diffusion model has been demonstrated via systematic experimental studies
      using standard nicotinamide adenine dinucleotide (NADH) as the model analyte. The
      results show that the dependence of the NADH peak area (corresponding to the
      injection amount) on the initial sample concentration, the injection time or the
      capillary-gap distance is consistent with the deduction of the 2-D diffusion
      model. It is indicated that the 2-D diffusion, both in longitudinal and
      transverse directions of the capillary, enhances the injection efficiency in
      comparison to classical concentration diffusion on the plane interface, and
      improves the accuracy of the sequential injection without any physical
      disturbance of the capillary inlet. With the insight understanding of the
      injection mechanism, we have successfully applied the SDI method for sequential
      CE analysis of amino acids mixture and online assay of the glucose-6-phosphate
      dehydrogenase-catalyzed reaction. The present study showed that the SDI is a
      versatile tool for efficient and accurate sequential CE analysis, not only for
      online monitoring various bioprocesses but also for continuous analyzing complex
      samples based on capillary electrophoresis. 

PMID- 25596762
TI  - Methacrylate monolith chromatography as a tool for waterborne virus removal.
AB  - Enteric viruses are commonly present in environmental waters and represent the
      major cause of waterborne infections and outbreaks. Since traditional wastewater
      treatments fail to remove enteric viruses in the water purification process, they
      are released daily into environmental waters. Monolithic supports have enabled
      chromatography to enter the field of virology. They have been successfully used
      in virus purification and concentration. In this work quaternary amine (QA)
      methacrylate monoliths were exploited to remove enteric viruses from wastewater
      treatment plant effluent. Expectedly, chromatographic processing of such a
      complex medium was troublesome, even for monoliths, characterized by extremely
      large pore dimensions. This problem was solved by introducing a pre-step
      chromatography using hydroxyl (OH) methacrylate monoliths. This way, molecules,
      that would hinder virus binding to the anion-exchanger monolith, were removed. As
      a result, the OH pre-column reduced backpressure increase on the subsequent anion
      exchanger column, and increased both QA column binding capacity and life time.
      Wastewater effluent samples were successfully purified from five waterborne
      enteric viruses (rotavirus, norovirus genogroup I and II, astrovirus, sapovirus),
      below the detection limit of RT-qPCR. The breakthrough of the rotavirus binding
      capacity was not reached for concentrations that significantly exceeded those
      expected in effluent waters. The obtained results confirm that methacrylate
      monoliths can be a valuable tool for simultaneous removal of different waterborne
      viruses from contaminated water sources. 

PMID- 25596763
TI  - Comparison of conventional liquid chromatography-tandem mass spectrometry versus
      microflow liquid chromatography-tandem mass spectrometry within the framework of
      full method validation for simultaneous quantification of 40 antidepressants and
      neuroleptics in whole blood.
AB  - Microflow liquid chromatography (MFLC) coupled to mass spectrometry (MS) is
      claimed to improve analysis throughput, reduce matrix effects and lower mobile
      phase consumption. This statement was checked within the framework of method
      validation of a multi-analyte procedure in clinical and forensic toxicology
      employing MFLC-MS/MS and conventional LC-MS/MS. 200 MUL whole blood were spiked
      with 50 MUL internal standard mixture and extracted by protein precipitation. The
      concentrated extract was separated into two vials. One was analyzed using a
      Thermo Fisher Ultimate liquid chromatography system coupled to an ABSciex 5500
      QTrap mass spectrometer (LC-MS/MS) and one by an ABSciex Eksigent Microflow LC
      system coupled to an ABSciex 4500 linear ion trap quadrupole MS (MFLC-MS/MS).
      Both methods were fully validated and compared in terms of selectivity,
      stability, limits, calibration model, recovery (RE), matrix effects (ME), bias,
      imprecision and beta tolerance interval for 40 antidepressants and neuroleptics
      including 9 metabolites. Both methods had comparable LODs, LOQs and calibration
      models with some exceptions. The MFLC system showed slightly higher coefficients
      of variation (CVs) in the RE experiments. ME were reproducible in both systems
      but with lower CVs in the conventional LC system. Acceptance criteria for
      imprecision and bias were fulfilled for 32 analytes on the LC and for 28 analytes
      on the MFLC system. Beta tolerance intervals indicated better reproducibility in
      terms of narrower intervals for the conventional LC system. The advantages of the
      MFLC system were low mobile phase consumption, short run time, and better peak
      separation. The systems were comparable in terms of peak interference, LOD, ME,
      bias and imprecision. The advantages of the conventional LC system were more data
      points per peak, linear calibration models, stable retention times and better
      beta tolerance intervals. Due to higher robustness, the conventional LC system
      was finally chosen for routine application in forensic toxicology.

PMID- 25596764
TI  - Modeling Langmuir isotherms with the Gillespie stochastic algorithm.
AB  - The overall goal of this work is to develop a robust modeling approach that is
      capable of simulating single and multicomponent isotherms for biological
      molecules interacting with a variety of adsorbents. Provided the ratio between
      the forward and reverse adsorption/desorption constants is known, the Gillespie
      stochastic algorithm has been shown to be effective in modeling isotherms
      consistent with the Langmuir theory and uptake curves that fall outside this
      traditional approach. We have used this method to model protein adsorption on ion
      exchange adsorbents, hydrophobic interactive adsorbents and ice crystals. In our
      latest efforts we have applied the Gillespie approach to simulate binary and
      ternary isotherms from the literature involving gas-solid adsorption
      applications. In each case the model is consistent with the experimental results
      presented.

PMID- 25596766
TI  - [Mutation in the SLC17A9 gene in familial superficial actinic disseminated
      porokeratosis].

PMID- 25596765
TI  - Robust whole-brain segmentation: application to traumatic brain injury.
AB  - We propose a framework for the robust and fully-automatic segmentation of
      magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with
      Expectation-Maximisation based refinement" (MALP-EM). The presented approach is
      based on a robust registration approach (MAPER), highly performant label fusion
      (joint label fusion) and intensity-based label refinement using EM. We further
      adapt this framework to be applicable for the segmentation of brain images with
      gross changes in anatomy. We propose to account for consistent registration
      errors by relaxing anatomical priors obtained by multi-atlas propagation and a
      weighting scheme to locally combine anatomical atlas priors and intensity-refined
      posterior probabilities. The method is evaluated on a benchmark dataset used in a
      recent MICCAI segmentation challenge. In this context we show that MALP-EM is
      competitive for the segmentation of MR brain scans of healthy adults when
      compared to state-of-the-art automatic labelling techniques. To demonstrate the
      versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain
      images into 134 regions from subjects who had sustained traumatic brain injury
      (TBI). We employ a protocol to assess segmentation quality if no manual reference
      labels are available. Based on this protocol, three independent, blinded raters
      confirmed on 13 MR brain scans with pathology that MALP-EM is superior to
      established label fusion techniques. We visually confirm the robustness of our
      segmentation approach on the full cohort and investigate the potential of derived
      symmetry-based imaging biomarkers that correlate with and predict clinically
      relevant variables in TBI such as the Marshall Classification (MC) or Glasgow
      Outcome Score (GOS). Specifically, we show that we are able to stratify TBI
      patients with favourable outcomes from non-favourable outcomes with 64.7%
      accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR
      images. Furthermore, we are able to differentiate subjects with the presence of a
      mass lesion or midline shift from those with diffuse brain injury with 76.0%
      accuracy. The thalamus, putamen, pallidum and hippocampus are particularly
      affected. Their involvement predicts TBI disease progression. 

PMID- 25596767
TI  - Analytical accuracy and precision of two novel Point-of-Care systems for INR
      determination.
AB  - BACKGROUND: Portable point-of-care (POC) instruments for determination of the
      whole blood prothrombin time (PT) have been available for the last three decades.
      Recently, two novel POC instruments for PT and International Normalized Ratio
      (INR) determination in whole blood have been manufactured. The purpose of this
      study was to compare INR values obtained with the novel instruments (microINR(r)
      and ProTime InRhythmTM) to the INR determined with the international standard for
      thromboplastin rTF/09. MATERIALS AND METHODS: In 60 patients treated with vitamin
      K-antagonists, venous whole blood was analysed with four different types of POC
      instruments including the novel ones. In the same patients, citrated plasma was
      analysed with the international standard rTF/09 and the manual tilt tube
      technique for clotting time determination. We assessed the bias of the INR read
      from the POC instruments relative to the international standard. To study the
      imprecision of the two novel POC instruments, duplicate INR determinations were
      performed. RESULTS: The results obtained with the two novel POC instruments were
      positively correlated with those of the international standard rTF/09. However,
      there was a significant bias between INR read from the novel instruments and the
      INR determined with rTF/09 (P < 0.001). The mean bias was -13.7% (MicroINR) and 
      9.3% (InRhythm). The imprecision coefficient of variation in venous blood was
      5.0% and 5.1%, respectively. CONCLUSION: The imprecision of the two novel
      instruments is acceptable with respect to the average within-subject variation of
      the INR. The accuracy of the systems is borderline and should be improved by the
      manufacturers.

PMID- 25596768
TI  - Inflammatory bowel disease increases the risks of deep vein thrombosis and
      pulmonary embolism in the hospitalized patients: a nationwide cohort study.
AB  - BACKGROUND & AIMS: We conducted a nationwide, population-based cohort study to
      evaluate the effects of inflammatory bowel disease (IBD) on the risks of
      developing deep vein thrombosis (DVT) and pulmonary embolism (PE) in Taiwan.
      METHODS: We randomly selected the study cohort with IBD from the National Health
      Insurance (NHI) database (N = 23.74 million) and the control cohort without IBD
      who was frequency-matched the study cohort based on age, sex, and index year to
      each IBD patient between 2000 and 2010. Using a follow-up period ending in 2011,
      we analyzed the risks of DVT and PE using Cox proportional hazard regression
      analyses. RESULTS: The 11 445 IBD patients and 45 780 controls were followed 65
      256 and 293 377 person-years, respectively. After adjusting for age, sex, and
      comorbidities, the risks of IBD patients developing DVT and PE was 1.98-fold and
      1.80-fold higher, respectively, than those of the comparison cohort. The IBD
      patients presenting with 2 or more annual hospitalizations exhibited a
      significantly greater risk of developing DVT (adjusted hazard ratio [HR] 32.9,
      95% confidence interval [CI] 20.5-52.8) and PE (adjusted HR = 24.2, 95% CI = 11.1
      52.9) than did the comparison cohort. Women with IBD showed a significantly
      greater risk of DVT and PE than did the comparison cohort (adjusted HR = 1.80,
      95% CI = 1.18-2.78 for DVT and adjusted HR=2.08, 95% CI = 1.14-3.80 for PE
      respectively). CONCLUSION: The risks of DVT and PE are significantly higher in
      IBD patients compared with risks in the general population. WHAT IS CURRENT
      KNOWLEDGE: Thromboembolic complications are easily overlooked in IBD patients.
      WHAT IS NEW HERE: The risks of DVT and PE are significantly higher in IBD
      patients.

PMID- 25596769
TI  - More efficient reversal of dabigatran inhibition of coagulation by activated
      prothrombin complex concentrate or recombinant factor VIIa than by four-factor
      prothrombin complex concentrate.
AB  - The number of patients on antithrombotic treatment due to atrial fibrillation and
      venous thromboembolism is increasing fast due to an aging population. A growing
      proportion will be treated with novel oral anticoagulants, the first in clinical
      use was the direct oral thrombin inhibitor dabigatran (Pradaxa(r)). A small
      percentage of the patients on dabigatran will experience serious bleeding or be
      in need of urgent surgery. The aim of this study was to test the effects of
      different hemostatic agents in potentially reversing the anticoagulant effects in
      vitro in blood or platelet-rich plasma (PRP) spiked with dabigatran. Whole blood
      or PRP was spiked with the active substance dabigatran, 200 MUg/L. We measured
      clotting time being induced by 1.4 pmol/L tissue factor using the instrument
      ReoRox2TM and initial clot growth velocity from a tissue factor covered surface
      using the instrument Thrombodynamics Analyzer T-2TM. Dabigatran prolonged
      clotting time 5-fold but reduced clot growth velocity only slightly. The
      reversing effects of prothrombin complex concentrates (PCC), activated PCC (APCC)
      and recombinant activated factor VII (rFVIIa) were then tested. APCC (1.8 U/mL)
      reduced the prolonged clotting time by 1/3, rFVIIa (2 MUg/L) only slightly (n =
      10-20). The reduction was not significant using Mann-Whitney test but significant
      using t-test with Bonferronis' correction for multiple comparisons, whereas PCC
      (0.56 U/mL) had no effect on clotting time. APCC doubled initial clot growth
      velocity, although even more in the absence of dabigatran. In conclusion, APCC
      and rFVIIa, but not PCC, seem to reverse, at least partially, some effects of
      dabigatran on coagulation parameters. Systematic evaluation of case reports,
      registries and, ultimately, randomized clinical trials are needed to elucidate
      potential benefit for patients.

PMID- 25596770
TI  - Risk factors for inguinal hernia in middle-aged and elderly men: results from the
      Rotterdam Study.
AB  - BACKGROUND: Prospective data on risk factors and the incidence of inguinal hernia
      are sparse, especially in an elderly population. The aim of this study was to
      determine the incidence of and risk factors for inguinal hernia. METHODS: We
      analyzed data from the Rotterdam Study, a prospective cohort study that observed
      the general population aged >=45 years of Ommoord, a district in Rotterdam, from
      baseline (1990) over a period of >20 years. Diagnoses of inguinal hernia were
      obtained from hospital discharge records and records from general practitioners.
      Multivariate regression analysis was performed to determine risk factors for
      inguinal hernia development. RESULTS: Among 5,780 men, with a total of 50,802
      person-years, who did not have a hernia at baseline, 416 cases of inguinal hernia
      (7.2%) occurred. The 20-year cumulative incidence was 14%. Age-adjusted hazard
      ratio (HR) for inguinal hernia for men relative to women was 12.4 (95% CI, 9.5
      16.3; P < .001). On multivariate analysis, the risk of inguinal hernia increased
      with advancing age (HR per 1-year increase in age, 1.03; 95% CI, 1.02-1.04; P <
      .001). Participants with a body mass index (BMI) of 25-30 kg/m2 had an HR of 0.72
      (95% CI, 0.58-0.89; P = .003) compared with a BMI of <25; a BMI of >30 had an
      associated HR of 0.63 (95% CI, 0.42-0.94; P = .025). CONCLUSION: Inguinal hernia
      is common in the middle-aged and elderly male population and its incidence
      increases with advancing age. Overweight or obese patients have a lesser risk of
      developing an inguinal hernia.

PMID- 25596772
TI  - Electrical stimulation for gastroesophageal reflux disease: formal randomized
      clinical trials are needed.

PMID- 25596773
TI  - Noninvasive intraductal papillary mucinous neoplasms and mucinous cystic
      neoplasms: recurrence rates and postoperative imaging follow-up.
AB  - BACKGROUND: Although surveillance guidelines for resected invasive mucinous
      neoplastic cysts are well-established, those for noninvasive cysts are not
      defined. We used our experience with resected noninvasive mucinous neoplastic
      cysts to define recurrence rates and the optimal frequency of postoperative
      imaging follow-up. METHODS: We reviewed the medical records of 134 patients with
      resected, pathologically confirmed noninvasive mucinous neoplasms between 2002
      and 2012. Demographics, comorbidities, cyst characteristics, and recurrence were
      evaluated. Survival analysis was used to estimate the distribution of time to
      recurrence and regression models were used to investigate factors associated with
      recurrence. RESULTS: Eighty-seven patients with intraductal papillary mucinous
      neoplasms (IPMNs) were compared with 47 patients with mucinous cystic neoplasms
      (MCNs). Those with MCNs were more often females (P = .001), significantly younger
      (P = .001), more symptomatic (P = .009), and had cysts more often located in the
      tail (P < .001). Median follow-up was 42 months. Recurrence rates for IPMNs were
      0%, 5%, and 10% versus 0% for MCNs respectively at postoperative years 1, 2, and
      3 (P = .014). On multivariable analysis, size >3 cm (P = .027), higher grade
      dysplasia (P = .043), and positive resection margins (P < .001) were
      significantly associated with recurrence. CONCLUSION: Resected noninvasive IPMNs
      with moderate- or high-grade dysplasia and negative resection margins require
      imaging follow-up every 2 years, given the 16% overall recurrence rate. Although
      the follow-up interval for noninvasive, low-grade, dysplastic IPMNs with negative
      margins could be lengthened, all noninvasive IPMNs having positive margins
      require yearly follow-up at the minimum. Resected noninvasive MCNs--irrespective
      of grade and margin status--do not require surveillance, although the development
      of branch duct-IPMNs in the remnant pancreas can be investigated in the long term
      at the discretion of the provider.

PMID- 25596775
TI  - [Ankyloblepharon filiforme adnatum].

PMID- 25596774
TI  - Surgical management of dysthyroid diplopia with preservation of the anterior
      ciliary vascularization: review of ten cases.
AB  - PURPOSE: During the surgical correction of dysthyroid diplopia, the risk of
      ischemia by transection of the anterior ciliary arteries is well-known. In order
      to avoid this, we modified the classical surgical technique: (1) through the
      preservation of the vascular pedicles during muscle recession and (2) if
      necessary, through a plication (instead of a resection) of the ipsilateral
      antagonist muscle. The objective to be achieved is thus the resolution of the
      diplopia without ischemic complications. SUBJECTS AND METHODS: We report a
      prospective series of 10 patients with dysthyroid ophthalmopathy, causing
      strabismic diplopia, all operated on by the same surgeon (BR) after at least 12
      months of euthyroidism. Data collection included: history of previous
      decompressive surgery, surgical procedure, and oculomotor status before and after
      surgery. RESULTS: Ten patients (8 females), aged 51 to 74 years (mean age, 58.00
      +/- 7.62 years), were collected between 2008 and 2012. All patients had one or
      more vascular risk factors (diabetes, smoking, obesity, high blood pressure).
      With a follow-up from 16 to 67 months (mean +/- SD 27.7 months +/- 14.87),
      surgical outcomes were excellent: diplopia was cured in all cases, with recovery
      of stereoscopic vision. We had no operative or postoperative complications.
      CONCLUSIONS: The technique of preservation of the anterior ciliary
      vascularization, which is particularly justified for these fragile patients, is
      compatible with moderate muscle recessions. For larger deviations, in which a
      larger recession might increase the proptosis, it is possible to add a plication
      of the ipsilateral antagonist. This surgical technique made possible the
      suppression of the diplopia in all cases.

PMID- 25596776
TI  - A novel rotation generator of hydrodynamic cavitation for waste-activated sludge
      disintegration.
AB  - The disintegration of raw sludge is very important for enhancement of the biogas
      production in anaerobic digestion process as it provides easily degradable
      substrate for microorganisms to perform maximum sludge treatment efficiency and
      stable digestion of sludge at lower costs. In the present study the
      disintegration was studied by using a novel rotation generator of hydrodynamic
      cavitation (RGHC). At the first stage the analysis of hydrodynamics of the RGHC
      were made with tap water, where the cavitation extent and aggressiveness was
      evaluated. At the second stage RGHC was used as a tool for pretreatment of a
      waste-activated sludge (WAS), collected from wastewater treatment plant (WWTP).
      In case of WAS the disintegration rate was measured, where the soluble chemical
      oxygen demand (SCOD) and soluble Kjeldahl nitrogen were monitored and
      microbiological pictures were taken. The SCOD increased from initial 45 mg/L up
      to 602 mg/L and 12.7% more biogas has been produced by 20 passes through RGHC.
      The results were obtained on a pilot bioreactor plant, volume of 400 L.

PMID- 25596777
TI  - Suicide attempt rates and intervention effects in women of Turkish origin in
      Berlin.
AB  - PURPOSE: Ethnic minority groups show elevated suicide attempt rates across
      Europe. Evidence suggests a similar trend for women of Turkish origin in Germany,
      yet data on suicidal behaviour in minorities in Germany is scarce. The objective
      was to examine rates of suicidal behaviour, underlying motives, and to explore
      the effectiveness of an intervention program. METHODS: From 05/2009-09/2011, data
      on all suicide attempts among women of Turkish origin who presented at a hospital
      based emergency unit in Berlin, Germany, were collected. A multi-modal
      intervention was conducted in 2010 and the effects of age, generation and the
      intervention on suicide attempt rates were examined. RESULTS: At the start, the
      highest rate was found in women aged 18-24years with 225.4 (95% CI=208.8
      242.0)/100,000. Adjustment disorder was the most prevalent diagnosis with 49.7%
      (n=79), being more common in second-generation women (P=.004). Further analyses
      suggested an effect of the intervention in the youngest age group (trend change
      of beta=-1.25; P=.017). CONCLUSION: Our findings suggest a particularly high rate
      of suicide attempts by 18-24-year-old, second-generation women of Turkish origin
      in Berlin. Furthermore, our results suggest a trend change in suicide attempts in
      women aged 18-24years related to a population-based intervention program.

PMID- 25596778
TI  - Is virus coinfection a predictor of severity in children with viral respiratory
      infections?
AB  - Molecular assays have resulted in increased detection of viral respiratory
      infections, including virus coinfection, from children with acute respiratory
      infections. Yet the clinical severity of virus coinfection compared to single
      virus infection remains uncertain. We performed a retrospective study of children
      presenting with acute respiratory infections comparing clinical severity of
      single respiratory virus infection to virus coinfection, detected on midturbinate
      swabs by molecular assays. Patient characteristics and measures of clinical
      severity were abstracted from health records. A total of 472 virus-infected
      children were included, 391 with a single virus infection and 81 with virus
      coinfection. Virus status did not affect admission to hospital (odds ratio (OR) =
      0.8; 95 % confidence interval (CI) 0.5-1.4; p 0.491) or clinical disease severity
      among inpatients (OR = 0.8; 95% CI 0.5-1.5; p 0.515) after adjusting for age and
      underlying comorbidities. However, children infected with rhinovirus/enterovirus
      (HRV/ENT) alone were more likely to be admitted to the hospital compared to those
      coinfected with HRV/ENT and at least another virus, although this was not
      significant in multivariable analyses (OR 0.47; 95% CI 0.22-1.0; p 0.051). In
      multivariable analyses, children coinfected with respiratory syncytial virus
      (RSV) and other viruses were significantly more likely to present with
      radiologically confirmed pneumonia compared to those with an isolated RSV
      infection (OR 3.16, 95% CI 1.07-9.34, p 0.037). Equivalent clinical severity was
      observed between children with single virus infection and virus coinfection,
      although children coinfected with RSV and other viruses presented more frequently
      with pneumonia than those with single RSV infection. Increased disease severity
      observed among children with single HRV/ENT infection requires further
      investigation.

PMID- 25596779
TI  - Staphylococcus aureus complex from animals and humans in three remote African
      regions.
AB  - Staphylococcus schweitzeri has been recently considered to be a highly divergent
      Staphylococcus aureus clade and usually colonises nonhuman primates and bats in
      sub-Saharan Africa. Its transmissibility to humans remains unclear. We therefore
      investigated the transmission of S. aureus and S. schweitzeri among humans,
      domestic animals, and wildlife in three remote African regions. A cross-sectional
      study on nasal and pharyngeal colonisation in humans (n = 1288) and animals (n =
      698) was performed in Cote d'Ivoire, Gabon, and Democratic Republic of Congo (DR
      Congo). Isolates were subjected to spa typing and multilocus sequence typing.
      Antimicrobial susceptibility and selected virulence factors were tested. S.
      schweitzeri was found in monkeys from all study sites but no transmission to
      humans was evident, despite frequent contact of humans with wildlife. In
      contrast, human-associated S. aureus sequence types (ST1, ST6, ST15) were
      detected in domestic animals and nonhuman primates, pointing toward a human-to
      monkey transmission in the wild. The proportion of methicillin-resistant S.
      aureus (MRSA) among all S. aureus was 0% (Gabon), 1.7% (DR Congo), and 5.3% (Cote
      d'Ivoire). The majority of MRSA isolates belonged to the African clone ST88. In
      conclusion, we did not find any evidence for a transmission of S. schweitzeri
      from animals to humans. However, such a transmission might remain possible due to
      the close phylogenetic relation of humans and nonhuman primates. The ST88-MRSA
      clone was widespread in Cote d'Ivoire but not in Gabon and DR Congo.

PMID- 25596780
TI  - Polyclonality among clinical strains of non-pigmented rapidly growing
      mycobacteria: phenotypic and genotypic differences and their potential
      implications.
AB  - To investigate the potential implications (especially the implications in
      clinical significance and antimicrobial susceptibility) of polyclonality among
      rapidly growing mycobacteria, we performed random amplified polymorphic DNA
      analysis in 64 clinical isolates of which the clinical significance was
      established. Phenotypic characteristics (antimicrobial susceptibility test,
      colony morphology and growth rate) of each clone were studied. Polyclonality was
      detected in 13 of the isolates (20.3%). There was a relationship between
      monoclonality and clinical significance (p 0.0096). Monoclonal and polyclonal
      isolates showed different behaviour in antimicrobial susceptibility. There was a
      strong relationship between monoclonality and those species that are more
      pathogenic for humans, and also with clinical significance of the isolates. 

PMID- 25596782
TI  - Whole genome sequencing of clinical isolates of Giardia lamblia.
AB  - Clinical isolates from protozoan parasites such as Giardia lamblia are at present
      practically impossible to culture. By using simple cyst purification methods, we
      show that Giardia whole genome sequencing of clinical stool samples is possible.
      Immunomagnetic separation after sucrose gradient flotation gave superior results
      compared to sucrose gradient flotation alone. The method enables detailed
      analysis of a wide range of genes of interest for genotyping, virulence and drug
      resistance. 

PMID- 25596781
TI  - Concurrent interspecies and clonal dissemination of OXA-48 carbapenemase.
AB  - Several isolates of four different carbapenemase-producing Enterobacteriaceae
      species were recovered from a patient hospitalized for 4 months in a teaching
      hospital in Madrid. These species comprised seven Klebsiella pneumoniae belonging
      to ST15, four Escherichia coli belonging to ST2531, two Serratia marcescens and
      one Citrobacter freundii. This patient was the index case of a small outbreak of
      four patients infected and/or colonized by carbapenemase-producing K. pneumoniae.
      Molecular results identified the bla(OXA-48) gene in all Enterobacteriaceae
      isolates from the index case and in all isolates from the other three patients,
      suggesting intra- and interpatient dissemination. Our results highlight the great
      ability of OXA-48 carbapenemase to spread among different enterobacterial species
      by both clonal and nonclonal dissemination.

PMID- 25596783
TI  - Amniocentesis for the detection of congenital toxoplasmosis: results from the
      nationwide Austrian prenatal screening program.
AB  - Prenatal diagnosis of congenital toxoplasmosis (CT) influences therapeutical
      management in pregnant women and their offspring. In Austria, a nationwide
      serological healthcare program to identify potential maternal toxoplasma
      infections during pregnancy exists. We assessed the clinical use of amniocentesis
      for toxoplasma-specific polymerase chain reaction (PCR) on amniotic fluid to
      detect CT. Data on serology, amniocentesis, PCR, complications, treatment, and
      paediatric clinical outcome were collected retrospectively among the birth cohort
      1992-2008. There were 1386 women with amniocentesis, but only in 707 cases (51%)
      was acute maternal infection confirmed serologically. A high proportion (49%) of
      amniocenteses with negative PCR results in women with chronic infection or
      seronegativity were performed without clinical justification for the women or
      their foetuses. The positive and negative predictive values of PCR were 94.4% and
      99.3%, respectively. Thirty-nine foetuses with CT, including four deaths, were
      reported. The five PCR-negative but infected infants were identified by the
      serological and clinical follow-up program. Thirty percent of amniocenteses were
      performed in the third trimester, and gestational age or treatment did not
      influence PCR sensitivity. Amniocentesis is indicated in women with acute
      maternal infection, and facilitated targeted therapies in pregnant women and
      their offspring. In women with late toxoplasma infection, negative amniotic fluid
      PCR made treatment of infants unnecessary. Serological and clinical follow-up of
      infants is important to confirm the infection status of the infant.
      Recommendations, based on our 17-year experience, to improve the current
      diagnostic strategies and to reduce unnecessary amniocentesis, are given. 

PMID- 25596784
TI  - ESCMID guideline for the diagnosis and treatment of biofilm infections 2014.
AB  - Biofilms cause chronic infections in tissues or by developing on the surfaces of
      medical devices. Biofilm infections persist despite both antibiotic therapy and
      the innate and adaptive defence mechanisms of the patient. Biofilm infections are
      characterized by persisting and progressive pathology due primarily to the
      inflammatory response surrounding the biofilm. For this reason, many biofilm
      infections may be difficult to diagnose and treat efficiently. It is the purpose
      of the guideline to bring the current knowledge of biofilm diagnosis and therapy
      to the attention of clinical microbiologists and infectious disease specialists.
      Selected hallmark biofilm infections in tissues (e.g. cystic fibrosis with
      chronic lung infection, patients with chronic wound infections) or associated
      with devices (e.g. orthopaedic alloplastic devices, endotracheal tubes,
      intravenous catheters, indwelling urinary catheters, tissue fillers) are the main
      focus of the guideline, but experience gained from the biofilm infections
      included in the guideline may inspire similar work in other biofilm infections.
      The clinical and laboratory parameters for diagnosing biofilm infections are
      outlined based on the patient's history, signs and symptoms, microscopic
      findings, culture-based or culture-independent diagnostic techniques and specific
      immune responses to identify microorganisms known to cause biofilm infections.
      First, recommendations are given for the collection of appropriate clinical
      samples, for reliable methods to specifically detect biofilms, for the evaluation
      of antibody responses to biofilms, for antibiotic susceptibility testing and for
      improvement of laboratory reports of biofilm findings in the clinical
      microbiology laboratory. Second, recommendations are given for the prevention and
      treatment of biofilm infections and for monitoring treatment effectiveness.
      Finally, suggestions for future research are given to improve diagnosis and
      treatment of biofilm infections. 

PMID- 25596786
TI  - Transcatheter closure of a post-myocardial infarction ventricular septal rupture
      using a parachute device.

PMID- 25596787
TI  - Transcatheter lotus valve implantation in a degenerated carpentier-edwards
      bioprosthesis.

PMID- 25596788
TI  - When collateral damage does matter: iatrogenic ventricular septal rupture after
      percutaneous coronary intervention of the left anterior descending artery.

PMID- 25596785
TI  - Drinking trajectories among HIV-infected men who have sex with men: a cohort
      study of United States veterans.
AB  - BACKGROUND: Although high rates of alcohol consumption and related problems have
      been observed among HIV-infected men who have sex with men (MSM), little is known
      about the long-term patterns of and factors associated with hazardous alcohol use
      in this population. We sought to identify alcohol use trajectories and correlates
      of hazardous alcohol use among HIV-infected MSM. METHODS: Sexually active, HIV
      infected MSM participating in the Veterans Aging Cohort Study were eligible for
      inclusion. Participants were recruited from VA infectious disease clinics in
      Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh, and Washington,
      DC. Data from annual self-reported assessments and group-based trajectory models
      were used to identify distinct alcohol use trajectories over an eight-year study
      period (2002-2010). We then used generalized estimate equations (GEE) to examine
      longitudinal correlates of hazardous alcohol use (defined as an AUDIT-C score
      >=4). RESULTS: Among 1065 participants, the mean age was 45.5 (SD=9.2) and 606
      (58.2%) were African American. Baseline hazardous alcohol use was reported by 309
      (29.3%). Group-based trajectory modeling revealed a distinct group (12.5% of the
      sample) with consistently hazardous alcohol use, characterized by a mean AUDIT-C
      score of >5 at every time point. In a GEE-based multivariable model, hazardous
      alcohol use was associated with earning <$6000 annually, having an alcohol
      related diagnosis, using cannabis, and using cocaine. CONCLUSIONS: More than 1 in
      10 HIV-infected MSM US veterans reported consistent, long-term hazardous alcohol
      use. Financial insecurity and concurrent substance use were predictors of
      consistently hazardous alcohol use, and may be modifiable targets for
      intervention.

PMID- 25596789
TI  - Avulsion of an aortic cusp during aortic balloon valvuloplasty.

PMID- 25596790
TI  - Real-time ultrasound guidance facilitates transradial access: RAUST (Radial
      Artery access with Ultrasound Trial).
AB  - OBJECTIVES: This study sought to assess the utility of ultrasound (US) guidance
      for transradial arterial access. BACKGROUND: US guidance has been demonstrated to
      facilitate vascular access, but has not been tested in a multicenter randomized
      fashion for transradial cardiac catheterization. METHODS: We conducted a
      prospective multicenter randomized controlled trial of 698 patients undergoing
      transradial cardiac catheterization. Patients were randomized to needle insertion
      with either palpation or real-time US guidance (351 palpation, 347 US). Primary
      endpoints were the number of forward attempts required for access, first-pass
      success rate, and time to access. RESULTS: The number of attempts was reduced
      with US guidance [mean: 1.65 +/- 1.2 vs. 3.05 +/- 3.4, p < 0.0001; median: 1
      (interquartile range [IQR]: 1 to 2) vs. 2 (1 to 3), p < 0.0001] and the first
      pass success rate improved (64.8% vs. 43.9%, p < 0.0001). The time to access was
      reduced (88 +/- 78 s vs. 108 +/- 112 s, p = 0.006; median: 64 [IQR: 45 to 94] s
      vs. 74 [IQR: 49 to 120] s, p = 0.01). Ten patients in the control group required
      crossover to US guidance after 5 min of failed palpation attempts with 8 of 10
      (80%) having successful sheath insertion with US. The number of difficult access
      procedures was decreased with US guidance (2.4% vs. 18.6% for >=5 attempts, p <
      0.001; 3.7% vs. 6.8% for >=5min, p = 0.07). No significant differences were
      observed in the rate of operator-reported spasm, patient pain scores following
      the procedure, or bleeding complications. CONCLUSIONS: Ultrasound guidance
      improves the success and efficiency of radial artery cannulation in patients
      presenting for transradial catheterization. (Radial Artery Access With Ultrasound
      Trial [RAUST]; NCT01605292).

PMID- 25596791
TI  - Inferior vena cava filter thrombosis and suprarenal caval stenosis: a double
      whammy.

PMID- 25596793
TI  - First-in-man use of intravascular near-infrared spectroscopy in the carotid
      arteries to characterize atherosclerotic plaque prior to carotid stenting.

PMID- 25596792
TI  - Efficacy of polymer injection for ischemic mitral regurgitation: persistent
      reduction of mitral regurgitation and attenuation of left ventricular remodeling.
AB  - OBJECTIVES: The aim of this study was to examine the chronic effects of polyvinyl
      alcohol (PVA) injection on mitral regurgitation (MR) reduction, mitral valve
      geometry, and left ventricular (LV) remodeling in a chronic ischemic MR sheep
      model. BACKGROUND: Previous studies have demonstrated acute efficacy of PVA
      hydrogel polymer injection into infarcted myocardium underlying the papillary
      muscle to relieve MR by papillary muscle repositioning. However, the chronic
      efficacy of PVA injection in the chronic infarction setting remains unclear.
      METHODS: Sixteen sheep developed chronic MR 8 weeks after induced inferoposterior
      myocardial infarction. Ten consecutive sheep underwent PVA injection (PVA group)
      and 6 sheep served as control subjects with saline injection. Epicardial 2-/3
      dimensional echocardiography was performed at the baseline, chronic MR (pre
      injection), and sacrifice (8 weeks after injection) stages. RESULTS: Both groups
      were comparable at the baseline and chronic MR stages. At sacrifice, MR decreased
      from moderate to trace or mild (vena contracta: 0.17 +/- 0.08 cm vs. 0.56 +/-
      0.10 cm, p < 0.001) in the PVA group but progressed to moderate to severe in the
      control group. End-systolic and -diastolic volumes remained stable in the PVA
      group but increased significantly in the control group (both p < 0.05). At
      sacrifice, compared with the control group, the PVA group had significantly less
      left ventricular remodeling (end-systolic volume: 41.1 +/- 10.4 ml vs. 55.9 +/-
      12.4 ml, p < 0.05), lower MR severity (vena contracta: 0.17 +/- 0.08 cm vs. 0.60
      +/- 0.14 cm, p < 0.01), and favorable changes in mitral valve geometry.
      CONCLUSIONS: Polymer injection in a chronic ischemic MR model results in
      persistent reduction of MR and attenuation of continued left ventricular
      remodeling over 8 weeks of follow-up.

PMID- 25596794
TI  - Alice in Wonderland syndrome and hypermobility of the temporomandibular joint:
      association or coincidence?

PMID- 25596795
TI  - Limited mouth opening of unknown cause cured by diagnostic coronoidectomy: a new
      clinical entity?
AB  - Limited mouth opening is a constant annoyance and can be life-threatening should
      intubation be needed. The causes are numerous and are categorised as intra
      articular or extra-articular, which are often difficult to distinguish. We
      present what we regard as a new clinical entity - long-standing limited mouth
      opening of unknown cause - and describe our treatment. Four female patients
      presented with limited mouth opening and lateral and protrusive movements within
      normal limits, which were typical of restriction of extra-articular origin.
      However, the radiological findings were within normal limits, with no visible
      cause of the restriction. All four were treated by bilateral coronoidectomy that
      resulted in the immediate return of mouth opening to within normal limits that
      was preserved over subsequent years. Histopathological examination showed atrophy
      and degenerative changes in the temporalis band that had been attached to the
      coronoid, which accounts for the stiffness of the temporalis muscle but does not
      explain the pathogenesis. In the light of this "diagnostic coronoidectomy"
      further studies are required to document the underlying pathological changes and
      to develop more accurate imaging that will enable correct diagnosis in future.

PMID- 25596796
TI  - Oral and maxillofacial surgery in medical schools in the United Kingdom.
AB  - It has been suggested that oral and maxillofacial surgery (OMFS) is better
      established in dental schools than in medical schools, and as a result, dental
      students have a greater insight into the scope of the specialty. We explore how
      much time is allocated to OMFS in the undergraduate curriculum in medical schools
      in the UK, and the students' perceptions of the specialty. A total of 186 final
      year students from 5 medical schools were recruited in a questionnaire-based
      survey. Of them, 141 (76%) reported no exposure to OMFS, and 37 of the 45
      students (82%) who had had some exposure reported that it was not part of their
      timetabled curriculum. The 2 aspects considered most important by students were
      the long training pathway (n=38, 20%) and the requirement for dual qualification
      (n=33, 18%). Our results suggest that UK medical schools provide limited exposure
      to OMFS. We think it is important that the specialty is included in the
      compulsory undergraduate curriculum to ensure that medical students gain some
      awareness. This will not only allow junior doctors to make better informed
      decisions about their chosen careers, but may also help to reduce the number of
      inappropriate referrals from doctors in other specialties.

PMID- 25596797
TI  - Integration of a prognostic gene module with a drug sensitivity module to
      identify drugs that could be repurposed for breast cancer therapy.
AB  - BACKGROUND: Efficiently discovering low risk drugs is important for drug
      development. However, the heterogeneity in patient population complicates the
      prediction of the therapeutic efficiency. Drug repositioning aiming to discover
      new indications of known drugs provides a possible gateway. METHOD: We introduce
      a novel computational method to identify suitable drugs by using prognosis
      information of patients. First, we identify prognostic related gene modules,
      Prognostic Gene Ontology Module (PGOMs), by incorporating multiple functional
      annotations. Then, we build the drug sensitivity modules based on gene
      expressions and drug activity patterns. Finally, we analyze the potential effects
      of drugs on prognostic gene modules and establish the links between PGOMs and
      drugs. RESULT AND DISCUSSION: With PGOMs generated based on the patient outcome,
      FDA approved drugs for breast cancer treatment have been successfully identified
      on one hand; several drugs that have not been approved by FDA, such as Etoposide,
      have found to strongly associate with the outcome on the other hand. With PGOMs
      generated based on the patient ER status, Tamoxifen and Exemestane rank at the
      top of the drug list, suggesting that they may be more specific to ER status of
      breast cancer. Especially, the rank difference of Exemestane in ER+ group and ER-
      group is very large, demonstrating that Exemestane may be more specific to ER+
      breast cancer and would cause side-effect to ER- breast cancer patients. Our
      method can not only identify the drugs that could be repurposed for breast cancer
      therapy, but also can reveal their effective pharmacological mechanisms.

PMID- 25596798
TI  - One final word....

PMID- 25596799
TI  - Ventricular assist devices: The future is now.
AB  - Heart failure has become a global epidemic. For advanced heart failure, a broad
      assortment of device options have been introduced for both acute and prolonged
      intervals of hemodynamic assistance. Durable implantable ventricular assist
      devices (VADs) in particular play a key role in the management of advanced heart
      failure. This review focuses specifically on the current outcomes with VAD
      therapy, highlights the results from pivotal clinical trials, and summarizes the
      various device options on the market and those in preclinical development. 

PMID- 25596800
TI  - Familial pulmonary fibrosis.
AB  - The occurrence of pulmonary fibrosis in numerous individuals from the same family
      suggests a genetic cause for the disease. During the last 10 years, mutations
      involving proteins from the telomerase complex and from the surfactant system
      have been identified in association with pulmonary fibrosis. Mutations of TERT,
      the coding gene for the telomerase reverse transcriptase, are the most frequently
      identified mutations and are present in 15% of cases of familial pulmonary
      fibrosis. Other mutations (TERC, surfactant proteins genes) are only rarely
      evidenced in adults. Patients with mutations involving the telomerase complex may
      present with pulmonary fibrosis, hematologic, cutaneous or liver diseases. Other
      genetic variations associated with pulmonary fibrosis such as a polymorphism in
      the promoter of MUC5B or a polymorphism in TERT have been recently described, and
      could be considered to be part of a polygenic transmission. Evidence for
      mutations associated with the development of pulmonary fibrosis raises numerous
      clinical questions from establishing a diagnosis, providing counselling to
      deciding on therapy, and requires specific studies. From a pathophysiological
      point of view, the function of the genes highlights the central role of alveolar
      epithelium and aging in fibrogenesis.

PMID- 25596801
TI  - Trying to remember: immunological B cell memory to malaria.
AB  - In areas with stable transmission of Plasmodium falciparum parasites, even
      partially-protective immunity to malaria is acquired only after years of exposure
      and several infections. It has long been speculated that malaria parasites are
      directly able to undermine the establishment and maintenance of immunological
      memory, and that the often transient antibody responses to this parasite are
      evidence of such a dysfunction. We propose that long-lived antibody responses may
      not always be a prerequisite for protection, and that antibody longevity varies
      in an exposure- and age-dependent manner. 

PMID- 25596802
TI  - Improving transparency of clinical trials.
AB  - Recent data reveal that subtle selective publication affects critical aspects of
      trial reporting, in some cases altering the interpretation of results. Timely
      prospective registration could help deter selective reporting and clinical trial
      stakeholders from government authorities to journal editors should work together
      to foster prospective registration of trials. 

PMID- 25596803
TI  - Bovine fasciolosis: control strategies based on the location of Galba truncatula
      habitats on farms.
AB  - Infection of livestock with Fasciola hepatica is a worldwide, economically
      important and increasing problem. Even though, bovine fasciolosis can be a
      disease associated with particular regions, there are usually epidemiological
      issues on individual farms. For this reason, it is recommended to find the source
      of infection by examination of definite hosts and pastures on a farm. The
      following factors which promote the transmission of bovine fasciolosis are
      usually found: (A) Snail habitats are present on pastures used for young stock
      (prior to first calving) or dry cows only. Pastures for dairy cows are not
      affected. (B) Snail habitats are present on all pastures for dairy cows. (C)
      Snail habitats are present on single pastures used for dairy cows. (D) Snail
      habitats are present on hayfields. For each of these epidemiological situations
      an individual control strategy is advised. When a control strategy is tailored
      according to the specific epidemiology found on the individual farm, egg shedding
      and F. hepatica-seroprevalence can be reduced significantly. This approach can
      support the responsible use of the available flukicides.

PMID- 25596804
TI  - The first autochthonous case of human melioidosis in Reunion Island.

PMID- 25596806
TI  - A catalytic triad--Lys-Asn-Asp--Is essential for the catalysis of the methyl
      transfer in plant cation-dependent O-methyltransferases.
AB  - Crystal structure data of cation-dependent catechol O-methyltransferases (COMTs)
      from mammals and related caffeoyl coenzyme A OMTs (CCoAOMTs) from plants have
      suggested operative molecular mechanisms. These include bivalent cations that
      facilitate deprotonation of vicinal aromatic dihydroxy systems and illustrate a
      conserved arrangement of hydroxyl and carboxyl ligands consistent with the
      requirements of a metal-activated catalytic mechanism. The general concept of
      metal-dependent deprotonation via a complexed aspartate is only one part of a
      more pronounced proton relay, as shown by semiempirical and DFT quantum
      mechanical calculations and experimental validations. A previously undetected
      catalytic triad, consisting of Lys157-Asn181-Asp228 residues is required for
      complete methyl transfer in case of a cation-dependent phenylpropanoid and
      flavonoid OMT, as described in this report. This triad appears essential for
      efficient methyl transfer to catechol-like hydroxyl group in phenolics. The
      observation is consistent with a catalytic lysine in the case of mammalian COMTs,
      but jettisons existing assumptions on the initial abstraction of the meta
      hydroxyl proton to the metal stabilizing Asp154 (PFOMT) or comparable Asp
      carboxyl groups in type of cation-dependent enzymes in plants. The triad is
      conserved among all characterized plant CCoAOMT-like enzymes, which are required
      not only for methylation of soluble phenylpropanoids like coumarins or monolignol
      monomers, but is also present in the similar microbial and mammalian cation
      dependent enzymes which methylate a comparable set of substrates. 

PMID- 25596805
TI  - Cytotoxic and natural killer cell stimulatory constituents of Phyllanthus
      songboiensis.
AB  - A dichapetalin-type triterpenoid and a dibenzylbutyrolactone-type lignan,
      together with five known lignans, a known aromatic diterpenoid, and a known
      acylated phytosterol, were isolated from the aerial parts of Phyllanthus
      songboiensis, collected in Vietnam. Their structures were determined by
      interpretation of the spectroscopic data, and the inhibitory activity toward HT
      29 human colon cancer cells of all isolates was evaluated by a cytotoxicity
      assay. The known arylnaphthalene lignan, (+)-acutissimalignan A, was highly
      cytotoxic toward HT-29 cells, with an IC50 value of 19 nM, but this compound was
      inactive as a DNA topoisomerase IIalpha (topo IIalpha) poison. The known
      phytosterol, (-)-beta-sitosterol-3-O-beta-D-(6-O-palmitoyl)glucopyranoside, was
      found to stimulate natural killer (NK) cells at a concentration of 10MUM in the
      presence of interleukin 12 (IL-12).

PMID- 25596807
TI  - Molecular mechanisms of constitutive and inducible NF-kappaB activation in
      oesophageal adenocarcinoma.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) regulates the expression of a large
      number of genes involved in the immune and inflammatory response. NF-kappaB is
      constitutively activated in oesophageal tumour tissues and induced in oesophageal
      cells by bile and acid. The aim of the present study was to define the mechanisms
      underlying NF-kappaB activation in oesophageal adenocarcinoma. PATIENTS AND
      METHODS: Fresh biopsy specimens were obtained from 20 patients with oesophageal
      adenocarcinoma. The activation of NF-kappaB in oesophageal tumour specimens and
      oesophageal SKGT-4 cells was assessed by gel mobility shift and Western blotting.
      Phosphorylation of protein kinase B (AKT/PKB), Ikappa kinase-alpha/beta (IKK
      alpha/beta) and extracellular signal-regulated kinase 1/2 (ERK1/2) was examined
      by Western blotting. High content analysis was used to quantify NF-kappaB
      translocation in oesophageal cells. RESULTS: Oesophageal tumour tissues had
      higher levels of NF-kappaB. Increased levels of phosphorylated AKT and IKK
      alpha/beta and ERK1/2 were detected in tumour tissues compared with normal
      oesophageal mucosa. Exposure of SKGT-4 cells to deoxycholic acid (DCA) or acid
      resulted in NF-kappaB activation and phosphorylation of AKT, IKK-alpha/beta and
      ERK1/2. Specific inhibitors for phosphoinositide 3-kinase; PI3K (LY294002 and
      worhmannin) and ERK1/2 inhibitors (PD98059 and U0126) suppressed DCA- and acid
      induced NF-kappaB activation. The proteasome inhibitor MG-132 and the
      antioxidants vitamin C and pyrrolidine dithiocarbamate (PDTC) also inhibited NF
      kappaB activation. CONCLUSIONS: Our data demonstrate a major role for PI3K/AKT
      IKK-alpha/beta-ERK1/2 signalling pathway in NF-kappaB activation in oesophageal
      adenocarcinoma. These results suggest that NF-kappaB may be a prognostic marker
      for oesophageal adenocarcinoma, and modulating of NF-kappaB may uncover new
      therapeutic strategies.

PMID- 25596809
TI  - [Vaccination status of immunocompromised patients attended in primary care].

PMID- 25596808
TI  - Self-administered outpatient parenteral antimicrobial therapy (S-OPAT) for
      infective endocarditis: a safe and effective model.
AB  - The safety and efficacy of treatment of infectious endocarditis (IE) was
      evaluated within a program of hospital-in-home (HIH) based on self-administered
      outpatient parenteral antimicrobial therapy (S-OPAT). IE episodes (n=48 in 45
      patients; 71% middle-aged males) were recruited into the HIH program between 1998
      and 2012. Following treatment stabilization at the hospital they returned home
      for HIH in which a physician and/or a nurse supervised the S-OPAT. Safety and
      efficacy were evaluated as mortality, re-occurrence, and unexpected re-admission
      to hospital. Of the episodes of IE, 83.3% had comorbidities with a mean score of
      2.3 on the Charlson index and 1.5 on the Profund index; 60.4% had pre-existing
      valve disease (58.6% having had surgical intervention); 8.3% of patients had
      suffered a previous IE episode; 62.5% of all episodes affected a native valve;
      45.8% being mitral; 70.8% of infection derived from the community. In 75% of the
      episodes there was micro-organism growth, of which 83.3% were Gram positive.
      Overall duration of antibiotic treatment was 4.8 weeks; 60.4% of this time
      corresponding to HIH. Re-admission occurred in 12.5% of episodes of which 33.3%
      returned to HIH to complete the S-OPAT. No deaths occurred during HIH. One year
      after discharge, 2 patients had recurrence and 5 patients died, in 2 of whom
      previous IE as cause-of-death could not be excluded. In conclusion, the S-OPAT
      schedule of hospital-in-home is safe and efficacious in selected patients with
      IE.

PMID- 25596810
TI  - Surgical treatment of scoliosis in Rubinstein-Taybi syndrome type 2: a case
      report.
AB  - INTRODUCTION: Rubinstein-Taybi syndrome is an autosomal dominant disorder
      resulting in congenital craniofacial deformities, and divided into types 1 and 2.
      Scoliosis has not been reported as one of the extra-cranial manifestations of
      Rubinstein-Taybi syndrome type 2. CASE PRESENTATION: We present a 14-year-old
      British Caucasian girl with Rubinstein-Taybi type 2 syndrome who developed a
      severe double thoracic scoliosis measuring 39 degrees  and 68 degrees 
      respectively. Her scoliosis was associated with thoracic hypokyphosis, causing a
      marked reduction in the anteroposterior diameter of her chest and consequent
      severe restrictive lung disease. The deformity was noted by her local
      pediatrician as part of a chest infection assessment when she was aged 13 years,
      and gradually progressed as the result of spinal growth. Our patient underwent a
      posterior spinal arthrodesis using a single concave pedicle hook and screw rod
      construct and locally harvested autologous graft supplemented by allograft bone.
      This spinal fixation technique was selected because of our patient's low body
      weight to avoid prominence of the instrumentation causing skin healing problems
      and pain. Her scoliosis was corrected to 18 degrees  and 30 degrees  and we
      achieved a balanced spine in the coronal and sagittal planes. An underarm spinal
      jacket was provided for six months after surgery. During her latest follow-up at
      skeletal maturity, our patient had an excellent cosmetic outcome with no loss of
      deformity correction or detected pseudoarthrosis and a normal level of
      activities. CONCLUSION: Scoliosis can develop in young children with Rubinstein
      Taybi syndrome type 2, with the deformity deteriorating around the pubertal
      growth spurt. Surgical treatment can correct the deformity, balance the spine and
      prevent mechanical back pain. It can also stabilize the chest area and avoid
      respiratory complications developing as the scoliosis progresses, which can
      result in severe restrictive pulmonary disease. The use of single concave
      instrumentation is indicated in very slim patients with poor muscle bulk; in our
      patient, this produced satisfactory deformity correction and a favorable outcome
      at completion of growth. Peri-operative care in this group of patients can be
      very challenging because of associated co-morbidities as well as the presence of
      severe behavioral issues that result in poor patient compliance.

PMID- 25596811
TI  - Vitiligo.
AB  - Vitiligo, an acquired pigmentary disorder of unknown origin, is the most frequent
      cause of depigmentation worldwide, with an estimated prevalence of 1%. The
      disorder can be psychologically devastating and stigmatising, especially in dark
      skinned individuals. Vitiligo is clinically characterised by the development of
      white macules due to the loss of functioning melanocytes in the skin or hair, or
      both. Two forms of the disease are well recognised: segmental and non-segmental
      vitiligo (the commonest form). To distinguish between these two forms is of prime
      importance because therapeutic options and prognosis are quite different. The
      importance of early treatment and understanding of the profound psychosocial
      effect of vitiligo will be emphasised throughout this Seminar. 

PMID- 25596812
TI  - Leptin disturbance probably involved in the pathogenesis of obesity-induced
      depressive symptoms.

PMID- 25596813
TI  - Lower urinary tract symptoms and falls in older women: a case control study.
AB  - OBJECTIVES: To examine the distribution of lower urinary tract symptoms (LUTS) in
      women >65y old presenting to the emergency department following a fall or fall
      related injury. STUDY DESIGN: A prospective, case controlled postal questionnaire
      study. SETTING: University Teaching Hospital, London, UK. MAIN OUTCOME MEASURES:
      The distribution of LUTS were assessed using the International Consultation on
      Incontinence Modular Questionnaire for female lower urinary tract symptoms. Data
      were analysed using descriptive statistics to determine whether there was a
      difference in the distribution of LUTS between women presenting with a fall or
      non-fall related health problem. The proportion of women who attributed their
      fall to lower urinary tract symptoms was also assessed. RESULTS: No difference in
      the distribution of LUTS was found between older women presenting with a fall and
      those without. Only 6.5% of women presenting with falls attributed their fall to
      antecedent LUTS. CONCLUSION: No relationship between falls and urgency or urgency
      incontinence was found in a cohort of older women presenting to the emergency
      department having fallen. A temporal association between falls and LUTS was
      observed in only a minority of falls.

PMID- 25596814
TI  - Uses of anti-Mullerian hormone (AMH) measurement before and after cancer
      treatment in women.
AB  - There is a growing body of evidence supporting the use of anti-Mullerian hormone
      (AMH) serum levels as a biomarker of the growing follicle pool, in turn taken to
      reflect the ovarian reserve, in patients being treated for cancer. Many cancer
      therapies are gonadotoxic, often inducing premature ovarian insufficiency (POI)
      and thus rendering such patients infertile. The degree of ovariotoxicity is
      related to the type of treatment, dosage and patient's age. As survival rates
      from cancer improve, post-treatment reproductive health is becoming increasingly
      important to affected girls and women of reproductive age to allow them to have
      biologically-related children. AMH levels taken post-treatment may be able to
      guide advice regarding remaining reproductive lifespan and aid decision-making on
      suitable adjuvant hormonal treatments such as in hormone receptor-positive breast
      cancer. Furthermore, pre-treatment AMH levels are now shown to be predictive of
      long-term ovarian function. The development of prognostic scoring and
      classification methods including the use of pre-treatment AMH, as well as other
      patient factors including age, to determine the likelihood of return of menses
      may allow better individualisation of advice regarding the use of fertility
      preservation strategies prior to commencing cancer treatment. AMH may also be a
      useful marker of cancer therapy-related ovarian damage in pre-pubertal children,
      although there are very limited data on the relationship between AMH and the
      ovarian reserve in children and adolescents. AMH is proving to be of increasing
      value in assessing ovarian function and advising patients before and after cancer
      treatment. 

PMID- 25596815
TI  - Vulvo-vaginal atrophy: a new treatment modality using thermo-ablative fractional
      CO2 laser.
AB  - OBJECTIVE: To evaluate the efficacy and feasibility of thermo-ablative fractional
      CO2 laser for the treatment of symptoms related to vulvo-vaginal atrophy (VVA) in
      post-menopausal women. METHODS: From April 2013 to December 2013, post-menopausal
      patients who complained of one or more VVA-related symptoms and who underwent
      vaginal treatment with fractional CO2 laser were enrolled in the study. At
      baseline (T0) and 30 days post-treatment (T1), vaginal status of the women was
      evaluated using the Vaginal Health Index (VHI), and subjective intensity of VVA
      symptoms was evaluated using a visual analog scale (VAS). At T1, treatment
      satisfaction was evaluated using a 5-point Likert scale. RESULTS: During the
      study period, a total of 48 patients were enrolled. Data indicated a significant
      improvement in VVA symptoms (vaginal dryness, burning, itching and dyspareunia)
      (P<0.0001) in patients who had undergone 3 sessions of vaginal fractional CO2
      laser treatment. Moreover, VHI scores were significantly higher at T1 (P<0.0001).
      Overall, 91.7% of patients were satisfied or very satisfied with the procedure
      and experienced considerable improvement in quality of life (QoL). No adverse
      events due to fractional CO2 laser treatment occurred. CONCLUSION: Thermo
      ablative fractional CO2 laser could be a safe, effective and feasible option for
      the treatment of VVA symptoms in post-menopausal women.

PMID- 25596816
TI  - Perceived barriers to healthcare for persons living in poverty in Quebec, Canada:
      the EQUIhealThY project.
AB  - INTRODUCTION: Ensuring access to timely and appropriate primary healthcare for
      deprived patients is an issue facing all countries, even those with universal
      healthcare systems. There is a paucity of information on how patients living in a
      context of material and social deprivation perceive barriers in the healthcare
      system. This study combines the perspectives of persons living in poverty and of
      healthcare providers to explore barriers to responsive care for underserved
      persons with a view to developing equity-focused primary care. METHODS: In this
      participatory action research we used photovoice, together with a method known as
      'merging of knowledge and practice' developed by ATD Fourth World, an
      international community organization working to eradicate poverty. The study was
      conducted in two teaching primary care practices in the Canadian province of
      Quebec. Participants consisted of 15 health professionals and six members of ATD
      Fourth World; approximately 60 group meetings were held. Data were analyzed
      through thematic analysis, in part with the involvement of persons living in
      poverty. RESULTS: Three main barriers to responsive care in a context of poverty
      were highlighted by all participants: the difficult living conditions of people
      living in poverty, the poor quality of interactions between providers and
      underserved patients, and the complexity of healthcare system organization and
      functioning. CONCLUSION: Our research revealed that unhealthy living conditions
      prevent persons living in poverty from accessing quality healthcare and
      maintaining good health. Also, the complexity of the healthcare system's
      organization and functioning has a negative impact on the interactions with
      healthcare providers. Changes in policy and practice are needed to address those
      barriers and to achieve greater equity and provide more responsive care for
      persons living in poverty.

PMID- 25596817
TI  - Role of extracytoplasmic function sigma factors in biofilm formation of
      Porphyromonas gingivalis.
AB  - BACKGROUND: Porphyromonas gingivalis has been implicated as a major pathogen in
      the development and progression of chronic periodontitis. P. gingivalis biofilm
      formation in the subgingival crevice plays an important role in the ability of
      the bacteria to tolerate stress signals outside the cytoplasmic membrane. Some
      bacteria use a distinct subfamily of sigma factors to regulate their
      extracytoplasmic functions (the ECF subfamily). The objective of this study was
      to determine if P. gingivalis ECF sigma factors affect P. gingivalis biofilm
      formation. METHODS: To elucidate the role of ECF sigma factors in P. gingivalis,
      chromosomal mutants carrying a disruption of each ECF sigma factor-encoding gene
      were constructed. Bacterial growth curves were measured by determining the
      turbidity of bacterial cultures. The quantity of biofilm growing on plates was
      evaluated by crystal violet staining. RESULTS: Comparison of the growth curves of
      wild-type P. gingivalis strain 33277 and the ECF mutants indicated that the
      growth rate of the mutants was slightly lower than that of the wild-type strain.
      The PGN_0274- and PGN_1740-defective mutants had increased biofilm formation
      compared with the wild-type (p < 0.001); however, the other ECF sigma factor
      mutants or the complemented strains did not enhance biofilm formation.
      CONCLUSION: These results suggest that PGN_0274 and PGN_1740 play a key role in
      biofilm formation by P. gingivalis.

PMID- 25596818
TI  - Overview of neuropathy associated with taxanes for the treatment of metastatic
      breast cancer.
AB  - Taxanes are an established option in the standard treatment paradigm for patients
      with metastatic breast cancer (MBC). Neuropathy is a common, dose-limiting side
      effect of taxane therapy that is often managed by dose reductions and delays. The
      severity, time to onset, and improvement in neuropathy are important
      considerations for patient management and vary among currently approved taxanes.
      The rate of grade >=3 neuropathy with taxanes has been shown to be dose and
      schedule dependent; however, time to improvement to grade <=1 is typically
      shorter for nab-paclitaxel than for other taxanes in patients with MBC. Many
      tools for assessing patient-reported neuropathy exist. Because MBC is incurable
      and patient quality of life must be critically considered when making treatment
      decisions, there is a need for more prospective trials to assess patient-reported
      neuropathy. Validated predictors of taxane-related neuropathy may play an
      important role in treatment decisions in the future. This review will focus on
      the toxicity profile (i.e., neuropathy) of each of the taxanes used in the
      treatment of MBC, will provide updates on tools used for the assessment of
      neuropathy, and will highlight newly discovered predictors of taxane-related
      neuropathy. 

PMID- 25596819
TI  - Aging-dependent alterations in gene expression and a mitochondrial signature of
      responsiveness to human influenza vaccination.
AB  - To elucidate gene expression pathways underlying age-associated impairment in
      influenza vaccine response, we screened young (age 21-30) and older (age>=65)
      adults receiving influenza vaccine in two consecutive seasons and identified
      those with strong or absent response to vaccine, including a subset of older
      adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0)
      and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene
      expression microarray analysis. We defined a response signature and also detected
      induction of a type I interferon response at day 2 and a plasma cell signature at
      day 7 post-vaccine in young responders. The response signature was dysregulated
      in older adults, with the plasma cell signature induced at day 2, and was never
      induced in frail subjects (who were all non-responders). We also identified a
      mitochondrial signature in young vaccine responders containing genes mediating
      mitochondrial biogenesis and oxidative phosphorylation that was consistent in two
      different vaccine seasons and verified by analyses of mitochondrial content and
      protein expression. These results represent the first genome-wide transcriptional
      profiling analysis of age-associated dynamics following influenza vaccination,
      and implicate changes in mitochondrial biogenesis and function as a critical
      factor in human vaccine responsiveness.

PMID- 25596820
TI  - Sex-specific recombination maps for individual macrochromosomes in the Japanese
      quail (Coturnix japonica).
AB  - Meiotic recombination in the Japanese quail was directly studied by
      immunolocalization of mutL homolog 1 (MLH1), a mismatch repair protein of mature
      recombination nodules. In total, 15,862 crossovers were scored along the
      autosomal synaptonemal complexes in 308 meiotic nuclei from males and females.
      Crossover frequencies calculated from MLH1 foci show wide similitude between
      males and females with slightly higher number of foci in females. From this
      analysis, we predict that the sex-averaged map length of the Japanese quail is
      2580 cM, with a genome-wide recombination rate of 1.9 cM/Mb. MLH1 focus mapping
      along the six largest bivalents showed few intersex differences in the
      distribution of crossovers along with variant patterns in metacentric and
      acrocentric macrobivalents. These results provide valuable information to
      complement linkage map analysis in the species while providing insight into our
      understanding of the mechanisms of crossover distribution along chromosome arms. 

PMID- 25596821
TI  - Engineering of plant chromosomes.
AB  - Engineered minimal chromosomes with sufficient mitotic and meiotic stability have
      an enormous potential as vectors for stacking multiple genes required for complex
      traits in plant biotechnology. Proof of principle for essential steps in
      chromosome engineering such as truncation of chromosomes by T-DNA-mediated
      telomere seeding and de novo formation of centromeres by cenH3 fusion protein
      tethering has been recently obtained. In order to generate robust protocols for
      application in plant biotechnology, these steps need to be combined and
      supplemented with additional methods such as site-specific recombination for the
      directed transfer of multiple genes of interest on the minichromosomes. At the
      same time, the development of these methods allows new insight into basic aspects
      of plant chromosome functions such as how centromeres assure proper distribution
      of chromosomes to daughter cells or how telomeres serve to cap the chromosome
      ends to prevent shortening of ends over DNA replication cycles and chromosome end
      fusion. 

PMID- 25596823
TI  - Advances in genetic modification of farm animals using zinc-finger nucleases
      (ZFN).
AB  - Genome editing tools (GET), including zinc-finger nucleases (ZFN), transcription
      activator-like endonucleases (TALENS), and meganucleases possess long recognition
      sites and are thus capable of cutting DNA in a very specific manner. These genome
      editing tools mediate targeted genetic alterations by enhancing DNA mutation
      frequency via induction of double-strand breaks at a predetermined genomic site.
      Compared to conventional homologous recombination based gene targeting, GETs can
      increase gene targeting and gene disruption via mutagenic DNA repair more than
      10,000-fold. Recently, a novel class of genome editing tools was described that
      uses RNAs to target a specific genomic site. The CRISPR/Cas9 system is capable of
      targeting even multiple genomic sites in one shot and thus could be superior to
      ZFNs or TALEN. Current results indicate that these tools can be successfully
      employed in a broad range of organisms which renders them useful for improving
      the understanding of complex physiological systems, producing transgenic animals,
      including creating large animal models for human diseases, creating specific cell
      lines, and plants, and even for treating human genetic diseases. This review
      provides an update on the use of ZFNs to modify the genome of farm animals,
      summarizes current knowledge on the underlying mechanism, and discusses new
      opportunities for generating genetically modified farm animals. 

PMID- 25596822
TI  - Understanding the DNA damage response in order to achieve desired gene editing
      outcomes in mosquitoes.
AB  - Mosquitoes are high-impact disease vectors with the capacity to transmit
      pathogenic agents that cause diseases such as malaria, yellow fever, chikungunya,
      and dengue. Continued growth in knowledge of genetic, molecular, and
      physiological pathways in mosquitoes allows for the development of novel control
      methods and for the continued optimization of existing ones. The emergence of
      site-specific nucleases as genomic engineering tools promises to expedite
      research of crucial biological pathways in these disease vectors. The utilization
      of these nucleases in a more precise and efficient manner is dependent upon
      knowledge and manipulation of the DNA repair pathways utilized by the mosquito.
      While progress has been made in deciphering DNA repair pathways in some model
      systems, research into the nature of the hierarchy of mosquito DNA repair
      pathways, as well as in mechanistic differences that may exist, is needed. In
      this review, we will describe progress in the use of site-specific nucleases in
      mosquitoes, along with the hierarchy of DNA repair in the context of mosquito
      chromosomal organization and structure, and how this knowledge may be manipulated
      to achieve precise chromosomal engineering in mosquitoes. 

PMID- 25596825
TI  - Engineered minichromosomes in plants.
AB  - Engineered minichromosomes have been produced in several plant species via
      telomere-mediated chromosomal truncation. This approach bypasses the
      complications of the epigenetic nature of centromere function in plants, which
      has to date precluded the production of minichromosomes by the re-introduction of
      centromere sequences to a plant cell. Genes to be added to a cleaved chromosome
      are joined together with telomere repeats on one side. When these constructs are
      introduced into plant cells, the genes are ligated to the broken chromosomes but
      the telomere repeats will catalyze the formation of a telomere on the other end
      cutting the chromosome at that point. Telomere-mediated chromosomal truncation is
      sufficiently efficient that very small chromosomes can be generated consisting of
      basically the endogenous centromere and the added transgenes. The added
      transgenes provide a platform onto which it should be possible to assemble a
      synthetic chromosome to specification. Combining engineered minichromosomes with
      doubled haploid breeding should greatly expedite the transfer of transgenes to
      new lines and to test the interaction of transgenes in new background genotypes.
      Potential basic and applied applications of synthetic chromosomes are discussed. 

PMID- 25596824
TI  - Genome engineering in cattle: recent technological advancements.
AB  - Great strides in technological advancements have been made in the past decade in
      cattle genome engineering. First, the success of cloning cattle by somatic cell
      nuclear transfer (SCNT) or chromatin transfer (CT) is a significant advancement
      that has made obsolete the need for using embryonic stem (ES) cells to conduct
      cell-mediated genome engineering, whereby site-specific genetic modifications can
      be conducted in bovine somatic cells via DNA homologous recombination (HR) and
      whereby genetically engineered cattle can subsequently be produced by animal
      cloning from the genetically modified cells. With this approach, a chosen bovine
      genomic locus can be precisely modified in somatic cells, such as to knock out
      (KO) or knock in (KI) a gene via HR, a gene-targeting strategy that had almost
      exclusively been used in mouse ES cells. Furthermore, by the creative application
      of embryonic cloning to rejuvenate somatic cells, cattle genome can be
      sequentially modified in the same line of somatic cells and complex genetic
      modifications have been achieved in cattle. Very recently, the development of
      designer nucleases-such as zinc finger nucleases (ZFNs) and transcription
      activator-like effector nuclease (TALENs), and clustered regularly interspaced
      short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-has enabled
      highly efficient and more facile genome engineering in cattle. Most notably, by
      employing such designer nucleases, genomes can be engineered at single-nucleotide
      precision; this process is now often referred to as genome or gene editing. The
      above achievements are a drastic departure from the traditional methods of
      creating genetically modified cattle, where foreign DNAs are randomly integrated
      into the animal genome, most often along with the integrations of bacterial or
      viral DNAs. Here, I review the most recent technological developments in cattle
      genome engineering by highlighting some of the major achievements in creating
      genetically engineered cattle for agricultural and biomedical applications. 

PMID- 25596826
TI  - Strategies for cloning and manipulating natural and synthetic chromosomes.
AB  - Advances in synthetic biology methods to assemble and edit DNA are enabling
      genome engineering at a previously impracticable scale and scope. The synthesis
      of the Mycoplasma mycoides genome followed by its transplantation to convert a
      related cell into M. mycoides has transformed strain engineering. This approach
      exemplifies the combination of newly emerging chromosome-scale genome editing
      strategies that can be defined in three main steps: (1) chromosome acquisition
      into a microbial engineering platform, (2) alteration and improvement of the
      acquired chromosome, and (3) installation of the modified chromosome into the
      original or alternative organism. In this review, we outline recent progress in
      methods for acquiring chromosomes and chromosome-scale DNA molecules in the
      workhorse organisms Bacillus subtilis, Escherichia coli, and Saccharomyces
      cerevisiae. We present overviews of important genetic strategies and tools for
      each of the three organisms, point out their respective strengths and weaknesses,
      and highlight how the host systems can be used in combination to facilitate
      chromosome assembly or engineering. Finally, we highlight efforts for the
      installation of the cloned/altered chromosomes or fragments into the target
      organism and present remaining challenges in expanding this powerful experimental
      approach to a wider range of target organisms. 

PMID- 25596827
TI  - TALEN-mediated genome engineering to generate targeted mice.
AB  - Genetic mouse models are critical for biomedical research to understand gene
      function and pathophysiology. In the last years, the generation of genetic mouse
      models has been revolutionized by the emergence of transcription activator-like
      effector nucleases (TALENs). TALENs are programmable, sequence-specific DNA
      binding proteins fused to a non-specific endonuclease domain used as powerful
      tools for site-specific induction of DNA double-strand breaks. These result in
      disruption of the gene product of the targeted locus by mutations induced during
      repair by error-prone non-homologous end-joining. Alternatively, these DNA double
      strand breaks can be exploited to integrate a user-defined sequence by homologous
      recombination if an appropriate repair plasmid is provided. In this review, we
      highlight the major technological improvements for genome editing in murine
      oocytes which have been achieved using TALENs, discuss current limitations of the
      technology, suggest strategies to broadly apply TALENs, and describe possible
      future directions to facilitate gene editing in murine oocytes. 

PMID- 25596830
TI  - Efficacy of targeted treatment beyond third-line therapy in metastatic kidney
      cancer: retrospective analysis from a large-volume cancer center.
AB  - INTRODUCTION/BACKGROUND: Currently, 7 agents are approved for the first- and
      second-line therapy for metastatic renal cell carcinoma. In contrast, data
      supporting their use beyond second line are limited. Here we summarize our
      experience in patients treated with more than 4 lines of therapy. METHODS: We
      retrospectively assessed the outcome of 24 patients treated at our institution
      with at least 4 lines of therapy. Progression-free survival (PFS) and overall
      survival (OS) were calculated using Kaplan-Meier estimates. RESULTS: Median OS
      from the initiation of first-line therapy for the whole cohort is 64.7 months. Up
      to 96% of the patients received a tyrosine kinase inhibitor (TKI) and mammalian
      target of rapamycin (mTOR) inhibitor (mTOR-I) within the first 3 lines of
      treatment. In the fourth or following lines, patients were treated with TKI, mTOR
      I, bevacizumab/interferon, or experimental drugs. Seven patients continued
      treatment with a sixth-line agent; one has been treated up to the ninth line.
      Sixteen percent of the patients receiving fourth-line therapy and 13% receiving
      fifth-line therapy experienced a partial remission, which was independent from
      response to previous therapies. Median OS from fourth and fifth line was 30.8 and
      26.2 months, respectively. Median PFS for fourth-line therapy was 5.8 months. No
      significant difference in PFS was observed for patients with disease that
      responded or did not respond to first-line therapy. CONCLUSION: Despite the
      limitations of a retrospective analysis, our study suggests that selected
      patients benefit from multiple lines of treatment, independent of response to
      first-line therapy. However, the optimal sequence of treatment with regard to
      later lines remains to be determined.

PMID- 25596829
TI  - Human artificial chromosomes for Duchenne muscular dystrophy and beyond:
      challenges and hopes.
AB  - Safe and efficacious vectors able to carry large or several transgenes are of key
      importance for gene therapy. Human artificial chromosomes can fulfil this
      essential requirement; moreover, they do not integrate into the host genome.
      However, drawbacks such as the low efficiency of chromosome transfer and their
      relatively complex engineering still limit their widespread use. In this article,
      I summarise the key steps that brought human artificial chromosomes into
      preclinical research for Duchenne muscular dystrophy, an X-linked, monogenic
      disorder. I will also review possible future pre-clinical and clinical
      perspectives for this technology. 

PMID- 25596831
TI  - Effects of Valsalva manoeuvres and the 'CO2-off' effect on cerebral blood flow.
AB  - INTRODUCTION: Previous research has shown that a rapid drop in inhaled carbon
      dioxide (CO2) partial pressure reduces cerebral blood flow and may induce
      faintness - the 'CO2-off' effect. The aims of this study were to investigate the
      effects of performing Valsalva manoeuvres while experiencing the 'CO2-off' effect
      and whether symptoms occur that are sufficient to jeopardise submarine tower
      escape. METHODS: Twenty male volunteers, mean (SD) age 34.7 (8.5) years each
      completed three tests. The first test was to perform Valsalva manoeuvres
      breathing air. The second and third tests involved breathing a high CO2 mix (5%
      CO2/16% O(2)/79% N2) for 1 h prior to switching to breathe O2 and performing
      Valsalva manoeuvres, or switching to breathe air for 1 min then O2 and performing
      Valsalva manoeuvres. Blood pressure, cerebral blood flow velocity,
      electrocardiogram, and respiration were monitored throughout. A subjective
      questionnaire was administered at intervals to monitor symptom type and severity.
      RESULTS: Valsalva manoeuvres breathing air resulted in a 31% reduction in
      cerebral blood flow. Breathing high CO2 caused a sustained increase in cerebral
      blood flow and symptoms of breathlessness and headache. Following the gas switch
      from high CO2, some subjects reported faintness, headache and nausea. Cerebral
      blood flow dropped by 34% when switching from breathing high CO2 to O2, by 35%
      when switching to air then by a further 3% when switching from air to O2. In both
      circumstances there was a further drop of 14% after performing the Valsalva
      manoeuvres. The drop in cerebral blood flow in subjects that reported faintness
      was greater than that in the subjects who did not, but this difference was not
      significant. CONCLUSION: Transient faintness or headache may occur in the escape
      tower during pressurisation, but this should be shortlived and not
      incapacitating.

PMID- 25596832
TI  - Decompression management by 43 models of dive computer: single square-wave
      exposures to between 15 and 50 metres' depth.
AB  - INTRODUCTION: Dive computers are used in some occupational diving sectors to
      manage decompression but there is little independent assessment of their
      performance. A significant proportion of occupational diving operations employ
      single square-wave pressure exposures in support of their work. METHODS: Single
      examples of 43 models of dive computer were compressed to five simulated depths
      between 15 and 50 metres' sea water (msw) and maintained at those depths until
      they had registered over 30 minutes of decompression. At each depth, and for each
      model, downloaded data were used to collate the times at which the unit was still
      registering "no decompression" and the times at which various levels of
      decompression were indicated or exceeded. Each depth profile was replicated three
      times for most models. RESULTS: Decompression isopleths for no-stop dives
      indicated that computers tended to be more conservative than standard
      decompression tables at depths shallower than 30 msw but less conservative
      between 30-50 msw. For dives requiring decompression, computers were
      predominantly more conservative than tables across the whole depth range tested.
      There was considerable variation between models in the times permitted at all of
      the depth/decompression combinations. CONCLUSIONS: The present study would
      support the use of some dive computers for controlling single, square-wave diving
      by some occupational sectors. The choice of which makes and models to use would
      have to consider their specific dive management characteristics which may
      additionally be affected by the intended operational depth and whether staged
      decompression was permitted.

PMID- 25596833
TI  - 12-lead Holter monitoring in diving and water sports: a preliminary
      investigation.
AB  - OBJECTIVE: To demonstrate the utility of 12-lead Holter monitoring underwater.
      METHODS: A Holter monitor, recording a 12-lead electrocardiogram (ECG)
      underwater, was applied to 16 pre-trained volunteer scuba divers (13 males and
      three females). Dive computers were synchronized with the Holter recorder to
      correlate the ECG tracings with diving events. Our main objective was to
      demonstrate the utility of recording over a period of time a good quality 12-lead
      ECG underwater. The ECGs were analyzed for heart rate (HR), arrhythmias,
      conduction abnormalities and ischaemic events in relation to various stages of
      diving as follows: baseline, pre diving, diving, and post diving. RESULTS: The
      ECG tracings were of good quality with minimal artefacts. Analysis of variance
      (ANOVA) demonstrated a significant difference in HR during the various diving
      stages (P < 0.0001). Other recorded ECG abnormalities included supraventricular
      ectopic beats (four cases), ventricular ectopic beats (eight cases) and
      ventricular couplets (two cases). Conduction abnormalities included rate
      dependent right and left bundle branch block; however, these findings were
      previously known in these divers. No evidence of ischaemia was seen. CONCLUSION:
      Continuous 12-lead Holter monitoring underwater can produce good quality
      tracings. Further studies are necessary to assess its usefulness in divers at
      risk for or with known coronary artery disease, and its comparison with other
      forms of cardiac stress tests.

PMID- 25596828
TI  - De novo formed satellite DNA-based mammalian artificial chromosomes and their
      possible applications.
AB  - Mammalian artificial chromosomes (MACs) are non-integrating, autonomously
      replicating natural chromosome-based vectors that may carry a vast amount of
      genetic material, which in turn enable potentially prolonged, safe, and regulated
      therapeutic transgene expression and render MACs as attractive genetic vectors
      for "gene replacement" or for controlling differentiation pathways in target
      cells. Satellite-DNA-based artificial chromosomes (SATACs) can be made by induced
      de novo chromosome formation in cells of different mammalian and plant species.
      These artificially generated accessory chromosomes are composed of predictable
      DNA sequences, and they contain defined genetic information. SATACs have already
      passed a number of obstacles crucial to their further development as gene therapy
      vectors, including large-scale purification, transfer of purified artificial
      chromosomes into different cells and embryos, generation of transgenic animals
      and germline transmission with purified SATACs, and the tissue-specific
      expression of a therapeutic gene from an artificial chromosome in the milk of
      transgenic animals. SATACs could be used in cell therapy protocols. For these
      methods, the most versatile target cell would be one that was pluripotent and
      self-renewing to address multiple disease target cell types, thus making
      multilineage stem cells, such as adult derived early progenitor cells and
      embryonic stem cells, as attractive universal host cells. 

PMID- 25596834
TI  - The assessment and management of inner ear barotrauma in divers and
      recommendations for returning to diving.
AB  - Inner ear barotrauma (IEBt) constitutes a spectrum of pressure-related pathology
      in the inner ear, with antecedent middle ear barotrauma (MEBt) common. IEBt
      includes perilymph fistula, intralabyrinthine membrane tear, inner ear
      haemorrhage and other rarer pathologies. Following a literature search, the
      pathophysiology, diagnosis, and treatment of IEBt in divers and best-practice
      recommendations for returning to diving were reviewed. Sixty-nine papers/texts
      were identified and 54 accessed. Twenty-five case series (majority surgical)
      provided guidance on diagnostic pathways; nine solely reported divers. IEBt in
      divers may be difficult to distinguish from inner ear decompression sickness
      (IEDCS), and requires dive-risk stratification and careful interrogation
      regarding diving-related ear events, clinical assessment, pure tone audiometry, a
      fistula test and electronystagmography (ENG). Once diagnosed, conservative
      management is the recommended first line therapy for IEBt. Recompression does not
      appear to cause harm if the diagnosis (IEBt vs IEDCS) is doubtful (limited case
      data). Exploratory surgery is indicated for severe or persisting vestibular
      symptoms or hearing loss, deterioration of symptoms, or lack of improvement over
      10 days indicating significant pathology. Steroids are used, but without high
      level evidence. It may be possible for divers to return to subaquatic activity
      after stakeholder risk acceptance and informed consent, provided: (1)
      sensorineural hearing loss is stable and not severe; (2) there is no vestibular
      involvement (via ENG); (3) high-resolution computed tomography has excluded
      anatomical predilection to IEBt and (4) education on equalising techniques is
      provided. There is a need for a prospective data registry and controlled trials
      to better evaluate diagnostic and treatment algorithms. 

PMID- 25596835
TI  - Medical devices and procedures in the hyperbaric chamber.
AB  - The aim of this paper is to present current controversies concerning the safety
      of medical devices and procedures under pressure in a hyperbaric chamber
      including: defibrillation in a multiplace chamber; implantable devices during
      hyperbaric oxygen treatment (HBOT) and the results of a recent European
      questionnaire on medical devices used inside hyperbaric chambers. Early
      electrical defibrillation is the only effective therapy for cardiac arrest caused
      by ventricular fibrillation or pulseless ventricular tachycardia. The procedure
      of defibrillation under hyperbaric conditions is inherently dangerous owing to
      the risk of fire, but it can be conducted safely if certain precautions are
      taken. Recently, new defibrillators have been introduced for hyperbaric medicine,
      which makes the procedure easier technically, but it must be noted that sparks
      and fire have been observed during defibrillation, even under normobaric
      conditions. Therefore, delivery of defibrillation shock in a hyperbaric
      environment must still be perceived as a hazardous procedure. Implantable devices
      are being seen with increasing frequency in patients referred for HBOT. These
      devices create a risk of malfunction when exposed to hyperbaric conditions. Some
      manufacturers support patients and medical practitioners with information on how
      their devices behave under increased pressure, but in some cases an individual
      risk-benefit analysis should be conducted on the patient and the specific
      implanted device, taking into consideration the patient's clinical condition, the
      indication for HBOT and the capability of the HBOT facility for monitoring and
      intervention in the chamber. The results of the recent survey on use of medical
      devices inside European hyperbaric chambers are also presented. A wide range of
      non-CE-certified equipment is used in European chambers. 

PMID- 25596836
TI  - Unestablished indications for hyperbaric oxygen therapy.
AB  - Unestablished indications are conditions in which systematic clinical use of
      hyperbaric oxygen treatment (HBOT) is not supported by adequate proof of benefit.
      HBOT is vulnerable to use in many such conditions for various reasons, perhaps
      the most important being that a placebo or participation effect may create an
      impression of efficacy. The systematic use of HBOT in unestablished indications
      raises ethical concerns about provision of misleading information, giving false
      hope, and taking payment for therapy of doubtful benefit. Any practice perceived
      as unethical or unscientific has the potential to draw the wider field into
      disrepute. Of substantial contemporary relevance is the use of HBOT in treatment
      of various forms of chronic brain injury; in particular, cerebral palsy in
      children and the sequelae of mild traumatic brain injury in adults. There are now
      multiple, randomised, blinded, sham-controlled trials of HBOT in both
      indications. None of these studies showed benefit of HBOT when compared to sham
      control, though the sham and HBOT groups often both improved, indicating that a
      placebo or participation effect influenced outcomes. These results almost
      certainly explain those of open-label trials (lacking sham controls) in which
      HBOT frequently seems beneficial. Advocates for HBOT in chronic brain injury
      claim that the sham treatments (usually 1.3 ATA pressure exposure whilst air
      breathing) in the blinded trials are actually active treatments; however, the
      same dose of oxygen can be achieved at 1 ATA breathing 27% oxygen. To counter
      this argument, advocates also claim that the extra 0.3 ATA of pressure is somehow
      independently beneficial, but this notion has limited biological plausibility and
      there is little supporting evidence. Chronic brain injuries remain unestablished
      indications at this time and, in our opinion, should not be systematically
      treated with HBOT. 

PMID- 25596837
TI  - Hyperbaric medicine and the placebo effect.
AB  - The placebo in medicine has a long and interesting history. Despite the
      widespread use of placebo medication and sham interventions in clinical research,
      surprisingly little is known about how placebos work. There is evidence the
      administration of placebo preparations can induce measurable changes in
      physiology including the production of endorphins. Placebos usually involve some
      form of deception, but have been shown to work even when their lack of 'active'
      ingredients is declared to the patient. The relevance of the nature of placebo
      effects has become a central debate in the field of hyperbaric medicine with the
      recent suggestion that 131 kPa of air may be an active therapeutic intervention
      rather than a convenient and convincing sham. This paper discusses the nature of
      placebo and participation effects and the implications for hyperbaric oxygen
      therapy if low-pressure air is regarded as therapeutic. 

PMID- 25596838
TI  - Blood lead levels in scuba divers: a pilot study.
AB  - INTRODUCTION: Lead is a toxic element which is known to accumulate in the body.
      Nevertheless, it is very widely used as a diving weight. METHODS: Blood samples
      were taken from 20 recreational scuba divers to assess blood lead concentrations.
      RESULTS: The last dive before blood sampling was an average of 4.8 weeks
      previously (range 1-18 weeks). All the samples were within the normal background
      range, the highest lead concentration being 44.8 ug?L-1 with an average
      concentration of 26.5 ug?L-1 (range 11.7-44.8 ug?L-1). CONCLUSIONS: The results
      show no elevated blood lead concentrations in this group of divers compared to
      background levels. However, owing to the small number of divers studied and the
      variable, often long interval between the last dive and blood sampling, the
      results cannot be generalized.

PMID- 25596839
TI  - Severe lower limb crush injury and the role of hyperbaric oxygen treatment: a
      case report.
AB  - Open fractures with severe soft-tissue injury and critical local ischaemia of the
      lower limbs are usually difficult to treat and require a multidisciplinary
      approach. A 33-year-old Caucasian female with crush injury of the right foot
      (Gustillo IIIC) was admitted to hospital after a car accident. Despite surgical
      interventions, a persistent state of hypoxia was present because of the severe
      vessel injury, and amputation was suggested. Seventy-two hours after admission
      she was referred to the hyperbaric medicine unit for hyperbaric oxygen treatment
      (HBOT) to define the limits of viable tissues prior to amputation. After six
      sessions, clinical improvement was so obvious that the decision to amputate was
      rejected and she underwent a total of 32 HBOT in addition to frequent debridement
      and administration of antibiotics. After the HBOT course, she underwent
      successful surgical reconstruction with a vascularised cutaneous flap. Full
      healing was achieved. Given the fact that hyperbaric oxygen mechanisms of action
      target the pathophysiology of crush injuries it should be considered not only for
      the definition of viable tissue limits but also to enhance viability, even in the
      most serious situations. HBOT may prove a valuable supplement in the therapeutic
      armamentarium of these patients. 

PMID- 25596840
TI  - Australia's model work health and safety regulations and medical fitness
      requirements for professional divers.

PMID- 25596841
TI  - Insusceptibility of oxygen-evolving complex to high light in Betula platyphylla.
AB  - High mountain plants growing at high altitude have to regularly cope with high
      light and high UV radiation that can lead to photodamage of oxygen-evolving
      complex (OEC). However, the underlying mechanism of photoprotection for OEC in
      high mountain plants is unclear. Sun leaves of Betula platyphylla were used to
      examine whether cyclic electron flow (CEF) around photosystem I (PSI) plays an
      important role in photoprotection for OEC. Our results indicated that the value
      of ETRI/ETRII ratio significantly increased under high light. With increasing
      light intensity, non-photochemical quenching (NPQ) gradually increased, and the
      fraction of P700 that is oxidized in a given state gradually increased. These
      results indicated that CEF was significantly activated under high light. After
      treatment with a high light of 1600 MUmol photons m(-2) s(-1) for 8 h, the OEC
      activity did not decline, but the maximum quantum yield of PSII (F v /F m ) ratio
      significantly decreased. These results suggested that CEF-dependent generation of
      proton gradient across thylakoid membrane protected OEC activity against high
      light. Furthermore, the stability of PSI activity during exposure to high light
      suggested that the high CEF activity in B. platyphylla played an important role
      in photoprotection for PSI activity.

PMID- 25596842
TI  - Angiotensin-converting enzyme gene insertion-deletion polymorphism is a risk
      marker for Alzheimer's disease in a Chinese population: a meta-analysis of case
      control studies.
AB  - It has long been known that the polymorphisms of angiotensin-converting enzyme
      gene (ACE) are associated to increase risk of Alzheimer's disease (AD) in Chinese
      population. However, consistent results were not obtained among studies. This
      study is aimed to clarify the association between ACE insertion (I)/deletion (D)
      polymorphism (rs1799752) and AD. Literatures were searched from PubMed, Embase,
      Cochrane Library, CNKI, Wanfang and VIP databases without language restrictions.
      Eleven separate studies were suitable for the inclusion criterion. The selected
      studies contained 2,763 Chinese participants, including 1,383 in AD group and
      1,380 controls. Pooled odds ratios (ORs) were calculated to assess the
      association between ACE I/D polymorphism and AD. Our case-control data indicated
      that ACE insertion is a risk allele in all genetic models: additive model (I vs.
      D: OR = 1.32, 95 % CI 1.07-1.62, P = 0.008), dominant model (II + ID vs. DD: OR =
      1.61, 95 % CI 1.08-2.41, P = 0.02) and recessive model (II vs. ID + DD: OR =
      1.39, 95 % CI 1.07-1.81, P = 0.01). Heterogeneity between studies was significant
      (P < 0.10) but not in stratification defined by the selection of controls (P >
      0.10). After stratification according to the selection of controls, the carrier
      of ACE I allele remained a high risk for AD in population-based samples subgroup
      (I vs. D: P = 0.008, OR = 1.32, 95 % CI 1.07-1.61, P(heterogeneity) = 0.47, I (2)
      = 0 %). Our study provided solid evidence suggesting that ACE gene I/D
      polymorphism is a genetic risk factor for AD in Chinese population.

PMID- 25596844
TI  - Paenibacillus wulumuqiensis sp. nov. and Paenibacillus dauci sp. nov., two novel
      species of the genus Paenibacillus.
AB  - Two Gram-staining-positive, aerobic, motile, endospore-forming, rod-shaped
      bacteria, designated strains Y24(T) and H9(T) were isolated from cold spring and
      carrot (Daucus L.) samples, respectively, in Xinjiang Uyghur Autonomous Region,
      north-western China. The taxonomic positions of the two new isolates were
      determined by using a polyphasic approach. Phylogenetic analysis based on 16S
      rRNA gene sequences and DNA-DNA hybridizations showed that strains Y24(T) and
      H9(T) were two different novel species belonging to the genus Paenibacillus, with
      Paenibacillus hunanensis FeL05(T) as their closest relative. The genomic DNA G +
      C contents of the two isolates Y24(T) and H9(T) were 48.1 and 46.6 mol %,
      respectively. The cell wall peptidoglycan contained meso-diaminopimelic acid. The
      predominant menaquinone was both as MK-7. The major cellular fatty acids were
      anteiso-C15:0, C16:0, iso-C16:0, anteiso-C17:0 and iso-C15:0. The polar lipid
      profiles consisted of phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and two glycolipids as the major components. On the
      basis of their phenotypic characteristics, the two isolates represent two
      different novel species of the genus Paenibacillus, for which the names
      Paenibacillus wulumuqiensis sp. nov. (type strain Y24(T) = CPCC 100602(T) = JCM
      30284(T)) and Paenibacillus dauci sp. nov. (type strain H9(T) = CPCC 100608(T) =
      JCM 30283(T)) are proposed. 

PMID- 25596843
TI  - Changes in the expression of genes related to neuroinflammation over the course
      of sporadic Alzheimer's disease progression: CX3CL1, TREM2, and PPARgamma.
AB  - The role of neuroinflammation in the pathogenesis of neurodegenerative diseases
      has become more evident in recent years. Research on the etiology and
      pathogenesis of sporadic Alzheimer's disease (AD) has focused on the role of
      chemokines such as CX3CL1, on the triggering receptors expressed by myeloid cells
      (TREMs), especially TREM2, and on the transcription factor/nuclear hormone
      receptor peroxisome proliferator-activated receptor gamma (PPARgamma). Here we
      analyzed the expression levels of CX3CL1, TREM2, and PPARgamma in tissue
      homogenates from human brain regions that have different degrees of vulnerability
      to neuropathological AD-related changes to obtain insights into the pathogenesis
      and progression of AD. We found that CX3CL1 and TREM2, two genes related to
      neuroinflammation, are more highly expressed in brain regions with pronounced
      vulnerability to AD-related changes, such as the hippocampus, and that the
      expression levels reflect the course of the disease, whereas regions with low
      vulnerability to AD, seemed generally less affected by neuroinflammation.
      Furthermore, our results support previous findings of significantly higher CX3CL1
      plasma levels in patients with mild to moderate AD than in patients with severe
      AD. Thus, CX3CL1 should be considered as promising additional marker for the
      early diagnosis of AD and underlines once more, the involvement of the
      neuroinflammation in the pathogenesis of this neurodegenerative disease. 

PMID- 25596845
TI  - Balanitis is a risk factor for herpes zoster.
AB  - Both balanitis and herpes zoster (HZ) may be influenced by the immune system. The
      objective of this study was to investigate the association between balanitis and
      HZ. We selected patients aged 20 years and older who were newly diagnosed with
      balanitis from 2000 to 2010 through the Longitudinal Health Insurance Database
      2000. The non-balanitis cohort consisted of randomly selected patients who were
      matched to the balanitis cohort by age. Distributions of age and comorbidities
      were compared between the balanitis and non-balanitis cohorts; the categorical
      variables were examined using a Chi-squared test and the continuous variables
      were examined using a t-test. Univariable and multivariable Cox proportional
      hazards regression models were used to estimate the hazard ratios and 95 %
      confidence intervals for HZ among the balanitis patients in relation to the non
      balanitis patients. We identified 4,028 patients with balanitis who were matched
      based on age with 16,112 patients without balanitis. By the end of the 12-year
      follow-up, the patients with balanitis had a significantly higher cumulative
      incidence of HZ than the non-balanitis patients. The risk of HZ for patients
      without comorbidities was 1.54-fold higher in the balanitis cohort than in the
      non-balanitis cohort. The higher risk of HZ occurred during the first 6 years of
      follow-up after a diagnosis of balanitis. Balanitis is a risk factor for HZ. Men
      with balanitis have a higher risk of developing HZ. HZ vaccination might be
      necessary for men with balanitis. 

PMID- 25596846
TI  - Establishment of the forward genetic analysis of the chlorophyll d-dominated
      cyanobacterium Acaryochloris marina MBIC 11017 by applying in vivo transposon
      mutagenesis system.
AB  - Acaryochloris marina MBIC 11017 possesses chlorophyll (Chl) d as a major Chl,
      which enables this organism to utilize far-red light for photosynthesis. Thus,
      the adaptation mechanism of far-red light utilization, including Chl d
      biosynthesis, has received much attention, though a limited number of reports on
      this subject have been published. To identify genes responsible for Chl d
      biosynthesis and adaptation to far-red light, molecular genetic analysis of A.
      marina was required. We developed a transformation system for A. marina and
      introduced expression vectors into A. marina. In this study, the high-frequency
      in vivo transposon mutagenesis system recently established by us was applied to
      A. marina. As a result, we obtained mutants with the transposon in their genomic
      DNA at various positions. By screening transposon-tagged mutants, we isolated a
      mutant (Y1 mutant) that formed a yellow colony on agar medium. In the Y1 mutant,
      the transposon was inserted into the gene encoding molybdenum cofactor
      biosynthesis protein A (MoaA). The Y1 mutant was functionally complemented by
      introducing the moaA gene or increasing the ammonium ion in the medium. These
      results indicate that the mutation of the moaA gene reduced nitrate reductase
      activity, which requires molybdenum cofactor, in the Y1 mutant. This is the first
      successful forward genetic analysis of A. marina, which will lead to the
      identification of genes responsible for adaptation to far-red light. 

PMID- 25596848
TI  - Effect of workplace- versus home-based physical exercise on musculoskeletal pain
      among healthcare workers: a cluster randomized controlled trial.
AB  - OBJECTIVE: Numerous studies has shown that regular physical exercise can reduce
      musculoskeletal pain, but the optimal setting to achieve high adherence and
      effectiveness remains unknown. This study investigated the effect of workplace
      versus home-based physical exercise on musculoskeletal pain among healthcare
      workers. METHODS: The randomized controlled trial (RCT) comprised 200 female
      healthcare workers from 18 departments at 3 hospitals. Participants were randomly
      allocated at the cluster level to ten weeks of: (i) workplace physical exercise
      (WORK) performed during working hours for 5*10 minutes per week and up to 5 group
      based coaching sessions on motivation for regular physical exercise, or (ii) home
      based physical exercise (HOME) performed during leisure time for 5*10 minutes per
      week. Both groups received ergonomic counseling on patient handling and use of
      lifting aides. Average pain intensity (0-10 scale) in the low back and
      neck/shoulder was the primary outcome. RESULTS: Per week, 2.2 (SD 1.1) and 1.0
      (SD 1.2) training sessions were performed in WORK and HOME groups, respectively.
      Pain intensity, back muscle strength and use of analgesics improved more
      following WORK than HOME (P<0.05). Between-group differences at follow-up (WORK
      versus HOME) was -0.7 points for pain intensity [95% confidence interval (95% CI)
      -1.0- -0.3], 5.5 Nm for back muscle strength (95% CI 2.0-9.0), and -0.4 days per
      week for use of analgesics (95% CI -0.7- -0.2). The effect size for between-group
      differences in pain intensity was small (Cohen's d=0.31). CONCLUSIONS: Workplace
      physical exercise is more effective than home-based exercise in reducing
      musculoskeletal pain, increasing muscle strength and reducing the use of
      analgesics among healthcare workers.

PMID- 25596847
TI  - Energy transfer in Anabaena variabilis filaments under nitrogen depletion,
      studied by time-resolved fluorescence.
AB  - Some filamentous cyanobacteria (including Anabaena) differentiate into
      heterocysts under nitrogen-depleted conditions. During differentiation, the
      phycobiliproteins and photosystem II in the heterocysts are gradually degraded.
      Nitrogen depletion induces changes in the pigment composition of both vegetative
      cells and heterocysts, which affect the excitation energy transfer processes. To
      investigate the changes in excitation energy transfer processes of Anabaena
      variabilis filaments grown in standard medium (BG11) and a nitrogen-free medium
      (BG110), we measured their steady-state absorption spectra, steady-state
      fluorescence spectra, and time-resolved fluorescence spectra (TRFS) at 77 K. TRFS
      were measured with a picosecond time-correlated single photon counting system.
      The pigment compositions of the filaments grown in BG110 changed throughout the
      growth period; the relative phycocyanin levels monotonically decreased, whereas
      the relative carotenoid (Car) levels decreased and then recovered to their
      initial value (at day 0), with formation of lower-energy Cars. Nitrogen
      starvation also altered the fluorescence kinetics of PSI; the fluorescence
      maximum of TRFS immediately after excitation occurred at 735, 740, and 730 nm
      after 4, 8, and 15 days growth in BG110, respectively. Based on these results, we
      discuss the excitation energy transfer dynamics of A. variabilis filaments under
      the nitrogen-depleted condition throughout the growth period. 

PMID- 25596849
TI  - Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response
      in BALB/c mice and in primary intestinal epithelial cell culture involving toll
      like receptors TLR-2 and TLR-4.
AB  - PURPOSE: Active Hexose Correlated Compound (AHCC((r))) is a cultured mushroom
      extract that is commercially available and promoted for immune support. Available
      data suggest that AHCC supplementation affects immune cell populations and immune
      outcomes, including natural killer cell response to infection. The mechanism by
      which AHCC exerts its effects is not well understood. The present work aimed to
      characterize the immunomodulatory activity of AHCC in the gut and to study the
      effects of AHCC on toll-like receptor (TLR) signaling in intestinal epithelial
      cells (IECs). METHODS: BALB/c mice were fed AHCC by gavage. In vivo activities
      were assessed by immunohistochemistry and cytokine production. The effects of
      AHCC on ex vivo primary cell culture from IECs were examined after challenge with
      LPS or E. coli alone or in the presence of anti-TLR-2 and TLR-4 blocking
      antibodies. RESULTS: Feeding AHCC resulted in increased IgA+ cells in the
      intestine and increased sIgA, IL-10, and IFN-gamma in the intestinal fluid. In
      IECs, contact with AHCC increased IL-6 production but not to the pro-inflammatory
      level of positive controls, LPS and E. coli. Blocking TLR-2 and TLR-4 reduced the
      induction of IL-6 by AHCC, suggesting that these innate receptors are involved in
      generating the immune response of IECs to AHCC. CONCLUSIONS: AHCC may play a role
      in the orchestration of immune response and the maintenance of immune homeostasis
      in part by priming the TLR-2 and TLR-4 gate at the intestinal epithelium. Such a
      response is likely due to the recognition of non-pathogenic food-associated
      molecular patterns (FAMPs) such as those found associated with other mushroom or
      yeast-derived compounds.

PMID- 25596851
TI  - Speaking from the Inside: Challenges Faced by Communication Researchers
      Investigating Disease-Related Issues in a Hospital Setting.
AB  - This commentary came from within the framework of integrating the humanities in
      medicine and from accompanying research on disease-related issues by teams
      involving clinicians and researchers in medical humanities. The purpose is to
      reflect on the challenges faced by researchers when conducting emotionally laden
      research and on how they impact observations and subsequent research findings.
      This commentary is furthermore a call to action since it promotes the
      institutionalization of a supportive context for medical humanities researchers
      who have not been trained to cope with sensitive medical topics in research. To
      that end, concrete recommendations regarding training and supervision were
      formulated. 

PMID- 25596850
TI  - CVD-predictive performances of "a body shape index" versus simple anthropometric
      measures: Tehran lipid and glucose study.
AB  - PURPOSE: To examine whether a body shape index (ABSI) calculated by using waist
      circumference (WC) adjusted for height and weight could improve the predictive
      performances for cardiovascular disease (CVD) of the Framingham's general CVD
      algorithm and to compare its predictive performances with other anthropometric
      measures. METHODS: We analyzed data on a 10-year population-based follow-up of
      8,248 (4,471 women) individuals aged >=30 years, free of CVD at baseline. CVD
      risk was estimated for a 1 SD increment in ABSI, body mass index (BMI), waist-to
      hip ratio (WHpR) and waist-to-height ratio (WHtR), by incorporating them, one at
      a time, into multivariate accelerated failure time models. RESULTS: ABSI was
      associated with multivariate-adjusted increased risk of incident CVD among both
      men (1.26, 95% CI 1.09-1.46) and women (1.17, 1.03-1.32). Among men, for a one-SD
      increment, ABSI conferred a greater increase in the hazard of CVD [1.26 (1.09
      1.46)] than did BMI [1.06 (0.94-1.20)], WC [1.15(1.03-1.28)], WHpR [1.02 (1.01
      1.03)] and WHtR [1.16 (1.02-1.31)], and the corresponding figures among women
      were 1.17 (1.03-1.32), 1.02 (0.90-1.16), 1.11 (0.98-1.27), 1.03 (1.01-1.05) and
      1.14 (0.99-1.03), respectively. ABSI as well as other anthropometric measures
      failed to add to the predictive ability of the Framingham general CVD algorithm
      either. CONCLUSIONS: Although ABSI could not improve the predictability of the
      Framingham algorithm, it provides more information than other traditional
      anthropometric measures in settings where information on traditional CVD risk
      factors are not available, and it can be used as a practical criterion to predict
      adiposity-related health risks in clinical assessments.

PMID- 25596852
TI  - Association of nicotinamide-N-methyltransferase mRNA expression in human adipose
      tissue and the plasma concentration of its product, 1-methylnicotinamide, with
      insulin resistance.
AB  - AIMS/HYPOTHESIS: Nicotinamide-N-methyltransferase (NNMT) was recently shown to be
      upregulated in mouse models of insulin resistance and obesity. So far, it is
      unknown whether NNMT is regulated in human disease. We have explored the
      hypothesis that white adipose tissue (WAT) NNMT expression and plasma 1
      methylnicotinamide (MNA) concentration are increased in human insulin resistance
      and type 2 diabetes. METHODS: NNMT expression and plasma MNA were analysed in
      three groups of individuals: (1) 199 patients undergoing abdominal surgery; (2)
      60 individuals on a 12-week exercise programme and (3) 55 patients on a two-step
      bariatric surgery programme. RESULTS: Patients with manifest type 2 diabetes have
      a significantly (approximately twofold) higher NNMT expression both in omental
      and subcutaneous WAT compared with controls. Notably, plasma MNA correlated
      significantly with WAT NNMT expression in patients with type 2 diabetes (women, r
      = 0.59, p < 0.001; men, r = 0.61, p < 0.001) but not in healthy control
      individuals. In insulin-resistant individuals, there was an inverse correlation
      between insulin sensitivity and plasma MNA (r = 0.44, p = 0.01) or adipose tissue
      NNMT mRNA (r = 0.64, p < 0.001). The latter association was confirmed in a second
      cohort (n = 60, r = 0.78, p < 0.001). Interventions improving insulin sensitivity
      -exercise and bariatric surgery--were associated with a significant (p < 0.001)
      reduction in WAT NNMT expression. Bariatric surgery was also associated with a
      significant decrease in plasma MNA. CONCLUSIONS/INTERPRETATION: We demonstrate
      that WAT NNMT expression is regulated in human insulin resistance and type 2
      diabetes and that plasma MNA correlates with increased tissue NNMT expression and
      the degree of insulin resistance, making it a potential biomarker for loss of
      insulin sensitivity.

PMID- 25596853
TI  - History of infertility and risk of type 2 diabetes mellitus: a prospective cohort
      study.
AB  - AIMS/HYPOTHESIS: We sought to evaluate the relationship between delayed
      conception and type 2 diabetes risk, given that there are plausible underlying
      mechanisms linking the two, including inflammation and insulin resistance.
      METHODS: Participants of the Nurses' Health Study II prospective cohort were
      included if they were free of chronic disease (cardiovascular disease, type 2
      diabetes, cancer) at baseline. Biennial questionnaires updated information on
      infertility status (>12 months attempted pregnancy), lifestyle characteristics
      and several health-related outcomes. Self-reported cases of diabetes were
      confirmed using a follow-up questionnaire. Multivariable Cox proportional hazards
      models were used to compute the HRs and 95% CIs. RESULTS: Incident type 2
      diabetes occurred in 5,993 of the 112,106 participants over 24 years of follow-up
      (1989-2013). A history of infertility was reported in 27,774 (24.8%) women and
      was associated with a 20% greater risk of developing diabetes, compared with
      those never reporting infertility (HR 1.20 [95% CI 1.14, 1.28]), after adjusting
      for age, lifestyle factors, marital status, oral contraceptive use, family
      history of diabetes and BMI. Compared with women without a history of
      infertility, the causes of infertility associated with a higher diabetes risk
      were ovulation disorders (HR 1.43 [95% CI 1.29, 1.58]) and tubal factor (HR 1.34
      [95% CI 1.13, 1.58]). Cervical factor (HR 1.06 [95% CI 0.81, 1.40]) and
      endometriosis (HR 1.06 [95% CI 0.89, 1.27]) were not associated, while male
      factor infertility was associated with a modestly higher diabetes risk (HR 1.15
      [95% CI 1.00, 1.33]). CONCLUSIONS/INTERPRETATION: These novel findings suggest a
      history of infertility, particularly that related to ovulation disorders and
      tubal blockage, is significantly associated with a higher risk of type 2
      diabetes.

PMID- 25596855
TI  - Reproductive performance, metabolic and hormonal profiles of Santa Ines ewes in
      winter and summer under tropical conditions.
AB  - The study aimed to evaluate the reproductive, metabolic and hormonal profiles of
      Santa Ines ewes during winter and summer in the tropical climate of Rio de
      Janeiro State, Brazil. The ewes (n = 16) were prepared for induction of
      synchronised oestrus with a short-term hormonal treatment, and follicular
      dynamics were assessed with ultrasonography. Blood samples for biochemical and
      hormonal analyses were collected on days zero, six and eight of the protocol at
      7, 13 and 19 h. Reproductive behaviour did not differ (P > 0.05) between seasons.
      Based on ultrasonography data, the ovulation rate was 100% in summer and 81.3% in
      winter. Most of the ewes showed double ovulation in summer, and the diameter of
      the largest and second largest follicles differed (P < 0.05) between seasons.
      Among the biochemical parameters, plasma glucose, plasma urea and serum albumin
      differed (P < 0.05) between the study periods. Regarding the hormonal profile,
      higher serum triiodothyronine, thyroxine and prolactin concentrations (P < 0.05)
      were observed in summer. The average progesterone concentrations demonstrated low
      reproductive seasonality. In conclusion, the reproductive performance of the ewes
      was superior in summer, and higher levels of plasma glucose and serum albumin
      during this season may have played a role in the observed ovulation rates. The
      higher levels of serum prolactin and serum thyroxine in summer demonstrated that
      these compounds were not involved in the regulatory mechanisms underlying the
      onset of anoestrus in these Santa Ines ewes under tropical conditions.

PMID- 25596854
TI  - Role of milk fat globule-epidermal growth factor 8 in colonic inflammation and
      carcinogenesis.
AB  - BACKGROUND: Milk fat globule-epidermal growth factor 8 (MFG-E8) promotes
      phagocytic clearance of apoptotic cells to maintain normal tissue homeostasis.
      However, its functions in intestinal inflammation and carcinogenesis are unknown.
      METHODS: Experimental colitis was induced in MFG-E8 knockout (KO) and wild-type
      (WT) mice by dextran sodium sulfate (DSS) administration. Colon tissues were used
      for assessments of colitis activity and epithelial proliferation. A mouse colitis
      associated cancer (CAC) model was induced by intraperitoneal injection of
      azoxymethane (AOM) and then the animals were given a single administration of
      DSS. A sporadic colon cancer model was established by repeated intraperitoneal
      injections of AOM. The role of MFG-E8 in epithelial proliferation with or without
      treatment of siRNA targeting alpha(v)-integrin was examined in vitro using a WST
      1 assay. RESULTS: The severity of colitis in KO mice was greater than that in WT
      mice, while the proliferative potential of colonic epithelial cells in KO mice
      was lower during the regenerative phase. In both CAC and sporadic models, tumor
      size in KO was lower as compared to WT mice, while decreased tumor incidence was
      only found in the CAC model. In vitro findings showed that MFG-E8 promotes
      epithelial cell proliferation, and treatment with a siRNA targeting alpha(v)
      integrin reduced the proliferation of Colon-26 cells stimulated with recombinant
      MFG-E8. CONCLUSIONS: MFG-E8 promotes tumor growth regardless of the presence or
      absence of colonic inflammation, whereas colon tumor development is initiated by
      MFG-E8 under inflammatory conditions. These MFG-E8 functions may be dependent on
      integrin-mediated cellular signaling.

PMID- 25596856
TI  - Molecular cloning, sequencing and phylogeny of vasotocin receptor genes in the
      air-breathing catfish Heteropneustes fossilis with sex dimorphic and seasonal
      variations in tissue expression.
AB  - Vasotocin (VT) is the ortholog of vasopressin (VP) in non-mammalian vertebrates
      and is known for multiple functions. Teleost fishes have a complete repertoire of
      known VP/VT receptor subtypes (vasopressin type, VR): two V1A subtypes (V1Aa and
      V1Ab or V1a1 and V1a2) and five V2 subtypes (V2A1, V1A2, V2B1, V2B2 and V2C).
      Full-length cDNAs of v1a1, v1a2 and v2 (v2a1) with ORFs of 1,308, 1,137 and 1,527
      bp, respectively, were cloned and characterized in the catfish Heteropneustes
      fossilis (Siluriformes, Ostariophysi). BLAST analysis revealed that the genes
      encoded three VT receptors, V1a1, V1a2 and V2 of 436, 379 and 509 amino acid
      residues, respectively. The predicted proteins showed typical features of the
      seven-transmembrane domain receptor core structure with hallmark triplets Asp-Arg
      Tyr/Asp-Arg-His (DRY/DRH) and the variable intracellular loop III of vertebrate
      neurohypophysial hormone receptors. Phylogenetic analysis of the deduced protein
      sequences revealed that they clustered with the V1Aa, V1Ab and V2A1,
      respectively, of other teleosts. The V2R has a sequence identity of 70-76% with
      V2A1 than with the V2B type (sequence identity 43-49%). Semiquantitative PCR
      analysis showed that the receptor gene transcripts were expressed ubiquitously in
      the tissues examined (brain, pituitary, gonads, liver, muscle, kidney and gills)
      and displayed sex and seasonal fluctuations in a tissue-specific manner. The
      results form a basis for functional studies on the VT receptors in the catfish.

PMID- 25596858
TI  - Cellular Immunology--mission statement.

PMID- 25596857
TI  - Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected
      youths.
AB  - Reduced bone mineral density (BMD) and altered bone metabolism are common
      findings in HIV-infected patients. Increased bone formation has been described
      both in HIV-infected adults and children. Wnt ligands promote bone formation by
      stimulating osteoblast differentiation and their survival. Sclerostin and
      dickkopf factor 1 (DKK-1), Wnt antagonists, are important negative regulators of
      bone formation. We studied 86 HIV-infected patients whose ages ranged from 5.7 to
      27.9 years. Patients were all on antiretroviral therapy, but seven who were naive
      to treatment. Bone alkaline phosphatase (BAP), sclerostin, and DKK-1 were
      measured in serum by enzyme immunoassay. BMD was measured by dual-energy X-ray
      absorptiometry at the lumbar spine and in the whole skeleton. Biochemical indexes
      were also measured in 143 healthy controls (age range 4.5-27.4 years). HIV
      infected patients had lower than normal BMD (spine P < 0.005, and whole skeleton
      P < 0.03). BAP measurements were significantly higher in HIV-infected patients
      than controls (P <= 0.05). Sclerostin and DKK-1 concentrations were markedly
      lower than in controls (P <= 0.0006, and P <= 0.03, respectively). The serum
      concentration of both analytes of patients naive to antiretroviral treatment was
      not different from that of treated patients. No correlations were found between
      sclerostin, DKK-1, and bone mineral measurements. Our data confirm the alteration
      of bone metabolism pathways in HIV-infected individuals. The lower concentration
      of Wnt antagonists is consistent with the increased bone formation markers.

PMID- 25596859
TI  - Subcutaneous mycoses: an aetiological study of 15 cases in a tertiary care
      hospital at Dibrugarh, Assam, northeast India.
AB  - Subcutaneous mycoses are a group of fungal infections of dermis and subcutaneous
      tissue which consist of sporotrichosis, chromoblastomycosis, phaeohyphomycosis,
      hyalohyphomycosis, mycetoma, subcutaneous zygomycosis, rhinosporidiosis,
      lobomycosis and disseminated penicilliosis. A total of 46 consecutive patients
      with clinically suspected subcutaneous mycoses attending various departments of
      Assam Medical College and Hospital were included in this prospective study to
      know the prevalence of subcutaneous mycoses in this eastern part of Assam. Direct
      microscopy in 10 and 40 % KOH, histopathological examination of biopsied tissue,
      colony characteristics on Sabourauds dextrose agar media both at 25 and 37 
      degrees C and detailed morphology of each fungus on lactophenol cotton blue mount
      were the basis of identification of the fungi. Subcutaneous mycoses were
      confirmed in 32.6 % (n = 15) cases. Out of 15 positive cases of subcutaneous
      mycoses, chromoblastomycosis was detected in six cases (n = 40 %),
      hyalohyphomycosis in three cases (n = 20 %), and lymphocutaneous sporotrichosis,
      disseminated penicilliosis and mycetoma in two cases each (n = 13.3 % each). In
      this study, seven different species of fungus were found to be responsible for
      five different clinical types of subcutaneous mycosis. Cladosporium
      cladosporioides, Bipolaris spicifera and Curvularia lunata were responsible for
      chromoblastomycosis, Fusarium oxysporum and Aspergillus terreus for
      hyalohyphomycosis, C. lunata for mycetoma, Sporothrix schenckii for
      lymphocutaneous sporotrichosis and Penicillium marneffei for disseminated
      penicilliosis. C. cladosporioides and C. lunata were the commonest black fungi
      causing subcutaneous mycosis in this sub-Himalayan belt. Rare species C.
      cladosporioides, B. spicifera and C. lunata were found to be causing
      chromoblastomycosis in this study.

PMID- 25596860
TI  - Design, construction and mechanical testing of digital 3D anatomical data-based
      PCL-HA bone tissue engineering scaffold.
AB  - The study aims to investigate the techniques of design and construction of CT 3D
      reconstructional data-based polycaprolactone (PCL)-hydroxyapatite (HA) scaffold.
      Femoral and lumbar spinal specimens of eight male New Zealand white rabbits were
      performed CT and laser scanning data-based 3D printing scaffold processing using
      PCL-HA powder. Each group was performed eight scaffolds. The CAD-based 3D printed
      porous cylindrical stents were 16 piece * 3 groups, including the orthogonal
      scaffold, the Pozi-hole scaffold and the triangular hole scaffold. The gross
      forms, fiber scaffold diameters and porosities of the scaffolds were measured,
      and the mechanical testing was performed towards eight pieces of the three kinds
      of cylindrical scaffolds, respectively. The loading force, deformation, maximum
      affordable pressure and deformation value were recorded. The pore-connection rate
      of each scaffold was 100 % within each group, there was no significant difference
      in the gross parameters and micro-structural parameters of each scaffold when
      compared with the design values (P > 0.05). There was no significant difference
      in the loading force, deformation and deformation value under the maximum
      affordable pressure of the three different cylinder scaffolds when the load was
      above 320 N. The combination of CT and CAD reverse technology could accomplish
      the design and manufacturing of complex bone tissue engineering scaffolds, with
      no significant difference in the impacts of the microstructures towards the
      physical properties of different porous scaffolds under large load.

PMID- 25596862
TI  - Effect of coupling asynchronous acoustoelectric effects on the corrosion
      behavior, microhardness and biocompatibility of biomedical titanium alloy strips.
AB  - The coupling asynchronous acoustoelectric effects (CAAE) of the high-energy
      electropulsing treatment (EPT) technique and ultrasonic surface strengthening
      modification (USSM) are innovatively combined in improving the surface
      microhardness, corrosion behavior and biocompatibility of the pre-deformed
      titanium alloy strips. Experimental results show that EPT and USSM processes
      facilitate the surface grain refining and USSM brings in the micro-dimples on the
      materials surface, which is attributed to the atoms diffusion acceleration under
      EPT and severe surface plastic deformation under USSM. These microstructure
      changes can not only enhance the corrosion resistance in the acidic simulated
      body fluids and fluoridated acidic artificial saliva but also improve the
      biocompatibility of the titanium alloy strip materials. Moreover, the surface
      microhardness of the titanium alloy strips is enhanced to improve the wear
      resistance. Therefore, CAAE processing is a high-efficiency and energy-saving
      method for obtaining biomedical titanium alloys with superior anti-corrosion
      performance, microhardness and biocompatibility, which can be widely applied in
      dental implants and artificial joint. 

PMID- 25596861
TI  - Dual effects of beta-cyclodextrin-stabilised silver nanoparticles: enhanced
      biofilm inhibition and reduced cytotoxicity.
AB  - The composition and mode of synthesis of nanoparticles (NPs) can affect
      interaction with bacterial and human cells differently. The present work
      describes the ability of beta-cyclodextrin (beta-CD) capped silver nanoparticles
      (AgNPs) to inhibit biofilm growth and reduce cytotoxicity. Biofilm formation of
      Staphylococcus epidermidis CSF 41498 was quantified by a crystal violet assay in
      the presence of native and capped AgNPs (Ag-10CD and Ag-20CD), and the morphology
      of the biofilm was observed by scanning electron microscope. The cytotoxicity of
      the AgNPs against HaCat cells was determined by measuring the increase in
      intracellular reactive oxygen species and change in mitochondrial membrane
      potential (DeltaPsim). Results indicated that capping AgNPs with beta-CD improved
      their efficacy against S. epidermidis CSF 41498, reduced biofilm formation and
      their cytotoxicity. The study concluded that beta-CD is an effective capping and
      stabilising agent that reduces toxicity of AgNPs against the mammalian cell while
      enhancing their antibiofilm activity.

PMID- 25596863
TI  - Silicate-substituted calcium phosphate with enhanced strut porosity stimulates
      osteogenic differentiation of human mesenchymal stem cells.
AB  - While many synthetic ceramic bone graft substitutes (BGSs) have osteoconductive
      properties (e.g. provide a physical scaffold for osteointegration of surrounding
      bone tissue), certain BGSs are osteostimulative in that they actively upregulate
      mesenchymal stem cell proliferation and stimulate differentiation into osteoblast
      like cells. The osteostimulative properties of silicate-substituted calcium
      phosphate with enhanced porosity (SiCaP EP) were evaluated in vitro with STRO-1+
      immunoselected human bone marrow derived mesenchymal stem cells (HBMSCs).
      Osteostimulative materials (SiCaP) and Bioglass 45S5 (Bioglass) were also
      assessed as positive controls along with non-silicate substituted hydroxyapatite
      as a negative control. HBMSCs were also assessed on Thermanox discs cultured in
      basal and osteogenic media to determine when osteogenic differentiation could be
      significantly detected with this in vitro cell system. HBMSC viability and
      necrosis, total DNA content, alkaline phosphatase (ALP) expression, and
      osteocalcin expression were evaluated after 7, 14, 21, and 28 days. It was
      demonstrated that SiCaP EP is osteostimulative based on its propensity to support
      STRO-1+ HBMSC proliferation and ability to promote the differentiation of HBMSCs
      down the osteoblastic lineage from ALP-expressing, matrix-producing osteoblasts
      to Osteocalcin-producing pre-osteocytes without the presence of external
      osteogenic factors. SiCaP EP permitted greater HBMSC attachment as well as ALP
      and Osteocalcin expression than Bioglass which may be attributed to its
      microstructure and chemistry.

PMID- 25596866
TI  - Environmental enrichment rescues memory in mice deficient for the
      polysialytransferase ST8SiaIV.
AB  - The neural cell adhesion molecule NCAM and its association with the polysialic
      acid (PSA) are believed to contribute to brain structural plasticity that
      underlies memory formation. Indeed, the attachment of long chains of PSA to the
      glycoprotein NCAM down-regulates its adhesive properties by altering cell-cell
      interactions. In the brain, the biosynthesis of PSA is catalyzed by two
      polysialyltransferases, which are differentially regulated during lifespan. One
      of them, ST8SiaIV (PST), is predominantly expressed during adulthood whereas the
      other one, ST8SiaII (STX), dominates during embryonic and post-natal development.
      To understand the role played by ST8SiaIV during learning and memory and its
      underlying hippocampal plasticity, we used knockout mice deleted for the enzyme
      ST8SiaIV (PST-ko mice). At adult age, PST-ko mice show a drastic reduction of PSA
      NCAM expression in the hippocampus and intact hippocampal adult neurogenesis. We
      found that these mice display impaired long-term but not short-term memory in
      both, spatial and non-spatial behavioral tasks. Remarkably, memory deficits of
      PST-ko mice were abolished by exposure to environmental enrichment that was also
      associated with an increased number of PSA-NCAM expressing new neurons in the
      dentate gyrus of these mice. Whether the presence of a larger pool of immature,
      likely plastic, new neurons favored the rescue of long-term memory in PST-ko mice
      remains to be determined. Our findings add new evidence to the role played by PSA
      in memory consolidation. They also suggest that PSA synthesized by PST critically
      controls the tempo of new neurons maturation in the adult hippocampus. 

PMID- 25596864
TI  - Low-grade intraventricular hemorrhage disrupts cerebellar white matter in preterm
      infants: evidence from diffusion tensor imaging.
AB  - INTRODUCTION: Recent diffusion tensor imaging (DTI) studies have demonstrated
      that leakage of hemosiderin into cerebrospinal fluid (CSF), which is caused by
      high-grade intraventricular hemorrhage (IVH), can affect cerebellar development
      in preterm born infants. However, a direct effect of low-grade IVH on cerebellar
      development is unknown. Thus, we evaluated the cerebellar and cerebral white
      matter (WM) of preterm infants with low-grade IVH. METHODS: Using DTI
      tractography performed at term-equivalent age, we analyzed 42 infants who were
      born less than 30 weeks gestational age (GA) at birth (22 with low-grade IVH, 20
      without). These infants were divided into two birth groups depending on GA, and
      we then compared the presence and absence of IVH which was diagnosed by cerebral
      ultrasound (CUS) within 10 days after birth or conventional magnetic resonance
      imaging (MRI) at term-equivalent age in each group. Fractional anisotropy (FA)
      and apparent diffusion coefficient (ADC) at the superior cerebellar peduncle
      (SCP), middle cerebellar peduncle (MCP), motor tract, and sensory tract were
      measured. RESULTS: In the SCP, preterm born infants with IVH had lower FA values
      compared with infants without IVH. In particular, younger preterm birth with IVH
      had lower FA values in the SCP and motor tract and higher ADC values in the MCP.
      CONCLUSION: Low-grade IVH impaired cerebellar and cerebral WM, especially in the
      SCP. Moreover, younger preterm infants exhibited greater disruptions to
      cerebellar WM and the motor tract than infants of older preterm birth.

PMID- 25596867
TI  - Burnout: absence of binding diagnostic criteria hampers prevalence estimates.

PMID- 25596865
TI  - In vivo characterization of metabotropic glutamate receptor type 5 abnormalities
      in behavioral variant FTD.
AB  - Although the pathogenesis underlying behavioral variant frontotemporal dementia
      (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been
      hypothesized to play an important role. The aim of the present study was to
      determine the availability of the metabotropic glutamate receptor type 5 (mGluR5)
      using a novel positron emission tomography (PET) radiopharmaceutical with high
      selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In
      addition, we sought to determine the overlap between availability of mGluR5 and
      neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry
      (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured
      in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688
      binding potential maps (BPND) were calculated using the cerebellum as a reference
      region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the
      pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based
      group differences were obtained using RMINC. BvFTD patients showed widespread
      decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical
      areas. These areas were likewise characterized by significant hypometabolism and
      GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism
      superior to that for GM atrophy. Several regions were characterized only by
      decreased binding of [(11)C]ABP688. The present findings represent the first in
      vivo report of decreased availability of mGluR5 in bvFTD. This study suggests
      that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and
      that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission
      in vivo.

PMID- 25596868
TI  - High-risk patients with inoperative aortic stenosis: use of transapical,
      transaortic, and transcarotid techniques.
AB  - BACKGROUND: Patient characteristics and procedural outcomes from nontransfemoral
      (non-TF) transcatheter aortic valve replacement (TAVR) in high-risk or inoperable
      patients with aortic stenosis have been incompletely reported. The purpose of
      this study was to compare outcomes with non-TF TAVR access techniques including
      transapical (TA), transaortic (TAo), and transcarotid (TC) TAVR with a balloon
      expandable valve. METHODS: A retrospective review was performed of all patients
      undergoing TA, TAo, and TC TAVR from 2007 to 2013 at Emory University.
      Preoperative risk factors and postoperative outcomes were evaluated using Valve
      Academic Research Consortium-2 definitions. RESULTS: Of 469 patients undergoing
      TAVR during that period at our institution, 139 underwent TA TAVR, 35 had Tao
      TAVR, and 11 had TC TAVR. Patients undergoing TC TAVR were younger than those
      undergoing TA TAVR and TAo TAVR (mean ages: TC, 68.9 +/- 23.6 years; TA, 81.3 +/-
      7.7 years; Tao, 83.8 +/- 8.3 years; p = 0.017). Most patients undergoing TAo TAVR
      were women (82.9%), whereas patients undergoing TA TAVR were more likely to be
      men (62.6%). Slightly more than half of patients undergoing TA TAVR (54.7%) and
      TC (54.6%) TAVR had undergone previous coronary artery bypass grafting (CABG),
      whereas no patients underwent TAo TAVR (0%). There was no preoperative difference
      in ejection fraction, New York Heart Association classification, significant
      chronic obstructive pulmonary disease, and The Society of Thoracic Surgeons
      predicted risk of mortality between TA TAVR, Tao TAVR, and TC TAVR, respectively.
      Average postoperative length of stay was 9 to 11 days and was similar among
      groups (p = 0.22). There were 13 (9.4%) TA TAVR operative deaths and 4 (11.4%)
      operative deaths in the TAo TAVR group. There were no deaths in the TC TAVR
      group. CONCLUSIONS: In high-risk and inoperable patients who are not candidates
      for TF TAVR, careful selection of alternative access options can lead to
      excellent and comparable postoperative outcomes.

PMID- 25596869
TI  - Tricuspid repair at pulmonary valve replacement does not alter outcomes in
      tetralogy of Fallot.
AB  - BACKGROUND: Chronic pulmonary regurgitation after tetralogy of Fallot repair
      often leads to progressive right ventricle dilation, dysfunction, and frequently,
      pulmonary valve replacement. For those with significant tricuspid regurgitation
      at the time of pulmonary valve replacement, it is unknown whether concomitant
      tricuspid valve repair improves postoperative outcomes. METHODS: This is a
      retrospective review of patients after tetralogy of Fallot repair who underwent
      pulmonary valve replacement between 1999 and 2012. Preoperative and postoperative
      echocardiograms were assessed for tricuspid regurgitation (vena contracta) and
      right ventricular size and function (Tomtec software). RESULTS: Sixty-two
      patients underwent pulmonary valve replacement. Thirty-six (58%) had greater than
      or equal to moderate tricuspid regurgitation on preoperative echocardiogram.
      Significant predictors were not identified. Of the 36, 18 (50%) underwent
      concomitant tricuspid valve repair at the time of pulmonary valve replacement.
      After surgery, there was a significant reduction in the degree of tricuspid
      regurgitation (p < 0.001) and measures of right ventricular size (p < 0.05) in
      both cohorts. Between surgical groups, there was no statistical difference in the
      grade of tricuspid regurgitation (p = 0.47) or measures of right ventricular size
      (p > 0.4) at 6-month follow-up. CONCLUSIONS: Tricuspid regurgitation is a common
      finding in repaired tetralogy of Fallot, although risk factors for its
      development remain unclear. After pulmonary valve replacement with or without
      tricuspid valve repair there is significant improvement in the degree of
      tricuspid regurgitation and right ventricular size. Finally, 6 months after
      pulmonary valve replacement there were no statistical differences between those
      patients undergoing concomitant tricuspid valve repair and those undergoing
      pulmonary valve replacements alone.

PMID- 25596870
TI  - Predictors of survival after operation among patients with large cell
      neuroendocrine carcinoma of the lung.
AB  - BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) represents a rare entity
      in non-small cell lung cancer, with only partially understood biology and poor
      survival. A diagnosis is difficult to obtain on the basis of small biopsy
      specimens, but surgical procedures may be indicated in only a small fraction of
      patients. The aim of this study was to assess the clinical and
      immunohistochemical features of patients with LCNEC to identify predictors of
      outcome and long-term survival. METHODS: The clinical and pathologic data of 57
      surgical patients with LCNEC between March 2003 and December 2012 were
      retrospectively reviewed. The tumor specimens were examined for expression of
      neuronal specific enolase, synaptophysin, CD 56, chromogranin-A, and the
      somatostatin receptor by immunohistochemistry. Statistical analysis was performed
      to determine significant predictors for overall survival and recurrence-free
      survival. RESULTS: Fifty-seven patients (41 men, 16 women) underwent thoracic
      operations with curative intent. Complete resection was achieved in 91% of cases.
      The results of staining for CD56, synaptophysin, neuronal specific enolase,
      chromogranin-A, and somatostatin were positive in 86%, 81%, 68%, 61%, and 21%,
      respectively. Recurrence occurred in 28 patients (49%). Overall survival and
      recurrence-free survival were 50% and 45%, respectively, after 3 years. Advanced
      nodal status (N1, p < 0.025; N2, p < 0.02) and simultaneous expression of CD56
      and chromogranin-A (p < 0.04) were significantly associated with poorer outcome.
      CONCLUSIONS: LCNEC is a rare neuroendocrine pulmonary malignancy that is
      associated with poor prognosis and high recurrence rates. Surgical treatment can
      achieve satisfactory results in selected cases. Neuroendocrine marker profiles
      may predict prognosis and may influence the decision for adjuvant therapy or
      follow-up intervals.

PMID- 25596872
TI  - Direct AFM force measurements between air bubbles in aqueous polydisperse sodium
      poly(styrene sulfonate) solutions: effect of collision speed, polyelectrolyte
      concentration and molar mass.
AB  - Interactions between colliding air bubbles in aqueous solutions of polydisperse
      sodium poly(styrene sulfonate) (NaPSS) using direct force measurements were
      studied. The forces measured with deformable interfaces were shown to be more
      sensitive to the presence of the polyelectrolytes when compared to similar
      measurements using rigid interfaces. The experimental factors that were examined
      were NaPSS concentration, bubble collision velocity and polyelectrolyte molar
      mass. These measurements were then compared with an analytical model based on
      polyelectrolyte scaling theory in order to explain the effects of concentration
      and bubble deformation on the interaction between bubbles. Typically structural
      forces from the presence of monodisperse polyelectrolyte between interacting
      surfaces may be expected, however, it was found that the polydispersity in molar
      mass resulted in the structural forces to be smoothed and only a depletion
      interaction was able to be measured between interacting bubbles. It was found
      that an increase in number density of NaPSS molecules resulted in an increase in
      the magnitude of the depletion interaction. Conversely this interaction was
      overwhelmed by an increase in the fluid flow in the system at higher bubble
      collision velocities. Polymer molar mass dispersity plays a significant role in
      the interactions present between the bubbles and has implications that also
      affect the polyelectrolyte overlap concentration of the solution. Further
      understanding of these implications can be expected to play a role in the
      improvement in operations in such fields as water treatment and mineral
      processing where polyelectrolytes are used extensively. 

PMID- 25596871
TI  - Spinal near-infrared spectroscopy measurements during and after thoracoabdominal
      aortic aneurysm repair: a pilot study.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) is a noninvasive technique that
      allows continuous monitoring of regional hemoglobin oxygen saturation (rSo2). We
      evaluated its application to survey oxygenation of the spinal cord region during
      open thoracoabdominal aortic aneurysm (TAAA) repair and postoperatively in the
      intensive care unit (ICU). We also validated its association with motor-evoked
      potential (MEP) monitoring during the operation. METHODS: The rSo2 curves of 15
      patients (8 men; mean age, 64.2 +/- 7.7 years) were measured continuously with
      NIRS at spinal cord levels of the thoracic vertebrae T3 (optode 1, reference
      spot) and T12 (optode 2) during open TAAA repair. T12/T3 ratios were calculated.
      NIRS measurements were continued in the intensive care unit and stopped 24 hours
      after the operation. MEP monitoring was performed in all patients during the
      procedure. RESULTS: No clinical signs of spinal cord ischemia were documented in
      any of the patients. Continuous NIRS measurements were successfully performed in
      all patients during and after the operation. T12/T3 ratios were significantly
      lower in the MEP ratios that were less than 50% compared with the MEP ratios that
      were 50% or higher (p = 0.037). CONCLUSIONS: NIRS is an easily applicable
      noninvasive tool for continuous surveillance of oxygenation of the spinal cord
      region during TAAA repair and postoperatively in the intensive care unit. The
      rSo2 curves provide useful information concerning hemodynamic changes in
      oxygenation of the spinal cord region and might contribute to early detection of
      spinal cord ischemia. Further investigation is needed before broad clinical
      implementation.

PMID- 25596873
TI  - Distinct microRNA expression in endometrial lymphocytes, endometrium, and
      trophoblast during spontaneous porcine fetal loss.
AB  - Endometrial lymphocytes are recruited to the porcine maternal-fetal interface by
      conceptus-derived signals. The transiently recruited lymphocytes adopt a
      specialized phenotype in the endometrium that regulates various placental
      physiological processes, including angiogenesis. Small non-coding RNAs, microRNAs
      (miRNAs) are emerging as principal bio-molecules regulating the development of
      lymphocytes and their angiogenic functions. However, no information is available
      in the context of endometrial lymphocytes in pregnancy. We hypothesize that
      miRNAs are involved in the development of endometrial lymphocytes and their
      angiogenic functions at the porcine maternal-fetal interface. Using a targeted Q
      PCR approach for selected miRNAs involved in immune cell development,
      angiogenesis, and anti-angiogenesis, we conducted a study to screen endometrial
      lymphocytes associated with healthy and spontaneously arresting conceptus
      attachment sites (CAS) at two well-defined periods of fetal loss. Comparisons
      were made with endometrium and trophoblasts associated with healthy and arresting
      CAS. In addition, levels of putative mRNA targets and subsequent functional
      clustering of genes were studied in order to predict the biological mechanisms
      affected. We found several significant differences for miRNAs involved in immune
      cell development and angiogenesis (miR-296-5P, miR-150, miR-17P-5P, miR-18a, and
      miR-19a) between endometrial lymphocytes associated with healthy and arresting
      CAS. Significant differences were also found in endometrium and trophoblasts for
      some miRNAs (miR-20b, miR-17-5P, miR-18a, miR-15b-5P, and miR-222). Finally,
      selected mRNA targets showed differential expression in all groups. Our data,
      although associative, are the first to unravel the selected miRNAs involved in
      immune cell development and provide insights into their possible regulation in
      abortive pregnancy. 

PMID- 25596874
TI  - Undifferentiated (anaplastic) thyroid carcinoma: Practical immunohistochemistry
      and cytologic look-alikes.
AB  - Aspirate smears of undifferentiated (anaplastic) thyroid carcinoma (ATC) are, in
      most instances, readily recognized as malignant. Nonetheless, pitfalls exist with
      this neoplasm in part due to the absence of epithelial markers, overlapping
      features with other malignancies that may metastasize to or arise within the
      thyroid, and potential confusion with non-neoplastic conditions that simulate
      malignancy. We highlight the salient morphologic features of ATC and its
      variants, useful discriminatory ancillary immunostains to recognize it, and ATC
      mimickers that have the potential to confuse the cytopathologist. 

PMID- 25596875
TI  - Risk of stroke after chiropractic spinal manipulation in medicare B beneficiaries
      aged 66 to 99 years with neck pain.
AB  - OBJECTIVE: The purpose of this study was to quantify risk of stroke after
      chiropractic spinal manipulation, as compared to evaluation by a primary care
      physician, for Medicare beneficiaries aged 66 to 99 years with neck pain.
      METHODS: This is a retrospective cohort analysis of a 100% sample of annualized
      Medicare claims data on 1 157 475 beneficiaries aged 66 to 99 years with an
      office visit to either a chiropractor or primary care physician for neck pain. We
      compared hazard of vertebrobasilar stroke and any stroke at 7 and 30 days after
      office visit using a Cox proportional hazards model. We used direct adjusted
      survival curves to estimate cumulative probability of stroke up to 30 days for
      the 2 cohorts. RESULTS: The proportion of subjects with stroke of any type in the
      chiropractic cohort was 1.2 per 1000 at 7 days and 5.1 per 1000 at 30 days. In
      the primary care cohort, the proportion of subjects with stroke of any type was
      1.4 per 1000 at 7 days and 2.8 per 1000 at 30 days. In the chiropractic cohort,
      the adjusted risk of stroke was significantly lower at 7 days as compared to the
      primary care cohort (hazard ratio, 0.39; 95% confidence interval, 0.33-0.45), but
      at 30 days, a slight elevation in risk was observed for the chiropractic cohort
      (hazard ratio, 1.10; 95% confidence interval, 1.01-1.19). CONCLUSIONS: Among
      Medicare B beneficiaries aged 66 to 99 years with neck pain, incidence of
      vertebrobasilar stroke was extremely low. Small differences in risk between
      patients who saw a chiropractor and those who saw a primary care physician are
      probably not clinically significant.

PMID- 25596876
TI  - Propidium iodide (PI) stains Nissl bodies and may serve as a quick marker for
      total neuronal cell count.
AB  - Propidium iodide (PI) reacts with both DNA and RNA and is a commonly used
      fluorescent reagent for nucleic acid staining. The aim of the study was to
      compare the cellular staining patterns of PI with that of Nissl staining in rat
      nervous tissues and to report a modified staining method that selectively labels
      Nissl bodies in neurons. Cryosections and paraffin sections of different tissues
      of normal Sprague-Dawley rats, including trigeminal ganglia, dorsal root ganglia,
      spinal cord, liver, and small intestine, were stained by either PI or the
      hematoxylin and eosin method. Some sections were treated with RNase or DNase
      before the above staining, and some were double stained with PI and a Nissl
      stain. The sections were observed by light, fluorescence or confocal microscopy.
      Results showed strong PI signals detected as patterns of granules in the neuronal
      cytoplasm of all nervous tissues, whereas the staining of neuronal nuclei was
      weaker. In contrast, nuclei of neuroglial cells were strongly stained by PI,
      while the cytoplasm was not obviously stained. Pretreatment of the neural tissue
      with RNase abolished the PI signals. Furthermore, the PI positive granules in
      neuronal cytoplasm co-localized with Nissl bodies stained by the fluorescent
      Nissl stain. When the tissue was pretreated with DNase, PI only stained the
      cytoplasmic granules of neurons, but not that of glial cells. Our results show
      that PI stains Nissl bodies and may serve as an economical and convenient neuron
      marker for neuronal cell counting when specific neural markers such as antibodies
      are not readily available. 

PMID- 25596877
TI  - Effects of systemic Thalidomide and intracerebroventricular Etanercept and
      Infliximab administration in a Streptozotocin induced dementia model in rats.
AB  - Tumor necrosis factor-alpha (TNF-alpha) upregulation enhances amyloid beta
      (Abeta) induced neurotoxicity in Alzheimer's disease (AD).
      Intracerebroventricular streptozotocin (STZ) administration causes pathological
      changes and cognitive deficits similar to those seen in AD by causing impairment
      of brain glucose and energy metabolism. Recent reports indicate a protective role
      of Thalidomide, Etanercept, and Infliximab, all of which have anti-TNF-alpha
      activity, against cognitive and neuropathological changes in experimental and
      clinical studies. We aimed to investigate the protective effects of Thalidomide,
      Etanercept, and Infliximab in a rat model of intracerebroventricular STZ-induced
      dementia. Sprague-Dawley rats (250-300g) were separated to sham (n=6) and STZ
      (n=24) groups. The STZ group was divided into four groups (STZ, STZ-thalidomide,
      STZ-etanercept, and STZ-infliximab). Morris's water maze (MWM) and passive
      avoidance (PA) tests were performed. At the end of the third week, brain tissues
      were obtained. Histopathological analysis, immunohistochemistry, and electron
      microscopic examinations were done. The improvement performance of the STZ group
      was significantly reduced in the MWM test (p<0.001). Compared with the STZ, STZ
      thalidomide, STZ-etanercept, and STZ-infliximab groups had significantly better
      performance (p<0.001, <0.05 and <0.05, respectively) in the MWM test. STZ
      administration caused a significant decrease in the mean escape latency in PA
      reflex (p<0.001). Thalidomide, Etanercept, and Infliximab were associated with
      better PA reflexes compared to the STZ group (p<0.001 for all). Morphological and
      immunohistochemical results showed increased neurodegenerative changes compared
      to sham group. Our findings are in line with the findings reported in the
      literature and encourage further studies with TNF-alpha antagonists, in
      particular Thalidomide. 

PMID- 25596878
TI  - Palatal tremor in progressive supranuclear palsy: a case report.

PMID- 25596879
TI  - The 'Cognitions' index of the Parkinson's Disease Questionnaire-39 relates to
      sleep disturbance and hallucinations.

PMID- 25596880
TI  - Finger dexterity deficits in Parkinson's disease and somatosensory cortical
      dysfunction.
AB  - INTRODUCTION: The patho-physiological basis for finger dexterity deficits in
      Parkinson's disease (PD) is controversial. Previously, bradykinesia was regarded
      as the major mechanism. However, recent research suggested limb-kinetic apraxia
      as an important component of impaired fine motor skills in PD. In contrast to
      bradykinesia, limb-kinetic apraxia only marginally responds to dopaminergic
      treatment. Here we investigate the novel hypothesis that the dexterity deficits
      are related to an intrinsic dysfunction of primary somatosensory cortex (S1),
      which is not reversible by dopaminergic medication. METHODS: Applying a standard
      and approved dexterity task (coin rotation), brain activation networks were
      investigated using functional magnetic resonance imaging in PD patients both ON
      and OFF medication and matched healthy controls. RESULTS: PD patients both ON and
      OFF medication showed impaired S1 activation relative to controls (p < 0.05;
      region of interest based analysis). The impaired S1 activation remained unchanged
      by dopaminergic medication. Despite the considerable clinical deficit, no other
      brain area showed impaired activation. In contrast, structures of the basal
      ganglia--motor cortex loop responded to dopaminergic medication. Behaviorally,
      dexterity performance both ON and OFF was significantly (p < 0.05) reduced
      relative to controls. CONCLUSIONS: Our results provide first evidence that
      dexterity deficits in PD are related to an S1 dysfunction which is insensitive to
      dopaminergic treatment.

PMID- 25596882
TI  - Genetic predictive biomarkers of anti-VEGF treatment response in patients with
      neovascular age-related macular degeneration.
AB  - Anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age
      related macular degeneration (nAMD) have proven efficacy at a study-population
      level, although individual patient responses vary, with most of the patients
      responding well to anti-VEGF therapies, while a few respond poorly. The
      pathogenesis of AMD is known to have a genetic component, but it is unclear if
      any particular genotype can predict response to anti-VEGF therapy. With the
      advent of less expensive genotyping technology, there have been numerous studies
      within this area. Here we analyze potential biomarker candidates identified that
      could be used in a clinical setting to predict response to anti-VEGF treatment of
      nAMD. We analyze single nucleotide polymorphisms (SNPs) identified from 39
      publications. The SNPs that appeared to be of most importance fell into two main
      groups: those previously associated with AMD pathogenesis and those within the
      signaling pathway targeted by anti-VEGF therapies. A number of small studies
      found evidence supporting an association between anti-VEGF treatment response and
      two SNPs, CFH rs1061170 and VEGFA rs699947, but results from randomized
      controlled trials found no such association. It is possible that, in the future,
      the cumulative effect of several high-risk SNPs may prove useful in a clinical
      setting and that other genetic biomarkers may emerge. 

PMID- 25596881
TI  - CSF tau and tau/Abeta42 predict cognitive decline in Parkinson's disease.
AB  - INTRODUCTION: A substantial proportion of patients with Parkinson's disease (PD)
      have concomitant cognitive dysfunction. Identification of biomarker profiles that
      predict which PD patients have a greater likelihood for progression of cognitive
      symptoms is pressingly needed for future treatment and prevention approaches.
      METHODS: Subjects were drawn from the Deprenyl and Tocopherol Antioxidative
      Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled
      initially untreated PD patients. For the current study, Phase One encompassed
      trial baseline until just prior to levodopa administration (n = 403), and Phase
      Two spanned the initiation of levodopa treatment until the end of cognitive
      follow-up (n = 305). Correlations and linear mixed models were performed to
      determine cross-sectional and longitudinal associations between baseline amyloid
      beta1-42 (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau) in
      cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses
      also considered APOE genotype and tremor- vs. rigidity-dominant phenotype.
      RESULTS: No association was found between baseline CSF biomarkers and cognitive
      test performance during Phase One. However, once levodopa treatment was
      initiated, higher p-tau and p-tau/Abeta42 predicted subsequent decline on
      cognitive tasks involving both memory and executive functions. The interactions
      between biomarkers and cognition decline did not appear to be influenced by
      levodopa dosage, APOE genotype or motor phenotype. CONCLUSIONS: The current study
      has, for the first time, demonstrated the possible involvement of tau species,
      whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide
      association studies, in the progression of cognitive symptoms in PD.

PMID- 25596883
TI  - The pharmacodynamic properties of lurasidone and their role in its antidepressant
      efficacy in bipolar disorder.
AB  - The treatment of bipolar depression is one of the most challenging issues in
      contemporary psychiatry. Currently only quetiapine, the olanzapine-fluoxetine
      combination and recently lurasidone are officially FDA-approved against this
      condition. The neurobiology of bipolar depression and the possible targets of
      bipolar antidepressant therapy remain elusive. The current study investigated
      whether the pharmacodynamic properties of lurasidone fit to a previously
      developed model which was the first to be derived on the basis of the strict
      combination of clinical and preclinical data with no input from theory or
      opinion. The authors performed a complete and systematic review of the literature
      to identify the pharmacodynamic properties of lurasidone. The original model
      suggests that a constellation of effects on different receptors are necessary but
      the serotonin reuptake inhibition does not seem to play a significant role for
      bipolar depression. On the contrary norepinephrine activity seems to be very
      important. Probably the early antidepressant effect can be achieved through an
      agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A
      receptors, but the presence of a norepinephrine reuptake inhibition is essential
      in order to sustain it. Overall the properties of lurasidone fit well the model
      and add to its validity. A point that needs clarification is norepinephrine
      reuptake inhibition which is not yet studied for lurasidone.

PMID- 25596884
TI  - [Health-related quality of life in patients treated for ovarian cancer: tools and
      issues].
AB  - Health-related quality of life (QoL) in patients treated for ovarian cancer is
      directly and heavily impacted by the natural history of cancer, its evolution and
      its therapeutic modalities. The evaluation and consideration of various
      parameters of QoL seems to be a major issue. Indeed, on the one hand, it is
      essential to take into account the opinion of patients in the choice of
      therapeutic strategies for this cancer with a poor prognosis and, on the other
      hand, more and more studies show that QoL is an independent prognostic factor in
      ovarian cancer. Improvement in this case, in addition to being an endpoint by
      itself, would potentially improve the overall survival of patients. To date there
      are several tools to assess QOL of patients with ovarian cancer. The 2
      questionnaires most commonly used are: FACT-O and the EORTC QLQ-OV28. The aim of
      our study was to evaluate from a review of the literature, the reciprocal effects
      of ovarian cancer on QoL and QoL on ovarian cancer survival, as well as
      specificities of each of the 2 questionnaires most commonly used in assessing the
      QoL. 

PMID- 25596885
TI  - [Is surrogacy a crime against humanity or a treatment for uterine infertility?].

PMID- 25596886
TI  - The inverse autotransporter family: intimin, invasin and related proteins.
AB  - Intimin and invasin are adhesins and central virulence factors of attaching and
      effacing bacteria, such as enterohaemorrhagic Escherichia coli, and
      enteropathogenic Yersiniae, respectively. These proteins are prototypes of a
      large family of adhesins distributed widely in Gram-negative bacteria. It is now
      evident that this protein family represents a previously unrecognized
      autotransporter secretion system, termed type Ve secretion. In contrast to
      classical autotransport, where the transmembrane beta-barrel domain or
      translocation unit is C-terminal to the extracellular region or passenger domain,
      type Ve-secreted proteins have an inverted topology with the passenger domain C
      terminal to the translocation unit; hence the term inverse autotransporter. This
      minireview covers the recent advances in elucidating the structure and biogenesis
      of inverse autotransporters. 

PMID- 25596887
TI  - Peptidoglycan perception--sensing bacteria by their common envelope structure.
AB  - Most Eubacteria possess peptidoglycan (PGN) or murein that surrounds the
      cytoplasmic membrane. While on the one hand this PGN sacculus is a very
      protective shield that provides resistance to the internal turgor and adverse
      effects of the environment, it serves on the other hand as a major pattern of
      recognition due to its unique structure. Eukaryotes harness this particular
      bacterial macromolecule to perceive (pathogenic) microorganisms and initiate
      their immune defence. PGN fragments are generated by bacteria as turnover
      products during bacterial cell wall growth and these fragments can be sensed by
      plants and animals to assess a potential bacterial threat. To increase the
      sensitivity the concentration of PGN fragments can be amplified by host
      hydrolytic enzymes such as lysozyme or amidase. But also bacteria themselves are
      able to perceive information about the state of their cell wall by sensing small
      soluble fragments released from its PGN, which eventually leads to the induction
      of antibiotic responses or cell differentiation. How PGN is sensed by bacteria,
      plants and animals, and how the antibacterial defence is modulated by PGN
      perception is the issue of this review. 

PMID- 25596888
TI  - Biogenesis of beta-barrel proteins in evolutionary context.
AB  - The vast majority of outer membrane (OM) proteins in Gram-negative bacteria
      belongs to the class of membrane-embedded beta-barrel proteins. Besides Gram
      negative bacteria, the presence of beta-barrel proteins is restricted to the OM
      of the eukaryotic organelles mitochondria and chloroplasts that were derived from
      prokaryotic ancestors. The assembly of these proteins into the corresponding OM
      is in each case facilitated by a dedicated protein complex that contains a highly
      conserved central beta-barrel protein termed BamA/YaeT/Omp85 in Gram-negative
      bacteria and Tob55/Sam50 in mitochondria. However, little is known about the
      exact mechanism by which these complexes mediate the integration of beta-barrel
      precursors into the lipid bilayer. Interestingly, previous studies showed that
      during evolution, these complexes retained the ability to functionally assemble
      beta-barrel proteins from different origins. In this review we summarize the
      current knowledge on the biogenesis pathway of beta-barrel proteins in Gram
      negative bacteria, mitochondria and chloroplasts and focus on the commonalities
      and divergences that evolved between the different beta-barrel assembly
      machineries. 

PMID- 25596889
TI  - Excretion of cytosolic proteins (ECP) in bacteria.
AB  - Excretion of cytosolic proteins (ECP) has been reported in bacteria and
      eukaryotes. As none of the classical signal peptide (SP) dependent or SP
      independent pathways could be associated with ECP, it has been also referred to
      as 'non-classical protein export'. When microbiologists first began to study this
      subject in 1990, mainly singular cytoplasmic proteins were investigated, such as
      GAPDH at the cell surface and in the supernatant of pathogenic streptococci or
      glutamine synthetase (GlnA) as a major extracellular protein in pathogenic
      mycobacteria. Later, with the rising popularity of proteomics, it became obvious
      that the secretome of most bacteria contained a copious amount of cytosolic
      proteins. In particular ancient proteins such as glycolytic enzymes, chaperones,
      translation factors or enzymes involved in detoxification of reactive oxygen were
      found in the supernatants. As the excreted proteins do not possess a common
      motive, the most widespread opinion is that ECP is due to cell lysis. Indeed,
      upregulation of autolysins or distortion of the murein structure increased ECP,
      suggesting that enhanced ECP is some sort of survival strategy to counteract
      osmotic stress. However, in the meantime there are mounting evidences and hints
      that speak against cell lysis as a primary mechanism for ECP. Very likely, ECP
      belongs to the normal life cycle of bacteria and involves a programmed process.
      This review provides a brief overview of the 'non-classical protein export'. 

PMID- 25596890
TI  - The secrets of dermcidin action.
AB  - Antimicrobial peptides (AMPs) are important effector molecules of the innate
      immune defense of diverse species. The majority of known AMPs are cationic
      therefore facilitating the initial binding of the positively charged peptides to
      the negatively charged bacterial membrane. Dermcidin (DCD) is constitutively
      expressed in eccrine sweat glands, secreted into sweat and transported to the
      epidermal surface where it is proteolytically processed giving rise to several
      truncated DCD peptides. Its processed forms such as the anionic 48mer DCD-1L and
      the 47mer DCD-1 possess antimicrobial activity against numerous bacteria
      including Staphylococcus aureus. Here, the latest knowledge regarding the mode of
      action of the anionic DCD-1(L) and the functional consequences of their
      interaction with bacterial membranes is reviewed. There is evidence that the
      interaction of DCD-1(L) with negatively charged bacterial phospholipids leads to
      Zn(2+) dependent formation of oligomeric complexes in the bacterial membrane,
      which subsequently leads to ion channel formation resulting in membrane
      depolarization and bacterial cell death. 

PMID- 25596891
TI  - Seasonal variations of coastal sedimentary trace metals cycling: insight on the
      effect of manganese and iron (oxy)hydroxides, sulphide and organic matter.
AB  - The combination of analysis, multivariate treatment (PCA) and chemical speciation
      calculation confirmed the control of Fe, Mn, sulphide and organic matter on
      metals dynamics in coastal sediments (0-5 cm surface sediments and sediments
      cores) of Toulon Bay (NW Mediterranean). The temporal monitoring of the physic
      chemical parameters as well as the dissolved/particulate minor (Fe/Mn) and trace
      elements (i.e. Ag, Cd, Co, Cu, Ni, Pb, Zn, ...) concentrations in porewaters and
      sediments were assessed. Multivariate treatment revealed different behaviours for
      marine elements, terrestrial ones and contaminants. Seasonal variations of metals
      mobilization in porewater were observed, related to diagenesis activity. Element
      mobility was studied by selective extractions (ascorbate, acid and alkaline) on
      sediments. Thermodynamic simulation (PHREEQC) was performed to calculate the
      elemental dissolved speciation, the mineral saturation index and then to simulate
      the solid/liquid interaction through precipitation processes, studying the
      contrasted influence of dissolved organic matter and sulphide.

PMID- 25596892
TI  - Failure of the public health testing program for ballast water treatment systems.
AB  - Since 2004, an international testing program has certified 53 shipboard treatment
      systems as meeting ballast water discharge standards, including limits on certain
      microbes to prevent the spread of human pathogens. We determined how frequently
      certification tests failed a minimum requirement for a meaningful evaluation,
      that the concentration of microbes in the untreated (control) discharge must
      exceed the regulatory limit for treated discharges. In 95% of cases where the
      result was accepted as evidence that the treatment system reduced microbes to
      below the regulatory limit, the discharge met the limit even without treatment.
      This shows that the certification program for ballast water treatment systems is
      dysfunctional in protecting human health. In nearly all cases, the treatment
      systems would have equally well "passed" these tests even if they had never been
      turned on. Protocols must require minimum concentrations of targeted microbes in
      test waters, reflecting the upper range of concentrations in waters where ships
      operate. 

PMID- 25596894
TI  - Hospital acquired infections are falling, CDC reports.

PMID- 25596895
TI  - Validity and reliability of a simple, low-cost measure to quantify children's
      dietary intake in afterschool settings.
AB  - BACKGROUND: Interest in evaluating and improving children's diets in afterschool
      settings has grown, necessitating the development of feasible yet valid measures
      for capturing children's intake in such settings. OBJECTIVE: The purpose of this
      study was to test the criterion validity and cost of three unobtrusive visual
      estimation methods compared with a plate-weighing method: direct onsite
      observation using a 4-category rating scale and offsite rating of digital
      photographs taken onsite using 4- and 10-category scales. DESIGN: Researchers
      observed and photographed 174 total snack meals consumed across 2 days at each
      program. PARTICIPANTS/SETTING: Participants were 111 children in first through
      sixth grades attending four afterschool programs in Boston, MA, during December
      2011. STATISTICAL ANALYSIS: Visual estimates of consumption were compared to
      weighed estimates (the criterion measure) using intraclass correlations. RESULTS:
      All three methods were highly correlated with the criterion measure, ranging from
      0.92 to 0.94 for total calories consumed, 0.86 to 0.94 for consumption of
      prepackaged beverages, 0.90 to 0.93 for consumption of fruits/vegetables, and
      0.92 to 0.96 for consumption of grains. For water, which was not preportioned,
      coefficients ranged from 0.47 to 0.52. The photographic methods also demonstrated
      excellent interrater reliability: 0.84 to 0.92 for the 4-point and 0.92 to 0.95
      for the 10-point scale. The costs of the methods for estimating intake ranged
      from $0.62 per observation for the onsite direct visual method to $0.95 per
      observation for the criterion measure. CONCLUSIONS: Feasible, inexpensive methods
      can validly and reliably measure children's dietary intake in afterschool
      settings. Improving precision in measures of children's dietary intake can reduce
      the likelihood of spurious or null findings in future studies.

PMID- 25596896
TI  - Applying a nutrient-rich foods index algorithm to address nutrient content of
      food bank food.

PMID- 25596897
TI  - Healthy late preterm infants and supplementary artificial milk feeds: effects on
      breast feeding and associated clinical parameters.
AB  - OBJECTIVES: to compare the influence of supplementary artificial milk feeds on
      breast feeding and certain clinical parameters among healthy late preterm infants
      given regular supplementary artificial milk feeds versus being exclusively breast
      fed from birth. DESIGN: a comparative study using quantitative methods. Data were
      collected via a parental diary and medical records. METHODS: parents of 77 late
      preterm infants (34 5/7-36 6/7 weeks), whose mothers intended to breast feed,
      completed a diary during the infants' hospital stay. FINDINGS: infants who
      received regular supplementary artificial milk feeds experienced a longer delay
      before initiation of breast feeding, were breast fed less frequently and had
      longer hospital stays than infants exclusively breast fed from birth. Exclusively
      breast-fed infants had a greater weight loss than infants with regular artificial
      milk supplementation. A majority of the mothers (65%) with an infant prescribed
      artificial milk never expressed their milk and among the mothers who used a
      breast-pump, milk expression commenced late (10-84 hours after birth). At
      discharge, all infants were breast fed to some extent, 43% were exclusively
      breast fed. KEY CONCLUSIONS: clinical practice and routines influence the
      initiation of breast feeding among late preterm infants and may act as barriers
      to the mothers' establishment of exclusive breast feeding.

PMID- 25596898
TI  - Comment on: Validity of Minnesota Multiphasic Personality Inventory-2
      Restructured Form (MMPI-2-RF) scores as a function of gender, ethnicity, and age
      of bariatric surgery candidates.

PMID- 25596899
TI  - Children's emergency department use for asthma, 2001-2010.
AB  - OBJECTIVES: Although the emergency department (ED) provides essential care for
      severely ill or injured children, past research has shown that children often
      visit the ED for potentially preventable illnesses, including asthma. We sought
      to determine how children's rate of ED visits for asthma has changed over the
      last decade and to analyze what factors are associated with a child's potentially
      preventable ED visit for asthma. METHODS: We retrospectively analyzed ED visits
      by children aged 2 to 17 from 2001 to 2010 using data from the National Hospital
      Ambulatory Medical Care Survey. Visits were classified as potentially preventable
      asthma visits by mapping ICD-9-CM diagnosis codes to the Agency for Healthcare
      Research and Quality's asthma pediatric quality indicator. We examined trends in
      the annual rate of ED visits for asthma per 1000 children using a weighted linear
      regression model. Finally, we used multivariate logistic regression to determine
      what demographic, clinical, and structural factors were associated with a child's
      ED visit being for a potentially preventable asthma crisis. RESULTS: The rate of
      children's ED visits for asthma increased 13.3% between 2001 and 2010, from 8.2
      to 9.3 visits per 1000 children (P = .26). ED visits by children who were
      younger, male, racial or ethnic minorities, insured with Medicaid/Children's
      Health Insurance Program, and visiting between 11 pm and 7 am were more likely to
      be for potentially preventable asthma crises. CONCLUSIONS: Although the overall
      rate of potentially preventable ED visits for asthma did not significantly change
      over the last decade, racial, insurance-based, and other demographic disparities
      in the likelihood of a preventable asthma-related ED visit persist.

PMID- 25596900
TI  - Factors associated with quality of life in active childhood epilepsy: a
      population-based study.
AB  - BACKGROUND: Improving health-related quality of life (HRQOL), rather than just
      reducing seizures, should be the principal goal in comprehensive management of
      childhood epilepsy. There is a lack of population-based data on predictors of
      HRQOL in childhood epilepsy. METHODS: The Children with Epilepsy in Sussex
      Schools (CHESS) study is a prospective, population-based study involving school
      aged children (5-15 years) with active epilepsy (on one or more AED and/or had a
      seizure in the last year) in a defined geographical area in the UK. Eighty-five
      of 115 (74% of eligible population) children underwent comprehensive
      psychological assessment including measures of cognition, behaviour, and motor
      functioning. Parents of the children completed the Quality of Life in Childhood
      Epilepsy (QOLCE).Clinical data on eligible children was extracted using a
      standardised pro forma. Linear regression analysis was undertaken to identify
      factors significantly associated with total Quality of Life in this population.
      RESULTS: Factors independently significantly associated (p < .05) with total
      QOLCE scores were seizures before 24 months, cognitive impairment (IQ < 85),
      anxiety, and parent reported school attendance difficulty. These factors were
      also significantly associated with total QOLCE when children with IQ < 50 were
      excluded from analysis. CONCLUSIONS: The majority of factors associated with
      parent reported HRQOL in active childhood epilepsy are related to
      neurobehavioural and/or psychosocial aspects of the condition.

PMID- 25596901
TI  - Child apolipoprotein E gene variants and risk of cerebral palsy: estimation from
      case-parent triads.
AB  - OBJECTIVE: To use case-parent triad data to investigate if cerebral palsy (CP) is
      associated with variants of the APOE gene, the rs59007384 SNP of the TOMM40 gene
      or combined haplotypes of the two genes. STUDY DESIGN: DNA was analyzed in buccal
      swabs from 235 children with CP, their parents and a sibling. The relative risks
      (RR) with 95% confidence intervals (CI) that the children would have a
      distribution of APOE genotypes, rs59007384 variants or combined haplotypes
      deviating from Mendelian inheritance were estimated. RESULTS: Children with CP
      were more likely than expected to carry the APOEepsilon3 allele (RR 7.5; CI: 0.99
      53.7 for heterozygotes and 10.3; CI: 1.4-79.6 for homozygotes), and to have the
      haplotype of APOEepsilon3 and rs59007384 G (RR 2.4; CI: 1-5.7 for heterozygotes,
      RR 3.7; CI: 1.4-9.5 for homozygotes) whereas the distribution was as expected for
      rs59007384 alone. In the subgroup analyses the findings were confined to children
      born preterm. Among siblings the distribution of these genes was as expected
      according to Mendelian inheritance. CONCLUSION: We speculate that children with
      APOEepsilon2/APOEepsilon4 alleles are more likely to die following cerebral
      injury in utero, resulting in a higher than expected proportion of children with
      CP carrying the APOEepsilon3 allele.

PMID- 25596902
TI  - Alterations in the trapezius muscle in young patients with migraine--a pilot case
      series with MRI.
AB  - BACKGROUND/PURPOSE: Migraine is frequent in young adults and adolescents and
      often associated with neck muscle tension and pain. Common pathophysiological
      pathways, such as reciprocal cervico-trigeminal activation, are assumed. Tense
      areas within the neck muscles can be clinically observed many patients with
      migraine. The aim of this pilot case study was to visualize these tense areas via
      magnet resonance imaging (MRI). METHODS: Three young patients with migraine were
      examined by an experienced investigator. In all three patients tense areas in the
      trapezius muscles were palpated. These areas were marked by nitroglycerin
      capsules on the adjacent skin surface. RESULTS: The MRI showed focal signal
      alterations at the marked locations within the trapezius muscles. CONCLUSION:
      Visualization of palpable tense areas by MRI may be usefully applied in the
      future to help elucidate the underlying pathophysiological processes of migraine.

PMID- 25596903
TI  - Efficacy of Ovarian Artery Embolization for Uterine Fibroids: Clinical and
      Magnetic Resonance Imaging Evaluations.
AB  - PURPOSE: The objective of the study was to assess the efficacy of ovarian artery
      embolization (OAE) treatment for symptomatic uterine leiomyomas. METHODS: A
      retrospective review of 17 patients who underwent OAE in conjunction with uterine
      artery embolization in a 6-year period (2006-2012) was performed. Ten patients
      had previous failed embolization, while 7 had not received any embolization
      therapy before. Percent uterine volume change, percent dominant fibroid volume
      change, and percent dominant fibroid infarction were assessed with magnetic
      resonance (MR) imaging. Resolution of menorrhagia, dysmenorrhea/pain, and bulk
      and/or pressure symptoms including urinary frequency were evaluated clinically.
      Change in menopausal state was also an outcome of interest. RESULTS: Mean MR
      imaging follow-up was performed 3 months post-OAE. MR images showed complete
      infarction in the majority of cases (64.7%; n = 11), with infarction rates of 90%
      100% in 3 cases, 1 case with 30%-50% infarction, and 2 cases with 0%-10%
      infarction. Average uterine size reduction on MR was 32.3% (95% confidence
      interval [CI]: 22.5%-42.2%; P < .001). The average size reduction for the
      dominant fibroid was 42.4% (95% CI: 27.7%-57.0%; P = .01). The mean time to final
      follow-up visit was 11 months. At this point complete symptom resolution
      (menorrhagia, dysmenorrhea and bulk-related) was achieved in 82.4% (n = 14) of
      cases. At the final follow-up 11.8% (n = 2) of cases reported menopause.
      CONCLUSIONS: We observed OAE to be an effective and safe adjunct to uterine
      artery embolization when hypertrophic ovarian artery(ies) require intervention.
      However, incomplete fibroid infarction of 23% remains a concern with a potential
      for long-term treatment failure. In addition, long-term effect on ovarian
      function is uncertain.

PMID- 25596904
TI  - Live birth after artificial oocyte activation using a ready-to-use ionophore: a
      prospective multicentre study.
AB  - Artificial oocyte activation has been proposed as a suitable means to overcome
      the problem of failed or impaired fertilization after intracytoplasmic sperm
      injection (ICSI). In a multicentre setting artificial oocyte activation was
      applied to 101 patients who were diagnosed with fertilization abnormalities (e.g.
      less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female
      gametes were activated for 15 min immediately after ICSI using a ready-to-use
      Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates
      were compared with the preceding cycle without activation. The fertilization rate
      of 48% in the study cycles was significantly higher compared with the 25% in the
      control cycles (P < 0.001). Further splitting of the historical control group
      into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed
      that all groups significantly benefitted (P < 0.001) in the ionophore cycle.
      Fewer patients had their embryo transfer cancelled compared with their previous
      treatments (1/101 versus 15/101). In total, 99% of the patients had an improved
      outcome with A23187 application resulting in a 28% live birth rate (35 babies).
      These data suggest that artificial oocyte activation using a ready-to-use
      compound is an efficient method. 

PMID- 25596905
TI  - Can repeated IVF-ICSI-cycles be avoided by using blastocysts developing from poor
      quality cleavage stage embryos?
AB  - In many clinics, good-quality embryos are selected for embryo transfer and
      cryopreservation at the cleavage stage, and poor-quality embryos are discarded.
      The aim of this retrospective study was to examine how many repeated IVF cycles
      could be avoided by culturing the cleavage stage poor-quality embryos to
      blastocyst stage and transferring them after vitrification and warming (604 IVF
      and intracytoplasmic sperm injection [IVF-ICSI] cycles were included). Poor
      quality cleavage stage embryos not eligible for transfer or cryopreservation were
      cultured until day 5 or 6, and those developing to the blastocyst stage were
      vitrified. The rate of vitrified blastocysts and clinical pregnancy and delivery
      rate of the warmed blastocysts was evaluated. The effect of the extended culture
      on the cumulative delivery rate, and the number of avoided new treatment cycles
      was calculated. The surplus blastocysts resulted in clinical pregnancy,
      spontaneous abortion and delivery rates of 24.6%, 27.3% and 17.2% respectively.
      The use of surplus blastocysts raised cumulative delivery rate from 43% to 47%
      and 53 repeated new cycles were avoided. This study shows that the cumulative
      delivery rate can be increased, and repeated IVF-ICSI treatments avoided by using
      blastocysts developing from poor-quality cleavage stage embryos, which otherwise
      would have been discarded. 

PMID- 25596906
TI  - Once you're choosing, nobody's perfect: is more information necessarily better in
      oocyte donor selection?
AB  - Despite a growing body of research examining the psychosocial issues involved in
      oocyte donation, few studies have examined the role of information in the process
      of donor selection. The aim of this interview-based qualitative study was to
      understand how donor oocyte recipients relate to information provided about
      potential oocyte donors, how they use this information to select donors and their
      preferences for, and reactions to, various types of information provided to them.
      Donor oocyte recipients who underwent treatment between 1995 and 2011 were
      recruited for participation from an academic centre for reproductive medicine.
      Twenty-two oocyte donor recipients participated. Findings indicate that
      recipients use information to select donors who they believe would enable them to
      fulfill their priorities: having a healthy child and 'passing' as genetically
      related. Obtaining more specific information prompted a focus on donor
      imperfections and presented a burden of choosing. Moreover, for participants
      preferring distance, having more information created dilemmas by making the
      donors less abstract. Although more information and options are often desired by
      oocyte donor recipients, increased choice can also present psychological dilemmas
      and emotional costs. Further research is needed to investigate the influence of
      information-related conflicts on patient decision-making, post-treatment
      emotional adjustment and disclosure decisions. 

PMID- 25596907
TI  - Association between KIAA0319L, PXK and JAZF1 gene polymorphisms and unexplained
      recurrent pregnancy loss in Chinese Han couples.
AB  - KIAA0319L, PXK and JAZF1 gene polymorphisms were investigated to determine
      whether they conferred susceptibility to unexplained recurrent pregnancy loss
      (URPL) in a group of Chinese Han patients. Genotyping and sequencing of the
      single nucleotide polymorphisms (SNP) rs2275247(A/G) in KIAA0319L, rs2176082(C/T)
      and rs6445975(G/T) in PXK and the rs1635852(C/T) in JAZF1 were carried out in 84
      couples with URPL and 102 healthy couples with at least one live birth.
      Frequencies of the SNP rs2176082(C/T) in PXK gene were significantly different
      between women with URPL and control women: P < 0.05; OR 95% CI 0.530 (0.287 to
      0.979); OR 95% CI 0.482 (0.254 to 0.911) but were not significantly different
      after Bonferroni correction. The frequencies of the SNP rs2176082(C/T) in PXK
      gene showed no difference between the husband of a woman with URPL and a control
      husband: OR 95% CI 1.494 (0.821 to 2.721); OR 95% CI 1.567 (0.841 to 2.921). No
      statistically significant differences were observed in the distribution of any
      genotype or allele frequency or any genetic model of the other three SNPs between
      couples with URPL and control couples. Therefore, the rs2176082(C/T) polymorphism
      of PXK might play a possible role in the development of URPL in Chinese Han
      women. 

PMID- 25596908
TI  - Semen decontamination for the elimination of seminal HIV-1.
AB  - The risk of human immunodeficiency virus (HIV) transmission to the female
      partner, or potential offspring of an HIV-1 infected man can be reduced using
      semen decontamination procedures before assisted reproductive treatment (ART).
      The objective of this study was to determine the efficiency of decontaminating
      semen samples (n = 186) from 95 HIV-1 sero-positive patients. Aliquots of neat
      semen were submitted for viral validation by qualitative and quantitative
      polymerase chain reaction. Semen samples were processed by density gradient
      centrifugation in combination with a ProInsertTM tube after which aliquots of the
      processed sperm samples were analysed for the presence of HIV-1. Fifty-four
      percent of all tested neat semen samples tested positive for HIV-1 DNA, RNA or
      both (13.4%, 11.3% and 29.0%, respectively). From a total of 103 processed sperm
      samples that were submitted for viral validation, two samples tested positive for
      HIV-1 DNA and none for RNA. In conclusion, semen processing with the ProInsertTM
      followed by viral validation of processed sperm samples should be carried out
      when providing ART to couples where the male partner is HIV-1 sero-positive.

PMID- 25596909
TI  - Evaluation of the role of maternal serum high-sensitivity C-reactive protein in
      predicting early pregnancy failure.
AB  - Maternal serum high-sensitivity C-reactive protein (HSCRP) was evaluated in
      predicting spontaneous abortion in spontaneous pregnancies presenting with
      threatened spontaneous abortion. Seventy-one cases of threatened spontaneous
      abortion (group A) and 71 asymptomatic controls (group B), matched for
      gestational and maternal age, body mass index and smoking status, were included.
      Maternal serum samples were evaluated for HCG, progesterone, pregnancy-associated
      plasma protein-A (PAPP-A) and HSCRP using standard bio-assays. No difference was
      observed in ultrasound measurements, and median progesterone maternal serum level
      was significantly lower (P < 0.05) in group A compared with group B. In group A,
      the median of all ultrasound and maternal serum parameters was significantly
      lower (P < 0.01) compared with group B. The median gestational sac diameter,
      volume and median HSCRP and PAPP-A levels were significantly increased (P < 0.05)
      in group A, with a normal outcome compared with group B, probably owing to the
      inflammatory reaction associated with intrauterine bleeding. In group A patients
      destined to abortion, the gestational sac development and corresponding protein
      synthesis fell before the fetal heart activity stopped; in spontaneous
      pregnancies, maternal serum HSCRP did not provide additional information for the
      management of threatened spontaneous abortion but warrants further research in
      assisted reproduction pregnancies. 

PMID- 25596912
TI  - The role of boost and hypofractionation as adjuvant radiotherapy in patients with
      DCIS: a meta-analysis of observational studies.
AB  - PURPOSE: The purpose of this meta-analysis is to summarize the current evidence
      on the role of boost and the efficacy of hypofractionated radiotherapy in
      patients with ductal cancer in situ (DCIS) after surgery and grade the quality of
      evidence. MATERIALS AND METHODS: A comprehensive systematic electronic search
      through MEDLINE and the Cochrane Library as well as through the major
      international congresses' proceedings was conducted. Studies were considered
      eligible if they investigated the efficacy of hypofractionated vs. standard
      radiotherapy or the efficacy of boost vs. no boost in patients with DCIS. The
      outcome of interest was the number of local recurrences. Pooled estimates were
      calculated by using standard meta-analytic procedures. RESULTS: Thirteen trials
      were considered eligible and were further analyzed. No difference in the risk of
      local recurrence was observed between the patients that received boost vs. no
      boost in the general cohort (12 studies, 6943 patients; Odds Ratio (OR): 0.91,
      95% confidence interval (CI): 0.77-1.08, very low level of evidence). However, we
      found a reduced risk for local recurrence when boost was administered in patients
      with positive margins compared to no boost (6 studies, 811 patients; OR: 0.56,
      95% CI: 0.36-0.87, very low level of evidence). No difference in local recurrence
      rate between patients who received hypofractionated versus standard radiotherapy
      was observed (4 studies, 2534 patients; OR: 0.78, 95% CI: 0.58-1.03, low level of
      evidence). CONCLUSION: Hypofractionated radiotherapy seems to be a safe option in
      patients with DCIS after breast-conserving surgery while the addition of boost
      reduces the risk for local recurrence in the presence of positive margins.
      However, the level of evidence for these observations ranges between very low and
      low and the results of the ongoing randomized trials are necessary to confirm the
      results with higher level of evidence.

PMID- 25596911
TI  - Antidepressants may lead to a decrease in niacin and NAD in patients with poor
      dietary intake.
AB  - The term niacin is the generic name for the two compounds nicotinic acid and
      nicotinamide, the major dietary precursors for two important coenzymes,
      nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP. Niacin
      is important for the maintenance of cellular integrity and energy production and
      is involved in more than 500 intracellular reactions. Deficiencies of niacin may
      contribute to neuropsychiatric and neurodegenerative disorders. Patients who
      develop nutritional deficiencies as a result of poor dietary intake, especially
      inadequate intake of proteins and vitamins, could potentially suffer from niacin
      deficiency and NAD depletion. However, de novo synthesis of niacin and NAD in the
      kynurenine pathway of tryptophan metabolism may compensate for impaired dietary
      intake. The rate of synthesis of NAD and niacin from tryptophan oxidation depends
      on the induction of the enzyme indoleamine 2,3-dioxygenase (IDO) by pro
      inflammatory cytokines such as interferon-gamma. Niacin synthesis is not limited
      by a decrease in tryptophan and excessive IDO activity may therefore lead to a
      decline in tryptophan levels. Antidepressants have an anti-inflammatory effect,
      including reduction of interferon-gamma and therefore inhibition of IDO, the rate
      limiting enzyme of the kynurenine pathway. In theory, this could account for
      increased serotonin as more tryptophan becomes available for serotonin synthesis.
      However, the downside may be that less NAD and niacin are synthesised downstream,
      which could exacerbate common psychiatric problems. It is our hypothesis that
      patients with poor dietary intake, who are treated with antidepressants, are at
      risk of developing niacin/NAD deficiency with possible development of associated
      neuropsychiatric symptoms. We therefore propose that niacin supplementation be
      considered in patients with inadequate diets who are treated with
      antidepressants. We believe that if this does not happen, a subclinical niacin
      deficiency may result, which would be difficult to detect as it would cause the
      same symptoms of the original illness (e.g. depression). Niacin deficiency should
      be considered and ruled out in all patients with treatment-resistant depression,
      who have a poor response to antidepressants. This is potentially a cost-effective
      and easy intervention, which could be examined in a randomized controlled trial. 

PMID- 25596910
TI  - Randomized, controlled, open-label, non-inferiority study of the CONSORT
      algorithm for individualized dosing of follitropin alfa.
AB  - In this randomized, controlled, open-label, phase IV study, ovarian response
      after a follitropin alfa starting dose determined by the CONSORT calculator was
      compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years)
      eligible for assisted reproductive techniques were recruited (23 centres: nine
      European countries and Chile); 200 women were randomized (CONSORT [n = 96];
      standard dosing [n = 104]). Significantly lower mean daily (121.5 versus 167.4
      IU; P < 0.001) and total (1288.5 versus 1810.0 IU; P < 0.001) doses of
      follitropin alfa were administered in the CONSORT group. Clinical pregnancy rates
      were CONSORT (36.0%) and standard dosing (35.5%); estimated difference
      (confidence interval 0.6%; -13.5 to 14.6). Ovarian hyperstimulation syndrome
      occurred in 6.3% and 12.5% of patients in the CONSORT and standard-dosing groups,
      respectively. The primary efficacy analysis found a significantly lower mean [SD]
      number of oocytes retrieved in the CONSORT (10.0 [5.6]; P = 0.037) versus
      standard-dosing group (11.8 [5.3]). Although the CONSORT calculator was
      statistically inferior to standard dosing in the number of oocytes retrieved,
      clinical pregnancy rates (fresh embryo transfers) were similar in both groups,
      and incidence of ovarian hyperstimulation syndrome was lower in the CONSORT
      group.

PMID- 25596913
TI  - Brain abnormalities on MRI in non-functioning pituitary adenoma patients treated
      with or without postoperative radiotherapy.
AB  - BACKGROUND AND PURPOSE: To assess and compare brain abnormalities on Magnetic
      Resonance Imaging (MRI) in non-functioning pituitary macro-adenoma (NFA) patients
      treated with or without postoperative radiotherapy (RT). MATERIAL AND METHODS: In
      86 NFA patients, treated between 1987 and 2008 at the University Medical Center
      Groningen, white-matter lesions (WMLs), cerebral atrophy, brain infarctions and
      abnormalities of the temporal lobes and hippocampi were assessed on pre- and post
      treatment MRI scans in patients treated with (n=47) or without RT. RESULTS: The
      median MRI follow-up time for RT patients was 10 (range 1-22) years and 5 (range
      1-21) years in patients treated without RT. In RT patients the cumulative
      incidence of WMLs was significantly lower compared to patients treated without RT
      (log-rank test RR 0.49, 95% CI 0.25-0.97, p=.042). The cumulative incidences of
      cerebral atrophy, brain infarctions, abnormalities of the temporal lobes and
      hippocampi, and the severity of WMLs and cerebral atrophy ratings were not
      significantly different between the two treatment groups. CONCLUSIONS: Brain
      abnormalities on MRI are not observed more frequently in NFA patients treated
      with RT compared to patients treated with surgery-alone. Furthermore, RT was not
      associated with an increased severity of WMLs and cerebral atrophy ratings in
      this cohort of NFA patients.

PMID- 25596914
TI  - Regional recurrence after adjuvant breast cancer radiotherapy is not due to
      insufficient target coverage.

PMID- 25596915
TI  - Mammographic compression--a need for mechanical standardization.
AB  - BACKGROUND: A lack of consistent guidelines regarding mammographic compression
      has led to wide variation in its technical execution. Breast compression is
      accomplished by means of a compression paddle, resulting in a certain contact
      area between the paddle and the breast. This procedure is associated with varying
      levels of discomfort or pain. On current mammography systems, the only mechanical
      parameter available in estimating the degree of compression is the physical
      entity of force (daN). Recently, researchers have suggested that pressure (kPa),
      resulting from a specific force divided by contact area on a breast, might be a
      more appropriate parameter for standardization. Software has now become available
      which enables device-independent cross-comparisons of key mammographic metrics,
      such as applied compression pressure (force divided by contact area), breast
      density and radiation dose, between patient populations. PURPOSE: To compare the
      current compression practice in mammography between different imaging sites in
      the Netherlands and the United States from a mechanical point of view, and to
      investigate whether the compression protocols in these countries can be improved
      by standardization of pressure (kPa) as an objective mechanical parameter.
      MATERIALS AND METHODS: We retrospectively studied the available parameters of a
      set of 37,518 mammographic compressions (9188 women) from the Dutch national
      breast cancer screening programme (NL data set) and of another set of 7171
      compressions (1851 women) from a breast imaging centre in Pittsburgh, PA (US data
      set). Both sets were processed using VolparaAnalytics and VolparaDensity to
      obtain the applied average force, pressure, breast thickness, breast volume,
      breast density and average glandular dose (AGD) as a function of the size of the
      contact area between the breast and the paddle. RESULTS: On average, the forces
      and pressures applied in the NL data set were significantly higher than in the US
      data set. The relative standard deviation was larger in the US data set than in
      the NL data set. Breasts were compressed with a force in the high range of >15
      daN for 31.1% and >20 kPa for 12.3% of the NL data set versus, respectively, 1.5%
      and 1.7% of the US data set. In the low range we encountered compressions with a
      pressure of <5 daN for 21.1% and <5 kPa for 21.7% of the US data set versus,
      respectively, 0.05% and 0.6% in the NL data set. Both the average and the
      standard deviation of the AGD were higher in the US data set. CONCLUSION: (1)
      Current mammographic breast compression policies lead to a wide range of applied
      forces and pressures, with large variations both within and between clinical
      sites. (2) Pressure standardization could decrease variation, improve
      reproducibility, and reduce the risk of unnecessary pain, unnecessary high
      radiation doses and inadequate image quality.

PMID- 25596917
TI  - Di(2-ethylhexyl) phthalate biodegradation and denitrification by a
      Pseudoxanthomonas sp. strain.
AB  - A bacterial strain (designated as N4) of Pseudoxanthomonas was isolated from a
      denitrification biofilter reactor. This study examined its degradation capability
      of di(2-ethylhexyl) phthalate (DEHP) and its denitrification ability. All results
      showed that, strain N4 could use DEHP as a carbon and energy source. Strain N4
      demonstrated good DEHP degradation ability over a broad pH and temperature range.
      The optimal temperature and pH for DEHP degradation were 32 degrees C and 6.0,
      respectively. The kinetics of DEHP degradation by strain N4 were exponential in
      nature. Strain N4 showed denitrification ability and could reduce nitrate and
      nitrite but not with DEHP as its carbon source. 

PMID- 25596916
TI  - Effect of different reconstruction algorithms on computer-aided diagnosis (CAD)
      performance in ultra-low dose CT colonography.
AB  - PURPOSE: To assess the effect of different reconstruction algorithms on computer
      aided diagnosis (CAD) performance in ultra-low-dose CT colonography (ULD CTC).
      MATERIALS AND METHODS: IRB approval and informed consents were obtained. Thirty
      prospectively enrolled patients underwent non-contrast CTC at 120 kVp/10 mAs in
      supine and 100 kVp/10 mAs in prone positions, followed by same-day colonoscopy.
      Images were reconstructed with filtered back projection (FBP), 80% adaptive
      statistical iterative reconstruction (ASIR80), and model-based iterative
      reconstruction (MBIR). A commercial CAD system was applied and per-polyp
      sensitivities and numbers of false-positives (FPs) were compared among
      algorithms. RESULTS: Mean effective radiation dose of CTC was 1.02 mSv. Of 101
      polyps detected and removed by colonoscopy, 61 polyps were detected on supine and
      on prone CTC datasets on consensus unblinded review, resulting in 122 visible
      polyps (32 polyps<6 mm, 52 6-9.9 mm, and 38>=10 mm). Per-polyp sensitivity of CAD
      for all polyps was highest with MBIR (56/122, 45.9%), followed by ASIR80 (54/122,
      44.3%) and FBP (43/122, 35.2%), with significant differences between FBP and IR
      algorithms (P<0.017). Per-polyp sensitivity for polyps>=10 mm was also higher
      with MBIR (25/38, 65.8%) and ASIR80 (24/38, 63.2%) than with FBP (20/38, 58.8%),
      albeit without statistical significance (P>0.017). Mean number of FPs was
      significantly different among algorithms (FBP, 1.4; ASIR, 2.1; MBIR, 2.4)
      (P=0.011). CONCLUSION: Although the performance of stand-alone CAD for ULD CTC
      can be improved, IR algorithms, particularly MBIR, were shown to significantly
      increase the per-polyp sensitivity of CAD compared to FBP according to this
      study. Therefore, as ULD CTC only requires 1.02mSv, specific optimization of CAD
      for ULD CTC and IR algorithms is strongly warranted to make ULD CTC with CAD
      clinically viable.

PMID- 25596918
TI  - Pulmonary artery dissection in eight dogs with patent ductus arteriosus.
AB  - OBJECTIVES: To describe a series of dogs with pulmonary artery dissection and
      patent ductus arteriosus (PDA). ANIMALS: Eight dogs. METHODS: Retrospective case
      series. RESULTS: Pulmonary artery dissection was diagnosed in 8 dogs, 3 were
      Weimaraners. Four dogs presented in left-sided congestive heart failure, 4
      presented for murmur evaluation and without clinical signs, and 1 presented in
      right-sided congestive heart failure. In 7 dogs the dissection was first
      documented concurrent with a diagnosis of uncorrected PDA. In the other dog, with
      pulmonary valve stenosis and PDA, the dissection was observed on autopsy
      examination 17 months after balloon pulmonary valvuloplasty and ductal closure.
      Median age at presentation for the 7 dogs with antemortem diagnosis of pulmonary
      artery dissection was 3.5 years (range, 1.5-4 years). Three dogs had the PDA
      surgically ligated, 2 dogs did not undergo PDA closure, 1 dog failed
      transcatheter occlusion of the PDA with subsequent surgical ligation, 1 dog
      underwent successful transcatheter device occlusion of the PDA, and 1 dog had the
      PDA closed by transcatheter coil delivery 17 months prior to the diagnosis of
      pulmonary artery dissection. The 2 dogs that did not have the PDA closed died 1
      and 3 years after diagnosis due to heart failure. CONCLUSIONS: Pulmonary artery
      dissection is a potential complication of PDA in dogs, the Weimaraner breed may
      be at increased risk, presentation is often in mature dogs, and closure of the
      PDA can be performed and appears to improve outcome.

PMID- 25596919
TI  - Hsp90, Hsp60 and HSF-1 genes expression in muscle, heart and brain of thermally
      manipulated broiler chicken.
AB  - The effect of thermal manipulation (TM) during embryogenesis (ED 12-18) on mRNA
      expressions of heat shock proteins (Hsp90, Hsp60 and HSF-1) in muscle, heart and
      brain tissues during thermal challenge (TC) at post-hatching days 10 and 28 was
      investigated. Fertile chicken eggs were randomly divided into four groups:
      Control group (37.8  degrees C), TM1 (39  degrees C for 9 h), TM2 (39  degrees C
      for 12 h) and TM3 (39  degrees C for 18 h). At days 10 and 28 of age, chicks in
      TC groups were subjected to thermal challenge (TC) at 43.0  degrees C for 6 h
      while naive chicks were kept under regular conditions. When compared with the
      control, TM resulted in a significant increase in mRNA levels of Hsp90, Hsp60 and
      HSF-1in muscle, heart and brain tissues during embryogenesis and during TC at
      days 10 and 28 post-hatching. These results indicate a long-term enhancement of
      Hsp90, Hsp60 and HSF-1 gene expressions associated with improved thermotolerance
      acquisition in thermally manipulated chicks. 

PMID- 25596920
TI  - Validation of an activity monitor during sleep in patients with chronic
      respiratory disorders.
AB  - INTRODUCTION: Objective of this study was to validate an activity monitor
      (DynaPort MoveMonitor [MM], McRoberts, The Hague, The Netherlands) against night
      vision video analysis during sleep. METHODS: Twenty patients (65 +/- 11 years
      old, mean body-mass-index: 27 +/- 6 kg/m(2)) with different chronic lung diseases
      were recruited to participate in this validation study. Patients performed a
      polysomnography measurement during one single night while wearing the MM. The
      activity monitor data of the MM were then validated against the analysis of the
      night-vision video by an independent investigator. In total, four different lying
      positions (supine, left, right and prone), sitting upright, out of bed as well as
      large, medium, small and sitting transitions were classified. RESULTS: A mean
      duration of 7.6 +/- 0.9 h per night of video and MM classification was available
      for analysis. In total, 702 different postures were registered on the video from
      which 678 postures (96.6%) were detected correctly by the MM compared to the
      video classification. These results yielded a total degree of sensitivity of
      93.9% and specificity 94.9% in detecting postures during the night. In total, 682
      transitions (394 small, 189 medium, 15 large and 84 sitting transitions) were
      detected of which 482 were also detected by the MM. The MM detected 70% of the
      transitions correctly (51.0% small, 97.4% medium, 100% large and 97.6% sitting
      transitions). CONCLUSION: The MM is an activity monitor showing a high degree of
      sensitivity and specificity to detect different nocturnal postures as well as
      medium and large sized transitions in patients with chronic respiratory
      disorders.

PMID- 25596921
TI  - [Monoclonal gammopathies of undetermined significance do not systematically
      require a specialized consultation].
AB  - INTRODUCTION: Monoclonal gammopathy of undetermined significance (MGUS) is a
      frequent entity in the general population. The incidence rate of fortuitous
      discovery of a monoclonal component in asymptomatic patients is increasing
      nowadays. The majority of MGUS is being addressed to a hematologist for diagnosis
      or follow-up by their generalist practitioners. The management of MGUS consists
      of a clinical and biological surveillance as per published and validated
      international guidelines available for MGUS diagnosis and follow-up. MGUS thus
      may not necessarily need a specialized consultation and follow-up in a hematology
      ward, as we believe it could be performed by generalist practitioners. METHODS:
      We studied 190 patients addressed to our hematology department of Lille for
      diagnosis or follow-up of MGUS. RESULTS: Among the patients, 9.5% developed a
      malignant hemopathy (multiple myeloma or Waldenstrom macroglobulinemia). Among
      patients diagnosed with MGUS of IgG isotype and a monoclonal component <15 g/L,
      96.2% showed no pejorative outcome: these represent simple and routine prognostic
      factors that can be assessed at diagnosis in order to predict the risk of
      progression. Those patients could have easily been followed by their generalist
      practitioner from the diagnosis of MGUS. CONCLUSION: A specialist's consultation
      would still be recommended for patients with pejorative factors at diagnosis, or
      if a clinical or biological event that could suggest progression occurs during
      follow-up, or in case of MGUS with complication, in which cases patients would
      need a specialized management in a hematology department.

PMID- 25596922
TI  - Effects of different pretreatments on the performance of ceramic ultrafiltration
      membrane during the treatment of oil sands tailings pond recycle water: a pilot
      scale study.
AB  - Membrane filtration is an effective treatment method for oil sands tailings pond
      recycle water (RCW); however, membrane fouling and rapid decrease in permeate
      flux caused by colloids, organic matter, and bitumen residues present in the RCW
      hinder its successful application. This pilot-scale study investigated the impact
      of different pretreatment steps on the performance of a ceramic ultrafiltration
      (CUF) membrane used for the treatment of RCW. Two treatment trains were examined:
      treatment train 1 consisted of coagulant followed by a CUF system, while
      treatment train 2 included softening (MultifloTM system) and coagulant addition,
      followed by a CUF system. The results indicated that minimum pretreatment (train
      1) was required for almost complete solids removal. The addition of a softening
      step (train 2) provided an additional barrier to membrane fouling by reducing
      hardness-causing ions to negligible levels. More than 99% removal of turbidity
      and less than 20% removal of total organic carbon were achieved regardless of the
      treatment train used. Permeate fluxes normalized at 20  degrees C of 127-130
      L/m(2) h and 111-118 L/m(2) h, with permeate recoveries of 90-93% and 90-94% were
      observed for the treatment trains 1 and 2, respectively. It was also found that
      materials deposited onto the membrane surface had an impact on trans-membrane
      pressure and influenced the required frequencies of chemically enhanced
      backwashes (CEBs) and clean-in-place (CIP) procedures. The CIP performed was
      successful in removing fouling and scaling materials such that the CUF
      performance was restored to baseline levels. The results also demonstrated that
      due to their low turbidity and silt density index values, permeates produced in
      this pilot study were suitable for further treatment by high pressure membrane
      processes.

PMID- 25596923
TI  - Vitamin D promotes human extravillous trophoblast invasion in vitro.
AB  - INTRODUCTION: Incomplete human extravillous trophoblast (EVT) invasion of the
      decidua and maternal spiral arteries is characteristic of pre-eclampsia, a
      condition linked to low maternal vitamin D status. It is hypothesized that
      dysregulated vitamin D action in uteroplacental tissues disrupts EVT invasion
      leading to malplacentation. METHODS: This study assessed the effects of the
      active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3), and its
      precursor, 25-hydroxyvitamin D3 (25-D3), on primary human EVT isolated from first
      trimester pregnancies. Expression of EVT markers (cytokeratin-7, HLA-G), the
      vitamin D-activating enzyme (CYP27B1) and 1,25-D3 receptor (VDR) was assessed by
      immunocytochemistry. EVT responses following in vitro treatment with 1,25-D3 (0
      10 nM) or 25-D3 (0-100 nM) for 48-60 h were assessed using quantitative RT-PCR
      (qRT-PCR) analysis of key target genes. Effects on EVT invasion through
      Matrigel((r)) were quantified alongside zymographic analysis of secreted matrix
      metalloproteinases (MMPs). Effects on cell viability were assessed by measurement
      of MTT. RESULTS: EVT co-expressed mRNA and protein for CYP27B1 and VDR, and
      demonstrated induction of mRNA encoding vitamin D-responsive genes, 24
      hydroxylase (CYP24A1) and cathelicidin following 1,25-D3 treatment. EVT could
      respond to 1,25-D3 and 25-D3, both of which significantly increased EVT invasion,
      with maximal effect at 1 nM 1,25-D3 (1.9-fold; p < 0.01) and 100 nM 25-D3 (2.2
      fold; p < 0.05) respectively compared with untreated controls. This was
      accompanied by increased pro-MMP2 and pro-MMP9 secretion. The invasion was
      independent of cell viability, which remained unchanged. DISCUSSION: These data
      support a role for vitamin D in EVT invasion during human placentation and
      suggest that vitamin D-deficiency may contribute to impaired EVT invasion and pre
      eclampsia.

PMID- 25596925
TI  - Drinking well water and occupational exposure to Herbicides is associated with
      chronic kidney disease, in Padavi-Sripura, Sri Lanka.
AB  - BACKGROUND: The chronic kidney disease of unknown etiology (CKDu) among paddy
      farmers in was first reported in 1994 and has now become most important public
      health issue in dry zone of Sri Lanka. The objective was to identify risk factors
      associated with the epidemic in an area with high prevalence. METHODS: A case
      control study was carried out in Padavi-Sripura hospital in Trincomalee district.
      CKDu patients were defined using health ministry criteria. All confirmed cases (N
      = 125) fulfilling the entry criteria were recruited to the study. Control
      selection (N = 180) was done from people visiting the hospital for CKDu
      screening. Socio-demographic and data related to usage of applying pesticides and
      fertilizers were studied. Drinking water was also analyzed using ICP-MS and ELISA
      to determine the levels of metals and glyphosate. RESULTS: Majority of patients
      were farmers (N = 107, 85.6%) and were educated up to 'Ordinary Level' (N = 92,
      73.6%). We specifically analyzed for the effect modification of, farming by sex,
      which showed a significantly higher risk for male farmers with OR 4.69 (95% CI
      1.06-20.69) in comparison to their female counterparts. In the multivariable
      analysis the highest risk for CKDu was observed among participants who drank well
      water (OR 2.52, 95% CI 1.12-5.70) and had history of drinking water from an
      abandoned well (OR 5.43, 95% CI 2.88-10.26) and spray glyphosate (OR 5.12, 95% CI
      2.33-11.26) as a pesticide. Water analysis showed significantly higher amount of
      hardness, electrical conductivity and glyphosate levels in abandoned wells. In
      addition Ca, Mg, Ba, Sr, Fe, Ti, V and Sr were high in abandoned wells. Surface
      water from reservoirs in the endemic area also showed contamination with
      glyphosate but at a much lower level. Glyphosate was not seen in water samples in
      the Colombo district. CONCLUSION: The current study strongly favors the
      hypothesis that CKDu epidemic among farmers in dry zone of Sri Lanka is
      associated with, history of drinking water from a well that was abandoned. In
      addition, it is associated with spraying glyphosate and other pesticides in paddy
      fields. Farmers do not use personnel protective equipments and wears scanty
      clothing due to heat when spraying pesticides.

PMID- 25596926
TI  - Risk of suicide among female adolescents with eating disorders: a longitudinal
      population-based study.
AB  - PURPOSE: Suicide is a major cause of death among individuals with eating
      disorders. This study examined risk of suicide among females with eating
      disorders based on population-based military data. METHODS: Data on diagnoses of
      eating disorders from the pre-induction screening for psychopathology and
      diagnoses assigned during military service were merged with data on later suicide
      from the nationwide Israeli Death Registry. We identified 1,356 females with
      eating disorders and compared their risk of suicide to a population-based control
      group of females without eating disorders over a mean follow-up period of 8.5 +/-
      5.34 years. RESULTS: Females with eating disorders had a higher rate of suicide
      (0.22 %, n = 3) compared to females without eating disorders (0.03 %, n = 166).
      Having a moderate-severe eating disorder was associated with increased risk of
      suicide (RR = 12.50, 95 % CI = 3.86-38.09), whereas none of the females diagnosed
      as having a mild eating disorder died by suicide. CONCLUSIONS: Females with
      moderate-severe eating disorders are at risk of suicide and should be monitored
      for suicidal intent.

PMID- 25596924
TI  - A comparison of the predictive accuracy of three screening models for pulmonary
      arterial hypertension in systemic sclerosis.
AB  - INTRODUCTION: There is evidence that early screening for pulmonary arterial
      hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the
      predictive accuracy of two recently published screening algorithms (DETECT 2013
      and Australian Scleroderma Interest Group (ASIG) 2012) for SSc-associated PAH
      (SSc-PAH) with the commonly used European Society of Cardiology/European
      Respiratory Society (ESC/ERS 2009) guidelines. METHODS: We included 73
      consecutive SSc patients with suspected PAH undergoing right heart
      catheterization (RHC). The three screening models were applied to each patient.
      For each model, contingency table analysis was used to determine sensitivity,
      specificity, and positive (PPV) and negative (NPV) predictive values for PAH.
      These properties were also evaluated in an 'alternate scenario analysis' in which
      the prevalence of PAH was set at 10%. RESULTS: RHC revealed PAH in 27 (36.9%)
      patients. DETECT and ASIG algorithms performed equally in predicting PAH with
      sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and
      NPV of only 91%, missing one case of PAH; these guidelines could not be applied
      to three patients who had absent tricuspid regurgitant (TR) jet. The ASIG
      algorithm had the highest specificity (54.5%). With PAH prevalence set at 10%,
      the NPV of the models was unchanged, but the PPV dropped to less than 20%.
      CONCLUSIONS: In this cohort, the DETECT and ASIG algorithms out-perform the
      ESC/ERS guidelines, detecting all patients with PAH. The ESC/ERS guidelines have
      limitations in the absence of a TR jet. Ultimately, the choice of SSc-PAH
      screening algorithm will also depend on cost and ease of application.

PMID- 25596927
TI  - Responses of rose RhACS1 and RhACS2 promoters to abiotic stresses in transgenic
      Arabidopsis thaliana.
AB  - KEY MESSAGE: Promoter activities of RhACS1 and RhACS2 , two rose genes involved
      in ethylene biosynthesis, are highly sensitive to various abiotic stresses in an
      organ-specific manner. Our previous studies indicated that two rose (Rosa
      hybrida) 1-aminocyclopropane-1-carboxylic acid synthase genes, RhACS1 and RhACS2,
      play a role in dehydration-induced ethylene production and inhibition of cell
      expansion in rose petals. Here, both RhACS1 and RhACS2 promoters were analyzed
      using histochemical staining and glucuronidase synthase (GUS) gene reporter
      activity assays following their introduction into transgenic Arabidopsis thaliana
      plants. It was found that the promoter activities of both genes were strong
      throughout the course of development from young seedlings to mature flowering
      plants in various organs, including hypocotyls, cotyledons, leaves, roots and
      lateral roots. RhACS1 promoter activity was induced by drought in both rosette
      leaves and roots of transgenic A. thaliana lines, but was reduced following a re
      hydration treatment. In contrast, RhACS2 promoter activity was decreased by
      drought in rosette leaves, while its response pattern was similar to that of
      RhACS1 in roots. A mannitol treatment induced the activity of both the RhACS1 and
      RhACS2 promoters, indicating that both genes are also regulated by osmotic
      stress. In addition, RhACS2 appeared to be abscisic acid (ABA)-inducible, while
      RhACS1 was less sensitive to ABA. Finally, four truncated sequences of the RhACS1
      promoter were generated and GUS activity assays demonstrated that deleting a 327
      bp region between bp 862 and -535 resulted in a substantial decrease of the
      promoter activity. Taken together, our results suggest that the RhACS1 and RhACS2
      promoters respond to abiotic stresses in a developmentally regulated and
      spatially specific manner.

PMID- 25596928
TI  - MiR-22-silenced cyclin A expression in colon and liver cancer cells is regulated
      by bile acid receptor.
AB  - Because of the significant tumor-suppressive role of microRNA-22 (miR-22), the
      current study was designed to understand the regulation of miR-22 and to identify
      additional downstream miR-22 targets in liver and colon cells. The data showed
      that miR-22 was transcriptionally regulated by bile acid receptor farnesoid X
      receptor (FXR) through direct binding to an invert repeat 1 motif located at 
      1012 to -1025 bp upstream from miR-22. Among the studied primary and secondary
      bile acids, chenodeoxycholic acid, which has the highest binding affinity to FXR,
      induced miR-22 level in both Huh7 liver and HCT116 colon cells in a dose- and
      time-dependent manner. In addition, cyclin A2 (CCNA2) was identified as a miR-22
      novel target in liver and colon cancer cells. The sequence of miR-22, which is
      conserved in mice, rats, humans, and other mammalians, aligns with the sequence
      of 3'-UTR of CCNA2. Chenodeoxycholic acid treatment and miR-22 mimics reduced
      CCNA2 protein and increased the number of G0/G1 Huh7 and HCT116 cells. In FXR KO
      mice, reduction of miR-22 was accompanied by elevated hepatic and ileal CCNA2
      protein, as well as an increased number of hepatic and colonic Ki-67-positive
      cells. In humans, the expression levels of miR-22 and CCNA2 are inversely
      correlated in liver and colon cancers. Taken together, our data showed that bile
      acid-activated FXR stimulates miR-22-silenced CCNA2, a novel pathway for FXR to
      exert its protective effect in the gastrointestinal tract. 

PMID- 25596929
TI  - An Efficacy Trial of an Intervention Program for Children Exposed to Intimate
      Partner Violence.
AB  - Children exposed to intimate partner violence (IPV) are at high risk for
      adjustment problems, especially internalizing disorders. Few evidence-based
      interventions are available to address internalizing behavior problems in this
      population. An efficacy trial compared outcomes for 4-6 year old children
      randomly assigned to a program designed to address the effects of exposure to IPV
      with those allocated to a waitlist comparison condition. Mothers (N = 120) and
      children from the United States and Canada were assessed at baseline, 5 weeks
      later (post-intervention) and at 8-month follow-up. The evaluation compared rates
      of change over time for child internalizing problems. Results were analyzed using
      both intent-to-treat (ITT) and per-protocol (PP) approaches. ITT analyses
      indicated the program reduced internalizing problems for girls at follow-up. PP
      analyses indicated the program reduced internalizing problems for both boys and
      girls at post-intervention. In this study, child internalizing problems were
      significantly reduced through an intervention for the mother and the child.

PMID- 25596930
TI  - Patients with chronic hepatitis C without advanced fibrosis and hepatocellular
      carcinoma: a retrospective clinical-pathological study.
AB  - BACKGROUND: There are very few studies on the incidence and risk factors of
      hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) in the absence of
      advanced fibrosis. Our objective was to identify the clinical-pathological
      features of these patients. METHODS: We retrospectively reviewed 162 patients
      admitted to our hospital for HCV-related HCC between 2000 and 2010. Patients with
      hepatitis of other aetiologies, human immunodeficiency virus co-infection, or
      treated with interferon were excluded. We compared demographic, laboratory,
      clinical and outcome parameters of patients with and without advanced fibrosis.
      RESULTS: 137 patients had advanced fibrosis (85%). Median age was higher in the
      advanced fibrosis vs. the non-advanced fibrosis group (62 vs. 65 years,
      respectively; p = 0.025). Steatosis was significantly more frequent in patients
      with advanced fibrosis compared to those without advanced fibrosis (43% vs. 20%,
      respectively; p = 0.032). Independent predictors associated to the occurrence of
      HCC in patients without advanced fibrosis were hepatitis B core antigen (odds
      ratio: 3.86; p = 0.044) and duration of hepatitis C infection (odds ratio: 1.21;
      p = 0.003). CONCLUSIONS: Risk factors such as steatosis or diabetes were not
      frequent in patients without advanced fibrosis. Further studies are needed to
      evaluate the role of occult hepatitis B and the duration of hepatitis infection
      in patients with HCC and chronic hepatitis C without advanced fibrosis.

PMID- 25596931
TI  - Endoscopic ultrasound-guided fine needle tissue acquisition biopsy samples do not
      allow a reliable proliferation assessment of gastrointestinal stromal tumours.
AB  - BACKGROUND: Current prognostication of gastrointestinal stromal tumours is
      validated on/applies to resected tumours, mainly because surgery is recommended
      whenever possible. However, pre-treatment prognostication is increasingly
      warranted, considering the follow-up strategy recently admitted for expectedly
      low-risk tumours and the possible distinctive molecular features/spontaneous
      regression of some small cases. AIMS: To investigate whether endoscopic
      ultrasound-guided fine-needle tissue acquisition-biopsies reflect prognosticators
      of resected gastrointestinal stromal tumours, for possibly developing reliable
      pre-treatment prognostic criteria. METHODS: The applicability/reliability of
      mitotic index/5mm(2) and MIB1 proliferative index/1000 cells were tested in 35
      endoscopic ultrasound-guided fine-needle tissue acquisition-biopsies diagnosed as
      gastrointestinal stromal tumour, subsequently resected without intervening
      therapy, consecutively collected in thirty months. Size and mitotic/proliferative
      indexes were compared with resection specimens. The feasibility of bioptic
      genotyping was also tested. RESULTS: 35 patients were studied (45.7% males; mean
      age 61.6 years, range 26-83 years). Mitotic/proliferative indexes were
      determinable in 68.6%/88.6% of biopsies, respectively; they were nevertheless
      underestimated, as happened with endoscopic ultrasound-determined tumour size.
      Bioptic genotyping revealed reliable. CONCLUSIONS: Endoscopic ultrasound-guided
      fine-needle tissue acquisition does not reliably reflect gastrointestinal stromal
      tumours' proliferation and size. Alternative parameters should be validated for a
      pre-surgical prognostic classification. Considering the emerging potentially
      prognostic genetic markers in gastrointestinal stromal tumours, the reliability
      of bioptic genotyping is a promising result.

PMID- 25596932
TI  - Effects of two fast-setting calcium-silicate cements on cell viability and
      angiogenic factor release in human pulp-derived cells.
AB  - Mineral trioxide aggregate (MTA) is considered a pulp-capping agent of choice,
      but has the drawback of a long setting time. This study aimed to assess two
      different types of calcium-silicate cements as pulp-capping agents, by
      investigating their in vitro cytotoxicity and angiogenic effects in human pulp
      cells. ProRoot MTA, Endocem Zr, and Retro MTA were prepared as set or freshly
      mixed pellets. Human pulp-derived cells were grown in direct contact with these
      three cements, Dycal, or no cement, for 7 days. Initial cell attachment,
      viability, calcium release, and the levels of vascular endothelial growth factor
      (VEGF), angiogenin, and basic fibroblast growth factor (FGF-2) were evaluated
      statistically using a linear mixed model (P < 0.05). The biocompatibility of
      Retro MTA was similar to those of the control and ProRoot MTA. Endocem Zr groups
      showed fewer and more rounded cells after a 3-day culture; however, the initial
      cytotoxicity appeared transient. All test materials showed significant increases
      in calcium concentration compared with the control group (P < 0.05). VEGF and
      angiogenin levels in ProRoot MTA and Retro MTA groups were significantly higher
      than those in the Endocem Zr group (P < 0.05). FGF-2 levels were not
      significantly different between groups (P > 0.05). We demonstrate that Retro MTA,
      which has a short setting time, has similar biocompatibility and angiogenic
      effects on human pulp cells, and can therefore potentially be as effective in
      pulp capping as ProRoot MTA. Endocem Zr showed intermittent cytotoxicity and
      elicited lower levels of VEGF and angiogenin expression.

PMID- 25596933
TI  - Membrane water permeability of maize root cells under two levels of oxidative
      stress.
AB  - Changes in the total water permeability of two cell membranes (plasmalemma and
      tonoplast), estimated by the effective diffusion coefficient of water (D ef),
      were controlled using the NMR method. The time dynamics of D ef in maize (Zea
      mays L.) root cells was studied in response to (i) root excision from seedling
      and the following 6-h incubation in the growth medium (wound stress) and (ii) the
      superposition of wound stress plus paraquat, which induces the excess of reactive
      oxygen species (ROS). The dynamics of lipid peroxidation, oxygen consumption, and
      heat production was studied to estimate general levels of oxidative stress in two
      variants of experiments. Under wound stress (the weak oxidative stress), the
      reversible by dithiothreitol increase in cell membrane water permeability was
      observed. The applicability of mercury test to aquaporin activity in our
      experiments was verified. The results of wound stress effect, obtained using this
      test, are discussed in terms of oxidative upregulation of aquaporin activity by
      ROS. The increase of oxidative stress in cells (wound-paraquat stress), contrary
      to wound stress, was accompanied by downregulation of membrane water
      permeability. In this case, ROS is supposed to affect the aquaporins not directly
      but via such processes as peroxidation of lipids, inactivation of some
      intracellular proteins, and relocalization of aquaporins in cells. 

PMID- 25596934
TI  - Laser-assisted lipolysis for arm contouring in Teimourian grades I and II: a
      prospective study of 45 patients.
AB  - Upper arm deformities secondary to weight loss or senile elastosis have led to an
      increased demand for aesthetic contouring procedures. We conducted this study to
      objectively assess if, in Teimourian low-grade upper arm remodelling, one session
      of laser-assisted lypolisis (LAL) could result in full patient satisfaction.
      Between 2011 and 2013, 45 patients were treated for unsightly fat arm Teimourian
      grade I (15 patients), grade IIa (15 patients) and grade IIb (15 patients) with
      one session of LAL. The laser used in this study was a 1470-nm diode laser (Alma
      Lasers, Cesarea, Israel) with the following parameters: continuous mode, 15 W
      power and transmission through a 600-MUm optical fibre. Previous mathematical
      modelling suggested that 0.1 kJ was required in order to destroy 1 ml of fat.
      Treatment parameters and adverse effects were recorded.The arm circumference and
      skin pinch measurements were assessed pre and postoperatively. Patients were
      asked to file a satisfaction questionnaire. Pain during the anaesthesia and
      discomfort after the procedure were minimal. Complications included prolonged
      oedema in 11 patients. The average arm circumference decreased by 4.9 +/- 0.4 cm
      in the right arm (p < 0.01) and 4.7 +/- 0.5 cm in the left arm (p < 0.01) in
      grade I patients, 5.5 +/- 0.6 cm in the right arm (p < 0.01) and 5.2 +/- 0.5 cm
      in the left arm (p < 0.01) in grade IIa patients and 5.4 +/- 0.5 cm in the right
      arm (p < 0.01) and 5.3 +/- 0.5 cm in the left arm (p < 0.01) in grade IIB
      patients. The skin tightening effect was confirmed by the reduction of the skin
      calliper measurements in all three groups. Overall mean opinion of treatment was
      high for both patients and investigators. Of the 45 patients, all but one would
      recommend this treatment. A single session of LAL in upper arm remodelling for
      Teimourian grades I to IIb is a safe and reproducible technique. The procedure
      allows reduction in the amount of adipose deposits while providing full skin
      tightening.

PMID- 25596935
TI  - Effect of low-level laser therapy on bone repair: a randomized controlled
      experimental study.
AB  - The aim of this study was to investigate the effect of low-level laser therapy
      (LLLT) on bone repair in femoral fractures. Sixty adult Wistar rats were randomly
      assigned into one of two groups: group A (ostectomy + LLLT) or group B (ostectomy
      + sham laser). An experimental model of complete bone fracture was surgically
      created by removing a 2-mm fragment from the middle third of the femoral shaft.
      Data were analyzed on days 8, 13, and 18 after the fracture (subgroups 1, 2, and
      3). Samples were assessed for changes in inflammatory infiltration; trabecular
      bone matrix, periosteal, and new bone formations; and changes in the expression
      of particular osteogenic-related proteins (osteocalcin, osteopontin, and
      osteonectin). Microscopic analysis revealed a significant decrease in
      inflammatory infiltration, intense trabecular bone matrix and periosteal
      formation, and an increase in newly formed bone after laser irradiation. We also
      found an increase in the expression of bone matrix proteins with LLLT, with a
      significant difference measured for osteocalcin in the LLLT group at day 8 (p =
      0.007). We show that LLLT plays an important role in augmenting bone tissue
      formation, which is relevant to fracture healing. LLLT may therefore be indicated
      as an adjunct therapeutic tool in clinical practice for the treatment or recovery
      of nonunion injuries.

PMID- 25596936
TI  - Male biased gene flow in banana pseudostem weevil (Odoiporus longicollis Oliver)
      as revealed by analysis of the COI-tRNA(Leu) COII region.
AB  - The genetic diversity amongst thirty weevils representing six Indian populations
      of banana pseudostem weevil, i.e., Odoiporus longicollis (Oliver) was estimated
      by sequence analysis of the partial COI-tRNA(Leu)-COII region. The sequences
      exhibited AT bias typical of insect mitochondrial DNA which was highest in the
      first codon position of COI and in the third codon position of COII. There was no
      phylogeographic distribution of the populations. The Fu and Li's D and F tests
      were non-significant for this mitochondrial region. No Wolbachia infection was
      detected in any of the populations. The genetic differentiation amongst the
      populations was highly significant (p < 0.001; chi2 = 123.333; df = 75),
      suggesting restricted gene flow between the populations. This result did not
      correlate with that obtained with nuclear rDNA markers, i.e., ITS1 and ITS2,
      suggesting a male biased gene flow between the populations.

PMID- 25596937
TI  - Incidental finding of GIST during obesity surgery.
AB  - BACKGROUND: The purpose of this study was to review the incidence of incidental
      gastrointestinal stromal tumors (GISTs) in a cohort of morbidly obese patients
      undergoing laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass
      (RYGB), analyzing surgery indication, morbidity, and follow-up data. METHODS: All
      cases with incidental GISTs found were reviewed. RESULTS: Two thousand six
      hundred three patients underwent obesity surgery founding a gastric GIST in eight
      patients (incidence 0.31 %). Mean tumor size was 7.65 mm (range 2.5-13 mm) with
      the majority of the lesions located in the fundus of the stomach. All lesions had
      negative resection margins. At a mean follow-up of 30 months, all patients were
      disease-free. CONCLUSION: The long-term disease-free survival of 100 % in our
      study establishes laparoscopic wedge resection during RYGB and LSG as safe and
      effective in treating incidental gastric GISTs <2 cm.

PMID- 25596938
TI  - High-Dose Vitamin D Supplementation is Necessary After Bariatric Surgery: A
      Prospective 2-Year Follow-up Study.
AB  - BACKGROUND: We assessed the need of vitamin D supplementation to achieve normal
      25-hydroxyvitamin D (25[OH]D) levels after bariatric surgery and whether there
      were differences between laparoscopy sleeve gastrectomy (LSG) and laparoscopic
      Roux-en-Y gastric bypass (LRYGB). METHODS: A total of 164 morbid obese patients
      undergoing bariatric surgery from January 2008 to June 2011 were followed for 2
      years. Serum levels of 25(OH)D and intact parathyroid hormone (iPTH) were
      measured preoperatively and at 3, 6, 9, 12, 18, and 24 months after operation.
      All patients received 400 IU/day of 25(OH)D. Patients received additional
      supplementation with 16,000 IU of vitamin D3 (calcifediol) every 2 weeks if
      25(OH)D serum levels were < 30 ng/mL (intervention group). RESULTS: Ninety-six
      (58.5 %) patients underwent LSG and 68 (41.5 %) LRYGB. A total of 106 (64.6 %)
      patients received calcifediol supplementation (62 in the LSG group and 44 in the
      LRYGB group). Normal 25(OH)D levels at 24 months were recorded in 69 % of
      patients in the intervention group and in 48.3 % in the non-intervention group.
      At 24 months, mean 25(OH)D levels in the non-intervention group were
      significantly lower among LRYGB patients than among LSG patients (P = 0.009). In
      the intervention group, normal 25(OH)D levels were achieved in 60 % of patients
      treated with LSG and in 22.2 % of those treated with LRYGB. Secondary
      hyperparathyroidism was presented in 49 (29.9 %) patients preoperatively but
      without significant differences in iPTH levels between the two surgical
      procedures. CONCLUSION: Patients undergoing bariatric surgery should receive high
      dose vitamin D supplementation independently of the surgical technique.

PMID- 25596939
TI  - Minimizing Hemorrhagic Complications in Laparoscopic Sleeve Gastrectomy--a
      Randomized Controlled Trial.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained worldwide popularity
      in recent years. Hemorrhagic complications (HC) are usually the result of stapler
      line bleeding and are probably underreported. The previous incidence of HC in our
      department including minor bleeding and late hematomas was 15.0 %. The objective
      of this study is to assess the impact of stapler line reinforcement (SLR) and
      intraoperative blood pressure control on HC after LSG. METHODS: Between February
      2013 and March 2014, patients who were admitted to our department for LSG were
      randomly assigned to one of three arms: stapler line application of biologic glue
      -EvicelTM (E), over suture of the stapler line (S) or control (C). Surgical
      technique in all arms included blood pressure elevation to 140 mmHg before
      termination of the procedure. Data is presented as mean +/- SD or median (IQR 25
      75). RESULTS: One hundred sixty-five patients were randomized: 49 to E, 49 to S,
      and 67 to C. There were no demographic differences between arms. Operative time
      was significantly longer in S than in E and C arms (74 +/- 21 vs. 64 +/- 23 and
      54 +/- 19 min, respectively). ?Hb was significantly lower in the S group. Packed
      cells were used in two from E and one from C arms. Late infected hematoma
      occurred in three (1.8 %) patients: one from E and two from C arms. Leak rate was
      1.2 %: one from S and one from C arms. LOS was the same. No patients were re
      operated due to bleeding. CONCLUSIONS: In this randomized trial, routine
      elevation of systolic blood pressure to 140 mmHg and over suture of the staple
      line in LSG minimized HC, with reasonable prolongation of the procedure.

PMID- 25596941
TI  - Open ankle fractures: who gets them and why?
AB  - Open ankle fractures present a significant clinical challenge. The management and
      outcome of these injuries has been extensively reported, but there have been no
      reports of the epidemiology and how this has changed over time. We report 178
      adult patients with open ankle fractures presenting to our unit over a twenty
      three year period. The study centre is the only hospital receiving adult
      orthopaedic trauma in the region and has a defined population. The incidence of
      open ankle fractures was 1.5/10(5)/year, representing 1.5 % of all ankle
      fractures. The mean age was 55 years (range 16-96), with the highest incidence
      occurring in women over the age of 90. The most common mechanism was a simple
      fall with only 26 % of cases due to a motor vehicle collision (MVC). 82 % of
      cases were isolated injuries. Social deprivation had no significant influence on
      the incidence, but there was a difference in the mechanism with the majority of
      injuries in the most deprived quintile caused by MVCs and significantly fewer due
      to simple falls (p = 0.047). Over the twenty-three years, there was a significant
      increase in the mean age from 44 to 64 years (p = 0.03). The overall incidence
      remained constant over the two decades. In common with many traumatic injuries,
      open ankle fractures are increasingly low-energy insufficiency fractures
      affecting elderly patients, particularly older women. This has implications for
      service planning and training as well as the surgical intervention in these
      patients. 

PMID- 25596940
TI  - Left ventricular global longitudinal systolic strain predicts adverse remodeling
      and subsequent cardiac events in patients with acute myocardial infarction
      treated with primary percutaneous coronary intervention.
AB  - To determine whether left ventricular (LV) global longitudinal strain (GLS)
      predicts adverse LV remodeling and cardiac events. In a prospective cohort study
      of patients with acute myocardial infarction (AMI) undergoing primary
      percutaneous coronary intervention (PCI), we recorded clinical data and GLS,
      global circumferential strain and radial strain using two-dimensional speckle
      tracking echocardiography of the left ventricle. At 6-month and 3-year follow
      ups, patients were grouped by presence or absence of adverse LV remodeling. We
      used logistic regression to identify factors associated with adverse LV
      remodeling and a Cox model to determine the relationships between these factors
      and cardiac events. Of 97 patients (mean age 56 +/- 12 years; 76 men), 38 showed
      LV remodeling. Diabetes mellitus [odds ratio (OR) 1.95% confidence interval (CI)
      1.2-4.8, p = 0.05], peak troponin I (OR 1.2, 95% CI 1.1-1.3, p = 0.004), and GLS
      (OR 1.6, 95% CI 1.3-2.3, p = 0.009) independently predicted LV remodeling. During
      follow-up (22.8 +/- 12.3 months), 20 patients suffered adverse events, which were
      independently predicted by GLS alone (OR 4.9, 95% CI 1.7-13.9, p = 0.002).
      Optimal GLS cutoffs for predicting adverse LV remodeling and cardiac events were
      >-12.46% [area under receiver operating-characteristic curve (AUC) 0.88, 95% CI
      0.79-0.96, p < 0.001] and >-9.27% (AUC 0.86, 95% CI 0.64-0.98, p < 0.001),
      respectively. GLS measured immediately after primary PCI is an excellent
      predictor of adverse LV remodeling and cardiac events in patients with AMI.

PMID- 25596942
TI  - DHA inhibited AGEs-induced retinal microglia activation via suppression of the
      PPARgamma/NFkappaB pathway and reduction of signal transducers in the AGEs/RAGE
      axis recruitment into lipid rafts.
AB  - Recent studies revealed that dietary intake of docosahexaenoic acid (DHA)
      prevented diabetic retinopathy (DR), but the underlying mechanism was not fully
      understood. Retinal microglia are a specialized population of macrophages in
      retina. Considerable evidence has shown that microglia activation may trigger
      neuronal death and vascular dysfunction in DR. The aim of this study was to
      investigate the effects of DHA on advanced glycation end products (AGEs)-induced
      microglia activation using an in vitro microglia culture system, and concurrently
      to explore the mediating mechanisms. DHA inhibited AGEs-induced microglia
      activation and tumor necrosis factor alpha (TNFalpha) secretion. These effects of
      DHA were directly linked with suppression of nuclear factor-kappa B (NFkappaB)
      activity, as evident by the reduction of p-IkappaBalpha expression, p-NFkappaB
      p65 nucleus translocation, NFkappaB DNA binding activity, and the regulation of
      gene transcription (TNFalpha, IL-1beta, ICAM-1, and RAGE mRNA). Furthermore, DHA
      significantly increased phosphorylation of peroxisome proliferator-activated
      receptor-gamma (PPARgamma), and combined with PPARgamma stealth RNAi
      oligonucleotide, we confirmed that DHA inhibition of AGEs-induced microglia
      activation was partially through the PPARgamma/NFkappaB pathway. Moreover,
      although AGEs incubation dramatically elevated expression of the cell surface
      receptor for AGEs (RAGE), DHA significantly inhibited RAGE and Src recruitment
      into lipid rafts. The AGEs-RAGE axis downstream signal transducers increased
      mitogen-activated protein kinase (p38 and JNK) phosphorylation. Taken together,
      DHA might inhibit AGEs-induced microglia activation via suppression of the
      PPARgamma/NFkappaB pathway, and reduction of RAGE and AGEs/RAGE transducer
      recruitment into lipid rafts. These results provide a novel potential mechanism
      for the anti-inflammatory effects of DHA in DR prevention. 

PMID- 25596944
TI  - An abuse of risk assessment: how regulatory agencies improperly adopted LNT for
      cancer risk assessment.
AB  - The Genetics Panel of the National Academy of Sciences' Committee on Biological
      Effects of Atomic Radiation (BEAR) recommended the adoption of the linear dose
      response model in 1956, abandoning the threshold dose-response for genetic risk
      assessments. This recommendation was quickly generalized to include somatic cells
      for cancer risk assessment and later was instrumental in the adoption of
      linearity for carcinogen risk assessment by the Environmental Protection Agency.
      The Genetics Panel failed to provide any scientific assessment to support this
      recommendation and refused to do so when later challenged by other leading
      scientists. Thus, the linearity model used in cancer risk assessment was based on
      ideology rather than science and originated with the recommendation of the NAS
      BEAR Committee Genetics Panel. Historical documentation in support of these
      conclusions is provided in the transcripts of the Panel meetings and in
      previously unexamined correspondence among Panel members. 

PMID- 25596943
TI  - Delineating the factors and cellular mechanisms involved in the survival of
      cerebellar granule neurons.
AB  - Cerebellar granule neurons (CGNs) constitute the most abundant neuronal
      population in the mammalian brain. Their postnatal generation and the feasibility
      to induce their apoptotic death in vitro make them an excellent model to study
      the effect of several neurotransmitters and neurotrophins. Here, we first review
      which factors are involved in the generation and proliferation of CGNs in the
      external granule layer (EGL) and in the regulation of their differentiation and
      migration to internal granule layer (IGL). Special attention was given to the
      role of several neurotrophins and the NMDA subtype of glutamate receptor. Then,
      using the paradigm of potassium deprivation in cultured CGNs, we address several
      extracellular factors that promote the survival of CGNs, with particular emphasis
      on the cellular mechanisms. The role of specific protein kinases leading to the
      regulation of transcription factors and recent data involving the small G protein
      family is also discussed. Finally, the participation of some members of Bcl-2
      family and the inhibition of mitochondria-related apoptotic pathway is also
      considered. Altogether, these studies evidence that CGNs are a key model to
      understand the development and the survival of neuronal populations. 

PMID- 25596945
TI  - Effect of lidocaine on swine lingual and pulmonary arteries.
AB  - PURPOSE: Lidocaine has a biphasic action on smooth muscle of peripheral blood
      vessels, with vasoconstriction at low concentrations and vasodilation at higher
      concentrations. Many in vivo studies have demonstrated the effects of lidocaine
      on aortic or coronary arteries in several animals, but there are few reports
      about the effect on peripheral vessels. This study was designed to investigate
      the direct effects of lidocaine on peripheral vessels, namely swine lingual and
      pulmonary arterial rings. METHODS: Swine lingual artery and pulmonary artery
      segments, about 2-3 mm in diameter, were cut into 3-mm-long rings, and the lumen
      surface was gently rubbed to remove the endothelium. Isometric tension was
      measured using a displacement transducer and recorded. After a stable
      constriction was developed with 5 uM noradrenaline, 5 uM noradrenaline containing
      lidocaine (0.5, 1.0, 10, 20, 50 or 100 ug/ml) was perfused for 5 min, and then
      all drug perfusion was stopped. The strength of any isometric tension during an
      experiment was normalized to the strength of the isometric tension immediately
      before lidocaine perfusion, and expressed as a percentage. RESULTS: Lidocaine
      elicited a concentration-dependent biphasic response of lingual and pulmonary
      arterial rings. The lidocaine concentration at 1 ug/ml caused mild contraction.
      Dilation occurred at 10 ug/ml and increased with increasing dose. CONCLUSIONS:
      Lidocaine-induced vasoconstriction of swine lingual and pulmonary smooth muscle
      may occur at low concentration when lidocaine is infiltrated into the oral
      submucosa or administered intravenously for the treatment of ventricular
      arrhythmia.

PMID- 25596946
TI  - A comparison of midazolam and dexmedetomidine for the recovery of serotonin
      syndrome in rats.
AB  - Serotonin syndrome is a drug-related toxicity caused by excess serotonin within
      the central nervous system. We recently encountered a case of serotonin syndrome
      that developed in the early postoperative period that was successfully treated
      with intravenous dexmedetomidine. Although the prescriptive literature has
      commonly recommended sedation with benzodiazepines for controlling agitation in
      serotonin syndrome, the effectiveness of dexmedetomidine has also been reported
      in several clinical conditions. In the present study, we conducted a reverse
      translational experiment to compare the efficacy of dexmedetomidine and
      midazolam, at equi-sedative doses, on serotonergic toxicity-like responses in
      rats. Animals were subcutaneously injected with 0.75 mg/kg 8-OH-DPAT, a full 5
      HT1A agonist. 8-OH-DPAT-treated rats showed serotonin syndrome-like behaviors
      (low body posture, forepaw treading), hyperlocomotion, and decreased body
      temperature, which were completely inhibited by pretreatment with WAY 100635, a
      selective 5-HT1A antagonist (n = 8). Intramuscular injection of midazolam (1.0
      mg/kg) or dexmedetomidine (0.01 mg/kg), which comparably induced observable signs
      of sedation, was tested in the present study. Concomitant treatment with
      midazolam significantly attenuated the hyperlocomotion, but failed to affect
      traditional serotonin syndrome behaviors and body temperature in 8-OH-DPAT
      treated rats (n = 8). On the other hand, concomitant treatment with
      dexmedetomidine significantly attenuated all of these parameters (n = 8). The
      present case and related reverse translational experiment demonstrate that
      dexmedetomidine may be more beneficial for the treatment of serotonin syndrome
      compared to the current recommended treatment with benzodiazepines. 

PMID- 25596947
TI  - Differential expression and DNA methylation of angiotensin type 1A receptors in
      vascular tissues during genetic hypertension development.
AB  - Angiotensin type 1a receptor (AT1aR) is thought to play an important role in the
      development of hypertension. However, it is unknown how the AT1aR expression in
      vascular tissue is changed during the development of hypertension or if the
      degree of methylation in the AT1aR promoter correlates with the expression of
      AT1aR. To address these questions, we measured AT1aR mRNA, protein expression,
      and methylation status of the AT1aR promoter in the aorta and mesenteric artery
      of male spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY)
      rats acting as controls at pre-hypertensive (4 weeks), evolving (10 weeks), and
      established (20 weeks) stages of hypertension. The expression of the AT1aR mRNA
      and protein was not different between the SHRs and WKY rats at 4 weeks. However,
      they were significantly greater in SHRs than in WKY rats at 20 weeks. Bisulfite
      sequencing revealed that the AT1aR promoter from the aorta and mesenteric artery
      of the SHRs was progressively hypo-methylated with age as compared with their WKY
      rat counterparts. These results suggest that the heightened AT1aR expression in
      SHRs is related to the AT1aR promoter hypo-methylation, which might be a
      consequence of the increased blood pressure and may be important in the
      maintenance of high blood pressure. 

PMID- 25596948
TI  - Quercetin inhibits proliferation and invasion acts by up-regulating miR-146a in
      human breast cancer cells.
AB  - Breast cancer is the most common female malignancies in the world which seriously
      impacts the female health. In recent years, various studies have been reported to
      determine the relevance of miRNAs to human cancer. One of these miRNAs, miR-146a
      has been down-regulated in multiple human cancer types, but up-regulation showed
      inducing apoptosis. To determine the role of quercetin treated on breast cancer,
      we investigated the effect of quercetin on cell proliferation in human breast
      cancer cell lines MCF-7 and MDA-MB-231 with/without transfection of miR-146a
      mimic or anti-miR-146a. Furthermore, the expressions of bax and cleaved-caspase
      3, mainly were increased in control and overexpression miR-146a groups, however,
      the expression of EGFR was inverse. All the results demonstrated that quercetin
      exhibited excellent effect on inhibiting cell proliferation in human breast
      cancer cells, which was performed by up-regulating miR-146a expression, then via
      inducing apoptosis through caspase-3 activation and mitochondrial-dependent
      pathways, and inhibiting invasion through down-regulating the expression of EGFR.

PMID- 25596949
TI  - Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage
      explant model of osteoarthritis.
AB  - OBJECTIVE: This study aimed to assess the chondroprotective potential of
      atorvastatin in rat's cartilage explant culture model of osteoarthritis,
      stimulated by interleukin-1beta (IL-1beta). MATERIALS AND METHODS: The cartilage
      explants were treated with 20 ng/ml IL-1beta alone or with 20 ng/ml IL-1beta +
      various concentration of atorvastatin (1, 3, or 10 uM dissolved in DMSO) and
      incubated at 37  degrees C for 24 h. Also, control (0.25% DMSO), stimulated (20
      ng IL-1beta) and treatment (atorvastatin 10 uM) cartilage explants were incubated
      without and with 1400W (10 uM). After 24 h of incubation, TNF-alpha, PGE2, MMP
      13, TIMP-1, NO, and superoxide anion formation (O2(-)) concomitant with
      glycosaminoglycans (GAGs) were estimated in the medium. RESULTS: Atorvastatin
      inhibited IL-1beta-induced GAGs release, TNF-alpha, MMP-13, and O2(-) with no
      effect on TIMP-1 and NO. In addition, the source of NO in normal and atorvastatin
      treated cartilage was eNOS, while for IL-1beta-stimulated cartilage it was iNOS.
      The cartilage degradation was associated with the combined effects of increased
      NO and O2 (-) rather than only NO. CONCLUSION: The present study suggests that
      atorvastatin has the ability to protect cartilage degradation following IL-1beta
      stimulated cartilage in in vitro OA model and supports additional therapeutic
      application of atorvastatin in OA.

PMID- 25596950
TI  - A model of skin inflammation in humans leads to a rapid and reproducible increase
      in the interferon response signature: a potential translational model for drug
      development.
AB  - OBJECTIVES: To investigate Toll-like receptor activation in human skin using tape
      stripping and imiquimod cream challenges in healthy volunteers. SUBJECTS,
      TREATMENT AND METHODS: Seventeen male Caucasian subjects underwent a baseline
      biopsy on their lower back prior to two tape stripping procedures 7 days apart.
      Subjects were then treated with 5% imiquimod for 2 and 4 days on separate sites
      in the same area. Further biopsies were taken 22-24 h after each challenge and
      mRNA and microRNA extracted and expression values analysed using robust
      statistical and pathway analysis methods. RESULTS: Fifteen of the 17 subjects
      completed the study according to protocol. No adverse events were associated with
      the procedures. A significant change (p < 0.05, fold change >1.5 or <-1.5) in
      mRNA expression of 7,996 genes was evident in biopsies taken at both time points
      post tape stripping, compared to baseline biopsy expression values. The induction
      of mRNAs involved in various pathways including adhesion and migration was
      evident. mRNA markers representing inflammatory cells [e.g., CD14, CD3E (p <
      0.0001)] and mRNAs encoding genes regulated by type 1 interferon (IFN) [e.g.,
      MX1, OAS1and CXCL10 (p < 0.0001)] were significantly up-regulated. IFNalpha and
      CXCL10 proteins were detectable in exudates released 1 and 4 h post tape
      stripping. A putative signalling network associating these transcripts and six
      microRNAs (hsa-miR, -31, -132, -155, 548c, 548n and 574) was identified using a
      meta-regulation network model. microRNAs not previously associated with IFN
      signalling have been identified. In contrast, only 223 known transcripts were
      significantly changed after imiquimod treatment, including CXCL10, and OAS1.
      CONCLUSION: Results suggest that IFN signalling is important in these
      translational models and novel miRNA may be new targets in the treatment of IFN
      associated skin disease.

PMID- 25596951
TI  - Langerhans Cell Histiocytosis: Diagnosis on Thyroid Aspirate and Review of the
      Literature.
AB  - Thyroid gland involvement by Langerhans cell histiocytosis is extremely rare. A
      35-year-old woman with a history of a suprasellar mass previously diagnosed as a
      ganglioglioma and complicated by diabetes insipidus, hypogonadotropic
      hypogonadism, and central hypothyroidism presented with acute onset of neck
      enlargement. On ultrasound examination, almost the entire thyroid appeared
      replaced by abnormal lobulated hypoechoic tissue with increased vascularity. Fine
      needle aspiration (FNA) of the thyroid was performed and revealed singly
      scattered and loosely cohesive large cells with abundant cytoplasm, including
      some with irregular nuclear contours and nuclear grooves. No thyroid follicular
      cells were noted. Based on the cytomorphologic findings and ancillary studies
      (immunohistochemistry and flow cytometry analysis) a cytological diagnosis of
      "positive for neoplastic cells" with features suggestive of monocytic/histiocytic
      origin, possibly Langerhans cell histiocytosis (LCH) was rendered. Following FNA,
      the patient underwent an incisional thyroid biopsy that confirmed the cytological
      impression of LCH. In light of the new diagnosis of LCH, the prior suprasellar
      mass biopsy slides were re-reviewed and rare cells suspicious for LCH were
      observed. Appropriate treatment for systemic LCH was initiated successfully. This
      case demonstrates that the presence of enlarged and loosely cohesive cells,
      especially those with irregular nuclear contours, in thyroid FNA specimens should
      raise suspicion for LCH. The diagnosis of LCH in FNA specimens is challenging.
      Additional material should be allocated for ancillary studies to confirm the
      morphological impression. In our case, not only was the thyroid FNA crucial in
      diagnosing LCH, but instrumental in initiating a thorough diagnostic work-up for
      multisystem involvement and thus unmasking the true etiology of the patient's
      suprasellar mass and associated endocrinopathies. 

PMID- 25596952
TI  - Effect of gender and race on operative mortality after isolated coronary artery
      bypass grafting.
AB  - Studies examining outcomes after coronary artery bypass grafting (CABG) by gender
      and/or race have shown conflicting results. It remains to be determined if, or
      how, gender and race are independent risk factors for CABG operative mortality.
      Using all consecutive patients who underwent isolated CABG at Baylor University
      Medical Center in Dallas, Texas, from January 2004 to October 2011, the risk
      adjusted associations between gender and race, respectively, and operative
      mortality were estimated using a generalized propensity approach, accounting for
      recognized Society of Thoracic Surgeons risk factors for mortality. Women were
      nearly 2 times more likely to die during or within 30 days of the operation than
      men (odds ratio 1.96, 95% confidence interval 1.44 to 2.66, p <0.0001), while no
      significant mortality differences were observed among races. In conclusion, these
      findings suggest that women face a significantly greater risk for operative death
      that should be taken into account during the treatment decision-making process
      but that race is not associated with CABG mortality and so should not be among
      the factors considered.

PMID- 25596953
TI  - Patients with ischemic mitral regurgitation treated with percutaneous coronary
      intervention.

PMID- 25596955
TI  - Light acclimation optimizes leaf functional traits despite height-related
      constraints in a canopy shading experiment.
AB  - Within-canopy gradients of leaf functional traits have been linked to both light
      availability and vertical gradients in leaf water potential. While observational
      studies can reveal patterns in leaf traits, within-canopy experimental
      manipulations can provide mechanistic insight to tease apart multiple interacting
      drivers. Our objectives were to disentangle effects of height and light
      environment on leaf functional traits by experimentally shading branches along
      vertical gradients within a sugar maple (Acer saccharum) forest. Shading reduced
      leaf mass per area (LMA), leaf density, area-based leaf nitrogen (N(area)), and
      carbon:nitrogen (C:N) ratio, and increased mass-based leaf nitrogen (N(mass)),
      highlighting the importance of light availability on leaf morphology and
      chemistry. Early in the growing season, midday leaf water potential (Psi(mid)),
      LMA, and N(area) were driven primarily by height; later in the growing season,
      light became the most important driver for LMA and Narea. Carbon isotope
      composition (delta(13)C) displayed strong, linear correlations with height
      throughout the growing season, but did not change with shading, implying that
      height is more influential than light on water use efficiency and stomatal
      behavior. LMA, leaf density, N(mass), C:N ratio, and delta(13)C all changed
      seasonally, suggesting that leaf ageing effects on leaf functional traits are
      equally as important as microclimatic conditions. Overall, our results indicate
      that: (1) stomatal sensitivity to vapor pressure deficit or Psi(mid) constrains
      the supply of CO2 to leaves at higher heights, independent of light environment,
      and (2) LMA and N(area) distributions become functionally optimized through
      morphological acclimation to light with increasing leaf age despite height
      related constraints.

PMID- 25596958
TI  - Governance within the World Health Assembly: a 13-year analysis of WHO Member
      States' contribution to global health governance.
AB  - There is a widespread perception that developed countries in the Western world
      dictate the shaping and governance of global health. While there are many bodies
      that engage in global health governance, the World Health Organisation (WHO) is
      the only entity whereby 194 countries are invited to congregate together and
      engage in global health governance on an equal playing field. This paper examines
      the diversity of governance within the World Health Assembly (WHA), the supreme
      decision-making body of the WHO. It explores the degree and balance of policy
      influence between high, middle and low-income countries and the relevance of the
      WHO as a platform to exercise global governance. It finds that governance within
      the WHA is indeed diverse: relative to the number of Member States within the
      regions, all regions are well represented. While developed countries still
      dominate WHA governance, Western world countries do not overshadow decision
      making, but rather there is evidence of strong engagement from the emerging
      economies. It is apparent that the WHO is still a relevant platform whereby all
      Member States can and do participate in the shaping of global health governance. 

PMID- 25596956
TI  - Risk of suicide for individuals reporting asthma and atopy in young adulthood:
      findings from the Glasgow Alumni study.
AB  - There is emerging evidence that asthma and atopy may be associated with a higher
      risk of suicide. We investigated the association of asthma and atopy with
      mortality from suicide (n=32) in the Glasgow Alumni cohort, adjusting for the key
      confounders of socioeconomic position and smoking. We found no evidence of an
      association in our a priori atopy phenotypes with suicide, and there were
      insufficient suicides in the asthma phenotypes to draw any conclusions. In
      additional analyses, individuals reporting both eczema-urticaria and hay fever
      and those with family history of atopy were at higher risk of suicide. As these
      were secondary analyses and based on small numbers of events we cannot rule out
      chance findings. The lack of evidence in our main hypothesis may be due to the
      small number of suicides or reported associations between asthma and atopy may be
      confounded. 

PMID- 25596957
TI  - Video teleconference-based neurocognitive screening in geropsychiatry.
AB  - Validation of remote video teleconference (VTC)-based procedures for
      geropsychiatry applications is essential to ensure validity and reliability of
      diagnostic procedures. The current study demonstrates the similarity of scores
      obtained from several brief neurocognitive screening measures in an outpatient VA
      geropsychiatry clinic population when participants were tested in-person and via
      VTC. Results revealed similar mean scores and moderate to good consistency among
      our mixed geropsychiatric sample on brief measures of global cognition,
      attention, and visuospatial function. 

PMID- 25596959
TI  - Histology and ultrastructure of the coenenchyme of the octocoral Swiftia exserta,
      a model organism for innate immunity/graft rejection.
AB  - The octocoral Swiftia exserta has been utilized extensively in our laboratory to
      study innate immune reactions in Cnidaria such as wound healing, auto- and allo
      graft reactions, and for some classical "foreign body" phagocytosis experiments.
      All of these reactions occur in the coenenchyme of the animal, the colonial
      tissue surrounding the axial skeleton in which the polyps are embedded, and do
      not rely on nematocysts or directly involve the polyps. In order to better
      understand some of the cellular reactions occurring in the coenenchyme, the
      present study employed several cytochemical methods (periodic acid-Schiff
      reaction, Mallory's aniline blue collagen stain, and Gomori's trichrome stain)
      and correlated the observed structures with electron microscopy (both scanning
      and transmission). Eight types of cells were apparent in the coenenchyme of S.
      exserta, exclusive of gastrodermal tissue: (i) epithelial ectoderm cells, (ii)
      oblong granular cells, (iii) granular amoebocytes, (iv) morula-like cells, (v)
      mesogleal cells, (vi) sclerocytes, (vii) axial epithelial cells, and (viii)
      cnidocytes with mostly atrichous isorhiza nematocysts. Several novel
      organizational features are now apparent from transmission electron micrographs:
      the ectoderm consists of a single layer of flat epithelial cells, the cell types
      of the mesoglea extend from beneath the thin ectoderm throughout the mesogleal
      cell cords, the organization of the solenia gastroderm consists of a single layer
      of cells, and two nematocyst types have been found. A new interpretation of the
      cellular architecture of S. exserta, and more broadly, octocoral biology is now
      possible. 

PMID- 25596961
TI  - Combined heart-kidney transplantation after total artificial heart insertion.
AB  - We present the first single-center report of 2 consecutive cases of combined
      heart and kidney transplantation after insertion of a total artificial heart
      (TAH). Both patients had advanced heart failure and developed dialysis-dependent
      renal failure after implantation of the TAH. The 2 patients underwent successful
      heart and kidney transplantation, with restoration of normal heart and kidney
      function. On the basis of this limited experience, we consider TAH a safe and
      feasible option for bridging carefully selected patients with heart and kidney
      failure to combined heart and kidney transplantation. Recent FDA approval of the
      Freedom driver may allow outpatient management at substantial cost savings. The
      TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min,
      may be the mechanical circulatory support device most likely to recover patients
      with marginal renal function and advanced heart failure. 

PMID- 25596962
TI  - Intractable and dramatic diarrhea in liver transplantation recipient with
      vasoactive intestinal peptide-producing tumor after split liver transplantation:
      a case report.
AB  - Diarrhea after liver transplantation is a common complication. Vasoactive
      intestinal peptide-producing tumor (VIPoma) is a rare cause of watery diarrhea;
      80% of such tumors occur in the pancreas, but it is rare in liver. Hypersecretion
      of vasoactive intestinal polypeptide can stimulate intestinal water and
      electrolyte secretion, and patients with VIPoma present with watery diarrhea,
      hypokalemia, and dehydration. Here we report on a 50-year-old man who presented
      with a 7-month history of watery diarrhea. He had undergone an orthotopic split
      liver transplantation for hepatocellular carcinoma in November 2011. Two months
      after the liver transplantation, he presented with watery diarrhea, dehydration,
      and hypokalemia. Antibiotics, immunosuppressive drugs modification, antidiarrheal
      agents, antispasmodics, adsorbents, and fasting were alternately used to control
      the diarrhea, but his symptoms remained unchanged. A chromogranin examination, a
      marker of pancreatic neuroendocrine neoplasm, was positive in the third month of
      the diarrhea history and VIPoma was considered. Treatment with somatostatin
      immediately controlled the diarrhea, but the primary lesion could not be
      identified even after corresponding examinations were completed. In the ninth
      month of diarrhea, a 1 * 1-cm lesion was detected in the right liver by
      ultrasonography. Radiofrequency ablation was performed, and the diarrhea stopped.
      Seventeen months later, the chromogranin level decreased to normal and the
      patient was asymptomatic. Neither the recipient sharing the other liver portion
      nor the donor presented with any symptoms, so we wondered how the tumor occurred.
      It is possible that a small VIPoma lesion existed in the liver donor before the
      transplantation, and that the immunosuppressive drugs induced tumor development.

PMID- 25596963
TI  - Acquired factor XI deficiency: a rare complication after liver transplantation.
AB  - BACKGROUND: A majority of coagulation factors are synthesized in the liver.
      Factor XI (FXI) deficiency (Rosenthal syndrome) is one of the rare inherited
      coagulation disorders with an extremely low risk of transmission by liver
      transplantation (LT). CASE REPORT: We report here the case of a 50-year-old man
      who unknowingly acquired FXI deficiency by LT. During 1 year of post-transplant
      follow-up, his activated partial thromboplastin time (aPTT) remained prolonged,
      but he did not develop bleeding complications. The patient required
      retransplantation due to chronic rejection and is currently doing well 4 years
      after his first liver transplantation. CONCLUSIONS: The presence of a prolonged
      aPTT in a deceased donor should raise suspicion for the presence of rare
      coagulation factor deficiencies. During urgent, lifesaving procedures such as LT,
      it may be impossible to avoid transmission. Awareness of this possibility will
      allow early detection and management.

PMID- 25596960
TI  - Revisiting the "Golden Hour": An Evaluation of Out-of-Hospital Time in Shock and
      Traumatic Brain Injury.
AB  - STUDY OBJECTIVE: We evaluate patients with shock and traumatic brain injury who
      were previously enrolled in an out-of-hospital clinical trial to test the
      association between out-of-hospital time and outcome. METHODS: This was a
      secondary analysis of patients with shock and traumatic brain injury who were
      aged 15 years or older and enrolled in a Resuscitation Outcomes Consortium out-of
      hospital clinical trial by 81 emergency medical services agencies transporting to
      46 Level I and II trauma centers in 11 sites (May 2006 through May 2009).
      Inclusion criteria were systolic blood pressure less than or equal to 70 mm Hg or
      systolic blood pressure 71 to 90 mm Hg with pulse rate greater than or equal to
      108 beats/min (shock cohort) and Glasgow Coma Scale score less than or equal to 8
      (traumatic brain injury cohort); patients meeting both criteria were placed in
      the shock cohort. Primary outcomes were 28-day mortality (shock cohort) and 6
      month Glasgow Outcome Scale-Extended score less than or equal to 4 (traumatic
      brain injury cohort). RESULTS: There were 778 patients in the shock cohort (26%
      28-day mortality) and 1,239 patients in the traumatic brain injury cohort (53% 6
      month Glasgow Outcome Scale-Extended score <=4). Out-of-hospital time greater
      than 60 minutes was not associated with worse outcomes after accounting for
      important confounders in the shock cohort (adjusted odds ratio [aOR] 1.42; 95%
      confidence interval [CI] 0.77 to 2.62) or traumatic brain injury cohort (aOR
      0.77; 95% CI 0.51 to 1.15). However, shock patients requiring early critical
      hospital resources and arriving after 60 minutes had higher 28-day mortality (aOR
      2.37; 95% CI 1.05 to 5.37); this finding was not observed among a similar
      traumatic brain injury subgroup. CONCLUSION: Among out-of-hospital trauma
      patients meeting physiologic criteria for shock and traumatic brain injury, there
      was no association between time and outcome. However, the subgroup of shock
      patients requiring early critical resources and arriving after 60 minutes had
      higher mortality.

PMID- 25596964
TI  - The effects of physical activity on sleep: a meta-analytic review.
AB  - A significant body of research has investigated the effects of physical activity
      on sleep, yet this research has not been systematically aggregated in over a
      decade. As a result, the magnitude and moderators of these effects are unclear.
      This meta-analytical review examines the effects of acute and regular exercise on
      sleep, incorporating a range of outcome and moderator variables. PubMed and
      PsycINFO were used to identify 66 studies for inclusion in the analysis that were
      published through May 2013. Analyses reveal that acute exercise has small
      beneficial effects on total sleep time, sleep onset latency, sleep efficiency,
      stage 1 sleep, and slow wave sleep, a moderate beneficial effect on wake time
      after sleep onset, and a small effect on rapid eye movement sleep. Regular
      exercise has small beneficial effects on total sleep time and sleep efficiency,
      small-to-medium beneficial effects on sleep onset latency, and moderate
      beneficial effects on sleep quality. Effects were moderated by sex, age, baseline
      physical activity level of participants, as well as exercise type, time of day,
      duration, and adherence. Significant moderation was not found for exercise
      intensity, aerobic/anaerobic classification, or publication date. Results were
      discussed with regards to future avenues of research and clinical application to
      the treatment of insomnia.

PMID- 25596966
TI  - Mechanical and photoelastic analysis of four different fixation methods for
      mandibular body fractures.
AB  - OBJECTIVE: The aim of the present study was to compare four methods of fixation
      in mandibular body fractures. STUDY DESIGN: Mechanical and photoelastic tests
      were performed using polyurethane and photoelastic resin mandibles, respectively.
      The study groups contained the following: (I), two miniplates of 2.0 mm; (II) one
      2.0 mm plate and an Erich arch bar; (III) one 2.4 mm plate and an Erich arch bar,
      and (IV) one 2.0 mm plate and one 2.4 mm plate. The differences between the mean
      values were analyzed using Tukey's test, the Mann-Whitney test and the Bonferroni
      correction. RESULTS: Group II recorded the lowest resistance, followed by groups
      I, IV and III. The photoelastic test confirmed the increase of tension in group
      II. CONCLUSION: The 2.4 mm system board in linear mandibular body fractures
      provided more resistance and the use of only one 2.0 mm plate in the central area
      of the mandible created higher tension.

PMID- 25596965
TI  - Unbound unconjugated hyperbilirubinemia is associated with central apnea in
      premature infants.
AB  - OBJECTIVE: To evaluate whether jaundice, indexed by unbound bilirubin (UB), is
      associated with central apnea in premature infants. STUDY DESIGN: A prospective
      observational study was performed with 27-33 weeks' gestational age infants who
      were not requiring either mechanical ventilation or noninvasive ventilation with
      continuous positive airway pressure beyond 24 hours after birth. Infants with
      congenital infections, chromosomal disorders, craniofacial anomalies, and/or
      family history of hearing loss were excluded. Total serum bilirubin and UB were
      measured twice daily during the first postnatal week and then when clinically
      indicated. Central apnea was evaluated by visual inspection of continuous,
      electronic cardiorespiratory recordings until 2 weeks of age. RESULTS: One
      hundred infants were subdivided into 2 groups via median peak UB level: the high
      UB group (greater than median) and low UB group (less than median). The high UB
      group had an increased frequency of apnea events during the first 2 weeks
      compared with infants in the low UB group. After we controlled for confounders,
      the high UB group had more events of apnea during the first 2 postnatal weeks
      compared with the low UB group (incidence rate ratio: 1.9, 95% CI 1.2-3.2).
      CONCLUSIONS: Our findings suggest that jaundice, as indexed by UB, is associated
      with central apnea in premature infants.

PMID- 25596967
TI  - Biological monitoring of IFN-beta therapy in Multiple Sclerosis.
AB  - Multiple Sclerosis (MS) is a heterogeneous disease and a variable percentage of
      patients are non-responders to common treatment. Early diagnosis of non
      responders allows change to a more useful therapy for the patient and better
      allocates a large amount of financial resources. Quantification of Neutralizing
      antibodies (Nabs) and of biological activity of IFN-beta are recognized
      approaches to identify immuno-pharmacological non-responders. A consistent number
      of studies have demonstrated that quantification of Myxovirus-induced protein A
      (MxA) is a valid biomarker to detect immune-pharmacological non responders after
      one year of treatment. Persistent high titre of Nabs and absence of biological
      activity predict abolition of IFN-beta effects in disease activity measured
      through MRI, number of relapses and disability. Guidelines and flow-charts
      including both Nabs and MxA quantification are presented. 

PMID- 25596968
TI  - Combination siRNA therapy against feline coronavirus can delay the emergence of
      antiviral resistance in vitro.
AB  - Virulent biotypes of feline coronavirus (FCoV), commonly referred to as feline
      infectious peritonitis virus (FIPV), can result in the development of feline
      infectious peritonitis (FIP), a typically fatal immune mediated disease for which
      there is currently no effective antiviral treatment. We previously reported the
      successful in vitro inhibition of FIPV replication by synthetic siRNA mediated
      RNA interference (RNAi) in an immortalised cell line (McDonagh et al., 2011). A
      major challenge facing the development of any antiviral strategy is that of
      resistance, a problem which is particularly acute for RNAi based therapeutics due
      to the exquisite sequence specificity of the targeting mechanism. The development
      of resistance during treatment can be minimised using combination therapy to
      raise the genetic barrier or using highly potent compounds which result in a more
      rapid and pronounced reduction in the viral replication rate, thereby reducing
      the formation of mutant, and potentially resistant viruses. This study
      investigated the efficacy of combination siRNA therapy and its ability to delay
      or prevent viral escape. Virus serially passaged through cells treated with a
      single or dual siRNAs rapidly acquired resistance, with mutations identified in
      the siRNA target sites. Combination therapy with three siRNA prevented viral
      escape over the course of five passages. To identify more potent silencing
      molecules we also compared the efficacy, in terms of potency and duration of
      action, of canonical versus Dicer-substrate siRNAs for two previously identified
      effective viral motifs. Dicer-substrate siRNAs showed equivalent or better
      potency than canonical siRNAs for the target sites investigated, and may be a
      more appropriate molecule for in vivo use. Combined, these data inform the
      potential therapeutic application of antiviral RNAi against FIPV. 

PMID- 25596969
TI  - Differential effects of alloherpesvirus CyHV-3 and rhabdovirus SVCV on apoptosis
      in fish cells.
AB  - Whilst Herpesviridae, which infect higher vertebrates, actively influence host
      immune responses to ensure viral replication, it is mostly unknown if
      Alloherpesviridae, which infect lower vertebrates, possess similar abilities. An
      important antiviral response is clearance of infected cells via apoptosis, which
      in mammals influences the outcome of infection. Here, we utilise common carp
      infected with CyHV-3 to determine the effect on the expression of genes encoding
      apoptosis-related proteins (p53, Caspase 9, Apaf-1, IAP, iNOS) in the pronephros,
      spleen and gills. The influence of CyHV-3 on CCB cells was also studied and
      compared to SVCV (a rhabdovirus) which induces apoptosis in carp cell lines.
      Although CyHV-3 induced iNOS expression in vivo, significant induction of the
      genetic apoptosis pathway was only seen in the pronephros. In vitro CyHV-3 did
      not induce apoptosis or apoptosis-related expression whilst SVCV did stimulate
      apoptosis. This suggests that CyHV-3 possesses mechanisms similar to
      herpesviruses of higher vertebrates to inhibit the antiviral apoptotic process. 

PMID- 25596970
TI  - Association of DNMT1 Gene Polymorphisms with Congenital Heart Disease in Child
      Patients.
AB  - To reveal the association between DNMT1 polymorphisms and congenital heart
      disease (CHD) in child patients, a total of 224 CHD child patients as well as 199
      healthy individuals were enrolled in the present study. The DNA was extracted
      from whole blood, and four SNPs including rs16999593, rs2228612, rs2288349 and
      rs10420321 were selected for the gene polymorphism investigation via ligase
      detection reaction (LDR) assay. Odds ratios (ORs) and 95 % confidence intervals
      (95 % CIs) were used to assess the strength of the association. rs16999593 was
      associated with the CHD under the heterozygous (CT vs TT: OR 0.62; 95 % CI 0.41
      0.95; p = 0.03), dominant (CT + CC vs TT: OR 0.63; 95 % CI 0.42-0.95; p = 0.03),
      and allele models (C vs T: OR 0.07; 95 % CI 0.50-1.00; p = 0.05). rs2228612 was
      related with the CHD under the heterozygous (AG vs AA: OR 0.42; 95 % CI 0.27
      0.65; p = 0.0001), homozygous (GG vs AA: OR 0.43; 95 % CI 0.240-0.77; p = 0.004),
      dominant (AG + GG vs AA: OR 0.42; 95 % CI 0.28-0.64; p < 0.0001), and allele
      models (G vs A: OR 0.62; 95 % CI 0.47-0.82; p = 0.0007). rs10420321 correlated
      with the CHD only under the recessive model (GG vs AG + AA: OR 0.61; 95 % CI 0.37
      1.01, p = 0.05). However, no significant association between the rs2288349
      polymorphisms and the risk of CHD was observed (p > 0.05). DNMT1 polymorphisms
      might contribute to the risk of CHD, especially rs16999593 and rs2228612.

PMID- 25596971
TI  - Second opinion.

PMID- 25596972
TI  - Vertebral artery (V2) pseudo-aneurysm after surgery for cervical schwannoma. How
      to prevent it and a review of the literature.
AB  - STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To prevent and
      manage a suspected iatrogenic vertebral artery injury during a cervical spine
      anterior approach. SUMMARY OF BACKGROUND DATA: The anterior spine approach is a
      common surgery with few complications. One of the rare but significant risks is
      vertebral artery injury. Consequences of vertebral artery injuries are often
      delayed. Therefore, it is essential to prevent this complication and to know how
      when exploring after a suspected vertebral artery injury. METHODS: Report of a
      case and review of the literature. A 61-year-old woman presented with a cervical
      schwannoma involving the C5-C6 foramen. She had undergone surgery 22 years before
      by the posterior approach. We performed an anterior cervical approach. After 12
      days, a vertebral artery pseudo-aneurysm occurred. Our review of the literature
      is focalized on vertebral artery injuries during cervical surgery by the anterior
      approach. RESULTS: The patient was treated by coil embolization with a good
      outcome. To our knowledge, only 6 cases of vertebral artery pseudo-aneurysm after
      surgery have been reported in the literature. CONCLUSION: According to the
      literature, vertebral artery pseudo-aneurysms resulting in anterior cervical
      approach are rare but their consequences could be severe. Prevention begins by
      detailed surgical planning. Peroperative imaging is helpful. Any suspected
      vertebral artery injury should postpone a contralateral approach before
      angiographic imaging.

PMID- 25596973
TI  - From "mechanical" to "neuropathic" back pain concept in FBSS patients. A
      systematic review based on factors leading to the chronification of pain (part
      C).
AB  - INTRODUCTION: Beyond initial lesions, any form of spinal (re)operation can cause
      direct potential aggression to the nervous system by contact with neural tissue
      or by imprinting a morphological change on the neural tissue. The potential
      consequences of nerve root injury affect both peripheral and axial dermatomal
      distribution. The hypothesis of a possible neuropathic aspect associated with the
      back pain component of failed back surgery syndrome (FBSS) therefore appears to
      be reasonable. Its pathophysiology remains unclear due to the permanent interplay
      between nociceptive and neuropathic pain components, resulting in the coexistence
      of physiological and pathological pain at the same anatomical site. This paper is
      designed to extensively review the fundamental mechanisms leading to
      chronification of pain and to suggest considering the emerging concept of
      "neuropathic back pain". METHODS: Literature searches included an exhaustive
      review of 643 references and 74 book chapters updated by searching the major
      electronic databases from 1930 to August 2013. RESULTS: Inflammatory and
      neuropathic back pain could be distinguished from pure nociceptive pain as a
      result of an increased activity and responsiveness of sensitized receptors at the
      peripheral nervous system and also as a consequence of increased afferent inflow
      to the central nervous system, moving to a new, more excitable "wind-up" state.
      This can be clinically translated to an amplified response to a moderate/intense
      stimulus (primary hyperalgesia) or an aversive sensation provoked by the
      activation of low-threshold mechanoreceptors through non-noxious stimuli, which
      defines allodynia. Activated non-neuronal cells including microglia have been
      found to be cellular intermediaries in mechanical allodynia. Major changes in the
      spinal cord are the loss of inhibitory mechanisms, resulting in an increased
      activity of interneurons or projection neurons and a structural reorganization of
      the central projection pattern. This abnormal excitability of sensory neurons is
      coupled to changes in the neurotransmitter phenotype, which could induce a
      resistance to conventional analgesic treatments. CONCLUSION: A clear
      understanding of the factors leading to the chronification of back pain should
      help us to move to the choice of mechanism related pain treatments to improve
      outcomes in FBSS chronic condition.

PMID- 25596974
TI  - Hepatitis research in Arab countries: questions needing answers.

PMID- 25596975
TI  - Predictive factors of morbidity after surgical treatment of hydatid cyst of the
      liver.
AB  - BACKGROUND AND STUDY AIMS: Hepatic hydatid cyst is a major health problem in
      endemic areas. Surgery is still the best choice for treatment of the hydatid cyst
      of the liver. However, it is still associated with high mortality and morbidity.
      The aim of the study was to evaluate the predictive factors for specific
      morbidity after conservative surgical treatment of the hydatid cyst of the liver.
      PATIENTS AND METHODS: A total of 120 patients who underwent conservative surgical
      treatment between 2001 and 2011 were evaluated retrospectively. RESULTS: Of the
      120 patients, 64 were female subjects and 56 male subjects; the median age was 33
      years (14-83 years). The mortality rate was 0%. The overall morbidity rate was
      26.6%. The specific morbidity rate was 16.6%. The major specific complications
      were infection of the residual cavity in 10 cases and an external biliary fistula
      in eight cases. The predictive factors of morbidity in univariate analysis were
      bilious cyst content, location of the cyst in the hepatic dome, and size >10 cm.
      After multivariate analysis, only the size of the cyst was an independent
      predictive factor of morbidity. CONCLUSION: The size of the cyst was the
      significant predictor of morbidity of conservative surgery for liver hydatid
      cyst.

PMID- 25596976
TI  - Refractory ascites as the first presentation of systemic lupus erythematosus.
AB  - Serositis (peritonitis, pleuritis, and pericarditis) can be observed in
      approximately 13% of patients with systemic lupus erythematosus (SLE). However,
      peritoneal serositis presenting as painless massive ascites is extremely rare
      with only few cases been reported. Indeed, ascites in SLE has been reported to
      occur only when complicated by nephrotic syndrome, congestive cardiac failure, or
      portal hypertension. We describe herein a very unique case of SLE related
      serositis presenting with a massive refractory ascites, normal albumin, and
      absence of a clear autoimmune disorder or protein-losing enteropathy (PLE) at the
      time of her presentation, which only responded to a pulse course of
      corticosteroid. SLE was confirmed 2 years later.

PMID- 25596977
TI  - Nationwide survey of the development of drug resistance in the pediatric field in
      2000-2001, 2004, 2007, 2010, and 2012: evaluation of the changes in drug
      sensitivity of Haemophilus influenzae and patients' background factors.
AB  - The Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease
      has conducted surveillance of pediatric patients with respiratory tract
      infections, meningitis, and sepsis five times (in 2000-2001 [period 1], 2004
      [period 2], 2007 [period 3], 2010 [period 4], and 2012 [period 5]). With respect
      to the clinically isolated Haemophilus influenzae, the drug susceptibility, the
      frequency of drug-resistant strains, and patients' background factors in each
      period have already been reported. Here we evaluate trends in the development of
      drug resistance in H. influenzae, and the relationship between the development of
      drug resistance and patients' background factors in the aforementioned five
      periods. H. influenzae derived from pediatric patients with respiratory tract
      infections that had been previously collected (period 1, 448 isolates; period 2,
      376 isolates; period 3, 386 isolates; period 4, 484 isolates; and period 5, 411
      isolates) were analyzed. The proportions of beta-lactamase-nonproducing
      ampicillin (ABPC)-intermediate resistant (BLNAI) strains + beta-lactamase
      nonproducing ABPC-resistant (BLNAR) strains were 28.8% in period 1, 59.3% in
      period 2, 61.1% in period 3, 58.1% in period 4, and 63.5% in period 5, showing a
      rapid increase from period 1 to period 2 followed by an almost constant rate of
      approximately 60%. The proportion of beta-lactamase-producing ABPC-resistant
      (BLPAR) strains + beta-lactamase-producing clavulanic acid/amoxicillin-resistant
      (BLPACR) strains was 4.4% in period 3, which was somewhat low; however, there
      were no significant changes in the proportions of these strains, which ranged
      between 6.4% and 8.7% throughout the surveillance period except for period 3. The
      drugs whose MIC90 values against BLNAR strains were low throughout the
      surveillance included piperacillin (0.25 MUg/mL) and tazobactam/piperacillin
      (0.125-0.25 MUg/mL) in the penicillins; cefditoren and ceftriaxone (0.25-0.5
      MUg/mL for both) in the cephems; meropenem (0.5-1 MUg/mL) and tebipenem (1
      MUg/mL) in the carbapenems; and levofloxacin, tosufloxacin, and garenoxacin (<=
      0.06 MUg/mL for all) and norfloxacin (0.06-0.125 MUg/mL) in the quinolones. We
      investigated the relationship between the frequency of BLNAS strains/BLNAI +
      BLNAR strains and patients' background factors in each surveillance period.
      Significant differences were shown on age category (< 3 years or >= 3 years) in
      all periods except period 4, and the presence/absence of prior administration of
      antimicrobial agents within one month in period 2 and period 3. In all periods,
      the frequency of BLNAI + BLNAR strains were higher in patients aged < 3 years
      than in patients aged >= 3 years, and were also higher in patients with presence
      of prior treatment than in patients without prior treatment. We consider that it
      is important to promote the proper use of antimicrobial agents by conducting
      surveillance continuously in the future to clarify the relationship between the
      development of drug resistance in H. influenzae and patients' background factors
      and provide those information to clinical setting.

PMID- 25596978
TI  - The association of perioperative transfusion with 30-day morbidity and mortality
      in patients undergoing major vascular surgery.
AB  - OBJECTIVE: Blood transfusions are common among patients undergoing major vascular
      surgery. Prior studies suggest an association between blood transfusion and
      increased morbidity and mortality among patients undergoing cardiac surgery. The
      predictors of perioperative transfusion and its impact on patients undergoing
      vascular surgery have been poorly defined. METHODS: We examined data from a large
      multicenter quality improvement vascular surgical registry of all patients
      undergoing elective or urgent open peripheral arterial disease procedures,
      endovascular aneurysm repair, or open abdominal aortic aneurysm (AAA) repair
      between January 2012 and December 2013. Emergency cases, carotid endarterectomy,
      and carotid artery stenting were excluded. Univariate and multivariate logistic
      regression modeling was used to identify predictors of transfusion and
      association of transfusion with outcomes. All regression models had Hosmer
      Lemeshow P > .05 and area under the receiver operating characteristic curve of
      >0.8, confirming excellent goodness of fit and discrimination. RESULTS: Our study
      population comprised 2946 patients who underwent open peripheral arterial disease
      procedures (n = 1744), open AAA repair (n = 175), or endovascular aneurysm repair
      (n = 1027) at 22 hospitals. The overall transfusion rate was 25%, at a median
      nadir hemoglobin level of 7.7 g/dL. Independent factors predicting transfusion
      included female gender (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.1
      3.2), nonwhite race (OR, 2.7; 95% CI, 1.4-5.2), preoperative admission status
      (ie, acute care hospital) (OR, 2.6; 95% CI, 1.3-5.3), preoperative anemia (OR,
      4.2; 95% CI, 3.3-5.1), congestive heart failure (OR, 1.4; 95% CI, 1.1-1.9), prior
      myocardial infarction (OR, 1.3; 95% CI, 1.01-1.6), clopidogrel (OR, 1.4; 95% CI,
      1.2-1.8), open AAA repair (OR, 25; 95% CI, 17-39), open bypass (OR, 3.5; 95% CI,
      2.7-4.6), and urgent procedures (OR, 1.4; 95% CI, 1.1-1.8). With adjustment for
      major covariates, perioperative transfusion was independently associated with
      death (OR, 6.9; 95% CI, 3.2-15), myocardial infarction (OR, 8; 95% CI, 3.7-17),
      and pneumonia (OR, 7.4; 95% CI, 3.3-17). CONCLUSIONS: Perioperative transfusion
      in vascular surgical patients is independently associated with increased 30-day
      morbidity and mortality. Given indeterminate causation, these data suggest the
      need for a prospective transfusion threshold study in vascular surgical patients.

PMID- 25596980
TI  - Mike Stroud: exploring nutrition at the limits of endurance.

PMID- 25596981
TI  - Posterolateral knee reconstruction.
AB  - Injury to the cruciate ligaments of the knee commonly occurs in association with
      posterolateral instability, which can cause severe functional disability
      including varus, posterior translation, and external rotational instability.
      Failure to diagnose and treat an injury of the posterolateral corner in a patient
      who has a tear of the cruciate ligament can also result in the failure of the
      reconstructed cruciate ligament. There seems to be a consensus of opinion that
      injury to the posterolateral corner, whether isolated or combined, is best
      treated by reconstructing the posterolateral corner along with the coexisting
      cruciate ligament injury, if combined. Commonly proposed methods of
      reconstructing the posterolateral corner have focused on the reconstruction of
      the popliteus, the popliteofibular ligament, and the lateral collateral ligament.
      The aim of this conference is to describe the posterolateral corner
      reconstruction technique and to provide an algorithm of treatment. 

PMID- 25596982
TI  - Management of recent first-time anterior shoulder dislocations.
AB  - The management of a first episode of anterior shoulder dislocation starts with an
      analysis of the causative mechanism and a physical examination to establish the
      diagnosis. Based on the findings, the case can be classified as simple or
      accompanied with complications, most notably vascular or nerve injuries. Two
      radiographs perpendicular to each other should be obtained to confirm the
      diagnosis then repeated after the reduction manoeuvres. Additional imaging
      studies may be needed to assess concomitant bony lesions (impaction lesions or
      fractures). External reduction should always be attempted after premedication
      appropriate for the severity of the pain. General anaesthesia may be necessary.
      There is no consensus regarding the optimal reduction technique, although the
      need for gentle manoeuvres that do not cause pain is universally recognised.
      Immobilisation currently involves keeping the elbow by the side with the arm
      internally rotated for 3-6weeks depending on patient age. Vessel and nerve
      injuries are rare but can cause major functional impairments. Follow-up
      evaluations are in order to check the recovery of normal function, which may be
      more difficult to achieve in patients with concomitant lesions; and to detect
      recurrent shoulder instability and rotator cuff lesions. At the acute phase,
      surgery is indicated only in patients with complications or after failure of the
      reduction manoeuvres. Shoulder immobilisation with the arm externally rotated and
      surgical treatment of the first episode are controversial strategies that are
      discussed herein. 

PMID- 25596983
TI  - Surgery in vertebral fracture: epidemiology and functional and radiological
      results in a prospective series of 518 patients at 1 year's follow-up.
AB  - INTRODUCTION: Recent epidemiological data for spinal trauma in France are sparse.
      However, increased knowledge of sagittal balance and the development of minimally
      invasive techniques have greatly improved surgical management. OBJECTIVES: To
      describe the epidemiology and management of traumatic vertebral fracture, and to
      analyze evolution and risk factors for poor functional outcome at 1 year's follow
      up. MATERIALS AND METHODS: A prospective multicenter French cohort study was
      performed over a 6-month period in 2011, including all cases of vertebral
      fracture surgery. Data were collected by online questionnaire over the Internet.
      Demographic characteristics, lesion type and surgical procedures were collected.
      Clinical, functional and radiological assessment was carried out at 1 year.
      RESULTS: Five hundred and eighteen patients, with a mean age of 47 years, were
      included. Sixty-seven percent of fractures involved the thoracic or lumbar
      segment. Thirty percent of patients had multiple fractures and 28% neurological
      impairment. A minimally invasive technique was performed in 20% of cases and
      neurological decompression in 25%. Dural tear was observed in 42 patients (8%).
      Seventy percent of patients were followed up at 1 year. Functionally, SF-36
      scores decreased on all dimensions, significantly associated with age, persistent
      neurological deficit and previous spine imbalance. Thirty-eight percent of
      working patients had returned to work. Radiologically, sagittal balance was good
      in 74% of cases, with fracture consolidation in 70%. DISCUSSION: Despite progress
      in management, spinal trauma was still a source of significant morbidity in 2011,
      with pronounced decrease in quality of life. Conserved sagittal balance appeared
      to be associated with better functional outcome.

PMID- 25596984
TI  - Femoral head diameter considerations for primary total hip arthroplasty.
AB  - The configuration of total hip arthroplasty (THA) implants has constantly evolved
      since they were first introduced. One of the key components of THA design is the
      diameter of the prosthetic femoral head. It has been well established that the
      risk of dislocation is lower as the head diameter increases. But head diameter
      impacts other variables beyond joint stability: wear, cam-type impingement, range
      of motion, restoration of biomechanics, proprioception and groin pain. The
      introduction of highly cross-linked polyethylene and hard-on-hard bearings has
      allowed surgeons to implant large-diameter heads that almost completely eliminate
      the risk of dislocation. But as a result, cup liners have become thinner. With
      femoral head diameters up to 36 mm, the improvement in joint range of motion,
      delay in cam-type impingement and reduction in dislocation risk have been clearly
      demonstrated. Conversely, large-diameter heads do not provide any additional
      improvements. If an "ecologically sound" approach to hip replacement is embraced
      (e.g. keeping the native femoral head diameter), hip resurfacing with a metal-on
      metal bearing must be carried out. The reliability of large-diameter femoral
      heads in the longer term is questionable. Large-diameter ceramic-on-ceramic
      bearings may be plagued by the same problems as metal-on-metal bearings: groin
      pain, squeaking, increased stiffness, irregular lubrication, acetabular loosening
      and notable friction at the Morse taper. These possibilities require us to be
      extra careful when using femoral heads with a diameter greater than 36 mm.

PMID- 25596985
TI  - Glenoid labrum pathology.
AB  - The glenoid labrum is the fibrocartilage of the shoulder joint, anchoring the
      joint capsule and shoulder ligaments. Morphology varies regionally, especially in
      the superior and anterior region; these variants can sometimes be confused with
      pathological aspects. The labrum is often involved in shoulder pathology, by
      single trauma or, more often, repeated microtrauma. It seems logical to classify
      and to describe tears according to two criteria: the sector involved, and
      associated pain or instability. In the superior labrum, SLAP lesions are the most
      frequent. These combine labral lesion and lesion of the proximal insertion of the
      long head of the biceps brachii tendon. The most frequent form is SLAP II. They
      may be associated with instability or not. In the antero-inferior and postero
      inferior labrum, lesions are mainly due to instability, particularly Bankart
      lesions (capsulolabral avulsion) anteriorly and Kim's lesion posteriorly.
      Circumferential labral lesions may be found in unstable shoulder. Finally,
      postero-superior lesions involve Walch's internal impingement: repeated contact
      between the deep surface of the cuff and the labrum, which takes on a
      degenerative aspect, with a kissing lesion of the cuff. There is no general rule
      for management: some labral lesions are resected and others fixed. The cause
      (which is usually shoulder instability), however, needs to be assessed and
      treated.

PMID- 25596986
TI  - Wrist osteoarthritis.
AB  - Painful wrist osteoarthritis can result in major functional impairment. Most
      cases are related to posttraumatic sequel, metabolic arthropathies, or
      inflammatory joint disease, although wrist osteoarthritis occurs as an idiopathic
      condition in a small minority of cases. Surgery is indicated only when
      conservative treatment fails. The main objective is to ensure pain relief while
      restoring strength. Motion-preserving procedures are usually preferred, although
      residual wrist mobility is not crucial to good function. The vast array of
      available surgical techniques includes excisional arthroplasty, limited and total
      fusion, total wrist denervation, partial and total arthroplasty, and rib
      cartilage graft implantation. Surgical decisions rest on the cause and extent of
      the degenerative wrist lesions, degree of residual mobility, and patient's wishes
      and functional demand. Proximal row carpectomy and four-corner fusion with
      scaphoid bone excision are the most widely used surgical procedures for stage II
      wrist osteoarthritis secondary to scapho-lunate advanced collapse (SLAC) or
      scaphoid non-union advanced collapse (SNAC) wrist. Proximal row carpectomy is not
      indicated in patients with stage III disease. Total wrist denervation is a
      satisfactory treatment option in patients of any age who have good range of
      motion and low functional demands; furthermore, the low morbidity associated with
      this procedure makes it a good option for elderly patients regardless of their
      range of motion. Total wrist fusion can be used not only as a revision procedure,
      but also as the primary surgical treatment in heavy manual labourers with wrist
      stiffness or generalised wrist-joint involvement. The role for pyrocarbon
      implants, rib-cartilage graft implantation, and total wrist arthroplasty remains
      to be determined, given the short follow-ups in available studies. 

PMID- 25596987
TI  - Viscosupplementation: techniques, indications, results.
AB  - Viscosupplementation by hyaluronic acid (HA) injections is frequently used for
      local treatment of osteoarthritis (OA), due to ease of use and good tolerance. A
      profusion of linear or reticulated HA derivates are marketed, with varied
      characters and levels of evidence. Viscosupplementation has demonstrated moderate
      but significant efficacy (20%) versus placebo in terms of pain and function, with
      a high rate of responders (60-70%) in knee osteoarthritis. It allows reduced
      administration of opioid analgesics and NSAIDs, with improved risk/benefit ratio,
      and may delay joint replacement. Cartilage protection remains to be proven.
      Clinical efficacy shows 1-4 weeks' later onset than corticosteroids, but is
      maintained for 6 or even 12 months. Systematic association of corticosteroid and
      HA injection is not justified, and an interval has to be left before undertaking
      arthroplasty. Intra-articular injection of HA requires a skilled specialist, and
      may be difficult in a non-swollen joint; some tips and tricks may be helpful. In
      other joints than the knee, radiologic or ultrasound guidance is recommended. The
      efficacy of viscosupplementation is a matter of ongoing debate, after discordant
      findings in some meta-analyses. Some poor results may be due to inappropriate use
      of HA injections, poorly adapted to the patient's OA phenotype.
      Viscosupplementation is a treatment for chronic moderate symptomatic OA, and not
      for flares with joint swelling. Application in sport-related chondropathy has yet
      to be properly assessed. The optimal response profile remains to be determined.
      The ideal indication in the knee seems to be moderate femorotibial OA without
      swelling. Results have been generally disappointing in hip osteoarthritis but
      promising in OA of the ankle and shoulder (with and without rotator cuff tear).
      Further studies are needed to determine response profile and optimal treatment
      schedule, according to the joint. 

PMID- 25596988
TI  - A grounded exploration of the dimensions of managerial capability: A preliminary
      study of top Australian pharmacist owner-managers.
AB  - BACKGROUND: Australian community pharmacies are experiencing challenges,
      including government prescription pricing reform and a dramatically increasing
      competitive environment. Enacting appropriate responsive actions requires capable
      pharmacy managers. 'Capability' implies managing effectively in the present, but
      with unknown or emerging contexts and with new problems. A conceptual
      understanding of managerial capability as practiced by pharmacist owner-managers
      is unavailable in the literature. OBJECTIVES: This research aimed to address the
      question: How can we understand managerial capability in relation to effective
      community pharmacy management? The study's objective was to develop preliminary
      theoretical departure points for continuing research responding to the research
      question. METHODS: The objective was approached by exploring how 5 top Australian
      pharmacy owner-managers accomplish the management of their businesses in a
      changing business environment. Qualitative research methods were employed to
      develop a social process perspective of how the managers enact their management
      practices. In-depth semi-structured life-world interviews were undertaken as the
      major method of data collection. Interview text thematic analysis was carried out
      identifying rich conceptual properties and dimensions, which 'dimensionalized' 3
      key integrated categories. RESULTS: The findings show how the managers are
      immersed in their business, managerial and personal practices in a holistic and
      relational manner. Managerial processes, reported through three conceptual
      categories, their properties and dimensions, reveal the highly situational nature
      of the reality the managers were experiencing, including their need to express
      their personal/professional identity. The properties and dimensions of the
      category 'learning generatively' in particular, reveal how the pharmacy owner
      managers shape their business activities and their emerging context as time
      passes. CONCLUSIONS: The preliminary interpretive view of managerial capability
      describes the phenomenon as an emergent human accomplishment rather than a
      possessed ability. This social process perspective enables the inclusion of
      context with time. The study acts as a formative departure point for continuing
      research of pharmacist managerial capability which seeks to better understand the
      linkage between 'knowing' and 'doing'.

PMID- 25596989
TI  - Prognostic Factors in Non-Small Cell Lung Cancer Less Than 3 Centimeters:
      Actuarial Analysis, Accumulative Incidence and Risk Groups.
AB  - INTRODUCTION: In TNM classification, factors determining the tumor (T) component
      in non-small cell lung cancer have scarcely changed over time and are still based
      solely on anatomical features. Our objective was to study the influence of these
      and other morphopathological factors on survival. METHODS: A total of 263
      patients undergoing lung resection due to stage I non-small cell lung cancer
      <=3cm in diameter were studied. A survival analysis and competing-risk estimate
      study was made on the basis of clinical, surgical and pathological variables
      using actuarial analysis and accumulative incidence methods, respectively. A risk
      model was then generated from the results. RESULTS: Survival at 5 and 10 years
      was 79.8 and 74.3%, respectively. The best prognostic factors were presence of
      symptoms, smoking habit and FEV1>60%, number of resected nodes>7, squamous
      histology, absence of vascular invasion, absence of visceral pleural invasion and
      presence of invasion more proximal than the lobar bronchus. All these were
      statistically significant according to the actuarial method. The factor "age<50
      years" was close to the margin of statistical significance. Pleural invasion and
      vascular invasion were entered in the multivariate analysis. The competing-risk
      analysis showed a probability of death due to cancer of 14.3 and 35.1% at 5 and
      10 years, respectively. Significant variables in the univariate and multivariate
      analyses were similar, with the exception of FEV1>60%. CONCLUSIONS: Pleural
      invasion and vascular invasion determine survival or risk of death due to non
      small cell lung cancer <=3cm and can be used for generating a predictive risk
      model.

PMID- 25596990
TI  - Dyspnea in a pneumonectomized patient.

PMID- 25596992
TI  - Hematic pleural effusion in a 17-year-old woman.

PMID- 25596993
TI  - Contributions of the high resolution computed tomography in the early detection
      of silicosis.

PMID- 25596991
TI  - ALAT-2014 Chronic Obstructive Pulmonary Disease (COPD) Clinical Practice
      Guidelines: questions and answers.
AB  - ALAT-2014 COPD Clinical Practice Guidelines used clinical questions in PICO
      format to compile evidence related to risk factors, COPD screening, disease
      prognosis, treatment and exacerbations. Evidence reveals the existence of risk
      factors for COPD other than tobacco, as well as gender differences in disease
      presentation. It shows the benefit of screening in an at-risk population, and the
      predictive value use of multidimensional prognostic indexes. In stable COPD,
      similar benefits in dyspnea, pulmonary function and quality of life are achieved
      with LAMA or LABA long-acting bronchodilators, whereas LAMA is more effective in
      preventing exacerbations. Dual bronchodilator therapy has more benefits than
      monotherapy. LAMA and combination LABA/IC are similarly effective, but there is
      an increased risk of pneumonia with LABA/IC. Data on the efficacy and safety of
      triple therapy are scarce. Evidence supports influenza vaccination in all
      patients and anti-pneumococcal vaccination in patients <65years of age and/or
      with severe airflow limitation. Antibiotic prophylaxis may decrease exacerbation
      frequency in patients at risk. The use of systemic corticosteroids and
      antibiotics are justified in exacerbations requiring hospitalization and in some
      patients managed in an outpatient setting. 

PMID- 25596994
TI  - DOG1, cyclin D1, CK7, CD117 and vimentin are useful immunohistochemical markers
      in distinguishing chromophobe renal cell carcinoma from clear cell renal cell
      carcinoma and renal oncocytoma.
AB  - The distinction between chromophobe renal cell carcinoma (ChRCC), clear cell
      renal cell carcinoma (CRCC) and renal oncocytoma may cause a diagnostic dilemma.
      The usefulness of DOG1, cyclin D1, CK7, CD117 and vimentin in the differential
      diagnosis of these renal epithelial tumors was investigated. DOG1 was positive in
      ChRCC (32 of 32, 100%) and in renal oncocytoma (21 of 21, 100%). In contrast,
      DOG1 was absent in all CRCC (0 of 30). Cyclin D1 was positive in renal
      oncocytomas (17 of 21, 81%) but negative in the ChRCC (0/23) and CRCC (0 of 30).
      CK7 was positive in ChRCC (30 of 32, 94%), but was negative in oncocytoma (only
      scattered single positive cells), and was only focal positive in two cases of
      CRCC. CD117 was expressed in 88% of ChRCC (28 of 32), 86% of renal oncocytoma (18
      of 21), and was negative in all CRCC (0 of 30). Twenty-six of the 30 cases of
      CRCC were positive (87%) for vimentin with prominent membrane staining patterns.
      All 23 chromophobe carcinomas were negative for vimentin and 15 of 21 oncocytomas
      demonstrated focal vimentin positivity, but less than 10%. The above results
      demonstrate that: (1) DOG1 was very sensitive and specific marker for distinguish
      ChRCC from CRCC; (2) Cyclin D1 was a useful marker to discriminate between ChRCC
      and renal oncocytoma; (3) CK7 and CD117 were useful markers to distinguish ChRCC
      from renal oncocytoma and CRCC. (4) Vimentin was helpful for distinguishing clear
      cell RCC from chromophobe and oncocytoma (87% of clear cell RCC positive,
      negative in chromophobe, only focally positive in oncocytoma). (5) CK8/18, CK19,
      CD10, beta-catenin and E-cadherin could not be used to distinguish ChRCC from
      renal oncocytoma and CRCC. 

PMID- 25596995
TI  - Multidisciplinary diagnostic approach combining fine needle aspiration, core
      needle biopsy and imaging features of a presacral myelolipoma in a patient with
      concurrent breast cancer.
AB  - Myelolipomas are uncommon benign tumors composed of mature adipose tissue mixed
      with hematopoietic elements; these tumors can occur in both the adrenal glands
      and extra-adrenal locations, the presacral region being the most frequent extra
      adrenal site. We present a case of presacral myelolipoma diagnosed by fine needle
      aspiration (FNA) and core needle biopsy (CNB) in a 55-year-old woman with
      concurrent invasive ductal breast cancer. TC and RM imaging were consistent with
      the diagnosis of presacral myelolipoma. The lesion was discovered incidentally
      during the staging procedure for breast malignancy. The purpose of our work is to
      describe the FNA and CNB finding in combination with the imaging features of this
      uncommon lesion. 

PMID- 25596996
TI  - PTEN expression in colorectal adenomas: relationship to morphology and cell
      heterogeneity.
AB  - INTRODUCTION: Colorectal adenomas are the most frequent benign colorectal tumors.
      These tumors are characterized by dysplasia, low and high grade, the latter
      having the potential to evolve to adenocarcinoma. The aim of this study was to
      study the expression patterns of PTEN protein in a series of colorectal adenomas
      and the relationships to cell proliferation and CD133, marker of stem phenotype.
      METHODS: Colorectal adenomas were studied for the immunohistochemical expression
      of PTEN on tissue microarrays. PTEN expression was analysed with regard to
      morphological features and with regard to the Ki67 and CD133-positive cell
      compartments by using the Kendall rank-correlation test. RESULTS: PTEN was
      expressed in 92% adenomas, either in a cytoplasmic or nuclear pattern.
      Cytoplasmic PTEN was correlated to cytoplasmic CD133 (p = 0.02, tau 0.191) while
      nuclear PTEN to decreased adenoma size and to tubular architecture (p = 0.01, tau
      0.184 and p = 0.01, tau-0.183). Nuclear PTEN was also correlated to low grade
      intraepithelial neoplasia, while global PTEN (nuclear or cytoplasmic) was
      correlated to the presence of a decreased Ki67-positive component but with
      marginal significance (p = 0.06, tau-0.144 and p = 0.07, tau-0.213). CONCLUSION:
      The results of this study suggest a role for PTEN in colorectal adenoma
      morphogenesis and cell protein heterogeneity, being correlated to decreased size,
      tubular architecture and a high CD133-positive component.

PMID- 25596998
TI  - Advanced imaging use in intensive care units has decreased, resulting in lower
      charges without negative effects on patient outcomes.
AB  - PURPOSE: There has been both greater recognition and scrutiny of the increased
      use of advanced imaging. Our aim was to determine whether there has been a change
      over time in the use of computed tomography (CT), magnetic resonance imaging
      (MRI), ultrasound (US) modalities in the intensive care units (ICUs). MATERIALS
      AND METHODS: A retrospective review of 75657 admissions to 20 ICUs was conducted.
      Results were analyzed with multivariate linear, negative binomial, and Poisson
      regressions. Primary outcomes were rates of use of CT, MRI, and US per 1000 ICU
      admissions every 6 months. Secondary outcomes were changes in radiology use
      associated with impacts on mortality, hospital length of stay (LOS), ICU LOS, and
      hospital charges. RESULTS: The rate of imaging use decreased by 13.5% between
      2007 and 2011 (incidence rate ratio [IRR], 0.982; P < .001). Most of this
      decrease was by CTs (21.0%; IRR, 0.973; P < .001). Use of MRI decreased by 6.0%
      (IRR, 0.991; P = .04), whereas US increased by 18.9% (IRR, 1.012; P < .001). The
      charges associated with imaging decreased by $74 per ICU admission, which would
      save an estimated $1.2 million in charges during 2011. Decreased imaging was not
      associated with changes in mortality, hospital, and ICU LOS. CONCLUSION: Advanced
      imaging use decreased for 5 years in the ICUs, resulting in decreased charges
      without negative effects on patient outcomes.

PMID- 25596997
TI  - Recurrent apocrine carcinoma of the scrotum: a case report.
AB  - Apocrine carcinoma is a rare tumor of the skin that typically arises in areas
      rich in apocrine glands, such as axilla and perineum. The main differential
      diagnosis is a metastasis from a primary apocrine carcinoma of the breast.
      Several authors have attempted to define morphological and immunohistochemical
      parameters to differentiate metastasis from primary apocrine carcinoma of the
      skin, but none of these had been demonstrated to be reliable markers. Here, we
      report a case of primary apocrine carcinoma of the scrotum that relapsed three
      times within a few years, without any clinical or radiological evidence of any
      other tumor of breast or other sites. 

PMID- 25596999
TI  - Full field spatially-variant image-based resolution modelling reconstruction for
      the HRRT.
AB  - Accurate characterisation of the scanner's point spread function across the
      entire field of view (FOV) is crucial in order to account for spatially dependent
      factors that degrade the resolution of the reconstructed images. The HRRT users'
      community resolution modelling reconstruction software includes a shift-invariant
      resolution kernel, which leads to transaxially non-uniform resolution in the
      reconstructed images. Unlike previous work to date in this field, this work is
      the first to model the spatially variant resolution across the entire FOV of the
      HRRT, which is the highest resolution human brain PET scanner in the world. In
      this paper we developed a spatially variant image-based resolution modelling
      reconstruction dedicated to the HRRT, using an experimentally measured shift
      variant resolution kernel. Previously, the system response was measured and
      characterised in detail across the entire FOV of the HRRT, using a printed point
      source array. The newly developed resolution modelling reconstruction was applied
      on measured phantom, as well as clinical data and was compared against the HRRT
      users' community resolution modelling reconstruction, which is currently in use.
      Results demonstrated improvements both in contrast and resolution recovery,
      particularly for regions close to the edges of the FOV, with almost uniform
      resolution recovery across the entire transverse FOV. In addition, because the
      newly measured resolution kernel is slightly broader with wider tails, compared
      to the deliberately conservative kernel employed in the HRRT users' community
      software, the reconstructed images appear to have not only improved contrast
      recovery (up to 20% for small regions), but also better noise characteristics. 

PMID- 25597000
TI  - [Enfermeria Clinica, going strong].

PMID- 25597001
TI  - [Native vitamin D in dialysis patients].
AB  - Chronic kidney disease is frequent and usually responsible of mineral and bone
      disorder. These abnormalities lead to increased morbidity and mortality. To
      become active, native vitamin D needs a first hydroxylation in the liver, and a
      second one in the kidney. Next to its action on bone metabolism, vitamin D also
      possesses pleiotropic actions on cardiovascular, immune and neurological systems
      as well as antineoplastic activities. End-stage renal disease (ESRD) is also
      associated with a decrease in vitamin D activity by mechanisms including the
      increase of plasma phosphate concentration, secretion of FGF-23 and decrease in
      1alpha-hydroxylase activity. The prevalence of 25 hydroxy-vitamin D deficiency
      depends on the chosen cut-off value to define this lack. Currently it is well
      established that a patient has to be substituted when 25 hydroxy-vitamin D level
      is under 30 ng/mL. The use and monitoring of 1.25 hydroxy-vitamin D is still not
      recommended in routine practice. The goals of vitamin D treatment in case of ESRD
      are to substitute the deficiency and to prevent or treat hyperparathyroidism.
      Interest of native vitamin D in first intention is now well demonstrated. This
      review article describes the vitamin D metabolism and physiology and also the
      treatment for vitamin D deficiency in ESRD population. 

PMID- 25597002
TI  - Pre-travel advice to the most immunocompromised; Trying to guide where evidence
      is scarce.

PMID- 25597003
TI  - Assessing the potential migration of people from Ebola affected West African
      countries to Latin America.

PMID- 25597004
TI  - Iminosugars as a new class of cholinesterase inhibitors.
AB  - To further extend the scope of iminosugar biological activity, a systematic
      structure-activity relationship investigation has been performed by synthesizing
      and evaluating as cholinesterase inhibitors a library of twenty-three
      iminoalditols with different substitutions and stereochemistry patterns. These
      compounds have been evaluated in vitro for the inhibition of cholinesterases
      (different sources of acetylcholinesterase and butyrylcholinesterase). Some
      compounds have IC50 values in the micromolar range and display significant
      inhibition selectivity for butyrylcholinesterase over acetylcholinesterase. These
      are the first examples of iminosugar-based inhibitors of cholinesterases. 

PMID- 25597005
TI  - The discovery of novel 3-(pyrazin-2-yl)-1H-indazoles as potent pan-Pim kinase
      inhibitors.
AB  - The three Pim kinases are a small family of serine/threonine kinases regulating
      several signaling pathways that are fundamental to tumorigenesis. As such, the
      Pim kinases are a very attractive target for pharmacological inhibition in cancer
      therapy. Herein, we describe our efforts toward the development of a potent, pan
      Pim inhibitor. The synthesis and hit-to-lead SAR development from a 3-(pyrazin-2
      yl)-1H-indazole derived hit 2 to the identification of a series of potent, pan
      Pim inhibitors such as 13o are described. 

PMID- 25597006
TI  - Discovery of thienoimidazole-based HCV NS5A inhibitors. Part 2: non-symmetric
      inhibitors with potent activity against genotype 1a and 1b.
AB  - The discovery of non-symmetric thienoimidazole-containing HCV NS5A inhibitors is
      described. The inhibitors herein reported display high potencies against both
      genotype 1a and 1b. In this follow-up manuscript, we discuss the importance of
      the linker aromaticity to achieve high potency, particularly against genotype 1a.

PMID- 25597007
TI  - Synthesis and pharmacological evaluation of multifunctional tacrine derivatives
      against several disease pathways of AD.
AB  - A novel series of tacrine derivatives were designed and synthesized by combining
      caffeic acid (CA), ferulic acid (FA) and lipoic acid (LA) with tacrine. The
      antioxidant study revealed that all the hybrids have much more antioxidant
      capacities compared to CA. Among these compounds, 1b possessed a good ability to
      inhibit the beta-amyloid protein (Abeta) self-aggregation, sub-micromole
      acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) inhibitory, modest
      BACE1 inhibitory. Moreover, compound 1b also was a DPPH radical scavenger and
      copper chelatory as well as had potent neuroprotective effects against glutamate
      induced cell death with low toxicity in HT22 cells. Our findings suggest that the
      compound 1b might be a promising lead multi-targeted ligand and worthy of further
      developing for the therapy of Alzheimer's disease. 

PMID- 25597008
TI  - Synthesis and properties of vitamin E analog-conjugated neomycin for delivery of
      RNAi drugs to liver cells.
AB  - RNA interference (RNAi) is a promising tool to regulate gene expression by
      external double stranded RNAs (dsRNAs) such as siRNAs. As an efficient method to
      deliver siRNAs to liver cells, we propose a novel strategy using vitamin E (VE)
      conjugated neomycin derivatives. With the aim of delivering RNAi-based drugs to
      liver cells, several tripod-type and prodrug-type neomycin derivatives were
      synthesized, all of which were thermodynamically stabilized RNA duplexes. The
      prodrug-type derivative 7 and the tripod-type derivative 10 were delivered to
      liver cancer cells and successfully induced RNAi activity. These results
      indicated the potential use of natural aminoglycosides as carriers of RNAi drugs.

PMID- 25597009
TI  - Synthesis and photophysical characterization of quasi push-pull
      dicyanodibenzodioxins and their anti-tumor activity against glioma cell line C6.
AB  - Dibenzodioxins bearing multiple electron withdrawing groups were synthesized
      using a simple one-step methodology including examples of molecules possessing
      electron acceptor groups in both ends. As a consequence internal charge
      delocalization occurs and the optical spectra are found to be bathochromically
      shifted compared to similar examples known thus far. A theoretical analysis of
      the molecular orbitals reveals the origin of the peaks in the dibenzodioxin
      optical spectra. Select examples exhibit in vitro neuro-cytotoxicity against
      glioma cell line C6, a finding which enhances existing knowledge about the
      pharmacologically relevant structural motifs in dibenzodioxins. 

PMID- 25597010
TI  - Multidrug resistance-reversal effects of resin glycosides from Dichondra repens.
AB  - Investigation of hydrophobic extract of Dichondra repens (Convolvulaceae) led to
      the isolation of three new resin glycosides dichondrins A-C (1-3), and three
      known resin glycosides cus-1, cus-2, and cuse 3. All the isolated resin
      glycosides with an acyclic core were evaluated for their multidrug resistance
      reversal activities, and the combined use of these compounds at a concentration
      of 25MUM increased the cytotoxicity of vincristine by 1.03-1.78-fold. 

PMID- 25597011
TI  - 6,6-Fused heterocyclic ureas as highly potent TRPV1 antagonists.
AB  - A series of N-[{2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-pyridin-3
      yl}methyl] N'-(6,6-fused heterocyclic) ureas have been investigated as hTRPV1
      antagonists. Among them, compound 15 showed highly potent TRPV1 antagonism to
      capsaicin, with Ki(ant)=0.2nM, as well as antagonism to other activators, and it
      was efficacious in a pain model. A docking study of 15 with our hTRPV1 homology
      model indicates that there is crucial hydrogen bonding between the ring nitrogen
      and the receptor, contributing to its potency. 

PMID- 25597013
TI  - [Right lower pulmonary lobe injury due to a Shaldon catheter].

PMID- 25597012
TI  - Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper
      methysticum and synthesis of analogs.
AB  - The ethanolic extract of the root of Piper methysticum was found to inhibit
      melanogenesis in MSH-activated B16 melanoma cells. Flavokawains B and C were
      isolated from this extract based on their anti-melanogenesis activity and found
      to inhibit melanogenesis with IC50 values of 7.7MUM and 6.9MUM, respectively.
      Flavokawain analogs were synthesized through a Claisen-Schmidt condensation of
      their corresponding acetophenones and benzaldehydes and were evaluated in terms
      of their tyrosinase inhibitory and anti-melanogenesis activities. Compound 1b was
      the most potent of these with an IC50 value of 2.3MUM in melanogenesis inhibition
      assays using MSH-activated B16 melanoma cells. 

PMID- 25597014
TI  - [Allergy to latex: The danger is in the warning].

PMID- 25597015
TI  - Transformation and time-out: the role of alcohol in identity construction among
      Scottish women in early midlife.
AB  - Despite the increase in drinking by women in early midlife, little alcohol
      research has focused on this group. We explore how alcohol is associated with the
      construction of gender identities among women aged 30-50 years in the west of
      Scotland, United Kingdom. We draw on qualitative data from 11 focus groups (five
      all-female, six mixed-sex) with pre-existing groups of friends and work
      colleagues in which women and men discuss their drinking behaviours. Analysis
      demonstrated how alcohol represented a time and space away from paid and unpaid
      work for women in a range of domestic circumstances, allowing them to relax and
      unwind. While women used alcohol to construct a range of identities, traditional
      notions of femininity remained salient (e.g. attention to appearance, drinking
      'girly' drinks). Drinking enabled women to assert their identity beyond the roles
      and responsibilities often associated with being a woman in early midlife. For
      example, some respondents with young children described the transformative
      effects of excessive drinking which allowed them to return temporarily to a
      younger, carefree version of themselves. Thus, our data suggest that women's
      drinking in early midlife revolves around notions of 'idealised' femininity but
      simultaneously represents a way of achieving 'time out' from traditional female
      responsibilities such as caring for others. We consider these findings within a
      broader social and cultural context including alcohol marketing, domestic roles
      and motherhood and their implications for health promotion. 

PMID- 25597016
TI  - Bioelectrical impedance phase angle relates to function, disease severity and
      prognosis in stable chronic obstructive pulmonary disease.
AB  - BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) provides a simple
      method to assess changes in body composition. Raw BIA variables such as phase
      angle provide direct information on cellular mass and integrity, without the
      assumptions inherent in estimating body compartments, e.g. fat-free mass (FFM).
      Phase angle is a strong functional and prognostic marker in many disease states,
      but data in COPD are lacking. Our aims were to describe the measurement of phase
      angle in patients with stable COPD and determine the construct and discriminate
      validity of phase angle by assessing its relationship with established markers of
      function, disease severity and prognosis. METHODS: 502 outpatients with stable
      COPD were studied. Phase angle and FFM by BIA, quadriceps strength (QMVC), 4-m
      gait speed (4MGS), 5 sit-to-stand time (5STS), incremental shuttle walk (ISW),
      and composite prognostic indices (ADO, iBODE) were measured. Patients were
      stratified into normal and low phase angle and FFM index. RESULTS: Phase angle
      correlated positively with FFM and functional outcomes (r = 0.35-0.66, p < 0.001)
      and negatively with prognostic indices (r = -0.35 to -0.48, p < 0.001). In
      regression models, phase angle was independently associated with ISW, ADO and
      iBODE whereas FFM was removed. One hundred and seventy patients (33.9% [95% CI,
      29.9-38.1]) had a low phase angle. Phenotypic characteristics included lower
      QMVC, ISW, and 4MGS, higher 5STS, ADO and iBODE scores, and more exacerbations
      and hospital days in past year. The proportion of patients to have died was
      significantly higher in patients with low phase angle compared to those with
      normal phase angle (8.2% versus 3.6%, p = 0.02). CONCLUSION: Phase angle relates
      to markers of function, disease severity and prognosis in patients with COPD. As
      a directly measured variable, phase angle offers more useful information than fat
      free mass indices.

PMID- 25597017
TI  - Limited miR-17-92 overexpression drives hematologic malignancies.
AB  - The overexpression of microRNA cluster miR-17-92 has been implicated in
      development of solid tumors and hematological malignancies. The role of miR-17-92
      in lymphomagenesis has been extensively investigated; however, because of the
      developmental defects caused by miR-17-92 dysregulation, its ability to drive
      tumorigenesis has remained undetermined until recently. Here we demonstrate that
      overexpression of miR-17-92 in a limited number of hematopoietic cells is
      sufficient to cause B cell malignancies. In sum, our study provides a novel and
      physiologically relevant model that exposes the potent ability of miR-17-92 to
      act as a driver of tumorigenesis. 

PMID- 25597019
TI  - Genitourinary Cancers Other than Prostate Cancer in a BRCA-tested Cohort from a
      Single Institution.

PMID- 25597018
TI  - Exome-wide Sequencing Shows Low Mutation Rates and Identifies Novel Mutated Genes
      in Seminomas.
AB  - BACKGROUND: Testicular germ cell tumors are the most common cancer diagnosed in
      young men, and seminomas are the most common type of these cancers. There have
      been no exome-wide examinations of genes mutated in seminomas or of overall rates
      of nonsilent somatic mutations in these tumors. OBJECTIVE: The objective was to
      analyze somatic mutations in seminomas to determine which genes are affected and
      to determine rates of nonsilent mutations. DESIGN, SETTING, AND PARTICIPANTS:
      Eight seminomas and matched normal samples were surgically obtained from eight
      patients. INTERVENTION: DNA was extracted from tissue samples and exome sequenced
      on massively parallel Illumina DNA sequencers. Single-nucleotide polymorphism
      chip-based copy number analysis was also performed to assess copy number
      alterations. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The DNA sequencing
      read data were analyzed to detect somatic mutations including single-nucleotide
      substitutions and short insertions and deletions. The detected mutations were
      validated by independent sequencing and further checked for subclonality. RESULTS
      AND LIMITATIONS: The rate of nonsynonymous somatic mutations averaged 0.31
      mutations/Mb. We detected nonsilent somatic mutations in 96 genes that were not
      previously known to be mutated in seminomas, of which some may be driver
      mutations. Many of the mutations appear to have been present in subclonal
      populations. In addition, two genes, KIT and KRAS, were affected in two tumors
      each with mutations that were previously observed in other cancers and are
      presumably oncogenic. CONCLUSIONS: Our study, the first report on exome
      sequencing of seminomas, detected somatic mutations in 96 new genes, several of
      which may be targetable drivers. Furthermore, our results show that seminoma
      mutation rates are five times higher than previously thought, but are
      nevertheless low compared to other common cancers. Similar low rates are seen in
      other cancers that also have excellent rates of remission achieved with
      chemotherapy. PATIENT SUMMARY: We examined the DNA sequences of seminomas, the
      most common type of testicular germ cell cancer. Our study identified 96 new
      genes in which mutations occurred during seminoma development, some of which
      might contribute to cancer development or progression. The study also showed that
      the rates of DNA mutations during seminoma development are higher than previously
      thought, but still lower than for other common solid-organ cancers. Such low
      rates are also observed among other cancers that, like seminomas, show excellent
      rates of disease remission after chemotherapy.

PMID- 25597020
TI  - A case of angiosarcoma arising from internal jugular vein.
AB  - Primary angiosarcoma is a rare disease with a poor prognosis. It most commonly
      arises in the head and neck region; localization in the deep soft tissue of the
      neck is extremely rare. We herein present a case of angiosarcoma derived from the
      right internal jugular vein. A 79-year-old man presented with a 1-month history
      of a growing right neck mass. Computed tomography, magnetic resonance imaging,
      positron emission tomography-computed tomography, and fine-needle aspiration
      cytology revealed a malignant tumor of unknown origin. Right neck dissection was
      performed for both diagnosis and therapy. Immunostaining of the resected tumor
      cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2-40,
      which allowed for a definitive diagnosis of angiosarcoma. Postoperative
      radiotherapy (66Gy) was performed on the right neck, including the surgical bed
      and upper mediastinum. The patient was followed up for 10 months with no
      recurrence. Only six cases of angiosarcoma arising in the deep soft tissue of the
      neck have been reported in the English-language literature. The present report is
      the first to describe angiosarcoma arising from the internal jugular vein. 

PMID- 25597021
TI  - Pure red cell aplasia due to anti-erythropoietin antibodies or isoniazid? A case
      report from a 94-year-old man.

PMID- 25597022
TI  - Extent of late gadolinium enhancement at right ventricular insertion points in
      patients with hypertrophic cardiomyopathy: relation with diastolic dysfunction.
AB  - OBJECTIVES: Our aim was to examine the association between the extent of late
      gadolinium enhancement (LGE) at right ventricular insertion points (RVIP) and
      left ventricular (LV) functional parameters in patients with hypertrophic
      cardiomyopathy (HCM). METHODS: Sixty-one HCM patients underwent echocardiography
      and cardiovascular magnetic resonance (CMR) within one week. Mitral annular
      velocities (E/E') were obtained from echocardiography; LV ejection fraction (EF),
      LV mass index, LV wall maximal thickness, and left atrial volume index (LAVI)
      were obtained from MR. LGE extent was quantified (proportion of total LV
      myocardial mass) according to location: % RVIP-LGE and % non-RVIP-LGE. RESULTS:
      Although LGE was commonly present in both apical (74 %) and non-apical HCMs (88
      %) (p = 0.163), RVIP-LGE was more frequent (86 % vs. 47 %, p = 0.002) in non
      apical HCMs in which E/E' was significantly higher (19.23 +/- 8.40 vs. 13.13 +/-
      5.06, p = 0.009). In addition, RVIP-LGE extent was associated with LV diastolic
      dysfunction (r = 0.45, p < 0.001 for E/E'; r = 0.53, p < 0.001 for LAVI) and
      lower LVEF (r = -0.42, p = 0.001). There was no correlation between non-RVIP-LGE
      extent and other parameters. Multiple linear regression analysis revealed RVIP
      LGE extent as an independent predictor of E/E' (beta = 0.45, p < 0.001) and LAVI
      in HCM patients (beta = 0.53, p < 0.001). CONCLUSIONS: The extent of LGE at RVIPs
      in HCM patients is associated with increased estimated LV filling pressure and
      chronic diastolic burden. KEY POINTS: * Late gadolinium enhancement at RV
      insertion points is frequently seen in HCM. * RVIP-LGE extent is correlated with
      increased estimated LV filling pressure in HCM. * Non-RVIP-LGE extent did not
      show any association with LV diastolic dysfunction.

PMID- 25597023
TI  - A reliable and economical method for gaining mouse embryonic fibroblasts capable
      of preparing feeder layers.
AB  - Mouse embryonic fibroblasts (MEFs) are widely used to prepare feeder layers for
      culturing embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)
      in vitro. Transportation lesions and exorbitant prices make the commercially
      obtained MEFs unsuitable for long term research. The aim of present study is to
      establish a method, which enables researchers to gain MEFs from mice and
      establish feeder layers by themselves in ordinary laboratories. MEFs were
      isolated from ICR mouse embryos at 12.5-17.5 day post-coitum (DPC) and cultured
      in vitro. At P2-P7, the cells were inactivated with mitomycin C or by X-ray
      irradiation. Then they were used to prepare feeder layers. The key factors of the
      whole protocol were analyzed to determine the optimal conditions for the method.
      The results revealed MEFs isolated at 12.5-13.5 DPC, and cultured to P3 were the
      best choice for feeder preparation, those P2 and P4-P5 MEFs were also suitable
      for the purpose. The P3-P5 MEFs treated with 10 MUg/ml of mitomycin C for 3 h, or
      irradiated with X-ray at 1.5 Gy/min for 25 Gy were the most suitable feeder
      cells. Treating MEFs with 10 MUg/ml of mitomycin C for 2.5 h, 15 MUg/ml for 2.0
      h, or irradiating the cells with 20 Gy of X-ray at 2.0 Gy/min could all serve as
      alternative methods for P3-P4 cells. Our study provides a reliable and economical
      way to obtain large amount of qualified MEFs for long term research of ESCs or
      iPSCs. 

PMID- 25597024
TI  - [Influence of body mass index on self-esteem of children aged 12-14 years].
AB  - INTRODUCTION: During the last decades, the increase in the rate of children and
      adolescents that are overweight or obese is alarming and it is related with a
      lower social competency, and low self-esteem. METHOD: A transversal study was
      conducted with a representative sample of 292 students enrolled in years 8 and 9
      at secondary school (13.05+/-0.97 years) in the city of Jaen, Spain. RESULTS:
      Girls wanted a thinner figure than boys (P < .001). Regarding self-esteem we
      observed statistically lower values in the case of girls (P < .000) as compared
      to their male counterparts. Regarding the BMI, students with a healthy weight
      have a statistically higher self-esteem score than students that are overweight
      and these have a slightly higher score than those that are obese. Positive
      correlation exists between the perceived silhouette and the desired silhouette
      (r=.485) and a negative correlation between the BMI and self-esteem (r=-.248).
      CONCLUSION: It is necessary to plan actions aimed as reinforcing and increasing
      self-esteem, focusing on the group of girls and the group of young adults with
      overweight and obesity problems.

PMID- 25597025
TI  - Reflections on empathy in medical education: What can we learn from social
      neurosciences?
AB  - The role of empathy in human social interaction has been examined in several
      research fields, including medical education (ME) and social neuroscience (SN).
      SN yields insights into empathy based on neurobiological processes, and such
      information may also be relevant to ME. In this reflection article, the authors
      first critically review current definitions and concepts of empathy in ME and
      link them to recent SN findings. In the light of recent evidence from SN,
      research in ME regarding the positive and negative effects of empathy for
      physicians and patients is discussed, as well as the question whether (future)
      physicians differ from the general population with regard to empathic skills.
      Commonly used SN paradigms and ME approaches to assess empathy are contrasted, a
      joint approach is advocated, and implications for further interdisciplinary
      studies are outlined. Finally, the authors delineate the contribution of SN to
      the question of whether empathy is teachable, and argue that SN findings
      represent a potential for new ME training approaches. In conclusion, the authors
      discuss how the incorporation of perspectives on empathy from different research
      areas would benefit ME, and suggest the translation and integration of such
      findings into ME research approaches. 

PMID- 25597026
TI  - Depression and vasomotor symptoms in young breast cancer survivors: the mediating
      role of sleep disturbance.
AB  - Depression, sleep disturbance, and vasomotor symptoms are common in breast cancer
      survivors (BCS), especially in younger women diagnosed before menopause. Risk
      factors and mechanisms for depression in this population are relatively
      unexplored. In 163 young BCS, vasomotor symptoms were significantly associated
      with higher depressive symptoms (beta = 0.26, p = 0.001) and 64 % of the total
      effect was mediated through sleep disturbance (beta for specific indirect effect
      = 1.296, 95 % CI 0.591-2.212). Treatments reducing vasomotor symptoms might
      alleviate sleep disturbance and depression in this population. 

PMID- 25597027
TI  - Echocardiography in cardiac amyloidosis.
AB  - Echocardiography is the most widely used noninvasive test in patients with heart
      failure or abnormal cardiac findings on examination. Patients with amyloidosis
      may have significant cardiac abnormalities, several of which are highly
      suggestive of the disease. This article reviews echocardiographic features found
      in cardiac amyloidosis. 

PMID- 25597028
TI  - Functions, Consequences, and Frequency of Non-suicidal Self-Injury.
AB  - We examined the correspondence between reported reasons and consequences for a
      specific act of non-suicidal self-injury (NSSI), and their relationship with
      lifetime NSSI frequency. College students with a history of NSSI (n = 52)
      indicated reasons for and consequences from their most recent NSSI episode. A
      match was coded when a reason and its corresponding consequence(s) were both
      endorsed by the participant. Reasons and consequences were significantly
      correlated, but their correspondence was not related to lifetime NSSI frequency.
      Automatic negative reasons explained lifetime NSSI frequency, but consequences
      and match between reasons and consequences did not. Reported reasons for NSSI may
      be more important in understanding maintenance of NSSI than either consequences
      or match.

PMID- 25597029
TI  - Insight Across the Different Mood States of Bipolar Disorder.
AB  - In bipolar disorder, levels of insight vary as a function of the mood state and
      appear to influence pharmacology compliance, quality of life, the presence of
      suicidal ideations, and aggressive behavior. To establish a comparison among
      different mood states in bipolar with regard to level of insight. Forty-eight
      patients were evaluated in different affective states (i.e., euthymia, mania,
      depression, and mixed state). Identifying information, sociodemographic data, and
      clinical records were recorded. The following scales were applied: Hamilton
      Depression Scale, Young Mania Rating Scale, Positive and Negative Syndrome Scale
      positive symptoms subscale, and Global Assessment of Functioning and Clinical
      Global Impressions Scale for use in bipolar disorder. Insight was evaluated using
      items 11 and 17 of the Young Mania Rating Scale and Hamilton Depression Scale,
      respectively. Insight in bipolar disorder was found to be more compromised during
      manic phases and mixed episodes than during periods of depression or euthymia.
      The factors associated with lower levels of insight were the following: shorter
      illness duration, older age, and greater severity in mania; the female gender and
      older age in depression; and shorter illness duration and more severe depressive
      symptoms in mixed episodes. In the same individual, levels of insight vary as a
      function of the affective state over the course of bipolar disorder and appear to
      be influenced by several clinical variables. 

PMID- 25597030
TI  - 12-Month Outcome and Predictors of Recurrence in Psychiatric Treatment of
      Depression: A Retrospective Study.
AB  - Many individuals treated for depression suffer relapse or recurrence after
      treatment. Known risk factors include number of previous depressive episodes and
      residual symptoms after treatment. Both relapse/recurrence rates and predictors
      of relapse/recurrence, however, may differ between various settings. To perform a
      naturalistic evaluation of the sustained effectiveness of treatment for adult
      clinical depression in a psychiatric out-patient setting and to examine
      psychosocial and clinical predictors of relapse/recurrence. 51 individuals, who
      were successfully treated/discharged from psychiatric care 12 months prior, were
      assessed regarding current depressive status and regarding relapse and
      recurrence. Logistic regression was used to assess the predictive impact of the
      variables measured. At the 12-month follow-up, 26% of the participants were in
      complete remission, 45% were in partial remission, and 29% were clinically
      depressed. In 1 year, 61% suffered a new depressive episode. Having a greater
      number of previous episodes and having no partner significantly increased the
      risk of relapse or recurrence. A high prevalence of depression and partially
      remitted depression is reported at 12-month follow up, and a large proportion of
      the sample would likely benefit from active treatment. Relapse/recurrence rates
      are higher in this study than in many other studies, and it may be hypothesized
      that they are generally higher in psychiatric settings than in primary care. If
      so, this would indicate the need for a different treatment strategy in the
      psychiatric care of depression, with emphasis on long-term management of
      depression.

PMID- 25597033
TI  - Clothing resultant thermal insulation determined on a movable thermal manikin.
      Part I: effects of wind and body movement on total insulation.
AB  - In this serial study, 486 thermal manikin tests were carried out to examine the
      effects of air velocity and walking speed on both total and local clothing
      thermal insulations. Seventeen clothing ensembles with different layers (i.e.,
      one, two, or three layers) were selected for the study. Three different wind
      speeds (0.15, 1.55, 4.0 m/s) and three levels of walking speed (0, 0.75, 1.2 m/s)
      were chosen. Thus, there are totally nine different testing conditions. The
      clothing total insulation and local clothing insulation at different body parts
      under those nine conditions were determined. In part I, empirical equations for
      estimating total resultant clothing insulation as a function of the static
      thermal insulation, relative air velocity, and walking speed were developed. In
      part II, the local thermal insulation of various garments was analyzed and
      correction equations on local resultant insulation for each body part were
      developed. This study provides critical database for potential applications in
      thermal comfort study, modeling of human thermal strain, and functional clothing
      design and engineering.

PMID- 25597032
TI  - Economic status and temperature-related mortality in Asia.
AB  - In developed countries, low latitude and high temperature are positively
      associated with the population's ability to adapt to heat. However, few studies
      have examined the effect of economic status on the relationship between long-term
      exposure to high temperature and health. We compared heterogeneous temperature
      related mortality effects relative to the average summer temperature in high
      socioeconomic-status (SES) cities to temperature-related effects in low-SES
      cities. In the first stage of the research, we conducted a linear regression
      analysis to quantify the mortality effects of high temperature (at or above the
      95th percentile) in 32 cities in Taiwan, China, Japan, and Korea. In the second
      stage, we used a meta-regression to examine the association between mortality
      risk with average summer temperature and gross domestic product (GDP) per capita.
      In cities with a low GDP per capita (less than 20,000 USD), the effects of
      temperature were detrimental to the population if the long-term average summer
      temperature was high. In contrast, in cities with a high GDP per capita,
      temperature-related mortality risk was not significantly related to average
      summer temperature. The relationship between long-term average summer temperature
      and the short-term effects of high temperatures differed based on the city-level
      economic status.

PMID- 25597035
TI  - Primary debulking surgery and neoadjuvant chemotherapy in the treatment of
      advanced epithelial ovarian carcinoma.
AB  - Surgery and chemotherapy are the standard of care for epithelial ovarian cancer,
      and it is well established that survival outcomes are improved when the surgery
      results in no or optimal (less than 1 cm) residual disease. However, for patients
      with bulky disease that may require extensive or radical procedures to accomplish
      this goal, the use of neoadjuvant chemotherapy followed by interval debulking
      surgery to simplify the surgery and minimize morbidity has been suggested.
      Arguably, this is only ideal if this process produces survival outcomes
      equivalent to those of primary debulking surgery. The purpose of this article is
      to review the data surrounding this controversial topic. 

PMID- 25597034
TI  - Antibiotic efficacy in patients with a moderate probability of acute
      rhinosinusitis: a systematic review.
AB  - The aim of this systematic review was to synthesize the results of original
      studies assessing antibiotic efficacy at different time points after initiating
      treatment in patients with a moderate probability of acute bacterial
      rhinosinusitis. We searched the Cochrane library for systematic reviews on the
      efficacy of antibiotic treatment in patients with acute rhinosinusitis (ARS).
      Only randomized controlled trials (RCTs) that compared treatment of any
      antibiotic with placebo were included. The synthesis of the results of six RCTs
      showed a benefit of antibiotic treatment compared to placebo for the rate of
      improvement after 3 [pooled odds ratio (OR) 2.78 (95 % confidence interval (CI)
      1.39-5.58)] and 7 [OR 2.29 (95 % CI 1.19-4.41)] days after initiation in patients
      with symptoms and signs of ARS lasting for 7 or more days. After 10 days [pooled
      OR 1.36 (95 % CI 0.66-2.90)], improvement rates did not differ significantly
      between patients treated with or without antibiotics. Compared to placebo,
      antibiotic treatment relieves symptoms in a significantly higher proportion of
      patients within the first days of treatment. Reporting an overall average
      treatment efficacy may underestimate treatment benefits in patients with a self
      limiting illness.

PMID- 25597036
TI  - The researcher as experimental subject: using self-experimentation to access
      experiences, understand social phenomena, and stimulate reflexivity.
AB  - The current article argues that researcher-as-subject self-experimentation can
      provide valuable insight and systematic knowledge to social psychologists. This
      approach, the modus operandi of experimental psychology when the field was in its
      infancy, has been largely eclipsed by an almost exclusive focus on participant-as
      subject other-experimentation. Drawing from the non-experimental first-person
      traditions of autoethnography, participant observation, and phenomenology, we
      argue that participating as both observer and subject within one's own social
      psychological experiment affords researchers at least three potential benefits:
      (1) access to "social qualia," that is, the subjective experience of social
      phenomena; (2) improved mental models of social phenomena, potentially
      stimulating new research questions; and (3) an enhanced ability to be reflexive
      about the given experiment. To support our position, we provide first-person self
      reflections from researchers who have self-experimented with transformed social
      interactions involving Milgram's cyranoid method. We close by offering guidelines
      on how one might approach self-experimentation, and discuss a variety of first
      person perspective ethnographic technologies that can be incorporated into the
      practice. 

PMID- 25597037
TI  - Fast periodic presentation of natural images reveals a robust face-selective
      electrophysiological response in the human brain.
AB  - We designed a fast periodic visual stimulation approach to identify an objective
      signature of face categorization incorporating both visual discrimination (from
      nonface objects) and generalization (across widely variable face exemplars).
      Scalp electroencephalographic (EEG) data were recorded in 12 human observers
      viewing natural images of objects at a rapid frequency of 5.88 images/s for 60 s.
      Natural images of faces were interleaved every five stimuli, i.e., at 1.18 Hz
      (5.88/5). Face categorization was indexed by a high signal-to-noise ratio
      response, specifically at an oddball face stimulation frequency of 1.18 Hz and
      its harmonics. This face-selective periodic EEG response was highly significant
      for every participant, even for a single 60-s sequence, and was generally
      localized over the right occipitotemporal cortex. The periodicity constraint and
      the large selection of stimuli ensured that this selective response to natural
      face images was free of low-level visual confounds, as confirmed by the absence
      of any oddball response for phase-scrambled stimuli. Without any subtraction
      procedure, time-domain analysis revealed a sequence of differential face
      selective EEG components between 120 and 400 ms after oddball face image onset,
      progressing from medial occipital (P1-faces) to occipitotemporal (N1-faces) and
      anterior temporal (P2-faces) regions. Overall, this fast periodic visual
      stimulation approach provides a direct signature of natural face categorization
      and opens an avenue for efficiently measuring categorization responses of complex
      visual stimuli in the human brain. 

PMID- 25597039
TI  - DSM-5 schizoaffective disorder: will clinical utility be enhanced?

PMID- 25597038
TI  - The association between type and number of adverse working conditions and mental
      health during a time of economic crisis (2010-2012).
AB  - PURPOSE: Many studies have been published on the association between adverse
      psychosocial working conditions and mental health, but only a few related types
      of adverse job conditions and a count of these adversities to workers' mental
      health, using standardized diagnostic interviews. This study addresses this
      issue. METHODS: Data were used from the second wave of the Netherlands Mental
      Health Survey and Incidence Study-2, a nationally representative face-to-face
      survey of the general population, including 3,672 workers, 166 unemployed and 239
      disabled persons. Among workers, psychosocial working conditions (decision
      latitude, psychological job demands, job security and co-worker support) were
      assessed with the Job Content Questionnaire. Mental health symptoms were assessed
      with the Mental Health Inventory (MHI)-5 and DSM-IV diagnoses/syndromes with the
      Composite International Diagnostic Interview 3.0. RESULTS: Adverse psychosocial
      job conditions were related to workers' mental health. The strongest association
      was found for low job security which increased the chance of mental health
      symptoms and mental disorders by twofold. Workers in the poorest quality jobs,
      i.e. experiencing at least three adverse working conditions, had a 3 to almost 5
      times higher chance of mental disorders than those in the most optimal jobs.
      Having a poor quality job was not associated with better mental health compared
      to being unemployed or disabled. In general, similar relations were found for
      mood, anxiety and substance use disorders. CONCLUSIONS: In planning future
      strategies to prevent mental disorders at the workplace, the focus should be on
      workers who experience job insecurity and on those who report several
      adversities.

PMID- 25597031
TI  - Insights into the genetic foundations of human communication.
AB  - The human capacity to acquire sophisticated language is unmatched in the animal
      kingdom. Despite the discontinuity in communicative abilities between humans and
      other primates, language is built on ancient genetic foundations, which are being
      illuminated by comparative genomics. The genetic architecture of the language
      faculty is also being uncovered by research into neurodevelopmental disorders
      that disrupt the normally effortless process of language acquisition. In this
      article, we discuss the strategies that researchers are using to reveal genetic
      factors contributing to communicative abilities, and review progress in
      identifying the relevant genes and genetic variants. The first gene directly
      implicated in a speech and language disorder was FOXP2. Using this gene as a case
      study, we illustrate how evidence from genetics, molecular cell biology, animal
      models and human neuroimaging has converged to build a picture of the role of
      FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge
      the gaps between genes, brains and behavior. 

PMID- 25597041
TI  - The association between symptom severity and physical activity participation in
      people seeking care for acute low back pain.
AB  - PURPOSE: To investigate the association between symptom severity and physical
      activity participation in people with acute non-specific low back pain (LBP).
      METHODS: The sample included a total of 999 patients who presented to primary
      care with an acute episode of low back pain. Symptom severity, in terms of
      activity limitation and severity of pain; and physical activity participation
      before (habitual) and after pain onset were assessed using self-report
      questionnaires. All participants were interviewed within 14 days of pain onset.
      RESULTS: At interview most of the participants (87.5 %) reported having moderate
      to extreme activity limitation due to back pain. There was a significant decrease
      in physical activity participation after pain onset (mean difference: -176 min,
      95 % CI 327-400; p < 0.0001) but no association between habitual or change in
      physical activity participation and symptom severity was observed (p > 0.21).
      CONCLUSION: Pain onset causes a significant and immediate decrease in physical
      activity participation, but this change does not seem to be associated with
      symptom severity.

PMID- 25597040
TI  - Posterior vertebral column resection and intraoperative manual traction to
      correct severe post-tubercular rigid spinal deformities incurred during
      childhood: minimum 2-year follow-up.
AB  - PURPOSE: To evaluate the clinical and radiographic outcomes of posterior
      vertebral column resection (PVCR) and intraoperative manual traction to correct
      severe post-tubercular spinal deformity incurred during childhood. METHODS: A
      retrospective review of 11 patients' (4 males and 7 females) charts was
      performed. Clinical outcome assessment was performed using Oswestry Disability
      Index and Visual Analog Scale for back pain. Imaging measurements and fusion
      status were assessed using plain radiography and computed tomography.
      Intraoperative and postoperative complications were recorded. RESULTS: No
      perioperative mortality occurred among the patients. The average follow-up was
      42.8 +/- 13.1 months (range 25-60 months). Kyphosis improved from a preoperative
      average of 93.4 degrees  +/- 10.1 degrees  to a postoperative average of 18.7
      degrees  +/- 6.3 degrees  for a correction of 80.1 %. The Cobb angle in the
      coronal plane improved from an average of 48.1 degrees  +/- 18.9 degrees  to 10.3
      degrees  +/- 3.0 degrees  postoperatively for a correction of 76.3 %. At the last
      follow-up, two patients improved neurologically from ASIA grade C to grade D, and
      one patient improved from grade C to grade E. Only one patient with ASIA grade D
      deficits did not improve. Perioperative complications occurred in 4 of the 11
      cases. One patient had a dural tear. Three patients had temporary degradation of
      intraoperative neuromonitoring, and one experienced transient paralysis of the
      left lower extremity postoperatively. CONCLUSIONS: PVCR and intraoperative manual
      traction are effective alternatives to manage severe post-tubercular spinal
      deformity although the procedure can be highly challenging with possible
      neurologic complications.

PMID- 25597043
TI  - Energy transfer studies between Trp residues of three lipocalin proteins family,
      alpha1-acid glycoprotein, (orosomucoid), beta-lactoglobulin and porcine odorant
      binding protein and the fluorescent probe, 1-aminoanthracene (1-AMA).
AB  - Energy transfer studies between Trp residues of alpha(1)-acid glycoprotein, beta
      lactoglobulin and porcine odorant binding protein (OBP) and the fluorescent probe
      1-aminoanthracene (1-AMA) were performed. 1-AMA binds to the hydrophobic binding
      sites of the three proteins inducing a decrease in the fluorescence intensity of
      the Trp residues accompanied by an increase of that of 1-AMA. Our results
      indicate that 1-AMA is in close contact with hydrophobic tryptophan residue of
      beta-lactoglobulin (Trp 19) to the difference of its binding to OBP, where Trp
      residues are far from the pocket and to alpha(1)-acid glycoprotein where three
      Trp residues are present at different areas of the protein.

PMID- 25597042
TI  - The ethics of deep brain stimulation (DBS).
AB  - Deep brain stimulation (DBS) is an invasive technique designed to stimulate
      certain deep brain regions for therapeutic purposes and is currently used mainly
      in patients with neurodegenerative disorders, such as Parkinson's disease.
      However, DBS is also used increasingly for other experimental applications, such
      as the treatment of psychiatric disorders (e.g. severe depression), weight
      reduction. Apart from its therapeutic potential, DBS can cause severe adverse
      effects, some that might also have a significant impact on the patient's
      personality and autonomy by the external stimulation of DBS which effects lie
      beyond the individual's control and free will. The article's purpose is to
      outline the procedures of DBS currently used in therapeutic and experimental
      applications and to discuss the ethical concerns regarding this procedure. It
      will address the clinical benefit-risk-ratio, the particular ethics of research
      in this field, and the ethical issues raised by affecting a patient's or an
      individual's personality and autonomous behaviour. Moreover, a potential ethical
      guideline, the Ulysses contract is discussed for the field of clinical
      application as well as the question of responsibility. 

PMID- 25597045
TI  - Identification of natural indigo in historical textiles by GC-MS.
AB  - The possibility of successfully applying a common GC-MS procedure for
      identification in one step of all types of dyes from plants of unknown origin and
      from historical objects is particularly attractive due to the high separation
      efficiency of the capillary columns, the MS detection sensitivity and the
      reproducibility of results. In this work, GC-MS analysis, previously and
      successfully used for the characterization of anthraquinones, flavonoids and
      tannins from plant extracts and historical samples, has been tested on indigoid
      dyestuffs. An analytical procedure based on the silylating agent N,O-bis
      (trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS)
      was applied to pure molecules of indigotin and indirubin and to plant extracts of
      Indigofera tinctoria L. and Isatis tinctoria L. Preliminary tests have been done
      to establish the chromatographic conditions and the derivatization amounts most
      suitable for the simultaneous detection of indigoid molecules and of the other
      natural compounds, such as fatty acids, carboxylic acids and sugars, contained
      within the plant extracts. In order to assess the capacity and the sensitivity of
      the analytical procedure in typical archaeometric applications, wool samples dyed
      in the laboratory with indigo were analysed by mimicking the sample amounts
      typically available with historical objects. The electron ionization (EI) spectra
      of the main silylated derivatives of indigoid molecules obtained in this way
      constitute the necessary data set for the characterization of natural extracts
      and historical works of art. Subsequently, the procedure has been applied to
      historical samples for the detection of indigo and of other dyestuffs eventually
      contained in samples. Additional information, useful for restoration and
      preservation of works of art, could be also obtained on the nature of stains and
      smudges present on the sampled textile material. The GC-MS method turns out to be
      an efficient and fast analytical tool also for the identification of natural
      indigo in plants and textile artefacts, providing results complementary to those
      from high-performance liquid chromatography (HPLC).

PMID- 25597044
TI  - A dansyl-rhodamine ratiometric fluorescent probe for Hg2+ based on FRET
      mechanism.
AB  - Based on resonance energy transfer (FRET) from dansyl to rhodamine 101, a new
      fluorescent probe (compound 1) containing rhodamine 101 and a dansyl unit was
      synthesized for detecting Hg(2+) through ratiometric sensing in DMSO aqueous
      solutions. This probe shows a fast, reversible and selective response toward
      Hg(2+) in a wide pH range. Hg(2+) induced ring-opening reactions of the
      spirolactam rhodamine moiety of 1, leading to the formation of fluorescent
      derivatives that can serve as the FRET acceptors. Very large stokes shift (220
      nm) was observed in this case. About 97-fold increase in fluorescence intensity
      ratio was observed upon its binding with Hg(2+). 

PMID- 25597046
TI  - Direct determination of major components in human diets and baby foods.
AB  - A fast method has been developed for the determination of fat, proteins,
      carbohydrates, and energy value in baby food, infant fast food, and canteen
      menus, using near-infrared (NIR) and mid-infrared (MIR) spectroscopy measurements
      and multivariate calibration methods based on partial least square regression.
      Reference standard methods were employed to build and validate the infrared
      methods for direct determination of nutrients. Coefficients of determination
      obtained between predicted values and reference ones for total fat, proteins,
      carbohydrates, and energy value were 96.7, 98.1, 98.9, and 96.5 for NIR and 91.0,
      93.0, 92.0, and 84.1 for MIR, respectively, with relative root mean square error
      of prediction (RRMSEP) below or equal to 9 % for NIR and 16 % for MIR. Results
      obtained indicate that both NIR and MIR techniques have good predictive
      capabilities, with the NIR method being the most accurate and simple. 

PMID- 25597047
TI  - Osteoskeletal manifestations of scurvy: MRI and ultrasound findings.
AB  - Scurvy has become very rare in the modern world. The incidence of scurvy in the
      pediatric population is extremely low. In the pediatric population,
      musculoskeletal manifestations are more common and multiple subperiosteal
      hematomas are an important indicator for the diagnosis of scurvy. Although
      magnetic resonance imaging findings of scurvy are well described in the
      literature, to our knowledge, ultrasound findings have not yet been described. In
      this article, we report a case of scurvy with associated magnetic resonance
      imaging and ultrasound findings. 

PMID- 25597048
TI  - Franciszek Walter (1885-1950) and a non-American concept of the origin of
      syphilis in Europe.
AB  - The start of Polish dermatology began in the second half of the 19th century with
      the development of this field of medicine. Initially, this occurred in larger
      academic centers, which at that time included Krakow, Warsaw, Poznan, Vilnius,
      and Lvov. The first University Department of Dermatology in Poland was
      established in 1863 at the Jagiellonian University in Krakow, with its first
      director being Anthony Rosner, followed by among others Wladyslaw Reiss and Jan
      Lenartowicz, but the most important member would be Franciszek Walter.

PMID- 25597049
TI  - [Molecular targeted therapy].

PMID- 25597050
TI  - Detection of influenza virus  subtype A by polymerase chain  reaction: WHO
      external quality  assessment programme  summary analysis, 2014.

PMID- 25597051
TI  - RP first look: new recommended practices for cleaning and care of surgical
      instruments.

PMID- 25597052
TI  - Implementing evidence-based care for   patients with obstructive sleep apnea.

PMID- 25597054
TI  - [The smells of long ago evoke images and memories].

PMID- 25597053
TI  - Best practices: improving patient outcomes and costs in an ACO through
      comprehensive medication therapy management.
AB  - BACKGROUND: One of the most important and often overlooked challenges for
      accountable care organizations (ACOs) is ensuring the optimal use of
      pharmaceuticals, which can be accomplished by utilizing pharmacists' skillsets
      and leveraging their full clinical expertise. Developing capabilities that
      support, monitor, and ensure appropriate medication use, efficacy, and safety is
      critical to achieving optimal patient outcomes and, ultimately, to an ACO's
      success. The program described in this article highlights the best practices of
      Fairview Pharmacy Services' Medication Therapy Management (MTM) program with
      additional thoughts and considerations on this and similar MTM programs provided
      by The Working Group on Optimizing Medication Therapy in Value-Based Healthcare.
      PROGRAM DESCRIPTION: Fairview Pharmacy Services utilizes 23 MTM pharmacists
      (approximately 18 full-time equivalents) working in 30 locations, who conduct
      pharmacotherapy workups as part of the MTM services that Fairview provides.
      Pharmacists focus on patients in a comprehensive manner and assess all of their
      diseases and medications. Responsibilities include (a) identification of a
      patient's drug-related needs with a commitment to meet those needs; (b) an
      assessment and confirmation that all of a patient's drug therapy is appropriately
      indicated, effective and safe, and that the patient is compliant; (c) achievement
      of therapy outcomes and ensuring documentation of those outcomes; and (d)
      collaboration with all members of a patient's care team. OBSERVATIONS: Since
      1998, pharmacists have cared for more than 20,000 patients and resolved more than
      107,000 medication-related problems which, if left unresolved, could have led to
      hospital readmissions and emergency visits. Since becoming a Pioneer ACO,
      Fairview pharmacists have focused on the highest-risk members and have seen over
      670 ACO patients, resolving over 2,780 medication-related problems. In terms of
      clinical outcomes, MTM contributed to optimal care in complex patients with
      diabetes. A review of 2007 data found that the percentage of diabetes patients
      optimally managed (as measured by a composite of hemoglobin A1c, low-density
      lipoprotein, blood pressure, aspirin use, and no smoking) was significantly
      higher for MTM patients (21% vs. 45%, P < 0.01). The Fairview MTM also showed a
      12:1 return on investment (ROI) when comparing the overall health care costs of
      patients receiving MTM services with patients who did not receive those services.
      IMPLICATIONS: Developing an MTM program to manage and optimize pharmaceuticals
      will be a cornerstone to managing the health of a population. Important lessons
      have been learned that may be helpful to other health systems developing MTM
      programs. In an accountable care environment measuring the return on the
      investment of all care interventions, including MTM will be essential to maintain
      the program. The ACO will also have to be able to correctly identify which
      patients are candidates for MTM services and provide pharmacists with enough
      autonomy, including scheduling face-to-face interactions with patients and the
      ability to change prescriptions if necessary, to ensure that timely and effective
      care is delivered. In order for an ACO to deliver high quality patient-centered
      medication services, there must be clear lines of communication between
      providers, pharmacists, and the other care providers within the organization.
      Finally, a strong and visionary leader is critical to ensuring the success of an
      MTM program and ultimately the ACO itself. RECOMMENDATIONS: While there is a
      plethora of literature touting the benefits of either in-person or telephonic
      based MTM, there is little research to date that directly compares these 2 MTM
      delivery types. It is critical for research to address the direct and indirect
      costs associated with starting and maintaining an MTM program. Information such
      as technologies required to start a program and length of time until a program
      breaks even or meets a sufficient ROI can be helpful for health care providers in
      similar health systems pitching a similar type of program. Finally, there has yet
      to be significant empirical research into the cost savings of utilizing a
      pharmacist and MTM services associated with meeting quality and cost benchmarks
      in an accountable care payment arrangement.

PMID- 25597055
TI  - [The central region takes action for the elderly].

PMID- 25597056
TI  - [Nurses and the night shift].

PMID- 25597057
TI  - [Euthanasia increases in Belgium].

PMID- 25597058
TI  - [Serious adverse events related to primary care].

PMID- 25597059
TI  - [Taking a look at Alzheimer's].

PMID- 25597060
TI  - [Antipsychotics and dementia].

PMID- 25597061
TI  - [Benzodiazepines and risk of Alzheimer's].

PMID- 25597062
TI  - [The end of life and the elderly, a nursing act in itself].

PMID- 25597063
TI  - [The places of death of people aged 80 and over in France].
AB  - While the places and causes of death are the subject of abundant literature, the
      circumstances surrounding the end of life, the ultimate phase of existence,
      remain largely not explored in France. The pathways through different living
      places taken by people aged 80 and over during the last month of existence and
      the factors associated with them are described thanks to the unique information
      and data collected by the "End of Life in France" survey.

PMID- 25597064
TI  - [Anticipating the end of life].
AB  - For patients at the end of life, caregivers must sometimes make choices between
      prolonging life and quality of life. There are several tools to assist in the
      decision-making process and the implementation, notably with regard to the
      limiting of active treatment. The issues to consider include limiting or stopping
      treatment, Leonetti's law with advance directives and the fight against
      unreasonable obstinacy and, more recently, the "mandate for future protection".
      The patient must always remain the focus and be allowed to express their wishes,
      if they want to, directly or with the help of a third party.

PMID- 25597065
TI  - [The role and specificity of palliative care networks in geriatrics].
AB  - The treatment of patients in palliative care is complex, and must be global and
      multi-disciplinary. With elderly patients, several elements can further
      complicate the situation: comorbidities, cognitive disorders, isolation, etc.
      Palliative care networks have a role to play in providing specialised expertise
      and coordination. They contribute to enabling patients to remain at home in good
      conditions, assist doctors with regard to specific strategies (pain and other
      difficult symptoms), assure a link between the different community and hospital
      professionals, anticipate potential problems and help to limit hospital
      admissions via emergency departments.

PMID- 25597066
TI  - [The end of life in a long-term care unit].
AB  - Following the principles of Leonetti's Law and to improve practices in long-term
      care units, caregivers decided to create a decision aid to help in the process to
      determine whether to limit care, adapted to the profile of the unit's residents.
      The aid is the fruit of a collective and ethical approach which helps caregivers
      decide on the action to take in the event of an acute crisis and enables the
      patient to express their wishes concerning the end of life.

PMID- 25597067
TI  - [A sheet for deciphering the cries of hospitalized elderly patients].
AB  - Crying out is not an insignificant act and it is important to fight against this
      misconception. Any caregiver can be confronted with this phenomenon with elderly
      hospitalised patients. Their cries must be understood, analysed and taken into
      account as they correspond to a particular situation experienced by the elderly
      patient. There are tools to help caregivers diagnose and reflect on this clinical
      context. This article presents the example of an interpretation sheet which can
      help caregivers decipher patients' cries.

PMID- 25597069
TI  - [Bibliography. End of life: course of action].

PMID- 25597068
TI  - [Advance instructions for patients at the end of life at home and the nurse's
      role].
AB  - An elderly person's choice to remain at home until the end of their life must be
      respected. Their care requires a multidisciplinary approach in consultation with
      the patient and their family. The fundamental element remains the support of a
      human being approaching the end of life. This article presents the example of the
      Arc en Ciel palliative care network which works with patients in their homes.

PMID- 25597070
TI  - [An instinctive psychodynamic approach of "free choice" for elderly people in
      nursing homes].
AB  - The free choice of the elderly is usually approached from a legal aspect. This
      approach sits easily within our democratic society. However, considering the
      issue solely from a legal standpoint means denying elderly people their
      psychological privacy, notably with regard to their capacity for self
      determination.

PMID- 25597071
TI  - [The duty to tell the truth with regard to a person with Alzheimer's disease].
AB  - In the framework of a project relating to ethical questioning, pupils in their
      penultimate year at Mabillon des Ardennes high school gathered testimonies which
      revealed that the truth is sometimes hidden from people with Alzheimer's disease.
      Why is this right to the truth not always respected? In what circumstances does
      it happen? What are the reasons? What are the potential consequences? Reflection
      is required around the question of the respect of the right to the truth for
      people with cognitive disorders.

PMID- 25597072
TI  - [Diagnosis and management of complex tuberculosis].

PMID- 25597073
TI  - [Urinary tract infections and pyelonephritis in the elderly].

PMID- 25597074
TI  - [Implementation of 3D heart modeling based on an improved region rowing method].
AB  - Image segmentation is a key step for image processing. This study developed an
      improved region growing algorithm to extract the outline of the heart for 3D
      modeling which based on the acquisition of canine cardiac CT images from animal
      experiment. In this paper the method was also compared with the classic algorithm
      of threshold segmentation. The result showed that the method can be used for the
      3D display technology of cardiac electrical activity in clinical
      electrophysiology mapping.

PMID- 25597075
TI  - [The application of Hilbert-Huang transform in speech coding algorithm for
      cochlear implants].
AB  - To enhance speech recognition in realistic listening environment, as well as
      tonal language and music perception, a new speech coding strategy based on
      Hilbert Huang transform was presented. Instantaneous frequency and instantaneous
      amplitude which reflect speech contents, speech rhythms and tones are derived
      from original speech signal through empirical mode decomposition and the Hilbert
      transform to synthesize stimulating pulses. The presented new speech coding
      algorithm, continuous interleaved sampling, and frequency amplitude modulation
      encoding strategies were simulated by Matlab and synthesized signals of 50
      Mandarin speech test materials are correlation analyzed between original signals.
      Compared to other two strategies, the presented new strategy obtains the highest
      correlation coefficient between synthesized signal and that of original speech,
      which indicates it could keep more information of the original speech signal than
      other two strategies.

PMID- 25597076
TI  - [Multi-channel motion signal acquisition system and experimental results].
AB  - For the study of muscle function and features during exercise, a multi-channel
      data acquisition system was developed, the overall design of the system, hardware
      composition, the function of system and so on have made a detail implements. The
      synchronous acquisition and storage of the surface EMG signal, joint angle
      signal, plantar pressure signal, ultrasonic image and initial results have been
      achieved.

PMID- 25597077
TI  - [Fluid solid interaction analysis of bioprosthetic heart valve].
AB  - This paper constructs numerical models of bioprosthetic heart valve and blood.
      The fluid solid interaction is carried out using penalty function method. The
      mechanical property of the bioprosthetic heart valve during cardiac cycle is
      simulated with ANSYS software. Results show that the Von Mises stress
      concentrates at the junction of attachment edge and coaptation edge. The open
      time of bioprosthetic heart valve is consistent with that of actural measurement.
      The peak velocity of blood is in the range of physiology. This model provides
      more realistic mechanical property of bioprosthetic heart valve during cardiac
      cycle compared to pure solid model, and facilitates design and optimization of
      bioprosthetic heart valve.

PMID- 25597079
TI  - [Design of portable pressure-pained-detector based on STM32].
AB  - In accordance with the bulky volume and not easy to carry of pain detection
      equipment limitations, designs a kind of portable high-precision dolorimeter
      based on STM32. Using the high precision pressure sensor pressure contact as the
      main body to make the pressure pain signals. Through the signal preprocess of the
      amplifying circuit and the filter circuit, to eliminate the system noise
      effectively. Use the TFT-LCD to display the real-time measured pressure value,
      and establish a pressure pain threshold of the object. The USB interface
      transmits the data to PC to store, and it's beneficial to the diagnosis and
      treatment of subsequent.

PMID- 25597078
TI  - [A wireless implantable stimulating and ECG monitoring system for animal models
      of chronic atrial fibrillation].
AB  - The rapid atrial pacing model is one of the most popular atrial fibrillation
      animal models. In this paper, a novel implementation of wireless implantable
      stimulating and ECG monitoring system is described based on the requirements of
      rapid atrial pacing model. Hardware circuits and software structure of the system
      are introduced. And test outcomes through in-vitro simulation and in-vivo animal
      models are presented. After verified by animal tests, the system can be used to
      initiate and monitor chronic atrial fibriation in real time.

PMID- 25597080
TI  - [Development of cardiac output monitoring system based on thermodilution method].
AB  - Cardiac output (CO) monitoring is a crucial part of the hemodynamic status
      monitoring. So far, thermodilution method, which is clinically recognized as the
      gold standard method to monitor cardiac output, still has irreplaceable
      advantages. This paper mainly introduces the use of platform for cardiac output
      measurement based on thermodilution method, mainly including three parts: the
      hardware platform, software design and algorithm process. A large amount of test
      data of this system has been got by CO simulator testing in the laboratory and
      preliminary clinical tests in the hospital. The testing result showed that using
      the proposed system can achieve good accuracy and repeatability.

PMID- 25597081
TI  - [The study of simulation system for cardiopulmonary bypass cardiac surgery].
AB  - According to the clinical requirements of cardiopulmonary bypass surgery, this
      paper established a simulation system for cardiac surgery which consists of
      venous reservoir, variable balance chamber, blood suction bag, ventricle suction
      bag, resistance valves, pressure gauges and tubings. Using the proposed system,
      perfusionists can mimic the implementation of pre-established surgery strategy,
      predict various abnormal conditions in the operation, and accordingly take the
      urgent actions so as to improve the success rate of surgery and to ensure the
      safety of patients.

PMID- 25597082
TI  - [Optimal design of portable ambulatory blood pressure monitor based on STM32L].
AB  - Based on the 32-bit ultra low power microcontroller STM32L151RBT6 using ARM
      Cortex-M3 kernel, the portable ambulatory blood pressure monitor powered by two
      AA batteries was designed. In order to insure the stability of power supply and
      prevent overpressure of cuff, super capacitor technology and new kind of safety
      logic circuits were used. The experimental result shows that: this solution is
      accurate and stable, which has high safety coefficient and a great clinical
      application value.

PMID- 25597083
TI  - [The research progress of transcatheter aortic valve replacement].
AB  - During the past years transcatheter aortic valve replacement has evolved to a
      promising technique for the treatment of the patients who suffered from severe
      aortic stenosis, the progress and basic consideration on clinical study have been
      summarized in the article.

PMID- 25597084
TI  - [International progress of unique device identification for medical devices].
AB  - Unique Device Identification (UDI) is a hot spot research area in the medical
      device administration. It comes a breakthrough from International Medical Device
      Regulators Forum (IMDRF) and government implementation recently. The article
      reviewed the advancement of IMDRF UDI program, discussed the framework for UDI
      system, analyzed the implementation of UDI in other countries, put forward some
      suggestions on the development of medical device coding system in our country.

PMID- 25597085
TI  - [Administrative reform thinking on the regulations on the supervision and
      administration of medical devices].
AB  - This paper learned and interpreted the regulations on the supervision and
      administration of medical devices, carded the thoughts of administrative reform,
      then put forward the "ten principles", including full supervision, classification
      supervision, risk classification, safety-effective-save, to encourage innovation,
      simplified license, scientific-standard, sincerity & self-discipline, clear
      responsibility, severe punishment, and discussed these priciples.

PMID- 25597086
TI  - [Analysis of the current situation of production supervision of medical devices
      in China].
AB  - The paper introduces supervision situation of enterprises of medical devices from
      the aspects of supervision team of medical devices, construction of credit system
      and implementation of regulation of quality management of medical devices, and
      raises supervision difficulties and puts forwards corresponding proposals.

PMID- 25597087
TI  - [Practice on the data normalization of medical device adverse event reporting and
      exploration on improving the quality of the reports].
AB  - On the basis of real working practices in data normalization, the case reports
      from the monitoring system were studied, non-standard reports were summarized and
      the reasons were analyzed, the methods of data normalization and improving the
      reporting quality were discussed. The standard databases and the rule databases
      were created, they were capable of automatic completion of the standardization
      work of new cases.

PMID- 25597088
TI  - [Reference the YY/T 0841-2011 standard to improve preventive maintenance of
      medical electrical equipment and experience].
AB  - In this paper, we interpret the new YY/T 0841-2011 standard and contrast the
      difference between it and GB9706.1-2007 standard. Then, we improved the current
      preventive maintenance work. After the improvement, we not only have more
      effective detection of the electrical safety performance of all kinds of medical
      electrical equipment, but also reduce the workload of clinical engineers, improve
      efficiency, and reduce the risk of electrical shock.

PMID- 25597089
TI  - [Discussion on the building of post market risk analysis method in hemodialysis
      device].
AB  - This paper discussed the building of post market risk analysis method in
      hemodialysis device from the point of government supervision. By proposing
      practical research methods for post market risk identification and estimation on
      hemodialysis device, providing technical guidance for government to put risk
      management of hemodialysis device into effect, and offering reference for
      enterprises to carry out post market risk evaluation on their products as well.

PMID- 25597090
TI  - [GC study of N,N-DMAC in medical polyurethane fiber membrane].
AB  - Medical polyurethane fiber membrane after extraction with water, and then
      establish the determination of N, N dimethyl acetamide (DMAC) in Medical
      polyurethane fiber membrane by GC, and discuss the analysis and evaluation of
      other extracts of polyurethane fiber membrane for the determination of DMAC in
      the linear range of the average recovery rate was more than 90%, the RSD 1.51%
      2.08% (n = 6). This method is simple, fast, sensitive and accurate, and may serve
      as a mass control method for DMAC in Medical polyurethane fiber membrane.

PMID- 25597091
TI  - [Quality control research of cold light source of endoscope].
AB  - This paper introduced the significance parameters of the quality control of cold
      light source of endoscope, expounded the importance and necessity of quality
      control of cold light source; it investigated several manufacturers, analyzed and
      discussed the main causes of the cold light source uneven, in order to realized
      the standard management and effective supervision on the cold light source, at
      the end, the next step quality control work was brought out, which provide
      technical support for quality supervision of cold light source.

PMID- 25597092
TI  - [Determination of residual cyclohexanone in disposable infusion set by gas
      chromatography].
AB  - An effective GC method was established for contents determination of the residual
      solvent of cyclohexanone in infusion sets for single use. The cyclohexanone in
      infusion sets for single use products were extracted with circular pump, using
      ethylalcohol as the extraction solven, then the extract followed by analysis of
      gas chromatography-tandem mass spectrometry. The method was simple, rapid,
      sensitive and accurate, Cyclohexanone showed good linearity in the range of (5.5
      190.9) MUg/mL, the correlation coefficient was 0.999 0, the detection limit (S/N
      = 3) was 0.133 MUg/mL and limits of quantitation (S/N = 10) was 1.33 MUg/mL. The
      spiked average recoveries ranged from 98% to 99%. The relative standard
      deviations (RSDs) of the method ranged from 1.03% to 1.98%. The method was
      simple, fast, sensitive and accurate, and may serve as a mass control method for
      residual cyclohexanone in disposable infusion sets for single use.

PMID- 25597093
TI  - [The current situation and consideration on the quality of medical device
      standards in China].
AB  - Through the analysis of the present problems of the quality of medical device
      standards in China, combined with the development trend of the last ten years of
      medical devices, the paper made proposals on the medical device standards quality
      evaluation system, so as to improve the medical device standards management level
      and the quality of medical device standard in our country.

PMID- 25597094
TI  - [The application of AI in medical consumable classifier].
AB  - Establish normal classifier of non-charge medical consumable and database of
      medical consumable inuse, is the basis of uniform classification and management
      of non-charge medical materials used in different hospital. It's an objective and
      effective method to classify by AI and set up the database, and has better
      classification accuracy.

PMID- 25597095
TI  - [Effects of PLGA absorbable membrane on preventing postoperative abdominal
      adhesion in rabbits].
AB  - OBJECTIVE: To investigate the effects of PLGA absorbable membrane in prevention
      of postoperative abdominal adhesion in rabbits. METHODS: 66 Japanese white
      rabbits were randomly divided into three groups: the normal control group n = 6,
      model control group n = 30 and PLGA group n = 30. Rabbits were received
      multifactor methods to establish postoperative abdominal adhesion models except
      for normal control group. The cecum wound was covered PLGA membrane in the PLGA
      group. At postoperative 1, 2, 4, 6 and 12 weeks, the abdominal cavities were
      reopened and the adhesive severity was graded blindly, and the hydroxyproline
      level in cecum tissue was measured and the cecum histopathology was observed.
      RESULTS: (1) the degree of adhesion and hydroxyproline level in model control
      group were significantly higher than those of normal control group (P < 0.05, P <
      0.01), while the degree of adhesion and hydroxyproline level in PLGA group were
      significantly lower than those of model control group (P < 0.05). (2) HE staining
      showed that cecum serosa had obviously inflammatory cell infiltration and
      fibroblast proliferation, while PLGA could inhibit fibroblast proliferation and
      reduce the inflammatory cell infiltration and collagen. CONCLUSION: PLGA
      absorbable membrane can inhibit fibroblast proliferation and collagen to prevent
      the experimental postoperative peritoneal adhesions.

PMID- 25597096
TI  - A hacker's guide to planet cooling.

PMID- 25597097
TI  - The end of economic growth? How the digital economy could lead to secular
      stagnation.

PMID- 25597098
TI  - Dancing with the asteroids. NASA's proposed human mission to a space rock has a
      bumpy road ahead.

PMID- 25597099
TI  - Bacteria? They love all manure.

PMID- 25597100
TI  - Theoretical particles, still theoretical. No signs of the rumored "sterile"
      neutrino.

PMID- 25597101
TI  - Parental controls. Pushy parents could harm kids' social skills.

PMID- 25597102
TI  - Health advice from a grizzly. What humans can learn from animals that sleep for
      months on end.

PMID- 25597103
TI  - From rain to ranges.

PMID- 25597104
TI  - The dust belt next door.

PMID- 25597105
TI  - When DNA means "do not ask".

PMID- 25597106
TI  - You: by the numbers. Can personal fitness monitors whip us--and health research-
      into shape?

PMID- 25597107
TI  - Better than Earth.

PMID- 25597108
TI  - A weakness in bacteria's fortress.

PMID- 25597109
TI  - A world of movement.

PMID- 25597110
TI  - Living large. Microscopes find beauty in the most unexpected places.

PMID- 25597112
TI  - In search of sunken treasure.

PMID- 25597111
TI  - Will we still enjoy Pinot noir?

PMID- 25597113
TI  - Why we have free will.

PMID- 25597114
TI  - Haemophilia.

PMID- 25597115
TI  - Born in the blood.

PMID- 25597116
TI  - Genie in a vector.

PMID- 25597117
TI  - Stretching time.

PMID- 25597118
TI  - The fix is in.

PMID- 25597119
TI  - Oral solutions.

PMID- 25597120
TI  - Balancing act.

PMID- 25597121
TI  - Joint effort.

PMID- 25597122
TI  - Dogged pursuit.

PMID- 25597124
TI  - Sass vs. substance. Twitter, mainstream media and academic blogs focus on
      surprisingly different scientific subjects.

PMID- 25597123
TI  - Here Be zombies.

PMID- 25597125
TI  - Self-care, survival and a sense of coherence.

PMID- 25597126
TI  - Burnt out and overwhelmed.

PMID- 25597127
TI  - Gains in maternal health being wiped out by Ebola.

PMID- 25597128
TI  - Project aims to halve preventable stillbirths by 2020.

PMID- 25597129
TI  - Second wave of industrial action for fair pay gets under way.

PMID- 25597130
TI  - 1. Avoiding back injury.
AB  - This article looks at healthcare professionals, in particular midwives, and
      considers how to maintain back health and prevent injury through principles of
      good practice. Knowledge of back pain, mindfulness in working conditions and
      modifications of current practice will reduce the risk of repetitive injury, and
      present management options in the short- and long term. Considerations on
      improving the 'working lifestyle' rather than quick fixes are ultimately the long
      term goal.

PMID- 25597131
TI  - Your feet were made for walking.
AB  - Our feet are made up of 52 bones: around a quarter of all the bones in the human
      body. At the bottom of each foot there are four layers of muscle designed to
      carry our weight and to help us run, jump, walk and skip. As a rule, we tend to
      ignore our feet; that is, until they hurt. A straw poll of midwives during the
      Primary Care 2014 conference in May revealed the majority to have foot pain. The
      aim of this short article is to outline the basics of foot function and to
      provide midwives with practical tips on foot care, which ought to help relieve
      some of that foot pain.

PMID- 25597132
TI  - Mindful midwifery: a phenomenological paradigm.
AB  - Mindfulness is a form of critical reflection that has been used by healthcare
      professionals for over a decade (Epstein 1999). Reflection and self-awareness are
      vital to being an ethical and trustworthy practitioner, to good communication and
      to establishing relationships (Johns 2000). Embedding reflection into the core of
      one's practice is a challenging task. It is easy to pay lip service to informed
      choice while in reality offering only a limited and predefined menu. Pressure to
      comply with guidelines can lead to subtle ways in which women are manipulated
      towards making a particular decision. Midwives are urged to provide woman-centred
      care, but often they are not taught or shown how to achieve this. This article
      explores how phenomenological research methodology provides a model for 'mindful
      midwifery' that seeks to improve the quality of midwives' relationships with the
      women in their care, through a process of 'bridling' and 'questioning'.

PMID- 25597133
TI  - Reflecting on resilience in midwifery.
AB  - In the first part of this paper we provide a brief explanation of resilience and
      outline what is known about resilience in healthcare professionals. We then
      summarise the findings from our recent study of resilience in UK midwifery, which
      used a closed online discussion forum to explore the experiences of midwives who
      described themselves as resilient. We note that the participants identified a
      number of workplace challenges, which they responded to with a range of day-to
      day and longer-term strategies. We reflect on what these findings might mean for
      midwifery practice, and where the gaps in knowledge remain.

PMID- 25597134
TI  - Do you have any children?
AB  - "Do you have any children?" It is a question often posed by the expectant mother
      as the midwife tends to their needs. For some, this enquiry may lead to an
      empathetic exchange and relationship building, while other midwives may shudder
      when they hear this question. Sadly, professional codes and boundaries do not
      always assist in the guidance of this exchange. Using Gibbs' reflective cycle
      (1998) as a framework, this article initially explores my motivations for the
      selection of responses I have used as a bereaved mother and midwife. Evaluation
      and analysis of these different approaches has given me an insight into how
      successfully they preserve the rapport I try to nurture with my clients but also
      how they might affect me. The reflective process has enabled me to understand how
      best to tackle the enquiry in future to safeguard my own feelings and that of the
      client, coming to the conclusion that honesty and truth-telling is probably the
      best practice.

PMID- 25597135
TI  - 3. Undiagnosed breech--part of midwifery practice.
AB  - This article discusses the background to undiagnosed breech and what a midwife
      can do to support a woman who is giving birth to a baby in an undiagnosed breech
      presentation. There is no evidence to support the use of emergency caesarean
      section when a breech is diagnosed in labour and it is a requirement of the
      Nursing and Midwifery Council rules and standards that registered midwives should
      have been taught, pre-registration, how to assist an undiagnosed breech
      presenting baby to be born.

PMID- 25597136
TI  - 3. Mentorship from the student perspective.

PMID- 25597137
TI  - Caring for ourselves.

PMID- 25597138
TI  - Unpacking emotional baggage.

PMID- 25597139
TI  - More hospitals make Top Performer status.

PMID- 25597140
TI  - What makes a Baldrige winner?

PMID- 25597141
TI  - Improving transitions within the hospital.

PMID- 25597142
TI  - Top 10 tech hazards include new worries.

PMID- 25597143
TI  - Cytokines and mother sporocysts in susceptible and resistant Bulinus truncatus
      snails infected with Schistosoma haematobium.
AB  - The presence of immunoreactive interleukin (IL-2), interferon gamma (IFN-gamma)
      and tumor necrosis factor alpha (TNF-alpha) in addition to the citation of mother
      sporscytes in cephalopodal musculature in the susceptible and resistance Bulinus
      truncatus the specific intermediate host for the trematode Schistosoma
      haematobium were investigated,. Using ELISA tests, Results indicated that the
      concentration of IL-2-like activity in the susceptible and resistant snails
      decreased significantly after infection then persisted at low levels until the
      4th week post exposure (WPE) in susceptible snails, while in resistant snails
      elevated during the second WPE, and returned to initial level at 3 and 4 WPE.
      Susceptible snails had low detectable levels of TNF-alpha and INF-gamma like
      activity after infection. However, the resistant snails had significant low
      levels of TNF-alpha and INF-gamma like-activity from 3 WPE until the 4th WPE
      without any sign of normalization. Histological sections in the head- foot region
      of susceptible and resistance B. truncatus infected with S. haematobium, mother
      sporocysts exists from 1 to 7(day post exposure) DPE, in the susceptible snail
      the mother sporocysts were found as single, multiple and mature types. No mother
      sporocysts were appear in the lip and mantle of the snail on 2, 5, 7 DPE and on 1
      3, 6 DPE respectively. In the resistant snails few mother sporocysts were found
      in the lip, mantle and tentacles. The results showed that schistosome-resistant
      Bulinus can be an alternative strategy for the control of schistosomiasis.

PMID- 25597144
TI  - Pharmacological and antioxidant actions of garlic and.or onion in non-alcoholic
      fatty liver disease (NAFLD) in rats.
AB  - Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat
      induced liver injury, ranging from mild steatosis to cirrhosis and liver failure.
      This study investigates the hepatoprotective properties of garlic and onion in
      NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9
      groups; normal (I), NAFLD induced with high fat diet (HFD; II), NAFLD switched to
      regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with garlic (IV, V), onion
      (VI, VII) or the combined garlic+onion (VIII, IX) respectively. A NAFLD rat model
      was established by feeding the animals with a high-fat diet for 12 wk. These
      animals were then treated with garlic or/and onion or vehicle for 8 wk (weeks 13
      20) and then killed to obtain serum samples and liver tissues. Liver histology,
      lipids, parameters of oxidative stress, TNF-alpha and TGF-beta were measured. The
      liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate
      lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin,
      cholesterol, triglycerides, TNF-alpha, TGF-beta and hepatic MDA' were
      significantly increased (P < 0.05) compared with normal group. This was
      accompanied with reduction of hepatic GSH, GR, GPx, GST, SOD and serum
      adiponectin. These changes were to a less degree in NAFLD-RD group. Combined
      administration of garlic+onion produced a better and significant decrease in
      liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation
      versus each one alone. In the same time, NAFLD-induced inflammation was also
      mitigated via reduction of TNF-alpha and TGF-beta. In addition, these results
      were better in the group IX versus group VIII.

PMID- 25597145
TI  - Anatomical and surface morphology of Hedruris lutjanenses sp. n. (Nematoda:
      Hedruridae) from the common marinewater fish Lutjanus synagris in Damietta,
      Egypt.
AB  - The description and tegumental ultrastructure of nematode Hedruris lutjanenses
      sp. n. collected from marine Lane Snapper fish Lutjanus synagris Linnaeus, 1758
      collected at Manzala Lake, Damietta, Egypt was studied by light and Scanning
      Electron Microscopy (SEM). The new species is mainly characterized by that the
      buccal capsule is surrounded by four pseudolapia; one small and three larger
      pseudolapia, each one bears a number of papillae arranged irregularly on its
      surface and the presence of one pair of precloacal papillae and nine pairs of
      postcloacal ones in males.

PMID- 25597146
TI  - Molecular cloning and expression of the Leishmania tropica KMP-11 gene.
AB  - Kinetoplastid membrane protein-11 (KMP-11) is a small protein of 11 kDa present
      in all kinetoplastid protozoa studded so far. This protein which is highly
      expressed in all stages of the Leishmania life cycle is considered a potential
      candidate for a leishmaniasis vaccine against many leishmania species. KMP-11 has
      been recently described in Leishmania tropica. In the present study, the KMP-11
      gene was extracted from L. tropica by PCR using two oligonucleotide primers
      designed to amplify the entire coding region of this gene. Then, the purified PCR
      products were successfully ligated into a high expression vector the pRSET-GFP.
      This expression vector provides the opportunity to clone the desired insert as a
      fusion protein with a GFP and a tag, polyhistidine region. The GFP use as a
      carrier to improve immune response and the polyhistidine tag facilitates
      detection of the expressed protein with anti-His antibodies and also purification
      of the protein using affinity purification. After wards KMP-11 coding region was
      sequenced and the recombinant protein was induced and purified from Escherichia
      coli cultures. The results of the present study will increase our knowledge about
      molecular cloning and expression of the L. tropica KMP-11 gene, and this may be
      used as an effective target for controlling cutenous leishmaniasis.

PMID- 25597147
TI  - Screening of Toxoplasma gondii infection among childbearing age females and
      assessment of nurses' role in prevention and control of toxoplasmosis.
AB  - Toxoplasmosis, caused by Toxoplasma gondii is an obligate intracellular zoonotic
      protozoan parasite, with a worldwide distribution particularly in Arab countries
      including Egypt. The study evaluated toxoplasmosis infection among childbearing
      age Egyptian females and assessed the military nursing staff knowledge, attitude
      and compliance to toxoplasmosis prevention and control measures. The study was
      conductedin a general military hospital. RESEARCH DESIGN: CROSS-section
      descriptive research design was used to conduct this study. The subjects
      consisted of 14 young females (11 were in-patients undergoing gynecological
      treatment in a military hospital and 3 were staff nurses. On the other hand, 44
      staff nurses were available for assessment who met the inclusion criteria. TOOLS:
      4 tools were used for data collection: first consisted of self-administered
      questionnaires to assess nurses' socio-demographic data and knowledge, second
      rating scale to assess nurses' attitude towards toxoplasmosis infection and its
      prevention, third performance check list to measure nurses' compliance to
      infection control measures, and fourth measured the anti-Toxoplasma antibodies by
      commercial indirect hemagglutination test (IHAT). The results showed that almost
      half of the nurses had satisfactory levels of knowledge, attitude, and compliance
      to toxoplasmosis infection control measures. 22.2% of the pregnant women and 20%
      of non-pregnant ones showed antibodies against T. gondii. Thus health education
      about toxoplasmosis should be tailored to women whether married or single to help
      in avoiding the risk of infection. Frequent periodic IHAT should be done for
      people who continuously contact with cats. Adherence to strict infection
      prevention measures is a must to eliminate exposure to toxoplasmosis infection.
      Training intervention should be implemented to achieve successful improvement in
      knowledge, attitude, and compliance of toxoplasmosis control measures.

PMID- 25597148
TI  - Initial experience of surgical microwave tissue precoagulation in liver resection
      for hepatocellular carcinoma in cirrhotic liver.
AB  - Surgical hepatic resection has been considered as the first-line treatment which
      is most effective and radical treatment for HCC, however, HCC is usually
      associated with poor liver function owing to chronic hepatitis or liver
      cirrhosis. Techniques that can eradicate the tumor and also preserve liver
      function are needed. Moreover, hepatic resection, in the presence of cirrhosis,
      raises special problem of high risk as hemorrhage and liver failure, thus, good
      clinical results can only be achieved by minimizing operative blood loss, time of
      the intervention as well as the hepatic reserve. The tremendous progress in
      microwave technology has recently attracted considerable attention. This study
      evaluated the feasibility of this new liver transection technique demonstrating
      the high performance of this procedure, the accuracy in terms of squeeze effect
      on veins and portal branch and in terms of reducing the intra operative blood
      loss, and minimizing the operative time for safe hepatectomy. Twenty-six
      consecutive patients a first-time diagnosis of hepatocellular carcinoma (HCC) on
      top of liver cirrhosis were recruited for the study, from August 2011 to January
      2013. All patients were subjected to full clinical examination, laboratory
      investigations, abdomen ultrasound (U/S), triphasic computed tomographic liver
      scan (CT) and dynamic magnetic resonance imaging (MRI) in some doubtful cases.
      Inclusion requirements were presence of resectable disease without vascular
      invasion or extrahepatic spread at imaging, Child-Pugh class A & B (Score 7)
      liver cirrhosis, (INR) < 1.6 or platelet count) 60 000/mm3 with no previous
      treatment. Patients were treated by applying pre-coagulation of the liver
      transection lines using microwave probe positioned in parallel to the line of
      resection by open approach after intra-operative U/S assessment for localization
      of the tumor and line of resection. The procedures were performed under general
      anesthesia. Mobilization of the liver was not necessary to be done in all cases.
      Intra-operative ultrasound (Aloka, Tokyo, Japan) was used to exclude lesions not
      detected pre-operatively (operative surprise), to define the location, number and
      size of the tumor and to identify large intra-hepatic large vascular and biliary
      structures, and guide insertion of the microwave applicator. Intraoperative
      ultrasound was used again, to assess that the line of resection was done. Primary
      endpoints documented were total operative time, time for liver parenchyma
      transection, intraoperative blood loss and blood transfusion requirements.
      Secondary endpoints included postoperative complications, mortality and intensive
      care unit (ICU) together with hospital stay.

PMID- 25597149
TI  - A description of Haemogregarina species naturally infecting white-spotted gecko
      (Tarentola annularis) in Qena, Egypt.
AB  - The present study describes the developmental stages of Haemogregarina species in
      the blood and tissues of naturally infecting white-spotted gecko Tarentola
      annularis collected from Qena, Egypt. Different parasite's forms were observed
      infecting the erythrocytes. The gamonts enclosed within parasitophorous vacuole
      and seems to have no clear effect on the host cell especially in case of immature
      parasite forms. But in the presence of mature gamonts the host cell nucleus
      displaced. The parasitaemia level is up to 280 per 10,000 erythrocytes counted.
      Trophozoites and gamonts have been recognized in the blood smears. The rounded
      trophozoite diameter is 3.84 +/-0.87 MUm, while the elongated trophozoite
      measured 4.42 +/- 0.69 x 2.8 +/- 0.56 MUm. The mature gamonts were differentiated
      into two forms; short gamont measuring 10.82 +/- 0.82 x 3.30 +/- 0.73 MUm (range:
      10-12.1 x 2.2-4.4 MUm) and the long gamont measured 14.67 +/- 0.83 x 3.96 +/-
      0.77 MUm (range: 14.1-16.5 x 3.3-5.5 MUm). Merogony carried out only in the
      endothelial cells of the blood capillaries in the lung. Different merogonic
      stages have been recognized and differentiated in two forms; micromeront measured
      13.25 +/- 0.50 x 12 +/- 0.0 MUm and produces a few number of large merozoites,
      macromeront measured 19.75+0.87x13.25+0.50 im and produces more small sized
      merozoites. The gamonts and merozoites have the general characteristic
      ultrastructures of the Apicomplexa containing components of the apical complex,
      e.g. pellicle, micronemes, rhoptries, and few dense bodies and subpellicular
      microtubules.

PMID- 25597150
TI  - Hydrocarbon insecticides: their risks for environment and human health.
AB  - Insecticides are used to control diseases spread by arthropods, but theys vary
      greatly in toxicity. Toxicity depends on the chemical and physical properties of
      a substance, and may be defined as the quality of being poisonous or harmful to
      animals or plants. Poisons have many different modes of action, but in general
      cause biochemical changes which interfere with normal body functions. Toxicity
      can be either acute or chronic. Acute toxicity is the ability of a substance to
      cause harmful effects which develop rapidly following absorption, i.e. a few
      hours or a day. Chronic toxicity is the ability of a substance to cause adverse
      health effects resulting from long-term exposure to a substance. There is a great
      range in the toxicity of insecticides to humans. The relative hazard of an
      insecticide is dependent upon the toxicity of the pesticide, the dose received
      and the length of time exposed. A hazard can be defined as a source of danger.
      The great majority of insecticides are poisonous to man and his beneficial
      insects and animals and are carcinogenic agents particularly, the halogenated
      hydrocarbons containing benzene ring.

PMID- 25597151
TI  - Description of two new cercariae (an echinostome cercaria and a xiphidiocercaria)
      procured from Biomphalaria pfeifferi (Krauss) from Nigeria.
AB  - During parasitological examination of Biomphalaria pfeifferi snails obtained from
      Niger state (Nigeria), 2 new types of cercariae were found. They are identified
      to the level of referring to the major group and described here for the first
      time. They were examined viable and stained with vital stains as well as fixed in
      70% alcohol. They were drawn with a camera lucida and photographed. They are
      identified as an echinostome cercaria and a xiphidiocercaria. The echinostome is
      characterized by having a ventral sucker almost double in size the oral one. It
      has a semicircular structure located beyond the oral sucker. Three pairs of
      penetration glands are found at the anterior portion of the body. The number of
      collar spines is relatively large (44-46). The flame cellsare 17 x 2 in number.
      Two main lateral excretory ducts extend anteriorly, form two typical echinostome
      loops then pass posteriorly to open together in a diverticulated excretory
      vesicle. Its tail is relatively long and flattened with 3 fin folds. The tail
      (640 MUm) is longer than the body (475 MUm). The xiphidiocercaria belongs to the
      "ornatae" group. It is relatively small (180.5 x 110 MUm) with a long stylet (30
      MUm). Its oral sucker is one and half times the size of the ventral sucker. Two
      excretory ducts extend posteriorly in both sides and become dilated and unite to
      open in a circular excretoryvesicle. Tail is slender shorter than the body and
      has a dorso-ventral fin fold.

PMID- 25597153
TI  - Preliminary study on cryptosporidiosis in livestock from Kuwait.
AB  - Out of 225 fecal samples (40 of calves, 128 of lambs and 57 of goat kids)
      received in the Veterinary Laboratories, Kuwait, 43 (19.1%) were found to be
      positive for Cryptosporidium using the conventional method, modified acid-fast
      stain, and the immunologic technique, the immuno-chromatography assay. Calf fecal
      samples showed the highest infection rate (37.5%), followed by goat kids (21%)
      and then Lambs (12.5%). Results obtained by conventional method were found to be
      consistent with those detected using the immunologic technique.

PMID- 25597152
TI  - Bronchial aspirates glucose level as indicator for methicillin-resistant
      Staphylococcus aureus (MRSA) in intubated mechanically ventilated patients.
AB  - This study evaluated if the level of glucose in bronchial aspirate serves as
      indicator for the risk of MRSA infection in intubated mechanically ventilated ICU
      patients. A total of 50 critically ill patients was enrolled and were under tight
      glycemic control to abolish the effect of hyperglycemia on bronchial secretion,
      if they were expected to require mechanical ventilation for more than 48 hours.
      Bronchial aspirates were detected for glucose and sent twice weekly for
      microbiological analysis and whenever an MRSA was expected. The results showed
      that all the patients had glucose tested in bronchial aspirates. Glucose was
      detected in bronchial aspirates of 28 of the 50 patients. Glucose in bronchial
      aspirates in these patients ranged between (2.9-5.1 mmol/l). MRSA was detected in
      22 patients where 28 were MRSA free of the MRSA patients 19 had positive glucose
      where glucose was positive in 28 patients of them 19 (86.4%) where MRSA positive
      to 9 with no MRSA (32.1%).The risk of having MRSA present markedly increased
      significantly in the presence of glucose: (p value .001).

PMID- 25597154
TI  - Prevalence of anti-Toxoplasma gondii antibodies in aborted ewes in Kuwait.
AB  - Serum samples from 528 aborted ewes from different sheep flocks in Kuwait were
      tested for Toxoplasma gondii. The indirect hemagglutination test (IHAT) was used
      with a titer of 1:80 considered positive. Antibodies to T. gondii were found in
      94 (17.8%). The highest number of positive ewes (23; 24.5%) had a titer of 1:640.
      Only one aborted ewe had a titer of 1:2560. This study is the first to report
      Toxoplasma infection in sheep which may pose risk to humans who consume under
      cooked mutton. The detection of Toxoplasma antibodies in aborted ewes refers to
      the implication of toxoplasmosis in abortion among sheep in Kuwait.

PMID- 25597155
TI  - Prevalence of schistosomiasis in Al-Baha Province, Saudi Arabia in years 2012 and
      2013 (prospective and comparative study).
AB  - The rate of human schistosomiasis increased in Al- Baha Province, Saudi Arabia in
      the last few years. So, it was necessary to study the prevalence of human
      schistosomiasis in Al-Baha Province over the period of the two years (2012-2013).
      In general, there was a decline in the prevalence of schistosomiasis in Al-Baha
      over the study period and it was significantly less in 2013 than it was in 2012.
      Schistosomiasis infection rate was affected by host sex as males had higher
      infection rate than females. Age group of 15-44 showed the highest infection
      rate. Prevalence of schistosomiasis in Saudi people was significantly higher than
      it was in non-Saudi or immigrant ones. Thus, more attention should be paid to Al
      Baha area in the future schistosome control programmes.

PMID- 25597156
TI  - An interventional program for nursing staff on selected mass gathering infectious
      diseases at Hajj.
AB  - This work improved military nursing staff knowledge on selected mass gathering
      infectious diseases at Hajj. The results showed that only (20%) of the
      participating nurses attended training program about health hazard during
      pilgrim. But only (40.0%) of them found the training programs were specific to
      nurses. Majority found the program useful (70.0%), and the average duration of
      this training program in weeks was 3.5+1.1. There was significant improvement P =
      < 0.001, of correct knowledge about meningitis regarding causes, organisms, mode
      of spread, people at risk, transmission, prevention and treatment, the highest
      improvement was in causes of meningitis the lowest was in adult vaccination. 25%
      of participants had adequate knowledge (> 60% from total score) in pre-test 93%
      in post-test 72% after 3 month with significant difference among tests regarding
      adequate knowledge. There was significant improvement of correct knowledge P =
      <0.001 about seasonal influenza and respiratory diseases during pilgrim, the
      highest improvement was in influenza vaccine strains the lowest was in antiviral
      drugs. 23% of nurses had adequate knowledge (> 60% from total score) in pre-test
      94% in post-test 66% after 3 month with significant difference among tests
      regarding adequate knowledge. There was significant improvement P = < 0.001 of
      correct knowledge about gastrointestinal diseases and food poisoning during
      pilgrim among nurses at military hospital, the highest improvement was in risk
      factors of food poisoning the lowest was in what GE patient should do. 22% of
      participants had adequate knowledge (> 60% from total score) in pre-test 91% in
      post-test 58% after 3 month with significant difference among tests regarding
      adequate knowledge. There was significant improvement P = < 0.001 of correct
      knowledge about heat exhaustion during pilgrim among nurses at military hospital,
      the highest improvement was in non-communicable diseases the lowest was in sun
      stroke prevention. 27% of participant had adequate knowledge (> 60% from total
      score) in the pre-test 94% in the post-test 74% after 3 month with significant
      difference among pre, post and FU regarding adequate knowledge. Also, there were
      significant improvement P = < 0.001 of correct knowledge about hypertension,
      dengue fever, skin scalding & others diseases during pilgrim among nurses at
      military hospital, the highest improvement was in skin scalding prevention the
      lowest was in first aid bag. 28% of participant had adequate knowledge (> 60%
      from total score) in the pre-test 92% in the post-test 61% after 3 month with
      significant difference among pre, post and FU regarding adequate knowledge. There
      was a significant difference between total knowledge score according to
      education, and work experience (P > 0.05). in the pre, post and after 3 month in
      age and in all intervention time in department the highest was ICU then ward then
      operation room.

PMID- 25597157
TI  - Natural and experimental evidence of viscerotropic infection caused by Leishmania
      tropica from North Sinai, Egypt.
AB  - Cutaneous leishmaniasis (CL) is a neglected clinical form that is quite prevalent
      in Eastern North parts of the country in Sinai Peninsula. Leishmania tropica was
      identified by previous reports as the causative agent responsible for
      viscerotropic infections in-patients and experimental animals. Here, we reported
      the viscerotropic infections from naturally infected rodent Gerbillus pyramidum
      floweri collected from North-Sinai. Footpad and tail lesions, spleenomegaly, and
      malformed dark-colored spleen were the characteristic CL symptoms. The spleen of
      the rodent found positive to amastigote impression smear. ITS-1 DNA was sequenced
      and revealed 100% identity of the strain in the current study to the other L.
      tropica sequences identified from the patients with the suspected CL and
      inhabited the same study area. The current findings confirmed the susceptibility
      of gerbil to L. tropica, and raise the concerns for the role of rodents as
      accidental host suffering the infections. The susceptibility of wild and
      experimental rodents to the same L. tropica strain was also investigated; BALB/c
      and G. pyramidum were more susceptible to L. tropica (24.33 +/- 4.37 and 25 +/-
      4.58 days post-infection, respectively). Similar viscerotropic pathologies were
      reported in experimental infection of only golden hamster (~ 120 days post
      infection), and G. p. floweri (~ 160 days post-infection).

PMID- 25597158
TI  - Pfeifferinella sp. (Pfeifferinellidae, Apicomplexa) infecting the fresh water
      snail Pirenella conica light and electron microscope studies.
AB  - Coccidian oocysts were proved to be found in 70 of 100 collected Pirenella conica
      snails, with a natural infection of 70%. It was observed that, Pfeifferinella sp.
      was transferred between hepatopancreas and small intestine of snail. The
      prepatent period of Pfeifferinella sp. infecting P. conica snails ranged from 14
      18 days and the patent period was reached 50 days (P.I.). Merogony stages were
      the early stages observed in this study. These stages were observed in the
      hepatopancreas and in a large clear parasiteophorous vacuole (PV). In snails
      killed 4 days P.I. immature meronts were measured 12 x 10 MUm containing 8
      nuclei. Meanwhile, mature meronts with about 6 differentiated merozoites were
      detected as early as 6 days P.I., and measured 3.1 x 1.4 MUm. The earliest
      gametogonic stages were seen in the intestine of Pirenella conica snails killed
      12 days P.I. Microgamonts contained about 4 nuclei and measured 7.9 x6.7 MUm. The
      macrogamonts measured 7.3 x 5.6 MUm. Macrogametes were characterized by the
      presence of the vaginal tube, this tube measured 4.3 x 1.1 MUm. Fertilization was
      occurred in the intestine of the infected snails at 12 days P.I. Zygotes
      developed into young oocysts after fertilization. Sporogony occurred in the
      intestine. In the earliest stage, the nucleus of young oocyst was occupied the
      central position that were observed through the examination of the intestine of
      infected Pirenella snails at 14 day P.I. These oocysts were found to be colorless
      and ellipsoid or spherical in shape measured 9.5 x 8.5 MUm. The oocyst wall
      consists of two layers, micropyle and micropyle cap were not observed in these
      oocysts, and wall forming bodies were arranged at the periphery of oocyst
      directly under the developed oocyst wall. Sporulated oocyst contains 8
      sporozoites filling the entire cavity of the oocyst without sporocyst formation.
      Fully sporulated oocysts were excreted in the faces of infected snails from 14-18
      day P.I., these oocysts measured 9.5 x 8.5 MUm, Micropyle was absent and while a
      residual body was observed.

PMID- 25597159
TI  - The effect of larval and adult nutrition on survival and fecundity of dengue
      vector Aedes albopictus Skuse (Diptera: Culicidae).
AB  - The effect of larval and adult nutrition on survival and fecundity of the dengue
      vector Aedes albopictus Skuse (Diptera: Culicidae) were studied under laboratory
      conditions, the energy for the physiological activities for both male and female
      mosquitoes is provided largely by their reserves during larval stage and affected
      by adult diets. Two groups of larvae (A, B) were reared at 27 +/- 3 degrees C, 70
      80% R.H. and DL. 12: 12. Group (A) with 200 larvae (high larval diet) and Group
      (B) with 600 larvae (low larval diet). Ae. albopictus exhibited increased
      fecundity and egg hatch success. Immature development was quick. Immature
      survival was high, with lowest rate in the pupal stage. Highest longevity was
      observed in large females fed water + 10% sucrose solution (29.571 +/- 0.415
      days) while the lowest one was (1.3 +/- 0.132 days) in starved small females.
      Large females have significantly (P < 0.001) higher fecundity than smaller
      females, regardless of whether the females were provided 10% sucrose solution or
      not (524 +/- 0.203 eggs/group 159.714 +/- 0.1997 eggs/group), respectively. The
      addition of 10% sucrose solution significantly (P < 0.001) increase the fecundity
      regardless of whether large or small females (657.9 +/- 0.2198 eggs/group,
      242.429 +/- 0.119 eggs/group), respectively.

PMID- 25597160
TI  - Diagnosis and treatment of cryptosporidiosis: an update review.
AB  - Cryptosporidiosis represents a major public health problem which transmitted by
      contamination of food or water by sporulated Cryptosporidial oocyst. Causing self
      limited diarrhea in immunocompetent person and chronic and life threatening
      diarrhea among immunocompromised individuals. It can be diagnosed by
      concentration and detection of its Oocyst in different environmental samples and
      water by microscopic and immunological examination such as enzyme immunoassay
      (ELISA) for parasite antigens and nucleic acid amplification assay as well as use
      of molecular techniques such as Polymerase Chain Reaction (PCR). Treatment is
      face challenges, Macrolides, Paramomycin, Nitazoxanide and Mirazid. All these
      drugs have partial efficacy in reducing disease severity in immunocompetent
      individuals. Nitazoxanide has partial efficacy in immunocompromised individuals.
      Resolution of Cryptosporidiosis can be maintained with effective Highly Active
      Antiretroviral Therapy (HAART).

PMID- 25597161
TI  - Urothelial carcinoma of the urinary bladder mixed with squamous differentiation
      or squamous cell carcinoma in areas with schistosomiasis is showing high risk of
      recurrence and poor survival.
AB  - In schistosomiasis haematobium areas endemic, bladder cancer is the first cause
      of malignancy in men and fourth in women. The chronic schistosomiasis would lead
      to variant histologic patterns which manifest in squamous cell carcinoma (SCC) or
      squamous differentiation (SqD). This study evaluated the clinical outcome after
      radical cystectomy (RC) in patients with urothelial carcinoma (UC) mixed with SCC
      or SqD, Comparison was done with two arms of pure UC and pure SCC, indication for
      RC was muscle-invasive-disease, and evaluation included recurrence, metastases,
      and overall survival. The data of patients treated with RC for muscle-invasive
      disease, selection was revised for 127 patients with urothelial carcinoma mixed
      with SCC/SqD, two comparative arms were 100 patients with pure UC, and 100
      patients had pure SCC. Follow up was on 8 months, 3 years, and 5 years to detect
      recurrence, metastasis, and overall survival in the three groups. The results
      showed that by comparison of disease aggressiveness in the three groups regarding
      recurrence, metastasis, and overall survival was analysed. Overall survival with
      mixed tumours was significantly lower than pure UC or SCC, recurrence and
      metastases were higher in mixed tumour which was an independent factor for poor
      prognosis and low survival.

PMID- 25597162
TI  - Efficacy of pentoxifylline as an antifibrotic drug in experimental murine
      schistosomal hepatic fibrosis.
AB  - This study evaluated the possible antifibrotic effect of pentoxifylline on
      experimentally induced schistosomal hepatic fibrosis and its effect on serum
      leptin and transforming growth factor-beta1 levels as possible antifibrotic
      mechanisms in correlation with the hepatic fibrosis indices. A total of ninety
      clean laboratories bred, males Swiss, albino mice were included, of which ten
      mice served as a control non-infected, non-treated group and sacrificed at one
      time. Eighty mice, each was subcutaneously infected with 50 Schistosoma mansoni
      cercariae and classified into groups: GI (infected & non-treated), GII (infected
      & treated with Mirazid), GIII (infected & treated with Pentoxifylline) and GIV
      (infected & treated with a combination of Mirazid and Pentoxifylline). Each group
      was further subdivided into 2 subgroups; subgroup 'a' which started treatment at
      6th week post-infection (P.I.) and sacrificed at the end of 9th week P.I and
      subgroup 'b' which started treatment at 14th week P.I and sacrificed at the end
      of 17th week P.I. The efficacy of the treatment was assessed by histopathological
      examination of the liver with measurement of granuloma sizes, estimation of
      hydroxyproline content in the liver, and assessment of serum levels of leptin and
      transforming growth factor- beta1 (TGF-beta1).Mirazid (MZD) caused significant
      reductions in granuloma sizes and hepatic hydroxyproline content and caused non
      significant reductions in serum levels of leptinand transforming growth factor-
      beta1 t 9th & 17t hweeks P.II(GIII. Pentoxifylline (PTX) caused significant
      reductions in granuloma sizes, hepatic hydroxyproline, and serum levels of leptin
      and transforming growth factor- beta1 t the 9"th& 17kt weeks P.II (GIII. While
      combined therapy of both MZD & PTX in GIIVcaused more reductions in granuloma
      sizes, hepatic hydroxyproline, and serum levels of leptin and TGF- beta1 t the
      9th & 17th weeks P.IIwhen compared to the other groups.

PMID- 25597163
TI  - Prevalence of schistosomiasis among patients attending Qena General Hospital over
      the years 2011 and 2012.
AB  - Schistosomiasis is a public health problem in Egypt. To detect the prevalence of
      schistosomiasis in Qena Governorate, 1601 urine and stool samples of patients
      attending Qena General Hospital were examined of whom 1601 patients had urinary
      symptoms and 893 patients had dysentery and bloody stool. Sheets were filled out
      on each patient. Also, a total of 7590 Bulinus truncatus and Biomphalaria
      alexandrina snails were collected from water bodies in Qena Governorate. The
      overall prevalence of S. haematobium was 13.9%; with maximum among 6-18 year-old
      age group and higher in males than in females. Risk factors for S. haematobium
      infection were this age group; particularly males. However, males swim and play
      in water bodies and women wash cloths and utensils there, and children swimming
      or playing in canals. The S. haematobium peak of infection was in winter
      correlated with the highest prevalence in Dandara City, Qena City, Awlad-Amr and
      El Hijarat. S. mansoni were negative in the examined individuals. The infective
      rate among snails was 1.82% in B. truncatus and 0.0% among B. alexandrina and M.
      tuberculata.

PMID- 25597164
TI  - Patient safety attitude among health care providers in family health care centers
      in Cairo governorate.
AB  - Two hundred and eighty Health care; physicians, nurses and technicians were
      included in the study, 133 (47.5) from 6th discrete HCF, 54 (19.3%) from Duwaiqa
      and 93 (33.2%) from Al Haggana. Ages ranged between 22 and 59 years (35.14 +/-
      10.13), years of experience in the study group ranged between 1 and 35 years
      (8.72 +/- 8.18) and years of work in group ranged between 1 & 40 years (10.43 +/-
      8.33). Doctors and nurses were males (72.55%) & females (86%) respectively while
      technicians were mostly males (60%). The teamwork climate score was 3.98 +/-
      0.87, 64.0% answered high or very high, 16.4% answered inadequate and 18% had
      answered few or very few. Safety climate score was 3.61 +/- 0.63, 49.28% had high
      or very high score, 17.14% answered inadequate and 32.15% had answered few or
      very few. Job satisfaction score was 3.91 +/- 0.80, 32.15% had answered few or
      very few, 17.14% answered inadequate and 49.28% answered high or very high.
      Stress recognition score was 3.61 +/- 0.79, 25% had answered few or very few,
      28.6% answered inadequate and 45.7% answered high or very high. Perception of
      management score was 3.48 +/- 0.80, 23.2% had answered few or very few, 17.8%
      answered inadequate and 57.6% answered high or very high. Working condition score
      was 3.51 +/- 0.84, 46.8% had answered few or very few, 17.1% answered inadequate
      and 35.7% answered high or very high. A significant difference regarding team
      work score, safety climate score, perception of management score, working
      condition score with highest value in doctors and lowest in technicians. On the
      other hand no significant difference was detected regarding job satisfaction
      score and stress recognition score. A significant difference regarding team work
      score, safety climate score and perception of management score with high values
      among older groups. No significant difference was detected regarding job
      satisfaction score, stress recognition score and working condition score. Also, a
      significant difference regarding team work score and safety climate score with
      higher value in males. Significant difference regarding job satisfaction score
      and working condition score was detected with higher value in females. No
      significant difference was detected regarding stress recognition score and
      perception of management scores.

PMID- 25597165
TI  - Comparison between ELISA and various stains techniques in laboratory diagnosis of
      cryptosporidiosis.
AB  - Cryptosporidium spp. is an important parasitic protozoa causing diarrhea which is
      a severe life-threatening diarrhea especially in immunocompromised hosts. We
      aimed to evaluate the usefulness of detection of Cryptosporidium spp. copro
      antigen from fecal specimens by using enzyme linked immunosorbent assay (ELISA)
      test and comparing its sensitivity and specificity with some staining methods.
      The results revealed that Modified Acid-Fast stain is considered better than
      Giemsa in detecting Cryptosporidium species oocysts in faecal smears as their
      sensitivity were 67.5% and 53.75% respectively. On contrary, ELISA technique is
      considered the best method used for detection of cryptosporidial infection as its
      sensitivity is 90%.

PMID- 25597166
TI  - Prevalence of intestinal parasites and its impact on nutritional status among
      preschool children living in Damanhur City, El-Behera Governorate, Egypt.
AB  - This cross sectional study was done in Damanhur City, the Capital of El-Behera
      Governorate to detect the prevalence of intestinal parasitic infection among
      preschool aged children and to find out its effect on their nutritional status.
      Five-hundreds children aged between 2-6 years were enrolled; a detailed
      questionnaire, complete clinical and anthropometric assessment as well as
      complete stool analysis and blood picture were done. The study revealed that
      51.8% preschool children were infected; Cysts of Entamoeba histolytica and
      Giardia lamblia were found in 16.8%, and 14.8% respectively. In 1.8% of cases,
      both cysts were found together. Ova of Ascaris lumbricoides, Enterobius
      vermicularis, Ancylostoma duodenale and Hymenolepis nana were detected in 14%,
      3.4%, 5% & 0.2% of cases, respectively. In 0.4% of cases, ova of A. lumbricoides
      and E. vermicularis were found together. Mixed infections were found in 3.6% of
      children. Significantly lower weight for age z-score (WAZ) and weight for height
      z-score (WHZ) were found among infested children compared to non-infested ones (P
      < 0.05). Moreover, stunting was found in 44.1%, underweight in 39.1% and wasting
      in 11.5% of infested children. Prevalence of anemia among all studied population
      was 39%; 48.6% in infested group compared to 28.8% in non-infested children (x =
      20, P < 0.001). Improper hand washing, and playing in the street bare footed,
      together with playing with animals and family history of parasitic infestation
      were considered the independent predictors of parasitic infestation by using
      binary logistic regression.

PMID- 25597167
TI  - Predictive value of phosphorylated insulin-like growth factor binding protein-1
      (PIGFBP-1) (bedside test) in preterm labor.
AB  - This study evaluated the predictive value of phosphorylated insulin like growth
      factor binding protein-1 in cervical secretion as bedside test for prediction of
      preterm labor in symptomatic women. A total of 57 patients with singleton
      pregnancy at 24-34 weeks gestation, with symptoms suggestive of preterm labor
      were included in this study. A rapid cervical sample for PIGFBP-1 determination
      (Actim partus test, Medix Biochemical, and Kaunianen, Finland) was taken by means
      of a polyester-tipped swab during a speculum examination of the cervix, and
      extracted with specimen- extraction solution. We analyzed the prevalence of
      preterm labor in these patients within seven days upon admission. And calculate
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) for PIGFBP-1. This study was done at Kuwait Oil Company hospital
      (KOC) and Taiba hospital (Kuwait) during the period between April 2011 and June
      2012. The test was positive in 50.9% of patients and negative in 49.1%, among
      those tests was positive 64% delivered less than a week, and among those tests
      was negative 35.7 delivered less than one week, with 74.3% sensitivity, 61%
      spesivity, 76.3% PPV and 73.6% NPV.

PMID- 25597168
TI  - [Variation trend of male fertility and semen parameters].
AB  - In recent years, the variation trend of male fertility and semen parameters has
      aroused much academic controversy and become a focus of public attention. For the
      assessment of male fertility, female pregnancy is regarded as a gold standard,
      but semen parameters are commonly used as surrogate or indirect evidence in
      clinical practice and laboratory research. The reference range of se- men
      parameters being used in China is based on the WHO recommended data and lacks the
      specific reference value for healthy Chinese men. No definite conclusion has yet
      been derived from studies at home and abroad on the general variation trend of
      semen parameters worldwide, but many researchers agree on the decline of semen
      quality in some areas of the world. Long-term continuous prospective studies are
      needed for the evaluation and prediction of the general variation trend of semen
      quality.

PMID- 25597169
TI  - [Construction, expression, and identification of the gene of human anti-prostate
      specific membrane antigen single-chain antibody].
AB  - OBJECTIVE: To construct, express and purify human fusion proteins composed of a
      single-chain antibody fragment scFv that recognizes the prostate specific
      membrane antigen (PSMA) protein, Fdt, HA2 and tp, and to analyze the binding
      activity of the expressed fusion proteins. METHODS: The fusion protein genes
      scFv, scFv-tp, and scFv-Fdt-HA2-tp were amplified by PCR, and the genes obtained
      were then cloned into the expression vector pET28 and expressed in E. coli BL21.
      The expressed products were identified by SDS-PAGE and Western blot and purified
      with Ni(2+)-NTA chelating agarose. The antigen-binding activity of the fusion
      proteins was determined by ELISA. RESULTS: The human anti-PSMA fusion gene was
      successfully constructed and expressed in M15 as the inclusion body after induced
      with IPTG. All the target proteins expressed could bind the PSMA antigen.
      CONCLUSION: Fusion proteins can specifically bind the PSMA antigen. This finding
      contributes to the study of the targeted delivery of siRNA.

PMID- 25597171
TI  - [Impact of morphine on the reproductivity of male rats].
AB  - OBJECTIVE: To explore the effect of morphine on male reproductive ability and its
      mechanisms in the rat model of morphine tolerance. METHODS: Twenty male SD rats
      were equally randomized to groups I (control) and II (morphine tolerance). On the
      1st day, the basic paw withdrawal thermal latency (PWTL) was obtained from all
      the rats followed by subcutaneous injection of morphine at 10 mg/kg and then
      calculation of the percentage of the maximal possible effect (MPE) at 30 min
      after administration. On the 2nd day, the rats of group I were injected
      subcutaneously with saline and those of group I with morphine at 10 mg/kg bid for
      7 days. Then all the rats were killed after behavioral tests and their testes and
      epididymides harvested for sperm counting and determina- tion of the expressions
      of Bax and Caspase-3 by immunohistochemistry. RESULTS: On the 1st day, no obvious
      differences were ob- served between the two groups in the basic PWTL or the
      percentage of MPE. On the 7th day, the percentage of MPE was significantly
      decreased in group II as compared with group I (P < 0.05), while the basic PWTL
      showed no marked difference between the two groups. Group II also exhibited a
      significantly reduced epididymal perm count (P < 0.05) and remarkably upregulated
      expressions of Bax and Caspase-3 in comparison with group I. CONCLUSION: Morphine
      might increase testicular cell apoptosis and reduce sperm concentration by
      upregulating the expressions of Bax and Caspase-3 in the rat model of morphine
      tolerance.

PMID- 25597170
TI  - [Protective effect of epigallocatechin gallate against sperm abnormality in
      mice].
AB  - OBJECTIVE: To investigate the protective effect of epigallocatechin gallate
      (EGCG) on mouse sperm in vivo. METHODS: A total of 64 six-week-old male Kuming
      mice were randomly divided into eight groups of equal number to be treated with
      normal saline (negative control), Cyclophosphamide (CP) at 30 mg/kg (positive
      control), and CP followed by EGCG (experimental) at 20, 40, and 80 mg/kg,
      respectively, given every other day for 10 days. At 4 and 5 weeks after
      treatment, the bilateral testes of the mice were harvested for examination of
      sperm abnormality. RESULTS: EGCG did not increase the rate of CP-induced sperm
      abnormality in the mice, but reduced it instead with the prolonged time of
      treatment. CONCLUSION: EGCG protects mouse sperm in vivo.

PMID- 25597172
TI  - [Polymorphisms of DNA methyltransferases and the risk of prostate cancer].
AB  - OBJECTIVE: To investigate the relationship between the polymorphisms of DNA
      methyltransferase (DNMT) and the risk and pathologic characteristics of prostate
      cancer (PCa) in Chinese men. METHODS: This case-control study included 155 PCa
      patients and 155 healthy male controls. Using Sequenom MassARRAY, we detected the
      genotypes of the DNMT1 polymorphisms rs16999593 and rs2228611 and the DNMT3B
      polymorphism rs2424908, followed by analysis of their association with the risk
      and pathologic characteristics of prostate cancer by logistic regression.
      RESULTS: Significant differences were found in the frequency of the rs16999593
      genotypes (P = 0.041) and that of the rs2424908 genotypes (P = 0.025) between the
      case and control groups. The frequencies of the genotypes rs16999593CT (OR =
      0.61, 95% CI 0.38-0.99, P = 0.043) and rs16999593CT/CC (OR = 0.59, 95% CI 0.39
      0.92, P = 0.017) were obviously higher in the control than in the case group, and
      so were those of rs2424908CT (OR = 0.73, 95% CI 0.58-0.91, P = 0.007) and
      rs2424908CT/CC (OR = 0.57, 95% CI 0.36-0.94, P = 0.023). The frequencies of
      rs16999593CT/CC (OR = 0.47, 95% CI 0.28-0.85, P = 0.008) and rs2424908CT/CC (OR =
      0.46, 95% CI 0.28-0.85, P = 0.009) were evidently lower in the cases with Gleason
      score < 7 than in the controls. However, none of the three polymorphisms ex
      hibited any significant differences in the frequencies of their genotypes between
      the patients with Gleason score > 7 and the healthy con trols (P > 0.05).
      CONCLUSION: The rs16999593CT/CC genotype of DNMT1 and the rs2424908CT/CC genotype
      of DNMT3B are as sociated with decreased risk of prostate cancer and lower
      Gleason score in C.

PMID- 25597173
TI  - [Efficacy and safety of vitamin D in the treatment of idiopathic
      oligoasthenozoospermia].
AB  - OBJECTIVE: To explore the efficacy and safety of vitamin D (VD) in the treatment
      of idiopathic oligoasthenozoospermia. METHODS: This study included 86 infertile
      men with idiopathic oligoasthenozoospermia, who were randomized to a VD and a
      control group of equal number, the former given oral VD 200 IU/d and calcium 600
      mg/d,qd, while the latter administered oral vitamin E 100 mg and vitamin C 100
      mg, tid. After 3 months of medication, we compared the semen parameters, adverse
      reactions, and pregnancy rate between the two groups. RESULTS: After medication,
      the count of progressively motile sperm per ejaculate was increased from (9.82 +/
      3.72) x 10(6) to (21.47 +/- 6.52) x 10(6) ( P < 0.05) and the proportion of
      progressively motile sperm from (18.41 +/- 9.82)% to (28.27 +/- 4.47)% (P < 0.05)
      in the VD group. In comparison, the count of progressively motile sperm per
      ejaculate was elevated from (9.51 +/- 6.31) x 10(6) to (12.36 +/- 4.43) x 10(6)
      (P > 0.05) and the proportion of progressively motile sperm from (17.79 +/-
      5.25)% to (21.35 +/- 2.41)% (P > 0.05) in the control group. Pregnancy was
      achieved in 7 cases (16.3%) in the VD group, but only lease (2.3%) in the control
      (P < 0.05). No adverse reactions were observed in either of the groups.
      CONCLUSION: Vitamin D, as a safe option for the treatment of idiopathic
      oligoasthenozoospermia, can effectively improve the semen quality, especially the
      progressive sperm motility of the patient.

PMID- 25597174
TI  - [Physical exercise improves erectile function in young and middle-aged men].
AB  - OBJECTIVE: To assess the association between physical exercise and erectile
      function in young and middle-aged men. METHODS: Using Paffenbarger Physical
      Activity Questionnaire (PPAQ) and IIEF-15, we conducted an investigation among 30
      to 45-year-old male outpatients at the clinic of urology. Based on the physical
      activity described in PPAQ, the patients were divided into a sedentary group (<=
      1,400 Kcal/wk) and an exercise group (> 1,400 Kcal/wk). RESULTS: The total score
      on IIEF-15 was signifi- cantly higher in the exercise group than in the sedentary
      group (62.2 vs 54.4), and so were the scores on the domains of erectile func-
      tion (26.4 vs 23.3), sexual desire (7.8 vs 6.9), orgasmic function (9.0 vs 8.3),
      intercourse satisfaction (11.5 vs 9.6), and overall satisfaction (7.5 vs 6.3)
      (all P < 0.05). CONCLUSION: Increased physical activity is associated with better
      sexual function in young and middle-aged men.

PMID- 25597175
TI  - [Expression of serum FSTL-1 in bone metastasis of prostate cancer and its
      clinical implication].
AB  - OBJECTIVE: To investigate the expression of follistatin-like protein 1 (FSTL-1)
      in bone metastasis of prostate cancer (BMPC), the correlation of serum FSTL-1
      with the chronic inflammatory factor interleukin-6 (IL-6) and bone morphogenetic
      protein 6 (BMP6) , and the clinical application value of serum FSTL-1 in BMPC.
      METHODS: Using ELISA, we measured the expression levels of serum FSTL-1, IL-6,
      and BMP6 in 35 patients with BMPC and another 30 with benign prostatic
      hyperplasia (BPH) and performed correlation analysis on the data obtained.
      RESULTS: Compared with the BPH controls, the BMPC patients showed a significantly
      decreased expression of serum FSTL-1 ([34.45 +/- 12.35] MUg/L vs [20.23 +/- 8.69]
      MUg/L, P < 0.01) and increased levels of IL-6 ([11.21 +/- 8.62] MUg/L vs [23.56
      +/- 20.12] MUg/L, P < 0.05) and BMP6 ([293.50 +/- 39.72] MUg/L vs [428.30 +/-
      178.40] MUg/L, P < 0.05). There was a significant negative correlation between
      the level of serum FSTL-1 and those of IL-6 and BMP6 in the BMPC patients, with
      correlation coefficients of -0.971 and -0.972, respectively (P < 0.05).
      CONCLUSION: The expression of serum FSTL-1 decreases in patients with bone
      metastasis of prostate cancer, and it is correlated with the levels of
      inflammatory factor and cell transformation factor. This finding offers a novel
      biological marker for the development and progression of prostate cancer as well
      as a new biological target factor for its intervention.

PMID- 25597176
TI  - [Adjuvant hormonal therapy immediately after radical surgery for high-risk organ
      confined or locally advanced prostate cancer].
AB  - OBJECTIVE: To evaluate the effect of adjuvant hormonal therapy (AHT) immediately
      after radical surgery for high- risk organ-confined or locally advanced prostate
      cancer using the PSA-related biochemical relapse rate within 2 years after
      surgery. METHODS: We retrospectively analyzed 62 cases of high-risk organ
      confined or locally advanced prostate cancer. The patients were treated by
      laparoscopic radical prostatectomy or radical retropubic prostatectomy after MRI
      and ECT systemic bone imaging examination, which revealed no regional lymph node
      or bone metastasis. Thirty-two of the patients (group A) received AHT orally or
      subcutaneously from 2 weeks to 1 months after operation, and another 30 (group B)
      were left untreated. We followed up the patients for 2 years, measuring the serum
      PSA level every 3 months, performing ECT every 6 months, and recording the
      adverse reactions, medication dura- tion, and the patients'quality of life.
      RESULTS: All the operations were successfully accomplished. The rate of 2-year
      biochemical relapse-free survival was 78.13% (25/32) in group A and 53.33%
      (16/30) in group B. CONCLUSION: AHT immediately after radical surgery can improve
      the rate of biochemical relapse-free survival of the patients with high-risk
      organ-confined or locally advanced prostate cancer and check the progression and
      metastasis of the disease.

PMID- 25597177
TI  - [IL-6 and sICAM-1 in seminal plasma relate to male immune infertility].
AB  - OBJECTIVE: To detect the expressions of interleukin-6 (IL-6) and soluble
      intercellular adhesion molecule-1 (sI- CAM-1) in the seminal plasma of infertile
      men and explore the role of inflammatory cytokines in male immune infertility.
      METHODS: Based on the results of the sperm-bound antibody immunobead test, 123
      males with clinically suspected infertility were divided into an immune
      infertility group (n = 41), other infertility group A (n = 37), and other
      infertility group B (n = 45). The immune infertility patients were further
      subdivided into a leukocyte-positive and a leukocyte-negative group according to
      the results of leukocyte peroxidase staining. The control group included 31 males
      confirmed to be fertilein the clinic. Statistical analyses were conducted on the
      differences in inflammatory cytokines expressions and main parameters in the
      seminal plasma among different groups. The seminal liquefaction time was measured
      by visual and microscopic observation, sperm concentration and motility detected
      using the computer-assisted sperm analysis system, sperm viability determined by
      hypotonic swelling assay, and the expression levels of IL-6 and sICAM-1 meas-
      ured by ELISA. RESULTS: The infertility groups showed significantly lowers perm
      viability (P < 0.05) and progressive motility (P < 0.01) than the fertile
      control, but no remarkable differences from the latter in sperm concentration (P
      > 0.05) and semen liquefaction time (P > 0.05). No statistically significant
      differences were observed in seminal parameters between the immune infertility
      group and other infertility groups (P > 0.05). The IL-6 and sICAM-1 levels in the
      seminal plasma were extremely significantly higher in the im- mune infertility
      group ([37.92 +/- 17.01] ng/L and [89.15 +/- 41.82] ng/ml), other infertility
      group A ([22.23 +/- 13.77] ng/L and [67.81 +/- 33.24] ng/ml), and other
      infertility group B ([18.75 +/- 14.32] ng/L and [53.25 +/- 27.09] ng/ml) than in
      the normal control group ([9.47 +/- 5.76] ng/L and [19.46 +/- 9.77] ng/ml) (P
      <0.01) , with remarkable differences between the immune infertility group and the
      other two infertility groups (P < 0.05). The leukocyte-positive patients showed
      significantly increased levels of IL-6 ([49.25 +/- 21.46] ng/L) and sICAM-1
      ([104.36 +/- 46.41] ng/ml) as compared with the leukocyte-negative ones ([31.38
      +/- 15.54] ng/Land [80.38 +/- 35.52] ng/ml) (both P < 0.05). CONCLUSION: IL-6 and
      sICAM-1 in the seminalplasma are involved in male immune infertility.

PMID- 25597178
TI  - [Therapeutic efficacy of Bushengzhuyang Fang (Yangjing Capsule) on phytoestrogen
      induced erectile dysfunction: an experimental study].
AB  - OBJECTIVE: To investigate the effect of Bushengzhuyang Fang (Yangjing Capsule,
      YJC) on penile erectile function and its action mechanisms in rats. METHODS:
      Fifty-six male SD rats were randomly divided into seven groups of equal number:
      blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein
      + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The
      rats in the blank control group were treated intragastrically with normal saline
      and those in the other groups with daidzein at the dose of 100 mg per kg per day
      for 30 days. Then the last five groups received additionally testosterone (4 mg
      per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per
      kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26
      mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed
      the apomorphine-induced spontaneous erectile response and pathological changes in
      the corpus cavernosum of the rats, recorded the number of penile erection and
      erectile incubation period, and determined the serum levels of testosterone (T)
      and luteinizing hormone (LH). RESULTS: At 30 days of treatment, the number of
      apomorphine-induced erections was decreased, the erectile incubation period
      prolonged, and the serum levels of T and LH reduced remarkably in all groups of
      rats (P < 0.05). Compared with the findings at 30 days, the number of penile
      erections was significantly decreased at 60 days in the daidzein group (1.39 +/-
      0.42 vs 2.67 +/- 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 +/- 0.49
      vs 2.83 +/- 0.61, P < 0.05); the erectile incubation period was markedly ex-
      tended ([16.33 +/- 3.11] vs [8.50 +/- 0.93] min and [15.50 +/- 3.21] vs [8.63 +/-
      1.54] min, P < 0.05); and the serum levels of T ([5.34 +/- 0.89] vs [1.24 +/-
      0.30] ng/ml and [5.28 +/- 1.12] vs [2.07 +/- 0.76] ng/ml, P < 0.05) and LH ([3.62
      +/- 0.37] vs [2.09 +/- 0.12] ng/ml and [3.79 +/- 0.28] vs [2.17 +/- 0.33] ng/ml,
      P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC
      groups, respectively. Pathological examination revealed slightly decreased
      cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the
      daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and
      daidzein + high-dose YJC groups as compared with those in the blank control
      group. CONCLUSION: High-dose Yangjing Capsule is efficacious for the recovery of
      erectile function in rats, especially for phytoestrogen-induced erectile
      dysfunction.

PMID- 25597179
TI  - [Efficacy and safety of Longjintonglin Capsule for the treatment of type III
      prostatitis].
AB  - OBJECTIVE: To study the therapeutic effect and safety of Longjintonglin Capsule
      in the treatment of type III prostatitis (chronic prostatitis/chronic pelvic pain
      syndrome, CP/CPPS). METHOD: We selected 240 patients with type III prostatitis
      according to the diagnostic standards of the American National Institute of
      Health (NIH) and treated them with Longjintonglin Capsule orally 3 capsules once
      tid for 12 weeks. Based on the NIH chronic prostatitis symptom index (NIH-CPSI),
      traditional Chinese medicine (TCM) syndrome score, and leukocyte count in the
      expressed prostatic secretion (EPS), we evaluated the results of treatment.
      RESULTS: Totally 238 patients completed the treatment, including 108 IIIA and 120
      III B prostatitis cases. Before and after 4, 8, and 12 weeks of treatment, the
      total NIH-CPSI scores were 23.12 +/- 6.99, 18.22 +/- 6.39, 14.12 +/- 5.88, and
      12.36 +/- 6.04 (P < 0.01) in the IIIA prostatitis patients and 22.01 +/- 6.28,
      17.56 +/- 5.89, 13.67 +/- 5.18, and 11.45 +/- 5.22 in the III prostatitis
      patients (P < 0.01), the TCM syndrome scores were 52.12 +/- 13.08, 48.13 +/-
      12.11, 43.05 +/- 11.19, and 40.78 +/- 10. 59 in the former (P < 0.01) and 53.02
      +/- 12.12, 49.32 +/- 12.78, 44.01 +/- 11.79, and 39.67 +/- 10.26 in the latter (P
      < 0.01), and the leukocyte counts were 26.09 +/- 21.55, 23.02 +/- 18.61, 18.25 +/
      17.79, and 15.36 +/- 16.38 in the IIIA cases (P < 0.01). Neither abnormalities
      in liver and renal function nor obvious adverse events were observed during the
      experiment. CONCLUSION: Longjintonglin Capsule, with its advantages of safety,
      effectiveness, and no obvious adverse reactions in the treatment of type III
      prostatitis, deserves to be recommended for clinical application.

PMID- 25597180
TI  - [No-flip method versus external method for Shang Ring circumcision: a meta
      analysis].
AB  - OBJECTIVE: To compare the effect and safety of the no-flip method versus the
      external method in Shang Ring circumcision. METHODS: We searched relevant
      randomized controlled trials published in China and abroad comparing the no-flip
      method and external method of Shang Ring circumcision. Based on the Cochrane
      Handbook for systematic review, two reviewers independently eval- uated the
      quality of the included studies and abstracted relevant data, followed by a meta
      analysis using the statistical software Review Manager 5.1.0. RESULTS: Totally 7
      studies with 1 200 cases were included. Compared with the external method, the no
      flip method was associated with a lower total rate of complications (RR = 0.40,
      95% CI: 0.18, 0.87, P = 0.02), a lower incidence of postop- erative edema (RR =
      0.28, 95% CI: 0.09, 0.81, P = 0.02), and a lower 24 h postoperative pain score
      (MD = -0.35, 95% CI: -0.55, -0.14, P < 0.001). CONCLUSION: The no-flip method of
      Shang Ring circumcision was superior to the external method for its advantages of
      fewer complications, lower incidence of postoperative edema, and mild
      postoperative pain. However, our findings need further support by more high
      quality randomized controlled trials.

PMID- 25597181
TI  - [Characteristics of complex chromosomal rearrangement in Chinese male carriers
      and its impact on male fertility].
AB  - OBJECTIVE: To analyze the characteristics of complex chromosomal rearrangement
      (CCR) in Chinese male carriers and its influence on male fertility. METHODS:
      Using the G band technique, we conducted karyotype analysis on the peripheral
      blood lymphocytes of 1,625 Chinese males with reproductive problems. We also
      searched CNKI and Wanfang database for CCR-related literature published between
      January 1984 and November 2013, followed by statistical analysis on the CCR
      characteristics and reproduction-related data of the CCR carriers. RESULTS: Two
      CCR carriers were found among the 1,625 males and another 47 cases identified
      from the databases. Among the 49 CCR carriers, there were 17 three-way exchange
      cases (34.7%), 17 double two-way exchange cases (34.7%), and 15 exceptional cases
      (30.6%), with no statistically significant differences in the incidence of the
      three types (P > 0.05). Azoospermia- or oligospermia-induced infertility was
      found in 19 (38.8% ) of the CCR carriers. A total of 87 pregnancies were achieved
      in the other 30 (61.2%), among which spontaneous abortion occurred in 75.9%
      (66/87), dead fetus and malformed infant death in 9.2% (8/87), and phenotypically
      normal offspring in 14.9% (13/87). Recurrent abortion was associated frequently
      with breakpoints on CCR-involved chromosomes 6, 7, 8, 11, and 16, while
      dyszoospermia mostly with breakpoints on CCR-involved chromosomes 10 and 14. The
      breaking occurred more than 3 times at 1p22, 1q25, 2q31, 5p13, 5q35, 6q23, 8q13,
      and 20p13. Moreo- ver, the breakpoints at 2q31, 5q35, and 8q13 were particularly
      related to recurrent abortion, while that at 1p22 only to dyszoospermia.
      CONCLUSION: CCR is extremely rare. Male CCR carriers are often identified through
      reproductive problems and have high risks of infertility and abnormal pregnancy
      and a very low rate of normal newborns. In addition, chromosomes and breakpoints
      involved in CCR may affect the fertility of male CCR carriers, and some
      particular chromosomal breakpoints may play a key role in gametogenesis.

PMID- 25597182
TI  - [Roles of pericytes in the urological and reproductive systems].
AB  - Pericyte, also known as mural cell or Rouget cell, is one of the main cells that
      make up the wall of capillaries. Pericytes play important roles not only in the
      maturation, stability, and function maintenance of blood vessels, but also in the
      growth and development of tissues and organs, wound repair, and other
      physiological and pathological processes. Researches on the functions of
      pericytes are mainly concentrated on their multipotency, adjustment of vascular
      functions, and process of fibrosis, as well as on renal fibrosis, renal blood
      flow regulation, and glomerular filtration in urology, but are quite insufficient
      in andrology. This article reviews the location, origin, distribution,
      morphology, markers, and functions of pericytes, aiming to induce further studies
      of pericytes in andrology.

PMID- 25597183
TI  - [Pathogenesis of premature ejaculation: a neurobiological approach].
AB  - Premature ejaculation (PE) is a most common male sexual dysfunction with complex
      pathogenesis. An increasing number of scholars agree that PE is a disorder
      associated with abnormal neurobiology, which involves the central
      neurotransmitter system, peripheral nerve function of the nerve tissue structure,
      and neurological biochemistry. This review focuses on the neurobiological
      mechanisms of PE, expecting to gain a deeper insight into the possible etiology,
      objective and reliable diagnostic methods, and individualized treatment of the
      disease.

PMID- 25597184
TI  - [Updated treatment of castration-resistant prostate cancer].
AB  - Most prostate cancer cases ultimately relapse after a period of initial response
      to castration therapy and progress to intractable castration-resistant prostate
      cancer (CRPC). Hardly any therapeutic options currently used can improve the 2-
      to 3-year survival of the patient. Recently, some new drugs for the treatment of
      CRPC through various action mechanisms have been approved, and others are in the
      advanced stage of clinical trial. This review provides an overview of these new
      therapeutic agents.

PMID- 25597186
TI  - Characterization of methicillin-resistant Staphylococcus spp. isolated from dogs
      in Korea.
AB  - Staphylococci were isolated from dogs in animal hospitals, animal shelters, and
      the Daegu PET EXPO to investigate the characteristics of circulating methicillin
      resistant Staphylococcal (MRS) strains in companion animals in Korea. A total of
      36/157 isolates were classified as MRS, and subdivided as follows: 1 methicillin
      resistant Staphylococcus aureus (MRSA), 4 methicillin-resistant Staphylococcus
      epidermidis, 2 methicillin-resistant Staphylococcus haemolyticus, and 29 MRS spp.
      Among the 36 MRS isolates tested, 100% were resistant to oxacillin and
      penicillin, and at least 50% were resistant to sulfamethoxazole/trimethoprim
      (69.4%), erythromycin (63.9%), tetracycline (58.3%), cefoxitin (55.6%),
      clindamycin (50.0%) or pirlimycin (50.0%). Additionally, 34/36 MRS isolates
      (94.4%) were mecA positive, 15 of which were further classified as SCCmec type V,
      6 isolates as type I, 4 isolates as type IIIb, 1 isolate as type IVa, 1 isolate
      as type IV, with 7 isolates being non-classifiable. The results of multilocus
      sequence typing and spa typing for the one MRSA strain were ST 72 (1-4-1-8-4-4-3)
      and spa t148. Our results provide evidence that companion animals like dogs may
      be MRS carriers, and that continued surveillance of MRS in companion animals is
      required to prevent increased incidences in humans.

PMID- 25597185
TI  - Olfactory ensheathing cells (OECs) degrade neurocan in injured spinal cord by
      secreting matrix metalloproteinase-2 in a rat contusion model.
AB  - The mechanism by which olfactory ensheathing cells (OECs) exert their potential
      to promote functional recovery after transplantation into spinal cord injury
      (SCI) tissue is not fully understood, but the relevance of matrix
      metalloproteinases (MMPs) has been suggested. We evaluated the expression of MMPs
      in OECs in vitro and the MMP secretion by OECs transplanted in injured spinal
      cord in vivo using a rat SCI model. We also evaluated the degradation of
      neurocan, which is one of the axon-inhibitory chondroitin sulfate proteoglycans,
      using SCI model rats. The in vitro results showed that MMP-2 was the dominant MMP
      expressed by OECs. The in vivo results revealed that transplanted OECs secreted
      MMP-2 in injured spinal cord and that the expression of neurocan was
      significantly decreased by the transplantation of OECs. These results suggest
      that OECs transplanted into injured spinal cord degraded neurocan by secreting
      MMP-2.

PMID- 25597187
TI  - Quantification of contamination levels and particular risk of Salmonella spp. in
      pigs in slaughterhouses in Chiang Mai and Lamphun provinces, Thailand.
AB  - Salmonella spp. is one of the important foodborne pathogens, and the slaughtering
      process is recognized as a potential point of contamination and the spread of the
      pathogens. The three objectives of this study are first, to quantify the
      contamination levels of Salmonella spp. in pig skins and carcasses, second, to
      evaluate the outcomes from different pig supply sources and different practices
      at three critical steps (scalding, splitting, and washing) for Salmonella spp.
      contamination, and third, to assess risk of Salmonella spp. contamination in pork
      products after slaughtering level. The study was performed in three
      representative slaughterhouses in Chiang Mai and Lamphun provinces, Thailand.
      Investigation conducted from May 2013 through October 2013 found the overall
      prevalence and contamination levels mean to be 11.85% and 0.34 MPN/cm2,
      respectively. There was no statistically significant in Salmonella spp.
      prevalence and contamination levels detected with different patterns at the
      slaughterhouses which were supplied pigs from either co-operative or integrated
      farms. Factors found to reduce Salmonella spp. loads on carcasses included good
      practices, e.g., regular changing of water in the scalding tank after each batch
      and the use of chlorine in the washing step. Risk of Salmonella spp.
      contamination of pork products at the final stage of slaughtering was nearly 10%.
      Good practices and proper hygiene measures should be applied to minimize the risk
      of Salmonella spp. exposure in the slaughtering line, which can reduce the
      contamination pressure downstream at retail shops as well as for end consumers.

PMID- 25597188
TI  - Natural A(H1N1)pdm09 influenza virus infection case in a pet ferret in Taiwan.
AB  - Ferrets have demonstrated high susceptibility to the influenza virus. This study
      discusses a natural 2009 pandemic influenza A (H1N1) (A(H1N1)pdm09) virus
      infection in a pet ferret (Mustela putorius furo) identified in Taiwan in 2013.
      The ferret was in close contact with family members who had recently experienced
      an influenza-like illness (ILI). The ferret nasal swab showed positive results
      for influenza A virus using one-step RT-PCR. The virus was isolated and the
      phylogenetic analysis indicated that all of the eight segmented genes were
      closely related to the human A(H1N1)pdm09 virus linage isolated in Taiwan. This
      study may provide a perspective view on natural influenza A virus transmission
      from the local human population into pet ferrets.

PMID- 25597189
TI  - Effects of ovarian storage condition on in vitro maturation of Hokkaido sika deer
      (Cervus nippon yesoensis) oocytes.
AB  - The effects of different preservation conditions (temperature 20-25 or 10-15
      degrees C; duration 12 or 24 h) for ovaries of Cervus nippon yesoensis on in
      vitro maturation of oocytes were examined. When ovaries were kept for 12 h at 20
      25 degrees C, maturation rate of oocytes was highest (71%); however, it declined
      when the preservation time was extended to 24 h (31%). When the preservation
      temperature decreased to 10-15 degrees C, the maturation rate after 12 h
      preservation decreased (51%) but it remained in same level even though
      preservation time is prolonged to 24 h (55%).

PMID- 25597190
TI  - Management of the pulp in primary teeth--an update.
AB  - Management of the pulpal tissue in primary teeth is a clinical challenge facing
      dental practitioners on a regular basis. This article reviews the most common
      treatments used at the present time in the management of the pulp in deciduous
      teeth. It gives an overview of treatment options and the indications and contra
      indications for the different treatment modalities. The evidence behind the
      medicaments used, their actions and success rates are discussed. Practical
      guidelines for choosing to retain or extract deciduous teeth and management of
      the primary tooth pulp with different clinical presentations are discussed. Areas
      of future research are highlighted.

PMID- 25597191
TI  - Master file size and apical transportation in severely curved root canals.
AB  - OBJECTIVES: A curvature leads to asymmetrical removal of root dentine, which
      results in an increase in the incidence of canal transportation. The aim of this
      study was to evaluate the effect of master apical file (MAF) size on the apical
      transportation (AT) of teeth with severe canal curvatures. METHODS: Thirty-six
      mesial roots of human mandibular first molars were included. Inclusion criteria
      consisted of mature roots with closed apices, absence of carious lesions and
      resorptions, and root canal curvatures (CC) of 45 degrees < CC < 60 degrees. The
      root canals were prepared using a crown-down pressureless technique. The samples
      were equally divided into groups A, B, and C based on MAF size: group A: MAF size
      equivalent to #20; group B: MAF size equivalent to #25, and group C: MAF size
      equivalent to #30. Cone beam computed tomography was used to evaluate the AT.
      RESULTS: There were no statistically significant differences in the AT between
      the canals with different curvature angles up to MAF size #30 (P = 0.55).
      CONCLUSION: Using flexible hand files for canal preparation, an increase in MAF
      size up to #30 does not significantly influence AT in severely curved canals.

PMID- 25597192
TI  - Integrating patient reported outcomes and other emerging methods into evidence
      based dentistry.

PMID- 25597193
TI  - Oral health of older people admitted to hospital for needs assessment.
AB  - OBJECTIVES: To describe the clinical oral health status, treatment needs and oral
      health-related quality of life (OHRQoL) of older people admitted to older
      persons' wards at Dunedin Public Hospital due to a sudden worsening of their
      general health. Participants and methods: A systematic oral assessment was
      undertaken for a consecutive case series of 200 patients (59.5% female; mean age
      82.6 years, sd 6.6) admitted to older person's wards at Dunedin Public Hospital.
      The Oral Health Impact Profile-20 (OHIP-20) was used to assess OHRQoL. RESULTS:
      One in three (36.0%) had been living independently at home prior to admission,
      and over half (55.0%) had been admitted for a medical reason which required
      assessment. Half (50.0%) of the participants were dentate (with an average of
      16.8 teeth). There was an average of 1.9 decayed teeth present in the dentate
      group; 70.7% of individuals required restorations or extractions, and about 90%
      required only simple scaling of the teeth and prophylaxis. A reline or a
      replacement denture were required by three-quarters of those with dentures.
      Almost two-thirds of participants did not have a regular dentist, and fewer than
      one in three had made a dental visit in the previous year. One in six described
      their oral health as 'fair' or 'poor', and just under one-third reported dry
      mouth. Dentate participants, those without xerostomia, and those reporting better
      oral health had better OHRQoL, reflected in lower OHIP-20 scores. Affecting 37.1%
      of participants, functional limitation was the most commonly experienced of the
      OHIP-20 domains, followed by physical disability and physical pain (18.0% and
      15.6% respectively). CONCLUSIONS: The oral health of medically compromised and
      functionally dependent but cognitively competent older people in this study is
      generally poor. If transfer to long-term care is indicated, early and proper
      preventive measures and appropriate dental contact should be advocated in order
      to reduce morbidity and improve quality of life for older people.

PMID- 25597194
TI  - Microstructural analysis of Co-Cr dental alloy at the metal-porcelain interface:
      a pilot study.
AB  - OBJECTIVE: The purpose of the study was to observe whether conventional porcelain
      firings had an effect on the underlying microstructure of cobalt-chromium alloys
      used in porcelain-fused-to-metal systems. METHODS: One as cast (non-veneered) and
      two porcelain veneered Co-Cr specimens layered with and without tungsten(W)-metal
      conditioner were manufactured and analysed. Electron backscatter diffraction was
      used to determine the crystal structures and grain size across the porcelain
      fused-to-metal interface. RESULTS: No difference was found in the microstructure
      of the alloy in both with and without W-metal conditioner. For the porcelain
      fired specimens, disparately sized granular structures were observed adjacent to
      the metal-porcelain interfaces compared to the bulk of the metal. Ellipsoid
      shaped grains at the alloy surface ranged between 1-11 MUm in diameter and
      averaged 2.70 MUm (SD: 2.17 MUm) for the specimen layered with W-metal
      conditioner and 2.86 MUm (SD: 1.85 MUm) for the specimen layered without W-metal
      conditioner. Grains located in the bulk were > 200 MUm with dendritic-like
      features. The depth of the fine grain structure adjacent to the surface had an
      average depth of 15 MUm. The crystal structure of the surface layer was found to
      be predominantly hexagonal close-packed whereas the underlying bulk was a mixture
      of both face-centered cubic and hexagonal close-packed phases. For the as cast
      specimen, similar large grains of over 200 MUm was observed but exhibited no
      dendritic like features. In addition, no fine grains were observed at the surface
      region of the as cast alloy. CONCLUSION: Conventional porcelain firings altered
      the interfacial and bulk microstructure of the alloy while the presence of the W
      metal conditioner had no influence on the underlying alloy microstructure.

PMID- 25597195
TI  - William F Throp 1917-2014.

PMID- 25597197
TI  - Second-hand smoke in the home more harmful than air pollution.

PMID- 25597198
TI  - Improving the management of asthma in adults in primary care.
AB  - Studies in adult patients have suggested that 30% of those diagnosed with asthma
      do not have the condition and it is likely that the diagnosis is missed in many
      others. Initial clinical assessment should explore symptoms of wheeze,
      breathlessness, chest tightness and cough. The probability of asthma is increased
      if more than one of these symptoms is present and particularly if symptoms are
      worse at night and in the early morning or are exacerbated by triggers such as
      exercise, allergen exposure, cold air or drugs. The BTS/SIGN guideline advocates
      spirometry after taking the history. If airflow obstruction is present, a trial
      of treatment can commence, but a firm diagnosis also requires a symptomatic
      response and an improvement in the measured airflow obstruction. The FeNO level
      correlates well with airway inflammation, and is therefore a good indicator of
      asthma and in particular of the likely response to inhaled corticosteroids. The
      test is especially useful for patients with suggestive symptoms but normal
      spirometry. The cornerstone of asthma monitoring is a structured clinical review
      conducted in primary care on at least an annual basis. Health outcomes are
      improved by education in self-management, incorporating written personalised
      asthma action plans. Checking concordance with existing therapies and inhaler
      technique before escalating treatment is an important part of improving the
      pharmacological management of asthma. Any patient prescribed more than one short
      acting bronchodilator device a month should be identified and have their asthma
      assessed urgently and measures taken to improve overall control.

PMID- 25597199
TI  - Early diagnosis pivotal to survival in lung cancer.
AB  - The UK has been highlighted, by the International Cancer Benchmarking Project and
      the EUROCARE groups, as a country with one of the lowest lung cancer survival
      rates. It has been postulated that this is due to an excess of early deaths,
      delays in diagnosis are thought to contribute to this problem. A recent study
      showed that 30% of patients with lung cancer die within the first 90 days and
      they have seen their GP on average five times in the four months before
      diagnosis, suggesting there may be opportunities to diagnose these patients
      earlier in the disease process. The challenge GPs face is to identify and refer
      those at risk as early as possible and to maintain a high index of suspicion if
      symptoms persist. The SIGN guideline reiterates the importance of performing a
      chest X-ray in those in whom the suspicion of lung cancer has been raised and not
      to be falsely reassured by a normal chest X-ray in a high-risk patient. The
      initial investigation of choice in secondary care remains a CT scan of the chest
      and abdomen, followed by PET-CT scanning in those deemed suitable for potentially
      curative treatment. Smoking cessation reduces the risk of post-operative and
      systemic treatment-related complications and also reduces the chance of cancer
      recurrence. Surgery remains the initial treatment of choice for those with early
      stage disease in NSCLC who are deemed fit enough. Those who have early stage
      NSCLC (stage I or stage II) who are either medically inoperable or decline
      surgery should be offered radical radiotherapy. Hospital follow-up should be
      continued while patients are receiving treatment, complemented by clinical nurse
      specialist input alongside community support. All patients should have access to
      specialist palliative care teams. Those with palliative care input have improved
      quality of life and symptom control and fewer hospitalisations.

PMID- 25597200
TI  - GPs could play key role in prostate cancer survivorship programmes.
AB  - The number of men living with prostate cancer in the UK is predicted to rise from
      255,000 to 416,000 in 2020 and 620,000 by 2030. More than 80% of men diagnosed
      with prostate cancer can expect to survive for at least five years. Up to 87% of
      men with prostate cancer may have unmet supportive care needs. Patients regularly
      cite psychological and sexual issues as the most significant. Poor functional
      outcomes after treatment such as incontinence and erectile dysfunction have a
      major impact on quality of life. The traditional model of hospital follow-up
      fails to deliver optimum patient-centred cancer care. Holistic aspects of care
      such as psychological needs and factors which may facilitate full rehabilitation
      of patients back into society may be missed. The key elements of a survivorship
      programme are: education, intervention, surveillance and co-ordination of care.
      Interventions which may improve immediate care include: structured holistic needs
      assessment and care planning, treatment summaries and cancer care reviews,
      patient education and support events and advice about, and access to, physical
      activity schemes. Urologists and GPs need to collaborate to establish shared care
      pathways for prostate cancer patients. Elements of these innovative pathways will
      include clear follow-up protocols for prostate cancer survivors discharged into
      the community and rapid access arrangements for patients about whom GPs are
      concerned.

PMID- 25597201
TI  - Hand conditions.

PMID- 25597202
TI  - Outbreak of milk-borne diphtheria. 1914.

PMID- 25597203
TI  - Why do doctors and patients speak a different language?

PMID- 25597204
TI  - Sonographic evaluation of the plantar fascia in asymptomatic subjects.
AB  - PURPOSE: To evaluate the appearance of the plantar fascia in asymptomatic
      subjects. MATERIALS AND METHODS: Thirty-one asymptomatic subjects were examined
      by 2 musculoskeletal radiologists. The plantar fascia was evaluated for
      thickness, echogenicity, vascularity on power Doppler, rupture, fluid adjacent to
      the fascia, andcalcifications. RESULTS: The study included 14 men and 17 women
      (age, 17-79 years; mean, 45 years). The mean thickness of the plantar fascia in
      men was 3.7 mm (range 2.5-7 mm), and in women 3.5 mm (range, 1.7-5.1 mm). The
      thickness was greater than 4 mm in 4 men (bilateral in 2). The mean thickness of
      fascias thicker than 4 mm in men was 5.4 mm (range, 4.3-7 mm). The thickness was
      greater than 4 mm in 5 women ( bilateral in 4). The mean thickness of fascias
      thicker than 4 mm in women was 4.7 mm (range, 4.2-5.1 mm). There was no
      statistically significant difference between men and women and between both
      heels. Hypoechogenicity was observed in 3 men (bilateral in 2), and in 5 women
      (bilateral in 6). Hypervascularity, rupture, fluid adjacent to the fascia, and
      calcifications were not observed. CONCLUSION: A thickness greater than 4 mm and
      hypoechogenicity, are common in the plantar fascia of asymptomatic subjects.
      Findings that were not seen in asymptomatic subjects include a thickness greater
      than 7 mm, hypervascularity on power Doppler, rupture, fluid adjacent to the
      fascia, and calcifications.

PMID- 25597205
TI  - Giant cavernous malformations in young adults: report of two cases, radiological
      findings and surgical consequences.
AB  - Cerebral cavernous malformations, also known as cavernous angioma or cavernoma,
      are a type of vascular disorder. They consist of abnormally large vascular
      cavities or sinusoid channels of varying size. The majority of cavernous
      malformations in the brain are small and do not always present with symptoms. A
      minority of large cavernous malformations, known as giant cavernous malformations
      (GCM), can cause neurological symptoms (such as headaches, focal neurologic
      deficits and seizures), which are probably related to hemorrhage and mass effect.
      GCM grow steadily in size over time, due to repetitive episodes of bleeding. The
      purpose of this paper is to document two case reports of patients with GCM,
      illustrate the radiological appearance, discuss the neurosurgical consequences,
      and to provide a literature analysis.

PMID- 25597206
TI  - Multidetector computed tomography diagnosis of gastric volvulus through the
      foramen of Morgagni.
AB  - Morgagni hernia is considered to be the rarest form of all diaphragmatic hernias.
      It develops through a congenital defect in the retrosternal area. Usually
      asymptomatic, this entity can lead to life-threatening complications such as
      incarceration, strangulation or volvulus of the herniated viscus. We hereby
      report a rare case of organoaxial gastric volvulus producing through the foramen
      of Morgagni in a 78-year-old woman. The full diagnosis was made by upper gastro
      intestinal series and multidetector computed tomography (MDCT). The basic
      anatomy, physiopathology, diagnostic methods, complications and surgical
      treatment of Morgagni hernia are briefly reviewed.

PMID- 25597207
TI  - Amyloidosis: an unusual cause of mesenteric, omental and lymph node
      calcifications.
AB  - We present a rare case of amyloidosis initially presenting with giant calcified
      inguinal adenopathy. Further imaging revealed diffuse calcifications within the
      mesentery and greater omentum. Amyloid deposition may mimic chronic granulomatous
      disorders and primary or secondary neoplastic conditions. Although definite
      diagnosis is made on histology, the radiologist should include amyloidosis in the
      differential diagnosis in the absence of a clinical history of neoplastic
      disorders or chronic infection, especially if extensive intra- lesional
      calcifications are seen. Ultrasound may be useful to target solid noncalcified
      areas in easily accessible extra- abdominal locations.

PMID- 25597208
TI  - Spontaneous rupture: a rare complication of hepatic hemangiomas.
AB  - Hepatic lesions are one of the possible visceral causes of spontaneous
      hemoperitoneum. Hepatic hemangiomas are congenital vascular malformations and are
      the most common benign tumours of the liver. Most cases are asymptomatic.
      Although they seldom rupture, it is important to diagnose them as their global
      mortality rate is high. An accurate diagnosis of a hemangioma as cause of a
      hemoperitoneum would result in correct clinical decision making and treatment.

PMID- 25597209
TI  - Granular cell tumor in the breast mimicking breast carcinoma.
AB  - Granular cell tumor is also known as a granular cell myoblastoma, Abrikossoff's
      tumor, granular cell nerve sheath tumor or granular cell scwhannoma. It is a rare
      soft-tissue mass that can develop in any soft tissue. Most commonly it appears in
      the tongue (40%), the oral cavity or in the subcutaneous tissue. In rare
      occasions it is reported as a breast mass, mimicking a carcinoma. Not only
      clinically, but also on mammography, ultrasonography and macroscopically.
      Diagnosis can only be made on histology, emphasizing once again the importance of
      a thorough pre-operative multi-disciplinary assessment. We describe a case in
      which a woman presents herself with a palpable nodule in the breast in which
      clinical investigation, mammography and especially sonography indicated the
      presence of a malignancy. Only after we conducted a core biopsy for pre-operative
      histological investigation, we could make the diagnosis of a granular cell tumor,
      preventing an unnecessary mastectomy. The patient refused however local excision
      and was followed up with mammography and sonography.

PMID- 25597210
TI  - Correlative imaging in gallbladder carcinoma.
AB  - Gallbladder carcinoma is a relatively rare malignant epithelial neoplasm, arising
      from gallbladder mucosa. It is the fifth most common gastrointestinal malignancy
      and the most common biliary tract cancer. Early diagnosis remains difficult,
      because clinical symptoms are sparse and non-specific, often resulting in
      advanced stage disease at the time of diagnosis. The most common feature of
      gallbladder carcinoma on different imaging modalities is focal wall thickening,
      associated with a large eccentric tumor mass. In this case we report the imaging
      characteristics of gallbladder carcinoma on ultrasound, MDCT and 18F-FDG PET/CT.

PMID- 25597211
TI  - Axial osseous lesions mimicking disseminated metastases, a report of osseous
      mastocytosis.
AB  - This article reports a case of osseous mastocytosis, a relatively rare pathology
      that shows nonspecific osteolytic and osteoblastic bone lesions on CT. As
      metastatic disease is the most frequent pathology that results in incidentally
      discovered diffuse osteoblastic lesions, biopsy should be performed in case of
      doubt.

PMID- 25597212
TI  - Solitary fibrous tumor of the kidney.
AB  - Solitary fibrous tumor (SFT) is an unusual spindle cell neoplasm rarely described
      in the kidney. Usually occurring in the pleura, it has also been described in
      various extrapleural sites. We report a rare case of SFT of the kidney
      fortuitously found in a 55-year-old patient. The imaging features are
      illustrated. The definite diagnosis was made through histological and
      immunohistochemical study after radical nephrectomy.

PMID- 25597213
TI  - Mesenteric inflammatory myofibroblastic tumor: MRI and CT imaging correlated to
      anatomical pathology.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare tumor, classified by WHO of
      intermediate biological potential with tendency for local recurrence and small
      risk for distant metastasis. Histologically IMT is a mixture of inflamma- tory
      cells and myofibroblastic spindle cells proliferation. To our knowledge there is
      no MRI description of mesenteric IMT in the literature. We would like to
      emphasize the correlation between medical imaging and anatomical pathology based
      on our experience of a mesenteric IMT in a 28-year-old patient.

PMID- 25597214
TI  - Rapid malignant transformation of primary synovial chondromatosis into
      chondrosarcoma.
AB  - Chondrosarcoma of the synovium is rare. It may arise de novo from the synovium or
      pre-existing synovial chondro- matosis may undergo malignant transformation into
      chondrosarcoma. Diagnosing a malignant transformation of the synovium remains a
      big challenge. It is based on the correlation of clinical findings, imaging and
      histology, as illustrated in this case report.

PMID- 25597215
TI  - A rare case of early onset type of abdominal trocar site hernia (TSH) with
      atypical externalizing in two-step: multidetector row CT diagnosis.
AB  - We report a rare case of early onset type Trocar Site Hernia (TSH) producing in
      the right lower abdominal quadrant of a 64-year old obese woman. The patient was
      admitted in the emergency room for abdominal pain producing four days after
      laparoscopic adnexectomy. The hernia atypically externalized in two-steps
      creating two superposed concentric small bowel strangulating hernias producing
      through two distinctive superposed orifices. A precise and complete anatomic
      diagnosis was made by contrast enhanced 64-row multidetector computed tomography
      (MDCT). The imaging features are presented with a short review of the literature.
      The case emphasizes the high performances of MDCT for the early diagnosis of
      Trocar Site Hernias.

PMID- 25597216
TI  - Diffusion restriction of posterior uveal melanoma on MR imaging.

PMID- 25597217
TI  - Delayed onset muscle soreness.

PMID- 25597218
TI  - Idiopathic intracranial hypertension.

PMID- 25597219
TI  - Hemangioperiocytoma simulating meningioma in a 41-year-old man.

PMID- 25597220
TI  - Proximal avulsion fracture of the long head of the triceps brachii muscle.

PMID- 25597221
TI  - Secondary infertility caused by a midline cyst of the prostate.

PMID- 25597222
TI  - Lunate dislocation.

PMID- 25597223
TI  - Acute renal failure due to bilateral ureteral stone: a rare occurrence.

PMID- 25597224
TI  - There aren't plenty more fish in the sea: a causal network approach.
AB  - The current research investigated how lay representations of the causes of an
      environmental problem may underlie individuals' reasoning about the issue. Naive
      participants completed an experiment that involved two main tasks. The causal
      diagram task required participants to depict the causal relations between a set
      of factors related to overfishing and to estimate the strength of these
      relations. The counterfactual task required participants to judge the effect of
      counterfactual suppositions based on the diagrammed factors. We explored two
      major questions: (1) what is the relation between individual causal models and
      counterfactual judgments? Consistent with previous findings (e.g., Green et al.,
      1998, Br. J. Soc. Psychology, 37, 415), these judgments were best explained by a
      combination of the strength of both direct and indirect causal paths. (2) To what
      extent do people use two-way causal thinking when reasoning about an
      environmental problem? In contrast to previous research (e.g., White, 2008, Appl.
      Cogn. Psychology, 22, 559), analyses based on individual causal networks revealed
      the presence of numerous feedback loops. The studies support the value of
      analysing individual causal models in contrast to consensual representations.
      Theoretical and practical implications are discussed in relation to causal
      reasoning as well as environmental psychology. 

PMID- 25597225
TI  - Optimizing insulin pump therapy: the potential advantages of using a structured
      diabetes management program.
AB  - Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic
      control, reduces hypoglycemia and increases treatment satisfaction in individuals
      with diabetes. As a number of patient- and clinician-related factors can hinder
      the effectiveness and optimal usage of CSII therapy, new approaches are needed to
      address these obstacles. Ceriello and colleagues recently proposed a model of
      care that incorporates the collaborative use of structured SMBG into a formal
      approach to personalized diabetes management within all diabetes populations. We
      adapted this model for use in CSII-treated patients in order to enable the
      implementation of a workflow structure that enhances patient-physician
      communication and supports patients' diabetes self-management skills. We
      recognize that time constraints and current reimbursement policies pose
      significant challenges to healthcare providers integrating the Personalised
      Diabetes Management (PDM) process into clinical practice. We believe, however,
      that the time invested in modifying practice workflow and learning to apply the
      various steps of the PDM process will be offset by improved workflow and more
      effective patient consultations. This article describes how to implement PDM into
      clinical practice as a systematic, standardized process that can optimize CSII
      therapy. 

PMID- 25597226
TI  - Anti-sulfatide IgM antibodies in peripheral neuropathy: to test or not to test?
AB  - BACKGROUND AND PURPOSE: Anti-sulfatide immunoglobulin M (IgM) antibodies have
      been associated with different forms of neuropathies but their diagnostic role in
      neuropathy remains unclear. METHODS: The clinical association of increased titers
      of anti-sulfatide IgM antibodies in 570 patients with neuropathy and related
      disorders examined in our laboratory since 2004 was reviewed. Sera were tested by
      enzyme-linked immunosorbent assay at the initial serum dilution of 1:32,000 and
      titrated by serial two-fold dilution. In all positive patients IgM antibodies to
      myelin-associated glycoprotein (MAG) were also measured by western blot. RESULTS:
      High titers of anti-sulfatide antibodies were found in 39 patients including 33
      (85%) who also had anti-MAG IgM. Six patients did not have anti-MAG IgM including
      five in whom moderately increased anti-sulfatide titers were associated with
      different forms of neuropathy. One patient with a demyelinating neuropathy and
      IgM monoclonal gammopathy had markedly increased anti-sulfatide titers
      (1:256,000). CONCLUSIONS: Increased titers of anti-sulfatide IgM antibodies are
      not infrequent in patients with neuropathy where they are often associated with a
      concomitant reactivity to MAG. A selective reactivity to sulfatide, however, is
      rarely found and is associated with different forms of neuropathy limiting its
      usefulness in the diagnosis of neuropathy.

PMID- 25597227
TI  - Molecular and cellular approach in the study of antioxidant/pro-oxidant
      properties of Micromeria croatica (Pers.) Schott.
AB  - Phytochemical composition and antioxidant activity of three wild populations of
      endemic Illyric-Balcanic species Micromeria croatica (Pers.) Schott have been
      evaluated with respect to plant organ and growing location. Multivariate analysis
      (principal component analysis) was performed to visualise (dis-)similarity among
      samples and identify the correlations between phytochemical variables that
      explain the most variability. The tested leaf extract from BaCic kuk locality
      exhibited protective effects against reactive oxygen species-induced damage of
      DNA and inhibition of lipid peroxidation, while it caused oxidative degradation
      of protein in the bovine serum albumin assay at higher concentrations. This
      extract also exhibited cytotoxic activity and facilitated the formation of
      reactive oxygen species in the HEp2 cell line, in a dose-dependent manner. 

PMID- 25597228
TI  - Dual growth factor-immobilized microspheres for tissue reinnervation: in vitro
      and preliminary in vivo studies.
AB  - Growth factors (GFs) (basic fibroblast growth factor (bFGF) and/or nerve growth
      factor (NGF))-immobilized polycaprolactone (PCL)/Pluronic F127 microspheres were
      prepared using an isolated particulate-melting method and the sequential binding
      of heparin and GFs onto the microspheres. The GFs immobilized on the microspheres
      were released in a sustained manner over 28 days, regardless of GF type. From the
      in vitro culture of muscle-derived stem cells, it was observed that the NGF
      immobilized microspheres induced more neurogenic differentiation than the bFGF
      immobilized microspheres, as evidenced by a quantitative real-time polymerase
      chain reaction using specific neurogenic markers (Nestin, GFAP, beta-tubulin, and
      MAP2) and Western blot (Nestin and beta-tubulin) analyses. The dual bFGF/NGF
      immobilized microspheres showed better neurogenic differentiation than the
      microspheres immobilized with single bFGF or NGF. From the preliminary animal
      study, the dual bFGF/NGF-immobilized microsphere group also showed effective
      nerve regeneration, as evaluated by immunocytochemistry using a marker - beta
      tubulin. The dual bFGF/NGF-immobilized PCL/Pluronic F127 microspheres may be a
      promising candidate for nerve regeneration in certain target tissues (i.e.
      muscles) leading to sufficient reinnervation. 

PMID- 25597229
TI  - Letter to the editor.

PMID- 25597230
TI  - Complexation of allyl radicals and hydrochloric acid in helium nanodroplets.
AB  - Infrared spectra of the allyl radical-HCl complex in superfluid helium
      nanodroplets have been recorded in the IR frequency range of 2750-3120 cm(-1).
      Six fundamental bands were observed, five of which have been assigned to the C-H
      stretch vibrations of the allyl radical. No additional CH bands were observed
      upon the binding of HCl. The band at 2800.3 cm(-1) can unambiguously be assigned
      to the bound HCl stretch, which is red-shifted by 106 cm(-1) compared to that of
      the free HCl. Stark spectra and pickup curves were recorded and support our
      assignment. In accompanying ab initio calculations, we found four equivalent
      minima and computed a two-dimensional potential energy surface for the HCl
      positioning on the allyl radical plane at the CCSD(T)/TZVPP level. Based on our
      findings, we conclude that the ground-state structure of the complex shows two
      energetically equivalent T-shaped minimum structures. Because of small barriers
      between the two minima, a delocalization of the HCl is anticipated. 

PMID- 25597231
TI  - Finite element analysis for edge-to-edge technique to treat post-mitral valve
      repair systolic anterior motion.
AB  - Systolic anterior motion of the mitral valve is an uncommon complication of
      mitral valve repair, which requires immediate supplementary surgical action. Edge
      to-edge suture is considered as an effective technique to treat post-mitral valve
      repair systolic anterior motion by clinical researchers. However, the
      fundamentals and quantitative analysis are vacant to validate the effectiveness
      of the additional edge-to-edge surgery to repair systolic anterior motion. In the
      present work, finite element models were developed to simulate a specific
      clinical surgery for patients with posterior leaflet prolapse, so as to analyze
      the edge-to-edge technique quantificationally. The simulated surgery procedure
      concluded several actions such as quadrangular resection, mitral annuloplasty and
      edge-to-edge suture. And the simulated results were compared with
      echocardiography and measurement data of the patients under the mitral valve
      surgery, which shows good agreement. The leaflets model with additional edge-to
      edge suture has a shorter mismatch length than that of the model merely under
      quadrangular resection and mitral annuloplasty actions at systole, which assures
      a better coaptation status. The stress on the leaflets after edge-to-edge suture
      is lessened as well. 

PMID- 25597232
TI  - Electromyographically recorded patellar reflex in normotensive pregnant women and
      patients with preeclampsia.
AB  - OBJECTIVE: To define reference values of the patellar reflex in normotensive
      pregnant and postpartum women and to compare these with values in women with
      preeclampsia. DESIGN: Observational study. SETTING: University teaching hospital
      in the Netherlands. POPULATION: Normotensive non-pregnant women, pregnant women
      and preeclamptic women. METHODS: In normotensive pregnant women the patellar
      reflex was cross-sectionally recorded using surface electromyography at four time
      points during pregnancy and six to eight weeks postpartum. In non-pregnant
      normotensive women this was recorded once. Preeclamptic women were recorded
      during pregnancy and postpartum. MAIN OUTCOME MEASURES: Latency and amplitude of
      the compound muscle action potential of the patellar reflex. RESULTS: Latency and
      amplitude of the compound muscle action potential during normotensive pregnancies
      showed no changes compared with the non-pregnant state during reproductive age.
      Latency of the compound muscle action potential was increased in pregnancies with
      severe preeclampsia compared with normotensive pregnancies. These differences
      disappeared postpartum. CONCLUSIONS: During pregnancy, the patellar reflex can be
      assessed using surface electromyography. Latency and amplitude show no changes
      during normotensive pregnancies and are no different from the postpartum or non
      pregnant values. In severely preeclamptic women, latency is increased. The
      clinical value of this is limited.

PMID- 25597233
TI  - Quality of life and psychosocial impact of scarring and non-scarring alopecia in
      women.
AB  - BACKGROUND: Alopecia is a common dermatological condition with mostly cosmetic
      consequences that, nevertheless, has significant psychological and psychosocial
      impact. OBJECTIVE: To assess the impact of alopecia on quality of life and
      certain psychological domains and to compare it between scarring and non-scarring
      alopecia in Greek adult women. PATIENTS AND METHODS: Forty-four women, aged 18-70
      years, with scarring (n = 19) or non-scarring alopecia (n = 25) were recruited.
      All patients were evaluated by Dermatology Life Quality Index (DLQI), Hospital
      Anxiety and Depression Scale (HADS), Rosenberg Self-esteem Scale (RSES) and UCLA
      Loneliness Scale (UCLA-LS). RESULTS: Women with scarring alopecia had higher
      scores in DLQI, HADS and UCLA- LS and lower scores in RSES, compared to women
      with non-scarring alopecia. A statistically significant difference between the
      two groups was documented for DLQI (p = 0.0067), HADS (p = 0.0008), and HADS
      Anxiety (HADS-A) (p < 0.05) and HADS-Depression (HADS-D) (p < 0.01) subscales.
      CONCLUSIONS: The psychological burden is heavier and quality of life is more
      severely impaired among women with scarring alopecia compared with non-scarring
      alopecia, probably depicting the poorer prognosis of the former.

PMID- 25597234
TI  - T-stage and positive sentinel nodes ratio are the useful factors to predict non
      sentinel node metastasis in breast cancer patients with macro-metastasis in the
      sentinel node.
AB  - INTRODUCTION: Current guidelines recommend completion axillary lymph node
      dissection (cALND) in case of a sentinel lymph node (SN) metastasis larger than 2
      mm (macrometastasis). However in many patients of those, the non-sentinel lymph
      nodes (NSN) contain no further metastasis, indicating that axillary lymph node
      dissection provides no benefit. To identify cases who could have undergone
      omission of the ALND with confidence, we have retrospectively evaluated the
      predictive factors of NSN metastasis with positive macrometastasis in the SN.
      METHODS: This study was based on a retrospective database of 420 patients who
      underwent sentinel lymph node biopsy (SNB) for breast cancer, of whom 61 patients
      had SN macrometastasis intra- and postoperatively. We examined predictive factors
      of NSN involvement in 51 cases of these 61 patients who underwent cALND. All
      clinical and histological variables were analyzed according to NSN status, by
      using Mann-Whitney U test, univariate and multivariate logistic regression model.
      RESULTS: T stage and the proportion of involved SNs among all identified SNs (SN
      ratio) were correlated with NSN metastasis. Univariate and multivariate analysis
      showed that T stage and SN ratio were the independent predictive factor of NSN
      metastasis. The area under ROC curve for SN ratio was 0.71. The best cut off
      value of SN ratio was 0.667. Negative predictive value to NSN metastasis in cases
      with both T2 and more than 0.667 of SN ratio was 85.7%. CONCLUSION: In patients
      with invasive breast cancer and macrometastasis of SN, T stage and SN ratio were
      useful for prediction of NSN metastasis.

PMID- 25597235
TI  - Two-phase (low-dose) computed tomography is as effective as 4D-CT for identifying
      enlarged parathyroid glands.
AB  - BACKGROUND: Four-dimensional computed tomography (4D-CT) is often used for
      patients with primary hyperparathyroidism and non-definitive localization after
      Sestamibi scan (MIBI) and ultrasound (US), but may expose patients to unnecessary
      radiation, typically between 10 and 26 millisieverts (mSv). We hypothesize that a
      simpler two-phase CT protocol would have a similar sensitivity, specificity and
      accuracy to those published for 4D-CT, while exposing the patient to less
      radiation. METHODS: We reviewed 54 patients with primary hyperparathyroidism and
      non-definitive localization studies who had a two-phase CT between 2009 and 2012
      at our tertiary referral center. RESULTS: The mean radiation dose of two-phase CT
      over the course of the study was 5.2 mSv (range 3.5 mSv-9.1 mSv). Two-phase CT
      had a 77% (CI = 65%-86%) sensitivity and an 87% (CI = 73%-95%) specificity to
      lateralize enlarged parathyroid glands to the correct side of the neck and a 58%
      (CI = 45%-68%) sensitivity and 91% (CI = 83%-94%) specificity to localize
      parathyroid tumors to the correct quadrant of the neck. The overall accuracy of
      two-phase CT to lateralize enlarged parathyroids was 81% (CI = 73%, 88%) and the
      accuracy to localize enlarged parathyroids was 79% (CI = 73%, 84%). DISCUSSION:
      As a second line investigation two-phase CT has a similar sensitivity,
      specificity and accuracy to those published for 4D-CT in patients with non
      localized, enlarged parathyroids with less radiation exposure. Two-phase CT can
      help localize enlarged parathyroid glands not definitively identified using MIBI
      and US. CONCLUSION: Two-phase CT allows clinicians to accurately identify
      enlarged parathyroid glands while exposing the patient to less radiation than 4D
      CT.

PMID- 25597236
TI  - Drug-coated percutaneous balloon catheters.
AB  - Percutaneous transluminal angioplasty revolutionized coronary and peripheral
      revascularization. However, it is always accompanied by major drawbacks such as
      elastic recoil and neointimal hyperplasia. Percutaneous transluminal angioplasty
      along with bare metal stents reduced elastic recoil, but in-stent restenosis
      (ISR) and peripheral artery stenting remain problems. Drug-eluting stents
      addressed the issue of ISR, but late stent thrombosis and delayed
      endothelialization, along with longer dual antiplatelet therapy, are of concern.
      Non-stent-based delivery such as drug-coated balloons (DCBs) that can deliver
      drugs to inhibit ISR or to de novo lesions, are emerging at a rapid pace. DCBs
      carry an active drug and a nonpolymeric carrier molecule or excipient that
      enhance the bioavailability of the drug to the vessel wall. Preliminary studies
      of paclitaxel show sustained delivery is not required to inhibit proliferation of
      vascular smooth muscle cells, which leds to the development and evolution of
      DCBs. Recent clinical trials have been successful in mitigating ISR in coronary
      and peripheral arteries, but not in de novo lesions of coronary arteries.
      Clinical studies, although limited to date, show a promising future for DCBs. 

PMID- 25597238
TI  - Corneal cross-linking: engineering a predictable model.
AB  - Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA)
      light has become a viable treatment for keratoconus. In cases in which corneal
      transplant may have previously been a patient's primary treatment option, the
      results of CXL have varied from decreased progression of the disease to marked
      regression characterized by improvement in visual acuity. In addition, changes to
      the original protocol have been tested that include leaving the epithelium intact
      and increasing the UVA intensity while decreasing the exposure time. The
      variation in results and protocols underscores the need for a greater
      understanding of the procedure and its effects. Ideally, a complete definition of
      the effects of CXL will lead to patient-specific treatment through highly
      controlled delivery methods of riboflavin and UVA light and complete mathematical
      models for predicting the final shape and refractive effect of the cornea. Thus,
      in this review, we aimed to describe the current techniques for measuring the
      effect of CXL, with a focus on material property changes, while highlighting the
      challenge of engineering a predictable mathematical model of the procedure and
      the resulting clinical outcome. 

PMID- 25597239
TI  - Tissues reborn: fetal membrane-derived matrices and stem cells in orthopedic
      regenerative medicine.
AB  - The amniotic and chorionic membranes, as well as the stem cell populations
      contained within them, represent a widely available, versatile, and promising
      resource for use in numerous regenerative medicine applications. The primary
      focus of this review is to examine the use of the fetal membranes and/or their
      resident stem cell populations for regenerating orthopedic tissues. This
      discussion is prefaced by a brief synopsis of the structure, function, and
      biological properties of the extracellular matrix; embryological development; and
      a brief description of the distinct stem cell populations residing within the
      amniotic and chorionic membranes. Commercially available perinatal tissue
      allograft products available in the United States are reviewed, and a concise
      summary regarding the US Food and Drug Administration's current viewpoint on
      these technologies is provided. Concluding remarks regarding suggested future
      research directives for evaluating these tissues and stem cell sources in
      relation to orthopedic regenerative medicine applications also are presented. 

PMID- 25597240
TI  - Clinical applications of surgical adhesives and sealants.
AB  - In the United States and Europe, the number of topical adhesives, surgical
      sealants, and hemostats approved for use in the surgical setting is ever
      expanding although no single device fills all medical and surgical needs to
      replace sutures. As more surgical procedures are performed through laparoscopic
      and robotic approaches, these devices are becoming more important, and current
      research is focused on solving the limitations of conventional wound treatments.
      This review article discusses clinical applications of various biologically
      derived and synthetic products that are currently available to surgeons and those
      that are in development. 

PMID- 25597237
TI  - Tissue engineering approaches to heart repair.
AB  - The heart is a large organ containing many cell types, each of which is necessary
      for normal function. Because of this, cardiac regenerative medicine presents many
      unique challenges. Because each of the many types of cells within the heart has
      unique physiological and electrophysiological characteristics, donor cells must
      be well matched to the area of the heart into which they are grafted to avoid
      mechanical dysfunction or arrhythmia. In addition, grafted cells must be
      functionally integrated into host tissue to effectively repair cardiac function.
      Because of its size and physiological function, the metabolic needs of the heart
      are considerable. Therefore grafts must contain not only cardiomyocytes but also
      a functional vascular network to meet their needs for oxygen and nutrition. In
      this article we review progress in the use of pluripotent stem cells as a source
      of donor cardiomyocytes and highlight current unmet needs in the field. We also
      examine recent tissue engineering approaches integrating cells with various
      engineered materials that should address some of these unmet needs. 

PMID- 25597241
TI  - A perspective on the role and utility of haptic feedback in laparoscopic skills
      training.
AB  - Laparoscopic surgery is a minimally invasive surgical technique with significant
      potential benefits to the patient, including shorter recovery time, less
      scarring, and decreased costs. There is a growing need to teach surgical trainees
      this emerging surgical technique. Simulators, ranging from simple "box" trainers
      to complex virtual reality (VR) trainers, have emerged as the most promising
      method for teaching basic laparoscopic surgical skills. Current box trainers
      require oversight from an expert surgeon for both training and assessing skills.
      VR trainers decrease the dependence on expert teachers during training by
      providing objective, real-time feedback and automatic skills evaluation. However,
      current VR trainers generally have limited credibility as a means to prepare new
      surgeons and have often fallen short of educators' expectations. Several
      researchers have speculated that the missing component in modern VR trainers is
      haptic feedback, which refers to the range of touch sensations encountered during
      surgery. These force types and ranges need to be adequately rendered by
      simulators for a more complete training experience. This article presents a
      perspective of the role and utility of haptic feedback during laparoscopic
      surgery and laparoscopic skills training by detailing the ranges and types of
      haptic sensations felt by the operating surgeon, along with quantitative studies
      of how this feedback is used. Further, a number of research studies that have
      documented human performance effects as a result of the presence of haptic
      feedback are critically reviewed. Finally, key research directions in using
      haptic feedback for laparoscopy training simulators are identified. 

PMID- 25597242
TI  - Role of vascularity for successful bone formation and repair.
AB  - Tissue engineering has been touted as the solution to regenerate tissue in
      patients. Yet current strategies for orthopedic application are limited because
      of the inability to successfully manage critical sized defects without a working
      vascular system. Bone grafts are commonly used in critical sized defects to fill
      the gap in missing bone tissue. Proper vasculature is vital to the success of
      these grafts to promote bone growth. The aim of this review is to describe the
      contribution of tissues surrounding critical sized defects, focusing in
      particular on the progenitor cell influx and factors contributing to
      neovascularization. An overview of clinical techniques to visualize patient
      vascular supply and evaluation of clinical techniques to increase blood flow to
      the critical defect site illustrates the current efforts of surgical intervention
      to promote proper bone formation. The opportunity and need lies in the
      development of tissue engineered bone grafts that can use and enhance available
      vascular supplies. 

PMID- 25597244
TI  - Genetic and environmental influence on the association between testosterone, sex
      hormone-binding globulin and body composition in Korean men.
AB  - OBJECTIVES: This study aimed to evaluate an association between testosterone, sex
      hormone-binding globulin and body composition as well as the influence of genetic
      and environmental factors on the association. DESIGN: A cross-sectional study.
      SETTING: Community-based study. PARTICIPANTS: One thousand and eighty-three
      Korean men including 144 pairs of monozygotic twins. MAIN OUTCOME MEASURE: Levels
      of serum total testosterone (TT) and sex hormone-binding globulin (SHBG) were
      measured by chemiluminescence immunoassay, and free testosterone (cFT) was
      calculated using Vermeulen's method. Detailed body composition was measured using
      dual-energy X-ray absorptiometry. We performed linear mixed regression analysis
      with consideration of familial correlations and covariates. RESULTS: Each 1-SD
      increase in age-adjusted levels of TT, cFT and SHBG was associated with lower
      levels of adiposity measures and absolute measures of lean body mass. On the
      other hand, percentage total lean mass increased with increasing levels of TT,
      cFT and SHBG (P < 0.05). Bivariate variance-component analyses revealed that most
      body composition measures had a significant inverse unique environmental
      correlation with both TT and SHBG, and a significant genetic correlation with TT.
      A co-twin control study in monozygotic twins showed that within-pair differences
      in adiposity measures were inversely associated with within-pair differences in
      the levels of TT and SHBG, while within-pair differences in lean mass were
      inversely associated with within-pair differences in the levels of TT.
      CONCLUSIONS: The significant associations of body composition with testosterone
      and SHBG were influenced by both genetic and environmental factors. Further
      efforts to elucidate related genes and modifiable environmental factors are
      needed.

PMID- 25597243
TI  - Magnetic resonance imaging of stem cell apoptosis in arthritic joints with a
      caspase activatable contrast agent.
AB  - About 43 million individuals in the U.S. encounter cartilage injuries due to
      trauma or osteoarthritis, leading to joint pain and functional disability. Matrix
      associated stem cell implants (MASI) represent a promising approach for repair of
      cartilage defects. However, limited survival of MASI creates a significant
      bottleneck for successful cartilage regeneration outcomes and functional
      reconstitution. We report an approach for noninvasive detection of stem cell
      apoptosis with magnetic resonance imaging (MRI), based on a caspase-3-sensitive
      nanoaggregation MRI probe (C-SNAM). C-SNAM self-assembles into nanoparticles
      after hydrolysis by caspase-3, leading to 90% amplification of (1)H MR signal and
      prolonged in vivo retention. Following intra-articular injection, C-SNAM causes
      significant MR signal enhancement in apoptotic MASI compared to viable MASI. Our
      results indicate that C-SNAM functions as an imaging probe for stem cell
      apoptosis in MASI. This concept could be applied to a broad range of cell
      transplants and target sites. 

PMID- 25597245
TI  - The acute effects of alcohol on sleep electroencephalogram power spectra in late
      adolescence.
AB  - BACKGROUND: Alcohol's effect on sleep electroencephalogram (EEG) power spectra
      during late adolescence is of interest given that this age group shows both
      dramatic increases in alcohol consumption and major sleep-related developmental
      changes in quantitative EEG measures. This study examined the effect of alcohol
      on sleep EEG power spectra in 18- to 21-year-old college students. METHODS:
      Participants were 24 (12 female) healthy 18- to 21-year-old social drinkers.
      Participants underwent 2 conditions: presleep alcohol and placebo, followed by
      standard polysomnography with comprehensive EEG recordings. RESULTS: After
      alcohol, mean breath alcohol concentration at lights-out was 0.084%. Interaction
      effects indicated simultaneous increases in frontal non-rapid eye movement sleep
      (NREM) delta (p = 0.031) and alpha (p = 0.005) power in the first sleep cycles
      following alcohol consumption which was most prominent at frontal scalp sites (p
      < 0.001). A decrease in sigma power (p = 0.001) was also observed after alcohol.
      CONCLUSIONS: As hypothesized, alcohol increased slow wave sleep-related NREM
      delta power. However, there was a simultaneous increase in frontal alpha power.
      Results suggest that alcohol may exert an arousal influence which may compete
      with the sleep maintenance influence of increased delta activity. The phenomenon
      is similar to, or the same as, alpha-delta sleep which has been associated with
      the presence of disruptive stimuli during sleep. This may have negative
      implications for the impact of presleep alcohol consumption on sleep and
      consequent daytime functioning.

PMID- 25597247
TI  - Down-regulation of the A3 adenosine receptor in human mast cells upregulates
      mediators of angiogenesis and remodeling.
AB  - Adenosine activated mast cells have been long implicated in allergic asthma and
      studies in rodent mast cells have assigned the A3 adenosine receptor (A3R) a
      primary role in mediating adenosine responses. Here we analyzed the functional
      impact of A3R activation on genes that are implicated in tissue remodeling in
      severe asthma in the human mast cell line HMC-1 that shares similarities with
      lung derived human mast cells. Quantitative real time PCR demonstrated
      upregulation of IL6, IL8, VEGF, amphiregulin and osteopontin. Moreover, further
      upregulation of these genes was noted upon the addition of dexamethasone.
      Unexpectedly, activated A3R down regulated its own expression and knockdown of
      the receptor replicated the pattern of agonist induced gene upregulation. This
      study therefore identifies the human mast cell A3R as regulator of tissue
      remodeling gene expression in human mast cells and demonstrates a heretofore
      unrecognized mode of feedback regulation that is exerted by this receptor. 

PMID- 25597248
TI  - Multifocal and multicentric breast cancer is associated with increased local
      recurrence regardless of surgery type.
AB  - Multifocal and multicentric breast cancers have been correlated with poor
      prognostic factors and worse outcomes versus unifocal disease. We evaluated the
      impact of multifocal and multicentric disease versus case controls with unifocal
      disease, matching for age, grade, T-, and N-stage. A total of 110 patients with
      multifocal (n = 93) or multicentric (n = 17) disease and 263 matched case
      controls were identified with a median follow-up of 53 months and 64 months,
      respectively. The actuarial local control rates for the multifocal/multicentric
      and unifocal group were 88% and 97%, respectively at both 5 and 10 years (p <
      0.001). On multivariate analysis, multifocal/multicentric disease remained
      associated with higher local recurrence after controlling for other covariates
      including surgery type. The disease-free survival rates in the
      multifocal/multicentric group at 5 and 10 years were 75% and 71%, respectively,
      versus 87% and 78% at 10 years (p = 0.01). On multivariate analysis,
      multifocal/multicentric disease was no longer associated with worse disease-free
      survival. There was no difference in the cohorts in terms of regional control,
      overall survival, or cancer specific survival. Our findings suggest that
      multifocal/multicentric disease may be associated with worse outcomes versus
      unifocal disease regardless of type of surgery. This suggests a more biologically
      aggressive cancer and may be an important consideration when managing these
      patients. Further studies are needed to better understand the impact of
      multifocal/multicentric breast cancers on outcomes.

PMID- 25597249
TI  - Diagnostic evaluation of the infertile male: a committee opinion.
AB  - The purpose of this ASRM Practice Committee report is to provide clinicians with
      principles and strategies for the evaluation of couples with male infertility
      problems. This revised document replaces the document of the same name, last
      published in 2012 (Fertil Steril 2012;98:294-301). 

PMID- 25597246
TI  - Desialylation of airway epithelial cells during influenza virus infection
      enhances pneumococcal adhesion via galectin binding.
AB  - The continued threat of worldwide influenza pandemics, together with the yearly
      emergence of antigenically drifted influenza A virus (IAV) strains, underscore
      the urgent need to elucidate not only the mechanisms of influenza virulence, but
      also those mechanisms that predispose influenza patients to increased
      susceptibility to subsequent infection with Streptococcus pneumoniae. Glycans
      displayed on the surface of epithelia that are exposed to the external
      environment play important roles in microbial recognition, adhesion, and
      invasion. It is well established that the IAV hemagglutinin and pneumococcal
      adhesins enable their attachment to the host epithelia. Reciprocally, the
      recognition of microbial glycans by host carbohydrate-binding proteins (lectins)
      can initiate innate immune responses, but their relevance in influenza or
      pneumococcal infections is poorly understood. Galectins are evolutionarily
      conserved lectins characterized by affinity for beta-galactosides and a unique
      sequence motif, with critical regulatory roles in development and immune
      homeostasis. In this study, we examined the possibility that galectins expressed
      in the airway epithelial cells might play a significant role in viral or
      pneumococcal adhesion to airway epithelial cells. Our results in a mouse model
      for influenza and pneumococcal infection revealed that the murine lung expresses
      a diverse galectin repertoire, from which selected galectins, including galectin
      1 (Gal1) and galectin 3 (Gal3), are released to the bronchoalveolar space.
      Further, the results showed that influenza and subsequent S. pneumoniae
      infections significantly alter the glycosylation patterns of the airway
      epithelial surface and modulate galectin expression. In vitro studies on the
      human airway epithelial cell line A549 were consistent with the observations made
      in the mouse model, and further revealed that both Gal1 and Gal3 bind strongly to
      IAV and S. pneumoniae, and that exposure of the cells to viral neuraminidase or
      influenza infection increased galectin-mediated S. pneumoniae adhesion to the
      cell surface. Our results suggest that upon influenza infection, pneumococcal
      adhesion to the airway epithelial surface is enhanced by an interplay among the
      host galectins and viral and pneumococcal neuraminidases. The observed
      enhancement of pneumococcal adhesion may be a contributing factor to the observed
      hypersusceptibility to pneumonia of influenza patients. 

PMID- 25597250
TI  - Geriatric oral health predicaments in New Delhi, India.
AB  - OBJECTIVES: The aim of the present study was to analyze geriatric oral health
      predicaments in India. Specifically, to assess the oral health status and
      treatment needs among the geriatric population attending health camps in New
      Delhi, Northern India. METHODS: The sample size for the cross-sectional study
      comprised of 248 elderly participants aged 60 years having attended the health
      check-up camps organized in New Delhi, India. The community periodontal index was
      used for assessment of periodontal disease. The World Health Organization's
      criterion was used for detection of dentition status and treatment needs. The
      chi(2) -test was used to compare between categorical variables. The Mann-Whitney
      U-test was used to compare between two groups for quantitative variables.
      Regression analysis was carried out to identify the factors associated with
      dental caries and periodontal disease status. RESULTS: The mean number of
      affected sextants with the highest community periodontal index score of 4 was
      3.54 +/- 2.45. Mean decayed, missing and filled teeth score of 16.39 +/- 8.97 was
      recorded among the elderly. Prosthetic need was noted among 206 (83.1%)
      participants. Age and literacy status contributed to 27% and 12% of the variance
      respectively in the decayed, missing and filled teeth model. (P < 0.001) Major
      contributory factors in the periodontal disease model for the 37%, 11% and 11%
      variance were age, sex and tobacco consumption (P < 0.001). CONCLUSION: Two
      striking features of the study were the high levels of unmet prosthetic needs and
      the extremely low utilization of dental care. There is an urgent necessity to
      resolve the high burden of unmet prosthetic need among the aged in India.

PMID- 25597251
TI  - Improved planning of endoscopic sinonasal surgery from 3-dimensional images with
      Osirix(r) and stereolithography.
AB  - INTRODUCTION AND OBJECTIVES: The high variability of sinonasal anatomy requires
      the best knowledge of its three-dimensional (3D) conformation to perform surgery
      more safely and efficiently. The aim of the study was to validate the utility of
      Osirix(r) and stereolithography in improving endoscopic sinonasal surgery
      planning. METHODS: Osirix(r) was used as a viewer and Digital Imaging and
      Communications in Medicine (DICOM) 3D imaging manager to improve planning for 114
      sinonasal endoscopic operations with polyposis (86) and chronic rhinosinusitis
      (CRS) (28). Stereolithography rapid prototyping was used for 7 frontoethmoidal
      mucoceles. RESULTS: Using Osirix(r) and stereolithography, a greater number of
      anatomical structures were identified and this was done faster, with a
      statistically-significant clinical-radiological correlation (P<.01) compared with
      2D CT plates. With a share of more than 75% of surgery performed by residents,
      surgical time was reduced by 38+/-12.3min in CRS and 42+/-27.9 in sinonasal
      polyposis. The fourth-year residents reached 100% surgical competence in critical
      surgical milestones with 16 surgeries (CI 12-19). CONCLUSIONS: The systematic use
      of Osirix(r) for visualisation and treatment of 3D sinonasal images from DICOM
      data files, along with the surgical team's ability to manipulate them as virtual
      reality, allows surgeons to perform endoscopic sinonasal surgery with greater
      confidence and in less time than using 2D images. Residents also achieve surgical
      competence faster, more safely and with fewer complications. This beneficial
      impact is increased when the surgical team has stereolithography rapid
      prototyping in more complex cases.

PMID- 25597252
TI  - Experience in cochlear reimplantation. Descriptive study of a 20-year period.
AB  - INTRODUCTION AND OBJECTIVES: The cochlear implant is a surgical procedure that
      has increased substantially, because the paediatric population is diagnosed and
      implanted early and because there are increased potential indications. This
      device has the inherent risk of failure in performance, as dies any active
      medical device, which is the most common cause of implant removal. Our goal was
      to understand what the causes that produced removal in our series were, and
      confirm if these conformed to reality as reviewed in the literature. METHODS:
      This was a retrospective, descriptive, observational study of 859 cochlear
      implant surgeries carried out between October 1991 and May 2011. The causes of
      implant removal were classified according to the European Consensus Statement on
      Cochlear Implant Failures and Explantations. RESULTS: The reimplantation rate was
      6.16% (n=51). The most common reason for removal was technical device failure
      (45.5%), followed by infection/rejection (23.6%) and upgrade (12.7%). Less common
      causes: there were 3 cases (5.6%) of electrode misplacement, 2 cases (3.6%) of
      labyrinthine ossification, 2 (3.6%) as a result of head trauma, 2 (3.6%) from
      need for nuclear magnetic resonance imaging and 1 case (1.8%) from psychiatric
      illness. CONCLUSIONS: Cochlear reimplantation is a safe procedure, with a low
      complication rate. In our centre, it reaches an overall rate of 6.16%. Technical
      device failure remains the most common cause of this procedure, although there is
      a significant percentage of reimplantation for device update.

PMID- 25597253
TI  - Secondary presentation of Mantle cell lymphoma in the subgaleal layer of the
      scalp.

PMID- 25597255
TI  - Dimerization of two alkyne units: model studies, intermediate trapping
      experiments, and kinetic studies.
AB  - By means of high level quantum chemical calculations (B2PLYPD and CCSD(T)), the
      dimerization of alkynes substituted with different groups such as F, Cl, OH, SH,
      NH2, and CN to the corresponding diradicals and dicarbenes was investigated. We
      found that in case of monosubstituted alkynes the formation of a bond at the
      nonsubstituted carbon centers is favored in general. Furthermore, substituents
      attached to the reacting centers reduce the activation energies and the reaction
      energies with increasing electronegativity of the substituent (F > OH > NH2, Cl >
      SH, H, CN). This effect was explained by a stabilizing hyperconjugative
      interaction between the sigma* orbitals of the carbon-substituent bond and the
      occupied antibonding linear combination of the radical centers. The formation of
      dicarbenes is only found if strong pi donors like NH2 and OH as substituents are
      attached to the carbene centers. The extension of the model calculations to
      substituted phenylacetylenes (Ph-C=C-Y) predicts a similar reactivity of the
      phenylacetylenes: F > OCH3 > Cl > H. Trapping experiments of the proposed
      cyclobutadiene intermediates using maleic anhydride as dienophile as well as
      kinetic studies confirm the calculations. In the case of phenylmethoxyacetylene
      (Ph-C=C-OCH3) the good yield of the corresponding cycloaddition product makes
      this cyclization reaction attractive for a synthetic route to cyclohexadiene
      derivatives from alkynes. 

PMID- 25597254
TI  - Reconstruction of oral cavity defects with FAMM (facial artery musculomucosal)
      flaps. Our experience.
AB  - INTRODUCTION AND OBJECTIVES: The facial artery musculomucosal (FAMM) flap is a
      good option for covering small and medium-sized defects in the oral cavity
      because of its similar tissue characteristics and easy implementation. METHODS:
      We reviewed our results using this flap between 2006 and 2014. A total of 20
      patients were included and 25 FAMM flaps were performed, 16 right (64%) and 9
      left (36%) flaps. Five patients had simultaneous bilateral reconstructions. The
      indications for flap surgery were reconstruction after resection of tumours in
      the floor of the mouth (8 cases, 40%), tumours in other sites of the oral cavity
      (4 cases, 20%), mandibular osteoradionecrosis (4 cases, 20%), oroantral fistula
      (3 cases, 15%) and postoperative ankyloglossia (one case, 5%). RESULTS:
      Reconstruction was successful in 92% of cases (n=23). Total flap necrosis
      occurred in one case and dehiscence with exposure of bone in another. Oral
      function and ingestion were satisfactory in all patients. CONCLUSIONS: The facial
      artery musculomucosal flap is reliable and versatile for reconstruction of small
      and medium-sized intraoral defects. It allows functional reconstruction of the
      oral cavity with a low risk of complications.

PMID- 25597256
TI  - [Could Ebola be an opportunity for health systems?].

PMID- 25597257
TI  - [History of malaria control in the French armed forces: from Algeria to the
      Macedonian front during the first World War].
AB  - The French joint military health corps has long experience in malaria control.
      Many military physicians played an essential role in the 19th century: Maillot
      revolutionized malaria treatment by using quinine during the conquest of Algeria,
      and Laveran discovered the causal parasite (the genus Plasmodium) there. This
      experience continued under the direction of Laveran and the Sergent brothers on
      the eastern front in Greek Macedonia during World War I. The vast coordinated
      control plan established on this front from 1917 delivered the French infantrymen
      from malaria and led to victory over the Bulgarian forces, which capitulated in
      September 1918. 

PMID- 25597258
TI  - [Intestinal parasites in prisoners in Ouagadougou (Burkina Faso)].
AB  - OBJECTIVES: to analyze the epidemiologic and clinical aspects of intestinal
      parasitosis in prisoners at the prison in Ouagadougou (MACO). MATERIALS AND
      METHODS: cross-sectional study from November 2009 to January 2010, including a
      survey to determine the risk factors and clinical signs of intestinal
      parasitosis. It also included laboratory examination of feces samples from 403
      prisoners, by direct analysis, the Willis and Ritchie methods, and a scotch test
      for oxyuris (Enterobios vermicularis). RESULTS: The global prevalence of
      intestinal parasitosis was 71.5%. There was a link between parasitism and the
      prison section. Amebae were the most frequent parasites (66.7%), with high
      prevalence of Entamoeba coli (55.6%). They were followed by flagellata (16.6%),
      mainly Trichomonas intestinalis (9.2%). Helminths were less frequent (7.4%). Most
      subjects with parasites were symptomatic (diarrhea or constipation) (p = 10(-4)).
      CONCLUSION: our results highlight the need to improve sanitation at the prison
      and provide hygiene education for the prison population.

PMID- 25597259
TI  - [Assessment of the completeness of medical imaging request forms in a sub-Saharan
      African setting].
AB  - The technical quality, interpretation, and clinical utility of diagnostic imaging
      examinations can increase considerably when the request forms are correctly
      filled out. This study sought to evaluate the completeness of these request forms
      at the Women and Children's Hospital in Yaounde, Cameroon, to the 8 criteria
      established by the French High Health Authority (HAS, France). METHODS: This
      cross-sectional study evaluated 118 request forms for ultrasounds, 110 for
      conventional radiography, and 34 for computed tomography (CT scans), all
      completed by physicians at our university-affiliated hospital. They were sampled
      consecutively three days a week for several weeks, on days randomly selected at
      the beginning of each week, to minimize bias and ensure that as many different
      physicians as possible were assessed. We doubled the sample size recommended by
      the HAS. Conformity was defined by the presence of the required data on the
      request forms (data classified as either administrative or clinical). RESULTS:
      Overall, 52 request forms (19.8%) had all 5 administrative items, but only 9.2%
      had all 3 clinical components. Only 3 forms (1.1%) were 100% complete, including
      all 8 items; 85% included at least 5 components, and 35.1% had 6. The patient's
      last name was always included. Only 4.2% of the request forms included the
      prescriber's telephone number; 8% did not include the date and 17.2% (n = 45) did
      not state the clinical findings. On 30% of the forms, symptoms were the only
      clinical information listed; 23.7% (n = 62) stated the purpose of the examination
      (that is, the diagnosis to be confirmed or ruled out). The rate of missing
      information was highest in the requests for conventional radiography (49.5%
      compared to 38% with ultrasound and 12.3% for CT scans). CONCLUSION: The request
      forms for imaging examinations provided inadequate administrative and clinical
      data, especially those for conventional radiography. This missing information
      makes it harder to perform and interpret these examinations. An electronic
      request form with mandatory fields might improve the overall quality of the
      forms.

PMID- 25597261
TI  - Abnormal sweating patterns associated with itching, burning and tingling of the
      skin indicate possible underlying small-fibre neuropathy.
AB  - BACKGROUND: Itching, burning, numbness and tingling of the skin are frequent
      reasons for dermatology consultation. We hypothesized that these sensations may
      be attributable to a small-fibre neuropathy. Sweating, which is mediated by small
      nerve fibres, may be a surrogate marker of small-fibre neuropathy. OBJECTIVES: To
      investigate the results of thermoregulatory sweat testing (TST), which depicts
      and estimates whole-body sweating, in patients with itching, burning, numbness
      and tingling sensations. METHODS: We retrospectively reviewed the medical records
      of 227 patients with itching, burning, numbness and tingling sensations involving
      the skin who were seen at our institution during 2008 and also underwent TST.
      RESULTS: The mean age of the cohort was 54 years (range 3-89), and 58% were
      female. In all, 149 patients (66%) had abnormal TST results; in 119 (80%) of
      these patients the areas of anhidrosis on TST corresponded to their symptomatic
      areas. For each symptom analysed separately, the area of anhidrosis correlated
      with the area of symptoms in most patients. CONCLUSIONS: Patients with burning,
      itching, numbness and tingling have abnormal sweating patterns and often do not
      sweat in the symptomatic areas. These novel findings suggest that a small-fibre
      neuropathy may underlie many cutaneous symptoms and that the neuropathy can be
      estimated using TST.

PMID- 25597260
TI  - An Exploration of Managers' Discourses of Workplace Bullying.
AB  - AIM: To identify discourses used by hospital nursing unit managers to
      characterize workplace bullying, and their roles and responsibilities in
      workplace bullying management. BACKGROUND: Nurses around the world have reported
      being the targets of bullying. These nurses often report that their managers do
      not effectively help them resolve the issue. There is scant research that
      examines this topic from the perspective of managers. METHODS: This was a
      descriptive, qualitative study. Interviews were conducted with hospital nursing
      unit managers who were recruited via purposive and snowball sampling. Data were
      analyzed using Willig's Foucauldian discourse analysis. RESULTS: Managers
      characterized bullying as an interpersonal issue involving the target and the
      perpetrator, as an intrapersonal issue attributable to characteristics of the
      perpetrator, or as an ambiguous situation. For interpersonal bullying, managers
      described supporting target's efforts to end bullying; for intrapersonal
      bullying, they described taking primary responsibility; and for ambiguous
      situations, they described several actions, including doing nothing. CONCLUSION:
      Managers have different responses to different categories of bullying. Efforts
      need to be made to make sure they are correctly identifying and appropriately
      responding to incidents of workplace bullying.

PMID- 25597262
TI  - Bovine Papillomavirus Type 13 Expression in the Urothelial Bladder Tumours of
      Cattle.
AB  - Bovine papillomavirus type 13 (BPV-13), a novel Deltapapillomavirus, has been
      found associated with urothelial tumours of the urinary bladder of cattle grazing
      on lands infested with bracken fern. BPV-13 was detected in 28 of 39 urothelial
      tumours. Diagnosis was based on sequencing of L1 and E5 amplicons from tumour
      samples. The nucleotide sequences generated from these amplicons showed a 100%
      homology with the sequences of BPV-13 L1 and E5 DNA found in Brazil from a
      fibropapilloma of the ear in a cow and from equine sarcoids in two horses.
      GenBank accession number of our representative BPV-13 sequences is JQ798171.1.
      Furthermore, mRNA encoding BPV-13 E5 oncoprotein was also documented, and its
      expression was also shown by immunohistochemistry and immunofluorescence in the
      basal and suprabasal urothelial tumour cells. In twenty-three tumours, BPV-13 was
      simultaneously found with BPV-2, a Deltapapillomavirus genus, species 4. The
      latter virus was detected by amplifying and sequencing a 154-bp-sized DNA
      fragment of BPV-2 E5. In addition, BPV-13 by itself was seen to be expressed in
      five BPV-2-negative urothelial tumours. This study shows that BPV-13 is present
      in urothelial tumour cells thus sharing biological properties with BPV-1 and BPV
      2. Although further studies are needed, BPV-13 appears to be another worldwide
      infectious agent responsible for a distressing disease causing severe economic
      losses in cattle industry.

PMID- 25597264
TI  - Cardioprotective cryptides derived from fish and other food sources: generation,
      application, and future markets.
AB  - The primary function of dietary protein is to provide amino acids for protein
      synthesis. However, protein is also a source of latent bioactive peptides or
      cryptides with potential health benefits including the control and regulation of
      blood pressure. Hypertension or high blood pressure is one of the major,
      controllable risk factors in the development of cardiovascular disease (CVD), and
      it is also implicated in the development of myocardial infarction, heart failure,
      and end-stage diabetes. Cryptides can act on various systems of the body
      including the circulatory, gastrointestinal (GI), nervous, skeletal, and
      respiratory systems. A number of studies carried out to date have examined the
      health benefits of food protein isolates and hydrolysates. This review provides
      an overview of existing blood pressure regulating peptides and products derived
      from fish and other protein sources and hydrolysates. It discusses the methods
      used currently to generate and identify cryptides from these sources and their
      application in food and pharmaceutical products. It also looks at the current
      market for protein-derived peptides and peptide-containing products, legislation
      governing their use, and the future development of research in this area.

PMID- 25597263
TI  - Quality of Disease Management and Risk of Mortality in English Primary Care
      Practices.
AB  - OBJECTIVE: To investigate whether better management of chronic conditions by
      family practices reduces mortality risk. DATA: Two random samples of 5 million
      patients registered with over 8,000 English family practices followed up for 4
      years (2004/5-2007/8). Measures of the quality of disease management for 10
      conditions were constructed for each family practice for each year. The outcome
      measure was an indicator taking the value 1 if the patient died during a
      specified year, 0 otherwise. STUDY DESIGN: Cross-section and multilevel panel
      data multiple logistic regressions were estimated. Covariates included age,
      gender, morbidity, hospitalizations, attributed socio-economic characteristics,
      and local health care supply measures. PRINCIPAL FINDINGS: Although a composite
      measure of the quality of disease management for all 10 conditions was
      significantly associated with lower mortality, only the quality of stroke care
      was significant when all 10 quality measures were entered in the regression.
      CONCLUSIONS: The panel data results suggest that a 1 percent improvement in the
      quality of stroke care could reduce the annual number of deaths in England by 782
      [95 percent CI: 423, 1140]. A longer study period may be necessary to detect any
      mortality impact of better management of other conditions.

PMID- 25597265
TI  - Curing profile of bulk-fill resin-based composites.
AB  - OBJECTIVE: To evaluate the curing profile of bulk-fill resin-based composites
      (RBC) using micro-Raman spectroscopy (MURaman). METHODS: Four bulk-fill RBCs were
      compared to a conventional RBC. RBC blocks were light-cured using a polywave LED
      light-curing unit. The 24-h degree of conversion (DC) was mapped along a
      longitudinal cross-section using MURaman. Curing profiles were constructed and
      'effective' (>90% of maximum DC) curing parameters were calculated. A statistical
      linear mixed effects model was constructed to analyze the relative effect of the
      different curing parameters. RESULTS: Curing efficiency differed widely with the
      flowable bulk-fill RBCs presenting a significantly larger 'effective' curing area
      than the fibre-reinforced RBC, which on its turn revealed a significantly larger
      'effective' curing area than the full-depth bulk-fill and conventional (control)
      RBC. A decrease in 'effective' curing depth within the light beam was found in
      the same order. Only the flowable bulk-fill RBCs were able to cure 'effectively'
      at a 4-mm depth for the whole specimen width (up to 4mm outside the light beam).
      All curing parameters were found to statistically influence the statistical model
      and thus the curing profile, except for the beam inhomogeneity (regarding the
      position of the 410-nm versus that of 470-nm LEDs) that did not significantly
      affect the model for all RBCs tested. CONCLUSIONS: Most of the bulk-fill RBCs
      could be cured up to at least a 4-mm depth, thereby validating the respective
      manufacturer's recommendations. CLINICAL SIGNIFICANCE: According to the curing
      profiles, the orientation and position of the light guide is less critical for
      the bulk-fill RBCs than for the conventional RBC.

PMID- 25597266
TI  - Two-year survival of ART restorations placed in elderly patients: A randomised
      controlled clinical trial.
AB  - OBJECTIVES: Older dentate adults are a high caries risk group who could
      potentially benefit from the use of the atraumatic restorative treatment (ART).
      This study aimed to compare the survival of ART and a conventional restorative
      technique (CT) using rotary instruments and a resin-modified glass-ionomer for
      restoring carious lesions as part of a preventive and restorative programme for
      older adults after 2 years. METHODS: In this randomised controlled clinical
      trial, 99 independently living adults (65-90 years) with carious lesions were
      randomly allocated to receive either ART or conventional restorations. The
      survival of restorations was assessed by an independent and blinded examiner 6
      months, 1 year and 2 years after restoration placement. RESULTS: Ninety-six
      (67.6%) and 121 (76.6%) restorations were assessed in the ART and CT groups,
      respectively, after 2 years. The cumulative restoration survival percentages
      after 2 years were 85.4% in the ART and 90.9% in the CT group. No statistically
      significant between group differences were detected (p=0.2050, logistic
      regression analysis). CONCLUSIONS: In terms of restoration survival, ART was as
      effective as a conventional restorative approach to treat older adults after 2
      years. This technique could be a useful tool to provide dental care for older
      adults particularly in the non-clinical setting. ( TRIAL REGISTRATION NUMBER:
      ISRCTN 76299321). CLINICAL SIGNIFICANCE: The results of this study show that ART
      presented survival rates similar to conventional restorations in older adults.
      ART appears to be a cost-effective way to provide dental care to elderly
      patients, particularly in out of surgery facilities, such as nursing homes.

PMID- 25597267
TI  - Assessment of swimming associated health effects in marine bathing beach: an
      example from Morib beach (Malaysia).
AB  - A survey among beachgoers was conducted to determine the swimming associated
      health effects experienced and its relationship with beach water exposure
      behaviour in Morib beach. For beach water exposure behaviour, the highest
      frequency of visit among the respondents was once a year (41.9%). For ways of
      water exposure, whole body exposure including head was the highest (38.5%). For
      duration of water exposure, 30.8% respondents prefer to be in water for about 30
      min with low possibilities of accidental ingestion of beach water. A total of
      30.8% of beachgoers in Morib beach were reported of having dermal symptoms.
      Bivariate analysis showed only water activity, water contact and accidental
      ingestion of beach water showed significant association with swimming associated
      health effects experienced by swimmers. This study output showed that
      epidemiological study can be used to identify swimming associated health effects
      in beach water exposed to faecal contamination.

PMID- 25597269
TI  - Morphology-modulation of SnO2 hierarchical architectures by Zn doping for glycol
      gas sensing and photocatalytic applications.
AB  - The morphology of SnO2 nanospheres was transformed into ultrathin nanosheets
      assembled architectures after Zn doping by one-step hydrothermal route. The as
      prepared samples were characterized in detail by various analytical techniques
      including scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), X-ray diffraction (XRD), and nitrogen adsorption-desorption technique. The
      Zn-doped SnO2 nanostructures proved to be the efficient gas sensing materials for
      a series of flammable and explosive gases detection, and photocatalysts for the
      degradation of methyl orange (MO) under UV irradiation. It was observed that both
      of the undoped and Zn-doped SnO2 after calcination exhibited tremendous gas
      sensing performance toward glycol. The response (S = Ra/Rg) of Zn-doped SnO2 can
      reach to 90 when the glycol concentration is 100 ppm, which is about 2 times and
      3 times higher than that of undoped SnO2 sensor with and without calcinations,
      respectively. The result of photocatalytic activities demonstrated that MO dye
      was almost completely degraded (~92%) by Zn-doped SnO2 in 150 min, which is
      higher than that of others (MO without photocatalyst was 23%, undoped SnO2
      without and with calcination were 55% and 75%, respectively).

PMID- 25597268
TI  - The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell
      invasion.
AB  - OBJECTIVE: Our objective was to investigate a miRNA pathway that acts downstream
      of VEGF-induced invasion of ovarian cancer cells. METHOD: We used two paired high
      and low metastatic serous ovarian cancer cells to demonstrate the role of miR-205
      in VEGF-induced invasion of ovarian cancer cells and to investigate the gene
      targets of miR-205. RESULTS: Our previous comparative proteomics studies showed
      that VEGF decreased the expression of Ezrin and Lamin A/C, and this result was
      validated in the present study using qPCR and Western blotting. Then we found
      that VEGF enhanced the invasiveness of and inhibited apoptosis in ovarian cancer
      cells as assessed by transwell invasion assays and Annexin V-FITC immunostaining,
      respectively. VEGFR was also expressed in ovarian cancer cells, as assessed by
      immunocytochemical staining. Furthermore, using the dual-luciferase report assay
      system, we demonstrated that miR-205 targeted Ezrin and Lamin A/C. MiR-205 was up
      regulated in ovarian cancer cells exposed to VEGF, as determined by miRNA
      microarray analysis and verified by qPCR. MiR-205 promoted the invasion and
      proliferation of ovarian cancer cells. CONCLUSION: Our data reveal a new
      potential pathway in which VEGF promotes the invasion of ovarian cancer cells,
      partially via the down-regulation of Ezrin and Lamin A/C caused by increased
      expression of miR-205.

PMID- 25597270
TI  - Exploring color tuning strategies in red fluorescent proteins.
AB  - Red-emitting fluorescent proteins (RFPs) with fluorescence emission above 600 nm
      are advantageous for cell and tissue imaging applications for various reasons.
      Fluorescence from an RFP is well separated from cellular autofluorescence, which
      is in the green region of the spectrum, and red light is scattered less, which
      allows thicker specimens to be imaged. Moreover, the phototoxic response of cells
      is lower for red than blue or green light exposure. Further red-shifted FP
      variants can be obtained by genetic modifications causing an extension of the
      conjugated pi-electron system of the chromophore, or by placing amino acids near
      the chromophore that stabilize its excited state or destabilize its ground state.
      We have selected the tetrameric RFP eqFP611 from Entacmaea quadricolor as a lead
      structure and discuss several rational design trials to generate RFP variants
      with improved photochemical properties. 

PMID- 25597271
TI  - Biomechanical comparison of straight DCP and helical plates for fixation of
      transverse and oblique bone fractures.
AB  - PURPOSE: Biomechanical comparison of straight DCP and helical plates for fixation
      of transversal and oblique tibial bone fractures were analyzed and compared to
      each other by axial compression, bending and torsion tests. METHOD: An in vitro
      osteosynthesis of transverse (TF) and oblique bone fracture (OF) fixations have
      been analysed on fresh sheep tibias by using the DCP and helical compression
      plates (HP). RESULTS: Statistically significant differences were found for both
      DCP and helical plate fixations under axial compression, bending and torsional
      loads. The strength of fixation systems was in favor of DC plating with exception
      of the TF-HP fixation group under compression loads and torsional moments. The
      transvers fracture (TF) stability was found to be higher than that found in
      oblique fracture (OF) fixed by helical plates (HP). However, under torsional
      testing, compared to conventional plating, the helical plate fixations provided a
      higher torsional resistance and strength. The maximum stiffness at axial
      compression loading and maximum torsional strength was achieved in torsional
      testing for the TF-HP fixations. CONCLUSION: From in vitro biomechanical
      analysis, fracture type and plate fixation system groups showed different
      responses under different loadings. Consequently, current biomechanical analyses
      may encourage the usage of helical HP fixations in near future during clinical
      practice for transverse bone fractures.

PMID- 25597272
TI  - Modulation of OCT3 expression by stress, and antidepressant-like activity of
      decynium-22 in an animal model of depression.
AB  - The organic cation transporter-3 (OCT3) is a glucocorticoid-sensitive uptake
      mechanism that has been shown to regulate the bioavailability of monoamines in
      brain regions that are implicated in the pathophysiology of depression. In the
      present study, the relative impacts of acute stress alone and acute stress with a
      history of repeated stress (chronic+acute) were evaluated in two strains of rats:
      the stress-vulnerable Wistar-Kyoto (WKY) strain and the somewhat more stress
      resilient Long-Evans (LE) strain. OCT3 mRNA was significantly upregulated in the
      hippocampus of LE rats 2h after exposure to acute restraint stress, but not in
      acutely-restrained rats with a history of repeated social defeat stress. WKY rats
      exhibited a very different pattern. OCT3 mRNA was unaffected by acute restraint
      stress alone but was robustly upregulated after repeated+acute stress. There was
      also a corresponding increase in cytosolic OCT3 protein following repeated+acute
      stress in WKY rats 3h after presentation of the acute stressor. These results are
      consistent with the hypothesis that altered expression of the OCT3 may play a
      role in stress coping, and strain differences in regulation of this expression
      may contribute to differences in physiological and behavioral responses to
      stress. Furthermore, the OCT3 inhibitor, decynium 22 (1 and 10MUg/kg, i.p.)
      reduced immobility of WKY rats, but not that of LE rats, in the forced swim test,
      suggesting that blockade of the OCT3 has antidepressant-like effects. Since WKY
      rats also appear to be resistant to the behavioral effects of traditional
      antidepressants, this also suggests that OCT3 antagonism may be an alternative
      therapeutic strategy for the treatment of depression in individuals who do not
      respond to conventional antidepressants. 

PMID- 25597273
TI  - Study on self-assessment regarding knowledge of temporomandibular disorders in
      children/adolescents by Swedish and Saudi Arabian dentists.
AB  - OBJECTIVE: To estimate the degree of self-assessed knowledge among dentists in
      Sweden and Saudi Arabia regarding temporomandibular disorders (TMD) in children
      and adolescents using a summative form of assessment and further to investigate
      the possible factors that may influence the self-assessed knowledge. MATERIALS
      AND METHODS: A questionnaire survey covering four domains (Etiology; Diagnosis
      and classification; Chronic pain and pain behavior; Treatment and prognosis)
      regarding TMD knowledge was used. Out of 250 questionnaires (125 in each country)
      a total of 65 (52%) were returned in Sweden and 104 (83%) in Saudi Arabia.
      RESULTS: Self-assessed individual knowledge was significantly associated to the
      level of actual knowledge among the Swedish groups in the domains Etiology;
      Diagnosis and classification and Treatment and prognosis (p < 0.05). However, in
      the Saudi Arabian groups a corresponding significant association was only found
      in the domain Diagnosis and classification (p < 0.05). CONCLUSIONS: This study
      showed that there is a difference in the accuracy of self-assessment of own
      knowledge between the dentists in Sweden and Saudi Arabia. The Swedish dentists
      have a better ability to assess their level of knowledge compared to Saudi
      Arabian dentists regarding TMD in children and adolescents. This difference could
      be related to several factors such as motivation, positive feedback, reflection,
      psychomotor, and interpersonal skills, which all are more dominant in the Swedish
      educational tradition.

PMID- 25597274
TI  - Bronchiolitis associated with Mycoplasma pneumoniae in infants in Suzhou China
      between 2010 and 2012.
AB  - Viruses cause most cases of bronchiolitis in infants; consequently the importance
      of other agents such as Mycoplasma pneumoniae (MP) in the etiology of
      bronchiolitis may not be fully recognized. We investigated the prevalence and
      seasonal distribution of bronchiolitis caused by MP in 674 children admitted to
      the Children's Hospital affiliated with Soochow University from January 2010 to
      December 2012. The presence of MP was confirmed by real-time PCR. During the 3
      years, we identified MP in 17.2% of the children with bronchiolitis. The annual
      MP detection rates were 16.6% in 2010, 17.8% in 2011, and 17.2% in 2012. MP was
      detected throughout the year, with a peak from July to September. The median age
      of MP-positive children was 10 months. Common clinical manifestations included
      cough, wheezing, and high fever. Moist and/or wheezing rales were frequent, and
      pulmonary interstitial infiltration was seen in 66.4% of chest X-rays. Patients
      with MP infection were older, were more likely to have pulmonary interstitial
      infiltration, and had shorter hospital stays than those with respiratory
      syncytial virus infection. Our study revealed MP as an important cause of
      bronchiolitis, with peaks of occurrence during the summer and early autumn.
      Pulmonary interstitial infiltrations were a common event. 

PMID- 25597276
TI  - Conducting processes in simulated chronic inflammatory demyelinating
      polyneuropathy at 20 degrees C-42 degrees C.
AB  - Decreased conducting processes leading usually to conduction block and increased
      weakness of limbs during cold (cold paresis) or warmth (heat paresis) have been
      reported in patients with chronic inflammatory demyelinating polyneuropathy
      (CIDP). To explore the mechanisms of these symptoms, the effects of temperature
      (from 20 degrees C to 42 degrees C) on nodal action potentials and their current
      kinetics in previously simulated case of 70% CIDP are investigated, using our
      temperature dependent multi-layered model of the myelinated human motor nerve
      fiber. The results show that potential amplitudes have a bifid form at 20 degrees
      C. As in the normal case, for the CIDP case, the nodal action potentials are
      determined mainly by the nodal sodium currents (I Na ) for the temperature range
      of 20-39 degrees C, as the contribution of nodal fast and slow potassium currents
      (I Kf and I Ks ) to the total ionic current (Ii) is negligible. Also, the
      contribution of I Kf and I Ks to the membrane repolarization is enhanced at
      temperatures higher than 39 degrees C. However, in the temperature range of 20-42
      degrees C, all potential parameters in the CIDP case, except for the conduction
      block during hyperthermia (>= 40 degrees C) which is again at 45 degrees C,
      worsen: (i) conduction velocities and potential amplitudes are decreased; (ii)
      afterpotentials and threshold stimulus currents for the potential generation are
      increased; (iii) the current kinetics of action potentials is slowed and (iv) the
      conduction block during hypothermia (<= 25 degrees C) is at temperatures lower
      than 20 degrees C. These potential parameters are more altered during
      hyperthermia and are most altered during hypothermia. The present results suggest
      that the conducting processes in patients with CIDP are in higher risk during
      hypothermia than hyperthermia. 

PMID- 25597275
TI  - Therapeutic strategy for pandrug-resistant Klebsiella pneumoniae severe
      infections: short-course treatment with colistin increases the in vivo and in
      vitro activity of double carbapenem regimen.
AB  - Infections due to carbapenemase-producing Klebsiella pneumoniae represent an
      emerging threat due to the high mortality rate and lack of valid antimicrobial
      combinations, especially when the strain is colistin-resistant. We report a case
      of bloodstream infection due to pandrug-resistant K. pneumoniae treated
      successfully with an innovative regimen comprising a combination of colistin plus
      double carbapenem, along with an in vitro analysis showing the synergistic and
      bactericidal effect.

PMID- 25597277
TI  - Visual speech gestures modulate efferent auditory system.
AB  - Visual and auditory systems interact at both cortical and subcortical levels.
      Studies suggest a highly context-specific cross-modal modulation of the auditory
      system by the visual system. The present study builds on this work by sampling
      data from 17 young healthy adults to test whether visual speech stimuli evoke
      different responses in the auditory efferent system compared to visual non-speech
      stimuli. The descending cortical influences on medial olivocochlear (MOC)
      activity were indirectly assessed by examining the effects of contralateral
      suppression of transient-evoked otoacoustic emissions (TEOAEs) at 1, 2, 3 and 4
      kHz under three conditions: (a) in the absence of any contralateral noise
      (Baseline), (b) contralateral noise + observing facial speech gestures related to
      productions of vowels /a/ and /u/ and (c) contralateral noise + observing facial
      non-speech gestures related to smiling and frowning. The results are based on 7
      individuals whose data met strict recording criteria and indicated a significant
      difference in TEOAE suppression between observing speech gestures relative to the
      non-speech gestures, but only at the 1 kHz frequency. These results suggest that
      observing a speech gesture compared to a non-speech gesture may trigger a
      difference in MOC activity, possibly to enhance peripheral neural encoding. If
      such findings can be reproduced in future research, sensory perception models and
      theories positing the downstream convergence of unisensory streams of information
      in the cortex may need to be revised. 

PMID- 25597278
TI  - Characterization of age-associated changes in peripheral organ and brain region
      weights in C57BL/6 mice.
AB  - In order to further understand age-related physiological changes and to have in
      depth reference values for C57BL/6 mice, we undertook a study to assess the
      effects of aging on peripheral organ weights, and brain region weights in wild
      type C57BL/6 male mice. Peripheral organs, body and brain region weights were
      collected from young (3-4 months), mid (12 months), old (23-28 months) and very
      old (>30 months) mice. Significant increases are observed with aging in body,
      liver, heart, kidney and spleen organ weights. A decrease in organ weight is
      observed with aging in liver and kidney only in the very old mice. In contrast,
      testes weight decreases with age. Within the brain, hippocampi, striata and
      olfactory bulbs weight decreases with age. These data further our knowledge of
      the anatomical and biological changes that occur with aging and provide reference
      values for physiological-based pharmacokinetic studies in C57BL/6 mice.

PMID- 25597279
TI  - Mechanical systems biology of C. elegans touch sensation.
AB  - The sense of touch informs us of the physical properties of our surroundings and
      is a critical aspect of communication. Before touches are perceived, mechanical
      signals are transmitted quickly and reliably from the skin's surface to mechano
      electrical transduction channels embedded within specialized sensory neurons. We
      are just beginning to understand how soft tissues participate in force
      transmission and how they are deformed. Here, we review empirical and theoretical
      studies of single molecules and molecular ensembles thought to be involved in
      mechanotransmission and apply the concepts emerging from this work to the sense
      of touch. We focus on the nematode Caenorhabditis elegans as a well-studied model
      for touch sensation in which mechanics can be studied on the molecular, cellular,
      and systems level. Finally, we conclude that force transmission is an emergent
      property of macromolecular cellular structures that mutually stabilize one
      another. 

PMID- 25597283
TI  - The swinging pendulum between consensus and controversy in veterinary emergency
      and critical care.

PMID- 25597282
TI  - Organic phototransistors using poly(3-hexylthiophene) nanofibres.
AB  - Here we report the fabrication of nanofibre-based organic phototransistors (OPTs)
      using preformed poly(3-hexylthiophene) (P3HT) nanofibres. OPT performance is
      analysed based on two important parameters: photoresponsivity R and
      photosensitivity P. Before testing the devices as OPTs, the normal organic field
      effect transistor (OFET) operation is characterized, revealing a surface-coverage
      dependent performance. With R reaching 250 A W(-1) in the on-state (V(GS) = -40
      V) and P reaching 6.8 * 10(3) in the off-state (V(GS) = 10 V) under white light
      illumination (I(inc) = 0.91 mW cm(-2)), the best nanofibre-based OPTs outperform
      the OPTs fabricated from a solution of P3HT in chlorobenzene, in which no
      preformed fibres are present. The better performance is attributed to an increase
      in active layer crystallinity, a better layer connectivity and an improved edge
      on orientation of the thiophene rings along the polymer backbone, resulting in a
      longer exciton diffusion length and enhanced charge carrier mobility, linked to a
      decreased interchain coupling energy. In addition, the increased order in the
      active layer crystallinity induces a better spectral overlap between the white
      light emission spectrum and the active layer absorption spectrum, and the
      absorption of incident light is maximised by the favourable parallel orientation
      of the polymer chains with respect to the OPT substrate. Combining both leads to
      an increase in the overall light absorption. In comparison with previously
      reported solution-processed organic OPTs, it is shown here that no special
      dielectric surface treatment or post-deposition treatment of the active device
      layer is needed to obtain high OPT performance. Finally, it is also shown that,
      inherent to an intrinsic gate-tuneable gain mechanism, changing the gate
      potential results in a variation of R over at least five orders of magnitude. As
      such, it is shown that R can be adjusted according to the incident light
      intensity.

PMID- 25597280
TI  - Genetic targeting of sprouting angiogenesis using Apln-CreER.
AB  - Under pathophysiological conditions in adults, endothelial cells (ECs) sprout
      from pre-existing blood vessels to form new ones by a process termed
      angiogenesis. During embryonic development, Apelin (APLN) is robustly expressed
      in vascular ECs. In adult mice, however, APLN expression in the vasculature is
      significantly reduced. Here we show that APLN expression is reactivated in adult
      ECs after ischaemia insults. In models of both injury ischaemia and tumor
      angiogenesis, we find that Apln-CreER genetically labels sprouting but not
      quiescent vasculature. By leveraging this specific activity, we demonstrate that
      abolishment of the VEGF-VEGFR2 signalling pathway as well as ablation of
      sprouting ECs diminished tumour vascularization and growth without compromising
      vascular homeostasis in other organs. Collectively, we show that Apln-CreER
      distinguishes sprouting vessels from stabilized vessels in multiple pathological
      settings. The Apln-CreER line described here will greatly aid future mechanistic
      studies in both vascular developmental biology and adult vascular diseases. 

PMID- 25597284
TI  - Western blotting revisited: critical perusal of underappreciated technical
      issues.
AB  - The most commonly used semiquantitative analysis of protein expression still
      employs protein separation by denaturing SDS-PAGE with subsequent Western
      blotting and quantification of the resulting ODs of bands visualized with
      specific antibodies. However, many questions regarding this procedure are usually
      ignored, although still in need of answering: Does isolation or separation
      procedure harm the integrity or affect modifications (e.g., phosphorylation) of
      the protein of interest? Does denaturation reduce binding of antibodies used for
      detection? Should denaturation be performed or should a native gel be run? How
      can artificial degradations or aggregations be distinguished from biological
      relevant ones? If the antibody detects multiple bands (which is not uncommon),
      which one(s) should be taken into account for quantification and why? Which
      loading control protein should be chosen and is it really "housekeeping" and how
      can this be verified? Is the image acquisition system linear and does it come
      with a sufficient dynamic range? How to account and control for background
      staining? This article is intended to address these questions and raise the
      readers awareness to possible Western blot alternatives in the attempt of
      minimizing possible pitfalls that might loom anywhere from protein isolation to
      acquisition of final quantitative data.

PMID- 25597285
TI  - Shoot and root branch growth angle control-the wonderfulness of lateralness.
AB  - The overall shape of plants, the space they occupy above and below ground, is
      determined principally by the number, length, and angle of their lateral
      branches. The function of these shoot and root branches is to hold leaves and
      other organs to the sun, and below ground, to provide anchorage and facilitate
      the uptake of water and nutrients. While in some respects lateral roots and
      shoots can be considered mere iterations of the primary root-shoot axis, in
      others there are fundamental differences in their biology, perhaps most
      conspicuously in the regulation their angle of growth. Here we discuss recent
      advances in the understanding of the control of branch growth angle, one of the
      most important but least understood components of the wonderful diversity of
      plant form observed throughout nature. 

PMID- 25597281
TI  - Interleukin polymorphisms associated with overall survival, disease-free
      survival, and recurrence in non-small cell lung cancer patients.
AB  - Biomarkers based on germline DNA variations could have translational implications
      by identifying prognostic factors and sub-classifying patients to tailored,
      patient-specific treatment. To investigate the association between germline
      variations in interleukin (IL) genes and lung cancer outcomes, we genotyped 251
      single nucleotide polymorphisms (SNPs) from 33 different IL genes in 651 non
      small cell lung cancer (NSCLC) patients. Analyses were performed to investigate
      overall survival, disease-free survival, and recurrence. Our analyses revealed 24
      different IL SNPs significantly associated with one or more of the lung cancer
      outcomes of interest. The GG genotype of IL16:rs7170924 was significantly
      associated with disease-free survival (HR = 0.65; 95% CI 0.50-0.83) and was the
      only SNP that produced a false discovery rate (FDR) of modest confidence that the
      association is unlikely to represent a false-positive result (FDR = 0.142).
      Classification and regression tree (CART) analyses were used to identify
      potential higher-order interactions. We restricted the CART analyses to the five
      SNPs that were significantly associated with multiple endpoints (IL1A:rs1800587,
      IL1B:rs1143634, IL8:s12506479, IL12A:rs662959, and IL13:rs1881457) and
      IL16:rs7170924 which had the lowest FDR. CART analyses did not yield a tree
      structure for overall survival; separate CART tree structures were identified for
      recurrence, based on three SNPs (IL13:rs1881457, IL1B:rs1143634, and
      IL12A:rs662959), and for disease-free survival, based on two SNPs (IL12A:rs662959
      and IL16:rs7170924), which may suggest that these candidate IL SNPs have a
      specific impact on lung cancer progression and recurrence. These data suggest
      that germline variations in IL genes are associated with clinical outcomes in
      NSCLC patients.

PMID- 25597286
TI  - Antimony-dependent expansion for the Keggin heteropolyniobate family.
AB  - Nine new Sb-bicapped alpha-Keggin-type heteropolyoxoniobates (HPNb) were
      synthesized under hydrothermal conditions. Among them, the As-centered HPNb was
      never reported before, and the two dimer compounds are the biggest isolated HPNbs
      at present. 

PMID- 25597288
TI  - A model study on the photochemical isomerization of cyclic silenes.
AB  - The mechanism for the photochemical isomerization reaction is investigated
      theoretically using a model system of a five-membered-ring silene and the
      CAS(8,8)/6-311G(d) and MP2-CAS-(8,8)/6-311++G(3df,3pd)//CAS(8,8)/6-311G(d)
      methods. These model investigations indicate that the preferred reaction route
      for a five-membered-ring silene, which leads to the photorearrangement product,
      is as follows: reactant -> Franck-Condon region -> conical intersection->
      photoproduct. In other words, the direct mechanism is a one-step process that has
      no barrier. These theoretical results agree with the available experimental
      observations. 

PMID- 25597287
TI  - A genetic risk score is associated with hepatic triglyceride content and non
      alcoholic steatohepatitis in Mexicans with morbid obesity.
AB  - BACKGROUND AND AIMS: Genome-wide association studies have identified single
      nucleotide polymorphisms (SNPs) near/in PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR
      genes associated with non-alcoholic fatty liver disease (NAFLD) mainly in
      individuals of European ancestry. The aim of the study was to test whether these
      genetic variants and a genetic risk score (GRS) are associated with elevated
      liver fat content and non-alcoholic steatohepatitis (NASH) in Mexicans with
      morbid obesity. METHODS: 130 morbidly obese Mexican individuals were genotyped
      for six SNPs in/near PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes. Hepatic fat
      content [triglyceride (HTG) and total cholesterol (HTC)] was quantified directly
      in liver biopsies and NASH was diagnosed by histology. A GRS was tested for
      association with liver fat content and NASH using logistic regression models. In
      addition, 95 ancestry-informative markers were genotyped to estimate population
      admixture proportions. RESULTS: After adjusting for age, sex and admixture,
      PNPLA3, LYPLAL1, GCKR and PPP1R3B polymorphisms were associated with higher HTG
      content (P < 0.05 for PNPLA3, LYPLAL1, GCKR polymorphisms and P = 0.086 for
      PPP1R3B). The GRS was significantly associated with higher HTG and HTC content (P
      = 1.0 * 10(-4) and 0.048, respectively), steatosis stage (P = 0.029), and higher
      ALT levels (P = 0.002). Subjects with GRS >= 6 showed a significantly increased
      risk of NASH (OR = 2.55, P = 0.045) compared to those with GRS <= 5. However, the
      GRS did not predict NASH status, as AUC of ROC curves was 0.56 (P = 0.219).
      CONCLUSION: NAFLD associated loci in Europeans and a GRS based on these loci
      contribute to the accumulation of hepatic lipids and NASH in morbidly obese
      Mexican individuals.

PMID- 25597289
TI  - A study of ER stress in rat model of cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis (CVST) is a rare form of stroke. The role of
      endoplasmic reticulum (ER) stress markers is well documented in arterial stroke
      but has not been evaluated in venous stroke. The present study has been
      undertaken to investigate the role of ER stress in rodent model of CVST. For
      inducing CVST, a cranial window was made to expose superior sagittal sinus (SSS).
      A strip of filter paper soaked with 40% ferric chloride was applied on exposed
      cranial window while in sham operated control 0.9% saline was used. Clinical
      evaluations were done on day 1, 2, and 7 for neurological deficit. Rota rod test
      and brain infarction volume were also measured. Brain tissue was collected from
      infarcted portion for further analysis using real time polymerase chain reaction
      and western blot technique for ER stress markers. Augmented expression of ER
      stress markers and up regulation of apoptotic genes were found in infarcted
      tissue. These markers improved on day 7. It is concluded that ER markers are up
      regulated at an early stage of CVST and may be important in pathophysiology. 

PMID- 25597291
TI  - Gibbon (Hylobates lar) reintroduction success in Phuket, Thailand, and its
      conservation benefits.
AB  - We summarize the results from a long-term gibbon reintroduction project in
      Phuket, Thailand, and evaluate its benefits to conservation. Between October 2002
      and November 2012, eight breeding families of white-handed gibbons (Hylobates
      lar) were returned to the wild in Khao Phra Thaew non-hunting area (KPT). Wild
      gibbons were extirpated from Phuket Island by the early 1980s, but the illegal
      wildlife trade has continued to bring young gibbons from elsewhere to the
      island's popular tourist areas as pets and photo props. The Gibbon Rehabilitation
      Project (GRP) has rescued and rehabilitated confiscated and donated captive
      gibbons since 1992 and aims to repopulate the island's last sizable forest area.
      Following unsuccessful early attempts at translocation in the 1990s, GRP has now
      developed specific methods for gibbon reintroduction that have led to the
      establishment of a small independent, reproducing population of captive-raised
      and wild-born gibbons on Phuket. Eleven infants have been born wild within the
      reintroduced population, including a second generation wild-born gibbon in
      September 2012. Benefits of the GRP project include restoration of the gibbon
      population on Phuket, rescue of illegally kept gibbons, public education,
      training of personnel in gibbon conservation work, and gaining experience which
      may prove useful in saving more severely threatened species. It is unlikely that
      gibbon (and other large primate) translocations will make a significant
      contribution to conservation of the species as a whole, and primate translocation
      projects should not be judged solely by this criterion.

PMID- 25597290
TI  - Conditioned medium of dental pulp cells stimulated by Chinese propolis show
      neuroprotection and neurite extension in vitro.
AB  - The purpose of this study was to clarify the effect of Chinese propolis on the
      expression level of neurotrophic factors in dental pulp cells (DPCs). We also
      investigated that the effects of the conditioned medium (CM) of DPCs stimulated
      by the propolis against oxidative and endoplasmic reticulum (ER) stresses in
      human neuroblastoma SH-SY5Y cells, and on neurite extensions in rat adrenal
      pheochromocytoma PC12 cells. To investigate the effect of the propolis on the
      levels of neurotrophic factors in DPCs, we performed a qRT-PCR experiment. As
      results, NGF, but not BDNF and NT-3, in DPCs was significantly elevated by the
      propolis in a concentration-dependent manner. H2O2-induced cell death was
      significantly inhibited by the treatment with the CM of DPCs. In addition, the
      treatment with the propolis-stimulated CM of DPCs had a more protective effect
      than that with the CM of DPCs. We also examine the effect of the propolis
      stimulated CM of DPCs against a tunicamycin-induced ER stress. The treatment with
      the propolis-stimulated CM as well as the CM of DPCs significantly inhibited
      tunicamycin-induced cell death. Moreover, the treatment with the propolis
      stimulated CM of DPCs significantly induced neurite outgrowth from PC12 cells
      than that with the CM of DPCs. These results suggest that the CM of DPCs as well
      as DPCs will be an efficient source of new treatments for neurodegenerative
      diseases and that the propolis promote the advantage of the CM of DPCs via
      producing neurotrophic factors. 

PMID- 25597292
TI  - Comment on "B38: an all-boron fullerene analogue" by J. Lv, Y. Wang, L. Zhu and
      Y. Ma, Nanoscale, 2014, 6, 11692.
AB  - In a recent paper (Nanoscale, 2014, 6, 11692), based on the results computed
      using DFT and MP2 methods, the all-boron fullerene I was reported to be the
      global minimum of the cluster B38 and was much more stable than the quasi-planar
      II. In this comment, we have shown that at higher level of theory CCSD(T), both
      structure I and quasi-planar II are almost degenerate in energy and the B38 can
      be considered to be of a transition size between 2D and 3D boron clusters. While
      the MP2 method favours the 3D structure I, the CCSD method tends to overestimate
      the relative stability of the 2D structure II.

PMID- 25597293
TI  - Selective Capture and Quick Detection of Targeting Cells with SERS-Coding
      Microsphere Suspension Chip.
AB  - Circulating tumor cells (CTCs) captured from blood fluid represent recurrent
      cancers and metastatic lesions to monitor the situation of cancers. We develop
      surface-enhanced Raman scattering (SERS)-coding microsphere suspension chip as a
      new strategy for fast and efficient capture, recovery, and detection of targeting
      cancer cells. Using HeLa cells as model CTCs, we first utilize folate as a
      recognition molecule to be immobilized in magnetic composite microspheres for
      capturing HeLa cells and attaining high capturing efficacy (up to 95%). After
      capturing cells, the composite microsphere, which utilizes a disulfide bond as
      crosslinker in the polymer shell and as a spacer for linking folate, can recycle
      90% cells within 20 min eluted by glutathion solution. Taking advantage of the
      SERS with fingerprint features, we characterize captured/recovered cells with the
      unique signal of report-molecule 4-aminothiophenol through introducing the SERS
      coding microsphere suspension chip to CTCs. Finally, the exploratory experiment
      of sieving cells shows that the magnetic composite microspheres can selectively
      capture the HeLa cells from samples of mixed cells, indicating that these
      magnetic composite microspheres have potential in real blood samples for
      capturing CTCs. 

PMID- 25597294
TI  - A novel chimeric peptide with antimicrobial activity.
AB  - Beta-lactamase-mediated bacterial drug resistance exacerbates the prognosis of
      infectious diseases, which are sometimes treated with co-administration of beta
      lactam type antibiotics and beta-lactamase inhibitors. Antimicrobial peptides are
      promising broad-spectrum alternatives to conventional antibiotics in this era of
      evolving bacterial resistance. Peptides based on the Ala46-Tyr51 beta-hairpin
      loop of beta-lactamase inhibitory protein (BLIP) have been previously shown to
      inhibit beta-lactamase. Here, our goal was to modify this peptide for improved
      beta-lactamase inhibition and cellular uptake. Motivated by the cell-penetrating
      pVEC sequence, which includes a hydrophobic stretch at its N-terminus, our
      approach involved the addition of LLIIL residues to the inhibitory peptide N
      terminus to facilitate uptake. Activity measurements of the peptide based on the
      45-53 loop of BLIP for enhanced inhibition verified that the peptide was a
      competitive beta-lactamase inhibitor with a K(i) value of 58 MUM. Incubation of
      beta-lactam-resistant cells with peptide decreased the number of viable cells,
      while it had no effect on beta-lactamase-free cells, indicating that this peptide
      had antimicrobial activity via beta-lactamase inhibition. To elucidate the
      molecular mechanism by which this peptide moves across the membrane, steered
      molecular dynamics simulations were carried out. We propose that addition of
      hydrophobic residues to the N-terminus of the peptide affords a promising
      strategy in the design of novel antimicrobial peptides not only against beta
      lactamase but also for other intracellular targets.

PMID- 25597295
TI  - Vertical bipolar charge plasma transistor with buried metal layer.
AB  - A self-aligned vertical Bipolar Charge Plasma Transistor (V-BCPT) with a buried
      metal layer between undoped silicon and buried oxide of the silicon-on-insulator
      substrate, is reported in this paper. Using two-dimensional device simulation,
      the electrical performance of the proposed device is evaluated in detail. Our
      simulation results demonstrate that the V-BCPT not only has very high current
      gain but also exhibits high BVCEO . f(T) product making it highly suitable for
      mixed signal high speed circuits. The proposed device structure is also suitable
      for realizing doping-less bipolar charge plasma transistor using compound
      semiconductors such as GaAs, SiC with low thermal budgets. The device is also
      immune to non-ideal current crowding effects cropping up at high current
      densities.

PMID- 25597296
TI  - Stereoselective synthesis of highly functionalized indanes and
      dibenzocycloheptadienes through complex radical cascade reactions.
AB  - Two highly stereoselective radical-mediated syntheses of densely functionalized
      indanes and dibenzocycloheptadienes from ortho-vinyl- and ortho-vinylaryl
      substituted N-(arylsulfonyl)-acrylamides, respectively, are presented here. The
      chemoselective addition of in situ generated radicals (X(.)) onto the styrene
      moieties triggers an unprecedented reaction cascade, resulting in the formation
      of one new C-X bond and two new C-C bonds, a formal 1,4-aryl migration, and the
      extrusion of SO2 to generate an amidyl radical intermediate. This intermediate,
      upon H abstraction, leads to the observed 5- and 7-membered ring carbocyclic
      products, respectively, in a highly efficient manner.

PMID- 25597297
TI  - Is electromyography a predictive test of patient response to biofeedback in the
      treatment of fecal incontinence?
AB  - AIM: Biofeedback is effective in more than 70% of patients with fecal
      incontinence. However, reliable predictors of successful treatment have not been
      identified. The aim was to identify clinical variables and diagnostic tests,
      particularly electromyography, that could predict a successful outcome. METHODS:
      We included 135 consecutive women with fecal incontinence treated with
      biofeedback. Clinical evaluation, manometry, ultrasonography, electromyography,
      and pudendal nerve terminal motor latency were performed before therapy.
      Treatment outcome was assessed using a symptoms diary, Wexner incontinence score
      and the patient's subjective perception. RESULTS: According to the symptoms
      diaries, 106 (78.5%) women had a good clinical result and 29 (21.5%) had a poor
      result. There were no differences in age, severity and type of fecal
      incontinence. Maximum resting pressure (39.3 +/- 19.1 mmHg vs. 33.7 +/- 20.2
      mmHg; P = 0.156) and maximum squeeze pressure (91.8 +/- 33.2 mmHg vs. 79.8 +/-
      31.2 mmHg; P = 0.127) were higher in patients having good clinical outcome
      although the difference was not significant. There were no differences in the
      presence of sphincter defects or abnormalities in electromyographic recordings.
      Logistic regression analysis found no independent predictive factor for good
      clinical outcome. CONCLUSIONS: Biofeedback is effective in more than 75% of
      patients with fecal incontinence. Clinical characteristics of patients and
      results of baseline tests have no predictive value of response to therapy.
      Specifically, we found no association between severity of electromyographic
      deficit and clinical response.

PMID- 25597298
TI  - Biphasic role of calcium in mouse sperm capacitation signaling pathways.
AB  - Mammalian sperm acquire fertilizing ability in the female tract in a process
      known as capacitation. At the molecular level, capacitation is associated with up
      regulation of a cAMP-dependent pathway, changes in intracellular pH,
      intracellular Ca(2+), and an increase in tyrosine phosphorylation. How these
      signaling systems interact during capacitation is not well understood. Results
      presented in this study indicate that Ca(2+) ions have a biphasic role in the
      regulation of cAMP-dependent signaling. Media without added Ca(2+) salts (nominal
      zero Ca(2+)) still contain micromolar concentrations of this ion. Sperm incubated
      in this medium did not undergo PKA activation or the increase in tyrosine
      phosphorylation suggesting that these phosphorylation pathways require Ca(2+).
      However, chelation of the extracellular Ca(2+) traces by EGTA induced both cAMP
      dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA
      effect in nominal zero Ca(2+) media was mimicked by two calmodulin antagonists,
      W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These
      results suggest that Ca(2+) ions regulate sperm cAMP and tyrosine phosphorylation
      pathways in a biphasic manner and that some of its effects are mediated by
      calmodulin. Interestingly, contrary to wild-type mouse sperm, sperm from CatSper1
      KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon
      incubation in nominal zero Ca(2+) media. Therefore, sperm lacking Catsper Ca(2+)
      channels behave as wild-type sperm incubated in the presence of EGTA. This latter
      result suggests that Catsper transports the Ca(2+) involved in the regulation of
      cAMP-dependent and tyrosine phosphorylation pathways required for sperm
      capacitation.

PMID- 25597301
TI  - Mechanisms and rates of proton transfer to coordinated carboxydithioates: studies
      on [Ni(S2CR){PhP(CH2CH2PPh2)2}](+) (R = Me, Et, Bu(n) or Ph).
AB  - The complexes [Ni(S2CR)(triphos)]BPh4 (R = Me, Et, Bu(n) or Ph; triphos =
      PhP{CH2CH2PPh2}2) have been prepared and characterised. X-ray crystallography
      (for R = Et, Ph, C6H4Me-4, C6H4OMe-4 and C6H4Cl-4) shows that the geometry of the
      five-coordinate nickel in the cation is best described as distorted trigonal
      bipyramidal, containing a bidentate carboxydithioate ligand with the two sulfur
      atoms spanning axial and equatorial sites, the other axial site being occupied by
      the central phosphorus of triphos. The reactions of [Ni(S2CR)(triphos)](+) with
      mixtures of HCl and Cl(-) in MeCN to form equilibrium solutions containing
      [Ni(SH(S)CR)(triphos)](2+) have been studied using stopped-flow
      spectrophotometry. The kinetics show that proton transfer is slower than the
      diffusion-controlled limit and involves at least two coupled equilibria. The
      first step involves the rapid association between [Ni(S2CR)(triphos)](+) and HCl
      to form the hydrogen-bonded precursor, {[Ni(S2CR)(triphos)](+)HCl} (K) and this
      is followed by the intramolecular proton transfer (k) to produce
      [Ni(SH(S)CR)(triphos)](2+). In the reaction of [Ni(S2CMe)(triphos)](+) the rate
      law is consistent with the carboxydithioate ligand undergoing chelate ring
      opening after protonation. It seems likely that chelate ring-opening occurs for
      all [Ni(S2CR)(triphos)](+), but only with [Ni(S2CMe)(triphos)](+) is the
      protonation step sufficiently fast that chelate ring-opening is rate-limiting.
      With all other systems, proton transfer is rate-limiting. DFT calculations
      indicate that protonation can occur at either sulfur atom, but only protonation
      at the equatorial sulfur results in chelate ring-opening. The ways in which
      protonation of either sulfur atom complicates the analyses and interpretation of
      the kinetics are discussed. 

PMID- 25597299
TI  - Collagen Scaffolds Incorporating Coincident Gradations of Instructive Structural
      and Biochemical Cues for Osteotendinous Junction Engineering.
AB  - A fully 3D biomaterial containing overlapping gradations of structural,
      compositional, and biomolecular cues as seen in native orthopedic interfaces is
      described for the first time. A multi-compartment collagen scaffold is created
      for engineering tendon-bone junctions connected by a continuous interface that
      can induce spatially specific MSC differentiation down tenogenic and osteogenic
      lineages without the use of differentiation media. 

PMID- 25597300
TI  - Mycorrhizal fungal communities in coastal sand dunes and heaths investigated by
      pyrosequencing analyses.
AB  - Maritime sand dunes and coastal ericaceous heaths are unstable and dynamic
      habitats for mycorrhizal fungi. Creeping willow (Salix repens) is an important
      host plant in these habitats in parts of Europe. In this study, we wanted to
      assess which mycorrhizal fungi are associated with S. repens in four different
      coastal vegetation types in Southern Norway, three types from sand dunes and one
      from heaths. Moreover, we investigated which ecological factors are important for
      the fungal community structure in these vegetation types. Mycorrhizal fungi on S.
      repens root samples were identified by 454 pyrosequencing of tag-encoded internal
      transcribed spacer 1 (ITS1) amplicons. Significantly higher fungal richness was
      observed in hummock dunes and dune slacks compared to eroded dune vegetation. The
      compositional variation was mainly accounted for by location (plot) and
      vegetation type and was significantly correlated to content of carbon, nitrogen
      and phosphorus in soil. The investigated maritime sand dunes and coastal
      ericaceous heaths hosted mycorrhizal taxa mainly associated with Helotiales,
      Sebacinales, Thelephorales and Agaricales. 

PMID- 25597302
TI  - Evaluating bone health in inflammatory bowel disease--a single tertiary care
      Veterans Hospital experience.

PMID- 25597303
TI  - Risk factors for cytomegalovirus reactivation after liver transplantation: can
      pre-transplant cytomegalovirus antibody titers predict outcome?
AB  - Despite preexisting cytomegalovirus (CMV) immunity, CMV-seropositive liver
      transplantation (LT) patients remain at risk of CMV infection. We hypothesized
      that the pre-transplant CMV antibody titer correlates with the risk of CMV
      reactivation. We conducted a retrospective study of CMV-seropositive LT
      recipients who did not receive anti-CMV prophylaxis from 2007 to 2013. The pre
      transplant CMV immunoglobulin G (IgG) titer, which was measured with an enzyme
      linked fluorescent immunoassay, was assessed as a risk factor for CMV
      reactivation with multivariate Cox proportional hazards models. The population
      consisted of 225 CMV-seropositive LT patients with a median age of 57 years
      (interquartile range, 47-62 years). The CMV titer distributions were as follows:
      <60 (40%) and >=60 AU/mL (60%). The Kaplan-Meier estimates for CMV infection were
      17% at 3 months, 18% at 6 months, and 19% at 12 months after transplantation. In
      a univariate analysis, a marginally significant increased risk of CMV infection
      was seen in LT recipients with a pre-transplant CMV IgG titer<60 AU/mL versus
      >=60 AU/mL [hazard ratio (HR), 1.79; 95% confidence interval (CI), 0.98-3.28
      (P=0.06)]. This risk was statistically significant in the subgroup of recipients
      who received allografts from CMV-seropositive donors [HR, 2.21; 95% CI, 1.15-4.26
      (P=0.02)]. In a multivariate analysis, a pre-transplant CMV IgG titer<60 AU/mL
      was significantly associated with CMV infection [HR, 3.11; 95% CI, 1.60-6.03
      (P<0.001)]. The other risk factors were high body mass index, donor CMV
      seropositivity, prolonged cold ischemic time, use of an interleukin-2 receptor
      antagonist for induction therapy, and high numbers of post-transplant infections.
      A lower pre-transplant CMV antibody titer is significantly associated with CMV
      infection after LT. Quantitative measurement of CMV-specific humoral immunity may
      have a potential role in improving the CMV prevention strategy in CMV
      seropositive LT recipients.

PMID- 25597304
TI  - A gold nanoparticle-based label free colorimetric aptasensor for adenosine
      deaminase detection and inhibition assay.
AB  - A novel strategy for the fabrication of a colorimetric aptasensor using label
      free gold nanoparticles (AuNPs) is proposed in this work, and the strategy has
      been employed for the assay of adenosine deaminase (ADA) activity. The aptasensor
      consists of adenosine (AD) aptamer, AD and AuNPs. The design of the biosensor
      takes advantage of the special optical properties of AuNPs and the interaction
      between AuNPs and single-strand DNA. In the absence of ADA, the AuNPs are
      aggregated and are blue in color under appropriate salt concentration because of
      the grid structure of an AD aptamer when binding to AD, while in the presence of
      the analyte, AuNPs remain dispersed with red color under the same concentration
      of salt owing to ADA converting AD into inosine which has no affinity with the AD
      aptamer, thus allowing quantitative investigation of ADA activity. The present
      strategy is simple, cost-effective, selective and sensitive for ADA with a
      detection limit of 1.526 U L(-1), which is about one order of magnitude lower
      than that previously reported. In addition, a very low concentration of the
      inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) could generate a
      distinguishable response. Therefore, the AuNP-based colorimetric biosensor has
      great potential in the diagnosis of ADA-relevant diseases and drug screening. 

PMID- 25597305
TI  - Antimicrobials: a new drug for resistant bugs.

PMID- 25597306
TI  - Rapid identification of oral Actinomyces species cultivated from subgingival
      biofilm by MALDI-TOF-MS.
AB  - BACKGROUND: Actinomyces are a common part of the residential flora of the human
      intestinal tract, genitourinary system and skin. Isolation and identification of
      Actinomyces by conventional methods is often difficult and time consuming. In
      recent years, matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS) has become a rapid and simple method to identify
      bacteria. OBJECTIVE: The present study evaluated a new in-house algorithm using
      MALDI-TOF-MS for rapid identification of different species of oral Actinomyces
      cultivated from subgingival biofilm. DESIGN: Eleven reference strains and 674
      clinical strains were used in this study. All the strains were preliminarily
      identified using biochemical methods and then subjected to MALDI-TOF-MS analysis
      using both similarity-based analysis and classification methods (support vector
      machine [SVM]). The genotype of the reference strains and of 232 clinical strains
      was identified by sequence analysis of the 16S ribosomal RNA (rRNA). RESULTS: The
      sequence analysis of the 16S rRNA gene of all references strains confirmed their
      previous identification. The MALDI-TOF-MS spectra obtained from the reference
      strains and the other clinical strains undoubtedly identified as Actinomyces by
      16S rRNA sequencing were used to create the mass spectra reference database.
      Already a visual inspection of the mass spectra of different species reveals both
      similarities and differences. However, the differences between them are not large
      enough to allow a reliable differentiation by similarity analysis. Therefore,
      classification methods were applied as an alternative approach for
      differentiation and identification of Actinomyces at the species level. A cross
      validation of the reference database representing 14 Actinomyces species yielded
      correct results for all species which were represented by more than two strains
      in the database. CONCLUSIONS: Our results suggest that a combination of MALDI-TOF
      MS with powerful classification algorithms, such as SVMs, provide a useful tool
      for the differentiation and identification of oral Actinomyces.

PMID- 25597307
TI  - Coordination and propulsion and non-propulsion phases in 100 meter breaststroke
      swimming.
AB  - PURPOSE: The main purpose of this study was to analyze the coordination,
      propulsion and non-propulsion phases in the 100 meter breaststroke race. METHODS:
      Twenty-seven male swimmers (15.7 +/- 1.98 years old) with the total body length
      (TBL) of 247.0 +/- 10.60 [cm] performed an all-out 100 m breaststroke bout. The
      bouts were recorded with an underwater camera installed on a portable trolley.
      The swimming kinematic parameters, stroke rate (SR) and stroke length (SL), as
      well as the coordination indices based on propulsive or non-propulsive movement
      phases of the arms and legs were distinguished. RESULTS: Swimming speed
      (V100surface breast) was associated with SL (R = 0.41, p < 0.05) and with TBL
      tending towards statistical significance (R = 0.36, p < 0.07), all relationships
      between the selected variables in the study were measured using partial
      correlations with controlled age. SL interplayed negatively with the limbs
      propulsive phase Overlap indicator (R = -0.46, p < 0.05), but had no significant
      relationship to the non-propulsion Glide indicator. CONCLUSIONS: The propulsion
      in-sweep (AP3) phase of arms and their non-propulsion partial air recovery
      (ARair) phase interplayed with V100surface breast (R = 0.51, p < 0.05 and 0.48 p
      < 0.05) respectively, displaying the importance of proper execution of this phase
      (AP3) and in reducing the resistance recovery phases in consecutive ones.

PMID- 25597308
TI  - Pine bark extracts: nutraceutical, pharmacological, and toxicological evaluation.
AB  - Proanthocyanidins are among the most abundant constituents in pine bark extracts
      (PBEs). This review summarizes medical research on PBEs from Pinus pinaster,
      Pinus radiata, Pinus massoniana, and other less well characterized species. The
      precise mechanisms of the important physiologic functions of PBE components
      remain to be elucidated, but there is evidently great potential for the
      identification and development of novel antioxidant, anti-inflammatory,
      cardiovascular, neuroprotective, and anticancer medicines. Although toxicological
      data for PBEs are limited, no serious adverse effects have been reported. PBEs,
      therefore, may have potential as nutraceuticals and pharmaceuticals and should be
      safe for use as food ingredients. 

PMID- 25597309
TI  - Inhibitory receptor-mediated regulation of natural killer cells.
AB  - Natural killer (NK) cells are capable of directly recognizing pathogens, pathogen
      infected cells, and transformed cells. NK cells recognize target cells using
      approximately 100 germ-line encoded receptors, which display activating or
      inhibitory function. NK cell activation usually requires the engagement of more
      than one receptor, and these may contribute distinct signaling inputs that are
      required for the firm adhesion of NK cells to target cells, polarization, and the
      release of cytotoxic granules, as well as the production of cytokines. In this
      article we discuss receptor-mediated mechanisms that counteract NK cell
      activation. The distinct intracellular inhibitory signaling pathways and how they
      can dominantly interfere with NK cell activation signaling events are discussed
      first. In addition, mechanisms by which inhibitory receptors modulate cellular
      activation at the level of receptor-ligand interactions are described. Receptor
      mediated inhibition of NK cell function serves three main purposes: ensuring
      tolerance of NK cells to normal cells, enabling NK cell responses to aberrant
      host cells that have lost an inhibitory ligand, and, finally, allowing the
      recognition of certain pathogens that do not express inhibitory ligands.

PMID- 25597310
TI  - Role of LAT1 in the promotion of amino acid incorporation in activated T cells.
AB  - Intake of nutrients from the environment is fundamental to cellular activity. The
      requirement of nutrients depends on the situation in which cells are placed.
      Activation of T cells changes the structure and scale of cellular metabolism,
      which requires a large amount of nutrients. Hydrophilic nutrients such as glucose
      and amino acids cannot diffuse beyond the cellular membrane; thus transporters
      are required to assist the incorporation of these nutrients into cells. Based on
      this observation, metabolic changes accompanying activation of T cells must occur
      simultaneously with the reorganization of transporters that are capable of
      providing sufficient nutrients to the cell. This review describes the functional
      advantages of using special nutrient transporters in activated T cells and
      discusses the mechanisms of responses to nutrient starvation in T cells.

PMID- 25597311
TI  - Plasma cell formation, secretion, and persistence: the short and the long of it.
AB  - B cells can be activated by cognate antigen, anti-B-cell receptor antibody,
      complement receptors, or polyclonal stimulators like lipopolysaccharide; the
      overall result is a large shift in RNA processing to the secretory-specific form
      of immunoglobulin (Ig) heavy chain mRNA and an upregulation of Igh mRNA amounts.
      Associated with this shift is the large-scale induction of Ig protein synthesis
      and the unfolded protein response to accommodate the massive quantity of
      secretory Ig that results. Stimulation to secretion also produces major
      structural accommodations and stress, with extensive generation of endoplasmic
      reticulum and Golgi as part of the cellular architecture. Reactive oxygen species
      can lead to either activation or apoptosis based on context and the high or low
      oxygen tension surrounding the cells. Transcription elongation factor ELL2 plays
      an important role in the induction of Ig secretory mRNA production, the unfolded
      protein response, and gene expression during hypoxia. After antigen stimulation,
      activated B cells from either the marginal zones or follicles can produce short
      lived antibody secreting cells; it is not clear whether cells from both locations
      can become long-lived plasma cells. Autophagy is necessary for plasma cell long
      term survival through the elimination of some of the accumulated damage to the ER
      from producing so much protein. Survival signals from the bone marrow stromal
      cells also contribute to plasma cell longevity, with BCMA serving a potentially
      unique survival role. Integrating the various information pathways converging on
      the plasma cell is crucial to the development of their long-lived, productive
      immune response.

PMID- 25597312
TI  - Role of human natural killer cells during Epstein-Barr virus infection.
AB  - Human natural killer (NK) cells have been suggested to restrict viral infections.
      However, the evidence for this notion is mostly circumstantial. Recent studies in
      mice with reconstituted human immune system components, children with symptomatic
      primary Epstein-Barr virus (EBV) infection, and in secondary lymphoid tissues of
      healthy EBV carriers have, however, shown that early differentiated human NK
      cells limit lytic EBV replication and thereby prevent the immunopathological
      expansion of lytic EBV antigen specific CD8+ T cells that is known as infectious
      mononucleosis (IM). These findings, which will be discussed in this review, might
      offer the opportunity to identify EBV negative adolescents at risk to develop IM,
      and also more generally provide a good example to document restriction of a viral
      infection by human NK cells.

PMID- 25597313
TI  - Role of p53 in systemic autoimmune diseases.
AB  - The tumor suppressor p53 has been shown to play a central role in tumor
      suppression by inducing apoptosis, cell cycle arrest, senescence, and DNA repair.
      In addition, recent observations indicate that the dysfunction of p53 is
      associated with the development of autoimmune diseases. In this review, we
      discuss the importance of p53 in various human and murine autoimmune diseases. We
      also discuss the role of p53 in controlling the balance between Th17 cells and
      Tregs, the alteration of which is shown to be involved in the development of
      autoimmunity. It is postulated that the selective restoration of p53 function in
      T cells could be applicable to the treatment of systemic autoimmune diseases.

PMID- 25597314
TI  - Dendritic cell cross talk with innate and innate-like effector cells in antitumor
      immunity: implications for DC vaccination.
AB  - Dendritic cells (DCs) are key players in the induction of immune responses.
      Adoptive transfer of autologous mature DCs loaded with tumor-associated antigens
      is a promising therapy for the treatment of immunogenic tumors. For a long time,
      its therapeutic activity was thought to depend solely on the induction of tumor
      specific CD8+ and CD4+ T cell responses. More recently, DCs were shown to
      bidirectionally interact with innate and innate-like immune cells, including
      natural killer (NK), invariant natural killer T (iNKT), and gammadelta T cells.
      These effector cells can amplify responses induced by DCs via several mechanisms,
      including induction of DC maturation and conventional T cell priming. In
      addition, NK, iNKT, and gammadelta T cells possess cytolytic activity and can act
      directly on tumor cells. Therapeutic strategies targeting these innate and innate
      like immune cells hence hold potential to improve current DC vaccination
      protocols.

PMID- 25597315
TI  - Trichinella spiralis newborn larvae: characterization of a stage specific serine
      proteinase expression, NBL1, using monoclonal antibodies.
AB  - Trichinella spiralis is an intracellular parasitic nematode of mammalian skeletal
      muscle, causing a serious zoonotic disease in humans and showing a high economic
      impact mainly in pig breeding. Serine proteinases of T. spiralis play important
      roles in the host-parasite interactions mediating host invasion. In this study,
      we have focused on newborn larvae (NBL-1), the first identified serine proteinase
      from the NBL stage of T. spiralis. Five monoclonal antibodies (mAbs) directed
      against the C-terminal part of NBL1, were produced. These mAbs were IgG1kappa
      isotype and specifically recognized as a common motif of 10 amino acids
      (PSSGSRPTYP). Selected mAbs were further characterized using antigens from
      various developmental stages of T. spiralis. Western blot revealed that selected
      mAbs reacted with the native NBL1 at Mr 50 kDa in the adult and NBL mixed
      antigens and NBL stage alone. Indirect immunofluorescence analysis revealed that
      selected mAbs intensely stained only the embryos within the gravid females and
      the NBL. Thus, the produced mAbs are useful tools for the characterization of
      NBL1 as a major antigen of Trichinella involved in the invasion of the host but
      also for the development of new serological tests with an early detection of T.
      spiralis infection. 

PMID- 25597316
TI  - [Craniomandibular disorder/dysfunction. Characteristics and disorders of the
      masticatory organ].
AB  - The practising physician often meets patients with pain located in different
      parts of the face and facial skull, mouth opening restriction or other motion
      disorder of the mandible. It is not always easy to identify and explain the
      cause. It is not widely known among doctors that most of these problems are due
      to masticatory dysfunction. There is a special group of patients showing
      functional disorders and there are some others who present a variety of different
      symptoms and visit several doctors. The masticatory organ, a functional unit of
      the human organism has a definite and separate task and function. In the early
      years of life it is capable of adaptation, while later on it tends to
      compensation. The authors outline the functional anatomy of the masticatory organ
      and the characteristics of multicausal pathology, the dynamics of the process of
      the disease and their interdisciplinary aspects. They discuss the basic elements
      of craniomandibular dysfunction. Based on the diagnostic algorithm, they
      summarize treatment options for masticatory function disorders. They emphasize
      the importance that physicians should offer treatment, especially an irreversible
      treatment, without a diagnosis. It occurs very often that the causes are
      identified after the patients become symptom-free due to treatment. The aim of
      this report is to help the general practitioners, dentists, neurologists, ear
      nose-throat specialists, rheumatologists or any other specialists in the everyday
      practice who have patients with different symptoms such as pain in the skull,
      acoustic phenomenon of the joint or craniomandibular dysfunction.

PMID- 25597317
TI  - [Psychotherapy and efficacy].
AB  - Evaluation of the efficacy in psychotherapy dates back to the beginnings of
      psychotherapy itself. However, it is not an easy task to undertake efficacy
      evaluation because it is expensive and several methodological difficulties may be
      also present. The authors discuss some questions related efficacy evaluation in
      psychotherapy, including criteria for selecting the cases and the actual target
      of evaluation. In addition, the authors analyze the narrative psychological
      content analysis method which includes the analysis of psychological features and
      their changes of texts written by the patient about him- or herself. They
      conclude that this method can open novel perspectives in psychotherapy.

PMID- 25597318
TI  - [Low persistence of simvastatin and ezetimibe fixed combination in the lipid
      lowering therapy].
AB  - INTRODUCTION: The high cholesterol level is a well-known modifiable
      cardiovascular risk factor. Adequate patient adherence is important to decrease
      the cardiovascular risk. AIM: The aim of the authors was to evaluate the
      persistence on one-year treatment with the free or fixed combination of
      simvastatin and ezetimibe and rosuvastatin. METHOD: Information from the National
      Health Insurance Found prescriptions database on pharmacy-claims between October
      1, 2012 and September 30, 2013 was analyzed. The authors identified patients who
      filled prescriptions for fixed or free combinations of simvastatin and ezetimibe
      and rosuvastatin prescribed for the first time. The subjects have not received
      antilipemic therapy with similar drugs during the year preceding the study. Using
      Kaplan-Meier technique, the authors constructed persistence curves with a 95%
      confidence interval for point estimates calculated on a log scale. Patients who
      were still persistent at the closing date of the study were considered censored.
      For the modelling of the curves, the authors used semi-parametric Cox's
      regression where antihypertensive therapy was the only (categorical) explanatory
      variable, and the patients taking the fixed combination of simvastatin and
      ezetimibe were regarded as the reference group. RESULTS: 204,699 patients met the
      inclusion criteria. During the study period, antilipemic therapy with simvastatin
      and ezetimibe free combination 10,030 and 7,613 fixed combination of these agents
      and 187,056 patients with rosuvastatin was started by patients. One-year
      persistence rate in patients taking simvastatin and ezetimibe as a free
      combination was 10.97%, whereas it was 24.35% in those on the fixed combination
      and 30.47% in those on rosuvastatin monotherapy. The hazard ratio of
      discontinuation of simvastatin and ezetimibe free combination was 1.73 [95%
      confidence interval: 1.61-1.85], p<0.0001 compared to fixed combination and 0.80
      [95% confidence interval: 0.78-0.82], p<0.0001 compared to rosuvastatin.
      Considering only the 360-day study period, the mean duration of persistence was
      107 days in patients on the free, 164 days in those taking the free combination
      of simvastatin and ezetimibe and 185 days those taking rosuvastatin. CONCLUSIONS:
      This study demonstrated that one-year persistence of free and fixed combination
      of simvastatin and ezetimibe was significantly lower compared to rosuvastatin.

PMID- 25597319
TI  - [Assessment of risk factors for fractures in postmenopausal women with
      osteoporosis].
AB  - INTRODUCTION: The main consequence of osteoporosis is bone fracture. Bone
      fracture risk is determined by several risk factors beyond osteodensitometric
      results. Some of these factors could be estimated by simple clinical
      questionnaires. AIM: The aim of the present study (Score-HU) was to investigate
      the risk factors of bone fracture among osteoporotic postmenopausal women (n =
      11,221), who were examined in an osteologic outpatient departments. METHOD: Risk
      factors of each patient were recorded with the use of a simple identical data
      sheet. RESULTS: The incidence of risk factors were the following: previous bone
      fracture (79.4%), medication (except antiporotic treatment, antihypertensive
      drugs 67.9%, sleeping pills 36%, antidepressants 26.5%, corticosteroids 13.5%),
      decreased mobility (44.6%), early menopause (31.9%), smoking (31.2%), frequent
      falls (29.1%), and poor health status (more than 3 chronic diseases; 24.1%).
      CONCLUSIONS: Estimating the above mentioned risk factors we could assess the bone
      fracture risk more accurately than taking alone the bone mineral density results
      into consideration.

PMID- 25597320
TI  - [Migration of an epicardial pacemaker into the abdominal cavity].
AB  - Migration of a permanent pacemaker generator from their intramuscular pocket to
      the abdominal cavity is a less frequent, but potentially life-threatening
      complication. The authors present the case of a 69-year-old woman, who visited
      the emergency department of the clinic, with complains of non-specific abdominal
      symptoms. Her past medical history included a complete atrioventricular block
      diagnosed in 2009 during the mitral valve replacement and since then she had an
      epicardial permanent pacemaker; the pulse generator was placed into an
      intramuscular pouch created in the left subcostal region. Surprisingly,
      radiologic examinations showed that the generator migrated into the pouch of
      Douglas. Considering patient safety, first a new intracardiac pacemaker was
      implanted and then the migrated device was removed surgically. The patient was
      discharged on the seventh postoperative day.

PMID- 25597321
TI  - [Semmelweis and Jenner -- professor of obstetrics as the head of the Immunization
      Institute in Budapest].

PMID- 25597322
TI  - The foot deformity versus postural control in females aged over 65 years.
AB  - PURPOSE: Correct foot structure is important due to locomotion and postural
      stability. The aim of this study was to determine the relationships between
      morphological foot structure and balance indices in a quiet standing position in
      women over 65 years of age. METHODS: The study included 116 women aged 65-90
      years. The mean age was 70.6 +/- 8.4 years and BMI 29.1 +/- 3.4 m/kg2. The
      measured indices included postural control while standing on both feet and
      photogrammetric foot evaluation. An analysis was performed of the selected foot
      and balance indices. RESULTS: There were no significant differences observed in
      the feet structure. Certain correlations between some foot indices and the
      indices of postural control were noted. The increased differences in the width
      indices between the right and the left foot lead to balance deterioration. Larger
      angles of valgity and varus deformity of toes and indices describing the
      longitudinal arch and transverse front arch of the foot have the greatest impact
      on the deterioration of balance in the medio-lateral axis. CONCLUSIONS: The
      differences between the indices and morphological indices for the right and the
      left foot are not significant, which indicates the proportionate formation of
      feet in the individual life. The increased differences in the width indices
      between the right and the left foot lead to balance deterioration. Larger angles
      of valgity and varus deformity of toes and indices describing the longitudinal
      arch and transverse front arch of the foot have the greatest impact on the
      deterioration of balance in the medio-lateral axis.

PMID- 25597323
TI  - Optimum design of amphiphilic polymers bearing hydrophobic groups for both cell
      surface ligand presentation and intercellular cross-linking.
AB  - Amphiphilic polymers bearing hydrophobic alkyl groups are expected to be
      applicable for both ligand presentation on the cell surface and intercellular
      crosslinking. To explore the optimum design for each application, we synthesized
      eight different acyl-modified dextrans with varying molecular weight, alkyl
      length, and alkyl modification degree. We found that the behenate-modified
      polymers retained on the cell surface longer than the palmitate-modified ones.
      Since the polymers were also modified with biotin, streptavidin can be presented
      on the cell surface through biotin-streptavidin recognition. The duration of
      streptavidin on the cell surface is longer in the behenate-modified polymer than
      the palmitate-modified one. As for the intercellular crosslinking, the palmitate
      modified polymers were more efficient than the behenate-modified polymers. The
      findings in this research will be helpful to design the acyl-modified polymers
      for the cell surface engineering. 

PMID- 25597324
TI  - Everyday politics, social practices and movement networks: daily life in
      Barcelona's social centres.
AB  - The relations between everyday life and political participation are of interest
      for much contemporary social science. Yet studies of social movement protest
      still pay disproportionate attention to moments of mobilization, and to movements
      with clear organizational boundaries, tactics and goals. Exceptions have explored
      collective identity, 'free spaces' and prefigurative politics, but such processes
      are framed as important only in accounting for movements in abeyance, or in
      explaining movement persistence. This article focuses on the social practices
      taking place in and around social movement spaces, showing that political
      meanings, knowledge and alternative forms of social organization are continually
      being developed and cultivated. Social centres in Barcelona, Spain, autonomous
      political spaces hosting cultural and educational events, protest campaigns and
      alternative living arrangements, are used as empirical case studies. Daily
      practices of food provisioning, distributing space and dividing labour are
      politicized and politicizing as they unfold and develop over time and through
      diverse networks around social centres. Following Melucci, such latent processes
      set the conditions for social movements and mobilization to occur. However, they
      not only underpin mobilization, but are themselves politically expressive and
      prefigurative, with multiple layers of latency and visibility identifiable in
      performances of practices. The variety of political forms - adversarial,
      expressive, theoretical, and routinized everyday practices, allow diverse
      identities, materialities and meanings to overlap in movement spaces, and help
      explain networks of mutual support between loosely knit networks of activists and
      non-activists. An approach which focuses on practices and networks rather than
      mobilization and collective actors, it is argued, helps show how everyday life
      and political protest are mutually constitutive. 

PMID- 25597325
TI  - Clinical use and efficacy of biphasic insulin lispro 50/50 in people with insulin
      treated diabetes - a nationwide evaluation of clinical practice.
AB  - OBJECTIVES: This study aims to investigate the metabolic effects of biphasic
      insulin lispro 50/50 in routine clinical practice. A total of 229 patients who
      were >=18 years old with diabetes, newly treated with biphasic insulin lispro
      50/50, were sourced from six secondary care services in England. METHODS:
      Detailed clinical parameters were compared at baseline, and 3 and 6 months post
      initiation. Responders was defined as those with HbA1c <7.5% (58 mmol/mol) and/or
      an HbA1c reduction of >1% (11 mmol/mol) at 6 months. RESULTS: HbA1c showed
      significant reduction: -0.93% (-10 mmol/mol) and -1.2% (-13 mmol/mol) at 3 and 6
      months respectively, while no significant change was noted for all the other
      parameters. When analyzed according to frequencies of injections/day, the
      greatest reduction was observed with the three times a day regimen (-1.0% [-11.0
      mmol/mol] and -1.3% [-14.6 mmol/mol] at 3 and 6 months respectively). HbA1c
      reduction was greatest in the group who previously received a basal-bolus insulin
      regimen: (-0.8% [-9.0 mmol/mol] and -1.5% [-16.2 mmol/mol] at 3 and 6 months
      respectively). Reduction in weight was observed at 3 months (-1.8 kg +/- 4.3)
      only for those who were previously on a basal-bolus insulin regimen. Insulin
      doses increased following conversion to biphasic insulin lispro 50/50,
      irrespective of the types of insulin used prior to biphasic insulin lispro 50/50,
      but this was not associated with weight gain. The independent predictors of
      response to biphasic insulin lispro 50/50 were baseline HbA1c, Caucasian,
      presence of nephropathy, prior use of basal-bolus insulin and prior use of other
      premixed combination. CONCLUSION: Biphasic insulin lispro 50/50 is therefore an
      effective therapeutic option for achieving glycemic control in patients with
      suboptimal HbA1c levels, especially among those who were previously on a basal
      bolus insulin regimen and those who received it three times daily, with a neutral
      effect on weight parameters. LIMITATIONS: This was a retrospective study of
      routine clinical practice and is therefore limited by allocation bias and some
      missing data. Information on rates of hypoglycemia and quality of life are not
      available.

PMID- 25597326
TI  - In situ spectroscopic identification of neptunium(V) inner-sphere complexes on
      the hematite-water interface.
AB  - Hematite plays a decisive role in regulating the mobility of contaminants in
      rocks and soils. The Np(V) reactions at the hematite-water interface were
      comprehensively investigated by a combined approach of in situ vibrational
      spectroscopy, X-ray absorption spectroscopy and surface complexation modeling. A
      variety of sorption parameters such as Np(V) concentration, pH, ionic strength,
      and the presence of bicarbonate was considered. Time-resolved IR spectroscopic
      sorption experiments at the iron oxide-water interface evidenced the formation of
      a single monomer Np(V) inner-sphere sorption complex. EXAFS provided
      complementary information on bidentate edge-sharing coordination. In the presence
      of atmospherically derived bicarbonate the formation of the bis-carbonato inner
      sphere complex was confirmed supporting previous EXAFS findings.1 The obtained
      molecular structure allows more reliable surface complexation modeling of recent
      and future macroscopic data. Such confident modeling is mandatory for evaluating
      water contamination and for predicting the fate and migration of radioactive
      contaminants in the subsurface environment as it might occur in the vicinity of a
      radioactive waste repository or a reprocessing plant. 

PMID- 25597327
TI  - Thyroid nodules diagnosed as follicular neoplasm: do not forget Doppler US and
      correlation to previous imaging findings.

PMID- 25597328
TI  - Screening, identification and characterization of bacteriocins produced by wine
      isolated LAB strains.
AB  - AIMS: To screen and identify wine-isolated LAB strains for bacteriocin
      production, and to identify and characterize bacteriocins. METHODS AND RESULTS:
      One hundred and fifty-five LAB strains isolated from South African red wines
      undergoing spontaneous malolactic fermentation were screened for bacteriocin
      production. Eight isolates were identified to be bacteriocin producers and were
      identified as Enterococcus faecium. All eight isolates had the same phenotypic
      and genotypic profiles. The peptides were preliminarily identified as enterocin P
      using mass spectrometry and further confirmed by PCR-amplifying enterocin P gene.
      The enterocin activity was inhibited by alpha-Chymotrypsin, papain and proteinase
      K treatments. It was heat stable at 37, 60, 80 and 100 degrees C and showed
      activity over a broad pH range of 2-10. The production of the enterocin followed
      that of primary metabolite kinetics and, it showed bactericidal effect to some
      wine spoilage LAB strains. CONCLUSIONS: Our study identified the presence of the
      enterocin-producing Enterococcus in wine. The enterocin was heat stable; with
      broad pH range and bactericidal effects to sensitive strains. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This is one of very few studies that isolated Enterococcus
      species from wine. It is, however, the first to report presence of bacteriocin
      producing Enterococcus in wine fermentation.

PMID- 25597329
TI  - Feasibility of quantitative parameters of dynamically enhanced patterns of spiral
      computed tomography scanning integrated into tumour progression before targeted
      treatment of non-small cell lung cancer.
AB  - INTRODUCTION: The relationship between quantitative parameters of contrast
      enhanced computed tomography (CT) and non-small cell lung cancer (NSCLC)
      progression remains controversial. We aimed to explore the usefulness of contrast
      enhanced spiral CT scanning for confirming the time of tumour progression before
      targeted treatment of NSCLC. METHODS: Contrast-enhanced spiral CT scanning was
      performed on 33 NSCLC patients with a biopsy-proven diagnosis of NSCLC. All the
      patients were divided into three groups according to times of tumour progression
      (<6 weeks, 6-20 weeks, and >20 weeks). The perfusion CT data were used to
      calculate quantitative parameters, including enhanced peak values, peak time of
      tumour enhancement, ratio of tumour mass and enhanced aorta peak value and
      perfusion value of blood flow. Variance analysis was used for statistical
      analysis among the three groups using SAS 9.13 statistical software. RESULTS:
      Tumour perfusion values among the three group with different stage of TTP were
      significantly different from each other with P = 0.0129 (<6 weeks, perfusion
      value = 0.35 +/- 0.15 mL/(min * mL); 6-20 weeks, perfusion value = 0.41 +/- 0.086
      mL/(min * mL); > 20 weeks, perfusion value = 0.47 +/- 0.087 mL/(min * mL)).
      However, no significant differences were found in other parameters (enhanced peak
      values, peak time of tumour enhancement, ratios of tumour mass, and enhanced
      aorta peak value) among three groups (P > 0.05). CONCLUSION: The NSCLC patients
      with high perfusion value before targeted therapy are more sensitive to targeted
      therapy, and further experiments with larger sample size are needed.

PMID- 25597331
TI  - First-line gefitinib for elderly patients with advanced NSCLC harboring EGFR
      mutations. A combined analysis of North-East Japan Study Group studies.
AB  - OBJECTIVE: To assess outcomes of elderly patients with advanced NSCLC harboring
      an EGFR mutation treated with gefitinib, as well as safety and impact on quality
      of life (QoL). METHODS: We performed a retrospective analysis of pooled data from
      one Phase III and two Phase II studies of 71 patients aged >= 70 years with a
      performance status of 0 - 2. The main outcome measures were progression-free
      survival (PFS), overall survival (OS) and response rate (RR), as well as
      incidence of adverse events and time to 9.1% deterioration in QoL. RESULTS:
      Median PFS (14.3 vs 5.7 months, p < 0.001) and overall RR (73.2 vs 26.5%, p <
      0.001) in the gefitinib group were superior to those in the standard chemotherapy
      group, whereas median OS was not significantly different (30.8 vs 26.4 months, p
      = 0.42). Elevation of aspartate transaminase and/or alanine transaminase (18.3%)
      was the most common adverse event, and one treatment-related death (pneumonitis)
      occurred. Time to 9.1% deterioration in the QoL domains of pain and dyspnea,
      anxiety, and daily functioning was similar between the two age groups.
      CONCLUSION: First-line gefitinib is efficacious with acceptable toxicity in
      relatively fit elderly patients with advanced NSCLC harboring an EGFR mutation.

PMID- 25597332
TI  - Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines
      differ so much?
AB  - BACKGROUND: The use of postoperative adjuvant chemotherapy is controversial for
      rectal adenocarcinoma. Both international and national guidelines display a great
      span varying from recommending no adjuvant chemotherapy at all, over single drug
      5-fluororuacil (5-FU), to combinations of 5-FU/oxaliplatin. METHODS: A review of
      the literature was made identifying 24 randomized controlled trials on adjuvant
      treatment of rectal cancer based on about 10 000 patients. The trials were
      subdivided into a number of clinically relevant subgroups. RESULTS: As regards
      patients treated with preoperative (chemo) radiotherapy, four randomized studies
      were found where use of adjuvant chemotherapy showed no benefit in survival.
      Three trials were found in which a subset of patients received preoperative
      (chemo) radiotherapy. Two of these trials showed a statistically significant
      benefit of adjuvant chemotherapy. Twenty trials were identified in which the
      patients did not receive preoperative (chemo) radiotherapy, including five Asian
      studies in which a statistically significant benefit from adjuvant chemotherapy
      was reported. CONCLUSIONS: Most of the data found did not support the use of
      postoperative adjuvant chemotherapy for patients already treated with
      preoperative (chemo) radiotherapy. For patients not treated preoperatively,
      several studies support the use of single agent 5-FU chemotherapy. Treatment
      guidelines seem to differ according to if preoperative chemoradiation is
      considered of importance for use of adjuvant chemotherapy and if adjuvant colon
      cancer studies are considered transferrable to rectal cancer patients regardless
      of the molecular differences.

PMID- 25597330
TI  - The Danish Fetal Medicine Database: establishment, organization and quality
      assessment of the first trimester screening program for trisomy 21 in Denmark
      2008-2012.
AB  - OBJECTIVE: To describe the establishment and organization of the Danish Fetal
      Medicine Database and to report national results of first-trimester combined
      screening for trisomy 21 in the 5-year period 2008-2012. DESIGN: National
      register study using prospectively collected first-trimester screening data from
      the Danish Fetal Medicine Database. POPULATION: Pregnant women in Denmark
      undergoing first-trimester screening for trisomy 21. METHODS: Data on maternal
      characteristics, biochemical and ultrasonic markers are continuously sent
      electronically from local fetal medicine databases (Astraia Gmbh software) to a
      central national database. Data are linked to outcome data from the National
      Birth Register, the National Patient Register and the National Cytogenetic
      Register via the mother's unique personal registration number. First-trimester
      screening data from 2008 to 2012 were retrieved. MAIN OUTCOME MEASURES: Screening
      performance was assessed for the years 2008-2012 by calculating detection rates
      and screen-positive rates. RESULTS: A total of 268 342 first-trimester risk
      assessments for trisomy 21 were performed in singleton pregnancies. Participation
      rate in first-trimester screening was >90%. The national screen-positive rate
      increased from 3.6% in 2008 to 4.7% in 2012. The national detection rate of
      trisomy 21 was reported to be between 82 and 90% in the 5-year period.
      CONCLUSION: A national fetal medicine database has been successfully established
      in Denmark. Results from the database have shown that at a national level first
      trimester screening performance for trisomy 21 is high with a low screen-positive
      rate and a high detection rate.

PMID- 25597333
TI  - Intratumoral dendritic cells in the anti-tumor immune response.

PMID- 25597334
TI  - Discovery of novel 2,5-dioxoimidazolidine-based P2X(7) receptor antagonists as
      constrained analogues of KN62.
AB  - Novel 2,5-dioxoimidazolidine-based conformationally constrained analogues of KN62
      (1) were developed as P2X7 receptor (P2X7R) antagonists using a rigidification
      strategy of the tyrosine backbone of 1. SAR analysis of the 2,5
      dioxoimidazolidine scaffold indicated that piperidine substitution at the N3
      position and no substitution at N1 position were preferable. Further optimization
      of the substituents at the piperidine nitrogen and the spacer around the skeleton
      resulted in several superior antagonists to 1, including 1-adamantanecarbonyl
      analogue 21i (IC50 = 23 nM in ethidium uptake assay; IC50 = 14 nM in IL-1beta
      ELISA assay) and (3-CF3-4-Cl)benzoyl analogue (-)-21w (54 nM in ethidium uptake
      assay; 9 nM in IL-1beta ELISA assay), which was more potent than the
      corresponding (+) isomer. Compound 21w displayed potent inhibitory activity in an
      ex vivo model of LTP-induced pain signaling in the spinal cord and significant
      anti-inflammatory activity in in vivo models of carrageenan-induced paw edema and
      type II collagen-induced joint arthritis. 

PMID- 25597335
TI  - Factors associated with deterioration of self-rated chewing ability among adults
      aged 60 years and older over a 6-year period.
AB  - AIM: To assess factors associated with the deterioration of self-rated chewing
      ability among adults aged 60 years and older over a 6-year period. METHODS: We
      carried out a case-control study nested in a cohort involving 890 individuals
      living in the city of Sao Paulo from 2000 to 2006. The outcome was the reduction
      of self-rated chewing ability. Covariates on demographic, socioeconomic,
      behavior, cognitive, and functional and physical status variables were
      investigated. Simple and multiple analyses were carried out using unconditional
      logistic regression with hierarchical selection of variables. RESULTS: We
      analyzed 236 cases and 654 controls. In the unadjusted assessment, the reduction
      of self-rated chewing ability was associated with being aged older than 74 years,
      widowed, low schooling/income, not having a microwave oven or a car, physical
      inactivity, poor/regular self-rated health, to feel disgusted, poor/regular self
      rated memory, one or more compromised daily life activities, dependence for daily
      life activities and to report less than half of teeth. Older adults aged older
      than 74 years and widowers had twice the odds of the outcome in the final model.
      Adjusted for demographic variables, individuals with lower income showed a
      similar increase of odds (OR 2.06 95% CI 1.31-3.23). To report poor/regular
      memory (OR 1.85 95% CI 1.28-2.67) and less than half remaining teeth (OR 1.76
      95%CI 1.06-2.93) were significant factors in the adjusted model. CONCLUSION:
      Advanced age, low income, widowhood, poor/regular memory and less than half
      remaining teeth were important risk indicators for the reduction of self-rated
      chewing ability among individuals aged 60 years or older.

PMID- 25597337
TI  - Descriptive analysis of longitudinal endoscopy for exercise-induced pulmonary
      haemorrhage in Thoroughbred racehorses training and racing at the Hong Kong
      Jockey Club - letter.

PMID- 25597338
TI  - Skin and wound decontamination of multidrug-resistant bacteria by cold
      atmospheric plasma coagulation.
AB  - BACKGROUND AND OBJECTIVES: Novel concepts to limit the spread of multidrug
      resistant bacteria (MDR) are urgently needed. Since treatment with cold
      atmospheric plasma (CAP) has shown significant antibacterial properties, the
      purpose of this study was to evaluate the ability of CAP to eliminate MDR-
      compared to non-MDR-pathogens in chronic wounds. METHODS: Eleven patients with 18
      heavily colonized wounds were treated with a CE-certified commercial argon-based
      CAP source for 10 s/cm(2) in one session. The antimicrobial efficacy was assessed
      by calculating the microbial load before and after treatment. RESULTS: A single
      CAP treatment reduced MDR in all wounds. In 14 treatments (63.6 %) and for 16
      pathogens (66.7 %), a 100 % reduction of the bacterial load was observed. For 11
      of 17 (64.7 %) MDR-pathogens and for 5 of 7 (71.4 %) other non-MDR-pathogens,
      complete eradication was achieved. The remaining 8 treatments showed reductions
      of 77.5 +/- 18.6 % and the remaining pathogens a reduction of 74.8 +/- 25.7 %.
      CONCLUSIONS: As proof of principle, argon-based CAP serves as a potent treatment
      modality that was shown to limit MDR microbial colonization. The possible role of
      CAP in clinical MDR decontamination must be evaluated in clinical trials with
      repeated plasma treatment embedded in a comprehensive hygienic decontamination
      concept.

PMID- 25597336
TI  - Bone and the regulation of global energy balance.
AB  - The skeleton, populated by large numbers of osteoblasts and long-lived
      osteocytes, requires a constant supply of energy-rich molecules to fuel the
      synthesis, deposition and mineralization of bone matrix during bone modelling and
      remodelling. When these energetic demands are not met, bone acquisition is
      suppressed. Recent findings suggest that key developmental signals emanating from
      Wnt low-density lipoprotein-related receptor 5 and hypoxia-inducible factor
      pathways impact osteoblast bioenergetics to accommodate the energy requirements
      for bone cells to fulfil their function. In vivo studies in several mutant mouse
      strains have confirmed a link between bone cells and global metabolism,
      ultimately leading to the identification of hormonal interactions between the
      skeleton and other tissues. The hormones insulin and leptin affect postnatal bone
      acquisition, whilst osteocalcin produced by the osteoblast in turn stimulates
      insulin secretion by the pancreas. These observations have prompted additional
      questions regarding the nature of the mechanisms of fuel sensing and processing
      in the osteoblast and their contribution to overall energy utilization and
      homeostasis. Answers to such questions should advance our understanding of
      metabolic diseases and may ultimately improve management of affected patients. In
      this review, we highlight recent studies in this field and offer a perspective on
      the evolutionary implications of bone as a metabolic endocrine organ. 

PMID- 25597339
TI  - A global perspective on the epidemiology of acne.
AB  - Acne is estimated to affect 9.4% of the global population, making it the eighth
      most prevalent disease worldwide. Epidemiological studies have demonstrated that
      acne is most common in postpubescent teens, with boys most frequently affected,
      particularly with more severe forms of the disease. This paper aims to provide an
      update on the epidemiology of acne worldwide. Recent general and institutional
      studies from around the world have shown that the prevalence of acne is broadly
      consistent globally (with the exception of specific populations, which are
      discussed). However, this review highlights that there is a wide range of
      disparate outcome measures being applied in epidemiology studies, and we
      emphasize the need to develop a widely accepted, credible, standard assessment
      scale to address this in the future. In addition we discuss special populations,
      such as those devoid of acne, as well as the impact of potential determinants of
      acne on disease epidemiology.

PMID- 25597340
TI  - Diabetes mellitus in amyotrophic lateral sclerosis: Dr. Jekyll or Mr. Hyde?

PMID- 25597341
TI  - Evaluation of maillard reaction variables and their effect on heterocyclic amine
      formation in chemical model systems.
AB  - Heterocyclic amines (HCAs), highly mutagenic and potentially carcinogenic by
      products, form during Maillard browning reactions, specifically in muscle-rich
      foods. Chemical model systems allow examination of in vitro formation of HCAs
      while eliminating complex matrices of meat. Limited research has evaluated the
      effects of Maillard reaction parameters on HCA formation. Therefore, 4 essential
      Maillard variables (precursors molar concentrations, water amount, sugar type,
      and sugar amounts) were evaluated to optimize a model system for the study of 4
      HCAs: 2-amino-3-methylimidazo-[4,5-f]quinoline, 2-amino-3-methylimidazo[4,5
      f]quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-3,4,8
      trimethyl-imidazo[4,5-f]quinoxaline. Model systems were dissolved in diethylene
      glycol, heated at 175  degrees C for 40 min, and separated using reversed-phase
      liquid chromatography. To define the model system, precursor amounts (threonine
      and creatinine) were adjusted in molar increments (0.2/0.2, 0.4/0.4, 0.6/0.6, and
      0.8/0.8 mmol) and water amounts by percentage (0%, 5%, 10%, and 15%). Sugars
      (lactose, glucose, galactose, and fructose) were evaluated in several molar
      amounts proportional to threonine and creatinine (quarter, half, equi, and
      double). The precursor levels and amounts of sugar were significantly different
      (P < 0.05) in regards to total HCA formation, with 0.6/0.6/1.2 mmol producing
      higher levels. Water concentration and sugar type also had a significant effect
      (P < 0.05), with 5% water and lactose producing higher total HCA amounts. A model
      system containing threonine (0.6 mmol), creatinine (0.6 mmol), and glucose (1.2
      mmol), with 15% water was determined to be the optimal model system with glucose
      and 15% water being a better representation of meat systems. 

PMID- 25597342
TI  - Should we abandon landmark-based technique for caudal anesthesia in neonates and
      infants?
AB  - BACKGROUND: Caudal anesthesia is a landmark-based technique with ultrasound
      guidance occasionally used in the absence of landmarks. The current surface
      landmark remains a popular approach due to its desirable success rate. However,
      incomplete ossification of the posterior vertebral elements can make this
      procedure for neonatal caudal anesthesia difficult. The aim of this study was to
      describe the anatomical relationship of the posterior superior iliac spines
      (PSISs) to the sacral cornua in infants using ultrasound. METHODS: A total of 26
      healthy infants (17 female; mean age 13 weeks) were scanned by an experienced
      radiologist in the prone position with hip and knee joints flexed. The PSISs and
      sacral cornua were identified clinically then using ultrasound to assess whether
      these markings corresponded with the clinical markings. The distance between the
      PSISs and the distance between the tip of the PSIS and tip of the sacral cornu
      were measured using ultrasound. RESULTS: The PSISs were clinically identified in
      all babies, but the sacral cornua were not palpable in four babies (15%). The
      PSISs and sacral cornua were easily visualized using ultrasound in all
      participants. The mean distance between the two left and right PSISs was 3.4 +/-
      0.5 cm; the mean distance between the PSISs and cornu was 2.5 +/- 0.5 cm on the
      left and right. CONCLUSION: This study showed that the current landmark
      (equilateral triangle) for infant caudal anesthesia is unreliable. Importantly,
      the sacral hiatus is clinically identifiable only if the sacral cornua are
      palpable; otherwise, using ultrasound is essential.

PMID- 25597343
TI  - The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox
      Drug Efficacy.
AB  - As a result of the conducted experimental studies on intranasal challenge of ICR
      mice, rabbits and miniature pigs (even in the maximum variant) with the doses of
      4.0-5.5 lg PFU of monkeypox virus (MPXV), some clinical signs such as purulent
      conjunctivitis, blepharitis and ruffled fur were found only in mice. The 50%
      infective dose (C ID50 ) of MPXV for these animals estimated by the presence of
      external clinical signs was 4.8 lg PFU, and L ID50 estimated by the virus
      presence in the lungs of mice 7 days post-infection taking into account its 10%
      application in the animal respiratory tract was 1.4 lg PFU. When studying the
      dynamics of MPXV propagation in mice challenged intranasally with 25 L ID50 of
      MPXV, the maximum pathogen accumulation was revealed in nasal cavity, lungs and
      brain: 5.7 +/- 0.1, 5.5 +/- 0.1 and 5.3 +/- 0.3 lg PFU/ml, respectively. The
      pathomorphological examination of these animals revealed the presence and
      replication of the pathogen in the traditional primary target cells for MPXV
      (mononuclear phagocyte system cells and respiratory tract epitheliocytes) as well
      as in some other types of cells (endothelial cells, reticular cells, connective
      tissue cells). Our use of these animals to assess the antiviral efficacy of some
      drugs demonstrated the agreement of the results (a significant positive effect of
      NIOCH-14 and ST-246) with those described in scientific literature, which opens
      up the prospects of using ICR mice as animal models for monkeypox to develop
      preventive antismallpox drugs. 

PMID- 25597344
TI  - Alkaline phosphatase: better than PTH as a marker of cardiovascular and bone
      disease?

PMID- 25597345
TI  - AuAg nanosheets assembled from ultrathin AuAg nanowires.
AB  - Assembly of noble metal nanocrystals into free-standing two-dimensional (2D)
      nanostructures with a regular shape is still a challenge. Here we report the
      preparation of a novel 2D AuAg nanosheet with length of 1.50 +/- 0.30 MUm, width
      of 510 +/- 160 nm, and thickness of ~100 nm via the assembly of ultrathin AuAg
      nanowires in the presence of the triblock copolymer Pluronic P123. The self
      assembly of P123 and the fusion behavior of the nanowires during the assembly
      process are the key reasons for the formation of AuAg nanosheets in P123.
      Furthermore, the obtained AuAg nanosheet@P123 is used as the active material in a
      memory device that exhibits the write-once-read-many-times memory behavior. 

PMID- 25597347
TI  - Large area high-speed metrology SPM system.
AB  - We present a large area high-speed measuring system capable of rapidly generating
      nanometre resolution scanning probe microscopy data over mm(2) regions. The
      system combines a slow moving but accurate large area XYZ scanner with a very
      fast but less accurate small area XY scanner. This arrangement enables very large
      areas to be scanned by stitching together the small, rapidly acquired, images
      from the fast XY scanner while simultaneously moving the slow XYZ scanner across
      the region of interest. In order to successfully merge the image sequences
      together two software approaches for calibrating the data from the fast scanner
      are described. The first utilizes the low uncertainty interferometric sensors of
      the XYZ scanner while the second implements a genetic algorithm with multiple
      parameter fitting during the data merging step of the image stitching process.
      The basic uncertainty components related to these high-speed measurements are
      also discussed. Both techniques are shown to successfully enable high-resolution,
      large area images to be generated at least an order of magnitude faster than with
      a conventional atomic force microscope. 

PMID- 25597346
TI  - Multiple mechanisms influencing the relationship between alcohol consumption and
      peer alcohol use.
AB  - BACKGROUND: Alcohol consumption is typically correlated with the alcohol use
      behaviors of one's peers. Previous research has suggested that this positive
      relationship could be due to social selection, social influence, or a combination
      of both processes. However, few studies have considered the role of shared
      genetic and environmental influences in conjunction with causal processes.
      METHODS: This study uses data from a sample of male twins (N = 1,790) who
      provided retrospective reports of their own alcohol consumption and their peers'
      alcohol-related behaviors, from adolescence into young adulthood (ages 12 to 25).
      Structural equation modeling was employed to compare 3 plausible models of
      genetic and environmental influences on the relationship between phenotypes over
      time. RESULTS: Model fitting indicated that one's own alcohol consumption and the
      alcohol use of one's peers are related through both genetic and shared
      environmental factors and through unique environmental causal influences. The
      relative magnitude of these factors, and their contribution to covariation,
      changed over time, with genetic factors becoming more meaningful later in
      development. CONCLUSIONS: Peers' alcohol use behaviors and one's own alcohol
      consumption are related through a complex combination of genetic and
      environmental factors that act via correlated factors and the complementary
      causal mechanisms of social selection and influence. Understanding these
      processes can inform risk assessment as well as improve our ability to model the
      development of alcohol use.

PMID- 25597350
TI  - Direct synthesis of pure single-crystalline Magneli phase Ti8O15 nanowires as
      conductive carbon-free materials for electrocatalysis.
AB  - The Magneli phase Ti8O15 nanowires (NWs) have been grown directly on a Ti
      substrate by a facile one-step evaporation-deposition synthesis method under a
      hydrogen atmosphere. The Ti8O15 NWs exhibit an outstanding electrical
      conductivity at room temperature. The electrical conductivity of a single Ti8O15
      nanowire is 20.6 S cm(-1) at 300 K. Theoretical calculations manifest that the
      existence of a large number of oxygen vacancies changes the band structure,
      resulting in the reduction of the electronic resistance. The Magneli phase Ti8O15
      nanowires have been used as conductive carbon-free supports to load Pt
      nanoparticles for direct methanol oxidation reaction (MOR). The Pt/Ti8O15 NWs
      show an enhanced activity and extremely high durability compared with commercial
      Pt/C catalysts. 

PMID- 25597348
TI  - Feather-like Ag@TiO2 nanostructures as plasmonic antenna to enhance
      optoelectronic performance.
AB  - The feather-like Ag@TiO2 nanostructures including 1-dimensional (1D) Ag nanowires
      and 2-dimensional (2D) TiO2 possess the features of fast electron transmission by
      one-dimensional metal nanomaterials, high light harvesting and electron
      collection by feather-like nanostructures like "plasmonic antenna" at the same
      time. We introduce them into photoanodes to enhance the conversion efficiency in
      DSSCs. The best efficiency (eta) of the electrode reaches 8.16% compared with
      that of the pure TiO2 electrode (6.41%). The energy conversion efficiency and
      photocurrent density of photoanodes with Ag@TiO2 nanostructures are enhanced by
      about 14.5% and 27.8%, respectively, as compared with those of the pure TiO2
      cells. The photoelectric properties of electrodes are investigated by optical and
      electrochemical measurements. Hence, the improved performances are attributed to
      the "plasmonic antenna" effect due to Ag@TiO2 anchored in TiO2 films. 

PMID- 25597349
TI  - Cationic fluorescent polymer core-shell nanoparticles for encapsulation,
      delivery, and non-invasively tracking the intracellular release of siRNA.
AB  - A multifunctional nanocarrier for encapsulation and delivery of short interfering
      RNA (siRNA) has been realized using cationic fluorescent polymer core-shell
      nanoparticles. The nanocarrier has good biocompatibility and high transfection
      efficiency over the most popular transfection reagent, Lipofectamine 2000.
      Fluorescence resonance energy transfer within the nanocarrier provides a non
      invasive and label-free method to track the intracellular release of siRNA. 

PMID- 25597351
TI  - Regulation of the MAPK pathway by raf kinase inhibitory protein.
AB  - The Raf kinase inhibitor protein 1 (RKIP-1) was the first reported endogenous
      inhibitor of Raf-1-MEK-ERK/MAPK cascade, by interfering with the phosphorylation
      of MEK by Raf-1. However, RKIP's functions related to the MAPK signaling are far
      more complex. Newer data indicate that by modulating different protein-protein
      interactions, RKIP is involved in fine-tuning cell signaling, modulating ERK
      dynamics, and regulating cross talk between different pathways. Here, we describe
      the molecular mechanisms by which RKIP controls MAPK signaling at different
      levels and vice versa and its regulation via feedback phosphorylation. We also
      focus on several discrepancies and questions that remain, such as the RKIP
      binding regulation by Raf-1 N-region phosphorylation, the possible B-Raf
      inhibition, and the effects of RKIP-lipid binding. We also describe how RKIP's
      role as key signaling modulator of many cell fate decisions leads to the fact
      that fine control of RKIP activity and regulation is crucial to avoid
      pathological processes, such as metastasis, pulmonary arterial hypertension, and
      heart failure. 

PMID- 25597352
TI  - Genetic and epigenetic control of RKIP transcription.
AB  - Raf kinase inhibitory protein (RKIP) is known to modulate key signaling cascades
      and regulate normal physiological processes such as cellular proliferation,
      differentiation, and apoptosis. The expression of RKIP is found to be
      downregulated in several cancer metastases and the repressed RKIP expression can
      be reactivated on treatment with chemotherapeutic agents. RKIP is a proven tumor
      metastasis suppressor gene and investigating the mechanisms of transcriptional
      regulation of RKIP is therefore of immense clinical importance. In this review,
      we discuss the basal expression of RKIP in various tissues and the genetic
      aspects of the RKIP chromosomal locus including the structure of the RKIP
      promoter as well as gene regulatory elements such as enhancers. We also review
      the genetic and epigenetic modulation of RKIP transcription through EZH2, a
      component of the polycomb repressive complex 2 (PRC2) and sequence specific
      transcription factors (TFs) BACH1 and Snail. Emerging experimental evidence
      supports a unifying model in which both these TFs repress RKIP transcription in
      cancers by recruiting the EZH2 containing repressive complex to the proximal RKIP
      promoter. Finally, we review the known mechanisms employed by different types of
      chemotherapeutic agents to activate RKIP expression in cancer cells. 

PMID- 25597355
TI  - Survey of Raf kinase inhibitor protein (RKIP) in multiple cancer types.
AB  - Raf kinase inhibitor protein (RKIP), an inhibitor of several signaling pathways,
      has been shown to have metastasis suppressor gene activity and promote apoptosis.
      While first identified in prostate cancer, RKIP's anti-metastasis properties have
      now been demonstrated in multiple tumor types. Furthermore, loss of RKIP
      expression is observed in many cancers as they progress. In this review, we
      provide a survey of the many tumor types in which RKIP function or expression has
      been evaluated. Particular attention is focused on the expression of RKIP in
      clinical tissues and its prognostic significance. A PubMed search through May
      2014 identified 56 publications detailing RKIP expression in clinical cancer
      tissues. The majority of studies revealed that loss of RKIP expression has
      prognostic value for overall survival, disease free survival, and presence of
      metastasis for most solid tumor cancers; whereas, RKIP expression correlated with
      tumor grade or stage in approximately only 50% of the publications. In summary,
      RKIP loss is a frequent occurrence in many solid tumor cancers and may serve as a
      viable prognostic biomarker. 

PMID- 25597354
TI  - Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of
      signaling networks in cancer.
AB  - Cancer is one of the deadliest diseases worldwide, accounting for about 8 million
      deaths a year. For solid tumors, cancer patients die as a result of the
      metastatic spread of the tumor to the rest of the body. Therefore, there is a
      clinical need for understanding the molecular and cellular basis of metastasis,
      identifying patients whose tumors are more likely to metastasize, and developing
      effective therapies against metastatic progression. Over the years, Raf kinase
      inhibitory protein (RKIP) has emerged as a natural suppressor of the metastatic
      process, constituting a tool for studying metastasis and its clinical outcomes.
      Here, we review RKIP's role as a metastasis suppressor and the signaling networks
      and genes regulated by RKIP in metastatic, triple-negative breast cancer. We also
      highlight the clinical implications and power of building gene signatures based
      on RKIP-regulated signaling modules in identifying cancer patients that are at
      higher risk for metastases. Finally, we highlight the potential of RKIP as a tool
      for developing new therapeutic strategies in cancer treatment. 

PMID- 25597353
TI  - RKIP-mediated chemo-immunosensitization of resistant cancer cells via disruption
      of the NF-kappaB/Snail/YY1/RKIP resistance-driver loop.
AB  - Cancer remains one of the most dreadful diseases. Whereas most treatment regimens
      for various cancers have resulted in improved clinical responses and sometimes
      cures, unfortunately, subsets of cancer patients are either pretreatment
      resistant or develop resistance following therapy. These subsets of patients
      develop cross-resistance to unrelated therapeutics and usually succumb to death.
      Thus, delineating the underlying molecular mechanisms of resistance of various
      cancers and identifying molecular targets for intervention are the current main
      focus of research investigations. One approach to investigate cancer resistance
      has been to identify pathways that regulate resistance and develop means to
      disrupt these pathways in order to override resistance and sensitize the
      resistant cells to cell death. Hence, we have identified one pathway that is
      dysregulated in cancer, namely, the NF-kappaB/Snail/YY1/RKIP loop, that has been
      shown to regulate, in large part, tumor cell resistance to apoptosis by
      chemotherapeutic and immunotherapeutic cytotoxic drugs. The dysregulated
      resistant loop is manifested by the overexpression of NF-kappaB, Snail, and YY1
      activities and the underexpression of RKIP. The induction of RKIP expression
      results in the downregulation of NF-kappaB, Snail, and YY1 and the sensitization
      of resistant cells to drug-induced apoptosis. These findings identified RKIP, in
      addition to its antiproliferative and metastatic suppressor functions, as an anti
      resistance factor. This brief review describes the role of RKIP in the regulation
      of drug sensitivity via disruption of the NF-kappaB/Snail/ YY1/RKIP loop that
      regulates resistance in cancer cells. 

PMID- 25597356
TI  - Role of Raf kinase inhibitor protein in Helicobacter pylori-mediated signaling in
      gastric cancer.
AB  - Helicobacter pylori is a helical bacterium that colonizes the stomach in over
      half of the world's population. Infection with this bacterium has been linked to
      peptic ulcer disease and gastric cancer. The bacterium has been shown to affect
      regulatory pathways in its host cells through specific virulence factors that
      control gene expression. Infection with H. pylori increases levels of
      phosphorylation of Raf kinase inhibitor protein (pRKIP) in gastric adenocarcinoma
      (AGS) cells in vitro and in vivo. We investigated the role of H. pylori in the
      phosphorylation of RKIP as a possible mechanism to downregulate pro-survival
      signals in gastric adenocarcinoma. pRKIP induces RKIP transcriptional activity,
      which serves to induce apoptosis of damaged cells to prevent further
      tumorigenesis. Infection of wild type and RKIP knockout mice with H. pylori for 2
      months further confirmed roles of RKIP and pRKIP in the prevention of gastric
      cancer progression. Loss of RKIP in AGS cells results in increased expression of
      the Cag A virulence factor after H. pylori infection and RKIP overexpression
      inhibits H. pylori-mediated STAT3 phosphorylation and STAT3 and NF-kappaB
      transcriptional activity. We examined the role of mTOR (mammalian target of
      rapamycin) after H. pylori infection on the phosphorylation of RKIP. Cells
      treated with rapamycin, an inhibitor of mTOR, displayed less expression of pRKIP
      after H. pylori infection. Microarray antibody analysis was conducted on wild
      type and RKIP-knockdown AGS cells and showed that in the absence of RKIP, there
      was increased expression of pro-tumorigenic proteins such as EGFR, Raf-1, and
      MAPKs. Although further work is needed to confirm the interaction of RKIP and
      mTOR in AGS cells as a result of H. pylori infection, we hypothesize that H.
      pylori-mediated induction of pro-survival signaling in gastric epithelial cells
      induces a feedback response through the activation of RKIP. The phosphorylated,
      or active, form of RKIP is important in protecting gastric epithelial cells from
      tumorigenesis after H. pylori infection. 

PMID- 25597358
TI  - RKIP: a governor of intracellular signaling.
AB  - The Raf kinase inhibitor protein (RKIP) increasingly evolves as an important
      regulator of intracellular signaling networks and thus participates in diverse
      physiological functions ranging from growth and differentiation processes to
      muscle contraction. Several molecular events contribute to the ability of RKIP to
      tightly coordinate kinase signaling. The elucidation of the molecular mechanisms
      leading to substrate specificity of RKIP and substrate binding efficacy is of
      great interest for a better understanding of the overall role of RKIP in the
      organism but also for the design of specific and potent kinase inhibitors. In
      this work, we will review mechanistic details of the regulation of RKIP as
      inhibitor of Raf-1 and G protein-coupled receptor kinase 2 (GRK2) that enable
      RKIP to coordinate the cell's balance between inhibition and potentiation of
      mitogenic ERK1/2 signaling--a prominent example of RKIP's function as a regulator
      of intracellular signaling.

PMID- 25597357
TI  - RKIP structure drives its function: a three-state model for regulation of RKIP.
AB  - Raf kinase inhibitory protein (RKIP) is a highly conserved regulator of many
      signaling networks whose loss or inactivation can lead to a variety of disease
      states. The multifaceted roles played by RKIP are enabled by an allosteric
      structure that is controlled through phosphorylation of RKIP and dynamics in the
      RKIP pocket loop. Perhaps the most striking feature of RKIP is that it can assume
      multiple functional states. Specifically, phosphorylation redirects RKIP from a
      state that binds and inhibits Raf-1 to a state that binds and inhibits GRK2.
      Recent evidence suggests the presence of a third functional state that
      facilitates RKIP phosphorylation. Here, we present a three-state model to explain
      the RKIP functional switch and discuss the role of the pocket loop in regulating
      RKIP activity. 

PMID- 25597359
TI  - Interactions of RKIP with inflammatory signaling pathways.
AB  - The inflammatory response plays an important role in host defense and maintenance
      of homeostasis, while imbalances in these responses can also lead to pathologic
      disease processes. Emerging data show that RKIP interacts with multiple signaling
      molecules that may potentiate multiple functions during inflammatory processes.
      Here, we review the interaction of RKIP with both the MAPK and NF-kappaB pathways
      in relation to chronic inflammatory diseases. In these settings, it can both
      inhibit inflammatory pathways as well contribute to pro-inflammatory signaling,
      often depending on the interactions with multiple proteins and perhaps lipids.
      The interactions of RKIP with proteins, phospholipids, fatty acids, and their
      enzymes thus could play a substantial role in diseases like asthma and diabetes.
      Targeting interactions of RKIP with these pathways could lead to novel approaches
      to treatment. 

PMID- 25597361
TI  - The influence of 3D kinematic and electromyographical parameters on cycling
      economy.
AB  - PURPOSE: Economy is considered to be a key factor for the determination of
      performance in endurance events such as cycling. There have been no
      investigations which have related cycling economy to simultaneous measurements of
      3D kinematics and muscular activation. This study examined selected biomechanical
      and neuromuscular parameters which have the strongest association with cycling
      economy. METHODS: Twenty-five trained cyclists (31.27 +/- 3.19 years) completed
      steady state cycling time trials at a workload of 180 W. Simultaneous
      measurements of 3D kinematics and electromyographical parameters were obtained.
      Continuous measurements of expired gases were used to provide a measure of
      cycling economy. RESULTS: A multiple regression analysis showed that key
      parameters of peak knee extension velocity and mean activity of the rectus
      femoris muscles were significant predictors of VO2 during steady state cycling (P
      < 0.01). CONCLUSION: This study has documented the key biomechanical parameters
      pertinent to cycling economy. As economy has been shown to influence aerobic
      performance, future work should focus on optimising these parameters to improve
      cycling economy.

PMID- 25597362
TI  - O-H bond oxidation by a monomeric Mn(III)-OMe complex.
AB  - Manganese-containing, mid-valent oxidants (Mn(III)-OR) that mediate proton
      coupled electron-transfer (PCET) reactions are central to a variety of crucial
      enzymatic processes. The Mn-dependent enzyme lipoxygenase is such an example,
      where a Mn(III)-OH unit activates fatty acid substrates for peroxidation by an
      initial PCET. This present work describes the quantitative generation of the
      Mn(III)-OMe complex, [Mn(III)(OMe)(dpaq)](+) (dpaq = 2-[bis(pyridin-2
      ylmethyl)]amino-N-quinolin-8-yl-acetamidate) via dioxygen activation by
      [Mn(II)(dpaq)](+) in methanol at 25  degrees C. The X-ray diffraction structure
      of [Mn(III)(OMe)(dpaq)](+) exhibits a Mn-OMe group, with a Mn-O distance of
      1.825(4) A, that is trans to the amide functionality of the dpaq ligand. The
      [Mn(III)(OMe)(dpaq)](+) complex is quite stable in solution, with a half-life of
      26 days in MeCN at 25  degrees C. [Mn(III)(OMe)(dpaq)](+) can activate phenolic O
      H bonds with bond dissociation free energies (BDFEs) of less than 79 kcal mol(-1)
      and reacts with the weak O-H bond of TEMPOH (TEMPOH = 2,2'-6,6'
      tetramethylpiperidine-1-ol) with a hydrogen/deuterium kinetic isotope effect (H/D
      KIE) of 1.8 in MeCN at 25  degrees C. This isotope effect, together with other
      experimental evidence, is suggestive of a concerted proton-electron transfer
      (CPET) mechanism for O-H bond oxidation by [Mn(III)(OMe)(dpaq)](+). A kinetic and
      thermodynamic comparison of the O-H bond oxidation reactivity of
      [Mn(III)(OMe)(dpaq)](+) to other M(III)-OR oxidants is presented as an aid to
      gain more insight into the PCET reactivity of mid-valent oxidants. In contrast to
      high-valent counterparts, the limited examples of M(III)-OR oxidants exhibit
      smaller H/D KIEs and show weaker dependence of their oxidation rates on the
      driving force of the PCET reaction with O-H bonds. 

PMID- 25597360
TI  - Raf kinase inhibitory protein (RKIP): functional pleiotropy in the mammalian
      brain.
AB  - In 1984, a cytosolic protein was isolated from bovine brain and coined
      phosphatidylethanolamine binding protein (PEBP) to describe its phospholipid
      binding potential. Its cellular function remained elusive for more than a decade
      until it was discovered that PEBP had the ability to suppress the Raf1-mitogen
      activated protein kinase (MAPK) pathway, earning it the new name of Raf1 kinase
      inhibitory protein (RKIP). This milestone discovery has paved the way for
      numerous studies that have now extended the reach of RKIP's function to other
      signaling cascades, within the context of various physiological and
      pathophysiological systems. This review will summarize our current knowledge of
      the neurophysiological roles of RKIP in the mammalian brain, including its
      function in the circadian clock and synaptic plasticity. It will also discuss
      evidence for an involvement of RKIP and its derived neuropeptide, hippocampal
      cholinergic neurostimulating peptide (HCNP), in neural development and
      differentiation. Implications in certain pathologies such as Alzheimer's disease
      and brain cancer will be highlighted. By chronicling the diverse functions of
      RKIP in the brain, we hope that this review will serve as a timely resource that
      ignites future studies on this versatile, multifaceted protein in the nervous
      system. 

PMID- 25597363
TI  - Rapidly prototyped multi-scale electrodes to minimize the voltage requirements
      for bacterial cell lysis.
AB  - Lab-on-a-chip systems used for nucleic acid based detection of bacteria rely on
      bacterial lysis for the release of cellular material. Although electrical lysis
      devices can be miniaturized for on-chip integration and reagent-free lysis, they
      often suffer from high voltage requirements, and rely on the use of off-chip
      voltage supplies. To overcome this barrier, we developed a rapid prototyping
      method for creating multi-scale electrodes that are structurally tuned for
      lowering the voltage needed for electrical bacterial lysis. These three
      dimensional multi-scale electrodes - with micron scale reaction areas and
      nanoscale features - are fabricated using benchtop methods including craft
      cutting, polymer-induced wrinkling, and electrodeposition, which enable a lysis
      device to be designed, fabricated, and optimized in a matter of hours. These
      tunable electrodes show superior behaviour compared to lithographically-prepared
      electrodes in terms of lysis efficiency and voltage requirement. Successful
      extraction of nucleic acids from bacterial samples processed by these electrodes
      demonstrates the potential for these rapidly prototyped devices to be integrated
      within practical lab-on-a-chip systems.

PMID- 25597364
TI  - Photogenerated lophyl radicals in 1-alkyl-3-vinylimidazolium
      bis(trifluoromethylsulfonyl)imides.
AB  - 1-Alkyl-3-vinylimidazolium bis(trifluoromethylsulfonyl)imides were investigated
      as a matrix for photogenerated lophyl radicals obtained by irradiation of o
      chlorohexaarylbisimidazole (o-Cl-HABI). Photoinduced polymerization of ionic
      liquid monomers using the photoinitiator system composed of o-Cl-HABI and 3
      mercapto-1,2,4-4H-triazole was investigated by photo-DSC. Selected thermal
      properties and viscosity of these ionic liquid monomers are important to
      understand the lophyl radical kinetics after exposure. Solvent cage effects and
      viscosity of the ionic liquid monomers strongly affect radical recombination in
      the dark. This was investigated at different temperatures. The rate constant for
      radical recombination (krec) decreases from the methyl to the butyl substituted
      ionic liquid monomer. This may be attributed to an increasing viscosity with
      increasing size of the alkyl substituent. However, further increase in the size
      of the alkyl substituent from a butyl to a heptyl group bound at the imidazolium
      ion results in an increase of krec although the viscosity does further increase.
      Therefore, a minimum in krec was found for the butyl substituted ionic liquid
      monomer. Furthermore, the Eyring parameters indicated a dependence on the chain
      length of the alkyl substituent bound at the imidazolium ion while the activation
      energy of the viscous flow only slightly changes. Furthermore, the size of the
      alkyl substituent bound at the cation of the ionic liquid monomers strongly
      influences both solvent cage and viscosity, and therefore, the concentration of
      lophyl radicals during photoinduced generation. Photo-induced polymerization of
      the ionic liquid monomers is affected by viscosity at low conversion and by
      vitrification at higher conversion. The latter is important for application of
      the ionic liquid monomers and the polymers made from them by photoinduced
      polymerization.

PMID- 25597365
TI  - The experiences of Russian-speaking migrants in primary care consultations.
AB  - BACKGROUND: Some three million Russian-speaking immigrants from the former Soviet
      Union live in Germany today. Many of them underwent a different kind of medical
      socialization than the indigenous population, but the experiences and
      expectations of this group of patients have hardly been studied to date. METHODS:
      In a qualitative study, 24 chronically ill native Germans and 25 chronically ill
      Russian-speaking immigrants were recruited via notices, through their primary
      care physicians, and by word of mouth and underwent a semistructured interview in
      their mother tongue (German or Russian) about their experiences with their
      primary care physicians. The interviews were recorded using an audio device,
      translated into German if necessary, and transcribed, and their content was
      analyzed with the MAXQDA software package. RESULTS: The immigrants were less
      satisfied with their primary care physicians than the native Germans. This
      manifested itself in a weaker patient-physician connection and frequent changes
      of physician due to dissatisfaction with treatment. Both groups considered
      themselves inadequately informed about matters of health, but they gave differing
      reasons for this. On the other hand, the participants in both groups had
      practically the same general expectations from their primary care physicians.
      However, detailed analysis revealed cultural differences. CONCLUSION: Physicians
      in Germany should be more aware of the culturally based expectations of immigrant
      patients in order to understand their needs better, improve the physician-patient
      relationship, and ensure equal opportuities in health care. For example, many
      immigrants would prefer their doctors to communicate with them in a manner that
      non-immigrants would consider paternalistic.

PMID- 25597366
TI  - The conservative and interventional treatment of fibroids.
AB  - BACKGROUND: Fibroids are the most common benign tumors in women. One-third of all
      women of reproductive age undergo treatment for symptomatic fibroids. In recent
      years, the spectrum of available treatments has been widened by the introduction
      of new drugs and interventional procedures. METHODS: Selective literature review
      on the treatment of uterine fibroids, including consideration of several Cochrane
      Reviews. RESULTS: Fibroids can be treated with drugs, interventional procedures
      (uterine artery embolization [UAE] and focused ultrasound treatment [FUS]), and
      surgery. The evidence regarding the various available treatments is mixed. All
      methods improve symptoms, but only a few comparative studies have been performed.
      A meta-analysis revealed that recovery within 15 days is more common after
      laparoscopic enucleation than after open surgery (odds ratio [OR], 3.2). A
      minimally invasive hysterectomy, or one performed by the vaginal route, is
      associated with a shorter hospital stay and a more rapid recovery than open
      transabdominal hysterectomy. UAE is an alternative to hysterectomy for selected
      patients. The re-intervention rates after fibroid enucleation, hysterectomy, and
      UAE are 8.9-9%, 1.8-10.7%, and 7-34.6%, respectively. The main drugs used to
      treat fibroids are gonadotropin-releasing hormone analogs and selective
      progesterone receptor modulators. CONCLUSION: Multiple treatment options are
      available and enable individualized therapy for symptomatic fibroids. The most
      important considerations in the choice of treatment are the question of family
      planning and, in some cases, the technical limitations of the treatments
      themselves.

PMID- 25597367
TI  - Dislocation following total hip replacement.
AB  - BACKGROUND: Hip replacement ranks among the more successful operations on the
      musculoskeletal system, but it can have serious complications. A common one is
      dislocation of the total hip endoprosthesis, an event that arises in about 2% of
      patients within 1 year of the operation. Physicians should be aware of how this
      problem can be prevented and, if necessary, treated, so that the degree of trauma
      due to hip dislocation after hip replacement surgery can be kept to a minimum.
      METHODS: The authors searched Medline selectively for pertinent publications and
      analyzed the annual reports of international endoprosthesis registries. RESULTS:
      The rate of dislocation of primary hip replacements ranges from 0.2% to 10% per
      year, while that of artificial hip joints that have already been surgically
      revised can be as high as 28%, depending on the patient population, the follow-up
      interval, and the type of prosthesis. Patient-specific risk factors for
      displacement of a hip endoprosthesis include advanced age, accompanying
      neurologic disease, and impaired compliance. Patients should scrupulously avoid
      hip movements such as bending far forward from a standing position, or internal
      rotation of the flexed hip. Operation-specific risk factors include suboptimal
      implant position, insufficient soft-tissue tension, and inadequate experience of
      the surgeon. Conservative treatment is justified the first time dislocation
      occurs without any identifiable cause. If a mechanical cause of instability is
      found, then operative revision should be performed as recommended in a
      standardized treatment algorithm, because, otherwise, dislocation is likely to
      recur. CONCLUSION: The dislocation of a total hip endoprosthesis is an
      emotionally traumatizing event that should be prevented if possible. Preoperative
      risk assessment should be performed and the operation should be performed with
      optimal technique, including the best possible physical configuration of implant
      components, soft-tissue balance, and an adequately experienced orthopedic
      surgeon.

PMID- 25597368
TI  - The structural influence of family and parenting on young people's sexual and
      reproductive health in rural northern Tanzania.
AB  - This paper explores the structural role of the family and parenting in young
      people's sexual and reproductive health. The study involved eight weeks of
      participant observation, 26 in-depth interviews, and 11 group discussions with
      young people aged 14-24 years, and 20 in-depth interviews and 6 group discussions
      with parents/carers of children in this age group. At an individual level,
      parenting and family structure were found to affect young people's sexual
      behaviour by influencing children's self-confidence and interactional competence,
      limiting discussion of sexual health and shaping economic provision for children,
      which in turn affected parental authority and daughters' engagement in risky
      sexual behaviour. Sexual norms are reproduced both through parents' explicit
      prohibitions and their own behaviours. Girls are socialised to accept men's
      superiority, which shapes their negotiation of sexual relationships.
      Interventions to improve young people's sexual and reproductive health should
      recognise the structural effects of parenting, both in terms of direct influences
      on children and the dynamics by which structural barriers such as gendered power
      relations and cultural norms around sexuality are transmitted across generations.

PMID- 25597370
TI  - Electroretinographic and optical coherence tomography findings in breast cancer
      patients using aromatase inhibitors.
AB  - BACKGROUND: The present cross-sectional study has the purpose to investigate the
      impact of aromatase inhibitors (AIs) on retinal nerve fiber layer (RNFL)
      thickness, optic nerve and macular function in patients using AIs for breast
      cancer treatment. METHODS: Participants in our study were 41 hormone-receptor
      positive earlystage breast cancer patients who were treated with AIs in the
      adjuvant setting. Moreover, 40 age- and gender-matched control subjects, having
      neither ocular nor systemic disorders, were included in this study. All
      participants underwent a complete ophthalmological examination, including best
      corrected visual acuity (BCVA) assessment, RNFL thickness and central foveal
      thickness (CFT) measurement, visual evoked potentials (VEP) recording and
      multifocal-electroretinogram (mf-ERG) recording. Univariate and multiple
      regression analyses were performed. RESULTS: At the multiple regression analyses,
      patients receiving AIs presented with lower average RNFL and inferior RNFL.
      Moreover, similarly to the univariate analysis, intake of AIs was associated with
      lower amplitude P100, lower retinal response density in ring 1 and ring 2, longer
      peak time P100 and longer P1 time in ring 1. CONCLUSION: Our study is the first
      in the literature investigating the potential effect of AIs on RNFL thickness,
      optic nerve and macular function in patients using AIs for breast cancer
      treatment. The principal message of our study is that patients using AIs
      exhibited a significant decrease in RNFL thickness (average, superior and
      inferior), retinal response density and visual acuity compared to healthy
      controls, while VEP findings (both amplitude and peak time of P100) differ
      significantly as well.

PMID- 25597371
TI  - The effect of gatifloxacin 0.3% or moxifloxacin 0.5% on corneal healing, ocular
      tolerability and toxicity following pterygium surgery.
AB  - PURPOSE: To compare the rate of corneal epithelial healing and ocular
      tolerability following pterygium surgery between gatifloxacin and moxifloxacin.
      METHODS: In this double masked, prospective, controlled study 40 patients were
      randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5%
      following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post
      operatively or until complete corneal epithelial healing. The primary outcome
      measure was the area of corneal epithelial defect during the post-operative
      period. Patients graded post-operative ocular pain, foreign body sensation,
      tearing, general burning sensation and burning sensation post-antibiotic drops
      instillation on a scale of 1-5. Conjunctival hyperemia and superficial punctate
      keratopathy (SPK) were measured on a scale of 0-3. RESULTS: No significant
      differences between groups were found in terms of corneal epithelial defect
      percentage over time (p = 0.989) and there was no significant difference between
      groups on each of the post-operative days. No significant differences were noted
      in terms of post-operative ocular pain, foreign body sensation, tearing, general
      burning sensation, burning sensation post-antibiotic drops instillation,
      conjunctival hyperemia and SPK. CONCLUSIONS: Gatifloxacin and moxifloxacin showed
      equivalent results in terms of corneal epithelial healing and ocular tolerability
      following pterygium surgery. This study suggests that there was no apparent added
      epithelial toxicity due to the presence of benzalkonium chloride in the
      gatifloxacin preparation when compared to moxifloxacin.

PMID- 25597369
TI  - Intramuscular midazolam versus intravenous lorazepam for the prehospital
      treatment of status epilepticus in the pediatric population.
AB  - OBJECTIVE: To examine the effectiveness of intramuscular (IM) midazolam versus
      intravenous (IV) lorazepam for the treatment of pediatric patients with status
      epilepticus (SE) in the prehospital care setting. METHODS: This multicenter
      clinical trial randomized patients diagnosed with SE to receive either IM
      midazolam or IV lorazepam administered by paramedics in the prehospital care
      setting. Included in this secondary analysis were only patients younger than 18
      years of age. Evaluated were the associations of the treatment group (IM vs. IV)
      with the primary outcome, defined as seizure cessation prior to emergency
      department (ED) arrival, and with patient characteristics, time to important
      events, and adverse events. Descriptive statistics and 99% confidence intervals
      (CIs) were used for the analysis. RESULTS: Of 893 primary study subjects, 120 met
      criteria for this study (60 in each treatment group). There were no differences
      in important baseline characteristics or seizure etiologies between groups. The
      primary outcome was met in 41 (68.3%) and 43 (71.7%) of subjects in the IM and IV
      groups, respectively (risk difference [RD] -3.3%, 99% CI -24.9% to 18.2%).
      Similar results were noted for those younger than 11 years (RD -1.3%, 99% CI 
      25.7% to 23.1%). Time from initiating the treatment protocol was shorter for
      children who received IM midazolam, mainly due to the shorter time to administer
      the active treatment. Safety profiles were similar. SIGNIFICANCE: IM midazolam
      can be rapidly administered and appears to be safe and effective for the
      management of children with SE treated in the prehospital setting. The results
      must be interpreted in the context of the secondary analysis design and sample
      size of the study.

PMID- 25597372
TI  - Multimodal imaging in paclitaxel-induced macular edema: the microtubule
      disfunction.
AB  - Taxanes are a rare cause of macular edema. A 63-year-old female, under paclitaxel
      treatment, was observed with progressively bilateral visual acuity loss and an
      apparently normal fundus. Optical coherence tomography revealed a bilateral
      cystoid macular edema with a late petaloid pooling on fluorescein angiography.
      Fundus autofluorescence exhibited a foveal hiperautofluorescent pattern. There
      was a great improvement of visual acuity and macular thickness after 5 months of
      drug withdrawal. Paclitaxel maculopathy diagnosis requires a high degree of
      suspicion. The pathophysiology remains unclear. 

PMID- 25597373
TI  - The effect of cigarette smoking on retinal nerve fiber layer thickness in
      patients with migraine.
AB  - CONTEXT: Migraine is a frequent and disabling chronic neurological condition with
      complex pathophysiology. Both cigarette smoking and migraine may cause damage to
      the optic nerve. OBJECTIVE: The primary objective of this study was to
      investigate the effect of cigarette smoking on retinal nerve fiber layer (RNFL)
      thickness in patients with migraine. MATERIALS AND METHODS: Eighty-four
      consecutive patients diagnosed with migraine (34 smokers and 50 nonsmokers) and
      66 age- and gender-matched healthy non-smoker controls were enrolled for this
      observational cross-sectional study. RNFL thickness was measured using spectral
      domain optical coherence tomography (OCT) and then RNFL thickness in patients
      with migraine who smoke was compared to nonsmoking patients with migraine and
      healthy subjects. RESULTS: The average, superior, nasal and inferior RNFL
      thicknesses were significantly thinner in patients with migraine compared to the
      control group (p < 0.001, p = 0.02, p < 0.001 and p = 0.04, respectively). The
      average and inferior RNFL thicknesses were significantly reduced in smoker
      patients with migraine compared to the nonsmokers (p = 0.011, p = 0.045,
      respectively). Nonsmoker patients with migraine had significantly thinner average
      and nasal RNFL thicknesses than the control group (p = 0.001, p = 0.001,
      respectively). CONCLUSION: Cigarette smoking may cause significant RNFL thinning
      in patients with migraine. OCT may be a feasible technique for determination of
      smoking-induced ocular damage in patients with migraine.

PMID- 25597374
TI  - Half-and-half nails in a pediatric patient after chemotherapy.
AB  - Half-and-half nail, characterized by a reddish brown distal band with a sharply
      demarcated white proximal band, is a specific manifestation of chronic kidney
      disease, but it is unusual to occur after chemotherapy. We report a seven-year
      old girl who developed half-and-half nails in her fingers one month after
      treatment with modified Berlin-Frankfurt-Munster protocol followed by maintenance
      therapy with oral methotrexate and 6-mercaptopurine for pre-B acute lymphoblastic
      leukemia. 

PMID- 25597375
TI  - Reduced central corneal thickness in patients with isotretinoin treatment.
AB  - CONTEXT: It is well known that oral isotretinoin treatment causes numerous ocular
      side-effects. OBJECTIVE: To investigate the effect of systemic isotretinoin
      treatment on central corneal thickness (CCT) values due to meibomian gland
      disease (MGD). PARTICIPANTS: In this prospective study, 47 patients (27 men, 20
      women) with nodulocystic acne vulgaris treated with oral isotretinoin (0.8 mg/kg
      daily) were included. METHODS: All patients were analyzed with the Pentacam
      Scheimpflug topography at baseline, on the 3rd and 6th month of treatment. Main
      outcome measures were MGD scores and CCT. RESULTS: The mean age of patients was
      25.1 +/- 4.4 years. The mean MGD scores were significantly higher at 3rd month
      (1.3 +/- 0.9) and 6th month (1.5 +/- 1.0) of treatment compared with baseline
      (1.1 +/- 0.9) (p < 0.001). The mean CCT value at baseline was 540.5 +/- 22.1 um;
      536.9 +/- 20.5 um at 3rd month and 531.4 +/- 22.2 um at 6th month. The
      differences between baseline and 6th month CCT measurements were statistically
      significant (p < 0.001). There was negative correlation between mean MGD scores
      and CCT values at the 6th month of treatment which was statistically significant
      (p = 0.038, r = -0.221). CONCLUSION: Isotretinoin treatment causes higher MGD
      scores. A statistically significant decrease in CCT due to MGD was detected at
      6th month of treatment.

PMID- 25597376
TI  - The effect of rebreathing and hyperventilation on retinal and choroidal vessels
      measured by spectral domain optical coherence tomography.
AB  - OBJECTIVE: The purpose of this study was to examine the vasoreactivity in retina
      and choroid of the healthy eyes in response to experimentally altered partial
      arterial pressure of carbon dioxide (PaCO(2)) using a non-invasive technique,
      spectral domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: The
      study included non-smoking participants between 18 and 35 years of age, having
      visual acuity of 20/20 and with no systemic and ocular diseases. At baseline, the
      participants breathed room air (normocapnia). Hypocapnia was created with the
      help of hyperventilation; for this, the participants were instructed to draw deep
      and quick breaths, resulting one breathing cycle per 2 s. To create hypercapnia
      subjects rebreathed from a 5 l bag at least 3 min. Choroidal thickness and
      retinal artery diameter were measured at baseline, and hyperventilation and
      rebreathing conditions by SD-OCT. RESULTS: Twenty eyes of 20 healthy subjects
      were included in this study. Their mean age was 24.90 +/- 5.32 years.
      Hyperventilation caused a significant reduction in choroidal thickness, compared
      with baseline, at all points; whereas rebreathing caused no significant change at
      all points. The mean diameters of the arteries were 151.80 +/- 7.88 MUm, with a
      significant decline to 148.90 +/- 7.25 MUm at hyperventilation condition and a
      significant increase to 153.50 +/- 7.88 MUm at rebreathing condition (p = 0.018,
      p = 0.043, respectively). CONCLUSION: This study demonstrated that, SD-OCT was a
      useful tool in measuring the ocular vascular response under hypercapnia and
      hypocapnia conditions. These findings may be helpful for further understanding
      the physiological nature of ocular blood flow and this preliminary study provides
      a basis for future studies.

PMID- 25597378
TI  - Crystalline and liquid structure of zinc chloride trihydrate: a unique ionic
      liquid.
AB  - The water/ZnCl(2) phase diagram in the vicinity of the 75 mol % water composition
      is reported, demonstrating the existence of a congruently melting phase. Single
      crystals of this 3-equiv hydrate were grown, and the crystal structure of
      [Zn(OH(2))(6)][ZnCl(4)] was determined. Synchrotron X-ray and neutron diffraction
      and IR and Raman spectroscopy along with reverse Monte Carlo modeling demonstrate
      that a CsCl-type packing of the molecular ions persists into the liquid state.
      Consistent with the crystalline and liquid structural data, IR spectroscopy
      demonstrates that the O-H bonds of coordinated water do not exhibit strong
      intermolecular hydrogen ion bonding but are significantly weakened because of the
      water's coordination to Lewis acidic zinc ions. The O-H bond weakening makes this
      system a very strong hydrogen-bond donor, whereas the ionic packing along with
      the nonpolar geometry of the molecular ions makes this system a novel nonpolar,
      hydrogen-bonding, ionic liquid solvent.

PMID- 25597377
TI  - Optimisation of a dosing regime for a topical skin protectant (barrier cream).
AB  - CONTEXT: Topical skin protectants (barrier creams) have the potential to reduce
      or enhance the severity of dermal lesions following exposure to allergens or
      irritants. Therefore, it is essential that such products are subject to
      appropriate clinical evaluation prior to marketing. Consequently, it is important
      to accurately define a dosing regime in order to assess test products under
      appropriate conditions. OBJECTIVE: In this study, we extended the use of a
      standard rubefacient (methyl nicotinate; MN) assay to establish the optimum
      thickness and duration of action of a novel barrier cream (RD1433). White
      petroleum jelly (Vaseline((r))) was used as a comparator product. METHODS: The
      dermal response to MN was measured on the volar forearm skin of volunteers (n =
      12; average age 47.5 years) using an array of biophysical instruments and visual
      scoring. When applied at a nominal thickness of 0.1 mm, RD1433 retained
      effectiveness against MN for up to six hours. In contrast, Vaseline((r)) was
      relatively ineffective. Moreover, RD1433 provoked no measurable signs of
      irritation and so can be considered acceptable for further clinical evaluation.
      CONCLUSION: Future clinical studies using RD1433 should be based on topical
      application of a 0.1 mm thickness layer every six hours.

PMID- 25597380
TI  - Increasing thyroid cancer incidence in Queensland, Australia 1982-2008 - true
      increase or overdiagnosis?
AB  - BACKGROUND: Thyroid cancer incidence has been increasing worldwide. Some suggest
      greater ascertainment of indolent tumours is the only driver, but others suggest
      there has been a true increase. Increases in Australia appear to have been among
      the largest in the world, so we investigated incidence trends in the Australian
      state of Queensland to help understand reasons for the rise. METHODS: Thyroid
      cancers diagnoses in Queensland 1982-2008 were ascertained from the Queensland
      Cancer Registry. We calculated age-standardized incidence rates (ASR) and used
      Poisson regression to estimate annual percentage change (APC) in thyroid cancer
      incidence by socio-demographic and tumour-related factors. RESULTS: Thyroid
      cancer ASR in Queensland increased from 2.2 to 10.6/100 000 between 1982 and 2008
      equating to an APC of 5.5% [95% confidence interval (CI) 4.7-6.4] in men and 6.1%
      (95% CI 5.5-6.6) in women. The rise was evident, and did not significantly
      differ, across socio-economic and remoteness-of-residence categories. The largest
      increase seen was in the papillary subtype in women (APC 7.9%, 95% CI 7.3-8.5).
      Incidence of localized and more advanced-stage cancers rose over time although
      the increase was greater for early-stage cancers. CONCLUSION: There has been a
      marked increase in thyroid cancer incidence in Queensland. The increase is
      evident in men and women across all adult age groups, socio-economic strata and
      remoteness-of-residence categories as well as in localized and more advanced
      stage cancers. Our results suggest 'overdiagnosis' may not entirely explain
      rising incidence. Contemporary aetiological data and individual-level information
      about diagnostic circumstances are required to further understand reasons for
      rising thyroid cancer incidence.

PMID- 25597381
TI  - Sample preparation: a crucial factor for the analytical performance of rationally
      designed MALDI matrices.
AB  - Evidence is presented that the performance of the rationally designed MALDI
      matrix 4-chloro-alpha-cyanocinnamic acid (ClCCA) in comparison to its well
      established predecessor alpha-cyano-4-hydroxycinnamic acid (CHCA) is
      significantly dependent on the sample preparation, such as the choice of the
      target plate. In this context, it becomes clear that any rational designs of
      MALDI matrices and their successful employment have to consider a larger set of
      physicochemical parameters, including sample crystallization and
      morphology/topology, in addition to parameters of basic (solution and/or gas
      phase) chemistry. 

PMID- 25597382
TI  - Recognising pitfalls in assessment of tumours by diffusion-weighted MRI: a
      pictorial essay.
AB  - Diffusion-weighted imaging (DWI) has become an integral part of MRI. Knowledge of
      the basic principles of DWI and its pitfalls are imperative in the proper
      application of this technique. We illustrate potential pitfalls of DWI in
      oncologic imaging. 

PMID- 25597383
TI  - Second-generation antipsychotic effect on cognition in patients with
      schizophrenia--a meta-analysis of randomized clinical trials.
AB  - OBJECTIVE: To investigate the effect of second-generation antipsychotics on
      cognitive function in patients diagnosed with schizophrenia or schizoaffective
      disorder. METHOD: Multiple-treatments meta-analysis model. RESULTS: On cognitive
      composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95%
      CI: 0.12-1.63, quetiapine, ES 0.75; 95% CI: 0.00-1.49, and first-generation
      antipsychotics (FGAs), ES 0.89; 95% CI: 0.14-1.64. Analyses on each cognitive
      domain showed clozapine, ES 0.37; 95% CI: 0.00-0.74, olanzapine, ES 0.31; 95%CI:
      0.02-0.59, quetiapine, ES 0.34; 95% CI: 0.03-0.64, and FGAs, ES 0.51; 95% CI:
      0.18-0.83 performing poorer on verbal working memory than ziprasidone, as well as
      FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04-0.58. On executive
      function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06-1.58,
      olanzapine, ES 0.81; 95% CI: 0.07-1.55, quetiapine, ES 0.76; 95% CI: 0.02-1.51,
      ziprasidone, ES 0.90; 95% CI: 0.14-1.67, and FGAs, ES 0.83; 95% CI: 0.08-1.58. On
      processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02
      1.91, and quetiapine, ES 0.36; 95% CI: 0.01-0.72. On long-term verbal working
      memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06-0.76.
      On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01
      0.50, and clozapine, ES 0.44; 95% CI: 0.06-0.81. Lastly, FGAs, ES 0.41; 95% CI:
      0.04-0.78, and clozapine, ES 0.44; 95% CI: 0.05-0.83, performed poorer on
      visuospatial skill compared to olanzapine. CONCLUSION: The meta-analysis was able
      to detect some trends in the data analyzed, but did not show any drug having a
      uniform positive cognitive profile.

PMID- 25597384
TI  - C-terminal hybrid mutant of Bacillus pumilus cyanide dihydratase dramatically
      enhances thermal stability and pH tolerance by reinforcing oligomerization.
AB  - AIMS: To investigate the impact of the highly variable C-terminal domain of
      cyanide dihydratase, a member of the nitrilase superfamily, on its activity and
      stability. METHODS AND RESULTS: Generating and analysing the thermal stability
      and pH tolerance of chimeric cyanide dihydratase proteins has provided a platform
      to investigate domains within the C-terminus and their effect on quaternary
      structure of the protein. The protein oligomerization state was inferred from
      native protein size by gel exclusion chromatography. CONCLUSIONS: Our data
      indicates that the influence of the cyanide dihydratase C-terminus on thermal
      stability stems from its participation in oligomerization at the major C-surface
      interface. The formation of this surface is crucial for the activity and
      stability of CynD. Gel filtration chromatography of an N-terminal deletion
      mutant, CynDpum ?303, revealed a defect in oligomerization, and another mutant
      R67C was suppressed by introduction of a heterologous C-terminus as a chimeric
      protein. This indicates that the C-terminus from Pseudomonas stutzeri stabilizes
      CynD by supporting oligomerization between dimers at the C-surface. The chimeric
      protein CynDpum-stut exhibited full activity at pH 9, a pH where the parent
      enzyme is nearly inactive, and retained 40% of its activity at pH 9.5 making it a
      unique pH tolerant mutant. SIGNIFICANCE AND IMPACT OF THE STUDY: The study
      characterized a chimeric protein with remarkable thermal stability and tolerance
      to alkaline conditions, features essential for practical application as
      industrial cyanide solutions are maintained as highly alkaline solutions to
      prevent formation of hydrogen cyanide gas.

PMID- 25597385
TI  - Teneligliptin : expectations for its pleiotropic action.
AB  - INTRODUCTION: The main aim in the management of diabetes mellitus is to prevent
      the development of its complications. Large fluctuations in glucose levels may
      increase the risk of complications, so improved control of glucose fluctuations,
      in addition to management of chronic hyperglycemia, could represent an important
      goal in diabetes pharmacotherapy. AREAS COVERED: Pre-clinical and clinical
      studies suggest that poor control of blood glucose fluctuations contributes to
      progression of diabetic vascular complications. Dipeptidyl peptidase (DPP)-4
      inhibitors are one of several drug classes used to manage diabetes, and the
      potential vasoprotective effects of DPP-4 inhibition have attracted attention in
      recent years. The DPP-4 inhibitor teneligliptin was approved in Japan in 2012 and
      in Korea in 2014. Teneligliptin differs in its structural and pharmacokinetic
      characteristics compared with other drugs in the same class. It appears to have
      potent, sustained effects on glycemic control, thereby reducing the complications
      of hypoglycemia and postprandial hyperglycemia. Because of its effects on
      vascular function, teneligliptin may be beneficial in patients at high risk of
      cardiovascular disease. EXPERT OPINION: The possible pleiotropic effects of
      teneligliptin, such as those on endothelial function and metabolic syndrome, are
      of great interest. This review examines these effects and their potential
      clinical relevance.

PMID- 25597386
TI  - Aclidinium bromide plus formoterol for the treatment of chronic obstructive
      pulmonary disease.
AB  - INTRODUCTION: Drugs that target dynamic hyperinflation such as long-acting beta-2
      agonists and long-acting antimuscarinic antagonists form a cornerstone of chronic
      obstructive pulmonary disease (COPD) management. The idea of combining these two
      medications in a single formulation, which may potentially improve patient
      compliance, is novel and attractive. AREAS COVERED: The pharmacologic profiles of
      aclidinium bromide and formoterol fumarate are discussed. However, studies to
      define drug interactions and alterations in the pharmacodynamics and
      pharmacokinetics of the fixed dose combination (FDC) of aclidinium
      bromide/formoterol fumarate in large populations remain unpublished. Results of
      Phase II and two Phase III pivotal trials, ACLIFORM/COPD and AUGMENT COPD,
      evaluating the FDC are discussed. EXPERT OPINION: Initial data for the
      aclidinium/formoterol inhaler appears to be promising for impacting the lung
      function. To define if this benefit translates into improved long-term outcomes
      of decreased exacerbation frequency, improved quality of life and decreased
      disease-specific mortality are important. The introduction of this combination
      will likely have a significant impact on the prescribing habits of physicians
      across the world.

PMID- 25597387
TI  - LCZ696 : a new paradigm for the treatment of heart failure?
AB  - INTRODUCTION: Heart failure (HF) represents a significant healthcare issue
      because of its ever-increasing prevalence, poor prognosis and complex
      pathophysiology. Currently, blockade of the renin-angiotensin-aldosterone system
      (RAAS) is the cornerstone of treatment; however, the combination of RAAS blockade
      with inhibition of neprilysin (NEP), an enzyme that degrades natriuretic
      peptides, has recently emerged as a potentially superior treatment strategy.
      AREAS COVERED: Following the results of the recent Phase III Prospective
      Comparison of ARNI with ACEI to Determine Impact on Global Mortality and
      Morbidity in Heart Failure clinical trial in patients with chronic HF with
      reduced ejection fraction (HF-REF), this review focuses on LCZ696 , a first-in
      class angiotensin receptor NEP inhibitor. This drug consists of a supramolecular
      complex containing the angiotensin receptor inhibitor valsartan in combination
      with the NEP inhibitor prodrug, AHU377. Following oral administration, the LCZ696
      complex dissociates and the NEP inhibitor component is metabolized to the active
      form (LBQ657). Aspects of the trial that might be relevant to clinical practice
      are also discussed. EXPERT OPINION: Speculation that LCZ696 will pass the
      scrutiny of regulatory agencies for HF-REF appears to be justified, and it is
      likely to become a core therapeutic component in the near future. Replication of
      the eligibility criteria and titration protocol used in the PARADIGM-HF trial
      would be valuable in clinical practice and may minimize the risk of adverse
      events. Although long-term data remain to be generated, the promising results
      regarding hypertension are likely to expedite acceptance of the drug for HF-REF.

PMID- 25597389
TI  - How accelerated Golgi trafficking may drive Alzheimer's disease (comment on DOI
      10.1002/bies.201400116) .

PMID- 25597390
TI  - Attenuated phagocytosis of secondary necrotic neutrophils by macrophages in aged
      and SMP30 knockout mice.
AB  - AIM: Secondary necrotic cells generated in vivo induce inflammatory responses;
      for example, the production of macrophage inflammatory protein-2 (MIP-2) and
      subsequent infiltration of neutrophils. The aim of the present study was to
      elucidate the effect of aging on the phagocytosis of secondary necrotic cells and
      the inflammatory responses by using either wild-type (WT) young mice, WT aged
      mice or senescence-accelerated mice (SMP30(-/-) mice). METHODS: The phagocytosis
      of secondary necrotic neutrophils with resident macrophage from either WT young
      mice, WT aged mice or SMP30(-/-) mice was examined by coculturing macrophages
      with secondary necrotic neutrophils in vitro. To investigate the inflammatory
      response induced by secondary necrotic cells, time-dependent infiltration of
      neutrophils and production of MIP-2 were determined in the peritoneal cavity on
      the injection of secondary necrotic cells. RESULTS: The phagocytosis of secondary
      necrotic cells by macrophages from WT aged and SMP30(-/-) mice was significantly
      reduced as compared with that by macrophages from WT young mice. On peritoneal
      injection of secondary necrotic cells, the peak time of neutrophil infiltration
      was earlier in SMP30(-/-) mice than in WT young mice. The number of neutrophils
      in SMP30(-/-) mice at the peak time was also greater than that in WT young mice.
      CONCLUSIONS: Our findings showed that the phagocytosis of secondary necrotic
      cells was attenuated in aged mice and SMP30(-/-) mice, and that the MIP-2
      production was enhanced and subsequently neutrophil infiltration was exaggerated
      on peritoneal injection of secondary necrotic cells into those mice.

PMID- 25597391
TI  - Replication of a cognitive behavioral therapy for chronic pain group protocol by
      therapists in training.
AB  - According to the American Psychological Association (Division 12), there is
      strong, long-standing research support for cognitive behavioral therapy (CBT) to
      treat chronic pain. Furthermore, meta-analytic comparisons have shown CBT to be
      highly efficacious. However, not all researchers agree with this conclusion. The
      purpose of the current pilot study was to determine whether a CBT outpatient,
      group-based treatment facilitated by junior therapists benefited veterans who
      suffer from mixed idiopathic, chronic, noncancer pain, thus replicating results
      from effective CBT programs from the past. A sample of 46 veterans aged 33 to 81
      years with chronic, noncancer pain who participated in an outpatient CBT pain
      group therapy protocol at a Midwestern Veterans Affairs Medical Center between
      November 3, 2009, and September 2, 2010 was evaluated. All participants completed
      a pre- and postintervention assessment. Paired-samples t tests were conducted to
      evaluate the impact of the program on veterans' scores on assessment measures. No
      significant difference was found between the pre- and posttest primary outcome
      measures of pain intensity. A significant difference was established between the
      pre- and posttest secondary outcome measure of catastrophizing. However, there
      were no other significant differences found among the remaining pre- and posttest
      secondary outcome measures of pain interference, disability, and psychological
      distress. Training junior therapists on how to use CBT protocols may be enhanced
      by paying greater attention to what mechanisms are responsible for the desired
      outcomes among veterans with chronic pain.

PMID- 25597393
TI  - Use of model for end-stage liver disease exceptions for donation after cardiac
      death graft recipients relisted for liver transplantation.
AB  - Donation after cardiac death (DCD) liver transplantation is associated with
      increased biliary complications and graft failure. Yet for unclear reasons, DCD
      recipients relisted for transplantation have lower wait-list mortality than other
      retransplant candidates. We used Organ Procurement and Transplantation Network
      and United Network for Organ Sharing data from 2002 to 2011 to evaluate all DCD
      recipients relisted for transplantation to evaluate the impact of the utilization
      of Model for End-Stage Liver Disease (MELD) exception points on wait-list
      outcomes. Of 262 DCD recipients relisted for liver transplantation >2 weeks after
      initial transplantation, 82 (31.3%) applied for a nonstandardized MELD exception,
      and 68 (82.9%) had >=1 exception approved. Of the relisted DCD recipients, 187
      (71.4%) underwent retransplantation; among those with an approved MELD exception,
      85.2% underwent retransplantation versus 57.1% of those with an exception denied
      and 69.4% of those not applying for an exception (P=0.02). In contrast, those
      receiving MELD exception points were significantly less likely to be removed from
      the wait list for death or clinical deterioration in comparison with those not
      applying for an exception (7.1% versus 19.4%, P=0.02). In multivariate models,
      patients with an approved exception were 3.3 times more likely to undergo
      retransplantation than those not applying for an exception. Standardized criteria
      for exception points among DCD recipients should be established to ensure uniform
      access to retransplantation.

PMID- 25597392
TI  - Development of potent inhibitors of pyocyanin production in Pseudomonas
      aeruginosa.
AB  - The development of new approaches for the treatment of antimicrobial-resistant
      infections is an urgent public health priority. The Pseudomonas aeruginosa
      pathogen, in particular, is a leading source of infection in hospital settings,
      with few available treatment options. In the context of an effort to develop
      antivirulence strategies to combat bacterial infection, we identified a series of
      highly effective small molecules that inhibit the production of pyocyanin, a
      redox-active virulence factor produced by P. aeruginosa. Interestingly, these new
      antagonists appear to suppress P. aeruginosa virulence factor production through
      a pathway that is independent of LasR and RhlR. 

PMID- 25597394
TI  - Lipophilic tetranuclear ruthenium(II) complexes as two-photon luminescent
      tracking non-viral gene vectors.
AB  - Fluorescence detection is the most effective tool for tracking gene delivery in
      living cells. To reduce photodamage and autofluorescence and to increase deep
      penetration into cells, choosing appropriate fluorophores that are capable of two
      photon activation under irradiation in the NIR or IR regions is an effective
      approach. In this work, we have developed six tetranuclear ruthenium(II)
      complexes, GV1-6, and have studied their one- and two-photon luminescence
      properties. DNA interaction studies have demonstrated that GV2-6, bearing
      hydrophobic alkyl ether chains, show more efficient DNA condensing ability but
      lower DNA binding constants than GV1. However, the hydrophobic alkyl ether chains
      also enhance the DNA delivery ability of GV2-6 compared with that of GV1. More
      importantly, we have applied GV1-6 as non-viral gene vectors for tracking DNA
      delivery in living cells by one- and two-photon fluorescence microscopies. In two
      photon microscopy, a high signal-to-noise contrast was achieved by irradiation
      with an 830 nm laser. This is the first example of the use of transition-metal
      complexes for two-photon luminescent tracking of the cellular pathways of gene
      delivery and as DNA carriers. Our work provides new insights into improving real
      time tracking during gene delivery and transfection as well as important
      information for the design of multifunctional non-viral vectors. 

PMID- 25597395
TI  - Minimum standards for continence care in the UK.
AB  - AIM: This paper reports on the publication of a joint statement on minimum
      standards for continence care in the UK. METHODS: A multidisciplinary working
      party were tasked with creating standards for both training and education in
      continence care, as well as explicit standards for a framework of service
      delivery. This was done through a process of extensive consultation with relevant
      professional bodies. RESULTS: The standards suggest a modular structure to
      continence training, including basic, male, female, catheter care etc.
      Discussions on service provision cover primary care through to expert tertiary
      centres. CONCLUSIONS: This is the first attempt to standardise continence care
      and training for all health care professionals nationally. The document is
      available on the United Kingdom Continence Society website www.ukcs.uk.net.

PMID- 25597397
TI  - Sexual dimorphism and phenotypic plasticity in the antennal lobe of a stingless
      bee, Melipona scutellaris.
AB  - Among social insects, the stingless bees (Apidae, Meliponini), a mainly tropical
      group of highly eusocial bees, present an intriguing variety of well-described
      olfactory-dependent behaviors showing both caste- and sex-specific adaptations.
      By contrast, little is known about the neural structures underlying such
      behavioral richness or the olfactory detection and processing abilities of this
      insect group. This study therefore aimed to provide the first detailed
      description and comparison of the brains and primary olfactory centers, the
      antennal lobes, of the different members of a colony of the stingless bee
      Melipona scutellaris. Global neutral red staining, confocal laser scanning
      microscopy, and 3D reconstructions were used to compare the brain structures of
      males, workers, and virgin queens with a special emphasis on the antennal lobe.
      We found significant differences between both sexes and castes with regard to the
      relative volumes of olfactory and visual neuropils in the brain and also in the
      number and volume of the olfactory glomeruli. In addition, we identified one
      (workers, queens) and three or four (males) macroglomeruli in the antennal lobe.
      In both sexes and all castes, the largest glomerulus (G1) was located at a
      similar position relative to four identified landmark glomeruli, close to the
      entrance of the antennal nerve. This similarity in position suggests that G1s of
      workers, virgin queens, and males of M. scutellaris may correspond to the same
      glomerular entity, possibly tuned to queen-emitted volatiles since all colony
      members need this information.

PMID- 25597399
TI  - A narrow window of cortical tension guides asymmetric spindle positioning in the
      mouse oocyte.
AB  - Cell mechanics control the outcome of cell division. In mitosis, external forces
      applied on a stiff cortex direct spindle orientation and morphogenesis. During
      oocyte meiosis on the contrary, spindle positioning depends on cortex softening.
      How changes in cortical organization induce cortex softening has not yet been
      addressed. Furthermore, the range of tension that allows spindle migration
      remains unknown. Here, using artificial manipulation of mouse oocyte cortex as
      well as theoretical modelling, we show that cortical tension has to be tightly
      regulated to allow off-center spindle positioning: a too low or too high cortical
      tension both lead to unsuccessful spindle migration. We demonstrate that the
      decrease in cortical tension required for spindle positioning is fine-tuned by a
      branched F-actin network that triggers the delocalization of myosin-II from the
      cortex, which sheds new light on the interplay between actin network architecture
      and cortex tension. 

PMID- 25597398
TI  - Structure of the sulfoxide synthase EgtB from the ergothioneine biosynthetic
      pathway.
AB  - The non-heme iron enzyme EgtB catalyzes O2 -dependent C-S bond formation between
      gamma-glutamyl cysteine and N-alpha-trimethyl histidine as the central step in
      ergothioneine biosynthesis. Both, the catalytic activity and the architecture of
      EgtB are distinct from known sulfur transferases or thiol dioxygenases. The
      crystal structure of EgtB from Mycobacterium thermoresistibile in complex with
      gamma-glutamyl cysteine and N-alpha-trimethyl histidine reveals that the two
      substrates and three histidine residues serve as ligands in an octahedral iron
      binding site. This active site geometry is consistent with a catalytic mechanism
      in which C-S bond formation is initiated by an iron(III)-complexed thiyl radical
      attacking the imidazole ring of N-alpha-trimethyl histidine.

PMID- 25597396
TI  - Differential remodeling of extracellular matrices by breast cancer initiating
      cells.
AB  - Cancer initiating cells (CICs) have been the focus of recent anti-cancer
      therapies, exhibiting strong invasion capability via potentially enhanced ability
      to remodel extracellular matrices (ECM). We have identified CICs in a human
      breast cancer cell line, MX-1, and developed a xenograft model in SCID mice. We
      investigated the CICs' matrix-remodeling effects using Second Harmonic Generation
      (SHG) microscopy to identify potential phenotypic signatures of the CIC-rich
      tumors. The isolated CICs exhibit higher proliferation, drug efflux and drug
      resistant properties in vitro; were more tumorigenic than non-CICs, resulting in
      more and larger tumors in the xenograft model. The CIC-rich tumors have less
      collagen in the tumor interior than in the CIC-poor tumors supporting the idea
      that the CICs can remodel the collagen more effectively. The collagen fibers were
      preferentially aligned perpendicular to the CIC-rich tumor boundary while
      parallel to the CIC-poor tumor boundary suggesting more invasive behavior of the
      CIC-rich tumors. These findings would provide potential translational values in
      quantifying and monitoring CIC-rich tumors in future anti-cancer therapies. CIC
      rich tumors remodel the collagen matrix more than CIC-poor tumors. 

PMID- 25597400
TI  - Assessment of oxygenation and comorbidities improves outcome prediction in
      patients with community-acquired pneumonia with a low CRB-65 score.
AB  - BACKGROUND: Addition of assessment of comorbid diseases ('D') and oxygen
      saturation ('S') to the CRB-65 score has been recommended to improve its accuracy
      for risk stratification in community-acquired pneumonia (CAP). The aim of this
      study was to validate the resulting DS-CRB-65 score in a large cohort of patients
      with CAP. METHODS: A total of 4432 patients prospectively enrolled in the CAPNETZ
      cohort were included in this study. Predefined end points were 28-day mortality,
      requirement for mechanical ventilation or vasopressors (MV/VS) and requirement
      for MV/VS or intensive care unit admission (MV/VS/ICU). Receiver operating
      characteristic curve analysis was used to determine the accuracy of the CRB-65
      score and the addition of D (extra-pulmonary comorbidities) and S (oxygen
      saturation <90% or partial pressure of oxygen <8 kPa). Binary logistic regression
      and the method of Hanley and McNeil were used to compare the criteria. RESULTS:
      The mortality rate was 4.0%, and 4.2% of patients required MV/VS and 6.6%
      required MV/VS/ICU. After multivariate analysis, D and S independently were added
      to the CRB-65 criteria for mortality prediction, but only S improved prediction
      of MV/VS and MV/VS/ICU (P < 0.001 for all). The area under the curve of the CRB
      65 score was significantly improved by adding D and S for all end points (P <
      0.02). Amongst patients who died or required MV/VS despite a CRB-65 score of 0,
      64-80% would have been identified by the DS-CRB-65 score. CONCLUSIONS: The
      addition of assessment of oxygenation and comorbidities significantly improved
      the prognostic accuracy of the CRB-65 score. Consequently, the DS-CRB-65 score
      may have a useful role in risk stratification algorithms for CAP.

PMID- 25597402
TI  - Dendritic heterojunction nanowire arrays for high-performance supercapacitors.
AB  - Herein, we designed and synthesized for the first time a series of 3D dendritic
      heterojunction arrays on Ni foam substrates, with NiCo2S4 nanowires as cores and
      NiCo2O4, NiO, Co3O4, and MnO2 nanowires as branches, and studied systematically
      their electrochemical performance in comparison with their counterparts in
      core/shell structure. Attributed to the following reasons: (1) both core and
      branch are pseudocapacitively active materials, (2) the special dendritic
      structure with considerable inter-nanowire space enables easy access of
      electrolyte to the core and branch surfaces, and (3) the highly conductive
      NiCo2S4 nanowire cores provide "superhighways" for charge transition, NiCo2S4
      cored dendritic heterojunction electrodes synergistically lead to ultrahigh
      specific capacitance, good rate capability, and excellent cycling life. These
      results of core/branch dentritic heterojunction arrays is universially superior
      to their core/shell conterparts, thus this is a significant improvement of
      overall electrochemical performance. 

PMID- 25597403
TI  - Is HIV post-exposure prophylaxis required following occupational exposure to a
      source patient who is virologically suppressed on antiretroviral therapy?

PMID- 25597401
TI  - Astrocytes increase ATP exocytosis mediated calcium signaling in response to
      microgroove structures.
AB  - Following central nervous system (CNS) injury, activated astrocytes form glial
      scars, which inhibit axonal regeneration, leading to long-term functional
      deficits. Engineered nanoscale scaffolds guide cell growth and enhance
      regeneration within models of spinal cord injury. However, the effects of micro
      /nanosize scaffolds on astrocyte function are not well characterized. In this
      study, a high throughput (HTP) microscale platform was developed to study
      astrocyte cell behavior on micropatterned surfaces containing 1 MUm spacing
      grooves with a depth of 250 or 500 nm. Significant changes in cell and nuclear
      elongation and alignment on patterned surfaces were observed, compared to on flat
      surfaces. The cytoskeleton components (particularly actin filaments and focal
      adhesions) and nucleus-centrosome axis were aligned along the grooved direction
      as well. More interestingly, astrocytes on micropatterned surfaces showed
      enhanced mitochondrial activity with lysosomes localized at the lamellipodia of
      the cells, accompanied by enhanced adenosine triphosphate (ATP) release and
      calcium activities. These data indicate that the lysosome-mediated ATP exocytosis
      and calcium signaling may play an important role in astrocytic responses to
      substrate topology. These new findings have furthered our understanding of the
      biomechanical regulation of astrocyte cell-substrate interactions, and may
      benefit the optimization of scaffold design for CNS healing.

PMID- 25597404
TI  - Previous breastfeeding experience and duration of any and exclusive breastfeeding
      among multiparous mothers.
AB  - BACKGROUND: High breastfeeding attrition rates have been attributed to a number
      of factors, but the effect of previous breastfeeding experience on subsequent
      breastfeeding duration has not been adequately investigated. METHODS: In this
      study, 559 multiparous mothers were recruited and followed prospectively for 12
      months or until the infant was weaned. RESULTS: When compared with having
      previously breastfed for > 3 months, no previous breastfeeding experience (HR
      3.24 [95% CI 2.37-4.42]) or a breastfeeding duration of <= 3 months (HR 2.56; 95%
      CI 2.05?3.20) substantially increased the risk of early weaning. Similarly,
      participants who had not exclusively breastfed (HR 1.82 [95% CI 1.46?2.26]) or
      who had exclusively breastfed for <= 2 months (HR 1.65 [95% CI 1.29?2.10]) were
      more likely to stop exclusive breastfeeding when compared with those who had
      exclusively breastfed for > 2 months. More than 40 percent of the participants
      who had previously breastfed for > 3 months had shorter current breastfeeding
      durations. The median decreases in any and exclusive breastfeeding for this group
      were 16.4 weeks and 13.1 weeks, respectively. CONCLUSIONS: Multiparous women with
      no previous breastfeeding experience and those with a short duration of previous
      breastfeeding should be provided with greater support to promote a longer
      duration of breastfeeding. Multiparous women with a longer duration of
      breastfeeding should be strongly encouraged to meet or exceed this duration with
      their current infant.

PMID- 25597405
TI  - Germline & somatic mosaicism: the 2014 annual scientific meeting of the Human
      Genome Variation Society.

PMID- 25597406
TI  - Influence of sexual competition and social context on homosexual behavior in
      adolescent female Japanese macaques.
AB  - We explored the role that sexual and social partners play in the expression of
      female homosexual behavior among adolescent female Japanese macaques at
      Arashiyama, Japan. Our data fully or partially supported all the predictions
      related to four non-mutually exclusive hypotheses, namely the "adult male
      disinterest in adolescent females" hypothesis, the "numerous homosexual adult
      females" hypothesis, the "safer homosexual interactions" hypothesis and the "same
      sex sexual interactions" hypothesis. Our results show that both sexual context
      (e.g., lack of adolescent female attractivity toward adult males, presence of
      motivated same-sex sexual partners), and social context (e.g., risk of
      aggression) help explain the high frequency and prevalence of homosexual behavior
      in adolescent females in the Arashiyama group of Japanese macaques. As with adult
      females, whose homosexual consortships do not reflect generalized patterns of
      social affiliation or kinship, we found that adolescent females' same-sex sexual
      partners were neither kin, nor were they non-kin individuals with whom adolescent
      females were closely affiliated outside of a consortship context. Our study
      furthers the growing database of female homosexual behavior in Japanese macaques
      and provides additional evidence that homosexual behavior as expressed by
      adolescent female Japanese macaques is, like heterosexual behavior, sexual in
      nature. We discuss the relevance of our findings to a broader comparative
      approach that may shed light upon the development and evolution of human
      homosexuality.

PMID- 25597407
TI  - Experimental and theoretical investigation of macro-periodic and micro-random
      nanostructures with simultaneously spatial translational symmetry and long-range
      order breaking.
AB  - Photonic and plasmonic quasicrystals, comprising well-designed and regularly
      arranged patterns but lacking spatial translational symmetry, show sharp
      diffraction patterns resulting from their long-range order in spatial domain.
      Here we demonstrate that plasmonic structure, which is macroscopically arranged
      with spatial periodicity and microscopically constructed by random metal
      nanostructures, can also exhibit the diffraction effect experimentally, despite
      both of the translational symmetry and long-range order are broken in spatial
      domain simultaneously. With strategically pre-formed metal nano-seeds, the
      tunable macroscopically periodic (macro-periodic) pattern composed from
      microscopically random (micro-random) nanoplate-based silver structures are
      fabricated chemically through photon driven growth using simple light source with
      low photon energy and low optical power density. The geometry of the micro
      structure can be further modified through simple thermal annealing. While the
      random metal nanostructures suppress high-order Floquet spectra of the spatial
      distribution of refractive indices, the maintained low-order Floquet spectra
      after the ensemble averaging are responsible for the observed diffraction effect.
      A theoretical approach has also been established to describe and understand the
      macro-periodic and micro-random structures with different micro-geometries. The
      easy fabrication and comprehensive understanding of this metal structure will be
      beneficial for its application in plasmonics, photonics and optoelectronics. 

PMID- 25597408
TI  - Integrative genomics identifies YY1AP1 as an oncogenic driver in EpCAM(+) AFP(+)
      hepatocellular carcinoma.
AB  - Identification of key drivers and new therapeutic targets is important given the
      poor prognosis for hepatocellular carcinoma (HCC) patients, particularly those
      ineligible for surgical resection or liver transplant. However, the approach to
      identify such driver genes is facing significant challenges due to the
      genomically heterogenous nature of HCC. Here we tested whether the integrative
      genomic profiling of a well-defined HCC subset that is classified by an extreme
      EpCAM(+) AFP(+) gene expression signature and associated with poor prognosis, all
      attributes of a stem cell-like phenotype, could uncover survival-related driver
      genes in HCC. Following transcriptomic analysis of the well-defined HCC cases, a
      Gene Set Enrichment Analysis coupled with genomic copy number alteration
      assessment revealed that YY1-associated protein 1 (YY1AP1) is a critical
      oncoprotein specifically activated in EpCAM(+) AFP(+) HCC. YY1AP1 silencing
      eliminates oncogene addiction by altering the chromatin landscape and triggering
      massive apoptosis in vitro and tumor suppression in vivo. YY1AP1 expression
      promotes HCC proliferation and is required for the maintenance of stem cell
      features. We revealed that YY1AP1 cooperates with YY1 to alter the chromatin
      landscape and activate transcription of stemness regulators. Thus YY1AP1 may
      serve as a key molecular target for EpCAM(+) AFP(+) HCC subtype. Our results
      demonstrate the feasibility and power of a new strategy by utilizing well-defined
      patient samples and integrative genomics to uncover critical pathways linked to
      HCC subtypes with prognostic impact. 

PMID- 25597409
TI  - Signaling switch of the urotensin II vasosactive peptide GPCR: prototypic
      chemotaxic mechanism in glioma.
AB  - Multiform glioblastomas (GBM) are the most frequent and aggressive primary brain
      tumors in adults. The poor prognosis is due to neo-angiogenesis and cellular
      invasion, processes that require complex chemotaxic mechanisms involving
      motility, migration and adhesion. Understanding these different cellular events
      implies identifying receptors and transduction pathways that lead to and promote
      either migration or adhesion. Here we establish that glioma express the
      vasoactive peptide urotensin II (UII) and its receptor UT and that UT-mediated
      signaling cascades are involved in glioma cell migration and adhesion. Components
      of the urotensinergic systems, UII and UT, are widely expressed in patient
      derived GBM tissue sections, glioma cell lines and fresh biopsy explants.
      Interestingly, gradient concentrations of UII produced chemoattracting
      migratory/motility effects in glioma as well as HEK293 cells expressing human UT.
      These effects mainly involved the G13/Rho/rho kinase pathway while partially
      requiring Gi/o/PI3K components. In contrast, we observed that homogeneous
      concentrations of UII drastically blocked cell motility and stimulated cell
      matrix adhesions through a UT/Gi/o signaling cascade, partially involving
      phosphatidylinositol-3 kinase. Finally, we provide evidence that, in glioma
      cells, homogeneous concentration of UII allowed translocation of Galpha13 to the
      UT receptor at the plasma membrane and increased actin stress fibers,
      lamellipodia formation and vinculin-stained focal adhesions. UII also provoked a
      re-localization of UT precoupled to Galphai in filipodia and initiated integrin
      stained focal points. Altogether, these findings suggest that UT behaves as a
      chemotaxic receptor, relaying a signaling switch between directional migration
      and cell adhesion under gradient or homogeneous concentrations, thereby
      redefining sequential mechanisms affecting tumor cells during glioma invasion.
      Taken together, our results allow us to propose a model in order to improve the
      design of compounds that demonstrate signaling bias for therapies that target
      specifically the Gi/o signaling pathway. 

PMID- 25597411
TI  - Effectiveness of lifestyle change plus dental care program in improving glycemic
      and periodontal status in aging patients with diabetes: a cluster, randomized,
      controlled trial.
AB  - BACKGROUND: Currently, there is an increased prevalence of diabetes mellitus
      among the aging adult population. To minimize adverse effects on glycemic
      control, prevention and management of general and oral complications in patients
      with diabetes are essential. The objective of this study is to assess the
      effectiveness of the lifestyle change plus dental care (LCDC) program to improve
      glycemic and periodontal status in aging patients with diabetes. METHODS: A
      cluster, randomized, controlled trial was conducted in Health Centers 54
      (intervention) and 59 (control) from October 2013 to April 2014. Sixty-six
      patients with diabetes per health center were included. At baseline, the
      intervention group attended 20-minute lifestyle and oral health education,
      individual lifestyle counseling, application of a self-regulation manual, and
      individual oral hygiene instruction. At month 3, the intervention group received
      individual lifestyle counseling and oral hygiene instruction. The intervention
      group received booster education every visit by viewing a 15-minute educational
      video. The control group received a routine program. Participants were assessed
      at baseline and 3- and 6-month follow-up for glycemic and periodontal status.
      Data were analyzed by using descriptive statistic, chi(2) test, Fisher exact
      test, t test, and repeated-measures analysis of variance. RESULTS: After the 6
      month follow-up, participants in the intervention group had significantly lower
      glycated hemoglobin, fasting plasma glucose, plaque index, gingival index,
      probing depth, and attachment loss when compared with the control group.
      CONCLUSION: The combination of lifestyle change and dental care in one program
      improved both glycemic and periodontal status in older patients with diabetes.

PMID- 25597410
TI  - Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell
      growth, migration and invasion via direct targeting Akt1.
AB  - Although increasing evidence indicated that the deregulation of microRNAs
      (miRNAs) contributes to tumorigenesis and invasion, little is known about the
      role of miR-637 in human gliomas. In the present study, we found that the
      expression level of miR-637 was significantly reduced in clinical glioma tissues
      compared with normal brain tissues. Moreover, we revealed that the introduction
      of miR-637 dramatically suppressed glioma cell growth, migration and invasion in
      vitro and in vivo. Further studies revealed that Akt1 is a direct target gene of
      miR-637. Silencing of Akt1 inhibited the growth and invasion of glioma cells by
      decreasing phosphorylated Akt, beta-catenin, phosphorylated Foxo1 and Cyclin D1
      and inducing the expression of Foxo1, which was consistent with the effect of miR
      637 overexpression. Suppressed expression of miR-637 and increased Akt1 protein
      levels were correlated with unfavorable progression and poor prognosis,
      respectively, and a negative relationship between the miR-637 expression and Akt1
      protein levels was observed in gliomas. Our findings provide new insights into
      the role of miR-637 in the development of gliomas, and implicate the potential
      application of miR-637 in cancer therapy.

PMID- 25597413
TI  - Koebner phenomenon in a patient with lichen sclerosus following a jellyfish
      sting: an exceptional morphology.

PMID- 25597412
TI  - The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in
      chemoresistant non-small-cell lung cancer.
AB  - Programmed cell death ligand-1 (PD-L1) has recently gained considerable attention
      for its role in tumor immune escape. Here, we identify a miR-197/CKS1B/STAT3
      mediated PD-L1 network in chemoresistant non-small-cell lung cancer (NSCLC),
      independent of immunoinhibitory signals. miR-197 is downregulated in platinum
      resistant NSCLC specimens, resulting in the promotion of chemoresistance,
      tumorigenicity, and pulmonary metastasis in vitro and in vivo. Mechanistic
      investigations reveal that a miR-197-mediated CKS1B/STAT3 axis exerts tumor
      progression regulated by various oncogenic genes (Bcl-2, c-Myc, and cyclin D1),
      and PD-L1 is a putative biomarker of this axis. Furthermore, we demonstrate that
      a miR-197 mimic sensitizes PD-L1(high) drug-resistant cells to chemotherapy.
      These results indicate that the biological interaction between PD-L1 and
      chemoresistance occurs through the microRNA regulatory cascade. More importantly,
      expression levels of miR-197 are inversely correlated with PD-L1 expression (n =
      177; P = 0.026) and are associated with worse overall survival (P = 0.015). Our
      discoveries suggest that the miR-197/CKS1B/STAT3-mediated network can drive tumor
      PD-L1 expression as a biomarker of this cascade, and miR-197 replacement therapy
      may be a potential treatment strategy for chemoresistant NSCLC. 

PMID- 25597414
TI  - Acne in women.
AB  - This review focuses on the subject of acne in women, a disease that is
      increasingly common and that can also affect men. Adult acne differs from the
      type of acne that occurs in teenagers, and it may persist beyond adolescence or
      have its onset at an older age (adult-onset acne or late acne). Acne can have a
      negative impact on the quality of life of patients at any age, leading to a
      negative body image and decrease in self-esteem, and in older patients it can
      result in discrimination in the workplace and in other social environments. Acne
      in women must be understood as a specific problem, and here we discuss the
      pathogenesis, clinical presentation, psychology and treatment of this very
      prevalent problem. 

PMID- 25597415
TI  - Impact of lipid-based nutrient supplementation (LNS) on children's diet adequacy
      in Western Uganda.
AB  - Lipid-based nutrient supplements (LNS) can help treat undernutrition; however,
      the dietary adequacy of children supplemented with LNS, and household utilisation
      patterns are not well understood. We assessed diet adequacy and the quality of
      complementary foods by conducting a diet assessment of 128 Ugandan children, ages
      6-59 months, who participated in a 10-week programme for children with moderate
      acute malnutrition (MAM, defined as weight-for-age z-score < -2). Caregivers were
      given a weekly ration of 650 kcal day(-1) (126 g day(-1) ) of a peanut/soy LNS.
      Two 24-h dietary recalls were administered per child. LNS was offered to 86% of
      targeted children at least once. Among non-breastfed children, over 90% met their
      estimated average requirement (EAR) cut-points for all examined nutrients. Over
      90% of breastfed children met EAR cut-points for nutrient density for most
      nutrients, except for zinc where 11.7% met cut-points. A lower proportion of both
      breastfed and non-breastfed children met adjusted EARs for the specific
      nutritional needs of MAM. Fewer than 20% of breastfed children met EAR nutrient
      density guidelines for MAM for zinc, vitamin C, vitamin A and folate. Underweight
      status, the presence of a father in the child's home, and higher programme
      attendance were all associated with greater odds of feeding LNS to targeted
      children. Children in this community-based supplemental feeding programme who
      received a locally produced LNS exhibited substantial micronutrient deficiencies
      given the special dietary needs of this population. These results can help inform
      programme strategies to improve LNS targeting, and highlight potential nutrient
      inadequacies for consumers of LNS in community-based settings.

PMID- 25597416
TI  - Deciphering metabolic abnormalities associated with Alzheimer's disease in the
      APP/PS1 mouse model using integrated metabolomic approaches.
AB  - The transgenic mouse APP/PS1 is widely employed by neuroscientists because
      reproduces well some of the neuropathological and cognitive deficits observed in
      human Alzheimer's disease. In this study, serum samples from APP/PS1 mice (n =
      30) and wild-type controls (n = 30) were analyzed using a metabolomic
      multiplatform based on the combination of gas chromatography-mass spectrometry
      and ultra-high performance liquid chromatography-mass spectrometry, in order to
      obtain wide information about serum metabolome. Metabolic profiles showed
      significant differences between the groups of study, and numerous metabolites
      were identified as potential players in the development of Alzheimer-type
      disorders in this transgenic model. Pathway analysis revealed the involvement of
      multiple metabolic networks in the underlying pathology, such as deficiencies in
      energy metabolism, altered amino acid homeostasis, abnormal membrane lipid
      metabolism, and other impairments related to the integrity of the central nervous
      system. It is noteworthy that some of these metabolomic markers are in accordance
      with pathological alterations observed in human Alzheimer's disease, while others
      have not been previously described. Therefore, these results demonstrate the
      potential of metabolomics and the use of transgenic animal models to understand
      the pathogenesis of Alzheimer's disease. 

PMID- 25597417
TI  - Mapping of alkali-sensing sites of the insulin receptor-related receptor. The
      role of L2 and fibronectin domains.
AB  - Insulin receptor-related receptor (IRR) is a member of the insulin receptor (IR)
      family that works as an extracellular alkali sensor with positive cooperativity.
      The pH sensing property of IRR is defined by its extracellular region and
      involves multiple domains. We have previously demonstrated the primary role of
      L1C domains and identified potentially important amino acid residues within these
      domains. In this study, we addressed the roles of L2 and FnIII domains. Within
      the L2 domain, five amino acid residues (M406, V407, D408, P436 and V437) were
      identified as IRR-specific by performing a species conservation analysis of the
      IR family. Single-point mutations of these five residues to alanine produced
      either little or no negative effect on IRR pH-sensing activity. However, the
      triple mutation of M406, V407 and D408 (MVD) showed a strong negative effect,
      with a 4 fold decrease in IRR activity as estimated by in vitro
      autophosphorylation assay of solubilized receptors. The analysis of this mutant
      in intact cells revealed the absence of positive cooperativity. Unexpectedly, the
      double mutation of vicinal P436 and V437 (PV) exhibited a significant positive
      effect in the in vitro assay and partial positive cooperativity in the whole-cell
      assay. The role of FnIII domains was addressed by analyzing chimeras of IRR and
      IR. When the IRR FnIII domains were swapped with those of IR in different
      combinations, the activity was significantly reduced and positive cooperativity
      eliminated. However, two mutants with the targeted C-terminal part of IRR alpha
      subunit that lies within FnIII-2 domain and have been shown to be important for
      insulin binding by IR, appeared to be as active as wild-type IRR. On the basis of
      available data, we propose that IRR activation involves two separate centers of
      pH-dependent rearrangements that act synergistically to induce a major
      conformational change in the IRR molecule, resulting in internal kinase domains
      rapprochement and autophosphorylation.

PMID- 25597418
TI  - Cryptogenic stroke.
AB  - In about a quarter of ischaemic strokes the cause is undetermined, because the
      investigation is incomplete or delayed, because there are multiple causes or
      because the stroke is truly cryptogenic. Cryptogenic stroke can be further
      classified as non-embolic or embolic. Embolic stroke of undetermined source can
      be due to paroxysmal atrial fibrillation, minor emboligenic cardiac conditions,
      atheroembolism, cancer associated and paradoxical embolism through a patent
      foramen ovale (PFO) or less often a pulmonary fistula. Currently, risk factor
      control, statins and antiplatelets are the main therapeutic measures to prevent
      recurrent stroke. There is no evidence to implement routine closure of PFO in
      patients with cryptogenic stroke. Direct anticoagulants are being evaluated in
      randomized controlled trials including embolic stroke of undetermined source
      patients. Advances in high resolution ultrasound or magnetic resonance imaging of
      extracranial and intracranial vessels and of the heart and prolonged heart rhythm
      monitoring will be instrumental techniques to identify arterial and cardiac
      hidden causes of stroke. 

PMID- 25597419
TI  - Technological characterization of sheep production systems in Brazil.
AB  - Sheep production has expanded in Brazil focusing on lamb meat, mostly to meet
      demanding internal markets in the state of Sao Paulo. Such markets present a
      demand which internal production is insufficient to meet. However, sheep farmers
      face many technical difficulties to produce quality lambs at viable costs. This
      study aimed at investigating the main characteristics of sheep production systems
      of the state of Sao Paulo, Brazil, in order to provide resources for the
      development of technologies, policies and other initiatives focused on the
      activity. We designed in panel meetings the characteristics of representative
      sheep farms in five regions of the state, concerning: (i) property and manpower
      profile; (ii) flock; (iii) handling techniques; (iv) facilities and equipment;
      (v) food production; and (vi) technical indicators. Results demonstrate that the
      predominant sheep farming in the state employs low technology, presenting low
      productivity despite its evolution in recent years. We verified great technical
      deficiency regarding farmers, who are new in this business and usually do not
      have access to technologies. Producers' unawareness about basic handling
      procedures and techniques as well as their lack of flock records can contribute
      to the activity's unsustainability. There is need for improving rural extension
      and diffusion of technologies. 

PMID- 25597421
TI  - Sleeve endoscopic esophageal mucosotomy.

PMID- 25597420
TI  - ASGE Technology Committee systematic review and meta-analysis assessing the ASGE
      PIVI thresholds for adopting real-time endoscopic assessment of the histology of
      diminutive colorectal polyps.
AB  - In vivo real-time assessment of the histology of diminutive (<=5 mm) colorectal
      polyps detected at colonoscopy can be achieved by means of an "optical biopsy" by
      using currently available endoscopic technologies. This systematic review and
      meta-analysis was performed by the American Society for Gastrointestinal
      Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable
      performance thresholds outlined by an ASGE Preservation and Incorporation of
      Valuable endoscopic Innovations (PIVI) document for clinical adoption of these
      technologies have been met. We conducted direct meta-analyses calculating the
      pooled negative predictive value (NPV) for narrow-band imaging (NBI), i-SCAN, and
      Fujinon Intelligent Color Enhancement (FICE)-assisted optical biopsy for
      predicting adenomatous polyp histology of small/diminutive colorectal polyps. We
      also calculated the pooled percentage agreement with histopathology when
      assigning postpolypectomy surveillance intervals based on combining real-time
      optical biopsy of colorectal polyps 5 mm or smaller with histopathologic
      assessment of polyps larger than 5 mm. Random-effects meta-analysis models were
      used. Statistical heterogeneity was evaluated by means of I(2) statistics. Our
      meta-analyses indicate that optical biopsy with NBI, exceeds the NPV threshold
      for adenomatous polyp histology, supporting a "diagnose-and-leave" strategy for
      diminutive predicted nonneoplastic polyps in the rectosigmoid colon. The pooled
      NPV of NBI for adenomatous polyp histology by using the random-effects model was
      91% (95% confidence interval [CI], 88-94). This finding was associated with a
      high degree of heterogeneity (I(2) = 89%). Subgroup analysis indicated that the
      pooled NPV was greater than 90% for academic medical centers (91.8%; 95% CI, 89
      94), for experts (93%; 95% CI, 91-96), and when the optical biopsy assessment was
      made with high confidence (93%; 95% CI, 90-96). Our meta-analyses also indicate
      that the agreement in assignment of postpolypectomy surveillance intervals based
      on optical biopsy with NBI of diminutive colorectal polyps is 90% or greater in
      academic settings (91%; 95% CI, 86-95), with experienced endoscopists (92%; 95%
      CI, 88-96) and when optical biopsy assessments are made with high confidence
      (91%; 95% CI, 88-95). Our systematic review and meta-analysis confirms that the
      thresholds established by the ASGE PIVI for real-time endoscopic assessment of
      the histology of diminutive polyps have been met, at least with NBI optical
      biopsy, with endoscopists who are expert in using this advanced imaging
      technology and when assessments are made with high confidence. 

PMID- 25597422
TI  - The light at the end of the tunnel: a single-operator learning curve analysis for
      per oral endoscopic myotomy.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) represents a natural orifice
      transluminal endoscopic surgery approach to Heller myotomy. Our center was the
      first to offer POEM outside of Japan, allowing us to accumulate what is likely
      the highest single-operator POEM volume in the United States. OBJECTIVE: To
      define the POEM learning curve of a gastroenterologist by using a larger data set
      and more detailed statistical analysis than used in 2 other reports of POEM
      performed by surgeons. DESIGN: Prospective cohort study. SETTING: Tertiary-care
      academic medical center. PATIENTS: We analyzed the first 93 consecutive POEMs on
      patients with achalasia aged >18 years without contraindications to POEM
      performed by a single operator from October 2009 to November 2013. INTERVENTIONS:
      (1) Efficiency estimation via cumulative sum (CUSUM) analysis, (2) mastery
      estimation via penalized basis-spline regression and CUSUM analysis, (3)
      correlation of operator experience with clinical outcomes (Eckardt score
      improvement, lower esophageal sphincter pressure reduction) and technical errors
      (accidental mucosotomy rate), and (4) unadjusted and adjusted regression analysis
      to assess how patient characteristics affected procedure time by using a
      generalized linear model. MAIN OUTCOME MEASUREMENTS: Clinical outcomes, procedure
      time, technical errors. RESULTS: Efficiency was attained after 40 POEMs and
      mastery after 60 POEMs. When we used the adjusted regression analysis, only case
      number (operator experience) significantly affected procedure time (P < .0001).
      Improvements in clinical outcomes were excellent but not significantly affected
      by operator experience, as was the case with accidental mucosotomies. Procedure
      time was not significantly affected by age, sex, achalasia stage, baseline lower
      esophageal sphincter pressure, baseline Eckardt score, prior treatment of
      achalasia, prior botulinum toxin injection, incidence of accidental mucosotomies,
      length of myotomy, or type of knife used (all P > .05). LIMITATIONS: Our analysis
      may underestimate the number of POEMs required to achieve mastery for operators
      with limited or no endoscopic submucosal dissection experience. CONCLUSION: These
      results offer thresholds for efficiency and mastery of a single
      gastroenterologist operator that may guide the efforts of novice POEM operators.

PMID- 25597423
TI  - Peroral cholangioscopy-guided forceps biopsy to evaluate a cicatricial stricture
      of the biliary duct (with video).

PMID- 25597424
TI  - Identification of the geographical origins of pomelos using multielement
      fingerprinting.
AB  - Eighty pomelo samples and 80 soil samples were examined using a multielement
      component test to predict the geographical origins of pomelos produced in 4
      regions (Sichuan, Chongqing, Fujian, and Guangxi Provinces) of China. The
      concentrations of 8 elements were determined by atomic absorption spectrometry.
      Ca, K, and Na were the most abundant elements. Principal component analysis (PCA)
      and linear discriminant analysis (LDA) were applied to reduce the dimensionality
      of the multielement data from 8 to 2 while retaining the highest possible
      variance. Using PCA and LDA, 69.66% and 91.30%, respectively, of the pomelo
      origins were classified correctly using multielement variables, along with 67.06%
      and 83.40% for soil multielement analysis. Results indicated that the LDA method
      was more effective for geographical origin classification than PCA. The results
      of the multielement component test demonstrated its capability to screen pomelo
      origins rapidly. 

PMID- 25597425
TI  - Is hexagonal boron nitride always good as a substrate for carbon nanotube-based
      devices?
AB  - Hexagonal boron nitride sheets have been noted especially for their enhanced
      properties as substrates for sp(2) carbon-based nanodevices. To evaluate whether
      such enhanced properties would be retained under various realistic conditions, we
      investigate the structural and electronic properties of semiconducting carbon
      nanotubes on perfect and defective hexagonal boron nitride sheets under an
      external electric field as well as with a metal impurity, using density
      functional theory. We verify that the use of a perfect hexagonal boron nitride
      sheet as a substrate indeed improves the device performances of carbon nanotubes,
      compared with the use of conventional substrates such as SiO2. We further show
      that even the hexagonal boron nitride with some defects can show better
      performance as a substrate. Our calculations, on the other hand, also suggest
      that some defective boron nitride layers with a monovacancy and a nickel impurity
      could bring about poor device behavior since the imperfections impair electrical
      conductivity due to residual scattering under an applied electric field. 

PMID- 25597426
TI  - Epithelial polarity--generating and integrating signals from the ECM with
      integrins.
AB  - Epithelial cells are important building blocks of most tissues and the corner
      stone of tissue architectures that allow directional transport of nutrients, ions
      and waste products in and out of the body. In tissues composed of millions of
      cells every individual cell needs to make right decisions when to differentiate,
      migrate, divide or die. Tight control of such fundamental cell-level processes
      ensures proper tissue morphogenesis, homeostasis and function. Cellular decisions
      are guided by biochemical and mechanical cues from their immediate
      microenvironment that consists of the extracellular matrix (ECM), neighboring
      cells and soluble factors. Generation of two distinct surfaces one facing the
      outside world (the apical domain) and the other contacting the neighboring cells
      and basal ECM (basolateral domain) is the most fundamental property of epithelial
      cells. The cues from the ECM are of particular importance in this process and
      communication between the cells and the ECM is largely mediated by transmembrane
      ECM receptors. Integrins constitute the largest family of such receptors binding
      to the ECM. Integrins have been shown to be essential for the establishment of
      initial polarity cues that define the position of the basal domain and thereby
      govern the orientation of the forming apico-basal axis. In this review I will
      discuss the multifaceted roles of integrins in epithelial cells with a particular
      focus on recent developments unveiling the specific functions of the different
      integrin heterodimers in regulating epithelial cell polarization and
      morphogenesis. 

PMID- 25597427
TI  - Effect of differentiation on endocytic profiles of endothelial and epithelial
      cell culture models.
AB  - Understanding mechanisms of endocytosis and trafficking of nanoparticles through
      endothelial and epithelial barriers leads potentially to improved efficacy of
      nanoparticulate drug delivery systems. Detailed characterizations of cell models
      with respect to endocytic pathway expression and activity (endocytic profiling)
      should facilitate data interpretation. We performed endocytic profiling of CaCo-2
      and hCMEC/D3 cell lines, widely used as human intestinal and blood-brain barrier
      permeability models, respectively, during cell differentiation. Furthermore, we
      compared endocytic profiles of cell lines with those of primary cells. Expression
      of genes involved in specific endocytic pathways was analyzed at mRNA levels by
      quantitative real time PCR. Where possible, the respective protein levels were
      analyzed by Western blotting, and endocytic activities of cells were analyzed by
      flow cytometry. We showed that differentiated CaCo-2 cells formed tight, well
      polarized monolayers with reduced endocytic activity accompanied by reduced mRNA
      expression of most of the endocytosis-related genes. In contrast, hCMEC/D3 cells
      formed a leaky, less polarized barrier, and in vitro differentiation had little
      effect on either the expression of endocytosis-related genes or endocytic
      activity of these cells. Endocytic profiling of in vitro models and comparison
      with primary cells is an important measure to avoid misleading conclusions in
      nanoparticle permeation studies. 

PMID- 25597428
TI  - Purification and characterization of a novel exopolysaccharides produced by
      Lactobacillus sp. Ca6.
AB  - This study was undertaken to investigate the ability of ten lactic acid bacterial
      strains to produce exopolysaccharides (EPS) on MRS broth containing 4% sucrose. A
      maximum EPS production yield of 2.4 g/l was obtained by strain Lactobacillus sp.
      Ca6. The results from thin layer chromatography (TLC) and high performance
      chromatography (HPLC) analyses showed that the EPS produced was a polymer of
      glucose. Further FTIR spectroscopic analysis revealed the presence of carboxyl,
      hydroxyl and amide groups corresponding to a typical EPS. In addition to EPS
      production, Lactobacillus sp. Ca6 displayed good probiotic properties
      (antimicrobial activities and sensitivity to several antibiotics) and resistance
      to acidic condition (pH 2) and 5% bile bovine. Overall, the findings indicate
      that this strain has a number of promising properties that make it a potential
      promising candidate for future application as a food additive.

PMID- 25597430
TI  - Description of a new surface morphology for chitin extracted from wings of
      cockroach (Periplaneta americana).
AB  - In this study a new morphology of chitin, which could find wide applications in
      the fields of medicine, pharmacy, agriculture, food and textiles, has been
      described. The chitin was isolated from the wings of Periplaneta americana
      employing a conventional method. Considering chitin isolation studies conducted
      previously, chitin has three surface morphologies, which are (1) hard and rough
      surface without pores or nanofibers, (2) surface solely composed of nanofibers
      and (3) surfaces with both pores and nanofibers. In this study, the surface of
      the chitin, examined with environmental scanning electron microscopy (ESEM), only
      has oval nanopores (230-510 nm) without nanofibers, and this is different from
      the above mentioned surface morphologies. The nanopores are not distributed on
      the chitin surface randomly. Typically, there is a pore in the center that is
      surrounded by six or seven other pores in an ordered manner. Structures similar
      to cell walls exist between the pores. Chitin with the new surface morphology was
      characterized using Fourier transform infrared spectroscopy (FTIR),
      thermogravimetric analysis (TG), X-ray diffraction (XRD) and elemental analysis.

PMID- 25597429
TI  - A Huaier polysaccharide restrains hepatocellular carcinoma growth and metastasis
      by suppression angiogenesis.
AB  - Hepatocellular carcinoma (HCC) is a highly metastatic cancer. Huaier
      polysaccharide (TP-1) is a naturally occurring bioactive macromolecule, found in
      Huaier fungus and has been shown to exert in vitro antitumor and antimetastasis
      for HCC, but no study has addressed in vivo efficacy and mechanisms of action.
      Presently, we found that TP-1 at doses of 0.5, 1 and 2mg/kg significantly
      inhibited tumor growth and metastasis to the lung in mice bearing HCC SMMC-7721
      tumors without toxicity. The analysis of tumors by immunohistochemistry
      demonstrated that TP-1 inhibited PCNA expression, increased the number of TUNEL
      positive cells and reduced microvessel density (MVD) to achieve this effect.
      Furthermore, TP-1 administration reduced the protein expression of hypoxia
      inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), AUF-1
      and AEG-1, in tumor tissues. Taken together, our data suggested that the
      antitumor and anti-metastatic activities of TP-1 might be at least partially
      through down-regulation of HIF-1alpha/VEGF and AUF-1/AEG-1 signaling pathways. 

PMID- 25597431
TI  - The novel synthesis of magnetically chitosan/carbon nanotube composites and their
      catalytic applications.
AB  - Chitosan-modified magnetic carbon nanotubes (CS-MCNTs) were synthesized and were
      investigated by FT-IR, EDX, FE-SEM, elemental analysis, XRD, VSM and TGA. In
      order to synthesize the CS-MCNTs composites, Fe3O4 decorated carbon nanotubes
      (CNTs-Fe3O4) were modified with a silica layer by the ammonia-catalysed
      hydrolysis of tetraethyl orthosilicate (CNTs-Fe3O4@SiO2). Then, CS-MCNTs were
      successfully grafted on the surface of CNTs-Fe3O4@SiO2via a suspension cross
      linking method. The CS-MCNT was found to be an excellent heterogeneous catalyst
      for the synthesis of 1,4-dihydropyridines (DHPs). The attractive advantages of
      the present process include short reaction times, milder and cleaner conditions,
      higher purity and yields, easy isolation of products, easier work-up procedure
      and lower generation of waste or pollutions. This catalyst was easily separated
      by an external magnet and the recovered catalyst was reused several times without
      any significant loss of activity. A combination of the advantages of CNTs,
      chitosan and magnetic nanoparticles provides an important methodology for
      carrying out catalytic transformations. Therefore, this method provides a green
      and much improved protocol over the existing methods. 

PMID- 25597432
TI  - Prevalence of alcohol-interactive prescription medication use among current
      drinkers: United States, 1999 to 2010.
AB  - BACKGROUND: The majority of Americans consume alcoholic beverages. Alcohol
      interacts negatively with numerous commonly prescribed medications. Yet, on a
      population level, little is known about use of alcohol-interactive (AI)
      prescription medications among drinkers. The purpose of our study was to
      determine the prevalence of AI prescription medication use among current drinkers
      in the U.S. population. METHODS: Data were from the National Health and Nutrition
      Examination Survey (NHANES 1999 to 2010); 26,657 adults aged >=20 years had data
      on past year alcohol consumption and past month prescription medication use.
      Analyses were adjusted for covariates: age, race/ethnicity, education, marital
      status, and smoking. Statistical procedures accounted for survey stratification,
      clustering, and nonresponse. Analyses were weighted to be nationally
      representative. RESULTS: The unadjusted total prevalence of AI medication use was
      42.8% (95% confidence interval [CI] 41.5 to 44.0). Among current drinkers,
      adjusted prevalence was 41.5% (CI 40.3 to 42.7). Among participants aged >=65
      total prevalence of AI medication use was 78.6% (CI 77.3 to 79.9) and adjusted
      prevalence among current drinkers was 77.8% (CI 75.7 to 79.7). The AI medications
      most commonly used by current drinkers were cardiovascular agents, central
      nervous system agents, and metabolic agents. CONCLUSIONS: Our results suggest
      that there could be substantial simultaneous exposure to alcohol and AI
      prescription medications in the U.S. population. Given the adverse health risks
      of combining alcohol with AI prescription medications, future efforts are needed
      to collect data to determine actual simultaneous prevalence.

PMID- 25597434
TI  - Simple self-report FRAIL scale might be more closely associated with dialysis
      complications than other frailty screening instruments in rural chronic dialysis
      patients.
AB  - AIM: Despite the perceived importance of frailty, few studies focus on its impact
      on rural patients undergoing chronic dialysis. Comparison of different self
      report questionnaires in assessing frailty among these patients has not been
      attempted before. METHODS: A prospectively enrolled chronic dialysis cohort from
      a rural centre was recruited for analysis. Six types of self-report
      questionnaires were administered to these patients. Clinical and dialysis-related
      laboratory parameters were collected. Correlation analyses between questionnaire
      results and dialysis complications were performed, and variables demonstrating
      significant correlations were entered into multivariate regression models to
      determine their independent associations. RESULTS: Six types of questionnaire
      (Strawbridge questionnaire, Edmonton Frail Scale, simple FRAIL scale, Groningen
      Frail Indicator, G8 questionnaire, and Tilburg Frail Indicator) were provided to
      rural patients undergoing chronic dialysis. Scores from each questionnaire showed
      significant association with each other, except the G8 questionnaire. Scores from
      the simple FRAIL scale correlated significantly with age (P = 0.02), female
      gender (P = 0.03), higher Liu's comorbidity index (P = 0.02), lower serum albumin
      (P = 0.03) and creatinine levels (P < 0.01), and higher ferritin levels (P =
      0.02). The other five questionnaires did not show consistently significant
      relationships with important dialysis-related complications. Multivariate linear
      regression analysis identified an independently negative association between
      serum albumin and the simple FRAIL scale results (P = 0.01). CONCLUSION: This is
      the first study establishing the utility of different self-report questionnaires
      for assessing frailty in chronic dialysis patients. The simple FRAIL scale scores
      might demonstrate a closer relationship with dialysis-related complications.

PMID- 25597435
TI  - Reader responses to the ethics forum: room for multiple perspectives.

PMID- 25597433
TI  - The mitochondrial aspartate/glutamate carrier isoform 1 gene expression is
      regulated by CREB in neuronal cells.
AB  - The aspartate/glutamate carrier isoform 1 is an essential mitochondrial
      transporter that exchanges intramitochondrial aspartate and cytosolic glutamate
      across the inner mitochondrial membrane. It is expressed in brain, heart and
      muscle and is involved in important biological processes, including myelination.
      However, the signals that regulate the expression of this transporter are still
      largely unknown. In this study we first identify a CREB binding site within the
      aspartate/glutamate carrier gene promoter that acts as a strong enhancer element
      in neuronal SH-SY5Y cells. This element is regulated by active, phosphorylated
      CREB protein and by signal pathways that modify the activity of CREB itself and,
      most noticeably, by intracellular Ca(2+) levels. Specifically,
      aspartate/glutamate carrier gene expression is induced via CREB by forskolin
      while it is inhibited by the PKA inhibitor, H89. Furthermore, the CREB-induced
      activation of gene expression is increased by thapsigargin, which enhances
      cytosolic Ca(2+), while it is inhibited by BAPTA-AM that reduces cytosolic Ca(2+)
      or by STO-609, which inhibits CaMK-IV phosphorylation. We further show that CREB
      dependent regulation of aspartate/glutamate carrier gene expression occurs in
      neuronal cells in response to pathological (inflammation) and physiological
      (differentiation) conditions. Since this carrier is necessary for neuronal
      functions and is involved in myelinogenesis, our results highlight that targeting
      of CREB activity and Ca(2+) might be therapeutically exploited to increase
      aspartate/glutamate carrier gene expression in neurodegenerative diseases. 

PMID- 25597436
TI  - Response to ethics forum: Low dose targeted drug approaches need highlighting and
      consideration.

PMID- 25597437
TI  - Intrathecal therapy: broadening the perspective.

PMID- 25597438
TI  - Pregabalin in the treatment of herpetic neuralgia: results of a multicenter
      Chinese study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy, impact on quality
      of life, and safety of pregabalin for the treatment of acute herpetic neuralgia
      (AHN) and subacute herpetic neuralgia (SHN). DESIGN: Multicenter, parallel-group,
      single-blind, 4-week, randomized clinical trial. SETTING: Conducted in the
      department of pain clinic of participating hospitals. SUBJECTS: Three hundred
      patients with AHN or SHN (of which 239 completed the study). METHODS: Patients
      were treated with oxycodone (A group) or combination of oxycodone and pregabalin
      (B group). Patients with AHN belonged to A1 group and B1 group. Patients with SHN
      belonged to A2 group and B2 group. Pain intensity was rated on an 11-point
      numerical rating scale (NRS). Other outcomes included mean daily oxycodone doses,
      quality of life, and adverse effects. RESULTS: Pregabalin-treated patients had
      greater NRS decrement: 74% in B1 (vs 58% in A1; P < 0.05); 69% in B2 (vs 53% in
      A2; P < 0.05). Significant improvement in quality of life was observed in all
      groups, and pregabalin-treated patients improved more, with 72.7% in B1 (vs 63.7%
      in A1; P < 0.05) and 74.5% in B2 (vs 59.6% in A2; P < 0.05). The maximum
      tolerated dose of oxycodone for pregabalin-treated patients was lower. Pregabalin
      had acceptable tolerability. CONCLUSIONS: Both combination therapy with oxycodone
      plus pregabalin and oxycodone monotherapy were effective and safe for herpetic
      neuralgia. In addition, subjects on combination therapy showed shortened time to
      pain relief, reduced pain intensity, and greater improvement than oxycodone
      alone.

PMID- 25597441
TI  - Bovine Arboviruses in Culicoides Biting Midges and Sentinel Cattle in Southern
      Japan from 2003 to 2013.
AB  - Epizootic congenital abnormalities, encephalomyelitis and febrile illnesses in
      cattle caused by arthropod-borne viruses (arboviruses) are prevalent in Japan.
      Causative viruses including orthobunyaviruses, orbiviruses and rhabdovirus are
      thought to be transmitted by Culicoides biting midges. Recently, the incursions
      of several arboviruses, potentially Culicoides-borne, were newly confirmed in
      Japan. However, their spread pattern and exact vector species are currently
      uncertain. Attempts to isolate arboviruses from Culicoides biting midges and
      sentinel cattle were conducted in Kagoshima, located at the southernmost end of
      the main islands of Japan, a potentially high-risk area for incursion of
      arboviral diseases and outbreak of endemic ones. Seventy-eight isolates
      comprising Akabane, Peaton and Sathuperi viruses of the genus Orthobunyavirus of
      the family Bunyaviridae, bluetongue virus serotype 16, D'Aguilar virus, Bunyip
      Creek virus and epizootic haemorrhagic disease virus serotype 1 of the genus
      Orbivirus of the family Reoviridae, a potentially novel rhabdovirus of the genus
      Ephemerovirus and unidentified orbivirus-like viruses were obtained from
      Culicoides biting midges and sentinel cattle between 2003 and 2013. Akabane,
      Sathuperi, D'Aguilar and Bunyip Creek viruses were selectively isolated from
      Culicoides oxystoma, suggesting this vector's responsibility for these arbovirus
      outbreaks. The results of virus isolation also implied that C. tainanus, C.
      jacobsoni and C. punctatus are competent for the transmission of bluetongue virus
      serotype 16, Peaton virus and epizootic haemorrhagic disease virus serotype 1,
      respectively. Our monitoring in Culicoides biting midges and sentinel cattle
      detected the circulation of Akabane virus just prior to the accumulations of
      bovine congenital abnormalities and encephalomyelitis by it around study sites in
      2003, 2006, 2008 and 2013. Silent circulations of the other arboviruses,
      including potentially new viruses, were also detected during the study period.

PMID- 25597442
TI  - Suppression of antigen presentation by IL-10.
AB  - Regulated antigen presentation to immune cells determines the effectiveness of an
      immune response. IL-10 is an immunosuppressive cytokine that regulates immune
      responses by inhibiting the ability of APCs to present antigens to T cells in a
      variety of ways. The mechanisms of IL-10-mediated immunosuppression include
      interference in TLR-mediated or IFNgamma-mediated dendritic cell (DC) and
      macrophage activation as well as direct induction of genes that suppress APC
      function. In this review we will discuss current studies exploring the molecular
      mechanisms by which IL-10 suppresses APC function. 

PMID- 25597444
TI  - Post-translational modifications as key regulators of bacterial metabolic fluxes.
AB  - In order to survive and compete in natural settings, bacteria must excel at
      quickly adapting their metabolism to fluctuations in nutrient availability and
      other environmental variables. This necessitates fast-acting post-translational
      regulatory mechanisms, that is, allostery or covalent modification, to control
      metabolic flux. While allosteric regulation has long been a well-established
      strategy for regulating metabolic enzyme activity in bacteria, covalent post
      translational modes of regulation, such as phosphorylation or acetylation, have
      previously been regarded as regulatory mechanisms employed primarily by
      eukaryotic organisms. Recent findings, however, have shifted this perception and
      point to a widespread role for covalent posttranslational modification in the
      regulation of metabolic enzymes and fluxes in bacteria. This review provides an
      outline of the exciting recent advances in this area. 

PMID- 25597443
TI  - On the evolution of bacterial multicellularity.
AB  - Multicellularity is one of the most prevalent evolutionary innovations and
      nowhere is this more apparent than in the bacterial world, which contains many
      examples of multicellular organisms in a surprising array of forms. Due to their
      experimental accessibility and the large and diverse genomic data available,
      bacteria enable us to probe fundamental aspects of the origins of
      multicellularity. Here we discuss examples of multicellular behaviors in
      bacteria, the selective pressures that may have led to their evolution, possible
      origins and intermediate stages, and whether the ubiquity of apparently
      convergent multicellular forms argues for its inevitability. 

PMID- 25597445
TI  - Incorporating relaxivities to more accurately reconstruct MR images.
AB  - PURPOSE: To develop a mathematical model that incorporates the magnetic resonance
      relaxivities into the image reconstruction process in a single step. MATERIALS
      AND METHODS: In magnetic resonance imaging, the complex-valued measurements of
      the acquired signal at each point in frequency space are expressed as a Fourier
      transformation of the proton spin density weighted by Fourier encoding anomalies:
      T2(*), T1, and a phase determined by magnetic field inhomogeneity (?B) according
      to the MR signal equation. Such anomalies alter the expected symmetry and the
      signal strength of the k-space observations, resulting in images distorted by
      image warping, blurring, and loss in image intensity. Although T1 on tissue
      relaxation time provides valuable quantitative information on tissue
      characteristics, the T1 recovery term is typically neglected by assuming a long
      repetition time. In this study, the linear framework presented in the work of
      Rowe et al., 2007, and of Nencka et al., 2009 is extended to develop a Fourier
      reconstruction operation in terms of a real-valued isomorphism that incorporates
      the effects of T2(*), ?B, and T1. This framework provides a way to precisely
      quantify the statistical properties of the corrected image-space data by offering
      a linear relationship between the observed frequency space measurements and
      reconstructed corrected image-space measurements. The model is illustrated both
      on theoretical data generated by considering T2(*), T1, and/or ?B effects, and on
      experimentally acquired fMRI data by focusing on the incorporation of T1. A
      comparison is also made between the activation statistics computed from the
      reconstructed data with and without the incorporation of T1 effects. RESULT:
      Accounting for T1 effects in image reconstruction is shown to recover image
      contrast that exists prior to T1 equilibrium. The incorporation of T1 is also
      shown to induce negligible correlation in reconstructed images and preserve
      functional activations. CONCLUSION: With the use of the proposed method, the
      effects of T2(*) and ?B can be corrected, and T1 can be incorporated into the
      time series image-space data during image reconstruction in a single step.
      Incorporation of T1 provides improved tissue segmentation over the course of time
      series and therefore can improve the precision of motion correction and image
      registration.

PMID- 25597446
TI  - Evaluating endogenous repair of focal cartilage defects in C57BL/6 and MRL/MpJ
      mice using 9.4T magnetic resonance imaging: A pilot study.
AB  - The use of magnetic resonance imaging (MRI) for evaluating joint injuries is
      often considered superior to radiography due to the capacity of MRI for
      visualizing both soft and hard tissues. While longitudinal studies regarding
      cartilage repair have been undertaken on patients and in larger animal models, a
      method has yet to be developed for mouse cartilage to be repeatedly and non
      invasively evaluated over time. The aim of this pilot study was to investigate if
      morphological changes following a focal cartilage injury in mice could be
      measured by 9.4T magnetic resonance imaging. Focal cartilage defects were induced
      in the left knee of 4-6weeks old C57BL/6 and MRL/MpJ mice. At endpoints 0, 2, and
      4weeks post-injury, legs were dissected out and imaged ex vivo. The defect could
      be detected by MRI immediately after injury, appearing as a hyperintense focal
      point and with size similar to that of the surgical tool used. Defects were
      visible in both strains up to 4weeks post-injury, although signal intensity
      decreased over time. One C57BL/6 in particular, displayed extensive fibrosis in
      the patellar tendon at 4weeks as assessed by histology, while the MR images of
      the same animal displayed a clear, structural distinction between the patella and
      the new tissue growth. Overall, our results suggest that MRI could be used for
      longitudinal studies in murine cartilage injury models to evaluate certain
      characteristics of repair not detectable through histology. 

PMID- 25597448
TI  - [Hypertension: the real challenge is to better care].

PMID- 25597449
TI  - Anisotropic growth of buckling-driven wrinkles in graphene monolayer.
AB  - We theoretically and numerically investigate the growth of buckling-driven
      wrinkles in graphene monolayers. It is found that the growth of buckling-driven
      wrinkles in a graphene monolayer is remarkably chirality- and size-dependent. In
      small sizes, the flexural response of a graphene sheet cannot be accurately
      described by the classical Euler regime, and the non-continuum effect leads to
      zigzag-along-preferred buckling. With the increase of size, the width/length
      ratio alpha of the compressed region plays an important role in the growth of
      buckling-driven wrinkles. When alpha < 0.5, the oblique buckling happens in
      armchair-along compression; when 0.5 < alpha < 1.0, the effect of edge warp leads
      to zigzag-along-preferred buckling. When 1.0 < alpha < 3.0, the potential energy
      density difference due to chiral bending stiffness leads to armchair-along
      preferred buckling. When alpha > 3.0, the non-continuum effect and chiral bending
      stiffness can both be neglected, and the buckling in a graphene monolayer is
      isotropic. The chirality-along-preferred transition of compressed buckling in a
      graphene monolayer leads to an improved fundamental understanding of the dynamics
      mechanism of graphene-based nanodevices, especially for the nanodevices with high
      frequency response.

PMID- 25597447
TI  - Manganese binding properties of human calprotectin under conditions of high and
      low calcium: X-ray crystallographic and advanced electron paramagnetic resonance
      spectroscopic analysis.
AB  - The antimicrobial protein calprotectin (CP), a hetero-oligomer of the S100 family
      members S100A8 and S100A9, is the only identified mammalian Mn(II)-sequestering
      protein. Human CP uses Ca(II) ions to tune its Mn(II) affinity at a biologically
      unprecedented hexahistidine site that forms at the S100A8/S100A9 interface, and
      the molecular basis for this phenomenon requires elucidation. Herein, we
      investigate the remarkable Mn(II) coordination chemistry of human CP using X-ray
      crystallography as well as continuous-wave (CW) and pulse electron paramagnetic
      resonance (EPR) spectroscopies. An X-ray crystallographic structure of Mn(II)-CP
      containing one Mn(II), two Ca(II), and two Na(I) ions per CP heterodimer is
      reported. The CW EPR spectrum of Ca(II)- and Mn(II)-bound CP prepared with a
      10:0.9:1 Ca(II):Mn(II):CP ratio is characterized by an unusually low zero-field
      splitting of 485 MHz (E/D = 0.30) for the S = 5/2 Mn(II) ion, consistent with the
      high symmetry of the His6 binding site observed crystallographically. Results
      from electron spin-echo envelope modulation and electron-nuclear double resonance
      experiments reveal that the six Mn(II)-coordinating histidine residues of Ca(II)-
      and Mn(II)-bound CP are spectroscopically equivalent. The observed (15)N (I =
      1/2) hyperfine couplings (A) arise from two distinct classes of nitrogen atoms:
      the coordinating epsilon-nitrogen of the imidazole ring of each histidine ligand
      (A = [3.45, 3.71, 5.91] MHz) and the distal delta-nitrogen (A = [0.11, 0.18,
      0.42] MHz). In the absence of Ca(II), the binding affinity of CP for Mn(II) drops
      by two to three orders of magnitude and coincides with Mn(II) binding at the His6
      site as well as other sites. This study demonstrates the role of Ca(II) in
      enabling high-affinity and specific binding of Mn(II) to the His6 site of human
      calprotectin. 

PMID- 25597450
TI  - Biodegradation of carbon nanohorns in macrophage cells.
AB  - With the rapid developments in the medical applications of carbon nanomaterials
      such as carbon nanohorns (CNHs), carbon nanotubes, and graphene based
      nanomaterials, understanding the long-term fate, health impact, excretion, and
      degradation of these materials has become crucial. Herein, the in vitro
      biodegradation of CNHs was determined using a non-cellular enzymatic oxidation
      method and two types of macrophage cell lines. Approximately 60% of the CNHs was
      degraded within 24 h in a phosphate buffer solution containing myeloperoxidase.
      Furthermore, approximately 30% of the CNHs was degraded by both RAW 264.7 and THP
      1 macrophage cells within 9 days. Inflammation markers such as pro-inflammatory
      cytokines interleukin 6 and tumor necrosis factor alpha were not induced by
      exposure to CNHs. However, reactive oxygen species were generated by the
      macrophage cells after uptake of CNHs, suggesting that these species were
      actively involved in the degradation of the nanomaterials rather than in an
      inflammatory pathway induction. 

PMID- 25597451
TI  - Characterization of magnesia-doped yttria-stabilized zirconia powders for dental
      technology applications.
AB  - PURPOSE: This paper is focused on the works concerning preparation of zirconium
      oxide ceramic blocks recommended for CAD/CAM systems used in prosthetic dentistry
      for manufacturing fixed prosthetic restorations. METHODS: Zirconium-yttrium
      magnesium mixed ceramic oxides were prepared by sol-gel method via hydrolysis and
      condensation of zirconium alkoxide precursor (zirconium (IV) propoxide) with
      yttrium and magnesium nitrates diluted in 2-propanol. The aim of this work was to
      obtain 2% mol yttria-stabilized zirconia ceramic powders with magnesium as an
      additional tetragonal ZrO2 phase stabilizer in amount between 2/6% mol (with 2%
      variable). Prepared gels were dried (24 h at 65  degrees C). Obtained powders
      were mixed with binder (carboxymethyl cellulose) and uniaxial pressed into
      specimens with a dimensions 38 * 22 * 6 mm. Afterwards green bodies were sintered
      in range of temperature between 1350-1550  degrees C. Powders and blocks were
      characterized by Scanning Electron Microscopy, Fourier Transform Infrared
      Spectroscopy, Specific Area Measurement. RESULTS: Highly homogeneous powders with
      a low open porosity were obtained. Prepared blocks after sintering showed
      numerous cracks. Nevertheless blocks were fine grained and showed quite
      reproducible chemical composition. CONCLUSION: A sol gel wet chemical route of
      powder synthesis allow us to obtain high homogenous ceramic materials with
      inconsiderable amount of pores with low variation in dimensions. In spite of a
      reproducible synthesis methods of a ceramic powders, applied to prepare green
      bodies procedure and sintering manner do not allowed to obtain zirconia cermic
      blocks free from cracks.

PMID- 25597453
TI  - Effects of the electronic structure of five-membered N-heterocyclic carbenes on
      insertion of silanes and boranes into the NHC C-N bond.
AB  - The effect of varying the N-heterocyclic carbene (NHC) ligand on ring expansion
      and endocyclic C-N activation of NHCs by silanes and boranes has been
      investigated with theoretical methods. Five common NHCs were considered,
      including unsaturated, saturated, 3,4-methyl, 3,4-chloro substituted five
      membered NHCs and a fused benzimidazole NHC. The substrates considered were
      Ph2SiH2 (with two hydrides migrating to the carbene carbon), H2BMe (two hydrides
      migrating), HBMe2 (hydride migration, followed by methyl migration) and BMe3 (two
      methyls migrating). Consistent with experimental observations, it was found that
      the kinetic barrier is lowest for the saturated NHC. The barrier is also quite
      low for the benzimidazole NHC. It was determined that the partial positive charge
      on the central carbene carbon in the initial adduct is inversely proportional to
      the magnitude of the activation barrier. 

PMID- 25597452
TI  - Online multi-channel microfluidic chip-mass spectrometry and its application for
      quantifying noncovalent protein-protein interactions.
AB  - To establish an automatic and online microfluidic chip-mass spectrometry (chip
      MS) system, a device was designed and fabricated for microsampling by a hybrid
      capillary. The movement of the capillary was programmed by a computer to aspirate
      samples from different microfluidic channels in the form of microdroplets
      (typically tens of nanoliters in volume), which were separated by air plugs. The
      droplets were then directly analyzed by MS via paper spray ionization without any
      pretreatment. The feasibility and performance were demonstrated by a
      concentration gradient experiment. Furthermore, after eliminating the effect of
      nonuniform response factors by an internal standard method, determination of the
      association constant within a noncovalent protein-protein complex was
      successfully accomplished with the MS-based titration indicating the versatility
      and the potential of this novel platform for widespread applications. 

PMID- 25597454
TI  - Highly selective visible light-induced Ti-O bond splitting in an ansa-titanocene
      dihydroxido complex.
AB  - Irradiation of a substituted ansa-titanocene(IV) dihydroxido complex with visible
      light induces Ti-O bond dissociation. In contrast to previous studies on
      structurally similar unbridged complexes, no side reactions are observed and
      formation of the Ti(III) species is highly selective. The formation of OH
      radicals was proved using a biradicaloid species.

PMID- 25597455
TI  - Vestibular assessment: it's complicated.

PMID- 25597456
TI  - Factors affecting reliability and validity of self-directed automatic in situ
      audiometry: implications for self-fitting hearing AIDS.
AB  - BACKGROUND: A reliable and valid method for the automatic in situ measurement of
      hearing thresholds is a prerequisite for the feasibility of a self-fitting
      hearing aid, whether such a device becomes an automated component of an
      audiological management program or is fitted by the user independently of a
      clinician. Issues that must be addressed before implementation of the procedure
      into a self-fitting hearing aid include the role of real-ear-to-dial difference
      correction factors in ensuring accurate results and the ability of potential
      users to successfully self-direct the procedure. PURPOSE: The purpose of this
      study was to evaluate the reliability and validity of an automatic audiometry
      algorithm that is fully implemented in a wearable hearing aid, to determine to
      what extent reliability and validity are affected when the procedure is self
      directed by the user, and to investigate contributors to a successful outcome.
      RESEARCH DESIGN: Design was a two-phase correlational study. STUDY SAMPLE: A
      total of 60 adults with mild to moderately severe hearing loss participated in
      both studies: 20 in Study 1 and 40 in Study 2. Twenty-seven participants in Study
      2 attended with a partner. Participants in both phases were selected for
      inclusion if their thresholds were within the output limitations of the test
      device. DATA COLLECTION AND ANALYSIS: In both phases, participants performed
      automatic audiometry through a receiver-in-canal, behind-the-ear hearing aid
      coupled to an open dome. In Study 1, the experimenter directed the task. In Study
      2, participants followed a set of written, illustrated instructions to perform
      automatic audiometry independently of the experimenter, with optional assistance
      from a lay partner. Standardized measures of hearing aid self-efficacy, locus of
      control, cognitive function, health literacy, and manual dexterity were
      administered. Statistical analysis examined the repeatability of automatic
      audiometry; the match between automatically and manually measured thresholds; and
      contributors to successful, independent completion of the automatic audiometry
      procedure. RESULTS: When the procedure was directed by an audiologist, automatic
      audiometry yielded reliable and valid thresholds. Reliability and validity were
      negatively affected when the procedure was self-directed by the user, but the
      results were still clinically acceptable: test-retest correspondence was 10 dB or
      lower in 97% of cases, and 91% of automatic thresholds were within 10 dB of their
      manual counterparts. However, only 58% of participants were able to achieve a
      complete audiogram in both ears. Cognitive function significantly influenced
      accurate and independent performance of the automatic audiometry procedure;
      accuracy was further affected by locus of control and level of education. Several
      characteristics of the automatic audiometry algorithm played an additional role
      in the outcome. CONCLUSIONS: Average transducer- and coupling-specific correction
      factors are sufficient for a self-directed in situ audiometry procedure to yield
      clinically reliable and valid hearing thresholds. Before implementation in a self
      fitting hearing aid, however, the algorithm and test instructions should be
      refined in an effort to increase the proportion of users who are able to achieve
      complete audiometric results. Further evaluation of the procedure, particularly
      among populations likely to form the primary audience of a self-fitting hearing
      aid, should be undertaken.

PMID- 25597457
TI  - Generalization of sensory auditory learning to top-down skills in a randomized
      controlled trial.
AB  - BACKGROUND: Research has shown that auditory training improves auditory sensory
      skills; however, it is unclear whether this improvement is transferred to top
      down skills, such as memory, attention, and language, and whether it depends on
      group characteristics in regard to memory and attention skills. PURPOSE: The
      primary goal of this research was to investigate the generalization of learning
      from auditory sensory skills to top-down skills such as memory, attention, and
      language. We also aimed to compare whether this generalization process occurs in
      the same way among typically developing children and children with speech sound
      disorder. RESEARCH DESIGN: This study was a randomized controlled trial. STUDY
      SAMPLE: Typically developing 7- to 12-yr-old children and children with speech
      sound disorder were separated into four groups: a trained control group (TDT; n =
      10, age 9.6 +/- 2.0 yr), a nontrained control group (TDNT; n = 11, age 8.2 +/-
      1.6 yr), a trained study group (SSDT; n = 10, age 7.7 +/- 1.2 yr), and a
      nontrained study group (SSDNT; n = 8, age 8.6 +/- 1.2 yr). INTERVENTION: Both
      trained groups underwent a computerized, nonverbal auditory training that focused
      on frequency discrimination, ordering, and backward-masking tasks. The training
      consisted of twelve 45 min sessions, once a week, for a total of 9 hr of
      training, approximately. DATA COLLECTION AND ANALYSIS: Near-transfer (Gap-In
      Noise [GIN] and Frequency Pattern Test) and far-transfer measures (auditory and
      visual sustained attention tests, phonological working memory and language tests)
      were applied before and after training. The results were analyzed using a 2 * 2 *
      2 mixed-model analysis of variance with the group and training as the between
      group variables and the period as the within-group variable. The significance
      threshold was p <= 0.05. RESULTS: There was a group * period * training
      interaction for GIN [F(1.35) = 7.18, p = 0.011], indicating a significant
      threshold reduction only for the TDT group (Tukey multiple comparisons). There
      was a significant group * period interaction [F(1.35) = 5.52, p = 0.025] and a
      training * period interaction for visual reaction time [F(1.35) = 4.20, p =
      0.048], indicating improvement in the SSDT group and worsening in both nontrained
      groups. There was also a significant group * training * period interaction
      [F(1.35) = 4.27, p = 0.046] for the auditory false alarms, with a significant
      improvement after training only for the SSDT group. Analysis of variance also
      revealed that all groups exhibited approximately the same level of gains for all
      measures, except for GIN [F(3,38) = 4.261, p = 0.011] and visual response time
      [F(3.38) = 4.069, p = 0.014]. CONCLUSIONS: After training, the TDT group
      demonstrated a significant improvement for GIN and the SSDT exhibited the same
      for sustained attention, indicating learning generalization from an auditory
      sensory training to a top-down skill. For the other measures, all groups
      exhibited approximately the same level of gains, indicating the presence of a
      test-retest effect. Our findings also show that the memory span was not related
      to the learning generalization process given that the SSDT exhibited a more
      pronounced gain in attention skills after the sensory training.

PMID- 25597458
TI  - Continued maturation of the click-evoked auditory brainstem response in
      preschoolers.
AB  - BACKGROUND: Click-evoked auditory brainstem responses (ABRs) are a valuable tool
      for probing auditory system function and development. Although it has long been
      thought that the human auditory brainstem is fully mature by age 2 yr, recent
      evidence indicates a prolonged developmental trajectory. PURPOSE: The purpose of
      this study was to determine the time course of ABR maturation in a preschool
      population and fill a gap in the knowledge of development. RESEARCH DESIGN: Using
      a cross-sectional design, we investigated the effect of age on absolute
      latencies, interwave latencies, and amplitudes (waves I, III, V) of the click
      evoked ABR. STUDY SAMPLE: A total of 71 preschoolers (ages 3.12-4.99 yr)
      participated in the study. All had normal peripheral auditory function and IQ.
      DATA COLLECTION AND ANALYSIS: ABRs to a rarefaction click stimulus presented at
      31/sec and 80 dB SPL (73 dB nHL) were recorded monaurally using clinically
      standard recording and filtering procedures while the participant sat watching a
      movie. Absolute latencies, interwave latencies, and amplitudes were then
      correlated to age. RESULTS: Developmental changes were restricted to absolute
      latencies. Wave V latency decreased significantly with age, whereas wave I and
      III latencies remained stable, even in this restricted age range. CONCLUSIONS:
      The ABR does not remain static after age 2 yr, as seen by a systematic decrease
      in wave V latency between ages 3 and 5 yr. This finding suggests that the human
      brainstem has a continued developmental time course during the preschool years.
      Latency changes in the age 3-5 yr range should be considered when using ABRs as a
      metric of hearing health.

PMID- 25597459
TI  - The nature of communication throughout diagnosis and management planning in
      initial audiologic rehabilitation consultations.
AB  - BACKGROUND: Effective practitioner-patient communication throughout diagnosis and
      management planning positively influences patient outcomes. A patient-centered
      approach whereby patient involvement in decision making is facilitated, a
      therapeutic relationship is developed, and information is bilaterally exchanged
      in an appropriate manner, leads to improved patient satisfaction, adherence to
      treatment, and self-management. Despite this knowledge, little is known about the
      nature of audiologist-patient communication throughout diagnosis and management
      planning. PURPOSE: This research aimed to explore verbal communication between
      audiologists and patients/companions throughout diagnosis and management planning
      in initial audiology consultations. Specifically, this study aimed to describe
      the nature and dynamics of communication by examining the number, proportion, and
      type of verbal utterances by all speakers (audiologist, patient, and companion
      when present). In addition, this study aimed to investigate the influence of
      audiologist, patient, and consultation factors, such as verbal dominance, content
      balance, and communication control, on the dynamics of communication. STUDY
      SAMPLE: A total of 62 initial audiological rehabilitation consultations
      (involving 26 different audiologists) were filmed and analyzed using the Roter
      Interaction Analysis System. All patients were older than 55 yr, and a companion
      was present in 17 consultations. DATA COLLECTION AND ANALYSIS: This study focused
      solely on the communication relating to diagnosis and management planning
      (referred to as the "counseling phase"). Diagnosis, recommendations,
      rehabilitation options, and patient decisions were recorded along with the
      communication profiles and communication dynamics measured using the Roter
      Interaction Analysis System. Associations between communication dynamics (content
      balance, communication control, and verbal dominance) and eight variables were
      evaluated with Linear Mixed Model methods. RESULTS: The mean length of time for
      diagnosis and management planning was 29.0 min (range, 2.2-78.5 min).
      Communication profiles revealed that patient-centered communication was
      infrequently observed. First, opportunities to build a relationship were missed,
      such that patients' psychosocial concerns were rarely addressed and
      patients/companions showed little involvement in management planning. Second, the
      amount of talk was asymmetrical and the majority of audiologists' education and
      counseling utterances related to hearing aids; yet, only 56% of patients decided
      to obtain hearing aids at the conclusion of the consultation. Hearing aids were
      recommended in 83% of consultations where a hearing loss was diagnosed and
      alternative options were rarely provided. Thus, shared decision making rarely
      occurred, and audiologists often diagnosed a hearing loss and recommended hearing
      aids without patient involvement. In addition, when a greater proportion of time
      was dedicated to diagnosis and management planning, patients had greater input
      and control by asking more questions and requesting further information.
      CONCLUSIONS: Patient-centered communication was rarely observed in the 62
      consultations. Thus, although not measured in this study, patient outcomes are
      likely to be affected. Future research should examine the influence of
      audiologist communication on outcomes and encourage a shift toward patient
      centered audiological rehabilitation.

PMID- 25597460
TI  - Cochlear implant microphone location affects speech recognition in diffuse noise.
AB  - BACKGROUND: Despite improvements in cochlear implants (CIs), CI recipients
      continue to experience significant communicative difficulty in background noise.
      Many potential solutions have been proposed to help increase signal-to-noise
      ratio in noisy environments, including signal processing and external
      accessories. To date, however, the effect of microphone location on speech
      recognition in noise has focused primarily on hearing aid users. PURPOSE: The
      purpose of this study was to (1) measure physical output for the T-Mic as
      compared with the integrated behind-the-ear (BTE) processor mic for various
      source azimuths, and (2) to investigate the effect of CI processor mic location
      for speech recognition in semi-diffuse noise with speech originating from various
      source azimuths as encountered in everyday communicative environments. RESEARCH
      DESIGN: A repeated-measures, within-participant design was used to compare
      performance across listening conditions. STUDY SAMPLE: A total of 11 adults with
      Advanced Bionics CIs were recruited for this study. DATA COLLECTION AND ANALYSIS:
      Physical acoustic output was measured on a Knowles Experimental Mannequin for
      Acoustic Research (KEMAR) for the T-Mic and BTE mic, with broadband noise
      presented at 0 and 90 degrees  (directed toward the implant processor). In
      addition to physical acoustic measurements, we also assessed recognition of
      sentences constructed by researchers at Texas Instruments, the Massachusetts
      Institute of Technology, and the Stanford Research Institute (TIMIT sentences) at
      60 dBA for speech source azimuths of 0, 90, and 270 degrees . Sentences were
      presented in a semi-diffuse restaurant noise originating from the R-SPACE 8
      loudspeaker array. Signal-to-noise ratio was determined individually to achieve
      approximately 50% correct in the unilateral implanted listening condition with
      speech at 0 degrees . Performance was compared across the T-Mic, 50/50, and the
      integrated BTE processor mic. RESULTS: The integrated BTE mic provided
      approximately 5 dB attenuation from 1500-4500 Hz for signals presented at 0
      degrees  as compared with 90 degrees  (directed toward the processor). The T-Mic
      output was essentially equivalent for sources originating from 0 and 90 degrees .
      Mic location also significantly affected sentence recognition as a function of
      source azimuth, with the T-Mic yielding the highest performance for speech
      originating from 0 degrees . CONCLUSIONS: These results have clinical
      implications for (1) future implant processor design with respect to mic
      location, (2) mic settings for implant recipients, and (3) execution of advanced
      speech testing in the clinic.

PMID- 25597461
TI  - Test-retest reliability of the vestibular sensory-evoked potential (VsEP) in
      C57BL/6J mice.
AB  - BACKGROUND: The vestibular sensory-evoked potential (VsEP) is an electrical
      potential that provides a direct test of vestibular function in animals. VsEP
      recordings are carried out using subcutaneous stainless steel electrodes placed
      over the nuchal crest (noninverting), behind either the left or right pinna
      (inverting), and at the hip (ground). A noninvasive head clip is used to secure
      the head to a mechanical shaker for delivery of a linear vestibular stimulus
      measured in units of jerk (g/msec). Frequent repositioning of the noninvasive
      head clip and skin electrodes may be necessary during recording for particular
      protocols; however, the test-retest reliability of the VsEP response (latency,
      amplitude, and threshold) has not been determined. PURPOSE: The purpose of this
      study was to determine the possible effects of frequent repositioning of the
      noninvasive head clip and skin electrodes on VsEP response parameters (latencies,
      amplitudes, and thresholds). We hypothesize that the VsEP response will remain
      stable and reliable with such repeated measurements in a given animal across
      time. RESEARCH DESIGN: Linear VsEP responses were recorded from ten C57 mice
      (ages: 2.45 mo +/-0.20; weights: 17.94 g +/-1.51). Two standard threshold
      protocols and four repeated VsEP measurements at +6 dB re: 1.0 g/msec were
      performed, with four selected time points of head clip repositioning. In
      addition, three novice investigators performed measurements of noninverting
      electrode placement and head clip positioning. RESULTS: VsEP response latency,
      amplitude, and threshold means did not significantly change with frequent
      repositioning of the head clip and skin electrodes; however, increased
      variability was observed. CONCLUSIONS: The findings demonstrate that
      repositioning does not introduce significant changes in mean parameter values of
      the recorded VsEP response waveform; however, mean absolute difference
      calculations demonstrated that frequent repositioning increased response
      variance. For VsEP protocols requiring frequent repositioning, standardized
      electrode montage, optimal placement of the noninverting electrode at the nuchal
      crest, and increased sample size are suggested.

PMID- 25597462
TI  - A comparison of conventional and in-situ audiometry on participants with varying
      levels of sensorineural hearing loss.
AB  - BACKGROUND: In-situ audiometry is a hearing aid feature that enables the
      measurement of hearing threshold levels through the hearing instrument using the
      built-in sound generator and the hearing aid receiver. This feature can be used
      in hearing aid fittings instead of conventional pure-tone audiometry (PTA),
      particularly in places where no standard audiometric equipment is available.
      Differences between conventional and in-situ thresholds are described and
      discussed for some particular hearing aids. No previous investigation has
      measured and compared these differences for a number of current hearing aid
      models by various manufacturers across a wide range of hearing losses. PURPOSE:
      The purpose of this study was to perform a model-based comparison of
      conventionally and in-situ measured hearing thresholds. Data were collected for a
      range of hearing aid devices to study and generalize the effects that may occur
      under clinical conditions. RESEARCH DESIGN: Research design was an experimental
      and regression study. STUDY SAMPLE: A total of 30 adults with sensorineural
      hearing loss served as test persons. They were assigned to three subgroups of 10
      subjects with mild (M), moderate to severe (MS), and severe (S) sensorineural
      hearing loss. INTERVENTION: All 30 test persons underwent both conventional PTA
      and in-situ audiometry with four hearing aid models by various manufacturers.
      DATA COLLECTION AND ANALYSIS: The differences between conventionally and in-situ
      measured hearing threshold levels were calculated and evaluated by an exploratory
      data analysis followed by a sophisticated statistical modeling process. RESULTS:
      At 500 and 1500 Hz, almost all threshold differences (conventional PTA minus in
      situ data) were negative, i.e., in the low to mid frequencies, hearing loss was
      overestimated by most devices relative to PTA. At 4000 Hz, the majority of
      differences (7 of 12) were positive, i.e., in the frequency range above 1500 Hz,
      hearing loss was frequently underestimated. As hearing loss increased (M->MS->S),
      the effect of the underestimation decreased. At 500 and 1500 Hz, Resound devices
      showed the smallest threshold deviations, followed by Phonak, Starkey, and Oticon
      instruments. At 4000 Hz, this observed pattern partly disappeared and Starkey and
      Oticon devices showed a reversed effect with increasing hearing loss (M->MS->S).
      Because of high standard errors for the estimates, only a few explicit rankings
      of the devices could be established based on significant threshold differences
      (5% level). CONCLUSIONS: Differences between conventional PTA and in-situ
      threshold levels may be attributed to (1) frequency, (2) device/hearing loss, and
      (3) calibration/manufacturer effects. Frequency effects primarily resulting in an
      overestimation of hearing loss by in-situ audiometry in the low and mid
      frequencies are mainly due to sound drain-off through vents and leaks.
      Device/hearing loss effects may be due to leakage as well as boundary effects
      because in-situ audiometry is confined to a limited measurement range. Finally,
      different calibration approaches may result in different offset levels between
      PTA and in-situ audiometry calibration. In some cases, the observed threshold
      differences of up to 10-15 dB may translate to varied hearing aid fittings for
      the same user depending on how hearing threshold levels were measured.

PMID- 25597463
TI  - Effects of coordinated compression and pinna compensation features on horizontal
      localization performance in hearing aid users.
AB  - BACKGROUND: Hearing-impaired listeners localize sounds better unaided than aided.
      Wide dynamic range compression circuits operating independently at each ear in
      bilateral fittings, and microphone positions of different hearing aid styles,
      have been cited as a reason. Two hearing aid features, inter-ear coordinated
      compression (IE) and pinna compensation (PC), were developed to mitigate the
      compromised aided localization performance. PURPOSE: This study examined the
      effect of IE and PC on aided localization performance in the horizontal plane
      with hearing-impaired listeners. RESEARCH DESIGN: A single-blind, repeated
      measures design was used. STUDY SAMPLE: A total of 10 experienced hearing aid
      users with bilaterally symmetrical sensorineural hearing loss who had previously
      participated in localization training were evaluated. DATA COLLECTION AND
      ANALYSIS: Localization performance was measured using 12 loudspeakers spaced 30
      degrees  apart on the horizontal plane. Aided performance was evaluated using a
      behind-the-ear hearing aid at four settings: omnidirectional microphone (Omni),
      Omni microphone with the PC feature, Omni microphone with IE, and Omni microphone
      with the PC feature and IE together. In addition, unaided localization
      performance was measured. RESULTS: Significant improvement in the localization
      accuracy was measured for sounds arriving from the back when comparing the PC
      with the Omni conditions. The use of IE reduced the magnitude of errors for some
      listeners for sounds originating from +/-90 degrees . The average reduction in
      the errors was 7.3 degrees . CONCLUSIONS: This study confirmed that the use of
      the PC feature improved localization for sounds arriving from behind the
      listener. The use of IE may improve localization for some listeners for sounds
      arriving from the sides.

PMID- 25597464
TI  - Evaluation of the benefits of binaural hearing on the telephone for children with
      hearing loss.
AB  - BACKGROUND: There is a paucity of published studies examining how children with
      hearing loss understand speech over the telephone. Previous studies on adults
      with hearing aids have suggested that adults with bilateral hearing aids
      experience significant difficulty recognizing speech on the telephone when
      listening with one ear, but the provision of telephone input to both ears
      substantially improved speech understanding. PURPOSE: The objectives of this
      study were to measure speech recognition in quiet and in noise for a group of
      older children with hearing loss over the telephone and to evaluate the effects
      of binaural hearing (e.g., DuoPhone) on speech recognition over the telephone.
      RESEARCH DESIGN: A cross-sectional, repeated-measures design was used in this
      study. STUDY SAMPLE: A total of 14 children, ages 6-14 yr, participated in the
      study. Participants were obtained using convenience sampling from a nonprofit
      clinic population. INTERVENTION: Speech recognition in quiet and in noise with
      binaural versus monaural telephone input was compared in pediatric participants.
      DATA COLLECTION AND ANALYSIS: Monosyllabic word recognition was assessed in quiet
      and classroom noise set at 50 dBA in conditions with monaural and binaural
      (DuoPhone) telephone input. RESULTS: The children's speech recognition in quiet
      and in noise was significantly better with binaural telephone input relative to
      monaural telephone input. CONCLUSIONS: To obtain optimal performance on the
      telephone, the following considerations may apply: (1) use of amplification with
      binaural streaming capabilities (e.g., DuoPhone), (2) counseling of family and
      children on how to best use the telephone, (3) provision of telecoil with
      microphone attenuation for improved signal-to-noise ratio, and (4) use of probe
      tube measures to verify the appropriateness of the telephone programs.

PMID- 25597465
TI  - Air conduction, bone conduction, and soft tissue conduction audiograms in normal
      hearing and simulated hearing losses.
AB  - BACKGROUND: In order to differentiate between a conductive hearing loss (CHL) and
      a sensorineural hearing loss (SNHL) in the hearing-impaired individual, we
      compared thresholds to air conduction (AC) and bone conduction (BC) auditory
      stimulation. The presence of a gap between these thresholds (an air-bone gap) is
      taken as a sign of a CHL, whereas similar threshold elevations reflect an SNHL.
      This is based on the assumption that BC stimulation directly excites the inner
      ear, bypassing the middle ear. However, several of the classic mechanisms of BC
      stimulation such as ossicular chain inertia and the occlusion effect involve
      middle ear structures. An additional mode of auditory stimulation, called soft
      tissue conduction (STC; also called nonosseous BC) has been demonstrated, in
      which the clinical bone vibrator elicits hearing when it is applied to soft
      tissue sites on the head, neck, and thorax. PURPOSE: The purpose of this study
      was to assess the relative contributions of threshold determinations to
      stimulation by STC, in addition to AC and osseous BC, to the differential
      diagnosis between a CHL and an SNHL. RESEARCH DESIGN: Baseline auditory
      thresholds were determined in normal participants to AC (supra-aural earphones),
      BC (B71 bone vibrator at the mastoid, with 5 N application force), and STC (B71
      bone vibrator) to the submental area and to the submandibular triangle with 5 N
      application force) stimulation in response to 0.5, 1.0, 2.0, and 4.0 kHz tones. A
      CHL was then simulated in the participants by means of an ear plug. Separately,
      an SNHL was simulated in these participants with 30 dB effective masking. STUDY
      SAMPLE: STUDY SAMPLE consisted of 10 normal-hearing participants (4 males; 6
      females, aged 20-30 yr). DATA COLLECTION AND ANALYSIS: AC, BC, and STC thresholds
      were determined in the initial normal state and in the presence of each of the
      simulations. RESULTS: The earplug-induced CHL simulation led to a mean AC
      threshold elevation of 21-37 dB (depending on frequency), but not of BC and STC
      thresholds. The masking-induced SNHL led to a mean elevation of AC, BC, and STC
      thresholds (23-36 dB, depending on frequency). In each type of simulation, the BC
      threshold shift was similar to that of the STC threshold shift. CONCLUSIONS:
      These results, which show a similar threshold shift for STC and for BC as a
      result of these simulations, together with additional clinical and laboratory
      findings, provide evidence that BC thresholds likely represent the threshold of
      the nonosseous BC (STC) component of multicomponent BC at the BC stimulation
      site, and thereby succeed in clinical practice to contribute to the differential
      diagnosis. This also provides evidence that STC (nonosseous BC) stimulation at
      low intensities probably does not involve components of the middle ear,
      represents true cochlear function, and therefore can also contribute to a
      differential diagnosis (e.g., in situations where the clinical bone vibrator
      cannot be applied to the mastoid or forehead with a 5 N force, such as in severe
      skull fracture).

PMID- 25597467
TI  - Photochemistry of N-(selenoalkyl)-phthalimides. Formation of N, Se-heterocyclic
      systems.
AB  - A variety of N-(selenomethyl)alkyl-phthalimides (alkyl = -(CH2)n-; n = 2-5, 1a,
      b, d, e) and N-(selenobenzyl)propyl phthalimide (1c) were synthesized and their
      photochemistry was studied at lambda = 300 nm. Steady-state photolysis and laser
      time-resolved spectroscopy studies confirmed that these reactions proceeded by
      direct or acetone-sensitized excitation followed by intramolecular electron
      transfer (ET) between Se atom and the phthalimide moiety. Two main pathways are
      possible after ET: proton transfer to the ketyl radical anion from the CH3Se(+)
      or the -CH2Se(+)- moieties, yielding the corresponding biradicals. Collapse of
      these biradicals yields cyclization products with the respective endo or exo
      selenium-containing heterocycles. Competition between both proton transfer
      processes depends on the chain length of the alkyl spacer between the phthalimide
      and Se groups as well as the size of the cycle being formed.

PMID- 25597468
TI  - Painful and petechial rash after injecting black tar heroin.
AB  - A painful petechial rash developed in a patient after the subcutaneous or
      intravenous injection of reported black tar heroin. Additional history and the
      appearance of the skin lesion suggested otherwise.

PMID- 25597469
TI  - Iso-selective ring-opening polymerization of rac-lactide catalyzed by crown ether
      complexes of sodium and potassium naphthalenolates.
AB  - Two crown ether complexes of sodium and potassium naphthalenolates were
      synthesized and entirely characterized. The two complexes can iso-selectively
      catalyze the ring-opening polymerization (ROP) of rac-lactide at room temperature
      and afford polylactides with desired molecular weights and narrow PDIs; the best
      isotacticity (Pm) achieved was 0.73. 

PMID- 25597471
TI  - Dual functional graphene derivative-based electrochemical platforms for detection
      of the TP53 gene with single nucleotide polymorphism selectivity in biological
      samples.
AB  - Novel disposable electrochemical DNA sensors were prepared for the detection of a
      target DNA sequence on the p53 tumor suppressor (TP53) gene. The electrochemical
      platform consisted of screen-printed carbon electrodes (SPCEs) functionalized
      with a water-soluble reduced graphene oxide-carboxymethylcellulose (rGO-CMC)
      hybrid nanomaterial. Two different configurations involving hairpin specific
      capture probes of different length covalently immobilized through carbodiimide
      chemistry on the surface of rGO-CMC-modified SPCEs were implemented and compared.
      Upon hybridization, a streptavidin-peroxidase (Strep-HRP) conjugate was employed
      as an electrochemical indicator. Hybridization was monitored by recording the
      amperometric responses measured at -0.10 V (vs an Ag pseudo-reference electrode)
      upon the addition of 3,3',5,5'-tetramethylbenzidine (TMB) as a redox mediator and
      H2O2 as an enzyme substrate. The implemented DNA platforms allow single
      nucleotide polymorphism (SNP) discrimination in cDNAs from human breast cancer
      cell lines, which makes such platforms excellent as new diagnosis tools in
      clinical analysis. 

PMID- 25597472
TI  - Genetic association between Interleukin-17A gene polymorphisms and the
      pathogenesis of Graves' disease in the Han Chinese population.
AB  - OBJECTIVE: Graves' disease, one of the commonest autoimmune disorders, has a
      complex genetic basis. Interleukin-17A (IL-17A) is an important cytokine involved
      in innate and adaptive immune responses. This case-control study sought to
      investigate genetic association between the IL-17A gene and the process of
      Graves' disease (GD). DESIGN AND METHODS: Our pilot study was performed on a
      cohort from Shanghai, which included 713 patients with GD and 756 healthy
      controls. A replicate cohort was from Xiamen, recruiting 444 patients with GD and
      427 healthy subjects. Six single nucleotide polymorphisms (SNPs) (rs4711998,
      rs3819024, rs2275913, rs8193037, rs3819025 and rs3748067) within the IL-17A gene
      were genotyped by the SNPstream Genotyping Systems and Taqman PCR method.
      RESULTS: In Shanghai cohorts, the frequencies of rs8193037 alleles were strongly
      different between patients with Graves' disease (G, 87.6% and A, 12.4%) and
      healthy controls (G, 91.4% and A, 8.6%) (P = 0.00067). The A carriers were
      associated with increased Graves' disease risks when compared with the G carriers
      (OR = 1.51, 95%CI = 1.19-1.92). In replicate cohorts, the proportion of
      individuals carrying the A allele of rs8193037 was significantly higher in
      patients with Graves' disease than in controls [Graves' disease vs control, 14.3%
      vs 9.1%, OR = 1.66 (95% CI: 1.23-2.24), Pallele  = 0.0082]. In addition,
      rs8193037 and rs3748067 were found to be different in both genotype and allele
      distributions in Graves' disease-associated ophthalmopathy patients and controls
      in Shanghai cohorts. Haplotype association analysis also identified five main
      haplotypes of those six SNPs. CONCLUSION: These results suggested that the
      polymorphism of IL-17A rs8193037 was strongly associated with Graves' disease
      susceptibility in the Chinese Han population.z.

PMID- 25597473
TI  - Association between serum lipids and membrane fatty acids and clinical
      characteristics in patients with schizophrenia.
AB  - OBJECTIVE: Earlier reports indicate that patients with schizophrenia have altered
      lipid levels in serum and cell membranes. The purpose of this study was to
      determine the relationship between clinical characteristics and serum and
      membrane lipids. METHOD: Fifty-five patients with schizophrenia and 51 healthy
      controls were included. The patients were characterized with Positive and
      Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF). Serum
      lipids [high- and low-density lipoprotein cholesterol (HDL, LDL) and triglyceride
      (TG)] and erythrocyte polyunsaturated fatty acids (PUFA) were measured. RESULTS:
      Among the participants with schizophrenia, there was a significant correlation
      between serum triglyceride levels and PANSS-positive symptoms (r = 0.28, P =
      0.04), GAF-S (r = -0.48, P = 0.001) and GAF-F (r = -0.32, P = 0.01), and between
      HDL level and GAF-S (r = 0.37, P = 0.008) and GAF-F (r = 0.28, P = 0.04). Long
      chain PUFA were significantly associated with PANSS-negative symptoms (r = 0.52,
      P < 0.001), GAF-S (r = -0.32, P = 0.02), and GAF-F (r = -0.29, P = 0.04). The
      patients with schizophrenia had significantly higher TG (P < 0.001) and lower HDL
      (P < 0.001) levels than healthy controls. HDL was also lower in the subgroup (n =
      11) not receiving antipsychotic medication (P = 0.02). CONCLUSION: The results
      suggest associations between lipid profile and clinical characteristics. This may
      indicate a role for lipid biology in schizophrenia pathophysiology.

PMID- 25597474
TI  - Serum total oxidant and antioxidant status in earthquake survivors with post
      traumatic stress disorder.
AB  - OBJECTIVE: Oxidative stress has been shown to play an important role in the
      pathogenesis of post-traumatic stress disorder (PTSD). Although there are some
      studies on oxidative stress and PTSD, there is no report available on the serum
      total oxidant and antioxidant status in earthquake survivors with PTSD.
      Therefore, this study aimed to investigate the serum total oxidant and
      antioxidant status in earthquake survivors with chronic PTSD. MATERIAL AND
      METHODS: The study group included 45 earthquake survivors with PTSD and 40
      earthquake survivors without PTSD. The oxidative status was determined using the
      total antioxidant status and total oxidant status (TOS) measurements and by
      calculating the oxidative stress index (OSI). RESULTS: There were no
      statistically significant differences in the total antioxidant status, TOS, or
      OSI when comparing individuals with and without PTSD (all, p>0.05). There were no
      correlations between Clinician-Administered PTSD Scale scores and oxidant and
      antioxidant stress markers (all, p>0.05). CONCLUSIONS: Our results suggest that
      the total oxidant and antioxidant status may not affect earthquake survivors with
      PTSD. This is the first study to evaluate the oxidative status in earthquake
      survivors with PTSD. Further studies are necessary to confirm these findings.

PMID- 25597476
TI  - Alantolactone Induces Apoptosis and Cell Cycle Arrest on Lung Squamous Cancer SK
      MES-1 Cells.
AB  - Alantolactone, a sesquiterpene lactone compound, has variety of pharmacological
      properties, including anti-inflammatory and antineoplastic effects. In our study,
      alantolactone inhibited cancer cell proliferation. To explore the mechanisms
      underlying its antitumor action, we further examined apoptotic cells and cell
      cycle distribution using flow cytometry analysis. Alantolactone triggered
      apoptosis and induced cell cycle G1/G0 phase arrest. Furthermore, the expressions
      of caspases-8, -9, -3, PARP, and Bax were significantly upregulated, while
      antiapoptotic factor Bcl-2 expression was inhibited. In addition, the expressions
      of cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D3, and cyclin D1 were
      downregulated by alantolactone. Therefore, our findings indicated that
      alantolactone has an antiproliferative role on lung squamous cancer cells, and it
      may be a promising chemotherapeutic agent for squamous lung cancer SK-MES-1
      cells. 

PMID- 25597477
TI  - Species survival emerge from rare events of individual migration.
AB  - Ecosystems greatly vary in their species composition and interactions, yet they
      all show remarkable resilience to external influences. Recent experiments have
      highlighted the significant effects of spatial structure and connectivity on the
      extinction and survival of species. It has also been emphasized lately that in
      order to study extinction dynamics reliably, it is essential to incorporate
      stochasticity, and in particular the discrete nature of populations, into the
      model. Accordingly, we applied a bottom-up modeling approach that includes both
      spatial features and stochastic interactions to study survival mechanisms of
      species. Using the simplest spatial extension of the Lotka-Volterra predator-prey
      model with competition, subject to demographic and environmental noise, we were
      able to systematically study emergent properties of this rich system. By scanning
      the relevant parameter space, we show that both survival and extinction processes
      often result from a combination of habitat fragmentation and individual rare
      events of recolonization. 

PMID- 25597475
TI  - CW-EPR studies revealed different motional properties and oligomeric states of
      the integrin beta1a transmembrane domain in detergent micelles or liposomes.
AB  - Integrins are heterodimeric membrane proteins that regulate essential processes:
      cell migration, cell growth, extracellular matrix assembly and tumor metastasis.
      Each integrin alpha or beta subunit contains a large extracellular domain, a
      single transmembrane (TM) domain, and a short cytoplasmic tail. The integrin TM
      domains are important for heterodimeric association and dissociation during the
      conversion from inactive to active states. Moreover, integrin clustering occurs
      by homo-oligomeric interactions between the TM helices. Here, the transmembrane
      and cytoplasmic (TMC) domains of integrin beta1a were overexpressed, and the
      protein was purified in detergent micelles and/or reconstituted in liposomes. To
      investigate the TM domain conformational properties of integrin beta1a, 26
      consecutive single cysteine mutants were generated for site-directed spin
      labeling and continuous-wave electron paramagnetic resonance (CW-EPR) mobility
      and accessibility analyses. The mobility analysis identified two integrin beta1a
      TM regions with different motional properties in micelles and a non-continuous
      integrin beta1a-TM helix with high immobility in liposomes. The accessibility
      analysis verified the TM range (Val737-Lys752) of the integrin beta1a-TMC in
      micelles. Further mobility and accessibility comparisons of the integrin beta1a
      TMC domains in micelles or liposomes identified distinctively different
      oligomeric states of integrin beta1a-TM, namely a monomer embedded in detergent
      micelles and leucine-zipper-like homo-oligomeric clusters in liposomes. 

PMID- 25597478
TI  - Comparison of the overactive bladder symptom score and the overactive bladder
      symptom score derived from the bladder diaries.
AB  - AIMS: The overactive bladder symptom score (OABSS) is a useful tool for assessing
      the four key symptoms of overactive bladder (OAB), but it sometimes misrepresents
      a patient's actual voiding status. To examine whether the patient-determined
      OABSS underestimates or overestimates the true status, its results were compared
      to those of the OABSS derived from a 7-day bladder diary (OABSS-BD). METHODS:
      Records of patients who visited our outpatient clinic with lower urinary tract
      symptoms were evaluated retrospectively. The patients were asked to complete the
      OABSS and the 7-day bladder diary (BD). The OABSS-BD was created from the 7-day
      BD. Questions were compared between the OABSS and the OABSS-BD. RESULTS: A total
      of 44 men and 31 women were evaluated. For daytime frequency, the mean OABSS
      score was 1.03 +/- 0.57 and the OABSS-BD score was 0.69 +/- 0.52 (P < 0.01). For
      nighttime frequency, the mean OABSS score was 2.27 +/- 0.84, and the OABSS-BD
      score was 1.96 +/- 1.00 (P = 0.04). For urinary urgency, the mean OABSS score was
      2.49 +/- 1.83, and the OABSS-BD score was 2.70 +/- 1.90 (P = 0.27). For urgency
      incontinence, the mean OABSS score was 1.67 +/- 1.92, and the OABSS-BD score was
      1.52 +/- 1.87 (P = 0.28). For the total score, the mean OABSS total score was
      7.26 +/- 3.92, and the OABSS-BD score was 6.98 +/- 3.26 (P = 0.23). CONCLUSIONS:
      The OABSS is a very simple and useful tool. However, compared to the results from
      the 7-day FVC, the present patients overestimated daytime and nighttime
      frequency.

PMID- 25597480
TI  - A self-assembled superhydrophobic electrospun carbon-silica nanofiber sponge for
      selective removal and recovery of oils and organic solvents.
AB  - An oil spill needs timely cleanup before it spreads and poses serious
      environmental threat to the polluted area. This always requires the cleanup
      techniques to be efficient and cost-effective. In this work, a lightweight and
      compressible sponge made of carbon-silica nanofibers is derived from
      electrospinning nanotechnology that is low-cost, versatile, and readily scalable.
      The fabricated sponge has high porosity (>99 %) and displays ultra-hydrophobicity
      and superoleophilicity, thus making it a suitable material as an oil adsorbent.
      Owing to its high porosity and low density, the sponge is capable of adsorbing
      oil up to 140 times its own weight with its sorption rate showing solution
      viscosity dependence. Furthermore, sponge regeneration and oil recovery are
      feasible by using either cyclic distillation or mechanical squeezing. 

PMID- 25597479
TI  - Going outdoors and cognitive function among community-dwelling older adults:
      Moderating role of physical function.
AB  - AIMS: Identifying the risk factors of cognitive impairment is essential for
      implementing effective prevention strategies for dementia. Previous studies have
      shown that the frequency of going outdoors is inversely associated with cognitive
      decline. Little research has examined whether the relationship between going
      outdoors and cognitive decline varies with physical functioning in older adults.
      The aim of the present study was to examine the relationship between going
      outdoors and cognitive function in older adults with and without physical
      function limitations. METHODS: The present study analyzed the data of 4450
      individuals (aged 65 years or older) who participated in the Obu Study of Health
      Promotion for the Elderly. The measures were the Mini-Mental State Examination
      (MMSE), going outdoors (at least once a week or not), self-reported physical
      function limitations (with or without), and demographic and health-related
      factors as potential confounders. RESULTS: Analysis of covariance and post-hoc
      comparisons showed that although going outdoors at least once a week was
      associated with higher MMSE scores among older adults with limited physical
      function, it was not significantly associated with the MMSE scores among older
      adults without limited physical function. Similarly, logistic regression
      analyses, stratified by physical function, showed a significant association
      between going outdoors and MMSE (<24 points or not) among older adults with
      limited physical function. CONCLUSIONS: The results show that going outdoors less
      than once a week is associated with decreased cognitive function among older
      adults with limited physical function, but it is not associated with cognitive
      function among older adults without limited physical function.

PMID- 25597481
TI  - GJIC Enhances the phototoxicity of photofrin-mediated photodynamic treatment by
      the mechanisms related with ROS and Calcium pathways.
AB  - Despite initially positive responses, recurrences after Photodynamic treatment
      (PDT) can occur and there is need for improvement in the effectiveness of PDT.
      Our study uniquely showed that there was a significantly gap junctional
      intercellular communication (GJIC)-dependent PDT cytotoxicity. The presence of
      GJIC composed of Connexin 32 increased the PDT phototoxicity in transfected HeLa
      cells and in the xenograft tumors, and the enhanced phototoxicity of Photofrin
      mediated PDT by GJIC was related with ROS and calcium pathways. Our study
      indicates the possibility that up-regulation or maintenance of gap junction
      functionality may be used to increase the efficacy of PDT. The phototoxicity
      effect of Photofrin was substantially greater in Dox-treated cells, which
      expressed the Cx32 and formed the GJ, than Dox-untreated. 

PMID- 25597483
TI  - COX-2 regulation and TUNEL-positive cell death differ between genders in the
      secondary inflammatory response following experimental penetrating focal brain
      injury in rats.
AB  - INTRODUCTION: Traumatic brain injury is followed by secondary neuronal
      degeneration, largely dependent on an inflammatory response. This response is
      probably gender specific, since females are better protected than males in
      experimental models. The reasons are not fully known. We examined aspects of the
      inflammatory response following experimental TBI in male and female rats to
      explore possible gender differences at 24 h and 72 h after trauma, times of peak
      histological inflammation and neuronal degeneration. METHODS: A penetrating brain
      injury model was used to produce penetrating focal TBI in 20 Sprague-Dawley rats,
      5 males and 5 females for each time point. After 24 and 72 h the brains were
      removed and subjected to in situ hybridization and immunohistochemical analyses
      for COX-2, iNOS, osteopontin, glial fibrillary acidic protein, 3-nitrotyrosine,
      TUNEL and Fluoro-Jade. RESULTS: COX-2 mRNA and protein levels were increased in
      the perilesional area compared to the uninjured contralateral side and
      significantly higher in males at 24 h and 72 h (p < 0.05). iNOS mRNA was
      significantly increased in females at 24 h (p < 0.05) although protein was not.
      TUNEL was increased in male rats after 24 h (p < 0.05). Glial fibrillary acidic
      protein, osteopontin, 3-nitrotyrosine and Fluoro-Jade stained degenerating
      neurons were increased in the perilesional area, showing no difference between
      genders. CONCLUSIONS: COX-2 regulation differed between genders after TBI. The
      increased COX-2 expression in male rats correlated with increased apoptotic cell
      death detected by increased TUNEL staining at 24 h, but not with neuronal
      necrosis measured by Flouro-Jade. Astrogliosis and microgliosis did not differ,
      confirming a comparable level of trauma. The gender-specific trait of the
      secondary inflammatory response may be connected to prostaglandin regulation,
      which may partially explain gender variances in outcome after TBI.

PMID- 25597482
TI  - Over-expression of miR-10b in NPC patients: correlation with LMP1 and Twist1.
AB  - Aberrant expression of miR-10b has been described in many cancers but remains
      unexplored in nasopharyngeal carcinoma (NPC). Therefore, we aimed to study the
      miR-10b expression level in 43 NPC biopsies collected from Tunisian patients and
      three NPC xenografts. Then, we investigated the correlation between miR-10b
      expression and its upstream regulators LMP1/Twist1 as well as its adjacent gene
      HoxD4. We showed that miR-10b was significantly up-regulated in NPC biopsies
      compared to non-tumor nasopharyngeal tissues (fold change 153; p = 0.004) and
      associated with advanced clinical stage and young age at diagnosis (p = 0.005 and
      p = 0.011, respectively). In addition, over-expression of miR-10b was positively
      associated with the transcription factor Twist1 as well as the EBV oncoprotein
      LMP1 (fold change 6.32; p = 0.014, fold change 6.58; p = 0.01 respectively).
      Furthermore, higher level of miR-10b was observed in tumors with simultaneous
      expression of LMP1 and Twist1, compared to those expressing only Twist1 (fold
      change 2.49; p = 0.033). Meanwhile, the analysis of the link between miR-10b and
      its neighbor gene HoxD4 did not show any significant correlation (Fisher test p =
      0.205; Mann-Whitney test p = 0.676). This study reports the first evidence of miR
      10b over-expression in NPC patients. Furthermore, our findings can support hsa
      miR-10b gene regulation through LMP1/Twist1 in NPC malignancy.

PMID- 25597484
TI  - Bilateral hemifacial spasm might be cured by unilateral microvascular
      decompression.

PMID- 25597485
TI  - Thrombin hemostatic matrix leading to acute cerebral edema and sterile fluid
      collection formation post-tumor resection: two cases.

PMID- 25597486
TI  - Loss of MyD88 leads to more aggressive TRAMP prostate cancer and influences tumor
      infiltrating lymphocytes.
AB  - BACKGROUND: The influence of pattern recognition receptor (PRR) signaling in the
      prostate tumor microenvironment remains unclear. Although there may be a role for
      PRR agonists as adjuvants to therapy, prior evidence suggests tumor promoting as
      well as tumor inhibiting mechanisms. The purpose of this study is to examine the
      role of the key Toll-like receptor (TLR) signaling adaptor protein myeloid
      differentiation primary response gene 88 (MyD88) in prostate cancer development.
      METHODS: MyD88(-/-) mice in a C57Bl6 background were crossed with transgenic
      adenocarcinomas of the mouse prostate (TRAMP) mice to create MyD88(-/-)
      TRAMP(Tg+/-) animals, which were compared to MyD88(+/+) TRAMP(Tg+/-) animals and
      their non-transgenic counterparts at 30 weeks. Prostates were examined
      histologically, by immunohistochemistry and immunofluorescence staining, and by
      qPCR, to characterize tumor-infiltrating immune populations as well as activation
      of the downstream NF-kappaB pathway and androgen receptor (AR) expression.
      Splenocytes were examined for development of distinct immune cell populations.
      RESULTS: Absence of MyD88 led to increased prostatic intraepithelial neoplasm
      (PIN) and areas of well-differentiated adenocarcinoma in TRAMP transgenic mice.
      Analysis of infiltrating immune populations revealed an increase in CD11b(+)
      Gr1(+) myeloid-derived suppressor cells (MDSCs), as evidenced by increased
      expression of prostatic arginase-1 and iNOS as well as the cytokine IL-10, and a
      deficiency in NK cells in prostates from MyD88(-/-) TRAMP(Tg+/-) compared to
      MyD88(+/+) TRAMP(Tg+/-) mice, whereas a decrease in splenocytic NK cell
      differentiation was observed in MyD88(-/-) mice. Prostate tumors revealed no
      significant differences in NF-kappaB or AR expression in MyD88(+/+) TRAMP(Tg+/-)
      compared to MyD88(-/-) TRAMP(Tg+/-) mice. CONCLUSIONS: During prostate cancer
      development in the TRAMP model, MyD88 may play a role in limiting prostate
      tumorigenesis by altering tumor-infiltrating immune populations. This suggests
      that in the context of specific cancers, distinct PRRs and signaling pathways of
      innate immune signaling may influence the tumor microenvironment and represent a
      novel therapeutic strategy.

PMID- 25597487
TI  - Upper extremity 3-dimensional reachable workspace analysis in dystrophinopathy
      using Kinect.
AB  - INTRODUCTION: An innovative upper extremity 3-dimensional (3D) reachable
      workspace outcome measure acquired using the Kinect sensor is applied toward
      Duchenne/Becker muscular dystrophy (DMD/BMD). The validity, sensitivity, and
      clinical meaningfulness of this novel outcome measure are examined. METHODS:
      Upper extremity function assessment (Brooke scale and NeuroQOL questionnaire) and
      Kinect-based reachable workspace analyses were conducted in 43 individuals with
      dystrophinopathy (30 DMD and 13 BMD, aged 7-60 years) and 46 controls (aged 6-68
      years). RESULTS: The reachable workspace measure reliably captured a wide range
      of upper extremity impairments encountered in both pediatric and adult, as well
      as ambulatory and non-ambulatory individuals with dystrophinopathy. Reduced
      reachable workspaces were noted for the dystrophinopathy cohort compared with
      controls, and they correlated with Brooke grades. In addition, progressive
      reduction in reachable workspace correlated directly with worsening ability to
      perform activities of daily living, as self-reported on the NeuroQOL. CONCLUSION:
      This study demonstrates the utility and potential of the novel sensor-acquired
      reachable workspace outcome measure in dystrophinopathy.

PMID- 25597488
TI  - Bio-relevant cobalt(II) complexes with compartmental polyquinoline ligand:
      synthesis, crystal structures and biological activities.
AB  - Three new Co(II) complexes, [Co4(L)2(MU3-CrO4)2](ClO4)2.2CH3CN (1), [Co2(L)(MU2
      na)(H2O)](ClO4)2 (2) and [Co2(L)(MU2-ba)](ClO4)2.0.5CH3CN (3) (Hna=nicotinic
      acid, Hba=benzoic acid, HL=N,N,N',N'-tetrakis (2-quinolylmethyl)-1,3
      diaminopropan-2-ol), have been synthesized and characterized by various
      physicochemical techniques. The Co(II) centers are connected by endogenous alkoxy
      bridge from L(-) and various extrinsic auxiliary linkers, some of which display
      coordination number asymmetry (5, 6-coordinated for 1 and 2; 5, 5-coordinated for
      3). It is worth mentioning that complex 1 contains two rare reported MU3-eta(1),
      eta(1), eta(1)-CrO4(2-) moieties. Susceptibility data of three complexes
      indicated intramolecular antiferromagnetic coupling of high-spin Co(II) atoms
      with exchange integral values (J) -14.94 cm(-1), -11.26 cm(-1) and -13.66 cm(-1)
      for 1, 2 and 3, respectively. Interaction of compounds with calf thymus DNA (CT
      DNA) have been investigated by absorption spectral titration, ethidium bromide
      (EB) displacement assay and viscosity measurement, which revealed that compounds
      bound to CT-DNA with a moderate intercalative mode, accompanied the affinities
      order: 1>2~3. Three complexes exhibit oxidative cleavage of pBR322 plasmid DNA
      including a reliance on H2O2 as the activator. Compound 1 demonstrates an
      increased DNA cleavage activity as compared with 2 and 3, which could degrade
      super coiled DNA (SC DNA) into nicked coiled DNA (NC DNA) in lower concentration
      (5 MUM). Moreover, all compounds could quench the intrinsic fluorescence of
      bovine serum albumin (BSA) in a static quenching process. Complex 1 also shows
      higher anticancer activity than cisplatin with lower IC50 value of incubation for
      both 24 h and 48 h.

PMID- 25597491
TI  - Professor Tetsuo Nozoe and Taiwan.

PMID- 25597489
TI  - Design-based inference in time-location sampling.
AB  - Time-location sampling (TLS), also called time-space sampling or venue-based
      sampling is a sampling technique widely used in populations at high risk of
      infectious diseases. The principle is to reach individuals in places and at times
      where they gather. For example, men who have sex with men meet in gay venues at
      certain times of the day, and homeless people or drug users come together to take
      advantage of services provided to them (accommodation, care, meals). The
      statistical analysis of data coming from TLS surveys has been comprehensively
      discussed in the literature. Two issues of particular importance are the
      inclusion or not of sampling weights and how to deal with the frequency of venue
      attendance (FVA) of individuals during the course of the survey. The objective of
      this article is to present TLS in the context of sampling theory, to calculate
      sampling weights and to propose design-based inference taking into account the
      FVA. The properties of an estimator ignoring the FVA and of the design-based
      estimator are assessed and contrasted both through a simulation study and using
      real data from a recent cross-sectional survey conducted in France among drug
      users. We show that the estimators of prevalence or a total can be strongly
      biased if the FVA is ignored, while the design-based estimator taking FVA into
      account is unbiased even when declarative errors occur in the FVA. 

PMID- 25597490
TI  - Rational expectations? An explorative study of subjective survival probabilities
      and lifestyle across Europe.
AB  - BACKGROUND: Subjective survival probabilities (SSPs) are considered relevant in
      relation to lifestyle as lifestyle improvements may improve health and lower
      mortality risk. OBJECTIVE: To study individuals' SSP in a population of elderly
      (i.e. 60 years and older) from 15 European countries. METHODS: Data from the
      second wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) were
      used. Individuals were asked about their chances to live up to age [T] or more.
      These SSPs were related to general characteristics, health and lifestyle. In
      addition, cross-country comparisons were made. The validity of the probabilistic
      elicitation format used for collecting SSPs was also addressed. RESULTS: The
      average subjective probability of surviving the next 9-15 years was around 57%.
      Mean SSPs varied significantly across age, with lower means at higher ages. Cross
      country comparisons showed lowest mean in the Czech Republic (42%) and the
      highest in Denmark (64%). SSPs correlated with socio-demographic, socio-economic
      and also strongly with (objective) health characteristics except for obesity.
      Smokers reported significantly lower SSPs compared to non-smokers, but no
      difference was found between non-smokers and quitters. Excessive alcohol
      consumers reported significantly higher SSPs than moderate consumers and
      abstainers, but this only held for female excessive drinkers. Physical inactivity
      was negatively associated with SSPs, but this relation was attenuated at higher
      ages. In this context, important cross-country differences were found.
      CONCLUSIONS: Subjective survival probabilities are informative and relevant in
      relation to lifestyle decisions and can be validly obtained in elder people. The
      results from this study provide interesting implications for health policy,
      health communication strategies and future research.

PMID- 25597492
TI  - Direct growth of GaN layer on carbon nanotube-graphene hybrid structure and its
      application for light emitting diodes.
AB  - We report the growth of high-quality GaN layer on single-walled carbon nanotubes
      (SWCNTs) and graphene hybrid structure (CGH) as intermediate layer between GaN
      and sapphire substrate by metal-organic chemical vapor deposition (MOCVD) and
      fabrication of light emitting diodes (LEDs) using them. The SWCNTs on graphene
      act as nucleation seeds, resulting in the formation of kink bonds along SWCNTs
      with the basal plane of the substrate. In the x-ray diffraction, Raman and
      photoluminescence spectra, high crystalline quality of GaN layer grown on
      CGH/sapphire was observed due to the reduced threading dislocation and efficient
      relaxation of residual compressive strain caused by lateral overgrowth process.
      When applied to the LED structure, the current-voltage characteristics and
      electroluminescence (EL) performance exhibit that blue LEDs fabricated on
      CGH/sapphire well-operate at high injection currents and uniformly emit over the
      whole emission area. We expect that CGH can be applied for the epitaxial growth
      of GaN on various substrates such as Si and MgO, which can be a great advantage
      in electrical and thermal properties of optical devices fabricated on them. 

PMID- 25597494
TI  - Involving relatives in ICU patient care: critical care nursing challenges.
AB  - AIMS AND OBJECTIVES: To identify the barriers critical care nurses experience to
      relative involvement in intensive care unit patient care. BACKGROUND: Previous
      studies have discussed the experiences of relatives visiting an intensive care
      unit, the needs of relatives in the intensive care environment, critical care
      nurse and relative interaction, intensive care unit visiting policies and the
      benefits of including relatives in patient care. The barriers that critical care
      nurses experience to relative involvement in patient care have received minimal
      exploration. DESIGN: Critical care nurses were recruited for a mixed methods
      study. An explanatory mixed method design was used, with two phases. Phase 1 was
      Quantitative and Phase 2 was Qualitative. METHODS: Data collection occurred over
      five months in 2012-2013. Phase 1 used an online questionnaire (n = 70), and semi
      structured interviews (n = 6) were conducted in Phase 2. Phase 1 participants
      were 70 critical care nurses working in Australian intensive care units and six
      critical care nurses were recruited from a single Sydney intensive care unit for
      Phase 2. Through sequential data collection, Phase 1 results formed the
      development of Phase 2 interview questions. RESULTS: Participants reported
      various barriers to relative involvement in critically ill patient care. Factors
      related to the intensive care unit patient, the intensive care unit relative, the
      critical care nurse and the intensive care environment contributed to
      difficulties encompassing relative involvement. CONCLUSIONS: This study has
      identified that when considering relative involvement in patient care, critical
      care nurses take on a paternalistic role. The barriers experienced to relative
      involvement result in the individual critical care nurse deciding to include or
      exclude relatives from patient care. RELEVANCE TO CLINICAL PRACTICE: Knowledge of
      the barriers to relative involvement in critically ill patient care may provide a
      basis for improving discussion on this topic and may assist intensive care units
      to implement strategies to reduce barriers.

PMID- 25597493
TI  - Patient-reported 'ever had' and 'current' long-term physical symptoms after
      prostate cancer treatments.
AB  - OBJECTIVE: To investigate the prevalence of physical symptoms that were 'ever'
      and 'currently' experienced by survivors of prostate cancer at a population
      level, to assess burden and thus inform policy to support survivors. PATIENTS AND
      METHODS: The study included 3 348 men surviving prostate cancer for 2-18 years
      after diagnosis. A cross-sectional, postal survey of 6 559 survivors diagnosed 2
      18 years ago with primary, invasive prostate cancer (ICD10-C61) identified via
      national, population-based cancer registries in Northern Ireland and Republic of
      Ireland. Questions included symptoms at diagnosis, primary treatments and
      physical symptoms (erectile dysfunction [ED]/urinary incontinence [UI]/bowel
      problems/breast changes/loss of libido/hot flashes/fatigue) experienced 'ever'
      and at questionnaire completion ('current'). Symptom proportions were weighted by
      age, country and time since diagnosis. Bonferroni corrections were applied for
      multiple comparisons. RESULTS: Adjusted response rate 54%; 75% reported at least
      one 'current' physical symptom ('ever' 90%), with 29% reporting at least three.
      Prevalence varied by treatment. Overall, 57% reported current ED and this was
      highest after radical prostatectomy (RP, 76%) followed by external beam
      radiotherapy with concurrent hormone therapy (HT, 64%). UI (overall 'current'
      16%) was highest after RP ('current' 28%; 'ever' 70%). While 42% of brachytherapy
      patients reported no 'current' symptoms, 43% reported 'current' ED and 8%
      'current' UI. 'Current' hot flashes (41%), breast changes (18%) and fatigue (28%)
      were reported more often by patients on HT. CONCLUSION: Symptoms after prostate
      cancer treatment are common, often multiple, persist long-term and vary by
      treatment method. They represent a significant health burden. An estimated 1.6%
      of men aged >45 years are survivors of prostate cancer and currently experiencing
      an adverse physical symptom. Recognition and treatment of physical symptoms
      should be prioritised in patient follow-up. This information should facilitate
      men and clinicians when deciding about treatment as differences in survival
      between radical treatments is minimal.

PMID- 25597495
TI  - A Qualitative Exploration of the Use of Attachment Theory in Adult Psychological
      Therapy.
AB  - There is a growing interest into how attachment theory can inform
      psychotherapeutic practice with adults. This study aimed to explore how a group
      of therapists with an interest in attachment theory use it in their work with
      adult clients. A cross-sectional qualitative design was adopted. Sampling, data
      collection and analysis procedures were guided by grounded theory principles.
      Semi-structured telephone interviews were conducted with 12 therapists from a
      variety of training backgrounds. Data were coded and developed into thematic
      categories. Six primary themes were identified to describe how attachment theory
      influenced the clinical practice of the sample through the following: (i)
      complementing other therapeutic models; (ii) providing a framework to understand
      the development of clients' mental health problems; (iii) working with different
      attachment styles; (iv) thinking about the therapeutic relationship as an
      attachment relationship; (iv) influencing the different stages of the therapeutic
      process; and (vi) influencing clinical service design and delivery. It is
      concluded that attachment theory can play a significant role in influencing the
      practice of therapists and can be usefully adopted to complement therapeutic
      processes irrespective of the therapist's dominant clinical orientation. Further
      research is needed to explore the views of clinicians from different theoretical
      orientations and to investigate the security of the client-therapist attachment
      within the context of therapeutic change processes. KEY PRACTITIONER MESSAGE:
      Attachment theory may have implications for practice across a range of different
      types of therapy and may help therapists to bridge apparent differences between
      modality-specific formulation and techniques. Attachment theory can be used to
      understand the development of mental health problems. Therapists should assess
      and formulate clients' attachment styles, and these formulations should guide
      therapeutic approaches. Attachment theory provides a comprehensive framework for
      facilitating the therapist's attentiveness to relational issues and use of the
      therapeutic relationship as a fulcrum for change. The principles of attachment
      theory can be used to inform all stages of the therapeutic process, as well as
      the design and delivery of mental health services.

PMID- 25597497
TI  - Influence of age on resection of colorectal liver metastases.
AB  - BACKGROUND AND OBJECTIVES: Only limited data exist investigating the outcome of
      patients older than 75 years after resection of colorectal liver metastases
      (CLM). Therefore, the present study aims to evaluate clinical and oncological
      outcome of elderly patients. METHODS: A cohort of 405 patients was divided into
      three age-groups: (1) <65 years; (2) 65-75 years; and (3) >75 years of age.
      Patients' data were prospectively collected and retrospectively analyzed. We
      performed survival analysis and added age-correction. Univariate and multivariate
      analysis was performed to determine independent prognostic risk factors. RESULTS:
      The 5-year survival rate of the >75 years age-group was distinctly decreased,
      compared to the other age-groups. After age-correction, the 5-year survival rates
      and the survival curves increased to the greatest extent in patients older than
      75 years. The MSKCC score proved to be a sufficient independent prognostic factor
      in the total patient cohort, patients <65 years and patients 65-75 years. In
      patients older than 75 years, only localization of the primary tumors was a
      significant prognostic factor for overall survival. CONCLUSIONS: Patients' age is
      no reason to deny surgical treatment of CLM. Prognostic factors, such as MSKCC
      score, are not sufficient predictors of survival in patients older than 75 years.

PMID- 25597496
TI  - Artificially engineered Heusler ferrimagnetic superlattice exhibiting
      perpendicular magnetic anisotropy.
AB  - To extend density limits in magnetic recording industry, two separate strategies
      were developed to build the storage bit in last decade, introduction of
      perpendicular magnetic anisotropy (PMA) and adoption of
      ferrimagnetism/antiferromagnetism. Meanwhile, these properties significantly
      improve device performance, such as reducing spin-transfer torque energy
      consumption and decreasing signal-amplitude-loss. However, materials combining
      PMA and antiferromagnetism rather than transition-metal/rare-earth system were
      rarely developed. Here, we develop a new type of ferrimagnetic superlattice
      exhibiting PMA based on abundant Heusler alloy families. The superlattice is
      formed by [MnGa/Co2FeAl] unit with their magnetizations antiparallel aligned. The
      effective anisotropy (K(u)(eff)) over 6 Merg/cm(3) is obtained, and the SL can be
      easily built on various substrates with flexible lattice constants. The coercive
      force, saturation magnetization and K(u)(eff) of SLs are highly controllable by
      varying the thickness of MnGa and Co2FeAl layers. The SLs will supply a new
      choice for magnetic recording and spintronics memory application such as magnetic
      random access memory.

PMID- 25597498
TI  - Human-to-mosquito transmission efficiency increases as malaria is controlled.
AB  - The efficiency of malaria transmission between human and mosquito has been shown
      to be influenced by many factors in the laboratory, although their impact in the
      field and how this changes with disease endemicity are unknown. Here we estimate
      how human-mosquito transmission changed as malaria was controlled in Dielmo,
      Senegal. Mathematical models were fit to data collected between 1990 and the
      start of vector control in 2008. Results show that asexual parasite slide
      prevalence in humans has reduced from 70 to 20%, but that the proportion of
      infectious mosquitoes has remained roughly constant. Evidence suggests that this
      is due to an increase in transmission efficiency caused by a rise in gametocyte
      densities, although the uneven distribution of mosquito bites between hosts could
      also contribute. The resilience of mosquito infection to changes in endemicity
      will have important implications for planning disease control, and the
      development and deployment of transmission-reducing interventions. 

PMID- 25597499
TI  - Genomic medicine and risk prediction across the disease spectrum.
AB  - Genomic medicine is based on the knowledge that virtually every medical
      condition, disease susceptibility or response to treatment is caused, regulated
      or influenced by genes. Genetic testing may therefore add value across the
      disease spectrum, ranging from single-gene disorders with a Mendelian inheritance
      pattern to complex multi-factorial diseases. The critical factors for genomic
      risk prediction are to determine: (1) where the genomic footprint of a particular
      susceptibility or dysfunction resides within this continuum, and (2) to what
      extent the genetic determinants are modified by environmental exposures.
      Regarding the small subset of highly penetrant monogenic disorders, a positive
      family history and early disease onset are mostly sufficient to determine the
      appropriateness of genetic testing in the index case and to inform pre
      symptomatic diagnosis in at-risk family members. In more prevalent polygenic non
      communicable diseases (NCDs), the use of appropriate eligibility criteria is
      required to ensure a balance between benefit and risk. An additional screening
      step may therefore be necessary to identify individuals most likely to benefit
      from genetic testing. This need provided the stimulus for the development of a
      pathology-supported genetic testing (PSGT) service as a new model for the
      translational implementation of genomic medicine in clinical practice. PSGT is
      linked to the establishment of a research database proven to be an invaluable
      resource for the validation of novel and previously described gene-disease
      associations replicated in the South African population for a broad range of NCDs
      associated with increased cardio-metabolic risk. The clinical importance of
      inquiry concerning family history in determining eligibility for personalized
      genotyping was supported beyond its current limited role in diagnosing or
      screening for monogenic subtypes of NCDs. With the recent introduction of
      advanced microarray-based breast cancer subtyping, genetic testing has extended
      beyond the genome of the host to also include tumor gene expression profiling for
      chemotherapy selection. The decreasing cost of next generation sequencing over
      recent years, together with improvement of both laboratory and computational
      protocols, enables the mapping of rare genetic disorders and discovery of shared
      genetic risk factors as novel therapeutic targets across diagnostic boundaries.
      This article reviews the challenges, successes, increasing inter-disciplinary
      integration and evolving strategies for extending PSGT towards exome and whole
      genome sequencing (WGS) within a dynamic framework. Specific points of overlap
      are highlighted between the application of PSGT and exome or WGS, as the next
      logical step in genetically uncharacterized patients for whom a particular
      disease pattern and/or therapeutic failure are not adequately accounted for
      during the PSGT pre-screen. Discrepancies between different next generation
      sequencing platforms and low concordance among variant-calling pipelines caution
      against offering exome or WGS as a stand-alone diagnostic approach. The public
      reference human genome sequence (hg19) contains minor alleles at more than 1
      million loci and variant calling using an advanced major allele reference genome
      sequence is crucial to ensure data integrity. Understanding that genomic risk
      prediction is not deterministic but rather probabilistic provides the opportunity
      for disease prevention and targeted treatment in a way that is unique to each
      individual patient. 

PMID- 25597500
TI  - Lipoprotein lipase and angiopoietin-like 4 - Cardiomyocyte secretory proteins
      that regulate metabolism during diabetic heart disease.
AB  - Cardiac diseases have been extensively studied following diabetes and altered
      metabolism has been implicated in its initiation. In this context, there is a
      shift from glucose utilization to predominantly fatty acid metabolism. We have
      focused on the micro- and macro-environments that the heart uses to provide fatty
      acids to the cardiomyocyte. Specifically, we will discuss the cross talk between
      endothelial cells, smooth muscles and cardiomyocytes, and their respective
      secretory products that allows for this shift in metabolism. These changes will
      then be linked to alterations in the cardiovascular system and the augmented
      heart disease observed during diabetes. Traditionally, the heart was only thought
      of as an organ that supplies oxygen and nutrients to the body through its
      function as a pump. However, the heart as an endocrine organ has also been
      suggested. Secreted products from the cardiomyocytes include the natriuretic
      peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP).
      Both have been shown to have vasodilatory, diuretic and antihypertensive effects.
      These peptides have been extensively studied and their deficiency is considered
      to be a major cause for the initiation of cardiovascular and cardiometabolic
      disorders. Another secretory enzyme, lipoprotein lipase (LPL), has been
      implicated in diabetic heart disease. LPL is a triglyceride-hydrolyzing enzyme
      that is synthesized within the cardiomyocyte and secreted towards the lumen under
      various conditions. For example, moderate or short-term hyperglycemia stimulates
      the release of LPL from the cardiomyocytes towards the endothelial cells. This
      process allows LPL to contact lipoprotein triglycerides, initiating their break
      down, with the product of lipolysis (free fatty acids, FA) translocating towards
      the cardiomyocytes for energy consumption. This mechanism compensates for the
      lack of glucose availability following diabetes. Under prolonged, chronic
      conditions of hyperglycemia, there is a need to inhibit this mechanism to avoid
      the excess delivery of FA to the cardiomyocytes, an effect that is known to
      induce cardiac cell death. Thus, LPL inhibition is made possible by a FA-induced
      activation of PPAR beta/delta, which augments angiopoietin-like 4 (Angptl4), an
      inhibitor of LPL activity. In the current review, we will focus on the mediators
      and conditions that regulate LPL and Angptl4 secretion from the cardiomyocyte,
      which are critical for maintaining cardiac metabolic homeostasis. 

PMID- 25597501
TI  - Novel antiangiogenic drugs for the management of breast cancer: new approaches
      for an old issue?
AB  - Since angiogenesis plays an important role in cancer growth, infiltration and
      metastasis, many agents targeting this pathway have been developed over the last
      decade. Antiangiogenic drugs interfere with this process and may inhibit
      neoplastic growth or induce tumor dormancy by blocking the expanding network of
      newly formed capillaries. Despite the initial promise, targeting angiogenesis in
      breast cancer has not reached major breakthroughs. Nevertheless, the immunologic
      role of VEGF deserves to be further explored. We aim to describe the biological
      mechanisms which underlie the role of angiogenesis in breast cancer
      carcinogenesis, to depict its contribution to the metastatic process and to
      review the most important clinical trials testing angiogenic inhibitors in breast
      cancer, including monoclonal antibodies and novel small molecules. 

PMID- 25597503
TI  - Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both
      ISCU and free thiols.
AB  - Friedreich's ataxia is a severe neurodegenerative disease caused by the decreased
      expression of frataxin, a mitochondrial protein that stimulates iron-sulfur (Fe
      S) cluster biogenesis. In mammals, the primary steps of Fe-S cluster assembly are
      performed by the NFS1-ISD11-ISCU complex via the formation of a persulfide
      intermediate on NFS1. Here we show that frataxin modulates the reactivity of NFS1
      persulfide with thiols. We use maleimide-peptide compounds along with mass
      spectrometry to probe cysteine-persulfide in NFS1 and ISCU. Our data reveal that
      in the presence of ISCU, frataxin enhances the rate of two similar reactions on
      NFS1 persulfide: sulfur transfer to ISCU leading to the accumulation of a
      persulfide on the cysteine C104 of ISCU, and sulfur transfer to small thiols such
      as DTT, L-cysteine and GSH leading to persulfuration of these thiols and
      ultimately sulfide release. These data raise important questions on the
      physiological mechanism of Fe-S cluster assembly and point to a unique function
      of frataxin as an enhancer of sulfur transfer within the NFS1-ISD11-ISCU complex.

PMID- 25597502
TI  - General method for the synthesis of salicylic acids from phenols through
      palladium-catalyzed silanol-directed C-H carboxylation.
AB  - A silanol-directed, palladium-catalyzed C-H carboxylation reaction of phenols to
      give salicylic acids has been developed. This method features high efficiency and
      selectivity, and excellent functional-group tolerance. The generality of this
      method was demonstrated by the carboxylation of estrone and by the synthesis of
      an unsymmetrically o,o'-disubstituted phenolic compound through two sequential C
      H functionalization processes.

PMID- 25597504
TI  - Evaluation of light-emitting diodes (LED) effect on skin biology (in vitro
      study).
AB  - BACKGROUND: Interest in anti-aging approaches has grown significantly in recent
      years. The most popular are the non invasive methods to decrease the signs of
      aging. One such method is LED-based therapy. METHODS: This study investigated the
      potential of two different wavelengths, 590 nm and 630 nm, combined or not, in
      the photobiomodulation of proteins involved in the slowdown of the skin aging.
      RESULTS: These in vitro results on cell viability, cell shape, and mitochondrial
      function support and build on previous studies suggested that LED treatment is
      safe. Regarding its biological functions, our data indicated that the combination
      of two different wavelengths acted in synergy to enhance the impact of each
      irradiation alone. Combined, the LED wavelengths could improve in vitro the cell
      shape, the cell proliferation, and the level of major proteins involved in the
      healing process. CONCLUSION: These benefits may lead to reinforcement of the skin
      organization and structure. This hypothesis will be checked in future clinical
      studies.

PMID- 25597505
TI  - The need to resume chest compressions immediately after defibrillation attempts:
      an analysis of post-shock rhythms and duration of pulselessness following out-of
      hospital cardiac arrest.
AB  - AIM: Current consensus guidelines for cardiopulmonary resuscitation (CPR)
      recommend that chest compressions resume immediately after defibrillation
      attempts and that rhythm and pulse checks be deferred until completion of 5
      compression:ventilation cycles or minimally for 2min. However, data specifically
      confirming the post-shock duration of asystole or pulseless electrical activity
      before return of spontaneous circulation (ROSC) are lacking. Our aim was to
      describe the frequency of the various post-shock cardiac rhythms and the duration
      of post-shock pulselessness in out-of-hospital non-traumatic cardiac arrest.
      METHOD: Using prospectively-collected data from the Resuscitation Outcomes
      Consortium (ROC) Epistry database, the investigators reviewed monitor
      defibrillator recordings of 176 patients who received defibrillation attempts in
      the out-of-hospital setting for ventricular fibrillation (VF) or ventricular
      tachycardia (VT) with absent pulses,. RESULTS: Among 376 different defibrillation
      attempts delivered in the 176 patients, there were 182 resulting episodes of post
      shock asystole. The mean interval of asystole after defibrillation was 69+/-136s
      (median 20s; IQR 36) and the mean interval for return of an organized rhythm was
      64+/-157s (median 7s; IQR 26). The mean time to ROSC was 280+/-320s (median 136s;
      IQR 445). CONCLUSION: After defibrillation attempts, the majority of patients
      remain pulseless for over 2min and the duration of asystole before return of
      pulses is longer than 120s beyond the shock gap in as many as 25%. These data
      support the recommendation to immediately resume chest compressions for 2min
      following attempted defibrillation.

PMID- 25597506
TI  - Mortality and neurological outcome in the elderly after target temperature
      management for out-of-hospital cardiac arrest.
AB  - AIM: To assess older age as a prognostic factor in patients resuscitated from out
      of-hospital-cardiac arrest (OHCA) and the interaction between age and level of
      target temperature management. METHODS AND RESULTS: 950 patients included in the
      target temperature management (TTM) trial were randomly allocated to TTM at 33 or
      36  degrees C for 24h. We assessed survival and cerebral outcome (cerebral
      performance category, CPC and modified Rankin scale, mRS) using age as predictor,
      dividing patients into 5 age groups: <= 65 (median), 66-70, 71-75, 76-80 and >80
      years of age. Shockable rhythm decreased with higher age groups, p = 0.001, the
      same was true for ST segment elevation on ECG at admission, p < 0.01. Increasing
      age was associated with a higher mortality rate (HR = 1.04 per year, 95% CI =
      1.03-1.06, p < 0.001) after adjusting for confounders. Octogenarians had an
      increased mortality (HR = 3.5, CI: 2.5-5.0, p < 0.001) compared to patients <= 65
      years of age. Favorable vs. unfavorable outcome measured by CPC and mRS in
      survivors was different between age groups with adverse outcomes more prevalent
      in higher age groups (CPC: p = 0.04, mRS: p = 0.001). The interaction between age
      and target temperature allocation was not statistically significant for either
      mortality or neurological outcome. CONCLUSION: Increasing age is associated with
      significantly increased mortality after OHCA, but mortality rate is not
      influenced by level of target temperature. Risk of poor neurological outcome also
      increases with age, but is not modified by level of target temperature.

PMID- 25597507
TI  - Individualizing and optimizing the use of early warning scores in acute medical
      care for deteriorating hospitalized patients.
AB  - AIM: While early warning scores (EWS) have the potential to identify
      physiological deterioration in an acute care setting, the implementation of EWS
      in clinical practice has yet to be fully realized. The primary aim of this study
      is to identify optimal patient-centered rapid response team (RRT) activation
      rules using electronic medical records (EMR)-derived Markovian models. METHODS:
      The setting for the observational cohort study included 38,356 adult general
      floor patients hospitalized in 2011. The national early warning score (NEWS) was
      used to measure the patient health condition. Chi-square and Kruskal Wallis tests
      were used to identify statistically significant subpopulations as a function of
      the admission type (medical or surgical), frailty as measured by the Braden skin
      score, and history of prior clinical deterioration (RRT, cardiopulmonary arrest,
      or unscheduled ICU transfer). RESULTS: Statistical tests identified 12
      statistically significant subpopulations which differed clinically, as measured
      by length of stay and time to re-admission (P < .001). The Chi-square test of
      independence results showed a dependency structure between subsequent states in
      the embedded Markov chains (P < .001). The SMDP models identified two sets of
      subpopulation-specific RRT activation rules for each statistically unique
      subpopulation. Clinical deterioration experience in prior hospitalizations did
      not change the RRT activation rules. The thresholds differed as a function of
      admission type and frailty. CONCLUSIONS: EWS were used to identify personalized
      thresholds for RRT activation for statistically significant Markovian patient
      subpopulations as a function of frailty and admission type. The full potential of
      EWS for personalizing acute care delivery is yet to be realized.

PMID- 25597508
TI  - Management of severe acne.
AB  - Acne is the most common skin disease, affecting up to 95% of adolescents. Severe
      episodes of acne can cause considerable physical and psychological scarring, and
      overexpression of transforming growth factor-beta can lead to formation of
      hypertrophic scars and keloids. The severity of acne in adolescence is associated
      with a positive history of severe acne in first-degree relatives, especially the
      mother. In most cases acne is a chronic disease, and it is often a component of
      systemic diseases or syndromes. All forms of severe acne require systemic
      treatment. The available options include oral antibiotics, hormonal antiandrogens
      for female patients and oral isotretinoin, as well as other combination
      treatments. Oral isotretinoin is the only drug available that affects all four
      pathogenic factors of acne. However, due to possible serious side-effects, a
      European directive states that oral isotretinoin should be used only as a second
      line therapy in cases of severe, nodular and conglobate acne. The pharmaceutical
      quality of generic isotretinoin products and the obtainability of isotretinoin
      through e-pharmacies without prescription raise new therapeutic problems. New
      anti-inflammatory compounds, such as the 5-lipoxygenase inhibitor zileuton, may
      replace systemic antibiotics in the future, especially under the scope of
      antibiotic resistance prevention. This review looks into the various options and
      latest approaches, and factors to consider, when combating severe acne. 

PMID- 25597509
TI  - Higher cesarean delivery rates are associated with higher infant mortality rates
      in industrialized countries.
AB  - BACKGROUND: Recent data indicate that more than half of high-income
      industrialized countries have a cesarean delivery rate of  > 25 percent, which is
      higher than the appropriate level considered by most health professionals
      worldwide. METHODS: Data for 31 high-income industrialized countries in 2010 (or
      the nearest year) obtained from the World Health Organization, Organization for
      Economic Cooperation and Development, World Bank, and individual countries were
      analyzed in this study. We examined the correlation between cesarean delivery
      rate and infant mortality rate with Pearson correlation coefficient analysis, and
      examined the independent effect of cesarean delivery on infant mortality with
      multiple linear regression analyses. RESULTS: The cesarean delivery and infant
      mortality rates varied substantially among the included countries: from 15.6 to
      50.0 percent and from 1.9 per to 6.8 per 1,000 live births, respectively.
      Cesarean delivery rates were positively correlated with infant mortality rates
      (Pearson correlation coefficient: 0.41, p < 0.05). The association remained after
      adjustment for maternal age, infant sex, per capita GDP, and the Gini index (p <
      0.03), but disappeared after further adjustment for preterm birth (p = 0.07). In
      a sensitivity analysis, the results were not appreciably affected by excluding
      births at < 22 weeks of gestation, by weighting the data by the number of births
      in each country, or by excluding data from particular countries with possible
      measurement issues (USA, Greece). CONCLUSIONS: A higher cesarean delivery rate is
      associated with higher infant mortality rate among these high-income
      industrialized countries. One of the mechanisms by which cesarean delivery
      affects infant mortality is through iatrogenic prematurity.

PMID- 25597512
TI  - Managing the Cayo Santiago rhesus macaque population: The role of density.
AB  - Cayo Santiago is the oldest continuously operating free-ranging rhesus monkey
      colony in the world. Population control of this colony has historically been
      carried out by periodic live capture and removal of animals. However, the effect
      of such a strategy on the size, growth rate, age structure, and sex ratio of the
      population has not been analyzed. This study reviews past removal data and uses a
      population projection model to simulate the effects of different removal schemes
      based on Cayo Santiago demographic data from 2000-2012. The model incorporates
      negative density-dependence in female fertility, as well as male and female
      survival rates, to determine the population-level effects of selective removal by
      age and sex. Modeling revealed that removal of sexually immature individuals has
      negligible effects on the population dynamics explaining why with an initial
      population of 1309 in 2000 and annual removals of immature monkeys a mean annual
      population growth rate of 12% and a final population size of ~1,435 individuals
      by 2012 (~0.009 animal/m(2) ) was observed. With no removals, the population is
      expected to exhibit dampened oscillations until reaching equilibrium at ~1,690
      individuals (~0.0111 animal/m(2) ) in 2,100. In contrast, removal of adult
      females (>=4 yrs) would significantly reduce the population size, but would also
      promote an increase in population growth rate due to density feedback. A maximum
      annual production of 275 births is expected when 550 adult females are present in
      the population. Sensitivity analyses showed that removing females, in contrast to
      controlling their fertility through invasive treatments would contribute the most
      to changes in population growth rate. Given the density compensation on
      fertility, stabilizing the population would require removing ~80% of the current
      population of adult females. This study highlights the importance of addressing
      the population-level density effects, as well as sensitivity analyses, to
      optimize management strategies.

PMID- 25597511
TI  - CLPB variants associated with autosomal-recessive mitochondrial disorder with
      cataract, neutropenia, epilepsy, and methylglutaconic aciduria.
AB  - 3-methylglutaconic aciduria (3-MGA-uria) is a nonspecific finding associated with
      mitochondrial dysfunction, including defects of oxidative phosphorylation. 3-MGA
      uria is classified into five groups, of which one, type IV, is genetically
      heterogeneous. Here we report five children with a form of type IV 3-MGA-uria
      characterized by cataracts, severe psychomotor regression during febrile
      episodes, epilepsy, neutropenia with frequent infections, and death in early
      childhood. Four of the individuals were of Greenlandic descent, and one was North
      American, of Northern European and Asian descent. Through a combination of
      homozygosity mapping in the Greenlandic individuals and exome sequencing in the
      North American, we identified biallelic variants in the caseinolytic peptidase B
      homolog (CLPB). The causative variants included one missense variant, c.803C>T
      (p.Thr268Met), and two nonsense variants, c.961A>T (p.Lys321*) and c.1249C>T
      (p.Arg417*). The level of CLPB protein was markedly decreased in fibroblasts and
      liver of affected individuals. CLPB is proposed to function as a mitochondrial
      chaperone involved in disaggregation of misfolded proteins, resulting from stress
      such as heat denaturation.

PMID- 25597513
TI  - Age-related changes in physical functioning: correlates between objective and
      self-reported outcomes.
AB  - OBJECTIVES: To quantify the variance attributable to age and estimate annual
      decline in physical function and self-reported health using a battery of outcome
      measures in healthy older females. To determine whether self-reported functional
      losses are similar to those measured objectively and which best represent overall
      physical capacity. DESIGN: Experimental study, cross-sectional analysis. SETTING:
      Human Performance Laboratory, University setting. PARTICIPANTS: Thirty-nine
      community-dwelling women (mean [SD] age=71.5 [7.3] years, range 60 to 83 years)
      completed a battery of objective measures of function and a self-reported health
      status survey. MAIN OUTCOME MEASURES: Objective measures: gait speed; TUG test;
      sit-to-stand; concentric knee flexor and extensor moments; self-reported: the SF
      36. RESULTS: Using a cross-sectional approach, annual declines were estimated
      for: TUG time (2.1%); gait speed (1.2%); knee extensor (2.2%) and flexor moments
      (3.0%); and self-reported Physical Functioning (0.9 to 1.2%) (p<=0.001). Linear
      regression indicated that age explained moderate variance in the objective
      (R(2)=21 to 34%) and self-reported (R(2)=14 to 28%) outcomes. TUG time and gait
      speed was significantly correlated with all objective outcomes except sit-to
      stand (r=0.46 to 0.83) and most of the self-reported (r=0.40 to 0.63) outcomes
      (p<0.01). CONCLUSIONS: Age-related functional deterioration was estimated
      precisely across both objective and self-reported outcomes. Greater strength
      losses for the knee flexors compared to the extensors indicate an unequal
      strength loss of antagonistic muscle pairs which has implications for the safe
      completion of many functional tasks including obstacle negotiation, stair
      locomotion, postural transitions, and ultimately knee joint stability.
      Furthermore, walking speed and TUG time correlated most strongly with many of the
      outcomes highlighting their importance as global indicators of physical capacity.

PMID- 25597510
TI  - CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy,
      intellectual disability, congenital neutropenia, cataracts, movement disorder.
AB  - We studied a group of individuals with elevated urinary excretion of 3
      methylglutaconic acid, neutropenia that can develop into leukemia, a neurological
      phenotype ranging from nonprogressive intellectual disability to a prenatal
      encephalopathy with progressive brain atrophy, movement disorder, cataracts, and
      early death. Exome sequencing of two unrelated individuals and subsequent Sanger
      sequencing of 16 individuals with an overlapping phenotype identified a total of
      14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated
      families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the
      AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of
      this syndrome, we developed a zebrafish model and an in vitro assay to measure
      ATPase activity. Suppression of clpb in zebrafish embryos induced a central
      nervous system phenotype that was consistent with cerebellar and cerebral atrophy
      that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent
      with these data, the loss-of-function effect of one of the identified variants
      (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the
      mutant peptides abolishing ATPase function. Additionally, we show that CLPB
      interacts biochemically with ATP2A2, known to be involved in apoptotic processes
      in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1
      mutations]). Taken together, mutations in CLPB define a syndrome with
      intellectual disability, congenital neutropenia, progressive brain atrophy,
      movement disorder, cataracts, and 3-methylglutaconic aciduria. 

PMID- 25597514
TI  - Biomechanical rationale for implant choices in femoral neck fracture fixation in
      the non-elderly.
AB  - Femoral neck fractures represent a relatively uncommon injury in the non-elderly
      population often resulting from high-energy trauma. The cornerstone of their
      management is anatomic reduction and stable internal fixation of the femoral neck
      in an attempt to salvage the femoral head. Complications including avascular
      necrosis of the femoral head, non-union and post-traumatic osteoarthritis are not
      uncommon. The clinical outcomes of these patients can be improved with good pre
      operative planning, optimization of surgical procedures and introduction of new
      improved implants and techniques. In the herein study, we attempt to describe the
      biomechanical properties of the hip and compare the performance of the most
      commonly used devices. Experimental evidence suggests that in Pauwels type III
      fracture patterns a cephalomedullary nail was significantly stronger in axial
      loading. Moreover, in unstable basicervical patterns cannulated screws
      (triangular configuration) demonstrated a lower ultimate load to failure, whereas
      in subcapital or transervical patterns both the cannulated screws (triangular
      configuration) and the sliding hip screw demonstrated no compromise in fixation
      strength. The fracture pattern appears to be the major determinant of the ideal
      type of implant to be selected. For a successful outcome each patient needs to be
      considered on an individual basis taking into account all patient and implant
      related factors. 

PMID- 25597515
TI  - Effects of Rosmarinus officinalis L. essential oils supplementation on digestion,
      colostrum production of dairy ewes and lamb mortality and growth.
AB  - The aim of this study was to evaluate the effect of rosemary essential oils (REO)
      and the forage nature on ewes' performances, immune response and lambs' growth
      and mortality. Forty-eight dairy ewes (Sicilo-Sarde) were fed oat-hay or oat
      silage supplemented with 400 g of concentrate during pregnancy and 600 g during
      postpartum. The experimental concentrate contained the same mixture as the
      control (barley, soybean meal and mineral vitamin supplement) more 0.6 g/kg of
      REO. Two groups were obtained with each forage (Hay groups: H-C and H-REO; Silage
      groups: S-C and S-REO). REO increased the dry matter (DM) intake, the nitrogen
      intake and retention being higher with the silage groups (P < 0.05). REO
      increased solid non-fat (P = 0.004) and fat contents of colostrum which was
      higher with hay (P = 0.002). REO decreased lamb mortality (P < 0.05) which
      averaged 21% for control groups and 6% for H-REO, while no mortality was recorded
      with S-REO. REO dietary supply improved forage intake and tended to ameliorate
      colostrum production; it could be a natural additive to improve ewes'
      performances.

PMID- 25597516
TI  - Isolation and identification of phenolic antioxidants in black rice bran.
AB  - Black rice bran contains phenolic compounds of a high antioxidant activity. In
      this study, the 40% acetone extract of black rice bran was sequentially
      fractionated to obtain 5 fractions. Out of the 5 fractions, ethyl acetate
      fraction was subfractionated using the Sephadex LH-20 chromatography. The
      antioxidant activity of phenolic compounds in the extracts was investigated by
      2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, 2,2-azino-bis-(3
      ethylenebenzothiozoline-6-sulfonic acid) (ABTS) radical cation assay, reducing
      power. The subfraction 2 from ethyl acetate fraction had the highest total
      phenolic contents (TPC) (816.0 MUg/mg) and the lowest EC50 values (47.8 MUg/mL
      for DPPH radical assay, 112.8 MUg/mL for ABTS radical cation assay, and 49.2
      MUg/mL for reducing power). These results were 3.1, 1.3, and 2.6 times lower than
      those of butylated hydroxytoluene (BHT), respectively. At a concentration of 100
      MUg/mL, the antioxidant activity and TPC of various extracts was closely
      correlated, with correlation coefficients (R(2) ) higher than 0.86. The major
      phenolic acid in subfraction 2 was identified as ferulic acid (178.3 MUg/mg) by
      HPLC and LC-ESI/MS/MS analyses. Our finding identified ferulic acid as a major
      phenolic compound in black rice bran, and supports the potential use of black
      rice bran as a natural source of antioxidant. 

PMID- 25597517
TI  - A soft/hard magnetic nanostructure based on multisegmented CoNi nanowires.
AB  - In this paper we have introduced a new soft/hard nanostructure based on
      multisegmented CoNi nanowire arrays having diameters of around 110 nm and made of
      five segments with nominal compositions of Co, Co66Ni33, Co50Ni50, Co33Ni66 and
      Ni, each of which has a length of 800 nm, so that the total length of the
      multisegmented nanowire is 4 MUm. These arrays have been synthesized by means of
      potentiostatic electrodeposition into the pores of hard-anodic alumina templates.
      The morphology, chemical composition and microstructure of the multisegmented
      CoNi nanowires were determined by high-resolution scanning electron microscopy,
      energy dispersive X-ray microanalysis, and powder X-ray diffraction method,
      respectively. The room temperature magnetic behavior of the multisegmented
      nanowire arrays is also studied and compared with CoNi nanowire arrays with
      homogeneous composition (non-segmented nanowires), synthesized in the same
      templates and having the same dimensions as the segmented ones. These
      nanostructures could be used to control the movement of magnetic domain walls. In
      this way, these nanostructures can be an alternative to store information or even
      perform logic functions. 

PMID- 25597518
TI  - Stereo-particle image velocimetry measurements of a patient-specific Fontan
      physiology utilizing novel pressure augmentation stents.
AB  - Single ventricle anomalies are a challenging set of congenital heart defects that
      require lifelong clinical management due to progressive decline of cardiovascular
      function. Few therapeutic devices are available for these patients, and
      conventional blood pumps are not designed for the unique anatomy of the single
      ventricle physiology. To address this unmet need, we are developing an axial flow
      blood pump with a protective cage or stent for Fontan patients. This study
      investigates the 3-D particle image velocimetry measurements of two cage designs
      being deployed in a patient-specific Fontan anatomy. We considered a control case
      without a pump, impeller placed in the inferior vena cava, and two cases where
      the impeller has two protective stents with unique geometric characteristics. The
      experiments were evaluated at a cardiac output of 3 L/min, a fixed vena caval
      flow split of 40%/60%, a fixed pulmonary arterial flow split of 50%/50%, and for
      operating speeds of 1000-4000 rpm. The introduction of the cardiovascular stents
      had a substantial impact on the flow conditions leaving the pump and entering the
      cavopulmonary circulation. The findings indicated that rotational speeds above
      4000 rpm for this pump could result in irregular flows in this specific
      circulatory condition. Although retrograde flow into the superior vena cava was
      not measured, the risk of this occurrence increases with higher pump speeds. The
      against-with stent geometry outperformed the other configurations by generating
      higher pressures and more energetic flows. These results provide further support
      for the viability of mechanical cavopulmonary assistance as a therapeutic
      treatment strategy for Fontan patients. 

PMID- 25597519
TI  - Transfer of antibiotic-resistance genes via phage-related mobile elements.
AB  - Antibiotic resistance is a major concern for society because it threatens the
      effective prevention of infectious diseases. While some bacterial strains display
      intrinsic resistance, others achieve antibiotic resistance by mutation, by the
      recombination of foreign DNA into the chromosome or by horizontal gene
      acquisition. In many cases, these three mechanisms operate together. Several
      mobile genetic elements (MGEs) have been reported to mobilize different types of
      resistance genes and despite sharing common features, they are often considered
      and studied separately. Bacteriophages and phage-related particles have recently
      been highlighted as MGEs that transfer antibiotic resistance. This review focuses
      on phages, phage-related elements and on composite MGEs (phages-MGEs) involved in
      antibiotic resistance mobility. We review common features of these elements,
      rather than differences, and provide a broad overview of the antibiotic
      resistance transfer mechanisms observed in nature, which is a necessary first
      step to controlling them. 

PMID- 25597520
TI  - Calcium entry via connexin hemichannels in lens epithelium.
AB  - Exposure to hyposmotic solution causes release of ATP from lens cells via
      hemichannels. Because hemichannel opening feasibly could swamp the cells with
      calcium, we carried out studies to measure the magnitude of the increase in
      cytoplasmic calcium concentration caused by hemichannel opening. In studies on
      porcine lens epithelial cells in primary culture, propidium iodide (PI) uptake
      was measured as an index of hemichannel opening. PI uptake was increased
      significantly in cells exposed to hyposmotic solution. The PI increase under
      hyposmotic conditions was suppressed by GAP 27, a connexin inhibitor peptide. In
      studies on cells loaded with Fura-2, continuous exposure to hyposmotic solution
      caused a cytoplasmic calcium concentration increase that peaked within ~30 s then
      remained elevated at or below the peak response for more than 60 min. The peak
      calcium concentration was 186 +/- 2.3 nM compared to a baseline value of 98.0 +/-
      1.4 nM. The calcium concentration increased a lot further in cells exposed to
      A23187 (2.5 MUM) or the sodium-calcium exchange inhibitor SN-6 (10 MUM) added
      after the onset of the calcium rise in hyposmotic solution. The cytoplasmic
      calcium increase in hyposmotic solution was abolished by GAP 27. Calcium returned
      to baseline in cells exposed to hyposmotic solution then treated with GAP 27
      starting 2 min after the onset of the calcium rise. The calcium increase in
      hyposmotic solution did not occur when calcium was eliminated from the bathing
      medium. The responses to hyposmotic and hyperosmotic stress were different. There
      was no detectable increase in calcium or PI entry in cells exposed to
      hyperosmotic solution (500mOsm). In summary, GAP 27-sensitive accumulation of PI
      by cultured lens epithelium points to connexin hemichannel opening and associated
      calcium entry. Even though connexins form channels with a large carrying
      capacity, calcium entry does not increase the cytoplasmic calcium concentration
      beyond a tolerable physiological range. 

PMID- 25597521
TI  - How the flexibility of human histone deacetylases influences ligand binding: an
      overview.
AB  - Over the past decade, human histone deacetylases (HDACs) have become interesting
      as therapeutic targets because of the benefits that their modulation might
      provide in aging-related disorders. Recently, studies using crystallography and
      computational chemistry have provided information on the structure and
      conformational changes related to HDAC-mediated recognition events. Through the
      description of the key mass and one-off movements observed in metal-dependent
      HDACs, here we highlight the impact of flexibility on drug-binding affinity and
      specificity. The collected information will be useful for not only a better
      understanding of the biological functions of HDACs, but also the conception of
      new selective binders. 

PMID- 25597522
TI  - Frontier nurse-midwives and antepartum emergencies, 1925 to 1939.
AB  - This article examines how the Frontier Nursing Service (FNS) utilized nurse
      midwives to respond to antepartum emergencies such as preterm birth, eclampsia,
      malpresentation, and hemorrhage in the women of Appalachia in the years 1925 to
      1939. Particular attention is given to the preparation that nurse-midwives
      received during their midwifery education to prevent and respond to emergencies.
      Using traditional historical research methods and primary source material from
      the FNS papers in the Special Collections, University of Kentucky Libraries,
      Lexington, Kentucky, this article describes the nurse-midwives' experiences and
      how they implemented skills they had learned during their training in Great
      Britain. Working in the isolated mountainous area of Leslie County, Kentucky-for
      the most part without direct assistance from physicians-FNS nurse-midwives
      decreased maternal and neonatal mortality rates. During their first 2000 births,
      they had only 2 maternal deaths, whereas the national average maternal mortality
      rate was approximately 7 deaths per 1000 births. The nurse-midwives performed
      external cephalic versions on a routine basis. For pregnancy and birth
      emergencies, they administered sedation, gave general anesthesia, and performed
      invasive lifesaving techniques in order to protect the lives of the women in
      their care. During these 14 years, their cross-cultural engagement, assessment
      skills, clinical judgment, and timely interventions improved maternal and child
      health throughout the region. 

PMID- 25597523
TI  - Epstein-Barr virus-positive diffuse large B-cell primary central nervous system
      lymphoma associated with organized chronic subdural hematoma: a case report and
      review of the literature.
AB  - We here report on a rare case of Epstein-Barr virus (EBV)-positive diffuse large
      B-cell lymphoma (DLBCL) detected in both brain parenchyma and in an organized
      chronic subdural hematoma (OCSH). A 96-year-old man diagnosed with asymptomatic
      OCSH in the left frontal convexity was referred to our hospital because of a de
      novo mass lesion just beneath the OCSH on contrast-enhanced magnetic resonance
      imaging. The size of the OCSH remained stable. We diagnosed the lesion as a
      malignant tumor. At surgery, the organized hematoma and the soft fragile tumor
      were removed. Histological examinations revealed pleomorphic lymphoid cells not
      only in the brain tissue but also in the OCSH component with tumor necrosis, and
      these were immunopositive for B-cell markers. In situ hybridization revealed
      positive signals for EBV-encoded small RNAs, consistent with EBV-positive DLBCL.
      Since the membranes of the subdural hematoma were fibrous and the tumor
      progression resulted in necrosis of the tumor, the DLBCL may have originally
      developed in the OCSH and infiltrated into the brain parenchyma. We believe that
      this rare case provides crucial information for the understanding of DLBCLs
      associated with OCSH. 

PMID- 25597524
TI  - Dissociable spatial and non-spatial attentional deficits after circumscribed
      thalamic stroke.
AB  - Thalamic nuclei act as sensory, motor and cognitive relays between multiple
      subcortical areas and the cerebral cortex. They play a crucial role in cognitive
      functions such as executive functioning, memory and attention. In the acute
      period after thalamic stroke attentional deficits are common. The precise
      functional relevance of specific nuclei or vascular sub regions of the thalamus
      for attentional sub functions is still unclear. The theory of visual attention
      (TVA) allows the measurement of four independent attentional parameters (visual
      short term memory storage capacity (VSTM), visual perceptual processing speed,
      selective control and spatial weighting). We combined parameter-based assessment
      based on TVA with lesion symptom mapping in standard stereotactic space in
      sixteen patients (mean age 41.2 +/- 11.0 SD, 6 females), with focal thalamic
      lesions in the medial (N = 9), lateral (N = 5), anterior (N = 1) or posterior (N
      = 1) vascular territories of the thalamus. Compared with an age-matched control
      group of 52 subjects (mean age 40.1 +/- 6.4, 35 females), the patients with
      thalamic lesions were, on the group level, mildly impaired in visual processing
      speed and VSTM. Patients with lateral thalamic lesions showed a deficit in
      processing speed while all other TVA parameters were within the normal range.
      Medial thalamic lesions can be associated with a spatial bias and extinction of
      targets either in the ipsilesional or the contralesional field. A posterior case
      with a thalamic lesion of the pulvinar replicated a finding of Habekost and
      Rostrup (2006), demonstrating a spatial bias to the ipsilesional field, as
      suggested by the neural theory of visual attention (NTVA) (Bundesen, Habekost, &
      Kyllingsbaek, 2011). A case with an anterior-medial thalamic lesion showed
      reduced selective attentional control. We conclude that lesions in distinct
      vascular sub regions of the thalamus are associated with distinct attentional
      syndromes (medial = spatial bias, lateral = processing speed).

PMID- 25597525
TI  - Changes in pattern completion--a key mechanism to explain age-related recognition
      memory deficits?
AB  - Accurate memory retrieval from partial or degraded input requires the
      reactivation of memory traces, a hippocampal mechanism termed pattern completion.
      Age-related changes in hippocampal integrity have been hypothesized to shift the
      balance of memory processes in favor of the retrieval of already stored
      information (pattern completion), to the detriment of encoding new events
      (pattern separation). Using a novel behavioral paradigm, we investigated the
      impact of cognitive aging (1) on recognition performance across different levels
      of stimulus completeness, and (2) on potential response biases. Participants were
      required to identify previously learned scenes among new ones. Additionally, all
      stimuli were presented in gradually masked versions to alter stimulus
      completeness. Both young and older adults performed increasingly poorly as the
      scenes became less complete, and this decline in performance was more pronounced
      in elderly participants indicative of a pattern completion deficit. Intriguingly,
      when novel scenes were shown, only the older adults showed an increased tendency
      to identify these as familiar scenes. In line with theoretical models, we argue
      that this reflects an age-related bias towards pattern completion. 

PMID- 25597526
TI  - Depression screening in pediatric epilepsy: evidence for the benefit of a
      behavioral medicine service in early detection.
AB  - Despite the increased risk and prevalence of depression in youth with epilepsy,
      only one-third receive mental health services. Untreated depression can
      contribute to negative outcomes and increased health-care utilization and medical
      cost. Proactive behavioral medicine screening may facilitate identification of
      depressive symptoms and necessary interventions in efforts to optimize behavioral
      health and health-related quality of life (HRQOL). Primary study aims included
      the examination of 1) rates of self-reported depression in youth with epilepsy,
      2) differences in depression by demographic and medical variables, 3) the impact
      of depression on HRQOL, and 4) changes in depression and suicidal ideation
      following a behavioral medicine consultation. As part of routine clinic care over
      a 24-month period, youth with epilepsy of 7-17years of age completed the
      Children's Depression Inventory-Second Edition. Parents completed the PedsQL. A
      chart review was conducted to ascertain demographics, medical variables, and
      behavioral medicine visits and recommendations. A subsample with Time 1 and Time
      2 depression data was examined. Time 1 participants included 311 youth with
      epilepsy (Mage=11.9years, 50% female, 84% Caucasian, 46.0% with localization
      related epilepsy, 71.0% with seizure control in the past 3months). Elevated
      depression was identified in 23% of youth, with 14% endorsing suicidal ideation.
      Depression significantly varied by age, antiepileptic drug, and insurance. After
      controlling for seizure status, HRQOL worsened with elevated depression.
      Depression significantly decreased from Time 1 to Time 2 (n=159), particularly
      for those referred for behavioral medicine services at Time 1. Systematic
      assessment and early detection of depression and/or suicidal ideation in youth
      with epilepsy can improve HRQOL and decrease depression. Depression screening can
      be implemented through clinic-based behavioral medicine services. 

PMID- 25597527
TI  - One step closer to a global tool for rapid screening of major depression in
      epilepsy: validation of the French NDDI-E.
AB  - OBJECTIVE: Depression in people with epilepsy (PWE) is underdiagnosed and
      undertreated. The Neurological Disorders Depression Inventory for Epilepsy (NDDI
      E) is a screening questionnaire used for detecting major depressive episode (MDE)
      in PWE, and is already validated in 10 languages. However a version in French,
      one of the world's widely spoken languages, was, until now, lacking. We aimed to
      translate and validate the French NDDI-E. METHODS: This study was performed under
      the auspices of the ILAE. People with epilepsy >18years of age were recruited
      from 2 specialist epilepsy units in Marseille, France. Two native French speakers
      and 2 native English speakers performed a forward-backward translation. The Mini
      International Neuropsychiatric Interview (MINI) was performed as the gold
      standard, and the Center for Epidemiological Studies Depression symptoms index
      (CES-D) was performed for external validity. Data were compared between PWE with
      MDE and PWE without MDE using the chi-square test and Student's t-test. Internal
      structural validity, external validity, and receiver operator characteristics
      were analyzed. RESULTS: Testing was performed on 116 PWE: mean age=40.39years
      (SD=13.83, range: [18-81]years old); 58.6% (68) were women; 87.1% had focal
      epilepsy. Using the MINI, we found that 33 (28.4%) patients had current MDE and
      that 15 (12.9%) patients had dysthymia; also, we found that 37 (31.9%) patients
      presented suicidal ideation and/or behavior. Cronbach's alpha coefficient was
      0.838, indicating satisfactory internal consistency. Correlation between the NDDI
      E and the CES-D scores was high (r(116)=0.817, p<0.0001), indicating good
      external validity. Receiver operator characteristic analysis showed an area under
      the curve of 0.958 (95% CI=0.904-0.986), (p<0.0001), indicating good capacity of
      the NDDI-E to detect MDE (defined by MINI). The cutoff for maximal sensitivity
      and specificity was 15. The mean NDDI-E score in PWE with MDE was 18.27
      (SD=2.28), and the mean NDDI-E score in PWE without MDE was 10.61 (SD=3.63).
      SIGNIFICANCE: This study validated the French NDDI-E, with a cutoff score of
      15/24 for MDE, similar to previous studies, and reinforces the NDDI-E as a global
      tool for detection of MDE.

PMID- 25597528
TI  - Neuropsychological functioning in children with temporal lobe epilepsy and
      hippocampal atrophy without mesial temporal sclerosis: a distinct clinical
      entity?
AB  - Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial
      temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. However,
      in other cases, it has been suggested that HA without MTS may constitute a
      distinct epileptic entity. Hippocampal atrophy without MTS was defined as HA
      without T2-weighted hyperintensity, loss of internal architecture, or associated
      lesion seen on the MRI data. To date, no study has focused on the cognitive
      pattern of children with epilepsy with HA without MTS. The objectives of the
      present study were to characterize the cognitive profile of these children and to
      investigate the presence (or the absence) of material-specific memory deficits in
      these young patients, as found in patients with MTS. Toward this end, 16 young
      patients with epilepsy with either left or right HA without MTS completed a set
      of neuropsychological tests, assessing overall intelligence, verbal memory and
      nonverbal memory, and some aspects of attention and executive functions. Results
      showed normal intellectual functioning without specific memory deficits in these
      patients. Furthermore, comparison between patients with left HA and patients with
      right HA failed to reveal a material-specific lateralized memory pattern.
      Instead, attention and executive functions were found to be impaired in most
      patients. These results suggest that HA may constitute a distinct epileptic
      entity, and this information may help health-care providers initiate appropriate
      and timely interventions. 

PMID- 25597529
TI  - Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major
      depressive disorder: a phase II, sham-controlled, randomized clinical trial.
AB  - BACKGROUND: Considering both the burden determined by major depressive disorder
      (MDD) itself and the high refractoriness and recurrence index, alternative
      strategies, such as trigeminal nerve stimulation (TNS), are the cutting edge
      instruments to optimize clinical response and to avoid treatment discontinuation
      and relapse of symptoms. Trigeminal nerve stimulation is an incipient simple, low
      cost interventional strategy based on the application of an electric current over
      a branch of the trigeminal nerve with further propagation of the stimuli towards
      brain areas related to mood symptoms. METHOD: The study was a phase II,
      randomized, sham-controlled trial with 40 patients with MDD. Patients with
      moderate or severe depressive symptoms as assessed by adequate clinical scales
      underwent a 10-day intervention protocol. Regarding main clinical outcome,
      analysis of variance (ANOVA) was performed to evaluate mean change scores in
      depressive symptoms as assessed by the HDRS-17 between baseline (t1), after
      intervention protocol (t2), and during one-month follow-up (t3). RESULTS: There
      was a significant interaction between the mean percentage changes in depressive
      symptoms according to the HDRS in the two groups across the three assessments
      (F=6.38, df=2, p=0.0033). Post hoc analyses (Bonferroni method) demonstrated a
      statistically significant difference between depressive symptoms at baseline and
      t1 (p=0.01) and between depressive symptoms at baseline and t2 (p=0.009). No
      severe adverse effects were reported. DISCUSSION: Our results in the present
      controlled trial highlight the possibility of more practical treatment protocols
      for clinical research, which are similar to those for different neuromodulation
      strategies such as transcranial direct current stimulation (tDCS). The in-office
      administration of TNS in our protocol is similar to the schedule for repetitive
      transcranial magnetic stimulation (rTMS), though over fewer treatment sessions.
      CONCLUSION: Further controlled studies will contribute to the establishment of
      the clinical relevance of this new treatment strategy for MDD.

PMID- 25597531
TI  - Polymeric micelles in mucosal drug delivery: Challenges towards clinical
      translation.
AB  - Polymeric micelles are nanostructures formed by the self-aggregation of
      copolymeric amphiphiles above the critical micellar concentration. Due to the
      flexibility to tailor different molecular features, they have been exploited to
      encapsulate motley poorly-water soluble therapeutic agents. Moreover, the
      possibility to combine different amphiphiles in one single aggregate and produce
      mixed micelles that capitalize on the features of the different components
      substantially expands the therapeutic potential of these nanocarriers. Despite
      their proven versatility, polymeric micelles remain elusive to the market and
      only a few products are currently undergoing advanced clinical trials or reached
      clinical application, all of them for the therapy of different types of cancer
      and administration by the intravenous route. At the same time, they emerge as a
      nanotechnology platform with great potential for non-parenteral mucosal
      administration. However, for this, the interaction of polymeric micelles with
      mucus needs to be strengthened. The present review describes the different
      attempts to develop mucoadhesive polymeric micelles and discusses the challenges
      faced in the near future for a successful bench-to-bedside translation. 

PMID- 25597530
TI  - A readily available colorimetric and near-infrared fluorescent turn-on probe for
      rapid and selective detection of cysteine in living cells.
AB  - A readily available naphthofluorescein-based near-infrared (NIR) fluorescent
      probe was reported for rapid, colorimetric and NIR fluorescent turn-on detection
      of cysteine (Cys) with high selectivity and sensitivity over various analytes
      including the similar structured homocysteine (Hcy) and glutathione (GSH). This
      probe was successfully applied to bioimage intracellular Cys in living cells with
      low cytotoxicity. 

PMID- 25597532
TI  - Polarized single photon emission and photon bunching from an InGaN quantum dot on
      a GaN micropyramid.
AB  - We report on excitonic single photon emission and biexcitonic photon bunching
      from an InGaN quantum dot formed on the apex of a hexagonal GaN micropyramid. An
      approach to suppress uncorrelated emission from the pyramid base is proposed, a
      metal film is demonstrated to effectively screen background emission and thereby
      significantly enhance the signal-to-background ratio of the quantum dot emission.
      As a result, the second order coherence function at zero time delay g(2)(0) is
      significantly reduced (to g(2)(0) = 0.24, raw value) for the excitonic
      autocorrelation at a temperature of 12 K under continuous wave excitation, and a
      dominating single photon emission is demonstrated to survive up to 50 K. The
      deterioration of the g(2)(0)-value at elevated temperatures is well understood as
      the combined effect of reduced signal-to-background ratio and limited time
      resolution of the setup. This result underlines the great potential of site
      controlled pyramidal dots as sources of fast polarized single photons.

PMID- 25597533
TI  - Valence holes observed in nanodiamonds dispersed in water.
AB  - Colloidal dispersion is essential for most nanodiamond applications, but its
      influence on nanodiamond electronic properties remains unknown. Here we have
      probed the electronic structure of oxidized detonation nanodiamonds dispersed in
      water by using soft X-ray absorption and emission spectroscopies at the carbon
      and oxygen K edges. Upon dispersion in water, the pi* transitions from sp(2)
      hybridized carbon disappear, and holes in the valence band are observed. 

PMID- 25597534
TI  - Fluorescence imaging of selenol in HepG2 cell apoptosis induced by Na2SeO3.
AB  - A novel fluorescence probe (HB) has been designed and synthesized to image
      selenol in living cells and in vivo for the first time, and used to investigate
      the Na2SeO3 anticancer mechanism in HepG2 cells. 

PMID- 25597535
TI  - Ion Move Brownian Dynamics (IMBD)--simulations of ion transport.
AB  - PURPOSE: Comparison of the computed characteristics and physiological measurement
      of ion transport through transmembrane proteins could be a useful method to
      assess the quality of protein structures. Simulations of ion transport should be
      detailed but also timeefficient. METHODS: The most accurate method could be
      Molecular Dynamics (MD), which is very time-consuming, hence is not used for this
      purpose. The model which includes ion-ion interactions and reduces the simulation
      time by excluding water, protein and lipid molecules is Brownian Dynamics (BD).
      In this paper a new computer program for BD simulation of the ion transport is
      presented. We evaluate two methods for calculating the pore accessibility (round
      and irregular shape) and two representations of ion sizes (van der Waals diameter
      and one voxel). RESULTS: Ion Move Brownian Dynamics (IMBD) was tested with two
      nanopores: alpha-hemolysin and potassium channel KcsA. In both cases during the
      simulation an ion passed through the pore in less than 32 ns. Although two types
      of ions were in solution (potassium and chloride), only ions which agreed with
      the selectivity properties of the channels passed through the pores. CONCLUSIONS:
      IMBD is a new tool for the ion transport modelling, which can be used in the
      simulations of wide and narrow pores.

PMID- 25597536
TI  - Magnetofluorescent micellar complexes of terbium(III) as potential bimodal
      contrast agents for magnetic resonance and optical imaging.
AB  - Terbium(III) was coordinated to four novel 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTA) amphiphilic bisamide ligands. The complexes were
      assembled into mono-disperse micellar nano-aggregates and for the first time
      Tb(III) has been evaluated as a single lanthanide negative bimodal contrast agent
      for MRI/OI. The complexes show characteristic Tb(III) emission with quantum
      yields reaching 7.3% and transverse relaxivity r2 per Tb(III) micelle at 500 MHz
      and 310 K reaches maximum values up to 60 s(-1) micelle(-1). The efficient T2
      relaxation at high magnetic field strengths is sustained by the increased
      rotational correlation time of the nano-aggregates and high magnetic moment of
      the terbium ion.

PMID- 25597537
TI  - Synthesis and characterization of substituted Schiff-base ligands and their d(10)
      metal complexes: structure-induced luminescence tuning behaviors and applications
      in co-sensitized solar cells.
AB  - Nine IIB group complexes, [ZnL1Cl2] (Zn1), [CdL1Cl2]2 (Cd1), [HgL1Cl2] (Hg1),
      [ZnL2Cl2] (Zn2), [CdL2Cl2] (Cd2), [HgL2Cl2] (Hg2), [ZnL3Cl2] (Zn3), [CdL3Cl2]
      (Cd3) and [HgL3Cl2] (Hg3), have been synthesized from the corresponding ortho-(6
      methoxy-pyridyl)(CH[double bond, length as m-dash]NAr) (where Ar = 2,6-iPr2C6H3,
      L1; 4-MeC6H4, L2; 2-OMeC6H4, L3) Schiff base and structurally characterized by
      elemental analysis, FT-IR, (1)H NMR and X-ray single-crystal analysis.
      Crystallographic studies reveal that the center metal of the complexes adopts a
      distorted tetrahedron geometry (except for Cd1 and Cd3, which display square
      pyramidal geometry) and C-HCl hydrogen bonds and pipi stacking interactions
      contribute to three-dimensional supramolecular structures. The series of
      complexes exhibit tunable luminescence from blue, through green, to light yellow
      by varying the temperature (298 K and 77 K), both in solution and in the solid
      state. Moreover, the quantum yields range from 0.027 to 0.422, and decrease
      according to the order of the periodic table (Zn > Cd > Hg). These results
      indicate that the center atom of the complexes leads to the geometry differences
      and hence to the tunable luminescence properties. Because Zn1-Zn3 exhibited
      higher molar extinction coefficients and a distinct absorption region, they were
      employed as co-sensitizers in ruthenium dye N719-sensitized photoanodes to
      deliver light-electricity efficiency enhancement, being assembled with counter
      electrodes and electrolyte to prepare ZnX/N719 (where ZnX = Zn1, Zn2, and Zn3) co
      sensitized dye sensitized solar cell (DSSC) devices. The prepared co-absorbent
      could overcome the deficiency of N719 absorption in the low-wavelength region of
      the visible spectrum, and offset competitive visible-light absorption of I3(-).
      Application of these prepared complexes in N719-sensitized solar cells enhanced
      their performance by 10-36%, which indicated a potential application of these
      types of complexes in DSSCs.

PMID- 25597538
TI  - Comparing introduction to Europe of highly pathogenic avian influenza viruses
      A(H5N8) in 2014 and A(H5N1) in 2005.
AB  - Since the beginning of November 2014, nine outbreaks of highly pathogenic avian
      influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European
      countries. In this report, similarities and differences between the modes of
      introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences
      from outbreaks of A(H5N1) in Europe demonstrated that early detection to control
      HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission
      and prevention of human cases.

PMID- 25597539
TI  - ESwab challenges influenza virus propagation in cell cultures.
AB  - Although the ESwab kit (Copan, Brescia, Italy) is intended for sampling bacteria
      for culture, this kit is increasingly also used for virus sampling. The effect of
      ESwab medium on influenza virus detection by real-time reverse transcription
      polymerase chain reaction (RT-PCR) or virus propagation in Madin-Darby canine
      kidney (MDCK) cell culture was investigated. The ESwab medium was suitable for
      viral RNA detection but not for viral propagation due to cytotoxicity. Sampling
      influenza viruses with ESwab challenges influenza surveillance by strongly
      limiting the possibility of antigenic characterisation.

PMID- 25597540
TI  - A large community outbreak of Legionnaires disease in Vila Franca de Xira,
      Portugal, October to November 2014.
AB  - An outbreak of Legionnaires' disease with 334 confirmed cases was identified on 7
      November 2014 in Vila Franca de Xira, Portugal and declared controlled by 21
      November. Epidemiological, environmental and microbiological analysis identified
      industrial wet cooling systems to be the probable source of infection.
      Preliminary results from sequence-based typing of clinical specimens and
      environmental isolates confirmed this link. A series of meteorological phenomena
      are likely to have contributed to the scale of this outbreak.

PMID- 25597541
TI  - Foodborne hepatitis A outbreak associated with bakery products in northern
      Germany, 2012.
AB  - In October 2012, a hepatitis A (HA) outbreak with 83 laboratory-confirmed cases
      occurred in Lower Saxony. We defined primary outbreak cases as people with
      laboratory-confirmed HA and symptom onset between 8 October and 12 November 2012,
      residing in or visiting the affected districts. Secondary outbreak cases were
      persons with symptom onset after 12 November 2012 and close contact with primary
      cases. We identified 77 primary and six secondary cases. We enrolled 50 primary
      cases and 52 controls matched for age and sex, and found that 82% of cases and
      60% of controls had consumed products from a particular bakery (OR=3.09; 95% CI:
      1.15-8.68). Cases were more likely to have eaten sweet pastries (OR=5.74; 95% CI:
      1.46-22.42). Viral isolates from five selected cases and three positively tested
      surfaces in the bakery had identical nucleotide sequences. One additional
      identical isolate derived from a salesperson of the bakery suffering from a
      chronic disease that required immunosuppressive treatment. Epidemiological and
      laboratory findings suggested that the salesperson contaminated products while
      packing and selling. Future risk assessment should determine whether food
      handlers with chronic diseases under immunosuppressive treatment could be more at
      risk of contaminating food and might benefit from HAV immunisation.

PMID- 25597542
TI  - Innovative applications of immunisation registration information systems: example
      of improved measles control in Taiwan.
AB  - Immunisation registry systems have been shown to be important for finding pockets
      of under-immunised individuals and for increasing vaccination coverage. The
      National Immunisation Information System (NIIS) was established in 2003 in
      Taiwan. In this perspective, we present the construction of the NIIS and two
      innovative applications, which were implemented in 2009, which link the NIIS with
      other databases for better control of measles. Firstly, by linking the NIIS with
      hospital administrative records, we are able to follow up contacts of measles
      cases in a timely manner to provide the necessary prophylaxis, such as
      immunoglobulin or vaccines. Since 2009, there have been no measles outbreaks in
      hospitals in Taiwan. Secondly, by linking the NIIS with an immigration database,
      we are able to ensure that young citizens under the age of five years entering
      Taiwan from abroad become fully vaccinated. Since 2009, the measles-mumps-rubella
      vaccine coverage rate at two years of age has increased from 96% to 98%. We
      consider these applications of the NIIS to be effective mechanisms for improving
      the performance of infectious disease control in Taiwan. The experience gained
      could provide a valuable example for other countries.

PMID- 25597543
TI  - Letter to the editor: management of patients with Ebola virus disease in Europe:
      high-level isolation units should have a key role.

PMID- 25597544
TI  - Authors reply: management of patients with Ebola virus disease in Europe: high
      level isolation units should have a key role.

PMID- 25597547
TI  - Anion transport through lipids in a hybrid bilayer membrane.
AB  - In this report, we use a hybrid bilayer membrane (HBM) as an electrochemical
      platform to study anion diffusion through a lipid monolayer. We first append
      lipid on a self-assembled monolayer (SAM) that contains a covalently bound
      Cu(I)/Cu(II) redox center. We then perform cyclic voltammetry (CV) using
      different anions in bulk solution and extract thermodynamic and kinetic
      information about anion transport. We analyze the results using linear
      combinations of fundamental chemical trends and determine that anion transport
      quantitatively correlates to polarity and basicity, a relationship we formalize
      as the lipid permeability parameter. In addition, we discuss how our findings can
      be interpreted according to the two leading mechanisms describing ion
      permeability through lipids. Our results demonstrate that anion transport in a
      HBM is best described by the solubility-diffusion mechanism, not the pore
      mechanism. 

PMID- 25597548
TI  - Use of multi-dose activated charcoal in phenytoin toxicity secondary to genetic
      polymorphism.
AB  - INTRODUCTION: Phenytoin is metabolised in the liver by cytochrome (CYP)2C9 and
      2C19 enzymes. Due to saturation of enzyme capacity, the elimination half-life is
      prolonged at supratherapeutic levels. Genetic polymorphisms of CYP2C9 and 2C19
      are reasonably common and further prolong the elimination of phenytoin. There are
      conflicting reports regarding whether multiple-dose activated charcoal (MDAC)
      significantly increases the clearance of phenytoin in poisoning. CASE REPORT: We
      present 3 patients with phenytoin toxicity and very slow elimination secondary to
      reduced CYP enzyme function from genetic polymorphisms. MDAC was used in two
      patients and led to rapid and large reductions in the measured elimination half
      lives. This is contrasted with very prolonged elimination in a third patient who
      did not receive MDAC. CONCLUSION: MDAC may play a role in the management of
      chronic phenytoin toxicity, especially in those with very slow endogenous
      elimination secondary to genetic polymorphisms.

PMID- 25597549
TI  - Cycloplegic refraction is the gold standard for epidemiological studies.
AB  - Many studies on children have shown that lack of cycloplegia is associated with
      slight overestimation of myopia and marked errors in estimates of the prevalence
      of emmetropia and hyperopia. Non-cycloplegic refraction is particularly
      problematic for studies of associations with risk factors. The consensus around
      the importance of cycloplegia in children left undefined at what age, if any,
      cycloplegia became unnecessary. It was often implicitly assumed that cycloplegia
      is not necessary beyond childhood or early adulthood, and thus, the protocol for
      the classical studies of refraction in older adults did not include cycloplegia.
      Now that population studies of refractive error are beginning to fill the gap
      between schoolchildren and older adults, whether cycloplegia is required for
      measuring refractive error in this age range, needs to be defined. Data from the
      Tehran Eye Study show that, without cycloplegia, there are errors in the
      estimation of myopia, emmetropia and hyperopia in the age range 20-50, just as in
      children. Similar results have been reported in an analysis of data from the
      Beaver Dam Offspring Eye Study. If the only important outcome measure of a
      particular study is the prevalence of myopia, then cycloplegia may not be crucial
      in some cases. But, without cycloplegia, measurements of other refractive
      categories as well as spherical equivalent are unreliable. In summary, the
      current evidence suggests that cycloplegic refraction should be considered as the
      gold standard for epidemiological studies of refraction, not only in children,
      but in adults up to the age of 50.

PMID- 25597545
TI  - Nitric oxide stimulates matrix synthesis and deposition by adult human aortic
      smooth muscle cells within three-dimensional cocultures.
AB  - Vascular diseases are characterized by the over-proliferation and migration of
      aortic smooth muscle cells (SMCs), and degradation of extracellular matrix (ECM)
      within the vessel wall, leading to compromise in cell-cell and cell-matrix
      signaling pathways. Tissue engineering approaches to regulate SMC over
      proliferation and enhance healthy ECM synthesis showed promise, but resulted in
      low crosslinking efficiency. Here, we report the benefits of exogenous nitric
      oxide (NO) cues, delivered from S-Nitrosoglutathione (GSNO), to cell
      proliferation and matrix deposition by adult human aortic SMCs (HA-SMCs) within
      three-dimensional (3D) biomimetic cocultures. A coculture platform with two
      adjacent, permeable 3D culture chambers was developed to enable paracrine
      signaling between vascular cells. HA-SMCs were cultured in these chambers within
      collagen hydrogels, either alone or in the presence of human aortic endothelial
      cells (HA-ECs) cocultures, and exogenously supplemented with varying GSNO dosages
      (0-100 nM) for 21 days. Results showed that EC cocultures stimulated SMC
      proliferation within GSNO-free cultures. With increasing GSNO concentration, HA
      SMC proliferation decreased in the presence or absence of EC cocultures, while HA
      EC proliferation increased. GSNO (100 nM) significantly enhanced the protein
      amounts synthesized by HA-SMCs, in the presence or absence of EC cocultures,
      while lower dosages (1-10 nM) offered marginal benefits. Multi-fold increases in
      the synthesis and deposition of elastin, glycosaminoglycans, hyaluronic acid, and
      lysyl oxidase crosslinking enzyme (LOX) were noted at higher GSNO dosages, and
      coculturing with ECs significantly furthered these trends. Similar increases in
      TIMP-1 and MMP-9 levels were noted within cocultures with increasing GSNO
      dosages. Such increases in matrix synthesis correlated with NO-stimulated
      increases in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide
      synthase (iNOS) expression within EC and SMC cultures, respectively. Results
      attest to the benefits of delivering NO cues to suppress SMC proliferation and
      promote robust ECM synthesis and deposition by adult human SMCs, with significant
      applications in tissue engineering, biomaterial scaffold development, and drug
      delivery. 

PMID- 25597550
TI  - Verification of the biomarker candidates for non-small-cell lung cancer using a
      targeted proteomics approach.
AB  - Lung cancer, with its high metastatic potential and high mortality rate, is the
      worldwide leading cause of cancer-related deaths. High-throughput "omics"-based
      platforms have accelerated the discovery of biomarkers for lung cancer, and the
      resulting candidates are to be evaluated for their diagnostic potential as
      noninvasive biomarkers. The evaluation of the biomarker candidates involves the
      quantitative measurement of large numbers of proteins in bodily fluids using
      advanced mass spectrometric techniques. In this study, a robust pipeline based on
      targeted proteomics was developed for biomarker verification in plasma samples
      and applied to verifying lung cancer biomarker candidates. Highly multiplexed
      liquid chromatrography-selected reaction monitoring (LC-SRM) assays for 95
      potential tumor markers for non-small-cell lung cancer (NSCLC) were generated to
      screen plasma samples obtained from 72, early to late stage, patients. A total of
      17 proteins were verified as potent tumor markers detectable in plasma and, where
      available, verified by enzyme-linked immunosorbent assays (ELISAs). A novel
      plasma-based biomarker, zyxin, fulfilled the criteria for a potential early
      diagnostic marker for NSCLC. 

PMID- 25597551
TI  - Novel homozygous deletion of segmental KAL1 and entire STS cause Kallmann
      syndrome and X-linked ichthyosis in a Chinese family.
AB  - Kallmann syndrome (KS) is a genetically heterogeneous disease characterised by
      hypogonadotrophic hypogonadism in association with anosmia or hyposmia. This
      condition affects 1 in 10 000 men and 1 in 50,000 women. Defects in seventeen
      genes including KAL1 gene contribute to the molecular basis of KS. We report the
      clinical characteristics, molecular causes and treatment outcome of two Chinese
      brothers with KS and X-linked ichthyosis. The phenotypes of the patients were
      characterised by bilateral cryptorchidism, unilateral renal agenesis in one
      patient but normal kidney development in another. The patients had low serum
      testosterone, follicle-stimulating hormone and luteinising hormone levels and a
      blunt response to the gonadotrophin-releasing hormone stimulation test. After
      human chorionic gonadotrophin treatment, the serum testosterone levels were
      normalized, and the pubic hair, penis length and testicular volumes were greatly
      improved in both of the patients. The two affected siblings had the same novel
      deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene. Our
      study broadens the mutation spectrum in the KAL1 gene associated with KS and
      facilitates the genetic diagnosis and counselling for KS.

PMID- 25597552
TI  - An investigation of the efficiency of the mini-Kingston standardized cognitive
      assessment-revised in classifying patients according to DSM-5 major and mild
      neurocognitive disorders due to possible Alzheimer's disease.
AB  - BACKGROUND: The aim of this study was to examine the efficiency of the mini
      Kingston standardized cognitive assessment-revised (mini-KSCAr) in classifying
      patients according to DSM-5 major and mild neurocognitive disorders (NCD) due to
      possible Alzheimer's disease (AD). METHODS: Files of 85 individuals who were
      tested on the Kingston standardized cognitive assessment-revised were reviewed
      and scores were calculated for the mini-KSCAr. Medical history, psychiatric and
      physical status, basic and instrumental activities of daily living, as well as
      scores on the Cambridge cognitive examination-revised (CAMCOG-R), and the
      clinical dementia rating (CDR) scale were used to establish DSM-5 diagnoses of
      major or mild neurocognitive disorders (NCD) due to possible AD or no cognitive
      decline. All participants were tested on the Mini-Mental State Examination (MMSE)
      and the clock drawing test (CDT), and a subset (N = 28) were also tested on three
      well-known memory tasks. RESULTS: Scores on the MMSE, CDT, and mini-KSCAr
      differed across groups, but only the mini-KSCAr significantly distinguished each
      group from the other two. The mini-KSCAr showed better sensitivity, specificity,
      and likelihood ratios (LRs) than did the MMSE and the CDT. A regression analysis
      revealed that the mini-KSCAr accounted for almost half of the variance in memory
      performance, whereas the MMSE and the CDT contributed nothing to this prediction
      once the mini-KSCAr was used. CONCLUSIONS: The mini-KSCAr is an efficient
      instrument for the diagnosis of DSM-5 major and mild NCD due to possible AD in a
      specialized psychogeriatric setting, and its utility is greater than that of the
      MMSE and the CDT.

PMID- 25597553
TI  - Biodegradable vancomycin-eluting poly[(d,l)-lactide-co-glycolide] nanofibres for
      the treatment of postoperative central nervous system infection.
AB  - The incidence of postoperative central nervous system infection (PCNSI) is higher
      than 5%-7%. Successful management of PCNSI requires a combined therapy of
      surgical debridement and long-term antibiotic treatment. In this study, Duraform
      soaked in a prepared bacterial solution was placed on the brain surface of rats
      to induce PCNSI. Virgin poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous
      membranes (vehicle-control group) and vancomycin-eluting PLGA membranes
      (vancomycin-nanofibres group) were implanted. The wound conditions were observed
      and serial brain MRI and pathology examinations were performed regularly. PCNSI
      was consistently induced in a single, simple step. In the vehicle-control group,
      most rats died within 1 week, and the survival rate was low (odds ratio = 0.0357,
      95% confidence interval = 0.0057-0.2254). The wounds and affected cerebral
      tissues necrosed with purulence and increased in mass from the resulting PCNSI
      volumes. Initially, the mean PCNSI volumes showed no significant difference
      between the two groups. The PCNSI volume in the rats in the vancomycin-nanofibres
      group significantly decreased (P < 0.01), and the wound appearance was excellent.
      Pathologic examinations revealed that the necrosis and leukocyte infiltration
      area decreased considerably. The experimental results suggest that vancomycin
      eluting PLGA nanofibres are favourable candidates for treating PCNSI after
      surgical debridement. 

PMID- 25597554
TI  - Depressive symptoms, cardiovascular disease severity, and functional status in
      older adults with coronary heart disease: the heart and soul study.
AB  - OBJECTIVES: To compare the contributions of depressive symptoms and
      cardiovascular disease (CVD) severity to functional decline in individuals with
      coronary heart disease. DESIGN: Longitudinal. SETTING: Twelve outpatient clinics
      in the San Francisco Bay area. PARTICIPANTS: Older adults (N = 960; mean age 67)
      with stable coronary heart disease recruited between September 2000 and December
      2002. MEASUREMENTS: At baseline, depressive symptoms and angina pectoris were
      assessed according to self-report, and left ventricular ejection fraction (LVEF)
      and exercise capacity were evaluated using echocardiography and exercise
      treadmill testing. Difficulty performing activities of daily living and
      instrumental activities of daily living was assessed at baseline and annually for
      the next 5 years. Covariates included demographic characteristics, comorbid
      conditions, cognitive function, social support, and health behaviors. Five years
      later, 658 participants returned for follow-up assessments. RESULTS: Higher
      baseline depressive symptoms predicted greater risk of functional decline over 5
      years, whereas higher baseline exercise capacity was associated with lower risk
      of functional decline. In 658 participants who returned for follow-up, 5-year
      changes in depressive symptoms and exercise capacity were associated with 5-year
      changes in functional status. Angina pectoris frequency and LVEF were not
      associated with functional decline or change in functional status, after
      adjusting for covariates and other predictors. CONCLUSION: In older adults with
      coronary heart disease, depressive symptoms and lower exercise capacity predicted
      functional decline over 5 years. In contrast, other traditional measures of CVD
      severity (LVEF and angina pectoris) were not independently predictive of
      subsequent functional status. These findings suggest that efforts to ameliorate
      depressive symptoms may be as important as treating CVD severity to enhance
      functional status.

PMID- 25597555
TI  - Impaired olfaction and risk of delirium or cognitive decline after cardiac
      surgery.
AB  - OBJECTIVES: To determine the prevalence of impaired olfaction in individuals
      presenting for cardiac surgery and the independent association between impaired
      olfaction and postoperative delirium and cognitive decline. DESIGN: Nested
      prospective cohort study. SETTING: Academic hospital. PARTICIPANTS: Individuals
      undergoing coronary artery bypass, valve surgery, or both (n = 165).
      MEASUREMENTS: Olfaction was measured using the Brief Smell Identification Test,
      with impaired olfaction defined as an olfactory score below the fifth percentile
      of normative data. Delirium was assessed using a validated chart review method.
      Cognitive performance was assessed using a neuropsychological testing battery at
      baseline and 4 to 6 weeks after surgery. RESULTS: Impaired olfaction was
      identified in 54 of 165 participants (33%) before surgery. Impaired olfaction was
      associated with greater adjusted risk of postoperative delirium (relative risk =
      1.90, 95% confidence interval = 1.17-3.09, P = .009). There was no association
      between impaired olfaction and change in composite cognitive score in the overall
      study population. CONCLUSION: Impaired olfaction is prevalent in individuals
      undergoing cardiac surgery and is associated with greater adjusted risk of
      postoperative delirium but not cognitive decline. Impaired olfaction may identify
      unrecognized vulnerability to postoperative delirium in individuals undergoing
      cardiac surgery.

PMID- 25597556
TI  - Factors that affect quality of life from the perspective of people with dementia:
      a metasynthesis.
AB  - OBJECTIVES: To comprehensively and systematically identify, appraise, and
      synthesize qualitative research findings on factors that affect quality of life
      from the perspective of people with dementia. DESIGN: Systematic review and
      metasynthesis of primary qualitative studies in published and gray literature
      that aimed to identify factors that influence quality of life from the
      perspective of people with dementia. Expert-developed search strategies were
      applied in nine electronic databases. Reference lists of included articles and
      literature reviews identified during the search were reviewed. Structured
      inclusion criteria were applied to screen 5,625 titles and abstracts to identify
      11 qualitative studies published from 1975 to April 2012. Two independent
      reviewers appraised study quality. SETTING: Primary study recruitment sites
      included long-term care and community-based settings in the United Kingdom, the
      United States, Canada, the Netherlands, Ireland, Australia, and Japan.
      PARTICIPANTS: A combined sample of 345 people with mild, moderate, and severe
      dementia. MEASUREMENTS: The primary studies used interview and focus group
      methods. Findings from primary studies were synthesized using techniques of
      taxonomic analysis, constant comparison, and importing concepts. RESULTS: Four
      factors and the experience of connectedness or disconnectedness within each
      factor influenced quality of life according to people with dementia. These
      factors, and the terms that represent connectedness and disconnectedness, were
      relationships (together vs alone), agency in life today (purposeful vs aimless),
      wellness perspective (well vs ill), and sense of place (located vs unsettled).
      Happiness and sadness were key outcomes of good and poor quality of life,
      respectively. CONCLUSION: The four factors identified potentially modifiable
      areas to improve quality of life for people with dementia, even in the context of
      worsening cognitive function.

PMID- 25597557
TI  - Hospital-associated functional decline: the role of hospitalization processes
      beyond individual risk factors.
AB  - OBJECTIVES: To investigate the combined contribution of processes of
      hospitalization and preadmission individual risk factors in explaining functional
      decline at discharge and at 1-month follow-up in older adults with nondisabling
      conditions. DESIGN: Prospective cohort study. SETTING: Internal medicine wards in
      two Israeli medical centers. PARTICIPANTS: Six hundred eighty-four individuals
      aged 70 and older admitted for a nondisabling problem. MEASUREMENTS: Functional
      decline was measured according to change in modified Barthel Index from premorbid
      to discharge and from premorbid to 1 month after discharge. In-hospital mobility,
      continence care, sleep medication consumption, satisfaction with hospital
      environment, and nutrition intake were assessed using previously tested self
      report instruments. RESULTS: Two hundred eighty-two participants (41.2%) reported
      functional decline at discharge and 317 (46.3%) at 1 month after discharge. Path
      analysis indicated that in-hospital mobility (standardized maximum likelihood
      estimate (SMLE) = -0.48, P < .001), continence care (SMLE = -0.12, P < .001), and
      length of stay (LOS) (SMLE = 0.06, P < .001) were directly related to functional
      decline at discharge and, together with personal risk factors, explained 64% of
      variance. In-hospital mobility, continence care, and LOS were indirectly related
      to functional decline at 1 month after discharge through functional decline at
      discharge (SMLE = 0.45, P < .001). Nutrition consumption (SMLE = -0.07, P < .001)
      was significantly related to functional decline at 1 month after discharge,
      explaining, together with other risk factors, 32% of variance. CONCLUSION: In
      hospital low mobility, suboptimal continence care, and poor nutrition account for
      immediate and 1-month posthospitalization functional decline. These are
      potentially modifiable hospitalization risk factors for which practice and policy
      should be targeted in efforts to curb the posthospitalization functional decline
      trajectory.

PMID- 25597558
TI  - Effect of a falls quality improvement program on serious fall-related injuries.
AB  - OBJECTIVES: To determine whether a program that improves the quality of care for
      falls reduces the number of episodes of care for serious fall-related injuries.
      DESIGN: Nonrandomized controlled trial. SETTING: Four community-based primary
      care practices. PARTICIPANTS: Individuals aged 75 and older who screened positive
      for fall risk. INTERVENTION: A multicomponent quality improvement program
      (Assessing Care of Vulnerable Elders Practice Redesign for Improved Medical Care
      for Elders) involving face-to-face clinician education about falls and decision
      support to prompt primary care providers to implement appropriate care, including
      referral to appropriate community resources, in response to individuals screening
      positive for fall risk. MEASUREMENTS: Episodes of care for selected fall-related
      injuries, based on healthcare claims. RESULTS: Of 1,791 individuals with data
      available for analysis, 1,187 were in the intervention group, and 604 were in the
      control group. Mean age was 83, and more than two-thirds of the sample were
      women. After adjusting for potential confounders, there were no statistically
      significant differences between intervention and control groups in episodes of
      care for fall-related injuries during the 12-month (incidence rate ratio (IRR)
      1.27, 95% confidence interval (CI) = 0.93-1.73) or 24-month (IRR 1.18, 95% CI =
      0.93-1.49) period after initiation of the intervention. CONCLUSION: Despite
      improving the care of falls, this quality improvement initiative did not result
      in a change in the number of episodes of care for serious fall-related injuries.
      Future work in community-based settings should test higher-intensity
      interventions to reduce fall-related injuries.

PMID- 25597559
TI  - Underuse of oral anticoagulation for individuals with atrial fibrillation in a
      nursing home setting in France: comparisons of resident characteristics and
      physician attitude.
AB  - OBJECTIVES: To describe the characteristics of nursing home residents diagnosed
      with atrial fibrillation (AF) and eligible for oral anticoagulants who did not
      receive these drugs and to detail the conditions that physicians who decide not
      to prescribe anticoagulants take into account. DESIGN: Cross-sectional. SETTING:
      Nursing home. PARTICIPANTS: Nursing home residents with a history of AF (N =
      1,085). MEASUREMENTS: Data were collected on clinical characteristics, geriatric
      syndromes, and antithrombotic regimen. Multivariate logistic regression was used
      to identify factors associated with nonprescription of anticoagulants. A
      standardized questionnaire was submitted to physicians in charge of patients with
      AF, to detail conditions associated with their medical decision not to prescribe
      anticoagulants. RESULTS: History of AF was present in 1,085 nursing home
      residents (10.1%), mean age 87, with a mean CHA2DS2-VASc score of 5.1 +/- 1.4. Of
      these residents with AF, 544 (50.1%) did not receive anticoagulants. Recurrent
      falls (odds ratio (OR) = 4.9, 95% confidence interval (CI) = 2.4-9.9, P < .001),
      past history of bleeding (OR = 3.62, 95% CI = 1.54-8.51, P = .003), paroxysmal AF
      (OR = 3.5, 95% CI = 1.83-6.66, P < .001), and advanced age (OR = 1.1, 95% CI =
      1.01-1.17, P = .02) were significantly associated with not prescribing
      anticoagulants. Recurrent falls (47%), cognitive impairment (22.6%), and advanced
      age (16.4%) were the main reasons for not prescribing anticoagulants. CONCLUSION:
      The prevalence of AF in a cohort of very old nursing home residents was 10%.
      Anticoagulation was prescribed in fewer than 50% of eligible cases despite high
      individual risk of stroke. Geriatric syndromes, especially falls and cognitive
      disorders, were the main reported contraindications for prescribing
      anticoagulants. Physicians caring for those residents wrongly thought that
      paroxysmal AF caused fewer thromboembolic events than permanent AF, which
      explains lower rates of anticoagulant prescription in individuals with paroxysmal
      AF.

PMID- 25597560
TI  - Comparison of anticholinergic risk scales and associations with adverse health
      outcomes in older people.
AB  - OBJECTIVES: To investigate whether anticholinergic burden scores from nine
      published anticholinergic scales are associated with adverse health outcomes,
      including hospital admissions, hospitalizations for falls, hospital length of
      stay (LOS), and more visits to general practitioners (GPs). DESIGN:
      Pharmacoepidemiological population-based study. SETTING: New Zealand.
      PARTICIPANTS: Population aged 65 and older (n = 537,387). MEASUREMENTS: Data were
      analyzed for 537,387 individuals from the Pharmaceutical Claims Data Mart data
      set (2011). Anticholinergic medication exposure was calculated using nine
      published scales. Events information (2012) was extracted from the National
      Minimum Datasets using International Classification of Diseases, Tenth Revision,
      codes. Predictors of hospital admissions, hospitalizations for falls, LOS, and GP
      visits were examined using regression models adjusting for age, sex, ethnicity,
      comorbidities, and polypharmacy. RESULTS: Prevalence of exposure to
      anticholinergic medicines ranged from 22.8% to 55.9% according to the different
      scales. Multivariate regression analysis showed that anticholinergic burden
      scores quantified according to all nine scales were significantly associated with
      hospital admissions, hospitalizations for falls, LOS, and GP visits (P < .001).
      The strongest predictors of these outcomes were the Drug Burden Index
      Anticholinergic component scores, aged 85 and older, female sex, and
      polypharmacy. CONCLUSION: There are substantial differences in the estimation of
      anticholinergic burden exposure between the nine scales. Anticholinergic burden
      scores obtained from each of the scales were associated with adverse clinical
      outcomes of interest.

PMID- 25597561
TI  - Associations between oral health and risk of dementia in a 37-year follow-up
      study: the prospective population study of women in Gothenburg.
AB  - OBJECTIVES: To investigate the association between incident dementia and previous
      number of teeth measured over a long interval. DESIGN: Retrospective analysis of
      a 37-year cohort study. SETTING: Prospective Population Study of Women in
      Gothenburg. PARTICIPANTS: Women with (n = 158) and without (n = 539) dementia in
      2000 to 2005. MEASUREMENTS: Tooth counts in 1968-69, 1980-81, and 1992-93.
      Covariates included age, education, stroke, myocardial infarction, diabetes
      mellitus, smoking status, blood pressure, body mass index, and cholesterol level.
      RESULTS: After adjustment for age, odds ratios (ORs) for dementia in 2000-05,
      comparing first with fourth tooth count quartiles, were 1.81 (95% confidence
      interval (CI) = 1.03-3.19) for tooth counts measured in 1968, 2.25 (95% CI = 1.18
      4.32) for those in 1980, and 1.99 (0.92-4.30) for those in 1992. After further
      adjustment for education, ORs were 1.40 (95% CI = 1.03-3.19) for 1968, 1.96 (95%
      CI = 0.98-3.95) for 1980, and 1.59 (95% CI = 0.71-3.53) for 1992, and after
      additional adjustment for vascular risk factors, ORs were 1.38 (95% CI = 0.74
      2.58) for 1968, 2.09 (95% CI = 1.01-4.32) for 1980, and 1.61 (95% CI = 0.70-3.68)
      for 1992. CONCLUSION: In most of the analyses, lower tooth count was not
      associated with dementia, although a significant association was found for one of
      the three examinations. Further research may benefit from more-direct measures of
      dental and periodontal disease.

PMID- 25597562
TI  - Frailty prevalence and neighborhood residence in older Mexican Americans: the San
      Antonio longitudinal study of aging.
AB  - OBJECTIVES: To examine the association between neighborhood residence and frailty
      prevalence in older Mexican Americans (MAs). DESIGN: Cross-sectional,
      observational study. SETTING: Socioeconomically and ethnically diverse
      neighborhoods in San Antonio, Texas. PARTICIPANTS: Community-dwelling older MA
      adults (aged >= 65) who completed the baseline examination of the San Antonio
      Longitudinal Study of Aging (SALSA) (1992-1996) (N = 394). MEASUREMENTS: Subjects
      were randomly sampled from three types of neighborhoods that varied in ethnic
      composition and economic environment: barrio (low-income, exclusively MA),
      transitional (middle-income, equal proportion MAs and European Americans (EAs))
      and suburban (upper-income, predominantly EA). Frailty was classified using the
      Fried criteria. Frailty odds were estimated according to neighborhood using
      logistic regression, with the suburban neighborhood as the reference category.
      Covariates included age, sex, diseases, depressive symptoms, and cognitive
      function. RESULTS: Frailty prevalence was 15.6% in the barrio, 9.4% in the
      transitional neighborhood, and 3.5% in the suburbs (P = .01). After adjusting for
      sociodemographic characteristics and disease covariates, odds of frailty were
      4.15 times as high for MAs residing in the barrio as for those residing in the
      suburbs (P = .03). After adjustment for depression and cognition, this
      association was no longer significant. Diabetes mellitus and depression accounted
      for the higher odds of frailty in the barrio. Although odds of frailty in the
      transitional neighborhood were 1.95 times as high as those in the suburbs, the
      difference was not statistically significant. CONCLUSION: The ethnic composition
      and economic environment of the neighborhoods in which MA older adults reside are
      strongly associated with their odds of being frail.

PMID- 25597563
TI  - Lower blood pressure and apathy coincide in older persons with poorer functional
      ability: the Discontinuation of Antihypertensive Treatment in Elderly People
      (DANTE) Study Leiden.
AB  - OBJECTIVES: To examine the association between blood pressure (BP) measures and
      symptoms of apathy and depression in older adults with various levels of
      functional ability. DESIGN: Cross-sectional study using baseline data from the
      Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study
      Leiden. SETTING: Primary care setting, the Netherlands. PARTICIPANTS: Community
      dwelling individuals aged 75 and older (N = 430). MEASUREMENTS: Systolic BP
      (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were measured during
      home visits. Symptoms of apathy and depression were assessed using the Apathy
      Scale and the Geriatric Depression Scale (GDS-15), respectively. Stratified
      linear regression was performed in participants with better and worse functional
      ability according to the median of the Groningen Activity Restriction Scale.
      RESULTS: In participants with lower functional ability, each 10-mmHg lower SBP,
      DBP, and MAP was associated with higher Apathy Scale scores (0.63, 0.92, and 0.94
      points, respectively, all P < .005) but not with GDS-15 scores. In participants
      with higher functional ability, BP measures were not associated with Apathy Scale
      or GDS-15 scores. CONCLUSION: In older participants with poorer functional
      ability, lower BP was associated with more symptoms of apathy but not depression.

PMID- 25597564
TI  - Comparative study of four physical performance measures as predictors of death,
      incident disability, and falls in unselected older persons: the insufficienza
      Cardiaca negli Anziani Residenti a Dicomano Study.
AB  - OBJECTIVES: To compare the ability of the Short Physical Performance Battery
      (SPPB), 4-m walk test (4mWT), 6-minute walk test (6MWT), and handgrip strength to
      predict mortality, incident disability, worsening mobility, and falls in older
      community dwellers. DESIGN: Cohort study. SETTING: Population-based.
      PARTICIPANTS: Individuals aged 65 and older n = 561) without prevalent basic
      activity of daily living (ADL) disability participating. MEASUREMENTS: Separate
      logistic regression models were developed to predict incident ADL disability,
      worsening mobility, and falls in 3 years, and Cox regression models were used to
      assess 7-year risk of death as a function of the four tests, adjusting for
      covariates. RESULTS: Performance tests were reciprocally correlated at baseline.
      After 3 years, 33 (7.3%) of 453 participants reexamined were disabled in ADLs, 87
      (20%) had worsening mobility, and 99 (22%) reported falls. Of the 561 baseline
      participants, 141 (25%) died over the 7 years. All measures predicted incident
      ADL disability, with adjusted odds ratios (ORs) per unit increase of 0.85 (95%
      confidence interval (CI) = 0.77-0.93) for handgrip strength, 0.08 (95% CI = 0.02
      0.36) for 4mWT, 0.74 (95% CI = 0.61-0.89) for SPPB, and 0.993 (95% CI = 0.988
      0.997) for 6MWT. Handgrip strength (OR = 0.88, 95% CI = 0.83-0.93), 4mWT (OR =
      0.33, 95% CI = 0.11-0.94), and SPPB (OR = 0.81, 95%CI = 0.71-0.93) predicted
      worsening mobility. No measure predicted falls; only SPPB (hazard ratio (HR) =
      0.92, 95% CI = 0.85-0.997) and 6MWT (HR = 0.997, 95% CI = 0.995-0.999) predicted
      death. CONCLUSION: Performance measures are independent predictors of relevant
      health outcomes, with the exception of falls. Because SPPB is easily applied and
      is the only measure predicting incident ADL disability, worsening mobility, and
      death, it is preferable to the other tests.

PMID- 25597565
TI  - Mammography screening for women aged 70 and older: at a crossroads.

PMID- 25597566
TI  - Coordinated care of medically complex individuals in an individual-centered
      medical home: the surprising case of Mr. and Mrs. W.

PMID- 25597567
TI  - Cinderella's lifetime abuse.

PMID- 25597568
TI  - Effects of Tai Chi ball on balance and physical function in older adults with
      type 2 diabetes mellitus.

PMID- 25597569
TI  - Physical fitness and sociocognitive engagement are associated with different
      aspects of cognition in older adults.

PMID- 25597570
TI  - Proton pump inhibitors and hypomagnesemia in polymorbid elderly adults.

PMID- 25597571
TI  - Insight into elder abuse among urban poor of Kuala Lumpur, Malaysia-a middle
      income developing country.

PMID- 25597572
TI  - Lower glomerular filtration rate associated with white matter hyperintensities
      more in vascular dementia than in Alzheimer's disease.

PMID- 25597573
TI  - Cessation of driving is rare in older drivers seen in the emergency department
      after a motor vehicle collision: a prospective cohort study.

PMID- 25597575
TI  - Development of an age-dependent antibiogram in a Veterans Affairs community.

PMID- 25597574
TI  - Association between potentially inappropriate medication use in elderly adults
      and hospital-related outcomes.

PMID- 25597576
TI  - Cutaneous surgery complications in individuals aged 80 and older versus younger
      than 80 after excision of nonmelanoma skin cancer.

PMID- 25597577
TI  - Effect of early diagnosis and lifestyle modification on functional activities in
      community-dwelling elderly adults with glucose intolerance: 5-year longitudinal
      study.

PMID- 25597578
TI  - High prevalence of undiagnosed eye diseases in individuals with dementia.

PMID- 25597579
TI  - Online administration of a quantified self-questionnaire for elderly people: a
      user satisfaction survey.

PMID- 25597580
TI  - The need for uniform quality reporting across post-acute care rehabilitation
      settings: an examination of accidental falls.

PMID- 25597581
TI  - Persistent dizziness.

PMID- 25597582
TI  - Sarcoidosis presenting as late-onset dementia: are cerebrospinal fluid biomarkers
      analyses helpful?

PMID- 25597583
TI  - Hidden in a headache: cryptococcal meningitis in a septuagenarian.

PMID- 25597584
TI  - Delayed discovery and diagnosis of achalasia resulting in megaesophagus in an
      elderly nursing home resident.

PMID- 25597585
TI  - Coherent patients and good outcomes.

PMID- 25597586
TI  - Response to Thomas E. Finucane, MD.

PMID- 25597587
TI  - Learning from experience and making plans?

PMID- 25597588
TI  - Televideo clock drawing test to reach rural Veterans: feasibility in community
      based outpatient clinics in the department of Veterans Affairs.

PMID- 25597589
TI  - Testosterone levels and bone mineral density in healthy elderly men.

PMID- 25597590
TI  - Establishing code status: are people's decisions truly informed?

PMID- 25597591
TI  - Morley-JAGS link to perspectives of geriatrics paper.

PMID- 25597592
TI  - Individualized antithrombotic therapy.
AB  - Clot formation in the circulation is a physiological mechanism preventing
      bleeding at sites of loss of vascular integrity. Clot formation may also occur
      intravascularly under pathological conditions, e.g. leading to myocardial
      infarction, stroke, and critical limb ischaemia. Clot formation involves
      activation of the coagulation cascade and of platelets eventually leading to an
      occlusive clot. In the venous circulation, clots are rich in erythrocytes and
      fibrin, while in the arterial circulation platelets predominate. Accordingly,
      drugs have been developed to interfere with the activation of the coagulation
      and/or platelets. As several coagulation factors such as factor VII, VIIII, X and
      thrombin (factor II) are vitamin K-dependent, drugs interfering with the effects
      of the vitamin (VKAs), i.e. warfarin, marcoumar or sintrom have been used for
      decades to prevent thromboembolism and embolic stroke. With the advent of
      selective inhibitors of factor X (apixaban, edoxaban and rivaroxaban) or factor
      II (dabigratan) the therapeutic spectrum of anti-thrombotic therapy has been
      expanded. On the other hand, platelet inhibitors such as aspirin and
      thienopyridines, i.e. clopidogrel, prasugrel, and ticagrelor have extensively
      been used to treat arterial disease in the coronary, cerebrovascular and
      peripheral circulation. Individualized antithrombotic therapy considers (1)
      characteristics of the disease and (2) those of the patient. Such a decision tree
      first separates "arterial" and "venous" thrombi. For the prevention of arterial
      thrombi that occur in acute myocardial infarction and certain forms of stroke and
      critical limb ischemia, platelet inhibitors are indicated. The first line drug is
      aspirin which interferes with thromboxane A2 (TXA2) formation and partially
      inhibits platelet activation. In patients receiving a stent or in acute coronary
      syndromes (ACS), the combination of aspirin with a thienopyridine is indicated.
      On the other hand, patients with venous clots should be treated with
      anticoagulants interfering with the activation of the coagulation cascade. While
      the longest experiences exist with vitamin K antagonists, the novel oral
      anticoagulants (NOACs) are at least as effective, but associated with less
      intracerebral and life-threatening bleeding. VKAs remain the treatment of choice
      in patients receiving artificial heart valves or with renal failure (in general a
      GFR of 30 ml/min/KG or less). In the remaining patients, current evidence
      suggests that NOACs should be preferred. The NOACs are well documented in
      patients with thromboembolism and atrial fibrillation. Whether patients with an
      acute ACS should receive dual antiplatelet drugs plus a low dose NOAC is a matter
      of debate, although conceptually it is an attractive concept. In patients after
      stent implantation with atrial fibrillation, in which a triple therapy with dual
      antiplatelet drugs and an anticoagulant is indicated, bleeding is an issue.
      Recent data suggest that administering a thienopyridine plus warfarin (or
      possibly a NOAC), while at the same time skipping aspirin may be an alternative
      to avoid severe bleeding and to maintain antithrombotic efficacy. CONCLUSION: An
      extensive therapeutic arsenal to interfere with clot formation requires an
      individualized approach considering the disease condition and co-morbidities of
      the patient, the anticoagulants' and patient characteristics. This review builds
      on and extends previous publications of the authors on this topic.

PMID- 25597594
TI  - Relationship between balance and dual task walking in the very elderly.
AB  - AIM: To investigate the relationship between balance and dual task performance in
      adults aged over 80 years, and to analyze possible differences between fallers
      and non-fallers in dual task performance. METHODS: An observational cross
      sectional study was carried out at the Federal University of Sao Carlos (Brazil).
      We assessed 67 community-dwelling older adults aged over 80 years who were able
      to walk. The volunteers were divided into groups of fallers and non-fallers. The
      one-leg standing and tandem tests were used to assess balance. Dual task was
      assessed by the Timed Up and Go test, associated with a motor task (TUGT-motor)
      and a cognitive task (TUGT-cognitive). Statistical analyses were carried out, and
      the significance level was set at alpha = 5%. RESULTS: Significant correlations
      were found between balance and dual task variables. Fallers took significantly
      more time and steps on both the TUGT-motor and the TUGT-cognitive, with no
      significant differences on balance tests between groups. CONCLUSIONS: Recognizing
      the influence of dual task walking on balance and fall risk could help health
      professionals to prevent falls in older adults, as well as optimize assessment
      and intervention planning.

PMID- 25597593
TI  - alpha- L-iduronidase gene-based therapy using the phiC31 system to treat
      mucopolysaccharidose type I mice.
AB  - BACKGROUND: Mucopolysaccharidose type I (MPSI) is a lysosomal monogenic disease
      caused by mutations in the gene for alpha- L-iduronidase (IDUA). MPSI patients
      need a constant supply of IDUA to alleviate progression of the disease. IDUA gene
      transfer using integrative vectors might provide a definitive solution and
      support advancement to clinical trials, although studies have not yet been
      satisfactory. To achieve a stable IDUA gene expression in vivo, phiC31 was tested
      in the present study. METHODS: Several plasmid vectors were constructed and IDUA
      /- mice were treated with cyclophosphamide and transfected with these vectors
      hydrodynamically via tail veins. IDUA expression was monitored over time. Treated
      and nontreated mice underwent an open-field test at age 8 months, and IDUA
      activity and glycosaminoglycan (GAG) content of tissues were evaluated. RESULTS:
      High levels of IDUA activity were detected initially (>1000 U/ml), although these
      levels decayed over time. The reinjection of vectors produced a similar profile
      of IDUA decay. Three out of six treated mice had IDUA activity in the livers, and
      also showed lower GAG content, reduced lysosomes and better locomotion. To
      investigate unsustained IDUA production, wild-type mice were submitted to the
      same gene therapy procedure, which generated a similar profile of IDUA decay.
      Anti-IDUA antibody was detected in the sera of these animals. In addition, we
      also found three methylated sites in the cytomegalovirus promoter region.
      CONCLUSIONS: phiC31-mediated gene therapy resulted in an important improvement in
      IDUA-/- mice, including locomotion, although the obstacles that need to be
      overcome to enable long-term gene therapy for MPSI are also noted.

PMID- 25597595
TI  - Novel recombinant chimeric virus-like particle is immunogenic and protective
      against both enterovirus 71 and coxsackievirus A16 in mice.
AB  - Hand-foot-and-mouth disease (HFMD) has been recognized as an important global
      public health issue, which is predominantly caused by enterovirus 71 (EV-A71) and
      coxsackievirus A16 (CVA16). There is no available vaccine against HFMD. An ideal
      HFMD vaccine should be bivalent against both EV-A71 and CVA16. Here, a novel
      strategy to produce bivalent HFMD vaccine based on chimeric EV-A71 virus-like
      particles (ChiEV-A71 VLPs) was proposed and illustrated. The neutralizing epitope
      SP70 within the capsid protein VP1 of EV-A71 was replaced with that of CVA16 in
      ChiEV-A71 VLPs. Structural modeling revealed that the replaced CVA16-SP70 epitope
      is well exposed on the surface of ChiEV-A71 VLPs. These VLPs produced in
      Saccharomyces cerevisiae exhibited similarity in both protein composition and
      morphology as naive EV-A71 VLPs. Immunization with ChiEV-A71 VLPs in mice
      elicited robust Th1/Th2 dependent immune responses against EV-A71 and CVA16.
      Furthermore, passive immunization with anti-ChiEV-A71 VLPs sera conferred full
      protection against lethal challenge of both EV-A71 and CVA16 infection in
      neonatal mice. These results suggested that this chimeric vaccine, ChiEV-A71
      might have the potential to be further developed as a bivalent HFMD vaccine in
      the near future. Such chimeric enterovirus VLPs provide an alternative platform
      for bivalent HFMD vaccine development. 

PMID- 25597597
TI  - Report on the 2013 national cholelithiasis survey in Japan.
AB  - BACKGROUND AND AIMS: The Academic Committee of the Japan Biliary Association
      conducted a national survey of cholelithiasis and analyzed its current management
      centering on epidemiology. METHODS: To allow comparison with previous results, a
      prospective survey was performed on the treatment of cholelithiasis during the
      month of August 2013, using the same questionnaire as that used for the 1997
      Cholelithiasis Survey Project by the Japan Biliary Association. A personal
      questionnaire was sent to 71 institutions, and 612 individual survey sheets were
      collected from 56 institutions as treated during August 2013. RESULTS AND
      CONCLUSIONS: Compared with the results obtained in 1997, the gender ratio was
      reversed in 2013 with male predominance. There were increases in the mean age,
      asymptomatic ratio, use of magnetic resonance cholangiopantreatography for
      diagnosis, and cholesterol stone type was also increased. Laparoscopic
      cholecystectomy was performed for 79.8% of gallbladder stones, and treatment of
      common bile duct stones generally involved endoscopic procedures, among which
      endoscopic sphincterotomy (EST) was performed more often compared with endoscopic
      papillary balloon dilation (EPBD), suggesting that EST is the mainstream
      treatment for common bile duct stones.

PMID- 25597598
TI  - Hyperglycemia decreased medial amygdala projections to medial preoptic area in
      experimental model of Diabetes Mellitus.
AB  - In Wistar rats, reproductive behavior is controlled in a neural circuit of
      ventral forebrain including the medial amygdala (Me), bed nucleus of the stria
      terminalis (BNST) and medial preoptic area (MPOA) via perception of social odors.
      Diabetes Mellitus (DM) is a widespread metabolic disease that affects many organs
      in a variety of levels. DM can cause central neuropathies such as neuronal
      apoptosis, dendritic atrophy, neurochemical alterations and also causes
      reproductive dysfunctions. So we hypothesized damage to the nuclei of this
      circuit can cause reproductive dysfunctions. Therefore in this project we
      assessed diabetic effect on these nuclei. For this purpose neuron tracing
      technique and TUNEL assay were used. We injected HRP in the MPOA and counted
      labeled cells in the Me and BNST to evaluate the reduction of neurons in diabetic
      animals. Also, coronal sections were analyzed with the TMB histochemistry method.
      Animals in this study were adult male Wistar rats (230 +/- 8g) divided to control
      and 10-week streptozotocin-induced diabetic groups. After data analysis by SPSS
      16 software, a significant reduction of HRP-labeled neurons was shown in both Me
      and BNST nuclei in the diabetic group. Moreover, apoptotic cells were
      significantly observed in diabetic animals in contrast to control the group. In
      conclusion, these alterations of the circuit as a result of diabetes might be one
      of the reasons for reproductive dysfunctions. 

PMID- 25597596
TI  - Urethral musculature and innervation in the female rat.
AB  - AIMS: The urethral sphincter and urethral muscle innervation are critically
      involved in maintaining continence, especially in the female. However, the
      urethral muscle type and distribution, as well as the urethral nerves are far
      from being well documented. Our aim was to clearly identify the distribution of
      urethral striated muscle, smooth muscle, and urethral nerves. METHODS: In a
      cohort analysis of 3-month-old female Sprague-Dawley rats, cross and longitudinal
      sections of female rat urethra were extensively investigated using morphological
      techniques. Urethras were harvested to the sections, in order to provide both
      global and detailed visions of the urethra. H&E, Masson's Trichrome, phalloidin
      and immunoflourence stains were used. The cytoarchitecture, nitrergic, and
      cholinergic innervations were mainly investigated. Different layers of the
      segments of urethra were traced to draw curve graphs that represent the thickness
      of each muscle layer of urethral wall. RESULTS: The results showed that the
      primary peak of striated muscle is in the middle urethra. The inner layer close
      to mucosa was found to contain longitudinal smooth muscle. Near the bladder
      orifice, the circular smooth muscle dominates, which becomes thinner distally
      throughout the rest of urethra. In the middle urethra the vast majority of the
      urethral muscle are circularly oriented striated muscle cells. Typical nerve
      endings were present in high power images to show the different characteristic
      features of nerve innervation. CONCLUSIONS: This study has illustrated the
      detailed morphological structure and innervations of the normal female rat
      urethra and can serve as a basis for further study of stress urinary incontinence
      (SUI).

PMID- 25597599
TI  - The neuroprotective effect of a triazine derivative in an Alzheimer's rat model.
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. It is
      characterized by formation of amyloid plaques and neurofibrillary tangles in the
      brain, degeneration of the cholinergic neurons and neural cell death. This study
      was aimed to investigate the effect of a triazine derivative, C16H12Cl2N3S, on
      learning in an Alzheimer's rat model. Animals were divided into seven groups;
      each group contained seven animals. CONTROL GROUP: animals received no surgery
      and treatment; saline group: animals received normal saline after recovery; sham
      group: animals received 10% DMSO after recovery; STZ group (Alzheimer's model):
      animals received streptozotocin (STZ) in four and six days after recovery; T5,
      T10 and T15 groups: animals were treated with triazine derivative, C16H12Cl2N3S,
      at doses of 5, 10 and 15 uM, respectively. All drugs were injected
      intracerebroventricular. The spatial learning and histological assessment were
      performed in all groups. Animals in STZ group had more deficits in spatial
      learning than the control group in Morris water maze. C16H12Cl2N3S improved
      spatial learning significantly compared to STZ group. The CA1 pyramidal layer
      thicknesses in STZ group were reduced significantly compared to control group.
      C16H12Cl2N3S increased the CA1 pyramidal layer thickness in T15 group compared to
      STZ group. Current findings suggest C16H12Cl2N3S may have a protective effect on
      learning deficit and hippocampal structure in AD.

PMID- 25597600
TI  - Trimetazidine prevents oxidative changes induced in a rat model of sporadic type
      of Alzheimer's disease.
AB  - Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease
      (AD) of sporadic origin. The expression of DHCR24 (Seladin-1), marker for
      neuronal oxidative stress and degeneration, has been reported to be altered in
      the brains of AD patients. In the present study, we investigated the effect of
      trimetazidine (TMZ) on the hippocampal oxidative parameters and the expression of
      DHCR24 (Seladin-1) in an animal model of sporadic AD. Male rats were pre-treated
      with TMZ (25 mg/kg) after which injected with intracerebroventricular
      streptozotocin (ICV-STZ)/Saline. Following 2, 7 and 14 days, animals of different
      groups were sacrificed with their brain excised to detect the hippocampal lipid
      peroxidation, superoxide dismutase (SOD), catalase activity, DHCR24 (Seladin-1)
      expression and possible histopathological changes. ICV-STZ administration induced
      significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment
      showed to ameliorate the oxidative stress, which was demonstrated by a
      significant rise in the hippocampal SOD and catalase activity, as well as a
      significant decrease in the malondialdehyde (MDA) level. TMZ administration also
      increased the expression of DHCR24 (Seladin-1) gene in the hippocampus. In
      conclusion, our findings indicated a neuroprotective effect of TMZ possibly
      related to its antioxidant activity resulting in the up-regulation of DHCR24
      (Seladin-1). Such TMZ effects may be beneficial in minimizing oxidative stress in
      sporadic Alzheimer's disease and possible prevention of disease progression.

PMID- 25597601
TI  - Association between adipokine and myeloperoxidase levels in patients with
      coronary artery disease.
AB  - The adipokines, leptin and adiponectin, have a prominent role in the pathogenesis
      of coronary artery disease (CAD). The inflammatory enzyme, myeloperoxidase (MPO)
      also has an important role in the pathogenesis of CAD. Association of the
      adipokines with MPO remains to be resolved in patients with CAD. In this case
      control study, 100 patients with CAD and 100 control subjects were appropriately
      recruited. Angiographic evaluation assigned the presence of CAD. Plasma leptin,
      adiponectin and MPO concentrations were measured using immunoassay methods. Other
      conventional cardiovascular risk factors were also recorded. Leptin and MPO
      concentrations were significantly increased in CAD patients compared to control
      subjects (25.38 +/- 5.91 ng/ml vs. 3.68 +/- 1.95 ng/mL and 52.85 +/- 12.90 ng/mL
      vs.  23.00 +/- 3.60 ng/mL, P=0.001, respectively). In contrast, adiponectin was
      significantly decreased in CAD patients compared to control subjects (5.62 +/-
      1.15 ug/mL vs. 9.25 +/- 1.8, P = 0.001). There was a strong positive association
      between leptin and MPO concentrations only in CAD patients (P = 0.01). In
      contrast, a significant inverse association was found between adiponectin and MPO
      concentrations in CAD patients (P = 0.01). The associations also were significant
      after adjustment for other conventional risk factors (P = 0.001). Considering the
      presence of significant association between leptin and MPO, as well as
      adiponectin and MPO in patients with CAD, it may be inferred that the
      contribution of the adipokines in the pathogenesis of CAD may be, in part,
      through affecting the MPO concentration. 

PMID- 25597602
TI  - Is there a relationship between androgenic alopecia and benign prostatic
      hyperplasia?
AB  - Androgenic alopecia as a physiologic process and benign prostatic hyperplasia
      (BPH) as a pathologic process in the older population are androgen-dependent
      processes influenced by 5-alpha reductase enzyme which converts testosterone to
      dihydrotestosterone. This cross sectional study was done to evaluate the
      relationship between androgenic alopecia and BPH. 150 men older than 50 years
      old, who presented to the free prostate screening clinic, were included. They
      were asked about urinary symptoms. PSA level, prostate volume with sonography and
      alopecia grading using Hamilton-Norwood classification (grade I to VII) were
      evaluated. Analysis was done by SPSS statistical method. 59.6% of men had mild
      alopecia (grade I, II, III), 34.1% had moderate alopecia (grade IV, V) and 6.3%
      had severe alopecia (grade VI, VII).The mean PSA level was 1.37 +/- 1.48 ng/ml.
      The minimum PSA level was 0.1 ng/ml, and the maximum level was 6.8 ng/ml. The
      mean prostate volume was 37.85 +/- 21.85cc. The minimum prostate size was 10 ml,
      and the maximum volume was 173 ml. The mean international prostate symptom score
      (IPSS) was 7.6 +/- 6.11 with the minimum score 0 and the maximum score 27.
      However, no relationship between these parameters and androgenic alopecia was
      detected. This study showed that there is no relationship between androgenic
      alopecia, PSA level, IPSS, and prostate volume. Occurrence of alopecia in younger
      age and a positive family history correlated with a higher grade of alopecia. 

PMID- 25597603
TI  - Interaural difference values of vestibular evoked myogenic.
AB  - Migraine is a neurologic disease, which often is associated with a unilateral
      headache. Vestibular abnormalities are common in migraine. Vestibular evoked
      myogenic potentials (VEMPs) assess otolith function in particular functional
      integrity of the saccule and the inferior vestibular nerve. We used VEMP to
      evaluate if the migraine headache can affect VEMP asymmetry parameters. A total
      of 25 patients with migraine (22 females and 3 males) who were diagnosed
      according to the criteria of IHS-1988 were enrolled in this cross-sectional
      study. Control group consisted of 26 healthy participants (18 female and 8 male),
      without neurotological symptoms and history of migraine. The short tone burst (95
      dB nHL, 500 Hz) was presented to ears. VEMP was recorded with surface
      electromyography over the contracted ipsilateral sternocleidomastoid (SCM)
      muscle. Although current results showed that the amplitude ratio is greater in
      migraine patients than normal group, there was no statistical difference between
      two groups in mean asymmetry parameters of VEMP. Asymmetry measurements in
      vestibular evoked myogenic potentials probably are not indicators of unilateral
      deficient in saccular pathways of migraine patients. 

PMID- 25597605
TI  - Is the evaluation of Entamoeba histolytica infection in HIV-positive patients of
      any clinical significance?
AB  - Amoebiasis caused by Entamoeba histolytica (E. histolytica) is one of the most
      problematic parasitic infections worldwide. Data regarding the effect of HIV
      induced immunodeficiency on the status of E. histolytica infection are sparse in
      Iran. This study aimed to assess the seroprevalence of anti-E. histolytica IgG
      among Iranian HIV patients. Further, it determined whether the advancement of
      immunodeficiency accompanies an increased risk of amoebiasis. A total of 91 HIV
      infected patients and 91 controls were enrolled in this case-control study.
      Controls were matched to cases with respect to age, gender, and where possible
      socioeconomic status. Patients with a history of treatment for intestinal
      parasitism within last two weeks were not included in the study. Blood samples
      were obtained from all participants. Serum IgG against E. histolytica measured
      using a commercial enzyme-linked immunosorbent assay (ELISA). The mean serum anti
      E. histolytica IgG was significantly higher in HIV patients than controls (9.34
      +/- 4.18 vs. 2.07 +/- 0.60, P<0.001). HIV-infected patients showed a
      significantly higher positive serology for E. histolytica IgG comparing healthy
      controls (30.8% vs. 0% P<0.001). There was no statistical difference in the
      serology of E. histolytica among AIDS stage and non-AIDS HIV patients. This study
      demonstrated that HIV is significantly associated with higher prevalence of E.
      histolytica infection. Early evaluation and treatment of E. histolytica in this
      population is recommended to prevent and control this infection. 

PMID- 25597604
TI  - The effects of secondhand smoke exposure on infant growth: a prospective cohort
      study.
AB  - Mother's and infant exposure to cigarette smoke is one of the most important
      public health problems. There is no study in Iran evaluating the impact of
      cigarette smoke on infant growth and development. The purpose of this study was
      to determine the effects of cigarette. This prospective cohort study was
      conducted on 51 cigarette smoke-exposed infants (exposed group) and 51 non
      exposed infants (non-exposed group). They were evaluated for weight, height and
      head circumference three times; five to seven days, two months and four months
      after birth. Urine samples were also collected in each turn. Exposure to
      secondhand smoke was assessed through questionnaires and urinary cotinine levels.
      The analysis was performed using an independent t-test, Mann-Whitney U test, chi
      square and Fisher's exact and Kappa tests. Mean urinary cotinine level in the
      exposed group was 38.57+/-2.85 ng/mg creatinine at baseline, 86.95+/-1.16 at two
      months and 63.32+/-2.08 at four months of age. These indicated a gradual
      reduction of exposure from two to four months. The weight and height of the
      exposed group were significantly lower than the non-exposed group (P< 0.001) at
      two and four months after birth. The results of the present study showed that the
      exposure to secondhand smoke during infancy may lead to weight and height growth
      reduction in the first four months of life. 

PMID- 25597606
TI  - Acute Respiratory Distress Syndrome diagnosis after coronary artery bypass:
      comparison between diagnostic criteria and clinical picture.
AB  - Acute Respiratory Distress Syndrome (ARDS) is a potential complication of cardiac
      surgery, given that patients undergoing CABG frequently have hypoxemia and
      pulmonary dysfunction during initial hours after surgery. Thus, ARDS criteria in
      these patients are more likely to be positive while these criteria may not match
      the patient's clinical picture. We aimed to investigate frequency of rapid onset
      hypoxemia in Pressure of Arterial Oxygen to Fractional Inspired Oxygen
      Concentration (PaO2/FiO2) less than 200 and diffuse pulmonary infiltrates as two
      diagnostic criteria forwards and compared these criteria with the clinical
      picture of the patients after Coronary Artery Bypass Graft (CABG) in this study.
      The study was prospective case series which carried out in about six months. All
      patients admitted to intensive care unit of Tehran Heart Center, who had
      undergone CABG on cardiopulmonary pump (CPB) recruited in the study. After
      considering inclusion criteria, age, sex, duration of intubation, arterial blood
      gas and chest radiography, on 24 hours and 48 hours after admission to the ICU
      were recorded. Then, patients with rapid onset of hypoxemia (PaO2/FiO2<=200mmHg)
      and diffuse pulmonary infiltrates and without sign or symptoms of obvious heart
      failure (probable positive ARDS cases) criteria were recorded and comparison
      between these probable positive cases with clinician's clinical diagnosis
      (blinded to the study) was performed. In this study, a total of 300 patients
      after on-pump coronary artery bypass surgery were included. Postoperatively, 2
      (0.66 %) in the 24 hours and 4 (1.33%) patients in 48 hours after surgery were
      positive for the two ARDS criteria according to the checklists, but; nobody had
      saved persistently ARDS criteria persistently during 48 hours after surgery. At
      the same time, clinician did not report any case of ARDS among 300 patients. In
      this study patients with ARDS criteria had no significant differences in age
      (P.value=0.937) and sex (P.value=0.533). Duration of intubation in patients with
      ARDS (14.26 +/- 4.25 hours) in the first 48 hours was higher but not
      statistically different from the group without ARDS (11.60 +/- 5.45 hours)
      (P.value=0.236). ARDS diagnosis based on rapid onset of hypoxemia (PaO2/FiO2<=200
      mmHg) and diffuse pulmonary infiltrates and without signs or symptoms of obvious
      heart failure criteria in patients undergoing CABG could lead to overdiagnosis or
      misdiagnosis in less than 24 hours follow up. We recommend following patients for
      more than 24 hours and revise the current ARDS criteria for CABG patients. 

PMID- 25597607
TI  - The effect of posterior pericardiotomy on pericardial effusion and atrial
      fibrillation after off-pump coronary artery bypass graft.
AB  - The most common type of arrhythmia following coronary artery bypass graft (CABG)
      is atrial fibrillation (AF) with an incidence rate of 20-30%. Pericardial
      effusion is one of the etiologic factors of atrial fibrillation occurring after
      CABG. Posterior pericardiotomy (PP) causes the drainage of blood and fluids from
      the pericardial space into the pleural space leading to a decreased pericardial
      effusion. Most of the studies dealing with the occurrence of AF in the surgical
      operation of CABG have focused on patients undergoing on-pump CABG. The purpose
      of the present study was to determine the effect of posterior pericardiotomy on
      pericardial effusion and atrial fibrillation following the off-pump CABG. This
      study was a clinical trial conducted on 207 patients. The patients were randomly
      assigned to groups A, and B. Posterior pericardiotomy was performed on the
      patients in Group A. This was not done on patients in Group B. Following general
      anesthesia and median sternotomy, the left internal mammary artery (LIMA) and
      saphenous vein were harvested simultaneously. Following the injection of heparin,
      distal and proximal anastomosis was performed and at the end of surgery, a
      longitudinal incision with a length of 4 cm was performed parallel and posterior
      to the left phrenic nerve from the left vein to diaphragm for patients in the
      pericardiotomy group. 105 patients in the pericardiotomy group and 102 patients
      in the control group were examined regarding demographic variables, AF incidence,
      and pericardial effusion. There was no statistically significant correlation
      between two groups. There was no statistically significant difference between the
      two groups regarding the rate of AF incidence (P=0.719) and the rate of
      pericardial effusion (P=1). Posterior pericardiotomy has no effect on
      postoperative AF incidence and pericardial effusion in patients undergoing the
      off-pump CABG. 

PMID- 25597609
TI  - Eosinophilic granuloma of the skull base: patient with unique clinical moreover,
      radiographic presentation.
AB  - This case report presents an eight-year-old girl having periauricular swelling
      and severe pain during mouth opening on the right-side temporomandibular joint
      (TMJ). CBCT showed extensive destruction of the base of the skull and the roof of
      the glenoid fossa on the right side. The findings based on CT and MRI images with
      and without contrast are discussed herein. This report highlights a skull base
      eosinophilic granuloma that mimics TMJ disorder and the importance of proper
      evaluation of CBCT images to make an early diagnosis. 

PMID- 25597608
TI  - Sociocultural factors associated with breast self-examination among Iranian
      women.
AB  - Of the ways to fight breast cancer and reduce deaths hazard due to early
      detection is one of early detection programs in women's breast self- examination.
      Examining breast by oneself increase individuals knowledge of her breast health
      that helps in detecting breast cancer early. Different cultural, social, family
      and individual factors play roles in women's behavior about breast self-
      examination applying PEN-3 model in this study is to analyze factors influencing
      on breast self-examination. The research is a descriptive- analytical, cross
      sectional type. Research community consists of women at fertility age of 20-49 in
      sari. Sample volume is 415 individuals and sampling method is cluster method. In
      this study, a 50-item questionnaire based on PEN-3 was used. Questions were
      answered by Likert scoring method. Questionnaire was gathered by personal
      presence of questioners. Data was analyzed via descriptive statistics and
      logistic regression methods. Based on the study findings, the most significant
      positive behaviors related to perceptual factors included effectiveness of
      disease background in family and relatives (73%), believing in breast self-
      examination for pursuing health (93%) and the most important negative behaviors
      were shyness and modesty (83.9%) and increased worry (78.9%). The most remarkable
      positive behaviors regarding enabling factors covered the skill to do breast
      examination oneself (35.2%), the availability of health and therapeutic centers
      (80.7%) and the most significant negative behavior was being busy and lack of
      time (85.3%). The most important positive behavior about nurturing factors
      included family consent (68.9%) and the most significant negative one was the
      inappropriate treatment of health and therapeutic personnel (61.8%). In this
      study, there is a meaningful difference between employment ages, education with
      PEN-3 model constituents. Since behaviors due to enabling and nurturing
      perceptual factors have been important in doing or not doing breast self-
      examination; thus its worth to take measures to plan some educational and
      administrative intervention programs about women breast cancer early detection
      through sufficient knowledge of influential sociocultural factors.

PMID- 25597610
TI  - Concomitant splenic and hepatic hydatidosis: report of two cases and review of
      the literature.
AB  - Hydatid disease has a worldwide spreading. The most common site of the disease is
      the liver, lungs, kidney, bones, and brain. Splenic hydatid disease has been
      reported to constitute 2% to 6% of patients with abdominal hydatid disease.
      Because of the rarity of splenic hydatid disease, the probable concomitance of
      the liver and splenic hydatid cysts should be taken into consideration by
      clinicians, especially in nonendemic areas. In this report, we present two
      patients with concomitant splenic and liver hydatid cysts that underwent
      splenectomy and cystostomy-capitonage. 

PMID- 25597611
TI  - The anti-osteoporosis and antioxidant activities of chemical constituents from
      Chrysanthemum indicum flowers.
AB  - Two new compounds, chrysinoneside A (1) and (-)-trans-chrysanthenol-6-O-beta-D
      glucopyranoside (2), along with 17 known compounds (3-19) were isolated from
      Chrysanthemum indicum flowers. The total phenolic and flavonoid contents of
      various fractions were determined. The EtOAC fraction had the highest total
      phenolic content (525.84 +/- 23.51 mg GAE/g DR) and the total flavonoid content
      (63.49 +/- 3.32 mg QE/g DR). The EtOAc and water fractions showed the greatest
      peroxyl radical-scavenging capacity and the ability to reduce Cu(I) ions, with
      ORAC and CUPRAC values ranging from 24.00 +/- 0.44 to 28.06 +/- 1.35 and 16.90 +/
      0.51 to 49.77 +/- 0.97 MUM, respectively. Compounds 5-11, 18, and 19 displayed
      strong effects in both peroxyl radical-scavenging and reducing capacity assays at
      a concentration of 10 MUM. The anti-osteoporosis activity of these compounds was
      also evaluated. Compounds 10, 13, and 19 exhibited the most potent tartrate
      resistant acid phosphatase activity in receptor activator of nuclear factor
      kappaB ligand-induced osteoclastic RAW 264.7 cells with values of 105.95 +/-
      1.18, 110.32 +/- 3.95, and 112.58 +/- 6.42%, respectively.

PMID- 25597612
TI  - Expression profile analysis of microRNAs in prostate cancer by next-generation
      sequencing.
AB  - BACKGROUND: Prostate cancer (PCa) is the second leading cause of tumor mortality
      among males in western societies. In China, the diagnostic and fatality rate of
      PCa is increasing yearly. METHODS: To characterize underlying molecular
      mechanisms, the microRNA (miRNA) profile of high-grade PCa, low-grade PCa, and
      benign prostate hyperplasia (BPH) were compared using high-throughput Illumina
      sequencing and quantitative real-time PCR (qRT-PCR) methods. Moreover, a variety
      of biological information softwares and databases were applied to predict the
      target genes of miRNA, molecular functions, and signal pathways. RESULTS:
      Eighteen miRNAs were differentially expressed (fold change >= 2, P < 0.05), of
      which thirteen were upregulated and five were downregulated by sequencing. This
      was confirmed by qRT-PCR in more clinical tissue samples. In the tumors, miRNAs
      (miR-125b-5p, miR-126-5p, miR-151a-5p, miR-221-3p, and miR-222-3p) were
      significantly upregulated with downregulation of miR-486-5p. In addition, 13
      novel miRNAs were identified from three prostate tissue libraries, with 12 of
      them assayed in 21 human normal tissues by qRT-PCR. Multiple databases indicated
      target genes for these differentially expressed miRNAs. Function annotation of
      target genes indicated that most of them tend to target genes involved in signal
      transduction and cell communication, especially cancer-related PI3K-Akt and p53
      signaling pathway. CONCLUSIONS: The small RNA transcriptomes obtained in this
      study uncovers six differentially expressed miRNAs and 12 novel miRNAs, and
      provides a better understanding of the expression and function of miRNAs in the
      development of PCa and reveals several miRNAs in PCa that may have biomarker and
      therapeutic potentials.

PMID- 25597613
TI  - Young adults' reactions to infant crying.
AB  - AIM: To determine whether young childless adults show negative emotions and
      cognitive disturbances when listening to infant crying, compared to other
      disturbing noises, and whether negative emotions and cognitive disturbances are
      associated. METHODS: We tested the cognitive performances and emotional reactions
      of 120 childless participants on a working memory task while being subjected to
      different disturbing noises including infant crying. RESULTS: Participants had
      the least correct trials on the working memory task, and showed the most negative
      emotions, when hearing infant crying as compared to the other noises.
      Participants also showed less positive emotions when hearing infant crying as
      compared to working in silence. Overall, negative emotions were associated with
      less correct trials on the working memory task, except in the infant crying
      condition. Furthermore, cognitive performance and emotional reactions to infant
      crying were unrelated to personality characteristics. CONCLUSION: Negative
      emotions and cognitive disturbances may be general adult responses to infant
      crying that are not limited to parents. These results suggest a broadly present
      human emotional and cognitive response to infant crying, that may underlie a
      general predisposition to care for infants in distress.

PMID- 25597615
TI  - Diagnostic value of serum complement C3 and C4 levels in Chinese patients with
      systemic lupus erythematosus.
AB  - In 2009, hypocomplementemia involving C3, C4, and total hemolytic complement
      (CH50) was proposed as an immunologic criterion to enhance the sensitivity of
      systemic lupus erythematosus (SLE) classification criteria. This study evaluated
      the diagnostic value of low serum complement C3 and C4 levels in Chinese patients
      with SLE. In total, 2452 patients were enrolled in this study (158 with SLE and
      2294 with other diseases). Receiver operating characteristic analysis showed that
      the optimal C3 and C4 cut-off levels for a diagnosis of SLE were 0.785 g/L
      (sensitivity, 77.9%; specificity, 81.5%) and 0.145 g/L (sensitivity, 80.1%;
      specificity, 83.2%), respectively. The prevalence of a low C3 or C4 level alone
      was similar between patients with SLE and those with other diseases, while the
      prevalence of simultaneously low C3 and C4 levels was higher in patients with SLE
      (73.42%). Antinuclear antibody had a high sensitivity (96.64%) and low negative
      likelihood ratio (0.04). Hypocomplementemia with positive antinuclear antibody
      had a high positive likelihood ratio. Inclusion of hypocomplementemia as a
      classification criterion for SLE resulted in a 16.18% increase in the number of
      patients assigned to the SLE group (from 136 to 158 patients). Hypocomplementemia
      was highly prevalent in patients with hematological disease (41.94%). These
      results suggest that hypocomplementemia has important diagnostic value for SLE by
      improving the sensitivity of the diagnosis of SLE. C3 and C4 should be tested
      simultaneously because a low C3 or C4 level alone is not a suitable immunological
      criterion.

PMID- 25597617
TI  - Prospective cardiac MRI for the analysis of biventricular function in children
      undergoing cancer treatments.
AB  - BACKGROUND: Cardiotoxicity is one of the most serious long-term complications in
      childhood cancer survivors. Measurement of the left ventricular ejection and
      shortening fraction remains the most common screening tool for cardiac systolic
      dysfunction. However, M-mode echocardiography can be viewed as a crude approach
      as refined strategies are now available. The aim of this prospective study was to
      determine the role of cardiac MRI in the detection of subclinical left or right
      ventricular dysfunction as well as the prevalence of myocardial scaring in
      patients undergoing cancer treatments. PROCEDURE: Eighty-one children were
      enrolled in a pre-chemotherapy and then in a yearly protocol including a: (i)
      clinical evaluation; (ii) laboratory evaluation; (iii) electrocardiogram; (iv)
      echocardiogram; and (v) a cardiac magnetic resonance imaging (cMRI). RESULTS:
      Early left ventricular systolic dysfunction was only detected in two patients.
      The entire cohort presented a significant increase of the left atrial volume as
      measured by cMRI. This finding correlated with the total cumulative dose of
      anthracyclines (r = 0.34; P < 0.05) and the mean left ventricular radiation dose
      (r = 0.86; P < 0.05). We also observed a mild increase of myocardial scaring,
      similarly correlated to the radiation dose (r = 0.85; P < 0.05). CONCLUSIONS:
      Screening tools for late-onset cardiomyopathy secondary to cancer treatment are
      lacking. Our findings support the use of cMRI for the evaluation of the left
      atrial volume, as an early marker of diastolic dysfunction, and myocardial
      delayed enhancement, as a marker of myocardial fibrosis and scaring. Longer
      follow-up and larger studies are still needed to better define the role of cMRI
      in the evaluation of childhood cancer survivors.

PMID- 25597616
TI  - Decrease of LL-37 in systemic sclerosis: a new marker for interstitial lung
      disease?
AB  - Interstitial lung disease (ILD) is the leading cause of systemic sclerosis (SSc)
      related morbidity and mortality. LL-37 peptide is the only cathelicidin of the
      human antimicrobial peptide family with antimicrobial effects and
      immunomodulatory activity. LL-37 has anti-fibrotic effects and anti-apoptotic
      effects on SSc dermal fibroblasts. The aim of the study was to investigate the
      circulating levels of LL-37 in SSc patients and its association with clinical,
      laboratory, and instrumental parameters. Fifty-eight SSc patients (30 with and 28
      without pulmonary involvement) and 28 healthy controls were enrolled in the
      study. Pulmonary involvement was defined when ILD was found at HRCT (ground
      glass, reticular, and honeycombing pattern). Circulating LL-37 levels were
      measured with ELISA test. In SSc patients with ILD serum, LL-37 concentrations
      were remarkably lower (1.36 mg/ml) than those in SSc patients without ILD (4.62
      ng/ml, p = 0.035) and controls (5.53 ng/ml, p = 0.009). In SSc patients without
      ILD, serum LL-37 levels were not different from controls (p = 0.812). No
      significant association or correlation was found between LL-37 levels and any
      other clinical, serological, or instrumental features. Serum LL-37 levels are
      significantly lower in patients with SSc ILD. Our results may suggest that lower
      LL-37 levels may be associated with the development of ILD. Whether circulating
      levels of LL-37 might be used as an indirect marker of ILD remains to be
      determined in larger SSc cohorts.

PMID- 25597618
TI  - Application of freeze-drying technology in manufacturing orally disintegrating
      films.
AB  - Freeze drying technology has not been maximized and reported in manufacturing
      orally disintegrating films. The aim of this study was to explore the freeze
      drying technology in the formulation of sildenafil orally disintegrating films
      and compare the physical properties with heat-dried orally disintegrating film.
      Central composite design was used to investigate the effects of three factors,
      namely concentration of carbopol, wheat starch and polyethylene glycol 400 on the
      tensile strength and disintegration time of the film. Heat-dried films had higher
      tensile strength than films prepared using freeze-dried method. For folding
      endurance, freeze-dried films showed improved endurance than heat-dried films.
      Moreover, films prepared using freeze-dried methods were thicker and had faster
      disintegration time. Formulations with higher amount of carbopol and starch
      showed higher tensile strength and thickness whereas formulations with higher PEG
      400 content showed better flexibility. Scanning electron microscopy showed that
      the freeze-dried films had more porous structure compared to the heat-dried film
      as a result of the release of water molecule from the frozen structure when it
      was subjected to freeze drying process. The sildenafil film was palatable. The
      dissolution profiles of freeze-dried and heat-dried films were similar to
      Viagra(r) with f2 of 51.04 and 65.98, respectively. 

PMID- 25597614
TI  - Resistance strength training exercise in children with spinal muscular atrophy.
AB  - INTRODUCTION: Preliminary evidence in adults with spinal muscular atrophy (SMA)
      and in SMA animal models suggests exercise has potential benefits in improving or
      stabilizing muscle strength and motor function. METHODS: We evaluated
      feasibility, safety, and effects on strength and motor function of a home-based,
      supervised progressive resistance strength training exercise program in children
      with SMA types II and III. Up to 14 bilateral proximal muscles were exercised 3
      times weekly for 12 weeks. RESULTS: Nine children with SMA, aged 10.4 +/- 3.8
      years, completed the resistance training exercise program. Ninety percent of
      visits occurred per protocol. Training sessions were pain-free (99.8%), and no
      study-related adverse events occurred. Trends in improved strength and motor
      function were observed. CONCLUSIONS: A 12-week supervised, home-based, 3-day/week
      progressive resistance training exercise program is feasible, safe, and well
      tolerated in children with SMA. These findings can inform future studies of
      exercise in SMA.

PMID- 25597619
TI  - Preparation of valnemulin hydrogen fumarate and its enhanced stability compared
      with valnemulin hydrochloride.
AB  - CONTEXT: It is necessary to develop a new salt of valnemulin to replace the
      veterinary antibiotic, e.g. valnemulin hydrochloride, in order to overcome its
      instability during storage and preparation. OBJECTIVE: The objective of this
      study was to prepare a novel organic acid salt, valnemulin hydrogen fumarate, and
      to investigate its stability compared with valnemulin hydrochloride. MATERIALS
      AND METHODS: The crystal of valnemulin hydrogen fumarate was prepared by modified
      crystallization method; the enhanced stabilities of valnemulin hydrogen fumarate
      were conducted under irradiation and humid conditions, and the experimental
      results were simulated at AM1 level of calculations. RESULTS: Valnemulin hydrogen
      fumarate was more stable than valnemulin hydrochloride. After irradiation for 180
      days, the content of valnemulin hydrogen fumarate decreased slightly 2.7%,
      whereas the content of valnemulin hydrochloride had an obvious decrease of 32.8%.
      Meanwhile, valnemulin hydrogen fumarate showed better anti-RH (relative humidity)
      ability than valnemulin hydrochloride. Under conditions of 65% and 85% RH, the
      absorption values of valnemulin hydrogen fumarate towards water were 0.75% and
      1.20% at 48 h, whereas those of valnemulin hydrochloride were 4.50% and 9.71%,
      respectively. CONCLUSION: The enhanced stability of valnemulin hydrogen fumarate
      could be attributed to its good crystallinity in comparison with the amorphous
      valnemulin hydrochloride.

PMID- 25597620
TI  - Development and validation of a question prompt list for parents of children with
      attention-deficit/hyperactivity disorder: a Delphi study.
AB  - OBJECTIVES: Question prompt lists (QPLs) are structured lists of disease and
      treatment-specific questions intended to encourage patient question-asking during
      consultations with clinicians. The aim of this study was to develop a QPL
      intended for use by parents of children affected by attention
      deficit/hyperactivity disorder (ADHD). METHODS: The QPL content (111 questions)
      was derived through thematic analysis of existing ADHD- and QPL-related
      resources. A modified Delphi method, involving a three-round web-based survey,
      was used to reach consensus about the QPL content. Thirty-six experts were
      recruited into either a professional [paediatricians, child and adolescent
      psychiatrists, psychologists, researchers (n =28)] or non-professional panel
      [parents of children diagnosed with ADHD, ADHD consumer advocates (n = 8)]. Panel
      members were asked to rate the importance of the QPL content using a five-point
      scale ranging from 'Essential' to 'Should not be included'. RESULTS: A total of
      122 questions, including 11 new questions suggested by panellists, were rated by
      both panels. Of these, 88 (72%) were accepted for inclusion in the QPL. Of the
      accepted questions, 39 were re-rated during two follow-up survey rounds and 29
      (74%) were subsequently accepted for inclusion. The questions covered key topics
      including diagnosis, understanding ADHD, treatment, health-care team, monitoring
      ADHD, managing ADHD, future expectations and support and information.
      CONCLUSIONS: To our knowledge, this is the first ADHD-specific QPL to be
      developed and the first use of the Delphi method to validate the content of any
      QPL. It is anticipated that the QPL will assist parents in obtaining relevant,
      reliable information and empowering their treatment decisions by enhancing the
      potential for shared decision making with clinicians.

PMID- 25597621
TI  - A model of face selection in viewing video stories.
AB  - When typical adults watch TV programs, they show surprisingly stereo-typed gaze
      behaviours, as indicated by the almost simultaneous shifts of their gazes from
      one face to another. However, a standard saliency model based on low-level
      physical features alone failed to explain such typical gaze behaviours. To find
      rules that explain the typical gaze behaviours, we examined temporo-spatial gaze
      patterns in adults while they viewed video clips with human characters that were
      played with or without sound, and in the forward or reverse direction. We here
      show the following: 1) the "peak" face scanpath, which followed the face that
      attracted the largest number of views but ignored other objects in the scene,
      still retained the key features of actual scanpaths, 2) gaze behaviours remained
      unchanged whether the sound was provided or not, 3) the gaze behaviours were
      sensitive to time reversal, and 4) nearly 60% of the variance of gaze behaviours
      was explained by the face saliency that was defined as a function of its size,
      novelty, head movements, and mouth movements. These results suggest that humans
      share a face-oriented network that integrates several visual features of multiple
      faces, and directs our eyes to the most salient face at each moment. 

PMID- 25597622
TI  - Exploring the transition experiences of students entering into preregistration
      nursing degree programs with previous professional nursing qualifications: an
      integrative review.
AB  - AIMS AND OBJECTIVES: This paper aims to investigate the transition experiences of
      students with previous nursing qualifications (nondegree qualifications) entering
      a nursing degree program. BACKGROUND: Nurses with professional nursing
      qualifications (nondegree) are an important pool of professionals to draw on to
      help address nursing shortages through providing alternative pathways to becoming
      registered nurses. However, research suggests this cohort need higher levels of
      support and intervention to be successful. DESIGN: An integrative review was
      conducted, guided by Whittemore and Knafl's framework. A comprehensive search was
      conducted and 14 studies were included in the review. METHODS: A five-stage
      approach was used to conduct the review: problem identification, literature
      search, data evaluation, data analysis and presentation of results. Constant
      comparative analysis was used to identify commonalities, differences and themes
      in the relevant literature. RESULTS: Themes emerged that suggested students
      struggled with academic and institutional challenges, becoming learners, managing
      conflicting demands of outside life, developing a student identity and
      experienced threat to their sense of professional identity. Additionally, the
      cohort did not view themselves as 'the same' as traditional students. Holland's
      framework provides a useful framework from which to conceptualise these students'
      experiences. CONCLUSION: There are challenges for this cohort of students as they
      transition into degree level study. Supportive activities that extend and further
      develop students' personality orientations may be a useful starting point in
      addressing some of the challenges and providing a more positive transition to
      university. RELEVANCE TO CLINICAL PRACTICE: The demand for health care is growing
      and there remains a shortfall of registered nurses. Nurses with professional
      qualifications (nondegree) are an important pool of professionals from which to
      increase registered nurse numbers and address workforce sustainability issues.

PMID- 25597623
TI  - Central obesity is predictive of persistent storage lower urinary tract symptoms
      (LUTS) after surgery for benign prostatic enlargement: results of a multicentre
      prospective study.
AB  - OBJECTIVE: To evaluate the impact of components of metabolic syndrome (MetS) on
      urinary outcomes after surgery for severe lower urinary tract symptoms (LUTS) due
      to benign prostatic enlargement (BPE), as central obesity can be associated with
      the development of BPE and with the worsening of LUTS. PATIENTS AND METHODS: A
      multicentre prospective study was conducted including 378 consecutive men
      surgically treated for large BPE with simple open prostatectomy (OP) or
      transurethral resection of the prostate (TURP), between January 2012 and October
      2013. LUTS were measured by the International Prostate Symptom Score (IPSS),
      immediately before surgery and at 6-12 months postoperatively. MetS was defined
      according the USA National Cholesterol Education Program-Adult Treatment Panel
      III. RESULTS: The improvement of total and storage IPSS postoperatively was
      related to diastolic blood pressure and waist circumference (WC). A WC of >102 cm
      was associated with a higher risk of an incomplete recovery of both total IPSS
      (odds ratio [OR] 0.343, P = 0.001) and storage IPSS (OR 0.208, P < 0.001), as
      compared with a WC of <102 cm. The main limitations were: (i) population selected
      from a tertiary centre, (ii) Use exclusively of IPSS questionnaire, and (iii) No
      inclusion of further data. CONCLUSIONS: Increased WC is associated with
      persistent postoperative urinary symptoms after surgical treatment of BPE. Obese
      men have a higher risk of persistent storage LUTS after TURP or OP.

PMID- 25597624
TI  - Ion selectivity in the selectivity filters of acid-sensing ion channels.
AB  - Sodium-selective acid sensing ion channels (ASICs), which belong to the
      epithelial sodium channel (ENaC) superfamily, are key players in many
      physiological processes (e.g. nociception, mechanosensation, cognition, and
      memory) and are potential therapeutic targets. Central to the ASIC's function is
      its ability to discriminate Na(+) among cations, which is largely determined by
      its selectivity filter, the narrowest part of an open pore. However, it is
      unclear how the ASIC discriminates Na(+) from rival cations such as K(+) and
      Ca(2+) and why its Na(+)/K(+) selectivity is an order of magnitude lower than
      that of the ENaC. Here, we show that a well-tuned balance between electrostatic
      and solvation effects controls ion selectivity in the ASIC1a SF. The large, water
      filled ASIC1a pore is selective for Na(+) over K(+) because its backbone ligands
      form more hydrogen-bond contacts and stronger electrostatic interactions with
      hydrated Na(+) compared to hydrated K(+). It is selective for Na(+) over divalent
      Ca(2+) due to its relatively high-dielectric environment, which favors solvated
      rather than filter-bound Ca(2+). However, higher Na(+)-selectivity could be
      achieved in a narrow, rigid pore lined by three weak metal-ligating groups, as in
      the case of ENaC, which provides optimal fit and interactions for Na(+) but not
      for non-native ions. 

PMID- 25597625
TI  - Atomistic description of thiostannate-capped CdSe nanocrystals: retention of four
      coordinate SnS4 motif and preservation of Cd-rich stoichiometry.
AB  - Colloidal semiconductor nanocrystals (NCs) are widely studied as building blocks
      for novel solid-state materials. Inorganic surface functionalization, used to
      displace native organic capping ligands from NC surfaces, has been a major
      enabler of electronic solid-state devices based on colloidal NCs. At the same
      time, very little is known about the atomistic details of the organic-to
      inorganic ligand exchange and binding motifs at the NC surface, severely limiting
      further progress in designing all-inorganic NCs and NC solids. Taking
      thiostannates (K4SnS4, K4Sn2S6, K6Sn2S7) as typical examples of
      chalcogenidometallate ligands and oleate-capped CdSe NCs as a model NC system, in
      this study we address these questions through the combined application of
      solution (1)H NMR spectroscopy, solution and solid-state (119)Sn NMR
      spectroscopy, far-infrared and X-ray absorption spectroscopies, elemental
      analysis, and by DFT modeling. We show that through the X-type oleate-to
      thiostannate ligand exchange, CdSe NCs retain their Cd-rich stoichiometry, with a
      stoichiometric CdSe core and surface Cd adatoms serving as binding sites for
      terminal S atoms of the thiostannates ligands, leading to all-inorganic
      (CdSe)core[Cdm(Sn2S7)yK(6y-2m)]shell (taking Sn2S7(6-) ligand as an example).
      Thiostannates SnS4(4-) and Sn2S7(6-) retain (distorted) tetrahedral SnS4 geometry
      upon binding to NC surface. At the same time, experiments and simulations point
      to lower stability of Sn2S6(4-) (and SnS3(2-)) in most solvents and its lower
      adaptability to the NC surface caused by rigid Sn2S2 rings. 

PMID- 25597626
TI  - Relationships between volatile compounds and sensory characteristics in virgin
      olive oil by analytical and chemometric approaches.
AB  - BACKGROUND: The volatile fraction of virgin olive oil is characterised by low
      molecular weight compounds that vaporise at room temperature. In order to obtain
      an aroma profile similar to natural olfactory perception, the composition of the
      volatile compounds was determined by applying dynamic headspace gas
      chromatography, performed at room temperature, with a cryogenic trap directly
      connected to a gas chromatograph-mass spectrometer system. Samples were also
      evaluated according to European Union and International Olive Council official
      methods for sensory evaluation. In this paper, the composition of the volatile
      fraction of 25 extra virgin olive oils from different regions of Italy was
      analysed and some preliminary considerations on relationships between chemical
      composition of volatile fraction and sensory characteristics are reported.
      RESULTS: Forty-two compounds were identified by means of the particular
      analytical technique used. All the analysed samples, classified as extra virgin
      by the panel test, never present peaks whose magnitude is important enough in
      defected oils. The study was focused on the evaluation of volatile compounds
      responsible for the positive impact on olive odour properties ('green-fruity' and
      'sweet') and olfactory perception. CONCLUSION: Chemometric evaluation of data,
      obtained through headspace analysis and the panel test evaluation, showed a
      correlation between chemical compounds and sensory properties. On the basis of
      the results, the positive attributes of virgin olive oil are divided into two
      separated groups: sweet types or green types. Sixteen volatile compounds with
      known positive impact on odour properties were extracted and identified. In
      particular, eight compounds seem correlated with sweet properties whereas the
      green sensation appears to be correlated with eight other different substances.
      The content of the compounds at six carbon atoms proves to be very important in
      defining positive attributes of extra virgin olive oils and sensory evaluation.

PMID- 25597627
TI  - Remodelling of spared proprioceptive circuit involving a small number of neurons
      supports functional recovery.
AB  - Studies show that limited functional recovery can be achieved by plasticity and
      adaptation of the remaining circuitry in partial injuries in the central nervous
      system, although the new circuits that arise in these contexts have not been
      clearly identified or characterized. We show here that synaptic contacts from
      dorsal root ganglions to a small number of dorsal column neurons, a caudal
      extension of nucleus gracilis, whose connections to the thalamus are spared in a
      precise cervical level 1 lesion, underwent remodeling over time. These
      connections support proprioceptive functional recovery in a conditioning lesion
      paradigm, as silencing or eliminating the remodelled circuit completely abolishes
      the recovered proprioceptive function of the hindlimb. Furthermore, we show that
      blocking repulsive Wnt signalling increases axon plasticity and synaptic
      connections that drive greater functional recovery. 

PMID- 25597628
TI  - Vacuum-assisted closure for skin necrosis after revision total knee arthroplasty.
AB  - Although skin necrosis following total knee arthroplasty or revision total knee
      arthroplasty is rare, it may cause severe complications. Skin changes begin with
      superficial infections and may result in removal of the prosthesis. Treatment of
      skin necrosis is an important factor, which determines the prognosis of the
      prosthesis. Several techniques have been defined for sufficient closure. In this
      article, we present the case of a patient who was treated for skin necrosis that
      developed after knee revision arthroplasty, using serial debridement, convergence
      sutures and an intermittent vacuum-assisted closure device (KCI Inc., San
      Antonio, TX). 

PMID- 25597629
TI  - Surgical robots for SPL and NOTES: a review.
AB  - INTRODUCTION: Single port laparoscopy (SPL) and natural orifice transluminal
      endoscopic surgery (NOTES) are next-generation minimally invasive surgery (MIS)
      procedures which could further reduce patient trauma. Robotic assistance shows
      great potential in providing augmented motion precision and manipulation
      dexterity. This article reviews the robotic systems recently developed for SPL
      and NOTES. MATERIAL AND METHODS: A literature search was conducted based on
      Science Citation Index, Engineering Index, Medline, and PubMed databases.
      RESULTS: Eleven robotic systems for SPL and six robotic systems for NOTES were
      identified. Structures and performances of these systems were reported. Special
      attention was directed to the systems using continuum mechanisms. DISCUSSION AND
      CONCLUSION: Regarding the structure aspect, the reviewed systems for SPL and
      NOTES all deploy a vision unit and at least two manipulation arms for surgical
      interventions through an access channel. To date, the smallest diameter of such a
      channel is 12 mm. Regarding the functionality aspect, only a few systems
      demonstrated results promising enough for animal or clinical studies in the near
      future. Surgical robots using dual continuum mechanisms achieved both design
      compactness and functional versatility. The characteristics suggest that the use
      of continuum mechanisms is worth exploring through future developments of
      surgical robots.

PMID- 25597630
TI  - Polypoid leiomyosarcoma of the esophagus treated by endoscopic submucosal
      dissection.
AB  - We report a rare case of polypoid leiomyosarcoma of the esophagus that was
      treated by endoscopic submucosal dissection (ESD). A 63-year-old man with
      complaints of progressive dysphagia was referred to Hyogo Cancer Center for
      treatment of esophageal tumor. Esophagoscopy revealed a polypoid tumor 25 mm in
      diameter on the left side of the upper esophagus. Despite several biopsy
      specimens, the diagnosis could not be confirmed. Computed tomography showed a
      protruded, homogeneously enhancing mass in the upper esophagus, but no lymph node
      enlargement or metastasis. After 1.5 months, the esophagogram showed a filling
      defect 47 mm in diameter in the upper esophagus. Given this rapid tumor growth,
      en bloc resection was done by ESD for therapeutic diagnosis. After this
      treatment, the tumor seemed to grow larger, showing a short stalk and occupying
      the esophageal lumen. Histopathologically, the tumor comprised pleomorphic
      spindle cells with mitosis. Tumor invasion involved the lumina propria mucosae
      and contact with the muscularis mucosae, but not involving the submucosa.
      Immunohistochemical examination showed positive staining for smooth muscle actin
      and HHF35, but negative for desmin, caldesmon, CD34, c-kit, DOG1, ALK, S-100
      protein and cytokeratin. These histopathological findings were compatible with a
      diagnosis of esophageal leiomyosarcoma derived from the muscularis mucosae.

PMID- 25597632
TI  - Effect of thyroid state on enzymatic and non-enzymatic processes in H2O2 removal
      by liver mitochondria of male rats.
AB  - We investigated thyroid state effect on capacity of rat liver mitochondria to
      remove exogenously produced H2O2, determining their ability to decrease
      fluorescence generated by an H2O2 detector system. The rate of H2O2 removal by
      both non respiring and respiring mitochondria was increased by hyperthyroidism
      and decreased by hypothyroidism. However, the rate was higher in the presence of
      respiratory substrates, in particular pyruvate/malate, indicating a respiration
      dependent process. Generally, the changes in H2O2 removal rates mirrored those in
      H2O2 release rates excluding the possibility that endogenous and exogenous H2O2
      competed for the removing system. Pharmacological inhibition revealed thyroid
      state-linked differences in antioxidant enzyme contribution to H2O2 removal which
      were consistent with those in antioxidant system activities. The H2O2 removal was
      only in part due to enzymatic systems and that imputable to non-enzymatic
      processes was higher in hyperthyroid and lower in hypothyroid mitochondria. The
      levels of cytochrome c and the light emissions, due to luminol oxidation
      catalyzed by cytochrome/H2O2, exhibited similar changes with thyroid state
      supporting the idea that non-enzymatic scavenging was mainly due to hemoprotein
      action, which produces hydroxyl radicals. Further support was obtained showing
      that the whole antioxidant capacity, which provides an evaluation of capacity of
      the systems, different from cytochromes, assigned to H2O2 scavenging, was lower
      in hyperthyroid than in hypothyroid state. In conclusion, our results show that
      mitochondria from hyperthyroid liver have a high capacity for H2O2 removal,
      which, however, leading in great part to more reactive oxygen species, results
      harmful for such organelles. 

PMID- 25597631
TI  - Annexin A2 promotes phagophore assembly by enhancing Atg16L+ vesicle biogenesis
      and homotypic fusion.
AB  - Plasma membrane budding of Atg-16L-positive vesicles represents a very early
      event in the generation of the phagophore and in the process of macroautophagy.
      Here we show that the membrane curvature-inducing protein annexin A2 contributes
      to the formation of these vesicles and their fusion to form phagophores.
      Ultrastructural, proteomic and FACS analyses of Atg16L-positive vesicles reveal
      that 30% of Atg16L-positive vesicles are also annexin A2-positive. Lipidomic
      analysis of annexin A2-deficient mouse cells indicates that this protein plays a
      role in recruiting phosphatidylserine and phosphatidylinositides to Atg16L
      positive vesicles. Absence of annexin A2 reduces both vesicle formation and
      homotypic Atg16L vesicle fusion. Ultimately, a reduction in LC3 flux and
      dampening of macroautophagy are observed in dendritic cells from Anxa2(-/-) mice.
      Together, our analyses highlight the importance of annexin A2 in vesiculation of
      a population of Atg16L-positive structures from the plasma membrane, and in their
      homotypic fusion to form phagophore structures. 

PMID- 25597633
TI  - Estrogen receptor alpha phosphorylation and its functional impact in human breast
      cancer.
AB  - Estrogen receptor alpha (ERalpha) is a member of the nuclear receptor superfamily
      of transcription factors that regulates cell proliferation, differentiation and
      homeostasis in various tissues. Sustained exposure to estrogen/estradiol (E2)
      increases the risk of breast, endometrial and ovarian cancers. ERalpha function
      is also regulated by phosphorylation through various kinase signaling pathways
      that will impact various ERalpha functions including chromatin interaction,
      coregulator recruitment and gene expression, as well impact breast tumor
      growth/morphology and breast cancer patient response to endocrine therapy.
      However, many of the previously characterized ERalpha phosphorylation sites do
      not fully explain the impact of receptor phosphorylation on ERalpha function.
      This review discusses work from our laboratory toward understanding a role of
      ERalpha site-specific phosphorylation in ERalpha function and breast cancer. The
      key findings discussed in this review are: (1) the effect of site specific
      ERalpha phosphorylation on temporal recruitment of ERalpha and unique coactivator
      complexes to specific genes; (2) the impact of stable disruption of ERalpha S118
      and S167 phosphorylation in breast cancer cells on eliciting unique gene
      expression profiles that culminate in significant effects on breast cancer
      growth/morphology/migration/invasion; (3) the Src kinase signaling pathway that
      impacts ERalpha phosphorylation to alter ERalpha function; and (4) circadian
      disruption by light exposure at night leading to elevated ERK1/2 and Src kinase
      and phosphorylation of ERalpha, concomitant with tamoxifen resistance in breast
      tumor models. Results from these studies demonstrate that even changes to single
      ERalpha phosphorylation sites can have a profound impact on ERalpha function in
      breast cancer. Future work will extend beyond single site phosphorylation
      analysis toward identification of specific patterns/profiles of ERalpha
      phosphorylation under different physiological/pharmacological conditions to
      understand how common phosphorylation profiles in breast cancer program specific
      physiological endpoints such as growth, apoptosis, migration/invasion, and
      endocrine therapy response. 

PMID- 25597634
TI  - Relative contribution of P450c17 towards the acute cortisol response: Lessons
      from sheep and goats.
AB  - The rapid release of cortisol from the adrenal cortex upon ACTH receptor
      activation plays an integral role in the stress response. It has been suggested
      that the quantitative control over adrenal steroidogenesis (quantity of total
      steroids produced) depends on the activities of cytochrome P450 side-chain
      cleavage and steroidogenic acute regulatory protein that supplies pregnenolone
      precursor to the pathway. The qualitative control (which steroids) then depends
      on the downstream steroidogenic enzymes, including cytochrome P450 17alpha
      hydroxylase/17,20-lyase (P450c17). In this review we focus on the relative
      contribution of P450c17 in the qualitative control of cortisol production with
      data collected from studies on South African Angora and Boer goats, as well as
      Merino sheep. Unique P450c17 genotypes were identified in these breeds with
      isoforms differing only with a couple of single amino acid residue substitutions.
      This review demonstrates how molecular and cellular differences relating to
      P450c17 activity can affect physiological and behavioural responses.

PMID- 25597635
TI  - An enzyme cascade synthesis of epsilon-caprolactone and its oligomers.
AB  - Poly-epsilon-caprolactone (PCL) is chemically produced on an industrial scale in
      spite of the need for hazardous peracetic acid as an oxidation reagent. Although
      Baeyer-Villiger monooxygenases (BVMO) in principle enable the enzymatic synthesis
      of epsilon-caprolactone (epsilon-CL) directly from cyclohexanone with molecular
      oxygen, current systems suffer from low productivity and are subject to substrate
      and product inhibition. The major limitations for such a biocatalytic route to
      produce this bulk chemical were overcome by combining an alcohol dehydrogenase
      with a BVMO to enable the efficient oxidation of cyclohexanol to epsilon-CL. Key
      to success was a subsequent direct ring-opening oligomerization of in situ formed
      epsilon-CL in the aqueous phase by using lipase A from Candida antarctica, thus
      efficiently solving the product inhibition problem and leading to the formation
      of oligo-epsilon-CL at more than 20 g L(-1) when starting from 200 mM
      cyclohexanol. This oligomer is easily chemically polymerized to PCL. 

PMID- 25597636
TI  - Management of acne scars: fulfilling our duty of care for patients.
AB  - Inflammatory lesions commonly associated with acne have a propensity to form
      scars which can substantially impact an individual's quality of life. As a result
      of variations in collagen levels during the wound-healing process, different
      types of scars can form requiring a tailored approach to treatment; treatment
      success depends on the modality of the treatment chosen. Here, I briefly discuss
      the different acne scar types, and their relationship with skin anatomy and
      histology, in relation to the different treatment options available. This paper
      was developed to accompany my state of the art presentation at 'The Changing
      Faces of Acne' meeting in June 2014 and I aim to share my personal experiences in
      order to offer guidance for appropriate treatment decisions. 

PMID- 25597637
TI  - IRF8 acts in lineage-committed rather than oligopotent progenitors to control
      neutrophil vs monocyte production.
AB  - Interferon regulatory factor 8 (IRF8) is a key regulator of myelopoiesis in mice
      and humans. IRF8-deficient mice exhibit increased neutrophil numbers but
      defective monocyte and dendritic cell (DC) production. It has therefore been
      hypothesized that IRF8 regulates granulocyte vs monocyte/DC lineage commitment by
      oligopotent progenitors. Alternatively, IRF8 could control the differentiation of
      lineage-committed progenitors. In this study, we defined the role of IRF8 in
      lineage commitment and neutrophil vs monocyte differentiation using a novel
      sorting strategy that for the first time allows us to separate oligopotent
      granulocyte-monocyte progenitors (GMPs) and their lineage-committed progeny:
      granulocyte progenitors (GPs) and monocyte progenitors (MPs). We show that IRF8
      is highly expressed by both GPs and MPs, but not GMPs, and is not required for GP
      or MP production by GMPs. In fact, IRF8-deficient mice have more GPs and MPs.
      This is not due to IRF8-mediated suppression of GP and MP production by GMPs, but
      rather to selective effects in GPs and MPs. We identify roles for IRF8 in
      regulating progenitor survival and differentiation and preventing leukemic cell
      accumulation. Thus, IRF8 does not regulate granulocytic vs monocytic fate in
      GMPs, but instead acts downstream of lineage commitment to selectively control
      neutrophil and monocyte production. 

PMID- 25597638
TI  - Functionalized nanoscale beta-1,3-glucan to improve Her2+ breast cancer therapy:
      In vitro and in vivo study.
AB  - We fabricated a targeted delivery system for doxorubicin (Dox) using beta-1,3
      glucan (Glu) as a carrier and decorated by trastuzumab antibody having the status
      of targeting agent against Her2+ breast tumors. Glu-Dox conjugates were also
      functionalized with polyethylenimine (PEI) intended for increasing specific
      cellular uptake of prepared nanoparticles. The self-assembled nanoparticles were
      prepared through conjugation of Dox- [Glu-Dox-] using succinic anhydride (Sa) in
      place of a linker. Nanoparticles had spherical morphology with positive zeta
      potential. In-vitro cell viability assay on two breast cancer cell lines
      demonstrated acceptable toxicity against tested cell lines. Confocal microscopic
      images demonstrated the remarkable cytoplasmic uptake of the nanoparticles in
      Her2-overexpressing 4T1 cells. A controlled release of Dox from Glu-Dox
      nanoparticles was investigated. In-vivo studies were performed on female Balb/C
      mice. The volume of the induced tumors was calculated following intravenous
      administration of nanoparticles. The tumor volume diminished efficiently and more
      rapidly after administration of nanoparticles containing Dox. Based on survival
      results, the formulation of Dox targeted nanoparticles appeared very promising
      for the treatment of tumors. It could be concluded that Glu-Dox targeted
      nanoparticles have potential advantages for delivering anticancer drugs to the
      target tissue. 

PMID- 25597639
TI  - Therapeutic hypothermia for hypoxic ischaemic encephalopathy using low-technology
      methods: a systematic review and meta-analysis.
AB  - A systematic review and meta-analysis were performed to determine the effect of
      therapeutic hypothermia using low-technology methods, in settings with facilities
      for intensive care, in term or near-term infants with hypoxic-ischaemic
      encephalopathy on mortality, neurological morbidity at discharge and neurological
      morbidity at 6-24 months. CONCLUSION: Meta-analysis of three randomised
      controlled studies showed that low-technology therapeutic hypothermia in an
      intensive care setting significantly reduced the mortality and the neurological
      morbidity in survivors at discharge.

PMID- 25597640
TI  - Influence of trial duration on the bias of the estimated treatment effect in
      clinical trials when individual heterogeneity is ignored.
AB  - In randomized clinical trials where the times to event of two treatment groups
      are compared under a proportional hazards assumption, it has been established
      that omitting prognostic factors from the model entails an underestimation of the
      hazards ratio. Heterogeneity due to unobserved covariates in cancer patient
      populations is a concern since genomic investigations have revealed molecular and
      clinical heterogeneity in these populations. In HIV prevention trials,
      heterogeneity is unavoidable and has been shown to decrease the treatment effect
      over time. This article assesses the influence of trial duration on the bias of
      the estimated hazards ratio resulting from omitting covariates from the Cox
      analysis. The true model is defined by including an unobserved random frailty
      term in the individual hazard that reflects the omitted covariate. Three frailty
      distributions are investigated: gamma, log-normal, and binary, and the asymptotic
      bias of the hazards ratio estimator is calculated. We show that the attenuation
      of the treatment effect resulting from unobserved heterogeneity strongly
      increases with trial duration, especially for continuous frailties that are
      likely to reflect omitted covariates, as they are often encountered in practice.
      The possibility of interpreting the long-term decrease in treatment effects as a
      bias induced by heterogeneity and trial duration is illustrated by a trial in
      oncology where adjuvant chemotherapy in stage 1B NSCLC was investigated. 

PMID- 25597641
TI  - Phlebotomus papatasi exposure cross-protects mice against Leishmania major co
      inoculated with Phlebotomus duboscqi salivary gland homogenate.
AB  - Leishmania parasites are inoculated into host skin together with sand fly saliva
      and multiple exposures to uninfected sand fly bites protect mice against
      Leishmania infection. However, sand fly vectors differ in composition of the
      saliva and therefore the protection elicited by their salivary proteins was shown
      to be species-specific. On the other hand, the optimal vaccine based on sand fly
      salivary proteins should be based on conserved salivary proteins conferring cross
      reactivity. In the present study we therefore focused on cross-protective
      properties of saliva from Phlebotomus papatasi and Phlebotomus duboscqi, the two
      natural vectors of Leishmania major. Two groups of mice exposed to bites of P.
      papatasi and two control, non-immunized groups were infected with L. major
      promastigotes along with either P. papatasi or P. duboscqi salivary gland
      homogenate. All mice were followed for the development of Leishmania lesions,
      parasite burdens, specific antibodies, and for production of NO, urea, or
      cytokines by peritoneal macrophages. Protection against Leishmania infection was
      observed not only in exposed mice challenged with homologous saliva but also in
      the group challenged with P. duboscqi saliva. Comparing both exposed groups, no
      significant differences were observed in parasite load, macrophage activity, or
      in the levels of anti-L. major and anti-P. papatasi/P. duboscqi antibodies. This
      is the first study showing cross-protection caused by salivary antigens of two
      Phlebotomus species. The cross-protective effect suggests that the anti
      Leishmania vaccine based on P. papatasi salivary proteins might be applicable
      also in areas where L. major is transmitted by P. duboscqi.

PMID- 25597644
TI  - English language skills requirements for internationally educated nurses working
      in the care industry: Barriers to UK registration or institutionalised
      discrimination?

PMID- 25597643
TI  - Conjugated fatty acids and methane production by rumen microbes when incubated
      with linseed oil alone or mixed with fish oil and/or malate.
AB  - We hypothesized that manipulating metabolism with fish oil and malate as a
      hydrogen acceptor would affect the biohydrogenation process of alpha-linolenic
      acid by rumen microbes. This study was to examine the effect of fish oil and/or
      malate on the production of conjugated fatty acids and methane (CH4 ) by rumen
      microbes when incubated with linseed oil. Linseed oil (LO), LO with fish oil (LO
      FO), LO with malate (LO-MA), or LO with fish oil and malate (LO-FO-MA) was added
      to diluted rumen fluid, respectively. The LO-MA and LO-FO-MA increased pH and
      propionate concentration compared to the other treatments. LO-MA and LO-FO-MA
      reduced CH4 production compared to LO. LO-MA and LO-FO-MA increased the contents
      of c9,t11-conjugated linoleic acid (CLA) and c9,t11,c15-conjugated linolenic acid
      (CLnA) compared to LO. The content of malate was rapidly reduced while that of
      lactate was reduced in LO-MA and LO-FO-MA from 3 h incubation time. The fold
      change of the quantity of methanogen related to total bacteria was decreased at
      both 3 h and 6 h incubation times in all treatments compared to the control.
      Overall data indicate that supplementation of combined malate and/or fish oil
      when incubated with linseed oil, could depress methane generation and increase
      production of propionate, CLA and CLnA under the conditions of the current in
      vitro study. 

PMID- 25597645
TI  - Synthesis and anticancer activity evaluation of eta(5)-C5(CH3)4R ruthenium
      complexes bearing chelating diphosphine ligands.
AB  - The complexes [RuCp*(PP)Cl] (Cp* = C5Me5; [], PP = dppm; [], PP = Xantphos),
      [RuCp(#)(PP)Cl] (Cp(#) = C5Me4(CH2)5OH; [], PP = dppm; [], PP = Xantphos) and
      [RuCp*(dppm)(CH3CN)][SbF6] [] were synthesized and evaluated in vitro as
      anticancer agents. Compounds gave nanomolar IC50 values against normoxic A2780
      and HT-29 cell lines, and were also tested against hypoxic HT-29 cells,
      maintaining their high activity. Complex yielded an IC50 value of 0.55 +/- 0.03
      MUM under a 0.1% O2 concentration. 

PMID- 25597646
TI  - Diversity of lactic acid bacteria isolated from Brazilian water buffalo
      mozzarella cheese.
AB  - The water buffalo mozzarella cheese is a typical Italian cheese which has been
      introduced in the thriving Brazilian market in the last 10 y, with good
      acceptance by its consumers. Lactic acid bacteria (LAB) play an important role in
      the technological and sensory quality of mozzarella cheese. In this study, the
      aim was to evaluate the diversity of the autochthones viable LAB isolated from
      water buffalo mozzarella cheese under storage. Samples were collected in 3
      independent trials in a dairy industry located in the southeast region of Brazil,
      on the 28th day of storage, at 4 oC. The LAB were characterized by Gram staining,
      catalase test, capacity to assimilate citrate, and production of CO2 from
      glucose. The diversity of LAB was evaluated by RAPD-PCR (randomly amplified
      polymorphic DNA-polymerase chain reaction), 16S rRNA gene sequencing, and by
      Vitek 2 system. Twenty LAB strains were isolated and clustered into 12 different
      clusters, and identified as Streptococcus thermophilus, Enterococcus faecium,
      Enterococcus durans, Leuconostoc mesenteroides subsp. mesenteroides,
      Lactobacillus fermentum, Lactobacillus casei, Lactobacillus delbrueckii subsp.
      bulgaricus, and Lactobacillus helveticus. Enterococcus species were dominant and
      citrate-positive. Only the strains of L. mesenteroides subsp. mesenteroides and
      L. fermentum produced CO2 from glucose and were citrate-positive, while L. casei
      was only citrate positive. This is the first report which elucidates the LAB
      diversity involved in Brazilian water buffalo mozzarella cheese. Furthermore, the
      results show that despite the absence of natural whey cultures as starters in
      production, the LAB species identified are the ones typically found in mozzarella
      cheese. 

PMID- 25597647
TI  - Cardiac awake extracorporeal life support-bridge to decision?
AB  - Severe acute heart failure requires immediate intensive care unit (ICU)
      treatment, but prognosis and outcome of further treatment regimens largely
      depends on the preprocedural status of the patient. Especially, multiorgan
      failure including mechanical ventilation are unfavorable predictors of clinical
      outcome. Here, we report a strategy of immediate initiation of extracorporeal
      life support (ECLS) in awake and spontaneously breathing patients with acute
      heart failure to achieve early multiorgan recovery and gain sufficient time for
      further treatment planning. Twenty-three patients with severe cardiac failure
      refractory to standard medical management underwent ECLS treatment, after first
      clinical signs of cardiac failure appeared to avoid mechanical ventilation.
      Hemodynamic parameters and renal and liver functions were monitored. Outcome at 1
      and 6 months was determined. Patients 46.1 +/- 15.5 years of age were placed on
      ECLS due to various underlying diagnosis: ischemic heart disease (n = 6),
      dilatative cardiomyopathy (n = 4), myocarditis (n = 2), graft failure following
      heart transplantation (n = 6), or other diseases (n = 5). ECLS lasted 11.9 +/-
      12.9 days. Hemodynamic stabilization was achieved immediately after ECLS
      initiation. Vasopressors were reduced subsequently and the cardiac situation
      improved indicated by central venous saturation, which increased from 38.5 +/-
      11.3% before to 74.26 +/- 8.4% (P < 0.0001) 24 h after ECLS initiation.
      Similarly, serum lactate levels decreased from 4.7 +/- 4.6 to 1.7 +/- 1.51 mmol/L
      (P = 0.003). Cumulative 30-day survival was 87.5%, and 6-month survival was
      70.8%. In acute cardiac failure, early ECLS treatment is a safe, feasible
      treatment in awake patients allowing a gain of time for final decision. Moreover,
      this strategy avoids complications associated with sedation and mechanical
      ventilation and leads to recovery of secondary organ function, enabling
      destination therapy. 

PMID- 25597648
TI  - Public funded field trials with transgenic plants in Europe: a comparison between
      Germany and Switzerland.
AB  - Field trails are indispensable for the scientific analysis of risks and potential
      benefits of genetically modified plants (GMP). The dramatic reduction of field
      trials in the European Union (EU) coincides with increasing safety demands,
      decreases in funding, and changes in the European directives. In parallel,
      opposition from non-governmental organizations (NGOs) has grown, and public
      acceptance has decreased. The cultivation of events approved by the EU is still
      allowed in principle, nevertheless, at least in Germany, there is a de facto
      moratorium on cultivation. In Switzerland, where development was much more
      hesitant compared to Germany, field trials are now possible, and a protected site
      has been established by the government. Public acceptance for scientific trials
      in Switzerland has risen, despite the continued moratorium on the cultivation
      based on a referendum. 

PMID- 25597649
TI  - Principal cells in gastric neoplasia of fundic gland (chief cell predominant)
      type show characteristics of immature chief cells.

PMID- 25597651
TI  - Spontaneous ruptured dissection of the right common iliac artery in a patient
      with classic Ehlers-Danlos syndrome phenotype.
AB  - Unlike vascular Ehlers-Danlos syndrome (EDS), classic EDS is rarely associated
      with vascular manifestation. We report the case of a 39-year-old man who
      presented with acute abdominal pain. At the time of presentation, the patient was
      in hypovolemic shock, and computed tomography angiogram demonstrated common iliac
      artery dissection with rupture. He underwent an attempted endovascular repair
      that was converted to an open repair of a ruptured right common iliac artery
      dissection. Subsequent genetic testing revealed a substitution of arginine for
      cysteine in type I collagen, COL1A1 exon 14 c.934C>T mutation, consistent with a
      rare variant of classic EDS.

PMID- 25597652
TI  - Treatment options for late type III endoleaks after endovascular aneurysm repair.
AB  - Late type III endoleaks result from complete or partial separation of endograft
      device components. Component separation repressurizes the aortic sac and may
      result in aortic rupture. We report 4 cases of late type III endoleaks after
      initial successful endovascular aneurysm repair for abdominal aortic aneurysm.
      Our cases include 3 aortic cuff separations and 1 iliac limb separation. The
      average time before graft separation was 3.25 years with an average aneurysm size
      at re-presentation of 8.2 cm. Management of these complex cases will be
      discussed, the literature reviewed, and recommendations for treatment offered.

PMID- 25597653
TI  - In-plane and cross-plane thermal conductivities of molybdenum disulfide.
AB  - We investigate the in-plane and cross-plane thermal conductivities of molybdenum
      disulfide (MoS2) using non-equilibrium molecular dynamics simulations. We find
      that the in-plane thermal conductivity of monolayer MoS2 is about 19.76 W mK(-1).
      Interestingly, the in-plane thermal conductivity of multilayer MoS2 is
      insensitive to the number of layers, which is in strong contrast to the in-plane
      thermal conductivity of graphene where the interlayer interaction strongly
      affects the in-plane thermal conductivity. This layer number insensitivity is
      attributable to the finite energy gap in the phonon spectrum of MoS2, which makes
      the phonon-phonon scattering channel almost unchanged with increasing layer
      number. For the cross-plane thermal transport, we find that the cross-plane
      thermal conductivity of multilayer MoS2 can be effectively tuned by applying
      cross-plane strain. More specifically, a 10% cross-plane compressive strain can
      enhance the thermal conductivity by a factor of 10, while a 5% cross-plane
      tensile strain can reduce the thermal conductivity by 90%. Our findings are
      important for thermal management in MoS2 based nanodevices and for thermoelectric
      applications of MoS2. 

PMID- 25597650
TI  - Corticostriatal interactions in the generation of tic-like behaviors after local
      striatal disinhibition.
AB  - The pathophysiology of the tics that define Gilles de la Tourette syndrome (TS)
      is not well understood. Local disinhibition within the striatum has been
      hypothesized to play a pathogenic role. In support of this, experimental
      disinhibition by local antagonism of GABA-A receptors within the striatum
      produces tic-like phenomenology in monkey and rat. We replicated this effect in
      mice via local picrotoxin infusion into the dorsal striatum. Infusion of
      picrotoxin into sensorimotor cortex produced similar movements, accompanied by
      signs of behavioral activation; higher-dose picrotoxin in the cortex produced
      seizures. Striatal inhibition with local muscimol completely abolished tic-like
      movements after either striatal or cortical picrotoxin, confirming their
      dependence on the striatal circuitry; in contrast, cortical muscimol attenuated
      but did not abolish movements produced by striatal picrotoxin. Striatal glutamate
      blockade eliminated tic-like movements after striatal picrotoxin, indicating that
      glutamatergic afferents are critical for their generation. These studies
      replicate and extend previous work in monkey and rat, providing additional
      validation for the local disinhibition model of tic generation. Our results
      reveal a key role for corticostriatal glutamatergic afferents in the generation
      of tic-like movements in this model. 

PMID- 25597654
TI  - Tactile stimulation interventions: influence of stimulation parameters on
      sensorimotor behavior and neurophysiological correlates in healthy and clinical
      samples.
AB  - The pure exposure to extensive tactile stimulation, without the requirement of
      attention or active training, has been revealed to enhance sensorimotor
      functioning presumably due to an induction of plasticity in the somatosensory
      cortex. The induced effects, including increased tactile acuity and manual
      dexterity have repeatedly been observed in basic as well as clinical research.
      However, results vary greatly in respect to the strength and direction of the
      effects on the behavioral and on the brain level. Multiple evidences show that
      differences in the stimulation protocols (e.g., two vs. multiple stimulation
      sites) and parameters (e.g., duration, frequency, and amplitude) might contribute
      to this variability of effects. Nevertheless, stimulation protocols have not been
      comprehensively compared yet. Identifying favorable parameters for tactile
      stimulation interventions is especially important because of its possible
      application as a treatment option for patients suffering from sensory loss,
      maladaptive plasticity, or certain forms of motor impairment. This review aims to
      compare the effects of different tactile stimulation protocols and to assess
      possible implications for tactile interventions. Our goal is to identify ways of
      optimizing stimulation protocols to improve sensorimotor performance. To this
      end, we reviewed research on tactile stimulation in the healthy population, with
      a focus on the effectiveness of the applied parameters regarding
      psychophysiological measures. We discuss the association of stimulation-induced
      changes on the behavioral level with alterations in neural representations and
      response characteristics. 

PMID- 25597656
TI  - Localized connectivity in depression: a meta-analysis of resting state functional
      imaging studies.
AB  - Resting-state fMRI studies investigating the pathophysiology of depression have
      identified prominent abnormalities in large-scale brain networks. However, it is
      unclear if localized dysfunction of specialized brain regions contribute to
      network-level abnormalities. We employed a meta-analytical procedure and reviewed
      studies conducted in China investigating changes in regional homogeneity (ReHo),
      a measure of localized intraregional connectivity, from resting-state fMRI in
      depression. Exploiting the statistical power gained from pooled analysis, we also
      investigated the effects of age, gender, illness duration and treatment on ReHo.
      The medial prefrontal cortex (MPFC) showed the most robust and reliable increase
      in ReHo in depression, with greater abnormality in medication-free patients with
      multiple episodes. Brain networks that relate to this region have been identified
      previously to show aberrant connectivity in depression, and we propose that the
      localized neuronal inefficiency of MPFC exists alongside wider network level
      disruptions involving this region. 

PMID- 25597657
TI  - The potential risk assessment for different arsenic species in the aquatic
      environment.
AB  - The different toxicity characteristics of arsenic species result in discrepant
      ecological risk. The predicted no-effect concentrations (PNECs) 43.65, 250.18,
      and 2.00*10(3)MUg/L were calculated for As(III), As(V), and dimethylarsinic acid
      in aqueous phase, respectively. With these PNECs, the ecological risk from
      arsenic species in Pearl River Delta in China and Kwabrafo stream in Ghana was
      evaluated. It was found that the risk from As(III) and As(V) in the samples from
      Pearl River Delta was low, while much high in Kwabrafo stream. This study implies
      that ecological risk of arsenic should be evaluated basing on its species. 

PMID- 25597658
TI  - Synthesis of linear low-density polyethylene-g-poly (acrylic acid)-co
      starch/organo-montmorillonite hydrogel composite as an adsorbent for removal of
      Pb(IotaIota) from aqueous solutions.
AB  - The purpose of this work is to remove Pb(II) from the aqueous solution using a
      type of hydrogel composite. A hydrogel composite consisting of waste linear low
      density polyethylene, acrylic acid, starch, and organo-montmorillonite was
      prepared through emulsion polymerization method. Fourier transform infrared
      spectroscopy (FTIR), Solid carbon nuclear magnetic resonance spectroscopy
      (CNMR)), silicon(-29) nuclear magnetic resonance spectroscopy (Si NMR)), and X
      ray diffraction spectroscope ((XRD) were applied to characterize the hydrogel
      composite. The hydrogel composite was then employed as an adsorbent for the
      removal of Pb(II) from the aqueous solution. The Pb(II)-loaded hydrogel composite
      was characterized using Fourier transform infrared spectroscopy (FTIR)), scanning
      electron microscopy (SEM)), and X-ray photoelectron spectroscopy ((XPS)). From
      XPS results, it was found that the carboxyl and hydroxyl groups of the hydrogel
      composite participated in the removal of Pb(II). Kinetic studies indicated that
      the adsorption of Pb(II) followed the pseudo-second-order equation. It was also
      found that the Langmuir model described the adsorption isotherm better than the
      Freundlich isotherm. The maximum removal capacity of the hydrogel composite for
      Pb(II) ions was 430mg/g. Thus, the waste linear low-density polyethylene-g-poly
      (acrylic acid)-co-starch/organo-montmorillonite hydrogel composite could be a
      promising Pb(II) adsorbent. 

PMID- 25597659
TI  - Research and application of kapok fiber as an absorbing material: a mini review.
AB  - Kapok fiber corresponds to the seed hairs of the kapok tree (Ceiba pentandra),
      and is a typical cellulosic fiber with the features of thin cell wall, large
      lumen, low density and hydrophobic-oleophilic properties. As a type of renewable
      natural plant fiber, kapok fiber is abundant, biocompatible and biodegradable,
      and its full exploration and potential application have received increasing
      attention in both academic and industrial fields. Based on the structure and
      properties of kapok fiber, this review provides a summary of recent research on
      kapok fiber including chemical and physical treatments, kapok fiber-based
      composite materials, and the application of kapok fiber as an absorbent material
      for oils, metal ions, dyes, and sound, with special attention to its use as an
      oil-absorbing material, one predominant application of kapok fiber in the coming
      future. 

PMID- 25597655
TI  - A compensatory role for declarative memory in neurodevelopmental disorders.
AB  - Most research on neurodevelopmental disorders has focused on their abnormalities.
      However, what remains intact may also be important. Increasing evidence suggests
      that declarative memory, a critical learning and memory system in the brain,
      remains largely functional in a number of neurodevelopmental disorders. Because
      declarative memory remains functional in these disorders, and because it can
      learn and retain numerous types of information, functions, and tasks, this system
      should be able to play compensatory roles for multiple types of impairments
      across the disorders. Here, we examine this hypothesis for specific language
      impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive
      compulsive disorder. We lay out specific predictions for the hypothesis and
      review existing behavioral, electrophysiological, and neuroimaging evidence.
      Overall, the evidence suggests that declarative memory indeed plays compensatory
      roles for a range of impairments across all five disorders. Finally, we discuss
      diagnostic, therapeutic and other implications. 

PMID- 25597660
TI  - Relationship between types of urban forest and PM2.5 capture at three growth
      stages of leaves.
AB  - Particulate matter diameter <= 2.5 MUm (PM2.5) causes direct harm to human
      health. Finding forms of urban forest systems that with the ability to reduce the
      amount of particulate matter in air effectively is the aim of this study. Five
      commonly cultivated kinds of urban forest types were studied in Beijing city at
      three stages of leaf growth. Results show that the urban forest system is capable
      of storing and capturing dust from the air. The types of shrubs and broadleaf
      trees that have the ability to capture PM2.5 from the air are most effective when
      leaves have fully developed. In the leafless season, the conifer and mixed tree
      types are the most effective in removing dust from the air. For all kinds of
      forest types and stages of leaf growth, the PM2.5 concentration is highest in the
      morning but lower in the afternoon and evening. Grassland cannot control
      particles suspended in the air, but can reduce dust pollution caused by dust from
      the ground blown by the wind back into the air.

PMID- 25597661
TI  - Bioaugmentation of DDT-contaminated soil by dissemination of the catabolic
      plasmid pDOD.
AB  - A plasmid transfer-mediated bioaugmentation method for the enhancement of
      dichlorodiphenyltrichloroethane (DDT) degradation in soil was developed using the
      catabolic plasmid pDOD from Sphingobacterium sp. D-6. The pDOD plasmid could be
      transferred to soil bacteria, such as members of Cellulomonas, to form DDT
      degraders and thus accelerate DDT degradation. The transfer efficiency of pDOD
      was affected by the donor, temperature, moisture, and soil type. Approximately
      50.7% of the DDT in the contaminated field was removed 210 days after the
      application of Escherichia coli TG I (pDOD-gfp). The results suggested that
      seeding pDOD into soil is an effective bioaugmentation method for enhancing the
      degradation of DDT.

PMID- 25597662
TI  - Comparison of different combined treatment processes to address the source water
      with high concentration of natural organic matter during snowmelt period.
AB  - The source water in one forest region of the Northeast China had very high
      natural organic matter (NOM) concentration and heavy color during snowmelt
      period. The efficiency of five combined treatment processes was compared to
      address the high concentration of NOM and the mechanisms were also analyzed.
      Conventional treatment can hardly remove dissolved organic carbon (DOC) in the
      source water. KMnO4 pre-oxidization could improve the DOC removal to 22.0%. Post
      activated carbon adsorption improved the DOC removal of conventional treatment to
      28.8%. The non-sufficient NOM removal could be attributed to the dominance of
      large molecular weight organic matters in raw water, which cannot be adsorbed by
      the micropore upon activated carbon. O3+activated carbon treatment are another
      available technology for eliminating the color and UV254 in water. However, its
      performance of DOC removal was only 36.4%, which could not satisfy the
      requirement for organic matter. The limited ozone dosage is not sufficient to
      mineralize the high concentration of NOM. Magnetic ion-exchange resin combined
      with conventional treatment could remove 96.2% of color, 96.0% of UV254 and 87.1%
      of DOC, enabling effluents to meet the drinking water quality standard. The high
      removal efficiency could be explained by the negative charge on the surface of
      NOM which benefits the static adsorption of NOM on the anion exchange resin. The
      results indicated that magnetic ion-exchange resin combined with conventional
      treatment is the best available technology to remove high concentration of NOM. 

PMID- 25597664
TI  - Could wastewater analysis be a useful tool for China? - A review.
AB  - Analysing wastewater samples is an innovative approach that overcomes many
      limitations of traditional surveys to identify and measure a range of chemicals
      that were consumed by or exposed to people living in a sewer catchment area.
      First conceptualised in 2001, much progress has been made to make wastewater
      analysis (WWA) a reliable and robust tool for measuring chemical consumption
      and/or exposure. At the moment, the most popular application of WWA, sometimes
      referred as sewage epidemiology, is to monitor the consumption of illicit drugs
      in communities around the globe, including China. The approach has been largely
      adopted by law enforcement agencies as a device to monitor the temporal and
      geographical patterns of drug consumption. In the future, the methodology can be
      extended to other chemicals including biomarkers of population health (e.g.
      environmental or oxidative stress biomarkers, lifestyle indicators or medications
      that are taken by different demographic groups) and pollutants that people are
      exposed to (e.g. polycyclic aromatic hydrocarbons, perfluorinated chemicals, and
      toxic pesticides). The extension of WWA to a huge range of chemicals may give
      rise to a field called sewage chemical-information mining (SCIM) with unexplored
      potentials. China has many densely populated cities with thousands of sewage
      treatment plants which are favourable for applying WWA/SCIM in order to help
      relevant authorities gather information about illicit drug consumption and
      population health status. However, there are some prerequisites and uncertainties
      of the methodology that should be addressed for SCIM to reach its full potential
      in China. 

PMID- 25597663
TI  - Chemical and optical properties of aerosols and their interrelationship in winter
      in the megacity Shanghai of China.
AB  - A field campaign on air quality was carried out in Shanghai in winter of 2012.
      The concentrations of NO, NO2, NOx, SO2, CO, and PM2.5 increased during haze
      formation. The average masses of SO4(2-), NO3(-) and NH4(+) were 10.3, 11.7 and
      6.7 MUg/m(3) during the haze episodes, which exceeded the average (9.2, 7.9, and
      3.4 MUg/m(3)) of these components in the non-haze days. The mean values for the
      aerosol scattering coefficient (bsp), aerosol absorption coefficient (bap) and
      single scattering albedo (SSA) were 288.7, 27.7 and 0.91 Mm(-1), respectively. A
      bi-peak distribution was observed for the mass concentrations of CO, NO, NO2, and
      NOx. More sulfate was produced during daytime than that in the evening due to
      photochemical reactions. The mass concentration of NH4(+) achieved a small peak
      at noontime. NO3(-) showed lower concentrations in the afternoon and higher
      concentrations in the early morning. There were obvious bi-peak diurnal patterns
      for bsp and bap as well as SSA. bsp and bap showed a positive correlation with
      PM2.5 mass concentration. (NH4)2SO4, NH4NO3, organic mass, elemental carbon and
      coarse mass accounted for 21.7%, 19.3%, 31.0%, 9.3% and 12.3% of the total
      extinction coefficient during non-haze days, and 25.6%, 24.3%, 30.1%, 8.1% and
      8.2% during hazy days. Organic matter was the largest contributor to light
      extinction. The contribution proportions of ammonium sulfate and ammonium nitrate
      to light extinction were significantly higher during the hazy time than during
      the non-haze days.

PMID- 25597665
TI  - Controlling cyanobacterial blooms by managing nutrient ratio and limitation in a
      large hyper-eutrophic lake: Lake Taihu, China.
AB  - Excessive nitrogen (N) and phosphorus (P) loading of aquatic ecosystems is a
      leading cause of eutrophication and harmful algal blooms worldwide, and reducing
      nutrient levels in water has been a primary management objective. To provide a
      rational protection strategy and predict future trends of eutrophication in
      eutrophic lakes, we need to understand the relationships between nutrient ratios
      and nutrient limitations. We conducted a set of outdoor bioassays at the shore of
      Lake Taihu. It showed that N only additions induced phytoplankton growth but
      adding only P did not. Combined N plus P additions promoted higher phytoplankton
      biomass than N only additions, which suggested that both N and P were deficient
      for maximum phytoplankton growth in this lake (TN:TP=18.9). When nutrients are
      present at less than 7.75-13.95 mg/L TN and 0.41-0.74 mg/L TP, the deficiency of
      either N or P or both limits the growth of phytoplankton. N limitation then takes
      place when the TN:TP ratio is less than 21.5-24.7 (TDN:TDP was 34.2-44.3), and P
      limitation occurs above this. Therefore, according to this ratio, controlling N
      when N limitation exists and controlling P when P deficiency is present will
      prevent algal blooms effectively in the short term. But for the long term, a
      persistent dual nutrient (N and P) management strategy is necessary.

PMID- 25597666
TI  - Reduction of NO by CO using Pd-CeTb and Pd-CeZr catalysts supported on SiO2 and
      La2O3-Al2O3.
AB  - The catalytic activity of Pd catalysts supported on Ce0.73Tb0.27Ox/SiO2,
      Ce0.6Zr0.4Ox/SiO2, Ce0.73Tb0.27Ox/La2O3-Al2O3 and Ce0.6Zr0.4Ox/La2O3-Al2O3 was
      studied using the reduction of NO by CO. The catalysts were characterized by X
      ray fluorescence, surface area, X-ray diffraction, temperature-programmed
      reduction, CO chemisorption and oxygen storage capacity. Temperature-programmed
      reduction results indicated that Tb or Zr incorporation improves the reducibility
      and oxygen storage capacity. CO chemisorption data suggested the presence of
      large PdO particles due to the low CO/Pd ratio. No significant differences were
      obtained in light off temperatures (TLight off) for all Pd catalysts and the most
      active was 1.5%Pd/Ce0.6Zr0.4Ox/SiO2. 

PMID- 25597667
TI  - Development and case study of a science-based software platform to support policy
      making on air quality.
AB  - This article describes the development and implementations of a novel software
      platform that supports real-time, science-based policy making on air quality
      through a user-friendly interface. The software, RSM-VAT, uses a response surface
      modeling (RSM) methodology and serves as a visualization and analysis tool (VAT)
      for three-dimensional air quality data obtained by atmospheric models. The
      software features a number of powerful and intuitive data visualization functions
      for illustrating the complex nonlinear relationship between emission reductions
      and air quality benefits. The case study of contiguous U.S. demonstrates that the
      enhanced RSM-VAT is capable of reproducing the air quality model results with
      Normalized Mean Bias <2% and assisting in air quality policy making in near real
      time. 

PMID- 25597668
TI  - Modulation of the DNA repair system and ATR-p53 mediated apoptosis is relevant
      for tributyltin-induced genotoxic effects in human hepatoma G2 cells.
AB  - The toxic effects of tributyltin (TBT) have been extensively documented in
      several types of cells, but the molecular mechanisms related to the genotoxic
      effects of TBT have still not been fully elucidated. Our study showed that
      exposure of human hepatoma G2 cells to 1-4 MUmol/L TBT for 3 hr caused severe DNA
      damage in a concentration-dependent manner. Moreover, the expression levels of
      key DNA damage sensor genes such as the replication factor C, proliferating cell
      nuclear antigen and poly (ADP-ribose) polymerase-1 were inhabited in a
      concentration-dependent manner. We further demonstrated that TBT induced cell
      apoptosis via the p53-mediated pathway, which was most likely activated by the
      ataxia telangiectasia mutated and rad-3 related (ATR) protein kinase. The results
      also showed that cytochrome c, caspase-3, caspase-8, caspase-9, and the B-cell
      lymphoma 2 were involved in this process. Taken together, we demonstrated for the
      first time that the inhibition of the DNA repair system might be more responsible
      for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced
      by TBT initiated ATR-p53-mediated apoptosis.

PMID- 25597669
TI  - Impact of dissolved organic matter on the photolysis of the ionizable antibiotic
      norfloxacin.
AB  - Norfloxacin (NOR), an ionizable antibiotic frequently used in the aquaculture
      industry, has aroused public concern due to its persistence, bacterial
      resistance, and environmental ubiquity. Therefore, we investigated the photolysis
      of different species of NOR and the impact of a ubiquitous component of natural
      water - dissolved organic matter (DOM), which has a special photochemical
      activity and normally acts as a sensitizer or inhibiter in the photolysis of
      diverse organics; furthermore, scavenging experiments combined with electron
      paramagnetic resonance (EPR) were performed to evaluate the transformation of NOR
      in water. The results demonstated that NOR underwent direct photolysis and self
      sensitized photolysis via hydroxyl radical (OH) and singlet oxygen ((1)O2) based
      on the scavenging experiments. In addition, DOM was found to influence the
      photolysis of different NOR species, and its impact was related to the
      concentration of DOM and type of NOR species. Photolysis of cationic NOR was
      photosensitized by DOM at low concentration, while zwitterionic and anionic NOR
      were photoinhibited by DOM, where quenching of OH predominated according to EPR
      experiments, accompanied by possible participation of excited triplet-state NOR
      and (1)O2. Photo-intermediate identification of different NOR species in
      solutions with/without DOM indicated that NOR underwent different
      photodegradation pathways including dechlorination, cleavage of the piperazine
      side chain and photooxidation, and DOM had little impact on the distribution but
      influenced the concentration evolution of photolysis intermediates. The results
      implied that for accurate ecological risk assessment of emerging ionizable
      pollutants, the impact of DOM on the environmental photochemical behavior of all
      dissociated species should not be ignored. 

PMID- 25597670
TI  - Enhanced bio-decolorization of 1-amino-4-bromoanthraquinone-2-sulfonic acid by
      Sphingomonas xenophaga with nutrient amendment.
AB  - Bacterial decolorization of anthraquinone dye intermediates is a slow process
      under aerobic conditions. To speed up the process, in the present study, effects
      of various nutrients on 1-amino-4-bromoanthraquinone-2-sulfonic acid (ABAS)
      decolorization by Sphingomonas xenophaga QYY were investigated. The results
      showed that peptone, yeast extract and casamino acid amendments promoted ABAS bio
      decolorization. In particular, the addition of peptone and casamino acids could
      improve the decolorization activity of strain QYY. Further experiments showed
      that l-proline had a more significant accelerating effect on ABAS decolorization
      compared with other amino acids. l-Proline not only supported cell growth, but
      also significantly increased the decolorization activity of strain QYY. Membrane
      proteins of strain QYY exhibited ABAS decolorization activities in the presence
      of l-proline or reduced nicotinamide adenine dinucleotide, while this behavior
      was not observed in the presence of other amino acids. Moreover, the positive
      correlation between l-proline concentration and the decolorization activity of
      membrane proteins was observed, indicating that l-proline plays an important role
      in ABAS decolorization. The above findings provide us not only a novel insight
      into bacterial ABAS decolorization, but also an l-proline-supplemented
      bioaugmentation strategy for enhancing ABAS bio-decolorization. 

PMID- 25597671
TI  - Winter survival of microbial contaminants in soil: an in situ verification.
AB  - The aim of the research was to evaluate, at site scale, the influence of freezing
      and freeze/thaw cycles on the survival of faecal coliforms and faecal enterococci
      in soil, in a climate change perspective. Before the winter period and during
      grazing, viable cells of faecal coliforms and faecal enterococci were detected
      only in the first 10 cm below ground, while, after the winter period and before
      the new seasonal grazing, a lower number of viable cells of both faecal
      indicators was detected only in some of the investigated soil profiles, and
      within the first 5 cm. Taking into consideration the results of specific
      investigations, we hypothesise that the non-uniform spatial distribution of grass
      roots within the studied soil can play an important role in influencing this
      phenomenon, while several abiotic factors do not play any significant role.
      Taking into account the local trend in the increase of air temperature, a
      different distribution of microbial pollution over time is expected in spring
      waters, in future climate scenarios. The progressive increase in air temperature
      will cause a progressive decrease in freeze/thaw cycles at higher altitudes,
      minimising cold shocks on microbial cells, and causing spring water pollution
      also during winter.

PMID- 25597672
TI  - Assessment of potential dermal and inhalation exposure of workers to the
      insecticide imidacloprid using whole-body dosimetry in China.
AB  - In China, although improvements to the pesticide registration process have been
      made in last thirty years, no occupational exposure data are required to obtain a
      commercial license for a pesticide product. Consequently, notably little research
      has been conducted to establish an exposure assessment procedure in China. The
      present study monitored the potential dermal operator exposure from knapsack
      electric sprayer wheat field application of imidacloprid in Liaocheng City,
      Shandong Province and in Xinxiang City, Henan Province, China, using whole-body
      dosimetry. The potential inhalation exposure was determined using a personal air
      pump and XAD-2 sample tubes. The analytical method was developed and validated,
      including such performance parameters as limits of detection and quantification,
      linear range, recovery and precision. The total potential dermal and inhalation
      exposures were 14.20, 16.80, 15.39 and 20.78 mL/hr, respectively, for the four
      operators in Liaocheng and Xinxiang, corresponding to 0.02% to 0.03% of the
      applied volume of spray solution. In all trials, the lower part (thigh, lower
      leg) of the body was the most contaminated, accounting for approximately 76% to
      88% of the total exposure. The inhalation exposure was less than 1% of the total
      exposure. Such factors as the application pattern, crop type, spray equipment,
      operator experience and climatic conditions have been used to explain the
      exposure distribution over the different parts of the body. As indicated by the
      calculated Margin of Exposure, the typical wheat treatment scenarios when a
      backpack sprayer was used are considered to be safe in terms of imidacloprid
      exposure.

PMID- 25597673
TI  - Biochemical and microbial soil functioning after application of the insecticide
      imidacloprid.
AB  - Imidacloprid is one of the most commonly used insecticides in agricultural
      practice, and its application poses a potential risk for soil microorganisms. The
      objective of this study was to assess whether changes in the structure of the
      soil microbial community after imidacloprid application at the field rate (FR,
      1mg/kg soil) and 10 times the FR (10* FR, 10mg/kg soil) may also have an impact
      on biochemical and microbial soil functioning. The obtained data showed a
      negative effect by imidacloprid applied at the FR dosage for substrate-induced
      respiration (SIR), the number of total bacteria, dehydrogenase (DHA), both
      phosphatases (PHOS-H and PHOS-OH), and urease (URE) at the beginning of the
      experiment. In 10* FR treated soil, decreased activity of SIR, DHA, PHOS-OH and
      PHOS-H was observed over the experimental period. Nitrifying and N2-fixing
      bacteria were the most sensitive to imidacloprid. The concentration of NO3(-)
      decreased in both imidacloprid-treated soils, whereas the concentration of NH4(+)
      in soil with 10* FR was higher than in the control. Analysis of the bacterial
      growth strategy revealed that imidacloprid affected the r- or K-type bacterial
      classes as indicated also by the decreased eco-physiological (EP) index.
      Imidacloprid affected the physiological state of culturable bacteria and caused a
      reduction in the rate of colony formation as well as a prolonged time for growth.
      Principal component analysis showed that imidacloprid application significantly
      shifted the measured parameters, and the application of imidacloprid may pose a
      potential risk to the biochemical and microbial activity of soils. 

PMID- 25597674
TI  - Comparison of three-dimensional fluorescence analysis methods for predicting
      formation of trihalomethanes and haloacetic acids.
AB  - This work investigated the application of several fluorescence excitation
      emission matrix analysis methods as natural organic matter (NOM) indicators for
      use in predicting the formation of trihalomethanes (THMs) and haloacetic acids
      (HAAs). Waters from four different sources (two rivers and two lakes) were
      subjected to jar testing followed by 24hr disinfection by-product formation tests
      using chlorine. NOM was quantified using three common measures: dissolved organic
      carbon, ultraviolet absorbance at 254 nm, and specific ultraviolet absorbance as
      well as by principal component analysis, peak picking, and parallel factor
      analysis of fluorescence spectra. Based on multi-linear modeling of THMs and
      HAAs, principle component (PC) scores resulted in the lowest mean squared
      prediction error of cross-folded test sets (THMs: 43.7 (MUg/L)(2), HAAs: 233.3
      (MUg/L)(2)). Inclusion of principle components representative of protein-like
      material significantly decreased prediction error for both THMs and HAAs.
      Parallel factor analysis did not identify a protein-like component and resulted
      in prediction errors similar to traditional NOM surrogates as well as
      fluorescence peak picking. These results support the value of fluorescence
      excitation-emission matrix-principal component analysis as a suitable NOM
      indicator in predicting the formation of THMs and HAAs for the water sources
      studied.

PMID- 25597675
TI  - The migration and transformation of dissolved organic matter during the freezing
      processes of water.
AB  - This study investigated the partitioning behavior of dissolved organic matter
      (DOM) in liquid and ice phases, as well as the changes in the optical properties
      and chlorine reactivity of DOM during the freezing processes of water. DOM was
      rejected from the ice phase and accumulated in the remaining liquid phase during
      water freezing. Moreover, the decrease in freezing temperature, as well as the
      increase in dissolved organic carbon (DOC) concentration of feed water, caused an
      increase in DOM captured in the ice phase. The ultraviolet-absorbing compounds,
      trihalomethane precursors, as well as fulvic acid- and humic acid-like
      fluorescent materials, were more liable to be to be rejected from the ice phase
      and were more easily retained in the unfrozen liquid phase during water freezing,
      as compared with organics (on average) that comprise DOC. In addition, it was
      also found a higher accumulation of these organics in the unfrozen liquid phase
      during water freezing at higher temperature. The freeze/thaw processes altered
      the quantity, optical properties, and chlorine reactivity of DOM. The decrease in
      ultraviolet light at 254 nm as well as the production of aromatic protein- and
      soluble microbial byproduct-like fluorescent materials in DOM due to freeze/thaw
      were consistently observed. On the other hand, the changes in DOC, trihalomethane
      formation potential, and fulvic acid- and humic acid-like fluorescence caused by
      freeze/thaw varied significantly between samples.

PMID- 25597676
TI  - Genomic analyses of metal resistance genes in three plant growth promoting
      bacteria of legume plants in Northwest mine tailings, China.
AB  - To better understand the diversity of metal resistance genetic determinant from
      microbes that survived at metal tailings in northwest of China, a highly elevated
      level of heavy metal containing region, genomic analyses was conducted using
      genome sequence of three native metal-resistant plant growth promoting bacteria
      (PGPB). It shows that: Mesorhizobium amorphae CCNWGS0123 contains metal
      transporters from P-type ATPase, CDF (Cation Diffusion Facilitator), HupE/UreJ
      and CHR (chromate ion transporter) family involved in copper, zinc, nickel as
      well as chromate resistance and homeostasis. Meanwhile, the putative CopA/CueO
      system is expected to mediate copper resistance in Sinorhizobium meliloti
      CCNWSX0020 while ZntA transporter, assisted with putative CzcD, determines zinc
      tolerance in Agrobacterium tumefaciens CCNWGS0286. The greenhouse experiment
      provides the consistent evidence of the plant growth promoting effects of these
      microbes on their hosts by nitrogen fixation and/or indoleacetic acid (IAA)
      secretion, indicating a potential in-site phytoremediation usage in the mining
      tailing regions of China. 

PMID- 25597677
TI  - Effect of environmental factors on the complexation of iron and humic acid.
AB  - A method of size exclusion chromatography coupled with ultraviolet
      spectrophotometry and off-line graphite furnace atomic absorption spectrometry
      was developed to assess the complexation properties of iron (Fe) and humic acid
      (HA) in a water environment. The factors affecting the complexation of Fe and HA,
      such as ionic strength, pH, temperature and UV radiation, were investigated. The
      Fe-HA complex residence time was also studied. Experimental results showed that
      pH could influence the deprotonation of HA and hydrolysis of Fe, and thus
      affected the complexation of Fe and HA. The complexation was greatly disrupted by
      the presence of NaCl. Temperature had some influence on the complexation. The
      yield of Fe-HA complexes showed a small decrease at high levels of UV radiation,
      but the effect of UV radiation on Fe-HA complex formation at natural levels could
      be neglected. It took about 10 hr for the complexation to reach equilibrium, and
      the Fe-HA complex residence time was about 20 hr. Complexation of Fe and HA
      reached a maximum level under the conditions of pH 6, very low ionic strength, in
      the dark and at a water temperature of about 25 degrees C, for 10 hr. It was
      suggested that the Fe-HA complex could form mainly in freshwater bodies and reach
      high levels in the warm season with mild sunlight radiation. With changing
      environmental parameters, such as at lower temperature in winter or higher pH and
      ionic strength in an estuary, the concentration of the Fe-HA complex would
      decrease.

PMID- 25597678
TI  - Resolving the influence of nitrogen abundances on sediment organic matter in
      macrophyte-dominated lakes, using fluorescence spectroscopy.
AB  - A controlled experiment was designed to resolve the influence of nitrogen
      abundance on sediment organic matters in macrophyte-dominated lakes using
      fluorescence analysis. Macrophyte biomass showed coincident growth trends with
      time, but different variation rates with nitrogen treatment. All plant growth
      indexes with nitrogen addition (N, NH4Cl 100, 200, 400mg/kg, respectively) were
      lower than those of the control group. Four humic-like components, two
      autochthonous tryptophan-like components, and one autochthonous tyrosine-like
      component were identified using the parallel factor analysis model. The results
      suggested that the relative component changes of fluorescence in the colonized
      sediments were in direct relation to the change of root biomass with time. In the
      experiment, the root formation parameters of the plants studied were
      significantly affected by adding N in sediments, which may be related to the
      reason that the root growth was affected by N addition. Adding a low
      concentration of N to sediments can play a part in supplying nutrients to the
      plants. However, the intensive uptake of NH4(+) may result in an increase in the
      intracellular concentration of ammonia, which is highly toxic to the plant cells.
      Hence, our experiment results manifested that organic matter cycling in the
      macrophyte-dominated sediment was influenced by nitrogen enrichment through
      influencing vegetation and relevant microbial activity. 

PMID- 25597679
TI  - Predicting heavy metals' adsorption edges and adsorption isotherms on MnO2 with
      the parameters determined from Langmuir kinetics.
AB  - Although surface complexation models have been widely used to describe the
      adsorption of heavy metals, few studies have verified the feasibility of modeling
      the adsorption kinetics, edge, and isotherm data with one pH-independent
      parameter. A close inspection of the derivation process of Langmuir isotherm
      revealed that the equilibrium constant derived from the Langmuir kinetic model,
      KS-kinetic, is theoretically equivalent to the adsorption constant in Langmuir
      isotherm, KS-Langmuir. The modified Langmuir kinetic model (MLK model) and
      modified Langmuir isotherm model (MLI model) incorporating pH factor were
      developed. The MLK model was employed to simulate the adsorption kinetics of
      Cu(II), Co(II), Cd(II), Zn(II) and Ni(II) on MnO2 at pH3.2 or 3.3 to get the
      values of KS-kinetic. The adsorption edges of heavy metals could be modeled with
      the modified metal partitioning model (MMP model), and the values of KS-Langmuir
      were obtained. The values of KS-kinetic and KS-Langmuir are very close to each
      other, validating that the constants obtained by these two methods are basically
      the same. The MMP model with KS-kinetic constants could predict the adsorption
      edges of heavy metals on MnO2 very well at different adsorbent/adsorbate
      concentrations. Moreover, the adsorption isotherms of heavy metals on MnO2 at
      various pH levels could be predicted reasonably well by the MLI model with the KS
      kinetic constants. 

PMID- 25597680
TI  - Applying a new method for direct collection, volume quantification and
      determination of N2 emission from water.
AB  - The emission of N2 is important to remove excess N from lakes, ponds, and
      wetlands. To investigate the gas emission from water, Gao et al. (2013) developed
      a new method using a bubble trap device to collect gas samples from waters.
      However, the determination accuracy of sampling volume and gas component
      concentration was still debatable. In this study, the method was optimized for in
      situ sampling, accurate volume measurement and direct injection to a gas
      chromatograph for the analysis of N2 and other gases. By the optimized new
      method, the recovery rate for N2 was 100.28% on average; the mean coefficient of
      determination (R(2)) was 0.9997; the limit of detection was 0.02%. We further
      assessed the effects of the new method, bottle full of water, vs. vacuum bag and
      vacuum vial methods, on variations of N2 concentration as influenced by sample
      storage times of 1, 2, 3, 5, and 7 days at constant temperature of 15 degrees C,
      using indices of averaged relative peak area (%) in comparison with the averaged
      relative peak area of each method at 0 day. The indices of the bottle full of
      water method were the lowest (99.5%-108.5%) compared to the indices of vacuum bag
      and vacuum vial methods (119%-217%). Meanwhile, the gas chromatograph
      determination of other gas components (O2, CH4, and N2O) was also accurate. The
      new method was an alternative way to investigate N2 released from various kinds
      of aquatic ecosystems.

PMID- 25597681
TI  - Effects of water management on arsenic and cadmium speciation and accumulation in
      an upland rice cultivar.
AB  - Pot and field experiments were conducted to investigate the effects of water
      regimes on the speciation and accumulation of arsenic (As) and cadmium (Cd) in
      Brazilian upland rice growing in soils polluted with both As and Cd. In the pot
      experiment constant and intermittent flooding treatments gave 3-16 times higher
      As concentrations in soil solution than did aerobic conditions but Cd showed the
      opposite trend. Compared to arsenate, there were more marked changes in the
      arsenite concentrations in the soil solution as water management shifted, and
      therefore arsenite concentrations dominated the As speciation and bioavailability
      in the soil. In the field experiment As concentrations in the rice grains
      increased from 0.14 to 0.21 mg/kg while Cd concentrations decreased from 0.21 to
      0.02 mg/kg with increasing irrigation ranging from aerobic to constantly flooding
      conditions. Among the various water regimes the conventional irrigation treatment
      produced the highest rice grain yield of 6.29 tons/ha. The As speciation analysis
      reveals that the accumulation of dimethylarsinic acid (from 11.3% to 61.7%) made
      a greater contribution to the increase in total As in brown rice in the
      intermittent and constant flooding treatments compared to the intermittent
      aerobic treatment. Thus, water management exerted opposite effects on Cd and As
      speciation and bioavailability in the soil and consequently on their accumulation
      in the upland rice. Special care is required when irrigation regime methods are
      employed to mitigate the accumulation of metal(loid)s in the grain of rice grown
      in soils polluted with both As and Cd.

PMID- 25597682
TI  - Acid-assisted hydrothermal synthesis of nanocrystalline TiO2 from titanate
      nanotubes: influence of acids on the photodegradation of gaseous toluene.
AB  - In order to efficiently remove volatile organic compounds (VOCs) from indoor air,
      one-dimensional titanate nanotubes (TiNTs) were hydrothermally treated to prepare
      TiO2 nanocrystals with different crystalline phases, shapes and sizes. The
      influences of various acids such as CH3COOH, HNO3, HCl, HF and H2SO4 used in the
      treatment were separately compared to optimize the performance of the TiO2
      nanocrystals. Compared with the strong and corrosive inorganic acids, CH3COOH was
      not only safer and more environmentally friendly, but also more efficient in
      promoting the photocatalytic activity of the obtained TiO2. It was observed that
      the anatase TiO2 synthesized in 15 mol/L CH3COOH solution exhibited the highest
      photodegradation rate of gaseous toluene (94%), exceeding that of P25 (44%) by a
      factor of more than two. The improved photocatalytic activity was attributed to
      the small crystallite size and surface modification by CH3COOH. The influence of
      relative humidity (20%-80%) on the performance of TiO2 nanocrystals was also
      studied. The anatase TiO2 synthesized in 15 mol/L CH3COOH solution was more
      tolerant to moisture than the other TiO2 nanocrystals and P25.

PMID- 25597683
TI  - Air-soil exchange of organochlorine pesticides in a sealed chamber.
AB  - So far little is known about air-soil exchange under any sealed circumstances
      (e.g., in plastic and glass sheds), which however has huge implications for the
      soil-air-plant pathways of persistent organic pollutants including organochlorine
      pesticides (OCPs). A newly designed passive air sampler was tested in a sealed
      chamber for measuring the vertical concentration profiles of gaseous phase OCPs
      (hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs)). Air
      was sampled at 5, 15, and 30 cm above ground level every 10th day during a 60-day
      period by deploying polyurethane foam cylinders housed in acrylonitrile butadiene
      styrene-covered cartridges. Concentrations and compositions of OCPs along the
      vertical sections indicated a clear relationship with proximity to the mixture of
      HCHs and DDTs which escapes from the soils. In addition, significant positive
      correlations were found between air temperatures and concentrations of HCHs and
      DDTs. These results indicated revolatilization and re-deposition being at or
      close to dynamic pseudo-equilibrium with the overlying air. The sampler used for
      addressing air-soil exchange of persistent organic pollutants in any sealed
      conditions is discussed.

PMID- 25597684
TI  - Effects of elevated CO2 on dynamics of microcystin-producing and non-microcystin
      producing strains during Microcystis blooms.
AB  - In an attempt to elucidate the effects of different CO2 concentrations (270, 380,
      and 750 MUL/L) on the competition of microcystin-producing (MC-producing) and non
      MC-producing Microcystis strains during dense cyanobacteria blooms, an in situ
      simulation experiment was conducted in the Meiliang Bay of Lake Taihu in the
      summer of 2012. The abundance of total Microcystis and MC-producing Microcystis
      genotypes was quantified based on the 16S rDNA and mcyD gene using real-time PCR.
      The results showed that atmospheric CO2 elevation would significantly decrease
      the pH value and increase the dissolved inorganic carbon (DIC) concentration.
      Changes in CO2 concentration did not show significant influence on the abundance
      of total Microcystis population. However, CO2 concentrations may be an important
      factor in determining the subpopulation structure of Microcystis. The enhancement
      of CO2 concentrations could largely increase the competitive ability of non-MC
      producing over MC-producing Microcystis, resulting in a higher proportion of non
      MC-producing subpopulation in treatments using high CO2 concentrations.
      Concurrently, MC concentration in water declined when CO2 concentrations were
      elevated. Therefore, we concluded that the increase of CO2 concentrations might
      decrease potential health risks of MC for human and animals in the future.

PMID- 25597685
TI  - Sulfide elimination by intermittent nitrate dosing in sewer sediments.
AB  - The formation of hydrogen sulfide in biofilms and sediments in sewer systems can
      cause severe pipe corrosions and health hazards, and requires expensive programs
      for its prevention. The aim of this study is to propose a new control strategy
      and the optimal condition for sulfide elimination by intermittent nitrate dosing
      in sewer sediments. The study was carried out based on lab-scale experiments and
      batch tests using real sewer sediments. The intermittent nitrate dosing mode and
      the optimal control condition were investigated. The results indicated that the
      sulfide-intermittent-elimination strategy by nitrate dosing is advantageous for
      controlling sulfide accumulation in sewer sediment. The oxidation-reduction
      potential is a sensitive indicator parameter that can reflect the control effect
      and the minimum N/S (nitrate/sulfide) ratio with slight excess nitrate is
      necessary for optimal conditions of efficient sulfide control with lower carbon
      source loss. The optimal control condition is feasible for the sulfide
      elimination in sewer systems. 

PMID- 25597686
TI  - Steel slag carbonation in a flow-through reactor system: the role of fluid-flux.
AB  - Steel production is currently the largest industrial source of atmospheric CO2.
      As annual steel production continues to grow, the need for effective methods of
      reducing its carbon footprint increases correspondingly. The carbonation of the
      calcium-bearing phases in steel slag generated during basic oxygen furnace (BOF)
      steel production, in particular its major constituent, larnite {Ca2SiO4}, which
      is a structural analogue of olivine {(MgFe)2SiO4}, the main mineral subjected to
      natural carbonation in peridotites, offers the potential to offset some of these
      emissions. However, the controls on the nature and efficiency of steel slag
      carbonation are yet to be completely understood. Experiments were conducted
      exposing steel slag grains to a CO2-H2O mixture in both batch and flow-through
      reactors to investigate the impact of temperature, fluid flux, and reaction
      gradient on the dissolution and carbonation of steel slag. The results of these
      experiments show that dissolution and carbonation of BOF steel slag are more
      efficient in a flow-through reactor than in the batch reactors used in most
      previous studies. Moreover, they show that fluid flux needs to be optimized in
      addition to grain size, pressure, and temperature, in order to maximize the
      efficiency of carbonation. Based on these results, a two-stage reactor consisting
      of a high and a low fluid-flux chamber is proposed for CO2 sequestration by steel
      slag carbonation, allowing dissolution of the slag and precipitation of calcium
      carbonate to occur within a single flow-through system. 

PMID- 25597687
TI  - Amine reclaiming technologies in post-combustion carbon dioxide capture.
AB  - Amine scrubbing is the most developed technology for carbon dioxide (CO2)
      capture. Degradation of amine solvents due to the presence of high levels of
      oxygen and other impurities in flue gas causes increasing costs and deterioration
      in long term performance, and therefore purification of the solvents is needed to
      overcome these problems. This review presents the reclaiming of amine solvents
      used for post combustion CO2 capture (PCC). Thermal reclaiming, ion exchange, and
      electrodialysis, although principally developed for sour gas sweetening, have
      also been tested for CO2 capture from flue gas. The three technologies all have
      their strengths and weaknesses, and further development is needed to reduce
      energy usage and costs. An expected future trend for amine reclamation is to
      focus on process integration of the current reclaiming technologies into the PCC
      process in order to drive down costs. 

PMID- 25597688
TI  - Do vehicular emissions dominate the source of C6-C8 aromatics in the megacity
      Shanghai of eastern China?
AB  - The characteristic ratios of volatile organic compounds (VOCs) to i-pentane, the
      indicator of vehicular emissions, were employed to apportion the vehicular and
      non-vehicular contributions to reactive species in urban Shanghai. Two kinds of
      tunnel experiments, one tunnel with more than 90% light duty gasoline vehicles
      and the other with more than 60% light duty diesel vehicles, were carried out to
      study the characteristic ratios of vehicle-related emissions from December 2009
      to January 2010. Based on the experiments, the characteristic ratios of C6-C8
      aromatics to i-pentane of vehicular emissions were 0.53 +/- 0.08 (benzene), 0.70
      +/- 0.12 (toluene), 0.41 +/- 0.09 (m,p-xylenes), 0.16 +/- 0.04 (o-xylene), 0.023
      +/- 0.011 (styrene), and 0.15 +/- 0.02 (ethylbenzene), respectively. The source
      apportionment results showed that around 23.3% of C6-C8 aromatics in urban
      Shanghai were from vehicular emissions, which meant that the non-vehicular
      emissions had more importance. These findings suggested that emission control of
      non-vehicular sources, i.e. industrial emissions, should also receive attention
      in addition to the control of vehicle-related emissions in Shanghai. The chemical
      removal of VOCs during the transport from emissions to the receptor site had a
      large impact on the apportionment results. Generally, the overestimation of
      vehicular contributions would occur when the VOC reaction rate constant with OH
      radicals (kOH) was larger than that of the vehicular indicator, while for species
      with smaller kOH than the vehicular indicator, the vehicular contribution would
      be underestimated by the method of characteristic ratios.

PMID- 25597689
TI  - Insights into metals in individual fine particles from municipal solid waste
      using synchrotron radiation-based micro-analytical techniques.
AB  - Excessive inter-contamination with heavy metals hampers the application of
      biological treatment products derived from mixed or mechanically-sorted municipal
      solid waste (MSW). In this study, we investigated fine particles of <2mm, which
      are small fractions in MSW but constitute a significant component of the total
      heavy metal content, using bulk detection techniques. A total of 17 individual
      fine particles were evaluated using synchrotron radiation-based micro-X-ray
      fluorescence and micro-X-ray diffraction. We also discussed the association,
      speciation and source apportionment of heavy metals. Metals were found to exist
      in a diffuse distribution with heterogeneous intensities and intense hot-spots of
      <10 MUm within the fine particles. Zn-Cu, Pb-Fe and Fe-Mn-Cr had significant
      correlations in terms of spatial distribution. The overlapped enrichment, spatial
      association, and the mineral phases of metals revealed the potential sources of
      fine particles from size-reduced waste fractions (such as scraps of organic
      wastes or ceramics) or from the importation of other particles. The diverse
      sources of heavy metal pollutants within the fine particles suggested that
      separate collection and treatment of the biodegradable waste fraction (such as
      food waste) is a preferable means of facilitating the beneficial utilization of
      the stabilized products.

PMID- 25597690
TI  - A simple modular aptasensor platform utilizing cucurbit[7]uril and a ferrocene
      derivative as an ultrastable supramolecular linker.
AB  - A simple modular aptamer-based sensor (aptasensor) platform was prepared by
      combining the merits of the rapid and efficient preparation of a self-assembled
      monolayer of cucurbit[7]uril (CB[7] SAM) and the strong and specific binding
      affinity of CB[7] to ferrocenemethylammonium (FA), as an ultrastable
      supramolecular linker, to immobilize aptamers on CB[7] SAM. 

PMID- 25597691
TI  - A foundation of excellence: honoring the contributions of early midwives.

PMID- 25597692
TI  - Chiral N,N'-dioxide-In(OTf)3-catalyzed asymmetric vinylogous Mukaiyama aldol
      reactions.
AB  - Chiral N,N'-dioxide-In(OTf)3 complexes were developed as efficient catalysts to
      catalyze the vinylogous Mukaiyama aldol reaction of the silyl dienol ester with
      aldehydes. The corresponding delta-hydroxy-alpha,beta-unsaturated esters were
      obtained in up to 99% yield and 98% ee. Moreover, the obtained (R)-3v can be
      easily transformed to natural bioactive products. 

PMID- 25597693
TI  - Protein denaturation at a single-molecule level: the effect of nonpolar
      environments and its implications on the unfolding mechanism by proteases.
AB  - Most proteins are typically folded into predetermined three-dimensional
      structures in the aqueous cellular environment. However, proteins can be exposed
      to a nonpolar environment under certain conditions, such as inside the central
      cavity of chaperones and unfoldases during protein degradation. It remains
      unclear how folded proteins behave when moved from an aqueous solvent to a
      nonpolar one. Here, we employed single-molecule atomic force microscopy and
      molecular dynamics (MD) simulations to investigate the structural and mechanical
      variations of a polyprotein, I278, during the change from a polar to a nonpolar
      environment. We found that the polyprotein was unfolded into an unstructured
      polypeptide spontaneously when pulled into nonpolar solvents. This finding was
      corroborated by MD simulations where I27 was dragged from water into a nonpolar
      solvent, revealing details of the unfolding process at the water/nonpolar solvent
      interface. These results highlight the importance of water in maintaining folding
      stability, and provide insights into the response of folded proteins to local
      hydrophobic environments. 

PMID- 25597694
TI  - Passenger comfort on high-speed trains: effect of tunnel noise on the subjective
      assessment of pressure variations.
AB  - When passing through a tunnel, aerodynamic effects on high-speed trains may
      impair passenger comfort. These variations in atmospheric pressure are
      accompanied by transient increases in sound pressure level. To date, it is
      unclear whether the latter influences the perceived discomfort associated with
      the variations in atmospheric pressure. In a pressure chamber of the DLR
      Institute of Aerospace Medicine, 71 participants (M = 28.3 years +/- 8.1 SD)
      rated randomised pressure changes during two conditions according to a crossover
      design. The pressure changes were presented together with tunnel noise such that
      the sound pressure level was transiently elevated by either +6 dB (low noise
      condition) or +12 dB (high noise condition) above background noise level (65
      dB(A)). Data were combined with those of a recent study, in which identical
      pressure changes were presented without tunnel noise (Schwanitz et al., 2013,
      'Pressure Variations on a Train - Where is the Threshold to Railway Passenger
      Discomfort?' Applied Ergonomics 44 (2): 200-209). Exposure-response relationships
      for the combined data set comprising all three noise conditions show that
      pressure discomfort increases with the magnitude and speed of the pressure
      changes but decreases with increasing tunnel noise. Practitioner Summary: In a
      pressure chamber, we systematically examined how pressure discomfort, as it may
      be experienced by railway passengers, is affected by the presence of tunnel noise
      during pressure changes. It is shown that across three conditions (no noise, low
      noise (+6 dB), high noise (+12 dB)) pressure discomfort decreases with increasing
      tunnel noise. 

PMID- 25597695
TI  - Proteomic analyses of membrane enriched proteins of Leishmania donovani Indian
      clinical isolate by mass spectrometry.
AB  - Visceral leishmaniasis (VL) is a major fatal disease prevalent in North-East
      India, caused by a protozoan parasite Leishmania donovani. The parasite
      multiplies and thrives inside mammalian macrophages and is transmitted by the
      bite of the sandfly. Due to the unsatisfactory treatment measures, increasing
      drug resistance and the advent of HIV-Leishmania co-infection there has been an
      urgent need to develop novel drug/vaccine targets against VL. Target
      identification is the key step in drug discovery and proteomics seems to be a
      suitable strategy for it due to the availability of Leishmania major, Leishmania
      infantum, Leishmania braziliensis, Leishmania donovani, Leishmania mexicana and
      Leishmania tarentolae genome sequence. Since, majority of proteome analyses of
      Leishmania have, so far, been performed on whole-cell extracts; this study is
      dealing with the sub-proteome analysis of the membrane-enriched protein (MEP)
      fractions of L. donovani. The analysis of 95 protein spots of the MEPs from two
      dimensional (2-D) gel image through matrix asserted laser desorption ionization
      time of flight/mass spectrometry (MALDI-TOF/MS) endorsed the identification of
      various relevant functional proteins. Out of 95 the MEP spots 72 have been
      identified and were classified on the basis of their biological function. Several
      proteins of unknown function that belong to different classes like cell
      signaling, transmembrane receptors, and transporters have been identified which
      could be the new potential therapeutic targets against VL in future. The proteome
      array of the MEPs contributes to further elucidation of the biological system of
      L. donovani as well as host-parasite relationships which may be further
      investigated for their crucial biological role in L. donovani for disease
      management. 

PMID- 25597697
TI  - Graphene on paper: a simple, low-cost chemical sensing platform.
AB  - Graphene layers have been transferred directly on to paper without any
      intermediate layers to yield G-paper. Resistive gas sensors have been fabricated
      using strips of G-paper. These sensors achieved a remarkable lower limit of
      detection of ~300 parts per trillion (ppt) for NO2, which is comparable to or
      better than those from other paper-based sensors. Ultraviolet exposure was found
      to dramatically reduce the recovery time and improve response times. G-paper
      sensors are also found to be robust against minor strain, which was also found to
      increase sensitivity. G-paper is expected to enable a simple and inexpensive low
      cost flexible graphene platform. 

PMID- 25597696
TI  - Measurement and analysis of the air pressure curve on the rigid lenses by use of
      ocular response analyzer.
AB  - PURPOSE: Pressure curves obtained from Ocular Response Analyzer (ORA) differ for
      the same patient in form and height. In some cases measurements on the subject
      show significant differences between recorded pressure curves. The purpose of the
      paper is to examine if the differences result from the corneal properties or from
      the device operation. METHODS: Examination of air pressure curves was carried out
      on four plano-convex glass lenses with radii of curvature close to the central
      corneal radius. Lenses were mounted in front of the air jet of the ORA analyzer.
      Series of 30 measurements on each lenses were recorded with 20 s and 60 s time
      interval between measurements. RESULTS were exported to computer and analyzed
      numerically. RESULTS: RESULTS show much higher reproducibility of pressure curves
      in every series of measurements in comparison to pressure curves recorded on the
      patients eye. This demonstrates that ORA produces air pulses with high
      reproducibility. CONCLUSIONS: Differences in air pressure pulses for the real eye
      can indicate the dynamics of ocular properties during measurements. Obtained
      pressure curves are not symmetrical and not well fitted by Gaussian curve. Type
      of asymmetry of air pressure curves may be explained by viscoelasticity of air.

PMID- 25597698
TI  - Intense photo- and tribo-luminescence of three tetrahedral manganese(II)
      dihalides with chelating bidentate phosphine oxide ligand.
AB  - Three air-stable tetrahedral manganese(ii) dihalide complexes [MnX2(DPEPO)]
      (DPEPO = bis[2-(diphenylphosphino)phenyl]ether oxide; X = Cl, Br and I) were
      prepared. All of the obtained compounds were structurally characterized by single
      crystal X-ray diffraction analyses, which reveal that they crystallize in
      centrosymmetric space groups and feature an isolated mononuclear structure with
      Mn(2+) in a tetrahedral environment. Interestingly, these complexes show
      excellent photoluminescent performance in neat solid form, with the highest total
      quantum yield (Phitotal) of up to 70% recorded for the dibromide complex. Intense
      green flashes of light could be observed by the naked eye when rubbing the
      manganese(ii) complexes. 

PMID- 25597699
TI  - Effect of single-dose Ginkgo biloba and Panax ginseng on driving performance.
AB  - CONTEXT: Panax ginseng and Gingko biloba are commonly used herbal supplements in
      the United States that have been reported to increase alertness and cognitive
      function. OBJECTIVE: The objective of this study was to investigate the effects
      of these specific herbals on driving performance. MATERIALS AND METHODS: 30
      volunteers were tested using the STISIM3(r) Driving Simulator (Systems Technology
      Inc., Hawthorne, CA, USA) in this double-blind, placebo-controlled study. The
      subjects were randomized into 3 groups of 10 subjects per group. After 10-min of
      simulated driving, subjects received either ginseng (1200 mg), Gingko (240 mg),
      or placebo administered orally. The test herbals and placebo were randomized and
      administered by a research assistant outside of the study to maintain blinding.
      One hour following administration of the herbals or placebo, the subjects
      completed an additional 10-min of simulated driving. Standard driving parameters
      were studied including reaction time, standard deviation of lateral positioning,
      and divided attention. Data collected for the divided attention parameter
      included time to response and number of correct responses. The data was analyzed
      with repeated-measures analysis of variance (ANOVA) and Kruskal-Wallis test using
      SPSS 22 (IBM, Armonk, NY, USA). RESULTS: There was no difference in reaction time
      or standard deviation of lateral positioning for both the ginseng and Ginkgo
      arms. For the divided attention parameter, the response time in the Ginkgo arm
      decreased from 2.9 to 2.5 s. The ginseng arm also decreased from 3.2 to 2.4 s.
      None of these values were statistically significant when between group
      differences were analyzed. DISCUSSION AND CONCLUSION: The data suggests there was
      no statistically significant difference between ginseng, Ginkgo or placebo on
      driving performance. We postulate this is due to the relatively small numbers in
      our study. Further study with a larger sample size may be needed in order to
      elucidate more fully the effects of Ginkgo and ginseng on driving ability.

PMID- 25597701
TI  - Note of concern.

PMID- 25597702
TI  - Retraction.

PMID- 25597700
TI  - Lymphangiogenesis is induced by mycobacterial granulomas via vascular endothelial
      growth factor receptor-3 and supports systemic T-cell responses against
      mycobacterial antigen.
AB  - Granulomatous inflammation is characteristic of many autoimmune and infectious
      diseases. The lymphatic drainage of these inflammatory sites remains poorly
      understood, despite an expanding understanding of lymphatic role in inflammation
      and disease. Here, we show that the lymph vessel growth factor Vegf-c is up
      regulated in Bacillus Calmette-Guerin- and Mycobacterium tuberculosis-induced
      granulomas, and that infection results in lymph vessel sprouting and increased
      lymphatic area in granulomatous tissue. The observed lymphangiogenesis during
      infection was reduced by inhibition of vascular endothelial growth factor
      receptor 3. By using a model of chronic granulomatous infection, we also show
      that lymphatic remodeling of tissue persists despite resolution of acute
      infection and a 10- to 100-fold reduction in the number of bacteria and tissue
      infiltrating leukocytes. Inhibition of vascular endothelial growth factor
      receptor 3 decreased the growth of new vessels, but also reduced the
      proliferation of antigen-specific T cells. Together, our data show that granuloma
      up-regulated factors increase granuloma access to secondary lymph organs by
      lymphangiogenesis, and that this process facilitates the generation of systemic T
      cell responses to granuloma-contained antigens. 

PMID- 25597703
TI  - Flicker electroretinograms before and after intravitreal ranibizumab injection in
      eyes with central retinal vein occlusion.
AB  - PURPOSE: To compare the amplitudes and implicit times of the flicker
      electroretinograms before and after an intravitreal injection of ranibizumab
      (IVR) in eyes with a central retinal vein occlusion (CRVO). METHODS: We reviewed
      the medical records of 15 consecutive patients who had macular oedema secondary
      to CRVO and had received an IVR at the Nagoya University Hospital from November
      2013 to July 2014. Flicker ERGs were recorded with both the RETeval(TM) system
      and a conventional ERG system before the IVR. One month after the IVR, recordings
      were repeated with only the RETeval(TM) system. RESULTS: The mean implicit times
      of the flicker ERGs of the affected eyes recorded with the RETeval(TM) system
      were significantly longer than that of the fellow eyes (32.2 +/- 2.6 msec versus
      28.1 +/- 1.2 msec, p < 0.001). One month after the IVR, the implicit times of the
      flicker ERGs of affected eyes were significantly shortened from 32.2 +/- 2.6 to
      30.6 +/- 2.2 msec (p < 0.001). CONCLUSIONS: The shortening of the implicit times
      of the flicker ERGs after the IVR indicates an improvement of retinal function
      after anti-VEGF therapy for CRVO eyes.

PMID- 25597704
TI  - Development and characterizations of a miniature capillary electrophoresis mass
      spectrometry system.
AB  - A miniature capillary electrophoresis mass spectrometry (CE/MS) system has been
      developed in this work. A 100% electrical driven miniaturized CE device was
      integrated with a miniature MS instrument, which has a discontinuous atmospheric
      pressure interface (DAPI) for coupling with atmospheric pressure ionization
      sources. A nanoelectrospray ionization (nano-ESI) source was developed with a
      sheath liquid interface for coupling the miniature CE and the MS system. A
      systematic characterization and optimization of the analytical performance have
      been done. The analysis of isobaric peptides and avoiding charge competition
      effects in nano-ESI sources have been demonstrated. 

PMID- 25597705
TI  - Absolute quantitative profiling of the key metabolic pathways in slow and fast
      skeletal muscle.
AB  - Slow and fast skeletal muscles are composed of, respectively, mainly oxidative
      and glycolytic muscle fibers, which are the basic cellular motor units of the
      motility apparatus. They largely differ in excitability, contraction mechanism,
      and metabolism. Because of their pivotal role in body motion and homeostasis, the
      skeletal muscles have been extensively studied using biochemical and molecular
      biology approaches. Here we describe a simple analytical and computational
      approach to estimate titers of enzymes of basic metabolic pathways and proteins
      of the contractile machinery in the skeletal muscles. Proteomic analysis of mouse
      slow and fast muscles allowed estimation of the titers of enzymes involved in the
      carbohydrate, lipid, and energy metabolism. Notably, we observed that differences
      observed between the two muscle types occur simultaneously for all proteins
      involved in a specific process such as glycolysis, free fatty acid catabolism,
      Krebs cycle, or oxidative phosphorylation. These differences are in a good
      agreement with the well-established biochemical picture of the muscle types. We
      show a correlation between maximal activity and the enzyme titer, suggesting that
      change in enzyme concentration is a good proxy for its catalytic potential in
      vivo. As a consequence, proteomic profiling of enzyme titers can be used to
      monitor metabolic changes in cells. Additionally, quantitative data of structural
      proteins allowed studying muscle type specific cell architecture and its
      remodeling. The presented proteomic approach can be applied to study metabolism
      in any other tissue or cell line. 

PMID- 25597706
TI  - Identification and characterization of a selective allosteric antagonist of human
      P2X4 receptor channels.
AB  - P2X4 is an ATP-gated nonselective cation channel highly permeable to calcium.
      There is increasing evidence that this homomeric purinoceptor, which is expressed
      in several neuronal and immune cell types, is involved in chronic pain and
      inflammation. The current paucity of unambiguous pharmacological tools available
      to interrogate or modulate P2X4 function led us to pursue the search for
      selective antagonists. In the high-throughput screen of a compound library, we
      identified the phenylurea BX430 (1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3
      pyridyl)urea, molecular weight = 413), with antagonist properties on human P2X4
      mediated calcium uptake. Patch-clamp electrophysiology confirmed direct
      inhibition of P2X4 currents by extracellular BX430, with submicromolar potency
      (IC50 = 0.54 uM). BX430 is highly selective, having virtually no functional
      impact on all other P2X subtypes, namely, P2X1-P2X3, P2X5, and P2X7, at 10-100
      times its IC50. Unexpected species differences were noticed, as BX430 is a potent
      antagonist of zebrafish P2X4 but has no effect on rat and mouse P2X4 orthologs.
      The concentration-response curve for ATP on human P2X4 in the presence of BX430
      shows an insurmountable blockade, indicating a noncompetitive allosteric
      mechanism of action. Using a fluorescent dye uptake assay, we observed that BX430
      also effectively suppresses ATP-evoked and ivermectin-potentiated membrane
      permeabilization induced by P2X4 pore dilation. Finally, in single-cell calcium
      imaging, we validated its selective inhibitory effects on native P2X4 channels at
      the surface of human THP-1 cells that were differentiated into macrophages. In
      summary, this ligand provides a novel molecular probe to assess the specific role
      of P2X4 in inflammatory and neuropathic conditions, where ATP signaling has been
      shown to be dysfunctional. 

PMID- 25597707
TI  - Categorization of multiple sclerosis relapse subtypes by B cell profiling in the
      blood.
AB  - INTRODUCTION: B cells are attracting increasing attention in the pathogenesis of
      multiple sclerosis (MS). B cell-targeted therapies with monoclonal antibodies or
      plasmapheresis have been shown to be successful in a subset of patients. Here,
      patients with either relapsing-remitting (n = 24) or secondary progressive (n =
      6) MS presenting with an acute clinical relapse were screened for their B cell
      reactivity to brain antigens and were re-tested three to nine months later.
      Enzyme-linked immunospot technique (ELISPOT) was used to identify brain-reactive
      B cells in peripheral blood mononuclear cells (PBMC) directly ex vivo and after
      96 h of polyclonal stimulation. Clinical severity of symptoms was determined
      using the Expanded Disability Status Scale (EDSS). RESULTS: Nine patients
      displayed B cells in the blood producing brain-specific antibodies directly ex
      vivo. Six patients were classified as B cell positive donors only after
      polyclonal B cell stimulation. In 15 patients a B cell response to brain antigens
      was absent. Based on the autoreactive B cell response we categorized MS relapses
      into three different patterns. Patients who displayed brain-reactive B cell
      responses both directly ex vivo and after polyclonal stimulation (pattern I) were
      significantly younger than patients in whom only memory B cell responses were
      detectable or entirely absent (patterns II and III; p = 0.003). In one patient a
      conversion to a positive B cell response as measured directly ex vivo and
      subsequently also after polyclonal stimulation was associated with the
      development of a clinical relapse. The evaluation of the predictive value of a
      brain antigen-specific B cell response showed that seven of eight patients
      (87.5%) with a pattern I response encountered a clinical relapse during the
      observation period of 10 months, compared to two of five patients (40%) with a
      pattern II and three of 14 patients (21.4%) with a pattern III response (p =
      0.0005; hazard ratio 6.08 (95% confidence interval 1.87-19.77). CONCLUSIONS: Our
      data indicate actively ongoing B cell-mediated immunity against brain antigens in
      a subset of MS patients that may be causative of clinical relapses and provide
      new diagnostic and therapeutic options for a subset of patients.

PMID- 25597708
TI  - A meta-analysis of re-treatment for intravenous immunoglobulin-resistant Kawasaki
      disease.
AB  - OBJECTIVE: To determine the optimal drug therapy for intravenous immunoglobulin
      resistant Kawasaki disease. METHODS: Studies regarding drug therapy for
      intravenous immunoglobulin-resistant Kawasaki disease were selected from medical
      electronic databases including PubMed, Medline, Elsevier, and Springer Link. The
      effectiveness in terms of temperature recovery and coronary artery damage was
      compared between a second intravenous immunoglobulin treatment and
      glucocorticosteroid treatment for children with intravenous immunoglobulin
      resistant Kawasaki disease using meta-analysis with Review Manager 5.3 software.
      Indices to evaluate the effects were body temperature, biomarker levels, and
      coronary artery lesions detected by echocardiography. Results are reported as
      relative risks or odds ratio with a 95% confidence interval and p<0.05. RESULTS:
      Meta-analysis included 52 patients in the second intravenous immunoglobulin
      treatment group and 75 patients in the glucocorticosteroid treatment control
      group from four studies that met our inclusion criteria. Temperatures of patients
      who received glucocorticosteroid treatment were effectively controlled compared
      with those who received a second intravenous immunoglobulin treatment (relative
      risk=0.73, 95% confidence interval: 0.58-0.92, p=0.007). There were no
      differences, however, in the incidence of coronary artery lesions between the two
      groups (odds ratio=1.55, 95% confidence interval: 0.57-4.20, p=0.39).
      CONCLUSIONS: Glucocorticosteroids are more effective in controlling body
      temperature compared with intravenous immunoglobulin re-treatment in intravenous
      immunoglobulin-resistant Kawasaki disease children; however, glucocorticosteroids
      and intravenous immunoglobulin re-treatment showed no difference in the
      prevention of coronary artery lesions.

PMID- 25597709
TI  - [Health in Peru].

PMID- 25597710
TI  - [Health reform in Peru: heading for the universal coverage].

PMID- 25597711
TI  - [Combination therapy of metformin vs dipeptidulpeptidase inhibitors and
      sulfonylureas in type 2 diabetes: clinical and economic impact].
AB  - OBJECTIVES: Determine the clinical repurcussions of adherence, metabolic control,
      hypoglycemia and cardiovascular events (CVE) and economics (resources and costs)
      in the combination therapy of metformin vs DPP-4 (dipeptidyl peptidase-4)
      inhibitors and sulfonylureas in patients with type 2 diabetes. Materials and
      methods. Observational-multicenter and retrospective design. We evaluated
      patients >= 30 years of age in treatment with metformin and who started a second
      oral antidiabetic treatment during 2008-2009. 2 study groups were established: a)
      metformin + DPP-4 inhibitors, and b) metformin + sulfonylurea. MAIN MEASURES:
      comorbidity, metabolic control (HbA1c <7%), compliance and complications
      (hypoglycemia, CVE). Follow up was conducted over two years. The cost model
      differentiated between direct healthcare costs (primary/ specialty care), and
      indirect costs (labor productivity). STATISTICAL ANALYSIS: logistic regression
      and ANCOVA models. Results. 1,405 patients were recruited (average age 67.1 years
      old; 56.2% male). 37.0% started a second treatment with DPP-4 inhibitors, and
      63.0% with sulfonylureas. After two years of follow up, patients treated with DPP
      4 inhibitors showed greater treatment adherence (70.3% vs. 60.6%; p <0.001);
      better metabolic control (64.3% vs. 60.6%; p<0.001), and a lower proportion of
      hypoglycemia (13.9% vs. 40.4%; p <0.001, respectively). The average/unit of
      adjusted total costs was ? 2,341 vs. ? 2,512; p = 0.038. CVE and renal failure
      rates were 3.7% vs. 6.4%; p = 0.027. Vildagliptin was the most used drug among
      DPP-4 inhibitors. Conclusions. Sulfonylureas were the most used drug for diabetes
      treatment. Patients treated with DPP-4 inhibitors had higher adherence and
      control of diabetes, with lower rates of hypoglycemia and CVE, resulting in lower
      healthcare costs.

PMID- 25597712
TI  - [Detection of Leishmania spp. based on the gene encoding HSP20].
AB  - OBJECTIVES: Explore a new target for molecular diagnosis of Leishmania. MATERIALS
      AND METHODS: We evaluated the utility of the gene that encodes the heat shock
      protein 20-kDa (Hsp20) for detecting Leishmania by polymerase chain reaction
      (PCR). PCR was normalized and analytical parameters were determined, as well as
      the validity and diagnostic accuracy, and concordance with the PCR - 18S. PCR
      Hsp20 with DNA was obtained from a group of clinical samples from different
      sources. RESULTS: The analytical parameters were adequate. The sensitivity
      obtained was 86% and the specificity was 100%. The concordance with the reference
      method was good (kappa = 0.731), which supports its potential use for diagnosis.
      The possibility of subsequent identification of the species by sequencing the
      amplified product gives an additional advantage. CONCLUSIONS: The usefulness of
      this gene as a new target for the detection of Leishmania was demonstrated.
      Because of its potential, it is recommended to improve the sensitivity of the
      method and to evaluate it in different endemic regions.

PMID- 25597713
TI  - [Western blot technique standardization for specific diagnosis of Chagas disease
      using excretory-secretory antigens of Trypanosoma cruzi epimastigotes].
AB  - OBJECTIVES: Evaluate the effectiveness of Western Blot for the specific diagnosis
      of Chagas disease using excretory-secretory antigens of Trypanosoma cruzi
      epimastigotes. MATERIALS AND METHODS: Antigens were obtained after twenty hours
      of incubation in Eagle?s Minimum Essential Medium, which were prepared at a
      protein concentration of 0.2 ug/uL to be faced with 10 mL pool of serum from
      patients with Chagas disease and a conjugated anti-IgG labeled with peroxidase.
      The presence of the following antigens was observed: 10, 12, 14, 15, 19, 20, 23,
      26, 30, 33, 36, 40, 42, 46, 58, 63, 69, 91, 100, and 112 kDa; of which antigens
      of 10, 12, 14, 15, 19, 20, 23, and 26 kDa were considered to be specific using
      pools of serum from patients with other parasitosis and serum from people with no
      parasites. The sensitivity of the technique was assessed using individual serum
      from 65 patients with Chagas disease; and the specificity with serum from 40
      patients with other parasitosis, and serums from five people who did not have
      parasites. RESULTS: The technique has a sensitivity of 95.4% in the detection of
      one to eight specific bands, a specificity of 100%, a positive predictive value
      of 100%, and a negative predictive value of 93.7%. CONCLUSIONS: Western Blot
      technique with excretory-secretory antigens of T. cruzi epimastigotes is
      effective in the diagnosis of Chagas disease in Peru; therefore, it can be used
      as a confirmatory test.

PMID- 25597715
TI  - [Availability of psychotropic medications in health care facilities of the
      Ministry of Health of Peru, 2011].
AB  - OBJECTIVES: Describe the availability of psychotropic medications for the
      treatment of mental disorders in the health care facilities of the Ministry of
      Health of Peru. MATERIALS AND METHODS: Monthly inventory reports of the
      availability and consumption of medications in facilities of the Ministry of
      Health during 2011 were analyzed. Using a cross sectional design, the
      availability of seven classes of psychotropic medications was determined. Also,
      the level of care of the establishments and the level of decisional autonomy to
      purchase medications were determined. RESULTS: Anti-anxiety medications were
      available in health facilities of all levels of care. Antidepressants and
      antipsychotics were available in about two thirds of hospitals and in less than
      20% of health centers and small health clinics. The other four classes of
      psychotropic medications (lithium, hypnotics and sedatives,
      psychostimulants/ADHD, and anti-dementia drugs) were only available in hospitals
      and not in health centers and small health clinics. 5% of hospitals had a
      sufficient supply to meet the demand for the year. CONCLUSIONS: There is a
      significant gap in the availability of psychotropic medications in the health
      care facilities of the Ministry of Health of Peru. This was observed both in
      hospitals and in primary care facilities. Actions are needed in health policy and
      management, including more funding and greater mental health training for staff
      in primary care, among other initiatives.

PMID- 25597714
TI  - [Prevalence of cardiovascular and metabolic risk factors in school students,
      university students, and women from community-based organizations in the
      districts of Lima, Callao, la Libertad and Arequipa, Peru 2011].
AB  - OBJECTIVES: To determine the prevalence of arterial hypertension, and
      cardiovascular and metabolic risk factors in school students, college students
      and women from community-based organizations (CBO) in four districts in Peru.
      MATERIALS AND METHODS: Cross-sectional study conducted in 2011 in the districts
      of Lima, Callao, La Libertad and Arequipa with school students, university
      students and women from CBOs. A survey, anthropometric measurements, blood
      pressure measurements and fasting blood sampling were conducted to determine
      glucose and lipid levels. Thus, prevalence of overweight, hypertension,
      hypercholesterolemia, suspected diabetes, and other variables, were calculated.
      The main outcome variable was prevalence of overweight. RESULTS: 1,127 people
      were included: 283 (25.1%) school students, 431 (38.3%) university students, and
      413 women (36.6%) from CBOs. Non-response rates were 3%, 0% and 8%, respectively.
      The average ages in the three groups were 14.3 +/- 0.9; 19.6 +/- 2.8; and 46.1 +/
      15.3 years, respectively. Prevalence of overweight/obesity (BMI >= 25) was
      11.3%, 20.9%, and 73.4%; hypertension was 0.7%; 1.2%, and 12.8%; high cholesterol
      (>= 200 mg/dL) was 5.2%, 11.5%, and 50.1%; and suspected diabetes was 1.4%; 1.0%,
      and 20.3% respectively in each group of school students, university students and
      women from CBOs. CONCLUSIONS: The prevalence of cardiovascular and metabolic risk
      factors generally increased in older age groups. In school and university aged
      groups, the most frequent problems were overweight and obesity, particularly
      abdominal obesity.

PMID- 25597716
TI  - [Acceptability of physical punishment in child rearing by people who were victims
      of physical violence during childhood in Peru].
AB  - OBJECTIVES: This study evaluated the association between having been a victim of
      physical violence during childhood and the acceptability, in later life, towards
      the use of physical punishment in child rearing. MATERIALS AND METHODS: A
      secondary analysis was conducted of a study on violence in 6,399 people over 14
      years of age living in the cities of Lima, Callao, Maynas, Arequipa, Cusco,
      Trujillo and Huamanga. Univariate and multivariate logistic regression models
      were used to estimate statistical associations. RESULTS: The acceptability of the
      use of physical punishment in child rearing is higher in people who were victims
      of physical abuse during childhood compared with non-victimized people (OR = 1.8;
      95% CI: 1.5-2 1; p <0.001) after adjusting for potential confounders.
      CONCLUSIONS: People exposed to physical violence during childhood are more likely
      to accept or justify violence in adulthood, which could help maintain this child
      rearing practice from one generation to the next. Initiatives aimed at preventing
      the use of physical punishment in child rearing should be implemented to reduce
      the tendency to reproduce the action of violence by victimized people.

PMID- 25597717
TI  - [Resistance to second-line anti-tuberculosis drugs among peruvian multidrug
      resistant Mycobacterium tuberculosis strains].
AB  - OBJECTIVES: To determine the drug resistance profiles for quinolones:
      ciprofloxacin (CFX), ofloxacin (OFX), moxifloxacin (MFX), and gatifloxacin (GFX);
      and for injectables: kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) in
      multidrug resistant (MDR) strains. We also investigated the correlation between
      mutations in rrs, tlyA and gyrA/B genes, and the in vitro resistance to the
      second-line anti-tuberculosis drugs. MATERIALS AND METHODS: In this pilot study
      we selected MDR clinical isolates collected from June-December 2004 in the
      Tropical Medicine Institute "Alexander von Humboldt" (Lima, Peru). The Minimum
      Inhibitory Concentration (MIC) of CFX, OFX, MFX, GFX, KAN, AMK and CAP for 14
      clinical isolates were determined and the sequences of rrs, tlyA and gyrA/B genes
      were analyzed by conventional PCR followed by sequencing. RESULTS: We obtained
      valid results for 11 samples. Four isolates were resistant to injectable drugs,
      and in all the cases the MICs were; >120 ug/mL for KAN and >160 ug/mL for AMK and
      CAP. Only 2 isolates were resistant to OFX with MIC = 4 ug/mL. Sequencing results
      suggested that the mutation A1401T in rrs gene could be the molecular cause of
      the resistance to injectable drugs. In this study we did not find any mutation in
      tlyA and gyrA/B associated to resistance. CONCLUSIONS: Our study suggests a
      possible association between the mutation A1401T in rrs and resistance to
      injectable drugs. However further studies should be done to confirm this
      hypothesis in Peru.

PMID- 25597718
TI  - [Effect of red maca (Lepidium meyenii) on INF-gamma levels in ovariectomized
      rats].
AB  - OBJECTIVES: Compare the effect of different doses of red maca on gamma interferon
      (IFN-gamma) levels in ovariectomized rats (OVX). MATERIALS AND METHODS: Adult
      female rats were randomly divided into the following six groups: Group 1: pseudo
      ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4
      ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts
      with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively.
      RESULTS: OVX rats showed low levels of IFN-gamma compared to PO rats. Estradiol
      and red maca reversed the effect of ovariectomy on the IFN-gamma levels. A
      positive dose-response effect of red maca on IFN-gamma levels was shown (r =
      0.57, p <0.05). CONCLUSIONS: Red maca administration increases levels of IFN
      gamma in ovariectomized rats.

PMID- 25597719
TI  - [Squamous neoplasia of the ocular surface in patients with pterygium in Peru].
AB  - OBJECTIVES: To estimate the frequency of unsuspected ocular surface squamous
      neoplasia (OSSN) in pterygium, the accuracy of clinical diagnosis, and associated
      demographic and clinical characteristics. MATERIALS AND METHODS: We reviewed
      histopathological reports of patients with a clinical diagnosis of pterygium
      and/or OSSN who were surgically treated between March 2009 and December 2012 at
      the National Eye Institute in Lima, Peru. The accuracy of the clinical diagnosis
      of OSSN was assessed by sensitivity, specificity, and likelihood ratios. Models
      of negative log-log regression were performed to identify demographic and
      clinical characteristics associated with increased odds of diagnosing OSSN.
      RESULTS: 3,021 histopathological reports were reviewed. The frequency of
      unsuspected OSSN in pterygium was 0.65%. Clinical diagnosis had a sensitivity of
      85%, a specificity of 99%, a positive likelihood ratio of 111.89, and a negative
      likelihood ratio of 0.15. Associated characteristics were male gender (OR =1.15;
      95% CI: 1.01 to 1.30), age group of 61-80 years (OR = 1.54, 95% CI: 1.28 to 1.85)
      >= 81 years (OR = 3.10; 95% CI: 2.09 to 4.58), presence of recurrent lesions (OR
      = 1.59; 95% CI: 1.03 to 2.46) and temporal location lesions (OR = 3.57; 95% CI:
      2.63 to 4.85). These characteristics were associated with a greater likelihood of
      OSSN. CONCLUSIONS: A low frequency of unsuspected OSSN was found; however, it is
      recommended to routinely perform histopathology studies to avoid misdiagnosis of
      OSSN as pterygium.

PMID- 25597720
TI  - [Levels of heavy metals in the environment and population exposure after five
      years of mineral exploration in the Las Bambas project, Peru 2010].
AB  - OBJECTIVES: Determine particulate matter (PM10) and heavy metals concentrations
      in the environment, as well as in surrounding communities of the Las Bambas
      project after five years of mineral exploration. MATERIALS AND METHODS: A
      comparative cross-sectional study was conducted in three districts in the area of
      influence of the Las Bambas project in Apurimac, Peru. Samples of water, air and
      soil were obtained to determine the concentrations of PM10 and heavy metals.
      Blood and urine samples were taken from 310 villagers to evaluate levels of lead,
      cadmium, arsenic and mercury. Results were compared with those obtained in 2005.
      RESULTS: Environmental concentrations of PM10 and heavy metals did not exceed the
      established reference values. The quality of drinking water and soil was not
      altered. Compared to the values found in 2005, the 2010 average levels of cadmium
      and mercury in urine increased significantly in the population of the districts
      of Chalhuahuacho (2.4 + 0.8 and 2.6 + 0.4), El Progreso (2.6 + 1.1 and 2.9 + 1.3)
      and Haquira (3.2 + 1.2 and 2.6 + 0.9). Cadmium values exceeded permissible
      limits. CONCLUSIONS: After five years of mineral exploration activity,
      environmental characteristics of the areas of influence of the Las Bambas mining
      project, have not been affected. However, changes are observed in the levels and
      percentage of people with cadmium in their urine.

PMID- 25597721
TI  - [Identification of proliferating cells in Taenia solium cysts].
AB  - Neoblasts are totipotent cells, solely responsible for the proliferation and
      maturation of tissues in free-living flatworms. Similar cells have been isolated
      from parasitic flatworms such as Echinococcus. Taenia solium causes human
      taeniasis (intestinal) and cysticercosis in humans and pigs. Brain infection with
      larvae (cysts) of T. solium results in neurocysticercosis which is hyperendemic
      in Peru, and its treatment is associated with serious neurological symptoms. The
      proliferative capacity and development stages of T. solium have not been
      described and the neoblasts of this parasite have not been characterized We
      looked for cell proliferation in T. solium cysts collected from an infected pig,
      which were identified when replicating and incorporating bromodeoxyuridine
      nucleotide detected with a monoclonal antibody. A stable cell line of neoblasts
      would be useful for systematic in vitro studies on drug efficacy and the biology
      of T. solium.

PMID- 25597722
TI  - [Sleep habits and traffic accidents in inter-provincial bus drivers of Arequipa,
      Peru].
AB  - In order to determine sleep habits in bus drivers and their relationship to
      accidents in the city of Arequipa, Peru, a cross-sectional descriptive study was
      conducted in a non-probabilistic sample of 166 drivers. Driving hours per day
      were 9.4 +/- 3.7. 54% (89) drive over 4 hours without stopping; 74% (123) drive
      at night; and 87% (145) sleep on the bus. 75% reported fatigue while driving
      (124). 27% (45) had drowsiness; 24% (40) reported having been in or on the verge
      of an accident while driving. Sleepiness or fatigue while driving was common in
      this population and their driving and rest habits could contribute to this.

PMID- 25597723
TI  - [Environmental impact of a public hospital in the city of Lima, Peru].
AB  - The operation of hospitals produces negative effects on the environment which
      contributes to air pollution and climate change. The institution in this study is
      a category III health care facility located in the city of Lima. It generates
      4.89 kg/bed/day of solid waste, and consumes 1.36 m3/bed/day of water; 25.22
      kWh/bed/day of electricity, and 2.76 liters/bed/day of fuel. The level of PM10
      and measured parameters of disposal to the public network are within legal
      limits, while mobile source noise exceeds the maximum allowable limit. The
      institution releases into the atmosphere 2,291 tons of CO2 equivalents per year.
      In conclusion, the institution studied generates a negative impact on the
      environment. 

PMID- 25597724
TI  - [Use of information sources by recently graduated physicians of Lima].
AB  - In order to determine the use of information sources by recently graduated
      physicians of Lima, Peru in 2011, a survey was conducted among graduated
      physicians at seven universities. They were asked about the use of search engines
      in the health area during their year of medical internship [last year of medical
      school]. Regular use was defined as the source being used once a week or daily.
      For 490 respondents, regularly used information sources were SciELO, accessed by
      173 (36.4%); PubMed 165 (34.4%); HINARI 117 (25.5%); UpToDate 98 (22.3%);
      Cochrane Library 94 (20.6%); LILACS 91 (19.8%); a hospital institutional library
      70 (15.0%); LIPECS 39 (8.7%); and Peru BVS 42 (9.3%). Only a minority regularly
      accessed information sources related to health. It is necessary to improve
      capacity in the efficient use of various resources of scientific information in a
      continuous way and that reaches students and health professionals.

PMID- 25597726
TI  - [Responsible management of dental amalgam mercury: a review of its impact on
      health].
AB  - This review discusses the implications of dental amalgam used in dentistry. We
      first focus on the status of the fetus, which is the most vulnerable to mercury
      exposure from maternal dental amalgams because of the chronic form and potential
      magnitude of exposure. And second, our work covers the awareness of environmental
      repercussions involved with continued use of this restorative material, a
      persistent, bioaccumulative and toxic chemical, when best management practices
      (BMPs) of mercury from the WHO and the American Dental Association are not
      followed. Although the use of dental amalgam is in decline in the public and
      private sectors, it is necessary that the measures disseminated by the WHO on
      BMPs are implemented by professional dentists and taught by academic institutions
      that may continue to teach its use. It is also essential to promote from the
      undergraduate level the ethical values and responsibility to health and the
      environment, considering that the poor handling of mercury contributes to the
      global burden of environmental mercury. Finally, the findings support important
      modifications in the clinical field, the principle of precaution, and logistical
      aspects of the profession in the process of reducing and eventually eliminating
      the use of mercury.

PMID- 25597725
TI  - [Mortality in traffic accidents in Bayamo, Cuba 2011].
AB  - With the objective of describing mortality from traffic accidents in Bayamo,
      Cuba, in 2011 a review was performed of injured and deceased patients due to
      traffic accidents, recorded in the Hospital Carlos M. de Cespedes. Of the 1,365
      injured patients treated in the emergency room, the predominant groups were
      individuals aged 25 to 44 years comprising 372 patients (27.3%) and men
      comprising 1,071 (78.5%). 46 people died, most from the same age group and male.
      Multiple traumatisms (52.6%) and craniofacial trauma (34.2%) were the predominant
      injuries. Motor vehicle-pedestrian accidents stood out with a mortality of 26.3%.
      In conclusion, mortality from traffic accidents predominately occurs in young
      male adults, whose fatal consequences are due to multiple traumatisms from road
      accidents.

PMID- 25597727
TI  - [Colombia: what has happened with its health reform?].
AB  - The health reform adopted in Colombia in 1993 was promoted by different agencies
      as the model to follow in matters of health policy. Following the guidelines of
      the Washington Consensus and the World Bank, the Government of Colombia, with the
      support of national political and economic elites, reorganized the management of
      health services based on market principles, dismantled the state system,
      increased finances of the sector, assigned the management of the system to the
      private sector, segmented the provision of services, and promoted interaction of
      actors in a competitive scheme of low regulation. After 20 years of
      implementation, the Colombian model shows serious flaws and is an object of
      controversy. The Government has weakened as the governing entity for health;
      private groups that manage the resources were established as strong centers of
      economic and political power; and violations of the right to health increased.
      Additionally, corruption and service cost overruns have put a strain on the
      sustainability of the system, and the state network is in danger of closing.
      Despite its loss of prestige at the internal level, various actors within and
      outside the country tend to keep the model based on contextual reforms.

PMID- 25597728
TI  - [Health system reforms in South America: an opportunity for UNASUR].
AB  - Health systems in South America still support segmentation, privatization and
      fragmentation. Health reforms of the structural adjustment programs in the 1980s
      and 1990s in South America followed different purposes and strategies ranging
      from privatization, commodification and state intervention for the implementation
      of a national public health service with universal access as a right of the
      citizens. Since the 2000s, many countries have expanded social policies, reduced
      poverty and social inequalities, and improved access to healthcare. This article
      proposes to discuss the health systems in South America from historical and
      political backgrounds, and the progress from the reforms in the last three
      decades. It also presents the three paradigmatic models of reform and their
      evolution, as well as the contrasts between universal coverage and universal
      systems. Finally, it presents current strengths and weaknesses of the twelve
      South American health systems as well as current opportunities and challenges in
      health for UNASUR.

PMID- 25597729
TI  - [The national health system in Peru].
AB  - In 1975, a group of professionals in Peru who were experts on national health
      systems began a process that led the country to be the first in South America to
      initiate a modern organization of the health system. This pioneering development
      meant that the creation of the National Health Services System [in Peru] in 1978
      occurred before the health system reforms in Chile (1980), Brazil (1990),
      Colombia (1993), and Ecuador (2008). This encouraging start has had permanent
      reformist fluctuations since then, with negative development because of the lack
      of a State policy. Current features of the Peruvian system are inefficient
      performance, discontinuity, and lack of assessment, which creates a major setback
      in comparison with other health systems in America. In the 21st century,
      significant technical efforts have been missed to modernize the system and its
      functions. The future is worrying and the role of new generations will be
      decisive.

PMID- 25597730
TI  - [Health reform in Ecuador: never again the right to health as a privilege].
AB  - The process of the health reform being experienced by Ecuador has had significant
      achievements because it occurs within the framework of a new Constitution of the
      Republic, which allowed the incorporation of historical social demands that arose
      from the criticism of neoliberalism in the restructure and modernization of the
      state. The backbone of the reform consists of three components: organization of a
      National Health System that overcomes the previous fragmentation and constitutes
      the Integral Public Health Network; development of policies to strengthen primary
      health care, articulating actions on the determinants of health, and finally,
      increasing funding to consolidate these changes. We conclude that challenges to
      the reform are related to the sustainability of the processes, financial
      sustainability of the system, greater activation of participatory mechanisms that
      enable citizen assessment of services and citizen empowerment regarding their
      right to health.

PMID- 25597731
TI  - [Intercultural aspects of the health system reform in Bolivia].
AB  - This article is a reflection on how interculturality, understood as the way to
      improve the health of the Bolivian population and coupled with the concept of
      living well, is not contributing to improving the quality of life and health of
      the most vulnerable populations in the country. The discourse is coupled with the
      intention of saving lives in its broadest sense; however, for this it is
      necessary to make decisions about environmental health and extractivist policies
      that are not taken into account in the health issues affecting indigenous
      communities, a population targeted by the intercultural aspects of the health
      reform. 

PMID- 25597732
TI  - [Public-private partnerships for health services: the solution for the peruvian
      health system?].
AB  - Private investor participation in the provision of public health care services
      (called ?public-private partnership? or PPP) dates from the last century, both in
      Latin America and Europe. In Peru, legislation for PPPs was published in 2008 in
      terms of infrastructure, maintenance and service provisions in general; but it
      was at the end of 2013 when PPP began to be implemented for health services. In
      Colombia, it was realized that this model was very costly. In Chile, the private
      sector was not regulated from the beginning and today it is difficult to
      regulate. Costa Rica never gave full decisional power to private sector; the
      responsibility for providing health services to its population and maintaining
      health as a right has always been maintained. In Peru, at this stage of PPPs
      implementation for health services, other experiences are not taken into account
      such as: transparency, participation of all stakeholders, development of specific
      legislation, among others. 

PMID- 25597733
TI  - [Analysis of the policy for tuberculosis control in Colombia].
AB  - The article aims to analyze the policies for the control of tuberculosis in
      Colombia between 1975 and 2010. During the 1980s, there was an effort in
      management of the control programs that was reflected in the reduction of
      incidence and mortality. Since 1993, when the National Health System was
      dismantled and resource management was privatized, the performance indicators of
      the control program showed significant deterioration. Since 2009 there has been
      an effort to clarify and strengthen the control policy of tuberculosis. However,
      the structure of the health model remains untouched and results don'?t show
      significant recovery that would allow by 2015 an increase in the notification and
      cure of at least 85% of patients with tuberculosis, and a reduction in incidence
      and mortality of 50%.

PMID- 25597734
TI  - [Mandatory requirement of social health service in Peru: discriminatory and
      unconstitutional].
AB  - The rural and urban-edge health service (SERUMS) is an activity that only health
      professionals perform for the Peruvian government, as it is a mandatory
      requirement to qualify for a second specialty or to work in public hospitals and
      public health care facilities, and obtain government scholarships for future
      training. The few legal changes in the rules of this social program and the focus
      of ?service? restricted to health professionals lead to a perception of this
      policy as discriminatory and unconstitutional because it violates the right to
      education and work. There is no scientific evidence that supports the usefulness
      and effectiveness of this program in terms of quality of service and health
      indicator improvement, as well as in adequate distribution and retention of
      health professionals. We suggest to abolish the compulsory requirement and to
      reformulate a political strategy to help attract and retain health professionals
      in vulnerable areas of Peru. 

PMID- 25597735
TI  - [Coinfection of Mycobacterium malmoense and Mycobacterium tuberculosis in a
      patient with acquired inmune deficiency syndrome].
AB  - A case is presented of coinfection with Mycobacterium malmoense and Mycobacterium
      tuberculosis in a Cuban patient with AIDS which produced respiratory and liver
      disease respectively. Cultures done from sputum samples showed the presence of a
      non-pigmented, slow growing mycobacterial strain belonging to Runyon group III
      and identified as Mycobacterium malmoense. From cultures of liver tissue removed
      laparoscopically, a strain was isolated and subsequently identified as
      Mycobacterium tuberculosis. Anatomapathologic examination confirmed the diagnosis
      of tuberculosis, the patient received specific treatment and had a favorable
      clinical course. This report of a rare case of coinfection of Mycobacterium
      describes the first report of hepatic tuberculosis in a patient with AIDS in
      Cuba. 

PMID- 25597736
TI  - [First report of alkaptonuria in Peru].
AB  - Alkaptonuria is an inborn error of metabolism caused by deficiency of
      homogentisate 1,2-dioxygenase (HGD) which produces an excess of homogentisic acid
      (HGA). A case is presented of a 57 year old woman whose urine has turned black
      since birth. For 9 years she presented a greenish pigmentation in her nail beds
      that did not improve with antifungal treatments, and in the last 9 months she
      showed worsening large joint osteoarthritis. This situation forced her to use a
      wheelchair due to the intense pain caused by osteoarthritis in her hips and
      lumbar spine. From the description of symptoms, her urinary HGA was measured
      which confirmed the diagnosis of alkaptonuria. Analgesics and a diet without
      tyrosine-containing products were suggested. The patient was also referred for
      hip replacement surgery. This is the first reported case of alkaptonuria in Peru.

PMID- 25597737
TI  - [Prominent personalities from the tropical dermatology field in Peru].
AB  - This article pays tribute to three Peruvian medical personalities: Jose Neyra
      Ramirez (1929-2012), Abelardo Tejada (1931-2013) and Oscar Romero Rivas (1929
      2011), highlighting their valuable contributions to the field of Tropical
      Dermatology and Health Medicine that benefited public health and Peruvian medical
      education. The article mentions the formation of a group of young researchers
      called ?The Anacoretas?, including professors Hugo Pesce, Enrique Encinas, Juan
      Francisco Valegas in Lima; and Enerst Nausk and Victor Manchego in Germany, who,
      with the support of the Peruvian and German governments promoted and created the
      first university research center of Tropical Medicine on the Pacific Coast of
      Latin America called Daniel A. Carrion Tropical Medicine Institute at Universidad
      Nacional Mayor de San Marcos in Lima (TMI/UNMSM).

PMID- 25597738
TI  - [Is health sector reform possible without academic development of the health
      system and with "multifunction?" health staff?].

PMID- 25597739
TI  - [New version of the Declaration of Helsinki: shortcomings to resolve].

PMID- 25597740
TI  - [Comments to the articles: "Annual prevalence of mental disorders and use of
      mental health services in Peru: results of theWorld Mental Health Study, 2005?"
      and "?Lifetime prevalence and age of onset of mental disorders in Peru: results
      of the World Mental Health Study, 2005"].

PMID- 25597741
TI  - [Comments to the articles: "Annual prevalence of mental disorders and use of
      mental health services in Peru: results of the World Mental Health Study, 2005"?
      and ?"Lifetime prevalence and age of onset of mental disorders in Peru: results
      of the World Mental Health Study, 2005"?--authors reply].

PMID- 25597742
TI  - [Financing rare or orphan diseases].

PMID- 25597744
TI  - ABC50 mutants modify translation start codon selection.
AB  - ATP-binding cassette 50 (ABC50; also known as ABCF1) binds to eukaryotic
      initiation factor 2 (eIF2) and is required for efficient translation initiation.
      An essential step of this process is accurate recognition and selection of the
      initiation codon. It is widely accepted that the presence and movement of eIF1,
      eIF1A and eIF5 are key factors in modulating the stringency of start-site
      selection, which normally requires an AUG codon in an appropriate sequence
      context. In the present study, we show that expression of ABC50 mutants, which
      cannot hydrolyse ATP, decreases general translation and relaxes the
      discrimination against the use of non-AUG codons at translation start sites.
      These mutants do not appear to alter the association of key initiation factors to
      40S subunits. The stringency of start-site selection can be restored through
      overexpression of eIF1, consistent with the role of that factor in enhancing
      stringency. The present study indicates that interfering with the function of
      ABC50 influences the accuracy of initiation codon selection. 

PMID- 25597743
TI  - Selection of nanobodies that block the enzymatic and cytotoxic activities of the
      binary Clostridium difficile toxin CDT.
AB  - The spore-forming gut bacterium Clostridium difficile is the leading cause of
      antibiotic-associated diarrhea in hospitalized patients. The major virulence
      factors are two large glucosylating cytotoxins. Hypervirulent strains (e.g.
      ribotype 027) with higher morbidity and mortality additionally produce the binary
      CDT toxin (Clostridium difficile transferase) that ADP-ribosylates actin and
      induces microtubule-based cell protrusions. Nanobodies are robust single domain
      antibodies derived from camelid heavy chain antibodies. Here we report the
      generation of functional nanobodies against the enzymatic CDTa and the heptameric
      receptor binding subunit CDTb. The nanobodies were obtained from a variable
      domain repertoire library isolated from llamas immunized with recombinant CDTa or
      CDTb. Five CDTa-specific nanobodies blocked CDTa-mediated ADP-ribosylation of
      actin. Three CDTa-specific and two CDTb-specific nanobodies neutralized the
      cytotoxicity of CDTa+b. These nanobodies hold promise as new tools for research,
      diagnosis and therapy of C. difficile associated disease. 

PMID- 25597745
TI  - A novel proteotoxic stress associated mechanism for macular corneal dystrophy.
AB  - Macular corneal dystrophy is a rare autosomal recessive eye disease affecting
      primarily the corneal stroma. Abnormal accumulation of proteoglycan aggregates
      has been observed intra- and extracellularly in the stromal layer. In addition to
      the stromal keratocytes and corneal lamellae, deposits are also present in the
      basal epithelial cells, endothelial cells and Descemet's membrane. Misfolding of
      proteins has a tendency to gather into aggregating deposits. We studied
      interaction of molecular chaperones and proteasomal clearance in macular
      dystrophy human samples and in human corneal HCE-2 epithelial cells. Seven cases
      of macular corneal dystrophy and four normal corneal buttons collected during
      corneal transplantation were examined for their expression patterns of heat shock
      protein 70, ubiquitin protein conjugates and SQSTM1/p62. In response to
      proteasome inhibition the same proteins were analyzed by western blotting. Slit
      lamp examination, in vivo confocal cornea microscopy and transmission electron
      microscopy were used for morphological analyses. Heat shock protein 70, ubiquitin
      protein conjugates and SQSTM1/p62 were upregulated in both the basal corneal
      epithelial cells and the stromal keratocytes in macular corneal dystrophy samples
      that coincided with an increased expression of the same molecules under
      proteasome inhibition in the HCE-2 cells in vitro. We propose a novel regulatory
      mechanism that connects the molecular chaperone and proteasomal clearance system
      in the pathogenesis of macular corneal dystrophy. 

PMID- 25597747
TI  - Pre-stressing micron-scale aluminum core-shell particles to improve reactivity.
AB  - The main direction in increasing reactivity of aluminum (Al) particles for
      energetic applications is reduction in their size down to nanoscale. However, Al
      nanoparticles are 30-50 times more expensive than micron scale particles and
      possess safety and environmental issues. Here, we improved reactivity of Al
      micron scale particles by synthesizing pre-stressed core-shell structures. Al
      particles were annealed and quenched to induce compressive stresses in the
      alumina passivation shell surrounding Al core. This thermal treatment was
      designed based on predictions of the melt-dispersion mechanism (MDM); a theory
      describing Al particle reaction under high heating rate. For all anneal treatment
      temperatures, experimental flame propagation rates for Al combined with nanoscale
      copper oxide (CuO) are in quantitative agreement with the theoretical predictions
      based on the MDM. The best treatment increases flame rate by 36% and achieves 68%
      of that for the best Al nanoparticles. 

PMID- 25597746
TI  - Keyhole anterolateral thigh flap: A special way of partition for reconstruction
      around a protruding structure or cavity/tunnel.
AB  - BACKGROUND: Anterolateral thigh (ALT) flap is now a workhorse flap for
      reconstruction of skin and soft tissue defects. However, there are some drawbacks
      in its application, and revisions are often needed after surgery. Here, we
      present the results of the use of a special type of partition for ALT flap based
      on the concept of perforator flap vascular anatomy for reconstruction around a
      protruding structure, a cavity or a canal, in patients. PATIENTS AND METHODS: We
      used the keyhole design for reconstruction with ALT flaps in five patients.
      Wounds involved circumferential soft tissue defects around the following
      structures: thumb (two cases), penis, ear canal, and anus. Defects arose
      following excision of scar contracture, arterio-venous malformation, Paget's
      disease, squamous cell carcinoma, and Fournier's gangrene, respectively. The ALT
      flap was raised based on perforators. The flap was partitioned with a keyhole
      incision performed in a zone between two perforators or distal to them, avoiding
      complete split of the flap and minimizing disruption of its vascular crossover.
      The circulation of the flap was well preserved. The closure of the flap had no
      tension. RESULTS: All the flaps had 100% viability without partial loss. Mean
      follow-up was of 7.4 months (range 4 - 11 months). Significant functional
      improvement was achieved in the two thumb cases. Adequate patency of the ear and
      anal canals was obtained. No contracture around the penis was observed.
      CONCLUSION: The keyhole design may be a valuable method of partition of the ALT
      flap for specific reconstructions around protruding organs, cavities, or canals.

PMID- 25597748
TI  - Communicating with biobank participants: preferences for receiving and providing
      updates to researchers.
AB  - BACKGROUND: Research biobanks collect biologic samples and health information.
      Previous work shows that biobank participants desire general study updates, but
      preferences about the method or frequency of these communications have not been
      explored. Thus, we surveyed participants in a long-standing research biobank.
      METHODS: Eligible participants were drawn from a study of patients with
      personal/family history suggestive of Cowden syndrome, a poorly recognized
      inherited cancer syndrome. Participants gave blood samples and access to medical
      records and received individual results but had no other study interactions. The
      biobank had 3,618 participants at sampling. Survey eligibility included age >=18
      years, enrollment within the biobank's first 5 years, normal PTEN analysis, and
      contiguous U.S. address. Multivariate logistic regression analyses identified
      predictors of participant interest in Internet-based versus offline methods and
      methods allowing participant-researcher interaction versus one-way communication.
      Independent variables were narrowed by independent Pearson correlations by cutoff
      P < 0.2, with P < 0.02 considered significant. RESULTS: Surveys were returned
      from 840 of 1,267 (66%) eligible subjects. Most (97%) wanted study updates, with
      92% wanting updates at least once a year. Participants preferred paper (66%) or
      emailed (62%) newsletter methods, with 95% selecting one of these. Older, less
      educated, and lower-income respondents strongly preferred offline approaches (P <
      0.001). Most (93%) had no concerns about receiving updates and 97% were willing
      to provide health updates to researchers. CONCLUSION: Most participants were
      comfortable receiving and providing updated information. Demographic factors
      predicted communication preferences. IMPACT: Researchers should make plans for
      ongoing communication early in study development and funders should support the
      necessary infrastructure for these efforts.

PMID- 25597749
TI  - Serum YKL-40 in risk assessment for colorectal cancer: a prospective study of
      4,496 subjects at risk of colorectal cancer.
AB  - The aim of the present study was to test the hypothesis that high serum YKL-40
      associates with colorectal cancer in subjects at risk of colorectal cancer. We
      measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men,
      2,432 women, median age 61 years (range, 18-97)] referred to endoscopy due to
      symptoms or other risk factors for colorectal cancer. Blood samples were
      collected just before large bowel endoscopy. Serum YKL-40 was determined by
      ELISA. Serum YKL-40 was higher (P < 0.0001, unadjusted for confounding
      covariates) in subjects diagnosed with colon cancer (median 126 MUg/L, 25%-75%:
      80-206 MUg/L) and rectal cancer (104, 72-204 MUg/L) compared with subjects with
      adenoma (84, 53-154 MUg/L), other nonmalignant findings (79, 49-138 MUg/L), and
      no findings (62, 41-109 MUg/L). Serum YKL-40 independently predicted colorectal
      cancer [OR, 1.53; 95% confidence interval (CI), 1.40-1.67; AUC = 0.68, P <
      0.0001]. Restricting the analysis to subjects with no comorbidity increased the
      OR for serum YKL-40 to predict colorectal cancer (OR, 1.82; 1.58-2.08; AUC =
      0.73, P < 0.0001). Combining serum YKL-40 and CEA demonstrated that both were
      significant [(YKL-40, OR, 1.27; 95% CI, 1.16-1.40); (CEA, OR, 1.92; 1.75-2.10;
      AUC = 0.75, P < 0.0001; OR for a 2-fold difference in marker level)].
      Multivariable analysis (YKL-40, CEA, age, gender, body mass index, and center)
      showed that serum YKL-40 was a predictor for colorectal cancer in individuals
      without comorbidity (OR, 1.25; 95% CI, 1.05-1.40; P = 0.012), whereas this was
      not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P = 0.80).
      In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and
      without comorbidity associates with colorectal cancer. Determination of serum YKL
      40 may be useful in combination with other biomarkers in risk assessment for
      colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 621-6. (c)2015 AACR. 

PMID- 25597752
TI  - Mass spectrometric immunoassay raises doubt for the existence of parathyroid
      hormone fragment 7-84.

PMID- 25597751
TI  - Antihypertensive drugs for elderly patients: a cross- sectional study.
AB  - INTRODUCTION: As the population ages, the prevalence of hypertension also
      increases. Although primary care is usually the patient's first point of contact
      for healthcare, little is known about the management of hypertension among
      elderly patients at the primary care level. This study aimed to determine the
      antihypertensive prescription trend for elderly patients, the predictors of
      antihypertensive use and any inappropriate prescribing practices in both public
      and private primary care settings. METHODS: Data on patient demographics,
      diagnosis, prescription pattern, payment mode and follow-up was extracted from a
      cross-sectional study involving 122 public primary care clinics and 652 private
      primary care clinics in Malaysia. Encounters with hypertensive patients aged >=
      60 years were included. RESULTS: A total of 1,017 antihypertensive medications
      were prescribed - calcium channel blockers (27.1%), beta blockers (25.5%),
      diuretics (23.3%), angiotensin-converting enzyme inhibitors (14.9%) and
      angiotensin receptor blockers (6.3%). Out of the 614 patient encounters, 53.1% of
      the patients were prescribed monotherapy, 31.6% were prescribed dual therapy,
      12.2% triple therapy, 2.8% quadruple therapy and 0.3% quintuple therapy. Type of
      primary care clinic and payment mode were significant predictors for the
      prescription of combination therapy and fixed-dose combination therapy,
      respectively. Four types of inappropriate prescriptions were identified.
      CONCLUSION: Calcium channel blockers were the most common antihypertensive drug
      prescribed and more than half of the elderly patients were on monotherapy.
      Antihypertensive drug prescription was found to be associated with the type of
      primary care clinic and the payment mode, suggesting that prescription is
      influenced by the cost of the drug.

PMID- 25597750
TI  - The effects of the Trendelenburg position and the Valsalva manoeuvre on internal
      jugular vein diameter and placement in children.
AB  - INTRODUCTION: We compared the effects of various surgical positions, with and
      without the Valsalva manoeuvre, on the diameter of the right internal jugular
      vein (RIJV). METHODS: We recruited 100 American Society of Anesthesiologists
      physical status class I patients aged 2-12 years. The patients' heart rate, blood
      pressure, peripheral oxygen saturation and end-tidal CO2 pressure were monitored.
      Induction of anaesthesia was done using 1% propofol 10 mg/mL and fentanyl 2
      ug/kg, while maintenance was achieved with 2% sevoflurane in a mixture of 50/50
      oxygen and air (administered via a laryngeal mask airway). The RIJV diameter was
      measured using ultrasonography when the patient was in the supine position.
      Thereafter, it was measured when the patient was in the supine position +
      Valsalva, followed by the Trendelenburg, Trendelenburg + Valsalva, reverse
      Trendelenburg, and reverse Trendelenburg + Valsalva positions. A 15 degrees 
      depression or elevation was applied for the Trendelenburg position, and an airway
      pressure of 20 cmH2O was applied in the Valsalva manoeuvre. During
      ultrasonography, the patient's head was tilted 20 degrees  to the left. RESULTS:
      When compared to the mean RIJV diameter in the supine position, the mean RIJV
      diameter was significantly greater in all positions (p < 0.001) except for the
      reverse Trendelenburg position. The greatest increase in diameter was observed in
      the Trendelenburg position with the Valsalva manoeuvre (p < 0.001). CONCLUSION:
      In paediatric patients, the application of the Trendelenburg position with the
      Valsalva manoeuvre gave the greatest increase in RIJV diameter. The reverse
      Trendelenburg position had no significant effect on RIJV diameter.

PMID- 25597753
TI  - Technique advance to avoid hepatic venous outflow obstruction in pediatric living
      donor liver transplantation.
AB  - HVOO represents a serious critical complication of pediatric living-donor liver
      transplantation because open surgical repair is virtually impossible. Currently,
      despite several technical innovations and the introduction of triangulated
      anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is
      still considerable. The aim of this study was to propose a new technique for
      hepatic venous reconstruction that avoids the original orifice of the recipient
      hepatic veins. Instead, anastomosis is performed in a newly created wide
      longitudinal orifice in the anterior wall of the recipient inferior vena cava. A
      total of 210 living related-donor liver transplantations were performed using two
      methods for reconstruction of the hepatic vein. Group 1 included 69 patients
      subjected to direct anastomosis of the orifice of the graft hepatic vein and a
      wide orifice created in the recipient inferior vena cava by the confluence of the
      orifices of the right, left, and middle hepatic veins. Group 2 included 141
      patients in whom the original orifices of the recipient hepatic veins were
      closed, the inferior vena cava was widely opened, and a long longitudinal
      anastomosis was performed using two lines of continuous sutures. Diagnosis of
      HVOO was suspected based on clinical findings and ultrasound studies and then
      confirmed by liver biopsy and interventional radiology examinations. Among the 69
      recipients in group 1, 16 patients died due to graft problems during the
      postoperative period and eight of the survivors (15.1%) presented with HVOO. In
      group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A
      comparison of the incidence of HVOO between groups revealed a significant
      difference (p = 0.01). Hepatic venous reconstruction during pediatric living
      donor liver transplantation should be performed using a wide longitudinal
      incision in the anterior wall of the recipient inferior vena cava because this
      technique eliminated anastomosis complications. 

PMID- 25597755
TI  - Response to: Does the Nerium oleander extract PBI-05204 have potential for
      pancreatic cancer?

PMID- 25597756
TI  - Variation in foliar respiration and wood CO2 efflux rates among species and
      canopy layers in a wet tropical forest.
AB  - As tropical forests respond to environmental change, autotrophic respiration may
      consume a greater proportion of carbon fixed in photosynthesis at the expense of
      growth, potentially turning the forests into a carbon source. Predicting such a
      response requires that we measure and place autotrophic respiration in a complete
      carbon budget, but extrapolating measurements of autotrophic respiration from
      chambers to ecosystem remains a challenge. High plant species diversity and
      complex canopy structure may cause respiration rates to vary and measurements
      that do not account for this complexity may introduce bias in extrapolation more
      detrimental than uncertainty. Using experimental plantations of four native tree
      species with two canopy layers, we examined whether species and canopy layers
      vary in foliar respiration and wood CO2 efflux and whether the variation relates
      to commonly used scalars of mass, nitrogen (N), photosynthetic capacity and wood
      size. Foliar respiration rate varied threefold between canopy layers, ~0.74 MUmol
      m(-2) s(-1) in the overstory and ~0.25 MUmol m(-2) s(-1) in the understory, but
      little among species. Leaf mass per area, N and photosynthetic capacity explained
      some of the variation, but height explained more. Chamber measurements of foliar
      respiration thus can be extrapolated to the canopy with rates and leaf area
      specific to each canopy layer or height class. If area-based rates are sampled
      across canopy layers, the area-based rate may be regressed against leaf mass per
      area to derive the slope (per mass rate) to extrapolate to the canopy using the
      total leaf mass. Wood CO2 efflux varied 1.0-1.6 MUmol m(-2) s(-1) for overstory
      trees and 0.6-0.9 MUmol m(-2) s(-1) for understory species. The variation in wood
      CO2 efflux rate was mostly related to wood size, and little to species, canopy
      layer or height. Mean wood CO2 efflux rate per surface area, derived by
      regressing CO2 efflux per mass against the ratio of surface area to mass, can be
      extrapolated to the stand using total wood surface area. The temperature response
      of foliar respiration was similar for three of the four species, and wood CO2
      efflux was similar between wet and dry seasons. For these species and this
      forest, vertical sampling may yield more accurate estimates than would temporal
      sampling. 

PMID- 25597754
TI  - The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug
      resistance protein ABCB1 but does not inhibit transport function at
      pharmacologically relevant concentrations.
AB  - Background Crenolanib (crenolanib besylate, 4-piperidinamine, 1-[2-[5-[(3-methyl
      3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-, monobenzenesulfonate)
      is a potent and specific type I inhibitor of fms-like tyrosine kinase 3 (FLT3)
      that targets the active kinase conformation and is effective against FLT3 with
      internal tandem duplication (ITD) with point mutations induced by, and conferring
      resistance to, type II FLT3 inhibitors in acute myeloid leukemia (AML) cells.
      Crenolanib is also an inhibitor of platelet-derived growth factor receptor alpha
      and beta and is in clinical trials in both gastrointestinal stromal tumors and
      gliomas. Methods We tested crenolanib interactions with the multidrug resistance
      associated ATP-binding cassette proteins ABCB1 (P-glycoprotein), ABCG2 (breast
      cancer resistance protein) and ABCC1 (multidrug resistance-associated protein 1),
      which are expressed on AML cells and other cancer cells and are important
      components of the blood-brain barrier. Results We found that crenolanib is a
      substrate of ABCB1, as evidenced by approximate five-fold resistance of ABCB1
      overexpressing cells to crenolanib, reversal of this resistance by the ABCB1
      specific inhibitor PSC-833 and stimulation of ABCB1 ATPase activity by
      crenolanib. In contrast, crenolanib was not a substrate of ABCG2 or ABCC1.
      Additionally, it did not inhibit substrate transport by ABCB1, ABCG2 or ABCC1, at
      pharmacologically relevant concentrations. Finally, incubation of the FLT3-ITD
      AML cell lines MV4-11 and MOLM-14 with crenolanib at a pharmacologically relevant
      concentration of 500 nM did not induce upregulation of ABCB1 cell surface
      expression. Conclusions Thus ABCB1 expression confers resistance to crenolanib
      and likely limits crenolanib penetration of the central nervous system, but
      crenolanib at therapeutic concentrations should not alter cellular exposure to
      ABC protein substrate chemotherapy drugs. 

PMID- 25597757
TI  - Interleukin-13 promotes expression of Alix to compromise renal tubular epithelial
      barrier function.
AB  - The epithelial barrier dysfunction plays a critical role in a number of kidney
      diseases. The mechanism is unclear. Alix is a protein involving in protein
      degradation in epithelial cells. This study aims to investigate that interleukin
      (IL)-13 inhibits Alix to compromise the kidney epithelial barrier function. In
      this study, the murine collecting duct cell line (M-1) was cultured in Transwell
      inserts to investigate the significance of Alix in compromising the epithelial
      barrier functions. T cell (Teff cells) proliferation assay was employed to assess
      the antigenicity of ovalbumin (OVA) that was transported across the M-1 monolayer
      barrier. The results showed that M-1 cells express Alix. Exposure to interleukin
      (IL)-13 markedly decreased the expression of Alix in M-1 cells, which compromised
      the M-1 monolayer barrier functions by showing the increases in the permeability
      to OVA. Over-expression of Alix abolished the IL-13-induced M-1 monolayer barrier
      dysfunction. Knockdown of Alix significantly increased M-1 monolayer
      permeability. The OVA collected from the Transwell basal chambers induced the OVA
      specific T cell proliferation. We conclude that IL-13 compromises M-1 epithelial
      barrier functions via inhibiting Alix expression. 

PMID- 25597758
TI  - Companion diagnostics: the key to personalized medicine. Foreword.
AB  - This special focus issue of Expert Review of Molecular Diagnostics on in vitro
      companion diagnostics aims to provide the reader with up-to-date knowledge on
      this fast-evolving area of medical research. Companion diagnostics takes up a
      central role in the development of targeted drugs and to a large extent, the
      success of this type of therapy depends on their performance. Companion
      diagnostic assays have a single patient as a point of reference and they will be
      decisive for the move toward a more precise and individualized pharmacotherapy.
      The 'first generation' of companion diagnostic assays relies on single biomarker
      detection but with our increasing understanding of disease pathophysiology a new
      generation of assays is under development, which will be based on patient
      profiling and multiplex platforms. 

PMID- 25597759
TI  - Physiological responses to simulated firefighter exercise protocols in varying
      environments.
AB  - For decades, research to quantify the effects of firefighting activities and
      personal protective equipment on physiology and biomechanics has been conducted
      in a variety of testing environments. It is unknown if these different
      environments provide similar information and comparable responses. A novel
      Firefighting Activities Station, which simulates four common fireground tasks, is
      presented for use with an environmental chamber in a controlled laboratory
      setting. Nineteen firefighters completed three different exercise protocols
      following common research practices. Simulated firefighting activities conducted
      in an environmental chamber or live-fire structures elicited similar
      physiological responses (max heart rate: 190.1 vs 188.0 bpm, core temperature
      response: 0.047 degrees C/min vs 0.043 degrees C/min) and accelerometry counts.
      However, the response to a treadmill protocol commonly used in laboratory
      settings resulted in significantly lower heart rate (178.4 vs 188.0 bpm), core
      temperature response (0.037 degrees C/min vs 0.043 degrees C/min) and physical
      activity counts compared with firefighting activities in the burn building.
      Practitioner Summary: We introduce a new approach for simulating realistic
      firefighting activities in a controlled laboratory environment for ergonomics
      assessment of fire service equipment and personnel. Physiological responses to
      this proposed protocol more closely replicate those from live-fire activities
      than a traditional treadmill protocol and are simple to replicate and
      standardise. 

PMID- 25597760
TI  - Assessment of aged mdx mice by electrical impedance myography and magnetic
      resonance imaging.
AB  - INTRODUCTION: Similar to magnetic resonance imaging (MRI), electrical impedance
      myography (EIM) is dependent on the presence and location of water in muscle to
      assess neuromuscular diseases. We compared the 2 technologies in mdx mice to
      better understand their relationship. METHODS: EIM and MRI, using T2 relaxation
      and diffusion-weighted imaging (DWI), were performed on the gastrocnemius of 10
      mdx and 10 wild-type mice. Muscle function and tissue composition measurements
      were compared with the EIM and MRI data. RESULTS: EIM reactance and T2 relaxation
      mapping can discriminate healthy from diseased mice (P <  .001 for both), but DWI
      could not. Both T2 relaxation and EIM reactance also correlated closely with
      muscle function/composition and with each other. CONCLUSION: Given the low cost
      of EIM and the simplicity of application, it may be a valuable alternative to
      muscle MRI in Duchenne muscular dystrophy, where simple cumulative indices of
      muscle health are being sought.

PMID- 25597761
TI  - Pediatric reference intervals for plasma free and total metanephrines established
      with a parametric approach: relevance to the diagnosis of neuroblastoma.
AB  - BACKGROUND: Urine catecholamines, vanillylmandelic, and homovanillic acid are
      recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma
      free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and
      methoxytyramine (MT) could represent a convenient alternative to those urine
      markers. The primary objective of this study was to establish pediatric centile
      charts for plasma metanephrines. Secondarily, we explored their diagnostic
      performance in 10 patients with neuroblastoma. PROCEDURE: We recruited 191
      children (69 females) free of neuroendocrine disease to establish reference
      intervals for plasma metanephrines, reported as centile curves for a given age
      and sex based on a parametric method using fractional polynomials models. Urine
      markers and plasma metanephrines were measured in 10 children with neuroblastoma
      at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric
      detection and plasma free metanephrines by tandem LC-MS. RESULTS: We observed a
      significant age-dependence for tNMN, fNMN, and fMN, and a gender and age
      dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of
      quantification in 94% of the children. All patients with neuroblastoma at
      diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas
      their fMN and tMN were mostly within the normal range. As expected, urine assays
      were inconstantly predictive of the disease. CONCLUSIONS: A continuous model
      incorporating all data for a given analyte represents an appealing alternative to
      arbitrary partitioning of reference intervals across age categories. Plasma
      metanephrines are promising biomarkers for neuroblastoma, and their performances
      need to be confirmed in a prospective study on a large cohort of patients.

PMID- 25597762
TI  - Aptamer-mediated up-conversion core/MOF shell nanocomposites for targeted drug
      delivery and cell imaging.
AB  - Multifunctional nanocarriers for targeted bioimaging and drug delivery have
      attracted much attention in early diagnosis and therapy of cancer. In this work,
      we develop a novel aptamer-guided nanocarrier based on the mesoporous metal
      organic framework (MOF) shell and up-conversion luminescent NaYF4:Yb(3+)/Er(3+)
      nanoparticles (UCNPs) core for the first time to achieve these goals. These
      UCNPs, chosen as optical labels in biological assays and medical imaging, could
      emit strong green emission under 980 nm laser. The MOF structure based on iron
      (III) carboxylate materials [MIL-100 (Fe)] possesses high porosity and non
      toxicity, which is of great value as nanocarriers for drug storage/delivery. As a
      unique nanoplatform, the hybrid inorganic-organic drug delivery vehicles show
      great promising for simultaneous targeted labeling and therapy of cancer cells.

PMID- 25597764
TI  - Survey on the use of health consultation services provided in a Japanese urban
      public housing area with a high elderly population.
AB  - OBJECTIVE: The aim of the present study was to determine how the elderly in an
      urban public housing area intends to utilize health consultation services.
      METHODS: In December 2011, a cross-sectional posting survey was carried out on
      2000 randomly selected elderly residents in an urban public housing area in
      Japan. The survey included information on the intention of use of health
      consultation services provided in the community, demographic background, living
      situation, medical and social care situation, and the concerns and desires about
      the services. RESULTS: We received 553 responses from the survey. Of the 534
      responders who had never used the service, 150 (28.1%) intended to use, 313
      (58.6%) were undecided and 71 (13.3%) expressed having no intention to use.
      Binominal logistic regression analysis showed that individuals who intended to
      use it tended to have the following features: aged >=70 years (OR 2.35, 95% CI
      1.41-3.93), resident of the complex for <10 years (OR 1.94, 95% CI 1.15-3.27),
      low sense of well-being (OR 3.69, 95% CI 1.03-13.26), family-related stress (OR
      1.72, 95% CI 1.01-2.93), outpatient of internal medicine (OR 1.74, 95% CI 1.10
      2.75), outpatient of cancer treatment (OR 2.58, 95% CI 1.15-5.77), history of
      unpleasant medical experience (OR 1.68, 95% CI 1.03-2.73), desire for a free
      health consultation (OR 1.80, 95% CI 1.07-3.04), desiring to consult about
      diseases (OR 2.01, 95% CI 1.27-3.18) and desiring to consult about caregiving (OR
      1.64, 95% CI 1.05-2.56). CONCLUSION: Approximately 30% of residents had the
      intention of using the health consultation services provided in the community.
      The people who were more likely to use the services tended to have more intensive
      consultation support.

PMID- 25597763
TI  - Changes in the metabolism of sphingolipids after subarachnoid hemorrhage.
AB  - We previously described how ceramide (Cer), a mediator of cell death, increases
      in the cerebrospinal fluid (CSF) of subarachnoid hemorrhage (SAH) patients. This
      study investigates the alterations of biochemical pathways involved in Cer
      homeostasis in SAH. Cer, dihydroceramide (DHC), sphingosine-1-phosphate (S1P),
      and the activities of acid sphingomyelinase (ASMase), neutral sphingomyelinase
      (NSMase), sphingomyelinase synthase (SMS), S1P-lyase, and glucosylceramide
      synthase (GCS) were determined in the CSF of SAH subjects and in brain homogenate
      of SAH rats. Compared with controls (n = 8), SAH patients (n = 26) had higher
      ASMase activity (10.0 +/- 3.5 IF/ul. min vs. 15.0 +/- 4.6 IF/ul * min; P = 0.009)
      and elevated levels of Cer (11.4 +/- 8.8 pmol/ml vs. 33.3 +/- 48.3 pmol/ml; P =
      0.001) and DHC (1.3 +/- 1.1 pmol/ml vs. 3.8 +/- 3.4 pmol/ml; P = 0.001) in the
      CSF. The activities of GCS, NSMase, and SMS in the CSF were undetectable. Brain
      homogenates from SAH animals had increased ASMase activity (control: 9.7 +/- 1.2
      IF/ug * min; SAH: 16.8 +/- 1.6 IF/ug * min; P < 0.05) and Cer levels (control:
      3,422 +/- 26 fmol/nmol of total lipid P; SAH: 7,073 +/- 2,467 fmol/nmol of total
      lipid P; P < 0.05) compared with controls. In addition, SAH was associated with a
      reduction of 60% in S1P levels, a 40% increase in S1P-lyase activity, and a
      twofold increase in the activity of GCS. In comparison, NSMase and SMS activities
      were similar to controls and SMS activities similar to controls. In conclusion,
      our results show an activation of ASMase, S1P-lyase, and GCS resulting in a shift
      in the production of protective (S1P) in favor of deleterious (Cer) sphingolipids
      after SAH. Additional studies are needed to determine the effect of modulators of
      the pathways described here in SAH.

PMID- 25597765
TI  - Syndromic intellectual disability: a new phenotype caused by an aromatic amino
      acid decarboxylase gene (DDC) variant.
AB  - The causative variant in a consanguineous family in which the three patients (two
      siblings and a cousin) presented with intellectual disability, Marfanoid habitus,
      craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has
      been identified through whole exome sequencing (WES) analysis. WES study
      identified a homozygous DDC variant in the patients, c.1123C>T, resulting in
      p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic
      disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643)
      characterized by hypotonia, oculogyric crises, excessive sweating, temperature
      instability, dystonia, severe neurologic dysfunction in infancy, and specific
      abnormalities of neurotransmitters and their metabolites in the cerebrospinal
      fluid (CSF). In our family, analysis of neurotransmitters and their metabolites
      in patient's CSF shows a pattern compatible with AADC deficiency, although the
      clinical signs are different from the classic form. Our work expands the
      phenotypic spectrum associated with DDC variants, which therefore can cause an
      additional novel syndrome without typical movement abnormalities. 

PMID- 25597766
TI  - The intergenic-junction variant (genotype 2 isolate) of hepatitis E virus
      restores the CREX 'stem-loop' structural integrity, essential for viral life
      cycle.
AB  - Among the known human HEV strains (genotypes 1, 2, 3 and 4), the genotype 2
      Mexican isolate has two 'double-base' substitutions (5'U5100G5101
      >CU/3'C5117U5118->GG) flanking the conserved cis-reactive element (CRE) in the
      intergenic-junction sequences. While the 'C5100U5101' natural mutations in the
      upstream ORF1 coding region replace 'alanine' for the conserved 'valine', the
      'G5117G5118' doublet resides in the downstream non-coding/promoter region of ORF3
      gene. Though a stable 'stem-loop' structure containing CRE, critical for virus
      replication had been reported, the phenotypic effect of genotype 2 'CU/GG'
      variations were neither mentioned nor explored. In this study, the evolutionary
      significance of such tolerable mutations in the conserved regulatory-sequences
      was investigated. Multiple sequence alignment of intergenic-junction of human HEV
      strains showed further base conservations flanking the CRE sequences. In silico
      analysis of the conserved sequences (nts. 5099-5121) of the representative
      genotypes revealed a stable RNA 'stem-loop' structure (CREX). Of the four
      genotype-specific CREX, the Mexican mutant bases 'CU/GG' very interestingly,
      compensated and complemented themselves (5'C5100:3'G5118 and 5'U5101:3'G5117) in
      the 'lower-stem'. The substitution of 'GG' bases in the ORF3 promoter-region did
      not affect its 'optimal-context' and therefore, negated its regulatory role at
      'nucleotide' level. Virtual mutations introduced to break the two base-pairings
      in the CREX 'lower-stem', completely destabilized the secondary structure.
      Further molecular characterization of the CREX mutants in HEV-SAR55 replicon
      background showed a drastic downregulation of viral RNA replication in S10-3
      cells. Though the CREX-mutant RNA were encapsidated into trans-complemented viral
      capsids (ORF2), and produced virions, they were poorly infectious to naive
      HepG2/C3A cells. In conclusion, the compensatory mutations in the intergenic
      junction of Mexican isolate suggest strict conservation of the CREX 'stem-loop'
      structure, essential for HEV genome replication. This could have a greater
      regulatory role in viral life cycle, including RNA packaging.

PMID- 25597767
TI  - Gene set by de novo assembly of Perilla species and expression profiling between
      P. frutescens (L.) var. frutescens and var. crispa.
AB  - Perilla frutescens (L.) Britt. is a self-pollinating annual species and is widely
      cultivated in China, Korea and Japan as an economic crop and a source of medicine
      and spices. In this study, we sequenced one cultivar variety (PF98095) of P.
      frutescens (L.) var. frutescens Britt., which was assembled as reference and
      other three varieties (PF11109, weedy of var. frutescens, PF06336 and PF06353,
      cultivars of varieties crispa) in order to carry out comparative expression
      profiling within cultivar and weedy in varieties frutescens and between varieties
      frutescens and varieties crispa of cultivar type in P. frutescens. Assembly of
      PF98095, annotation mapping, DEG (differentially expressed gene) profiling, and
      comparative analysis were performed. We found that more than 65% of the reads
      were mapped to the reference of P. frutescens gene set. Moreover, we detected
      22,962 DEGs in the weedy variety compared to the cultivar, and also, 22,138 and
      23,845 DEGs were identified in two cultivars according to the reference,
      respectively. The DEGs and functional classification were developed to analyze
      the differences between weedy and cultivar and between varieties frutescens and
      varieties crispa of Perilla. Furthermore, candidate genes for the different color
      and seed size of Perilla were identified that could be further investigated in
      future study. The herein results may play a significant role, and contribute in
      functional transcriptome studies of Perilla.

PMID- 25597768
TI  - Effectiveness of tissue harmonic echo imaging and contrast-enhanced endoscopic
      ultrasound for diagnosing mural nodules of intraductal papillary mucinous
      neoplasms.

PMID- 25597769
TI  - An innovative anion regulation strategy for energy bands of semiconductors: a
      case from Bi2O3 to Bi2O(OH)2SO4.
AB  - How to develop a new, efficient photo catalyst is still a big challenge to us. A
      suitable band gap is the key for light absorption of semiconductor. Herein, an
      innovative anion intercalation strategy is, for the first time, developed to
      regulate the energy band of semiconductor. Typically, we introduce a layered
      sulfate compound (Bi2O(OH)2SO4) as a new photo catalyst, which has not been known
      before. Both partial density of states (PDOS) and total density of states (TDOS)
      have demonstrated that compared with Bi2O3 (2.85 eV), the band gap of
      Bi2O(OH)2SO4 has been widened to 4.18 eV by the intercalation of sulfate anion.
      Moreover, the band gap width of oxyacid salt compound is mainly predominated by
      the number of the outmost electrons (NOE) of central atom of anion. This study
      suggests that new photo catalysts can be developed by grouping anions with the
      existing oxides or sulfides.

PMID- 25597771
TI  - Highlights from the latest research in nanomedicine.

PMID- 25597770
TI  - Nanomedicine for targeted photothermal cancer therapy: where are we now?

PMID- 25597773
TI  - Advances in studies of nanoparticle-biomembrane interactions.
AB  - Nanoparticles (NPs) are widely applied in nanomedicine and diagnostics based on
      the interactions between NPs and the basic barrier (biomembrane). Understanding
      the underlying mechanism of these interactions is important for enhancing their
      beneficial effects and avoiding potential nanotoxicity. Experimental,
      mathematical and numerical modeling techniques are involved in this field. This
      article reviews the state-of-the-art techniques in studies of NP-biomembrane
      interactions with a focus on each technology's advantages and disadvantages. The
      aim is to better understand the mechanism of NP-biomembrane interactions and
      provide significant guidance for various fields, such as nanomedicine and
      diagnosis. 

PMID- 25597772
TI  - Micro-/nano-structured superhydrophobic surfaces in the biomedical field: part I:
      basic concepts and biomimetic approaches.
AB  - Inspired by natural structures, great attention has been devoted to the study and
      development of surfaces with extreme wettable properties. The meticulous study of
      natural systems revealed that the micro/nano-topography of the surface is
      critical to obtaining unique wettability features, including superhydrophobicity.
      However, the surface chemistry also has an important role in such surface
      characteristics. As the interaction of biomaterials with the biological milieu
      occurs at the surface of the materials, it is expected that synthetic substrates
      with extreme and controllable wettability ranging from superhydrophilic to
      superhydrophobic regimes could bring about the possibility of new investigations
      of cell-material interactions on nonconventional surfaces and the development of
      alternative devices with biomedical utility. This first part of the review will
      describe in detail how proteins and cells interact with micro/nano-structured
      surfaces exhibiting extreme wettabilities. 

PMID- 25597774
TI  - Delivery of therapeutics using nanocarriers for targeting cancer cells and cancer
      stem cells.
AB  - Development of cancer resistance, cancer relapse and metastasis are attributed to
      the presence of cancer stem cells (CSCs). Eradication of this subpopulation has
      been shown to increase life expectancy of patients. Since the discovery of CSCs a
      decade ago, several strategies have been devised to specifically target them but
      with limited success. Nanocarriers have recently been employed to deliver anti
      CSC therapeutics for reducing the population of CSCs at the tumor site with great
      success. This review discusses the different therapeutic strategies that have
      been employed using nanocarriers, their advantages, success in targeting CSCs and
      the challenges that are to be overcome. Exploiting this new modality of cancer
      treatment in the coming decade may improve outcomes profoundly with promise of
      effective treatment response and reducing relapse and metastasis. 

PMID- 25597775
TI  - Nanobody-based cancer therapy of solid tumors.
AB  - The development of tumor-targeted therapies using monoclonal antibodies has been
      successful during the last 30 years. Nevertheless, the efficacy of antibody-based
      therapy is still limited and further improvements are eagerly awaited. One of the
      promising novel developments that may overcome the drawbacks of monoclonal
      antibody-based therapies is the employment of nanobodies. Current nanobody-based
      therapeutics can be divided into three different platforms with nanobodies
      functioning as: receptor antagonists; targeting moieties of effector domains; or
      targeting molecules on the surface of nanoparticles. In this article, we describe
      factors that affect their performance at three different stages: their systemic
      circulation upon intravenous injection; their extravasation and tumor
      penetration; and, finally, their interaction with target molecules. 

PMID- 25597776
TI  - A novel urodynamic model for lower urinary tract assessment in awake rats.
AB  - OBJECTIVES: To develop a urodynamic model incorporating external urethral
      sphincter (EUS) electromyography (EMG) in awake rats. MATERIALS AND METHODS:
      Bladder catheters and EUS EMG electrodes were implanted in female Sprague Dawley
      rats. Assessments were performed in awake, lightly restrained rats on
      postoperative day 12-14. Measurements were repeated in the same rat on day 16
      under urethane anaesthesia. Urodynamics and EUS EMG were performed
      simultaneously. In addition, serum creatinine and bladder histology was assessed.
      RESULTS: No significant differences in urodynamic parameters were found between
      bladder catheter only vs bladder catheter and EUS EMG electrode groups. Urethane
      anaesthesia evoked prominent changes in both urodynamic parameters and EUS EMG.
      Serum creatinine was within the normal limits in all rats. Bladder weight and
      bladder wall thickness were significantly increased in both the bladder catheter
      only and the bladder catheter and EUS EMG group compared with controls.
      CONCLUSIONS: Our novel urodynamic model allows repetitive measurements of both
      bladder and EUS function at different time points in the same rat under fully
      awake conditions and opens promising avenues to investigate lower urinary tract
      dysfunction in a translational approach.

PMID- 25597777
TI  - Exploring the Role of Mental Imagery in the Experience of Self-injury: An
      Interpretative Phenomenological Analysis.
AB  - BACKGROUND: Research has implicated causal, mediating and meaningful roles for
      mental imagery in the experience of psychological distress, including self
      injury. AIMS: The present study aimed to further the understanding of this
      relationship through exploring the lived experiences of mental imagery from the
      perspective of those who self-injure. METHOD: This study employed an inductive
      qualitative design using semi-structured interviews and Interpretative
      Phenomenological Analysis (IPA). Ten participants were recruited from
      universities in North West England. RESULTS: Three main themes were identified
      from the analysis: (i) The origins and precipitants of self-injurious imagery;
      (ii) What it is like to experience self-injurious imagery; and (iii) The meaning
      and interpretation of self-injurious imagery. CONCLUSIONS: The study findings
      indicate that mental imagery is an important experience for those who self
      injure. Clinical and research implications of the findings are discussed.

PMID- 25597780
TI  - A multi-journal partnership to highlight joint first-authors of manuscripts.

PMID- 25597779
TI  - Quantification of anthocyanins in elderberry and chokeberry dietary supplements.
AB  - Elderberry and chokeberry food supplements may be 'functional food' in patients
      with metabolic syndrome or influenza but, for this, adequate amounts of co-active
      ingredients must be consumed in the daily dose. This study aimed to quantify the
      anthocyanin content in three elderberry and six chokeberry products to assess
      their usefulness as functional food. Analyses were carried out using an
      established HPLC procedure. The minimum anthocyanin doses for the treatment of
      metabolic syndrome disorders were estimated as 110 mg per day and 3.5 g per day
      for influenza. Three products were inappropriate for clinical use. The lowest
      liquid supplies were achieved with a proprietary elderberry concentrate (11 mL)
      and a proprietary chokeberry mother juice (100 mL). Clinical studies are now
      required to prove the effectiveness and adapt the doses according to the clinical
      symptoms.

PMID- 25597778
TI  - Effect of active immunization against GnRH-I on the reproductive function in cat.
AB  - This study was designed to explore the effect of active immunization against
      maltose binding protein-gonadotropin releasing hormone I hexamer (MBP-GnRH-I6) on
      the reproductive function in cats. Each immunized cat was administered twice
      intramuscularly in the neck at 16 and 20 weeks old. The concentrations of the
      testosterone and estradiol and the level of anti-GnRH-I antibody in the serum
      were measured by radioimmunoassay and ELISA, respectively. The results showed
      that the weight and size of testicles and ovaries, and the concentrations of
      serum testosterone and estradiol in the immunized animals were lower than those
      of the control cats (P < 0.05), but that the levels of anti-GnRH-I antibody were
      significant higher compared to control animals (P < 0.05). Testicular tissues
      from the immunized male cats showed that seminiferous tubules were depauperate
      with the lumen relatively empty and that the differentiation of spermatogonia was
      not obvious. Tissues from the immunized female cats showed that the ovaries had
      many primordial follicles and primary follicles, but no secondary follicle was
      observed. These results showed active immunization against MBP-GnRH-I6 could make
      the gonads atrophy and reduce the concentrations of gonadal hormones, which
      suggested that MBP-GnRH-I6 was a very effective immunogen in the cat. 

PMID- 25597781
TI  - Rhodium-catalysed direct C-H allylation of N-sulfonyl ketimines with allyl
      carbonates.
AB  - A rhodium-catalysed direct C-H allylation of readily accessible N-sulfonyl
      ketimines with various allyl carbonates has successfully been achieved. The
      computational studies indicated that olefin insertion and beta-oxygen elimination
      steps were involved in the catalytic cycle. 

PMID- 25597782
TI  - Sumatriptan succinate sublingual fast dissolving thin films: formulation and in
      vitro/in vivo evaluation.
AB  - Sumatriptan succinate (SS) is a 5-HT1 receptor agonist used in the treatment of
      migraine having poor bioavailability (15%) due to its extensive first-pass
      effect. The aim of this work was to prepare SS sublingual fast dissolving thin
      films (SFDTFs) allowing the drug to directly enter the systemic circulation and
      bypassing the first-pass metabolism. Plain thin films were prepared using solvent
      casting technique adopting 2(3) * 3 factorial design to study the effect of
      polymer and plasticizer type and concentration on mechanical properties and in
      vitro disintegration time of the plain prepared films using Design-Expert(r).
      Medicated films were prepared after addition of 35 mg SS to each of the two
      selected plain formulae (F6 and F7) having desirability values above 0.9 showing
      the values of: 0.038, 0.039 kgf/mm(2) and 156.24, 164.16% and 0.0248, 0.0240
      kgf/mm(2) as tensile strength, percent elongation and elastic modulus,
      respectively. PVP K30 was efficient as crystallization inhibitor in retarding SS
      crystallization. Pharmacokinetic study of the optimum formula F7 (PVP K30:SS (1:1
      w/w)) in healthy human volunteers using LC/MS/MS revealed a shorter tmax (0.25 h)
      compared to Imitrex(r) tablet 25 mg (2 h) which is considered promising
      especially for the rapid relief of acute migraine attacks.

PMID- 25597783
TI  - HBME-1 and CD15 immunocytochemistry in the follicular variant of thyroid
      papillary carcinoma.
AB  - Papillary carcinoma is the most common thyroid malignancy. As the cytological
      diagnosis of papillary carcinoma is not difficult in patients with the usual type
      of lesion, fine-needle aspiration (FNA) cytology is an effective method for
      preoperative evaluation. However, this modality is often ineffective in
      identifying the follicular variant of papillary thyroid carcinoma (FVPTC) due to
      its similarity to other follicular lesions and the incompleteness of typical
      nuclear features. Therefore, we investigated the expression of immunocytochemical
      markers of papillary carcinoma in cytological specimens of FVPTC and evaluated
      their utilities. The immunoreactivity of HBME-1 and CD15 was investigated using
      50 imprint smear cytological specimens obtained from thyroid lesions, including
      13 FVPTC. The sensitivity and specificity of HBME-1 for FVPTC were 92% and 89%,
      respectively, while those of CD15 were 23% and 100%, respectively. In conclusion,
      HBME-1 is a sensitive marker of papillary carcinoma, including both usual type
      and FVPTC, in cytological specimens. Therefore, using HBME-1 immunocytochemistry
      in FNA cytology will lead to reduction of the incidence of false-negative
      diagnoses of FVPTC. Although CD15 is apparently inferior in terms of sensitivity
      for FVPTC, its excellent specificity will support the definitive diagnosis of
      thyroid malignancies, including FVPTC, after screening with HBME-1. 

PMID- 25597786
TI  - The redox-active nanomaterial toolbox for cancer therapy.
AB  - Advances in nanomaterials science contributed in recent years to develop new
      devices and systems in the micro and nanoscale for improving the diagnosis and
      treatment of cancer. Substantial evidences associate cancer cells and tumor
      microenvironment with reactive oxygen species (ROS), while conventional cancer
      treatments and particularly radiotherapy, are often mediated by ROS increase.
      However, the poor selectivity and the toxicity of these therapies encourage
      researchers to focus efforts in order to enhance delivery and to decrease side
      effects. Thus, the development of redox-active nanomaterials is an interesting
      approach to improve selectivity and outcome of cancer treatments. Herein, we
      describe an overview of recent advances in redox nanomaterials in the context of
      current and emerging strategies for cancer therapy based on ROS modulation. 

PMID- 25597785
TI  - Endostar attenuates melanoma tumor growth via its interruption of b-FGF mediated
      angiogenesis.
AB  - To develop optimal therapeutics is one of the hotspots in both clinical and basic
      melanoma studies. Previous studies indicate that fibroblast growth factors (b
      FGF/FGF-2), an angiogenesis inducer beyond VEGF, might be a potential drug target
      in melanoma. As a novel anti-angiogenesis peptide drug, Endostar has shown
      promising therapeutic efficacy in non-small cell lung cancer. However, the effect
      of Endostar on b-FGF-induced angiogenesis in melanoma is unraveled. To this end,
      both in vivo and in vitro experiments were conducted and it was found that
      treatment of Endostar could inhibit tumor growth, which was accompanied by
      decreased micro-vessel density and serum b-FGF levels in a mouse melanoma model.
      In addition, treatment with Endostar in blood vessel endothelial cells could
      reduce their proliferation, cell migration and tube formation capacity in a
      dosage-dependent manner. Moreover, treatment of Endostar could also attenuate b
      FGF-activated phosphorylation of p38 and ERK1/2 in HUVECs. These findings
      indicate that Endostar might exert its anti-tumor effect via suppressing b-FGF
      induced angiogenesis and b-FGF-activated MAPK signaling pathway, suggesting that
      Endostar might be a potential choice for clinical melanoma treatment. 

PMID- 25597787
TI  - Efficacy of homecare regimens for mechanical plaque removal in managing
      gingivitis a meta review.
AB  - FOCUSED QUESTION: Based on evidence as presented in systematic reviews what is
      the efficacy and safety of available homecare toothbrush regimens for mechanical
      plaque removal on plaque and gingivitis in adults? MATERIAL & METHODS: Three
      Internet sources were used (up to and including August 2014) to search for
      appropriate papers that satisfied the study purpose. Plaque scores and gingivitis
      scores were considered to be the primary parameter of interest. Safety was
      considered an important facet in relation to efficacy. Data and conclusions as
      presented in the selected papers were extracted. The potential risk of bias was
      estimated and the emerging evidence was graded. RESULTS: Independent screening of
      176 unique reviews resulted in 10 published and eligible systematic reviews. They
      were categorized into one review evaluating the effect of an oral hygiene
      instruction with a toothbrush on plaque and gingivitis scores, five evaluating
      the efficacy of manual and power toothbrushes and three reviews evaluating
      toothbrush safety and one evaluating toothbrush contamination. CONCLUSION: Tooth
      brushing is effective in reducing levels of dental plaque. With respect to
      gingivitis power toothbrushes have a benefit over manual toothbrushes. The
      greatest body of evidence was available for oscillating-rotating brushes. Tooth
      brushing generally can be considered safe for the teeth and their investing
      tissues.

PMID- 25597788
TI  - Estimation of in vivo dose of dermally applied chemicals leading to
      estrogen/androgen receptor-mediated toxicity from in vitro data--Illustration
      with four reproductive toxicants.
AB  - We present a quantitative in vitro-in vivo extrapolation framework enabling the
      estimation of the external dermal exposure dose from in vitro experimental data
      relevant to a toxicity pathway of interest. The framework adapts elements of the
      biological pathway altering dose (BPAD) method [Judson et al. Chem Res Toxicol
      2011;24:451] to the case of dermal exposure. Dermal doses of four toxicants
      equivalent to concentrations characterizing their effect on estrogen receptor
      alpha or androgen receptor activity in chemical-activated luciferase expression
      (CALUX) assays are estimated. The analysis shows that dermal BPADs, calculated
      from one in vitro concentration, can differ by up to a factor of 55, due to the
      impact applied dose and dermal exposure scenarios can have on skin permeation
      kinetics. These features should therefore be taken into account in risk
      assessment of dermally applied chemicals. 

PMID- 25597789
TI  - Determination of priority phenolic pollutants exploiting an in-syringe dispersive
      liquid-liquid microextraction-multisyringe chromatography system.
AB  - An automatic phenolic compounds analyzer is presented. The system performs online
      magnetic-stirring-assisted dispersive liquid-liquid microextraction before
      multisyringe chromatography (MSC) using a monolithic Chromolith Flash RP-18e
      column. The extraction behavior of the following phenolic pollutants: phenol, 2
      nitrophenol, 4-nitrophenol, 2-chlorophenol, 2,4-diclorophenol, and 2,4,6
      trichlorophenol, has been studied. A critical comparison of extractants (tributyl
      phosphate, acetonitrile, hexane, and 1-chlorobutane) and disperser solvents
      (acetone, acetonitrile, ethanol, methanol, 1-propanol, and 2-propanol) was made.
      Tributyl phosphate and acetonitrile were chosen as the extractant and the
      disperser solvent, respectively, since these showed the best performance. Phenols
      were online back-extracted into NaOH and neutralized before multi-isocratic
      chromatographic separation. The proposed analyzer can be applied for wide linear
      working ranges, i.e., between 40 and 20,000 MUg L(-1). The precision of the
      developed system has been proved, with maximum values for the intraday and
      interday precision of 4.4 % and 5.2 %, respectively, expressed as relative
      standard deviation, and high preconcentration factors (9.3-10.5) for most of the
      compounds studied. The method developed was successfully applied to natural water
      samples. 

PMID- 25597790
TI  - ABO-identical blood group matching has no survival benefit for AB heart
      transplant recipients.
AB  - BACKGROUND: Although identical blood group matching is preferred, it is uncertain
      if this results in improved survival and, if so, how large the survival benefits
      are. Earlier studies have yielded conflicting results and are mostly based on
      single-center cohorts with few long-term results. Recipients with blood group AB
      are of particular interest regarding nonidentical blood group matching because
      they may receive organs from all blood groups. We wanted to test the hypothesis
      that ABO-identical matching results in superior survival in recipients with blood
      group AB. METHODS: We used data from the International Society for Heart and Lung
      Transplantation registry to match a cohort of heart donors with transplant
      recipients with blood group AB. Cox regression analysis was used to assess the
      influence of blood group on outcome after heart transplantation. All-cause
      cumulative mortality during the study period was the primary end point. RESULTS:
      The study material consisted of 3,589 adult patients with blood group AB who had
      received heart transplants, representing 18,085 patient-years. No significant
      difference in survival after identical, as opposed to compatible, ABO matching
      was found for recipients with blood group AB. In subgroup analysis, we found
      improved survival for younger recipients (< 55 years) with blood group AB who
      underwent transplantation with organs from donor blood group O rather than AB (p
      = 0.02). CONCLUSIONS: We found no survival benefit for recipients with blood
      group AB transplanted with ABO-identical organs. In the subgroup of recipients
      younger than 55 years of age, our study suggests improved survival for recipients
      with blood group AB transplanted with an organ from a donor with blood group O.

PMID- 25597791
TI  - Studies on the molecular mechanisms of seed germination.
AB  - Seed germination that begins with imbibition and ends with radicle emergence is
      the first step for plant growth. Successful germination is not only crucial for
      seedling establishment but also important for crop yield. After being dispersed
      from mother plant, seed undergoes continuous desiccation in ecosystem and selects
      proper environment to trigger germination. Owing to the contribution of
      transcriptomic, proteomic, and molecular biological studies, molecular aspect of
      seed germination is elucidated well in Arabidopsis. Recently, more and more
      proteomic and genetic studies concerning cereal seed germination were performed
      on rice (Oryza sativa) and barley (Hordeum vulgare), which possess completely
      different seed structure and domestication background with Arabidopsis. In this
      review, both the common features and the distinct mechanisms of seed germination
      are compared among different plant species including Arabidopsis, rice, and
      maize. These features include morphological changes, cell and its related
      structure recovery, metabolic activation, hormone behavior, and transcription and
      translation activation. This review will provide more comprehensive insights into
      the molecular mechanisms of seed germination. 

PMID- 25597784
TI  - Targeting drivers of melanoma with synthetic small molecules and phytochemicals.
AB  - Melanoma is the least common form of skin cancer, but it is responsible for the
      majority of skin cancer deaths. Traditional therapeutics and immunomodulatory
      agents have not shown much efficacy against metastatic melanoma. Agents that
      target the RAS/RAF/MEK/ERK (MAPK) signaling pathway - the BRAF inhibitors
      vemurafenib and dabrafenib, and the MEK1/2 inhibitor trametinib - have increased
      survival in patients with metastatic melanoma. Further, the combination of
      dabrafenib and trametinib has been shown to be superior to single agent therapy
      for the treatment of metastatic melanoma. However, resistance to these agents
      develops rapidly. Studies of additional agents and combinations targeting the
      MAPK, PI3K/AKT/mTOR (PI3K), c-kit, and other signaling pathways are currently
      underway. Furthermore, studies of phytochemicals have yielded promising results
      against proliferation, survival, invasion, and metastasis by targeting signaling
      pathways with established roles in melanomagenesis. The relatively low toxicities
      of phytochemicals make their adjuvant use an attractive treatment option. The
      need for improved efficacy of current melanoma treatments calls for further
      investigation of each of these strategies. In this review, we will discuss
      synthetic small molecule inhibitors, combined therapies and current progress in
      the development of phytochemical therapies. 

PMID- 25597792
TI  - Continuing education: preparing patients to choose a renal replacement therapy.
AB  - BACKGROUND: Patients with progressive chronic kidney disease face a series of
      treatment decisions that will impact the quality of life of themselves and their
      family. Renal replacement therapy option education (RRTOE), generally provided by
      nurses, is recommended by international guidelines OBJECTIVES: To provide nurses
      with advice and guidance on running RRTOE. DESIGN: A consensus conference.
      PARTICIPANTS: Four nurses, 5 nephrologists and 1 clinical psychologist (9 renal
      units; 6 European countries) from units that had extensive experience in RRTOE or
      were performing research in this field. APPROACH: Experts brainstormed and
      discussed quality standards for the education team, processes, content/topics,
      media/material/funding and quality measurements for RRTOE. RESULTS: Conclusions
      and recommendations from these discussions that are particularly pertinent to
      nurses are presented in this paper. CONCLUSIONS: Through careful planning and
      smooth interdisciplinary cooperation, it is possible to implement an education
      and support programme that helps patients choose a form of RRT that is most
      suited to their needs. This may result in benefits in quality of life and
      clinical outcomes. APPLICATION TO PRACTICE: There are large differences between
      renal units in terms of resources available and the demographics of the catchment
      area. Therefore, nurses should carefully consider how best to adapt the advice
      offered here to their own situation. Throughout this process, it is crucial to
      keep in mind the ultimate goal - providing patients with the knowledge and skill
      to make a modality choice that will enhance their quality of life to the greatest
      degree.

PMID- 25597793
TI  - Protective benefits of mindfulness in emergency room personnel.
AB  - BACKGROUND: Recent meta-analyses have found that mindfulness practice may reduce
      anxiety and depression in clinical populations and there is growing evidence that
      mindfulness may also improve well-being and quality of care in health
      professionals. This study examined whether mindfulness protects against the
      impact of work-related stress on mental health and burnout in emergency room (ER)
      nurses. METHODS: ER nurses (N=50) were recruited from an urban teaching hospital
      in Switzerland and completed a survey on work-related stressors, mindfulness,
      burnout, depression, and anxiety. RESULTS: The most frequently reported work
      related stressor was interpersonal conflict. Nurses working more consecutive days
      since last taking time off were at greater risk for depression and those
      reporting more work-related interpersonal conflicts were at greater risk for
      burnout. Mindfulness was associated with reduced anxiety, depression, and
      burnout. Mindfulness was a significant predictor of anxiety, depression, and
      burnout and moderated the impact of work-related stressors on mental health and
      burnout. LIMITATIONS: The sample is limited to nurses and results need to be
      replicated in other groups (e.g., medical staff or ambulance workers). We
      assessed clinical symptoms with questionnaires and it would be desirable to
      repeat this assessment with clinical diagnostic interviews. CONCLUSIONS: The
      findings have implications for stress management in ER nurses and health
      professionals working in comparable settings (e.g., urgent care). The robust
      associations between mindfulness and multiple indices of psychological well-being
      suggest that ER staff exposed to high levels of occupational stress may benefit
      from mindfulness practice to increase resistance to mental health problems and
      burnout.

PMID- 25597794
TI  - Childhood traumatic experiences of patients with bipolar disorder type I and type
      II.
AB  - BACKGROUND: Childhood trauma is an important environmental stressor associated
      with bipolar disorders (BD). It is still not clear if it is differently
      distributed between BD I and BD II. Therefore, the aim of this research was to
      investigate the distribution patterns of childhood trauma in BD I and BD II. In
      this perspective, we also studied the relationship between childhood trauma and
      suicidality. METHODS: We assessed 104 outpatients diagnosed with BD I (n=58) or
      BD II (n=46) according to DSM-IV-TR criteria and 103 healthy controls (HC)
      matched for age, sex and education level. History of childhood trauma was
      obtained using the Childhood Trauma Questionnaire (CTQ). RESULTS: All patients
      with BD had had more severe traumatic childhood experiences than HC. Both BD I
      and BD II patients differed significantly from HC for trauma summary score and
      emotional abuse. BD I patients differed significantly from HC for sexual abuse,
      and BD II differed from HC for emotional neglect. BD I and BD II did not
      significantly differ for any type of trauma. Suicide attempts were linked to both
      emotional and sexual abuse in BD I and only to emotional abuse in BD II.
      Emotional abuse was an independent predictor of lifetime suicide attempts in BD
      patients. LIMITATIONS: The reliability of the retrospective assessment of
      childhood trauma experiences with the CTQ during adulthood may be influenced by
      uncontrolled recall bias. CONCLUSIONS: The assessment of childhood trauma, which
      has great clinical importance because of its strong link with suicidality, can
      unveil slight differences between BD subtypes and HC.

PMID- 25597795
TI  - A longitudinal study of the association of adiponectin gene rs1501299 with
      depression in Chinese Han adolescents after Wenchuan earthquake.
AB  - BACKGROUND: Previous studies showed inconsistent results of the association
      between plasma adiponectin and depression. The aim of this study is to
      longitudinally investigate the association of adiponectin rs1501299 with
      depression in Chinese Han adolescents who experienced the 2008 Wenchuan
      earthquake. METHOD: Variants of adiponectin rs1501299 were identified by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. Depressive symptoms were assessed by Beck Depression Inventory (BDI)
      among 746 high school students at 6, 12 and 18 months after the earthquake.
      RESULTS: The female T allele carriers of adiponectin rs1501299 had lower
      prevalence of depression (p=0.008) and BDI scores (p=0.024) than the female GG
      homozygotes at 18 months, but not at 6 or 12 months after the earthquake, which
      were significantly reduced (p=0.022 for the prevalence and p<0.001 for the
      scores) in the female T allele carriers at 18 months after the earthquake when
      compared with those at 12 months. In addition, the major predictors of depression
      for the GG homozygotes were gender and age at 6, 12 and 18 months after
      earthquake. On the other hand, the major predictor for the T allele carriers was
      gender at 6, 12 and 18 months after earthquake. LIMITATIONS: There were some
      limitations in the present study. First, adiponectin expressions including serum
      adiponectin and mRNA in adipose tissues were not measured. Second, the effect of
      body mass index was not evaluated. CONCLUSIONS: The adiponectin T allele is
      associated with reduced prevalence of depression and lower BDI scores of female
      adolescents in the later stage of rehabilitation of depression.

PMID- 25597796
TI  - New developments in the extraction and determination of parabens in cosmetics and
      environmental samples. A review.
AB  - Parabens are a family of synthetic esters of p-hydroxibenzoic acid widely used as
      preservatives in cosmetics and health-care products, among other daily-use
      commodities. Recently, their potential endocrine disrupting effects have raised
      concerns about their safety and their potential effects as emerging pollutants,
      leading to the regulation of the presence of parabens in commercial products by
      national and trans-national organizations. Also, this has led to an interest in
      developing sensible and reliable methods for their determination in environmental
      samples, cosmetics and health-care products. This paper is a comprehensive up-to
      date review of the literature concerning the determination of parabens in
      environmental samples and cosmetic and health-care products. A brief revision of
      the literature concerning the traditional determination of parabens (1980-2003)
      is included, followed by an in-depth revision of the recent developments in both
      measurement and extraction methods for parabens in the last years (2003-2013).
      Finally, possible future perspectives in this field are proposed. 

PMID- 25597797
TI  - A consensus successive projections algorithm--multiple linear regression method
      for analyzing near infrared spectra.
AB  - The successive projections algorithm (SPA) is widely used to select variables for
      multiple linear regression (MLR) modeling. However, SPA used only once may not
      obtain all the useful information of the full spectra, because the number of
      selected variables cannot exceed the number of calibration samples in the SPA
      algorithm. Therefore, the SPA-MLR method risks the loss of useful information. To
      make a full use of the useful information in the spectra, a new method named
      "consensus SPA-MLR" (C-SPA-MLR) is proposed herein. This method is the
      combination of consensus strategy and SPA-MLR method. In the C-SPA-MLR method,
      SPA-MLR is used to construct member models with different subsets of variables,
      which are selected from the remaining variables iteratively. A consensus
      prediction is obtained by combining the predictions of the member models. The
      proposed method is evaluated by analyzing the near infrared (NIR) spectra of corn
      and diesel. The results of C-SPA-MLR method showed a better prediction
      performance compared with the SPA-MLR and full-spectra PLS methods. Moreover,
      these results could serve as a reference for combination the consensus strategy
      and other variable selection methods when analyzing NIR spectra and other
      spectroscopic techniques. 

PMID- 25597798
TI  - An analytical multi-residue approach for the determination of semi-volatile
      organic pollutants in pine needles.
AB  - Vegetation (and pine needles in particular) has been widely used as an
      alternative to other conventional sampling devices to assess the atmospheric
      presence of semi-volatile organic contaminants (SVOCs). While most analytical
      procedures developed focus only on one or two chemical classes, this this work
      intends to establish a multi-component protocol to quantify brominated flame
      retardants (BFRs), polychlorinated biphenyls (PCBs), organochlorine pesticides
      (OCPs), polynuclear aromatic hydrocarbons (PAHs) and one class of contaminant of
      emerging concern, the synthetic musks fragrances (SMCs). Pine needles extracts
      were obtained by ultrasonic solvents extraction (USE), and different cleanup
      approaches using solid-phase extraction (SPE) employing combinations of sorbents
      and solvents as well as gel permeation chromatography (GPC) were tested. SPE with
      alumina followed by GCP yielded the best results, with average recoveries over
      80%. The application of the method under field conditions was proven by the
      analysis of naturally contaminated samples from 3 sites of different potential
      exposure (remote, rural and urban). The total detected concentrations ranged from
      0.45 to 0.87 ng g(-1) dry weight (dw) for BFRs, 0.35 to 1.01 ng g(-1) (dw) for
      PCBs, 0.36 to 12.2 ng g(-1) (dw) for HCB, 245.7 to 967.8 ng g(-1) (dw) for PAHs
      and 20.7 to 277.5 ng g(-1) (dw) for SMCs. This methodology is a viable approach
      for the simultaneous analysis of five different classes of atmospheric pollutants
      employing less analytical efforts. Moreover, to the author's best knowledge, this
      is also the first time vegetation is employed in the detection of SMCs.

PMID- 25597799
TI  - Untargeted metabolomic analysis using liquid chromatography quadrupole time-of
      flight mass spectrometry for non-volatile profiling of wines.
AB  - The current study presents a method for comprehensive untargeted metabolomic
      fingerprinting of the non-volatile profile of the Graciano Vitis vinifera wine
      variety, using liquid chromatography/electrospray ionization time of flight mass
      spectrometry (LC-ESI-QTOF). Pre-treatment of samples, chromatographic columns,
      mobile phases, elution gradients and ionization sources, were evaluated for the
      extraction of the maximum number of metabolites in red wine. Putative compounds
      were extracted from the raw data using the extraction algorithm, molecular
      feature extractor (MFE). For the metabolite identification the WinMet database
      was designed based on electronic databases and literature research and includes
      only the putative metabolites reported to be present in oenological matrices. The
      results from WinMet were compared with those in the METLIN database to evaluate
      how much the databases overlap for performing identifications. The
      reproducibility of the analysis was assessed using manual processing following
      replicate injections of Vitis vinifera cv. Graciano wine spiked with external
      standards. In the present work, 411 different metabolites in Graciano Vitis
      vinifera red wine were identified, including primary wine metabolites such as
      sugars (4%), amino acids (23%), biogenic amines (4%), fatty acids (2%), and
      organic acids (32%) and secondary metabolites such as phenols (27%) and esters
      (8%). Significant differences between varieties Tempranillo and Graciano were
      related to the presence of fifteen specific compounds. 

PMID- 25597800
TI  - Development of gold nanoparticle based colorimetric method for quantitatively
      studying the inhibitors of Cu(2+)/Zn(2+) induced beta-amyloid peptide assembly.
AB  - In this paper, a kind of gold nanoparticle (GNP)-based colorimetric assay has
      been developed for studying the reversible interaction of beta-amyloid peptide
      (Abeta) with Cu(2+) and Zn(2+), and quantitatively analyzing four inhibitors
      (i.e., EDTA, EGTA, histidine and clioquinol) of Cu(2+)/Zn(2+) induced Abeta
      assembly. The inhibition efficiencies (e.g., half maximal inhibitory
      concentration, IC50 value) of these inhibitors could be measured in this work. As
      far as we know, these IC50 values were reported at the first time. In this assay,
      the streptavidin conjugated GNPs (SA-GNPs) were employed as indicators to monitor
      the Cu(2+)/Zn(2+) induced aggregating/disaggregating behaviors of biotin modified
      beta-amyloid 1-16 peptides (Abeta1-16(biotin)). Because of high affinity of
      streptavidin (SA) with biotin, the aggregating/disaggregating of Abeta1
      16(biotin) results in the significant color change of SA-GNPs. Furthermore, we
      demonstrate that the assay can be used as an effective tool for designing anti
      dementia drugs through quantitative analysis of the interactions of four
      representative inhibitors with Cu(2+)/Zn(2+) induced Abeta assembly. 

PMID- 25597801
TI  - CuNiO nanoparticles assembled on graphene as an effective platform for enzyme
      free glucose sensing.
AB  - We utilized CuNiO nanoparticles modified graphene sheets (CuNiO-graphene) to the
      application of enzymeless glucose sensing. The hydrothermal synthesized CuNiO
      nanoparticles were successfully assembled on graphene sheets. Distinct from
      general method, the high quality pristine graphene was produced by chemical vapor
      deposition (CVD) and bubbling transferred on the electrode. Incorporating the
      excellent electronic transport of graphene and high electrocatalytic activity of
      CuNiO nanoparticles, the CuNiO-graphene nanocomposite modified electrode
      possessed strong electrocatalytic ability toward glucose in alkaline media. The
      proposed nonenzymatic glucose sensor exhibited wide linear range up to 16 mM (two
      parts, from 0.05 to 6.9 mM and 6.9-16 mM) and high sensitivity (225.75 MUA mM(-1)
      cm(-2) and 32.44 MUA mM(-1) cm(-2), respectively). Excellent selectivity and
      acceptable stability were also achieved. Such an electrode would be attractive to
      sensor construction for its good properties, simple operation and low expense.

PMID- 25597802
TI  - An ultrasensitive method of real time pH monitoring with complementary metal
      oxide semiconductor image sensor.
AB  - CMOS sensors are becoming a powerful tool in the biological and chemical field.
      In this work, we introduce a new approach on quantifying various pH solutions
      with a CMOS image sensor. The CMOS image sensor based pH measurement produces
      high-accuracy analysis, making it a truly portable and user friendly system. pH
      indicator blended hydrogel matrix was fabricated as a thin film to the accurate
      color development. A distinct color change of red, green and blue (RGB) develops
      in the hydrogel film by applying various pH solutions (pH 1-14). The semi
      quantitative pH evolution was acquired by visual read out. Further, CMOS image
      sensor absorbs the RGB color intensity of the film and hue value converted into
      digital numbers with the aid of an analog-to-digital converter (ADC) to determine
      the pH ranges of solutions. Chromaticity diagram and Euclidean distance represent
      the RGB color space and differentiation of pH ranges, respectively. This
      technique is applicable to sense the various toxic chemicals and chemical vapors
      by situ sensing. Ultimately, the entire approach can be integrated into
      smartphone and operable with the user friendly manner. 

PMID- 25597803
TI  - Potentiometric flow injection sensing system for determination of heparin based
      on current-controlled release of protamine.
AB  - A flow injection system incorporated with a polycation-sensitive polymeric
      membrane electrode in the flow cell is proposed for potentiometric determination
      of heparin. An external current in nano-ampere scale is continuously applied
      across the polymeric membrane for controlled release of protamine from the inner
      filling solution to the sample solution, which makes the electrode membrane
      regenerate quickly after each measurement. The protamine released at membrane
      sample interface is consumed by heparin injected into the flow cell via their
      strong electrostatic interaction, thus decreasing the measured potential, by
      which heparin can be detected. Under optimized conditions, a linear relationship
      between the potential peak height and the concentration of heparin in the sample
      solution can be obtained in the range of 0.1-2.0 U mL(-1), and the detection
      limit is 0.06 U mL(-1). The proposed potentiometric sensing system has been
      successfully applied to the determination of heparin in undiluted sheep whole
      blood.

PMID- 25597804
TI  - A fast and effective routine method based on HS-SPME-GC-MS/MS for the analysis of
      organotin compounds in biota samples.
AB  - This work validated an automated, fast, and low solvent- consuming methodology
      suited for routine analysis of tributyltin (TBT) and degradation products
      (dibutyltin, DBT; monobutyltin, MBT) in biota samples. The method was based on
      the headspace solid-phase microextraction methodology (HS-SPME), coupled with gas
      chromatographic separation and tandem mass-spectrometry (GC-MS/MS). The
      effectiveness of the matrix-matched signal ratio external calibration was tested
      for quantification purposes. The exclusion of matrix influences in the
      calibration curves proved the suitability of this versatile quantification
      method. The method detection limits obtained were of 3 ng Sn g(-1) dw for all the
      analytes. The analysis of references materials showed satisfying accuracy under
      optimum calibration conditions (% recovery between 87-111%; |Z-scores|<2). The
      repeatability RSD% and intra-laboratory reproducibility RSD% were lower than 9.6%
      and 12.6%, respectively. The work proved the remarkable analytical performances
      of the method and its high potential for routine application in monitoring
      organotin compounds (OTC).

PMID- 25597805
TI  - Bulk derivatization and cation exchange restricted access media-based trap-and
      elute liquid chromatography-mass spectrometry method for determination of trace
      estrogens in serum.
AB  - Estrone (E1), estradiols (alpha/beta-E2), and estriol (E3) are four major
      metabolically active estrogens exerting strong biological activities at very low
      circulating concentrations. This paper reports a sensitive and efficient method
      with automated, on-line clean-up and detection to determine trace estrogens in a
      small volume of serum samples using liquid chromatography-electrospray ionization
      tandem mass spectrometry directly, without off-line liquid-liquid or solid-phase
      extraction pretreatments. Serum aliquots (charcoal stripped fetal bovine serum,
      100 MUL) were spiked with four estrogen standards and their corresponding isotope
      labeled internal standards, then bulk derivatized with 2-fluoro-1-methyl-pyridium
      p-toluenesulfonate (2-FMP) to establish the calibration curves and perform method
      validation. Calibration was established in the concentration ranges of 5-1000 pg
      mL(-1), and demonstrated good linearity of R(2) from 0.9944 to 0.9997 for the
      four derivatized estrogens. The lower detection limits obtained were 3-7 pg mL(
      1). Good accuracy and precision in the range of 86-112% and 2.3-11.9%,
      respectively, were observed for the quality control (QC) samples at low, medium,
      and high concentration levels. The stability tests showed that the derivatized
      serum samples were stable 8h after derivatization at room temperature and at
      least to 48 h if stored at -20  degrees C. The method was applied to measure
      trace estrogens in real human and bovine serum samples, and three of four
      estrogen compounds studied were observed and quantified.

PMID- 25597806
TI  - A simple method for patterning poly(dimethylsiloxane) barriers in paper using
      contact-printing with low-cost rubber stamps.
AB  - This paper presents a simple and low-cost method for patterning
      poly(dimethylsiloxane) (PDMS) barriers in porous support such as paper for the
      construction of flexible microfluidic paper-based analytical devices (MUPADs).
      The fabrication method consisted of contact-printing a solution of PDMS and
      hexane (10:1.5 w/w) onto chromatographic paper using custom-designed rubber
      stamps containing the patterns of MUPADs. After penetrating the paper (~30 s),
      the PDMS is cured to form hydrophobic barriers. Under optimized conditions,
      hydrophobic barriers and hydrophilic channels with dimensions down to 949+/-88
      MUm and 771+/-90 MUm (n=5), respectively, were obtained. This resolution is well
      suitable for most applications in analytical chemistry. Chemical compatibility
      studies revealed that the PDMS barriers were able to contain some organic
      solvents, including acetonitrile and methanol, and aqueous solutions of some
      surfactants. This find is particularly interesting given that acetonitrile and
      methanol are the most used solvents in chromatographic separations, non-aqueous
      capillary electrophoresis and electroanalysis, as well as aqueous solutions of
      surfactants are suitable mediums for cell lyses assays. The utility of the
      technique was evaluated in the fabrication of paper-based electrochemical devices
      (PEDs) with pencil-drawn electrodes for experiments in static cyclic voltammetry
      and flow injection analysis (FIA) with amperometric detection, in both aqueous
      and organic mediums.

PMID- 25597807
TI  - Rapid concentration of deoxyribonucleic acid via Joule heating induced
      temperature gradient focusing in poly-dimethylsiloxane microfluidic channel.
AB  - This paper reports rapid microfluidic electrokinetic concentration of
      deoxyribonucleic acid (DNA) with the Joule heating induced temperature gradient
      focusing (TGF) by using our proposed combined AC and DC electric field technique.
      A peak of 480-fold concentration enhancement of DNA sample is achieved within 40s
      in a simple poly-dimethylsiloxane (PDMS) microfluidic channel of a sudden
      expansion in cross-section. Compared to a sole DC field, the introduction of an
      AC field can reduce DC field induced back-pressure and produce sufficient Joule
      heating effects, resulting in higher concentration enhancement. Within such
      microfluidic channel structure, negative charged DNA analytes can be concentrated
      at a location where the DNA electrophoretic motion is balanced with the bulk flow
      driven by DC electroosmosis under an appropriate temperature gradient field. A
      numerical model accounting for a combined AC and DC field and back-pressure
      driven flow effects is developed to describe the complex Joule heating induced
      TGF processes. The experimental observation of DNA concentration phenomena can be
      explained by the numerical model. 

PMID- 25597808
TI  - Hyperthermia process control induced by the electric field in order to destroy
      cancer.
AB  - PURPOSE: The paper presents numerical modeling of the artificial hyperthermia
      induced by the electric field in order to destroy the abnormal tissue. In
      particular, the possibility of process control in order to increase the
      temperature of only the tumor tissue was discussed. Due to the fact that the
      external electrodes which generate the additional heat, heat not only the area of
      the tumor, but also healthy tissue which surrounds the tumor, increasing the
      temperature inside the cancer is possible by introducing the paramagnetic
      nanoparticles into the interior. Additionally, the proper selection of voltage on
      the electrodes and the number of nanoparticles will enable optimal effect of
      hyperthermia treatment to be achieved. METHODS: The multiple reciprocity BEM is
      applied to solve the coupled problem connected with the biological tissue
      heating. In order to determine the appropriate values of the parameters the
      inverse problem has been formulated, connected with simultaneous identification
      of the voltage of the electrodes and the number of nanoparticles, which is solved
      using the evolutionary algorithm. RESULTS: The changes of the voltage of
      electrodes cause the changes of temperature in the entire domain considered, but
      the possibilities of temperature field control (e.g., concentration of maximum
      temperature at the central point of tumor) are rather unrealizable, because the
      maximum temperature we could observe in the neighbourhood of the electrodes.
      CONCLUSIONS: The idea consisting in the introduction of nanoparticles to the
      tumor region (for the concentrated energy deposition at the target tissue) is
      very effective. We obtain the maximum temperature exactly in the tumor domain.

PMID- 25597810
TI  - Selective hydration of nitriles to amides catalysed by PCP pincer supported
      nickel(II) complexes.
AB  - The (PCP)Ni-OH complexes (R = (i)Pr, (t)Bu, Cy) are effective catalyst precursors
      for the selective hydration of nitriles to the corresponding amides under
      relatively mild conditions (80  degrees C) and low catalyst loadings (0.05-0.5%).
      Substrate scope includes aliphatic, vinylic and aromatic nitriles, but substrates
      with protic groups poison the catalyst abruptly. The catalysts are effective
      because the electron rich nature of the PCP ligands and their steric bulk renders
      the hydroxo group labile. 

PMID- 25597809
TI  - Characterization of somatosensory profiles in patients with Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is a painful chronic inflammatory bowel disease.
      It primarily affects terminal ileum, but the involvement of large and small
      intestines or extraintestinal manifestations is very common. CD may go along with
      neurogenic inflammation, mediated by substance P and CGRP, which are also key
      players in pain transmission. This may in turn contribute to hyperalgesia and
      altered somatosensory function in CD. METHODS: One hundred and three (103)
      patients with CD and 80 healthy volunteers were enrolled. Patient characteristics
      and disease history were documented. We used quantitative sensory testing (QST)
      to investigate the somatosensory profile in patients and volunteers. We also
      calculated z-scores for the QST results of the patients with CD based on the data
      of our control group. A 2-step cluster analysis, using all QST data, was
      performed to find subgroups within patients and volunteers. RESULTS: Thresholds
      of warm detection, mechanical pain, and vibration detection did significantly
      differ between patients with CD and volunteers. Z-scores indicated a general
      trend of sensory loss in CD patients with a significant relationship between
      patients with a sensory loss for cold and warm detection. In the hyposensitive
      cluster of the CD cohort, patients were more frequently male, had a higher
      incidence of extraintestinal manifestations, and suffered longer from CD.
      CONCLUSIONS: Our findings are consistent with the presence of a subclinical small
      fiber neuropathy. The group of CD patients with pronounced neuropathy findings
      were predominantly males, had a higher incidence of extraintestinal
      manifestations, and tended to have a longer history of disease duration.

PMID- 25597811
TI  - Multi-level synchrotron radiation-based microtomography of the dental alveolus
      and its consequences for orthodontics.
AB  - Multilevel synchrotron radiation-based microtomography has been performed on a
      human jaw segment obtained at autopsy by cutting increasingly smaller samples
      from the original segment. The focus of this study lay on the microstructure of
      the interface between root, periodontal ligament (PDL) and alveolar bone in order
      to find an answer to the question why alveolar bone remodels during orthodontic
      loading, when the associated stress and strain levels calculated with finite
      element analyses are well below the established threshold levels for bone
      remodeling. While the inner surface of the alveolus appears to be rather smooth
      on the lower resolution scans, detailed scans of the root-PDL-bone interface
      reveal that on a microscopical scale it is actually quite rough and uneven with
      bony spiculae protruding into the PDL space. Any external (orthodontic) loading
      applied to the root, when transferred through the PDL to the alveolar bone, will
      cause stress concentrations in these spiculae, rather than be distributed over a
      "smooth surface". As osteocyte lacunae are shown to be present in these spiculae,
      the local amplified stresses and strain can well be registered by the mechano
      sensory network of osteocytes. In addition, a second stress amplification
      mechanism, due to the very presence of the lacunae themselves, is evidence that
      stresses and strains calculated with FE analyses, based on macroscopical scale
      models of teeth and their supporting structures, grossly underestimate the actual
      mechanical loading of alveolar bone at tissue level. It is therefore hypothesized
      that remodeling of alveolar bone is subject to the same biological regulatory
      process as remodeling in other bones. 

PMID- 25597812
TI  - Thermal shock cycling effect on the compressive behaviour of human teeth.
AB  - All ceramic veneers are a common choice that both dentists and patients make for
      anterior restorations. In the framework of the present study the residual
      compressive behavior of the above mentioned complex structures after being
      thermally shock cycled was investigated. An exponential decrease in both
      compressive stiffness and strength with the thermal shock cycle number was
      observed. Experimental findings were in good agreement with predicted values.
      Photomicrographs obtained revealed a different failure mechanism for the pristine
      and cycled teeth, which is indicative of the susceptible nature of restored teeth
      to thermal shock. A two-dimensional finite element model designed gave a better
      insight upon the stress fields in response of thermal or mechanical loadings
      developed in the oral cavity. 

PMID- 25597813
TI  - Analyzing center of rotation during opening and closing movements of the mandible
      using computer simulations.
AB  - The traditional hinge axis theory for guiding clinical procedures in dentistry
      and dental articulators has been challenged by the concept of an instantaneous
      center of rotation (ICR), which is becoming more prevalent in modern explanations
      of mandibular movement. The purpose of this study was to analyze traditional
      hinge axis theory using three-dimensional computer simulations and to compare it
      with ICR. Three-dimensional computational models that reproduced the traditional
      pantograph tracing method were created to simulate the opening and closing
      movements of the jaw. Models of the bones, muscles and ligaments were combined to
      create a dynamic representation using ArtiSynth, a biomechanical simulation
      toolkit. The mandibular motion is constrained based on contact between the
      articular eminence and the mandibular condyle, and is limited by spring-like
      ligaments, as well as passive properties of the skeletal muscles. To estimate the
      center of rotation according to the traditional axis theory, markers on the
      pantograph were traced during mandibular opening and closing movement. The ICR
      was computed at each time step throughout the simulation. To locate a single
      hinge axis in simulation, the point about which the mandible seems to rotate
      during early opening and terminal closing was determined. The estimated center of
      rotation was inconsistent with the ICR, yet motion was found to be well
      approximated by a pure rotation. The inconsistency suggests that the use of the
      ICR position for the clinical dental procedures has its limitations. 

PMID- 25597814
TI  - Increase in joint stability at the expense of energy efficiency correlates with
      force variability during a fatiguing task.
AB  - Empirical evidence suggests that our nervous system considers many objectives
      when performing various tasks. With the progression of fatigue, researchers have
      noted increase in both joint moment variability and muscular cocontraction during
      isometric force production tasks. Muscular cocontraction increases joint
      stability, but is metabolically costly. Thus, our nervous system must select a
      compromise between joint stability and energy efficiency. Interestingly, the
      continuous increase in cocontraction with fatigue suggests there may be a shift
      in the relative weighting of these objectives. Here we test the notion of dynamic
      objective weightings. Using multi-objective optimization, we found a shift in
      objective weighting that favoured joint stability at the expense of energy
      efficiency during fatigue. This shift was highly correlated with muscular
      cocontraction (R(2)=0.78, p<0.001) and elbow moment variability in the time
      (R(2)=0.56, p<0.01) and frequency (R(2)=0.57, p<0.01) domains. By considering a
      dynamic objective weighting we obtained strong correlations with predicted and
      collected muscle activity (R(2)=0.94, p<0.001).

PMID- 25597815
TI  - Numerical characterization of magnetically aligned multiwalled carbon nanotube
      Fe3O4 nanoparticle complex.
AB  - Alignment states of one-dimensional multiwalled carbon nanotubes containing
      various contents of zero-dimensional ferriferrous oxide nanoparticles (MWCNT
      Fe3O4) were numerically characterized. MWCNT-Fe3O4 complexes were successfully
      prepared via in situ surface-initiated atom transfer radical polymerization,
      followed by a coprecipitation process. The complexes showed strong magnetism,
      which endowed them with the ability to be aligned under the action of an external
      magnetic field. The intensity of the magnetic field, loading content of Fe3O4
      nanoparticles, and viscosity of dispersing medium, however, all had substantial
      effects on the alignment degree. To evaluate the alignment effectively and
      quantitatively, an orientation tensor description based on marking the direction
      of a single MWCNT in a selected region of optical images was employed. The
      results showed that MWCNT-Fe3O4 complex containing 26 wt % of Fe3O4 nanoparticles
      achieved a desirable alignment in deionized water under a magnetic field
      intensity of 0.10 T. Accordingly, epoxy composites reinforced with such aligned
      MWCNT-Fe3O4 complexes displayed 12.3 and 10.9% enhancement in tensile strength
      and modulus, as well as 8.9 and 6.1% enhancement in flexural strength and
      modulus, respectively. 

PMID- 25597816
TI  - Monooxygenation of an appended phenol in a model system of tyrosinase:
      implications on the enzymatic reaction mechanism.
AB  - A new tridentate N-donor ligand and its corresponding copper(i) complex have been
      synthesized to investigate the tyrosinase-like aromatic hydroxylation of an
      attached phenol. The results of the oxygenation reactions are compared to related
      systems having attached phenyl and catechol groups, respectively. The title
      complex is the first system mediating the monooxygenation of a phenol in the
      absence of an external base. 

PMID- 25597818
TI  - Facile fabrication of wafer-scale MoS2 neat films with enhanced third-order
      nonlinear optical performance.
AB  - Wafer-scale MoS2 neat films with controllable thicknesses were successfully
      fabricated by vacuum filtering liquid-exfoliated MoS2 dispersions. The obtained
      MoS2 filtered thin films were systematically characterized by UV-Vis
      spectroscopy, Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy,
      atomic force microscopy (AFM) and scanning electron microscopy (SEM). It was
      found that the fabricated scalable MoS2 films have a smooth surface and high
      optical homogeneity verified by AFM and a collimated 532 nm beam, respectively.
      We investigated the ultrafast nonlinear optical (NLO) properties of the filtered
      films by an open aperture Z-scan method using 515 and 1030 nm femtosecond laser
      pulses. Saturable absorption was observed at both 515 and 1030 nm with the figure
      of merit (FOM) values as ~3.3 * 10(-12) esu cm and ~3.4 * 10(-14) esu cm,
      respectively. The observation of ultrafast NLO performance of the MoS2 filtered
      films indicates that vacuum filtration is a feasible method for the fabrication
      of optical thin films, which can be expanded to fabricate other two-dimensional
      films from the corresponding dispersions. This easy film fabrication technology
      will greatly enlarge the application of graphene analogues including graphene in
      photonic devices, especially of MoS2 as a saturable absorber. 

PMID- 25597817
TI  - The impact of cryopreservation on human  peripheral blood leucocyte
      bioenergetics.
AB  - Circulating immune cells are considered a source for biomarkers in health and
      disease, since they are exposed to nutritional, metabolic and immunological
      stimuli in the vasculature. Cryopreservation of leucocytes is routinely used for
      long-term storage and determination of phenotypic/functional changes at a later
      date. Exploring the role of bioenergetics and mitochondrial (dys)function in
      leucocytes is often examined by using freshly isolated cells. The aim of the
      pilot study described herein was to assess leucocyte bioenergetics in
      cryopreserved cells. Leucocytes were isolated from whole blood, counted and
      frozen in liquid nitrogen (LN2) for a period of 3 months. Cells were thawed at
      regular intervals and bioenergetic analysis performed using the Seahorse XFe96
      flux analyser. Cryogenic storage reduced cell viability by 20%, but cell
      bioenergetic responses were largely intact for up to 1 month storage in LN2.
      However, after 1 month storage, mitochondrial function was impaired as reflected
      by decreasing basal respiration, ATP production, maximum (MAX) respiration,
      reserve capacity and coupling efficiency. Conversely, glycolytic activity was
      increased after 1 month, most notably the enhanced glycolytic response to 25 mM
      glucose without any change in glycolytic capacity. Finally, calculation of
      bioenergetic health index (BHI) demonstrated that this potential diagnostic
      parameter was sensitive to cryopreservation. The present study has demonstrated
      for the first time that cryopreservation of primary immune cells modified their
      metabolism in a time-dependent fashion, indicated by attenuated aerobic
      respiration and enhanced glycolytic activity. Taken together, we recommend
      caution in the interpretation of bioenergetic responses or BHI in cryopreserved
      samples.

PMID- 25597819
TI  - Silicone-grafted carbonaceous nanotubes with enhanced dispersion stability and
      electrorheological efficiency.
AB  - Carbonaceous particles are types of important fillers or dispersed phases of
      electro-responsive electrorheological (ER) suspensions. But carbonaceous
      particles, in particular with nano-order size, are easy to aggregate in oils.
      This characteristic limits the application of ER suspensions based on
      carbonaceous particles. In order to improve dispersion stability and ER
      efficiency, in this paper, we develop silicone-grafted carbonaceous nanotubes
      (CTs) by grafting oxidized carbonaceous nanotubes with epoxy-terminated silicone.
      The samples are characterized by Fourier transform infrared spectra, x-ray
      photoelectron spectroscopy, thermogravimetric analysis, and transmission electron
      microscopy. The wettability and dispersion stability of nanotubes in silicone oil
      are investigated by wetting curves and sedimentation tests. The ER properties of
      CTs when dispersed in silicone oil are measured by a rheometer under electric
      fields. It demonstrates that grafting with silicone can distinctly improve the
      wettability of CTs in silicone oil and decrease the re-aggregation of CTs. As a
      result, the suspension of silicone-grafted CTs in silicone oil shows high
      dispersion stability. Compared to the suspension of bare CTs, the suspension of
      silicone-grafted CTs exhibits lower zero-field viscosity but higher field-induced
      viscosity; thus it possesses higher ER efficiency. This enhanced ER efficiency is
      related to the improved wettability of silicone-grafted CTs in silicone oil. 

PMID- 25597820
TI  - Electrical detection of dengue biomarker using egg yolk immunoglobulin as the
      biological recognition element.
AB  - Nonstructural protein 1 (NS1) is secreted by dengue virus in the first days of
      infection and acts as an excellent dengue biomarker. Here, the direct electrical
      detection of NS1 from dengue type 2 virus has been achieved by the measurement of
      variations in open circuit potential (OCP) between a reference electrode and a
      disposable Au electrode containing immobilized anti-NS1 antibodies acting as
      immunosensor. Egg yolk immunoglobulin (IgY) was utilized for the first time as
      the biological recognition element alternatively to conventional mammalian
      antibodies in the detection of dengue virus NS1 protein. NS1 protein was detected
      in standard samples in a 0.1 to 10 ug.mL(-1) concentration range with (3.2 +/-
      0.3) mV/ug.mL(-1) of sensitivity and 0.09 ug.mL(-1) of detection limit.
      Therefore, the proposed system can be extended to detect NS1 in real samples and
      provide an early diagnosis of dengue. 

PMID- 25597821
TI  - Follow-up cultures for MRSA after eradication therapy: are three culture-sets
      enough?
AB  - OBJECTIVES: We compared the standard procedure of three MRSA follow-up culture
      sets to six to determine the number of recurrences detected between the third and
      sixth follow-up culture-set, and studied possible risk factors for MRSA
      recurrence. METHODS: A retrospective carrier cohort (2005-2010) was studied. Data
      was collected on MRSA culture-sets, follow-up, risk factors and outcome
      (recurrences during follow-up). We compared outcome between three and six follow
      up MRSA culture sets, between HCWs and patients groups for complicated or
      uncomplicated carriers, and between nose-throat carriers and other carriers.
      RESULTS: Of 406 MRSA carriers, 179 had received eradication therapy and had a
      negative first follow-up MRSA culture-set. Between the third and sixth follow-up
      culture-set 54% (35/65) of total recurrences occurred. Over 88% of all
      recurrences were detected within two months. Combined nose and throat carriage OR
      25.5 (1.6-419.1)) and intravascular lines (OR 13.6 (1.2-156.2)) were risk factors
      for early recurrence. CONCLUSIONS: We recommend five culture-sets till one year
      after successful eradication therapy with a distinction between those at risk for
      early recurrence and HCWs who require frequent culturing in the beginning and
      those not at risk for early recurrence. This recommendation is a balance between
      the need for swift detection of MRSA recurrence and the patients' burden.

PMID- 25597822
TI  - HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity.
AB  - OBJECTIVES: HIV-1 patients show increased platelet activation, but the mechanisms
      involved are not completely clarified. We speculated that HIV-1 might induce in
      vivo platelet activation by enhancing platelet NOX2-related oxidative stress.
      METHODS: We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet
      activation, in 36 HIV-1 patients under effective combined antiretroviral therapy
      (cART) and in 10 naive HIV-1 subjects. As control, 20 healthy subjects (HS) were
      included. Platelet oxidative stress was measured by platelet NOX2-derived peptide
      (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet
      prostaglandin F2alpha (8-iso-PGF2alpha). RESULTS: sCD40L was increased both in
      HIV-1 naive and cART patients compared to HS (p < 0.001). Platelet sNOX2-dp and 8
      iso-PGF2alpha were significantly higher in HIV-1 naive subjects compared to those
      on cART and to HS, and both were mutually correlated (R = 0.734, p < 0.001). A
      stepwise multivariable linear regression analysis showed that platelet sNOX2-dp
      (beta: 0.803, p < 0.001), HIV-1 infection (beta: 0.146, p = 0.014) and age (beta:
      0.166, p = 0.001) were independently associated to sCD40L levels. CONCLUSIONS:
      HIV-1 infection is associated with increased platelet oxidative stress, which was
      related to the activation of NOX2. The independent association between platelet
      NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet
      activation may be dependent upon platelet oxidative stress.

PMID- 25597823
TI  - Immune reconstitution inflammatory syndrome in neutropenic patients with invasive
      pulmonary aspergillosis.
AB  - OBJECTIVES: Clinical and radiologic deterioration is sometimes observed during
      neutrophil recovery in patients with invasive pulmonary aspergillosis (IPA). This
      deterioration can be caused by immune reconstitution inflammatory syndrome (IRIS)
      as well as by progression of the IPA. However, there is limited data on IRIS in
      neutropenic patients. METHODS: Over a 6-year period, adult patients with
      neutropenia who met the criteria for probable or proven IPA by the revised
      EORTC/MSG definition were retrospectively enrolled. IRIS was defined as de novo
      appearance or worsening of radiologic pulmonary findings temporally related to
      neutrophil recovery, with evidence of a decrease of 50% in serum galactomannan
      level. RESULTS: Of 153 patients, 36 (24%, 95% CI 18%-31%) developed IRIS during
      neutrophil recovery. More of these patients received voriconazole than did those
      with non-IRIS (42% vs. 25%, P = 0.05). Thirty- and ninety-day mortalities were
      lower in the patients with IRIS than in those with non-IRIS (11% vs. 33%, P =
      0.01, and 33% vs. 58%, P = 0.01, respectively). CONCLUSION: IRIS is relatively
      common among neutropenic patients with IPA, occurring in about one quarter of
      such patients. It is associated with voriconazole use and has a good prognosis.

PMID- 25597824
TI  - Rapid diagnosis of cryptococcosis using an antigen detection
      immunochromatographic test.
AB  - OBJECTIVES: Current methods for cryptococcal antigen detection have some
      limitations. This study aimed at evaluating a lateral flow assay (LFA) for the
      diagnosis of cryptococcosis in a French University medical center. METHODS: A
      retrospective study was performed on samples collected from patients with a
      definitive diagnosis of cryptococcosis (group I 66 samples; 28 patients) or with
      non-Cryptococcus invasive fungal infection (group II 18 samples; 17 patients). In
      addition, 274 samples from 205 consecutive patients, either suspected of
      cryptococcal infection or routinely screened during their follow-up, were
      prospectively tested (group III). Cryptococcal antigen was assayed using LFA and
      an EIA. A latex-based test was used for confirmation. RESULTS: Sensitivity
      calculated on group I and specificity on group II, were respectively at 100% and
      90.0%. Two false positives were related to Trichosporon fungemia. Per-sample
      analysis on group III revealed sensitivity, specificity, positive and negative
      predictive values all at 100% for CSF, and at 100%, 98.9%, 75% and 100%,
      respectively for serum samples. LFA enabled the diagnosis of two cases of
      asymptomatic cryptococcosis. CONCLUSION: The excellent diagnostic value and
      practicality (visual reading results in 15 min) of LFA make it fully appropriate
      for the diagnosis of cryptococcosis in this particular setting.

PMID- 25597825
TI  - Risk factors for false-negative T-SPOT.TB assay results in patients with
      pulmonary and extra-pulmonary TB.
AB  - OBJECTIVES: To investigate the risk factors for false-negative T-SPOT.TB results
      in patients with pulmonary TB (PTB) and extra-pulmonary TB (EPTB). METHODS:
      Patients with suspected TB who underwent valid T-SPOT.TB tests were prospectively
      enrolled at Beijing Chest Hospital between November 2012 and November 2013. Basic
      characters and clinical laboratory findings were compared between true-positive
      and false-negative T-SPOT.TB groups. RESULTS: Of 1928 suspected TB patients, 774
      (530 PTB and 244 EPTB) microbiologically/histopathogenically-confirmed patients
      (636 culture-confirmed) were analyzed. Forty-six PTB patients (8.7%) and 32 EPTB
      patients (13.1%) had negative T-SPOT.TB results. Multivariate analysis showed
      that increased age [odds radio (OR) 2.26, 95% confidence interval (CI) 1.11
      4.58], over-weight (BMI >= 25 kg/m(2), OR 2.43, 95% CI 1.05-5.63), and a longer
      period of illness before hospitalization (>6 months, OR 2.46, 95% CI 1.24-4.92)
      were independent risk factors for false-negative T-SPOT.TB results in PTB
      patients. In EPTB patients, increased age (OR 2.42, 95% CI 1.09-5.35) also showed
      an independent association with false-negative T-SPOT.TB results. CONCLUSION:
      Careful interpretation of negative T-SPOT.TB results is necessary in older
      patients with suspected PTB or EPTB, and in PTB patients who are over-weight or
      have had longer periods of illness before hospitalization.

PMID- 25597826
TI  - IP-10 differentiates between active and latent tuberculosis irrespective of HIV
      status and declines during therapy.
AB  - OBJECTIVES: Biomarkers for diagnosis and therapy efficacy in tuberculosis (TB)
      are requested. We have studied biomarkers that may differentiate between active
      and latent TB infection (LTBI), the influence of HIV infection and changes during
      anti-TB chemotherapy. METHODS: Thirty-eight plasma cytokines, assessed by
      multiplex and enzyme immunoassays, were analyzed in patients with active TB
      before and during 24 weeks of anti-TB chemotherapy (n = 65), from individuals
      with LTBI (n = 34) and from QuantiFERON-TB (QFT) negative controls (n = 65). The
      study participants were grouped according to HIV status. RESULTS: Plasma levels
      of the CXC chemokine IP-10 and soluble TNF receptor type 2 (sTNFr2) significantly
      differentiated active TB from the LTBI group, irrespective of HIV status. In the
      HIV-infected group the sensitivity and specificity was 100% for IP-10 with a cut
      off of 2547 pg/mL. Plasma IP-10 declined gradually during anti-TB chemotherapy
      (12-24 weeks, p = 0.002) to a level comparable to LTBI and QFT negative control
      groups. sTNFr2 fluctuated throughout therapy, but was decreased after 12-24 weeks
      (p = 0.006). CONCLUSIONS: IP-10 distinguished with high accuracy active TB from
      LTBI irrespective of HIV infection and declined during anti-TB chemotherapy.
      Plasma IP-10 may serve as a diagnostic biomarker to differentiate between the
      stages of TB infection and for monitoring therapy efficacy.

PMID- 25597827
TI  - Preproinsulin specific CD8+ T cells in subjects with latent autoimmune diabetes
      show lower frequency and different pathophysiological characteristics than those
      with type 1 diabetes.
AB  - Latent autoimmune diabetes in adults (LADA) resembles type 1 diabetes (T1D) in
      disease presentation except that its onset is slow. We compared
      pathophysiological characteristics of CD8+ T cells recognizing preproinsulin
      (PPI) derived epitopes in both disease groups using MHC-I dextramers (DMRs) in
      peripheral blood and after in-vitro stimulation with PPI. Subjects with T1D
      harbored higher frequency of DMR+ CD8+ T cells with relatively higher frequency
      of effector T cell subsets. Following stimulation with PPI, an increase in DMR+
      CD8+ T cells, particularly the central-memory subset was observed in T1D group,
      whereas no significant change in DMR+ CD8+ T cell subsets was observed in LADA
      group. Intracellular expression of Granzyme-B and Perforin in DMR+ CD8+ T cells
      was comparable in both the groups. In conclusion, lower frequency and inferior
      proliferative potential on account of a relatively restrained central-memory
      subset of PPI specific CD8+ T cells are associated with slow rate of disease
      progression in LADA. 

PMID- 25597828
TI  - Diagnostic performance of expression of PCA3, Hepsin and miR biomarkers
      inejaculate in combination with serum PSA for the detection of prostate cancer.
AB  - BACKGROUND AND METHODS: Here, we report on the evaluation of the diagnostic
      performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA
      to detect prostate cancer. cDNA was prepared from 152 candidate specimens
      following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66
      having adequate RNA for all three assays. Small RNA sequencing and examination of
      PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on
      20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS
      classifications and in relation to whole gland histopathology following radical
      prostatectomy. Multivariate logistic regression modeling and clinical risk
      (incorporating standard clinicopathological variables) were performed for all
      ejaculate-based markers. RESULTS: While Hepsin alone was not of predictive value,
      the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate
      composite score based on multivariate logistic regression, was shown to be a
      better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676)
      and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659)
      risk stratification criteria as classified using prostate biopsies. It was also
      possible to analyse a subgroup of patients for miRNA expression with miR-200c
      (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while
      a combination of serum PSA, miR-200c, and miR-125b further improved prediction
      for prostate cancer status when compared to PSA alone determined by biopsy (AUC
      0.869 vs. 0.672; P < 0.05), and risk (D'Amico/PRIAS) as well as by radical
      prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by
      biopsy, at a sensitivity of 90%, the specificity of the test increased from 11%
      for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b.
      CONCLUSIONS: These results show that use of a combination of different types of
      genetic markers in ejaculate together with serum PSA are at least as sensitive as
      those reported in DRE urine. Furthermore, a combination of serum PSA and selected
      miRNAs improved prediction of prostate cancer status. This approach may be
      helpful in triaging patients for MRI and biopsy, when confirmed by larger
      studies.

PMID- 25597829
TI  - [Bmim]2SbCl5: a main group metal-containing ionic liquid exhibiting tunable
      photoluminescence and white-light emission.
AB  - An antimony-based photoluminescent ionic liquid, namely [Bmim]2SbCl5, has been
      synthesized and characterized. It exhibits bright yellow and white light
      emission, with quantum yield as high as 86.3% under UV irradiation. 

PMID- 25597831
TI  - Neonatal haemostasis and the management of neonatal thrombosis.
AB  - Two detailed reviews of the management of neonatal thrombosis were published in
      2012; one was an up-dated version of guidance first issued in 2004 and the other
      was a comprehensive review. Both of these publications gave very similar advice
      regarding the practical aspects of the indications, dosage and management of
      antithrombotic therapy. The authors stated that the evidence supporting most of
      their recommendations for anti-thrombotic therapy in neonates remained weak and
      so the therapy for a neonate with a thrombosis has to be based on an
      individualized assessment of estimated risk versus potential benefit. The aim of
      this present review is to give the treating physician an outline of the unique
      physiology of neonatal coagulation and how this affects the monitoring, dosing
      and even the choice of therapeutic strategy for the management of thrombosis in
      the neonate. 

PMID- 25597832
TI  - Consumer assessment of beef tenderloin steaks from various USDA quality grades at
      3 degrees of doneness.
AB  - A consumer study was conducted to determine palatability ratings of beef
      tenderloin steaks from USDA Choice, USDA Select, and USDA Select with marbling
      scores from Slight 50 to 100 (USDA High Select) cooked to various degrees of
      doneness. Steaks were randomly assigned to 1 of 3 degree of doneness categories:
      very-rare, medium-rare, or well-done. Consumers (N = 315) were screened for
      preference of degree of doneness and fed 4 samples of their preferred doneness (a
      warm-up and one from each USDA quality grade treatment in a random order).
      Consumers evaluated steaks on an 8-point verbally anchored hedonic scale for
      tenderness, juiciness, flavor, and overall like as well as rated steaks as
      acceptable or unacceptable for all palatability traits. Quality grade had no
      effect (P > 0.05) on consumer ratings for tenderness, juiciness, flavor, and
      overall like scores, with all traits averaging above a 7 ("like very much") on
      the 8-point scale. In addition, no differences (P > 0.05) were found in the
      percentage of samples rated as acceptable for all palatability traits, with more
      than 94% of samples rated acceptable for each trait in all quality grades
      evaluated. Steaks cooked to well-done had lower (P < 0.05) juiciness scores than
      steaks cooked to very-rare or medium-rare and were rated lower for tenderness (P
      < 0.05) than steaks cooked to a very-rare degree of doneness. Results indicate
      consumers were not able to detect differences in tenderness, juiciness, flavor,
      or overall like among beef tenderloin steaks from USDA Choice and Select quality
      grades. 

PMID- 25597833
TI  - Substrate stiffness-modulated registry phase correlations in cardiomyocytes map
      structural order to coherent beating.
AB  - Recent experiments show that both striation, an indication of the structural
      registry in muscle fibres, as well as the contractile strains produced by beating
      cardiac muscle cells can be optimized by substrate stiffness. Here we show
      theoretically how the substrate rigidity dependence of the registry data can be
      mapped onto that of the strain measurements. We express the elasticity-mediated
      structural registry as a phase-order parameter using a statistical physics
      approach that takes the noise and disorder inherent in biological systems into
      account. By assuming that structurally registered myofibrils also tend to beat in
      phase, we explain the observed dependence of both striation and strain
      measurements of cardiomyocytes on substrate stiffness in a unified manner. The
      agreement of our ideas with experiment suggests that the correlated beating of
      heart cells may be limited by the structural order of the myofibrils, which in
      turn is regulated by their elastic environment. 

PMID- 25597834
TI  - A new method of sutureless microvascular anastomoses using a thermosensitive
      poloxamer and cyanoacrylate: an experimental study.
AB  - INTRODUCTION: Recently, a new method of sutureless micro-anastomosis based on the
      injection of a termosensitive poloxamer into the vessel lumen and application of
      cyanoacrylate, was described. The long-term results in animals are attractive but
      its use requires a specific heated poloxamer gel and an external heating lamp to
      maintain the surgical site above the transition temperature. The aim of our study
      was to prove the feasibility of this method of sutureless anastomosis with a
      poxolamer gel, which could be used at ambient temperature. MATERIALS AND METHODS:
      Twenty male Sprague-Dawley rats were used. Right common iliac arteries
      anastomoses (RCIA) were performed with the sutureless method (poloxamer gel and
      cyanoacrylate) (SG group) and were compared to left common iliac arteries (LCIA)
      sutured with conventional sutures (CG group). Diameters, duration of
      microvascular anastomosis (DMA) and patency rates were reported. RESULTS: The
      mean diameter of RCIA and LCIA was about 1 mm. The mean DMA for the SG group was
      9.25 +/- 1.45 min and 21.65 +/- 2.96 min in the CG group. Patency rates didn't
      differ between the both groups, either 15 min after anastomosis (CG group 95%
      vs.SG group 100%, P = 0.23) or 15 days after surgery (CG group 90% vs.SG group:
      95%, P = 0.55). Histological analysis showed lower foreign body reaction in
      sutureless group. CONCLUSION: This sutureless method of micro-anastomosis seems
      to be easy to learn and require lower time than conventional sutures. However,
      this technique needs further investigations over the coming years to prove long
      term reliability.

PMID- 25597835
TI  - Anxiety among individuals with visual vertigo and vestibulopathy.
AB  - PURPOSE: Visual vertigo (VV) is a type of dizziness triggered by visual stimuli.
      Despite a high incidence, its relationship with anxiety is not well-defined or
      understood. This study evaluated anxiety levels in subjects with VV compared to
      vestibulopathic subjects without VV and healthy individuals. METHODS: A cross
      sectional study to evaluate anxiety among individuals with VV was conducted
      twice. The first study included 72 participants (66 to 83 years of age) from
      senior residential centers. The second included 31 participants from a vestibular
      rehabilitation program (age range 35-82 years). Study 1 also used the Activities
      Specific Balance Confidence (ABC) scale and study 2 the Dizziness Handicap
      Inventory (DHI). RESULTS: Subjects were classified as VV positive (27 in study 1,
      10 in study 2) or vestibulopathic without VV (30 in study 1, 11 in study 2) based
      on Head Impulse or Dynamic Visual Acuity Tests and the Dizziness Questionnaire.
      The remaining were age-matched healthy controls. The outcome of each study
      demonstrated significantly higher anxiety levels (p = 0.0001) in the VV group
      compared to the other groups. The results of the ABC test demonstrated that
      subjects in the VV group had significantly lower self-confidence (p = 0.001) than
      those in the Vest and Cont groups and performed fewer balance-related activities
      of daily life. DHI results showed that VV group expressed higher (p < 0.001) mean
      scores for self-perceived feelings of dizziness and imbalance (54%), compared to
      the Vest (9%) and Cont groups (1%). CONCLUSIONS: Anxiety related to VV requires
      special attention when assessing and managing vestibulopathy, regardless of
      patient age. IMPLICATIONS FOR REHABILITATION: Anxiety is a characteristic of
      subjects with visual vertigo (VV) and vestibulopathy. Anxiety in subjects with VV
      is not related to age. VV should be considered when subjects with anxiety
      complain of imbalance. Anxiety and vestibulopathy are often interrelated and
      should be considered in diagnostic evaluations.

PMID- 25597836
TI  - The syndemic illness of HIV and trauma: implications for a trauma-informed model
      of care.
AB  - BACKGROUND: People living with HIV infection are disproportionately burdened by
      trauma and the resultant negative health consequences, making the combination of
      HIV infection and trauma a syndemic illness. Despite the high co-occurrence and
      negative influence on health, trauma and posttraumatic sequelae in people living
      with HIV infection often go unrecognized and untreated because of the current
      gaps in medical training and lack of practice guidelines. OBJECTIVE: We set out
      to review the current literature on HIV infection and trauma and propose a trauma
      informed model of care to target this syndemic illness. METHODS: We searched
      PubMed, PsycINFO, and Cochrane review databases for articles that contained the
      following search terms: HIV AND either trauma (specifically violent trauma),
      PTSD, intimate partner violence (IPV), abuse, or trauma-informed care. Articles
      were limited to primary clinical research or metanalyses published in English.
      Articles were excluded if they referred to HIV-associated posttraumatic stress
      disorder or HIV-associated posttraumatic growth. RESULTS: We confirm high, but
      variable, rates of trauma in people living with HIV infection demonstrated in
      multiple studies, ranging from 10%-90%. Trauma is associated with (1) increased
      HIV-risk behavior, contributing to transmission and acquisition of the virus; (2)
      negative internal and external mediators also associated with poor health and
      high-risk HIV behavior; (3) poor adherence to treatment; (4) poor HIV-related and
      other health outcomes; and (5) particularly vulnerable special populations.
      CONCLUSIONS: Clinicians should consider using a model of trauma-informed care in
      the treatment of people living with HIV infection. Its adoption in different
      settings needs to be matched to available resources.

PMID- 25597837
TI  - Incidence of late-onset ocular hypertension following uncomplicated pars plana
      vitrectomy in pseudophakic eyes.
AB  - PURPOSE: To determine the incidence of late-onset ocular hypertension following
      uncomplicated vitrectomy in pseudophakic eyes with an open angle. DESIGN: A
      retrospective observational case series. METHODS: Seven hundred and sixty-seven
      eyes of 767 patients that underwent vitrectomy combined with cataract surgery in
      1 eye were studied. There were 383 men and 384 women. The indications for
      vitrectomy were: 308 eyes with rhegmatogenous retinal detachment, 202 eyes with
      epiretinal membrane, 169 eyes with macular hole, 44 eyes with vitreous
      hemorrhage, 16 eyes with subretinal hemorrhage, 15 eyes with vitreomacular
      traction syndrome, 12 eyes with vitreous opacity, and 1 eye with retinoschisis.
      Of these, 176 eyes underwent vitrectomy alone because of previous cataract
      surgery. Late-onset ocular hypertension was defined as an intraocular pressure
      (IOP) >21 mm Hg that developed more than 2 months postoperatively in at least 2
      postoperative visits. An increase in the IOP >4 mm Hg over the preoperative IOP
      was necessary. Eyes with ocular hypertension, glaucoma (suspect), or a
      possibility of IOP elevation were excluded. RESULTS: The mean age was 63 +/- 11
      years. The mean follow-up duration after vitrectomy was 47.8 +/- 25.3 months.
      Thirty-two eyes (4.2%) developed late-onset ocular hypertension. The mean age was
      60 +/- 10 years. The mean interval between vitrectomy and development of ocular
      hypertension was 31.1 +/- 26.0 months. There were no significant differences in
      the incidence of late-onset ocular hypertension and the vitreoretinal disease for
      vitrectomy, sex, or gauge of instruments for vitrectomy. CONCLUSION: Long-term
      IOP monitoring is necessary after vitrectomy.

PMID- 25597838
TI  - Association between statin use and uveitis: results from the Pacific Ocular
      Inflammation study.
AB  - PURPOSE: To assess whether there is a protective association between statin use
      and uveitis diagnosis. DESIGN: Retrospective, population-based case-control
      study. METHODS: Medical records of all patients in the Kaiser Permanente Hawaii
      health plan between January 1, 2006 and December 31, 2007 (N = 217 061) were
      searched electronically for International Classification of Diseases, 9th
      Revision, diagnosis codes related to uveitis. Chart review was done to confirm
      incident uveitis diagnosis during the study period. Two control groups were each
      randomly selected at a 5:1 ratio to cases, and controls were assigned an index
      date to match their respective case diagnosis date. One control group was
      selected from the general Kaiser Permanente Hawaii population that had at least 1
      healthcare visit during the study period. Another control group was selected from
      the population of Kaiser Permanente Hawaii members who had at least 1 visit to
      the ophthalmology clinic during the study period. Statin use was defined as
      filling a prescription for statin medication in the year prior to the diagnosis
      or index date based on an electronic search of the Kaiser Permanente Hawaii
      pharmacy database for Generic Product Identification codes. A conditional
      logistic regression model with clinical diagnosis of uveitis as the outcome was
      used to assess the relationship between statin use and uveitis. RESULTS: One
      hundred eight incident cases of uveitis were identified. Nineteen percent of
      uveitis patients had used statin medication in the year prior to diagnosis
      compared to 30% of patients in the general Kaiser population control (P = .03)
      and 38% of patients in the ophthalmology clinic control (P < .001). Using the
      general Kaiser population control and adjusting for age, sex, race, and
      autoimmune diseases, the odds of a statin user developing uveitis were 48% less
      than the odds of a non-statin user developing uveitis (OR: 0.52, 95% CI: 0.29
      0.94, P = .03). Similarly, the odds of developing uveitis were 33% less for
      statin users compared to non-statin users (OR: 0.67, 95% CI: 0.38-1.19, P = .17)
      when adjusting for these factors and using the ophthalmology clinic control
      group. CONCLUSIONS: Statin use may be protective against the development of
      uveitis. Several anti-inflammatory and immunomodulatory mechanisms may explain
      this association.

PMID- 25597841
TI  - High osmolarity glycerol response PtcB phosphatase is important for Aspergillus
      fumigatus virulence.
AB  - Aspergillus fumigatus is a fungal pathogen that is capable of adapting to
      different host niches and to avoid host defenses. An enhanced understanding of
      how, and which, A. fumigatus signal transduction pathways are engaged in the
      regulation of these processes is essential for the development of improved
      disease control strategies. Protein phosphatases are central to numerous signal
      transduction pathways. To comprehend the functions of protein phosphatases in A.
      fumigatus, 32 phosphatase catalytic subunit encoding genes were identified. We
      have recognized PtcB as one of the phosphatases involved in the high osmolarity
      glycerol response (HOG) pathway. The DeltaptcB mutant has both increased
      phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes.
      The DeltaptcB strain was more sensitive to cell wall damaging agents, had
      increased chitin and beta-1,3-glucan, and impaired biofilm formation. The
      DeltaptcB strain was avirulent in a murine model of invasive pulmonary
      aspergillosis. These results stress the importance of the HOG pathway in the
      regulation of pathogenicity determinants and virulence in A. fumigatus. 

PMID- 25597842
TI  - Effects of aging and maternal protein restriction on the muscle fibers morphology
      and neuromuscular junctions of rats after nutritional recovery.
AB  - Changes in the nutritional status of mothers may predispose their offspring to
      neuromuscular disorders in the long term. This study evaluated the effects of
      maternal protein restriction during pregnancy and lactation on the muscle fibers
      and neuromuscular junctions (NMJs) of the soleus muscle in the offspring of rats
      at 365 days of age that had undergone nutritional recovery. Wistar rats were
      divided into two groups: control (CG)--the offspring of mothers fed a normal
      protein diet (17%) and restricted (RG)--offspring of mothers fed a low protein
      diet (6%). After lactation, the male pups received standard chow ad libitum. At
      365 days, samples of soleus muscle were collected for muscle fiber analysis (HE
      staining, NADH-TR reaction and ultrastructure), intramuscular collagen
      quantification (picrosirius red staining) and NMJs analysis (non-specific
      esterase technique). The cross-sectional area of type I fibers was reduced by 20%
      and type IIa fibers by 5% while type IIb fibers increased by 5% in the RG
      compared to the CG. The percentage of intramuscular collagen was 19% lower in the
      RG. Disorganization of the myofibrils and Z line was observed, with the presence
      of clusters of mitochondria in both groups. Regarding the NMJs, in the RG there
      was a reduction of 10% in the area and 17% in the small diameter and an increase
      of 7% in the large diameter. The results indicate that the effects of maternal
      protein restriction on muscle fibers and NMJs seem to be long-lasting and
      irreversible.

PMID- 25597839
TI  - The African Descent and Glaucoma Evaluation Study (ADAGES): predictors of visual
      field damage in glaucoma suspects.
AB  - PURPOSE: To evaluate racial differences in the development of visual field (VF)
      damage in glaucoma suspects. DESIGN: Prospective, observational cohort study.
      METHODS: Six hundred thirty-six eyes from 357 glaucoma suspects with normal VF at
      baseline were included from the multicenter African Descent and Glaucoma
      Evaluation Study (ADAGES). Racial differences in the development of VF damage
      were examined using multivariable Cox proportional hazard models. RESULTS: Thirty
      one of 122 African-descent participants (25.4%) and 47 of 235 European-descent
      participants (20.0%) developed VF damage (P = .078). In multivariable analysis,
      worse baseline VF mean deviation, higher mean arterial pressure during follow-up,
      and a race * mean intraocular pressure (IOP) interaction term were significantly
      associated with the development of VF damage, suggesting that racial differences
      in the risk of VF damage varied by IOP. At higher mean IOP levels, race was
      predictive of the development of VF damage even after adjusting for potentially
      confounding factors. At mean IOPs during follow-up of 22, 24, and 26 mm Hg,
      multivariable hazard ratios (95% confidence intervals) for the development of VF
      damage in African-descent compared to European-descent subjects were 2.03 (1.15
      3.57), 2.71 (1.39-5.29), and 3.61 (1.61-8.08), respectively. However, at lower
      mean IOP levels (below 22 mm Hg) during follow-up, African descent was not
      predictive of the development of VF damage. CONCLUSION: In this cohort of
      glaucoma suspects with similar access to treatment, multivariate analysis
      revealed that at higher mean IOP during follow-up, individuals of African descent
      were more likely to develop VF damage than individuals of European descent.

PMID- 25597840
TI  - Diet in the pathogenesis and treatment of inflammatory bowel diseases.
AB  - Some of the most common symptoms of the inflammatory bowel diseases (IBD, which
      include ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea, and
      weight loss. It is therefore not surprising that clinicians and patients have
      wondered whether dietary patterns influence the onset or course of IBD. The
      question of what to eat is among the most commonly asked by patients, and among
      the most difficult to answer for clinicians. There are substantial variations in
      dietary behaviors of patients and recommendations for them, although clinicians
      do not routinely endorse specific diets for patients with IBD. Dietary clinical
      trials have been limited by their inability to include a placebo control,
      contamination of study groups, and inclusion of patients receiving medical
      therapies. Additional challenges include accuracy of information on dietary
      intake, complex interactions between foods consumed, and differences in food
      metabolism among individuals. We review the roles of diet in the etiology and
      management of IBD based on plausible mechanisms and clinical evidence.
      Researchers have learned much about the effects of diet on the mucosal immune
      system, epithelial function, and the intestinal microbiome; these findings could
      have significant practical implications. Controlled studies of patients receiving
      enteral nutrition and observations made from patients on exclusion diets have
      shown that components of whole foods can have deleterious effects for patients
      with IBD. Additionally, studies in animal models suggested that certain nutrients
      can reduce intestinal inflammation. In the future, engineered diets that restrict
      deleterious components but supplement beneficial nutrients could be used to
      modify the luminal intestinal environment of patients with IBD; these might be
      used alone or in combination with immunosuppressive agents, or as salvage therapy
      for patients who do not respond or lose responsiveness to medical therapies.
      Stricter diets might be required to induce remission, and more sustainable
      exclusion diets could be used to maintain long-term remission. 

PMID- 25597843
TI  - Polio endgame: the global introduction of inactivated polio vaccine.
AB  - In 2013, the World Health Assembly endorsed a plan that calls for the ultimate
      withdrawal of oral polio vaccines (OPV) from all immunization programs globally.
      The withdrawal would begin in a phased manner with removal of the type 2
      component of OPV in 2016 through a global switch from trivalent OPV to bivalent
      OPV (containing only types 1 and 3). To mitigate risks associated with immunity
      gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has
      recommended that all 126 OPV-only using countries introduce at least one dose of
      inactivated polio vaccine into routine immunization programs by end-2015, before
      the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio
      vaccine would reduce risks of reintroduction of type 2 poliovirus by providing
      some level of seroprotection, facilitating interruption of transmission if
      outbreaks occur, and accelerating eradication by boosting immunity to types 1 and
      3 polioviruses. 

PMID- 25597845
TI  - Family factors as moderators of link between reinforcement sensitivity and child
      and adolescent problem behaviour.
AB  - Moderating effects of family factors on the association between children's
      reinforcement sensitivity and problem behaviour have been examined in a community
      sample of 533 children aged from 3 to 17 years. Family type and living in urban
      areas exacerbated the effect of sensitivity to reward on externalizing,
      internalizing and impact of problems on everyday life; a high level of the
      father's education exacerbated the effect of sensitivity to reward on
      externalizing; family aggression and harsh parenting were found to strengthen the
      link between sensitivity to reward and the impact of problems on everyday life,
      whereas family cohesion buffered the negative effect of sensitivity to reward on
      externalizing and the impact of problems in everyday life.

PMID- 25597846
TI  - Radial nerve measurements in nonsymptomatic upper extremities of Filipinos: A
      cross-sectional study.
AB  - INTRODUCTION: Despite reports on the association of radial nerve (RN) size and
      lateral epicondylalgia (LE), Filipino normative values on RN size in healthy
      elbows are not established. An association with upper extremity anthropometric
      measurements is likewise not reported. METHODS: Musculoskeletal ultrasound
      measurements of the RN at the level of the lateral epicondyle (RN-LE), posterior
      interosseous nerve at the level of the radial head and supinator (PIN-RH and PIN
      sup), and superficial RN (SRN) in the elbows of healthy Filipinos were made in
      Manila from January-September 2011. RESULTS: A total of 198 elbows of 99 healthy
      participants aged 43 years (range, 33-48 years) [median(IQR)] were investigated.
      Men have larger PIN-RH, PIN-sup, and SRN compared with women. Arm length was
      associated with PIN-RH, PIN-sup, and SRN (P < 0.05). Activities and elbow
      circumference measurements (at 2 levels) were associated with PIN-RH.
      CONCLUSIONS: RN reference values can now be used for comparison in elbows with
      LE.

PMID- 25597847
TI  - Regular atrial tachycardias following pulmonary vein isolation for paroxysmal
      atrial fibrillation: a retrospective comparison between the cryoballoon and
      conventional focal tip radiofrequency techniques.
AB  - PURPOSE: Occurrence of atrial tachycardias (ATs) following radiofrequency (RF)
      pulmonary vein (PV) isolation for the treatment of paroxysmal atrial fibrillation
      (PAF) is a frequent complication. Cryoballoon (CB) ablation might create more
      homogeneous and demarcated lesions than traditional point by point RF approach,
      hypothetically leading to a lower incidence of ATs. Our aim is to compare
      incidence and mechanism of regular ATs occurring after ablation of PAF by means
      of circumferential point by point RF vs CB ablation. METHODS: Two hundred eighty
      six consecutive patients undergoing a first PV isolation procedure, as treatment
      for PAF, were included and followed up for 12 months. Point by point RF ablation
      was performed in 186 patients and CB ablation in the remaining 100. Among the
      last ones, first generation (CB-1) was used in 59 patients and second generation
      one (CB-2) in 41. RESULTS: Incidence of regular ATs was higher following RF PV
      isolation when compared with CB ablation (11.3 vs 3.0%, P = 0.028). When compared
      separately with RF ablation, both CB-1 and CB-2 presented lower incidences of ATs
      (5.1 and 0.0%) but differences only remained significant for the CB-2 (P =
      0.027). CONCLUSION: Patients with PAF undergoing a first PV isolation procedure
      by means of CB ablation present a significantly lower incidence of ATs than those
      in which PV isolation is achieved by means of circumferential point by point RF
      ablation.

PMID- 25597848
TI  - Donor age and operational tolerance in living donor liver transplantation.

PMID- 25597849
TI  - Investigating the formal countermeasures and informal strategies used to mitigate
      SPAD risk in train driving.
AB  - Various countermeasures are used to mitigate signal passed at danger (SPAD)
      events on railways, yet they continue. While risk factors that destabilise
      cognitive processes have been identified, less has been published on the
      relationship between these factors and the informal strategies that drivers
      themselves adopt to reduce individual SPAD risk. This study aimed to address this
      gap and used a participative approach to collect and thematically analyse data
      from 28 drivers across eight rail organisations in Australia and New Zealand. The
      results showed not all formal countermeasures were considered effective, and
      identified several informal strategies. These aimed to reduce task disruption,
      service distortion and maintain connectedness to signals. While some evidenced
      redundancies in the task and cab, others did not reduce baseline risk. This paper
      explores the relationship between the established risks and identified strategies
      towards evaluating the utility of formal and informal mitigations. The research
      has application to the investigation of collision risk in all transport domains.
      Practitioner Summary: A participative approach was used to investigate SPAD
      mitigation techniques in train driving, and to explore risk-strategy relationship
      dynamics. Several informal strategies designed to reduce task disruption, service
      distortion and maintain signal connectedness were identified. While some
      evidenced redundancies in the task and cab, others did not reduce baseline risk. 

PMID- 25597830
TI  - Biological interpretation of genome-wide association studies using predicted gene
      functions.
AB  - The main challenge for gaining biological insights from genetic associations is
      identifying which genes and pathways explain the associations. Here we present
      DEPICT, an integrative tool that employs predicted gene functions to
      systematically prioritize the most likely causal genes at associated loci,
      highlight enriched pathways and identify tissues/cell types where genes from
      associated loci are highly expressed. DEPICT is not limited to genes with
      established functions and prioritizes relevant gene sets for many phenotypes. 

PMID- 25597850
TI  - Highly enantioselective nickel-catalyzed intramolecular reductive cyclization of
      alkynones.
AB  - The first asymmetric nickel-catalyzed intramolecular reductive cyclization of
      alkynones is reported. A P-chiral monophosphine and triethylsilane were used as
      the ligand and the reducing reagent, respectively, to form a series of tertiary
      allylic alcohols bearing furan/pyran rings in excellent yields and
      enantioselectivities. This reaction has a broad substrate scope and enabled the
      efficient synthesis of dehydroxycubebin and chiral dibenzocyclooctadiene
      skeletons. 

PMID- 25597851
TI  - Dipeptidyl peptidase-4 greatly contributes to the hydrolysis of vildagliptin in
      human liver.
AB  - The major metabolic pathway of vildagliptin in mice, rats, dogs, and humans is
      hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7
      (LAY151), whereas the major metabolic enzyme of vildagliptin has not been
      identified. In the present study, we determined the contribution rate of
      dipeptidyl peptidase-4 (DPP-4) to the hydrolysis of vildagliptin in the liver. We
      performed hydrolysis assay of the cyano group of vildagliptin using mouse, rat,
      and human liver samples. Additionally, DPP-4 activities in each liver sample were
      assessed by DPP-4 activity assay using the synthetic substrate H-glycyl-prolyl-7
      amino-4-methylcoumarin (Gly-Pro-AMC). M20.7 formation rates in liver microsomes
      were higher than those in liver cytosol. M20.7 formation rate was significantly
      positively correlated with the DPP-4 activity using Gly-Pro-AMC in liver samples
      (r = 0.917, P < 0.01). The formation of M20.7 in mouse, rat, and human liver S9
      fraction was inhibited by sitagliptin, a selective DPP-4 inhibitor. These
      findings indicate that DPP-4 is greatly involved in vildagliptin hydrolysis in
      the liver. Additionally, we established stable single expression systems of human
      DPP-4 and its R623Q mutant, which is the nonsynonymous single-nucleotide
      polymorphism of human DPP-4, in human embryonic kidney 293 (HEK293) cells to
      investigate the effect of R623Q mutant on vildagliptin-hydrolyzing activity.
      M20.7 formation rate in HEK293 cells expressing human DPP-4 was significantly
      higher than that in control HEK293 cells. Interestingly, R623Q mutation resulted
      in a decrease of the vildagliptin-hydrolyzing activity. Our findings might be
      useful for the prediction of interindividual variability in vildagliptin
      pharmacokinetics. 

PMID- 25597852
TI  - Cortical surface area and thickness in adult survivors of pediatric acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Advances in the treatment of acute lymphoblastic leukemia (ALL) have
      led to great improvements in survival rates and outcomes, but there is concern
      about cognitive late effects. We aimed to determine whether ALL survivors have
      smaller cortical surface area and/or thickness, and test whether this is related
      to disease and treatment variables and self-reported executive functioning in
      everyday life. PROCEDURE: Magnetic resonance imaging (MRI) scans from 130 adult
      long-term survivors of childhood ALL (age: 18-46 years; age at diagnosis: 0-16
      years; years since diagnosis: 7-40) and 130 healthy controls were assessed to
      estimate and compare regional cortical surface area and thickness. Information on
      disease and treatment factors were obtained from patients' records, and executive
      functioning in survivors was measured using a validated questionnaire (BRIEF-A).
      RESULTS: Smaller cortical surface area was observed in several regions in both
      cerebral hemispheres in ALL survivors. In these regions, mean surface area was
      4.1-5.5% smaller in ALL survivors compared to healthy controls. In contrast, only
      one region showed lower cortical thickness in ALL survivors. There were no
      significant associations between cortical surface area/thickness in these regions
      and disease or treatment variables. In ALL survivors, smaller surface area in
      prefrontal regions, encompassing parts of the superior frontal gyri and the left
      anterior cingulate cortex, was associated with problems in executive functioning,
      specifically with emotional control and self-monitoring. CONCLUSIONS: ALL
      survivors had smaller surface area in several cortical regions and smaller
      surface area in prefrontal regions was associated with reported problems in
      executive functioning.

PMID- 25597854
TI  - Role of oxidative stress in surgical cavernous nerve injury in a rat model.
AB  - This study investigates the role of oxidative stress in surgical cavernous nerve
      (CN) injury in a rat model. Eighty-four male Sprague-Dawley rats were randomly
      divided into three groups: group 1, sham-operated rats; group 2, bilateral CN
      crushed rats; and group 3, bilateral CN-transection-and-sutured-immediately rats.
      Oxidative stress was evaluated by malondialdehyde levels, super oxide dismutase
      (SOD) activities, and glutathione peroxidase (GPX) activities in serum. Erectile
      function was assessed by CN electrostimulation at 3 months with mean maximal
      intracavernous pressure (ICP) and maximal ICP per mean arterial pressure. Nerve
      injury was assessed by toluidine blue staining of CNs and nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. GPX protein
      expression and nitrotyrosine-3 (NT-3) levels in penile tissue were measured.
      Erectile function and the number of myelinated axons of CNs and NADPH-diaphorase
      positive nerve fibers were statistically decreased between groups, from sham to
      crush to transection. For markers, both nerve-injury groups showed increased
      oxidative stress markers at early time points, with the transection group showing
      greater oxidative stress than the crushed group and values normalizing to sham
      levels by week 12. GPX expression and NT-3 levels in penile tissue were in
      concordance with the results of SOD and GPX. These results show that oxidative
      stress plays an important role in injured CNs, and different methods of CN injury
      can lead to different degrees of oxidative stress in a rat model.

PMID- 25597855
TI  - Using hollow carbon nanospheres as a light-induced free radical generator to
      overcome chemotherapy resistance.
AB  - Under evolutionary pressure from chemotherapy, cancer cells develop resistance
      characteristics such as a low redox state, which eventually leads to treatment
      failures. An attractive option for combatting resistance is producing a high
      concentration of produced free radicals in situ. Here, we report the production
      and use of dispersible hollow carbon nanospheres (HCSs) as a novel platform for
      delivering the drug doxorubicine (DOX) and generating additional cellular
      reactive oxygen species using near-infrared laser irradiation. These irradiated
      HCSs catalyzed sufficiently persistent free radicals to produce a large number of
      heat shock factor-1 protein homotrimers, thereby suppressing the activation and
      function of resistance-related genes. Laser irradiation also promoted the release
      of DOX from lysosomal DOX@HCSs into the cytoplasm so that it could enter cell
      nuclei. As a result, DOX@HCSs reduced the resistance of human breast cancer cells
      (MCF-7/ADR) to DOX through the synergy among photothermal effects, increased
      generation of free radicals, and chemotherapy with the aid of laser irradiation.
      HCSs can provide a unique and versatile platform for combatting chemotherapy
      resistant cancer cells. These findings provide new clinical strategies and
      insights for the treatment of resistant cancers. 

PMID- 25597856
TI  - Nemaline myopathy and heart failure: role of ivabradine; a case report.
AB  - BACKGROUND: Nemaline myopathy (NM) is a rare congenital myopathy characterized by
      muscle weakness, hypotonia and the presence in muscle fibers of inclusions known
      as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from
      severe forms with neonatal onset to asymptomatic forms. The adult-onset form is
      heterogeneous in terms of clinical presentation and disease progression. Cardiac
      involvement occurs in the minority of cases and little is known about medical
      management in this subgroup of NM patients. We report a rare case of heart
      failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be
      able to dramatically improve the clinical picture. CASE PRESENTATION: We report a
      case of a 37-year-old man with adult-onset NM, presenting with weakness and
      hypotonia of the proximal limb muscles and shoulder girdle, severely limiting
      daily activities. He developed progressive HF over a period of 6 months while
      attending a rehabilitation program, with reduced left ventricular ejection
      fraction (LVEF = 20%), manifested by dyspnea and signs of systemic congestion.
      The patient was started HF therapy with enalapril, carvedilol, spironolactone and
      loop diuretics. Target HF doses of these drugs (including carvedilol) were not
      reached because of symptomatic hypotension causing a high resting heart rate (HR)
      >=70 beats per minute (bpm). Further deterioration of the clinical picture
      occurred with several life-threatening arrhythmic episodes requiring external
      defibrillation. An implantable cardioverter defibrillator (ICD) was then
      implanted. Persistent high resting HR was successfully treated with ivabradine
      with HR lowering from 90 bpm to 55 bpm at 1 month follow up, LVEF rising to 50%
      at 3 month follow up and to 54% at 2,5 year follow up. To date no more
      hospitalizations for heart failure occurred. A single hospitalization due to
      aspiration pneumonia required insertion of a tracheostomy tube to protect airways
      from further aspiration. At present, the patient is attending a regular
      rehabilitation program with net improvement in neuromotor control and less
      limitations in daily activities. CONCLUSIONS: HF is a rare feature of NM, but it
      can negatively influence prognosis. Conventional HF therapy and/or heart
      transplant are the only reasonable strategy in these patients. Ivabradine is a
      useful, effective and safe drug for therapy in NM patients with HF and should be
      considered when resting HR remains high despite beta-blockers' full titration or
      beta-blockers' underdosing due to intolerance or side effects.

PMID- 25597858
TI  - Association between the disability prevention program "Secondary Preventive
      Services" and disability incidence among the elderly population: A nationwide
      longitudinal comparison of Japanese municipalities.
AB  - AIM: The aim of the present ecological study was to evaluate the relationship
      between the rate of participation in Secondary Preventive Services (SPS) and the
      incidence of disability in Japanese municipalities. METHODS: We used the national
      statistics data for Long-term Care Insurance (LTCI), because all Japanese people
      aged >=65 years are eligible for LTCI services depending on their functional
      status assessed by a national uniform standard in all municipalities. The
      disability incidence rate for the 2-year period in 2009-2010 was compared among
      five different levels of SPS participation in 2006-2008. The primary outcome was
      the sum total disability incidence rate in LTCI from 2009 to 2010. The outcome
      was divided according to disability level into three patterns: "all levels
      (Support Level 1 - Care Level 5)", "mild disability (Care Level <=1)" and
      "moderate to severe disability (Care Level >=2)". RESULTS: There was a
      significant inverse association between the SPS participation rate and disability
      incidence rate. Among 1541 municipalities, those in the highest SPS participation
      rate quintile (>=9.79 per 1000 elderly population) had a lower disability
      incidence rate for all levels than those in the lowest quintile (<1.86 per 1000
      elderly population; absolute rate difference 0.6%; age-adjusted incident rate
      ratio 0.94; 95% CI 0.89-0.99). This inverse association was observed for mild
      disability and not for moderate to severe disability. CONCLUSIONS: Municipalities
      with a higher SPS participation rate have a lower incidence rate of mild
      disability. SPS could be an effective health policy for containing mild
      disability incidence among the elderly.

PMID- 25597857
TI  - Tuning LeSPL-CNR expression by SlymiR157 affects tomato fruit ripening.
AB  - In plants, microRNAs (miRNAs) play essential roles in growth, development, yield,
      stress response and interactions with pathogens. However no miRNA has been
      experimentally documented to be functionally involved in fruit ripening although
      many miRNAs have been profiled in fruits. Here we show that SlymiR157 and
      SlymiR156 differentially modulate ripening and softening in tomato (Solanum
      lycopersicum). SlymiR157 is expressed and developmentally regulated in normal
      tomato fruits and in those of the Colourless non-ripening (Cnr) epimutant. It
      regulates expression of the key ripening gene LeSPL-CNR in a likely dose
      dependent manner through miRNA-induced mRNA degradation and translation
      repression. Viral delivery of either pre-SlymiR157 or mature SlymiR157 results in
      delayed ripening. Furthermore, qRT-PCR profiling of key ripening regulatory genes
      indicates that the SlymiR157-target LeSPL-CNR may affect expression of LeMADS
      RIN, LeHB1, SlAP2a and SlTAGL1. However SlymiR156 does not affect the onset of
      ripening, but it impacts fruit softening after the red ripe stage. Our findings
      reveal that working together with a ripening network of transcription factors,
      SlymiR157 and SlymiR156 form a critical additional layer of regulatory control
      over the fruit ripening process in tomato. 

PMID- 25597859
TI  - S6 inhibition contributes to isoflurane neurotoxicity in the developing brain.
AB  - Postnatal isoflurane exposure leads to neurodegeneration and deficits of spatial
      learning and memory in the adulthood. However, the underlying mechanisms remain
      unclear. Ribosomal protein S6 is demonstrated to play a pivotal role in control
      of cell survival, protein synthesis and synaptogenesis for brain development. In
      this study, the possible role of S6 and its upstream signaling pathways in the
      developmental neurotoxicity of isoflurane was evaluated using models of primary
      cultured hippocampal neurons and postnatal day 7 rats. We found that isoflurane
      decreased IGF-1 level and suppressed activation of IGF-1 receptor, sequentially
      inhibiting S6 activity via IGF-1/MEK/ERK and IGF-1/PI3K/Akt signaling pathways.
      S6 inhibition enhanced isoflurane-induced decreased Bcl-xL and increased cleaved
      caspase-3 and Bad, also reduced PSD95 expression and aggravated deficits of
      spatial learning and memory. S6 activation could reverse the damages above. These
      results indicate that S6 inhibition, led by suppression of upstream IGF-1/MEK/ERK
      and IGF-1/PI3K/Akt signaling pathways, is involved in the neuroapoptosis,
      synaptogenesis impairment and spatial learning and memory decline caused by
      postnatal isoflurane exposure. S6 activation may exhibit protective potential
      against developmental neurotoxicity of isoflurane. 

PMID- 25597860
TI  - Human in vivo and in vitro studies on gastrointestinal absorption of titanium
      dioxide nanoparticles.
AB  - The study was designed to conduct human in vivo and in vitro studies on the
      gastrointestinal absorption of nanoparticles, using titanium dioxide as a model
      compound, and to compare nanoparticle behaviour with that of larger particles. A
      supplier's characterisation data may not fully describe a particle formulation.
      Most particles tested agreed with their supplied characterisation when assessed
      by particle number but significant proportions of 'nanoparticle formulations'
      were particles >100nm when assessed by particle weight. Oral doses are measured
      by weight and it is therefore important that the weight characterisation is taken
      into consideration. The human volunteer studies demonstrated that very little
      titanium dioxide is absorbed gastrointestinally after an oral challenge. There
      was no demonstrable difference in absorption for any of the three particle sizes
      tested. All tested formulations were shown to agglomerate in simulated gastric
      fluid, particularly in the smaller particle formulations. Further agglomeration
      was observed when dispersing formulations in polymeric or elemental foods.
      Virtually no translocation of titanium dioxide particles across the cell layer
      was demonstrated. This study found no evidence that nanoparticulate titanium
      dioxide is more likely to be absorbed in the gut than micron-sized particles. 

PMID- 25597861
TI  - Detoxification of organophosphorus pesticides and nerve agents through RSDL:
      efficacy evaluation by (31)P NMR spectroscopy.
AB  - Intoxication by organophosphorus compounds, especially by pesticides, poses a
      considerable risk to the affected individual. Countermeasures involve both
      medical intervention by means of antidotes as well as external decontamination to
      reduce the risk of dermal absorption. One of the few decontamination options
      available is Reactive Skin Decontamination Lotion (RSDL), which was originally
      developed for military use. Here, we present a (31)P NMR spectroscopy based
      methodology to evaluate the detoxification efficacy of RSDL with respect to a
      series of organophosphorus pesticides and nerve agents. Kinetic analysis of the
      obtained NMR data provided degradation half-lives proving that RSDL is also
      reasonably effective against organophosphorus pesticides. Unexpected observations
      of different RSDL degradation patterns are presented in view of its reported
      oximate-catalyzed mechanism of action. 

PMID- 25597862
TI  - Non-inferiority of silodosin 4 mg once daily to twice daily for storage symptoms
      score evaluated by the International Prostate Symptom Score in Japanese patients
      with benign prostatic hyperplasia: a multicenter, randomized, parallel-group
      study.
AB  - OBJECTIVES: To compare the effect of treatment with silodosin 4 mg once daily
      versus that of silodosin 4 mg twice daily on storage symptoms in Japanese
      patients with benign prostatic hyperplasia. METHODS: A prospective, multicenter,
      12-week, open-labeled study randomized a total of 268 men aged 50 years or older
      with benign prostatic hyperplasia and overactive bladder to silodosin 4 mg/day or
      8 mg/day. Changes in the end-points of the average value of International
      Prostate Symptom Score, quality of life index in the International Prostate
      Symptom Score, Overactive Bladder Symptom Score and urodynamic parameters were
      evaluated. The change in the storage symptom subtotal score of the International
      Prostate Symptom Score was considered as the primary end-point. RESULTS:
      Silodosin 4 mg/day was not inferior to silodosin 8 mg/day in regard to the
      primary end-point. In contrast, the efficacy of treatment with silodosin 4 mg
      twice daily was greater than that of 4 mg once daily, based on both the quality
      of life index and the Overactive Bladder Symptom Score total score. There was a
      discrepancy between the scores evaluated using the International Prostate Symptom
      Score and Overactive Bladder Symptom Score questionnaires. CONCLUSIONS: Silodosin
      4 mg once daily is not inferior to silodosin 4 mg twice daily in regard to
      storage symptoms score evaluated by the International Prostate Symptom Score. In
      contrast, silodosin 4 mg twice daily is more effective on storage symptoms
      evaluated by the Overactive Bladder Symptom Score than silodosin 4 mg once daily.

PMID- 25597863
TI  - The First Ten of Everything: A Review of Past and Current Practice in Pediatric
      Cardiac Percutaneous Interventions.
AB  - OBJECTIVES: This study was designed to compare outcomes of the most common
      pediatric cardiac interventions from the time of implementation with the current
      era. BACKGROUND: Since the introduction of semilunar valve balloon dilation and
      device closure of the arterial duct and septal defects, development of
      interventional techniques and devices has been rapid. However, few studies have
      compared outcomes between those initial interventions and those in the current
      era. METHODS: Five validated common catheter-based therapies were chosen for
      analysis, including atrial and duct device closure, balloon dilation of the
      aortic and pulmonary valves, and native coarctation of the aorta. A retrospective
      review of the first and most recent 10 consecutive patients in each group was
      performed. RESULTS: There was a high mortality (30%) among neonates who underwent
      aortic valve (AV) dilation in the early era, but no mortality noted in other
      groups. In the early era, transcatheter atrial defect closure and AV dilations
      were associated with a low success rate (60% for both lesions) and a high
      complication rate (40% for atrial septal defect, 30% for AV dilations). Among the
      last 10 children, the atrial defect occlusion was successful in 100% without
      complications and AV dilations where successful in all children with a 30%
      complication rate (one major, two minor). CONCLUSIONS: A learning curve with
      device development plays a significant role in the evolution of transcatheter
      techniques. These data provide baseline estimates of success and may be used as a
      template in the future when new techniques are adapted into practice.

PMID- 25597864
TI  - An ignored variable: solution preparation temperature in protein crystallization.
AB  - Protein crystallization is affected by many parameters, among which certain
      parameters have not been well controlled. The temperature at which the protein
      and precipitant solutions are mixed (i.e., the ambient temperature during mixing)
      is such a parameter that is typically not well controlled and is often ignored.
      In this paper, we show that this temperature can influence protein
      crystallization. The experimental results showed that both higher and lower
      mixing temperatures can enhance the success of crystallization, which follows a
      parabolic curve with an increasing ambient temperature. This work illustrates
      that the crystallization solution preparation temperature is also an important
      parameter for protein crystallization. Uncontrolled or poorly controlled room
      temperature may yield poor reproducibility in protein crystallization. 

PMID- 25597865
TI  - Periodic artifact reduction in Fourier transforms of full field atomic resolution
      images.
AB  - The discrete Fourier transform is among the most routine tools used in high
      resolution scanning/transmission electron microscopy (S/TEM). However, when
      calculating a Fourier transform, periodic boundary conditions are imposed and
      sharp discontinuities between the edges of an image cause a cross patterned
      artifact along the reciprocal space axes. This artifact can interfere with the
      analysis of reciprocal lattice peaks of an atomic resolution image. Here we
      demonstrate that the recently developed Periodic Plus Smooth Decomposition
      technique provides a simple, efficient method for reliable removal of artifacts
      caused by edge discontinuities. In this method, edge artifacts are reduced by
      subtracting a smooth background that solves Poisson's equation with boundary
      conditions set by the image's edges. Unlike the traditional windowed Fourier
      transforms, Periodic Plus Smooth Decomposition maintains sharp reciprocal lattice
      peaks from the image's entire field of view. 

PMID- 25597866
TI  - Ochratoxin A as possible factor trigging autism and its male prevalence via
      epigenetic mechanism.
AB  - The role of dysbiosis causing leaky gut with xenobiotic production and absorption
      is increasingly demonstrated in autism spectrum disorder (ASD) pathogenesis.
      Among xenobiotics, we focused on ochratoxin A (one of the major food
      contaminating mycotoxin), that in vitro and in vivo exerts a male-specific
      neurotoxicity probably via microRNA modulation of a specific target gene. Among
      possible targets, we focused on neuroligin4X. Interestingly, this gene carries
      some single nucleotide polymorphisms (SNPs) already correlated with the disease
      and with illegitimate microRNA binding sites and, being located on X-chromosome,
      could explain the male prevalence. In conclusion, we propose a possible gene
      environment interaction triggering ASD explaining the epigenetic neurotoxic
      mechanism activated by ochratoxin A in genetically predisposed children. This
      mechanism offers a clue for male prevalence of the disease and may have an
      important impact on prevention and cure of ASD.

PMID- 25597867
TI  - Severe left diaphragmatic hernia limits size of fetal left heart more than does
      right diaphragmatic hernia.
AB  - OBJECTIVES: To assess whether severity of congenital diaphragmatic hernia (CDH)
      correlates with the degree of left heart hypoplasia and left ventricle (LV)
      output, and to determine if factors leading to abnormal fetal hemodynamics, such
      as compression and reduced LV preload, contribute to left heart hypoplasia.
      METHODS: This was a retrospective cross-sectional study of fetuses at 16-37
      weeks' gestation that were diagnosed with CDH between 2000 and 2010. Lung-to-head
      ratio (LHR), liver position and side of the hernia were determined from stored
      ultrasound images. CDH severity was dichotomized based on LHR and liver position.
      The dimensions of mitral (MV) and aortic (AV) valves and LV were measured, and
      right and left ventricular outputs were recorded. RESULTS: In total, 188 fetuses
      with CDH were included in the study, 171 with left CDH and 17 with right CDH.
      Fetuses with severe left CDH had a smaller MV (Z = -2.24 +/- 1.3 vs -1.33 +/-
      1.08), AV (Z = -1.39 +/- 1.21 vs -0.51 +/- 1.05) and LV volume (Z = -4.23 +/- 
      2.71 vs -2.08 +/- 3.15) and had lower LV output (26 +/- 10% vs 32 +/- 10%) than
      those with mild CDH. MV and AV in fetuses with right CDH (MV, Z = -0.83 +/- 1.19
      and AV, Z = -0.71 +/- 1.07) were larger than those in fetuses with left CDH, but
      LV outputs were similarly diminished, regardless of hernia side. Severe
      dextroposition and abnormal liver position were associated independently with
      smaller left heart, while LHR was not. CONCLUSION: The severity of left heart
      hypoplasia correlates with the severity of CDH. Altered fetal hemodynamics,
      leading to decreased LV output, occurs in both right- and left-sided CDH, but the
      additional compressive effect on the left heart is seen only when the hernia is
      left-sided. Improved knowledge of the physiology of this disease may lead to
      advances in therapy and better risk assessment for use in counseling affected
      families.

PMID- 25597868
TI  - Ventricular interdependence in pulmonary arterial hypertension: providing small
      pieces of a complex puzzle.

PMID- 25597869
TI  - Steps forward in regulatory pathways for acute and chronic heart failure.
AB  - A workshop was organized by the Agenzia Italiana del Farmaco (AIFA) to discuss
      unmet needs and ways forward in the development of medicines in heart failure,
      their rationale, and cost-effective use. An integrated, multidisciplinary
      approach, including patients' needs and perspectives, was advocated by all the
      participants as the way to the most effective treatment regimens. More work is
      needed for reaching consensus on clinical and functional endpoints, for
      validating patient reported outcomes and measurements of well-being. Similarly,
      the integration into the clinical programmes of the health technology
      assessment/payers perspective, in particular, the evaluation of 'real-life'
      treatment effectiveness and of health as a value, would help in shifting the
      development and authorization of medicines from the molecule paradigm to their
      evaluation in the context of the whole health care regimen. Through this kind of
      workshop, AIFA is trying to build a template for meetings devoted to debate unmet
      needs with all stakeholders towards tentative road maps for the future. 

PMID- 25597871
TI  - Erratum.

PMID- 25597870
TI  - Clinical profile and prognostic significance of natriuretic peptide trajectory
      following hospitalization for worsening chronic heart failure: findings from the
      ASTRONAUT trial.
AB  - AIMS: The purpose of this study was to determine the prognostic significance and
      associated clinical profile of early post-discharge N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) trajectory among patients hospitalized for
      worsening chronic heart failure (HHF). METHODS AND RESULTS: This post-hoc
      analysis of the Aliskiren Trial in Acute Heart Failure Outcomes (ASTRONAUT)
      included 1351 HHF patients with ejection fraction (EF) <=40%, elevated B-type
      natriuretic peptide >=400 pg/mL or NT-proBNP >=1600 pg/mL at admission, and
      available NT-proBNP measurements (from a central core laboratory) at baseline
      (median 5 days after admission) and 1-month follow-up. The co-primary endpoints
      were all-cause mortality and cardiovascular mortality or HHF within 12 months.
      Median follow-up was 11.3 months. Patients with decreasing post-discharge NT
      proBNP trajectory tended to be younger and have non-ischaemic HF aetiology. The
      presence of baseline atrial fibrillation was associated with high NT-proBNP at 1
      month (i.e. above the median), regardless of the baseline value. After adjustment
      for patient characteristics and 1-month NT-proBNP level, every twofold increase
      in continuous NT-proBNP change from baseline to 1 month was predictive of
      increased cardiovascular mortality or HHF (hazard ratio 1.14; 95% confidence
      interval 1.02-1.26), but not all-cause mortality (hazard ratio 0.95; 95%
      confidence interval 0.81-1.11). CONCLUSION: In this cohort of HHF patients with
      reduced EF, early post-discharge NT-proBNP trajectory was associated with a
      distinct clinical profile and carried independent prognostic value after
      adjustment for patient characteristics and absolute NT-proBNP level. Future
      prospective study of serial NT-proBNP measurement during the hospital and early
      post-discharge periods is warranted to validate these findings and evaluate post
      discharge NT-proBNP trajectory as a therapeutic target.

PMID- 25597872
TI  - Versatile functionalization of carbon electrodes with a polypyridine ligand:
      metallation and electrocatalytic H(+) and CO2 reduction.
AB  - A strategy is proposed for immobilization of homogeneous catalysts whereby a
      glassy carbon electrode is functionalized by electro-grafting of a ligand,
      terpyridine. The modified electrode can easily be metallated with cobalt and
      shows activity towards catalytic proton and CO2 reduction. The metal can be
      removed and the electrode re-metallated at will. 

PMID- 25597873
TI  - Fungal oxalate decarboxylase activity contributes to Sclerotinia sclerotiorum
      early infection by affecting both compound appressoria development and function.
AB  - Sclerotinia sclerotiorum pathogenesis requires the accumulation of high levels of
      oxalic acid (OA). To better understand the factors affecting OA accumulation, two
      putative oxalate decarboxylase (OxDC) genes (Ss-odc1 and Ss-odc2) were
      characterized. Ss-odc1 transcripts exhibited significant accumulation in
      vegetative hyphae, apothecia, early stages of compound appressorium development
      and during plant colonization. Ss-odc2 transcripts, in contrast, accumulated
      significantly only during mid to late stages of compound appressorium
      development. Neither gene was induced by low pH or exogenous OA in vegetative
      hyphae. A loss-of-function mutant for Ss-odc1 (Deltass-odc1) showed wild-type
      growth, morphogenesis and virulence, and was not characterized further. Deltass
      odc2 mutants hyperaccumulated OA in vitro, were less efficient at compound
      appressorium differentiation and exhibited a virulence defect which could be
      fully bypassed by wounding the host plant prior to inoculation. All Deltass-odc2
      phenotypes were restored to the wild-type by ectopic complementation. An S.
      sclerotiorum strain overexpressing Ss-odc2 exhibited strong OxDC, but no oxalate
      oxidase activity. Increasing inoculum nutrient levels increased compound
      appressorium development, but not penetration efficiency, of Deltass-odc2
      mutants. Together, these results demonstrate differing roles for S. sclerotiorum
      OxDCs, with Odc2 playing a significant role in host infection related to compound
      appressorium formation and function. 

PMID- 25597875
TI  - (Epi)genomics approaches and their applications.

PMID- 25597874
TI  - The g.841G>C SNP of FASN gene is associated with fatty acid composition in beef
      cattle.
AB  - The objective of the current study is to evaluate the association between fatty
      acid composition and fatty acid synthase gene polymorphisms as responsible
      mutations. For this purpose, we selected seven previously reported single
      nucleotide polymorphisms (SNPs) in FASN gene, including one within promoter
      region (g.841G>C) and six non-synonymous SNPs (g.8805C>T, g.13126C>T, g.15532A>C,
      g.16024A>G, g.16039C>T, g.17924A>G), and genotyped them in Japanese Black cattle.
      Genotyping results revealed that g.8805 C>T and g.17924 A>G were monomorphic
      loci. Genome-wide association analysis including the other five SNPs revealed
      that only g.841G>C showed significant associations with the percentages of C14:0,
      C14:1, C16:1 and C18:1 at 5% genome-wide significance level. In order to further
      evaluate the effect, we genotyped g.841G>C using additional three populations,
      including two Japanese Black populations and a Holstein cattle population.
      g.16024A>G was also genotyped and included in the analysis because it has been
      reported to be associated with fatty acid composition in Japanese Black cattle.
      In the result of analysis of variance, g.841G>C showed stronger effects on fatty
      acid percentage than those of g.16024A>G in all populations. These results
      suggested that g.841G>C would be a responsible mutation for fatty acid
      composition and contribute to production of high-grade beef as a selection marker
      in beef cattle. 

PMID- 25597876
TI  - Immunohistochemical characterization of renal tumors in patients with Birt-Hogg
      Dube syndrome.
AB  - Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant disorder associated with a
      germline mutation of folliculin (FLCN). The affected families are at a high risk
      for developing multiple renal cell carcinomas (RCC). Little is known about the
      immunostaining patterns of mutant FLCN-associated RCCs. We investigated 32 RCCs
      obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n =
      15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n =
      3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1,
      Ksp-cadherin and CD82. They stained either focally or diffusely for CK7, and were
      negative for CA-IX. All clear cell RCCs were positively stained for CA-IX and
      negative for CK7. These data confirmed that mutant FLCN-associated oncocytic and
      clear cell RCCs exhibited generally similar immunostaining patterns compared to
      their sporadic counterparts. Frequent positive staining for S100A1, Ksp-cadherin
      and CD82 in chromophobe RCCs and HOCTs indicated that these two types were
      relatively similar rather than distinctively different in their patterns of
      immunoreactivity. Characteristic peri-nuclear halos and polygonal cells with
      clear cytoplasm, which often misleads pathologists into the diagnosis of clear
      cell RCC, should be carefully examined using an immunohistochemical panel
      including CA-IX, Ksp-cadherin, CD82 and CK7. 

PMID- 25597877
TI  - Clinical pharmacology of melatonin in the treatment of tinnitus: a review.
AB  - PURPOSE: We performed a review with the purpose to summarise, analyse and discuss
      the evidence provided by clinical studies evaluating effectiveness of melatonin
      in the cure of tinnitus. Due to the fact that there is no satisfactory treatment
      for tinnitus, clinical research has explored new therapeutic approaches. METHODS:
      A search of Pubmed, Medline, Embase, Central and Google Scholar was conducted to
      find trials published prior March 2014 on melatonin in the treatment of tinnitus.
      Design of the studies, randomization, allocation concealment procedures and
      diagnostic instruments (scales for tinnitus evaluation) were critical evaluated.
      RESULTS: Five clinical studies have been included. Three of them tested
      effectiveness of melatonin alone, the remaining two along with sulpiride and
      sulodexide respectively. Considered clinical trials adopted various experimental
      designs: single arm, randomised placebo-controlled and randomised placebo
      controlled followed by crossover. These studies were characterised by several
      methodological weaknesses. CONCLUSION: Confirmation of melatonin clinical
      effectiveness in the treatment of tinnitus cannot be given in the light of the
      biases observed in the considered evidence. Melatonin seems to improve sleep
      disturbance linked to tinnitus.

PMID- 25597878
TI  - Association between oral conditions and functional limitations in childhood.
AB  - The aim of this study was to evaluate the impact of oral conditions on functional
      limitations among preschoolers. A preschool-based, cross-sectional study was
      carried out with 843 preschoolers in Campina Grande, Brazil. Parents/caregivers
      answered a questionnaire addressing socio-demographic characteristics and
      perceptions regarding the general/oral health of their children as well as the
      Brazilian version of the Early Childhood Oral Health Impact Scale. The
      nonparametric Kruskal-Wallis test followed by Mann-Whitney test (alpha = 5%) was
      used to compare mean children's quality-of-life scores for each independent
      variable. Poisson regression analysis was used to test associations between the
      independent and dependent variables (difficulties eating, drinking and speaking)
      (alpha = 5%). The multivariate regression model involved a hierarchical approach
      with four levels (distal to proximal determinants): (i) socio-demographic
      aspects; (ii) health perceptions; (iii) oral conditions; and (iv) pain
      conditions. The prevalence of negative impact on function was 24.7% for
      eating/drinking and 8.0% for speaking. Significant associations were found
      between toothache and negative impact on eating/drinking (PR = 5.38; 95%CI: 3.20
      9.02) as well as between high severity dental caries and negative impact on
      speaking (PR = 14.91; 95%CI: 1.98-112.32). Dental caries, traumatic dental injury
      and malocclusion were not significantly associated with a negative impact on
      eating or drinking. However, toothache was an indicator of negative impact on
      eating/drinking and dental caries severity was an indicator of negative impact on
      speaking.

PMID- 25597879
TI  - Transforming growth factor-beta differently regulates urokinase type plasminogen
      activator and matrix metalloproteinase-9 expression in mouse macrophages;
      analysis of intracellular signal transduction.
AB  - Transforming growth factor beta (TGF-beta) modulates capacity of macrophages to
      produce urokinase type plasminogen activator (uPA) and matrix metalloproteinase-9
      (MMP9). uPA and MMP9 actively participate in extracellular matrix reorganization
      and influence macrophages chemotaxis and cell migration. Although, TGF-beta
      regulates uPA and MMP9 macrophages expression, the underlying intracellular
      signal mechanisms are not well elucidated so far. Here we have investigated the
      implication of TGF-beta signaling in the regulation of uPA and MMP9 expression in
      RAW 264.7 macrophages. The expression of uPA and MMP9 was assessed by zymography,
      Western blotting and RT-PCR. The involvement of Smad, MAPK or NFkappaB signaling
      pathways was evaluated by using specific inhibitors. Our results indicated that
      TGF-beta simultaneously increased uPA and reduced MMP9 expression. The Smad3,
      ERK1,2, and JNK1,2 signaling pathways seem to be the main mechanisms that mediate
      TGF-beta-induced uPA expression. Whereas TGF-beta-reduced MMP9 expression appears
      to be regulated independently by JNK1,2 activation and by NFkappaB signaling
      inhibition. Thus, our results suggested that, in murine macrophages, TGF-beta
      differentially regulates uPA and MMP9 expressions through different intracellular
      signaling mechanisms. In addition, presented data may help in understanding the
      role of TGF-beta in macrophages proteases regulation in inflammatory diseases. 

PMID- 25597881
TI  - Accumulation of BRI2-BRICHOS ectodomain correlates with a decreased clearance of
      Abeta by insulin degrading enzyme (IDE) in Alzheimer's disease.
AB  - The precursor protein BRI2 that in its mutated form is associated with British
      and Danish dementia, can regulate critical processes involved in AD pathogenesis
      including not only the metabolism of amyloid precursor protein (APP) and
      formation of Abeta, but also the levels of secreted insulin degrading enzyme
      (IDE), an enzyme involved in Abeta clearance. We recently observed increased
      levels of a 45kDa BRI2 form as well as BRI2 ectodomain deposits in Abeta plaques
      in human AD hippocampus, which may affect BRI2 functional activity. Since BRI2
      regulated the levels of secreted IDE and subsequent degradation of Abeta in human
      cell culture models, we explored if BRI2 changes could affect the Abeta
      degradation capacity of IDE in human hippocampus (n=28). We observed that IDE is
      the main enzyme involved in Abeta degradation, and both IDE levels as well as
      Abeta degradation tend to be decreased in AD. Interestingly, the levels of the
      45kDa BRI2 form and BRI2 deposits in hippocampal tissue were inversely correlated
      with IDE protein levels (r=-0.52, p=0.005; r=-0.4, p=0.045) and IDE activity (r=
      0.5935, p=0.0004; r=-0.4, p=0.03). Taken together, the current results suggest a
      relationship between BRI2 protein changes, IDE activity and Abeta levels in human
      hippocampus. Thus, the formation and accumulation high of molecular weight BRI2
      forms observed in AD may impair IDE functioning and consequently lead to impaired
      Abeta clearance and to the accumulation of Abeta. 

PMID- 25597880
TI  - Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is
      associated with up-regulation of let-7 microRNA.
AB  - Cofilin-1, a non-muscle isoform of actin regulatory protein that belongs to the
      actin-depolymerizing factor (ADF)/cofilin family is known to affect cancer
      development. Previously, we found that over-expression of cofilin-1 suppressed
      the growth and invasion of human non-small cell lung cancer (NSCLC) cells in
      vitro. In this study, we further investigated whether over-expression of cofilin
      1 can suppress tumor growth in vivo, and performed a microRNA array analysis to
      better understand whether specific microRNA would be involved in this event. The
      results showed that over-expression of cofilin-1 suppressed NSCLC tumor growth
      using the xenograft tumor model with the non-invasive reporter gene imaging
      modalities. Additionally, cell motility and invasion were significantly
      suppressed by over-expressed cofilin-1, and down-regulation of matrix
      metalloproteinase (MMPs) -1 and -3 was concomitantly detected. According to the
      microRNA array analysis, the let-7 family, particularly let-7b and let-7e, were
      apparently up-regulated among 248 microRNAs that were affected after over
      expression of cofilin-1 up to 7 days. Knockdown of let-7b or let-7e using
      chemical locked nucleic acid (LNA) could recover the growth rate and the invasion
      of cofilin-1 over-expressing cells. Next, the expression of c-myc, LIN28 and
      Twist-1 proteins known to regulate let-7 were analyzed in cofilin-1 over
      expressing cells, and Twist-1 was significantly suppressed under this condition.
      Up-regulation of let-7 microRNA by over-expressed cofilin-1 could be eliminated
      by co-transfected Twist-1 cDNA. Taken together, current data suggest that let-7
      microRNA would be involved in over-expression of cofilin-1 mediated tumor
      suppression in vitro and in vivo.

PMID- 25597882
TI  - Altered topological organization of brain structural network in Chinese children
      with developmental dyslexia.
AB  - Increasing evidence indicates that developmental dyslexia (DD) is a
      "disconnection syndrome", and new probes of connectome were applied to
      investigate the "disconnection" in DD. However, there is a lack of brain
      connectome studies of Chinese dyslexics, who may have a different neural
      impairment pattern due to the logographic nature of Chinese. The aim of this
      study was to investigate the topological organization characteristics of the DD
      brain using a structural network based analysis on the volumetric covariance,
      which is a method with the advantage of reflecting brain developmental changes.
      Twenty-five children diagnosed with DD and twenty-five typically developing
      controls were included. The structural networks based on the pair-wise
      correlation of gray matter volume from 90 brain regions were constructed for the
      two groups and compared. Compared to controls, the structural network of dyslexic
      children exhibited significantly increased local efficiency combined with a
      tendency of decreased global efficiency and prolonged characteristic path length,
      thus reflecting a more locally specialized topological organization. Two brain
      areas showed significantly altered local regional network properties: the left
      precentral gyrus with increased bi, and the right Heschl's gyrus with decreased
      bi and ki. Moreover, a series of hub regions (especially the right fronto
      temporal regions) identified in the network of typically developing children were
      not presented in the brain of DD. To our knowledge, this is the first whole-brain
      structural network study on Chinese dyslexics. This study provides evidence of
      brain topological organization changes in Chinese children with DD, and thus may
      help shed light on its neurobiological basis. 

PMID- 25597883
TI  - A novel, intelligent, pressure-sensing colostomy plug for reducing fecal leakage.
AB  - This study aims to describe and report the effectiveness of a novel, pressure
      sensing colostomy plug for reducing fecal leakage. Nine miniature Tibetan pigs,
      aged 6-8 months, were given colostomies and divided into three groups (n = 3 each
      group). A novel pressure-sensing colostomy plug was placed in each pig and set to
      indicate when intestinal pressures of either 5, 10, or 15 mm Hg, respectively,
      were reached. When the pressure thresholds were reached, the animals' bowels were
      examined for the presence of stool and/or stomal leakage, and the data were
      recorded at weeks 1, 4, and 8 after surgery. The colostomy plug calibrated to 15
      mm Hg pressure demonstrated the greatest accuracy in predicting the presence of
      stool in the bowels of study animals, averaging >90% sensitivity. In general, the
      sensitivity for predicting the presence of stool did not vary significantly over
      time, though there was a slight increase in accuracy in the 5 mm Hg group at
      later time-points. The sensitivity for predicting stool in the bowel did not
      change significantly over time in any of the three groups. Stomal leakage was
      found to be inversely proportional to the pressure-sensor setting, in that the 15
      mm Hg group exhibited the greatest amount of leakage. This difference, however,
      was found to be significant only at week 1 postsurgery. The intelligent, pressure
      sensing colostomy plug was able to accurately predict the presence of stool in
      the bowel and maintain continence, allowing negligible leakage.

PMID- 25597884
TI  - Hysterosalpingo-contrast-sonography (HyCoSy) in the assessment of tubal patency
      in endometriosis patients.
AB  - OBJECTIVE: Tubal patency in women with endometriosis has traditionally been
      evaluated by laparoscopy. The aim of this study was to investigate the accuracy
      of hysterosalpingo-contrast-sonography (HyCoSy) in the assessment of tubal
      patency in these women. STUDY DESIGN: A retrospective study was conducted at
      Physiopathology of Human Reproduction Unit. Infertile women who underwent HyCoSy
      and then a laparoscopy (dye test) within 6 months from the HyCoSy were included.
      Tubal patency was assessed by HyCoSy and the findings were compared with the
      results of laparoscopy, which was considered the gold standard for assessment of
      tubal patency. Sensitivity, specificity, positive and negative predictive values
      (PPV, NPV) and positive and negative likelihood ratios (Lh+, Lh-) were calculated
      including the 95% confidence interval (CI). RESULTS: A total of 1452 women
      underwent HyCoSy and 126 of them received a laparoscopy within 6 months from the
      HyCoSy. Of the 126 women, 42 (33.3%) had a diagnosis of pelvic endometriosis and
      84 (66.7%) had no endometriosis. In the endometriosis population, HyCoSy showed a
      sensitivity, specificity, PPV, NPV, Lh+ and Lh- of 85% (95% CI 62-96), 93% (95%
      CI 82-97), 81% (95% CI 58-94), 94% (95% CI 84-98), 12.6 (95% CI 4.8-33) and 0.15
      (95% CI 0.05-0.4) respectively. In the non-endometriosis group, HyCoSy showed a
      sensitivity, specificity, PPV, NPV, LR+ and LR- of 85% (95% CI 65-95), 93% (95%
      CI 87-96), 71% (95% CI 53-85), 97% (95% CI 92-99), 13.2 (95% CI 6.9-25) and 0.15
      (95% CI 0.06-0.3) respectively. The diagnostic accuracy of HyCoSy was 91% in the
      endometriosis group and 92% in the non-endometriosis patients. CONCLUSIONS:
      HyCoSy showed high accuracy in evaluating tubal patency in infertile non
      endometriosis women and in those affected by endometriosis.

PMID- 25597885
TI  - The clinical, structural, and biological features of neovaginas: a comparison of
      the Frank and the McIndoe techniques.
AB  - OBJECTIVE: To compare two methods of neovagina construction, the Frank and
      McIndoe techniques, in terms of structural and biological aspects. STUDY DESIGN:
      A total of 55 subjects were included in this retrospective study: 43 underwent
      the Frank technique (FT) and 12 underwent the McIndoe technique (MT). A clinical
      evaluation and a comparison of the structural (color, shine, presence of hair,
      and histology) and biological (bacteriological, pH, and hormonal determinations)
      features were performed. Statistical analysis was performed using the Fisher and
      Mann-Whitney tests. RESULTS: The time to achieve a functional neovagina using the
      FT was longer than when using the MT (9.8+/-5.3 versus 5.8+/-2.9 months)
      (p=0.01). The neovaginal wall of the MT skin grafts was more rigid and drier, and
      it did not exhibit a shine in the way that the FT skin grafts did. The lining of
      the cavity formed by the FT in all subjects was similar to that of vaginal
      mucosa, whereas the lining formed by the MT persisted as a skin graft in 83.3% of
      the cases. The pH was lower for the FT (p<0.01), and Doderlein bacilli were
      present in 90% of the FT neovaginas but absent from the MT neovaginas. In the
      latter, flora with anaerobic bacteria was present. Hormonal cytology showed
      estrogen activity in 100% of the FT neovaginas, but there was no such activity in
      the MT neovaginas. CONCLUSIONS: Our data suggest that the FT may be clinically,
      structurally, and biologically superior to the MT for the creation of neovaginas
      and is also less costly.

PMID- 25597886
TI  - Preterm birth in singleton and multiple pregnancies: evaluation of costs and
      perinatal outcomes.
AB  - OBJECTIVE: To estimate costs of preterm birth in singleton and multiple
      pregnancies. STUDY DESIGN: Cost analysis based on data from a prospective cohort
      study and three multicentre randomised controlled trials (2006-2012) in a Dutch
      nationwide consortium for women's health research. Women with preterm birth
      before 37 completed weeks were included for analysis. Direct costs were estimated
      from a health care perspective, from delivery until discharge or decease of the
      neonates. Costs and adverse perinatal outcome per pregnancy were measured.
      Adverse perinatal outcome comprised both perinatal mortality and a composite of
      neonatal morbidity defined as chronic lung disease, intraventricular
      haemorrhage>=grade 2, periventricular leukomalacia>=grade 1, proven sepsis or
      necrotising enterocolitis. Using a moving average technique covering three weeks
      per measurement, costs and adverse perinatal outcome per woman delivering for
      every week between 24 and 37 weeks are reported. RESULTS: Data of 2802 women were
      available of whom 1503 (53.6%) had a preterm birth; 501 in 1090 singleton (46%)
      and 1002 in 1712 multiple pregnancies (58.5%). The most frequent perinatal
      outcomes were perinatal mortality, chronic lung disease and sepsis. For singleton
      pregnancies the peak of total costs was at 25 weeks (?88,052 per delivery),
      compared to 27 weeks for multiple pregnancies (?169,571 per delivery). The total
      costs declined rapidly with increasing duration of pregnancy. Major cost drivers
      were length of stay on the NICU and airway treatments. The peaks seen in costs
      paralleled with the prevalence of adverse perinatal outcome. CONCLUSIONS: These
      data can be used to elaborate on the impact of preterm birth in case only data
      are available on duration of pregnancy.

PMID- 25597887
TI  - Patients' adherence to aspects of haemodialysis regimens in tropical north
      Queensland, Australia.
AB  - BACKGROUND: Patients with end-stage kidney disease often have difficulty in
      adhering to aspects of their haemodialysis regimens. OBJECTIVES: This study aimed
      to quantify the number of patients who attended 100% of their scheduled
      haemodialysis sessions, and the number of patients who gained no more than one
      kilogram per day between dialysis sessions, over a three-month period. DESIGN:
      Retrospective chart audit PARTICIPANTS: Patients undergoing haemodialysis at an
      in-hospital centre in tropical Australia. METHODS: A renal nurse audited the 72
      charts pertaining to a 12-week period in 2013. RESULTS: Patients attended 90.1%
      of all scheduled dialysis sessions. Forty-one patients attended all sessions,
      with the remaining 31 missing at least one scheduled session. One patient missed
      16 scheduled sessions. The following were statistically less likely to attend all
      their scheduled sessions: Aboriginal and Torres Strait Islander patients;
      patients on a three times per week dialysis schedule; patients who had relocated
      from rural or regional towns and younger patients. The average daily weight gain
      ranged from 0.414 kg to 1.017 kg (mean = 0.885 kg). Younger patients were
      statistically less likely to adhere to fluid restrictions; patients without
      diabetes were more likely to adhere to the fluid allowances. CONCLUSIONS AND
      APPLICATIONS TO PRACTICE: Renal services need to assist patients to adhere to
      their regimens. Initially, this service will examine strategies to maximise the
      likelihood of patients attending all of their dialysis sessions. Such an outcome
      will help to delay deterioration in the patients' health status, while minimising
      additional strain on the health service.

PMID- 25597888
TI  - Simultaneous quantification of chrysophanol and physcion in rat plasma by ultra
      fast liquid chromatography-tandem mass spectrometry and application of the
      technique to comparative pharmacokinetic studies of Radix et Rhei Rhizoma extract
      alone and Dahuang Fuzi Decoction.
AB  - Most herbal medicines are prescribed in combination based on the theory of TCM to
      obtain synergistic effects or diminish the possible adverse reactions.
      Compatibility refers to the combination of two or more herbs based on the
      clinical settings and the properties of herbs. Chrysophanol and physcion are the
      main effective compounds in Radix et Rhizoma Rhei and Dahuang Fuzi Decoction
      which is the combination of Radix et Rhizoma Rhei, Radix Aconiti Lateralis
      Praeparata and Radix et Rhizoma Asari. However, chrysophanol and physcion are
      difficult to detect in vivo because of their low concentration and interference
      from endogenous compounds. The aim of this study is to develop a rapid, specific
      and sensitive ultra high performance liquid chromatography-triple quadrupole
      tandem mass method to simultaneously quantify chrysophanol and physcion in rat
      plasma, in order to better understand the pharmacokinetics and compatibility
      mechanism of Dahuang Fuzi Decoction for the first time. Multiple reaction
      monitoring (MRM) mode was applied for the quantitation at [M-H](-)m/z 253.0->m/z
      225.1 for chrysophanol, [M-H](-) for m/z 283.1->m/z 240.0 physcion and [M-H](
      )m/z 239.0->m/z 211.0 for IS. The analytes were separated on an Agilent Eclipse
      plus C18 column (100mm*2.1mm, 1.8MUm) column within a total running time of
      6.5min using a mixture of 3mM ammonium acetate in water and methanol (95:5, v/v)
      with a time program flow gradient according to the "plus gradient chromatography"
      theory. The inclusion of the ammonium acetate in the UFLC mobile phase
      dramatically improved the detection limit of the tested compounds and decreased
      the interference by matrix effects, which have been referred to as "LC
      electrolyte effects". Finally, we demonstrated the application of a validated
      method in a comparative pharmacokinetic study of rats receiving an oral dose of
      Dahuang Fuzi Decoction or Radix et Rhei Rhizoma, the monarch drug in the
      prescription. Pharmacokinetic parameters showed significant difference between
      the two groups. The achieved comparative pharmacokinetic results were helpful to
      clarify the combination mechanism of Dahuang Fuzi Decoction. 

PMID- 25597889
TI  - Mesoionic Carbene-Gold(I) Catalyzed Bis-Hydrohydrazination of Alkynes with Parent
      Hydrazine.
AB  - A novel synthetic route gives access to mesoionic carbene and cyclopropenylidene
      supported gold chloride complexes. The corresponding cationic MIC-gold complex
      obtained by chloride abstraction allows for the first transition metal-catalyzed
      functionalization of both nitrogens of parent hydrazine. 

PMID- 25597890
TI  - Non-integer viscoelastic constitutive law to model soft biological tissues to in
      vivo indentation.
AB  - PURPOSE: During the last decades, derivatives and integrals of non-integer orders
      are being more commonly used for the description of constitutive behavior of
      various viscoelastic materials including soft biological tissues. Compared to
      integer order constitutive relations, non-integer order viscoelastic material
      models of soft biological tissues are capable of capturing a wider range of
      viscoelastic behavior obtained from experiments. Although integer order models
      may yield comparably accurate results, non-integer order material models have
      less number of parameters to be identified in addition to description of an
      intermediate material that can monotonically and continuously be adjusted in
      between an ideal elastic solid and an ideal viscous fluid. METHODS: In this work,
      starting with some preliminaries on non-integer (fractional) calculus, the
      "spring-pot", (intermediate mechanical element between a solid and a fluid), non
      integer order three element (Zener) solid model, finally a user-defined large
      strain non-integer order viscoelastic constitutive model was constructed to be
      used in finite element simulations. Using the constitutive equation developed, by
      utilizing inverse finite element method and in vivo indentation experiments, soft
      tissue material identification was performed. RESULTS: The results indicate that
      material coefficients obtained from relaxation experiments, when optimized with
      creep experimental data could simulate relaxation, creep and cyclic loading and
      unloading experiments accurately. CONCLUSIONS: Non-integer calculus viscoelastic
      constitutive models, having physical interpretation and modeling experimental
      data accurately is a good alternative to classical phenomenological viscoelastic
      constitutive equations.

PMID- 25597891
TI  - Analysis of triterpenoids and phytosterols in vegetables by thin-layer
      chromatography coupled to tandem mass spectrometry.
AB  - Three TLC methods were used for an initial screening of some common plant
      triterpenoids and phytosterols in cuticular wax extracts of different vegetables
      (zucchini, eggplant, tomato, red pepper, mangold, spinach, lettuce, white-colored
      radicchio di Castelfranco, raddichio Leonardo, white cabbage, red cabbage and
      savoy cabbage). The preliminary experiments showed that the studied vegetables
      are potential sources of triterpenoids and phytosterols. To identify the
      compounds present in the extracts with high certainty, the first TLC-MS(2) method
      was developed for the analysis of eight triterpenoids (lupeol, alpha-amyrin, beta
      amyrin, cycloartenol, cycloartenol acetate, lupeol acetate, lupenone and
      friedelin) and two phytosterols (beta-sitosterol and stigmasterol). This method
      takes the advantages of: (1) a satisfactory separation of the target compounds;
      (2) their differentiation according to the band colors; and (3) the potential of
      their discrimination by the acquired first-order mass (MS) and product ion
      (MS(2)) spectra. Since the closely eluting compounds have complex and similar
      MS(2) spectra, distinguishing between them was possible by the proposed
      characteristic ions. Using a custom-built mass spectral library, the head to tail
      MS(2) spectra comparison of sample test solution zones and standard aided the
      compound identification. In addition to the molecular mass information, the
      developed atmospheric pressure chemical ionization method (APCI) in positive ion
      mode provided structural information, regarding the presence of functional group
      in the molecule. This approach resulted in many positively assigned compounds in
      the investigated vegetable waxes, from which more than a half are reported for
      the first time. 

PMID- 25597892
TI  - Lipidomic profiling of plasma and urine from patients with Gaucher disease during
      enzyme replacement therapy by nanoflow liquid chromatography-tandem mass
      spectrometry.
AB  - Gaucher disease (GD) is a rare genetic disorder that arises from lipid species,
      especially monohexosylceramide (MHC), accumulating in different organs. GD
      results from a beta-glucocerebrosidase deficiency, causing metabolic or
      neurologic complications. This study comprehensively profiled lipids from
      patients and healthy controls to discover active lipid species related to GD.
      Most studies have evaluated lipids from one type of biological sample, such as
      plasma, urine, or spinal fluid, which are the main sources of lipids in human
      bodies. The purpose of this study, however, was to collect and assess both plasma
      and urine samples from a group of individuals, explore the lipids, and select
      characteristic species that show significant differences between controls and
      patients from the two sources. Also, the response of lipids to enzyme replacement
      therapy (ERT), which is targeted to reduce excessive lipid accumulation within
      lysosomes, was investigated by obtaining plasma and urine from patients after
      receiving the therapy. Most lipid species were found in both plasma and urine but
      their concentrations differed, and some species were found in either plasma or
      urine only. Out of 125 plasma and 105 urinary lipids that were identified by nLC
      ESI-MS/MS, 20 plasma and 10 urinary lipids were selected as characteristic
      species for having average concentrations that were significantly increased or
      decreased in patients by greater than 2-fold. Moreover, the concentrations of
      most lipids that showed greater than 2-fold of difference in patients decreased
      after ERT indicating that these species were directly or indirectly affected by
      the therapy. 

PMID- 25597893
TI  - Peak refocusing using subsequent retentive trapping and strong eluent
      remobilization in liquid chromatography: a theoretical optimization study.
AB  - The present paper presents the mathematical expressions for the concentration
      enhancement which can be expected when applying a subsequent retentive trapping
      and strong eluent remobilization process in a packed trap column connected to the
      end of an analytical separation column. The established expressions for the
      optimal loading times, trap dimensions and expected concentration enhancement are
      illustrated and confirmed using numerical simulations of the trapping and release
      process. These simulations also provide a direct insight in how the bands are
      deformed and sharpened during the different steps of the process. The
      simulations, as well as the established expressions, for example show that in the
      backward elution mode the loading time should exceed a minimum value to allow the
      strong eluent front to fully overtake the remobilized band as this is the
      necessary condition to get a completely sharpened peak (in both the backward and
      the forward elution modes). The simulations also show it is very critical that
      this occurs as close as possible to the trap exit, as the bands are most
      sensitive to band broadening once they have been sharpened. The refocusing traps
      should hence be filled with particles producing the smallest possible plate
      heights, and connected to the detector using very short and small i.d. connection
      tubing. It was also found that, if there would be no band broadening in the trap,
      the achievable concentration enhancement would be the same for either a strong or
      weakly retaining trap. The true advantage of a high retention in the trap is that
      it leads to small trap volumes, which in turn minimizes the distance the band has
      to travel to reach the detector. This then minimizes the band broadening
      (inevitable in practice) and helps keeping a high concentration enhancement. 

PMID- 25597894
TI  - Field-flow fractionation of nano- and microparticles in rotating coiled columns.
AB  - Field-flow fractionation (FFF) is a very powerful and versatile set of liquid
      chromatography-like elution methods. However, conventional FFF separations occur
      in thin channels and the sample weight injected is usually less than 1 mg to
      avoid overloading. The fractionation in a rotating coiled column (RCC), which can
      be attributed to sedimentation FFF, enables the handling sample weight to be
      increased at least up to 1 g. An uneven distribution of particles in RCC was
      first observed by Y. Ito et al. in 1966. The work in this direction was continued
      by P.S. Fedotov et al. in 2000. Regularities of the behaviour of nano- and
      microparticles of different size and origin in RCCs with different design
      parameters were systematically studied taking as example silica particles, latex
      beads, quartz sand, clay minerals, and other samples. The basic principles of the
      new FFF method were established. The developed method was applied to the
      speciation analysis of polydisperse environmental samples, in particular, for the
      separation of soils into silt, clay and sand fractions. For the first time, nano-
      and submicron particles of street dust have been separated, weighted,
      characterized by electronic microscopy, and quantitatively analyzed by ICP-MS
      (after digestion). The elements that may be of anthropogenic origin (Zn, Cr, Ni,
      Cu, Cd, Sn, Pb) were found to concentrate mainly in <0.3 and 0.3-1 MUm fractions.
      It has been shown that the concentrations of Cr, Ni, Zn in the finest fraction
      (<0.3 MUm) of street dust can be one order of magnitude higher than the
      concentrations of elements in bulk sample. The fractionation in RCC was also used
      for the recovery of a nearly monodisperse fraction (4.5 MUm) of a chromatographic
      sorbent based on polystyrene-divinylbenzene; impurities remaining from the
      synthesis and smaller particles (1-2 MUm) being removed. Study on the
      fractionation of synthetic samples has demonstrated the applicability of the
      method to the preparative separation and purification of polydisperse materials.

PMID- 25597895
TI  - Ultrahigh performance supercapacitor from lacey reduced graphene oxide
      nanoribbons.
AB  - High performance lacey reduced graphene oxide nanoribbons (LRGONR) were
      chemically synthesized. Holes created during the LRGONR synthesis not only
      enhanced the electrolytic accessibility but destacked all the graphene layers
      through protrusion at edge planes and corrugation in individual graphene. LRGONR
      in a supercapacitor cell showed ultrahigh performance in terms of specific
      capacitance and capacity retention. Consistently in aqueous, nonaqueous, and
      ionic electrolytes, LRGONR symmetric supercapacitor exhibited exceptionally high
      energy/power density, typically 15.06 W h kg(-1)/807 W kg(-1) in aqueous at 1.7 A
      g(-1), 90 W h kg(-1)/2046.8 W kg(-1) in nonaqueous at 1.8 A g(-1), and 181.5 W h
      kg(-1)/2316.8 W kg(-1) in ionic electrolyte at ~1.6 A g(-1). 

PMID- 25597896
TI  - Characterization of fine particulate matter in ambient air by combining TEM and
      multiple spectroscopic techniques--NMR, FTIR and Raman spectroscopy.
AB  - This paper reports a systematic study of the microstructures and spectroscopic
      characteristics of PM2.5 and its potential sources in Beijing by combining
      transmission electron microscopy and multiple spectroscopic techniques: nuclear
      magnetic resonance, Fourier transform infrared and Raman spectroscopy. TEM images
      showed that dominant components of PM2.5 are airborne organic substances with
      many trace metal elements which are associated with combustion sources. NMR
      spectra precisely determined the percentage of carbonaceous speciation in both
      PM2.5 (with spatial and temporal distribution) and its potential sources, and
      distinguished the similarities and differences among them. In FTIR spectra, a
      remarkable peak at 1390 cm(-1) that appeared only in PM2.5 samples was attributed
      to NH4NO3, representing the occurrence of secondary processes. Raman spectra
      revealed certain inorganic compounds including sulfate and nitrate ions. Based on
      the analysis of the decomposition of Raman spectra, spectral parameters provided
      structural information and helped to find potential sources of PM2.5. In the
      space of carbon aromaticity index and ID1/IG, PM2.5 points followed a linear
      distribution which may also be useful in source tracing. The result shows that
      the combined non-destructive methods are efficient to trace the sources of PM2.5.

PMID- 25597897
TI  - Geometric and electronic structures of mono- and di-vacancies in phosphorene.
AB  - The geometric structures, stabilities and diffusions of the monovacancy (MV) and
      divacancy (DV) in two-dimensional phosphorene, as well as their influences on
      their vibrational and electronic properties have been studied by first-principles
      calculations. Two possible MVs and 14 possible DVs have been found in
      phosphorene, in which the MV-(5|9) with a pair of pentagon-nonagon is the ground
      state of MVs, and the DV-(5|8|5) with a pentagon-octagon-pentagon structure is
      the most stable DV. All 14 DVs could be divided into four basic types based upon
      their topological structures and transform between different configurations via
      bond rotations. The diffusion of MV-(5|9) is found to exhibit an anisotropic
      character, preferring to migrate along the zigzag direction in the same half
      layer. The introduction of MV and DV in phosphorene influences its vibrational
      properties, inducing the localized defect modes, which could be used to
      distinguish different vacancy structures. The MVs and DVs also have a significant
      influence on the electronic properties of phosphorene. It is found that the
      phosphorene with MV-(5|9) is a ferromagnetic semiconductor with the magnetic
      moment of 1.0 MUB and a band gap of about 0.211 eV, while the DV induces a direct
      indirect band gap transition. Our calculation results on the MV and DV in
      phosphorene are important for the promising application of the phosphorene in the
      nanoelectronics. 

PMID- 25597898
TI  - Luminescent Pt(II) complexes bearing dual isoquinolinyl pyrazolates: fundamentals
      and applications.
AB  - A series of four Pt(II) metal complexes with trans-arranged isoquinolinyl
      azolates have been prepared, [Pt(Lx)2], x = 1-4, (1-4). The associated chelates
      possess various substituents; namely: one t-butyl (Bu(t)) at the 6-position (L1),
      two Bu(t) groups at the 5,7-positions (L2), one dip (2,6-di-isopropylphenyl)
      group at the 6-position (L3), and a single dip group at the 4-position of the 1
      isoquinolinyl fragment (L4), respectively. Crystal structures of 1 and 4 were
      determined to shed light on the relationship of photophysics and packing
      arrangements. Their photophysical properties were measured and compared, for
      which the solid-state emission spectra of 2 and 4 are nearly identical to the
      solution spectra of all the Pt(II) complexes, showing the formation of isolated
      molecular entities. In contrast, the Pt(II) complexes 1 and 3 are found to be
      sensitive to their morphological states and external stimulus. This is confirmed
      by the gradual red-shifting of the emission with increasing concentration in the
      PMMA matrix, and the eventual formation of the broadened, metal-metal-to-ligand
      charge transfer (MMLCT) emission, by (i) wetting with acetone and drying in air,
      or (ii) grinding with a mortar and pestle, respectively. Organic light-emitting
      diodes (OLEDs) were also fabricated using multiple layered architecture and
      lowered doping concentration (e.g. 8 wt%), the latter is for avoiding dopant
      aggregation in the emitting layer. The associated OLED performances (i.e.
      eta(max) = 11.5%, 8.5%, and 11.2% for 1, 2 and 3) confirmed their suitability and
      potential as dopants for phosphorescent OLEDs.

PMID- 25597899
TI  - From alpha-nucleophiles to functionalized aggregates: exploring the reactivity of
      hydroxamate ion towards esterolytic reactions in micelles.
AB  - Owing to the rising threats of neurotoxic organophosphosphorus compounds, facile
      and efficient decontamination systems are required. Since the last few decades,
      the search for promising alpha-nucleophiles for straightforward and eco-friendly
      decontamination reactions using alpha-nucleophiles has been considerably boosted
      up. Among these, hydroxamic acids have been widely studied due to their potential
      alpha-nucleophilicity towards carbon and phosphorus based esters. This account
      summarizes our research on alpha-nucleophilicity of hydroxamate ions in water and
      micelles towards esterolytic reactions. Efforts of our group in the last few
      years have been collectively judged and compared with the crucial findings of
      researchers in the relevant field. The present article sheds light on the rich
      chemistry of the hydroxamate ion as a perfect candidate to degrade
      organophosphorus esters (i.e. nerve agents, pesticides and their simulants) in
      water, in micelles of conventional surfactants, and in functionalized micelles.
      The current report also provides an insight into the possible nature and
      mechanisms of these reactions. A brief account of the biological activities of
      hydroxamic acids that have recently spurred research in medicine against some
      fatal diseases has been included. 

PMID- 25597900
TI  - A Strategy to enhance Eu3+ emission from LiYF4:Eu nanophosphors and green-to
      orange multicolor tunable, transparent nanophosphor-polymer composites.
AB  - LiYF4:Eu nanophosphors with a single tetragonal phase are synthesized, and
      various strategies to enhance the Eu(3+) emission from the nanophosphors are
      investigated. The optimized Eu(3+) concentration is 35 mol%, and the red emission
      peaks due to the (5)D0 ->(7)FJ (J = 1 and 2) transitions of Eu(3+) ions are
      further enhanced by energy transfer from a sensitizer pair of Ce(3+) and Tb(3+).
      The triple doping of Ce, Tb, and Eu into the LiYF4 host more effectively enhances
      the Eu(3+) emission than the core/shell strategies of
      LiYF4:Eu(35%)/LiYF4:Ce(15%), Tb(15%) and LiYF4:Ce(15%), Tb(15%)/LiYF4:Eu(35%)
      architectures. Efficient energy transfer from Ce(3+) to Eu(3+) through Tb(3+)
      results in three times higher Eu(3+) emission intensity from LiYF4:Ce(15%),
      Tb(15%), Eu(1%) nanophosphors compared with LiYF4:Eu(35%), which contains the
      optimized Eu(3+) concentration. Owing to the energy transfer of Ce(3+) -> Tb(3+)
      and Ce(3+) -> Tb(3+) -> Eu(3+), intense green and red emission peaks are observed
      from LiYF4:Ce(13%), Tb(14%), Eu(1-5%) (LiYF4:Ce, Tb, Eu) nanophosphors, and the
      intensity ratio of green to red emission is controlled by adjusting the Eu(3+)
      concentration. With increasing Eu(3+) concentration, the LiYF4:Ce, Tb, Eu
      nanophosphors exhibit multicolor emission from green to orange. In addition, the
      successful incorporation of LiYF4:Ce, Tb, Eu nanophosphors into
      polydimethylsiloxane (PDMS) facilitates the preparation of highly transparent
      nanophosphor-PDMS composites that present excellent multicolor tunability.

PMID- 25597903
TI  - HLA-B*58:63, a novel allele identified by sequence-based typing in a Chinese bone
      marrow voluntary donor.
AB  - HLA-B*58:63 differs from HLA-B*58:01:01 by one nucleotide at position 248
      resulting in a single amino acid change. 

PMID- 25597901
TI  - A novel urinary long non-coding RNA transcript improves diagnostic accuracy in
      patients undergoing prostate biopsy.
AB  - BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine
      biomarker for the detection of prostate cancer (PCa). Our previous study showed a
      novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched
      benign tissues. The aim of this study was to evaluate the diagnostic value of
      urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA >
      4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE
      first-catch urine specimens prior to prostate biopsies were prospectively
      collected. After the whole transcriptome amplification, quantitative real time
      polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels.
      The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA
      mRNA/FR0348383 mRNA * 1000). The diagnostic value of FR0348383 score was
      evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases
      with urine samples containing sufficient mRNA were included, 94 cases had serum
      PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383
      score was correlated with an increasing probability of a positive biopsy (P <
      0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001),
      PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent
      predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA,
      %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients
      with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a
      probability threshold of 30% in the grey zone cohort, The FR0348383 score would
      save 52.0% of avoidable biopsies without missing any high grade cancers.
      CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for
      detection of PCa with great diagnostic value, especially in the grey zone cohort.
      The application of FR0348383 score in clinical practice might avoid unnecessary
      prostate biopsies and increase the specificity of PCa diagnosis.

PMID- 25597905
TI  - Identification of a novel HLA-DRB1*04 null allele, HLA-DRB1*04:178N.
AB  - A single nucleotide insertion in codon 77 of HLA-DRB*04:05:01 results in a null
      allele, HLA-DRB1*04:178N. 

PMID- 25597904
TI  - HLA-C*07:02:60, a variant of HLA-C*07 found in an unrelated volunteer stem cell
      donor.
AB  - The allele HLA-C*07:02:60 differs from HLA-C*07:02:01:01 by a silent nucleotide
      substitution in exon 4. 

PMID- 25597906
TI  - MOFs-derived copper sulfides embedded within porous carbon octahedra for
      electrochemical capacitor applications.
AB  - A novel, efficient and green MOFs-templated sulfidation route has been developed
      to synthesize Cu(1.96)S-C hybrid composites, in which ultrafine Cu(1.96)S
      nanoparticles are embedded uniformly within porous carbon octahedra. The as
      synthesized composites exhibit high specific capacitance and good cycling
      performance in supercapacitors.

PMID- 25597907
TI  - Mechanical instability at finite temperature.
AB  - Many physical systems including lattices near structural phase transitions,
      glasses, jammed solids and biopolymer gels have coordination numbers placing them
      at the edge of mechanical instability. Their properties are determined by an
      interplay between soft mechanical modes and thermal fluctuations. Here we report
      our investigation of the mechanical instability in a lattice model at finite
      temperature T. The model we used is a square lattice with a phi(4) potential
      between next-nearest-neighbour sites, whose quadratic coefficient kappa can be
      tuned from positive to negative. Using analytical techniques and simulations, we
      obtain a phase diagram characterizing a first-order transition between the square
      and the rhombic phase and different regimes of elasticity, as well as an 'order
      by-disorder' effect that favours the rhombic over other zigzagging
      configurations. We expect our study to provide a framework for the investigation
      of finite-T mechanical and phase behaviour of other systems with a large number
      of floppy modes. 

PMID- 25597908
TI  - AC5 Surgical HemostatTM as an effective hemostatic agent in an anticoagulated rat
      liver punch biopsy model.
AB  - Intra-operative and postoperative bleeding is a major concern in surgical
      procedures for patients taking anticoagulant medications, or where anticoagulants
      are used to prevent potential life-threatening embolic complications. Heparin is
      the anticoagulant used most frequently and has an immediate effect on blood
      clotting, lasting 4 to 6h. Although synthetic self-assembling peptides have been
      shown to achieve rapid hemostasis in small animals, none have adequately
      addressed the potential for hemostasis in the presence of anticoagulant therapy
      in-vivo. Our goal was to investigate the hemostatic activity of a known synthetic
      self-assembling peptide in animals treated and untreated with heparin
      anticoagulation therapy. Using a rat liver puncture model, animals were treated
      with known synthetic peptide AC5 Surgical Hemostatic DeviceTM, or saline
      controls. Time-to-hemostasis and coagulation times were recorded in both
      heparinized and non-heparinized animals. Here we show that AC5TM was able to
      achieve rapid hemostasis equivalently in both heparinized and non-heparinized
      animals. FROM THE CLINICAL EDITOR: Intra-operative and postoperative bleeding is
      a major concern in surgical procedures for patients taking anticoagulant
      medications. In this work the effective hemostasis was demonstrated both in
      heparinized and non-heparinized animals using self-assembling peptides.

PMID- 25597909
TI  - The use of F-response in defining interstimulus intervals appropriate for LTP
      like plasticity induction in lower limb spinal paired associative stimulation.
AB  - BACKGROUND: In spinal paired associative stimulation (PAS), orthodromic volleys
      are induced by transcranial magnetic stimulation (TMS) in upper motor neurons,
      and antidromic volleys by peripheral nerve stimulation (PNS) in lower motor
      neurons of human corticospinal tract. The volleys arriving synchronously to the
      corticomotoneuronal synapses induce spike time-dependent plasticity in the spinal
      cord. For clinical use of spinal PAS, it is important to develop protocols that
      reliably induce facilitation of corticospinal transmission. Due to variability in
      conductivity of neuronal tracts in neurological patients, it is beneficial to
      estimate interstimulus interval (ISI) between TMS and PNS on individual basis.
      Spinal root magnetic stimulation has previously been used for this purpose in
      spinal PAS targeting upper limbs. However, at lumbar level this method does not
      take into account the conduction time of spinal nerves of the cauda equina in the
      spinal canal. NEW METHOD: For lower limbs spinal PAS, we propose estimating
      appropriate ISIs on the basis of F-response and motor-evoked potential (MEP)
      latencies. The use of navigation in TMS and ensuring correct PNS electrode
      placement with F-response recording enhances the precision of the method.
      RESULTS: Our protocol induced 186+/-17% (mean+/-STE) MEP amplitude facilitation
      in healthy subjects, being effective in all subjects and nerves tested.
      COMPARISON WITH EXISTING METHOD: We report for the first time the individual
      estimation of ISIs in spinal PAS for lower limbs. CONCLUSIONS: Estimation of ISI
      on the basis of F and MEP latencies is sufficient to effectively enhance
      corticospinal transmission by lower limb spinal PAS in healthy subjects.

PMID- 25597911
TI  - Models of ADHD: Five ways smaller sooner is better.
AB  - BACKGROUND: In the delay discounting paradigm choices are made between a good of
      small utility available soon (SS) vs. a good of greater utility available later
      (LL). Versions of the task may be used with human and non-human subjects, they
      generate characteristic data, and are of relevance the topic of this special
      issue, the imputed impulsivity of organisms categorized as ADHD, and animal
      models of ADHD. METHOD: Mathematical models of judgment were formulated. The
      first model adds the utility of a good to the utility of the delay. It provides
      distinct information about future perspective, the marginal utility of the goods
      offered, and the relative weight on delay. It grounds hyperbolic discounting. It
      predicts slower rates of discount for more preferred goods. It can reduce to an
      exponential function on future perspective time. When choice is mediated by
      conditioning, not judgment, a model of conditioned reinforcement strength is
      written. For studies where only the degree of preference for the LL is reported,
      a Thurstonian model of discrimination provides a shell that embraces all of the
      earlier models, providing additional information about the precision and bias of
      those preferential judgments. COMPARISON WITH OTHER MODELS: All other prominent
      models are nested within, or approximations to, the models described here.
      RESULTS: The models are fit to exemplary data. They provide some support for
      theories of delay aversion, and explanations for some inconsistencies in the
      literature. They involve parameters of general utility and provide connection to
      economic models.

PMID- 25597912
TI  - Room-temperature exciton coherence and dephasing in two-dimensional
      nanostructures.
AB  - Electronic coherence has attracted considerable attention for its possible role
      in dynamical processes in molecular systems. However, its detection is challenged
      by inhomogeneous line broadening and interference with vibrational coherences. In
      particular, reports of 'persistent' coherent exciton superpositions at room
      temperature remain controversial, as the related transitions give typically
      shorter optical dephasing times of about 10-20 fs. To rationalize these reported
      long-lived coherences, several models have been proposed, involving strong
      correlation in the mechanisms of decoherence or that electronic coherences may be
      sustained by resonant vibrational modes. Here we report a decisive example of
      electronic coherence occurring in a chemical system in a 'warm and wet' (room
      temperature solution) environment, colloidal semiconductor nanoplatelets, where
      details are not obscured by vibrational coherences nor ensemble dephasing.
      Comparing the exciton and optical coherence times evidences a partial correlation
      of fluctuations underlying dephasing and allows us to elucidate decoherence
      mechanisms occurring in these samples. 

PMID- 25597910
TI  - Low-cost blast wave generator for studies of hearing loss and brain injury: blast
      wave effects in closed spaces.
AB  - BACKGROUND: Military personnel and civilians living in areas of armed conflict
      have increased risk of exposure to blast overpressures that can cause significant
      hearing loss and/or brain injury. The equipment used to simulate comparable blast
      overpressures in animal models within laboratory settings is typically very large
      and prohibitively expensive. NEW METHOD: To overcome the fiscal and space
      limitations introduced by previously reported blast wave generators, we developed
      a compact, low-cost blast wave generator to investigate the effects of blast
      exposures on the auditory system and brain. RESULTS: The blast wave generator was
      constructed largely from off the shelf components, and reliably produced blasts
      with peak sound pressures of up to 198dB SPL (159.3kPa) that were qualitatively
      similar to those produced from muzzle blasts or explosions. Exposure of adult
      rats to 3 blasts of 188dB peak SPL (50.4kPa) resulted in significant loss of
      cochlear hair cells, reduced outer hair cell function and a decrease in
      neurogenesis in the hippocampus. COMPARISON TO EXISTING METHODS: Existing blast
      wave generators are typically large, expensive, and are not commercially
      available. The blast wave generator reported here provides a low-cost method of
      generating blast waves in a typical laboratory setting. CONCLUSIONS: This compact
      blast wave generator provides scientists with a low cost device for investigating
      the biological mechanisms involved in blast wave injury to the rodent cochlea and
      brain that may model many of the damaging effects sustained by military personnel
      and civilians exposed to intense blasts.

PMID- 25597913
TI  - Supermicrosurgical deep lymphatic vessel-to-venous anastomosis for a breast
      cancer-related arm lymphedema with severe sclerosis of superficial lymphatic
      vessels.
AB  - Lymphatic supermicrosurgery or supermicrosurgical lymphaticovenular anastomosis
      (LVA) is becoming popular for the treatment of compression-refractory upper
      extremity lymphedema (UEL) with its effectiveness and minimally invasiveness. In
      conventional LVA, superficial lymphatic vessels are used for anastomosis, but its
      treatment efficacy would be minimum when superficial lymphatic vessels are
      severely sclerotic. Theoretically, deep lymphatic vessels can be used for LVA,
      but no clinical case has been reported regarding deep lymphatic vessel-to-venous
      anastomosis (D-LVA). We report a breast cancer-related UEL case treated with D
      LVA, in which a less-sclerotic deep lymphatic vessel was useful for anastomosis
      but superficial lymphatic vessels were not due to severe sclerosis. A 62-year-old
      female suffered from an 18-year history of compression-refractory right UEL after
      right breast cancer treatments, and underwent LVA under local infiltration
      anesthesia. Because superficial lymphatic vessels found in surgical fields were
      all severely sclerotic, a deep lymphatic vessel was dissected at the cubital
      fossa. A 0.50-mm deep lymphatic vessel running along the brachial artery was
      supermicrosurgically anastomosed to a nearby 0.40-mm vein. At postoperative 12
      months, her right UEL index decreased from 134 to 118, and she could reduce
      compression frequency from every day to 1-2 days per week to maintain the reduced
      lymphedematous volume. D-LVA may be a useful option for the treatment of
      compression-refractory UEL, when superficial lymphatic vessels are severely
      sclerotic. (c) 2015 Wiley Periodicals, Inc. Microsurgery 37:156-159, 2017.

PMID- 25597914
TI  - Reference system of competence and engagement in adapted physical activities of
      people with recent spinal cord injury.
AB  - PURPOSE: This study tested whether persons with Recent Spinal Cord Injury (RSCI)
      who practice adapted physical activities (APA) and those who do not differ with
      regard to achievement goals, physical self-perceptions, and global self-esteem.
      METHOD: Adults with RSCI in rehabilitation centers voluntarily completed
      questionnaires of achievement goals and self-esteem. Then, based on whether they
      engaged or not in APA programs, they were considered participants or non
      participants in APA. RESULTS: Compared to participants in APA, non-participants
      were more oriented toward mastery-avoidance goals and had lower scores of
      physical self-worth and global self-esteem. No differences were found for other
      achievement goals and for low-level dimensions of physical self. CONCLUSIONS:
      These findings suggest that mastery-avoidance goals are associated with a
      maladaptive motivational pattern when intrapersonal comparison conveys a threat
      for the self. Practical implications for rehabilitation programs for persons with
      RSCI are offered. IMPLICATIONS FOR REHABILITATION: Adapted Physical Activities
      (APA) programs are supervised physical activity programs in which the choice of
      the activity as well as the frequency, the duration, and the intensity of
      practice are adapted to the inpatients' capabilities. Attempts to master physical
      activities can be seen as threatening experiences to be avoided by persons with
      Recent Spinal Cord Injury (RSCI) in rehabilitation centers. Comparing one's
      capabilities in physical activities with those of other persons with RSCI is not
      motivationally detrimental with respect to the practice of these activities. Upon
      persons with RSCI' arrival in rehabilitation centers, physical educators should
      promote a friendly competitive climate in the practice of APA to help inpatients
      recover healthy levels of physical self-perceptions and global self-esteem as
      well as motivation to exercise.

PMID- 25597915
TI  - Self-efficacy as a longitudinal predictor of perceived cognitive impairment in
      individuals with multiple sclerosis.
AB  - OBJECTIVES: To determine whether self-efficacy longitudinally predicts 2 types of
      perceived cognitive impairment (PCI) in multiple sclerosis (MS): general
      cognitive functioning and executive functioning; and secondarily to assess
      whether self-efficacy mediates the relationships between depression, fatigue, and
      PCI. DESIGN: Longitudinal analysis of self-report survey data collected over 3
      years. Hierarchical regression analyses examined the relationship between self
      efficacy and PCI, adjusting for depression and fatigue. Additional analyses
      tested self-efficacy as a mediator between depression, fatigue, and PCI. SETTING:
      Community. PARTICIPANTS: Community-dwelling individuals with MS (N=233; age
      range, 22-83y) were recruited from a larger longitudinal survey study of
      individuals with MS (N=562). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Primary outcome measures were the Applied Cognition-General Concerns
      and the Applied Cognition-Executive Function domains of the Quality of Life in
      Neurological Disorders (NeuroQoL) measures. RESULTS: Self-efficacy was
      significantly correlated with PCI at baseline (r=.40-.53) and 3 years later
      (r=.36-.44). In multivariate regression analyses, self-efficacy was a significant
      longitudinal predictor of PCI, both for general cognitive functioning (beta=.20,
      P<.01) and executive functioning (beta=.16, P<.05). Self-efficacy partially
      mediated the relationships between depression, fatigue, and PCI. CONCLUSIONS:
      Self-efficacy may influence how individuals with MS perceive their cognitive
      functioning over time. Interventions that target self-efficacy, particularly
      early in the disease course, may lead to improvements in PCI, as well as
      improvements in fatigue and depression.

PMID- 25597916
TI  - Postnatal penile growth concurrent with mini-puberty predicts later sex-typed
      play behavior: Evidence for neurobehavioral effects of the postnatal androgen
      surge in typically developing boys.
AB  - The masculinizing effects of prenatal androgens on human neurobehavioral
      development are well established. Also, the early postnatal surge of androgens in
      male infants, or mini-puberty, has been well documented and is known to influence
      physiological development, including penile growth. However, neurobehavioral
      effects of androgen exposure during mini-puberty are largely unknown. The main
      aim of the current study was to evaluate possible neurobehavioral consequences of
      mini-puberty by relating penile growth in the early postnatal period to
      subsequent behavior. Using multiple linear regression, we demonstrated that
      penile growth between birth and three months postnatal, concurrent with mini
      puberty, significantly predicted increased masculine/decreased feminine behavior
      assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3
      to 4years of age. When we controlled for other potential influences on
      masculine/feminine behavior and/or penile growth, including variance in androgen
      exposure prenatally and body growth postnally, the predictive value of penile
      growth in the early postnatal period persisted. More specifically, prenatal
      androgen exposure, reflected in the measurement of anogenital distance (AGD), and
      early postnatal androgen exposure, reflected in penile growth from birth to
      3months, were significant predictors of increased masculine/decreased feminine
      behavior, with each accounting for unique variance. Our findings suggest that
      independent associations of PSAI with AGD at birth and with penile growth during
      mini-puberty reflect prenatal and early postnatal androgen exposures
      respectively. Thus, we provide a novel and readily available approach for
      assessing effects of early androgen exposures, as well as novel evidence that
      early postnatal aes human neurobehavioral development. 

PMID- 25597917
TI  - The emission of stress-induced 22-kHz calls in female rats is independent of
      testosterone levels.
AB  - Although emission of ultrasonic calls in rats induced by stress, referred to as
      "22-kHz calls," is dependent on circulating testosterone levels in males, it is
      still unknown whether the same testosterone-based regulation is applicable to
      female rats. In this study, we investigated the sex difference in the emission of
      air-puff-induced 22-kHz calls in rats on the basis of the hypothesis that female
      rats would emit fewer 22-kHz calls, and assessed whether male-like circulating
      testosterone levels can also influence the emission of 22-kHz calls in females.
      The experimental results showed that female rats emit significantly fewer 22-kHz
      calls than male rats. However, male-like circulating testosterone levels have
      little effect on the emission of 22-kHz calls in females. Hence, it is suggested
      that there is a sex difference in stress-induced 22-kHz calls in rats and, in
      contrast to male rats, the emission of 22-kHz calls in female rats may be
      independent of circulating testosterone levels, as tested in response to air-puff
      stimulation. 

PMID- 25597919
TI  - Physicochemical properties and storage stability of lutein microcapsules prepared
      with maltodextrins and sucrose by spray drying.
AB  - The purpose of this study was to determine the physicochemical properties of
      lutein microcapsules. Nine types of lutein microcapsules were prepared in order
      to determine their encapsulation efficiency and yield. Results show that lutein
      microcapsules with maltodextrin M040 and sucrose at the weight ratio of 3:1
      (designated as M040:1) had the highest encapsulation efficiency (90.1%) among the
      lutein microcapsules, as well as a higher encapsulation yield (90.4%). The onset
      glass transition temperatures (Tgi ) and the surface dents of the lutein
      microcapsules decreased as the dextrose equivalent value of maltodextrin and the
      weight ratio of sucrose increased. Enthalpy relaxation experiments were conducted
      for the lutein microcapsules M040:1 at (Tgi - 5) , (Tgi - 10), and (Tgi - 15) 
      degrees C, and the obtained data were fitted to the Kohlrausch-Williams-Watts
      model. Results show that the mean relaxation time (tau) (316 h) of M040:1 lutein
      microcapsules aged at (Tgi - 15)  degrees C was greater than the tau (161 h) at
      (Tgi - 10)  degrees C and tau (60.5 h) at (Tgi - 5)  degrees C. Effects of
      temperature and oxygen transmission rates for package film on the storage
      stability of M040:1 lutein microcapsules were also investigated. Findings show
      that rates of lutein degradation and color change increased by an order of
      magnitude as storage temperature (4 to 97  degrees C) and oxygen transmission
      rate of the package film (0.018 to 62.8 cc/m(2) day) increased. These results
      suggest that lutein is highly unstable and susceptible to thermal and oxidative
      degradations. However, microencapsulation with appropriate wall materials of
      higher relaxation time and high oxygen barrier packaging can increase the storage
      life. 

PMID- 25597918
TI  - The orally active urotensin receptor antagonist, KR36676, attenuates cellular and
      cardiac hypertrophy.
AB  - BACKGROUND AND PURPOSE: Blockade of the actions of urotensin-II (U-II) mediated
      by the urotensin (UT) receptor should improve cardiac function and prevent
      cardiac remodelling in cardiovascular disease. Here, we have evaluated the
      pharmacological properties of the recently identified UT receptor antagonist, 2
      (6,7-dichloro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-methyl-N-(2-(pyrrolidin-1
      yl)-1-(4-(thiophen-3-yl)phenyl) ethyl)acetamide (KR36676). EXPERIMENTAL APPROACH:
      Pharmacological properties of KR36676 were studied in a range of in vitro assays
      (receptor binding, calcium mobilization, stress fibre formation, cellular
      hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by
      transverse aortic constriction (TAC) or myocardial infarction (MI). KEY RESULTS:
      KR36676 displayed high binding affinity for the UT receptor (Ki : 0.7 nM),
      similar to that of U-II (0.4 nM), and was a potent antagonist at that receptor
      (IC50 : 4.0 nM). U-II-induced stress fibre formation and cellular hypertrophy
      were significantly inhibited with low concentrations of KR36676 (>=0.01 MUM).
      Oral administration of KR36676 (30 mg.kg(-1) ) in a TAC model in mice attenuated
      cardiac hypertrophy and myocardial fibrosis. Moreover, KR36676 restored cardiac
      function and myocyte size in rats with MI-induced cardiac hypertrophy.
      CONCLUSIONS AND IMPLICATIONS: A highly potent UT receptor antagonist exerted anti
      hypertrophic effects not only in infarcted rat hearts but also in pressure
      overloaded mouse hearts. KR36676 could be a valuable pharmacological tool in
      elucidating the complicated physiological role of U-II and UT receptors in
      cardiac hypertrophy.

PMID- 25597920
TI  - Cell wall traits as potential resources to improve resistance of durum wheat
      against Fusarium graminearum.
AB  - BACKGROUND: Fusarium graminearum, one of the causal agents of Fusarium Head
      Blight (FHB, scab), leads to severe losses in grain yield and quality due to the
      production of mycotoxins which are harmful to human and livestock. Different
      traits for FHB resistance in wheat were identified for common wheat (Triticum
      aestivum L.) while the sources of FHB resistance in durum wheat (Triticum
      turgidum ssp. Durum), one of the cereals most susceptible to F. graminearum
      infection, have not been found. New lines of evidence indicate that content and
      composition of cell wall polymers affect the susceptibility of the wall to
      degrading enzymes produced by pathogens during infection and can play a role in
      the outcome of host-pathogen interactions. The objective of our research is to
      identify potential cell wall biochemical traits linked to Fusariosis resistance
      to be transferred from a resistant common wheat to a susceptible durum wheat
      line. RESULTS: A detailed analysis of cell wall composition in spikes isolated
      from a highly resistant common wheat accession "02-5B-318", a breeding line
      derived from the FHB-resistant Chinese cv. Sumai-3 and a high susceptible durum
      wheat cv. Saragolla was performed. Significant differences in lignin monolignols
      composition, arabinoxylan (AX) substitutions and pectin methylesterification were
      found between resistant and susceptible plants. We isolated and characterized a
      pectin methylesterase gene WheatPME1, which we found being down regulated in the
      FHB-resistant line and induced by fungal infection in the susceptible wheat.
      CONCLUSIONS: Our results indicate cell wall traits differing between the FHB
      sensitive and resistant wheat genotypes, possibly related to FHB-resistance, and
      identify the line 02-5B-318R as a potential resource of such traits. Evidence
      suggests that WheatPME1 is involved in wheat response to F. graminearum.

PMID- 25597921
TI  - Antibodies against the majority subunit of type IV Pili disperse nontypeable
      Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic
      resolution of experimental otitis media.
AB  - Despite resulting in a similar overall outcome, unlike antibodies directed
      against the DNABII protein, integration host factor (IHF), which induce
      catastrophic structural collapse of biofilms formed by nontypeable Haemophilus
      influenzae (NTHI), those directed against a recombinant soluble form of PilA [the
      majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual 'top
      down' dispersal of NTHI from biofilms. This dispersal occurred via a mechanism
      that was dependent upon expression of both PilA (and by inference, Tfp) and
      production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to
      a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the
      powerful adjuvant dmLT and delivered via a noninvasive transcutaneous
      immunization route induced an immune response that targeted two important
      determinants essential for biofilm formation by NTHI. This resulted in
      significantly earlier eradication of NTHI from both planktonic and adherent
      populations in the middle ear, disruption of mucosal biofilms already resident
      within middle ears prior to immunization and rapid resolution of signs of disease
      in an animal model of experimental otitis media. These data support continued
      development of this novel combinatorial immunization approach for resolution
      and/or prevention of multiple diseases of the respiratory tract caused by NTHI. 

PMID- 25597922
TI  - Zinc-bearing zeolite clinoptilolite improves tissue zinc accumulation in laying
      hens by enhancing zinc transporter gene mRNA abundance.
AB  - A study was conducted to investigate effects of zinc-bearing zeolite
      clinoptilolite (ZnCP), as an alternative for zinc sulfate (ZnSO4), on laying
      performance, tissue Zn accumulation and Zn transporter genes expression in laying
      hens. Hy-Line Brown laying hens were allocated to three treatments, each of which
      had six replicates with 15 hens per replicate, receiving basal diet supplemented
      with ZnSO4 (control, 80 mg Zn/kg diet), 0.23% ZnCP (40.25 mg Zn/kg diet) and
      0.46% ZnCP (80.50 mg Zn/kg diet) for 8 weeks, respectively. Compared with
      control, hens fed diet containing 0.23% ZnCP had similar Zn content in measured
      tissues (P > 0.05). A higher ZnCP inclusion (0.46%) enhanced Zn accumulation in
      liver (P < 0.05) and pancreas (P < 0.05). In addition, ZnCP inclusion increased
      blood iron (Fe) content (P < 0.05). ZnCP supplementation enhanced jejunal
      metallothionein-4 (MT-4) messenger RNA (mRNA) abundance (P < 0.05). ZnCP
      inclusion at a higher level (0.46%) increased mRNA expression of MT-4 in pancreas
      (P < 0.05) and zinc transporter-1 (ZnT-1) in jejunum (P < 0.05). The highest ZnT
      2 mRNA abundance in jejunum was found in hens fed 0.23% ZnCP inclusion diet (P <
      0.05). The results indicated that ZnCP reached a higher bioavailability as
      compared with ZnSO4 as evidenced by enhanced tissue Zn accumulation and Zn
      transporter genes expression.

PMID- 25597923
TI  - Toward the development of effective transmission-blocking vaccines for malaria.
AB  - The continued global burden of malaria can in part be attributed to a complex
      lifecycle, with both human hosts and mosquito vectors serving as transmission
      reservoirs. In preclinical models of vaccine-induced immunity, antibodies to
      parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit
      parasite survival in the insect midgut as judged by ex vivo functional studies
      such as the membrane feeding assay. In an era of renewed political momentum for
      malaria elimination and eradication campaigns, such observations have fueled
      support for the development and implementation of so-called transmission-blocking
      vaccines. While leading candidates are being evaluated using a variety of
      promising vaccine platforms, the field is also beginning to capitalize on global
      '-omics' data for the rational genome-based selection and unbiased
      characterization of parasite and mosquito proteins to expand the candidate list.
      This review covers the progress and prospects of these recent developments. 

PMID- 25597924
TI  - Complementary therapies for acne vulgaris.
AB  - BACKGROUND: Acne is a chronic skin disease characterised by inflamed spots and
      blackheads on the face, neck, back, and chest. Cysts and scarring can also occur,
      especially in more severe disease. People with acne often turn to complementary
      and alternative medicine (CAM), such as herbal medicine, acupuncture, and dietary
      modifications, because of their concerns about the adverse effects of
      conventional medicines. However, evidence for CAM therapies has not been
      systematically assessed. OBJECTIVES: To assess the effects and safety of any
      complementary therapies in people with acne vulgaris. SEARCH METHODS: We searched
      the following databases from inception up to 22 January 2014: the Cochrane Skin
      Group Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL; 2014,Issue 1), MEDLINE (from 1946), Embase (from 1974), PsycINFO (from
      1806), AMED (from 1985), CINAHL (from 1981), Scopus (from 1966), and a number of
      other databases listed in the Methods section of the review. The Cochrane CAM
      Field Specialised Register was searched up to May 2014. We also searched five
      trials registers and checked the reference lists of articles for further
      references to relevant trials. SELECTION CRITERIA: We included parallel-group
      randomised controlled trials (or the first phase data of randomised cross-over
      trials) of any kind of CAM, compared with no treatment, placebo, or other active
      therapies, in people with a diagnosis of acne vulgaris. DATA COLLECTION AND
      ANALYSIS: Three authors collected data from each included trial and evaluated the
      methodological quality independently. They resolved disagreements by discussion
      and, as needed, arbitration by another author. MAIN RESULTS: We included 35
      studies, with a total of 3227 participants. We evaluated the majority as having
      unclear risk of selection, attrition, reporting, detection, and other biases.
      Because of the clinical heterogeneity between trials and the incomplete data
      reporting, we could only include four trials in two meta-analyses, with two
      trials in each meta-analysis. The categories of CAM included herbal medicine,
      acupuncture, cupping therapy, diet, purified bee venom (PBV), and tea tree oil. A
      pharmaceutical company funded one trial; the other trials did not report their
      funding sources.Our main primary outcome was 'Improvement of clinical signs
      assessed through skin lesion counts', which we have reported as 'Change in
      inflammatory and non-inflammatory lesion counts', 'Change of total skin lesion
      counts', 'Skin lesion scores', and 'Change of acne severity score'. For 'Change
      in inflammatory and non-inflammatory lesion counts', we combined 2 studies that
      compared a low- with a high-glycaemic-load diet (LGLD, HGLD) at 12 weeks and
      found no clear evidence of a difference between the groups in change in non
      inflammatory lesion counts (mean difference (MD) -3.89, 95% confidence interval
      (CI) -10.07 to 2.29, P = 0.10, 75 participants, 2 trials, low quality of
      evidence). However, although data from 1 of these 2 trials showed benefit of LGLD
      for reducing inflammatory lesions (MD -7.60, 95% CI -13.52 to -1.68, 43
      participants, 1 trial) and total skin lesion counts (MD -8.10, 95% CI -14.89 to 
      1.31, 43 participants, 1 trial) for people with acne vulgaris, data regarding
      inflammatory and total lesion counts from the other study were incomplete and
      unusable in synthesis.Data from a single trial showed potential benefit of tea
      tree oil compared with placebo in improving total skin lesion counts (MD -7.53,
      95% CI -10.40 to -4.66, 60 participants, 1 trial, low quality of evidence) and
      acne severity scores (MD -5.75, 95% CI -9.51 to -1.99, 60 participants, 1 trial).
      Another trial showed pollen bee venom to be better than control in reducing
      numbers of skin lesions (MD -1.17, 95% CI -2.06 to -0.28, 12 participants, 1
      trial).Results from the other 31 trials showed inconsistent effects in terms of
      whether acupuncture, herbal medicine, or wet-cupping therapy were superior to
      controls in increasing remission or reducing skin lesions.Twenty-six of the 35
      included studies reported adverse effects; they did not report any severe adverse
      events, but specific included trials reported mild adverse effects from herbal
      medicines, wet-cupping therapy, and tea tree oil gel.Thirty trials measured two
      of our secondary outcomes, which we combined and expressed as 'Number of
      participants with remission'. We were able to combine 2 studies (low quality of
      evidence), which compared Ziyin Qinggan Xiaocuo Granule and the antibiotic,
      minocycline (100 mg daily) (worst case = risk ratio (RR) 0.49, 95% CI 0.09 to
      2.53, 2 trials, 206 participants at 4 weeks; best case = RR 2.82, 95% CI 0.82 to
      9.06, 2 trials, 206 participants at 4 weeks), but there was no clear evidence of
      a difference between the groups.None of the included studies assessed
      'Psychosocial function'.Two studies assessed 'Quality of life', and significant
      differences in favour of the complementary therapy were found in both of them on
      'feelings of self-worth' (MD 1.51, 95% CI 0.88 to 2.14, P < 0.00001, 1 trial, 70
      participants; MD 1.26, 95% CI 0.20 to 2.32, 1 trial, 46 participants) and
      emotional functionality (MD 2.20, 95% CI 1.75 to 2.65, P < 0.00001, 1 trial, 70
      participants; MD 0.93, 95% CI 0.17 to 1.69, 1 trial, 46 participants).Because of
      limitations and concerns about the quality of the included studies, we could not
      draw a robust conclusion for consistency, size, and direction of outcome effects
      in this review. AUTHORS' CONCLUSIONS: There is some low-quality evidence from
      single trials that LGLD, tea tree oil, and bee venom may reduce total skin
      lesions in acne vulgaris, but there is a lack of evidence from the current review
      to support the use of other CAMs, such as herbal medicine, acupuncture, or wet
      cupping therapy, for the treatment of this condition. There is a potential for
      adverse effects from herbal medicines; however, future studies need to assess the
      safety of all of these CAM therapies. Methodological and reporting quality
      limitations in the included studies weakened any evidence. Future studies should
      be designed to ensure low risk of bias and meet current reporting standards for
      clinical trials.

PMID- 25597925
TI  - Tailoring psychotherapy in patients with personality disorders: Matching the
      level of psychological strengths to the level of stabilizing versus destabilizing
      psychotherapy.
AB  - BACKGROUND: Clinical evidence suggests that patients high on psychological
      strengths profit more from destabilizing psychotherapy, whereas patients low on
      strengths profit more from stabilizing psychotherapy. This matching hypothesis
      was tested. METHODS: This quasi-experimental study was conducted between 2003 and
      2008 in 735 patients with personality disorders from 6 psychotherapy centers in
      the Netherlands. Patients were assigned to different levels of stabilizing and
      destabilizing psychotherapies. Levels of psychological strengths were measured.
      We used multilevel modeling to estimate outcome at 12 months after baseline. The
      propensity score controlled for initial differences at baseline. RESULTS: The
      findings show that destabilizing psychotherapies have slightly better outcomes
      than stabilizing psychotherapies. Patients high on psychological strengths
      improve slightly more than patients low on psychological strengths. The observed
      interaction effect contradicted our hypothesis. CONCLUSION: The results imply
      that destabilizing psychotherapies can be considered as first treatment option
      for patients both high and low on psychological strengths.

PMID- 25597926
TI  - AWAJI criteria are not always superior to the previous criteria: A meta-analysis.
AB  - INTRODUCTION: Recently, some authors have claimed that the Awaji criteria (AC)
      are not always more sensitive than the revised El Escorial criteria (rEEC) in
      amyotrophic lateral sclerosis (ALS). METHODS: A meta-analysis examined 2
      prospective and 7 retrospective studies, which included 1,121 ALS patients, to
      compare AC and rEEC for early diagnosis of ALS. RESULTS: AC led to an 11% greater
      likelihood of being classified into the categories "clinically definite" or
      "clinically probable", while if confined to the "clinically probable - laboratory
      supported (LS)" category, this effect was 40% higher with the rEEC (95% cnfidence
      interval, 3-82%; I2=98%). Specifically, AC downgraded 20% of the rEEC "clinically
      probable - LS" category to the AC "clinically possible". CONCLUSIONS: Despite
      overall superiority of AC, this meta-analysis shows that it is not always more
      sensitive than rEEC. These results are related to the requirement for 2 upper
      motor neuron signs in the AC "clinically probable" category.

PMID- 25597927
TI  - Non-centrosymmetric homochiral supramolecular polymers of tetrahedral
      subphthalocyanine molecules.
AB  - A combination of spectroscopy (UV/Vis absorption, emission, and circular
      dichroism), microscopy (AFM and TEM), and computational studies reveal the
      formation of non-centrosymmetric homochiral columnar subphthalocyanine
      assemblies. These assemblies form through a cooperative supramolecular
      polymerization process driven by hydrogen-bonding between amide groups, pi-pi
      stacking, and dipolar interactions between axial B-F bonds.

PMID- 25597928
TI  - The Impact on the Family of Four Neurogenetic Syndromes: A Comparative Study of
      Parental Views.
AB  - Research on behavioral phenotypes in neurogenetic syndromes has primarily focused
      on aspects of the affected child's behavior. However, the impact of having a
      child with a neurogenetic syndrome on aspects of family functioning can be
      significant and differ across syndromes. Parents (N = 381) of school-aged
      children with one of four neurogenetic syndromes: fragile X Syndrome (FXS),
      Prader Willi Syndrome (PWS), Williams Syndrome (WS) and 22q11.2 (22qDEL) were
      asked about challenges, restrictions, future concerns and positive aspects
      arising from having an affected child. Factors associated with these aspects were
      analysed via logistic regression. Restrictions were most often reported by
      parents of children with FXS. The factors significantly (p < .01) associated with
      the parent reported restrictions were the presence of a behavioral/psychiatric
      condition and a lower level of receptive communication. The challenges endorsed
      most often were the child's learning and social skills difficulties. Significant
      differences (p < .01) between the syndromes were noted for many of the
      challenges. Ninety-six percent of parents endorsed at least one positive aspect
      but most aspects endorsed did not differ between the genetic syndromes. Having a
      behavioral/psychiatric condition was the only factor significantly associated (p
      < .01) with endorsing a lower number of positive aspects and a higher number of
      challenges. There are some commonalities but also significant differences across
      syndromes regarding views on how a child's syndrome affects family functioning.
      These differences may be important with regard to how to counsel and support
      affected families. The presence of behavioral/psychiatric conditions is an
      important predictor of negative family outcome across the syndromes.

PMID- 25597929
TI  - Incidence and prevalence of diabetes in children aged <15 yr in Fiji, 2001-2012.
AB  - OBJECTIVE: Determine the incidence and prevalence of diabetes in children <15 yr
      in Fiji. METHODS: Data on all new cases from 2001 to 2012 was collected from the
      three paediatric diabetes services through the International Diabetes Federation
      Life for a Child Program. There was no formal secondary ascertainment source,
      however the medical community is small and all known cases are believed to be
      included. RESULTS: Forty-two children aged <15 yr were diagnosed from 2001 to
      2012. Twenty-eight were type 1 (66.7%), 13 type 2 (31.0%), and 1 (2.4%) had
      neonatal diabetes (INS gene mutation). For type 1, the mean +/- standard
      deviation (SD) age of diagnosis was 10.2 +/- 2.9 yr, with similar proportions of
      males and females. Four (14.3%) were native Fijians and 24 (86.7%) were of Indo
      Fijian descent (p < 0.001). The mean annual incidence of type 1 in children <15
      yr was 0.93/100,000 and prevalence in 2012 was 5.9/100,000. There was no evidence
      of a rise in incidence, but low numbers would preclude recognition of a small
      increased rate. For the 13 cases of type 2 diabetes, the mean SD age of diagnosis
      was 12.2 +/- 2.7 yr, 85% were female (p < 0.01), and 85% were of Indo-Fijian
      descent (p = 0.001). The mean annual incidence of type 2 was 0.43/100,000 and
      2012 prevalence was 2.4/100,000. No child with diabetes aged <15 yr died during
      the 12-yr period. CONCLUSIONS: The incidence of type 1 diabetes in Fiji is very
      low. Furthermore, its occurrence is markedly more frequent in Indo-Fijians than
      in native Fijians. Type 2 and neonatal diabetes also occur.

PMID- 25597931
TI  - An updated estimate of the body dimensions of US children.
AB  - Anthropometric data from children are important for product design and the
      promulgation of safety standards. The last major detailed study of child
      anthropometry in the USA was conducted more than 30 years ago. Subsequent
      demographic changes and the increased prevalence of overweight and obesity render
      those data increasingly obsolete. A new, large-scale anthropometric survey is
      needed. As an interim step, a new anthropometric synthesis technique was used to
      create a virtual population of modern children, each described by 84
      anthropometric measures. A subset of these data was validated against limited
      modern data. Comparisons with data from the 1970s showed significant changes in
      measures of width and circumference of the torso, arms and legs. Measures of
      length and measurements of the head, face, hands and feet exhibited little
      change. The new virtual population provides guidance for a comprehensive child
      anthropometry survey and could improve safety and accommodation in product
      design. Practitioner Summary: This research reviews the inadequacies of available
      sources of US child anthropometry as a result of the rise in the rates of
      overweight and obesity. A new synthesised database of detailed modern child
      anthropometry was created and validated. The results quantify changes in US child
      body dimensions since the 1970s. 

PMID- 25597930
TI  - Sleep disordered breathing risk in childhood cancer survivors: an exploratory
      study.
AB  - BACKGROUND: Sleep disordered breathing (SDB) is emerging as a significant health
      condition for children. The purpose of this study is to evaluate SDB symptoms in
      childhood cancer survivors and identify associations with quality of life (QOL)
      and psychological symptoms. PROCEDURE: A sample of 62 survivors aged 8-18 years
      were recruited during routine survivorship visits. All subjects and their parents
      completed questionnaires to evaluate sleep, QOL and psychological symptoms;
      scales included were: Pediatric Sleep Questionnaire, Sleep Disordered Breathing
      Subscale (PSQ-SDBS), Pediatric Quality of Life Inventory (PedsQL) and Depression
      Anxiety Stress Scale (DASS-21). Continuous data were used for all scales and a
      threshold score of >0.33 on the PSA-SDBS was used to identify risk of SDB. The
      relationships between measures of sleep and independent variables were examined
      using Pearson correlations and multiple linear regression models for significant
      associations. RESULTS: Of the 62 subjects enrolled, underlying diagnoses included
      29 leukemias, 30 solid tumors and 3 non-malignant diseases. Nineteen percent of
      subjects were identified as having SDB risk on the PSQ-SDBS. The lowest mean
      PedsQL subscale score for parent and child ratings were school QOL; Parent mean
      73(+/-SD 19) and Child mean 71(+/-SD 20). The severity of SDB per the PSQ was
      significantly associated with reduced total and school QOL which remained
      significant after adjusting for stress. CONCLUSIONS: Symptoms suggestive of SDB
      are common in childhood cancer survivors with negative implications for overall
      quality of life and school performance.

PMID- 25597932
TI  - Giant anal condyloma (giant condyloma acuminatum of anus) after allogeneic bone
      marrow transplantation associated with human papillomavirus: a case report.
AB  - INTRODUCTION: Condyloma acuminatum are caused by human papillomavirus. Giant
      condyloma acuminatum is a locally invasive, destructive, and large sized mass.
      Risk factors for the development of giant condyloma acuminatum include an
      immunodeficient state, such as human immunodeficiency virus infection, post-organ
      transplantation, or post-allogeneic bone marrow transplantation. However, reports
      of giant condyloma after bone marrow transplantation are extremely rare (0.3 to
      1.3%). The standard treatment for giant condyloma acuminatum is recommended as
      wide surgical resection due to its high rate of success and low rate of
      recurrence. CASE PRESENTATION: A 31-year-old Korean man presented to our hospital
      with anal discomfort for more than one month due to a protruding mass. He had a
      history of BCR-ABL-positive acute lymphoblastic leukemia and had undergone an
      allogenic stem cell transplantation. Gross findings revealed a large perianal
      cauliflower-like mass over 7cm in size with invasion of the anal orifice. He was
      diagnosed with giant anal condyloma occurring after an allogeneic bone marrow
      transplantation. However, we achieved successful treatment using a combination of
      topical podophyllin and cryotherapy and transanal surgical excision, followed by
      bleomycin irrigation. CONCLUSIONS: We report an extremely rare case of giant
      condyloma acuminatum of anus due to human papillomavirus type six in a patient
      with acute lymphoblastic leukemia following an allogeneic bone marrow
      transplantation. The tumor was successfully treated with a combination of topical
      podophyllin and cryotherapy and transanal surgical excision, followed by
      bleomycin irrigation.

PMID- 25597934
TI  - Cation-dependent intrinsic electrical conductivity in isostructural
      tetrathiafulvalene-based microporous metal-organic frameworks.
AB  - Isostructural metal-organic frameworks (MOFs) M2(TTFTB) (M = Mn, Co, Zn, and Cd;
      H4TTFTB = tetrathiafulvalene tetrabenzoate) exhibit a striking correlation
      between their single-crystal conductivities and the shortest S...S interaction
      defined by neighboring TTF cores, which inversely correlates with the ionic
      radius of the metal ions. The larger cations cause a pinching of the S...S
      contact, which is responsible for better orbital overlap between pz orbitals on
      neighboring S and C atoms. Density functional theory calculations show that these
      orbitals are critically involved in the valence band of these materials, such
      that modulation of the S...S distance has an important effect on band dispersion
      and, implicitly, on the conductivity. The Cd analogue, with the largest cation
      and shortest S...S contact, shows the largest electrical conductivity, sigma =
      2.86 (+/-0.53) * 10(-4) S/cm, which is also among the highest in microporous
      MOFs. These results describe the first demonstration of tunable intrinsic
      electrical conductivity in this class of materials and serve as a blueprint for
      controlling charge transport in MOFs with pi-stacked motifs. 

PMID- 25597933
TI  - A wireless neural recording system with a precision motorized microdrive for
      freely behaving animals.
AB  - The brain is composed of many different types of neurons. Therefore, analysis of
      brain activity with single-cell resolution could provide fundamental insights
      into brain mechanisms. However, the electrical signal of an individual neuron is
      very small, and precise isolation of single neuronal activity from moving
      subjects is still challenging. To measure single-unit signals in actively
      behaving states, establishment of technologies that enable fine control of
      electrode positioning and strict spike sorting is essential. To further apply
      such a single-cell recording approach to small brain areas in naturally behaving
      animals in large spaces or during social interaction, we developed a compact
      wireless recording system with a motorized microdrive. Wireless control of
      electrode placement facilitates the exploration of single neuronal activity
      without affecting animal behaviors. Because the system is equipped with a newly
      developed data-encoding program, the recorded data are readily compressed almost
      to theoretical limits and securely transmitted to a host computer. Brain activity
      can thereby be stably monitored in real time and further analyzed using online or
      offline spike sorting. Our wireless recording approach using a precision
      motorized microdrive will become a powerful tool for studying brain mechanisms
      underlying natural or social behaviors. 

PMID- 25597935
TI  - Stubborn nasojejunal feeding tube.

PMID- 25597936
TI  - Status of urological Kampo medicine: a narrative review and future vision.
AB  - Clinical evidence for traditional Japanese Kampo medicine has been provided by
      modern scientific methodologies. Indeed, more than 150 Kampo formulations have
      been approved for use as prescription drugs by the Ministry of Health, Labor and
      Welfare of Japan, and are widely used in daily medical practice. More than 10 of
      these formulations can be used for urological problems, especially in cases of
      lower urinary tract dysfunction. However, there are few opportunities to
      introduce urological Kampo medicines for worldwide use, and the status of
      urological Kampo medicine has not been reviewed yet. Here, we present a narrative
      review to introduce the current status of urological Kampo medicine in Japan.
      First, we introduce the essence of general Kampo medicine, including its history
      and current status in Japan. We focused of Sou-Sei-Sou-Koku, "promotion and
      inhibition network among the Five Elements," which is the central dogma of Kampo
      medicine. To present Kampo medicine as scientific medicine, neural cross-talk
      among pelvic organs is presented in comparison with Sou-Sei-Sou-Koku. Second, we
      list representative urological Kampo formulations used for lower urinary tract
      symptoms. Furthermore, we also discuss their roles in the urological field,
      including their position in Japanese clinical guidelines. Third, we propose the
      multi-organ targeting strategy using Kampo formulations as a future vision. Dai
      Ken-Chu-Tou (a common Kampo formulation for gastrointestinal problems and
      hypersensitivity to cold) is one candidate, and we present the results of a
      preliminary study using this Kampo medicine formulation. 

PMID- 25597937
TI  - Relationship between Exercise Parameters and Noninvasive Indices of Right
      Ventricular Function in Patients with Biventricular Circulation and Systemic
      Right Ventricle.
AB  - OBJECTIVES: In patients with systemic right ventricles (RVs) in a biventricular
      circulation, exercise capacity and RV function often deteriorate over time and
      echocardiographic assessment of systemic RV function is difficult. The purpose of
      this study was to examine the relationship between exercise capacity and RV
      function and to determine which noninvasive imaging parameters correlate most
      closely with exercise capacity. DESIGN: Patients with a systemic RV (D-loop
      transposition of the great arteries [TGA] after atrial switch procedure or
      physiologically "corrected" TGA) who underwent cardiopulmonary exercise testing
      (CPX) and noninvasive imaging (cardiac magnetic resonance [CMR] and
      echocardiography [echo]) within 1 year of CPX were identified. Regression
      analysis was used to evaluate the relationship between exercise variables and
      noninvasive indices of ventricular function. RESULTS: We identified 92 patients
      with 149 encounters (mean age 31.0 years, 61% men, 70% D-loop TGA) meeting
      inclusion criteria. Statistically significant correlations between % predicted
      peak oxygen uptake (%pVO2 ) and RV ejection fraction (EF) (r = 0.29, P = .0007),
      indexed RV end-systolic volume (r = -0.25, P = .002), and Tei index (r = -0.22, P
      = .03) were found. In patients without additional hemodynamically significant
      lesions, the correlations between %pVO2 and RV EF (r = 0.37, P = .0007) and the
      Tei index (r = -0.28, P = .03) strengthened and a correlation emerged between
      %pVO2 and dP/dtic (r = 0.31, P = .007). On multivariable analysis, Tei index was
      the only statistically significant correlate of %pVO2 (P = .04). CONCLUSIONS: In
      patients with systemic RVs in a biventricular circulation, CMR-derived RVEF and
      echo-derived Tei index correlate with %pVO2 . On multivariable analysis, the Tei
      index was the strongest predictor of peak %pVO2 response.

PMID- 25597939
TI  - The partnership for dengue control - a new global alliance for the prevention and
      control of dengue.

PMID- 25597938
TI  - Systems pharmacology of mifepristone (RU486) reveals its 47 hub targets and
      network: comprehensive analysis and pharmacological focus on FAK-Src-Paxillin
      complex.
AB  - Mifepristone (RU486), a synthetic steroid compound used as an abortifacient drug,
      has received considerable attention to its anticancer activity recently. To
      explore the possibility of using mifepristone as a cancer metastasis
      chemopreventive, we performed a systems pharmacology analysis of mifepristone
      related molecules in the present study. Data were collected by using Natural
      Language Processing (NLP) and 513 mifepristone-related genes were dug out and
      classified functionally using a gene ontology (GO) hierarchy, followed by KEGG
      pathway enrichment analysis. Potential signal pathways and targets involved in
      cancer were obtained by integrative network analysis. Total thirty-three proteins
      were involved in focal adhesion-the key signaling pathway associated with cancer
      metastasis. Molecular and cellular assays further demonstrated that mifepristone
      had the ability to prevent breast cancer cells from migration and interfere with
      their adhesion to endothelial cells. Moreover, mifepristone inhibited the
      expression of focal adhesion kinase (FAK), paxillin, and the formation of
      FAK/Src/Paxillin complex, which are correlated with cell adhesion and migration.
      This study set a good example to identify chemotherapeutic potential seamlessly
      from systems pharmacology to cellular pharmacology, and the revealed hub genes
      may be the promising targets for cancer metastasis chemoprevention. 

PMID- 25597941
TI  - Identification of protective linear B-cell epitopes on the subolesin/akirin
      orthologues of Ornithodoros spp. soft ticks.
AB  - Subolesin/akirin is a protective antigen that is highly conserved across
      hematophagous vector species and is therefore potentially useful for the
      development of a universal vaccine for vector control, including soft ticks.
      Recent results have shown that in Ornithodoros erraticus and O. moubata soft
      ticks, RNAi-mediated subolesin gene knockdown inhibits tick oviposition and
      fertility by more than 90%; however, vaccination with recombinant subolesins
      resulted in remarkably low protective efficacies (5-24.5% reduction in
      oviposition). Here we report that vaccination with subolesin recombinants induces
      non-protective antibodies mainly directed against immunodominant linear B-cell
      epitopes located on highly structured regions of the subolesin protein, probably
      unrelated to its biological activity, while leaving the unstructured/disordered
      regions unrecognized. Accordingly, for a new vaccine trial we designed four
      synthetic peptides (OE1, OE2, OM1 and OM2) from the unrecognized/disordered
      regions of the Ornithodoros subolesin sequences and coupled them to keyhole
      limpet haemocyanin (KLH). These KLH-peptide conjugates induced the synthesis of
      antibodies that recognized linear B-cell epitopes located on the unstructured
      loops of the subolesin protein and provided up to 70.1% and 83.1% vaccine
      efficacies in O. erraticus and O. moubata, respectively. These results show that
      the protective effect of subolesin-based vaccines is highly dependent on the
      particular epitope recognized by antibodies on the subolesin sequence and
      strongly suggest that the biological activity of subolesin is exerted through its
      unstructured regions. The results reported here contribute to our understanding
      of the mechanism of protection of subolesin-based vaccines and reveal novel
      protective peptides that could be included among the array of candidate antigens
      useful for developing anti-vector vaccines based on subolesin/akirin. 

PMID- 25597940
TI  - Expansion of syndromic vaccine preventable disease surveillance to include
      bacterial meningitis and Japanese encephalitis: evaluation of adapting polio and
      measles laboratory networks in Bangladesh, China and India, 2007-2008.
AB  - BACKGROUND: Surveillance for acute flaccid paralysis with laboratory confirmation
      has been a key strategy in the global polio eradication initiative, and the
      laboratory platform established for polio testing has been expanded in many
      countries to include surveillance for cases of febrile rash illness to identify
      measles and rubella cases. Vaccine-preventable disease surveillance is essential
      to detect outbreaks, define disease burden, guide vaccination strategies and
      assess immunization impact. Vaccines now exist to prevent Japanese encephalitis
      (JE) and some etiologies of bacterial meningitis. METHODS: We evaluated the
      feasibility of expanding polio-measles surveillance and laboratory networks to
      detect bacterial meningitis and JE, using surveillance for acute meningitis
      encephalitis syndrome in Bangladesh and China and acute encephalitis syndrome in
      India. We developed nine syndromic surveillance performance indicators based on
      international surveillance guidelines and calculated scores using supervisory
      visit reports, annual reports, and case-based surveillance data. RESULTS: Scores,
      variable by country and targeted disease, were highest for the presence of
      national guidelines, sustainability, training, availability of JE laboratory
      resources, and effectiveness of using polio-measles networks for JE surveillance.
      Scores for effectiveness of building on polio-measles networks for bacterial
      meningitis surveillance and specimen referral were the lowest, because of
      differences in specimens and techniques. CONCLUSIONS: Polio-measles surveillance
      and laboratory networks provided useful infrastructure for establishing syndromic
      surveillance and building capacity for JE diagnosis, but were less applicable for
      bacterial meningitis. Laboratory-supported surveillance for vaccine-preventable
      bacterial diseases will require substantial technical and financial support to
      enhance local diagnostic capacity.

PMID- 25597942
TI  - Vaccination with a live multi-gene deletion strain protects horses against
      virulent challenge with Streptococcus equi.
AB  - Strangles, caused by Streptococcus equi subspecies equi (S. equi) is one of the
      most frequently diagnosed infectious diseases of horses and there remains a
      significant need to develop new preventative vaccines. We generated a live
      vaccine strain of S. equi containing deletions in six genes: sagA, hasA, aroB,
      pyrC, seM and recA, which was administered to nine Welsh mountain ponies via the
      intramuscular route. Four vaccinated ponies developed adverse reactions following
      the first vaccination from which the live vaccine strain was isolated. Two of
      these ponies were withdrawn from the study and seven ponies received a second
      vaccination, one of which then developed an adverse reaction. Nine control ponies
      injected with culture media alone developed no adverse reactions. Following
      challenge with a virulent strain of S. equi, none of the seven vaccinated ponies
      had developed clinical signs of strangles eleven days post-challenge, compared to
      six of nine control ponies over the same period (P=0.0114). A lymph node abscess
      was identified in one of the seven vaccinated ponies at post-mortem examination,
      whilst all nine control ponies had at least one lymph node abscess (P=0.0009).
      Three of the six vaccinated ponies that were protected from strangles had not
      developed an adverse reaction following vaccination, suggesting that a better
      understanding of the pro-inflammatory responses to S. equi could lead to the
      development of a live attenuated vaccine against strangles that is safe for
      administration via intramuscular injection. 

PMID- 25597944
TI  - Trivalent pneumococcal protein recombinant vaccine protects against lethal
      Streptococcus pneumoniae pneumonia and correlates with phagocytosis by
      neutrophils during early pathogenesis.
AB  - OBJECTIVE: Due to the fact that current polysaccharide-based pneumococcal
      vaccines have limited serotype coverage, protein-based vaccine candidates have
      been sought for over a decade to replace or complement current vaccines. We
      previously reported that a trivalent Pneumococcal Protein recombinant Vaccine
      (PPrV), showed protection against pneumonia and sepsis in an infant murine model.
      Here we investigated immunological correlates of protection of PPrV in the same
      model. METHODS: C57BL/6J infant mice were intramuscularly vaccinated at age 1-3
      weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D
      (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin
      mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to
      PPrV components were measured, and mice were intranasally challenged with a
      lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial
      burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by
      granulocytes, and levels of cytokines and chemokines were determined at 6, 12,
      24, and 48h after challenge. RESULTS: PPrV vaccination conferred 83% protection
      against Spn challenge. Vaccinated mice had significantly elevated serum and lung
      antibody levels to three PPrV components. In the first stage of pathogenesis of
      Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn
      bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV
      vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1beta, and
      TFN-alpha, and other cytokines and chemokines (IL-12, IL-17, IFN-gamma, MIP-1b,
      MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden.
      CONCLUSION: Trivalent PPrV vaccination results in increased serum and lung
      antibody levels to the vaccine components, a reduction in Spn induced lethality,
      enhanced early clearance of Spn in lungs due to more rapid and thorough
      phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung
      inflammation and tissue damage.

PMID- 25597943
TI  - Enhanced protection against Rickettsia rickettsii infection in C3H/HeN mice by
      immunization with a combination of a recombinant adhesin rAdr2 and a protein
      fragment rOmpB-4 derived from outer membrane protein B.
AB  - BACKGROUND: Two surface proteins of Rickettsia rickettsii, outer membrane protein
      B (OmpB) and adhesion 2 (Adr2), have been recognized as protective antigens.
      Herein, the immunization with both OmpB and Adr2 was performed in mice so as to
      explore whether their combination could induce an enhanced immunoprotection
      against R. rickettsii infection. METHODS: C3H/HeN mice were immunized with
      recombinant protein rAdr2 or/and rOmp-4, a fragment derived from OmpB, and then
      mice were challenged with R. rickettsii. After which rickettsial loads in mice
      were measured by quantitative PCR. The specific antibodies in mouse sera were
      determined by ELISA and antigen-specific cytokines secretion by mouse T cells
      were analyzed in vitro. RESULTS: After challenge with R. rickettsii, the mice
      immunized with rAdr2 or/and rOmpB-4 had significant lower rickettsial load in
      livers, spleens, or lungs compared to PBS mock-immunized mice. Particularly, the
      load in lungs of mice immunized with both rAdr2 and rOmpB-4 was significantly
      lower than that with either of them. High levels of specific antibodies were
      detected in sera from mice immunized with rAdr2 or/and rOmpB-4, but the ratios of
      specific IgG2a to IgG1 induced by their combination were significantly higher
      than that by either rAdr2 or rOmpB-4. Following stimulation with rAdr2 or/and
      rOmpB-4, the INF-gamma secreted by CD4(+) T cells from infected mice was
      significantly higher than that by cognate cells from uninfected mice. And the TNF
      alpha secreted by CD4(+) or CD8(+) T cells from infected mice was markedly
      greater than that by cognate cells from uninfected mice after stimulation by
      their combination but not either of them. CONCLUSION: The combination of rAdr2
      and rOmpB-4 conferred an enhanced protection against R. rickettsii infection in
      mice, which was mainly dependent on a stronger Th1-oriented immunoresponse with
      greater INF-gamma and TNF-alpha secretion by antigen-specific T cells and
      specific IgG2a elicited by the combination.

PMID- 25597945
TI  - Human papillomavirus vaccination: assessing knowledge, attitudes, and intentions
      of college female students in Lebanon, a developing country.
AB  - Human papillomavirus (HPV) infection is a common cause for genital warts and
      cervical cancer. Developing countries in the Middle East such as Lebanon are
      traditionally considered to be conservative societies with low incidence of
      sexually transmitted infections. However, nowadays, there is an unexpected
      increase in the incidence of HPV infections among Middle Eastern females. Thus,
      the objective of this study is to assess the behavioral perceptions of HPV
      vaccination among female students attending an academic institution in Lebanon.
      This cross-sectional study invited 512 students to complete a self-administered
      questionnaire that assessed the knowledge, attitudes, and intentions towards HPV
      vaccination. Data analysis included the calculation of knowledge scores ranging
      from 0 to 100, attitude scores ranging from most positive (1) to most negative
      (5), and intention scores ranging from lowest intention (0) to highest intention
      (10). With a response rate of n=215 (42%), 36.5% never heard of the vaccine
      before, and only 16.5% were already HPV vaccinated. The median knowledge score of
      52.7% +/- 1.71 reflects poor to moderate knowledge. Still, the median attitude
      score of 2.47 +/- 0.05 shows a general positive attitude towards HPV vaccination
      where most of the participants agreed that female college students in Lebanon
      have a good chance of contracting HPV (62.1%) and that all gynecologists should
      recommend the vaccine (76.0%). Students in graduate programs, health related
      majors, and those who are vaccinated had significantly higher knowledge scores
      compared with students in undergraduate programs, non-health related majors, and
      HPV non-vaccinated students, respectively. Finally, the survey helped in
      increasing the intention to obtain HPV vaccine as the intention score increased
      significantly from 5.24 +/- 0.27 before the students went through the survey to
      6.98 +/- 0.22 after the students completed the survey. Our study highlights the
      importance of offering guidance to female college students about HPV and its
      vaccination in developing countries where the incidence of sexually transmitted
      infections is on the rise.

PMID- 25597947
TI  - Short-term high altitude exposure at 3454 m is well tolerated in patients with
      stable heart failure.
AB  - AIMS: High altitude exposure for the purpose of tourism is very popular in
      mountainous regions and is considered to be safe for patients with stable CAD and
      preserved LV function. The purpose of this study was to evaluate the haemodynamic
      response to exercise and electrical stability by Holter monitoring in patients
      with chronic heart failure (HF) and an EF <40%. METHODS AND RESULTS: We studied
      29 HF patients with a peak VO2 >50% of the predicted (25 men, age 60.0 +/- 8.9
      years, EF 28.8 +/- 5.4%) at 540 and 3454 m after an ascent using public
      transport. Assessments of exercise capacity (cardiopulmonary exercise test),
      haemodynamic response (inert gas rebreathing system), and susceptibility to
      arrhythmias (Holter ECG recording) were performed. None of the patients (19 with
      ischaemic heart disease, 11 with an implantable cardioverter defibrillator) had
      to return prematurely to the lowland site. Two patients presented symptoms of
      mild mountain sickness, and one patient developed a self-limited ventricular
      tachycardia during maximal exercise at high altitude. Mean peak VO2 at the
      lowland site was 18.5 +/- 3.6 mL/min/kg and decreased by 22.2% (P < 0.001) at
      high altitude. Mean resting heart rate increased from 74.3 +/- 12.3 to 83.3 +/-
      13.4 b.p.m., P < 0.001. No statistically significant difference in premature
      ventricular contractions (92 +/- 150/h at 540 m vs. 111 +/- 196/h at 3454 m, P =
      0.284) was noted. CONCLUSION: Patients with stable chronic HF and a peak VO2 >50%
      of the predicted tolerate a short exposure to an altitude of 3454 m well, even
      during exercise. However, it cannot be excluded that the susceptibility to
      ventricular tachyarrhythmias during exercise is increased in some subjects.

PMID- 25597948
TI  - The pep4 gene encoding proteinase A is involved in dimorphism and pathogenesis of
      Ustilago maydis.
AB  - Vacuole proteases have important functions in different physiological processes
      in fungi. Taking this aspect into consideration, and as a continuation of our
      studies on the analysis of the proteolytic system of Ustilago maydis, a
      phytopathogenic member of the Basidiomycota, we have analysed the role of the
      pep4 gene encoding the vacuolar acid proteinase PrA in the pathogenesis and
      morphogenesis of the fungus. After confirmation of the location of the protease
      in the vacuole using fluorescent probes, we obtained deletion mutants of the gene
      in sexually compatible strains of U. maydis (FB1 and FB2), and analysed their
      phenotypes. It was observed that the yeast to mycelium dimorphic transition
      induced by a pH change in the medium, or the use of a fatty acid as sole carbon
      source, was severely reduced in Deltapep4 mutants. In addition, the virulence of
      the mutants in maize seedlings was reduced, as revealed by the lower proportion
      of plants infected and the reduction in size of the tumours induced by the
      pathogen, when compared with wild-type strains. All of these phenotypic
      alterations were reversed by complementation of the mutant strains with the wild
      type gene. These results provide evidence of the importance of the pep4 gene for
      the morphogenesis and virulence of U. maydis.

PMID- 25597946
TI  - A survey of advancements in nucleic acid-based logic gates and computing for
      applications in biotechnology and biomedicine.
AB  - Nucleic acid-based logic devices were first introduced in 1994. Since then,
      science has seen the emergence of new logic systems for mimicking mathematical
      functions, diagnosing disease and even imitating biological systems. The unique
      features of nucleic acids, such as facile and high-throughput synthesis, Watson
      Crick complementary base pairing, and predictable structures, together with the
      aid of programming design, have led to the widespread applications of nucleic
      acids (NA) for logic gate and computing in biotechnology and biomedicine. In this
      feature article, the development of in vitro NA logic systems will be discussed,
      as well as the expansion of such systems using various input molecules for
      potential cellular, or even in vivo, applications. 

PMID- 25597950
TI  - Purine metabolism gene deregulation in Parkinson's disease.
AB  - AIMS: To explore alterations in the expression of genes encoding enzymes involved
      in purine metabolism in Parkinson's disease (PD) brains as purines are the core
      of the DNA, RNA, nucleosides and nucleotides which participate in a wide variety
      of crucial metabolic pathways. METHODS: Analysis of mRNA using real-time
      quantitative PCR of 22 genes involved in purine metabolism in the substantia
      nigra, putamen and cerebral cortex area 8 in PD at different stages of disease
      progression, and localization of selected purine metabolism-related enzymes with
      immunohistochemistry. RESULTS: Reduced expression of adenylate kinase 2 (AKA2),
      AK3, AK4, adenine phosphoribosyltransferase, ectonucleoside triphosphate
      diphosphohydrolase 1 (ENTPD1), ENTPD3, nonmetastatic cells 3, nucleoside
      diphosphatese kinase 3 (NME1), NME7 and purine nucleoside phosphorylase 1 (PNP1)
      mRNA in the substantia nigra at stages 3-6; up-regulation of ADA mRNA in the
      frontal cortex area 8 at stages 3-4 and of AK1, AK5, NME4, NME5, NME6, 5'
      nucleotidase (NT5E), PNP1 and prune homolog Drosophila at stages 5-6. There is no
      modification in the expression of these genes in the putamen at stages 3-5.
      CONCLUSIONS: Gene down-regulation in the substantia nigra may be interpreted as a
      consequence of dopaminergic cell death as ENTPD3, NME1, NME7, AK1 and PNP1 are
      mainly expressed in neurons. Yet ENTPD1 and NT5E, also down-regulated in the
      substantia nigra, are expressed in astrocytes, probably pericytes and microglia,
      respectively. In contrast, gene up-regulation in the frontal cortex area 8 at
      advanced stages of the disease suggests a primary manifestation or a compensation
      of altered purine metabolism in this region.

PMID- 25597949
TI  - Modulation of the spleen transcriptome in domestic turkey (Meleagris gallopavo)
      in response to aflatoxin B1 and probiotics.
AB  - Poultry are highly susceptible to the immunotoxic effects of the food-borne
      mycotoxin aflatoxin B1 (AFB1). Exposure impairs cell-mediated and humoral
      immunity, limits vaccine efficacy, and increases the incidence of costly
      secondary infections. We investigated the molecular mechanisms of AFB1
      immunotoxicity and the ability of a Lactobacillus-based probiotic to protect
      against aflatoxicosis in the domestic turkey (Meleagris gallopavo). The spleen
      transcriptome was examined by RNA sequencing (RNA-seq) of 12 individuals
      representing four treatment groups. Sequences (6.9 Gb) were de novo assembled to
      produce over 270,000 predicted transcripts and transcript fragments. Differential
      expression analysis identified 982 transcripts with statistical significance in
      at least one comparison between treatment groups. Transcripts with known immune
      functions comprised 27.6 % of significant expression changes in the AFB1-exposed
      group. Short exposure to AFB1 suppressed innate immune transcripts, especially
      from antimicrobial genes, but increased the expression of transcripts from E3
      ubiquitin-protein ligase CBL-B and multiple interleukin-2 response genes. Up
      regulation of transcripts from lymphotactin, granzyme A, and perforin 1 could
      indicate either increased cytotoxic potential or activation-induced cell death in
      the spleen during aflatoxicosis. Supplementation with probiotics was found to
      ameliorate AFB1-induced expression changes for multiple transcripts from
      antimicrobial and IL-2-response genes. However, probiotics had an overall
      suppressive effect on immune-related transcripts. 

PMID- 25597951
TI  - The effect of 1,25 dihydroxyvitamin D3 treatment on the mRNA levels of beta
      catenin target genes in mice with colonic inactivation of both APC alleles.
AB  - In colon cancer, adenomatous polyposis coli (APC) inactivating gene mutations
      increase nuclear beta-catenin levels and stimulate proliferation. In vitro, 1,25
      dihydroxyvitamin D (1,25(OH)2D), suppresses beta-catenin-mediated gene
      transcription by inducing vitamin D receptor (VDR)-beta-catenin interactions. We
      examined whether acute treatment with 1,25(OH)2D could suppress beta-catenin
      mediated gene transcription in the hyperplastic colonic lesions of mice with
      colon-specific deletion of both APC gene alleles (CAC; APC(Delta580/Delta580)).
      At four weeks of age, CAC; APC(Delta580/Delta580) and control mice were injected
      with vehicle or 1,25(OH)2D (1MUg/kg body weight) once a day for three days and
      then killed six hours after the last injection. mRNA levels of beta-catenin
      target genes were elevated in the colon of CAC; APC(Delta580/Delta580) mice.
      1,25(OH)2D increased 25 hydroxyvitamin D-24 hydroxylase mRNA levels in the colon
      of CAC; APC(Delta580/Delta580) and control mice indicating the treatments
      activated the VDR. However, 1,25(OH)2D had no effect on either beta-catenin
      target gene mRNA levels or the proliferation index in CAC; APC(Delta580/Delta580)
      or control mice. VDR mRNA and protein levels were lower (-65% and -90%) in the
      colon of CAC; APC(Delta580/Delta580) mice compared to control mice, suggesting
      loss of colon responsiveness to vitamin D. Consistent with this, vitamin D
      induced expression of transient receptor potential cation channel, subfamily V,
      member 6 mRNA was reduced in the colon of CAC; APC(Delta580/Delta580) mice. Our
      data show that short term exposure to 1,25(OH)2D does not suppress colonic beta
      catenin signaling in vivo. This article is part of a special issue entitled '17th
      Vitamin D Workshop'. 

PMID- 25597953
TI  - Vertical ordering sensitivity of solid supported DPPC membrane to alamethicin and
      the related loss of cell viability.
AB  - BACKGROUND: Experimental studies of antimicrobial peptides interacting with lipid
      membranes recently attracted growing interest due to their numerous biomedical
      applications. However, the influence of such peptides on the structural
      organisation of lipid membranes in connection with the actual cell response still
      remains an elusive issue. METHODS: X-ray diffraction was employed on detecting
      the sensitivity of the periodical spacing of dipalmitoyl-phosphatidyl-choline
      stacked as solid-supported bilayers to the presence of varying amounts of the
      peptide alamethicin in a wide range of peptide-to-lipid molar ratios. These
      results were then correlated with the effects of alamethicin on biological
      membranes in vitro as observed by optical microscopy and microculture tetrazolium
      assay on the tumour cells HeLa to provide a comprehensive and quantitative
      analysis of these effects, based on a dose-response relationship. RESULTS: The
      experiments allowed correlating the periodical spacing and the peptide-to-lipid
      molar ratio on alamethicin-dipalmitoyl-phosphatidyl-choline samples. Two
      different trends of periodical spacing vs. peptide-to-lipid molar ratio clearly
      appeared at low and high hydration levels, showing intriguing non-linear
      profiles. Unexpected correspondences were observed between the peptide-to-lipid
      molar ratio range where the changes in dipalmitoyl-phosphatidyl-choline structure
      occur and the alamethicin doses which alter the viability and the plasma membrane
      morphology of HeLa. CONCLUSIONS: Alamethicin might induce either mechanical or
      phase changes on dipalmitoyl-phosphatidyl-choline bilayers. Such easily
      accessible ordering information was well-calibrated to predict the alamethicin
      doses necessary to trigger cell death through plasma membrane alterations.
      GENERAL SIGNIFICANCE: This benchmark combined study may be valuable to predict
      bioeffects of several antimicrobial peptides of biomedical relevance.

PMID- 25597954
TI  - Chip physically interacts with Notch and their stoichiometry is critical for
      Notch function in wing development and cell proliferation in Drosophila.
AB  - BACKGROUND: Notch signaling plays a fundamental role both in metazoan cell fate
      determination and in the establishment of distinct developmental cell lineages.
      In a yeast two-hybrid screen, we identified Chip as a binding partner of Notch.
      Thus, we investigated the functional significance of Notch and Chip interactions.
      METHODS: Co-immunoprecipitation and GST pull-down experiments confirmed the
      physical interaction between Notch and Chip. Immunostaining revealed that Chip
      and Notch-intracellular domain (Notch-ICD) co-localized in cell nuclei. Loss-of
      function and gain-of-function analyses of Chip were carried out using FLP/FRT and
      GAL4-UAS systems, respectively. Immunostaining and real-time PCR were performed
      to analyze the role of Chip on Notch-induced cell proliferation. RESULTS: Here,
      we report transcriptional cofactor Chip as a novel binding partner of Notch. Chip
      and Notch also showed strong genetic interactions, and Chip mutant clones in the
      dorsal compartment induced ectopic wing margins by ectopic expression of Notch
      and its targets, Wg and Cut. Our analyses revealed that stoichiometry of Notch
      and Chip is critical at the dorso-ventral (DV) boundary for wing margin
      formation. In addition, overexpression of Chip can rescue Notch-induced cell
      proliferation in larval imaginal discs. CONCLUSIONS: Our results indicate that
      Notch function in the DV boundary area is presumably dependent on Notch-Chip
      heterodimer formation. In addition, overexpression of Chip can rescue Notch
      induced cell proliferation, presumably through titration of overexpressed Notch
      ICD by excess Chip molecules. GENERAL SIGNIFICANCE: The present study reveals
      that Chip is a novel interacting partner of Notch and it plays a major role in
      Notch-induced DV margin formation and cell proliferation.

PMID- 25597956
TI  - A new asymmetric directional microphone algorithm with automatic mode-switching
      ability for binaural hearing support devices.
AB  - For hearing support devices, it is important to minimize the negative effect of
      ambient noises for speech recognition but also, at the same time, supply natural
      ambient sounds to the hearing-impaired person. However, conventional fixed
      bilateral asymmetric directional microphone (DM) algorithms cannot perform in
      such a way when the DM-mode device and a dominant noise (DN) source are placed on
      the same lateral hemisphere. In this study, a new binaural asymmetric DM
      algorithm that can overcome the defects of conventional algorithms is proposed.
      The proposed algorithm can estimate the position of a specific DN in the 90
      degrees -270 degrees  range and switch directional- and omnidirectional-mode
      devices automatically if the DM-mode device and the DN are placed in opposite
      lateral hemispheres. Computer simulation and KEMAR mannequin recording tests
      demonstrated that the performance of the conventional algorithm deteriorated when
      the DM-mode device and the DN were placed in the opposite hemisphere; in
      contrast, the performance of the proposed algorithm was consistently maintained
      regardless of directional variations in the DN. Based on these experimental
      results, the proposed algorithm may be able to improve speech quality and
      intelligibility for hearing-impaired persons who have similar degrees of hearing
      impairment in both ears. 

PMID- 25597955
TI  - Metal-immobilized magnetic nanoparticles for cytochrome C purification from rat
      liver.
AB  - Cu(2+) -immobilized magnetic poly(hydroxyethylmethacrylate-N-methacryloyl-(l)
      histidinemethylester) (mPHEMAH) nanoparticles were prepared by surfactant-free
      emulsion polymerization for cytochrome C (cyt C) purification from rat liver.
      Elemental analysis, atomic force microscopy, zeta sizer, and vibrating sample
      magnetometer were used to characterize mPHEMAH nanoparticles. In addition to
      these characterization steps, surface area, average particle size, and size
      distribution of mPHEMAH nanoparticles were determined. Quantity of immobilized
      Cu(2+) was measured using atomic absorption spectrophotometry. N-Methacryloyl-(l)
      histidinemethylester and Cu(2+) content of mPHEMAH nanoparticles were 0.18 mmol/g
      polymer and 0.11 mmol/g polymer, respectively. Specific surface area of Cu(2+) 
      immobilized mPHEMAH nanoparticles was 1180 m(2) /g. Effect of initial cyt C
      concentration, pH, temperature, and ionic strength on cyt C adsorption onto
      Cu(2+) -immobilized mPHEMAH nanoparticles was investigated. Maximum cyt C
      adsorption capacity of Cu(2+) -immobilized mPHEMAH nanoparticles was 311.9 mg/g
      polymer. Maximum adsorption was obtained at pH 8.0 and 4  degrees C. Cu(2+) 
      immobilized mPHEMAH nanoparticles were used ten times with 4.1% decrease in
      adsorption capacity. In the last stage, Cu(2+) -immobilized mPHEMAH nanoparticles
      were used to purify cyt C from rat liver tissue, and the purity of desorbed
      fractions was controlled by SDS-PAGE. 

PMID- 25597952
TI  - Effects of supplemental vitamin D and calcium on normal colon tissue and
      circulating biomarkers of risk for colorectal neoplasms.
AB  - This brief review, based on an invited presentation at the 17th Workshop on
      Vitamin D, is to summarize a line of the author's research that has been directed
      at the intertwined missions of clarifying and/or developing vitamin D and calcium
      as preventive agents against colorectal cancer in humans, understanding the
      mechanisms by which these agents may reduce risk for the disease, and developing
      'treatable' biomarkers of risk for colorectal cancer. The biological plausibility
      and observational and clinical trial evidence for vitamin D and calcium in
      reducing risk for colorectal neoplasms, the development of pre-neoplastic
      biomarkers of risk for colorectal neoplasms, and the clinical trial findings from
      the author's research group on the efficacy of vitamin D and calcium in
      modulating these biomarkers are summarized. Regarding the latter, we tested the
      efficacy of 800 IU (20MUg) of vitamin D3 and 2.0g of calcium daily, alone and
      combined vs. placebo over 6 months on modulating normal colon tissue and
      circulating hypothesis-based biomarkers of risk for colorectal neoplasms in a
      randomized, double-blind, placebo-controlled, 2*2 factorial design clinical trial
      (n=92). The tissue-based biomarkers were measured in biopsies of normal-appearing
      rectal mucosa using immunohistochemistry with quantitative image analysis, and a
      panel of circulating inflammation markers was measured using enzyme-linked
      immunoassays (ELISA). Statistically significant proportional tissue increases in
      the vitamin D group relative to the placebo group were found in bax (51%), p21
      (141%), APC (48%), E-cadherin (78%), MSH2 (179%), the CaSR (39%), and CYP27B1
      (159%). In blood, there was a 77% statistically significant decrease in a summary
      inflammation z-score. The findings for calcium were similar to those for vitamin
      D. These findings indicate that supplemental vitamin D3 or calcium can favorably
      modulate multiple normal colon tissue and circulating hypothesis-based biomarkers
      of risk for colorectal neoplasms in sporadic colorectal adenoma patients. This
      article is part of a Special Issue entitled '17th Vitamin D Workshop'. 

PMID- 25597957
TI  - Evidence Aid approach to gap analysis and priority setting of questions for
      systematic reviews in disasters.
AB  - This article is based on a presentation at the Evidence Aid Symposium, on 20
      September 2014, at Hyderabad, India. Ten years after the Indian Ocean Tsunami,
      Evidence Aid and it parters and other humanitarian stakeholders met to update
      about Evidence Aid work and discussed it future. The Evidence Aid approach to
      fill in the gap on the production and use of evidence in disater sector and other
      humanitarian health emergencies was widely discussed. Iterative approach to
      prioritise evidence reinforced Evidence Aid principle of independacy and a
      coordinated international orgasisation. The generation of 30 research questions
      during the prioritisation process contitute the first big step for Evidence Aid
      to become a one stop shop for the seach evidence on the effectiveness of
      interventions in disasters. 

PMID- 25597958
TI  - Analysis of gene expression profiles reveals the regulatory network of cold
      inducible RNA-binding protein mediating the growth of BHK-21 cells.
AB  - Cold-inducible RNA-binding protein (Cirp), the first cold-shock protein
      identified in mammals, is a sensor protein whose expression increases in response
      to stress. Recent reports have shown that Cirp is involved in cell proliferation,
      development, circadian modulation under physiological conditions, and tumor
      formation and progression. However, the molecular mechanisms underlying the
      activities of Cirp in the mammalian kidney cells remain unclear. In this study,
      we constructed BHK-21cells overexpressing Cirp (Cirp + BHK-21) knockdown BHK-21
      cells (Cirp - BHK-21) to investigate the function of Cirp in cell proliferation.
      We analyzed the gene expression of Cirp - BHK-21 cells using genome-wide
      expression microarrays to explore the molecular mechanism of Cirp action. We
      found that (1) Cirp overexpression significantly enhanced cell proliferation,
      whereas Cirp knockdown dramatically reduced cell proliferation, suggesting that
      Cirp is a positive regulator of BHK-21 cell proliferation. (2) Differentially
      expressed genes in Cirp - BHK-21 and control cells were shown to be involved in
      many biological processes. (3) Pathway analysis showed that five enriched
      pathways, namely, Focal adhesion, Mapk, Wnt, Apoptosis, and Cancer-related
      signaling pathways, were identified as central pathway networks regulated by
      Cirp. These results can provide new insights into the molecular mechanisms of
      Cirp function. 

PMID- 25597960
TI  - Finite element analysis of the percutaneous coronary intervention in a coronary
      bifurcation.
AB  - PURPOSE: The paper presents the process of numerical modeling and simulation of
      balloon angioplasty of the coronary artery using Finite Element Method. METHODS:
      The authors focused on the issue of applying adequate pressure in an arterial
      tissue during the post-dilatation process in the "kissing balloon" stenting
      technique applied to patients with bifurcation stenosis. Despite great progress
      in the field of interventional cardiology, angioplasty in bifurcations still
      belongs to the most difficult interventions, generally being less effective and
      more risky than in the cases of straight stenosis. RESULTS: During the modeling
      procedures and further simulations, the authors focused on mutual cooperation of
      non-compliant angioplasty balloons and the coronary artery. The other goal was to
      develop a sufficiently accurate model of the coronary artery fragment, including
      its bifurcation and angioplasty balloons; however, it was decided to ignore the
      modeling of coronary stents. CONCLUSIONS: The issue undertaken is considered as
      relatively complicated and complex but, in the authors' opinion, the
      implementation of advanced computer aided engineering techniques may, in this
      case, answer several important questions without the need of performing costly
      and aggravating in vivo tests.

PMID- 25597959
TI  - The molecular mechanism underlying the induction of hepatic MRP3 expression and
      function by omeprazole.
AB  - Previous work has indicated that there is increased protein expression of
      multidrug resistance-associated protein 3 (MRP3) in the liver samples of patients
      treated with omeprazole compared with those who were not. However, evidence is
      still lacking to show the mechanisms underlying that induction. This study aimed
      to assess changes in the fold-induction of MRP3 mRNA and protein expression over
      controls in omeprazole-treated HepG2 cells after transient transfection of human
      MRP3 siRNA, or after pretreatment with actinomycin D (Act-D). Furthermore, MRP3
      siRNA knock-down or MRP-specific inhibition (indomethacin) was used to determine
      whether the MRP3 protein induced by omeprazole possessed an enhanced efflux
      transport. The results demonstrated that omeprazole induced MRP3 mRNA and protein
      expression in a concentration- and time-dependent manner. Moreover, that
      induction was almost completely abolished by the addition of human MRP3 siRNA and
      also by pretreatment with Act-D, respectively. In addition, the decay rate of
      MRP3 mRNA in vehicle- and omeprazole-treated cells was similar in the presence of
      Act-D, suggesting transcriptional up-regulation of MRP3 mRNA expression by
      omeprazole. Most importantly, omeprazole induced MRP3 efflux transport activity,
      as measured by the 5-carboxyfluorescein assay in the absence and presence of
      human MRP3 siRNA or indomethacin. It is concluded that omeprazole can induce MRP3
      mRNA and protein expression and enhance MRP3 efflux transport activity through
      transcriptional up-regulation, and that omeprazole can also induce other MRP
      transporters.

PMID- 25597961
TI  - Two successive C2 losses from C86 fullerene upon chlorination with the formation
      of non-classical C84Cl30 and C82Cl30.
AB  - High-temperature chlorination of a fullerene C86 with VCl4 afforded non-classical
      C84Cl30 and C82Cl30 containing one and two heptagons, respectively, in the carbon
      cages. Two types of C2 losses, which differ in the final arrangements of separate
      or fused pentagons, can occur successively in either order, producing rather flat
      or concave regions on the shrinked carbon cage. In the chlorination-promoted
      skeletal transformation of C86 (isomer no. 16) with the loss(es) of C2 units, the
      structures of the starting, intermediate, and final compounds were all revealed
      unambiguously by X-ray single crystal diffraction.

PMID- 25597962
TI  - Addressing unmet need by expanding access to safe second trimester medical
      abortion services in Ethiopia, 2010-2014.

PMID- 25597963
TI  - Ex vivo electrical impedance measurements on excised hepatic tissue from human
      patients with metastatic colorectal cancer.
AB  - Point-wise ex vivo electrical impedance spectroscopy measurements were conducted
      on excised hepatic tissue from human patients with metastatic colorectal cancer
      using a linear four-electrode impedance probe. This study of 132 measurements
      from 10 colorectal cancer patients, the largest to date, reports that the
      equivalent electrical conductivity for tumor tissue is significantly higher than
      normal tissue (p < 0.01), ranging from 2-5 times greater over the measured
      frequency range of 100 Hz-1 MHz. Difference in tissue electrical permittivity is
      also found to be statistically significant across most frequencies. Furthermore,
      the complex impedance is also reported for both normal and tumor tissue.
      Consistent with trends for tissue electrical conductivity, normal tissue has a
      significantly higher impedance than tumor tissue (p < 0.01), as well as a higher
      net capacitive phase shift (33 degrees  for normal liver tissue in contrast to 10
      degrees  for tumor tissue). 

PMID- 25597964
TI  - Bilayer mass transport model for determining swelling and diffusion in coated,
      ultrathin membranes.
AB  - Water transport and swelling properties of an ultrathin, selective polyamide
      layer with a hydrophilic polymer coating, i.e., a polymer bilayer, are studied
      using quartz crystal microbalance with dissipation (QCM-D). Specifically, QCM-D
      is used to measure the dynamic and equilibrium change in mass in a series of
      differential sorption experiments to determine the dependence of the apparent
      diffusion coefficient and equilibrium swelling of the bilayer as a function of
      the water vapor activity. To determine transport properties specific to the
      polyamide layer, sorption kinetics of the bilayer was modeled with a bilayer mass
      transport model. The swelling and water diffusion coefficients are interpreted
      according to the Painter-Shenoy polymer network swelling model and the solution
      diffusion model, respectively. 

PMID- 25597965
TI  - Limitations of on-site dairy farm regulatory debits as milk quality predictors.
AB  - In the United States, compliance with grade A raw fluid milk regulatory standards
      is assessed via laboratory milk quality testing and by on-site inspection of
      producers (farms). This study evaluated the correlation between on-site survey
      debits being marked and somatic cell count (SCC) or standard plate count (SPC)
      laboratory results for 1,301 Wisconsin grade A dairy farms in 2012. Debits
      recorded on the survey form were tested as predictors of laboratory results
      utilizing ordinary least squares regression to determine if results of the
      current method for on-site evaluation of grade A dairy farms accurately predict
      SCC and SPC test results. Such a correlation may indicate that current methods of
      on-site inspection serve the primary intended purpose of assuring availability of
      high-quality milk. A model for predicting SCC was estimated using ordinary least
      squares regression methods. Step-wise selected regressors of grouped debit items
      were able to predict SCC levels with some degree of accuracy (adjusted
      R2=0.1432). Specific debit items, seasonality, and farm size were the best
      predictors of SCC levels. The SPC data presented an analytical challenge because
      over 75% of the SPC observations were at or below a 25,000 cfu/mL threshold but
      were recorded by testing laboratories as at the threshold value. This classic
      censoring problem necessitated the use of a Tobit regression approach. Even with
      this approach, prediction of SPC values based on on-site survey criteria was much
      less successful (adjusted R2=0.034) and provided little support for the on-site
      survey system as a way to inform farmers about making improvements that would
      improve SPC. The lower level of correlation with SPC may indicate that factors
      affecting SPC are more varied and differ from those affecting SCC. Further,
      unobserved deficiencies in postmilking handling and storage sanitation could
      enhance bacterial growth and increase SPC, whereas postmilking sanitation will
      have no effect on SCC because somatic cells do not reproduce in stored milk.
      Results suggest that close examination, and perhaps redefinition, of survey
      debits, along with making the survey coincident with SCC and SPC sampling, could
      make the on-site survey a better tool for ensuring availability of high-quality
      milk.

PMID- 25597966
TI  - Cow-to-cow variation in fibroblast response to a toll-like receptor 2/6 agonist
      and its relation to mastitis caused by intramammary challenge with Staphylococcus
      aureus.
AB  - Staphylococcus aureus is a common cause of chronic mammary gland infections in
      dairy cattle. However, the inflammatory response and duration of infection
      following pathogen exposure is variable between individual animals. To
      investigate interanimal differences in immune response, dermal fibroblast
      cultures were established from skin biopsies collected from 50 early lactation
      Holstein cows. The fibroblasts ability to produce IL-8 in response to a 24-h
      treatment with a synthetic toll-like receptor 2/6 agonist (Pam2CSK4) was used to
      assign a response phenotype to the animals. Five high-responding and 5 low
      responding animals were then selected for an intramammary challenge with S.
      aureus to evaluate differences in the inflammatory response, chronicity of
      infection, and development of antibodies to the pathogen. All animals exhibited
      clinical symptoms of mastitis at 24h postchallenge. Animals previously classified
      as high responders experienced a greater inflammatory response characterized by
      elevated levels of milk somatic cell count, IL-8, and BSA following the challenge
      compared with low responders. In addition, antibodies toward the challenge strain
      of S. aureus reached higher levels in whey from the challenged gland of high
      responders compared with low responders. Despite the antibody response, all 5
      high responders were chronically infected for the 6-wk duration of the study,
      whereas 2 of the low responders cleared the infection, although 1 of these did
      become reinfected. The observed differences between animals classified as low and
      high responders based on their fibroblast responsiveness suggests that this cell
      type can be used to further examine the causes of interanimal variation in
      response to mammary infection. 

PMID- 25597967
TI  - Plane of nutrition influences the performance, innate leukocyte responses, and
      resistance to an oral Salmonella enterica serotype Typhimurium challenge in
      Jersey calves.
AB  - Two experiments investigated how plane of nutrition influences performance,
      leukocyte responses, and resistance to an oral Salmonella enterica serotype
      Typhimurium challenge. In experiment 1, 46 (2+/-1 d of age) calves were randomly
      assigned to 2 diets: a low (LPN; n=23) and high plane of nutrition (HPN; n=23).
      The LPN calves were fed 409 g/d of dry matter (DM) of a 20% crude protein and 20%
      fat milk replacer, whereas HPN calves were fed 610 and 735 g/d of DM of a 28%
      crude protein and 25% fat milk replacer during wk 1 and 2 to 6, respectively. In
      experiment 2, 20 bull calves (LPN; n=11 and HPN; n=9) were orally challenged on d
      80 with 1.5*10(7) cfu of Salmonella Typhimurium (ATCC #14028). The HPN calves had
      a greater incidence (87.5 vs. 45.5%) and duration of days with high fecal scores
      (5.5 vs. 3.5 d). The LPN calves had greater neutrophil surface expression of L
      selectin on d 7, 21, and 42. Following the Salmonella Typhimurium challenge, calf
      starter DM intake was greater among the HPN calves. The percentage of neutrophils
      producing an oxidative burst was also greater among HPN calves on d 1 to 5 after
      the challenge. Similarly, the intensity of the oxidative burst tended to be
      greater among the HPN calves on d 2 and 3 postchallenge. The secretion of tumor
      necrosis factor-alpha from whole-blood cultures stimulated with
      lipopolysaccharide tended to be greater on d 1 and was greater on d 5 and 6 among
      HPN calves. The median ranks of haptoglobin concentrations were greater and
      plasma zinc concentrations tended to be decreased among LPN calves. These data
      indicate that feeding a HPN to Jersey calves improved average daily gain and feed
      efficiency, but increased the incidence of high fecal scores during the first few
      weeks of life; however, the HPN Jersey calves may be more resistant to Salmonella
      Typhimurium after weaning. 

PMID- 25597968
TI  - Investigating the filled gel model in Cheddar cheese through use of Sephadex
      beads.
AB  - Cheese can be modeled as a filled gel whereby milkfat globules are dispersed in a
      casein gel network. We determined the filler effects using Sephadex beads (GE
      Healthcare Life Sciences, Pittsburgh, PA) as a model filler particle. Ideally,
      such a model could be used to test novel filler particles to replace milkfat in
      low-fat cheese. Low-filler (6% particles), reduced-filler (16%), and full-filler
      (33%) cheeses were produced using either Sephadex beads of varying sizes (20 to
      150 MUm diameter) or milkfat. Small- and large-strain rheological tests were run
      on each treatment at 8, 12, and 18 wk after cheese manufacturing. Differences in
      rheological properties were caused primarily by the main effects of filler volume
      and type (milkfat vs. Sephadex), whereas filler size had no obvious effect. All
      treatments showed a decrease in deformability and an increase in firmness as
      filler volume increased above 25%, although the beads exhibited a greater
      reinforcing effect and greater energy recovery than milkfat.

PMID- 25597969
TI  - Inactivation of Mycobacterium bovis ssp. caprae in high-temperature, short-term
      pasteurized pilot-plant milk.
AB  - Experiments to determine the efficacy of high temperature, short time (HTST)
      pasteurization of milk in terms of inactivation of pathogenic microorganisms were
      mainly performed between 1930 and 1960. Among the target organisms were
      Mycobacterium bovis and Mycobacterium tuberculosis. As a result, the Codex
      Alimentarius prescribes that HTST treatment of milk should lead to a significant
      reduction of pathogenic microorganisms during milk pasteurization. Due to the
      development of improved methods for the detection of survivors and of more
      advanced heating technology, verification of this requirement seemed to be
      necessary. To address recent outbreaks of tuberculosis in cattle caused by M.
      bovis ssp. caprae (M. caprae) in the southern regions of Germany, this organism
      was tested and compared with M. bovis ssp. bovis (M. bovis). Experiments were
      performed in a pilot plant for HTST pasteurization of milk with 3 strains of M.
      caprae and 1 strain of M. bovis. In preliminary trials at a fixed holding time of
      25 s, the temperature at which significant inactivation occurred was 62.5 degrees
      C for all strains. To determine D-values (decimal reduction times) for the
      inactivation kinetics, the strains were tested at 65, 62.5, and 60 degrees C at
      holding times of 16.5, 25, and 35 s. At 65 degrees C, the D-values of all strains
      ranged from 6.8 to 7.8 s, and at 62.5 degrees C, D-values ranged from 14.5 to
      18.1 s. Low inactivation was observed at 60 degrees C. When the low slope of the
      inactivation curve allowed calculation of a D-value, these ranged from 40.8 to
      129.9 s. In terms of log10 reductions, the highest values for all strains were
      4.1 to 4.9 log at 65 degrees C, with a holding time of 35 s. The tested strains
      of M. caprae and M. bovis showed similar low resistance to heat. Standard HTST
      treatment should result in a high reduction of these organisms and thus the
      requirements of the Codex Alimentarius for inactivation of pathogens by this
      process are far exceeded. 

PMID- 25597970
TI  - Heat-treated (in single aliquot or batch) colostrum outperforms non-heat-treated
      colostrum in terms of quality and transfer of immunoglobulin G in neonatal Jersey
      calves.
AB  - The objective of this randomized clinical trial was to describe the effect on
      colostrum characteristics and passive transfer of IgG in neonatal calves when
      using the Perfect Udder colostrum management system (single-aliquot treatment;
      Dairy Tech Inc., Greeley, CO) compared with a negative control (fresh
      refrigerated or fresh frozen colostrum) and a positive control (batch heat
      treated colostrum). First-milking Jersey colostrum was pooled to achieve 31
      unique batches with a minimum of 22.8 L per batch. The batch was then divided
      into 4 with 3.8 L allocated to each treatment group: (1) heat-treated in Perfect
      Udder bag at 60 degrees C for 60 min and then stored at -20 degrees C (PU); (2)
      heat-treated in a batch pasteurizer (Dairy Tech Inc.) at 60 degrees C for 60 min
      and then stored at -20 degrees C in Perfect Udder bag (DTB; positive control);
      (3) fresh frozen colostrum stored at -20 degrees C in Perfect Udder bag (FF;
      negative control); and (4) fresh refrigerated colostrum stored at 4 degrees C in
      Perfect Udder bag (FR; negative control). Colostrum from all treatments was
      sampled for analysis of IgG concentration and bacterial culture immediately after
      batch assembly, after processing, and before feeding. Newborn Jersey calves were
      randomly assigned to be fed 3.8 L of colostrum from 1 of the 4 treatment groups.
      A prefeeding, 0-h blood sample was collected, calves were fed by esophageal tube
      within 2 h of birth, and then a 24-h postfeeding blood sample was collected.
      Paired serum samples from 0- and 24-h blood samples were analyzed for IgG
      concentration (mg/mL) using radial immunodiffusion analysis. The overall mean IgG
      concentration in colostrum was 77.9 g/L and was not affected by treatment.
      Prefeeding total plate counts (log10 cfu/mL) were significantly different for all
      4 treatments and were lower for heat-treated colostrum (PU=4.23, DTB=3.63)
      compared with fresh colostrum (FF=5.68, FR=6.53). Total coliform counts (log10
      cfu/mL) were also significantly different for all 4 treatments and were lower for
      heat-treated colostrum (PU=0.45, DTB=1.08) compared with fresh colostrum
      (FF=3.82, FR=4.80). Mean 24-h serum IgG concentrations were significantly higher
      for calves in the PU (41.0 mg/mL) and DTB (40.6 mg/mL) groups compared with FF
      (35.1 mg/mL) and FR (35.5 mg/mL) groups. Mean apparent efficiency of absorption
      of IgG was significantly higher for the PU (37%) and DTB (37%) groups compared
      with the FF (32%) and FR (32%) groups. Calves fed heat-treated colostrum (PU or
      DTB) experienced significantly improved AEA and serum IgG concentrations.

PMID- 25597971
TI  - Novel approaches to genetic analysis of fertility traits in New Zealand dairy
      cattle.
AB  - The fertility of dairy cattle in New Zealand is well below industry targets, and
      the current New Zealand fertility breeding value (BV) could potentially be
      improved using additional information and traits. Data from 169 herds were
      analyzed to determine the benefits of using alternative phenotypic measures in
      the calculation of the fertility BV. The heritability of calving season day (CSD;
      calving season day as an integer day of the year) and the probability of an
      animal calving within 42 d of the planned start of calving (CR42) increased
      modestly (from 0.0206 to 0.0213 and 0.0087 to 0.0092, respectively) after
      accounting for the use of intravaginal progesterone-releasing devices for
      treatment of anestrous cows (anestrum treatment) and induced calvings. Incidence
      of either anestrum treatment or calving induction as a single binomial trait
      (AT/IND) had a heritability of 0.0223 and showed moderate genetic correlation
      with the probability of an animal being mated within 21 d of the planned start of
      mating (PM21; -0.4473), but much higher with CSD (0.8445). The use of pregnancy
      diagnosis data allowed fertility information that would otherwise be discarded to
      be included in analyses; when used to assign a prolonged CSD and a value of 0 for
      CR42 to animals that failed to calve, it increased the heritabilities of both of
      these traits (to 0.0278 and 0.0114, respectively). Because CSD was found to be
      more than twice as heritable as its binary counterpart, it shows potential to
      replace CR42 as the calving trait used in the fertility BV. Postpartum anestrous
      interval (PPAI), derived using incomplete premating estrous recording in some
      herds, had a heritability of 0.0813 and hence has potential as a trait to be
      included in genetic improvement programs but would require more rigorous
      recording of estrous during the premating period to be an effective trait. Based
      on selection index theory, the modifications made to current selection criteria
      using novel fertility traits increased the accuracy of prediction of fertility
      merit by more than 12%. Because of the increasing economic importance of
      fertility traits, and low heritabilities requiring large numbers of recorded
      daughters to get accurate fertility BV predictions on sires, data recorded on
      farm will become increasingly important in the genetic improvement of fertility.

PMID- 25597972
TI  - The effect of housing on calving behavior and calf vitality in Holstein and
      Jersey dairy cows.
AB  - The present study investigated how calving behavior and calf vitality in Holstein
      and Jersey dairy cows were affected by housing during the final 4 wk precalving.
      One hundred twenty-one cows (36 primiparous and 85 multiparous) were moved either
      to a group pen with deep straw bedding or into freestall housing 4 wk before the
      expected calving date. Individual straw-bedded maternity pens were placed
      adjacent to the straw-bedded group pens, and cows were moved to the maternity
      pens before calving. Cows that spent more than 12 h in the maternity pen before
      calving and calved unassisted were included in this study (39 multiparous cows
      and 15 primiparous cows). Dams were observed from 6 h before calving until 6 h
      after calving. The time from the onset of rhythmical abdominal contractions
      (defined as the onset of stage II labor), the time from a visible amniotic sac,
      and the time from visible calf feet until the birth of the calf were recorded.
      Furthermore, the cows' latency to stand up after birth was recorded. Calves were
      observed during the first 6 h after birth and the latency to first standing
      attempt, to first successful standing, to first suckle attempt, and to first
      successful suckling were recorded. Cows previously housed in straw pens expelled
      the calf faster once the calves' feet were visible compared with cows previously
      housed in freestalls. Multiparous cows stood sooner and licked their calf sooner
      after birth compared with primiparous cows. Jersey calves of cows previously
      housed in straw pens also stood up and suckled their dams sooner compared with
      Jersey calves of cows previously housed in freestalls. Holstein cows previously
      housed in straw pens tended to stand up sooner compared with Holstein cows
      previously housed in freestalls. These results suggest that a longer period of
      housing on deep-bedded straw compared with freestalls with mattresses before
      calving may facilitate the calving process, whereas the effect on calf vitality
      needs further investigation.

PMID- 25597973
TI  - Weight, height, and relative-reliability indicators as a management tool for
      reducing age at first breeding and calving of dairy heifers.
AB  - In Quebec first calving occurs on average at 27 mo, whereas the target is 23 to
      24.5 mo to maximize herd profitability. The aim of this study was to quantify
      current and future heifer growth using individual heifer random regressions and
      to generate indicators (such as heifer weight and height at 15 and 24 mo, average
      daily gain before and after 15 mo, age at which optimal weight for breeding is
      attained, i.e., 55% of mature weight, and reliability of the 15- and 24-mo weight
      predictions) that could be used as a practical on-farm tool. Dairy heifer weight
      estimated by heart girth circumference and height measured at the withers (from 0
      to 27 mo) were obtained from the Valacta database (DHI agency, Ste-Anne-de
      Bellevue, QC, Canada) from 1995 to 2012. Indicators were calculated based on the
      current situation of Holstein (HO), Ayrshire (AY), Jersey (JE), and Brown Swiss
      (BS) heifer growth in Quebec. Heifers with less than 2 records were excluded from
      the analysis. Mature weights were determined by weight at calving of cows from
      third or greater lactation for a given breed and were 710 kg for HO, 625 kg for
      AY, 470 kg for JE, and 670 kg for BS. Estimated weights at 15 and 24 mo were 425
      and 627, 334 and 482, 297 and 429, and 379 and 560 kg for HO, AY, JE, and BS,
      respectively, which are heavy enough for breeding and calving, except for AY.
      Relative reliabilities of the 15- and 24-mo weight predictions were on average 89
      and 60%, respectively, based on measurements up to 15 mo. For HO, AY, JE, and BS,
      wither heights at 15 and 24 mo were 134 and 143, 125 and 134, 122 and 131, and
      130 and 140 cm, respectively. Age at optimal breeding weight was 13.6, 15.5,
      12.6, and 14.5 mo for HO, AY, JE, and BS, respectively. These data suggest that
      it is realistic to expect a first calving at 24 mo for HO, JE, and BS. A growth
      delay was observed for AY; average daily gain was 655 and 538 g/d before and
      after 15 mo, respectively. The average daily gain before and after 15 mo was 848
      and 747 g/d for HO, 603 and 486 g/d for JE, and 775 and 662 g/d for BS,
      respectively. These indicators could be calculated for an individual heifer and
      on a herd-level basis and used on farm as a management tool for reducing age at
      first breeding and at first calving.

PMID- 25597974
TI  - Green cheese: partial life cycle assessment of greenhouse gas emissions and
      energy intensity of integrated dairy production and bioenergy systems.
AB  - The objective of this study was to evaluate the effect of integrating dairy and
      bioenergy systems on land use, net energy intensity (NEI), and greenhouse gas
      (GHG) emissions. A reference dairy farm system representative of Wisconsin was
      compared with a system that produces dairy and bioenergy products. This
      integrated system investigates the effects at the farm level when the cow diet
      and manure management practices are varied. The diets evaluated were supplemented
      with varying amounts of dry distillers grains with solubles and soybean meal and
      were balanced with different types of forages. The manure-management scenarios
      included manure land application, which is the most common manure disposal method
      in Wisconsin, and manure anaerobic digestion (AD) to produce biogas. A partial
      life cycle assessment from cradle to farm gate was conducted, where the system
      boundaries were expanded to include the production of biofuels in the analysis
      and the environmental burdens between milk and bioenergy products were
      partitioned by system expansion. Milk was considered the primary product and the
      functional unit, with ethanol, biodiesel, and biogas considered co-products. The
      production of the co-products was scaled according to milk production to meet the
      dietary requirements of each selected dairy ration. Results indicated that land
      use was 1.6 m2, NEI was 3.86 MJ, and GHG emissions were 1.02 kg of CO2
      equivalents per kilogram of fat- and protein-corrected milk (FPCM) for the
      reference system. Within the integrated dairy and bioenergy system, diet
      scenarios that maximize dry distillers grains with solubles and implement AD had
      the largest reduction of GHG emissions and NEI, but the greatest increase in land
      use compared with the reference system. Average land use ranged from 1.68 to 2.01
      m2/kg of FPCM; NEI ranged from -5.62 to -0.73 MJ/kg of FPCM; and GHG emissions
      ranged from 0.63 to 0.77 kg of CO2-equivalents/kg of FPCM. The AD contributed 65%
      of the NEI and 77% of the GHG emission reductions.

PMID- 25597975
TI  - Effect of dissolved oxygen on redox potential and milk acidification by lactic
      acid bacteria isolated from a DL-starter culture.
AB  - Milk acidification by DL-starter cultures [cultures containing Lactococcus lactis
      diacetylactis (D) and Leuconostoc (L) species] depends on the oxidation-reduction
      (redox) potential in milk; however, the mechanisms behind this effect are not
      completely clear. The objective of this study was to investigate the effect of
      dissolved oxygen on acidification kinetics and redox potential during milk
      fermentation by lactic acid bacteria (LAB). Fermentations were conducted by
      single strains isolated from mixed DL-starter culture, including Lactococcus
      lactis ssp. lactis, Lactococcus lactis ssp. cremoris, and Leuconostoc
      mesenteroides ssp. cremoris, by the DL-starter culture, and by the type strains.
      High and low levels of oxygen were produced by flushing milk with oxygen or
      nitrogen, respectively. The kinetics of milk acidification was characterized by
      the maximum rate and time of acidification (Vamax and Tamax), the maximum rate
      and time of reduction (Vrmax and Trmax), the minimum redox potential (Eh7 final),
      and time of reaching Eh7 final (Trfinal). Variations in kinetic parameters were
      observed at both the species and strain levels. Two of the Lc. lactis ssp. lactis
      strains were not able to lower redox potential to negative values. Kinetic
      parameters of the DL-starter culture were comparable with the best acidifying and
      reducing strains, indicating their additive effects. Acidification curves were
      mostly diauxic at all oxygen levels, displaying 2 maxima of acidification rate:
      before (aerobic maximum) and after (anaerobic maximum) oxygen depletion. The
      redox potential decreased concurrently with oxygen consumption and continued to
      decrease at slower rate until reaching the final values, indicating involvement
      of both oxygen and microbiological activity in the redox state of milk. Oxygen
      flushing had a negative effect on reduction and acidification capacity of tested
      LAB. Reduction was significantly delayed at high initial oxygen, exhibiting
      longer Trmax, Trfinal, or both. Concurrently, anaerobic acidification rate
      maximum Vamax was decreased and Tamax was extended. Fermentation kinetics in
      nitrogen-flushed milk was not statistically different from that in untreated milk
      except for Lc. lactis ssp. lactis CHCC D2, which showed faster reduction time
      after nitrogen flushing. This study clarifies the relationship between the redox
      state in milk and acidification kinetics of the predominant subspecies in DL
      starter cultures. This knowledge is important for dairies to ensure optimized,
      fast, and controlled milk fermentations, leading to greater standardization of
      dairy products.

PMID- 25597977
TI  - Off-site rearing of heifers reduces the risk of Mycobacterium avium ssp.
      paratuberculosis ELISA seroconversion and fecal shedding in a California dairy
      herd.
AB  - The objective of this cohort study was to evaluate whether rearing dairy heifers
      at different premises than the dairy of origin (off-site) reduced the risk of
      Mycobacterium avium ssp. paratuberculosis (MAP) infection more effectively than
      rearing on the dairy of origin (on-site). From 2003 to 2005, 3 cohorts of Jersey
      heifers were born on a single California dairy, with heifers in the first cohort
      raised on-site until first calving (n=797); heifers in the second cohort raised
      on-site until approximately 5 mo of age and off-site until about 1 to 2 mo
      precalving (n=791); and heifers in the third cohort raised off-site from d 1
      until about 1 to 2 mo before first calving (n=797). Cohorts were sequentially
      enrolled, and heifers were followed until death, culling, or up to 6 yr of age.
      Heifers were tested annually for MAP infection by serum ELISA and bacterial
      culture of feces, from lactation 1 until they were 6 yr old, and all mortality
      and culling events were recorded. Compared with cohort 1, cohort 3 had lower
      hazards of seroconverting and shedding of MAP in feces, approximately 70 and 38%,
      respectively. Cohort 2 was not significantly different from cohort 1 for the same
      outcomes. Mortality hazards were only significantly different between cohorts
      before first calving, with calves raised completely off-site at lower risk than
      the remaining 2 cohorts. Additionally, the hazards for culling in cohorts 2 and 3
      were only significantly different from cohort 1 after the first calving. To our
      knowledge, the current study is the first cohort study to evaluate the
      association between off-site heifer rearing and risk of MAP infection, mortality,
      and culling. Rearing heifer calves off-site, away from infected adult dairy cows,
      may have allowed for reduced exposure to MAP in the environment of the calves
      and, hence, served as a control strategy for Johne's disease.

PMID- 25597976
TI  - Characteristics of enterotoxin distribution, hemolysis, lecithinase, and starch
      hydrolysis of Bacillus cereus isolated from infant formulas and ready-to-eat
      foods.
AB  - Bacillus cereus is a ubiquitous environmental microbe implicated as a main cause
      of food poisoning with various symptoms, depending on the strain type and the
      isolation source. In this study, the potential virulence factors and biochemical
      properties of B. cereus isolated from infant formulas and ready-to-eat (RTE)
      foods were analyzed and compared. A total of 347 B. cereus strains were isolated
      and identified from 687 infant food formulas and RTE food samples. All the
      isolates had one or more enterotoxin genes, and one-half of the strains had all 3
      enterotoxin genes (hbl, nhe, and cytK) that are involved in food poisoning in
      humans. Here, all the 3 genes were detected in 50% of the B. cereus isolates from
      RTE foods and only 14% of the isolates were identified from infant formulas. The
      latter harbored low cytK and bceT, and very low hbl genes. Most B. cereus
      isolates possessed the hemolysis gene, but not the ces gene. The infant formula
      isolates showed stronger hemolysis activity than the other isolates. In addition,
      26% of the total isolates showed low lecithinase activities and 10% showed high
      lecithinase activities. A greater number of isolates from the infant formula
      showed high lecithinase activity than those from the RTE foods. Approximately 83%
      of the isolates were positive and 17% were negative for starch hydrolysis. Over
      90% of the RTE food isolates and only 35% of the infant formula isolates were
      positive for starch hydrolysis. However, all the strains possessed nhe, but their
      harboring patterns of hbl and cytK were significantly different. Most starch
      hydrolyzing strains possessed hbl, but only 23% nonstarch-hydrolyzing isolates
      possessed this gene. Moreover, very low nonstarch hydrolyzing strains harbored
      cytK. Most nonstarch-hydrolyzing isolates showed high lecithinase and strong
      hemolysis activities, and very low hbl and cytK harboring. In summary, most
      infant formula isolates showed stronger hemolysis and higher lecithinase
      activities with lower frequency of harboring hbl and cytK and lower starch
      hydrolysis compared with RTE food isolates. 

PMID- 25597978
TI  - Effect of commercial grape extracts on the cheese-making properties of milk.
AB  - Grape extracts can be added to milk to produce cheese with a high concentration
      of polyphenols. Four commercial extracts from whole grape, grape seed, and grape
      skin (2 extracts) were characterized and added to milk at concentrations of 0,
      0.1, 0.2, and 0.3% (wt/vol). The effect of grape extracts on the kinetics of milk
      clotting, milk gel texture, and syneresis were determined, and model cheeses were
      produced. Whole grape and grape seed extracts contained a similar concentration
      of polyphenolic compounds and about twice the amount found in grape skin
      extracts. Radical scavenging activity was directly proportional to the phenolic
      compounds content. When added to milk, grape extracts increased rennet-induced
      clotting time and decreased the clotting rate. Although differences were observed
      between the extracts, the concentration added to milk was the main factor
      influencing clotting properties. With increasing concentrations of grape
      extracts, milk gels showed increased brittleness and reduced firmness. In
      addition, syneresis of milk gels decreased with increasing concentrations of
      grape extracts, which resulted in cheeses with a higher moisture content. The
      presence of grape extracts in milk slightly increased protein recovery in cheese
      but had no effect on fat recovery. With whole grape or grape seed extracts added
      to milk at 0.1% (wt/vol), the recovery coefficient for polyphenols was about
      0.63, and decreased with increasing extract concentration in milk. Better
      polyphenol recovery was observed for grape seed extracts (0.87), with no
      concentration effect. Commercial extracts from whole grape, grape seed, or grape
      skin can be added to milk in the 0.1 to 0.3% (wt/vol) concentration range to
      produce cheese with potential health benefits, without a negative effect on
      cheese yield. 

PMID- 25597979
TI  - An original cause of pulmonary hypertension.

PMID- 25597980
TI  - Documented but non-induced supraventricular tachycardia and vice versa.

PMID- 25597981
TI  - Defibrillator patients should not be denied a peaceful death.
AB  - BACKGROUND: Implantable defibrillators (ICDs) prevent sudden cardiac death. With
      declining health, ICD therapy may prolong death and expose the patient to
      unnecessary pain and anxiety. Few studies have addressed end of life care in ICD
      patients. The objective of this study was to investigate end of life in ICD
      patients, with respect to location of death; duration between do-not-resuscitate
      (DNR)-orders and deactivation of ICD therapy or DNR and time of death. METHODS
      AND RESULTS: A descriptive analysis of 65 deceased ICD patients, all whom had a
      written DNR-order before death, is presented. The majority (86%) was treated in
      hospitals, mainly (63%) university hospitals, and many (33%) in cardiology wards.
      Despite DNR-order, ICD shock therapy was active in 51% of all patients. In those
      with therapy deactivated at death, therapy deactivation was carried out two days
      or more after DNR-order in more than a third (38%). The time from DNR decision to
      death in patients with therapy active had a median of four days (IQR 1-38).
      During the last 24h of life, 24% of the patients experienced shock treatment.
      CONCLUSIONS: The majority of ICD patients with a DNR-order were treated in
      university hospitals. More than half still had shock treatment active at time of
      death with a median of four days or more between DNR decision and death. Patients
      with therapy deactivated, two days or more elapsed in more than a third from DNR
      decision to deactivation of therapy, exposing patients to a high risk of painful
      shocks before death.

PMID- 25597982
TI  - Prostate atypia: does repeat biopsy detect clinically significant prostate
      cancer?
AB  - BACKGROUND: While the treatment pathway in response to benign or malignant
      prostate biopsies is well established, there is uncertainty regarding the risk of
      subsequently diagnosing prostate cancer when an initial diagnosis of prostate
      atypia is made. As such, we investigated the likelihood of a repeat biopsy
      diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed
      prostate atypia. METHODS: We reviewed our prospectively maintained prostate
      biopsy database to identify patients who underwent a repeat prostate biopsy
      within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis
      between November 1987 and March 2011. Patients with a history of PCa were
      excluded. Chart review identified patients who underwent radical prostatectomy
      (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients
      were divided into two subgroups based on their date of service. RESULTS: Ten
      thousand seven hundred and twenty patients underwent 13,595 biopsies during
      November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP
      on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy
      within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19
      (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa.
      Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy
      were determined to have clinically significant tumors. 37 (36.3%) proceeded to
      RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In
      patients who underwent surgery, Gleason grade on final pathology was upgraded in
      11 (35.5%), and downgraded 1 (3.2%) patient. CONCLUSIONS: ASAP on initial biopsy
      was associated with a significant risk of PCa on repeat biopsy in patients who
      subsequently underwent definitive local therapy. Patients with ASAP should be
      counseled on the probability of harboring both clinically significant and
      insignificant prostate cancer.

PMID- 25597983
TI  - In situ TEM study of the Li-Au reaction in an electrochemical liquid cell.
AB  - We study the lithiation of a Au electrode in an electrochemical liquid cell using
      transmission electron microscopy (TEM). The commercial liquid electrolyte for
      lithium ion batteries (1 M lithium hexafluorophosphate LiPF6 dissolved in 1 : 1
      (v/v) ethylene carbonate (EC) and diethyl carbonate (DEC)) was used. Three
      distinct types of morphology change during the reaction, including gradual
      dissolution, explosive reaction and local expansion/shrinkage, are observed. It
      is expected that significant stress is generated from lattice expansion during
      lithium-gold alloy formation. There is vigorous bubble formation from electrolyte
      decomposition, likely due to the catalytic effect of Au, while the bubble
      generation is less severe with titanium electrodes. There is an increase of
      current in response to electron beam irradiation, and electron beam effects on
      the observed electrochemical reaction are discussed. 

PMID- 25597984
TI  - Highly enantioselective catalytic 1,3-dipolar cycloadditions of alpha-alkyl
      diazoacetates: efficient synthesis of functionalized 2-pyrazolines.
AB  - Highly enantioselective 1,3-dipolar cycloaddition reactions of alpha-substituted
      diazoacetates are accomplished by catalysis of the chiral oxazaborolidinium ion.
      Functionalized 2-pyrazolines are synthesized in high to excellent enantiomeric
      ratios (up to >99 : 1). The synthetic utility of 2-pyrazoline was expanded via
      preparation of 2,4-diamino ester compounds bearing a chiral quaternary carbon
      center. 

PMID- 25597986
TI  - The endothelial glycocalyx: the great luminal barrier.

PMID- 25597985
TI  - Cell-free expression, purification, and ligand-binding analysis of Drosophila
      melanogaster olfactory receptors DmOR67a, DmOR85b and DmORCO.
AB  - Insects transmit numerous devastating diseases, including malaria, dengue fever,
      and sleeping sickness. Olfactory cues guide insects to their hosts, and are thus
      responsible for disease transmission. Understanding the molecular basis of insect
      olfaction could facilitate the development of interventions. The first step is to
      heterologously overexpress and purify insect olfactory receptors (ORs). This is
      challenging, as ORs are membrane proteins. Here, we show that insect ORs and
      their co-receptor can be expressed in an E. coli cell-free system. After
      immunoaffinity chromatography, the ORs are ~95% pure, and up to 1 mg/10 ml
      reaction is obtained. Circular dichroism together with microscale thermophoresis
      indicate that each receptor is properly folded, and can bind its respective
      ligand. This is the first time insect ORs have been expressed in an E. coli
      system. The methods described here could facilitate future structure-function
      studies, which may aid in developments to alleviate the suffering of millions
      caused by insect-transmitted diseases.

PMID- 25597987
TI  - On the quest for stress-free surgical operations.

PMID- 25597988
TI  - In-hospital C-reactive protein predicts outcome after aneurysmal subarachnoid
      haemorrhage treated by endovascular coiling.
AB  - BACKGROUND: This study aimed to examine prospectively whether the inflammatory
      marker C-reactive protein (CRP) increases in patients with aneurysmal
      subarachnoid haemorrhage (aSAH) treated by endovascular coiling and investigate
      whether CRP could be used as prognostic factor for long-term neurological
      outcome. METHODS: This single-hospital study comprised 98 consecutive patients
      with confirmed aSAH treated by endovascular coiling. Admission status was
      classified according to the World Federation of Neurosurgical Societies (WFNS)
      Scale and initial cerebral computed tomography according to Fisher scale. CRP was
      analysed on days 0, 1, 2, 3, 4, 6 and 8 after the initial bleed. A neurological
      follow up was performed 1 year later according to the Extended Glasgow Outcome
      Scale (GOSE) for overall outcome and National Institute of Health Stroke Scale
      (NIHSS) for focal deficit. RESULTS: CRP values increased from normal to peak at
      53 mg/l at day 3-4 and then declined, without normalising, at day 8. Patients
      with a higher increase in CRP had a poorer neurological outcome after 1 year. CRP
      during the first week had a stronger correlation to outcome (r = 0.417) and NIHSS
      (r = 0.449) than initial clinical status (WFNS; r = 0.280 and 0.274) and
      radiology (Fisher scale; r = 0.137 and 0.158). CRP increase indicated a risk of
      poor outcome (GOSE) (P < 0.001) and permanent loss of neurological function
      (NIHSS) (P < 0.001). Logistic regression analysis suggested that elevated CRP
      already on day 2 is an independent prognostic marker for outcome. CONCLUSION:
      Early CRP values can perhaps be used as a prognostic factor for long-term
      neurological outcome prediction after endovascular treatment of aSAH.

PMID- 25597991
TI  - Pd(0)-catalyzed chemoselective construction of spirocarbocycles via an alkyne
      insertion/beta-naphthol dearomatization cascade.
AB  - A microwave-assisted Pd(0)-catalyzed alkyne migratory insertion/beta-naphthol
      dearomatization cascade process has been accomplished to access a variety of
      spirocyclic compounds bearing all-carbon quaternary stereogenic centers in high
      yields with excellent chemoselectivities. 

PMID- 25597992
TI  - The peculiar behavior of Picha in the formation of metallacrown complexes with
      Cu(II), Ni(II) and Zn(II) in aqueous solution.
AB  - The thermodynamic stability of the metallacrown complexes formed by
      picolinehydroxamic acid (Picha) with Cu(ii), Ni(ii) and Zn(ii) in aqueous
      solution has been determined by potentiometry, and the speciation models were
      validated by ESI-MS and UV-visible spectrophotometry. Cu(ii) and Zn(ii) form 12
      MC-4 species as the unique metallacrowns present in the solution. While for
      Cu(ii) the 12-MC-4 is slightly less stable than that obtained with
      alaninehydroxamic acid (Alaha), the opposite was found for Zn(ii). Moreover, with
      Cu(ii) unprecedented 15-MC-5 and 18-MC-6 species were identified under ESI-MS
      conditions. Picha with Ni(ii) forms, in contrast, a 15-MC-5 complex as a unique
      metallacrown species. Structural studies of the framework of the 12-MC-4
      complexes by ab initio methods were also carried out. The results of our
      investigations allowed us to rationalize not only the different behaviour of
      Picha in the formation of metallacrowns with the three metal ions, but also the
      reasons which underpin the strategies for stabilization of these species reported
      in the literature using ancillary ligands such as pyridine. 

PMID- 25597993
TI  - Evaluation of the formation of a junctional DNA nanostructure through annealing
      curve analysis.
AB  - During the self-assembly of different numbers of oligonucleotides comprising
      junctional DNA nanostructures, a change in environmental variables (e.g.,
      temperature or salt concentration) has a substantial influence on the final
      products. Further, distinctive annealing temperatures of oligonucleotides are
      observed depending on the state of hybridization. Here, we present an evaluation
      of the annealing characteristics of oligonucleotides for the formation of a
      simple junctional DNA nanostructure using an annealing curve analysis. This
      method may be useful for analyzing the formation of complex junctional DNA
      nanostructures. 

PMID- 25597990
TI  - Novel variation and de novo mutation rates in population-wide de novo assembled
      Danish trios.
AB  - Building a population-specific catalogue of single nucleotide variants (SNVs),
      indels and structural variants (SVs) with frequencies, termed a national pan
      genome, is critical for further advancing clinical and public health genetics in
      large cohorts. Here we report a Danish pan-genome obtained from sequencing 10
      trios to high depth (50 * ). We report 536k novel SNVs and 283k novel short
      indels from mapping approaches and develop a population-wide de novo assembly
      approach to identify 132k novel indels larger than 10 nucleotides with low false
      discovery rates. We identify a higher proportion of indels and SVs than previous
      efforts showing the merits of high coverage and de novo assembly approaches. In
      addition, we use trio information to identify de novo mutations and use a
      probabilistic method to provide direct estimates of 1.27e-8 and 1.5e-9 per
      nucleotide per generation for SNVs and indels, respectively. 

PMID- 25597994
TI  - Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7
      hypothalamic neurons.
AB  - Insulin signaling in the hypothalamus plays an important role in food intake and
      glucose homeostasis. Hypothalamic neuronal functions are modulated by glial
      cells; these form an extensive network connecting the neurons and cerebral
      vasculature, known as the neurovascular unit (NVU). Brain pericytes are
      periendothelial accessory structures of the blood-brain barrier and integral
      members of the NVU. However, the interaction between pericytes and neurons is
      largely unexplored. Here, we investigate whether brain pericytes could affect
      hypothalamic neuronal insulin signaling. Our immunohistochemical observations
      demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting
      immunoreactivity of platelet-derived growth factor receptor beta (a pericyte
      marker), and laminin, a basal lamina marker. We then exposed a murine
      hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from
      primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but
      not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the
      insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration
      dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation
      of insulin receptor beta without changing its expression or localization in
      cytosolic or plasma membrane fractions. These results suggest that pericytes,
      rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by
      releasing soluble factors under physiological conditions in the NVU. 

PMID- 25597995
TI  - Bcl6 promotes osteoblastogenesis through Stat1 inhibition.
AB  - Bone mass is tightly controlled by a balance between osteoclast and osteoblast
      activities. Although these cell types mature via different pathways, some factors
      reportedly regulate differentiation of both. Here, in a search for factors
      governing osteoblastogenesis but also expressed in osteoclasts to control both
      cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of
      those factors and show that it promotes osteoblast differentiation. Bcl6 was
      previously shown to negatively regulate osteoclastogenesis. We report that lack
      of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in
      vitro and in defects in secondary ossification center formation in vivo. Signal
      transducer and activator of transcription 1 (Stat1) reportedly attenuates
      osteoblast differentiation by inhibiting nuclear translocation of runt-related
      transcription factor 2 (Runx2), which is essential for osteoblast
      differentiation. We found that lack of Bcl6 resulted in significant elevation of
      Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a
      direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking
      both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and
      osteoblastic parameters as well as partial rescue of secondary ossification
      center formation compared with Bcl6-deficient mice in vivo. Altered
      osteoblastogenesis in Bcl6-deficient cells was also restored in DKO in vitro.
      Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and
      osteoclast inhibition.

PMID- 25597996
TI  - Asparagine 326 in the extremely C-terminal region of XRCC4 is essential for the
      cell survival after irradiation.
AB  - XRCC4 is one of the crucial proteins in the repair of DNA double-strand break
      (DSB) through non-homologous end-joining (NHEJ). As XRCC4 consists of 336 amino
      acids, N-terminal 200 amino acids include domains for dimerization and for
      association with DNA ligase IV and XLF and shown to be essential for XRCC4
      function in DSB repair and V(D)J recombination. On the other hand, the role of
      the remaining C-terminal region of XRCC4 is not well understood. In the present
      study, we noticed that a stretch of ~20 amino acids located at the extreme C
      terminus of XRCC4 is highly conserved among vertebrate species. To explore its
      possible importance, series of mutants in this region were constructed and
      assessed for the functionality in terms of ability to rescue radiosensitivity of
      M10 cells lacking XRCC4. Among 13 mutants, M10 transfectant with N326L mutant
      (M10-XRCC4(N326L)) showed elevated radiosensitivity. N326L protein showed
      defective nuclear localization. N326L sequence matched the consensus sequence of
      nuclear export signal. Leptomycin B treatment accumulated XRCC4(N326L) in the
      nucleus but only partially rescued radiosensitivity of M10-XRCC4(N326L). These
      results collectively indicated that the functional defects of XRCC4(N326L) might
      be partially, but not solely, due to its exclusion from nucleus by synthetic
      nuclear export signal. Further mutation of XRCC4 Asn326 to other amino acids,
      i.e., alanine, aspartic acid or glutamine did not affect the nuclear localization
      but still exhibited radiosensitivity. The present results indicated the
      importance of the extremely C-terminal region of XRCC4 and, especially, Asn326
      therein.

PMID- 25597997
TI  - Efficient generation of T2*-weighted contrast by interslice echo-shifting for
      human functional and anatomical imaging at 9.4 Tesla.
AB  - PURPOSE: Standard gradient-echo sequences are often prohibitively slow for T2*
      weighted imaging as long echo times prolong the repetition time of the sequence.
      Echo-shifting offers a way out of this dilemma by allowing an echo time that
      exceeds the repetition time. The purpose of this work is to present a gradient
      echo sequence that is optimized for multislice T2*-weighted imaging applications
      by combining echo-shifting with an interleaved slice excitation order. THEORY AND
      METHODS: This combined approach offers two major advantages: First, it combines
      the advantages of both concepts, that is, echo time and pulse repetition time can
      be significantly increased without affecting scan time. Second, there is no echo
      shifting related signal loss associated with this concept as only a single
      radiofrequency pulse is applied per pulse repetition time and slice. RESULTS: A
      9.4 Tesla high-resolution T2*-weighted anatomical brain scan of the proposed
      sequence is compared to a standard gradient-echo. Furthermore, results from 9.4
      Tesla blood oxygen level dependent functional magnetic resonance imaging
      experiments with an in-plane resolution of 0.8 * 0.8 mm(2) are presented.
      CONCLUSION: The proposed sequence allows for efficient generation of T2*-weighted
      contrast by combining echo-shifting with an interleaved slice excitation order.

PMID- 25597998
TI  - Auxiliary iron-sulfur cofactors in radical SAM enzymes.
AB  - A vast number of enzymes are now known to belong to a superfamily known as
      radical SAM, which all contain a [4Fe-4S] cluster ligated by three cysteine
      residues. The remaining, unligated, iron ion of the cluster binds in contact with
      the alpha-amino and alpha-carboxylate groups of S-adenosyl-l-methionine (SAM).
      This binding mode facilitates inner-sphere electron transfer from the reduced
      form of the cluster into the sulfur atom of SAM, resulting in a reductive
      cleavage of SAM to methionine and a 5'-deoxyadenosyl radical. The 5'
      deoxyadenosyl radical then abstracts a target substrate hydrogen atom, initiating
      a wide variety of radical-based transformations. A subset of radical SAM enzymes
      contains one or more additional iron-sulfur clusters that are required for the
      reactions they catalyze. However, outside of a subset of sulfur insertion
      reactions, very little is known about the roles of these additional clusters.
      This review will highlight the most recent advances in the identification and
      characterization of radical SAM enzymes that harbor auxiliary iron-sulfur
      clusters. This article is part of a Special Issue entitled: Fe/S proteins:
      Analysis, structure, function, biogenesis and diseases. 

PMID- 25597999
TI  - Functional consequences of the oligomeric assembly of proteorhodopsin.
AB  - The plasma membrane is the crucial interface between the cell and its exterior,
      packed with embedded proteins experiencing simultaneous protein-protein and
      protein-membrane interactions. A prominent example of cell membrane complexity is
      the assembly of transmembrane proteins into oligomeric structures, with potential
      functional consequences that are not well understood. From the study of
      proteorhodopsin (PR), a prototypical seven-transmembrane light-driven bacterial
      proton pump, we find evidence that the inter-protein interaction modulated by
      self-association yields functional changes observable from the protein interior.
      We also demonstrate that the oligomer is likely a physiologically relevant form
      of PR, as crosslinking of recombinantly expressed PR reveals an oligomeric
      population within the Escherichia coli membrane (putatively hexameric). Upon
      chromatographic isolation of oligomeric and monomeric PR in surfactant micelles,
      the oligomer exhibits distinctly different optical absorption properties from
      monomeric PR, as reflected in a prominent decrease in the pKa of the primary
      proton acceptor residue (D97) and slowing of the light-driven conformational
      change. These functional effects are predominantly determined by specific PR-PR
      contacts over nonspecific surfactant interactions. Interestingly, varying the
      surfactant type alters the population of oligomeric states and the proximity of
      proteins within an oligomer, as determined by sparse electron paramagnetic
      resonance distance measurements. Nevertheless, the dynamic surfactant environment
      retains the key function-tuning property exerted by oligomeric contacts. A
      potentially general design principle for transmembrane protein function emerges
      from this work, one that hinges on specific oligomeric contacts that can be
      modulated by protein expression or membrane composition. 

PMID- 25598000
TI  - Tafazzins from Drosophila and mammalian cells assemble in large protein complexes
      with a short half-life.
AB  - Tafazzin is a transacylase that affects cardiolipin fatty acid composition and
      mitochondrial function. Mutations in human tafazzin cause Barth syndrome yet the
      enzyme has mostly been characterized in yeast. To study tafazzin in higher
      organisms, we isolated mitochondria from Drosophila and mammalian cell cultures.
      Our data indicate that tafazzin binds to multiple protein complexes in these
      organisms, and that the interactions of tafazzin lack strong specificity. Very
      large tafazzin complexes could only be detected in the presence of cardiolipin,
      but smaller complexes remained intact even upon treatment with phospholipase A2.
      In mammalian cells, tafazzin had a half-life of only 3-6h, which was much shorter
      than the half-life of other mitochondrial proteins. The data suggest that
      tafazzin is a transient resident of multiple protein complexes. 

PMID- 25598001
TI  - The Northwick Park Therapy Dependency Assessment scale: a psychometric analysis
      from a large multicentre neurorehabilitation dataset.
AB  - PURPOSE: To assess the internal reliability, construct and concurrent validity
      and responsiveness of the Northwick Park Therapy Dependency Assessment (NPTDA)
      scale. METHOD: A cohort of 2505 neurorehabilitation patients submitted to the UK
      Rehabilitation Outcomes Collaborative database. Cronbach's coefficient-alpha was
      used to assess internal reliability and factor analysis (FA) to assess construct
      validity. We compared NPTDA scores at admission and discharge to determine
      responsiveness. RESULTS: Coefficient-alpha for the whole scale was 0.74. The
      exploratory FA resulted in a four-factor model (Physical, Psychosocial, Discharge
      planning and Activities) that accounted for 43% of variance. This model was
      further supported by the confirmatory FA. The final model had a good fit: root
      mean-square error of approximation of 0.069, comparative fit index/Tucker-Lewis
      index of 0.739/0.701 and the goodness of fit index of 0.909. The NPTDA scores at
      admission and discharge were significantly different for each of the factors.
      Expected correlations were seen between the admission scores for the NPTDA, the
      Rehabilitation Complexity Scale (r = 0.30, p < 0.01) and the Functional
      Independence Measure (r = -0.25, p < 0.01). CONCLUSIONS: The scale demonstrated
      acceptable internal reliability and good construct and concurrent validity. NPTDA
      may be used to describe and quantify changes in therapy inputs in the course of a
      rehabilitation programme. Implications for Rehabilitation The Northwick Park
      Therapy Dependency Assessment (NPTDA) is designed as a measure therapy
      intervention, which reflects both quantitative and qualitative aspects of the
      inputs provided (including staff time and the different types of intervention)
      during inpatient rehabilitation. The scale demonstrated acceptable internal
      reliability and good construct and concurrent validity. NPTDA is responsive to
      change in the therapy inputs provided during neurorehabilitation between
      admission and discharge.

PMID- 25598003
TI  - Redox activity of surface oxygen anions in oxygen-deficient perovskite oxides
      during electrochemical reactions.
AB  - Surface redox-active centres in transition-metal oxides play a key role in
      determining the efficacy of electrocatalysts. The extreme sensitivity of surface
      redox states to temperatures, to gas pressures and to electrochemical reaction
      conditions renders them difficult to investigate by conventional surface-science
      techniques. Here we report the direct observation of surface redox processes by
      surface-sensitive, operando X-ray absorption spectroscopy using thin-film iron
      and cobalt perovskite oxides as model electrodes for elevated-temperature oxygen
      incorporation and evolution reactions. In contrast to the conventional view that
      the transition metal cations are the dominant redox-active centres, we find that
      the oxygen anions near the surface are a significant redox partner to molecular
      oxygen due to the strong hybridization between oxygen 2p and transition metal 3d
      electronic states. We propose that a narrow electronic state of significant
      oxygen 2p character near the Fermi level exchanges electrons with the oxygen
      adsorbates. This result highlights the importance of surface anion-redox
      chemistry in oxygen-deficient transition-metal oxides. 

PMID- 25598005
TI  - Narrative in nursing practice, education and research.

PMID- 25598002
TI  - Proteomic profiling of patient-derived glioblastoma xenografts identifies a
      subset with activated EGFR: implications for drug development.
AB  - The development of drugs to inhibit glioblastoma (GBM) growth requires reliable
      pre-clinical models. To date, proteomic level validation of widely used patient
      derived glioblastoma xenografts (PDGX) has not been performed. In the present
      study, we characterized 20 PDGX models according to subtype classification based
      on The Cancer Genome Atlas criteria, TP53, PTEN, IDH 1/2, and TERT promoter
      genetic analysis, EGFR amplification status, and examined their proteomic
      profiles against those of their parent tumors. The 20 PDGXs belonged to three of
      four The Cancer Genome Atlas subtypes: eight classical, eight mesenchymal, and
      four proneural; none neural. Amplification of EGFR gene was observed in 9 of 20
      xenografts, and of these, 3 harbored the EGFRvIII mutation. We then performed
      proteomic profiling of PDGX, analyzing expression/activity of several proteins
      including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between
      PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20
      PDGX into high (n = 5) and low (n = 15) groups identified a panel of proteins
      associated with high EGFR activity. Thus, PDGX with high EGFR activity represent
      an excellent pre-clinical model to develop therapies for a subset of GBM patients
      whose tumors are characterized by high EGFR activity. Further, the proteins found
      to be associated with high EGFR activity can be monitored to assess the
      effectiveness of targeting EGFR. The development of drugs to inhibit glioblastoma
      (GBM) growth requires reliable pre-clinical models. We validated proteomic
      profiles using patient-derived glioblastoma xenografts (PDGX), characterizing 20
      PDGX models according to subtype classification based on The Cancer Genome Atlas
      (TCGA) criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR
      amplification status, and examined their proteomic profiles against those of
      their parent tumors. Proteins found to be associated with high EGFR activity
      represent potential biomarkers for GBM monitoring.

PMID- 25598006
TI  - The implications of Kristeva's notion of the abject in understanding the
      significance of therapeutic knowledge and practice in mental health nursing.
AB  - ACCESSIBLE SUMMARY: Mental health nursing knowledge is largely excluded in
      certain key clinical guideline groups despite nursing practice being so important
      to service users. This exclusion may be because mental health nurses work close
      to what cannot be spoken of easily, or at all--the abject. Good mental health
      nursing practice depends on the individual person of the mental health nurse
      rather than any knowledge frameworks. Education should focus on relational
      aspects of practice to develop this and to define the core identity of mental
      health nursing as a therapy. This paper discusses therapeutic knowledge and
      practice in mental health nursing through Kristeva's notion of the abject as that
      which is the other side of language, closely linked to the feminine space of the
      chora. The chora is a provisional, stable space, associated with the mother's
      body, where the first possibility of signification can take place. Mental health
      nursing is a therapeutic practice that draws on knowledge that is practical,
      tacit, empirical, embodied and intuitive, as well as knowledge that is regarded
      here as beyond the tacit; the latter indicating an encounter with the abject.
      Mental health nursing as a practice potentially places an extraordinary ethical
      onus on the individual nurse in his/her relations with patients and indicates
      that it is the person of the nurse who is therapeutic rather than any knowledge
      framework, with major implications for education and professional identity. The
      presence of mental health nursing practice at the heart of the mental health care
      system, while effectively being ignored as a treatment by the National Institute
      for Health and Care Excellence, embodies a critique of the currently dominant
      evidence-based paradigm.

PMID- 25598007
TI  - Linearly constrained minimum variance spatial filtering for localization of
      conductivity changes in electrical impedance tomography.
AB  - We localize dynamic electrical conductivity changes and reconstruct their time
      evolution introducing the spatial filtering technique to electrical impedance
      tomography (EIT). More precisely, we use the unit-noise-gain constrained
      variation of the distortionless-response linearly constrained minimum variance
      spatial filter. We address the effects of interference and the use of zero gain
      constraints. The approach is successfully tested in simulated and real tank
      phantoms. We compute the position error and resolution to compare the
      localization performance of the proposed method with the one-step Gauss-Newton
      reconstruction with Laplacian prior. We also study the effects of sensor position
      errors. Our results show that EIT spatial filtering is useful for localizing
      conductivity changes of relatively small size and for estimating their time
      courses. Some potential dynamic EIT applications such as acute ischemic stroke
      detection and neuronal activity localization may benefit from the higher
      resolution of spatial filters as compared to conventional tomographic
      reconstruction algorithms.

PMID- 25598004
TI  - Dramatic changes in muscle contractile and structural properties after 2
      botulinum toxin injections.
AB  - INTRODUCTION: Botulinum toxin is frequently administered serially to maintain
      therapeutic muscle paralysis, but the effect of repeated doses on muscle function
      are largely unknown. This study characterized the muscle response to 2
      onabotulinum toxin (BoNT) injections separated by 3 months. METHODS: Animal
      subjects received a single toxin injection (n = 8), 2 BoNT injections separated
      by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n =
      8). RESULTS: The functional effect of 2 serial injections was exponentially
      greater than the effect of a single injection. While both groups treated with a
      single BoNT injection had decreased torque in the injected leg by approximately
      50% relative to contralateral legs, the double BoNT injected group had decreased
      torque by over 95% relative to the preinjection level. Both single and double
      BoNT injections produced clear signs of fiber-type grouping. CONCLUSIONS: These
      experiments demonstrate a disproportionately greater effect of repeated BoNT
      injections.

PMID- 25598008
TI  - Effects of mineralocorticoid receptor antagonists in patients with preserved
      ejection fraction: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been shown to be
      effective in patients with heart failure or myocardial infarction complicated by
      a reduced ejection fraction. However, the role of MRAs in patients with preserved
      ejection fraction (PEF) remains to be clarified. We aimed to summarize the
      evidence for the efficacy of MRAs in patients with either heart failure with PEF
      (HF-PEF) or myocardial infarction with PEF (MI-PEF). METHODS: We searched PubMed,
      EMBASE, Cochrane Library, and clinical trials databases for randomized controlled
      trials, through June 2014, assessing MRA treatment in HF-PEF or MI-PEF patients.
      Fourteen randomized controlled trials (MI-PEF, 5; HF-PEF, 9; n = 6,428 patients)
      were included. RESULTS: MRA treatment reduced the risk of hospitalization for
      heart failure (relative risk, 0.83; 95% confidence interval [CI], 0.70 to 0.98),
      improved quality of life (weighted mean difference [WMD], -5.16; 95% CI, -8.03 to
      -2.30), left ventricular end-diastolic diameter (standardized mean difference, 
      0.21; 95% CI, 0.32 to -0.11), and serum amino-terminal peptide of procollagen
      type-III level (WMD, -1.50, 95% CI, -1.72 to -1.29) in patients with PEF. In
      addition, MRAs reduced E/e'(an echocardiographic estimate of filling pressure for
      assessment of diastolic function; WMD, -1.82; 95% CI, -2.23 to -1.42) in HF-PEF
      patients and E/A ratio (the ratio of early to late diastolic transmitral flow;
      WMD, 0.12; 95% CI, 0.10 to 0.14) in MI-PEF patients. However, all-cause mortality
      was not improved by MRAs in either HF-PEF (P = 0.90) or MI-PEF (P = 0.27)
      patients. CONCLUSIONS: MRA treatment in PEF patients led to reduced
      hospitalization for heart failure, quantifiable improvements in quality of life
      and diastolic function, and reversal of cardiac remodeling, but did not provide
      any all-cause mortality benefit.

PMID- 25598011
TI  - Histidine phosphocarrier protein regulates pyruvate kinase A activity in response
      to glucose in Vibrio vulnificus.
AB  - The bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) consists
      of two general energy-coupling proteins [enzyme I and histidine phosphocarrier
      protein (HPr)] and several sugar-specific enzyme IIs. Although, in addition to
      the phosphorylation-coupled transport of sugars, various regulatory roles of PTS
      components have been identified in Escherichia coli, much less is known about the
      PTS in the opportunistic human pathogen Vibrio vulnificus. In this study, we have
      identified pyruvate kinase A (PykA) as a binding partner of HPr in V. vulnificus.
      The interaction between HPr and PykA was strictly dependent on the presence of
      inorganic phosphate, and only dephosphorylated HPr interacted with PykA.
      Experiments involving domain swapping between the PykAs of V. vulnificus and E.
      coli revealed the requirement for the C-terminal domain of V. vulnificus PykA for
      a specific interaction with V. vulnificus HPr. Dephosphorylated HPr decreased the
      Km of PykA for phosphoenolpyruvate by approximately fourfold without affecting
      Vmax . Taken together, these findings indicate that the V. vulnificus PTS
      catalyzing the first step of glycolysis stimulates the final step of glycolysis
      in the presence of glucose through the direct interaction of dephospho-HPr with
      the C-terminal domain of PykA.

PMID- 25598010
TI  - Soil microbial community composition does not predominantly determine the
      variance of heterotrophic soil respiration across four subtropical forests.
AB  - To explore the importance of soil microbial community composition on explaining
      the difference in heterotrophic soil respiration (R(h)) across forests, a field
      investigation was conducted on Rh and soil physiochemical and microbial
      properties in four subtropical forests in southern China. We observed that Rh
      differed significantly among forests, being 2.48 +/- 0.23, 2.31 +/- 0.21, 1.83 +/
      0.08 and 1.56 +/- 0.15 MUmol m(-2) s(-1) in the climax evergreen broadleaf
      forest (BF), the mixed conifer and broadleaf forest (CF), the conifer plantation
      (CP), and the native broadleaved species plantation (BP), respectively. Both
      linear mixed effect model and variance decomposition analysis indicated that soil
      microbial community composition derived from phospholipid fatty acids (PLFAs) was
      not the first-order explanatory variable for the R(h) variance across the
      forests, with the explanatory power being 15.7%. Contrastingly, vegetational
      attributes such as root biomass (22.6%) and soil substrate availability (18.6%)
      were more important for explaining the observed R(h) variance. Our results
      therefore suggest that vegetation attributes and soil carbon pool size, rather
      than soil microbial community composition, should be preferentially considered to
      understand the spatial R(h) variance across the subtropical forests in southern
      China.

PMID- 25598009
TI  - In vitro and in vivo regulation of synaptogenesis by the novel antidepressant
      spadin.
AB  - BACKGROUND AND PURPOSE: We have described a novel antidepressant peptide, spadin,
      that acts by blocking the TWIK-related-potassium channel, type 1 (TREK-1). Here,
      we examined possible mechanisms of action of spadin at both molecular and
      cellular levels. EXPERIMENTAL APPROACHES: Effects of spadin were measured in
      primary cultures of neurons or tissues from mice injected i.v. with spadin.
      Western blots, qPCR, histochemical and electrophysiological techniques were used.
      KEY RESULTS: In vitro, spadin increased neuronal membrane potential and activated
      both the MAPK and PI3K signalling pathways, in a time- and concentration
      dependent manner. The latter pathway was involved in the protective effect of
      spadin against staurosporine-induced apoptosis. Also, spadin enhanced both mRNA
      expression and protein of two markers of synaptogenesis, the post-synaptic
      density protein of 95 kDalton (PSD-95) and synapsin. We confirmed these effects
      on synaptogenesis by the observation that spadin treatment significantly
      increased the proportion of mature spines in cortical neurons. Finally, in vivo
      injections of spadin led to a rapid increase in both mRNA expression and protein
      level of brain-derived neurotrophic factor (BDNF) in the hippocampus, confirming
      the antidepressant action of the peptide. We argue for a new role of spadin in
      synaptogenesis as both PSD-95 and synapsin mRNA expression and protein levels
      were further enhanced in the hippocampus, following treatment in vivo with the
      peptide. CONCLUSIONS AND IMPLICATIONS: These findings provide new mechanisms of
      action for the rapidly acting antidepressant peptide spadin by stimulating
      expression of BDNF and synaptic proteins, both in vitro and in vivo.

PMID- 25598012
TI  - Incidental diagnosis of diffuse intrinsic pontine glioma in children.
AB  - Children with diffuse intrinsic pontine glioma (DIPG) have a short onset, rapidly
      progressive neurologic decline before diagnosis. Therefore, incidental diagnosis
      of such an aggressive cancer is counterintuitive, yet our experience shows DIPG
      may occur as part of a spectrum of incidentally diagnosed pediatric brain
      cancers. Although children with incidentally diagnosed DIPG may experience a
      longer survival, it remains a potentially deadly cancer despite treatment with
      radiotherapy. Histologic confirmation is warranted when feasible in such patients
      to confirm diagnosis. Moreover, recent advances in genome-wide analyses may
      suggest incidentally diagnosed DIPGs are biologically distinct from the majority
      of these cancers.

PMID- 25598013
TI  - The efficacy and safety of inhaled human alpha-1 antitrypsin in people with alpha
      1 antitrypsin deficiency-related emphysema.
AB  - alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant condition
      characterized by low circulating levels of alpha-1 antitrypsin (AAT), a serine
      protease inhibitor. Significant work has been carried out in the development of
      AAT augmentation therapy for AATD. While the majority of this activity has
      focused on intravenous (iv.) augmentation, evidence of a significant clinical
      benefit is still debated and iv. therapy is expensive, onerous and time
      consuming. Inhalation therapy offers the opportunity for easier and more
      efficient delivery of AAT directly to the lungs with some evidence of a reduction
      in local inflammatory and proteolytic activity, potentially offering an
      alternative therapeutic option to the iv. route. There are, however, theoretical
      obstacles to the potential efficacy of aerosol-delivered AAT and although there
      have been a number of short-term studies examining inhaled AAT and its effect on
      lung inflammation, there has only been one long-term study to date in AATD
      looking at clinical outcomes, which is as yet unpublished. 

PMID- 25598014
TI  - House dust mite reduction and avoidance measures for treating eczema.
AB  - BACKGROUND: Eczema is an inflammatory skin disease that tends to involve skin
      creases, such as the folds of the elbows or knees; it is an intensely itchy skin
      condition, which can relapse and remit over time. As many as a third of people
      with eczema who have a positive test for allergy to house dust mite have reported
      worsening of eczema or respiratory symptoms when exposed to dust. OBJECTIVES: To
      assess the effects of all house dust mite reduction and avoidance measures for
      the treatment of eczema. SEARCH METHODS: We searched the following databases up
      to 14 August 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The
      Cochrane Library (2014, Issue 8), MEDLINE (from 1946), Embase (from 1974), LILACS
      (from 1982), and the GREAT database. We also searched five trials registers and
      checked the reference lists of included and excluded studies for further
      references to relevant studies. We handsearched abstracts from international
      eczema and allergy meetings. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) of any of the house dust mite reduction and avoidance measures for the
      treatment of eczema, which included participants of any age diagnosed by a
      clinician with eczema as defined by the World Allergy Organization. We included
      all non-pharmacological and pharmacological interventions that sought to reduce
      or avoid exposure to house dust mite and their allergenic faeces. The comparators
      were any active treatment, no treatment, placebo, or standard care only. DATA
      COLLECTION AND ANALYSIS: Two authors independently checked the titles and
      abstracts identified, and there were no disagreements. We contacted authors of
      included studies for additional information. We assessed the risk of bias using
      Cochrane methodology. MAIN RESULTS: We included seven studies of 324 adults and
      children with eczema. Overall, the included studies had a high risk of bias. Four
      of the seven trials tested interventions with multiple components, and three
      tested a single intervention. Two of the seven trials included only children,
      four included children and adults, and one included only adults. Interventions to
      reduce or avoid exposure to house dust mite included covers for mattresses and
      bedding, increased or high-quality vacuuming of carpets and mattresses, and
      sprays that kill house dust mites.Four studies assessed our first primary outcome
      of 'Clinician-assessed eczema severity using a named scale'. Of these, one study
      (n = 20) did not show any significant short-term benefit from allergen
      impermeable polyurethane mattress encasings and acaricide spray versus allergen
      permeable cotton mattress encasings and placebo acaricide spray. One study (n =
      60) found a modest statistically significant benefit in the Six Area, Six Sign
      Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95%
      confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable
      bedding system combined with benzyltannate spray and high-filtration vacuuming
      versus mite permeable cotton encasings, water with a trace of alcohol spray, and
      a low-filtration vacuum cleaner. The third study (n = 41) did not compare the
      change in severity of eczema between the two treatment groups. The fourth study
      (n = 86) reported no evidence of a difference between the treatment groups.With
      regard to the secondary outcomes 'Participant- or caregiver-assessed global
      eczema severity score' and the 'Amount and frequency of topical treatment
      required', one study (n = 20) assessed these outcomes with similar results being
      reported for these outcomes in both groups. Four studies (n = 159) assessed
      'Sensitivity to house dust mite allergen using a marker'; there was no clear
      evidence of a difference in sensitivity levels reported between treatments in any
      of the four trials.None of the seven included studies assessed our second primary
      outcome 'Participant- or caregiver-assessed eczema-related quality of life using
      a named instrument' or the secondary outcome of 'Adverse effects'.We were unable
      to combine any of our results because of variability in the interventions and
      paucity of data. AUTHORS' CONCLUSIONS: We were unable to determine clear
      implications to inform clinical practice from the very low-quality evidence
      currently available. The modest treatment responses reported were in people with
      atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus,
      their use in the eczema population as a whole is unknown. High-quality long-term
      trials of single, easy-to-administer house dust mite reduction or avoidance
      measures are worth pursuing.

PMID- 25598017
TI  - Asymmetric rhodium-catalyzed addition of thiols to allenes: synthesis of branched
      allylic thioethers and sulfones.
AB  - A highly regio- and enantioselective hydrothiolation of terminal allenes, a
      reaction which fulfills the criteria of atom economy, is reported. Applying two
      chiral rhodium catalyst systems, a wide variety of thiols and allenes could be
      coupled. Oxidation gave access to the corresponding allylic sulfones in
      essentially enantiomerically pure form. The reaction tolerates a variety of
      functional groups and labeling experiments gave first insights into the reaction
      mechanism of this new methodology. 

PMID- 25598015
TI  - Malignant peripheral nerve sheath tumor (MPNST) in the spine: a retrospective
      analysis of clinical and molecular prognostic factors.
AB  - Spinal malignant peripheral nerve sheath tumors (MPNSTs) are relatively rare.
      There is little information published in the literature regarding this subject.
      The aim of this retrospective study was to evaluate factors that may affect the
      outcomes of patients with spinal MPNSTs by reviewing 43 patients with spinal
      MPNST who were treated in our hospital between 2001 and 2012. Univariate and
      multivariate analyses were performed to identify prognostic variables relative to
      patient and tumor characteristics, treatment modality and molecules. All 43 MPNST
      patients (25 men and 18 women; median age 49 years) underwent surgical resection,
      of whom 15 patients also underwent postoperative radiotherapy. Local recurrence
      was found in 21 (48.8 %) patients. Twenty-two (51.2 %) patients died during the
      follow-up periods with a median survival time of 49 months. The 5-year recurrence
      and survival rate was 53 and 44 % respectively. The statistical analyses
      suggested that high-grade malignancy and osteolytic destruction were closely
      associated with recurrence and death. A total of 38 cases accepted postoperative
      immunohistochemisty examine. S-100 was identified as an independent factor
      related to both recurrence and survival, adjusting for clinical factors. In
      conclusion, we confirmed that malignant grade and osteolytic destruction were the
      two independent factors for both recurrence and survival, while patients with S
      100 protein negative had a higher recurrence rate and a lower survival rate.

PMID- 25598018
TI  - Arbitrary, direct and deterministic manipulation of vector beams via electrically
      tuned q-plates.
AB  - Vectorial vortex light beams, also referred to as spirally polarized beams, are
      of particular interest since they can be exploited in several applications
      ranging from quantum communication to spectroscopy and microscopy. In particular,
      symmetric pairs of vector beams define two-dimensional spaces which are described
      as "hybrid Poincare spheres" (HPS). While generation of vortex beams has been
      demonstrated by various techniques, their manipulation, in particular in order to
      obtain transformations describing curves entirely contained on a given HPS, is
      quite challenging, as it requires a simultaneous action on both polarization and
      orbital angular momentum degrees of freedom. Here, we demonstrate experimentally
      this kind of manipulation by exploiting electrically-tuned q-plates: an arbitrary
      transformation on the HPS can be obtained, by controlling two parameters of the q
      plate, namely the initial optic axis orientation alpha0 and the uniform
      birefringent phase retardation delta. Upon varying such parameters, one can
      determine both the rotation axis and the rotation angle on the HPS, obtaining the
      desired state manipulation with high fidelity. 

PMID- 25598019
TI  - Clinical applications of the pedicled anterolateral thigh flap in reconstruction.
AB  - BACKGROUND: Reconstruction of extensive defects of the lower abdomen,
      penoscrotum, trochanter, groin and knee without using complex microsurgery is a
      reconstructive challenge. Pedicled anterolateral thigh (ALT) flaps offer many
      advantages over other regional flaps for this purpose, such as the large skin
      area and soft-tissue availability, a remarkable pedicle length, and possessing
      multiple components and reliability. We present our experience of using pedicled
      ALT flaps for repairing various defects. METHODS: From September 2006 to December
      2013, 42 pedicled ALT flaps were used in 41 patients for defects of the lower
      abdomen (three patients), trochanter (26 patients), penoscrotum (10 patients),
      groin (one patient) and knee (one patient). Twenty-eight were men and 13 were
      women, and their mean age was 70.5 years (range, 22-103 years). The
      characteristics of the patients' age, sex, cause, flap size, flap component,
      follow-up and donor sites were recorded. RESULTS: The flap size ranged from 8 * 5
      cm (40 cm2 ) to 11 * 18 cm (198 cm2 ). The length of the pedicle ranged from 9 to
      16 cm, which was enough to reach the defect without tension. No surgery-related
      mortality occurred. In 34 flaps, donor sites were closed primarily and eight
      underwent split-skin grafting. Satisfactory coverage was achieved in all
      patients. CONCLUSION: Our experience has shown the wide arc of rotation, large
      skin replacement potential, multiple components and reliability of pedicled ALT
      flaps. They are technically simple to apply as myocutaneous/fasciocutaneous flaps
      with minimal donor site morbidity.

PMID- 25598020
TI  - Evaluation of subclinical endometritis and consequences on fertility in
      piedmontese beef cows.
AB  - Subclinical endometritis (SEM) is poorly investigated in beef cows, as stated in
      the literature. This project aims to evaluate the rate and the consequences of
      SEM in Piedmontese cows, with a focus on bacteriological findings and fertility
      parameters. Uterine cytology was performed for 97 subjects; a total of 31% of the
      cows were diagnosed as being positive for SEM and as having an 8% neutrophil
      (PMN) presence on the slide, which is considered as the best cut-off to diagnose
      the pathology. Only 13% of the cows positive for SEM were pregnant within 130 dpp
      and generally showed increases of 40 days in the partum to conception interval
      compared with the negative cows (142 vs 182, p = 0.01). Cows positive for both
      bacteriology and cytology showed a lower fertility than cows with only
      inflammation or only a bacterial presence (p = 0.0004). Bacterial isolation
      detected different species, but no difference in regard to the impact of these
      bacteria on SEM was shown. Parity, presence of calves, hygiene condition, age and
      number of service did not affect whether a cow was positive for subclinical
      endometritis (p < 0.05). The housing system (free stalls vs tie stalls) used
      seems to affect the SEM rate in Piedmontese cows; cows bred in tie stalls were
      more likely to be positive for SEM (OR = 2.2; p = 0.04). In conclusion, cytology
      seems to be a good technique for the diagnosis of subclinical endometritis in
      beef cows, and as in dairy cows, subclinical endometritis has a detrimental
      effect on fertility, causing an increase in partum to conception and a decrease
      in the rate of cows who become pregnant within 130 dpp, particularly for those
      cows housed in a tie stall.

PMID- 25598022
TI  - Mechanochemical activation and patterning of an adhesive surface toward
      nanoparticle deposition.
AB  - Mechanical pulling of adhesive tape creates radicals on the tape's surface. These
      radicals are capable of reducing metal salts to the corresponding metal
      nanoparticles. In this way, the mechanically activated tape can be decorated with
      various types of nanoparticles, including Au, Ag, Pd, or Cu. While retaining
      their mechanical properties and remaining "sticky," the tapes can exhibit new
      properties derived from the presence of metal nanoparticles (e.g.,
      bacteriostaticity, increased electrical conductivity). They can also be patterned
      with nanoparticles only at selective locations of mechanical activation. 

PMID- 25598021
TI  - Alcohol consumption and risk of heart failure: a dose-response meta-analysis of
      prospective studies.
AB  - AIMS: The aim of this study was to conduct a meta-analysis of prospective studies
      assessing the relationship between alcohol consumption and risk of heart failure
      (HF). METHODS AND RESULTS: We searched the PubMed database from inception to
      September 2014 and reviewed the reference list of relevant articles to identify
      prospective studies assessing the association between alcohol consumption and
      risk of HF. Study-specific relative risk (RR) estimates were combined using a
      random-effects meta-analysis. The meta-analysis included eight prospective
      studies, with a total of 202 378 participants and 6211 cases of HF. The pooled
      adjusted RRs of HF were 0.85 [95% confidence interval (CI) 0.78-0.93] for light
      to moderate alcohol consumption (<14 drinks/week) and 0.90 (95% CI 0.72-1.13) for
      high alcohol consumption (>=14 drinks/week) compared with non-drinkers. In a dose
      response meta-analysis, we observed a non-linear relationship between alcohol
      consumption and risk of HF (P for non-linearity = 0.001). Compared with non
      drinkers, the RRs (95% CI) across levels of alcohol consumption were 0.90 (0.84
      0.96) for 3 drinks/week, 0.83 (0.73-0.95) for 7 drinks/week, 0.84 (0.72-0.98) for
      10 drinks/week, 0.90 (0.73-1.10) for 14 drinks/week, and 1.07 (0.77-1.48) for 21
      drinks/week. CONCLUSION: Alcohol consumption in moderation is associated with a
      reduced risk of HF.

PMID- 25598023
TI  - The impact of MR CLEAN.

PMID- 25598024
TI  - Daily National Institutes of Health Stroke Scale examinations at stroke centers:
      why not do them?
AB  - The National Institutes of Health Stroke Scale was originally designed to
      stratify patients according to stroke severity for clinical trials, and now it is
      used to predict disposition and prognosticate functional outcome. Many
      researchers have also adopted it to trend patient progress over time and detect
      early neurologic deterioration. However, few investigators have reported its
      utility in monitoring the daily progress of patients hospitalized for stroke. In
      the present article, the authors discuss the advantages of daily National
      Institutes of Health Stroke Scale assessments and our clinical experience with
      this invaluable tool. 

PMID- 25598025
TI  - Revisiting cerebral postischemic reperfusion injury: new insights in
      understanding reperfusion failure, hemorrhage, and edema.
AB  - Cerebral postischemic reperfusion injury is defined as deterioration of ischemic
      brain tissue that parallels and antagonizes the benefits of restoring cerebral
      circulation after therapeutic thrombolysis for acute ischemic stroke. To
      understand the paradox of injury caused by treatment, we first emphasize the
      phenomenon in which recanalization of an occluded artery does not lead to tissue
      reperfusion. Additionally, no-reflow after recanalization may be due to injury of
      the neurovascular unit, distal microthrombosis, or both, and certainly worsens
      outcome. We examine the mechanism of molecular and subcellular damage in the
      neurovascular unit, notably oxidative stress, mitochondrial dysfunction, and
      apoptosis. At the level of the neurovascular unit, which mediates crosstalk
      between the damaged brain and systemic responses in blood, we summarize emerging
      evidence demonstrating that individual cell components play unique and cumulative
      roles that lead to damage of the blood-brain barrier and neurons. Furthermore, we
      review the latest developments in establishing a link between the immune system
      and microvascular dysfunction during ischemic reperfusion. Progress in assessing
      reperfusion injury has also been made, and we review imaging studies using
      various magnetic resonance imaging modalities. Lastly, we explore potential
      treatment approaches, including ischemic preconditioning, postconditioning,
      pharmacologic agents, and hypothermia. 

PMID- 25598026
TI  - Quadriparesis due to simultaneous occurrence of hemorrhagic and ischemic stroke.

PMID- 25598027
TI  - Reply from Lynch et al. to letter from Vedpathak and Shah regarding 'When should
      physical rehabilitation commence after stroke: a systematic review'.

PMID- 25598028
TI  - Vasomotor menopausal symptoms and risk of stroke among mid-aged women.

PMID- 25598029
TI  - The neglected strokes--cerebrovascular complications of neglected tropical
      diseases.

PMID- 25598030
TI  - Complete reversal of severe ADC lesion in left M1 occlusion.

PMID- 25598031
TI  - Repeat brain imaging after thrombolysis is important.

PMID- 25598032
TI  - Multiple cerebral hemorrhages associated with Friend leukemia integration 1
      (FLI1) positive cardiac angiosarcoma and left atrial thrombi.

PMID- 25598033
TI  - Using the full span of the SPAN-100 index to predict functional outcome in the
      CHIMES study.

PMID- 25598034
TI  - Cardioembolic stroke in the THRombolysis and STatins (THRaST) study.

PMID- 25598035
TI  - Synthesis, structure and properties of C3-symmetric heterosuperbenzene with three
      BN units.
AB  - The parent skeleton of BN heterocoronene with three BN units and C3 symmetry was
      synthesized as a model compound of BN-doped graphene. Further investigation of
      this graphene-type molecule revealed the important role of BN doping in opening
      the bandgap and modulating the electronic properties. 

PMID- 25598036
TI  - Recurrent anterior shoulder instability: a review of the Latarjet procedure and
      its postoperative rehabilitation.
AB  - The shoulder is the most common joint to dislocate in the human body, with the
      dislocation often occurring in the anterior direction. This injury frequently
      results in soft tissue injury (eg, labral tear, capsular stretching) or bone
      injury (eg, glenoid or humeral head bone loss), which commonly leads to
      persistent deficits of shoulder function and a high risk of subsequent
      instability episodes in young, active patients. Patients with a significant
      degree of glenoid bone loss (> 25%) may require surgical intervention using the
      Latarjet procedure, which is an open bony augmentation of the glenoid. This
      procedure involves transferring the tip of the coracoid to the anteroinferior
      glenoid, creating a bony block and musculotendinous sling to prevent instability.
      Rehabilitation after the procedure is a slow progression over 4 to 6 months to
      regain range of motion and strength, while protecting the bony augmentation.
      Recent reports have shown success with the Latarjet procedure, as indicated by
      patient satisfaction scores and a low rate of recurrent instability.

PMID- 25598037
TI  - Can we safely recommend gestational weight gain below the 2009 guidelines in
      obese women? A systematic review and meta-analysis.
AB  - A systematic review was conducted to determine the risk of adverse pregnancy
      outcomes with gestational weight gain (GWG) below the 2009 Institute of Medicine
      guidelines compared with within the guidelines in obese women. MEDLINE, Embase,
      Cochrane Register, CINHAL and Web of Science were searched from 1 January 2009 to
      31 July 2014. Quality was assessed using a modified Newcastle-Ottawa scale. Three
      primary outcomes were included: preterm birth, small for gestational age (SGA)
      and large for gestational age (LGA). Eighteen cohort studies were included. GWG
      below the guidelines had higher odds of preterm birth (adjusted odds ratio [AOR]
      1.46; 95% confidence interval [CI] 1.07-2.00) and SGA (AOR 1.24; 95% CI 1.13
      1.36) and lower odds of LGA (AOR 0.77; 95% CI 0.73-0.81) than GWG within the
      guidelines. Across the three obesity classes, the odds of SGA and LGA did not
      show any notable gradient and remained unexplored for preterm birth. Decreased
      odds were noted for macrosomia (AOR 0.64; 95% CI 0.54-0.77), gestational
      hypertension (AOR, 0.70; 95% CI 0.53-0.93), pre-eclampsia (AOR 0.90; 95% CI 0.82
      0.99) and caesarean (AOR 0.87; 95% CI 0.82-0.92). GWG below the guidelines cannot
      be routinely recommended but might occasionally be individualized for certain
      women, with caution, taking into account other known risk factors. 

PMID- 25598040
TI  - Prevalence of Internet gaming disorder in German adolescents: diagnostic
      contribution of the nine DSM-5 criteria in a state-wide representative sample.
AB  - BACKGROUND AND AIMS: Internet gaming disorder (IGD) is included as a condition
      for further study in Section 3 of the DSM-5. Nine criteria were proposed with a
      threshold of five or more criteria recommended for diagnosis. The aims of this
      study were to assess how the specific criteria contribute to diagnosis and to
      estimate prevalence rates of IGD based on DSM-5 recommendations. DESIGN: Large
      scale, state-representative school survey using a standardized questionnaire.
      SETTING: Germany (Lower Saxony). PARTICIPANTS: A total of 11 003 ninth-graders
      aged 13-18 years (mean = 14.88, 51.09% male). MEASUREMENTS: IGD was assessed with
      a DSM-5 adapted version of the Video Game Dependency Scale that covered all nine
      criteria of IGD. FINDINGS: In total, 1.16% [95% confidence interval (CI) = 0.96,
      1.36] of respondents were classified with IGD according to DSM-5 recommendations.
      IGD students played games for longer periods, skipped school more often, had
      lower grades in school, reported more sleep problems and more often endorsed
      feeling 'addicted to gaming' than their non-IGD counterparts. The most frequently
      reported DSM-5 criteria overall were 'escape adverse moods' (5.30%) and
      'preoccupation' (3.91%), but endorsement of these criteria rarely related to IGD
      diagnosis. Conditional inference trees showed that the criteria 'give up other
      activities', 'tolerance' and 'withdrawal' were of key importance for identifying
      IGD as defined by DSM-5. CONCLUSIONS: Based on a state-wide representative school
      survey in Germany, endorsement of five or more criteria of DSM-5 internet gaming
      disorder (IGD) occurred in 1.16% of the students, and these students evidence
      greater impairment compared with non-IGD students. Symptoms related to 'give up
      other activities', 'tolerance' and 'withdrawal' are most relevant for IGD
      diagnosis in this age group.

PMID- 25598039
TI  - Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience
      from 146,958 pregnancies.
AB  - OBJECTIVES: To report the clinical performance of massively parallel sequencing
      based non-invasive prenatal testing (NIPT) in detecting trisomies 21, 18 and 13
      in over 140,000 clinical samples and to compare its performance in low-risk and
      high-risk pregnancies. METHODS: Between 1 January 2012 and 31 August 2013,
      147,314 NIPT requests to screen for fetal trisomies 21, 18 and 13 using low
      coverage whole-genome sequencing of plasma cell-free DNA were received. The
      results were validated by karyotyping or follow-up of clinical outcomes. RESULTS:
      NIPT was performed and results obtained in 146,958 samples, for which outcome
      data were available in 112,669 (76.7%). Repeat blood sampling was required in
      3213 cases and 145 had test failure. Aneuploidy was confirmed in 720/781 cases
      positive for trisomy 21, 167/218 cases positive for trisomy 18 and 22/67 cases
      positive for trisomy 13 on NIPT. Nine false negatives were identified, including
      six cases of trisomy 21 and three of trisomy 18. The overall sensitivity of NIPT
      was 99.17%, 98.24% and 100% for trisomies 21, 18 and 13, respectively, and
      specificity was 99.95%, 99.95% and 99.96% for trisomies 21, 18 and 13,
      respectively. There was no significant difference in test performance between the
      72,382 high-risk and 40,287 low-risk subjects (sensitivity, 99.21% vs. 98.97% (P
      = 0.82); specificity, 99.95% vs. 99.95% (P = 0.98)). The major factors
      contributing to false-positive and false-negative NIPT results were maternal copy
      number variant and fetal/placental mosaicism, but fetal fraction had no effect.
      CONCLUSIONS: Using a stringent protocol, the good performance of NIPT shown by
      early validation studies can be maintained in large clinical samples. This
      technique can provide equally high sensitivity and specificity in screening for
      trisomy 21 in a low-risk, as compared to high-risk, population.

PMID- 25598041
TI  - Colorectal surgery for cancer in very elderly patient.

PMID- 25598042
TI  - Water soluble contrast enema examination of the integrity of the rectal
      anastomosis prior to loop ileostomy reversal may be superfluous.
AB  - PURPOSE: Defunctioning loop ileostomy in low anterior resection (LAR) is
      routinely used to reduce consequences of anastomotic leakage. The purpose of this
      study was to analyze which examination technique is optimal for evaluating the
      integrity of the anastomosis prior to loop ileostomy reversal. METHODS:
      Retrospective analysis of 95 patients who had been subjected to LAR at
      Helsingborg Hospital and Skane University Hospital, Sweden, was undertaken
      between January 2007 and June 2009. The examination techniques of the rectal
      anastomosis prior to reversal and the clinical outcome after reversal were
      studied. RESULTS: Radiologic anastomosis control using water soluble contrast
      enema, digital rectal examination (DRE), and rectoscopy were performed in 53 %
      (50/95), 98 % (93/95), and 69 % (66/95), respectively. In two patients, no
      control of the anastomosis was performed before reversal. Fifty-two percent
      (49/95) of the patients were examined using all techniques. Six patients
      demonstrated leakage detected before reversal of which two were only radiological
      leakages. These two patients underwent loop ileostomy reversal after delay
      without complications. They were the only ones where the three examination
      techniques did not prove coherence. Four patients had symptomatic leakage; these
      were detected with rectoscopy and DRE and verified with enema. Three patients
      developed anastomotic leakage after loop ileostomy reversal despite normal
      preoperative examinations. Two of these patients had rectovaginal fistulas
      (AVFs). CONCLUSIONS: This retrospective study indicates that contrast enema does
      not provide additional information if rectoscopy and DRE are normal. Despite
      negative examinations, three of nine leakages were diagnosed after loop ileostomy
      reversal. Especially, AVFs seem difficult to diagnose.

PMID- 25598044
TI  - A case of newly diagnosed ulcerative colitis presenting with pseudo-membranous
      enterocolitis followed by CMV colitis complicated with rupture of mitral corda
      tendinea.

PMID- 25598043
TI  - Increased pre-surgical numbers of endothelial progenitor cells and circulating
      endothelial cells in colorectal cancer fail to predict outcome.
AB  - INTRODUCTION: The endothelium and angiogenesis are therapeutic targets in cancer.
      Response to treatment may be assessed by laboratory plasma markers such as
      circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), von
      Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor
      (VEGF) and angiogenin. We hypothesised that these markers, obtained before
      surgery, would predict 2-year outcome after surgery with or without anti
      angiogenic therapy for colorectal cancer (CRC). METHODS: We recruited 154
      patients with CRC, of whom 51 were treated with surgery alone, 74 were treated
      with standard chemotherapy (5-fluorouracil) and 29 were treated with standard
      chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before
      surgery. CD34(+)/CD45(-)/CD146(+) CECs and CD34(+)/CD45(-)/CD309 [KDR](+) EPCs
      were measured by flow cytometry and plasma markers by ELISA. RESULTS: After a
      mean of 2.1 years follow-up (range 1.9-2.3 years), 52 of the patients (33.7 %)
      experienced a poor outcome (radiological and/or histological evidence of tumour
      spread or recurrence, or death [n = 26]). In univariate analysis, poor outcome
      was linked to Dukes' stage (p < 0.001), American Joint Committee on Cancer (AJCC)
      stage (p < 0.001), type of treatment (surgery alone, standard chemotherapy with
      or without anti-antigenic therapy) (p = 0.047), CECs (p < 0.02) and EPCs (p <
      0.01). In subsequent binary logistic regression analysis, only Dukes' stage
      (hazard ratio 2.3, 95 % confidence interval 1.0-5.3, p = 0.047) and modified AJCC
      stage (4.62, 1.88-11.33, p < 0.001) predicted a poor outcome. CONCLUSION:
      Endothelial cell markers (CECs, EPCs, vWf, soluble E selectin) and growth factors
      (VEGF and angiogenin), measured before surgery, have nothing extra to offer in
      predicting 2-year outcome in colorectal cancer when compared to Dukes' or AJCC
      stage.

PMID- 25598045
TI  - Letter to the editor: one point cancer of ileal adenocarcinoma complicated from
      Crohn's disease.

PMID- 25598046
TI  - In reply to Tin et al.

PMID- 25598047
TI  - Evaluation of the intestinal blood flow near the rectosigmoid junction using the
      indocyanine green fluorescence method in a colorectal cancer surgery.
AB  - PURPOSE: It has been reported that some patients do not have an anastomosis of a
      marginal artery near the rectosigmoid junction, but the frequency of this
      condition and its clinical significance so far remain unclear. The aim of this
      study was to evaluate the blood flow at the marginal artery near the rectosigmoid
      junction. METHODS: From January 2013 to January 2014, we enrolled consecutive
      patients with a preoperative diagnosis of left-sided colon cancer or rectal
      cancer who underwent surgery with lymph node dissection. During the operation,
      the blood flow through the point of origin of the last sigmoid arterial branch,
      originating from the inferior mesenteric artery, was interrupted, and the
      rectosigmoid junction was supplied by only the marginal artery. We injected
      indocyanine green intravenously and observed the blood flow using a near-infrared
      camera system. RESULTS: A total of 119 consecutive patients were enrolled in this
      study. Sixty-eight patients (57.1 %) had a good anastomosis of the marginal
      artery near the rectosigmoid junction (type A). In 27 patients (22.7 %), a
      fluorescence border was recognized, but the fluorescence border diminished within
      60 s (Type B). In 18 patients (15.1 %), delayed fluorescence was recognized over
      60 s (type C), and 6 patients (5.0 %) had no fluorescence at all (type D). A mean
      length of 14.8 cm was found from the peritoneal reflection to fluorescence border
      of blood flow. CONCLUSIONS: This study proves that cases without the anastomosis
      of the marginal artery of the rectosigmoid junction truly exist, using studies in
      living humans (UMIN000011186).

PMID- 25598048
TI  - Professional ethics in nursing: an integrative review.
AB  - AIM: To conduct an integrative review and synthesize current primary studies of
      professional ethics in nursing. BACKGROUND: Professional ethics is a familiar
      concept in nursing and provides an ethical code for nursing practice. However,
      little is known about how professional ethics has been defined and studied in
      nursing science. DESIGN AND DATA SOURCES: Systematic literature searches from
      1948-February 2013, using the CINAHL, PubMed and Scopus electronic databases to
      look at previously published peer-reviewed studies. REVIEW METHOD: A modified
      version of Cooper's five-stage integrative review was used to review and
      synthesize current knowledge. RESULTS: Fourteen papers were included in this
      research. According to our synthesis, professional ethics is described as an
      intra-professional approach to care ethics and professionals commit to it
      voluntarily. Professional ethics consist of values, duties, rights and
      responsibilities, regulated by national legislation and international agreements
      and detailed in professional codes. Professional ethics is well established in
      nursing, but is constantly changing due to internal and external factors
      affecting the profession. CONCLUSION: Despite the obvious importance of
      professional ethics, it has not been studied much in nursing science. Greater
      knowledge of professional ethics is needed to understand and support nurses'
      moral decision-making and to respond to the challenges of current changes in
      health care and society.

PMID- 25598049
TI  - Long-term experience with Chinese language shapes the fusiform asymmetry of
      English reading.
AB  - Previous studies have suggested differential engagement of the bilateral fusiform
      gyrus in the processing of Chinese and English. The present study tested the
      possibility that long-term experience with Chinese language affects the fusiform
      laterality of English reading by comparing three samples: Chinese speakers,
      English speakers with Chinese experience, and English speakers without Chinese
      experience. We found that, when reading words in their respective native
      language, Chinese and English speakers without Chinese experience differed in
      functional laterality of the posterior fusiform region (right laterality for
      Chinese speakers, but left laterality for English speakers). More importantly,
      compared with English speakers without Chinese experience, English speakers with
      Chinese experience showed more recruitment of the right posterior fusiform cortex
      for English words and pseudowords, which is similar to how Chinese speakers
      processed Chinese. These results suggest that long-term experience with Chinese
      shapes the fusiform laterality of English reading and have important implications
      for our understanding of the cross-language influences in terms of neural
      organization and of the functions of different fusiform subregions in reading. 

PMID- 25598051
TI  - Design of a microfluidic device for comprehensive spatial two-dimensional liquid
      chromatography.
AB  - This study discusses the design aspects for the construction of a microfluidic
      device for comprehensive spatial two-dimensional liquid chromatography. In
      spatial two-dimensional liquid chromatography each peak is characterized by its
      coordinates in the plane. After completing the first-dimension separation all
      fractions are analyzed in parallel second-dimension separations. Hence, spatial
      two-dimensional liquid chromatography potentially provides much higher peak
      production rates than a coupled column multi-dimensional liquid chromatography
      approach in which the second-dimension analyses are performed sequentially. A
      chip for spatial two-dimensional liquid chromatography has been manufactured from
      cyclic olefin copolymer and features a first-dimension separation channel and 21
      parallel second-dimension separation channels oriented perpendicularly to the
      former. Compartmentalization of first- and second-dimension developments by
      physical barriers allowed for a preferential flow path with a minimal dispersion
      into the second-dimension separation channels. To generate a homogenous flow
      across all the parallel second-dimension channels, a radially interconnected flow
      distributor containing two zones of diamond-shaped pillars was integrated on
      chip. A methacrylate ester based monolithic stationary phase with optimized
      macroporous structure was created in situ in the confines of the microfluidic
      chip. In addition, the use of a photomask was explored to localize monolith
      formation in the parallel second-dimension channels. Finally, to connect the
      spatial chip to the liquid chromatography instrument, connector ports were
      integrated allowing the use of Viper fittings. As an alternative, a chip holder
      with adjustable clasp locks was designed that allows the clamping force to be
      adjusted. 

PMID- 25598052
TI  - Mechanisms of and strategies for overcoming resistance to anti-vascular
      endothelial growth factor therapy in non-small cell lung cancer.
AB  - Sustained angiogenesis is a hallmark of cancer. Because of the primary role of
      vascular endothelial growth factors (VEGFs) and their receptors in angiogenesis,
      VEGF-targeted agents have been developed to inhibit these signaling processes in
      non-small cell lung cancer (NSCLC). However, the clinical benefits are transient
      and resistance often rapidly develops. Insights into the molecular mechanisms of
      resistance would help to develop novel strategies to improve the efficacy of
      antiangiogenic therapies. This review discusses the mechanisms of resistance to
      anti-VEGF therapy and the postulated strategies to optimize antiangiogenic
      therapy. A number of multitargeted tyrosine kinase inhibitors currently in phase
      III clinical development for NSCLC are summarized. The emerging combination of
      antiangiogenic therapy with tumor immunotherapy is also discussed. 

PMID- 25598053
TI  - Surgical complications after kidney transplantation: different impacts of
      immunosuppression, graft function, patient variables, and surgical performance.
AB  - The population of kidney transplant (KTx) recipients often has complex medical
      and immunological conditions. Surgical complications (SCs) contribute to the
      increasing morbidity and costs in these patients. We analyzed the risk factors
      for SC in 405 KTx patients treated using defined immunosuppressive regimens
      according to their clinical and immunological risk profile: (1) standard
      immunosuppression (SIS) with IL-2 receptor mAb, CNI, and (a) mycophenolic acid
      (MPA) or (b) mTOR inhibitor; and (2) more intense immunosuppression (IIS) with
      (a) ATG or (b) the additional use of plasma exchange and B- and T-cell-depleting
      agents. In a mixed effects logistic regression model, we identified the following
      risk factors for SC: male gender, diabetes, and post-operative dialysis. No
      difference was found between the patients who received SIS with MPA and those who
      received mTOR inhibitors. The risk of suffering complications with IIS increases
      with age. In addition to IIS, diabetes was a risk for wound healing disorders.
      Therapeutic anticoagulation and a third or subsequent retransplantation increased
      the rate of bleeding. We did not identify immunosuppression or patient
      demographics as risk factors for lymphoceles or ureter complications; however, we
      demonstrated that the surgeon had a significant impact on severe complications,
      especially those of the ureter. 

PMID- 25598050
TI  - Large-scale probabilistic functional modes from resting state fMRI.
AB  - It is well established that it is possible to observe spontaneous, highly
      structured, fluctuations in human brain activity from functional magnetic
      resonance imaging (fMRI) when the subject is 'at rest'. However, characterising
      this activity in an interpretable manner is still a very open problem. In this
      paper, we introduce a method for identifying modes of coherent activity from
      resting state fMRI (rfMRI) data. Our model characterises a mode as the outer
      product of a spatial map and a time course, constrained by the nature of both the
      between-subject variation and the effect of the haemodynamic response function.
      This is presented as a probabilistic generative model within a variational
      framework that allows Bayesian inference, even on voxelwise rfMRI data.
      Furthermore, using this approach it becomes possible to infer distinct extended
      modes that are correlated with each other in space and time, a property which we
      believe is neuroscientifically desirable. We assess the performance of our model
      on both simulated data and high quality rfMRI data from the Human Connectome
      Project, and contrast its properties with those of both spatial and temporal
      independent component analysis (ICA). We show that our method is able to stably
      infer sets of modes with complex spatio-temporal interactions and spatial
      differences between subjects. 

PMID- 25598054
TI  - Inguinal hernia repair: toward Asian guidelines.
AB  - Groin hernias are very common, and surgical treatment is usually recommended. In
      fact, hernia repair is the most common surgical procedure performed worldwide. In
      countries such as the USA, China, and India, there may easily be over 1 million
      repairs every year. The need for this surgery has become an important
      socioeconomic problem and may affect health-care providers, especially in aging
      societies. Surgical repair using mesh is recommended and widely employed in
      Western countries, but in many developing countries, tissue-to-tissue repair is
      still the preferred surgical procedure due to economic constraints. For these
      reason, the development and implementation of guidelines, consensus, or
      recommendations may aim to clarify issues related to best practices in inguinal
      hernia repair in Asia. A group of Asian experts in hernia repair gathered
      together to debate inguinal hernia treatments in Asia in an attempt to reach some
      consensus or develop recommendations on best practices in the region. The need
      for recommendations or guidelines was unanimously confirmed to help overcome the
      discrepancy in clinical practice between countries; the experts decided to focus
      mainly on the technical aspects of open repair, which is the most common surgery
      for hernia in our region. After the identification of 12 main topics for
      discussion (indication, age, and sex; symptomatic and asymptomatic hernia: type
      of hernia; type of treatment; hospital admission; preoperative care; anesthesia;
      surgical technique; perioperative care; postoperative care; early complications;
      and long-term complications), a search of the literature was carried out
      according to the five levels of the Oxford Classification of Evidence and the
      four grades of recommendation. 

PMID- 25598055
TI  - Three-dimensional fusion images combining CT gastrography and CT angiography for
      early gastric cancer: pilot experiences of preoperative simulation prior to
      totally laparoscopic gastrectomy.
AB  - We herein report two cases of gastric cancer in which preoperative 3-D CT
      gastrography and CT angiography fusion images enabled totally laparoscopic
      gastrectomy. Case 1 involved a 60-year-old woman with a superficial depressed
      lesion on the greater curvature of the middle gastric body. Case 2 involved a 64
      year-old woman with a superficial depressed lesion on the posterior wall of the
      upper gastric body. In both cases, 3-D fusion images were prepared from enhanced
      CT scans after the area near the lesions was clipped under preoperative
      gastroendoscopy. Based on the relative position between the clips and nearby
      vessels, a resection line was preoperatively determined in each case. Totally
      laparoscopic distal gastrectomy and totally laparoscopic proximal gastrectomy
      were performed in cases 1 and 2, respectively, with safe surgical margins. Three
      dimensional fusion images can help in preoperative simulation of totally
      laparoscopic gastrectomy. 

PMID- 25598056
TI  - Staging laparoscopy leads to rapid induction of chemotherapy for unresectable
      pancreatobiliary cancers.
AB  - Preoperatively evaluating the resectability of pancreatobiliary cancers is
      difficult. The aim of this study was to investigate the benefit of staging
      laparoscopy in unresectable pancreatobiliary cancers. Between 2010 and 2013, 25
      patients with pancreatobiliary cancers underwent staging laparoscopy after
      conventional tumor staging; they were compared with 10 patients who had
      unresectable or metastatic tumors that were found during laparotomy. Staging
      laparoscopy did not show unresectable factors in 11 patients, and resections were
      performed in these patients. Unresectable factors were found in other 14 patients
      who underwent staging laparoscopy. In these patients, chemotherapy was started
      after median postoperative day 3 (range, 2-10 days). This period was
      significantly longer in patients who received unnecessary laparotomy;
      chemotherapy was started after median postoperative day 11 (range, 6-15 days).
      These results suggest that staging laparoscopy, while avoiding laparotomy with
      unsuccessful resection, can lead to rapid induction of chemotherapy for
      unresectable pancreatobiliary cancers. 

PMID- 25598057
TI  - Osseous metaplasia of the endometrium and successful hysteroscopic resection: a
      report of two cases and a review of the literature.
AB  - Osseous metaplasia is a rare disorder of the endometrium that usually leads to
      secondary infertility and is frequently associated with recurrent abortions. Here
      we present two cases: one presenting with primary infertility and another
      presenting with oligomenorrhea. In both cases, vaginal ultrasonography showed an
      intrauterine structure that appeared hyperechogenic, suggesting calcification.
      Hysteroscopy revealed multiple white spicules of bony material in the uterine
      cavity. In both cases, the lesion was treated by hysteroscopic removal without
      complications. Histology established a diagnosis of endometrial osseous
      metaplasia. Thus, hysteroscopy was effective in the diagnosis and treatment of
      endometrial osseous metaplasia. The patient with primary infertility had
      spontaneous conception of twins 6 months after the procedure. 

PMID- 25598058
TI  - Superior mesenteric artery syndrome treated with single-incision laparoscopy
      assisted duodenojejunostomy.
AB  - Superior mesenteric artery (SMA) syndrome is an uncommon disease resulting from
      compression and partial obstruction of the third portion of the duodenum from the
      SMA. A 77-year-old man, who did not have a history of surgery, experienced
      repeated vomiting and developed abdominal distension. Abdominal CT showed a
      narrowed third portion of the duodenum, with a distended stomach and proximal
      duodenum. The patient was diagnosed as having SMA syndrome and was initially
      treated conservatively, but his condition did not improve. Single-incision
      laparoscopy-assisted duodenojejunostomy was performed. The patient recovered well
      and was discharged from hospital on postoperative day 8. Laparoscopic treatment
      is feasible for the treatment of SMA syndrome given its safety and minimal
      invasiveness. This is a report of the first case of single-incision laparoscopy
      assisted duodenojejunostomy. This procedure is safer and less invasive than a
      conventional laparoscopic approach in a patient with SMA syndrome. 

PMID- 25598059
TI  - Intraoperative fluorescent cholangiography using indocyanine green for
      laparoscopic fenestration of nonparasitic huge liver cysts.
AB  - Bile duct injury is one of the known serious complications of laparoscopic
      fenestration for nonparasitic liver cysts. Herein, we report the case of a huge
      liver cyst for which we performed laparoscopic fenestration using intraoperative
      fluorescent cholangiography with indocyanine green. A 71-year-old woman with
      abdominal distention was referred to our hospital. CT demonstrated a 17 * 11.5-cm
      simple cyst replacing the right lobe of the liver, so laparoscopic fenestration
      was performed. Although the biliary duct could not be detected because of
      compression by the huge cyst, fluorescent cholangiography with indocyanine green
      through endoscopic naso-biliary drainage tube clearly delineated the intrahepatic
      bile duct in the remaining cystic wall. The patient had no complications at 3
      months after surgery. Fluorescent cholangiography using indocyanine green is a
      safe and effective procedure to avoid bile duct injury during laparoscopic
      fenestration, especially in patients with a huge liver cyst. 

PMID- 25598060
TI  - Laparoscopic repair for intraoperative injury of the right hepatic artery during
      cholecystectomy.
AB  - Right hepatic artery (RHA) injury is a complication that occurs during
      laparoscopic cholecystectomy, which can sometimes cause hepatic artery
      pseudoaneurysm or ischemic hepatic necrosis. Therefore, RHA should be managed
      carefully. Herein, we report a case of intraoperative RHA injury that was
      successfully repaired during laparoscopic cholecystectomy. Bleeding was
      controlled prior to the cholecystectomy with vascular clamp forceps that had been
      inserted through an additional trocar, and repair of the RHA injury was then
      performed laparoscopically. The postoperative course was uneventful, and patency
      of the RHA and its sectional arteries were confirmed by CT arteriography.
      Laparoscopic repair of minor RHA injuries can be managed safely if bleeding is
      adequately controlled. 

PMID- 25598061
TI  - Retroperitoneal schwannomas: advantages of laparoscopic resection. Review of the
      literature and case presentation of a large paracaval benign schwannoma (with
      video).
AB  - Retroperitoneal schwannomas represent 0.5%-3% of all retroperitoneal tumors.
      Complete surgical removal is the treatment of choice because it permits a correct
      histological diagnosis and prevents eventual degeneration. Laparoscopic surgery
      has been reported as safe and effective by several authors. We present a
      comprehensive review of the literature regarding the role of laparoscopy in
      surgical resection of retroperitoneal schwannomas, and we present a case showing
      the technique (with video). Laparoscopic resection in experienced hands is safe
      and effective, and guarantees excellent postoperative results in terms of patient
      recovery. 

PMID- 25598062
TI  - Single-incision laparoscopic totally extraperitoneal obturator hernia repair in a
      patient on antiplatelet therapy: a case report.
AB  - An 83-year-old woman who complained of right lower limb discomfort was diagnosed
      with a right obturator hernia by CT scan. On examination, she had a soft and flat
      abdomen without signs of peritoneal irritation. The Howship-Romberg sign was
      present. She had a history of vasospastic angina and paroxysmal supraventricular
      tachycardia, and took aspirin and dipyridamole until she was admitted to the
      hospital. Exploratory laparoscopy identified a spontaneously reduced small bowel
      from the right obturator canal, but there were no signs of ischemic and necrotic
      bowel. The patient underwent SILS for totally extraperitoneal obturator hernia
      repair without a dissection balloon. The patient recovered without perioperative
      complications such as hemorrhage and thrombotic episodes. She remains well, and
      CT scans showed no signs of obturator hernia recurrence at the 7-month follow-up.

PMID- 25598063
TI  - Right paraduodenal hernia successfully treated with laparoscopic surgery.
AB  - A 23-year-old Japanese man presented with a history of sudden-onset right
      abdominal pain accompanied by nausea and vomiting. Contrast-enhanced CT showed a
      large cluster on the right side of the retroperitoneum, with most of the small
      bowel incarcerated. The patient was diagnosed with small bowel obstruction caused
      by a right paraduodenal hernia, and emergency laparoscopic surgery was performed.
      The large retroperitoneal cluster on the right side contained almost all segments
      of the small bowel, although the incarcerated bowel showed no evidence of
      volvulus or ischemia. The bowel was reduced, and the hernia orifice was closed.
      The patient made good progress and was discharged 7 days after surgery. We herein
      report an acute case of right paraduodenal hernia with small bowel obstruction
      that was successfully treated with emergency laparoscopic surgery. With an early
      preoperative diagnosis, laparoscopic surgery is appropriate for the treatment of
      right paraduodenal hernia. 

PMID- 25598064
TI  - Effective use of a vessel-sealing system for laparoscopic unroofing of liver
      cysts.
AB  - INTRODUCTION: Liver cysts that present with symptoms such as jaundice, abdominal
      pain, and intra-cystic infection require treatment. In laparoscopic unroofing of
      liver cysts, appropriate treatment is needed in cases where the cystic walls
      contain vessels or bile ducts. A vessel-sealing system can seal not only vessels,
      but also bile ducts. We experienced four cases in which laparoscopic unroofing of
      liver cysts was performed with a vessel-sealing system. MATERIALS AND SURGICAL
      TECHNIQUE: Case 1 was a woman in her 70s who presented at our hospital with
      abdominal pressure. Abdominal CT showed liver cysts with a maximum diameter of 13
      cm. Laparoscopic unroofing was performed with LigaSure Impact. Case 2 was a woman
      in her 50s with abdominal discomfort. CT showed a cyst 15 cm in diameter situated
      in the right lobe. We performed SILS using a LigaSure Blunt Tip to unroof the
      cyst. Case 3 was a man in his 80s with abdominal pain. CT showed a huge cyst 25
      cm in diameter in the right lobe. We performed hybrid SILS with a LigaSure Blunt
      Tip to unroof the cysts. Case 4 was a woman in her 70s with upper abdominal pain.
      CT showed multiple cysts with a maximum diameter of 15 cm in the bilateral lobes.
      We performed hybrid SILS to successfully unroof her cysts. None of the cases
      experienced postoperative complications, such as bleeding or bile leakage, and
      none experienced recurrence of cysts. DISCUSSION: A laparoscopic unroofing using
      a vessel-sealing system can be a minimally invasive and safe treatment for liver
      cysts.

PMID- 25598065
TI  - Laparoendoscopic removal of peroral extrusion of a ventriculoperitoneal shunt.
AB  - INTRODUCTION: Ventriculoperitoneal shunts for hydrocephalic children are known to
      cause serious complications such as GI perforation. Peroral extrusion of the
      peritoneal part of a ventriculoperitoneal shunt is very rare, and management
      could be a challenge. MATERIALS AND SURGICAL TECHNIQUE: An 11-year-old girl
      presented with peroral extrusion of the distal end of a ventriculoperitoneal
      shunt tube. Endoscopy and imaging studies showed that the peritoneal end had
      perforated the stomach and then extruded from the mouth. We used a surgical
      technique that combined endoscopy and laparoscopy to manage this rare
      complication. DISCUSSION: Peroral extrusion of a ventriculoperitoneal shunt tube
      occurs secondary to perforation of the upper GI tract. Managing this condition
      involves removing the shunt tube, attention to the perforated viscus and
      associated infection. A combination of endoscopy and laparoscopy provided
      superior views, enabled identification of the site and size of the perforated
      viscus, and facilitated the uneventful removal of the tube.

PMID- 25598066
TI  - New suture: tail clinch knot for transabdominal preperitoneal hernia repair.
AB  - INTRODUCTION: There is some controversy regarding the proper surgical method for
      inguinal hernia repair and whether transabdominal preperitoneal or totally
      extraperitoneal repair should be used. The greatest difference between these
      procedures is the need for absorbable sutures to close the peritoneal incision.
      MATERIALS AND SURGICAL TECHNIQUE: The clinch knot is a kind of slip knot that is
      used for securing a fishing lure, hook, or swivel to a fishing line. This knot is
      used by fishermen and has historically proven to be secure. DISCUSSION: When a
      clinch knot is placed at the tail end of a suture thread, a running suture can be
      started without knot tying.

PMID- 25598067
TI  - Re: Postoperative pain between single-incision and conventional laparoscopic
      appendectomy.

PMID- 25598068
TI  - Response to Re: Postoperative pain between single-incision and conventional
      laparoscopic appendectomy.

PMID- 25598069
TI  - Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro
      maturation.
AB  - Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell
      cycle checkpoints, and apoptosis. Significant effort has focused on elucidating
      the relationship between ATM and other nuclear signal transducers; however,
      little is known about the connection between ATM and oocyte meiotic maturation.
      We investigated the function of ATM in porcine oocytes. ATM was expressed at all
      stages of oocyte maturation and localized predominantly in the nucleus.
      Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte
      maturation, reducing the percentages of oocytes that underwent germinal vesicle
      breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the
      expression of DNA damage-related genes (breast cancer 1, budding uninhibited by
      benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and
      other cell cycle-regulated genes that are predominantly expressed during G2/M
      phase, including bone morphogenetic protein 15, growth differentiation factor 9,
      cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased
      the developmental potential of blastocysts following parthenogenetic activation
      and increased the level of apoptosis. Together, these data suggested that ATM
      influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially
      by decreasing their sensitivity to DNA strand breaks, stimulating the AKT
      pathway, and/or altering the expression of other maternal genes. 

PMID- 25598070
TI  - Numerical investigations of pulsatile flow in stenosed artery.
AB  - PURPOSE: Abnormalities in blood vessels by virtue of complex blood flow dynamics
      is being supported by non-Newtonian behavior of blood. Thus it becomes a focus of
      research to most of the researchers. Additionally, consideration of real life
      patient specific model of vessel as well as patient specific inlet flow boundary
      condition implementation was limited in literature. Thus a thorough
      implementation of these considerations was done here. METHOD: In this work, a
      numerical investigation of hemodynamic flow in stenosed artery has been carried
      out with realistic pulsating profile at the inlet. Flow has been considered to be
      laminar due to arresting condition of cardiovascular state of the subject. Two
      non- Newtonian rheological models namely, Power Law viscosity model and Quemada
      viscosity model have been used. Two different patient- specific pulsatile
      profiles are considered at the inlet of a long stenosed artery with varying
      degree of stenoses from 25% to 80%. RESULTS: Transient form of Navier-Stokes
      equation is solved in an axi-symmetric domain to calculate the detailed flow
      structure of the flow field. From the simulation data, temporal and time averaged
      wall shear stress, oscillatory shear index and pressure drop are calculated.
      CONCLUSIONS: The results demonstrate that oscillatory shear index and wall shear
      stresses are extensively governed by the degree of stenoses. The position and
      movement of recirculation bubbles are found to vary with flow Reynolds number.

PMID- 25598071
TI  - Wear and biological effects of a semi-constrained total disc replacement subject
      to modified ISO standard test conditions.
AB  - Development of pre-clinical testing methodologies is an important goal for
      improving prediction of artificial replacement joint performance and for guiding
      future device design. Total disc replacement wear and the potential for
      osteolysis is a growing concern, therefore a parametric study on the effects on
      wear of altered kinematics and loading was undertaken. A standard ISO testing
      protocol was modified in order to study the wear behaviour of lumbar total disc
      replacements when subject to low cross shear input kinematics, reduced axial
      loading and smaller flexion-extension magnitude. Volumetric wear, bearing surface
      topography, and wear debris biological reactivity were assessed. The ISO standard
      results were expected, however, the very low cross shear test produced a level of
      wear approximately two orders of magnitude higher than that reported for zero
      cross shear motions on UHMWPE bearings. When the osteolytic potential of the wear
      particles was calculated, all total disc replacement simulations had lower
      predicted osteolytic potential compared to total hip replacements, as a
      consequence of the generally lower wear rates found. 

PMID- 25598072
TI  - Prominent reinforcing effect of chitin nanocrystals on electrospun polydioxanone
      nanocomposite fiber mats.
AB  - The ultra-strong nanocomposite fiber mats based on biodegradable polydioxanone
      (PDO) and chitin nanocrystals (ChiNCs) were successfully prepared by means of
      electrospinning. The ChiNCs are uniformly dispersed in the PDO matrix and mostly
      oriented along fiber long axis, resulting in a significant improvement in
      mechanical property. Moreover, the introduction of ChiNCs led to the increase of
      the glass-transition temperature (Tg) and thermal decomposition temperature (Td)
      of PDO elucidated by thermal analyses. In addition, the loading of ChiNCs caused
      very different In vitro degradation behavior compared to neat PDO fiber mat.
      Furthermore, in vitro cell culture results indicated that the addition of ChiNCs
      improved the cellular adhesion and proliferation. 

PMID- 25598073
TI  - Isoflurane does not protect from brain death-associated aggravation of cold
      hepatic ischemia-reperfusion injury.
AB  - BACKGROUND: Previous studies have shown that brain death aggravates cold ischemia
      reperfusion injury in liver transplantation. Isoflurane, a volatile anesthetic,
      has been indicated to reduce warm hepatic ischemia-reperfusion injury. Herein, we
      studied in Sprague-Dawley rats whether isoflurane is capable of ameliorating
      brain death-associated aggravation of cold hepatic ischemia-reperfusion injury.
      MATERIAL AND METHODS: Brain-dead animals were treated for 30 min with isoflurane
      (MAC 1.5%; n=8). Animals without isoflurane treatment served as controls (n=8).
      Another 13 animals without induction of brain death served as sham controls.
      After a 4-h period portal venous blood perfusion, hepatic microcirculation and
      bile flow were determined. Livers were recovered and stored for 24 h in 4 degrees
      C cold HTK solution, followed by reperfusion with 37 degrees C Krebs-Henseleit
      buffer for 60 min. Liver enzymes in the effluent and bile flow were analyzed.
      Hepatocellular morphology was determined by histology and immunohistochemistry.
      RESULTS: Brain death reduced portal venous blood perfusion and bile flow, induced
      heme oxygenase-1 (HO-1), and resulted in hepatocellular damage. Isoflurane
      treatment did not prevent the reduction of portal venous blood perfusion or bile
      flow or the induction of HO-1. Accordingly, isoflurane was not capable of
      reducing the hepatocellular injury. CONCLUSIONS: Isoflurane does not protect from
      brain death-associated aggravation of cold hepatic ischemia-reperfusion injury.

PMID- 25598074
TI  - Prostate-specific membrane antigen-based imaging in prostate cancer: impact on
      clinical decision making process.
AB  - BACKGROUND: There is an ongoing need for an accurate imaging modality which can
      be used for staging purposes, metastatic evaluation, predicting biologic
      aggresiveness and investigating recurrent disease in prostate cancer. Prostate
      specific membrane antigen, given its favorable molecular characteristics, holds a
      promise as an ideal target for prostate cancer-specific nuclear imaging. In this
      study, we evaluated our initial results of PSMA based PET/CT imaging in prostate
      cancer. METHODS: A total of 22 patients with a median age and serum PSA level of
      68 years and 4.15 ng/ml, respectively underwent Ga-68 PSMA PET/CT in our hospital
      between Februrary and August 2014. Their charts were retrospectively reviewed in
      order to document the clinical characteristics, the indications for and the
      results of PSMA based imaging and the impact of Ga-68 PSMA PET/CT findings on
      disease management. RESULTS: The most common indications were rising PSA after
      local +/- adjuvant treatment followed by staging and metastatic evaluation before
      definitive or salvage treatment. All except 2 patients had prostatic +/-
      extraprostatic PSMA positive lesions. For those who had a positive result;
      treatment strategies were tailored accordingly. Above the PSA level of 2 ng/ml,
      none of the PSMA based nuclear imaging studies revealed negative results.
      CONCLUSIONS: PSMA based nuclear imaging has significantly impacted our way of
      handling patients with prostate cancer. Its preliminary performance in different
      clinical scenarios and ability to detect lesions even in low PSA values seems
      fairly promising and deserves to be supplemented with further clinical studies.

PMID- 25598076
TI  - Development of biomimetic tilapia collagen nanofibers for skin regeneration
      through inducing keratinocytes differentiation and collagen synthesis of dermal
      fibroblasts.
AB  - In this study, tilapia skin collagen sponge and electrospun nanofibers were
      developed for wound dressing. The collagen sponge was composed of at least two
      alpha-peptides, and its denaturation temperature was 44.99  degrees C. It did not
      change the number of spleen-derived lymphocytes in BALB/c mice, the ratio of
      CD4+/CD8+ lymphocytes, and the level of IgG or IgM in Sprague-Dawley rat. The
      contact angle, tensile strength, and weight loss temperature of collagen
      nanofibers were 21.2 degrees , 6.72+/-0.44 MPa, and 300  degrees C, respectively.
      The nanofibers could promote the viabilities of human keratinocytes (HaCaTs) and
      human dermal fibroblasts (HDFs), inducing epidermal differentiation through the
      gene expression of involucrin, filaggrin, and type I transglutaminase of HaCaTs,
      and they could also accelerate migration of HaCaTs with the expression of matrix
      metalloproteinase-9 and transforming growth factor-beta1 (TGF-beta1). Besides,
      the nanofibers could upregulate the protien level of Col-I in HDFs both via a
      direct effect and TGF-beta1 secreted from HaCaTs, thus facilitating the formation
      of collagen fibers. Furthermore, the collagen nanofibers stimulated the skin
      regeneration rapidly and effectively in vivo. These biological effects could be
      explained as the contributions from the biomimic extracellular cell matrix
      structure, hydrophilicity, and the multiple amino acids of the collagen
      nanofibers.

PMID- 25598077
TI  - "One-pot" synthesis of amidoxime via Pd-catalyzed cyanation and amidoximation.
AB  - A novel "one-pot" reaction was developed for the synthesis of aryl or heteroaryl
      substituted amidoxime compounds containing various functional groups.
      Fluorescence titration experiments coupled with theoretical analysis revealed
      that the steric hindrance and electronic effects of substituents influence the
      binding ability of the amidoxime compounds to uranyl ions. 

PMID- 25598075
TI  - Effects of echinochrome on ventricular repolarization in acute ischemia.
AB  - BACKGROUND: Myocardial ischemic electrophysiological alterations are associated
      with the generation of reactive oxygen species. However, electrophysiological
      effects of antioxidants are unclear. Our objective was to determine the effects
      of the antioxidant echinochrome on ventricular repolarization in a feline model
      of 30-min ischemia. METHODS AND RESULTS: Activation-recovery intervals were
      measured from 64 ventricular electrograms recorded before and during the LAD
      ligation in untreated animals (controls, n=5) and animals given echinochrome
      (1mg/kg, n=5 and 2mg/kg, n=7). In controls, ischemia resulted in the increase of
      repolarization dispersion, QTc and Tpeak-Tend intervals and precordial T wave
      amplitude dispersion. Echinochrome attenuated the ischemic increase of
      repolarization dispersion. The increased dose of echinochrome abolished the
      ischemic ECG repolarization changes but did not modify the incidence of
      ventricular arrhythmias. CONCLUSION: Echinochrome modified ischemic alterations
      of repolarization dispersion that were associated with the changes of the body
      surface T wave amplitude dispersion and Tpeak-Tend interval.

PMID- 25598078
TI  - Probing time-dependent mechanical behaviors of catch bonds based on two-state
      models.
AB  - With lifetime counter-intuitively being prolonged under forces, catch bonds can
      play critical roles in various sub-cellular processes. By adopting different
      "catching" strategies within the framework of two-state models, we construct two
      types of catch bonds that have a similar force-lifetime profile upon a constant
      force-clamp load. However, when a single catch bond of either type is subjected
      to varied forces, we find that they can behave very differently in both force
      history dependence and bond strength. We further find that a cluster of catch
      bonds of either type generally becomes unstable when subjected to a periodically
      oscillating force, which is consistent with experimental results. These results
      provide important insights into versatile time-dependent mechanical behaviors of
      catch bonds. We suggest that it is necessary to further differentiate those bonds
      that are all phenomenologically referred to as "Catch bonds". 

PMID- 25598079
TI  - Cell-based assay of MGAT2-driven diacylglycerol synthesis for profiling
      inhibitors: use of a stable isotope-labeled substrate and high-resolution LC/MS.
AB  - To demonstrate monoacylglycerol acyltransferase 2 (MGAT2)-mediated enzyme
      activity in a cellular context, cells of the murine secretin tumor cell-1 line of
      enteroendocrine origin were used to construct human MGAT2-expressing recombinant
      cell lines. Low throughput and utilization of radiolabeled substrate in a
      traditional TLC technique were circumvented by development of a high-resolution
      LC/MS platform. Monitoring incorporation of stable isotope-labeled D31-palmitate
      into diacylglycerol (DAG) allowed selective tracing of the cellular DAG synthesis
      activity. This assay format dramatically reduced background interference and
      increased the sensitivity and the signal window compared with the TLC method.
      Using this assay, several MGAT2 inhibitors from different chemotypes were
      characterized. The described cell-based assay adds a new methodology for the
      development and evaluation of MGAT2 inhibitors for the treatment of obesity and
      type 2 diabetes. 

PMID- 25598083
TI  - Medicaid expansions for the working age disabled: Revisiting the crowd-out of
      private health insurance.
AB  - Disabled individuals under 65 years old account for 15% of Medicaid recipients
      but half of all Medicaid spending. Despite their large cost, few studies have
      investigated the effects of Medicaid expansions for disabled individuals on
      insurance coverage and crowd-out of private insurance. Using an eligibility
      expansion that allowed states to provide Medicaid to disabled individuals with
      incomes less than 100% of the federal poverty level, I address these issues.
      Crowd-out estimates range from 49% using an ordinary least squares procedure to
      100% using two-stage least-squares analysis. This potentially large degree of
      crowd-out could have fiscal implications for the Affordable Care Act which has
      greatly expanded Medicaid eligibility in 2014. 

PMID- 25598081
TI  - A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to
      microvascular dysfunction during diabetic retinopathy via NADPH oxidase.
AB  - Retinal hyperpermeability and subsequent macular edema is a cardinal feature of
      early diabetic retinopathy (DR). Here, we investigated the role of bioactive
      lipid metabolites, in particular 12/15-lipoxygenase (LOX)-derived metabolites, in
      this process. LC/MS lipidomic screen of human retinal endothelial cells (HRECs)
      demonstrated that 15-HETE was the only significantly increased metabolite (2.4 +/
      0.4-fold, P = 0.0004) by high glucose (30 mM) treatment. In the presence of
      arachidonic acid, additional eicosanoids generated by 12/15-LOX, including 12-
      and 11-HETEs, were significantly increased. Fluorescein angiography and retinal
      albumin leakage showed a significant decrease in retinal hyperpermeability in
      streptozotocin-induced diabetic mice lacking 12/15-LOX compared with diabetic WT
      mice. Our previous studies demonstrated the potential role of NADPH oxidase in
      mediating the permeability effect of 12- and 15-HETEs, therefore we tested the
      impact of intraocular injection of 12-HETE in mice lacking the catalytic subunit
      of NADPH oxidase (NOX2). The permeability effect of 12-HETE was significantly
      reduced in NOX2(-/-) mice compared with the WT mice. In vitro experiments also
      showed that 15-HETE induced HREC migration and tube formation in a NOX-dependent
      manner. Taken together our data suggest that 12/15-LOX is implicated in DR via a
      NOX-dependent mechanism. 

PMID- 25598080
TI  - Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.
AB  - The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis,
      nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely
      diagnosis of these different stages, particularly NASH, is important for both
      potential reversibility and limitation of complications. Liver biopsy remains the
      clinical standard for definitive diagnosis. Diagnostic tools minimizing the need
      for invasive procedures or that add information to histologic data are important
      in novel management strategies for the growing epidemic of NAFLD. We describe an
      "omics" approach to detecting a reproducible signature of lipid metabolites,
      aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded
      study of patients with different stages of NAFLD that involves profiling liver
      biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel
      of 20 plasma metabolites that includes glycerophospholipids, sphingolipids,
      sterols, and various aqueous small molecular weight components involved in
      cellular metabolic pathways, can be used to differentiate between NASH and
      steatosis. This identification of differential biomolecular signatures has the
      potential to improve clinical diagnosis and facilitate therapeutic intervention
      of NAFLD. 

PMID- 25598082
TI  - Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (-)
      epicatechin in healthy volunteers.
AB  - (-)-Epicatechin ((-)-EPI), a naturally occurring flavanol, has emerged as a
      likely candidate for cocoa-based product reported reductions in cardiometabolic
      risk. The present study aimed to determine the safety, tolerability,
      pharmacokinetics and pharmacodynamics of purified (-)-EPI administered to healthy
      volunteers. In this phase I, open-label, two-part single- and multiple-dose
      study, subjects received either a single dose (n = 9) of 50, 100 or 200 mg or
      multiple doses (n = 8) of 50 mg daily (q.d.) or twice daily (b.i.d) for 5 days.
      Blood was collected at 0, 0.5, 1, 2, 4 and 6 h after (-)-EPI administration in
      the single and multiple dose groups (blood collection repeated in day 5). Samples
      were analyzed by HPLC-HR-ESI-MS for EPI and metabolite quantification. In the
      q.d. and b.i.d. groups, blood samples were analyzed for NO surrogates and
      follistatin levels as well as, platelet mitochondrial complexes I, V and citrate
      synthase activity levels. (-)-EPI was well tolerated and readily absorbed with
      further phase 2 metabolism. On day 5, in the q.d. and b.i.d. groups, there were
      significant increases in plasma nitrite of 30% and 17%, respectively. In the q.d.
      group on day 5 vs. day 1, platelet mitochondrial complexes I, IV and citrate
      synthase activities demonstrated a significant increase of ~92, 62 and 8%,
      respectively. Average day 5 follistatin AUC levels were ~2.5 fold higher vs. day
      1 AUC levels in the b.i.d. group. (-)-EPI was safe to use, with no observed
      adverse effects, and our findings suggest that increases in NO metabolites,
      mitochondrial enzyme function and plasma follistatin levels may underlie some of
      the beneficial effects of cocoa products or (-)-EPI as reported in other studies.

PMID- 25598085
TI  - The Journal of Pediatric Surgery-celebrates its 50th anniversary.

PMID- 25598086
TI  - Try again. Fail again. Fail better.

PMID- 25598084
TI  - Hepatocyte nuclear factor (HNF) 4alpha transactivation of cytochrome P450 (Cyp)
      2d40 promoter is enhanced during pregnancy in mice.
AB  - We have recently reported that transactivation of cytochrome P450 (CYP) 2D6
      promoter by hepatocyte nuclear factor (HNF) 4alpha is enhanced during pregnancy,
      and this is triggered in part by altered expression of small heterodimer partner
      (SHP) and Kruppel-like factor 9 (KLF9). The objective of this study is to
      determine whether this is conserved for mouse endogenous Cyp2d gene(s). Among the
      eight Cyp2d homologs of mouse we examined, only Cyp2d40 expression was found
      induced (by 6-fold) at term pregnancy as compared to pre-pregnancy level. In mice
      where hepatic Hnf4alpha was knocked-down, the pregnancy-mediated increase in
      Cyp2d40 expression was abrogated. Results from transient transfection, promoter
      reporter assays, and electrophoretic mobility shift assays indicated that
      HNF4alpha transactivates Cyp2d40 promoter via direct binding to -117/-105 of the
      gene. Chromatin immunoprecipitation assay showed a 2.3-fold increase in HNF4alpha
      recruitment to Cyp2d40 promoter during pregnancy. Results from mice treated with
      an SHP inducer (i.e., GW4064) and HepG2 cells co-transfected with KLF9 suggest
      that neither SHP nor KLF9 is involved in the increased HNF4alpha transactivation
      of Cyp2d40 promoter during pregnancy. Together, our results indicate that while
      the underlying molecular mechanism is different from that for CYP2D6, Cyp2d40 is
      induced during pregnancy through enhanced transactivation by HNF4alpha. 

PMID- 25598088
TI  - A pain in the NEC: research challenges and opportunities.
AB  - This lecture will describe how the properties of heparin-binding EFG-like growth
      factor (HB-EGF) can be utilized to protect the intestines from necrotizing
      enterocolitis (NEC), to augment the effects of stem cells in the treatment of
      NEC, and to improve the production of tissue-engineered intestine. It will also
      explore the role of the enteric nervous system in the development of NEC. 

PMID- 25598087
TI  - Standing on the shoulders of giants: a scientific journey from Singapore to stem
      cells.
AB  - Cellular therapy was introduced in the early 1980s as adoptive immunotherapy for
      cancer and has now expanded to stem cell treatment for a wide variety of
      indications. During the same period, the concept of the fetus as a patient
      evolved from fantasy to everyday reality. The intersection of these two fields
      offers great potential for cures in childhood diseases. The fetal treatment of
      spina bifida is one such disease. Global surgery has also emerged as a cost
      effective approach to reducing the worldwide burden of childhood disease. 

PMID- 25598089
TI  - Next step in minimally invasive surgery: hybrid image-guided surgery.
AB  - Surgery, interventional radiology, and advanced endoscopy have all developed
      minimally invasive techniques to effectively treat a variety of diseases with
      positive impact on patients' postoperative outcomes. However, those techniques
      are challenging and require extensive training. Robotics and computer sciences
      can help facilitate minimally invasive approaches. Furthermore, surgery, advanced
      endoscopy, and interventional radiology could converge towards a new hybrid
      specialty, hybrid image-guided minimally invasive therapies, in which the three
      fundamental disciplines could complement one another to maximize the positive
      effects and reduce the iatrogenic footprint on patients. The present manuscript
      describes the fundamental steps of this new paradigm shift in surgical therapies
      that, in our opinion, will be the next revolutionary step in minimally invasive
      approaches. 

PMID- 25598090
TI  - Understanding translational research: a play in four acts.
AB  - Translational research (TR) bridges discovery to clinical delivery. All TR also
      requires the development of an intervention. Classical 'bench to bedside' TR is
      responsible for many important advances, but cannot account for many others,
      which begin with clinical observations. My personal involvement in TR has ranged
      from exploration of long-term mechanical circulatory support devices to
      amelioration of the progression of Alzheimer's disease to the pharmacologic cure
      of smallpox. This experience suggests that most TR is opportunistic and
      inefficient. A strategic approach to TR based on a better understanding of the
      processes it entails could enhance progress in TR despite its increasing
      complexity. 

PMID- 25598091
TI  - An extracorporeal artificial placenta supports extremely premature lambs for 1
      week.
AB  - PURPOSE: The treatment of extreme prematurity remains an unsolved problem. We
      developed an artificial placenta (AP) based on extracorporeal life support (ECLS)
      that simulates the intrauterine environment and provides gas exchange without
      mechanical ventilation (MV) and compared it to the current standard of neonatal
      care. METHODS: Extremely premature lambs (110-120 days; term=145d) were used. AP
      lambs (n=9) were cannulated (jugular drainage, umbilical vein reinfusion) for
      ECLS. Control lambs (n=7) were intubated, ventilated, given surfactant, and
      transitioned to high-frequency oscillatory ventilation. All lambs received
      parenteral nutrition, antibiotics, and steroids. Hemodynamics, blood gases,
      hemoglobin, and circuit flows were measured. RESULTS: Four premature lambs
      survived for 1 week on the AP, with one surviving 6 days. Adequate oxygenation
      and ventilation were provided by the AP. The MV lambs survived 2-8 hours. Each of
      these lambs experienced a transient improvement with surfactant, but developed
      progressive hypercapnea and hypoxia despite high airway pressures and HFOV.
      CONCLUSIONS: Extremely premature lambs were supported for 1 week with the AP with
      hemodynamic stability and adequate gas exchange. Mechanically ventilated lambs
      succumbed within 8 hours. Further studies will assess control of fetal
      circulation and organ maturation on the AP.

PMID- 25598092
TI  - The many faces of hydrops.
AB  - PURPOSE: Fetal hydrops arises from multiple disease processes and can portend a
      grim prognosis. We reviewed our experience with hydropic fetuses to understand
      relevant antenatal anatomic and physiologic predictors of survival. METHODS: We
      reviewed fetal ultrasounds and echocardiograms of hydropic fetuses evaluated from
      1996 to 2013. RESULTS: Overall neonatal survival in 167 fetuses was 44% (range, 0
      75%) and was influenced by the underlying disease process. The anatomic
      distribution of fluid varied and was not significantly different between
      survivors and nonsurvivors. Univariate analysis indicated that resolution of
      hydrops and delivery at a later gestational age were predictive of survival (OR:
      5.7 (95% CI: 2.5-13.2) and OR: 1.3 (95% CI: 1.1-1.4), respectively). Fetal
      intervention also improved survival in some diseases. Echocardiograms were
      reviewed to group fetuses with similar cardiac physiology and defined categories
      with high or low/normal cardiothoracic ratio (CTR). Among patients with a high
      CTR, the cardiovascular profile score was predictive of survival (p=0.009).
      CONCLUSION: Survival in hydrops depends on the underlying disease, available
      fetal therapies to resolve hydrops, and the gestational age of delivery and not
      on the specific anatomic manifestations of hydrops. In hydropic fetuses with high
      CTRs, the cardiovascular profile score may be a useful prognostic indicator.

PMID- 25598093
TI  - Are all pulmonary hypoplasias the same? A comparison of pulmonary outcomes in
      neonates with congenital diaphragmatic hernia, omphalocele and congenital lung
      malformation.
AB  - INTRODUCTION: Patients with congenital diaphragmatic hernias (CDH), omphaloceles,
      and congenital lung malformations (CLM) may have pulmonary hypoplasia and
      experience respiratory insufficiency. We hypothesize that given equivalent lung
      volumes, the degree of respiratory insufficiency will be comparable regardless of
      the etiology. METHODS: Records of all fetuses with CDH, omphalocele, and CLM
      between January 2000 and June 2013 were reviewed. MRI-based observed-to-expected
      total fetal lung volumes (O/E-TFLV) were calculated. An analysis of outcomes in
      patients with O/E-TFLV between 40% and 60%, the most inclusive range, was
      performed. RESULTS: 285 patients were evaluated (161, CDH; 24, omphalocele; 100,
      CLM). Fetuses with CDH had the smallest mean O/E-TFLV. CDH patients were
      intubated for longer and had a higher incidence of pulmonary hypertension. Fifty
      six patients with the three diagnoses had an O/E-TFLV of 40%-60%. The need for
      ECMO, supplemental oxygen at 30days of life, and 6-month mortality were similar
      among groups. CDH patients had a significantly longer duration of intubation and
      higher incidence of pulmonary hypertension than the other two diagnoses.
      CONCLUSION: Given equivalent lung volumes (40%-60% of expected), CDH patients
      require more pulmonary support initially than omphalocele and CLM patients. In
      addition to lung volumes, disease-specific factors, such as pulmonary
      hypertension in CDH, also contribute to pulmonary morbidity and overall outcome.

PMID- 25598094
TI  - Enteral nutrition in neonatal and pediatric extracorporeal life support: a survey
      of current practice.
AB  - PURPOSE: The purpose of this study was to characterize enteral (EN) nutrition
      practices in neonatal and pediatric patients receiving extracorporeal life
      support (ECLS). METHODS: A Web-based survey was administered to program directors
      and coordinators of Extracorporeal Life Support Organization centers providing
      neonatal and pediatric ECLS. The survey assessed patient and clinical factors
      relating to the administration of EN. RESULTS: A total of 122 responses (122/521,
      23.4%) from 96 institutions (96/187; 51.3%) were received. One hundred fifteen
      provided neonatal or pediatric ECLS, and 84.2% reported utilizing EN during ECLS.
      55% and 71% of respondents provide EN 'often' or 'always' for venoarterial and
      venovenous ECLS, respectively. EN was reported as given 'often' or 'always' by
      24% with increased vasopressor support, 53% with "stable" vasopressor support,
      and 60% with weaning of vasopressor support. Favorable diagnosis for providing EN
      includes respiratory distress syndrome, pneumonia, asthma, trauma/post-operative,
      pulmonary hemorrhage, and infectious cardiomyopathy. Vasopressor requirement and
      underlying diagnosis were the primary or secondary determinant of whether to
      provide EN 81% and 72% of the time. 38% reported an established protocol for
      providing EN. CONCLUSION: EN support is common but not uniform among neonatal and
      pediatric patients receiving ECLS. ECLS mode, vasopressor status, and underlying
      diagnosis play an important role in the decision to provide EN.

PMID- 25598096
TI  - Partial or complete coverage of experimental spina bifida by simple intra
      amniotic injection of concentrated amniotic mesenchymal stem cells.
AB  - PURPOSE: We sought to determine whether simple intra-amniotic delivery of
      concentrated amniotic mesenchymal stem cells (afMSCs) may elicit prenatal
      coverage of experimental spina bifida. METHODS: Time-dated pregnant Sprague
      Dawley dams (n=24) exposed to retinoic acid for the induction of fetal neural
      tube defects were divided in three groups. Group I had no further manipulations.
      Groups II and III received volume-matched intra-amniotic injections of either
      saline (Group II) or a suspension of syngeneic afMSCs labeled with green
      fluorescent protein (Group III) in all fetuses (n=202) on gestational day 17
      (term=21-22 days). Animals were killed before term. Statistical comparisons were
      by ANOVA (P<0.05). RESULTS: Of 165 fetuses viable at euthanasia, a spina bifida
      was present in 58% (96/165), with no significant differences in defect dimension
      across the groups (P=0.19). However, variable degrees of coverage of the defect
      by a rudimentary skin confirmed histologically were only present in Group III
      (P<0.001), in which donor afMSCs were documented, with no differences between
      Groups I and II (P=0.98). CONCLUSIONS: Amniotic mesenchymal stem cells can induce
      partial or complete coverage of experimental spina bifida after concentrated
      intra-amniotic injection. Trans-amniotic stem cell therapy (TRASCET) may become a
      practical option in the prenatal management of spina bifida.

PMID- 25598095
TI  - Neonatal carotid repair at ECMO decannulation: patency rates and early neurologic
      outcomes.
AB  - PURPOSE: Neonates placed on veno-arterial extracorporeal membrane oxygenation (VA
      ECMO) undergo either carotid repair or ligation at decannulation. Study aims were
      to evaluate carotid patency rates after repair and to compare early neurologic
      outcomes between repaired and ligated patients. METHODS: A retrospective study of
      all neonates without congenital heart disease (CHD) who had VA-ECMO between 1989
      and 2012 was completed using our institutional ECMO Registry. Carotid patency
      after repair, neuroimaging studies, and auditory brainstem response (ABR) testing
      at time of discharge were examined. RESULTS: 140 neonates were placed on VA-ECMO
      during the study period. Among survivors, 84% of carotids repaired and imaged
      remained patent at last study. No significant differences were observed between
      infants in the repaired and ligated groups regarding diagnosis, ECMO duration, or
      length of stay. A large proportion (43%) developed a severe brain lesion after VA
      ECMO, but few failed their ABR testing. Differences in early neurologic outcomes
      between the two groups of survivors were not significant. CONCLUSIONS: At this
      single institution, carotid patency is excellent following repair at ECMO
      decannulation. No increased incidence of severe brain lesions or greater
      neurosensory impairment in the repair group was observed. Further studies are
      needed to investigate the effects of ligation on longer-term neurocognitive
      outcomes.

PMID- 25598098
TI  - Thoracoscopic placement of phrenic nerve pacers for diaphragm pacing in
      congenital central hypoventilation syndrome.
AB  - PURPOSE: Congenital central hypoventilation syndrome (CCHS), or Ondine's curse,
      is a rare disorder affecting central respiratory drive. Patients with this
      disorder fail to ventilate adequately and require lifelong ventilatory support.
      Diaphragm pacing is a form of ventilatory support which can improve mobility
      and/or remove the tracheostomy from CCHS patients. Little is known about
      complications and long-term outcomes of this procedure. METHODS: A single-center
      retrospective review was performed of CCHS patients undergoing placement of
      phrenic nerve electrodes for diaphragm pacing between 2000 and 2012. Data
      abstracted from the medical record included operation duration, ventilation
      method, number of trocars required, and postoperative and pacing outcomes.
      RESULTS: Charts of eighteen patients were reviewed. Mean surgical time was 3.3+/
      0.7 hours. In all cases except one, three trocars were utilized for each
      hemithorax, with no conversions to open procedures. Five patients (27.8%)
      experienced postoperative complications. The mean ICU stay was 4.3+/-0.5 days,
      and the mean hospital stay is 5.7+/-0.3days. Eleven patients (61.1%) achieved
      their daily goal pacing times within the follow-up period. CONCLUSIONS:
      Thoracoscopic placement of phrenic nerve electrodes for diaphragmatic pacing is a
      safe and effective treatment modality for CCHS. Observed complications were
      temporary, and the majority of patients were able to achieve pacing goals.

PMID- 25598097
TI  - Nutritional outcomes in survivors of congenital diaphragmatic hernia (CDH)
      factors associated with growth at one year.
AB  - BACKGROUND: Malnutrition is prevalent among congenital diaphragmatic hernia (CDH)
      survivors. We aimed to describe the nutritional status and factors that impact
      growth over the 12-months following discharge from the pediatric intensive care
      unit (PICU) in this cohort. METHODS: CDH survivors, who were discharged from the
      PICU from 2000 to 2010 with follow-up of at least 12months, were included.
      Nutritional intake, anthropometric, and clinical variables were recorded.
      Multivariable linear regression was used to determine factors associated with
      weight-for-age Z-scores (WAZ) at 12months. RESULTS: Data from 110 infants, 67%
      male, 50% patch repair, were analyzed. Median (IQR) WAZ for the cohort was -1.4 (
      2.4 to -0.3) at PICU discharge and -0.4 (-1.3 to 0.2) at 12-months. The
      percentage of infants with significant malnutrition (WAZ<-2) decreased from 26%
      to 8.5% (p<0.001). Patch repair (p=0.009), protein intake<2.3g/kg/day (p=0.014),
      and birth weight (BW)<2.5kg (p<0.001) were associated with lower WAZ at 12
      months. CONCLUSIONS: CDH survivors had a significantly improved nutritional
      status in the 12-months after PICU discharge. Patch repair, lower BW, and
      inadequate protein intake were significant predictors of lower WAZ at 12-months.
      A minimum protein intake in the PICU of 2.3g/kg/day was essential to ensure
      optimal growth in this cohort.

PMID- 25598099
TI  - Endobronchial occlusion with one-way endobronchial valves: a novel technique for
      persistent air leaks in children.
AB  - PURPOSE: In children, persistent air leaks can result from pulmonary infection or
      barotrauma. Management strategies include surgery, prolonged pleural drainage,
      ventilator manipulation, and extracorporeal membrane oxygenation (ECMO). We
      report the use of endobronchial valve placement as an effective minimally
      invasive intervention for persistent air leaks in children. METHODS: Children
      with refractory prolonged air leaks were evaluated by a multidisciplinary team
      (pediatric surgery, interventional pulmonology, pediatric intensive care, and
      thoracic surgery) for endobronchial valve placement. Flexible bronchoscopy was
      performed, and air leak location was isolated with balloon occlusion. Retrievable
      one-way endobronchial valves were placed. RESULTS: Four children (16 months to 16
      years) had prolonged air leaks following necrotizing pneumonia (2), lobectomy
      (1), and pneumatocele (1). Patients had 1-4 valves placed. Average time to air
      leak resolution was 12 days (range 0-39). Average duration to chest tube removal
      was 25 days (range 7-39). All four children had complete resolution of air leaks.
      All were discharged from the hospital. None required additional surgical
      interventions. CONCLUSION: Endobronchial valve placement for prolonged air leaks
      owing to a variety of etiologies was effective in these children for treating air
      leaks, and their use may result in resolution of fistulae and avoidance of the
      morbidity of pulmonary surgery.

PMID- 25598100
TI  - Early versus delayed surgical correction of malrotation in children with critical
      congenital heart disease.
AB  - PURPOSE: The purpose of this study was to compare outcomes between early and
      delayed surgical correction of malrotation in children with critical congenital
      heart disease (CHD). METHODS: Patients with CHD who underwent cardiac surgery by
      1 year of age and had malrotation diagnosed during their initial admission at 34
      hospitals contributing to the Pediatric Health Information System in 2004-2009
      were included. Ladd's procedures performed during the first admission were
      considered early correction, and those at a subsequent admission were considered
      delayed. Interhospital variability in the proportion of patients undergoing
      delayed correction was assessed, and outcomes were compared between the groups.
      RESULTS: Of the 324 patients identified, 85.2% underwent early correction.
      Significant variability existed in the proportion of patients undergoing delayed
      correction across hospitals (p<0.0001). Baseline characteristics, including
      severity of CHD, were similar between the groups. In the delayed group, 27% of
      patients underwent a Ladd's procedure during an urgent or emergent admission, but
      none had volvulus or underwent intestinal resection. Rates of mortality and
      readmission within 1 year of malrotation diagnosis were similar in both groups.
      Chart validation confirmed 100% accuracy of diagnosis and treatment group
      assignment. CONCLUSIONS: In patients with critical CHD, delayed operative
      intervention for malrotation without volvulus may be a reasonable alternative.

PMID- 25598101
TI  - Thymectomy for myasthenia gravis in children: a comparison of open and
      thoracoscopic approaches.
AB  - PURPOSE: Thymectomy is an accepted component of treatment for myasthenia gravis
      (MG), but optimal timing and surgical approach have not been determined. Though
      small series have reported the feasibility of thoracoscopic resection, some
      studies have suggested that minimally invasive methods are suboptimal compared to
      open sternotomy owing to incomplete clearance of thymic tissue. Here we report
      the largest series of thymectomies for pediatric myasthenia gravis in the
      literature to date. METHODS: A retrospective review of patients undergoing
      thymectomy for MG between 1990 and 2013 in a tertiary referral hospital was
      performed. Twelve patients who underwent thoracoscopic thymectomy were compared
      to 16 patients who underwent open thymectomy via median sternotomy. Postoperative
      outcomes were determined by electronic chart review in consultation with the
      treating pediatric neurologist. Disease severities were graded according to a
      modified Myasthenia Gravis Foundation of America (MGFA) Quantitative MG (QMG)
      score. RESULTS: Overall, thoracoscopic resections tended to be performed on
      patients with earlier and less severe disease than open surgeries. Inpatient
      length of stay was significantly shorter after thoracoscopic surgery (mean 1.8 vs
      8.0 days, p=0.045). The preoperative and postoperative MGFA QMG scores were
      equivalent between the two groups. Both groups experienced a decrease in disease
      severity (p<0.001) after median follow-up time of 23 months in the thoracoscopic
      group and 44 months in the open group. CONCLUSIONS: Minimally invasive thymectomy
      for MG in children has increased in popularity as surgeons and neurologists
      compare the risks and benefits of surgery against other therapies. This analysis
      suggests that thoracoscopic thymectomy is not inferior to median sternotomy in
      terms of disease control in this small series, and that the morbidity of the
      thoracoscopic approach appears sufficiently low to be considered for early stage
      disease. Low perioperative morbidity and shortened hospital course make
      thoracoscopic thymectomy an attractive option in centers with sufficient medical
      and surgical experience.

PMID- 25598102
TI  - Identifying strategies to decrease infectious complications of gastroschisis
      repair.
AB  - PURPOSE: We describe the infectious complications of gastroschisis in order to
      identify modifiable factors to decrease these complications. METHODS: Data from
      155 gastroschisis patients (2001-2013) were reviewed. Complicated gastroschisis
      (intestinal atresia, necrotic bowel, or perforation) were excluded, leaving 129
      patients for review. Patient demographics, surgical details, postoperative
      infections and complications, and length of stay were reviewed. We used CDC
      definitions of infectious complications. RESULTS: The average gestational age of
      patients was 35.97weeks. Silos were used in 46% of patients (n=59) for an average
      of 7.4days. Thirty-one patients (24%) acquired an infection within the first
      60days of life. Patients who developed an infection were born earlier in
      gestation (P=0.02), weighed less (P=0.01), required silos more often (P=0.01),
      and received a sutured repair (P=0.04). Length of stay of patients with an
      infection was longer than in patients without infection (P=0.01). CONCLUSIONS:
      Infectious complications following gastroschisis repair are common. Subsets of
      gastroschisis patients at increased risk of infection include patients with
      silos, preterm delivery, low birth weight, and sutured repair. Based on our
      findings, our recommendation would be to carry gastroschisis patients to term and
      advocate against the routine use of silos, reserving their use for those cases
      when primary closure is not possible.

PMID- 25598103
TI  - A risk-stratified comparison of fascial versus flap closure techniques on the
      early outcomes of infants with gastroschisis.
AB  - BACKGROUND: While fascial closure is traditionally used in gastroschisis (GS),
      flap closure (skin or umbilical cord) has gained popularity. We evaluated early
      outcomes and complications of the two techniques. METHODS: A national, population
      based gastroschisis data registry was analyzed from 2005 to 2011. We compared
      fascial to flap closures and stratified patients into low or high-risk groups
      using the Gastroschisis Prognostic Score (GPS), a validated marker of post-natal
      bowel injury. Demographic and outcome data, including length of stay,
      complications, and markers of resource utilization were analyzed using Fisher's
      exact and Student's t-tests for categorical and continuous variables,
      respectively (p<0.05 significant). RESULTS: The analyzed dataset included 436
      fascial closures (344 [78.8%] low-risk, 92 high-risk) and 129 flap closures (112
      [86.7%] low-risk, 17 high-risk; p=0.06). Demographics and birth weight did not
      differ between groups. In patients with low GPS, flap closure demonstrated
      significant decreases in resource utilization and failure of closure, without
      differences in complication rates. Analysis of high-risk patients revealed no
      statistically significant differences in outcome. CONCLUSION: Flap closure was
      not associated with an increase in patient morbidity and seemed suitable as a
      definitive closure method for gastroschisis patients irrespective of disease
      severity. Furthermore, flap closure reduced several markers of resource
      utilization in patients with low-risk disease.

PMID- 25598104
TI  - The Esophageal Anastomotic Stricture Index (EASI) for the management of
      esophageal atresia.
AB  - BACKGROUND: Anastomotic stricture is the most common complication following
      repair of esophageal atresia. An Esophageal Anastomotic Stricture Index (EASI)
      based on the postoperative esophagram may identify patients at high risk of
      stricture formation. METHODS: Digital images of early postoperative esophagrams
      of patients undergoing EA repair from 2005 to 2013 were assessed. Demographics
      and outcomes including dilations were prospectively collected. Upper (U-EASI) and
      lower (L-EASI) pouch ratios were generated using stricture diameter divided by
      maximal respective pouch diameter. Score performances were evaluated with area
      under the receiver operator curves (AUC) and the Fisher's exact test for single
      and multiple (>3) dilatations. Interrater agreement was evaluated using the
      intraclass correlation coefficient (ICC). RESULTS: Forty-five patients had
      esophagrams analyzed; 28 (62%) required dilatation and 19 received >3 (42%). U
      EASI and L-EASI ratios ranged from 0.17 to 0.70, with L-EASI outperforming the U
      EASI as follows: L-EASI AUC: 0.66 for a single dilatation, 0.65 for >3
      dilatations; U-EASI AUC: 0.56 for a single dilatation, 0.67 for >3 dilatations.
      All patients with an L-EASI ratio of <=0.30 (n=8) required multiple esophageal
      dilatations, p=0.0006. The interrater ICC was 0.87. CONCLUSION: The EASI is a
      simple, reproducible tool to predict the development and severity of anastomotic
      stricture after esophageal atresia repair and can direct postoperative
      surveillance.

PMID- 25598105
TI  - Minimal vs. maximal esophageal dissection and mobilization during laparoscopic
      fundoplication: long-term follow-up from a prospective, randomized trial.
AB  - PURPOSE: We have previously conducted a prospective randomized trial (PRT)
      comparing circumferential phrenoesophageal dissection and esophageal mobilization
      (MAX) to minimal dissection/mobilization (MIN). The MIN group had a decreased
      incidence of postoperative wrap herniation and need for reoperation. This study
      provides long-term follow-up of the patients from our center who participated in
      the PRT. METHODS: Parents of patients in the PRT were queried regarding symptoms,
      medication use, postoperative complications, and additional procedures. Medical
      records were reviewed. Student's t-test was used for continuous variables.
      Fisher's exact and chi-square with Yates correction were used where appropriate.
      RESULTS: Of patients from our center, 75.4% MAX and 72.5% MIN patients were
      contacted. Median time to follow-up was 6.5 years. A rise in the incidence of
      herniation was noted in both groups (22.7% to 36.5% MAX vs 2.8% to 12.2% MIN).
      Time to diagnosis of hernia was significantly longer in the MIN group (14.7+/-9.5
      months MAX vs 30.2+/-23.6 months MIN, P=0.04). There was no significant
      difference between MIN and MAX group in reflux symptoms or medication use.
      CONCLUSION: Long-term follow-up demonstrates an increase in incidence of
      herniation in both groups. Previously demonstrated higher risk of wrap herniation
      with maximal esophageal dissection during laparoscopic fundoplication remains
      supporting original findings.

PMID- 25598106
TI  - Laparoscopic vertical sleeve gastrectomy significantly improves short term weight
      loss as compared to laparoscopic adjustable gastric band placement in morbidly
      obese adolescent patients.
AB  - BACKGROUND: Bariatric surgery has shown to be an effective weight loss treatment
      in morbidly obese adolescents. We compared outcomes of laparoscopic adjustable
      gastric band (LAGB) to laparoscopic vertical sleeve gastrectomy (VSG). METHODS: A
      single institution, retrospective evaluation of a prospectively collected
      database of LAGB and VSG patients. RESULTS: 174 morbidly obese patients underwent
      bariatric surgery at our institution between 2006 and 2013. 137 patients
      underwent LAGB and 37 underwent VSG. There were no significant differences
      between LAGB vs. VSG groups on day of surgery for age, gender, ethnicity, weight,
      and BMI. At 24-month follow up, patients who underwent VSG vs. LAGB displayed
      significantly greater percent excess weight loss (70.9+/-20.7 vs. 35.5+/-28.6,
      P=0.004) and percent preoperative BMI loss (32.3+/-11.0 vs. 16.4+/-12.7,
      P=0.004). Both VSG and LAGB significantly improved levels of HDL, HgA1c, and
      fasting glucose. LAGB patients had more complications than VSG patients.
      CONCLUSION: Bariatric surgery is an effective treatment strategy in morbidly
      obese adolescents who have failed medical management. VSG results in greater
      short term weight and BMI loss when compared to LAGB. Longer follow up with more
      patients will be required to confirm the long term safety and efficacy of VSG in
      adolescent patients.

PMID- 25598107
TI  - Hirschsprung disease in the premature newborn: a population based study and 40
      year single center experience.
AB  - BACKGROUND/PURPOSE: Understanding of Hirschsprung disease (HD) in premature
      newborns (PHD) is anecdotal. We have sought in this study to identify the
      demographic and clinical features of PHD. METHODS: All patients with HD 1970-2011
      treated at our tertiary care children's hospital were identified. Patients with
      biopsy confirmed HD and EGA <37weeks were selected for further review. Prenatal
      and birth data, demographics, clinical signs, radiologic and pathologic data, and
      operative interventions were examined. The occurrence of PHD was observed using
      data from the Utah Department of Health database 1997-2011. RESULTS: 404 patients
      with HD from 1970 to 2011 were treated. Twenty-seven (6.7%) had PHD. Mean birth
      weight in PHD was 2196grams and mean gestational age 34 (range 29-36)weeks. Seven
      patients had Down syndrome. Nonchromosomal anomalies occurred in 25%. Median time
      from birth to biopsy diagnosis was 42days (range 2-316days). The most common
      presenting signs were abdominal distension and bilious emesis. The HD incidence
      in Utah for all births was 1/4322 (0.023%) and for premature infants 1/3885
      (0.027%). CONCLUSIONS: PHD are similar to term infants with HD. Diagnosis of HD
      is often delayed in premature newborns, and associated anomalies are more common.

PMID- 25598108
TI  - Operative indications in recurrent ileocolic intussusception.
AB  - BACKGROUND: Air-contrast enema (ACE) is standard treatment for primary ileocolic
      intussusception. Management of recurrences is less clear. This study aimed to
      delineate appropriate therapy by quantifying the relationship between recurrence
      and need for bowel resection, pathologic lead points (PLP), and complication
      rates. METHODS: After IRB approval, a single institution review of patients with
      ileocolic intussusception from 1997 to 2013 was performed, noting recurrences,
      outcomes, and complications. Fisher's exact and t-tests were used. RESULTS: Of
      716 intussusceptions, 666 were ileocecal. Forty-four underwent bowel resection,
      with 29 PLPs and 9 ischemia/perforation. Recurrence after ACE occurred in 96
      (14%). Recurrence did not predict PLP (P=0.25). Recurrence (>=3) was associated
      with higher resection rate (P=0.03), but not ischemia/perforation (P=0.75). ACE
      related complications occurred in 4 (0.5%) patients. Successful initial ACE had
      98% negative predictive value for resection and PLP (e.g., after successful ACE,
      2% had resections, 2% PLP). After failed initial ACE, 36% received resection, and
      23% had PLP (P<0.001). CONCLUSIONS: Recurrence is associated with a greater risk
      of resection but not PLP or ACE-complication. Failed ACE is associated with
      increased risk for harboring PLP and receiving resection. ACE should be the
      standard treatment in recurrent intussusception, regardless of number of
      recurrences.

PMID- 25598109
TI  - Enteral autonomy in pediatric short bowel syndrome: predictive factors one year
      after diagnosis.
AB  - PURPOSE: This study examined predictors of achieving enteral autonomy among
      pediatric short bowel syndrome (SBS) patients remaining on parenteral nutrition
      (PN) beyond one year. METHODS: A retrospective single-institution study of 171
      pediatric SBS patients (defined as >=50% small bowel (SB) loss or >=60 days of PN
      with onset before 6 weeks of age) was performed. Multivariate Cox proportional
      hazards analysis was conducted, with subgroup analysis of patients on PN for >=1
      year (n=59). Primary outcome was successful wean from PN. RESULTS: Over a follow
      up of 4.1+/-4.8 years, 64.3% of children weaned from PN. Mortality was 15.2%.
      Presence of >=10% expected SB length (hazard ratio [HR] 6.48, p=0.002) or an
      ileocecal valve (ICV; HR, 2.86, p<0.001) predicted PN weaning. Of those on PN >=1
      year, the wean rate was 50.8%, and ICV no longer predicted weaning (p=0.153).
      Predictors among those on PN >=1 year were: >=10% expected SB length (HR, 8.27,
      p=0.010), intestinal atresia (HR, 4.26, p=0.011), and necrotizing enterocolitis
      (NEC, HR, 2.84, p=0.025). CONCLUSIONS: SBS children on PN >=1 year continue to
      wean from PN, and those with >=10% of predicted SB length, NEC, or atresia are
      more likely to do so. These findings may help direct management and advice for
      these challenging patients.

PMID- 25598110
TI  - Metabolic bone disease in pediatric intestinal failure patients: prevalence and
      risk factors.
AB  - PURPOSE: Patients with intestinal failure (IF) are known to have impaired
      absorption of nutrients required for maintenance of skeletal mass. Rates and risk
      factors of low bone mineral density (BMD) are unknown in pediatric IF patients.
      METHODS: Following IRB approval, patients with IF having undergone DXA scans were
      identified and laboratory, clinical, and nutritional intake variables were
      recorded. Low BMD was defined by a z-score of less than or equal to -2.0.
      Univariate followed by multivariable regression analysis was performed. RESULTS:
      Sixty-five patients underwent a total of 99 routine DXA scans. Twenty-seven (41%)
      had vitamin D deficiency, 22 (34%) had low BMD, and nineteen (29%) had a history
      of fractures. Variables noted to be associated with low BMD (p<0.1) on univariate
      analysis were considered for multivariable regression. Multivariable regression
      identified WAZ and serum calcium levels (p<0.05) as independent predictors of low
      BMD z-score. None of the other evaluated factors were associated with the risk of
      low BMD. Low BMD was not associated with risk of fractures. CONCLUSION: There is
      a significant incidence of low BMD in children with IF. WAZ and lower serum
      calcium levels are associated with risk of low BMD. Additional long term
      prospective studies are needed to further characterize the risk factors
      associated with low BMD.

PMID- 25598111
TI  - The role of surgery for children with perianal Crohn's disease.
AB  - PURPOSE: Children with perianal Crohn's disease (PCD) are a unique and diverse
      patient population. The purpose of this study was to describe the spectrum of
      disease and role of surgery. METHODS: A retrospective chart review of all
      children having at least one surgical intervention for PCD over 10 years was
      performed. RESULTS: Fifty-seven patients (63% male) aged 0.5-17 (median 13) years
      were identified. Perianal disease consisted of skin tags (49%), superficial
      fistulae (49%), deep fistulae (37%), superficial abscesses (68%), deep abscesses
      (9%), skin breakdown (19%), and anal strictures (7%). 84% received anti-TNF
      therapy, with 27% treated with a second anti-TNF medication. Minor surgical
      procedures, commonly done during anti-TNF therapy, included abscess drainage
      (67%) and seton placement (33%). Major surgical procedures, done almost
      exclusively after anti-TNF failure, included defunctioning ileostomy (23%) and
      subtotal colectomy (9%). Follow-up ranged from 7 to 160 (median 54) months.
      CONCLUSIONS: Pediatric PCD has a wide range of disease severity. Minor surgery
      provides adequate drainage before and during anti-TNF therapy, while major
      surgery plays a role in medically refractory disease. Appropriate surgical
      intervention remains an important part of the treatment paradigm.

PMID- 25598112
TI  - Reducing computed tomography scans for appendicitis by introduction of a
      standardized and validated ultrasonography report template.
AB  - PURPOSE: Computed tomography (CT) for the diagnosis of appendicitis is associated
      with radiation exposure and increased cost. In an effort to reduce the diagnostic
      use of CT scans, we implemented a standardized ultrasound report template based
      on validated secondary signs of appendicitis. METHODS: In September 2012, as part
      of a quality improvement project, we developed and introduced a four category
      standardized ultrasound report template for limited right lower quadrant
      abdominal ultrasounds. Outcomes for patients undergoing ultrasound or CT scan for
      appendicitis between 9/10/2012 and 12/31/2013 (Period 2, n=2033) were compared to
      the three months prior to implementation (Period 1, n=304). RESULTS: In Period 1,
      78 of 304 (25.7%) patients had appendicitis versus 385 of 2033 (18.9%) in Period
      2 (p=0.006). Non-diagnostic exams decreased from 48% to 0.1% (p<0.001).
      Ultrasound sensitivity improved from 66.67% to 92.2% (p<0.001). Specificity did
      not significantly change (96.9% to 97.69%, p=0.46). CT utilization for
      appendicitis decreased from 44.3% in Period 1 to 14.5% at the end of Period 2
      (p<0.001). CONCLUSIONS: Implementation of a standardized ultrasound report
      template based on validated secondary signs of appendicitis nearly eliminated non
      diagnostic exams, improved diagnostic accuracy, and resulted in a striking
      decrease in CT utilization.

PMID- 25598113
TI  - A dynamic postoperative protocol provides efficient care for pediatric patients
      with non-ruptured appendicitis.
AB  - PURPOSE: Postoperative management of pediatric patients with non-ruptured
      appendicitis is highly variable and often includes an overnight stay in the
      hospital. We implemented a criteria-based postoperative protocol designed to
      eliminate postoperative antibiotics and facilitate timely discharge by utilizing
      the bedside nurse to evaluate for readiness for discharge. METHODS: We collected
      data on all patients with non-ruptured appendicitis at our institution following
      protocol implementation (May 1, 2012 to April 30, 2013) and compared them to a
      control group. RESULTS: 580 patients were treated for non-ruptured appendicitis
      (285 prior protocol, 295 new protocol). Following implementation of our protocol,
      there was an overall reduction in length of stay from 40.1 (SD 27.5) to 23.5 (SD
      20.8)h, and total cost of care per patient also decreased from $5783 (SD $2501)
      to $4499 (SD $1983) (p<0.001). There was no change in hospital readmission rate
      (1.1% prior protocol, 1.4% new protocol) or postoperative abscess rate (0.8%
      prior protocol, 0.3% new protocol). CONCLUSION: Our new protocol reveals the
      value of eliminating postoperative antibiotics and leveraging the continuous
      availability of the bedside nurse in the determination of readiness for
      discharge.

PMID- 25598114
TI  - Prognostic factors in fibrolamellar hepatocellular carcinoma in young people.
AB  - BACKGROUND/PURPOSE: Fibrolamellar hepatocellular carcinoma (FL-HCC) arises in
      pediatric/adolescent patients without cirrhosis. We retrospectively evaluated the
      impact of resection, nodal status, metastasis, and PRETEXT stage on overall
      survival (OS). METHODS: With IRB approval, we reviewed records of 25 consecutive
      pediatric patients with FL-HCC treated at our institution from 1981 to 2011. We
      evaluated associations between OS and PRETEXT stage, nodal involvement,
      metastasis, and complete resection. RESULTS: Median age at diagnosis was
      17.1years (range, 11.6-20.5). Median follow-up was 2.74years (range, 5-9.5). Five
      (28%) patients had PRETEXT stage 1 disease, 10 (56%) had stage 2, 2 (11%) had
      stage 3, and 2 (11%) had stage 4 disease. On presentation, 17 (68%) patients had
      N1 disease, and 7 (28%) had parenchymal metastases. Complete resection was
      achieved in 17 (80.9%) of 21 patients who underwent resection. Five-year OS was
      42.6%. Survival was positively associated with complete resection (P =0.003),
      negative regional lymph nodes (P =0.044), and lower PRETEXT stage (P <0.001),
      with a trend for metastatic disease (P =0.05). CONCLUSIONS: In young patients
      with FL-HCC, lower PRETEXT stage and complete resection correlated with prolonged
      survival, while metastatic disease and positive lymph node status were associated
      with poor prognosis. Thus, we recommend complete resection and regional
      lymphadenectomy whenever possible.

PMID- 25598115
TI  - Effect of concurrent metastatic disease on survival in children and adolescents
      undergoing lung resection for metastatic osteosarcoma.
AB  - PURPOSE: To evaluate the impact of treated extra-pulmonary metastatic disease on
      overall (OS) and event-free survival (EFS) for pediatric osteosarcoma patients
      undergoing pulmonary metastatectomy. METHODS: We retrospectively reviewed
      pediatric patients who were treated for osteosarcoma at our institution from 2001
      to 2011 and received pulmonary metastatectomy (n=76). We compared OS and EFS
      between patients with metastases limited to the lungs (Group A, n=58) to those
      with treated extra-pulmonary metastases (Group B, n=18) at the time of first
      pulmonary metastatectomy. RESULTS: The estimated median OS and EFS from first
      pulmonary metastatectomy were 2.0years (95% CI 1.5-2.8years) and 5.5months (95%
      CI 3.0-8.1months), respectively. Median OS was significantly greater for Group A
      (2.6years, 95% CI 1.9-3.8) compared to Group B (0.9years, 95% CI 0.6-1.5) (log
      rank p=0.0001). Median EFS was significantly greater for Group A (7.9months, 95%
      CI 5.0-10.7) compared to Group B (1.6months, 95% CI 0.8-2.7) (log rank p<0.0001).
      Independent predictors of OS included extra-pulmonary metastatic disease at the
      time of first thoracotomy, bilateral pulmonary metastases, and >4 nodules
      resected at first thoracotomy (all p<0.001). CONCLUSIONS: Osteosarcoma patients
      with treated extra-pulmonary metastatic disease at the time of pulmonary
      metastatectomy have significantly worse survival compared to those with disease
      limited to the lungs.

PMID- 25598117
TI  - Pediatric surgical complications of major genitourinary reconstruction in the
      exstrophy-epispadias complex.
AB  - PURPOSE: Urinary continence is the goal of exstrophy-epispadias complex (EEC)
      reconstruction. Patients may require a continent urinary diversion (CUD) if they
      are a poor candidate for bladder neck reconstruction or are receiving an
      augmentation cystoplasty (AC) or neobladder (NB). This study was designed to
      identify the incidence of surgical complications among various bowel segments
      typically used for CUD. METHODS: A prospectively kept database of 1078 patients
      with EEC at a tertiary referral center from 1980 to 2012 was reviewed for major
      genitourinary reconstruction. Patient demographics, surgical indications,
      perioperative complications, and outcomes were recorded. RESULTS: Among reviewed
      EEC patients, 134 underwent CUD (81 male, 53 female). Concomitant AC was
      performed in 106 patients and NB in 11. Median follow up time after initial
      diversion was 5 years. The most common CUD bowel segments were appendix and
      ileum. The most common surgical complications after CUD were small bowel
      obstruction, post-operative ileus, and intraabdominal abscess. There was a
      significantly increased risk in the occurrence of pelvic or abdominal abscess
      when colon was used as a conduit compared to all other bowel segments (OR=16.7,
      95% CI: 1.16-239) and following NB creation compared to AC (OR=39.4, 95% CI: 3.66
      423). At postoperative follow-up, 98% of patients were continent of urine via
      their stoma. CONCLUSION: We report the largest series to date examining CUD in
      the EEC population. The increased risk of abdominal and pelvic abscesses in
      patients who receive a colon CUD and undergo NB compared to AC indicates that
      while surgical complications following major genitourinary reconstruction are
      rare, they do occur. Practitioners must be wary of potential complications that
      are best managed by a multi-disciplinary team approach.

PMID- 25598116
TI  - Health disparities are important determinants of outcome for children with solid
      tumor malignancies.
AB  - PURPOSE: The purpose of this study was to identify health disparities in children
      with non-CNS solid tumor malignancies and examine their impact on disease
      presentation and outcome. METHODS: We examined the records of all children
      (age<=18years) diagnosed with a non-CNS solid tumor malignancy and enrolled in
      the Texas Cancer Registry between 1995 and 2009 (n=4603). The primary outcome
      measures were disease stage and overall survival (OS). Covariates included
      gender, age, race/ethnicity, year of diagnosis, socioeconomic status (SES), and
      driving distance to the nearest pediatric cancer treatment facility. Statistical
      analyses included life table methods, logistic, and Cox regression. Statistical
      significance was defined as p<0.05. RESULTS: Children with advanced-stage disease
      were more likely to be male, <10years old, and Hispanic or non-Hispanic Blacks
      (all p<0.05). Distance to treatment and SES did not impact stage of disease at
      presentation. However, Hispanic and non-Hispanic Blacks and patients in the
      lowest SES quartile had the worst 1- and 5-year survival (all p<0.05). The
      adjusted OS differed by age, race, and stage, but not SES or distance to the
      nearest treatment facility. CONCLUSIONS: Race/ethnicity plays an important role
      in survival for children with non-CNS solid tumor malignancies. Future work
      should better define these differences to establish mechanisms to decrease their
      impact.

PMID- 25598119
TI  - Pediatric emergency department thoracotomy: a large case series and systematic
      review.
AB  - BACKGROUND/PURPOSE: The emergency department thoracotomy (EDT) is rarely utilized
      in children, and is thus difficult to identify survival factors. We reviewed our
      experience and performed a systematic review of reports of EDT in pediatric
      patients. METHODS: Patients age <=18 years who received an EDT from 1991 to 2012
      at our institution and all published case series were reviewed. Data analyzed
      include age, sex, mechanism of injury (MOI), injury patterns, presence of vital
      signs (VS) or signs of life (SOL) in the field/ED, return of spontaneous
      circulation (ROSC), and survival. RESULTS: A total of 252 patients were analyzed.
      84% were male. 51% sustained penetrating injuries, and median age was 15 years.
      Upon arrival, 17% had VS, and 35% had SOL. After EDT, 30% experienced ROSC. The
      survival rate was 1.6% for blunt trauma, 10.2% for penetrating injuries, and 6.0%
      overall. CONCLUSION: Survival of pediatric patients following EDT is comparable
      to recent analyses in adults. Children who sustain blunt injury and are without
      SOL have been uniformly unsalvageable. Children who sustain penetrating trauma
      and have SOL or are without SOL for a short time prior to arrival have been
      salvageable. There are no reported EDT survivors less than 14 years of age
      following blunt injury.

PMID- 25598118
TI  - Does timing of neonatal inguinal hernia repair affect outcomes?
AB  - PURPOSE: The purpose of this study was to examine practice variability and
      compare outcomes between early and delayed neonatal inguinal hernia repair (IHR).
      METHODS: Patients admitted to neonatal intensive care units with a diagnosis of
      IH who underwent IHR by age 1 year in the Pediatric Health Information System
      from 1999 to 2011 were included. IHR after the index hospitalization was
      considered delayed. Inter-hospital variability in the proportion of delayed
      repairs and differences in outcomes for each group were compared. A propensity
      score matched analysis was performed to account for baseline differences between
      treatment groups. RESULTS: Of the 2030 patients identified, 32.9% underwent
      delayed IHR with significant variability in the proportion of patients having
      delayed repair across hospitals (p<0.0001). More patients in the delayed group
      had a congenital anomaly or received life supportive measures prior to IHR (all
      p<0.01), and 8.2% of patients undergoing delayed repair had a diagnosis of
      incarceration at repair. More patients in the early group underwent reoperation
      for hernia within 1 year (5.9% vs. 3.7%, p=0.02). Results were similar after
      performing a propensity score matched analysis. CONCLUSIONS: Significant
      variability in practice exists between children's hospitals in the timing of IHR,
      with delayed repair associated with incarceration and early repair with a higher
      rate of reoperation.

PMID- 25598121
TI  - Recent trends in the operative experience of junior pediatric surgical
      attendings: a study of APSA applicant case logs.
AB  - PURPOSE: Pediatric surgical education and workforce have changed significantly in
      the past decade. To document trends in the operative experiences of junior
      pediatric surgeons, we examined case logs submitted by applicants for membership
      to APSA. METHODS: Case logs for 164 APSA membership applicants from 2006 to 2013
      were reviewed. Total case volume, categories, and specific operations were
      analyzed. Negative binomial regression assessed for significant associations
      between the number of cases and the application year, presence of a pediatric
      surgery training program, region of the country, and years since fellowship
      completion. RESULTS: Overall case numbers decreased initially after 2006/2007,
      but have remained stable since. Decreasing trends were seen in a number of
      specific cases/categories. The number of newborn cases did not change.
      Significant variations in operative experience were identified depending upon
      region, presence of a pediatric surgery training program, and years since
      fellowship completion. Median reported value for several important cases was <=4
      per year, and for some was zero. CONCLUSION: These data describing the experience
      of young pediatric surgeons supplement recent observations regarding pediatric
      surgery fellows and general surgery residents. The limited exposure of surgeons
      to particularly rare conditions appears to be an unresolved problem. This
      information will be useful in developing future workforce proposals.

PMID- 25598120
TI  - Managing moderately injured pediatric patients without immediate surgeon
      presence: 10 years later.
AB  - PURPOSE: Beginning in 2003, the pediatric emergency medicine (PEM) physician
      replaced the surgeon as the team leader for all level II trauma resuscitations at
      a busy pediatric trauma center. The purpose was to review the outcomes 10 years
      after implementing this practice change. METHODS: Trauma registry data for all
      level II activations requiring admission were extracted for the 21 months (April
      1, 2001-December 31, 2002) prior to policy change (period 1, **n=627) and
      compared to the admitted patients from the 10 subsequent years (2003-2013; period
      2, n=2694). Data included demographics, length of stay (LOS), injury severity
      score (ISS), readmissions, complications, and mortality. RESULTS: Mean ISS scores
      for admitted patients during period 1 (8.5) were higher than during period 2
      (7.8). During period 1, 53.6% of patients underwent abdominal CT versus 41.8% in
      period 2 (p<.001), and the median ED LOS was 135 versus 191 minutes in period 2.
      From 2000 to 2003, 91% of patients seen as level II trauma alerts were admitted
      compared to 56.6% of patients in period 2 (p<0.001). There were no missed
      abdominal injuries identified, and readmission rate was low. CONCLUSIONS: We
      conclude that level II trauma resuscitations can be safely evaluated and managed
      without immediate surgeon presence. Although ED LOS increased, admission rate and
      CT scan usage decreased significantly without an increase in missed injuries.

PMID- 25598122
TI  - Prevention of infectious complications after elective colorectal surgery in
      children: an American Pediatric Surgical Association Outcomes and Clinical Trials
      Committee comprehensive review.
AB  - OBJECTIVE: This goal of this review was to examine the clinical evidence in
      support of commonly utilized measures intended to reduce complications following
      elective colorectal surgery. DATA SOURCE: Literature searches were performed to
      identify relevant studies from Medline, PubMed, and Cochrane databases. STUDY
      SELECTION: The American Pediatric Surgery Association Outcomes and Clinical
      Trials Committee selected eight questions to address this topic systematically in
      the context of three management areas: 1) appropriate utilization of systemic
      antibiotics for colorectal procedures, 2) reduction of stool burden through
      mechanical bowel preparation, and 3) intraluminal gut decontamination through use
      of enteral nonabsorbable antibiotics. Primary outcomes of interest included the
      occurrence of infectious and mechanical complications related to stool burden and
      intraluminal bacterial concentration (incisional surgical site infection,
      anastomotic leakage, and intraabdominal abscess). RESULTS: The evidence in
      support of each management category was systematically reviewed, graded, and
      summarized in the context of the review's primary outcomes. Practice
      recommendations were made as deemed appropriate by the committee. CONCLUSIONS:
      Clinical evidence in support of interventions to reduce infectious complications
      following colorectal surgery is derived almost exclusively from the adult
      literature. High-quality evidence to guide clinical practice in children is
      sorely needed, as the available data may have only limited relevance to pediatric
      colorectal diseases.

PMID- 25598123
TI  - Peroral endoscopic myotomy for treatment of achalasia in children and
      adolescents.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel endoscopic technique for
      treatment of achalasia (AC) and has shown exciting results in adults. However,
      little is known about the safety and efficacy of POEM in children and
      adolescents. Herein we report our preliminary results of POEM for children and
      adolescents with AC. METHODS: POEM was performed in 9 consecutive patients with
      AC, whose age ranged from 10 to 17years. After submucosal injection, a submucosal
      tunnel was created. Endoscopic myotomy of muscle bundles was then achieved under
      direct vision. The mucosal entry was closed by several clips. A validated
      clinical symptom score (Eckardt score), LES pressure, esophageal diameters and
      procedure-related complications were used to evaluate the outcomes. RESULTS: All
      9 patients underwent POEM successfully. Mean operation time was 56.7minutes. Mean
      myotomy length was 8.3cm. Among them, 4 patients underwent circular myotomy and 5
      underwent full-thickness myotomy. Symptoms remitted in all of the cases during a
      follow-up of 3-30months, Eckardt score was significantly reduced (preoperation vs
      postoperation, 7.0+/-1.9 vs 0.8+/-0.8, P<0.05). Mean LES pressure decreased from
      26.8mm Hg to 9.1mm Hg. Mean diameter of esophagus was dramatically decreased
      (preoperation vs postoperation, 50.6+/-4.9mm vs 29.6+/-3.7mm, P<0.05). No serious
      complications related to POEM were encountered. CONCLUSIONS: Our initial
      experience suggests that POEM is a safe and effective method for treatment of
      achalasia in children and adolescents. Further evaluation and long-term data are
      mandatory for a more confirmed conclusion.

PMID- 25598124
TI  - Long-term effects of fundoplication in children with chronic airway diseases.
AB  - BACKGROUND: Association between chronic airway diseases (CAD) and
      gastroesophageal reflux disease (GERD) is well described, but causality has not
      yet been conclusively established. This study evaluates the therapeutic
      significance of laparoscopic Thal fundoplication in children with CAD and
      diagnosed GERD. METHODS: We performed a retrospective analysis of 182
      neurologically nonimpaired children, all with medically refractory CAD and GERD
      undergoing laparoscopic Thal fundoplication. The clinical response, ability to
      wean oral and inhaled medication and satisfaction with postoperative results were
      evaluated. RESULTS: Main symptoms disappeared completely in 68.7% of patients and
      were markedly improved in a further 22% of patients following surgery. Complete
      discontinuation of medication was achieved in 70.1-96.4% of cases and reduced in
      a further 1.8-23.5%. One intraoperative complication occurred (gastric
      perforation), however no conversion to laparotomy was necessary. Postoperative
      Dumping Syndrome occurred in 1% of cases and was managed dietetically. Prolonged
      postoperative dysphagia occurred in 4.3% of patients, but disappeared within 8
      weeks in all but one case. CONCLUSIONS: Our study suggests that Thal
      fundoplication in neurologically nonimpaired children with CAD and documented
      GERD is effective and safe. Children unresponsive to preoperative medical
      management showed significant improvement in airway symptoms together with a
      marked reduction in the need for medication. We conclude that laparoscopic Thal
      fundoplication represents a significant treatment worthy of consideration in this
      group of patients.

PMID- 25598126
TI  - Gap measurement in patients with esophageal atresia: not a trivial matter.

PMID- 25598125
TI  - Arnold Salzberg, HB, MD: The Pied Piper of MCV.
AB  - Salzbergian?solz-berge-en? adjective of, relating to, or following the teachings
      of Arnold Salzberg. Noun one who embodies all that Arnold Salzberg taught about
      humanity. Noun one who has obtained his or her HB degree. Webster's dictionary
      would probably define "Salzbergian" as one who trained under Arnold Salzberg and
      exhibits the same great character traits, mentoring ability, and surgical skills.
      These might be the words that are used, but many times words cannot do justice to
      describing something so special. Arnold Salzberg was many things to many
      different people, "father figure," "wonderful advisor and resource," "ultimate
      mentor," "humanitarian," but when he was asked how he wanted to be remembered, he
      simply smiled and replied, "Icon...that would be nice." Never at a loss for words
      or humor and forever with an open door to his office, home, and heart, Dr.
      Salzberg embodied what so many medical students, residents, and attendings have
      been striving for, the ideal combination of physician and human being. 

PMID- 25598127
TI  - Reply to letter to the editor.

PMID- 25598128
TI  - Letter to the editor.

PMID- 25598129
TI  - Reply to letter to the editor.

PMID- 25598130
TI  - Highly selective colorimetric sensing of Hg(II) ions in aqueous medium and in the
      solid state via formation of a novel M-C bond.
AB  - For the first time an easy-to-make receptor 2-chloro-3-(thiazol-2
      ylamino)naphthalene-1,4-dione (R1) for highly selective sensing of Hg(ii) ions in
      aqueous solution and in the solid state through the formation of an Hg-C bond was
      developed. The Hg(ii) ion sensing properties of R1 were investigated using UV
      Vis, fluorescence and (1)H & (13)C NMR spectral studies. The results indicated
      that the receptor selectively senses Hg(ii) ions via the formation of a 1 : 1
      complex of moderate stability (Ka = 3.5 * 10(4) M(-1)). The NMR spectral studies
      indicated that complexation between R1 and Hg(ii) occurs through the formation of
      an Hg-C bond (after deprotonation), which was confirmed by a single crystal XRD
      analysis of the product. When Hg(ii) was added to a solution of R1 in DMF-water
      (1 : 9 v/v), a dramatic color change from pale brown to blue was observed, while
      many common cations and anions did not interfere with the recognition process.
      The detection limit was 0.3 MUM, which is much lower than the permissible limit
      of Hg(ii) in drinking water (0.001 mg L(-1)) as recommended by the WHO. The
      simple grinding of R1 with Hg(ii) in the solid state also exhibited the same
      dramatic colour change which is easily detectable visually. 

PMID- 25598131
TI  - Pillar[5]arene based supramolecular prodrug micelles with pH induced aggregate
      behavior for intracellular drug delivery.
AB  - A novel type of dual pH-responsive supramolecular prodrug micelles based on host
      guest interactions of water-soluble pillar[5]arene (WP5) and methyl viologen
      functioned doxorubicin (MV-DOX) was prepared. It was found that the prodrug
      micelles could be aggregated upon acidic condition, which led to enhanced
      accumulation and better therapy effect. 

PMID- 25598132
TI  - Revealing a double-inversion mechanism for the F-+CH3Cl SN2 reaction.
AB  - Stereo-specific reaction mechanisms play a fundamental role in chemistry. The
      back-side attack inversion and front-side attack retention pathways of the
      bimolecular nucleophilic substitution (SN2) reactions are the textbook examples
      for stereo-specific chemical processes. Here, we report an accurate global
      analytic potential energy surface (PES) for the F(-)+CH3Cl SN2 reaction, which
      describes both the back-side and front-side attack substitution pathways as well
      as the proton-abstraction channel. Moreover, reaction dynamics simulations on
      this surface reveal a novel double-inversion mechanism, in which an abstraction
      induced inversion via a FH...CH2Cl(-) transition state is followed by a second
      inversion via the usual [F...CH3...Cl](-) saddle point, thereby opening a lower
      energy reaction path for retention than the front-side attack. Quasi-classical
      trajectory computations for the F(-)+CH3Cl(nu1=0, 1) reactions show that the
      front-side attack is a fast direct, whereas the double inversion is a slow
      indirect process.

PMID- 25598133
TI  - Inflammation in cold complex regional pain syndrome.
AB  - BACKGROUND: In patients with complex regional pain syndrome (CRPS), the
      temperature of the affected side often differs from that of the contralateral
      side. In the acute phase, the affected side is usually warmer than the
      contralateral side, the so-called 'warm' CRPS. This thermal asymmetry can develop
      into a colder affected side, the so-called 'cold' CRPS. In contrast to cold CRPS,
      in warm CRPS, inflammation is generally assumed to be present. However, there are
      reports of cold CRPS patients, successfully treated with vasodilatation therapy,
      who subsequently displayed warm CRPS. It seems that inflammation could be
      'hidden' behind vasomotor disturbance. This study was designed to test this
      hypothesis. METHODS: A retrospective analysis was made of patients in our CRPS
      database. We defined three types of CRPS: cold CRPS, neither cold nor warm
      (intermediate) CRPS, and warm CRPS. Of these patients, the difference between the
      level of the pro-inflammatory cytokines interleukin (IL)-6 (Delta IL-6) and tumor
      necrosis factor (TNF)-alpha (Delta TNF-alpha) in the affected extremity and that
      in the contralateral extremity was determined. RESULTS: The bilateral difference
      of the level of these cytokines did not differ among patients with cold CRPS,
      intermediate CRPS, or those with warm CRPS. CONCLUSION: Inflammation may be
      involved in cold CRPS.

PMID- 25598135
TI  - Evaluation of a PCR targeting fimbrial subunit gene (fimA) for rapid and reliable
      detection of Enteroaggregative Escherichia coli recovered from human and animal
      diarrhoeal cases.
AB  - The present study describes the utility of a chromosomal associated fimbrial
      subunit gene (fimA) for screening 'typical' as well as 'atypical'
      Enteroaggregative Escherichia coli (EAEC) by PCR and its possible role as a
      promising molecular marker for rapid detection of 'typical' and 'atypical' EAEC
      pathotype. 

PMID- 25598134
TI  - Glycated Hemoglobin Level and Risk of Hip Fracture in Older People with Type 2
      Diabetes: A Competing Risk Analysis of Taiwan Diabetes Cohort Study.
AB  - Hip fracture, which is associated with substantial morbidity and long-term
      mortality, imposes a major burden on the healthcare system. Diabetes is a risk
      factor for osteoporosis, which is a crucial risk factor of hip fracture. However,
      epidemiological studies investigating the risk of hip fracture among patients
      with type 2 diabetes are limited. This study explored the association between
      hemoglobin A1c (HbA1c) and the risk of hip fracture in people with type 2
      diabetes aged 65 years and older. We conducted a retrospective cohort study of
      20,025 older patients with type 2 diabetes who participated in the National
      Diabetes Case Management Program in Taiwan. The HbA1c level at the baseline and
      hip fracture incidence over an average of 7.41 years of follow-up were analyzed
      (maximum and standard deviation were 10.9 and 2.42 years, respectively). A total
      of 1514 hip fracture cases were recorded. The incidence rates of hip fracture
      were 9.15, 8.02, 9.58, 10.61, 12.51, and 13.43 per 1000 person-years in patients
      with baseline HbA1c levels of < 6%, 6-7%, 7%-8%, 8%-9%, 9%-10%, and >= 10%,
      respectively. After multivariate adjustment, the risk of hip fracture increased
      among patients with HbA1c levels of 9%-10% and >= 10.0% compared with patients
      with HbA1c levels of 6-7% (hazard ratio, 1.24; 95% confidence interval, 1.02-1.49
      and 1.32; 1.09-1.58, respectively). Significant linear trends among various HbA1c
      levels were observed (P  < 0.05). Patients with type 2 diabetes whose HbA1c
      levels exceeded 9.0% exhibited an increased risk of hip fracture, confirming a
      linear relationship. Our study's findings demonstrated the importance of glycemic
      control for fracture prevention in older adults with type 2 diabetes.

PMID- 25598136
TI  - Ureteritis cystica.

PMID- 25598137
TI  - Radiation for prostate cancer: intensity modulated radiation therapy versus
      proton beam.

PMID- 25598138
TI  - Nephrogenic adenoma of the pediatric ureter.

PMID- 25598139
TI  - Exploring patient and public involvement in stroke research: a qualitative study.
AB  - PURPOSE: To explore the experiences of patients and carers involved in patient
      and public involvement (PPI) activities for stroke research. METHODS: Semi
      structured interviews conducted with stroke survivors and carers (n = 11) were
      analysed using thematic analysis. RESULTS: Four key themes emerged: impact of PPI
      on the individual and the research process, credibility and expertise, level of
      involvement and barriers and facilitators to PPI for stroke survivors and carers.
      The perceived benefits to the research process included: asking questions,
      keeping researchers grounded and directing the research agenda. All participants
      drew upon their experiential expertise in their PPI role, but some also drew upon
      their professional expertise to provide additional credibility. Stroke survivors
      and carers can be involved in PPI at different levels of involvement
      simultaneously and the majority of participants wanted to be more involved.
      Barriers to involvement included: location, transport and stroke survivors
      capacity to concentrate and comprehend complex information. Facilitators
      included: reimbursement for travel and time and professionals effort to
      facilitate involvement. CONCLUSIONS: PPI in stroke research benefits stroke
      survivors and carers and is perceived to benefit the research process. The
      barriers and facilitators should be considered by professionals intending to
      engage stroke survivors and carers collaboratively in research. IMPLICATIONS FOR
      REHABILITATION: This study has implications for PPI in stroke rehabilitation
      research, which could also be extrapolated to stroke rehabilitation service
      development and evaluation. Professionals facilitating PPI need to invest in
      developing supportive relationships in order to maintain ongoing involvement.
      Professionals need to be aware of how the varied consequences of stroke might
      impede participation and strategies to facilitate involvement for all who wish to
      be involved. For each rehabilitation issue being considered professionals need to
      decide: (1) how representative of the specific rehabilitation population the PPI
      members need to be, (2) whether experience alone is sufficient or whether
      additional professional skills are required and (3) whether training is likely to
      assist involvement or potentially reduce the lay representation.

PMID- 25598141
TI  - The FLOWERING LOCUS T/TERMINAL FLOWER 1 Gene Family: Functional Evolution and
      Molecular Mechanisms.
AB  - In plant development, the flowering transition and inflorescence architecture are
      modulated by two homologous proteins, FLOWERING LOCUS T (FT) and TERMINAL FLOWER
      1 (TFL1). The florigen FT promotes the transition to reproductive development and
      flowering, while TFL1 represses this transition. Despite their importance to
      plant adaptation and crop improvement and their extensive study by the plant
      community, the molecular mechanisms controlling the opposing actions of FT and
      TFL1 have remained mysterious. Recent studies in multiple species have unveiled
      diverse roles of the FT/TFL1 gene family in developmental processes other than
      flowering regulation. In addition, the striking evolution of FT homologs into
      flowering repressors has occurred independently in several species during the
      evolution of flowering plants. These reports indicate that the FT/TFL1 gene
      family is a major target of evolution in nature. Here, we comprehensively survey
      the conserved and diverse functions of the FT/TFL1 gene family throughout the
      plant kingdom, summarize new findings regarding the unique evolution of FT in
      multiple species, and highlight recent work elucidating the molecular mechanisms
      of these proteins. 

PMID- 25598142
TI  - Specific RNA recognition by designer pentatricopeptide repeat protein.

PMID- 25598140
TI  - A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic
      ischaemic brain injury in mice.
AB  - Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term
      infants and the devastating consequences range from cerebral palsy, epilepsy and
      neurological deficit to death. Cellular damage post insult occurs after a delay
      and is mediated by a secondary neural energy failure. AMP-activated protein
      kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or
      calcium dysregulation, hallmarks of the neuronal cell death observed after HIE.
      AMPK activation has been implicated in the models of adult ischaemic injury but,
      as yet, there have been no studies defining its role in neonatal asphyxia. Here,
      we find that in an in vivo model of neonatal hypoxia-ischaemic and in
      oxygen/glucose deprivation in neurons, there is pathological activation of the
      calcium/calmodulin-dependent protein kinase kinase beta (CaMKKbeta)-AMPKalpha1
      signalling pathway. Pharmacological inhibition of AMPK during the insult promotes
      neuronal survival but, conversely, inhibiting AMPK activity prior to the insult
      sensitizes neurons, exacerbating cell death. Our data have pathological relevance
      for neonatal HIE as prior sensitization such as exposure to bacterial infection
      (reported to reduce AMPK activity) produces a significant increase in injury. We
      show that in an in vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose
      deprivation in neurons, there is a pathological activation of the CaMKKbeta
      AMPKalpha1 signalling pathway. Inhibiting AMPK during OGD promotes neuronal
      survival; conversely, inhibiting AMPK prior to OGD exacerbates cell death. Our
      data have clinical relevance as prior sensitization (e.g. exposure to bacterial
      infection reducing AMPK activity) increases injury. AMPK, AMP-activated protein
      kinase; HI, hypoxia-ischaemia; OGD, oxygen-glucose deprivation. 

PMID- 25598143
TI  - SNARE-RNAi results in higher terpene emission from ectopically expressed
      caryophyllene synthase in Nicotiana benthamiana.
AB  - Plants produce numerous terpenes and much effort has been dedicated to the
      identification and characterization of the terpene biosynthetic genes. However,
      little is known about how terpenes are transported within the cell and from the
      cell into the apoplast. To investigate a putative role of vesicle fusion in this
      process, we used Agrobacterium tumefaciens-mediated transient coexpression in
      Nicotiana benthamiana of an MtVAMP721e-RNAi construct (Vi) with either a
      caryophyllene synthase or a linalool synthase, respectively. Headspace analysis
      of the leaves showed that caryophyllene or linalool emission increased about five
      fold when N. benthamiana VAMP72 function was blocked. RNA sequencing and protein
      ubiquitination analysis of the agroinfiltrated N. benthamiana leaf extracts
      suggested that increased terpene emissions may be attributed to proteasome
      malfunction based on three observations: leaves with TPS+Vi showed (1) a higher
      level of a DsRed marker protein, (2) a higher level of ubiquitinated proteins,
      and (3) coordinated induced expression of multiple proteasome genes, presumably
      caused by the lack of proteasome-mediated feedback regulation. However,
      caryophyllene or linalool did not inhibit proteasome-related protease activity in
      the in vitro assays. While the results are not conclusive for a role of vesicle
      fusion in terpene transport, they do show a strong interaction between inhibition
      of vesicle fusion and ectopic expression of certain terpenes. The results have
      potential applications in metabolic engineering. 

PMID- 25598144
TI  - Empowering nurses with evidence-based practice environments: surveying Magnet(r),
      Pathway to Excellence(r), and non-magnet facilities in one healthcare system.
AB  - BACKGROUND: Nurses have an essential role in implementing evidence-based
      practices (EBP) that contribute to high-quality outcomes. It remains unknown how
      healthcare facilities can increase nurse engagement in EBP. PURPOSE: To determine
      whether individual or organizational qualities could be identified that were
      related to registered nurses' (RNs') readiness for EBP as measured by their
      reported EBP barriers, ability, desire, and frequency of behaviors. METHODS: A
      descriptive cross-sectional survey was used in which a convenience sample of
      2,441 nurses within one United States healthcare system completed a modified
      version of the Information Literacy for Evidence-Based Nursing questionnaire.
      Descriptive statistics, t tests, one-way ANOVA, and regression modeling were used
      to analyze the data. RESULTS: RNs employed by facilities designated by the
      American Nurses Credentialing Center (ANCC) as Magnet(r) or Pathway to
      Excellence(r) reported significantly fewer barriers to EBP than those RNs
      employed by non designated facilities. RNs in Magnet organizations had higher
      desire for EBP than Pathway to Excellence or non designated facilities. RNs
      educated at the baccalaureate level or higher reported significantly fewer
      barriers to EBP than nurses with less education; they also had higher EBP
      ability, desire, and frequency of behaviors. A predictive model found higher EBP
      readiness scores among RNs who participated in research, had specialty
      certifications, and engaged in a clinical career development program. LINKING
      EVIDENCE TO ACTION: Education, research, and certification standards promoted by
      the Magnet program may provide a nursing workforce that is better prepared for
      EBP. Organizations should continue structural supports that increase professional
      development and research opportunities so nurses are empowered to practice at
      their full capacity.

PMID- 25598146
TI  - Esophageal versus surface recording of diaphragm compound muscle action
      potential.
AB  - INTRODUCTION: Repeated diaphragm compound muscle action potential (CMAP)
      recordings may help to understand the pathophysiology of respiratory muscle
      weakness. Neurally adjusted ventilator assist (NAVA) uses esophageal EMG
      electrodes to drive the ventilator. We evaluated the feasibility of CMAP
      recordings using these electrodes and established normal values. METHODS:
      Bilateral cervical phrenic nerve electrical stimulation was performed in 15
      healthy volunteers. CMAP recordings with esophageal NAVA electrodes were compared
      with surface electrode recordings during inspiratory and expiratory pause.
      RESULTS: Compared with surface recordings, esophageal CMAP amplitudes were higher
      with increased latencies. Differences between the 2 techniques were most
      prominent in inspiration. For both recording techniques, amplitudes were higher,
      and latencies were longer during inspiration. Latencies were also longer when
      measured on the left side. CONCLUSIONS: Diaphragm CMAPs can be measured using the
      commercially available esophageal NAVA probe. This may facilitate repeated
      diaphragm CMAP studies in mechanically ventilated patients.

PMID- 25598145
TI  - Diverse mechanisms for spliceosome-mediated 3' end processing of telomerase RNA.
AB  - The 3' end of Schizosaccharomyces pombe telomerase RNA (SpTER1) is generated by
      spliceosomal cleavage, a reaction that corresponds to the first step of splicing.
      The observation that the spliceosome functions in 3' end processing raised
      questions about the evolutionary origin and conservation of this mechanism. We
      now present data in support of spliceosomes generating 3' ends of telomerase RNAs
      in other fungi. Strikingly, the mechanistic basis for restricting spliceosomal
      splicing to the first transesterification reaction differs substantially among
      species. Unlike S. pombe, two other fission yeasts rely on hyperstabilization of
      the U6 snRNA-5' splice site interaction to impede the 2nd step of splicing. In
      contrast, a non-canonical 5' splice site blocks the second transesterification
      reaction in Aspergillus species. These results demonstrate a conserved role for
      spliceosomes functioning in 3' end processing. Divergent mechanisms of uncoupling
      the two steps of splicing argue for multiple origins of this pathway. 

PMID- 25598147
TI  - Impulse control disorders in Parkinson's disease: don't set your mind at rest by
      self-assessments.
AB  - BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) and related conditions
      in Parkinson's disease (PD) patients are frequent, disabling and sometimes
      devastating neuropsychiatric behaviors. Current knowledge on the prevalence of
      ICDs in PD is mainly based on assessments with questionnaires or patient
      interviews. This study was designed to evaluate the reliability of self-assessed
      ICDs and related conditions in PD by exploring the agreement between self
      assessment of ICDs and related conditions in PD patients on the one hand and the
      estimation of their caregivers on the other hand. METHODS: After a short
      validation study of a novel ICD screening questionnaire, a cross-sectional study
      in 150 PD patients was performed. All patients filled out the self-assessment
      version of a screening questionnaire for ICDs, and caregivers completed an
      adapted version (n = 64). RESULTS: When comparing self-assessments of PD patients
      and ratings by their caregivers, significant differences with regard to the
      estimated prevalence of hypersexuality (55% vs. 17%), dopamine dysregulation
      syndrome (31% vs. 3%) and punding (22% vs. 9%) were found. CONCLUSIONS: Patients
      underestimate the presence and severity of some ICDs and related conditions,
      which shows how important assessments with caregivers are. After all, ICDs are
      probably much more frequent in PD than previously reported.

PMID- 25598148
TI  - The different surrogate measures of adiposity in relation to semen quality and
      serum reproductive hormone levels among Estonian fertile men.
AB  - The objective of this study was to investigate the relations of basic semen
      parameters and reproductive hormones with different surrogate measures of
      adiposity: body mass index (BMI), body fat percentage (BF%), waist circumference
      (WC) and waist-to-height ratio (WHtR). Standard semen analysis was performed and
      serum levels of reproductive hormones were measured in 260 male partners of
      pregnant women at a university hospital andrology centres in Estonia. Quartile
      analysis revealed that all adiposity markers were negatively related to sex
      hormone-binding globulin and total testosterone levels. After adjustment for
      covariates a high BF%, WC and WHtR were negatively associated with total sperm
      count. The BF% was also negatively related to semen volume. These significant
      changes occurred from a BF% >= 23.4%, WC > 98 cm and WHtR > 0.54. Next to these
      changes the BMI was not related to sperm parameters. This study shows that semen
      quality is affected by central adiposity and confirms earlier findings that
      adiposity markedly changes serum sex hormone levels. Further studies are required
      to find out what is the best body composition marker showing most clearly the
      relationships between adiposity, semen characteristics and sex hormone levels.

PMID- 25598149
TI  - The association between the neutrophil-to-lymphocyte ratio and mortality in
      critical illness: an observational cohort study.
AB  - INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is a biological marker
      that has been shown to be associated with outcomes in patients with a number of
      different malignancies. The objective of this study was to assess the
      relationship between NLR and mortality in a population of adult critically ill
      patients. METHODS: We performed an observational cohort study of unselected
      intensive care unit (ICU) patients based on records in a large clinical database.
      We computed individual patient NLR and categorized patients by quartile of this
      ratio. The association of NLR quartiles and 28-day mortality was assessed using
      multivariable logistic regression. Secondary outcomes included mortality in the
      ICU, in-hospital mortality and 1-year mortality. An a priori subgroup analysis of
      patients with versus without sepsis was performed to assess any differences in
      the relationship between the NLR and outcomes in these cohorts. RESULTS: A total
      of 5,056 patients were included. Their 28-day mortality rate was 19%. The median
      age of the cohort was 65 years, and 47% were female. The median NLR for the
      entire cohort was 8.9 (interquartile range, 4.99 to 16.21). Following
      multivariable adjustments, there was a stepwise increase in mortality with
      increasing quartiles of NLR (first quartile: reference category; second quartile
      odds ratio (OR) = 1.32; 95% confidence interval (CI), 1.03 to 1.71; third
      quartile OR = 1.43; 95% CI, 1.12 to 1.83; 4th quartile OR = 1.71; 95% CI, 1.35 to
      2.16). A similar stepwise relationship was identified in the subgroup of patients
      who presented without sepsis. The NLR was not associated with 28-day mortality in
      patients with sepsis. Increasing quartile of NLR was statistically significantly
      associated with secondary outcome. CONCLUSION: The NLR is associated with
      outcomes in unselected critically ill patients. In patients with sepsis, there
      was no statistically significant relationship between NLR and mortality. Further
      investigation is required to increase understanding of the pathophysiology of
      this relationship and to validate these findings with data collected
      prospectively.

PMID- 25598150
TI  - The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2
      arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels.
AB  - BACKGROUND AND PURPOSE: Palmitoylethanolamide (PEA) is an endogenous congener of
      anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and
      at transient receptor potential vanilloid type-1 (TRPV1) channels. The other
      endocannabinoid, 2-arachidonoylglycerol (2-AG), was recently suggested to act as
      a TRPV1 channel agonist. We investigated if PEA enhanced levels of 2-AG in vitro
      or in vivo and 2-AG activity at TRPV1 channels. EXPERIMENTAL APPROACH: Endogenous
      lipid levels were measured by LC-MS in (i) human keratinocytes incubated with PEA
      (10-20 MUM, 40 min, 6 and 24 h, 37 degrees C); (ii) the blood of spontaneously
      Ascaris suum hypersensitive beagle dogs given a single oral dose of
      ultramicronized PEA (30 mg.kg(-1), 1, 2, 4 and 8 h from administration); (iii)
      the blood of healthy volunteers given a single oral dose of micronized PEA (300
      mg, 2, 4 and 6 h from administration). Effects of 2-AG at TRPV1 channels were
      assessed by measuring intracellular Ca(2+) in HEK-293 cells over-expressing human
      TRPV1 channels. KEY RESULTS: PEA elevated 2-AG levels in keratinocytes (~3-fold)
      and in human and canine plasma (~2 and ~20-fold respectively). 2-AG dose
      dependently raised intracellular Ca(2+) in HEK-293-TRPV1 cells in a TRPV1
      dependent manner and desensitized the cells to capsaicin. PEA only slightly
      enhanced 2-AG activation of TRPV1 channels, but significantly increased 2-AG
      induced TRPV1 desensitization to capsaicin (IC50 from 0.75 +/- 0.04 to 0.45 +/-
      0.02 MUM, with PEA 2 MUM). CONCLUSIONS AND IMPLICATIONS: These observations may
      explain why several effects of PEA are attenuated by cannabinoid receptor or
      TRPV1 channel antagonists. LINKED ARTICLES: This article is part of a themed
      section on Endocannabinoids. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.

PMID- 25598152
TI  - Potential pharmacological uses of chalcones: a patent review (from June 2011 -
      2014).
AB  - INTRODUCTION: Chalcones are one of the major classes of naturally occurring
      compounds. A large number of synthetic routes have been reported for the
      synthesis of chalcones, the most classical and general being the Claisen-Schmidt
      condensation. Chalcones and their derivatives have a huge importance in medicinal
      chemistry, displaying a wide range of important pharmacological activities. AREAS
      COVERED: The authors provide an overview of the recent scientific reports
      describing the obtention and study of new chalcones. The review emphasizes the
      rationale behind the natural sources, the discovery, the design, the synthesis,
      the biological activities and the study of structure-activity relationships of
      the new chalcone derivatives. The article is based on the literature published
      from June 2011 - 2014 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 extracts containing chalcones have been published in
      bibliographic sources, the potential of this scaffold could be deeply studied in
      many different areas in which almost nothing has been described. A lot of work
      should be done to reach the potency and safety requirements needed to develop new
      chemical entities as new drugs.

PMID- 25598151
TI  - Prenatal regression of the trophotaenial placenta in a viviparous fish, Xenotoca
      eiseni.
AB  - The trophotaenial placenta is a branching, ribbon-like structure that extends
      from the perianal region of the embryo in viviparous teleost fishes belonging to
      the family Goodeidae. It is a hindgut-derived pseudoplacenta, which contributes
      to absorbing maternal nutrients during the prenatal stage. The trophotaeniae are
      known to reduce at birth; however, no previous study has evaluated the removal
      mechanisms. We report here the analysis of the trophotaeniae using the goodeid
      fish species Xenotoca eiseni. The X. eiseni trophotaenia consists of an epidermal
      cell layer, mesenchyme, vasculature, and circulating erythrocytes. The
      trophotaeniae had preliminary regressed when the embryo was born.
      Immunohistochemistry indicated that caspase3-activated cells with fragmented
      nuclei are present in the regressed processes of the fry immediately after birth,
      but not in the vasculature and blood cells. This finding suggests that the
      trophotaenia is rapidly resorbed by apoptosis in the last phase of the pregnancy
      and that its circulatory pathway is maintained. Such prenatal regression of
      pseudoplacentae has not been reported in other viviparous vertebrates. On the
      other hand, similar apoptotic remodeling in the gut has been reported in
      amphibians, which is regulated by thyroid hormone. Thus, apoptotic regression of
      the trophotaeniae might occur in a manner similar to amphibian metamorphosis. 

PMID- 25598154
TI  - Identification of Dck1 and Lmo1 as upstream regulators of the small GTPase Rho5
      in Saccharomyces cerevisiae.
AB  - The exact function and regulation of the small GTPase Rho5, a putative homolog of
      mammalian Rac1, in the yeast Saccharomyces cerevisiae have not yet been
      elucidated. In a genetic screen initially designed to identify novel regulators
      of cell wall integrity signaling, we identified the homologs of mammalian DOCK1
      (Dck1) and ELMO (Lmo1) as upstream components which regulate Rho5. Deletion
      mutants in any of the encoding genes (DCK1, LMO1, RHO5) showed hyper-resistance
      to cell wall stress agents, demonstrating a function in cell wall integrity
      signaling. Live-cell fluorescence microscopy showed that Dck1, Lmo1 and Rho5
      quickly relocate to mitochondria under oxidative stress and cell viability assays
      indicate a role of Dck1/Lmo1/Rho5 signaling in triggering cell death as a
      response to hydrogen peroxide treatment. A regulatory role in autophagy/mitophagy
      is suggested by the colocalization of Rho5 with autophagic markers and the
      decreased mitochondrial turnover observed in dck1, lmo1 and rho5 deletion
      mutants. Rho5 activation may thus serve as a central hub for the integration of
      different signaling pathways. 

PMID- 25598153
TI  - Successful treatment of kaposiform lymphangiomatosis with sirolimus.
AB  - Generalized lymphatic anomaly (GLA) is a rare and often fatal congenital
      lymphatic disorder that also commonly affects bone. Kaposiform lymphangiomatosis
      (KLA) is a novel subtype of GLA with poor prognosis and no proper treatment
      guidelines. A 9-year-old male with recurrent pleural effusion was clinically
      diagnosed as KLA. Following sirolimus therapy at a dose of 0.8 mg/m(2) twice
      daily, pleural effusion was significantly decreased and the general status of the
      patient markedly improved. The clinical course indicates that sirolimus may
      present an effective therapeutic option in KLA. Moreover, KLA should be
      considered in differential diagnosis for cases of GLA with coagulopathy.

PMID- 25598155
TI  - Mass and energy balances of sludge processing in reference and upgraded
      wastewater treatment plants.
AB  - This paper describes the preliminary assessment of a platform of innovative
      upgrading solutions aimed at improving sludge management and resource recovery in
      wastewater treatment plants. The effectiveness of the upgrading solutions and the
      impacts of their integration in model reference plants have been evaluated by
      means of mass and energy balances on the whole treatment plant. Attention has
      been also paid to the fate of nitrogen and phosphorus in sludge processing and to
      their recycle back to the water line. Most of the upgrading options resulted in
      reduced production of dewatered sludge, which decreased from 45 to 56 g SS/(PE *
      day) in reference plants to 14-49 g SS/(PE * day) in the upgraded ones, with
      reduction up to 79% when wet oxidation was applied to the whole sludge
      production. The innovative upgrades generally entail an increased demand of
      electric energy from the grid, but energy recovery from biogas allowed to
      minimize the net energy consumption below 10 kWh/(PE * year) in the two most
      efficient solutions. In all other cases the net energy consumption was in the
      range of -11% and +28% of the reference scenarios.

PMID- 25598156
TI  - A comprehensive review on utilization of wastewater from coffee processing.
AB  - The coffee processing industry is one of the major agro-based industries
      contributing significantly in international and national growth. Coffee fruits
      are processed by two methods, wet and dry process. In wet processing, coffee
      fruits generate enormous quantities of high strength wastewater requiring
      systematic treatment prior to disposal. Different method approach is used to
      treat the wastewater. Many researchers have attempted to assess the efficiency of
      batch aeration as posttreatment of coffee processing wastewater from an upflow
      anaerobic hybrid reactor (UAHR)-continuous and intermittent aeration system.
      However, wet coffee processing requires a high degree of processing know-how and
      produces large amounts of effluents which have the potential to damage the
      environment. Characteristics of wastewater from coffee processing has a
      biological oxygen demand (BOD) of up to 20,000 mg/l and a chemical oxygen demand
      (COD) of up to 50,000 mg/l as well as the acidity of pH below 4. In this review
      paper, various methods are discussed to treat coffee processing wastewaters; the
      constitution of wastewater is presented and the technical solutions for
      wastewater treatment are discussed.

PMID- 25598157
TI  - Lichen communities along a pollution gradient 40 years after decommissioning of a
      Cu-Ni smelter.
AB  - Pollution control initiatives in Greater Sudbury, Ontario, Canada, resulted in
      the decommissioning of the Coniston Smelter in 1972. The last assessment of the
      effects from the smelter on the surrounding lichen biota was in 1990, which
      showed an overall improvement in richness following these initiatives, but still
      few species were present close to the smelter. We examined five sites along this
      gradient to determine if this pattern is still present on the landscape. Sixty
      four macrolichen species in 15 genera were found. Lichen richness and Shannon
      diversity increased at all sites, but the increase was no longer linear with
      distance from the smelter. There was no significant difference between lichen
      richness and diversity at sites at increasing distances from the smelter. We show
      that past air pollution from the Coniston Smelter is no longer restricting lichen
      growth and development in the Greater Sudbury area as it was historically. Lichen
      populations are, therefore, now shaped by other environmental variables. 

PMID- 25598158
TI  - Distribution and health risk assessment of mercury in urban street dust from coal
      energy dominant Huainan City, China.
AB  - High levels of mercury contamination in urban street dust pose a great threat to
      human health. In this study, representative urban street dust samples in
      different urban zones were collected from industrial Huainan City, Eastern China.
      The distribution and human health risk of Hg in urban street dusts were
      investigated. In comparison with the soil background Hg values of Huainan and
      China, the average Hg concentration (0.16 +/- 0.14 mg kg(-1), n = 50) was
      significantly elevated, with a variation ranging from 0.02 to 0.56 mg kg(-1).
      Among the seven different urban zones, the industrial district had the highest
      levels of Hg, potentially deriving predominantly from the dust emissions of the
      nearby Pingwei coal-fired power plant. In addition, Hg concentrations in dust
      samples appear to increase with the decrease of particle size. The result of
      health risk assessment on Hg in these urban street dusts indicated that there was
      no significant risk of carcinogenesis for the adults living in Huainan city.

PMID- 25598160
TI  - Copper-catalyzed cyanomethylation of allylic alcohols with concomitant 1,2-aryl
      migration: efficient synthesis of functionalized ketones containing an alpha
      quaternary center.
AB  - A copper-catalyzed alkylation of allylic alcohols by alkyl nitriles with
      concomitant 1,2-aryl migration was developed. Formation of the alkyl nitrile
      radical was followed by its intermolecular addition to alkenes and the migration
      of a vicinal aryl group with the concomitant generation of a carbonyl
      functionality to complete the domino sequence. Mechanistic studies suggested that
      1,2-aryl migration proceeded through a radical pathway (neophyl rearrangement).
      The protocol provided an efficient route to functionalized ketones containing an
      alpha-quaternary center. 

PMID- 25598162
TI  - An unusual presentation of a rare pancreatic tumour in an atypical population.

PMID- 25598159
TI  - Air pollution and unintentional injury deaths in South Korea.
AB  - This study aimed to assess the association between exposure to air pollution and
      unintentional injury deaths in South Korea. Data regarding all unintentional
      injury deaths (17,566) in seven metropolitan cities from 2002 to 2008 were
      collected. Using a time-stratified case-crossover study, conditional logistic
      regression and subgroup analyses were performed after stratification by age,
      gender, and season. To evaluate immediate and delayed effects of air pollutants,
      we used both single lag and distributed lag models. The risk was expressed as an
      odds ratio (OR) per one interquartile range (IQR) of each air pollutant. During
      the study period, the median (IQR) levels of air pollutants were 0.005 (0.004
      0.007) ppm for sulfur dioxide (SO2), 0.02 (0.02-0.03) ppm for nitrogen dioxide
      (NO2), 0.03 (0.02-0.04) ppm for ozone (O3), 48.3 (34.9-67.0) MUg/m(3) for
      particulate matter <=10 MUm in aerodynamic diameter (PM10), and 0.36 (0.1-0.6)
      ppm for carbon monoxide (CO). All air pollutants, with the exception of PM10 and
      O3, were significantly associated with an increased risk of unintentional injury
      deaths; the maximum risk was observed in the distributed lag 1 model for SO2 (OR,
      1.119; 95% confidence interval, 1.022-1.226), NO2 (1.208; 1.043-1.400), and CO
      (1.012; 1.000-1.024). After stratification of the subjects by age, SO2, NO2, and
      CO were significantly associated with increased risk of unintentional injury
      deaths among subjects aged 60 years or older in the distributed lag 1 model,
      while O3 and PM10 were associated with increased risk among subjects aged 40 to
      59 years. However, in subjects younger than 40 years of age, we found no
      significant associations for any of the air pollutants. Our study suggested
      evidence for a short-term association between air pollutants and unintentional
      injury deaths, even at low pollutants levels.

PMID- 25598163
TI  - Electron migration behavior of Au/Cu multilayer films on Si substrates under UV
      radiation.
AB  - Au/Cu multilayer films were plated by the magnetron sputtering method on p
      Si(100) substrates. The sample temperature was changed from room temperature to
      44  degrees C under UV radiation in a vacuum within 120 minutes, and then
      remained stable with treatment time increased. Meanwhile, the surface roughness
      was changed from 4.2 nm to 5.9 nm and then also remained stable. But the
      interface width of Au/Cu still continued to increase during that steady stage.
      The calculation results show that the concentration gradient of Cu atoms fell to
      2.24 in 360 minutes from 3.45 at the beginning. The increase of defects in the
      grain boundaries of the Au layer was induced by UV radiation, because the Cu
      element had a smaller work function relative to the Au element and it was more
      likely to migrate to the surface layer through the grain boundaries of the Au
      layer. 

PMID- 25598161
TI  - Velocity-strengthening friction significantly affects interfacial dynamics,
      strength and dissipation.
AB  - Frictional interfaces abound in natural and man-made systems, yet their dynamics
      are not well-understood. Recent extensive experimental data have revealed that
      velocity-strengthening friction, where the steady-state frictional resistance
      increases with sliding velocity over some range, is a generic feature of such
      interfaces. This physical behavior has very recently been linked to slow stick
      slip motion. Here we elucidate the importance of velocity-strengthening friction
      by theoretically studying three variants of a realistic friction model, all
      featuring identical logarithmic velocity-weakening friction at small sliding
      velocities, but differ in their higher velocity behaviors. By quantifying energy
      partition (e.g. radiation and dissipation), the selection of interfacial rupture
      fronts and rupture arrest, we show that the presence or absence of strengthening
      significantly affects the global interfacial resistance and the energy release
      during frictional instabilities. Furthermore, we show that different forms of
      strengthening may result in events of similar magnitude, yet with dramatically
      different dissipation and radiation rates. This happens because the events are
      mediated by rupture fronts with vastly different propagation velocities, where
      stronger velocity-strengthening friction promotes slower rupture. These
      theoretical results may have significant implications on our understanding of
      frictional dynamics. 

PMID- 25598166
TI  - Enhanced photoreversible color switching of redox dyes catalyzed by barium-doped
      TiO2 nanocrystals.
AB  - Colloidal barium-doped TiO2 nanocrystals have been developed that enable the
      highly reversible light-responsive color switching of redox dyes with excellent
      cycling performance and high switching rates. Oxygen vacancies resulting from the
      Ba doping serve as effective sacrificial electron donors (SEDs) to scavenge the
      holes photogenerated in TiO2 nanocrystals under UV irradiation and subsequently
      promote the reduction of methylene blue to its colorless leuco form. Effective
      color switching can therefore be realized without relying on external SEDs, thus
      greatly increasing the number of switching cycles. Ba doping can also accelerate
      the recoloration under visible-light irradiation by shifting the absorption edge
      of TiO2 nanocrystals to a shorter wavelength. Such a system can be further casted
      into a solid film to produce a rewritable paper on which letters and patters can
      be repeatedly printed using UV light and then erased by heating; this process can
      be repeated for many cycles and does not require additional inks. 

PMID- 25598169
TI  - Annual dormancy cycles in buried seeds of shrub species: germination ecology of
      Sideritis serrata (Labiatae).
AB  - The germination ecology of Sideritis serrata was investigated in order to improve
      ex-situ propagation techniques and management of their habitat. Specifically, we
      analysed: (i) influence of temperature, light conditions and seed age on
      germination patterns; (ii) phenology of germination; (iii) germinative response
      of buried seeds to seasonal temperature changes; (iv) temperature requirements
      for induction and breaking of secondary dormancy; (v) ability to form persistent
      soil seed banks; and (vi) seed bank dynamics. Freshly matured seeds showed
      conditional physiological dormancy, germinating at low and cool temperatures but
      not at high ones (28/14 and 32/18  degrees C). Germination ability increased with
      time of dry storage, suggesting the existence of non-deep physiological dormancy.
      Under unheated shade-house conditions, germination was concentrated in the first
      autumn. S. serrata seeds buried and exposed to natural seasonal temperature
      variations in the shade-house, exhibited an annual conditional dormancy/non
      dormancy cycle, coming out of conditional dormancy in summer and re-entering it
      in winter. Non-dormant seeds were clearly induced into dormancy when stratified
      at 5 or 15/4  degrees C for 8 weeks. Dormant seeds, stratified at 28/14 or 32/18 
      degrees C for 16 weeks, became non-dormant if they were subsequently incubated
      over a temperature range from 15/4 to 32/18  degrees C. S. serrata is able to
      form small persistent soil seed banks. The maximum seed life span in the soil was
      4 years, decreasing with burial depth. This is the second report of an annual
      conditional dormancy/non-dormancy cycle in seeds of shrub species.

PMID- 25598168
TI  - Randomized trial of exercise and an online recovery tool to improve
      rehabilitation outcomes of cancer survivors.
AB  - PURPOSE: The purpose of this study was to test the effects of a cancer survivor
      exercise program and an online recovery awareness program (Restwise) on physical
      outcomes of aerobic capacity and muscle strength. DESIGN: Randomized controlled
      trial design. SETTING: Treasure Valley Family YMCA, Boise, ID. SAMPLE: Fifty
      cancer survivors. METHODS: Subjects were randomly assigned to the 12-week
      exercise program or the exercise program and Restwise. Restwise required users to
      complete daily objective and subjective ratings. Restwise compiles these data to
      provide individualized feedback recommending the exercise dose to maximize
      recovery and minimize fatigue. MAIN RESEARCH VARIABLE: Baseline and posttest
      measures of physical performance (6-minute walk, 1-repetition maximum of lower
      and upper body strength). FINDINGS: The exercise plus Restwise group demonstrated
      significant improvements (P < 0.001) that were found on all 3 physical
      measurements of strength and endurance. The exercise-only group demonstrated
      significant within-group improvement only on the 6-minute walk. The exercise plus
      Restwise group demonstrated an 18.5% greater improvement in the 6-minute walk,
      and a 35.2% and 45%, respectively, greater improvement on the leg and chest press
      than the exercise-only group. However, the between-group differences were not
      significant. CONCLUSION: Cancer survivors who use the Restwise online recovery
      program in conjunction with an exercise program demonstrated minimal clinically
      important differences compared with other clinical populations on all 3 measures,
      whereas the exercise-only group had improvements only on the 6-minute walk.
      Patient adherence to the Restwise program was good, and patients provided
      positive feedback.

PMID- 25598170
TI  - Cardiac sympathetic afferent reflex and its implications for sympathetic
      activation in chronic heart failure and hypertension.
AB  - Persistent excessive sympathetic activation greatly contributes to the
      pathogenesis of chronic heart failure (CHF) and hypertension. Cardiac sympathetic
      afferent reflex (CSAR) is a sympathoexcitatory reflex with positive feedback
      characteristics. Humoral factors such as bradykinin, adenosine and reactive
      oxygen species produced in myocardium due to myocardial ischaemia stimulate
      cardiac sympathetic afferents and thereby reflexly increase sympathetic activity
      and blood pressure. The CSAR is enhanced in myocardial ischaemia, CHF and
      hypertension. The enhanced CSAR at least partially contributes to the sympathetic
      activation and pathogenesis of these diseases. Nucleus of the solitary tract
      (NTS), hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral
      medulla are the most important central sites involved in the modulation and
      integration of the CSAR. Angiotensin II, AT1 receptors and NAD(P)H oxidase
      derived superoxide anions pathway in the PVN are mainly responsible for the
      enhanced CSAR in CHF and hypertension. Central angiotensin-(1-7), nitric oxide,
      endothelin, intermedin, hydrogen peroxide and several other signal molecules are
      involved in regulating CSAR. Blockade of the CSAR shows beneficial effects in CHF
      and hypertension. This review focuses on the anatomical and physiological basis
      of the CSAR, the interaction of CSAR with baroreflex and chemoreflex, and the
      role of enhanced CSAR in the pathogenesis of CHF and hypertension. 

PMID- 25598172
TI  - Evaluation of internal consistency of the epidermolysis bullosa oropharyngeal
      severity score (EBOS).
AB  - OBJECTIVE: To evaluate the internal consistency of the epidermolysis bullosa
      oropharyngeal severity score (EBOS). MATERIALS AND METHODS: Data from 92 patients
      of varying EB types/sub-types already described in a previous multi-center study
      were re-analyzed via the coefficient Cronbach's alpha (CR-alpha). Additionally,
      the corrected item total correlation between each item and the items' overall
      score with Pearson's product-moment correlation (rho) was calculated. RESULTS:
      The alpha coefficient for the mean total score of 17 items is 0.941. The inter
      observer reliability for disease severity score was excellent for oral medicine
      specialist (alpha = 0.924) and dermatologist (alpha = 0.916) and the intra
      observer reliability was good at Time 1 (alpha = 0.895) and Time 2 (alpha =
      0.897). The analysis of CR-alpha per single item revealed that alpha was greater
      than 0.904 for disease activity and 0.743 for structural damage, after the
      elimination of four items for oral medicine specialist and greater than 0.898 for
      disease activity and 0.769 for structural damage after the elimination of five
      items for dermatologist. Similarly the analysis of the corrected items-EBOS
      correlation showed that the same items do not correlate very well (rho < 0.4)
      with the overall EBOS. CONCLUSIONS: The EBOS turned out to have a strong and
      reliable internal consistency, as the majority of the EBOS' items were consistent
      with each other.

PMID- 25598173
TI  - Glucose oxidase and glucose for redox-initiating the free radical
      copolymerization of N-(ferrocenoylmethyl)acrylamide in aqueous cyclodextrin
      solution.
AB  - The glucose oxidase and glucose mediated formation of amphipilic copolymers of N
      (ferrocenoylmethyl)acrylamide (NFMA) and N,N-diethylacrylamide (DEA) in aqueous
      cyclodextrin solution is presented. Thereby, NFMA is not only a comonomer but
      also part of the redox initiation system. The obtained copolymers contain NFMA
      units between 1 and 10 mol%. The molecular masses of the copolymers are dependent
      on the ferrocene content, whereupon molecular weights between 38,000 and 71,000 g
      mol(-1) are achieved.

PMID- 25598174
TI  - Is vitamin D deficiency alone sufficient to increase the incidence of neonatal
      sepsis?

PMID- 25598175
TI  - Is obesity associated with advanced stage or grade of colon cancer?
AB  - Population-based studies from Europe have suggested that obesity is associated
      with more advanced stage colorectal cancer on presentation. Obesity is an even
      more prevalent issue in North America, but comparable data on associations with
      cancer are lacking. We reviewed the cases of 672 patients with colon cancer
      diagnosed between 2004 and 2008 in the province of Manitoba who underwent
      surgical resection at a Winnipeg Regional Health Authority-affiliated hospital.
      We tested if obesity was associated with more advanced cancer stage or grade. On
      multivariate analysis, after adjusting for age, sex,tumour location and
      socioeconomic status, we were unable to show any significant associations between
      body mass index of 30 or more and advanced stage or grade cancer on presentation.
      The reasons for the lack of association are likely multifactorial, including the
      pathophysiology of the disease and process factors, such as screening habits and
      colonoscopic diagnostic success rates in obese patients.

PMID- 25598171
TI  - Prolonged hypogonadism in males following withdrawal from anabolic-androgenic
      steroids: an under-recognized problem.
AB  - AIMS: To assess the frequency and severity of hypogonadal symptoms in male long
      term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use.
      DESIGN: Cross-sectional, naturalistic. SETTING: Out-patient facility.
      PARTICIPANTS: Twenty-four male former long-term AAS users and 36 non-AAS-using
      weightlifters, recruited by advertisement in Massachusetts, USA. Five of the
      former users were currently receiving treatment with physiological testosterone
      replacement, leaving 19 untreated users for the numerical comparisons below.
      MEASUREMENTS: The Structured Clinical Interview for DSM-IV, questions regarding
      history of AAS use, physical examination, serum hormone determinations and the
      International Index of Erectile Function (IIEF). FINDINGS: Compared with the 36
      non-AAS-using weightlifters, the 19 untreated former AAS users displayed
      significantly smaller testicular volumes [estimated difference, 95% confidence
      interval (CI) = 2.3 (0.1, 4.5) ml; P = 0.042] and lower serum testosterone levels
      [estimated difference: 95% CI = 131 (25, 227) dl; P = 0.009], with five users
      showing testosterone levels below 200 ng/dl despite abstinence from AAS for 3-26
      months. Untreated former users also displayed significantly lower scores on the
      IIEF sexual desire subscale [estimated difference: 95% CI = 2.4 (1.3, 3.4) points
      on a 10-point scale; P < 0.001]. In the overall group of 24 treated plus
      untreated former users, seven (29%) had experienced major depressive episodes
      during AAS withdrawal; four of these had not experienced major depressive
      episodes at any other time. Two men (8%) had failed to regain normal libidinal or
      erectile function despite adequate replacement testosterone treatment.
      CONCLUSIONS: Among long-term anabolic-androgenic steroid misusers, anabolic
      androgenic steroid-withdrawal hypogonadism appears to be common, frequently
      prolonged and associated with substantial morbidity.

PMID- 25598176
TI  - Outcomes of infection following pediatric spinal fusion.
AB  - BACKGROUND: Removal of instrumentation is often recommended as part of treatment
      for spinal infections, but studies have reported eradication of infection even
      with instrumentation retention by using serial debridements and adjuvant
      antibiotic pharmacotherapy. We sought to determine the effect of instrumentation
      retention or removal on outcomes in children with spinal infections. METHODS: We
      retrospectively reviewed the cases of patients who experienced early (< 3 mo) or
      late (>= 3 mo) infected spinal fusions. Patients were evaluated at least 2 years
      after eradication of the infection using the following protocol outcomes: follow
      up Cobb angle, curve progression and nonunion rates. RESULTS: Our sample included
      35 patients. The mean age at surgery was 15.1 +/- 6.0 years, 65.7% were girls,
      and mean follow-up was 41.7 +/- 26.9 months. The mean Cobb angle was 63.6 degrees
      +/- 14.5 degrees  preoperatively, 29.4 degrees  +/- 16.5 degrees  immediately
      after surgery and 37.2 degrees  +/- 19.6 degrees  at follow-up. Patients in the
      implant removal group (n = 21) were more likely than those in the implant
      retention group (n = 14) to have a lower ASA score (71.4% v. 28.6%, p = 0.03),
      fewer comorbidities (66.7% v. 21.4%, p = 0.03), late infections (81.0% v. 14.3%,
      p = 0.01) and deep infections (95.2% v. 64.3%, p = 0.03). Implants were retained
      in 12 of 16 (75.0%) patients with early infections and 2 of 19 (10.5%) with late
      infections. Patients with implant removal had a higher pseudarthrosis rate (38.1%
      v. 0%, p = 0.02) and a faster curve progression rate (5.8 +/- 9.8 degrees  per
      year v. 0.2 +/- 4.7 degrees  per year, p = 0.04). CONCLUSION: Implant retention
      should be considered, irrespective of the timing or depth of the infection.

PMID- 25598177
TI  - Supply versus demand: a review of application trends to Canadian surgical
      training programs.
AB  - Despite increases in medical school enrolment, applications to surgical residency
      programs in Canada have been in decline over the past decade, with an increasing
      number of unmatched surgical residency positions. We examined the current status
      of surgical residency in Canada and analyzed application trends (2002-2013) for
      surgical training programs across Canada. Our findings suggest that most
      undergraduate medical schools across Canada are having difficulty fostering
      interest in surgical careers. We propose that a lack of adequate early exposure
      to the surgical specialties during undergraduate training is a critical factor.
      Moving forward, we must examine how the best-performing institutions and surgical
      programs have maintained interest in pursuing surgical careers and adapt our
      recruitment methods to both maintain and grow future interest. As Mary Engelbreit
      said, "If you don't like something, change it; if you can't change it, change the
      way you think about it."

PMID- 25598179
TI  - Amnesia in modern surgery: revisiting Wangensteen's landmark studies of small
      bowel obstruction.
AB  - Before the publications of Owen Wangensteen and his colleagues in the early
      1930s, bowel obstruction was almost always fatal, and its treatment was
      ineffectual.Patients rarely survived surgical attempts to relieve the
      obstruction.Although other investigators were active in the field, the
      understanding of the pathophysiology of obstruction belongs almost entirely to
      Wangensteen. In this commentary, we review Wangensteen's landmark studies of
      small bowel obstruction and how they shaped the treatment of this condition.

PMID- 25598178
TI  - Does more than a single chest tube for mediastinal drainage affect outcomes after
      cardiac surgery?
AB  - BACKGROUND: The use of 1 or more mediastinal chest tubes has traditionally been
      routine for all cardiac surgery procedures to deal with bleeding. However, it
      remains unproven whether multiple chest tubes offer a benefit over a single chest
      tube. METHODS: All consecutive patients undergoing cardiac surgery (2005-2010)
      received at least 1 chest tube at the time of surgery based on surgeon
      preference. Patients were grouped into those receiving a single chest tube (SCT)
      and those receiving multiple chest tubes (MCT). The primary outcome was return to
      the operating room for bleeding or tamponade. RESULTS: A total of 5698
      consecutive patients were assigned to 2 groups: 3045 to the SCT and 2653 to the
      MCT group. Patients in the SCT group were older, more often female and less
      likely to undergo isolated coronary artery bypass graft than those in the MCT
      group. Unadjusted outcomes for SCT and MCT, respectively, were return to the
      operating room for bleeding or tamponade (4.7% v. 5.0%; p = 0.50), intensive care
      unit stay longer than 48 hours (25.5% v. 27.9%; p = 0.041, postoperative stay > 9
      days (31.5% v. 33.1%; p = 0.20) and mortality (3.8% v. 4.6%; p = 0.16). Logistic
      regression analysis, adjusted for clinical differences between groups, showed
      that the number of chest tubes was not associated with return to the operating
      room for bleeding or tamponade. CONCLUSION: The use of multiple mediastinal chest
      tubes after cardiac surgery confers no advantage over a single chest tube in
      preventing return to the operating room for bleeding or tamponade.

PMID- 25598180
TI  - The integration of minimally invasive surgery in surgical practice in a Canadian
      setting: results from 2 consecutive province-wide practice surveys of general
      surgeons over a 5-year period.
AB  - BACKGROUND: Although minimally invasive surgery (MIS) has been quickly embraced,
      the introduction of advanced procedures appears more complex. We assessed the
      evolution of MIS in the province of Quebec over a 5-year period to identify areas
      for improvement in the modern surgical era. METHODS: We developed, test-piloted
      and conducted a self-administered questionnaire among Quebec general surgeons in
      2007 and 2012 to examine stated MIS practice, MIS training and barriers and
      facilitators to the use of MIS. RESULTS: Response rates were 51.3% (251 of 489)
      in 2007 and 31.3% (153 of 491) in 2012. A significant increase was observed for
      performance of most advanced MIS procedures, especially for colectomy for benign
      (66.0% v. 84.3%, p < 0,001) and malignant diseases (43.3% v. 77.8%, p < 0,001)
      and for rectal surgery for malignancy (21.0% v. 54.6%, p < 0.001). More surgeons
      practised 3 or more advanced MIS procedures in 2012 than in 2007 (82.3% v. 64.3%,
      p < 0,001). At multivariate analysis, the 2007 survey administration was
      associated with fewer surgeons practising advanced MIS (odds ratio 0.13, 95%
      confidence interval 0.06-0.29). In 2012, more respondents stated they gained
      their skills during residency (p = 0.028). CONCLUSION: From 2007 to 2012 there
      was a significant increase in advanced MIS procedures practised by general
      surgeons in Quebec. This technique appears well established in current surgical
      practice. The growing place of MIS in residency training seems to be a paramount
      part of this development. Results from this study could be used as a baseline for
      studies focusing on ways to further improve the MIS practice.

PMID- 25598181
TI  - An ultra high performance liquid chromatography with tandem mass spectrometry
      method for plasma and cerebrospinal fluid pharmacokinetics of rhein in patients
      with traumatic brain injury after administration of rhubarb decoction.
AB  - Damage of blood-brain barrier is a common result of traumatic brain injury. This
      damage can open the blood-brain barrier and allow drug passage. An
      ultraperformance liquid chromatography with tandem mass spectrometry method was
      established to determine the concentration of rhein in the biofluids (plasma and
      cerebrospinal fluid) of patients with a compromised blood-brain barrier following
      traumatic brain injury after rhubarb administration. Furthermore, the
      pharmacokinetic profiles were analyzed. A triple-quadruple tandem mass
      spectrometer with electrospray ionization was used for rhein detection. The mass
      transition followed was m/z 283.06->239.0. The calibration curve was linear in
      the concentration range of 10-8000 ng/mL for the biofluids. The intra- and
      interday precisions were less than 10%. The relative standard deviation of
      recovery was less than 15% in biological matrices. The pharmacokinetic data
      showed that rhein was rapidly transported into biofluids, and exhibited a peak
      concentration 1 h after rhubarb administration. The elimination rate of rhein was
      slow. The AUCcerebrospinal fluid /AUCplasma (AUC is area under curve) of rhein
      was approximately 17%, indicating that portions of rhein could pass the impaired
      blood-brain barrier. The method was successfully applied to quantify rhein in the
      biofluids of all patients. The data presented can help to guide clinical
      applications of rhubarb for treating traumatic brain injury. 

PMID- 25598182
TI  - Plasma cholinesterase activity of rats, western grey kangaroos, alpacas, sheep,
      cattle, and horses.
AB  - INTRODUCTION: Plasma cholinesterase activity levels of various species may be of
      interest to toxicologists or pathologists working with chemicals that interfere
      with the activity of plasma cholinesterase. METHODS: We used a pH titration
      method to measure the plasma cholinesterase activity of six mammalian species.
      RESULTS: Plasma cholinesterase activity varied up to 50-fold between species:
      sheep (88 +/- 45 nM acetylcholine degraded per ml of test plasma per minute),
      cattle (94 +/- 35), western grey kangaroos (126 +/- 92), alpaca (364 +/- 70),
      rats (390 +/- 118) and horses (4539 +/- 721). DISCUSSION: We present a simple,
      effective technique for the assay of plasma cholinesterase activity levels from a
      range of species. Although labour-intensive, it requires only basic laboratory
      equipment.

PMID- 25598183
TI  - Heart failure in sub-Saharan Africa: review of the aetiology of heart failure and
      the role of point-of-care biomarker diagnostics.
AB  - Within Africa, the burden of heart failure is significant. This arises from the
      increase in cardiovascular disease and associated risk factors such as
      hypertension and diabetes, as well as causes of heart failure which are
      particular to sub-Saharan Africa, such as endomyocardial fibrosis. The lack of
      access to echocardiography and other imaging modalities, from a cost and
      technical perspective, combined with the predominantly rural nature of many
      countries with poor transport links, means that the vast majority of people never
      obtain an appropriate diagnosis. Similarly, research has been limited on the
      causes and treatment of heart failure in Africa and in particular endemic causes
      such as EMF and rheumatic heart disease. This review outlines the burden of heart
      failure in Africa and highlights the opportunity to expand diagnosis through the
      use of biomarkers, in particular natriuretic peptides. This builds on the success
      of point-of-care testing in human immunodeficiency virus and tuberculosis which
      have been extensively deployed in community settings in Africa.

PMID- 25598185
TI  - Schisanhenol derivatives and their biological evaluation against tobacco mosaic
      virus (TMV).
AB  - Schisanhenol (Sol) was isolated from Schisandra rubriflora, and a series of
      derivatives (1-16, 15a-16a, and 15b-16b) were designed and prepared by chemical
      modification. The curative and protective effects of these dibenzocyclooctadiene
      lignan analogues against tobacco mosaic virus (TMV) were evaluated. Most
      analogues exhibited stronger protective effects than the positive control
      ningnanmycin. Dibromoschisanhenol (6) at 0.25mM exhibited the strongest
      protective activity (83.5+/-1.8% at 0.25mM), and 14-(3, 5-dibenzyloxy)
      benzoyloxyschisanhenol (16) showed a significant curative effect (78.0+/-3.8% at
      0.15mM) that was much stronger than that of the commercial virucide ningnanmycin.
      This study is the first to demonstrate that natural dibenzocyclooctadiene lignans
      and analogues are active against plant viruses. 

PMID- 25598186
TI  - Three new labdane-type diterpene glycosides from fruits of Rubus chingii and
      their cytotoxic activities against five humor cell lines.
AB  - Three new labdane-type diterpene glycosides, 15,18-di-O-beta-d-glucopyranosyl
      13(E)-ent-labda-7(8),13(14)-diene-3beta,15,18-triol (1), 15,18-di-O-beta-d
      glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3beta,15,18-triol (2), and 15-O
      beta-d-apiofuranosyl-(1->2)-beta-d-glucopyranosyl-18-O-beta-d-glucopyranosyl
      13(E)-ent-labda-8(9),13(14)-diene-3beta,15,18-triol (3), were isolated from the
      fruits of Rubus chingii. Their structures were elucidated on the basis of
      spectroscopic data and chemical methods. The cytotoxic activities of compounds 1
      3 were evaluated against five human tumor cell lines (HCT-8, BGC-823, A549, and
      A2780). Compounds 3 showed cytotoxic activity against A549 with an IC50 value of
      2.32MUM.

PMID- 25598187
TI  - Antimicrobial and cytotoxic phenolics and phenolic glycosides from Sargentodoxa
      cuneata.
AB  - Five new phenolic glycosides, Sargentodosides A-E, and two new dihydronaphthalene
      lignans, Sargentodognans F-G, together with thirty-two known phenolic compounds
      were isolated from the 60% ethanol extracts of Sargentodoxa cuneata. Their
      structures including absolute configurations were determined by spectroscopic
      analysis and electronic circular dichroism experiments. In bioscreening
      experiments, twelve compounds (22-26, 29, 33-34, 36, 38) exhibited antibacterial
      activities against S. aureus ATCC 29213 with minimum inhibitory concentration
      (MIC) values of 2-516MUg/mL. And compound 29 showed the highest antibacterial
      activity against S. aureus ATCC 29213 with MIC values of 2MUg/mL, while the MIC
      values of levofloxacin was 8MUg/mL. Three compounds (29, 33, 36) exhibited
      antibacterial activities against S. aureus ATCC 25923 with MIC values of 256
      516MUg/mL. Two compounds (29, 33) exhibited antibacterial activities against A.
      baumanii ATCC 19606 with MIC values of 128-516MUg/mL. However, no compound
      exhibited antimicrobial activities against C. albicans ATCC 10231. Moreover,
      three compounds (10, 25, 36) exhibited significant inhibition of proliferation in
      the two cell lines Hela and Siha, and showed stronger inhibitive activity of
      these two selected cell lines than cisplatin in the cytotoxic assay. Thus, S.
      cuneata is a potential plant source for further research targeting bacteria and
      cancer diseases. 

PMID- 25598188
TI  - Inhibitory effects of polyphenols from grape pomace extract on collagenase and
      elastase activity.
AB  - Breakdown and disorganization of extracellular matrix proteins like collagen,
      fibronectin and elastin are main characteristics of skin aging due to the
      enhanced activation of proteolytic enzymes such as collagenases and elastases.
      Inhibition of their enzymatic activities by natural plant compounds might be a
      promising approach to prevent extrinsic skin aging. Especially polyphenols are
      supposed to interact with those enzymes due to their molecular nature. In our
      investigation, extracts of pomace from Riesling grapes were analyzed for their
      inhibitory properties on collagenase as well as elastase. Crude grape pomace
      extract showed a dose-dependent inhibitory activity against both enzymes with
      IC50-values of 20.3MUg/ml and 14.7MUg/ml for collagenase and elastase activity,
      respectively. The extracts were fractionated into four fractions containing
      phenolic compounds differing in chemical structure and polarity. Except for the
      stilbene containing fraction, all other fractions showed inhibitory effects on
      both enzyme activities. The most pronounced impact was found for the hydrophilic
      low molecular weight polyphenols containing the free phenolic acids. In
      particular, gallic acid showed considerable inhibition values. EGCG was used as a
      positive control and showed a dose-dependent inhibition of collagenase activity
      (IC50=0.9mM). 

PMID- 25598190
TI  - Highly cold-active pectinases under wine-like conditions from non-Saccharomyces
      yeasts for enzymatic production during winemaking.
AB  - The influence of oenological factors on cold-active pectinases from 15
      preselected indigenous yeasts belonging to Aureobasidium pullulans, Filobasidium
      capsuligenum, Rhodotorula dairenensis, Cryptococcus saitoi and Saccharomyces
      cerevisiae was investigated. Pectinolytic enzymes were constitutive or partially
      constitutive; and high glucose concentration (200 g l(-1) ) did not affect or
      increased pectinase production at 12 degrees C and pH 3.5 (up to 113.9 U mg(-1) )
      only in A. pullulans strains. SO2 (120 mg l(-1) ) slightly affected the growth of
      A. pullulans strains but did not affect pectinase production levels. Ethanol
      (15%) barely affected pectinase activity of A. pullulans strains but diminished
      relative activity to 12-79% of basidiomycetous yeasts. Moreover, non
      Saccharomyces strains showed promising properties of oenological interest. This
      study demonstrates that cold-active pectinases from some A. pullulans strains
      were able to remain active at glucose, ethanol and SO2 concentrations usually
      found in vinification, and suggests their potential use as processing aids for
      low-temperature winemaking. SIGNIFICANCE AND IMPACT OF THE STUDY: Nowadays, there
      is increasing interest in low-temperature winemaking. Nevertheless, commercial
      oenological pectinases, produced by fungi, are rarely active at low temperatures.
      Cold-active pectinases that are stable under vinification conditions are needed.
      This study indicated that cold-active and acid-tolerant pectinases from non
      Saccharomcyes yeasts were able to remain active at glucose, ethanol and SO2
      concentrations usually found in winemaking. Furthermore, not only are these
      yeasts a source of cold-active pectinases, but the yeasts themselves are also
      potential adjunct cultures for oenology to produce these enzymes during cold
      winemaking.

PMID- 25598191
TI  - Mass spectrometry evaluation of the hepcidin-25 assay in the differential
      diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of
      inflammation in elderly patients.
AB  - In this study, mass spectrometry was used to evaluate the hepcidin-25 assay in
      the differential diagnosis of iron deficiency anaemia with concurrent
      inflammation and anaemia of inflammation in elderly patients using the absence of
      stainable bone marrow iron as the gold standard criterion for iron deficiency
      (ID). In addition, correlation coefficients for hepcidin-25 vs. haematimetric and
      biochemical iron parameters, and C-reactive protein (CRP) were determined. The
      optimal cut-off for hepcidin-25 was 31.5 ng/mL corresponding to a sensitivity and
      specificity of 82% and 95%, respectively, for ID. For ferritin, a sensitivity and
      specificity of 70% and 100%, respectively, correspond to an optimal cut-off of
      41.5 MUg/L. Receiver operating characteristics curve analysis revealed that mass
      spectrometry analysis of hepcidin-25 does not appear to be superior to ferritin
      in the diagnosis of ID in elderly anaemic patients with concurrent inflammation.
      Hepcidin-25 shows a strong positive correlation with ferritin, and also
      correlates positively with CRP, in this patient population.

PMID- 25598189
TI  - Jonquailine, a new pretazettine-type alkaloid isolated from Narcissus jonquilla
      quail, with activity against drug-resistant cancer.
AB  - A new alkaloid, belonging to the pretazettine group of Amaryllidaceae alkaloids,
      was isolated from dried bulbs of Narcissus jonquilla quail and named jonquailine.
      Its structure, including the absolute configuration, was elucidated using various
      NMR, ECD and ESI MS techniques. Initial biological evaluation revealed
      significant antiproliferative effects against glioblastoma, melanoma, uterine
      sarcoma and non-small-cell lung cancer cells displaying various forms of drug
      resistance, including resistance to apoptosis and multi-drug resistance.
      Jonquailine was also found to synergize with paclitaxel in its antiproliferative
      action against drug-resistant lung cancer cells. The results obtained compared
      with literature data also showed that the hydroxylation at C-8 is an important
      feature for the anticancer activity but this seems unaffected by the
      stereochemistry or the acetalization of the lactol.

PMID- 25598192
TI  - Evaluation of the Flinders Technology Associates Cards for Storage and
      Temperature Challenges in Field Conditions for Foot-and-Mouth Disease Virus
      Surveillance.
AB  - Foot-and-mouth disease virus (FMDV) samples transported to the laboratory from
      far and inaccessible areas for diagnosis and identification of FMDV pose a major
      problem in a tropical country like India, where wide fluctuation of temperature
      over a large geographical area is common. Inadequate storage methods lead to
      spoilage of FMDV samples collected from clinically positive animals in the field.
      Such samples are declared as non-typeable by the typing laboratories with the
      consequent loss of valuable epidemiological data. In this study, an attempt was
      made to evaluate the robustness of Flinders Technology Associates (FTA) cards for
      storage and transportation of FMDV samples in different climatic conditions which
      will be useful for FMDV surveillance. Simulation transport studies were conducted
      using FTA impregnated FMDV samples during post-monsoon (September-October 2010)
      and summer season (May-June 2012). FMDV genome or serotype could be identified
      from the FTA cards after the simulation transport studies with varying
      temperature (22-45 degrees C) and relative humidity (20-100%). The stability of
      the viral RNA, the absence of infectivity and ease of processing the sample for
      molecular methods make the FTA cards an useful option for transport of FMDV
      genome for identification and type determination. The method can be used
      routinely for FMDV research as it is economical and the cards can be transported
      easily in envelopes by regular courier/postal systems. The absence of live virus
      in FTA card can be viewed as an advantage as it restricts the risk of
      transmission of live virus.

PMID- 25598193
TI  - Activated endothelial cells limit inflammatory response, but increase
      chemoattractant potential and bacterial clearance by human monocytes.
AB  - Inflammation is the normal immune response of vascularized tissues to damage and
      bacterial products, for which leukocyte transendothelial migration (TEM) is
      critical. The effects of cell-to-cell contact seen in both leukocyte and
      endothelial cells include cytoskeleton rearrangement, and dynamic expression of
      adhesion molecules and metalloproteinases. TEM induces expression of anti
      apoptotic molecules, costimulatory molecules associated with antigen
      presentation, and pattern recognition receptors (PRR), such as TLR-4, in
      monocytes. However, little is known about how TLR-4 increment operates in
      monocytes during an inflammatory response. To understand it better, we used an in
      vitro model in which monocytes crossed a layer of IL-1beta stimulated Human
      Umbilical Vein Endothelial Cells (HUVEC). After TEM, monocytes were tested for
      the secretion of inflammatory cytokines and chemokines, their phenotype (CD14,
      CD16, TLR-4 expression), and TLR-4 canonical [Nuclear Factor kappa B, (NF-kappaB)
      pathway] and non-canonical [p38, extracellular signal-regulated kinases (ERK) 1/2
      pathway] signal transduction induced by lipopolysaccharide (LPS). Phagocytosis
      and bacterial clearance were also measured. There was diminished secretion of LPS
      induced inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) and higher
      secretion of chemokines (CXCL8/IL-8 and CCL2/MCP-1) in supernatant of TEM
      monocytes. These changes were accompanied by increases in TLR-4, CD14 (surfaces
      expression), p38, and ERK1/2 phosphorylated cytoplasmic forms, without affecting
      NF-kappaB activation. It also increased bacterial clearance after TEM by an O2 
      independent mechanism. The data suggest that interaction between endothelial
      cells and monocytes fine-tunes the inflammatory response and promotes bacterial
      elimination. 

PMID- 25598194
TI  - Influence of footwear and equipment on stride length and range of motion of
      ankle, knee and hip joint.
AB  - PURPOSE: Footwear and equipment worn by military personnel is of importance for
      them to be able to meet the physical demands specific to their profession daily
      activities. The aim of the present study was to investigate by means of gait
      analysis how army-provided footwear and equipment influence the range of motion
      of hip, knee and ankle joints as well as stride length. METHODS: Thirty-two
      soldiers were subjected to gait analysis on a treadmill by way of video
      recordings and goniometric measurements. RESULTS: The stride length increased
      when military shoes are worn. We found no influence on stride length in
      connection to increased loading. The weight of the shoes represents the decisive
      factor. Neither shoes nor equipment changed the range of motion of the knee
      joint. Weight of equipment affected range of motion of the hip joint. The range
      of motion of the upper and lower ankle joints was mainly influenced by the
      properties of the shoes. CONCLUSIONS: Military footwear and weight of equipment
      influence stride length and range of motion of joints of the lower extremities in
      a specific way. Shape of material is the decisive factor.

PMID- 25598195
TI  - The sensitivity to change over time of the Amsterdam IADL Questionnaire((c)).
AB  - INTRODUCTION: This study aimed to investigate the sensitivity to change over time
      of a new informant-based instrument to assess instrumental activities of daily
      living (IADL) during the course of dementia: the Amsterdam IADL
      Questionnaire((c)) (A-IADL-Q). METHODS: Participants (n = 102) were patients and
      their informants who visited the Alzheimer Center of the VU University Medical
      Center. Linear mixed models with random effects were used to relate longitudinal
      change on the A-IADL-Q to diagnosis and to longitudinal change in cognitive
      measures. RESULTS: We found longitudinal change on the A-IADL-Q to differ between
      diagnosis (P = .003), with dementia patients showing the fastest rate of decline
      (P < .001). In addition, we found longitudinal change on the A-IADL-Q to be
      related to longitudinal change in cognitive measures (global cognition: P < .001;
      memory: P = .024; executive functioning: P = .028). DISCUSSION: Findings indicate
      the A-IADL-Q is sensitive to change over time in IADL functioning and can be used
      in evaluating treatment effects and assessing individual disease progress.

PMID- 25598196
TI  - Reply: To PMID 24824965.

PMID- 25598198
TI  - The enantioselective construction of tetracyclic diterpene skeletons with Friedel
      Crafts alkylation and palladium-catalyzed cycloalkenylation reactions.
AB  - Due to the profound extent to which natural products inspire medicinal chemists
      in drug discovery, there is demand for innovative syntheses of these often
      complex materials. This article describes the synthesis of tricarbocyclic natural
      product architectures through an extension of the enantioselective Birch-Cope
      sequence with intramolecular Friedel-Crafts alkylation reactions. Additionally,
      palladium-catalyzed enol silane cycloalkenylation of the tricarbocyclic
      structures afforded the challenging bicyclo[3.2.1]octane C/D ring system found in
      the gibberellins and the ent-kauranes, two natural products with diverse
      medicinal value. In the case of the ent-kaurane derivative, an unprecedented
      alkene rearrangement converted four alkene isomers to one final product. 

PMID- 25598197
TI  - Kinesiophobia in pre-operative patients with cervical discopathy and coexisting
      degenerative changes in relation to pain-related variables, psychological state
      and sports activity.
AB  - BACKGROUND: No research group has ever investigated the level of kinesiophobia in
      a well defined group of preoperative patients treated due to cervical discopathy
      and degenerative spine disease, confirmed by X-ray and magnetic resonance imaging
      (MRI) examinations. We aimed to investigate the degree of kinesiophobia and the
      differences in pain-related and psychosocial characteristics between patients
      with high and low levels of kinesiophobia, in relation to factors commonly
      associated with neck pain. MATERIAL/METHODS: Sixty-five consecutive patients with
      cervical discopathy and coexisting degenerative changes were assessed pre
      surgically. The mean pain duration was 31.7 SD 34.0 months. Patients completed
      the Polish versions of the Tampa Scale for Kinesiophobia (TSK-PL) on 2 occasions,
      and the following once: Neck Disability Index (NDI-PL), State-Trait Anxiety
      Inventory (STAI-PL), Coping Strategies Questionnaire (CSQ-PL), and the Visual
      Analogue Scale (VAS-PL). RESULTS: A high level of kinesiophobia was indicated in
      81.5% and 87.7% of patients in first and second completion, respectively.
      Patients with high and low kinesiophobia differ in regards to the recreation
      section of NDI-PL (p=0.012), gender (p=0.043), and sports activity (p=0.024).
      Correlations were identified between TSK-PL and marital status (p=0.023) and
      sports activity (p=0.024). CONCLUSIONS: Kinesiophobia levels are higher in
      patients with chronic cervical pain before surgical treatment. Fear of movement
      tends to be higher in women and among patients avoiding sports recreation before
      surgical treatment. Although sports activity and socio-demographic data are
      predictors of kinesiophobia, psychological, pain-related, and clinical data are
      not. These findings should be considered when planning rehabilitation after
      surgical treatment of cervical discopathy and coexisting degenerative changes.

PMID- 25598200
TI  - Egg proteins as allergens and the effects of the food matrix and processing.
AB  - Hen eggs are an important and inexpensive source of high-quality proteins in the
      human diet. Egg, either as a whole or its constituents (egg yolk and white), is a
      key ingredient in many food products by virtue of its nutritional value and
      unique functional properties, such as emulsifying, foaming, and gelling.
      Nevertheless, egg is also known because of its allergenic potential and, in fact,
      it is the second most frequent source of allergic reactions, particularly in
      children. This review deals with the structural or functional properties of egg
      proteins that make them strong allergens. Their ability to sensitize and/or
      elicit allergic reactions is linked to their resistance to gastroduodenal
      digestion, which ultimately allows them to interact with the intestinal mucosa
      where absorption occurs. The factors that affect protein digestibility, whether
      increasing it, decreasing it, or inducing a different proteolysis pattern, and
      their influence on their capacity to induce or trigger an allergic reaction are
      discussed. Special attention is paid to the effect of the food matrix and the
      processing practices on the capacity of egg proteins to modulate the immune
      response. 

PMID- 25598199
TI  - Telomere length in the two extremes of abnormal fetal growth and the programming
      effect of maternal arterial hypertension.
AB  - We tested the hypothesis that leukocyte telomere length (LTL) is associated with
      birth weight in both extremes of abnormal fetal growth: small (SGA) and large for
      gestational age newborns (LGA). Clinical and laboratory variables of the mothers
      and the neonates were explored; 45 newborns with appropriate weight for
      gestational age (AGA), 12 SGA and 12 LGA were included. Whether the differences
      might be explained by variation in OBFC1 (rs9419958) and CTC1 (rs3027234) genes
      associated with LTL was determined. A significant association between birth
      weight and LTL was observed; LTL was significantly shorter in LGA newborns (1.01
      +/- 0.12) compared with SGA (1.73 +/- 0.19) p < 0.005, mean +/- SE. Maternal
      (Spearman R = -0.6, p = 0.03) and neonatal LTL (R = -0.25, p = 0.03) were
      significantly and inversely correlated with maternal history of arterial
      hypertension in previous gestations. Neonatal LTL was not significantly
      associated with either rs9419950 or rs3027234, suggesting that the association
      between neonatal LTL and birth weight is not influenced by genetic variation in
      genes that modify the interindividual LTL. In conclusion, telomere biology seems
      to be modulated by abnormal fetal growth; modifications in telomere length might
      be programmed by an adverse environment in utero. 

PMID- 25598201
TI  - Quantitative farm-to-fork risk assessment model for norovirus and hepatitis A
      virus in European leafy green vegetable and berry fruit supply chains.
AB  - Fresh produce that is contaminated with viruses may lead to infection and viral
      gastroenteritis or hepatitis when consumed raw. It is thus important to reduce
      virus numbers on these foods. Prevention of virus contamination in fresh produce
      production and processing may be more effective than treatment, as sufficient
      virus removal or inactivation by post-harvest treatment requires high doses that
      may adversely affect food quality. To date knowledge of the contribution of
      various potential contamination routes is lacking. A risk assessment model was
      developed for human norovirus, hepatitis A virus and human adenovirus in
      raspberry and salad vegetable supply chains to quantify contributions of
      potential contamination sources to the contamination of produce at retail. These
      models were used to estimate public health risks. Model parameterization was
      based on monitoring data from European supply chains and literature data. No
      human pathogenic viruses were found in the soft fruit supply chains; human
      adenovirus (hAdV) was detected, which was additionally monitored as an indicator
      of fecal pollution to assess the contribution of potential contamination points.
      Estimated risks per serving of lettuce based on the models were 3*10(-4) (6*10(
      6)-5*10(-3)) for NoV infection and 3*10(-8) (7*10(-10)-3*10(-6)) for hepatitis A
      jaundice. The contribution to virus contamination of hand-contact was larger as
      compared with the contribution of irrigation, the conveyor belt or the water used
      for produce rinsing. In conclusion, viral contamination in the lettuce and soft
      fruit supply chains occurred and estimated health risks were generally low.
      Nevertheless, the 97.5% upper limit for the estimated NoV contamination of
      lettuce suggested that infection risks up to 50% per serving might occur. Our
      study suggests that attention to full compliance for hand hygiene will improve
      fresh produce safety related to virus risks most as compared to the other
      examined sources, given the monitoring results. This effect will be further aided
      by compliance with other hygiene and water quality regulations in production and
      processing facilities. 

PMID- 25598202
TI  - MiR-21 alleviates secondary blood-brain barrier damage after traumatic brain
      injury in rats.
AB  - Our recent studies have identified increased expression of miR-21 in brain
      following traumatic brain injury (TBI), which alleviated brain edema that related
      to the blood-brain barrier (BBB) leakage. To analyze the potential effect of miR
      21 on secondary BBB damage after TBI, we employed the fluid percussion injury rat
      model and manipulated the expression level of miR-21 in brain. We found that miR
      21 level in brain microvascular endothelial cells (BMVECs) in lesioned cerebral
      cortex can be upregulated or downregulated by intracerebroventricular infusion of
      miR-21 agomir or antagomir. Upregulated miR-21 level conferred a better
      neurological outcome of TBI, and alleviated TBI-induced secondary BBB damage and
      loss of tight junction proteins. To explore the molecular mechanism underlying
      this protective effect, we detected the impact of miR-21 on the expression of
      Angiopoietin-1(Ang-1) and Tie-2, which can promote the expression of tight
      junction proteins and amplify BBB stabilization. We found that miR-21 exerts the
      protective effect on BBB by activating the Ang-1/Tie-2 axis in BMVECs. Thus, miR
      21 could be a potential therapeutic target for interventions of secondary BBB
      damage after TBI. 

PMID- 25598203
TI  - Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and
      causes blood-brain barrier damage and cognitive impairment in rats.
AB  - With the rapid increase in the number of mobile phone users, the potential
      adverse effects of the electromagnetic field radiation emitted by a mobile phone
      has become a serious concern. This study demonstrated, for the first time, the
      blood-brain barrier and cognitive changes in rats exposed to 900 MHz
      electromagnetic field (EMF) and aims to elucidate the potential molecular pathway
      underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to
      a 900 MHz, 1 mW/cm(2) EMF or sham (unexposed) for 14 or 28 days (3h per day). The
      specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2
      W/kg (locally in the head). In addition, the Morris water maze test was used to
      examine spatial memory performance determination. Morphological changes were
      investigated by examining ultrastructural changes in the hippocampus and cortex,
      and the Evans Blue assay was used to assess blood brain barrier (BBB) damage.
      Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons
      and albumin extravasation detection. Western blot was used to determine HO-1
      expression, phosphorylated ERK expression and the upstream mediator, mkp-1
      expression. We found that the frequency of crossing platforms and the percentage
      of time spent in the target quadrant were lower in rats exposed to EMF for 28
      days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28
      days of EMF exposure induced cellular edema and neuronal cell organelle
      degeneration in the rat. In addition, damaged BBB permeability, which resulted in
      albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus,
      for the first time, we found that EMF exposure for 28 days induced the expression
      of mkp-1, resulting in ERK dephosphorylation. Taken together, these results
      demonstrated that exposure to 900 MHz EMF radiation for 28 days can significantly
      impair spatial memory and damage BBB permeability in rat by activating the mkp
      1/ERK pathway.

PMID- 25598204
TI  - Constriction and dysfunction of pial arterioles after regional hemorrhage in the
      subarachnoid space.
AB  - Increasing evidence indicates that poor outcomes after brain hemorrhage,
      especially after subarachnoid hemorrhage (SAH), can be attributed largely to
      dysfunction of the cerebral microcirculation. However, the cause of this
      dysfunction remains unclear. Here, we investigated changes in the cerebral
      microcirculation after regional hemorrhage in the subarachnoid space using the
      closed cranial window technique in mice. A single pial arteriole on the surface
      of the brain was punctured to induce a regional hemorrhage in the subarachnoid
      space. Physiological parameters were monitored during the procedure, and
      microvessel diameter was measured after hemorrhage. The vasoreactivity of the
      arterioles in response to hypercapnia as well as to topical application of the
      vasodilator acetylcholine (ACh) and S-nitroso-N-acetyl-penicillamine (SNAP) were
      assessed. The constriction of pial arterioles was detected without changes in
      other physiological parameters. Decreased reactivity of pial arterioles to all of
      the applied vasodilatory stimuli was observed after hemorrhage. Our results
      indicate that regional hemorrhage in the subarachnoid space can induce the
      vasospasm of microvessels and also reduce the vasoreactivity of pial arterioles. 

PMID- 25598206
TI  - Automatic prediction regarding the next state of a visual object:
      Electrophysiological indicators of prediction match and mismatch.
AB  - Behavioral phenomena such as representational momentum suggest that the brain can
      automatically predict the next state of a visual object, based on sequential
      rules embedded in its preceding spatiotemporal context. To identify
      electrophysiological indicators of automatic visual prediction in terms of
      prediction match and mismatch, we recorded event-related brain potentials (ERPs)
      while participants passively viewed three types of task-irrelevant sequences of a
      bar stimulus: (1) an oddball sequence, which contained a sequential rule defined
      by stimulus repetition, providing repetition-rule-conforming (standard) and 
      violating (deviant) stimuli; (2) a rotating-oddball sequence, which contained a
      sequential rule defined by stimulus change (i.e., rotation), providing change
      rule-conforming (regular) and -violating (irregular) stimuli; and (3) a random
      sequence, which did not contain a sequential rule, providing a neutral (control)
      stimulus. This protocol allowed us to expect that (1) an ERP effect that reflects
      a prediction-mismatch process should be exclusively observed in both the deviant
      minus-control and irregular-minus-control comparisons and (2) an ERP effect that
      reflects a prediction-match process should be exclusively observed in both the
      standard-minus-control and regular-minus-control comparisons. The results showed
      that the ERP effect that met the criterion for prediction mismatch was an
      occipito-temporal negative deflection at around 170-300ms (visual mismatch
      negativity), while the ERP effect that met the criterion for prediction match was
      a frontal/central negative deflection at around 150-270ms (probably, the
      reduction of P2). These two contrasting ERP effects support a hypothetical view
      that automatic visual prediction would involve both an increase in the neural
      response to prediction-incongruent (i.e., novel) events and a decrease in the
      neural response to prediction-congruent (i.e., redundant) events. This article is
      part of a Special Issue entitled SI: Prediction and Attention. 

PMID- 25598207
TI  - Theoretical studies on the AnO2(n+) (An = U, Np; n = 1, 2) complexes with di-(2
      ethylhexyl)phosphoric acid.
AB  - Actinide separation in spent nuclear fuel reprocessing is essential for the
      closed nuclear fuel cycle. Organophosphorus reagents have been found to exhibit
      strong affinities for actinides in experiments. In this work, the extraction
      complexes of AnO2(n+) (An = U, Np; n = 1, 2) with the traditional
      organophosphorus ligand HDEHP (di-(2-ethylhexyl)phosphoric acid) have been
      investigated using density functional theory together with scalar-relativistic
      effective core potentials (ECPs) for actinide elements. According to our
      calculations, the HDEHP dimer prefers to act as a bidentate ligand in most of the
      studied complexes. HDEHP ligands show a higher extraction ability for An(vi) over
      An(v), and the formation of Np(vi) complexes is slightly more favorable than
      those of U(vi) analogues, which is mainly attributed to the stronger donor
      acceptor interaction in Np(vi) complexes. The intramolecular hydrogen bonds play
      a significant role in the stability of the 1 : 1 type complexes AnO2(HL)2(NO3)2
      (L = DEHP(-)). Moreover, AnO2(HL)2(NO3)2 are the most stable species in nitrate
      rich acid solutions, while at low nitric acid concentrations, the complexing
      reaction of AnO2(H2O)5(2+) + 2(HL)2 -> AnO2(HL2)2 + 2H(+) + 5H2O is probably the
      dominant reaction in the extraction process. Our results can help to understand
      the speciation of actinyl complexes in real solvent extraction of actinides with
      HDEHP at the molecular level. 

PMID- 25598205
TI  - Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes
      in rat brain under stress.
AB  - Knowledge of the antioxidant defense in the stress-responding structures of the
      CNS is of crucial importance, since oxidative damage is a phenomenon accompanying
      many stress-related disorders. Regulation of antioxidative and anti-inflammatory
      defense through Nrf2 (nuclear factor 2 eritroid related factor 2) pathway has
      emerged as a promising approach for neuroprotection. In this study, we used
      chronic social isolation of male Wistar rats to induce depressive-like behavior.
      We hypothesized that Nrf2-Keap1 pathway is compromised in the limbic brain after
      prolonged stress. Since subcellular trafficking of Nrf2 and its inhibitor Keap1
      (Kelch ECH associating protein 1) is essential for the activation of Nrf2, we
      determined their protein level in cytosolic and nuclear compartments of
      hippocampus and prefrontal cortex (PFC). We also determined mRNA levels of Nrf2
      regulated genes involved in the production and utilization of glutathione,
      glutamate cysteine ligase (Gclm), glutathione S-transferase (Gsta3) and
      glutathione reductase (Gsr). Our results showed that chronic isolation induced
      anxiety and depressive-like behavior, decreased Nrf2 and in parallel increased
      Keap1 and nuclear factor kappa B (NFkappaB) in the hippocampus, which were not
      accompanied by expression profiles of Nrf2-regulated genes. Chronically stressed
      rats challenged with acute stress failed to induce any response of examined genes
      in either of brain structures, even though Nrf2/Keap1 was altered, while in naive
      animals Nrf2 activity corresponded with an expression of Nrf2-regulated genes.
      Our results reveal maladaptive character of chronic stress at Nrf2/Keap1 level
      followed by pro-inflammatory conditions, and suggest a possible role of these
      alterations in pathogenesis of depressive/anxiety disorders. 

PMID- 25598208
TI  - Dip-pen patterning of poly(9,9-dioctylfluorene) chain-conformation-based nano
      photonic elements.
AB  - Metamaterials are a promising new class of materials, in which sub-wavelength
      physical structures, rather than variations in chemical composition, can be used
      to modify the nature of their interaction with electromagnetic radiation. Here we
      show that a metamaterials approach, using a discrete physical geometry
      (conformation) of the segments of a polymer chain as the vector for a substantial
      refractive index change, can be used to enable visible wavelength, conjugated
      polymer photonic elements. In particular, we demonstrate that a novel form of dip
      pen nanolithography provides an effective means to pattern the so-called beta
      phase conformation in poly(9,9-dioctylfluorene) thin films. This can be done on
      length scales <=500 nm, as required to fabricate a variety of such elements, two
      of which are theoretically modelled using complex photonic dispersion
      calculations. 

PMID- 25598209
TI  - The electrochemical transfer of CVD-graphene using agarose gel as solid
      electrolyte and mechanical support layer.
AB  - The transfer of chemical vapor deposition (CVD)-grown graphene is the
      prerequisite for many applications. Herein, we introduce a simple and eco
      friendly electrochemical technique to transfer graphene using agarose gel as the
      solid electrolyte and a mechanical support layer for graphene sheets. This
      transfer technique will be a perfect candidate for the industrial applications of
      graphene. 

PMID- 25598210
TI  - Descriptive epidemiology of physical activity rates in multiple sclerosis.
AB  - BACKGROUND: Persons with multiple sclerosis (MS) engage in substantially less
      overall physical activity than healthy controls, but there is little information
      on public health rates of physical activity necessary for health benefits.
      PURPOSE: This study examined the rates of insufficient, moderate, and sufficient
      physical activity in persons with MS compared with healthy controls. METHOD:
      Secondary analysis of data from participants with MS (n = 1521) and healthy
      controls (n = 162) who completed the Godin Leisure-Time Exercise Questionnaire
      (GLTEQ) as part of a questionnaire battery in 14 previous investigations.
      RESULTS: There were statistically significant differences in overall GLTEQ scores
      (F1,1666 = 96.8, P < 0.001, d = 0.83) and rates of physical activity (chi(2) (2,
      N = 1683) = 94.2, P < 0.001) between MS and control groups. The rates of
      insufficient, moderate, and sufficient physical activity in the MS group were
      58.0%, 15.2%, and 26.8%, respectively. Those with MS were 2.5 times more likely
      to report insufficient physical activity and 2.3 times less likely to report
      sufficient physical activity than controls. CONCLUSION: The majority of persons
      with MS were insufficiently physically active, and this segment represents the
      largest opportunity for successful behavior change and accumulation of associated
      health benefits.

PMID- 25598211
TI  - Decompression sickness in breath-hold diving, and its probable connection to the
      growth and dissolution of small arterial gas emboli.
AB  - We solved the Laplace equation for the radius of an arterial gas embolism (AGE),
      during and after breath-hold diving. We used a simple three-region diffusion
      model for the AGE, and applied our results to two types of breath-hold dives:
      single, very deep competitive-level dives and repetitive shallower breath-hold
      dives similar to those carried out by indigenous commercial pearl divers in the
      South Pacific. Because of the effect of surface tension, AGEs tend to dissolve in
      arterial blood when arteries remote from supersaturated tissue. However if,
      before fully dissolving, they reach the capillary beds that perfuse the brain and
      the inner ear, they may become inflated with inert gas that is transferred into
      them from these contiguous temporarily supersaturated tissues. By using simple
      kinetic models of cerebral and inner ear tissue, the nitrogen tissue partial
      pressures during and after the dive(s) were determined. These were used to
      theoretically calculate AGE growth and dissolution curves for AGEs lodged in
      capillaries of the brain and inner ear. From these curves it was found that both
      cerebral and inner ear decompression sickness are expected to occur occasionally
      in single competitive-level dives. It was also determined from these curves that
      for the commercial repetitive dives considered, the duration of the surface
      interval (the time interval separating individual repetitive dives from one
      another) was a key determinant, as to whether inner ear and/or cerebral
      decompression sickness arose. Our predictions both for single competitive-level
      and repetitive commercial breath-hold diving were consistent with what is known
      about the incidence of cerebral and inner ear decompression sickness in these
      forms of diving. 

PMID- 25598212
TI  - Evaluation for roles of neurosteroids in modulating forebrain mechanisms
      controlling vasopressin secretion and related phenomena in conscious rats.
AB  - Anteroventral third ventricular region (AV3V) that regulates autonomic functions
      through a GABAergic mechanism possesses neuroactive steroid (NS)-synthesizing
      ability. Although NS can exert effects by acting on a certain type of GABAA
      receptor (R), it is not clear whether NS may operate to modulate AV3V GABAergic
      activity for controlling autonomic functions. This study aimed to investigate the
      issue. AV3V infusion with a GABAA antagonist bicuculline increased plasma
      vasopressin (AVP), glucose, blood pressure (BP), and heart rate in rats. These
      events were abolished by preinjecting its agonist muscimol, whereas the infusion
      with allopregnanolone, a NS capable of potentiating GABAA-R function, affected
      none of the variables in the absence or presence of such bicuculline actions.
      Similarly, AV3V infusion with pregnanolone sulfate, a NS capable of antagonizing
      GABAA-R, produced no effect on those variables. AV3V infusion with muscimol was
      effective in inhibiting the responses of plasma AVP or glucose, or BP to an
      osmotic loading or bleeding. However, AV3V infusion with aminoglutethimide, a NS
      synthesis inhibitor, did not affect any of the variables in the absence or
      presence of those stimuli. These results suggest that NS may not cause acute
      effects on the AV3V GABAergic mechanism involved in regulating AVP release and
      other autonomic function. 

PMID- 25598213
TI  - Conclusion of "Nordic walking for geriatric rehabilitation: a randomized pilot
      trial" is based on faulty statistical analysis and is inaccurate.

PMID- 25598214
TI  - A novel role for central ACBP/DBI as a regulator of long-chain fatty acid
      metabolism in astrocytes.
AB  - Acyl-CoA-binding protein (ACBP) is a ubiquitously expressed protein that binds
      intracellular acyl-CoA esters. Several studies have suggested that ACBP acts as
      an acyl-CoA pool former and regulates long-chain fatty acids (LCFA) metabolism in
      peripheral tissues. In the brain, ACBP is known as Diazepam-Binding Inhibitor, a
      secreted peptide acting as an allosteric modulator of the GABAA receptor.
      However, its role in central LCFA metabolism remains unknown. In the present
      study, we investigated ACBP cellular expression, ACBP regulation of LCFA
      intracellular metabolism, FA profile, and FA metabolism-related gene expression
      using ACBP-deficient and control mice. ACBP was mainly found in astrocytes with
      high expression levels in the mediobasal hypothalamus. We demonstrate that ACBP
      deficiency alters the central LCFA-CoA profile and impairs unsaturated (oleate,
      linolenate) but not saturated (palmitate, stearate) LCFA metabolic fluxes in
      hypothalamic slices and astrocyte cultures. In addition, lack of ACBP differently
      affects the expression of genes involved in FA metabolism in cortical versus
      hypothalamic astrocytes. Finally, ACBP deficiency increases FA content and
      impairs their release in response to palmitate in hypothalamic astrocytes.
      Collectively, these findings reveal for the first time that central ACBP acts as
      a regulator of LCFA intracellular metabolism in astrocytes. Acyl-CoA-binding
      protein (ACBP) or diazepam-binding inhibitor is a secreted peptide acting
      centrally as a GABAA allosteric modulator. Using brain slices, cortical, and
      hypothalamic astrocyte cultures from ACBP KO mice, we demonstrate that ACBP
      mainly localizes in astrocytes and regulates unsaturated but not saturated long
      chain fatty acids (LCFA) metabolism. In addition, ACBP deficiency alters FA
      metabolism-related genes and results in intracellular FA accumulation while
      affecting their release. Our results support a novel role for ACBP in brain lipid
      metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG,
      triacylglycerol. 

PMID- 25598215
TI  - Bilateral internal mammary artery grafting in obese: outcomes, concerns and
      controversies.
AB  - Obese patients are generally considered unsuitable to receive bilateral internal
      mammary arteries (BIMA) during coronary artery bypass grafting (CABG) due to the
      perceived vulnerability to sternal wound infection and lack of evidence
      supporting long-term survival benefit. However, no consistent evidence currently
      discourages the use of BIMA in obese patients. The present review questions the
      common perception that obesity unacceptably increases the risk of sternal wound
      complications in patients receiving BIMA grafting. Moreover, the use of
      skeletonization harvesting technique is expected to further minimize such a risk.
      Our institutional experience confirmed that BIMA grafting is a safe strategy
      which does not increase operative mortality and does not significantly affect the
      incidence of sternal wound complications. On the other hand, a long term benefit
      in terms of overall survival and freedom from repeat revascularization from the
      use of BIMA was found. 

PMID- 25598216
TI  - Are two really always better than one? Results, concerns and controversies in the
      use of bilateral internal thoracic arteries for coronary artery bypass grafting
      in the elderly: a systematic review and meta-analysis.
AB  - INTRODUCTION: Bilateral internal thoracic artery grafting appears to be the
      preferred method to achieve durable long-term coronary artery revascularization.
      However, data reporting the benefit of this technique in the elderly is very
      conflicting. METHOD: We performed a systematic review of available literature
      (till November 2014) using multiple databases to identify studies comparing
      clinical events in patients undergoing coronary artery bypass grafting using
      either a single or double internal thoracic artery in the elderly. While early
      mortality was the primary end-point of inclusion, other adverse events compared
      were sternal wound infection (deep and superficial), stroke and peri-operative
      myocardial infarction. Individual and pooled odd's ratios were calculated using
      the Mantel-Haenzel method (random effect model); sensitivity analysis was
      performed. Results are presented using 95% confidence intervals. RESULT: Nine
      retrospective studies (4479 BITA, 7733 LITA patients) fulfilled search criteria.
      Deep sternal wound infection was significantly higher after BITA harvest [OR 1.86
      (1.3-2.5); I(2) = 0%; p < 0.01]. Early mortality (BITA 3.6% vs SITA 3.1%; p =
      0.86), stroke [OR 0.7(0.4-1.1); p = 0.1], and peri-operative myocardial
      infarction (BITA 4.3% vs SITA 2.3%; p = 0.1) were comparable in both cohorts.
      Long-term survival favored the BITA cohort in two propensity matched studies.
      CONCLUSION: The incidence of deep sternal wound infection may be significantly
      higher after the harvest of both internal thoracic arteries in the elderly. While
      other post-operative adverse events are comparable, data regarding the long-term
      survival advantage in this cohort is conflicting. Hence, the use of both internal
      thoracic arteries in this age group needs to be invidualized.

PMID- 25598220
TI  - Progressive muscular atrophy: a patient with confirmatory postmortem findings.

PMID- 25598219
TI  - 3-T magnetic resonance imaging simultaneous automated multimodal approach
      improves detection of ambiguous visual hippocampal sclerosis.
AB  - BACKGROUND AND PURPOSE: To evaluate if an automatic magnetic resonance imaging
      (MRI) processing system may improve detection of hippocampal sclerosis (Hs) in
      patients with mesial temporal lobe epilepsy (MTLE). METHODS: Eighty consecutive
      patients with a diagnosis of MTLE and 20 age- and sex-matched controls were
      prospectively recruited and included in our study. The entire group had 3-T MRI
      visual assessment of Hs analysed by two blinded imaging epilepsy experts.
      Logistic regression was used to evaluate the performances of neuroradiologists
      and multimodal analysis. RESULTS: The multimodal automated tool gave no evidence
      of Hs in all 20 controls and classified the 80 MTLE patients as follows: normal
      MRI (54/80), left Hs (14/80), right Hs (11/80) and bilateral Hs (1/80). Of note,
      this multimodal automated tool was always concordant with the side of MTLE, as
      determined by a comprehensive electroclinical evaluation. In comparison with
      standard visual assessment, the multimodal automated tool resolved five ambiguous
      cases, being able to lateralize Hs in four patients and detecting one case of
      bilateral Hs. Moreover, comparing the performances of the three logistic
      regression models, the multimodal approach overcame performances obtained with a
      single image modality for both the hemispheres, reaching a global accuracy value
      of 0.97 for the right and 0.98 for the left hemisphere. CONCLUSIONS: Multimodal
      quantitative automated MRI is a reliable and useful tool to depict and lateralize
      Hs in patients with MTLE, and may help to lateralize the side of MTLE especially
      in subtle and uncertain cases.

PMID- 25598218
TI  - Prevalent and distinct spliceosomal 3'-end processing mechanisms for fungal
      telomerase RNA.
AB  - Telomerase RNA (TER) is an essential component of the telomerase
      ribonucleoprotein complex. The mechanism for TER 3'-end processing is highly
      divergent among different organisms. Here we report a unique spliceosome-mediated
      TER 3'-end cleavage mechanism in Neurospora crassa that is distinct from that
      found specifically in the fission yeast Schizosaccharomyces pombe. While the S.
      pombe TER intron contains the canonical 5'-splice site GUAUGU, the N. crassa TER
      intron contains a non-canonical 5'-splice site AUAAGU that alone prevents the
      second step of splicing and promotes spliceosomal cleavage. The unique N. crassa
      TER 5'-splice site sequence is evolutionarily conserved in TERs from
      Pezizomycotina and early branching Taphrinomycotina species. This suggests that
      the widespread and basal N. crassa-type spliceosomal cleavage mechanism is more
      ancestral than the S. pombe-type. The discovery of a prevalent, yet distinct,
      spliceosomal cleavage mechanism throughout diverse fungal clades furthers our
      understanding of TER evolution and non-coding RNA processing. 

PMID- 25598221
TI  - Dynamic arterial elastance predicts mean arterial pressure decrease associated
      with decreasing norepinephrine dosage in septic shock.
AB  - INTRODUCTION: Gradual reduction of the dosage of norepinephrine (NE) in patients
      with septic shock is usually left to the physician's discretion. No hemodynamic
      indicator predictive of the possibility of decreasing the NE dosage is currently
      available at the bedside. The respiratory pulse pressure variation/respiratory
      stroke volume variation (dynamic arterial elastance (Eadyn)) ratio has been
      proposed as an indicator of vascular tone. The purpose of this study was to
      determine whether Eadyn can be used to predict the decrease in arterial pressure
      when decreasing the NE dosage in resuscitated sepsis patients. METHODS: A
      prospective study was carried out in a university hospital intensive care unit.
      All consecutive patients with septic shock monitored by PICCO2 for whom the
      intensive care physician planned to decrease the NE dosage were enrolled.
      Measurements of hemodynamic and PICCO2 variables were obtained before/after
      decreasing the NE dosage. Responders were defined by a >15% decrease in mean
      arterial pressure (MAP). RESULTS: In total, 35 patients were included. MAP
      decreased by >15% after decreasing the NE dosage in 37% of patients (n = 13).
      Clinical characteristics appeared to be similar between responders and
      nonresponders. Eadyn was lower in responders than in nonresponders (0.75 (0.69 to
      0.85) versus 1 (0. 83 to 1.22), P <0.05). Baseline Eadyn was correlated with NE
      induced MAP variations (r = 0.47, P = 0.005). An Eadyn less than 0.94 predicted a
      decrease in arterial pressure, with an area under the receiver-operating
      characteristic curve of 0.87 (95% confidence interval (95% CI): 0.72 to 0.96; P
      <0.0001), 100% sensitivity, and 68% specificity. CONCLUSIONS: In sepsis patients
      treated with NE, Eadyn may predict the decrease in arterial pressure in response
      to NE dose reduction. Eadyn may constitute an easy-to-use functional approach to
      arterial-tone assessment, which may be helpful to identify patients likely to
      benefit from NE dose reduction.

PMID- 25598217
TI  - The role of the cell-cell interactions in cancer progression.
AB  - In the field of cancer research, scientific investigations are based on analysing
      differences in the secretome, the proteome, the transcriptome, the expression of
      cell surface molecules, and the deregulation of signal transduction pathways
      between neoplastic and normal cells. Accumulating evidence indicates a crucial
      role in carcinogenesis concerning not only stromal cells but also normal cells
      from target organs and tissue where tumours emerge. The tumour microenvironment
      (TME) definitively plays an important role in regulating neighbouring cell
      behaviour. To date, limited attention has been focused upon interactions between
      cancer cells and normal cells. This review concentrates on the interactions
      between stromal and healthy cells from the TME in cancer development. In the
      article, the authors also describe mutations, genes and proteins expression
      pattern that are involved in tumour development in target organ. 

PMID- 25598224
TI  - nNOS is involved in cardiac remodeling induced by chronic ethanol consumption.
AB  - Chronic ethanol consumption has deleterious effects on the cardiovascular system
      by directly damaging the myocardial structure and/or by neurohormonal activation.
      Moreover, nitric oxide (NO) derived from neuronal NO synthase (nNOS) seems to be
      important to balance the harmful effects of ethanol consumption, because it
      influences several aspects of cardiac physiology and attenuates pathological
      cardiac remodeling. However, the impact of chronic ethanol consumption on nNOS
      expression is unknown. We address this subject in the present study by evaluating
      whether chronic ethanol consumption induces cardiac remodeling and hypertension,
      and if these changes are associated with alterations in the expression of nNOS.
      Male Wistar rats were examined after ingesting a 20% alcohol solution for 6
      months. Blood alcohol concentration and brain natriuretic peptide (BNP) levels
      were measured. The cardiac remodeling was assessed by histomorphometric analysis
      and the nNOS expression was evaluated by immunofluorescence and western blot
      analysis. Our results show that chronic ethanol consumption induces cardiac
      remodeling, namely thinning of left ventricular wall, cardiomyocyte hypertrophy
      and increased fibrosis, and elevations of arterial blood pressure. They also show
      that in rats fed with ethanol for 6 months, the circulating BNP levels had
      decreased as well as the expression of nNOS in left ventricle cardiomyocytes.
      These findings suggest that the effects of chronic ethanol consumption on BNP
      levels and/or on nNOS expression in cardiomyocytes may contribute to aggravate
      the cardiac remodeling and leads to progression of cardiomyopathy. 

PMID- 25598226
TI  - Gaining acceptance for the use of in vitro toxicity assays and QIVIVE in
      regulatory risk assessment.
AB  - Testing strategies are anticipated to increasingly rely on in vitro data as a
      basis to characterize early steps or key events in toxicity at relevant dose
      levels in human tissues. Such strategies require quantitative in vitro to in vivo
      extrapolation to characterize dose-response as a basis for comparison with
      exposure to estimate risk. Current experience in the incorporation of mechanistic
      and in vitro data in risk assessment is considered here in the context of
      identified principles to increase the potential for timely acceptance of more
      progressive and tailored testing strategies by the regulatory community. These
      principles are outlined as transitioning in a familiar context, tiering to
      acquire experience and increase confidence, contextual knowledge transfer to
      facilitate interpretation and communication, coordination and development of
      expertise and continuing challenge. A proposed pragmatic tiered data driven
      framework which includes increasing reliance on in vitro data and quantitative in
      vitro to in vivo extrapolation is considered in the context of these principles.
      Based on this analysis, possible additional steps that might facilitate timely
      evolution and potentially, uptake are identified. 

PMID- 25598223
TI  - Enriched environment inhibits mouse pancreatic cancer growth and down-regulates
      the expression of mitochondria-related genes in cancer cells.
AB  - Psycho-social stress has been suggested to influence the development of cancer,
      but it remains poorly defined with regard to pancreatic cancer, a lethal
      malignancy with few effective treatment modalities. In this study, we sought to
      investigate the impacts of enriched environment (EE) housing, a rodent model of
      "eustress", on the growth of mouse pancreatic cancer, and to explore the
      potential underlying mechanisms through gene expression profiling. The EE mice
      showed significantly reduced tumor weights in both subcutaneous (53%) and
      orthotopic (41%) models, while each single component of EE (inanimate
      stimulation, social stimulation or physical exercise) was not profound enough to
      achieve comparative anti-tumor effects as EE. The integrative transcriptomic and
      proteomic analysis revealed that in response to EE, a total of 129 genes in the
      tumors showed differential expression at both the mRNA and protein levels. The
      differentially expressed genes were mostly localized to the mitochondria and
      enriched in the citrate cycle and oxidative phosphorylation pathways.
      Interestingly, nearly all of the mitochondria-related genes were down-regulated
      by EE. Our data have provided experimental evidence in favor of the application
      of positive stress or of benign environmental stimulation in pancreatic cancer
      therapy. 

PMID- 25598225
TI  - Toxicoproteomic analysis of pulmonary carbon nanotube exposure using LC-MS/MS.
AB  - Toxicoproteomics is a developing field that utilizes global proteomic
      methodologies to investigate the physiological response as a result of adverse
      toxicant exposure. The aim of this study was to compare the protein secretion
      profile in lung bronchoalveolar lavage fluid (BALF) from mice exposed to non
      functionalized multi-walled carbon nanotubes (U-MWCNTs) or MWCNTs functionalized
      by nanoscale Al2O3 coatings (A-MWCNT) formed using atomic layer deposition (ALD).
      Proteins were identified using liquid chromatography tandem mass spectrometry (LC
      MS/MS), and quantified using a combination of two label-free proteomic methods:
      spectral counting and MS1 peak area analysis. On average 465 protein groups were
      identified per sample and proteins were first screened using spectral counting
      and the Fisher's exact test to determine differentially regulated species.
      Significant proteins by Fisher's exact test (p<0.05) were then verified by
      integrating the intensity under the extracted ion chromatogram from a single
      unique peptide for each protein across all runs. A two sample t-test based on
      integrated peak intensities discovered differences in 27 proteins for control
      versus U-MWCNT, 13 proteins for control versus A-MWCNT, and 2 proteins for U
      MWCNT versus A-MWCNT. Finally, an in-vitro binding experiment was performed
      yielding 4 common proteins statistically different (p<0.05) for both the in-vitro
      and in-vivo study. Several of the proteins found to be significantly different
      between exposed and control groups are known to play a key role in inflammatory
      and immune response. A comparison between the in-vitro and in-vivo CNT exposure
      emphasized a true biological response to CNT exposure. 

PMID- 25598228
TI  - The role of myosin-II in force generation of DRG filopodia and lamellipodia.
AB  - Differentiating neurons process the mechanical stimulus by exerting the
      protrusive forces through lamellipodia and filopodia. We used optical tweezers,
      video imaging and immunocytochemistry to analyze the role of non-muscle myosin-II
      on the protrusive force exerted by lamellipodia and filopodia from developing
      growth cones (GCs) of isolated Dorsal Root Ganglia (DRG) neurons. When the
      activity of myosin-II was inhibited by 30 MUM Blebbistatin protrusion/retraction
      cycles of lamellipodia slowed down and during retraction lamellipodia could not
      lift up axially as in control condition. Inhibition of actin polymerization with
      25 nM Cytochalasin-D and of microtubule polymerization with 500 nM Nocodazole
      slowed down the protrusion/retraction cycles, but only Cytochalasin-D decreased
      lamellipodia axial motion. The force exerted by lamellipodia treated with
      Blebbistatin decreased by 50%, but, surprisingly, the force exerted by filopodia
      increased by 20-50%. The concomitant disruption of microtubules caused by
      Nocodazole abolished the increase of the force exerted by filopodia treated with
      Blebbistatin. These results suggest that; i- Myosin-II controls the force exerted
      by lamellipodia and filopodia; ii- contractions of the actomyosin complex formed
      by filaments of actin and myosin have an active role in ruffle formation; iii-
      myosin-II is an essential component of the structural stability of GCs
      architecture.

PMID- 25598227
TI  - Detection of malignant mesothelioma using nuclear structure of mesothelial cells
      in effusion cytology specimens.
AB  - Mesothelioma is a form of cancer generally caused from previous exposure to
      asbestos. Although it was considered a rare neoplasm in the past, its incidence
      is increasing worldwide due to extensive use of asbestos. In the current practice
      of medicine, the gold standard for diagnosing mesothelioma is through a pleural
      biopsy with subsequent histologic examination of the tissue. The diagnostic
      tissue should demonstrate the invasion by the tumor and is obtained through
      thoracoscopy or open thoracotomy, both being highly invasive surgical operations.
      On the other hand, thoracocentesis, which is removal of effusion fluid from the
      pleural space, is a far less invasive procedure that can provide material for
      cytological examination. In this study, we aim at detecting and classifying
      malignant mesothelioma based on the nuclear chromatin distribution from digital
      images of mesothelial cells in effusion cytology specimens. Accordingly, a
      computerized method is developed to determine whether a set of nuclei belonging
      to a patient is benign or malignant. The quantification of chromatin distribution
      is performed by using the optimal transport-based linear embedding for segmented
      nuclei in combination with the modified Fisher discriminant analysis.
      Classification is then performed through a k-nearest neighborhood approach and a
      basic voting strategy. Our experiments on 34 different human cases result in 100%
      accurate predictions computed with blind cross validation. Experimental
      comparisons also show that the new method can significantly outperform standard
      numerical feature-type methods in terms of agreement with the clinical diagnosis
      gold standard. According to our results, we conclude that nuclear structure of
      mesothelial cells alone may contain enough information to separate malignant
      mesothelioma from benign mesothelial proliferations.

PMID- 25598231
TI  - An unusual cause of bowel obstruction from a feeding jejunostomy.

PMID- 25598229
TI  - Quantification of plasma microRNAs in a group of healthy smokers, ex-smokers and
      non-smokers and correlation to biomarkers of tobacco exposure.
AB  - The stability of circulating miRNAs, their non-invasive sampling techniques and
      deregulation in diseases make them potential candidate biomarkers of biological
      effect. Here, we profiled the level of 84 plasma miRNAs in 30 smokers, 20 non
      smokers and 20 ex-smokers. A robust statistical strategy was applied with
      replicate samples to account for reproducibility of the results. We identified
      differential expression of miR-124 and let-7a between the smoking and control
      groups. We further explored the dose-response relationship of miR-124 and let-7a
      with two biomarkers of tobacco exposure and found that this relationship was
      affected by adjustments based on age, pack-year and gender. 

PMID- 25598232
TI  - Ligand-promoted ortho-C-H amination with Pd catalysts.
AB  - 2,4,6-Trimethoxypyridine is identified as an efficient ligand for promoting a Pd
      catalyzed ortho-C-H amination of both benzamides and triflyl-protected
      benzylamines. This finding provides guidance for the development of ligands that
      can improve or enable Pd(II)-catalyzed Csp2-H activation reactions directed by
      weakly coordinating functional groups.

PMID- 25598230
TI  - Effects of the novel BK (KCa 1.1) channel opener GoSlo-SR-5-130 are dependent on
      the presence of BKbeta subunits.
AB  - BACKGROUND AND PURPOSE: GoSlo-SR compounds are efficacious BK (KCa 1.1) channel
      openers, but little is known about their mechanism of action or effect on bladder
      contractility. We examined the effects of two closely related compounds on BK
      currents and bladder contractions. EXPERIMENTAL APPROACH: A combination of
      electrophysiology, molecular biology and synthetic chemistry was used to examine
      the effects of two novel channel agonists on BK channels from bladder smooth
      muscle cells and in HEK cells expressing BKalpha alone or in combination with
      either beta1 or beta4 subunits. KEY RESULTS: GoSlo-SR-5-6 shifted the voltage
      required for half maximal activation (V1/2 ) of BK channels approximately -100
      mV, irrespective of the presence of regulatory beta subunits. The deaminated
      derivative, GoSlo-SR-5-130, also shifted the activation V1/2 in smooth muscle
      cells by approximately -100 mV; however, this was reduced by ~80% in HEK cells
      expressing only BKalpha subunits. When beta1 or beta4 subunits were co-expressed
      with BKalpha, efficacy was restored. GoSlo-SR-5-130 caused a concentration
      dependent reduction in spontaneous bladder contraction amplitude and this was
      abolished by iberiotoxin, consistent with an effect on BK channels. CONCLUSIONS
      AND IMPLICATIONS: GoSlo-SR-5-130 required beta1 or beta4 subunits to mediate its
      full effects, whereas GoSlo-SR-5-6 worked equally well in the absence or presence
      of beta subunits. GoSlo-SR-5-130 inhibited spontaneous bladder contractions by
      activating BK channels. The novel BK channel opener, GoSlo-SR-5-130, is
      approximately fivefold more efficacious on BK channels with regulatory beta
      subunits and may be a useful scaffold in the development of drugs to treat
      diseases such as overactive bladder.

PMID- 25598234
TI  - Effect of resistance training using bodyweight in the elderly: Comparison of
      resistance exercise movement between slow and normal speed movement.
AB  - AIM: The present study investigated whether a slow movement protocol can be
      applied to resistance training using bodyweight. In addition, the intervention
      program combined plyometric exercise with resistance exercise to improve physical
      function overall. METHODS: A total of 39 active elderly adults participated in a
      16-week intervention. The program consisted of five resistance exercises and four
      plyometric exercises using their own bodyweight with a single set for each
      exercise. Participants were assigned to one of two experimental groups. One group
      carried out resistance exercise with slow movement and tonic force generation (3
      s concentric, 3-s eccentric and 1-s isometric actions with no rest between each
      repetition). The other group as a movement comparison followed the same regimen,
      but at normal speed (1-s eccentric and 1-s concentric actions with 1-s rest
      between each repetition). Muscle size, strength and physical function were
      measured before and after the intervention period. RESULTS: After the
      intervention, strengths of upper and lower limbs, and maximum leg extensor power
      were significantly improved in both groups. Muscle size did not change in either
      group. There were no significant differences in any of the parameters between
      groups. CONCLUSIONS: The intervention program using only own bodyweight that
      comprised resistance exercise with slow movement and plyometric exercise can
      improve physical function in the elderly, even with single sets for each
      exercise. However, there was no enhanced muscle hypertrophic effect. Further
      attempts, such as increasing performing multiple sets, would be required to
      induce muscle hypertrophy. Geriatr Gerontol Int 2015; 15: 1270-1277.

PMID- 25598235
TI  - Is apical periodontitis in root filled teeth associated with the type of
      restoration?
AB  - OBJECTIVE: To study the association between type of restoration and apical
      periodontitis (AP) in root filled teeth. MATERIALS AND METHODS: The present study
      used data from surveys conducted in 1983, 1993 and 2003. In 1983, 130 randomly
      selected subjects aged 3-80 years in the city of Jonkoping, Sweden, were invited
      for a clinical and radiological examination. The study was repeated in 1993 and
      2003. New participants were, thus, recruited with the same sampling criteria and
      sample size in the same geographical area in 1993 and 2003, respectively. In the
      present study, only dentate individuals aged 20-70 years with >=1 root filled
      tooth were included, yielding a sample of 788 subjects with 2634 root filled
      teeth. Apical periodontitis on the tooth level was the dependent variable.
      Periapical status was assessed according to Periapical Index (PAI). Independent
      variables were root filling quality, recurrent caries, type of restoration,
      number of teeth with apical periodontitis, age and gender. Root fillings
      appearing homogenous and ending within 2 mm from radiographic apex were regarded
      as adequate, otherwise inadequate. All radiographs were re-studied by one
      observer regarding periapical status and root filling quality. Risk was analyzed
      by means of a GEE model. RESULTS: Type of restoration, root filling quality,
      number of teeth with apical periodontitis within the individual and age were
      found to be predictors of AP in root filled teeth. Presence of recurrent caries
      and gender were not found to be associated with AP. CONCLUSIONS: According to the
      present study, root filling quality and type of restoration may be predictive of
      AP in root filled teeth.

PMID- 25598233
TI  - Translating new developments in eosinophilic esophagitis pathogenesis into
      clinical practice.
AB  - OPINION STATEMENT: New developments in eosinophilic esophagitis (EoE)
      pathogenesis are shaping our current therapeutic and management strategies. EoE
      is a chronic allergic inflammatory disease with progression to fibrostenotic
      disease. The disease warrants early diagnosis and long-term maintenance therapy.
      The diagnosis of EoE should be based on the concept of an allergy-mediated
      disease with esophageal dysfunction and esophageal eosinophilia. Recent findings
      suggest that proton pump inhibitor (PPI)-responsive esophageal eosinophilia (PPI
      REE) is likely a continuum of EoE or a similar T-helper 2 (Th2)-mediated allergic
      process. PPIs have therapeutic properties that can benefit both gastroesophageal
      reflux disease (GERD) and EoE. Therefore, PPIs should be considered not a
      diagnostic tool but, rather, a therapeutic option for EoE. If patients are PPI
      nonresponsive, then dietary therapy or steroid therapy should be considered.
      Dilation can be reserved as adjuvant therapy for severe fibrostenotic lesions.

PMID- 25598237
TI  - Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney
      injury in preterm newborns.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be
      a highly sensitive and specific marker of acute kidney injury (AKI). The aim of
      this study was to assess the factors affecting serum and urine total NGAL in
      preterm newborns, limiting the role of this new potential marker of AKI. METHODS:
      Serum and urinary total NGAL concentrations were determined in 57 preterm infants
      admitted to the Neonatal Intensive Care Unit in the following points of time:
      first week of life, between 8 and 14 days of life, and after the fourth week of
      life. Patients' clinical conditions were evaluated based on NTISS (Neonatal
      Therapeutic Intervention Scoring System). Two gestational age subgroups were
      distinguished: <=29 and 30 to 35 weeks of gestation. We sought correlation
      between total NGAL values and gestational age, birth weight, Apgar score and
      severity of clinical condition, with particular interest in inflammatory status.
      RESULTS: Serum and urinary total NGAL concentration correlated with inflammatory
      markers, such as CRP and procalcitonin, as well as with NTISS values. Birth
      weight and gestational age influence urinary NGAL (uNGAL) values in the first two
      weeks of life. In AKI (N = 8) patients uNGAL values were significantly higher
      than in non-AKI newborns. CONCLUSIONS: We conclude that inflammatory status and
      prematurity limits the specificity of total NGAL measurement as a marker of AKI.

PMID- 25598236
TI  - Renoprotective effect of berberine via intonation on apoptosis and mitochondrial
      dependent pathway in renal ischemia reperfusion-induced mutilation.
AB  - Ischemic acute renal failure is a condition that extends subsequent to sudden and
      momentary fall in overall or regional blood flow to the kidney. The present
      investigation was deliberated to scrutinize the renoprotective potential of
      berberine in animal model of renal ischemia reperfusion (RIR) induced dent via
      assessment of various biochemical and molecular biomarkers. Male Wistar rats were
      anesthetized and the right kidney was removed through a small flank incision.
      Renal ischemia reperfusion was persuaded in uni-nephrectomized rats by occlusion
      of left renal artery for 45 min and reperfusion for 4 weeks. After 4 weeks of
      treatment of berberine (10, 20, and 40 mg/kg, p.o.), hemodynamic and left
      ventricular function were evaluated. Induction of ischemia reperfusion resulted
      callous mutilation in kidney which was confirmed by alterations in oxidative
      stress (SOD, GSH, and MDA), membrane bound enzymes, kidney function markers
      (serum creatinine and BUN), and mitochondrial dysfunction. Moreover, RIR injury
      exhibited incredible alterations in mRNA expression of KIM-1, NGAL, Caspase-3,
      Bax, Bcl-2, and TNF-alpha levels. Conversely treatment of berberine (20 and 40
      mg/kg) significantly (p < 0.01 and p < 0.001) restored ischemia reperfusion
      induced marring via intonation of biochemical and molecular biomarkers. To sum
      up, berberine demonstrated compelling renoprotective effect in RIR injury via
      caspase-mitochondria-dependent pathway.

PMID- 25598238
TI  - Comparison of renal function after donor and radical nephrectomy.
AB  - Glomerular filtration rate (GFR) is directly proportionate to nephron reserves.
      In this respect, it is known that the patients who underwent radical nephrectomy
      due to renal tumor are under high risk of chronic kidney disease (CKD) in the
      long term. In this study, it was aimed to compare post-operative renal functions
      of patients who underwent radical nephrectomy due to renal malignancy and who
      underwent donor nephrectomy as renal donors, to observe whether renal failure
      process develops or not, and to determine the factors that affect post-operative
      renal functions. 70 patients who underwent donor nephrectomy as renal donors and
      130 patients who underwent radical nephrectomy due to renal tumor were studied.
      When we divided the groups as those with a GFR of below 60 mL/min/1.73 m(2) and
      those with a GFR of above 60 mL/min/1.73 m(2), we observed that GFR values of
      patients who underwent radical nephrectomy had a significantly stronger tendency
      to stay below 60 mL/min/1.73 m(2) compared to patients who underwent donor
      nephrectomy (p < 0.001). When we divided the groups as those with a GFR of below
      30 mL/min/1.73 m(2) and those with a GFR of above 30 mL/min/1.73 m(2), we
      observed that there were no patients in donor nephrectomy group whose GFR values
      dropped below 30 mL/min/1.73 m(2) and there was not a statistically significant
      difference between the groups (p = 0.099). If possible, nephron sparing methods
      should be preferred for patients to undergo nephrectomy because of the tumor
      without ignoring oncologic results and it should be remembered that patient's age
      and pre-operative renal functions may affect post-operative results in donor
      selection.

PMID- 25598239
TI  - Evaluation of children with steroid-sensitive nephrotic syndrome in terms of
      allergies.
AB  - BACKGROUND: The etiology of minimal-change disease is not fully known, it is
      believed to be mediated by the immune system. Minimal-change disease also
      reported as having association with atopy. In this study, atopy history, the
      levels of serum IgE, and skin prick test in children with steroid-sensitive
      nephrotic syndrome were investigated. METHODS: A group of 30 children (mean age
      7.7 +/- 2.2 years, 56.6% male) diagnosed with steroid-sensitive nephrotic
      syndrome were included in the study. Serum immunoglobulin E levels and eosinophil
      counts were evaluated in children with steroid-sensitive nephrotic syndrome both
      in relapse and remission. Skin prick test was performed in remission. RESULTS: Of
      the 30 children investigated, 11 (36.7%) had a history of atopy. The median serum
      total IgE levels in nephrotic children in relapse, with (445 IU/mL) and without
      atopy (310 IU/mL) were significantly higher than those in remission
      (respectively, 200 IU/mL, p = 0.021, and 42 IU/mL, p = 0.001). The skin prick
      tests for all the allergens were evaluated as negative in all the patients.
      CONCLUSION: It was thought that increased IgE may reflect the activation of
      immune mechanism following various stimuli rather than a direct association with
      atopy in children with steroid-sensitive nephrotic syndrome.

PMID- 25598240
TI  - Evaluation of cardiac involvement in caucasian patients with skin sarcoidosis.

PMID- 25598243
TI  - Spatially distributed current oscillations with electrochemical reactions in
      microfluidic flow cells.
AB  - The formation of spatiotemporal patterns is investigated by using a chemical
      reaction on the surface of a high-aspect-ratio metal electrode positioned in a
      flow channel. A partial differential equation model is formulated for nickel
      dissolution in sulfuric acid in a microfluidic flow channel. The model
      simulations predict oscillatory patterns that are spatially distributed on the
      electrode surface; the downstream portion of the metal surface exhibits large
      amplitude, nonlinear oscillations of dissolution rates, whereas the upstream
      portion displays small-amplitude, harmonic oscillations with a phase delay. The
      features of the dynamical response can be interpreted by the dependence of local
      dynamics on the widely varying surface conditions and the presence of strong
      coupling. The patterns can be observed for both contiguous and segmented metal
      surfaces. The existence of spatially distributed current oscillations is
      confirmed in experiments with Ni electrodissolution in a microfluidic device. The
      results show the impact of a widely heterogeneous environment on the types of
      patterns of chemical reaction rates. 

PMID- 25598242
TI  - Metagenomic insights into the effects of fructo-oligosaccharides (FOS) on the
      composition of fecal microbiota in mice.
AB  - Fructo-oligosaccharides (FOS) are usually regarded as a type of prebiotic,
      favorably stimulating the growth of bifidobacteria and lactobacilli. However,
      they are not the specific substrates for these target species, and other
      bacteria, such as Streptococcus, Escherichia, and Clostridium, have been shown to
      be able to utilize FOS. Previous studies have mainly investigated only a few
      bacteria groups, and few reports analyzed the global effects of FOS on intestinal
      microbial communities. In this study the effects of FOS on gut bacteria in mice
      were investigated through a 16S rRNA metagenomic analysis. In the FOS-low group,
      the abundance of Actinobacteria significantly increased and that of Bacteroidetes
      decreased after FOS diet (5%) for 3 weeks. In the FOS-high group, Enterococcus
      was promoted and levels of Bifidobacterium and Olsenella both notably increased
      after FOS diet (25%) and the microbiota tended to revert to initial structure 2
      weeks after FOS treatment ceased. The most striking observation was that
      Olsenella became a dominant genus comparable with Bifidobacterium after FOS
      treatment, and one strain of Olsenella, isolated from mice feces, was confirmed,
      for the first time, to be capable of using FOS. The results indicated that
      metagenomic analysis was helpful to reveal the FOS effects on the global
      composition of gut communities and new target for future studies. 

PMID- 25598244
TI  - [Surveillance and control of risk factors: the key to the chronic non
      communicable disease control and prevalence among floating population].

PMID- 25598241
TI  - Cyanide enhances hydrogen peroxide toxicity by recruiting endogenous iron to
      trigger catastrophic chromosomal fragmentation.
AB  - Hydrogen peroxide (HP) or cyanide (CN) are bacteriostatic at low-millimolar
      concentrations for growing Escherichia coli, whereas CN + HP mixture is strongly
      bactericidal. We show that this synergistic toxicity is associated with
      catastrophic chromosomal fragmentation. Since CN alone does not kill at any
      concentration, while HP alone kills at 20 mM, CN must potentiate HP poisoning.
      The CN + HP killing is blocked by iron chelators, suggesting Fenton's reaction.
      Indeed, we show that CN enhances plasmid DNA relaxation due to Fenton's reaction
      in vitro. However, mutants with elevated iron or HP pools are not acutely
      sensitive to HP-alone treatment, suggesting that, in addition, in vivo CN
      recruits iron from intracellular depots. We found that part of the CN-recruited
      iron pool is managed by ferritin and Dps: ferritin releases iron on cue from CN,
      while Dps sequesters it, quelling Fenton's reaction. We propose that disrupting
      intracellular iron trafficking is a common strategy employed by the immune system
      to kill microbes. 

PMID- 25598245
TI  - [Drinking behaviors and patterns among floating population aged 18-59 years old
      in China, 2012].
AB  - OBJECTIVE: To understand the drinking behaviors and patterns among floating
      population in China. METHODS: Floating population were selected through
      multistage clustering sampling method, stratified by 6 major industries in 170
      counties and districts from 31 provinces/autonomous regions, and Xinjiang
      Construction Corps, in mainland China. Design-based methods were adopted to
      analyze the drinking behavior in subpopulations. RESULTS: A total of 48 697
      floating population aged 18-59 years were included in the study. The overall
      prevalence rate of drinking was 51.7% with 71.9% in men and 24.7% in women, in
      the last 12 months. Among those who ever drank, the weekly drinking prevalence
      and daily alcohol intake were 53.9% and 18.7 g in males while 16.7% and 4.1 g in
      females, respectively, among those floating population. Weekly drinking
      prevalence rates, for both genders, increased along with the increase of age (P <
      0.01), but declining with having higher education level (P < 0.01). Among male
      drinkers, daily alcohol intake increased with age(P < 0.01) but declining with
      those having higher education (P < 0.01). Prevalence rates on excessive drinking,
      hazardous drinking and harmful drinking among male drinkers were 23.6% , 6.6% and
      6.9%, respectively, but among female drinkers the figures were 6.3% , 2.3% and
      1.5% , respectively. More male and older drinkers had excessive drinking,
      hazardous drinking or harmful drinking than the younger drinkers (P < 0.01),
      while less male drinkers in those having lower education (P < 0.01). 71.2% male
      and 33.1% female drinkers experienced at least once binge drinking in the last 12
      months. Distribution of binge drinking frequencies were statistically different
      among male drinkers by age groups, education levels, or occupation they engaged
      in (P < 0.01). Among all the 6 occupations, floating population from the
      construction industry had the highest prevalence rates on items as weekly
      drinking, daily alcohol intake and prevalence of unhealthy drinking behaviors,
      except for hazardous drinking behaviors. CONCLUSION: Drinking behavior was
      prevalent among floating population in China. Significant difference was seen
      between genders. Unhealthy drinking behaviors varied greatly among male drinkers
      at different age groups or education levels as well as among those working in the
      different industries.

PMID- 25598247
TI  - [Fruit and vegetables intake among the Chinese migrant population aged 18 to 59
      years old in 2012].
AB  - OBJECTIVE: To describe the intake of fruit and vegetables among employed migrant
      population aged 18 to 59 year-olds in China. METHODS: Data from the Migrant
      Population Survey related to China Chronic Disease and Risk Factor Surveillance
      that conducted in 170 counties/districts in 31 provinces, 2012, was used.
      Information on non-communicable diseases and related risk factors among migrant
      population were collected through face-to-face questionnaire interview, physical
      measurement and lab tests. A total of 48 704 subjects aged 18 to 59 years old
      were included in our study. Sample was standardized by age and sex. Information
      on average daily fruit and vegetables intake, prevalence of low fruit and
      vegetables intake, grouped by sex, age, industries, and education level were
      analyzed. RESULTS: The average daily intakes of vegetables and fruits were 353.7
      (95%CI:351.3-356.2) g and 125.1 (95%CI:123.4-126.9) g respectively, among the
      employed migrant population aged 18-59 years old in China. Prevalence of low
      fruit and vegetables intake was 44.1% (95% CI:43.5%-44.6% ) among employed
      migrant population, 46.2% (95% CI: 45.5%-47.0%)for males and 41.2% (95% CI:40.3%
      42.0%)for females (chi(2) = 82.19, P < 0.05). Among different professions, the
      prevalence of low fruit and vegetables intake was the highest among people
      working in accommodation and restaurants (46.2%, 95%CI:45.0%-47.3%) while the
      lowest seen among those working in social services (42.5%, 95%CI:41.4%
      43.7%,chi(2) = 15.81, P < 0.05). The prevalence of low fruit and vegetables
      intake showed a decrease along with the increase of education levels (chi(2) =
      22.29, P < 0.05). CONCLUSION: In 2012, more than 40% of the employed migrant
      population aged 18 to 59 years old in China had low fruit and vegetables intake.
      Being male and with low education level were risk factors linked with the higher
      prevalence of low fruit and vegetables intake.

PMID- 25598246
TI  - [Smoking behavior among the Chinese employed floating population aged 18-59 in
      2012].
AB  - OBJECTIVE: To understand the prevalence of cigarette smoking among employed
      floating population in China and to provide evidence for developing prevention
      and control measures targeted at cigarette smoking among them. METHODS: On the
      basis of the Disease Surveillance Points (DSPs)System and employed distribution
      among floating population, the China Non- communicable and Chronic Disease Risk
      Factor Surveillance in 2012 sampled from 170 DSPs, multi-stage stratified equal
      sized cluster sampling method was used and stratified by six occupational groups.
      Cigarette smoking related information among the employed floating population was
      collected by face-to-face interviews. The analytical method accounted for the
      complex sampling design. RESULTS: There were 48 699 subjects, aged 18-59 years
      old, eligible and included in this analysis among the surveyed employed floating
      population. Among them, the prevalence of current smoking was 32.5% (95%CI: 32.0%
      33.0%). A significantly higher percentage of men 55.3% (95%CI:54.6%
      56.0%)relative to women 1.9% (95% CI:1.7%-2.1%)reported current smoking(chi(2) =
      2.6, P = 0.103 7). Among men, differences in current smoking rates remained
      similar across age groups (chi(2) = 2.6, P = 0.103 7), but the current smoking
      rate tended to be lower with higher education(chi(2) = 140.7, P < 0.000 1). The
      current smoking rate in men was the highest(58.6% , 95% CI:57.3%-60.0%)in the
      floating population working in the construction industry. The prevalent of daily
      cigarette smoking was 27.9% (95% CI: 27.4%-28.4%), with a significantly higher
      proportion among men 47.8% (95% CI:47.1%-48.5%) than among women 1.3% (95%CI:1.1%
      1.4%). Among daily smokers, the mean number of cigarettes smoked was
      15.6(95%CI:15.5-15.8)per day(men:15.7 per day; women: 10.3 per day). The number
      was higher in men 15.7(95% CI:15.6-15.9)than in women 10.3(95% CI:9.3-11.3).
      Among daily smoking men, the daily consumed cigarettes number increased with the
      age increased (t = 34.89, P < 0.000 1), whereas the daily consumed cigarettes
      number decreased with the increase of education level (t = -14.63, P < 0.000 1).
      The daily consumed cigarettes number in men was the highest (18.2, 95%CI:17.9
      18.6)in the floating population working in the construction industry. There were
      47.1% of the daily smokers who smoked more than 20 cigarettes per day in the
      floating population aged 18-59, with a higher percentage among men (47.6%) than
      women (21.9%). The percentage in men increased with age and education level and
      the heavy smoking rate was the highest in the construction industry (60.4%).
      Among current smokers, the percentage of attempting to quit was 10.3% (95%CI:
      9.7%-10.8%). A higher proportion of women 14.8% (95% CI:11.1%-18.5%), compared to
      men 10.1% (95% CI:9.6%-10.7%), reported attempting to quit. The rate of
      attempting to quit among current smokers increased with age. No significant
      difference in prevalence of attempting to quit by education level or occupation
      was seen. The percent of successfully quitting smoking was 6.1% (95%CI:5.7%
      6.5%). The proportion was higher in women 7.2% (95%CI:4.6%-9.8%)than in men 6.1%
      (95%CI:5.7%-6.5%). The percentage of quitting smoking successfully increased with
      age (chi(2) = 269.0, P < 0.000 1). The percent of people who exposed to
      secondhand smoking was 68.7% (95%CI: 68.1%-69.3%). The percent was higher among
      men 76.4% (95%CI:75.5%-77.3%) than in women 64.0% (95%CI:63.2%-64.9%).
      CONCLUSION: Smoking was more common among men in the employed floating population
      aged 18-59 years old, especially in the construction industry. Low percent was
      seen among those who attempting to quit, and the ones who successfully quit were
      very few.

PMID- 25598249
TI  - [Physical activities and sedentary behavior among the Chinese floating population
      aged 18-59 in 2012].
AB  - OBJECTIVE: To evaluate the prevalence of leisure-time physical activity and
      sedentary behaviors among Chinese floating population aged 18-59. METHODS: Data
      was from the Chinese Floating Population Chronic Disease Surveillance (2012). Of
      the 48 704 subjects aged 18-59 years old, information on frequency and duration
      of leisure activity was collected by face-to-face interview. Time spent on
      watching TV, reading, using computers or playing games after work was also
      calculated. RESULTS: 19.4% (95%CI:19.0%-19.7%) of the subjects took part in
      moderate or vigorous intensity physical activities at least 10 minutes for three
      days per week, with percentage higher in males than in females and increasing
      among younger males (P < 0.01). Data showed that it was opposite among females (P
      < 0.01). Physical activities increased in those with higher education for both
      males and females (P < 0.01) and showed significant differences on occupations.
      Among those who engaged in different occupations, subjects working on social
      service and manufactory presented the top two highest percentages on often
      engaging in leisure time activities and they spent 4.9 (95%CI:4.8-4.9) hours
      daily on average in sedentary behavior decreasing along with aging but increasing
      with having received higher education. CONCLUSION: The percentage of taking part
      in moderate and vigorous activities among floating population was generally low.
      Prevention should target on floating population, especially on females, those
      with lower education or at older age.

PMID- 25598248
TI  - [Red meat intake among employees of floating population aged 18-59 years old in
      China, 2012].
AB  - OBJECTIVE: To evaluate the level of daily red meat intake and prevalence of
      excessive red meat intake among employees of floating population in China.
      METHODS: 48 511 employees of floating population aged 18 to 59 from 170 counties
      of 31 provinces (autonomous regions and municipalities) and Xinjiang Production
      and Construction Corps (District) were selected by stratified cluster sampling
      method. Information on red meat intake was collected by semi-quantitative food
      frequency questionnaire. Average intake of 100 g/day, recommended by the World
      Cancer Research Fund, was used as the cut-off point to estimate the prevalence of
      excessive red meat intake. After performing the complex weighted analysis, level
      of daily red meat intake and prevalence of excessive red meat intake were
      calculated by demographic characteristics including age, education, industries
      and body mass index etc. RESULTS: 1)The mean daily red meat intake was 125.9 g
      (95%CI: 116.5 g-132.5 g), higher in men (141.6 g, 95%CI:131.3 g-148.9 g)than in
      women (104.7 g, 95%CI: 95.8 g-111.2 g) (P < 0.01). Results from the Tendency Test
      did not show statistically significant changes on the red meat intake related to
      age, education level or body mass index (P values for trend were all greater than
      0.05). The standardized mean daily intake of red meat, adjusted by 2010 census
      data of China, was 121.0 g (95% CI:113.4 g-128.7 g). 2) The prevalence of
      excessive red meat intake was 36.2% (95% CI:33.0%-39.3%) significantly higher in
      males (42.4% , 95% CI:38.9%-45.8%) than in females (27.8%, 95%CI:27.1%-31.0%) (P
      < 0.01). The prevalence was estimated to be the highest among the population aged
      30-39, with 43.5% (95%CI:39.7%-47.4%) in males and 30.1% (95%CI:26.5%-33.9%)in
      females. The standardized prevalence, adjusted by 2010 census data of China,
      appeared to be 34.6% (95%CI:31.9%-38.0%). CONCLUSION: The level of daily red meat
      intake was higher than 100 g/d, the standard recommended by the World Cancer
      Foundation, among floating population of China. Both the mean daily red meat
      intake and prevalence of excessive red meat intake were higher in floating
      population than that in the local residents in China.

PMID- 25598250
TI  - [Rate of infection and related risk factors on hepatitis C virus in three
      counties of Jiangsu province].
AB  - OBJECTIVE: To investigate the hepatitis C virus (HCV) infection rate among
      general population in Jiangsu province and to analyze the main risk factors for
      HCV infection. METHODS: Subjects in 3 counties were surveyed by stratified
      cluster random sampling in the National Major Science and Technology Projects
      demonstration area in Jiangsu province. Interview was carried out with uniformly-
      designed questionnaires. Blood samples were collected and anti-HCV tested. Data
      were analysed under SPSS 13.0. Case-control study was conducted on two groups
      with subjects under 1:4 matching by sex, age, village of residence and status of
      HCV infection. Cox's proportional hazards regression analysis was then performed
      to analyze the risk factors for HCV infection. RESULTS: The positive rate of anti
      HCV was higher in females (0.965%, 95%CI:0.899%-1.035%) than in males (0.572%,
      95%CI:0.517%-0.632%). Significant differences were noticed among the positive
      rates of anti-HCV in the three counties (0.131%, 95%CI:0.103%-0.164%;0.316%,
      95%CI: 0.268%-0.370%; 2.173% , 95% CI:2.039%-2.315% , respectively). Peak
      prevalence of anti-HCV (1.577%, 95%CI:1.425%-1.740%) was observed among persons
      at 50-59 years of age. Bottom rate (0.161%, 95%CI:0.125%-0.204%) was observed
      below 30 years of age. High anti-HCV positive rate was detected in people with
      lower education background or belonged to 'floating population'. Factors as
      having histories of hospitalization (OR = 3.049, 95% CI:1.322-7.036), blood
      transfusion (OR = 14.319, 95%CI:2.318-88.459) or sharing razor (OR = 3.604,
      95%CI:1.096-11.851) were risk factors of HCV infection in the area with the
      lowest anti-HCV positive rate. In another county, factor as having histories of
      'blood products transfusion' (OR = 7.202, 95% CI:1.170-44.310) appeared important
      while in the third county, having history of 'blood donation' (OR = 7.496,
      95%CI:6.121- 9.180); 'blood transfusion' (OR = 2.305, 95%CI:1.578-3.369) and
      'invasive physical examination' (OR = 1.258, 95% CI:1.021-1.549) appeared to be
      important. Age seemed a risk factor for HCV infection. "Sharing razor" was a
      specifically important risk factor among the 30- year-olds. "Having received
      acupuncture" was noticed a risk factor only among people at 50-59 years of age
      while "Having received invasive physical examination" was important in the 50-59
      and 60-69 year-olds. CONCLUSION: High anti-HCV positive rate was observed in
      people at middle of aged population, as well as in those with poor education or
      under 'floating'. Unsafe blood donation or having received blood-product
      transfusion might be the risk factors in the last decades. Factors as sharing
      razor, having received acupuncture or invasive examination might be specifically
      risky in different populations.

PMID- 25598251
TI  - [Sildenafil use and relevant risk factors among middle-aged or elderly male
      clients of female commercial sex workers in the central areas of Guangxi, China].
AB  - OBJECTIVE: To understand the illegal sidenafil use among middle-aged and elderly
      male clients of female sex workers (FSWs) in central region of Guangxi as well as
      on related risk factors. Initial evaluation regarding the effect of illegal
      sidenafil use on HIV infection among the middle-aged and elderly men was also
      conducted. METHODS: A survey was conducted among the over 50-year-olds male
      clients of low-grade prostitutions in central areas of Guangxi. Information on
      demographics, related behavior, and illegal sidenafil use was collected. 5 ml
      blood sample were taken to test antibodies of HIV and syphilis. PASW Statistics
      18.0 was used for data analysis. RESULTS: 2 056 questionnaires were completed.
      23.1% of the participants said they had ever used illegal sidenafil. The risk of
      sildenafil use was low among the male clients who were not over 60 years old (OR
      = 0.586, 95% CI:0.459-0.749). The risks of sildenafil use among the male clients
      with frequencies(in the past 30 days) of having commercial sex behavior were:only
      once (OR = 0.184, 95%CI:0.090- 0.378), twice (OR = 0.187, 95%CI:0.089-0.378) or
      three times (OR = 0.181, 95%CI: 0.085-0.384) lower than those with more than five
      times. Being single (OR = 0.608, 95% CI: 0.396-0.933), married/cohabiting (OR =
      0.533, 95% CI:0.391-0.727), having unstable partners (OR = 0.558, 95%CI:0.393
      0.792) seemed to be protective on those who used sildenafil, among the study
      population. Factors as 'never use the condom (OR = 1.642, 95%CI:1.125-2.397) or
      'seldom use as condom (OR = 1.840, 95%CI:1.278-2.648) when having commercial sex,
      were under high risk among the sildenafil users. Forty-seven subjects were HIV
      positive, with the prevalence as 2.29% in this study population. Male clients of
      the FSWs who used sidenafil were under 60 years of age and with higher risk of
      HIV infection. CONCLUSION: people who were >=60 years old, divorced/widowed/
      separated, with frequencies (in the past 30 days) of having commercial sex more
      than 5 times, never or occasionally using a condom when having commercial sex
      etc., appeared at high risk. Middle-aged and elderly male clients who used
      sildenafil or sildenafil-like drugs were under high risk of contracting HIV
      infection.

PMID- 25598252
TI  - [Club drug use and its association with syphilis infection among female sex
      workers].
AB  - OBJECTIVE: To understand the prevalence rates of club drug use and how it
      associated with syphilis infection among female sex workers (FSWs) in different
      areas of China so as to provide reference for developing intervention programs.
      METHODS: In each of the study site, different kinds of venues where FSWs
      solicited clients were mapped and grouped into three strata. The number of FSWs
      at each venue was enumerated. A stratified proportional sampling design was
      adopted to recruit FSWs. Questionnaire survey was conducted to gather data on
      demographic information, club drug use and sexual behaviors. Blood samples were
      taken and tested for syphilis. Factors associated with syphilis infection and
      club drug use were assessed using univariate and multivariate logistic regression
      models. RESULTS: Results of the 1 630 participants, 120 (7.4%)used club drugs in
      the past 12 months, and 5.4% (88/1 630)tested positive for syphilis. Syphilis
      positive rate was not significantly different between FSWs who used club drugs
      and those who did not. Data from multivariate logistic regression analysis
      indicated that club drug use was associated with following factors as sites of
      the study, hometown of the FSWs, marital status, education level, having had STD
      symptoms or history of injecting drugs in the past 12 months of the sex workers.
      CONCLUSION: Club drug use was highly prevalent among FSWs. Further studies are
      warranted to fully explore the association between club drug use and the risk of
      HIV/STD transmission.

PMID- 25598253
TI  - [Prevalence of human immunodeficiency virus and associated risk factors among men
      who have sex with men in the major regions of Pearl River Delta, from 2009 to
      2013].
AB  - OBJECTIVE: To examine the HIV prevalence and associated risk factors among men
      who have sex with men (MSM) in the Pearl River Delta (PRD) region, in order to
      provide scientific basis for assessment on HIV prevention programs. METHODS:
      Surveillance projects on HIV infection status and risk factors were carried out
      among MSM in six prefectural PRD cities, based on the national sentinel
      surveillance program among MSM. RESULTS: A total of 8 770 MSM were recruited in
      the six PRD prefectural cities from 2009 to 2013. The overall prevalence rates of
      HIV among MSM during 2009 and 2013 were 4.7% , 9.7% , 10.6% , 12.9% and 11.4% ,
      respectively, appeared an increasing trend. HIV related high-risk behaviors were
      commonly seen among MSM. The proportion of consistent condom use during anal sex
      in the last six months was 46.3%. Associated risk factors for HIV infection among
      MSM would include older age, being non-permenant residents, inconsistent condom
      use, history of having had sexually transmitted diseases and without having
      received intervention services in the last year. CONCLUSION: High-risk behaviors
      were popular in the MSM population that causing the HIV transmission to expand
      among the MSM population in the major region of PRD. It seemed necessary to
      reinforce the publicity and education programs as well as effective behavior
      intervening measures among the MSM group.

PMID- 25598254
TI  - [Current status regarding the levels of risks on cardiovascular diseases among
      the hypertensives in Zhejiang].
AB  - OBJECTIVE: To assess the cardiovascular disease-related risk levels among
      hypertensive people in Zhejiang. METHODS: Subjects were selected from local
      residents aged >=18 years old, using the multi stage stratified-random sampling
      method. All participants accepted physical examinations including blood tests for
      lipids, fasting blood glucose, 2 hours blood glucose and physical measurements
      for obesity and blood pressure in the year 2010. RESULTS: Totally, 17 437
      subjects were finally included in the study, in which 5 227 were diagnosed as
      having hypertension, with 'grade one hypertension' the majority. Cardiovascular
      disease-related risk factors would include older age (male >55 years, female >65
      years), smoking, abnormal fasting glucose, impaired glucose tolerance, abnormal
      TC, abnormal HDL-C, abdominal obesity and obesity, with rates as 42.78% , 20.89%,
      5.31%, 8.35%, 9.87%, 35.66%, 40.55% and 13.93%. Most of the hypertensive people
      had two (30.44%) or three risk factors (29.96%). Proportions of low, medium, high
      or very high risks were 9.70% , 47.71% , 18.81% and 23.78% , respectively in
      those people with hypertension. Significant differences on cardiovascular risk
      stratification were found between age groups, sex and regions. There were also
      statistically significant differences noticed, regarding the levels of
      cardiovascular disease related risks between in patients aware or unaware of the
      diseases, under control or uncontrolled of the situation. CONCLUSION: People
      under high risk or very high risk on cardiovascular disease did exist in
      Zhejiang, especially in those 60-year-olds, males and urban residents.

PMID- 25598255
TI  - [Association between sedentary life style and risks of metabolic syndrome and
      diabetes mellitus type 2].
AB  - OBJECTIVE: To explore the association of sedentary life style with risk of
      metabolic syndrome (MS) and diabetes mellitus type 2(T2DM). METHODS: A total of 6
      016 local residents aged 18 years or older in Fujian province were recruited by
      multi-stage stratified cluster sampling method in 2010-2011. Data, including
      demographic information, physical activity and sedentary time were collected.
      Indices related to height, weight, waist circumference, blood pressure and blood
      lipid were determined while MS and T2DM were diagnosed by IDF (2005) and WHO
      (1999) criteria. Logistic regression was used to estimate the correlations
      between sedentary behavior and MS or T2DM. RESULTS: The prevalence rates of MS
      and T2DM were 19.0% and 8.0% respectively, in local residents aged 18 years or
      older, in Fujian province. The overall rate of sedentary behavior was 18.1%, with
      the mean sedentary time as 4.3 hours. Both data showed significantly differences
      (P < 0.001) among control group,MS without T2DM group,MS with T2DM group and T2DM
      without MS group. Compared with the group of sedentary time <2.0 h/d, 1) the
      group with 2.0-3.5 h/d was significantly correlated with MT group (OR = 1.44, 95%
      CI:1.03-2.03, P < 0.05), 2) groups of 3.5-6.0 h/d and >=6.0 h/d were
      significantly correlated with M, T, MT group, respectively (OR:1.49-1.76 and 1.28
      1.58 respectively, 95% CI:1.19-2.45 and 1.02-2.23 respectively, P < 0.05), and 3)
      sedentary behavior was independently associated with an increased risk of MT
      group (OR = 1.82, 95% CI: 1.33-2.48, P < 0.01) and M group (OR = 1.43, 95%CI:1.14
      1.78, P < 0.01), after the adjustment for factors as age, sex, cigarette smoking,
      alcohol drinking,BMI, education, occupation, sedentary behavior/sedentary time.
      CONCLUSION: MS and T2DM were associated with sedentary lifestyle, but these
      findings should be confirmed through further longitudinal studies.

PMID- 25598256
TI  - [Outcomes and correlated factors in patients with impaired fasting glucose: a ten
      year follow-up analysis].
AB  - OBJECTIVE: To investigate the outcomes and relative risk factors in subjects with
      impaired fasting glucose in Inner Mongolia, China. METHOD: A total number of 32
      villages in Kezuohou Banner and Naiman areas in Inner Mongolia were selected as
      the baseline surveys study fields from 2002 to 2003. Patients with IFG (5.6
      mmol/L<=FPG<7.0 mmol/L) but without history of diabetes were selected as the
      study subjects. A follow-up study was conducted in 2013. Multinomial logistic
      regression analysis was used to evaluate the correlated factors. RESULTS: There
      were 384 patients with IFG recruited in the study. Out of them, 150 (39.1%)
      progressed to normoglycaemia, 174 (45.3%) remained as IFG, and 60 (15.6%)
      developed into type 2 diabetes mellitus. Through adjustment multivariately,
      patients that returning to the status of normoglycaemia were significantly
      associated under the function of TG (OR = 0.692, 95%CI:0.502-0.952, P < 0.05)and
      those developed to diabetes were significantly associated with factors as age(OR
      = 1.052, 95%CI:1.014-1.090, P < 0.05) or obesity (OR = 2.924, 95% CI:1.353-6.320,
      P < 0.05). CONCLUSION: 15.6% of the IFG patients developed diabetes mellitus
      among the Inner Mongolian population. Elevated TG was an inhibition factor for
      patients returning to normoglycaemia while both age and abdominal obesity were
      risk factors for the development of diabetes in the Inner Mongolian population.

PMID- 25598257
TI  - [Impact analysis on the health management programs among community-based 0-36
      month-olds on their growth and development].
AB  - OBJECTIVE: To analyze the impact of implementation on health management programs
      among the community-based 0-36-month-olds regarding their growth and development.
      METHODS: 18 Monitoring Bodies in 8 pilot areas were selected to enroll this
      study, using a multistage stratified cluster sampling method. All the children
      aged 0 to 36 months were followed, according to the health management
      specification, and their health archives were collected. RESULTS: A total of 13
      464 children were involved in the specified management program with a total of 59
      648 person-time under follow-up, with 54.26% of them were boys. Results from the
      multi-layer linear model indicated that the average height of children in the
      specified management group was higher than that in the non-standardized
      management group. Children in the specification management group, their weight
      gain had also been more effectively controlled. At the same time, with the
      increasing number of follow-ups according to the specification, the prevalence
      rates of under weight, stunt, emaciation and overweight were all significantly
      decreased (P < 0.05). CONCLUSION: The implementation of the community-based
      programs on 0-36-month-olds regarding their health management specification had
      improved children's growth and development.

PMID- 25598258
TI  - [A cross sectional survey on the prevalence of food intolerance and its
      determinants through physical checkup programs in the elderly].
AB  - OBJECTIVE: To explore the prevalence of food intolerance and its determinants in
      healthcare elderly in China. METHODS: A cross sectional survey was carried out
      from August 1(st), 2008 to June 30(th), 2009, that including 736 60-year-olds
      from a Health Management Research Institute, Chinese PLA General Hospital. Data
      was double entried in computer and organized by EpiData 3.0. Non conditional
      logistic regression model was used for odd ratio (OR) and 95% CI, with the use of
      SPSS 13.0. RESULTS: The three leading foodstuff on intolerance were crab, egg and
      shrimp, with the prevalence rates as 35.9% , 28.8% and 15.1% respectively.
      Results from the multiple regression analysis showed that the crab intolerance
      was associated with Helicobacter pylori infections (P < 0.05). The OR(95%CI) of
      Helicobacter pylori infections (DOB>=4) was 1.544 (1.139-2.091). CONCLUSION: The
      three leading intolerance foods were egg, crab and shrimp. Crab intolerance was
      associated with Helicobacter pylori infections. To reduce the risk of crab
      intolerance, it was necessary to control the infection caused by Helicobacter
      pylori.

PMID- 25598259
TI  - [Change on the rate of children's finger metaphysics in the non-Kaschin-Beck
      disease areas of China].
AB  - OBJECTIVE: 36 non-Kaschin-Beck disease villages in five provinces including
      Jilin, Liaoning, Shaanxi, Shanxi and Inner Mongolia in the severe endemic areas
      of Kaschin-Beck disease (KBD) were selected. The aim of this project was to
      provide the basis showing these KBD villages had already eliminated the KBD.
      METHODS: Fully digital versatile X-ray radiography systems(DR) was used to shoot
      children's right hand X-ray, in accordance with the "Kashin-Beck Disease
      Diagnosis Standard" (WS/T 207-2010) for diagnosis. RESULTS: Results indicated
      that children showing metaphyseal changes only appeared in 13 of the 36 villages,
      where the rate of change on metaphyseal was less than or equal to three percent.
      CONCLUSION: When KBD had been eliminated in a village, the rate of change on aged
      7 to 12 children's metaphyseal would have been less than three percent.

PMID- 25598260
TI  - [Estimation on the indirect economic burden of disease-related premature deaths
      in China, 2012].
AB  - OBJECTIVE: To estimate the indirect economic burden of disease-related premature
      deaths in China, 2012. METHODS: Both human capital approach and friction cost
      methods were used to compute the indirect economic burden of premature deaths
      from the following sources: mortality from the national disease surveillance
      system in 2012, average annual income per capita from the China Statistic
      Yearbook in 2012, population size from the 2010 China census, and life expectancy
      in China from the World Health Organization life table. RESULTS: Data from the
      Human Capital Approach Estimates showed that the indirect economic burden of
      premature deaths in China was 425.1 billion in 2012, accounting for 80/00 of the
      GDP. The indirect economic burden of chronic non-communicable diseases associated
      premature deaths was accounted for the highest proportion(67.1%, 295.4 billion),
      followed by those of injuries related premature deaths (25.6% , 108.9 billion),
      infectious diseases, maternal and infants diseases, and malnutrition related
      deaths (6.4% , 26.9 billion). The top five premature deaths that cause the
      indirect economic burden were malignancy, cardiovascular diseases, unintentional
      injuries, intentional injuries, and diseases of the respiratory system. The
      indirect economic burden of premature deaths mainly occurred in the population of
      20-59 year-olds. Under the Friction Cost method, the estimates appeared to be
      0.11%-3.49% of the total human capital approach estimates. CONCLUSION: Premature
      death caused heavy indirect economic burden in China. Chronic non-communicable
      diseases and injuries seemed to incur the major disease burden. The indirect
      economic burden of premature deaths mainly occurred in the working age group.

PMID- 25598261
TI  - [Direct economic burden of cerebrovascular disease, during 1993-2008 in China].
AB  - OBJECTIVE: To evaluate the status and trend of direct economic burden on
      cerebrovascular disease, from 1993 to 2008 in China. METHODS: Using two-step
      model to calculate the economic cost with related trend of cerebrovascular
      disease within the population among the over 30-year-olds, from 1993 to 2008.
      Data was gathered from the National Health Service Surveys Analysis Reports of
      1993, 1998, 2003 and 2008, that including both direct outpatient and inpatient
      cost. RESULTS: There appeared a significant increase on the burden of
      cerebrovascular diseases in the period of 15 years, with direct economic cost
      increasing from 8.473 billion to 103.125 billion RMB. In fact, the actual
      increase was 5.3 times, without the influence of the price. The average annual
      growth rate was 13.1%, exceeding the rate of total expenditure on health and GDP
      during the same time span. In addition, the growth rate in 2003-2008 was the
      fastest, which appeared to be 19.8%. CONCLUSION: Burden that caused by
      cerebrovascular disease on individuals and the whole society was heavy which
      warrented further theoratical and practical studies on it.

PMID- 25598263
TI  - [Spatial aggregation of 438 human infections with avian influenza A (H7N9) in the
      mainland of China].
AB  - OBJECTIVE: To investigate the spatial distribution and growing trend of 438 human
      infection with the H7N9 avian influenza virus in mainland China, and to provide
      evidence for developing scientific prevention and control strategies. METHODS:
      438 human infection with the avian influenza A (H7N9) cases from February 2013 to
      May 2014 in mainland China were studied and data collected to establish a
      database for the development of geographic information system. Trend surface
      analysis and spatial autocorrelation analysis were used to study the spatial
      distribution. Descriptive epidemiological method was utilized to analyze the
      demographic characteristic. RESULTS: From June 2013 to May 2014, cases had an
      overall national increase, but significantly decreasing in Shanghai. A trend
      surface was established for human infection with avian influenza A (H7N9) in the
      mainland of China, showing that the incidence was increasing obviously from north
      to south and the line slope declined from west to east. Distribution pattern of
      the cases varied within different time series and regional levels. The overall
      Moran's I coefficient of the provincial level from February to May in 2013 and
      the coefficient of the city level from June 2013 to May 2014 were 0.144 718 and
      0.117 468, respectively, with the differences statistically significant (P <
      0.05). According to the analysis of the local autocorrelation and hot spot,
      northern Zhejiang and southern Guangdong showed high spatial clusters of human
      infection with avian influenza A (H7N9) (Z>2.58). CONCLUSION: From February 2013
      to May 2014, the spatial correlation at the provincial level decreased. However,
      the spatial correlation and the numbers of hot spots at the city level were both
      increasing. Effective measures should be taken accordingly, follwoing the
      distributive characteristics.

PMID- 25598262
TI  - [Study on the cause-specific mortality attributable to smoking among males in
      Tianjin].
AB  - OBJECTIVE: Prevalence rates related to smoking and second hand smoking exposure
      were high in Tianjin, particularly among males. Our study aimed to analyze all
      cause of deaths attributable to smoking in male citizens in Tianjin. METHODS:
      Data on 38 312 death cases aged 18-69 years old were collected from 2010 to 2012.
      Odds ratio of deaths on different disease and excess deaths attributed to
      smoking, after adjusting age and education level were calculated. RESULTS: 22.57%
      of the male death cases were caused by smoking in Tianjin, and smokers'5 years of
      life loss due to the habit of smoking. Compared to the non-smokers, the mortality
      risks appeared as:lung cancer (OR = 3.10, 95% CI:2.80-3.44), heart disease (OR =
      1.47, 95% CI:1.36-1.59), and stroke (OR = 1.41, 95% CI:1.30-1.53). The mortality
      risk attributed to smoking was higher in urban than that in rural areas. Factors
      as smoking initiated at early age and plenty daily cigarette consumption were
      both associated with risk of high mortality. CONCLUSION: Results from our study
      addressed the problem that smoking had been a major risk factor for mortality and
      productivity loss in male adults in Tianjin. Prevention programs and initiatives
      on reducing the rates of smoking and second hand smoking should be strengthened
      to decrease the smoking-related deaths in Tianjin.

PMID- 25598264
TI  - [Epidemiological investigation on respiratory diseases in 1 300 children, in
      Jinan, Shandong].
AB  - OBJECTIVE: To analyze the characteristics of respiratory diseases and to provide
      scientific basis for developing relevant control measures. METHODS: 1 300
      children with respiratory diseases were treated in hospitals, from Jan. 2013 to
      May 2014, in the city of Jinan. Characteristics of respiratory diseases were
      analyzed. RESULTS: The distribution of respiratory diseases in children appeared
      as: 373 cases of pneumonia (28.7%), 3 cases of pulmonary tuberculosis (0.2%), 467
      cases of acute bronchitis (35.9%), 102 cases of asthma (7.8%), and 355 cases of
      upper respiratory tract infection (27.3%). The upper respiratory tract infection
      contained 168 cases of tonsillitis (12.9%), 91 cases of pharyngitis (7.0%), 52
      cases of laryngitis(4.0%)and 44 cases of iaryngopharyngitis (3.4%). The age
      distribution of cases with children respiratory diseases appeared as:71 cases <1
      years old (5.5%), 385 cases as 1-2 years old (29.6%), 534 cases as 3-6 years old
      (41.1%), 258 cases as 7-12 years old (19.8%)and 52 cases as >13 years old (4.0%).
      The seasonal distribution of children respiratory diseases appeared as:364 cases
      in Spring (28.0% ), 163 cases in summer (12.5%), 315 cases in autumn (24.2%)and
      458 cases in winter (35.2%). Regional distribution of children respiratory
      diseases appeared as:516 cases in urban area (39.7%), 225 cases in suburb
      (17.3%), 376 cases in townships (28.9%)and 183 in villages (14.1%). 725 strains
      were isolated and identified that containing 349 strains(48.1%) of Mycoplasma
      pneumoniae, 136 strains (18.8%) of Haemophilus influenza, 103 strains (14.2% ) of
      Streptococcus pneumoniae, 82 strains (11.3% ) of Klebsiella pneumoniae, 38
      strains (5.2%) of Acinetobacter baumannii, 35 strains(4.8%) of Enterobacter
      cloacae, 22 strains (3.0%) of Streptococcus pyogenes, 17 strains (2.3%) of
      Alcaligenes, 16 strains (2.2% of Candida albicans)and 9 strains (1.2%) of
      Flavobacterium indologenes. 1 288 cases (99.1%) were cured. CONCLUSION: The
      common respiratory diseases would include bronchiolitis, pneumonia and upper
      respiratory tract infections in children, mostly attacking 3-6 year-olds at
      preschool stage, with spring, winter, urban and township as the prevalent seasons
      and areas.

PMID- 25598265
TI  - [Multivariate analysis on the association between acquired multi-drug resistant
      organism infection and ventilator-associated pneumonia:evidence from a nested
      case-control study of eight ICUs].
AB  - OBJECTIVE: The aim of this study was to explore the association between acquired
      multi-drug resistant organism (MDRO) and ventilator-associated pneumonia (VAP) in
      patients hospitalized at the intensive care unit(ICU). METHODS: Real-time
      monitoring system for hospital infection was used to track VAP patients. The
      period of study was from January 1, 2013 to December 31, 2013. Both a nested case
      control study design and logistic multivariable regression model were performed
      to explore the association. RESULTS: A total of 142 VAP cases and 342 non-VAP
      controls were available in this study. Duration of Hospital stay, ICU stay and
      mechanical days were statistically significant between the case and the control
      group (P<=0.001). Compared with MDRO negative patient, the MDRO colonization or
      infection patients showed an 3.05-time increase on the risk of VAP (adjusted OR =
      4.05, 95% CI:2.51-5.46). Remarkably,MDRO-positive patients were significantly
      associated with increased duration of mechanical ventilation and antimicrobial
      drug use (P < 0.001). CONCLUSION: MDRO colonized and infection patients would
      significantly increase the risks of VAP, with prolonged hospitalization and ICU
      stay. Effective measures should be taken to promote and control patient's safety
      at the hospital.

PMID- 25598266
TI  - [Study on the relationship between prenatal monitoring index in intrahepatic
      cholestasis of pregnancy and perinatal prognosis].
AB  - OBJECTIVE: To investigate the association between prenatal monitoring index in
      intrahepatic cholestasis of pregnancy and the perinatal prognosis, as well as the
      characteristics of perinatal situations. METHODS: A retrospective study on the
      clinical data of 88 cases intrahepatic cholestasis of pregnancy and prognosis
      that were treated in our hospital from Jan. 2011 to Jan. 2014 was carried out.
      Relationship between prenatal monitoring index in intrahepatic cholestasis of
      pregnancy and perinatal prognosis, together with the epidemiological features of
      infants were analyzed. RESULTS: The incidence rates of perinatal meconium stained
      amniotic fluid, asphyxia neonatorum, premature and fetal distress were
      significantly higher in the study group than those in the controls, with
      differences statistically significant (P < 0.05). The levels of CG,ALT,AST, TBIL,
      DBIL and TBA in puerperant with bad perinatal situation were significantly higher
      than puerperant with good perinatal situation, with the difference statistically
      significant(P < 0.05). Results from the multiple regression analysis indicated
      that close relations did exist between CG,ALT,AST, TBIL, TBA and adverse
      perinatal prognosis. The main perinatal risks were related to meconium stained
      amniotic fluid (33.3%), prematurity (28.6%), fetal distress (20.6%), asphyxia
      neonatorum (15.9%) and stillbirth (1.6%). CONCLUSION: The rate of adverse
      perinatal prognosis was low in intrahepatic cholestasis of pregnancy, with most
      frequently seen as meconium stained amniotic fluid. It was necessary to monitor
      the level of prenatal CG, ALT, AST, TBIL and TBA in puerperant in predicting the
      perinatal prognosis.

PMID- 25598267
TI  - [Analysis on the research fronts of A H1N1 influenza by bibliometrics and
      information visualization].

PMID- 25598268
TI  - [Plasmid types, functions of Yersinia pestis and their epidemiological
      significance].

PMID- 25598269
TI  - Predicting bioaccumulation of polycyclic aromatic hydrocarbons in soft-shelled
      clams (Mya arenaria) using field deployments of polyethylene passive samplers.
AB  - Biota-sediment accumulation factors (BSAF), frequently used to predict tissue
      concentrations of organisms living within and above sediments contaminated with
      hydrophobic organic chemicals, often produce inaccurate estimates. Hence, freely
      dissolved porewater concentrations, CW , have also been investigated as
      predictors of organism tissue concentrations, but they are more difficult to
      measure than bulk sediment concentrations (used with BSAF). In situ passive
      sampling methods, however, make it possible to deduce CW with less effort than
      required to measure the value directly and make it possible to relate CW with
      tissue concentrations of undisturbed, native organisms. In the present study,
      polyethylene passive samplers containing performance reference compounds (d10
      phenanthrene, d10-pyrene, and d12-chrysene) were deployed in diverse sediment
      beds near Boston, Massachusetts, USA, for a 1-wk period. Clams (Mya arenaria) and
      sediments were then collected from the deployed sediment beds. Concentrations of
      3 polycyclic aromatic hydrocarbons (PAHs; phenanthrene, pyrene, and chrysene)
      were measured in the porewaters, in clam tissues, and in the bulk sediment. Biota
      sediment accumulation factors and polyethylene-deduced CW were used to predict
      organism tissue concentrations. Ratios of predicted-to-measured values showed
      that the BSAF method over-predicted tissue concentrations in M. arenaria by up to
      2 orders of magnitude. The polyethylene-deduced CW method resulted in average
      ratios closer to 1 (0.43 +/- 0.26, 3.7 +/- 2.5, and 1.1 +/- 1.2 for phenanthrene,
      pyrene, and chrysene, respectively, N = 26, uncertainty = +/- 1sigma).

PMID- 25598270
TI  - Effects of dietary folate intake on migraine disability and frequency.
AB  - BACKGROUND: Migraine is a highly disabling disease affecting a significant
      proportion of the Australian population. The methylenetetrahydrofolate reductase
      (MTHFR) C677T variant has been associated with increased levels of homocysteine
      and risk of migraine with aura (MA). Folic acid (FA), vitamin B6 , and B12
      supplementation has been previously shown to reduce increased levels of
      homocysteine and decrease migraine symptoms. However, the influence of dietary
      folate intake on migraine has been unclear. The aim of the current study was to
      analyze the association of dietary folate intake in the form of dietary folate
      equivalent, FA, and total food folate (TFF) on migraine frequency, severity, and
      disability. METHODS: A cohort of 141 adult females of Caucasian descent with MA
      was genotyped for the MTHFR C677T variant using restriction enzyme digestion.
      Dietary folate information was collected from all participants and analyzed using
      the "FoodWorks" 2009 package. Folate consumption was compared with migraine
      frequency, severity, and disability using linear regression. RESULTS: A
      significant inverse relation was observed between dietary folate equivalent (R(2)
      = 0.201, B = -0.002, P = .045, 95% confidence interval [CI] [-0.004, -0.001])
      and FA (R(2)  = 0.255, B = -0.005, P = .036, 95% CI [-0.009, -0.002]) consumption
      and migraine frequency. It was also observed that in individuals with the CC
      genotype for the MTHFR C677T variant, migraine frequency was significantly linked
      to FA consumption (R(2)  = 0.106, B = -0.004, P = .029, 95% CI [-0.007, -0.004]).
      CONCLUSIONS: The results from this study indicate that folate intake in the form
      of FA may influence migraine frequency in female MA sufferers.

PMID- 25598271
TI  - Influence of zeolite pore structure on product selectivities for protolysis and
      hydride transfer reactions in the cracking of n-pentane.
AB  - The conversion of n-pentane was carried out to examine the effects of reaction
      conditions on changes in product selectivities at 823 K, using zeolites with 10-
      and 12-membered rings. We also investigated the influence of the pore structure
      of these zeolites on their catalytic activities for both protolysis and hydride
      transfer reactions. In the first half of this work, we examined the influence of
      acidic proton concentration and n-pentane pressure on the reaction rates for
      protolysis and hydride transfer reactions using ZSM-5 zeolites. The rates of
      hydride transfer reactions were more influenced by pentane pressure compared to
      protolysis reactions, and were proportional to the square of n-pentane pressure
      and the concentration of acidic protons. In the second half of this work, the
      influence of the zeolite pore structure on changes in product selectivities with
      n-pentane conversion and that on the rates of protolysis and the hydride transfer
      reactions were revealed using various zeolites with 10- and 12-membered rings.
      The catalytic activities of zeolites for the protolysis and hydride transfer
      reactions were influenced more by the spatial volume of the zeolite cavity than
      the acid strength of protons on the zeolite. 

PMID- 25598272
TI  - Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder
      testicular dysgenesis is associated with a higher risk of malignancy.
AB  - All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an
      in situ stage (CIS) of protracted evolution. The adult CIS is well characterized,
      but there is debate on the phenotype of infantile CIS, its distinction from
      delayed maturation of germ cells and prognostic potential. A large series of 43
      patients with Disorders of Sex Development (DSD) and dysgenetic testes (90%
      ranging from neonates to 12 years, mean age 4.7 years), was studied by
      quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA),
      expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy
      and evolution to CIS and invasive TGCT. Findings were compared with those of
      normal testes. The type of gonads present defined three groups of patients:
      bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for
      combined, n = 13), and ovarian-testicular combinations (OT-DSD, n = 9). There
      were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two
      patients with adult CIS, bilateral in one (total of 3 adult CIS). Two patients
      had bilateral seminomas one at 12-17 and the other at 23 years. Histological
      dysgenesis was significantly higher in CT-DSD (p < 0.05), that had only 1 CIS.
      The highest frequency of GCA was in BT-DSD (p < 0.05), which coincided with a
      total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher
      (63%) than diploidy (p < 0.02), and GCA were more frequent in aneuploid than in
      diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive. Finally,
      there was a significant association between the triad Aneuploidy + GCA + OCT 3/4
      positivity and the incidence of CIS (Fisher Exact test p < 0.002, relative risk
      7.0). The degree of testicular dysgenesis (derived from abnormal organization of
      Sertoli cells in fetal testicular cords) is inversely related to the incidence of
      CIS. Our data demonstrate that the combined use of OCT 3/4 expression,
      quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes
      can satisfactorily identify infantile CIS with high risk of malignant evolution
      and set it aside from delayed germ cell maturation with lower or nil neoplastic
      potential. 

PMID- 25598273
TI  - Fluorinated aromatic polyimides as high-performance electret materials.
AB  - In view of the increasing significance of technology-driven devices such as
      microelectromechanical systems, energy-harvesting devices, and organic field
      effect transistors, polymer electret materials with durable electret performance
      at elevated temperatures become more and more important. However, typical polymer
      electret materials lose their performance at elevated temperatures. To provide
      polymer materials with improved electret performance over a broad temperature
      range, a series of aromatic polyimides with different degree of
      fluorosubstitution is presented. Isothermal surface potential decay measurements
      at elevated temperatures reveal that minor differences in the chemical structure
      have a major influence on the electret behavior. The best performance is found
      for the polyimide containing a hexafluoroisopropylidene moiety in both the
      bisanhydride- and the diamine-based unit. Excellent long-term charge storage
      stability at 120  degrees C is observed. From the initial surface charge 94%
      remains after 24 h. This polyimide even tolerates short-term exposure of 30 s at
      300  degrees C with almost no loss of performance. These findings demonstrate
      that this particular polyimide is suitable for device applications at elevated
      temperatures during fabrication and use. 

PMID- 25598274
TI  - Painless, safe, and efficacious noninvasive skin tightening, body contouring, and
      cellulite reduction using multisource 3DEEP radiofrequency.
AB  - In the last decade, Radiofrequency (RF) energy has proven to be safe and highly
      efficacious for face and neck skin tightening, body contouring, and cellulite
      reduction. In contrast to first-generation Monopolar/Bipolar and "X -Polar" RF
      systems which use one RF generator connected to one or more skin electrodes,
      multisource radiofrequency devices use six independent RF generators allowing
      efficient dermal heating to 52-55 degrees C, with no pain or risk of other side
      effects. In this review, the basic science and clinical results of body
      contouring and cellulite treatment using multisource radiofrequency system
      (Endymed PRO, Endymed, Cesarea, Israel) will be discussed and analyzed.

PMID- 25598275
TI  - Tuberculosis and diabetes mellitus in the Republic of Kiribati: a case-control
      study.
AB  - OBJECTIVES: To better inform local management of TB-diabetes collaborative
      activities, we aimed to determine the prevalence of diabetes among persons with
      and without TB and to determine the association between TB and diabetes in
      Kiribati, a Pacific Island nation. METHODS: We compared consecutively enrolled TB
      cases to a group of randomly selected community controls without evidence of TB.
      Diabetes was diagnosed by HbA1c, and clinical and demographic data were
      collected. A tuberculin skin test was administered to controls. The chi-square
      test was used to assess significance in differences between cases and controls.
      We also calculated an odds ratio, with 95% confidence intervals, for the odds of
      diabetes among cases relative to controls. Unweighted multivariate logistic
      regression was performed to adjust for the effects of age and sex. RESULTS: A
      total of 275 TB cases and 499 controls were enrolled. The diabetes prevalence in
      cases (101, 37%) was significantly greater than in controls (94, 19%) (adjusted
      odds ratio: 2.8; 95% CI 2.0-4.1). Fifty-five percent (108) of all diabetic
      diagnoses were new; this proportion was higher among controls (64.8%) than cases
      (46.5%). Five patients with TB were screened to detect one patient with diabetes.
      CONCLUSIONS: There is a strong association between TB and diabetes in Kiribati
      and bidirectional screening should be conducted in this setting.

PMID- 25598276
TI  - Viral PCR positivity in stool before allogeneic hematopoietic cell
      transplantation is strongly associated with acute intestinal graft-versus-host
      disease.
AB  - Acute graft-versus-host disease (aGVHD) can be triggered by inflammatory
      conditions, including infections and mucositis. We investigated the association
      between PCR positivity for gastrointestinal (GI) viruses in stool before
      hematopoietic cell transplantation (HCT) and intestinal aGVHD using Cox
      proportional hazard models. We included 48 consecutive HCT patients (28 with
      malignancies and 20 with nonmalignancies) without GI symptoms before HCT. Fifteen
      patients were GI virus positive: 9 adenovirus, 3 norovirus, 2 parechovirus, and 1
      astrovirus. Overall survival was 58% +/- 8%. The cumulative incidence of aGVHD
      grade 2 to 4 was 43% +/- 8% (n = 18) after a median of 47 days (range, 14 to
      140). In univariate analysis, GI virus PCR positivity was the only predictor for
      aGVHD (P = .008): within the group of GI virus PCR-positive patients, the
      cumulative incidence of aGVHD 2 to 4 was 70% +/- 12% versus 29 +/- 8% in the PCR
      negative group (P = .004). In conclusion, GI virus PCR positivity before HCT
      predicted development of intestinal aGVHD. These results may ultimately affect
      monitoring, aGVHD prophylaxis, and treatment, as well as rescheduling of elective
      HCTs.

PMID- 25598278
TI  - Commentary on the significance of pain catastrophizing in clinical manifestations
      of patients with lumbar spinal stenosis: mediation analysis with bootstrapping.
AB  - COMMENTARY ON: Kim HJ, Cho CH, Kang KT, Chang BS, Lee CK, Yeom JS. The
      significance of pain catastrophizing in clinical manifestations of patients with
      lumbar spinal stenosis: mediation analysis with bootstrapping. Spine J
      2015;15:238-46 (in this issue).

PMID- 25598277
TI  - Comparison of conditioning regimens with or without antithymocyte globulin for
      unrelated cord blood transplantation in children with high-risk or advanced
      hematological malignancies.
AB  - The role and potential efficacy of antithymocyte globulin (ATG) in patients
      receiving cord blood transplantation (CBT) remain controversial. We
      retrospectively evaluated the effect of ATG on patient outcomes in 207 children
      with high-risk or advanced hematological malignancies at 8 child blood disease
      centers in China. The cumulative incidence of platelet recovery on day 100 was
      significantly lower in the ATG cohort compared with the non-ATG cohort (77.3%
      versus 89.8%) (P = .046). There was no significant difference in the incidence of
      grade II to IV acute and chronic graft-versus-host disease (GVHD), and
      transplantation-related mortality (TRM) between the 2 groups (P = .76, P = .57,
      and P = .46, respectively). The incidence of CMV infection was significantly
      higher among the ATG group compared with that among the non-ATG group (P = .003).
      The 5-year cumulative incidence of relapse was significantly higher in the ATG
      cohort (30.7% versus 15.4%) (P = .009). Overall survival in the non-ATG group was
      slightly higher than that of the ATG cohort (64.1% versus 52.1%, P = .093) and
      leukemia-free survival in the non-ATG cohort was significantly higher than in the
      ATG cohort (56.6% versus 37.7%, P = .015). Our study demonstrated that, for high
      risk or advanced childhood hematological malignancies receiving unrelated CBT,
      patients who received conditioning that omitted ATG had a faster platelet
      recovery, a comparable GVHD and TRM, a significantly lower relapse risk, and an
      improved long-term survival compared with those patients who received ATG in the
      conditioning.

PMID- 25598279
TI  - Fusion surgery for lumbar degenerative disc disease: still more questions than
      answers.
AB  - COMMENTARY ON: Yoshihara H, Yoneoka D. National trends in the surgical treatment
      for lumbar degenerative disc disease: United States, 2000 to 2009. Spine J
      2015;15:265-71 (in this issue).

PMID- 25598280
TI  - Commentary: Intermittent teriparatide enhancement of bone graft healing in a rat
      model of spinal glucocorticoid-induced osteoporosis.
AB  - COMMENTARY ON: Sugiura T, Kashii M, Matsuo Y, Morimoto T, Honda H, Kaito T, et
      al. Intermittent administration of teriparatide enhances graft bone healing and
      accelerates spinal fusion in rats with glucocorticoid-induced osteoporosis. Spine
      J 2015;15:298-306 (in this issue).

PMID- 25598281
TI  - Re: Berg S, Tullberg T. Letter to the editor regarding Mannion, Brox, Fairbank.
      Comparison of spinal fusion and nonoperative treatment in patients with chronic
      low back pain: long-term follow-up of three randomized controlled trials. Spine J
      2014;14:1087.

PMID- 25598282
TI  - Reply to letter to the editor from Berg S, Tullberg T. Letter to the editor
      regarding Mannion, Brox, Fairbank. Comparison of spinal fusion and nonoperative
      treatment in patients with chronic low back pain: long-term follow-up of three
      randomized controlled trials. Spine J 2014;14:1087.

PMID- 25598283
TI  - Isoform-specific imprinting of the MEST gene in porcine parthenogenetic fetuses.
AB  - Aberrant expression of imprinted genes is the main reason for developmental
      retardation in mammalian parthenogenetic fetuses. Mesoderm specific transcript
      (MEST) is a maternally imprinted gene that is linked to cancer and is necessary
      for normal early embryonic development. Tissue and isoform-specific imprinting of
      MEST have been identified in humans and mice, but have not yet been identified in
      pigs. In this study, the three isoforms of porcine MEST were identified using the
      GenBank and Ensembl sequence databases. Then, we determined MEST isoform-specific
      mRNA expression and methylation levels by quantitative real-time PCR (qRT-PCR)
      and bisulfite sequencing PCR analysis (BSP) between porcine parthenogenetic (PA)
      and control (Con) fetuses, respectively. Altogether, our results demonstrated
      that the expression of MEST-1A and MEST-1B has no evident differences between PA
      and Con groups; however, there is no expression of MEST-1C in PA fetuses. In
      addition, the results of BSP showed that the hypermethylation of exon 1c of MEST
      1C was observed in PA samples. Thus, we suggested that MEST-1C was isoform
      specific imprinting, which may be contributed to differential methylation status
      of exon 1c in porcine fetuses. 

PMID- 25598284
TI  - MAR characteristic motifs mediate episomal vector in CHO cells.
AB  - An ideal gene therapy vector should enable persistent transgene expression
      without limitations in safety and reproducibility. Recent researches' insight
      into the ability of chromosomal matrix attachment regions (MARs) to mediate
      episomal maintenance of genetic elements allowed the development of a circular
      episomal vector. Although a MAR-mediated engineered vector has been developed,
      little is known on which motifs of MAR confer this function during interaction
      with the host genome. Here, we report an artificially synthesized DNA fragment
      containing only characteristic motif sequences that served as an alternative to
      human beta-interferon matrix attachment region sequence. The potential of the
      vector to mediate gene transfer in CHO cells was investigated. The short
      synthetic MAR motifs were found to mediate episomal vector at a low copy number
      for many generations without integration into the host genome. Higher transgene
      expression was maintained for at least 4 months. In addition, MAR was maintained
      episomally and conferred sustained EGFP expression even in nonselective CHO
      cells. All the results demonstrated that MAR characteristic sequence-based vector
      can function as stable episomes in CHO cells, supporting long-term and effective
      transgene expression.

PMID- 25598285
TI  - Comparison of eleven commercially available rapid tests for detection of Bacillus
      anthracis, Francisella tularensis and Yersinia pestis.
AB  - Yersinia pestis, Bacillus anthracis and Francisella tularensis cause serious
      zoonotic diseases and have the potential to cause high morbidity and mortality in
      humans. In case of natural outbreaks and deliberate or accidental release of
      these pathogens rapid detection of the bacteria is crucial for limitation of
      negative effects of the release. In the present study, we evaluated 11
      commercially available rapid test kits for the detection of Y. pestis, B.
      anthracis and F. tularensis in terms of sensitivity, specificity and simplicity
      of the procedure. The results revealed that rapid and easy-to-perform lateral
      flow assays for detection of highly pathogenic bacteria have very limited
      sensitivity. In contrast, the immunofiltration assays showed high sensitivity but
      limited specificity and required a too complicated procedure to be applied in the
      field by nonlaboratory workers (e.g. First Responders like fire, police and
      emergency medical personnel). Each sample - whether tested negative or positive
      by the rapid tests - should be retested in a reference laboratory using validated
      methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid detection of highly
      pathogenic bacteria causing anthrax, plague and tularemia is crucial for the
      limitation of negative effects of a potential release (natural, accidental or
      deliberate). In the study, commercially available rapid tests for detection of
      Bacillus anthracis, Yersinia pestis and Francisella tularensis were investigated
      in terms of sensitivity, specificity and ease-to-perform. The study showed
      problems which could be faced during testing and results interpretation.
      Conclusions from this study should be helpful not only in selection of the most
      appropriate test for particular group of First Responders but also in undertaking
      decisions in situation of a contamination suspicion which have high social and
      economical impacts.

PMID- 25598286
TI  - Incidence of ultrasound-detected asymptomatic long-term central vein catheter
      related thrombosis and fibrin sheath in cancer patients.
AB  - BACKGROUND: Most central venous catheter (CVC)-related deep vein thromboses (DVT)
      are asymptomatic and their incidence and clinical relevance are still under
      debate. Data on CVC-related fibrin sheaths are scarce. We investigated the
      incidence of asymptomatic DVT and fibrin sheaths in cancer patients with long
      term CVC implantation who underwent Doppler ultrasound surveillance at 1, 6, and
      12 months after implantation. Effects of low-weight molecular heparin (LWMH)
      therapy on DVT and fibrin sheaths were also analyzed. MATERIAL AND METHODS: This
      prospective study was performed on a large cohort (n = 400) of patients with
      cancer aged >18 requiring long-term CVC implantation for chemotherapy infusion.
      CVC was implanted by a trained qualified staff, according to standardized
      protocol in a specific surgery. Patients underwent ultrasound examination at 1
      and 6 months after CVC implantation to detect 'early' (1 month) and 'late' (6
      months) asymptomatic DVT or fibrin sheaths incidence. Sixty-nine patients
      underwent US examination also 12 months after CVC implantation. RESULTS: The
      incidence of CVC-related thrombosis was 0.10 events per 1000 catheter days.
      Anticoagulation therapy with LWMH resolved 50% of DVT, but no CVC needed
      removing. Incidence of new onset fibrin sheaths was 0.71 events per 1000 catheter
      days. Fibrin sheaths resolution occurred independently of LWMH therapy.
      DISCUSSION: The incidence of asymptomatic DVT in our patients with long-term CVC
      is very low and does not represent per se an indication for removal of
      functioning CVC in patients with cancer. Fibrin sheaths are frequent (13%) and
      never associated with CVC dysfunction. CONCLUSION: Asymptomatic DVT and fibrin
      sheaths do not represent per se an indication for removal of functioning CVC in
      cancer patients who need central vein access.

PMID- 25598287
TI  - Manic patients exhibit more utilitarian moral judgments in comparison with
      euthymic bipolar and healthy persons.
AB  - Both emotional and cognitive processes are involved in moral judgments.
      Ventromedial prefrontal lesions are related to impaired prosocial emotions and
      emotional dysregulation, and patients with these lesions exhibit increased
      utilitarian judgments of emotionally salient personal moral dilemmas. Bipolar
      patients experiencing manic episode also have impaired emotional regulation and
      behavioral control. We investigated the characteristics of moral judgment in
      manic and euthymic patients with bipolar disorder using the 50 hypothetical moral
      dilemma task (17 non-moral, 20 personal, and 13 impersonal). Our study included
      27 manic bipolar patients, 26 euthymic bipolar patients, and 42 healthy controls.
      Subjects were instructed to determine whether or not each dilemma was morally
      acceptable, and their reaction times were recorded. Manic patients showed
      significantly greater utilitarian judgment than euthymic patients and normal
      controls for personal moral dilemmas. However, there were no significant between
      group differences for the non-moral and impersonal moral dilemmas. Our results
      suggest that increased utilitarian judgments of personal moral dilemmas may be a
      state-related finding observed only in manic patients. This difference in moral
      judgment assessments may reflect the decision-making characteristics and
      underlying neurobiological mechanisms of bipolar disorder, especially during the
      manic state. 

PMID- 25598288
TI  - Psychometric properties of the self-reporting questionnaire (SRQ-20): measurement
      invariance across women from Brazilian community settings.
AB  - BACKGROUND: SRQ-20 is a validated screening tool for common psychiatric disorders
      in several countries. Exploration of the latent structure of this instrument
      resulted in conflicting evidence. This study aimed to explore the latent
      structure of SRQ-20 among Brazilian women from community settings. We also tested
      the model invariance across different sociodemographic conditions. METHODS:
      Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were
      conducted on a sample of 1668 women from four different geographical regions of
      Brazil. Invariance of the model was tested through multi-group CFA according to
      sociodemographic variables. RESULTS: EFA has shown two potential solutions with
      two and three factors. CFA resulted in indices of the two-factor solution
      slightly worse than the three-factor solution. Invariance testing has shown this
      model was not invariant across cities, but was invariant across different social
      classes. The structure was also invariant for the two lower educated groups. The
      respecified model (i.e., excluding item 16) was not invariant across groups with
      different educational levels. CONCLUSION: The three-factor solution seems to be
      the most suitable model of SRQ-20 for Brazilian women in community settings.
      Furthermore, sociodemographic variables seem to reflect on the latent structure
      of this instrument. Validation of screening tools should consider
      sociodemographic variables.

PMID- 25598290
TI  - The effect of height and BMI on computer dynamic posturography parameters in
      women.
AB  - The human body's posture control is a complex system of organs and mechanisms
      which controls the body's centre of gravity (COG) over its base of support (BOS).
      Computerised Dynamic Posturography (CDP) allows for the quantitative and
      objective assessment of the sensory and motor components of the body's posture
      control system as well as of the integration and adaptation mechanisms in the
      central nervous system. The aim of this study was to assess the relationships
      between the body's height and BMI on CDP results in a group of young healthy
      women without any clinical symptoms of balance disorders. It was found that the
      MS depended significantly on the height and BMI of the subjects as well as on the
      SOT conditions. As the height and BMI increased the MS value decreased. The
      postural response latency (LC) in the MCT statistically significantly depended
      only on height and showed a positive correlation. The postural response latency
      increased with height. The postural response amplitude for both right and left
      lower limbs significantly depended on height and BMI, but only for the backward
      movement of the platform. The response amplitude for all platform translations
      under all MCT conditions increased with height and BMI. The body's resultant
      imbalance caused by the platform perturbations in the ADT was greater in shorter
      people and those with a lower BMI. 

PMID- 25598289
TI  - Molecular Typing of Bluetongue Viruses Isolated Over a Decade in South India.
AB  - Bluetongue (BT) is an arthropod-borne viral disease mostly of sheep. Bluetongue
      virus (BTV) is a segmented double-stranded RNA virus belonging to the genus
      Orbivirus of family Reoviridae and is transmitted by midges belonging to
      Culicoides spp. The disease is endemic in the tropics and subtropics, and the
      incidence is high in southern India. Twenty-six serotypes of BTV have been
      reported worldwide. Although most of the serotypes have been reported in India,
      information regarding currently circulating serotypes is essential to develop
      control programs. Both serological assays and nucleic acid-based assays have been
      used for typing BTV. Segment 2, which codes for the outer capsid protein VP2, is
      the target for PCR-based typing; however, the VP2 sequence diversity among
      viruses belonging to the same serotype but isolated from different geographical
      areas makes it essential to develop geographical based reagents. In this study,
      reverse transcription PCR was developed based on sequences of Indian isolates of
      BTV (serotypes 1, 2, 9, 10, 12, 16, 21 and 23), and this was applied to type 52
      isolates obtained during the last decade. It was found that multiple serotypes
      circulate, with involvement of more than one serotype infecting individual
      animals and herds over a period in a given area. Detection of circulating
      serotypes and estimation of herd immunity against different serotypes of BTV may
      provide important information for predicting the distribution of these serotypes
      and inclusion of serotypes in vaccines. 

PMID- 25598291
TI  - Expression and effects of B-lymphocyte stimulator and its receptors in T cell
      mediated autoimmune arthritis.
AB  - The objective of this study was to determine the expression and effects of B
      lymphocyte stimulator (BLyS) in T cell-mediated autoimmune arthritis, a rat model
      of human rheumatoid arthritis (RA). Rat adjuvant-induced arthritis (AA) was
      induced by intradermal injection of 0.1ml complete Freund's adjuvant. Arthritis
      was evaluated by the histopathological examination of joint ankle. The BLyS
      expression was detected by immunohistochemical analysis. The level of BLyS and
      interleukin (IL)-17 were assayed by enzyme-linked immunosorbent assay. The gene
      expression of BLyS and its receptors (TACI, BCMA and BAFF-R) were assessed by
      quantitative reverse-transcription polymerase chain reaction. The effect of BLyS
      on the function of T cell was investigated by transwell assay. Using an AA rat
      model, we detected dysregulated expression and level of BLyS and its receptors in
      the local joint synovium tissue, peripheral lymphoid organs (spleen) and immune
      cells (macrophage, dendritic cells (DC) and T cell) at the peak of inflammation.
      In vitro, BLyS-treated DC induced IL-17 producing T cells. Neutralization of BLyS
      by the TACI-Ig fusion protein attenuated these stimulating effects of BLyS. These
      data suggest that the overproduction of BLyS may contribute to T cell responses
      and may be an attractive target for control of autoimmune diseases, such as RA,
      that involves both T and B cells. 

PMID- 25598292
TI  - Enalapril treatment increases T cell number and promotes polarization towards M1
      like macrophages locally in diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a serious complication of longstanding diabetes
      affecting up to 30% of all diabetes patients and is the main cause of end-stage
      kidney disease globally. Current standard treatment e.g. ACE-inhibitors like
      enalapril merely offers a delay in the progression leading to DN. Herein, we
      describe in two preclinical models evidence to local effects on the inflammatory
      signatures after intervention treatment with enalapril which provides enhanced
      understanding of the mechanism of ACE inhibitors. Enalapril transiently reduced
      albuminuria in both the db/db and the STZ-induced DN models with established
      disease, without modulating the HbA1c%. Albuminuria was strongly associated with
      loss of leukocytes, particularly B cells, but also of sub-populations of
      macrophages and CD4(+) T cells. The remaining kidney macrophages were polarized
      into a M2-like sub-population with reduced surface expression of the M1-like
      macrophage marker CD11c and enhanced expression of galectin-3. Enalapril
      treatment counteracted the reduction of leukocytes in the diabetic kidney towards
      levels noted in the non-diabetic kidney. Particularly, a subset of macrophages
      was increased and a clear expansion of CD4(+) and CD8(+) T cells was observed.
      However, enalapril failed to modulate the B cell compartment. Interestingly,
      enalapril treatment resulted in a re-polarization of the macrophages towards a M1
      like phenotype characterized by elevated levels of CD11c with moderate down
      regulation of the M2 marker galectin-3. The data demonstrate that ACE inhibition
      in pre-clinical models of DN shows a transient beneficial effect on albuminuria
      which is unexpectedly associated with restoration of T cells and M1-like
      macrophages in the kidney. 

PMID- 25598293
TI  - Safe mechanical ventilation in patients without acute respiratory distress
      syndrome (ARDS).
AB  - Insights into the pathogenesis of lung deformation injury inspired a benchmark
      clinical trial, which demonstrated that reducing tidal volumes compared to
      previous norms was associated with improved patient survival in acute respiratory
      distress syndrome (ARDS). Since many critically ill patients without ARDS possess
      ventilator associated lung injury (VALI) risk factors, there is no need to expose
      them to tidal volumes that are larger than would be needed to achieve acceptable
      blood gas tensions. In the following perspective we will argue that lung
      protection from deformation injury should guide ventilator management in all
      patients, irrespective of the presence of ARDS. That is not to say that all lung
      diseases share the same VALI risk, but we contend that adopting a low tidal
      ventilation strategy is a simple and safe starting point in most instances. We
      will review studies in the medical and surgical literature that have addressed
      "lung protective ventilation" in patients without ARDS and summarize them with a
      focus on tidal volume, positive end expiratory pressure and oxygen
      supplementation settings. In addition, we will briefly discuss under what
      circumstance one might consider deviating from a conventional approach. 

PMID- 25598294
TI  - Navigator(r) and SmartPilot(r) View are helpful in guiding anesthesia and
      reducing anesthetic drug dosing.
AB  - BACKGROUND: The recently introduced Navigator(r) (GE Healthcare, Helsinki,
      Finland) and SmartPilot(r) View (Drager Medical, Lubeck, Germany) show the
      concentrations and predicted effects of combined anesthetic drugs, and should
      facilitate more precisely their titration. Our aim was to evaluate if
      Navigator(r) or SmartPilot(r) View guided anesthesia was associated with a good
      quality of analgesia, depth of hypnosis and may reduce anesthetic requirements.
      METHODS: We performed a prospective non-randomized study. Sixty ASA I-II patients
      undergoing balanced general anesthesia for abdominal and plastic surgery were
      enrolled. Patients were divided in 4 groups. Group 1 (N. 15) and group 3 (N. 15)
      were cases in whom anesthesia was performed with standard monitoring plus the aid
      of Navigator(r) (Nav) or SmartPilot(r) View (SPV) display. Group 2 (N. 15) and
      group 4 (N. 15) were controls in whom anesthesia was performed with standard
      monitoring (heart rate, NIBP, SpO2, end-tidal CO2, end-expired sevoflurane
      concentration, train of four, Bispectral Index [Aspect Medical Systems, Natick,
      MA, USA] or Entropy [GE Healthcare]). Patients' vital parameters and end-expired
      sevoflurane concentration were recorded during anesthesia. RESULTS: All patients
      recovered uneventfully and showed hemodynamic stability. End-tidal sevoflurane
      concentrations values [median (min-max)], during maintenance of anesthesia, were
      significantly (P<0.05) lower in SPV [1.1% (0.8-1.5)] and Nav [1%(0.8-1.8)] groups
      compared to SPV-control group [1.5%(1-2.5)] and Nav-control group [1.5%(0.8-2)].
      BIS and entropy values were respectively higher in the SPV group [53 (46-57)]
      compared to the control group [43 (37-51)] (P<0.05) and Nav group [53 (43-60)]
      compared to the control group [41 (35-51)] (P<0.05). No significant differences
      in Remifentanil dosing were observed in the four groups. CONCLUSION: Navigator(r)
      and SmartPilot(r) View may be of clinical use in monitoring adequacy of
      anesthesia. Both displays can optimize the administration and monitoring of
      anesthetic drugs during general anesthesia and may reduce the consumption of
      volatile anesthetic agents.

PMID- 25598295
TI  - Non-invasive assessment of ARDS lung elastance: still have not found what we are
      looking for.

PMID- 25598296
TI  - Do we always do the "right" thing? The influence of cultural aspects on ICU work
      and organization.

PMID- 25598297
TI  - Selective digestive decontamination: a pre-emptive treatment for a few European
      ecological niches or a worldwide implementation?

PMID- 25598298
TI  - Missed citations.

PMID- 25598299
TI  - Reply: To PMID 25212123.

PMID- 25598301
TI  - Silver catalysed decarboxylative alkylation and acylation of pyrimidines in
      aqueous media.
AB  - Decarboxylative alkylation or acylation reactions of simple pyrimidines have been
      developed in aqueous media. Using aliphatic carboxylic acids or 2-oxocarboxylic
      acids and pyrimidines as substrates and silver as the catalyst, the 4-substituted
      alkyl or acyl pyrimidines were isolated in moderate to good yields. 

PMID- 25598302
TI  - A closer look at the apparent correlation of structural and functional
      connectivity in excitable neural networks.
AB  - The relationship between the structural connectivity (SC) and functional
      connectivity (FC) of neural systems is a central focus in brain network science.
      It is an open question, however, how strongly the SC-FC relationship depends on
      specific topological features of brain networks or the models used for describing
      excitable dynamics. Using a basic model of discrete excitable units that follow a
      susceptible - excited - refractory dynamic cycle (SER model), we here analyze how
      functional connectivity is shaped by the topological features of a neural
      network, in particular its modularity. We compared the results obtained by the
      SER model with corresponding simulations by another well established dynamic
      mechanism, the Fitzhugh-Nagumo model, in order to explore general features of the
      SC-FC relationship. We showed that apparent discrepancies between the results
      produced by the two models can be resolved by adjusting the time window of
      integration of co-activations from which the FC is derived, providing a clearer
      distinction between co-activations and sequential activations. Thus, network
      modularity appears as an important factor shaping the FC-SC relationship across
      different dynamic models. 

PMID- 25598303
TI  - Developmental trajectories of young children with neurofibromatosis type 1: a
      longitudinal study from 21 to 40 months of age.
AB  - OBJECTIVE: To establish the developmental trajectory of young children with
      neurofibromatosis type 1 (NF1) during the first 4 years of life. STUDY DESIGN: In
      this longitudinal study, 39 children with NF1 and 39 controls were assessed with
      the Bayley Scales of Infant Development, Second Edition at 21 (time point 1, or
      T1) and 30 months (T2) of age, and the Wechsler Preschool and Primary Scale of
      Intelligence, Third Edition at 40 months (T3). Language was also assessed at T2
      and T3. Parents rated their child's productive vocabulary at T1 and T2, and
      behavior at each time point. Linear mixed models were performed to examine
      cognitive development and behavior over time. Linear regressions were conducted
      to determine whether mental development and productive vocabulary at T1 or T2
      predicted intellectual and language outcomes at T3. RESULTS: Over time, the NF1
      group had significantly lower cognitive scores than controls. Parent ratings
      indicated no group differences in behavior at each time point. Earlier mental
      function significantly predicted later general intelligence. Earlier productive
      vocabulary was a significant predictor of later language skills. CONCLUSIONS:
      There are consistent differences over time in cognitive performance between
      children with NF1 and unaffected peers during the early childhood period. Earlier
      mental function and productive vocabulary are significant predictors of
      subsequent general intelligence and performance on language measures in NF1. This
      provides an opportunity for early identification and treatment for young children
      with NF1 who may show signs of impairments in these developmental domains.

PMID- 25598304
TI  - Disruptive behavior in preschool children: distinguishing normal misbehavior from
      markers of current and later childhood conduct disorder.
AB  - OBJECTIVES: To investigate which disruptive behaviors in preschool were normative
      and transient vs markers of conduct disorder, as well as which disruptive
      behaviors predicted the persistence of conduct disorder into school age. STUDY
      DESIGN: Data from a longitudinal study of preschool children were used to
      investigate disruptive behaviors. Caregivers of preschoolers ages 3.0-5.11 years
      (n = 273) were interviewed using the Preschool Age Psychiatric Assessment to
      derive the following diagnostic groups: conduct disorder, externalizing disorder
      without conduct disorder, internalizing disorder without externalizing disorder,
      and healthy. At school age, participants were again assessed via an age
      appropriate diagnostic interview. Logistic and linear regression with pairwise
      group comparisons was used to investigate clinical markers of preschool conduct
      disorder and predictors of school age conduct disorder. RESULTS: Losing one's
      temper, low-intensity destruction of property, and low-intensity
      deceitfulness/stealing in the preschool period were found in both healthy and
      disordered groups. In contrast, high-intensity argument/defiant behavior, both
      low- and high-intensity aggression to people/animals, high-intensity destruction
      of property, high-intensity deceitfulness/stealing, and high-intensity peer
      problems were markers of preschool conduct disorder and predictors of school age
      conduct disorder. Inappropriate sexual behavior was not a marker for preschool
      conduct disorder but was a predictor of school age conduct disorder. CONCLUSION:
      These findings provide a guide for primary care clinicians to help identify
      preschoolers with clinical conduct disorder and those who are at risk for
      persistent conduct disorder in childhood. Preschoolers displaying these symptoms
      should be targeted for mental health assessment.

PMID- 25598305
TI  - Academic Performance among Children with Inflammatory Bowel Disease: A Population
      Based Study.
AB  - OBJECTIVES: To determine grade 12 academic performance for children with
      inflammatory bowel disease (IBD). STUDY DESIGN: Children diagnosed with IBD at
      age<17 years identified from the population-based University of Manitoba IBD
      Epidemiology Database were matched by age-, sex-, and area of residence to 10
      randomly selected controls. Grade 12 educational outcomes (scores on the
      provincial grade 12 language arts and mathematics standards tests, and enrollment
      in-grade-12-by- age-17) were determined by linkage to the province wide Manitoba
      Education Database. Linear and logistic regression analysis were used to compare
      the educational outcomes, adjusting for socioeconomic status and comorbidities
      and evaluate predictors of educational outcomes among children with IBD. RESULTS:
      Grade 12 educational outcomes among 337 children with IBD were compared with 3093
      without IBD. There were no significant differences among the 2 groups in the
      standardized scores (language arts: P=.31; mathematics: P=.48) or enrollment-in
      grade-12-by- age-17 (P=.25). Lower socioeconomic status and diagnosis with mental
      health problems 6 months prior to and 6 months post-IBD diagnosis were
      independent predictors of worse educational outcomes. There was no significant
      effect of age of diagnosis of IBD, type of IBD (ulcerative colitis vs Crohn's
      disease), use of corticosteroids or immunomodulator agents, hospitalizations, or
      surgery for IBD. CONCLUSIONS: Children with IBD on average achieve similar levels
      of academic achievement in grade 12 as those without IBD. This study underscores
      the educational impact of mental health conditions at IBD diagnosis among
      children.

PMID- 25598306
TI  - Adverse events following Haemophilus influenzae type b vaccines in the Vaccine
      Adverse Event Reporting System, 1990-2013.
AB  - OBJECTIVE: To characterize adverse events (AEs) after Haemophilus influenzae type
      b (Hib) vaccines reported to the US Vaccine Adverse Event Reporting System
      (VAERS), a spontaneous reporting surveillance system. STUDY DESIGN: We searched
      VAERS for US reports after Hib vaccines among reports received from January 1,
      1990, to December 1, 2013. We reviewed a random sample of reports and
      accompanying medical records for reports classified as serious. All reports of
      death were reviewed. Physicians assigned a primary clinical category to each
      reviewed report. We used empirical Bayesian data mining to identify AEs that were
      disproportionally reported after Hib vaccines. RESULTS: VAERS received 29,747
      reports after Hib vaccines; 5179 (17%) were serious, including 896 reports of
      deaths. Median age was 6 months (range 0-1022 months). Sudden infant death
      syndrome was the stated cause of death in 384 (51%) of 749 death reports with
      autopsy/death certificate records. The most common nondeath serious AE categories
      were neurologic (80; 37%), other noninfectious (46; 22%) (comprising mainly
      constitutional signs and symptoms); and gastrointestinal (39; 18%) conditions. No
      new safety concerns were identified after clinical review of reports of AEs that
      exceeded the data mining statistical threshold. CONCLUSION: Review of VAERS
      reports did not identify any new or unexpected safety concerns for Hib vaccines.

PMID- 25598307
TI  - Dual-gated MoS2/WSe2 van der Waals tunnel diodes and transistors.
AB  - Two-dimensional layered semiconductors present a promising material platform for
      band-to-band-tunneling devices given their homogeneous band edge steepness due to
      their atomically flat thickness. Here, we experimentally demonstrate interlayer
      band-to-band tunneling in vertical MoS2/WSe2 van der Waals (vdW) heterostructures
      using a dual-gate device architecture. The electric potential and carrier
      concentration of MoS2 and WSe2 layers are independently controlled by the two
      symmetric gates. The same device can be gate modulated to behave as either an
      Esaki diode with negative differential resistance, a backward diode with large
      reverse bias tunneling current, or a forward rectifying diode with low reverse
      bias current. Notably, a high gate coupling efficiency of ~80% is obtained for
      tuning the interlayer band alignments, arising from weak electrostatic screening
      by the atomically thin layers. This work presents an advance in the fundamental
      understanding of the interlayer coupling and electron tunneling in semiconductor
      vdW heterostructures with important implications toward the design of atomically
      thin tunnel transistors. 

PMID- 25598310
TI  - Three new solvent-directed Cd(II)-based MOFs with unique luminescent properties
      and highly selective sensors for Cu(2+) cations and nitrobenzene.
AB  - Three new solvent-induced metal-organic frameworks (MOFs)-[Cd(H2L)(H2O)3].NMP (),
      [Cd3(L)(H2O)4(OH)2] () and [Cd(L)0.5(H2O)].H2O ()-were designed and successfully
      prepared via solvothermal reaction by multidentate phenyltetracarboxylic acid
      [1,1':4',1''-terphenyl]-2',3,3'',5'-tetracarboxylic acid (H4L) and Cd(ii) salts
      in various solvent systems. Structural analyses indicated that the H2L/L ligands
      took three different coordination fashions in , and thus resulted in diversity of
      the targeted MOFs. Solid-state luminescent properties of the three MOFs were
      studied under ultraviolet light irradiation at ambient temperature; in particular
      showed high selectivity and sensitivity for Cu(2+) ions and nitrobenzene because
      of the quenching effect, which thus could make it a potential crystalline
      material for detecting these substances. The mechanisms of the quenching effect
      and sensing properties of are discussed in detail. 

PMID- 25598309
TI  - Copper-obatoclax derivative complexes mediate DNA cleavage and exhibit anti
      cancer effects in hepatocellular carcinoma.
AB  - Obatoclax is an indole-pyrrole compound that induces cancer cell apoptosis
      through targeting the anti-apoptotic Bcl-2 protein family. Previously, we
      developed a series of obatoclax derivatives and studied their STAT3 inhibition
      dependent activity against cancer cell lines. The obatoclax analog, prodigiosin,
      has been reported to mediate DNA cleavage in cancer cells by coordinating with
      copper complexes. To gain an understanding of copper-obatoclax complex activity,
      we applied obatoclax derivatives to examine their copper-mediated nuclease
      activity as a means to establish a basis for structure activity relationship.
      Replacement of the indole ring of obatoclax with furanyl, thiophenyl or Boc
      indolyl rings reduced the DNA cleavage ability. The same effect was achieved
      through the replacement of the obatoclax pyrrolyl ring with thiazolidinedione and
      thioacetal. Among the compounds tested, we demonstrated that the complex of
      obatoclax or compound 7 with copper exhibited potent DNA strand scission which
      correlated with HCC cell growth inhibition. 

PMID- 25598311
TI  - Stable metal-organic frameworks containing single-molecule traps for enzyme
      encapsulation.
AB  - Enzymatic catalytic processes possess great potential in chemical manufacturing,
      including pharmaceuticals, fuel production and food processing. However, the
      engineering of enzymes is severely hampered due to their low operational
      stability and difficulty of reuse. Here, we develop a series of stable metal
      organic frameworks with rationally designed ultra-large mesoporous cages as
      single-molecule traps (SMTs) for enzyme encapsulation. With a high concentration
      of mesoporous cages as SMTs, PCN-333(Al) encapsulates three enzymes with record
      high loadings and recyclability. Immobilized enzymes that most likely undergo
      single-enzyme encapsulation (SEE) show smaller Km than free enzymes while
      maintaining comparable catalytic efficiency. Under harsh conditions, the enzyme
      in SEE exhibits better performance than free enzyme, showing the effectiveness of
      SEE in preventing enzyme aggregation or denaturation. With extraordinarily large
      pore size and excellent chemical stability, PCN-333 may be of interest not only
      for enzyme encapsulation, but also for entrapment of other nanoscaled functional
      moieties. 

PMID- 25598312
TI  - Magnetic C-C@Fe3O4 double-shelled hollow microspheres via aerosol-based Fe3O4@C
      SiO2 core-shell particles.
AB  - Magnetic C-C@Fe3O4 hollow microspheres were prepared by using aerosol-based
      Fe3O4@C-SiO2 core-shell particles as templates. The magnetic double-shelled
      microspheres efficiently worked as carriers to load Pt nanoparticles, thus making
      the catalyst recyclable and reusable. 

PMID- 25598313
TI  - Natalizumab discontinuation and disease restart in pregnancy: a case series.
AB  - BACKGROUND: The humanized monoclonal alpha4-integrin antibody Natalizumab (NTZ)
      (Tysabri((c)) , Biogen Idec, Cambridge, MA, USA) has shown to be effective in
      multiple sclerosis (MS) therapy; however, the interruption of the drug has been
      related to a disease restart. This risk has to be carefully considered in case of
      accidental or desired pregnancies. AIM OF THE STUDY: To report the risk of
      disease restart in patients who interrupted NTZ because of pregnancy and discuss
      the implication of NTZ choice in female childbearing patients with MS. METHODS:
      Clinical histories and MRI images of four pregnant women with MS who interrupted
      NTZ. RESULTS: Despite pregnancy is usually related with disease stability, the
      cases presented here showed an abrupt increase of disability with high number of
      MRI lesions, some of them with a mass effect. CONCLUSIONS: We recommend that
      female patients on childbearing age must be informed before starting NTZ
      treatment of the risk of a return of disease activity when the drug is
      discontinued. The risk occurs even during pregnancy a condition that is
      considered as protective for women with MS.

PMID- 25598308
TI  - Microfluidic cell sorting: a review of the advances in the separation of cells
      from debulking to rare cell isolation.
AB  - Accurate and high throughput cell sorting is a critical enabling technology in
      molecular and cellular biology, biotechnology, and medicine. While conventional
      methods can provide high efficiency sorting in short timescales, advances in
      microfluidics have enabled the realization of miniaturized devices offering
      similar capabilities that exploit a variety of physical principles. We classify
      these technologies as either active or passive. Active systems generally use
      external fields (e.g., acoustic, electric, magnetic, and optical) to impose
      forces to displace cells for sorting, whereas passive systems use inertial
      forces, filters, and adhesion mechanisms to purify cell populations. Cell sorting
      on microchips provides numerous advantages over conventional methods by reducing
      the size of necessary equipment, eliminating potentially biohazardous aerosols,
      and simplifying the complex protocols commonly associated with cell sorting.
      Additionally, microchip devices are well suited for parallelization, enabling
      complete lab-on-a-chip devices for cellular isolation, analysis, and experimental
      processing. In this review, we examine the breadth of microfluidic cell sorting
      technologies, while focusing on those that offer the greatest potential for
      translation into clinical and industrial practice and that offer multiple, useful
      functions. We organize these sorting technologies by the type of cell preparation
      required (i.e., fluorescent label-based sorting, bead-based sorting, and label
      free sorting) as well as by the physical principles underlying each sorting
      mechanism. 

PMID- 25598314
TI  - Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive
      control during task switching performance.
AB  - Tyrosine (TYR), an amino acid found in various foods, has been shown to increase
      dopamine (DA) levels in the brain. Recent studies have provided evidence that TYR
      supplementation can improve facets of cognitive control in situations with high
      cognitive demands. Here we investigated whether TYR promotes cognitive
      flexibility, a cognitive-control function that is assumed to be modulated by DA.
      We tested the effect of TYR on proactive vs. reactive control during task
      switching performance, which provides a relatively well-established diagnostic of
      cognitive flexibility. In a double-blind, randomized, placebo-controlled design,
      22 healthy adults performed in a task-switching paradigm. Compared to a neutral
      placebo, TYR promoted cognitive flexibility (i.e. reduced switching costs). This
      finding supports the idea that TYR can facilitate cognitive flexibility by
      repleting cognitive resources. 

PMID- 25598315
TI  - Complex brain network properties in late L2 learners and native speakers.
AB  - Whether the neural mechanisms that underlie the processing of a second language
      in highly proficient late bilinguals (L2 late learners) are similar or not to
      those that underlie the processing of the first language (L1) is still an issue
      under debate. In this study, a group of late learners of Spanish whose native
      language is English and a group of Spanish monolinguals were compared while they
      read sentences, some of which contained syntactic violations. A brain complex
      network analysis approach was used to assess the time-varying topological
      properties of the functional networks extracted from the electroencephalography
      (EEG) recording. Late L2 learners showed a lower degree of parallel information
      transfer and a slower propagation between regions of the brain functional
      networks while processing sentences containing a gender mismatch condition as
      compared with a standard sentence configuration. In contrast, no such differences
      between these conditions were detected in the Spanish monolinguals. This
      indicates that when a morphosyntactic language incongruence that does not exist
      in the native language is presented in the second language, the neural activation
      pattern is configured differently in highly proficient late bilinguals than in
      monolinguals.

PMID- 25598317
TI  - An embryonic heart cell line is susceptible to dengue virus infection.
AB  - Dengue virus (DENV) is the causative agent of dengue fever. In recent years,
      patients with more severe form of the disease with acute heart failure or
      progression to cardiogenic shock and death have been reported. However, the
      pathogenesis of myocardial lesions and susceptibility of cardiomyocytes to DENV
      infection have not been evaluated. Under this perspective, the susceptibility of
      the myoblast cell line H9c2, obtained from embryonic rat heart, to DENV infection
      was analyzed. Our findings indicate that H9c2 cells are susceptible to the
      infection with the four DENV serotypes. Moreover, virus translation/replication
      and viral production in this cell line is as efficient as in other susceptible
      cell lines, supporting the idea that DENV may target heart cells as evidenced by
      infection of H9c2 cells. This cell line may thus represent an excellent model for
      the study and characterization of cardiac physiopathology in DENV infection. 

PMID- 25598316
TI  - Sublinear response in lacZ mutant frequency of MutaTM Mouse spermatogonial stem
      cells after low dose subchronic exposure to N-ethyl-N-nitrosourea.
AB  - The transgenic rodent mutation assay was used to compare the dose-response
      relationship of lacZ mutant frequency (MF) in spermatogonial stem cells exposed
      acutely or subchronically to N-ethyl-N-nitrosourea (ENU). Muta(TM) Mouse males
      were exposed orally to 0, 25, 50, or 100 mg/kg ENU for acute exposures and 0, 1,
      2, or 5 mg/(kg day) for 28-day subchronic exposures. LacZ MF was measured in
      sperm collected 70 days post-exposure to target spermatogonial stem cells. Dose
      response data were fit to linear, quadratic, exponential, or power models. Acute
      exposure resulted in a dose-dependent increase in MF that was significant (P <
      0.05) at all doses tested and was best described by a quadratic dose-response
      model that was linear in the low dose range. In contrast, similar total doses
      fragmented over a 28-day subchronic exposure only resulted in a significant
      increase in lacZ MF at the highest dose tested. Therefore, the subchronic no
      observable genotoxic effect level (NOGEL) was 2 mg/(kg day) (or 56 mg/kg total
      dose). The subchronic dose-response was best described by the exponential and
      power models, which were sublinear in the low dose range. Benchmark dose lower
      confidence limits (BMDLs) for acute and subchronic exposure were 3.0 and 1.0
      mg/(kg day) (or 27.4 mg/kg total dose), respectively. These findings are
      supportive of a saturable DNA repair mechanism as the mutagenic mode of action
      for ENU in spermatogonia and imply that sufficiently low exposures would not
      cause appreciable genotoxic effects over background. This may have important
      implications for the quantitative risk assessment of germ cell mutagens.

PMID- 25598318
TI  - The evolutionary reality of species and higher taxa in plants: a survey of post
      modern opinion and evidence.
AB  - Species are normally considered to be the fundamental unit for understanding the
      evolution of biodiversity. Yet, in a survey of botanists in 1940, twice as many
      felt that plant genera were more natural units than plant species. Revisiting the
      survey, we found more people now regarded species as a more evolutionarily real
      unit, but a sizeable number still felt that genera were more evolutionarily real
      than species. Definitions of 'evolutionarily real' split into those based on
      shared evolutionary history and those based on shared evolutionary fate via
      ongoing evolutionary processes. We discuss recent work testing for shared
      evolutionary fate at the species and higher levels and present preliminary
      evidence for evolutionarily significant higher taxa in plants.

PMID- 25598319
TI  - Regulation of skeletal muscle development and homeostasis by gene imprinting,
      histone acetylation and microRNA.
AB  - Epigenetics is defined as heritable information other than the DNA sequence
      itself. The concept implies that the regulation of gene expression is a highly
      complex process in which epigenetics plays a major role that ranges from fine
      tuning to permanent gene activation/deactivation. Skeletal muscle is the main
      tissue involved in locomotion and energy metabolism in the body, accounting for
      at least 40% of the body mass. Body mass and function vary according to age but
      also quickly adapt to both physiological and pathological cues. Besides
      transcriptional mechanisms that control muscle differentiation, postnatal growth
      and remodeling, there are numerous epigenetic mechanisms of regulation that
      modulate muscle gene expression. In this review, we describe and discuss only
      some of the mechanisms underlying epigenetic regulation, such as DNA methylation,
      histone modifications and microRNAs, which we believe are crucial to skeletal
      muscle development and disease. 

PMID- 25598320
TI  - Author's comments in response to letters by Tom Kindlon, Anna Sheridan and Robert
      Courtney.

PMID- 25598321
TI  - beta-elemene inhibited expression of DNA methyltransferase 1 through activation
      of ERK1/2 and AMPKalpha signalling pathways in human lung cancer cells: the role
      of Sp1.
AB  - beta-elemene, a compound derived from Rhizoma zedoariae, is a promising new plant
      derived drug with broad-spectrum anticancer activity. However, the underlying
      mechanism by which this agent inhibits human lung cancer cell growth has not been
      well elucidated. In this study, we showed that beta-elemene inhibits human non
      small cell lung carcinoma (NSCLC) cell growth, and increased phosphorylation of
      ERK1/2, Akt and AMPKalpha. Moreover, beta-elemene inhibited expression of DNA
      methyltransferase 1 (DNMT1), which was not observed in the presence of the
      specific inhibitors of ERK (PD98059) or AMPK (compound C). Overexpression of
      DNMT1 reversed the effect of beta-elemene on cell growth. Interestingly,
      metformin not only reversed the effect of beta-elemene on phosphorylation of Akt
      but also strengthened the beta-elemene-reduced DNMT1. In addition, beta-elemene
      suppressed Sp1 protein expression, which was eliminated by either ERK1/2 or AMPK
      inhibitor. Conversely, overexpression of Sp1 antagonized the effect of beta
      elemene on DNMT1 protein expression and cell growth. Taken together, our results
      show that beta-elemene inhibits NSCLC cell growth via ERK1/2- and AMPKalpha
      mediated inhibition of transcription factor Sp1, followed by reduction in DNMT1
      protein expression. Metformin augments the effect of beta-elemene by blockade of
      Akt signalling and additively inhibition of DNMT1 protein expression. The
      reciprocal ERK1/2 and AMPKalpha signalling pathways contribute to the overall
      responses of beta-elemene. This study reveals a potential novel mechanism by
      which beta-elemene inhibits growth of NSCLC cells. 

PMID- 25598322
TI  - Structural basis for the facilitative diffusion mechanism by SemiSWEET
      transporter.
AB  - SWEET family proteins mediate sugar transport across biological membranes and
      play crucial roles in plants and animals. The SWEETs and their bacterial
      homologues, the SemiSWEETs, are related to the PQ-loop family, which is
      characterized by highly conserved proline and glutamine residues (PQ-loop motif).
      Although the structures of the bacterial SemiSWEETs were recently reported, the
      conformational transition and the significance of the conserved motif in the
      transport cycle have remained elusive. Here we report crystal structures of
      SemiSWEET from Escherichia coli, in the both inward-open and outward-open states.
      A structural comparison revealed that SemiSWEET undergoes an intramolecular
      conformational change in each protomer. The conserved PQ-loop motif serves as a
      molecular hinge that enables the 'binder clip-like' motion of SemiSWEET. The
      present work provides the framework for understanding the overall transport
      cycles of SWEET and PQ-loop family proteins. 

PMID- 25598324
TI  - White matter lesions and temporal lobe atrophy related to incidence of both
      dementia and major depression in 70-year-olds followed over 10 years.
AB  - BACKGROUND AND PURPOSE: A number of studies have suggested associations between
      dementia and depression in older adults. One reason could be that these disorders
      share structural correlates, such as white matter lesions (WMLs) and cortical
      atrophy. No study has examined whether these lesions precede both dementia and
      depression independently of each other in the general population. METHODS:
      Whether WMLs and cortical atrophy on computed tomography predict dementia and
      depression was investigated in a population-based sample of 70-year-olds (n =
      380) followed over 10 years. Exclusion criteria were dementia, major depression,
      history of stroke and a Mini-Mental State Examination score below 26 at baseline
      in 2000-2001. Dementia was diagnosed according to the Diagnostic and Statistical
      Manual of Mental Disorders, third edition, revised, and depression according to
      the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Primary
      outcomes included dementia and major depression at 10-year follow-up. RESULTS:
      Adjusted logistic regression models, including both WMLs and temporal lobe
      atrophy, showed that moderate to severe WMLs [odds ratio (OR) 3.96, 95%
      confidence interval (CI) 1.23-12.76] and temporal lobe atrophy (OR 2.93, 95% CI
      1.13-7.60) predicted dementia during a 10-year follow-up independently of major
      depression. Similarly, both moderate to severe WMLs (OR 3.84, 95% CI 1.25-11.76)
      and temporal lobe atrophy (OR 2.52, 95% CI 1.06-5.96) predicted depression even
      after controlling for incident dementia. CONCLUSION: White matter lesions and
      temporal lobe atrophy preceded 10-year incidence of both dementia and depression
      in 70-year-olds. Shared structural correlates could explain the reported
      associations between dementia and depression. These brain changes may represent
      independent and complementary pathways to dementia and depression. Strategies to
      slow progression of vascular pathology and neurodegeneration could indirectly
      prevent both dementia and depression in older adults.

PMID- 25598325
TI  - Use of two-step grafting to fabricate dual-functional films and site-specific
      functionalized scaffolds.
AB  - Polycaprolactone (PCL) is a widely utilized bioresorbable polymer in tissue
      engineering applications. However, the absence of intrinsic functional groups in
      the polymer backbone necessitates the incorporation of functional chemistries to
      enable the further addition of bioactive molecules to PCL-based surfaces and
      scaffolds. The current study aimed to incorporate two different functional
      groups, amine and carboxylate, first on two-dimensional (2D) spin-coated PCL
      films and, thereafter, throughout all surfaces within three-dimensional (3D)
      porous PCL-based scaffolds, produced using the thermally induced phase separation
      (TIPS) method, but in a spatially separated manner. Specifically, gamma
      irradiation induced grafting of acrylic acid (AA) and 2-aminoethyl methacrylate
      hydrochloride (AEMA) onto PCL was performed in selected solvents and the
      resulting substrates were characterized using X-ray photoelectron spectroscopy
      (XPS), atomic force microscopy (AFM), and contact angle measurements to determine
      the surface free energy. Results demonstrated that stepwise graft
      copolymerization of AEMA and AA allows the fabrication of dual-functional
      surfaces, with chemistry depending on the order of grafting of the two monomers.
      In addition, 3D scaffolds could be decorated exclusively with carboxylate groups
      in the interior, while the outer surface displayed dual-functionality. This
      simple surface modification methodology, with the ability to create spatially
      separated surface functional groups throughout 3D porous scaffolds post their
      fabrication, has the potential to be applied to many current and future scaffold
      systems being investigated in the field of tissue engineering. 

PMID- 25598323
TI  - General and abdominal obesity and risk of esophageal and gastric adenocarcinoma
      in the European Prospective Investigation into Cancer and Nutrition.
AB  - General obesity, as reflected by BMI, is an established risk factor for
      esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia
      adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma
      (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC),
      relates to these cancers remains largely unexplored. Using measured
      anthropometric data from 391,456 individuals from the European Prospective
      Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up,
      we comprehensively assessed the association of anthropometric measures with risk
      of EAC, GCC and GNCC using multivariable proportional hazards regression. One
      hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual
      adjustment, BMI was unrelated to EAC, while WC showed a strong positive
      association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR =
      3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to
      EAC after controlling for WC, while WC remained positively associated (HR = 0.35;
      0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC
      or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more
      strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09
      3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that
      abdominal, rather than general, obesity is an indisputable risk factor for EAC
      and also provides evidence for a protective effect of gluteofemoral
      (subcutaneous) adipose tissue in EAC. Our study further shows that general
      obesity is not a risk factor for GCC and GNCC, while the role of abdominal
      obesity in GCC needs further investigation. 

PMID- 25598331
TI  - Emergence of toxin A-negative, toxin B-positive Clostridium difficile strains:
      epidemiological and clinical considerations.

PMID- 25598332
TI  - The need for a decision: the future of biological science and humanity.

PMID- 25598326
TI  - Anti-type II collagen immune complex-induced granulocyte reactivity is associated
      with joint erosions in RA patients with anti-collagen antibodies.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) patients with autoantibodies against
      collagen type II (CII) are characterized by acute RA onset with elevated
      inflammatory measures and early joint erosions as well as increased production of
      tumor necrosis factor-alpha (TauNuF-alpha) by peripheral blood mononuclear cells
      (PBMC) stimulated by anti-CII immune complexes (IC) in vitro. Polymorphonuclear
      granulocytes (PMN) are abundant in RA synovial fluids, where they might interact
      directly with anti-CII IC in the articular cartilage, but no studies have
      investigated PMN responses towards anti-CII IC. The aim was to investigate
      whether PMN react towards anti-CII IC, and to what extent such reactivity might
      relate to the clinical acute onset RA phenotype associated with elevated levels
      of anti-CII. METHODS: PMN and PBMC isolated from healthy donors were stimulated
      with IC made with a set of 72 baseline patient sera (24 anti-CII positive, 48
      anti-CII negative) chosen from a clinically well-characterized RA cohort with two
      year radiological follow-up with Larsen scoring. PMN expression of cluster of
      differentiation (CD)11b, CD66b, CD16 and CD32 was measured by flow cytometry,
      whereas PMN production of myeloperoxidase (MPO) and interleukin (IL)-17, and PBMC
      production of TauNuF-alpha was measured with enzyme linked immunosorbent assay.
      RESULTS: PMN expression of CD11b, CD66b and MPO, and PBMC production of TauNuF
      alpha were upregulated whereas PMN expression of CD16 and CD32 were downregulated
      by anti-CII IC. CD16, CD66b, and MPO production correlated to serum anti-CII
      levels (Spearman's rho = 0.315, 0.675 and 0.253, respectively). CD16 was
      associated with early joint erosions (P = 0.024, 0.034, 0.046 at baseline, one
      and two years) and CD66b was associated with changes in joint erosions (P = 0.017
      and 0.016, at one and two years compared to baseline, respectively). CD66b was
      associated with baseline C-reactive protein and PBMC production of TauNuF-alpha
      was associated with baseline erythrocyte sedimentation rate, in accordance with
      our earlier findings. No clinical associations were observed for MPO or IL-17.
      CONCLUSION: PMN responses against anti-CII IC are more closely associated with
      early joint erosions than are PBMC cytokine responses. PMN reactivity against
      anti-CII IC may contribute to joint destruction in newly diagnosed RA patients
      with high levels of anti-CII.

PMID- 25598333
TI  - High respiratory virus oropharyngeal carriage rate during Kingella kingae
      osteoarticular infections in children.
AB  - AIM: Kingella kingae osteoarticular (KKO) infections are frequently associated
      with upper respiratory tract infections. However, no comparative studies
      detecting respiratory viruses had ever been performed between KKO and non-KKO
      (NKO). PATIENTS & METHODS: Eighteen viruses were searched by FilmArray((r))
      Respiratory Panel (BioFire Diagnostics, UT, USA) in the oropharynx of 6-to-48
      month-children admitted for KKO and NKO in 2013. RESULTS: At least one virus was
      detected in the oropharynx of 19/21 (90.5%) KKO and 3/8 (37.5%) NKO cases (p =
      0.008). In KKO group, human rhinovirus was predominant (12/21; 57.1%), especially
      during winter (7/11; 63.6%) despite its low concomitant circulation (<10%). Human
      rhinovirus was found in 2/8 (25%) in NKO group. CONCLUSION: Higher prevalence of
      respiratory virus in oropharynx was observed in KKO than NKO, strengthening their
      putative role in KKO pathophysiology.

PMID- 25598334
TI  - Resource-saving advice from an infectious diseases specialist team in a large
      university hospital: an exportable model?
AB  - AIM: To assess epidemiological features of patients for which a consultation by
      the infectious diseases consultation team was required, and the rate of clinical
      advice that led to resource-saving advice (R-SA): discontinuation of
      inappropriate therapy or prophylaxis, de-escalation and switch from parenteral to
      oral therapy. MATERIALS & METHODS: An infectious diseases consultation team was
      implemented in a 1100-bed university hospital in Italy. RESULTS: The most
      frequent infections for which an infectious diseases consultancy was required
      were pneumonia, bloodstream infections (17% by Candida) and urinary tract
      infections. In 828 patients (41.4%), interventions with the possibility of R-SA
      were suggested. CONCLUSION: Resource-saving advices were possible in 41% of
      cases. Recent surgery, having a central venous catheter, bloodstream, abdominal,
      surgical site or bone and joint infections were correlated to a higher
      probability of receiving R-SA.

PMID- 25598335
TI  - Engineering yeast for producing human glycoproteins: where are we now?
AB  - Yeast has advanced as an alternative for mammalian cell culture for the
      production of recombinant therapeutic glycoproteins. Engineered yeast strains not
      only allow to mimic the human N-glycosylation pathway but also specific types of
      human O-glycosylation. This is of great value for therapeutic protein production
      and indispensable to determine the structure-function relationships of glycans on
      recombinant proteins. However, as the technology matures, some limitations have
      come up that may hamper biomedical applications and must be considered to exploit
      the full potential of the unprecedented glycan homogeneity obtained on relevant
      biopharmaceuticals. In this special report, we focus on the recent developments
      in N- and O-glycosylation engineering in yeasts of industrial importance, to
      produce recombinant therapeutics with customized glycans.

PMID- 25598336
TI  - The epidemiology of sexually transmitted infections in the UK: impact of
      behavior, services and interventions.
AB  - Sexually transmitted infections (STIs) are a major public health concern. The UK
      has some of the most advanced STI surveillance systems globally. This article
      uses national surveillance data to describe remarkable changes in STI
      epidemiology in the UK over the last century and explores the behavioral and
      demographic shifts that may explain these trends. The past 10 years have seen
      considerable improvements in STI service provision and the introduction of
      national public health interventions. However, sexual health inequalities persist
      and men who have sex with men, young adults and black ethnic minorities remain a
      priority for interventions. Technological advances in testing and a shift in
      sexual health service commissioning arrangements will present both opportunities
      and challenges in future.

PMID- 25598337
TI  - Noroviruses: epidemiology, immunity and prospects for prevention.
AB  - In recent years, noroviruses have become recognized as an important cause of both
      sporadic and epidemic acute gastroenteritis (AGE), largely due to the improved
      availability of broadly reactive real-time RT-PCR (TaqMan-based RT-PCR) assays.
      While there is substantial diversity among noroviruses, one specific genotype,
      GII.4, is the most common etiology in sporadic and epidemic AGE. Outbreaks of
      norovirus AGE most commonly occur in healthcare facilities and restaurants and
      result in significant morbidity and mortality and substantial healthcare costs.
      Norovirus vaccine development is progressing, and Phase I and II human trials
      have shown proof-of-principle that norovirus vaccines can reduce illness and
      infection.

PMID- 25598338
TI  - Parasitic infections in travelers and immigrants: part I protozoa.
AB  - The growth in international commerce, travel and migration contribute to the
      global emergence of certain parasitic infections. Importation of vectors and food
      products may contribute to the emergence of protozoan infections in nonendemic
      countries. Infections such as malaria are potentially fatal, especially in
      nonimmune patients, and outcome depends largely on timely diagnosis and
      treatment. Diagnosis/management of imported parasitic infections may be complex
      especially as some patients may have underlying immunosuppressive conditions such
      as HIV infection. Major challenges concern the development of improved diagnostic
      techniques, safer/more effective drug therapies and identification of biological
      markers of progression and response to treatment. Imported parasitic diseases
      which may be transmitted vertically or through blood transfusion/organ donation
      could become a public health priority in the near future. Climate change may
      affect arthropod distribution and facilitate the spread of protozoan vector-borne
      diseases. The first part of this review focuses on protozoan infections in
      travelers and immigrants.

PMID- 25598339
TI  - Parasitic infections in travelers and immigrants: part II helminths and
      ectoparasites.
AB  - Travel and migration contribute to the emergence of certain parasites which may
      be imported into nonendemic areas. Noncontrolled importation of food products and
      animals may also contribute to the diagnosis of infections caused by helminths in
      nonendemic countries. Some helminth infections such as strongyloidiasis may be
      life-threatening, especially in immunocompromised patients, and outcome depends
      on correct diagnosis and treatment. Other helminth infections are neglected
      tropical diseases associated with chronic disease and/or disability. Major
      challenges concern the development of improved diagnostic techniques, safer and
      more effective drug therapies and identification of markers of response to
      treatment. The study of these imported infections in travelers and immigrants may
      provide opportunities for research which may not be readily available in resource
      poor endemic countries. Updated reviews and guidelines are necessary as new data
      become available. The second part of this review focuses on infections in
      travelers and immigrants caused by helminths and ectoparasites.

PMID- 25598341
TI  - Leishmania and the macrophage: a multifaceted interaction.
AB  - Leishmania, the causative agent of leishmaniases, is an intracellular parasite of
      macrophages, transmitted to humans via the bite of its sand fly vector. This
      protozoan organism has evolved strategies for efficient uptake into macrophages
      and is able to regulate phagosome maturation in order to make the phagosome more
      hospitable for parasite growth and to avoid destruction. As a result, macrophage
      defenses such as oxidative damage, antigen presentation, immune activation and
      apoptosis are compromised whereas nutrient availability is improved. Many
      Leishmania survival factors are involved in shaping the phagosome and
      reprogramming the macrophage to promote infection. This review details the
      complexity of the host-parasite interactions and summarizes our latest
      understanding of key events that make Leishmania such a successful intracellular
      parasite.

PMID- 25598342
TI  - Gene silencing: a therapeutic approach to combat influenza virus infections.
AB  - Selective gene silencing technologies such as RNA interference (RNAi) and nucleic
      acid enzymes have shown therapeutic potential for treating viral infections.
      Influenza virus is one of the major public health concerns around the world and
      its management is challenging due to a rapid increase in antiviral resistance.
      Influenza vaccine also has its limitations due to the emergence of new strains
      that may escape the immunity developed by the previous year's vaccine. Antiviral
      drugs are the primary mode of prevention and control against a pandemic and there
      is an urgency to develop novel antiviral strategies against influenza virus. In
      this review, we discuss the potential utility of several gene silencing
      mechanisms and their prophylactic and therapeutic potential against the influenza
      virus.

PMID- 25598340
TI  - Protective host immune responses to Salmonella infection.
AB  - Salmonella enterica serovars Typhi and Paratyphi are the causative agents of
      human typhoid fever. Current typhoid vaccines are ineffective and are not widely
      used in endemic areas. Greater understanding of host-pathogen interactions during
      Salmonella infection should facilitate the development of improved vaccines to
      combat typhoid and nontyphoidal Salmonellosis. This review will focus on our
      current understanding of Salmonella pathogenesis and the major host immune
      components that participate in immunity to Salmonella infection. In addition,
      recent findings regarding host immune mechanisms in response to Salmonella
      infection will be also discussed, providing a new perspective on the utility of
      improved tools to study the immune response to Salmonella infections.

PMID- 25598343
TI  - Effect of knocking down the insulin receptor on mouse rod responses.
AB  - Previous experiments have shown that the insulin receptor (IR) is expressed in
      mammalian rods and contributes to the protection of photoreceptors during bright
      light exposure. The role of the insulin receptor in the production of the light
      response is however unknown. We have used suction-electrode recording to examine
      the responses of rods after conditionally knocking down the insulin receptor. Our
      results show that these IR knock-down rods have an accelerated decay of the light
      response and a small decrease in sensitivity by comparison to littermate WT rods.
      Our results indicate that the insulin receptor may have some role in controlling
      the rate of rod response decay, but they exclude a major role of the insulin
      receptor pathway in phototransduction. 

PMID- 25598344
TI  - Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in
      rat models.
AB  - This study investigates the mechanism of the protective effect of Panax
      notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia
      inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3
      (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a
      single dose of cisplatin and a subset of rats were also intraperitoneally
      injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the
      concentrations of urinary N-acetyl-beta-D-glucosaminidase (NAG), blood urea
      nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue
      was examined using H&E-staining, and the mitochondria of renal tubular epithelial
      cells were observed using transmission electron microscopy. The expressions of
      microtubule-associated protein-1 light chain (LC)3, autophagy-related gene
      (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western
      blotting. The expression of HIF-1 was detected by immunohistochemistry. The
      results showed that PNS significantly protected against cisplatin-induced
      nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and
      Scr, the attenuation of renal histopathological changes and the mitochondrial
      damages of renal cells, and the increase of mitochondria autophagosome in renal
      tubular epithelial cells. Additionally, PNS significantly increased the
      expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS
      significantly increased the expression of HIF-1alpha, BNIP3, Atg5 and Beclin-1 in
      rat renal tissue. In conclusion, the protective effect of PNS on cisplatin
      induced nephrotoxicity was mainly due to its ability to enhancing the
      mitochondrial autophagy of renal tissue via the HIF-1alpha/BNIP3 pathway, and
      here is the first demonstration about it.

PMID- 25598346
TI  - Coupling needle-trap devices with comprehensive two-dimensional gas
      chromatography with high-resolution time-of-flight mass spectrometry to rapidly
      reveal the chemical transformation of volatile components from sulfur-fumigated
      ginseng.
AB  - Sulfur-fumigation could alter the quality of white ginseng by damaging the
      bioactive compounds and generating sulfur-containing materials. In the present
      study, coupling needle-trap devices with comprehensive two-dimensional gas
      chromatography and high-resolution time-of-flight mass spectrometry was applied
      to rapidly reveal chemical transformation of volatile components from sulfur
      fumigated ginseng. Thirty-two volatile compounds were not in white ginseng
      samples after sulfur-fumigation. Furthermore, 20 sulfur-containing compounds were
      identified for the first time in volatile oil of sulfur-fumigated white ginseng.
      The established approach could be applied to discriminate sulfur-fumigated white
      ginseng among commercial samples and to control the quality of white ginseng. 

PMID- 25598345
TI  - Does FACS perturb gene expression?
AB  - Fluorescence activated cell sorting is the technique most commonly used to
      separate primary mammary epithelial sub-populations. Many studies incorporate
      this technique before analyzing gene expression within specific cellular
      lineages. However, to our knowledge, no one has examined the effects of
      fluorescence activated cell sorting (FACS) separation on short-term
      transcriptional profiles. In this study, we isolated a heterogeneous mixture of
      cells from the mouse mammary gland. To determine the effects of the isolation and
      separation process on gene expression, we harvested RNA from the cells before
      enzymatic digestion, following enzymatic digestion, and following a mock FACS
      sort where the entire cohort of cells was retained. A strict protocol was
      followed to minimize disruption to the cells, and to ensure that no
      subpopulations were enriched or lost. Microarray analysis demonstrated that FACS
      causes minimal disruptions to gene expression patterns, but prior steps in the
      mammary cell isolation process are followed by upregulation of 18 miRNA's and
      rapid decreases in their predicted target transcripts. (c) 2015 International
      Society for Advancement of Cytometry. 

PMID- 25598347
TI  - Reputation drives cooperative behaviour and network formation in human groups.
AB  - Cooperativeness is a defining feature of human nature. Theoreticians have
      suggested several mechanisms to explain this ubiquitous phenomenon, including
      reciprocity, reputation, and punishment, but the problem is still unsolved. Here
      we show, through experiments conducted with groups of people playing an iterated
      Prisoner's Dilemma on a dynamic network, that it is reputation what really
      fosters cooperation. While this mechanism has already been observed in
      unstructured populations, we find that it acts equally when interactions are
      given by a network that players can reconfigure dynamically. Furthermore, our
      observations reveal that memory also drives the network formation process, and
      cooperators assort more, with longer link lifetimes, the longer the past actions
      record. Our analysis demonstrates, for the first time, that reputation can be
      very well quantified as a weighted mean of the fractions of past cooperative acts
      and the last action performed. This finding has potential applications in
      collaborative systems and e-commerce. 

PMID- 25598349
TI  - Relationship between serum gamma-glutamyltransferase level and leukocyte count in
      Korean children and adolescents.
AB  - BACKGROUND: Elevated gamma-glutamyltransferase (GGT) is an important risk factor
      for cardiometabolic diseases, which may result from chronic low-grade
      inflammation. Leukocyte count is widely considered a marker of inflammation and
      is also an independent predictor of cardiometabolic diseases. This study aimed to
      determine the relationship between GGT and leukocyte count in a representative
      sample of Korean children and adolescents. METHODS: A nationwide cross-sectional
      study was conducted to examine the relationship between GGT and leukocyte count
      in 830 boys and 714 girls (aged 10-18 years), using data from the 2010-2012
      Korean National Health and Nutrition Examination Survey. The odds ratios (ORs)
      and 95% confidence intervals (CIs) for high leukocyte count (>= 75th percentile)
      were calculated across GGT quartiles using multiple logistic regression analyses.
      RESULTS: Leukocyte count gradually increased in accordance with serum GGT
      quartiles in both boys and girls (all p-values < 0.001). The OR (95% CI) for high
      leukocyte of the highest GGT quartile was 2.19 (1.05-4.58) for boys and 2.36
      (1.13-4.93) for girls after adjusting for age, BMI, blood pressure, total
      cholesterol, triglyceride, physical activity, household income, and residential
      area. Similarly, these positive associations were observed in multiple logistic
      regression analysis using log2-transformed serum GGT as a continuous variable.
      CONCLUSIONS: The present study demonstrates a positive relationship between serum
      GGT and leukocyte count. These findings indicate that serum GGT may be closely
      related with subclinical low-grade inflammation in children and adolescents.

PMID- 25598348
TI  - Comparison of fibrin-based clot elasticity parameters measured by free
      oscillation rheometry (ReoRox (r)) versus thromboelastometry (ROTEM (r)).
AB  - BACKGROUND: Whole blood viscoelastic tests such as the fibrin-based
      thromboelastometry (ROTEM((r))) test FIBTEM are increasingly used in the
      perioperative setting to quickly identify deficits in fibrin quality, and to
      guide hemostatic therapy. The recently developed FibScreen2 test of the
      ReoRox((r)) method, based on free oscillation rheometry, also provides an
      evaluation of fibrin clot quality. To date, little information is available on
      the performance of this test in hemodiluted blood, by comparison to FIBTEM.
      METHODS: Whole blood samples from eight healthy volunteers were analyzed using
      FIBTEM and Fibscreen2. Native and diluted (to 33% and 50% using saline, gelatin
      or hydroxyethyl starch [HES]) samples were analyzed. Clot strength parameters,
      including FIBTEM maximum clot firmness (MCF), FIBTEM maximum clot elasticity
      (MCE) and Fibscreen2 maximum elasticity (G'max), were measured. RESULTS: In
      repeatedly measured samples from two volunteers, FIBTEM MCF and Fibscreen2 G'max
      revealed a coefficient of variation (CV) of 5.3 vs. 16.3% and 5.6 vs. 31.7% for
      each volunteer, respectively. Hemodilution decreased clot strength. Both
      Fibscreen2 G'max and FIBTEM parameters decreased proportionally to the dilution
      ratio when saline was used. The observed reductions in FIBTEM and Fibscreen2
      parameters were more severe in samples diluted with gelatin and HES, compared to
      saline. Finally, a regression analysis between FIBTEM MCE and Fibscreen2 G'max
      revealed a poor goodness of fit (r(2) = 0.37, p < 0.0001). CONCLUSIONS:
      ReoRox((r)) Fibscreen2 test has a high coefficient of variation, and its
      application in various hemodilution conditions showed limited comparability with
      the ROTEM((r)) FIBTEM test.

PMID- 25598350
TI  - Comparison of tumor markers and inflammatory biomarkers in chronic obstructive
      pulmonary disease (COPD) exacerbations.
AB  - OBJECTIVE: The aim of the present study was: (a) to measure levels of the tumor
      markers, Carcinoembryonic antigen (CEA), Cancer antigen 19-9 (CA19-9), Cancer
      antigen 125 (CA125), Neuron specific enolase (NSE) and Cytokeratin fragments 19
      (CYFRA21-1); (b) to investigate any correlation between them and the inflammatory
      biomarkers C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR) and
      white blood cells count (WBC), in patients with chronic obstructive pulmonary
      disease (COPD) exacerbation, who belong in groups of severity C and D, as
      classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD);
      (c) and finally, to compare these results in these two groups. MATERIAL AND
      METHODS: Fifty-two patients with COPD exacerbation [35 male/17 female, mean age
      (+/- SD) 68.3 +/- 6.4 years] were the study subjects, and were classified in
      severity groups C (n = 27) and D (n = 25), based on the spirometric
      classification, the number of exacerbations in the preceding year and the
      assessment of their symptoms by GOLD. Results. CEA and CA125 were increased in
      group D. In group C, there was a significant correlation between CRP and CA125 (p
      = 0.05). In group D, there was a significant correlation between WBC and NSE (p =
      0.02), between CRP and CA19-9 (p = 0.02) and NSE (p < 0.001), and between the ESR
      and NSE (p = 0.03). CA125 (p = 0.01) and CA19-9 (p = 0.01) were significantly
      higher in group D compared to group C. In contrast, there was no significant
      difference in two groups for NSE, CEA and CYFRA21-1. CONCLUSION: Certain tumor
      markers were increased and were associated with increased levels of inflammatory
      biomarkers and with the disease severity. Inflammation might have a key
      pathogenetic role linking the above tumor markers with the severity of COPD.

PMID- 25598352
TI  - Role of inflammatory markers as predictors of laparotomy in patients presenting
      with acute abdomen.
AB  - BACKGROUND: There is a need for an ideal indicator of surgery in patients
      presenting with acute abdomen. Several markers have been analysed, but the search
      still continues as none have proven effective. This study aimed to analyse and
      compare the predictive value of plasma procalcitonin (PCT) strip test in patients
      presenting with acute abdomen and identify a useful cut-off value to
      differentiate patients that would benefit with surgery from those that require
      conservative management. METHODS: A prospective study was conducted in the
      department of general surgery from June 2012 to June 2013. Plasma PCT was
      estimated by the semi-quantitative strip test. The levels of plasma PCT and other
      routinely used markers of inflammation were analysed and compared. RESULTS: Of
      the total of 58 patients, 44 patients (76%) were men with a mean age of 45 years.
      Forty patients required emergency surgical intervention. A plasma PCT value of
      >0.5 ng/mL at admission was 80% sensitive and 100% specific for predicting need
      for antibiotics in patients with acute abdomen that were managed conservatively.
      The mean plasma PCT value in the patients undergoing surgery (5.0-10.0 ng/mL) was
      significantly more than in those managed conservatively (0.5-2.0 ng/mL). Using
      receiver operating characteristic (ROC) curves a cut-off for plasma PCT of >5.0
      ng/mL was 75% sensitive and 100% specific for considering surgical intervention
      in patients presenting with acute abdomen. CONCLUSIONS: Plasma PCT (value >5
      ng/mL) could be used as an adjunct to clinical examination to predict requirement
      of surgery in patients presenting with acute abdomen.

PMID- 25598351
TI  - Selective endothelin A receptor antagonism with sitaxentan reduces neointimal
      lesion size in a mouse model of intraluminal injury.
AB  - BACKGROUND AND PURPOSE: Endothelin (ET) receptor antagonism reduces neointimal
      lesion formation in animal models. This investigation addressed the hypothesis
      that the selective ETA receptor antagonist sitaxentan would be more effective
      than mixed ETA / B receptor antagonism at inhibiting neointimal proliferation in
      a mouse model of intraluminal injury. EXPERIMENTAL APPROACH: Antagonism of ETA
      receptors by sitaxentan (1-100 nM) was assessed in femoral arteries isolated from
      adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion
      development was induced by intraluminal injury in mice receiving sitaxentan (ETA
      antagonist; 15 mg.kg(-1) .day(-1) ), A192621 (ETB antagonist; 30 mg.kg(-1) .day(
      1) ), the combination of both antagonists or vehicle. Treatment began 1 week
      before, and continued for 28 days after, surgery. Femoral arteries were then
      harvested for analysis of lesion size and composition. KEY RESULTS: Sitaxentan
      produced a selective, concentration-dependent parallel rightward shift of ET-1
      mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal
      lesion size, whereas ETB and combined ETA / B receptor antagonism did not.
      Macrophage and alpha-smooth muscle actin content were unaltered by ET receptor
      antagonism but sitaxentan reduced the amount of collagen in lesions. CONCLUSIONS
      AND IMPLICATIONS: These results suggest that ETA receptor antagonism would be
      more effective than combined ETA /ETB receptor antagonism at reducing neointimal
      lesion formation.

PMID- 25598353
TI  - C-selective and diastereoselective alkyl addition to beta,gamma-alkynyl-alpha
      imino esters with zinc(II)ate complexes.
AB  - Since umpolung alpha-imino esters contain three electrophilic centers,
      regioselective alkyl addition with traditional organometallic reagents has been a
      serious problem in the practical synthesis of versatile chiral alpha-amino acid
      derivatives. An unusual C-alkyl addition to alpha-imino esters using a Grignard
      reagent (RMgX)-derived zinc(II)ate was developed. Zinc(II)ate complexes consist
      of a Lewis acidic [MgX](+) moiety, a nucleophilic [R3 Zn](-) moiety, and 2 [MgX2
      ]. Therefore, the ionically separated [R3 Zn](-) selectively attacks the imino
      carbon atom ,which is most strongly activated by chelation of [MgX](+) . In
      particular, chiral beta,gamma-alkynyl-alpha-imino esters can strongly promote
      highly regio- and diastereoselective C-alkylation because of structural
      considerations, and the corresponding optically active alpha-quaternary amino
      acid derivatives are obtained within 5 minutes in high to excellent yields.

PMID- 25598355
TI  - The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic
      Immune-Inflammatory and Neuro-Immune Diseases.
AB  - Many patients with systemic immune-inflammatory and neuro-inflammatory disorders,
      including depression, rheumatoid arthritis, systemic lupus erythematosus,
      Sjogren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple
      sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure
      pathological levels of fatigue. The aim of this narrative review is to delineate
      the wide array of pathways that may underpin the incapacitating fatigue occurring
      in systemic and neuro-inflammatory disorders. A wide array of immune,
      inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and
      neurophysiological abnormalities are involved in the etiopathology of these
      disease states and may underpin the incapacitating fatigue that accompanies these
      disorders. This range of abnormalities comprises: increased levels of pro
      inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor
      (TNF) alpha and interferon (IFN) alpha; O&NS-induced muscle fatigue; activation
      of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage
      associated (DAMPs) molecular patterns, including heat shock proteins; altered
      glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and
      O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated
      with altered activities in specific brain regions and muscle pathology, such as
      reductions in maximum voluntary muscle force, downregulation of the mitochondrial
      biogenesis master gene peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites
      within myocytes. As such, both mental and physical fatigue, which frequently
      accompany immune-inflammatory and neuro-inflammatory disorders, are the
      consequence of interactions between multiple systemic and central pathways. 

PMID- 25598356
TI  - Survival benefits of post-acute care for older patients with hip fractures in
      Taiwan: A 5-year prospective cohort study.
AB  - AIM: To evaluate the survival benefits of different models of post-acute care
      (PAC) services for older patients with hip fractures in Taiwan METHODS: This was
      a prospective cohort study that recruited elderly patients with hip fractures
      receiving surgical treatment from 2007 to 2009 for study. All patients were
      provided home-based PAC, institution-based PAC or conventional home care (CHC)
      based on their capacity of family care resources. Functional status and survival
      status was followed for 4 years. RESULTS: Overall, 453 hip fracture patients
      (mean age 81.9 +/- 6.8 years, 58.8% men) were recruited for the present study.
      Among them, 29.4% (133/453) patients received home-based PAC, 25.6% (116/453)
      patients received institution-based PAC and 45.0% (204/453) received CHC. During
      follow up, 28.9% (131/453) died within the mean of 940.3 +/- 453.40 days.
      Adjusted for age, sex, living status, visual acuity, mood status, previous fall
      history, and prefracture activities of daily living (ADL) and instrumental
      activities of daily living (IADL), ADL fully recovered patients were
      significantly more likely to survive in the 4-year follow up (HR 2.791, P = 0.01,
      95% CI 1.261-6.149). Patients receiving either home- or institution-based PAC had
      better survival than the CHC group after adjustment for age, sex, living status,
      visual acuity, mood status, previous fall history, prefracture ADL and IADL (HR
      0.486, P = 0.008, 95% CI 0.284-0.832 for home-based PAC; HR 0.546, P = 0.036, 95%
      CI 0.311-0.960 for institution-based PAC). CONCLUSIONS: PAC services were of
      great survival benefit for elderly hip fracture patients, and the home-based
      model was more likely to achieve complete functional recovery, which was
      important for long-term survival.

PMID- 25598357
TI  - The influence of the connection, length and diameter of an implant on bone
      biomechanics.
AB  - BACKGROUND: Regardless of the multiple options of connections, diameters and
      heights for dental implants, the clinician should know the biomechanical behavior
      of the bone to plan the treatment according to the biological and anatomical
      conditions of each patient, without risk to the long-term treatment success.
      REVIEW: The following review attempts to summarize the relevant literature to
      establish guidelines for clinicians based on the scientific evidence regarding
      the influence by the implant's connection, diameter and length on the bone
      biomechanics. CONCLUSIONS: The length, diameter and connection of each implant
      have a degree of influence in bone biomechanics. Despite the influence of
      different implant connections, diameters and lengths on peri-implant bone stress
      and strain, these characteristics should remain within the physiological limits
      to avoid a pathological overload, bone resorption and consequent risk to the long
      term success of implant-prosthetic treatment.

PMID- 25598358
TI  - Green biotechnology, nanotechnology and bio-fortification: perspectives on novel
      environment-friendly crop improvement strategies.
AB  - Food insecurity and malnutrition are prominent issues for this century. As the
      world's population continues to increase, ensuring that the earth has enough food
      that is nutritious too will be a difficult task. Today one billion people of the
      world are undernourished and more than a third are malnourished. Moreover, the
      looming threat of climate change is exasperating the situation even further. At
      the same time, the total acreage of arable land that could support agricultural
      use is already near its limits, and may even decrease over the next few years due
      to salination and desertification patterns resulting from climate change.
      Clearly, changing the way we think about crop production must take place on
      multiple levels. New varieties of crops must be developed which can produce
      higher crop yields with less water and fewer agricultural inputs. Besides this,
      the crops themselves must have improved nutritional qualities or become
      biofortified in order to reduce the chances of 'hidden hunger' resulting from
      malnourishment. It is difficult to envision the optimum way to increase crop
      production using a single uniform strategy. Instead, a variety of approaches must
      be employed and tailored for any particular agricultural setting. New high-impact
      technologies such as green biotechnology, biofortification, and nanotechnology
      offer opportunities for boosting agricultural productivity and enhancing food
      quality and nutritional value with eco-friendly manner. These agricultural
      technologies currently under development will renovate our world to one that can
      comfortably address the new directions, our planet will take as a result of
      climate change. 

PMID- 25598354
TI  - Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.
AB  - One of the most striking hallmarks shared by various neurodegenerative diseases,
      including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral
      sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates
      that microglial activation in the central nervous system is heterogeneous, which
      can be categorized into two opposite types: M1 phenotype and M2 phenotype.
      Depending on the phenotypes activated, microglia can produce either cytotoxic or
      neuroprotective effects. In this review, we focus on the potential role of M1 and
      M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically
      associated with the neurodegenerative diseases. Generally, M1 microglia
      predominate at the injury site at the end stage of disease, when the
      immunoresolution and repair process of M2 microglia are dampened. This phenotype
      transformation is very complicated in AD due to the phagocytosis of regionally
      distributed beta-amyloid (Abeta) plaque and tangles that are released into the
      extracellular space. The endogenous stimuli including aggregated alpha-synuclein,
      mutated superoxide dismutase, Abeta, and tau oligomers exist in the milieu that
      may persistently activate M1 pro-inflammatory responses and finally lead to
      irreversible neuron loss. The changes of microglial phenotypes depend on the
      disease stages and severity; mastering the stage-specific switching of M1/M2
      phenotypes within appropriate time windows may provide better therapeutic
      benefit. 

PMID- 25598360
TI  - Sonochemical synthesis of gold nanoparticles by using high intensity focused
      ultrasound.
AB  - The sonochemical synthesis of gold nanoparticles (GNPs) with different shapes and
      size distributions by using high-intensity focused ultrasound (HIFU) operating at
      463 kHz is reported. GNP formation proceeds through the reduction of Au(3+) to
      Au(0) by radicals generated by acoustic cavitation. TEM images reveal that GNPs
      show irregular shapes at 30 W, are primarily icosahedral at 50 W and form a
      significant amount of nanorods at 70 W. The size of GNPs decreases with
      increasing acoustic power with a narrower size distribution.
      Sonochemiluminescence images help in the understanding of the effect of HIFU in
      controlling the size and shapes of GNPs. The number of radicals that form and the
      mechanical forces that are generated control the shape and size of the GNPs.
      UV/Vis spectra and TEM images are used to propose a possible mechanism for the
      observed effects. The results presented demonstrate, for the first time, that the
      HIFU system can be used to synthesise size- and shape-controlled metal
      nanoparticles. 

PMID- 25598359
TI  - Impact of a chronic total occlusion in an infarct-related artery on the long-term
      outcome of ventricular tachycardia ablation.
AB  - INTRODUCTION: In patients with a prior myocardial infarction (MI), angiographic
      predictors of ventricular tachycardia (VT) recurrence after ablation are lacking.
      Recently, a proarrhythmic effect of a chronic total occlusion (CTO) in a coronary
      artery has been suggested. METHODS AND RESULTS: A total of 191 patients with
      prior MI were referred to our Hospital between 2010 and June 2013 for a first
      ablation of VT. Of these, 84 patients (44%) with stable coronary artery disease
      that underwent a coronary angiography during the index hospitalization were
      included in this study. A CTO in an infarct-related artery (IRA-CTO) was present
      in 47 patients (56%). Patients with and without IRA-CTO did not differ in terms
      of comorbidities, severity of heart failure, presentation of VT or acute outcome
      of ablation, that was completely successful in 93% of cases. At electroanatomic
      mapping, IRA-CTO was associated with greater scar and especially with greater
      area of border zone (34 cm(2) vs. 19 cm(2) , P = 0.001). Median follow-up was 19
      months (IQR 18). At follow-up, patients with IRA-CTO had a significantly higher
      rate of VT recurrence (47% vs. 16%, P = 0.003). At multivariate analysis, IRA-CTO
      resulted to be an independent predictor of VT recurrence after ablation (HR 4.05,
      P = 0.004). CONCLUSIONS: IRA-CTO is an independent predictor of VT recurrence
      after ablation and identifies a subgroup of patients with high recurrence rate
      despite a successful procedure. IRA-CTO is associated with greater scars and
      border zone area; however, this association does not completely justify its
      proarrhythmic effect.

PMID- 25598362
TI  - The Gellyfish: An in situ equilibrium-based sampler for determining multiple free
      metal ion concentrations in marine ecosystems.
AB  - Free metal ions are usually the most bioavailable and toxic metal species to
      aquatic organisms, but they are difficult to measure because of their extremely
      low concentrations in the marine environment. Many of the current methods for
      determining free metal ions are complicated and time-consuming, and they can only
      measure 1 metal at a time. The authors developed a new version of the
      "Gellyfish," an in situ equilibrium-based sampler, with significantly reduced
      equilibration time and the capability of measuring multiple free metal ions
      simultaneously. By calibrating the Gellyfish to account for its uptake of
      cationic metal complexes and validating them in multi-metal competition
      experiments, the authors were able to determine free metal ion concentrations
      previously collected over 10 mo at 5 locations in Boston Harbor for Cu, Zn, Pb,
      Ni, and Cd. This generated 1 of the largest free metal ion datasets and
      demonstrated the applicability of the Gellyfish as an easy-to-use and inexpensive
      tool for monitoring free ion concentrations of metal mixtures in marine
      ecosystems.

PMID- 25598363
TI  - [Prediction of occult carcinoma in contralateral nodules for unilateral papillary
      thyroid carcinoma].
AB  - OBJECTIVE: To investigate the risks for occult carcinoma in contralateral nodules
      for unilateral papillary thyroid carcinoma. METHODS: The study included 157
      consecutive cases of unilateral papillary thyroid carcinoma with benign nodules
      in the contralateral lobe identified by preoperative ultrasound or fine-needle
      aspiration from January 2011 to December 2013. The patients received total
      thyroidectomies and neck lymph node dissections. The frequency and predictive
      factors for contralateral occult carcinoma in these patients were analyzed.
      RESULTS: A total of 68 patients (43.3%) had occult papillary thyroid carcinoma in
      the contralateral lobe and the maximum diameter of contralateral occult papillary
      carcinoma ranged from 0.1 to 1.2 cm, including <= 0.5 cm in 56 patients, 0.5-1.0
      cm in 9 patients and >1.0 cm in 3 patients respectively. In univariate analysis,
      occult carcinoma in the contralateral lobe was associated with patient age
      (chi(2) = 7.266, P = 0.007) and pathologically multifocality in the ipsilateral
      lobe (chi(2) = 5.090, P = 0.024), but not with family history, tumor size,
      thyroid function, Hashimoto's thyroiditis, perithyroidal invasion, multifocality
      in the ipsilateral lobe, clinically or pathologically node-negative neck. In
      multivariate Logistic an analysis, age (OR = 1.054, P = 0.001) and multifocality
      in the ipsilateral lobe on final pathology (OR = 2.443, P = 0.021) were
      independent predictive factors for contralateral occult papillary thyroid
      carcinoma. CONCLUSIONS: Occult carcinoma is common in the contralateral "benign"
      nodules in patients with unilateral papillary thyroid carcinoma especially in
      young patients or the cases with multifocal tumors.

PMID- 25598361
TI  - Novel mechanisms of controlling the activities of the transcription factors Spo0A
      and ComA by the plasmid-encoded quorum sensing regulators Rap60-Phr60 in Bacillus
      subtilis.
AB  - Bacillus subtilis and its closest relatives have multiple rap-phr quorum sensing
      gene pairs that coordinate a variety of physiological processes with population
      density. Extra-chromosomal rap-phr genes are also present on mobile genetic
      elements, yet relatively little is known about their function. In this work, we
      demonstrate that Rap60-Phr60 from plasmid pTA1060 coordinates a variety of
      biological processes with population density including sporulation, cannibalism,
      biofilm formation and genetic competence. Similar to other Rap proteins that
      control sporulation, Rap60 modulates phosphorylation of the transcription factor
      Spo0A by acting as a phosphatase of Spo0F~P, an intermediate of the sporulation
      phosphorelay system. Additionally, Rap60 plays a noncanonical role in regulating
      the autophosphorylation of the sporulation-specific kinase KinA, a novel activity
      for Rap proteins. In contrast, Rap proteins that modulate genetic competence
      interfere with DNA binding by the transcription factor ComA. Rap60 regulates the
      activity of ComA in a unique manner by forming a Rap60-ComA-DNA ternary complex
      that inhibits transcription of target genes. Taken together, this work provides
      new insight into two novel mechanisms of regulating Spo0A and ComA by Rap60 and
      expands our general understanding of how plasmid-encoded quorum sensing pairs
      regulate important biological processes. 

PMID- 25598364
TI  - [Recurrent laryngeal nerve decompression for bilateral recurrent laryngeal nerve
      paralyses after thyroid surgery].
AB  - OBJECTIVE: To study the feasibility and therapeutic effect of recurrent laryngeal
      nerve (RLN) decompression in the treatment of bilateral paralyzed RLN after
      thyroid surgery. METHODS: From March 2005 to June 2013, 15 cases of bilateral RLN
      paralyses occurring within 3 months after thyroid surgery were treated with RLN
      decompression. Bilateral RLN paralyses were caused by revised thyroid surgery in
      8 cases and by primary thyroid surgery in 7 cases. RESULTS: RLN injuries were
      found in 15 cases/22 side, including RLN-cut in 9 sides and RLN-ligated in 13
      sides. RLN decompression was performed in the 10 cases/13 sides of ligated RLN.
      Vocal cord mobility was detected through electrolaryngoscope for evaluating the
      postoperative functional recovery of decompressed RLN.Of 8 patients with
      bilateral RLN paralyses due to the ligation of RLN after previous revised thyroid
      surgeries, functional adduction and abduction of the vocal cord was recovered
      completely in 4 patients and recovered basically with a slight weak abduction in
      one patient after RLN decompression, and the 5 patients were decannulated in 1-4
      months postoperatively. For 7 patients with bilateral RLN paralyses resulted from
      previous primary surgeries, unilateral or bilateral RLN decompress was performed
      in 2 cases and in 3 cases respectively. The mobility of the paralyzed vocal cord
      restored in 1-6 months after RLN decompression, besides one case with relative
      deficient abduction and one case with slight limited abduction and adduction, and
      the 5 patients were decannulated successfully. CONCLUSION: Exploration surgery
      could be performed as soon as possible in patients with bilateral RLN paralyses
      and RLN decompress is effective for the restoration of the function of the nerve.

PMID- 25598365
TI  - [Preservation of parathyroid during the thyroidectomy].
AB  - OBJECTIVE: To investigate the protection of the parathyroid in the total
      thyroidectomy to avoid the postoperative permanent hypoparathyroidism. METHODS:
      Forty-three consecutive cases underwent total thyroidectomy from June 2013 to
      June 2014 in Nanjing Tongren Hospital were reviewed. Of them 26 cases with
      malignant and 17 cases with benign thyroid diseases. RESULTS: Intraoperatively,
      all 4 parathyroid glands were identified in 27 cases, 3 parathyroids in 10 cases
      and 2 parathyroids in 6 cases. Intraoperative parathyroid transplantation was
      performed in 6 cases, including 5 cases with 1 parathyroid transplantation and 1
      case with 2 parathyroid transplantation. With the follow-up of 1-3 months after
      surgery, 10 cases presented with transient hypocalcemia, 8 cases with temporary
      hypoparathyroidism and no case with permanent hypoparathyroidism. CONCLUSION:
      Accurate identification and conservation in situ or auto-transplantation in total
      thyroidectomy could be effective for prevention of postoperative permanent
      hypoparathyroidism.

PMID- 25598366
TI  - [Evaluation of the efficacy and the limitation of ultrasound-guided core-needle
      biopsy, core-needle aspiration and fine-needle aspiration in micro-nodules of
      thyroid].
AB  - OBJECTIVE: To evaluate the efficacy and the limitation of ultrasound-guided core
      needle biopsy, ultrasound-guided core-needle aspiration and ultrasound-guided
      fine-needle aspiration in micro-nodules of thyroid. METHODS: A retrospective was
      performed in 92 patients with suspectable malignent micro-nodules in thyroid. Of
      them, 52 patients underwent US-CNB and US-FNA and 40 patients underwent US-CNA
      and US-FNA. The diagnoses for the micro-nodules were identified by
      histopathlogical examination after surgery. RESULT: Among 52 cases with both US
      CNB and US-FNA, 41 got nondiagnostic US-CNB and 11 cases successfully got the
      correct diagnoses of US-CNB; 6 cases got the incorrect diagnosis of US-FNA and 46
      cases got the correct diagnosis of US-FNA. Of 40 cases with US-CNA and US-FNA,
      unsatisfactory specimen of US-CNA occurred in 14 cases and satisfactory specimen
      of US-CNA were got in 26 cases; unsatisfactory specimen of US-FNA occurred in 4
      cases and satisfactory specimen of US-FNA. The sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy of US-FNA in 92 cases
      for the diagnosis of malignancy were 93.4%, 86.7%, 97.3%, 72.2% and 92.3%,
      respectively. CONCLUSIONS: US-FNA is the most valuable method for the diagnosis
      of suspectable malignent micro-nodules in thyroid before operation.

PMID- 25598367
TI  - [Effects of aging on air-conducted sound elicited ocular vestibular- evoked
      myogenic potential and cervical vestibular-evoked myogenic potential].
AB  - OBJECTIVE: To identify the aging effects on air-conducted sound (ACS) elicited
      ocular vestibular-evoked myogenic potential (oVEMP) and cervical vestibular
      evoked myogenic potential (cVEMP) in normal Chinese population. METHODS: Nighty
      seven normal subjects (194 ears) were recruited for conventional ACS-oVEMP and
      ACS-cVEMP examinations. The candidates'age were 4-83 years old (Ave. +/- SD, 45.7
      +/- 19.3), 41 male and 56 female, divided into 5 groups according to age. 500 Hz
      short tone burst was employed for examinations. Thresholds were identified and
      the parameters of the responses to 100dB nHL were calculated and compared among
      groups. SPSS 13.0 software was used to analyze the date. RESULTS: As the age
      growing, the response rate for oVEMP decreased. It was recorded 100% in both <=
      10-year-old and 11-30-year-old groups, 84.00% in the 31-50-year-old group, 48.15%
      in the 51-70-year-old group and 15.00% in the > 70-year-old group; while that for
      cVEMP were 100% in both <= 10-year-old group and 11-30-year-old group, 82.00% in
      the 31-50-year-old group, 77.78% in the 51-70-year-old group and 45.00% in the >
      70-year-old group. The thresholds elevated and the amplitudes decreased in both
      examinations with the age growing. However, latencies and latency-intervals of
      both oVEMP and cVEMP examinations displayed minor difference among groups except
      that nI latency of oVEMP prolonged with age growing. CONCLUSIONS: With the age
      growing, the otolithic end organ input pathways degenerate in normal subjects, as
      shown that ACS elicited oVEMP and cVEMP responsed less with higher threshold and
      smaller amplitude. The extremely low response rates of both VEMPs in the > 70
      year-old group in this study indicates that VEMPs can only provide limited
      diagnostic information among very old people in clinical practice.

PMID- 25598368
TI  - [Analysis of the clinical audiological characteristics in 92 Chinese Alport
      syndrome cases].
AB  - OBJECTIVE: To analyze the clinical audiological characteristics in Chinese Alport
      syndrome, and investigate the relationship between the genotypes of Alport
      syndrome and hearing phenotype. METHODS: The clinical hearing data of 92 cases
      diagnosed as Alport syndrome from 2008 August to 2013 August were reviewed and
      analyzed. All coding exons of COL4A3 and COL4A5 genes were PCR-amplified and
      sequenced from genomic DNA, or mRNA of COL4A5 gene was RT-PCR-amplified and
      sequenced from skin fibroblast in 17 cases. RESULTS: Eighty-seven out of 92 cases
      were found with X-linked dominant inheritance (XLAS); 5 cases with autosomal
      recessive (ARAS); 44 cases had normal hearing, but 14 young cases had abnormal
      OAE; 48 cases (52.2%, 35 male, 13 female) had sensorineural hearing loss. A total
      of 44 cases with XLAS had hearing loss (49.4%), wherein the incidence of hearing
      impairment was 55.0% in male XLAS, and 37.0% in female XLAS. Mild and moderate
      hearing loss were found in XLAS. Audiometric curves including groove type (21
      cases), descending type (13 cases), flat type (10 cases), high frequency drop
      type (3 cases) and ascending type (1 case) were found in AS. Sixteen mutations of
      COL4A3, COL4A5 gene were found in 17 cases with Alport syndrome, including severe
      mutation in 8 cases with moderate hearing impairment. CONCLUSIONS: Mild and
      moderate hearing impairment, and groove type of audiometric curve are mainly
      found in Chinese Alport syndrome, which is different from Alport syndrome in
      western countries. OAE in the early diagnosis of hearing loss is important.
      Hearing phenotype is related certainly with genotype.

PMID- 25598370
TI  - [Pediatric airway foreign body misdiagnosed as tracheal stenosis in one case].

PMID- 25598369
TI  - [Function study of non-syndromic deafness associated mitochondrial 12S rRNA A839G
      mutation].
AB  - OBJECTIVE: To investigate the correlation between nonsyndromic deafness and
      mitochondrial 12s rRNA A839G mutation. METHODS: According to the clinical
      manifestations of mitochondrial DNA sequencing and analysis to find and determine
      family containing mitochondrial 12s rRNA A839G mutation. Harvested its family
      members blood and transferred their lymphocytes into lymphoblastoid cell lines,
      followed by cells cultured, cell doubling experiment, susceptibility testing,
      cellular oxygen consumption rate experiment, ROS and mitochondrial membrane
      potential experimental tests were progressed to explore the correlation between
      the A839G mutation and nonsyndromic deafness. RESULTS: The mitochondrial 12s rRNA
      A839G mutation pedigrees were determined through the full sequence detections of
      the Mitochondrial DNA, further phylogenetic analysis showed that 839 point
      conservative index (CI) up to 78.6%; in RPMI-galactose medium containing A839G
      gene mutant cell line, the doubling time was significantly longer than the
      control group, and the difference was significant (P = 0.033). The effect to cell
      lines containing the A839G mutation of aminoglycoside drugs was not obvious. When
      compared with the control group, cell lines containing the A839G mutation
      significantly reduced cellular oxygen consumption rate(P = 0.033); compared with
      the control group, the ROS levels of cell lines containing the A839G mutation
      appeared more substantial elevated with significan difference (P < 0.01). The
      mitochondrial membrane potential of cells of experimental group was significantly
      reduced than the control group. CONCLUSION: The present study proved that the
      mitochondria 12s rRNA A839G mutations affect the function of the mitochondrial
      respiratory chain at the cell level, which might reduce the growth rate of the
      mutant cell lines, result in hearing.

PMID- 25598372
TI  - [Plasma estrogen level and estrogen receptors expression in palatine tonsils in
      male patients with obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To detect the plasma estrogen level and estrogen receptors expression
      in palatine tonsils of male patients with obstructive sleep apnea hypopnea
      syndrom (OSAHS). METHODS: Seventy-six patients with OSAHS were selected as
      experimental group, 45 patients with chronic tonsillitis as the control group.
      The tonsils and adipose tissues in space veli palatin were surgically resected in
      the experimental group, the tonsils were resected in the control group. The
      plasma level of estrogen was evaluated in patients of the two groups with
      chemiluminescence immunoassay respectively. The expression of estrogen receptors
      (ER alpha, ER beta) in palatine tonsils was detected with immunohistochemical
      methods in the two groups. The relationships between the expression of estrogen
      receptors and the patient's age, history of snoring, history of apnea, apnea
      hypopnea index (AHI), body mass index (BMI), neck circumference, abdominal
      circumference, blood pressure, smoking, alcohol drinking, the degree of
      velopharyngeal stenosis, the Epworth sleepiness scale score (ESS), and
      accompanied systemic diseases were analyzed. RESULTS: The estradiol levels did
      not show significant statistical difference between the two groups [(94.94 +/-
      25.54)pmol/L, (104.23 +/- 34.75)pmol/L, respectively]. The estrogen levels in
      OSAHS patients were positively correlated with the patients' AHI (r = 0.76, P <
      0.01), showed positively correlated trends with BMI (r = 0.43, P < 0.01), ESS (r
      = 0.34, P < 0.01), neck circumference (r = 0.31, P = 0.01), abdominal
      circumference (r = 0.32, P < 0.01); the expressions of ER alpha and ER beta in
      the experimental group (36.8%, 48.7%) were lower than that in the control group
      (60.0%, 68.9%) respectively, the difference was statistically significant (chi(2)
      were 5.17 and 4.69, P < 0.05); the expressions of ER alpha and beta in OSAHS
      patients showed negatively correlated trends with the patients' AHI (r = -0.48, P
      < 0.01; r = -0.26, P < 0.05). The expressions of ER alpha in OSAHS patients
      showed positively correlated trends with the patients' lowest oxygen saturation.
      CONCLUSIONS: Estrogen may promote the occurrence of male OSAHS. The ER expression
      in palatine tonsils of male OSAHS patients accorded to the severity of illness,
      may be associated with hypoxia.

PMID- 25598371
TI  - [Multiple-factors analysis on the prognosis of nasal mucosa malignant melanoma].
AB  - OBJECTIVE: To summarize the clinical characteristics and treatment of patients
      with malignant nasal mucosa melanoma, and explore the factors influencing the
      prognosis of malignant nasal mucosa melanoma. METHODS: To retrospectively analyze
      the clinical data of 29 patients with malignant nasal mucosa melanoma in Tianjin
      Huanhu hospital, department of otorhinolaryngology head and neck surgery between
      October, 1999 and June, 2013. Eighteen of them were male, other eleven were
      female, the median age was 61.5 years. The patients were staged according to the
      American Joint Committee on Cancer (AJCC) staging system, eight cases were in T1,
      ten cases were in T2, six cases were in T3, five cases were in T4. Among the 29
      cases, twenty-two patients received surgical treatment, twenty-eight patients
      accepted radiotherapy, seventeen patients had the chemotherapy. The Kaplan-Meier
      method was used to analyze the prognosis impacts of gender, age, disease
      location, clinical staging, treatment, and histopathological features and so on.
      RESULTS: In this series, the overall 3 year survival rate was 48.3% and 5 year
      survival rate was 27.6%. There were 4 factors effecting the 5 year survival rate
      : the location of tumor, T stage, surgical treatment and black pigmentation (P
      value was 0.008, 0.012, 0.021 and 0.027). But, gender, age, chemotherapy and
      other factors had no effect on overall survival rate. CONCLUSIONS: AJCC staging
      system can effectively predict the prognosis of patients. The prognosis of
      patients with pathogenic site in nasal septum is better than the others. The
      surgical treatment is the preferred method of treatment. Histological features
      such as tumor melanin pigmentation affect the prognosis of the patients.

PMID- 25598373
TI  - [Risk factors of acute respiratory dysfunction in children with airway foreign
      body].
AB  - OBJECTIVE: This study aims to analyze the independent risk factors of acute
      respiratory dysfunction (ARD) in children with airway foreign body and to assess
      possible prevention and treatment option in the future. METHODS: Clinical data of
      456 cases of children with airway foreign body were retrospectively collected and
      analyzed by cluster sampling, including 246 males and 210 females, who received
      operation in our hospital between July, 2009 and December, 2012, aged 0.5-11
      years old, onset to treatment time was 0.15-14 days. Clinical characteristics
      including age, gender, past medical history, time of onset, temperature, location
      of the foreign body, category of foreign bodies, complicated by pneumonia,
      complicated by subcutaneous and mediastinal emphysema were gathered. Temperature,
      respiratory rate, heart rate, cyanosis, transcutaneous oxygen saturation or
      arterial blood analysis were assayed before operation. Risk factors with
      statistical significance were screened with univariate logistic regression
      analysis, independent risk factors of ARD were determined with multivariate
      logistic regression analysis. RESULTS: Acute respiratory dysfunction occurred in
      78 (17.1%) patients. The foreign bodies in 455 cases were successfully removed
      brochoscopically in the first time. One case received chest surgery for foreign
      body removal. Total of 452 cases were successfully extubated and ventilator
      weaned 4-6 h after brochoscopy. In 2 cases, the ventilator was weaned 2-4 d after
      brochoscopy in ARD group, and 2 cases with severe pneumonia died. Age, location
      of the foreign body, temperature, complicated by pneumonia, complicated by
      subcutaneous and mediastinal emphysema did not show significant difference
      between acute respiratory dysfunction group and non- acute respiratory
      dysfunction group (P < 0.05). Multivariate logistic regression analysis showed
      location of the foreign body and complicated by pneumonia, complicated by
      subcutaneous and mediastinal emphysema were independent risk factors for ARD.
      CONCLUSION: Early judgement of the risk factors of acute respiratory dysfunction
      in children with airway foreign body can provide a reference for the operation
      and perioperation period treatment.

PMID- 25598374
TI  - [The spiral ganglion degeneration and the expression of EFR3A in the cochlea of
      the deaf mice induced by co-administration of kanamycin and furosemide].
AB  - OBJECTIVE: To investigate the spiral ganglion degeneration and the expression of
      EFR3A in the cochlea of the deaf mice induced by co-administration of kanamycin
      and furosemide. METHODS: Eight weeks old C57BL/6J mice were administered with a
      single dose of kanamycin followed by furosemide, then fluorescent
      immunohistochemistry staining and transmission electron microscopy were applied
      to observe the SGNs' degeneration process and extent characteristics at 1, 5, 15,
      30 and 60 days following treatment. We detected the expression of EFR3A during
      the degeneration of SGNs via fluorescent immunohistochemistry and western
      blotting. RESULTS: Co-administration of kanamycin and furosemide quickly induced
      cochlear hair cell death in mice, and then caused progressive degeneration of
      SGNs. Our results showed that the abnormal morphology of SGNs occurredat day 5
      following administration, and the number of SGNs began to decrease at day 15.
      Compared to the control group, it was found the remarkable increase of the EFR3A
      protein at the fifth day after co-administration, then decreased to the nearly
      normal at 15 days following treatment, and no further significant changes
      thereafter. CONCLUSION: The changes of the EFR3A protein expression in the spiral
      ganglion of the cochlea in mice are coincidence with the time of the SGNs
      degeneration to happen, which imply that EFR3A may play an important role in the
      occurrence of the SGNs' degeneration in the cochlea in mice following hair cells
      loss.

PMID- 25598375
TI  - [Experimental study on the impact of photodynamic therapy on the tissue structure
      of normal nasal mucosa in rabbit].
AB  - OBJECTIVE: To study the reactive changes of normal nasal mucosa in rabbit under
      photodynamic therapy (PDT) and to make a preliminary research for the treatment
      of allergic rhinitis (AR) with PDT. METHODS: Twenty-four New Zealand rabbits were
      divided into 2 groups, an experimental group and a control group with 12 rabbits
      in each group. PDT was applied to the experimental group, while the control group
      was given no treatment. The nasal mucosa was sampled separately from the same
      position of the rabbits from the 2 groups on 1st, 3rd, 7th, 14th, 21st, 28th day.
      Histomorphological changes of the sampled nasal mucosa were observed under light
      microscope and transmission electron microscope (TEM). The damage of three
      tachykinins: substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) of nerve
      fibers was observed after immunohistochemical staining. RESULTS: Compared with
      the control group, the nasal mucosa tissues from the experimental group had
      serious inflammatory reaction with basal layer damaged on the 1st and 3rd day
      after PDT application, the epithelial cells of nasal mucosa were arranged in
      disorder, and part of cilium shortened and became abnormal or even disappeared,
      each organelles damaged obviously; on the 7th, 14th, 21st day, it could be seen
      that ciliated cell, columnar cell and goblet cell started regeneration, basal
      cell and lamina propria glands proliferated, and the glands appeared secretion
      phenomenon; on the 28th day, ciliated columnar epithelium took back the nasal
      mucosas with small amount of microvilli, and mucous granules were found in the
      column cells. Nasal immunohistochemical staining of the experimental group from
      various stages showed that three kinds of neuropeptides were not expressed.
      CONCLUSIONS: Normal rabbit nasal mucosas will be temporarily damaged after PDT
      application, the damaged nasal mucosa begin to recover in one week, and return to
      normal in about four weeks. Most structure and functions have recovered at the
      fourth week except some nerve endings.

PMID- 25598376
TI  - [Inhibitory effect of full-length spleen tyrosine kinase on invasion and
      metastasis of human laryngeal squamous cells].
AB  - OBJECTIVE: To study the effect of gene transfection of full length spleen
      tyrosine kinase (Syk (L)) on the biological behavior of malignant cancer cells.
      METHODS: Eukaryotic expression vector pIRES2-EGFP-Syk (L) was constrauted and
      sequenc. Laryngeal carcinoma cell line Hep-2 were transfected with pIRES2-EGFP
      Syk (L) vectors or blank vectors. The expressions of mRNA and protein were
      examined by real time fluorescence quantitative polymerase chain reaction (Q-RT
      PCR) and Western blot analysis. CCK-8 method was used for evaluating cell
      proliferation, Transwell for cell invasion capacity in vitro, and tumor formation
      in nude mice for in vivo tumorigenicity. RESULTS: pIRES2-EGFP-Syk (L) vectors
      were successfully construct and transfected to Hep-2 cells. Q-PCR showed that
      mRNA expression level in Hep-2 cells transfected with Sky (L) (28.395 +/- 0.067)
      was higher than those in Hep-2-neo cells transfected with blank vectors (3.891 +/
      0.021) and Hep-2 cells with no transfection (1.005 +/- 0.012), with
      statistically significant difference (F = 104.02, P < 0.01). Western blot showed
      that protein expression level of transfected-Sky (L) cells (0.821 +/- 0.047) was
      significantly higher than those of Hep-2-neo cells (0.558 +/- 0.031) and Hep-2
      cells (0.468 +/- 0.031), and the difference was statistically significant (F =
      112.32, P < 0.01) ; CCK-8 assay showed OD value (1.390 +/- 0.067) of transfected
      Sky (L) cells was lower than those of Hep-2-neo cells (1.830 +/- 0.067) and Hep-2
      cells (1.920 +/- 0.040), and the difference was statistically significant (F =
      107.64, P < 0.01). Transwell assay showed average cell number per field of
      transfected-Sky (L) cells (176.04 +/- 22.32) was higher than those of Hep-2-neo
      cells (301.02 +/- 21.45) and Hep-2 cells (336.04 +/- 26.01) with statistically
      significant difference (F = 123.46, P < 0.01). The volume (250.77 +/- 34.83)
      mm(3) tumor formed from transfected-Sky (L) cells in nude mice, was less than
      those from Hep-2-neo cells (750.77 +/- 40.83) mm(3) and Hep-2 cells (770.77 +/-
      30.83) mm(3), with statistically significant difference (F = 165.78, P < 0.01).
      CONCLUSION: Down-regulation of Syk in Hep-2 cells is associated with the
      malignant biological behaviors of the cells. Syk (L) may be a potential target in
      gene therapy for laryngeal squamous cell carcinoma.

PMID- 25598377
TI  - [Investigation of chronic rhinosinusitis on junior middle school students in
      Zhengzhou area in 2009].
AB  - OBJECTIVE: To investigate the incidence of chronic rhinosinusitis and its
      influence on life quality for junior middle school students in Zhengzhou
      Municipal. METHODS: Two thousand and twenty junior middle school students in
      Zhengzhou Municipal were randomly selected as the object of investigation by
      designed survey and visual analogue scale (VAS) questionnaire of chronic
      rhinosinusitis the sino-nasal outcome test-20 (SNOT-20) and nasal examination.
      Effect on the quality of life was investigated based on the degree of troubles
      caused by symptoms. RESULTS: The incidence of chronic rhinosinusitis in junior
      middle school students in Zhengzhou Municipal was 6.73% (136/2 020), in which,
      22.79% (31/136) of these students' quality of life was affected (VAS>5).
      CONCLUSIONS: Chronic rhinosinusitis is common in junior middle school students,
      and the life quality is affected. So we should pay attention to this diseases and
      take the positive and effective intervention measures.

PMID- 25598378
TI  - [The clinical features and prognosis of radiotherapy associated sarcoma (RAS)
      following radiotherapy for nasopharyngeal carcinoma].
AB  - OBJECTIVE: To analyze the clinical features and prognosis of radiotherapy
      associated sarcoma (RAS) in the head and neck following radiotherapy for
      nasopharyngeal carcinoma (NPC). METHODS: The clinicopathologic data, diagnosis,
      treatment and follow-up results of 11 patients with RAS diagnosed between January
      1995 and December 2011 at Zhejiang Cancer Hospital were analyzed retrospectively.
      Among these patients, 6 were males and 5 were females. Patients' ages ranged from
      33 to 66 years (median 50 years). The latency period for development of the RAS
      was between 3 years and 23 years (median 7 years) after irradiation. Overall
      survival rate was calculated using the Kaplan-Meier method and Log rank test.
      RESULTS: All cases underwent surgery, of them 6 casesachieved radical resection3
      cases left with microscopic positive resection margins and 2 caseshad palliative
      surgery. Among 11 patients, 4 had re-surgery after recurrence, including 1 case
      had repeated surgeries followed by chemotherapy and radioactive seed
      implantation. Follow-up time ranged from 2 to 102 months, andeight patients died
      The 2-year, 3-year and 5-year cumulative survival rateswere 45.5%, 30.3% and
      15.2%, respectively. The median survival time was 15 months. Surgical resection
      with clear margins achieved significantly better prognosis (P = 0.04).
      CONCLUSIONS: The incidence of RAS after radiation of NPC is generally low, but
      the treatment of RAS is very difficult, with poor prognosis.

PMID- 25598380
TI  - [Foreign body in neck for 40 years with nodular goiter: 1 case report].

PMID- 25598379
TI  - [One case of nasal cellular schwannoma].

PMID- 25598381
TI  - [Estrogen and its receptor: another promoter in the occurrence and evolution of
      differentiated thyroid carcinoma].

PMID- 25598382
TI  - [Efficacy of surgery, recurrence factors and treatment strategies of otitis media
      with effusion in children].

PMID- 25598383
TI  - [Summary of International Federation of Head and Neck Oncologic Societies 5th
      world congress, American Head & Neck Society annual meeting].

PMID- 25598385
TI  - Involvement of seminal leukocytes, reactive oxygen species, and sperm
      mitochondrial membrane potential in the DNA damage of the human spermatozoa.
AB  - Measurement of reactive oxygen species (ROS) producing leukocytes in semen has
      been a standard component of the semen analysis, but its true significance
      remains still unknown. In this study, we have correlated the number of seminal
      leukocytes to various semen parameters. We found a negative correlation between
      the leukocyte number and sperm concentration (rs  = -0.22; p = 0.01) and motility
      (rs  = -0.20; p = 0.02). In contrast, a positive correlation between the number
      of leukocytes and both seminal ROS (rs  = 0.70, p < 0.001; n = 125) and the
      number of spermatozoa with DNA fragmentation (rs  = 0.43, p = 0.032; n = 25) was
      found. However, only a trend of positive correlation between ROS and the number
      of spermatozoa with TUNEL-detected DNA fragmentation was observed. Moreover, this
      latter was not correlated with loss of sperm mitochondrial membrane potential
      (MMP) (10% vs 35%, rs  = 0.25, p = 0.08; n = 50). Overall these results indicate
      that the presence of high number of leukocytes in the ejaculate negatively
      affects key semen parameters, as sperm concentration and motility, associated
      with infertility conditions. Moreover, they suggest that leukocytes are the major
      source of the seminal ROS and cause of sperm DNA fragmentation. However, the
      absence of a clear correlation between ROS and sperm DNA fragmentation, and
      spermatozoa with damaged DNA and MMP loss, suggest that ROS produced by
      leukocytes might be not the only cause of DNA damage in spermatozoa and that
      intrinsic mitochondrial-dependent apoptotic pathways might not have a major
      impact on sperm DNA fragmentation. 

PMID- 25598386
TI  - Improved photoactivity of TiO2-Fe2O3 nanocomposites for visible-light water
      splitting after phosphate bridging and its mechanism.
AB  - In this work, we have successfully constructed phosphate bridges in a TiO2-Fe2O3
      nanocomposite using wet-chemical processes. Based on FTIR, XPS and TEM
      measurements it is confirmed that phosphate groups form bridges that effectively
      connect TiO2 and alpha-Fe2O3. From steady-state surface photovoltage spectra (SS
      SPS) and transient-state surface photovoltage (TS-SPV) measurements in N2, it is
      clearly demonstrated that the separation and lifetime of the photogenerated
      charge carriers in the TiO2-Fe2O3 nanocomposite are greatly enhanced by the
      introduction of the phosphate bridges. As a consequence, the visible light
      photocatalytic activity in water reduction by methanol and the
      photoelectrochemical water oxidation were obviously improved after phosphate
      bridging. It is concluded mainly on the basis of ultra-low-temperature EPR
      signals, EIS spectra, and the normalized photocurrent action spectra that the
      photogenerated electrons of alpha-Fe2O3 under irradiation with visible light
      would transfer to TiO2 in the nanocomposite, and the built phosphate bridges are
      favorable for charge transportation, leading to the greatly-increased separation
      and lifetime of visible-light excited charge carriers. This work provides a
      feasible route to improve the photoactivity of other visible-response
      nanocomposites for water splitting. 

PMID- 25598384
TI  - Control Outcomes and Exposures for Improving Internal Validity of Nonrandomized
      Studies.
AB  - OBJECTIVE: Control outcomes and exposures can improve internal validity of
      nonrandomized studies by assessing residual bias in effect estimates. Control
      outcomes are those expected to have no treatment effect or the opposite effect of
      the primary outcome. Control exposures are treatments expected to have no effect
      on the primary outcome. We review examples of control outcomes and exposures from
      prior studies and provide recommendations for conducting and reporting these
      analyses. DATA SOURCES AND STUDY DESIGN: Review in Google Scholar and Medline of
      research studies employing control outcomes or exposures. We abstracted
      publication year, control outcome, control exposure, primary outcome, primary
      exposure, control outcome/exposure effect, proposed source of bias, and causal
      criteria. PRINCIPAL FINDINGS: There is inconsistent terminology for these
      concepts, making study identification challenging. Six of 11 studies found null
      associations between treatments and negative control outcomes/exposures,
      providing greater confidence that the primary study findings were not biased.
      Five studies found unexpected associations, suggesting bias in the primary
      association. CONCLUSIONS: The rigor of nonrandomized studies can be improved with
      inclusion of control outcomes and exposures for bias detection. Given ongoing
      concern about clinical and policy inferences from nonrandomized studies, we
      recommend adoption of these measurement tools.

PMID- 25598387
TI  - Precursor polymers for the carbon coating of Au@ZnO multipods for application as
      active material in lithium-ion batteries.
AB  - The synthesis of statistical and block copolymers based on polyacrylonitrile, as
      a source for carbonaceous materials, and thiol-containing repeating units as
      inorganic nanoparticle anchoring groups is reported. These polymers are used to
      coat Au@ZnO multipod heteroparticles with polymer brushes. IR spectroscopy and
      transmission electron microscopy prove the successful binding of the polymer onto
      the inorganic nanostructures. Thermogravimetric analysis is applied to compare
      the binding ability of the block and statistical copolymers. Subsequently, the
      polymer coating is transformed into a carbonaceous (partially graphitic) coating
      by pyrolysis. The obtained carbon coating is characterized by Raman spectroscopy
      and energy-dispersive X-ray (EDX) spectroscopy. The benefit of the conformal
      carbon coating of the Au@ZnO multipods regarding its application as lithium-ion
      anode material is revealed by performing galvanostatic cycling, showing a highly
      enhanced and stabilized electrochemical performance of the carbon-coated
      particles (still 831 mAh g(-1) after 150 cycles) with respect to the uncoated
      ones (only 353 mAh g(-1) after 10 cycles).

PMID- 25598388
TI  - The role of romantic attachment security and dating identity exploration in
      understanding adolescents' sexual attitudes and cumulative sexual risk-taking.
AB  - This study addressed how two normative developmental factors, attachment and
      identity, are associated with adolescents' sexual attitudes and sexual risk
      taking behavior. The sample consisted of 2029 adolescents (mean age = 16.2 years)
      living in the Southeast United States. Path analysis was used to test the
      hypotheses. Higher levels of attachment anxiety predicted more dating identity
      exploration and less healthy sexual attitudes. Higher levels of attachment
      avoidance predicted less dating identity exploration and indirectly predicted
      less healthy sexual attitudes through dating identity exploration. Females with
      dating or sexual experience showed the weakest associations between the
      attachment dimensions and dating identity exploration. More dating identity
      exploration predicted healthier sexual attitudes; this association was strongest
      for non-virgins. Finally, higher levels of attachment avoidance were associated
      with higher cumulative sexual risk scores, but only among non-virgin males.
      Results are interpreted in light of theory and research on attachment, identity
      exploration, and adolescent sexual relationships.

PMID- 25598389
TI  - Paediatric ventilation tube insertion: our experience of seventy-five children in
      audiology-led follow-up.

PMID- 25598391
TI  - Nurse-physician collaboration and associations with perceived autonomy in Cypriot
      critical care nurses.
AB  - BACKGROUND AND AIMS: Increased nurse-physician collaboration is a factor in
      improved patient outcomes. Limited autonomy of nurses has been proposed as a
      barrier to collaboration. This study aims to explore nurse-physician
      collaboration and potential associations with nurses' autonomy and pertinent
      nurses' characteristics in adult intensive care units (ICUs) in Cyprus. DESIGN
      AND METHODS: Descriptive correlational study with sampling of the entire adult
      ICU nurses' population in Cyprus (five ICUs in four public hospitals, n = 163,
      response rate 88.58%). Nurse-physician collaboration was assessed by the
      Collaboration and Satisfaction About Care Decisions Scale (CSACD), and autonomy
      by the Varjus et al. scale. RESULTS: The average CSACD score was 36.36 +/- 13.30
      (range: 7-70), implying low levels of collaboration and satisfaction with care
      decisions. Male participants reported significantly lower CSACD scores (t =
      2.056, p = 0.04). CSACD correlated positively with years of ICU nursing
      experience (r = 0.332, p < 0.0001) and professional satisfaction (r = 0.455, p <
      0.0001). The mean autonomy score was 76.15 +/- 16.84 (range: 18-108). Higher
      degree of perceived collaboration (CSACD scores) associated with higher autonomy
      scores (r = 0.508, p <0.0001). CONCLUSIONS: Our findings imply low levels of
      nurse-physician collaboration and satisfaction with care decisions and moderate
      levels of autonomy in ICU nurses in Cyprus. RELEVANCE TO CLINICAL PRACTICE: The
      results provide insight into the association between nurse-physician
      collaboration and nurses' autonomy and the correlating factors.

PMID- 25598392
TI  - Letter to the Editor regarding article on exercise-induced pulmonary haemorrhage
      at the Hong Kong Jockey Club.

PMID- 25598390
TI  - The role of the lymphatic system in inflammatory-erosive arthritis.
AB  - Rheumatoid arthritis (RA) is a prevalent inflammatory joint disease with
      enigmatic flares, which causes swelling, pain, and irreversible connective tissue
      damage. Recently, it has been demonstrated in murine models of RA that the
      popliteal lymph node (PLN) is a biomarker of arthritic flare, as it "expands" in
      size and contrast enhancement during a prolonged asymptomatic phase, prior to
      when it "collapses" with accelerated synovitis and joint erosion. This PLN
      collapse is associated with adjacent knee flare, decreases in PLN volume and
      contrast enhancement, lymphatic pulse and pumping pressure, and an increase in
      PLN pressure. Currently, it is known that PLN collapse is accompanied by a
      translocation of B cells from the follicles to the sinuses, effectively clogging
      the lymphatic sinuses of the PLN, and that B cell depletion therapy ameliorates
      arthritic flare by eliminating these B cells and restoring passive lymphatic flow
      from inflamed joints. Here we review the technological advances that have
      launched this area of research, describe future directions to help elucidate the
      potential mechanism of PLN collapse, and speculate on clinical translation
      towards new diagnostics and therapies for RA. 

PMID- 25598393
TI  - Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent memory
      impairment in Fischer 344 rats.
AB  - To understand the anti-inflammaging effect of lactic acid bacteria, we selected
      NF-kappaB activation-inhibitory Lactobacillus pentosus var. plantarum C29 and
      investigated its memory-enhancing and anti-inflammatory effects in aged Fischer
      344 rats. C29 (2 * 10(9) CFU rat(-1) ), which was orally administered once a day
      (6 days per week) for 8 weeks, significantly restored age-reduced spontaneous
      alternation to 95.2% of that seen in young rats (P < 0.05). C29 treatment also
      shortened the escape latency on the 4th day to 53.8% of that seen in young rats
      (P < 0.05). Twenty hours after the last training session, C29 significantly
      increased the swimming time within the platform quadrant, which was shortened in
      the aged control rats. Oral administration of C29 restored age-reduced
      doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) expression and
      cAMP response element binding protein (CREB) activation in aged rats. Treatment
      of aged rats with C29 suppressed the expression of p16, cyclooxygenase-2, and
      inducible nitric oxide synthase, as well as the activation of Akt, mTOR, and NF
      kappaB in the hippocampus. These findings suggest that C29 ameliorates ageing
      dependent memory impairment by inhibiting NF-kappaB signalling pathway, inducing
      DCX and BDNF expression and activating CREB. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The anti-inflammatory Lactobacillus pentosus var. plantarum C29 had the
      memory-enhancing effect in aged Fischer 344 rats by restoring doublecortin and
      brain-derived neurotrophic factor expression and suppressing p16 expression and
      NF-kappaB activation in the brain. Therefore, C29 may be useful in ameliorating
      age-related degenerative dementia.

PMID- 25598394
TI  - Allogeneic stem cell transplantation for refractory acute myeloid leukemia: a
      single center analysis of long-term outcome.
AB  - For patients with refractory acute myeloid leukemia (AML), allogeneic stem cell
      transplantation (alloSCT) represents the only curative approach. We here analyzed
      the long-term outcome of 131 consecutive patients with active AML, which was
      either primary refractory or unresponsive to salvage chemotherapy, transplanted
      at our center between 1997 and 2013. After a median follow-up of 48 months for
      the surviving patients, disease-free survival (DFS) at 5 yr post alloSCT was 26%
      (94% CI: 17-35). Relapses, most of which occurred within the first 2 yr from
      transplant, were the predominant cause of treatment failure affecting 48% (95%CI:
      40-58) of patients, whereas non-relapse mortality was 26% (95%CI: 20-36) at 5 yr
      and thereafter. A marrow blast count >=20% before alloSCT was an independent
      prognosticator associated with an inferior DFS (HR: 1.58, P = 0.027), whereas the
      development of chronic graft-versus-host disease (cGvHD) predicted an improved
      DFS (HR 0.21, P < 0.001) and a decreased relapse incidence (HR: 0.18, P = 0.026),
      respectively. These results indicate that alloSCT represents a curative treatment
      option in a substantial proportion of patients with refractory AML. A
      pretransplant blast count <20% before alloSCT and the development of cGvHD are
      the most important predictors of long-term disease control. 

PMID- 25598395
TI  - Age of dementia diagnosis in community dwelling bilingual and monolingual
      Hispanic Americans.
AB  - Bilingualism has been reported to delay the age of retrospective report of first
      symptom in dementia. This study determined if the age of clinically diagnosed
      Alzheimer's disease and vascular dementia occurred later for bilingual than
      monolingual, immigrant and U.S. born, Hispanic Americans. It involved a secondary
      analysis of the subset of 81 bi/monolingual dementia cases identified at yearly
      follow-up (1998 through 2008) using neuropsychological test results and objective
      diagnostic criteria from the Sacramento Area Latino Study on Aging that involved
      a random sampling of community dwelling Hispanic Americans (N = 1789). Age of
      dementia diagnosis was analyzed in a 2 * 2 (bi/monolingualism * immigrant/U.S.
      born) ANOVA that space revealed both main effects and the interaction were non
      significant. Mean age of dementia diagnosis was descriptively (but not
      significantly) higher in the monolingual (M = 81.10 years) than the bilingual (M
      = 79.31) group. Overall, bilingual dementia cases were significantly better
      educated than monolinguals, but U.S. born bilinguals and monolinguals did not
      differ significantly in education. Delays in dementia symptomatology pertaining
      to bilingualism are less likely to be found in studies: (a) that use age of
      clinical diagnosis vs. retrospective report of first dementia symptom as the
      dependent variable; and (b) involve clinical cases derived from community samples
      rather than referrals to specialist memory clinics. 

PMID- 25598396
TI  - An Acute Multispecies Episode of Sheep-Associated Malignant Catarrhal Fever in
      Captive Wild Animals in an Italian Zoo.
AB  - In July 2011, in a zoological garden in Rome, Italy, malignant catarrhal fever
      (MCF), a fatal, systemic disease of Artiodactyla, was suspected on the basis of
      neurological signs and gross lesions observed in a banteng, the first animal to
      die of this infection. An MCF type-specific PCR with subsequent sequencing of the
      PCR amplicon confirmed the aetiological agent as ovine herpesvirus-2 (OvHV-2).
      Biological samples were collected from the dead animals for gross, histological,
      bacteriological, virological and serological examinations. An epidemiological
      investigation was conducted to identify the source of the outbreak, as further
      deaths due to OvHV-2 still occurred after the removal of the acknowledged
      reservoirs, domestic sheep and goats. For this purpose, samples from other
      susceptible species and reservoir hosts were collected for virological and
      serological analysis. In conjunction, a retrospective sero-investigation was
      conducted on sera collected between 1999 and 2010 from some of the species
      involved in the present episode. In total, 11 animals belonging to four different
      species (banteng, Himalayan tahr, Nile lechwe and sika deer) died between July
      2011 and October 2012. The severe gross and histological lesions were consistent
      with the disease, namely haemorrhages and congestion of several organs as well as
      lymphoid cell infiltrates and vasculitis of varying severity. The virological
      tests confirmed that all animals had died of sheep-associated MCF. The
      investigation indicated that the OvHV-2 infection could have been due to the
      arrival of sheep in the petting zoo, with cases commencing after first lambing
      and subsequent shedding of virus. This was also supported by the serological
      retrospective study that indicated limited previous MCF virus circulation.
      Further MCF cases that occurred even after the removal of the domestic sheep and
      goats were attributed to the mouflon. This episode confirms the importance of
      biosecurity measures in zoos, which house MCF susceptible species, especially
      those endangered.

PMID- 25598398
TI  - Assessment of standing balance in patients after ankle fractures.
AB  - PURPOSE: The objective of the study is to evaluate the degree of balance
      disorders in patients with surgical treatment of ankle fractures with the use of
      stabilometric examinations. METHODS: The subjects in the study were 21 patients
      with ankle fractures treated surgically, within one year of the procedure. The
      control group comprised 20 healthy subjects. The balance was evaluated with the
      use of force platform in standing posture in both single and double limb stance.
      The parameters analysed were the transition area of the centre of feet pressure
      (COP), the length of the COP path and the COP velocity. The range of movement in
      the ankle joint and the intensification of pain were also measured. RESULTS: In
      the balance evaluation in double limb stance, there were no statistically
      significant differences. A significant difference was found in the attempts of
      single limb-stance. An average value of COP transition area in the study group
      was 261.2 mm2 in single stance (on the right operated limb) and in the control
      group--93.2 mm2, so the difference was statistically significant (p = 0.0096).
      The presence of pain, the presence or the removal of anastomosis had no
      significant influence on the balance of the subjects under study. Also a
      significant correlation between the balance of the subjects and their age was
      found. CONCLUSIONS: The balance in single limb stance after an instable ankle
      fracture within one year of the surgical procedure is significantly poorer in
      comparison with healthy subjects. Elderly persons have significantly poorer
      balance control.

PMID- 25598397
TI  - Reduced neural connectivity but increased task-related activity during working
      memory in de novo Parkinson patients.
AB  - OBJECTIVE: Patients with Parkinson's disease (PD) often suffer from impairments
      in executive functions, such as working memory deficits. It is widely held that
      dopamine depletion in the striatum contributes to these impairments through
      decreased activity and connectivity between task-related brain networks. We
      investigated this hypothesis by studying task-related network activity and
      connectivity within a sample of de novo patients with PD, versus healthy
      controls, during a visuospatial working memory task. METHODS: Sixteen de novo PD
      patients and 35 matched healthy controls performed a visuospatial n-back task
      while we measured their behavioral performance and neural activity using
      functional magnetic resonance imaging. We constructed regions-of-interest in the
      bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal
      cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in
      task-related activity. We studied network connectivity by assessing the
      functional connectivity of the bilateral DLPFC and by assessing effective
      connectivity within the frontoparietal and the frontostriatal networks. RESULTS:
      PD patients, compared with controls, showed trend-significantly decreased task
      accuracy, significantly increased task-related activity in the left DLPFC and a
      trend-significant increase in activity of the right DLPFC, left caudate nucleus,
      and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC
      with other task-related regions, such as the inferior and superior frontal gyri,
      in the PD group, and group differences in effective connectivity within the
      frontoparietal network. INTERPRETATION: These findings suggest that the increase
      in working memory-related brain activity in PD patients is compensatory to
      maintain behavioral performance in the presence of network deficits.

PMID- 25598400
TI  - Huge infra renal abdominal aortic aneurysm presented with concomitant
      divirticular abscess: A case report.
AB  - INTRODUCTION: It is a controversial and difficult problem for a surgeon to manage
      the simultaneously occurring diseases divirticular abscess and abdominal aortic
      aneurysm. Mostly surgeons are not willing to execute a non vascular procedures
      during the repair of an aneurysm because there can be a risk of graft infection.
      PRESENTATION OF CASE: In this case study, we have explained about the
      presentation of a huge infrarenal abdominal aortic aneurysm (AAA) that is found
      to be associated with a divirticular abscess and both needed an intervention.
      DISCUSSION: It has been suggested by various evidences that a one-stage elective
      surgical treatment is safer and cost effective for the treatment of patients with
      an abdominal aortic aneurysm associated with other problems like gastro
      intestinal malignancies. However, the high risk of graft infection made the two
      staged procedure a popular option. CONCLUSION: The major dilemma is in the
      management of patients with large aneurysm which require an urgent repair and
      presented with concomitant pathologies that carry a high risk of sepsis. In this
      case report, we described an unusual presentation of a large aneurysm with a
      concomitant divirticular abscess where both needed an urgent intervention.

PMID- 25598399
TI  - Autonomic dysreflexia during cystolitholapaxy in patients with spinal cord
      injury.
AB  - AIM: This study aims to explore the risk factors associated with autonomic
      dysreflexia (AD) reflex during cystolitholapaxy and increase the awareness of
      urologists on the dangerous reaction of AD in patients with spinal cord injury
      (SCI). METHODS: Data of 89 SCI patients with bladder stone who underwent
      cystolitholapaxy were retrospectively analyzed. Patients were divided into two
      groups according to the presence or absence of AD. Risk factors may associated
      with AD during the endoscopic procedure were analyzed by comparing clinical and
      operative features between the two groups. RESULTS: Of the 89 patients, 31
      (34.83%) developed AD during the procedure. The patients who developed AD had
      larger stones (4.58+/-1.26 cm vs. 3.75+/-1.15 cm, P<0.01), more stones (2.29+/
      0.86 vs. 1.74+/-0.81, P<0.01), and greater injury (83.87% vs. 41.38%, above T6,
      P<0.01) than those who did not develop AD. The patients who developed AD suffered
      higher irrigation (83.55+/- 13.05 cm vs. 77.47+/-10.91 cm, P<0.05) and longer
      operation time (60.65+/-17.78 min vs. 49.31+/-14.31 min, P<0.01) than those who
      did not develop AD. The AD group also received local anesthetics to a larger
      extent compared with non-AD group, which more often had spinal anesthesia.
      CONCLUSION: The patients who developed AD during the procedure had larger stones,
      more stone number, injury level more often above T6, higher hydraulic irrigation
      height, and longer operation time compared with the patients who did not develop
      AD. Urologists should pay extra care when performing cystolitholapaxy on
      individuals with these features.

PMID- 25598401
TI  - Peritonectomy and hyperthermic intraperitoneal chemotherapy as treatment for
      desmoplastic small round cell tumour.
AB  - INTRODUCTION: The St George Hospital specialises in peritonectomy and
      hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of intra
      abdominal malignancies. Despite performing around 800 peritonectomy and HIPEC
      procedures, we have rarely encountered desmoplastic small round cell tumours
      (DSRCT). We present our experiences with DSRCT, and propose peritonectomy and
      HIPEC as a treatment option for DSRCT. PRESENTATION OF CASE: This is a case
      series of 3 cases. The first case was a 26-year-old male who presented with
      appendicitis which we diagnosed as DSRCT and treated with peritonectomy and
      HIPEC. The second case was a 14-year-old male referred to our centre for
      peritonectomy and HIPEC after initial presentation with a pelvic mass and
      treatment with chemotherapy. The third case was a 21-year-old male referred to
      our centre for peritonectomy and HIPEC for recurrent DSRCT after previously being
      treated with neoadjuvant chemotherapy and surgery without HIPEC. DISCUSSION:
      DSRCT is a rare, almost exclusively intra-abdominal malignancy, which
      predominantly affects young males. Survival prognosis remains poor in DSRCT
      despite conventional treatment with surgery, chemotherapy and radiotherapy;
      however, HIPEC has offered promising survival results. Our recurrences with
      peritonectomy and HIPEC at 6 months and 15 months are comparable with the
      literature of 8.85 months. CONCLUSION: In our experience, patients with DSRCT who
      present with nodal involvement or recurrent disease tend to recur early despite
      treatment with peritonectomy and HIPEC. Longer term follow up of our patients and
      future studies involving HIPEC in DSRCT would be useful in assessing long-term
      clinical outcomes and survival.

PMID- 25598402
TI  - Surgical management of haemorrhaging renal angiomyolipoma in pregnancy.
AB  - INTRODUCTION: Renal angiomyolipoma (AML) is a benign mesenchymal tumour of the
      kidney with a tendency of aneurysm formation at risk of rupturing. Due to
      increased maternal circulation and hormonal influences, rupture risk is greater
      in pregnancy, often leading to a vascular emergency and premature delivery or
      termination. PRESENTATION OF CASE: A 24-weeks pregnant woman (45 years old, G6P1)
      presented with haematuria and flank pain. CT showed AML with acute haemorrhage.
      The patient became haemodynamically unstable and underwent urgent embolisation
      and follow-on total radical nephrectomy with the foetus being left in-utero. This
      involved a multidisciplinary team (urologist, vascular surgeon, interventional
      radiologist and obstetrician). The procedure was uncomplicated and the pregnancy
      went to term with a healthy girl delivered at 38 weeks. DISCUSSION: The incidence
      of AML is 0.13% in the general population. 21 reports of haemorrhaging AML in
      pregnancy have been published in the last 35 years. Mean gestational age was 29.6
      weeks. Eight were treated conservatively to term, one underwent exploratory
      laparotomy with evacuation of haematoma only, five were embolised, and seven were
      managed with nephrectomy. Of the nephrectomy subgroup, one was preceded by
      vaginal delivery and five underwent concurrent caesarean section (one with pre-op
      embolisation). There were two associated foetal deaths. CONCLUSION: This case
      demonstrates that with a multidisciplinary approach, it is possible to
      successfully leave a foetus undelivered whilst performing a radical nephrectomy
      for a large bleeding AML in a woman carrying a late second trimester pregnancy.

PMID- 25598403
TI  - A case of retroperitoneal liposarcoma after delivery with expression of estrogen
      receptor: Report of a case.
AB  - INTRODUCTION: Liposarcoma is one of the most common soft tissue sarcomas;
      however, early diagnosis is rare as the tumor remains difficult and unpalpable
      for a prolonged period of time. PRESENTATION OF CASE: Here we report the first
      case of retroperitoneal liposarcoma associated with pregnancy and expression of
      estrogen receptor. A 34-year-old woman experienced persistent abdominal
      distension after her first delivery. Computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed a large (40cm*35cm), solid, palpable abdominal
      mass with fat attenuation displacing the ascending colon and the right kidney to
      the left. Laparotomy and an en-bloc resection of the tumor were performed;
      further, right nephrectomy and adrenalectomy were required. Histopathology showed
      a well-differentiated liposarcoma; approximately 10-20% of the tumor cells were
      ER-positive. DISCUSSION: Retroperitoneal liposarcoma associated with pregnancy is
      an extremely rare occurrence. Surgical resection is unquestionably the first
      choice of treatment, but complete resection is sometimes impossible due to the
      volume and depth of invasion of the tumor. In such cases, additional therapy for
      liposarcoma is important to improve prognosis. Thus, this report highlights the
      need for further research into hormone therapy. CONCLUSION: Retroperitoneal
      liposarcoma has a high local recurrence rate due to the difficulty in complete
      surgical resection; therefore, additional hormone therapy is important for
      improving the prognosis.

PMID- 25598404
TI  - Templating carbohydrate-functionalised polymer-scaffolded dynamic combinatorial
      libraries with lectins.
AB  - A conceptually new approach to the design of macromolecular receptors for lectins
      is outlined. Carbohydrate-functionalised Polymer-Scaffolded Dynamic Combinatorial
      Libraries (PS-DCLs) have been prepared in aqueous solution by the reversible
      conjugation of carbohydrates possessing acylhydrazide functionalities in their
      aglycone on to an aldehyde-functionalised polymer scaffold. PS-DCLs have been
      shown to undergo compositional change in response to the addition of lectin
      templates, with polymer scaffolds preferentially incorporating carbohydrate units
      which recognise the lectin added. This compositional change has been shown to
      generate polymers of significantly enhanced affinity for the lectin added, with
      enhancements in free energy of binding in the range of 5.2-8.8 kJ mol(-1)
      observed. Experiments indicate that these enhancements are not only as a
      consequence of increased display of the preferred carbohydrate upon the polymer
      scaffold, but that templation also reorganises key residues into strategic
      positions in order to interact more strongly with the target. 

PMID- 25598405
TI  - Portal hypertension and the outcome of surgery for hepatocellular carcinoma in
      compensated cirrhosis: A systematic review and meta-analysis. More doubts than
      clarity.

PMID- 25598406
TI  - Broadband photodetectors based on graphene-Bi2Te3 heterostructure.
AB  - Recently, research on graphene based photodetectors has drawn substantial
      attention due to ultrafast and broadband photoresponse of graphene. However, they
      usually have low responsivity and low photoconductive gain induced by the gapless
      nature of graphene, which greatly limit their applications. The synergetic
      integration of graphene with other two-dimensional (2D) materials to form van der
      Waals heterostructure is a very promising approach to overcome these
      shortcomings. Here we report the growth of graphene-Bi2Te3 heterostructure where
      Bi2Te3 is a small bandgap material from topological insulator family with a
      similar hexagonal symmetry to graphene. Because of the effective photocarrier
      generation and transfer at the interface between graphene and Bi2Te3, the device
      photocurrent can be effectively enhanced without sacrificing the detecting
      spectral width. Our results show that the graphene-Bi2Te3 photodetector has much
      higher photoresponsivity (35 AW(-1) at a wavelength of 532 nm) and higher
      sensitivity (photoconductive gain up to 83), as compared to the pure monolayer
      graphene-based devices. More interestingly, the detection wavelength range of our
      device is further expanded to near-infrared (980 nm) and telecommunication band
      (1550 nm), which is not observed on the devices based on heterostructures of
      graphene and transition metal dichalcogenides. 

PMID- 25598408
TI  - Trueness and comparability assessment of widely used assays for 5 common enzymes
      and 3 electrolytes.

PMID- 25598409
TI  - Quantitative amino acid analysis by liquid chromatography-tandem mass
      spectrometry: implications for the diagnosis of argininosuccinic aciduria.

PMID- 25598410
TI  - The common link between functional somatic syndromes may be central
      sensitisation.
AB  - OBJECTIVES: Functional somatic syndromes are common and disabling conditions that
      all include chronic pain, and which may be related to central nervous system
      sensitisation. Here, we address the concept of central sensitisation as a
      physiological basis for the functional somatic syndromes. METHODS: A narrative
      review of the current literature on central sensitisation and physiological
      studies in the functional somatic syndromes. RESULTS: Central sensitisation may
      be a common neurophysiological process that is able to explain non-painful as
      well as painful symptoms in these disorders. Furthermore, central sensitisation
      may represent an endophenotypic vulnerability to the development of these
      syndromes that potentially explains why they cluster together. CONCLUSIONS:
      Further research is needed to verify these findings, including prospective
      studies and the standardisation of combined methods of investigation in the study
      of central sensitisation in functional somatic syndromes. In turn, this may lead
      to new explanatory mechanisms and treatments being evaluated. Our conclusions add
      to the debate over the nomenclature of these syndromes but importantly also
      provide an explanation for our patients.

PMID- 25598411
TI  - Introducing stage-specific spatial distribution into the Levins metapopulation
      model.
AB  - The Levins model is a classical but still widely used metapopulation model that
      describes temporal changes in the regional abundance of a species by extinction
      and colonization of subpopulations. A fundamental assumption of the model is that
      the landscape is homogeneous and the species moves between identical patches at
      random. However, this assumption clearly contrasts with the common observation
      that different stages prefer or require different habitat types. Here I studied a
      minimum extension of the Levins model in which the species has stage-specific
      (juvenile and adult) spatial distributions and dispersal occurs at the timing of
      reproduction and maturation (i.e., ontogenetic habitat shifts). I examined how
      the persistence of the stage-structured metapopulations would be affected by
      rescue effect and interspecific competition. The models predict that rates of
      ontogenetic habitat shifts are particularly crucial for the persistence or
      coexistence of stage-structured metapopulations because the species need to
      complete biphasic life cycles. The present study opens a new avenue for exploring
      stage- and space-structured population dynamics and will contribute to better
      landscape management for the conservation of stage-structured animals. 

PMID- 25598412
TI  - Solid-phase cyclopalladation in S,C,S'-pincer systems: rising alternative for
      synthesis in solution.
AB  - In pursuit of a new and simple approach to complex organometallic systems, the
      possibility of formation of a palladium-carbon bond in the solid state via direct
      cyclopalladation has been studied toward several S,C,S'-pincer ligands with
      thione sulfur donors of different nature. It is found that mixtures of the ligand
      and PdCl2(NCPh)2 obtained by the manual grinding of reactants in a mortar
      efficiently undergo solid-phase cyclometalation upon heating in open test tubes
      without the addition of a solvent to afford the desired pincer-type products in
      high yields. In the case of the most active bis(thiocarbamoyl) ligand, solid
      phase cyclopalladation proceeds even at room temperature. For the challenging
      bis(thiophosphoryl) derivative, the preformed non-metallated complexes can be
      successfully used as a starting material to essentially enhance the yield of the
      desired pincer complex compared to the conventional synthesis in solution. The
      solid-phase transformation is followed by IR spectroscopy and SEM analysis. The
      results obtained show that the suggested solid-phase methodology can serve as a
      powerful alternative to conventional synthesis of pincer complexes in solution. 

PMID- 25598407
TI  - Applications of mass spectrometry for cellular lipid analysis.
AB  - Mass spectrometric analysis of cellular lipids is an enabling technology for
      lipidomics, which is a rapidly-developing research field. In this review, we
      briefly discuss the principles, advantages, and possible limitations of
      electrospray ionization (ESI) and matrix assisted laser desorption/ionization
      (MALDI) mass spectrometry-based methodologies for the analysis of lipid species.
      The applications of these methodologies to lipidomic research are also
      summarized. 

PMID- 25598413
TI  - mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes.
AB  - Cell fate specifications of multiciliate cells (MCCs) and ionocytes are commonly
      suppressed by the Notch pathway in developing epithelia, but are governed by
      different master regulators, suggesting the existence of a common regulator
      linking the Notch pathway to both MCC and ionocyte specifications. Here we show
      that a mab21 family gene, mab21-l3, represents the missing link. In Xenopus
      embryonic epidermis, mab21-l3 expression is specifically found in MCCs and
      ionocytes and is downregulated by the Notch pathway. Knockdown of mab21-l3 in
      Xenopus downregulates both MCC-specific and ionocyte-specific master genes,
      resulting in drastic loss of MCCs and ionocytes. In mouse tracheal epithelial
      cells, mab21-l3 expression is also downregulated by the Notch pathway and is
      required for MCC differentiation. Moreover, conditional gain of function of mab21
      l3 rescues Notch-induced loss of MCCs and ionocytes in Xenopus. These results
      indicate that mab21-l3 acts downstream of the Notch pathway in cell fate
      specifications of MCCs and ionocytes. 

PMID- 25598414
TI  - Target profiling of zerumbone using a novel cell-permeable clickable probe and
      quantitative chemical proteomics.
AB  - Zerumbone is a phytochemical with diverse biological activities ranging from anti
      inflammatory to anti-cancer properties; however, to date the cellular targets of
      this important compound have remained elusive. Here we report the global protein
      target spectrum of zerumbone in living cancer cells using competitive activity
      based protein profiling of a novel cell-permeable clickable probe, combined with
      quantitative mass spectrometry. 

PMID- 25598415
TI  - Preventing maternal deaths and overcoming challenges related to disability in
      pregnant women.

PMID- 25598416
TI  - Oxytocin mechanisms of stress response and aggression in a territorial finch.
AB  - All jawed vertebrates produce a form of oxytocin (OT), and in birds, mammals and
      fish, OT is strongly associated with affiliation. However, remarkably few data
      are available on the roles of OT and OT receptors (OTRs) in aggression. Because
      OT and OTRs exert anxiolytic effects in mammals (although context-specific) and
      modulate stress coping, we hypothesized that OTR activation is at least
      permissive for territorial aggression. Indeed, we find that peripheral injections
      of an OTR antagonist significantly reduce male-male and female-female aggression
      in a highly territorial finch. This finding suggests the hypothesis that
      aggression is accompanied by an increase in transcriptional (Fos) activity of OT
      neurons, but contrary to this hypothesis, we find that dominant male residents do
      not elevate OT-Fos colocalization following an aggressive encounter and that OT
      Fos colocalization in the preoptic area and hypothalamus correlates negatively
      with aggression. Furthermore, OT-Fos colocalization increases dramatically in
      males that were aggressively subjugated or pursued by a human hand, likely
      reflecting OT modulation of stress response. Because OT inhibits the hypothalamo
      pituitary-adrenal axis, the antagonist effects may reflect the fact that
      aggressive birds and mammals tend to be hyporesponsive to stress. If this is
      correct, then 1) the observed effects of OTR antagonism may reflect alterations
      in corticosterone feedback to the brain rather than centrally mediated OTR
      effects, and 2) the negative correlation between OT-Fos colocalization and
      aggression may reflect the fact that more aggressive, stress hyporesponsive males
      require less inhibition of the hypothalamo-pituitary-adrenal axis than do less
      aggressive males, despite the requirement of that inhibition for the normal
      display of aggression. 

PMID- 25598418
TI  - Radiation exposure in scoliosis surgery: freehand technique versus image
      guidance.

PMID- 25598417
TI  - Dendritic neurosecretion phenomenon of olfactory receptor cells.

PMID- 25598419
TI  - Glibenclamide for acute brain edema. Is the good news coming?

PMID- 25598421
TI  - MiR125a-5p acting as a novel Gab2 suppressor inhibits invasion of glioma.
AB  - Poor prognosis of glioma is due to the characteristics of high invasiveness.
      Recently, it was demonstrated that Gab2 was over-expressed and related to
      cellular migration and invasion in glioma, however, the mechanisms of regulation
      are still unknown. A better understanding of molecular events key to the
      carcinogenesis and tumor progression may facilitate development of new
      therapeutic targets and anti-glioma strategies. This study is the first to focus
      on miR125a-5p, which was predicted to regulate Gab2 with directly targeting the
      3' un-translated region (3'UTR) of Gab2 and could inhibit migration and invasion
      of glioma cells by mediating Gab2 to affect cytoskeleton rearrangement and matrix
      metalloproteinases expression. Interestingly, further evaluation revealed that
      the miR125a-5p promoter was hypermethylated and that attenuating promoter
      methylation was sufficient to up-regulate miR125a-5p expression in glioma cells.
      Additionally, we reported that miR125a-5p was down-regulated in glioma as well as
      statistical analysis suggested that its expression level correlated with the
      World Health Organization grades of glioma (P < 0.05) and that patients with a
      low miR125a-5p level exhibited shorter survival time (P < 0.05). Taken together,
      these results reveal that miR125a-5p represents potential therapeutic targets in
      glioma by modulating Gab2.

PMID- 25598420
TI  - Hydrophobic interaction mediating self-assembled nanoparticles of succinobucol
      suppress lung metastasis of breast cancer by inhibition of VCAM-1 expression.
AB  - The prevention and treatment of lung metastasis of breast cancer remain a major
      challenge. The vascular cell adhesion molecule-1 (VCAM-1) could provide a
      potential therapeutic target in lung metastasis. Herein, succinobucol (SCB), a
      water-insoluble potent and selective VCAM-1 inhibitor, was assembled with
      triblock polymer poloxamer P188 into nanoparticles due to the intermolecular
      hydrophobic interactions. The experimental results showed that the SCB loaded
      nanoparticles (SN) could greatly improve the oral delivery and suppress the lung
      metastasis of breast cancer. The cell migration and invasion abilities of
      metastatic 4T1 breast cancer cells were obviously inhibited by SN. Moreover, the
      VCAM-1 expression on 4T1 cells was significantly reduced by SN, and the cell-cell
      binding ratio of RAW 264.7 cells to 4T1 cells greatly decreased from 47.4% to
      3.2%. Furthermore, the oral bioavailability of SCB was greatly improved about 13
      fold by SN, and the biodistribution in major organs was evidently enhanced. In
      particular, in the metastatic breast cancer model, the lung metastasis was
      notably reduced by SN treatment, and the VCAM-1 expression in lung tissues was
      significantly inhibited. Thereby, SN could evoke a new effective therapeutic
      efficacy of SCB on lung metastasis of breast cancer by inhibition of VCAM-1
      expression. 

PMID- 25598422
TI  - Umeclidinium/vilanterol combination inhaler efficacy and potential impact on
      current chronic obstructive pulmonary disease management guidelines.
AB  - INTRODUCTION: Umeclidinium bromide (UM) with vilanterol (VI) is the first once
      daily long-acting muscarinic antagonist/long-acting beta2 agonist (LAMA/LABA)
      combination approved for use in the treatment of chronic obstructive pulmonary
      disease (COPD) in the USA. Prior to this, only combinations of short-acting
      bronchodilators and short-acting muscarinic antagonists were available in the USA
      as a single inhaler and they required frequent dosing. LAMA or LABA therapy is
      the recommended first choice for moderate-to-very severe COPD with combination
      therapy added if monotherapy fails to control patients' symptoms. This allows
      lower dosing of individual medications, which may limit adverse effects. It could
      also have the additional benefit of improving patient compliance by making
      medication regimens less laboring. AREAS COVERED: A comprehensive literature
      search of journal articles and abstracts looking for trials that evaluated both
      the efficacy and the safety of UM/VI revealed that UM/VI improves patients' lung
      function and overall health status, while maintaining excellent safety and
      tolerability profiles compared to placebo and other bronchodilators. EXPERT
      OPINION: Given the clinical efficacy, favorable safety profile and ease of use,
      clinicians may recommend UM/VI to patients with moderate-to-very severe COPD - a
      shift that could have significant impact on the management of COPD.

PMID- 25598424
TI  - Hydatid cyst disease of the thyroid gland: report of two cases.
AB  - Hydatid cyst disease may develop in any organ of the body, most frequently in the
      liver and lung, but occasionally can affect other organs such as the thyroid
      gland. Although the prevalence of thyroidal cyst disease varies by region,
      literature data suggest that it ranges between 0% and 3.4%. The aim of this
      report was to share 2 cases with thyroid hydatid cyst. Two female patients aged
      26 and 57 years were admitted to our outpatient clinic with different complaints.
      While the first case presented with front of the neck swelling and pain, the
      second case presented with hoarseness, sore throat, and neck swelling. Both
      patients were living in a rural area in the southeastern region of Turkey and had
      had a long history of animal contact. Both patients had undergone previous
      surgeries for hydatid cyst disease. Both patients presented with a clinical
      picture consistent with typical multinodular goiter, and both underwent total
      thyroidectomy after detailed examinations and tests. The exact diagnosis was made
      after histopathologic examination in both patients. They both had a negative
      indirect hemagglutination test studied from blood samples. They both have had no
      recurrences during a 4-year follow-up. In conclusion, although thyroid gland is
      rarely affected, hydatid cyst disease should not be overlooked in differential
      diagnosis of cystic lesions of thyroid gland in patients who live in regions
      where hydatid cyst disease is endemic and who had hydatid cysts in other regions
      of their body. 

PMID- 25598426
TI  - Sex differences in depressive and socioemotional responses to an inflammatory
      challenge: implications for sex differences in depression.
AB  - Substantial evidence demonstrates that inflammatory processes may underlie
      depression for a subset of patients, including work showing that healthy subjects
      exposed to an inflammatory challenge show increases in depressed mood and
      feelings of social disconnection. However, despite the fact that depression is
      two times as likely to occur in females than males, the vast majority of this
      work has been carried out in males. Thus, the objective of this study was to
      determine whether females (vs males) would show greater increases in
      proinflammatory cytokines, depressed mood, and social disconnection in response
      to an inflammatory challenge. One hundred and fifteen healthy participants (69
      female) completed this double-blind, placebo-controlled, randomized clinical
      trial in which participants were randomly assigned to receive either a single
      infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body
      weight) or placebo (same volume of 0.9% saline). Interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), depressed mood, and feelings of social
      disconnection were assessed hourly. Results showed that endotoxin (vs placebo)
      led to increases in proinflammatory cytokines (TNF-alpha, IL-6), depressed mood,
      and feelings of social disconnection. Females exposed to endotoxin showed greater
      increases in depressed mood and feelings of social disconnection. Furthermore,
      increases in TNF-alpha and IL-6 were correlated with increases in social
      disconnection for females but not for males. These sex differences in the
      relationships between inflammatory and socioemotional responses to an
      inflammatory challenge may be particularly important for understanding why
      females are two times as likely as males to develop depressive disorders.

PMID- 25598425
TI  - Advanced research on vasculogenic mimicry in cancer.
AB  - Vasculogenic mimicry (VM) is a brand-new tumour vascular paradigm independent of
      angiogenesis that describes the specific capacity of aggressive cancer cells to
      form vessel-like networks that provide adequate blood supply for tumour growth. A
      variety of molecule mechanisms and signal pathways participate in VM induction.
      Additionally, cancer stem cell and epithelial-mesenchymal transitions are also
      shown to be implicated in VM formation. As a unique perfusion way, VM is
      associated with tumour invasion, metastasis and poor cancer patient prognosis.
      Due to VM's important effects on tumour progression, more VM-related strategies
      are being utilized for anticancer treatment. Here, with regard to the above
      aspects, we make a review of advanced research on VM in cancer. 

PMID- 25598428
TI  - Prefrontal thinning affects functional connectivity and regional homogeneity of
      the anterior cingulate cortex in depression.
AB  - Major depressive disorder (MDD) is associated with structural and functional
      alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC).
      Enhanced ACC activity at rest (measured using various imaging methodologies) is
      found in treatment-responsive patients and is hypothesized to bolster treatment
      response by fostering adaptive rumination. However, whether structural changes
      influence functional coupling between fronto-cingulate regions and ACC regional
      homogeneity (ReHo) and whether these functional changes are related to levels of
      adaptive rumination and treatment response is still unclear. Cortical thickness
      and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy
      controls. Regions with reduced cortical thickness defined the seeds for the
      subsequent functional connectivity (FC) analyses. Patients completed the Response
      Style Questionnaire, which provided a measure of adaptive rumination associated
      with better response to psychotherapy. Compared with controls, depressed patients
      showed thinning of the right anterior PFC, increased prefrontal connectivity with
      the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of
      increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo
      scores positively correlated with PFC thickness and with FC strength. Moreover,
      stronger fronto-cingulate connectivity was related to higher levels of adaptive
      rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem
      to foster adaptive forms of self-referential processing associated with better
      response to psychotherapy, whereas prefrontal thinning impairs the ability of
      depressed patients to engage the suACC during a major depressive episode.
      Bolstering the function of the suACC may represent a potential target for
      treatment. 

PMID- 25598427
TI  - Sex moderates the effects of the Sorl1 gene rs2070045 polymorphism on cognitive
      impairment and disruption of the cingulum integrity in healthy elderly.
AB  - The SORL1 rs2070045 polymorphism was reported to be associated with SorLA
      expression in the brain and the risk of late-onset Alzheimer's disease (AD).
      However, the influence of this polymorphism on cognitive functioning is likely to
      be moderated by sex. This study aimed to examine the sex moderation on the
      effects of rs2070045 on neuropsychological performance and the cingulum integrity
      in Chinese Han population. In this study, 780 non-demented older adults completed
      a battery of neuropsychological scales. Diffusion tensor images (DTI) of 126
      subjects were acquired. We adopted the atlas-based segmentation strategy for
      calculating the DTI indices of the bilateral cingulum and cingulum hippocampal
      part for each subject. We used a multivariate analysis of variance (MANOVA) to
      compare the cognitive performance and DTI differences between the rs2070045
      genotype. Controlling for age, education, and the APOE E4 status, the influence
      of sex on the effects of the rs2070045 polymorphism on executive function was
      observed. We also found an interaction between sex and the rs2070045 polymorphism
      on the white matter (WM) microstructure of the left cingulum hippocampal part.
      Furthermore, the mean diffusivity and axial diffusivity of the tract were
      associated with Trail Making Test performance in T/T men. These results hint that
      sex moderates the association between the rs2070045 polymorphism and executive
      function, as well as the WM integrity of the left cingulum hippocampal part. Our
      findings underscore the importance of considering the influence of sex when
      examining the candidate genes for cognitive abilities and AD. 

PMID- 25598429
TI  - Maternal care differentially affects neuronal excitability and synaptic
      plasticity in the dorsal and ventral hippocampus.
AB  - Variations in early life maternal care modulate hippocampal development to
      program distinct emotional-cognitive phenotypes that persist into adulthood.
      Adult rat offspring that received low compared with high levels of maternal
      licking and grooming (low LG offspring) in early postnatal life show reduced long
      term potentiation (LTP) and impaired hippocampal-dependent memory, suggesting a
      'detrimental' maternal effect on neural development. However, these studies
      focused uniquely on the dorsal hippocampus. Emerging evidence suggests a distinct
      role of the ventral hippocampus in mediating aggression, anxiety, and fear-memory
      formation, which are enhanced in low LG offspring. We report that variations in
      maternal care in the rat associate with opposing effects on hippocampal function
      in the dorsal and ventral hippocampus. Reduced pup licking associated with
      suppressed LTP formation in the dorsal hippocampus, but enhanced ventral
      hippocampal LTP. Ventral hippocampal neurons in low LG offspring fired action
      potentials at lower threshold voltages that were of larger amplitude and faster
      rise rate in comparison with those in high LG offspring. Furthermore, recordings
      of excitatory postsynaptic potential-to-spike coupling (E-S coupling) revealed an
      increase in excitability of ventral hippocampal CA1 neurons in low LG offspring.
      These effects do not associate with changes in miniature excitatory postsynaptic
      currents or paired-pulse facilitation, suggesting a specific effect of maternal
      care on intrinsic excitability. These findings suggest region-specific influences
      of maternal care in shaping neural development and synaptic plasticity. 

PMID- 25598431
TI  - Serum antibodies from epileptic patients react, at high prevalence, with simian
      virus 40 mimotopes.
AB  - BACKGROUND AND PURPOSE: It has been demonstrated that inflammation may contribute
      to epileptogenesis and cause neuronal injury in epilepsy. In this study, the
      prevalence of antibodies to simian virus 40 (SV40), a kidney and neurotropic
      polyomavirus, was investigated in serum samples from 88 epileptic
      children/adolescents/young adults. METHODS: Serum antibodies reacting to specific
      SV40 peptides were analysed by indirect enzyme-linked immunosorbent assay.
      Synthetic peptides corresponding to the epitopes of viral capsid proteins 1-3
      were used as SV40 antigens. RESULTS: A significantly higher prevalence of
      antibodies against SV40 was detected in sera from epileptic patients compared to
      controls (41% vs. 19%). Specifically, the highest significant difference was
      revealed in the cohort of patients from 1.1 to 10 years old (54% vs. 21%), with a
      peak in the sub-cohort of 3.1-6 years old (65% vs. 18%). CONCLUSION: Our
      immunological data suggest a strong association between epilepsy and the SV40
      infection.

PMID- 25598432
TI  - Approaches to influencing food choice across the age groups: from children to the
      elderly.
AB  - Nutrition across the lifespan encompasses both preventative and treatment options
      to maintain health and vitality. This review will focus on the challenge of
      overconsumption of energy relative to energy expenditure and the consequent
      development of overweight and obesity, since they are responsible for much of the
      burden of chronic disease in the developed world. Understanding the mechanisms of
      hunger and satiety and how particular foodstuffs and nutrients affect appetite
      and motivation to eat is important for evidence-based interventions to achieve
      weight control and design of community-wide dietary strategies that reach across
      the lifespan. Food reformulation for appetite control and weight management
      requires a knowledge of the mechanisms of hunger and satiety, how food interacts
      with peripheral and central regulatory systems, and how these interactions change
      across the lifecourse, allied to the technical capability to generate, evaluate
      and develop new ingredients and foods with enhanced biological potency based on
      these mechanisms. Two European Union-funded research projects, Full4Health and
      SATIN, are adopting these complementary approaches. These research projects
      straddle the sometimes conflicted ground between justifiable public health
      concerns on the one hand and the food and drink industry on the other. These
      multi-disciplinary projects pull together expertise in nutrition, neuroimaging,
      psychology and food technology that combines with food industry partners to
      maximise expected impact of the research. Better knowledge of mechanisms
      regulating hunger/satiety will lead to evidence base for preventive strategies
      for the European population, to reduction of chronic disease burden and to
      increased competitiveness of European food industry through the development of
      new food products. 

PMID- 25598433
TI  - Metallo-solid lipid nanoparticles as colloidal tools for meso-macroporous
      supported catalysts.
AB  - Meso-macroporous silica containing iron oxide nanoparticles (15-20 nm) was
      synthesized by formulating solid lipid nanoparticles and metallosurfactant as
      both template and metal source. Because of the high active surface area of the
      catalyst, the material exhibits an excellent performance in a Fenton-like
      reaction for methylene blue (MB) degradation, even at low amount of iron oxide
      (5% TOC after 14 h). 

PMID- 25598434
TI  - Binding constant determination of uranyl-citrate complex by ACE using a multi
      injection method.
AB  - The binding constant determination of uranyl with small-molecule ligands such as
      citric acid could provide fundamental knowledge for a better understanding of the
      study of uranyl complexation, which is of considerable importance for multiple
      purposes. In this work, the binding constant of uranyl-citrate complex was
      determined by ACE. Besides the common single-injection method, a multi-injection
      method to measure the electrophoretic mobility was also applied. The BGEs used
      contained HClO4 and NaClO4 , with a pH of 1.98 +/- 0.02 and ionic strength of
      0.050 mol/L, then citric acid was added to reach different concentrations. The
      electrophoretic mobilities of the uranyl-citrate complex measured by both of the
      two methods were consistent, and then the binding constant was calculated by
      nonlinear fitting assuming that the reaction had a 1:1 stoichiometry and the
      complex was [(UO2 )(Cit)](-) . The binding constant obtained by the multi
      injection method was log K = 9.68 +/- 0.07, and that obtained by the single
      injection method was log K = 9.73 +/- 0.02. The results provided additional
      knowledge of the uranyl-citrate system, and they demonstrated that compared with
      other methods, ACE using the multi-injection method could be an efficient, fast,
      and simple way to determine electrophoretic mobilities and to calculate binding
      constants.

PMID- 25598430
TI  - Genetic variants in one-carbon metabolism genes and breast cancer risk in
      European American and African American women.
AB  - Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis,
      repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs)
      in folate-metabolizing enzymes has been investigated in risk of breast cancer
      among European or Asian populations, but not among women of African ancestry. We
      conducted a comprehensive analysis of SNPs in eleven genes involved in one-carbon
      metabolism and risk of breast cancer in 1,275 European-American (EA) and 1,299
      African-American (AA) women who participated in the Women's Circle of Health
      Study. Allele frequencies varied significantly between EA and AA populations. A
      number of these SNPs, specifically in genes including MTR, MTRR, SHMT1, TYMS and
      SLC19A1, were associated with overall breast cancer risk, as well as risk by
      estrogen receptor (ER) status, in either EA or AA women. Associations appeared to
      be modified by dietary folate intake. Although single-SNP associations were not
      statistically significant after correcting for multiple comparisons, polygenetic
      score analyses revealed significant associations with breast cancer risk. Per
      unit increase of the risk score was associated with a modest 19 to 50% increase
      in risk of breast cancer overall, ER positive or ER negative cancer (all p <
      0.0005) in EAs or AAs. In summary, our data suggest that one-carbon metabolizing
      gene polymorphisms could play a role in breast cancer and that may differ between
      EA and AA women. 

PMID- 25598436
TI  - Cool and warm hybrid white organic light-emitting diode with blue delayed
      fluorescent emitter both as blue emitter and triplet host.
AB  - A hybrid white organic light-emitting diode (WOLED) with an external quantum
      efficiency above 20% was developed using a new blue thermally activated delayed
      fluorescent material, 4,6-di(9H-carbazol-9-yl)isophthalonitrile (DCzIPN), both as
      a blue emitter and a host for a yellow phosphorescent emitter. DCzIPN showed high
      quantum efficiency of 16.4% as a blue emitter and 24.9% as a host for a yellow
      phosphorescent emitter. The hybrid WOLEDs with the DCzIPN host based yellow
      emitting layer sandwiched between DCzIPN emitter based blue emitting layers
      exhibited high external quantum efficiency of 22.9% with a warm white color
      coordinate of (0.39, 0.43) and quantum efficiency of 21.0% with a cool white
      color coordinate of (0.31, 0.33) by managing the thickness of the yellow emitting
      layer. 

PMID- 25598435
TI  - Antifungal activity of extracts from Cynomorium coccineum growing wild in
      Sardinia island (Italy).
AB  - Cynomorium coccineum L. is a non-photosynthetic plant, spread over Mediterranean
      countries, amply used in traditional medicine. The aim of this study was to
      evaluate for the first time the antifungal activity of its extracts. The
      antifungal activity was evaluated using the macrodilution method against Candida
      spp., Cryptococcus neoformans and dermatophyte strains. The methanolic extract
      was very active against C. neoformans, Candida guilliermondii and Candida krusei,
      with minimal inhibitory concentrations (MIC) values of 0.025 mg/mL. This extract
      is more active than fluconazole against C. krusei H9. The influence of methanolic
      extract on the dimorphic transition in Candida albicans was also studied through
      the germ tube inhibition assay. More than 60% of filamentation was inhibited at a
      concentration of 1/4 MIC. These results are preliminary and further studies are
      needed to an eventual use of C. coccineum methanolic extract in the treatments of
      candidiasis and cryptococcosis.

PMID- 25598438
TI  - Prospective relationship between poor sleep and substance-related problems in a
      national sample of adolescents.
AB  - BACKGROUND: Previous studies showed that poor sleep prospectively predicted
      alcohol-related problems and illicit drug use in adolescents and young adults
      (Wong and Brower, 2012; Wong et al., 2010). However, more work needs to be done
      to elucidate the nature of these problems. The purpose of this study was to
      examine whether sleep difficulties and hours of sleep prospectively predicted
      several serious substance-related problems, for example, binge drinking, driving
      under the influence of alcohol, and risky sexual behavior. METHODS: Study
      participants were 6,504 adolescents from the National Longitudinal Study of
      Adolescent Health. Data were collected from interviews and questionnaires. This
      study analyzed data from the first 3 waves of data (T1: 1994 to 1995; T2: 1996;
      T3: 2001 to 2002). In all analyses, we used sleep difficulties at a previous wave
      to predict substance-related problems at a subsequent wave, while controlling for
      substance-related problems at a previous wave. RESULTS: Holding T1 alcohol
      related problems constant, sleep difficulties at T1 significantly predicted
      alcohol-related interpersonal problems, binge drinking, gotten drunk or very high
      on alcohol, driving under the influence of alcohol, getting into a sexual
      situation one later regretted due to drinking, ever using any illicit drugs, and
      drug-related problems at T2. T1 hours of sleep negatively predicted T2 alcohol
      related interpersonal problems and binge drinking. The relationship between T2
      sleep variables and T3 substance-related problems was consistent with previous
      waves, although the effect was weaker. CONCLUSIONS: Sleep difficulties and hours
      of sleep are a significant predictor of a number of substance-related problems.
      It may be useful to educate adolescents about the importance of sleep, sleep
      hygiene, and the potential consequences of poor sleep on drinking and related
      behaviors.

PMID- 25598437
TI  - Single-cell mass cytometry reveals intracellular survival/proliferative signaling
      in FLT3-ITD-mutated AML stem/progenitor cells.
AB  - Understanding the unique phenotypes and complex signaling pathways of leukemia
      stem cells (LSCs) will provide insights and druggable targets that can be used to
      eradicate acute myeloid leukemia (AML). Current work on AML LSCs is limited by
      the number of parameters that conventional flow cytometry (FCM) can analyze
      because of cell autofluorescence and fluorescent dye spectral overlap. Single
      cell mass cytometry (CyTOF) substitutes rare earth elements for fluorophores to
      label antibodies, which allows measurements of up to 120 parameters in single
      cells without correction for spectral overlap. The aim of this study was the
      evaluation of intracellular signaling in antigen-defined stem/progenitor cell
      subsets in primary AML. CyTOF and conventional FCM yielded comparable results on
      LSC phenotypes defined by CD45, CD34, CD38, CD123, and CD99. Intracellular
      phosphoprotein responses to ex vivo cell signaling inhibitors and cytokine
      stimulation were assessed in myeloid leukemia cell lines and one primary AML
      sample. CyTOF and conventional FCM results were confirmed by western blotting. In
      the primary AML sample, we investigated the cell responses to ex vivo stimulation
      with stem cell factor and BEZ235-induced inhibition of PI3K and identified
      activation patterns in multiple PI3K downstream signaling pathways including p
      4EBP1, p-AKT, and p-S6, particularly in CD34(+) subsets. We evaluated multiple
      signaling pathways in antigen-defined subpopulations in primary AML cells with
      FLT3-ITD mutations. The data demonstrated the heterogeneity of cell phenotype
      distribution and distinct patterns of signaling activation across AML samples and
      between AML and normal samples. The mTOR targets p-4EBP1 and p-S6 were
      exclusively found in FLT3-ITD stem/progenitor cells, but not in their normal
      counterparts, suggesting both as novel targets in FLT3 mutated AML. Our data
      suggest that CyTOF can identify functional signaling pathways in antigen-defined
      subpopulations in primary AML, which may provide a rationale for designing
      therapeutics targeting LSC-enriched cell populations.

PMID- 25598439
TI  - Dual conical conducting filament model in resistance switching TiO2 thin films.
AB  - The resetting behaviors of Pt/TiO2/Pt resistive switching (RS) cell in unipolar
      RS operations were studied in detail through an experiment and by modeling. The
      experiment showed that the apparently highly arbitrary resetting current-voltage
      (I-V) curves could be grouped into three types: normal, delayed, and abnormal
      behaviors. A dual conical conducting filament (CF) model was conceived, and their
      electrothermal behaviors were analytically described from the heat-balance and
      charge-transport equations. The almost spontaneous resetting behavior of the
      normal reset could be easily understood from the mutually constructive
      interference effect between the Joule heating and temperature-dependent
      resistance effect along the CF. The delayed reset could be explained by the time
      dependent increase in the reset voltage during the rest process, which was most
      probably induced in the more conical-shaped CF. The abnormal reset could be
      understood from the temporal transfer of oxygen ions near the kink positions of
      the two different-diameter portions of the more cylindrical CFs, which temporally
      decreases the overall resistance immediately prior for the actual reset to occur.
      The accuracy of the dual conical CF model was further confirmed by adopting a
      more thorough electrothermal simulation package, COMSOL. 

PMID- 25598442
TI  - Efficient solid-state light-emitting CuCdS nanocrystals synthesized in air.
AB  - Semiconductor nanocrystals (NCs) possess high photoluminescence (PL) typically in
      the solution phase. In contrary, PL rapidly quenches in the solid state.
      Efficient solid state luminescence can be achieved by inducing a large Stokes
      shift. Here we report on a novel synthesis of compositionally controlled CuCdS
      NCs in air avoiding the usual complexity of using inert atmosphere. These NCs
      show long-range color tunability over the entire visible range with a remarkable
      Stokes shift up to about 1.25 eV. Overcoating the NCs leads to a high solid-state
      PL quantum yield (QY) of ca. 55% measured by using an integrating sphere. Unique
      charge carrier recombination mechanisms have been recognized from the NCs, which
      are correlated to the internal NC structure probed by using extended X-ray
      absorption fine structure (EXAFS) spectroscopy. EXAFS measurements show a Cu-rich
      surface and Cd-rich interior with 46% Cu(I) being randomly distributed within 84%
      of the NC volume creating additional transition states for PL. Color-tunable
      solid-state luminescence remains stable in air enabling fabrication of light
      emitting diodes (LEDs).

PMID- 25598441
TI  - The epidemiology and targeted therapies for relapsed and refractory CD30+
      lymphomas.
AB  - BACKGROUND: Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma
      (sALCL) both have consistent expression of CD30, a cytokine receptor that is
      expressed by activated T and B cells but is largely absent from normal tissue.
      METHODS: A literature search was conducted via PubMed, Google Scholar, and
      UpToDate to identify relevant peer-reviewed original research or review articles
      on HL, sALCL, and CD30 targeted therapies. RESULTS: These lymphomas are both more
      common among males, young adults and the elderly. Although many patients with HL
      and sALCL can achieve long-term remission after standard first-line therapy, up
      to a third of these patients are refractory to or relapse after initial therapy.
      Among these relapsed/refractory patients, many experience disease progression
      and/or death despite subsequent treatment, and treatment-related adverse events
      and mortality are not uncommon. To address the need for safer and more effective
      therapies for these relapsed/refractory patients, researchers have developed
      therapies that specifically target CD30-expressing cells. Brentuximab vedotin, an
      antibody-drug conjugate that selectively delivers a toxic microtubule-disrupting
      agent to malignant cells with CD30 expression, is the first such therapy to be
      approved in the US and Europe. In clinical trials, brentuximab vedotin has
      demonstrated efficacy and safety in patients with HL after failure of autologous
      stem cell transplantation (ASCT), or after failure of at least two prior multi
      agent chemotherapy regimens in patients who are not ASCT candidates, and in
      patients with sALCL after failure of at least one prior multi-agent chemotherapy
      regimen. CONCLUSION: HL and sALCL are both CD30+ lymphomas, and therapies like
      brentuximab vedotin that target cells expressing CD30 hold promise for the
      treatment of these diseases.

PMID- 25598443
TI  - Ghosal Syndrome--Ten Years Follow-up.

PMID- 25598440
TI  - The long-acting beta2 -adrenoceptor agonist, indacaterol, enhances glucocorticoid
      receptor-mediated transcription in human airway epithelial cells in a gene- and
      agonist-dependent manner.
AB  - BACKGROUND AND PURPOSE: Inhaled glucocorticoid (ICS)/long-acting beta2 
      adrenoceptor agonist (LABA) combination therapy is a recommended treatment option
      for patients with moderate/severe asthma in whom adequate control cannot be
      achieved by an ICS alone. Previously, we discovered that LABAs can augment
      dexamethasone-inducible gene expression and proposed that this effect may explain
      how these two drugs interact to deliver superior clinical benefit. Herein, we
      extended that observation by analysing, pharmacodynamically, the effect of the
      LABA, indacaterol, on glucocorticoid receptor (GR)-mediated gene transcription
      induced by seven ligands with intrinsic activity values that span the spectrum of
      full agonism to antagonism. EXPERIMENTAL APPROACH: BEAS-2B human airway
      epithelial cells stably transfected with a 2* glucocorticoid response element
      luciferase reporter were used to model gene transcription together with an
      analysis of several glucocorticoid-inducible genes. KEY RESULTS: Indacaterol
      augmented glucocorticoid-induced reporter activation in a manner that was
      positively related to the intrinsic activity of the GR agonist. This effect was
      demonstrated by an increase in response maxima without a change in GR agonist
      affinity or efficacy. Indacaterol also enhanced glucocorticoid-inducible gene
      expression. However, the magnitude of this effect was dependent on both the GR
      agonist and the gene of interest. CONCLUSIONS AND IMPLICATIONS: These data
      suggest that indacaterol activates a molecular rheostat, which increases the
      transcriptional competency of GR in an agonist- and gene-dependent manner without
      apparently changing the relationship between fractional GR occupancy and
      response. These findings provide a platform to rationally design ICS/LABA
      combination therapy that is based on the generation of agonist-dependent gene
      expression profiles in target and off-target tissues.

PMID- 25598444
TI  - Enhancing the management of acute asthma in children: do we have the evidence?

PMID- 25598445
TI  - A Doppler velocimetry evaluation of intestinal blood flow characteristics in
      neonates receiving intravenous immunoglobulin therapy: a prospective
      observational study.
AB  - OBJECTIVES: To evaluate intestinal blood flow changes after intravenous
      immunoglobulin (IVIg) infusion among neonates with Rh isoimmunization and
      alloimmune thrombocytopenia. METHODS: This prospective observational study was
      conducted in level III NICU from July 2011 through August 2012. Thirty three
      consecutive instances (30 neonates) of IVIg treatment (1 g/kg) were studied.
      Celiac (CA) and superior mesenteric artery (SMA) doppler evaluations were
      performed immediately prior (baseline), immediately after and 12 to18 h following
      IVIg infusion. Peak systolic velocity, end diastolic velocity, time-averaged mean
      velocity, pulsatility index, resistive index and systolic/diastolic ratio were
      measured. The doppler indices measured immediately after and 12 to 18 h after
      IVIg infusion were compared with the baseline values. RESULTS: The mean gestation
      and birth weight of the cohort were 36 +/- 2 wk and 2597 +/- 563 g respectively.
      Doppler flow variables measured immediately after and 12 to 18 h after IVIg were
      comparable to baseline values, in both the arteries. However, systolic/diastolic
      ratio in SMA immediately post-IVIg was lower than baseline, [median (IQR): 5 (3,
      9) vs. 7 (4, 14), respectively; p=0.02]. None of the study infants developed feed
      intolerance or necrotizing enterocolitis (NEC). CONCLUSIONS: There was no
      significant change in the celiac and SMA blood flows following IVIg therapy in
      neonates with Rh isoimmunization and alloimmune thrombocytopenia.

PMID- 25598447
TI  - Novel technologies for oral squamous carcinoma biomarkers in diagnostics and
      prognostics.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is a highly prevalent malignant
      pathology of the oral cavity. Despite the significant progress accomplished in
      the field of OSCC, the diagnosis is performed mostly in advanced stages; thus,
      novel biomarkers need to be developed for the diagnostic and prognostic of this
      malignancy. Many new technologies are used to provide indispensable information
      related to the pathogenesis of OSCC. The molecular profiling studies that
      incorporate genetic and epigenetic alterations need to be integrated in clinical
      practice as routine approaches to facilitate a better diagnostic and prognostic.
      REVIEW: In this review, the authors present a summary of these novel technologies
      in the field of genomics, transcriptomics or proteomics, capable of generating
      data related to personalized diagnostic and treatment.

PMID- 25598446
TI  - Use of medications and functional dependence among Chinese older adults in a
      rural community: A population-based study.
AB  - AIM: To investigate the associations between medication use and functional
      dependence in Chinese older people living in a rural community. METHODS: The
      cross-sectional study included 1538 participants (age >=60 years, 59.1% women) in
      the Confucius Hometown Aging Project in Shandong, China. In June 2010 to July
      2011, data on demographics, lifestyle factors, health history, basic activities
      of daily living (ADL), instrumental ADL, and use of medications were collected
      through interviews and clinical examinations. Functional status was categorized
      into no dependence, dependence only in instrumental ADL and dependence in basic
      ADL. Data were analyzed with multinomial logistic models controlling for
      potential confounders. RESULTS: Dependence in instrumental or basic ADL was
      significantly associated with use of antihypertensives and hypolipidemic agents,
      and basic ADL dependence was also associated with use of sedatives or
      tranquilizers and cardiac glycosides. An increased number of concurrently used
      medications was significantly associated with an increased likelihood of
      dependence in basic ADL (P for trend = 0.016). Compared with non-users of any
      medication, individuals who concurrently used three or more classes of
      medications had a multi-adjusted odds ratio of 2.91 (95% confidence interval 1.02
      8.28) for dependence in basic ADL. CONCLUSIONS: Use of antihypertensives,
      hypolipidemic drugs, cardiac glycosides and sedatives or tranquilizers,
      especially use of multiple classes of medications, is correlated with functional
      dependence among older people in rural China. Geriatr Gerontol Int 2015; 15: 1242
      1248.

PMID- 25598448
TI  - Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel
      with pH-responsive release.
AB  - Hyaluronic acid (HA) is made up of repeating disaccharide units (beta-1,4-d
      glucuronic acid and beta-1,3-N-acetyl-d-glucosamine) and is a major constituent
      of the extracellular matrix. HA and its derivatives which possess excellent
      biocompatibility and physiochemical properties have been studied in drug delivery
      and tissue engineering applications. Tyramine-based HA hydrogel with good
      compatibility to cell and tissue has been reported recently. However, inferior
      mechanical property may limit the biomedical application of the HA hydrogel. In
      this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared
      through a horseradish peroxidase catalyzed in situ cross-linking process. As
      compared with pure HA hydrogels, incorporation of GO to the HA matrix could
      significantly enhance the mechanical properties (storage moduli 1800 Pa) of the
      hydrogel and prolong the release of rhodamine B (RB) as the model drug from the
      hydrogel (33 h) as well. In addition, due to the multiple interactions between GO
      and RB, the NC hydrogels showed excellent pH-responsive release behavior. The
      release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the
      presence of GO, which could be attributed to the enhanced interactions between GO
      and HA as well as with RB. In situ three-dimensional encapsulation of mouse
      embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity
      results indicated the cytocompatibility of both the enzymatic cross-linking
      process and HA/GO NC hydrogels (cell viability 90.6 +/- 4.25%). The enzymatically
      catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and
      had great potential in the construction of both tissue engineering scaffolds and
      stimuli-responsive drug release matrices. 

PMID- 25598449
TI  - Neighbourhood and dwelling characteristics associated with the self-reported
      adverse health effects of heat in most deprived urban areas: a cross-sectional
      study in 9 cities.
AB  - Dwelling and neighbourhood characteristics associated with the prevalence of self
      reported heat-induced adverse health effects are not well known. We interviewed
      3485 people in the most disadvantaged neighbourhoods of the nine largest cities
      in Quebec, Canada. The prevalence of heat-induced adverse health effects was 46%,
      out of which one fourth led to medical consultation. Multivariate analyses showed
      that dissatisfaction with the summer dwelling temperature, which refers to home
      heat exposure, and perception that the neighbourhood is polluted due to traffic,
      were determinant, even after adjusting for current health status. These risk
      indicators can be used to identify subgroups at high risk and as priority-setting
      criteria for urban renewal programs for the hotter climate to come. 

PMID- 25598451
TI  - Efficient Exciton Harvesting through Long-Range Energy Transfer.
AB  - Efficient exciton collection at charge-generation sites is one of the key
      requirements for the improvement in power conversion efficiency (PCE) of organic
      solar cells, because only excitons arriving at a donor/acceptor interface can be
      dissociated into free charge carriers. We evaluated the effective diffusion
      length in poly(3-hexylthiophene) (P3HT) by using donor/acceptor bilayers with two
      different exciton-quenching acceptors. One is an insoluble fullerene polymer (p
      PCBVB), which is an efficient electron-accepting material with negligible
      absorption in the visible region. The other is a low-bandgap polymer, poly[(4,4
      bis(2-ethylhexyl)-dithieno[3,2-b:2',3'-d]silole)-2,6-diyl-alt-(2,1,3
      benzothiadiazole)-4,7-diyl], (PSBTBT). This polymer has a large absorption band
      in the near-IR region, which overlaps well with the emission band of P3HT. The
      effective diffusion length of P3HT excitons is evaluated to be 15 nm for P3HT/p
      PCBVB bilayers and improved to 30 nm for P3HT/PSBTBT bilayers. This improvement
      is ascribed to long-range energy transfer from P3HT to PSBTBT. This finding
      suggests that the effective diffusion length of P3HT excitons can be increased
      through long-range energy transfer by incorporating PSBTBT into P3HT/PCBM blends.

PMID- 25598450
TI  - Influence of Testosterone on Inflammatory Response in Testicular Cells and
      Expression of Transcription Factor Foxp3 in T Cells.
AB  - PROBLEM: Previous studies demonstrated a strong association between low androgen
      levels and reduced capacity to mount an inflammatory response. However, the
      mechanisms underlying these observations are largely not understood. METHODS OF
      STUDY: Generation of CD4+CD25+Foxp3+ regulatory T cells in Leydig cell
      conditioned media was determined by flow cytometry and ELISA. Influence of
      testosterone on cytokine response was measured in LPS-stimulated testicular
      macrophages, Sertoli and peritubular cells. RESULTS: Leydig cell-conditioned
      media dose-dependently stimulated expression of transcription factor Foxp3 and
      secretion of IL-10 in splenic CD4+ T cells, an effect abolished by addition of
      the anti-androgen flutamide. In isolated Sertoli and peritubular cells,
      testosterone pre-treatment suppressed the LPS-induced inflammatory response on
      TNF-alpha mRNA expression, while no effect was evident in testicular macrophages
      (TM). CONCLUSIONS: Androgens can influence the immune system under normal
      conditions by the generation and functional differentiation of regulatory T cells
      and in testicular inflammation by direct effect on Sertoli and peritubular cells.

PMID- 25598452
TI  - Biosynthetic origin of E-resveratrol accumulation in grape canes during
      postharvest storage.
AB  - Grape canes are vineyard waste products containing valuable phytochemicals of
      medicine and agriculture interest. Grape canes storage is critical for the
      accumulation of these bioactive compounds. In the present study, we investigated
      the changes in stilbenoid phytochemical composition during grape cane storage and
      the influence of the temperature on final concentrations. A strong increase in
      the concentration of the monomer E-resveratrol (approximately 40-fold) was
      observed during the first 6 weeks of storage at 20  degrees C in eight different
      grape varieties without any change in oligomer concentrations. The E-resveratrol
      accumulation was temperature-dependent with an optimal range at 15-20  degrees C.
      A 2 h heat-shock treatment aiming at protein denaturation inhibited E-resveratrol
      accumulation. The constitutive expression of key genes involved in the stilbene
      precursor biosynthesis along with an induction of stilbene synthase (STS)
      expression during the first weeks of storage contribute to a de novo biosynthesis
      of E-resveratrol in pruned wood grapes.

PMID- 25598454
TI  - Government says it will 'do the right thing' to eradicate bovine TB.

PMID- 25598453
TI  - A randomized, controlled clinical trial of an intravesical pressure-attenuation
      balloon system for the treatment of stress urinary incontinence in females.
AB  - AIMS: Evaluate the efficacy, safety, and tolerability of a novel pressure
      attenuation balloon for the treatment of female stress urinary incontinence (SUI)
      using a prospective, randomized, single-blind, multi-center design, evaluated at
      3 months. METHODS: Sixty-three females with SUI were randomized 2:1 to treatment
      with a balloon (N = 41) or sham procedure (N = 22). The sham (control) entailed
      the same procedure without the deployment of a balloon. Endpoints were evaluated
      at 3 months and included a composite endpoint that required both >=10 point
      increase in the 22-item Incontinence Quality of Life Survey (I-QOL) and >=50%
      decrease in provocative pad weight. Additional endpoints included incontinence
      episode frequency, and PGII assessment. RESULTS: In an ITT analysis, 63% of women
      in the treatment group achieved the composite endpoint, compared to 31% in the
      Control Group (P = 0.0200). In a per protocol analysis, 81% of women in the
      treatment arm had a 50% decrease in pad weight test vs. 45% in the Control Group
      (P = 0.0143); 41.6% of the treatment patients were dry on pad weight test
      (<=1gram) vs. 0% in the Control Group (P < 0.001), and 58% of treated patients
      reported improvement on a PGII assessment versus 25% of women in the Control
      Group (P = 0.025). Adverse events in the treatment group included dysuria
      (14.6%), gross hematuria (9.8%), and UTI (7.3%). CONCLUSIONS: This minimally
      invasive treatment for female SUI with an intravesical pressure-attenuation
      balloon was safe and effective. The concept of pressure attenuation as a therapy
      for SUI is valid and feasible for those patients that can tolerate the balloon.

PMID- 25598455
TI  - MSPs debate use of e-collars in dogs and cats.

PMID- 25598456
TI  - REF results open to various interpretations.

PMID- 25598457
TI  - Time for a change in culture?

PMID- 25598458
TI  - Avian influenza: no clear indication of how H5N8 virus entered the EU.

PMID- 25598459
TI  - Strong support for new specialists' college.

PMID- 25598460
TI  - One Health approach to exploring what drives zoonoses.

PMID- 25598462
TI  - Award for best paper.

PMID- 25598461
TI  - Involving pet owners in setting priorities for research.

PMID- 25598463
TI  - Vets volunteering abroad: seizing opportunities and aligning goals.

PMID- 25598464
TI  - Making sense of uncertainty, risk and chance in public health.

PMID- 25598465
TI  - Equine disease surveillance: quarterly summary.

PMID- 25598466
TI  - Laminitis in the 21st century.

PMID- 25598467
TI  - Selective breeding of non-traditional companion animals.

PMID- 25598468
TI  - Impact of new surveillance plans.

PMID- 25598469
TI  - Vets interested in bee health.

PMID- 25598470
TI  - Commitment to nursing excellence.

PMID- 25598471
TI  - Ten-minute chat.

PMID- 25598473
TI  - Quantum size effects on the optical properties of nc-Si QDs embedded in an a-SiOx
      matrix synthesized by spontaneous plasma processing.
AB  - Quantum confinement effects on optical transitions in ensembles of nc-Si QDs in
      an a-SiOx matrix has become evident by simultaneously considering the dielectric
      function dispersions obtained by optical modeling with spectroscopic
      ellipsometry, the absorption edge, and the photoluminescence peak. Diminution of
      the peak amplitude in the epsilon2-spectra for reducing the diameter of nc-Si QDs
      could arise due to the disappearance of excitonic effects in the E1 transition,
      while the peak broadening indicates an amplification of disorder in Si QDs. An
      energy blue shift happens to take place in an analogous fashion for all the
      characteristic parameters, upon decreasing the size of the nc-Si QDs for
      diameters in the range 6.5 < d < 2.0 nm. The band gap widening with the reduction
      of QD size is well supported by the first-principles calculations based on
      quantum confinement, while studies on the Stokes shift in the optical gap from
      the PL data could provide an understanding of the imperfect passivation of the
      surface defects on tiny nc-Si QDs. Low dimensional nc-Si QDs (~2 nm in diameter)
      assembled in a large density (~2.3 * 10(12) cm(-2)) embedded in an a-SiOx matrix
      synthesized by spontaneous and low-temperature (300  degrees C) RF plasma
      processing, compatible to CMOS technology, are highly conducive for device
      applications. Systematic changes in composition and characteristics, including
      the thickness, of the individual sub-layers of the nc-Si QD thin films can be
      comprehensively pursued through a nondestructive process by ellipsometric
      simulation which could, thereby, enormously contribute to the precise
      optimization of the deposition parameters suitable for specific device
      fabrication e.g., all-silicon tandem solar cells and light emitting diodes, using
      silicon nanotechnology. 

PMID- 25598472
TI  - Common variants identified in genome-wide association studies of testicular germ
      cell tumour: an update, biological insights and clinical application.
AB  - Testicular germ cell tumour (TGCT) is the most common cause of cancer in young
      men (aged 15-45 years) in many populations. Multiple genome-wide association
      studies (GWAS) of TGCT have now been conducted, yielding over 25 disease
      associated single-nucleotide polymorphism (SNP)s at 19 independent loci. The
      genes at these loci have provided rich biological and genetic insight into
      possible mechanisms underlying testicular germ cell oncogenesis. In this review,
      we summarize these mechanisms which can be grouped into five distinct categories:
      KIT/KITLG signalling, other pathways of male germ cell
      development/differentiation, telomerase function, microtubule assembly and DNA
      damage repair. The TGCT risk markers identified through GWAS include individual
      SNPs carrying per allele odds ratios (OR) in excess of 2.5. These ORs are among
      the highest reported in GWAS of any cancer type, hence suggesting a potential
      clinical utility in risk determination. Here, we present analysis of such an
      approach, using polygenic risk scores to calculate the combined effect of all
      risk loci on overall TGCT risk and discuss how a potential screening strategy may
      fit within a broader clinical context. 

PMID- 25598474
TI  - Controlling of water collection ability by an elasticity-regulated bioinspired
      fiber.
AB  - A special artificial spider silk is presented which is fabricated by using both
      an elastic polymer and a fiber, and the water collection behavior is
      investigated. Through exerting tension in varying degree, the length of the three
      phase contact line (TCL) and the area of spindle knot can be regulated readily,
      which makes a great contribution to the improvement of collecting efficiency and
      water-hanging ability. The water-hanging ability can be predicted at a given
      stretching ratio according to the given expression of the TCL. As a result,
      liquid capture or release of distinct measure can be achieved via exerting
      tension. This research is helpful to design smart materials for developing
      applications in fogwater collection, dehumidification, high-efficiency humidity
      control, and controllable adhesion. 

PMID- 25598475
TI  - Introducing seasonal influenza vaccine in low-income countries: an adverse events
      following immunization survey in the Lao People's Democratic Republic.
AB  - OBJECTIVE: In 2012, Lao PDR introduced seasonal influenza vaccine in pregnant
      women, persons aged >=50 years, persons with chronic diseases, and healthcare
      personnel. We assessed adverse events following immunization (AEFI). METHODS: We
      used a multistage randomized cluster sample design to interview vaccine
      recipients. FINDINGS: Between April and May 2012, 355,902 were vaccinated. Of
      2089 persons interviewed, 261 (12.5%) reported one or more AEFI. The most
      commonly reported AEFIs were local reactions. No hospitalizations or deaths were
      reported; 16% sought medical care. Acceptance and awareness of vaccination were
      high. CONCLUSIONS: Following the introduction of seasonal influenza vaccine in
      Lao PDR, self-reported adverse events were mild.

PMID- 25598477
TI  - Wnt4 in protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides):
      identification and expression.
AB  - Wnt4 (Wingless-type MMTV integration site family member 4) has been demonstrated
      to play critical roles in ovarian development in mammals, but its function in
      fish reproduction is still unclear. In the present study, two full-length wnt4
      cDNA sequences (named wnt4a and wnt4b) were cloned from the orange-spotted
      grouper (Epinephelus coioides). Amino acid alignment analysis showed that both
      orange-spotted grouper Wnt4s proteins had the typical characteristics of the Wnt
      family. RT-PCR revealed that both wnt4a and wnt4b were highly expressed in the
      ovaries of the orange-spotted grouper. Temporal expression profiles of both wnt4
      genes during embryonic and ovarian development were examined. The expressions of
      wnt4a and wnt4b genes were first detected at the embryonic morula stage, but the
      gens showed different expression patterns. During ovarian development, high
      expression of wnt4a was observed in the ovarian lumen formation and gonium
      proliferation stage, while wnt4b exhibited strong expression in the early
      developmental stage of oocytes. Taken together, the present study indicates that
      the two wnt4 genes are involved in the regulation of ovarian development in the
      orange-spotted grouper. 

PMID- 25598478
TI  - Introduction of a new ward round approach in a cardiothoracic critical care unit.
AB  - BACKGROUND: Francis (2013) described inconsistent ward rounds and failures to
      conduct ward rounds properly as contributing factors to the poor care seen at the
      Mid Staffordshire Foundation Trust. He suggested that the absence of a nurse at
      the bedside had clear consequences for communication, ward round efficiency and
      patient safety. He recommended that nurses should be actively involved in ward
      rounds and linked this to high quality patient care. AIM: To share an experience
      of introducing a ward round checklist, a bedside nurse verbal summary and the
      development of standard operating procedure for Ward Rounds in cardiothoracic
      critical care unit to improve patient safety and care. DESIGN AND METHODS: Semi
      structured interviews of six registered nurses. A questionnaire to 69 registered
      nurses. An electronic questionnaire sent to 23 members of the MDT. An
      observational audit of seven ward rounds reviewing 69 patients. RESULTS: 97% of
      nurses agreed that verbal summarizing had improved clarity and 90% felt that it
      had improved patient care. 87% of the MDT respondents stated that they had
      noticed an improvement in the attendance of the bedside nurse at the ward round
      review. The ward round checklist reduced omissions. Communication with patients
      during ward rounds was an area which needed to be improved. CONCLUSIONS: The
      introduction of a new ward round approach and audit of its practice has enabled
      an improvement in the quality of patient care by: Giving more opportunity for the
      nurse to participate and feel part of the ward round. Reduction of omissions
      through the use of a ward round checklist. Improved clarity among the MDT by the
      use of bedside nurse verbal summarizing of the plan of care. RELEVANCE TO
      CLINICAL PRACTICE: Nurses' full participation in ward rounds is essential to
      ensure effective communication and enhance patient safety.

PMID- 25598481
TI  - From the editors.

PMID- 25598480
TI  - Hepcidin-25 vs. conventional clinical biomarkers in the diagnosis of functional
      iron deficiency.
AB  - OBJECTIVES: As hepcidin-25 is considered as a key regulator of human iron
      homoeostasis, this study aimed to compare this parameter with conventional
      biomarkers and diagnostic tools of iron deficiency (ID). METHODS: In total, 233
      hospitalised adult patients, who underwent routine blood testing for ID, were
      included. All subjects were investigated for hepcidin-25, reticulocyte
      haemoglobin content (CHr), soluble transferrin receptor (sTfR)/log ferritin ratio
      (i.e. Thomas plot), sTfR, ferritin, transferrin saturation (TSAT), C-reactive
      protein (CRP) and for complete blood cell count. Functional ID was defined as a
      CHr < 28 pg. Separate logistic regression models were calculated with all
      potential biomarkers to evaluate and compare the predictive performance with
      respect to functional ID in patients without (CRP <= 0.5 mg/dL) and with (CRP >
      0.5 mg/dL) acute-phase reaction, respectively. RESULTS: One hundred seventeen
      patients with CRP > 0.5 mg/dL showed a distinctly higher hepcidin-25 median value
      [35.60 (range: 4.27-80.03) ng/mL] as compared to 116 patients with CRP <= 0.5
      mg/dL [18.55 (range: 3.77-73.01) ng/mL]. With respect to functional ID, sTfR/log
      ferritin ratio and sTfR were of better positive predictive value (PPV) (sTfR/log
      ferritin ratio: 58.33% and 70.83%; sTfR: 60.00% and 60.00%) than when compared to
      hepcidin-25 (PPV: 37.74% and 42.86%) and ferritin (PPV: 27.54% and 46.15%) in
      both subgroups. CONCLUSIONS: The sTfR/log ferritin ratio, as well as sTfR, were
      better predictors of functional ID in patients with and without acute-phase
      reaction as compared to hepcidin-25 and ferritin.

PMID- 25598479
TI  - Superior temporal resolution of Chronos versus channelrhodopsin-2 in an
      optogenetic model of the auditory brainstem implant.
AB  - Contemporary auditory brainstem implant (ABI) performance is limited by reliance
      on electrical neurostimulation with its accompanying channel cross talk and
      current spread to non-auditory neurons. A new generation ABI based on optogenetic
      technology may ameliorate limitations fundamental to electrical stimulation. The
      most widely studied opsin is channelrhodopsin-2 (ChR2); however, its relatively
      slow kinetic properties may prevent the encoding of auditory information at high
      stimulation rates. In the present study, we compare the temporal resolution of
      light-evoked responses of ChR2 to a recently developed fast opsin, Chronos, to
      ChR2 in a murine ABI model. Viral mediated gene transfer via a posterolateral
      craniotomy was used to express Chronos or ChR2 in the cochlear nucleus (CN).
      Following a four to eight week incubation period, blue light (473 nm) was
      delivered via an optical fiber placed directly on the surface of the infected CN,
      and neural activity was recorded in the contralateral inferior colliculus (IC).
      Both ChR2 and Chronos evoked sustained responses to all stimuli, even at high
      pulse rates. In addition, optical stimulation evoked excitatory responses
      throughout the tonotopic axis of the IC. Synchrony of the light-evoked response
      to stimulus rates of 14-448 pulses/s was higher in Chronos compared to ChR2 mice
      (p < 0.05 at 56, 168, and 224 pulses/s). Our results demonstrate that Chronos has
      the ability to drive the auditory system at higher stimulation rates than ChR2
      and may be a more ideal opsin for manipulation of auditory pathways in future
      optogenetic-based neuroprostheses. This article is part of a Special Issue
      entitled "Lasker Award". 

PMID- 25598482
TI  - Is tattooing a risk factor for adolescents' criminal behavior? Empirical evidence
      from an administrative data set of juvenile detainees in Taiwan.
AB  - Juvenile crime affects not only the victims of the crime but also the
      delinquents' future. How to prevent adolescent criminal behavior has become an
      important public policy issue. This study contributes to this interesting issue
      by examining the relationship between tattooing and adolescents' criminal
      behavior. In particular, this study investigates whether or not having a
      tattoo/tattoos is connected to the incidence of various criminal activities,
      including: larceny, robbery, fraud, assault, drug use, and homicide. A unique
      sample of 973 juvenile detainees drawn from the administrative profiles in Taiwan
      and the coarsened exact matching method were utilized. Results show that compared
      to their nontattooed counterparts, tattooed juvenile detainees were significantly
      more likely to commit fraud, assault, drug abuse, and homicide by 3%, 13%, 9%,
      and 9%, respectively. In contrast, tattooing was not significantly associated
      with larceny or robbery. From a policy perspective, given the significant link
      between tattooing and criminal behavior, the presence of a tattoo in adolescents
      may serve as a valuable indicator regarding adolescents' high probability of
      committing crimes. 

PMID- 25598483
TI  - How reliable are gray matter disruptions in specific reading disability across
      multiple countries and languages? Insights from a large-scale voxel-based
      morphometry study.
AB  - The neural basis of specific reading disability (SRD) remains only partly
      understood. A dozen studies have used voxel-based morphometry (VBM) to
      investigate gray matter volume (GMV) differences between SRD and control
      children, however, recent meta-analyses suggest that few regions are consistent
      across studies. We used data collected across three countries (France, Poland,
      and Germany) with the aim of both increasing sample size (236 SRD and controls)
      to obtain a clearer picture of group differences, and of further assessing the
      consistency of the findings across languages. VBM analysis reveals a significant
      group difference in a single cluster in the left thalamus. Furthermore, we
      observe correlations between reading accuracy and GMV in the left supramarginal
      gyrus and in the left cerebellum, in controls only. Most strikingly, we fail to
      replicate all the group differences in GMV reported in previous studies, despite
      the superior statistical power. The main limitation of this study is the
      heterogeneity of the sample drawn from different countries (i.e., speaking
      languages with varying orthographic transparencies) and selected based on
      different assessment batteries. Nevertheless, analyses within each country
      support the conclusions of the cross-linguistic analysis. Explanations for the
      discrepancy between the present and previous studies may include: (1) the limited
      suitability of VBM to reveal the subtle brain disruptions underlying SRD; (2)
      insufficient correction for multiple statistical tests and flexibility in data
      analysis, and (3) publication bias in favor of positive results. Thus the study
      echoes widespread concerns about the risk of false-positive results inherent to
      small-scale VBM studies.

PMID- 25598476
TI  - HIV/AIDS and lipodystrophy: implications for clinical management in resource
      limited settings.
AB  - INTRODUCTION: Lipodystrophy is a term used to describe a metabolic complication
      of fat loss, fat gain, or a combination of fat loss and gain, which is associated
      with some antiretroviral (ARV) therapies given to HIV-infected individuals. There
      is limited research on lipodystrophy in low- and middle-income countries, despite
      accounting for more than 95% of the burden of HIV/AIDS. The objective of this
      review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related
      lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in
      resource-limited settings. METHODS: We conducted a structured literature search
      using MEDLINE electronic databases. Relevant MeSH terms were used to identify
      published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed
      syndrome in low-, low-middle- and upper-middle-income countries through 31 March
      2014. The search resulted in 5296 articles; after 1599 studies were excluded (958
      reviews, 641 non-human), 3697 studies were extracted for further review. After
      excluding studies conducted in high-income settings (n=2808), and studies that
      did not meet inclusion criteria (n = 799), 90 studies were included in this
      review. RESULTS AND DISCUSSION: Of the 90 studies included in this review, only
      six were from low-income countries and eight were from lower middle-income
      economies. These studies focused on lipodystrophy prevalence, risk factors and
      side effects of antiretroviral therapy (ART). In most studies, lipodystrophy
      developed after the first six months of therapy, particularly with the use of
      stavudine. Lipodystrophy is associated with increased risk of cardiometabolic
      complications. This is disconcerting and anticipated to increase, given the rapid
      scale-up of ART worldwide, the increasing number and lifespan of HIV-infected
      patients on long-term therapy, and the emergence of obesity and non-communicable
      diseases in settings with extensive HIV burden. CONCLUSIONS: Lipodystrophy is
      common in resource-limited settings, and has considerable implications for risk
      of metabolic diseases, quality of life and adherence. Comprehensive evidence
      based interventions are urgently needed to reduce the burden of HIV and
      lipodystrophy, and inform clinical management in resource-limited settings.

PMID- 25598484
TI  - Fast, reagentless and reliable screening of "white powders" during the
      bioterrorism hoaxes.
AB  - The classification of dry powder samples is an important step in managing the
      consequences of terrorist incidents. Fluorescence decays of these samples
      (vegetative bacteria, bacterial endospores, fungi, albumins and several flours)
      were measured with stroboscopic technique using an EasyLife LS system PTI. Three
      pulsed nanosecond LED sources, generating 280, 340 and 460nm were employed for
      samples excitation. The usefulness of a new 460nm light source for fluorescence
      measurements of dry microbial cells has been demonstrated. The principal
      component analysis (PCA) and hierarchical cluster analysis (HCA) have been used
      for classification of dry biological samples. It showed that the single
      excitation wavelength was not sufficient for differentiation of biological
      samples of diverse origin. However, merging fluorescence decays from two or three
      excitation wavelengths allowed classification of these samples. An experimental
      setup allowing the practical implementation of this method for the real time
      fluorescence decay measurement was designed. It consisted of the LED emitting
      nanosecond pulses at 280nm and two fast photomultiplier tubes (PMTs) for signal
      detection in two fluorescence bands simultaneously. The positive results of the
      dry powder samples measurements confirmed that the fluorescence decay-based
      technique could be a useful tool for fast classification of the suspected "white
      powders" performed by the first responders. 

PMID- 25598485
TI  - Calculating time since death in a mock crime case comparing a new computational
      method (ExLAC) with the ADH method.
AB  - We compared the results of calculating a minimum post-mortem interval (PMImin) in
      a mock crime case using two different methods: accumulated degree hours (ADH
      method) and a newly developed computational model called ExLAC. For the ADH
      method we further applied five reference datasets for the development time of
      Calliphora vicina (Diptera: Calliphoridae) from 5 different countries and our
      results confirmed the following: (1) Reference data for blowfly development that
      has not been sampled using a local blowfly colony should not, in most
      circumstances, be used in estimating a PMI in real cases; and (2) The new method
      ExLAC might be a potential alternative to the ADH method. 

PMID- 25598489
TI  - Correction: Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique
      class of disulfide-containing antibiotics.

PMID- 25598488
TI  - Crowding increases salivary cortisol but not self-directed behavior in captive
      baboons.
AB  - Reduced space can lead to crowding in social animals. Crowding increases the risk
      of agonistic interactions that, in turn, may require additional physiological
      defensive coping mechanisms affecting health. To determine the stress induced
      from increased social density in a group of nineteen baboons living in an
      indoor/outdoor enclosure, saliva cortisol levels and rates of anxiety-related
      behavior were analyzed across two unique crowding episodes. Initially, mean
      salivary cortisol levels when animals were restricted to their indoor quarters
      were compared to those when they also had access to their larger outdoor
      enclosure. Then, mean cortisol levels were compared before, during, and after two
      distinct crowding periods of long and short duration. Crowding resulted in
      significantly elevated cortisol during crowding periods compared to non-crowded
      periods. Cortisol levels returned to baseline following two crowding episodes
      contrasting in their length and ambient climate conditions. These cortisol
      elevations indicate greater metabolic costs of maintaining homeostasis under
      social stress resulting from reduced space. Self-directed behavior, conversely,
      was not reliably elevated during crowding. Results suggest that the potential for
      negative social interactions, and/or the uncertainty associated with social
      threat can cause physiological stress responses detected by salivary cortisol.
      Self-directed behavioral measures of stress may constitute inadequate indicators
      of social stress in colony-housed monkeys or represent subjective emotional
      arousal unrelated to hypothalamic-pituitary adrenal axis activation.

PMID- 25598486
TI  - Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing
      on mitochondria.
AB  - Oxidative stress-induced lipid peroxidation has been associated with human
      physiology and diseases including cancer. Overwhelming data suggest that reactive
      lipid mediators generated from this process, such as 4-hydroxynonenal (4-HNE),
      are biomarkers for oxidative stress and important players for mediating a number
      of signaling pathways. The biological effects of 4-HNE are primarily due to
      covalent modification of important biomolecules including proteins, DNA, and
      phospholipids containing amino group. In this review, we summarize recent
      progress on the role of 4-HNE in pathogenesis of cancer and focus on the
      involvement of mitochondria: generation of 4-HNE from oxidation of mitochondria
      specific phospholipid cardiolipin; covalent modification of mitochondrial
      proteins, lipids, and DNA; potential therapeutic strategies for targeting
      mitochondrial ROS generation, lipid peroxidation, and 4-HNE. 

PMID- 25598487
TI  - Synthesis of 2-aryl-3-(2-cyanoethyl)aziridines and their chemical and enzymatic
      hydrolysis towards gamma-lactams and gamma-lactones.
AB  - Trans- and cis-2-aryl-3-(2-cyanoethyl)aziridines, prepared via alkylation of the
      corresponding 2-aryl-3-(tosyloxymethyl)aziridines with the sodium salt of
      trimethylsilylacetonitrile, were transformed into variable mixtures of 4
      [aryl(alkylamino)methyl]butyrolactones and 5-[aryl(hydroxy)methyl]pyrrolidin-2
      ones via KOH-mediated hydrolysis of the cyano group, followed by ring expansion.
      In addition, next to this chemical approach, enzymatic hydrolysis of the former
      aziridinyl nitriles by means of a nitrilase was performed as well, interestingly
      providing a selective route towards the above-mentioned functionalized gamma
      lactams. 

PMID- 25598490
TI  - Quantum ratchet in two-dimensional semiconductors with Rashba spin-orbit
      interaction.
AB  - Ratchet is a device that produces direct current of particles when driven by an
      unbiased force. We demonstrate a simple scattering quantum ratchet based on an
      asymmetrical quantum tunneling effect in two-dimensional electron gas with Rashba
      spin-orbit interaction (R2DEG). We consider the tunneling of electrons across a
      square potential barrier sandwiched by interface scattering potentials of unequal
      strengths on its either sides. It is found that while the intra-spin tunneling
      probabilities remain unchanged, the inter-spin-subband tunneling probabilities of
      electrons crossing the barrier in one direction is unequal to that of the
      opposite direction. Hence, when the system is driven by an unbiased periodic
      force, a directional flow of electron current is generated. The scattering
      quantum ratchet in R2DEG is conceptually simple and is capable of converting a.c.
      driving force into a rectified current without the need of additional symmetry
      breaking mechanism or external magnetic field. 

PMID- 25598491
TI  - Recurrent encephaloclastic cyst induced by intraventricular topotecan.
AB  - OBJECTIVE: To report two rare cases of encephaloclastic cyst induced by
      intraventricular topotecan. To share our experience in diagnosing and treating
      this rare disease. BACKGROUND: Ommaya reservoirs provide fast access and reliable
      drug delivery to cerebral spinal fluid. They are routinely utilized for the
      administration of intrathecal chemotherapy accounting for greater than 80% of
      cases for which they are used. Complications of Ommaya reservoir placement and
      its use consist of infectious and other late noninfectious causes.
      Encephaloclastic cysts provoked by intraventricular chemotherapy are very
      uncommon. The pathogenesis may result from alterations in CSF pulsations with
      retrograde flow of intraventricular chemotherapy into the brain parenchyma and
      subsequent development of a local chemical encephalopathy. It has been previously
      reported with methotrexate use but never with topotecan administration. METHODS:
      We report two rare cases of encephaloclastic cyst with intraventricular topotecan
      use. The patients were diagnosed and treated at The University of Texas MD
      Anderson Cancer Center. They consented to the publication of their laboratory
      results and imaging studies for educational purposes. RESULT: The patients
      presented with metastatic cancers (breast/lung) complicated by leptomeningeal
      disease. Ommaya reservoirs were placed in both cases and patients were initiated
      on intraventricular topotecan at 0.4 mg twice weekly. After approximately 12
      intraventricular treatments, both patients developed confusion, seizures and
      headaches. MRI of the brain demonstrated cystic dilatation of the brain
      parenchyma around the catheter that connects to the reservoir dome and delivers
      the drug to the intraventricular space. The catheter was surrounded by vasogenic
      edema. Catheters were removed and analyzed and were found to be intact. CSF
      analyses showed no evidence of infection or malignancy. Intraventricular
      topotecan was discontinued and both patients demonstrated sustained clinical and
      radiological responses. CONCLUSION: These cases highlight an atypical
      complication of intraventricular use of topotecan with successful management.

PMID- 25598492
TI  - Role of interferon-beta in Mycobacterium avium subspecies paratuberculosis
      antibody response in Sardinian MS patients.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is associated
      with MS in Sardinia. Because anti-MAP antibodies (Abs) were more frequent in
      interferon-beta treated patients, we hypothesize that interferon-beta could
      interact with the immune system. METHODS: Anti-MAP Abs were searched in the blood
      of 89 patients before commencing interferon-beta and after at least six months.
      RESULTS: Anti-MAP Abs were detected before and during treatment in 18.7% and
      34.7% of patients, respectively. Twenty-three (20.5%) patients became positive
      during therapy, and 5 (4.4%) patients became negative (p=0.001). CONCLUSIONS: The
      study supports the hypothesis that interferon-beta could interact with the immune
      system, enhancing the immunological response against MAP.

PMID- 25598493
TI  - PPIs as possible risk factor for copper deficiency myelopathy.

PMID- 25598494
TI  - Activation of the manganese(I) tricarbonyl core by selective variation of
      bidentate ligands (L,L'-Bid = N,N' and N,O donor atom sets) in fac-[Mn(CO)3(L,L'
      Bid)(CH3OH)](n) complexes.
AB  - A range of fac-[Mn(CO)3(L,L'-Bid)(H2O)](n) (L,L'-Bid = neutral or monoanionic
      bidentate ligands with varied L,L' donor atoms, N,N' and N,O, 1,10
      phenanthroline, 2,2'-bipyridine, 2-picolinate, 2,4-quinolinate; n = 0, +1) has
      been synthesized and the methanol substitution has been investigated for the
      first time. The complexes were characterized by UV/vis, IR and NMR spectroscopy
      and X-ray crystallographic studies of the compounds fac
      [Mn(CO)3(Bipy)(H2O)][CF3SO3] () and fac-[Mn(CO)3(Phen)(H2O)][CF3SO3] () are
      reported. A two order-of-magnitude of activation for the methanol substitution is
      induced as manifested by the second order rate constants with (N,N'-Bid) < (N,O
      Bid). Forward and reverse rate and stability constants from slow and stopped-flow
      UV/vis measurements (k1, M(-1) s(-1); k-1, s(-1); K1, M(-1)) for pyridine as
      entering nucleophile are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (2.39 +/- 5) *
      10(-3), (1.5 +/- 0.3) * 10(-5), 159 +/- 32; fac-[Mn(CO)3(2,4-QuinH)(CH3OH)] (4.5
      +/- 0.2), (4 +/- 1) * 10(-2), 113 +/- 29. Activation parameters (DeltaH, kJ mol(
      1); DeltaS, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as
      indicated are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (bromide ions) 66.7 +/-
      0.6, -27 +/- 2; (pyridine) 80 +/- 3, -25 +/- 11; fac-[Mn(CO)3(Pico)(CH3OH)]
      (bromide ions) 68 +/- 2, -24 +/- 5. A dissociative interchange mechanism is
      proposed. 

PMID- 25598496
TI  - Stable bis(trifluoromethyl)nickel(III) complexes.
AB  - Organometallic Ni(III) intermediates have been proposed in several Nickel
      catalyzed cross-coupling reactions, yet no isolated bis(hydrocarbyl)Ni(III)
      complexes have been reported to date. Herein we report the synthesis and detailed
      characterization of stable organometallic Ni(III) complexes that contain two
      trifluoromethyl ligands and are supported by tetradentate N-donor ligands (R)N4
      (R = Me or tBu). Interestingly, the corresponding Ni(II) precursors undergo
      facile oxidation, including aerobic oxidation, to generate uncommonly stable
      organometallic Ni(III) complexes that exhibit limited reactivity.

PMID- 25598497
TI  - Involvement of loops 2 and 3 of alpha-sarcin on its ribotoxic activity.
AB  - Ribotoxins are a family of fungal ribosome-inactivating proteins displaying
      highly specific ribonucleolytic activity against the sarcin/ricin loop (SRL) of
      the larger rRNA, with alpha-sarcin as its best-characterized member. Their
      toxicity arises from the combination of this activity with their ability to cross
      cell membranes. The involvement of alpha-sarcin's loops 2 and 3 in SRL and
      ribosomal proteins recognition, as well as in the ribotoxin-lipid interactions
      involving cell penetration, has been suggested some time ago. In the work
      presented now different mutants have been prepared in order to study the role of
      these loops in their ribonucleolytic and lipid-interacting properties. The
      results obtained confirm that loop 3 residues Lys 111, 112, and 114 are key
      actors of the specific recognition of the SRL. In addition, it is also shown that
      Lys 114 and Tyr 48 conform a network of interactions which is essential for the
      catalysis. Lipid-interaction studies show that this Lys-rich region is indeed
      involved in the phospholipids recognition needed to cross cell membranes. Loop 2
      is shown to be responsible for the conformational change which exposes the region
      establishing hydrophobic interactions with the membrane inner leaflets and eases
      penetration of ribotoxins target cells. 

PMID- 25598498
TI  - Neuromuscular effects of venoms and crotoxin-like proteins from Crotalus durissus
      ruruima and Crotalus durissus cumanensis.
AB  - A myographic study was performed to compare the neuromuscular effects of venoms
      and crotoxin-like proteins from Crotalus durissus ruruima and Crotalus durissus
      cumanensis in mice phrenic-diaphragm preparation. It was concluded that both
      venoms present neurotoxic activity as a consequence of their crotoxin content.
      Furthermore, crotoxin from C.d. cumanensis is more potent than that from C.d.
      ruruima venom. At the concentration range in which both venoms express neurotoxic
      activity, only C.d. cumanensis venom also manifest a direct myotoxic effect that
      probably involves the synergic participation of other components than crotoxin. 

PMID- 25598499
TI  - Mathematical modelling of the diurnal regulation of the MEP pathway in
      Arabidopsis.
AB  - Isoprenoid molecules are essential elements of plant metabolism. Many important
      plant isoprenoids, such as chlorophylls, carotenoids, tocopherols, prenylated
      quinones and hormones are synthesised in chloroplasts via the 2-C-methyl-d
      erythritol 4-phosphate (MEP) pathway. Here we develop a mathematical model of
      diurnal regulation of the MEP pathway in Arabidopsis thaliana. We used both
      experimental and theoretical approaches to integrate mechanisms potentially
      involved in the diurnal control of the pathway. Our data show that flux through
      the MEP pathway is accelerated in light due to the photosynthesis-dependent
      supply of metabolic substrates of the pathway and the transcriptional regulation
      of key biosynthetic genes by the circadian clock. We also demonstrate that
      feedback regulation of both the activity and the abundance of the first enzyme of
      the MEP pathway (1-deoxy-D-xylulose 5-phosphate synthase, DXS) by pathway
      products stabilizes the flux against changes in substrate supply and adjusts the
      flux according to product demand under normal growth conditions. These data
      illustrate the central relevance of photosynthesis, the circadian clock and
      feedback control of DXS for the diurnal regulation of the MEP pathway.

PMID- 25598495
TI  - Increased atrial arrhythmia susceptibility induced by intense endurance exercise
      in mice requires TNFalpha.
AB  - Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for
      unknown reasons, is linked to intense endurance exercise. Our studies reveal that
      6 weeks of swimming or treadmill exercise improves heart pump function and
      reduces heart-rates. Exercise also increases vulnerability to AF in association
      with inflammation, fibrosis, increased vagal tone, slowed conduction velocity,
      prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII
      dependent S2814) in the atria, without corresponding alterations in the
      ventricles. Microarray results suggest the involvement of the inflammatory
      cytokine, TNFalpha, in exercised-induced atrial remodelling. Accordingly,
      exercise induces TNFalpha-dependent activation of both NFkappaB and p38MAPK,
      while TNFalpha inhibition (with etanercept), TNFalpha gene ablation, or p38
      inhibition, prevents atrial structural remodelling and AF vulnerability in
      response to exercise, without affecting the beneficial physiological changes. Our
      results identify TNFalpha as a key factor in the pathology of intense exercise
      induced AF. 

PMID- 25598500
TI  - Melatonin modulated autophagy and Nrf2 signaling pathways in mice with colitis
      associated colon carcinogenesis.
AB  - Colon carcinogenesis is long known to be associated with ulcerative colitis (UC),
      a chronic gastrointestinal disorder. Various pre-clinical and clinical studies
      have shown that melatonin (MEL) has beneficial effects in cancer. However,
      elucidation of the detailed molecular mechanisms involved in MEL-mediated
      protection against the colon carcinogenesis deserves further investigation. The
      present study was aimed at deciphering the effect of MEL on autophagy and Nrf2
      signaling pathways in a mouse model of colitis-associated colon carcinogenesis
      (CACC). For the induction of CACC, male Swiss Albino mice were administered a
      single ip injection of 20 mg 1, 2-dimethylhydrazine dihydrochloride (DMH)/kg bw,
      followed by 3 cycles of 3% w/v dextran sulfate sodium (DSS) in drinking water
      treatment initiated 1 wk after DMH injection. One week after the initiation of
      DSS treatment, MEL was administered at the dose of 1 mg/kg, bw, po for 8 and 18
      wk. Mice were sacrificed at 10 and 20 wk after DMH injection. MEL treatment
      decreased the progression of CACC by down regulating the process of autophagy as
      revealed by the expression pattern of various autophagy markers such as Beclin-1,
      LC3B-II/LC3B-I ratio and p62. These findings were accompanied with the increased
      expression of Nrf2 and the associated antioxidant enzymes, NAD(P)H: quinone
      oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in the colon of mice with
      CACC. MEL intervention reduced autophagy by ameliorating inflammation and
      oxidative stress in the colon of mice with CACC. We conclude that MEL treatment
      attenuates the progression of CACC in mice by modulating autophagy and Nrf2
      signaling pathways.

PMID- 25598501
TI  - Regional brain [(11)C]carfentanil binding following tobacco smoking.
AB  - OBJECTIVE: To determine if overnight tobacco abstinent carriers of the AG or GG
      (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G
      polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco
      smoking. METHODS: Twenty healthy American male smokers who abstained from tobacco
      overnight were genotyped and completed positron emission tomography (PET) scans
      with the mu opioid receptor agonist, [(11)C]carfentanil. They smoked deniconized
      (denic) and average nicotine (avnic) cigarettes during the PET scans. RESULTS:
      Smoking avnic cigarette decreased the binding potential (BPND) of
      [(11)C]carfentanil in the right medial prefrontal cortex (mPfc; 6, 56, 18), left
      anterior medial prefrontal cortex (amPfc; -2, 46, 44), right ventral striatum
      (vStr; 16, 3, -10), left insula (Ins; -42, 10, -12), right hippocampus (Hippo;
      18, -6, -14) and left cerebellum (Cbl; -10, -88, -34), and increased the BPND in
      left amygdala (Amy; -20, 0, -22), left putamen (Put; -22, 10, -6) and left
      nucleus accumbens (NAcc; -10, 12, -8). In the AA allele carriers, avnic cigarette
      smoking significantly changed the BPND compared to after denic smoking in most
      brain areas listed above. However in the *G carriers the significant BPND changes
      were confirmed in only amPfc and vStr. Free mu opioid receptor availability was
      significantly less in the *G than the AA carriers in the Amy and NAcc.
      CONCLUSION: The present study demonstrates that BPND changes induced by avnic
      smoking in OPRM1 *G carriers were blunted compared to the AA carriers. Also *G
      smokers had less free mu opioid receptor availability in Amy and NAcc.

PMID- 25598503
TI  - The transverse parietooccipital transposition flap for the closure of extensive
      frontoparietal scalp defects.

PMID- 25598504
TI  - Association between genetic polymorphisms in DNA mismatch repair-related genes
      with risk and prognosis of head and neck squamous cell carcinoma.
AB  - We examined the influence of MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A and
      EXO1 c.1765G>A polymorphisms, involved in DNA mismatch repair (MMR), on head and
      neck (HN) squamous cell carcinoma (SCC) risk and prognosis. Aiming to identify
      genotypes, DNA from 450 HNSCC patients and 450 controls was analyzed by PCR-RFLP
      or real time PCR. MSH2 GG plus MSH3 GG (31.7% vs. 18.7%, p = 0.003) genotypes
      were higher in laryngeal SCC (LSCC) patients than in controls. Carriers of the
      respective combined genotype were under a 3.69 (95% CI: 1.54-8.81)-fold increased
      risk of LSCC. Interactions of tobacco and tobacco plus all the above-mentioned
      polymorphisms on HNSCC and LSCC risk were also evident in study (p = 0.001). At
      60 months of follow-up, relapse-free survival (RFS) was shorter in patients with
      EXO1 GG genotype (54.8% vs. 61.1%, p = 0.03) and overall survival (OS) was
      shorter in patients with MSH3 GG genotype (42.8% vs. 52.5%, p = 0.02) compared to
      those with other genotypes, respectively. After multivariate Cox analysis,
      patients with EXO1 GG and MSH3 GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03
      2.20, p = 0.03) and OS (HR: 1.59, 95% CI: 1.19-2.13, P = 0.002) than those with
      the remaining genotypes, respectively. Our data present, for the first time,
      evidence that inherited MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, and
      EXO1 c.1765G>A abnormalities of DNA MMR pathway are important determinants of
      HNSCC, particularly among smokers, and predictors of patient outcomes.

PMID- 25598506
TI  - Simultaneous determination of multiclass preservatives including isothiazolinones
      and benzophenone-type UV filters in household and personal care products by
      micellar electrokinetic chromatography.
AB  - In this work, a simple and reliable micellar electrokinetic chromatography method
      for the separation and quantification of 14 preservatives, including
      isothiazolinones, and two benzophenone-type UV filters in household, cosmetic and
      personal care products was developed. The selected priority compounds are widely
      used as ingredients in many personal care products, and are included in the
      European Regulation concerning cosmetic products. The electrophoretic separation
      parameters were optimized by means of a modified chromatographic response
      function in combination with an experimental design, namely a central composite
      design. After optimization of experimental conditions, the BGE selected for the
      separation of the targets consisted of 60 mM SDS, 18 mM sodium tetraborate, pH
      9.4 and 10% v/v methanol. The MEKC method was checked in terms of linearity, LODs
      and quantification, repeatability, intermediate precision, and accuracy,
      providing appropriate values (i.e. R(2) >= 0.992, repeatability RSD values ?9%,
      and accuracy 90-115%). Applicability of the validated method was successfully
      assessed by quantifying preservatives and UV filters in commercial consumer
      products.

PMID- 25598502
TI  - Associations between DNA methylation and schizophrenia-related intermediate
      phenotypes - a gene set enrichment analysis.
AB  - Multiple genetic approaches have identified microRNAs as key effectors in
      psychiatric disorders as they post-transcriptionally regulate expression of
      thousands of target genes. However, their role in specific psychiatric diseases
      remains poorly understood. In addition, epigenetic mechanisms such as DNA
      methylation, which affect the expression of both microRNAs and coding genes, are
      critical for our understanding of molecular mechanisms in schizophrenia. Using
      clinical, imaging, genetic, and epigenetic data of 103 patients with
      schizophrenia and 111 healthy controls of the Mind Clinical Imaging Consortium
      (MCIC) study of schizophrenia, we conducted gene set enrichment analysis to
      identify markers for schizophrenia-associated intermediate phenotypes. Genes were
      ranked based on the correlation between DNA methylation patterns and each
      phenotype, and then searched for enrichment in 221 predicted microRNA target gene
      sets. We found the predicted hsa-miR-219a-5p target gene set to be significantly
      enriched for genes (EPHA4, PKNOX1, ESR1, among others) whose methylation status
      is correlated with hippocampal volume independent of disease status. Our results
      were strengthened by significant associations between hsa-miR-219a-5p target gene
      methylation patterns and hippocampus-related neuropsychological variables. IPA
      pathway analysis of the respective predicted hsa-miR-219a-5p target genes
      revealed associated network functions in behavior and developmental disorders.
      Altered methylation patterns of predicted hsa-miR-219a-5p target genes are
      associated with a structural aberration of the brain that has been proposed as a
      possible biomarker for schizophrenia. The (dys)regulation of microRNA target
      genes by epigenetic mechanisms may confer additional risk for developing
      psychiatric symptoms. Further study is needed to understand possible interactions
      between microRNAs and epigenetic changes and their impact on risk for brain-based
      disorders such as schizophrenia. 

PMID- 25598507
TI  - Progressive glucose stimulation of islet beta cells reveals a transition from
      segregated to integrated modular functional connectivity patterns.
AB  - Collective beta cell activity in islets of Langerhans is critical for the supply
      of insulin within an organism. Even though individual beta cells are
      intrinsically heterogeneous, the presence of intercellular coupling mechanisms
      ensures coordinated activity and a well-regulated exocytosis of insulin. In order
      to get a detailed insight into the functional organization of the syncytium, we
      applied advanced analytical tools from the realm of complex network theory to
      uncover the functional connectivity pattern among cells composing the intact
      islet. The procedure is based on the determination of correlations between long
      temporal traces obtained from confocal functional multicellular calcium imaging
      of beta cells stimulated in a stepwise manner with a range of physiological
      glucose concentrations. Our results revealed that the extracted connectivity
      networks are sparse for low glucose concentrations, whereas for higher
      stimulatory levels they become more densely connected. Most importantly, for all
      ranges of glucose concentration beta cells within the islets form locally
      clustered functional sub-compartments, thereby indicating that their collective
      activity profiles exhibit a modular nature. Moreover, we show that the observed
      non-linear functional relationship between different network metrics and glucose
      concentration represents a well-balanced setup that parallels physiological
      insulin release. 

PMID- 25598505
TI  - A holistic approach to targeting disease with polymeric nanoparticles.
AB  - The primary goal of nanomedicine is to improve clinical outcomes. To this end,
      targeted nanoparticles are engineered to reduce non-productive distribution while
      improving diagnostic and therapeutic efficacy. Paradoxically, as this field has
      matured, the notion of targeting has been minimized to the concept of increasing
      the affinity of a nanoparticle for its target. This Opinion article outlines a
      holistic view of nanoparticle targeting, in which the route of administration,
      molecular characteristics and temporal control of the nanoparticles are potential
      design variables that must be considered simultaneously. This comprehensive
      vision for nanoparticle targeting will facilitate the integration of
      nanomedicines into clinical practice. 

PMID- 25598509
TI  - Metabolism in embryonic and cancer stemness.
AB  - Cells constantly adjust their metabolic state in response to extracellular
      signals and nutrient availability to meet their demand for energy and building
      blocks. Recently, there has been significant research into the metabolic aspects
      of embryonic stem cells/pluripotent stem cells (ESCs/PSCs) and cancer stem cells
      (CSCs), which has revealed the unique metabolic status of different stem cell
      lineages. While ESCs and CSCs were largely thought to harbor similar metabolic
      states, recent evidence demonstrates that their metabolic dependency is
      distinctly different. The glucose metabolism of ESCs largely depends on
      glycolysis, including a one-carbon pathway during differentiation. While
      proliferating cancer cells share the glycolytic phenotype of ESCs, the
      mitochondria-centric oxidative phosphorylation constitutes an important metabolic
      circuit of CSCs under metabolic stress, indicating the dynamic nature of
      metabolic plasticity. In this review, we catalogued metabolic signatures of
      cellular "stemness" to provide insights into the therapeutic potential of ESCs
      and CSCs.

PMID- 25598510
TI  - Clinical, histopathological and immunohistochemical study of oral squamous
      papillomas.
AB  - OBJECTIVE: The aim of this study was to analyze the clinicopathological and
      immunohistochemical features of oral papillomas. MATERIALS AND METHODS: Biopsies
      of oral papillomas analyzed in the laboratory between 1996-2012 were extracted
      from the database and used to conduct this retrospective review. The following
      clinical data were extracted: sex, age, location, clinical appearance, time of
      evolution, recurrence and first clinical diagnosis. Immunohistochemical analysis
      for Human Papillomavirus (HPV)and histological evaluation of the lesions were
      performed. RESULTS: A total of 205 papillomas were identified in 197 patients
      (?=110, ? = 87; mean age = 48.4 +/- 17.9 years).The majority of the lesions (n =
      47) occurred on the soft palate (23%). The border of the tongue was the second
      most common site (n = 20, 9.8%). Lesions were more common in males than in
      females (ratio = 1.26:1). Statistical analysis did not show any correlation
      between the assessed variables. Clinically, papillomas were predominantly
      described by the practitioners as small nodules, with a papillary surface (98.1%)
      and pedunculated attachment(83.1%). Data supported a low recurrence (2.0%) and
      multiplicity (2.0%). Evolution time varied from a few weeks to several years.
      Most frequent misdiagnosis was condyloma. Immunohistochemistry rarely showed HPV
      presence (9.3%). Microscopically, lesions were very often keratinized (93.2%) and
      showed chronic inflammatory cells (68.8%). CONCLUSIONS: In this series papillomas
      showed a slight male predilection and occurred mostly in the sixth decade of
      life. Histologically, they were usually keratotic and exhibited variable
      inflammation. HPV virus was rarely detected by immunohistochemistry. No
      statistical correlation could be established between clinicopathological
      features.

PMID- 25598508
TI  - Regulation of MU and delta opioid receptor functions: involvement of cyclin
      dependent kinase 5.
AB  - BACKGROUND AND PURPOSE: Phosphorylation of delta opioid receptors (DOP receptors)
      by cyclin-dependent kinase 5 (CDK5) was shown to regulate the trafficking of this
      receptor. Therefore, we aimed to determine the role of CDK5 in regulating DOP
      receptors in rats treated with morphine or with complete Freund's adjuvant (CFA).
      As MU (MOP) and DOP receptors are known to be co-regulated, we also sought to
      determine if CDK5-mediated regulation of DOP receptors also affects MOP receptor
      functions. EXPERIMENTAL APPROACH: The role of CDK5 in regulating opioid receptors
      in CFA- and morphine-treated rats was studied using roscovitine as a CDK
      inhibitor and a cell-penetrant peptide mimicking the second intracellular loop of
      DOP receptors (C11-DOPri2). Opioid receptor functions were assessed in vivo in a
      series of behavioural experiments and correlated by measuring ERK1/2 activity in
      dorsal root ganglia homogenates. KEY RESULTS: Chronic roscovitine treatment
      reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt
      II) in morphine- and CFA-treated rats respectively. Repeated administrations of
      C11-DOPri2 also robustly decreased Dlt II-induced analgesia. Interestingly, DAMGO
      induced analgesia was significantly increased by roscovitine and C11-DOPri2.
      Concomitantly, in roscovitine-treated rats the Dlt II-induced ERK1/2 activation
      was decreased, whereas the DAMGO-induced ERK1/2 activation was increased. An
      acute roscovitine treatment had no effect on Dlt II- or DAMGO-induced analgesia.
      CONCLUSIONS AND IMPLICATIONS: Together, our results demonstrate that CDK5 is a
      key player in the regulation of DOP receptors in morphine- and CFA-treated rats
      and that the regulation of DOP receptors by CDK5 is sufficient to modulate MOP
      receptor functions through an indirect process.

PMID- 25598511
TI  - Composition of nonanthocyanin polyphenols in alcoholic-fermented strawberry
      products using LC-MS (QTRAP), high-resolution MS (UHPLC-Orbitrap-MS), LC-DAD, and
      antioxidant activity.
AB  - In this study, the nonanthocyanin (poly)phenolic profile of an alcoholic
      fermented strawberry beverage was characterized. High-performance liquid
      chromatography coupled with a triple-quadropole mass spectrometer and ultra-high
      performance liquid chromatography coupled with a linear trap quadropole and an
      Orbitrap mass analyzer was used to identify nonanthocyanin phenolic compounds.
      Sixty-six compounds were identified, and 13 of these were identified for the
      first time in strawberry or its derived alcoholic fermented beverage:
      protocatechuic acid-4-O-beta-hexoside, brevifolin carboxylic acid, ferulic acid
      glucuronide, dimer caffeic acid-O-hexoside, luteolin-3'-O-xyloside, isorhamnetin
      3-O-glucoside, taxifolin-O-glucoside, (+)-aromadendrin rhamnoside, eriodictyol-7
      O-glucoside, (+)-taxifolin, (+)-aromadendrin, eriodictyol, and homovanillic acid.
      The alcoholic fermentation process produced significant increases in certain
      compounds, such as homovanillic acid and p-hydroxybenzoic acid, while a
      significant decrease in galloyl bis-HHDP-glucose was observed. Linear
      discriminant analysis correctly classified samples initial, final, and
      pasteurized, which led to the conclusion that alcoholic fermentation induces
      significant changes in composition, mainly in relation to the 19 compounds
      represented in the tables of this work. 

PMID- 25598512
TI  - Management of recurrent stress urinary incontinence after burch and sling
      procedures.
AB  - AIMS: To examine treatment options selected for recurrent stress urinary
      incontinence (rSUI) in follow-up after Burch, autologous fascial and synthetic
      midurethral sling (MUS) procedures. METHODS: We performed a secondary analysis of
      the SISTER and ToMUS trials of participants who underwent primary stress urinary
      incontinence (SUI) treatment (without prior SUI surgery or concomitant
      procedures). Using Kaplan-Meier analysis, retreatment-free survival rates by
      initial surgical procedure were compared. Mean MESA (Medical Epidemiologic and
      Social Aspects of Aging) stress index was also compared between those retreated
      for rSUI compared to those not retreated. RESULTS: Half of the women in the
      SISTEr trial met inclusion criteria for this analysis (329/655, 174 Burch and 155
      fascial sling), as did 444/597 (74%) of subjects in ToMUS (221 transobturator
      midurethral sling (TMUS), and 223 retropubic midurethral sling (RMUS). Types of
      surgical retreatment included autologous fascial sling (19), synthetic sling (1),
      and bulking agent (18). Five-year retreatment free survival rates (and standard
      errors) were 87% (3%), 96% (2%), 97% (1%), and 99% (0.7%) for Burch, autologous
      fascial sling, TMUS, and RMUS groups respectively (P < 0.0001). For all index
      surgery groups, the mean MESA stress index at last visit prior to retreatment for
      those retreated (n = 23) was significantly higher than mean MESA stress index at
      last visit for those not retreated (n = 645) (P < 0.0001). CONCLUSION: In these
      cohorts, 6% of women after standard anti-incontinence procedures were retreated
      within 5 years, mostly with injection therapy or autologous fascial sling. Not
      all women with rSUI chose surgical retreatment.

PMID- 25598513
TI  - Membrane proteins - do we catch up with the breathless pace of soluble protein
      structural biology?

PMID- 25598514
TI  - Single-bacterium nanomechanics in biomedicine: unravelling the dynamics of
      bacterial cells.
AB  - The use of the atomic force microscope (AFM) in microbiology has progressed
      significantly throughout the years since its first application as a high
      resolution imaging instrument. Modern AFM setups are capable of characterizing
      the nanomechanical behaviour of bacterial cells at both the cellular and
      molecular levels, where elastic properties and adhesion forces of single
      bacterium cells can be examined under different experimental conditions.
      Considering that bacterial and biofilm-mediated infections continue to challenge
      the biomedical field, it is important to understand the biophysical events
      leading towards bacterial adhesion and colonization on both biological and non
      biological substrates. The purpose of this review is to present the latest
      findings concerning the field of single-bacterium nanomechanics, and discuss
      future trends and applications of nanoindentation and single-cell force
      spectroscopy techniques in biomedicine. 

PMID- 25598515
TI  - The activity of paraoxonase type 1 (PON-1) in boar seminal plasma and its
      relationship with sperm quality, functionality, and in vivo fertility.
AB  - Paraoxonase 1 (PON-1) is a hydrolytic enzyme present in body fluids, capable of
      protecting cells against oxidative stress. The hypothesis was hereby to test that
      PON-1, present in seminal plasma (SP), acts protecting boar spermatozoa when
      showing a reasonable high activity in the ejaculate. SP-PON-1 activity differed
      (p < 0.001) among boars (from 0.10 to 0.29 IU/mL). Intra-boar variability was
      also observed (p < 0.05), but only in two of the 15 boars. SP-PON-1 activity
      differed among ejaculate portions, showing the spermatozoa-peak portion of
      spermatozoa-rich ejaculate fraction the highest levels (0.35 +/- 0.03 IU/mL,
      ranging from 0.12 to 0.69) and the post-sperm ejaculate fraction the lowest
      levels (0.12 +/- 0.01 IU/mL, ranging from 0.03 to 0.21). SP-PON-1 activity was
      positively correlated with the percentage of spermatozoa with rapid and
      progressive movement (p < 0.01) and negatively correlated with the generation of
      intracellular reactive oxygen species (p < 0.01) in semen samples after 72 h of
      liquid storage. SP-PON-1 activity was highest (p < 0.01) in boars with highest
      farrowing rates. In conclusion, SP-PON-1 activity differed among boars and
      ejaculate fractions/portions. SP-PON-1 activity was positively correlated with
      sperm quality and functionality of liquid-stored semen samples and it evidenced a
      positive association with in vivo fertility.

PMID- 25598516
TI  - Regulatory effects on central carbon metabolism from poly-3-hydroxybutryate
      synthesis.
AB  - Poly-3-hydroxybutyrate (PHB) synthesis in Escherichia coli elicits regulatory
      responses that affect product yield and productivity. We used controlled, steady
      state cultures (chemostats) of a genetically stable strain to determine growth
      independent metabolic flux regulation. We measured flux and steady-state
      intracellular metabolite concentrations across different dilution rates (0.05,
      0.15, 0.3h(-1)), limitations (glucose, gluconate and nitrogen), and operon copy
      counts of the PHB pathway (0, 6, 17, and 29). As PHB flux increases, specific
      substrate consumption and lactate secretion increase while formate and acetate
      secretion decreases in N-limited, glucose-fed conditions. To understand the
      regulatory mechanisms that resulted in these macroscopic changes, we used a flux
      balance analysis model to analyze intracellular redox conditions. Our model shows
      that under N-limited conditions, synthesis of PHB creates excess reducing
      equivalents. Cells, under these conditions, secrete more reduced metabolites in
      order to recycle reducing equivalents. By switching to a more oxidized substrate
      (gluconate) that decreased excess reducing equivalents, PHB flux yield increased
      1.6 fold compared to glucose-fed fermentations. High flux of PHB (~1.2 mmol/g
      DCWh) was maintained under these steady-state, oxidized conditions. These results
      imply redox imbalance is a driving force in industrial production of PHB, and
      substrates that are more oxidized than glucose can increase productivity.

PMID- 25598518
TI  - Expert testimony: implications for life care planning.

PMID- 25598519
TI  - The prevalence of Vitamin D deficiency is higher in adult survivors of childhood
      cancer.
AB  - BACKGROUND: It is unclear whether the rate of vitamin D deficiency in paediatric
      cancer survivors is higher than in the background population, and whether this is
      of pathological significance. PATIENTS AND METHODS: 25OHD was measured in a
      previously studied group of 208 survivors (n = 108 paediatric 5-17 years, n = 99
      adults 18-39 years) and compared with paediatric (5-17 years; n = 132) and adult
      controls (25-35 years; n = 1393 from the AusDiab cohort) adjusted for age and
      gender. Relationships with treatment factors (irradiation, bone marrow
      transplantation and intensity of treatment) along with overweight/obesity
      (defined by BMI), abdominal adiposity (waist:height ratio >0.5) and
      hyperinsulinism or abnormal glucose tolerance (HI/aGT) were sought. RESULTS:
      25OHD concentrations were similar in paediatric survivors compared with controls
      (64.3 +/- 21.6 nmol/l vs 66.3 +/- 22.8 nmol/l), with no effect of age or gender.
      Adjusted for gender, rates of 25OHD deficiency (<50 nmol/l) were higher in adult
      survivors compared with AusDiab controls (42.4% vs 20.8%; P < 0.001). Apart from
      time since diagnosis (P = 0.03), no relationship with treatment factors was
      detected. In multivariate regression analysis, abdominal adiposity (P = 0.001),
      but not overweight/obesity by BMI status nor HI/aGT, was associated with
      significantly lower 25OHD concentrations. CONCLUSIONS: Adult survivors are at
      increased risk of abnormalities in vitamin D compared to the background
      population, probably reflecting longer time since diagnosis. Like others, we have
      not identified any contributory treatment-related factors. Vitamin D deficiency
      does not appear to be associated with the development of abnormal glucose
      tolerance in this population.

PMID- 25598520
TI  - [A history of antipsychotic long-acting injections in the treatment of
      schizophrenia].
AB  - From a historical perspective, this article describes the use of antipsychotic
      long-acting injections (LAI) in the treatment of schizophrenia, a disorder that
      was defined in the final years of the 19th century. An efficient treatment for
      schizophrenia was discovered only in 1952 with the introduction of
      chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became
      available as LAI. The first compounds were fluphenazine enanthate (1966) and
      decanoate (1968) whose development is attributed to G.R. Daniel, a medical
      director at Squibb & Sons. Other first-generation antipsychotics long-acting
      injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and
      1970s. FGA-LAIs made a key contribution to the development of community
      psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to
      ensure that patients could be taken care of in outpatient facilities. FGA-LAIs
      prevented covert non-compliance. Compliance was further reinforced by the social
      and psychological support of patients. The introduction of second-generation
      antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by
      a drop in the number of papers published on this topic. The interest in LAI was
      revived with the introduction of the first SGA-LAI in 2003. Four different
      preparations have been approved in the decade between 2003 and 2013. SGA-LAIs
      differ from FGA-LAIs in the technology that is used to produce the depot effect,
      and also in the treatment objectives. The rationale for using SGA-LAIs is not
      only to prevent relapses due to treatment interruption, but also to achieve more
      constant plasma levels in order to reduce side effects due to excessive plasma
      levels and loss of efficacy due to insufficient plasma levels. Also, treatment
      objectives are no longer limited to controlling acute symptoms. Treatment
      objectives now include the alleviation of negative symptoms and cognitive
      deficits that are key prognostic factors.

PMID- 25598521
TI  - Preclinical evaluations on the efficacy of a topical Chinese herbal formula for
      swelling control and pain relief.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Patients suffering from musculoskeletal pain and
      swellings occupy many hospital beds and demand many rehabilitation facilities.
      Chinese Medicine is offering many alternatives to ameliorate pain and swelling.
      However, evidence-based scientific publications supporting their efficacy on pain
      relief are inadequate. The in vitro and in vivo efficacy of a topical use Chinese
      herbal bath formula (HB) on anti-inflammation and swelling control was studied.
      MATERIALS AND METHODS: The therapeutic mechanisms of HB were studied in vitro via
      anti-inflammatory and pro-angiogenic assays on RAW264.7 and HUVEC cells,
      respectively. Fibroblast proliferation was also studied with Hs27 cells. The in
      vivo angiogenic effect of HB was also studied using zebrafish model, while its
      efficacy of in vivo anti-Inflammation and swelling control were investigated
      using rat paw edema model. The affected paw was treated by immersing it in the HB
      or distilled water as control. The sensation of pain, change in paw thickness and
      inflammation marker in serum were analyzed. RESULTS: In the anti-inflammation
      assay, HB significantly inhibited nitrite release from RAW264.7 by 47.6% at 800
      MUg/ml. In the pro-angiogenic assays, it reduced wound area in HUVEC by 8.2% and
      increased tube formation of HUVEC by 11.5% at 300 MUg/ml. HB also stimulated Hs27
      proliferation up to 23.5% at 1200 MUg/ml. It showed in vivo pro-angiogenic effect
      by increasing the mean sprout number in the embryos of zebrafish by 2.4 folds.
      The in vivo therapeutic effects of HB on edema was illustrated by the significant
      longer thermal withdrawal latency and thinner paw thickness compared with
      control. After 14 days of treatment, HB also reduced the IL-6 concentration in
      the serum of rat by 20.9% significantly. CONCLUSIONS: This study showed that HB
      is effective for swelling control and pain relief from edema due to its anti
      inflammatory and pro-angiogenic properties.

PMID- 25598522
TI  - Genetic contribution of catechol-O-methyltransferase in hippocampal structural
      and functional changes of female migraine sufferers.
AB  - Physiological and emotional stressors are associated with or provoke each
      migraine attack and cause structural and functional changes in the central
      nervous system. The hippocampus, a limbic structure important in anxiety-related
      behavior, is vulnerable to long-term stress. Given that catechol-O
      methyltransferase (COMT) is widely distributed in the hippocampus and its genetic
      variation is thought to contribute to the interindividual variability in pain
      perception and anxiety regulation, whether or not migraine and COMT val(158) met
      genotype have an interactive effect in the key brain area related to maladaptive
      stress, the hippocampus, is still poorly understood. Using T1-weighted and
      resting functional MRI, we evaluated the effect of COMT genetic variations on
      migraine and possible interactions between COMT and the disease in brain
      structure and function in 135 females with migraine without aura (MWoA) and 111
      matched health controls (HC). Optimized voxel-based morphometry (VBM) and
      functional connectivity (FC) analyses were applied. From the whole brain VBM
      analysis, we found a significant disease * genotype interaction in the
      hippocampus, which overlapped with disease-related increase of gray matter (GM)
      in val homozygote migraineurs. In our results, increased GM in the hippocampus
      was only found in val homozygote MWoA compared to val homozygote HC. Moreover, FC
      between the hippocampus and the medial prefrontal cortex was significantly
      decreased in val homozygotes, and it was negatively correlated with self-rating
      anxiety scale values.Our results indicated that brain structure and function of
      the hippocampus are differentially affected by migraine in val homozygotes
      compared with met carriers.

PMID- 25598523
TI  - Dominance relationships among siamang males living in multimale groups.
AB  - Intense intolerance among males is considered to be an important mechanism
      maintaining the uni-male organization traditionally attributed to socially
      monogamous gibbons. Long-term field work, however, has revealed the existence of
      stable, socially polyandrous groups in at least two populations, raising
      questions about the mechanism that allows two adult males to co-reside in the
      same group. I collected 21 months of behavioral data on 7 two-male groups of wild
      siamangs (Symphalangus syndactylus) in southern Sumatra (Indonesia) to test the
      hypothesis that dominance relationships regulate the interactions of adult male
      siamangs and ultimately facilitate multi-male social groups. A dominant male
      could clearly be identified in each dyad, based on a consistent direction of
      agonistic interactions, displacements and the maintenance of an advantageous
      position in the canopy. Males identified as dominant enjoyed greater social
      access to the resident female and monopolized copulations. These results suggest
      that gibbons possess the psycho-social flexibility to regulate intra-sexual
      aggression and live in multi-male social units under certain social conditions. I
      discuss the effects that relatedness between males and female choice have in
      determining this grouping pattern, and the role of male intolerance in the
      maintenance of primate mating systems.

PMID- 25598524
TI  - Pentimento: Neural Crest and the origin of mesectoderm.
AB  - The Neural Crest, a transient epithelium in vertebrate embryos, is the source of
      putative stem cells known to give rise to neuronal, glial and endocrine
      components of the peripheral (sensory, autonomic and enteric) nervous system
      (PNS) and pigment cells in the skin. The Neural Crest is also widely believed to
      be the source of mesectodermal derivatives (skeletogenic, odontogenic, connective
      tissue and smooth muscle mesenchyme) in the vertebrate head [see (Bronner and
      LeDouarin, 2012; Le Douarin, 2012; Le Douarin and Kalcheim, 1999); see also
      (Horstadius, 1950; Weston, 1970)]. This conventional understanding of the broad
      developmental potential of the Neural Crest has been challenged over the past few
      years (Breau et al., 2008; Lee et al., 2013a, 2013b; Weston et al., 2004), based
      on recognition that the definition of the embryonic epithelia that comprise the
      Neural Crest may be imprecise. Indeed, the definition of the embryonic tissues
      understood to constitute the Neural Crest has changed considerably since it was
      first described by Wilhelm His 150 years ago (His, 1868). Today, the operational
      definition of the Neural Crest is inconsistent and functionally ambiguous. We
      believe that more precise definitions of the embryonic tissues involved in Neural
      Crest development would be useful to understand (1) the range of cellular
      phenotypes that actually segregate from it, (2) when this lineage diversification
      occurs, and (3) how diversification is regulated. In this idiosyncratic review,
      we aim to explain our concerns with the current definitions in this field, and in
      the chiastic words of Samuel Johnson (1781), "... make new things familiar and
      familiar things new".(1) Then, we will try to distinguish the developmental
      events crucial to the regulation of Neural Crest development at both cranial and
      trunk axial levels of vertebrate embryos, and address some of the implicit
      assumptions that underlie the conventional interpretation of experimental results
      on the origin and fates of Neural Crest-derived cells. We hope our discussion
      will resolve some ambiguities regarding both the range of derivatives in the
      Neural Crest lineage and the conventional understanding that cranial
      mesectodermal derivatives share a common Neural Crest-derived lineage precursor
      with components of the PNS. 

PMID- 25598525
TI  - Delayed gratification is better than no gratification.

PMID- 25598526
TI  - A self-adaptive triple-branched stent graft for arch repair during open type A
      dissection surgery.
AB  - OBJECTIVE: To make the open placement of the triple-branched stent graft
      technique suitable for most patients with acute type A aortic dissection to
      achieve effective individual total arch repair, we developed a self-adaptive
      triple-branched stent graft and arch open technique. In this study, we report the
      clinical experience and outcomes of total arch repair using implantation of this
      self-adaptive triple-branched stent graft with the aid of the arch open
      technique. METHODS: Between December 2012 and July 2014, 105 consecutive patients
      with acute type A aortic dissection with indications of total arch repair
      underwent total arch repair using implantation of a self-adaptive triple-branched
      stent graft with the aid of the arch open technique under hypothermic
      cardiopulmonary bypass and selective cerebral perfusion. Survivors were followed
      up prospectively by means of computed tomography angiography. RESULTS: The
      cardiopulmonary bypass time was 169.37 +/- 27.17 minutes, aortic crossclamp time
      was 60.48 +/- 16.72 minutes, and selective cerebral perfusion and lower body
      arrest time was 28.95 +/- 7.23 minutes. The in-hospital mortality was 4.76%. One
      patient was lost to follow-up. One sudden death of unknown cause occurred 10
      months after surgery. On the 3-month postoperative scans, the false lumen closed
      with complete thrombus formation around the self-adaptive triple-branched stent
      graft was found in all survivors and at the diaphragmatic level in 71.72% of
      patients. CONCLUSIONS: The simple implantation of a self-adaptive triple-branched
      stent graft with the aid of the arch open technique can be used safely in most
      patients with acute type A aortic dissection for effective individual total arch
      repair.

PMID- 25598527
TI  - "How am I doing? Just ask me!" The usefulness of patient self-reported quality of
      life in thoracic surgery.

PMID- 25598528
TI  - Improved detection of stage I non-small cell lung cancer with a serum-based
      assay.

PMID- 25598529
TI  - Robust manipulation of superconducting qubits in the presence of fluctuations.
AB  - Superconducting quantum systems are promising candidates for quantum information
      processing due to their scalability and design flexibility. However, the
      existence of defects, fluctuations, and inaccuracies is unavoidable for practical
      superconducting quantum circuits. In this paper, a sampling-based learning
      control (SLC) method is used to guide the design of control fields for
      manipulating superconducting quantum systems. Numerical results for one-qubit
      systems and coupled two-qubit systems show that the "smart" fields learned using
      the SLC method can achieve robust manipulation of superconducting qubits, even in
      the presence of large fluctuations and inaccuracies. 

PMID- 25598531
TI  - Antiviral immunity. Dual attack by RIG-I.
AB  - RIG-I induces a type III interferon response during hepatitis B virus infection
      and also directly interferes with viral replication.

PMID- 25598530
TI  - Brain metastases in gestational trophoblast neoplasia: an update on incidence,
      management and outcome.
AB  - OBJECTIVE: To update the demographic data, treatment details and outcomes for GTN
      patients with brain metastases managed with the modern treatment protocols at the
      UK centre for gestational trophoblast neoplasia at Charing Cross Hospital in
      London. METHODS: The hospital database and pharmacy records were reviewed to
      identify GTN patients treated with brain metastases. Data was assembled on the
      specific GTN diagnosis, staging, prognostic scores, chemotherapy regimens,
      additional interventions and outcomes. RESULTS: During the 22 year study period,
      27 GTN patients with brain metastases were treated. One case clearly resulted
      from a prior molar pregnancy, 3 were of uncertain aetiology and 23 cases had no
      prior molar pregnancy. The standard chemotherapy regimens were EMA-CO or EMA-EP
      given with an enhanced CNS methotrexate dose combined with intrathecal
      methotrexate. Five patients required emergency neurosurgery and routine
      radiotherapy was not employed. Twenty three (85%) patients are long term
      survivors and four patients died. Of the patients who died, all four had
      chemotherapy refractive disease and two had extended intervals of 18 and 30 years
      from their antecedent pregnancy. CONCLUSION: The incidence of brain metastases in
      postmolar pregnancy GTN is extremely low. Patients with non-molar choriocarcinoma
      have an approximate 20% risk of CNS disease and should have routine CNS imaging.
      Treatment with CNS doses of EMA-CO or EMA-EP appears curative for most patients.

PMID- 25598532
TI  - Cell death. Silencing the immune response of apoptotic cells.
AB  - Mitochondrial DNA released during apoptosis triggers a type I interferon response
      that is held in check by the apoptotic caspases.

PMID- 25598533
TI  - Regulatory T cells. The PTEN stabilizer.
AB  - PTEN maintains regulatory T cell lineage stability and immune homeostasis.

PMID- 25598535
TI  - The thermodynamic driving force for kinetics in general and enzyme kinetics in
      particular.
AB  - The thermodynamic driving force of a reaction is usually taken as the chemical
      potential difference between products and reactants. The forward and backward
      reaction rates are then related to this force. This procedure is of very limited
      validity, as the resulting expression contains no kinetic factor and gives little
      information on reaction kinetics. The transformation of the reaction rate as a
      function of concentration (and temperature) into a function of chemical potential
      should be more properly performed, as illustrated by a simple example of an
      enzymatic reaction. The proper thermodynamic driving force is the difference
      between the exponentials of the totaled chemical potentials of reactants and
      products. 

PMID- 25598534
TI  - Survival after squamous cell and basal cell carcinoma of the skin: A
      retrospective cohort analysis.
AB  - A retrospective cohort analysis of survival after keratinocyte cancer (KC) was
      conducted using data from a large, population-based case-control study of KC in
      New Hampshire. The original study collected detailed information during personal
      interviews between 1993 and 2002 from individuals with squamous (SCC) and basal
      (BCC) cell carcinoma, and controls identified through the Department of
      Transportation, frequency-matched on age and sex. Participants without a history
      of non-skin cancer at enrolment were followed as a retrospective cohort to assess
      survival after either SCC or BCC, or a reference date for controls. Through 2009,
      cancers were identified from the New Hampshire State Cancer Registry and self
      report; death information was obtained from state death certificate files and the
      National Death Index. There were significant differences in survival between
      those with SCC, BCC and controls (p = 0.040), with significantly greater risk of
      mortality after SCC compared to controls (adjusted hazard ratio [HR] 1.25; 95%
      confidence interval 1.01-1.54). Mortality after BCC was not significantly altered
      (HR 0.96; 95% CI 0.77-1.19). The excess mortality after SCC persisted after
      adjustment for numerous personal risk factors including time-varying non-skin
      cancer occurrence, age, sex and smoking. Survival from the date of the
      intervening cancer, however, did not vary (HR for SCC 0.98; 95% CI 0.70-1.38).
      Mortality also remained elevated when individuals with subsequent melanoma were
      excluded (HR for SCC 1.30; 95% CI 1.05-1.61). Increased mortality after SCC
      cannot be explained by the occurrence of intervening cancers, but may reflect a
      more general predisposition to life threatening illness that merits further
      investigation.

PMID- 25598537
TI  - Recent developments in enzyme promiscuity for carbon-carbon bond-forming
      reactions.
AB  - Numerous enzymes have been found to catalyze additional and completely different
      types of reactions relative to the natural activity they evolved for. This
      phenomenon, called catalytic promiscuity, has proven to be a fruitful guide for
      the development of novel biocatalysts for organic synthesis purposes. As such,
      enzymes have been identified with promiscuous catalytic activity for, one or
      more, eminent types of carbon-carbon bond-forming reactions like aldol couplings,
      Michael(-type) additions, Mannich reactions, Henry reactions, and Knoevenagel
      condensations. This review focuses on enzymes that promiscuously catalyze these
      reaction types and exhibit high enantioselectivities (in case chiral products are
      obtained). 

PMID- 25598536
TI  - Climbing fiber receptive fields-organizational and functional aspects and
      relationship to limb coordination.
AB  - Climbing fiber receptive fields are a physiological marker that have proven
      useful to delineate the details of the olivocerebellar circuitry. They have also
      proven useful as a point of reference to delineate the organization of other
      parts of the cerebellar circuitry. But what does the location of the climbing
      fiber receptive field imply and what is its relation to the presumed role of the
      cerebellum in coordination? Can we expect that all climbing fibers have a
      peripheral receptive field on the skin? In this short review, we aim to cover
      these issues. 

PMID- 25598539
TI  - Ultrasound-mediated method for rapid delivery of nano-particles into cells for
      intracellular surface-enhanced Raman spectroscopy and cancer cell screening.
AB  - Surface-enhanced Raman spectroscopy (SERS) is a powerful technology for providing
      finger-printing information of cells. A big challenge has been the long time
      duration and inefficient uptake of metal nano-particles into living cells as
      substrate for SERS analysis. Herein, a simple method (based on ultrasound) for
      the rapid transfer of silver nanoparticles (NPs) into living cells for
      intracellular SERS spectroscopy was presented. In this study, the ultrasound
      mediated method for NP delivery overcame the shortcoming of 'passive uptake', and
      achieved quick acquisition of reproducible SERS spectra from living human
      nasopharyngeal carcinoma cell lines (C666 and CNE1) and normal nasopharyngeal
      cell line (NP69). Tentative assignment of the Raman bands in the measured SERS
      spectra showed cancer cell specific biomolecular differences, including
      significantly lower DNA concentrations and higher protein concentrations in
      cancerous nasopharyngeal cells as compared to those of normal cells. Combined
      with PCA-LDA multivariate analysis, ultrasound-mediated cell SERS spectroscopy
      differentiated the cancerous cells from the normal nasopharyngeal cells with high
      diagnostic accuracy (98.7%), demonstrating great potential for high-throughput
      cancer cell screening applications. 

PMID- 25598541
TI  - ON CLASSES OF EQUIVALENCE AND IDENTIFIABILITY OF AGE-DEPENDENT BRANCHING
      PROCESSES.
AB  - Age-dependent branching processes are increasingly used in analyses of biological
      data. Despite being central to most statistical procedures, the identifiability
      of these models has not been studied. In this paper, we partition a family of age
      dependent branching processes into equivalence classes over which the
      distribution of the population size remains identical. This result is applicable
      to study identifiability of the offspring and lifespan distributions for
      parametric families of branching processes. For example, we identify classes of
      Markov processes that are not identifiable. We show that age-dependent processes
      with (non-exponential) gamma distributed lifespan are identifiable and that Smith
      Martin processes are not always identifiable.

PMID- 25598538
TI  - Modulation of the intestinal microbiota is associated with lower plasma
      cholesterol and weight gain in hamsters fed chardonnay grape seed flour.
AB  - The relationship between the intestinal microbiota and the hypocholesterolemic
      and antiobesity effects of whole grape seed flour from white and red winemaking
      was evaluated. Male Golden Syrian hamsters were fed a high-fat (HF) control diet
      or a HF diet supplemented with 10% partially defatted grape seed flours from
      either Chardonnay (ChrSd) or Cabernet Sauvignon (CabSd) grapes for 3 weeks. The
      numbers of total bacteria and relative abundances of Bifidobacterium spp.,
      Lactobacillus spp., and Firmicutes in feces were significantly lower, while the
      relative abundance of Bacteroides fragilis was greater than the control from
      feeding the ChrSd diet. The ratio of Firmicutes/Bacteroidetes (F/B) was lower in
      the ChrSd diet. There were significantly positive correlations between
      Lactobacillus spp., ratio of F/B, and plasma total- and LDL-cholesterol and liver
      weight. The reduction of Lactobacillus spp. by the ChrSd diet was accompanied by
      inhibition of Farnesoid X receptor (FXR) signaling in the intestine as expression
      of intestinal fibrablast growth factor (FGF)15, positively regulated by FXR, was
      decreased. Expression of CYP7A1, negatively regulated by FGF15, was up-regulated
      in the liver, which indicates that alteration of the intestinal microbiota may
      regulate bile acid and lipid metabolism. These findings suggest that beneficial
      health effects of Chardonnay grape seed flour on HF-induced metabolic disease
      relate in part to modulation of intestinal microbiota and their metabolic
      processes.

PMID- 25598542
TI  - With whom to dine? Ravens' responses to food-associated calls depend on
      individual characteristics of the caller.
AB  - Upon discovering food, common ravens, Corvus corax, produce far-reaching 'haa'
      calls or yells, which are individually distinct and signal food availability to
      conspecifics. Here, we investigated whether ravens respond differently to 'haa'
      calls of known and unknown individuals. In a paired playback design, we tested
      responses to 'haa' call sequences in a group containing individually marked free
      ranging ravens. We simultaneously played call sequences of a male and a female
      raven in two different locations and varied familiarity (known or unknown to the
      local group). Ravens responded strongest to dyads containing familiar females,
      performing more scan flights above and by perching in trees near the respective
      speaker. Acoustic analysis of the calls used as stimuli showed no sex-, age- or
      familiarity-specific acoustic cues, but highly significant classification results
      at the individual level. Taken together, our findings indicate that ravens
      respond to individual characteristics in 'haa' calls, and choose whom to approach
      for feeding, i.e. join social allies and avoid dominant conspecifics. This is the
      first study to investigate responses to 'haa' calls under natural conditions in a
      wild population containing individually marked ravens.

PMID- 25598543
TI  - The role of social attraction and its link with boldness in the collective
      movements of three-spined sticklebacks.
AB  - Social animals must time and coordinate their behaviour to ensure the benefits of
      grouping, resulting in collective movements and the potential emergence of
      leaders and followers. However, individuals often differ consistently from one
      another in how they cope with their environment, a phenomenon known as animal
      personality, which may affect how individuals use coordination rules and
      requiring them to compromise. Here we tracked the movements of pairs of three
      spined sticklebacks, Gasterosteus aculeatus, separated by a transparent partition
      that allowed them to observe and interact with one another in a context
      containing cover. Individuals differed consistently in their tendency to approach
      their partner's compartment during collective movements. The strength of this
      social attraction was positively correlated with the behavioural coordination
      between members of a pair but was negatively correlated with an individual's
      tendency to lead. Social attraction may form part of a broader behavioural
      syndrome as it was predicted by the boldness of an individual, measured in
      isolation prior to the observation of pairs, and by the boldness of the partner.
      We found that bolder fish, and those paired with bolder partners, tended to
      approach their partner's compartment less closely. These findings provide
      important insights into the mechanisms that govern the dynamics and functioning
      of social groups and the emergence and maintenance of consistent behavioural
      differences.

PMID- 25598544
TI  - EXPLAINING THE ASSOCIATION BETWEEN INCARCERATION AND DIVORCE.
AB  - Recent studies have suggested that incarceration dramatically increases the odds
      of divorce, but we know little about the mechanisms that explain the association.
      This study uses prospective longitudinal data from a subset of married young
      adults in the National Longitudinal Study of Adolescent Health (N = 1,919) to
      examine whether incarceration is associated with divorce indirectly via low
      marital love, economic strain, relationship violence, and extramarital sex. The
      findings confirmed that incarcerations occurring during, but not before, a
      marriage were associated with an increased hazard of divorce. Incarcerations
      occurring during marriage also were associated with less marital love, more
      relationship violence, more economic strain, and greater odds of extramarital
      sex. Above-average levels of economic strain were visible among respondents
      observed preincarceration, but only respondents observed postincarceration showed
      less marital love, more relationship violence, and higher odds of extramarital
      sex than did respondents who were not incarcerated during marriage. These
      relationship problems explained approximately 40 percent of the association
      between incarceration and marital dissolution. These findings are consistent with
      theoretical predictions that a spouse's incarceration alters the rewards and
      costs of the marriage and the relative attractiveness of alternative partners.

PMID- 25598545
TI  - 'A WONDERFULL MONSTER BORNE IN GERMANY': HAIRY GIRLS IN MEDIEVAL AND EARLY MODERN
      GERMAN BOOK, COURT AND PERFORMANCE CULTURE.
AB  - Human hirsuteness, or pathological hair growth, can be symptomatic of various
      conditions, including genetic mutation or inheritance, and some cancers and
      hormonal disturbances. Modern investigations into hirsuteness were initiated by
      nineteenth-century German physicians. Most early modern European cases of
      hypertrichosis (genetically determined all-over body and facial hair) involve
      German-speaking parentage or patronage, and are documented in German print
      culture. Through the Wild Man tradition, modern historians routinely link early
      modern reception of historical hypertrichosis cases to issues of ethnicity
      without, however, recognising early modern awareness of links between temporary
      hirsuteness and the pathological nexus of starvation and anorexia. Here, four
      cases of hirsute females are reconsidered with reference to this medical
      perspective, and to texts and images uncovered by my current research at the
      Herzog August Library and German archives. One concerns an Italian girl taken to
      Prague in 1355 by the Holy Roman Empress, Anna von Schweidnitz. Another focuses
      on Madeleine and Antonietta Gonzalez, daughters of the 'Wild Man' of Tenerife,
      documented at German courts in the 1580s. The third and fourth cases consider the
      medieval bearded Sankt Kummernis (also known as St Wilgefortis or St Uncumber),
      and the seventeenth-century Bavarian fairground performer Barbara Urslerin.
      Krankhafter menschlicher Hirsutismus kann aufgrund unterschiedlicher Ursachen
      auftreten, zu denen u.a. genetische Velanderungen und Vererbung, verschiedene
      Krebserkrankungen und hormonelle Storungen gehoren. Die moderne Hirsutismus
      Forschung ist im 19. Jh. von deutschen Forschern initiiert worden. Die meisten
      europaischen fruhneuzeitlichen Erscheinungen von Hypertrichose (dem genetisch
      bedingten Haarwuchs am gesamten Korper und im Gesicht) gehen auf deutschsprachige
      Eltern oder Forderer zuruck und sind in Deutschland in den Druck gelangt. Bei
      Untersuchungen des Motivs des Wilden Mannes zieht die aktuelle
      geschichtswissenschaftliche Forschung in der Regel Verbindungslinien zwischen der
      fruhneuzeitlichen Wahrnehmung von Hypertrichose-Fallen und Fragen der Ethnizitat,
      ohne jedoch zu beachten, dass in der Fruhen Neuzeit die Verbindung zwischen
      temporarem Hirsutismus und der krankhaften Verknupfung von Unterernahrung und
      Anorexie bekannt war. Im vorliegenden Beitragwerden vier Falle von an Hirsutismus
      erkrankten Frauen neu analysiert, unter Einbezug dieser medizinischen Perspektive
      und unter Beachtung von Texten und Abbildungen, die meine jungsten Forschungen in
      der Herzog August Bibliothek und an deutschen Archiven ans Licht gefordert haben.
      Die hier betrachteten Falle betreffen ein italienisches Madchen, das 1355 von
      Anna von Schweidnitz, Kaiserin des Hl. Romischen Reichs, nach Prag gebracht
      wurde; Madeleine und Antonietta Gonzalez, die Tochter des 'Wilden Manns' von
      Teneriffa, die in den 1580er Jahren an deutschen Hofen bezeugt sind; die bartige
      Sankt Kummernis (Wilgefortis), und die bayerische Jahrmarktkunstlerin Barbara
      Urslerin.

PMID- 25598546
TI  - The Quiet Migration Redux: International Adoption, Race, and Difference.
AB  - Demographers frame international adoption primarily as an unusual kind of
      migration. This insight offers anthropologists new ways to think about kinship.
      Drawing on demographic scholarship and anthropological kinship and migration
      studies, this article develops a new and hybrid approach to international
      adoption as a complex social process that is both migratory and productive of
      kinship. Viewing international adoption as a form of migration reveals how the
      stated "push factors" and actual "pull factors" of international adoption do not
      align perfectly. Using an anthropological life course perspective, the article
      then explores how the experiences of these "migrants" and those close to them,
      over time, are better understood as racialization than solely the product of
      migration. Looking at adoptees' lives through a migration lens reveals some of
      the persistent discomforts that prevent open conversations about racial
      difference and minority status in an adoptive context, that is, one where
      children have been caused to migrate, recruited into families. This article draws
      on data from ethnographic fieldwork with Spanish parents who have adopted
      Peruvian children to argue that international adoption is a unique form of
      immigration that produces a minority category within a majority population.

PMID- 25598547
TI  - Enslaved ants: not as helpless as they were thought to be.
AB  - Slavery in ants involves robbing of brood of host ant species and rearing
      captured individuals in the enslaver's nest. Whereas slaves of facultative slave
      makers increase the workforce of the colony, in obligate slave-makers presence of
      slaves is vital for colony survival. Until recently, it was generally believed
      that enslaved workers act solely for the benefit of their social parasite and are
      wholly lost for their own colony and population. However, evidence that slaves
      may act also in favour of their own maternal population by engaging in various
      forms of the so-called slave rebellions is already quite extensive and may be
      found in both old and recent myrmecological literature, although, unfortunately,
      these data are often neglected or overlooked. They may be classified into four
      categories: (1) acts of physical aggression directed by slaves to slave-makers,
      (2) attempts of slaves to reproduce within a slave-maker colony, (3) 'sabotage',
      i.e. activities of slaves leading to weakening of the slave-maker colony and
      population, and (4) slave emancipation, i.e. partial or complete self-liberation
      of slaves from slave-maker colonies. In this review, we present and discuss all
      these diverse (often interrelated) expressions of slave opposition to their
      enslavers, focussing our discussion on both proximate and evolutionary causation
      of the discussed phenomena. We also indicate some open questions which remain to
      be answered by future research.

PMID- 25598548
TI  - The cavity-nest ant Temnothorax crassispinus prefers larger nests.
AB  - Colonies of the ant Temnothorax crassispinus inhabit mostly cavities in wood and
      hollow acorns. Typically in the field, nest sites that can be used by the ant are
      a limited resource. In a field experiment, it was investigated whether the ants
      prefer a specific size of nest, when different ones are available. In July 2011,
      a total of 160 artificial nests were placed in a beech-pine forest. Four
      artificial nests (pieces of wood with volume cavities, ca 415, 605, 730, and 980
      mm3, respectively) were located on each square meter of the experimental plot.
      One year later, shortly before the emergence of new sexuals, the nests were
      collected. In July 2012, colonies inhabited more frequently bigger nests. Among
      queenright colonies, the ones which inhabited bigger nests had more workers.
      However, there was no relationship between volume of nest and number of workers
      for queenless colonies. Queenright colonies from bigger nests produced more
      sexual individuals, but there was no correlation between number of workers and
      sex allocation ratio, or between volume of nest and sex allocation ratio. In a
      laboratory experiment where ant colonies were kept in 470 and 860 mm3 nests,
      larger colonies allocated more energy to produce sexual individuals. The results
      of this study show the selectivity of T. crassispinus ants regarding the size of
      nest cavity, and that the nest volume has an impact on life history parameters.

PMID- 25598549
TI  - BEEHAVE: a systems model of honeybee colony dynamics and foraging to explore
      multifactorial causes of colony failure.
AB  - A notable increase in failure of managed European honeybee Apis mellifera L.
      colonies has been reported in various regions in recent years. Although the
      underlying causes remain unclear, it is likely that a combination of stressors
      act together, particularly varroa mites and other pathogens, forage availability
      and potentially pesticides. It is experimentally challenging to address causality
      at the colony scale when multiple factors interact. In silico experiments offer a
      fast and cost-effective way to begin to address these challenges and inform
      experiments. However, none of the published bee models combine colony dynamics
      with foraging patterns and varroa dynamics.We have developed a honeybee model,
      BEEHAVE, which integrates colony dynamics, population dynamics of the varroa
      mite, epidemiology of varroa-transmitted viruses and allows foragers in an agent
      based foraging model to collect food from a representation of a spatially
      explicit landscape.We describe the model, which is freely available online
      (www.beehave-model.net). Extensive sensitivity analyses and tests illustrate the
      model's robustness and realism. Simulation experiments with various combinations
      of stressors demonstrate, in simplified landscape settings, the model's
      potential: predicting colony dynamics and potential losses with and without
      varroa mites under different foraging conditions and under pesticide application.
      We also show how mitigation measures can be tested.Synthesis and applications.
      BEEHAVE offers a valuable tool for researchers to design and focus field
      experiments, for regulators to explore the relative importance of stressors to
      devise management and policy advice and for beekeepers to understand and predict
      varroa dynamics and effects of management interventions. We expect that
      scientists and stakeholders will find a variety of applications for BEEHAVE,
      stimulating further model development and the possible inclusion of other
      stressors of potential importance to honeybee colony dynamics.

PMID- 25598550
TI  - Biocrust morphogroups provide an effective and rapid assessment tool for
      drylands.
AB  - Biological soil crusts (biocrusts) occur across most of the world's drylands and
      are sensitive indicators of dryland degradation. Accounting for shifts in
      biocrust composition is important for quantifying integrity of arid and semi-arid
      ecosystems, but the best methods for assessing biocrusts are uncertain. We
      investigate the utility of surveying biocrust morphogroups, a reduced set of
      biotic classes, compared to species data, for detecting shifts in biocrust
      composition and making inference about dryland degradation.We used multivariate
      regression tree (MRT) analyses to model morphogroup abundance, species abundance
      and species occurrence data from two independent studies in semi-arid open
      woodlands of south-eastern Australia. We advanced the MRT method with a 'best
      subsets' model selection procedure, which improved model stability and
      prediction.Biocrust morphogroup composition responded strongly to surrogate
      variables of ecological degradation. Further, MRT models of morphogroup data had
      stronger explanatory power and predictive power than MRT models of species
      abundance or occurrence data. We also identified morphogroup indicators of
      degraded and less degraded sites in our study region.Synthesis and applications.
      Sustainable management of drylands requires methods to assess shifts in
      ecological integrity. We suggest that biocrust morphogroups are highly suitable
      for assessment of dryland integrity because they allow for non-expert, rapid
      survey and are informative about ecological function. Furthermore, morphogroups
      were more robust than biocrust species data, showed a strong response to
      ecological degradation and were less influenced by environmental variation, and
      models of morphogroup abundance were more predictive.

PMID- 25598551
TI  - Differences in Substance Abuse Counselors' Knowledge of Tobacco Cessation
      Medication Effectiveness: 2002-2008.
AB  - Counselors play a supportive role in patients' substance abuse treatment,
      including tobacco cessation. Thus, counselors should be knowledgeable about
      tobacco cessation medications (TCMs). This study examined differences in
      counselors' knowledge of and familiarity with (i.e., diffusion) bupropion and
      nicotine replacement therapy (NRT) between 2002 and 2008 and identified
      predictors of diffusion. Repeated cross-sectional questionnaire data were
      obtained in 2002/04 from 992 counselors and in 2007/08 from 1,226 counselors
      working in private treatment programs. Results indicated that more counselors in
      2007/08 did not know about bupropion to rate its effectiveness than in 2002/04;
      no differences were found for NRT. Among both samples of counselors who were
      familiar with TCMs, effectiveness was rated higher in 2007/08 than in 2002/04.
      Findings suggest that educated and trained counselors are important in diffusing
      TCMs. Knowledgeable counselors may be able to educate patients interested in
      tobacco cessation about available treatments and encourage compliance with TCMs.

PMID- 25598552
TI  - Challenges and Opportunities for Research on Same-Sex Relationships.
AB  - Research on same-sex relationships has informed policy debates and legal
      decisions that greatly affect American families, yet the data and methods
      available to scholars studying same-sex relationships have been limited. In this
      article the authors review current approaches to studying same-sex relationships
      and significant challenges for this research. After exploring how researchers
      have dealt with these challenges in prior studies, the authors discuss promising
      strategies and methods to advance future research on same-sex relationships, with
      particular attention given to gendered contexts and dyadic research designs,
      quasi-experimental designs, and a relationship biography approach. Innovation and
      advances in the study of same-sex relationships will further theoretical and
      empirical knowledge in family studies more broadly and increase understanding of
      different-sex as well as same-sex relationships.

PMID- 25598553
TI  - INTERTEMPORAL DECISION-MAKING FOR A GROUP.
AB  - Temporal discounting assessments measure the reduction in the subjective value of
      a reward as a function of the delay to that reward, and are correlated with
      behavior in social dilemma. Among the solutions proposed for defection in social
      dilemmas is a single individual making the decisions for the group. The present
      study examined the influence of group context on temporal discounting.
      Participants completed temporal discounting procedures when the outcomes affected
      only the individual and when outcomes affected a group of 10, including the
      individual. Though no overall difference was observed between the individual and
      group conditions, sex was found to be a moderating variable: Males discounted
      significantly more when discounting for the individual, but females discounted
      significantly more when discounting for the group. These results indicate that
      sex is an important variable when making intertemporal decisions for a group.

PMID- 25598554
TI  - Adaptation to Externally Driven Change: The Impact of Political Change on Job
      Satisfaction in the Public Sector.
AB  - This article uses a quasi-natural experiment to investigate the adaptation of job
      satisfaction to externally driven political change in the public sector. This is
      important because democratic government bureaucracies often experience changes in
      leadership after elections. The analyses are based on data drawn from a large
      longitudinal data set, the British Household Panel Survey. Findings indicate that
      the impact of political elections is largely weak and temporary and is only
      present for men. For women, the internal processes of the organization tend to be
      more important. These findings suggest that changes in political leadership may
      not be associated with fundamental changes in policy.

PMID- 25598555
TI  - Conformationally Constrained and Nanoparticle Targeted Paclitaxels.
AB  - Paclitaxel (Taxol(r)) is one of the most important anticancer agents developed
      over the last 30 years. Its primary mechanism of action is by interaction with
      the cellular protein tubulin, causing irreversible polymerization to
      microtubules. A detailed knowledge of this crucial interaction is thus of
      paramount importance in the design and development of highly potent analogs and
      also for the potential development of "non-taxane" tubulin polymerization agents.
      This review briefly describes the discovery and development of taxol, and then
      describes our work on delineating the tubulin-binding conformation of paclitaxel
      by a combination of REDOR NMR and molecular modeling. The resulting "T-taxol"
      conformation was validated by the synthesis of conformationally constrained
      paclitaxel analogs, which had bioactivities up to twenty-fold higher than those
      of paclitaxel. The review concludes with recent work on the development of a gold
      nanoparticle derivative of paclitaxel. This delivery method has the potential to
      lower the dosage of paclitaxel needed while maintaining or increasing its
      effectiveness, thus significantly improving the benefits of this important
      chemotherapeutic agent.

PMID- 25598556
TI  - (3+2)-Cycloaddition Reactions of Oxyallyl Cations.
AB  - The (3+2)-cycloaddition reaction involving oxyallyl cations has proven to be a
      versatile and efficient approach for the construction of five-membered carbo- and
      heterocycles, which are prevalent frameworks in natural products and
      pharmaceuticals. The following article will provide a brief summary of recent
      disclosures on this process featuring chemo-, regio- and diastereoselective
      oxyallyl cycloadditions with both electron-rich and electron-deficient 2pi
      partners.

PMID- 25598557
TI  - Drainage-system development in consecutive melt seasons at a polythermal, Arctic
      glacier, evaluated by flow-recession analysis and linear-reservoir simulation.
AB  - [1] The drainage systems of polythermal glaciers play an important role in high
      latitude hydrology, and are determinants of ice flow rate. Flow-recession
      analysis and linear-reservoir simulation of runoff time series are here used to
      evaluate seasonal and inter-annual variability in the drainage system of the
      polythermal Finsterwalderbreen, Svalbard, in 1999 and 2000. Linear-flow
      recessions are pervasive, with mean coefficients of a fast reservoir varying from
      16 (1999) to 41 h (2000), and mean coefficients of an intermittent, slow
      reservoir varying from 54 (1999) to 114 h (2000). Drainage-system efficiency is
      greater overall in the first of the two seasons, the simplest explanation of
      which is more rapid depletion of the snow cover. Reservoir coefficients generally
      decline during each season (at 0.22 h d-1 in 1999 and 0.52 h d-1 in 2000),
      denoting an increase in drainage efficiency. However, coefficients do not exhibit
      a consistent relationship with discharge. Finsterwalderbreen therefore appears to
      behave as an intermediate case between temperate glaciers and other polythermal
      glaciers with smaller proportions of temperate ice. Linear-reservoir runoff
      simulations exhibit limited sensitivity to a relatively wide range of reservoir
      coefficients, although the use of fixed coefficients in a spatially lumped model
      can generate significant subseasonal error. At Finsterwalderbreen, an ice
      marginal channel with the characteristics of a fast reservoir, and a subglacial
      upwelling with the characteristics of a slow reservoir, both route meltwater to
      the terminus. This suggests that drainage-system components of significantly
      contrasting efficiencies can coexist spatially and temporally at polythermal
      glaciers.

PMID- 25598558
TI  - Simulating water markets with transaction costs.
AB  - : This paper presents an optimization model to simulate short-term pair-wise spot
      market trading of surface water abstraction licenses (water rights). The approach
      uses a node-arc multicommodity formulation that tracks individual supplier
      receiver transactions in a water resource network. This enables accounting for
      transaction costs between individual buyer-seller pairs and abstractor-specific
      rules and behaviors using constraints. Trades are driven by economic demand
      curves that represent each abstractor's time-varying water demand. The purpose of
      the proposed model is to assess potential hydrologic and economic outcomes of
      water markets and aid policy makers in designing water market regulations. The
      model is applied to the Great Ouse River basin in Eastern England. The model
      assesses the potential weekly water trades and abstractions that could occur in a
      normal and a dry year. Four sectors (public water supply, energy, agriculture,
      and industrial) are included in the 94 active licensed water diversions. Each
      license's unique environmental restrictions are represented and weekly economic
      water demand curves are estimated. Rules encoded as constraints represent current
      water management realities and plausible stakeholder-informed water market
      behaviors. Results show buyers favor sellers who can supply large volumes to
      minimize transactions. The energy plant cooling and agricultural licenses, often
      restricted from obtaining water at times when it generates benefits, benefit most
      from trades. Assumptions and model limitations are discussed. KEY POINTS:
      Transaction tracking hydro-economic optimization models simulate water
      marketsProposed model formulation incorporates transaction costs and trading
      behaviorWater markets benefit users with the most restricted water access.

PMID- 25598559
TI  - Does substance misuse moderate the relationship between criminal thinking and
      recidivism?
AB  - PURPOSE: Some differential intervention frameworks contend that substance use is
      less robustly related to recidivism outcomes than other criminogenic needs such
      as criminal thinking. The current study tested the hypothesis that substance use
      disorder severity moderates the relationship between criminal thinking and
      recidivism. METHODS: The study utilized two independent criminal justice samples.
      Study 1 included 226 drug-involved probationers. Study 2 included 337 jail
      inmates with varying levels of substance use disorder severity. Logistic
      regression was employed to test the main and interactive effects of criminal
      thinking and substance use on multiple dichotomous indicators of recidivism.
      RESULTS: Bivariate analyses revealed a significant correlation between criminal
      thinking and recidivism in the jail sample (r = .18, p < .05) but no significant
      relationship in the probation sample. Logistic regressions revealed that SUD
      symptoms moderated the relationship between criminal thinking and recidivism in
      the jail-based sample (B = -.58, p < .05). A significant moderation effect was
      not observed in the probation sample. CONCLUSIONS: Study findings indicate that
      substance use disorder symptoms moderate the strength of the association between
      criminal thinking and recidivism. These findings demonstrate the need for further
      research into the interaction between various dynamic risk factors.

PMID- 25598560
TI  - STRONG ORACLE OPTIMALITY OF FOLDED CONCAVE PENALIZED ESTIMATION.
AB  - Folded concave penalization methods have been shown to enjoy the strong oracle
      property for high-dimensional sparse estimation. However, a folded concave
      penalization problem usually has multiple local solutions and the oracle property
      is established only for one of the unknown local solutions. A challenging
      fundamental issue still remains that it is not clear whether the local optimum
      computed by a given optimization algorithm possesses those nice theoretical
      properties. To close this important theoretical gap in over a decade, we provide
      a unified theory to show explicitly how to obtain the oracle solution via the
      local linear approximation algorithm. For a folded concave penalized estimation
      problem, we show that as long as the problem is localizable and the oracle
      estimator is well behaved, we can obtain the oracle estimator by using the one
      step local linear approximation. In addition, once the oracle estimator is
      obtained, the local linear approximation algorithm converges, namely it produces
      the same estimator in the next iteration. The general theory is demonstrated by
      using four classical sparse estimation problems, i.e., sparse linear regression,
      sparse logistic regression, sparse precision matrix estimation and sparse
      quantile regression.

PMID- 25598561
TI  - When need for closure leads to positive attitudes towards a negatively
      stereotyped outgroup.
AB  - The study examined the relationship between epistemic motivation, which is the
      need for closure (NFC), and positive attitudes towards a negatively stereotyped
      outgroup (i.e., Gypsies). Although extensive research has revealed that NFC is
      related to derogatory behavioural tendencies and negative emotions towards
      stereotyped groups, it is proposed that NFC may also be linked to positive
      attitudes towards outgroups. It is predicted, however, that this would be true
      only when NFC is accompanied by a low ability to achieve closure (AAC). It is
      argued that low AAC impairs the construction of schema and their effective
      application. Therefore, NFC in individuals with low AAC may lead them to correct
      their initial tendency to use stereotypes and, as a consequence, to evaluate a
      negatively stereotyped outgroup in a positive way. In this research, low AAC was
      assessed by a scale (Study 1) and experimentally induced (Study 2). In both
      studies, we measured positive attitudes towards Gypsies. The results of the
      studies supported our prediction that NFC is positively related to positive
      attitudes towards Gypsies when AAC is low.

PMID- 25598562
TI  - Male Perpetrators of Intimate Partner Violence and Implicit Attitudes toward
      Violence: Associations with Treatment Outcomes.
AB  - The present study examined the associations among implicit attitudes toward
      factors related to intimate partner violence (IPV) and objective, behavioral
      outcomes of participants legally mandated to attend partner violence
      interventions. Twenty-six male offenders, adjudicated within the past month on
      IPV charges, completed three sets of gender and violence themed implicit
      associations tests (IATs) to evaluate the relationships between implicit
      evaluations of women and violence and three key outcome measures assessed six
      months after enrollment in the study: self-reported prior year IPV perpetration,
      completion of a court-mandated partner abuse program, and criminal reoffending.
      IAT results indicated that more rapid associations between violence-related words
      and positive valences, rather than gender evaluations or associations between
      gender and violence, were associated with greater IPV perpetration during the
      year prior to involvement in the study as well as with poorer outcomes (i.e.,
      greater treatment non-compliance and criminal recidivism) at the 6-month follow
      up. Among explicit measures, only negative partner violence outcome expectancies
      were marginally associated with treatment compliance. None of the explicit
      measures predicted previous violence or recidivism. The findings are discussed in
      the context of reducing violence through promoting implicit cognitive change.

PMID- 25598564
TI  - A Fast EM Algorithm for Fitting Joint Models of a Binary Response and Multiple
      Longitudinal Covariates Subject to Detection Limits.
AB  - Joint modeling techniques have become a popular strategy for studying the
      association between a response and one or more longitudinal covariates. Motivated
      by the GenIMS study, where it is of interest to model the event of survival using
      censored longitudinal biomarkers, a joint model is proposed for describing the
      relationship between a binary outcome and multiple longitudinal covariates
      subject to detection limits. A fast, approximate EM algorithm is developed that
      reduces the dimension of integration in the E-step of the algorithm to one,
      regardless of the number of random effects in the joint model. Numerical studies
      demonstrate that the proposed approximate EM algorithm leads to satisfactory
      parameter and variance estimates in situations with and without censoring on the
      longitudinal covariates. The approximate EM algorithm is applied to analyze the
      GenIMS data set.

PMID- 25598566
TI  - Is the overrepresentation of the poor in child welfare caseloads due to bias or
      need?
AB  - One hanging question in child welfare policy and research is whether there is an
      artificial overrepresentation of the poor in child welfare caseloads or whether
      this reflects the co-occurrence of poverty and need. In order to address this
      question, this study uses data from child welfare (report, assessment, service
      and re-report), income maintenance, special education, hospitals, juvenile court,
      public mental health treatment, and census data. Poor children reported to child
      welfare are compared to non-poor children reported to child welfare and also to
      poor children not reported to child welfare. Poor children reported for
      maltreatment had greater risk factors at the parent and neighborhood levels and
      higher rates of negative outcomes than children in either comparison group. Among
      children reported for maltreatment, poor children have worse outcomes, both
      within child welfare (e.g., recurrence) and outside of child welfare (e.g.
      juvenile court, hospitalization for violence) than non-poor children. These data
      suggest that the overrepresentation of poor children is driven largely by the
      presence of increased risk among the poor children that come to the attention of
      child welfare rather than high levels of systemic class bias.

PMID- 25598563
TI  - Emerging trends in optical sensing of glycemic markers for diabetes monitoring.
AB  - In the past decade, considerable attention has been focused on the measurement of
      glycemic markers, such as glycated hemoglobin and glycated albumin, that provide
      retrospective indices of average glucose levels in the bloodstream. While these
      biomarkers have been regularly used to monitor long-term glucose control in
      established diabetics, they have also gained traction in diabetic screening.
      Detection of such glycemic markers is challenging, especially in a point-of-care
      setting, due to the stringent requirements for sensitivity and robustness. A
      number of non-separation based measurement strategies were recently proposed,
      including photonic tools that are well suited to reagent-free marker
      quantitation. Here, we critically review these methods while focusing on
      vibrational spectroscopic methods, which offer highly specific molecular
      fingerprinting capability. We examine the underlying principles and the utility
      of these approaches as reagentless assays capable of multiplexed detection of
      glycemic markers and also the challenges in their eventual use in the clinic.

PMID- 25598565
TI  - Within-individual correlations reveal link between a behavioral syndrome,
      condition and cortisol in free-ranging Belding's ground squirrels.
AB  - Animals often exhibit consistent individual differences in behavior (i.e. animal
      personality) and correlations between behaviors (i.e. behavioral syndromes), yet
      the causes of those patterns of behavioral variation remain insufficiently
      understood. Many authors hypothesize that state-dependent behavior produces
      animal personality and behavioral syndromes. However, empirical studies assessing
      patterns of covariation among behavioral traits and state variables have produced
      mixed results. New statistical methods that partition correlations into between
      individual and residual within-individual correlations offer an opportunity to
      more sufficiently quantify relationships among behaviors and state variables to
      assess hypotheses of animal personality and behavioral syndromes. In a population
      of wild Belding's ground squirrels (Urocitellus beldingi) we repeatedly measured
      activity, exploration, and response to restraint behaviors alongside
      glucocorticoids and nutritional condition. We used multivariate mixed models to
      determine whether between-individual or within-individual correlations drive
      phenotypic relationships among traits. Squirrels had consistent individual
      differences for all five traits. At the between-individual level, activity and
      exploration were positively correlated whereas both traits negatively correlated
      with response to restraint, demonstrating a behavioral syndrome. At the within
      individual level, condition negatively correlated with cortisol, activity and
      exploration. Importantly, this indicates that although behavior is state
      dependent, which may play a role in animal personality and behavioral syndromes,
      feedback mechanisms between condition and behavior appear not to produce
      consistent individual differences in behavior and correlations between them.

PMID- 25598567
TI  - Prenatal Testosterone and Preschool Disruptive Behavior Disorders.
AB  - Disruptive Behaviors Disorders (DBD), including Oppositional-Defiant Disorder
      (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD), are fairly common and
      highly impairing childhood behavior disorders that can be diagnosed as early as
      preschool. Prenatal exposure to testosterone may be particularly relevant to
      these early-emerging DBDs that exhibit a sex-biased prevalence rate favoring
      males. The current study examined associations between preschool DBD symptom
      domains and prenatal exposure to testosterone measured indirectly via right 2D:4D
      finger-length ratios. The study sample consisted of 109 preschool-age children
      between ages 3 and 6 (64% males;72% with DBD) and their primary caregivers.
      Primary caregivers completed a semi-structured interview (i.e., Kiddie Disruptive
      Behavior Disorder Schedule), as well as symptom questionnaires (i.e., Disruptive
      Behavior Rating Scale, Peer Conflict Scale); teachers and/or daycare providers
      completed symptom questionnaires and children provided measures of prenatal
      testosterone exposure, measured indirectly via finger-length ratios (i.e., right
      2D:4D). Study results indicated a significant association of high prenatal
      testosterone (i.e., smaller right 2D:4D) with high hyperactive-impulsive ADHD
      symptoms in girls but not boys, suggesting that the effect may be driven by, or
      might only exist in, girls. The present study suggests that prenatal exposure to
      testosterone may increase risk for early ADHD, particularly hyperactivity
      impulsivity, in preschool girls.

PMID- 25598568
TI  - Longitudinal Prediction of the One-Year Course of Preschool ADHD Symptoms:
      Implications for Models of Temperament-ADHD Associations.
AB  - Despite the fact that Attention-Deficit/Hyperactivity Disorder (ADHD) is often
      conceptualized as an extreme trait, there remains controversy about the best way
      to understand associations between temperament traits and ADHD. The current study
      examines longitudinal associations between temperament traits and ADHD during
      early childhood in order to critically examine vulnerability and spectrum models
      of trait-ADHD associations. Study participants were 109 children between the ages
      of 3 and 6 and their primary caregivers and teachers/daycare providers, community
      recruited for ADHD-related problems. Primary caregivers completed the Kiddie
      Disruptive Behavior Disorders Schedule semi-structured diagnostic interview at
      the initial appointment and one year later. At the initial appointment, primary
      caregivers completed the Child Behavior Questionnaire as a measure of child
      temperament traits. Results from the initial time point indicated that high
      neuroticism and high surgency were associated with inattentive and hyperactive
      impulsive ADHD symptoms, and low effortful control was associated with
      hyperactive-impulsive ADHD symptoms. However, none of these traits predicted the
      one-year course of ADHD symptoms. Results are more consistent with a spectrum
      (vs. vulnerability) model of trait-psychopathology associations, suggesting that
      traits, but may not influence longitudinal course during early childhood.

PMID- 25598569
TI  - Migration dynamics, entrepreneurship, and African development: Lessons from
      Malawi.
AB  - Using data from Malawi, this study situates the discourse on migration,
      entrepreneurship, and development within the context of Africa's social
      realities. It examines self-employment differences among three groups of migrants
      and corresponding group differences in agricultural and non-agricultural self
      employment. International migrants are found to be more engaged in self
      employment than internal-migrants. However, our results suggest that previous
      findings on the development-related contributions of returning migrants from the
      West need to be appropriately contextualized. When returnees from the West invest
      in self-employment, they typically shy away from Africa's largest economic sector
      - agriculture. In contrast, levels of self-employment, especially in agricultural
      self-employment, are highest among returning migrants and immigrants from other
      African countries, especially from those nearby. We also underscore the gendered
      dimensions of migrants' contribution to African development by demonstrating that
      female migrants are more likely to be self-employed in agriculture than male
      migrants. Furthermore, as human-capital increases, migrants are more likely to
      concentrate their self-employment activities in non-agricultural activities and
      not in the agricultural sector. The study concludes by using these findings to
      discuss key implications for policy and future research.

PMID- 25598570
TI  - A projection-based approach to diffraction tomography on curved boundaries.
AB  - An approach to diffraction tomography is investigated for two-dimensional image
      reconstruction of objects surrounded by an arbitrarily-shaped curve of sources
      and receivers. Based on the integral theorem of Helmholtz and Kirchhoff, the
      approach relies upon a valid choice of the Green's functions for selected
      conditions along the (possibly-irregular) boundary. This allows field projections
      from the receivers to an arbitrary external location. When performed over all
      source locations, it will be shown that the field caused by a hypothetical source
      at this external location is also known along the boundary. This field can then
      be projected to new external points that may serve as a virtual receiver. Under
      such a reformation, data may be put in a form suitable for image construction by
      synthetic aperture methods. Foundations of the approach are shown, followed by a
      mapping technique optimized for the approach. Examples formed from synthetic data
      are provided.

PMID- 25598571
TI  - Novel blends of polylactide with ethylene glycol derivatives of POSS.
AB  - Polylactide (PLA), a main biodegradable and biobased candidate for the
      replacement of petrochemical polymers, is stiff and brittle at room conditions.
      It is therefore of high interest to formulate new PLA-based materials suitable
      for applications demanding flexibility and toughness. In this work, novel blends
      of PLA with polyhedral oligomeric silsesquioxanes (POSS) grafted with longer (P1)
      and shorter (P2) arms of ethylene glycol derivatives were prepared and studied.
      It was hypothesized that, owing to their architecture with the central POSS cage
      grafted with arms, miscibility and stability of the blends could be improved.
      Indeed, PLA/P1 blends were homogeneous despite P1 relatively high Mw of 9,500 g
      mol-1. The blend with 20 wt% of P1, having Tg at 16  degrees C, was transparent
      and flexible, elastomer-like material with excellent drawability. The blend
      remained homogeneous and retained its good drawability as well as flexibility
      during 6 months of aging at room temperature: a 2 % secant modulus of elasticity
      well below 100 MPa, a low yield stress below 2 MPa, and and a large strain at
      break of 8 (800 %). Contary to that, PLA/P2 blends were only partially miscible.
      Nevertheless, owing to the liquid state of the dispersed phase, the blend with 15
      wt% of P2 was transparent and ductile, with Tg at 49  degrees C, a relatively
      high yield strength of 29 MPa, and a large strain at break of 2.3 (230 %). The
      toughening mechanism involved the initiation of crazes and facilitation of their
      propagation by the liquid inclusions via the local plasticization effect.

PMID- 25598572
TI  - Study on the structure of pitch-polymer compositions by fluorescence microscope.
AB  - In this work, the results of studies on the evaluation of colloidal structure of
      coal-tar pitch compositions with selected waste polymers by fluorescence
      microscope. For pitch-polymer compositions containing 10-50 wt% waste polymer,
      softening point, coking value and content of components insoluble in toluene and
      quinoline were carried out. The results indicate that pitch-polymer compositions
      can be treated as microheterogeneous systems, colloidal and biphase, generally
      exhibiting uniform dispersion of particles composed of polymer macromolecules and
      probably of alpha components of coal-tar pitch.

PMID- 25598573
TI  - "When We Learn Better, We Do Better": Describing Changes in Empowerment Through
      Photovoice Among Community Health Advisors in a Breast and Cervical Cancer Health
      Promotion Program in Mississippi and Alabama.

PMID- 25598574
TI  - Personality Traits Elucidate Sex Differences in Attention-Deficit/Hyperactivity
      Disorder Comorbidity During Early Childhood.
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) is highly comorbid with other
      childhood disorders, and there are striking sex differences in this comorbidity,
      particularly during early childhood. For example, boys with ADHD are more likely
      to exhibit comorbid disruptive behavior and neurodevelopmental disorders,
      compared to girls, during early childhood. Yet, explanations for these well
      established sex differences remain in short supply. The current study evaluated
      the novel hypothesis that personality traits may serve as intermediate phenotypes
      that help explain sex differences in common ADHD comorbidity profiles during
      early childhood. Study participants were 109 children between the ages of 3 and 6
      and their primary caregivers and teachers/daycare providers, recruited from the
      community and over-recruited for ADHD-related problems. Primary caregivers
      completed the Child Behavior Checklist, and teachers/daycare providers completed
      the Teacher Report Form as a measure of child behavior problems. Examiners
      completed the California Q-Sort as a measure of child personality traits.
      Moderated mediation analyses suggested that personality traits explain
      associations between ADHD and oppositional-defiance, aggression, and language
      problems in a sex-specific manner. While high neuroticism mediated associations
      between ADHD and oppositional-defiance in girls, disagreeableness mediated
      associations between ADHD and aggression and low conscientiousness mediated
      associations between ADHD and neurodevelopmental language problems in boys. Sex
      differences in trait-psychopathology associations may help explain sex
      differences in comorbidity profiles with possible implications for child
      assessment and personalized early intervention.

PMID- 25598575
TI  - Children's Recall of Generic and Specific Labels Regarding Animals and People.
AB  - Although children tend to categorize objects at the basic level, we hypothesized
      that generic sentences would direct children's attention to different levels of
      categorization. We tested children's and adults' short-term recall (Study 1) and
      longer-term recall (Study 2) for labels presented in generic sentences (e.g.,
      Kids like to play jimjam) versus specific sentences (e.g., This kid likes to play
      jimjam). Label content was either basic level (e.g., cat, boy) or superordinate
      (e.g., animal, kid). As predicted, participants showed better memory for label
      content in generic than specific sentences (short-term recall for children; both
      short and longer-term recall for adults). Errors typically involved recalling
      specific noun phrases as generic, and recalling superordinate labels as basic.
      These results demonstrate that language influences children's representations of
      new factual information, but that cognitive biases also lead to distortions in
      recall.

PMID- 25598576
TI  - Do organizations spend wisely on employees? Effects of training and development
      investments on learning and innovation in organizations.
AB  - The present study examines the effects of training and development on
      organizational innovation. We specifically suggest that the training and
      development investments of an organization affect its innovative performance by
      promoting various learning practices. We empirically tested our hypothesis by
      using time-lagged, multi-source data collected from 260 Korean companies that
      represent diverse industries. Our analysis showed that corporate expenditure for
      internal training predicts interpersonal and organizational learning practices,
      which, in turn, increase innovative performance. The data also revealed that the
      positive relationship between interpersonal and organizational learning practices
      and innovative performance is stronger within organizations that have stronger
      innovative climates. By contrast, investment in employee development through
      financial support for education outside an organization poses a significant
      negative effect on its innovative performance and no significant effect on
      learning practices. The present study provides a plausible explanation for a
      mechanism through which the investment of an organization in employees enhances
      its innovative performance. Copyright (c) 2013 The Authors.

PMID- 25598577
TI  - Letter Knowledge in Parent-Child Conversations.
AB  - Learning about letters is an important component of emergent literacy. We
      explored the possibility that parent speech provides information about letters,
      and also that children's speech reflects their own letter knowledge. By studying
      conversations transcribed in CHILDES (MacWhinney, 2000) between parents and
      children aged one to five, we found that alphabetic order influenced use of
      individual letters and letter sequences. The frequency of letters in children's
      books influenced parent utterances throughout the age range studied, but
      children's utterances only after age two. Conversations emphasized some literacy
      relevant features of letters, such as their shapes and association with words,
      but not letters' sounds. Describing these patterns and how they change over the
      preschool years offers important insight into the home literacy environment.

PMID- 25598578
TI  - Chemical communication and host search in Galerucella leaf beetles.
AB  - Herbivore insects use a variety of search cues during host finding and mate
      recognition, including visual, gustatory, and olfactory stimuli, leaving multiple
      traits for evolution to act upon. However, information about differences or
      similarities in search pattern amongst closely related insect herbivore species
      is still scarce. Here, we study the production of and the response to pheromone
      in Galerucella (Coleoptera: Chrysomelidae) to investigate the beetles' search
      behaviour. Males of G. pusilla and G. calmariensis, two closely related species,
      are known to produce the aggregation pheromone dimethylfuran-lactone when feeding
      on their host plant, whereas no pheromones have been identified in other
      Galerucella species. We show that dimethylfuran-lactone is produced also by males
      of G. tenella, a species phylogenetically close to G. pusilla and G.
      calmariensis, whereas the more distantly related species G. lineola and G.
      sagittariae were not found to produce the same compound. To investigate the
      beetles' behavioural response to dimethylfuran-lactone, the pheromone was
      synthesized using a partly novel method and tested in olfactometers, showing that
      G. pusilla, G. calmariensis, and G. tenella were all attracted to the pheromone,
      whereas G. lineola and G. sagittariae did not respond. This suggests that the
      production of and the response to pheromone could be linked to the phylogenetic
      relatedness between the species.

PMID- 25598579
TI  - Preferences of the peripheral olfactory system of Western Flower Thrips,
      Frankliniella occidentalis towards stereoisomers of common plant volatiles.
AB  - Stereochemistry plays a significant role in structure-activity relationships of
      messenger chemicals. The ability to distinguish between enantiomers and geometric
      isomers, however, may be limited to certain stereoisomeric substances, depending
      on the receiver. In this study, we assessed the preference of the peripheral
      olfactometry system of Western Flower Thrips, F. occidentalis towards
      ubiquitously expressed host compounds, with a goal of establishing whether
      particular stereoisomers enhance host odour recognition. We demonstrate that the
      peripheral olfactory system of a highly polyphagous thysanopteran insect has
      evolved to become highly sensitive to a type of green leaf volatile, which is
      highly ubiquitous in the plant kingdom. We show that there is a significantly
      greater antennal response to the cis isomer, more so than the isomerisation by
      product trans-3-hexen-1-ol. We demonstrate that the antennae of a highly
      polyphagous insect are capable of detecting common plant secondary metabolites in
      both enantiomeric forms.

PMID- 25598580
TI  - Rock Reservoir Properties from the Comprehensive Interpretation of Nuclear
      Magnetic Resonance and Mercury Injection Porosimetry Laboratory Results.
AB  - Combination of laboratory measurements res ults of various properties, i.e.
      porosity, density, permeability and mineral composition, was done to get
      additional factors useful in fluid flow description in the Miocene sandy-shaly
      formation. Special computer processing of nuclear magnetic resonance outcomes and
      mercury injection porosimetry results turned out to be useful in the estimation
      of the relationships facilitating the reservoir characterization and defining new
      helpful factors. Determination of the relationships between groups of quantities
      describing pore space of rock formation was presented as the basis for
      permeability prediction and for relationships extrapolation into interesting
      areas.

PMID- 25598581
TI  - A Probabilistic Approach to Mitigate Composition Attacks on Privacy in Non
      Coordinated Environments.
AB  - Organizations share data about individuals to drive business and comply with law
      and regulation. However, an adversary may expose confidential information by
      tracking an individual across disparate data publications using quasi-identifying
      attributes (e.g., age, geocode and sex) associated with the records. Various
      studies have shown that well-established privacy protection models (e.g., k
      anonymity and its extensions) fail to protect an individual's privacy against
      this "composition attack". This type of attack can be thwarted when organizations
      coordinate prior to data publication, but such a practice is not always feasible.
      In this paper, we introduce a probabilistic model called (d, alpha)-linkable,
      which mitigates composition attack without coordination. The model ensures that d
      confidential values are associated with a quasi-identifying group with a
      likelihood of alpha. We realize this model through an efficient extension to k
      anonymization and use extensive experiments to show our strategy significantly
      reduces the likelihood of a successful composition attack and can preserve more
      utility than alternative privacy models, such as differential privacy.

PMID- 25598582
TI  - In touch - the molecular basis of mechanosensory transduction.
AB  - Nearly all species employ mechanosensitive channels to detect mechanical cues,
      such as touch and sound waves, and convert these mechanical forces into
      electrochemical signals. Genetic, biochemical and electrophysiological studies of
      touch-insensitive mutants in model organisms such as Caenorhabditis elegans and
      Drosophila melanogaster provide insights into the molecular basis of
      mechanosensory transduction.

PMID- 25598583
TI  - Enantiomeric impurities in chiral synthons, catalysts, and auxiliaries. Part 3.
AB  - The enantiomeric excess of chiral reagents used in asymmetric syntheses directly
      affects the reaction selectivity and product purity. In this work, 84 of the more
      recently available chiral compounds were evaluated to determine their actual
      enantiomeric composition. These compounds are widely used in asymmetric syntheses
      as chiral synthons, catalysts, and auxiliaries. These include chiral alcohols,
      amines, amino alcohols, amides, carboxylic acids, epoxides, esters, ketones, and
      oxolanes among other classes of compounds. All enantiomeric test results were
      categorized within five purity levels (i.e. <0.01%, 0.01% to 0.1%, 0.1% to 1%, 1%
      to 10%, and >10%). The majority of the reagents tested were determined to have
      enantiomeric impurities over 0.01%, and two of them were found to contain
      enantiomeric impurities exceeding the 10% level. The most effective
      enantioselective analysis method was a GC approach using a Chiraldex GTA chiral
      stationary phase (CSP). This method worked exceedingly well with chiral amines
      and alcohols.

PMID- 25598584
TI  - Sit-to-stand test: Performance and determinants across the age-span.
AB  - Although the validity of the sit-to-stand (STS) test as a measure of lower limb
      strength has been questioned, it is widely used as such among older adults. The
      purposes of this study were: 1) to describe five-repetition STS test (FRSTST)
      performance (time) by adolescents and adults and 2) to determine the relationship
      of isometric knee extension strength (force and torque), age, gender, weight, and
      stature with that performance. Participants were 111 female and 70 male (14-85
      years) community-dwelling enrollees in the NIH Toolbox Assessment of Neurological
      and Behavioral Function. The FRSTST was conducted using a standard armless chair.
      Knee extension force was measured using a belt-stabilized hand-held dynamometer;
      knee extension torque was measured using a Biodex dynamometer. The mean times for
      the FRSTST ranged from 6.0 sec (20-29 years) to 10.8 sec (80-85 years). For both
      the entire sample and a sub-sample of participants 50-85 years, knee extension
      strength (r = -0.388 to -0.634), age (r = 0.561 and 0.466), and gender (r = 0.182
      and 0.276) were correlated significantly with FRSTST times. In all multiple
      regression models, knee extension strength provided the best explanation of
      FRSTST performance, but age contributed as well. Bodyweight and stature were less
      consistent in explaining FRSTST performance. Gender did not add to the
      explanation of FRSTST performance. Our findings suggest, therefore, that FRSTST
      time reflects lower limb strength, but that performance should be interpreted in
      light of age and other factors.

PMID- 25598585
TI  - Multiple-membership multiple-classification models for social network and group
      dependences.
AB  - The social network literature on network dependences has largely ignored other
      sources of dependence, such as the school that a student attends, or the area in
      which an individual lives. The multilevel modelling literature on school and area
      dependences has, in turn, largely ignored social networks. To bridge this divide,
      a multiple-membership multiple-classification modelling approach for jointly
      investigating social network and group dependences is presented. This allows
      social network and group dependences on individual responses to be investigated
      and compared. The approach is used to analyse a subsample of the Adolescent
      Health Study data set from the USA, where the response variable of interest is
      individual level educational attainment, and the three individual level
      covariates are sex, ethnic group and age. Individual, network, school and area
      dependences are accounted for in the analysis. The network dependences can be
      accounted for by including the network as a classification in the model, using
      various network configurations, such as ego-nets and cliques. The results suggest
      that ignoring the network affects the estimates of variation for the
      classifications that are included in the random part of the model (school, area
      and individual), as well as having some influence on the point estimates and
      standard errors of the estimates of regression coefficients for covariates in the
      fixed part of the model. From a substantive perspective, this approach provides a
      flexible and practical way of investigating variation in an individual level
      response due to social network dependences, and estimating the share of variation
      of an individual response for network, school and area classifications.

PMID- 25598586
TI  - The drivers of month-of-birth differences in children's cognitive and non
      cognitive skills.
AB  - Previous research has found that children who are born later in the academic year
      have lower educational attainment, on average, than children who are born earlier
      in the year, especially at younger ages; much less is known about the mechanisms
      that drive this inequality. The paper uses two complementary identification
      strategies to estimate an upper bound of the effect of age at test by using rich
      data from two UK birth cohorts. We find that differences in the age at which
      cognitive skills are tested accounts for the vast majority of the difference in
      these outcomes between children who are born at different times of the year,
      whereas the combined effect of the other factors (age of starting school, length
      of schooling and relative age) is close to zero. This suggests that applying an
      age adjustment to national achievement test scores may be an appropriate policy
      response to overcome the penalty that is associated with being born later in the
      academic year. Age at test does not, however, explain all of the difference in
      children's view of their own scholastic competence. Age adjusting national
      achievement test scores may help to overcome differences in ability beliefs
      between children who are born at different times of the year, but our results
      suggest that additional policy responses may be required.

PMID- 25598587
TI  - Interviewer effects on non-response propensity in longitudinal surveys: a
      multilevel modelling approach.
AB  - The paper investigates two different multilevel approaches, the multilevel cross
      classified and the multiple-membership models, for the analysis of interviewer
      effects on wave non-response in longitudinal surveys. The models proposed
      incorporate both interviewer and area effects to account for the non-hierarchical
      structure, the influence of potentially more than one interviewer across waves
      and possible confounding of area and interviewer effects arising from the non
      random allocation of interviewers across areas. The methods are compared by using
      a data set: the UK Family and Children Survey.

PMID- 25598588
TI  - Broader health coverage is good for the nation's health: evidence from country
      level panel data.
AB  - Progress towards universal health coverage involves providing people with access
      to needed health services without entailing financial hardship and is often
      advocated on the grounds that it improves population health. The paper offers
      econometric evidence on the effects of health coverage on mortality outcomes at
      the national level. We use a large panel data set of countries, examined by using
      instrumental variable specifications that explicitly allow for potential reverse
      causality and unobserved country-specific characteristics. We employ various
      proxies for the coverage level in a health system. Our results indicate that
      expanded health coverage, particularly through higher levels of publicly funded
      health spending, results in lower child and adult mortality, with the beneficial
      effect on child mortality being larger in poorer countries.

PMID- 25598590
TI  - Is the Indian surgical arena ready for the robotic platform?

PMID- 25598591
TI  - Robotic surgery is ready for prime time in India: For the motion.
AB  - Robotic surgery with its bundled advantages is still in its burgeoning phase, the
      best of which is yet to come. The unrivalled suturing ease and motion scaling
      features, transforming into greater precision, has led to its widespread
      application in different surgical ramifications. These, coupled with the
      aforementioned advantages, has led to an increasing number of procedures being
      performed and that too with improved patient outcomes. It seems that the
      progressing India is readily accepting this robotic surgical innovation, the use
      of which is on a continuous rise, with the number of robotic platforms coming up
      in increasing numbers in many tertiary care Indian centres and a corresponding
      increase in demand of the same by the patients as well; thereby aptly fulfilling
      the economics of 'demand and supply'. 

PMID- 25598592
TI  - Robotic surgery is ready for prime time in India: Against the motion.
AB  - The use of Robotic Surgery as a purported adjunct and aid to Minimal Access
      Surgery (MAS) is growing in several areas. The acknowledged advantages as also
      the obvious and hidden disadvantages of Robotic Surgery are highlighted. Survey
      of literature shows that while Robotic Surgery is "feasible" and the results are
      "comparable" there is no convincing evidence that it is any better than MAS or
      even open surgery in most areas. To move "Robotic Surgery is ready for prime time
      in India" with no less than two dozen robots, many sub-optimally utilized for a
      population of 1.2 billion seems untenable. 

PMID- 25598589
TI  - Associations between prescription opioid injection and Hepatitis C virus among
      young injection drug users.
AB  - OBJECTIVE: Hepatitis C virus (HCV) incidence has been increasing among young
      injection drug users (IDUs). This analysis examined whether the emerging practice
      of prescription opioid (PO) injection is associated with self-reported HCV among
      young IDUs. METHODS: Young IDUs (n = 162) aged 18-25-years-old who indicated
      recent misuse of prescription drugs were sampled in New York and Los Angeles
      during 2009-2011. Participants reported lifetime PO injection history and results
      from their most recent HCV test as well as demographic characteristics and
      lifetime drug use. Bivariate analyses examined relationships between covariates
      and both lifetime PO injection and HCV positivity. Poisson regression examined
      the associations between lifetime PO injection, HCV positivity, and significant
      covariates. RESULTS: A majority reported lifetime PO injection (72.2%) and 30.9%
      self-reported being HCV positive. Lifetime PO injectors were nearly three times
      more likely to report being HCV positive than non-PO injectors (adjusted
      incidence rate ratio (AIRR): 2.69, p<0.05) after controlling for socio
      demographic and other drug use variable. Additionally, substituting POs for
      heroin (AIRR: 2.27, p<0.05), growing up in a lower social class (AIRR: 1.67,
      p<0.05), age (AIRR: 1.12, p<0.05), age of injection initiation (AIRR: 0.87,
      p<0.001), and history of being prescribed stimulants (AIRR: 0.64, p<0.05) were
      independently associated with HCV positivity. CONCLUSIONS: Findings suggest that
      PO injection should be given further consideration as a contributing factor to
      rising HCV infection among young adults in the US.

PMID- 25598593
TI  - Robotic surgical skill acquisition: What one needs to know?
AB  - Robotic surgery has been eagerly adopted by patients and surgeons alike in the
      field of urology, over the last decade. However, there is a lack of
      standardization in training curricula and accreditation guidelines to ensure
      surgeon competence and patient safety. Accordingly, in this review, we aim to
      highlight 'who' needs to learn 'what' and 'how', to become competent in robotic
      surgery. We demonstrate that both novice and experienced open surgeons require
      supervision and mentoring during the initial phases of robotic surgery skill
      acquisition. The experienced open surgeons possess domain knowledge, however,
      need to acquire technical knowledge under supervision (either in simulated or
      clinical environment) to successfully transition to robotic surgery, whereas,
      novice surgeons need to acquire both domain as well as technical knowledge to
      become competent in robotic surgery. With regard to training curricula, a variety
      of training programs such as academic fellowships, mini-fellowships, and mentored
      skill courses exist, and cater to the needs and expectations of postgraduate
      surgeons adequately. Fellowships provide the most comprehensive training,
      however, may not be suitable to all surgeon-learners secondary to the long-term
      time commitment. For these surgeon-learners short-term courses such as the mini
      fellowships or mentored skill courses might be more apt. Lastly, with regards to
      credentialing uniformity in criteria regarding accreditation is lacking but
      earnest efforts are underway. Currently, accreditation for competence in robotic
      surgery is institutional specific. 

PMID- 25598595
TI  - Robotic right colectomy: A worthwhile procedure? Results of a meta-analysis of
      trials comparing robotic versus laparoscopic right colectomy.
AB  - BACKGROUND: Robotic right colectomy (RRC) is a complex procedure, offered to
      selected patients at institutions highly experienced with the procedure. It is
      still not clear if this approach is worthwhile in enhancing patient recovery and
      reducing post-operative complications, compared with laparoscopic right colectomy
      (LRC). Literature is still fragmented and no meta-analyses have been conducted to
      compare the two procedures. This work aims at reducing this gap in literature, in
      order to draw some preliminary conclusions on the differences and similarities
      between RRC and LRC, focusing on short-term outcomes. MATERIALS AND METHODS: A
      systematic literature review was conducted to identify studies comparing RRC and
      LRC, and meta-analysis was performed using a random-effects model. Peri-operative
      outcomes (e.g., morbidity, mortality, anastomotic leakage rates, blood loss,
      operative time) constituted the study end points. RESULTS: Six studies, including
      168 patients undergoing RRC and 348 patients undergoing LRC were considered as
      suitable. The patients in the two groups were similar with respect to sex, body
      mass index, presence of malignant disease, previous abdominal surgery, and
      different with respect to age and American Society of Anesthesiologists score.
      There were no statistically significant differences between RRC and LRC regarding
      estimated blood loss, rate of conversion to open surgery, number of retrieved
      lymph nodes, development of anastomotic leakage and other complications, overall
      morbidity, rates of reoperation, overall mortality, hospital stays. RRC resulted
      in significantly longer operative time. CONCLUSIONS: The RRC procedure is
      feasible, safe, and effective in selected patients. However, operative times are
      longer comparing to LRC and no advantages in peri-operative and post-operative
      outcomes are demonstrated with the use of the robotic surgical system.

PMID- 25598594
TI  - Review of contemporary role of robotics in bariatric surgery.
AB  - With the rise in a number of bariatric procedures, surgeons are facing more
      complex and technically demanding surgical situations. Robotic digital platforms
      potentially provide a solution to better address these challenges. This review
      examines the published literature on the outcomes and complications of bariatric
      surgery using a robotic platform. Use of robotics to perform adjustable gastric
      banding, sleeve gastrectomy, roux-en-y gastric bypass (RYGB), biliopancreatic
      diversion with duodenal switch and revisional bariatric procedures (RBP) is
      assessed. A search on PubMed was performed for the most relevant articles in
      robotic bariatric surgery. A total of 23 articles was selected and reviewed in
      this article. The review showed that the use of robotics led to similar or lower
      complication rate in bariatric surgery when compared with laparoscopy. Two
      studies found a significantly lower leak rate for robotic gastric bypass when
      compared to laparoscopic method. The learning curve for RYGB seems to be shorter
      for robotic technique. Three studies revealed a significantly shorter operative
      time, while four studies found a longer operative time for robotic technique of
      gastric bypass. As for the outcomes of RBP, one study found a lower complication
      rate in robotic arm versus laparoscopic and open arms. Most authors stated that
      the use of robotics provides superior visualisation, more degrees of freedom and
      better ergonomics. The application of robotics in bariatric surgery seems to be a
      safe and feasible option. Use of robotics may provide specific advantages in some
      situations, and overcome limitations of laparoscopic surgery. Large and well
      designed randomised clinical trials with long follow-up are needed to further
      define the role of digital platforms in bariatric surgery. 

PMID- 25598596
TI  - Current status of robotic surgery for rectal cancer: A bird's eye view.
AB  - Minimally invasive surgery for rectal cancer is now widely performed via the
      laparoscopic approach and has been validated in randomized controlled trials to
      be oncologically safe with better perioperative outcomes than open surgery
      including shorter length of stay, earlier return of bowel function, better
      cosmesis, and less analgesic requirement. Laparoscopic surgery, however, has
      inherent limitations due to two-dimensional vision, restricted instrument motion
      and a very long learning curve. Robotic surgery with its superb three-dimensional
      magnified optics, stable retraction platform and 7 degrees of freedom of
      instrument movement offers significant benefits during Total Mesorectal Excision
      (TME) including ease of operation, markedly lower conversion rates and better
      quality of the specimen in addition to shorter (steeper) learning curves. This
      review summarizes the current evidence for the adoption of robotic TME for rectal
      cancer with supporting data from the literature and from the authors' own
      experience. All relevant articles from PubMed using the search terms listed below
      and published between 2000 and 2014 including randomized trials, meta-analyses,
      prospective studies, and retrospective reviews with substantial numbers were
      included. 

PMID- 25598597
TI  - Robotic renal transplantation: Current status.
AB  - INTRODUCTION: Kidney transplantation (KT) has traditionally been performed by
      open renal transplantation, but recently, a few groups including our own have
      described a minimally invasive approach to KT. We aim to discuss the current
      status of robotic kidney transplantation (RKT) and describe our technique of RKT
      with regional hypothermia. MATERIAL AND METHODS: We used the search terms
      "minimally invasive" OR "robotic" OR "robot assisted" AND "kidney
      transplantation." Papers written in English and concerning technical and/or
      clinical outcomes following minimally invasive kidney transplantation were
      selected. Three hundred and eighteen unique articles were retrieved and nine were
      relevant. Comparative outcomes data following RKT with regional hypothermia
      versus open KT (OKT) from our own group were also included. FINDINGS: Nine
      papers, so far, have evaluated the role of robotic approach in KT and have
      conclusively established the feasibility, safety, and reproducibility of RKT,
      although these studies have been performed by experienced robotic surgeons/teams.
      The contemporary published series note that rejection rates were similar in RKT
      and OKT patients. Mean serum creatinine at 6 months in RKT and OKT patients was
      equivalent, across the three series. Most of the studies also note a dramatic
      reduction in the wound-related complication rates. CONCLUSION: RKT appears to be
      a safe surgical alternative to the standard open approach of KT. RKT is
      associated with reduced postoperative pain, analgesic requirement, and better
      cosmesis. RKT, although in its infancy, appears to be associated with lower
      complication rates.

PMID- 25598599
TI  - How small is small enough? Role of robotics in paediatric urology.
AB  - The well-known advantages of robotic surgery include improved dexterity, three
      dimensional operating view and an improved degree of freedom. Robotic surgery is
      performed for a wide range of surgeries in urology, which include radical
      prostatectomy, radical cystectomy, and ureteric reimplantation. Robotic
      paediatric urology is evolving. The major hindrance in the development of
      paediatric robotics is, first, the differences in practice patterns in paediatric
      urology compared with adult urology thereby making development of expertise
      difficult and secondly it is challenging to conduct proper studies in the
      paediatric population because of the paucity of cases. The difficulties in
      conducting these studies include difficulty in designing a proper randomised
      study, difficulties with blinding, and finally, the ethical issues involved,
      finally the instruments although in the phase of evolution require a lot of
      improvement. In this article, we review the relevant articles for paediatric
      robotic surgery. We emphasise on the technical aspects and results in
      contemporary paediatric robotic case series. 

PMID- 25598598
TI  - Robotics in urologic oncology.
AB  - Robotic surgery was initially developed to overcome problems faced during
      conventional laparoscopic surgeries and to perform telesurgery at distant
      locations. It has now established itself as the epitome of minimally invasive
      surgery (MIS). It is one of the most significant advances in MIS in recent years
      and is considered by many as a revolutionary technology, capable of influencing
      the future of surgery. After its introduction to urology, robotic surgery has
      redefined the management of urological malignancies. It promises to make
      difficult urological surgeries easier, safer and more acceptable to both the
      surgeon and the patient. Robotic surgery is slowly, but surely establishing
      itself in India. In this article, we provide an overview of the advantages,
      disadvantages, current status, and future applications of robotic surgery for
      urologic cancers in the context of the Indian scenario. 

PMID- 25598600
TI  - Robotic surgery in gynecology.
AB  - FDA approved Da Vinci Surgical System in 2005 for gynecological surgery. It has
      been rapidly adopted and it has already assumed an important position at various
      centers where this is available. It comprises of three components: A surgeon's
      console, a patient-side cart with four robotic arms and a high-definition three
      dimensional (3D) vision system. In this review we have discussed various robotic
      assisted laparoscopic benign gynecological procedures like myomectomy,
      hysterectomy, endometriosis, tubal anastomosis and sacrocolpopexy. A PubMed
      search was done and relevant published studies were reviewed. Surgeries that can
      have future applications are also mentioned. At present most studies do not give
      significant advantage over conventional laparoscopic surgery in benign
      gynecological disease. However robotics do give an edge in more complex
      surgeries. The conversion rate to open surgery is lesser with robotic assistance
      when compared to laparoscopy. For myomectomy surgery, Endo wrist movement of
      robotic instrument allows better and precise suturing than conventional straight
      stick laparoscopy. The robotic platform is a logical step forward to laparoscopy
      and if cost considerations are addressed may become popular among gynecological
      surgeons world over. 

PMID- 25598601
TI  - Robotic thoracic surgery: The state of the art.
AB  - Minimally invasive thoracic surgery has come a long way. It has rapidly
      progressed to complex procedures such as lobectomy, pneumonectomy, esophagectomy,
      and resection of mediastinal tumors. Video-assisted thoracic surgery (VATS)
      offered perceptible benefits over thoracotomy in terms of less postoperative pain
      and narcotic utilization, shorter ICU and hospital stay, decreased incidence of
      postoperative complications combined with quicker return to work, and better
      cosmesis. However, despite its obvious advantages, the General Thoracic Surgical
      Community has been relatively slow in adapting VATS more widely. The introduction
      of da Vinci surgical system has helped overcome certain inherent limitations of
      VATS such as two-dimensional (2D) vision and counter intuitive movement using
      long rigid instruments allowing thoracic surgeons to perform a plethora of
      minimally invasive thoracic procedures more efficiently. Although the cumulative
      experience worldwide is still limited and evolving, Robotic Thoracic Surgery is
      an evolution over VATS. There is however a lot of concern among established high
      volume VATS centers regarding the superiority of the robotic technique. We have
      over 7 years experience and believe that any new technology designed to make
      minimal invasive surgery easier and more comfortable for the surgeon is most
      likely to have better and safer outcomes in the long run. Our only concern is its
      cost effectiveness and we believe that if the cost factor is removed more and
      more surgeons will use the technology and it will increase the spectrum and the
      reach of minimally invasive thoracic surgery. This article reviews worldwide
      experience with robotic thoracic surgery and addresses the potential benefits and
      limitations of using the robotic platform for the performance of thoracic
      surgical procedures. 

PMID- 25598602
TI  - Impact of laparoscopic experience on virtual robotic simulator dexterity.
AB  - BACKGROUND: Different skills are required for robotic surgery and laparoscopic
      surgery. We hypothesized that the laparoscopic experience would not affect the
      performance with the da Vinci((r)) system. A virtual robotic simulator was used
      to estimate the operator's robotic dexterity. MATERIALS AND METHODS: The
      performance of 11 surgical fellows with laparoscopic experience and 14 medical
      students were compared using the dV-trainer((r)). Each subject completed three
      virtual endo-wrist modules ("Pick and Place," "Peg Board," and "Match Board").
      Performance was recorded using a built-in scoring algorithm. RESULTS: In the Peg
      Board module, the performance of surgical fellows was better in terms of the
      number of instrument collisions and number of drops (P < 0.05). However, no
      significant differences were found in the percentage scores of the three endo
      wrist modules between the groups. CONCLUSION: Robotic dexterity was not
      significantly affected by laparoscopic experience in this study. Laparoscopic
      experience is not an important factor for learning robotic skills.

PMID- 25598603
TI  - Comparison of surgical, functional, and oncological outcomes of open and robot
      assisted partial nephrectomy.
AB  - BACKGROUND: We aimed to compare the surgical, oncological, and functional
      outcomes of robot-assisted partial nephrectomy (RAPN) with open partial
      nephrectomy (OPN) in the management of small renal masses. MATERIALS AND METHODS:
      Between 2009 and 2013, a total of 46 RAPN patients and 20 OPN patients was
      included in this study. Patients' demographics, mean operative time, estimated
      blood loss (EBL), warm ischemia time (WIT), length of hospital stay, pre- and
      post-operative renal functions, complications and oncological outcomes were
      recorded, prospectively. RESULTS: Mean tumor size was 4.04 cm in OPN group and
      3.56 cm in RAPN group (P = 0.27). Mean R.E.N.A.L nephrometry score was 6.35 in
      OPN group and 5.35 in RAPN group (P = 0.02). The mean operative time was 152 min
      in OPN group and 225 min in RAPN group (P = 0.006). The mean EBL in OPN and RAPN
      groups were 417 ml and 268 ml, respectively (P = 0.001). WIT in OPN group was
      significantly shorter than RAPN group (18.02 min vs. 23.33 min, P = 0.003). The
      mean drain removal time and the length of hospital stay were longer in OPN group.
      There were no significant differences in terms of renal functional outcomes and
      postoperative complications between groups. CONCLUSION: Minimally invasive
      surgical management of renal masses with RAPN offers better outcomes in terms of
      EBL and length of stay. However, the mean operative time and WIT were
      significantly shorter in OPN group. RAPN is a safe and effective minimally
      invasive alternative to OPN in terms of oncological and functional outcomes.

PMID- 25598604
TI  - Robotic-assisted laparoscopic partial nephrectomy: A single centre Indian
      experience.
AB  - BACKGROUND: We summarise our experience with RPN emphasising on learning curve,
      techniques and outcomes. PATIENTS AND METHODS: A retrospective chart review of 57
      patients was done. The preoperative workup included a triple phase CT
      angiography. The parameters analyzed were demographics, tumor characteristics,
      operative details, postoperative outcome, histopathology and follow-up. The data
      were compared with historical cohort of the laparoscopic partial nephrectomy
      (LPN). RESULTS: 58 renal units in 57 patients (45 males and 12 females) underwent
      RPN. The mean age was 53.08 +/- 13.6 (30-71) years. The mean tumor size was 4.96
      +/- 2.33 (2-15.5) cm. Average operative time was 129.4 +/- 29.9 (70-200) min.;
      mean warm ischemia time was 20.9 +/- 7.34 (9-39) min. 8 renal units in 7 patients
      were operated with the zero ischemia technique. The average follow-up was 5.15
      months (1-18). There was no recurrence. 15 patients underwent LPN. The mean tumor
      size was 4.3 +/- 1.6 (1.6-8) cm. operative time was 230.7 +/- 114.8 (150-300)
      min.; mean warm ischemia time was 31.8 +/- 9 min. The nephromerty score in the
      LPN group was 7.1 +/- 0.89, in the RPN group was 8.75 +/- 1.21. CONCLUSION: Our
      results suggest that prior experience of LPN shortens the learning curve for RPN
      as seen by shorter warm ischemia time and operative time in our series. The
      nephrometry score in RPN were higher suggesting that complex tumour can be
      managed with robotic approach.

PMID- 25598605
TI  - Robotic assisted laparoscopic adrenalectomy: Initial experience from a tertiary
      care centre in India.
AB  - INTRODUCTION: Laparoscopic adrenalectomy (LA) is now considered the standard for
      treatment of surgically correctable adrenal disorders. Robotic adrenalectomy has
      been performed worldwide and has established itself as safe, feasible and
      effective approach. We hereby present the first study in robotic transperitoneal
      LA from Indian subcontinent. MATERIALS AND METHODS: We conducted a retrospective
      evaluation of 25 patients who had undergone robotic assisted LA at a tertiary
      health centre by a single surgeon. Demographic, clinical, histopathological and
      perioperative outcome data were collected and analysed. RESULTS: Mean age of the
      patients was 45 years (range: 27-65 years). Eleven male and 14 female patients
      were operated. Mean operative time was 139 min +/- 30 min (range: 110-232 min)
      and mean blood loss was 85 ml +/- 12 ml (range: 34-313 ml). Mean hospital stay
      was 2.5 +/- 1.05 days (range: 2-6 days). Mean visual analogue scale score was 3.2
      (range: 1-6) mean analgesic requirement was 50 mg diclofenac daily (range: 0-150
      mg). Histopathological evaluation revealed 11 adenomas, eight phaeochromocytomas,
      two adrenocortical carcinomas, and four myelolipomas. According to Clavien-Dindo
      classification, three patients developed Grade I post-operative complications
      namely hypotension and pleural effusion. CONCLUSION: Robotic adrenalectomy is
      safe, technically feasible and comfortable to the surgeon. It is easier to
      perform with a short learning curve.

PMID- 25598606
TI  - Comparison of robotic surgery and laparoscopy to perform total hysterectomy with
      pelvic adhesions or large uterus.
AB  - BACKGROUND: Currently, benefits of robotic surgery in patients with benign
      gynecological conditions remain unclear. In this study, we compared the surgical
      outcome of robotic and laparoscopic total hysterectomies and evaluated the
      feasibility of robotic surgery in cases with pelvic adhesions or large uterus.
      MATERIALS AND METHODS: A total of 216 patients receiving total hysterectomy via
      robotic or laparoscopic approach were included in this study. Of all 216
      patients, 88 underwent robotic total hysterectomy and 128 underwent laparoscopic
      total hysterectomy. All cases were grouped by surgical type, adhesion score, and
      uterine weight to evaluate the interaction or individual effect to the surgical
      outcomes. The perioperative parameters, including operation time, blood loss,
      postoperative pain score, time to full diet resumption, length of hospital stay,
      conversion rate, and surgery-related complications were compared between the
      groups. RESULTS: Operation time and blood loss were affected by both surgical
      type and adhesion score. For cases with severe adhesions (adhesion score greater
      than 4), robotic surgery was associated with a shortened operation time (113.9 +/
      38.4 min versus 164.3 +/- 81.4 min, P = 0.007) and reduced blood loss (187.5 +/-
      148.7 mL versus 385.7 +/- 482.6, P=0.044) compared with laparoscopy. Moreover,
      robotic group showed a lower postoperative pain score than laparoscopic group, as
      the effect was found to be independent of adhesion score or uterine weight. The
      grade-II complication rate was also found to be lower in the robotic group.
      CONCLUSIONS: Comparing to laparoscopic approach, robotic surgery is a feasible
      and potential alternative for performing total hysterectomy with severe
      adhesions.

PMID- 25598608
TI  - Robotic surgery for rectosigmoid junction tumor with ovarian metastases.
AB  - Isolated ovarian metastases from colorectal cancer (CRC) are rare disease
      presenting in approximately 3% of all patients undergoing colorectal resection.
      Most reports describe an open approach to the disease, but we report a case
      isolated ovarian metastases from CRC managed completely by robotic technique. A
      54-year-old female, with a family history of CRC, was admitted for rectosigmoid
      junction cancer. Computed tomography scan demonstrated in rectosigmoid tumor and
      pelvic mass, presumed as teratoma. Robotic surgery discovered a 10-cm
      encapsulated tumor, attached to the left ovary, with no macroscopic peritoneal
      involvement. The pathologic diagnosis of the resected pelvic mass, ovarian
      metastases from CRC. Robotic anterior resection was performed. Operative time was
      lasted 165 min, considering 25 min for robotic system set up. This is the first
      report to describe robot-assisted anterior resection and oophorectomy in patient
      with isolated ovarian metastases from rectosigmoid junction cancer. 

PMID- 25598607
TI  - Robotic lobectomy: The first Indian report.
AB  - INTRODUCTION: Even today, open lobectomy involves significant morbidity. Video
      assisted thoracic surgery (VATS) lobectomy results in lesser blood loss, pain,
      and hospital stay compared to lobectomy by thoracotomy. Despite being an
      excellent procedure in expert hands, VATS lobectomy is associated with a longer
      learning curve because of its inherent basic limitations. The da Vinci surgical
      system was developed essentially to overcome these limitations. In this study, we
      report our initial experience with robotic pulmonary resections using the
      Completely Portal approach with four arms. To the best of our knowledge this is
      the first series of robotic lobectomy reported from India. MATERIAL AND METHODS:
      Data on patient characteristics, operative details, complications, and
      postoperative recovery were collected in a prospective manner for patients who
      underwent Robotic Lung resection at our institution between March 2012 and April
      2014 for various indications including both benign and malignant cases. RESULTS:
      Between March 2012 to April 2014, a total of 13 patients were taken up for
      Robotic Lobectomy with a median age of 57 years. The median operative time was
      210 min with a blood loss of 33 ml. R0 clearance was achieved in all patients
      with malignant disease. The median lymph node yield in nine patients with
      malignant disease was 19 (range 11-40). There was one intra-operative
      complication and two postoperative complications. The median hospital stay was 7
      days with median duration to chest tube removal being 3 days. CONCLUSION: Robotic
      lobectomy is feasible and safe. It appears to be oncologically sound surgical
      treatment for early-stage lung cancer. Comparable benefits over VATS needs to be
      further evaluated by long-term studies.

PMID- 25598610
TI  - Innovation in robotic surgery: the Indian scenario.
AB  - Robotics is the science. In scientific words a "Robot" is an electromechanical
      arm device with a computer interface, a combination of electrical, mechanical,
      and computer engineering. It is a mechanical arm that performs tasks in
      Industries, space exploration, and science. One such idea was to make an
      automated arm - A robot - In laparoscopy to control the telescope-camera unit
      electromechanically and then with a computer interface using voice control. It
      took us 5 long years from 2004 to bring it to the level of obtaining a patent.
      That was the birth of the Swarup Robotic Arm (SWARM) which is the first and the
      only Indian contribution in the field of robotics in laparoscopy as a total voice
      controlled camera holding robotic arm developed without any support by industry
      or research institutes. 

PMID- 25598609
TI  - Robotic excision of a pre-coccygeal nerve root tumor.
AB  - Pre-coccygeal ganglioneuroma is a rare clinical entity that presents incidentally
      or with non-specific symptoms. We present a case of a 25 year old housewife who
      was incidentally diagnosed with pre-coccygeal ganglioneuroma while getting
      investigated for primary infertility. The patient had no specific complaints
      except for irregular menstruation which had started 8 months back. Magnetic
      resonance imaging (MRI) was suggestive of a presacral and pre-coccygeal lesion.
      Resection of the tumor was done through the anterior approach using the da Vinci
      Si robotic system. Two robotic arms and one assistant port were used to
      completely excise the tumor. Robotic excision of such a tumor mass located at a
      relatively inaccessible area allows enhanced precision and 3-dimentional (3D)
      view avoiding damage to important surrounding structures. 

PMID- 25598611
TI  - The top species will no longer be humans: Robotic surgery could be a problem.

PMID- 25598612
TI  - Industrial hygiene: A global perspective.

PMID- 25598613
TI  - Post stapedotomy aviation: A changing scenario.
AB  - Aeromedical implications of stapedotomy like rapid barometric changes and G
      forces are generally thought to put an end to the aviation career of an aviator.
      Aviation industry has grown tremendously in the last few decades, and aviation
      now is not only occupational but also recreational. The Indian Military Aviation
      rules state that, "Stapedectomy cases will be assessed permanently unfit for
      flying duties. These cases will be cautioned against flying in an unpressurised
      aircraft." The basis of this is the aeromedical concerns associated with
      stapedotomy as clinical conditions which are of minor significance on the ground
      may become aggravated in the air. With an ever expanding civil and military
      aviation industry, the number of aviators who have undergone stapedotomy has also
      increased. Though grounding the aircrew is the safest option, but if medical
      certification is denied to all, then the majority who can fly safely will also be
      excluded, thus denying the organization of its trained resources. This paper
      discusses post otosclerosis and post stapedotomy aeromedical concerns, reviews
      existing literature concerning post stapedotomy aviation and various post
      stapedotomy aviation policies. 

PMID- 25598614
TI  - An epidemiologic study of occupational stress factors in Mumbai police personnel.
AB  - INTRODUCTION: Occupational stress is common to each and every organization at
      various levels of hierarchy. The police organization is no exception to this.
      Rather policing is widely recognized as more stressful than any other occupation,
      nature of work, irregular duty hours, and many more factors, which can trigger
      stress. The present study was done to highlight some of these stressful factors
      in Mumbai police. MATERIALS AND METHODS: Simple as well as systematic random
      sampling technique was adopted to get equal representation from each zone as well
      as region from Mumbai police. Occupational stress index (OSI) questionnaire was
      prepared, pilot tested, and validated for screening stress. RESULT: We screened
      276 policemen for occupational stress. Seventy-three percent of them were in the
      30-50 years age group, and most of them (49%) studied up to H.S.C. Ninety-one
      percent were married and 56% had reported duty hours 12-16 h/day. Seventy-one
      percent were addicted to any of the substance. After screening we found 73%
      moderately stressed, whereas 18% highly stressed policemen. Sociodemographic
      factors which were age group (50-58 years), duration of service in years (>25
      years), duration of duty hours (>16 h/day), addiction habits, and number of
      monthly holidays (no holiday). We found role ambiguity, under participation, role
      overload, strenuous working condition, and unprofitability as predominant scales
      in OSI. So prevention as well as management of stress in policemen is the
      necessity of the current situation. This stress can be managed at organizational
      level by adopting right techniques, whereas at individual level by habituating
      right behavior and attitude.

PMID- 25598615
TI  - Does occupational health nursing exist in India?
AB  - BACKGROUND: Occupational health services are important to develop healthy and
      productive work forces, which should be delivered through occupational health
      team. Occupational health nurse (OHN) is an important member of this team and is
      required to apply nursing principles in conserving the health of workers in
      occupational settings. PURPOSE: This article attempts to map the occupational
      health nursing courses in India and design competencies and curriculum for such a
      course. MATERIALS AND METHODS: Information through the Internet, printed
      journals, and perspectives of the key stakeholders were the principal sources of
      data. DISCUSSION: In India, there is a need to initiate a course on occupational
      health nursing to provide occupational health services for the organized and
      unorganized sector workforce. A certificate course for occupational health
      nursing for 3-4 months duration offered through contact session mode can be an
      opportune beginning. However, to cater employed nurses an online course can be
      another effective alternative. The theoretical part should essentially include
      modules on occupational diseases, industrial hygiene, and occupational health
      legislation, whereas the modules on practical aspects can include visits to
      industries. Taking into account the existing norms of Indian Factories Act for
      hazardous units of organized sector an estimated 1,34,640 OHNs are required.
      CONCLUSION: There is a need-supply gap in the number of occupational health
      nursing manpower in India, which can be attributed to the absence of any course
      to train such manpower.

PMID- 25598616
TI  - A study of respiratory function among the workers engaged in ginning processes.
AB  - BACKGROUND: Known respiratory health effects of exposure to cotton dust are
      mainly altered pulmonary function findings and symptom of chest tightness. A
      number of studies have been carried out all over the world to enumerate and
      evaluate the health effects of cotton dust exposed workers in different
      processes. However, such studies carried out in ginning industry especially in
      Indian context are scanty. OBJECTIVES: This study was initiated to explore
      occupational and morbidity details and respiratory functional status of the
      exposed workers as well as to investigate across the working shift pulmonary
      function changes. MATERIALS AND METHODS: A cross-sectional study was conducted
      including workers from ginning units where principal exposure is from cotton
      dust. All the workers of the selected ginning units were subjected to an
      interview with a predesigned questionnaire to collect occupational and medical
      history, clinical examination and pulmonary function test. RESULTS: In this
      present study, no cross-shift significant change in relation to PEFR and FEV1
      values is observed. However, chronic effect on lung function is observed in a few
      subjects and declining trend of values was observed with increasing job duration
      as well as age of workers and among smokers. Other health problems among these
      subjects were backache and joint pain. CONCLUSIONS: Studies on cotton textile
      workers have shown both cross-shift and chronic decline of values. In this study
      on ginning workers, chronic effect only is observed. This difference of
      observation may be explained by different nature of exposure in case of ginning.
      This study recommends regular periodic clinical examination, lung function test
      and monitoring of dust, gram-negative bacteria and endotoxins in such workplaces.

PMID- 25598617
TI  - A study of morbidity pattern among iron and steel workers from an industry in
      central India.
AB  - BACKGROUND: Iron is the world's most commonly used metal and can usually be found
      with other elements in the form of steel. In this era of machines, it is the
      inevitable part in production of various materials like eyeglass frames, jet
      aircraft, the space shuttle, automobiles, and surgical instruments. Occupational
      factors make an important contribution to the global burden of disease, but the
      reliable data on occupational disease are much more difficult to obtain. Hence,
      the current study was carried out to find out the morbidity pattern among iron
      and steel workers. MATERIALS AND METHODS: A cross-sectional study. was carried
      out after obtaining permission from Institutional Ethics Committee in an iron and
      steel factory. Worker's detailed information regarding profile was taken in
      pretested questionnaire format after obtaining the informed written consent and
      explaining the purpose of study. Workers were also interviewed regarding their
      years of job, job satisfaction, usage of protective devices, and history of
      injuries during work. Worker's detailed general and systemic examination was
      conducted. RESULTS: The overall prevalence of morbidities among the workers was
      60%. It was observed that commonest morbidity in the workers was lumbago
      (musculoskeletal pain), that is, 33.25%which was more in Group B (49.73%) than
      Group A (18.78%), followed by occupational dermatitis (27%) which more common in
      Group A (33.33%) than Group B (19.79%). It was seen that occupation-related
      morbidities were more prevalent in Group A, i.e. Exposed group (P < 0.001).
      CONCLUSION: It was observed that occupation-related morbidities were more common
      in exposed group (EG) than that of nonexposed group (NEG) and the difference was
      found to be statistically significant (P < 0.001).

PMID- 25598618
TI  - Physical and psychological work demands as potential risk factors for
      musculoskeletal disorders among workers in weaving operations.
AB  - AIM: The study was undertaken to examine the relationship between perceived
      physical and psychological work demands and self reported musculoskeletal
      disorders (MSDs) among workers involved in weaving operations. METHOD: The Nordic
      Musculoskeletal Disorders Questionnaire and Work Demands Scale, developed and
      standardized for the present investigation were the tools for data collection.
      Chi square test was used to assess univariate associations between work demands
      and reported MSDs. Multiple logistic regression analysis was performed for each
      of the outcome MSD retaining the variables in the model to adjust for potential
      confounding. RESULTS: Women were significantly more affected than men in
      shoulders, wrists/hands, upper back, lower back, and ankle/feet. Perceived
      physical and psychological demands were significantly associated with MSDs of
      different body regions. Pulling, pushing, moving, lifting and lowering heavy
      objects, working while bent or twisted at the waist, and repetitive motions with
      hands/wrists were the main physical factors retained in the regression models
      with odds ratios greater than 2. Conflicting demands, work is not remunerative,
      and no sufficient time to get the job done were the main psychological factors
      retained in the regression models with odds ratios greater than 1.68. Gender was
      found to be a significant factor for shoulders, wrists/hands, lower back, and
      ankles/feet with odds ratios ranging from 1.71 to 2.14. MSDs occurrence was more
      probable in the mentioned regions among women as compared to men. Both physical
      and psychological work demands in the work environment were contributing factors
      for developing MSDs among workers involved in weaving operations.

PMID- 25598619
TI  - Prevalence and pattern of occupational injuries at workplace among welders in
      coastal south India.
AB  - BACKGROUND: Injuries among welders are an important health issue in metal
      industries at global level. The study aimed to assess the prevalence and pattern
      of injuries and its possible associated risk factors among welders. MATERIALS AND
      METHODS: A cross-sectional study was conducted among 209 welders in metal
      industries of Puducherry, coastal south India. Data regarding all types of
      injuries during the past 1 year were collected by administering a pre-designed
      questionnaire. The various risk factors associated with injuries that include
      age, training before induction, experience, job duration, tobacco chewing,
      alcohol use and use of protective measures were assessed using standard
      questionnaire. The data was analyzed by univariate and multiple logistic
      regression analysis. RESULTS: Majority of subjects were aged between 20 and 40
      years (160, 76.6%) and educated below 10(th) standard (181, 86.6%). Mean number
      of injury was found to be 10.74 (SD = 5.74) in the preceding year. All of them
      had more than 2 injuries and 44% (92) of them had more than 10 injuries. All of
      them had abrasions and more than three fourths of them had each of lacerations,
      foreign body in the eye, flash burns and contusions. Multiple logistic regression
      analysis showed that age less than 30 years (OR = 5.19), tobacco use (OR = 2.56),
      alcohol use (OR = 3.96) and institutional training (OR = 0.10) were the
      predictors associated with more than 10 injuries among welders. CONCLUSION:
      Injury among welders is an important health problem in this area. Strategies for
      strengthening institutional training for younger age groups may help in
      decreasing the burden of injuries.

PMID- 25598620
TI  - Health profile of women ragpicker members of a nongovernmental organization in
      Mumbai, India.
AB  - BACKGROUND: In India, ragpickers form the base of hierarchy of informal sector of
      the solid waste management. Assessment of general and gender specific health of
      women is conducted in this study in view of dearth of published evidence.
      MATERIALS AND METHODS: An interventional study was conducted from October 2003 to
      April 2005 in Mumbai, at the field office of a nongovernmental organization
      working for women ragpickers. By the systematic random sampling 168 women
      ragpickers were selected. Both general and gender-specific health needs of this
      socially and occupationally marginalized group, including health seeking behavior
      were explored in this study. Fourteen participants were trained as health
      volunteers to create awareness in the local community. The data was analyzed by
      using SPSS version 11.0 software program (SPSS Inc., Chicago, Illinois, USA).
      RESULTS: Marriage at young age, multiple pregnancies, low preference toward
      temporary methods of contraception, high addiction were prevalent in this lower
      socioeconomic young workforce. Morbidity was statistically significant among
      ragpickers who collected rags along dumpsite than street side and door to door
      waste collectors (chi(2) = 27.8; df = 2; P < 0.001 significant). A need-based
      training program helped to improve knowledge of the participants [z = 12.7 (P <
      0.05)]. CONCLUSIONS: Unfulfilled health needs of this underprivileged workforce
      who contributes to the ecology and economy of the city need to be addressed.
      Sensitization of both general public and government is essential to legitimize
      this occupation. This in turn may help to alleviate poverty and environmental
      degradation; characteristic of rapid and unplanned urbanization in India.

PMID- 25598621
TI  - Perceived stress and stressors among house officers.
AB  - BACKGROUND: House officers training has always been regarded as a highly
      stressful environment to doctors. The objectives of our study were to assess
      perceived stress and sources of stress among house officers. MATERIALS AND
      METHODS: A cross-sectional questionnaire-based survey was carried out among house
      officers working in Civil Hospital, Karachi, Pakistan, and Jinnah Postgraduate
      Medical Centre, Karachi, Pakistan, during November and December, 2013. Perceived
      stress was assessed using perceived stress scale. A 15-item questionnaire was
      used to assess sources of stress and was graded by Likert scale (1 = very low, 5
      = very high). To calculate the difference of mean for stressors by gender of
      house officers, t-test with 95% confidence interval was used. RESULTS: The
      overall response rate was 81.5% (269 out of 330). One hundred twenty-nine (47.9%)
      were found to be under stress of whom 32 (24.8%) were males and 97 (75.2%) were
      females. Top five stressors reported by house officers were night calls,
      workload, time pressure, working alone, and coping with diagnostic uncertainty.
      Significant differences for stressors by gender were found for night calls (P <
      0.05), unrealistically high expectation by others (P < 0.05), financial issues (P
      < 0.05), and lack of senior support (P < 0.05). CONCLUSION: Majority of house
      officers working in Civil Hospital, Karachi, and Jinnah Postgraduate Medical
      Centre, Karachi, were under high level of stress. Therefore, immediate steps
      should be taken for control of stress and its management.

PMID- 25598622
TI  - Squamous cell carcinoma of the scrotum - still an occupational hazard.
AB  - Squamous cell carcinoma (SCC) of the scrotum was one of the first occupational
      diseases to be described, and acquired its eponym from Sir Percivall Pott. The
      condition has now become rare owing to the establishment of industrial health
      norms. A 45-year-old male with a history of long-term exposure to petrochemicals
      presented to our institution with a scrotal lesion and underwent wide-local
      excision of the same. Histopathology revealed well-differentiated SCC involving
      the epididymis. Treatment options included excision with ilio-inguinal bloc
      dissection (in the event of lymphadenopathy) with subsequent chemotherapy and/or
      radiotherapy. Tumors following occupational exposure thus continue to contribute
      to the rapidly decreasing incidence of scrotal carcinoma. 

PMID- 25598623
TI  - Job satisfaction, job stress and psychosomatic health problems in software
      professionals in India.
AB  - This questionnaire based study investigates correlation between job satisfaction,
      job stress and psychosomatic health in Indian software professionals. Also,
      examines how yoga practicing Indian software professionals cope up with stress
      and psychosomatic health problems. The sample consisted of yoga practicing and
      non-yoga practicing Indian software professionals working in India. The findings
      of this study have shown that there is significant correlation among job
      satisfaction, job stress and health. In Yoga practitioners job satisfaction is
      not significantly related to Psychosomatic health whereas in non-yoga group
      Psychosomatic Health symptoms showed significant relationship with Job
      satisfaction. 

PMID- 25598624
TI  - A comment on "Occupational hazard exposure and general health profile of welders
      in rural Delhi".

PMID- 25598625
TI  - Cadmium toxicity in silversmith: Safety is never too much!

PMID- 25598626
TI  - Occupational kidney disease: Is exposure to ammonium nitrate a risk factor?

PMID- 25598627
TI  - Review on Polygonum minus. Huds, a commonly used food additive in Southeast Asia.
AB  - Polygonum minus (Polygonaceae), generally known as 'kesum' in Malaysia is among
      the most commonly used food additive, flavoring agent and traditionally used to
      treat stomach and body aches. Raw or cooked leaves of P. minus are used in
      digestive disorders in the form of a decoction and the oil is used for dandruff.
      The pharmacological studies on P. minus have demonstrated antioxidant, in vitro
      LDL oxidation inhibition, antiulcer activity, analgesic activity, anti
      inflammatory activity, in vitro antiplatelet aggregation activity, antimicrobial
      activity, digestive enhancing property and cytotoxic activity. The spectroscopic
      studies of essential oil of P. minus showed the presence of about 69 compounds,
      which are responsible for the aroma. The phytochemical studies showed presence of
      flavonoids and essential oils. This review is an effort to update the botanical,
      phytochemical, pharmacological and toxicological data of the plant P. minus. 

PMID- 25598628
TI  - Minerals salt composition and secondary metabolites of Euphorbia hirta Linn., an
      antihyperglycemic plant.
AB  - Phytochemical study and research on acute toxicity were performed on the aerial
      parts (leaves and stems) of Euphorbia hirta Linn. The phytochemical screening and
      chromatography revealed the presence of saponin, sterol, terpene, alkaloids,
      polyphenols, tannins and flavonoids and especially mucilage. The evaluation of
      total polyphenols and total flavonoids gave 120.97 +/- 7.07 gallic acid
      equivalents (GAE) mg/g (mg of GAE/g of extract) of dry extract and 41.4 +/- 0.5
      mg quercetin equivalent per gram (QE/g) (mg of QE/g of plant extract) of dry
      extract respectively. The physicochemical study revealed moisture content of
      7.73% +/- 0.00%, total ash 7.48% +/- 0.03%. Sulfuric ash 9.05% +/- 0.01%,
      hydrochloric acid insoluble ash of 0.8% +/- 0.02%. The search for minerals salt
      revealed the presence of Cr, Zn, K, Ca and Mg having an important role in glucose
      metabolism. The acute toxicity study showed that the toxic dose may be above 3000
      mg/kg. The results of these studies indicate that extracts from the leaves and
      stem of E. hirta Linn. contains trace elements and minerals salt and bioactive
      secondary metabolites which explain their therapeutic uses for treating diabetes
      mellitus. 

PMID- 25598629
TI  - Chemical Constituents from the Leaves of Euphorbia ammak Growing in Saudi Arabia.
AB  - Investigation of the chloroform extract of Euphorbia ammak leaves led to the
      isolation of three compounds: euphol (1), alpha-glutinol (2) and stigmasterol (3)
      Their structures were elucidated by 1D and 2D NMR, as well as by comparison with
      the reported data. Compounds 1-3 exhibited cytotoxicity in vitro against human
      cervical adenocarcinoma (Hela), among which, compound 1 showed the best activity.

PMID- 25598630
TI  - Evaluation of anti-inflammatory activity of methanolic extract of leaves of
      Bougainvillea spectabilis in experimental animal models.
AB  - BACKGROUND: Bougainvillea spectabilis (BS) (family Nyctaginaceae) is said to
      possess hypoglycemic and anti-inflammatory activities in experimental animals. We
      had set forward to examine the potential anti-inflammatory activities of BS in
      experimental models of inflammation. MATERIALS AND METHODS: Fresh dried leaves
      from the flowering plant of BS were collected from the local area during the
      flowering season and air dried (215.00 g). Methanol was extracted, and the
      solvent was removed on a rotary evaporator under reduced pressure. The extract
      was freeze-dried (lyophilized) and the yield was 8 g. This was used as an
      emulsion prepared in propylene glycol and orally administered (20 and 50 mg/kg).
      Acute anti-inflammatory activity of BS was evaluated using carrageenan and
      dextran whereas chronic anti-inflammatory (immunoregulatory) activity was
      evaluated by Freund's adjuvant-induced arthritis model. RESULTS: BS (20 mg/kg and
      50 mg/kg) had shown significant anti-inflammatory effects 20.6% and 67.6%,
      respectively, on carrageenan-induced acute inflammatory models. In dextran
      induced edema, the effect was 30% and 66%, respectively. The standard drug
      indomethacin (87.3% and 91.5%, respectively) showed better inhibitory response in
      both models. In arthritic model 50 mg/kg of BS showed significant chronic anti
      inflammatory effect (38.46%) in comparison to the standard drug dexamethasone
      (84.6%). CONCLUSION: Our data indicate that the methanol extract of BS (50 mg/kg)
      leaves has significant anti-inflammatory and immunoregulatory activity. Further
      studies involving isolation of active principles will help to pinpoint the
      mechanisms contributing to the observed activities of BS.

PMID- 25598631
TI  - A novel reverse phase high-performance liquid chromatography method for
      standardization of Orthosiphon stamineus leaf extracts.
AB  - BACKGROUND: Orthosiphon stamineus Benth. (Lamiaceae) is a traditional medicinal
      plant which has been used in treating various ailments such as kidney diseases,
      bladder inflammation, arthritis and diabetes. The leaves contain high
      concentration of phenolic compounds, thus, rosmarinic acid (RA), 3'-hydroxy-5, 6,
      7, 4'-tetramethoxyflavone (TMF), sinensetin (SIN) and eupatorin (EUP) were chosen
      as a marker compounds for standardization of various O. stamineus leaf extracts.
      OBJECTIVE: The aim was to develop and validate a new high-performance liquid
      chromatography (HPLC) method for quantification of 4 marker compounds (RA, TMF,
      SIN, EUP) in various O. stamineus leaf extracts. MATERIALS AND METHODS: The
      method was developed and validated using RP-HPLC-diode-array detection at 320 nm
      for accuracy, precision and limits of detection and was applied for
      quantification of it markers in five different extracts prepared in solvents with
      increasing polarity, using a gradient mobile phase 0.1% formic acid: Acetonitrile
      at a flow rate of 1 ml/min on reverse phase acclaim polar advantage II C18 column
      (3 MUm, 3 * 150 mm) with 18 min separation time. RESULTS: The developed method
      provided satisfactory precision, and the accuracy of this method was in the range
      of 90.2% to 105.5%. All of 4 compounds showed good linearity at R2 > 0.999.
      CONCLUSION: The developed method is a simple, cost effective with shorter run
      time (18 min) in comparison to previous methods (30 min) and utilization of
      environmental-friendly solvents system. Therefore, this method has the potential
      to replace currently used methods in the routine standardization work of O.
      stamineus extracts, raw materials and its commercial products.

PMID- 25598632
TI  - Analysis of L-citrulline and L-arginine in Ficus deltoidea leaf extracts by
      reverse phase high performance liquid chromatography.
AB  - BACKGROUND: Ficus deltoidea (FD) is one of the native plants widely distributed
      in several countries in Southeast Asia. Previous studies have shown that FD leaf
      possess antinociceptive, wound healing and antioxidant properties. These
      beneficial effects have been attributed to the presence of primary and secondary
      metabolites such as polyphenols, amino acids and flavonoids. OBJECTIVE: The aim
      was to develop a reverse phase high-performance liquid chromatography method with
      ultraviolet detection that involves precolumn derivatisation with O-phthaladehyde
      for simultaneous analysis of two amino acids L-citrulline and L-arginine in FD
      leaf extracts. MATERIALS AND METHODS: An isocratic elution program consisting of
      methanol: acetonitrile: Water at 45:45:10 v/v (solvent A) and 0.1 M phosphate
      buffer pH 7.5 (solvent B) at A: B v/v ratio of 80:20 on Zorbax Eclipse C18 SB-Aq
      column (250 * 4.6 mm, 5 MUm) were used. The flow rate was set at 1 ml/min and
      detection was carried out at 338 nm with 30 min separation time. RESULTS: Good
      linearity for L-citrulline and L-arginine was obtained in the range 0.1-1000
      MUg/ml at R (2) >= 0.998. The limit of detection and limit of quantification
      values for both L-citrulline and L-arginine were 1 and 5 MUg/ml, respectively.
      The average of recoveries was in the range 94.94-101.95%, with relative standard
      deviation (%RSD) less than 3%. Intra- and inter-day precision was in the range
      96.36-102.43% with RSD less than 2%. CONCLUSION: All validation parameters of the
      developed method indicate the method is reliable and efficient for simultaneous
      determination of L-citrulline and L-arginine for routine analysis of FD.

PMID- 25598633
TI  - Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley
      rats.
AB  - BACKGROUND: Swietenia macrophylla King. (Meliaceae) seeds (SMS); commonly known
      as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in
      traditional Malay medicine for the treatment of diabetes and hypertension. The
      people eat only a tiny amount of raw seed, weighing not more than 5 mg. AIM: To
      evaluate the safety of Swietenia macrophylla seeds (SMS) at a single-dose oral
      administration of 2 g/kg body weight (bw) in sprague dawley (SD) rats. MATERIALS
      AND METHODS: Eight-week old male and female SD rats were administered a single
      oral dose of 2g/kg bw. The rats' general behavior, and toxic signs were observed
      throughout the 14-day study period. The food and water intake by rats and their
      body weight were monitored during the study period. At the end of the study
      period, the relative weights of the organs (lung, liver, spleen, heart, kidney,
      testis, stomach); the hematological and biochemical parameters were measured; the
      architecture and histology of the organs (liver, kidney and lungs) were observed.
      RESULTS: Oral administration of SMS to rats did not affect, either food or water
      intake; relative organ weight of vital organs; the hematological and biochemical
      parameters; did not show significant changes in the architecture and histology of
      vital organs. Overall, there were neither signs of toxicity nor deaths recorded
      during the study period. CONCLUSION: The rat dose of 2 g/kg bw is equivalent to
      the human dose of 325 mg/kg bw, which is well below the usual amount consumed by
      people, did not show any signs of toxicity in rats.

PMID- 25598634
TI  - Cycloolivil, a lignan from the roots of Stereospermum suaveolens.
AB  - BACKGROUND: Stereospermum suaveolens DC. (Syn. S. chelonoides) belonging to
      family Bignoniaceae is an important medicinal plant in India. Traditionally, it
      is mainly used as analgesic, liver stimulant, astringent, wound healing and
      antidyspeptic. Roots of this plant are one of the ingredients of Dashamularishta.
      The plant has been studied for many pharmacological actions, only few were
      concerned with isolation of active compounds. OBJECTIVE: The present work deals
      with the isolation and identification of phytochemical constituents present in
      the roots of Stereospermum suaveolens. MATERIAL AND METHODS: The compounds were
      isolated from the ethyl acetate-soluble fraction from the methanol extract of S.
      suaveolens by using open silica gel column chromatography and HPLC was carried
      out for all the fractions to target the major peaks in fractions. RESULTS AND
      CONCLUSION: The isolated compounds structures were elucidated by analysis of
      spectroscopic data (UV, IR, 1D-NMR, and MS) and characterized as Cycloolivil (1)
      reported for the first time from this plant species, Lapachol (2) and beta
      sitosterol (3), respectively.

PMID- 25598636
TI  - The optimization of essential oils supercritical CO2 extraction from Lavandula
      hybrida through static-dynamic steps procedure and semi-continuous technique
      using response surface method.
AB  - AIM: The aim of this study was to examine and evaluate crucial variables in
      essential oils extraction process from Lavandula hybrida through static-dynamic
      and semi-continuous techniques using response surface method. MATERIALS AND
      METHODS: Essential oil components were extracted from Lavandula hybrida
      (Lavandin) flowers using supercritical carbon dioxide via static-dynamic steps
      (SDS) procedure, and semi-continuous (SC) technique. RESULTS: Using response
      surface method the optimum extraction yield (4.768%) was obtained via SDS at
      108.7 bar, 48.5 degrees C, 120 min (static: 8*15), 24 min (dynamic: 8*3 min) in
      contrast to the 4.620% extraction yield for the SC at 111.6 bar, 49.2 degrees C,
      14 min (static), 121.1 min (dynamic). CONCLUSION: The results indicated that a
      substantial reduction (81.56%) solvent usage (kg CO2/g oil) is observed in the
      SDS method versus the conventional SC method.

PMID- 25598635
TI  - In vitro free radical scavenging and antioxidant properties of ethanol extract of
      Terminalia glaucescens.
AB  - BACKGROUND: Reactive oxygen species (ROS) are implicated in various pathological
      conditions. Synthetic antioxidants have adverse health effects, while many
      medicinal plants have antioxidant components that can prevent the harmful effects
      of ROS. OBJECTIVES: This study quantitatively determined the total phenolic
      content (TPC), total flavonoid content (TFC), and antioxidant properties of
      ethanol extract of the stem bark of Terminalia glaucescens (EESTG). MATERIALS AND
      METHODS: The objectives were achieved based on in vitro assays. Data were
      analyzed by Sigma Plot (version 11.0). RESULTS: Using gallic acid as the standard
      compound, TPC value obtained was 596.57 MUg GAE/mg extract. TFC content of EESTG,
      determined as quercetin equivalent was 129.58 MUg QE/mg extract. Furthermore,
      EESTG significantly (P < 0.001) displayed higher reducing power activity than the
      standard compounds (ascorbic acid and butylated hydroxytoluene [BHT]). Total
      antioxidant capacity assay, measured by phosphomolybdate method, was 358.33 +/-
      5.77 MUg butylated hydroxytoluene equivalents [BHTE]/mg extract. beta-carotene
      linoleate bleaching method affirmed the potency of EESTG because of its
      significantly (P < 0.001) higher anti-oxidant activity when compared with
      quercetin and BHT. Based on DPPH assay, EESTG displayed significantly (P < 0.001)
      higher activity than BHT, while the hydroxyl radical scavenging activities of BHT
      and quercetin significantly (P < 0.001) exceeded that of the extract, although
      EESTG still displayed a high level of activity obtained as 83.77% in comparison
      to 92.80% of the standard compounds. CONCLUSION: Findings from this study
      indicate the presence of promisingly potent phytoconstituents in EESTG that have
      the capability to act as antioxidants and free radical scavengers.

PMID- 25598637
TI  - Evaluation of antitumor activity and antioxidant status of Alternanthera
      brasiliana against Ehrlich ascites carcinoma in Swiss albino mice.
AB  - OBJECTIVE: The main objective of the present study was to explore the antitumor
      activity of the ethyl acetate extract of the Alternanthera brasiliana (EAAB) and
      its antioxidant status against Ehrlich ascites carcinoma (EAC) in Swiss albino
      mice. MATERIALS AND METHODS: Based on the preliminary in vitro cytotoxicity
      studies, EAAB was selected for anti-tumor and antioxidant effects. Anticancer
      activity of EAAB was evaluated against EAC in Swiss albino mice at the doses of
      200 and 400 mg/kg. EAAB was administered for 14 consecutive days after induction
      of cancer. After 24 h of the last dose and 18 h of fasting, half of the mice were
      sacrificed and rest were kept alive for assessing any increase in life span. The
      antitumor effect of EAAB was assessed by evaluating tumor volume, viable and
      nonviable tumor cell count, tumor weight, hematological and biochemical
      parameters of EAC bearing host. Furthermore, the antioxidant and
      histopathological parameters were evaluated. RESULTS: EAAB treatment has shown
      significant decrease in tumor volume, viable cell count, tumor weight and
      elevated the life span of EAC tumor bearing mice in a dose dependent manner. In
      hematological profile count of RBC, hemoglobin, and WBC were found reverted to
      normal. EAAB also significantly decreased the levels of lipid peroxidation and
      significantly increased the levels of GSH, SOD and Catalase. CONCLUSION: From the
      above results it may be concluded that EAAB has potent dose dependent antitumor
      activity and is comparable to that of 5-flourouracil.

PMID- 25598638
TI  - Chemical composition and antimicrobial activity of essential oils of Juniperus
      excelsa Bieb. (Cupressaceae) grown in R. Macedonia.
AB  - BACKGROUND: There are no information of the yield, chemical composition and
      antimicrobial activity of essential oils of berries (EOB) or leaves (EOL) of
      Juniperus excelsa Bieb. (Cupressaceae) growing wild in R. Macedonia. MATERIALS
      AND METHODS: Plant material was collected from two localities during two seasons.
      Essential oil composition was analyzed by gas chromatography/flame ionization
      detector/mass spectrometry (GC/FID/MS) and antimicrobial screening was made by
      disc diffusion and broth dilution method. RESULTS AND DISCUSSION: EOB yield
      ranged from 1.6-9.4 ml/kg and from 8.9-13.9 ml/kg for EOL. Two chemotypes of
      essential oil were differentiated, alpha-pinene-type (with 70.81% alpha-pinene in
      EOB and 33.83% in EOL), also containing limonene, beta-pinene and beta-myrcene
      while the sabinene-type (with 58.85-62.58% sabinene in EOB and 28.52-29.49% in
      EOL), was rich in alpha-pinene, beta-myrcene, limonene, cis-thujone, terpinolene
      and alpha-thujene. The most sensitive bacteria to the antimicrobial activity of
      EOB was Haemophilus influenzae (MIC = 31 MUl/ml). EOL have showed high activity
      towards: Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae
      (MIC = 125 MUl/ml). The pinene-type of essential oil showed moderate activity
      against Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus
      agalactiae, Streptococcus pyogenes, Corynebacterium spp. and Campylobacter jejuni
      (MIC >50%). The sabinene-type of the oil showed moderate activity to
      Streptococcus pyogenes, Haemopilus influenzae, Campylobacter jejuni and
      Escherichia coli (MIC >50%). No activity was observed toward Candida albicans.
      CONCLUSION: The analysis of EOB and EOL revealed two chemotypes (alpha-pinene and
      sabinene type) clearly depended on the geographical origin of the Macedonian
      Juniperus excelsa which also affected the antimicrobial activity of these oils.

PMID- 25598639
TI  - Evaluation of Bacillus cereus and Bacillus pumilus metabolites for anthelmintic
      activity.
AB  - OBJECTIVE: To assess the anthelmintic acivity of Bacillus cereus and Bacillus
      pumilus metabolites. MATERIALS AND METHODS: The successive solvent extractions
      with petroleum ether, ethyl acetate and methanol. The solvent extracts were
      tested for anthelmintic activity against Pheretima posthuma at 20 mg/ml
      concentration. The time of paralysis and time of death of the worms was
      determined for all the extracts. Albendazole was taken as a standard reference
      and sterile water as a control. RESULTS: All the sample extracts showed
      significant anthelmintic activity in paralyzing the worms comparable with that of
      the standard drug. The time of death exhibited by BP metabolites was close to the
      time exhibited by standard. CONCLUSION: The study indicates both bacteria
      Bacillus cereus and Bacillus pumilus have anthelmintic activity indicating
      potential metabolites in them.

PMID- 25598640
TI  - Effect of Butea monosperma leaf extracts on cyclophosphamide induced
      clastogenicity and oxidative stress in mice.
AB  - BACKGROUND: Butea monosperma is a medium sized deciduous tree of family Fabaceae.
      It is widely used by rural people in India to cure many disorders. It possesses
      antioxidant and anticancer activity which is a prerequisite for anticlastogenic
      activity. OBJECTIVE: To evaluate the effect of Butea monosperma leaf extracts on
      cyclophosphamide induced clastogenicity and oxidative stress in mice. MATERIALS
      AND METHODS: The present study assessed the role of aqueous and ethanolic leaf
      extracts of B. monosperma (AQEBM and ETEBM) on cyclophosphamide (CP) induced
      oxidative stress and DNA damage in mice using micronucleus assay for
      anticlastogenic activity and biochemical estimation of malondialdehyde (MDA) and
      glutathione (GSH) for antioxidant activity. The frequency of the micronucleated
      erythrocytes and mitotic index was studied in peripheral blood and bone marrow
      after 24 and 48 h of clastogenic exposure. RESULTS: CP treatment led to a
      significant (P < 0.001) increase in the frequency of micronuclei and decrease in
      the mitotic index (MI) in bone marrow and peripheral blood cells. Moreover, CP
      also significantly increased the lipid peroxidation as evidenced by an increase
      in the MDA content and decreased the antioxidant enzyme (GSH) in mice liver.
      Pretreatment with AQEBM and ETEBM reduced the frequency of micronuclei and
      increased the MI in the bone marrow and peripheral blood cells and also restored
      the MDA and GSH levels in mice liver. CONCLUSION: The AQEBM and ETEBM do contain
      compounds capable of inhibiting the CP induced oxidative stress and subsequent
      DNA damage in both the peripheral blood and bone marrow cells in mice.

PMID- 25598641
TI  - Anti-diabetic effects of ethanol extract of Bryonia laciniosa seeds and its
      saponins rich fraction in neonatally streptozotocin-induced diabetic rats.
AB  - CONTEXT: Bryonia laciniosa Linn. (Cucurbitaceae) seed is used in traditional
      medicine for a number of ailments including metabolic disorders. AIM: This study
      evaluated the anti-diabetic action of the ethanol extract of B. laciniosa seeds
      and saponin fraction of it through its effect on hyperglycemia, dyslipidaemia and
      oxidative stress in neonatally streptozotocin (n-STZ)-induced diabetic rats (n
      STZ diabetic rats). MATERIALS AND METHODS: Ethanol extract (250 and 500 mg/kg;
      p.o.), saponin fraction (100 and 200 mg/kg; p.o.) and standard drug glibenclamide
      (3 mg/kg; p.o.) were administered to diabetic rats when the rats were 6 weeks old
      and continued for 10 consecutive weeks. Effects of ethanol extract and saponin
      fraction on various biochemical parameters were studied in diabetic rats.
      RESULTS: The treatment with ethanol extract and saponin fraction for 10 weeks
      decrease in the levels of glucose, triglycerides, cholesterol, high-density
      lipoprotein, low-density lipoprotein, very low-density lipoprotein, serum urea,
      serum creatinine and diminished activities of aspartate transaminase, and alanine
      transaminase. The anti-hyperglycemic nature of B. laciniosa is probably brought
      about by the extra- the pancreatic mechanism as evidenced from unchanged levels
      of plasma insulin. B. laciniosa modulated effect of diabetes on the liver
      malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and
      catalase (CAT) activity. Administration of ethanol extract and saponin fraction
      to diabetic rats showed a significant reversal of disturbed antioxidant status.
      Significant increase in SOD, CAT, and levels of GSH was observed in treated n-STZ
      diabetic rats. CONCLUSION: The present study reveals the efficacy of B. laciniosa
      seed extract and its saponin fraction in the amelioration of n-STZ diabetic rats.

PMID- 25598642
TI  - In vitro antioxidant and free radical scavenging activity of four Alkanna species
      growing in Iran.
AB  - BACKGROUND: Medicinal plants are recognized as sources of natural antioxidants
      that can protect biological system from oxidative stress. OBJECTIVE: In this
      study, the antioxidant activities of four species of the Alkanna genus (Alkanna
      bracteosa, Alkanna frigida, Alkanna orientalis and Alkanna tricophila) were
      evaluated. MATERIALS AND METHODS: The dried roots of plant samples (100 g) were
      extracted separately by percolation method with MeOH/H2O (80/20) and four
      fractions were provided respectively with hexane, chloroform, ethyl acetate,
      butanol and water. Antioxidant activities were investigated by using 1,1-diphenyl
      2-picrylhydrazyl, ferric thiocyanate and thiobarbituric acid methods and compared
      with quercetin (as positive control). RESULTS: The results indicated that the
      butanol fractions of four species had the highest antioxidant activity and
      radical scavenging activity compared with the other fractions studied (P < 0.05).
      The 50% effective concentration (half - effective doses) values of butanol
      fractions are less than quercetin and other fractions, so, these fractions showed
      potent antioxidant activity. This indicated that the active compounds in the root
      parts of Alkanna species dissolved in the butanol. All the fractions of four
      species of Alkanna had antioxidant activity, while, there were no significant
      differences (P > 0.05) between the total antioxidant activities of same
      fractions. The total antioxidant activity values of Alkanna fractions in a
      descending order are as follows: Butanol fraction > ethyl acetate fraction >
      total extract > hexane fraction > chloroform fraction > aqueous fraction.
      CONCLUSION: The antioxidant activities of butanol fractions of samples were
      higher than quercetin. This may be because most of the active compounds of
      Alkanna species dissolved in the butanol.

PMID- 25598643
TI  - Anti-quorum sensing potential of Adenanthera pavonina.
AB  - BACKGROUND: Quorum sensing (QS) in Pseudomonas aeruginosa plays a key role in
      virulence factor production, biofilm formation and antimicrobial resistance.
      Because of emerging antimicrobial resistance in P. aeruginosa, there is a need to
      find an alternate nonantibiotic agent for the control of infections caused by
      this organism. OBJECTIVE: To evaluate anti-QS activity of Adenanthera pavonina
      L., a medicinal plant used in traditional medicine. MATERIALS AND METHODS:
      Preliminary screening for anti-QS activity of ethanol extract of A. pavonina was
      carried out using Chromobacterium violaceum CV026 biosensor strain and inhibition
      of QS-regulated violacein production was quantified using C. violaceum ATCC12472.
      Bioassay guided fractionation of ethanol extract resulted in ethyl acetate
      fraction (AEF) with strong anti-QS activity and AEF was evaluated for inhibition
      of QS-regulated pyocyanin production, proteolytic, elastolytic activity, swarming
      motility and biofilm formation in P. aeruginosa PAO1. RESULTS: AEF, at 0.5 mg/ml,
      inhibited pyocyanin production completely and at 1 mg/ml of AEF, complete
      inhibition of proteolytic and elastolytic activities were observed. However,
      viability of P. aeruginosa PAO1 was not affected at the tested concentrations of
      AEF as observed by cell count. Swarming motility was inhibited at the
      concentration of 0.1 mg/ml of AEF. Thin layer chromatography and biosensor
      overlay of AEF showed violacein inhibition zone at Rf value 0.63. CONCLUSION:
      From the results of this study, it can be concluded that A. pavonina extracts can
      be used as effective anti-QS agents.

PMID- 25598644
TI  - GC-MS analysis of bioactive compounds in the methanol extract of Clerodendrum
      viscosum leaves.
AB  - BACKGROUND: Clerodendrum viscosum is commonly found in India and Bangladesh.
      Previously, various parts of this plant were reported for treatment of different
      types of diseases and there was no report on GC-Ms analysis. OBJECTIVE: To
      analyze and characterize the phytochemical compounds of methanol extract of
      Clerodendrum viscosum using GC-MS. MATERIALS AND METHODS: The preliminary
      phytochemical screening of methanol extract was carried out according to standard
      procedures described in WHO guidelines. Various bioactive compounds of the
      extract were determined by GC-MS technique. RESULTS: The presence of steroids,
      triterpenoids, alkaloids, saponins, flavonoids, tannins and carbohydrate was
      found on phytochemical screening of methanol extract of the leaves. The GC-MS
      analysis showed 16 peaks of different phytoconstituents namely acetamide, N, N
      carbonylbis-, 4-Pyranone,2,3-dihydro-, alpha-D-Galactofuranoside, methyl 2,3,5,6
      tetra-O-methyl-, Glycerin, Xylitol, N, N-Dimethylglycine, 4H-Pyran-4-one,2,3
      dihydro-3, 5-dihydroxy-6-methyl-, Benzofuran,2,3-dihydro-, 5
      Hydroxymethylfurfural, 2(1H)Pyrimidinone,1-methyl-, 2,4-Dihydroxy-5,6
      dimethylpyrimidine, 3-Deoxy-d-mannoic lactone, 1,3-Methylene-d-arabitol, Orcinol,
      n-Hexadecanoic acid and Phenol,4,4'-(1-methyl ethylidene) bis etc. CONCLUSION:
      The bioactive compounds present in the methanol extract of Clerodendrum viscosum
      suggest the application of this extract for the treatment of various diseases by
      the aborigine tribes.

PMID- 25598646
TI  - Isolation, structural characterization and in silico drug-like properties
      prediction of a natural compound from the ethanolic extract of Cayratia trifolia
      (L.).
AB  - BACKGROUND: Natural products have continually played an important role in drug
      discovery because it serves as active principles in drugs as well as templates
      for synthesis of new drugs. Cayratia trifolia (L.) is a medicinal plant, which
      has been reported to have antiviral, antibacterial, antiprotozoal, hypoglycemic,
      anticancer and diuretic activities. OBJECTIVE: Therefore, the objective of this
      study is to isolate and identify the natural compound from the ethanolic extract
      of Cayratia trifolia (L.) and to predict the Absorption, Distribution, Metabolism
      and Excretion (ADME) properties of isolated natural compound. MATERIALS AND
      METHODS: Column chromatography and thin layer chromatography were used to isolate
      the natural compound and Fourier-transform infrared (FTIR) spectroscopy was used
      to predict the functional groups present in the isolated natural compound. The
      structural characterization studies were functionally carried out using (1)H,
      (13)C, two-dimensional nuclear magnetic resonance (NMR) and mass spectrometry
      methods. RESULTS: FTIR showed that, the groups of OH, C-H, C = C may be present
      in the isolated natural compound. (1)H, (13)C, two-dimensional NMR and mass
      spectrometry data suggests that the isolated natural compound probably like
      linoleic acid. In silico ADME properties, prediction of the compound was under
      acceptable range. CONCLUSION: Based on the results, it can be concluded that, the
      isolated natural compound of linoleic acid that has been exhibited good medicinal
      properties.

PMID- 25598647
TI  - Evaluation of analgesic, antipyretic and anti-inflammatory activity on Cordia
      dichotoma G. Forst. Leaf.
AB  - BACKGROUND: Cordia dichotoma G. Forst. is an important medicinal plant of family
      Boraginaceae. Traditionally, its leaves are used to treat fever, headache, and
      joint pain but its medicinal activities have not been proven by research.
      OBJECTIVE: To evaluate the analgesic, anti-inflammatory, and antipyretic activity
      of C. dichotoma G. Forst. leaf extract. MATERIAL AND METHODS: The various
      extracts of leaf powder were prepared by using soxhlet apparatus. The methanol
      extract was selected for pharmacological study. To evaluate analgesic activity,
      Eddy's hot plate method, to study anti-inflammatory activity, carageenan-induced
      rat paw edema method, and to study antipyretic activity, yeast-induced pyrexia
      method was used. SD female rats (180-200 g) were used for the study. RESULTS: In
      all three tests, the methanol extract high dose (400 mg/kg) was found to be
      highly significant as compared to standard drug. CONCLUSION: This study proved
      the traditional uses of plant leaves and concluded the analgesic, anti
      inflammatory, and antipyretic activity of the leaf methanol extract.

PMID- 25598648
TI  - Global Tobacco Control: An integrated approach to global health policy.
AB  - Following the development discussion in the last volume on the 'politics of
      health', Jennifer Prah Ruger argues that the Framework Convention on Tobacco
      Control (FCTC) represents a shift in global health policy that recognizes the
      importance of addressing health needs on multiple fronts and integrating public
      policies into a comprehensive set of health improvement strategies. She argues
      that the FCTC provides a model for multifaceted approaches to health improvement
      that require simultaneous progress on various dimensions.

PMID- 25598645
TI  - Antioxidant activities of ficus glomerata (moraceae) leaf gall extracts.
AB  - An excess production or decreased scavenging of reactive oxygen species (ROS) has
      been implicated in the pathogenesis of diverse metabolic disorders such as
      diabetes, cancer, atherosclerosis and neurodegeneration. Hence the antioxidant
      therapy has gained an utmost importance in the treatment of such diseases linked
      to free radicals. The medicinal properties of plants have been investigated and
      explored for their potent antioxidant activities to counteract metabolic
      disorders. This research highlights the chemical composition and antioxidant
      potential of leaf gall extracts (aqueous and methanol) of Ficus glomerata (F.
      glomerata), which is extensively used in the preparation of traditional
      medications to treat various metabolic diseases. The presences of phenolics,
      flavonoids, phytosterols, terpenoids and reducing sugars were identified in both
      the extracts. In comparison to the aqueous extract, the methanol extract had the
      highest total phenolic and flavonoid content at 370 +/- 3.2 mg of gallic acid
      equivalent per gram of dry weight (mg GAE/g dw) and 155 +/- 3.2 mg of quercetin
      equivalent per gram of dry weight (mg QUE/g dw), respectively. The antioxidant
      activities of leaf gall extracts were examined using diphenylpicrylhydrazyl
      (DPPH), Nitric oxide scavenging, hydroxyl scavenging and ferric reducing power
      (FRAP) methods. In all the methods, the methanolic extract showed higher
      antioxidant potential than the aqueous extract. A higher content of both total
      phenolics and flavonoids were found in the methanolic extract and the
      significantly high antioxidant activity can be positively correlated to the high
      content of total polyphenols/flavonoids of the methanol extract. The results of
      this study confirm the folklore use of F. glomerata leaf gall extracts as a
      natural antioxidant and justify its ethnobotanical use. Further, the results of
      antioxidant properties encourage the use of F. glomerata leaf gall extracts for
      medicinal health, functional food and nutraceuticals applications. Future work
      will be interesting in knowing the chemical composition and better understand the
      mechanism of action of the antioxidants present for development as drug for its
      therapeutic application. 

PMID- 25598649
TI  - Peer Status Among Incarcerated Female Offenders: Associations With Social
      Behavior and Adjustment.
AB  - Peers are a powerful socializing force, especially during adolescence. Whether
      peer status holds the same meaning, correlates, and consequences for female
      offenders remains unknown. Using a peer nomination technique in a sample of
      incarcerated females (N = 86, age 15-24 years), our study is the first to examine
      the association between peer status and psychopathology in a correctional
      facility. Results indicated that a key indicator of likeability was prosocial
      behavior; popularity was related to leadership; and social impact was associated
      with aggression. Popularity might serve as a buffer against, and social impact as
      a risk factor for, psychosocial problems. Findings shed light on peer status as a
      mechanism underpinning female offenders' problem behaviors and an entry point for
      targeted interventions.

PMID- 25598650
TI  - Longitudinal Dynamic Analyses of Depression and Academic Achievement in the
      Hawaiian High Schools Health Survey using Contemporary Latent Variable Change
      Models.
AB  - The scientific literature consistently supports a negative relationship between
      adolescent depression and educational achievement, but we are certainly less sure
      on the causal determinants for this robust association. In this paper we present
      multivariate data from a longitudinal cohort-sequential study of high school
      students in Hawai'i (following McArdle, 2009; McArdle, Johnson, Hishinuma,
      Miyamoto, & Andrade, 2001). We first describe the full set of data on academic
      achievements and self-reported depression. We then carry out and present a
      progression of analyses in an effort to determine the accuracy, size, and
      direction of the dynamic relationships among depression and academic achievement,
      including gender and ethnic group differences. We apply three recently available
      forms of longitudinal data analysis: (1) Dealing with Incomplete Data -- We apply
      these methods to cohort-sequential data with relatively large blocks of data
      which are incomplete for a variety of reasons (Little & Rubin, 1987; McArdle &
      Hamagami, 1992). (2) Ordinal Measurement Models (Muthen & Muthen, 2006) -- We use
      a variety of statistical and psychometric measurement models, including ordinal
      measurement models to help clarify the strongest patterns of influence. (3)
      Dynamic Structural Equation Models (DSEMs; McArdle, 2009). We found the DSEM
      approach taken here was viable for a large amount of data, the assumption of an
      invariant metric over time was reasonable for ordinal estimates, and there were
      very few group differences in dynamic systems. We conclude that our dynamic
      evidence suggests that depression affects academic achievement, and not the other
      way around. We further discuss the methodological implications of the study.

PMID- 25598651
TI  - Adapting Cognitive-Behavioral Therapy for Depressed Adolescents Exposed to
      Interpersonal Trauma: A Case Study With Two Teens.
AB  - A substantial body of evidence indicates that interpersonal trauma increases risk
      for adolescent and adult depression. Findings from 4 clinical trials for
      adolescent depression show poorer response to standard cognitive-behavioral
      therapy (CBT) among depressed adolescents with a trauma history than youth
      without such a history. This paper reports on the development of a modified CBT
      (mCBT) protocol that has been adapted for treating depressed adolescents who have
      been exposed to traumatic interpersonal events (physical/sexual abuse or
      witnessing domestic violence). First, we provide an empirical rationale for
      targeting executive function deficits and trauma-related cognitions in the mCBT
      protocol. Second, we present promising results from 2 community clinic cases.

PMID- 25598652
TI  - 30-Month-Olds Use Verb Agreement Features in Online Sentence Processing.

PMID- 25598653
TI  - Patterns and Trends in Elder Homicide Across Race and Ethnicity, 1985-2009.
AB  - In this report, we assess total and race/ethnicity-disaggregated patterns and
      temporal trends in elderly homicide (age 55-74) compared with younger age groups
      for the 1985-to-2009 period. To do this, we use California arrest statistics that
      provide annual homicide figures by race and ethnicity (including a Hispanic
      identifier) and by age. Major aims of our analysis are to establish whether (a)
      elderly homicide rates are different/similar across race/ethnic comparisons; (b)
      the elderly share of homicide and age-homicide distributions more generally
      differ across race/ethnicity; and (c) elderly rates of homicide and the share of
      elderly homicide relative to younger age groups is similar or different now as
      compared with 20 to 30 years ago. Our analysis is important and timely because
      some commentators have suggested that elderly homicide levels have been rising
      over the past one to two decades and because there is a virtual absence of
      research of any sort on elderly homicide trends that involve comparisons by race
      and ethnicity. Key findings are that elderly shares of homicide offending
      relative to younger ages have not increased (or decreased), that elder homicides
      continue to account for a small fraction of all homicides, and that these
      patterns persist across race/ethnicity comparisons.

PMID- 25598654
TI  - Predictors of intent to pursue a college health science education among high
      achieving minority 10th graders.
AB  - Minority populations are underrepresented in fields of science, perhaps limiting
      scientific perspectives. Informed by recent studies using Social Cognitive Career
      Theory, this study examined whether three conceptual constructs: self-efficacy,
      perceived adult support, and perceptions of barriers, as well as several discrete
      and immutable variables, were associated with intent to pursue college science
      education in a sample (N = 134) of minority youth (70.1% female and 67.2% African
      American). A paper-and-pencil survey about pursuit of college science was
      administered to 10th graders with a B- or better grade point average from six
      high schools in an underserved community. Results indicated that the three
      conceptual constructs were bivariate correlates of intent to pursue college
      science education. Only perceived adult support and knowing whether a parent
      received college education were significant predictors in multivariate modeling.
      These results build on previous research and provide further insight into youth
      decision-making regarding pursuit of college science.

PMID- 25598655
TI  - Culture, Urbanism and Changing Human Biology.
AB  - Anthropologists have long known that human activity driven by culture changes the
      environment. This is apparent in the archaeological record and through the study
      of the modern environment. Perhaps the largest change since the paleolithic era
      is the organization of human populations in cities. New environments can reshape
      human biology through evolution as shown by the evolution of the hominid lineage.
      Evolution is not the only process capable of reshaping our biology. Some changes
      in our human biology are adaptive and evolutionary while others are pathological.
      What changes in human biology may be wrought by the modern urban environment? One
      significant new change in the environment is the introduction of pollutants
      largely through urbanization. Pollutants can affect human biology in myriad ways.
      Evidence shows that human growth, reproduction, and cognitive functioning can be
      altered by some pollutants, and altered in different ways depending on the
      pollutant. Thus, pollutants have significance for human biologists and
      anthropologists generally. Further, they illustrate the bio-cultural interaction
      characterizing human change. Humans adapt by changing the environment, a cultural
      process, and then change biologically to adjust to that new environment. This
      ongoing, interactive process is a fundamental characteristic of human change over
      the millennia.

PMID- 25598656
TI  - Plasma levels of 3-methoxy-4-hydroxyphenylglycol are associated with
      microstructural changes within the cerebellum in the early stage of first-episode
      schizophrenia: a longitudinal VBM study.
AB  - The aims of this study are to determine how the interval changes of the brain
      structures in the early stage of first-episode schizophrenia relate to the
      interval changes in the clinical data, including the clinical symptoms of
      schizophrenia and catecholaminergic measures (plasma homovanillic acid [HVA] and
      3-methoxy-4-hydroxyphenylglycol [MHPG]). Regional brain volumes and fractional
      anisotropy (FA)/mean diffusivity (MD) with diffusion tensor imaging (DTI) were
      measured at baseline and 6-month follow-up in a 3T magnetic resonance imaging
      (MRI) system in a cohort of 16 schizophrenic patients, who were in their first
      episode at the time of baseline MRI. At the time of baseline and follow-up MRI,
      all 16 patients underwent evaluations that included a psychopathological
      assessment (Positive and Negative Syndrome Scale [PANSS]) and peripheral
      catecholaminergic measures (plasma MHPG or HVA). For interval changes between
      baseline and follow-up MRI data (morphological change, MD, and FA), the
      correlation/regression analysis was performed as a series of single regression
      correlations in Statistical Parametric Mapping 5, with the interval changes in
      PANSS or plasma HVA and MHPG as the covariates of interest. Positive and inverse
      correlations contrasts were created, and in this preliminary analysis, a family
      wise error-corrected threshold of P<0.05 was considered significant. In the
      correlation/regression analysis, a positive correlation between the FA in the
      right cerebellar vermis and the MHPG was observed. No significant correlations
      between the brain volume or MD and any laboratory data (plasma HVA and MHPG) were
      found. During the 6-month follow-up in the early stage of first-episode
      schizophrenia, the MHPG changes were correlated with the microstructural FA
      changes in the cerebellum, which may reflect the functional connections of the
      noradrenergic system in the cerebellum. 

PMID- 25598657
TI  - Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer's disease
      modifying therapies.
AB  - Until now, a disease-modifying therapy (DMT) that has an ability to slow or
      arrest Alzheimer's disease (AD) progression has not been developed, and all
      clinical trials involving AD patients enrolled by clinical assessment alone also
      have not been successful. Given the growing consensus that the DMT is likely to
      require treatment initiation well before full-blown dementia emerges, the early
      detection of AD will provide opportunities to successfully identify new drugs
      that slow the course of AD pathology. Recent advances in early detection of AD
      and prediction of progression of the disease using various biomarkers, including
      cerebrospinal fluid (CSF) Abeta1-42, total tau and p-tau181 levels, and imagining
      biomarkers, are now being actively integrated into the designs of AD clinical
      trials. In terms of therapeutic mechanisms, monitoring these markers may be
      helpful for go/no-go decision making as well as surrogate markers for disease
      severity or progression. Furthermore, CSF biomarkers can be used as a tool to
      enrich patients for clinical trials with prospect of increasing statistical power
      and reducing costs in drug development. However, the standardization of technical
      aspects of analysis of these biomarkers is an essential prerequisite to the
      clinical uses. To accomplish this, global efforts are underway to standardize CSF
      biomarker measurements and a quality control program supported by the Alzheimer's
      Association. The current review summarizes therapeutic targets of developing
      drugs in AD pathophysiology, and provides the most recent advances in the. 

PMID- 25598658
TI  - Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization.
AB  - At central synapses, activity-dependent synaptic plasticity has a crucial role in
      information processing, storage, learning, and memory under both physiological
      and pathological conditions. One widely accepted model of learning mechanism and
      information processing in the brain is Hebbian Plasticity: long-term potentiation
      (LTP) and long-term depression (LTD). LTP and LTD are respectively activity
      dependent enhancement and reduction in the efficacy of the synapses, which are
      rapid and synapse-specific processes. A number of recent studies have a strong
      focal point on the critical importance of another distinct form of synaptic
      plasticity, non-Hebbian plasticity. Non-Hebbian plasticity dynamically adjusts
      synaptic strength to maintain stability. This process may be very slow and occur
      cell-widely. By putting them all together, this mini review defines an important
      conceptual difference between Hebbian and non-Hebbian plasticity. 

PMID- 25598659
TI  - Streptozotocin diabetes attenuates the effects of nondepolarizing neuromuscular
      relaxants on rat muscles.
AB  - The hypothesis of this study was that diabetes-induced desensitization of rat
      soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle
      relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We
      tested the different magnitude of resistance to vecuronium, cisatracurium, and
      rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the
      EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle
      preparations from rats after 4 and 16 weeks of STZ treatment. The concentration
      twitch tension curves were significantly shifted from those of the control group
      to the right in the diabetic groups. Concentration giving 50% of maximal
      inhibition (IC50) was larger in the diabetic groups for all the NDMRs. For
      rocuronium and cisatracurium in both SOL and EDL, IC50 was significantly larger
      in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL,
      the IC50 ratios were significantly largest in the diabetic 16 weeks group, second
      largest in the diabetic 4 weeks group, and smallest for the control group.
      Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and
      on the different kind of muscles observed while was independent on different kind
      of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16
      versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL,
      diabetes attenuated the actions of neuromuscular blockade more intensely than
      that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not
      relevant for the kind of NDMRs. 

PMID- 25598660
TI  - Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a
      Sodium Succinate Form of ZYM201.
AB  - DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside
      isolated from Sanguisorba officinalis, a medicinal plant prescribed for various
      diseases, such as duodenal ulcers and bleeding in East Asian counties. We
      demonstrated that this compound is able to normalize the altered lipid metabolism
      induced by hyperglycemia and a high fat diet. In this study, we determined
      whether hyperlipidemic conditions induced with chronically treated alcohol can
      also be restored by DWP208. Similar to our previous results, orally administered
      DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by
      alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i)
      up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL),
      very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride,
      and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as
      absolute body weight, superoxide dismutase (SOD) activity, and high-density
      lipoprotein (HDL) in serum and liver. According to our data, the ameliorative
      activity of DWP208 is due to its indirect anti-oxidative activity as a result of
      which lipid peroxide and hydroxyl radical levels were reduced and the activity of
      SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as
      a remedy against alcohol-induced hyperlipidemia. 

PMID- 25598662
TI  - The effects of ischemic postconditioning on myocardial function and nitric oxide
      metabolites following ischemia-reperfusion in hyperthyroid rats.
AB  - Ischemic postconditioning (IPost) could decrease ischemia-reperfusion (IR)
      injury. It has not yet reported whether IPost is useful when ischemic heart
      disease is accompanied with co-morbidities like hyperthyroidism. The aim of this
      study was to examine the effect of IPost on myocardial IR injury in hyperthyroid
      male rats. Hyperthyroidism was induced with administration of thyroxine in
      drinking water (12 mg/L) over a period of 21 days. After thoracotomy, the hearts
      of control and hyperthyroid rats were perfused in the Langendorff apparatus and
      subjected to 30 minutes global ischemia, followed by 120 minutes reperfusion;
      IPost, intermittent early reperfusion, was induced instantly following ischemia.
      In control rats, IPost significantly improved the left ventricular developed
      pressure (LVDP) and +/-dp/dt during reperfusion (p<0.05); however it had no
      effect in hyperthyroid rats. In addition, hyperthyroidism significantly increased
      basal NOx (nitrate+nitrite) content in serum (125.5+/-5.4 umol/L vs. 102.8+/-3.7
      umol/L; p< 0.05) and heart (34.9+/-4.1 umol/L vs. 19.9+/-1.94 umol/L; p<0.05). In
      hyperthyroid groups, heart NOx concentration significantly increased after IR and
      IPost, whereas in the control groups, heart NOx were significantly higher after
      IR and lower after IPost (p< 0.05). IPost reduced infarct size (p<0.05) only in
      control groups. In hyperthyroid group subjected to IPost, aminoguanidine, an
      inducible nitric oxide (NO) inhibitor, significantly reduced both the infarct
      size and heart NOx concentrations. In conclusion, unlike normal rats, IPost
      cycles following reperfusion does not provide cardioprotection against IR injury
      in hyperthyroid rats; an effect that may be due to NO overproduction because it
      is restored by iNOS inhibition. 

PMID- 25598661
TI  - FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-1alpha
      in the Presence of 27-hydroxycholesterol.
AB  - We investigated the question of whether cholesterol catabolite can influence
      expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic
      cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol)
      resulted in induction of gene transcription of TLR6 and elevated level of cell
      surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells
      resulted in transcription of the IL-1alpha gene and enhanced secretion of the
      corresponding gene product. However, cholesterol did not affect TLR6 expression,
      and addition of FSL-1 to cholesterol-treated cells did not induce expression of
      IL-1alpha. Using pharmacological inhibitors, we investigated molecular mechanisms
      underlying the expression of TLR6 and IL-1alpha. Treatment with Akt inhibitor IV
      or U0126 resulted in significantly attenuated expression of TLR6 and IL-1alpha
      induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment
      with LY294002, SB202190, or SP600125 resulted in significantly attenuated
      secretion of IL-1alpha. These results indicate that 27OHChol can induce
      inflammation by augmentation of TLR6-mediated production of IL-1alpha in
      monocytic cells via multiple signaling pathways. 

PMID- 25598663
TI  - Suppression of peripheral sympathetic activity underlies protease-activated
      receptor 2-mediated hypotension.
AB  - Protease-activated receptor (PAR)-2 is expressed in endothelial cells and
      vascular smooth muscle cells. It plays a crucial role in regulating blood
      pressure via the modulation of peripheral vascular tone. Although some reports
      have suggested involvement of a neurogenic mechanism in PAR-2-induced
      hypotension, the accurate mechanism remains to be elucidated. To examine this
      possibility, we investigated the effect of PAR-2 activation on smooth muscle
      contraction evoked by electrical field stimulation (EFS) in the superior
      mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic
      contractions evoked by EFS in endothelium-denuded superior mesenteric arterial
      strips but did not affect contraction elicited by the external application of
      noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on
      EFS-evoked contraction. Additionally, omega-conotoxin GVIA (CgTx), a selective N
      type Ca(2+) channel (ICa-N) blocker, significantly inhibited EFS-evoked
      contraction, and this blockade almost completely occluded the suppression of EFS
      evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS
      evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial
      strips and this suppression was nearly completely occluded by omega-CgTx. These
      results suggest that activation of PAR-2 may suppress peripheral sympathetic
      outflow by modulating activity of ICa-N which are located in peripheral
      sympathetic nerve terminals, which results in PAR-2-induced hypotension. 

PMID- 25598664
TI  - Scant Extracellular NAD Cleaving Activity of Human Neutrophils is Down-Regulated
      by fMLP via FPRL1.
AB  - Extracellular nicotinamide adenine dinucleotide (NAD) cleaving activity of a
      particular cell type determines the rate of the degradation of extracellular NAD
      with formation of metabolites in the vicinity of the plasma membrane, which has
      important physiological consequences. It is yet to be elucidated whether intact
      human neutrophils have any extracellular NAD cleaving activity. In this study,
      with a simple fluorometric assay utilizing 1,N(6)-ethenoadenine dinucleotide
      (etheno-NAD) as the substrate, we have shown that intact peripheral human
      neutrophils have scant extracellular etheno-NAD cleaving activity, which is much
      less than that of mouse bone marrow neutrophils, mouse peripheral neutrophils,
      human monocytes and lymphocytes. With high performance liquid chromatography
      (HPLC), we have identified that ADP-ribose (ADPR) is the major extracellular
      metabolite of NAD degradation by intact human neutrophils. The scant
      extracellular etheno-NAD cleaving activity is decreased further by N-formyl
      methionine-leucine-phenylalanine (fMLP), a chemoattractant for neutrophils. The
      fMLP-mediated decrease in the extracellular etheno-NAD cleaving activity is
      reversed by WRW4, a potent FPRL1 antagonist. These findings show that a much less
      extracellular etheno-NAD cleaving activity of intact human neutrophils compared
      to other immune cell types is down-regulated by fMLP via a low affinity fMLP
      receptor FPRL1. 

PMID- 25598666
TI  - Distinct Cellular Calcium Metabolism in Radiation-sensitive RKO Human Colorectal
      Cancer Cells.
AB  - Radiation therapy for variety of human solid tumors utilizes mechanism of cell
      death after DNA damage caused by radiation. In response to DNA damage, cytochrome
      c was released from mitochondria by activation of pro-apoptotic Bcl-2 family
      proteins, and then elicits massive Ca(2+) release from the ER that lead to cell
      death. It was also suggested that irradiation may cause the deregulation of
      Ca(2+) homeostasis and trigger programmed cell death and regulate death specific
      enzymes. Thus, in this study, we investigated how cellular Ca(2+) metabolism in
      RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma
      (gamma)-irradiation. In irradiated RKO cells, Ca(2+) influx via activation of NCX
      reverse mode was enhanced and a decline of [Ca(2+)]i via forward mode was
      accelerated. The amount of Ca(2+) released from the ER in RKO cells by the
      activation of IP3 receptor was also enhanced by irradiation. An increase in
      [Ca(2+)]i via SOCI was enhanced in irradiated RKO cells, while that in A549 cells
      was depressed. These results suggest that gamma-irradiation elicits enhancement
      of cellular Ca(2+) metabolism in radiation-sensitive RKO cells yielding
      programmed cell death. 

PMID- 25598667
TI  - Phasic and Tonic Inhibition are Maintained Respectively by CaMKII and PKA in the
      Rat Visual Cortex.
AB  - Phasic and tonic gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition
      critically regulate neuronal information processing. As these two inhibitory
      modalities have distinctive features in their receptor composition, subcellular
      localization of receptors, and the timing of receptor activation, it has been
      thought that they might exert distinct roles, if not completely separable, in the
      regulation of neuronal function. Inhibition should be maintained and regulated
      depending on changes in network activity, since maintenance of excitation
      inhibition balance is essential for proper functioning of the nervous system. In
      the present study, we investigated how phasic and tonic inhibition are maintained
      and regulated by different signaling cascades. Inhibitory postsynaptic currents
      were measured as either electrically evoked events or spontaneous events to
      investigate regulation of phasic inhibition in layer 2/3 pyramidal neurons of the
      rat visual cortex. Tonic inhibition was assessed as changes in holding currents
      by the application of the GABAA receptor blocker bicuculline. Basal tone of
      phasic inhibition was maintained by intracellular Ca(2+) and Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII). However, maintenance of tonic inhibition
      relied on protein kinase A activity. Depolarization of membrane potential (5 min
      of 0 mV holding) potentiated phasic inhibition via Ca(2+) and CaMKII but tonic
      inhibition was not affected. Thus, phasic and tonic inhibition seem to be
      independently maintained and regulated by different signaling cascades in the
      same cell. These results suggest that neuromodulatory signals might
      differentially regulate phasic and tonic inhibition in response to changes in
      brain states. 

PMID- 25598665
TI  - Transient receptor potential c4/5 like channel is involved in stretch-induced
      spontaneous uterine contraction of pregnant rat.
AB  - Spontaneous myometrial contraction (SMC) in pregnant uterus is greatly related
      with gestational age and growing in frequency and amplitude toward the end of
      gestation to initiate labor. But, an accurate mechanism has not been elucidated.
      In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant
      myometrium and among them, TRPC4 are predominant throughout gestation, suggesting
      a possible role in regulation of SMC. Therefore, we investigated whether the TRP
      channel may be involved SMC evoked by mechanical stretch in pregnant myometrial
      strips of rat using isometric tension measurement and patch-clamp technique. In
      the present results, hypoosmotic cell swelling activated a potent outward
      rectifying current in G protein-dependent manner in rat pregnant myocyte. The
      current was significantly potentiated by 1uM lanthanides (a potent TRPC4/5
      stimulator) and suppressed by 10uM 2-APB (TRPC4-7 inhibitor). In addition, in
      isometric tension experiment, SMC which was evoked by passive stretch was greatly
      potentiated by lanthanide (1uM) and suppressed by 2-APB (10uM), suggesting a
      possible involvement of TRPC4/5 channel in regulation of SMC in pregnant
      myometrium. These results provide a possible cellular mechanism for regulation of
      SMC during pregnancy and provide basic information for developing a new agent for
      treatment of premature labor. 

PMID- 25598668
TI  - TRPV1 in Salivary Gland Epithelial Cells Is Not Involved in Salivary Secretion
      via Transcellular Pathway.
AB  - Transient receptor potential vanilloid subtype 1 (TRPV1) was originally found in
      sensory neurons. Recently, it has been reported that TRPV1 is expressed in
      salivary gland epithelial cells (SGEC). However, the physiological role of TRPV1
      in salivary secretion remains to be elucidated. We found that TRPV1 is expressed
      in mouse and human submandibular glands (SMG) and HSG cells, originated from
      human submandibular gland ducts at both mRNA and protein levels. However,
      capsaicin (CAP), TRPV1 agonist, had little effect on intracellular free calcium
      concentration ([Ca(2+)]i) in these cells, although carbachol consistently
      increased [Ca(2+)]i. Exposure of cells to high temperature (>43C) or acidic bath
      solution (pH5.4) did not increase [Ca(2+)]i, either. We further examined the role
      of TRPV1 in salivary secretion using TRPV1 knock-out mice. There was no
      significant difference in the pilocarpine (PILO)-induced salivary flow rate
      between wild-type and TRPV1 knock-out mice. Saliva flow rate also showed
      insignificant change in the mice treated with PILO plus CAP compared with that in
      mice treated with PILO alone. Taken together, our results suggest that although
      TRPV1 is expressed in SGEC, it appears not to play any direct roles in saliva
      secretion via transcellular pathway. 

PMID- 25598670
TI  - Effect of papillary muscles and trabeculae on left ventricular measurement using
      cardiovascular magnetic resonance imaging in patients with hypertrophic
      cardiomyopathy.
AB  - OBJECTIVE: To evaluate the influence of papillary muscles and trabeculae on left
      ventricular (LV) cardiovascular magnetic resonance (CMR) analysis using three
      methods of cavity delineation (classic or modified inclusion methods, and the
      exclusion method) in patients with hypertrophic cardiomyopathy (HCM). MATERIALS
      AND METHODS: This retrospective study included 20 consecutive HCM patients who
      underwent 1.5-T CMR imaging with short-axis cine stacks of the entire LV. LV
      measurements were performed using three different methods of manual cavity
      delineation of the endocardial and epicardial contours: method A, presumed
      endocardial boundary as seen on short-axis cine images; method B, including
      solely the cavity and closely adjacent trabeculae; or method C, excluding
      papillary muscles and trabeculae. Ascending aorta forward flow was measured as
      reference for LV-stroke volume (SV). Interobserver reproducibility was assessed
      using intraclass correlation coefficients. RESULTS: Method A showed larger end
      diastole and end-systole volumes (largest percentage differences of 25% and 68%,
      respectively, p < 0.05), compared with method C. The ejection fraction was 55.7
      +/- 6.9% for method A, 68.6 +/- 8.4% for B, and 71.7 +/- 7.0% for C (p < 0.001).
      Mean mass was also significantly different: 164.6 +/- 47.4 g for A, 176.5 +/-
      50.5 g for B, and 199.6 +/- 53.2 g for C (p < 0.001). LV-SV error was largest
      with method B (p < 0.001). No difference in interobserver agreement was observed
      (p > 0.05). CONCLUSION: In HCM patients, LV measurements are strikingly different
      dependent on whether papillary muscles and trabeculae are included or excluded.
      Therefore, a consistent method of LV cavity delineation may be crucial during
      longitudinal follow-up to avoid misinterpretation and erroneous clinical decision
      making.

PMID- 25598671
TI  - Evaluation of a chest circumference-adapted protocol for low-dose 128-slice
      coronary CT angiography with prospective electrocardiogram triggering.
AB  - OBJECTIVE: To assess the effect of chest circumference-adapted scanning protocol
      on radiation exposure and image quality in patients undergoing prospective
      electrocardiogram (ECG)-triggered coronary CT angiography (CCTA). MATERIALS AND
      METHODS: One hundred-eighty-five consecutive patients, who had undergone
      prospective ECG triggering CCTA with a 128-slice CT, were included in the present
      study. Nipple-level chest circumference, body weight and height were measured
      before CT examinations. Patients were divided into four groups based on kV/ref .
      mAs = 100/200, 100/250, 120/200, and 120/250, when patient's chest circumference
      was <= 85.0 (n = 56), 85.0-90.0 (n = 53), 90.0-95.0 (n = 44), and > 95.0 (n =
      32), respectively. Image quality per-segment was independently assessed by two
      experienced observers. Image noise and attenuation were also measured. Signal-to
      noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The
      effective radiation dose was calculated using CT dose volume index and the dose
      length product. RESULTS: A significant correlation was observed between patients'
      chest circumference and body mass index (r = 0.762, p < 0.001). Chest
      circumference ranged from 74 to 105 cm, and the mean effective radiation dose was
      1.9-3.8 mSv. Diagnostic image quality was obtained in 98.5% (2440/2478) of all
      evaluated coronary segments without any significant differences among the four
      groups (p = 0.650). No significant difference in image noise was observed among
      the four groups (p = 0.439), thus supporting the validity of the chest
      circumference-adapted scanning protocol. However, vessel attenuation, SNR and CNR
      were significantly higher in the 100 kV groups than in the 120 kV groups (p <
      0.05). CONCLUSION: A measure of chest circumference can be used to adapt tube
      voltage and current for individualized radiation dose control, with resultant
      similar image noise and sustained diagnostic image quality.

PMID- 25598672
TI  - Current status of optical imaging for evaluating lymph nodes and lymphatic
      system.
AB  - Optical imaging techniques use visual and near infrared rays. Despite their
      considerably poor penetration depth, they are widely used due to their safe and
      intuitive properties and potential for intraoperative usage. Optical imaging
      techniques have been actively investigated for clinical imaging of lymph nodes
      and lymphatic system. This article summarizes a variety of optical tracers and
      techniques used for lymph node and lymphatic imaging, and reviews their clinical
      applications. Emerging new optical imaging techniques and their potential are
      also described. 

PMID- 25598673
TI  - Integrated whole body MR/PET: where are we?
AB  - Whole body integrated magnetic resonance imaging (MR)/positron emission
      tomography (PET) imaging systems have recently become available for clinical use
      and are currently being used to explore whether the combined anatomic and
      functional capabilities of MR imaging and the metabolic information of PET
      provide new insight into disease phenotypes and biology, and provide a better
      assessment of oncologic diseases at a lower radiation dose than a CT. This review
      provides an overview of the technical background of combined MR/PET systems, a
      discussion of the potential advantages and technical challenges of hybrid MR/PET
      instrumentation, as well as collection of possible solutions. Various early
      clinical applications of integrated MR/PET are also addressed. Finally, the
      workflow issues of integrated MR/PET, including maximizing diagnostic information
      while minimizing acquisition time are discussed. 

PMID- 25598675
TI  - Attenuation-based automatic kilovoltage selection and sinogram-affirmed iterative
      reconstruction: effects on radiation exposure and image quality of portal-phase
      liver CT.
AB  - OBJECTIVE: To compare the radiation dose and image quality between standard-dose
      CT and a low-dose CT obtained with the combined use of an attenuation-based
      automatic kilovoltage (kV) selection tool (CARE kV) and sinogram-affirmed
      iterative reconstruction (SAFIRE) for contrast-enhanced CT examination of the
      liver. MATERIALS AND METHODS: We retrospectively reviewed 67 patients with
      chronic liver disease in whom both, standard-dose CT with 64-slice multidetector
      row CT (MDCT) (protocol A), and low-dose CT with 128-slice MDCT using CARE kV and
      SAFIRE (protocol B) were performed. Images from protocol B during the portal
      phase were reconstructed using either filtered back projection or SAFIRE with 5
      different iterative reconstruction (IR) strengths. We performed qualitative and
      quantitative analyses to select the appropriate IR strength. Reconstructed images
      were then qualitatively and quantitatively compared with protocol A images.
      RESULTS: Qualitative and quantitative analysis of protocol B demonstrated that
      SAFIRE level 2 (S2) was most appropriate in our study. Qualitative and
      quantitative analysis comparing S2 images from protocol B with images from
      protocol A, showed overall good diagnostic confidence of S2 images despite a
      significant radiation dose reduction (47% dose reduction, p < 0.001). CONCLUSION:
      Combined use of CARE kV and SAFIRE allowed significant reduction in radiation
      exposure while maintaining image quality in contrast-enhanced liver CT.

PMID- 25598674
TI  - Cancer stem cells in primary liver cancers: pathological concepts and imaging
      findings.
AB  - There is accumulating evidence that cancer stem cells (CSCs) play an integral
      role in the initiation of hepatocarcinogenesis and the maintaining of tumor
      growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential
      to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers
      originating from CSCs constitute a heterogeneous histopathologic spectrum,
      including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma,
      and intrahepatic cholangiocarcinoma with various radiologic manifestations. In
      this article, we reviewed the recent concepts of CSCs in the development of
      primary liver cancers, focusing on their pathological and radiological findings.
      Awareness of the pathological concepts and imaging findings of primary liver
      cancers with features of CSCs is critical for accurate diagnosis, prediction of
      outcome, and appropriate treatment options for patients. 

PMID- 25598676
TI  - The role of three-dimensional multidetector CT gastrography in the preoperative
      imaging of stomach cancer: emphasis on detection and localization of the tumor.
AB  - Multidetector CT (MDCT) gastrography has been regarded as a promising technique
      for the preoperative imaging of gastric cancer. It has the ability to produce
      various three-dimensional (3D) images. Because 3D reconstruction images are more
      effective and intuitive for recognizing abnormal changes in the gastric folds and
      subtle mucosal nodularity than two-dimensional images, 3D MDCT gastrography can
      enhance the detection rate of early gastric cancer, which, in turn, contributes
      to the improvement of the accuracy of preoperative tumor (T) staging. In
      addition, shaded surface display and tissue transition projection images provide
      a global view of the stomach, with the exact location of gastric cancer, which
      may replace the need for barium studies. In this article, we discuss technical
      factors in producing high-quality MDCT gastrographic images and present cases
      demonstrating the usefulness of MDCT gastrography for the detection and T staging
      of gastric cancer while emphasizing the significance of preoperative localization
      of gastric cancer in terms of surgical margin. 

PMID- 25598677
TI  - Magnetic resonance imaging-guided prostate biopsy: present and future.
AB  - Systemic transrectal ultrasound-guided biopsy (TRUSBx) is the standard procedure
      for diagnosing prostate cancer (PCa), but reveals a limited accuracy for the
      detection of cancer. Currently, multiparametric MR imaging (mp-MRI) is
      increasingly regarded as a promising method to detect PCa with an excellent
      positive predictive value. The use of mp-MRI during a MRI-guided biopsy (MRGB)
      procedure improves the quality of a targeted biopsy. The aim of this article is
      to provide an overview about the MRGB technique for PCa detection, to review the
      accuracy and clinical indications of MRGB and discuss its current issues and
      further directions. A MRGB seems accurate and efficient for the detection of
      clinically significant PCa in men with previous negative TRUSBx. Moreover, it may
      decrease the detection of clinically insignificant cancers with fewer biopsy
      cores. 

PMID- 25598679
TI  - Role of C-arm cone-beam CT in chemoembolization for hepatocellular carcinoma.
AB  - With the advent of C-arm cone-beam computed tomography (CBCT), minimally-invasive
      procedures in the angiography suite made a new leap beyond the limitations of 2
      dimensional (D) angiography alone. C-arm CBCT can help interventional
      radiologists in several ways with the treatment of hepatocellular carcinoma
      (HCC); visualization of small tumors and tumor-feeding arteries, identification
      of occult lesion and 3D configuration of tortuous hepatic arteries, assurance of
      completeness of chemoembolization, suggestion of presence of extrahepatic
      collateral arteries supplying HCCs, and prevention of nontarget embolization.
      With more improvements in the technology, C-arm CBCT may be essential in all
      kinds of interventional procedures in the near future. 

PMID- 25598678
TI  - Imaging findings of common benign renal tumors in the era of small renal masses:
      differential diagnosis from small renal cell carcinoma: current status and future
      perspectives.
AB  - The prevalence of small renal masses (SRM) has risen, paralleling the increased
      usage of cross-sectional imaging. A large proportion of these SRMs are not
      malignant, and do not require invasive treatment such as nephrectomy. Therefore,
      differentiation between early renal cell carcinoma (RCC) and benign SRM is
      critical to achieve proper management. This article reviews the radiological
      features of benign SRMs, with focus on two of the most common benign entities,
      angiomyolipoma and oncocytoma, in terms of their common imaging findings and
      differential features from RCC. Furthermore, the role of percutaneous biopsy is
      discussed as imaging is yet imperfect, therefore necessitating biopsy in certain
      circumstances to confirm the benignity of SRMs.

PMID- 25598680
TI  - Transarterial chemoembolization using gelatin sponges or microspheres plus
      lipiodol-doxorubicin versus doxorubicin-loaded beads for the treatment of
      hepatocellular carcinoma.
AB  - OBJECTIVE: To retrospectively compare treatment of hepatocellular carcinoma (HCC)
      with transarterial chemoembolization (TACE) using gelatin sponges or microspheres
      plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB).
      MATERIALS AND METHODS: A total of 158 patients with HCC received TACE from
      November 2010 to November 2011 were enrolled in this study, including 64 (40.5%)
      received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%)
      received TACE with lipiodol-doxorubicin and microspheres (group B), and 53
      (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and
      adverse events (AEs) were evaluated. RESULTS: No significant difference was found
      at baseline among the three groups. The doxorubicin dosage in group C was
      significantly (p < 0.001) higher compared to the dose used in groups A or B
      (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in
      group C achieved complete response compared to those in groups A or B (32.1% vs.
      6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive
      disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs
      were more common in groups A and B compared to group C, with rates of 54.7%,
      34.1%, and 5.7%, respectively. CONCLUSION: In patients with HCC, TACE with DEB
      offers better safety and efficacy profiles compared to either TACE with gelatin
      sponges or TACE with microspheres.

PMID- 25598681
TI  - Evaluation of arterial impairment after experimental gelatin sponge embolization
      in a rabbit renal model.
AB  - OBJECTIVE: Arterial stenosis is a major obstacle for subsequent interventional
      procedures. We hypothesized that the stenosis is caused by gelatin sponge
      embolization and performed an experimental study in a rabbit renal model.
      MATERIALS AND METHODS: A total of 24 rabbits were embolized with porcine gelatin
      sponge particles injected into the renal arteries. Four rabbits were sacrificed
      on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization.
      Microscopic evaluations were performed on hematoxylin-eosin and smooth muscle
      actin immunohistochemical stained sections. RESULTS: Gelatin sponge particles
      were mainly observed in the segmental and interlobar arteries. Transmural
      inflammation of the embolized arterial wall and mild thickening of the media were
      observed 1 week after embolization. Resorption of the gelatin sponge and
      organization of thrombus accompanied by foreign body reactions, were observed
      from 2 to 4 weeks after embolization. Microscopic images of the 3 weeks group
      showed vessel lumens filled mostly with organized thrombi, resulting in severe
      stenosis. Additionally, vessels showed a thickened intima that contained
      migrating smooth muscle cells and accompanying interruption of the internal
      elastic lamina. The migrating smooth muscle cells were distributed around the
      recanalized arterial lumen. CONCLUSION: Gelatin sponge embolization may induce
      arterial stenosis by causing organized thrombus and intimal hyperplasia, which
      consists of migrating smooth muscle cells and intimal collagen deposits.

PMID- 25598682
TI  - Segmental quantitative MR imaging analysis of diurnal variation of water content
      in the lumbar intervertebral discs.
AB  - OBJECTIVE: To investigate the changes in water content in the lumbar
      intervertebral discs by quantitative T2 MR imaging in the morning after bed rest
      and evening after a diurnal load. MATERIALS AND METHODS: Twenty healthy
      volunteers were separately examined in the morning after bed rest and in the
      evening after finishing daily work. T2-mapping images were obtained and analyzed.
      An equally-sized rectangular region of interest (ROI) was manually placed in
      both, the anterior and the posterior annulus fibrosus (AF), in the outermost 20%
      of the disc. Three ROIs were placed in the space defined as the nucleus pulposus
      (NP). Repeated-measures analysis of variance and paired 2-tailed t tests were
      used for statistical analysis, with p < 0.05 as significantly different. RESULTS:
      T2 values significantly decreased from morning to evening, in the NP (anterior NP
      = -13.9 ms; central NP = -17.0 ms; posterior NP = -13.3 ms; all p < 0.001).
      Meanwhile T2 values significantly increased in the anterior AF (+2.9 ms; p =
      0.025) and the posterior AF (+5.9 ms; p < 0.001). T2 values in the posterior AF
      showed the largest degree of variation among the 5 ROIs, but there was no
      statistical significance (p = 0.414). Discs with initially low T2 values in the
      center NP showed a smaller degree of variation in the anterior NP and in the
      central NP, than in discs with initially high T2 values in the center NP (10.0%
      vs. 16.1%, p = 0.037; 6.4% vs. 16.1%, p = 0.006, respectively). CONCLUSION:
      Segmental quantitative T2 MRI provides valuable insights into physiological
      aspects of normal discs.

PMID- 25598683
TI  - Pelvic solitary plasmacytoma: computed tomography and magnetic resonance imaging
      findings with histopathologic correlation.
AB  - OBJECTIVE: To describe the imaging features of pelvic solitary plasmacytoma and
      to correlate them with the pathologic grade. MATERIALS AND METHODS: A
      retrospective study was performed on the imaging features of 10 patients with a
      histological diagnosis of pelvic solitary plasmacytoma. The imaging studies were
      assessed for bone expansion, cortical destruction, signal intensity/density of
      soft tissue mass and enhancement manifestations, which were then correlated to
      the pathologic grade. RESULTS: The imaging features of pelvic solitary
      plasmacytoma revealed 3 different types: multilocular type (n = 5), unilocular
      type (n = 2) and complete osteolytic destruction type (n = 3) on computed
      tomography and MRI. Pathologically, the tumors were classified into low,
      intermediate and high grades. Features such as multilocular change, perilesional
      osteosclerosis, slight expansion, local bone cortex disruptions and masses inside
      bone destruction, often suggest a low-grade solitary plasmacytoma; complete
      osteolytic destruction, huge soft tissue mass, and osseous defects imply a higher
      pathologic grade. CONCLUSION: Pelvic solitary plasmacytoma has various imaging
      manifestations, while a slight expansile osteolytic feature with multilocular
      change or homogeneous enhancement highly suggests its diagnosis. The distinctive
      imaging features of pelvic solitary plasmacytoma are well correlated to the
      pathologic grade.

PMID- 25598684
TI  - Rapid increase in marrow fat content and decrease in marrow perfusion in lumbar
      vertebra following bilateral oophorectomy: an MR imaging-based prospective
      longitudinal study.
AB  - OBJECTIVE: Bilateral oophorectomy leads to reduced bone mineral density (BMD),
      and reduced BMD is associated with increased marrow fat and reduced marrow
      perfusion. Purpose of this study was to investigate how soon these changes occur
      following surgical oophorectomy. MATERIALS AND METHODS: Six patients who
      underwent hysterectomy and bilateral salpingo-oophorectomy were studied. At
      baseline, mean patient age was 49.5 years (range: 45-54 years). Third lumbar
      vertebral body BMD measurement using quantitative CT, marrow fat fraction (FF)
      using MR spectroscopy and marrow perfusion using dynamic contrast enhanced MRI
      were conducted immediately prior to surgery and at 3, 9, and 21 months after
      surgery. RESULTS: Reduced BMD, increased marrow FF, and reduced marrow perfusion
      occurred synchronously post-oophorectomy. There was a sharp decrease of 12.5 +/-
      7.2% in BMD (n = 6), a sharp increase of 92.2 +/- 46.3% (n = 6) in FF, a sharp
      decrease of 23.6 +/- 3.9% in maximum contrast enhancement (n = 5), and of 45.4 +/
      7.7% for enhancement slope (n = 5) during the initial 3 months post surgery. BMD
      and marrow perfusion continued to decrease, and marrow FF continued to increase
      at a slower rate during the following 18 months. Friedman test showed a
      significant trend for these changes (p < 0.05). CONCLUSION: Bilateral
      oophorectomy leads to a rapid decrease in lumbar BMD, an increase in marrow fat
      content, and a decrease in marrow blood perfusion.

PMID- 25598685
TI  - MR imaging appearances of soft tissue flaps following reconstructive surgery of
      the lower extremity.
AB  - MR imaging appearances of different types of reconstructive muscle flaps
      following reconstructive surgery of the lower extremity with associated post
      surgical changes due to altered anatomy, radiation, and potential complications,
      can be challenging. A multidisciplinary therapeutic approach to tumors allows for
      limb salvage therapy in a majority of the patients. Decision-making for specific
      types of soft tissue reconstruction is based on the body region affected, as well
      as the size and complexity of the defect. Hematomas and infections are early
      complications that can jeopardize flap viability. The local recurrence of a tumor
      within six months after a complete resection with confirmed tumor-free margins
      and adjuvant radiation therapy is rare. Identification of a new lesion similar to
      the initial tumor favors a finding of tumor recurrence. 

PMID- 25598686
TI  - Intra-articular fibroma of tendon sheath in a knee joint associated with
      iliotibial band friction syndrome.
AB  - Iliotibial band (ITB) friction syndrome is a common overuse injury typically seen
      in the active athlete population. A nodular lesion on the inner side of the ITB
      as an etiology or an accompanying lesion from friction syndrome has been rarely
      reported. A 45-year-old male presented with recurrent pain and a movable nodule
      at the lateral joint area, diagnosed as ITB friction syndrome. The nodule was
      confirmed as a rare intra-articular fibroma of the tendon sheath (FTS) on the
      basis of histopathologic findings. We describe the MRI findings, arthroscopic and
      pathologic features, in this case of intra-articular FTS presenting with ITB
      friction syndrome. 

PMID- 25598687
TI  - Solitary osseous metastasis of rectal carcinoma masquerading as osteogenic
      sarcoma on post-chemotherapy imaging: a case report.
AB  - Solitary metastases from colorectal carcinoma in the absence of hepatic or
      pulmonary metastases are rare. These can have a diverse imaging appearance,
      particularly after chemotherapy. It is important identify patients with solitary
      skeletal metastases, as they have a better prognosis than those with multiple
      skeletal or visceral metastases. We describe an unusual case of a solitary
      metastasis to the femur in a case of colon carcinoma that went undiagnosed and
      later presented with imaging features of osteogenic sarcoma. 

PMID- 25598688
TI  - Simultaneous endovascular treatment of ruptured cerebral aneurysms and vasospasm.
AB  - OBJECTIVE: The management of patients with ruptured cerebral aneurysms and severe
      vasospasm is subject to considerable controversy. We intended to describe herein
      an endovascular technique for the simultaneous treatment of aneurysms and
      vasospasm. MATERIALS AND METHODS: A series of 11 patients undergoing simultaneous
      endovascular treatment of ruptured aneurysms and vasospasm were reviewed. After
      placement of a guiding catheter within the proximal internal carotid artery for
      coil embolization, an infusion line of nimodipine was wired to one hub, and of a
      microcatheter was advanced through another hub (to select and deliver detachable
      coils). Nimodipine was then infused continuously during the coil embolization.
      RESULTS: This technique was applied to 11 ruptured aneurysms accompanied by
      vasospasm (anterior communicating artery, 6 patients; internal carotid artery, 2
      patients; posterior communicating and middle cerebral arteries, 1 patient each).
      Aneurysmal occlusion by coils and nimodipine-induced angioplasty were
      simultaneously achieved, resulting in excellent outcomes for all patients, and
      there were no procedure-related complications. Eight patients required repeated
      nimodipine infusions. CONCLUSION: Our small series of patients suggests that the
      simultaneous endovascular management of ruptured cerebral aneurysms and vasospasm
      is a viable approach in patients presenting with subarachnoid hemorrhage and
      severe vasospasm.

PMID- 25598689
TI  - Primary lymphedema of the lower limb: the clinical utility of single photon
      emission computed tomography/CT.
AB  - OBJECTIVE: The aim of this prospective study was to determine whether the
      additional use of the single photon emission computed tomography/CT (SPECT/CT)
      technique improves the diagnostic value of planar lymphoscintigraphy in patients
      presenting with primary lymph edema of the lower limb. MATERIALS AND METHODS: For
      a defined period of three years (April 2011-April 2014) a total of 34 consecutive
      patients (28 females; age range, 27-83 years) presenting with swelling of the
      leg(s) suspicious of (uni- or bilateral, proximal or distal) primary lymphedema
      were prospectively examined by planar lymphoscintigraphy (lower limbs, n = 67)
      and the tomographic SPECT/CT technique (anatomical sides, n = 65). RESULTS: In
      comparison to pathological planar scintigraphic findings, the addition of
      SPECT/CT provided relevant additional information regarding the presence of
      dermal backflow (86%), the anatomical extent of lymphatic disorders (64%), the
      presence or absence of lymph nodes (46%), and the visualization of lymph vessels
      (4%). CONCLUSION: As an adjunct to planar lymphoscintigraphy, SPECT/CT specifies
      the anatomical correlation of lymphatic disorders and thus improves assessment of
      the extent of pathology due to the particular advantages of tomographic
      separation of overlapping sources. The interpretation of scintigraphic data
      benefits not only in baseline diagnosis, but also in physiotherapeutical and
      microsurgical treatments of primary lymphedema.

PMID- 25598690
TI  - Charcoal-induced granuloma that mimicked a nodal metastasis on ultrasonography
      and FDG-PET/CT after neck dissection.
AB  - Charcoal can be used for preoperative localization of metastatic lymph nodes in
      the neck. Charcoal remains stable without causing foreign body reactions during
      as hort period. However, foreign body reactions may develop if charcoal is left
      in situ for more than 6 months. We reported a case of charcoal granuloma
      mimicking local recurrence on fluorodeoxyglucose-positron emission
      tomography/computed tomography and ultrasonography in a 47-year-old woman who had
      cervical lymph node dissection due to metastatic invasive ductal carcinoma of the
      breast. 

PMID- 25598691
TI  - Assessment of bone age in prepubertal healthy Korean children: comparison among
      the Korean standard bone age chart, Greulich-Pyle method, and Tanner-Whitehouse
      method.
AB  - OBJECTIVE: To compare the reliability of the Greulich-Pyle (GP) method, Tanner
      Whitehouse 3 (TW3) method and Korean standard bone age chart (KS) in the
      evaluation of bone age of prepubertal healthy Korean children. MATERIALS AND
      METHODS: Left hand-wrist radiographs of 212 prepubertal healthy Korean children
      aged 7 to 12 years, obtained for the evaluation of the traumatic injury in
      emergency department, were analyzed by two observers. Bone age was estimated
      using the GP method, TW3 method and KS, and was calculated in months. The
      correlation between bone age measured by each method and chronological age of
      each child was analyzed using Pearson correlation coefficient, scatterplot. The
      three methods were compared using one-way analysis of variance. RESULTS:
      Significant correlations were found between chronological age and bone age
      estimated by all three methods in whole group and in each gender (R(2) ranged
      from 0.87 to 0.9, p < 0.01). Although bone age estimated by KS was slightly
      closer to chronological age than those estimated by the GP and TW3 methods, the
      difference between three methods was not statistically significant (p > 0.01).
      CONCLUSION: The KS, GP, and TW3 methods show good reliability in the evaluation
      of bone age of prepubertal healthy Korean children without significant difference
      between them. Any are useful for evaluation of bone age in prepubertal healthy
      Korean children.

PMID- 25598694
TI  - Increasing the strength of nanocrystalline steels by annealing: Is segregation
      necessary?
AB  - Hardening phenomena in nanocrystalline metals after annealing have been widely
      reported, and the subject of much recent debate. Solute segregation to grain
      boundaries and dislocation source hardening have been proposed to cause the
      strengthening. To shed light on the dominant mechanisms, we present results from
      mechanical experiments and atom probe tomography on samples with similar grain
      size but different amounts of solute segregation and different boundary
      chemistries.

PMID- 25598693
TI  - The pleural sandwich sign in two cases of primary pleural lymphoma.
AB  - The sandwich sign is used to describe mesenteric lymphoma in which mesenteric
      vessels and fat are enveloped by enlarged mesenteric lymph nodes. We present two
      cases of primary pleural lymphoma demonstrating the "pleural sandwich sign".
      Contrast-enhanced computed tomography showed conglomerated parietal pleural and
      extrapleural masses encasing the intercostal arteries. Histopathological
      examinations confirmed low grade marginal zone B-cell lymphoma in an 80-year-old
      man and diffuse large B-cell lymphoma in a 68-year-old man. The pleural sandwich
      sign may suggest the diagnosis of primary pleural lymphoma. 

PMID- 25598692
TI  - CT-guided core needle biopsy of pleural lesions: evaluating diagnostic yield and
      associated complications.
AB  - OBJECTIVE: The purpose of this study was to retrospectively evaluate the
      diagnostic accuracy and complications of CT-guided core needle biopsy (CT-guided
      CNB) of pleural lesion and the possible effects of influencing factors. MATERIALS
      AND METHODS: From September 2007 to June 2013, 88 consecutive patients (60 men
      and 28 women; mean [+/- standard deviation] age, 51.1 +/- 14.4 years; range, 19
      78 years) underwent CT-guided CNB, which was performed by two experienced chest
      radiologists in our medical center. Out of 88 cases, 56 (63%) were diagnosed as
      malignant, 28 (31%) as benign and 4 (5%) as indeterminate for CNB of pleural
      lesions. The final diagnosis was confirmed by either histopathological diagnosis
      or clinical follow-up. The diagnostic accuracy, sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV), and
      complication rates were statistically evaluated. Influencing factors (patient
      age, sex, lesion size, pleural-puncture angle, patient position, pleural
      effusion, and number of pleural punctures) were assessed for their effect on
      accuracy of CT-guided CNB using univariate and subsequent multivariate analysis.
      RESULTS: Diagnostic accuracy, sensitivity, specificity, PPV, and NPV were 89.2%,
      86.1%, 100%, 100%, and 67.8%, respectively. The influencing factors had no
      significant effect in altering diagnostic accuracy. As far as complications were
      concerned, occurrence of pneumothorax was observed in 14 (16%) out of 88
      patients. Multivariate analysis revealed lesion size/pleural thickening as a
      significant risk factor (odds ratio [OR]: 8.744, p = 0.005) for occurrence of
      pneumothorax. Moreover, presence of pleural effusion was noted as a significant
      protective factor (OR: 0.171, p = 0.037) for pneumothorax. CONCLUSION: CT-guided
      CNB of pleural lesion is a safe procedure with high diagnostic yield and low risk
      of significant complications.

PMID- 25598695
TI  - Control of sleep-to-wake transitions via fast aminoacid and slow neuropeptide
      transmission.
AB  - The Locus Coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem
      and spinal cord circuits and it expresses receptors for neuromodulators that
      operate in a time scale of several seconds. Evidences from anatomical,
      electrophysiological and optogenetic experiments have shown that LC neurons
      receive input from a group of neurons called Hypocretins (HCRTs) that release a
      neuropeptide called hypocretin. It is less known how these two groups of neurons
      can be coregulated using GABAergic neurons. Since the time scales of GABA A
      inhibition is several orders of magnitude faster than the hypocretin neuropeptide
      effect, we investigate the limits of circuit activity regulation using a
      realistic model of neurons. Our investigation shows that GABA A inhibition is
      insufficient to control the activity levels of the LCs. Despite slower forms of
      GABA A can in principle work, there is not much plausibility due to the low
      probability of the presence of slow GABA A and lack of robust stability at the
      maximum firing frequencies. The best possible control mechanism predicted by our
      modeling analysis is the presence of inhibitory neuropeptides that exert effects
      in a similar time scale as the hypocretin/orexin. Although the nature of these
      inhibitory neuropeptides has not been identified yet, it provides the most
      efficient mechanism in the modeling analysis. Finally, we present a reduced mean
      field model that perfectly captures the dynamics and the phenomena generated by
      this circuit. This investigation shows that brain communication involving
      multiple time scales can be better controlled by employing orthogonal mechanisms
      of neural transmission to decrease interference between cognitive processes and
      hypothalamic functions.

PMID- 25598696
TI  - Modeling physicochemical interactions affecting in vitro cellular dosimetry of
      engineered nanomaterials: application to nanosilver.
AB  - Engineered nanomaterials (ENMs) possess unique characteristics affecting their
      interactions in biological media and biological tissues. Systematic investigation
      of the effects of particle properties on biological toxicity requires a
      comprehensive modeling framework which can be used to predict ENM particokinetics
      in a variety of media. The Agglomeration-diffusion-sedimentation-reaction model
      (ADSRM) described here is stochastic, using a direct simulation Monte Carlo
      method to study the evolution of nanoparticles in biological media, as they
      interact with each other and with the media over time. Nanoparticle diffusion,
      gravitational settling, agglomeration, and dissolution are treated in a
      mechanistic manner with focus on silver ENMs (AgNPs). The ADSRM model utilizes
      particle properties such as size, density, zeta potential, and coating material,
      along with medium properties like density, viscosity, ionic strength, and pH, to
      model evolving patterns in a population of ENMs along with their interaction with
      associated ions and molecules. The model predictions for agglomeration and
      dissolution are compared with in vitro measurements for various types of ENMs,
      coating materials, and incubation media, and are found to be overall consistent
      with measurements. The model has been implemented for an in vitro case in cell
      culture systems to inform in vitro dosimetry for toxicology studies, and can be
      directly extended to other biological systems, including in vivo tissue
      subsystems by suitably modifying system geometry.

PMID- 25598697
TI  - MicroRNAs: Important Epigenetic Regulators in Osteoarthritis.
AB  - Multiple mechanisms are implicated in the development of primary osteoarthritis
      (OA), in which genetic and epigenetic factors appear to interact with
      environmental factors and age to initiate the disease and stimulate its
      progression. Changes in expression of microRNAs (miRs) contribute to development
      of osteoarthritis. Numerous miRs are involved in cartilage development,
      homeostasis and degradation through targeting genes expressed in this tissue. An
      important regulator of gene expression in human cartilage is miR-140, which
      directly targets a gene coding aggrecanase ADAMTS-5, that cleaves aggrecan in
      cartilage. This miR is considered a biological marker for cartilage and its level
      significantly decreases in OA cartilage. On the other hand, increased expression
      of miR-146a in early OA inhibits two other cartilage-degrading enzymes: MMP13 and
      ADAMTS4, and may provide a useful tool in developing treatments for OA. The
      COL2A1 gene, encoding collagen type II, which is the most abundant structural
      protein of the cartilage, is silenced by miR-34a and activated by miR-675. Every
      year, new targets of cartilage miRs are validated experimentally and this opens
      new possibilities for new therapies that control joint destruction and stimulate
      cartilage repair. At the same time development of next-generation sequencing
      technologies allows to identify new miRs involved in cartilage biology. 

PMID- 25598699
TI  - Acceptable pregnancy rate of unstimulated intrauterine insemination: a
      retrospective analysis of 17,830 cycles.
AB  - PURPOSE: To evaluate the pregnancy rate (PR) of unstimulated intrauterine
      insemination (IUI). METHODS: This was a retrospective study in a private
      fertility clinic. Between 2004 and 2013, a total of 4,045 women underwent 17,830
      cycles of unstimulated IUI. The etiologies of subfertility in the couples were
      unexplained (51 %), male factor (36 %), coital problems (9.5 %), and cervical
      factor (3.5 %). RESULTS: The PRs/cycle, between the 1st and 9th trials, in women
      <35, 35-37, 38-40, 41-42, and >42 years of age were 8.2, 7.3, 5.5, 3.6, and 0.9
      %, respectively. In 10,076 cycles in which the male partner had a total motile
      sperm count >=5 million, the PRs in the respective age groups were 9.9, 8.6, 6.1,
      4.8, and 1.2 %. The largest-sized reported PRs for clomiphene citrate (CC)/IUI in
      the respective age groups were 11.5, 9.2, 7.3 4.3, and 1.0 % (4,199 cycles in
      total, Dovey et al., FertilSteril, 2008;90:2281-2286). There were no significant
      differences in PRs between unstimulated IUI and CC/IUI. CONCLUSION: PR for
      unstimulated IUI was similar to the reported PR for CC/IUI. Although this was a
      retrospective study without a control group, to reduce multiple pregnancy rate,
      we believe that unstimulated IUI is a reasonable treatment.

PMID- 25598698
TI  - Polyunsaturated fatty acids modify expression of TGF-beta in a co-culture model
      ultilising human colorectal cells and human peripheral blood mononuclear cells
      exposed to Lactobacillus gasseri, Escherichia coli and Staphylococcus aureus.
AB  - Commensal bacteria and polyunsaturated fatty acids (PUFAs) have both been shown
      independently to modulate immune responses. This study tested the hypothesis that
      the different colonic immunomodulatory responses to commensal (Lactobacillus
      gasseri) and pathogenic bacteria (Escherichia coli and Staphylococcus aureus) may
      be modified by PUFAs. Experiments used a Transwell system combining the
      colorectal cell line HT29, or its mucous secreting sub-clone HT29-MTX, with
      peripheral blood mononuclear cells to analyse immunomodulatory signalling in
      response to bacteria, with and without prior treatment with arachidonic acid,
      eicosapentaenoic acid or docosahexaenoic acid. L. gasseri increased transforming
      growth factor beta1 (TGF-beta1) mRNA and protein secretion in colonic cell lines
      when compared with controls, an effect that was enhanced by pre-treatment with
      eicosapentaenoic acid. In contrast, the Gram-negative pathogen E. coli LF82 had
      no significant effect on TGF-beta1 protein. L. gasseri also increased IL-8 mRNA
      but not protein while E. coli increased both; although differences between PUFA
      treatments were detected, none were significantly different to controls. Colonic
      epithelial cells show different immunomodulatory signalling patterns in response
      to the commensal L. gasseri compared to E. coli and S. aureus and pre-treatment
      of these cells with PUFAs can modify responses. Practical applications: We have
      demonstrated an interaction between dietary PUFAs and epithelial cell response to
      both commensal and pathogenic bacteria found in the gastrointestinal tract by
      utilising in vitro co-culture models. The data suggest that n-3 PUFAs may provide
      some protection against the potentially damaging effects of pathogens.
      Furthermore, the beneficial effects of combining n-3 PUFAs and the commensal
      bacteria, and potential probiotic, L. gasseri are illustrated by the increased
      expression of immunoregulatory TGF-beta1.

PMID- 25598700
TI  - Indonesian primary care physicians profile in 2011: Did practicing hours and
      conversion program for family medicine differentiate their services and
      continuing medical education activities?
AB  - BACKGROUND: In Indonesia, Family Medicine as a discipline is being developed
      through short courses since 12 years ago. A conversion program to become Family
      Physicians has been introduced recently. Among the 70,000 primary care physicians
      there are variety of practitioners, from new interns who start general practice
      to senior general practitioners. This study aims to describe the current
      Indonesian Primary Care Physicians (PCPs) profile which includes services
      provided and facilities as well as comparing the profile according to
      participation in the conversion program and practice hours. METHODS: A survey was
      carried out by using pre-tested, semi-structured and self-administered
      questionnaire among Indonesian primary care physicians (PCPs) who attended ASEAN
      Regional Primary Care Conference in Jakarta, November 2011. The survey elicited
      information regarding their practice environment, services provided, equipment,
      investigations provided, procedures, facilities and continuing medical education
      (CME) activities. RESULTS: Out of 240 PCPs participated, 65.4% (157/240) of them
      were family physicians and 67.1% (161/240) of them were full time practitioners
      (practice > 30 hours per week). Services like body mass index (BMI) measurement,
      substance abuse program, respiratory function test, mental health assessment, and
      cardiovascular assessment were provided by less than 50% of the PCPs as well as
      some investigations like electrocardiograph (ECG), proctoscopy, ultrasound,
      visual examination and funduscopy. Family Physicians significantly provided more
      house call services (77% vs 63%; p = 0.01), than those who are not. No other
      significant difference was found in the practice of the family physicians compare
      to non-family physicians. CONCLUSIONS: The Indonesian PCPs were lacking in the
      provision of some particular medical procedures, management and follows up of
      acute and chronic conditions, and preventive medicine and health education.
      Improvement of primary health care has been seen globally as necessary effort in
      health systems reform and this information could provide guidance toward the
      efforts to improve the quality of primary care physicians in Indonesia.

PMID- 25598701
TI  - In Situ Oxalic Acid Injection to Accelerate Arsenic Remediation at a Superfund
      Site in New Jersey.
AB  - Arsenic is a prevalent contaminant at a large number of US Superfund sites;
      establishing techniques that accelerate As remediation could benefit many sites.
      Hundreds of tons of As were released into the environment by the Vineland
      Chemical Co. in southern New Jersey during its manufacturing lifetime (1949
      1994), resulting in extensive contamination of surface and subsurface soils and
      sediments, groundwater, and the downstream watershed. Despite substantial
      intervention at this Superfund site, sufficient aquifer cleanup could require
      many decades if based on traditional pump and treat technologies only. Laboratory
      column experiments have suggested that oxalic acid addition to contaminated
      aquifer solids could promote significant As release from the solid phase. To
      evaluate the potential of chemical additions to increase As release in situ and
      boost treatment efficiency, a forced gradient pilot scale study was conducted on
      the Vineland site. During spring/summer 2009, oxalic acid and bromide tracer were
      injected into a small portion (~50 m2) of the site for 3 months. Groundwater
      samples indicate that introduction of oxalic acid led to increased As release.
      Between 2.9 and 3.6 kg of As were removed from the sampled wells as a result of
      the oxalic acid treatment during the 3-month injection. A comparison of As
      concentrations on sediment cores collected before and after treatment and
      analyzed using X-ray fluorescence spectroscopy suggested reduction in As
      concentrations of ~36% (median difference) to 48% (mean difference). While
      further study is necessary, the addition of oxalic acid shows potential for
      accelerating treatment of a highly contaminated site and decreasing the As
      remediation time-scale.

PMID- 25598702
TI  - Genetics and Personal Responsibility for Health.
AB  - Advances in genetic medicine may have implications for how we should think about
      personal responsibility for health, because they may show how it is possible to
      exert some control over risk factors that were previously thought as beyond the
      individual's control. Although we cannot control the genes that we are born with,
      we can often make decisions concerning genetic testing, disease prevention, and
      treatment. One might argue, therefore, that individuals should be treated as
      morally responsible for taking effective action in response to genetic risks
      factors, since genetically-based health risks are similar to other health risks.
      While this argument makes sense as an abstract, philosophical position, it is not
      a useful guide to public policy. Given these concerns, there is little society
      can or should do to encourage individuals to address their genetic risk factors,
      other than praising those who make prudent choices.

PMID- 25598703
TI  - Intrathecal injection of fluorocitric acid inhibits the activation of glial cells
      causing reduced mirror pain in rats.
AB  - BACKGROUND: Growing evidence has shown that unilateral nerve injury results in
      pain hypersensitivity in the ipsilateral and contralateral sides respective to
      the injury site. This phenomenon is known as mirror image pain (MIP). Glial cells
      have been indicated in the mechanism of MIP; however, it is not clear how glial
      cells are involved in MIP. METHODS: To observe phenomenon MIP and the following
      mechanism, 20 adult male Sprague-Dawley rats (weighing 180-220 g) were separated
      into two groups: Sham Group (n = 10) and left L5 spinal nerve ligated and
      sectioned (SNL) group (n = 10). Thermal hyperalgesia and mechanical
      hypersensitivity were measured for both groups to determine if the SNL model had
      Mirror image of Pain (MIP). Nav1.7 protein expression in DRG was analyzed using
      immunohistochemistry and western-blotting. And then to observe the effect of
      fluorocitrate on MIP, 15 rats were separated into three Groups: Sham Group (n =
      5); SNL + FC group: intrathecal injection of Fluorocitric acid(FC) 1 nmol/10 MUL
      (n = 5); SNL + NS group: intrathecal injection of 0.9% Normal Saline (n = 5).
      Behavior testing, immunocytochemistry, and western-blotting using dorsal root
      ganglion (DRG) from both sides were then conducted. RESULTS: The results showed
      pain hypersensitivity in both hind-paws of the SNL animals, Mechanical tests
      showed the paw withdrawal threshold dropped from 13.30 +/- 1.204 g to 2.57 +/-
      1.963 g at 14 d as will as the ipsilateral paw thermal withdrawal threshold
      dropped from 16.5 +/- 2.236 s to 4.38 +/- 2.544 s at 14 d. Mechanical tests
      showed the contralateral paw withdrawal threshold dropped from 14.01 +/- 1.412 to
      4.2 +/- 1.789 g at 7d will the thermal withdrawal threshold dropped from 16.8 +/-
      2.176 s to 7.6 +/- 1.517 s at 7d. Nav1.7 expression increased and glial cells
      actived in bilateral side DRG after SNL compared with sham group. After
      intrathecal injection of fluorocitrate, the glial cell in bilateral DRG were
      inhibited and the pain behavior were reversed in both hindpaws too. CONCLUSIONS:
      Fluorocitrate can inhibit the activation of glial cells in spinal cord and DRG,
      and reduce MIP.

PMID- 25598704
TI  - Construction and validation of the quality of oncology nursing care scale
      (QONCS).
AB  - BACKGROUND: There is scarcity of questionnaires specifically on the quality of
      the nursing care provided to patients diagnosed with cancer. The available
      questionnaires have been developed without attributing a holistic approach to the
      care provided with important patient's needs remaining without assessment. The
      main aim was to develop a self-administered cancer specific questionnaire
      exploring patients' views on quality nursing care provided in oncology settings.
      METHODS: The development of the scale proceeded through three phases. As part of
      the first development phase areas of concern and items of interest were
      identified through a literature review. The second phase included a pilot study
      of the QONCS and a subsequent validation phase through a multicentre study in 3
      hospitals, 4 departments and 418 patients diagnosed with cancer and receiving
      care as inpatients. The study was designed to select items, identify dimensions,
      measure reliability, content and construct validity. RESULTS: The QONCS consisted
      of 34 items. A factorial analysis grouped the items into five categories that
      define quality nursing care: a) Being supported and confirmed, b) Spiritual
      caring c) Sense of belonging, d) Being valued and e) Being respected. Cronbach's
      alpha was 0.95 for the entire questionnaire. The factor solution explained 68.53%
      of the variance. CONCLUSIONS: QONCS appears to measure with adequate reliability
      and validity the attributes of quality nursing care within the oncological
      settings and to patients with a variety of cancer diagnoses and at different
      phases of the cancer trajectory. The instrument is quick to disseminate and easy
      to complete, making it a suitable instrument for nursing professionals to
      evaluate patients' self-perceived quality of nursing care as a mean to promote
      the quality of the care provided in oncological settings.

PMID- 25598705
TI  - Associations between level of services integration and nurses' workplace well
      being.
AB  - BACKGROUND: To respond better to population needs, in recent years Quebec has
      invested in improving the integration of services and care pathways. Nurses are
      on the front lines of these transformation processes, which require them to adopt
      new clinical practices. This updating of practices can be a source of both
      satisfaction and stress. The aim of this study was to gain a better understanding
      of the relationship between the transformation processes underlying services
      integration and nurses' workplace well-being. METHOD: This study was based on a
      descriptive cross-sectional correlational design. The target population included
      all nurses working in four care pathways in a Quebec healthcare establishment:
      palliative oncology services, mental health services, autonomy support for the
      elderly, and chronic obstructive pulmonary disease. In all, 107 nurses took part
      in the study and completed a questionnaire sent to them. Hierarchical linear
      regression analyses were used to examine the relationship between level of
      integration, measured using the Development Model for Integrated Care; nurses'
      perceptions of organizational change, measured on four dimensions (challenge,
      responsibility, threat, control); and nurses' workplace well-being, measured on
      three dimensions (negative stress, positive stress, satisfaction), as defined by
      the Flexihealth model. RESULTS: Nurses in the palliative oncology care pathway,
      which was at a more advanced level of integration, presented a lower negative
      stress level and a higher positive stress level than did nurses in other care
      pathways. Their mean satisfaction score was also higher. More advanced
      integration was associated with nurses' feeling less threatened, as well as
      improved workplace well-being. The perception of threat appeared to be a
      significant mediating variable in the relationship between level of integration
      and well-being. CONCLUSION: The association observed between level of services
      integration and workplace well-being contributes to a better understanding of
      nurses' experiences in such situations. These results provide new perspectives on
      interventions that could be implemented to remedy the potential negative
      consequences of these types of transformations.

PMID- 25598706
TI  - Russian nursing students' knowledge level and attitudes in the context of human
      immunodeficiency virus (HIV) - a descriptive study.
AB  - BACKGROUND: The purpose of this study was to describe the knowledge of Russian
      nursing students regarding HIV and Acquired Immuno-Deficiency Syndrome (AIDS),
      and their attitudes towards caring for people/patients living with HIV or AIDS
      (PLWHA - People Living With HIV/AIDS) and their possible homophobic attitudes.
      The HIV epidemic in Russia is substantial and increasing rapidly. Hence this
      study provides important new information regarding this phenomenon. METHODS: The
      data was collected by questionnaire from students in three nursing schools (n =
      102, response rate 95.3%). The data was analyzed using PASW Statistics version
      18. For computing the level of the students' AIDS knowledge, all correct answers
      were recorded as equal to (1), while all incorrect and "Don't know" answers were
      recorded as equal to (0). Each respondent's scores were totaled and individual
      scores were analyzed using regression analysis. The effect of demographic
      variables on the average scores of attitudes was also subjected to regression
      analysis. RESULTS: Overall, students' knowledge level regarding HIV and AIDS was
      moderate (range 5-26). Of a maximum score of 33, the mean of correct answers was
      19.8 (SD = 3.70). Nursing students' attitudes were quite negative and they also
      demonstrated homophobic attitudes. The mean scale score for nursing students'
      general attitude was 2.75, and for homophobic attitudes it was 3.3 (min = 1, max
      = 5). Only the background factor of gender correlated with the homophobic level
      demonstrated (p = .05, beta = -.67). Nursing students' overall willingness to
      provide care for PLWHA was associated with their attitudes (p = .003, beta = 
      .534). CONCLUSIONS: Given that the HIV epidemic in Russia is both substantial and
      increasing, it is essential to improve HIV nursing education to provide
      sufficient and up-to-date information about HIV and also to prepare nursing
      students for caring for PLWHA. In doing so, this may help to address both the
      deficits in student knowledge, and also modify their attitude towards PLWHA.

PMID- 25598707
TI  - miRNA-146 negatively regulates the production of pro-inflammatory cytokines via
      NF-kappaB signalling in human gingival fibroblasts.
AB  - OBJECTIVE: In human gingival fibroblasts (HGFs), TLR4 recognises Pathogen
      associated molecular patterns (PAMPs), such as LPS, and subsequently activates
      downstream signals that lead to the production of pro-inflammatory cytokines. The
      aim of this study was to explore the mechanisms of LPS-induced miRNA-146
      regulation of TLR4 signals in HGFs. MATERIALS AND METHODS: HGFs were treated with
      Porphyromonas gingivalis (P.g) LPS, the cells were harvested, and kinase
      phosphorylation levels were detected by western blot. Selective pharmacological
      inhibitors and agonists were used to block or activate the relevant kinases,
      miRNA-146a/b expression levels were detected by real-time PCR, and IL-1, IL-6,
      and TNF-alpha production were measured by enzyme-linked immunosorbent assays
      (ELISA). A luciferase reporter plasmid containing miRNA-146a/b promoter was
      tested in terms of p50/p65 regulation. RESULTS: After P.g LPS treatment, NF
      kappaB and Erk1/2 were strongly activated in HGFs. miRNA-146a/b, IL-1, IL-6 and
      TNF-alpha levels were down-regulated when NF-kappaB inhibitor was used. p50/p65
      strongly activated miRNA-146a/b promoter as measured with the luciferase assay.
      CONCLUSION: In TLR4 signalling in HGFs, both miRNA-146a and miRNA-146b are
      downstream targets of NF-kappaB, but not of AP-1 signalling. miRNA-146a/b
      expression was specifically dependent on NF-kappaB but not Erk1/2 or JNK
      signalling.

PMID- 25598709
TI  - The Interplay between Media Use and Interpersonal Communication in the Context of
      Healthy Lifestyle Behaviors: Reinforcing or Substituting?
AB  - This study aims to explore how media use for health information and interpersonal
      health communication interact in the context of healthy lifestyle behaviors. This
      study hypothesizes that media use for health information and interpersonal health
      communication will serve as substitutes for one another. To test this hypothesis,
      this study uses a nationally representative survey of 2,107 civilian,
      noninstitutionalized adults in the United States. The results show that the
      associations between television use and Internet use and healthy lifestyle
      behaviors are enhanced among those who talk about health issues with their family
      and friends less frequently, which supports the substitution model. The
      implications that these findings have for future research are discussed.

PMID- 25598710
TI  - Exploring Socioeconomic Differences in Bedtime Behaviours and Sleep Duration in
      English Preschool Children.
AB  - Children's sleep is critical for optimal health and development; yet sleep
      duration has decreased in recent decades, and many children do not have adequate
      sleep. Certain sleep behaviours ('sleep hygiene') are commonly recommended, and
      there is some evidence that they are associated with longer nighttime sleep.
      Parents of 84 British 3-year-old children were interviewed about their children's
      sleep and completed five-night/four-day sleep diaries documenting their
      children's sleep, from which daily sleep duration was estimated. Diaries were
      validated by actigraphy in a subgroup of children. Sleep hygiene behaviours
      (regular bedtime, reading at bedtime, falling asleep in bed) were associated with
      each other, and were more common in the high socioeconomic status compared to the
      low socioeconomic status group. Parents' reasons for not practicing sleep hygiene
      included difficulty, inability or inconvenience. Sleep hygiene behaviours were
      associated with significantly longer child sleep at night but not over 24 h.
      Longer daytime napping compensated for shorter nighttime sleep in children whose
      parents did not implement sleep hygiene behaviours. Parents may need to be
      advised that certain behaviours are associated with longer nighttime sleep and
      given practical advice on how to implement these behaviours. (c) 2014 The
      Authors. Infant and Child Development published by John Wiley & Sons, Ltd.

PMID- 25598708
TI  - The combination of red palm oil and rooibos show anti-inflammatory effects in
      rats.
AB  - BACKGROUND: Red palm oil (RPO) and rooibos have been shown to exhibit
      cardioprotective properties. RPO is rich in essential fatty acids and fat soluble
      antioxidants while rooibos contains polyphenolic compounds with a unique
      composition of flavonoids. They exert their biological effects in different
      cellular compartments. Therefore the combination of these two natural food
      compounds has the potential to enhance the spectrum of available dietary
      antioxidants in different cellular compartments, which could result in an
      enhanced protection against certain pathological conditions such as inflammation.
      METHODS: Male Wistar rats weighing 150-200 g were supplemented with RPO, rooibos
      or their combination for 28 days. The Langendorff system and the lipoposaccharide
      (LPS)-induced inflammatory model were used to establish if RPO and rooibos, when
      supplemented alone or in combination, will reverse the negative effects of LPS on
      cardiac function at baseline. The effect of dietary intervention was also
      investigated on modulation of pro-inflammatory and anti-inflammatory cytokines in
      plasma and myocardial tissue. RESULTS AND DISCUSSION: The LPS resulted in
      induction of systemic inflammation as evidenced by increased levels of IL-1beta
      in plasma of LPS-treated rats compared to their non-treated control counterparts.
      Dietary supplementation and LPS treatment did not have an effect on baseline
      cardiac functional parameters. However, the elevation of IL-1beta levels in
      plasma of LPS-induced rats consuming either RPO or rooibos alone were paralleled
      with increased levels of the anti-inflammatory cytokine, IL-10. The combination
      of rooibos and RPO was associated with enhanced endogenous production of
      myocardial IL-10 in LPS-induced rats. CONCLUSION: The results of this study
      indicate that RPO and rooibos when supplemented individually showed anti
      inflammatory effect at systemic level while their combination exhibited an
      enhanced anti-inflammatory effect in the myocardial tissue. Therefore, the
      findings in the current study argue that the combination of these two natural
      food substances could be beneficial in clinically relevant conditions where
      inflammation plays a role.

PMID- 25598711
TI  - Rethinking the Clockwork of Work: Why Schedule Control May Pay Off at Work and at
      Home.
AB  - THE PROBLEM AND THE SOLUTION: Many employees face work-life conflicts and time
      deficits that negatively affect their health, well-being, effectiveness on the
      job, and organizational commitment. Many organizations have adopted flexible work
      arrangements but not all of them increase schedule control, that is, employees'
      control over when, where, and how much they work. This article describes some
      limitations of flexible work policies, proposes a conceptual model of how
      schedule control impacts work-life conflicts, and describes specific ways to
      increase employees' schedule control, including best practices for implementing
      common flexible work policies and Best Buy's innovative approach to creating a
      culture of schedule control.

PMID- 25598712
TI  - From the Editor's Desk.

PMID- 25598713
TI  - Letters to the editor.

PMID- 25598714
TI  - Advancing evidence-based practice - a quarterly compilation of research updates
      most likely to change clinical practice.

PMID- 25598715
TI  - Bioethics in practice - a quarterly column about medical ethics: ethical issues
      in organ allocation for transplantation - whose life is worth saving more?

PMID- 25598716
TI  - Clinical images - a quarterly column: emphysematous cystitis.

PMID- 25598717
TI  - Coronary heart disease risk factors: public impact of initial and later-announced
      risks.

PMID- 25598718
TI  - Fecal Microbiota Transplantation for Clostridium difficile Infection: The Ochsner
      Experience.
AB  - BACKGROUND: Clostridium difficile infection (CDI) accounts for 20%-30% of cases
      of antibiotic-associated diarrhea and is the most commonly recognized cause of
      infectious diarrhea in healthcare settings. The incidence of CDI is rising, while
      the effectiveness of antibiotics for treatment decreases with recurrent episodes.
      The use of fecal microbiota transplantation (FMT) for cure of CDI has been
      reported since 1958, and the worldwide cure rate is reported to be 93%. We report
      our experience with FMT for the treatment of CDI. METHODS: We performed a
      retrospective chart review of patients undergoing FMT for CDI at Ochsner Clinic
      Foundation from August 2012 to November 2013. FMT was administered via
      colonoscopy for patients with recurrent or severe CDI. Stool donors were screened
      for infections in the majority of cases. RESULTS: FMT was performed in 20 CDI
      patients. The 16 female and 4 male patients ranged in age from 27 to 89 years
      (mean 62 years). The average duration of illness from diagnosis to treatment was
      49.6 weeks, based on available data. Only 3 donors were unscreened for infectious
      pathogens. Nine donors were related to the recipients by blood; most of the other
      donors were spouses. The average length of follow-up after FMT was 3 months. No
      recurrences of CDI after treatment have been documented. Adverse events reported
      after treatment included abdominal cramping, bloating, flatulence, and nausea
      that resolved. CONCLUSION: Although the US Food and Drug Administration currently
      considers FMT an experimental therapy, we demonstrate that FMT is safe, well
      tolerated, and effective for recurrent and severe CDI.

PMID- 25598719
TI  - Nurse practitioners and physician assistants: preparing new providers for
      hospital medicine at the mayo clinic.
AB  - BACKGROUND: Hospital medicine is a growing field with an increasing demand for
      additional healthcare providers, especially in the face of an aging population.
      Reductions in resident duty hours, coupled with a continued deficit of medical
      school graduates to appropriately meet the demand, require an additional
      workforce to counter the shortage. A major dilemma of incorporating nonphysician
      providers such as nurse practitioners and physician assistants (NPPAs) into a
      hospital medicine practice is their varying academic backgrounds and inpatient
      care experiences. Medical institutions seeking to add NPPAs to their hospital
      medicine practice need a structured orientation program and ongoing NPPA
      educational support. METHODS: This article outlines an NPPA orientation and
      training program within the Division of Hospital Internal Medicine (HIM) at the
      Mayo Clinic in Rochester, MN. RESULTS: In addition to a practical orientation
      program that other institutions can model and implement, the division of HIM also
      developed supplemental learning modalities to maintain ongoing NPPA competencies
      and fill learning gaps, including a formal NPPA hospital medicine continuing
      medical education (CME) course, an NPPA simulation-based boot camp, and the first
      hospital-based NPPA grand rounds offering CME credit. Since the NPPA orientation
      and training program was implemented, NPPAs within the division of HIM have
      gained a reputation for possessing a strong clinical skill set coupled with a
      depth of knowledge in hospital medicine. CONCLUSION: The NPPA-physician model
      serves as an alternative care practice, and we believe that with the institution
      of modalities, including a structured orientation program, didactic support,
      hands-on learning, and professional growth opportunities, NPPAs are capable of
      fulfilling the gap created by provider shortages and resident duty hour
      restrictions. Additionally, the use of NPPAs in hospital medicine allows for
      patient care continuity that is otherwise missing with resident practice models.

PMID- 25598720
TI  - Using second life to facilitate peer storytelling for grieving oncology nurses.
AB  - BACKGROUND: Oncology nurses often experience intense emotional reactions to
      patient deaths but may be forced to ignore or hide their feelings because of work
      related responsibilities. The complexity of nurses' work and personal lives
      creates obstacles for participating in traditional support groups where grieving
      nurses can bond and share. We hypothesized that using a web-based, three
      dimensional (3-D) virtual world technology (Second Life) may provide a venue to
      facilitate peer storytelling to support nurses dealing with grief. METHODS: We
      used a mixed-methods approach involving focus groups and surveys to explore the
      use of peer storytelling for grieving oncology nurses. Nine acute and ambulatory
      oncology nurses in groups of 3 participated using avatars in 5 group moderator
      guided sessions lasting 1 hour each in a private 3-D outdoor virtual meeting
      space within Second Life. Baseline information was collected using a 12-item
      demographic and professional loss survey. At the end of the study, a 20-item
      survey was administered to measure professional losses during the study, exchange
      of support during sessions, and meaning-making and to evaluate peer storytelling
      using Second Life. RESULTS: Overall, nurses reported peer storytelling sessions
      in Second Life were helpful in making sense of and in identifying a benefit of
      their grief experience. They felt supported by both the group moderator and group
      members and were able to personally support group members during storytelling.
      Although nurses reported Second Life was helpful in facilitating storytelling
      sessions and expressed overall satisfaction with using Second Life, open-ended
      comments registered difficulties encountered, mostly with technology. Three
      central themes emerged in sessions, representing a dynamic relationship between
      mental, spiritual, and emotional-behavioral responses to grief: cognitive
      readiness to learn about death, death really takes death experience, and
      emotional resilience. CONCLUSION: This study suggests a potential benefit in
      using peer storytelling sessions in Second Life to facilitate oncology nurses'
      grief resolution. In particular, Second Life provides a nonthreatening venue for
      participating nurses to share their innermost feelings and accrue their own
      inventory of stories. Through these stories, each nurse's relational experience
      in expressing and coping with grief is realized.

PMID- 25598721
TI  - Developing a Standardized and Sustainable Resident Sign-Out Process: An AIAMC
      National Initiative IV Project.
AB  - BACKGROUND: Duty hour restrictions imposed upon training physicians have led to
      increased handoffs and the potential for discontinuity in patient care. Research
      has demonstrated a significant opportunity for decreasing errors with a
      standardized handoff process. Thus, we designed a project to implement a
      standardized approach to handoffs, specifically resident-to-resident handoffs.
      METHODS: We performed an initial assessment of the tools, practices, and policies
      currently in use to facilitate handoffs institutionally. Subsequently, we created
      a template within our electronic medical record and paired it with a verbal
      handoff process. We developed a plan to build department champions to disseminate
      information and provide mentorship. We intend to evaluate this process at
      designated intervals to ensure sustainability. RESULTS: Survey results were
      obtained from 45 faculty and 61 residents from a wide representation of
      specialties. We found that although a subjective sense of satisfaction was
      present, there was substantial variability between processes. Seventy-two percent
      of faculty reported at least once identifying a patient safety issue that
      occurred as a result of the handoff process, but 77% of faculty sometimes or
      never supervised the process. Eighty percent of residents reported sometimes or
      never receiving feedback on their handoffs. CONCLUSIONS: Based on medicine's
      evolving environment and an apparent opportunity to optimize resident training
      and patient safety, we developed a plan to standardize, implement, and evaluate
      resident handoffs within our system. The results thus far have resulted in a gap
      analysis that will serve as the basis for reporting finalized data at the
      conclusion of this prospective study.

PMID- 25598722
TI  - Systolic heart failure: knowledge gaps, misconceptions, and future directions.
AB  - BACKGROUND: Systolic heart failure is the final manifestation of several
      cardiovascular conditions. The 2001 American College of Cardiology/American Heart
      Association guidelines depicting the progression of heart failure (HF) from stage
      A through stage D are aimed at the early treatment of risk factors. However,
      treatment is often delayed until stage C, and as a result HF continues to impose
      a major burden on our healthcare industry. METHODS: We conducted an extensive
      literature review of the MEDLINE/PubMed database with the purpose of elucidating
      knowledge gaps and misconceptions regarding systolic HF. RESULTS: Long-term beta
      adrenergic blocking is the only pharmacologic intervention that reverses left
      ventricular remodeling. Whether beta adrenergic blocking prevents or delays left
      ventricular remodeling in patients at risk of HF is presently unknown. A
      knowledge gap also exists regarding the phenotype of patients that derives a
      mortality benefit from implantable cardioverter defibrillator therapy. Acute
      decompensated HF is a misnomer because patients with chronic HF are known to be
      deteriorating in the weeks preceding hospitalization. Functional class and
      ejection fraction are not closely correlated. Advanced HF therapies such as heart
      transplantation and mechanical circulatory support are available to an extremely
      small fraction of patients with systolic HF. CONCLUSION: Concentrating efforts on
      the early stages of the disease process with optimal management of risk factors
      for HF is critical to having a significant impact on this ongoing pandemic.

PMID- 25598723
TI  - Systematic review of interventions to repair ascending aortic pseudoaneurysms.
AB  - BACKGROUND: The safety and efficacy of endovascular therapies for ascending
      aortic pseudoaneurysms (AAPs) are still controversial. METHODS: We report an
      endovascular correction of an AAP in a high-risk surgical patient and present the
      results of a literature review focusing on AAP treatment strategies. A
      multilingual search of AAP therapy was performed with limiting dates of January
      1980 to May 2014. The studies were classified by intervention. RESULTS: A 79-year
      old male with a 9 * 10 * 7 cm AAP in the anterior mediastinum was considered too
      high risk for surgery. An endovascular closure with a 12 mm Amplatzer septal
      occluder device (St. Jude Medical) was performed, and computed tomography
      angiography at 3-month follow-up exhibited a thrombosed AAP with minimal residual
      shunt. In our literature search, we identified 355 cases of AAPs, mostly case
      reports (91.5%) and a few patient series (8.5%). Surgical correction accounted
      for 73.8% of the cases, 5% of the patients were conservatively treated or
      considered too critically ill for any intervention, and 21.2% were treated with
      endovascular techniques. The most commonly reported endovascular techniques were
      stent grafts (9.8%) and septal occluder devices (9.8%). CONCLUSION: Although
      endovascular closure of AAPs with off-label devices is a reliable option for
      controlling the expansion and symptoms in high-risk surgical patients, solid data
      on survival are lacking. Efforts to promote discussion within the heart team to
      expand the application of endovascular techniques can provide groundbreaking
      evidence to support the use of endovascular techniques as guideline therapy when
      facing these complicated cases.

PMID- 25598724
TI  - Current trends in supraventricular tachycardia management.
AB  - BACKGROUND: Supraventricular tachycardia (SVT) is a general term describing a
      group of arrhythmias whose mechanism involves or is above the atrioventricular
      node. The mechanisms of most forms of SVT have been elucidated, and pharmacologic
      and invasive therapies have evolved simultaneously. METHODS: We provide a brief
      overview of the mechanisms, classifications, and electrocardiographic
      characteristics of different SVTs and describe current trends in noninvasive and
      invasive therapies. RESULTS: The term SVT encompasses a heterogeneous group of
      arrhythmias with different electrophysiologic characteristics. Knowledge of the
      mechanism of each SVT is important in determining management at the bedside and
      in the electrophysiology laboratory. CONCLUSION: In the acute setting, vagal
      maneuvers and pharmacologic therapy can be effective in arrhythmia termination.
      Catheter-based radiofrequency ablation has revolutionized therapy for many SVTs,
      and newer techniques have significantly improved ablation efficacy and reduced
      periprocedural complications and procedure times. Cryoablation is currently being
      investigated as an alternative form of energy delivery, although the long-term
      effectiveness of this procedure currently limits its use for many SVTs.

PMID- 25598725
TI  - Cardiac resynchronization therapy: history, present status, and future
      directions.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is one of the most exciting
      recent advancements in heart failure (HF) treatment. METHODS: This review surveys
      the available literature regarding the effectiveness of CRT in treating patients
      with HF. RESULTS: By targeting ventricular dyssynchrony, CRT attempts to give the
      failing heart a mechanical advantage that can substantially improve both symptoms
      and mortality. CONCLUSION: CRT results in short-term and long-term improvement in
      cardiac structure and function, often leading to enhanced quality of life and,
      for some patients, enhanced survival.

PMID- 25598726
TI  - Future management of carotid stenosis: role of urgent carotid interventions in
      the acutely symptomatic carotid patient and best medical therapy for asymptomatic
      carotid disease.
AB  - BACKGROUND: Stroke is the fourth leading cause of death in the United States,
      leading to devastating disability. Most strokes are ischemic, and nearly one
      third of these are caused by carotid disease. The primary mechanism of carotid
      related stroke is an atheroembolic event from an unstable atherosclerotic plaque
      rupture. In the 1990s, randomized trials demonstrated the benefit of carotid
      endarterectomy (CEA) in reducing the risk of stroke in both symptomatic and
      asymptomatic carotid disease. METHODS: We review best medical therapy (BMT) for
      asymptomatic carotid disease and recent randomized trials comparing CEA and
      carotid angioplasty stenting (CAS), and we discuss the role of urgent carotid
      interventions in patients with acute neurologic symptoms. RESULTS: In 2010, 2
      large trials demonstrated the efficacy of CAS in select patients, although CAS
      was associated with an increased procedural stroke risk compared to CEA. An age
      effect was observed; patients >75 years do worse with CAS compared to CEA. As BMT
      has evolved in the past decade, a future trial (CREST-2) will address whether BMT
      is equal to intervention (CEA or CAS) in asymptomatic carotid disease. In a
      subgroup of patients with asymptomatic carotid disease, CEA plus BMT will likely
      remain the mainstay therapy for carotid disease compared to BMT alone. CEA and
      CAS will continue to play complementary roles in the future, as CAS will be done
      in select patients in whom CEA cannot be undertaken because of high-risk
      anatomical or medical conditions. Finally, a role for urgent carotid
      interventions in a select group of patients who present with acute neurologic
      symptoms is developing as a way to prevent recurrent stroke after an initial
      carotid plaque rupture event. CONCLUSION: CAS has an increasingly higher risk of
      stroke with advancing age. Patients treated with CAS have a 1.76-fold increased
      risk of stroke (95% CI, 1.35-2.31) with each 10-year increase in age. No such age
      effect is seen in patients treated with CEA. Age is a critical variable in making
      informed choices regarding treatment of severe carotid artery stenosis.

PMID- 25598729
TI  - Lung transplantation: an overview of candidacy and outcomes.
AB  - BACKGROUND: Various factors must be taken into account when considering lung
      transplantation, including candidacy, contraindications, and outcomes. METHODS:
      This article presents a review of the data and literature on lung
      transplantation, tracking the evolution of the treatment as it applies to
      different conditions, as well as an examination of patient survival rates in
      relation to pathology and treatment. RESULTS: Timely referral and careful
      selection of candidates for lung transplantation maximize the outcomes of the
      procedure, resulting in a longer lifespan with improved physical health for
      patients. CONCLUSION: Lung transplantation is a therapeutic option for patients
      with various lung diseases. Adapting treatment options and follow-up treatment to
      the individual patient's lifestyle and pathology optimizes patient survival rates
      after transplantation.

PMID- 25598728
TI  - Deep Venous Thrombosis: An Interventionalist's Approach.
AB  - BACKGROUND: Deep venous thrombosis (DVT) of the lower extremity has traditionally
      been anatomically categorized into proximal DVT (thrombosis involving the
      popliteal vein and above) and distal DVT (isolated calf vein thrombosis).
      Proximal DVT involving the common femoral and/or iliac veins, referred to as
      iliofemoral DVT (IFDVT), represents a disease process with a worse prognosis and
      higher risk for poor clinical outcomes compared to proximal DVT not involving the
      common femoral or iliac draining veins. METHODS: This review discusses
      therapeutic options for treatment of lower extremity IFDVT, including adjuvant
      anticoagulation and catheter-based invasive therapies; literature supporting
      current acute interventional techniques; and the recommendations from the
      recently published American Heart Association guidelines. RESULTS: Patients with
      IFDVT represent an opportune subset of patients for acute interventional
      management with currently available techniques. This subset of patients with
      proximal DVT has a worse prognosis, is less well studied, and benefits more from
      acute intervention compared to patients with proximal DVT or distal DVT.
      CONCLUSION: Invasive catheter-based therapies that remove thrombus and correct
      venous outflow obstructions improve outcomes and morbidity in patients with
      IFDVT. Future trials that address IFDVT specifically will improve our
      understanding and the proper management of this higher-risk subset of patients
      with DVT.

PMID- 25598727
TI  - Cardiovascular safety profile of currently available diabetic drugs.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
      mortality among patients with diabetes, underscoring the importance of choosing
      drugs that do not increase cardiovascular risk and reduce the risk of
      cardiovascular events. Since 2008, the US Food and Drug Administration has
      recommended that new drugs for type 2 diabetes undergo clinical trials to
      demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, the
      European Medicines Agency issued a similar recommendation. METHODS: We searched
      the PubMed, Cochrane CENTRAL, EMBASE, and CINAHL databases from inception through
      August 2013 and compiled and reviewed the existing data on the cardiovascular
      safety profiles of currently available diabetic drugs. RESULTS: While intensive
      glycemic control in diabetics has been consistently shown to reduce the risk of
      microvascular complications, the data on macrovascular risk reduction have not
      been as clear, and questions have been raised about possible increases in
      cardiovascular morbidity and mortality. CONCLUSION: Careful selection of drug
      therapy-paying particular attention to cardiovascular safety-is important in
      optimizing diabetic therapy.

PMID- 25598730
TI  - Pneumonia readmissions: risk factors and implications.
AB  - BACKGROUND: Pneumonia continues to be a severe health problem in the United
      States, responsible for close to 1 million hospital admissions and nearly 140,000
      hospital readmissions per year. The literature on this topic suggests that
      approximately 1 in 5 patients with pneumonia is readmitted to the hospital within
      30 days of discharge and that most readmissions are not because of pneumonia
      related causes. METHODS: Although many pneumonia readmissions may not be
      preventable, reducing readmissions is feasible, as shown by recent trends in
      Centers for Medicare & Medicaid Services data. RESULTS: Modifiable patient-,
      physician-, and system-related factors can be targeted for intervention.
      CONCLUSION: Many interventions aimed at reducing hospital readmissions targeting
      transitional care, care coordination, and postdischarge care have shown potential
      for reducing readmission rates.

PMID- 25598732
TI  - Hepatitis C screening.
AB  - BACKGROUND: Hepatitis C screening is now recommended for all individuals born
      between the years 1945-1965 in addition to individuals who have high-risk
      factors. Although most clinicians have extensive experience with the diagnosis
      and treatment of the disease, they have limited experience screening for it.
      METHODS: We report current screening guidelines and methods. RESULTS: By
      identifying the disease as early as possible, screening and treatment can reduce
      morbidity and mortality. CONCLUSION: Screening for hepatitis C leads to the
      appropriate evaluation and treatment of individuals chronically infected with the
      hepatitis C virus and prevents the progression of liver disease to cirrhosis,
      hepatocellular carcinoma, and the associated morbidity and mortality. Screening
      for hepatitis C is also cost effective.

PMID- 25598731
TI  - Acute hypertension: a systematic review and appraisal of guidelines.
AB  - BACKGROUND: Few clinical practice guidelines provide management recommendations
      for acute hypertensive episodes except in the context of specific conditions such
      as pregnancy and stroke. METHODS: We performed a systematic search to identify
      guidelines addressing acute hypertension and appraised the guidelines using the
      Appraisal of Guidelines for Research and Evaluation (AGREE II) validated quality
      assessment tool. Two reviewers independently appraised and one extracted key
      recommendations. Literature on secondary hypertension, hypertension in pregnancy,
      preeclampsia/eclampsia, stroke, aortic dissection, and pheochromocytoma was
      excluded. RESULTS: Three guidelines were identified, sponsored by the American
      College of Emergency Physicians (ACEP), the National Heart, Lung, and Blood
      Institute (NHLBI), and the European Society of Hypertension (ESH) in conjunction
      with the European Society of Cardiology (ESC). AGREE II yielded mean domain (%)
      and overall assessment scores (1-7) as follows: NHLBI: 73%, 5.5; ACEP: 67%, 5.5;
      and ESH/ESC: 56%, 4.5. In hypertensive emergencies, the NHLBI guideline
      recommends reducing mean arterial pressure by <=25% for the first hour, and then
      to 160/100-110 mmHg by 2-6 hours with subsequent gradual normalization in 24-48
      hours. The ESH/ESC has similar recommendations. The ACEP does not address
      guidelines for hypertensive emergency but focuses on whether screening for target
      organ damage or medical intervention in patients with asymptomatic elevated blood
      pressure in emergency departments reduces the rate of adverse outcomes,
      concluding that routine screening does not reduce adverse outcomes, but patients
      with poor follow-up may benefit from routine screening. CONCLUSION: NHLBI and
      ESH/ESC guidelines are high quality and provide similar recommendations for
      management of asymptomatic acute hypertensive episodes and hypertensive
      emergencies. Additional research is needed to inform clinical practice guidelines
      for this common condition.

PMID- 25598733
TI  - Familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant-inherited
      genetic disorder that leads to elevated blood cholesterol levels. FH may present
      as severely elevated total cholesterol and low density lipoprotein (LDL)
      cholesterol levels or as premature coronary heart disease (CHD). METHODS: This
      review presents information on the disease and on the effects of drug treatment
      and lifestyle changes. RESULTS: Routine lipid testing should identify most
      patients with FH. Once an index case is identified, testing should be offered to
      family members. Early diagnosis and aggressive treatment with therapeutic
      lifestyle changes and statins can prevent premature CHD and other atherosclerotic
      sequelae in patients with FH. CONCLUSION: Emerging therapies such as LDL
      apheresis and novel therapeutic agents may be useful in patients with homozygous
      FH or treatment-resistant FH. Liver transplantation is the only effective therapy
      for severe cases of homozygous FH.

PMID- 25598734
TI  - Thirty years of intracrinology.
AB  - BACKGROUND: Intracrinology is the study of the intracellular actions, regulation,
      trafficking, and interactions of extracellular signaling peptides/proteins.
      METHODS: We describe the development of intracrine biology since the term was
      defined in 1984. RESULTS: Intracrine biology plays a role in many normal and
      pathological processes and represents a fertile field for the development of
      novel therapeutics. CONCLUSION: Although 30 years old, the field of
      intracrinology is only now becoming widely accepted. Intracrine principles can be
      applied to the investigation of physiological processes and to the development of
      new therapies.

PMID- 25598737
TI  - Primary palliative care for the general internist: integrating goals of care
      discussions into the outpatient setting.
AB  - BACKGROUND: Primary palliative care consists of the palliative care competencies
      required of all primary care clinicians. Included in these competencies is the
      ability to assist patients and their families in establishing appropriate goals
      of care. Goals of care help patients and their families understand the patient's
      illness and its trajectory and facilitate medical care decisions consistent with
      the patient's values and goals. General internists and family medicine physicians
      in primary care are central to getting patients to articulate their goals of care
      and to have these documented in the medical record. CASE REPORT: Here we present
      the case of a 71-year-old male patient with chronic obstructive pulmonary
      disorder, congestive heart failure, and newly diagnosed Alzheimer dementia to
      model pertinent end-of-life care communication and discuss practical tips on how
      to incorporate it into practice. CONCLUSION: General internists and family
      medicine practitioners in primary care are central to eliciting patients' goals
      of care and achieving optimal end-of-life outcomes for their patients.

PMID- 25598735
TI  - Functional genomics in the study of mind-body therapies.
AB  - BACKGROUND: Mind-body therapies (MBTs) are used throughout the world in
      treatment, disease prevention, and health promotion. However, the mechanisms by
      which MBTs exert their positive effects are not well understood. Investigations
      into MBTs using functional genomics have revolutionized the understanding of MBT
      mechanisms and their effects on human physiology. METHODS: We searched the
      literature for the effects of MBTs on functional genomics determinants using
      MEDLINE, supplemented by a manual search of additional journals and a reference
      list review. RESULTS: We reviewed 15 trials that measured global or targeted
      transcriptomic, epigenomic, or proteomic changes in peripheral blood. Sample
      sizes ranged from small pilot studies (n=2) to large trials (n=500). While the
      reliability of individual genes from trial to trial was often inconsistent, genes
      related to inflammatory response, particularly those involved in the nuclear
      factor-kappa B (NF-kappaB) pathway, were consistently downregulated across most
      studies. CONCLUSION: In general, existing trials focusing on gene expression
      changes brought about by MBTs have revealed intriguing connections to the immune
      system through the NF-kappaB cascade, to telomere maintenance, and to apoptotic
      regulation. However, these findings are limited to a small number of trials and
      relatively small sample sizes. More rigorous randomized controlled trials of
      healthy subjects and specific disease states are warranted. Future research
      should investigate functional genomics areas both upstream and downstream of MBT
      related gene expression changes-from epigenomics to proteomics and metabolomics.

PMID- 25598736
TI  - Meditation and coronary heart disease: a review of the current clinical evidence.
AB  - BACKGROUND: Chest pain from coronary heart disease (CHD) accounts for more than 8
      million emergency department visits every year in the United States, emphasizing
      the need for cardiovascular (CV) interventions to help reduce this high number.
      Meditation--a state of contemplation, concentration, and reflection--has the
      potential to help decrease CV disease. METHODS: This article reviews the
      available data regarding the effects of meditation on various aspects of CV
      health. RESULTS: During the past few decades, multiple studies have demonstrated
      the beneficial effects of meditation on various CV risk factors. In addition to
      decreasing CV mortality, meditation has also been shown to improve conditions
      such as hypertension, type 2 diabetes mellitus, dyslipidemia, and high cortisol
      levels. Still unclear is how current medical therapies impact overall CHD in
      comparison to meditation techniques. CONCLUSION: Prospective trials are needed to
      study the effects of meditation on CV risk factors, to provide guidelines for
      daily meditation practice, and to determine the efficacy of meditation compared
      to current pharmacologic therapies.

PMID- 25598739
TI  - The louisiana clinical data research network: leveraging regional and national
      resources to improve clinical research efficiency.
AB  - BACKGROUND: Mapping of the human genome and technological advancements allowing
      storage and rapid retrieval of healthcare data have heralded a new phase in
      clinical medicine and have served as a catalyst for the advent of personalized
      medicine. The use of health information databases provides a unique opportunity
      to investigate questions of great complexity and real-world application in a way
      that is most useful in providing high quality, safe, and cost-effective clinical
      care to patients. METHODS: The Louisiana Clinical Data Research Network (LACDRN)
      aims to streamline the workflow of multiinstitutional clinical studies and to
      dramatically expand the clinical research resources available to local
      investigators. The LACDRN contains health information for more than 1 million
      patients in Southeast Louisiana and is a rich resource for researchers to conduct
      retrospective or observational trials and to recruit patients for prospective
      studies. RESULTS: The LACDRN is part of a large-scale initiative by the Patient
      Centered Outcomes Research Institute to create a national electronic health
      record network that enables the timely initiation and completion of comparative
      effectiveness research in a coordinated effort. For the first time, network
      research will be guided in part by input from patients and caregivers, increasing
      their engagement in the research process. CONCLUSION: The establishment of the
      LACDRN is a unique opportunity for clinicians to take part in an innovative
      national initiative designed to offer new clinical research options for patients
      and to carry out cutting-edge translational, clinical, and health services
      research.

PMID- 25598738
TI  - Difficult conversations: from diagnosis to death.
AB  - BACKGROUND: Communication is the cornerstone of good multidisciplinary medical
      care, and the impact of conversations about diagnosis, treatment, and prognosis
      is indisputable. Healthcare providers must be able to have difficult
      conversations that accurately describe diagnostic procedures, treatment goals,
      and the benefits and/or risks involved. METHODS: This paper reviews the
      literature about the importance of communication in delivering bad news, the
      status of communication training, communication strategies, and psychosocial
      interventions. RESULTS: Although many published guidelines address difficult
      communication, communication training is lacking. Consequently, many clinicians
      may have difficulties with, or in the worst-case scenario, avoid delivering bad
      news and discussing end-of-life treatment. Clinicians also struggle with how to
      have the last conversation with a patient and how to support patient autonomy
      when they disagree with a patient's choices. CONCLUSION: There is a clinical
      imperative to educate physicians and other healthcare workers on how to
      effectively deliver information about a patient's health status, diagnostic
      avenues to be explored, and decisions to be made at critical health junctions.
      Knowing how to implement the most rudimentary techniques of motivational
      interviewing, solution-focused brief therapy, and cognitive behavioral therapy
      can help physicians facilitate conversations of the most difficult type to
      generate positive change in patients and families and to help them make decisions
      that minimize end-of-life distress.

PMID- 25598742
TI  - Aggregation of Calcium Phosphate and Oxalate Phases in the Formation of Renal
      Stones.
AB  - The majority of human kidney stones are comprised of multiple calcium oxalate
      monohydrate (COM) crystals encasing a calcium phosphate nucleus. The
      physiochemical mechanism of nephrolithiasis has not been well determined on the
      molecular level; this is crucial to the control and prevention of renal stone
      formation. This work investigates the role of phosphate ions on the formation of
      calcium oxalate stones; recent work has identified amorphous calcium phosphate
      (ACP) as a rapidly forming initial precursor to the formation of calcium
      phosphate minerals in vivo. The effect of phosphate on the nucleation of COM has
      been investigated using the constant composition (CC) method in combination with
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
      Our findings indicate COM nucleation is strongly promoted by the presence of
      phosphate; this occurs at relatively low phosphate concentrations, undersaturated
      with respect to brushite (dicalcium phosphate dehydrate, DCPD) formation. The
      results show that ACP plays a crucial role in the nucleation of calcium oxalate
      stones by promoting the aggregation of amorphous calcium oxalate (ACO) precursors
      at early induction times. The coaggregations of ACP and ACO precursors induce the
      multiple-point nucleation of COM. These novel findings expand our knowledge of
      urinary stone development, providing potential targets for treating the condition
      at the molecular level.

PMID- 25598741
TI  - Epitaxial Retrieval of a Disappearing Polymorph.
AB  - Recrystallization of [PdCl2([9]aneS2O)] ([9]aneS2O = 1-oxa-4,7
      dithiacyclononane), 1, and [PtCl2([9]aneS2O)], 2, by diffusion of Et2O vapor into
      solutions of the complexes in MeNO2 yielded three phases of 1 and two phases of
      2. The known phase of 1, herein designated alpha-1, was obtained under ambient
      conditions. A second phase, designated beta-1, was initially also obtained by
      this method; however, following the advent of a third phase, gamma-1, all
      subsequent efforts over a period of a year to crystallize beta-1 yielded either
      gamma-1, obtained by carrying out the recrystallization at elevated temperature,
      or alpha-1, commonly found throughout the study. This persistent absence of a
      phase which could initially be crystallized with ease led us to the conclusion
      that beta-1 was an example of a "disappearing polymorph". The first phase
      obtained of 2, designated alpha-2, was obtained by recrystallization under
      ambient conditions and is isomorphous and isostructural with alpha-1. The second
      phase beta-2 was obtained by slight elevation of the recrystallization
      temperature and was found to be isomorphous and isostructural with beta-1.
      Subsequently, beta-2 was used to seed the growth of the disappearing polymorph
      beta-1. No third phase of 2 (gamma-2) has been isolated thus far.

PMID- 25598745
TI  - Massively Multithreaded Maxflow for Image Segmentation on the Cray XMT-2.
AB  - Image segmentation is a very important step in the computerized analysis of
      digital images. The maxflow mincut approach has been successfully used to obtain
      minimum energy segmentations of images in many fields. Classical algorithms for
      maxflow in networks do not directly lend themselves to efficient parallel
      implementations on contemporary parallel processors. We present the results of an
      implementation of Goldberg-Tarjan preflow-push algorithm on the Cray XMT-2
      massively multithreaded supercomputer. This machine has hardware support for 128
      threads in each physical processor, a uniformly accessible shared memory of up to
      4 TB and hardware synchronization for each 64 bit word. It is thus well-suited to
      the parallelization of graph theoretic algorithms, such as preflow-push. We
      describe the implementation of the preflow-push code on the XMT-2 and present the
      results of timing experiments on a series of synthetically generated as well as
      real images. Our results indicate very good performance on large images and pave
      the way for practical applications of this machine architecture for image
      analysis in a production setting. The largest images we have run are 320002
      pixels in size, which are well beyond the largest previously reported in the
      literature.

PMID- 25598740
TI  - Recent publications by ochsner authors.

PMID- 25598744
TI  - The Role of the Social Environment in Alcohol or Drug Relapse of Probationers
      Recently Released from Jail.
AB  - OBJECTIVES: Many individuals involved with the criminal justice system also meet
      criteria for a substance use disorder. Social support has been identified as an
      important factor in alcohol and drug relapse, and also for individuals who are
      incarcerated. The purposes of this study were to describe personal
      characteristics and the social networks of adult male probationers with substance
      use disorders and test how changes in social networks related to alcohol or drug
      use after release from jail. METHODS: Fifty adult male probationers who were
      recently incarcerated (60 to 210 days prior to screening) were recruited from a
      large Southwest Probation and Parole Division office, and were administered a
      single assessment that assessed demographic information, social networks, and
      quantity and frequency of alcohol and drug use before and after incarceration.
      RESULTS: In this sample there was an over-representation of ethnic minorities,
      higher rates of unemployment, lower educational levels, and lower median income
      than national averages. Results showed that there were significant changes in
      social networks from pre- to post-incarceration. Additionally, changes in social
      networks significantly predicted substance use after release from jail, even
      after controlling for substance use prior to incarceration, and the percentage of
      social network members who were heavy drug users mediated percent days abstinent
      from alcohol and drugs from pre- to post-incarceration. CONCLUSIONS: Social
      networks and social support may operate as dynamic factors in relapse, and may be
      a target for intervention for adult males with substance use disorders being
      released from jail.

PMID- 25598743
TI  - Transcranial Magnetic Stimulation and Deep Brain Stimulation in the treatment of
      alcohol dependence.
AB  - Alcohol dependence is a major social, economic, and public health problem.
      Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular,
      and respiratory systems and it can be lethal, costing hundreds of billions to the
      health care system. Despite the existence of cognitive-behavioral therapy,
      psychosocial interventions, and spiritually integrated treatment to treat it,
      alcohol dependence has a high relapse rate and poor prognosis, albeit with high
      interindividual variability. In this review, we discuss the use of two
      neuromodulation techniques, namely repetitive transcranial magnetic stimulation
      (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages
      compared to first-line pharmacological treatment for alcohol dependence. We also
      discuss rTMS and DBS targets for alcohol dependence treatment, considering
      experimental animal and human evidence, with careful consideration of
      methodological issues preventing the identification of feasible targets for
      neuromodulation treatments, as well as inter-individual variability factors
      influencing alcoholism prognosis. Lastly, we anticipate future research aiming to
      tailor the treatment to each individual patient by combining neurofunctional,
      neuroanatomical and neurodisruptive techniques optimizing the outcome.

PMID- 25598746
TI  - Expanding medication options for pediatric ADHD.

PMID- 25598747
TI  - Formation and stabilization of persistent free radicals.
AB  - We demonstrate that stable and relatively unreactive "environmentally persistent
      free radicals (PFRs)" can be readily formed in the post-flame and cool-zone
      regions of combustion systems and other thermal processes. These resonance
      stabilized radicals, including semiquinones, phenoxyls, and cyclopentadienyls,
      can be formed by the thermal decomposition of molecular precursors including
      catechols, hydroquinones and phenols. Association with the surfaces of fine
      particles imparts additional stabilization to these radicals such that they can
      persist almost indefinitely in the environment. A mechanism of chemisorption and
      electron transfer from the molecular adsorbate to a redox-active transition metal
      or other receptor is shown through experiment, and supported by molecular orbital
      calculations, to result in PFR formation. Both oxygen-centered and carbon
      centered PFRs are possible that can significantly affect their environmental and
      biological reactivity.

PMID- 25598748
TI  - Opportunities for Operations Research in Medical Decision Making.

PMID- 25598749
TI  - DETERMINATION OF OXALATE ION DOPANT LEVEL IN POLYPYRROLE USING FT-IR.
AB  - A pellet method using standard addition and FT-IR was used to estimate oxalate
      ion doping levels in electrosynthesized polypyrrole. The method is useful for
      materials where removal of analyte from an insoluble material is problematic.
      Here, electrosynthesized oxalate doped polypyrrole is dispersed in potassium
      bromide. Spikes of sodium oxalate are added and the mixtures pressed into
      pellets. The oxalate carbonyl absorption peak is then used to quantify the amount
      of oxalate present in the polypyrrole. The mass fraction of oxalate dopant in
      polypyrrole was determined to be 0.4 +/- 0.1 % and coincides with the original
      synthesis solution composition.

PMID- 25598750
TI  - Rethinking Developmental Science.
AB  - The articles in this issue are all based on the invited addresses given by the
      authors at the 2013 biennial meeting of the Society for the Study of Human
      Development. All of the authors address the unfolding paradigm shift in
      developmental sciences, from reductionism to relational developmental system
      theories. This theoretical stance involves the recognition of Individual <->
      context transactions, with multiple co-acting partners existing in dynamic
      relationships across the lifespan and life course. The articles address not only
      theoretical issues, but also methodological advances and their applications.
      While acknowledging the importance of new data collection and analytical
      techniques that permit the testing of more complex theoretical models, the
      articles demonstrate that well-designed questions from this theoretical
      perspective can also yield novel findings which are highly relevant to current
      real-world problems and social policy issues.

PMID- 25598751
TI  - Varying degrees of ventricular unloading in the heterotopic rat heart transplant
      model demonstrated by magnetic resonance imaging.
AB  - OBJECTIVE: Left ventricular assist device placement is an increasingly common
      treatment for cardiac failure, resulting in cardiac unloading and potentially
      reversing the remodelling changes seen in heart failure. A popular animal model
      for human ventricular unloading is the rodent heterotopic non-working heart
      transplant; the volume loading status of this preparation is important to
      interpreting the resulting reverse remodelling yet has not been previously
      investigated. This study was designed to assess the variability of left
      ventricular volume loading in the rodent transplant model. METHODS: Heterotopic
      abdominal heart transplant was performed on syngeneic rats; high resolution cine
      magnetic resonance imaging was subsequently performed on the heterotopic
      transplanted hearts in anesthetised rats, after variable post-transplant recovery
      times, in order to assess ventricular loading status. RESULTS: Highly variable
      left ventricular volume loading status was demonstrated, with some hearts
      exhibiting considerable ventricular filling and ejection. CONCLUSIONS: These
      observations call into question the assumption that studies using this model are
      consistently examining fully unloaded ventricles, and indicate the desirability
      of in vivo imaging of such hearts to quantify the degree of ventricular loading.

PMID- 25598753
TI  - Serum glucose and malondialdehyde levels in alloxan induced diabetic rats
      supplemented with methanolic extract of tacazzea apiculata.
AB  - Tacazzea apiculata is used by traditional medical practitioners for the treatment
      of wide range of diseases. The current work investigated the hypoglycemic and
      antioxidant properties of Tacazzea apiculata Oliv. on alloxan induced diabetes
      mellitus. Five groups (n=10) of rats were fed on commercial diet. The rats were
      divided into Group 1 (NUT) as non-diabetic and untreated, group 2 (NDT) as non
      diabetic and treated, group 3 (DT) diabetic and treated. Group 4 (DUT) as
      diabetic and untreated. Group five (CP) were diabetic treated with
      Chlorpropamide, a drug used in the management of diabetic mellitus, with no known
      antioxidant property. Diabetic induction was done by intra-peritoneal injection
      of 100 mg/kg b. wt with alloxan. Fasting blood glucose was estimated seven days
      after induction to determine the severity of glucose elevation among the induced
      groups. Methanolic extract of T. apiculata leaf was administered to alloxan
      induced diabetic and non-diabetic control rats at 100mg/kg body weight for four
      weeks and blood glucose estimated on weekly basis. Malondialdehyde level was also
      estimated in the sera of the rats. Blood glucose level was monitored for
      additional 2 weeks post treatment. The results indicated that the extracts
      possess significant hypoglycemic effect on the diabetic rats (DT) having the mean
      glucose of (95.2 +/- 9.12 mg/dl) compared to the diabetic untreated control group
      (DUT) with a mean glucose of (238.91 +/- 4.42 mg/dl, p<0.05). The effect was
      sustained even on withdrawal of the extracts for two weeks. This was accompanied
      by a progressive increase in weight among all treated diabetic rats and non
      diabetic treated (DT and NDT) compared with diabetic untreated control rat (DUT)
      (p<0.05). A raised level in malondialdehyde was also observed among the diabetic
      rat prior to treatment and significantly decreased after the treatment. In
      conclusion the research demonstrated the hypoglycaemic and antioxidant potential
      of methanolic leaf extract of T. apiculata in alloxan induced rats. 

PMID- 25598752
TI  - Reduction of Serum ADAM17 Level Accompanied with Decreased Cytokines after
      Abatacept Therapy in Patients with Rheumatoid Arthritis.
AB  - A disintegrin and metalloprotease 17 (ADAM17) appears to be recognized as an
      important player in tissue destruction and also exacerbation of inflammation
      related with increased activities of angiogenesis in several pathological
      conditions. To examine the modulation of serum levels of ADAM17 and inflammatory
      cytokines in patients with rheumatoid arthritis (RA) in response to therapy of
      abatacept (ABT). Twenty four patients with RA were enrolled in our study. Serum
      was collected immediately prior to (baseline) and 24 weeks after starting ABT
      therapy. Serum levels of ADAM17 and cytokines/chemokine were quantified using
      enzyme-linked immunosorbent assay. ADAM17 level was markedly higher in RA
      patients than in healthy individuals. Positive correlation was observed between
      the baseline ADAM17 and CX3CL1 at baseline. There was a significant overall
      reduction of RA disease activity (Disease Activity Score 28) from 4.73 to 2.79
      after 24 weeks after the ABT therapy. Furthermore, there was a significant
      reduction in serum level of ADAM17 in RA patients, and the patients achieved
      clinical responses, and also clinical remission had a significant decrease in
      ADAM17 level and also levels of tumor necrosis factor alpha, IL-6 and CX3CL1
      after 24 weeks of ABT therapy. Our results suggest that the suppression of ADAM17
      secretion and function seems to be a crucial therapeutic target in the treatment
      of ABT in patients with RA. 

PMID- 25598754
TI  - Factors associated with postoperative pain in endodontic therapy.
AB  - OBJECTIVE: To assess postoperative pain in endodontic therapy and its association
      with clinical factors such as gender, age, tooth type, pulpal diagnosis, and
      preoperative pain, length of obturation and sealer extrusion. STUDY DESIGN: Cross
      Sectional study. PLACE AND DURATION OF STUDY: Dental section of the Aga khan
      university hospital, Karachi, Pakistan from January to December 2009.
      METHODOLOGY: One hundred and forty patients (140) requiring endodontic therapy
      for molar and premolar teeth were included in this study. Local Anesthesia (2%
      Lidocain with 1:80,000 Epinephrine) was administered. The tooth was isolated with
      rubber dam. Access cavity was prepared with the help of round carbide No. 2 bur.
      Canal preparation was completed using crown-down technique. Access was sealed
      with sterile dry cotton pallet and restored temporarily with double layer of
      Glass ionomer cement and Cavit. After one week patients were recalled and access
      was re-opened, obturation was done using cold lateral condensation technique.
      Ca(OH)(2) based sealer was used. Postoperative radiographs were taken. Patients
      were recalled after 24 hours and postobturation pain was recorded using Visual
      analogue scale (VAS).Data was obtained on a structured Performa. chi(2) test was
      used for statistical analysis. RESULTS: Pain was present in 42.9% of patients.
      Females more frequently experienced pain (65%) than males (35%). Preoperative
      pain was found to be significantly associated with postoperative pain (p value <
      0.001). Obturation length was not found to be significantly associated with
      postoperative pain (p value 1.0). Sealer extrusion was not found to be
      significantly associated with postoperative (P value 0.547).

PMID- 25598755
TI  - Comparison between Single Dose Azithromycin and Six Doses, 3 Day Norfloxacin for
      Treatment of Cholera in Adult.
AB  - AIM: To evaluate the efficacy of single dose Azithromycin (1 gram) in treatment
      of cholera in adults. A randomized, controlled clinical trial on 120 adults with
      acute watery diarrhoea and moderate to severe dehydration compared the efficacy
      of azithromycin (1 gram) single dose and Norfloxacin (400 mg) twice daily for
      three days in treating cholera. Data were analysed for 64 patients who were stool
      culture positive for Vibrio cholerae. In conjunction with rehydration therapy, 32
      patients received Azithromycin and 32 patients received Norfloxacin. Patients in
      the two treatment groups had comparable clinical characteristics on admission.
      CONCLUSIONS: Result shows Azithromycin and Norfloxacin has got almost similar
      efficacy in reducing stool output, duration of diarrhoea and fluid requirement in
      cholera positive cases.

PMID- 25598756
TI  - Relationship between Glycosylated Hemoglobin, Serum Nitric Oxide and Mean
      Arterial Blood Pressure.
AB  - BACKGROUND: Hypertension is about twice as frequent in individuals with diabetes
      as in those without diabetes. Formation of glycosylated conjugates like HbA1c is
      implicated to have many effects on the vascular endothelium which leads to the
      development of hypertension in diabetes. Nitric oxide (NO)-dependent
      vasodilatation has been shown to be an important factor in the maintenance and
      regulation of peripheral vascular tone. Studies correlating these parameters give
      conflicting results. Hence the present study was designed to correlate HbA1c,
      Serum NO & mean arterial blood pressure. AIMS: To study the relationship between
      glycosylated hemoglobin, serum nitric oxide & mean arterial blood pressure.
      SETTINGS AND DESIGN: It is a case control study with 28 type 2 diabetic
      hypertensives, 32 type 2 diabetic normotensives and 51 controls (non diabetic
      normotensives). MATERIALS & METHODS: The study subjects included 28 type 2
      diabetic hypertensives, 32 type 2 diabetic normotensives and 51 controls (non
      diabetic normotensives) [ADA 2010 and JNC7]. FBS, PPBS, PCV, Hb, HbA1c & serum NO
      estimation and BP recording was done in all the study subjects. Normalised mean
      arterial blood pressure (MAPn) and calculated glycosylated hemoglobin (cHbA1c)
      were calculated from mean arterial BP (MAP) and HbA1c respectively. STATISTICAL
      ANALYSIS: was done using R commander software. The difference in the distribution
      of cHbA1c, MAPn & NO levels between all 3 groups was measured using ANOVA and
      Kruskal-Wallis test. Correlation between the parameters was measured by
      Correlation coefficient and logistic regression (Spearman linear regression)
      analysis (univariate and multivariate). RESULTS: There was a significant
      difference in the distribution of cHbA1c, MAPn & NO levels (p<0.001) between all
      3 groups, whether measured by ANOVA or Kruskal-Wallis test. On univariate
      analysis, there was a positive correlation between cHbA1c & MAPn (rho= +0.26), a
      negative correlation between NO & MAPn (rho = -0.54) and cHbA1c & NO (rho= -0.66)
      .On multivariate analysis, not only NO, but contrary to univariate analysis,
      cHbA1c also showed a negative association with MAPn. CONCLUSION: As the severity
      of diabetes increases, there is increase in BP, which is mainly due to the marked
      decrease in NO level which masks the negative correlation between HbA1c on MAPn.

PMID- 25598757
TI  - Bu-shen-he-mai-fang (HMF) Decoction Inhibits Atherosclerosis by Improving
      Antioxidant and Anti-Inflammatory Activities in ApoE-deficient Mice.
AB  - OBJECTIVE: To observe the effects of Bu-shen- he- mai- fang (HMF) on experimental
      atherosclerosis in ApoE-deficient mice. MATERIALS AN METHODS: Thirty male ApoE
      deficient mice were randomly divided into 3 groups (10 mice per group) as
      follows: one group received the standard high- cholesterol diet (high-
      cholesterol group, HC); Another group received high- cholesterol diet
      supplemented with HMF decoction 1.37 g/kg/day; the third group received a high-
      cholesterol diet, supplemented with atrovastatin 5 mg/kg/day for 8 weeks. The
      extent of atherosclerosis, the expression of LOX-1 protein and macrophage
      infiltration were evaluated by H&E, oil red O staining, and immunohistochemical
      staining. SOD was also measured by a spectrophotometer. RESULTS: The degree of
      atherosclerosis was significantly lower in HMF group and atrovastatin group than
      that in high-cholesterol group. The expression of LOX-1 protein and macrophage
      filtration were significantly lower in HMF group and atrovastatin group than that
      in high-cholesterol group. Also, the SOD was higher in HMF group and atrovastatin
      group than that in high-cholesterol group. CONCLUSION: The results suggested that
      HMF significantly inhibited early atherosclerotic lesions by inhibiting
      inflammatory response and decreasing the generation of ROS.

PMID- 25598758
TI  - Role of Brushing and Occlusal Forces in Non-Carious Cervical Lesions (NCCL).
AB  - OBJECTIVE: To assess the association of occlusal forces and brushing with non
      carious cervical lesions (NCCL). METHODOLOGY: It was a Cross-sectional study. The
      study was conducted in Dental clinics, Department of Surgery, The Aga Khan
      University Hospital Karachi. The study duration was from 1(st) January 2009 to
      28(th) Feb 2009. Ninety patients visiting dental clinic were examined clinically.
      Presence of Non- carious cervical lesions, broken restorations, fractured cusps,
      presence of occlusal facets, brushing habits, Para functional habits were
      assessed. All the relevant information and clinical examination were collected on
      a structured Performa and was analyzed using SPSS version 14.0. . Chi square
      chi(2) test was applied to assess association among different categorical
      variables. RESULT: Twenty three (26%) females and 67 (74%) males were included in
      the study. Thirty five of them (38.9%) were found to have Non-carious cervical
      lesions. Presence of NCCL has no association with gender (P value 0.458). A
      significant association was found between NCCL and teeth sensitivity (P value
      0.002).The association between use of hard tooth brush and Non-carious cervical
      lesions was found significant (P value <0.001). However the association among Non
      carious cervical lesions and fractured cups, broken restoration, teeth grinding,
      jaw clenching, pan chalia chewing and frequency of teeth brushing were
      insignificant. CONCLUSION: Hard tooth brushing and teeth sensitivity have
      significant association with Non-carious cervical lesions. The role of occlusal
      wear in the formation of NCCL is not significant.

PMID- 25598759
TI  - Low seroprevalence of Toxocara infection in schizophrenic inpatients in durango,
      Mexico: a case control study.
AB  - Psychiatric patients have a higher seroprevalence of toxocariasis than general
      population. However, there is poor knowledge about any specific psychiatric
      diagnosis associated with toxocariasis. The aim of the study was to determine
      whether seropositivity to Toxocara was associated with schizophrenia. Through an
      age and gender-matched case-control seroprevalence study in Durango City, Mexico,
      50 schizophrenic inpatients in a public psychiatric hospital and 100 control
      subjects of the general population were compared for the presence of anti
      Toxocara IgG antibodies. One of the 50 (2%) schizophrenic inpatients, and 3 (3%)
      of the 100 controls were positive for anti-Toxocara IgG antibodies. No
      statistically significant difference in Toxocara seroprevalence among cases and
      controls was found (P=0.59). The Toxocara positive schizophrenic patient suffered
      from paranoid schizophrenia (F20.0) and had a number of putative risk factors for
      Toxocara exposure including contact with cats, dogs and other animals, worked in
      agriculture, and consumed undercooked meat, unwashed fruits and vegetables, and
      untreated water. Results suggest that seroprevalence of Toxocara infection was
      low and not associated with schizophrenia in psychiatric inpatients in Durango,
      Mexico. However, further studies to elucidate the association of toxocariasis
      with schizophrenia are needed. 

PMID- 25598760
TI  - HPLC-DAD Analysis and In-Vitro Property of Polyphenols Extracts from (Solanum
      Aethiopium) Fruits on alpha -Amylase, alpha -Glucosidase and Angiotensin - 1-
      Converting Enzyme Activities.
AB  - AIM: Garden egg (Solanum aethiopium) is an edible fruits vegetable with 
      different species.This study investigated characterisation and the effect of the
      phenolics extracts from S. aethiopium species with enzymes linked with type -2
      diabetes (alpha-amylase and alpha-glucosidase) and hypertension [Angiotensin-1
      converting enzyme (ACE)]. METHODS: Fresh samples of the 5 species of the garden
      egg namely, [Solanum gilo (PW), Solanum torvum (TWS), Solanum kumba (PGR),
      Solanum incanum (GSB), and Solanum indicum (WSB)] were oven-dried at 50 degrees C
      and milled into flour. The aqueous extracts were prepared (1:50 w/v). The
      phenolic contents (total phenol and total flavonoid), vitamin C and 1,1-diphenyl
      2-picrylhydrazyl (DPPH), the antioxidant activities of the extracts were
      evaluated. The ability of the extracts to inhibit diabetes enzymes in rat
      pancreas as well as the inhibition of angiotensin-1-converting (ACE) enzyme in
      lungs homogenates in vitro were investigated. Furthermore, the fruits polyphenols
      were identified and quantified using HPLC-DAD. RESULTS: The phenolic contents
      ranged from 2.70-3.76 mgGAE/g, while there were no significant (P>0.05)
      differences in their flavonoid content and ability to reduce Fe(3+) to Fe(2+).
      The vitamin C contents of the species ranged from 4.01-6.52 mg/ml. The extracts
      scavenged DPPH in a dose dependent manner with the IC50 values ranging from 3.23
      4.20 mg/ml. Furthermore, the extracts showed strong inhibition of alpha
      glucosidase, mild inhibition of alpha-amylase and strong inhibition of ACE
      activities. CONCLUSION: This study showed that the inhibition of the key enzymes
      relevant to type-2 diabetes and hypertension could be part of the mechanisms by
      which garden egg manage/prevent the degenerative conditions.

PMID- 25598763
TI  - Trajectory Synthesis for Fisher Information Maximization.
AB  - Estimation of model parameters in a dynamic system can be significantly improved
      with the choice of experimental trajectory. For general nonlinear dynamic
      systems, finding globally "best" trajectories is typically not feasible; however,
      given an initial estimate of the model parameters and an initial trajectory, we
      present a continuous-time optimization method that produces a locally optimal
      trajectory for parameter estimation in the presence of measurement noise. The
      optimization algorithm is formulated to find system trajectories that improve a
      norm on the Fisher information matrix (FIM). A double-pendulum cart apparatus is
      used to numerically and experimentally validate this technique. In simulation,
      the optimized trajectory increases the minimum eigenvalue of the FIM by three
      orders of magnitude, compared with the initial trajectory. Experimental results
      show that this optimized trajectory translates to an order-of-magnitude
      improvement in the parameter estimate error in practice.

PMID- 25598761
TI  - Sloughing esophagitis: a not so common entity.
AB  - BACKGROUND: Sloughing esophagitis, also known as esophagitis dissecans
      superficialis, is a very rare and underdiagnosed entity with unknown incidence
      rate. It can be associated with bullous dermatoses and medications such as
      central nervous system depressants and those causing esophageal injury. CASE
      REPORT: A 55-years-old woman was recovering from renal failure due to
      rhabdomyolysis when she developed dysphagia and odynophagia.
      Esophagogastroduodenoscopy with biopsy was performed for suspected bullous
      pemphigus and confirmed sloughing esophagitis. She improved with intravenous
      steroids. CONCLUSIONS: Sloughing Esophagitis should enter our differential
      diagnosis more frequently. It is mostly a benign, self-limiting process but when
      associated with bullous dermatoses will require steroid treatment.

PMID- 25598762
TI  - Unique presentations of invasive lobular breast cancer: a case series.
AB  - INTRODUCTION: Breast carcinoma is the most common malignancy in women. Unlike
      IDC, which typically metastasizes to the lung, liver or bone, ILC has been found
      to metastasize to GI tract, peritoneum and retroperitoneum. Nonspecific
      symptomology may be considered secondary to other diseases and this can delay the
      definite diagnosis and treatment of metastatic disease. Knowledge of the pattern
      of disease spread is essential for accurate diagnosis and early initiation of
      systemic treatment, thus avoiding unnecessary interventions. We are reporting
      three unique cases of metastatic ILC presenting with wide range of symptoms. CASE
      PRESENTATIONS: Case A: 69-year-old female presented with recurrent jaundice. Case
      B: 77-year-old female with the past medical history of right breast ILC seven
      years ago status post right radical mastectomy with chemotherapy, presented with
      anemia. Case C: 56-year-old female presented with bright red blood per rectum.
      CONCLUSION: A high level of suspicion is needed for metastatic breast cancer in
      patients with history of ILC, regardless of disease free interval. Since it
      frequently metastasizes to unusual sites and presents with a wide spectrum of
      symptoms.

PMID- 25598766
TI  - Chemometric evaluation of Saccharomyces cerevisiae metabolic profiles using LC
      MS.
AB  - A new liquid chromatography mass spectrometry (LC-MS) metabolomics strategy
      coupled to chemometric evaluation, including variable and biomarker selection,
      has been assessed as a tool to discriminate between control and stressed
      Saccharomyces cerevisiae yeast samples. Metabolic changes occurring during yeast
      culture at different temperatures (30 and 42  degrees C) were analysed and the
      complex data generated in profiling experiments were evaluated by different
      chemometric multivariate approaches. Multivariate curve resolution alternating
      least squares (MCR-ALS) was applied to full spectral scan LC-MS preprocessed data
      multisets arranged in augmented column-wise data matrices. The results showed
      that sectioning the MS-chromatograms in different windows and analysing them by
      MCR-ALS enabled the proper resolution of very complex coeluted chromatographic
      peaks. The investigation of possible relationships between MCR-ALS resolved
      chromatographic peak areas and culture temperature was then investigated by
      partial least squares discriminant analysis (PLS-DA). Selection of most relevant
      resolved chromatographic peaks associated to yeast culture temperature changes
      was achieved according to PLS-DA-Variable Importance in Projection scores. A
      metabolite identification workflow was developed utilizing MCR-ALS resolved pure
      MS spectra and high-resolution accurate mass measurements to confirm assigned
      structures based on entries in metabolite databases. A total of 65 metabolites
      were identified. A preliminary interpretation of these results indicates that the
      strategy described in this study can be proposed as a general tool to facilitate
      biomarker identification and modelling in similar untargeted metabolomic studies.

PMID- 25598765
TI  - Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's
      disease and healthy individuals.
AB  - This study employs spectroscopy-based metabolic profiling of fecal extracts from
      healthy subjects and patients with active or inactive ulcerative colitis (UC) and
      Crohn's disease (CD) to substantiate the potential use of spectroscopy as a non
      invasive diagnostic tool and to characterize the fecal metabolome in inflammatory
      bowel disease (IBD). Stool samples from 113 individuals (UC 48, CD 44, controls
      21) were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy (Bruker 600
      MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with principal
      component analysis and orthogonal-projection to latent structure-discriminant
      analysis using SIMCA-P + 12 and MATLAB. Significant differences were found in the
      metabolic profiles making it possible to differentiate between active IBD and
      controls and between UC and CD. The metabolites holding differential power
      primarily belonged to a range of amino acids, microbiota-related short chain
      fatty acids, and lactate suggestive of an inflammation-driven malabsorption and
      dysbiosis of the normal bacterial ecology. However, removal of patients with
      intestinal surgery and anti-TNF-alpha antibody treatment eliminated the
      discriminative power regarding UC versus CD. This study consequently demonstrates
      that 1H NMR spectroscopy of fecal extracts is a potential non-invasive diagnostic
      tool and able to characterize the inflammation-driven changes in the metabolic
      profiles related to malabsorption and dysbiosis. Intestinal surgery and
      medication are to be accounted for in future studies, as it seems to be factors
      of importance in the discriminative process.

PMID- 25598764
TI  - Molecular phenotyping of a UK population: defining the human serum metabolome.
AB  - Phenotyping of 1,200 'healthy' adults from the UK has been performed through the
      investigation of diverse classes of hydrophilic and lipophilic metabolites
      present in serum by applying a series of chromatography-mass spectrometry
      platforms. These data were made robust to instrumental drift by numerical
      correction; this was prerequisite to allow detection of subtle metabolic
      differences. The variation in observed metabolite relative concentrations between
      the 1,200 subjects ranged from less than 5 % to more than 200 %. Variations in
      metabolites could be related to differences in gender, age, BMI, blood pressure,
      and smoking. Investigations suggest that a sample size of 600 subjects is both
      necessary and sufficient for robust analysis of these data. Overall, this is a
      large scale and non-targeted chromatographic MS-based metabolomics study, using
      samples from over 1,000 individuals, to provide a comprehensive measurement of
      their serum metabolomes. This work provides an important baseline or reference
      dataset for understanding the 'normal' relative concentrations and variation in
      the human serum metabolome. These may be related to our increasing knowledge of
      the human metabolic network map. Information on the Husermet study is available
      at http://www.husermet.org/. Importantly, all of the data are made freely
      available at MetaboLights (http://www.ebi.ac.uk/metabolights/).

PMID- 25598767
TI  - Jumping on the Train of Personalized Medicine: A Primer for Non-Geneticist
      Clinicians: Part 2. Fundamental Concepts in Genetic Epidemiology.
AB  - With the decrease in sequencing costs, personalized genome sequencing will
      eventually become common in medical practice. We therefore write this series of
      three reviews to help non-geneticist clinicians to jump into the fast-moving
      field of personalized medicine. In the first article of this series, we reviewed
      the fundamental concepts in molecular genetics. In this second article, we cover
      the key concepts and methods in genetic epidemiology including the classification
      of genetic disorders, study designs and their implementation, genetic marker
      selection, genotyping and sequencing technologies, gene identification
      strategies, data analyses and data interpretation. This review will help the
      reader critically appraise a genetic association study. In the next article, we
      will discuss the clinical applications of genetic epidemiology in the
      personalized medicine area.

PMID- 25598769
TI  - Collecting Information for Rating Global Assessment of Functioning (GAF): Sources
      of Information and Methods for Information Collection.
AB  - INTRODUCTION: Global Assessment of Functioning (GAF) is an assessment instrument
      that is known worldwide. It is widely used for rating the severity of illness.
      Results from evaluations in psychiatry should characterize the patients. Rating
      of GAF is based on collected information. The aim of the study is to identify the
      factors involved in collecting information that is relevant for rating GAF, and
      gaps in knowledge where it is likely that further development would play a role
      for improved scoring. METHODS: A literature search was conducted with a
      combination of thorough hand search and search in the bibliographic databases
      PubMed, PsycINFO, Google Scholar, and Campbell Collaboration Library of
      Systematic Reviews. RESULTS: Collection of information for rating GAF depends on
      two fundamental factors: the sources of information and the methods for
      information collection. Sources of information are patients, informants, health
      personnel, medical records, letters of referral and police records about violence
      and substance abuse. Methods for information collection include the many
      different types of interview - unstructured, semi-structured, structured,
      interviews for Axis I and II disorders, semistructured interviews for rating GAF,
      and interviews of informants - as well as instruments for rating symptoms and
      functioning, and observation. The different sources of information, and methods
      for collection, frequently result in inconsistencies in the information
      collected. The variation in collected information, and lack of a generally
      accepted algorithm for combining collected information, is likely to be important
      for rated GAF values, but there is a fundamental lack of knowledge about the
      degree of importance. CONCLUSIONS: Research to improve GAF has not reached a high
      level. Rated GAF values are likely to be influenced by both the sources of
      information used and the methods employed for information collection, but the
      lack of research-based information about these influences is fundamental. Further
      development of GAF is feasible and proposals for this are presented.

PMID- 25598768
TI  - Jumping on the Train of Personalized Medicine: A Primer for Non- Geneticist
      Clinicians: Part 3. Clinical Applications in the Personalized Medicine Area.
AB  - The rapid decline of sequencing costs brings hope that personal genome sequencing
      will become a common feature of medical practice. This series of three reviews
      aim to help non-geneticist clinicians to jump into the fast-moving field of
      personalized genetic medicine. In the first two articles, we covered the
      fundamental concepts of molecular genetics and the methodologies used in genetic
      epidemiology. In this third article, we discuss the evolution of personalized
      medicine and illustrate the most recent success in the fields of Mendelian and
      complex human diseases. We also address the challenges that currently limit the
      use of personalized medicine to its full potential.

PMID- 25598772
TI  - Multifaceted intervention including motivational interviewing to support
      medication adherence after stroke/transient ischemic attack: a randomized trial.
AB  - BACKGROUND AND PURPOSE: Adherence to medication is often suboptimal after stroke
      and transient ischemic attack (TIA), which increases the risk of recurrent stroke
      and death. Complex interventions and motivational interviewing (MI) have been
      proven effective in other areas of medicine. The objective of this study was to
      investigate the effectiveness of a multifaceted intervention including MI in
      improving medication adherence for secondary stroke prevention. METHODS: In this
      randomized controlled trial, TIA and stroke patients receiving a pharmacist
      intervention in a hospital setting were compared with patients receiving usual
      care. The intervention consisted of a focused medication review, an MI-approached
      consultation and 3 follow-up telephone calls and lasted for 6 months. The primary
      outcome was a composite medication possession ratio (MPR) for antiplatelets,
      anticoagulants and statins in the year after hospitalization, assessed by
      analyzing pharmacy records and reported as both a continuous rate and a binary
      outcome. Secondary outcomes included composite MPRs at 3, 6 and 9 months as well
      as adherence and persistence to specific thrombopreventive medications at 12
      months. Clinical outcomes included a combined end point of cardiovascular death,
      stroke or acute myocardial infarction. Patient satisfaction with the service was
      assessed for the intervention patients. RESULTS: The analyses included 102
      intervention patients and 101 controls. At 12 months, the median MPRs (IQR) were
      0.95 (0.77-1) in the intervention group and 0.91 (0.83-0.99) in the control
      group, and 28 and 21% of the patients, respectively, were nonadherent (MPR <0.80;
      risk difference: 7%; 95% CI: -5 to 19%). In both groups, the median MPR decreased
      over time. From 3 to 12 months, the MPR fell by 5% (p < 0.05) in the intervention
      group and by 9% (p < 0.05) in the control group, but between the groups,
      comparisons showed no statistically significant difference. No significant
      differences were found for adherence and persistence to specific
      thrombopreventive agents or for the clinical outcome. The intervention patients
      were satisfied with the service; about half of them reported increased knowledge
      about medication, and one third reported increased confidence with medication
      use. Pharmacists identified drug-related problems in one third of the patients.
      CONCLUSIONS: A multifaceted pharmacist intervention including MI did not improve
      adherence or persistence to secondary stroke prevention therapy and had no impact
      on clinical outcomes. However, due to the high adherence rates, only little room
      for improvement existed. Future studies should focus on patients at high risk of
      nonadherence and include outcomes more sensitive to the impact of behavioral
      interventions.

PMID- 25598770
TI  - Physical activity and cognitive functioning in the oldest old: Within- and
      between-person cognitive activity and psychosocial mediators.
AB  - OBJECTIVE: The current study examines the role of social contact intensity,
      cognitive activity, and depressive symptoms as within- and between-person
      mediators for the relationships between physical activity and cognitive
      functioning. METHOD: All three types of mediators were considered simultaneously
      using multilevel structural equations modeling with longitudinal data. The sample
      consisted of 470 adults ranging from 79.37 to 97.92 years of age (M = 83.4; SD =
      3.2) at the first occasion. RESULTS: Between-person differences in cognitive
      activity mediated the relationship between physical activity and cognitive
      functioning, such that individuals who participated in more physical activities,
      on average, engaged in more cognitive activities and, in turn, showed better
      cognitive functioning. Mediation of between-person associations between physical
      activity and memory through social contact intensity was also significant. At the
      within-person level, only cognitive activity mediated the relationship between
      physical activity and change in cognition; however, the indirect effect was
      small. Depressive symptomatology was not found to significantly mediate within-
      or between-person effects on cognitive change. DISCUSSION: Our findings highlight
      the implications of physical activity participation for the prevention of
      cognitive decline and the importance of meditational processes at the between
      person level. Physical activity can provide older adults with an avenue to make
      new friendships and engage in more cognitive activities which, in turn,
      attenuates cognitive decline.

PMID- 25598771
TI  - Cerebral microbleeds are associated with worse cognitive function in the
      nondemented elderly with small vessel disease.
AB  - BACKGROUND: Cerebral small vessel disease (SVD) is a leading cause of cognitive
      decline in the elderly. Cerebral microbleeds (CMBs) have emerged as an important
      manifestation of cerebral SVD, in addition to lacunar infarcts and white matter
      lesions (WMLs). We investigated whether the presence and location of CMBs in
      elderly subjects were associated with cognitive function, independent of lacunar
      infarcts and WMLs. METHODS: One hundred and forty-eight nondemented elderly with
      SVD, defined as the presence of lacunar infarcts and/or WMLs on magnetic
      resonance imaging (MRI), were studied. Executive function and global cognition
      were assessed by the Frontal Assessment Battery (FAB) and Mini-Mental State
      Examination (MMSE), respectively. The differences in the scores for the FAB and
      MMSE between CMB-positive and CMB-negative subjects were calculated after
      adjusting for possible confounders. RESULTS: The mean age of the subjects was
      72.4 +/- 8.6 years. CMBs were detected in 48 subjects (32%), with a mean number
      of CMBs per subject of 1.6 (range 0-31). Among CMB-positive subjects, 42 (87.5%)
      had CMBs in deep or infratentorial regions with or without lobar CMBs, and 6
      (12.5%) had CMBs in strictly lobar regions. The presence of CMBs was
      significantly associated with FAB and MMSE scores after adjustment for age, years
      of education, brain volume and the presence of lacunar infarcts (for the FAB) or
      severe WMLs (for the MMSE). The presence of CMBs in the basal ganglia, in the
      thalamus or in the lobar regions was associated with FAB scores, while that in
      the lobar regions was associated with MMSE scores. However, there was no
      association between CMBs in the infratentorial regions and cognitive parameters.
      CONCLUSIONS: In nondemented elderly with SVD on MRI, the presence of CMBs was
      independently associated with worse executive and global cognitive functions.
      CMBs seemed to reflect hypertensive microangiopathy in this population, and CMBs
      in specific areas may play an important role in cognitive function.

PMID- 25598774
TI  - New perspectives for investigating respiratory failure induced by cervical spinal
      cord injury.

PMID- 25598775
TI  - Two faces of Schwann cell dedifferentiation in peripheral neurodegenerative
      diseases: pro-demyelinating and axon-preservative functions.

PMID- 25598773
TI  - Extracellular matrix components in peripheral nerve repair: how to affect neural
      cellular response and nerve regeneration?
AB  - Peripheral nerve injury is a serious problem affecting significantly patients'
      life. Autografts are the "gold standard" used to repair the injury gap, however,
      only 50% of patients fully recover from the trauma. Artificial conduits are a
      valid alternative to repairing peripheral nerve. They aim at confining the nerve
      environment throughout the regeneration process, and providing guidance to axon
      outgrowth. Biocompatible materials have been carefully designed to reduce
      inflammation and scar tissue formation, but modifications of the inner lumen are
      still required in order to optimise the scaffolds. Biomicking the native neural
      tissue with extracellular matrix fillers or coatings showed great promises in
      repairing longer gaps and extending cell survival. In addition, extracellular
      matrix molecules provide a platform to further bind growth factors that can be
      released in the system over time. Alternatively, conduit fillers can be used for
      cell transplantation at the injury site, reducing the lag time required for
      endogenous Schwann cells to proliferate and take part in the regeneration
      process. This review provides an overview on the importance of extracellular
      matrix molecules in peripheral nerve repair. 

PMID- 25598776
TI  - Bacteriophages and development of nanomaterials for neural regeneration.

PMID- 25598777
TI  - Evaluating nerve guidance conduits for peripheral nerve injuries: a novel
      normalization method.

PMID- 25598778
TI  - Dorsal root ganglion-derived Schwann cells combined with poly(lactic-co-glycolic
      acid)/chitosan conduits for the repair of sciatic nerve defects in rats.
AB  - Schwann cells, nerve regeneration promoters in peripheral nerve tissue
      engineering, can be used to repair both the peripheral and central nervous
      systems. However, isolation and purification of Schwann cells are complicated by
      contamination with fibroblasts. Current reported measures are mainly limited by
      either high cost or complicated procedures with low cell yields or purity. In
      this study, we collected dorsal root ganglia from neonatal rats from which we
      obtained highly purified Schwann cells using serum-free melanocyte culture
      medium. The purity of Schwann cells (> 95%) using our method was higher than that
      using standard medium containing fetal bovine serum. The obtained Schwann cells
      were implanted into poly(lactic-co-glycolic acid)/chitosan conduits to repair 10
      mm sciatic nerve defects in rats. Results showed that axonal diameter and area
      were significantly increased and motor functions were obviously improved in the
      rat sciatic nerve tissue. Experimental findings suggest that serum-free
      melanocyte culture medium is conducive to purify Schwann cells and poly(lactic-co
      glycolic acid)/chitosan nerve conduits combined with Schwann cells contribute to
      restore sciatic nerve defects. 

PMID- 25598779
TI  - Differentiation of mesenchymal stem cells into neuronal cells on fetal bovine
      acellular dermal matrix as a tissue engineered nerve scaffold.
AB  - The purpose of this study was to assess fetal bovine acellular dermal matrix as a
      scaffold for supporting the differentiation of bone marrow mesenchymal stem cells
      into neural cells following induction with neural differentiation medium. We
      performed long-term, continuous observation of cell morphology, growth,
      differentiation, and neuronal development using several microscopy techniques in
      conjunction with immunohistochemistry. We examined specific neuronal proteins and
      Nissl bodies involved in the differentiation process in order to determine the
      neuronal differentiation of bone marrow mesenchymal stem cells. The results show
      that bone marrow mesenchymal stem cells that differentiate on fetal bovine
      acellular dermal matrix display neuronal morphology with unipolar and
      bi/multipolar neurite elongations that express neuronal-specific proteins,
      including betaIII tubulin. The bone marrow mesenchymal stem cells grown on fetal
      bovine acellular dermal matrix and induced for long periods of time with neural
      differentiation medium differentiated into a multilayered neural network-like
      structure with long nerve fibers that was composed of several parallel
      microfibers and neuronal cells, forming a complete neural circuit with dendrite
      dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones
      with filopodia were observed using scanning electron microscopy. Paraffin
      sectioning showed differentiated bone marrow mesenchymal stem cells with the
      typical features of neuronal phenotype, such as a large, round nucleus and a
      cytoplasm full of Nissl bodies. The data suggest that the biological scaffold
      fetal bovine acellular dermal matrix is capable of supporting human bone marrow
      mesenchymal stem cell differentiation into functional neurons and the subsequent
      formation of tissue engineered nerve. 

PMID- 25598780
TI  - Restorative effect and mechanism of mecobalamin on sciatic nerve crush injury in
      mice.
AB  - Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt),
      is one of the most important mediators of nervous system function. In the clinic,
      it is often used to accelerate recovery of peripheral nerves, but its molecular
      mechanism remains unclear. In the present study, we performed sciatic nerve crush
      injury in mice, followed by daily intraperitoneal administration of mecobalamin
      (65 MUg/kg or 130 MUg/kg) or saline (negative control). Walking track analysis,
      histomorphological examination, and quantitative real-time PCR showed that
      mecobalamin significantly improved functional recovery of the sciatic nerve,
      thickened the myelin sheath in myelinated nerve fibers, and increased the cross
      sectional area of target muscle cells. Furthermore, mecobalamin upregulated mRNA
      expression of growth associated protein 43 in nerve tissue ipsilateral to the
      injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve
      growth factor and ciliary neurotrophic factor) in the L4-6 dorsal root ganglia.
      Our findings indicate that the molecular mechanism underlying the therapeutic
      effect of mecobalamin after sciatic nerve injury involves the upregulation of
      multiple neurotrophic factor genes. 

PMID- 25598781
TI  - Age-dependent loss of cholinergic neurons in learning and memory-related brain
      regions and impaired learning in SAMP8 mice with trigeminal nerve damage.
AB  - The tooth belongs to the trigeminal sensory pathway. Dental damage has been
      associated with impairments in the central nervous system that may be mediated by
      injury to the trigeminal nerve. In the present study, we investigated the effects
      of damage to the inferior alveolar nerve, an important peripheral nerve in the
      trigeminal sensory pathway, on learning and memory behaviors and structural
      changes in related brain regions, in a mouse model of Alzheimer's disease.
      Inferior alveolar nerve transection or sham surgery was performed in middle-aged
      (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8
      (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or
      11 months (middle-aged group 2), and the elderly group reached 11 months, step
      down passive avoidance and Y-maze tests of learning and memory were performed,
      and the cholinergic system was examined in the hippocampus (Nissl staining and
      acetylcholinesterase histochemistry) and basal forebrain (choline
      acetyltransferase immunohistochemistry). In the elderly group, animals that
      underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1
      and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer
      cholinergic neurons in the medial septal nucleus and vertical limb of the
      diagonal band, compared with sham-operated animals, as well as showing
      impairments in learning and memory. Conversely, no significant differences in
      histology or behavior were observed between middle-aged group 1 or group 2
      transected mice and age-matched sham-operated mice. The present findings suggest
      that trigeminal nerve damage in old age, but not middle age, can induce
      degeneration of the septal-hippocampal cholinergic system and loss of hippocampal
      pyramidal neurons, and ultimately impair learning ability. Our results highlight
      the importance of active treatment of trigeminal nerve damage in elderly patients
      and those with Alzheimer's disease, and indicate that tooth extraction should be
      avoided in these populations. 

PMID- 25598782
TI  - CD93 and GIPC expression and localization during central nervous system
      inflammation.
AB  - CD93 and GAIP-interacting protein, C termius (GIPC) have been shown to
      interactively alter phagocytic processes of immune cells. CD93 and GIPC
      expression and localization during central nervous system inflammation have not
      yet been reported. In this study, we established a rat model of brain
      inflammation by lipopolysaccharide injection to the lateral ventricle. In the
      brain of rats with inflammation, western blots showed increased CD93 expression
      that decreased over time. GIPC expression was unaltered. Immunohistochemistry
      demonstrated extensive distribution of CD93 expression mainly in cell membranes
      in the cerebral cortex. After lipopolysaccharide stimulation, CD93 expression
      increased and then reduced, with distinct staining in the cytoplasm and nucleus.
      Double immunofluorescence staining in cerebral cortex of normal rats showed that
      CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly
      expressed in microglial and neuronal cell membranes, while GIPC was expressed in
      both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model
      establishment, CD93-immunoreactive signal diminished in microglial membrane, with
      cytoplasmic translocation and aggregation detected. GIPC localization was
      unaltered in neurons and microglia. These results are the first to demonstrate
      CD93 participation in pathophysiological processes of central nervous system
      inflammation. 

PMID- 25598783
TI  - Propofol and remifentanil at moderate and high concentrations affect
      proliferation and differentiation of neural stem/progenitor cells.
AB  - Propofol and remifentanil alter intracellular Ca(2+) concentration ([Ca(2+)]i) in
      neural stem/progenitor cells by activating gamma-aminobutyric acid type A
      receptors and by reducing testosterone levels. However, whether this process
      affects neural stem/progenitor cell proliferation and differentiation remains
      unknown. In the present study, we applied propofol and remifentanil, alone or in
      combination, at low, moderate or high concentrations (1, 2-2.5 and 4-5 times the
      clinically effective blood drug concentration), to neural stem/progenitor cells
      from the hippocampi of newborn rat pups. Low concentrations of propofol,
      remifentanil or both had no noticeable effect on cell proliferation or
      differentiation; however, moderate and high concentrations of propofol and/or
      remifentanil markedly suppressed neural stem/progenitor cell proliferation and
      differentiation, and induced a decrease in [Ca(2+)]i during the initial stage of
      neural stem/progenitor cell differentiation. We therefore propose that propofol
      and remifentanil interfere with the proliferation and differentiation of neural
      stem/progenitor cells by altering [Ca(2+)]i. Our findings suggest that propofol
      and/or remifentanil should be used with caution in pediatric anesthesia. 

PMID- 25598784
TI  - Evaluation of spinal cord injury animal models.
AB  - Because there is no curative treatment for spinal cord injury, establishing an
      ideal animal model is important to identify injury mechanisms and develop
      therapies for individuals suffering from spinal cord injuries. In this article,
      we systematically review and analyze various kinds of animal models of spinal
      cord injury and assess their advantages and disadvantages for further studies. 

PMID- 25598785
TI  - Visualization analysis of research frontiers and trends in nerve regeneration and
      osseoperception in the repair of tooth loss.
AB  - This study analyzed 85 articles indexed by the Web of Science concerning nerve
      regeneration and osseoperception during tooth loss repair. Using the Web of
      Science database and Citespace III software, a document co-citation network map
      was drawn by document co-citation analysis and word frequency analysis methods.
      Combined with emergent node secondary literature retrieval, subject headings with
      apparent changing word frequency trends were retrieved so as to identify research
      frontiers and development trends. Research frontiers and hotspots for neuronal
      calcium sensor protein were quantitatively explored to forecast future research
      developments in nerve regeneration and osseoperception during repair of tooth
      loss. 

PMID- 25598786
TI  - Entecavir versus Lamivudine therapy for patients with chronic hepatitis B
      associated liver failure: a meta-analysis.
AB  - BACKGROUND: Nucleoside analogues are recommended as antiviral treatments for
      patients with hepatitis B virus (HBV)-associated liver failure. Clinical data
      comparing entecavir (ETV) and lamivudine (LAM) are inconsistent in this setting.
      OBJECTIVES: To compare the efficacy and safety of ETV and LAM in patients with
      chronic hepatitis B (CHB)-associated liver failure. PATIENTS AND METHODS: A
      literature search was performed on articles published until January 2014 on
      therapy with ETV and LAM for patients with CHB-associated liver failure. Risk
      ratio (RR) and mean difference (MD) were used to measure the effects. Survival
      rate was the primary efficacy measure, while total bilirubin (TBIL), prothrombin
      activity (PTA) changes and HBV DNA negative change rates were secondary efficacy
      measures. A quantitative meta-analysis was performed to compare the efficacy of
      the two drugs. Safety of ETV and LAM was observed. RESULTS: Four randomized
      controlled trials and nine retrospective cohort studies comprising a total of
      1549 patients were selected. Overall analysis revealed comparable survival rates
      between patients received ETV and those received LAM (4 weeks: RR = 1.03, 95%CI
      [0.89, 1.18], P = 0.73; 8 weeks: RR = 0.98, 95% CI [0.85, 1.14], P = 0.84; 12
      weeks: RR = 0.98, 95% CI [0.90, 1.08], P = 0.70; 24 weeks: RR = 1.02, 95% CI
      [0.94, 1.10], P = 0.66). After 24 weeks of treatment, patients treated with ETV
      had a significantly lower TBIL levels (MD = -37.34, 95% CI [-63.57, -11.11], P =
      0.005), higher PTA levels (MD = 11.10, 95% CI [2.47, 19.73], P = 0.01) and higher
      HBV DNA negative rates (RR = 2.76, 95% CI [1.69, 4.51], P < 0.0001) than those
      treated with LAM. In addition, no drug related adverse effects were observed in
      the two treatment groups. CONCLUSIONS: ETV and LAM treatments had similar effects
      to improve 24 weeks survival rate of patients with CHB-associated liver failure,
      but ETV was associated with greater clinical improvement. Both drugs were
      tolerated well during the treatment. It is suggested to perform further studies
      to verify the results.

PMID- 25598787
TI  - Risk Factors of Hepatitis C Virus Infection in Drug Users From Eleven Methadone
      Maintenance Treatment Clinics in Xi'an, China.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection rates in drug users vary among
      different regions of China. Drug users who are unaware of their HCV serostatus
      tend to engage in more risky behaviors. OBJECTIVES: This prospective study aimed
      to assess risk factors of HCV infection in drug users among 11 methadone
      maintenance treatment (MMT) clinics in Xi'an, China. PATIENTS AND METHODS:
      Baseline characteristics and drug use information of patients were collected upon
      enrollment in the study and anti-HCV tests were performed within one month after
      the enrollment. Data on daily medication, monthly random urine morphine test
      results, illicit drug use and MMT retention time were recorded during a 5-year
      follow-up. RESULTS: Of 10243 patients, 58.0% had positive results for anti-HCV.
      Injection drug use, longer duration of drug abuse, older age, female gender,
      unmarried status and unemployment were independent risk factors of HCV infection.
      Urine test positivity rate was lower (14.8% vs. 16.7%, chi(2) = 100.235, P <
      0.05), but MMT retention rate was higher (log-rank chi(2) = 4.397, P < 0.05) in
      the anti-HCV positive group than anti-HCV negative one. However, multivariate
      regression revealed no significant association between anti-HCV serostatus and
      either MMT retention time or illicit drug use. CONCLUSIONS: The major risk factor
      of HCV infection was injection drug use. The patient's awareness of his or her
      HCV status had a minor effect in reduction of illicit drug use and improvement in
      MMT retention. Therefore, adequate counseling is necessary for drug users in MMT
      clinics in Xi'an.

PMID- 25598788
TI  - Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana
      tabacum, a Protein With Potential Clinical Applications.
AB  - BACKGROUND: Hepatitis C virus (HCV) is major cause of liver cirrhosis in humans.
      HCV capsid (core) protein (HCVcp) is a highly demanded antigen for various
      diagnostic, immunization and pathogenesis studies. Plants are considered as an
      expression system for producing safe and inexpensive biopharmaceutical proteins.
      Although invention of transgenic (stable) tobacco plants expressing HCVcp with
      proper antigenic properties was recently reported, no data for "transient
      expression" that is currently the method of choice for rapid, simple and lower
      priced protein expression in plants is available for HCVcp. OBJECTIVES: The
      purpose of this study was to design a highly codon-optimized HCVcp gene for
      construction of an efficient transient-plant expression system for production of
      HCVcp with proper antigenic properties in a regional tobacco plant (Iranian
      Jafarabadi-cultivar) by evaluation of different classes of vectors and
      suppression of gene-silencing in tobacco. MATERIALS AND METHODS: A codon
      optimized gene encoding the Kozak sequence, 6xHis-tag, HCVcp (1-122) and KDEL
      peptide in tandem (from N- to C-terminal) was designed and inserted into potato
      virus-X (PVX) and classic pBI121 binary vectors in separate cloning reactions.
      The resulted recombinant plasmids were transferred into Agrobacterium tumefaciens
      and vacuum infiltrated into tobacco leaves. The effect of gene silencing
      suppressor P19 protein derived from tomato bushy stunt virus on the expression
      yield of HCVcp by each construct was also evaluated by co-infiltration in
      separate groups. The expressed HCVcp was evaluated by dot and western blotting
      and ELISA assays. RESULTS: The codon-optimized gene had an increased adaptation
      index value (from 0.65 to 0.85) and reduced GC content (from 62.62 to 51.05) in
      tobacco and removed the possible deleterious effect of "GGTAAG" splice site in
      native HCVcp. Blotting assays via specific antibodies confirmed the expression of
      the 15 kDa HCVcp. The expression level of HCVcp was enhanced by 4-5 times in P19
      co-agroinfiltrated plants with better outcomes for PVX, compared to pBI121 vector
      (0.022% versus 0.019% of the total soluble protein). The plant-derived HCVcp
      (pHCVcp) could properly identify the HCVcp antibody in HCV-infected human sera
      compared to Escherichia coli-derived HCVcp (eHCVcp), indicating its potential for
      diagnostic/immunization applications. CONCLUSIONS: By employment of gene
      optimization strategies, use of viral-based vectors and suppression of plant
      derived gene silencing effect, efficient transient expression of HCVcp in tobacco
      with proper antigenic properties could be possible.

PMID- 25598789
TI  - Association of hepcidin mRNA expression with hepatocyte iron accumulation and
      effects of antiviral therapy in chronic hepatitis C infection.
AB  - BACKGROUND: Iron overload is frequently observed in patients with chronic
      hepatitis C (CHC) and is associated with the increased risk of liver fibrosis and
      carcinogenesis. Hepcidin is a regulator of iron homeostasis and a component of
      innate immunity. Based on experimental studies, iron overload might be a result
      of low hepcidin synthesis in CHC. OBJECTIVES: The aim of this case-control study
      was to assess hepcidin mRNA expression in liver tissue of patients with CHC in
      terms of iron metabolism parameters, hemochromatosis (HFE) gene mutations,
      disease activity, and efficacy of antiviral treatment with pegylated interferon
      and ribavirin. PATIENTS AND METHODS: A total of 31 patients with CHC, who were
      qualified for antiviral therapy, were compared with 19 patients with chronic
      hepatitis B (CHB). In both groups, liver function tests and serum iron parameters
      were assayed and hepcidin mRNA expression was measured in liver specimens using
      real time PCR with normalization to reference genes mRNA of stable expression.
      RESULTS: Patients with CHC had lower hepcidin mRNA expression and more frequently
      iron deposits in hepatocytes than subjects with CHB did. In CHC group, hepcidin
      mRNA expression was positively correlated with alanine aminotransferase activity
      and serum iron concentration. Low expression of hepcidin had no correlation with
      tissue iron overload in those with CHC. In univariate analysis, HCV viral load
      and efficacy of antiviral treatment were not significantly associated with
      hepcidin mRNA expression. CONCLUSIONS: Further studies on the role of hepcidin in
      pathogenesis of CHC are needed to assess the potency of its use in antiviral
      treatment.

PMID- 25598790
TI  - Epidemiology of hepatitis B in the reproductive-age female farmworkers of
      southeastern Turkey.
AB  - BACKGROUND: There are limited data on the prevalence of the hepatitis B virus
      (HBV) infection in the agricultural population worldwide. OBJECTIVES: This study
      aimed to determine the prevalence of HBV infection and associated risk factors in
      the reproductive-age female farmworker. MATERIALS AND METHODS: This cross
      sectional study was conducted between January and April 2013 in southeastern
      region (SAR) of Turkey. A community-based representative agricultural sample (n =
      705) from the agricultural areas of nine provinces of SAR was randomly determined
      by clustering method using Epi Info software. Questionnaires including
      demographic information and risk factors of HBV were administered to
      participants. The presence of HBsAg, anti-HBs, anti-HBc, and anti-HBe antibodies
      in blood samples were measured by ELISA. RESULTS: The prevalence of the HBsAg,
      anti-HBs, anti-HBc, anti-HBe antibodies, and seropositivity were 5.7%, 25.9%,
      28.9%, 16.4%, and 36.7%, respectively. There was no association between the HBsAg
      and the size of the household, age, education level, parity, and place of birth
      while the prevalence of HBsAg was higher in seasonal migratory farmworkers and
      people living in urban areas and the prevalence of anti-HBs antibody was
      significantly higher in women >= 35 years of age, those with a high parity, and
      those who gave birth without the assistance of health professionals (P < 0.05).
      The risk for HBV infection in the seasonal migratory group was 4.3 times higher
      in comparison to local workers (P = 0.00; OR = 4.3; 95% CI, 2.2-8.4), with a
      prevalence rate of 11%. CONCLUSIONS: The monitoring of at-risk groups like
      seasonal migratory farmworkers is necessary to strengthen the healthcare service
      provided to this population.

PMID- 25598792
TI  - Characterization of HCV genotype 5a envelope proteins: implications for vaccine
      development and therapeutic entry target.
AB  - BACKGROUND: Hepatitis C virus (HCV) is one of the major causes of cirrhosis and
      hepatocellular carcinoma with an estimation of 185 million people with infection.
      The E2 is the main target for neutralizing antibody responses and the variation
      of this region is related to maintenance of persistent infection by emerging
      escape variants and subsequent development of chronic infection. While both E1
      and E2 are hypervariable in nature, it is difficult to design vaccines or
      therapeutic drugs against them. OBJECTIVES: The objective of this study was to
      characterize genotype 5a E1 and E2 sequences to determine possible glycosylation
      sites, conserved B-cell epitopes and peptides in HCV that could be useful targets
      in design of vaccine and entry inhibitors. PATIENTS AND METHODS: This study was
      conducted through PCR amplification of E1 and E2 regions, sequencing, prediction
      of B-cell epitopes, analysis of N-linked glycosylation and peptide design in 18
      samples of HCV genotype 5a from South African. RESULTS: Differences in the
      probability of glycosylation in E1 and E2 regions were observed in this study.
      Three conserved antigenic B-cell epitopes were predicted in the E2 regions and
      also 11 short peptides were designed from the highly conserved residues.
      CONCLUSIONS: This study provided conserved B-cell epitopes and peptides that can
      be useful for designing entry inhibitors and vaccines able to cover a global
      population, especially where genotype 5a is common.

PMID- 25598791
TI  - Are women with polycystic ovarian syndrome at a high risk of non-alcoholic Fatty
      liver disease; a meta-analysis.
AB  - CONTEXT: Insulin resistance is a hallmark of metabolic syndrome (MS). It has been
      proposed that both polycystic ovarian syndrome (PCOS) and nonalcoholic fatty
      liver disease (NAFLD) are correlated with Insulin resistance. Therefore, PCOS and
      NAFLD can be attributed with insulin resistance and therefore MS. The aim of this
      meta-analysis was to determine whether PCOS patients are at a high risk of NAFLD.
      EVIDENCE ACQUISITION: Google scholar, Scopus, ISI Web of Science, Embase,
      MEDLINE, and some Iranian databases such as scientific information database
      (SID), IranMedex, and MagIran were searched to identify relevant studies. We
      included all papers regardless of their language from January 1985 to June 2013.
      By using data on prevalence of NAFLD in patients with and without PCOS, odds
      ratio (OR) with 95% confidence intervals (CIs) were calculated in each study. Chi
      squared test was used to assess heterogeneity between studies. RESULTS: We
      finally included seven eligible studies. According to chi-squared test, there was
      a significant heterogeneity (73.6%) between studies (P = 0.001). NAFLD prevalence
      was significantly higher in patients with PCOS compared to healthy control, with
      an overall OR of 3.93 (95% CI: 2.17, 7.11).There was no significant publication
      bias based on Begg's and Egger's tests. CONCLUSIONS: According to the results of
      this meta-analysis, there was a high risk of NAFLD in women with PCOS. We suggest
      evaluating patients with PCOS regarding NAFLD.

PMID- 25598793
TI  - Sofosbuvir vs. Combination of Pegylated Interferon and Ribavirin; How Much Shall
      Pay for Iranian Patients?

PMID- 25598794
TI  - Micellar stabilized single-walled carbon nanotubes for a pH-sensitive delivery of
      doxorubicin.
AB  - Single-walled carbon nanotubes (SWNTs) are among the promising nano-devices for
      delivery of therapeutic agents. Yet the drastic hydrophobic natures of SWNTs make
      their handling and hence application difficult. Several researches have been
      conducted to make them more hydrophilic and water dispersible and less toxic.
      Among the different approaches, dispersion methods exploit different reagents
      such as surfactants and block copolymers. The question is whether these so called
      dispersed SWNTs are stable enough and suitable for biomedical applications.
      Herein we aimed to functionalize SWNT surface by dioleoylphosphatidylethanolamine
      polyethylene glycol (PL-PEG) and sodium deoxycholate (SDC) micelles and compare
      their efficacy in SWNT stabilization for biomedical application such as delivery
      of doxorubicin. Shortening and water dispersion of SWNTs were carried out by
      ultrasonication in aqueous solutions at different concentrations of SDC or PL-PEG
      micelle and assessed by UV-Vis-NIR spectroscopy. The stability of SWNT
      dispersions were assessed over the time and in the presence of salt by
      macroscopic observation and UV-Vis-NIR spectroscopy. Doxorubicin loading and
      release were carried out under different pH conditions. SWNT dispersions were
      stable in water for at least several weeks at room temperature, but SDC prepared
      dispersions were prone to agglomeration in the presence of salt and doxorubicin.
      The critical PL-PEG concentration for stability in physiologic conditions was
      about 5 times its critical micelle concentration. Doxorubicin loading was pH
      dependent and its release was triggered in acidic condition of tumor medium. 

PMID- 25598796
TI  - Radioprotective effect of sulphydryl group containing triazole derivative to
      modulate the radiation- induced clastogenic effects.
AB  - Protection of biological systems against radiation damage is of paramount
      importance during accidental and unavoidable exposure to radiation. Several
      physico-chemical and biological factors collectively contribute to the damage
      caused by radiation and are, therefore, targets for developing radioprotectors.
      Chemicals capable of scavenging free radicals, relieving oxidative stress,
      promoting antioxidant activity and modulating immune response have been some of
      the radioprotectors extensively investigated with limited success. It has long
      been known that some of the most effective radioprotective agents are those which
      contain sulphydryl groups. 4-amino-5-mercapto-3-methyl-1, 2, 4-triazole (AMMT) is
      one of the well-known 1, 2, 4 triazole derivatives with functional sulphydryl
      group. The present study reports an evaluation of radical scavenging and
      radioprotective properties of sulphydryl group containing triazole derivative.
      The lethal dose of electron beam radiation (EBR) was studied by survival assay.
      The dose reduction factor (DRF) of AMMT was calculated using the ratio between
      LD50 of EBR with and without AMMT treatment. Radical scavenging property of AMMT
      was assessed by DPPH radical scavenging assay. The clastogenic effects of EBR
      were recorded by Micronucleus test in bone marrow cells and DNA fragmentation
      assay in mice hepatic cells. The survival assay results showed that the LD50 of
      EBR was 10 Gy. The calculated DRF for AMMT was found to be 1.2. DPPH radical
      scavenging assay showed a positive result when it was compared with the standard
      glutathione. Treatment of mice with 100 mg of AMMT for 15 days before irradiation
      significantly (P<0.05) reduced the frequency of micronucleus formation in bone
      marrow cells and also reduced the DNA fragmentation in hepatic cells. The results
      obtained in the present study indicated that AMMT has a protective effect against
      the EBR-induced mortality and clastogenicity. 

PMID- 25598795
TI  - In vitro antidiabetic potential of the fruits of Crataegus pinnatifida.
AB  - In an attempt to develop alternative medicine for the treatment of diabetes and
      related complications, the antidiabetic potential of the fruits of Crataegus
      pinnatifida was evaluated. The antidiabetic potential of the methanol (MeOH)
      extract as well as different solvent soluble fractions of the fruits of C.
      pinnatifida was evaluated via alpha-glucosidase, protein tyrosine phosphatase 1B
      (PTP1B), rat lens aldose reductase (RLAR), and advanced glycation end products
      (AGEs) formation inhibitory assays. The MeOH extract showed potent inhibitory
      activity against alpha-glucosidase, PTP1B, and AGEs formation with IC50 values of
      122.11, 3.66 and 65.83 MUg/ml respectively, while it showed moderate inhibitory
      activity against RLAR with the IC50 value of 160.54 MUg/ml. Among different
      fractions, the ethyl acetate (EtOAc) and the dichloromethane (CH2Cl2) fractions
      were found as active fractions exhibiting potential alpha-glucosidase, PTP1B,
      RLAR inhibitory, and AGEs formation inhibitory activities. Seven compounds
      including hyperoside, chlorogenic acid, ursolic acid, oleanolic acid, 3
      epicorosolic acid, beta-sitosterol, beta-sitosterol glucoside were isolated from
      these two fractions. 3-Epicorosolic acid showed both potent alpha-glucosidase and
      PTP1B inhibitory activities with IC50 values of 30.18 and 4.08 MUg/ml
      respectively. Moreover, kinetic study revealed that 3-epicorosolic acid showed
      mixed type inhibition against PTP1B, while it showed uncompetitive inhibition
      against alpha-glucosidase. Therefore, these results suggest that the fruits of C.
      pinnatifida and its constituents have potential antidiabetic activity which might
      be used as a functional food for the treatment of diabetes and associated
      complications. 

PMID- 25598797
TI  - Analysis of phenolic compounds in Matricaria chamomilla and its extracts by UPLC
      UV.
AB  - Chamomile (Matricaria chamomilla L.) is a widely used medicinal plant possessing
      several pharmacological effects due to presence of active compounds. This study
      describes a method of using ultra performance liquid chromatography (UPLC)
      coupled with photodiode array (PDA) detector for the separation of phenolic
      compounds in M. chamomilla and its crude extracts. Separation was conducted on
      C18 column (150 mm * 2 mm, 1.8 MUm) using a gradient elution with a mobile phase
      consisting of acetonitrile and 4% aqueous acetic acid at 25 degrees C. The method
      proposed was validated for determination of free and total apigenin and apigenin
      7-glucoside contents as bioactive compounds in the extracts by testing
      sensitivity, linearity, precision and recovery. In general, UPLC produced
      significant improvements in method sensitivity, speed and resolution. Extraction
      was performed with methanol, 70% aqueous ethanol and water solvents. Total
      phenolic and total flavonoid contents ranged from 1.77 to 50.75 gram (g) of
      gallic acid equivalent (GAE)/100 g and 0.82 to 36.75 g quercetin equivalent
      (QE)/100 g in dry material, respectively. There was a considerable difference
      from 40 to 740 mg/100 g for apigenin and 210 to 1110 mg/100 g for apigenin 7
      glucoside in dry material. 

PMID- 25598798
TI  - Evaluation of Calendula mucilage as a mucoadhesive and controlled release
      component in buccal tablets.
AB  - Mucoadhesive drug delivery systems were developed to sustain drug delivery via
      various mucus membranes for either local or systemic delivery of poorly absorbed
      drugs such as peptides and proteins as well as drugs that are subjected to high
      first-pass metabolism. The present study was undertaken to use isolated Calendula
      mucilage as a mucoadhesive agent and to formulate controlled release
      buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as
      well as to enhance residence time of drug in the buccal cavity. The mucilage was
      isolated from the Calendula petals by aqueous extraction method and characterized
      for various physiochemical parameters as well as for its adhesive properties. By
      using direct compression technique, tablets were prepared containing dried
      mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of
      tablets were prepared and evaluated containing three mucoadhesive components
      namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%,
      33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR
      studies between mucilage and CPM suggested the absence of a chemical interaction
      between CPM and Calendula mucilage. The results of the study showed that the
      isolated mucilage had good physicochemical and morphological characteristics and
      tablets conformed to the pharmacopoeial specifications. Also in vitro release
      studies showed controlled action of drug with increasing the concentration of the
      isolated Calendula mucilage as a mucoadhesive agent in the formulations.
      Permeability studies indicated that permeability behavior was not statistically
      different (P>0.05) by changing the mucoadhesive component. The formulated
      mucoadhesive tablets for buccal administration containing 75 mg Calendula
      mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula
      mucilage based buccal tablets for controlled release were successfully
      formulated. 

PMID- 25598799
TI  - Salinity alters curcumin, essential oil and chlorophyll of turmeric (Curcuma
      longa L.).
AB  - Turmeric (Curcuma longa L.) is a perennial rhizomatous plant from the family of
      Zingibraceae, native in South Asia. The main components of turmeric are
      curcuminoids and essential oil which are responsible for turmeric characteristic
      such as odor and taste. Due to the large areas of saline land in Iran and less
      information related to cultivation of turmeric, in this research, the effect of
      salinity on growth, curcumin and essential oil of turmeric was evaluated.
      Rhizomes were planted in coco peat and perlite for germination. Then uniform
      germinated rhizomes transferred to hydroponic condition containing Hoagland's
      solution. Two months old plants were exposed to salinity (0, 20, 60 and 100 mM
      NaCl) for two months via hydroponic media using Hoagland's solution. Then dry
      weight of different plant parts, chlorophyll, curcumin and essential oil
      components of turmeric were determined. The result indicated that, dry weight
      reductions in 100 mM NaCl were 191%, 141%, 56%, 30% in leaf, pseudo-stem, root
      and rhizome, respectively (This is almost equal to 6.9, 2.87, 0.34 and 0.23 mg
      plant(-1) mM(-1)NaCl reduction of dry weight, respectively). The reductions in
      chlorophyll a and b are almost 3.32 and 0.79 MUg/gFW respectively due to one unit
      addition of NaCl (P < 0.05). The addition of curcumin of rhizome for four months
      old plant versus three months were almost 5 fold for 0 mM NaCl and 2 fold for 100
      mM NaCl due to one month of delay in harvest. Low salinity has positive effect in
      curcumin production but higher salinity (higher than 60 mM) had adverse effect
      and causes 24% reduction of curcumin compared to control plants. There were more
      para-cymene and terpineol in volatile oils of turmeric rhizome than the other
      components, most of the volatile oil compounds were unchanged or varied slightly
      as salinity changed. 

PMID- 25598800
TI  - In vivo pharmacological profile of substituted (3-pyridyl)-2-phenylisoxazolidine
      analogues of nicotine as novel antinociceptives.
AB  - Nicotinic ligands have been studied as novel therapeutic interventions in pain
      therapeutics since a long time. Several nicotinic agonists have been withdrawn
      from later stages of clinical trials due to lack of efficacy or narrow
      therapeutic window. These have been documented to act in the central nervous
      system and produce a wide range of pharmacological effects, including memory
      enhancing and analgesic actions, antianxiety, antidepressant and muscle
      coordination. Taking cognizance of the wide pharmacological profile of nicotine
      and its ligands, it was decided to evaluate some novel isoxazolidine analogues of
      nicotine for their potential as analgesics, using animal models like Eddy's hot
      plate and Tail immersion method. The compounds showed marked decrease in
      hyperalgesic response as compared to pentazocine at a wide range of doses. They
      were well tolerated as none of the compounds was found to have any seizure
      potential or mortality even at the highest doses. Thus, these compounds can be
      developed as potent antinociceptives with better safety profile than nicotine and
      other currently available pain therapeutics. 

PMID- 25598801
TI  - Design of a novel metal binding peptide by molecular dynamics simulation to
      sequester Cu and Zn ions.
AB  - Heavy metal toxicity has serious adverse effects on the environment. The metal
      sequestering characteristics of a novel metal binding peptide (Glu-Cys)11
      Gly+linker+hexahistidine (EC11:His6) was investigated to determine if it can
      absorb Cu(2+) or Zn(2+) cations. Molecular dynamics simulations were carried out
      using a model of 6 Cu(2+) or Zn(2+) and other ions enclosed in a fully hydrated
      simulation box with the designed peptide. Totally, 240 nano second (ns)
      simulations were done in three phases. Results showed that the selected linker is
      able to separate two domains of this peptide and that the carboxyl oxygens of Glu
      residues of EC11 in the designed peptide can absorb these ions. Sequestration of
      Cu(2+) or Zn(2+) ions by the designed peptide does not change overall tertiary
      and secondary structures of peptide. 

PMID- 25598802
TI  - Agonistic and Antagonistic Interactions between Chlorhexidine and Other
      Endodontic Agents: A Critical Review.
AB  - Root canal irrigants play a significant role in elimination of the
      microorganisms, tissue remnants, and removal of the debris and smear layer. No
      single solution is able to fulfill all these actions completely; therefore, a
      combination of irrigants may be required. The aim of this investigation was to
      review the agonistic and antagonistic interactions between chlorhexidine (CHX)
      and other irrigants and medicaments. An English-limited Medline search was
      performed for articles published from 2002 to 2014. The searched keywords
      included: chlorhexidine AND sodium hypochlorite/ethylenediaminetetraacetic
      acid/calcium hydroxide/mineral trioxide aggregate. Subsequently, a hand search
      was carried out on the references of result articles to find more matching
      papers. Findings showed that the combination of CHX and sodium hypochlorite
      (NaOCl) causes color changes and the formation of a neutral and insoluble
      precipitate; CHX forms a salt with ethylenediaminetetraacetic acid (EDTA). In
      addition, it has been demonstrated that the alkalinity of calcium hydroxide (CH)
      remained unchanged after mixing with CHX. Furthermore, mixing CHX with CH may
      enhance its antimicrobial activity; also mixing mineral trioxide aggregate (MTA)
      powder with CHX increases its antimicrobial activity but this may negatively
      affect its mechanical properties. 

PMID- 25598805
TI  - Effect of Different pH Values on the Compressive Strength of Calcium-Enriched
      Mixture Cement.
AB  - INTRODUCTION: The aim of this study was to evaluate the compressive strength of
      calcium-enriched mixture (CEM) cement in contact with acidic, neutral and
      alkaline pH values. METHODS AND MATERIALS: The cement was mixed according to the
      manufacturer's instructions, it was then condensed into fourteen split molds with
      five 4*6 mm holes. The specimens were randomly divided into 7 groups (n=10) and
      were then exposed to environments with pH values of 4.4, 5.4, 6.4, 7.4, 8.4, 9.4
      and 10.4 in an incubator at 37( degrees ) C for 4 days. After removing the
      samples from the molds, cement pellets were compressed in a universal testing
      machine. The exact forces required for breaking of the samples were recorded. The
      data were analyzed with the Kruskal-Wallis and Dunn tests for individual and
      pairwise comparisons, respectively. The level of significance was set at 0.05.
      RESULTS: The greatest (48.59+/-10.36) and the lowest (9.67+/-3.16) mean
      compressive strength values were observed after exposure to pH value of 9.4 and
      7.4, respectively. Alkaline environment significantly increased the compressive
      strength of CEM cement compared to the control group. There was no significant
      difference between the pH values of 9.4 and 10.4 but significant differences were
      found between pH values of 9.4, 8.4 and 7.4. The acidic environment showed better
      results than the neutral environment, although the difference was not significant
      for the pH value of 6.4. Alkaline pH also showed significantly better results
      than acidic and neutral pH. CONCLUSION: The compressive strength of CEM cement
      improved in the presence of acidic and alkaline environments but alkaline
      environment showed the best results.

PMID- 25598806
TI  - A new simulated plasma for assessing the solubility of mineral trioxide
      aggregate.
AB  - INTRODUCTION: Solubility of mineral trioxide aggregate (MTA) is an important
      characteristic that affects other properties such as microleakage and
      biocompatibility. Distilled water (DW) has previously been used for solubility
      tests. This experimental study compared the solubility of MTA in DW, synthetic
      tissue fluid (STF) and new simulated plasma (SP). METHODS AND MATERIALS: In this
      study, 36 samples of tooth-colored ProRoot MTA were prepared and divided into
      three groups (n=12) to be immersed in three different solutions (DW, STF, and
      SP). Solubility tests were conducted at 2, 5, 9, 14, 21, 30, 50, and 78-day
      intervals. The unequal variance F-test (Welch test) was utilized to determine the
      effect of solubility media and Games-Howell analysis was used for pairwise
      comparisons. The repeated-measures ANOVA was used to assess the importance of
      immersion duration. RESULTS: Welch test showed significant differences in
      solubility rates of samples between all the different solubility media at all the
      study intervals (P<0.05) except for the 14-day interval (P=0.094). The mixed
      repeated-measures ANOVA revealed a significant difference in solubility rate of
      MTA in three different solutions at all time-intervals (P=0.000). Games-Howell
      post-hoc test revealed that all pairwise comparisons were statistically
      significant at all time-intervals (P=0.000). CONCLUSION: Based on the findings of
      this study, the long-term solubility of MTA in simulated plasma was less than
      that in synthetic tissue fluid and distilled water.

PMID- 25598803
TI  - A review on vital pulp therapy in primary teeth.
AB  - Maintaining deciduous teeth in function until their natural exfoliation is
      absolutely necessary. Vital pulp therapy (VPT) is a way of saving deciduous
      teeth. The most important factors in success of VPT are the early diagnosis of
      pulp and periradicular status, preservation of the pulp vitality and proper
      vascularization of the pulp. Development of new biomaterials with suitable
      biocompatibility and seal has changed the attitudes towards preserving the
      reversible pulp in cariously exposed teeth. Before exposure and irreversible
      involvement of the pulp, indirect pulp capping (IPC) is the treatment of choice,
      but after the spread of inflammation within the pulp chamber and establishment of
      irreversible pulpitis, removal of inflamed pulp tissue is recommended. In this
      review, new concepts in preservation of the healthy pulp tissue in deciduous
      teeth and induction of the reparative dentin formation with new biomaterials
      instead of devitalization and the consequent destruction of vital tissues are
      discussed. 

PMID- 25598807
TI  - Anterior traumatic dental injuries in East Iranian school children: prevalence
      and risk factors.
AB  - INTRODUCTION: The aim of this cross-sectional study was to determine the
      prevalence and etiology of traumatic dental injuries (TDI) in school children of
      the Northeast of Iran. The type of involved teeth, the place of injury and
      treatment quality as well as the relationship between TDI and anatomic
      predisposing factors such as overjet and lip coverage were evaluated. METHODS AND
      MATERIALS: A total of 778 school children were clinically examined for signs of
      trauma to their permanent teeth and the amount of overjet and lip coverage were
      also recorded. A questionnaire containing demographic data of participants and
      history of the dental trauma was given to the children's parents. The data were
      analyzed using the chi-square and Mann-Whitney tests. RESULTS: One hundred and
      seventy eight (22.9%) children had a history of previous trauma to their
      permanent teeth. There was a significant difference between boys and girls
      (P=0.017). A total of 46.1% of children had experienced luxation injuries of
      permanent teeth, 37% had crown fractures, and 16.9% experienced avulsion of
      anterior teeth. Maxillary central incisors were the most commonly affected teeth
      (84%). There was a significant relationship between TDI and overjet (P=0.02) in
      permanent teeth. On the other hand, there was no statistically significant
      relationship between TDI and lip coverage. The most common cause of TDI was
      falling over (42.9%) followed by fighting (34%). The majority of traumas happened
      at home (46.8%) and school (29.9%). Sixty two (39.7%) children with TDI did not
      receive any dental or medical care after injury. CONCLUSION: The prevalence of
      dental trauma in school children in Iran was rather high (22.9%); the most common
      type of trauma to the permanent teeth was luxation injuries.

PMID- 25598804
TI  - The applications of cone-beam computed tomography in endodontics: a review of
      literature.
AB  - By producing undistorted three-dimensional images of the area under examination,
      cone-beam computed tomography (CBCT) systems have met many of the limitations of
      conventional radiography. These systems produce images with small field of view
      at low radiation doses with adequate spatial resolution that are suitable for
      many applications in endodontics from diagnosis to treatment and follow-up. This
      review article comprehensively assembles all the data from literature regarding
      the potential applications of CBCT in endodontics. 

PMID- 25598808
TI  - Antimicrobial Activity of Nanoparticle Calcium Hydroxide against Enterococcus
      Faecalis: An In Vitro Study.
AB  - INTRODUCTION: Enterococcus faecalis (E. faecalis) has the ability to invade the
      dentinal tubules and resist high pH levels. As a result, calcium hydroxide (CH)
      is not much effective on this bacterium. In theory, nanoparticle calcium
      hydroxide (NCH) has smaller size and high surface area that enables it to
      penetrate into the deeper layers of dentin and be more effective on E. faecalis.
      This in vitro study was designed to compare the antimicrobial activity of NCH and
      CH against E. faecalis. METHODS AND MATERIALS: The antimicrobial activity of NCH
      against E. faecalis was evaluated by two independent tests: the minimum
      inhibitory concentration (MIC) of intracanal medicament and agar diffusion test
      (ADT). The efficiency of the medicament in dentinal tubules was evaluated on 23
      human tooth blocks that were inoculated with E. faecalis. The tooth blocks were
      assigned to one control group (saline irrigation) and two experimental groups
      receiving CH and NCH as intracanal medication. The optical density in each group
      was assessed with spectrophotometer after collecting samples from dentin depths
      of 0, 200 and 400 um. Data were analyzed by SPSS software ANOVA, Kruskal-Wallis
      and Dunnett's test. RESULTS: The MIC for NCH was 1/4 of the MIC for CH. NCH with
      distilled water (DW) produced the greatest inhibition zone in agar diffusion
      test. NCH had greater antimicrobial activity in dentin samples from depths of 200
      and 400 um compared to CH. CONCLUSION: The antimicrobial activity of NCH was
      superior to CH in culture medium. In dentinal tubules the efficacy of NCH was
      again better than CH on the 200- and 400-um samples.

PMID- 25598809
TI  - A CBCT Assessment of Apical Transportation in Root Canals Prepared with Hand K
      Flexofile and K3 Rotary Instruments.
AB  - INTRODUCTION: Apical transportation changes the physical shape and physiologic
      environment of the root canal terminus. The aim of the present experimental study
      was to determine the extent of apical transportation after instrumentation with
      hand K-Flexofile and K3 rotary instruments by means of cone-beam computed
      tomography (CBCT). METHODS AND MATERIALS: Forty mesiobuccal root canals of
      maxillary first molars, with 19-22 mm length and 20-40( degrees ) canal
      curvature, were selected and assigned into two preparation groups. The first
      group was prepared with K-Flexofile with passive step-back technique and the
      second group was prepared with K3 rotary instruments. Pre and post
      instrumentation CBCT images were taken under similar conditions. The amount of
      root canal transportation was evaluated by Mann-Whitney U test and the chi-square
      test was used for the qualitative evaluation. RESULTS: The amounts of apical
      canal transportation with the K3 and K-Flexofile instruments were 0.105+/-0.088
      and 0.150+/-0.127 mm, respectively with no statistically significant differences.
      In the manual technique, 25% of the canals had no apical transportation; while
      30% of the canals in the K3 group were transportation free. CONCLUSION: Both
      systems were able to preserve the initial curvature of the canals and both had
      sufficient accuracy. Preparation with K3 rotary instruments resulted in apical
      transportation similar to that of K-Flexofile.

PMID- 25598810
TI  - Toxicity of calcium hydroxide nanoparticles on murine fibroblast cell line.
AB  - INTRODUCTION: One of the major contributing factors, which may cause failure of
      endodontic treatment, is the presence of residual microorganisms in the root
      canal system. For years, most dentists have been using calcium hydroxide (CH) as
      the intracanal medicament between treatment sessions to eliminate remnant
      microorganisms. Reducing the size of CH particles into nanoparticles enhances the
      penetration of this medicament into dentinal tubules and increases their
      antimicrobial efficacy. This in vitro study aimed to compare the cytotoxicity of
      CH nanoparticles and conventional CH on fibroblast cell line using the Mosmann's
      Tetrazolium Toxicity (MTT) assay. METHODS AND MATERIALS: This study was conducted
      on L929 murine fibroblast cell line by cell culture and evaluation of the direct
      effect of materials on the cultured cells. Materials were evaluated in two groups
      of 10 samples each at 24, 48 and 72 h. At each time point, 10 samples along with
      5 positive and 5 negative controls were evaluated. The samples were transferred
      into tubes and exposed to fibroblast cells. The viability of cells was then
      evaluated. The Two-way ANOVA was used for statistical analysis and the level of
      significance was set at 0.05. RESULTS: Cytotoxicity of both materials decreased
      over time and for conventional CH was lower than that of nanoparticles. However,
      this difference was not statistically significant (P>0.05). CONCLUSION: The
      cytotoxicity of CH nanoparticles was similar to that of conventional CH.

PMID- 25598811
TI  - The effect of different mixing methods on the flow rate and compressive strength
      of mineral trioxide aggregate and calcium-enriched mixture.
AB  - INTRODUCTION: Flow rate (FR) and compressive strength (CS) are important
      properties of endodontic biomaterials that may be affected by various mixing
      methods. The aim of this experimental study was to evaluate the effect of
      different mixing methods on these properties of mineral trioxide aggregate (MTA)
      and calcium-enriched mixture (CEM) cement. MATERIALS AND METHODS: Hand,
      amalgamator and ultrasonic techniques were used to mix both biomaterials. Then
      0.5 mL of each mixture was placed on a glass slab to measure FR. The second glass
      slab (100 g) was placed on the samples and 180 sec after the initiation of mixing
      a 100-g force was applied on it for 10 min. After 10 min, the load was removed,
      and the minimum and maximum diameters of the sample disks were measured. To
      measure the CS, 6 sample of each group were placed in steel molds and were then
      stored in distilled water for 21 h and 21 days. Afterwards, the CS test was
      performed. Data were analyzed with multi-variant ANOVA and post hoc Tukey tests.
      The level of significance was set at 0.05. RESULTS: There were significant
      differences in FR of MTA and CEM cement with different mixing techniques
      (P<0.05). In the MTA group, none of the mixing techniques exhibited a significant
      effect on CS (P>0.05); however, in CEM group the CS at 21-h and 21-day intervals
      was higher with the hand technique (P<0.05). CONCLUSION: Mixing methods affected
      the flowability of both biomaterials and compressive strength of CEM cement.

PMID- 25598812
TI  - The effect of chlorhexidine on the push-out bond strength of calcium-enriched
      mixture cement.
AB  - INTRODUCTION: The aim of this in vitro study was to evaluate the effect of 2%
      chlorhexidine (CHX) on the push-out bond strength (BS) of calcium-enriched
      mixture (CEM) cement. METHODS AND MATERIALS: Root-dentin slices from 60 single
      rooted human teeth with the lumen diameter of 1.3 mm were used. The samples were
      randomly divided into 4 groups (n=15), and their lumens were filled with CEM
      cement mixed with either its specific provided liquid (groups 1 and 3) or 2% CHX
      (groups 2 and 4). The specimens were incubated at 37( degrees )C for 3 days
      (groups 1 and 2) and 21 days (groups 3 and 4). The push-out BS were measured
      using a universal testing machine. The slices were examined under a light
      microscope at 40* magnification to determine the nature of bond failure. The data
      were analyzed using the two-way ANOVA. For subgroup analysis the student t-test
      was applied. The level of significance was set at 0.05. RESULTS: After three
      days, there was no significant difference between groups 1 and 2 (P=0.892). In
      the 21-day specimens the BS in group 3 (CEM) was significantly greater than group
      4 (CEM+CHX) (P=0.009). There was no significant difference in BS between 3 and 21
      day samples in groups 2 and 4 (CEM+CHX) (P=0.44). However, the mean BS after 21
      days was significantly greater compared to 3-day samples in groups 1 and 3
      (P=0.015). The bond failure in all groups was predominantly of cohesive type.
      CONCLUSION: Mixing of CEM with 2% CHX had an adverse effect the bond strength of
      this cement.

PMID- 25598813
TI  - Fluoride varnish as root canal sealer: a scanning electron microscopy and
      bacterial penetration study.
AB  - INTRODUCTION: This study was carried out to evaluate the bacterial leakage of
      root canal fillings when cavity varnish containing 5% fluoride (Duraflur) was
      used as root canal sealer. METHODS AND MATERIALS: Root canals of 88 straight
      single-rooted teeth were prepared. Eighty teeth were randomly divided into 3
      experimental groups (n=20) and two positive and negative control groups of ten
      each. The roots in group I and II were obturated with gutta-percha and AH-26
      sealer using lateral condensation technique. The root canal walls in group II
      were coated with a layer of varnish before obturation. In group III the canals
      were obturated with gutta-percha and fluoride varnish as the sealer. Enterococcus
      faecalis (E. faecalis) was used to determine the bacterial leakage during 90
      days. The Kaplan Meier survival analysis was used for assessing the leakage and
      log rank test was used for pairwise comparison. The rest of eight single rooted
      teeth were selected for scanning electron microscopy (SEM) evaluation with 5000*
      magnification. RESULTS: Leakage occurred between 20 to 89 days. Group III showed
      significantly less bacterial penetration than groups I and II (P=0.001 and
      P=0.011, respectively). However, there was no significant difference between
      group I and II (P>0.05). SEM evaluation showed that the varnish had covered all
      dentinal tubules. CONCLUSION: The present study showed promising results for the
      use of fluoride varnish as root canal sealer but further in vitro and in vivo
      studies are needed.

PMID- 25598814
TI  - CBCT Evaluation of the Root Canal Filling Removal Using D-RaCe, ProTaper
      Retreatment Kit and Hand Files in curved canals.

PMID- 25598815
TI  - Nonsurgical management of an extensive perforative internal root resorption with
      calcium-enriched mixture cement.
AB  - Internal inflammatory root resorption (IIRR) is a rare condition of the root
      canal and if it is left untreated it may lead to destruction of the surrounding
      dental hard tissues. Odontoclasts are responsible for this situation which can
      potentially perforate the root. Many initiating factors have been mentioned for
      IIRR, almost all causing chronic inflammation in the vital pulp. IIRR is usually
      symptom free, but in cases of root perforation, a sinus tract usually forms. The
      prognosis of treatment depends on the size of lesion with small lesions being
      managed with good prognosis. However, in case of notable destruction of the
      tooth, the prognosis is poor and tooth extraction may become inevitable. This
      report represents the management of an extensive perforative IIRR that was
      successfully sealed with calcium-enriched mixture (CEM) cement. After 12 months
      the tooth was still symptomless and in function. 

PMID- 25598816
TI  - Apexification in non-vital teeth with immature roots: report of two cases.
AB  - Apexification is a method of inducing apical closure for non-vital immature
      permanent teeth. During this treatment a mineralized barrier is induced [with
      long term calcium hydroxide (CH) treatment]; or artificially created [with
      mineral trioxide aggregate (MTA) plug]. This article describes two cases of
      apexification in immature necrotic teeth treated with these two different
      techniques. After 6 years of follow-up, clinical and radiographic control showed
      that both treatments were successful. 

PMID- 25598817
TI  - Friends who have the same dream walk together.

PMID- 25598818
TI  - For the future of Asia collaboration.

PMID- 25598819
TI  - The many faces of dissociation: opportunities for innovative research in
      psychiatry.
AB  - It has been claimed that the progress of psychiatry has lagged behind that of
      other medical disciplines over the last few decades. This may suggest the need
      for innovative thinking and research in psychiatry, which should consider
      neglected areas as topics of interest in light of the potential progress which
      might be made in this regard. This review is concerned with one such field of
      psychiatry: dissociation and dissociative disorders. Dissociation is the ultimate
      form of human response to chronic developmental stress, because patients with
      dissociative disorders report the highest frequency of childhood abuse and/or
      neglect among all psychiatric disorders. The cardinal feature of dissociation is
      a disruption in one or more mental functions. Dissociative amnesia,
      depersonalization, derealization, identity confusion, and identity alterations
      are core phenomena of dissociative psychopathology which constitute a single
      dimension characterized by a spectrum of severity. While dissociative identity
      disorder (DID) is the most pervasive condition of all dissociative disorders,
      partial representations of this spectrum may be diagnosed as dissociative amnesia
      (with or without fugue), depersonalization disorder, and other specified
      dissociative disorders such as subthreshold DID, dissociative trance disorder,
      acute dissociative disorders, and identity disturbances due to exposure to
      oppression. In addition to constituting disorders in their own right,
      dissociation may accompany almost every psychiatric disorder and operate as a
      confounding factor in general psychiatry, including neurobiological and psycho
      pharmacological research. While an anti- dissociative drug does not yet exist,
      appropriate psychotherapy leads to considerable improvement for many patients
      with dissociative disorders. 

PMID- 25598820
TI  - Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for
      major depressive disorder: a double blind, randomised, placebo controlled trial.
AB  - While current pharmacotherapies are efficacious, there remain a clear shortfall
      between symptom remission and functional recovery. With the explosion in our
      understanding of the biology of these disorders, the time is ripe for the
      investigation of novel therapies. Recently depression is conceptualized as an
      immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a
      tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic,
      neurotrophic and neuroprotective properties that make it a viable target to
      explore as a new therapy. This double blind, randomised, placebo controlled
      adjunctive trial will investigate the benefits of 200 mg/day of minocycline
      treatment, in addition to any usual treatment, as an adjunctive treatment for
      moderate-severe major depressive disorder. Sixty adults are being randomised to
      12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary
      outcome measure for the study is mean change on the Montgomery-Asberg Depression
      Rating Scale (MADRS), with secondary outcomes including the Social and
      Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions
      (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression
      (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and
      Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be
      conducted at baseline and week 12. The study has the potential to provide new
      treatment targets, both by showing efficacy with a new class of 'antidepressant'
      but also through the analysis of biomarkers that may further inform our
      understanding of the pathophysiology of unipolar depression. 

PMID- 25598821
TI  - Are Auditory Hallucinations Related to the Brain's Resting State Activity? A
      'Neurophenomenal Resting State Hypothesis'.
AB  - While several hypotheses about the neural mechanisms underlying auditory verbal
      hallucinations (AVH) have been suggested, the exact role of the recently
      highlighted intrinsic resting state activity of the brain remains unclear. Based
      on recent findings, we therefore developed what we call the 'resting state
      hypotheses' of AVH. Our hypothesis suggest that AVH may be traced back to
      abnormally elevated resting state activity in auditory cortex itself, abnormal
      modulation of the auditory cortex by anterior cortical midline regions as part of
      the default-mode network, and neural confusion between auditory cortical resting
      state changes and stimulus-induced activity. We discuss evidence in favour of our
      'resting state hypothesis' and show its correspondence with phenomenal, i.e.,
      subjective-experiential features as explored in phenomenological accounts.
      Therefore I speak of a 'neurophenomenal resting state hypothesis' of auditory
      hallucinations in schizophrenia. 

PMID- 25598822
TI  - Serotonin and mental disorders: a concise review on molecular neuroimaging
      evidence.
AB  - Serotonin is one of the most important neurotransmitters influencing mental
      health and, thus, is a potential target for pharmaco-logical treatments.
      Functional neuroimaging techniques, such as positron-emission tomography (PET)
      and single photon emission computed tomography (SPECT), could provide persuasive
      evidence for the association between mental disorders and serotonin. In this
      concise review, we focus on evidence of the links between serotonin and major
      depressive disorders, as well as other mood disorders, anxiety disorders,
      schizophrenia, addiction, attention deficit hyperactivity disorder (ADHD), and
      autism. 

PMID- 25598823
TI  - Executive Dysfunction among Children with Antipsychotic Treated Schizophrenia.
AB  - OBJECTIVE: To investigate the executive function among adolescents with
      antipsychotic-treated schizophrenia in Child and Adolescent Outpatient Clinic at
      Cipto Mangunkusumo General Hospital, Jakarta. METHODS: This was a cross sectional
      study with control group. Case was defined as adolescents with antipsychotic
      treated schizophrenia without any mental retardation or other physical illnesses
      (n=45). The control group consisted of healthy and age-matched adolescents
      (n=135). Executive function is determined by using Indonesian version of Behavior
      Rating Inventory of Executive Function (BRIEF-Indonesian version). We used SPSS
      16.0 program for windows to calculate the prevalence risk ratio (PRR) and set up
      the p value <0.05. RESULTS: Mean of age was 16.27 (standard deviation 1.86) year
      old. Most of the case group (95%) has been treated with atypical antipsychotic
      such as risperidone, aripipripazole, olanzapine, and clozapine. Duration of
      having antipsychotic medication was ranged from one to 36 months. Adolescents
      with antipsychotic treated-schizophrenia had higher BRIEF T-score, except for
      inhibit scale, shift scale and behavior regulation index. The prevalence risk
      ratio on several clinical scales were higher in children with antipsychotic
      treated schizophrenia compared to control group, such as on emotional state
      (PRR=7.43, 95% confidence interval [CI]=2.38-23.15), initiate scale (PRR=6.32,
      95% CI=2.51-15.95), monitor scale (PRR=8.11, 95% CI=2.0-32.86), and behavior
      regulation index (PRR=4.09, 95% CI=1.05-15.98). CONCLUSION: In general, the
      results showed that adolescents with atypical antipsychotic treated-schizophrenia
      had higher BRIEF T-score compared, and comparable with their normal group
      control.

PMID- 25598825
TI  - Effects of Add-on Ramelteon on Cognitive Impairment in Patients with
      Schizophrenia: An Open-label Pilot Trial.
AB  - OBJECTIVE: This open-label study examined the effects of ramelteon on cognitive
      functions in 10 outpatients with schizophrenia. METHODS: Ramelteon (8 mg/day) was
      administered to 10 patients with schizophrenia for six months. The verbal fluency
      test, Trail-Making Test, the Wisconsin Card Sorting Test, the Stroop Test, the
      Digit Span Distraction Test, Iowa Gambling Task, the Rey Auditory Verbal Learning
      Test were evaluated at baseline and 6 months after treatment with ramelteon.
      RESULTS: Ramelteon improved significantly the scores of Rey Auditory Verbal
      Learning Test. Additionally, ramelteon exerted improvements in the verbal fluency
      and Iowa Gambling Task in 4 patients. CONCLUSION: Ramelteon could be a potential
      therapeutic drug, in adjunctive treatment of learning and memory deficits seen in
      patients with schizophrenia.

PMID- 25598824
TI  - Regulation of interleukin-6 and leptin in schizophrenia patients: a preliminary
      analysis.
AB  - OBJECTIVE: Immune-inflammatory mediators play a pivotal role in brain signaling
      and have been increasingly associated with the pathophysiology of schizophrenia.
      Many studies have indicated an increased level of immune-inflammatory interleukin
      6 (IL-6) in schizophrenia. IL-6 is a well-known chief stimulator of inflammation.
      Of late leptin has also been implicated in the inflammatory pathway of
      schizophrenia. In this study we measured and compared serum levels of IL-6 and
      leptin in patients with schizophrenia to healthy controls, and investigated the
      relationship between IL-6 and leptin. METHODS: Serum IL-6 and leptin were
      determined in 20 patients diagnosed with schizophrenia and in 19 healthy controls
      matched by gender, age and body mass index (BMI) using commercial Bioplex assays.
      RESULTS: Using Mann-Whitney U-test, significantly increased IL-6 levels were
      found in the patients but there was no significant difference in leptin levels
      though a trend towards higher leptin was observed in the patients. Spearman
      correlations did not show any correlation between IL-6 and clinical variables
      except antipsychotic dosage. Leptin significantly correlated with gender and BMI.
      A large effect size correlation was observed between IL-6 and leptin in the
      patients but not in the controls. Multiple regression analysis performed on
      patients, after adjusting for gender and BMI, revealed there was no significant
      association between IL-6 and leptin. CONCLUSION: IL-6 and leptin levels may
      reflect the chronic inflammatory state associated with schizophrenia but further
      evaluation is required. Also, it is important to consider the confounding effects
      of obesity in any examination of relationships between groups with regard to
      cytokines and adipokines.

PMID- 25598826
TI  - Two-channel Near-infrared Spectroscopic Analysis of Association of Paranoia
      Symptoms with Prefrontal Activation.
AB  - OBJECTIVE: The relationship between paranoia symptoms and underlying prefrontal
      cortex mechanisms among healthy subjects was analyzed using near-infrared
      spectroscopy. METHODS: Seventy-eight healthy subjects were assessed for paranoia
      symptoms using the Japanese version of the Paranoia Checklist. Changes in
      hemoglobin concentrations were assessed using 2-channel near-infrared
      spectroscopy on the surface of the prefrontal cortex while subjects performed a
      verbal fluency test. RESULTS: Changes in the concentration of oxygenated
      hemoglobin in the prefrontal cortex during a verbal fluency test did not
      correlate with the Japanese version of the Paranoia Checklist. CONCLUSION: Our
      findings show that the symptoms of paranoia do not negatively affect the
      prefrontal cortex function among healthy subjects.

PMID- 25598827
TI  - Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory
      Hallucinations in Patients with Schizophrenia: A Randomized Controlled, Cross
      over Study.
AB  - OBJECTIVE: A randomized double-blind cross-over trial was conducted in patients
      with persistent auditory hallucinations (AHs) to investigate whether bilateral
      repetitive transcranial magnetic stimulation (rTMS) at the temporoparietal area
      or Broca's area is more effective at high- or low-frequencies compared to a sham
      condition. METHODS: Twenty three patients with persistent AHs who remained stable
      on the same medication for 2 months were enrolled. They were randomized to one of
      four conditions: low-frequency (1 Hz)-rTMS to the temporoparietal area (L-TP),
      high-frequency (20 Hz)-rTMS to the temporoparietal area (H-TP), high-frequency
      (20 Hz)-rTMS to Broca's area (H-B), or sham. RESULTS: All the four rTMS
      conditions resulted in significant decrease in the scores under the auditory
      hallucination rating scale and hallucination change scale over time. However,
      there were no significant treatment effects or interaction between time and
      treatment, suggesting no superior effects of the new paradigms over the sham
      condition. CONCLUSION: Our findings suggest that bilateral rTMS at the
      temporoparietal area or Broca's area with high- or low-frequency does not produce
      superior effects in reducing AHs compared to sham stimulation.

PMID- 25598828
TI  - No Effect on Body Dissatisfaction of an Interaction between 5-HTTLPR Genotype and
      Neuroticism in a Young Adult Korean Population.
AB  - OBJECTIVE: Many studies suggest an association between the serotonin transporter
      gene-linked polymorphic region (5-HTTLPR) and anxiety-related personality traits
      (e.g., neuroticism) in healthy subjects. This study investigated the interaction
      of 5-HTTLPR genotype on body dissatisfaction by neuroticism and to evaluate the
      interaction of 5-HTTLPR genotype on self-esteem by body dissatisfaction in a
      young adult Korean population. METHODS: Two hundred and eighty three subjects
      were included in this study. The Eysenck Personality Questionnaire-Korean version
      was used to evaluate neuroticism, the Body Dysmorphic Disorder Examination-Self
      Report (BDDE-SR)-Korean version was used to evaluate body dissatisfaction, and
      the Self-Esteem Scale (SES)-Korean version was used to evaluate self-esteem. The
      5-HTTLPR genotype by neuroticism (high : low) interaction was assessed according
      to the total BDDE-SR score, and 5-HTTLPR genotype by BDDE-SR (high : low)
      interaction was assessed according to the total SES score. RESULTS: The analysis
      of 5-HTTLPR genotype and neuroticism (high : low) with respect to body
      dissatisfaction showed no main effects of genotype whereas neuroticism did
      influence the BDDE-SR score and no interaction of the genotype with neuroticism.
      The analysis of 5-HTTLPR genotype and BDDE-SR (high : low) with respect to self
      esteem score showed no main effects of genotype whereas BDDE-SR did influence the
      self-esteem score and no interaction of the genotype with body dissatisfaction.
      CONCLUSION: These results suggest that an interaction between 5-HTTPLR genotype
      and neuroticism does not affect body dissatisfaction and an interaction between 5
      HTTPLR genotype and body dissatisfaction does not affect self-esteem in a young
      adult Korean population.

PMID- 25598830
TI  - Post-traumatic Stress Disorder Symptoms in a Female Patient Following Repeated
      Teasing: Treatment with Gabapentin and Lamotrigine and the Possible Role of
      Sensitization.
AB  - Post-traumatic stress disorder (PTSD) is a pathological response to trauma
      characterized by frequent recollections, recurrent nightmares, and flashbacks of
      the traumatic event(s). To date, the precise mechanisms underlying the
      development of PTSD remain unknown. Several studies have suggested that
      antiepileptic drugs, such as gabapentin and lamotrigine, may be effective in the
      treatment of PTSD symptoms. We report on a 15-year-old Japanese female junior
      high school student who developed PTSD symptoms following repeated teasing from
      male classmates. Additionally, we underscore the beneficial effects of treatment
      with gabapentin and lamotrigine on flashbacks and nightmares. This patient
      developed PTSD symptoms after repeated teasing from male classmates at school.
      Her flashbacks and nightmares were treated with a combination of gabapentin and
      lamotrigine. After recovery, treatment with lamotrigine alone controlled her
      symptoms. Our observations suggest that a process of sensitization may be
      involved in the development of PTSD symptoms. Additionally, gabapentin and/or
      lamotrigine were effective in the treatment of flashbacks and nightmares in this
      patient. Thus, doctors should consider using these anti-epileptic drugs as an
      alternative approach to treating PTSD symptoms. 

PMID- 25598829
TI  - Adolescent with tourette syndrome and bipolar disorder: a case report.
AB  - Tourette syndrome consists of multiple motor tics and one or more vocal tics.
      Psychopathology occurs in approximately 90% of Tourette syndrome patients, with
      attention-deficit/hyperactivity, mood, and obsessive-compulsive disorders being
      common. Additionally, Tourette syndrome and bipolar disorder may be related in
      some individuals. However, it is unclear why bipolar disorder may be
      overrepresented in Tourette syndrome patients, and more research is needed.
      Herein, we report the case of a 15-year-old boy diagnosed with both Tourette
      syndrome and bipolar disorder, whose symptoms improved with aripiprazole,
      atomoxetine, and valproate. The patient was diagnosed with Tourette syndrome at 8
      years of age when he developed tics and experienced his first depressive episode.
      The patient had a poor response to a variety of antidepressants and anti-tic
      medications. A combination of valproate and aripiprazole stabilized both the
      patient's tics and mood symptoms. It is important to assess individuals with
      Tourette syndrome for other disorders, including bipolar disorder. The treatment
      of children and adolescents with both Tourette syndrome and bipolar disorder is
      an important clinical issue. 

PMID- 25598832
TI  - The cost of biologics for psoriasis is increasing.
AB  - BACKGROUND: Biologic agents have revolutionized the management of psoriasis but
      at a higher cost compared with "traditional" agents. Cost must be considered when
      evaluating management options for psoriasis. OBJECTIVE: To estimate the annual
      cost of treatment of psoriasis using biologic agents and assess the trend over
      the past decade. METHODS: The cost of annual treatment paradigms for etanercept,
      adalimumab, and ustekinumab was estimated using the average wholesale price.
      Trends were assessed by calculating the percentage change in annual cost compared
      with the previous year. A sales-based cost of drugs was estimated using gross US
      sales of each drug and an estimate of the total number of patients treated based
      on prescription data. RESULTS: The cost of one year of induction and maintenance
      treatment was highest for ustekinumab ($53,909), followed by etanercept
      ($46,395), and adalimumab ($39,041). The sales-based cost of drugs was greatest
      for ustekinumab ($25,012), then adalimumab ($6,786) and etanercept ($6,629).
      Sales-based cost increased at an average of 20% per year. CONCLUSION: The cost of
      biologic treatments for psoriasis has been increasing. Cost considerations in the
      management of psoriasis are likely to increase given the limited healthcare
      resources that are available.

PMID- 25598831
TI  - Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of
      antidiabetic agents.
AB  - Although several treatment options are available to reduce hyperglycemia, only
      about half of individuals with diagnosed diabetes mellitus (DM) achieve
      recommended glycemic targets. New agents that reduce blood glucose concentrations
      by novel mechanisms and have acceptable safety profiles are needed to improve
      glycemic control and reduce the complications associated with type 2 diabetes
      mellitus (T2DM). The renal sodium-glucose co-transporter 2 (SGLT2) is responsible
      for reabsorption of most of the glucose filtered by the kidney. Inhibitors of
      SGLT2 lower blood glucose independent of the secretion and action of insulin by
      inhibiting renal reabsorption of glucose, thereby promoting the increased urinary
      excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are
      SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe,
      and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase
      renal excretion of glucose and improve glycemic parameters in patients with T2DM
      when used as monotherapy or in combination with other antihyperglycemic agents.
      Treatment with SGLT2 inhibitors is associated with weight reduction, lowered
      blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall,
      canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of
      genital infections and, in some studies, urinary tract infections have been more
      frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients
      compared with those receiving placebo. Evidence from clinical trials suggests
      that SGLT2 inhibitors are a promising new treatment option for T2DM. 

PMID- 25598833
TI  - Hypertension in adult Fabry's disease: is cardiotrophin-1 a diagnostic biomarker?
AB  - BACKGROUND: Cardiotrophin-1 (CT-1), a cytokine produced by cardiomyocytes and non
      cardiomyocytes in conditions of stress, can be used as a biomarker of left
      ventricular hypertrophy and dysfunction in hypertensive patients. Hypertension is
      one of the main adverse events in the third and last phase of Fabry's disease
      (FD). We measured CT-1 in order to examine its correlation with the vascular and
      cardiac alterations at different ages and assess its potential for use as a
      biomarker of hypertension in FD. FINDINGS: The level of CT-1 was clearly higher
      in hypertensive adults than in adult FD patients. FD patients show a small, non
      significant decrease in plasma CT-1 with age, while in hypertensive patients CT-1
      in plasma rises strongly and highly significantly with age. CONCLUSIONS: CT-1 can
      be considered a good biomarker of the progression of hypertension with age, but
      particular care is needed when following hypertension in FD patients, since CT-1
      does not correlate the same way with this disease.

PMID- 25598834
TI  - Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and
      MAI infection: some new conflicting data.
AB  - BACKGROUND: While HIV, AIDS and atypical Mycobacterium infections are closely
      linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based
      regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in
      situation of rifampicin co-medication, because RAL is more rapidly metabolized
      due to rifampicin-induced Uridine-5'-diphosph- gluronosyl-transferase (UGT1A1).
      Recently, it was speculated that chewed RAL might lead to increased absorption,
      which might compensate the inductive effect of rifampicin-rapid metabolized RAL,
      as part of cost-saving effects in countries with high-tuberculosis prevalence and
      less economic power. METHODS: We report measurement of raltegravir
      pharmacokinetics in a 34-year AIDS-patient suffering from disseminated
      Mycobacterium avium infection with necessity of parenteral rifampicin treatment.
      RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11
      ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical
      analysis, a two-sided Wilcoxon signed rank test for paired samples was used.
      RESULTS: High intra-personal variability in raltegravir serum levels was seen.
      Comparable Cmax concentrations were found for 800 mg chewed and swallowed RAL, as
      well as for 400 mg chewed and swallowed RAL. While Cmax seems to be more
      dependent from overall RAL dosing than from swallowed or chewed tablets,
      increased AUC12 is clearly linked to higher RAL dosages per administration.
      Anyway, chewed raltegravir showed a rapid decrease in serum levels. CONCLUSIONS:
      We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co
      medication leads to optimized pharmacokinetics. There is need for more data from
      randomized trials for further recommendations.

PMID- 25598835
TI  - HIV Encephalopathy: pediatric case series description and insights from the
      clinic coalface.
AB  - BACKGROUND: The Human Immune Deficiency Virus (HIV) can manifest neurologically
      in both adults and children. Early invasion of the central nervous system by the
      virus, affecting the developing brain, is believed to result in the most common
      primary HIV-related neurological complication, HIV Encephalopathy (HIVE). In
      countries such as South Africa where many children have not been initiated on
      antiretroviral treatment early, HIVE remains a significant clinical problem.
      METHODS: Children were selected from a clinic for children with neurologic
      complications of HIV, located at the Red Cross War Memorial Children's Hospital,
      South Africa 2008-2012. Eligible subjects fulfilled the following inclusion
      criteria: aged 6 months-13 years; positive diagnosis of HIV infection, vertically
      infected and HIVE as defined by CDC criteria. Each participant was prospectively
      assessed by a Pediatric Neurologist using a standardized proforma which collated
      relevant details of background, clinical and immunological status. RESULTS: The
      median age of the 87 children was 64 months (interquartile range 27-95 months).
      All except one child were on antiretroviral treatment, 45% had commenced
      treatment <12 months of age. Delayed early motor milestones were reported in 80%
      and delayed early speech in 75% of children in whom we had the information.
      Twenty percent had a history of one or more seizures and 41% had a history of
      behavior problems. Forty-eight percent had microcephaly and 63% a spastic
      diplegia. CD4 percentages followed a normal distribution with mean of 30.3% (SD
      8.69). Viral loads were undetectable (<log 1.6) in 70% of the children. Brain
      imaging was performed on 56% with 71% of those imaged demonstrating at least one
      abnormality, most commonly white matter volume loss or signal abnormality.
      CONCLUSIONS: Amongst the cohort of children referred to this clinic, the
      diagnosis of HIVE was unrecognized in the general medical services, even in its
      most severe form. Developmental delay and school failure were major presenting
      problems. Co-morbidities are a frequent finding and should be sought actively in
      order to optimize management and promote best possible outcomes for this
      vulnerable group of children.

PMID- 25598836
TI  - Arsenic exposure is associated with DNA hypermethylation of the tumor suppressor
      gene p16.
AB  - BACKGROUND: Occupational and environmental exposure to inorganic arsenic leads to
      development of cancer and represents a significant health hazard in more than 70
      countries. The underlying mechanism for arsenic-induced carcinogenesis remains
      unclear. Laboratory studies suggest that arsenic is a poor mutagen but may cause
      epigenetic silencing of key tumor suppressor genes such as p16 through DNA
      hypermethylation. However, the evidence for an association between human arsenic
      exposure and abnormal DNA methylation of tumor suppressor genes is lacking.
      FINDINGS: Paired case-control studies were conducted involving 40 individuals
      with high arsenic exposure and arsenicosis, 40 individuals with similarly high
      exposure to arsenic but without arsenicosis, and 40 individuals with normal
      exposure to arsenic. DNA methylation status of p16 was determined using
      methylation-specific PCR. Conditional logistic regression analysis showed that
      DNA hypermethylation of p16 gene was significantly associated with high arsenic
      exposure (Odds Ratio = 10.0, P = 0.0019) independently of the development of
      arsenicosis (Odds Ratio = 2.0, P = 0.1343). CONCLUSIONS: High exposure of arsenic
      in human is positively linked to DNA hypermethylation of p16 gene, suggesting
      that epigenetic silencing of key tumor suppressor may be an important mechanism
      by which arsenic promotes cancer initiation.

PMID- 25598838
TI  - Retrospective study of the effectiveness of Intra-Aortic Balloon Occlusion (IABO)
      for traumatic haemorrhagic shock.
AB  - INTRODUCTION: Intra-aortic balloon occlusion (IABO) is useful for proximal
      vascular control, by clamping the descending aorta, in traumatic haemorrhagic
      shock. However, there are limited clinical studies regarding its effectiveness.
      This study aimed at investigating the effectiveness of IABO for traumatic
      haemorrhagic shock. METHODS: This retrospective, observational study included
      trauma patients who underwent IABO at the Emergency and Critical Care Center of
      Nippon Medical School Tama-Nagayama Hospital between January 2009 and March 2013.
      14 patients were included to this study who were in shock on arrival (systolic
      blood pressure [SBP] <90 mmHg or shock index >=1), underwent IABO for
      resuscitation and temporary haemostasis, and subsequently underwent haemostatic
      intervention (operation or transcatheter arterial embolization). Patient
      characteristics, physiological status, SBP, heart rate (HR), initial fluid and
      blood transfusion, time course, and total occlusion time were compared before and
      after IABO as well as between the survived (n = 5) and non-survived (n = 9)
      groups. RESULTS: The majority of patients experienced blunt injuries, with an
      average injury severity score of 29.5. The liver, pelvis, spleen, and mesenterium
      represented the majority of injured organs. SBP, but not HR, was significantly
      higher after IABO than before IABO (123.1 vs. 65.5 mmHg, P = 0.0001). The revised
      trauma score and probability of survival were significantly different between the
      survived and non-survived groups (both, P = 0.04). The survived group required
      significantly less blood transfusion volume than the non-survived group (20 vs.
      33.7 red blood cell units, P = 0.04). In addition, the survived group required a
      significantly shorter total occlusion time than the non-survived group (46.2 vs.
      224.1 min, P = 0.002). CONCLUSIONS: IABO was used for relatively severe trauma
      patients. SBP was significantly higher after IABO, but was not related to
      survival. However, blood transfusion volume and total occlusion time were related
      to survival; therefore, it is important to reduce or shorten these parameters,
      i.e., immediate definitive haemostasis. IABO is effective for traumatic
      haemorrhagic shock; however, it is also important to consider these points and
      potential complications.

PMID- 25598839
TI  - Social network analysis of international scientific collaboration on psychiatry
      research.
AB  - BACKGROUND: Mental disorder is harmful to human health, effects social life
      seriously and still brings a heavy burden for countries all over the world.
      Scientific collaboration has become the indispensable choice for progress in the
      field of biomedicine. However, there have been few scientific publications on
      scientific collaboration in psychiatry research so far. The aim of this study was
      to measure the activities of scientific collaboration in psychiatry research at
      the level of authors, institutions and countries. METHODS: We retrieved 36557
      papers about psychiatry from Science Ciation Index Expanded (SCI-Expanded) in web
      of science. Additionally, some methods such as social network analysis (SNA), K
      plex analysis and Core-Periphery were used in this study. RESULTS: Collaboration
      has been increasing at the level of authors, institutions and countries in
      psychiatry in the last ten years. We selected the top 100 prolific authors,
      institutions and 30 countries to construct collaborative map respectively.
      Freedman, R and Seidman, LJ were the central authors, Harvard university was the
      central institution and the USA was the central country of the whole network.
      Notably, the rate of economic development of countries affected collaborative
      behavior. CONCLUSION: The results show that we should encourage multiple
      collaboration types in psychiatry research as they not only help researchers to
      master the current research hotspots but also provide scientific basis for
      clinical research on psychiatry and suggest policies to promote the development
      of this area.

PMID- 25598840
TI  - Direct and up-close views of plant cell walls show a leading role for lignin
      modifying enzymes on ensuing xylanases.
AB  - BACKGROUND: A key barrier that limits the full potential of biological processes
      to create new, sustainable materials and fuels from plant fibre is limited enzyme
      accessibility to polysaccharides and lignin that characterize lignocellulose
      networks. Moreover, the heterogeneity of lignocellulosic substrates means that
      different enzyme combinations might be required for efficient transformation of
      different plant resources. Analytical techniques with high chemical sensitivity
      and spatial resolution that permit direct characterization of solid samples could
      help overcome these challenges by allowing direct visualization of enzyme action
      within plant fibre, thereby identify barriers to enzyme action. RESULTS: In the
      current study, the high spatial resolution (about 30 nm) of scanning transmission
      X-ray microscopy (STXM), and the detection sensitivity (ppm) of time-of-flight
      secondary ion mass spectrometry (ToF-SIMS), were harnessed for the first time to
      investigate the progression of laccase, cellulase and xylanase activities through
      wood samples, and to evaluate complementary action between lignin-modifying and
      polysaccharide-degrading enzymes. In particular, complementary insights from the
      STXM and ToF-SIMS analyses revealed the key role of laccase in promoting xylanase
      activity throughout and between plant cell walls. CONCLUSIONS: The spatial
      resolution of STXM clearly revealed time-dependent progression and spatial
      distribution of laccase and xylanase activities, whereas ToF-SIMS analyses
      confirmed that laccase promoted protein penetration into fibre samples, leading
      to an overall increase in polysaccharide degradation. Spectromicroscopic
      visualizations of plant cell wall chemistry allowed simultaneous tracking of
      changes to lignin and polysaccharide contents, which provides new possibilities
      for investigating the complementary roles of lignin-modifying and carbohydrate
      active enzymes.

PMID- 25598841
TI  - Developing an in vitro screening assay platform for evaluation of antifibrotic
      drugs using precision-cut liver slices.
AB  - BACKGROUND: Precision-cut liver slices present different cell types of liver in a
      physiological context, and they have been explored as effective in vitro model
      systems to study liver fibrosis. Inducing fibrosis in the liver slices using
      toxicants like carbon tetrachloride is of less relevance to human disease
      conditions. Our aim for this study was to establish physiologically relevant
      conditions in vitro to induce fibrotic phenotypes in the liver slices. RESULTS:
      Precision-cut liver slices of 150 MUm thickness were obtained from female C57BL/6
      J mice. The slices were cultured for 24 hours in media containing a cocktail of
      10 nM each of TGF-beta, PDGF, 5 MUM each of lysophosphatidic acid and sphingosine
      1 phosphate and 0.2 MUg/ml of lipopolysaccharide along with 500 MUM of palmitate
      and were analyzed for triglyceride accumulation, stress and inflammation,
      myofibroblast activation and extracellular matrix (ECM) accumulation. Incubation
      with the cocktail resulted in increased triglyceride accumulation, a hallmark of
      steatosis. The levels of Acta2, a hallmark of myofibroblast activation and the
      levels of inflammatory genes (IL-6, TNF-alpha and C-reactive protein) were
      significantly elevated. In addition, this treatment resulted in increased levels
      of ECM markers - collagen, lumican and fibronectin. CONCLUSIONS: This study
      reports the experimental conditions required to induce fibrosis associated with
      steatohepatitis using physiologically relevant inducers. The system presented
      here captures various aspects of the fibrosis process like steatosis,
      inflammation, stellate cell activation and ECM accumulation and serves as a
      platform to study the liver fibrosis in vitro and to screen small molecules for
      their antifibrotic activity.

PMID- 25598842
TI  - Genome-wide analysis of H3.3 dissociation reveals high nucleosome turnover at
      distal regulatory regions of embryonic stem cells.
AB  - BACKGROUND: The histone variant H3.3 plays a critical role in maintaining the
      pluripotency of embryonic stem cells (ESCs) by regulating gene expression
      programs important for lineage specification. H3.3 is deposited by various
      chaperones at regulatory sites, gene bodies, and certain heterochromatic sites
      such as telomeres and centromeres. Using Tet-inhibited expression of epitope
      tagged H3.3 combined with ChIP-Seq we undertook genome-wide measurements of H3.3
      dissociation rates across the ESC genome and examined the relationship between
      H3.3-nucleosome turnover and ESC-specific transcription factors, chromatin
      modifiers, and epigenetic marks. RESULTS: Our comprehensive analysis of H3.3
      dissociation rates revealed distinct H3.3 dissociation dynamics at various
      functional chromatin domains. At transcription start sites, H3.3 dissociates
      rapidly with the highest rate at nucleosome-depleted regions (NDRs) just upstream
      of Pol II binding, followed by low H3.3 dissociation rates across gene bodies.
      H3.3 turnover at transcription start sites, gene bodies, and transcription end
      sites was positively correlated with transcriptional activity. H3.3 is found
      decorated with various histone modifications that regulate transcription and
      maintain chromatin integrity. We find greatly varying H3.3 dissociation rates
      across various histone modification domains: high dissociation rates at active
      histone marks and low dissociation rates at heterochromatic marks. Well- defined
      zones of high H3.3-nucleosome turnover were detected at binding sites of ESC
      specific pluripotency factors and chromatin remodelers, suggesting an important
      role for H3.3 in facilitating protein binding. Among transcription factor binding
      sites we detected higher H3.3 turnover at distal cis-acting sites compared to
      proximal genic transcription factor binding sites. Our results imply that fast
      H3.3 dissociation is a hallmark of interactions between DNA and transcriptional
      regulators. CONCLUSION: Our study demonstrates that H3.3 turnover and nucleosome
      stability vary greatly across the chromatin landscape of embryonic stem cells.
      The presence of high H3.3 turnover at RNA Pol II binding sites at extragenic
      regions as well as at transcription start and end sites of genes, suggests a
      specific role for H3.3 in transcriptional initiation and termination. On the
      other hand, the presence of well-defined zones of high H3.3 dissociation at
      transcription factor and chromatin remodeler binding sites point to a broader
      role in facilitating accessibility.

PMID- 25598837
TI  - Targeting Neovascularization in Ischemic Retinopathy: Recent Advances.
AB  - Pathological retinal neovascularization (RNV) is a common micro-vascular
      complication in several retinal diseases including retinopathy of prematurity,
      diabetic retinopathy, age-related macular degeneration and central vein
      occlusion. The current therapeutic modalities of RNV are invasive and although
      they may slow or halt the progression of the disease they are unlikely to restore
      normal acuity. Therefore, there is an urgent need to develop treatment
      modalities, which are less invasive and therefore associated with fewer
      procedural complications and systemic side effects. This review article
      summarizes our understanding of the pathophysiology and current treatment of RNV
      in ischemic retinopathies; lists potential therapeutic targets; and provides a
      framework for the development of future treatment modalities.

PMID- 25598843
TI  - Dynamic foot function as a risk factor for lower limb overuse injury: a
      systematic review.
AB  - BACKGROUND: Dynamic foot function is considered a risk factor for lower limb
      overuse injuries including Achilles tendinopathy, shin pain, patellofemoral pain
      and stress fractures. However, no single source has systematically appraised and
      summarised the literature to evaluate this proposed relationship. The aim of this
      systematic review was to investigate dynamic foot function as a risk factor for
      lower limb overuse injury. METHODS: A systematic search was performed using
      Medline, CINAHL, Embase and SportDiscus in April 2014 to identify prospective
      cohort studies that utilised dynamic methods of foot assessment. Included studies
      underwent methodological quality appraisal by two independent reviewers using an
      adapted version of the Epidemiological Appraisal Instrument (EAI). Effects were
      expressed as standardised mean differences (SMD) for continuous scaled data, and
      risk ratios (RR) for nominal scaled data. RESULTS: Twelve studies were included
      (total n = 3,773; EAI 0.44 to 1.20 out of 2.00, representing low to moderate
      quality). There was limited to very limited evidence for forefoot, midfoot and
      rearfoot plantar loading variables (SMD 0.47 to 0.85) and rearfoot kinematic
      variables (RR 2.67 to 3.43) as risk factors for patellofemoral pain; and plantar
      loading variables (forefoot, midfoot, rearfoot) as risk factors for Achilles
      tendinopathy (SMD 0.81 to 1.08). While there were significant findings from
      individual studies for plantar loading variables (SMD 0.3 to 0.84) and rearfoot
      kinematic variables (SMD 0.29 to 0.62) as risk factors for 'non-specific lower
      limb overuse injuries', these were often conflicting regarding different
      anatomical regions of the foot. Findings from three studies indicated no evidence
      that dynamic foot function is a risk factor for iliotibial band syndrome or lower
      limb stress fractures. CONCLUSION: This systematic review identified very limited
      evidence that dynamic foot function during walking and running is a risk factor
      for patellofemoral pain, Achilles tendinopathy, and non-specific lower limb
      overuse injuries. It is unclear whether these risk factors can be identified
      clinically (without sophisticated equipment), or modified to prevent or manage
      these injuries. Future prospective cohort studies should address methodological
      limitations, avoid grouping different lower limb overuse injuries, and explore
      clinically meaningful representations of dynamic foot function.

PMID- 25598844
TI  - The role of radiotherapy-resistant stem cells in breast cancer recurrence.

PMID- 25598846
TI  - Challenges and strategies for identifying biomarkers for colorectal cancer.

PMID- 25598845
TI  - Resistance to HER2-targeted therapies: a potential role for FOXM1.
AB  - Despite the tremendous efficacy of trastuzumab against HER2-overexpressing
      metastatic breast cancers, a significant fraction of women demonstrate
      progressive disease during treatment. Multiple mechanisms have been proposed to
      mediate trastuzumab resistance. In this mini-review, we discuss the evidence
      supporting FOXM1 as a mediator of resistance and potential new therapeutic target
      in trastuzumab-refractory breast cancer. FOXM1 expression is significantly
      elevated in multiple breast cancer data sets. Some studies suggest a direct
      correlation between FOXM1 and HER2 expression levels. In addition, overexpression
      of FOXM1 reduces the sensitivity of HER2-positive breast cancer cells to
      trastuzumab or lapatinib. Conversely, knockdown or pharmacological inhibition of
      FOXM1 rescues resistance to HER2-targeted therapies. Current pre-clinical
      information supports further investigation of the role of FOXM1 in trastuzumab
      resistant breast cancer.

PMID- 25598848
TI  - Longitudinal Dynamic Analyses of Cognition in the Health and Retirement Study
      Panel.

PMID- 25598847
TI  - A droplet digital PCR detection method for rare L1 insertions in tumors.
AB  - BACKGROUND: The active human mobile element, long interspersed element 1 (L1)
      currently populates human genomes in excess of 500,000 copies per haploid genome.
      Through its mobility via a process called target primed reverse transcription
      (TPRT), L1 mobilization has resulted in over 100 de novo cases of human disease
      and has recently been associated with various cancer types. Large advances in
      high-throughput sequencing (HTS) technology have allowed for an increased
      understanding of the role of L1 in human cancer; however, researchers are still
      limited by the ability to validate potentially rare L1 insertion events detected
      by HTS that may occur in only a small fraction of tumor cells. Additionally, HTS
      detection of rare events varies greatly as a function of read depth, and new
      tools for de novo element discovery are needed to fill in gaps created by HTS.
      RESULTS: We have employed droplet digital PCR (ddPCR) to detect rare L1 loci in
      mosaic human genomes. Our assay allows for the detection of L1 insertions as rare
      as one cell in every 10,000. CONCLUSIONS: ddPCR represents a robust method to be
      used alongside HTS techniques for detecting, validating and quantitating rare L1
      insertion events in tumors and other tissues.

PMID- 25598849
TI  - Anticipatory role of high density lipoprotein and endothelial dysfunction: an
      overview.
AB  - High Density Lipoprotein (HDL) has been witnessed to possess a range of different
      functions that contribute to its atheroprotective effects. These functions are:
      the promotion of macrophage cholesterol efflux, reverse cholesterol transport,
      anti-inflammatory, anti-thrombotic, anti-apoptotic, pro-fibrinolytic and anti
      oxidative functions. Paraoxonase 1 (PON1) is an HDL associated enzyme
      esterase/homocysteinethiolactonase that contributes to the anti-oxidant and anti
      atherosclerotic capabilities of HDL. PON1 is directly involved in the
      etiopathogenesis of atherosclerosis through the modulation of nitric oxide (NO)
      bioavailability. The aim of this review is to summarize the role of HDL on
      endothelial homeostasis, and also to describe the recently characterized
      molecular pathways involved. 

PMID- 25598851
TI  - Acetate kinase Activity and Kinetic Properties of the Enzyme in Desulfovibrio
      piger Vib-7 and Desulfomicrobium sp. Rod-9 Intestinal Bacterial Strains.
AB  - Activity of acetate kinase in cell-free extracts and individual fractions and the
      kinetic properties of the enzyme obtained from the Desulfovibrio piger Vib-7 and
      Desulfomicrobium sp. Rod-9 intestinal bacterial strains were presented at the
      first time. The highest activity of the enzyme was measured in the cell-free
      extracts (1.52 +/- 0.163 and 0.46 +/- 0.044 U * mg-1 protein for D. piger Vib-7
      and Desulfomicrobium sp. Rod-9, respectively) compared to other fractions. The
      specific activity of acetate kinase in the extracts of both bacterial strains was
      determined at different temperature and pH. Analysis of the kinetic properties of
      the purified acetate kinase was carried out. The acetate kinase activity, initial
      (instantaneous) reaction rate (V0) and maximum rate of the acetate kinase
      reaction (Vmax) in D. piger Vib-7 and Desulfomicrobium sp. Rod-9 intestinal
      bacterial strains were defined. Michaelis constants (KmAcetyl phosphate and
      KmADP) of the enzyme reaction (2.54 +/- 0.26 and 2.39 +/- 0.24 mM for D. piger
      Vib-7 as well as 2.68 +/- 0.25 and 2.47 +/- 0.27 mM for Desulfomicrobium sp. Rod
      9, respectively) were calculated. The described results of acetate kinase, an
      important enzyme in the process of organic compounds oxidation and dissimilatory
      sulfate reduction would be perspective and useful for clarification of the
      etiological role of these bacteria in the development of inflammatory bowel
      diseases in humans and animals. 

PMID- 25598853
TI  - Osteoarthritis at young age, a diagnostic challenge: a case of stickler syndrome.
AB  - A young woman presents with severe polyarticular osteoarthritis with relevant
      family history potentially suggesting a hereditary disease. Previously, the
      patient's mother had been diagnosed with rheumatoid arthritis and reported to
      have suffered from some locomotor problems. Careful clinical evaluation with an
      extensive personal and familial history pointed towards a diagnosis of Stickler
      syndrome, an autosomal dominant condition with progressive arthro-ophthalmopathy,
      (early osteoarthritis and myopia). Following this timely diagnosis, genetic
      counselling was offered. 

PMID- 25598850
TI  - GLP-1(28-36)amide, a Long Ignored Peptide Revisited.
AB  - Glucagon-like peptide-1 (GLP-1), which has been extensively applied for treating
      type 2 diabetes mellitus (T2DM), is an incretin hormone that regulates glucose
      homeostasis. GLP-1(28-36)amide, a C-terminal nonapeptide (FIAWLVKGRamide) of GLP
      1, is a major product derived from the cleavage of GLP-1 by the neutral
      endopeptidase (NEP). GLP-1(28-36)amide has long been regarded as a metabolically
      inactive byproduct, however, recent findings reveal that GLP-1(28-36)amide plays
      multiple novel roles in ameliorating hepatic metabolism, protecting beta cells,
      improving glucose disposal and inhibiting weight gain. Here, we summarize the
      latest progress on the effects of GLP-1(28-36)amide with a focus on its roles in
      regulating the Wnt and mitochondrial-mediated signaling pathways. 

PMID- 25598852
TI  - Before the vaccines: medical treatments of acute paralysis in the 1916 new york
      epidemic of poliomyelitis.
AB  - Hospitals in New York were overwhelmed by the epidemic. With nothing known about
      the virus, most cases were treated with traditional or symptomatic remedies. New
      treatments were made though unsuccessful. Serum from various sources was given
      although it was many years before this was found to be ineffectual. Lumbar
      puncture was made, sometimes with additions. Although this became standard
      treatment, there were some who thought it was harmful. Many histories of polio
      ignore treatment. 

PMID- 25598854
TI  - Monitoring complete blood counts and haemoglobin levels in osteoarthritis
      patients: results from a European survey investigating primary care physician
      behaviours and understanding.
AB  - BACKGROUND: Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is
      associated with an increased risk of gastrointestinal (GI) toxicity, including
      occult blood loss and the development of clinically significant anaemia. METHODS:
      700 primary care physicians who routinely used NSAIDs to manage their patients
      were questioned to probe their understanding of the potential importance of blood
      loss in the OA populations they commonly treated with NSAIDs in a chronic
      fashion. RESULTS: Approximately 50% of doctors surveyed measured their
      osteoarthritis patients' haemoglobin routinely as part of a complete blood count
      (CBC). The remaining cohort of physicians only considered conducting CBCs if they
      believed there was cause for concern, with the most common reasons cited being
      anaemia/blood loss (90/80% of physicians respectively) or the patient showing
      signs of weakness and fatigue (78% of physicians). When all doctors were queried
      on their understanding of normal range of haemoglobin (Hb) values, as defined by
      the WHO, significant variation in the absolute figures were reported with
      approximately 40% of physicians citing a low end range for normal that would
      actually place the patient below the threshold for anaemia. CONCLUSION: Physician
      practice in relation to carrying out blood tests in OA patients and their
      understanding of the potential significance of specific results obtained, namely
      haemoglobin values, varies substantially across the countries surveyed. As NSAIDs
      form a pivotal part in the chronic treatment of osteoarthritis and are well
      recognised agents that can precipitate blood loss, guidelines may be needed to
      advise physicians as to when monitoring a patient's haemoglobin levels may be
      appropriate.

PMID- 25598856
TI  - Experiences of spirituality and spiritual values in the context of nursing - an
      integrative review.
AB  - Spirituality is often mistakenly equated with religion but is in fact a far
      broader concept. The aim of this integrative review was to describe experiences
      of the positive impact of spirituality and spiritual values in the context of
      nursing. The analysis was guided by Whittemore and Knafl's integrative review
      method. The findings revealed seven themes: 'Being part of a greater wholeness',
      'Togetherness - value based relationships', 'Developing inner strength',
      'Ministering to patients', 'Maintaining one's sense of humanity', 'Viewing life
      as a gift evokes a desire to 'give back'' and 'Achieving closure - life goes on'.
      It is difficult to draw definite conclusions, as spirituality involves many
      perspectives on various levels of awareness. However, spirituality was considered
      more inclusive, fluid and personal. Furthermore, it emerged that spirituality and
      spiritual values in the context of nursing are closely intertwined with the
      concept of caring. 

PMID- 25598857
TI  - Introduction to a Special Issue of Aeolian Research Airborne mineral dust
      contaminants: Impacts on human health and the environment.

PMID- 25598855
TI  - Metabolic factors in diffuse idiopathic skeletal hyperostosis - a review of
      clinical data.
AB  - OBJECTIVES: We aimed to review the literature linking metabolic factors to
      Diffuse Idiopathic Skeletal Hyperostosis (DISH), in order to assess associations
      between growth factors and DISH. METHOD: We identified studies in our personal
      database and PubMed using the following keywords in various combinations:
      "diffuse idiopathic skeletal hyperostosis", "ankylosing hyperostosis",
      "Forestier's disease", "diabetes", "insulin", "obesity", "metabolic", "growth
      factors", "adipokines", "glucose tolerance" and "chondrocytes". RESULTS: We were
      not able to do a systematic review due to variability in methodology of studies.
      We found positive associations between obesity (especially abdominal obesity),
      Type 2 diabetes mellitus, glucose intolerance, hyperinsulinemia and DISH.
      CONCLUSION: Current research indicates that certain metabolic factors associate
      with DISH. More precise studies deriving from these findings on these and other
      newly identified bone-growth factors are needed.

PMID- 25598858
TI  - A NOVEL SPECTRAL METHOD FOR INFERRING GENERAL DIPLOID SELECTION FROM TIME SERIES
      GENETIC DATA.
AB  - The increased availability of time series genetic variation data from
      experimental evolution studies and ancient DNA samples has created new
      opportunities to identify genomic regions under selective pressure and to
      estimate their associated fitness parameters. However, it is a challenging
      problem to compute the likelihood of non-neutral models for the population allele
      frequency dynamics, given the observed temporal DNA data. Here, we develop a
      novel spectral algorithm to analytically and efficiently integrate over all
      possible frequency trajectories between consecutive time points. This advance
      circumvents the limitations of existing methods which require fine-tuning the
      discretization of the population allele frequency space when numerically
      approximating requisite integrals. Furthermore, our method is flexible enough to
      handle general diploid models of selection where the heterozygote and homozygote
      fitness parameters can take any values, while previous methods focused on only a
      few restricted models of selection. We demonstrate the utility of our method on
      simulated data and also apply it to analyze ancient DNA data from genetic loci
      associated with coat coloration in horses. In contrast to previous studies, our
      exploration of the full fitness parameter space reveals that a heterozygote
      advantage form of balancing selection may have been acting on these loci.

PMID- 25598860
TI  - Elasticity of MoS2 Sheets by Mechanical Deformation Observed by in Situ Electron
      Microscopy.
AB  - MoS2 has been the focus of extensive research due to its potential applications.
      More recently, the mechanical properties of MoS2 layers have raised interest due
      to applications in flexible electronics. In this article, we show in situ
      transmission electron microcsopy (TEM) observation of the mechanical response of
      a few layers of MoS2 to an external load. We used a scanning tunneling microscope
      (STM) tip mounted on a TEM stage to induce deformation on nanosheets of MoS2
      containing few layers. The results confirm the outstanding mechanical properties
      on the MoS2. The layers can be bent close to 180 degrees . However, when the tip
      is retrieved the initial structure is recovered. Evidence indicates that there is
      a significant bond reconstruction during the bending with an outstanding
      capability to recover the initial bond structure. The results show that
      flexibility of three layers of MoS2 remains the same as a single layer while
      increasing the bending modulus by 3 orders of magnitude. Our findings are
      consistent with theoretical calculations and confirm the great potential of MoS2
      for applications.

PMID- 25598859
TI  - Metal-Enhanced Fluorescence from Silver Nanowires with High Aspect Ratio on Glass
      Slides for Biosensing Applications.
AB  - High enhancement of fluorescence emission, improved fluorophore photostability,
      and significant reduction of fluorescence lifetimes have been obtained from high
      aspect ratio (>100) silver (Ag) nanowires. These quantities are found to depend
      on the surface loading of Ag nanowires on glass slides, where the enhancement of
      fluorescence emission increases with the density of nanowires. The surface
      loading dependence was attributed to the creation of intense electric fields
      around the network of Ag nanowires and to the coupling of fluorophore excited
      states that takes place efficiently at a distance of 10 nm from the surface of
      nanowires, which was confirmed by theoretical calculations. The enhancement of
      fluorescence emission of fluorescein isothiocyanate (FITC) was assessed by
      fluorescence spectroscopy and fluorescence-lifetime imaging microscopy (FLIM) to
      demonstrate the potential of high aspect ratio Ag nanowires. Fluorescence
      enhancement factors exceeding 14 were observed on Ag nanowires with high loading
      by FLIM. The photostability of FITC was the highest on nanowires with medium
      loading under continuous laser excitation for 10 min because of the significant
      reduction in the fluorescence lifetime of FITC on these surfaces. These results
      clearly demonstrate the potential of Ag nanowires in metal-enhanced fluorescence
      based applications of biosensing on planar surfaces and cellular imaging.

PMID- 25598861
TI  - Identifying and Intervening with Beginning Readers Who Are At-Risk for Dyslexia:
      Advances in Individualized Classroom Instruction.

PMID- 25598864
TI  - A computerized tomography system for transcranial ultrasound imaging.
AB  - Hardware for tomographic imaging presents both challenge and opportunity for
      simplification when compared with traditional pulse-echo imaging systems.
      Specifically, point diffraction tomography does not require simultaneous powering
      of elements, in theory allowing just a single transmit channel and a single
      receive channel to be coupled with a switching or multiplexing network. In our
      ongoing work on transcranial imaging, we have developed a 512-channel system
      designed to transmit and/or receive a high voltage signal from/to arbitrary
      elements of an imaging array. The overall design follows a hierarchy of modules
      including a software interface, microcontroller, pulse generator, pulse
      amplifier, high-voltage power converter, switching mother board, switching
      daughter board, receiver amplifier, analog-to-digital converter, peak detector,
      memory, and USB communication. Two pulse amplifiers are included, each capable of
      producing up to 400Vpp via power MOSFETS. Switching is based around mechanical
      relays that allow passage of 200V, while still achieving switching times of under
      2ms, with an operating frequency ranging from below 100kHz to 10MHz. The system
      is demonstrated through ex vivo human skulls using 1MHz transducers. The overall
      system design is applicable to planned human studies in transcranial image
      acquisition, and may have additional tomographic applications for other materials
      necessitating a high signal output.

PMID- 25598863
TI  - Identification and Characterization of a Putative Chemotaxis Protein, CheY, from
      the Oral Pathogen Campylobacter rectus.
AB  - Campylobacter rectus is an understudied oral bacterium that contributes to
      periodontitis. Processes that contribute to the disease-causing capabilities of
      pathogens, such as chemotaxis, are largely unknown in C. rectus. The aim of this
      study was to better understand C. rectus chemotaxis, by examining the C. rectus
      genome for the presence of a cheY gene. CheY proteins play a part in chemotaxis
      by acting as two-component response regulators. Significantly, CheY proteins from
      several pathogens, including the related species Campylobacter jejuni, have been
      shown to contribute to bacterial virulence. Degenerate PCR, RT-PCR, sequence
      analyses, and structural modeling showed that C. rectus encodes a gene (Cr-CheY)
      which shares significant homology with previously characterized CheY proteins.
      Functional studies of a recombinant form of the protein supports a likely role of
      Cr-CheY in C. rectus chemotaxis. Cr-CheY is the first CheY characterized from the
      oral campylobacters.

PMID- 25598862
TI  - Modulation of the unfolded protein response impedes tumor cell adaptation to
      proteotoxic stress: a PERK for hepatocellular carcinoma therapy.
AB  - BACKGROUND: Functional disturbances of the endoplasmic reticulum (ER) lead to
      activation of the unfolded protein response (UPR), which is involved in the
      consecutive steps of carcinogenesis. In human hepatocellular carcinoma (HCC), the
      UPR is shown to be activated; however, little is known about the UPR kinetics and
      effects of UPR modulation in HCC. METHODS: We sequentially monitored the UPR over
      time in an orthotopic mouse model for HCC and explored the effects of UPR
      modulation on cell viability and proliferation in vitro and in the mouse model.
      RESULTS: The expression of ER-resident chaperones peaked during tumor initiation
      and increased further during tumor progression, predominantly within the nodules.
      A peak in Ire1 signaling was observed during tumor initiation. The Perk pathway
      was activated during tumor progression, and the proapoptotic target Chop was
      upregulated from week 5 and continued to rise, especially in the tumors. The Atf6
      pathway was modestly activated only after tumor initiation. Consistent with the
      UPR activation, electron microscopy demonstrated ER expansion and reorganization
      in HCC cells in vivo. Strikingly, under ER stress or hypoxia, the Perk inhibitor
      and not the Ire1 inhibitor reduced cell viability and proliferation via
      escalating proteotoxic stress in vitro. Notably, the Perk inhibitor significantly
      decreased tumor burden in the mouse model. CONCLUSION: We provide the first
      evaluation of the UPR dynamics in a long-term cancer model and identified a small
      molecule inhibitor of Perk as a promising strategy for HCC therapy.

PMID- 25598865
TI  - Toward a Behavior of Reciprocity.
AB  - It is frequently believed that autism is characterized by a lack of social or
      emotional reciprocity. In this article, I question that assumption by
      demonstrating how many professionals-researchers and clinicians-and likewise many
      parents, have neglected the true meaning of reciprocity. Reciprocity is "a
      relation of mutual dependence or action or influence," or "a mode of exchange in
      which transactions take place between individuals who are symmetrically placed."
      Assumptions by clinicians and researchers suggest that they have forgotten that
      reciprocity needs to be mutual and symmetrical-that reciprocity is a two-way
      street. Research is reviewed to illustrate that when professionals, peers, and
      parents are taught to act reciprocally, autistic children become more responsive.
      In one randomized clinical trial of "reciprocity training" to parents, their
      autistic children's language developed rapidly and their social engagement
      increased markedly. Other demonstrations of how parents and professionals can
      increase their behavior of reciprocity are provided.

PMID- 25598866
TI  - Technological and Organizational Context around Immunization Reporting and
      Interoperability in Minnesota.
AB  - BACKGROUND: Immunization information systems (IIS) operate in an evolving health
      care landscape with technology changes driven by initiatives such as the Centers
      for Medicare and Medicaid Services EHR incentive program, promoting adoption and
      use of electronic health record (EHR) systems, including standards-based public
      health reporting. There is flux in organizational affiliations to support models
      such as accountable care organizations (ACO). These impact institutional
      structure of how reporting of immunizations occurs and the methods adopted.
      OBJECTIVES: To evaluate the technical and organizational characteristics of
      healthcare provider reporting of immunizations to public health in Minnesota and
      to assess the adoption of standardized codes, formats and transport. METHODS:
      Data on organizations and reporting status was obtained from Minnesota IIS
      (Minnesota Immunization Information Connection: MIIC) by collating information
      from existing lists, specialized queries and review of annual reports. EHR
      adoption data of clinics was obtained in collaboration with informatics office
      supporting the Minnesota e-Health Initiative. These data from various sources
      were merged, checked for quality to create a current state assessment of
      immunization reporting and results validated with subject matter experts.
      RESULTS: Standards-based reporting of immunizations to MIIC increased to 708
      sites over the last 3 years. A growth in automated real-time reporting occurred
      in 2013 with 143 new sites adopting the method. Though the uptake of message
      standards (HL7) has increased, the adoption of current version of HL7 and web
      services transport remains low. The EHR landscape is dominated by a single vendor
      (used by 40% of clinics) in the state. There is trend towards centralized
      reporting of immunizations with an organizational unit reporting for many sites
      ranging from 4 to 140 sites. CONCLUSION: High EHR adoption in Minnesota,
      predominance of a vendor in the market, and centralized reporting models present
      opportunities for better interoperability and also adaptation of strategies to
      fit this landscape. It is essential for IIS managers to have a good understanding
      of their constituent landscape for technical assistance and program planning
      purposes.

PMID- 25598867
TI  - Surveillance of human papilloma virus using reference laboratory data for the
      purpose of evaluating vaccine impact.
AB  - Nationwide positivity rates of high-risk human papillomavirus for the United
      States before and since the introduction of a Human Papillomavirus (HPV) vaccine
      in 2006 would provide insight into the population impact of HPV vaccination. Data
      for high-risk HPV testing results from January 1, 2004 to June 1, 2013 at a
      national reference laboratory were retrospectively analyzed to produce 757,761
      patient records of women between the ages of 14 and 59. Generalized linear models
      and finite mixture models were utilized to eliminate sources of bias and
      establish a population undergoing standard gynecological screening. Unadjusted
      positivity rates for high-risk HPV were 27.2% for all age groups combined.
      Highest rates occurred in women aged 14 to 19. While the positivity rates
      decreased for all age groups from 2004 to 2013, the higher age categories showed
      less downward trend following vaccine introduction, and the two age categories 20
      to 24 and 25 to 29 showed a significantly different downward trend between pre-
      and post-vaccine time periods (-0.1% per year to -1.5% per year, and 0.4% per
      year to -1.5% per year, respectively). All other age groups had rates of change
      that became less negative, indicating a slower rate of decline. 

PMID- 25598868
TI  - Cost Comparison Model: Blended eLearning versus traditional training of community
      health workers.
AB  - OBJECTIVES: Another one million community healthcare workers are needed to
      address the growing global population and increasing demand of health care
      services. This paper describes a cost comparison between two training approaches
      to better understand costs implications of training community health workers
      (CHWs) in Sub-Saharan Africa. METHODS: Our team created a prospective model to
      forecast and compare the costs of two training methods as described in the
      Dalburge Report - (1) a traditional didactic training approach ("baseline") and
      (2) a blended eLearning training approach ("blended"). After running the model
      for training 100,000 CHWs, we compared the results and scaled up those results to
      one million CHWs. RESULTS: A substantial difference exists in total costs between
      the baseline and blended training programs. RESULTS indicate that using a blended
      eLearning approach for training community health care workers could provide a
      total cost savings of 42%. Scaling the model to one million CHWs, the blended
      eLearning training approach reduces total costs by 25%. DISCUSSION: The blended
      eLearning savings are a result of decreased classroom time, thereby reducing the
      costs associated with travel, trainers and classroom costs; and using a tablet
      with WiFi plus a feature phone rather than a smartphone with data plan.
      CONCLUSION: The results of this cost analysis indicate significant savings
      through using a blended eLearning approach in comparison to a traditional
      didactic method for CHW training by as much as 67%. These results correspond to
      the Dalberg publication which indicates that using a blended eLearning approach
      is an opportunity for closing the gap in training community health care workers.

PMID- 25598869
TI  - Early-warning health and process indicators for sentinel surveillance in
      Madagascar 2007-2011.
AB  - BACKGROUND: Epidemics pose major threats in resource-poor countries, and
      surveillance tools for their early detection and response are often inadequate.
      In 2007, a sentinel surveillance system was established in Madagascar, with the
      aim of rapidly identifying potential epidemics of febrile or diarrhoeal syndromes
      and issuing alerts. We present the health and process indicators for the five
      years during which this system was constructed, showing the spatiotemporal
      trends, early-warning sign detection capability and process evaluation through
      timely analyses of high-quality data. METHODS: The Malagasy sentinel surveillance
      network is currently based on data for fever and diarrhoeal syndromes collected
      from 34 primary health centres and reported daily via the transmission of short
      messages from mobile telephones. Data are analysed daily at the Institut Pasteur
      de Madagascar to make it possible to issue alerts more rapidly, and integrated
      process indicators (timeliness, data quality) are used to monitor the system.
      RESULTS: From 2007 to 2011, 917,798 visits were reported. Febrile syndromes
      accounted for about 11% of visits annually, but the trends observed differed
      between years and sentinel sites. From 2007 to 2011, 21 epidemic alerts were
      confirmed. However, delays in data transmission were observed (88% transmitted
      within 24 hours in 2008; 67% in 2011) and the percentage of forms transmitted
      each week for validity control decreased from 99.9% in 2007 to 63.5% in 2011.
      CONCLUSION: A sentinel surveillance scheme should take into account both
      epidemiological and process indicators. It must also be governed by the main
      purpose of the surveillance and by local factors, such as the motivation of
      healthcare workers and telecommunication infrastructure. Permanent evaluation
      indicators are required for regular improvement of the system.

PMID- 25598871
TI  - Patterns and correlates of public health informatics capacity among local health
      departments: an empirical typology.
AB  - OBJECTIVE: Little is known about the nationwide patterns in the use of public
      health informatics systems by local health departments (LHDs) and whether LHDs
      tend to possess informatics capacity across a broad range of information
      functionalities or for a narrower range. This study examined patterns and
      correlates of the presence of public health informatics functionalities within
      LHDs through the creation of a typology of LHD informatics capacities. METHODS:
      Data were available for 459 LHDs from the 2013 National Association of County and
      City Health Officials Profile survey. An empirical typology was created through
      cluster analysis of six public health informatics functionalities: immunization
      registry, electronic disease registry, electronic lab reporting, electronic
      health records, health information exchange, and electronic syndromic
      surveillance system. Three-categories of usage emerged (Low, Mid, High). LHD
      financial, workforce, organization, governance, and leadership characteristics,
      and types of services provided were explored across categories. RESULTS: Low
      informatics capacity LHDs had lower levels of use of each informatics
      functionality than high-informatics capacity LHDs. Mid-informatics capacity LHDs
      had usage levels equivalent to high-capacity LHDs for the three most common
      functionalities and equivalent to low-capacity LHDs for the three least common
      functionalities. Informatics capacity was positively associated with service
      provision, especially for population-focused services. CONCLUSION: Informatics
      capacity is clustered within LHDs. Increasing LHD informatics capacity may
      require LHDs with low levels of informatics capacity to expand capacity across a
      range of functionalities, taking into account their narrower service portfolio.
      LHDs with mid-level informatics capacity may need specialized support in
      enhancing capacity for less common technologies.

PMID- 25598872
TI  - Detrimental complications due to improper antithrombotic management in the
      preoperative period: report of two cases.

PMID- 25598874
TI  - Reversal of rocuronium induced neuromuscular blockade using sugammadex in a
      patient with eclampsia treated by magnesium intraoperatively.

PMID- 25598873
TI  - Combined spinal-epidural anesthesia in a mild thrombocytopenic patient with
      antiphospholipid antibody syndrome.

PMID- 25598870
TI  - Systems Epidemiology: What's in a Name?
AB  - Systems biology is an interdisciplinary effort to integrate molecular, cellular,
      tissue, organ, and organism levels of function into computational models that
      facilitate the identification of general principles. Systems medicine adds a
      disease focus. Systems epidemiology adds yet another level consisting of
      antecedents that might contribute to the disease process in populations. In
      etiologic and prevention research, systems-type thinking about multiple levels of
      causation will allow epidemiologists to identify contributors to disease at
      multiple levels as well as their interactions. In public health, systems
      epidemiology will contribute to the improvement of syndromic surveillance
      methods. We encourage the creation of computational simulation models that
      integrate information about disease etiology, pathogenetic data, and the
      expertise of investigators from different disciplines. 

PMID- 25598875
TI  - Inadequate spinal anesthesia in a parturient with Marfan's syndrome due to dural
      ectasia.

PMID- 25598876
TI  - Anesthesia in a child with adrenoleukodystrophy.

PMID- 25598877
TI  - Iatrogenic rupture of undiagnosed blood blister-like aneurysm during aneurysmal
      neck clipping.

PMID- 25598878
TI  - Cannulation of the dorsal radial artery: an underused, yet useful, technique.

PMID- 25598879
TI  - Recurrence of fatal venous air embolism.

PMID- 25598880
TI  - Dislocation of the temporomandibular joint following general anesthesia.

PMID- 25598881
TI  - Hemophagocytic lymphohistiocytosis in adults.

PMID- 25598882
TI  - Quality improvement for reducing intravenous patient-controlled analgesia self
      discontinuation rate.

PMID- 25598883
TI  - Trajectory avoiding kidney and ureter injury for percutaneous lumbar sympathetic
      block.

PMID- 25598884
TI  - The effect of intrathecal curcumin on mechanical allodynia in rats after L5
      spinal nerve ligation.

PMID- 25598885
TI  - Hydromorphone attenuates intercellular adhesion molecule-1 expressions induced by
      lipopolysaccharide on HCT-116 human colon cancer cells.

PMID- 25598886
TI  - Intraoperative very late stent thrombosis in patient undergoing arthroscopic
      shoulder surgery.

PMID- 25598887
TI  - A comparison of desflurane consumption according to fresh gas flow.

PMID- 25598888
TI  - Successful management of a patient with massive vocal fold granuloma with
      transglottal jet ventilation.

PMID- 25598889
TI  - Easy airway management using the i-gelTM supraglottic airway in a patient with
      Treacher Collins syndrome.

PMID- 25598890
TI  - Bilateral vocal cord paralysis following coronary artery bypass surgery.

PMID- 25598891
TI  - A vallecular cyst in a patient with deep neck infection causing difficult airway
      management.

PMID- 25598892
TI  - Air-Q(r)sp-assisted awake fiberoptic bronchoscopic intubation in a patient with
      Ludwig's angina.

PMID- 25598893
TI  - Reversible endotracheal tube obstruction caused by meconium acting as a check
      valve.

PMID- 25598894
TI  - Variant angina associated with myocardial bridging and obstructive sleep apnea
      syndrome after lumbar spine surgery.

PMID- 25598895
TI  - Anesthetic experience for laparoscopic cholecystectomy in a patient with
      myelodysplastic syndrome with trisomy 8 mosaicism syndrome.

PMID- 25598896
TI  - The effect of dexmedetomidine on propofol injection pain.

PMID- 25598897
TI  - Alternating asystole and atrial fibrillation after infusion of propofol and
      remifentanil with target-controlled infusion.

PMID- 25598898
TI  - General anesthesia for a patient with multiple system atrophy.

PMID- 25598899
TI  - Successful anesthesia in a patient with a history of cardiac arrest following
      rocuronium injection.

PMID- 25598900
TI  - Forearm extravasation injury during robot-assisted low anterior resection.

PMID- 25598901
TI  - Anesthetic experience of a patient with severe change on respiratory mechanics in
      the prone position for spinal surgery.

PMID- 25598902
TI  - Pressure controlled vs. volume controlled ventilation during prone position in
      high-level spinal cord injury patients: a preliminary study.

PMID- 25598904
TI  - Accidental intrathecal injection of dopamine hydrochloride resulting in analgesic
      effects.

PMID- 25598903
TI  - Coronary vasospasm caused by local infiltration of epinephrine after spinal
      anesthesia.

PMID- 25598905
TI  - Anesthesia in a young adult with opsoclonus-myoclonus syndrome.

PMID- 25598907
TI  - Incidental finding of an arachnoid cyst in a patient presenting with features of
      postural headache after spinal anesthesia.

PMID- 25598906
TI  - Radiological analysis of the position of epidural catheters in the thoracic
      epidural space.

PMID- 25598908
TI  - Paroxysmal pain during spinal anesthesia.

PMID- 25598909
TI  - Pseudo-Froin's syndrome, xanthochromia with high protein level of cerebrospinal
      fluid.

PMID- 25598910
TI  - Median sacral artery injury during percutaneous mechanical disc decompression
      using Dekompressor(r).

PMID- 25598911
TI  - Celiac plexus block in a patient with upper abdominal pain caused by diabetic
      gastroparesis.

PMID- 25598912
TI  - Successful treatment of pediatric intervertebral disc calcification using
      ultrasound-guided cervical root block.

PMID- 25598913
TI  - Extra cardiac tumor misdiagnosed as a left atrial myxoma.

PMID- 25598914
TI  - Successful management in a pregnant woman with Eisenmenger's syndrome undergoing
      emergency cesarean section under general anesthesia.

PMID- 25598915
TI  - The tip fracture of the Coopdech bronchial blocker during insertion in the
      patient with lung surgery.

PMID- 25598916
TI  - Severe hemodynamic deterioration caused by cardiac herniation during endoscopic
      thoracic sympathicotomy in a patient with previously undiagnosed congenital
      pericardial defect.

PMID- 25598917
TI  - Acute pulmonary edema due to hypoxia during a difficult intubation in a
      rheumatoid arthritis patient.

PMID- 25598918
TI  - The development of tension pneumothorax during mask ventilation under general
      anesthetic induction.

PMID- 25598919
TI  - Anesthesia for flap surgery in a patient with polymyositis.

PMID- 25598920
TI  - A suspected malignant hyperthermia managed without dantrolene sodium.

PMID- 25598921
TI  - Perioperative consideration of general anesthesia for acromegalic patients.

PMID- 25598922
TI  - Anesthetic management of a preterm neonate intracranial aneurysm clipping.

PMID- 25598923
TI  - Successful use of caudal anesthesia and light sevoflurane mask ventilation for
      inguinal hernia repair in an infant with multiple large intrapulmonary cysts.

PMID- 25598924
TI  - Anesthesia in patients with arthrogryposis multiplex congenita: a report of 10
      patients.

PMID- 25598925
TI  - Anesthesiologist's hand hygiene and disinfection of reusable rubber tourniquet
      with alcohol swabs before intravascular cannulation.

PMID- 25598926
TI  - Use of high-frequency oscillatory ventilation with inhaled nitric oxide in
      congenital diaphragmatic hernia, omphalocele, and patent ductus arteriosus.

PMID- 25598927
TI  - Anesthetic experience of a patient with Prune-belly syndrome.

PMID- 25598929
TI  - Midgut volvulus as a complication of intestinal malrotation in a term pregnancy.

PMID- 25598928
TI  - Ultrasonographic measurement of subclavian vein diameter and regression modeling
      in pediatric patients from a single Korean facility.

PMID- 25598930
TI  - A commitment to excellence.

PMID- 25598931
TI  - Scrotal pain: evaluation and management.
AB  - Scrotal pain is a common complaint in a urological practice. Its diagnosis can
      prove challenging in both acute and chronic forms and requires a thorough and
      complete history and physical examination. This article discusses the evaluation
      and management of several entities of scrotal pain, including testicular torsion,
      epididymitis, postvasectomy pain, varicocele, and chronic orchialgia. 

PMID- 25598932
TI  - Metabolic effects of androgen deprivation therapy.
AB  - The therapeutic effects and side effects of androgen deprivation therapy (ADT),
      which is a main treatment method for metastatic prostate cancer, are well known,
      but the metabolic effects have only recently been studied. This review describes
      the effects of ADT on body habitus, insulin resistance, lipid profiles, diabetes,
      metabolic syndrome, and cardiovascular morbidity and mortality. The review was
      done by using KoreaMed and PubMed to search the medical literature related to
      prostate cancer, ADT, body habitus, lipid profile, diabetes, insulin resistance,
      metabolic syndrome, and cardiovascular disease. ADT increases fat mass and
      decreases lean body mass. Fat mostly accumulates in the subcutaneous area. ADT
      increases total cholesterol, triglycerides, and high-density lipoprotein, as well
      as the risk for insulin resistance and diabetes. ADT also increases the risk for
      cardiovascular events, but insufficient evidence is available for a correlation
      with mortality. ADT changes body habitus and lipid profiles and has different
      characteristics than those of classic metabolic syndrome, but it is related to
      insulin resistance and diabetes. ADT increases the risk for cardiovascular
      events. No consistent guidelines have been proposed for treating the metabolic
      effects of ADT, but the generally recommended treatment methods for lowering the
      risk of diabetes and cardiovascular disease should be fully understood.
      Additional studies are necessary. 

PMID- 25598933
TI  - The association of 5-alpha reductase type 2 (SRD5A2) gene polymorphisms with
      prostate cancer in a Korean population.
AB  - PURPOSE: Steroid 5-alpha reductase type 2 (SRD5A2) modifies testosterone to
      dihydrotestosterone (DHT) in the prostate. Single-nucleotide polymorphisms (SNPs)
      of the SRD5A2 gene might affect DHT. We sought to understand the relationship of
      SRD5A2 SNPs to prostate cancer in the Korean population. MATERIALS AND METHODS:
      Twenty-six common SNPs in the SRD5A2 gene were assessed in 272 prostate cancer
      cases and 173 controls. Single-locus analyses were conducted by using conditional
      logistic regression. Additionally, we performed a haplotype analysis for the
      SRD5A2 SNPs tested. RESULTS: Among the 20 SNPs and 4 haplotypes, there were no
      statistically significant results in the prostate cancer patients and the
      controls. In the logistic analysis of SRD5A2 polymorphisms with prostate-specific
      antigen (PSA) criteria, two SNPs (rs508562, rs11675297) and haplotype 1 displayed
      significant results (odds ratio [OR], 1.76; p=0.05; OR, 1.88-2.02; p=0.01-0.04;
      OR, 0.59; p=0.02, respectively). rs508562, rs11675297, rs2208532, and haplotype 1
      (OR, 1.49; p=0.05; OR, 2.02; p=0.05; OR, 2.01; p=0.04; OR, 0.56-0.64, p=0.03
      0.04, respectively) had significant associations with Gleason score. rs508562,
      rs11675297, and haplotype 1 (OR, 1.41-2.34; p=0.004-0.05; OR, 1.74-1.82; p=0.03
      0.05; OR, 0.42-0.67; p=0.0005-0.03, respectively) were significantly associated
      with clinical stage. CONCLUSIONS: We conclude that there was no significant
      association between SRD5A2 SNPs and the risk of prostate cancer in the Korean
      population. However, we found that some SNPs and 1 haplotype influenced PSA
      level, Gleason score, and clinical stage.

PMID- 25598934
TI  - Expression of survivin in squamous cell carcinoma and transitional cell carcinoma
      of the urinary bladder: a comparative immunohistochemical study.
AB  - PURPOSE: To compare the expression of survivin and its association with
      clinicopathological criteria in major types of urinary bladder carcinoma,
      specifically, transitional cell carcinoma with and without squamous
      differentiation and squamous cell carcinoma. MATERIALS AND METHODS:
      Immunohistochemical staining for survivin and Ki67 was performed on paraffin
      embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20
      transitional cell carcinoma with squamous differentiation, and 32 squamous cell
      carcinoma. Expression of survivin in >10% of tumor cells was described as altered
      survivin status. Ki67 staining in >20% of tumor cells was described as a high
      proliferation index. RESULTS: Altered survivin expression was detected in 60/104
      specimens (58%) and was significantly more frequent in transitional cell
      carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell
      carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell
      carcinoma but not in squamous cell carcinoma, altered survivin status was
      associated with higher tumor grade, higher proliferation index, and recurrence.
      In the whole specimens, altered survivin expression was significantly associated
      with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis
      (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin
      was an independent poor prognostic factor for recurrence. CONCLUSIONS: Unlike in
      transitional cell carcinoma, alteration of survivin expression in squamous cell
      carcinoma occurs less frequently and is not associated with features of tumor
      aggression or patient outcome. These findings raise a question: are urinary
      bladder carcinoma patients with squamous cell carcinoma type suitable candidates
      for survivin vaccine? This is an important question to be answered before
      approving the vaccine in management.

PMID- 25598935
TI  - Impact of adjuvant chemotherapy in patients with upper tract urothelial carcinoma
      and lymphovascular invasion after radical nephroureterectomy.
AB  - PURPOSE: To evaluate the impact of adjuvant chemotherapy (AC) in patients with
      upper tract urothelial carcinoma and lymphovascular invasion (LVI) after radical
      nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed the
      clinical records and clinicopatholgic outcomes of patients (n=552) treated with
      RNU between 1986 and 2013. Patients treated with neoadjuvant chemotherapy and
      those for whom LVI status was not recorded were excluded. Patients were divided
      into two groups according to LVI (n=86) or no LVI (n=256). RESULTS: The study
      included 344 patients (240 men and 104 women) with a median of 53.9 months of
      follow-up (range, 1-297 months) after RNU. Tumors were organ confined (T2/N0) in
      211 (61.3%) and tumor grade high in 291 (84.6%). AC was administered in 64
      patients (18.6%). A total of 280 patients (81.4%) were treated with surgery
      alone. Patients with LVI tended to be older (p=0.049), have a higher pT stage
      (pT3/T4, p<0.001), be pN+ (p<0.001), have a high tumor grade (p<0.001), and
      experience recurrence (p<0.001). In the multivariate analysis, LVI was an
      independent prognostic factor for cancer-specific survival and overall survival
      (p=0.002 and p<0.001, respectively). The multivariate analysis demonstrated that
      in the subgroup of patients with LVI, AC was a significant prognostic factor for
      cancer-specific survival and overall survival (hazard ratio, 0.51; p=0.027 and
      hazard ratio, 0.50; p=0.025, respectively). CONCLUSIONS: AC does not seem to
      reduce mortality in patients with advanced upper tract urothelial carcinoma after
      RNU. In the subgroup of patients with LVI, AC had a positive impact on cancer
      specific survival and overall survival. LVI would be helpful for selecting
      patients who are appropriate for AC.

PMID- 25598936
TI  - Standardized analysis of complications after robot-assisted radical cystectomy:
      Korea University Hospital experience.
AB  - PURPOSE: To analyze the complications after robot-assisted radical cystectomy
      (RARC) by use of a standardized reporting methodology by a single surgeon.
      MATERIALS AND METHODS: We prospectively reviewed a maintained institutional
      database of 52 patients who underwent RARC to manage bladder cancer and were
      followed up in 3 months by a single surgeon at Korea University Medical Center
      from 2007 through 2014. All complications within 90 days of surgery were defined
      and categorized into 5 grades according to the Clavien-Dindo classification.
      Logistic regression analysis was used to identify predictors of complications.
      RESULTS: Fifty percent of patients (26 of 52) experienced a complication of any
      grade <90 days after surgery, and 11 patients (21.2%) experienced a major
      complication. Complications were grouped in systems-based categories. Fifty
      complications occurred in 52 patients and hematologic complication (transfusion)
      was the most common (13 of 52). Wound dehiscence, anastomotic leakage, urinary
      tract obstruction, mechanical obstruction, and thromboembolism occurred as major
      complications. Mean estimated blood loss (EBL) was 247 mL and mean total
      operative time was 496 minutes. The mean number of lymph nodes harvested was
      24.6, with 30.5 for extended dissection. EBL (over 300 mL), operative time, and
      method of urinary diversion were significant negative predictors of minor
      complications, whereas EBL (over 300 mL) was a significant negative predictor of
      major complications (p<0.05). CONCLUSIONS: The present results show that the
      complication rate reported by use of a standardized methodology after robotic
      radical cystectomy is still considerable although comparable to that of
      contemporary robot series. EBL, operative time, and diversion methods were
      predictors of complications.

PMID- 25598937
TI  - Can stone density on plain radiography predict the outcome of extracorporeal
      shockwave lithotripsy for ureteral stones?
AB  - PURPOSE: The objective was to determine whether stone density on plain
      radiography (kidney-ureter-bladder, KUB) could predict the outcome of
      extracorporeal shockwave lithotripsy (ESWL) for ureteral stones. MATERIALS AND
      METHODS: A total of 223 patients treated by ESWL for radio-opaque ureteral stones
      of 5 to 20 mm were included in this retrospective study. All patients underwent
      routine blood and urine analyses, plain radiography (KUB), and noncontrast
      computed tomography (NCCT) before ESWL. Demographic, stone, and radiological
      characteristics on KUB and NCCT were analyzed. The patients were categorized into
      two groups: lower-density (LD) group (radiodensity less than or equal to that of
      the 12th rib, n=163) and higher-density (HD) group (radiodensity greater than
      that of the 12th rib, n=60). Stone-free status was assessed by KUB every week
      after ESWL. A successful outcome was defined as stone free within 1 month after
      ESWL. RESULTS: Mean stone size in the LD group was significantly smaller than
      that in the HD group (7.5+/-1.4 mm compared with 9.9+/-2.9 mm, p=0.002). The
      overall success rates in the LD and HD groups were 82.1% and 60.0%, respectively
      (p=0.007). The mean duration of stone-free status and average number of SWL
      sessions required for success in the two groups were 21.7 compared with 39.2 days
      and 1.8 compared with 2.3, respectively (p<0.05). On multivariate logistic
      analysis, stone size and time to ESWL since colic and radiodensity of the stone
      on KUB were independent predictors of successful ESWL. CONCLUSIONS: Our data
      suggest that larger stone size, longer time to ESWL, and ureteral stones with a
      radiodensity greater than that of the 12th rib may be at a relatively higher risk
      of ESWL failure 1 month after the procedure.

PMID- 25598938
TI  - Ureteral stricture formation after ureteroscope treatment of impacted calculi: a
      prospective study.
AB  - PURPOSE: Urinary calculi is a familiar disease. A well-known complication of
      endourological treatment for impacted ureteral stones is the formation of
      ureteral strictures, which has been reported to occur in 14.2% to 24% of cases.
      MATERIALS AND METHODS: This was a prospective study. Ureterotripsy treatment was
      used on patients with impacted ureteral stones. Then, after 3 months and 6
      months, the condition of these patients was assessed by means of a kidney-ureter
      bladder (KUB) ultrasound. If the KUB ultrasound indicated moderate to serious
      hydronephrosis, the patient was further assessed by means of a computed
      tomography intravenous urogram or retrograde pyelogram to confirm the occurrence
      of ureteral strictures. RESULTS: Of the 77 patients who participated in the
      study, 5 developed ureteral strictures. Thus, the stricture rate was 7.8%. An
      analysis of the intraoperative risk factors including perforation of the ureter,
      damage to the mucous membrane, and residual stone impacted within the ureter
      mucosa revealed that none of these factors contributed significantly to the
      formation of the ureteric strictures. The stone-related risk factors that were
      taken into consideration were stone size, stone impaction site, and duration of
      impaction. These stone factors also did not contribute significantly to the
      formation of the ureteral strictures. CONCLUSIONS: This prospective study failed
      to identify any predictable factors for ureteral stricture formation. It is
      proposed that all patients undergo a simple postoperative KUB ultrasound
      screening 3 months after undergoing endoscopic treatment for impacted ureteral
      stones.

PMID- 25598939
TI  - Community-based research on the benign prostatic hyperplasia prevalence rate in
      Korean rural area.
AB  - PURPOSE: We investigated the prevalence rate of benign prostatic hyperplasia
      (BPH) among Korean males in a rural area through a cross-sectional, community
      based epidemiologic survey and analyzed the correlation with epidemiologic
      factors. MATERIALS AND METHODS: A total of 779 males who lived in Yangpyeong
      County participated in a prostate examination campaign. Targeting these men, we
      collected the International Prostate Symptom Score (IPSS), medical history,
      demographic information, serum prostate-specific antigen, and prostate volume as
      measured by transrectal ultrasonography. The data for 599 participants were
      analyzed, excluding 180 men who had a possibility of prostate cancer. BPH was
      defined as an IPSS of 8 points or higher and a prostate volume of 25 mL or more.
      RESULTS: The prevalence rate of BPH was 20.0%. The prevalence rate increased with
      age. There were 2 subjects (4.4%) in the age group of 40-49 years, 18 subjects
      (10.9%) in the age group of 50-59 years, 44 subjects (22%) in the age group of 60
      69 years, and 56 subjects (26.6%) in the age group of over 70 years; this
      increase with age was statistically significant (p<0.001). In the BPH group, the
      average IPSS was 14.67+/-5.95, the average prostate volume was 37.04+/-11.71 g,
      and the average prostate-specific antigen value was 1.56+/-0.88 ng/mL. In the
      analysis of correlations between the epidemiologic factors and the risk of BPH,
      smoking was the only statistically significant factor. CONCLUSIONS: The total
      prevalence rate of BPH in this study was 20.0%, which was a little lower than the
      rate reported in other cities or rural areas.

PMID- 25598940
TI  - Association between renal function, erectile function and coronary artery
      disease: detection with coronary angiography.
AB  - PURPOSE: Many patients admitted for acute myocardial infarction (AMI) have
      chronic renal insufficiency and erectile dysfunction (ED). This study aimed to
      evaluate the relationship between ED and the glomerular filtration rate (GFR) in
      patients with coronary artery disease. MATERIALS AND METHODS: We studied 183
      patients undergoing coronary angiography owing to AMI. The GFR was calculated and
      the International Index of Erectile Function-5 (IIEF-5) was used to evaluate ED.
      The relations between erectile function, GFR, and the number of occluded coronary
      arteries were evaluated. RESULTS: Of 183 patients with a mean age of 55.2+/-11.16
      years who underwent coronary angiography owing to AMI, 100 (54.64%) had ED. The
      ED rate was 45.36% (44/97) in patients with single-vessel disease, 64.5% (31/48)
      in patients with two-vessel disease, and 65.7% (25/38) in patients with three
      vessel disease. The ED rate in patients with single-vessel disease was
      significantly lower than in the other groups (p<0.001). The mean IIEF scores were
      24.2+/-4.3, 20.4+/-4.9, and 20.5+/-4.2 in the three groups, respectively
      (p<0.001). Mean GFRs were similar in patients with single-vessel disease, two
      vessel disease, and three-vessel disease (128.2+/-46.8, 130.8+/-70.9, and 110.8+/
      44.6, respectively, p=0.171). The GFR was significantly lower in the presence of
      ED only for single-vessel disease (p=0.001). CONCLUSIONS: This study confirmed
      that the presence and severity of ED are linked to the number of occluded vessels
      as documented by coronary angiography. The presence of ED and reduced GFR are
      associated with single-vessel coronary artery disease. This relationship can be
      used to predict the likelihood of coronary artery disease.

PMID- 25598941
TI  - Heart failure as the first manifestation of renal cell carcinoma.
AB  - We report the rare case of a patient with advanced renal cell carcinoma (RCC) who
      initially presented to the hospital with symptoms of cardiac failure.
      Preoperative cardiac studies did not reveal any underlying ischemia. After
      resection of a large 14-cm left renal tumor, cardiac function was noted to
      improve dramatically. We discuss this case of concomitant RCC and nonischemic
      cardiomyopathy. 

PMID- 25598942
TI  - A Novel Surgical Pre-suturing Technique for the Management of Ankyloglossia.
AB  - Ankyloglossia or "tongue-tie" is a congenital anomaly caused by tight lingual
      frenulum that abnormally connects the tongue base to the floor of the mouth.
      Ankyloglossia can results in difficulty during speech and deglutition. This case
      series presents a novel surgical technique in the management of ankyloglossia in
      using presuturing technique in which different sets of sutures are given on
      lingual frenum before severing it. This results in reduced opening of the wound,
      minimal bleeding, pain and discomfort. Two male patients with severe
      ankyloglossia had been managed with this technique and after 2 years of follow-up
      of these cases showed satisfactory protrusive and lateral movement of the tongue
      with minimal scarring and discomfort. 

PMID- 25598944
TI  - Retrorectal cystic hamartoma: a problematic 'tail'.
AB  - The retrorectal space is an uncommon seat for neoplastic masses. Retrorectal
      hamartoma or tailgut cyst (TGC) is an uncommon developmental cystic lesion
      occurring in this space which mostly occurs in middle-aged females. We recently
      cared for a 16-year-old girl who presented with vague lower abdominal pain and
      occasional constipation. Per rectal examination revealed an extraluminal mass
      bulging from posterior rectal wall. Preoperative radiological investigations
      revealed by suggested it to be a mature cystic teratoma. The patient underwent
      exploratory laprotomy with en masse excision of the cyst. Histopathological
      examination of the specimen showed it to be a TGC. This case highlights the
      possibility of a TGC as a differential for retrorectal cystic lesions and the
      need to completely excise them given the possibility of future malignant
      transformation. 

PMID- 25598943
TI  - Transverse testicular ectopia with bilateral pyocoele: case report and brief
      review of literature.
AB  - Transverse testicular ectopia (TTE) is a rare anomaly in which both testis
      descend through a single inguinal canal and enter to same hemiscrotum. To the
      best of our knowledge, we are reporting a new variant of TTE with right inguinal
      hernia with bilateral pyocoele. In this case, both testes descend separately
      through corresponding inguinal canal and present in single right scrotum. There
      is no report of bilateral orchidectomy for this variant of TTE with bilateral
      pyocoele with calcified necrosed testes. We also describe its embryology and
      management in brief, and review the previously reported cases. 

PMID- 25598945
TI  - Aberrant Right Subclavian Artery: A Life-threatening Anomaly that should be
      considered during Esophagectomy.
AB  - Aberrant right subclavian artery (ARSA) is a rare anomaly, in which the right
      subclavian artery arises directly from the aortic arch instead of originating
      from the brachiocephalic artery. This anomaly should be taken into consideration
      during surgical procedures around esophagus, such as esophagectomy. Any
      unintentional injury of this artery during surgical procedures could be extremely
      life threatening. A 56-year-old woman presented with dysphagia, with concurrent
      aberrant subclavian artery and esophageal cancer. The transhiatal esophagectomy
      was performed successfully since the anomaly was preoperatively diagnosed using
      computed tomography scan. The presence of ARSA during esophagectomy may be
      challenging, but if diagnosed preoperatively, the precise and diligent dissection
      of the retroesophageal space during esophagectomy, may prevent any injury to the
      aberrant artery and consequent complications. 

PMID- 25598946
TI  - Pediatric thymoma with a difference: report of a case and review of literature.
AB  - Thymoma represents <1% of all mediastinal tumors in children. Less than 50 cases
      of pediatric thymoma are reported in the literature. Thymomas are considered to
      be highly aggressive in pediatric patients, especially when age is <10 years.
      Paraneoplastic syndromes, of which around 70% are myasthenia gravis, correlate
      with poor prognosis. In this article, we report a case of a thymoma in an 8-year
      old boy, who had favorable histopathology (Masaoka stage I, WHO type B2), despite
      the presence of young age and necrosis along with absence of myasthenia gravis.
      We have also reviewed the available literature on pediatric thymoma. 

PMID- 25598947
TI  - Duodenal Transection without Pancreatic Injury following Blunt Abdominal Trauma.
AB  - With the inventions of faster cars and even more faster motorbikes there is a
      worldwide increase in road traffic accidents, which has increased the incidence
      of blunt abdominal trauma but still duodenal injury following a blunt abdominal
      trauma is uncommon and can pose a formidable challenge to the surgeon and failure
      to manage it properly can result in devastating results. It may typically occur
      in isolation or with pancreatic injury. Here, we report a case of an isolated
      transection of the third part of the duodenum with normal pancreas following a
      blunt abdominal trauma. The initial clinical changes in isolated duodenal injury
      may be extremely subtle before life-threatening, peritonitis develops. Hence, a
      high index of suspicion, on the basis of mechanism of injury and physical
      examination is the key in early detection of duodenal injury especially in a
      rural hospital like ours where the facilities for computed tomography scan are
      not available. 

PMID- 25598948
TI  - Endotracheal intubation challenges to oral cavity - prevention strategy.

PMID- 25598949
TI  - A useful adjunct in lower limb surgery.

PMID- 25598950
TI  - Use of labels on local anaesthetic syringes.

PMID- 25598951
TI  - Culturally Sensitive Intervention for Latina Women with Eating Disorders: A Case
      Study.
AB  - OBJECTIVE: We describe cognitive-behavioral therapy for bulimia nervosa (CBT-BN)
      with a Latina woman that incorporates culturally relevant topics. METHOD: A
      single case report of a 31-year-old monolingual Latina woman with BN describes
      the application of a couple-based intervention adjunctive to CBT-BN. RESULTS: The
      patient reported no binge and purge episodes by session 20 and remained symptom
      free until the end of treatment (session 26). Improvement was observed in the
      Eating Disorders Examination (EDE) comparing baseline (EDE=5.74) with post
      treatment (EDE=1.25). CONCLUSIONS: The case illustrates how cultural adaptations
      such as including a family member, being flexible on topics and scheduling, and
      providing culturally relevant interventions can lead to successful completion of
      a course of therapy and facilitate ongoing interventions to ensure continued
      recovery.

PMID- 25598952
TI  - Differences in Molecular Pathologic Characteristics of Pancreatic Adenocarcinoma
      between Egyptian and Moroccan Patients.
AB  - INTRODUCTION: Pancreatic cancer has not been well studied, especially in
      developing countries. MATERIALS AND METHODS: We studied the variations in genetic
      mutations in pancreatic adenocarcinoma between Moroccan and Egyptian populations.
      The molecular pathology of 30 tumors from a large hospital in Casablanca, Morocco
      were examined and compared with the findings of 44 tumors from the Gharbiah
      Governate in Egypt. K-ras mutations in codons12 and 13 in addition to p53
      mutations in exons 5-8 were evaluated. RESULTS: Overall, differences in the rates
      of K-ras mutations were not statistically significant (48.00 and 34.09%,
      respectively); however differences in rates of p53 mutations were statistically
      significant with p53 mutations more common in Moroccan tumors than in Egyptian
      tumors (46.67 and 16.28%, respectively). GT mutations of the K-ras gene were most
      commonly seen Egyptian tumors, whereas G -> A mutations were the most common type
      of mutations in Moroccan tumors. Logistic regression analysis showed that a p53
      mutation in any exon as well as a p53 mutation in exon 5 predicted the country of
      residence and those mutations occurred more frequently in Moroccan patients.
      CONCLUSION: Our study shows that differences exist within the Arab population in
      the molecular pathology of both the K-ras and p53 genes. Further studies are
      necessary to clarify the differences in molecular pathways of pancreatic cancer
      in the Middle East and to investigate the role of environmental and/or genetic
      factors related to those pathways.

PMID- 25598953
TI  - Evaluation of Distress and Stress in Cancer Patients in AMIR Oncology Hospital in
      Shiraz.
AB  - BACKGROUND: Routine screening for distress is internationally recommended as a
      necessary standard for good cancer care given its high prevalence and negative
      consequences on quality of life. This study attempts to support validation of
      Distress Thermometer (DT) in Shiraz, Iran and in the second step to investigate
      privilege/priority of DT over other referent criterion measures. MATERIAL AND
      METHODS: In total, 58 outpatients with cancer were recruited from AMIR Oncology
      hospital in Shiraz, Iran. Each participant completed the DT and a list of 34
      possible cancer-related problems (the Problem List), the Hospital Anxiety and
      Depression Scale (HADS), the 18-item Brief Symptom Inventory (BSI-18), and a
      short visual analog scale to determine the understandability of the tools.
      RESULTS: Characteristic analysis revealed that DT cutoff scores >=4 and >=5 had
      optimal sensitivity and specificity relative to both HADS and BSI-18 cutoff
      scores for general caseness and more severe psychological distress, respectively.
      Patients with DT scores >=4 (cases) were more likely to be women suffering from
      psychological problems in the past experience stressful events in the 3 years ago
      and encounter more family, emotional, and physical issue related to cancer or
      cancer treatment (p=0.02). CONCLUSION: Patients indicated that the DT was easier
      to fill out and to understand than the HADS, but not the BSI-18. The DT was
      identified as a simple and effective screening instrument for detecting distress
      in Iranian cancer patients as a first step toward more properly referring those
      in need to psychosocial intervention.

PMID- 25598956
TI  - Comparative Evaluation of Iron Deficiency among Obese and Non-obese Children.
AB  - BACKGROUND: Obese children are at the risk of micronutrient deficiency especially
      iron deficiency. Given the importance of iron deficiency in this age group and
      considering the existing discrepancies, present study was performed with the aim
      of evaluating iron deficiency in obese children. MATERIAL AND METHOD: This study
      was conducted, in the form of a case-control study, on 100 children aged between
      5 to 15 during June and November 2013 in Kashan. Cases consisted of 50 obese
      children and controls were 50 children who were not obese.Blood sample was drawn
      to check for serum iron, total iron binding capacity (TIBC) by biochemistry
      method and plasma ferritin by ELISA method. The obtained data were entered into
      SPSS software version 16 and statistically analyzed. P < 0.05 was identified as
      statistically significance. RESULTS: The mean values of serum iron were 52.38 and
      64.50 microg/dL for the case and control groups (P<0.02). TIBC levels in obese
      and non-obese Children were 434.80 and 382.28 microg/dL (P<0.008). The ferritin
      level in the study group was 70.56 versus 68.06 ng/ml in the control group
      (P=0.79). In the obese children group, 8.3% (n=2) of children with iron
      deficiency had ferritin levels less than 15 while in control group 100% (n=14) of
      iron deficient children had ferritin levels below 15 (P<0.001). CONCLUSION: In
      our study, mean serum iron levels were lower among obese children in comparison
      with control group. However, ferritin concentrations were similar in both groups.
      It is supposed that due to inflammatory state caused by obesity, serum ferritin
      levels are naturally higher in obese people. It is suggested that higher levels
      of ferritin considered as normal reference values in obese people.

PMID- 25598954
TI  - Mir-55 inhibition can reduce cell proliferation and induce apoptosis in Jurkat
      (Acute T cell Leukemia) cell line.
AB  - BACKGROUND: MicroRNAs are small and non-coding RNA molecules with approximately
      22 nt in length that cause inhibition of translation or degradation of mRNA. MiR
      155 is a kind of molecule with different functions, such as its role in
      proliferation, apoptosis, inflammation, differentiation, and immunity. One of its
      best known functions is apoptosis that affects on caspase-3 activity. The main
      aim of this study was evaluation of miR-155 inhibition effect on cell
      proliferation and apoptosis induction in Jurkat cells. MATERIAL AND METHODS: In
      this study, Jurkat cells along with MTT assay were used for evaluation of
      sensitivity to varied concentrations of miR-155 inhibitor (25, 50 and 75 nmol).
      MiR-155 expression level was analyzed using the quantitative real-time polymerase
      chain reaction (QRT-PCR). Caspase-3 activity was measured by caspase-3
      colorimetric activity assay kit. Unpaired t-test was applied for the analysis of
      MTT and apoptosis results. Probability of 5% was assumed as statistically
      significant. RESULTS: According to our results, the use of miR-155 inhibitor
      increased the activity of caspase-3 by 2 fold in 75 nmol concentration. In this
      research, we found that the proper increase of miR-155 inhibitor concentration
      can inhibit miR-155 and consequently increase caspase-3 activity and induce
      apoptosis in the Jurkat cells leading to cell death ultimately. CONCLUSIONS:
      Apoptosis induction by miRNAs activation or inhibition is probably one of the
      best and low risk ways of cell death induction in malignancies. Due to role of
      miR-155 in several cancer cells, it may be used as a therapeutic target in
      future.

PMID- 25598955
TI  - The efficacy of recombinant human erythropoietin in treatment chemotherapy
      induced anemia in children diagnosed with a solid cancer.
AB  - BACKGROUND: Recombinant human erythropoietin (rHuEPO) treatment can increase
      hemoglobin levels and decrease transfusion requirements. This study aims to
      investigate how blood transfusion influences Hemoglobin levels in patients
      receiving rHuEPO for 12 weeks. MATERIALS AND METHODS: This was a case-control
      study of 60 patients less than 15 years with anemia and a solid tumor in any
      location between February 2013 and March 2014. Median age of the patients were
      6.27+/-0.58 years (range, 0.9-14 years). The patients were randomly assigned in
      two groups of rHuEPO receiving group and control group. 29 Patients in rHuEPO
      group received 150 IU/kg/dose rHuEPO subcutaneously, 3 times a week, for 12
      weeks. The number of patients received transfusion during the treatment period
      was compared in the preceding 12 weeks. Also, adverse events (AE) were recorded
      at the 4(th), 8(th), and 12(th) weeks. RESULTS: Mean hemoglobin levels, before
      and after study, in rHuEPO group were 8.85+/-1.01 g/dl and 9.90+/-0.29 g/dl,
      respectively (p<0.001) and in control group were, 9.00+/-0.09 g/dl and 7.81+/
      0.23 g/dl, respectively (p=0.25). Among 60 patients initially eligible the
      present study, 57 (29 in rHuEPO group and 28 in control group) completed study
      course.There was a significant decrease in transfusion requirements in the rHuEPO
      receiving group (p=0.004). 5 (17.2%) patients in the rHuEPO group needed a blood
      transfusion, whereas 15 (53.6%) patients needed a transfusion in the control
      group. rHuEPO occasioned hypertension in one patient at 4(th) week that caused to
      end the treatment. All other AE were transient, which did not reoccur after the
      transient discontinuation of the medication (p<0.05). CONCLUSIONS: Results showed
      that the rHuEPO (150 IU/kg/day, 3 times a week) was effective in increasing
      hemoglobin levels as well as decreasing blood transfusion requirements in
      children with anemia following intensive chemotherapy.

PMID- 25598957
TI  - Evaluation of Iron deficiency anemia and BMI in children suffering from
      Helicobacter pylori infection.
AB  - BACKGROUND: Recent studies suggest an association between H. pylori infection and
      disorders such as iron deficiency anemia and growth delay. Considering the high
      prevalence of H. pylori infection and iron deficiency anemia, this study was
      performed in order to evaluate their relevance in children undergoing an upper
      endoscopy. MATERIALS AND METHODS: In this case-control study, children aged 2 to
      16 years old, undergoing endoscopy from March 2012 to March 2013 at Besat
      Hospital of Hamedan, were selected. Participants were divided in H.Pylori
      infected and non-infected groups. Then the two groups were compared in terms of
      body mass index (BMI) and the incidence of iron deficiency anemia. The presence
      of Helicobacter pylori infection in children was confirmed by Giemsa staining of
      gastric biopsy specimens. Collected data was analyzed by SPSS 17.0 (SPSS Inc.,
      Chicago, IL) and t-test and chi-square. RESULTS: In this study, 200 children (94
      male and 106 female) were evaluated. The most common presenting symptom in both
      groups was abdominal pain. 8.2 % (9 cases) of the infected patients and 10.5% (10
      cases) of the non-infected patients had iron deficiency anemia which this
      difference was not statistically significant (p=270). Also, no statistically
      significant difference was noted between the two groups in terms of gender
      (p=0.32), hemoglobin (p=0.35), Ferritin levels (p= 0.275) and body mass index (p=
      0.273). CONCLUSION: The results of this study not showed an association between
      H. pylori infection and iron deficiency anemia or body mass index in studied
      children.

PMID- 25598958
TI  - Dental anomalies and dental age assessment in treated children with acute
      lymphoblastic leukemia.
AB  - BACKGROUND: This cross sectional study was performed to evaluate dental ages and
      incidence of dental anomalies in children treated for acute lymphoblastic
      leukemia (ALL). METHODS AND MATERIALS: A total of 25 ALL patient who passed at
      least 2 years of chemotherapy and 25 healthy sex and age matched children were
      evaluated. Dental age as well as dental anomalies in shape, size, number, and
      structure was recorded based on their panoramic radiographies which were taken
      for dental purposes. RESULTS: The number of dental anomalies significantly
      increased in ALL treated children. Seven ALL cases (28%) in compression to only
      one (4%) in control group had at least one dental anomaly. However, there was
      neither statistically significant differences between the mean of dental (p=0.32)
      and chronologic age (p=0.12) in both groups, nor between dental age of cases and
      control group (p=0.62).The age at the onset of treatment as well as treatment
      durations has not affected dental age and the incidence of dental anomalies
      significantly (p<0.05). CONCLUSION: Chemotherapy in children results in emergence
      of dental anomaly. Dental age, maturity, and development process however seems to
      be independent from chemotherapy.

PMID- 25598960
TI  - A Case Report: Acute Myeloid Leukemia (FAB M7).
AB  - Acute myeloid leukemia (AML-M7) is a type of pediatric AML accounting for 3-10%
      of primary childhood AML and children may present with a broad variety of
      symptoms including low-grade fever, diarrhea, easy bruising, failure to gain
      weight and life-threatening conditions. We report a rare case of AML .A 26-month
      old boy who presented with weakness and fatigue. He was diagnosed as a case of
      AMLM-7 on the basis of peripheral blood finding, bone marrow examination report
      and immune phenotyping. 

PMID- 25598961
TI  - The Elusiveness of a Life-span Model of Emotion Regulation.

PMID- 25598962
TI  - In Vivo Visible Light-Triggered Drug Release From an Implanted Depot.
AB  - Controlling chemistry in space and time has offered scientists and engineers
      powerful tools for research and technology. For example, on-demand photo
      triggered activation of neurotransmitters has revolutionized neuroscience. Non
      invasive control of the availability of bioactive molecules in living organisms
      will undoubtedly lead to major advances; however, this requires the development
      of photosystems that efficiently respond to regions of the electromagnetic
      spectrum that innocuously penetrate tissue. To this end, we have developed a
      polymer that photochemically degrades upon absorption of one photon of visible
      light and demonstrated its potential for medical applications. Particles
      formulated from this polymer release molecular cargo in vitro and in vivo upon
      irradiation with blue visible light through a photoexpansile swelling mechanism.

PMID- 25598963
TI  - Echinoderm conundrums: Hox genes, heterochrony, and an excess of mouths.
AB  - Two issues relating to the translocation of anterior Hox genes in echinoderms to
      the 5' end of the Hox cluster are discussed: i) that developmental changes
      associated with fixation to the substratum have led to an acceleration of
      mesodermal development relative to that of ectoderm, resulting in a mismatch of
      anteroposterior registry between the two tissues and a larger role for mesoderm
      in patterning control, and ii) whether this helps explain the ability of some
      echinoderms to form separate mouths at different locations, one for the larva and
      one for the juvenile rudiment. Freeing the mesoderm from ectodermal influences
      may have encouraged morphogenetic innovation, paralleling the situation in
      tunicates, where an early genomic (or genomic and developmental) change has
      allowed the body to evolve in novel ways. 

PMID- 25598959
TI  - Hepatitis B virus infection in patients with blood disorders: a concise review in
      pediatric study.
AB  - Childhood Hepatitis B virus (HBV) infection causes both medical and public health
      challenges. Infants who acquire HBV parentally have up to 90% risk of developing
      chronic HBV infection. It is now estimated that approximately 10% of worldwide
      cancers are attributable to viral infection, with the vast majority (>85 %)
      occurring in the developing world. In this distribution, elevated rate and
      prevalence of HBV marker have been found in patients with malignancies as
      compared to the general population. By reviewing the web-based search for all
      Persian and English types of scientific peer review published articles initiated
      using Iran Medex, MEDLINE/PubMed, CINAHL and other pertinent references on
      websites about HBV and HCV blood disorders. The high prevalence of HBV and HCV
      infective markers was detected in patients with different malignancies. Moreover,
      identification of high prevalence of HBV infective markers in leukemia patients
      proposed strong association between hepatitis viral infections and leukemia. 

PMID- 25580222
TI  - Role of bacteriophages in STEC infections: new implications for the design of
      prophylactic and treatment approaches.
AB  - Shiga toxin (Stx) is considered the main virulence factor in Shiga toxin
      producing Escherichia coli (STEC) infections. Previously we reported the
      expression of biologically active Stx by eukaryotic cells in vitro and in vivo
      following transfection with plasmids encoding Stx under control of the native
      bacterial promoter (1,2). Since stx genes are present in the genome of lysogenic
      bacteriophages, here we evaluated the relevance of bacteriophages during STEC
      infection. We used the non-pathogenic E. coli C600 strain carrying a lysogenic
      933W mutant bacteriophage in which the stx operon was replaced by a gene encoding
      the green fluorescent protein (GFP). Tracking GFP expression using an In Vivo
      Imaging System (IVIS), we detected fluorescence in liver, kidney, and intestine
      of mice infected with the recombinant E. coli strain after treatment with
      ciprofloxacin, which induces the lytic replication and release of bacteriophages.
      In addition, we showed that chitosan, a linear polysaccharide composed of d
      glucosamine residues and with a number of commercial and biomedical uses, had
      strong anti-bacteriophage effects, as demonstrated at in vitro and in vivo
      conditions. These findings bring promising perspectives for the prevention and
      treatment of haemolytic uremic syndrome (HUS) cases. 

PMID- 25580223
TI  - Does the linear Sry transcript function as a ceRNA for miR-138? The sense of
      antisense.
AB  - Recently, the sex determining region Y ( Sry) and the cerebellar degeneration
      related protein 1 ( CDR1as) RNA transcripts have been described to function as a
      new class of post-transcriptional regulatory RNAs that behave as circular
      endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7,
      respectively. A special feature of the Sry gene is its ability to generate linear
      and circular transcripts, both transcribed in the sense orientation. Here we
      remark that both sense (e.g. Sry RNA) and antisense (e.g. CDR1as) transcripts
      could circularize and behave as miRNAs sponges, and importantly, that also
      protein-coding segments of mRNAs could also assume this role. Thus, it is
      reasonable to think that the linear Sry sense transcript could additionally act
      as a miRNA sponge, or as an endogenous competing RNA for miR-138. 

PMID- 25580229
TI  - The F1000Research Antibody Validation Article Collection.
AB  - Well validated antibodies are crucial to progress in a wide range of life science
      disciplines, but validating an antibody is a complex and ongoing process.
      Antibody validation is often carried out as preliminary work to a larger study so
      the validation data may go unpublished and needless duplication of efforts can
      occur. This collection of articles in F1000Research provides a home for papers
      describing antibody validation studies. Our goal is to encourage publishing of
      all studies, both positive and negative, which increase understanding of how
      antibodies perform. These could range from large studies with thousands of
      antibodies to small single figure studies which validate an individual antibody
      for a specific purpose. Opinion or Correspondence articles considering any aspect
      of antibody validation are also welcome. Here, we provide an introduction to the
      collection which we hope will grow and become a valuable resource for the many
      thousands of researchers who use antibodies. 

PMID- 25580228
TI  - Stress, rejection, and hormones: Cortisol and progesterone reactivity to
      laboratory speech and rejection tasks in women and men.
AB  - Stress and social rejection have important impacts on health. Among the
      mechanisms implicated are hormonal systems such as the hypothalamic-pituitary
      adrenal (HPA) axis, which produces cortisol in humans. Current research employs
      speech stressors and social rejection stressors to understand hormonal responses
      in a laboratory setting. However, it is not clear whether social rejection
      stressors elicit hormonal reactivity. In addition to cortisol, progesterone has
      been highlighted as a potential stress- and affiliation-related hormone in
      humans. In the present study, 131 participants (70 men and 61 women) were
      randomly assigned to be exposed to one of four conditions: standardized speech
      stressor; speech control; social rejection task; or a control (inclusion) version
      of the social rejection task. Saliva samples were collected throughout the study
      to measure cortisol and progesterone. As hypothesized, we found the expected
      increase in cortisol in the speech stressor, and we also found that the social
      rejection task did not increase cortisol, underscoring the divergence between
      unpleasant experiences and HPA axis activity. However, we did not find evidence
      for progesterone increase either during the speech- or social rejection tasks.
      Compared with past studies on progesterone and stress in humans, the present
      findings present a mixed picture. Future work is needed to delineate the contexts
      and types of manipulations which lead to progesterone increases in humans. 

PMID- 25580225
TI  - Why are neurotransmitters neurotoxic? An evolutionary perspective.
AB  - In the CNS, minor changes in the concentration of neurotransmitters such as
      glutamate or dopamine can lead to neurodegenerative diseases. We present an
      evolutionary perspective on the function of neurotransmitter toxicity in the CNS.
      We hypothesize that neurotransmitters are selected because of their toxicity,
      which serves as a test of neuron quality and facilitates the selection of
      neuronal pathways. This perspective may offer additional explanations for the
      reduction of neurotransmitter concentration in the CNS with age, and suggest an
      additional role for the blood-brain barrier. It may also suggest a connection
      between the specific toxicity of the neurotransmitters released in a specific
      region of the CNS, and elucidate their role as chemicals that are optimal for
      testing the quality of cells in that region. 

PMID- 25598969
TI  - Real-Time Detection of Telomerase Activity in Cancer Cells using a Label-Free
      Electrochemical Impedimetric Biosensing Microchip.
AB  - The enzyme telomerase is present in about 85% of human cancers which makes it not
      only a good target for cancer treatment but also an excellent marker for cancer
      detection. Using a single stranded DNA probe specific for telomerase binding and
      reverse transcription tethered to an interdigital gold electrode array surface,
      the chromosome protection provided by the telomerase was replicated and followed
      by Electrochemical Impedance Spectroscopy as an unlabeled biosensor. Using this
      system designed in-house, easy and affordable, impedance measurements were taken
      while incubating at 37  degrees C and promoting the probe elongation. This
      resulted in up to 14-fold increase in the charge transfer resistance when testing
      a telomerase-positive nuclear extract from Jurkat cells compared to the heat
      inactivated telomerase-negative nuclear extract. The electron transfer process at
      the Au electrodes was studied before the elongation, at different times after the
      elongation, and after desorption of non-specific binding.

PMID- 25598970
TI  - Development of a microfluidic "click chip" incorporating an immobilized Cu(I)
      catalyst.
AB  - We have developed a microfluidic "click chip" incorporating an immobilized Cu(I)
      catalyst for click reactions. The microfluidic device was fabricated from
      polydimethylsiloxane (PDMS) bonded to glass and featured ~14,400 posts on the
      surface to improve catalyst immobilization. This design increased the
      immobilization efficiency and reduces the reagents' diffusion time to active
      catalyst site. The device also incorporates five reservoirs to increase the
      reaction volume with minimal hydrodynamic pressure drop across the device. A
      novel water-soluble tris-(benzyltriazolylmethyl)amine (TBTA) derivative capable
      of stabilizing Cu(I), ligand 2, was synthesized and successfully immobilized on
      the chip surface. The catalyst immobilized chip surface was characterized by X
      ray photoelectron spectroscopy (XPS). The immobilization efficiency was evaluated
      via radiotracer methods: the immobilized Cu(I) was measured as 1136+/-272 nmol
      and the surface immobilized Cu(I) density was 81+/-20 nmol cm-2. The active Cu(I)
      ligand 2 could be regenerated up to five times without losing any catalyst
      efficiency. The "click" reaction of Flu568-azide and propargylamine was studied
      on chip for proof-of-principle. The on-chip reaction yields were ca. 82% with a
      50 min reaction time or ca. 55% with a 15 min period at 37  degrees C, which was
      higher than those obtained in the conventional reaction. The on-chip "click"
      reaction involving a biomolecule, cyclo(RGDfK) peptide was also studied and
      demonstrated a conversion yield of ca. 98%. These encouraging results show
      promise on the application of the Cu(I) catalyst immobilized "click chip" for the
      development of biomolecule based imaging agents.

PMID- 25598971
TI  - Hospital- and patient-related factors associated with differences in hospital
      antibiotic use: analysis of national surveillance results.
AB  - BACKGROUND: Surveillance data of antibiotic use are increasingly being used for
      benchmarking purposes, but there is a lack of studies dealing with how hospital-
      and patient-related factors affect antibiotic utilization in hospitals. Our
      objective was to identify factors that may contribute to differences in
      antibiotic use. METHODS: Based on pharmacy sales data (2006-2011), use of all
      antibiotics, all penicillins, and broad-spectrum antibiotics was analysed in 22
      Health Enterprises (HEs). Antibiotic utilization was measured in World Health
      Organisation defined daily doses (DDDs) and hospital-adjusted (ha)DDDs, each
      related to the number of bed days (BDs) and the number of discharges. For each
      HE, all clinical specialties were included and the aggregated data at the HE
      level constituted the basis for the analyses. Fourteen variables potentially
      associated with the observed antibiotic use - extracted from validated national
      databases - were examined in 12 multiple linear regression models, with four
      different measurement units: DDD/100 BDs, DDD/100 discharges, haDDD/100 BDs and
      haDDD/100 discharges. RESULTS: Six variables were independently associated with
      antibiotic use, but with a variable pattern depending on the regression model.
      High levels of nurse staffing, high proportions of short (<2 days) and long (>10
      days) hospital stays, infectious diseases being the main ICD-10 diagnostic codes,
      and surgical diagnosis-related groups were correlated with a high use of all
      antibiotics. University affiliated HEs had a lower level of antibiotic
      utilization than other institutions in eight of the 12 models, and carried a high
      explanatory strength. The use of broad-spectrum antibiotics correlated strongly
      with short and long hospital stays. There was a residual variance (30%-50% for
      all antibiotics; 60%-70% for broad-spectrum antibiotics) that our analysis did
      not explain. CONCLUSIONS: The factors associated with hospital antibiotic use
      were mostly non-modifiable. By adjusting for these factors, it will be easier to
      evaluate and understand observed differences in antibiotic use between hospitals.
      Consequently, the inter-hospital differences can be more confidently acted upon.
      The residual variation is presumed to largely reflect prescriber-related factors.

PMID- 25598972
TI  - Computational conformational antimicrobial analysis developing mechanomolecular
      theory for polymer biomaterials in materials science and engineering.
AB  - Single-bond rotations or pyramidal inversions tend to either hide or expose
      relative energies that exist for atoms with nonbonding lone-pair electrons.
      Availability of lone-pair electrons depends on overall molecular electron
      distributions and differences in the immediate polarity of the surrounding
      pico/nanoenvironment. Stereochemistry three-dimensional aspects of molecules
      provide insight into conformations through single-bond rotations with associated
      lone-pair electrons on oxygen atoms in addition to pyramidal inversions with
      nitrogen atoms. When electrons are protected, potential energy is sheltered
      toward an energy minimum value to compatibilize molecularly with nonpolar
      environments. When electrons are exposed, maximum energy is available toward
      polar environment interactions. Computational conformational analysis software
      calculated energy profiles that exist during specific oxygen ether single-bond
      rotations with easy-to-visualize three-dimensional models for the trichlorinated
      bisaromatic ether triclosan antimicrobial polymer additive. As shown, fluctuating
      alternating bond rotations can produce complex interactions between molecules to
      provide entanglement strength for polymer toughness or alternatively disrupt weak
      secondary bonds of attraction to lower resin viscosity for new additive
      properties with nonpolar triclosan as a hydrophobic toughening/wetting agent.
      Further, bond rotations involving lone-pair electrons by a molecule at a nonpolar
      hydrocarbon-membrane/polar-biologic-fluid interface might become sufficiently
      unstable to provide free mechanomolecular energies to disrupt weaker microbial
      membranes, for membrane transport of molecules into cells, provide cell
      signaling/recognition/defense and also generate enzyme mixing to speed reactions.

PMID- 25598974
TI  - Implementation and evaluation of a rapid access palliative clinic in a New
      Zealand cancer centre.
AB  - INTRODUCTION: Palliative patients with metastatic bone pain endure long waiting
      times and multiple visits to radiation therapy departments for treatment. This
      can prolong suffering and may be a factor in patients consenting for treatment.
      Rapid Access Palliative Clinics (RAPC) have been established around the world to
      provide a multidisciplinary approach to consultation, simulation and treatment on
      the same day. This paper describes the implementation and evaluation of a RAPC at
      Waikato Regional Cancer Centre (WRCC) by reducing the time from referral to first
      specialist appointment (FSA). METHODS: The structure and process for the RAPC day
      was outlined and the roles of staff were defined. A retrospective study was
      undertaken of the 261 consecutive patients seen in the RAPC from April 2009 to
      April 2013. Tracking sheets were created to record patient information at the
      initial consultation. Follow-up telephone calls were used to assess the patient
      post-treatment. Patient information was entered into a database. RESULTS: A total
      of 226 patients received radiation therapy treatment to 307 sites. All patients
      were seen within 1 week of referral. Sixty-three per cent of patients were
      simulated and treated on the same day. The change in radiation therapy
      fractionation prescriptions was statistically significant (P = 0.0012). There was
      a statistically significant difference between initial and follow-up pain scores
      (P < 0.0001). CONCLUSION: Evaluation of the clinic has shown that it compares
      favourably with similar international clinics. The RAPC has decreased the
      referral to FSA for palliative radiation therapy and reduced the number of visits
      the patient has to endure due to an increase in single fraction prescriptions.
      This has resulted in rapid reduction in pain for the majority of patients.

PMID- 25598973
TI  - CD200 in CNS tumor-induced immunosuppression: the role for CD200 pathway blockade
      in targeted immunotherapy.
AB  - BACKGROUND: Immunological quiescence in the central nervous system (CNS) is a
      potential barrier to immune mediated anti-tumor response. One suppressive
      mechanism results from the interaction of parenchyma-derived CD200 and its
      receptor on myeloid cells. We suggest that CD200/CD200R interactions on myeloid
      cells expand the myeloid-derived suppressor cell (MDSC) population and that
      blocking tumor-derived CD200 will enhance the efficacy of immunotherapy. METHODS:
      CD200 mRNA expression levels in human brain tumor tissue samples were measured by
      microarray. The amount of circulating CD200 protein in the sera of patients with
      brain tumors was determined by ELISA and, when corresponding peripheral blood
      samples were available, was correlated quantitatively with MDSCs. CD200-derived
      peptides were used as competitive inhibitors in a mouse model of glioblastoma
      immunotherapy. RESULTS: CD200 mRNA levels were measured in human brain tumors,
      with different expression levels being noted among the sub groups of
      glioblastoma, medulloblastoma and ependymoma. Serum CD200 concentrations were
      highest in patients with glioblastoma and correlated significantly with MDSC
      expansion. Similarly, in vitro studies determined that GL261 cells significantly
      expanded a MDSC population. Interestingly, a CD200R antagonist inhibited the
      expansion of murine MDSCs in vitro and in vivo. Moreover, inclusion of CD200R
      antagonist peptide in glioma tumor lysate-derived vaccines slowed tumor growth
      and significantly enhanced survival. CONCLUSION: These data suggest that CNS
      derived tumors can evade immune surveillance by engaging CD200. Because of the
      homology between mouse and human CD200, our data also suggest that blockade of
      CD200 binding to its receptor will enhance the efficacy of immune mediated anti
      tumor strategies for brain tumors.

PMID- 25598975
TI  - A cross-sectional study of stressors and coping mechanisms used by radiation
      therapists and oncology nurses: Resilience in Cancer Care Study.
AB  - INTRODUCTION: Occupational stress and burnout are well-recognised experiences
      reported by cancer care workers. The aim was to describe the frequency and
      severity of potential stressors as well as the effectiveness of coping skills of
      radiation therapists (RTs) and oncology nurses (ONs), which make up the two
      largest occupational groups in cancer care. METHODS: A questionnaire was
      distributed to RTs and ONs in two large tertiary hospitals in Queensland.
      Descriptive data regarding severity of potential stressors at home and work as
      well as the perceived effectiveness of preferred coping styles for each stressor
      was compared for each professional group. Respondents were asked questions about
      their personal circumstances and to also complete five standardised
      questionnaires measuring resilience, mental well-being, depression, anxiety and
      burnout. RESULTS: There were 71 respondents representing a response rate of 26%.
      The types of stressors differed between the two groups but both reported that
      heavy workload was the most severe workplace stressor. RTs reported higher
      stressor and coping strategy frequency than ONs. There were no identifiable
      differences between RTs and ONs in the types or effectiveness of coping
      strategies employed at home or work. Mental well-being for both groups was
      inversely correlated with depression, anxiety and burnout and positively
      correlated with resilience. CONCLUSIONS: RTs experienced higher mean scores for
      stressors and coping than ONs. There were no significant between-group
      differences for anxiety, depression, burnout, mental well-being or resilience.

PMID- 25598977
TI  - Clinical perceptions of radiation therapy undergraduate competency standards.
AB  - INTRODUCTION: The multifactorial nature of clinical skills development makes
      assessment of undergraduate radiation therapist competence level by clinical
      mentors challenging. A recent overhaul of the clinical assessment strategy at
      Queensland University of Technology has moved away from the high-stakes Objective
      Structured Clinical Examination (OSCE) to encompass a more continuous measure of
      competence. This quantitative study aimed to gather stakeholder evidence to
      inform development of standards by which to measure student competence for a
      range of levels of progression. METHODS: A simple anonymous questionnaire was
      distributed to all Queensland radiation therapists. The tool asked respondents to
      assign different levels of competency with a range of clinical tasks to different
      levels of student. All data were anonymous and was combined for analysis using
      Microsoft Excel. RESULTS: Feedback indicated good agreement with tasks that
      specified the amount of direction required and this has been incorporated into
      the new clinical achievements record that the students need to have signed off.
      Additional puzzling findings suggested higher expectations with planning tasks
      than with treatment-based tasks. CONCLUSION: The findings suggest that the amount
      of direction required by students is a valid indicator of their level and has
      been adopted into the clinical assessment scheme. Further work will build on this
      to further define standards of competency for undergraduates.

PMID- 25598976
TI  - The masked educator-innovative simulation in an Australian undergraduate Medical
      Sonography and Medical Imaging program.
AB  - INTRODUCTION: Clinical learning experiences for sonography and medical imaging
      students can sometimes involve the practice of technical procedures with less of
      a focus on developing communication skills with patients. Whilst patient-based
      simulation scenarios have been widely reported in other health education
      programmes, there is a paucity of research in sonography and medical imaging. The
      aim of this study was to explore the effectiveness of Mask-EdTM (KRS Simulation)
      in the learning and teaching of clinical communication skills to undergraduate
      medical sonography and medical imaging students. Mask-EdTM (KRS Simulation) is a
      simulation technique where the educator is hidden behind wearable realistic
      silicone body props including masks. METHODS: Focus group interviews were
      conducted with 11 undergraduate medical sonography and medical imaging students
      at CQUniversity, Australia. The number of participants was limited to the size of
      the cohort of students enrolled in the course. Prior to these interviews
      participants were engaged in learning activities that featured the use of the
      Mask-EdTM (KRS Simulation) method. Thematic analysis was employed to explore how
      the introduction of Mask-EdTM (KRS Simulation) contributed to students' learning
      in relation to clinical communication skills. RESULTS: Key themes included:
      benefits of interacting with someone real rather than another student, learning
      made fun, awareness of empathy, therapeutic communication skills, engaged problem
      solving and purposeful reflection. CONCLUSIONS: Mask-EdTM (KRS Simulation)
      combined with interactive sessions with an expert facilitator, contributed
      positively to students' learning in relation to clinical communication skills.
      Participants believed that interacting with someone real, as in the Mask-Ed
      characters was beneficial. In addition to the learning being described as fun,
      participants gained an awareness of empathy, therapeutic communication skills,
      engaged problem solving and purposeful reflection.

PMID- 25598978
TI  - Quality improvement process to assess tattoo alignment, set-up accuracy and
      isocentre reproducibility in pelvic radiotherapy patients.
AB  - INTRODUCTION: This quality improvement study tested three methods of tattoo
      alignment and isocentre definition to investigate if aligning lateral tattoos to
      minimise pitch, roll and yaw decreased set-up error, and if defining the
      isocentre using the lateral tattoos for cranio-caudal (CC) position improved
      isocentre reproducibility. The study population was patients receiving curative
      external beam radiotherapy (EBRT) for prostate cancer. The results are applicable
      to all supine pelvic EBRT patients. METHODS: The three sequential cohorts
      recruited 11, 11 and 10 patients respectively. A data set of 20 orthogonal pairs
      of electronic portal images (EPI) was acquired for each patient. EPIs were
      matched offline to digitally reconstructed radiographs. In cohort 1, lateral
      tattoos were adjusted to minimise roll. The anterior tattoo was used to define
      the isocentre. In cohort 2, lateral tattoos were aligned to minimise roll and
      yaw. Isocentre was defined as per cohort 1. In cohort 3, lateral tattoos were
      aligned as per cohort 2 and the anterior tattoo was adjusted to minimise pitch.
      Isocentre was defined by the lateral tattoos for CC position and the anterior
      tattoo for the left-right position. RESULTS: Cohort 3 results were superior as CC
      systematic and random set-up errors reduced from -1.3 mm to -0.5 mm, and 3.1 mm
      to 1.4 mm respectively, from cohort 1 to cohort 3. Isocentre reproducibility also
      improved from 86.7% to 92.1% of treatment isocentres within 5 mm of the planned
      isocentre. CONCLUSION: The methods of tattoo alignment and isocentre definition
      in cohort 3 reduced set-up errors and improved isocentre reproducibility.

PMID- 25598979
TI  - Comparison of four 3D conformal treatment techniques to optimise radiotherapy
      treatment for anal cancer.
AB  - INTRODUCTION: Chemoradiotherapy is the standard of care for anal cancer. Sizeable
      target volume leads to significant toxicity. We compared four different 3D
      conformal radiotherapy (3DCRT) techniques with the aim of finding the best
      technique to achieve the lowest dose to the organs at risk (OAR) without
      compromising the planning target volume (PTV) coverage. METHODS: Fifteen computed
      tomography (CT) data sets from previously treated anal cancer patients (five male
      and 10 female) were re-contoured according to the Australasian Gastrointestinal
      Trials Group (AGITG) anal cancer contouring guidelines for N3 disease. Four
      different 3DCRT plans for each CT data set (standard, V-shape, diamond shape and
      alternate diamond shape) were generated. Comparisons of the radiation dose to non
      rectal bowel (NRB), urinary bladder, genitalia, and femurs were performed.
      RESULTS: V-shape technique achieved significantly lower NRB V40 (mean = 59.6% SD
      = 11%) than diamond (63.8% SD = 13%), standard (63.8% SD = 11%) and alternate
      diamond (63.6% SD = 12%) techniques. V-shape technique achieved the lowest mean
      bladder dose (mean = 45.3 Gy SD = 1.4 Gy). Diamond technique achieved the lowest
      femur V40 (mean = 32.4%) P < 0.001 for all comparisons between diamond and all
      other techniques. For genitalia V40, diamond technique (mean = 26.4% SD = 20%)
      and alternate diamond technique (mean = 27.6% SD = 20%) achieved significantly
      lower dose than V-shape technique (mean = 43.2% SD = 26%) and standard technique
      (mean = 76.1% SD = 16%) P < 0.001 for all comparisons. CONCLUSIONS: Sophisticated
      3DCRT techniques are superior to conventional techniques. Different 3DCRT
      techniques provide varying levels of dose reduction to OAR, with none of the four
      techniques investigated capable of reducing dose to all OAR. A combination of
      techniques may provide the best solution. Further refinement of these techniques
      should be explored.

PMID- 25598982
TI  - Acknowledging the peer reviewers from October 2013 - September 2014.

PMID- 25598980
TI  - The quality assurance of volumetric modulated arc therapy (VMAT) plans for early
      stage prostate cancer: a technical note.
AB  - As radiation therapy transitions from intensity modulated radiation therapy
      (IMRT) to volumetric modulated arc therapy (VMAT) it is important to consider the
      quality assurance (QA) of VMAT plans in light of what has previously been learned
      and developed in IMRT QA. This technical note assesses if IMRT based plan QA
      software, which has reduced the need in IMRT for phantom dose measurements on the
      linear accelerator, can be incorporated into VMAT QA processes. Twenty prostate
      cases were retrospectively planned using VMAT with one arc to deliver a
      prescription of 74 Gy in 37 fractions. A plan QA was performed using both IMSure
      (version 3.3), a software-based IMRT QA program, and ArcCHECK (version
      6.2.3.5713), a phantom-based VMAT QA tool. Outcomes assessed included the time
      needed to perform the QA of both the IMSure and ArcCHECK QA methods, and
      agreement between planned dose and QA measured dose. On average per case, the
      ArcCHECK technique needed 31.5 min to perform the VMAT plan QA, while IMSure
      required 3.5 min to perform the same QA. All 20 cases passed dosimetric QA using
      ArcCHECK. However, using IMSure, three cases failed dosimetric QA using the
      departments existing IMRT QA criteria. This research has demonstrated that the
      IMRT QA software IMSure may be incorporated into the QA of VMAT plans, however
      the criteria to assess the dosimetry of the VMAT plans may need to be different
      to that for IMRT cases. The implication of this research for radiation therapists
      is to be critically aware of the differences between the plan QA requirements and
      methods for IMRT and those required for VMAT.

PMID- 25598981
TI  - The feasibility and benefits of using volumetric arc therapy in patients with
      brain metastases: a systematic review.
AB  - INTRODUCTION: Radiotherapy management of patients with brain metastases most
      commonly involve a whole-brain radiation therapy (WBRT) regime, as well as newer
      techniques such as stereotactic radiosurgery (SRS) and intensity modulated
      radiotherapy (IMRT). The long treatment times incurred by these techniques
      indicates the need for a novel technique that has shorter treatment times, whilst
      still producing highly conformal treatment with the potential to deliver
      escalated doses to the target area. Volumetric modulated arc therapy (VMAT) is a
      dynamic, highly conformal technique that may deliver high doses of radiation
      through a single gantry arc and reduce overall treatment times. The aim of this
      systematic review is to determine the feasibility and benefits of VMAT treatment
      in regard to overall survival rates and local control in patients with brain
      metastases, in comparison with patients treated with WBRT, SRS and IMRT. METHODS:
      A search of the literature identified 23 articles for the purpose of this review.
      Articles were included on the basis they were human-based studies, with sample
      sizes of more than five patients who were receiving treatment for 1-10 metastatic
      brain lesions. RESULTS: VMAT was found to be highly conformal, have a reduced
      treatment delivery time and incurred no significant toxicities in comparison with
      WBRT, SRS and IMRT. CONCLUSION: Compared to other treatment techniques, VMAT
      proved to have fewer toxicities than conventional WBRT, shorter treatment times
      than SRS and similar dose distributions to IMRT plans. Future prospective studies
      are needed to accurately assess the prognostic benefits of VMAT as well as the
      occurrence of late toxicities.

PMID- 25598983
TI  - Physical rehabilitation improves muscle function following volumetric muscle loss
      injury.
AB  - BACKGROUND: Given the clinical practice of prescribing physical rehabilitation
      for the treatment of VML injuries, the present study examined the functional and
      histomorphological adaptations in the volumetric muscle loss (VML) injured muscle
      to physical rehabilitation. METHODS: Tibialis anterior muscle VML injury was
      created in Lewis rats (n = 32), and were randomly assigned to either sedentary
      (SED) or physical rehabilitation (RUN) group. After 1 week, RUN rats were given
      unlimited access to voluntary running wheels either 1 or 7 weeks (2 or 8 weeks
      post-injury). At 2 weeks post-injury, TA muscles were harvested for molecular
      analyses. At 8 weeks post-injury, the rats underwent in vivo function testing.
      The explanted tissue was analyzed using histological and immunofluorescence
      procedures. RESULTS: The primary findings of the study are that physical
      rehabilitation in the form of voluntary wheel running promotes ~ 17% improvement
      in maximal isometric torque, and a ~ 13% increase in weight of the injured
      muscle, but it did so without significant morphological adaptations (e.g., no
      hypertrophy and hyperplasia). Wheel running up-regulated metabolic genes (SIRT-1,
      PGC-1alpha) only in the uninjured muscles, and a greater deposition of fibrous
      tissue in the defect area of the injured muscle preceded by an up-regulation of
      pro-fibrotic genes (Collagen I, TGF-beta1). Therefore, it is plausible that the
      wheel running related functional improvements were due to improved force
      transmission and not muscle regeneration. CONCLUSIONS: This is the first study to
      demonstrate improvement in functional performance of non-repaired VML injured
      muscle with physical rehabilitation in the form of voluntary wheel running. This
      study provides information for the first time on the basic changes in the VML
      injured muscle with physical rehabilitation, which may aid in the development of
      appropriate physical rehabilitation regimen(s).

PMID- 25598984
TI  - The effect of external ankle support on the kinematics and kinetics of the lower
      limb during a side step cutting task in netballers.
AB  - BACKGROUND: Excessive knee valgus moments are considered to be a risk factor for
      non-contact injuries in female athletes. Knee injuries are highly prevalent in
      netballers and are significant in terms of cost and disability. The aim of the
      study was to identify if changes in external ankle support mechanisms effect the
      range of motion and loading patterns at the ankle and knee joint during a
      sidestep cutting manoeuvre in high performance netball players. METHODS:
      Netballers with no previously diagnosed ankle or knee injury (n = 10) were
      recruited from NSW Institute of Sport netball programme. Kinematic and kinetic
      data were collected simultaneously using a 3-D Motion Analysis System and a force
      platform to measure ground reaction forces. Players performed repeated side step
      cutting manoeuvres whilst wearing a standard netball shoe, the same shoe with a
      lace-up brace and a high-top shoe. RESULTS: The brace condition significantly
      reduced ankle joint ROM in the sagittal plane by 8.9 degrees  +/- 2.4 when
      compared to the standard netball shoe (p = 0.013). No other significant changes
      were seen between conditions for either kinematic or kinetic data. All shoe
      conditions did however produce knee valgus moments throughout the cutting cycle
      that were greater than those considered excessive in the previous literature
      (0.59 Nm/kg-Bwt). CONCLUSIONS: The results show that an external ankle support
      brace can be used to reduce the ROM at the ankle in the sagittal plane without
      affecting the loading of the joints of the lower limb. Internal varus moments
      generated at the knee during the task were however greater than values reported
      in the literature to classify excessive knee joint moments, regardless of the
      condition. All netballers exhibited lower extremity patterns and alignments
      previously associated with increased peak external valgus moments including;
      increasing hip abduction, peak hip flexion and internal rotation during early
      contact and high laterally directed ground reaction forces. Increased external
      valgus knee loads have been strongly linked to the development of non-contact
      injuries at the knee in female athletes and could highlight a potential mechanism
      for the development non-contact knee injuries in netballers performing side step
      cutting tasks.

PMID- 25598985
TI  - Factors influencing older black women's sexual functioning and their disclosure
      of sexual concerns.
AB  - INTRODUCTION: The study of older women's sexual health has been very limited.
      Most of the available research in this area is on Caucasian older women; a few
      studies have targeted the sexuality of older Black women. There could be several
      reasons for this and for the common reluctance of these women to disclose
      information on their sexual health. The aim of this review was to discuss factors
      influencing older black women's sexual functioning and their disclosure of sexual
      concerns. DISCUSSION: In this article, we first briefly reviewed the literature
      on sexual health among older women, then covered historical and social issues
      that are likely to influence older Black women's sexuality as well as their
      common reluctance to disclose intimate details of their lives to their health
      providers. This information could be important for researchers as well as
      healthcare professionals. Specific groups of clinicians potentially interested in
      this discussion are sexual health professionals, couples' counsellors as well as
      other professionals attempting to address older patients' problems such as
      relationship, intimacy and sex challenges. Without knowledge of critical issues
      such as the potentially traumatizing historical events and the multiple societal
      pressures that are likely to impact these women's sexuality and disclosure of
      sexual concerns, it would be difficult for researchers and clinicians to get an
      accurate account of older Black women's sexual needs. CONCLUSION: Older Black
      women's sexuality is a very delicate and complex topic. We encourage interested
      professionals to make an effort to become more aware of what is potentially
      holding back older Black women from disclosing their sexual concerns to them, and
      have provided some historical information and research suggestions to guide
      professionals interested in investigating older African American women's
      sexuality in a more tactful and culturally-sensitive way.

PMID- 25598987
TI  - Risk of local failure after ultrasound guided irreversible electroporation of
      malignant liver tumors.
AB  - INTRODUCTION: Irreversible electroporation (IRE) is considered superior to
      thermoablations for tumors in the vicinity of larger vessels and the liver hilum.
      We report on an initial clinical experience of IRE. MATERIALS AND METHODS:
      Indications included focal liver lesions <3 cm, irresectability due to
      contraindications and expected complications and/or irradicality following
      radiofrequency ablation (RFA). Ultrasound was chosen for guidance and needle
      placement. RESULTS: IRE was intended to perform in 14 patients with 1 procedure
      aborted due to technical failure. Among the 13 successfully treated were 7
      percutaneous, 4 laparoscopic, and 2 open surgical procedures. The average age was
      63 +/- 10 years. Twelve solitary nodules and one bifocal disease were treated
      with an average size of 1.5 cm +/- 0.5 cm. Median follow-up was 6 months. Three
      incomplete ablations account for 21% (3/14), 2 of them occurring in 2 metastases
      larger than 2 cm percutaneously treated with 5 needles instead of 4 used for
      smaller tumor sizes. CONCLUSION: IRE was introduced without difficulties into
      clinical practice. As a main obstacle emerged in visualization of the needles,
      computed tomography may offer advantages in the guidance of percutaneous IRE of
      liver metastases larger than 2 cm. Local failure occurred in 21%.

PMID- 25598988
TI  - Pediatric myocarditis: A sentinel of non-cardiac chronic diseases?
AB  - INTRODUCTION: Although long-term outcome studies in large pediatric
      myocarditis/cardiomyopathy populations have been reported in literature, none of
      them focused on comorbidities. METHODS: All children and adolescents (age <18
      years) treated with myocarditis at the Department of Pediatrics, University of
      Debrecen, Hungary were followed. Patients suffering from myocarditis during the
      period 1996-2011 were enrolled. RESULTS: Over the 16-year period, a diagnosis of
      myocarditis was established in nine children. Their median age was 1.11 (0.03
      8.71) years. Three of the nine patients died. Left ventricular dilatation and
      ejection fraction normalized within 1-21 months in the survivors. None of the
      cases progressed to dilated cardiomyopathy. Regarding non-cardiac comorbidities,
      myocarditis or recurrent peri-myocarditis preceded the manifestation of celiac
      disease in two patients, while cystic fibrosis was diagnosed after the
      improvement of cardiac function in another, and Alstrom syndrome was diagnosed
      several years after complete recovery from myocarditis in yet another patient.
      CONCLUSION: These results suggest that manifestations of other chronic pediatric
      diseases may be more frequent among survivors of pediatric myocarditis. Prolonged
      follow-up of patients who survive myocarditis is therefore recommended not only
      to detect possible progression to cardiomyopathy but also to identify non-cardiac
      comorbidities.

PMID- 25598986
TI  - Curcumin a potent cancer preventive agent: Mechanisms of cancer cell killing.
AB  - There is no doubt that diet could effectively improve health and halt cancers.
      Dietary phytochemical compounds and their derivatives represent a cornucopia of
      effectively anticancer compounds. This review discusses existing data on the
      anticancer activities of curcumin, and then offers possible explanations for and
      mechanisms of its cancer-preventive action. This review also offers insights into
      the molecular mechanism and targets through which curcumin modulates cell cycle,
      apoptotic signals, anti-apoptotic proteins, miRNAs, Wnt/beta-catenin signaling,
      protein kinases, nuclear factor-kappaB, proteasome activation, epigenetic
      regulation including DNA methylation and histone modification. Finally, this
      review provides explanations for how curcumin reverses the multi-drug resistance
      (MDR) of cancer cells. 

PMID- 25598990
TI  - Blood pressure responses to resistive exercise in trained female athletes:
      Influence of velocity of movement.
AB  - The purpose of this study was to examine post-exercise hypotension (PEH)
      responses to three different resistance exercise velocities in female athletes.
      The 13 female subjects with experience of resistance training performed a series
      of resistance exercises with 80% of one repetition maximum for 3 sets with
      differing in velocity of movements: fast movement (FM; 1-second eccentric and 1
      second concentric actions), moderate movement (MM; 1-second eccentric and 2
      second concentric actions) and slow movement (SM; 2-second eccentric and 4-second
      concentric actions). After completing each training session, systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) were taken every 10 min for a
      period of 60 min of recovery. The results indicated significant increases in SBP
      at 10th min post-exercise in comparison to baseline. After 60-min recovery, all
      conditions showed statistically significant decreases in SBP when compared with
      pre-exercise. In all measured moments, there were no significant differences
      among experimental sessions in post-exercise levels of SBP and DBP. Therefore,
      resistance training with FM, MM, and SM can induce increases in SBP after
      exercise, whereas after 60-min recovery, can induce decreases in SBP or post
      exercise hypotension. 

PMID- 25598989
TI  - Impact of the insulin and glucose content of the postoperative fluid on the
      outcome after pediatric cardiac surgery.
AB  - INTRODUCTION: The aim of this study was to investigate the role of the insulin
      and glucose content of the maintenance fluid in influencing the outcomes of
      pediatric patients undergoing heart surgery. METHODS: A total of 2063 consecutive
      pediatric patients undergoing cardiac surgery were screened between 2003 and
      2008. A dextrose and an insulin propensity-matched group were constructed. In the
      dextrose model, 5% and 10% dextrose maintenance infusions were compared below 20
      kg of weight. RESULTS: A total of 171 and 298 pairs of patients were matched in
      the insulin and glucose model, respectively. Mortality was lower in the insulin
      group (12.9% vs. 7%, p = 0.049). The insulin group had longer intensive care unit
      (ICU) stay [days, 10.9 (5.8-18.4) vs. 13.7 (8.2-21), p = 0.003], hospital stay
      [days, 19.8 (13.6-26.6) vs. 22.7 (17.6-29.7), p < 0.01], duration of mechanical
      ventilation [hours, 67 (19-140) vs. 107 (45-176), p = 0.006], and the incidence
      of severe infections (18.1% vs. 28.7%, p = 0.01) and dialysis (11.7% vs. 24%, p =
      0.001) was higher. In the dextrose model, the incidence of pulmonary
      complications (13.09% vs. 22.5%, p < 0.01), low cardiac output (17.11% vs. 30.9%,
      p < 0.01), and severe infections (10.07% vs. 20.5%, p < 0.01) was higher, and the
      duration of the hospital stay [days, 16.4 (13.1-21.6) vs. 18.1 (13.8-24.6), p <
      0.01] was longer in the 10% dextrose group. CONCLUSIONS: Insulin treatment
      appeared to decrease mortality, and lower glucose content was associated with
      lower occurrence of adverse events.

PMID- 25598991
TI  - Bedside lung ultrasound versus chest X-ray use in the emergency department.
AB  - Acute dyspnoea is one of the most common reasons patients present to the
      emergency departments (ED). In most cases, the physical examination and bedside
      radiographs are inconclusive, resulting in the need for more sophisticated
      diagnostics. These diagnostics may delay treatment or expose the patient to
      unnecessary radiation. Here, we present the case of a dyspnoeic patient with a
      normal chest X-ray. The patient was diagnosed with pneumonia by bedside lung
      ultrasound (BLUS). BLUS revealed bilateral pleural effusion, which was more
      significant on the right side of the thorax. The right lower lung lobe was
      consolidated and quad, sinusoid and shred signs were present on BLUS. Chest X
      rays demonstrated normal findings. Based on this discrepancy, computerised
      tomography (CT) of the chest was ordered. A consolidated right lower lung lobe
      was clearly appreciated with bilateral pleural effusion. However, this finding
      was not observed on the chest X-ray. Because of the dynamic nature of the disease
      process, we were able to diagnose pathological changes in the lung earlier with
      the use of BLUS. In conclusion, this modality may replace the chest X-ray in the
      ED because it can be used bedside, has high accuracy, and minimal cost. 

PMID- 25598992
TI  - Coronary vasomotion dysfunction after everolimus-eluting stent implantation.
AB  - First generation drug-eluting stent can cause a paradoxical "in-segment" coronary
      vasoconstriction. This phenomenon was seen with sirolimus, paclitaxel, and, more
      recently, also with zotarolimus-eluting stent. For the first time, we describe a
      case of coronary-induced vasoconstriction by everolimus-eluting stents (EES). 

PMID- 25598993
TI  - Coronary spasm during cardiac electrophysiological study following isoproterenol
      infusion.
AB  - Sudden cardiac death (SCD) remains the leading cause of death in industrialized
      world. The majority of SCD is caused by ventricular fibrillation associated with
      structural and/or ischemic heart disease. Ventricular fibrillation represents the
      final common pathway for SCD and, thus, is an attractive target for ablation.
      According to class I recommendation level of evidence A, an implantable
      cardioverter defibrillator (ICD) should be implanted for such patients [1]. Other
      than programmed electrical extrastimulus technique, isoproterenol infusion is
      commonly used in invasive cardiac electrophysiology labs for arrhythmia
      induction. We hereby report a rare case of transient coronary spasm during
      isoproterenol infusion for ventricular tachycardia induction testing. 

PMID- 25598994
TI  - Giant appendix or an appendiceal mucocele? Case report of an 11-year-old child.
AB  - We present an 11-year-old male child with an enormous appendix that was regarded
      as an appendiceal mucocele. The disorder is very rare and usually appears in
      middle aged patients. It is a clinical diagnosis. It could cause a variety of
      symptoms, especially, acute appendicitis and unidentified lesion in the right
      iliac fossa. According to the reasons, it could be just a curiosity without any
      relevancy or the sign of a malignant lesion with bad prognostic factors. The
      histopathological findings prove the origin. 

PMID- 25598996
TI  - Intramedullary osteosarcoma of the mandible: a clinicoradiologic perspective.
AB  - Osteosarcoma is a non-hematopoietic primary malignant tumor of bone or
      mesenchymal tissue. Although osteosarcoma is not a common malignant bone tumor,
      accounting for approximately 20% of sarcomas, tumor of the jaw bone is uncommon,
      representing only about 4% of osteosarcomas of long bones. We report a case of a
      72-year-old female with a swelling on the left side of the mandible and intra
      oral swelling on the floor of the mouth. Conventional radiograph and advanced
      imaging modalities such as computed tomography and magnetic resonance imaging
      revealed an intramedullary osteosarcoma of the mandible. This report highlights
      importance of imaging modalities in the diagnosis of malignant tumors of the
      jaws. 

PMID- 25598998
TI  - Summary of Recommendation Statements.

PMID- 25598997
TI  - Chapter 7: Blood pressure management in elderly persons with CKD ND.

PMID- 25598995
TI  - Association between inflammatory markers and liver fat: The Multi-Ethnic Study of
      Atherosclerosis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common liver disease.
      Data is emerging that an independent association between markers of subclinical
      atherosclerosis and NAFLD exists and it may be considered as an independent
      predictor of cardiovascular (CV) outcomes. We aim to better characterize the
      relationship between NAFLD and inflammatory markers in a multi-ethnic cohort by
      assessing fatty liver on computed tomography (CT) scans. METHODS: The Multi
      Ethnic Study of Atherosclerosis (MESA) is a longitudinal, population-based study
      from four ethnic groups free of CV disease at baseline. The inflammatory markers
      studied include: C-reactive protein (CRP) and interleukin 6 (IL-6). On CT scans
      liver-to-spleen ratio (LSR: Hounsfield Units (HU) of the liver divided by HU of
      spleen) of <1 and liver attenuation of <40 HU were used as criteria for fatty
      liver. Unadjusted and adjusted multivariate linear and logistic regression
      analysis was performed. RESULTS: 4038 participants amongst 6814 MESA population
      with visible spleen on the CT scan, available CRP and IL-6 levels and no reported
      liver cirrhosis were included. The average age was 61 +/- 10 years, 37%
      Caucasians and 45% were males. Mean CRP and IL-6 were 2.36 mg/dl and 1.37 pg/ml
      respectively. 696 participants (17%) had LSR of <1 and 253 (6%) had liver
      attenuation of <40 HU. When using LSR <1 as a continuous variable, the
      correlation (adjusted odds ratio (OR)) with CRP >2.0 was 0.037 (95% CI: 0.02
      0.054) and with IL-6 was 0.014 (95% CI: 0.004-0.023). On the other hand when
      presence and absence of LSR <1 was considered, higher ORs for association with
      CRP >2: 1.41 (95% CI: 1.16 to 1.73) and IL6:1.18 (95% CI: 1.05 to 1.31) were
      found. Similarly, the adjusted association of per unit decrease in liver
      attenuation with CRP>2 was 1.92 (95% CI: 1.20 to 2.63) while for IL-6 was 1.08
      (95% CI: 0.69 to 1.47). When considering presence and absence of liver
      attenuation <40 HU the OR for CRP >2 was 2.27 (95% CI: 1.62 to 3.16) and for IL-6
      was 1.33 (95% CI: 1.13 to 1.58). CONCLUSION: CRP and IL-6 levels were found to be
      significantly associated with liver fat assessed on CT scan after adjusting for
      other risk factors for atherosclerosis.

PMID- 25598999
TI  - Chapter 3: Management of progression and complications of CKD.

PMID- 25599003
TI  - Retaining Participants in Outpatient and Community-Based Health Studies:
      Researchers and Participants in Their Own Words.
AB  - Loss to follow-up can introduce bias into research, making it difficult to
      develop inclusive evidence-based health policies and practice guidelines. We
      aimed to deepen understanding of reasons why participants leave or remain in
      longitudinal health studies. We interviewed 59 researchers and current and former
      research participants in six focus groups (n = 55) or interviews (n = 4) at three
      study centers in a large academic research institution. We used minimally
      structured interview guides and inductive thematic analysis to explore
      participant-level, study-level, and contextual participation barriers and
      facilitators. Four main themes emerged: transportation, incentives and
      motivation, caregiver concerns, and the social and physical environment. Themes
      shared crosscutting issues involving funding, flexibility, and relationships
      between researchers and research participants. Study-level and contextual factors
      appear to interact with participant characteristics, particularly socioeconomic
      status and disease severity to affect participant retention. Participants'
      characteristics do not seem to be the main cause of study dropout. Researchers
      and funders might be able to address contextual and study factors in ways that
      reduce barriers to participation.

PMID- 25599000
TI  - Chapter 4: Other complications of CKD: CVD, medication dosage, patient safety,
      infections, hospitalizations, and caveats for investigating complications of CKD.

PMID- 25599002
TI  - Application of Umbilical Cord Blood Derived Stem Cells in Diseases of the Nervous
      System.
AB  - Umbilical cord blood (UCB) derived multipotent stem cells are capable of giving
      rise hematopoietic, epithelial, endothelial and neural progenitor cells. Thus
      suggested to significantly improve graft-versus-host disease and represent the
      distinctive therapeutic option for several malignant and non-malignant diseases.
      Recent advances in strategies to isolate, expand and shorten the timing of UCB
      stem cells engraftment have tremendously improved the efficacy of
      transplantations. Nervous system has limited regenerative potential in disease
      conditions such as cancer, neurodegeneration, stroke, and several neural
      injuries. This review focuses on application of UCB derived stem/progenitor cells
      in aforementioned pathological conditions. We have discussed the possible
      attempts to make use of UCB therapies to generate neural cells and tissues with
      developmental and functional similarities to neuronal cells. In addition,
      emerging applications of UCB derived AC133+ (CD133+) endothelial progenitor cells
      (EPCs) as imaging probe, regenerative agent, and gene delivery vehicle are
      mentioned that will further improve the understanding of use of UCB cells in
      therapeutic modalities. However, safe and effective protocols for cell
      transplantations are still required for therapeutic efficacy.

PMID- 25599004
TI  - The Roles of Small GTPases in Osteoclast Biology.
AB  - The adult skeleton undergoes bone remodeling that consists of bone formation by
      osteoblasts and bone resorption by osteoclasts. When the amount of bone resorbed
      is greater than the amount of new bone formed, low bone mass results, putting
      individuals at increased risk for osteoporosis and osteoporotic bone fracture.
      Nitrogenous bisphosphonates (NBPs) are the most common first line treatment for
      conditions of low bone mass. NBPs reduce osteoclast bone resorption by impairing
      the post-translational modification of small GTPases. Small GTPases play crucial
      roles in the differentiation, function, and survival of osteoclasts.
      Understanding the roles of individual small GTPases in osteoclast biology may
      lead to more targeted therapies for the treatment of low bone mass. In this
      review, we discuss recent investigations into the in vivo effects of individual
      GTPase deletion in osteoclasts and the molecular roles for small GTPases in
      osteoclast biology.

PMID- 25599005
TI  - Current Protocols in Mouse Biology.
AB  - Bone is an essential organ that not only confers structural stability to the
      organism, but also serves as a reservoir for hematopoietic elements and is
      thought to affect systemic homeostasis through the release of endocrine factors
      as well as calcium. The loss of bone mass due to an uncoupling of bone formation
      and bone resorption leads to increased fragility that can result in devastating
      fractures. Further understanding of the effects of environmental stimuli on the
      development of bone disease in humans is needed, and can be studied using animal
      models. In this chapter, we present established and novel methods for the
      induction of bone loss in mice, including manipulation of diet and environment,
      drug administration, irradiation, and hormone deficiency. All of these models are
      directly related to human cases, and can thus be used to investigate the causes
      of bone loss resulting from these interventions.

PMID- 25599006
TI  - DASH and Mediterranean-type Dietary Patterns to Maintain Cognitive Health.
AB  - There is growing consensus that as the US population ages, nearly a third will
      experience stroke, dementia or even both. Thus, interest in the role that diet
      may play in preserving cognitive abilities continues to grow especially in
      absence of truly effective treatments for dementia, of which Alzheimer's disease
      (AD) is the most common form. The purpose of this review is to examine whether
      two a priori dietary patterns influence the rate of cognitive decline or the
      onset of dementia. Evidence from neuropathology reports of those who have died
      with AD or with mild cognitive impairment (MCI) or without cognitive impairment
      suggests that often the pathological hallmarks of AD---amyloid deposition and
      presence of tangles are present along with vascular lesions. Hypertension and
      stroke are strongly associated with incident dementia. Thus, it is possible that
      lifestyle approaches designed to prevent or reduce cardiovascular risk factors,
      conditions or diseases may also provide added benefits for brain health.

PMID- 25599008
TI  - Physical Activity, Mediterranean Diet and Biomarkers-Assessed Risk of
      Alzheimer's: A Multi-Modality Brain Imaging Study.
AB  - : Increased physical activity and higher adherence to a Mediterranean-type diet
      (MeDi) have been independently associated with reduced risk of Alzheimer's
      disease (AD). Their association has not been investigated with the use of
      biomarkers. This study examines whether, among cognitively normal (NL)
      individuals, those who are less physically active and show lower MeDi adherence
      have brain biomarker abnormalities consistent with AD. METHODS: Forty-five NL
      individuals (age 54 +/- 11, 71% women) with complete leisure time physical
      activity (LTA), dietary information, and cross-sectional 3D T1-weigthed MRI, 11C
      Pittsburgh Compound B (PiB) and 18F-fluorodeoxyglucose (FDG) Positron Emission
      Tomography (PET) scans were examined. Voxel-wise multivariate partial least
      square (PLS) regression was used to examine the effects of LTA, MeDi and their
      interaction on brain biomarkers. Age, gender, ethnicity, education, caloric
      intake, BMI, family history of AD, Apolipoprotein E (APOE) genotype, presence of
      hypertension and insulin resistance were examined as confounds. Subjects were
      dichotomized into more and less physically active (LTA+ vs. LTA-; n = 21 vs. 24),
      and into higher vs. lower MeDi adherence groups (n = 18 vs. 27) using published
      scoring methods. Spatial patterns of brain biomarkers that represented the
      optimal association between the images and the groups were generated for all
      modalities using voxel-wise multivariate Partial Least Squares (PLS) regression.
      RESULTS: Groups were comparable for clinical and neuropsychological measures.
      Independent effects of LTA and MeDi factors were observed in AD-vulnerable brain
      regions for all modalities (p < 0.001). Increased AD-burden (in particular higher
      Abeta load and lower glucose metabolism) were observed in LTA- compared to LTA+
      subjects, and in MeDi- as compared to MeDi+ subjects. A gradient effect was
      observed for all modalities so that LTA-/MeDi- subjects had the highest and
      LTA+/MeDi+ subjects had the lowest AD-burden (p < 0.001), although the LTA * MeDi
      interaction was significant only for FDG measures (p < 0.03). Adjusting for
      covariates did not attenuate these relationships. CONCLUSION: Lower physical
      activity and MeDi adherence were associated with increased brain AD-burden among
      NL individuals, indicating that lifestyle factors may modulate AD risk. Studies
      with larger samples and longitudinal evaluations are needed to determine the
      predictive power of the observed associations.

PMID- 25599011
TI  - Radiolabeled antibodies for therapy of infectious diseases.
AB  - Novel approaches to treatment of infectious diseases are urgently needed. This
      need has resulted in renewing the interest in antibodies for therapy of
      infectious diseases. Radioimmunotherapy (RIT) is a cancer treatment modality,
      which utilizes radiolabeled monoclonal antibodies (mAbs). During the last decade
      we have translated RIT into the field of experimental fungal, bacterial and HIV
      infections. In addition, successful proof of principle experiments with
      radiolabeled pan-antibodies that bind to antigens shared by major pathogenic
      fungi were performed in vitro. The armamentarium of pan-antibodies would result
      in reducing the dependence on microorganism-specific antibodies and thus would
      speed up the development of RIT of infections. We believe that the time is ripe
      for deploying RIT into the clinic to combat infectious diseases.

PMID- 25599007
TI  - Diet, lifestyle, and genetic risk factors for type 2 diabetes: a review from the
      Nurses' Health Study, Nurses' Health Study 2, and Health Professionals' Follow-up
      Study.
AB  - The epidemiological evidence collected from three large US cohorts (Nurses'
      Health Study, Nurses' Health Study 2, and Health Professionals' Follow-up Study)
      has yielded important information regarding the roles of overall diet, individual
      foods and nutrients, physical activity and other lifestyle factors in the
      development of type 2 diabetes. Excess adiposity is a major risk factor for
      diabetes, and thus, maintaining a healthy body weight and avoidance of weight
      gain during adulthood is the cornerstone of diabetes prevention. Independent of
      body weight, the quality or type of dietary fat and carbohydrate is more crucial
      than the quantity in determining diabetes risk. Higher consumption of coffee,
      whole grains, fruits, and nuts is associated with lower risk of diabetes, whereas
      regular consumption of refined grains, red and processed meats, and sugar
      sweetened beverages including fruits juices is associated with increased risk.
      Dietary patterns rich in fruits and vegetables, whole grains, and nuts and
      legumes but lower in red and processed meats, refined grains, and sugar-sweetened
      beverages are consistently associated with diabetes risk, even after adjustment
      for body mass index. The genome-wide association studies conducted in these
      cohorts have contributed substantially to the discoveries of novel genetic loci
      for type 2 diabetes and other metabolic traits, although the identified common
      variants explain only a small proportion of overall diabetes predisposition.
      Taken together, these ongoing large cohort studies have provided convincing
      epidemiologic evidence that a healthy diet, together with regular physical
      activity, maintenance of a healthy weight, moderate alcohol consumption, and
      avoidance of sedentary behaviors and smoking would prevent the majority of type 2
      diabetes cases.

PMID- 25599010
TI  - Direct Blood Flow Measurements in a Free RPE-Choroid Graft with Phase-Resolved
      Doppler OCT.
AB  - PURPOSE: We directly demonstrated the revascularization in a free retinal pigment
      epithelium (RPE)-choroid graft with direct blood flow detection by experimental
      phase-resolved Doppler optical coherence tomography (PRD-OCT). METHODS: Seven
      patients with age-related macular degeneration underwent an RPE-choroid graft
      translocation in a prospective institutional cohort study. Spectral domain
      optical coherence tomography (SD-OCT) was used to measure the revascularization
      stage. With PRD-OCT the presence of flow was imaged postoperatively. RESULTS: The
      PRD-OCT confirmed flow in three patients when SD-OCT indicated the afferent
      vessel ingrowth stage, and in all seven patients when the SD-OCT indicated the
      efferent vessel ingrowth stage. CONCLUSIONS: The PRD-OCT study was able to detect
      the presence of blood flow in a free RPE-choroid graft. The PRD-OCT findings
      directly confirmed the revascularization that was otherwise based on the more
      circumstantial evidence provided by SD-OCT images and angiography. TRANSLATIONAL
      RELEVANCE: The use of both techniques to monitor the revascularization process in
      a free graft in patients are an interesting example of replacing more invasive by
      noninvasive techniques. There is potential future use of PRD-OCT for the
      visualization of vascularization patterns in other pathologies.

PMID- 25599012
TI  - Falling Short of Guidelines? Nutrition and Weight Gain Knowledge in Pregnancy.
AB  - OBJECTIVES: The objective of this study was to characterize pregnant women's
      gestational weight gain (GWG) knowledge and awareness of healthy eating behaviors
      known to impact GWG. METHODS: Formative research was conducted including semi
      structured individual interviews and focus group interviews. The participants
      were mostly Caucasian pregnant women (N = 30; Mage = 28 years old) residing in a
      suburban/rural region of Central Pennsylvania. Descriptive and thematic analyses
      were used to examine the primary outcomes of GWG and healthy eating knowledge and
      informational sources. RESULTS: Many women had no knowledge of how much GWG they
      should gain in pregnancy (42%). Women appeared to have adequate knowledge on
      foods they should avoid eating during pregnancy. However, one-fourth of women
      indicated that they did not feel as though they received adequate information
      from their healthcare provider about the foods they should be eating and how to
      meet the healthy eating recommendations. Therefore, one-fourth of women reported
      using non-healthcare provider resources (e.g., magazines, internet) with
      questionable reliability to obtain healthy eating guidance. CONCLUSION: These
      exploratory findings show that pregnant women have some knowledge of the GWG and
      healthy eating guidelines; however, most women received this information from a
      non-healthcare provider resource. Focused efforts are needed to educate pregnant
      women about GWG and healthy eating using accurate and reliable sources
      andencourage strategies to meet guidelines in an effort to promote healthy GWG.

PMID- 25599013
TI  - Portal Fibroblasts in Biliary Fibrosis.
AB  - Portal fibroblasts are a minor population in the normal liver, found in the
      periportal mesenchyme surrounding the bile ducts. While many researchers have
      hypothesized that they are an important myofibroblast precursor population in
      biliary fibrosis, responsible for matrix deposition in early fibrosis and for
      recruiting hepatic stellate cells, the role of portal fibroblasts relative to
      hepatic stellate cells is controversial. Several papers published in the past
      year have addressed this point and have identified other potential roles for
      portal fibroblasts in biliary fibrosis. The goal of this review is to critically
      assess these recent studies, to highlight gaps in our knowledge of portal
      fibroblasts, and to suggest directions for future research.

PMID- 25599009
TI  - Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure.
AB  - PURPOSE: We examined the efficacy of an extended-release drug delivery system,
      nanosponge (NS) encapsulated compounds, administered intravitreally to lower
      intraocular pressure (IOP) in mice. METHODS: Bilateral ocular hypertension was
      induced in mice by injecting microbeads into the anterior chamber. Hypertensive
      mice received NS loaded with ocular hypotensive drugs via intravitreal injection
      and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake
      of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using
      confocal microscopy. RESULTS: Brimonidine-loaded NS lowered IOP 12% to 30% for up
      to 6 days (P < 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4
      days (P < 0.02) compared to saline injection. Three bimatoprost NS were tested: a
      400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC
      NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up
      to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and
      18% to 26%, respectively, for up to 32 days (P < 0.046). Over time retinal
      deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was
      internalized by RGCs. CONCLUSIONS: A single injection of NS can effectively
      deliver ocular hypotensive drugs in a linear and continuous manner for up to 32
      days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in
      glaucoma. TRANSLATIONAL RELEVANCE: Patient compliance is a major issue in
      glaucoma. The use of NS to deliver a controlled, sustained release of
      therapeutics could drastically reduce the number of patients that progress to
      vision loss in this disease.

PMID- 25599001
TI  - Chapter 5: Referral to specialists and models of care.

PMID- 25599014
TI  - Synthesis, Physicochemical Studies, Molecular Dynamics Simulations, and Metal-Ion
      Dependent Antiproliferative and Antiangiogenic Properties of Cone ICL670
      Substituted Calix[4]arenes.
AB  - Iron chelators, through their capacity to modulate the iron concentration in
      cells, are promising molecules for cancer chemotherapy. Chelators with high
      lipophilicity easily enter into cells and deplete the iron intracellular pool.
      Consequently, iron-dependent enzymes, such as ribonucleotide reductase, which is
      over-expressed in cancer cells, become nonfunctional. A series of calix[4]arene
      derivatives substituted at the lower rim by ICL670, a strong FeIII chelator, have
      been synthesized. Physicochemical properties and antiproliferative, angiogenesis,
      and tumorigenesis effects of two calix[4]arenes mono- (5a) or disubstituted (5b)
      with ICL670 have been studied. These compounds form metal complexes in a ratio of
      one to two ligands per FeIII atom as shown by combined analyses of the
      protometric titration curves and ESIMS spectra. The grafting of an ICL670 group
      on a calix[4]arene core does not significantly alter the acid-base properties,
      but improves the iron-chelating and lipophilicity properties. The best
      antiproliferative and anti-angiogenic results were obtained with calix[4]arene
      ligand 5a, which possesses the highest corresponding properties. Analyses of
      molecular dynamics simulations performed on the two calix[4]arenes provide three
      dimensional structures of the complexes and proved 5a to be the most stable upon
      complexation.

PMID- 25599015
TI  - Techniques for fluorescence detection of protoporphyrin IX in skin cancers
      associated with photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a treatment modality that uses a specific
      photosensitizing agent, molecular oxygen, and light of a particular wavelength to
      kill cells targeted by the therapy. Topically administered aminolevulinic acid
      (ALA) is widely used to effectively treat cancerous and precancerous skin
      lesions, resulting in targeted tissue damage and little to no scarring. The
      targeting aspect of the treatment arises from the fact that ALA is preferentially
      converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the
      amount of PpIX in tissues, techniques have been developed to measure PpIX
      specific fluorescence, which provides information useful for monitoring the
      abundance and location of the photosensitizer before and during the illumination
      phase of PDT. This review summarizes the current state of these fluorescence
      detection techniques. Non-invasive devices are available for point measurements,
      or for wide-field optical imaging, to enable monitoring of PpIX in superficial
      tissues. To gain access to information at greater tissue depths, multi-modal
      techniques are being developed which combine fluorescent measurements with
      ultrasound or optical coherence tomography, or with microscopic techniques such
      as confocal or multiphoton approaches. The tools available at present, and newer
      devices under development, offer the promise of better enabling clinicians to
      inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes
      for patients.

PMID- 25599016
TI  - A television in the bedroom is associated with higher weekday screen time among
      youth with attention deficit hyperactivity disorder (ADD/ADHD).
AB  - OBJECTIVE: A TV in the bedroom has been associated with screen time in youth.
      Youth with attention deficit hyperactivity disorder (ADD/ADHD) have higher rates
      of screen time, but associations with bedroom TVs are unknown in this population.
      We examined the association of having a bedroom TV with screen time among youth
      with ADD/ADHD. METHODS: Data were from the 2007 National Survey of Children's
      Health. Youth 6-17 years whose parent/guardian reported a physician's diagnosis
      of ADD/ADHD (n = 7,024) were included in the analysis. Parents/guardians reported
      the presence of a bedroom TV and average weekday TV screen time. Multivariate
      linear and logistic regression models assessed the effects of a bedroom on screen
      time. RESULTS: Youth with ADD/ADHD engaged in screen time an average of 149.1
      minutes/weekday and 59% had a TV in their bedroom. Adjusting for child and family
      characteristics, having a TV in the bedroom was associated with 25 minutes higher
      daily screen time (95% CI: 12.8-37.4 min/day). A bedroom TV was associated with
      32% higher odds of engaging in screen time for over 2 hours/day (OR=1.3; 95% CI:
      1.0-1.7). CONCLUSION: Future research should explore whether removing TVs from
      bedrooms reduces screen time among youth with ADD/ADHD.

PMID- 25599017
TI  - A Growing Opportunity: Community Gardens Affiliated with US Hospitals and
      Academic Health Centers.
AB  - BACKGROUND: Community gardens can reduce public health disparities through
      promoting physical activity and healthy eating, growing food for underserved
      populations, and accelerating healing from injury or disease. Despite their
      potential to contribute to comprehensive patient care, no prior studies have
      investigated the prevalence of community gardens affiliated with US healthcare
      institutions, and the demographic characteristics of communities served by these
      gardens. METHODS: In 2013, national community garden databases, scientific
      abstracts, and public search engines (e.g., Google Scholar) were used to identify
      gardens. Outcomes included the prevalence of hospital-based community gardens by
      US regions, and demographic characteristics (age, race/ethnicity, education,
      household income, and obesity rates) of communities served by gardens. RESULTS:
      There were 110 healthcare-based gardens, with 39 in the Midwest, 25 in the South,
      24 in the Northeast, and 22 in the West. Compared to US population averages,
      communities served by healthcare-based gardens had similar demographic
      characteristics, but significantly lower rates of obesity (27% versus 34%, p <
      .001). CONCLUSIONS: Healthcare-based gardens are located in regions that are
      demographically representative of the US population, and are associated with
      lower rates of obesity in communities they serve.

PMID- 25599019
TI  - Exploration of the use of Bayesian modeling of gradients for censored
      spatiotemporal data from the Deepwater Horizon oil spill.
AB  - This paper develops a hierarchical framework for identifying spatiotemporal
      patterns in data with a high degree of censoring using the gradient process. To
      do this, we impute censored values using a sampling-based inverse CDF method
      within our Markov chain Monte Carlo algorithm, thereby avoiding burdensome
      integration and facilitating efficient estimation of other model parameters. We
      illustrate use of our methodology using a simulated data example, and uncover the
      danger of simply substituting a space- and time-constant function of the level of
      detection for all missing values. We then fit our model to area measurement data
      of volatile organic compounds (VOC) air concentrations collected on vessels
      supporting the response and clean-up efforts of the Deepwater Horizon oil release
      that occurred starting April 20, 2010. These data contained a high percentage of
      observations below the detectable limits of the measuring instrument. Despite
      this, we were still able to make some interesting discoveries, including elevated
      levels of VOC near the site of the oil well on June 26th. Using the results from
      this preliminary analysis, we hope to inform future research on the Deepwater
      Horizon study, including the use of gradient methods for assigning workers to
      exposure categories.

PMID- 25599018
TI  - Human Cardiac Tissue Engineering: From Pluripotent Stem Cells to Heart Repair.
AB  - Engineered cardiac tissues hold great promise for use in drug and toxicology
      screening, in vitro studies of human physiology and disease, and as
      transplantable tissue grafts for myocardial repair. In this review, we discuss
      recent progress in cell-based therapy and functional tissue engineering using
      pluripotent stem cell-derived cardiomyocytes and we describe methods for delivery
      of cells into the injured heart. While significant hurdles remain, notable
      advances have been made in the methods to derive large numbers of pure human
      cardiomyocytes, mature their phenotype, and produce and implant functional
      cardiac tissues, bringing the field a step closer to widespread in vitro and in
      vivo applications.

PMID- 25599021
TI  - Molecular mechanisms involved in tumor repopulation after radiotherapy.
AB  - Radiotherapy remains one of most important treatment modalities for solid tumors.
      Current radiotherapy is mostly based on a set of concepts called the 4"R"s, which
      were established when there was lack of understanding of the underlying molecular
      mechanisms. However, progress made in the past two decades are beginning to allow
      us to see some of the molecular details involved in tumor response to radiation
      therapy. In this review, we will attempt to summarize some of the key discoveries
      in molecular radiation biology that have direct relevance to radiotherapy. We
      will focus our discussion on areas such as radiation induced tumor
      vasculogenesis, stem cell mobilization, and cellular repopulation. We hope our
      discussion will stimulate further studies in this important area of cancer
      research.

PMID- 25599020
TI  - Vitamin D Status, Receptor Gene Polymorphisms, and Supplementation on
      Tuberculosis: A Systematic Review of Case-Control Studies and Randomized
      Controlled Trials.
AB  - OBJECTIVE: To investigate the impacts of vitamin D status, supplementation and
      vitamin D receptor (VDR) gene polymorphisms on tuberculosis (TB). METHODS: We
      conducted a systematic review of published studies pertaining to case-control and
      randomized-control trials from 2002 to 2014 using the PubMed database. RESULTS
      AND CONCLUSION: Individuals with TB have lower vitamin D status than healthy
      individuals. Some VDR gene polymorphisms are associated with increased
      susceptibility to TB while others may not. Supplementation with vitamin D leads
      to improved clinical outcomes. However, further studies with a larger patient
      population and different ethnicities are needed to confirm these effects.

PMID- 25599023
TI  - Residual pneumoperitoneum volume and postlaparoscopic cholecystectomy pain.
AB  - BACKGROUND: Gasretention in the peritoneal cavity plays an important role in
      inducing postoperative pain after laparoscopy, which is inevitably retained in
      the peritoneal cavity. OBJECTIVES: The aim of this study was to detect the
      relation between the volume of residual gas and severity of shoulder and
      abdominal pain. PATIENTS AND METHODS: In this Prospective study 55 women who were
      referred for laparoscopic cholecystectomy, were evaluated for the effect of
      residual pneumoperitoneum on postlaparoscopic cholecystectomy pain intensity. The
      pneumoperitoneum was graded as absent, mild (1-5 mm), moderate (6-10 mm) and
      severe (> 11 mm). Patients were followed for postoperative abdominal and shoulder
      pain using visual analogue scale (VAS), postoperative analgesic requirements,
      presence of nausea and vomiting, time of unassisted ambulation, time of oral
      intake and time of return of bowel function in the recovery room and at 6, 12 and
      24 hours after operation. RESULTS: At the end of the study, 17 patients (30.9%)
      had no residual pneumoperitoneum after 24 hours; which 23 (41.81%) had mild
      residual pneumoperitoneum, eight (14.54%) had moderate pneumoperitoneum and seven
      (12.72%) had severe pneumoperitoneum. Patients with no or mild residual
      pneumoperitoneum had significantly lower abdominal and shoulder pain scores than
      whom with moderate to severe pneumoperitoneum (P = 0.00) and need less meperidine
      requirements (P = 0.00). Patients did not have any significant difference in time
      of oral intake, return of bowel function, nausea and vomiting percentages.
      CONCLUSIONS: We conclude that volume of residual pneumoperitoneum is a
      contributing factor in the etiology of postoperative pain after laparoscopic
      cholecystectomy.

PMID- 25599022
TI  - Attenuation of cisplathin-induced toxic oxidative stress by propofol.
AB  - BACKGROUND: Antioxidant effects of propofol (2, 6-diisopropylphenol) were
      evaluated against cisplatin-induced oxidative stress in rat. OBJECTIVES: In this
      experimental study, 20 male rats were equally divided into 4 groups (5 rats
      each), and were treated by propofol (10 mg/kg/day, IP), or cisplatin (7 mg
      /kg/day, IP), or both. MATERIALS AND METHODS: Group one was control, while group
      2 was given cisplatin (7 mg /kg/day, IP). Animals of the third group received
      only propofol (10 mg/kg/day, IP). Group 4 was given propofol with cisplatin once
      per day for 7 days. After treatment, blood urea nitrogen, creatinine levels, and
      oxidative stress markers such as total thiol groups (TTG), lipid peroxidation
      (LPO), and total antioxidant capacity (TAC) were measured. RESULTS: Oxidative
      stress induced by cisplatin, was evident by a significant increase in LPO and
      decrease in TTG and TAC. Propofol recovered cisplatin -induced changes in TAC,
      TTG and LPO in blood. CONCLUSIONS: It is concluded that oxidative damage is the
      mechanism of cisplatin toxicity, which can be recovered by propofol.

PMID- 25599024
TI  - Use of two Endotracheal Tubes to Perform Lung Isolation and One-Lung Ventilation
      in a Patient With Tracheostomy Stenosis: A Case Report.
AB  - INTRODUCTION: Lung isolation is a common technique used in thoracic surgery to
      prevent spillage to unaffected lung and to provide a better view for the surgeon.
      CASE PRESENTATION: A 41-year-old woman with a history of pharyngo-laryngo
      oesophagectomy (PLO) and tracheostomy was a candidate for thoracic duct ligation
      because of chylothorax. Since the patient had tracheostmy stomal stenosis, two
      cuffed tracheal tubes (internal diameter = 4.5 mm) were used; one tube was placed
      in the right bronchus and the other tube in the left one by fiberoptic
      laryngoscopy in 10 minutes. Right lung was collapsed during the surgery for 3.5
      hours with a slight decrease in oxygenation (SpO2 = 91%-93%) and with no evident
      hemodynamic change. Potential trauma from a double-lumen tube and a bronchial
      blocker as well as inaccessibility to a univent tube prevented us to use these
      standard methods in this case. CONCLUSIONS: This report presents a new method for
      lung isolation in specific cases and in the absence of certain equipment.

PMID- 25599025
TI  - Postoperative alterations in taste and smell.
AB  - CONTEXT: Alterations in taste and smell, including but not limited to anosmia,
      ageusia, hypogeusia, and dysgeusia, have been described in association with
      various medications, including anesthetic agents. Frequently, these symptoms
      occur 1-2 weeks after medication administration and last several months. While
      such a phenomenon is a rare occurrence, it nonetheless can significantly impact
      patients' satisfaction and quality of life. EVIDENCE ACQUISITION: The methodology
      consisted of a thorough literature search using the MEDLINE and Cochrane
      databases utilizing keywords such as anosmia, ageusia, olfactory disorders,
      postoperative, and anesthesia. RESULTS: Our results yielded several previously
      published case report, and were not limited to a specific type of anesthesia.
      Based on available literature, we review the physiology of taste and smell as
      well as the medications associated with loss of these senses. We describe
      perioperative agents that could lead to postoperative complications associated
      with anosmia and and ageusia. CONCLUSIONS: Based on available literature
      recommendations for anesthesiologists caring for patients at risk for this
      occurrence are presented in this review. The symptoms are usually temporary as in
      the majority of the patients the sensory receptor cells are able to regenerate
      themselves after injury. Anesthesia providers need to aware of this phenomenon to
      be able to reassure patients and possibly avoid anesthetic techniques associated
      with anosmia and ageusia.

PMID- 25599026
TI  - Can APACHE II Score Predict Diabetic Ketoacidosis in Hyperglycemic Patients
      Presenting to Emergency Department?
AB  - BACKGROUND: Diabetic ketoacidosis (DKA) is an acute and life-threatening
      complication in diabetic patients. The current diagnostic criteria of DKA are
      metabolic acidosis, blood glucose level greater than 250 mg/dL and the presence
      of ketones in serum or urine. DKA patients referring to the emergency department
      (ED) are usually ill. OBJECTIVES: The present study aims to evaluate the efficacy
      of Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring in
      predicting the critically illness in the hyperglycemic patients referring to the
      ED. PATIENTS AND METHODS: We performed a prospective cohort study in an ED. One
      hundred eighty one patients older than 18 years with hyperglycemia were included
      in our study. Following the primary evaluation, the subjects were divided into
      DKA and non-DKA patients. APACHE II scores were calculated for all patients and
      then compared to each other. We determined predictive value, sensitivity,
      specificity and cut-off points of APACHE II score for DKA. RESULTS: Sixty two
      patients had DKA. The comparison of APACHE II score among two groups of the
      patients did not show any significant difference (P = 0.597). There was no
      suitable cut-off point for APACHE II score to predict DKA. CONCLUSIONS: APACHE II
      score cannot be applied in the predicting of DKA in hyperglycemic patients
      admitted in ED.

PMID- 25599028
TI  - Drug recall: An incubus for pharmaceutical companies and most serious drug recall
      of history.
AB  - There has been an increasing trend in the number of prescribed and over-the
      counter drug recall over the last few years. The recall is usually due to
      company's discovery, customer's complaint or Food and Drug Administration (FDA)
      observation. The process of recall involves a planned specific course of action,
      which addresses the depth of recall, need for public warning, and the extent of
      effectiveness checks for the recall. The FDA review and/or recommend changes to
      the firm's recall strategy, as appropriate. The critical recall information list
      includes the identity of the product; summary of the failure; amount of product
      produced in the distribution chain and direct account. Product recalls clashes
      thousands of companies every year affecting: sales, testing customer
      relationships and disrupting supply chains. Drug recall is incubus for
      pharmaceutical companies. It effects the reputation of the company. The reason
      for the recall can be divided into two categories: manufacturing affined and
      safety/efficacy affined. It is essential to follow all the guidelines related to
      drug development and manufacturing procedure so as to minimize drug recall. 

PMID- 25599027
TI  - Role of excipients and polymeric advancements in preparation of floating drug
      delivery systems.
AB  - Since decade or two, the development of floating drug delivery systems becomes a
      significant and novel tool as having low density than gastric content. There are
      various advanced polymers including chitosan, eudragit, etc., and excipients such
      as; pore forming agent, surfactants, etc. All of them are discussed briefly, and
      results are concluded from various reputed researches. We have discussed all
      natural and synthetic systems with their effect on the release and other
      parameters which are essential for the floating formulation development. 

PMID- 25599029
TI  - Statistical modeling of zaltoprofen loaded biopolymeric nanoparticles:
      Characterization and anti-inflammatory activity of nanoparticles loaded gel.
AB  - OBJECTIVE: The main objective of this study is to formulate polymeric
      nanoparticles (NPs) loaded with zaltoprofen, an NSAID drug. The optimization, in
      terms of polymer concentration, stabilizer concentration and pH of the
      formulation was employed by 3-factor-3-level Box-Behnken experimental design.
      MATERIALS AND METHODS: The NPs of zaltoprofen were fabricated using chitosan and
      alginate as polymers by ionotropic gelation. The ionic interaction between the
      ionic polymers was studied using Fourier transform infrared and differential
      scanning calorimetry study. RESULT: For different formulation the average
      particle size ranged between 156 +/- 1.0 nm and 554 +/- 2.8 nm. The drug
      entrapment ranged between 61.40% +/- 3.20% and 90.20% +/- 2.47%. The ANOVA
      results exhibited that all the three factors were significant. The resultant
      optimized batch was characterized by particle size 156.04 +/- 1.4 nm, %entrapment
      efficacy 88.67% +/- 2.0%, zetapotential + 25.3 mV and polydispersity index 0.320.
      The scanning electron microscopy showed spherical NPs of average size 99.5 nm.
      The optimized NPs were loaded in carbopol gel, which was subjected to study of
      drug content, viscosity, spreadability, in vitro drug diffusion and in vivo
      antiinflammatory test on rats. CONCLUSION: This study showed that zaltoprofen NPs
      prepared using the ratio of polymer CS:AG:1:1.8, stabilizer concentration 0.98%
      and pH 4.73 was found to be of optimized particle size, maximum drug entrapment.
      The NPs loaded gel showed controlled release for 12 h following Korsmeryer-peppas
      model of the diffusion profile. The in vivo antiinflammatory study showed
      prolonged effect of NPs loaded gel for 10 h.

PMID- 25599031
TI  - Evaluation of the efficacy of 2% Ocimum sanctum gel in the treatment of
      experimental periodontitis.
AB  - INTRODUCTION: One of the options for the treatment of periodontitis is local drug
      delivery systems (LDD). Tulsi (Ocimum sanctum), a traditional herb, has many uses
      in medicine. It could be a suitable agent as LDD for the treatment of
      periodontitis. AIM: The aim was to formulate, evaluate the anti-inflammatory
      activity; assess duration of the action and the efficacy of 2% tulsi (O. sanctum)
      gel in the treatment of experimental periodontitis in Wistar Albino rat model.
      SETTINGS AND DESIGN: Thirty six Wistar albino rats were randomly assigned to 3
      groups. Periodontitis was induced using ligature model. Group 1-control; Group 2
      Plain gel and Group 3-2% tulsi (O. sanctum) gel. MATERIALS AND METHODS: 2% tulsi
      (O. sanctum) gel were prepared. The anti-inflammatory activity and duration of
      action were assessed. Silk ligature 5-0 was used to induce periodontitis.
      Gingival index (GI) and probing pocket depth were measured. Treatment was done.
      The rats were sacrificed. Morphometric analysis was done using Stereomicroscope
      and ImageJ software. STATISTICAL ANALYSIS USED: ANOVA followed by Bonferroni's
      test, Wilcoxon's test for intergroup comparison, Mann-Whitney test for P value
      computation was used. The observations are mean +/- standard deviation and
      standard error of the mean. P < 0.01 as compared to control was considered as
      statistically significant. RESULTS: 2% tulsi (O. sanctum) gel showed 33.66%
      inhibition of edema and peak activity was noted at 24 h. There was statistically
      significant change in the GI and probing pocket depth. Morphometric analysis did
      not show any significant difference between groups. No toxic effects were seen on
      oral administration of 2000 mg/kg of Tulsi extract. CONCLUSIONS: 2% tulsi (O.
      sanctum) gel was effective in the treatment of experimental periodontitis.

PMID- 25599032
TI  - Colon specific drug delivery of tramadol HCl for chronotherapeutics of arthritis.
AB  - OBJECTIVE: The objective of present work is to develop and evaluate a matrix
      system for Chronotherapeutic delivery of centrally acting of opioid analgesic
      (tramadol HCl) to treat nocturnal symptoms of arthritis using almond gum as
      carrier. MATERIALS AND METHODS: Matrix tablets of tramadol HCl were prepared by
      using 30, 40, 50, 60 and 70% w/w of tablet of gum badam as carrier by wet
      granulation technique. These tablets were compression coated with eudragit S100
      to prevent drug release in stomach. All formulations were evaluated for hardness,
      friability, weight variation, drug content, in vitro and in vivo studies. The
      almond gum was characterized by viscosity measurements and Fourier transform
      infrared analysis. The coated (FC1 to FC5) and uncoated tablets (F1 to F5) were
      evaluated for in vitro release of tramadol HCl after sequential exposure to pH
      1.2, pH 7.4 and pH 6.8 respectively for 2 h, 3 h and 19 h in the absence as well
      as presence of rat caecal content and the corresponding data was fitted to
      popular release kinetic equations in order to evaluate the release mechanisms
      kinetics. The selected formulation was subjected to in vivo targeting efficacy
      studies by roentgenography technique. RESULTS AND DISCUSSION: In vitro release
      studies indicated that the matrix tablets (F1 to F5) failed to control the drug
      release in the physiological environment of stomach and small intestine. On the
      other hand, compression coated formulations were able to protect the tablet cores
      from premature drug release. Presence of rat caecal content enhances the drug
      release from the tablets as the concentration of polymer increased, drug release
      was found to be retarded. The release of tramadol from all the formulation
      followed zero order with non fickian diffusion. X-ray studies confirmed that the
      tablet successfully reached colon without getting disintegrated in upper
      gastrointestinal tract. CONCLUSION: Based on the results, selective delivery of
      tramadol HCl to the colon could be achieved using 60% w/w (FC4) of almond gum
      matrix tablets compression coated with eudragit S100.

PMID- 25599030
TI  - Liposomal Aloe vera trans-emulgel drug delivery of naproxen and nimesulide: A
      study.
AB  - INTRODUCTION: The present aim of this study was to formulate naproxen and
      nimesulide liposomal formulation for incorporation in Aloe vera transemulgel and
      to carry out in vitro and in vivo evaluation of the formulation. MATERIAL AND
      METHODS: A. vera gel was prepared and used as a gel base for formulation.
      Carbopol 934 is used as a gelling agent and Methyl paraben was used as a
      preservative for the formulation of the gel. Liposomes was formulated by using
      hydration method. The formulated naproxen and nimesulide liposomal formulation
      using A. vera trans-emul gel were evaluated for in vitro studies such as drug
      release, permeation study, and drug content and entrapment efficiency. Paw edema
      method in Wistar rats induced by carrageenan is used to study in vivo anti
      inflammatory action. RESULT: From the in vitro studies such permeability drug
      release naproxen 65% (69.6), Nimesulide 65% (61.1), and commercial Nimsulide gel
      (60.82) at 240 min. In vivo data shows that formulated liposomal transemulgel
      formulation are superior in their efficacy compared to commercial and A. vera
      gel. The results are compared with the commercial formulations. CONCLUSION: From
      our results, it is concluded that the A. vera trans emul gel using nimesulide and
      naproxen liposomal formulation is stable and prepared gel base is effective for
      formulation with high drug release and drug content compared with commercial
      formulation with significant anti-inflammatory effect.

PMID- 25599033
TI  - Formulation and evaluation of clindamycin HCL in situ gel for vaginal
      application.
AB  - OBJECTIVE: The vagina has been studied as a favorable site for the local and
      systemic delivery of drugs, for female associated conditions. Vaginal
      preparations, although generally perceived as safer most still associated with
      number of problems including multiple days of dosing, dripping, leakage and
      messiness, causing discomfort to users and expulsion due to the self-cleansing
      action of the vaginal tract. These limitations lead to poor patient compliance
      and failure of the desired therapeutic effects. For efficient vaginal delivery of
      drugs, the delivery system should reside at the site of infection for a prolonged
      period of time. In situ gel formulation which combines advantages of both gels
      and solution so that an accurate dose can be administered with ease. These
      formulations remain in solution state before administration and transforms to gel
      after administration in to vaginal cavity. MATERIAL AND METHODS: In these
      formulations we prepared clindamycin loaded hydroxypropyl methycellulose (0.1%)
      (bioadhesive) and gellan gum (ion activated gelling polymer) based in situ gel
      system for vaginal application. NaCl (0.9%) was added as an isotonic agent. The
      developed formulation was characterized for various in vitro parameters such as
      clarity, refractive index, pH, viscosity, drug release profile, statistical
      release kinetics, bioadhesive force, and microbial efficacy along with stability
      studies. To simulate vaginal conditions, synthetic membrane (cellophane hydrated
      with modified simulated vaginal fluid) was used as model membranes. RESULTS AND
      DISCUSSION: The developed formulation was found to be nonirritant, bioadhesive
      with good retention properties. Formulations have satisfactory appearance,
      clarity and drug content in the range 98.1-101%. Refractive index of the gel is
      ranging from 1.335 to 1.337, proofing the transparency of gel. Furthermore,
      formulation displayed 33.3% cumulative drug release after 2 h. 67.4% after 6 h
      and 98.9% after 12 h. CONCLUSION: Developed formulation should be stable. Hence,
      formulation is thus a viable alternative to conventional vaginal dosage forms.

PMID- 25599034
TI  - In vitro and in vivo evaluation of fast-dissolving tablets containing solid
      dispersion of lamotrigine.
AB  - AIM: Investigation of in vitro/in vivo behavior of fast-dissolving tablets
      containing solid dispersions (SDs) of lamotrigine (LM) was the aim and focus of
      the present research work. MATERIAL AND METHODS: The effect of various
      hydrophilic polymers on the aqueous solubility of LM was studied. Polyethylene
      glycol (PEG 6000) was selected as the vehicle and SDs were prepared by melting
      and solvent evaporation method (SEM). Evaluation of SD for dissolution indicated
      SVM was more appropriate as seen from an enhancement in drug dissolution.
      Infrared spectroscopy, differential scanning calorimetry, and powder X-ray
      diffraction studies indicated a lack of physicochemical interaction between the
      drug and the carrier. A total of nine formulations were compressed into fast
      dissolving tablets using Avicel pH 102 as a directly compressible filler and ac
      di-sol, sodium starch glycolate and crospovidone as super disintegrates and
      evaluated for pre- and post-compression parameters and in vitro drug release.
      RESULTS: Mathematical analysis of in vitro data suggested that first order was
      most suitable mathematical model for describing the optimized formulation.
      Stability studies indicated that the effect of storage was insignificant at 5%
      level of confidence. In vivo studies of pure drug, selected formulation and
      marketed product were carried out in male Wistar rats and pharmacokinetic (PK)
      parameters were calculated using PK function for Microsoft Excel. The best
      formulation has shown Tmax of 0.5 h which was highly significant (P < 0.05) when
      compared with pure drug and marketed formulation. The statistical significance
      was assessed by one way analysis of variance. CONCLUSION: Therefore, the SDs
      prepared by SEM using PEG 6000 as hydrophilic carrier can be successfully used
      for improvement of dissolution of LM and resulted in faster onset of action as
      indicated by in vivo studies.

PMID- 25599036
TI  - What is the position of Clinical and Experimental Reproductive Medicine in its
      scholarly journal network based on journal metrics?
AB  - OBJECTIVE: Clinical and Experimental Reproductive Medicine (CERM) converted its
      language to English only beginning with the first issue of 2011. From that point
      in time, one of the goals of the journal has been to become a truly international
      journal. This paper aims to identify the position of CERM in its scholarly
      journal network based on the journal's metrics. METHODS: The journal's metrics,
      including citations, countries of author affiliation, and countries of citing
      authors, Hirsch index, and proportion of funded articles, were gathered from Web
      of Science and analyzed. RESULTS: The two-year impact factor of 2013 was
      calculated at 0.971 excluding self-citation, which corresponds to a Journal
      Citation Reports ranking of 85.9% in the category of obstetrics and gynecology.
      In 2012, 2013, and 2014, the total citations were 17, 68, and 85, respectively.
      Authors from nine countries contributed to CERM. Researchers from 25 countries
      cited CERM in their articles. The Hirsch index was six. Out of 88 original
      articles, 35 studies received funds (39.8%). CONCLUSION: Based on the journal
      metrics, changing the journal language to English was found to be successful in
      promoting CERM to international journal status.

PMID- 25599035
TI  - In vitro-in vivo evaluation of xanthan gum and eudragit inter polyelectrolyte
      complex based sustained release tablets.
AB  - INTRODUCTION: Polyelectrolyte complexes (PECs) are the association complexes
      formed between oppositely charged particles (e.g., polymer-polymer, polymer-drug
      and polymer-drug-polymer). These are formed due to electrostatic interaction
      between oppositely charged polyions. Diclofenac is a nonsteroidal anti
      inflammatory drug (NSAID) advocated in use of painful and inflammatory rheumatic
      and certain non-rheumatic conditions. The drug has a relatively short elimination
      half-life, which limits the potential for drug accumulation. As an analgesic, it
      has a fast onset and long duration of action. AIM: invitro-invivo evaluation of
      Xanthan gum and Eudragit E100 inter polyelectrolyte complex based sustained
      release tablet. MATERIALS AND METHOD: Xanthan gum and Eudragit E100 were used as
      PEC and were prepared using different proportions i.e. in 1:1 to 1:6 ratio. The
      optimum ratio of E100 and XG was 1:6 used to characterize the IPC and the
      formulation of tablet. The tablets were prepared by wet granulation using PVP K30
      as binder. RESULTS AND DISCUSSION: FT-IR and DSC studies confirmed the formation
      of IPC. Scanning Electron Microscopy (SEM) studies showed highly porous tablet
      surface. The tablets were evaluated for hardness, weight variation, and drug
      content, found to be within limits. In vitro and in vivo studies concluded that
      tablets showed sustained release profile. The short term stability study of the
      optimized formulation indicated that the formulation was stable. CONCLUSION:
      Since the Poly Electrolyte Complex delay the release of the drug, it can be
      employed in formulating sustained release matrix tablets.

PMID- 25599037
TI  - Association of the neutrophil-to-lymphocyte ratio and CA 125 with the
      endometriosis score.
AB  - OBJECTIVE: To evaluate the association between the severity of endometriosis and
      the preoperative neutrophil-to-lymphocyte ratio (NLR) and serum level of cancer
      antigen 125 (CA 125). METHODS: Data were obtained from the medical records of 419
      patients who underwent laparoscopic conservative surgery for ovarian endometrioma
      between April 2005 and March 2013. Each patient's preoperative complete blood
      count was recorded and the endometriosis score was assessed. RESULTS: The
      endometriosis score was not associated with either the NLR or the serum level of
      CA 125. The endometriosis score was negatively related to preoperative
      hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and
      mean corpuscular hemoglobin concentration. The only positive association was
      between NLR and the patients' age. NLR and preoperative serum anti-Mullerian
      hormone level were found to be negatively related. CONCLUSION: The severity of
      endometriosis was not associated with the serum level of CA 125 or the NLR. The
      presence of a negative correlation between the severity of endometriosis and red
      blood cell dynamics needs further investigation.

PMID- 25599038
TI  - Early gonadotropin-releasing hormone antagonist start improves follicular
      synchronization and pregnancy outcome as compared to the conventional antagonist
      protocol.
AB  - OBJECTIVE: To assess whether an early GnRH antagonist start leads to better
      follicular synchronization and an improved clinical pregnancy rate (CPR).
      METHODS: A retrospective cohort study. A total of 218 infertile women who
      underwent IVF between January 2011 and February 2013. The initial cohort (Cohort
      I) that underwent IVF between January 2011 and March 2012 included a total of 68
      attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH
      antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol.
      The second cohort (Cohort II) that underwent IVF between June 2012 and February
      2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were
      treated with the conventional GnRH antagonist protocol, 34 cycles with the
      modified early GnRH antagonist start protocol using highly purified human
      menopause gonadotropin and an addition of GnRH agonist to the luteal phase
      support, and 73 cycles with the GnRH agonist long protocol. RESULTS: The analysis
      of Cohort I showed that the number of mature oocytes retrieved was significantly
      higher in the early GnRH antagonist start cycles than in the conventional
      antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed
      higher but non-significant CPR/ET in the modified early GnRH antagonist start
      cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was
      comparable to that of the GnRH agonist long protocol cycles (39.7%). CONCLUSION:
      The modified early antagonist start protocol may improve the mature oocyte yield,
      possibly via enhanced follicular synchronization, while resulting in superior CPR
      as compared to the conventional antagonist protocol, which needs to be studied
      further in prospective randomized controlled trials.

PMID- 25599039
TI  - Effects of feminine cleanser Inclear on sperm motility: A prospective study.
AB  - OBJECTIVE: The objective of this study is to estimate the effects of Inclear, a
      feminine cleanser, on sperm motility. METHODS: Semen samples were obtained from
      infertile male patients. Following liquefaction, the raw semen samples were
      diluted with Ham's F-10 nutrient mixture medium containing 0.4% human serum
      albumin solution at a ratio of 1:3. The semen samples were subsequently
      centrifuged to separate the seminal plasma from the serum. The supernatant was
      discarded, and the pellet was resuspended. The sample was again centrifuged to
      remove cell debris, and the supernatant was removed. The final pellet was gently
      loosened by resuspension and incubated in medium alone as a control, and in a 10%
      solution of the medium plus Inclear. A sampling time of 30 minutes was selected
      on the basis of sperm transport studies. Sperm motility was evaluated with
      computer-assisted sperm analysis. RESULTS: A total of 20 samples were analyzed.
      The mean age of patients was 34.40+/-2.96 years. There was no difference in sperm
      concentration and motility in the two samples at 0 minute and 30 minutes of
      incubation. In both semen samples, the sperm concentration and motility decreased
      after an incubation period of 30 minutes. However, there was no statistical
      difference between the samples. Sperm concentration and motility were not
      significantly different between the control and Inclear samples after 0 minute
      and 30 minutes of incubation. CONCLUSION: Inclear has no negative effects on
      sperm motility. This product can be recommended to pregnancy planners for vaginal
      hygiene and as a vaginal lubricant.

PMID- 25599040
TI  - A healthy delivery of twins by assisted reproduction followed by preimplantation
      genetic screening in a woman with X-linked dominant incontinentia pigmenti.
AB  - The purpose of this study is to report a successful twin pregnancy and delivery
      in a female patient with X-linked dominant incontinentia pigmenti (IP) who
      underwent assisted reproductive technology followed by preimplantation genetic
      screening (PGS). A 29-year-old female with IP had a previous history of recurrent
      spontaneous abortion. A molecular analysis revealed the patient had a de novo
      mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa
      B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed,
      in which male embryos were sexed using array-based comparative genomic
      hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two
      euploid male blastocysts were transferred with a 50% probability of a viable male
      pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis
      results of each twin were normal with regard to the mutation found in the mother.
      The patient delivered healthy twin babies during the 37th week of gestation. This
      case shows the beneficial role of PGS in achieving a successful pregnancy through
      euploid male embryo gender selection in a woman with X-linked dominant IP with a
      history of multiple male miscarriages. 

PMID- 25599041
TI  - Uterine infarction in a patient with uterine adenomyosis following biochemical
      pregnancy.
AB  - Adenomyosis is a common gynecological disorder characterized by the presence of
      endometrial glands and stroma deep within the myometrium associated with
      myometrial hypertrophy and hyperplasia. Focal uterine infarction after IVF-ET in
      a patient with adenomyosis following biochemical pregnancy has not been
      previously reported, although it occurs after uterine artery embolization in
      order to control symptoms caused by fibroids or adenomyosis. We report a case of
      a nulliparous woman who had uterine adenomyosis presenting with fever, pelvic
      pain and biochemical abortion after undergoing an IVF-ET procedure and the
      detection of a slightly elevated serum hCG. Focal uterine infarction was
      suspected after a pelvic magnetic resonance imaging demonstrated preserved
      myometrium between the endometrial cavity and inner margin of the necrotic
      myometrium. This case demonstrates that focal uterine infarction should be
      considered in the differential diagnosis of acute abdominal pain, vaginal
      bleeding and infectious signs in women experiencing biochemical abortion after an
      IVF-ET procedure. 

PMID- 25599043
TI  - Initial Experience Using the 5MAXTM ACE Reperfusion Catheter in Intra-arterial
      Therapy for Acute Ischemic Stroke.
AB  - OBJECTIVES: The 5MAX ACE is a new large bore aspiration catheter available for
      vessel recanalization for treatment of acute ischemic stroke (AIS). We report our
      initial experience with its use. METHODS: A retrospective analysis of patients
      undergoing intra-arterial therapy for AIS using the 5MAX ACE reperfusion catheter
      at our institution was performed. Patient demographics, clinical characteristics
      and procedural data were obtained from chart review. Successful recanlization was
      defined as achievement of Thrombolysis in Cerebral Infarction score (TICI) 2b-3
      and time to recanalization was defined as time from groin puncture to achievement
      of at least TICI 2b recanalization. RESULTS: The 5MAX ACE was used in 15 patients
      from July-October 2013. Direct aspiration was used as the primary technique in
      10/15 (67%) patients. Out of these, aspiration alone was sufficient for
      recanalization in 3 (20%) patients. In the remaining 7 (47%) patients, additional
      devices were used. In 5/15 (33%) patients, combined aspiration/stentriever
      thrombectomy using SolitaireTM (3/5 patients) and Penumbra 3D SeparatorTM (2/5
      patients) were used as the primary technique. Successful recanlization (TICI 2b
      3) was achieved in 11/15 (73%) patients. Average time from groin puncture to
      successful recanalization was 46 +/- 30 minutes (range 14-98 minutes). There were
      no procedural complications. CONCLUSION: The 5MAX ACE is a useful recanalization
      tool, either by direct aspiration or combined stentriever/aspiration. It may be
      most advantageous with large clots in the internal carotid artery. The potential
      for effective and faster recanalization using this device alone or in combination
      may be a good topic for future study.

PMID- 25599044
TI  - Volume measurement of the intracranial aneurysm: a discussion and comparison of
      the alternatives to manual segmentation.
AB  - OBJECTIVE: Several modalities are available for volumetric measurement of the
      intracranial aneurysm. We discuss the challenges involved in manual segmentation,
      and analyze the application of alternative methods using automatic segmentation
      and geometric formulae in measurement of aneurysm volumes and coil packing
      density. METHODS: The volumes and morphology of 38 aneurysms treated with
      endovascular coiling at a single center were measured using three-dimensional
      rotational angiography (3DRA) reconstruction software using automatic
      segmentation. Aneurysm volumes were also calculated from their height, width,
      depth, size of neck, and assumed shape in 3DRA images using simple geometric
      formulae. The aneurysm volumes were dichotomized as "small" or "large" using the
      median volume of the studied population (54 mm(3)) measured by automatic
      segmentation as the cut-off value for further statistical analysis. RESULTS: A
      greater proportion of aneurysms were categorized as being "small" when geometric
      formulae were applied. The median aneurysm volumes obtained were 54.5 mm(3) by
      3DRA software, and 30.6 mm(3) using mathematical equations. An underestimation of
      aneurysm volume with a resultant overestimation in the calculated coil packing
      density (p = 0.002) was observed. CONCLUSION: Caution must be exercised in the
      application of simple geometric formulae in the management of intracranial
      aneurysms as volumes may potentially be underestimated and packing densities
      falsely elevated. Future research should focus on validation of automatic
      segmentation in volumetric measurement and improving its accuracy to enhance its
      application in clinical practice.

PMID- 25599045
TI  - Middle meningeal artery arising from the basilar artery.
AB  - Various anomalies for the origin of the middle meningeal artery (MMA) have been
      described in the literature. However, origin of the MMA from the basilar trunk is
      an extremely rare variant. We report on a 54-year-old female who presented with
      frequent headaches; magnetic resonance imaging showed a right parietal
      meningioma. The abnormal origin of the middle meningeal artery from the basilar
      artery was diagnosed by angiography performed for preoperative embolization of
      the tumor. We report on the case with a review of the embryologic basis, possible
      explanations for this aberrant origin, and its clinical implications. 

PMID- 25599042
TI  - A comparative review of the hemodynamics and pathogenesis of cerebral and
      abdominal aortic aneurysms: lessons to learn from each other.
AB  - OBJECTIVE: Cerebral aneurysms (CAs) and abdominal aortic aneurysms (AAAs) are
      degenerative vascular pathologies that manifest as abnormal dilations of the
      arterial wall. They arise with different morphologies in different types of blood
      vessels under different hemodynamic conditions. Although treated as different
      pathologies, we examine common pathways in their hemodynamic pathogenesis in
      order to elucidate mechanisms of formation. MATERIALS AND METHODS: A systematic
      review of the literature was performed. Current concepts on pathogenesis and
      hemodynamics were collected and compared. RESULTS: CAs arise as saccular
      dilations on the cerebral arteries of the circle of Willis under high blood flow,
      high wall shear stress (WSS), and high wall shear stress gradient (WSSG)
      conditions. AAAs arise as fusiform dilations on the infrarenal aorta under low
      blood flow, low, oscillating WSS, and high WSSG conditions. While at opposite
      ends of the WSS spectrum, they share high WSSG, a critical factor in arterial
      remodeling. This alone may not be enough to initiate aneurysm formation, but may
      ignite a cascade of downstream events that leads to aneurysm development. Despite
      differences in morphology and the structure, CAs and AAAs share many
      histopathological and biomechanical characteristics. Endothelial cell damage,
      loss of elastin, and smooth muscle cell loss are universal findings in CAs and
      AAAs. Increased matrix metalloproteinases and other proteinases, reactive oxygen
      species, and inflammation also contribute to the pathogenesis of both aneurysms.
      CONCLUSION: Our review revealed similar pathways in seemingly different
      pathologies. We also highlight the need for cross-disciplinary studies to aid in
      finding similarities between pathologies.

PMID- 25599046
TI  - An unruptured anterior communicating artery aneurysm with bilateral infraoptic
      anterior cerebral arteries. Case report and review of the literature.
AB  - Variations of the anterior cerebral artery-anterior communicating artery complex
      are commonly identified in aneurysm surgery. An infraoptic course of the anterior
      cerebral artery is exceedingly rare. Robison first described this anomaly from an
      anatomic dissection in 1959. A unilateral anomalous infraoptic anterior cerebral
      artery is more common than anomalies of bilateral infraoptic anterior cerebral
      arteries. We present the case of an unruptured aneurysm at the anterior
      communicating artery in a patient with bilateral infraoptic anterior cerebral
      arteries, identified by computed tomography angiography and verified during
      surgery. Implications for aneurysm formation and surgical treatment are
      discussed. 

PMID- 25599048
TI  - Processing of the explanted heart.
AB  - Analysis of the explanted hearts from heart transplant recipients provides
      valuable clinical samples, which can be used to study the anatomy and pathology
      of the heart. PubMed database was employed as the article source of this review.
      This article summarized the processing methods of the explanted heart, including
      dissection, histopathologic examination, cryopreservation, and genetic testing. A
      standard processing of explanted hearts ensures the quality and reliability of
      samples. Analysis of explanted hearts facilitates the diagnostic assessment and
      therapy strategy of heart diseases. 

PMID- 25599047
TI  - Presurgical pulmonary evaluation in renal transplant patients.
AB  - Patients with chronic renal failure (CRF) due to various mechanisms are prone to
      significant pulmonary comorbidities. With the improvements in renal replacement
      therapy (RRT), patients with CRF are now expected to live longer, and thus may
      develop complications in the lung from these processes. The preferred treatment
      of CRF is kidney transplantation and patients who are selected to undergo
      transplant must have a thorough preoperative pulmonary evaluation to assess
      pulmonary status and to determine risk of postoperative pulmonary complications.
      A MEDLINE((r))/PubMed((r)) search was performed to identify all articles
      outlining the course of pre-surgical pulmonary evaluation with an emphasis on
      patients with CRF who have been selected for renal transplant. Literature review
      concluded that in addition to generic pre-surgical evaluation, renal transplant
      patients must also undergo a full cardiopulmonary and sleep evaluation to
      investigate possible existing pulmonary pathologies. Presence of any risk factor
      should then be aggressively managed or treated prior to surgery. 

PMID- 25599049
TI  - Oral hydration for prevention of contrast-induced acute kidney injury in elective
      radiological procedures: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: The reports on efficacy of oral hydration treatment for the
      prevention of contrast-induced acute kidney injury (CIAKI) in elective
      radiological procedures and cardiac catheterization remain controversial. AIMS:
      The objective of this meta-analysis was to assess the use of oral hydration
      regimen for prevention of CIAKI. MATERIALS AND METHODS: Comprehensive literature
      searches for randomized controlled trials (RCTs) of outpatient oral hydration
      treatment was performed using MEDLINE, EMBASE, Cochrane Database of Systematic
      Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews, and
      clinicaltrials.gov from inception until July 4(th), 2014. Primary outcome was the
      incidence of CIAKI. RESULTS: Six prospective RCTs were included in our analysis.
      Of 513patients undergoing elective procedures with contrast exposures,45 patients
      (8.8%) had CIAKI. Of 241 patients with oral hydration regimen, 23 (9.5%)
      developed CIAKI. Of 272 patients with intravenous (IV) fluid regimen, 22 (8.1%)
      had CIAKI. Study populations in all included studies had relatively normal kidney
      function to chronic kidney disease (CKD) stage 3. There was no significant
      increased risk of CIAKI in oral fluid regimen group compared toIV fluid regimen
      group (RR = 0.94, 95% confidence interval, CI = 0.38-2.31). CONCLUSIONS:
      According to our analysis,there is no evidence that oral fluid regimen is
      associated with more risk of CIAKI in patients undergoing elective procedures
      with contrast exposures compared to IV fluid regimen. This finding suggests that
      the oral fluid regimen might be considered as a possible outpatient treatment
      option for CIAKI prevention in patients with normal to moderately reduced kidney
      function.

PMID- 25599052
TI  - Biochemical and Pathological Study of Hydroalcoholic Extract of Achillea
      millefolium L. on Ethylene Glycol-Induced Nephrolithiasis in Laboratory Rats.
AB  - BACKGROUND: Nephrolithiasis is of the most prevalent urinary tract disease. It
      seems worthwhile to replace the conventional treatments with more beneficial and
      safer agents, particularly herbal medicines which are receiving an increasing
      interest nowadays. AIMS: In this study, we investigated the protective and
      curative effects of Achillea millefolium L. on ethylene glycol (EG)-induced
      nephrolithiasis in rats. MATERIALS AND METHODS: The extract of A. millefolium was
      prepared by soxhlet method. Forty male Wistar rats were randomly divided into
      five groups (N = 8) as follows. The negative control (group A) received tap
      drinking water. Rats in sham (positive control group B), curative (group C and
      D), and preventive (group E) groups all received 1% EG in drinking water
      according to the experimental protocol for 30 days. In the curative groups,
      dosages of 200 and 400 mg/kg body weight (BW) of A. millefolium extract were
      administered orally from day 15 to the end of the experiment, group C and D,
      respectively. Group E received 200 mg/kg A. millefolium extract from the 1(st)
      day throughout the experiment. Urinary oxalate and citrate concentrations were
      measured by spectrophotometer on the first and 30(th) days. On day 31, the
      kidneys were removed and examined histopathologically for counting the calcium
      oxalate (CaOx) deposits in 50 microscopic fields. RESULTS: In the curative and
      preventive groups, administration of A. millefolium extract showed significant
      reduction in urinary oxalate concentration (P < 0.05). Also, urinary citrate
      concentration was significantly increased in group C, D, and E. The CaOx deposits
      significantly decreased in group C to E compared with the group B. CONCLUSIONS:
      According to our results, A. millefolium extract had preventive and curative
      effects on EG-induced renal calculi.

PMID- 25599050
TI  - Dual blockade of Renin Angiotensin system in reducing the early changes of
      diabetic retinopathy and nephropathy in a diabetic rat model.
AB  - BACKGROUND: Diabetes mellitus is a real pandemic of the modern world and the
      incidence of the disease is increasing at a tremendous rate with a number of
      complications involving major systems of the human body. The renin angiotensin
      system (RAS) is considered to be involved in most of the pathological processes
      that result in diabetic nephropathy and retinopathy. AIM: The study was designed
      to evaluate and compare effects of ramipril (angiotensin-converting enzyme
      inhibitor-ACEI) and telmisartan (angiotensin II receptor blocker - ARBs)
      combinations on the progression of retinopathy and nephropathy in the
      streptozotocin (STZ) induced diabetic model. MATERIALS AND METHODS: Diabetic
      state in rats was induced by chemical method using STZ 55 mg/kg
      intraperitoneally. Diabetic renal tubulopathy and interstitial inflammatory
      changes were done. Diabetic retinopathy manifested in the form of vacuolar
      changes in the inner plexiform and the ganglionic layers of the retina was
      observed. RESULTS: Treatments with ACEI and ARBs reduced the incidence of the
      occurrence of cataract. The effect of combinational drugs of ACEI (ramipril) and
      AT1 receptor blocker (Telmisartan) was evaluated. The drugs used in combinations
      showed improvement in the histopathological and biochemical changes of the
      diabetic animals, both for the retina and kidney. CONCLUSION: The efficacy of the
      drugs suggests a pivotal role of the local RAS system in the pathogenesis of
      tubulopathy in the kidney and neuronal damage in the retina of the diabetic
      animals.

PMID- 25599051
TI  - Saliva alpha-Synuclein and A High Extinction Coefficient Protein: A Novel
      Approach in Assessment Biomarkers of Parkinson's Disease.
AB  - BACKGROUND: The pathological hallmark of Parkinson's disease (PD) is the
      appearance of intracytoplasmic inclusions known as Lewy bodies in which its
      principal component is alpha-synuclein. AIM: This study aimed to determine
      salivary alpha-synuclein and the extinction coefficient of the saliva protein as
      biomarkers of PD. MATERIALS AND METHODS: This observational study was done in
      Department of Pharmacology, College of Medicine in cooperation with Department of
      Oral Medicine, College of Dentistry at Al-Mustansiriya University in Baghdad,
      Iraq from September 2013 to March 2014. A total number of 20 PD patients and 20
      healthy subjects were enrolled in the study. Unstimulated saliva obtained from
      each participant obtained for determination of salivary flow rate, saliva protein
      and alpha-synuclein using enzyme linked immune sorbent assay (ELISA) technique.
      RESULTS: Total saliva protein and uncontaminated protein with nucleic acids are
      significantly higher in PD compared with healthy subjects. The mean extinction
      coefficient of that protein is 27.25 M.cm(-1) which significantly (P < 0.001)
      less than corresponding value of healthy subjects (33.48 M.cm(-1) ). Saliva alpha
      synuclein level is significantly less in PD (65 +/- 52.2 pg/ml) than healthy
      subjects (314.01 +/- 435.9 pg/ml). CONCLUSIONS: We conclude that saliva alpha
      synuclein serves as a biomarker for PD if its level compared with healthy
      subjects, and a specific protein with extinction coefficient 27.25 M.cm-1 is
      detected in saliva of Parkinson's patients.

PMID- 25599055
TI  - Kaposi Sarcoma as Initial Presentation of HIV Infection.
AB  - CONTEXT: Kaposi's sarcoma (KS), a vascular tumor that manifests as nodular
      lesions on the skin and to a lesser extent, the visceral organs, is the most
      common neoplasm encountered in human immunodeficiency virus (HIV)-infected
      patients. It consists of an angiosarcomatous change of not only the epithelial
      and mucous membrane-associated connective tissue in various sites, for example,
      skin, gastrointestinal system, lungs, and so on, but may also involve non
      epithelial organs, such as lymph nodes. Surgical excision is the line of
      management for the tumor. CASE REPORT: We present one case of a 65-year-old
      heterosexual Indian male, clinically unsuspected for acquired immunodeficiency
      syndrome (AIDS) who presented with multiple non-blanching, bluish-red nodules on
      all extremities, chest, back and bilateral submandibular and cervical
      lymphadenopathy. Fine needle aspiration cytology (FNAC) was performed from
      subcutaneous nodule and lymph node. Smears showed hypercellular plump spindle
      cell groups in a hemorrhagic background. Diagnosis was given as low-grade spindle
      cell neoplasm consistent with KS, which was later confirmed on histopathology.
      CONCLUSION: The first line diagnostic aid of FNAC has several advantages over the
      traditional biopsy in testing such vascular tumors. The latter is generally
      needed for confirmation of KS. However, FNAC of such vascular tumors has
      advantages of better patient compliance, ease of procedure, no recurrences, and
      safety in immuno-compromised patients. Ancillary studies can be done on aspirates
      along with polymerase chain reaction (PCR) amplification techniques in confirming
      the detection of associated human herpes virus-8 (HHV-8) infection with KS.

PMID- 25599054
TI  - Crohnic kidney disease: recurrent acute kidney failure in a patient with Crohn's
      disease.
AB  - CONTEXT: Short bowel syndrome is a rare and devastating complication in chronic
      inflammatory bowel disease following functional or anatomic loss of extensive
      segments of the intestine. CASE REPORT: A 60-year-old male patient with Crohn's
      disease had undergone multiple resections of the intestine and developed short
      bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and
      magnesium intake, he suffered from recurrent acute kidney injury due to profound
      volume depletion and those electrolyte deficiencies. Administration of
      intravenous fluid and electrolyte repleacement treatment at regular intervals
      prevented further kidney injuries. CONCLUSION: We present a case of recurrent
      acute kidney failure in a patient with Crohn's disease, and aimed to remark
      importance of receiving sufficient parenteral fluid and electrolyte support in
      those with short bowel syndrome.

PMID- 25599053
TI  - Spasmolytic and Anti-Spasmodic Action of Trachyspermum ammi Essence on Rat's
      Ileum Contraction.
AB  - BACKGROUND: Trachyspermum ammi is a plant of umbelliferae family and has been
      traditionally used in the treatment of many gastrointestinal disorders such as
      indigestion, colic, and diarrhea. Our previous study demonstrated that aqueous
      extract of Trachyspermum ammi reduced the contractile activity of rat's ileum.
      AIMS: This study was designed to examine the effect of Trachyspermum ammi essence
      on acetylcholine-induced contraction in isolated rat's ileum. MATERIALS AND
      METHODS: In this experimental procedure, the tissue samples were suspended from
      the transducer lever and mounted on the organ bath containing Tyrode's solution.
      Isotonic responses were recorded by using an isotonic transducer and the
      amplitude of contractions. This process was induced by cumulative logarithmic
      concentrations of acetylcholine before and after exposing tissue by saline and
      different concentrations of essence. RESULTS: The chemical constituents of the
      essence from distillate extract of Trachyspermum ammi seeds were studied by gas
      chromatography mass spectrometry (GC-MS) and the chemical analysis showed many
      components in which thymol was the main constituent. Our findings showed that the
      essence derived from the extract in all concentrations used in this study (0.002,
      0.005, and 0.01% V/V) significantly reduced acetylcholine-induced contractions
      (47.34, 60.46, and 86%, respectively, P < 0.05). The same concentrations of the
      essence also exhibit a significant anti-spasmodic action on acetylcholine-induced
      contractions (0.1,88.3, and 90.7%, respectively, P < 0.05). CONCLUSION: Since
      thymol was the major constituent of our samples of Trachyspermum ammi, the
      relaxant effect observed in this study is probably due to this agent which can
      exert an anti-cholinergic property.

PMID- 25599057
TI  - Editorial.

PMID- 25599056
TI  - Rotator cuff metastases: a report of two cases with literature review.
AB  - CONTEXT: Distant metastases of primary malignancies to the skeletal muscle tissue
      are a very rare event. Distant metastases that affect the rotator cuff are even
      rarer, and only a few of cases have been reported so far. CASE REPORT: The
      present article reports two cases that presented to our hospital with the
      complaint of shoulder pain and had a soft tissue mass affecting the muscles of
      the rotator cuff and invading the neighboring bone compartments. One of the
      patients developed mucoepidermoid cancer metastasis of the submandibular gland,
      and the other was found to have a malignant epithelial tumor metastasized from
      the lower lobe of the right lung, whose primary origin could not be diagnosed
      until the imaging examinations were employed. Ultrasound and magnetic resonance
      imaging findings are presented in this paper. CONCLUSION: Metastases to the
      muscle tissues could be misdiagnosed as primary sarcomas. Because the therapy
      regiments and prognoses are fairly different for these two entities, the
      possibility of a metastasis to the muscle tissue must be considered as a
      differential diagnosis for case of painful soft tissue mass. Ultrasound is very
      useful in detection of the lesion and acts as a very important tool during
      guidance for biopsy. Magnetic resonance imaging, however, is a very valuable
      asset in the evaluation of the borders of the soft tissue mass and its invasive
      effect on the bony tissues. Particularly when the features such as lobulated
      contours, peripheral edema, and intratumoral necrosis exist, the possibility of
      metastases must be considered.

PMID- 25599058
TI  - Investigation of the entrance surface dose and dose to different organs in lumbar
      spine imaging.
AB  - BACKGROUND: Dose assessment using proper dosimeters is especially important in
      radiation protection optimization and imaging justification in diagnostic
      radiology. OBJECTIVE: The aim of this study is to obtain the Entrance Skin Dose
      (ESD) of patients undergoing lumbar spine imaging using two thermoluminescence
      dosimeters TLD-100 (LiF: Mg, Ti) and GR-200 (LiF: Mg, Cu, P) and also to obtain
      the absorbed dose to different organs in lumbar spine imaging with several views.
      METHODS: To measure the ESD values of the patients undergoing lumbar spine
      imaging, the two TLD types were put on their skin surface. The ESD values for
      different views of lumbar spine imaging were also measured by putting the TLDs at
      the surface of the Rando phantom. Several TLD chips were inserted inside
      different organs of Rando phantom to measure the absorbed dose to different
      organs in lumbar spine imaging. RESULTS: The results indicate that there is a
      close agreement between the results of the two dosimeters. Based on the results
      of this experiment, the ESD dose of the 16 patients included in this study varied
      between 2.71 mGy and 26.29 mGy with the average of 11.89 mGy for TLD-100, and
      between 2.55 mGy and 27.41 mGy with the average of 12.32 mGy for GR-200
      measurements. The ESDs obtained by putting the two types of TLDs at the surface
      of Rando phantom are in close agreement. CONCLUSION: According to the results,
      the GR200 has greater sensitivity than the TLD-100.

PMID- 25599059
TI  - A Monte Carlo Study for Photoneutron Dose Estimations around the High-Energy
      Linacs.
AB  - BACKGROUND: High-energy linear accelerator (linac) is a valuable tool and the
      most commonly used device for external beam radiation treatments in cancer
      patients. In the linac head, high-energy photons with energies above the
      threshold of (gamma,n) interaction produce photoneutrons. These photoneutrons
      deliver the extra dose to the patients undergoing radiation treatment and
      increase the risk of secondary cancer. OBJECTIVE: In this study, a simplified
      model of the linac head was simulated and photoneutron dose equivalent was
      calculated at the isocenter and maze in the sphere detector. In addition, the
      absorbed and equivalent dose of photoneutron were estimated in the some organs of
      the phantom. METHODS: The simulations were made using the Monte Carlo code. The
      ICRP reference adult male voxel phantom was used as the human body model for
      dosimetry calculations. RESULTS: The results of dose calculations at the
      isocenter and maze showed that photoneutron dose decreases as the function of
      distance from the isocenter and increases with increasing the distance from the
      entrance maze. CONCLUSION: It is concluded that the simplified model of linac
      head is a useful and reliable method in dosimetry calculations. Calculations
      illustrated that the photoneutron dose is not negligible and duo to its harmful
      biological effects on body, it should be considered in the treatment plans.

PMID- 25599060
TI  - Effects of defining realistic compositions of the ocular melanoma on proton
      therapy.
AB  - BACKGROUND: Recent studies in eye plaque brachytherapy have shown a considerable
      difference between the dosimetric results using water phantom and a model of
      human eye containing realistic materials. In spite of this fact, there is a lack
      of simulation studies based on such a model in proton therapy literatures. In the
      presented work, the effect of utilizing an eye model with ocular media on proton
      therapy is investigated using the MCNPX Monte Carlo Code. METHODS: Two different
      eye models are proposed to study the effect of defining realistic materials on
      dose deposition due to utilizing pencil beam scanning (PBS) method for proton
      therapy of ocular melanoma. The first model is filled with water, and the second
      one contains the realistic materials of tumor and vitreous. Spread out Bragg
      peaks (SOBP) are created to cover a typical tumor volume. Moreover, isodose
      curves are figured in order to evaluate planar variations of absorbed dose in two
      models. RESULTS: The results show that the maximum delivered dose in ocular media
      is approximately 12-32% more than in water phantom. Also it is found that using
      the optimized weighted beams in water phantom leads to disturbance of uniformity
      of SOBP in ocular media. CONCLUSION: Similar to the results reported in eye
      brachytherapy published papers, considering the ocular media in simulation
      studies leads to a more realistic assessment of sufficiency of the designed
      proton beam in tissue. This effect is of special importance in creating SOBP, as
      well as in delivered dose in the tumor boundaries in proton pencil beam scanning
      method.

PMID- 25599061
TI  - Evaluation of the effects of injection velocity and different gel concentrations
      on nanoparticles in hyperthermia therapy.
AB  - BACKGROUND AND OBJECTIVE: In magnetic fluid hyperthermia therapy, controlling
      temperature elevation and optimizing heat generation is an immense challenge in
      practice. The resultant heating configuration by magnetic fluid in the tumor is
      closely related to the dispersion of particles, frequency and intensity of
      magnetic field, and biological tissue properties. METHODS: In this study, to
      solve heat transfer equation, we used COMSOL Multiphysics and to verify the
      model, an experimental setup has been used.  To show the accuracy of the model,
      simulations have been compared with experimental results. In the second part, by
      using experimental results of nanoparticles distribution inside Agarose gel
      according to various gel concentration, 0.5%, 1%, 2%, and 4%, as well as the
      injection velocity, 4 uL/min, 10 uL/min, 20 uL/min, and 40 uL/min, for 0.3 cc
      magnetite fluid, power dissipation inside gel has been calculated and used for
      temperature prediction inside of the gel. RESULTS: The Outcomes demonstrated that
      by increasing the flow rate injection at determined concentrations, mean
      temperature drops. In addition, 2% concentration has a higher mean temperature
      than semi spherical nanoparticles distribution. CONCLUSION: The results may have
      implications for treatment of the tumor and any kind of cancer diseases.

PMID- 25599062
TI  - The mechanisms of radiation-induced bystander effect.
AB  - The radiation-induced bystander effect is the phenomenon which non-irradiated
      cells exhibit effects along with their different levels as a result of signals
      received from nearby irradiated cells. Responses of non-irradiated cells may
      include changes in process of translation, gene expression, cell proliferation,
      apoptosis and cells death. These changes are confirmed by results of some In-Vivo
      studies. Most well-known important factors affecting radiation-induced bystander
      effect include free radicals, immune system factors, expression changes of some
      genes involved in inflammation pathway and epigenetic factors. 

PMID- 25599063
TI  - Impact of Psychological Problems and Marital Adjustment of Iranian Veterans on
      Their Children's Quality of Life and Happiness.
AB  - BACKGROUND: The Iran-Iraq war during the 1980-1988 has left many consequences on
      veterans and their families that persist long after the war ended. OBJECTIVES:
      The aim of this study was to evaluate the impact of psychological problems and
      marital adjustment of Iranian veterans on their children's quality of life and
      happiness 24 years after the war ended. PATIENTS AND METHODS: The sample was all
      children of veterans in Isfahan city that registered by Veterans and Martyrs
      Affair Foundation (VMAF). One hundred sixty-three veterans were selected by
      systematic randomized sampling and the symptom checklist-90-revised (SCL-90-R)
      and dyadic adjustment scale (DAS) were administered for them. Their wives filled
      out the DAS and their children answered to World Health Organization Quality of
      Life-Brief version (WHOQOL-BREF) and Oxford Happiness Inventory (OHI). The data
      from questionnaires completed by 149 families were analyzed using the multiple
      regressions analysis. RESULTS: Global Severity Index (GSI) scores of veterans and
      veteran's age were inversely correlated with the scores of children's quality of
      life, while marital adjustment of parents and number of rooms in house were
      positively correlated. Mother's age was inversely correlated with the scores of
      children's happiness, while marital adjustment of the parents, the number of
      rooms in their house and the number of children were positively correlated.
      CONCLUSIONS: In veterans' family, psychological health of the veterans and
      marital adjustment of the parents have a significant relationship with their
      children's quality of life and happiness.

PMID- 25599064
TI  - Plate on plate technique of minimally invasive percutaneous plate osteosynthesis
      in distal tibial fractures, an easy and inexpensive method of fracture fixation.
AB  - BACKGROUND: Plate on plate technique can lessen operative time and patient
      morbidity. OBJECTIVES: This study aimed to evaluate the outcomes of minimally
      invasive percutaneous plate osteosynthesis (MIPPO) using plate on plate technique
      of locking plate fixation for closed fractures of distal tibia in a prospective
      study. PATIENTS AND METHODS: Twenty-five patients with distal tibial fractures
      were treated by MIPPO using locking plate by plate on plate technique.
      Preoperative variables including age of patient, mode of trauma, type of fracture
      and soft tissue status were recorded for each patient. Perioperative variables
      included surgical time and radiation exposure. Postoperative variables included
      wound status, time to union, return to activity and the American orthopaedic foot
      and ankle score (AOFAS). RESULTS: All the fractures had united at one year. The
      average time to union was 16.8 weeks. There were two cases of superficial
      infection and two cases of deep infection, which required removal of hardware
      after the fracture was united. The average AO foot and ankle score was 83.6 in
      our study population. CONCLUSIONS: MIPPO using locking plate by plate on plate
      technique was a safe, effective, inexpensive and easily reproducible method for
      the treatment of distal tibial fractures in properly selected patients, which
      minimized operative time and soft tissue morbidity.

PMID- 25599065
TI  - Spinal cord injury without radiological abnormality in adult thoracic spinal
      trauma.
AB  - INTRODUCTION: Spinal cord injury without radiological abnormality (SCIWORA) is a
      rare entity and usually involves the cervical spine. Thoracic spine involvement
      is very rare due to the stability provided by the rib cage. The mechanisms of
      injury and pathophysiology are still debatable. CASE PRESENTATION: We present a
      case of an adult male who had road traffic accident and presented with
      paraplegia. The initial radiological investigations carried out in the emergency
      department were reported to be normal, however, subsequent magnetic resonance
      imaging revealed spinal cord contusion without vertebral column disruption. The
      patient recovered partially with conservative treatment measures including bed
      rest and methylprednisolone. CONCLUSIONS: Spinal trauma patients presenting with
      neurological deficit but no radiological abnormality should be treated as a case
      of SCIWORA.

PMID- 25599066
TI  - Evaluation of the use and reasons for not using a helmet by motorcyclists
      admitted to the emergency ward of shahid bahonar hospital in kerman.
AB  - BACKGROUND: Motorcycle crashes are the cause of severe morbidity and mortality
      especially because of head injuries. It seems that wearing a helmet has an
      effective role in protection against head injuries. Nevertheless, motorcyclists
      usually have no tendency to wear a helmet when driving in cities and have several
      reasons for this behavior. OBJECTIVES: This study aimed to evaluate the use and
      reasons for not using a helmet by motorcyclists admitted to an emergency ward of
      a trauma hospital due to accident in Kerman, Iran. PATIENTS AND METHODS: This
      study was carried out by recoding the opinions of motorcyclists who had been
      transferred to the emergency ward of Shahid Bahonar Hospital (Kerman/Iran). Since
      no data was available on the frequency of the use of helmets, a pilot study was
      carried out and a sample size of 377 was determined for the main study. Then a
      researcher-made questionnaire was used to investigate the motorcyclists' reasons
      for not using a helmet. RESULTS: Only 21.5% of the motorcyclists had been wearing
      helmets at the time of the accident. The most frequent reasons for not using a
      helmet were the heavy weight of the helmet (77%), feeling of heat (71.4%), pain
      in the neck (69.4%), feeling of suffocation (67.7%), limitation of head and neck
      movements (59.6%) and all together, physical discomfort was the main cause of not
      wearing a helmet during motorcycle rides. CONCLUSIONS: In general, it appears
      that it is possible to increase the use of helmets by eliminating its physical
      problems, and increasing the knowledge of community members in relation to the
      advantages of helmet use, which will result in a significant decrease in traumas
      resulting from motorcycle accidents.

PMID- 25599067
TI  - Dependency in activities of daily living following limb trauma in elderly
      referred to shahid beheshti hospital, kashan-iran in 2013.
AB  - BACKGROUND: Activities of daily living (ADL) are an important indicator of health
      and independence in elderly. It provides useful information for proper planning
      in the field of elderly care. Trauma in elderly population is frequent and can
      negatively affect the independence in ADL. OBJECTIVES: The purpose of the present
      study was to evaluate elderly independence in activities of daily living (ADL)
      following limb trauma and its related factors in patients referred to trauma
      emergency ward of Shahid Beheshti Hospital, Kashan, Iran, in 2013. PATIENTS AND
      METHODS: This descriptive study was conducted on 200 traumatic patients admitted
      to trauma emergency ward of Shahid Beheshti Hospital in 2013. The questionnaire
      used in this study had three parts as demographic data, information related to
      trauma and ISADL (independency scale of activities of daily living). ISADL was
      completed in emergency ward to declare pretraumatic status; it was also completed
      1 and 3 months after trauma. Statistical analysis was conducted by Chi-square
      test, One-way and two-factor ANOVA, and Multiple regression analysis. Data
      analysis was conducted using SPSS software, version 16. RESULTS: The average age
      of participants was 70.57 +/- 9.05 years. In total, 80.5% of the elderly were
      completely independent in ISADL before trauma; this decreased to 13.5% one month
      after trauma. Besides, 32% of the elderly were completely or relatively dependent
      three months after trauma. Two-factor ANOVA showed a significant association
      between the scores of ISADL, the time interval and the type and location of an
      injured organ, and having the surgery as a treatment. CONCLUSIONS: More than
      three-quarters of the elderly were independent in ISADL before the trauma, but
      trauma in elderly patients had a substantial negative effect on patients' ability
      and ADL function.

PMID- 25599069
TI  - Clinical outcomes after posterior open elbow arthrolysis for posttraumatic elbow
      stiffness.
AB  - BACKGROUND: Loss of motion is a well-known complication after elbow trauma and in
      severe cases, arthrolysis of elbow is the procedure of choice. The posterior
      approach might have some advantages especially in post-traumatic patients who
      have undergone the same surgical approach in the past. OBJECTIVES: The aim of
      this study was to evaluate the short-term outcomes of elbow arthrolysis through
      posterior approach. Moreover, we assessed the effect of operation on the
      patients' quality of life. PATIENTS AND METHODS: During a retrospective-cohort
      study, the medical records of 14 patients (12 men, two women) whose range of
      movement had been limited post-traumatically and had undergone elbow arthrolysis
      with posterior approach were reviewed. Before intervention, the patients had a
      flexion less than 100 degrees or an extension lag of 30 degrees or more. For
      evaluation of the final outcomes, they were invited to participate in our study
      and the final range of motion, visual analogue score (VAS), disability of arm,
      shoulder and hand (DASH), Mayo elbow score (MES) and short form health survey (SF
      36) scores were measured in the patients. RESULTS: Mean age of the participants
      was 28.7 years. The interval from initial injury and arthrolysis was 16 months
      and the patients were followed for 14 months. The mean range of motion in
      patients before surgery was 35.8 degrees, which was increased to a mean of 108.9
      after the surgery, indicating a 73.1 degrees improvement. The means of VAS, DASH,
      Mayo elbow and SF-36 scores in the patients were 1.6, 34, 68 and 43,
      respectively. A significant inverse correlation was found between the
      preoperative range of motion and final range of motion. CONCLUSIONS: According to
      our results, elbow arthrolysis through posterior approach could be an effective
      technique with low complications. Since the final range of motion improved
      significantly, it might be a valuable method in promoting the patients' quality
      of life.

PMID- 25599068
TI  - Peritoneal Potassium and pH Measurement in Early Diagnosis of Acute Mesenteric
      Ischemia in Rats.
AB  - BACKGROUND: In contemporary practice, acute mesenteric ischemia (AMI) remains a
      serious cause of morbidity and mortality in abdominal emergencies. OBJECTIVES: We
      report the measurement of peritoneal fluid potassium and pH on a small series of
      rats that developed extensive AMI following the surgical ligation of superior
      mesenteric vessels and compare the results with control groups. MATERIALS AND
      METHODS: A total of 32 rats were used in our study. They were divided into four
      groups with eight rats in each one and received following treatments: group I (G
      I), 60-minute controls; group II (G-II), 120-minute controls; group III (G-III),
      60-minute cases; and group IV (G-IV), 120-minute cases. In case groups, the small
      bowel mesenteric root was double-ligated and an arrow single-lumen central venous
      catheter was passed through the skin to the peritoneum. In control groups, the
      catheter was placed without any intervention. Postoperatively, peritoneal lavage
      was performed at 60 (G-I, G-III) and 120 minutes (G-II, G-IV). RESULTS: The mean
      peritoneal potassium values were 1.3 +/- 0.3, 1.97 +/- 1.06, 2.14 +/- 0.89, and
      3.28 +/- 0.66 mmol/L in G-I, G-II, G-III, and G-IV, respectively. There were
      significant differences between G-III and G-IV (P = 0.002), between G-I and G-III
      (P = 0.024), and between G-II and G-IV (P = 0.001). The mean values of peritoneal
      fluid pH were 7.1 +/- 0.26, 6.82 +/- 0.22, 6.66 +/- 0.16, and 6.78 +/- 0.04 in G
      I, G-II, G-III, and G-IV, respectively, which indicated significant differences
      between G-I and G-III (P = 0.001) and between G-II and G-IV (P = 0.018). There
      was a significant correlation between peritoneal fluid potassium and intestine
      ischemic grade (F = 4.77, P = 0.048). CONCLUSIONS: Our findings show that for
      early detection of bowel ischemia, an evaluation of intraperitoneal potassium and
      pH was useful and with prolongation of ischemia, potassium changes were more
      significant.

PMID- 25599070
TI  - The future perspectives in transrectal prostate ultrasound guided biopsy.
AB  - Prostate cancer is one of the most common neoplasms in men. Transrectal
      ultrasound (TRUS)-guided systematic biopsy has a crucial role in the diagnosis of
      prostate cancer. However, it shows limited value with gray-scale ultrasound alone
      because only a small number of malignancies are visible on TRUS. Recently, new
      emerging technologies in TRUS-guided prostate biopsy were introduced and showed
      high potential in the diagnosis of prostate cancer. High echogenicity of
      ultrasound contrast agent reflect the increased status of angiogenesis in tumor.
      Molecular imaging for targeting specific biomarker can be also used using
      ultrasound contrast agent for detecting angiogenesis or surface biomarker of
      prostate cancer. The combination of TRUS-guided prostate biopsy and ultrasound
      contrast agents can increase the accuracy of prostate cancer diagnosis.
      Elastography is an emerging ultrasound technique that can provide the information
      regarding tissue elasticity and stiffness. Tumors are usually stiffer than the
      surrounding soft tissue. In two types of elastography techniques, shearwave
      elastography has many potential in that it can provide quantitative information
      on tissue elasticity. Multiparametric magnetic resonance imaging (MRI) from high
      resolution morphologic and functional magnetic resonance (MR) technique enables
      to detect more prostate cancers. The combination of functional techniques
      including apparent diffusion coefficient map from diffusion weighted imaging,
      dynamic contrast enhanced MR and MR spectroscopy are helpful in the localization
      of the prostate cancer. MR-ultrasound (US) fusion image can enhance the
      advantages of both two modalities. With MR-US fusion image, targeted biopsy of
      suspicious areas on MRI is possible and fusion image guided biopsy can provide
      improved detection rate. In conclusion, with recent advances in multiparametric
      MRI, and introduction of new US techniques such as contrast-enhanced US and
      elastography, TRUS-guided biopsy may evolve toward targeted biopsies rather than
      systematic biopsy for getting information reflecting the exact status of the
      prostate. 

PMID- 25599071
TI  - A multilingual evaluation of current health information on the Internet for the
      treatments of benign prostatic hyperplasia.
AB  - PURPOSE: To compare the quality of current Internet information on benign
      prostatic hyperplasia (BPH) and its surgical and medical managements across four
      Western languages and a comparative analysis of website sponsors. BPH Internet
      information quality is particularly relevant in an era of expanding, minimally
      invasive and surgical therapies. However, no comprehensive analysis exists.
      METHODS: World Health Organization Health on the Net (HON) principles may be
      applied to websites using an automated toolbar function. Using a search engine
      (www.google.com), 9,000 websites were assessed using keywords related to BPH and
      its medical and surgical treatment in English, French, German, and Spanish. The
      first 150 websites in each language had HON principles measured whilst a further
      analysis of site sponsorship was undertaken. RESULTS: Very few BPH websites had
      greater than ten per cent HON accredited with significant differences (P<0.001)
      based on terms used for BPH, its medical and surgical management. Tertiles
      (thirds) of the first 150 websites returned differences in accredited websites
      (P<0.0001). English language had most accredited websites. Odds ratios for
      different terms returning accredited websites also were significantly different
      across terms (P<0.001). Websites were largely commercially sponsored.
      CONCLUSIONS: A lack of validation of most BPH sites should be appreciated with
      discrepancies in quality and number of websites across diseases, languages and
      also between medical and alternate terms. Physicians should participate in and
      encourage the development of informative, ethical and reliable health websites on
      the Internet and direct patients to them.

PMID- 25599072
TI  - The role of 3-tesla diffusion-weighted magnetic resonance imaging in selecting
      prostate cancer patients for active surveillance.
AB  - PURPOSE: Differentiating significant cancer from insignificant cancer is a major
      challenge in active surveillance (AS) for prostate cancer. We evaluated whether
      the apparent diffusion coefficient (ADC) grade from 3-T diffusion-weighted
      magnetic resonance imaging (DW-MRI) is useful to exclude men with unfavorable
      pathological features from men meeting current AS eligibility criteria. METHODS:
      Among patients who underwent radical prostatectomy, 117 potential AS candidates
      defined according to 2013 European Association of Urology guidelines who had
      undergone preoperative 3-T DW-MRI were included. A blinded uro-radiologist graded
      the level of suspicion from the ADC map using the Likert scale from 1 to 5. The
      rate of unfavorable pathological features was evaluated according to ADC grade.
      Unfavorable pathological features were defined as non-organ-confined disease or
      pathological Gleason score>=7 (4+3). The associations between unfavorable
      pathological features and clinical variables including ADC grade (>3 vs. <=3)
      were evaluated using logistic regression analysis. RESULTS: The rates of
      unfavorable pathological features were 0.0% (0/14), 2.9% (1/34), 5.4% (2/37),
      25.0% (6/24), and 37.5% (3/8) from grades 1 to 5 (P=0.002). The predictive
      accuracy was as high as 0.804. The rates were significantly different between low
      (<=3, 3.5%) and high (>3, 28.1%, P<0.001) grades. The sensitivity, specificity,
      and positive and negative predictive values were 75.0%, 78.1%, 28.1%, and 96.5%.
      ADC grade (odds ratio [OR], 10.696; 95% confidence interval [CI], 2.675-42.773)
      was significantly associated with unfavorable pathological features, even after
      adjusting for other variables (OR, 11.274; 95% CI, 2.622-48.471). CONCLUSIONS:
      ADC grade from 3-T DW-MRI is useful to predict men with unfavorable pathologic
      features from AS candidates.

PMID- 25599073
TI  - Comparison between visual prostate symptom score and international prostate
      symptom score in males older than 40 years in rural Indonesia.
AB  - PURPOSE: To evaluate the effect of education and literacy status on completion of
      the Visual Prostate Symptom Score (VPSS) and the International Prostate Symptom
      Score (IPSS) in males aged over 40 years in a rural Indonesian area. METHODS: We
      enrolled 103 men who had visited Tc-Hillers Maumere Hospital. Four questions
      related to frequency, nocturia, weak stream, and quality of life (QoL) were
      presented by pictogram in the VPSS. Data on age, educational level, and literacy
      status were analyzed to determine associations with the capability to complete
      the IPSS and the VPSS questionnaires. Correlation test was used to identify
      correlation between the VPSS and the IPSS. RESULTS: The median age of the 103
      respondents was 60 years. A total of 69 patients (67.0%) were able to read, 99
      patients (96.1%) understood the Indonesian language, and 52 patients (50.5%) had
      an education grade>9. The IPSS was completed without assistance by 55 patients
      (53.4%) and the VPSS by 82 patients (79.6%). None of the patients who could not
      read could complete the IPSS without assistance, whereas 15 patients (44.1%) who
      could not read could complete the VPSS without assistance (P<0.001). In the
      analysis of education level, 40 of 51 patients (78.4%) with an education grade<=9
      required assistance to complete the IPSS compared with 8 of 52 patients (15.4%)
      with an education grade>9 (P>0.001). In the same groups, 19 of 51 patients
      (37.3%) compared with 2 of 52 patients (3.8%) required assistance to complete the
      VPSS (P<0.001). Total VPSS, VPSS obstructive symptoms, VPSS irritative symptoms,
      and VPSS QoL scores significantly correlated with the total IPSS, IPSS
      obstructive symptoms, IPSS irritative symptoms, and IPSS QoL, respectively
      (correlation coefficient, P-value: 0.675, <0.001; 0.503, <0.001; 0.731, <0.001;
      and 0.823, <0.001, respectively). CONCLUSIONS: The VPSS correlated significantly
      with the IPSS and could be completed without assistance by a greater proportion
      of men with low levels of education. The VPSS might be useful in evaluating men
      with lower urinary tract symptoms in rural Indonesian areas with a high level of
      illiteracy and low level of education.

PMID- 25599074
TI  - Validation of a patient reported outcome questionnaire for assessing success of
      endoscopic prostatectomy.
AB  - PURPOSE: Several international committees involved in establishing standards of
      care have recommended that patients undergoing surgery for bladder outlet
      obstruction should be assessed with patient reported outcomes (PRO). The Patient
      Global Impression of Improvement (PGI-I) is an instrument designed to measure a
      patients interpretation of symptom changes following intervention. The objective
      of this study was to validate the PGI-I as a PRO assessment following surgery for
      bladder outflow obstruction (BOO) in men with benign prostatic hyperplasia (BPH).
      METHODS: Men undergoing photoselective vaporisation of the prostate were followed
      prospectively. Pre- and postoperative International Prostate Symptom Score
      (IPSS), Quality of life (QoL) index, peak urinary flow (Qmax), and postvoid
      residual (PVR) assessments were done. The PGI-I was conducted and correlated at 3
      months postoperatively to changes in IPSS, QoL, Qmax, and PVR. RESULTS: One
      hundred and sixty-six consecutive patients were included. Following surgery, IPSS
      and QoL improved by 11 and 2.4 points (P<0.0001). PGI-I was found to correlate
      with postoperative changes in IPSS and QoL (Pearson correlation, 0.47 and 0.58,
      respectively; P<0.0001). CONCLUSIONS: This is the first study to validate the PGI
      I as a PRO measure to surgery for BOO. This suggests a potential for the PGI-I to
      be used to assess surgical therapies for BPH and may be a valuable addition for
      measuring outcomes in clinical trials evaluating surgical interventions for BPH.

PMID- 25599075
TI  - Feasibility of multiparametric prostate magnetic resonance imaging in the
      detection of cancer distribution: histopathological correlation with
      prostatectomy specimens.
AB  - PURPOSE: To prevent overtreatment, it is very important to diagnose the precise
      distribution and characteristics of all cancer lesions, including small daughter
      tumors. The purpose of this study was to evaluate the efficacy of T2-weighted
      magnetic resonance imaging (T2W), diffusion-weighted magnetic resonance imaging
      (DWI), magnetic resonance spectroscopy ((1)H-MRS), and prostate biopsy (PBx) in
      the detection of intraprostatic cancer distribution. METHODS: All patients
      underwent T2W, DWI, (1)H-MRS, and PBx followed by radical prostatectomy (RP).
      Individual prostates were divided into 12 segmental regions, each of which was
      examined for the presence or absence of malignancy on the basis of T2W, DWI, (1)H
      MRS, and PBx, respectively. These results were compared with the
      histopathological findings for RP specimens. RESULTS: We included 54 consecutive
      patients with biopsy-proven prostate cancer (mean age, 62.7 years; median
      prostate-specific antigen level, 5.7 ng/mL) in this study. We could detect cancer
      in 247 of 540 evaluable lesions. The area under the receiver operator
      characteristic curve analysis yielded a higher value for DWI (0.68) than for T2W
      (0.65), (1)H-MRS (0.54), or PBx (0.56). In 180 cancerous regions of RP specimens
      with false-negative PBx results, T2W+DWI had the highest positive rate (53.3%)
      compared with that of each sequence alone, including T2W (45.6%), DWI (41.1%),
      and (1)H-MRS (30.0%). CONCLUSIONS: Multiparametric magnetic resonance imaging
      (T2W, (1)H-MRS, DWI) enables the detection of prostate cancer distribution with
      reasonable sensitivity and specificity. T2W+DWI was particularly effective in
      detecting cancer distribution with false-negative PBx results.

PMID- 25599076
TI  - The role of transurethral resection of the prostate for patients with an elevated
      prostate-specific antigen.
AB  - PURPOSE: The aim of this study was to define the clinical significance of
      transurethral resection of the prostate (TURP) in patients with benign prostate
      hyperplasia (BPH) and an elevated prostate-specific antigen (PSA) level. METHODS:
      We retrospectively evaluated patients with BPH, lower urinary tract symptoms
      (LUTS; International Prostate Symptom Score [IPSS]>=8), an elevated serum PSA
      level (>=4 ng/mL), and previous negative transrectal ultrasonography (TRUS)
      guided prostate biopsy. The PSA level after TURP was monitored by long-term
      follow-up. The tumor detection rate on resected prostate tissue, IPSS, maximal
      urinary flow rate (Qmax), and postvoid residual urine (PVR) were analyzed.
      RESULTS: One-hundred and eighty-six patients were enrolled. Histological
      examination of resected tissue by TURP revealed prostate cancer in 12 of these
      patients (6.5%). Among 174 patients without prostate cancer, the mean PSA level
      and the PSA normalization rate in 112 patients followed up at postoperative day
      (POD) 3 months were 1.26+/-0.13 ng/mL and 94.6%, respectively. The mean PSA level
      and the PSA normalization rate were 1.28+/-1.01 ng/mL and 95.7% in 47 patients at
      1st year, 1.17+/-0.82 ng/mL and 97.1% in 34 patients at second years, and 1.34+/
      1.44 ng/mL and 97.2% in 36 patients at third years of TURP. One patient showed a
      dramatic increase in the PSA level was diagnosed with prostate cancer at 7 years
      after TURP. IPSS, quality of life, Qmax, and PVR were improved significantly at
      POD 3 months compared to baseline (P<0.05), respectively. CONCLUSIONS: TURP
      significantly reduced the serum PSA level, which was maintained for at least 3
      years. This could be helpful to screen the prostate cancer using PSA value in the
      patient with previous negative biopsy and elevated PSA. In addition, TURP
      improves IPSS, Qmax, and PVR in patients with BPH, moderate LUTS, and an elevated
      PSA level.

PMID- 25599077
TI  - Baseline participant characteristics and risk for dropout from ten obesity
      randomized controlled trials: a pooled analysis of individual level data.
AB  - INTRODUCTION: Understanding participant demographic characteristics that inform
      the optimal design of obesity RCTs have been examined in few studies. The
      objective of this study was to investigate the association of individual
      participant characteristics and dropout rates (DORs) in obesity randomized
      controlled trials (RCT) by pooling data from several publicly available datasets
      for analyses. We comprehensively characterize DORs and patterns in obesity RCTs
      at the individual study level, and describe how such rates and patterns vary as a
      function of individual-level characteristics. METHODS: We obtained and analyzed
      nine publicly-available, obesity RCT datasets that examined weight loss or weight
      gain prevention as a primary or secondary endpoint. Four risk factors for dropout
      were examined by Cox proportional hazards including sex, age, baseline BMI, and
      race/ethnicity. The individual study data were pooled in the final analyses with
      a random effect for study, and HR and 95% CIs were computed. RESULTS: Results of
      the multivariate analysis indicated that the risk of dropout was significantly
      higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46). Hispanics
      and Non-Hispanic blacks had a significantly higher dropout rate compared to non
      Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35,
      respectively). There was a significantly increased risk of dropout associated
      with advancing age (HR= 1.02, 95% CI = 1.01, 1.02) and increasing BMI (HR= 1.03,
      95% CI = 1.03, 1.04). CONCLUSION/SIGNIFICANCE: As more studies may focus on
      special populations, researchers designing obesity RCTs may wish to oversample in
      certain demographic groups if attempting to match comparison groups based on
      generalized estimates of expected dropout rates, or otherwise adjust a priori
      power estimates. Understanding true reasons for dropout may require additional
      methods of data gathering not generally employed in obesity RCTs, e.g. time on
      treatment.

PMID- 25599078
TI  - What Everybody is Doing but No One is Talking About: Use of Complementary and
      Alternative Medicine in the ANCA Associated Vasculitis Population.
AB  - : The use and impact of complementary and alternative medicine (CAM) for anti
      neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) has not been
      reported. AAV patients seeking care at our center inquired about CAM, prompting a
      formal study. Study objectives were to discern how many AAV patients used CAM and
      its perceived helpfulness in disease management. METHODS: AAV patients completed
      a CAM questionnaire between July 2011 and May 2012. Patients were 18 years or
      older and had biopsy proven and/or clinical evidence of AAV. Medical record
      abstraction supplemented data. Classification detailed CAM type including "Mind"
      or "Mind-Body". Perceived helpfulness of CAM was assessed as "very", "somewhat"
      or "not at all/don't know". RESULTS: A total of 107 patients participated and
      were a mean age of 53 (range: 18-85), 62% female; 48% proteinase 3 (PR3)-ANCA,
      44% myeloperoxidase (MPO)-ANCA and 8% ANCA-negative. Top organs involved included
      kidney (87%), joints (55%), lung (53%) and upper respiratory (53%). At least one
      type of CAM treatment or self-help practice was reported by 81% of study
      participants, with the most frequent being prayer (64%), exercise (27%) and
      massage therapy (19%). Mind-based practices were used by 28% (excluding prayer)
      and Mind-Body practices by 14%. Most practices were used to improve wellbeing,
      and Mind and Mind-Body were deemed very helpful by 83% and 87% respectively. Only
      24% of study participants discussed CAM with their physician. CONCLUSION: CAM
      practices were commonly used to improve well-being and found to be beneficial
      among AAV patients, but more open discussion is needed about CAM between
      physicians and patients.

PMID- 25599079
TI  - Neural correlates of learning in an electrocorticographic motor-imagery brain
      computer interface.
AB  - Human subjects can learn to control a one-dimensional electrocorticographic
      (ECoG) brain-computer interface (BCI) using modulation of primary motor (M1) high
      gamma activity (signal power in the 75-200 Hz range). However, the stability and
      dynamics of the signals over the course of new BCI skill acquisition have not
      been investigated. In this study, we report 3 characteristic periods in evolution
      of the high-gamma control signal during BCI training: initial, low task accuracy
      with corresponding low power modulation in the gamma spectrum, followed by a
      second period of improved task accuracy with increasing average power separation
      between activity and rest, and a final period of high task accuracy with stable
      (or decreasing) power separation and decreasing trial-to-trial variance. These
      findings may have implications in the design and implementation of BCI control
      algorithms.

PMID- 25599081
TI  - Interpreting prosodic cues in discourse context.
AB  - Two visual-world experiments investigated whether and how quickly discourse-based
      expectations about the prosodic realization of spoken words modulate
      interpretation of acoustic-prosodic cues. Experiment 1 replicated effects of
      segmental lengthening on activation of onset-embedded words (e.g. pumpkin) using
      resynthetic manipulation of duration and fundamental frequency (F0). In
      Experiment 2, the same materials were preceded by instructions establishing
      information-structural differences between competing lexical alternatives (i.e.
      repeated vs. newly-assigned thematic roles) in critical instructions. Eye
      movements generated upon hearing the critical target word revealed a significant
      interaction between information structure and target-word realization: Segmental
      lengthening and pitch excursion elicited more fixations to the onset-embedded
      competitor when the target word remained in the same thematic role, but not when
      its thematic role changed. These results suggest that information structure
      modulates the interpretation of acoustic-prosodic cues by influencing
      expectations about fine-grained acoustic-phonetic properties of the unfolding
      utterance.

PMID- 25599080
TI  - IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.
AB  - Animal cells use a wide variety of mechanisms to slow or prevent replication of
      viruses. These mechanisms are usually mediated by antiviral proteins whose
      expression and activities can be constitutive but are frequently amplified by
      interferon induction. Among these interferon-stimulated proteins, members of the
      IFITM (interferon-induced transmembrane) family are unique because they prevent
      infection before a virus can traverse the lipid bilayer of the cell. At least
      three human IFITM proteins-IFITM1, IFITM2, and IFITM3-have antiviral activities.
      These activities limit infection in cultured cells by many viruses, including
      dengue virus, Ebola virus, influenza A virus, severe acute respiratory syndrome
      coronavirus, and West Nile virus. Murine Ifitm3 controls influenza A virus
      infection in vivo, and polymorphisms in human IFITM3 correlate with the severity
      of both seasonal and highly pathogenic avian influenza virus. Here we review the
      discovery and characterization of the IFITM proteins, describe the spectrum of
      their antiviral activities, and discuss potential mechanisms underlying these
      effects.

PMID- 25599082
TI  - Social Networks Influence Hispanic College Women's HPV Vaccine Uptake Decision
      making Processes.
AB  - This qualitative study was designed to assess current and preferred social
      networks that influence human papillomavirus (HPV) vaccine decision making in a
      sample of Hispanic college women. Individual, semi-structured interviews were
      conducted with 41 Hispanic college women attending a large southeastern Hispanic
      serving institution. Television commercials and discussions with mothers were
      found to be the most influential social networks for current HPV vaccination
      beliefs. Internet sites, close family members, and healthcare providers'
      communications were preferred social networks for HPV vaccine information.
      Perceived accessibility and sense of comfort influenced the order in which these
      social networks' communications would be accepted. Findings suggest that Hispanic
      college women utilize specific social networks to gather information and make
      decisions about HPV vaccination. Continued efforts are needed to promote further
      understanding of the purpose of the HPV vaccine via these preferred sources of
      information.

PMID- 25599083
TI  - On Training Targets for Supervised Speech Separation.
AB  - Formulation of speech separation as a supervised learning problem has shown
      considerable promise. In its simplest form, a supervised learning algorithm,
      typically a deep neural network, is trained to learn a mapping from noisy
      features to a time-frequency representation of the target of interest.
      Traditionally, the ideal binary mask (IBM) is used as the target because of its
      simplicity and large speech intelligibility gains. The supervised learning
      framework, however, is not restricted to the use of binary targets. In this
      study, we evaluate and compare separation results by using different training
      targets, including the IBM, the target binary mask, the ideal ratio mask (IRM),
      the short-time Fourier transform spectral magnitude and its corresponding mask
      (FFT-MASK), and the Gammatone frequency power spectrum. Our results in various
      test conditions reveal that the two ratio mask targets, the IRM and the FFT-MASK,
      outperform the other targets in terms of objective intelligibility and quality
      metrics. In addition, we find that masking based targets, in general, are
      significantly better than spectral envelope based targets. We also present
      comparisons with recent methods in non-negative matrix factorization and speech
      enhancement, which show clear performance advantages of supervised speech
      separation.

PMID- 25599084
TI  - Issues pertaining to PET imaging of liver cancer.
AB  - Positron emission tomography (PET) imaging using 2-deoxy-2-[F-18]fluoro-D-glucose
      (FDG) has proven valuable in the diagnosis, staging and restaging for many
      cancers. However, its application for liver cancer has remained limited owing in
      part to the relatively high background uptake of the tracer in the liver plus the
      significant variability of the tumor specific uptake in liver cancer among
      patients. Thus, for primarily liver cancer, in particular, hepatocellular
      carcinoma (HCC), radio-tracers with better tumor-enhancing uptake/retention are
      still sought in order to harness the great power of PET imaging. Here, we
      reviewed some recent investigations with lipid-based small molecule PET radio
      tracers with relevance to fasting, and discuss their potential in the diagnosis
      and staging of HCCs.

PMID- 25599086
TI  - A rationally designed nanoparticle for RNA interference therapy in B-lineage
      lymphoid malignancies.
AB  - The purpose of the present study was to further evaluate the biologic
      significance of the CD22DeltaE12 molecular lesion and determine if it could serve
      as a molecular target for RNA interference (RNAi) therapy. We show that both
      pediatric and adult B-lineage lymphoid malignancies are characterized by a very
      high incidence of the CD22DeltaE12 genetic defect. We provide unprecedented
      experimental evidence for a previously unrecognized causal link between
      CD22DeltaE12 and aggressive biology of BPL cells by demonstrating that siRNA
      mediated knockdown of CD22DeltaE12 in primary BPL cells is associated with a
      marked inhibition of their clonogenicity. These findings provide the preclinical
      proof-of-concept that siRNA-mediated depletion of CD22DeltaE12 may help develop
      effective treatments for high-risk and relapsed BPL patients who are in urgent
      need for therapeutic innovations. We also describe a unique polypeptide-based
      nanoparticle formulation of CD22DeltaE12-siRNA as an RNAi therapeutic candidate
      targeting CD22DeltaE12 that is capable of delivering its siRNA cargo into the
      cytoplasm of leukemia cells causing effective CD22DeltaE12 depletion and marked
      inhibition of leukemic cell growth. Further development and optimization of this
      nanoparticle or other nanoformulation platforms for CD22DeltaE12-siRNA may
      facilitate the development of an effective therapeutic RNAi strategy against
      paradigm shift in therapy of aggressive or chemotherapy-resistant B-lineage
      lymphoid malignancies.

PMID- 25599085
TI  - Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1
      gp120 Impose Immune Pressure on Infecting Viruses.
AB  - To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical
      HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab
      response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic
      V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE
      breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an
      estimated vaccine efficacy of 85% against viruses with amino acids mismatching
      the vaccine at V3 site 317 (p=0.004) and 52% against viruses matching the vaccine
      at V3 site 307 (p=0.004). This analysis was supported by data showing vaccinees'
      plasma Abs were less reactive with I307 replaced with residues found more often
      in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at
      F317 were less infectious, possibly due to the contribution of F317 to optimal
      formation of the V3 hydrophobic core. These data suggest that RV144-induced V3
      specific Abs imposed immune pressure on infecting viruses and inform efforts to
      design an HIV vaccine.

PMID- 25599089
TI  - Obesity-Related Hormones and Metabolic Risk Factors: A Randomized Trial of Diet
      plus Either Strength or Aerobic Training versus Diet Alone in Overweight
      Participants.
AB  - There is debate about the additive effects of exercise in conjunction with diet
      to treat obesity, and not much is known about the differential effects of
      strength versus aerobic training. This randomized controlled trial examined the
      effects of diet plus strength training, diet plus aerobic training, or diet only
      on metabolic risk factors associated with obesity. Eighty-one overweight and
      obese participants completed the 8-week intervention. All participants received
      an energy-restrictive formula diet with an energy content based on 70% of
      measured resting metabolic rate (RMR). Participants assigned to an exercise group
      trained 3 days/week under supervision. Anthropometrics and fasting hormones were
      assessed pre- and post-intervention. Mean weight loss (8.5 +/- 4.3kg SD) did not
      differ between groups nor did reductions in BMI or body fat, although the diet
      plus strength training group showed marginally greater lean mass retention. There
      were significant improvements in the values and number of metabolic syndrome risk
      factors, and decreases in insulin concentrations and insulin resistance, which
      did not vary between groups. For men, testosterone increased significantly more
      in the diet plus aerobic training as compared to the other groups. As compared to
      diet alone, the addition of strength or aerobic training did not improve changes
      in BMI, body fat or metabolic risk factors although the diet plus strength
      training group showed a trend toward preservation of lean mass, and the diet plus
      aerobic group in men resulted in increased testosterone concentrations.

PMID- 25599090
TI  - EBV-Positive Grey Zone Lymphoma in an HIV Infected Man from Kampala, Uganda: Case
      Report.
AB  - AIM: We describe the clinical, histopathological and immunophenotypic
      characteristics of an HIV-infected adult man on antiretroviral therapy who
      presented with an EBV-positive grey zone lymphoma. CASE PRESENTATION: A 56-year
      old HIV infected man from Uganda presented with a four month history of
      progressive abdominal swelling and B-symptoms. He was on highly active
      antiretroviral therapy (HAART) and cotrimoxazole. He was afebrile (36.9 degrees
      C), severely wasted (BMI 14.8), and mildly anaemic. On physical examination, he
      had a 15 by 8 cm mass in the hypogastrium and umbilical region. The total white
      cell count was 8.3*103/MUL; neutrophils, 5.72*103/MUL; haemoglobin 11.1g/dL,
      platelets 528*103/MUL, LDH 197 IU/L and CD4 367/MUL. Abdominal ultrasound and CT
      scan showed a tumour involving the mesentery, jejunum and mid ileum. At
      laparotomy, a biopsy was taken, fixed, processed and stained with Haematoxylin &
      Eosin (H & E). Histopathology demonstrated large pleomorphic cells admixed with
      inflammatory smaller cells, Reed-Sternberg-like cell variants and frequent
      abnormal mitoses. Biomarkers CD20, PAX5, CD30 were positive but ALK negative
      (immunohistochemistry and strong EBER positivity in situ hybridization. The
      patient improved on modified CHOP (cyclophosphamide, doxorubicin, vincristine,
      and prednisolone) therapy. DISCUSSION: The tumour had features intermediate
      between mediastinal large B cell lymphoma and classical Hodgkin lymphoma.
      CONCLUSION: We present a case of EBV-positive grey zone lymphoma in an HIV
      infected man on HAART therapy diagnosed and treated in a resource constrained
      medical setting. The histological features are unusual and represent a low
      incidence lymphoma that is recognized by mixed features reminiscent of Hodgkin's
      lymphoma and mediastinal large B-cell lymphoma.

PMID- 25599091
TI  - The "Family Check Up" in Early Childhood: A Public Health Intervention to Prevent
      Long-term Behavioral and Emotional Disorders.

PMID- 25599088
TI  - Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal
      Seizures in a Mouse Model of Temporal Lobe Epilepsy.
AB  - Temporal lobe epilepsy is often medically refractory and new targets for
      intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line
      seizure detection, and responsive optogenetic intervention to investigate the
      potential for cerebellar control of spontaneous temporal lobe seizures.
      Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures
      during the chronic phase of the disorder. We further report that the direction of
      modulation as well as the location of intervention within the cerebellum can
      affect the outcome of intervention. Specifically, on-demand optogenetic
      excitation or inhibition of parvalbumin-expressing neurons, including Purkinje
      cells, in the lateral or midline cerebellum results in a decrease in seizure
      duration. In contrast, a consistent reduction in spontaneous seizure frequency
      occurs uniquely with on-demand optogenetic excitation of the midline cerebellum,
      and was not seen with intervention directly targeting the hippocampal formation.
      These findings demonstrate that the cerebellum is a powerful modulator of
      temporal lobe epilepsy, and that intervention targeting the cerebellum as a
      potential therapy for epilepsy should be revisited.

PMID- 25599092
TI  - Classification of Alzheimer Diagnosis from ADNI Plasma Biomarker Data.
AB  - Research into modeling the progression of Alzheimer's disease (AD) has made
      recent progress in identifying plasma proteomic biomarkers to identify the
      disease at the pre-clinical stage. In contrast with cerebral spinal fluid (CSF)
      biomarkers and PET imaging, plasma biomarker diagnoses have the advantage of
      being cost-effective and minimally invasive, thereby improving our understanding
      of AD and hopefully leading to early interventions as research into this subject
      advances. The Alzheimer's Disease Neuroimaging Initiative* (ADNI) has collected
      data on 190 plasma analytes from individuals diagnosed with AD as well subjects
      with mild cognitive impairment and cognitively normal (CN) controls. We propose
      an approach to classify subjects as AD or CN via an ensemble of classifiers
      trained and validated on ADNI data. Classifier performance is enhanced by an
      augmentation of a selective biomarker feature space with principal components
      obtained from the entire set of biomarkers. This procedure yields accuracy of 89%
      and area under the ROC curve of 94%.

PMID- 25599087
TI  - The Roles of Primary cilia in Polycystic Kidney Disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic
      disorder that results in progressive renal cyst formation with ultimate loss of
      renal function and other systemic disorders. These systemic disorders include
      abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems.
      ADPKD is considered to be among the ciliopathy diseases due to the association
      with abnormal primary cilia function. In order to understand the full course of
      primary cilia and its association with ADPKD, the structure, functions and role
      of primary cilia have been meticulously investigated. As a result, the focus on
      primary cilia has emerged to support the vital roles of primary cilia in ADPKD.
      The primary cilia have been shown to have not only a mechanosensory function but
      also a chemosensory function. Both structural and functional defects in primary
      cilia result in cystic kidney disease and vascular hypertension. Thus, the
      mechanosenory and chemosensory functions will be analyzed in regards to ADPKD.

PMID- 25599093
TI  - BROWNIAN DYNAMICS SIMULATION OF MACROMOLECULE DIFFUSION IN A PROTOCELL.
AB  - The interiors of all living cells are highly crowded with macromolecules, which
      differs considerably the thermodynamics and kinetics of biological reactions
      between in vivo and in vitro. For example, the diffusion of green fluorescent
      protein (GFP) in E. coli is ~10-fold slower than in dilute conditions. In this
      study, we performed Brownian dynamics (BD) simulations of rigid macromolecules in
      a crowded environment mimicking the cytosol of E. coli to study the motions of
      macromolecules. The simulation systems contained 35 70S ribosomes, 750 glycolytic
      enzymes, 75 GFPs, and 392 tRNAs in a 100 nm * 100 nm * 100 nm simulation box,
      where the macromolecules were represented by rigid-objects of one bead per amino
      acid or four beads per nucleotide models. Diffusion tensors of these molecules in
      dilute solutions were estimated by using a hydrodynamic theory to take into
      account the diffusion anisotropy of arbitrary shaped objects in the BD
      simulations. BD simulations of the system where each macromolecule is represented
      by its Stokes radius were also performed for comparison. Excluded volume effects
      greatly reduce the mobility of molecules in crowded environments for both
      molecular-shaped and equivalent sphere systems. Additionally, there were no
      significant differences in the reduction of diffusivity over the entire range of
      molecular size between two systems. However, the reduction in diffusion of GFP in
      these systems was still 4-5 times larger than for the in vivo experiment. We will
      discuss other plausible factors that might cause the large reduction in diffusion
      in vivo.

PMID- 25599094
TI  - IMPORTANCE OF EXCLUDED VOLUME AND HYDRODYNAMIC INTERACTIONS ON MACROMOLECULAR
      DIFFUSION IN VIVO.
AB  - The interiors of all living cells are highly crowded with macromolecules, which
      results in a considerable difference between the thermodynamics and kinetics of
      biological reactions in vivo from that in vitro. To begin to elucidate the
      principles of intermolecular dynamics in the crowded environment of cells,
      employing Brownian dynamics (BD) simulations, we examined possible mechanism(s)
      responsible for the great reduction in diffusion constants of macromolecules in
      vivo from that at infinite dilution. In an E. coli cytoplasm modelcomprised of 15
      different macromolecule types at physiological concentrations, where
      macromolecules were represented by spheres with their Stokes radii, BD
      simulations were performed with and without hydrodynamic interactions (HI).
      Without HI, the calculated diffusion constant of green fluorescent protein (GFP)
      is much larger than experiment. On the other hand, when HI were considered, the
      in vivo experimental GFP diffusion constant is almost reproduced without
      adjustable parameters. In addition, HI give rise to significant, size independent
      intermolecular dynamic correlations. These results suggest that HI play an
      important role on macromolecular dynamics in vivo.

PMID- 25599096
TI  - Foundational Security Principles for Medical Application Platforms (Extended
      Abstract).
AB  - We describe a preliminary set of security requirements for safe and secure next
      generation medical systems, consisting of dynamically composable units, tied
      together through a real-time safety-critical middleware. We note that this
      requirement set is not the same for individual (stand-alone) devices or for
      electronic health record systems, and we must take care to define system-level
      requirements rather than security goals for components. The requirements
      themselves build on each other such that it is difficult or impossible to
      eliminate any one of the requirements and still achieve high-level security
      goals.

PMID- 25599097
TI  - Determining a Blind Pedestrian's Location and Orientation at Traffic
      Intersections.
AB  - This paper describes recent progress on Crosswatch, a smartphone-based computer
      vision system developed by the authors for providing guidance to blind and
      visually impaired pedestrians at traffic intersections. One of Crosswatch's key
      capabilities is determining the user's location (with precision much better than
      what is obtainable by GPS) and orientation relative to the crosswalk markings in
      the intersection that he/she is currently standing at; this capability will be
      used to help him/her find important features in the intersection, such as walk
      lights, pushbuttons and crosswalks, and achieve proper alignment to these
      features. We report on two new contributions to Crosswatch: (a) experiments with
      a modified user interface, tested by blind volunteer participants, that makes it
      easier to acquire intersection images than with previous versions of Crosswatch;
      and (b) a demonstration of the system's ability to localize the user with
      precision better than what is obtainable by GPS, as well as an example of its
      ability to estimate the user's orientation.

PMID- 25599095
TI  - 5. T cell immunity and neuroplasticity.
AB  - The proneuronal effects of T cells that impact the brain occur from both T cells
      trafficking into the brain, and from signals in the periphery (e.g., cytokine
      release and regulation). Recent data indicates that neuroimmunological changes in
      the brain can modify intrinsic brain processes that are involved in regulating
      neuroplasticity (e.g., T-cell/microglial interactions, neurotrophins,
      neurogenesis). We describe: 1) work from our lab and others showing that injury
      induced loss of neuronal phenotype and reversal of motor neuron atrophy are
      associated with normal T cell immunity, and; 2) research indicating that these
      and other neuroimmunological processes may be generalizable to mechanisms of
      neuroplasticity involved in cognitive and emotional behavior. These findings are
      discussed in relation to our lab's working hypothesis, that T cell
      immunosenesence may contribute to alterations in brain neuroplasticity related to
      aging. Greater understanding of the role of adaptive T cell immunity on
      neuroplasticity could have important clinical implications for developing novel
      treatment strategies for neurodegenerative diseases (e.g., Alzheimer's) and brain
      injury (e.g., stroke, trauma).

PMID- 25599098
TI  - Design and application of an open tubular capillary reactor for solid-phase
      permethylation of glycans in glycoprotein.
AB  - The permethylation derivatization method for structural analysis of glycans is
      important for characterizing glycoproteins in the study of glycomics. An open
      tubular capillary reactor coated with NaOH was designed and constructed for solid
      phase permethylation of glycans in glycoproteins. The flow rate, capillary
      length, and inner diameter of the reactor were optimized. The permethylation rate
      of the model sample beta-cyclodextrin reached 81% with a flow rate of 1 MUL min(
      1) in a 32 cm long capillary reactor (i.d. 500 MUm). A trace amount of mucin O
      glycans was permethylated by the open tubular reactor under low pressure without
      interference from the freezing of DMSO. Analysis indicates that using this open
      tubular reactor is a fast, convenient, and efficient method for the
      permethylation of protein O-glycan. 

PMID- 25599099
TI  - Focus-independent particle size measurement from streak images: a comparison of
      multivariate methods.
AB  - Our laboratories have recently developed a flow-through imaging photometer to
      characterize and classify fluorescent particles between 3 and 47 MUm in size. The
      wide aperture of the objective lens (0.7 NA) required for measuring spectral
      fluorescence of single particles restricts the depth of field, such that a large
      sample volume results in many particles that are out of focus. Here, we describe
      numerical methods for determining the size of these objects, regardless of their
      distance from the focal plane, using image processing and multivariate
      calibration. An intensity profile is extracted from the images and is used as the
      input for a variety of calibration methods, including partial least squares,
      neural networks, and support vector machines. The capabilities of these methods
      are examined to establish the best method for particle sizing that is independent
      of focus. We found that support vector machines provided the best results, with
      size estimation error of +/-3.1 MUm. 

PMID- 25599100
TI  - A single-step enzyme immunoassay capillary sensor composed of functional
      multilayer coatings for the diagnosis of marker proteins.
AB  - A single-step, easy-to-use enzyme immunoassay capillary sensor, composed of
      functional multilayer coatings, was developed in this study. The coatings were
      composed of substrate-immobilized hydrophobic coating, hydrogel coating, and
      soluble coating containing an enzyme-labeled antibody. The response mechanism
      involved a spontaneous immunoreaction triggered by capillary action-mediated
      introduction of a sample antigen solution and subsequent separation of unreacted
      enzyme-labeled antibodies and antigen-enzyme-labeled antibody complexes by the
      molecular sieving effect of the hydrogel. An enzyme reaction at the substrate
      immobilized hydrophobic coating/hydrogel coating interface resulted in a protein
      selective fluorescence response. An antigen concentration-dependent response was
      obtained for diagnostic marker protein samples (hemoglobin A1c (HbA1c), 7.14-16.7
      mg mL(-1); alpha-fetoprotein (AFP), 1.4-140 ng mL(-1); C-reactive protein (CRP),
      0.5-10 MUg mL(-1)) that cover a clinically important concentration range. The
      successful measurement of CRP in diluted serum samples demonstrated the
      application of this capillary sensor. 

PMID- 25599101
TI  - Identification of spectral biomarkers for type 1 diabetes mellitus using the
      combination of chiroptical and vibrational spectroscopy.
AB  - The current diagnostic tools are insufficient for the early detection of many
      diseases, including type 1 diabetes mellitus. The disease is accompanied not only
      by a permanently elevated level of blood glucose and altered levels of other
      biomarkers, but also by changes in the conformation of blood plasma proteins and
      other biomolecules associated with the pathogenesis of diabetes. However, the
      observation of these structural changes by conventional Raman and infrared
      spectroscopy is limited. Therefore, we used chiroptical spectroscopy which is
      inherently sensitive to the 3D structure of chiral molecules and able to detect
      any possible structural changes. We investigated the blood plasma samples of
      diabetic patients and healthy controls by Raman optical activity and electronic
      circular dichroism. The measurements were combined with conventional methods of
      molecular spectroscopy, i.e. Raman and infrared spectroscopy. The obtained data
      sets were statistically evaluated using linear discriminant analysis focusing on
      the spectral ranges that correspond to the structure and conformation of proteins
      and other plasmatic biomolecules. Our results suggest that chiroptical
      spectroscopy gives more detailed information about the 3D structure of
      biomolecules; and therefore, might be a promising complement to conventional
      diagnostic methods. 

PMID- 25599102
TI  - Nuclear accumulation of anthracyclines in the endothelium studied by bimodal
      imaging: fluorescence and Raman microscopy.
AB  - Anthracycline antibiotics display genotoxic activity towards cancer cells but
      their clinical utility is limited by their cardiac and vascular toxicity. The aim
      of this study was to develop a Raman-based methodology to study the nuclear
      accumulation of anthracyclines in the endothelium. For this purpose bimodal
      confocal Raman and fluorescence imaging was used to monitor cellular composition
      changes as a result of anthracycline exposure on endothelial cells (EA.hy926),
      and nuclear drug accumulation, respectively. Simultaneously effects of
      anthracyclines on endothelium viability were investigated by caspases-3 and -7
      and MTT assays. We demonstrated that nuclear accumulation of DOX and EDOX was
      similar; however, EDNR accumulated in endothelial nuclei at concentrations 10
      times higher than DNR. In turn, epimers of DOX or DNR were both consistently less
      toxic on the endothelium as compared to their congeners as evidenced by MTT and
      caspase assays. In summary, bimodal Raman and fluorescence-based nucleus
      profiling proves to be a valuable tool to study structure-activity relationship
      of nuclear accumulation and toxicity of anthracyclines in endothelium. 

PMID- 25599103
TI  - Specific in situ hepatitis B viral double mutation (HBVDM) detection in urine
      with 60 copies ml(-1) analytical sensitivity in a background of 250-fold wild
      type without DNA isolation and amplification.
AB  - We have examined in situ detection of hepatitis B virus 1762T/1764A double
      mutation (HBVDM) in urine using a (Pb(Mg(1/3)Nb(2/3))O3)(0.65)(PbTiO3)(0.35) (PMN
      PT) piezoelectric plate sensor (PEPS) coated with a 16-nucleotide (nt) probe DNA
      (pDNA) complementary to the HBVDM. The in situ mutation (MT) detection was
      carried out in a flow with the PEPS vertically situated at the center of the flow
      in a background of wild type (WT). For validation, this detection was followed by
      detection in the mixture of MT fluorescent reporter microspheres (FRMs) (MT FRMs)
      and WT FRMs that emitted different fluorescence colours and were designed to
      specifically bind to MT and WT, respectively. At 30  degrees C and 4 ml min(-1),
      a PEPS was shown to specifically detect HBVDM in situ with 60 copies ml(-1)
      analytical sensitivity in a background of clinically-relevant 250-fold more WT in
      30 min without DNA isolation, amplification, or labelling as validated by the
      visualization of the captured MT FRMs and WT FRMs following FRM detection where
      the captured MT FRMs outnumbered the WT FRMs by a factor of 5 to 1.

PMID- 25599104
TI  - Online SERS detection and characterization of eight biologically-active peptides
      separated by capillary zone electrophoresis.
AB  - There is a need for low cost, sensitive and chemical specific detectors for
      routine characterization of biomolecules. In this study, we utilize sheath-flow
      surface-enhanced Raman scattering (SERS) to analyze a mixture of eight
      biologically-active peptides separated by capillary zone electrophoresis (CZE).
      Analysis of the SERS electropherogram resulting from online detection resolves
      the characteristic Raman bands attributed to the amino acid constituents of each
      peptide, which enables identification. The detection limit by SERS was found to
      be 10(-8) M. Our results suggest that the structural information obtained from
      the detected vibrational modes provides complementary characterization to other
      chemically specific detectors like mass spectrometry and improved chemical
      identification over other commonly used optical-based post-chromatographic
      detection methods. In addition, the sheath-flow SERS detection results in band
      narrowing in the observed electropherogram that enables distinction of closely
      migrating species. The results presented here indicate that this platform can
      provide fast, robust, reproducible, and chemical specific detection to facilitate
      the characterization of peptides. 

PMID- 25599105
TI  - The "sweet" side of the protein corona: effects of glycosylation on nanoparticle
      cell interactions.
AB  - The significance of a protein corona on nanoparticles in modulating particle
      properties and their biological interactions has been widely acknowledged. The
      protein corona is derived from proteins in biological fluids, many of which are
      glycosylated. To date, the glycans on the proteins have been largely overlooked
      in studies of nanoparticle-cell interactions. In this study, we demonstrate that
      glycosylation of the protein corona plays an important role in maintaining the
      colloidal stability of nanoparticles and influences nanoparticle-cell
      interactions. The removal of glycans from the protein corona enhances cell
      membrane adhesion and cell uptake of nanoparticles in comparison with the fully
      glycosylated form, resulting in the generation of a pro-inflammatory milieu by
      macrophages. This study highlights that the post-translational modification of
      proteins can significantly impact nanoparticle-cell interactions by modulating
      the protein corona properties. 

PMID- 25599106
TI  - Plant functional traits predict green roof ecosystem services.
AB  - Plants make important contributions to the services provided by engineered
      ecosystems such as green roofs. Ecologists use plant species traits as generic
      predictors of geographical distribution, interactions with other species, and
      ecosystem functioning, but this approach has been little used to optimize
      engineered ecosystems. Four plant species traits (height, individual leaf area,
      specific leaf area, and leaf dry matter content) were evaluated as predictors of
      ecosystem properties and services in a modular green roof system planted with 21
      species. Six indicators of ecosystem services, incorporating thermal,
      hydrological, water quality, and carbon sequestration functions, were predicted
      by the four plant traits directly or indirectly via their effects on aggregate
      ecosystem properties, including canopy density and albedo. Species average height
      and specific leaf area were the most useful traits, predicting several services
      via effects on canopy density or growth rate. This study demonstrates that easily
      measured plant traits can be used to select species to optimize green roof
      performance across multiple key services. 

PMID- 25599107
TI  - Stability of executive functioning measures in 8-17-year-old children with
      unilateral cerebral palsy.
AB  - The study investigated the stability of executive functioning (EF) measures in
      children and adolescents aged 8-17 years with unilateral cerebral palsy (CP).
      Here 44 participants with unilateral CP (mean age = 11 years, 11 months; Manual
      Abilities Classification Scale Level I = 6 and Level II = 37; Gross Motor
      Function Classification Scale Level I = 22 and Level II = 22) were randomized
      into the wait-list control group of a large randomized controlled trial.
      Participants had baseline testing with Wechsler Intelligence Scale for Children-
      Fourth Edition Short Form (WISC-IV-SF) and Delis-Kaplan Executive Function System
      (D-KEFS) subtests. Parents completed the Behavior Rating Inventory of Executive
      Functioning (BRIEF). Participants were re-assessed 20 +/-2 weeks later with a
      shortened test battery including the D-KEFS subtests; Digit Span, Coding and
      Symbol Search (WISC-IV); and BRIEF. Pearson's test-retest reliabilities and
      Reliable change scores were calculated. Results indicated excellent to fair test
      retest reliabilities (r = 0.91-0.74) for all measures except Digit Span Backwards
      (r = 0.62), Inhibition (r = 0.69), and Initiate (r = 0.68). Reliable change
      scores applying 90% confidence intervals for estimating reliable change while
      accounting for practice effects were provided for all measures. The data support
      the stability of EF measures in this population.

PMID- 25599108
TI  - Psychometric properties of the Florence CyberBullying-CyberVictimization Scales.
AB  - The present study tried to answer the research need for empirically validated and
      theoretically based instruments to assess cyberbullying and cybervictimization.
      The psychometric properties of the Florence CyberBullying-CyberVictimization
      Scales (FCBVSs) were analyzed in a sample of 1,142 adolescents (Mage=15.18 years;
      SD=1.12 years; 54.5% male). For both cybervictimization and cyberbullying,
      results support a gender invariant model involving 14 items and four factors
      covering four types of behaviors (written-verbal, visual, impersonation, and
      exclusion). The second-order confirmatory factor analysis confirmed that a
      "global," second-order measure of cyberbullying and cybervictimization fits the
      data well. Overall, the scales showed good validity (construct, concurrent, and
      convergent) and reliability (internal consistency and test-retest). In addition,
      using the global key question measure as a criterion, ROC analyses, determining
      the ability of a test to discriminate between groups, allowed us to identify
      cutoff points to classify respondents as involved/not involved starting from the
      continuum measure derived from the scales. 

PMID- 25599109
TI  - Effect of Loading Dose of Dexmedetomidine on Dynamic Cerebral Blood Flow
      Autoregulation in Patients With Intracranial Glial Neoplasms.
AB  - BACKGROUND: Dexmedetomidine has been widely used in neuroanesthesia and critical
      care settings. The effects of dexmedetomidine on cerebral vascular autoregulation
      and hemodynamics in patients with intracranial pathology are not well defined.
      This study is aimed to address this issue. METHODS: Fifteen patients with
      unilateral supratentorial glial tumor (group S) and 15 patients without any
      intracranial pathology (group C) were included in this study. Transient hyperemic
      response testing was conducted bilaterally in both groups with transcranial color
      Doppler. Dynamic autoregulation was assessed with transient hyperemic response
      ratio (THRR) and strength of autoregulation (SA) at baseline and after infusion
      of inj. dexmedetomidine (1 mcg/kg) over 10 minutes. RESULTS: THRR and SA values
      in the hemisphere that had tumor (group S) showed no difference from baseline
      after a loading dose of dexmedetomidine (P=0.914, 0.217). In the nontumor
      hemisphere of group S and in both the hemispheres of group C, significant
      reduction in THRR and SA values were observed (P<0.001) after administration of a
      loading dose of dexmedetomidine. THRR values were higher in the tumor hemisphere
      when compared with the nonpathologic hemispheres (P<0.001), suggesting the
      possibility of baseline hyperemia. CONCLUSIONS: In the hemisphere that had glial
      tumor, autoregulatory indices showed no significant change after dexmedetomidine.
      It can be because of abnormal vascular architecture and its altered reactivity to
      dexmedetomidine, or because of baseline hyperemia itself, but the exact mechanism
      needs to be elucidated. In the nonpathologic hemispheres, THRR and SA values were
      decreased, suggesting impaired autoregulation with the use of loading dose of
      dexmedetomidine.

PMID- 25599110
TI  - Changes in Physical Activity Domains During the Transition Out of High School:
      Psychosocial and Environmental Correlates.
AB  - BACKGROUND: This study examined changes in multiple physical activity domains
      during the transition out of high school and psychosocial and environmental
      determinants of these changes. METHODS: A 1-year prospective study was designed.
      The baseline sample was composed of 244 last-year high school students (58.6%
      female) from Valencia, Spain. Follow-up rate was 46%. Physical activity and
      potential determinants were measured by the Global Physical Activity
      Questionnaire and other evaluated scales in 2 waves. RESULTS: Total physical
      activity and active commuting (AC) decreased, respectively, by 21% and 36%, only
      in males. At time 1, access to car/motorbike (inverse), planning/psychosocial
      barriers (inverse), street connectivity (positive) and parental education
      (inverse) were significantly associated with AC (P < .05). Prospectively, the
      increase in distance to school/workplace was associated with AC decrease among
      males (P < .001). In both genders, there was a decrease in leisure-time physical
      activity (LTPA; -35% in males, -43% in females). At time 1, self-efficacy and
      social support were positive correlates of LTPA (P < .05). Social support
      decreases were associated with reductions in LTPA for males (P < .05).
      CONCLUSIONS: Several psychosocial and environmental correlates of physical
      activity change were identified, and these are promising targets for
      interventions.

PMID- 25599111
TI  - Systematic Review and Meta-Analysis of Multi-Component Interventions Through
      Schools to Increase Physical Activity.
AB  - BACKGROUND: A "whole-of-school" approach is nationally endorsed to increase youth
      physical activity (PA). Aligned with this approach, comprehensive school physical
      activity programs (CSPAP) are recommended. Distinct components of a CSPAP include
      physical education (PE), PA during the school day (PADS), PA before/after school
      (PABAS), staff wellness (SW), and family/community engagement (FCE). The
      effectiveness of interventions incorporating multiple CSPAP components is
      unclear. A systematic review and meta-analysis were conducted examining the
      effectiveness of multicomponent interventions on youth total daily PA. METHODS:
      Electronic databases were searched for published studies that (1) occurred in the
      US; (2) targeted K-12 (5-18 years old); (3) were interventions; (4) reflected >=
      2 CSPAP components, with at least 1 targeting school-based PA during school
      hours; and (5) reported outcomes as daily PA improvements. Standardized mean
      effects (Hedge's g) from pooled random effects inverse-variance models were
      estimated. RESULTS: Across 14 studies, 12 included PE, 5 PADS, 1 PABAS, 2 SW, and
      14 FCE. No studies included all 5 CSPAP components. Overall, intervention impact
      was small (0.11, 95% CI 0.03-0.19). CONCLUSIONS: As designed, there is limited
      evidence of the effectiveness of multicomponent interventions to increase youth
      total daily PA. Increased alignment with CSPAP recommendations may improve
      intervention effectiveness.

PMID- 25599113
TI  - Kganya Motsha Adolescent Centre: a model for adolescent friendly HIV management
      and reproductive health for adolescents in Soweto, South Africa.
AB  - This paper reports on Kganya Motsha Adolescent Centre, an adolescent program
      specifically established to provide voluntary counseling and testing as well as
      management of HIV-positive young people in Soweto, South Africa. A retrospective
      cross-sectional analysis, using clinic records of young people accessing services
      from 2008 to 2012, was conducted. Of the 11,522 who tested, 7689 (67%) were
      females. The total number of HIV infections was 410, with an HIV prevalence of
      3.6% (95% CI 3.2-3.9%). More females (332, 4% vs. 72, 2%; p < 0.0001) were HIV
      infected than males. Of those testing HIV positive, 109 (26.5%) had a median CD4
      cell count of 491 (IQR 345-686) cells/mm(3). Only 12/410 individuals (2.9%) were
      eligible for antiretroviral treatment and 10 (2.4%) of those successfully
      received treatment. The program observed that young people testing HIV positive
      would not return for follow up blood specimens or confirmatory results. Future
      programs should consider innovative ways of retaining adolescents in care to
      reduce potential HIV transmissions that could lead to deteriorating health. 

PMID- 25599112
TI  - Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation
      Induced by Freund's Complete Adjuvant in Rats.
AB  - One of the major mechanisms in the pathogenesis of chronic inflammation is the
      excessive production of reactive oxygen and reactive nitrogen species, and
      therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked
      antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity
      in certain experimental models, the latter activity being mediated probably by
      the antioxidant activity of this cyanobacterium. In the present study, chronic
      inflammation was induced through injection of Freund's complete adjuvant (CFA) in
      rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on
      day 14. Joint diameter, body temperature, and motor capacity were assessed each
      week. On days 0 and 28, total and differential leukocyte counts and serum
      oxidative damage were determined, the latter by assessing lipid peroxidation and
      protein carbonyl content. At the end of the study, oxidative damage to joints was
      likewise evaluated. Results show that S. maxima favors increased mobility, as
      well as body temperature regulation, and a number of circulating leukocytes,
      lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and
      also protects against oxidative damage in joint tissue as well as serum. In
      conclusion, the protection afforded by S. maxima against development of chronic
      inflammation is due to its antioxidant activity. 

PMID- 25599114
TI  - Fabrication of hydrophilic polymer nanocontainers by use of supramolecular
      templates.
AB  - Polymer-shelled vesicles are prepared by using cyclodextrin vesicles as
      supramolecular templates and an adamantane-functionalized poly(acrylic acid)
      additive anchored via host-guest recognition, followed by cross-linking of
      carboxylic acid groups on the polymer. The polymer-shelled nanocontainers are
      highly stable and effective for encapsulating small hydrophilic molecules. We
      also show that a hollow cross-linked polymer cage can be obtained after
      dissolution of the template vesicles. The size and shell thickness of the polymer
      cage can be tuned by variation of template size and polymer length. 

PMID- 25599116
TI  - Tuning the mobility coupling of quaternized polyvinylpyridine and anionic
      phospholipids in supported lipid bilayers.
AB  - Binding of biomacromolecules to anionic lipids in the plasma membrane is a common
      motif in many cell signaling pathways. Previous work has shown that
      macromolecules with cationic sequences can form nanodomains with sequestered
      anionic lipids, which alters the lateral distribution and mobility of the
      membrane lipids. Such sequestration is believed to result from the formation of a
      lipid-macromolecule complex. To date, however, the molecular structure and
      dynamics of the lipid-polymer interface are poorly understood. We have
      investigated the behavior of polycationic quaternized polyvinylpyridine (QPVP) on
      supported lipid bilayers doped with phosphatidylserine (PS) or
      phosphatidylinositol phosphate (PIP) lipids using time-resolved fluorescence
      microscopy, including pulsed interleaved excitation fluorescence cross
      correlation spectroscopy (PIE-FCCS). PIE-FCCS is a dual-color fluorescence
      spectroscopy that translates fluctuations in fluorescence signal into a
      measurement of diffusion and colocalization. By labeling the polymer and lipids,
      we investigated the adsorption-induced translational mobility of lipids and
      systematically studied the influence of lipid charge density and solution ionic
      strength. Our results show that alteration of anionic lipid lateral mobility is
      dependent on the net charge of the lipid headgroup and is modulated by the ionic
      strength of the solution, indicating that electrostatic interactions drive the
      decrease in lateral mobility of anionic lipids by adsorbed QPVP. At physiological
      salt concentration we observe that the lipid lateral mobility is weakly
      influenced by QPVP and that there is no evidence of stable lipid-polymer
      complexes. 

PMID- 25599117
TI  - Letter to the editor concerning the article "Effects of acoustic feedback
      training in elite-standard Para-Rowing" by Schaffert and Mattes (2015).
AB  - In a case study, Schaffert and Mattes reported the application of acoustic
      feedback (sonification) to optimise the time course of boat acceleration. The
      authors attributed an increased boat speed in the feedback condition to an
      optimised boat acceleration (mainly during the recovery phase). However, in
      rowing it is biomechanically impossible to increase the boat speed significantly
      by reducing the fluctuations in boat acceleration during the rowing cycle. To
      assess such a, potentially small, optimising effect experimentally, the
      confounding variables must be controlled very accurately (that is especially the
      propulsive forces must be kept constant between experimental conditions or the
      differences in propulsive forces between conditions must be much smaller than the
      effects on boat speed resulting from an optimised movement pattern). However,
      this was not controlled adequately by the authors. Instead, the presented boat
      acceleration data show that the increased boat speed under acoustic feedback was
      due to increased propulsive forces. 

PMID- 25599115
TI  - Posttraumatic stress and depression: potential pathways to disease burden among
      heart failure patients.
AB  - BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder (PTSD) and Major
      Depressive Disorder (MDD) are associated with high disease burden. Pathways by
      which PTSD and MDD contribute to disease burden are not understood. DESIGN: Path
      analysis was used to examine pathways between PTSD symptoms, MDD symptoms, and
      disease burden among 251 low-income heart failure patients. METHODS: In Model 1,
      we explored the independent relationship between PTSD and MDD symptoms on disease
      burden. In Model 2, we examined the association of PTSD symptoms and disease
      burden on MDD symptoms. We also examined indirect associations of PTSD symptoms
      on MDD symptoms, mediated by disease burden, and of PTSD symptoms on disease
      burden mediated by MDD symptoms. RESULTS: Disease burden correlated with PTSD
      symptoms (r = .41; p < .001) and MDD symptoms (r = .43; p < .001) symptoms. Both
      models fit the data well and displayed comparable fit. MDD symptoms did not
      mediate the association of PTSD symptoms with disease burden. Disease burden did
      mediate the relationship between PTSD symptoms and MDD symptoms. CONCLUSIONS:
      Results support the importance of detection of PTSD in individuals with disease.
      Results also provide preliminary models for testing longitudinal data in future
      studies.

PMID- 25599118
TI  - A bioinspired multi-modal flying and walking robot.
AB  - With the aim to extend the versatility and adaptability of robots in complex
      environments, a novel multi-modal flying and walking robot is presented. The
      robot consists of a flying wing with adaptive morphology that can perform both
      long distance flight and walking in cluttered environments for local exploration.
      The robot's design is inspired by the common vampire bat Desmodus rotundus, which
      can perform aerial and terrestrial locomotion with limited trade-offs. Wings'
      adaptive morphology allows the robot to modify the shape of its body in order to
      increase its efficiency during terrestrial locomotion. Furthermore, aerial and
      terrestrial capabilities are powered by a single locomotor apparatus, therefore
      it reduces the total complexity and weight of this multi-modal robot. 

PMID- 25599119
TI  - Feasibility and Preliminary Efficacy of the MADE4Life Program: A Pilot Randomized
      Controlled Trial.
AB  - BACKGROUND: The aim was to assess the feasibility and preliminary efficacy of a
      community-based physical activity (PA) intervention targeting mothers and
      daughters. METHODS: A randomized controlled trial of 48 primary school-aged girls
      and their 40 mothers were randomized to (i) Mothers And Daughters Exercising for
      Life (MADE4Life) (n = 21 mothers, n = 25 daughters) or (ii) wait-list control (n
      = 19 mothers, n = 23 daughters). The 8-week program involved 8 sessions; 25
      minute separate mothers and daughters education sessions and 60-minutes PA
      together. Assessments were at baseline, postintervention and 3-month
      postintervention. Primary outcome measure was daughters' moderate-to- vigorous
      physical activity (MVPA) (accelerometer). Secondary outcomes included
      accelerometer-assessed light/moderate/vigorous PA, BMI, waist circumference, body
      composition, blood pressure, resting heart rate, sedentary behaviors and mothers'
      self-reported PA, parenting measures, and cognitions. Intention-to-treat analysis
      used linear mixed models. RESULTS: Recruitment and retention goals were exceeded.
      Attendance rates, program acceptability and satisfaction were high. There was no
      significant group-by-time effect for daughters' %MVPA (-0.08; 95%CI -1.49, 1.33,
      d = -0.03) or other secondary outcomes for girls (postintervention range d = 0.01
      to -0.46). Significant intervention effects were found for mothers' %VPA (P =
      .04, d = 0.25) and role modeling (P = .02, d = 0.66). CONCLUSION: MADE4Life was
      both feasible and acceptable. Although very small effect sizes were found for the
      daughters, significant changes were seen for mothers (d = 0.25 to 0.66). Future
      fully powered trials targeting PA in mothers and daughters is warranted.

PMID- 25599122
TI  - Effect of different temporary crown materials and surface roughening methods on
      the shear bond strengths of orthodontic brackets.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of different
      temporary crown materials (TCMs) and surface roughening methods on the shear bond
      strength (SBS) of orthodontic brackets. BACKGROUND DATA: TCMs are widely used
      during orthodontic treatment in teeth in need of prosthetic treatment, to prevent
      damage to the final restoration. However, there is no consensus considering the
      best method for roughening of the surface of TCMs. METHODS: Five different TCMs
      [Dentalon Plus-(D), Basworth Trim II-(B), Voco Structure Premium-(V), 3M ESPE
      Protempt 4-(P), and Revotek LC-(R)] were used in this study. Different surface
      roughening methods (37% phosphoric acid, sandblasting, and Er:YAG laser) were
      employed in three subgroups (n=20). The SBS test was used to assess the
      durability of all groups. Scanning electron microscopy (SEM) analysis was
      performed on a representative specimen in each group. RESULTS: The highest mean
      SBS value was observed in group V, followed by groups D and P, regardless of the
      surface treatment. The lowest SBS values were observed in group B. The laser
      irradiated groups had higher SBS values than the sandblasted and acid-etched
      groups. Furthermore, a significant difference in SBS values was observed between
      the laser-irradiated group V and all other groups (p<0.005). CONCLUSIONS: The
      effects of the chemical nature of TCMs on the SBS values appeared to be
      clinically negligible, whereas the type of surface treatments had a significant
      influence on bond strengths. Er:YAG laser irradiation caused a significant
      increase in bond strength between the TCMs and orthodontic brackets.

PMID- 25599121
TI  - Cancer incidence, trends, and survival among immigrants to Sweden: a population
      based study.
AB  - This review aimed at covering cancer risk trends by site and histology in first
      generation and second-generation immigrants in Sweden compared with natives. In
      addition, we reviewed data on cancer survival in immigrants to explore factors
      explaining cancer survival in the entire population. The Swedish Family-Cancer
      Database was used to calculate standardized incidence ratios and hazard ratios
      (HRs) of death from cancer in 77,360 and 993,824 cases among first-generation,
      and 4356 and 263,485 cases among second-generation immigrants and Swedes,
      respectively. Ordinal logistic regression analyses were used to calculate odds
      ratio. To obtain the maximum number of cases, we classified the immigrants
      according to geographical setting, population, and/or cancer risk. Compared with
      native Swedes, the highest risk of cancer was observed for nasopharyngeal
      carcinoma in Southeast Asian men (standardized incidence ratio=35.6) and women
      (24.6), for hypopharyngeal carcinoma in Indian men (5.4), for squamous-cell
      carcinoma of the esophagus in Iranian women (3.8), for cardia of the stomach in
      East Asian women (4.2), for signet-ring cell carcinoma of the stomach in
      Southeast Asian women (6.7), for the liver in East Asian men (6.8), for the gall
      bladder in Indian women (3.8), for the pancreas in North African men (2.2), for
      large cell carcinoma of the lung in former Yugoslavian men (4.2), for pleural
      mesothelioma in Turkish women (23.8), for the cervix in Danes (1.6), for seminoma
      in Chileans (2.1), for transitional-cell carcinoma of the bladder in Asian Arab
      men (2.3), for meningioma in former Yugoslavians (1.3), and for papillary
      carcinoma of the thyroid in East and Southeast Asian men (3.6). No immigrant
      groups had an increased risk of breast, uterus, ovary, and prostate cancers or
      nervous system tumors. The HRs for all breast cancers were between 1.0 in low
      risk Europeans and 1.2 in lowest-risk non-Europeans. Low-risk non-Europeans had
      an HR of 2.9 for lobular carcinoma. Low-risk non-Europeans were diagnosed in a
      higher T-class (odds ratio=1.9) than Swedes. The HRs for prostate cancer were 0.6
      in Turks, Middle Easterners, Asians, and Chileans. In conclusion, environmental
      and behavioral factors, early-childhood exposures, and infections may play a
      major role in the risk of esophageal, stomach, liver, nasopharyngeal and
      hypopharyngeal cancers, malignant pleural mesothelioma, breast, gynecological,
      testicular, urinary bladder, and thyroid cancers. Pancreatic cancer and nervous
      system tumors may have a major genetic component in the etiology. The ethnic
      differences in the risk of breast cancer by histology had no major influence on
      survival. Middle Easterners, Asians, and Chileans, with the lowest risk of
      prostate cancer, also had the most favorable survival, suggesting a biological
      mechanism for this finding.

PMID- 25599120
TI  - Dietary sodium content, mortality, and risk for cardiovascular events in older
      adults: the Health, Aging, and Body Composition (Health ABC) Study.
AB  - IMPORTANCE: Additional information is needed about the role of dietary sodium on
      health outcomes in older adults. OBJECTIVE: To examine the association between
      dietary sodium intake and mortality, incident cardiovascular disease (CVD), and
      incident heart failure (HF) in older adults. DESIGN, SETTING, AND PARTICIPANTS:
      We analyzed 10-year follow-up data from 2642 older adults (age range, 71-80
      years) participating in a community-based, prospective cohort study (inception
      between April 1, 1997, and July 31, 1998). EXPOSURES: Dietary sodium intake at
      baseline was assessed by a food frequency questionnaire. We examined sodium
      intake as a continuous variable and as a categorical variable at the following
      levels: less than 1500 mg/d (291 participants [11.0%]), 1500 to 2300 mg/d (779
      participants [29.5%]), and greater than 2300 mg/d (1572 participants [59.5%]).
      MAIN OUTCOMES AND MEASURES: Adjudicated death, incident CVD, and incident HF
      during 10 follow-up years. Analysis of incident CVD was restricted to 1981
      participants without prevalent CVD at baseline. RESULTS: The mean (SD) age of
      participants was 73.6 (2.9) years, 51.2% were female, 61.7% were of white race,
      and 38.3% were black. After 10 years, 881 participants had died, 572 had
      developed CVD, and 398 had developed HF. In adjusted Cox proportional hazards
      regression models, sodium intake was not associated with mortality (hazard ratio
      [HR] per 1 g, 1.03; 95% CI, 0.98-1.09; P = .27). Ten-year mortality was
      nonsignificantly lower in the group receiving 1500 to 2300 mg/d (30.7%) than in
      the group receiving less than 1500 mg/d (33.8%) and the group receiving greater
      than 2300 mg/d (35.2%) (P = .07). Sodium intake of greater than 2300 mg/d was
      associated with nonsignificantly higher mortality in adjusted models (HR vs 1500
      2300 mg/d, 1.15; 95% CI, 0.99-1.35; P = .07). Indexing sodium intake for caloric
      intake and body mass index did not materially affect the results. Adjusted HRs
      for mortality were 1.20 (95% CI, 0.93-1.54; P = .16) per milligram per
      kilocalorie and 1.11 (95% CI, 0.96-1.28; P = .17) per 100 mg/kg/m2 of daily
      sodium intake. In adjusted models accounting for the competing risk for death,
      sodium intake was not associated with risk for CVD (subHR per 1 g, 1.03; 95% CI,
      0.95-1.11; P = .47) or HF (subHR per 1 g, 1.00; 95% CI, 0.92-1.08; P = .92). No
      consistent interactions with sex, race, or hypertensive status were observed for
      any outcome. CONCLUSIONS AND RELEVANCE: In older adults, food frequency
      questionnaire-assessed sodium intake was not associated with 10-year mortality,
      incident CVD, or incident HF, and consuming greater than 2300 mg/d of sodium was
      associated with nonsignificantly higher mortality in adjusted models.

PMID- 25599123
TI  - Orally administered indomethacin acutely reduces cellular prion protein in the
      small intestine and modestly increases survival of mice exposed to infectious
      prions.
AB  - OBJECTIVE: The oral uptake of infectious prions represents a common way to
      acquire a prion disease; thus, host factors, such as gut inflammation and
      intestinal "leakiness", have the potential to influence infectivity. For example,
      the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to induce
      intestinal inflammation and increase intestinal permeability. Previously, we
      reported that normal cellular prion protein (PrP(C)) expression was increased in
      experimental colitis, and since the level of PrP(C) expressed is a determinant of
      prion disease propagation, we hypothesized that NSAID administration prior to the
      oral inoculation of mice with infectious prions would increase intestinal PrP(C)
      expression and accelerate the onset of neurological disease. MATERIALS AND
      METHODS: In the long-term experiments, one group of mice was gavaged with
      indomethacin, followed by a second gavage with brain homogenate containing mouse
      adapted scrapie (ME7). Control mice received ME7 brain homogenate alone. Brain
      and splenic tissues were harvested at several time points for immunoblotting,
      including at the onset of clinical signs of disease. In a second series of
      experiments, mice were gavaged with indomethacin to assess the acute effects of
      this treatment on intestinal PrP(C) expression. RESULTS: Acutely, NSAID treatment
      reduced intestinal PrP(C) expression, and chronically, there was a modest delay
      in the onset of neurological disease. CONCLUSION: In contrast to our hypothesis,
      brief exposure to an NSAID decreased intestinal PrP(C) expression and led to a
      modest survival advantage following oral ingestion of infectious prions.

PMID- 25599124
TI  - Immunohistochemistry-based prognostic biomarkers in NSCLC: novel findings on the
      road to clinical use?
AB  - Prognostication of non-small cell lung cancer is principally based on stage, age
      and performance status. This review provides an overview of 342 potential
      prognostic biomarkers in non-small cell lung cancer described between January
      2008 and June 2013, evaluating the association between immunohistochemical
      protein expression and survival endpoint. Numerous studies proposed prognostic
      biomarkers, but many were only evaluated in a single patient cohort, and a large
      number of biomarkers revealed inconclusive findings when analyzed in more than
      one study. Only 26 proteins first described after 2008 (ALDH1A1, ANXA1, BCAR1,
      CLDN1, EIF4E, EZH2, FOLR1, FOXM1, IL7R, IL12RB2, KIAA1524, CRMP1, LOX, MCM7,
      MTA1, MTDH, NCOA3, NDRG2, NEDD9, NES, PBK, PPM1D, SIRT1, SLC7A5, SQSTM1 and WNT1)
      demonstrated a consistent prognostic association in two or more independent
      patient cohorts, thus qualifying as promising candidates for diagnostic use.
      Raised quality standards for study design and antibody validation, and
      integration of preclinical findings with clinical needs are clearly warranted.

PMID- 25599125
TI  - Polymeric nanoparticles encapsulating white tea extract for nutraceutical
      application.
AB  - With the aim to obtain controlled release and to preserve the antioxidant
      activity of the polyphenols, nanoencapsulation of white tea extract into
      polymeric nanoparticles (NPs) based on poly(epsilon-caprolactone) (PCL) and
      alginate was successfully performed. NPs were prepared by nanoprecipitation
      method and were characterized in terms of morphology and chemical properties.
      Total polyphenols and catechins contents before and after encapsulation were
      determined. Moreover, in vitro release profiles of encapsulated polyphenols from
      NPs were investigated in simulated gastrointestinal fluids. The antioxidant
      activity and stability of encapsulated extract were further evaluated.
      Interestingly, NPs released 20% of the polyphenols in simulated gastric medium,
      and 80% after 5 h at pH 7.4, showing a good capacity to control the polyphenols
      delivery. Furthermore, DPPH(*) assay confirmed that white tea extract retained
      its antioxidant activity and NPs protected tea polyphenols from degradation, thus
      opening new perspectives for the exploitation of white tea extract-loaded NPs for
      nutraceutical applications. 

PMID- 25599127
TI  - Photoinduced Dynamics of Charge Separation: From Photosynthesis to Polymer
      Fullerene Bulk Heterojunctions.
AB  - Understanding charge separation and charge transport is crucial for improving the
      efficiency of organic solar cells. Their active media are based on organic
      molecules and polymers, serving as both light-absorbing and transport layers. The
      charge-transfer (CT) states play an important role, being intermediate for free
      carrier generation and charge recombination. Here, we use light-induced electron
      paramagnetic resonance spectroscopy to study the CT dynamics in blends of the
      polymers P3HT, PCDTBT, and PTB7 with the fullerene derivative C60-PCBM. Time
      resolved EPR measurements show strong spin-polarization patterns for all polymer
      fullerene blends, confirming predominant generation of singlet CT states and
      partial orientation ordering near the donor-acceptor interface. These
      observations allow a comparison with charge separation processes in molecular
      donor-acceptor systems and in natural and artificial photosynthetic assemblies,
      and thus the elucidation of the initial steps of sequential CT in organic
      photovoltaic materials. 

PMID- 25599128
TI  - The relationship between competencies acquired through Swiss academic sports
      science courses and the job requirements.
AB  - In view of the changes in and growing variety of sports-related occupations, it
      is highly relevant for educational institutions to know how well the educational
      contents of their sport science courses meet the professional requirements. This
      study analyses the relationship between the competencies acquired through
      academic sports science courses and the requirements of the relevant jobs in
      Switzerland. The data for this empirical analysis were drawn from a sample of n =
      1054 graduates of different academic sport science programmes at all eight Swiss
      universities. The results show that academic sport science courses primarily
      communicate sports-specific expertise and practical sports skills. On the other
      hand, most graduates consider that the acquisition of interdisciplinary
      competencies plays a comparatively minor role in sport science education, even
      though these competencies are felt to be an important requirement in a variety of
      work-related environments and challenges. 

PMID- 25599126
TI  - Untargeted metabolic profiling identifies interactions between Huntington's
      disease and neuronal manganese status.
AB  - Manganese (Mn) is an essential micronutrient for development and function of the
      nervous system. Deficiencies in Mn transport have been implicated in the
      pathogenesis of Huntington's disease (HD), an autosomal dominant
      neurodegenerative disorder characterized by loss of medium spiny neurons of the
      striatum. Brain Mn levels are highest in striatum and other basal ganglia
      structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of
      HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are
      resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn
      cellular transport is associated with compensatory metabolic responses to HD
      pathology. Here we use an untargeted metabolomics approach by performing
      ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM
      MS) on control and HD immortalized mouse striatal neurons to identify metabolic
      disruptions under three Mn exposure conditions, low (vehicle), moderate (non
      cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of
      pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control
      cells. HD striatal cells also exhibited lower abundance and impaired induction of
      isobutyryl carnitine in response to increasing Mn exposure. In addition, we
      observed induction of metabolites in the pentose shunt pathway in HD striatal
      cells after high Mn exposure. These findings provide metabolic evidence of an
      interaction between the HD genotype and biologically relevant levels of Mn in a
      striatal cell model with known HD by Mn exposure interactions. The metabolic
      phenotypes detected support existing hypotheses that changes in energetic
      processes underlie the pathobiology of both HD and Mn neurotoxicity. 

PMID- 25599129
TI  - An operando surface enhanced Raman spectroscopy (SERS) study of carbon deposition
      on SOFC anodes.
AB  - Thermally robust and chemically inert Ag@SiO2 nanoprobes are employed to provide
      the surface enhanced Raman scattering (SERS) effect for an in situ/operando study
      of the early stage of carbon deposition on nickel-based solid oxide fuel cell
      (SOFC) anodes. The enhanced sensitivity to carbon enables the detection of
      different stages of coking, offering insights into intrinsic coking tolerance of
      material surfaces. Application of a thin coating of gadolinium doped ceria (GDC)
      enhances the resistance to coking of nickel surfaces. The electrochemically
      active Ni-YSZ interface appears to be more active for hydrocarbon reforming,
      resulting in the accumulation of different hydrocarbon molecules, which can be
      readily removed upon the application of an anodic current. Operando SERS is a
      powerful tool for the mechanistic study of coking in SOFC systems. It is also
      applicable to the study of other catalytic and electrochemical processes in a
      wide range of conditions. 

PMID- 25599130
TI  - Indirect measures of arterial stiffness and cognitive performance in individuals
      without traditional vascular risk factors or disease.
AB  - IMPORTANCE: Whether cognition is influenced by arterial stiffness in the absence
      of vascular disease remains uncertain. OBJECTIVE: To test the hypotheses that
      indirect measures of arterial stiffness are important predictors of cognitive
      performance and that this relationship varies depending on the presence of
      vascular disease. DESIGN, SETTING, AND PARTICIPANTS: Participants included 2573
      noninstitutionalized US adults randomly selected from 2 cycles of the National
      Health and Nutrition Examination Survey (1999-2002). The sample was stratified by
      groups based on the presence (VASC+) vs the absence (VASC-) of vascular variables
      negatively associated with cognition to assess the effects of indirect measures
      of arterial stiffness on cognitive performance. We used logistic regression to
      obtain odds ratios (ORs) and their 95% CIs. P < .05 was considered statistically
      significant. MAIN OUTCOMES AND MEASURES: The Digit Symbol Substitution Test score
      was used as a continuous variable, and the lowest quintile was designated as an
      indicator of poorer cognitive performance. RESULTS: In the VASC+ group, poorer
      cognitive performance was more likely with increasing age (OR, 1.12 [95% CI, 1.08
      1.17]; P < .001), a sedentary lifestyle (OR, 2.99 [95% CI, 1.62-5.55]; P = .002),
      and the use of dihydropyridine calcium channel blockers (OR, 9.24 [95% CI, 1.35
      63.23]; P = .02). Poorer cognitive performance in the VASC+ group was less likely
      in women (OR, 0.37 [95% CI, 0.18-0.72]; P = .02), non-Hispanic white individuals
      (OR, 0.16 [95% CI, 0.09-0.26]; P < .001), those with higher educational
      attainment (OR, 0.23 [95% CI, 0.14-0.38]; P < .001), those with higher income
      levels (OR, 0.56 [95% CI, 0.72-0.76]; P < .001), and those who used renin
      angiotensin system blockers (OR, 0.24 [95% CI, 0.07-0.79]; P = .02). In the VASC-
      group, the most important significant predictors of poorer cognitive performance
      were an ankle brachial index greater than 1.30 (OR, 18.56 [95% CI, 2.94-117.05];
      P = .002) and increased blood pressure variability (OR, 3.49 [95% CI, 1.07
      11.35]; P = .04). Among participants in the VASC- group who had both of these
      variables, the prevalence of poorer cognitive performance was greater (beta =
      16.65; P < .001). CONCLUSIONS AND RELEVANCE: Two indirect measures of arterial
      stiffness, an ankle brachial index greater than 1.30 and increased blood pressure
      variability, are associated with poorer cognitive performance among adults 60
      years or older without clinical atherosclerotic disease. Among those with
      vascular disease, factors capable of influencing arterial stiffness, such as
      exercise and the use of renin-angiotensin system blockers, may be protective
      against poorer cognitive performance.

PMID- 25599131
TI  - Nursing Home as a Reservoir of Carbapenem-Resistant Acinetobacter baumannii.
AB  - Acinetobacter baumannii is an increasingly common pathogen in healthcare settings
      globally. It is frequently resistant to multiple antimicrobial agents and there
      are recent reports on strains that are pandrug resistant. The aim of the study
      was to characterize the mechanisms of carbapenem resistance of A. baumannii
      strains from a nursing home in Zagreb and to genotype the strains. Antimicrobial
      susceptibility testing was performed by the broth microdilution method according
      to the Clinical and Laboratory Standards Institute (CLSI). PCR was used to detect
      genes encoding carbapenemases of groups A, B, and D and extended-spectrum beta
      lactamases. Genotyping of the strains was performed by rep-PCR. All strains were
      found to be resistant to ceftazidime, cefotaxime, ceftriaxone, cefepime,
      piperacillin/tazobactam, imipenem, meropenem, and ciprofloxacin. All, but one
      strain, were resistant to gentamicin. PCR revealed blaOXA-23 genes in 14, blaOXA
      24 in 5, and blaVIM in 11 strains. All strains positive for blaVIM genes
      coharbored blaOXA-23 genes. The 14 strains with OXA-23 belonged to ICL II,
      whereas the 5 strains positive for blaOXA-24 belonged to ICL I. In contrast to
      hospitals where OXA-24/40-like beta-lactamases and OXA-58 were the most
      prevalent, OXA-23-like beta-lactamases are the dominant group in the nursing
      home. OXA-58-like beta-lactamase, which is the most widespread group, was not
      found. Acquisition of blaMBL genes in A. baumannii strains was observed. Rep-PCR
      identified two clones. Two strains A10 and A13 were alocated to a novel sequence
      type ST 637. Nursing homes can act as a source of dissemination of blaOXA and
      blaMBL genes in the environment and the possible influx to the hospital
      environment. 

PMID- 25599134
TI  - A convection-driven long-range linear gradient generator with dynamic control.
AB  - We developed a novel gradient generator to achieve long range and linear chemical
      gradients with a dynamic control function. The length of the gradient can be on
      the centimetre scale. The gradient profile can be tuned by changing the flow
      rates. The device can work in both high flow rate regimes with large shear stress
      and low flow rate regimes with minimum shear stress. The drug screening function
      was demonstrated by the viability test of PC-9 cancer cells. 

PMID- 25599135
TI  - Evaluation of the difference in the rate coefficients of F2 + NOx (x = 1 or 2) ->
      F + FNOx by the stereochemical arrangement using the density functional theory.
AB  - The rate coefficient of F2 + NO -> F + FNO is 2 to 5 orders of magnitude higher
      than that of F2 + NO2 -> F + FNO2 even though bond energies of FNO and FNO2 only
      differ by ~0.2 eV. To understand the cause of having different rate coefficients
      of these two reactions, the change in total energies was calculated by varying
      the stereochemical arrangement of F2 with respect to NOx (x = 1 or 2) by the
      density functional theory (DFT), using CAM-B3LYP/6-311 G+(d) in the Gaussian
      program. The permitted approaching angle between the x-axis and the plane
      consisting of O, N, F, and phi plays a key role to restrict the reaction of NO2
      and F2 compared to the reaction of NO and F2. This restriction in the reaction
      space is considered to be the main cause of different rate coefficients depending
      on the selection of x = 1 or 2 of the reaction of F2 + NOx -> F + FNOx, which was
      also confirmed by the difference in Si etch rate using the F formed by those
      reactions. 

PMID- 25599132
TI  - B cell follicle sanctuary permits persistent productive simian immunodeficiency
      virus infection in elite controllers.
AB  - Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced
      by as much as 10,000-fold in elite controllers (ECs) compared with typical
      progressors (TPs), but sufficient viral replication persists in EC tissues to
      allow viral sequence evolution and induce excess immune activation. Here we show
      that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly
      restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC
      monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear
      productive SIV infection from extrafollicular sites, but their relative exclusion
      from B cell follicles prevents their elimination of productively infected TFH
      cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re
      distribution of productive SIV infection to non-TFH cells, with restriction of
      productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B
      cell follicles constitute 'sanctuaries' for persistent SIV replication in the
      presence of potent anti-viral CD8(+) T cell responses, potentially complicating
      efforts to cure HIV infection with therapeutic vaccination or T cell
      immunotherapy. 

PMID- 25599136
TI  - Evidence of waste electrical and electronic equipment (WEEE) relevant substances
      in polymeric food-contact articles sold on the European market.
AB  - In order to confirm the possibility that recycled fractions from the waste
      electrical and electronic equipment (WEEE) stream were illegally entering the
      European market in black polymeric food-contact articles (FCAs), bromine
      quantification, brominated flame retardant (BFR) identification combined with
      WEEE-relevant elemental analysis and polymer impurity analysis were performed.
      From the 10 selected FCAs, seven samples contained a bromine level ranging from
      57 to 5975 mg kg(-)(1), which is lower than expected to achieve flame retardancy.
      The BFRs that were present were tetrabromobisphenol A (TBBPA),
      decabromodiphenylether (decaBDE), decabromodiphenylethane (DBDPE) and 1,2
      bis(2,4,6-tribromophenoxy)ethane (BTBPE). Typical elements used in electronic
      equipment and present in WEEE were detected either at trace level or at elevated
      concentrations. In all cases when bromine was detected at higher concentrations,
      concurrently antimony was also detected, which confirms the synergetic use of
      antimony in combination with BFRs. This study describes also the measurement of
      rare earth elements where combinations of cerium, dysprosium, lanthanum,
      neodymium, praseodymium and yttrium were detected in four of the seven BFR
      positive samples. Additionally, polymer purity was investigated where in all
      cases foreign polymer fractions were detected. Despite the fact that this study
      was carried out on a very small amount of samples, there is a significant
      likelihood that WEEE has been used for the production of FCAs. 

PMID- 25599137
TI  - pH-induced structural change of a multi-tryptophan protein MPT63 with
      immunoglobulin-like fold: identification of perturbed tryptophan
      residue/residues.
AB  - The structural change of M. tuberculosis MPT63, which is predominantly a beta
      sheet protein having an immunoglobulin like fold, has been investigated in the pH
      range 7.5-1.5 using various biophysical techniques along with low-temperature
      phosphorescence (LTP) spectroscopy. MPT63 contains four Tryptophan (Trp) residues
      at 26, 48, 82, and 129. Although circular dichroism, steady-state and time
      resolved fluorescence, time-resolved anisotropy, 1-aniline-8-naphthalene sulfonic
      (ANS) acid binding, and analytical ultracentrifuge depict more open largely
      unfolded structure of MPT63 at pH 1.5 and also more accessible nature of Trp
      residues to neutral quencher at pH 1.5, it is, however, not possible to assign
      the specific Trp residue/residues being perturbed. This problem has been resolved
      using LTP of MPT63, which shows optically resolved four distinct (0, 0) bands
      corresponding to four Trp residues in the pH range 7.5-3.0. LTP at pH 1.5 clearly
      reveals that the solvent-exposed Trp 82 and the almost buried Trp 129 are
      specifically affected compared with Trp 48 and Trp 26. Lys 8 and Lys 27 are
      predicted to affect Trp 129. Tyrosine residues are found to be silent even at pH
      1.5. This type of specific perturbation in a multi-Trp protein has not been
      addressed before. LTP further indicates that partially exposed Trp 48 is
      preferentially quenched by acrylamide compared with other Trp residues at both pH
      7.5 and 1.5. The solvent-exposed Trp 82 is surprisingly found to be not quenched
      by acrylamide at pH 7.5. All the results are obtained using micromolar
      concentration of protein and without using any Trp-substituted mutant. 

PMID- 25599138
TI  - Stretch reflex improves rolling stability during hopping of a decerebrate biped
      system.
AB  - When humans hop, attitude recovery can be observed in both the sagittal and
      frontal planes. While it is agreed that the brain plays an important role in leg
      placement, the role of low-level feedback (the stretch reflex) on frontal plane
      stabilization remains unclear. Seeking to better understand the contribution of
      the soleus stretch reflex to rolling stability, we performed experiments on a
      biomimetic humanoid hopping robot. Various reflex responses to touching the
      floor, ranging from no response to long muscle activations, were examined, and
      the effect of a delay upon touching the floor was also examined. We found that
      the stretch reflex brought the system closer to stable, straight hopping. The
      presence of a delay did not affect the results; both the cases with and without a
      delay outperformed the case without a reflex response. The results of this study
      highlight the importance of low-level control in locomotion for which body
      stabilization does not require higher-level signals. 

PMID- 25599133
TI  - Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute
      myeloid leukemia.
AB  - Mutant isocitrate dehydrogenase (IDH) 1 and 2 proteins alter the epigenetic
      landscape in acute myeloid leukemia (AML) cells through production of the
      oncometabolite (R)-2-hydroxyglutarate (2-HG). Here we performed a large-scale RNA
      interference (RNAi) screen to identify genes that are synthetic lethal to the
      IDH1(R132H) mutation in AML and identified the anti-apoptotic gene BCL-2. IDH1-
      and IDH2-mutant primary human AML cells were more sensitive than IDH1/2 wild-type
      cells to ABT-199, a highly specific BCL-2 inhibitor that is currently in clinical
      trials for hematologic malignancies, both ex vivo and in xenotransplant models.
      This sensitization effect was induced by (R)-2-HG-mediated inhibition of the
      activity of cytochrome c oxidase (COX) in the mitochondrial electron transport
      chain (ETC); suppression of COX activity lowered the mitochondrial threshold to
      trigger apoptosis upon BCL-2 inhibition. Our findings indicate that IDH1/2
      mutation status may identify patients that are likely to respond to pharmacologic
      BCL-2 inhibition and form the rational basis for combining agents that disrupt
      ETC activity with ABT-199 in future clinical studies. 

PMID- 25599139
TI  - [Aspiration in a specialised weaning unit--an underestimated problem].
AB  - This retrospective case series shows that 45 % of patients aspirated straight
      after removal of the tracheal cannula. The present case series includes 82
      patients with long-term mechanical ventilation (LTMV) admitted to a specialised
      weaning unit. Aspiration was proven after patients sipped water coloured with
      patent blue V. Colour was detected with a bronchoscope after passing through the
      tracheostoma and directed toward the VC. The aspiration rate in this study is in
      good agreement with other reports in the literature.We could find no significant
      statistical differences concerning age (p = 0.97), gender (47 % vs. 49), number
      of bronchoscopies (p = 0.91) and comorbidities (p = 0.326) between patients with
      and without aspiration. The duration of the stay at the ward and the duration of
      ventilation as well as the parameter Hb at the time of admission (p = 0.566),
      CO2(p = 0.288/p = 0.716), HCO3 (p = 0.915/p = 0.612) and CRP (p = 0.402/p =
      0.523) at the time of admission and discharge also showed no significant
      differences.The Kaplan Meier curves show a considerable divergence between
      patients with and without aspiration. However, the Log Rank Test (p = 0.348) and
      the univariate Cox Regression (HR 1.4, 95 % CI 0.689 - 2.849) were not
      significant. We believe that this can be attributed to the event rate, which was
      too low in our collective. This trend to a higher mortality of patients with
      aspiration might be due to weakness of the respiratory muscles when there is
      reduced coughing. Proof of aspiration in these patients is only one aspect of a
      multidimensional problem. Larger, prospective cohort studies are needed to show
      whether aspiration can serve as a prognostic marker.

PMID- 25599140
TI  - [Pulmonary hyalinizing granuloma].
AB  - Benign lesions as pulmonary hyalinizing granuloma may mimic a malign disease. A
      63-year old patient complained dyspnea and a weight loss of 30 kg. CT-thorax
      scans showed a destructive and infiltrative pulmonary process with pleural
      thickening. Histologic examination of transbronchial and transthoracic biopsies
      as well as of biopsies taken by minithoracotomy was not conclusive. Due to
      further progression the patient underwent a left-sided pleuropneumonectomy
      despite a VO2 peak of 9 ml/kg/min. Histology revealed DIP-like infiltrations, a
      histiocytic reaction and hyaline granulomas. Among less than 100 published cases
      of pulmonary hyaline granuloma a comparable rapid progression with a total
      functional loss of the affected lung is not reported. Mostly hyalinizing
      granuloma presents with infiltrations, which may mimic lung cancer, or nodular
      lesions, partly with cavitations or calcifications. The etiology is unknown, a
      persistent immunologic response to an antigenic stimulus is discussed.
      Associations with infections, lymphomas, amyloidosis or IgG4-related disease are
      reported. Some cases have features of multifocal fibrosis. In the case reported
      none of these associations could be found. The prognosis of pulmonary hyaline
      granuloma is regarded as benign. There is no effective treatment yet. Once the
      diagnosis has been established a conservative approach as well as a resection of
      nodules and a therapeutic attempt with steroids are an option. Extensive
      resections as pleuropneumonectomy are an exception.

PMID- 25599141
TI  - [Unmet need in asthma management and future treatment options].
AB  - Despite health initiatives and extensive guideline efforts for advancing the
      management of asthma, evidence from epidemiologic studies suggests, that many
      asthma patients still have uncontrolled disease. The percentage of the
      uncontrolled disease stage is highly prevalent and eventually succeeds the 50 %
      range depending on the disease severity. There is urgent need for improved care
      particularly in moderate as well as in severe asthma. Implementation of treatment
      plans, the focus on symptom control, better patient-caretaker communication and
      most importantly improvement of specific treatment options are the cornerstones
      for success. Tiotropium, the first long-term antimuscarinic compound, was
      approved for asthma treatment in 2014, new developed inhaled corticosteroids as
      well as beta2-mimetics and inhaler types will enhance the physician's
      armamentarium to treat this disease better. Agents aimed at inhibiting cytokines,
      such as mepoluzimab, daclizumab, reslizumab and others hold to various degree
      promise in the treatment of asthma. Other agents under investigation include
      phosphodiesterase type 4 inhibitors and oligonucleotides. In summary, there is
      future promise for substantial therapeutic advances in moderate and severe
      persistent asthma.

PMID- 25599142
TI  - Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis
      in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K
      Pathways.
AB  - Daucus carota L. ssp. carota (Apiacea, wild carrot, Queen Anne's lace) has been
      used in folk medicine throughout the world and recently was shown to possess
      anticancer and antioxidant activities. This study aims to determine the
      anticancer activity of the pentane fraction (F1) and the 1:1 pentane:diethyl
      ether fraction (F2) of the Daucus Carota oil extract (DCOE) against human colon
      adenocarcinoma cell lines (HT-29 and Caco-2). Treatment of cells with various
      concentrations of F1 or F2 fractions produced a dose-dependent inhibition of cell
      proliferation. Flow cytometric analysis indicated that both fractions induced sub
      G1 phase accumulation and increased apoptotic cell death. Western blot revealed
      the activation of caspase-3, PARP cleavage, and a considerable increase in Bax
      and p53 levels, and a decrease in Bcl-2 level. Treatment of HT-29 cells with
      either fraction markedly decreased the levels of both phosphorylated Erk and Akt.
      Furthermore, the combined treatment of F1 or F2 with wortmannin showed no added
      inhibition of cell survival suggesting an effect of F1 or F2 through the
      phosphatidyl inositol 3-kinase (PI3K) pathway. This study proposes that DCOE
      fractions (F1 and F2) inhibit cell proliferation by inducing cell cycle arrest
      and apoptosis in HT-29 cells through the suppression of mitogen-activated protein
      kinase (MAPK)/Erk and PI3K/Akt pathways. 

PMID- 25599143
TI  - Inhibition of interleukin-17, interleukin-23 and the TH17 cell pathway in the
      treatment of psoriatic arthritis and psoriasis.
AB  - PURPOSE OF REVIEW: In recent years, there has been an increasing understanding of
      the importance of the TH17 lineage of T cells and related cytokines, including
      interleukin (IL)17 and IL23, not only in the biology of innate host defense but
      also in the pathogenesis of inflammatory/autoimmune diseases. These diseases
      include psoriasis, psoriatic arthritis, the broader category of
      spondyloarthritides including ankylosing spondylitis and rheumatoid arthritis. It
      is postulated that in genetically predisposed individuals, external or internal
      stimuli such as microbial antigens, alterations in the intestinal microbiome,
      biomechanical stress and/or immunologic dysregulation may lead to an increased
      expression of cytokines such as IL23, which in turn stimulate the differentiation
      and activation of TH17 and other immune cells, which are a part of the innate
      immune system that trigger adaptive immune processes and chronic inflammatory
      diseases. Herein, we explore the effect of targeting this pathway
      therapeutically. RECENT FINDINGS: New drugs that are designed to inhibit steps in
      this pathway, the IL12/IL23 inhibitor, ustekinumab, the IL17A inhibitors
      secukinumab and ixekizumab, the IL17A receptor inhibitor, brodalumab, and the
      IL23 inhibitors guselkumab and tildrakizumab, have demonstrated significant
      effectiveness in treating these diseases, particularly psoriasis, psoriatic
      arthritis and ankylosing spondylitis. SUMMARY: This article reviews the relevant
      biology, efficacy and safety of new medications targeting the TH17 pathway,
      including inhibition of IL17 and IL23, particularly in psoriasis and psoriatic
      arthritis. Especially for patients who have not gained benefit from, lost
      effectiveness to or could not use antitumour necrosis factor (TNF) medications
      for safety or tolerability reasons, having effective medicines with an
      alternative mechanism of action will improve our ability to diminish disease
      activity impact on patient lives.

PMID- 25599144
TI  - Perform kicking with or without jumping: joint coordination and kinetic
      differences between Taekwondo back kicks and jumping back kicks.
AB  - We investigated joint coordination differences between Taekwondo back kicks and
      jumping back kicks, and how jumping (in performing the latter) would alter
      engaging ground reaction forces (GRF) in executing kicking. Ten skilful athletes
      volunteered to perform both kinds of kicking within the shortest time for three
      successful trials. Three high-speed cameras and two force platforms were used for
      data collection, and the trial with the shortest execution time was selected for
      analysis. Movements were divided into the rotation and attack phases. With
      comparable execution time and maximum joint linear/angular speeds, back kicks and
      jumping back kicks differ mainly in larger GRF in the latter, and in greater
      target acceleration in the former probably because the support leg prevented
      athletes' rebounding after impact. In addition, more prominent antiphase and in
      phase coordination between the shoulder segment and knee joint, and elongated
      rotation phase were found in jumping back kicks. Larger GRF values in jumping
      back kicks were generated for jump take-off rather than for a more powerful
      attack. In back kicks although the support leg remained ground contact, greatly
      decreased GRF in the attack phase suggested that the support leg mainly served as
      a rotation axis. 

PMID- 25599145
TI  - TEMPO-mediated homocoupling of aryl Grignard reagents: mechanistic studies.
AB  - The mechanism of the TEMPO mediated oxidative homo-coupling of aryl Grignard
      reagents is investigated in detail by experimental and computational studies.
      Experimental data reveal that the nitroxide-mediated homocoupling reaction of
      aryl Grignard reagents does not occur via free aryl radicals. Evidence for the
      presence of biaryl radical anions as intermediates in the coupling reaction is
      provided. It is also shown that PhMgPh under bromide free conditions in the
      presence of TEMPO does not undergo homocoupling. However, upon addition of MgBr2,
      C-C bond formation smoothly proceeds documenting the important role of the
      bromide anions in the oxidative homocoupling. DFT calculations show that an
      intramolecular electron transfer to a Mg-complexed TEMPO ligand with subsequent
      biaryl formation in a dimeric complex is viable and in agreement with
      experimental reaction conditions. 

PMID- 25599146
TI  - Bedside burr hole for intracranial pressure monitoring performed by pediatric
      intensivists in children with CNS infections in a resource-limited setting: 10
      year experience at a single center.
AB  - OBJECTIVE: Intracranial pressure monitoring can help in early identification of
      raised intracranial pressure and in setting more informed goals for treatment. We
      describe our 10-year experience of bedside burr holes performed by pediatric
      intensivists to establish intracranial pressure monitoring in children with CNS
      infections in a resource-limited setting and the technical difficulties and
      complications encountered. DESIGN: Descriptive study of prospectively recorded
      data. SETTING: PICU of a tertiary care academic institute. PATIENTS: Consecutive
      comatose patients with raised intracranial pressure who underwent intracranial
      pressure monitoring from 2004 to 2013. INTERVENTION: An intraparenchymal (1.2 mm)
      or an intraventricular transducer (3.4 mm) (Codman) was placed by a pediatric
      intensivist through a micro burr hole using a standard protocol. Technical
      difficulties during the procedure and complications were recorded. MEASUREMENTS
      AND MAIN RESULTS: Over 10 years, 265 intracranial pressure catheters were placed
      in 259 patients, mainly for acute CNS infections (n = 242, 93.4%). Median age of
      patients was 4.8 years, youngest being 6 weeks; 21 patients (8.1%) were younger
      than 1 year. Intraparenchymal transducer was used in 252 patients (97.3%). Median
      (interquartile range) duration of intracranial pressure monitoring was 96 hours
      (72-144 hr). Complications were seen in 3.5% of patients (n = 9/259); the
      incidence was 0.28 per 1,000 hours of intracranial pressure monitoring. Procedure
      related ventriculitis occurred in three of seven patients (42.8%) with
      intraventricular catheter, in contrast to none in patients with intraparenchymal
      transducer. Overall mortality was 32.8% (n = 85). On Cox-regression analysis,
      "blood component therapy" was an independent predictor of poor outcome defined as
      death or severe neurodisability (adjusted hazard ratio, 1.58; 95% CI, 1.16-2.16;
      p = 0.004). CONCLUSIONS: In a resource-limited setting, pediatric intensivists
      can safely and successfully perform burr holes at bedside for establishing
      intraparenchymal intracranial pressure monitoring in children with acute CNS
      infections. However, our data do not support placement of ventriculostomy
      catheters by pediatric intensivists in similar settings.

PMID- 25599147
TI  - Effect of administration of neuromuscular blocking agents in children with severe
      traumatic brain injury on acute complication rates and outcomes: a secondary
      analysis from a randomized, controlled trial of therapeutic hypothermia.
AB  - OBJECTIVE: To evaluate the association between neuromuscular blocking agents and
      outcome, intracranial pressure, and medical complications in children with severe
      traumatic brain injury. DESIGN: A secondary analysis of a randomized, controlled
      trial of therapeutic hypothermia. SETTING: Seventeen hospitals in the United
      States, Australia, and New Zealand. PATIENTS: Children (< 18 yr) with severe
      traumatic brain injury. INTERVENTIONS: None for this secondary analysis.
      MEASUREMENTS AND MAIN RESULTS: Children received neuromuscular blocking agent on
      the majority of days of the study (69.6%), and the modified Pediatric Intensity
      Level of Therapy scores (modified by removing neuromuscular blocking agent
      administration from the score) were increased on days when neuromuscular blocking
      agents were used (9.67 +/- 0.21 vs 5.48 +/- 0.26; p < 0.001). Children were
      stratified into groups based on exposure to neuromuscular blocking agents (group
      1 received neuromuscular blocking agents each study day; group 2 did not). Group
      1 had increased number of daily intracranial pressure readings more than 20 mm Hg
      (4.4 +/- 1.1 vs 2.4 +/- 0.5;p = 0.015) and longer ICU and hospital length of stay
      (p = 0.003 and 0.07, respectively, Kaplan-Meier). The Glasgow Outcome Score
      Extended for Pediatrics at hospital discharge and 3, 6, and 12 months after
      traumatic brain injury and medical complications observed during the acute
      hospitalization were similar between groups. CONCLUSIONS: Administration of
      neuromuscular blocking agents was ubiquitous and daily administration of
      neuromuscular blocking agents was associated with intracranial hypertension but
      not outcomes-likely indicating that increased injury severity prompted their use.
      Despite this, neuromuscular blocking agent use was not associated with
      complications. A different study design-perhaps using randomization or
      methodologies-of a larger cohort will be required to determine if neuromuscular
      blocking agent use is helpful after severe traumatic brain injury in children.

PMID- 25599150
TI  - Glutathionylspermidine in the modification of protein SH groups: the enzymology
      and its application to study protein glutathionylation.
AB  - Cysteine is very susceptible to reactive oxygen species. In response;
      posttranslational thiol modifications such as reversible disulfide bond formation
      have arisen as protective mechanisms against undesired in vivo cysteine
      oxidation. In Gram-negative bacteria a major defense mechanism against cysteine
      overoxidation is the formation of mixed protein disulfides with low molecular
      weight thiols such as glutathione and glutathionylspermidine. In this review we
      discuss some of the mechanistic aspects of glutathionylspermidine in prokaryotes
      and extend its potential use to eukaryotes in proteomics and biochemical
      applications through an example with tissue transglutaminase and its S
      glutathionylation. 

PMID- 25599149
TI  - Molecular progress in research on fruit astringency.
AB  - Astringency is one of the most important components of fruit oral sensory
      quality. Astringency mainly comes from tannins and other polyphenolic compounds
      and causes the drying, roughening and puckering of the mouth epithelia attributed
      to the interaction between tannins and salivary proteins. There is growing
      interest in the study of fruit astringency because of the healthy properties of
      astringent substances found in fruit, including antibacterial, antiviral, anti
      inflammatory, antioxidant, anticarcinogenic, antiallergenic, hepatoprotective,
      vasodilating and antithrombotic activities. This review will focus mainly on the
      relationship between tannin structure and the astringency sensation as well as
      the biosynthetic pathways of astringent substances in fruit and their regulatory
      mechanisms. 

PMID- 25599148
TI  - Therapeutic plasma exchange may improve hemodynamics and organ failure among
      children with sepsis-induced multiple organ dysfunction syndrome receiving
      extracorporeal life support.
AB  - OBJECTIVE: To determine the effect of therapeutic plasma exchange on
      hemodynamics, organ failure, and survival in children with multiple organ
      dysfunction syndrome due to sepsis requiring extracorporeal life support. DESIGN:
      A retrospective analysis. SETTING: A PICU in an academic children's hospital.
      PATIENTS: Fourteen consecutive children with sepsis and multiple organ
      dysfunction syndrome who received therapeutic plasma exchange while on
      extracorporeal life support from 2005 to 2013. INTERVENTIONS: Median of three
      cycles of therapeutic plasma exchange with median of 1.0 times the estimated
      plasma volume per exchange. MEASUREMENTS AND MAIN RESULTS: Organ Failure Index
      and Vasoactive-Inotropic Score were measured before and after therapeutic plasma
      exchange use. PICU survival in our cohort was 71.4%. Organ Failure Index
      decreased in patients following therapeutic plasma exchange (mean +/- SD: pre,
      4.1 +/- 0.7 vs post, 2.9 +/- 0.9; p = 0.0004). Patients showed improved
      Vasoactive-Inotropic Score following therapeutic plasma exchange (median [25th
      75th]: pre, 24.5 [13.0-69.8] vs post, 5.0 [1.5-7.0]; p = 0.0002). Among all
      patients, the change in Organ Failure Index was greater for early therapeutic
      plasma exchange use than late use (early, -1.7 +/- 1.2 vs late, -0.9 +/- 0.6; p =
      0.14), similar to the change in Vasoactive-Inotropic Score (early, -67.5 [28.0
      171.2] vs late, -12.0 [7.2-18.5]; p = 0.02). Among survivors, the change in Organ
      Failure Index was greater among early therapeutic plasma exchange use than late
      use (early, -2.3 +/- 1.0 vs late, -0.8 +/- 0.8; p = 0.03), as was the change in
      Vasoactive-Inotropic Score (early, -42.0 [16.0-76.3] vs late, -12.0 [5.3-29.0]; p
      = 0.17). The mean duration of extracorporeal life support after therapeutic
      plasma exchange according to timing of therapeutic plasma exchange was not
      statistically different among all patients or among survivors. CONCLUSIONS: The
      use of therapeutic plasma exchange in children on extracorporeal life support
      with sepsis-induced multiple organ dysfunction syndrome is associated with organ
      failure recovery and improved hemodynamic status. Initiating therapeutic plasma
      exchange early in the hospital course was associated with greater improvement in
      organ dysfunction and decreased requirement for vasoactive and/or inotropic
      agents.

PMID- 25599151
TI  - Seven-membered rings through metal-free rearrangement mediated by hypervalent
      iodine.
AB  - A versatile and metal-free approach for the synthesis of carbocycles and of
      heterocycles bearing seven- and eight-membered rings is described. The strategy
      is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or
      methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs).
      Reaction conditions can be easily adjusted to give ring expansion products
      bearing different functional groups. A route to medium-ring lactones was also
      developed. 

PMID- 25599152
TI  - Chemically-modified cellulose paper as a microstructured catalytic reactor.
AB  - We discuss the successful use of chemically-modified cellulose paper as a
      microstructured catalytic reactor for the production of useful chemicals. The
      chemical modification of cellulose paper was achieved using a silane-coupling
      technique. Amine-modified paper was directly used as a base catalyst for the
      Knoevenagel condensation reaction. Methacrylate-modified paper was used for the
      immobilization of lipase and then in nonaqueous transesterification processes.
      These catalytic paper materials offer high reaction efficiencies and have
      excellent practical properties. We suggest that the paper-specific interconnected
      microstructure with pulp fiber networks provides fast mixing of the reactants and
      efficient transport of the reactants to the catalytically-active sites. This
      concept is expected to be a promising route to green and sustainable chemistry. 

PMID- 25599153
TI  - Relative stability of cis- and trans-hydrindanones.
AB  - The relative stabilities of several cis- and trans-hydrindanones were compared
      using both isomerization experiments and MM2 calculations. The generally believed
      rule that cis-hydrindanones are more stable than trans-isomers is applicable, but
      is not always true. This review introduces examples, mainly from studies in our
      laboratory, to explain these facts. 

PMID- 25599154
TI  - Lipotransfer: the potential from bench to bedside: reply.

PMID- 25599155
TI  - Carpal tunnel syndrome: US strain imaging for diagnosis.
AB  - PURPOSE: To determine the feasibility of two-dimensional (2D) ultrasonographic
      (US) strain imaging for quantifying and mapping mechanical behaviors of the
      median nerve, flexor retinaculum, and flexor tendons within the carpal tunnel in
      normal and carpal tunnel syndrome (CTS) disease states during active finger
      motion. MATERIALS AND METHODS: This prospective study was approved by the
      institutional review board; all subjects gave written informed consent and had
      both of their hands examined. Ten wrists in 10 healthy volunteers (age range, 35
      51 years) and 16 wrists in 12 patients with CTS (age range, 37-55 years) were
      examined. In the patients, CTS had been confirmed on the basis of clinical
      symptoms and results of electrophysiologic studies. Raw US signals were acquired
      and were cross correlated to enable estimation of 2D incremental displacements,
      from which 2D strains were computed. The median nerve was characterized by the
      axial normal strain, while the flexor tendons and the flexor retinaculum were
      characterized by the shear strain. Temporal mean values (mean cumulative strain
      [MCS] values) and standard deviations (standard deviations of the cumulative
      strain [SDCS]) of the spatially averaged cumulative strains in each tissue region
      over the entire cycle of finger motion were compared by using an unpaired two
      tailed Student t test. RESULTS: MCS for patients with CTS and volunteers was
      similar. The SDCS for the shear strain of the flexor retinaculum was
      significantly lower (P < .001) in patients with CTS than in healthy volunteers,
      while that for the axial strain of the median nerve was higher in healthy
      volunteers than in patients with CTS (P = .0065). CONCLUSION: US strain imaging
      can be used to quantify and map tissue kinematics in the carpal tunnel and to
      differentiate abnormal from normal median nerves in the wrist.

PMID- 25599157
TI  - Diagnosis of functionally significant coronary stenosis with exercise CT
      myocardial perfusion imaging.
AB  - PURPOSE: To assess the feasibility of exercise perfusion computed tomography (CT)
      in patients suspected of having hemodynamically significant coronary stenosis.
      MATERIALS AND METHODS: This study had institutional review board approval, and
      all patients gave informed consent. Thirty-two consecutive patients (26 men [mean
      age, 63 years] and six women [mean age, 71 years]) with 55 coronary stenoses of
      at least 50% underwent coronary CT angiography (one stenosis in 13 patients, two
      stenoses in 15 patients, and three stenoses in four patients). CT myocardial
      perfusion imaging was performed within 1 minute after patients performed supine
      exercise on an ergometer secured to the CT table. The pressure-rate product was
      computed to assess level of exercise. The myocardial enhancement ratio between
      stenotic and normally perfused territories was determined for each stenosis.
      Fractional flow reserve less than 0.8, as measured during invasive coronary
      angiography, was the reference for defining significant stenoses. Receiver
      operating characteristic curves were constructed to determine the myocardial
      enhancement ratio cutoff value. RESULTS: In the per-patient analysis, a
      myocardial enhancement ratio cutoff of 0.8 performed best for identifying
      functionally significant stenosis: Sensitivity was 95% (21 of 22 patients),
      specificity was 90% (nine of 10 patients), positive predictive value was 95% (21
      of 22 patients), negative predictive value was 90% (nine of 10 patients), and
      accuracy was 94% (30 of 32 patients). Corresponding values in the per-stenosis
      analysis were 97% (29 of 30 stenoses), 96% (23 of 24 stenoses), 97% (29 of 30
      stenoses), 96% (23 of 24 stenoses), and 96% (52 of 54 stenoses), respectively.
      CONCLUSION: Exercise CT myocardial perfusion imaging is feasible and accurate for
      assessment of the functional significance of coronary stenosis.

PMID- 25599156
TI  - Prostate cancer: diagnostic performance of real-time shear-wave elastography.
AB  - PURPOSE: To prospectively evaluate the performance of real-time ultrasonographic
      (US) shear-wave elastography (SWE) in the diagnosis of peripheral zone prostate
      cancer in patients with high and/or increasing prostate-specific antigen levels
      and/or abnormal digital rectal examination results. MATERIALS AND METHODS: After
      signing an informed consent form, men referred for transrectal prostate biopsy
      were enrolled in this prospective HIPAA-compliant two-center study, which was
      conducted with institutional review board approval. Transrectal US SWE of the
      prostate was performed after a conventional transrectal US examination and
      immediately before US-guided 12-core sextant biopsy. For each sextant, the
      maximum SWE value was measured and matched to the pathologic results of that
      sextant biopsy. The diagnostic performance of SWE was assessed at both patient
      and sextant levels. The elasticity value maximizing the Youden index was used to
      derive sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV). RESULTS: The elasticity values were matched to pathologic
      results for a total of 1040 peripheral zone sextants in 184 men. One hundred
      twenty-nine positive biopsy findings (size, >=3 mm; Gleason score, >=6) were
      identified in 68 patients. The sextant-level sensitivity, specificity, PPV, NPV,
      and area under the receiver operating characteristic curve for SWE with a cutoff
      of 35 kPa for differentiating benign from malignant lesions were 96% (95%
      confidence interval [CI]: 95%, 97%), 85% (95% CI: 83%, 87%), 48% (95% CI: 46%,
      50%), 99% (95% CI: 98%, 100%), and 95% (95% CI: 93%, 97%), respectively.
      CONCLUSION: Use of a 35-kPa threshold at SWE may provide additional information
      for the detection and biopsy guidance of prostate cancer, enabling a substantial
      reduction in the number of biopsies while ensuring that few peripheral zone
      adenocarcinomas are missed.

PMID- 25599158
TI  - Clinical Research Office of the Endourological Society global registries: a
      reliable platform for robust evidence in endourology.

PMID- 25599159
TI  - Anticipatory guidance for children and adolescents with Fetal Alcohol Spectrum
      Disorder (FASD): practice points for primary health care providers.
AB  - BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that
      describes the range of effects that can occur in an individual who was prenatally
      exposed to alcohol and includes an array of complex neurodevelopmental and
      physical findings. OBJECTIVES: To give primary healthcare providers (PHCP)
      evidence-based recommendations for supporting and managing the symptoms of FASD
      after patients have received a diagnosis. MethodsPrimary health recommendations
      for the management of children and adolescents with FASD were developed based on
      expert clinical judgment and supported by evidence-based research, where
      appropriate. The format was adapted from other health supervision practice
      guidelines as developed by the American Academy of Pediatrics. Clinical practice
      "Points" for the PHCP are highlighted. A reference table of anticipatory
      recommendations by age is presented. RESULTS: In most cases, the initial
      screening and referral for diagnosis will be made by the PHCP, and they will be
      responsible for ongoing management. It is anticipated that these recommendations
      will provide the PHCP with evidence to support the longitudinal health care of
      children and adolescents with FASD and their families as they transition
      throughout all developmental stages. CONCLUSION: There is a pressing need for the
      involvement of PHCP in the active care of children and adolescents with FASD and
      their families over the lifespan. PHCP are trained in screening, prevention, and
      management of health needs, and are in the position to coordinate sub-specialty
      referrals as needed. Engaging PHCP will provide a truly integrated care system
      for individuals with FASD and their families.

PMID- 25599160
TI  - Full but impaired activation of innate immunity effectors and virus-specific T
      cells during CMV and EBV disease following cord blood transplantation.

PMID- 25599161
TI  - Influence of age on outcome after allogeneic hematopoietic cell transplantation:
      a single center study in patients aged ?60.
AB  - Reduced intensity conditioning regimens lead to an increasing use of allogeneic
      hematopoietic cell transplantation (HCT) in elderly patients. We retrospectively
      analyzed 151 patients aged ?60 receiving allogeneic HCT 2000-2012 at our center.
      Median age was 66 years. Kaplan-Meier estimated 3-year OS was 42% with a median
      follow-up of 38 months. Cumulative incidences of progression and non-relapse
      mortality after 3 years were 38 and 24%. OS was better in the group of patients
      >65 years with a Kaplan-Meier estimated OS of 50% vs 34%, P=0.060. We observed a
      significant influence of donor age (<50 years: 53% vs >50 years: 30%, P=0.017)
      and gender match (matched: 57% vs mismatched: 32%, P=0.007) on outcome. The use
      of a matched related donor was inferior compared with a matched or mismatched
      unrelated donor (19% vs 47%, P=0.015). On multivariate analysis there was an
      increased hazard ratio for a non-gender-matched HLA-matched-related donor (hazard
      ratio 3.23, 95% confidence interval 1.55-6.74, P=0.002). Age had no significant
      impact on OS (P=0.414). In conclusion, the data suggest that older age alone has
      no negative impact on the outcome of allogeneic HCT. Transplant decision should
      be tailored to disease risk and patient performance status rather than age. 

PMID- 25599162
TI  - A retrospective comparison of BU-fludarabine and BU-CY regimens in elderly
      patients or in patients with comorbidities who received unmanipulated
      haploidentical hematopoietic SCT.

PMID- 25599163
TI  - Treatment strategies in patients with AML or high-risk myelodysplastic syndrome
      relapsed after Allo-SCT.
AB  - Non-relapse mortality after Allo-SCT has significantly decreased over the last
      years. Nevertheless, relapse remains a major cause for post SCT mortality in
      patients with AML and high-risk myelodysplastic syndrome (MDS). In this
      retrospective single-center analysis, we have analyzed the treatment outcomes of
      108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these
      patients (65%) were treated with salvage therapies containing chemotherapy alone,
      allogeneic cell-based treatment or the combination of both. Thirty-eight patients
      (35%) received palliative treatment. Median OS after diagnosis of relapse was 130
      days. Compared with patients who received chemotherapy alone, response to salvage
      therapy was significantly improved in patients treated with a combination of
      chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among
      risk factors concerning pretreatment characteristics, disease status before first
      Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to
      relapse was an independent predictor of response to salvage therapy and OS. These
      data confirmed that time to relapse after transplantation is an important
      prognostic factor. Up to now, only patients eligible for treatment regimens
      containing allogeneic cell-based interventions achieved relevant response rates. 

PMID- 25599164
TI  - Safety of voriconazole and sirolimus coadministration after allogeneic
      hematopoietic SCT.
AB  - Antifungal prophylaxis with azoles is considered standard in allogeneic
      hematopoietic SCT (allo-HSCT). Although sirolimus is being used increasingly for
      the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by
      voriconazole, and concurrent administration can lead to significantly increased
      exposure to sirolimus. We identified 67 patients with hematologic malignancies
      who underwent allo-HSCT with sirolimus, tacrolimus and low-dose MTX and received
      concomitant voriconazole prophylaxis from April 2008 to June 2011. All patients
      underwent a non-myeloablative or reduced-intensity conditioned allo-HSCT.
      Patients received sirolimus and voriconazole concurrently for a median of 113
      days. The median daily dose reduction of sirolimus at the start of
      coadministration was 90%. The median serum sirolimus trough levels before and at
      steady state of coadministration were 5.8 ng/mL (range: 0-47.6) and 6.1 ng/mL
      (range: 1-14.2) (P=0.45), respectively. One patient with an average sirolimus
      level of 6 ng/mL developed sirolimus-related thrombotic microangiopathy that
      resolved after sirolimus discontinuation. No sinusoidal obstructive syndrome was
      reported. Seventeen patients (25%) prematurely discontinued voriconazole because
      of the adverse events. Only two patients (3%) presented with possible invasive
      fungal infections at day 100. We demonstrate that sirolimus and voriconazole
      coadministration with an empiric 90% sirolimus dose reduction and close
      monitoring of sirolimus trough levels is safe and well tolerated. 

PMID- 25599165
TI  - CyBorD induction therapy in clinical practice.
AB  - Cyclophosphamide, bortezomib and dexamethasone (CyBorD) is a highly active three
      drug induction regimen for untreated transplant-eligible multiple myeloma
      patients. Although CyBorD has been evaluated only in the phase 2 setting in a
      limited number of patients, its high efficacy and ease of administration have led
      to its widespread use. Given that clinical trial efficacy can overestimate real
      life effectiveness, we reviewed our institutional experience with 109 newly
      diagnosed patients who were treated with CyBorD in a non-clinical trial setting.
      After a median of four cycles, overall response rate (ORR) and very good partial
      response rate or better (?VGPR) were 95 and 66%, respectively, comparable to
      phase 2 studies of CyBorD and other three/four-drug induction regimens. All
      patients subsequently underwent successful stem cell collection and upgraded
      responses to ORR 98% and ?VGPR 79% post transplant. At a median follow-up of 19.8
      months after diagnosis, the 2-year OS probability was 95.3% (95%CI: 89-98). The
      presence of concurrent plasmacytoma at diagnosis was the only prognostic factor
      predicting poorer survival (HR=5.56; 95%CI: 0.92-33.74; P=0.03). CyBorD was well
      tolerated, with no severe peripheral neuropathy and minimal hematologic toxicity.
      Therefore, CyBorD is a convenient, well-tolerated, highly effective induction
      regimen in preparation for autologous SCT in real-life clinical practice. 

PMID- 25599166
TI  - Varicella zoster virus reactivation after autologous SCT is a frequent event and
      associated with favorable outcome in myeloma patients.
AB  - The occurrence of varicella zoster virus (VZV) reactivation is increased after
      allogeneic transplantation, whereas limited data are available for herpes zoster
      (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic
      significance of HZ and its correlation with VZV serology in 191 consecutive
      myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found
      that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and
      in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was
      assessed as high or rather high in 70% of the patients. By immune fluorescence
      and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV
      antibodies at ASCT. Lower specific antibody titers at transplantation were
      observed in patients with HZ after ASCT than in those without reactivation
      (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared
      with patients without HZ (P=0.007). Our data indicate that VZV reactivation after
      ASCT is a frequent event carrying a significant disease burden and it is
      associated with improved survival. Low levels of specific VZV antibodies at ASCT
      suggest increased vulnerability for VZV reactivation. 

PMID- 25599167
TI  - The association between donor and recipient statin use and infections after
      allogeneic hematopoietic cell transplantation.
AB  - Recent studies have reported that statin use may be associated with improved
      outcomes in patients with sepsis or respiratory viral infections. In the setting
      of allogeneic hematopoietic cell transplantation (HCT), it has been shown that
      donor and recipient statin use is associated with reduced risks of GVHD. We
      assessed in retrospective analysis whether donor or recipient statin use impacts
      infection risk after allogeneic HCT (n=1191). Although recipient statin use was
      associated with the increased incidence of Gram-negative bacteremia (adjusted
      hazard ratio (aHR) 2.22, (95% confidence interval (CI) 1.2-4.2), P=0.01) without
      affecting mortality, donor statin use was associated with an increased incidence
      of respiratory viral infections in recipients (aHR 2.84 (95% CI 1.3-6.0),
      P=0.007). The overall incidence of invasive fungal infections and CMV
      reactivation and CMV disease were not impacted by recipient or donor statin use.
      In conclusion, this study suggests that recipient or donor statin use may be
      associated with an increased incidence of some infections without adversely
      affecting mortality. 

PMID- 25599168
TI  - Hematopoietic SCT in Iranian children 1991-2012.
AB  - This study presents the pediatric hematopoietic SCT (HSCT) activity in Iran
      between 1991 and 2012. Overall, 1105 fifteen-year-old or younger patients have
      undergone HSCT (975 allogeneic and 130 autologous). Annual HSCTs have been
      increasing steadily since 2007. HLA-matched siblings and other related donors
      were the main source of HSCs, although since 2008 a national HLA registry has
      been established to fill the gap for patients lacking a related donor. Inherited
      abnormalities of RBCs (45.88%), leukemias (27.6%) and BM failure syndromes
      (11.94%) constituted the majority of HSCTs during this period. Two-year overall
      survival and disease-free survival rates for all patients were 74.2% (95%
      confidence interval (CI): 71.6-77) and 66.3% (95% CI: 63.5-69.3), respectively.
      Leading cause of death in allogeneic group was TRM (165 deaths) and relapse
      caused the majority of deaths in the autologous group (39 deaths). All HSCTs from
      the beginning have been performed exclusively with TBI-free-conditioning
      regimens, which provides unique data for comparison with activities of other
      centers. Encouraging survival rates provide a basis for future studies on the
      extensive applicability of TBI-free-conditioning regimens in pediatric HSCT. 

PMID- 25599169
TI  - Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD
      and survival but not relapse in a large retrospective cohort.
AB  - Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30)
      after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of
      disease relapse and worse OS. However, these reports included heterogeneous
      populations with different grafts and GVHD prophylaxis. Therefore, we
      retrospectively evaluated the association of ALC30 with transplant outcomes in a
      cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and
      received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD
      prophylaxis. Median follow-up was 57 months. Lower ALC30 (?400 * 10(6)/L) was
      associated with lower OS and increased nonrelapse mortality (NRM) for the whole
      cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was
      associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as
      well as for the SD and UD groups. No association was found between lower ALC30
      and relapse. Pretransplant factors associated with lower ALC30 were: unrelated
      donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell
      dose. In this large retrospective study, ALC30?400 * 10(6)/L was associated with
      worse OS, increased NRM and severe aGVHD. 

PMID- 25599171
TI  - A review of the genetic and long-term effects of G-CSF injections in healthy
      donors: a reassuring lack of evidence for the development of haematological
      malignancies.
AB  - In 2007 the WMDA responded to the publication of two manuscripts suggesting a
      causal link between G-CSF and myeloid malignancies in healthy donors by convening
      an international symposium to examine this issue. At the time, registries
      reviewed the long-term follow-up of their healthy donors, which suggested no
      excess of leukaemia in PBSC donors compared with BM donors. Although the evidence
      for an increased risk of malignancy in healthy donors was felt to be weak, it
      could not be excluded. The WMDA, therefore, issued a statement, to be included in
      all donor consent forms, stating that it was unknown whether G-CSF increased or
      decreased the risk of later developing cancer. In 2012, with 5 years of
      additional donor follow-up and the results of several genetic studies now
      available, the clinical working group of the WMDA again reviewed the data. On the
      basis of an assessment of a continuing lack of evidence for an increased risk of
      malignancy in donors receiving G-CSF, the WMDA has re-issued a more reassuring
      statement. The revised statement was circulated to all WMDA member registries in
      late 2012 to replace the existing statement in consent forms, which now
      conclusively states that, 'Studies following large numbers of unrelated donors
      have shown that the risk of developing cancer within several years after the use
      of G-CSF is not increased compared with donors not receiving G-CSF'. Herein we
      review the evidence on which this statement is based. 

PMID- 25599170
TI  - Important impact of gingival and periodontal conditions on outcomes in SCT
      recipients.

PMID- 25599172
TI  - Strategy to enhance solid-state fluorescence and aggregation-induced emission
      enhancement effect in pyrimidine boron complexes.
AB  - The synthesis and the solution/solid-state fluorescence properties of pyrimidine
      based monoboron complexes differing in terms of the substituents [either two
      fluorine atoms (BF2 complex) or two phenyl groups (BPh2 complex)] on the boron
      atom are reported herein. Unrestricted C-Ar intramolecular rotation in the non-,
      trifluoromethyl-, and cyano-substituted derivatives resulted in negligible
      fluorescence in solution. On the other hand, methoxy- and dimethylamino
      substituted analogues caused the restriction of the C-Ar intramolecular rotation
      and consequently resulted in relatively strong fluorescence in solution. The non
      , trifluoromethyl-, and cyano-substituted derivatives showed a pronounced
      aggregation-induced emission enhancement effect. Dimethylamino-substituted
      derivatives exhibited solvatochromism in the fluorescence spectra. Substitution
      with BPh2 effectively enhanced the fluorescence quantum yield compared to the
      corresponding BF2 complexes in the solid-state. 

PMID- 25599173
TI  - Orders for intravenous proton pump inhibitors after implementation of an
      electronic alert.

PMID- 25599174
TI  - A patterned ZnO nanorod array/gas sensor fabricated by mechanoelectrospinning
      assisted selective growth.
AB  - Micropatterned ZnO nanorod arrays were fabricated by the mechanoelectrospinning
      assisted direct-writing process and the hydrothermal growth process, and utilized
      as gas sensors that exhibited excellent Ohmic behavior and sensitivity response
      to oxidizing gas NO2 at low concentrations (1-100 ppm). 

PMID- 25599175
TI  - Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using
      integrase-defective lentiviral vectors.
AB  - The utility of CRISPR-Cas9 and TALENs for genome editing may be compromised by
      their off-target activity. We show that integrase-defective lentiviral vectors
      (IDLVs) can detect such off-target cleavage with a frequency as low as 1%. In the
      case of Cas9, we find frequent off-target sites with a one-base bulge or up to 13
      mismatches between the single guide RNA (sgRNA) and its genomic target, which
      refines sgRNA design. 

PMID- 25599176
TI  - Computational analysis of cell-to-cell heterogeneity in single-cell RNA
      sequencing data reveals hidden subpopulations of cells.
AB  - Recent technical developments have enabled the transcriptomes of hundreds of
      cells to be assayed in an unbiased manner, opening up the possibility that new
      subpopulations of cells can be found. However, the effects of potential
      confounding factors, such as the cell cycle, on the heterogeneity of gene
      expression and therefore on the ability to robustly identify subpopulations
      remain unclear. We present and validate a computational approach that uses latent
      variable models to account for such hidden factors. We show that our single-cell
      latent variable model (scLVM) allows the identification of otherwise undetectable
      subpopulations of cells that correspond to different stages during the
      differentiation of naive T cells into T helper 2 cells. Our approach can be used
      not only to identify cellular subpopulations but also to tease apart different
      sources of gene expression heterogeneity in single-cell transcriptomes. 

PMID- 25599177
TI  - Multifunctional fibers for simultaneous optical, electrical and chemical
      interrogation of neural circuits in vivo.
AB  - Brain function depends on simultaneous electrical, chemical and mechanical
      signaling at the cellular level. This multiplicity has confounded efforts to
      simultaneously measure or modulate these diverse signals in vivo. Here we present
      fiber probes that allow for simultaneous optical stimulation, neural recording
      and drug delivery in behaving mice with high resolution. These fibers are
      fabricated from polymers by means of a thermal drawing process that allows for
      the integration of multiple materials and interrogation modalities into neural
      probes. Mechanical, electrical, optical and microfluidic measurements revealed
      high flexibility and functionality of the probes under bending deformation. Long
      term in vivo recordings, optogenetic stimulation, drug perturbation and analysis
      of tissue response confirmed that our probes can form stable brain-machine
      interfaces for at least 2 months. We expect that our multifunctional fibers will
      permit more detailed manipulation and analysis of neural circuits deep in the
      brain of behaving animals than achievable before. 

PMID- 25599178
TI  - Integrated genome and transcriptome sequencing of the same cell.
AB  - Single-cell genomics and single-cell transcriptomics have emerged as powerful
      tools to study the biology of single cells at a genome-wide scale. However, a
      major challenge is to sequence both genomic DNA and mRNA from the same cell,
      which would allow direct comparison of genomic variation and transcriptome
      heterogeneity. We describe a quasilinear amplification strategy to quantify
      genomic DNA and mRNA from the same cell without physically separating the nucleic
      acids before amplification. We show that the efficiency of our integrated
      approach is similar to existing methods for single-cell sequencing of either
      genomic DNA or mRNA. Further, we find that genes with high cell-to-cell
      variability in transcript numbers generally have lower genomic copy numbers, and
      vice versa, suggesting that copy number variations may drive variability in gene
      expression among individual cells. Applications of our integrated sequencing
      approach could range from gaining insights into cancer evolution and
      heterogeneity to understanding the transcriptional consequences of copy number
      variations in healthy and diseased tissues. 

PMID- 25599180
TI  - [Extranodal Metastases of Renal Cell Carcinoma to the Head and Neck: A Diagnostic
      Challenge].
AB  - BACKGROUND: Single case reports about extranodal renal cell carcinoma (RCC)
      metastasis to the head and neck (HN) often implicating unusual clinical follow
      ups are well known. Subject of our investigation is to ascertain the true meaning
      of RCC for differential diagnostic of the head and neck surgion. METHODS: We
      retrospectively review the reports of 612 patients with RCC treated in a 13-years
      period in the department of urology. RESULTS: Of the 612 RCC 191 (31%) were
      metastatic, 3 female and 4 male (mean 66.8a, 56a-78a) presented with extranodal
      metastases within the HN. Extranodal locations were parotid and thyroid glands (2
      *), tongue, forehead scin, bone and paranasal sinus. Occurrence of metastases
      were observed in mean 40.8 months (5-87) after the primary. In one patient
      metastasis to the parotid gland was the only manifestation of RCC 78 month
      treated before, the others presented with further metastases to infraclavicular
      organs. DISCUSSION: According to our results extranodal metastases of RCC to the
      HN are uncommon (1.1%). Therefore and because of the unusual location extranodal
      metastases of RCC remain a diagnostic challenge for the ENT specialist and the
      pathologist with peculiar knowledge of the oncological history of the patient
      remaining an essential condition. We found exclusive metastasis to the HN in only
      one of 7 cases. Nevertheless surgical treatment has to be considered in curative
      and symptomatic treatment strategies.

PMID- 25599181
TI  - Food immune reactivities.

PMID- 25599179
TI  - Optimizing pyramided transgenic Bt crops for sustainable pest management.
AB  - Transgenic crop pyramids producing two or more Bacillus thuringiensis (Bt) toxins
      that kill the same insect pest have been widely used to delay evolution of pest
      resistance. To assess the potential of pyramids to achieve this goal, we analyze
      data from 38 studies that report effects of ten Bt toxins used in transgenic
      crops against 15 insect pests. We find that compared with optimal low levels of
      insect survival, survival on currently used pyramids is often higher for both
      susceptible insects and insects resistant to one of the toxins in the pyramid.
      Furthermore, we find that cross-resistance and antagonism between toxins used in
      pyramids are common, and that these problems are associated with the similarity
      of the amino acid sequences of domains II and III of the toxins, respectively.
      This analysis should assist in future pyramid design and the development of
      sustainable resistance management strategies. 

PMID- 25599182
TI  - The evolution of food immune reactivity testing: why immunoglobulin G or
      immunoglobulin A antibody for food may not be reproducible from one lab to
      another.
AB  - The gold standard for identifying food reactions is the elimination-provocation
      diet. Embarking on this long, tedious journey takes an expert practitioner and a
      completely dedicated patient, with a whole lot of patience from both. In the
      contemporary fast lane, microwave, "give me a pill" popping, I-want-satisfaction
      now society, many clinicians have turned to laboratory assessments for quick
      answers to food reactivity. From the introduction of cytotoxic testing for food
      allergies in 1947 until today, food reactivity testing has evolved and branched;
      it has been both pseudoimproved and scientifically improved. With multiple
      available options for methodology, specimen types, and clinical lab, how is a
      clinician expected to find the one that fits the requirements of a particular
      practice? How, indeed, when one self-promoting paper supports a particular
      methodology, while another criticizes it? In this article, with the benefit of
      his years of training and experience as a research scientist and test development
      expert, the author, who is trained in both microbiology and immunology, discusses
      the history of food testing, analyzes the criticisms of it, reviews the
      scientific literature, and tours the methodologies. 

PMID- 25599183
TI  - Oral tolerance and its relationship to food immunoreactivities.
AB  - A child is born with almost no protective immune system other than passive
      immunity and maternal transfer of immunoglobulin G (IgG) against various food
      antigens and infectious agents. This lack provides a window of opportunity for
      infectious attacks in the first 6 mo of life as the infant's body begins to
      develop its own immune system. As the maternal IgG is catabolized, the child's
      mucosal immune system evolves its own immunocytes and starts producing a
      significant amount of immunoglobulin A (IgA) and immunoglobulin M (IgM) against
      pathogens and food antigens. This antibody production helps modulate or inhibit
      colonization by bacteria or yeast and to prevent penetration of the mucosal
      tissue by a variety of dangerous lumenal antigens. Simultaneously, the body
      develops its own suppressive mechanism or oral tolerance to avoid local and
      peripheral immune reactivities to microbial and dietary antigens. In this
      article, the author describes the (1) importance of oral tolerance in maintaining
      homeostasis against bacterial toxins and food antigens; (2) way in which antigen
      presenting cells (APCs), through their collaboration with effector T (TEFF)
      cells, T-helper (TH) cells, and regulatory T (TREG) cells, regulate the immune
      system to induce anergy or immune suppression; (3) the importance of various
      factors in the induction of oral tolerance and the consequences of its breakdown;
      and (4) the reasons why a disruption of oral tolerance to food antigens and
      bacterial toxins can result in autoimmunity. 

PMID- 25599184
TI  - Molecular mimicry as a mechanism for food immune reactivities and autoimmunity.
AB  - The mucosal immune system is constantly exposed to challenges from the antigenic
      substances found in food and released from the body's own microbial flora. The
      body's normal tolerance to friendly antigenic substances can be disrupted by a
      number of factors, such as disease, injury, shock, trauma, surgery, drugs, blood
      transfusion, environmental triggers, etc. When this disruption happens, the
      ingestion of foods containing antigenic substances that have compositions similar
      to those of the body's autoantigens can result in the production of antibodies
      that react not only against the food antigens but also the body's own tissues.
      This response is known as food autoimmune reactivity. Between 7% and 10% of the
      world's population suffers from some form of autoimmune disease. Each patient's
      antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva
      and immunoglobulin G (IgG) and IgA in the blood must be examined to give a
      complete picture of food immune reactivity. A host of health problems and
      autoimmune disorders have increasingly become associated with some of the most
      commonly consumed foods in the world, such as wheat and milk. Many of these
      problems can be traced to molecular mimicry. The peptide sequences of foods such
      as milk and wheat are similar to those of human molecules, such as myelin
      oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4
      (AQP4). This similarity can result in cross-reactivity that leads to food
      autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS),
      celiac disease (CD), and neuromyelitis optica. Further research is needed to
      determine what other foods have dangerous sequence similarities to human tissues
      and what methods are available to test for the autoantibodies resulting from
      these molecular, mimicry-induced misfires of the immune system. The
      identification and removal of corresponding food triggers can then be used as the
      basis of therapy. 

PMID- 25599185
TI  - Lectins, agglutinins, and their roles in autoimmune reactivities.
AB  - Lectins are carbohydrate-binding proteins present throughout nature that act as
      agglutinins. Approximately 30% of our food contains lectins, some of which may be
      resistant enough to digestion to enter the circulation. Because of their binding
      properties, lectins can cause nutrient deficiencies, disrupt digestion, and cause
      severe intestinal damage when consumed in excess by an individual with
      dysfunctional enzymes. These effects are followed by disruption of intestinal
      barrier integrity, which is the gateway to various autoimmunities. Shared amino
      acid motifs between dietary lectins, exogenous peptides, and various body tissues
      may lead to cross-reactivity, resulting in the production of antibodies against
      lectin and bacterial antigens, followed by autoimmunity. The detection of
      immunoglobulin G (IgG) or immunoglobulin A (IgA) antibodies against specific
      lectins may serve as a guide for the elimination of these lectins from the diet.
      It is proposed that this process can reduce the peripheral antigenic stimulus
      and, thereby, result in a diminution of disease symptoms in some-but not all
      patients with autoimmune disorders. 

PMID- 25599186
TI  - Immune reactivity to food coloring.
AB  - Artificial food dyes are made from petroleum and have been approved by the US
      Food and Drug Administration (FDA) for the enhancement of the color of processed
      foods. They are widely used in the food and pharmaceutical industries to increase
      the appeal and acceptability of their products. Synthetic food colorants can
      achieve hues not possible for natural colorants and are cheaper, more easily
      available, and last longer. However, since the use of artificial food coloring
      has become widespread, many allergic and other immune reactive disorders have
      increasingly been reported. During the past 50 y, the amount of synthetic dye
      used in foods has increased by 500%. Simultaneously, an alarming rise has
      occurred in behavioral problems in children, such as aggression, attention
      deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The
      ingestion of food delivers the greatest foreign antigenic load that challenges
      the immune system. Artificial colors can also be absorbed via the skin through
      cosmetic and pharmaceutical products. The molecules of synthetic colorants are
      small, and the immune system finds it difficult to defend the body against them.
      They can also bond to food or body proteins and, thus, are able to act in stealth
      mode to circumvent and disrupt the immune system. The consumption of synthetic
      food colors, and their ability to bind with body proteins, can have significant
      immunological consequences. This consumption can activate the inflammatory
      cascade, can result in the induction of intestinal permeability to large
      antigenic molecules, and could lead to cross-reactivities, autoimmunities, and
      even neurobehavioral disorders. The Centers for Disease Control (CDC) recently
      found a 41% increase in diagnoses of ADHD in boys of high-school age during the
      past decade. More shocking is the legal amount of artificial colorants allowed by
      the FDA in the foods, drugs, and cosmetics that we consume and use every day. The
      consuming public is largely unaware of the perilous truth behind the deceptive
      allure of artificial color. 

PMID- 25599187
TI  - Immune reactivities against gums.
AB  - CONTEXT: Different kinds of gums from various sources enjoy an extremely broad
      range of commercial and industrial use, from food and pharmaceuticals to printing
      and adhesives. Although generally recognized as safe by the US Food and Drug
      Administration (FDA), gums have a history of association with sensitive or
      allergic reactions. In addition, studies have shown that gums have a structural,
      molecular similarity to a number of common foods. A possibility exists for cross
      reactivity. OBJECTIVE: Due to the widespread use of gums in almost every aspect
      of modern life, the overall goal of the current investigation was to determine
      the degree of immune reactivity to various gum antigens in the sera of
      individuals representing the general population. DESIGN: The study was a
      randomized, controlled trial. PARTICIPANTS: 288 sera purchased from a commercial
      source. OUTCOME MEASURES: The sera was screened for immunoglobulin G (IgG) and
      immunoglobulin E (IgE) antibodies against extracts of mastic gum, carrageenan,
      xantham gum, guar gum, gum tragacanth, locust bean gum, and beta-glucan, using
      indirect enzyme-linked immunosorbent assay (ELISA) testing. For each gum antigen,
      inhibition testing was performed on the 4 sera that showed the highest IgG and
      IgE immune reactivity against the different gums used in the study. Inhibition
      testing on these same sera for sesame albumin, lentil, corn, rice, pineapple,
      peanut, pea protein, shrimp, or kidney bean was used to determine the cross
      reactivity of these foods with the gum. RESULTS: Of the 288 samples, 4.2%-27% of
      the specimens showed a significant elevation in IgG antibodies against various
      gums. Only 4 of 288, or 1.4%, showed a simultaneous elevation of the IgG antibody
      against all 7 gum extracts. For the IgE antibody, 15.6%-29.1% of the specimens
      showed an elevation against the various gums. A significant percentage of the
      specimens, 12.8%, simultaneously produced IgE antibodies against all 7 tested
      extracts. CONCLUSIONS: Overall, the percentage of elevation in IgE antibodies
      against different gum extracts, with the exception of carrageenan, was much
      higher than for the IgG antibody. The results of the current study showed that a
      subgroup of healthy individuals who produced not only IgG but also IgE antibodies
      against various gums may suffer from hidden food immune reactivities and
      sensitivities. Further study is needed to examine the clinical importance of gums
      and cross-reactive food antibodies in symptomatic individuals.

PMID- 25599188
TI  - Immune reactivities to peanut proteins, agglutinins, and oleosins.
AB  - CONTEXT: Certain individuals are sensitive enough to react to peanuts and peanut
      oil, sometimes with deadly effect. It is thus crucial to have an accurate testing
      methodology for the assessment of allergies and immune reactivities to peanuts
      and their components, such as agglutinins and oleosins. Currently, skin-prick
      testing is performed only with the water-soluble components of peanut proteins
      and can produce false negatives. Testing with all possible food antigens and with
      both immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies may offer a
      more accurate alternative. OBJECTIVE: The research team intended to measure IgG
      and IgE antibodies against peanut proteins, agglutinins, and oleosins to identify
      variations in IgG and IgE immune reactivities to these antigens among the general
      population. DESIGN: Sera from 288 healthy individuals-144 males of different
      ethnicities, aged 18-65 y with a median age of 35.5 y, and 144 females of
      different ethnicities, aged 18-65 y with a median age of 36.2 y-were obtained
      from Innovative Research, Inc. Four sera from patients with a known allergy to
      peanuts and 4 sera from individuals with no known allergy to peanuts were used as
      positive and negative controls. Several wells in the microtiter plate were coated
      with unrelated proteins, such as human serum albumin, rabbit serum albumin, and
      bovine serum albumin and used only for the determination of any background in the
      enzyme-linked immunosorbent assay (ELISA). SETTING: Immunosciences Lab, Inc, Los
      Angeles, CA, USA. OUTCOME MEASURES: The sera were screened for peanut-specific
      IgG and IgE antibodies against water-soluble proteins of peanut, peanut
      agglutinins, and peanut oleosins, using the ELISA. Color development was measured
      at 405 nM. For demonstration of the specificity of the antibodies, inhibition
      ELISA was performed with 4 sera that had very high levels of IgG and IgE
      antibodies. RESULTS: Using mean values as the cutoff, 19%, 17%, and 22% of the
      specimens tested for IgG antibodies and 14%, 11%, and 14% of the specimens tested
      for IgE antibodies produced high levels of antibodies against peanut proteins,
      agglutinins, and oleosins, respectively. CONCLUSIONS: The study's findings
      support the proposition that IgE sensitization to foods may not necessarily
      coincide with positive prick tests to commercial extracts. Falsely negative skin
      testing or IgG, IgA, or IgE antibody testing is often linked to the nature of the
      preparation of the food antigens and their use in in-vivo and in-vitro testing.
      The study's results support the need to improve the quality of food extracts used
      in the diagnosis of allergies and immune reactivity to nuts and seeds. Testing
      should use all possible food antigens and measure both IgG and IgE antibodies.

PMID- 25599189
TI  - Temporal full-colour tuning through non-steady-state upconversion.
AB  - Developing light-harvesting materials with tunable emission colours has always
      been at the forefront of colour display technologies. The variation in materials
      composition, phase and structure can provide a useful tool for producing a wide
      range of emission colours, but controlling the colour gamut in a material with a
      fixed composition remains a daunting challenge. Here, we demonstrate a
      convenient, versatile approach to dynamically fine-tuning emission in the full
      colour range from a new class of core-shell upconversion nanocrystals by
      adjusting the pulse width of infrared laser beams. Our mechanistic investigations
      suggest that the unprecedented colour tunability from these nanocrystals is
      governed by a non-steady-state upconversion process. These findings provide keen
      insights into controlling energy transfer in out-of-equilibrium optical
      processes, while offering the possibility for the construction of true three
      dimensional, full-colour display systems with high spatial resolution and locally
      addressable colour gamut. 

PMID- 25599191
TI  - Macroscopic contraction of a gel induced by the integrated motion of light-driven
      molecular motors.
AB  - Making molecular machines that can be useful in the macroscopic world is a
      challenging long-term goal of nanoscience. Inspired by the protein machinery
      found in biological systems, and based on the theoretical understanding of the
      physics of motion at the nanoscale, organic chemists have developed a number of
      molecules that can produce work by contraction or rotation when triggered by
      various external chemical or physical stimuli. In particular, basic molecular
      switches that commute between at least two thermodynamic minima and more advanced
      molecular motors that behave as dissipative units working far from equilibrium
      when fuelled with external energy have been reported. However, despite recent
      progress, the ultimate challenge of coordinating individual molecular motors in a
      continuous mechanical process that can have a measurable effect at the macroscale
      has remained elusive. Here, we show that by integrating light-driven
      unidirectional molecular rotors as reticulating units in a polymer gel, it is
      possible to amplify their individual motions to achieve macroscopic contraction
      of the material. Our system uses the incoming light to operate under far-from
      equilibrium conditions, and the work produced by the motor in the photostationary
      state is used to twist the entangled polymer chains up to the collapse of the
      gel. Our design could be a starting point to integrate nanomotors in metastable
      materials to store energy and eventually to convert it. 

PMID- 25599190
TI  - Ultralow-threshold electrically injected AlGaN nanowire ultraviolet lasers on Si
      operating at low temperature.
AB  - Ultraviolet laser radiation has been adopted in a wide range of applications as
      diverse as water purification, flexible displays, data storage, sterilization,
      diagnosis and bioagent detection. Success in developing semiconductor-based,
      compact ultraviolet laser sources, however, has been extremely limited. Here, we
      report that defect-free disordered AlGaN core-shell nanowire arrays, formed
      directly on a Si substrate, can be used to achieve highly stable, electrically
      pumped lasers across the entire ultraviolet AII (UV-AII) band (~320-340 nm) at
      low temperatures. The laser threshold is in the range of tens of amps per
      centimetre squared, which is nearly three orders of magnitude lower than those of
      previously reported quantum-well lasers. This work also reports the first
      demonstration of electrically injected AlGaN-based ultraviolet lasers
      monolithically grown on a Si substrate, and offers a new avenue for achieving
      semiconductor lasers in the ultraviolet B (UV-B) (280-320 nm) and ultraviolet C
      (UV-C) (<280 nm) bands. 

PMID- 25599192
TI  - Nanostructured lasers: Electrons and holes get closer.

PMID- 25599193
TI  - Moderators of Maintained Increase in Aerobic Exercise Among Aging Men and Women
      in a 4-Year Randomized Controlled Trial: The DR's EXTRA Study.
AB  - BACKGROUND: Little is known about factors that modify the effectiveness of
      exercise interventions in increasing exercise. We aimed to identify moderators of
      the effectiveness of aerobic exercise intervention in maintaining increased
      aerobic exercise among older individuals. METHODS: The participants of a 4-year
      randomized controlled trial were a population sample of 1410 men and women aged
      57 to 78 years. The aerobic exercise group included 185 individuals and the
      control group included 169 individuals who reported low aerobic exercise at
      baseline. Maintained increase in aerobic exercise was defined as at least 60
      minute increase in moderate-to-heavy aerobic exercise per week from baseline to 2
      and 4-year assessments. RESULTS: Individuals in the aerobic exercise group were
      2.5 (95% CI 1.5 to 3.9) times more likely to maintain increased aerobic exercise
      than those in the control group. Individuals aged < 68.5 years but not older
      individuals succeeded in maintaining increased aerobic exercise in the
      intervention group (P = .02 for interaction). Individuals who were past smokers
      (P = .02 for interaction), were working (P = .05 for interaction), or had
      symptoms of depression (P = .05 for interaction) succeeded better in maintaining
      increased aerobic exercise in the intervention group than other individuals.
      CONCLUSIONS: These findings help in more precise targeting of future exercise
      interventions among older individuals.

PMID- 25599195
TI  - Addressing millennial morbidities: accentuate the positive.

PMID- 25599194
TI  - Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute
      myocardial infarction.
AB  - Ubiquitin ligase (E3) is a decisive element of the ubiquitin-proteasome system
      (UPS), which is the main pathway for intracellular protein turnover. Recently,
      circulating E3 ligases have been increasingly considered as cancer biomarkers. In
      the present study, we aimed to determine if cardiac-specific E3 ligases in
      circulation can serve as novel predictors for early diagnosis of acute myocardial
      infarction (AMI). By screening and verifying their tissue expression patterns
      with microarray and real-time PCR analysis, six of 261 E3 ligases, including
      cardiac-specific Rnf207 and cardiac- and muscle-enriched Fbxo32/atrogin-1,
      Trim54/MuRF3, Trim63/MuRF1, Kbtbd10/KLHL41, Asb11 and Asb2 in mouse heart, were
      selected for the present study. In the AMI rats, the levels of five E3 ligases
      including Rnf207, Fbxo32, Trim54, Trim63 and Kbtbd10 in the plasma were
      significantly increased compared with control animals. Especially, the plasma
      levels of Rnf207 was markedly increased at 1 h, peaked at 3 h and decreased at 6
      24 h after ligation. Further evaluation of E3 ligases in AMI patients confirmed
      that plasma Rnf207 level increased significantly compared with that in healthy
      people and patients without AMI, and showed a similar time course to that in AMI
      rats. Simultaneously, plasma level of cardiac troponin I (cTnI) was measured by
      ELISA assays. Finally, receiver operating characteristic (ROC) curve analysis
      indicated that Rnf207 showed a similar sensitivity and specificity to the classic
      biomarker troponin I for diagnosis of AMI. Increased cardiac-specific E3 ligase
      Rnf207 in plasma may be a novel and sensitive biomarkers for AMI in humans. 

PMID- 25599196
TI  - Intraoperative cerebral angiography by intravenous contrast administration with 3
      dimensional rotational fluoroscopy in patients with intracranial aneurysms: a
      feasibility study.
AB  - BACKGROUND: Intraoperative imaging of cerebral aneurysms may be desirable in
      emergency situations with large space-occupying hematomas or to visualize vessels
      after clip placement. Mobile 3-dimensional fluoroscopes are available in a number
      of neurosurgical departments and may be useful in combination with simple image
      postprocessing to depict cerebral vessels. OBJECTIVE: To assess whether
      intracranial aneurysms are detectable with appropriate image quality with
      intraoperative 3-dimensional fluoroscopy with intravenous contrast
      administration. METHODS: Eight patients were included in the study. The patients'
      heads were fixed in a radiolucent Mayfield clamp. First, a rotational fluoroscopy
      scan was performed without contrast agent. Then, a second scan with 50 mL iodine
      contrast agent was performed. The DICOM (digital imaging and communications in
      medicine) data of both scans were transferred to an Apple PowerMac workstation,
      subtracted, and reconstructed with OsiriX imaging software. The images were
      compared with preoperative angiograms. RESULTS: No adverse effects were observed
      during contrast administration. The entire procedure from fluoroscope positioning
      to the production of usable 3-dimensional images took 5 to 6 minutes with an
      image acquisition time of 2 * 24 seconds. The configuration of the aneurysm and
      the vessel anatomy were assessable. Previous coiling limited image quality in 1
      patient. CONCLUSION: This technique quickly provides images of adequate quality
      to assess the configuration of intracranial aneurysms, which may be helpful when
      immediate intraoperative information about intracranial vessel pathologies is
      required. The positioning of the fluoroscope, image acquisition, and processing
      can be completely integrated into the surgical workflow.

PMID- 25599197
TI  - Spatial topographies of unilateral subthalamic nucleus deep brain stimulation
      efficacy for ipsilateral, contralateral, midline, and total Parkinson disease
      motor symptoms.
AB  - BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation is a successful
      intervention for medically refractory Parkinson disease, although its efficacy
      depends on optimal electrode placement. Even though the predominant effect is
      observed contralaterally, modest improvements in ipsilateral and midline symptoms
      are also observed. OBJECTIVE: To elucidate the role of contact location of
      unilateral deep brain stimulation on contralateral, ipsilateral, and axial
      subscores of Parkinson disease motor symptoms. METHODS: Eighty-six patients
      receiving first deep brain stimulation STN electrode placements were identified,
      yielding 73 patients with 3-month follow-up. Total preoperative and postoperative
      Unified Parkinson Disease Rating Scale Part III scores were obtained and divided
      into contralateral, ipsilateral, and midline subscores. Contact location was
      determined on immediate postoperative magnetic resonance imaging. A 3-dimensional
      ordinary "kriging" algorithm generated spatial interpolations for total,
      ipsilateral, contralateral, and midline symptom categories. Interpolative
      reconstructions were performed in the axial planes (z = -0.5, -1.0, -1.5, -3.5, 
      4.5, -6.0) and a sagittal plane (x = 12.0). Interpolation error and significance
      were quantified by use of a cross-validation technique and quantile-quantile
      analysis. RESULTS: There was an overall reduction in Unified Parkinson Disease
      Rating Scale Part III symptoms: total = 37.0 +/- 24.11% (P < .05), ipsilateral =
      15.9 +/- 51.8%, contralateral = 56.2 +/- 26.8% (P < .05), and midline = 26.5 +/-
      34.7%. Kriging interpolation was performed and cross-validated with quantile
      quantile analysis with high correlation (R2 > 0.92) and demonstrated regions of
      efficacy for each symptom category. Contralateral symptoms demonstrated broad
      regions of efficacy across the peri-STN area. The ipsilateral and midline regions
      of efficacy were constrained and located along the dorsal STN and caudal zona
      incerta. CONCLUSION: We provide evidence for a unique functional topographic
      window in which contralateral, ipsilateral, and midline structures may achieve
      the best efficacy. Although there are overlapping regions, laterality
      demonstrates distinct topographies. Surgical optimization should target the
      intersection of optimal regions for these symptom categories.

PMID- 25599198
TI  - Tumor progression in patients receiving adjuvant whole-brain radiotherapy vs
      localized radiotherapy after surgical resection of brain metastases.
AB  - BACKGROUND: Surgery followed by adjuvant radiotherapy is a well-established
      treatment paradigm for brain metastases. OBJECTIVE: To examine the effect of
      postsurgical whole-brain radiotherapy (WBRT) or localized radiotherapy (LRT),
      including stereotactic radiosurgery and intraoperative radiotherapy, on the rate
      of recurrence both local and distal to the resection site in the treatment of
      brain metastases. METHODS: We retrospectively identified patients who underwent
      surgery for brain metastasis at the Cleveland Clinic between 2004 and 2012.
      Institutional review board-approved chart review was conducted, and patients who
      had radiation before surgery, who had nonmetastatic lesions, or who lacked
      postadjuvant imaging were excluded. RESULTS: The final analysis included 212
      patients. One hundred fifty-six patients received WBRT, 37 received stereotactic
      radiosurgery only, and 19 received intraoperative radiotherapy. One hundred forty
      six patients were deceased, of whom 60 (41%) died with no evidence of recurrence.
      Competing risks methodology was used to test the association between adjuvant
      modality and progression. Multivariable analysis revealed no significant
      difference in the rate of recurrence at the resection site (hazard ratio [HR]
      1.46, P = .26) or of unresected, radiotherapy-treated lesions (HR 1.70, P = .41)
      for LRT vs WBRT. Patients treated with LRT had an increased hazard of the
      development of new lesions (HR 2.41, P < .001) and leptomeningeal disease (HR
      2.45, P = .04). Median survival was 16.5 months and was not significantly
      different between groups. CONCLUSION: LRT as adjuvant treatment to surgical
      resection of brain metastases is associated with an increased rate of development
      of new distant metastases and leptomeningeal disease compared with WBRT, but not
      with recurrence at the resection site or of unresected lesions treated with
      radiation.

PMID- 25599199
TI  - The 3-dimensional grid: a novel approach to stereoelectroencephalography.
AB  - BACKGROUND: Successful surgical treatment of epilepsy requires accurate
      definition of areas of ictal onset and eloquent brain. Although invasive
      monitoring can help, subdural grids cannot sample sulci or subcortical tissue;
      traditional stereoelectroencephalography depth electrodes are usually placed too
      far apart to provide sufficient resolution for mapping. OBJECTIVE: To report a
      strategy of depth electrode placement in a dense array to allow precise anatomic
      localization of epileptic and eloquent cortex. METHODS: Twenty patients with
      medically intractable epilepsy either poorly localized or found to arise adjacent
      to eloquent areas underwent placement of arrays of depth electrodes into and
      around the putative area of seizure onset with the use of framed stereotaxy. Each
      array consisted of a "grid" of parallel electrodes in a rectangular pattern with
      1 cm between entry sites. In a subset of patients, a few electrodes were placed
      initially, with additional electrodes placed in a second stage. Trajectories were
      modified to avoid cortical vessels defined on magnetic resonance imaging.
      Patients were monitored for 4 to 21 days to establish the precise location of
      seizure onset. Stimulation was performed to map cortical and subcortical eloquent
      regions. Electrode locations were coregistered for frameless stereotaxy during
      subsequent resection of seizure focus. RESULTS: Two hundred fifty-four electrodes
      were implanted. Discrete regions of seizure onset and functional cortex were
      identified, which were used during resection to remove epileptogenic tissue while
      preserving eloquent areas. There were no hemorrhagic or infectious complications;
      no patient suffered permanent neurological deficit. CONCLUSION: The 3-dimensional
      intraparenchymal grid is useful for identifying the location and extent of
      epileptic and eloquent brain.

PMID- 25599202
TI  - Intracranial blood flow changes after extracranial carotid artery stenting.
AB  - BACKGROUND: Carotid artery stenting is an endovascular treatment option for
      patients with extracranial carotid stenosis. However, intracranial blood flow
      changes following stenting have not been established. OBJECTIVE: To determine the
      effects of stenting on intracranial blood flow. METHODS: Records of patients who
      underwent stenting at our institution between 2004 and 2012 and had flow rates
      obtained pre- and poststenting by the use of quantitative magnetic resonance
      angiography were retrospectively reviewed. Percentage stenosis, stenosis length,
      and minimum vessel diameter were measured from cerebral angiography images.
      RESULTS: Eighteen patients were included. Mean age was 65 years with 67%
      presenting with symptomatic stenosis. Degree of stenosis ranged from 60% to 90%.
      Internal carotid artery (ICA) mean flow improved significantly poststenting from
      174.9 +/- 83.6 mL/min to 250.7 +/- 91.2 mL/min (P = .011). Ipsilateral middle
      cerebral artery (MCA) flow, however, was not significantly altered poststenting
      (107.8 +/- 41.6 mL/min vs 114.3 +/- 36.3 mL/min; P = .28). Univariate analysis
      revealed that improved minimum vessel diameter after stenting, but not percentage
      stenosis (P = .18) or stenosis length (P = .45), is significantly associated with
      increased ICA flow (P = .02). However, improved percentage stenosis, stenosis
      length, minimum vessel diameter, and ICA flow poststenting were not significantly
      associated with increased MCA flow (P = .64, .38, .13, .37, respectively).
      CONCLUSION: ICA flow was compromised at baseline, improving 43% on average
      poststenting. Increased minimum vessel diameter was the factor most significantly
      associated with increased flow. Conversely, MCA flow was not significantly
      compromised at baseline nor altered after stenting, suggesting compensatory
      intracranial collateral supply prestenting that redistributes following ICA
      revascularization.

PMID- 25599201
TI  - Assessing bimanual performance in brain tumor resection with NeuroTouch, a
      virtual reality simulator.
AB  - BACKGROUND: Validated procedures to objectively measure neurosurgical bimanual
      psychomotor skills are unavailable. The NeuroTouch simulator provides metrics to
      determine bimanual performance, but validation is essential before implementation
      of this platform into neurosurgical training, assessment, and curriculum
      development. OBJECTIVE: To develop, evaluate, and validate neurosurgical bimanual
      performance metrics for resection of simulated brain tumors with NeuroTouch.
      METHODS: Bimanual resection of 8 simulated brain tumors with differing color,
      stiffness, and border complexity was evaluated. Metrics assessed included blood
      loss, tumor percentage resected, total simulated normal brain volume removed,
      total tip path lengths, maximum and sum of forces used by instruments, efficiency
      index, ultrasonic aspirator path length index, coordination index, and ultrasonic
      aspirator bimanual forces ratio. Six neurosurgeons and 12 residents (6 senior and
      6 junior) were evaluated. RESULTS: Increasing tumor complexity impaired resident
      bimanual performance significantly more than neurosurgeons. Operating on black vs
      glioma-colored tumors resulted in significantly higher blood loss and lower tumor
      percentage, whereas altering tactile cues from hard to soft decreased resident
      tumor resection. Regardless of tumor complexity, significant differences were
      found between neurosurgeons, senior residents, and junior residents in efficiency
      index and ultrasonic aspirator path length index. Ultrasonic aspirator bimanual
      force ratio outlined significant differences between senior and junior residents,
      whereas coordination index demonstrated significant differences between junior
      residents and neurosurgeons. CONCLUSION: The NeuroTouch platform incorporating
      the simulated scenarios and metrics used differentiates novice from expert
      neurosurgical performance, demonstrating NeuroTouch face, content, and construct
      validity and the possibility of developing brain tumor resection proficiency
      performance benchmarks.

PMID- 25599200
TI  - Virtual reality cerebral aneurysm clipping simulation with real-time haptic
      feedback.
AB  - BACKGROUND: With the decrease in the number of cerebral aneurysms treated
      surgically and the increase of complexity of those treated surgically, there is a
      need for simulation-based tools to teach future neurosurgeons the operative
      techniques of aneurysm clipping. OBJECTIVE: To develop and evaluate the
      usefulness of a new haptic-based virtual reality simulator in the training of
      neurosurgical residents. METHODS: A real-time sensory haptic feedback virtual
      reality aneurysm clipping simulator was developed using the ImmersiveTouch
      platform. A prototype middle cerebral artery aneurysm simulation was created from
      a computed tomographic angiogram. Aneurysm and vessel volume deformation and
      haptic feedback are provided in a 3-dimensional immersive virtual reality
      environment. Intraoperative aneurysm rupture was also simulated. Seventeen
      neurosurgery residents from 3 residency programs tested the simulator and
      provided feedback on its usefulness and resemblance to real aneurysm clipping
      surgery. RESULTS: Residents thought that the simulation would be useful in
      preparing for real-life surgery. About two-thirds of the residents thought that
      the 3-dimensional immersive anatomic details provided a close resemblance to real
      operative anatomy and accurate guidance for deciding surgical approaches. They
      thought the simulation was useful for preoperative surgical rehearsal and
      neurosurgical training. A third of the residents thought that the technology in
      its current form provided realistic haptic feedback for aneurysm surgery.
      CONCLUSION: Neurosurgical residents thought that the novel immersive VR simulator
      is helpful in their training, especially because they do not get a chance to
      perform aneurysm clippings until late in their residency programs.

PMID- 25599205
TI  - Brainstem cavernous malformations: surgical results in 104 patients and a
      proposed grading system to predict neurological outcomes.
AB  - BACKGROUND: Once considered inoperable lesions in inviolable territory, brainstem
      cavernous malformations (BSCM) are now surgically curable with acceptable
      operative morbidity. Recommending surgery is a difficult decision that would be
      facilitated by a grading system designed specifically for BSCMs that predicted
      surgical outcomes. OBJECTIVE: Informed by our efforts to develop a supplementary
      grading system for arteriovenous malformations, we hypothesized that a similar
      system might predict long-term outcomes and guide clinical decision-making.
      METHODS: A consecutive, single-surgeon series of 104 patients was used to assess
      preoperative clinical and imaging predictors of microsurgical outcomes.
      Univariable logistic regression identified predictors and a multivariable
      logistic regression model tested the association of the combined predictors with
      final modified Rankin Scale scores. A grading system assigned points for lesion
      size, location crossing the brainstem's midpoint, presence of developmental
      venous anomaly, age, and time from last hemorrhage to surgery. RESULTS: Average
      maximal diameter of BSCMs was 19.5 mm; 50% crossed the axial midpoint; 54.8% had
      developmental venous anomalies; mean age was 42.1 years; and median time from
      last hemorrhage to surgery was 60 days. One patient died (0.96%), and 15 patients
      (14.4%) experienced worsened cranial nerve or motor dysfunction, of which 10
      increased their modified Rankin Scale scores (9.6%). BSCM grades ranged from 0 to
      7 points and predicted outcomes with high accuracy (receiver operating
      characteristic = 0.86, 95% confidence interval: 0.78-0.94). CONCLUSION: Rather
      than developing a grading system for all cerebral cavernous malformations that is
      weak with BSCMs, we propose a system for the patients who need it most. The BSCM
      grading system differentiates patients who might expect favorable surgical
      outcomes and offers guidance to neurosurgeons forced to select these patients.

PMID- 25599204
TI  - Adverse events associated with deep brain stimulation for movement disorders:
      analysis of 510 consecutive cases.
AB  - BACKGROUND: Although numerous studies have focused on the efficacy of deep brain
      stimulation (DBS) for movement disorders, less is known about surgical adverse
      events, especially over longer time intervals. OBJECTIVE: Here, we analyze
      adverse events in 510 consecutive cases from a tertiary movement disorders center
      at up to 10 years postoperatively. METHODS: We conducted a retrospective review
      of adverse events from craniotomies between January 2003 and March 2013. The
      adverse events were categorized into 2 broad categories--immediate perioperative
      and time-dependent postoperative events. RESULTS: Across all targets,
      perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic
      intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware
      related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation
      related event was speech disturbance in 16 (3.1%) cases. There were no
      significant differences among surgical targets with respect to the incidence of
      these events. Time-dependent postoperative events leading to the revision of a
      given DBS electrode for any reason occurred in 4.7% +/- 1.0%, 9.3% +/- 1.4%, and
      12.4% +/- 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively.
      Staged bilateral DBS was associated with approximately twice the risk of repeat
      surgery for electrode replacement vs unilateral surgery (P = .020). CONCLUSION:
      These data provide low incidences for adverse events in a large series of DBS
      surgeries for movement disorders at up to 10 years follow-up. Accurate estimates
      of adverse events will better inform patients and caregivers about the potential
      risks and benefits of surgery and provide normative data for process improvement.

PMID- 25599203
TI  - An experimental feasibility study on robotic endonasal telesurgery.
AB  - BACKGROUND: Novel robots have recently been developed specifically for endonasal
      surgery. They can deliver several thin, tentacle-like surgical instruments
      through a single nostril. Among the many potential advantages of such a robotic
      system is the prospect of telesurgery over long distances. OBJECTIVE: To describe
      a phantom pituitary tumor removal done by a surgeon in Nashville, Tennessee,
      controlling a robot located approximately 800 km away in Chapel Hill, North
      Carolina, the first remote telesurgery experiment involving tentacle-like
      concentric tube manipulators. METHODS: A phantom pituitary tumor removal
      experiment was conducted twice, once locally and once remotely, with the robotic
      system. Robot commands and video were transmitted across the Internet. The
      latency of the system was evaluated quantitatively in both local and remote cases
      to determine the effect of the 800-km distance between the surgeon and robot.
      RESULTS: We measured a control and video latency of < 100 milliseconds in the
      remote case. Qualitatively, the surgeon was able to carry out the experiment
      easily and observed no discernable difference between the remote and local cases.
      CONCLUSION: Telesurgery over long distances is feasible with this robotic system.
      In the longer term, this may enable expert skull base surgeons to help many more
      patients by performing surgeries remotely over long distances.

PMID- 25599206
TI  - Microsurgical and endoscopic anatomy of the extended retrosigmoid inframeatal
      infratemporal approach.
AB  - BACKGROUND: Different and often complex routes are available to deal with jugular
      foramen tumors with extracranial extension. OBJECTIVE: To describe a novel
      extension of the retrosigmoid approach useful to expose the extracranial area
      abutting the posterior fossa skull base. METHODS: A navigation-guided, endoscope
      assisted retrosigmoid inframeatal approach was performed on 6 cadaveric heads in
      the semisitting position, displaying an area from the internal acoustic meatus to
      the lower cranial nerves and exposing the intrapetrous internal carotid artery.
      We then continued removing the temporal bone located between the sigmoid sinus
      and the hearing apparatus, reaching the infratemporal area just lateral to the
      jugular fossa. This drilling, which we refer to as posterolateral inframeatal
      drilling, has not previously been described. Drilling of the horizontal segment
      of the occipital squama allowed good visualization of the uppermost cervical
      internal carotid artery, internal jugular vein, and lower extracranial cranial
      nerves. RESULTS: We were able to provide excellent exposure of the inframeatal
      area and of the posterior infratemporal fossa from different operative angles,
      preserving the neurovascular structures and the labyrinth in all specimens. The
      intradural operative window on the extracranial compartment was limited by the
      venous sinuses and the hearing apparatus and presented a mean width of 8.52 mm.
      Sigmoid sinus transection led to better visualization of the lateral half of the
      jugular foramen and of the uppermost cervical internal carotid artery.
      CONCLUSION: The navigation-guided endoscope-assisted extended retrosigmoid
      inframeatal infratemporal approach provides an efficient and versatile route for
      resection of jugular foramen tumors with extracranial extension.

PMID- 25599207
TI  - Correlation among anatomic landmarks, location of subthalamic deep brain
      stimulation electrodes, stimulation parameters, and side effects during
      programming monopolar review.
AB  - BACKGROUND: Clinical benefits of deep brain stimulation can be limited by the
      presence of side effects produced by current spread to adjacent structures.
      OBJECTIVE: To identify a correlation between coordinates for each individual
      contact, neighboring structures, and pattern of side effects. METHODS:
      Coordinates of the electrodes and anatomic landmarks were obtained with a
      stereotactic surgical planning software and were correlated with stimulation
      related side effects by using univariate and multivariable analyses. RESULTS:
      Monopolar stimulation elicited capsular side effects (CSEs) in 208 of 316
      contacts (65.8%) and noncapsular side effects (NCSEs) in 223 of 316 contacts
      (70.6%). The occurrence of CSEs was correlated with contact number (P = .009) and
      with the "Z" (P = .03), whereas voltage threshold to CSEs exhibited correlation
      with the internal capsule angle (P = .035). The occurrence of NCSEs was
      correlated with contact number (P = .005), "X" (P = .03), "Y" (P = .004), and the
      distance to the red nucleus (P = .001 and P = .003). There was correlation
      between voltage threshold to NCSEs and the internal capsule angle (P = .006),
      electrode's coronal angle (P = .02), "X" (P = .001), "Y" (P < .001), "Z" (P <
      .001), and the distances to the internal capsule (P = .02) and to the red nucleus
      (P = .004 and P < .001). CONCLUSION: A better understanding how patient anatomy,
      stimulation parameters, and lead location in relation to neighboring structures
      influence the occurrence of side effects can be useful to inform targeting
      strategies.

PMID- 25599208
TI  - The contralateral transfalcine transprecuneus approach to the atrium of the
      lateral ventricle: operative technique and surgical results.
AB  - BACKGROUND: Surgical approaches to the atrium of the lateral ventricle remain a
      challenging neurosurgical issue because of the eloquent nature of the surrounding
      anatomy. OBJECTIVE: To report our operative techniques and preliminary surgical
      results with the contralateral transfalcine transprecuneus approach. METHODS: A
      retrospective data review was performed of patients undergoing a contralateral
      transfalcine transprecuneus approach for the resection of lesions in the atrium
      of the lateral ventricle. Patients were positioned in the prone position with a
      30 degrees  elevation, and a 15 degrees  rotation was used. After a contralateral
      parasagittal parieto-occipital craniotomy and falx incision, the corticotomy in
      the contralateral precuneus gyrus created a corridor to the tumor. An endoscope
      was used to assist with the surgery. RESULTS: Headache was the primary
      preoperative symptom, which improved in all patients after surgery. After
      treatment, symptoms were improved in all 3 patients with hemiparesis and in 3 of
      6 patients with preexisting visual deficits; symptoms were unchanged in the other
      3 patients with visual deficits during the 13- to 38-month follow-up. Nine
      lesions were totally removed, and 1 metastatic breast cancer lesion was
      subtotally removed; all patients had good neurological outcomes and no operative
      mortality. CONCLUSION: The contralateral transfalcine transprecuneus approach is
      appropriate for most lesions in the atrium of the lateral ventricle. It provides
      a wider surgical angle (especially for the lateral extension) and reduces the
      risk of disturbance of the optic radiation compared with the conventional
      approaches. The use of magnetic resonance venography-magnetic resonance imaging
      neuronavigation makes the procedure much easier and more accurate, and the
      neuroendoscope adds to the visualization of the microscope and can reduce
      surgical complications.

PMID- 25599209
TI  - Outcomes and prognostic factors after emergent carotid artery stenting for
      hyperacute stroke within 6 hours of symptom onset.
AB  - BACKGROUND: The optimal treatment for hyperacute stroke attributable to cervical
      internal carotid artery (C-ICA) occlusion remains controversial. OBJECTIVE: This
      study sought to evaluate clinical outcomes and prognostic factors after carotid
      artery stenting (CAS) in patients with hyperacute stroke within 6 hours of onset.
      METHODS: Forty-seven patients with hyperacute stroke attributable to
      atherosclerotic C-ICA occlusion underwent emergent CAS. Forty-two patients
      (89.4%) had tandem intracranial artery occlusion (TIO). When patients showed
      remnant M1 or proximal M2 occlusions after CAS, intracranial recanalization
      therapy was performed by using pharmacologic thrombolysis and mechanical
      thrombectomy with a Solitaire stent. Clinical and radiologic data were compared
      between patients with favorable (modified Rankin scale, 0-2) and unfavorable
      outcomes. Binary logistic regression analysis was used to find independent
      prognostic factors. RESULTS: Emergent CAS was successful in all but 1 patient.
      Seven (16.7%) of 42 patients with TIO did not need further treatment, because
      thrombolysis in cerebral ischemia >=2b was achieved immediately after CAS. Of the
      35 patients who underwent intracranial recanalization therapy for remnant TIO,
      thrombolysis in cerebral ischemia >=2b was achieved in 71.4% (25 of 35). Twenty
      six patients (55.3%) had favorable outcomes, and mortality was 6.4% at 3 months.
      Time from symptom onset to carotid recanalization was inversely and independently
      associated with a favorable outcome for all patients and for those with TIO (P <
      .05). CONCLUSION: In our patient group, emergent CAS for hyperacute stroke caused
      by atherosclerotic C-ICA occlusion seemed to be effective and safe. Time to
      carotid recanalization was inversely and independently associated with a
      favorable outcome.

PMID- 25599210
TI  - Novel device and technique for minimally invasive intracerebral hematoma
      evacuation in the same setting of a ruptured intracranial aneurysm: combined
      treatment in the neurointerventional angiography suite.
AB  - BACKGROUND: The presence of intracerebral hematoma from aneurysm rupture is an
      indication for craniotomy for clot evacuation and aneurysm clipping. Some centers
      have begun securing aneurysms with coil embolization followed by clot evacuation
      in the operating room. This approach requires transporting a patient from the
      angiography suite to the operating room, which can take valuable time and
      resources. OBJECTIVE: To report our experience with 3 cases in which a novel
      technique for minimally invasive evacuation of intracerebral hematomas after
      endovascular treatment of ruptured intracranial aneurysms was used. The Penumbra
      Apollo system can be used in the angiography suite in conjunction with
      neuroendovascular techniques to simultaneously address a symptomatic hematoma
      associated with a ruptured aneurysm. METHODS: Standard preoperative computed
      tomography angiography was performed on arrival to the emergency department. The
      patients underwent diagnostic cerebral angiography followed by balloon-assisted
      coil embolization and then remained in the neurointerventional suite for
      intracerebral hematoma evacuation with the Apollo system. RESULTS: All patients
      tolerated coil embolization and hematoma evacuation well. The combined procedures
      lasted <3 hours in both cases. Two patients were eventually discharged to acute
      rehabilitation facilities less than a month after their initial insult, and 1 has
      been cleared to return to work. The other patient was transferred to hospice
      care. CONCLUSION: The Apollo aspiration system appears to be a safe and effective
      minimally invasive option for intracerebral hematoma evacuation, particularly
      when coupled with endovascular embolization of ruptured intracranial aneurysms.
      Future work will address which patient population is most likely to benefit from
      this promising technique.

PMID- 25599211
TI  - Elastase-induced intracranial dolichoectasia model in mice.
AB  - BACKGROUND: Intracranial dolichoectasia is associated with high morbidity, and
      its pathophysiology remains poorly understood. OBJECTIVE: To develop a technique
      for the creation of a murine model of dolichoectasia. METHODS: C57/BL6 mice were
      injected with 0 milliunit (mu) (control, n = 5), 15 mu (n = 7), 25 mu (n = 10),
      35 mu (n = 10), and 55 mu (n = 6) of elastase in the cisterna magna. Fourteen
      days after injection, the vasculature of the brain was perfused with MicroFil
      polymerizing compound. Tortuosity index and the percentage increase in arterial
      diameter were calculated for the basilar artery, posterior communicating
      arteries, and the A1 segment of the anterior cerebral arteries. Tortuosity index
      >10 combined with 25% increase in diameter were used to indicate success in
      achieving dolichoectasia. RESULTS: The mortality rate was 28%, 30%, 80%, and 83%
      in the 15, 25, 35, and 55 mu groups, respectively. As the 35 and 55 mu groups
      experienced unacceptable mortality rates, they were excluded from further
      analysis. The tortuosity index and percent increase arterial diameter of the 15
      and 25 mu groups for the left anterior cerebral arteries, right anterior cerebral
      arteries, left posterior communicating arteries, right posterior communicating
      arteries, and basilar artery were significantly higher (TI >10 and arterial
      diameter >25%) than in the control. There was no significant difference in
      tortuosity index or artery diameter between the 15 and 25 mu groups for any of
      the 5 artery segments. CONCLUSION: Elastase injection through the cisterna magna
      can induce intracranial dolichoectasia in mice. Fifteen to 25 mu of elastase is
      an appropriate dose to use with acceptable mortality.

PMID- 25599212
TI  - Preservation of the greater occipital nerve during suboccipital craniectomy
      results in a paradoxical increase in postoperative headaches.
AB  - BACKGROUND: Injury to the greater occipital nerve (GON) during
      suboccipital/retrosigmoid craniectomy (SOC) has been postulated as an etiology of
      postoperative headaches (HAs). We hypothesized that severe postoperative HAs may
      be due to the division of the GON during dissection. OBJECTIVE: To determine
      whether the GON plays an important role in the development of postoperative HAs.
      METHODS: A retrospective review of prospectively accrued patients undergoing SOC
      by 1 neurosurgeon at Johns Hopkins from 1995 to 2009 was performed. A total of
      280 patients were included in the study. HA was categorized into 3 groups
      according to the severity and impact on daily activities. Data were analyzed
      using a stepwise multivariate logistic regression analysis to identify
      independent factors associated with HA development. Patients with a history of
      preoperative HAs and migraine were excluded from the analysis. RESULTS: In this
      cohort, new postoperative severe HAs at last follow-up visit were found in 19% of
      patients. By multivariate analysis, only GON preservation (relative risk: 1.49;
      95% confidence interval: 1.00-2.34; P = 0.05) and wound infection (relative risk:
      2.29; 95% confidence interval: 0.91-4.25; P = 0.07) were statistically
      significant. By univariate analysis, positive dependent associations included GON
      preservation (P < .01), reconstruction of the porus with hydroxyapatite cement (P
      = 0.02), and wound infection (P < 0.01). Statistically significant differences in
      the incidence of HA after surgery were found in patients in whom the GON was
      preserved compared with patients in whom the GON was divided (P = 0.035).
      CONCLUSION: Postoperative debilitating HAs are a common complication after SOC.
      Although these HAs are probably multifactorial in nature, preservation of the GON
      during SOC is independently associated with postoperative debilitating HAs.

PMID- 25599213
TI  - Stereotactic radiosurgery for intracranial meningiomas: current concepts and
      future perspectives.
AB  - Meningiomas are among the most common adult brain tumors. Although the optimal
      management of meningiomas would provide complete elimination of the lesion, this
      cannot always be accomplished safely through resection. Therefore, other
      therapeutic modalities, such as stereotactic radiosurgery (as primary or
      adjunctive therapy), have emerged. In the current review, we have provided an
      overview of the historical outcomes of various radiosurgical modalities applied
      in the management of meningiomas. Furthermore, we provide a discussion on key
      factors (eg World Health Organization grade, lesion size, and lesion location)
      that affect tumor control and adverse event rates. We discuss recent changes in
      our understanding of meningiomas, based on molecular and genetic markers, and how
      these will change our perspective on the management of meningiomas. We conclude
      by outlining the areas in which knowledge gaps persist and provide suggestions as
      to how these can be addressed.

PMID- 25599214
TI  - Unsuccessful percutaneous endoscopic lumbar discectomy: a single-center
      experience of 10,228 cases.
AB  - BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) has remarkably
      evolved with successful results. Although PELD has gained popularity for the
      treatment of herniated disc (HD), the risk of surgical failure may be a major
      obstacle to performing PELD. We analyzed unsuccessful cases requiring
      reoperation. OBJECTIVE: To find common causes of surgical failure and elucidate
      the limitations of the conventional PELD technique. METHODS: A retrospective
      review was performed on all patients who had undergone PELD between January 2001
      and December 2012. Unsuccessful PELD was defined as a case requiring reoperation
      within 6 weeks after primary surgery. Chart review was done, and preoperative,
      intraoperative, and postoperative radiographic reviews were performed. All
      unsuccessful PELD cases were classified according to the type of HD, location of
      herniation, extruded disc migration, working channel position, and intraoperative
      and postoperative findings. RESULTS: In 12 years, 10,228 patients had undergone
      PELD; 436 (4.3%) cases were unsuccessful. The causes were incomplete removal of
      HDs in 283 patients (2.8%), recurrence in 78 (0.8%), persistent pain even after
      complete HD removal in 41 (0.4%), and approach-related pain in 21 (0.2%).
      Incomplete removal of the HD was caused by inappropriate positioning (95 cases;
      33.6%) of the working channel and occurred in central HDs (91 cases; 32.2%),
      migrated HDs (70 cases; 24.7%), and axillary type HDs (63 cases; 22.3%).
      CONCLUSION: Proper surgical indications and good working channel position are
      important for successful PELD. PELD techniques should be specifically designed to
      remove the disc fragments in various types of HD.

PMID- 25599215
TI  - Quantitative study of the opticocarotid and carotid-oculomotor windows for the
      interpeduncular fossa, before and after internal carotid artery mobilization and
      posterior communicating division.
AB  - BACKGROUND: The management of basilar apex (BX) aneurysms remains problematic.
      OBJECTIVE: We quantified the surgical exposure of the BX through the
      opticocarotid window (OCW) and the carotid-oculomotor window (COW), before and
      after mobilization of the internal carotid artery and division of the posterior
      communicating artery (PCoA). METHODS: Eleven silicone-injected cadaveric heads
      were dissected bilaterally. The surgical dissection was divided into 4 major
      steps: (1) supraorbital modified orbitozygomatic craniotomy, (2) mobilization of
      the internal carotid artery after drilling out the anterior clinoid process
      intradurally and cutting the distal dural ring, (3) drilling out the posterior
      clinoid process and dorsum sellae, and (4) dividing the PCoA from the posterior
      third portion of the vessel. A frameless navigation system was used to quantify
      the surgical exposure area of the BX through the OCW and COW. RESULTS: The total
      surgical area increased significantly from steps 1 to 4 (P < .001) in both OCW
      and COW groups. Overall, there was a larger total surgical area obtained in the
      COW compared with the OCW (P = .010). ICA mobilization increased the surgical
      area for temporary (P < .001) and permanent (P < .003) clip application in both
      windows. The division of PCoA significantly increased the overall surgical area
      for permanent clip application (P < .003). Compared with the OCW, the COW had a
      significantly increased change in the area for permanent clip application in the
      low-lying group (P = .03). CONCLUSION: When approaching the BX via the pterion
      route, the appropriate surgical step and window should be selected according to
      characteristics of the PCoA and height of the BX.

PMID- 25599216
TI  - Letter: volumetric arc therapy (RapidArc) vs Gamma Knife radiosurgery for
      multiple brain metastases.

PMID- 25599217
TI  - In reply: malignant craniopharyngioma and radiotherapy: the missing link.

PMID- 25599218
TI  - Comparison of Three Risk Scores to Predict Outcomes of Severe Lower
      Gastrointestinal Bleeding.
AB  - BACKGROUND AND AIMS: Improved medical decisions by using a score at the initial
      patient triage level may lead to improvements in patient management, outcomes,
      and resource utilization. There is no validated score for management of lower
      gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The
      aim of our study was to compare the accuracies of 3 different prognostic scores
      [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson
      index, and American Society of Anesthesiologists (ASA) score] for the prediction
      of 30-day rebleeding, surgery, and death in severe LGIB. METHODS: Data on
      consecutive patients hospitalized with severe gastrointestinal bleeding from
      January 2006 to October 2011 in our 2 tertiary academic referral centers were
      prospectively collected. Sensitivities, specificities, accuracies, and area under
      the receiver operator characteristic curve were computed for 3 scores for
      predictions of rebleeding, surgery, and mortality at 30 days. RESULTS: Two
      hundred thirty-five consecutive patients with LGIB were included between 2006 and
      2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of
      patients died. The accuracies of each score never reached 70% for predicting
      rebleeding or surgery in either. The ASA score had a highest accuracy for
      predicting mortality within 30 days (83.5%), whereas the Center for Ulcer
      Research and Education Hemostasis prognosis score and the Charlson index both had
      accuracies <75% for the prediction of death within 30 days. CONCLUSIONS: ASA
      score could be useful to predict death within 30 days. However, a new score is
      still warranted to predict all 30 days outcomes (rebleeding, surgery, and death)
      in LGIB.

PMID- 25599219
TI  - Serum Ferritin in Patients With Cirrhosis is Associated With Markers of Liver
      Insufficiency and Circulatory Dysfunction, but Not of Portal Hypertension.
AB  - BACKGROUND/AIMS: Iron overload is an increasingly recognized phenomenon in
      nonhemochromatosis cirrhosis. To evaluate the relationship between iron overload
      and liver insufficiency and portal hypertension. PATIENTS AND METHODS: Cirrhotics
      with hepatic hemodynamic and ferritin measurement (within 30 d) were included.
      Exclusion criteria were malignancy (except hepatocellular carcinoma Milan-in),
      severe chronic obstructive pulmonary disease, acute events in the previous 2
      weeks, immunosuppression, transjugular intrahepatic portosystemic shunt or portal
      vein thrombosis, and end-stage renal disease. Patients were followed-up until
      death or liver transplant. Univariate and multivariate analysis were used.
      RESULTS: Fifty-one patients were included (male 61%; median age 57 y;
      interquartile range, 47 to 66 y); Child-Pugh A 11/B 25/C 15). A positive
      correlation was observed between ferritin and markers of inflammation (C-reactive
      protein: r=0.273, P=0.06 and aspartate aminotransferase: r=0.302, P=0.035). No
      correlation between ferritin and hepatic venous pressure gradient was seen.
      Negative correlations were observed between ferritin and circulatory dysfunction
      (mean arterial pressure: r=-0.360, P=0.014 and serum sodium: r=-0.419, P=0.002).
      In contrast, associations to markers of liver failure such as international
      normalized ratio (r=0.333, P=0.005), bilirubin (r=0.378, P=0.007), albumin (r=
      0.265, P=0.082), model for end-stage liver disease (r=0.293, P=0.041), and Child
      Pugh score (r=0.392, P=0.009) were observed. No differences in survival according
      to ferritin was detected. CONCLUSIONS: In patients with cirrhosis, serum ferritin
      levels are associated with markers of liver insufficiency, inflammation, and
      circulatory dysfunction but not portal hypertension.

PMID- 25599220
TI  - Neostigmine Administered With MoviPrep Improves Bowel Preparation for Elective
      Colonoscopy in Patients With Spinal Cord Injury: A Randomized Study.
AB  - BACKGROUND: Poor preparation for elective colonoscopy is exceedingly common in
      persons with spinal cord injury (SCI). This unsatisfactory outcome is likely due
      to long-standing difficulty with evacuation and decreased colonic motility, which
      may result in inadequate responses to conventional bowel preparation regimens. We
      determined whether the addition of neostigmine to MoviPrep before elective
      colonoscopy produced a higher percentage of acceptable bowel preparations in
      patients with SCI. METHODS: Twenty-seven SCI subjects were prospectively
      randomized to 1 of 2 arms: low-volume polyethylene glycol-electrolyte lavage with
      ascorbic acid (MoviPrep) or MoviPrep plus neostigmine methylsulfate and
      glycopyrrolate (MoviPrep+NG); 28 able-bodied subjects received MoviPrep alone.
      The quality of the cleansing preparation for colonoscopy was determined by
      gastroenterologists "calibrated" to use the Ottawa Scoring System, with an
      acceptable Ottawa Score (OS) considered to be <=3. RESULTS: The administration of
      MoviPrep alone resulted in suboptimal bowel cleansing in the SCI group compared
      with the able-bodied group (50% vs. 89% of subjects had an acceptable OS;
      chi=7.94, P=0.05). However, when NG was added to MoviPrep in the SCI group, it
      markedly improved the quality of the bowel preparation, with 85% of patients then
      having an acceptable OS. The use of NG resulted in minimal bloating and
      distention before bowel evacuation (P=0.0005), and eye and muscle twitching;
      these were resolved within 1 hour after NG administration. No significant
      differences were noted among the preparation groups for adenoma detection rate
      (P=0.41). CONCLUSIONS: The combination of MoviPrep+NG was safe, well tolerated,
      and an effective approach to prepare the bowel for elective colonoscopy in
      patients with SCI. The side effects of this preparation were significant compared
      with the other treatment groups but were considered mild and anticipated.

PMID- 25599221
TI  - Visual recognition memory, manifested as long-term habituation, requires synaptic
      plasticity in V1.
AB  - Familiarity with stimuli that bring neither reward nor punishment, manifested
      through behavioral habituation, enables organisms to detect novelty and devote
      cognition to important elements of the environment. Here we describe in mice a
      form of long-term behavioral habituation to visual grating stimuli that is
      selective for stimulus orientation. Orientation-selective habituation (OSH) can
      be observed both in exploratory behavior in an open arena and in a stereotyped
      motor response to visual stimuli in head-restrained mice. We found that the
      latter behavioral response, termed a 'vidget', requires V1. Parallel
      electrophysiological recordings in V1 revealed that plasticity, in the form of
      stimulus-selective response potentiation (SRP), occurred in layer 4 of V1 as OSH
      developed. Local manipulations of V1 that prevented and reversed
      electrophysiological modifications likewise prevented and reversed memory
      demonstrated behaviorally. These findings suggest that a form of long-term visual
      recognition memory is stored via synaptic plasticity in primary sensory cortex. 

PMID- 25599222
TI  - The idiosyncratic brain: distortion of spontaneous connectivity patterns in
      autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) has been associated with a reduction in resting
      state functional connectivity, though this assertion has recently been challenged
      by reports of increased connectivity in ASD. To address these contradictory
      findings, we examined both inter- and intrahemispheric functional connectivity in
      several resting state data sets acquired from adults with high-functioning ASD
      and matched control participants. Our results reveal areas of both increased and
      decreased connectivity in multiple ASD groups as compared to control groups. We
      propose that this heterogeneity stems from a previously unrecognized ASD
      characteristic: idiosyncratic distortions of the functional connectivity pattern
      relative to the typical, canonical template. The magnitude of an individual's
      pattern distortion in homotopic interhemispheric connectivity correlated
      significantly with behavioral symptoms of ASD. We propose that individualized
      alterations in functional connectivity organization are a core characteristic of
      high-functioning ASD, and that this may account for previous discrepant findings.

PMID- 25599225
TI  - Investigations before examinations: "this is how we practice medicine here".

PMID- 25599226
TI  - Preparation of phenanthrenes from ortho-amino-biphenyls and alkynes via base
      promoted homolytic aromatic substitution.
AB  - A transition-metal-free phenanthrene synthesis starting from readily accessible
      ortho-amino-biaryls is presented. The biarylamines are in situ transformed into
      the corresponding diazonium salts which upon single electron reduction give the
      corresponding aryl radicals. Addition to an alkyne and subsequent base promoted
      homolytic aromatic substitution (BHAS) provide phenanthrenes in moderate to good
      yields. 

PMID- 25599224
TI  - The development of cortical circuits for motion discrimination.
AB  - Stimulus discrimination depends on the selectivity and variability of neural
      responses, as well as the size and correlation structure of the responsive
      population. For direction discrimination in visual cortex, only the selectivity
      of neurons has been well characterized across development. Here we show in
      ferrets that at eye opening, the cortical response to visual stimulation exhibits
      several immaturities, including a high density of active neurons that display
      prominent wave-like activity, a high degree of variability and strong noise
      correlations. Over the next three weeks, the population response becomes
      increasingly sparse, wave-like activity disappears, and variability and noise
      correlations are markedly reduced. Similar changes were observed in identified
      neuronal populations imaged repeatedly over days. Furthermore, experience with a
      moving stimulus was capable of driving a reduction in noise correlations over a
      matter of hours. These changes in variability and correlation contribute
      significantly to a marked improvement in direction discriminability over
      development. 

PMID- 25599227
TI  - Maternal holding vs oral glucose administration as nonpharmacologic analgesia in
      newborns: a functional neuroimaging study.

PMID- 25599228
TI  - Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify
      Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and
      Inflammation in Breast Adipose Tissue.
AB  - The relationship between obesity and breast cancer (BC) has focused on serum
      factors. However, the mammary gland contains adipose tissue (AT) which may enable
      the crosstalk between adipocytes and tumor cells contributing to tumor macrophage
      recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females
      and plays a major role in breast cancer development. The effects of this
      interplay on macrophage chemotaxis were examined in vitro, using co-cultures of
      mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed
      to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone
      or in combinations). In cell supernatants Luminex identified additional molecules
      with chemotactic and other pro-tumor functions. Focus on the adipokine leptin,
      which has been shown to have a central role in breast cancer pathogenesis,
      indicated it modulates macrophage phenotypes and functions. In vivo experiments
      demonstrate that mammary tumors from obese mice are larger and that bAT from
      obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic
      adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed.
      Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our
      results reveal that bAT plays a role in breast cancer development in obesity. 

PMID- 25599229
TI  - Tuning polyelectrolyte multilayer structure by exploiting natural variation in
      fucoidan chemistry.
AB  - Fucoidan is a sulfated polysaccharide that is extracted primarily from seaweed.
      The polymer contains a natural variation in chemistry based upon the species of
      seaweed from which it is extracted. We have used two different fucoidans from two
      different seaweed species (Fucus vesiculosus - FV; and Undaria pinnatifida - UP)
      as polyanions for the formation of polysaccharide-based polyelectrolyte
      multilayers (PEMs), to determine if the chemistry of different fucoidans can be
      chosen to fine-tune the structure of the polymer film. Partially acetylated
      chitosan was chosen as the polycation for the work, and the presented data
      illustrate the effect of secondary hydrogen bonding interactions on PEM build-up
      and properties. Ellipsometry and quartz crystal microbalance with dissipation
      monitoring (QCM-D) measurements performed during film build-up enabled detailed
      measurements of layer thickness, adsorbed mass, and the dynamics of the
      multilayer formation process. High quality atomic force microscopy (AFM) images
      revealed the differences in morphology of the PEMs formed from the two fucoidans,
      and allowed for a more direct layer thickness measurement. X-ray photoelectron
      spectroscopy (XPS) confirmed the chemistry of the films, and an indication of the
      altered interactions between chitosan and fucoidan with variation in fucoidan
      type, but also with layer number. Distinct differences were observed between
      multilayers formed with the two fucoidans, with those constructed using UP having
      thinner, denser, less hydrated layers than those constructed using FV. These
      differences are discussed in the context of their varied chemistry, primarily
      their difference in molecular weight and degree of acetylation. 

PMID- 25599230
TI  - Spinal cord stimulation attenuates temporal summation in patients with
      neuropathic pain.
AB  - Evidence has shown that electrical stimulation at the dorsal columns attenuated
      the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study
      was aimed to test the effect of spinal cord stimulation (SCS) on temporal
      summation (TS), the clinical correlate of the wind-up phenomenon in patients with
      radicular leg pain. Eighteen patients with SCS implants were tested both 30
      minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in
      a random order. Temporal summation was evaluated in the most painful site in the
      affected leg and in the corresponding area in the contralateral leg by applying a
      tonic painful heat stimulus (46.5 degrees C; 120 seconds) and simultaneous
      recording of the perceived heat pain intensity. Patients were also requested to
      report their clinical pain intensity (0-100 numerical pain scale) during SCS "ON"
      and "OFF". The Wilcoxon signed rank test was used in the comparisons between SCS
      "ON" and "OFF". Spinal cord stimulation activation significantly attenuated
      clinical pain intensity (from 66 +/- 18 to 27 +/- 31, P < 0.001). In the
      nonpainful leg, SCS activation failed to produce an effect on TS (24 +/- 20 vs 21
      +/- 24 in SCS "OFF" and "ON", respectively; P = 0.277). In contrast, a
      significant decrease in the magnitude of TS in the affected leg was observed in
      response to SCS activation (from 32 +/- 33 to 19 +/- 24; P = 0.017). These
      results suggest that attenuation of TS, which likely represents suppression of
      hyperexcitability in spinal cord neurons, is a possible mechanism underlying SCS
      analgesia in patients with neuropathic pain.

PMID- 25599231
TI  - Inflammatory-induced changes in synaptic drive and postsynaptic AMPARs in lamina
      II dorsal horn neurons are cell-type specific.
AB  - Persistent peripheral inflammation alters trafficking of AMPA receptors (AMPARs)
      at the synapses between primary afferents and dorsal horn (DH) neurons that
      contribute to the maintenance of inflammatory pain. However, whether peripheral
      inflammation changes the synaptic activity within the DH circuitry and how it
      modulates synaptic AMPARs in different neuronal types still remain unknown. We
      find that complete Freund adjuvant (CFA)-induced peripheral inflammation
      prominently augments excitatory neurotransmission in rat lamina II neurons
      characterized by intrinsic adapting firing properties and apparently decreases it
      in the tonic firing lamina II neurons, suggesting different roles of these types
      of interneurons in pain processing. Peripheral inflammation also differentially
      changes inhibitory neurotransmission in these neuronal types, shifting the
      balance between neuronal excitation and inhibition toward excitation of the
      adapting firing, but toward inhibition of the tonic firing lamina II neurons.
      Synaptic AMPARs were differentially changed in the adapting firing and the tonic
      firing neurons, implying different mechanisms of AMPAR adjustment at the synapses
      in these types of interneurons during persistent inflammation. The inflammatory
      induced, neuron-type specific changes in synaptic drive within the DH circuitry
      and synaptic AMPAR functioning in lamina II neurons may contribute to the
      persistent pain maintenance.

PMID- 25599232
TI  - Variations in potassium channel genes are associated with distinct trajectories
      of persistent breast pain after breast cancer surgery.
AB  - Persistent pain after breast cancer surgery is a common clinical problem. Given
      the role of potassium channels in modulating neuronal excitability, coupled with
      recently published genetic associations with preoperative breast pain, we
      hypothesized that variations in potassium channel genes will be associated with
      persistent postsurgical breast pain. In this study, associations between 10
      potassium channel genes and persistent breast pain were evaluated. Using growth
      mixture modeling (GMM), 4 distinct latent classes of patients, who were assessed
      before and monthly for 6 months after breast cancer surgery, were identified
      previously (ie, No Pain, Mild Pain, Moderate Pain, Severe Pain). Genotyping was
      done using a custom array. Using logistic regression analyses, significant
      differences in a number of genotype or haplotype frequencies were found between:
      Mild Pain vs No Pain and Severe Pain vs No Pain classes. Seven single-nucleotide
      polymorphisms (SNPs) across 5 genes (ie, potassium voltage-gated channel,
      subfamily A, member 1 [KCNA1], potassium voltage-gated channel, subfamily D,
      member 2 [KCND2], potassium inwardly rectifying channel, subfamily J, members 3
      and 6 (KCNJ3 and KCNJ6), potassium channel, subfamily K, member 9 [KCNK9]) were
      associated with membership in the Mild Pain class. In addition, 3 SNPs and 1
      haplotype across 4 genes (ie, KCND2, KCNJ3, KCNJ6, KCNK9) were associated with
      membership in the Severe Pain class. These findings suggest that variations in
      potassium channel genes are associated with both mild and severe persistent
      breast pain after breast cancer surgery. Although findings from this study
      warrant replication, they provide intriguing preliminary information on potential
      therapeutic targets.

PMID- 25599223
TI  - Psychiatric genome-wide association study analyses implicate neuronal, immune and
      histone pathways.
AB  - Genome-wide association studies (GWAS) of psychiatric disorders have identified
      multiple genetic associations with such disorders, but better methods are needed
      to derive the underlying biological mechanisms that these signals indicate. We
      sought to identify biological pathways in GWAS data from over 60,000 participants
      from the Psychiatric Genomics Consortium. We developed an analysis framework to
      rank pathways that requires only summary statistics. We combined this score
      across disorders to find common pathways across three adult psychiatric
      disorders: schizophrenia, major depression and bipolar disorder. Histone
      methylation processes showed the strongest association, and we also found
      statistically significant evidence for associations with multiple immune and
      neuronal signaling pathways and with the postsynaptic density. Our study
      indicates that risk variants for psychiatric disorders aggregate in particular
      biological pathways and that these pathways are frequently shared between
      disorders. Our results confirm known mechanisms and suggest several novel
      insights into the etiology of psychiatric disorders. 

PMID- 25599235
TI  - Distinguishing problematic from nonproblematic postsurgical pain: a pain
      trajectory analysis after total knee arthroplasty.
AB  - The goal of this study was to follow a cohort of patients undergoing total knee
      arthroplasty over time to: (1) identify and describe the various pain
      trajectories beginning preoperatively and for up to 12 months after surgery, (2)
      identify baseline predictors of trajectory group membership, and (3) identify
      trajectory groups associated with poor psychosocial outcomes 12 months after
      surgery. One hundred seventy-three participants (female = 85 [49%]; mean age
      [years] = 62.9, SD = 6.8) completed pain and psychological questionnaires and
      functional performance tests preoperatively and 4 days, 6 weeks, and 3 and 12
      months after total knee arthroplasty. Using growth mixture modeling, results
      showed that a 4-group model, with a quadratic slope and baseline pain data
      predicting trajectory group membership, best fit the data (Akaike information
      criterion = 2772.27). The first 3 pain trajectories represent various rates of
      recovery ending with relatively low levels of pain 12 months after surgery. Group
      4, the constant high pain group, comprises patients who have a neutral or
      positive pain slope and do not show improvement in their pain experience over the
      first year after surgery. This model suggests that preoperative pain levels are
      predictive of pain trajectory group membership and moderate preoperative pain, as
      opposed to low or high pain, is a risk factor for a neutral or positive pain
      trajectory postoperatively. Consistent with previous studies, these results show
      that postoperative pain is not a homogeneous condition and point to the
      importance of examining intraindividual pain fluctuations as they relate to pain
      interventions and prevention strategies.

PMID- 25599236
TI  - Do patients with chronic pain show autonomic arousal when confronted with feared
      movements? An experimental investigation of the fear-avoidance model.
AB  - The relevance of a phobia-based conceptualization of fear for individuals with
      chronic pain has been much debated in the literature. This study investigated
      whether patients with highly fearful chronic low back pain show distinct
      physiological reaction patterns compared with less fearful patients when
      anticipating aversive back pain-related movements. We used an idiosyncratic fear
      induction paradigm and collected 2 different measures of autonomic nervous system
      activation and muscle tension in the lower back. We identified 2 distinct
      psychophysiological response patterns. One pattern was characterized by a
      moderate increase in skin conductance, interbeat interval (IBI) increase, and
      muscle tension increase in the lower back. This response was interpreted as an
      attention reaction to a moderately stressful event. The other pattern, found in
      58% of the participants, was characterized by a higher skin conductance response,
      IBI decrease, and muscle tension increase in the lower back. According to Bradley
      and Lang defense cascade model, this response is typical of a fear reaction.
      Participants showing the psychophysiological pattern typical of fear also had
      elevated scores on some self-report measures of components of the fear-avoidance
      model, relative to participants showing the reaction pattern characteristic of
      attention. This study is the first to provide psychophysiological evidence for
      the fear-avoidance model of chronic pain.

PMID- 25599234
TI  - Heritability of pain catastrophizing and associations with experimental pain
      outcomes: a twin study.
AB  - This study used a twin paradigm to examine genetic and environmental
      contributions to pain catastrophizing and the observed association between pain
      catastrophizing and cold-pressor task (CPT) outcomes. Male and female monozygotic
      (n = 206) and dizygotic twins (n = 194) from the University of Washington Twin
      Registry completed a measure of pain catastrophizing and performed a CPT
      challenge. As expected, pain catastrophizing emerged as a significant predictor
      of several CPT outcomes, including cold-pressor Immersion Tolerance, Pain
      Tolerance, and Delayed Pain Rating. The heritability estimate for pain
      catastrophizing was found to be 37% with the remaining 63% of variance
      attributable to unique environmental influence. Additionally, the observed
      associations between pain catastrophizing and CPT outcomes were not found
      attributable to shared genetics or environmental exposure, which suggests a
      direct relationship between catastrophizing and experimental pain outcomes. This
      study is the first to examine the heritability of pain catastrophizing and
      potential processes by which pain catastrophizing is related to experimental pain
      response.

PMID- 25599237
TI  - A new objective method for acquisition and quantification of reflex receptive
      fields.
AB  - The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex
      correlated with pain perception. Assessment of this objective physiological
      measure constitutes the core of existing methods for quantification of reflex
      receptive fields (RRFs), which however still suffer from a certain degree of
      subjective involvement. This article proposes a strictly objective methodology
      for RRF quantification based on automated identification of NWR thresholds (NWR
      Ts). Nociceptive withdrawal reflex thresholds were determined for 10 individual
      stimulation sites using an interleaved up-down staircase method. Reflexes were
      detected from electromyography by evaluation of interval peak z scores and
      application of conduction velocity analysis. Reflex receptive field areas were
      quantified from interpolated mappings of NWR-Ts and compared with existing RRF
      quantifications. A total of 3 repeated measures were performed in 2 different
      sessions to evaluate the test-retest reliability of the various quantifications,
      using coefficients of repeatability (CRs) and hypothetical sample sizes. The
      novel quantifications based on identification of NWR-Ts showed a similar level of
      reliability within and between sessions, whereas existing quantifications all
      demonstrated worse between-session than within-session reliability. The NWR-T
      based quantifications required a smaller sample size than any of the existing RRF
      measures to detect a clinically relevant effect in a crossover study design
      involving more than 1 session. Of all measures, quantification from mapping of
      inversed NWR-Ts demonstrated superior reliability both within (CR, 0.25) and
      between sessions (CR, 0.28). The study presents a more reliable and robust
      quantification of the RRF to be used as biomarker of pain hypersensitivity in
      clinical and experimental research. 

PMID- 25599233
TI  - Oxidation-sensitive nociception involved in endometriosis-associated pain.
AB  - Endometriosis is a disease characterized by the growth of endometrial tissue
      outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid
      (PF) of women with endometriosis is a dynamic milieu and is rich in inflammatory
      markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2alpha,
      and lipid peroxides; and the endometriotic tissue is innervated with nociceptors.
      Our clinical study showed that the abundance of oxidatively modified lipoproteins
      in the PF of women with endometriosis and the ability of antioxidant
      supplementation to alleviate endometriosis-associated pain. We hypothesized that
      oxidatively modified lipoproteins present in the PF are the major source of
      nociceptive molecules that play a key role in endometriosis-associated pain. In
      this study, PF obtained from women with endometriosis or control women were used
      for (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules,
      (2) the ability of such molecules to induce nociception, and (3) the ability of
      antioxidants to suppress this nociception. LC-MS/MS showed the generation of
      eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF.
      Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular)
      in CD-1 mice and nociception in the Hargreaves paw withdrawal latency assay in
      Sprague-Dawley rats. Antioxidants, vitamin E and N-acetylcysteine, and the
      nonsteroidal anti-inflammatory drug indomethacin suppressed the pain-inducing
      ability of oxidatively modified lipoproteins. Treatment of human endometrial
      cells with oxidatively modified lipoproteins or PF from women with endometriosis
      showed upregulation of similar genes belonging to opioid and inflammatory
      pathways. Our finding that oxidatively modified lipoproteins can induce
      nociception has a broader impact not only on the treatment of endometriosis
      associated pain but also on other diseases associated with chronic pain.

PMID- 25599239
TI  - Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain
      model.
AB  - Chronic widespread pain is a serious medical problem, yet the mechanisms of
      nociception and pain are poorly understood. Using a reserpine-induced pain model
      originally reported as a putative animal model for fibromyalgia, this study was
      undertaken to examine the following: (1) expression of several ion channels
      responsible for pain, mechanotransduction, and generation/propagation of action
      potentials in the dorsal root ganglion (DRG), (2) activities of peripheral
      nociceptive afferents, and (3) alterations in spinal microglial cells. A
      significant increase in mRNA expression of the acid-sensing ion channel (ASIC)-3
      was detected in the DRG, and the behavioral mechanical hyperalgesia was
      significantly reversed by subcutaneous injection of APETx2, a selective blocker
      of ASIC3. Single-fiber recordings in vitro revealed facilitated mechanical
      responses of mechanoresponsive C-fibers both in the skin and muscle although the
      proportion of mechanoresponsive C-nociceptors was paradoxically decreased. In the
      spinal dorsal horn, microglial cells labeled with Iba1 immunoreactivity was
      activated, especially in laminae I-II where the nociceptive input is mainly
      processed compared with the other laminae. The activated microglia and behavioral
      hyperalgesia were significantly tranquilized by intraperitoneal injection of
      minocycline. These results suggest that the increase in ASIC3 in the DRG
      facilitated mechanical response of the remaining C-nociceptors and that activated
      spinal microglia may direct to intensify pain in this model. Pain may be further
      amplified by reserpine-induced dysfunction of the descending pain inhibitory
      system and by the decrease in peripheral drive to this system resulting from a
      reduced proportion of mechanoresponsive C-nociceptors.

PMID- 25599241
TI  - Genetic insights toward improved management of chronic pain after mastectomy.

PMID- 25599240
TI  - Severity of chronic pain in an elderly population in Sweden--impact on costs and
      quality of life.
AB  - Chronic pain is associated with large societal costs, but few studies have
      investigated the total costs of chronic pain with respect to elderly subjects.
      The elderly usually require informal care, care performed by municipalities, and
      care for chronic diseases, all factors that can result in extensive financial
      burdens on elderly patients, their families, and the social services provided by
      the state. This study aims to quantify the societal cost of chronic pain in
      people of age 65 years and older and to assess the impact of chronic pain on
      quality of life. This study collected data from 3 registers concerning health
      care, drugs, and municipal services and from 2 surveys. A postal questionnaire
      was used to collect data from a stratified sample of the population 65 years and
      older in southeastern Sweden. The questionnaire addressed pain intensity and
      quality of life variables (EQ-5D). A second postal questionnaire was used to
      collect data from relatives of the elderly patients suffering from chronic pain.
      A total of 66.5% valid responses of the 10,000 subjects was achieved; 76.9% were
      categorized as having no or mild chronic pain, 18.9% as having moderate chronic
      pain, and 4.2% as having severe chronic pain. Consumed resources increased with
      the severity of chronic pain. Clear differences in EQ-5D were found with respect
      to the severity of pain. This study found an association between resource use and
      severity of chronic pain in elderly subjects: the more severe the chronic pain,
      the more extensive (and expensive) the use of resources.

PMID- 25599242
TI  - Postanaesthetic tear production and ocular irritation in cats.
AB  - OBJECTIVE: General anaesthesia significantly reduces tear production and normal
      values are not immediately re-established on ending anaesthesia. Therefore,
      adequate protection of the cornea has to be assured during the perianaesthetic
      period. There are various methods available, including taping of the eyelids and
      the application of eye ointments, gels and drops. In human medicine studies,
      different formulations were found to induce signs of ocular irritation. The aim
      of the present study was to determine tear production in cats after general
      anaesthesia, and to identify possible causes of irritation. MATERIAL AND METHODS:
      Tear production was determined in 41 cats after general anaesthesia and eyes were
      examined for signs of irritation. Two different anaesthetic protocols were used.
      To protect the cornea, an ointment and gel were applied to the right and left
      eyes, respectively. RESULTS: Postoperatively, tear production was significantly
      reduced for 6 hours and 18 hours in the right and left eyes, respectively. Two
      hours after anaesthesia, blepharospasm of the right eye was observed in 92.7% (n
      = 38) of the cats. In contrast, the left eye was always held open. CONCLUSIONS:
      This study demonstrated that tear production in cats is significantly decreased
      both during and after anaesthesia. The degree of reduction was independent of the
      anaesthetic protocol. Both the eye ointment and gel proved effective in
      protecting the corneal surface. However, eye gel use is recommended because the
      eye ointment consistently caused an irritation comparable to the foreign-body
      sensation reported in humans.

PMID- 25599238
TI  - Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic
      PPARgamma mechanisms.
AB  - Repeated administration of peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists reduces neuropathic pain-like behavior and associated
      changes in glial activation in the spinal cord dorsal horn. As PPARgamma is a
      nuclear receptor, sustained changes in gene expression are widely believed to be
      the mechanism of pain reduction. However, we recently reported that a single
      intrathecal (i.t.) injection of pioglitazone, a PPARgamma agonist, reduced
      hyperalgesia within 30 minutes, a time frame that is typically less than that
      required for genomic mechanisms. To determine the very rapid antihyperalgesic
      actions of PPARgamma activation, we administered pioglitazone to rats with spared
      nerve injury and evaluated hyperalgesia. Pioglitazone inhibited hyperalgesia
      within 5 minutes of injection, consistent with a nongenomic mechanism. Systemic
      or i.t. administration of GW9662, a PPARgamma antagonist, inhibited the
      antihyperalgesic actions of intraperitoneal or i.t. pioglitazone, suggesting a
      spinal PPARgamma-dependent mechanism. To further address the contribution of
      nongenomic mechanisms, we blocked new protein synthesis in the spinal cord with
      anisomycin. When coadministered intrathecally, anisomycin did not change
      pioglitazone antihyperalgesia at an early 7.5-minute time point, further
      supporting a rapid nongenomic mechanism. At later time points, anisomycin reduced
      pioglitazone antihyperalgesia, suggesting delayed recruitment of genomic
      mechanisms. Pioglitazone reduction of spared nerve injury-induced increases in
      GFAP expression occurred more rapidly than expected, within 60 minutes. We are
      the first to show that activation of spinal PPARgamma rapidly reduces neuropathic
      pain independent of canonical genomic activity. We conclude that acute
      pioglitazone inhibits neuropathic pain in part by reducing astrocyte activation
      and through both genomic and nongenomic PPARgamma mechanisms.

PMID- 25599243
TI  - Middle-ear pain and trauma during air travel.
AB  - INTRODUCTION: Changes in air pressure during flying can cause ear-drum pain and
      perforation, vertigo, and hearing loss. It has been estimated that 10% of adults
      and 22% of children might have changes to the ear drum after a flight, although
      perforation is rare. Symptoms usually resolve spontaneously. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical question: What are the effects of interventions to prevent middle-ear
      pain during air travel? We searched: Medline, Embase, The Cochrane Library and
      other important databases up to July 2014 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found three studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: nasal
      balloon inflation, nasal decongestants (topical), and oral pseudoephedrine.

PMID- 25599245
TI  - Effectiveness of cilostazol in the treatment of peripheral arterial obstruction.

PMID- 25599246
TI  - Tracking of Pedometer-Determined Physical Activity in Healthy Elderly Japanese
      People.
AB  - BACKGROUND: Tracking refers to the tendency for an individual to maintain their
      rank within a group over time. This study longitudinally investigated the 8-year
      tracking of pedometer-determined physical activity among physically independent
      elderly Japanese people aged 72 to 80 years. METHODS: Steps/day were measured
      when participants were aged 72 and assessed again after 2, 5, and 8 years. The
      number of participants with a 2-year follow-up (72 to 74 years) was 177 (101
      males, 76 females), with a 5-year follow-up (72 to 77 years) was 183 people (110
      males, 73 females), and with an 8-year follow-up (72 to 80 years) was 145 people
      (91 males, 54 females). Step counts were continuously measured for 1 week in
      January, April, July, and October during each year of assessment. RESULTS: A high
      rank correlation coefficient for steps/day exceeding 0.60 was obtained at the 2-,
      5- and 8-year follow-up examinations for both males and females. CONCLUSION: This
      study suggests that the rank within a group of pedometer-determined steps/day
      remains stable over up to 8 years in healthy Japanese people aged between 72 to
      80 years old.

PMID- 25599247
TI  - Validity of Pedometers to Measure Step Counts During Dance.
AB  - PURPOSE: To obtain validity evidence for the measurement of step counts by spring
      levered and piezoelectric pedometers during dance. METHODS: Thirty-five adults in
      a college dance class participated in this study. Participants completed trials
      of 3- and 5-min of different styles of dance wearing Walk4life MVP and Omron HJ
      303 pedometers, while their steps were visually counted. Pearson correlation,
      paired t-test, mean absolute percent error (MAPE), and mean bias were calculated
      between actual step and pedometer step counts for the 3- and 5-min dances
      separately. RESULTS: For the Walk4life trials the correlations were .92 and .77
      for the 3- and 5-min dances. No significant differences were shown by t-test for
      the 3- (P = .16) and 5-min dances (P = .60). However, MAPE was high, 17.7 +/-
      17.7% and 19.4 +/- 18.3% for the 2 dance durations, respectively. For the Omron,
      the correlations were .44 and .58 for the 3- and 5-min dances, respectively. No
      significant differences were shown by t-test for the 3-min (P = .38) and for the
      5-min (P = .88) dances. However, MAPE was high, 19.3 +/- 16.4% and 26.6 +/- 15.2%
      for the 2 dance durations, respectively. CONCLUSIONS: This study demonstrated
      that pedometers can be used to estimate the number of steps taken by a group of
      college students while dancing, however caution is necessary with individual
      values.

PMID- 25599244
TI  - Neighborhood Social Cohesion and Depressive Symptoms Among Latinos: Does Use of
      Community Resources for Physical Activity Matter?
AB  - BACKGROUND: Greater neighborhood social cohesion is linked to fewer depressive
      symptoms and greater physical activity, but the role of physical activity on the
      relationship between neighborhood social cohesion and depression is poorly
      understood. The purpose of the study was to examine the effects of physical
      activity on the association between neighborhood social cohesion and depressive
      symptoms. METHODS: Multivariate logistic regression tested the moderation of self
      reported leisure-time moderate-to-vigorous physical activity (LTMVPA) and active
      use of parks or recreational facilities on the association between neighborhood
      social cohesion and depressive symptoms among 295 randomly selected Latino adults
      who completed a face-to-face interview. RESULTS: After adjusting for age, gender,
      and income, neighborhood social cohesion and depressive symptoms were inversely
      related (OR = 0.8; 95% CI: 0.5-1.2). Active use of parks or recreational
      facilities moderated the association between neighborhood social cohesion and
      depressive symptoms but meeting the recommendations for LTMVPA did not. Latinos
      who reported active use of parks or recreational facilities and higher levels of
      neighborhood social cohesion had fewer depressive symptoms than peers who did not
      use these spaces. CONCLUSIONS: Future studies are needed to test strategies for
      promoting active use of parks or recreational facilities to address depression in
      Latinos.

PMID- 25599248
TI  - Automatic analysis and characterization of the hummingbird wings motion using
      dense optical flow features.
AB  - A new method for automatic analysis and characterization of recorded hummingbird
      wing motion is proposed. The method starts by computing a multiscale dense
      optical flow field, which is used to segment the wings, i.e., pixels with larger
      velocities. Then, the kinematic and deformation of the wings were characterized
      as a temporal set of global and local measures: a global angular acceleration as
      a time function of each wing and a local acceleration profile that approximates
      the dynamics of the different wing segments. Additionally, the variance of the
      apparent velocity orientation estimates those wing foci with larger deformation.
      Finally a local measure of the orientation highlights those regions with maximal
      deformation. The approach was evaluated in a total of 91 flight cycles, captured
      using three different setups. The proposed measures follow the yaw turn
      hummingbird flight dynamics, with a strong correlation of all computed paths,
      reporting a standard deviation of [Formula: see text] and [Formula: see text] for
      the global angular acceleration and the global wing deformation respectively. 

PMID- 25599249
TI  - Culturally responsive care in occupational therapy: an entry-level educational
      model embedded in service-learning.
AB  - OBJECTIVE: This study focuses on the design of an entry-level educational model
      of culturally responsive care in occupational therapy embedded in service
      learning (CRCOT-SL) that is perceived as clear, relevant, evidence-based, and
      useful by occupational therapy educators. The purpose of the model is to guide OT
      educators in teaching students to enable occupational participation and social
      inclusion in cross-cultural encounters. METHOD: The design consisted in defining
      the areas of the model and the components of each area, and articulating the
      learning process embedded in service-learning. A formative evaluation of CRCOT-SL
      was then performed using survey methods to collect feedback from 30 OT educators
      regarding the clarity, relevance, evidence-based constructs, and usefulness of
      CRCOT-SL. RESULTS: CRCOT-SL was perceived to be clear, relevant, evidence-based,
      and useful to 81.5% of the OT educators who participated in the study. Minor
      modifications to the model were completed based on the educator's feedback.
      CONCLUSIONS: CRCOT-SL is intended to respond not only to the dynamic,
      multicultural, and diverse environments in which practitioners currently practice
      but to the future needs of a global community facing social, political, economic,
      and environmental issues that will continue to affect dramatically people's
      living conditions and occupational needs.

PMID- 25599250
TI  - Standard dilution analysis.
AB  - Standard dilution analysis (SDA) is a novel calibration method that may be
      applied to most instrumental techniques that will accept liquid samples and are
      capable of monitoring two wavelengths simultaneously. It combines the traditional
      methods of standard additions and internal standards. Therefore, it
      simultaneously corrects for matrix effects and for fluctuations due to changes in
      sample size, orientation, or instrumental parameters. SDA requires only 200 s per
      sample with inductively coupled plasma optical emission spectrometry (ICP OES).
      Neither the preparation of a series of standard solutions nor the construction of
      a universal calibration graph is required. The analysis is performed by combining
      two solutions in a single container: the first containing 50% sample and 50%
      standard mixture; the second containing 50% sample and 50% solvent. Data are
      collected in real time as the first solution is diluted by the second one. The
      results are used to prepare a plot of the analyte-to-internal standard signal
      ratio on the y-axis versus the inverse of the internal standard concentration on
      the x-axis. The analyte concentration in the sample is determined from the ratio
      of the slope and intercept of that plot. The method has been applied to the
      determination of FD&C dye Blue No. 1 in mouthwash by molecular absorption
      spectrometry and to the determination of eight metals in mouthwash, wine, cola,
      nitric acid, and water by ICP OES. Both the accuracy and precision for SDA are
      better than those observed for the external calibration, standard additions, and
      internal standard methods using ICP OES. 

PMID- 25599251
TI  - Biological armors under impact--effect of keratin coating, and synthetic bio
      inspired analogues.
AB  - A number of biological armors, such as turtle shells, consist of a strong
      exoskeleton covered with a thin keratin coating. The mechanical role upon impact
      of this keratin coating has surprisingly not been investigated thus far. Low
      velocity impact tests on the turtle shell reveal a unique toughening phenomenon
      attributed to the thin covering keratin layer, the presence of which noticeably
      improves the fracture energy and shell integrity. Synthetic substrate/coating
      analogues were subsequently prepared and exhibit an impact behavior similar to
      the biological ones. The results of the present study may improve our
      understanding, and even future designs, of impact-tolerant structures. 

PMID- 25599252
TI  - Immunomodulatory effects of Lippia sidoides extract: induction of IL-10 through
      cAMP and p38 MAPK-dependent mechanisms.
AB  - Lippia sidoides is an aromatic shrub that grows wild in the northeastern region
      of Brazil. In local traditional medicine, the aerial portions of this species are
      used as anti-infectives, antiseptics, spasmolytics, sedatives, hypotensives, and
      anti-inflammatory agents. In this research, we evaluate the potential
      immunological properties of Lippia extract through in vitro analysis of its
      ability to modulate intracellular cyclic adenosine monophosphate (cAMP) levels
      and interleukin-10 (IL-10) production. These results show that Lippia extract
      increases intracellular cAMP through the inhibition of phosphodiesterase
      activity. They also demonstrate that Lippia extract increases IL-10 production in
      THP-1 monocytes through both an increase in intracellular cAMP and the activation
      of p38 MAPK. These results suggest that the Lippia-mediated inhibition of
      phosphodiesterase activity and the subsequent increase in intracellular cAMP may
      explain some of the biological activities associated with L. sidoides. In
      addition, the anti-inflammatory activity of L. sidoides may also be due, in part,
      to its ability to induce IL-10 production through the inhibition of cyclic
      nucleotide-dependent phosphodiesterase activity and by its activation of the p38
      MAPK pathway. 

PMID- 25599253
TI  - A silver bullet: elemental silver as an efficient reducing agent for atom
      transfer radical polymerization of acrylates.
AB  - Elemental silver was used as a reducing agent in the atom transfer radical
      polymerization (ATRP) of acrylates. Silver wire, in conjunction with a
      CuBr(2)/TPMA catalyst, enabled the controlled, rapid preparation of polyacrylates
      with dispersity values down to D = 1.03. The silver wire in these reactions was
      reused several times in sequential reactions without a decline in performance,
      and the amount of copper catalyst used was reduced to 10 ppm without a large
      decrease in control. A poly(n-butyl acrylate)-block-poly(tert-butyl acrylate)
      diblock copolymer was synthesized with a molecular weight of 91 400 and D = 1.04,
      demonstrating good retention of chain-end functionality and a high degree of
      livingness in this ATRP system.

PMID- 25599254
TI  - Retrospective coping strategies during sexual identity formation and current
      biopsychosocial stress.
AB  - BACKGROUND: Lesbian, gay men, and bisexual individuals (LGBs) often experience
      distress related to the recognition, self-acceptance, and disclosure of their
      sexual orientation. OBJECTIVES AND DESIGN: Retrospectively reported coping
      strategies enacted during sexual identity formation among LGBs were assessed in
      relation to current stress indices measured using environmental (frequency of
      perceived daily hassles), psychological (perceived distress), and biological
      (allostatic load [AL] levels representing physiological dysregulations)
      perspectives. METHODS: Forty-six healthy LGBs between the ages of 18 and 45 (M =
      23.91, SE = .80) participated. Questionnaires included the Ways of Coping
      Checklist adapted to disclosure milestones, Daily Hassles Inventory, and
      Perceived Stress Scale. AL was calculated using 21 biomarkers of neuroendocrine,
      immune, cardiovascular, and metabolic functioning. RESULTS: Avoidance coping
      during sexual identity formation was positively associated with frequency of
      daily hassles (beta = .598, p < .001), perceived stress (beta = .361, p = .015),
      and AL (beta = .405, p = .006). By contrast, seeking social support was
      negatively associated with perceived stress (beta = -.598, p = .048).
      CONCLUSIONS: Emotion-focused coping strategies during LGB sexual identity
      development are associated with current indices of biopsychosocial stress.

PMID- 25599256
TI  - Solvent-Controlled Excited State Relaxation Path of 4-Acetyl-4'
      (dimethylamino)biphenyl.
AB  - Stationary and picosecond time-resolved fluorescence (TRF) and absorption spectra
      were compared in different aprotic solvents at various temperatures for 4-acetyl
      4'-(dimethylamino)biphenyl (ADAB). A large value of the excited state dipole
      moment, 18-25 D, was estimated from the plot of solvatochromic shift. TRF spectra
      of ADAB recorded as a function of solvent polarity and temperature show unusual
      temporal evolution (shift and decay) of the fluorescence bands. In some cases,
      the dynamic Stokes shifts occur on a time scale much shorter than expected on the
      basis of literature data on solvent relaxation. In order to investigate
      variations in the energy of electronic transitions, oscillator strengths, and
      dipole moments upon changing the molecular geometry, quantum chemical modeling
      (DFT, TD-DFT, CIS) was performed for ADAB and its ground-state pretwisted
      derivative, 4-acetyl-4'-dimethylamino-2,2'-dimethylbiphenyl (ADAB-Me).
      Combination of spectroscopic data and computational results leads to the model of
      excited state relaxation which involves dynamic solvent-dependent interaction
      between two close-lying (1)npi* and (1)pipi* excited electronic states. 

PMID- 25599257
TI  - Risk factors for unwanted pregnancy and subsequent abortion among women aged 16
      to 25 years in Latvia.
AB  - OBJECTIVE: To investigate the risk factors associated with unwanted pregnancy in
      16- to 25-year-old women in Latvia. METHODS: Case-control study of 16- to 25-year
      old, sexually active women who did not want to get pregnant: the cases were 144
      women who underwent their first abortion whereas 278 nulliparous women served as
      controls. Data concerning them were obtained by using a semi-structured anonymous
      questionnaire that included questions about education, sexual life habits,
      contraceptive practice and a multiple-choice test to assess knowledge about
      contraception. RESULTS: Women who underwent an abortion had had more lifetime
      sexual partners, had more often not used any contraception, and were
      significantly less knowledgeable about the latter than controls. No strong
      correlation between knowledge and actual contraceptive practice was observed in
      the study groups. Logistic regression analysis showed that the most significant
      risk factors were non-use of contraception or use of less effective methods.
      CONCLUSIONS: The risk of unwanted pregnancy was associated with the woman's
      behaviour; her knowledge of contraception was much less relevant. Sexual health
      programmes should focus more on intrapersonal and interpersonal factors to
      promote use of effective contraception among young women.

PMID- 25599259
TI  - Trends in web-based HIV behavioural surveillance among gay and bisexual men in
      New Zealand: complementing location-based surveillance.
AB  - Most HIV behavioural surveillance programmes for gay, bisexual and other men who
      have sex with men (MSM) sample from location-based (offline) or web-based
      (online) populations, but few combine these two streams. MSM sampled online have
      been found to differ demographically and behaviourally from those sampled
      offline, meaning trends identified in one system may not hold for the other. The
      aim was to examine trends among MSM responding to supplementary repeat online
      behavioural surveillance surveys who had not participated in offline surveillance
      earlier that year in the same city, to see whether trends were parallel,
      converged or diverged. We recruited a total of 1613 MSM from an Internet dating
      site in Auckland, New Zealand in 2006, 2008 and 2011 using identical
      questionnaires and eligibility criteria to offline surveillance. Condom use was
      stable over time, HIV testing rates rose, the proportion reporting over 20 recent
      male partners declined, and anal intercourse rates increased, consistent with
      trends in offline surveillance conducted concomitantly and reported elsewhere.
      Variant trends included greater stability in condom use with casual partners
      among online-recruited MSM, and a rise in regular fuckbuddy partnering not
      identified among offline-recruited MSM. Among MSM recruited online, the frequency
      of checking Internet dating profiles increased between 2008 and 2011. In
      conclusion, supplementary web-based behavioural surveillance among MSM generally
      corroborates trends identified in offline surveillance. There are however some
      divergent trends, that would have been overlooked if only one form of
      surveillance had been conducted. As MSM populations increasingly shift their
      socialising patterns online and diversify, multiple forms of HIV behavioural
      monitoring may be required. 

PMID- 25599260
TI  - HPLC-Q-TOF-MS identification of antioxidant and antihypertensive peptides
      recovered from cherry (Prunus cerasus L.) subproducts.
AB  - The processing of fruits, such as cherries, is characterized by generating a lot
      of waste material such as fruit stones, skins, etc. To contribute to
      environmental sustainability, it is necessary to recover these residues. Cherry
      stones contain seeds with a significant amount of proteins that are underused and
      undervalued. The aim of this work was to extract cherry seed proteins, to
      evaluate the presence of bioactive peptides, and to identify them by mass
      spectrometry. The digestion of cherry seed proteins was optimized, and three
      different enzymes were employed: Alcalase, Thermolysin, and Flavourzyme. Peptide
      extracts obtained by the digestion of the cherry seed protein isolate with
      Alcalase and Thermolysin yielded the highest antioxidant and antihypertensive
      capacities. Ultrafiltration of hydrolysates allowed obtaining fractions with high
      antioxidant and antihypertensive capabilities. HPLC-Q-TOF-MS together with
      bioinformatics tools enabled one to identify peptides in these fractions.

PMID- 25599261
TI  - Transcranial direct current stimulation enhances mu rhythm desynchronization
      during motor imagery that depends on handedness.
AB  - Transcranial direct current stimulation (tDCS) can modulate the amplitude of
      event-related desynchronization (ERD) that appears on the electroencephalogram
      (EEG) during motor imagery. To study the effect of handedness on the modulating
      effect of tDCS, we compared the difference in tDCS-boosted ERD during dominant
      and non-dominant hand motor imagery. EEGs were recorded over the left
      sensorimotor cortex of seven healthy right-handed volunteers, and we measured ERD
      induced either by dominant or non-dominant hand motor imagery. Ten minutes of
      anodal tDCS was then used to increase the cortical excitability of the
      contralateral primary motor cortex (M1), and ERD was measured again. With anodal
      tDCS, we observed only a small increase in ERD during non-dominant hand motor
      imagery, whereas the same stimulation induced a prominent increase in ERD during
      dominant hand motor imagery. This trend was most obvious in the participants who
      used their dominant hand more frequently. Although our study is preliminary
      because of a small sample size, these results suggest that the increase in ERD by
      applying anodal tDCS was stronger on the dominant side than on the non-dominant
      side. The background excitability of M1 may determine the strength of the effect
      of anodal tDCS on ERD by hand motor imagery. 

PMID- 25599262
TI  - Evaluation of CO2-philicity of poly(vinyl acetate) and poly(vinyl acetate-alt
      maleate) copolymers through molecular modeling and dissolution behavior
      measurement.
AB  - Multiscale molecular modeling and dissolution behavior measurement were both used
      to evaluate the factors conclusive on the CO2-philicity of poly(vinyl acetate)
      (PVAc) homopolymer and poly(vinyl acetate-alt-maleate) copolymers. The ab initio
      calculated interaction energies of the candidate CO2-philic molecule models with
      CO2, including vinyl acetate dimer (VAc), dimethyl maleate (DMM), diethyl maleate
      (DEM), and dibutyl maleate (DBM), showed that VAc was the most CO2-philc segment.
      However, the cohesive energy density, solubility parameter, Flory-Huggins
      parameter, and radial distribution functions calculated by using the molecular
      dynamics simulations for the four polymer and polymer-CO2 systems indicated that
      poly(VAc-alt-DBM) had the most CO2-philicity. The corresponding polymers were
      synthesized by using free radical polymerization. The measurement of cloud point
      pressures of the four polymers in CO2 also demonstrated that poly(VAc-alt-DBM)
      had the most CO2-philicity. Although copolymerization of maleate, such as DEM or
      DBM, with PVAc reduced the polymer-CO2 interactions, the weakened polymer-polymer
      interaction increased the CO2-philicity of the copolymers. The polymer-polymer
      interaction had a significant influence on the CO2-philicity of the polymer.
      Reduction of the polymer-polymer interaction might be a promising strategy to
      prepare the high CO2-philic polymers on the premise that the strong polymer-CO2
      interaction could be maintained. 

PMID- 25599263
TI  - Novel potential treatment modalities for ocular hypertension: focus on
      angiotensin and bradykinin system axes.
AB  - Despite the availability of modern surgical procedures, new drug delivery
      techniques, health authority-approved single topical ocular drugs, and
      combination products thereof, there continues to be an unmet medical need for
      novel treatment modalities for preserving vision. This is especially true for the
      treatment of glaucoma and the high risk factor often associated with this ocular
      disease, elevated intraocular pressure (IOP). Undesirable local or systemic side
      effects, frequency of dosing, lack of sustained IOP lowering, and lack of
      prevention of diurnal IOP spikes are among the greatest challenges. The very
      recent discovery, characterization, and publication of 2 novel IOP-lowering
      agents that pertain to the renin-angiotensin and kallikrein-kinin axes
      potentially offer novel means to treat and control ocular hypertension (OHT).
      Here, some contextual introductory information is provided first, followed by
      more detailed discussion of the properties and actions of diminazene aceturate
      (DIZE; a novel angiotensin-converting enzyme-2 activator) and FR-190997 (a
      nonpeptide bradykinin receptor-2 agonist) in relation to their anti-OHT
      activities in rodent and cynomolgus monkey eyes, respectively. It is anticipated
      that these compounds will pave the way for future discovery, development, and
      marketing of novel drugs to treat glaucoma and thus help save sight for millions
      of people afflicted with this slow progressive optic neuropathy. 

PMID- 25599265
TI  - Kinematic Patterns Associated with the Vertical Force Produced during the
      Eggbeater Kick.
AB  - The purpose of this study was to determine the kinematic patterns that maximized
      the vertical force produced during the water polo eggbeater kick. Twelve water
      polo players were tested executing the eggbeater kick with the trunk aligned
      vertically and with the upper limbs above water while trying to maintain as high
      a position as possible out of the water for nine eggbeater kick cycles. Lower
      limb joint angular kinematics, pitch angles and speed of the feet were
      calculated. The vertical force produced during the eggbeater kick cycle was
      calculated using inverse dynamics for the independent lower body segments and
      combined upper body segments, and a participant-specific second-degree regression
      equation for the weight and buoyancy contributions. Vertical force normalized to
      body weight was associated with hip flexion (average, r = 0.691; maximum, r =
      0.791; range of motion, r = 0.710), hip abduction (maximum, r = 0.654), knee
      flexion (average, r = 0.716; minimum, r = 0.653) and knee flexion-extension
      angular velocity (r = 0.758). Effective orientation of the hips resulted in fast
      horizontal motion of the feet with positive pitch angles. Vertical motion of the
      feet was negatively associated with vertical force. A multiple regression model
      comprising the non-collinear variables of maximum hip abduction, hip flexion
      range of motion and knee flexion angular velocity accounted for 81% of the
      variance in normalized vertical force. For high performance in the water polo,
      eggbeater kick players should execute fast horizontal motion with the feet by
      having large abduction and flexion of the hips, and fast extension and flexion of
      the knees. 

PMID- 25599264
TI  - Detecting Functional Connectivity During Audiovisual Integration with MEG: A
      Comparison of Connectivity Metrics.
AB  - In typical magnetoencephalography and/or electroencephalography functional
      connectivity analysis, researchers select one of several methods that measure a
      relationship between regions to determine connectivity, such as coherence, power
      correlations, and others. However, it is largely unknown if some are more suited
      than others for various types of investigations. In this study, the authors
      investigate seven connectivity metrics to evaluate which, if any, are sensitive
      to audiovisual integration by contrasting connectivity when tracking an
      audiovisual object versus connectivity when tracking a visual object uncorrelated
      with the auditory stimulus. The authors are able to assess the metrics'
      performances at detecting audiovisual integration by investigating connectivity
      between auditory and visual areas. Critically, the authors perform their
      investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced
      in seed selection. The authors find that amplitude-based connectivity measures in
      the beta band detect strong connections between visual and auditory areas during
      audiovisual integration, specifically between V4/V5 and auditory cortices in the
      right hemisphere. Conversely, phase-based connectivity measures in the beta band
      as well as phase and power measures in alpha, gamma, and theta do not show
      connectivity between audiovisual areas. The authors postulate that while beta
      power correlations detect audiovisual integration in the current experimental
      context, it may not always be the best measure to detect connectivity. Instead,
      it is likely that the brain utilizes a variety of mechanisms in neuronal
      communication that may produce differential types of temporal relationships. 

PMID- 25599266
TI  - Audio-visual integration and saccadic inhibition.
AB  - Saccades operate a continuous selection between competing targets at different
      locations. This competition has been mostly investigated in the visual context,
      and it is well known that a visual distractor can interfere with a saccade toward
      a visual target. Here, we investigated whether multimodal, audio-visual targets
      confer stronger resilience against visual distraction. Saccades to audio-visual
      targets had shorter latencies than saccades to unisensory stimuli. This
      facilitation exceeded the level that could be explained by simple probability
      summation, indicating that multisensory integration had occurred. The magnitude
      of inhibition induced by a visual distractor was comparable for saccades to
      unisensory and multisensory targets, but the duration of the inhibition was
      shorter for multimodal targets. We conclude that multisensory integration can
      allow a saccade plan to be reestablished more rapidly following saccadic
      inhibition. 

PMID- 25599267
TI  - Commission errors of active intentions: the roles of aging, cognitive load, and
      practice.
AB  - Performing an intended action when it needs to be withheld, for example, when
      temporarily prescribed medication is incompatible with the other medication, is
      referred to as commission errors of prospective memory (PM). While recent
      research indicates that older adults are especially prone to commission errors
      for finished intentions, there is a lack of research on the effects of aging on
      commission errors for still active intentions. The present research investigates
      conditions which might contribute to older adults' propensity to perform planned
      intentions under inappropriate conditions. Specifically, disproportionally higher
      rates of commission errors for still active intentions were observed in older
      than in younger adults with both salient (Experiment 1) and non-salient
      (Experiment 2) target cues. Practicing the PM task in Experiment 2, however,
      helped execution of the intended action in terms of higher PM performance at
      faster ongoing-task response times but did not increase the rate of commission
      errors. The results have important implications for the understanding of older
      adults' PM commission errors and the processes involved in these errors. 

PMID- 25599268
TI  - Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after
      Traumatic Central Nervous System Injury.
AB  - Endogenous neural progenitor cell niches have been identified in adult mammalian
      brain and spinal cord. Few studies have examined human spinal cord tissue for a
      neural progenitor cell response in disease or after injury. Here, we have
      compared cervical spinal cord sections from 14 individuals who died as a result
      of nontraumatic causes (controls) with 27 who died from injury with evidence of
      trauma to the central nervous system. Nestin immunoreactivity was used as a
      marker of neural progenitor cell response. There were significant increases in
      the percentage of ependymal cells that were nestin positive between controls and
      trauma cases. When sections from lumbar and thoracic spinal cord were available,
      nestin positivity was seen at all three spinal levels, suggesting that nestin
      reactivity is not simply a localized reaction to injury. There was a positive
      correlation between the percentage of ependymal cells that were nestin positive
      and post-injury survival time but not for age, postmortem delay, or glial
      fibrillary acidic protein (GFAP) immunoreactivity. No double-labelled nestin and
      GFAP cells were identified in the ependymal, subependymal, or parenchymal regions
      of the spinal cord. We need to further characterize this subset of ependymal
      cells to determine their role after injury, whether they are a population of
      neural progenitor cells with the potential for proliferation, migration, and
      differentiation for spinal cord repair, or whether they have other roles more in
      line with hypothalamic tanycytes, which they closely resemble. 

PMID- 25599269
TI  - Alcohol abuse management in primary care: an e-learning course.
AB  - BACKGROUND: The mental health knowledge gap challenges public health. The Alcohol
      Abuse Management in Primary Care (AAMPC) is an e-learning course designed to
      cover alcohol-related problems from the primary care perspective. The goal of
      this study was to verify if the AAMPC was able to enhance healthcare
      professionals' alcohol-related problems knowledge. MATERIALS AND METHODS: One
      hundred subscriptions for the AAMPC were offered through the federal telehealth
      program. The course was instructor-led and had nine weekly classes, delivered
      synchronously or asynchronously, at the students' convenience, using a varied
      array of learning tools. At the beginning, students took a test that provided a
      positive score, related to critical knowledge for clinical management, and a
      negative score, related to misconceptions about alcohol-related problems. The
      test was repeated 2 months after course completion. RESULTS: Thirty-three
      students completed the course. The positive score improved significantly
      (p<0.001), but not the negative score. Students with previous experience with e
      courses presented greater improvement on the positive score (p<0.036). Eighty
      percent of the students thought the course excelled in meeting its objectives.
      Web conferences and video and audio recordings were the most appreciated learning
      tools. Course satisfaction was negatively related to frequency of Internet access
      (Spearman's rho=-0.455, p=0.022). CONCLUSIONS: E-learning was highly appreciated
      as a learning tool, especially by students with the least frequency of Internet
      use. Nonetheless, it worked better for those previously familiar with e-courses.
      The AAMPC e-course provided effective knowledge transmission and retention.
      Complementary strategies to reduce misconceptions about alcohol-related problems
      must be developed for the training of primary care staff.

PMID- 25599270
TI  - Autologous-conditioned serum: evidence for use in the knee.
AB  - Since the first description of autologous-conditioned serum (ACS) almost two
      decades ago, there has been a presumption of beneficial proteins found within
      this product. Thought to be a key protein in ACS, interleukin 1 receptor
      antagonist (IL-1Ra) has received the majority of the attention; although the
      extent of biological proteins is not known and likely because of the autologous
      nature of the product, vary from individual to individual. Following the positive
      anecdotal evidence, preclinical data demonstrated both symptom and disease
      modifying effects. These results were followed by two randomized placebo
      controlled clinical trials, both showing significant improvement compared with
      placebo or hyaluronan acid in one study for quality of life, pain, and patient
      assessed efficacy when ACS was administered in the human knee. Much is still
      unknown regarding the key active proteins found in ACS as well as definitive
      dosing, frequency, and administration time postinjury, which hopefully will be
      the focus of future studies. 

PMID- 25599271
TI  - Ring expansion reactions of pentaphenylborole with dipolar molecules as a route
      to seven-membered boron heterocycles.
AB  - Reactions of pentaphenylborole with isocyanates, benzophenone, and benzaldehyde
      produced new seven-membered heterocycles in high yields. For 1-adamantyl
      isocyanate, a BNC5 heterocycle was obtained from the insertion of the C-N moiety
      into the five-membered borole, whereas for 4-methoxyphenyl isocyanate, a BOC5
      heterocycle was generated from the insertion of the C-O unit. These reactions are
      believed to occur via a mechanism wherein coordination of the nucleophile to the
      borole (1-adamantyl, N-coordination or O-coordination for 4-methoxyphenyl) is
      followed by ring expansion to afford the observed seven-membered heterocycles.
      The selectivity to form B-O- or B-N-containing heterocycles is based on the
      polarization of the isocyanate implying tunable reactivity for the system. Having
      observed that isocyanates react as 1,2-dipoles with pentaphenylborole, we
      examined benzophenone and benzaldehyde, which both reacted to insert C-O units
      into the ring. This represents a new efficient method for preparing rare seven
      membered boracycles. 

PMID- 25599272
TI  - Current controversies in sports nutrition.

PMID- 25599273
TI  - Antifungal Activity of Some Constituents of Origanum vulgare L. Essential Oil
      Against Postharvest Disease of Peach Fruit.
AB  - Plant essential oils (EOs) can potentially replace synthetic fungicides in the
      management of postharvest fruit and vegetable diseases. The aim of this study was
      to evaluate in vitro and in vivo effectiveness of thymol, carvacrol, linalool,
      and trans-caryophyllene, single constituents of the EO of Origanum vulgare L.
      ssp. hirtum against Monilinia laxa, M. fructigena, and M. fructicola, which are
      important phytopathogens and causal agents of brown rot of pome and stone fruits
      in pre- and postharvest. Moreover, the possible phytotoxic activity of these
      constituents was assessed and their minimum inhibitory concentration (MIC) was
      determined. In vitro experiment indicated that thymol and carvacrol possess the
      highest antifungal activity. Results of in vivo trials confirmed the strong
      efficacy of thymol and carvacrol against brown rot of peach fruits. The thymol
      MIC resulted to be 0.16 MUg/MUL against M. laxa and M. fructigena and 0.12
      MUg/MUL against M. fructicola, whereas for carvacrol they were 0.02 MUg/MUL
      against the first two Monilinia species and 0.03 MUg/MUL against the third.
      Results of this study indicated that thymol and carvacrol could be used after
      suitable formulation for controlling postharvest fruit diseases caused by the
      three studied Monilinia species. 

PMID- 25599274
TI  - Tree nut consumption is associated with better nutrient adequacy and diet quality
      in adults: National Health and Nutrition Examination Survey 2005-2010.
AB  - Nutrient adequacy of tree nut consumers has not been examined. The National
      Health and Nutrition Examination Survey 2005-2010 data were used to assess the
      association of tree nut consumption by adults 19+ years (n = 14,386) with
      nutrient adequacy and diet quality. Covariate adjusted usual intake was
      determined using two 24-h dietary recalls and the National Cancer Institute
      method. Percentages of the consumption groups below the Estimated Average
      Requirement (EAR) or above the Adequate Intake (AI) were determined. Diet quality
      was determined using the Healthy Eating Index-2005 (HEI) score. Usual intake data
      showed consumers of tree nuts had a lower percentage (p < 0.0001) of the
      population below the EAR for vitamins A (22 +/- 5 vs. 49 +/- 1), E (38 +/- 4 vs.
      94 +/- 0.4) and C (17 +/- 4 vs. 44 +/- 1); folate (2.5 +/- 1.5 vs. 12 +/- 0.6);
      calcium (26 +/- 3 vs. 44 +/- 1); iron (3 +/- 0.6 vs. 9 +/- 0.4); magnesium (8 +/-
      1 vs. 60 +/- 1); and zinc (1.5 +/- 1 vs. 13 +/- 1). Tree nut consumers had a
      higher percentage (p < 0.0001) of the population above the AI for fiber (33 +/- 3
      vs. 4 +/- 0.3) and potassium (12 +/- 3 mg vs. 2 +/- 0.2 mg). HEI-2005 total score
      was higher (p < 0.0001) in tree nut consumers (61 +/- 0.7 vs. 52 +/- 0.3) than
      non-consumers. Health professionals should encourage the use of tree nuts as part
      of a dietary approach to healthy eating. 

PMID- 25599275
TI  - The effect on selenium concentrations of a randomized intervention with fish and
      mussels in a population with relatively low habitual dietary selenium intake.
AB  - Selenium status of the Danish population is below that assumed optimal for the
      suggested protective effects against chronic diseases, including certain cancers.
      Fish and shellfish are important dietary sources of selenium in Denmark. We
      investigated the effect of increased fish and mussel intake on selenium blood
      concentrations in a population with relatively low habitual dietary selenium
      intake. We randomly assigned 102 healthy men and women (all non-smokers) aged 48
      76 years to an intervention group (n = 51) or a control group (n = 51).
      Intervention participants received 1000 g fish and mussels/week for 26 weeks (~50
      MUg selenium/day). Controls received no intervention. Non-fasting blood samples
      were taken and whole blood selenium was determined using inductively coupled
      plasma-mass spectrometry (ICP-MS), and plasma selenoprotein P (SelP) was
      determined by high performance liquid chromatography coupled to ICP-MS. All
      available observations were included in linear multiple regression analysis to
      evaluate the effect of the intervention. The difference in mean change for
      intervention compared with control persons was 14.9 ng/mL (95% CI: 10.2, 19.7)
      for whole blood selenium, and 7.0 ng/mL (95% CI: 3.1, 10.9) for plasma SelP
      (Weeks 0-26). Selenium concentrations were significantly increased after 26 weeks
      of intervention, albeit to a lower degree than expected.

PMID- 25599276
TI  - Proposed therapeutic strategy for adult low-grade glioma based on aggressive
      tumor resection.
AB  - OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The
      authors hypothesized that adjuvant therapy might not be necessary for LGG cases
      in which total radiological resection was achieved. Accordingly, they established
      a treatment strategy based on the extent of resection (EOR) and the MIB-1 index:
      patients with a high EOR and low MIB-1 index were observed without postoperative
      treatment, whereas those with a low EOR and/or high MIB-1 index received
      radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the
      authors reviewed clinical data on patients with primarily diagnosed LGGs who had
      been treated according to the above-mentioned strategy, and they validated the
      treatment policy. Given their results, they will establish a new treatment
      strategy for LGGs stratified by EOR, histological subtype, and molecular status.
      METHODS One hundred fifty-three patients with diagnosed LGG who had undergone
      resection or biopsy at Tokyo Women's Medical University between January 2000 and
      August 2010 were analyzed. The patients consisted of 84 men and 69 women, all
      with ages >= 15 years. A total of 146 patients underwent surgical removal of the
      tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea
      based chemotherapy were administered in 48 and 35 patients, respectively. Extent
      of resection was significantly associated with both overall survival (OS; p =
      0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse
      astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy
      significantly prolonged PFS, especially in patients with oligodendroglial
      subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer
      OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as
      prognostic factors, but it did identify chemotherapy as a prognostic factor for
      PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings
      demonstrated that EOR was significantly correlated with patient survival; thus,
      one should aim for maximum tumor resection. In addition, patients with a higher
      EOR can be safely observed without adjuvant therapy. For patients with partial
      resection, postoperative chemotherapy should be administered for those with
      oligodendroglial subtypes, and repeat resection should be considered for those
      with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be
      required for patients with a poor prognosis, such as those with diffuse
      astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors
      with partial resection. 

PMID- 25599277
TI  - Editorial: the management of low-grade glioma in adults.

PMID- 25599278
TI  - Post-abortion contraception choices of women in Ghana: a one-year review.
AB  - Low rates of contraception in much of sub-Saharan Africa result in unplanned
      pregnancies, which in young, unmarried women often result in unsafe abortion.
      Increasing the use of highly effective forms of contraception has the potential
      to reduce the abortion-related mortality and morbidity. In this cross-sectional
      study, information collected by the post-abortion family planning counsellor was
      analysed. De-identified data from one year (June 2012-May 2013) were extracted
      from the logbook. Multivariate linear and logistic regression was performed. A
      total of 612 women received care for post-abortion complications from June 2012
      to May 2013. Young, unmarried women, and those who were being treated for
      complications arising from an induced versus spontaneous abortion were more
      likely to report they would use 'abstinence' as their method of contraception
      following their treatment. This vulnerable group could benefit from an increased
      uptake of long-acting reversible contraceptive methods to avoid repeated
      unplanned pregnancies and the potential of future unsafe abortions. 

PMID- 25599279
TI  - Impact of macro-level socio-economic factors on rising suicide rates in South
      Korea: panel-data analysis in East Asia.
AB  - BACKGROUND: The rapid increase in suicide rates in South Korea, particularly in
      the aftermath of the Asian economic crisis in the late 1990s, compares with the
      declining suicide rates observed in most other OECD countries over the same
      period. AIMS OF THE STUDY: This study aimed to examine an array of macro-level
      societal factors that might have contributed to the rising suicide trend in South
      Korea. METHODS: We first investigated whether this trend was unique to South
      Korea, or ubiquitous across five Asian countries/areas that are geographically
      and culturally similar (South Korea, Hong Kong, Japan, Singapore, and Taiwan),
      using WHO mortality data and national statistics (1980-2009). Age-standardised
      suicide rates (per 100,000 population) were calculated for each gender and age
      group (15-24, 25-44, 45-64, and 65+) for each country. Both panel data and
      country-specific time-series analyses were employed to investigate the impact of
      economic change and social integration/regulation on suicide. RESULTS: Despite
      similarities in geography and culture, the rising trend of suicide rates was
      unique to South Korea. This atypical trend was most apparent for people aged 65
      and over, which was in sharp contrast to the decreasing suicide trends observed
      in the other four Asian countries. The results of the panel data analyses
      generally pointed to a negative relationship between economic growth and suicide
      rates, particularly for working-aged people. The results of the time-series
      analyses further suggested that low levels of social integration, as indicated by
      rising divorce rates, may also have a role in rising suicide rates in South
      Korea, particularly for older people. Furthermore, the association between
      suicide rates and economic adversity (unemployment and economic downturn) was
      most salient among middle-aged men in South Korea. DISCUSSION AND LIMITATIONS:
      Compared to four other East Asian countries/areas (Hong Kong, Japan, Singapore,
      and Taiwan), South Korea has uniquely experienced a rising trend of suicide rates
      over the past three decades, particularly among older people. The findings
      highlight the differential associations between social changes and suicide rates
      at various stages over a person's life course. Low levels of social integration
      and economic adversity may in part explain the atypical suicide trend in South
      Korea, especially for older people and middle-aged men, respectively. Data
      constraints, however, limit the scope for explanation in light of the complex and
      multifactorial causes of suicide. IMPLICATIONS FOR HEALTH AND SOCIAL CARE
      POLICIES: Different age groups within the population require different policy
      interventions to curb the unprecedented rise in suicide rates in South Korea.
      Particularly for older people, there is a great need to strengthen methods of
      assisting family support as well as formulating models of social care that are
      financially-sustainable and culturally sensitive. More investment is also needed
      to strengthen labour market protection and/or expand social safety net for the
      unemployed. IMPLICATIONS FOR FURTHER RESEARCH: The link between social
      integration and suicide rates deserves further empirical investigation, so that
      mediating factors that are amenable to policy actions can be better identified.

PMID- 25599280
TI  - Choice of generic versus brand-name antidepressants in a regulated prescription
      drug market: evidence from Taiwan.
AB  - BACKGROUND: A health care system in which there is no separation between
      prescription and dispensation, combined with a regulated prescription drug
      market, leads to various generic substitution mechanisms for antidepressants.
      AIMS OF THE STUDY: We investigated the determinants of generic versus brand-name
      antidepressant choices in a regulated prescription market where physicians both
      prescribe and dispense drugs. METHODS: Using data from a sample of one million
      individuals selected randomly from the registry of National Health Insurance
      beneficiaries in 2010, and all claims for these one million enrollees between
      January 1997 and December 2011, we employed logistic regression to examine the
      choice of generic versus brand-name antidepressants in the Taiwanese prescription
      drug market. RESULTS: Access to various antidepressant brands varies according to
      the accreditation level and type of ownership of the healthcare provider. Private
      healthcare providers and those with lower accreditation levels were more likely
      to prescribe generic antidepressants compared to their brand-name counterparts.
      The diversity of products and competition in the molecule market was positively
      associated with the probability of prescribing generic antidepressants.
      DISCUSSION: In a regulated prescription drug market with no separation between
      prescription and dispensation, the substitution of generic antidepressant
      prescriptions in place of brand-name prescriptions is likely driven by drug and
      provider market characteristics, rather than by lowering costs. IMPLICATIONS FOR
      HEALTHCARE PROVISION: The allocation of different types of ownership and
      accreditation levels of healthcare providers may lead to unequal access to
      various brands of antidepressants. IMPLICATIONS FOR HEALTH POLICIES: Policies for
      improving the treatment of depression should take into account the structure of
      molecule and provider markets as important factors in determining the choice and
      utilization of antidepressants, in a healthcare system where physicians both
      prescribe and dispense drugs. IMPLICATIONS FOR FUTURE RESEARCH: Other
      psychotropic drug classes should be investigated to explore the effect of
      molecule and provider characteristics on the utilization of various classes of
      medication.

PMID- 25599281
TI  - Mental health inpatient treatment expenditure trends in China, 2005-2012:
      evidence from Shandong.
AB  - BACKGROUND: Mental health is increasingly becoming a huge public health issue in
      China. Yet for various cultural, healthcare system, and social economic reasons,
      people with mental health need have long been under-served in China. In order to
      inform the current on-going health care reform, empirical evidences on the
      economic burden of mental illnesses in China are urgently needed to contribute to
      health policy makers' understanding of the potential benefits to society from
      allocating more resources to preventing and treating mental illness. However, the
      cost of mental illnesses and particularly its trend in China remains largely
      unknown. AIMS OF THE STUDY: To investigate the trend of health care resource
      utilization among inpatients with mental illnesses in China, and to analyze what
      are the factors influencing the inpatient costs. METHOD: Our study sample
      included 15,721 patients, both adults and children, who were hospitalized over an
      eight-year period (2005-2012) in Shandong Center for Mental Health (SCMH), the
      only provincial psychiatric hospital in Shandong province, China. Data were
      extracted from the Health Information System (HIS) at SCMH, with detailed and
      itemized cost data on all inpatient expenses incurred during hospitalization. The
      identification of the patients was based on the ICD-10 diagnoses recorded in the
      HIS. Descriptive analysis was done to analyze the trend of hospitalization cost
      and length of stay during the study period. Multivariate stepwise regression
      analysis was conducted to assess the factors that influence hospitalization cost.
      RESULTS: Among the inpatients in our sample, the most common mental disorders
      were schizophrenia, schizotypal and delusional disorders. The disease which had
      the highest per capita hospital expense was behavioral and emotional disorders
      with onset usually occurring in childhood and adolescence (RMB 8,828.4; US$
      1,419.4, as compared to the average reported household annual income of US$
      2,095.3 in China). The average annual growth rate of per capita hospitalization
      cost was 23.6%, with the inpatient cost reaching RMB 11,949 (US$ 1921.1) in 2012.
      The hospitalization cost was found to be strongly associated with hospital length
      of stay, level of care, age, employment status, admission diagnoses, and
      frequency of hospitalization. DISCUSSION: Our study found that mental health
      inpatient resources use, particularly hospitalization cost, has been growing at
      an increasing rate. In our sample, hospitalization cost nearly tripled from 2005
      to 2012. Mental illnesses and the related economic burden on the population will
      continue to grow, making mental health a major public health issue in China.
      Hospital length of stay was found to be increasing in our sample, and positively
      correlated with hospitalization cost. Childhood and adolescence behavioral and
      emotional disorders were found to be significantly associated with higher
      inpatient cost. IMPLICATIONS FOR HEALTH POLICIES AND FUTURE RESEARCH: The policy
      implications generated from the results of this study are two-fold: first of all,
      in order to meet the growing need of mental health care in China, the government
      needs to significantly increase its spending in preventing and treating mental
      illnesses. Second, cost containment in inpatient care would become a major
      challenge for mental health policy makers in China. Government support, clinical
      practices and guideline development, as well as research are urgently needed to
      promote mental health prevention and improve the efficiency of mental health
      system in China. The current mental health system, like the overall healthcare
      system in China, relies heavily on hospital inpatient care. In order to build a
      sustainable mental health care system to meet increasing population need in
      China, it is crucial to integrate mental health care reform with the ongoing
      primary health care reform. Future mental health policy reform and research in
      China should put more focus on how to strengthen primary care system as well as
      community support, establish effective two-tier referring mechanism between
      hospital and primary care system, and to ensure continuity of care.

PMID- 25599282
TI  - In vivo abdominal magnetic resonance elastography for the assessment of portal
      hypertension before and after transjugular intrahepatic portosystemic shunt
      implantation.
AB  - OBJECTIVE: The objective of this study was to investigate the correlation between
      hepatic venous pressure gradient (HVPG) and in vivo viscoelasticity of the liver
      and spleen before and after transjugular intrahepatic portosystemic shunt (TIPS)
      implantation. MATERIALS AND METHODS: Ten patients with portal hypertension were
      examined twice by 3-dimensional multifrequency magnetic resonance elastography as
      well as prior and subsequent TIPS intervention; HVPG was also measured during
      TIPS placement. Five harmonic vibrations (25-60 Hz) were transferred to the
      abdominal region and recorded for the reconstruction of 2 viscoelastic constants,
      |G*| and phi, corresponding to the magnitude and the phase angle of the complex
      shear modulus G* of the liver and spleen. RESULTS: All patients had cirrhosis,
      yielding high |G*| values in the liver (8.34 +/- 2.18 kPa) and spleen (8.44 +/-
      1.36 kPa). In both organs, a decrease of |G*| after TIPS placement was observed
      (liver: 8.34 +/- 2.18 kPa vs 7.02 +/- 1.46 kPa, P = 0.01; spleen: 8.44 +/- 1.36
      kPa vs 7.06 +/- 1.32 kPa, P = 0.01), whereas phi was insensitive to TIPS.
      Relative changes in |G*| of the spleen were correlated with the relative change
      of HVPG (R2 = 0.659, P = 0.013). CONCLUSIONS: The observed linear correlation
      between spleen viscoelasticity HVPG raises the prospect of an image-based
      noninvasive assessment of portal pressure by magnetic resonance elastography in
      the follow-up of TIPS placements.

PMID- 25599283
TI  - Commentary: The place of tenofovir disoproxil fumarate in pediatric
      antiretroviral therapy.

PMID- 25599284
TI  - Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected
      adolescents failing antiretroviral therapy: the final results of study GS-US-104
      0321.
AB  - BACKGROUND: Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in
      HIV-infected adolescents are limited. We present final results from the open
      label (OL) TDF extension following the randomized, placebo (PBO)-controlled,
      double-blind phase of GS-US-104-0321 (Study 321). METHODS: HIV-infected 12- to 17
      year-olds treated with TDF 300 mg or PBO with an optimized background regimen
      (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study
      extension. HIV-1 RNA and safety, including bone mineral density (BMD), was
      assessed in all TDF recipients. RESULTS: Eighty-one subjects received TDF (median
      duration 96 weeks). No subject died or discontinued OL TDF for
      safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were
      30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized
      to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to
      TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000
      c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At
      week 144, median decrease in estimated glomerular filtration rate was 38.1
      mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total
      body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21;
      +0.457 for spine, +0.152 for total body less head) were observed at week 144.
      Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline.
      CONCLUSIONS: Some subjects had virologic responses to TDF plus OBR, and TDF
      resistance was rare. TDF was well tolerated and can be considered for treatment
      of HIV-infected adolescents.

PMID- 25599286
TI  - Myelopathy is associated with increased all-cause morbidity and mortality
      following anterior cervical discectomy and fusion: a study of 5256 patients in
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP).
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate whether myelopathy is
      associated with increased morbidity and mortality after anterior cervical
      discectomy and fusion (ACDF) compared with other indications for this procedure.
      SUMMARY OF BACKGROUND DATA: ACDF is the most common surgical procedure for the
      management of a spectrum of cervical spine pathologies. As a more advanced
      condition, myelopathy is generally thought to be associated with higher morbidity
      and mortality after this procedure, but there is limited evidence to support this
      supposition. The current study compares outcomes of ACDF procedures performed for
      myelopathy with those performed for other indications, controlling for other
      patient factors. METHODS: Patients who underwent ACDF between 2010 and 2012 were
      identified in the American College of Surgeons National Surgical Quality
      Improvement Program database. Patients with myelopathy were identified by
      diagnosis codes for cervical myelopathy. Bivariate and multivariate logistic
      regressions were performed to compare 30-day adverse events and readmission
      between groups. Multivariate analyses controlled for patient and surgical
      characteristics. RESULTS: A total of 5256 ACDF procedures met inclusion criteria,
      of which 1425 (27.3%) were performed for cervical myelopathy. Patients with
      myelopathy were older and were less healthy than patients without myelopathy.
      Multivariate analysis controlling for baseline patient characteristics found that
      patients with myelopathy were at significantly increased risk of any adverse
      event (odds ratio = 1.5), any severe adverse event (odds ratio = 1.8), and death
      (odds ratio = 8.9) compared with patients without myelopathy. CONCLUSION: After
      adjusting for baseline patient characteristics, not only were any adverse events
      and serious adverse events more common after ACDF for patients with myelopathy
      than for patients without myelopathy, but mortality was approximately 9 times
      more likely. It is important for surgical planning and patient counseling to keep
      this significant difference in mind for this common procedure that has different
      morbidities based on the pathology for which it is performed. LEVEL OF EVIDENCE:
      3.

PMID- 25599285
TI  - Fluoroscopic assessment of lumbar total disc replacement kinematics during
      walking.
AB  - STUDY DESIGN: Descriptive. OBJECTIVE: The purpose of this study was to determine
      the in vivo kinematics of functional spinal units, during gait, in individuals
      with a single-level lumbar total disc replacement (TDR). SUMMARY OF BACKGROUND
      DATA: TDR is a motion preservation technology that offers an alternative to
      spinal fusion for treatment of degenerative disc disease. The aim of TDRs is to
      replicate motion of the functional spinal units, which may protect adjacent
      intervertebral discs against accelerated degeneration. At present, there is
      limited understanding of the in vivo motion of TDRs, particularly during dynamic
      activities such as gait. Such information is important for understanding the wear
      characteristics of TDRs and furthering design rationale of future implants.
      METHODS: TDR motions were obtained from 24 participants who underwent
      implantation with single-level L4-L5 or L5-S1 CHARITE or In Motion TDRs. Video
      fluoroscopy was used to obtain measurements in the frontal and sagittal planes
      during fixed speed treadmill walking. RESULTS: The mean range of motion between
      the upper and lower lumbar TDR endplates during walking was 1.6 degrees  and 2.4
      degrees  in the frontal and sagittal planes, respectively. These values were
      significantly different from zero and corresponded to 19% of the maximum static
      range of motion in each plane. CONCLUSION: Lumbar TDRs provide a degree of motion
      preservation at the operative level during moderate speed walking. The
      distribution of lumbar TDR motions during walking presented here will inform
      relevant standards for conducting standardized tests of lumbar TDRs, particularly
      wear assessments, and, hence, enable more realistic mechanical and computer-based
      wear simulations to be performed. LEVEL OF EVIDENCE: N/A.

PMID- 25599288
TI  - Obesity is associated with an increased rate of incidental durotomy in lumbar
      spine surgery.
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To determine the impact
      of obesity on the rate of incidental durotomy in lumbar spine surgery. SUMMARY OF
      BACKGROUND DATA: There is a paucity of data on the overall impact of obesity on
      the rate of incidental durotomy in lumbar spine surgery, specifically with regard
      to the type of procedure performed. METHODS: A large administrative database was
      queried for all patients who underwent lumbar spine surgery for decompression
      and/or fusion. They were then stratified into separate cohorts on the basis of
      body mass index and by procedural codes. Documentation of incidental durotomy was
      noted. Patient demographics and associated comorbidities were assessed. Odds
      ratios and 95% confidence intervals were calculated and chi test was used to
      assess for statistical significance. RESULTS: The incidental durotomy ranged from
      0.5% to 2.6%, with the highest rates observed in multilevel laminectomies and
      revision decompressions in the obese and morbidly obese groups. For patients who
      underwent decompression only procedures, nonobese patients had a significantly
      lower rate of durotomy than the obese and morbidly obese cohorts. For patients
      who underwent fusion with or without decompression, there was a significantly
      increased rate of durotomy in obese patients compared with nonobese patients. The
      morbidly obese cohort also had significantly higher rates of incidental durotomy
      than the nonobese cohort in both revision decompression and revision fusion
      procedures. CONCLUSION: This analysis of a large administrative database
      demonstrates that obesity is associated with increased rates of incidental
      durotomy in lumbar spine surgery. Furthermore, obesity, in association with
      increasing complexity of the procedure, increases the rate of incidental durotomy
      in lumbar spine surgery. Surgeons must be aware of these increased risks as the
      rate of obesity increases in the population. LEVEL OF EVIDENCE: 3.

PMID- 25599287
TI  - Implementing stratified primary care management for low back pain: cost-utility
      analysis alongside a prospective, population-based, sequential comparison study.
AB  - STUDY DESIGN: Within-study cost-utility analysis. OBJECTIVE: To explore the cost
      utility of implementing stratified care for low back pain (LBP) in general
      practice, compared with usual care, within risk-defined patient subgroups (that
      is, patients at low, medium, and high risk of persistent disabling pain). SUMMARY
      OF BACKGROUND DATA: Individual-level data collected alongside a prospective,
      sequential comparison of separate patient cohorts with 6-month follow-up.
      METHODS: Adopting a cost-utility framework, the base case analysis estimated the
      incremental LBP-related health care cost per additional quality-adjusted life
      year (QALY) by risk subgroup. QALYs were constructed from responses to the 3
      level EQ-5D, a preference-based health-related quality of life instrument.
      Uncertainty was explored with cost-utility planes and acceptability curves.
      Sensitivity analyses examined alternative methodological approaches, including a
      complete case analysis, the incorporation of non-back pain-related health care
      use and estimation of societal costs relating to work absence. RESULTS:
      Stratified care was a dominant treatment strategy compared with usual care for
      patients at high risk, with mean health care cost savings of L124 and an
      incremental QALY estimate of 0.023. The likelihood that stratified care provides
      a cost-effective use of resources for patients at low and medium risk is no
      greater than 60% irrespective of a decision makers' willingness-to-pay for
      additional QALYs. Patients at medium and high risk of persistent disability in
      paid employment at 6-month follow-up reported, on average, 6 fewer days of LBP
      related work absence in the stratified care cohort compared with usual care
      (associated societal cost savings per employed patient of L736 and L652,
      respectively). CONCLUSION: At the observed level of adherence to screening tool
      recommendations for matched treatments, stratified care for LBP is cost-effective
      for patients at high risk of persistent disabling LBP only. LEVEL OF EVIDENCE: 2.

PMID- 25599290
TI  - Accuracy of fluoroscopy versus computer-assisted navigation for the placement of
      anterior cervical pedicle screws.
AB  - STUDY DESIGN: Randomized laboratory cadaver study. OBJECTIVE: The objective of
      this study was to determine the accuracy of anterior transpedicular screw
      placement in the cervical spine using conventional fluoroscopy versus computer
      assisted navigation. SUMMARY OF BACKGROUND DATA: Traditionally, global cervical
      instability has required anterior and posterior fixation due to the superior
      biomechanical stability of circumferential constructs. Anterior transpedicular
      screws (ATPS) have recently been advocated as a single surgical approach. Current
      clinical publications report using fluoroscopic guidance for screw placement.
      Computer-assisted navigation (CAN) systems have demonstrated enhanced accuracy of
      pedicle screw placement at all spine levels but have not been assessed for ATPS.
      METHODS: The anterior vertebrae of 9 fresh frozen cadaver cervical spines were
      exposed, preserving the lateral and posterior soft tissue envelope. Nine
      practicing spine surgeons placed 2.0-mm titanium anterior transpecidular
      Kirschner wires into the C3-T1 pedicles bilaterally using fluoroscopy or CAN
      guidance. Specimens were imaged by computed tomography and virtual screws were
      overlaid on the K-wires. Targeting accuracy was compared between the 2 techniques
      in all planes using a 5-level grading scale. RESULTS: The percentage of
      acceptable screw placements for fluoroscopy and CAN was 42.6% and 66.7%,
      respectively (P = 0.012). Catastrophic screw placement (grade 3 or 4) was 33.3%
      for fluoroscopy and 16.7% for CAN. In the multivariable model, the accuracy rate
      was 67% lower for fluoroscopy than for CAN after controlling for other factors
      (odds ratio: 0.33, 95% confidence interval: 0.14-0.79). CONCLUSION: The accuracy
      of CAN-guided placement of K-wires for ATPS was superior to placement under
      fluoroscopic guidance, demonstrating statistically more acceptable screw
      placements and significantly less catastrophic virtual screws. However,
      malposition was still high, with potential for vertebral artery and neurological
      injury in a clinical setting. Further advancement in current ATPS techniques is
      warranted prior to widespread implementation in a patient setting. LEVEL OF
      EVIDENCE: N/A.

PMID- 25599291
TI  - Penile cancer: organ-sparing surgery.
AB  - PURPOSE OF REVIEW: Penile cancer is a devastating disease, usually diagnosed
      late, that requires wide excisions, which causes alterations in self-esteem and
      body image, affecting sexual and urinary functions, which compromise quality of
      life. Recently, an increasing interest in penile-sparing surgeries (PSSs) has
      emerged, aiming to spare patients from these complications. RECENT FINDINGS:
      Several options of PSS have been popularized for selected cases (Ta-1, Tis and
      some T2), such as wide local excision, circumcision, partial penectomy, total or
      partial glansectomies with or without glans-resurfacing procedures, as well as
      new glans reconstructions using spatulated urethral advances or free skin grafts.
      These options, in general, achieve good local control, with adequate functional
      results and satisfactory cosmetic appearance. The local recurrences, however, are
      slightly higher than amputations. Contemporary techniques such as laser or
      cryotherapy can be performed in selected cases. SUMMARY: PSS must be indicated
      only for superficial penile cancer cases, such as Tis and Ta-1, and for selected
      invasive lesions (small distal pT2 tumors). Candidates for PSS should be adherent
      to follow-up requirements, allowing early detection of local recurrences. Prompt
      and effective salvage procedures are mandatory in these situations.

PMID- 25599289
TI  - Long-term radiographic outcomes of a central hook-rod construct for osteotomy
      closure: minimum 5-year follow-up.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate long-term effectiveness
      of central hook-rod constructs for posterior spinal osteotomy closure. SUMMARY OF
      BACKGROUND DATA: During osteotomy site closure various techniques are used,
      including patient positioning, rod cantilevering, extending fixation points, and
      compressing through pedicle fixation points. All add premature stress on fixation
      points and may lead to loosening/eventual fixation failure. To avoid this, we
      often use a central compression hook-rod construct for osteotomy closure.
      METHODS: Fifty-six consecutive patients with fixed sagittal imbalance were
      treated with multilevel posterior column osteotomies (N = 19), pedicle
      subtraction osteotomy (N = 31), or vertebral column resection (N = 6). All 56
      patients had undergone osteotomy closure using central compression hook-rod
      constructs and were analyzed at a follow-up of 5 years or more. Compression hooks
      were inserted into the fusion mass or lamina above/below the osteotomy and
      centrally attached to a short rod connected to pedicle screw-based rods via a
      cross-link. Diagnoses included sagittal imbalance associated with scoliosis (N =
      39), degenerative sagittal imbalance (N = 14), ankylosing spondylitis (N = 2),
      and Scheuermann's kyphosis (N = 1). There were 55 revision cases and 1 primary.
      Radiographic/clinical analysis was performed to evaluate the
      efficacy/complications of this technique. RESULTS: Overall lumbar lordosis
      increased an average of 31.7 degrees  and local lordosis through the osteotomy
      site increased an average of 29.3 degrees . Sagittal balance improved by an
      average of 92 mm. In all cases, osteotomy closures were performed without screw
      loosening or loss of correction intraoperatively. At a follow-up of 5 years or
      more, no failures of the hook-rod construct were seen, but there were 3 patients
      with partial implant failure; however, no symptomatic pseudarthroses at the
      osteotomy sites occurred. Seven patients developed pseudarthrosis below the
      central hook-rod construct. CONCLUSION: A central hook-rod construct is safe,
      controlled, and effective for applying compressive forces to close various spinal
      osteotomies without fixation failure or pseudarthrosis at the osteotomy site
      noted at a follow-up of 5 or more years. It adds fixation strength to the overall
      construct avoiding undue stress on pedicle screws. LEVEL OF EVIDENCE: 3.

PMID- 25599292
TI  - PAIN(r): our "new look".

PMID- 25599293
TI  - Meet PAIN pictured.

PMID- 25599294
TI  - Quantitative sensory testing in predicting persistent pain after joint
      replacement surgery: promise and challenges.

PMID- 25599295
TI  - Molecular players of tumor-nerve interactions.

PMID- 25599296
TI  - Postoperative pain treatment after total hip arthroplasty: a systematic review.
AB  - Treatment of postoperative pain should rely on results from randomized controlled
      trials and meta-analyses of high scientific quality. The efficacy of a particular
      intervention may depend on the type of surgical procedure, which supports the
      reporting of "procedure-specific" interventions. The aim of this systematic
      review was to document the procedure-specific evidence for analgesic
      interventions after total hip arthroplasty (THA). This PRISMA-compliant and
      PROSPERO-registered review includes randomized placebo-controlled trials (RCTs)
      of medication-based analgesic interventions after THA. Endpoints were
      postoperative opioid consumption, pain scores (rest and during mobilization),
      adverse events, and length of hospital stay. Fifty-eight trials with 19 different
      interventions were retrieved. High risk of bias, substantial differences in
      assessment-tools and criteria for pain, irregular reporting of adverse events,
      considerable differences in supplemental analgesic consumption, and basic
      analgesic regimens generally characterized trials. Meta-analyses of non-steroidal
      anti-inflammatory drugs, local infiltration analgesia, intrathecal opioids, and
      lumbar plexus block provided a 24-hour intravenous morphine-sparing effect of
      14.1 (95 % confidence interval: 8.0-20.2) mg, 7.5 (3.7-11.3) mg, 19.8 (14.9-24.7)
      mg, and 11.9 (6.4-17.3) mg, respectively. Non-steroidal anti-inflammatory drugs
      and lumbar plexus block were demonstrated to provide reductions in postoperative
      pain scores. Intrathecal opioids increased pruritus, and lumbar plexus block
      reduced nausea and pruritus. The GRADE-rated quality of evidence ranged from low
      to very low throughout the analyses. This review demonstrated, that some
      analgesic interventions may have the capacity to reduce mean opioid requirements
      and/or mean pain intensity compared with controls, but the available randomized
      placebo-controlled trials does not allow a designation of a "best proven
      intervention" for THA. 

PMID- 25599297
TI  - Remembering the pain of childhood: applying a developmental perspective to the
      study of pain memories.

PMID- 25599298
TI  - Beyond nociception: the imprecision hypothesis of chronic pain.

PMID- 25599299
TI  - Opposite effects of the same drug: reversal of topical analgesia by nocebo
      information.
AB  - Several studies have shown that psychological factors such as learning,
      expectation, and emotions can affect pharmacological treatment and shape both
      favorable and adverse effects of drugs. This study investigated whether nocebo
      information provided during administration of an analgesic cream could reverse
      topical analgesia to hyperalgesia. Furthermore, we tested whether nocebo effects
      were mediated by negative emotional activation. A total of 142 healthy volunteers
      (73 women) were randomized into 6 groups. A topical analgesic cream (Emla) was
      administered together with suggestions of analgesia in 1 group, whereas another
      group received Emla with suggestions of hyperalgesia. Two other groups received a
      placebo cream together with the same information as the groups receiving Emla. A
      fifth group received Emla with no specific information about the effect, and the
      sixth group received no treatment but the same pain induction as the other
      groups. Heat pain stimulation (48 degrees C) was administered during a pretest
      and 2 posttests. Pain was continuously recorded during stimulation, and measures
      of subjective stress and blood pressure were obtained before the pretest, after
      the application of cream, and after the posttests. The results revealed that pain
      was significantly lower in the group receiving Emla with positive information and
      highest in the groups receiving suggestions of hyperalgesia, regardless of
      whether Emla or the placebo was administered. Mediation analyses showed that
      stress and blood pressure mediated hyperalgesia after nocebo suggestions. These
      results suggest that nocebo information can reverse topical analgesia and that
      emotional factors can explain a significant proportion of variance in nocebo
      hyperalgesia. 

PMID- 25599301
TI  - Presurgical assessment of temporal summation of pain predicts the development of
      chronic postoperative pain 12 months after total knee replacement.
AB  - Patients with knee osteoarthritis demonstrate decreased pressure pain thresholds
      (PPTs), facilitated temporal summation (TS) of pain, and decreased conditioned
      pain modulation (CPM) compared with healthy controls. This study aimed to
      correlate preoperative PPTs, TS, and CPM with the development of chronic
      postoperative pain after total knee replacement (TKR) surgery. Knee pain
      intensity (visual analog scale [VAS]: 0-10), PPTs, TS, and CPM were collected
      before, 2 months, and 12 months after TKR. Patients were divided into a low-pain
      (VAS < 3) and a high-pain (VAS >= 3) group based on their VAS 12 months after
      TKR. The high-pain group (N = 17) had higher pain intensities compared with the
      low-pain group (N = 61) before surgery (P = 0.009) and 12 months after surgery (P
      < 0.001). The PPTs of the low-pain groups were normalized for all measurement
      sites comparing presurgery with 12 months postsurgery (P < 0.05, contralateral
      arm: P = 0.059), which was not the case for the high-pain group. The low-pain
      group showed a functional inhibitory CPM preoperatively and 12 months
      postoperatively (P < 0.05), which was not found in the high-pain group. The high
      pain group had higher facilitated TS preoperatively and 12 months postoperatively
      compared with the low-pain group (P < 0.05). Preoperative TS level correlated to
      12-month postoperative VAS (R = 0.240, P = 0.037). Patients who developed
      moderate-to-severe pain had pronociceptive changes compared with patients who
      developed mild pain postsurgery. Preoperative TS level correlated with the
      postoperative pain intensity and may be a preoperative mechanistic predictor for
      the development of chronic postoperative pain in patients with osteoarthritis
      after TKR.

PMID- 25599300
TI  - Preoperative widespread pain sensitization and chronic pain after hip and knee
      replacement: a cohort analysis.
AB  - Chronic pain after joint replacement is common, affecting approximately 10% of
      patients after total hip replacement (THR) and 20% of patients after total knee
      replacement (TKR). Heightened generalized sensitivity to nociceptive input could
      be a risk factor for the development of this pain. The primary aim of this study
      was to investigate whether preoperative widespread pain sensitivity was
      associated with chronic pain after joint replacement. Data were analyzed from 254
      patients receiving THR and 239 patients receiving TKR. Pain was assessed
      preoperatively and at 12 months after surgery using the Western Ontario and
      McMaster Universities Osteoarthritis Pain Scale. Preoperative widespread pain
      sensitivity was assessed through measurement of pressure pain thresholds (PPTs)
      at the forearm using an algometer. Statistical analysis was conducted using
      linear regression and linear mixed models, and adjustments were made for
      confounding variables. In both the THR and TKR cohort, lower PPTs (heightened
      widespread pain sensitivity) were significantly associated with higher
      preoperative pain severity. Lower PPTs were also significantly associated with
      higher pain severity at 12 months after surgery in the THR cohort. However, PPTs
      were not associated with the change in pain severity from preoperative to 12
      months postoperative in either the TKR or THR cohort. These findings suggest that
      although preoperative widespread pressure pain sensitivity is associated with
      pain severity before and after joint replacement, it is not a predictor of the
      amount of pain relief that patients gain from joint replacement surgery,
      independent of preoperative pain severity. 

PMID- 25599302
TI  - Transcranial direct current stimulation as a treatment for patients with
      fibromyalgia: a randomized controlled trial.
AB  - Previous studies suggest that transcranial direct current stimulation (tDCS) over
      the primary motor cortex (M1) reduces chronic pain levels. In this randomized
      controlled trial, we investigated the effects of 5 consecutive 20-minute sessions
      of 2-mA anodal tDCS directed to the M1 in 48 patients (45 females) with
      fibromyalgia. Changes in pain, stress, daily functioning, psychiatric symptoms,
      and health-related quality of life were measured. Pain and stress were measured
      30 days before treatment, at each treatment, and 30 days after treatment by using
      short message service on mobile phones. Patients were randomized to the active or
      sham tDCS group by receiving individual treatment codes associated either with
      the sham or active tDCS in the stimulator. Adverse effects were registered using
      a standardized form. A small but significant improvement in pain was observed
      under the active tDCS condition but not under the sham condition. Fibromyalgia
      related daily functioning improved in the active tDCS group compared with the
      sham group. The stimulation was well tolerated by the patients, and no
      significant difference in the adverse effects between the groups was observed.
      The results suggest that tDCS has the potential to induce statistically
      significant pain relief in patients with fibromyalgia, with no serious adverse
      effects, but small effect sizes indicate that the results are unlikely to reflect
      clinically important changes. 

PMID- 25599304
TI  - Failure of intrathecal ketorolac to reduce remifentanil-induced postinfusion
      hyperalgesia in humans.
AB  - In rodents, acute exposure to opioids results in transient antinociception
      followed by longer lasting hypersensitivity to tactile or thermal stimuli, a
      phenomenon termed opioid-induced hyperalgesia. This hypersensitivity can be
      blocked or reversed by intrathecally administered cyclooxygenase inhibitors,
      including ketorolac, suggesting a role for spinal prostaglandins. In surgical
      patients, the dose of intraoperative opioid, particularly the short-acting drug,
      remifentanil, is directly related to increased pain and opioid requirements for
      many hours postoperatively. In addition, experimentally induced tactile
      hypersensitivity in humans is exaggerated after cessation of remifentanil
      infusions. The degree of this experimental opioid-induced hyperalgesia is reduced
      by systemic treatment with cyclooxygenase inhibitors, and investigators have
      speculated that this reduction reflects the actions in the central nervous
      system, most likely in the spinal cord. To test this hypothesis, we measured
      cerebrospinal fluid prostaglandin E2 concentrations during and after remifentanil
      infusion in 30 volunteers. These volunteers received intrathecal ketorolac or
      saline in a random, blinded manner during intravenous remifentanil infusion after
      generation of hypersensitivity by topical capsaicin. Remifentanil reduced pain to
      noxious heat stimuli and reduced areas of capsaicin-induced hypersensitivity
      similarly in those receiving intrathecal ketorolac or saline. The primary outcome
      measure, area of capsaicin-induced hypersensitivity after stopping remifentanil,
      showed a similar increase in those receiving ketorolac as in those receiving
      saline. Cerebrospinal fluid prostaglandin E2 concentrations did not increase
      during postinfusion hyperalgesia compared with those during infusion, and they
      were not increased during infusion compared with those in historical controls.
      These data fail to support the hypothesis that acute opioid-induced hyperalgesia
      reflects spinal cyclooxygenase activation causing central sensitization. 

PMID- 25599303
TI  - Results availability for analgesic device, complex regional pain syndrome, and
      post-stroke pain trials: comparing the RReADS, RReACT, and RReMiT databases.
AB  - Evidence-based medicine rests on the assumption that treatment recommendations
      are robust, free from bias, and include results of all randomized clinical
      trials. The Repository of Registered Analgesic Clinical Trials search and
      analysis methodology was applied to create databases of complex regional pain
      syndrome (CRPS) and central post-stroke pain (CPSP) trials and adapted to create
      the Repository of Registered Analgesic Device Studies databases for trials of
      spinal cord stimulation (SCS), repetitive transcranial magnetic stimulation
      (rTMS), and transcranial direct current stimulation (tDCS). We identified 34 CRPS
      trials, 18 CPSP trials, 72 trials of SCS, and 92 trials of rTMS/tDCS.
      Irrespective of time since study completion, 45% of eligible CRPS and CPSP trials
      and 46% of eligible SCS and rTMS/tDCS trials had available results (peer-reviewed
      literature, results entered on registry, or gray literature); peer-reviewed
      publications could be found for 38% and 39%, respectively. Examining almost 1000
      trials across a spectrum of painful disorders (fibromyalgia, diabetic painful
      neuropathy, post-herpetic neuralgia, migraine, CRPS, CPSP) and types of
      treatment, no single study characteristic consistently predicts unavailability of
      results. Results availability is higher 12 months after study completion but
      remains below 60% for peer-reviewed publications. Recommendations to increase
      results availability include supporting organizations advocating for
      transparency, enforcing existing results reporting regulations, enabling all
      primary registries to post results, stating trial registration numbers in all
      publication abstracts, and reducing barriers to publishing "negative" trials. For
      all diseases and treatment modalities, evidence-based medicine must rigorously
      adjust for the sheer magnitude of missing results in formulating treatment
      recommendations. 

PMID- 25599305
TI  - Intrathecal clonidine and adenosine: effects on pain and sensory processing in
      patients with chronic regional pain syndrome.
AB  - Chronic pain may be accompanied by hyperalgesia and allodynia, and analgesic
      interventions may reduce these hypersensitivity phenomena. Preclinical data
      suggest that intrathecal clonidine and adenosine reduce hypersensitivity, but
      only clonidine reduces pain; therefore, we tested the effects of these
      interventions in patients with chronic pain. Twenty-two subjects with pain and
      hyperalgesia in a lower extremity from complex regional pain syndrome were
      recruited in a double-blind crossover study to receive intrathecal clonidine, 100
      MUg, or adenosine, 2 mg. Primary outcome measure was proportion with >=30%
      reduction in pain 2 hours after injection, and secondary measures were pain
      report, areas of hypersensitivity, and temporal summation to heat stimuli.
      Treatments did not differ in the primary outcome measure (10 met success
      criterion after clonidine administration and 5 after adenosine administration),
      although they did differ in pain scores over time, with clonidine having a 3-fold
      greater effect (P = 0.014). Both drugs similarly reduced areas of hyperalgesia
      and allodynia by approximately 30% and also inhibited temporal summation. The
      percentage change in pain report did not correlate with the percentage change in
      areas of hyperalgesia (P = 0.09, r = 0.08) or allodynia (P = 0.24, r = 0.24)
      after drug treatment. Both intrathecal clonidine and adenosine acutely inhibit
      experimentally induced and clinical hypersensitivity in patients with chronic
      regional pain syndrome. Although these drugs do not differ in analgesia by the
      primary outcome measure, their difference in effect on pain scores over time and
      lack of correlation between effect on pain and hypersensitivity suggest that
      analgesia does not parallel antihyperalgesia with these treatments. 

PMID- 25599306
TI  - Identifying specific profiles in patients with different degrees of painful knee
      osteoarthritis based on serological biochemical and mechanistic pain biomarkers:
      a diagnostic approach based on cluster analysis.
AB  - Biochemical and pain biomarkers can be applied to patients with painful
      osteoarthritis profiles and may provide more details compared with conventional
      clinical tools. The aim of this study was to identify an optimal combination of
      biochemical and pain biomarkers for classification of patients with different
      degrees of knee pain and joint damage. Such profiling may provide new diagnostic
      and therapeutic options. A total of 216 patients with different degrees of knee
      pain (maximal pain during the last 24 hours rated on a visual analog scale [VAS])
      (VAS 0-100) and 64 controls (VAS 0-9) were recruited. Patients were separated
      into 3 groups: VAS 10 to 39 (N = 81), VAS 40 to 69 (N = 70), and VAS 70 to 100 (N
      = 65). Pressure pain thresholds, temporal summation to pressure stimuli, and
      conditioning pain modulation were measured from the peripatellar and
      extrasegmental sites. Biochemical markers indicative for autoinflammation and
      immunity (VICM, CRP, and CRPM), synovial inflammation (CIIIM), cartilage loss
      (CIIM), and bone degradation (CIM) were analyzed. WOMAC, Lequesne, and pain
      catastrophizing scores were collected. Principal component analysis was applied
      to select the optimal variable subset, and cluster analysis was applied to this
      subset to create distinctly different knee pain profiles. Four distinct knee pain
      profiles were identified: profile A (N = 27), profile B (N = 59), profile C (N =
      85), and profile D (N = 41). Each knee pain profile had a unique combination of
      biochemical markers, pain biomarkers, physical impairments, and psychological
      factors that may provide the basis for mechanism-based diagnosis, individualized
      treatment, and selection of patients for clinical trials evaluating analgesic
      compounds. These results introduce a new profiling for knee OA and should be
      regarded as preliminary. 

PMID- 25599307
TI  - Differences in pain-related fear acquisition and generalization: an experimental
      study comparing patients with fibromyalgia and healthy controls.
AB  - Anomalies in fear learning, such as failure to inhibit fear to safe stimuli, lead
      to sustained anxiety, which in turn may augment pain. In the same vein, stimulus
      generalization is adaptive as it enables individuals to extrapolate the
      predictive value of 1 stimulus to similar stimuli. However, when fear spreads in
      an unbridled way to novel technically safe stimuli, stimulus generalization
      becomes maladaptive and may lead to dysfunctional avoidance behaviors and
      culminate in severe pain disability. In a voluntary movement conditioning
      paradigm, we compared the acquisition and generalization of pain-related fear in
      patients with fibromyalgia (FM) and healthy controls. During acquisition,
      participants received predictable pain in 1 context (ie, 1 movement predicts
      pain, whereas another does not), and unpredictable pain in another (ie, pain
      never contingent upon movement). Fear generalization to novel movements
      (resembling the original painful or nonpainful movement) was tested in both
      contexts. Results indicated that the FM group showed slower differential
      acquisition of pain-related fear in the predictable context, and more contextual
      pain-related fear in the unpredictable context. Fear of movement-related pain
      spreads selectively to novel movements similar to the original painful movement,
      and not to those resembling the nonpainful movement in the healthy controls, but
      nondifferential fear generalization was observed in FM. As expected, in the
      unpredictable context, we also observed nondifferential fear generalization; this
      effect was more pronounced in FM. Given the status of overgeneralization as a
      plausible transdiagnostic pathogenic marker, we believe that this research might
      increase our knowledge about pathogenesis of musculoskeletal widespread pain. 

PMID- 25599308
TI  - Caregivers' attentional bias to pain: does it affect caregiver accuracy in
      detecting patient pain behaviors?
AB  - Attentional bias to pain among family caregivers of patients with pain may
      enhance the detection of pain behaviors in patients. However, both relatively
      high and low levels of attentional bias may increase disagreement between
      patients and caregivers in reporting pain behaviors. This study aims to provide
      further evidence for the presence of attentional bias to pain among family
      caregivers, to examine the association between caregivers' attentional bias to
      pain and detecting pain behaviors, and test whether caregivers' attentional bias
      to pain is curvilinearly related to patient and caregiver disagreement in
      reporting pain behaviors. The sample consisted of 96 caregivers, 94 patients with
      chronic pain, and 42 control participants. Caregivers and controls completed a
      dot-probe task assessing attention to painful and happy stimuli. Both patients
      and caregivers completed a checklist assessing patients' pain behavior. Although
      caregivers did not respond faster to pain congruent than pain incongruent trials,
      caregiver responses were slower in pain incongruent trials compared with happy
      incongruent trials. Caregivers showed more bias toward pain faces than happy
      faces, whereas control participants showed more bias toward happy faces than pain
      faces. Importantly, caregivers' attentional bias to pain was significantly
      positively associated with reporting pain behaviors in patients above and beyond
      pain severity. It is reassuring that attentional bias to pain was not related to
      disagreement between patients and caregivers in reporting pain behaviors. In
      other words, attentional bias does not seem to cause overestimation of pain
      signals. 

PMID- 25599309
TI  - Supervised walking in comparison with fitness training for chronic back pain in
      physiotherapy: results of the SWIFT single-blinded randomized controlled trial
      (ISRCTN17592092).
AB  - Effectiveness of brief/minimal contact self-activation interventions that
      encourage participation in physical activity (PA) for chronic low back pain (CLBP
      >12 weeks) is unproven. The primary objective of this assessor-blinded randomized
      controlled trial was to investigate the difference between an individualized
      walking programme (WP), group exercise class (EC), and usual physiotherapy (UP,
      control) in mean change in functional disability at 6 months. A sample of 246
      participants with CLBP aged 18 to 65 years (79 men and 167 women; mean age +/-
      SD: 45.4 +/- 11.4 years) were recruited from 5 outpatient physiotherapy
      departments in Dublin, Ireland. Consenting participants completed self-report
      measures of functional disability, pain, quality of life, psychosocial beliefs,
      and PA were randomly allocated to the WP (n = 82), EC (n = 83), or UP (n = 81)
      and followed up at 3 (81%; n = 200), 6 (80.1%; n = 197), and 12 months (76.4%; n
      = 188). Cost diaries were completed at all follow-ups. An intention-to-treat
      analysis using a mixed between-within repeated-measures analysis of covariance
      found significant improvements over time on the Oswestry Disability Index
      (Primary Outcome), the Numerical Rating Scale, Fear Avoidance-PA scale, and the
      EuroQol EQ-5D-3L Weighted Health Index (P < 0.05), but no significant between
      group differences and small between-group effect sizes (WP: mean difference at 6
      months, 6.89 Oswestry Disability Index points, 95% confidence interval [CI] -3.64
      to -10.15; EC: -5.91, CI: -2.68 to -9.15; UP: -5.09, CI: -1.93 to -8.24). The WP
      had the lowest mean costs and the highest level of adherence. Supervised walking
      provides an effective alternative to current forms of CLBP management. 

PMID- 25599310
TI  - Biopsychosocial influence on shoulder pain: risk subgroups translated across
      preclinical and clinical prospective cohorts.
AB  - Tailored treatment based on individual risk factors is an area with promise to
      improve options for pain relief. Musculoskeletal pain has a biopsychosocial
      nature, and multiple factors should be considered when determining risk for
      chronic pain. This study investigated whether subgroups comprised genetic and
      psychological factors predicted outcomes in preclinical and clinical models of
      shoulder pain. Classification and regression tree analysis was performed for an
      exercise-induced shoulder injury cohort (n = 190) to identify high-risk
      subgroups, and a surgical pain cohort (n = 150) was used for risk validation.
      Questionnaires for fear of pain and pain catastrophizing were administered before
      injury and preoperatively. DNA collected from saliva was genotyped for a priori
      selected genes involved with pain modulation (COMT and AVPR1A) and inflammation
      (IL1B and TNF/LTA). Recovery was operationalized as a brief pain inventory rating
      of 0/10 for current pain intensity and <2/10 for worst pain intensity. Follow-up
      for the preclinical cohort was in daily increments, whereas follow-up for the
      clinical cohort was at 3, 6, and 12 months postoperatively. Risk subgroups
      comprised the COMT high pain sensitivity variant and either pain catastrophizing
      or fear of pain were predictive of heightened shoulder pain responses in the
      preclinical model. Further analysis in the clinical model identified the COMT
      high pain sensitivity variant and pain catastrophizing subgroup as the better
      predictor. Future studies will determine whether these findings can be replicated
      in other anatomical regions and whether personalized medicine strategies can be
      developed for this risk subgroup. 

PMID- 25599311
TI  - Orthopedic surgery and bone fracture pain are both significantly attenuated by
      sustained blockade of nerve growth factor.
AB  - The number of patients suffering from postoperative pain due to orthopedic
      surgery and bone fracture is projected to dramatically increase because the human
      life span, weight, and involvement in high-activity sports continue to rise
      worldwide. Joint replacement or bone fracture frequently results in skeletal pain
      that needs to be adequately controlled for the patient to fully participate in
      needed physical rehabilitation. Currently, the 2 major therapies used to control
      skeletal pain are nonsteroidal anti-inflammatory drugs and opiates, both of which
      have significant unwanted side effects. To assess the efficacy of novel
      therapies, mouse models of orthopedic and fracture pain were developed and
      evaluated here. These models, orthopedic surgery pain and bone fracture pain,
      resulted in skeletal pain-related behaviors that lasted 3 weeks and 8 to 10
      weeks, respectively. These skeletal pain behaviors included spontaneous and
      palpation-induced nocifensive behaviors, dynamic weight bearing, limb use, and
      voluntary mechanical loading of the injured hind limb. Administration of anti
      nerve growth factor before orthopedic surgery or after bone fracture attenuated
      skeletal pain behaviors by 40% to 70% depending on the end point being assessed.
      These data suggest that nerve growth factor is involved in driving pain due to
      orthopedic surgery or bone fracture. These animal models may be useful in
      developing an understanding of the mechanisms that drive postoperative orthopedic
      and bone fracture pain and the development of novel therapies to treat these
      skeletal pains. 

PMID- 25599314
TI  - Impact of parent-directed education on parental use of pain treatments during
      routine infant vaccinations: a cluster randomized trial.
AB  - Educating parents about ways to minimize pain during routine infant vaccine
      injections at the point of care may positively impact on pain management
      practices. The objective of this cluster randomized trial was to determine the
      impact of educating parents about pain in outpatient pediatric clinics on their
      use of pain treatments during routine infant vaccinations. Four hospital-based
      pediatric clinics were randomized to intervention or control groups. Parents of 2
      to 4-month-old infants attending the intervention clinics reviewed a pamphlet
      and a video about vaccination pain management on the day of vaccination, whereas
      those in the control clinics did not. Parent use of specific pain treatments
      (breastfeeding, sugar water, topical anesthetics, and/or holding of infants) on
      the education day and at subsequent routine vaccinations 2 months later was the
      primary outcome. Altogether, 160 parent-infant dyads (80 per group) participated
      between November 2012 and February 2014; follow-up data were available for 126
      (79%). Demographics did not differ between groups (P > 0.05). On the education
      day and at follow-up vaccinations, use of pain interventions during vaccinations
      was higher in the intervention group (80% vs 26% and 68% vs 32%, respectively; P
      < 0.001 for both analyses). Educating parents about pain management in a hospital
      outpatient setting leads to higher use of pain interventions during routine
      infant vaccinations. 

PMID- 25599312
TI  - Somatosensory phenotype is associated with thalamic metabolites and pain
      intensity after spinal cord injury.
AB  - Neuropathic pain is one of the most difficult consequences of spinal cord injury
      (SCI). The clinical correlates of the underlying mechanisms responsible for
      neuropathic pain are not well understood, although methods such as quantitative
      somatosensory testing (QST) or brain imaging have been used to further a
      mechanism-based understanding of pain. Our previous SCI study demonstrated a
      significantly lower glutamate-glutamine/myo-inositol ratio (Glx/Ins) in the
      anterior cingulate cortex in persons with severe neuropathic pain compared with
      those with less severe neuropathic pain or pain-free, able-bodied controls,
      suggesting that a combination of decreased glutamatergic metabolism and glial
      activation may contribute to the development of severe neuropathic pain after
      SCI. The present study aimed to determine the relationships between somatosensory
      function below the level of injury and low thalamic Glx/Ins in persons with
      intense neuropathic pain after SCI. Participants underwent QST and a 3 Tesla
      proton magnetic resonance spectroscopy. A cluster analysis including SCI
      participants resulted in 1 group (n = 19) with significantly (P < 0.001) greater
      pain intensity (6.43 +/- 1.63; high neuropathic pain [HNP], and lower Glx/Ins
      [1.22 +/- 0.16]) and another group (n = 35) with lower pain intensity ratings
      (1.59 +/- 1.52, low neuropathic pain [LNP], and higher Glx/Ins [1.47 +/- 0.26]).
      After correcting for age, QST indicated significantly greater somatosensory
      function in the HNP group compared with the LNP group. Our results are consistent
      with research suggesting that damage to, but not abolition of, the spinothalamic
      tract contributes to development of neuropathic pain after SCI and that secondary
      inflammatory processes may amplify residual spinothalamic tract signals by
      facilitation, disinhibition, or sensitization. 

PMID- 25599315
TI  - Pain modulation efficiency delays seeking medical help in patients with acute
      myocardial infarction.
AB  - Rapid reperfusion is crucial to reduce mortality in patients with ST elevation
      myocardial infarction. Prehospital patient delay, defined as time from symptoms
      onset to the decision to seek medical attention, accounts for a large proportion
      of cases with delayed reperfusion. However, whether pain modulation processes are
      involved in this phenomenon is not known. We hypothesized that prehospital
      patient delay may be affected by a reduction of perceived pain perception and
      pain modulation pattern. Pain threshold, magnitude estimation of suprathreshold
      stimulation, mechanical temporal summation and conditioned pain modulation (CPM),
      and recalls of pain magnitude at the onset of chest pain were obtained in 67
      patients with first ST elevation myocardial infarction. The study's primary
      outcome was prehospital patient delay. The median patient delay was 24
      (interquartile range, 0.5-72) hours. Of all psychophysical pain measures
      including pain threshold, magnitude estimation of suprathreshold stimulation,
      mechanical temporal summation, as well as CPM, only warm sensation threshold was
      independently associated with lower clinical chest pain intensity (P = 0.01).
      Multivariable regression analysis (R = 0.449; P < 0.0001) revealed an inverse
      independent association between chest pain intensity (P < 0.001) and patient
      delay, whereas efficient CPM was positively associated with prolonged patient
      delay (P = 0.034). The electrocardiography-derived myocardial ischemic area was
      not associated with chest pain intensity or patient delay, indicating that the
      affected ischemic tissue is not a dominant component that determines pain
      response. In conclusion, beyond the perceived chest pain intensity, the
      activation pattern of descending inhibition pathways during coronary occlusion
      affects pain interpretation and behavior during acute coronary occlusion. 

PMID- 25599316
TI  - Contemporary Patterns and Survival Outcome of Adjuvant Systemic Therapy for
      Localized Gastrointestinal Stromal Tumors.
AB  - OBJECTIVES: To describe contemporary patterns of and factors associated with
      adjuvant therapy use and survival outcome after resection of localized
      gastrointestinal stromal tumors (GISTs) using a large contemporary clinical
      database. METHODS: We queried the National Cancer Data Base to identify localized
      GIST cases diagnosed from 2004 to 2011, and used descriptive and logistic
      regression analyses to determine patterns of and factors associated with adjuvant
      therapy. Kaplan-Meier and Cox proportional-hazard model were utilized to generate
      survival probabilities and hazard ratios (HRs). RESULTS: Of 4694 patients, 73.5%
      received surgery alone, and 26.5% received adjuvant therapy during 2004 to 2011.
      Receipt of adjuvant therapy more than doubled between 2006 (13.2%) and 2007
      (30.5%), peaked to 37.9% in 2009, and then decreased to 25.6% in 2011 (P for
      trend<0.0001). Receipt of adjuvant therapy monotonically decreased with older age
      (P for trend<0.0001), and was higher in patients with larger tumor size (>10 cm)
      than those with smaller tumor size (<=5 cm) (44.1% vs. 15.8%; P<0.0001). Patients
      who received adjuvant therapy had 46% lower risk of death than those who received
      surgery alone (HR=0.55; 95% confidence interval, 0.37-0.79; P<0.001); survival
      benefit was statistically significant for GISTs with >10 cm tumor size (HR=0.42;
      95% confidence interval, 0.20-0.89; P=0.02). CONCLUSIONS: In a large nationwide
      dataset, we showed that the use of adjuvant therapy for localized GISTs has
      significantly increased over time and patients treated with adjuvant therapy have
      better survival than patients treated with surgery alone.

PMID- 25599313
TI  - Effects of the triple monoamine uptake inhibitor amitifadine on pain-related
      depression of behavior and mesolimbic dopamine release in rats.
AB  - Pain-related depression of behavior and mood is a key therapeutic target in the
      treatment of pain. Clinical evidence suggests a role for decreased dopamine (DA)
      signaling in pain-related depression of behavior and mood. Similarly, in rats,
      intraperitoneal injection of dilute lactic acid (IP acid) serves as a chemical
      noxious stimulus to produce analgesic-reversible decreases in both (1)
      extracellular DA levels in nucleus accumbens (NAc) and (2) intracranial self
      stimulation (ICSS), an operant behavior reliant on NAc DA. Intraperitonial acid
      induced depression of ICSS is blocked by DA transporter (DAT) inhibitors, but
      clinical viability of selective DAT inhibitors as analgesics is limited by abuse
      potential. Drugs that produce combined inhibition of both DA and serotonin
      transporters may retain efficacy to block pain-related behavioral depression with
      reduced abuse liability. Amitifadine is a "triple uptake inhibitor" that inhibits
      DAT with approximately 5- to 10-fold weaker potency than it inhibits serotonin
      and norepinephrine transporters. This study compared amitifadine effects on IP
      acid-induced depression of NAc DA and ICSS and IP acid-stimulated stretching in
      male Sprague-Dawley rats. Amitifadine blocked IP acid-induced depression of both
      NAc DA and ICSS and IP acid-stimulated stretching. In the absence of the noxious
      stimulus, amitifadine increased NAc levels of both DA and serotonin, and
      behaviorally, amitifadine produced significant but weak abuse-related ICSS
      facilitation. Moreover, amitifadine was more potent to block IP acid-induced
      depression of ICSS than to facilitate control ICSS. These results support
      consideration of amitifadine and related monoamine uptake inhibitors as candidate
      analgesics for treatment of pain-related behavioral depression. 

PMID- 25599317
TI  - Surgery and Adjuvant Radiation for High-risk Skin Adnexal Carcinoma of the Head
      and Neck.
AB  - OBJECTIVES: Skin adnexal carcinoma (SAC) is a rare cutaneous malignancy that
      arises from sebaceous and sweat glands. These carcinomas are believed to behave
      more aggressively than cutaneous squamous cell carcinomas (SCC) with a propensity
      for local recurrence. The role of adjuvant radiotherapy in SAC is undefined.
      METHODS: We retrospectively reviewed all cases of head and neck SAC treated with
      surgery and adjuvant radiation from 2000 to 2012 at a single institution.
      RESULTS: Nine cases were identified. Median age was 67 (range, 52 to 88) years.
      The histologies were: adnexal carcinoma (n=1), adnexal carcinoma with sebaceous
      differentiation (n=1), adnexal carcinoma with squamous differentiation (n=1),
      skin appendage carcinoma (n=1), sclerosing sweat duct carcinoma (n=1), mucinous
      carcinoma (n=1), ductal eccrine adenocarcinoma (n=1), porocarcinoma (n=1), and
      trichilemmal carcinoma (n=1). All tumors were reviewed by a dermatopathologist to
      confirm the SAC diagnosis.All patients had undergone surgery. Indications for
      adjuvant radiation included involved lymph nodes (n=4), perineural invasion
      (n=2), nodal extracapsular extension (n=2), positive margin (n=1), high-grade
      histology (n=6), multifocal disease (n=2), and/or recurrent disease (n=5).
      Radiation was delivered to the primary site alone (n=3), to the draining
      lymphatics alone (n=2), or to both (n=4). One patient received concurrent
      cisplatin. Median dose to the primary site was 60 Gy and to the neck was 50
      Gy.Median follow-up was 4.0 years (range, 0.6 to 11.4 y). Locoregional control
      was 100%. Five-year progression-free survival was 89%. There was 1 acute grade 3
      toxicity and no greater than or equal to grade 2 late toxicities were recorded.
      CONCLUSIONS: Surgery and adjuvant radiation for high-risk SAC offers excellent
      locoregional control with acceptable toxicity.

PMID- 25599318
TI  - Long-term Outcomes and Complications in Pediatric Ewing Sarcoma.
AB  - OBJECTIVES: The objective of this study was to determine treatment outcomes and
      long-term complications in pediatric patients with Ewing Sarcoma treated at the
      British Columbia Cancer Agency (BCCA). METHODS: A retrospective chart review of
      101 pediatric patients (<19 y old) with Ewing Sarcoma diagnosed between 1960 and
      2005 was performed. The Kaplan-Meier survival analysis and Cox regression
      multivariate analysis were used to assess prognostic factors for overall survival
      (OS) and event-free survival (EFS). RESULTS: The median age at diagnosis was 11
      years and the median follow-up for nondeceased patients was 13.5 years. The most
      common primary tumor locations were lower extremity (33%), pelvis (24%), and
      thorax (18%). Fifty percent of patients received surgery, 79% radiotherapy and
      94% chemotherapy. The 5-year OS and EFS for patients with localized disease was
      85% and 73% and for metastatic disease was 27% (P<0.0001) and 28% (P<0.0001),
      respectively. Metastatic disease was an independent predictor of lower OS (hazard
      ratio [HR], 9.5; 95% confidence interval [CI],4.7-19.4; P<0.0001) and EFS (HR,
      4.9; 95% CI, 2.7-8.8; P<0.0001). Extremity tumor location was an independent
      predictor for improved OS (HR, 0.4; 95% CI, 0.2-0.9; P=0.03). The majority (77%)
      of long-term survivors (>=5 y) had long-term complications; the most common were
      musculoskeletal abnormalities (50%) and cardiac toxicity (28%). The actuarial
      second neoplasm risk was 5% at 10 years. CONCLUSIONS: Ewing sarcoma patients with
      localized disease had excellent treatment outcomes at the BCCA. However, the
      majority of patients had chronic complications from treatment. This study
      validates the need for long-term follow-up of Ewing Sarcoma survivors for
      management of late effects.

PMID- 25599319
TI  - Oral Platelet Gel Supernatant Plus Supportive Medical Treatment Versus Supportive
      Medical Treatment in the Management of Radiation-induced Oral Mucositis: A
      Matched Explorative Active Control Trial by Propensity Analysis.
AB  - OBJECTIVES: In this active control trial, the rate of radio-induced WHO grade 3/4
      oral mucositis and the change in quality of life, assessed by OMWQ-HN, were
      measured in subjects with head and neck cancer treated by platelet gel
      supernatant (PGS) and supportive medical treatment versus subjects treated by
      supportive medical treatment alone. MATERIALS AND METHODS: Eighty patients with
      nonmetastatic head and neck cancer underwent curative or adjuvant radiotherapy.
      All patients underwent supportive medical treatment and/or PGS at the beginning
      and during radiotherapy. Sixteen patients received PGS in association with
      supportive medical treatment. To obtain 2 groups virtually randomized for
      important clinical characteristics subjects were matched, by propensity analysis,
      with a group of subjects (64 patients) treated with supportive medical treatment
      alone. RESULTS: Subjects treated with standard supportive treatment experienced
      significant higher WHO grade 3/4 toxicity (55%; 35/64) than subjects treated by
      PGS (13%; 3/16). The reduced toxicity found in PGS group paralleled with the
      evidence that they developed later symptoms with respect to controls. The Cox
      proportional hazard model indicated that patients treated with standard
      supportive medical treatment experienced 2.7-fold increase (hazard ratio=2.7; 95%
      confidence interval, 1.3-5.7) in the occurrence of WHO grade 3/4 toxicity. PGS
      group significantly experienced higher quality of life than control groups as
      measured by OMWQ-HN. A significant decrease in the opioid analgesics usage was
      found in the PGS group. CONCLUSIONS: These preliminary data should be interpreted
      with caution and could serve as a framework around which to design future trials.

PMID- 25599323
TI  - Neoadjuvant therapy for localized pancreatic cancer: support is growing?

PMID- 25599325
TI  - Inferior vena cava filters for prevention of venous thromboembolism in obese
      patients undergoing bariatric surgery: a systematic review.
AB  - OBJECTIVE: The use of inferior vena cava (IVC) filters for prevention of venous
      thromboembolism (VTE) in bariatric surgery is a contentious issue. We aim to
      review the evidence for the use of IVC filters in bariatric surgical patients,
      describe trends in practice, and discuss challenges in developing evidence-based
      guidelines. BACKGROUND: The incidence of VTE in modern bariatric procedures with
      traditional methods of thromboprophylaxis, such as sequential calf compression
      devices and perioperative low molecular weight heparin, is approximately 2%.
      METHODS: A systematic review of the literature was conducted according to PRISMA
      guidelines. We searched Medline up until July 2013 with the terms "bariatric
      filter" and "gastric bypass filter." Two investigators independently screened
      search results according to an agreed list of eligibility criteria. RESULTS:
      Eighteen studies were included. There were no randomized controlled trials. Data
      from controlled cohort studies suggest that those who undergo IVC filter
      insertion preoperatively may be at higher risk of developing deep vein thrombosis
      (DVT) and pulmonary embolism (PE). A small cohort of patients with multiple risk
      factors for VTE benefitted from reduced PE-related mortality after preoperative
      IVC filter insertion. Data from 12 case series reporting VTE outcomes from a
      total of 497 patients who underwent preoperative IVC filter insertion
      demonstrated DVT rates of 0% to 20.8% and PE rates ranging from 0% to 6.4%.
      CONCLUSIONS: Published data reporting the safety and efficacy of IVC filter use
      in bariatric surgical patients is highly heterogeneous. There is no evidence to
      suggest that the potential benefits of IVC filters outweigh the significant risks
      of therapy.

PMID- 25599322
TI  - Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX
      for locally advanced and borderline resectable pancreatic cancer.
AB  - PURPOSE: On the basis of the ACCORD trial, FOLFIRINOX is effective in metastatic
      pancreatic adenocarcinoma (PDAC), making it a rational choice for locally
      advanced PDAC (LA). Aims of this study are to evaluate the accuracy of imaging in
      determining the resectability of PDAC and to determine the surgical and
      clinicopathologic outcomes of pancreatic resections after neoadjuvant FOLFIRINOX
      therapy. PATIENTS AND METHODS: Clinicopathologic data were retrospectively
      collected for surgical PDAC patients receiving neoadjuvant FOLFIRINOX or no
      neoadjuvant therapy between April 2011 and February 2014. Americas Hepato
      Pancreato-Biliary Association/Society of Surgical Oncology/Society for Surgery of
      the Alimentary Tract consensus guidelines defined LA and borderline. Imaging was
      reviewed by a blinded senior pancreatic surgeon. RESULTS: Of 188 patients
      undergoing resection for PDAC, 40 LA/borderline received FOLFIRINOX and 87
      received no neoadjuvant therapy. FOLFIRINOX resulted in a significant decrease in
      tumor size, yet 19 patients were still classified as LA and 9 as borderline.
      Despite post-FOLFIRINOX imaging suggesting continued unresectability, 92% had an
      R0 resection. When compared with no neoadjuvant therapy, FOLFIRINOX resulted in
      significantly longer operative times (393 vs 300 minutes) and blood loss (600 vs
      400 mL), but significantly lower operative morbidity (36% vs 63%) and no
      postoperative pancreatic fistulas. Length of stay (6 vs 7 days), readmissions
      (20% vs 30%), and mortality were equivalent (1% vs 0%). On final pathology, the
      FOLFIRINOX group had a significant decrease in lymph node positivity (35% vs 79%)
      and perineural invasion (72% vs 95%). Median follow-up was 11 months with a
      significant increase in overall survival with FOLFIRINOX. CONCLUSIONS: After
      neoadjuvant FOLFIRINOX imaging no longer predicts unresectability. Traditional
      pathologic predictors of survival are improved, and morbidity is decreased in
      comparison to patients with clearly resectable cancers at the time of
      presentation.

PMID- 25599324
TI  - Total pancreatectomy with islet autotransplantation: summary of an NIDDK
      workshop.
AB  - A workshop sponsored by the National Institute of Diabetes and Digestive and
      Kidney Diseases focused on research gaps and opportunities in total
      pancreatectomy with islet autotransplantation (TPIAT) for the management of
      chronic pancreatitis. The session was held on July 23, 2014 and structured into 5
      sessions: (1) patient selection, indications, and timing; (2) technical aspects
      of TPIAT; (3) improving success of islet autotransplantation; (4) improving
      outcomes after total pancreatectomy; and (5) registry considerations for TPIAT.
      The current state of knowledge was reviewed; knowledge gaps and research needs
      were specifically highlighted. Common themes included the need to identify which
      patients best benefit from and when to intervene with TPIAT, current limitations
      of the surgical procedure, diabetes remission and the potential for improvement,
      opportunities to better address pain remission, GI complications in this
      population, and unique features of children with chronic pancreatitis considered
      for TPIAT. The need for a multicenter patient registry that specifically
      addresses the complexities of chronic pancreatitis and total pancreatectomy
      outcomes and postsurgical diabetes outcomes was repeatedly emphasized. 

PMID- 25599327
TI  - Reply to letter: "Determinant-based classification of severity of acute
      pancreatitis: have we really reached consensus?".

PMID- 25599328
TI  - Association of amiodarone use with acute pancreatitis in patients with atrial
      fibrillation: a nested case-control study.

PMID- 25599326
TI  - The status of contemporary image-guided modalities in oncologic surgery.
AB  - OBJECTIVE: To review the current trends in optical imaging to guide oncologic
      surgery. BACKGROUND: Surgical resection remains the cornerstone of therapy for
      patients with early stage solid malignancies and more than half of all patients
      with cancer undergo surgery each year. The technical ability of the surgeon to
      obtain clear surgical margins at the initial resection remains crucial to improve
      overall survival and long-term morbidity. Current resection techniques are
      largely based on subjective and subtle changes associated with tissue distortion
      by invasive cancer. As a result, positive surgical margins occur in a significant
      portion of tumor resections, which is directly correlated with a poor outcome.
      METHODS: A comprehensive review of studies evaluating optical imaging techniques
      is performed. RESULTS: A variety of cancer imaging techniques have been adapted
      or developed for intraoperative surgical guidance that have been shown to improve
      functional and oncologic outcomes in randomized clinical trials. There are also a
      large number of novel, cancer-specific contrast agents that are in early stage
      clinical trials and preclinical development that demonstrate significant promise
      to improve real-time detection of subclinical cancer in the operative setting.
      CONCLUSIONS: There has been an explosion of intraoperative imaging techniques
      that will become more widespread in the next decade.

PMID- 25599329
TI  - Out-of-hospital mortality among patients receiving methadone for noncancer pain.
AB  - IMPORTANCE: Growing methadone use in pain management has raised concerns
      regarding its safety relative to other long-acting opioids. Methadone
      hydrochloride may increase the risk for lethal respiratory depression related to
      accidental overdose and life-threatening ventricular arrhythmias. OBJECTIVE: To
      compare the risk of out-of-hospital death in patients receiving methadone for
      noncancer pain with that in comparable patients receiving sustained-release (SR)
      morphine sulfate. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study
      was conducted using Tennessee Medicaid records from 1997 through 2009. The cohort
      included patients receiving morphine SR or methadone who were aged 30 to 74
      years, did not have cancer or another life-threatening illness, and were not in a
      hospital or nursing home. At cohort entry, 32 742 and 6014 patients had filled a
      prescription for morphine SR or methadone, respectively. The patients' median age
      was 48 years, 57.9% were female, and comparable proportions had received
      cardiovascular, psychotropic, and other musculoskeletal medications. Nearly 90%
      of the patients received the opioid for back pain or other musculoskeletal pain.
      The median doses prescribed for morphine SR and methadone were 90 mg/d and 40
      mg/d, respectively. MAIN OUTCOMES AND MEASURES: The primary study end point was
      out-of-hospital mortality, given that opioid-related deaths typically occur
      outside the hospital. RESULTS: There were 477 deaths during 28 699 person-years
      of follow-up (ie, 166 deaths per 10 000 person-years). After control for study
      covariates, patients receiving methadone had a 46% increased risk of death during
      the follow-up period, with an adjusted hazard ratio (HR) of 1.46 (95% CI, 1.17
      1.83; P < .001), resulting in 72 (95% CI, 27-130) excess deaths per 10 000 person
      years of follow-up. Methadone doses of 20 mg/d or less, the lowest dose quartile,
      were associated with an increased risk of death (HR, 1.59; 95% CI, 1.01-2.51, P =
      .046) relative to a comparable dose of morphine SR (<60 mg/d). CONCLUSIONS AND
      RELEVANCE: The increased risk of death observed for patients receiving methadone
      in this retrospective cohort study, even for low doses, supports recommendations
      that it should not be a drug of first choice for noncancer pain.

PMID- 25599330
TI  - Cognitive resilience to apolipoprotein E epsilon4: contributing factors in black
      and white older adults.
AB  - IMPORTANCE: Apolipoprotein E (APOE) epsilon4 is an established risk factor for
      cognitive decline and the development of dementia, but other factors may help to
      minimize its effects. OBJECTIVE: Using APOE epsilon4 as an indicator of high
      risk, we investigated factors associated with cognitive resilience among black
      and white older adults who are APOE epsilon4 carriers. DESIGN, SETTING, AND
      PARTICIPANTS: Participants included 2487 community-dwelling older (aged 69-80
      years at baseline) black and white adults examined at 2 community clinics in the
      prospective cohort Health, Aging, and Body Composition (Health ABC) study. The
      baseline visits occurred from May 1997 through June 1998. Our primary analytic
      cohort consisted of 670 APOE epsilon4 carriers (329 black and 341 white
      participants) who were free of cognitive impairment at baseline and underwent
      repeated cognitive testing during an 11-year follow-up (through 2008) using the
      Modified Mini-Mental State Examination. MAIN OUTCOMES AND MEASURES: We stratified
      all analyses by race. Using the Modified Mini-Mental State Examination scores, we
      assessed normative cognitive change in the entire cohort (n = 2487) and
      classified the APOE epsilon4 carriers as being cognitively resilient vs
      nonresilient by comparing their cognitive trajectories with those of the entire
      cohort. We then conducted bivariate analyses and multivariable random forest and
      logistic regression analyses to explore factors predictive of cognitive
      resilience in APOE epsilon4 carriers. RESULTS: Among white APOE epsilon4
      carriers, the strongest predictors of cognitive resilience were, in relative
      order of importance, no recent negative life events, a higher literacy level,
      advanced age, a higher educational level, and more time spent reading. Among
      black APOE epsilon4 carriers, the strongest predictors of cognitive resilience
      were, in relative order of importance, a higher literacy level, a higher
      educational level, female sex, and the absence of diabetes mellitus. In follow-up
      logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50
      [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college
      graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted
      OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant
      independent effects in predicting cognitive resilience among white APOE epsilon4
      carriers. Among black APOE epsilon4 carriers, a higher literacy level (adjusted
      OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for
      high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54
      5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI,
      1.14-5.62]) had significant independent effects in predicting cognitive
      resilience. CONCLUSIONS AND RELEVANCE: Although APOE epsilon4 carriers are at
      high risk for cognitive decline, our findings suggest possible intervention
      targets, including the enhancement of cognitive reserve and improvement of other
      psychosocial and health factors, to promote cognitive resilience among black and
      white APOE epsilon4 carriers.

PMID- 25599331
TI  - Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to
      both development of renal insufficiency and mortality risk in chronic kidney
      disease.
AB  - RATIONALE: Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite of
      dietary choline, phosphatidylcholine (lecithin), and l-carnitine, is elevated in
      chronic kidney diseases (CKD) and associated with coronary artery disease
      pathogenesis. OBJECTIVE: To both investigate the clinical prognostic value of
      TMAO in subjects with versus without CKD, and test the hypothesis that TMAO plays
      a direct contributory role in the development and progression of renal
      dysfunction. METHODS AND RESULTS: We first examined the relationship between
      fasting plasma TMAO and all-cause mortality over 5-year follow-up in 521 stable
      subjects with CKD (estimated glomerular filtration rate, <60 mL/min per 1.73
      m(2)). Median TMAO level among CKD subjects was 7.9 MUmol/L (interquartile range,
      5.2-12.4 MUmol/L), which was markedly higher (P<0.001) than in non-CKD subjects
      (n=3166). Within CKD subjects, higher (fourth versus first quartile) plasma TMAO
      level was associated with a 2.8-fold increased mortality risk. After adjustments
      for traditional risk factors, high-sensitivity C-reactive protein, estimated
      glomerular filtration rate, elevated TMAO levels remained predictive of 5-year
      mortality risk (hazard ratio, 1.93; 95% confidence interval, 1.13-3.29; P<0.05).
      TMAO provided significant incremental prognostic value (net reclassification
      index, 17.26%; P<0.001 and differences in area under receiver operator
      characteristic curve, 63.26% versus 65.95%; P=0.036). Among non-CKD subjects,
      elevated TMAO levels portend poorer prognosis within cohorts of high and low
      cystatin C. In animal models, elevated dietary choline or TMAO directly led to
      progressive renal tubulointerstitial fibrosis and dysfunction. CONCLUSIONS:
      Plasma TMAO levels are both elevated in patients with CKD and portend poorer long
      term survival. Chronic dietary exposures that increase TMAO directly contributes
      to progressive renal fibrosis and dysfunction in animal models.

PMID- 25599333
TI  - The ARRIBA concept: adequate resorption of ribavirin.
AB  - BACKGROUND: Adequate ribavirin exposure is essential for optimal sustained
      virological response (SVR) rates in chronic HCV treatment. It has been proposed
      that the area under the concentration-time curve up to 4 h after intake of
      ribavirin (AUC0-4 h) of the first weight-based ribavirin dose should be >=1.755
      mg*h/l to guarantee the highest chance of SVR. Our ARRIBA concept comprises a
      test dose of ribavirin to select the optimal starting dose to achieve adequate
      exposure. This study aims to evaluate whether adequate exposure can be achieved
      after dose advice based on the AUC0-4 h of a single weight-based ribavirin test
      dose. METHODS: (Formerly) HCV-infected subjects received a single weight-based
      ribavirin test dose (<75 kg: 400 mg; >=75 kg: 600 mg) and the AUC0-4 h was
      calculated. If ribavirin AUC0-4 h was >=1.755 mg*h/l, subjects received the same
      dose 4 weeks later; if the AUC0-4 h was <1.755 mg*h/l, an adjusted dose was
      administered. The ribavirin AUC0-4 h was recorded again. The primary outcome was
      the proportion of subjects with an AUC0-4 h >=1.755 mg*h/l after the second dose.
      RESULTS: A total of 26 subjects were included. The geometric mean (95% CI)
      ribavirin AUC0-4 h was 1.67 (1.44-1.92) mg*h/l with 9 subjects (35%) reaching the
      target AUC on day 1. Thus, on day 29, 17 subjects (65%) received an adjusted
      dose. The geometric mean (95% CI) AUC0-4 h increased to 1.90 (1.62-2.21) mg*h/l
      and then 16 subjects (62%) had an AUC0-4 h >=1.755 mg*h/l, which is significantly
      higher than day 1 (P<0.05). CONCLUSIONS: Our ARRIBA concept of a ribavirin test
      dose, with dose adjustment if necessary, leads to an increased proportion of
      patients with an AUC>=1.755 mg*h/l compared to traditional weight-based ribavirin
      dosing.

PMID- 25599332
TI  - Canonical wnt signaling regulates atrioventricular junction programming and
      electrophysiological properties.
AB  - RATIONALE: Proper patterning of the atrioventricular canal (AVC) is essential for
      delay of electrical impulses between atria and ventricles, and defects in AVC
      maturation can result in congenital heart disease. OBJECTIVE: To determine the
      role of canonical Wnt signaling in the myocardium during AVC development. METHODS
      AND RESULTS: We used a novel allele of beta-catenin that preserves beta-catenin's
      cell adhesive functions but disrupts canonical Wnt signaling, allowing us to
      probe the effects of Wnt loss of function independently. We show that the loss of
      canonical Wnt signaling in the myocardium results in tricuspid atresia with
      hypoplastic right ventricle associated with the loss of AVC myocardium. In
      contrast, ectopic activation of Wnt signaling was sufficient to induce formation
      of ectopic AV junction-like tissue as assessed by morphology, gene expression,
      and electrophysiological criteria. Aberrant AVC development can lead to
      ventricular pre-excitation, a characteristic feature of Wolff-Parkinson-White
      syndrome. We demonstrate that postnatal activation of Notch signaling
      downregulates canonical Wnt targets within the AV junction. Stabilization of beta
      catenin protein levels can rescue Notch-mediated ventricular pre-excitation and
      dysregulated ion channel gene expression. CONCLUSIONS: Our data demonstrate that
      myocardial canonical Wnt signaling is an important regulator of AVC maturation
      and electric programming upstream of Tbx3. Our data further suggest that
      ventricular pre-excitation may require both morphological patterning defects, as
      well as myocardial lineage reprogramming, to allow robust conduction across
      accessory pathway tissue.

PMID- 25599335
TI  - Analysis of the hierarchical structure of the B. subtilis transcriptional
      regulatory network.
AB  - The transcriptional regulation of gene expression is orchestrated by complex
      networks of interacting genes. Increasing evidence indicates that these
      'transcriptional regulatory networks' (TRNs) in bacteria have an inherently
      hierarchical architecture, although the design principles and the specific
      advantages offered by this type of organization have not yet been fully
      elucidated. In this study, we focussed on the hierarchical structure of the TRN
      of the gram-positive bacterium Bacillus subtilis and performed a comparative
      analysis with the TRN of the gram-negative bacterium Escherichia coli. Using a
      graph-theoretic approach, we organized the transcription factors (TFs) and sigma
      factors in the TRNs of B. subtilis and E. coli into three hierarchical levels
      (Top, Middle and Bottom) and studied several structural and functional properties
      across them. In addition to many similarities, we found also specific
      differences, explaining the majority of them with variations in the distribution
      of sigma-factors across the hierarchical levels in the two organisms. We then
      investigated the control of target metabolic genes by transcriptional regulators
      to characterize the differential regulation of three distinct metabolic
      subsystems (catabolism, anabolism and central energy metabolism). These results
      suggest that the hierarchical architecture that we observed in B. subtilis
      represents an effective organization of its TRN to achieve flexibility in
      response to a wide range of diverse stimuli. 

PMID- 25599334
TI  - Objective Versus Self-Reported Physical Activity in Overweight and Obese Young
      Adults.
AB  - BACKGROUND: To compare moderate-to-vigorous intensity physical activity (MVPA)
      assessed via questionnaires to an objective measure of MVPA in overweight or
      obese young adults. METHODS: MVPA was assessed in 448 [median BMI = 31.2
      (Interquartile Range: 28.5-34.3) kg/m2] young adults [median age: 30.9
      (Interquartile Range: 27.8-33.7) years]. Measures included the SenseWear Armband
      (MVPAOBJ), the Paffenbarger Questionnaire (MVPAPAFF), and the Global Physical
      Activity Questionnaire (GPAQ). The GPAQ was used to compute total MVPA (MVPAGPAQ
      TOTAL) and MVPA from transportation and recreation (MVPAGPAQ-REC). RESULTS: The
      association between MVPAOBJ and MVPAPAFF was rs = 0.40 (P < .0001). Associations
      between MVPAOBJ and MVPAGPAQ-TOTAL and MVPAGPAQ-REC were rs = 0.19 and rs = 0.32,
      respectively (P < .0001). MVPAGPAQ-TOTAL was significantly greater than MVPAOBJ
      (P < .0001). Median differences in MET-min/week between MVPAOBJ and MVPAPAFF or
      MVPAGPAQ-REC were not significantly different from zero. There was proportional
      bias between each self-reported measure of MVPA and MVPAOBJ. There were
      significant associations between all measures of MVPA and fitness. MVPAOBJ was
      significantly associated with BMI and percent body fat. CONCLUSIONS: Objective
      and self-reported measures of MVPA are weakly to moderately correlated, with
      substantial differences between measures. MVPAOBJ provided predictive validity
      with fitness, BMI, and percent body fat. Thus, an objective measure of MVPA may
      be preferred to self-report in young adults.

PMID- 25599337
TI  - X-shaped benzoylbenzophenone derivatives with crossed donors and acceptors for
      highly efficient thermally activated delayed fluorescence.
AB  - Thermally activated delayed fluorescence (TADF) materials based on
      benzoylbenzophenone, AcPmBPX and PxPmBPX, were designed and synthesized. Organic
      light-emitting diodes using these materials as emitters exhibited high external
      electroluminescence quantum efficiencies of up to 11%. 

PMID- 25599336
TI  - Complementary analysis of the hard and soft protein corona: sample preparation
      critically effects corona composition.
AB  - Here we demonstrate how a complementary analysis of nanocapsule-protein
      interactions with and without application media allows gaining insights into the
      so called hard and soft protein corona. We have investigated how both human
      plasma and individual proteins (human serum albumin (HSA), apolipoprotein A-I
      (ApoA-I)) adsorb and interact with hydroxyethyl starch (HES) nanocapsules
      possessing different functionalities. To analyse the hard protein corona we used
      sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and a
      protein quantitation assay. No significant differences were observed with regards
      to the hard protein corona. For analysis of the soft protein corona we
      characterized the nanocapsule-protein interaction with isothermal titration
      calorimetry (ITC) and dynamic light scattering (DLS). DLS and ITC measurements
      revealed that a high amount of plasma proteins were adsorbed onto the capsules'
      surface. Although HSA was not detected in the hard protein corona, ITC
      measurements indicated the adsorption of an HSA amount similar to plasma with a
      low binding affinity and reaction heat. In contrast, only small amounts of ApoA-I
      protein adsorb to the capsules with high binding affinities. Through a comparison
      of these methods we have identified ApoA-I to be a component of the hard protein
      corona and HSA as a component of the soft corona. We demonstrate a pronounced
      difference in the protein corona observed depending on the type of
      characterization technique applied. As the biological identity of a particle is
      given by the protein corona it is crucial to use complementary characterization
      techniques to analyse different aspects of the protein corona. 

PMID- 25599338
TI  - Orthokeratology for myopia control: a meta-analysis.
AB  - PURPOSE: To conduct a meta-analysis on the effects of orthokeratology in slowing
      myopia progression. METHODS: A literature search was performed in PubMed, Embase,
      and the Cochrane Library. Methodological quality of the literature was evaluated
      according to the Jadad score. The statistical analysis was carried out using
      RevMan 5.2.6 software. RESULTS: The present meta-analysis included seven studies
      (two randomized controlled trials and five nonrandomized controlled trials) with
      435 subjects (orthokeratology group, 218; control group, 217) aged 6 to 16 years.
      The follow-up time was 2 years for the seven studies. The weighted mean
      difference was -0.26 mm (95% confidence interval, -0.31 to -0.21; p < 0.001) for
      axial length elongation based on data from seven studies and -0.18 mm (95%
      confidence interval, -0.33 to -0.03; p = 0.02) for vitreous chamber depth
      elongation based on data from two studies. CONCLUSIONS: Our results suggest that
      orthokeratology may slow myopia progression in children. Further large-scale
      studies are needed to substantiate the current result and to investigate the long
      term effects of orthokeratology in myopia control.

PMID- 25599339
TI  - Low-vision service provision by optometrists: a Canadian nationwide survey.
AB  - PURPOSE: To document the degree to which Canadian optometrists are involved in
      the provision of low-vision (LV) care and their referral patterns. To investigate
      the barriers to providing optometric low-vision services (LVS). METHODS:
      Practicing optometrists across Canada were randomly sampled and invited to
      participate in a questionnaire that included questions on personal profile,
      primary practice profile, levels of LV care offered, patterns of referral, and
      barriers to provision of LV care. Questions included a combination of multiple
      choice and open-ended formats, and included hypothetical cases. RESULTS: A total
      of 459 optometrists responded (response rate, 24.8%). Optometrists estimated that
      1% (range, 0 to 100%) of their patients were LV patients yet also estimated that
      10% of their patients had acuity equal to or worse than 20/40. Thirty-five
      percent of respondents indicated that their primary practice offered LV care,
      75.6% would manage a patient with minimum disability and simple goals themselves,
      whereas 10.7% would manage a patient with more than minimal visual disability who
      needed more specialized LV devices (e.g., telescopes, electronic aids, and custom
      designed microscopes); 84.3% of optometrists would assess for basic magnification
      and lighting in a hypothetical patient with early age-related macular
      degeneration, whereas 15% would undertake full LV rehabilitation in advanced age
      related macular degeneration. Optometrists commonly referred to CNIB (formerly
      the Canadian National Institute for the Blind), yet only 10.7% of respondents
      almost always received a written report after referral. Those who would not
      undertake LV assessment stated that they lacked the knowledge, equipment, or
      experience; that LV assessment is too time consuming; and that the cost is too
      prohibitive. CONCLUSIONS: This is the first comprehensive study of LVS provision
      by optometrists in Canada. In order for optometrists to become more involved in
      LVS, there is a need for more LV education, provincial health coverage of
      optometric LVS, and better collaboration communication between LV providers.

PMID- 25599340
TI  - Scleral lens tolerance after corneal cross-linking for keratoconus.
AB  - PURPOSE: Subjective and objective evaluation of scleral lens tolerance and
      fitting before and after corneal cross-linking (CXL) for progressive keratoconus.
      METHODS: In this prospective cohort, evaluations were made of 18 unilateral eyes
      in patients who underwent CXL and had been wearing scleral lenses before the
      procedure. All the patients gave informed consent; they were able to cooperate
      with the study, were eligible for CXL, had been wearing well-fitting scleral
      lenses for at least 3 months, and had no other active ocular disease. Data were
      collected before and 1 year after CXL. Outcome measures were changes in clinical
      and subjective scleral lens performance. The following components were studied:
      scleral lens corrected distance visual acuity, scleral lens specifications,
      scleral lens fit, wearing time, and subjective measures on visual analogue scale
      questionnaires (1 to 100 mm). RESULTS: There was no significant change in scleral
      lens corrected distance visual acuity (p = 0.632). Sixty-one percent of eyes
      needed a scleral lens fit and/or power change. Wearing time (median, 16 hours per
      day) and subjective tolerance were found to be stable. CONCLUSIONS: Scleral lens
      tolerance after CXL appeared to be stable.

PMID- 25599341
TI  - Cognitive and behavioural aspects of Prader-Willi syndrome.
AB  - PURPOSE OF REVIEW: To provide a review of the recent advances in the diagnosis
      and treatment of psychiatric disorders in Prader-Willi syndrome (PWS). RECENT
      FINDINGS: Research in the last 12 months has provided a descriptive prognosis of
      psychosis in PWS and highlighted the possible genes associated with the increased
      risk of psychosis for those with maternal uniparental disomy (mUPD). Several
      studies investigating social and communication skills have shown people with PWS
      to have difficulty with core, receptive and expressive language skills,
      interpreting emotional valence in faces, playing with children of their own age,
      understanding personal space and a developmental delay in the theory of mind.
      These social and communication deficits are often more pronounced in those with
      mUPD. Two recent clinical trials of oxytocin provide mixed results and highlight
      the need for an improved understanding of the neurobiological characteristics of
      the PWS brain. A recent pilot study suggests N-acetylcysteine may be a viable
      treatment for skin picking. SUMMARY: Recent advances have contributed to our
      understanding of the emotional and behavioural problems associated with PWS, and
      provided directions for further research.

PMID- 25599343
TI  - Lithium storage in disordered graphitic materials: a semi-quantitative study of
      the relationship between structure disordering and capacity.
AB  - The application of the graphitic anode is restricted by its low theoretical
      specific capacity of 372 mA h g(-1). Higher capacity can be achieved in the
      graphitic anode by modifying its structure, but the detailed storage mechanism is
      still not clear. In this work, the mechanism of the lithium storage in a
      disordered graphitic structure has been systematically studied. It is found that
      the enhanced capacity of the distorted graphitic structure does not come from
      lithium-intercalation, but through a capacitive process, which depends on the
      disordering degree and the porous structure. 

PMID- 25599342
TI  - Inflammation and neuroprotection in traumatic brain injury.
AB  - IMPORTANCE: Traumatic brain injury (TBI) is a significant public health concern
      that affects individuals in all demographics. With increasing interest in the
      medical and public communities, understanding the inflammatory mechanisms that
      drive the pathologic and consequent cognitive outcomes can inform future research
      and clinical decisions for patients with TBI. OBJECTIVES: To review known
      inflammatory mechanisms in TBI and to highlight clinical trials and
      neuroprotective therapeutic manipulations of pathologic and inflammatory
      mechanisms of TBI. EVIDENCE REVIEW: We searched articles in PubMed published
      between 1960 and August 1, 2014, using the following keywords: traumatic brain
      injury, sterile injury, inflammation, astrocytes, microglia, monocytes,
      macrophages, neutrophils, T cells, reactive oxygen species, alarmins, danger
      associated molecular patterns, purinergic receptors, neuroprotection, and
      clinical trials. Previous clinical trials or therapeutic studies that involved
      manipulation of the discussed mechanisms were considered for inclusion. The final
      list of selected studies was assembled based on novelty and direct relevance to
      the primary focus of this review. FINDINGS: Traumatic brain injury is a diverse
      group of sterile injuries induced by primary and secondary mechanisms that give
      rise to cell death, inflammation, and neurologic dysfunction in patients of all
      demographics. Pathogenesis is driven by complex, interacting mechanisms that
      include reactive oxygen species, ion channel and gap junction signaling,
      purinergic receptor signaling, excitotoxic neurotransmitter signaling,
      perturbations in calcium homeostasis, and damage-associated molecular pattern
      molecules, among others. Central nervous system resident and peripherally derived
      inflammatory cells respond to TBI and can provide neuroprotection or participate
      in maladaptive secondary injury reactions. The exact contribution of inflammatory
      cells to a TBI lesion is dictated by their anatomical positioning as well as the
      local cues to which they are exposed. CONCLUSIONS AND RELEVANCE: The mechanisms
      that drive TBI lesion development as well as those that promote repair are
      exceedingly complex and often superimposed. Because pathogenic mechanisms can
      diversify over time or even differ based on the injury type, it is important that
      neuroprotective therapeutics be developed and administered with these variables
      in mind. Due to its complexity, TBI has proven particularly challenging to treat;
      however, a number of promising therapeutic approaches are now under pre-clinical
      development, and recent clinical trials have even yielded a few successes. Given
      the worldwide impact of TBI on the human population, it is imperative that
      research remains active in this area and that we continue to develop therapeutics
      to improve outcome in afflicted patients.

PMID- 25599344
TI  - The fungal cerato-platanin protein EPL1 forms highly ordered layers at
      hydrophobic/hydrophilic interfaces.
AB  - Cerato-platanin proteins (CPPs) and hydrophobins are two classes of small,
      secreted proteins that are exclusively found in fungi. CPPs are known as chitin
      binding proteins, and were recently also shown to form protein layers at
      air/water interfaces, but the features of these layers were not investigated on
      the molecular level yet. In this study, by means of atomic force microscopy
      (AFM), EPL1, a member of the CPP family was shown to form highly ordered
      monolayers at a hydrophobic surface/liquid-interface. Furthermore, two new
      hydrophobins were analysed, and the influence of EPL1 on hydrophobin layers was
      studied in situ. Hydrophobins are amphiphilic proteins that are able to self
      assemble at hydrophobic/hydrophilic interfaces, thereby inverting the polarity of
      the surface. This renders fungal growth structures such as spores water
      repellent. The combination of AFM data and wettability experiments led to the
      conclusion that in presence of both, hydrophobins and EPL1, a previously unknown
      hybrid layer is formed. This mixed protein layer is on one hand not inverting but
      enhancing the hydrophobicity of HOPG (highly oriented pyrolytic graphite),
      typical for EPL1, and on the other hand, it is stable and water insoluble, which
      is reminiscent of hydrophobin layers. 

PMID- 25599345
TI  - Single molecule level plasmonic catalysis - a dilution study of p-nitrothiophenol
      on gold dimers.
AB  - Surface plasmons on isolated gold dimers can initiate intermolecular reactions of
      adsorbed p-nitrothiophenol. At the single molecule level when dimerization is not
      possible an intramolecular reaction can be observed. Experimental evidence
      indicates that plasmon-induced hot electrons provide the required activation
      energy. 

PMID- 25599346
TI  - Combination antifungal therapy for invasive aspergillosis: a randomized trial.
AB  - BACKGROUND: Invasive aspergillosis (IA) is associated with poor outcomes in
      patients with hematologic malignancies (HMs) and hematopoietic cell
      transplantation (HCT). Small studies suggest a role for combination antifungal
      therapy. OBJECTIVE: To assess the safety and efficacy of voriconazole and
      anidulafungin compared with voriconazole monotherapy for treatment of IA. DESIGN:
      Randomized, double-blind, placebo-controlled multicenter trial.
      (ClinicalTrials.gov: NCT00531479). SETTING: 93 international sites. PATIENTS: 454
      patients with HM or HCT and suspected or documented IA were randomly assigned to
      treatment with voriconazole and anidulafungin or placebo. Primary analysis was
      done in the modified intention-to-treat population of 277 patients in whom IA was
      confirmed. MEASUREMENTS: The primary outcome was 6-week mortality; secondary
      outcomes included 12-week mortality, mortality in major subgroups, and safety
      measures. RESULTS: Mortality rates at 6 weeks were 19.3% (26 of 135) for
      combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2
      percentage points [95% CI, -19.0 to 1.5]; P  = 0.087). Secondary mortality
      outcomes favored combination therapy. Multivariable regression analysis suggested
      that maximum galactomannan value, Karnofsky score, and baseline platelet count
      had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis
      established by radiographic findings and maximum galactomannan positivity. In a
      post hoc analysis of this dominant subgroup, 6-week mortality was lower in
      combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110];
      difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety
      measures, including hepatotoxicity, were not different. LIMITATIONS: Mortality at
      6 weeks was higher than expected, and the difference in mortality was lower than
      expected, which reduced power to detect a treatment effect. Enrollment was
      restricted to patients with HM or HCT, which limited generalizability.
      CONCLUSION: Compared with voriconazole monotherapy, combination therapy with
      anidulafungin led to higher survival in subgroups of patients with IA.
      Limitations in power preclude definitive conclusions about superiority. PRIMARY
      FUNDING SOURCE: Pfizer.

PMID- 25599347
TI  - Factors associated with lack of viral suppression at delivery among highly active
      antiretroviral therapy-naive women with HIV: a cohort study.
AB  - BACKGROUND: A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is
      a risk factor for mother-to-child transmission and poor maternal health.
      OBJECTIVE: To identify factors associated with detectable VL at delivery despite
      initiation of highly active antiretroviral therapy (HAART) during pregnancy.
      DESIGN: Multicenter observational study. (ClinicalTrial.gov: NCT00028145).
      SETTING: 67 U.S. AIDS clinical research sites. PATIENTS: Pregnant women with HIV
      who initiated HAART during pregnancy. MEASUREMENTS: Descriptive summaries and
      associations among sociodemographic, HIV disease, and treatment characteristics;
      pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery.
      RESULTS: Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had
      detectable VL at delivery. Factors associated with detectable VL included
      multiparity (16.4% vs. 8.0% nulliparity; P = 0.002), black ethnicity (17.6% vs.
      6.6% Hispanic and 6.6% white; P < 0.001), 11th grade education or less (17.6% vs.
      12.1% had a high school diploma; P = 0.013), initiation of HAART in the third
      trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P
      = 0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0%
      during the current pregnancy; P = 0.051), and having the first prenatal visit in
      the third trimester (33.3% vs. 14.3% and 10.5% in the second and third
      trimesters, respectively; P = 0.002). Women who had treatment interruptions or
      reported poor medication adherence were more likely to have detectable VL at
      delivery. LIMITATION: Data on many covariates were incomplete because women
      entered the study at varying times during pregnancy. CONCLUSION: A total of 13.1%
      of women who initiated HAART during pregnancy had detectable VL at delivery. The
      timing of HAART initiation and prenatal care, along with medication adherence
      during pregnancy, were associated with detectable VL at delivery. Social factors,
      including ethnicity and education, may help identify women who could benefit from
      focused efforts to promote early HAART initiation and adherence. PRIMARY FUNDING
      SOURCE: U.S. Department of Health and Human Services.

PMID- 25599349
TI  - Overuse of testing in preoperative evaluation and syncope: a survey of
      hospitalists.
AB  - BACKGROUND: Health care reform efforts and initiatives seek to improve quality
      and reduce costs by eliminating unnecessary care. However, little is known about
      overuse and its drivers, especially in hospitals. OBJECTIVE: To assess the extent
      of and factors associated with overuse of testing in U.S. hospitals. DESIGN:
      National survey of practice patterns for 2 common clinical vignettes:
      preoperative evaluation and syncope. Respondents were randomly selected and
      randomly provided 1 of 4 versions of each vignette. Each version contained
      identical clinical information but varied in factors that could change physician
      behavior. Respondents were asked to identify what they believed most hospitalists
      at their institution would recommend in each vignette. SETTING: Mailed survey
      conducted from June through October 2011. PARTICIPANTS: Physicians practicing
      adult hospital medicine in the United States. MEASUREMENTS: Responses indicating
      overuse (more testing than recommended by American College of Cardiology/American
      Heart Association guidelines). RESULTS: 68% (1020 of 1500) of hospitalists
      responded. They reported overuse in 52% to 65% of the preoperative evaluation
      vignettes and 82% to 85% of the syncope vignettes. Overuse more frequently
      resulted from a physician's desire to reassure patients or themselves than an
      incorrect belief that it was clinically indicated (preoperative evaluation, 63%
      vs. 37%; syncope, 69% vs. 31%; P < 0.001 for each). LIMITATION: Survey responses
      may not represent actual clinical choices. CONCLUSION: Physicians reported
      substantial overuse in 2 common clinical situations in the hospital. Improving
      provider knowledge of guidelines may help reduce overuse, but despite awareness
      of the guidelines, physicians often deviate from them to reassure patients or
      themselves. PRIMARY FUNDING SOURCE: Blue Cross Blue Shield of Michigan
      Foundation, Department of Veterans Affairs Center for Clinical Management
      Research, University of Michigan Specialist-Hospitalist Allied Research Program,
      and Ann Arbor Veterans Affairs/University of Michigan Patient Safety Enhancement
      Program.

PMID- 25599350
TI  - Sedentary time and its association with risk for disease incidence, mortality,
      and hospitalization in adults: a systematic review and meta-analysis.
AB  - BACKGROUND: The magnitude, consistency, and manner of association between
      sedentary time and outcomes independent of physical activity remain unclear.
      PURPOSE: To quantify the association between sedentary time and hospitalizations,
      all-cause mortality, cardiovascular disease, diabetes, and cancer in adults
      independent of physical activity. DATA SOURCES: English-language studies in
      MEDLINE, PubMed, EMBASE, CINAHL, Cochrane Library, Web of Knowledge, and Google
      Scholar databases were searched through August 2014 with hand-searching of in
      text citations and no publication date limitations. STUDY SELECTION: Studies
      assessing sedentary behavior in adults, adjusted for physical activity and
      correlated to at least 1 outcome. DATA EXTRACTION: Two independent reviewers
      performed data abstraction and quality assessment, and a third reviewer resolved
      inconsistencies. DATA SYNTHESIS: Forty-seven articles met our eligibility
      criteria. Meta-analyses were performed on outcomes for cardiovascular disease and
      diabetes (14 studies), cancer (14 studies), and all-cause mortality (13 studies).
      Prospective cohort designs were used in all but 3 studies; sedentary times were
      quantified using self-report in all but 1 study. Significant hazard ratio (HR)
      associations were found with all-cause mortality (HR, 1.240 [95% CI, 1.090 to
      1.410]), cardiovascular disease mortality (HR, 1.179 [CI, 1.106 to 1.257]),
      cardiovascular disease incidence (HR, 1.143 [CI, 1.002 to 1.729]), cancer
      mortality (HR, 1.173 [CI, 1.108 to 1.242]), cancer incidence (HR, 1.130 [CI,
      1.053 to 1.213]), and type 2 diabetes incidence (HR, 1.910 [CI, 1.642 to 2.222]).
      Hazard ratios associated with sedentary time and outcomes were generally more
      pronounced at lower levels of physical activity than at higher levels.
      LIMITATION: There was marked heterogeneity in research designs and the assessment
      of sedentary time and physical activity. CONCLUSION: Prolonged sedentary time was
      independently associated with deleterious health outcomes regardless of physical
      activity. PRIMARY FUNDING SOURCE: None.

PMID- 25599351
TI  - Celebrating the ACP centennial: from the annals archive.

PMID- 25599352
TI  - Too much sitting and chronic disease risk: steps to move the science forward.

PMID- 25599353
TI  - Vasodilator-responsive idiopathic pulmonary arterial hypertension: evidence for a
      new disease?

PMID- 25599354
TI  - The greatest casualty is being forgotten.

PMID- 25599355
TI  - Kaleidoscope.

PMID- 25599356
TI  - Acute vasodilator responsiveness and microvascular recruitment in idiopathic
      pulmonary arterial hypertension.

PMID- 25599358
TI  - Review: assessment of lower urinary tract symptoms did not detect bladder outlet
      obstruction in men.

PMID- 25599359
TI  - Incident perioperative AF increased risk for ischemic stroke at 1 year, with
      greater risk after noncardiac surgery.

PMID- 25599357
TI  - Web Exclusives. The consult guys--too close for comfort? For how long must I stop
      this anticoagulant for an epidural?

PMID- 25599360
TI  - Patients with polymyalgia rheumatica had a 2.6-fold increased risk for vascular
      events at a median 7.8 y.

PMID- 25599361
TI  - Compared with unilateral TKA, simultaneous bilateral TKA was linked to in
      hospital mortality.

PMID- 25599362
TI  - In older adults, high- vs standard-dose influenza vaccine reduced laboratory
      confirmed influenza.

PMID- 25599363
TI  - Pooled RCTs: alteplase within 4.5 hours of ischemic stroke improves the
      likelihood of good outcome.

PMID- 25599364
TI  - In suspected nephrolithiasis, US did not differ from CT for high-risk diagnoses
      but reduced radiation exposure.

PMID- 25599365
TI  - Bisphosphonates do not reduce breast cancer in postmenopausal women.

PMID- 25599366
TI  - Review: in type 2 diabetes, GLP-1 agonists plus basal insulin reduce HbA1c
      without increasing hypoglycemia.

PMID- 25599367
TI  - In hypertension with high CV risk, BP self-monitoring and medication self
      titration reduced BP at 12 months.

PMID- 25599368
TI  - Review: in high-risk ulcers, intermittent and continuous PPI therapy do not
      differ for recurrent bleeding.

PMID- 25599369
TI  - In critical illness, high-protein enteral nutrition with immune-modulating
      nutrients did not reduce infections.

PMID- 25599370
TI  - Improved photocatalytic activity in RuO2-ZnO nanoparticulate heterostructures due
      to inhomogeneous space charge effects.
AB  - New 2-6 wt% RuO2-ZnO heterojunction nanocatalysts were synthesized by a
      straightforward two-step procedure. They were composed of a porous network of
      aggregated 25 nm wurtzite ZnO nanocrystallites modified with RuO2 and showed
      enhanced light absorption in the visible region due to surface plasmon resonance.
      In order to investigate the energetic structure of the photocatalyst XPS core
      line and valence band spectra of in situ in UHV prepared heterointerfaces were
      compared to results obtained from the particles. The shift of Zn 2p3/2 and O 1s
      core level spectra was determined to be at least 0.80 +/- 0.05 eV for the in situ
      prepared heterojunction whereas it was found to be 0.40 +/- 0.05 and 0.45 +/-
      0.05 eV, respectively, in the photocatalysts. The different values were ascribed
      to the reduced size of the particles and the different measurability of band
      bending at the interface of the heterojunction RuO2-ZnO compared to the
      nanoparticles. The RuO2/ZnO photocatalysts showed higher photocatalytic activity
      and recyclability than pure ZnO for the degradation of various dyes under UV
      light irradiation due to vectorial charge separation of photogenerated electrons
      and holes resulting from internal electric field, the ruthenium oxide acting as a
      quasi-metallic contact. 

PMID- 25599371
TI  - A word of caution regarding proposed benefits of albumin from ALBIOS: a dose of
      healthy skepticism.

PMID- 25599372
TI  - Prevalence of and trends in dyslipidemia and blood pressure among US children and
      adolescents, 1999-2012.
AB  - IMPORTANCE: Recent national data suggest there were improvements in serum lipid
      concentrations among US children and adolescents between 1988 and 2010 but an
      increase in or stable blood pressure (BP) during a similar period. OBJECTIVE: To
      describe the prevalence of and trends in dyslipidemia and adverse BP among US
      children and adolescents. DESIGN: The National Health and Nutrition Examination
      Survey, a cross-sectional survey. SETTING: Noninstitutionalized US population.
      PARTICIPANTS: Children and adolescents aged 8 to 17 years with measured lipid
      concentrations (n = 1482) and BP (n = 1665). MAIN OUTCOMES AND MEASURES: Adverse
      concentrations of total cholesterol (TC) (>= 200 mg/dL), high-density lipoprotein
      cholesterol (HDL-C) (<40 mg/dL), and non-HDL-C (>= 145 mg/dL) (to convert TC, HDL
      C, and non-HDL-C to millimoles per liter, multiply by 0.0259) and high or
      borderline BP were examined. Definitions of BP were informed by the Fourth Report
      on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children
      and Adolescents by the National High Blood Pressure Education Program Working
      Group on High Blood Pressure in Children and Adolescents. Analyses of linear
      trends in dyslipidemias and BP were conducted overall and separately by sex
      across 7 periods (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, 2009
      2010, and 2011-2012). RESULTS: In 2011-2012, 20.2% (95% CI, 16.3-24.6) of youths
      had an adverse concentration of TC, HDL-C, or non-HDL-C and 11.0% (95% CI, 8.8
      13.4) had either high or borderline BP. The prevalences of adverse concentrations
      decreased between 1999-2000 and 2011-2012 for TC (10.6% [95% CI, 8.3-13.2] vs
      7.8% [95% CI, 5.7-10.4]; P = .006), HDL-C (17.9% [95% CI, 15.0-21.0] vs 12.8%
      [95% CI, 9.8-16.2]; P = .003), and non-HDL-C (13.6% [95% CI, 11.3-16.2] vs 8.4%
      [95% CI, 5.9-11.5]; P < .001). There was a decrease in high BP between 1999-2000
      (3.0% [95% CI, 2.0-4.3]) and 2011-2012 (1.6% [95% CI, 1.0-2.4]) (P = .003). There
      was no change from 1999-2000 to 2011-2012 in borderline high BP (7.6% [95% CI,
      5.8-9.8] vs 9.4% [95% CI, 7.2-11.9]; P = .90) or either high or borderline high
      BP (10.6% [8.4-13.1] vs 11.0% [95% CI, 8.8-13.4]; P = .26). CONCLUSIONS AND
      RELEVANCE: In 2011-2012, approximately 1 in 5 children and adolescents aged 8 to
      17 years had an adverse lipid concentration of TC, HDL-C, or non-HDL-C and
      slightly more than 1 in 10 had either borderline high or high BP. The prevalence
      of dyslipidemia modestly decreased between 1999-2000 and 2011-2012, but either
      high or borderline high BP remained stable. The reasons for these trends require
      further study.

PMID- 25599373
TI  - Cluster of human infections with avian influenza A (H7N9) cases: a temporal and
      spatial analysis.
AB  - OBJECTIVES: This study aims to describe the spatial and temporal characteristics
      of human infections with H7N9 virus in China using data from February 2013 to
      March 2014 from the websites of every province's Population and Family Planning
      Commission. METHODS: A human infection with H7N9 virus dataset was summarized by
      county to analyze its spatial clustering, and by date of illness onset to analyze
      its space-time clustering using the ESRI(r) Geographic Information System (GIS)
      software ArcMapTM 10.1 and SatScan. RESULTS: Based on active surveillance data,
      the distribution map of H7N9 cases shows that compared to the rest of China, the
      areas from near the Yangtze River delta (YRD) to farther south around the Pearl
      River delta (PRD) had the highest densities of H7N9 cases. The case data shows a
      strong space-time clustering in the areas on and near the YRD from 26 March to 18
      April 2013 and a weak space-time clustering only in the areas on and near the PRD
      between 3 and 4 February 2014. However, for the rest of the study period, H7N9
      cases were spatial-temporally randomly distributed. CONCLUSIONS: Our results
      suggested that the spatial-temporal clustering of H7N9 in China between 2013 and
      2014 is fundamentally different.

PMID- 25599374
TI  - Gender differences in recreational sports participation among Taiwanese adults.
AB  - This study examines the gender differences in the enjoyment of recreational
      sports participation among Taiwanese adults. Data were obtained using the 2007
      Taiwan Social Change Survey. The questionnaire included a topical module of the
      International Social Survey Program regarding leisure time and sports. Results
      showed that male subjects were more likely to participate in recreational sports
      to improve their appearance and on account of their personal interest. In
      addition to these factors, female subjects also experienced greater motivation to
      participate when Taiwanese athletes performed well in international sporting
      competitions. This study confirmed that the factors influencing enjoyment of
      recreational sports participation differ among men and women. These results can
      be used to better inform public health professionals and other regulatory
      organizations formulating physical activity intervention strategies. 

PMID- 25599376
TI  - Classifying dynamic contact line modes in drying drops.
AB  - Although the evaporation mode of sessile droplets is almost universally
      characterized as either constant contact radius (CCR) or constant contact angle
      (CCA), here we investigate two alternatives where the contact line speed is
      either constant or inversely proportional to the droplet radius. We present
      supporting evidence from our experiments on poly(ethylene oxide) (PEO) polymer
      solutions and blood, and from literature on pure and binary liquids, colloidal
      suspensions, soft substrates, reactive dewetting and hole nucleation. We
      introduce the use of novel "clock-drop" images to visualize droplet evolution and
      dimensionless height-radius plots to characterize the evaporative pathways.
      Combining these with a simple scaling argument, we show that receding speed is
      inversely proportional to the three-phase contact radius R, with a constant of
      proportionality A, which is dependent on the drying conditions and drop shape,
      but independent of drop volume. We have shown that this is equivalent to a linear
      decrease in contact area with time. By varying only A, which we achieved
      experimentally by choosing solutions whose precipitate constricts after
      deposition, the evaporation mode can be altered continuously to include the two
      established modes CCR and CCA, and two new modes which we term "slowly receding"
      and "rapidly receding", which are characterised by fully dried "doughnut" and
      "pillar" deposits respectively. 

PMID- 25599375
TI  - Agreement between exhaled breath carbon monoxide threshold levels and self
      reported cigarette smoking in a sample of male adolescents in Jordan.
AB  - This study aimed to measure the percent agreement between Exhaled Breath Carbon
      Monoxide (eBCO) measure using a piCO+ smokerlyzer(r) and self-reported cigarette
      smoking status and to determine the optimal thresholds for definite
      identification of cigarette smokers of male school students in Jordan. A
      descriptive, cross sectional, study of a random sample of male adolescents in
      grades 7 and 8 from four public high schools in Irbid, completed an adaptation of
      a standardized Arabic-language tobacco smoking questionnaire and an eBCO measure.
      Sensitivity and specificity of the eBCO were calculated against self-reported
      cigarette smoking. Participants (n = 439) had a mean age of 12.5 years (SD =
      0.50) and 174 (39.9%) reported being an ever smoker of whom 59 (33.9%) reported
      being a recent (30-day) smoker. The optimal eBCO cut-off point for recent smoking
      was 4.5 ppm with a sensitivity of 84.7% and specificity of 65.5%. Overall, eBCO
      can accurately identify recent smokers and distinguish them from non-smokers. The
      eBCO use enables healthcare professionals and researchers to assess efficacy of
      smoking cessation and prevention programs without necessarily relying on self
      report. Further research is indicated to validate our findings and should be
      expanded to include females, detailed characteristics of cigarette and waterpipe
      smoking. 

PMID- 25599378
TI  - The Efficacy of a Walking Intervention Using Social Media to Increase Physical
      Activity: A Randomized Trial.
AB  - BACKGROUND: Facebook may be a useful tool to provide a social support group to
      encourage increases in physical activity. This study examines the efficacy of a
      Facebook social support group to increase steps/day in young women. METHODS:
      Female college freshmen (N = 63) were randomized to one of two 8-week
      interventions: a Facebook Social Support Group (n = 32) or a Standard Walking
      Intervention (n = 31). Participants in both groups received weekly step goals and
      tracked steps/day with a pedometer. Women in the Facebook Social Support Group
      were also enrolled in a Facebook group and asked to post information about their
      steps/day and provide feedback to one another. RESULTS: Women in both
      intervention arms significantly increased steps/day pre- to postintervention
      (F(8,425) = 94.43, P < .001). However, women in the Facebook Social Support Group
      increased steps/day significantly more (F(1,138) = 11.34, P < .001) than women in
      the Standard Walking Intervention, going from 5295 to 12,472 steps/day.
      CONCLUSIONS: These results demonstrate the potential effectiveness of using
      Facebook to offer a social support group to increase physical activity in young
      women. Women in the Facebook Social Support Group increased walking by
      approximately 1.5 miles/day more than women in the Standard Walking Intervention
      which, if maintained, could have a profound impact on their future health.

PMID- 25599377
TI  - Modeling the Declining Positivity Rates for Human Immunodeficiency Virus Testing
      in New York State.
AB  - OBJECTIVE: New York health care providers have experienced declining percentages
      of positive human immunodeficiency virus (HIV) tests among patients. Furthermore,
      observed positivity rates are lower than expected on the basis of the national
      estimate that one-fifth of HIV-infected residents are unaware of their infection.
      We used mathematical modeling to evaluate whether this decline could be a result
      of declining numbers of HIV-infected persons who are unaware of their infection,
      a measure that is impossible to measure directly. DESIGN AND SETTING: A stock-and
      flow mathematical model of HIV incidence, testing, and diagnosis was developed.
      The model includes stocks for uninfected, infected and unaware (in 4 disease
      stages), and diagnosed individuals. Inputs came from published literature and
      time series (2006-2009) for estimated new infections, newly diagnosed HIV cases,
      living diagnosed cases, mortality, and diagnosis rates in New York. MAIN OUTCOME
      MEASURES: Primary model outcomes were the percentage of HIV-infected persons
      unaware of their infection and the percentage of HIV tests with a positive result
      (HIV positivity rate). RESULTS: In the base case, the estimated percentage of
      unaware HIV-infected persons declined from 14.2% in 2006 (range, 11.9%-16.5%) to
      11.8% in 2010 (range, 9.9%-13.1%). The HIV positivity rate, assuming testing
      occurred independent of risk, was 0.12% in 2006 (range, 0.11%-0.15%) and 0.11% in
      2010 (range, 0.10%-0.13%). The observed HIV positivity rate was more than 4 times
      the expected positivity rate based on the model. CONCLUSIONS: HIV test positivity
      is a readily available indicator, but it cannot distinguish causes of underlying
      changes. Findings suggest that the percentage of unaware HIV-infected New Yorkers
      is lower than the national estimate and that the observed HIV test positivity
      rate is greater than expected if infected and uninfected individuals tested at
      the same rate, indicating that testing efforts are appropriately targeting
      undiagnosed cases.

PMID- 25599380
TI  - The first documented controlled trial in history.
AB  - The first reported controlled human trial was conducted 2500 years ago by the
      Biblical judge Gideon Ben Yoash, who challenged God's Angel: "I will put a fleece
      of wool on the threshing floor. If there is dew on the fleece only, and it is dry
      on all the ground, then I will know that Thou wilt deliver Israel through me, as
      Thou hast spoken". In the control part of the trial he asked the Angel to keep
      the wool dry while the ground around it will be soaked with morning dew. It is
      unfortunate that these principles were not practiced for thousands of years
      thereafter, as many medical challenges could have been solved earlier.   

PMID- 25599379
TI  - Cytology of endoscopically obtained biopsies for the diagnosis of chronic
      intestinal diseases in cats.
AB  - OBJECTIVE: To evaluate the diagnostic value of cytology of endoscopically
      obtained biopsies in cats presented for chronic gastrointestinal complaints with
      emphasis on the diagnosis of low-grade alimentary lymphoma (LGAL). MATERIALS AND
      METHODS: Data of endoscopically obtained duodenal biopsies from 137 cats were
      evaluated retrospectively. Cytology was performed using the squash smear
      technique with subsequent Diff Quick(r) staining. Pathological findings were
      categorized according to type and grade of the inflammatory infiltrate. Moreover,
      reports were reviewed with regard to diagnosis of LGAL. Histopathology reports
      were analysed correspondingly and compared to cytology results. Histopathological
      samples were further evaluated by immunohistochemistry (IHC) if a diagnosis of
      LGAL had been expressed. RESULTS: Squash smear preparation of intestinal biopsies
      was adequate for cytological examination in >97% of cases. Using histopathology
      as gold standard, with cytology, a sensitivity and specificity for detection of a
      pathologic process in feline intestinal biopsies of 68.1% and 70.6% were
      calculated, respectively. Regarding the detection of lymphoplasmacytic (LPE) and
      eosinophilic enteritis a statistically significant correlation with
      histopathology (p<0.05) was observed. With regard to grade of the inflammatory
      infiltrate, a weak correlation was calculated (r=0.482). Of 21 cats diagnosed or
      suspected with LGAL by cytology, IHC confirmed nine cases whereas 11 cases were
      reclassified as LPE. None of the confirmed LGAL had been missed with
      histopathology. A sensitivity of 60.0% and specificity of 90.6% for cytological
      detection of feline LGAL was obtained. CONCLUSION AND CLINICAL RELEVANCE: The
      sensitivity of cytology to diagnose LGAL is low and it has no additional
      significance to histological biopsies.

PMID- 25599381
TI  - Wing-pitching mechanism of hovering Ruby-throated hummingbirds.
AB  - In hovering flight, hummingbirds reverse the angle of attack of their wings
      through pitch reversal in order to generate aerodynamic lift during both
      downstroke and upstroke. In addition, the wings may pitch during translation to
      further enhance lift production. It is not yet clear whether these pitching
      motions are caused by the wing inertia or actuated through the musculoskeletal
      system. Here we perform a computational analysis of the pitching dynamics by
      incorporating the realistic wing kinematics to determine the inertial effects.
      The aerodynamic effect is also included using the pressure data from a previous
      three-dimensional computational fluid dynamics simulation of a hovering
      hummingbird. The results show that like many insects, pitch reversal of the
      hummingbird is, to a large degree, caused by the wing inertia. However, actuation
      power input at the root is needed in the beginning of pronation to initiate a
      fast pitch reversal and also in mid-downstroke to enable a nose-up pitching
      motion for lift enhancement. The muscles on the wing may not necessarily be
      activated for pitching of the distal section. Finally, power analysis of the
      flapping motion shows that there is no requirement for substantial elastic energy
      storage or energy absorption at the shoulder joint. 

PMID- 25599382
TI  - Acute stress disorder modifies cerebral activity of amygdala and prefrontal
      cortex.
AB  - The diagnosis constraint of acute stress disorder (ASD), consisting of testing
      individuals in the month following trauma exposure, limits research on the very
      early and initial stage of the disease. In this regard, this work aims to explore
      the cerebral mechanism of ASD in a population of fire-fighters before and after
      trauma exposure. Thirty-six healthy non-traumatized male fire-fighters were
      explored by an fMRI emotional face-matching task to evaluate the cerebral
      substrate of emotional recognition. During the two years of the follow-up, two
      subjects were traumatized, and thus retested, as were 10 non-traumatized subjects
      among the initial non-exposed ones. In comparison to non-exposed subjects, fire
      fighters with ASD had enhanced amygdala, orbitofrontal, and dorsolateral
      prefrontal BOLD responses to fearful and angry faces (p < .05, FDR-corrected).
      These results shed new light on the cerebral mechanism associated with ASD. We
      observed for the first time the existence of an altered fear processing pathway
      in ASD that is mediated by amygdala and prefrontal cortex hyperactivity, which
      might be at the core of the disorder.

PMID- 25599383
TI  - Fluorescence quenching in oligonucleotides containing 7-substituted 7
      deazaguanine bases prepared by the nicking enzyme amplification reaction.
AB  - Recently, we reported the use of the Nicking Enzyme Amplification Reaction (NEAR)
      for the enzymatic synthesis of short oligonucleotides (ONs) containing 5
      substituted pyrimidine or 7-substituted 7-deazaadenine nucleotides. Since no
      oligonucleotide products were visible on agarose gels stained by an intercalating
      dye (GelRed), we assumed that the method did not work for 7-substituted 7
      deazaguanine deoxyribonucleoside triphosphates. We revisited the work and found
      that the NEAR method works for 7-deazaguanine nucleotides as well but that the
      resulting modified ONs quench the fluorescence of DNA intercalators, rendering
      them invisible on gel electrophoresis stained by them. Here, we report on the
      modified methodology for the NEAR synthesis and analysis of G-modified ONs and on
      quantification of the fluorescence quenching. 

PMID- 25599384
TI  - SLC25A24 as a novel susceptibility gene for low fat mass in humans and mice.
AB  - CONTEXT: Genetic factors contribute to the development of obesity. OBJECTIVE: The
      aim of this study was to identify novel genes that regulate body fat mass.
      DESIGN: We performed a search for single nucleotide polymorphisms (SNPs)
      associated with body fat percentage using SNP arrays and undertook a replication
      study and animal study. SETTING AND PATIENTS: Baseline examinations were
      conducted in 251 (first-stage analysis), 499 (second-stage analysis), and 732
      (additional analyses) Japanese postmenopausal women. The mean age (mean +/- SD)
      of the subjects was 66.5 +/- 9.4 years. We also analyzed the fat-related
      phenotypes of a candidate gene in knockout mice. RESULTS: In the analysis of
      total body fat, we focused on an SNP of SLC25A24 that showed the lowest
      significant P value obtained from multiple comparison tests among Japanese
      postmenopausal women. A significant association was also found between SLC25A24
      SNPs and body mass index in the 1482 Japanese postmenopausal women examined in
      the study. The SLC25A24 SNPs affected the mRNA expression of SLC25A24 in human
      preadipocytes. Compared with wild-type mice, Slc25a24-KO mice had significantly
      lower body weights and white adipose tissue weights. Adipocyte differentiation
      was inhibited in Slc25a24-KO adipose tissues and Slc25a24-knockdown adipocytes.
      CONCLUSIONS: Genetic analyses in human and mouse models revealed the importance
      of SLC25A24/Slc25a24 in the regulation of body fat mass and adipogenesis.

PMID- 25599386
TI  - Mast cell hyperplasia is associated with aldosterone hypersecretion in a subset
      of aldosterone-producing adenomas.
AB  - CONTEXT: Adrenal mast cells can stimulate aldosterone secretion through the local
      release of serotonin (5-HT) and activation of the 5-HT4 receptor (5-HT4). In
      aldosterone-producing adenomas (APAs), 5-HT4 receptor is overexpressed and the
      administration of 5-HT4 receptor agonists to patients with APA increases plasma
      aldosterone levels. These data and the well-documented role of mast cells in
      tumorigenesis suggest that mast cells may be involved in the pathophysiology of
      APA. OBJECTIVE: The study aimed at investigating the occurrence of mast cells in
      a series of APA tissues and to examine the influence of mast cells on aldosterone
      secretion. DESIGN: The occurrence of mast cells in APAs was investigated by
      immunohistochemistry. Mast cell densities were compared with clinical data. The
      influence of mast cells on aldosterone production was studied by using cultures
      of human mast cell and adrenocortical cell lines. RESULTS: In APA tissues, the
      density of mast cells was found to be increased in comparison with normal
      adrenals. Mast cells were primarily observed in adrenal cortex adjacent to
      adenomas or in the adenomas themselves, distinguishing two groups of APAs. A
      subset of adenomas was found to contain a high density of intratumoral mast
      cells, which was correlated with aldosterone synthase expression and in vivo
      aldosterone secretory parameters. Administration of conditioned medium from
      cultures of human mast cell lines to human adrenocortical cells induced a
      significant increase in aldosterone synthase (CYP11B2) mRNA expression and
      aldosterone production. CONCLUSION: APA tissues commonly contain numerous mast
      cells that may influence aldosterone secretion through the local release of
      regulatory factors.

PMID- 25599385
TI  - Combined training enhances skeletal muscle mitochondrial oxidative capacity
      independent of age.
AB  - CONTEXT: Skeletal muscle from sedentary older adults exhibits reduced
      mitochondrial abundance and oxidative capacity. OBJECTIVE: The primary objective
      was to determine whether 8 weeks of combined training (CT) has a more robust
      effect than endurance training (ET) or resistance training (RT) on mitochondrial
      physiology in healthy young (18-30 years) and older (>= 65 years) adults.
      INTERVENTION: Thirty-four young and 31 older adults were randomly assigned to 8
      weeks of ET, RT, and control/CT. Control subjects completed 8 weeks of no
      exercise (control) followed by 8 weeks of CT. Body composition, skeletal muscle
      strength, and peak oxygen uptake were measured before and after the intervention.
      Vastus lateralis muscle biopsy samples were obtained before and 48 hours after
      the intervention. Mitochondrial physiology was evaluated by high-resolution
      respirometry and expression of mitochondrial proteins and transcription factors
      by quantitative PCR and immunoblotting. RESULTS: ET and CT significantly
      increased oxidative capacity and expression of mitochondrial proteins and
      transcription factors. All training modalities improved body composition,
      cardiorespiratory fitness, and skeletal muscle strength. CT induced the most
      robust improvements in mitochondria-related outcomes and physical characteristics
      despite lower training volumes for the ET and RT components. Importantly, most of
      the adaptations to training occurred independent of age. CONCLUSION:
      Collectively, these results demonstrate that both ET and CT increase muscle
      mitochondrial abundance and capacity although CT induced the most robust
      improvements in the outcomes measured. In conclusion, CT provides a robust
      exercise regimen to improve muscle mitochondrial outcomes and physical
      characteristics independent of age.

PMID- 25599387
TI  - Discovery of coding genetic variants influencing diabetes-related serum
      biomarkers and their impact on risk of type 2 diabetes.
AB  - CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of
      its pathophysiological signatures is crucial for a better understanding and
      treatment of the disease. OBJECTIVE: We aimed to discover underlying coding
      genetic variants influencing fasting serum levels of nine biomarkers associated
      with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein
      1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-alpha,
      and leptin. DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult
      Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were
      tested for association with each biomarker. Identified loci were tested for
      association with T2D through a large-scale meta-analysis involving up to 17 024
      T2D cases and up to 64 186 controls. RESULTS: We discovered 11 associations
      between single-nucleotide polymorphisms and five distinct biomarkers at a study
      wide P < 3.4 * 10(-7). Nine associations were novel: IL18: BIRC6, RAD17,
      MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and
      heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A,
      and GCKR) were significantly associated with T2D, of which the association with
      the CELSR2 locus has not been shown previously. CONCLUSION: The identified loci
      influence processes related to insulin signaling, cell communication, immune
      function, apoptosis, DNA repair, and oxidative stress, all of which could provide
      a rationale for novel diabetes therapeutic strategies.

PMID- 25599388
TI  - Iron deficiency, an independent risk factor for isolated hypothyroxinemia in
      pregnant and nonpregnant women of childbearing age in China.
AB  - CONTEXT: Isolated hypothyroxinemia during early pregnancy may irreversibly damage
      the neurodevelopment of offspring. However, the causes are not well clarified.
      OBJECTIVE: To explore the association of iron deficiency (ID) with hypothyroid
      function of women in early pregnancy and nonpregnant women. DESIGN: A total of
      7953 pregnant women of <= 12 weeks gestation and 2000 childbearing-aged women
      were recruited. A subpopulation including 3340 pregnant women and 1052
      nonpregnant women with sufficient iodine intake and negative thyroid peroxidase
      antibody were studied. Mild and severe cases of hypothyroxinemia were defined as
      free T4 levels below the 10th percentile and the 5th percentile, respectively,
      with normal TSH. Total body iron, serum ferritin, and serum transferrin receptor
      were used as indicators for iron nutrition. RESULTS: Serum free T4 levels were
      significantly lower in both pregnant and nonpregnant women with ID compared with
      the corresponding groups without ID (both P < .05). The prevalence of mild and
      severe hypothyroxinemia was markedly higher in women with ID than those without,
      in both pregnant and nonpregnant women (all P < .01). Logistic regression
      indicated that ID was an independent risk factor for both mild and severe
      hypothyroxinemia in pregnancy (odds ratio [OR] = 2.440, 95% confidence interval
      [CI]: 1.324-4.496, P = .004; and OR = 3.278, 95% CI: 1.443-7.446, P = .005,
      respectively) and nonpregnancy (OR = 2.662, 95% CI: 1.330-5.329, P = .006; and OR
      = 3.254, 95% CI: 1.375-7.700, P = .007, respectively). CONCLUSIONS: An
      association between ID and isolated hypothyroxinemia was found in both pregnant
      and nonpregnant childbearing-aged women, independent of the effects of iodine and
      thyroid autoimmunity. We speculate that ID may be a pathogenic factor for
      hypothyroxinemia, even in pregnant women during the first trimester.

PMID- 25599389
TI  - The Effect of the Social and Physical Environment on Children's Independent
      Mobility to Neighborhood Destinations.
AB  - BACKGROUND: Relationships between context-specific measures of the physical and
      social environment and children's independent mobility to neighborhood
      destination types were examined. METHODS: Parents in RESIDE's fourth survey
      reported whether their child (8-15 years; n = 181) was allowed to travel without
      an adult to school, friend's house, park and local shop. Objective physical
      environment measures were matched to each of these destinations. Social
      environment measures included neighborhood perceptions and items specific to
      local independent mobility. RESULTS: Independent mobility to local destinations
      ranged from 30% to 48%. Independent mobility to a local park was less likely as
      the distance to the closest park (small and large size) increased and less likely
      with additional school grounds (P < .05). Independent mobility to school was less
      likely as the distance to the closest large park increased and if the
      neighborhood was perceived as unsafe (P < .05). Independent mobility to a park or
      shops decreased if parenting social norms were unsupportive of children's local
      independent movement (P < .05). CONCLUSIONS: Independent mobility appears
      dependent upon the specific destination being visited and the impact of
      neighborhood features varies according to the destination examined. Findings
      highlight the importance of access to different types and sizes of urban green
      space for children's independent mobility to parks.

PMID- 25599390
TI  - Lineage specificity of primary cilia in the mouse embryo.
AB  - Primary cilia are required for vertebrate cells to respond to specific
      intercellular signals. Here we define when and where primary cilia appear in the
      mouse embryo using a transgenic line that expresses ARL13B-mCherry in cilia and
      Centrin 2-GFP in centrosomes. Primary cilia first appear on cells of the epiblast
      at E6.0 and are subsequently present on all derivatives of the epiblast. In
      contrast, extraembryonic cells of the visceral endoderm and trophectoderm
      lineages have centrosomes but no cilia. Stem cell lines derived from embryonic
      lineages recapitulate the in vivo pattern: epiblast stem cells are ciliated,
      whereas trophoblast stem cells and extraembryonic endoderm (XEN) stem cells lack
      cilia. Basal bodies in XEN cells are mature and can form cilia when the AURKA
      HDAC6 cilium disassembly pathway is inhibited. The lineage-dependent distribution
      of cilia is stable throughout much of gestation, defining which cells in the
      placenta and yolk sac are able to respond to Hedgehog ligands.

PMID- 25599393
TI  - The Kindler syndrome: a spectrum of FERMT1 mutations in Iranian families.

PMID- 25599391
TI  - Helichrysum and Grapefruit Extracts Boost Weight Loss in Overweight Rats Reducing
      Inflammation.
AB  - Obesity is characterized by an increased production of inflammatory markers. High
      levels of circulating free fatty acids and chronic inflammation lead to increased
      oxidative stress, contributing to the development of insulin resistance (IR).
      Recent studies have focused on the potential use of flavonoids for obesity
      management due to their antioxidant and anti-inflammatory properties. This study
      was designed to investigate the antioxidant and anti-inflammatory effects of
      helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty
      eight male Wistar rats were randomly distributed in two groups: control group
      (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water
      and food access, the rats fed HFS diet changed to standard diet and were
      reassigned into three groups (n=10 each group): nonsupplemented, helichrysum
      extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks.
      Rats supplemented with both extracts gained less body weight during the 5-week
      period of treatment, showed lower serum insulin levels and liver TBARS levels.
      Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract
      administered groups. These results were accompanied by a reduction in TNFalpha
      gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2
      expression in intestinal mucosa. Helichrysum and grapefruit extracts might be
      used as complement hypocaloric diets in weight loss treatment. Both extracts
      helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation
      markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant
      rats. 

PMID- 25599395
TI  - MMP-1 and -3 promoter variants are indicative of a common susceptibility for skin
      and lung aging: results from a cohort of elderly women (SALIA).
AB  - Studies have indicated that there may be a smoking-dependent association between
      skin wrinkling and airflow obstruction of the lung. It was suggested that this
      association might be because of an underlying susceptibility in genes responsible
      for extracellular matrix (ECM) remodeling. Our purpose was to confirm the
      association between skin wrinkling and airflow obstruction and to identify
      genetic polymorphisms indicative of an underlying susceptibility. In 697 elderly
      women, we assessed skin wrinkles by SCINEXA (SCore for INtrinsic and EXtrinsic
      skin Aging) and airflow obstruction by spirometry, using the ratio of forced
      expiratory volume in 1 second (FEV1) to forced volume capacity (FVC). For
      association analysis, we used multiple regression and found that the FEV1/FVC
      ratio decreased 1.2% per 6-point increase in the wrinkle severity score after
      accounting for age, education, body mass index, skin type, and sun exposure. This
      association was significant and independent of smoking or air pollution. Most
      interestingly, this association occurred only in carriers of the matrix
      metalloproteinase-1 (MMP-1) 2G (rs1799750) or the MMP-3 6A (rs3025058) allele but
      not in homozygous carriers of the 1G or 5A allele. Thus, skin and lung aging are
      linked in carriers of the 2G or 6A allele. These alleles appear to be indicative
      of a common genetic susceptibility. 

PMID- 25599394
TI  - Psoriasis and cardiometabolic traits: modest association but distinct genetic
      architectures.
AB  - Psoriasis has been linked to cardiometabolic diseases, but epidemiological
      findings are inconsistent. We investigated the association between psoriasis and
      cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a
      prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A
      potential genetic overlap was explored using genome-wide data from >22,000
      coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping
      study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls.
      After controlling for major confounders, in the cross-sectional analysis
      psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds
      ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction
      (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly
      increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95%
      CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in
      systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D
      and MI per 10,000 person-years. Except for weak signals from within the major
      histocompatibility complex, there was no evidence of genetic risk loci shared
      between psoriasis and cardiometabolic traits. Our findings suggest that
      psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and
      that the genetic architecture of psoriasis and cardiometabolic traits is largely
      distinct. 

PMID- 25599396
TI  - The RNA helicase Aquarius exhibits structural adaptations mediating its
      recruitment to spliceosomes.
AB  - Aquarius is a multifunctional putative RNA helicase that binds precursor-mRNA
      introns at a defined position. Here we report the crystal structure of human
      Aquarius, revealing a central RNA helicase core and several unique accessory
      domains, including an ARM-repeat domain. We show that Aquarius is integrated into
      spliceosomes as part of a pentameric intron-binding complex (IBC) that, together
      with the ARM domain, cross-links to U2 snRNP proteins within activated
      spliceosomes; this suggests that the latter aid in positioning Aquarius on the
      intron. Aquarius's ARM domain is essential for IBC formation, thus indicating
      that it has a key protein-protein-scaffolding role. Finally, we provide evidence
      that Aquarius is required for efficient precursor-mRNA splicing in vitro. Our
      findings highlight the remarkable structural adaptations of a helicase to achieve
      position-specific recruitment to a ribonucleoprotein complex and reveal a new
      building block of the human spliceosome. 

PMID- 25599397
TI  - Toll-like receptor 8 senses degradation products of single-stranded RNA.
AB  - Toll-like receptor 8 (TLR8) recognizes viral or bacterial single-stranded RNA
      (ssRNA) and activates innate immune systems. TLR8 is activated by uridine- and
      guanosine-rich ssRNA as well as by certain synthetic chemicals; however, the
      molecular basis for ssRNA recognition has remained unknown. In this study, to
      elucidate the recognition mechanism of ssRNA, we determined the crystal
      structures of human TLR8 in complex with ssRNA. TLR8 recognized two degradation
      products of ssRNA-uridine and a short oligonucleotide-at two distinct sites:
      uridine bound the site on the dimerization interface where small chemical ligands
      are recognized, whereas short oligonucleotides bound a newly identified site on
      the concave surface of the TLR8 horseshoe structure. Site-directed mutagenesis
      revealed that both binding sites were essential for activation of TLR8 by ssRNA.
      These results demonstrate that TLR8 is a sensor for both uridine and a short
      oligonucleotide derived from RNA.

PMID- 25599399
TI  - Effect of some essential oils on phagocytosis and complement system activity.
AB  - The aim of the present study was to investigate the in vitro activity of 15
      essential oils, 4 essential oil fractions, and 3 pure compounds (thymol,
      carvacrol, and eugenol) on phagocytosis by human neutrophils and on complement
      system. Samples were characterized by GC and GC-MS. Most of the oils (nutmeg,
      clove, niaouli, tea tree, bay laurel, lemon, red thyme, ginger), nutmeg terpenes,
      eugenol, and carvacrol showed mild to moderate inhibition of phagocytosis (25-40%
      inhibition at doses ranging from 40 to 60 MUg/mL); highest inhibitory activity
      was found for thymol (72% at 56 MUg/mL), whereas the mixture of bornyl and
      isobornyl acetates showed a mild stimulating activity (21% at 56 MUg/mL). All
      samples were inactive in the alternative pathway of complement system, whereas on
      classical pathway, clove oil, eugenol, palmarosa oil, red thyme oil, tarragon
      oil, and carvacrol showed the highest activity, with IC50 values ranging from 65
      to 78 MUg/mL.

PMID- 25599398
TI  - Ring closure activates yeast gammaTuRC for species-specific microtubule
      nucleation.
AB  - The gamma-tubulin ring complex (gammaTuRC) is the primary microtubule nucleator
      in cells. gammaTuRC is assembled from repeating gamma-tubulin small complex
      (gammaTuSC) subunits and is thought to function as a template by presenting a
      gamma-tubulin ring that mimics microtubule geometry. However, a previous yeast
      gammaTuRC structure showed gammaTuSC in an open conformation that prevents
      matching to microtubule symmetry. By contrast, we show here that gamma-tubulin
      complexes are in a closed conformation when attached to microtubules. To confirm
      the functional importance of the closed gammaTuSC ring, we trapped the closed
      state and determined its structure, showing that the gamma-tubulin ring precisely
      matches microtubule symmetry and providing detailed insight into gammaTuRC
      architecture. Importantly, the closed state is a stronger nucleator, thus
      suggesting that this conformational switch may allosterically control gammaTuRC
      activity. Finally, we demonstrate that gammaTuRCs have a strong preference for
      tubulin from the same species.

PMID- 25599400
TI  - Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing
      lineage.
AB  - Mycobacterium tuberculosis strains of the Beijing lineage are globally
      distributed and are associated with the massive spread of multidrug-resistant
      (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical
      structure and evolutionary history of this lineage by genetic analysis of 4,987
      isolates from 99 countries and whole-genome sequencing of 110 representative
      isolates. We show that this lineage initially originated in the Far East, from
      where it radiated worldwide in several waves. We detected successive increases in
      population size for this pathogen over the last 200 years, practically coinciding
      with the Industrial Revolution, the First World War and HIV epidemics. Two MDR
      clones of this lineage started to spread throughout central Asia and Russia
      concomitantly with the collapse of the public health system in the former Soviet
      Union. Mutations identified in genes putatively under positive selection and
      associated with virulence might have favored the expansion of the most successful
      branches of the lineage. 

PMID- 25599404
TI  - The process of moving from a regionally based cervical cytology biobank to a
      national infrastructure.
AB  - This article addresses the important issue of the standardization of the biobank
      process. It reports on i) the implementation of standard operating procedures for
      the processing of liquid-based cervical cells, ii) the standardization of storage
      conditions, and iii) the ultimate establishment of nationwide standardized
      biorepositories for cervical specimens. Given the differences in the
      infrastructure and healthcare systems of various county councils in Sweden, these
      efforts were designed to develop standardized methods of biobanking across the
      nation. The standardization of cervical sample processing and biobanking is an
      important and widely acknowledged issue. Efforts to address these concerns will
      facilitate better patient care and improve research based on retrospective and
      prospective collections of patient samples and cohorts. The successful
      nationalization of the Cervical Cytology Biobank in Sweden is based on three
      vital issues: i) the flexibility of the system to adapt to other regional
      systems, ii) the development of the system based on national collaboration
      between the university and the county councils, and iii) stable governmental
      financing by the provider, the Biobanking and Molecular Resource Infrastructure
      of Sweden (BBMRI.se). We will share our experiences with biorepository
      communities to promote understanding of and advances in opportunities to
      establish a nationalized biobank which covers the healthcare of the entire
      nation. 

PMID- 25599405
TI  - Neuroticism and stress: the role of displacement behavior.
AB  - BACKGROUND AND OBJECTIVES: Neuroticism is linked with an impaired ability to cope
      with stress and is an important risk factor for stress-related disorders. Hence,
      there is interest in exploring the behavioral correlates of neuroticism and how
      such behaviors may moderate the link between neuroticism and the response to
      stress. Displacement behavior - activity such as face touching and scratching -
      is important to investigate in this respect, as recent studies indicate that such
      behavior is linked to negative emotional states and has an important stress
      coping function. Here, we explored the relationship between neuroticism,
      displacement behavior, and stress in a healthy population of men. DESIGN: This
      was a cross-sectional, quasiexperimentally controlled study. METHODS: We assessed
      participants' levels of neuroticism, and then during a Trier Social Stress Test
      quantified displacement behavior, physiological, and cognitive indices of the
      stress response; after the test we measured the self-reported experience of
      stress. RESULTS: Displacement behavior was negatively correlated with self
      reported experience, physiological, and cognitive measures of stress and
      moderated the relationships between neuroticism, self-reported experience, and
      cognitive index of stress. CONCLUSIONS: Our results suggest displacement behavior
      plays an important role in shaping the link between neuroticism and the response
      to stress.

PMID- 25599406
TI  - Calculating Electron-Transfer Coupling with Density Functional Theory: The Long
      Range-Corrected Density Functionals.
AB  - The density functional theory (DFT) with commonly used functionals is known to be
      incorrect for charge-transfer problems. With long-range-corrected (LC) density
      functionals, the asymptotic exchange potential is gradually switched to the
      Hartree-Fock exchange at a long range, and the prediction for charge-transfer
      states is greatly improved. In this work, we test LC-DFT's performance on charge
      transfer couplings. The range-separation parameter can be tuned nonempirically
      for properties of a generalized DFT. We propose to minimize the difference of
      highest-occupied Kohn-Sham orbital energy and the ionization potential (for hole
      transfer) or the lowest-unoccupied orbital energy and the electron affinity (for
      electron transfer). For photoinduced charge transfer, the minimum in the sum of
      such differences for the donor and the acceptor is proposed. With the range
      separation parameters optimized, we found that ET couplings derived from the LC
      DFT are close to those derived from coupled cluster with singles and doubles.
      When compared with experimentally derived Mulliken-Hush couplings, LC-DFT
      couplings are greatly improved as well. We also found that the couplings from BNL
      and LC-BLYP functionals are generally better than those from LC-omegaPBE and LC
      omegaPBE0. LC-DFT is suitable for calculating ET coupling, especially with this
      nonempirical approach for the range-separation parameter. 

PMID- 25599403
TI  - The landscape of long noncoding RNAs in the human transcriptome.
AB  - Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue
      physiology and disease processes including cancer. To delineate genome-wide
      lncRNA expression, we curated 7,256 RNA sequencing (RNA-seq) libraries from
      tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25
      independent studies. We applied ab initio assembly methodology to this data set,
      yielding a consensus human transcriptome of 91,013 expressed genes. Over 68%
      (58,648) of genes were classified as lncRNAs, of which 79% were previously
      unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and
      7% (3,900) overlapped disease-associated SNPs. To prioritize lineage-specific,
      disease-associated lncRNA expression, we employed non-parametric differential
      expression testing and nominated 7,942 lineage- or cancer-associated lncRNA
      genes. The lncRNA landscape characterized here may shed light on normal biology
      and cancer pathogenesis and may be valuable for future biomarker development. 

PMID- 25599402
TI  - A method for calculating probabilities of fitness consequences for point
      mutations across the human genome.
AB  - We describe a new computational method for estimating the probability that a
      point mutation at each position in a genome will influence fitness. These
      'fitness consequence' (fitCons) scores serve as evolution-based measures of
      potential genomic function. Our approach is to cluster genomic positions into
      groups exhibiting distinct 'fingerprints' on the basis of high-throughput
      functional genomic data, then to estimate a probability of fitness consequences
      for each group from associated patterns of genetic polymorphism and divergence.
      We have generated fitCons scores for three human cell types on the basis of
      public data from ENCODE. In comparison with conventional conservation scores,
      fitCons scores show considerably improved prediction power for cis regulatory
      elements. In addition, fitCons scores indicate that 4.2-7.5% of nucleotides in
      the human genome have influenced fitness since the human-chimpanzee divergence,
      and they suggest that recent evolutionary turnover has had limited impact on the
      functional content of the genome. 

PMID- 25599401
TI  - Genetic architecture of artemisinin-resistant Plasmodium falciparum.
AB  - We report a large multicenter genome-wide association study of Plasmodium
      falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15
      locations in Southeast Asia, we identified at least 20 mutations in kelch13
      (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were
      associated with a slow parasite clearance rate after treatment with artemisinin
      derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast
      ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt
      (chloroquine resistance transporter) also showed strong associations with
      artemisinin resistance. Analysis of the fine structure of the parasite population
      showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic
      background on which kelch13 mutations are particularly likely to arise and that
      they correlate with the contemporary geographical boundaries and population
      frequencies of artemisinin resistance. These findings indicate that the risk of
      new resistance-causing mutations emerging is determined by specific predisposing
      genetic factors in the underlying parasite population. 

PMID- 25599407
TI  - Role of FXR in beta-cells of lean and obese mice.
AB  - We have recently shown that the bile acid (BA) taurochenodeoxycholate (TCDC)
      acutely stimulates insulin secretion via activation of the farnesoid X receptor
      (FXR). Aims of the current investigation were to discriminate between nongenomic
      (<=1 h) and genomic effects (24-48 h) of BAs on beta-cells and to evaluate
      whether FXR can modulate the adverse effects of a high-fat diet (HFD). TCDC (500
      nM) as well as glycine-conjugated and unconjugated CDC (chenodeoxycholate)
      increased insulin secretion in acute incubations but did not evoke additional
      effects after 1-2 days of preincubation. The BAs did not stimulate beta-cells of
      FXR-knockout (KO) mice and activation of the G protein-coupled BA receptor TGR5
      was ineffective, suggesting that FXR is the sole BA receptor in beta-cells
      activated by TCDC and its analogues. As opposed to lean mice, obese FXR-KO mice
      did not show HFD-induced glucose intolerance and increased fasting glucose. The
      beneficial impact of FXR-KO on glucose metabolism cannot be explained by an
      adaptive compensation of insulin secretion or beta-cell mass. Interestingly, in
      contrast to its effect on islets from lean mice, the FXR agonist GW4064 was
      ineffective in stimulating insulin secretion of islets from wild type mice fed a
      HFD or isolated islets kept in a glucolipotoxic medium. Additional feeding of CDC
      restored the effect of GW4064. CDC prevented HFD-induced impairment of glucose
      tolerance and in vitro effects of glucolipotoxicity. The data show that the FXR
      is the most important BA receptor in beta-cells and that FXR signaling in beta
      cells is impaired by overnutrition, which alters activatability of the FXR.

PMID- 25599408
TI  - Authors' response to the letter to the editor: "Effects of acoustic feedback
      training in elite-standard Para-Rowing" by Schaffert and Mattes (2015).
AB  - Our article in the Journal of Sports Sciences was designed to examine effects of
      auditory feedback on mean boat speed during on-water training of visually
      impaired athletes in elite-standard Para-Rowing. This aim is stated explicitly in
      the title, abstract, introduction and discussion section. The effects were
      analysed on the basis of a conservative approach to using inferential statistics
      by emphasising measures that communicate meaningful differences and effect sizes
      to help interpret the data's practical importance for sport competition.
      Biomechanical measurements have been combined with standardised questionnaires to
      assess the athletes' perceived experience during rowing with acoustic feedback.
      An application for high-performance rowing has already been used to successfully
      investigate the effects of acoustic feedback on the time structure of the rowing
      cycle during the recovery phase. In this response, we provide our comments to the
      concerns presented in the 'Letter to the Editor' along with a brief description
      of the issues that relate to research in high-performance sport. 

PMID- 25599410
TI  - IL-17A as a potential biomarker of IgA nephropathy.

PMID- 25599409
TI  - Far-red-absorbing cationic phthalocyanine photosensitizers: synthesis and
      evaluation of the photodynamic anticancer activity and the mode of cell death
      induction.
AB  - Novel zinc, magnesium, and metal-free octasubstituted phthalocyanine
      photosensitizers bearing [(triethylammonio)ethyl]sulfanyl substituents in the
      peripheral or nonperipheral positions were synthesized and investigated for their
      photophysical properties (PhiDelta value up to 0.91, lambdamax up to 750 nm) and
      photodynamic anticancer activity. The photodynamic treatment of 3T3, HeLa, SK-MEL
      28, and HCT 116 cancer cells revealed that the magnesium complexes were not
      active (IC50 > 100 MUM), whereas the IC50 values of the zinc complexes typically
      reached values in the submicromolar range with low toxicity in the dark (TC50 ~
      1500 MUM). The subcellular changes upon photodynamic treatment of the HeLa cells
      indicated that the studied photosensitizers induced damage primarily to the
      lysosomes, which was followed by a relocalization and damage to other organelles.
      The time-lapse morphological changes along with the flow cytometry and caspase
      activity measurements indicated a predominant involvement of necrosis-like cell
      death. 

PMID- 25599411
TI  - Psychosocial and demographic correlates of the discontinuation of in vitro
      fertilization.
AB  - In this study, we investigated the relationship between psychosocial factors
      assessed pre-treatment and the discontinuation of in vitro fertilisation (IVF)
      treatment after one year. A cohort study was performed in a Dutch fertility
      clinic and included 667 couples. Demographic characteristics, scores for
      psychosocial factors, discontinuation rates, reasons for discontinuation and
      outcome data of the treatment were measured. Discontinuation due to personal
      reasons was differentiated from discontinuation because of changing a clinic or
      physicians' advice. The results showed that 37.5% of the couples became pregnant,
      while 40 (6%) discontinued IVF treatment because of personal reasons. A sample
      size of 288 women remained for analysis. A longer duration of infertility, less
      perceived social support in women and higher scores on acceptance of infertility
      in both men and women were significantly correlated with discontinuation.
      Multivariate analysis, using these variables including the age of the women,
      showed that these factors could explain 29% of the discontinuation. These results
      point to a differentiation between couples who choose positively choose to
      discontinue treatment and those discontinuing from a more negative perspective.
      Opportunities to tailor interventions to this second group of couples need to be
      investigated. 

PMID- 25599412
TI  - Metabolomics of four biofluids from dairy cows: potential biomarkers for milk
      production and quality.
AB  - The fundamental understanding of the mechanisms regulating milk protein synthesis
      is limited. This study aimed to elucidate the metabolic mechanisms of milk
      production affected by forage quality through studying metabolites from four
      biofluids (rumen fluid, milk, serum, and urine) collected from 16 lactating cows
      fed alfalfa hay (AH, high-quality, n = 8) and corn stover (CS, low-quality, n =
      8) using gas chromatography-time-of-flight/mass spectrometry. The cows fed AH
      exhibited higher milk yield (P < 0.01), milk protein yield (P = 0.04), and milk
      efficiency (P < 0.01) than those fed CS. A total of 165, 195, 218, and 156
      metabolites were identified in the rumen fluid, milk, serum, and urine,
      respectively, while 29 metabolites were found in all four biofluids. In addition
      55, 8, 28, and 31 metabolites in each biofluid were significantly different (VIP
      > 1 and P < 0.05) between the AH- and CS-fed animals. These metabolites were
      involved in glycine, serine, and threonine metabolism; tyrosine metabolism; and
      phenylalanine metabolism. Further integrated key metabolic pathway analysis
      showed that the AH-fed cows may have more comprehensive amino acid metabolisms,
      suggesting that these metabolite-associated pathways may serve as biomarkers for
      higher milk yield and better milk protein quality. 

PMID- 25599413
TI  - Antibiotic Susceptibility Patterns of Mycobacterium tuberculosis Isolates from
      Guizhou Province of China Against 13 Antituberculosis Drugs.
AB  - A total of 92 Mycobacterium tuberculosis isolates were collected from patients
      with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012.
      Collected isolates were used to determine antibiotic susceptibility patterns
      against 13 anti-TB drugs: 4 first-line and 9 second-line (ciprofloxacin,
      gatifloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, amikacin,
      capreomycin, kanamycin, and prothionamide) drugs. Results showed that among 57
      new cases of TB only 66.7% were susceptible to all four first-line anti-TB drugs
      and 64.9% were susceptible to fluoroquinolones and second-line injectables; 10.5%
      of new and 22.9% of previously treated cases were multidrug-resistant TB (MDR
      TB); and 1.8% of new and 2.9% of previously treated cases were extensively drug
      resistant TB (XDR-TB). In addition, 14.3% of MDR-TB cases (2 out of 14) were XDR
      TB, which is higher than the average numbers in China (about 8%) and in the world
      (9.6%). This study confirms that primary transmission of drug-resistant TB,
      including MDR/XDR-TB, is a real threat to achieving effective control of drug
      resistant TB in the Guizhou Province and indicates the necessity to determine
      antibiotic susceptibility patterns in patients with TB to improve treatment
      outcomes. 

PMID- 25599414
TI  - Predictors of early mortality in a cohort of HIV-infected children receiving high
      active antiretroviral treatment in public hospitals in Ethiopia.
AB  - Highly active antiretroviral therapy (HAART) is the breakthrough in care and
      treatment of people living with HIV, leading to a reduction in mortality and an
      improvement in the quality of life. Without antiretroviral treatment, most HIV
      infected children die before their fifth birthday. So the objective of this study
      is to determine the mortality and associated factors in a cohort of HIV-infected
      children receiving ART in Ethiopia. A multicentre facility-based retrospective
      cohort study was done in selected pediatric ART units in hospitals found in Addis
      Ababa, Ethiopia. The probability of survival was estimated using the Kaplan-Meier
      method, and multivariate analysis by Cox proportional hazards regression models
      was conducted to determine the independent predictor of survival. A total of 556
      children were included in this study. Of the total children, 10.4% were died in
      the overall cohort. More deaths (70%) occurred in the first 6 months of ART
      initiation, and the remaining others were still on follow-up at different
      hospitals. Underweight (moderate and severe; HR: 10.10; 95% CI: 2.08, 28.00; P =
      0.004; and HR: 46.69; 95% CI: 9.26, 200.45; P < 0.01, respectively), advanced
      disease stage (WHO clinical stages III and IV; HR: 10.13: 95% CI: 2.25, 45.58; P
      = 0.003), poor ART adherence (HR: 11.72; 95% CI: 1.60, 48.44; P = 0.015), and
      hemoglobin level less than 7 g/dl (HR: 4.08: 95% CI: 1.33, 12.56; P = 0.014) were
      confirmed as significant independent predictors of death after controlling for
      other factors. Underweight, advanced disease stage, poor adherence to ART, and
      anemia appear to be independent predictor of survival in HIV-infected children
      receiving HAART at the pediatric units of public hospitals in Ethiopia.
      Nutritional supplementations, early initiation of HAART, close supervision, and
      monitoring of patients during the first 6 months, the follow up period is
      recommended. 

PMID- 25599415
TI  - Prostate Imaging Reporting and Data System and Likert Scoring System:
      Multiparametric MR Imaging Validation Study to Screen Patients for Initial
      Biopsy.
AB  - PURPOSE: To compare the diagnostic performance of the magnetic resonance (MR)
      imaging-based Prostate Imaging Reporting and Data System (PI-RADS) and a Likert
      scale in the detection of prostate cancer in a cohort of patients undergoing
      initial prostate biopsy. MATERIALS AND METHODS: This institutional review board
      approved two-center prospective study included 118 patients with normal digital
      rectal examination (DRE) results but elevated prostate-specific antigen (PSA)
      levels (4-20 ng/mL) who were referred for initial prostate biopsies and had one
      suspicious (Likert scale score, >=3) focus at prebiopsy 1.5-T multiparametric MR
      imaging performed with T2-weighted, diffusion-weighted [DW], and dynamic contrast
      material-enhanced imaging. Targeted core biopsies and random systematic core
      biopsies were performed. The elementary unit for analysis was the core.
      Relationships were assessed by using the Mann-Whitney U test. Yates corrected and
      Pearson chi(2) tests were used to evaluate categoric variables. A training set
      was randomly drawn to construct the receiver operating characteristic curves for
      the summed PI-RADS scores and for the Likert scale scores. The thresholds to
      recommend biopsy were obtained from the Youden J statistics and were tested in
      the remaining validation set in terms of predictive characteristics.
      Interobserver variability was analyzed by using weighed kappa statistics in a
      random set of 50 patients. RESULTS: Higher T2-weighted, DW, and dynamic contrast
      enhanced imaging PI-RADS scores were observed in areas that yielded cancer
      positive cores. The percentage of positive cores increased with the sum of scores
      aggregated in five classes as follows: For summed PI-RADS scores of 3-5, the
      percentage of positive cores was 2.3%; for scores of 6-8, it was 5.8%; for scores
      of 9 or 10, it was 24.7%; for scores of 11 or 12, it was 51.8%; and for scores of
      13-15, it was 72.1% (P for trend, <.0001). For the threshold of summed PI-RADS
      scores of 9 or greater, sensitivity was 86.6%, specificity was 82.4%, the
      positive predictive value was 52.4%, the negative predictive value was 96.5%, and
      accuracy was 83.2%. The respective data for Likert scale scores of 3 or greater
      were 93.8%, 73.6%, 44.3%, 98.1%, and 73.3%. Good interobserver agreement was
      observed for the Likert scale (kappa = 0.80) and the summed PI-RADS (kappa =
      0.73) scoring systems. CONCLUSION: PI-RADS provided the site-specific stratified
      risk of cancer-positive cores in biopsy-naive men with normal DRE results and
      elevated PSA levels. There was no significant difference between summed PI-RADS
      scores of 9 or greater and Likert scale scores of 3 or greater in the detection
      of cancer in the peripheral zone.

PMID- 25599416
TI  - The focus of this series will be on highlighting topics that are relevant to
      clinical neuropsychology, yet have remained, for one reason or another, outside
      the scope of routine clinical practice.

PMID- 25599417
TI  - Milestones and millstones-moving healthcare forward.

PMID- 25599418
TI  - Photon upconversion in supramolecular gel matrixes: spontaneous accumulation of
      light-harvesting donor-acceptor arrays in nanofibers and acquired air stability.
AB  - Efficient triplet-triplet annihilation (TTA)-based photon upconversion (UC) is
      achieved in supramolecular organogel matrixes. Intense UC emission was observed
      from donor (sensitizer)-acceptor (emitter) pairs in organogels even under air
      saturated condition, which solved a major problem: deactivation of excited
      triplet states and TTA-UC by molecular oxygen. These unique TTA-UC molecular
      systems were formed by spontaneous accumulation of donor and acceptor molecules
      in the gel nanofibers which are stabilized by developed hydrogen bond networks.
      These molecules preorganized in nanofibers showed efficient transfer and
      migration of triplet energy, as revealed by a series of spectroscopic,
      microscopic, and rheological characterizations. Surprisingly, the donor and
      acceptor molecules incorporated in nanofibers are significantly protected from
      the quenching action of dissolved molecular oxygen, indicating very low
      solubility of oxygen to nanofibers. In addition, efficient TTA-UC is achieved
      even under excitation power lower than the solar irradiance. These observations
      clearly unveil the adaptive feature of host gel nanofiber networks that allows
      efficient and cooperative inclusion of donor-acceptor molecules while maintaining
      their structural integrity. As evidence, thermally induced reversible
      assembly/disassembly of supramolecular gel networks lead to reversible modulation
      of the UC emission intensity. Moreover, the air-stable TTA-UC in supramolecular
      gel nanofibers was generally observed for a wide combination of donor-acceptor
      pairs which enabled near IR-to-yellow, red-to-cyan, green-to-blue, and blue-to-UV
      wavelength conversions. These findings provide a new perspective of air-stable
      TTA-UC molecular systems; spontaneous and adaptive accumulation of donor and
      acceptor molecules in oxygen-blocking, self-assembled nanomatrixes. The oxygen
      barrier property of l-glutamate-derived organogel nanofibers has been unveiled
      for the first time, which could find many applications in stabilizing air
      sensitive species in aerated systems. 

PMID- 25599419
TI  - Physiological behaviour of gliotoxigenic Aspergillus fumigatus sensu stricto
      isolated from maize silage under simulated environmental conditions.
AB  - Environmental conditions play a key role in fungal development. During the silage
      production process, humidity, oxygen availability and pH vary among lactic
      fermentation phases and among different silage sections. The aim of this work was
      to study the physiological behaviour of gliotoxicogenic Aspergillus fumigatus
      strains isolated from maize silage under simulated natural physicochemical
      conditions - different water activities (a(W)), temperatures (To), pH and oxygen
      pressure - on the growth parameters (growth rate and lag phase) and gliotoxin
      production. The silage was made with the harvested whole maize plant that was
      chopped and used for trench-type silo fabrication. Water activity and pH of the
      silage samples were determined. Total fungal counts were performed on Dichloran
      Rose Bengal Chloramphenicol agar and Dichloran 18% Glycerol agar. The
      morphological identification of A. fumigatus was performed with different culture
      media and at different growth temperature to observe microscopic and macroscopic
      characteristics. Gliotoxin production by A. fumigatus was determined by HPLC. All
      strains isolated were morphologically identified as A. fumigatus. Two A.
      fumigatus strains isolated from the silage samples were selected for the
      ecophysiological study (A. fumigatus sensu stricto RC031 and RC032). The results
      of this investigation showed that the fungus grows in the simulated natural
      physicochemical conditions of corn silage and produces gliotoxin. The study of
      the physiological behaviour of gliotoxigenic A. fumigatus under simulated
      environmental conditions allowed its behaviour to be predicted in silage and this
      will in future enable appropriate control strategies to be developed to prevent
      the spread of this fungus and toxin production that leads to impairment and
      reduced quality of silage.

PMID- 25599420
TI  - Antibacterial Investigation of Thyme Essential Oil and Its Main Constituents in
      Combination with Tetracycline.
AB  - The chemical composition and antibacterial activity of Thymus glabrescens Willd.
      (thyme) essential oil were examined, as well as its association with
      tetracycline. The antibacterial activities of geraniol and thymol, the main
      constituents of T. glabrescens oil, were also determined. Gas chromatography and
      gas chromatography/mass spectrometry were used to analyze the chemical
      composition of the oil. The antibacterial activities of the oil, geraniol, and
      thymol were investigated by the broth microdilution method. The interactions of
      the essential oil, geraniol, and thymol with tetracycline, toward five selected
      strains, were evaluated using the microdilution checkerboard assay. Oxygenated
      monoterpenes were the most abundant compound class in the oil (57.14%), with
      geraniol (22.33%) as the major compound. The essential oil exhibited in vitro
      antibacterial activity against all tested bacterial strains. The combinations,
      essential oil-tetracycline and thymol-tetracycline, produced synergistic
      interaction to a greater extent compared with geraniol-tetracycline association.
      All synergistic combinations reduced the minimum effective dose of the antibiotic
      and, consequently, minimized its adverse side effects. 

PMID- 25599422
TI  - Resistance, rupture and repetition: Civil society strategies against intimate
      partner violence in Cambodia.
AB  - This paper offers a new interpretation of the 'resistance' carried out by local
      civil society organisations in Cambodia against intimate partner violence (IPV).
      In this, the paper explores the nexus between 'rupture', 'resistance' and
      'repetition' and concludes that different 'repetitions' can contribute to acts of
      violence while simultaneously creating possibilities for resisting IPV. In regard
      to the latter, the concept of 'rupture' is investigated as a performative
      politics through which organisations try to disrupt the 'repetitions' of violent
      masculinities. Furthermore, it is argued that the importance of 'repetitions' and
      the concept of time should be acknowledged. The French criminal defence lawyer
      Jacques Verges' understanding of 'rupture' and the French philosopher Gilles
      Deleuze's notions of 'repetition' inform the analysis. To exemplify our
      discussion and findings, the paper embraces stories of a number of civil society
      workers who facilitate various men's groups in Cambodia in order to negotiate the
      practice of IPV. 

PMID- 25599421
TI  - A possible route for foodborne transmission of Clostridium difficile?
AB  - Spores of toxigenic Clostridium difficile and spores of food-poisoning strains of
      Clostridium perfringens show a similar prevalence in meats. Spores of both
      species are heat resistant and can survive cooking of foods. C. perfringens is a
      major cause of foodborne illness; studies are needed to determine whether C.
      difficile transmission by a similar route is a cause of infection. 

PMID- 25599423
TI  - An image stabilization optical system using deformable freeform mirrors.
AB  - An image stabilization optical system using deformable freeform mirrors is
      proposed that enables the ray sets to couple dynamically in the object and image
      space. It aims to correct image blurring and degradation when there is relative
      movement between the imaging optical axis and the object. In this method,
      Fermat's principle and matrix methods are used to describe the optical path of
      the entire optical system with a shift object plane and a fixed corresponding
      image plane in the carrier coordinate system. A constant optical path length is
      determined for each ray set, so the correspondence between the object and the
      shift free image point is used to calculate the solution to the points on the
      surface profile of the deformable mirrors (DMs). Off-axis three-mirror
      anastigmats are used to demonstrate the benefits of optical image stabilization
      with one- and two-deformable mirrors. 

PMID- 25599424
TI  - Embroidered electrode with silver/titanium coating for long-term ECG monitoring.
AB  - For the long-time monitoring of electrocardiograms, electrodes must be skin
      friendly and non-irritating, but in addition they must deliver leads without
      artifacts even if the skin is dry and the body is moving. Today's adhesive
      conducting gel electrodes are not suitable for such applications. We have
      developed an embroidered textile electrode from polyethylene terephthalate yarn
      which is plasma-coated with silver for electrical conductivity and with an ultra
      thin titanium layer on top for passivation. Two of these electrodes are embedded
      into a breast belt. They are moisturized with a very low amount of water vapor
      from an integrated reservoir. The combination of silver, titanium and water vapor
      results in an excellent electrode chemistry. With this belt the long-time
      monitoring of electrocardiography (ECG) is possible at rest as well as when the
      patient is moving. 

PMID- 25599425
TI  - Research trends in wireless visual sensor networks when exploiting
      prioritization.
AB  - The development of wireless sensor networks for control and monitoring functions
      has created a vibrant investigation scenario, where many critical topics, such as
      communication efficiency and energy consumption, have been investigated in the
      past few years. However, when sensors are endowed with low-power cameras for
      visual monitoring, a new scope of challenges is raised, demanding new research
      efforts. In this context, the resource-constrained nature of sensor nodes has
      demanded the use of prioritization approaches as a practical mechanism to lower
      the transmission burden of visual data over wireless sensor networks. Many works
      in recent years have considered local-level prioritization parameters to enhance
      the overall performance of those networks, but global-level policies can
      potentially achieve better results in terms of visual monitoring efficiency. In
      this paper, we make a broad review of some recent works on priority-based
      optimizations in wireless visual sensor networks. Moreover, we envisage some
      research trends when exploiting prioritization, potentially fostering the
      development of promising optimizations for wireless sensor networks composed of
      visual sensors. 

PMID- 25599426
TI  - Pose estimation with a Kinect for ergonomic studies: evaluation of the accuracy
      using a virtual mannequin.
AB  - Analyzing human poses with a Kinect is a promising method to evaluate potentials
      risks of musculoskeletal disorders at workstations. In ecological situations,
      complex 3D poses and constraints imposed by the environment make it difficult to
      obtain reliable kinematic information. Thus, being able to predict the potential
      accuracy of the measurement for such complex 3D poses and sensor placements is
      challenging in classical experimental setups. To tackle this problem, we propose
      a new evaluation method based on a virtual mannequin. In this study, we apply
      this method to the evaluation of joint positions (shoulder, elbow, and wrist),
      joint angles (shoulder and elbow), and the corresponding RULA (a popular
      ergonomics assessment grid) upper-limb score for a large set of poses and sensor
      placements. Thanks to this evaluation method, more than 500,000 configurations
      have been automatically tested, which would be almost impossible to evaluate with
      classical protocols. The results show that the kinematic information obtained by
      the Kinect software is generally accurate enough to fill in ergonomic assessment
      grids. However inaccuracy strongly increases for some specific poses and sensor
      positions. Using this evaluation method enabled us to report configurations that
      could lead to these high inaccuracies. As a supplementary material, we provide a
      software tool to help designers to evaluate the expected accuracy of this sensor
      for a set of upper-limb configurations. Results obtained with the virtual
      mannequin are in accordance with those obtained from a real subject for a limited
      set of poses and sensor placements. 

PMID- 25599427
TI  - A fast and precise indoor localization algorithm based on an online sequential
      extreme learning machine.
AB  - Nowadays, developing indoor positioning systems (IPSs) has become an attractive
      research topic due to the increasing demands on location-based service (LBS) in
      indoor environments. WiFi technology has been studied and explored to provide
      indoor positioning service for years in view of the wide deployment and
      availability of existing WiFi infrastructures in indoor environments. A large
      body of WiFi-based IPSs adopt fingerprinting approaches for localization.
      However, these IPSs suffer from two major problems: the intensive costs of
      manpower and time for offline site survey and the inflexibility to environmental
      dynamics. In this paper, we propose an indoor localization algorithm based on an
      online sequential extreme learning machine (OS-ELM) to address the above problems
      accordingly. The fast learning speed of OS-ELM can reduce the time and manpower
      costs for the offline site survey. Meanwhile, its online sequential learning
      ability enables the proposed localization algorithm to adapt in a timely manner
      to environmental dynamics. Experiments under specific environmental changes, such
      as variations of occupancy distribution and events of opening or closing of
      doors, are conducted to evaluate the performance of OS-ELM. The simulation and
      experimental results show that the proposed localization algorithm can provide
      higher localization accuracy than traditional approaches, due to its fast
      adaptation to various environmental dynamics. 

PMID- 25599428
TI  - Feldenkrais method-based exercise improves quality of life in individuals with
      Parkinson's disease: a controlled, randomized clinical trial.
AB  - CONTEXT: Longevity results in changes to patterns of health, with an increased
      prevalence of chronic diseases. Parkinson's disease (PD) is described as a
      progressive neurodegenerative disease related to age that influences quality of
      life (QoL) and leads to depression. OBJECTIVE: The study intended to assess
      changes in QoL and depression in older adults with PD through use of Feldenkrais
      method-based exercise. DESIGN: The study was a controlled, blinded, and
      randomized clinical trial. SETTING: The study occurred at the University Hospital
      of the Federal University of Sergipe in Aracaju, Sergipe, Brazil. PARTICIPANTS:
      Participants were 30 patients, aged between 50 and 70 y, with idiopathic PD, who
      signed an informed consent form and were randomly assigned to 2 groups: treatment
      and control. INTERVENTION: The treatment group underwent 50 sessions of an
      exercise program based on the Feldenkrais method. The control group received
      educational lectures during this period. The treatment group's 50 sessions, given
      2 */wk on alternate days and lasting 60 min, were conducted in an appropriate
      room at the hospital. OUTCOME MEASURES: Two surveys, the Parkinson's Disease
      Quality of Life (PDQL) questionnaire and the Beck Depression Inventory (BDI),
      were administered before and after the sessions for both groups. RESULTS: After
      the exercises based on the Feldenkrais method, the treated group showed
      improvement in QoL scores (P = .004) as well as a reduction in the level of
      depression (P = .05) compared with the control group. CONCLUSION: The findings in
      the current study indicate that it is likely that the practice of a program based
      on the Feldenkrais method can contribute greatly to the QoL of patients with PD,
      suggesting the importance of interventions that promote wellness for this
      population.

PMID- 25599429
TI  - The relevance of using the C3d/immunoglobulin G test in clinical intervention.
AB  - CONTEXT: A large subset of the population is afflicted with a wide range of food
      related inflammatory conditions, with at least 100 million people affected
      worldwide. The C3d/immunoglobulin G (IgG) test measures both the innate and
      adaptive responses of the immune system. OBJECTIVE: The study intended to
      validate the C3d/IgG test for food sensitivity for its ability to manage the
      symptoms of patients with intestinal and extraintestinal symptoms. DESIGN: The
      research team designed a retrospective study based on a cohort of patients
      treated at a medical center. SETTING: The patients were seen at Progressive
      Medical Center of Atlanta, an integrative medicine clinic, and patients' samples
      were analyzed at Dunwoody Laboratory. PARTICIPANTS: The study included 30
      individuals, 9 males and 21 females, ranging in age from 7-71 y who presented
      with symptoms associated with food sensitivity. INTERVENTION: The study reviewed
      the treatment and results of patients who were placed on an exclusion dietary
      regimen for treatment of possible food sensitivity. From an initial C3d/IgG test,
      foods causing elevated anti-C3d/IgG, with the exception of ones causing mild
      reactions, were identified and eliminated from each patient's diet. OUTCOME
      MEASURES: At baseline and at an average of 10.7 mo on the dietary regimen, 2
      C3d/IgG tests were performed on each patient's serum by the method of indirect
      enzyme-linked immunosorbent assay (ELISA). Both food sensitivities and chief
      complaints were reassessed in that second test to determine if participants'
      symptoms improved with food elimination. Outcomes were based on the status of the
      patients' primary complaints. RESULTS: Patients who complied with the avoidance
      of anti-C3d/IgG dietary antigens demonstrated a statistically significant
      reduction in C3d/IgG-testing sensitivity and a marked reduction in symptoms that
      they had reported before beginning the diet. The P values were .000002, .007, and
      .001 for changes in the severe, high, and moderate test results, respectively,
      between the initial and second test. CONCLUSION: Overall, patients' well-being
      improved when C3d/IgG food sensitivity decreased as a result of an exclusion
      diet, demonstrating that food removal based on the C3d/IgG test could be an
      effective approach to patients' care.

PMID- 25599430
TI  - Literature review: pharmacists' interventions to improve control and management
      in type 2 diabetes mellitus.
AB  - Diabetes mellitus (DM) is a common disease in which excessive levels of blood
      glucose (sugar) occur. In simple terms, diabetes is generally due to failure in
      the effective functioning of insulin. Common types of diabetes include type 1 and
      type 2, which have different treatment options. In the general population, type 2
      diabetes is more prevalent than type 1, and type 2 accounts for more than 90% of
      all known cases of diabetes. The current review examines the contributions of
      pharmacists to the more positive, long-term prognosis of patients with DM through
      improvements in its control and management. The authors conducted a systematic
      literature search. Twenty-seven studies were identified that demonstrated the
      effects of a pharmacist's intervention on glycated hemoglobin (HbA1c). In all
      cases, it was reported that the intervention was successful in reducing HbA1c in
      patients with DM. Pharmacist interventions have also proven successful in
      improving patient lipid profiles, cardiovascular outcomes, and body mass indexes
      (BMIs), and in reducing other complications associated with the disease. It was
      also reported that economic advantages were associated with a pharmacist's
      management of DM. 

PMID- 25599431
TI  - The therapeutic effect and possible harm of puerarin for treatment of stage III
      diabetic nephropathy: a meta-analysis.
AB  - CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage kidney disease
      in developed countries. Current therapy can slow the rate of progression of DN,
      but eventually end-stage renal failure will occur in a proportion of patients.
      Identification of new strategies and additional complementary and alternative
      therapies for treating DN are important. OBJECTIVE: The research team wanted to
      assess the beneficial and harmful effects of using puerarin plus angiotensin
      converting enzyme inhibitor (ACEI) compared with using only ACEI for treatment of
      individuals with stage III DN. DESIGN: The research team performed a meta
      analysis of randomized, controlled trials (RCTs) by searching the following
      electronic databases: (1) the Cochrane Database of Systematic Reviews, (2) the
      Cochrane Central Register of Controlled Trials (CENTRAL), (3) PubMed, (4) EMBASE
      (Elsevier), (5) the Allied and Complementary Medicine Database (AMED), (6) the
      Chinese Biomedicine Database (CBM), (7) the China National Knowledge
      Infrastructure (CNKI), and (8) the Chinese Biomedical Journals (VIP), with no
      language restrictions, as well as databases of clinical trials. OUTCOME MEASURES:
      Measured outcomes included (1) urinary protein measured as urinary albumin
      excretion rate (UAER) (MUg/min) and 24-h urine protein (24-h UP) (mg/24 h); (2)
      renal function measured as blood urea nitrogen (BUN) (mmol/L) and serum
      creatinine (SCr) (MUmol/L); (3) alpha1-microglobulin (alpha1-MG) (mg/24 h) and
      endothelin-1 (ET-1) (ng/24 h); (4) end points (EPs); and (5) adverse events
      (AEs). RESULTS: Ten RCTs involving 669 participants were included. All trials
      were conducted and published in China. Treatment of DN with puerarin plus ACEI
      significantly decreased the UAER-P < .0001, MD = -23.43 (95% CI, -33.95 to 
      12.91), and had no effect on 24-h UP-P = .09, MD = -56.76 (95% CI, -122.65 to
      9.12); BUN-P = .17, MD = -0.51 (95% CI, -1.24 to 0.21); and SCr-P = .26, MD = 
      4.43 (95% CI, -12.05 to 3.20). One trial reported abdominal discomfort and nausea
      (2 cases) in the treatment group. CONCLUSIONS: Puerarin may be a beneficial
      therapy for treating DN; however, this hypothesis needs to be proven by
      additional high-quality studies using large samples and multicenter evidence.

PMID- 25599432
TI  - Paul G. Harch, MD: the genetically modulated healing effects of hyperbaric oxygen
      therapy.

PMID- 25599433
TI  - The effect of methadone dose regimen on neonatal abstinence syndrome.
AB  - OBJECTIVES: To evaluate the effects of a multiple daily dose methadone regimen in
      pregnancy on neonatal outcomes. METHODS: Although methadone maintenance has been
      the standard for the treatment of opioid dependence in pregnancy, there is no
      consensus on proper dosing. Single daily dosing is the most common strategy.
      Because of accelerated metabolism of methadone in pregnancy, this regimen may
      expose mother and fetus to daily episodes of withdrawal and possibly contribute
      to more severe Neonatal Abstinence Syndrome (NAS). This study reports on a
      protocol that increased both methadone dose and dose frequency in response to
      maternal reports of withdrawal. RESULTS: Treatment of NAS was needed in 29% of
      neonates, compared to a published rate of 60% to 80%. The mean methadone dose was
      152 mg at delivery, divided into 2 to 6 doses per day. Ninety-two percent of
      mothers were free of illicit drug use at delivery. There was no relationship
      between methadone dose and treatment of NAS. Female babies had a treatment rate
      of 16% versus 38% for male babies. Beyond abstinence symptoms, cohort outcomes in
      terms of gestational age, birth weight, prematurity, Caesarian sections, and
      breastfeeding equaled or approximated US population norms. CONCLUSIONS: The
      protocol was associated with low rates of treatment of NAS and high rates of
      maternal recovery. High rates of treatment for NAS reported in methadone-exposed
      neonates might relate in part to iatrogenic factors and be reduced through the
      use of divided daily doses and protocols that minimize maternal withdrawal.

PMID- 25599436
TI  - Employment of synthetic patch with augmentation of the long head of the biceps
      tendon in irreparable lesions of the rotator cuff: our technique applied to 60
      patients.
AB  - BACKGROUND: The aim of our study was to evaluate the effectiveness of both
      clinical and functional benefits after the surgical repair of the rotator cuff in
      irreparable lesions using a synthetic patch with augmentation of the long head of
      the biceps (LHB) tendon. METHODS: This is a retrospective study analysis of a
      randomized series of 60 patients (45 women and 15 men; average age 66 y) who
      underwent open repair of irreparable rotator cuff tear with synthetic patch using
      LHB tendon augmentation between 1999 and 2008.The inclusion criteria were:
      patients painful symptomatology, presenting a deficit in elevation, who are not
      responsive to physiotherapy, irreparable tear size, minimum follow-up of 36
      months after surgery, and active and motivated patients. We used a control group
      of 60 patients treated without employment of the synthetic patch and LHB tendon
      augmentation.Patients were evaluated preoperatively and after 36 months with a
      Visual Analog Scale (VAS) and the University of California, Los Angeles (UCLA)
      shoulder rating scale and by measuring elevation of the scapular plane and
      strength with a dynamometer. All the patients were assessed preoperatively also
      with plain radiographs (anteroposterior and axillary views), ultrasound, and NMRI
      of the shoulder. The VAS and UCLA scores were also obtained 3 months
      postoperatively. Tendon integrity was assessed after 1 year by NMRI. Statistical
      analysis was conducted by 1-way analysis of variance between groups of treatment,
      with Dunnett post hoc correction for multiple comparisons. P-values <= 0.05 were
      considered as statistically significant. This surgical technique consisted in a
      short deltoid splitting, irreparable lesion evaluation, and, after tenodesis, the
      proximal segment of the LHB tendon was sutured to the remaining cuff tendons to
      fill the gap of the corresponding lesion. To shield the repaired rotator cuff we
      inserted a synthetic patch. RESULTS: Satisfactory results were achieved in 52 of
      the patients treated with this procedure; after 3 months the mean VAS was 6.85 +/
      1.11 versus 4.9 +/- 0.9, whereas the mean UCLA was 11.28 +/- 1.43 versus 20.85
      +/- 1.27, respectively, for control and prolene group. After 36 months the mean
      VAS was 3.7 +/- 1.01 versus 3.23 +/- 1.07, whereas the mean UCLA was 14.73 +/-
      1.96 versus 24.6 +/- 3.3, respectively, for control and prolene group. In
      addition, after 36 months elevation on the scapular plane was 140.75 +/- 10.48
      degrees versus 174.75 +/- 8.1 degrees and abduction strength was 8.57 kg +/- 0.63
      versus 13.61 kg +/- 0.84, respectively, for control and prolene group (P-value =
      0.005). Re-tear rate after 12 months was 40% (24/60) in the control group and 15%
      (9/60) in the prolene group. No adverse side effects (infection, rejection,
      allergy) were reported during the study period. CONCLUSIONS: The results of our
      study suggest that employing this surgical technique in patients (appropriately
      selected) with an irreparable rotator cuff tear can lead to pain relief and
      improved clinical outcome.

PMID- 25599434
TI  - Methamphetamines and pregnancy outcomes.
AB  - INTRODUCTION: Methamphetamine (MA) is one of the most commonly used illicit drugs
      in pregnancy, yet studies on MA-exposed pregnancy outcomes have been limited
      because of retrospective measures of drug use; lack of control for confounding
      factors; other drug use, including tobacco; poverty; poor diet; and lack of
      prenatal care. This study presents prospective collected data on MA use and birth
      outcomes, controlling for most confounders. MATERIALS AND METHODS: This is a
      retrospective cohort study of women obtaining prenatal care from a clinic
      treating women with substance use disorders, on whom there are prospectively
      obtained data on MA and other drug use, including tobacco. Methamphetamine
      exposed pregnancies were compared with non-MA exposed pregnancies and non-drug
      exposed pregnancies, using univariate and multivariate analysis to control for
      confounders. RESULTS: One hundred forty-four infants were exposed to MA during
      pregnancy, 50 had first trimester exposure only, 45 had continuous use until the
      second trimester, 29 had continuous use until the third trimester, but were
      negative at delivery, and 20 had positive toxicology at delivery. There were 107
      non-MA-exposed infants and 59 infants with no drug exposure. Mean birth weights
      were the same for MA-exposed and nonexposed infants (3159 g vs 3168 g; P = 0.9),
      although smaller than those without any drug exposure (3159 vs 3321; P = 0.04),
      infants with positive toxicology at birth (meconium or urine) were smaller than
      infants with first trimester exposure only (2932 g vs 3300 g; P = 0.01).
      Gestation was significantly shorter among the MA-exposed infants than that among
      nonexposed infants (38.5 vs 39.1 weeks; P = 0.045), and those with no drug
      exposure (38.5 vs 39.5; P = 0.0011), the infants with positive toxicology at
      birth had a clinically relevant shortening of gestation (37.3 weeks vs 39.1; P =
      0.0002). CONCLUSIONS: Methamphetamine use during pregnancy is associated with
      shorter gestational ages and lower birth weight, especially if used continuously
      during pregnancy. Stopping MA use at any time during pregnancy improves birth
      outcomes, thus resources should be directed toward providing treatment and
      prenatal care.

PMID- 25599437
TI  - Reply to: Adjusting tracheal tube cuff pressure.

PMID- 25599438
TI  - Intricacies of good communication in the context of pain: does validation
      reinforce disclosure?

PMID- 25599439
TI  - What can the POINT study tell us?

PMID- 25599440
TI  - Early changes in somatosensory function in spinal pain: a systematic review and
      meta-analysis.
AB  - Alterations in sensory processing have been demonstrated in chronic low back and
      neck pain. However, it has not been yet systematically summarized how early these
      changes occur in spinal pain. This systematic review examines the available
      literature measuring somatosensory function in acute (<6 weeks) and subacute (6
      12 weeks) spinal pain. The protocol for this review has been registered on the
      International Prospective Register of Systematic Reviews (PROSPERO). An
      electronic search of 4 databases was conducted to retrieve studies assessing
      somatosensory function by quantitative sensory testing in adults with spinal pain
      of up to 12 weeks duration. Two reviewers independently screened the studies and
      assessed the risk of bias. Studies were grouped according to spinal pain
      condition (whiplash injury, idiopathic neck pain, and nonspecific low back pain),
      and, where possible, meta-analyses were performed for comparable results. Fifteen
      studies were included. Sources of bias included lack of assessor blinding,
      unclear sampling methods, and lack of control for confounders. We found that: (1)
      there is consistent evidence for thermal and widespread mechanical pain
      hypersensitivity in the acute stage of whiplash, (2) there is no evidence for
      pain hypersensitivity in the acute and subacute stage of idiopathic neck pain,
      although the body of evidence is small, and (3) hyperalgesia and spinal cord
      hyperexcitability have been detected in early stages of nonspecific low back
      pain, although evidence about widespread effects are conflicting. Future
      longitudinal research using multiple sensory modalities and standardized testing
      may reveal the involvement of somatosensory changes in the development and
      maintenance of chronic pain. 

PMID- 25599441
TI  - Validating pain communication: current state of the science.

PMID- 25599442
TI  - Peripheral and spinal circuits involved in mechanical allodynia.

PMID- 25599443
TI  - Cortical activity evoked by inoculation needle prick in infants up to one-year
      old.
AB  - Inoculation is one of the first and most common experiences of procedural pain in
      infancy. However, little is known about how needle puncture pain is processed by
      the central nervous system in children. In this study, we describe for the first
      time the event-related activity in the infant brain during routine inoculation
      using electroencephalography. Fifteen healthy term-born infants aged 1 to 2
      months (n = 12) or 12 months (n = 5) were studied in an outpatient clinic. Pain
      behavior was scored using the Modified Behavioral Pain Scale. A distinct
      inoculation event-related vertex potential, consisting of 2 late negative
      positive complexes, was observable in single trials after needle contact with the
      skin. The amplitude of both negative-positive components was significantly
      greater in the 12-month group. Both inoculation event-related potential amplitude
      and behavioral pain scores increased with age but the 2 measures were not
      correlated with each other. These components are the first recordings of brain
      activity in response to real-life needle pain in infants up to a year old. They
      provide new evidence of postnatal nociceptive processing and, combined with more
      traditional behavioral pain scores, offer a potentially more sensitive measure
      for testing the efficacy of analgesic protocols in this age group. 

PMID- 25599444
TI  - The Pain and Opioids IN Treatment study: characteristics of a cohort using
      opioids to manage chronic non-cancer pain.
AB  - There has been a recent increase in public and professional concern about the
      prescription of strong prescription opioids for pain. Despite this concern,
      research to date has been limited because of a number of factors such as small
      sample sizes, exclusion of people with complex comorbidities, and studies of
      short duration. The Pain and Opioids IN Treatment is a 2-year prospective cohort
      study of 1500 people prescribed with pharmaceutical opioids for their chronic
      pain. This article provides an overview of the demographic and clinical
      characteristics of the cohort using the baseline data of 1514 community-based
      people across Australia. Participants had been in pain for a period of 10 years
      and had been on prescription opioids for approximately 4 years. One in 10 was on
      a daily morphine equivalent dose of >=200 mg. Employment and income levels were
      low, and two-thirds of the sample reported that their pain had impacted on their
      employment status. Approximately 50% screened positive for current moderate-to
      severe depression, and 1 in 5 had made a lifetime suicide attempt. There were a
      number of age-related differences. The younger groups experienced higher levels
      of pain and pain interference, more mental health and substance use issues, and
      barriers to treatment, compared with the older group. This study found that the
      people who have been prescribed strong opioids for chronic pain have very complex
      demographic and clinical profiles. Major age-related differences in the
      experiences of pain, coping, mental health, and substance use suggest the
      necessity of differential approaches to treatment. 

PMID- 25599446
TI  - National Breakthrough Pain Study: prevalence, characteristics, and associations
      with health outcomes.
AB  - The National Breakthrough Pain Study is a large observational study that assessed
      breakthrough pain (BTP) in a population of commercially insured community
      dwelling patients with opioid-treated chronic pain. Eligible patients were
      identified from an administrative claims database, and consenting patients were
      asked to complete a structured telephone interview and several validated
      questionnaires. Questionnaires assessed pain interference with function (Brief
      Pain Inventory-Short Form), health status (Short Form 12 [SF-12] Health Survey),
      disability (Sheehan Disability Scale), work performance (World Health
      Organization Health and Work Performance Questionnaire), and mood (Generalized
      Anxiety Disorder-7 Screener [GAD-7] and Patient Health Questionnaire-2 [PHQ-2]).
      Of 2198 patients interviewed, 1278 patients had persistent pain controlled with
      opioid therapy; 1023 (80%) of these patients reported BTP. Patients had a median
      of 2.0 episodes of BTP per day (range, 1-50) and a median duration of BTP of 45
      minutes (range, 1-720). Compared with patients without BTP, patients with BTP had
      more pain-related interference in function (Brief Pain Inventory, mean +/- SD:
      34.2 +/- 15.6 vs 25.0 +/- 15.7 [P < 0.001]), worse physical health (SF-12
      physical component score: 29.9 +/- 9.6 vs 35.1 +/- 10.4 [P < 0.001]) and mental
      health (SF-12 mental component score: 47.4 +/- 11.3 vs 49.3 +/- 10.4 [P <
      0.001]), more disability (Sheehan Disability Scale global impairment score: 15.1
      +/- 9.1 vs 10.6 +/- 8.5; World Health Organization Health and Work Performance
      Questionnaire absolute absenteeism: 12.4 +/- 59.9 vs 7.7 +/- 44.9 hours [both P <
      0.001]), and worse mood (GAD-7 score: 7.4 +/- 5.9 vs 5.9 +/- 5.4; PHQ-2 anhedonia
      score: 1.2 +/- 1.1 vs 0.9 +/- 1.0 [both P < 0.001]). In this population of
      community-dwelling patients with opioid-treated chronic pain, BTP was highly
      prevalent and associated with negative outcomes. This burden of illness suggests
      the need for specific treatment plans. 

PMID- 25599445
TI  - Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by
      opioids and baclofen.
AB  - Distinct subsets of sensory nerve fibres are involved in mediating mechanical and
      thermal pain hypersensitivity. They may also differentially respond to
      analgesics. Heat-sensitive C-fibres, for example, are thought to respond to MU
      opioid receptor (MOR) activation while mechanoreceptive fibres are supposedly
      sensitive to delta-opioid receptor (DOR) or GABAB receptor (GABABR) activation.
      The suggested differential distribution of inhibitory neurotransmitter receptors
      on different subsets of sensory fibres is, however, heavily debated. In this
      study, we quantitatively compared the degree of presynaptic inhibition exerted by
      opioids and the GABABR agonist baclofen on (1) vesicular glutamate transporter
      subtype 3-positive (VGluT3) non-nociceptive primary afferent fibres and (2)
      putative nociceptive C-fibres. To investigate VGluT3 sensory fibres, we evoked
      excitatory postsynaptic currents with blue light at the level of the dorsal root
      ganglion (DRG) in spinal cord slices of mice, expressing channelrhodopsin-2.
      Putative nociceptive C-fibres were explored in VGluT3-knockout mice through
      electrical stimulation. The MOR agonist DAMGO strongly inhibited both VGluT3 and
      VGluT3 C-fibres innervating lamina I neurons but generally had less influence on
      fibres innervating lamina II neurons. The DOR agonist SNC80 did not have any
      pronounced effect on synaptic transmission in any fibre type tested. Baclofen, in
      striking contrast, powerfully inhibited all fibre populations investigated. In
      summary, we report optogenetic stimulation of DRG neurons in spinal slices as a
      capable approach for the subtype-selective investigation of primary afferent
      nerve fibres. Overall, pharmacological accessibility of different subtypes of
      sensory fibres considerably overlaps, indicating that MOR, DOR, and GABABR
      expressions are not substantially segregated between heat and mechanosensitive
      fibres. 

PMID- 25599447
TI  - Deficient conditioned pain modulation after spinal cord injury correlates with
      clinical spontaneous pain measures.
AB  - The contribution of endogenous pain modulation dysfunction to clinical and
      sensory measures of neuropathic pain (NP) has not been fully explored.
      Habituation, temporal summation, and heterotopic noxious conditioning stimulus
      induced modulation of tonic heat pain intensity were examined in healthy
      noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in
      individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10).
      Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and
      phasic or tonic (30 seconds) heat pain intensity were assessed within the C6
      dermatome. Although habituation to tonic heat pain intensity (0-10) was reported
      by the noninjured (10 s: 3.5 +/- 0.3 vs 30 s: 2.2 +/- 0.5 numerical rating scale;
      P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 +/- 0.3
      vs 3.6 +/- 0.5) and SCI-NP group (4.2 +/- 0.4 vs 4.9 +/- 0.8). Significant
      temporal summation of tonic heat pain intensity was not observed in the 3 groups.
      Inhibition of tonic heat pain intensity induced by heterotopic noxious
      conditioning stimulus was identified in the noninjured (-29.7% +/- 9.7%) and SCI
      noNP groups (-19.6% +/- 7.0%), but not in subjects with SCI-NP (+1.1% +/- 8.0%; P
      < 0.05). Additionally, the mean conditioned pain modulation response correlated
      positively with Cz/AFz CHEP amplitude (rho = 0.8; P = 0.015) and evoked heat pain
      intensity (rho = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression
      analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated
      with pain severity and pressing spontaneous pain in the SCI-NP group.
      Comprehensive assessment of sensory dysfunction above the level of injury with
      tonic thermal test and conditioning stimuli revealed less-efficient endogenous
      pain modulation in subjects with SCI-NP. 

PMID- 25599448
TI  - Association of functional variations in COMT and GCH1 genes with postherniotomy
      pain and related impairment.
AB  - Persistent postoperative pain is a well-established clinical problem with
      potential severe personal and socioeconomic implications. The prevalence of
      persistent pain varies across surgery types. Severe persistent pain and related
      impairment occur in 5% to 10% of patients after groin hernia repair. The
      substantial interindividual variability in pain-related phenotypes within each
      surgery type cannot be explained by environmental factors alone, suggesting that
      genetic variation may play a role. We investigated the contribution of COMT and
      GCH1 to persistent postherniotomy pain (PPP)-related functional impairment.
      Prospective data from 429 Caucasian male patients with hernia were collected.
      Three COMT and 2 GCH1 tagging single-nucleotide polymorphisms (SNPs) were
      genotyped and analyzed for association with PPP-related activity impairment at 6
      months after herniotomy. Fifty-five (12.8%) patients had moderate-to-severe pain
      related activity impairment 6 months postoperatively as measured by Activity
      Assessment Scale (>=8.3). Patients with the G allele of COMT SNP rs6269 and C
      allele of COMT SNP rs4633 had less impairment (P = 0.03 and 0.01, respectively);
      in addition, the COMT haplotype GCG was associated with less impairment. For
      GCH1, the A allele of SNP rs3783641, T allele of rs8007267, and AT haplotype
      showed a protective effect trend (although nonsignificant; P = 0.08, 0.06, and
      0.08, respectively). A prediction model of substantial PPP-related activity
      impairment, combining COMT and GCH1 SNPs with clinical, psychophysical, and
      psychological risk factors, had a "good" (0.8 < area under curve < 0.9)
      discriminatory power. These data suggest that functional variations in COMT and
      GCH1 combined with clinical factors are predictive of PPP-related impairment
      after groin herniotomy. 

PMID- 25599450
TI  - Differential neurophysiological correlates of bottom-up and top-down modulations
      of pain.
AB  - The perception of pain is highly variable. It depends on bottom-up-mediated
      factors like stimulus intensity and top-down-mediated factors like expectations.
      In the brain, pain is associated with a complex pattern of neuronal responses
      including evoked potentials and induced responses at alpha and gamma frequencies.
      Although they all covary with stimulus intensity and pain perception, responses
      at gamma frequencies can be particularly closely related to the perception of
      pain. It is, however, unclear whether this association holds true across all
      types of pain modulation. Here, we used electroencephalography to directly
      compare bottom-up- and top-down-mediated modulations of pain, which were
      implemented by changes in stimulus intensity and placebo analgesia, respectively.
      The results show that stimulus intensity modulated pain-evoked potentials and
      pain-induced alpha and gamma responses. In contrast, placebo analgesia was
      associated with changes of evoked potentials, but not of alpha and gamma
      responses. These findings reveal that pain-related neuronal responses are
      differentially sensitive to bottom-up and top-down modulations of pain,
      indicating that they provide complementary information about pain perception. The
      results further show that pain-induced gamma oscillations do not invariably
      encode pain perception but may rather represent a marker of sensory processing
      whose influence on pain perception varies with behavioral context. 

PMID- 25599449
TI  - Effects of testosterone replacement in men with opioid-induced androgen
      deficiency: a randomized controlled trial.
AB  - Symptomatic androgen deficiency is common in patients taking opioid analgesics,
      as these drugs potently suppress the hypothalamic-pituitary-gonadal axis.
      However, the efficacy of testosterone replacement in this setting remains
      unclear. The objective of this trial was to evaluate the efficacy of testosterone
      replacement on pain perception and other androgen-dependent outcomes in men with
      opioid-induced androgen deficiency. We conducted a randomized, double-blind,
      parallel placebo-controlled trial at an outpatient academic research center.
      Participants were men aged 18 to 64 years on opioid analgesics for chronic
      noncancer pain, and total testosterone levels were <350 ng/dL. Participants were
      randomly assigned to 14 weeks of daily transdermal gel that contained 5 g of
      testosterone or placebo. Primary outcomes were changes in self-reported clinical
      pain and objectively assessed pain sensitivity. Sexual function, quality of life,
      and body composition were also assessed. The mean age was 49 years. The median
      total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and
      251 ng/dL and 43 pg/mL in the testosterone and placebo arm, respectively. Of the
      84 randomized participants, 65 had follow-up data on efficacy outcomes. Compared
      with men assigned to the placebo arm, those assigned to testosterone replacement
      experienced greater improvements in pressure and mechanical hyperalgesia, sexual
      desire, and role limitation due to emotional problems. Testosterone
      administration was also associated with an improvement in body composition. There
      were no between-group differences in changes in self-reported pain. In
      conclusion, in men with opioid-induced androgen deficiency, testosterone
      administration improved pain sensitivity, sexual desire, body composition, and
      aspects of quality of life. 

PMID- 25599451
TI  - Tumor necrosis factor inhibitor therapy in ankylosing spondylitis: differential
      effects on pain and fatigue and brain correlates.
AB  - Ankylosing spondylitis is associated with back pain and fatigue and impacts
      mobility but can be treated with tumor necrosis factor inhibitors (TNFi). The
      differential effects of TNFi treatment on multiple symptoms and the brain is not
      well delineated. Thus, we conducted a 2-part study. In study 1, we conducted a
      retrospective chart review in 129 ankylosing spondylitis patients to assess TNFi
      effects on pain, fatigue, motor function, mobility, and quality of life (QoL).
      After at least 10 weeks of TNFi treatment, patients had clinically significant
      improvements (>30%) in pain (including neuropathic pain), most disease and QoL
      factors, and normalized sensory detection thresholds. However, residual fatigue
      (mean = 5.3) was prominent. Although 60% of patients had significant relief of
      pain, only 22% of patients had significant relief of both pain and fatigue.
      Therefore, the preferential TNFi treatment effect on pain compared with fatigue
      could contribute to suboptimal effects on QoL. Part 2 was a prospective study in
      14 patients to identify TNFi treatment effects on pain, fatigue, sensory and
      psychological factors, and brain cortical thickness based on 3T magnetic
      resonance imaging. Centrally, TNFi was associated with statistically significant
      cortical thinning of motor, premotor, and posterior parietal regions. Pain
      intensity reduction was associated with cortical thinning of the secondary
      somatosensory cortex, and pain unpleasantness reduction was associated with the
      cortical thinning of motor areas. In contrast, fatigue reduction correlated with
      cortical thinning of the insula, primary sensory cortex/inferior parietal sulcus,
      and superior temporal polysensory areas. This indicates that TNFi treatment
      produces changes in brain areas implicated in sensory, motor, affective, and
      cognitive functions. 

PMID- 25599452
TI  - Selective melatonin MT2 receptor ligands relieve neuropathic pain through
      modulation of brainstem descending antinociceptive pathways.
AB  - Neuropathic pain is an important public health problem for which only a few
      treatments are available. Preclinical studies show that melatonin (MLT), a
      neurohormone acting on MT1 and MT2 receptors, has analgesic properties, likely
      through MT2 receptors. Here, we determined the effects of the novel selective MLT
      MT2 receptor partial agonist N-{2-([3-bromophenyl]-4
      fluorophenylamino)ethyl}acetamide (UCM924) in 2 neuropathic pain models in rats
      and examined its supraspinal mechanism of action. In rat L5-L6 spinal nerve
      ligation and spared nerve injury models, UCM924 (20-40 mg/kg, subcutaneously)
      produced a prolonged antinociceptive effect that is : (1) dose-dependent and
      blocked by the selective MT2 receptor antagonist 4-phenyl-2-propionamidotetralin,
      (2) superior to a high dose of MLT (150 mg/kg) and comparable with gabapentin
      (100 mg/kg), but (3) without noticeable motor coordination impairments in the
      rotarod test. Using double staining immunohistochemistry, we found that MT2
      receptors are expressed by glutamatergic neurons in the rostral ventrolateral
      periaqueductal gray. Using in vivo electrophysiology combined with tail flick, we
      observed that microinjection of UCM924 into the ventrolateral periaqueductal gray
      decreased tail flick responses, depressed the firing activity of ON cells, and
      activated the firing of OFF cells; all effects were MT2 receptor-dependent.
      Altogether, these data demonstrate that selective MT2 receptor partial agonists
      have analgesic properties through modulation of brainstem descending
      antinociceptive pathways, and MT2 receptors may represent a novel target in the
      treatment of neuropathic pain. 

PMID- 25599454
TI  - Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours
      by restoring spinal noradrenergic inhibitory tone.
AB  - The descending noradrenergic (NAergic) projection to the spinal cord forms part
      of an endogenous analgesic system. After nerve injury, a localised failure in
      this compensatory system has been implicated as a permissive factor in the
      development of neuropathic sensitisation. We investigated whether restoring
      descending NAergic tone with intrathecal reboxetine can oppose the development of
      the neuropathic pain phenotype after tibial nerve transection (TNT). Rats had a
      lumbar intrathecal catheter implanted at the time of nerve injury for
      administration of reboxetine (10 MUg) in both acute and chronic dosing
      experiments. In acute dosing experiments, both intrathecal and systemic (30
      mg/kg) reboxetine partially reversed mechanical allodynia. This antiallodynic
      effect of intrathecal reboxetine was blocked by prior administration of yohimbine
      (alpha2-adrenoceptor antagonist, 30 MUg) but not by prazosin (alpha1-adrenoceptor
      antagonist, 30 MUg) or propranolol (beta-adrenoceptor antagonist, 100 MUg).
      Chronic intrathecal reboxetine (10 MUg, intrathecally, twice daily for 2 weeks)
      suppressed the development of cold and mechanical allodynia. Nerve-injured
      animals demonstrated a place preference for intrathecal reboxetine, suggesting
      that it also reduced spontaneous pain. In contrast, an equivalent antiallodynic
      dose of systemic reboxetine (30 mg/kg) was aversive in both naive and TNT rats.
      On cessation of chronic intrathecal reboxetine, there was a gradual development
      of allodynic sensitisation that was indistinguishable from control TNT animals by
      7 days after the end of dosing. Our results suggest that pharmacological
      restoration of spinal NAergic tone with intrathecal reboxetine can suppress both
      allodynia and spontaneous pain in the TNT model. 

PMID- 25599453
TI  - Norepinephrine and dopamine transmission in 2 limbic regions differentially
      respond to acute noxious stimulation.
AB  - Central dopamine and norepinephrine regulate behavioral and physiological
      responses during rewarding and aversive stimuli. Here, we investigated and
      compared norepinephrine and dopamine transmission in 2 limbic structures, the
      ventral bed nucleus of the stria terminalis and the nucleus accumbens shell of
      anesthetized rats, respectively, in response to acute tail pinch, a noxious
      stimulus. Norepinephrine release in the ventral bed nucleus of the stria
      terminalis responded monophasically, increasing at the time of the tail pinch and
      remaining elevated for a period after its cessation. In contrast, dopamine
      transmission in the nucleus accumbens shell displayed a heterogeneous and time
      locked response to tail pinch. For most trials, there was a suppression of
      extracellular dopamine concentration throughout the duration of the stimuli. At
      the termination of the stimuli, however, extracellular dopamine either recovered
      back to or spiked above the initial baseline concentration. These signaling
      patterns were more clearly observed after administration of selective
      catecholamine autoreceptor and transporter inhibitors. The results suggest that
      the opposing responses of these catecholamines can provide integration of noxious
      inputs to influence behavioral outputs appropriate for survival such as escape or
      fighting. 

PMID- 25599455
TI  - Variability in opioid prescription monitoring and evidence of aberrant medication
      taking behaviors in urban safety-net clinics.
AB  - Little is known about variability in primary care providers' (PCPs) adherence to
      opioid-monitoring guidelines for patients. We examined variability of adherence
      to monitoring guidelines among PCPs and ascertained the relationship between PCP
      adherence and opioid misuse by their patients. We included primary care patients
      receiving long-term opioids (>=3 prescriptions within 6 months) for chronic
      noncancer pain and PCPs with >=4 eligible patients. We examined guideline
      adherence using: (1) electronic health record documentation of opioid treatment
      agreement, (2) past-year urine drug screen (UDS), and (3) evidence of misuse
      through early refills (>=2 opioid prescriptions written 7-25 days after the
      previous prescription). Covariates included morphine equivalent daily opioid
      medication dose (MED, >50 mg/d vs <=50mg/d). Multilevel regression models
      assessed variability among PCPs, and odds ratios examined associations among
      patient-level binary outcomes. Sixty-seven PCPs prescribed opioids to 1546
      patients. Significant variability was found between PCPs in use of agreement
      (variance = 1.27, P < 0.001), UDS (variance = 1.75, P < 0.001), and early refills
      (variance = 0.29, P = 0.002). Primary care providers had a mean of 48% of
      patients with agreement (range, 9%-84%), 56% with >=1 UDS (range, 7%-91%) and 36%
      with early refills (range, 19%-60%). High MED among patients was associated with
      increased odds of agreement (1.93, confidence interval [CI], 1.53-2.44), UDS
      (2.65, CI: 2.06-3.41), and early refill (2.92, CI: 2.30-3.70). Primary care
      providers varied significantly in adherence to opioid prescription guidelines.
      Increased patient risk was associated with increased monitoring and with greater
      misuse. Future work should study system-level interventions to enable clinical
      monitoring and support opioid guideline adherence. 

PMID- 25599457
TI  - Change in opioid dose and change in depression in a longitudinal primary care
      patient cohort.
AB  - Depression is associated with receipt of higher doses of prescription opioids. It
      is not known whether the reverse association exists in that an increased opioid
      dose is associated with increased depression. Questionnaires were administered to
      355 patients with chronic low back pain at baseline and 1-year and 2-year follow
      up. Depression, pain, anxiety, health-related quality of life, and social support
      or stress were obtained by survey. Opioid type and dose and comorbid conditions
      were derived from chart abstraction. Random intercept, generalized linear mixed
      models were computed to estimate the association between change in opioid
      morphine equivalent dose (MED) thresholds (0, 1-50, >50 mg) and probability of
      depression over time. Second, we computed the association between change in
      depression and odds of an increasing MED over time. After adjusting for
      covariates, an increase to >50 mg MED from nonuse increased a participant's
      probability of depression over time (odds ratio [OR] = 2.65; 95% confidence
      interval [CI], 1.17-5.98). An increase to 1 to 50 mg MED did not increase an
      individual's probability of depression over time (OR = 1.08; 95% CI, 0.65-1.79).
      In unadjusted analysis, developing depression was associated with a 2.13 (95% CI,
      1.36-3.36) increased odds of a higher MED. This association decreased after
      adjusting for all covariates (OR = 1.65; 95% CI, 0.97-2.81). Post hoc analysis
      revealed that depression was significantly associated with a 10.1-mg MED increase
      in fully adjusted models. Change to a higher MED leads to an increased risk of
      depression, and developing depression increases the likelihood of a higher MED.
      We speculate that treating depression or lowering MED may mitigate a
      bidirectional association and ultimately improve pain management. 

PMID- 25599459
TI  - Warty Dyskeratoma as a Cutaneous Horn of the Mons Pubis.

PMID- 25599456
TI  - Endocannabinoids and acute pain after total knee arthroplasty.
AB  - Osteoarthritis (OA) of the knee is a progressive disease that is associated with
      inflammation of the joints and lower extremity pain. Total knee arthroplasty
      (TKA) is a surgical procedure that aims to reduce pain and restore motor function
      in patients suffering from OA. The immediate postoperative period can be
      intensely painful leading to extended recovery times including persistent pain.
      The endocannabinoid system regulates nociception, and the activation of
      cannabinoid receptors produces antinociceptive effects in preclinical models of
      OA. To date, the influence of the endocannabinoid tone on pain and disability in
      OA patients and on acute postoperative pain in humans has not been explored. In
      this study, we provide the first comprehensive profile of endocannabinoids in
      serum, cerebrospinal fluid, and synovial fluid of patients with painful end-stage
      OA undergoing TKA and examine correlations between endocannabinoid levels,
      interleukin 6, functional disability, acute postoperative pain, and postoperative
      opioid use. Our results reveal that central (cerebrospinal fluid) and peripheral
      (synovial fluid) levels of the endocannabinoid 2-arachidonoyl glycerol were
      significantly elevated in patients who developed higher postoperative pain after
      TKA. In addition, synovial fluid 2-arachidonoyl glycerol levels were positively
      correlated with postoperative opioid use. Similarly, synovial fluid levels of the
      anti-inflammatory lipid palmitoylethanolamide correlated with functional
      disability in OA. Taken together, our results are the first to reveal
      associations between central and peripheral endocannabinoid levels and
      postoperative pain. This suggests that endocannabinoid metabolism may serve as a
      target for the development of novel analgesics both for systemic or local
      delivery into the joint. 

PMID- 25599458
TI  - The nocebo effect might affect treatment expectations in patients with burning
      mouth syndrome.

PMID- 25599460
TI  - Low Risk for Switch to Mania during Treatment with Sleep Promoting
      Antidepressants.
AB  - INTRODUCTION: Sleep-promoting antidepressants are of interest because they are
      used not only as antidepressants, but also to promote sleep. METHODS: We reviewed
      case reports describing the switch to mania during treatment with trazodone,
      mirtazapine, or agomelatine. RESULTS: Trazodone, mirtazapine, and agomelatine may
      induce manic symptoms. However, the risk of switching is related, first of all,
      to doses recommended for antidepressant treatment, administered without mood
      stabilizer co-therapy. Low doses of these antidepressants, used for their
      hypnotic or sedative effects, were observed to cause mania only in patients with
      other risk factors for switching. There is no evidence for trazodone or
      mirtazapine and only sparse evidence for agomelatine, claiming that treatment
      with these antidepressants is related to an increased risk of switching to mania
      when administered in combination with a mood stabilizer. DISCUSSION: These
      findings suggest that low doses of trazodone and mirtazapine are safe in bipolar
      disorder, and should still be considered important alternatives to hypnotics when
      long-term pharmacological treatment of insomnia is necessary. It seems that these
      antidepressants and agomelatine can also be used safely in antidepressant doses
      when combined with a mood stabilizer.

PMID- 25599461
TI  - The epidemiologic data on falls, 1998-2010: more older Americans report falling.

PMID- 25599462
TI  - Practical science and the science of practice: Critical Care Medicine, 2015.

PMID- 25599464
TI  - Postoperative pro-adrenomedullin levels predict mortality in thoracic surgery
      patients: comparison with Acute Physiology and Chronic Health Evaluation IV
      Score*.
AB  - OBJECTIVES: Risk assessment in ICU patients using commonly used prognostic models
      may be influenced using different data definitions and by errors in data
      collection. We investigated whether a set of biomarkers (procalcitonin, MR-pro
      adrenomedullin, CT-pro-endothelin-1, CT-pro-arginine vasopressin, and MR-pro
      atrial natriuretic peptide), alone or as a panel, could be useful in
      postoperative risk assessment for hospital mortality in comparison with the Acute
      Physiology and Chronic Health Evaluation IV score. DESIGN: In a prospective
      observational cohort study, we analyzed 800 consecutive patients undergoing
      elective cardiac surgery. We assessed biomarker levels on admission to the ICU
      and every 6 hours thereafter for 24 hours. For every postoperative time point and
      for every biomarker, we determined the predictive value for hospital mortality
      and made a comparison with the Acute Physiology and Chronic Health Evaluation IV
      score. SETTING: Intensive care of an academic referral hospital. PATIENTS: A
      total of 800 consecutive patients undergoing elective cardiac surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MR-pro-adrenomedullin is a
      good predictor of mortality (c-statistic at time point 6 hr after admission to
      the ICU, 0.940; 95% CI, 0.918-0.956) and performed better than the Acute
      Physiology and Chronic Health Evaluation IV score (c-statistic, 0.842; 95% CI,
      0.811-0.868). The c-statistic did not change significantly on the time points 6,
      12, and 18 hours after admission. Using a cutoff value for proadrenomedullin
      taken 6 hours after admission on ICU (time point 2) of 3.2 nmol/L sensitivity was
      81.8% and specificity 93.9%, the positive likelihood ratio was 13.3, positive
      predictive value was 31.0%, and negative predictive value was 99.4%. Patients
      with a MR-pro-adrenomedullin above this cutoff level had an odds ratio of 68.9
      (95% CI, 22.2-213.1) for not surviving their hospital stay. The other biomarkers
      had less predictive power. CONCLUSIONS: In elective cardiac surgery, MR-pro
      adrenomedullin measured between 6 and 18 hours after admission to the ICU is a
      better predictor of hospital mortality in comparison with the Acute Physiology
      and Chronic Health Evaluation IV score.

PMID- 25599465
TI  - Severe sepsis in hematopoietic stem cell transplant recipients*.
AB  - OBJECTIVE: Severe sepsis requires timely management and has high mortality if
      care is delayed. Hematopoietic stem cell transplant recipients are more likely to
      be immunocompromised and are predisposed to serious infections. Reports of
      outcomes of severe sepsis in this population are limited to data from single,
      tertiary care centers, and national outcomes data are missing. DESIGN:
      Retrospective analysis of an administrative database. SETTING: Twenty percent of
      community hospitals in United States, excluding federal hospitals. SUBJECT:
      Patients with severe sepsis. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS:
      We used International Classification of Diseases, 9th Edition, Clinical
      Modification codes indicating the presence of sepsis and organ system failure to
      identify hospitalizations for severe sepsis between 2000 and 2008. We also used
      International Classification of Diseases, 9th Edition, Clinical Modification
      codes to identify hematopoietic stem cell transplant recipients. We compared
      outcomes of hematopoietic stem cell transplant recipients with severe sepsis
      during engraftment and subsequent admissions with a non-hematopoietic stem cell
      transplant cohort and excluded solid-organ transplantation from this cohort. We
      used mixed effect, multivariate logistic regression modeling with propensity
      score adjustment to examine factors associated with mortality of severe sepsis in
      hematopoietic stem cell transplant recipients. A total of 21,898 hematopoietic
      stem cell transplant recipients with severe sepsis were identified. The frequency
      of severe sepsis in hematopoietic stem cell transplant recipients was five times
      higher when compared with the non-hematopoietic stem cell transplant cohort. The
      unadjusted mortality was 32.9% in non-hematopoietic stem cell transplant cohort,
      which was similar to autologous hematopoietic stem cell transplant recipients
      (30.1%) and those who did not develop graft-versus-host disease (35%). Mortality
      was significantly higher in allogeneic transplants (55.1%, p < 0.001) and in
      those who developed graft-versus-host disease (47.9%, p < 0.001). After
      adjustment, during engraftment admission, the odds of in-hospital mortality in
      allogeneic hematopoietic stem cell transplant (odds ratio, 3.81; 95% CI, 2.39
      6.07) and autologous hematopoietic stem cell transplant (odds ratio, 1.28; 95%
      CI, 1.06-1.53) recipients was significantly higher than non-hematopoietic stem
      cell transplant patients. Similarly, in subsequent admissions, hematopoietic stem
      cell transplant recipients with graft-versus-host disease (odds ratio, 2.14; 95%
      CI, 1.88-2.45) and without graft-versus-host disease (odds ratio, 1.35; 95% CI,
      1.19-1.54) had significantly higher odds of mortality than non-hematopoietic stem
      cell transplant patients. Among patients with hematopoietic stem cell transplant,
      persons with autologous hematopoietic stem cell transplant and those without
      graft-versus-host disease fared better as compared with their allogeneic and
      graft-versus-host disease counterparts. CONCLUSIONS: Hematopoietic stem cell
      transplant recipients are more likely to develop severe sepsis and die following
      a severe sepsis episode than nontransplant patients. Autologous hematopoietic
      stem cell transplant recipients and those who do not develop graft-versus-host
      disease have significantly better outcomes than allogeneic and graft-versus-host
      disease patients.

PMID- 25599466
TI  - Is copeptin level associated with 1-year mortality after out-of-hospital cardiac
      arrest? Insights from the Paris registry*.
AB  - OBJECTIVES: The availability of circulating biomarkers that helps to identify
      early out-of-hospital cardiac arrest survivors who are at increased risk of long
      term mortality remains challenging. Our aim was to prospectively study the
      association between copeptin and 1-year mortality in patients with out-of
      hospital cardiac arrest admitted in a tertiary cardiac arrest center. DESIGN:
      Retrospective monocenter study. SETTING: Tertiary cardiac arrest center in Paris,
      France. PATIENTS: Copeptin was assessed at admission and day 3. Pre- and
      intrahospital factors associated with 1-year mortality were analyzed by
      multivariate Cox proportional analysis. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Two hundred ninety-eight consecutive out-of-hospital cardiac arrest
      patients (70.3% male; median age, 60.2 yr [49.9-71.4]) were admitted in a
      tertiary cardiac arrest center in Paris (France). After multivariate analysis,
      higher admission copeptin was associated with 1-year mortality with a threshold
      effect (hazard ratio(5th vs 1st quintile) = 1.64; 95% CI, 1.05-2.58; p = 0.03).
      Day 3 copeptin was associated with 1-year mortality in a dose-dependent manner
      (hazard ratio(2nd vs 1st quintile) = 1.87; 95% CI, 1.00-3.49; p = 0.05; hazard
      ratio(3rd vs 1st quintile) = 1.92; 95% CI, 1.02-3.64; p = 0.04; hazard ratio(4th
      vs 1st quintile) = 2.12; 95% CI, 1.14-3.93; p = 0.02; and hazard ratio(5th vs 1st
      quintile) = 2.75; 95% CI, 1.47-5.15; p < 0.01; p for trend < 0.01). For both
      admission and day 3 copeptin, association with 1-year mortality existed for out
      of-hospital cardiac arrest of cardiac origin only (p for interaction = 0.05 and <
      0.01, respectively). When admission and day 3 copeptin were mutually adjusted,
      only day 3 copeptin remained associated with 1-year mortality in a dose-dependent
      manner (p for trend = 0.01). CONCLUSION: High levels of copeptin were associated
      with 1-year mortality independently from prehospital and intrahospital risk
      factors, especially in out-of-hospital cardiac arrest of cardiac origin. Day 3
      copeptin was superior to admission copeptin: this could permit identification of
      out-of-hospital cardiac arrest survivors at increased risk of mortality and allow
      for close observation of such patients.

PMID- 25599467
TI  - Early and late unplanned rehospitalizations for survivors of critical illness*.
AB  - OBJECTIVES: Preventing rehospitalizations for patients with serious chronic
      illnesses is a focus of national quality initiatives. Although 8 million people
      are admitted yearly to an ICU, the frequency of rehospitalizations (readmissions
      to the hospital after discharge) is unknown. We sought to determine the frequency
      of rehospitalization after an ICU stay, outcomes for rehospitalized patients, and
      factors associated with rehospitalization. DESIGN: Retrospective cohort study
      using the New York Statewide Planning and Research Cooperative System, an
      administrative database of all hospital discharges in New York State. SETTING:
      ICUs in New York State. PATIENTS: ICU patients who survived to hospital discharge
      in 2008-2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome
      was the cumulative incidence of first early rehospitalization (within 30 days of
      discharge), and secondary outcome was the cumulative incidence of late
      rehospitalization (between 31 and 180 d). Factors associated with
      rehospitalization within both time periods were identified using competing risk
      regression models. Of 492,653 ICU patients, 79,960 had a first early
      rehospitalization (cumulative incidence, 16.2%) and an additional 73,250 late
      rehospitalizations (cumulative incidence, 18.9%). Over one quarter of all
      rehospitalizations (28.6% for early; 26.7% for late) involved ICU admission.
      Overall hospital mortality for rehospitalized patients was 7.6% for early and
      4.6% for late rehospitalizations. Longer index hospitalization (adjusted hazard
      ratio, 1.61; 95% CI, 1.57-1.66 for 7-13 d vs < 3 d), discharge to a skilled
      nursing facility versus home (adjusted hazard ratio, 1.54; 95% CI, 1.51-1.58),
      and having metastatic cancer (adjusted hazard ratio, 1.46; 95% CI, 1.41-1.51)
      were associated with the greatest hazard of early rehospitalization. CONCLUSIONS:
      Approximately 16% of ICU survivors were rehospitalized within 30 days of hospital
      discharge; rehospitalized patients had high rates of ICU admission and hospital
      mortality. Few characteristics were strongly associated with rehospitalization,
      suggesting that identifying high-risk individuals for intervention may require
      additional predictors beyond what is available in administrative databases.

PMID- 25599468
TI  - Out-of-hospital cardiac arrest from brain cause: epidemiology, clinical features,
      and outcome in a multicenter cohort*.
AB  - OBJECTIVES: Although sudden cardiac death has been broadly studied, little is
      known on cerebrovascular events revealed by out-of-hospital cardiac arrest. We
      aimed to describe clinical features and prognosis of these patients and identify
      characteristics that could suggest a cerebrovascular etiology of the out-of
      hospital cardiac arrest. DESIGN: Retrospective review (1999-2012) of databases of
      three regional referral ICU centers for out-of-hospital cardiac arrest. SETTING:
      Patients admitted to ICU for management of successfully resuscitated out-of
      hospital cardiac arrest. PATIENTS: Patients were included when subarachnoid
      hemorrhage, intracranial hemorrhage, ischemic stroke, sub/epidural hematoma, or
      cerebral thrombophlebitis was identified as the primary cause of out-of-hospital
      cardiac arrest. Traumatic or infectious causes were excluded. Patients were
      compared with a group of out-of-hospital cardiac arrest of nonneurological
      origin. INTERVENTIONS: All medical records of the three prospective ICU
      databases, registered according to the Utstein style, were reviewed. MEASUREMENTS
      AND MAIN RESULTS: Among 3,710 patients admitted for out-of-hospital cardiac
      arrest, 86 were included (mainly subarachnoid hemorrhage, n = 73). Prodromes were
      mostly neurological but falsely evoked a cardiac origin in six patients.
      Electrocardiogram displayed abnormalities in 64% of patients, with 23% of
      pseudoischemic pattern (ST-segment elevation or left bundle branch block).
      Mortality rate was 100%, with brain death as the leading cause. In comparison
      with the nonneurological out-of-hospital cardiac arrest group, female gender,
      onset of neurological prodromes, lack of other prodromes, initial nonshockable
      rhythm, and unspecific electrocardiogram repolarization abnormalities were
      independent predictive factors of a primary cerebrovascular etiology. When
      present, the combination of these elements displayed an area under the receiver
      operating characteristic curve of 0.86 (95% CI, 0.81-0.91). CONCLUSIONS:
      Presentation of cerebrovascular event complicated with out-of-hospital cardiac
      arrest may mimic coronary etiology, but several clinical elements may help to
      identify brain causes. Even if survival is null, the high proportion of brain
      deaths provides opportunity for organ donation.

PMID- 25599469
TI  - The pitfalls of benchmarking ICUs*.

PMID- 25599470
TI  - Nonbeneficial care: we have got to do something?*.

PMID- 25599463
TI  - Fluid management with a simplified conservative protocol for the acute
      respiratory distress syndrome*.
AB  - OBJECTIVES: In the Fluid and Catheter Treatment Trial (FACTT) of the National
      Institutes of Health Acute Respiratory Distress Syndrome Network, a conservative
      fluid protocol (FACTT Conservative) resulted in a lower cumulative fluid balance
      and better outcomes than a liberal fluid protocol (FACTT Liberal). Subsequent
      Acute Respiratory Distress Syndrome Network studies used a simplified
      conservative fluid protocol (FACTT Lite). The objective of this study was to
      compare the performance of FACTT Lite, FACTT Conservative, and FACTT Liberal
      protocols. DESIGN: Retrospective comparison of FACTT Lite, FACTT Conservative,
      and FACTT Liberal. Primary outcome was cumulative fluid balance over 7 days.
      Secondary outcomes were 60-day adjusted mortality and ventilator-free days
      through day 28. Safety outcomes were prevalence of acute kidney injury and new
      shock. SETTING: ICUs of Acute Respiratory Distress Syndrome Network participating
      hospitals. PATIENTS: Five hundred three subjects managed with FACTT Conservative,
      497 subjects managed with FACTT Liberal, and 1,124 subjects managed with FACTT
      Lite. INTERVENTIONS: Fluid management by protocol. MEASUREMENTS AND MAIN RESULTS:
      Cumulative fluid balance was 1,918 +/- 323 mL in FACTT Lite, -136 +/- 491 mL in
      FACTT Conservative, and 6,992 +/- 502 mL in FACTT Liberal (p < 0.001). Mortality
      was not different between groups (24% in FACTT Lite, 25% in FACTT Conservative
      and Liberal, p = 0.84). Ventilator-free days in FACTT Lite (14.9 +/- 0.3) were
      equivalent to FACTT Conservative (14.6 +/- 0.5) (p = 0.61) and greater than in
      FACTT Liberal (12.1 +/- 0.5, p < 0.001 vs Lite). Acute kidney injury prevalence
      was 58% in FACTT Lite and 57% in FACTT Conservative (p = 0.72). Prevalence of new
      shock in FACTT Lite (9%) was lower than in FACTT Conservative (13%) (p = 0.007 vs
      Lite) and similar to FACTT Liberal (11%) (p = 0.18 vs Lite). CONCLUSIONS: FACTT
      Lite had a greater cumulative fluid balance than FACTT Conservative but had
      equivalent clinical and safety outcomes. FACTT Lite is an alternative to FACTT
      Conservative for fluid management in Acute Respiratory Distress Syndrome.

PMID- 25599471
TI  - Chronic critical illness: a growing legacy of successful advances in critical
      care*.

PMID- 25599472
TI  - Fluid therapy during acute respiratory distress syndrome: less is more,
      simplified*.

PMID- 25599473
TI  - Sepsis survivorship: how can we promote a culture of resilience?

PMID- 25599474
TI  - Predicting outcome in acute respiratory distress syndrome-putting some science
      behind crystal gazing*.

PMID- 25599475
TI  - Cooling is hard on the heart: which dose after cardiac arrest?

PMID- 25599476
TI  - Enrolling patients into multiple trials: it is time for glasnost*.

PMID- 25599477
TI  - Critically ill patients with H7N9: new virus, old challenges*.

PMID- 25599478
TI  - The PaO2/FIO2 ratio categorization of patients with acute respiratory distress
      syndrome is suboptimal*.

PMID- 25599479
TI  - Hospital readmission after acute kidney injury--why?*.

PMID- 25599480
TI  - Dysphagia diagnosed by fiberoptic endoscopy is common and transient in critical
      illness polyneuropathy: are there any clinical implications?

PMID- 25599481
TI  - Predicting mortality after elective open-heart surgery using midregional
      proadrenomedullin: is it time to scalp Acute Physiology and Chronic Health
      Evaluation IV?

PMID- 25599482
TI  - Choosing between methods to prevent methicillin-resistant Staphylococcus aureus
      in ICUs*.

PMID- 25599483
TI  - Paring Down cytomegalovirus's role in acute respiratory distress syndrome
      outcome*.

PMID- 25599484
TI  - Is it time for individualized thromboprophylaxis regimens in the ICU?

PMID- 25599485
TI  - Sepsis: a persistent threat following hematopoietic stem cell transplantation*.

PMID- 25599486
TI  - Prediction of mortality from out-of-hospital cardiac arrest is key to decrease
      morbidity and mortality from cardiac, neurologic, and other major organ damage*.

PMID- 25599487
TI  - Readmission after intensive care: frequent, hazardous, and possibly preventable*.

PMID- 25599488
TI  - Prediction is very difficult, especially about the future*.

PMID- 25599489
TI  - Multimodal monitoring after traumatic brain injury: useless or useful?

PMID- 25599490
TI  - Out-of-hospital cardiac arrest from neurologic cause: recognition and outcome*.

PMID- 25599492
TI  - Catatonia in the ICU.

PMID- 25599493
TI  - The authors reply.

PMID- 25599494
TI  - Association of renal dysfunction with mortality following cardiac surgery.

PMID- 25599491
TI  - Inhibition of the mitochondrial fission protein dynamin-related protein 1
      improves survival in a murine cardiac arrest model.
AB  - OBJECTIVES: Survival following sudden cardiac arrest is poor despite advances in
      cardiopulmonary resuscitation and the use of therapeutic hypothermia. Dynamin
      related protein 1, a regulator of mitochondrial fission, is an important
      determinant of reactive oxygen species generation, myocardial necrosis, and left
      ventricular function following ischemia/reperfusion injury, but its role in
      cardiac arrest is unknown. We hypothesized that dynamin-related protein 1
      inhibition would improve survival, cardiac hemodynamics, and mitochondrial
      function in an in vivo model of cardiac arrest. DESIGN: Laboratory investigation.
      SETTING: University laboratory. INTERVENTIONS: Anesthetized and ventilated adult
      female C57BL/6 wild-type mice underwent an 8-minute KCl-induced cardiac arrest
      followed by 90 seconds of cardiopulmonary resuscitation. Mice were then blindly
      randomized to a single IV injection of Mdivi-1 (0.24 mg/kg), a small molecule
      dynamin-related protein 1 inhibitor or vehicle (dimethyl sulfoxide). MEASUREMENTS
      AND MAIN RESULTS: Following resuscitation from cardiac arrest, mitochondrial
      fission was evidenced by dynamin-related protein 1 translocation to the
      mitochondrial membrane and a decrease in mitochondrial size. Mitochondrial
      fission was associated with increased lactate and evidence of oxidative damage.
      Mdivi-1 administration during cardiopulmonary resuscitation inhibited dynamin
      related protein 1 activation, preserved mitochondrial morphology, and decreased
      oxidative damage. Mdivi-1 also reduced the time to return of spontaneous
      circulation (116 +/- 4 vs 143 +/- 7 s; p < 0.001) during cardiopulmonary
      resuscitation and enhanced myocardial performance post-return of spontaneous
      circulation. These improvements were associated with significant increases in
      survival (65% vs 33%) and improved neurological scores up to 72 hours post
      cardiac arrest. CONCLUSIONS: Post-cardiac arrest inhibition of dynamin-related
      protein 1 improves time to return of spontaneous circulation and myocardial
      hemodynamics, resulting in improved survival and neurological outcomes in a
      murine model of cardiac arrest. Pharmacological targeting of mitochondrial
      fission may be a promising therapy for cardiac arrest.

PMID- 25599495
TI  - The authors reply.

PMID- 25599496
TI  - Does chlorhexidine-impregnated dressing reduce the risk of catheter-related
      bloodstream infection in all vascular access?

PMID- 25599497
TI  - The authors reply.

PMID- 25599498
TI  - The authors reply.

PMID- 25599499
TI  - Heart-lung interactions: have a look on the superior vena cava and on the changes
      in right ventricular afterload.

PMID- 25599500
TI  - The authors reply.

PMID- 25599501
TI  - Chest wall elastance in the estimation of the transpulmonary pressure: how should
      we use it?

PMID- 25599502
TI  - The authors reply.

PMID- 25599503
TI  - Prone positioning in acute respiratory distress syndrome.

PMID- 25599504
TI  - The authors reply.

PMID- 25599505
TI  - Chronic critical illness should be considered in long-term mortality study among
      critical illness patients.

PMID- 25599506
TI  - The authors reply.

PMID- 25599507
TI  - Of course, futile care is wasteful--are we ready to act on this knowledge?

PMID- 25599508
TI  - The authors reply.

PMID- 25599509
TI  - Ventilator-associated events: a broader perspective.

PMID- 25599510
TI  - The authors reply.

PMID- 25599511
TI  - The influence of partner's behavior on health behavior change: the English
      Longitudinal Study of Ageing.
AB  - IMPORTANCE: Couples are highly concordant for unhealthy behaviors, and a change
      in one partner's health behavior is often associated with a change in the other
      partner's behavior. However, no studies have explicitly compared the influence of
      having a partner who takes up healthy behavior (eg, quits smoking) with one whose
      behavior is consistently healthy (eg, never smokes). OBJECTIVE: To examine the
      influence of partner's behavior on making positive health behavior changes.
      DESIGN, SETTING, AND PARTICIPANTS: We used prospective data from married and
      cohabiting couples (n, 3722) participating in the English Longitudinal Study of
      Ageing, a large population-based cohort of older adults (>=50 years). Studying
      men and women who had unhealthy behaviors in 3 domains at baseline (ie, smoking,
      physically inactive, or overweight/obese), we used logistic regression analysis
      to examine the influence of the partner's behavior in the same domain on the odds
      of positive health behavior change over time. MAIN OUTCOMES AND MEASURES: Smoking
      cessation, increased physical activity, and 5% weight loss or greater. RESULTS:
      Across all domains, we found that when one partner changed to a healthier
      behavior (newly healthy), the other partner was more likely to make a positive
      health behavior change than if their partner remained unhealthy (smoking: men 48%
      vs 8%, adjusted odds ratio [OR], 11.82 [95% CI, 4.84-28.90]; women 50% vs 8%, OR,
      11.23 [4.58-27.52]) (physical activity: men 67% vs 26%, OR, 5.28 [3.70-7.54];
      women 66% vs 24%, OR, 5.36 [3.74-7.68]) (weight loss: men 26% vs 10%, OR, 3.05
      [1.96-4.74]; women 36% vs 15%, OR, 3.08 [1.98-4.80]). For smoking and physical
      activity, having a consistently healthy partner also predicted positive change,
      but for each domain, the odds were significantly higher in individuals with a
      newly healthy partner than those with a consistently healthy partner (smoking:
      men OR, 3.08 [1.43-6.62]; women OR, 5.45 [2.44-12.16]) (physical activity: men
      OR, 1.92 [1.37-2.70]; women OR, 1.84 [1.33-2.53]) (weight loss: men OR, 2.28
      [1.36-3.84]; women OR, 2.86 [1.55-5.26]). CONCLUSIONS AND RELEVANCE: Men and
      women are more likely to make a positive health behavior change if their partner
      does too, and with a stronger effect than if the partner had been consistently
      healthy in that domain. Involving partners in behavior change interventions may
      therefore help improve outcomes.

PMID- 25599512
TI  - Testing before seeing the patient.

PMID- 25599513
TI  - The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK
      NHS Breast Screening Programme--a multicentre retrospective reading study
      comparing the diagnostic performance of digital breast tomosynthesis and digital
      mammography with digital mammography alone.
AB  - BACKGROUND: Digital breast tomosynthesis (DBT) is a three-dimensional mammography
      technique with the potential to improve accuracy by improving differentiation
      between malignant and non-malignant lesions. OBJECTIVES: The objectives of the
      study were to compare the diagnostic accuracy of DBT in conjunction with two
      dimensional (2D) mammography or synthetic 2D mammography, against standard 2D
      mammography and to determine if DBT improves the accuracy of detection of
      different types of lesions. STUDY POPULATION: Women (aged 47-73 years) recalled
      for further assessment after routine breast screening and women (aged 40-49
      years) with moderate/high of risk of developing breast cancer attending annual
      mammography screening were recruited after giving written informed consent.
      INTERVENTION: All participants underwent a two-view 2D mammography of both
      breasts and two-view DBT imaging. Image-processing software generated a synthetic
      2D mammogram from the DBT data sets. RETROSPECTIVE READING STUDY: In an
      independent blinded retrospective study, readers reviewed (1) 2D or (2) 2D + DBT
      or (3) synthetic 2D + DBT images for each case without access to original
      screening mammograms or prior examinations. Sensitivities and specificities were
      calculated for each reading arm and by subgroup analyses. RESULTS: Data were
      available for 7060 subjects comprising 6020 (1158 cancers) assessment cases and
      1040 (two cancers) family history screening cases. Overall sensitivity was 87%
      [95% confidence interval (CI) 85% to 89%] for 2D only, 89% (95% CI 87% to 91%)
      for 2D + DBT and 88% (95% CI 86% to 90%) for synthetic 2D + DBT. The difference
      in sensitivity between 2D and 2D + DBT was of borderline significance (p = 0.07)
      and for synthetic 2D + DBT there was no significant difference (p = 0.6).
      Specificity was 58% (95% CI 56% to 60%) for 2D, 69% (95% CI 67% to 71%) for 2D +
      DBT and 71% (95% CI 69% to 73%) for synthetic 2D + DBT. Specificity was
      significantly higher in both DBT reading arms for all subgroups of age, density
      and dominant radiological feature (p < 0.001 all cases). In all reading arms,
      specificity tended to be lower for microcalcifications and higher for
      distortion/asymmetry. Comparing 2D + DBT to 2D alone, sensitivity was
      significantly higher: 93% versus 86% (p < 0.001) for invasive tumours of size 11
      20 mm. Similarly, for breast density 50% or more, sensitivities were 93% versus
      86% (p = 0.03); for grade 2 invasive tumours, sensitivities were 91% versus 87%
      (p = 0.01); where the dominant radiological feature was a mass, sensitivities
      were 92% and 89% (p = 0.04) For synthetic 2D + DBT, there was significantly (p =
      0.006) higher sensitivity than 2D alone in invasive cancers of size 11-20 mm,
      with a sensitivity of 91%. CONCLUSIONS: The specificity of DBT and 2D was better
      than 2D alone but there was only marginal improvement in sensitivity. The
      performance of synthetic 2D appeared to be comparable to standard 2D. If these
      results were observed with screening cases, DBT and 2D mammography could benefit
      to the screening programme by reducing the number of women recalled
      unnecessarily, especially if a synthetic 2D mammogram were used to minimise
      radiation exposure. Further research is required into the feasibility of
      implementing DBT in a screening setting, prognostic modelling on outcomes and
      mortality, and comparison of 2D and synthetic 2D for different lesion types.
      STUDY REGISTRATION: Current Controlled Trials ISRCTN73467396. FUNDING: This
      project was funded by the NIHR Health Technology Assessment programme and will be
      published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA
      programme website for further project information.

PMID- 25599514
TI  - PGluS: prediction of protein S-glutathionylation sites with multiple features and
      analysis.
AB  - S-Glutathionylation is a reversible protein post-translational modification,
      which generates mixed disulfides between glutathione (GSH) and cysteine residues,
      playing an important role in regulating protein stability, activity, and redox
      regulation. To fully understand S-glutathionylation mechanisms, identification of
      substrates and specific S-glutathionylated sites is crucial. Compared with the
      labor-intensive and time-consuming experimental approaches, computational
      predictions of S-glutathionylated sites are very desirable due to their
      convenience and high speed. Therefore, in this study, a new bioinformatics tool
      named PGluS was developed to predict S-glutathionylated sites based on multiple
      features and support vector machines. The performance of PGluS was measured with
      an accuracy of 71.41% and a MCC of 0.431 using the 5-fold cross-validation on the
      training dataset. Additionally, PGluS was evaluated using an independent testing
      dataset resulting in an accuracy of 71.25%, which demonstrated that PGluS was
      very promising for predicting S-glutathionylated sites. Furthermore, feature
      analysis was performed and it was shown that all features adopted in this method
      contributed to the S-glutathionylation process. A site-specific analysis showed
      that S-glutathionylation was intimately correlated with the features derived from
      its surrounding sites. The conclusions derived from this study might help to
      understand more of the S-glutathionylation mechanism and guide the related
      experimental validation. For public access, PGluS is freely accessible at . 

PMID- 25599515
TI  - Playing Together: The Physical Activity Beliefs and Behaviors of Urban Aboriginal
      Youth.
AB  - BACKGROUND: Urban Aboriginal youth are a rapidly growing segment of the Canadian
      population that unfortunately bears a disproportionate level of illness. One way
      to improve the health of urban Aboriginal youth is to increase their physical
      activity. It is important to understand what this group's beliefs and behaviors
      are on physical activity so that programs that meet their needs can be developed.
      METHODS: This ethnographic study engaged 15 urban Aboriginal youth to understand
      what their physical activity beliefs and behaviors were. RESULTS: Results
      revealed 4 themes: "group physical activity preference," "focus on the family,"
      "traditional physical activity," and "location of residence as a barrier." These
      themes illustrated that urban Aboriginal youth have a preference for group
      physical activity and enjoy traditional Aboriginal forms of activity. Results
      also showed that the family plays a critical role in their physical activity
      patterns. Lastly, participants in this study believed that their location of
      residence was a barrier to physical activity. CONCLUSION: Community leaders need
      to be sensitive to the barriers that this cultural group faces and build on the
      strengths that are present among this group when developing physical activity
      programming.

PMID- 25599516
TI  - Plasmonic core-shell nanoparticles for SERS detection of the pesticide thiram:
      size- and shape-dependent Raman enhancement.
AB  - We systematically investigated the size- and shape-dependent SERS activities of
      plasmonic core-shell nanoparticles towards detection of the pesticide thiram.
      Monodisperse Au@Ag nanocubes (NCs) and Au@Ag nanocuboids (NBs) were synthesized
      and their Ag shell thickness was precisely adjusted from ~1 nm to ~16 nm. All
      these nanoparticles were used as SERS substrates for thiram detection, and the
      Raman intensities with three different lasers (514 nm, 633 nm and 782 nm) were
      recorded and compared. Our results clearly show that: (1) the excitation
      wavelength discriminated particle shapes regardless of particle sizes, and the
      maximized Raman enhancement was observed when the excitation wavelength
      approaches the SERS peak (provided there is significant local electric field
      confinement on the plasmonic nanostructures at that wavelength); (2) at the
      optimized laser wavelength, the maximum Raman enhancement was achieved at a
      certain threshold of particle size (or silver coating thickness). By exciting
      particles at their optimized sizes with the corresponding optimized laser
      wavelengths, we achieved a detection limit of roughly around 100 pM and 80 pM for
      NCs and NBs, respectively. 

PMID- 25599517
TI  - Fog collecting biomimetic surfaces: Influence of microstructure and wettability.
AB  - We analyzed the fog collection efficiency of three different sets of samples:
      replica (with and without microstructures), copper wire (smooth and microgrooved)
      and polyolefin mesh (hydrophilic, superhydrophilic and hydrophobic). The
      collection efficiency of the samples was compared in each set separately to
      investigate the influence of microstructures and/or the wettability of the
      surfaces on fog collection. Based on the controlled experimental conditions
      chosen here large differences in the efficiency were found. We found that
      microstructured plant replica samples collected 2-3 times higher amounts of water
      than that of unstructured (smooth) samples. Copper wire samples showed similar
      results. Moreover, microgrooved wires had a faster dripping of water droplets
      than that of smooth wires. The superhydrophilic mesh tested here was proved more
      efficient than any other mesh samples with different wettability. The amount of
      collected fog by superhydrophilic mesh was about 5 times higher than that of
      hydrophilic (untreated) mesh and was about 2 times higher than that of
      hydrophobic mesh. 

PMID- 25599518
TI  - Comment on "Longitudinal Results of Intratympanic Injection of Budesonide for
      Otitis Media with Effusion in Children Over 12 Years and Adults".

PMID- 25599519
TI  - Spin-crossover behaviors in solvated cobalt(ii) compounds.
AB  - Two solvated cobalt(ii) terpyridine complexes, [Co(MeO-terpy)2](BF4)2.H2O (.H2O)
      and [Co(MeO-terpy)2](BF4)2.acetone (.acetone) were prepared. Annealing each of
      these complexes resulted in the formation of two desolvated species, and ,
      respectively. .H2O and exhibited two-step and gradual SCO. The compound .acetone
      has high-spin at all temperatures and undergoes a reverse spin transition due to
      a phase change. 

PMID- 25599521
TI  - Quantitative depth profiling of Ce(3+) in Pt/CeO2 by in situ high-energy XPS in a
      hydrogen atmosphere.
AB  - The redox property of ceria is a key factor in the catalytic activity of ceria
      based catalysts. The oxidation state of well-defined ceria nanocubes in gas
      environments was analysed in situ by a novel combination of near-ambient pressure
      X-ray Photoelectron Spectroscopy (XPS) and high-energy XPS at a synchrotron X-ray
      source. In situ high-energy XPS is a promising new tool to determine the
      electronic structure of matter under defined conditions. The aim was to
      quantitatively determine the degree of cerium reduction in a nano-structured
      ceria-supported platinum catalyst as a function of the gas environment. To obtain
      a non-destructive depth profile at near-ambient pressure, in situ high-energy XPS
      analysis was performed by varying the kinetic energy of photoelectrons from 1 to
      5 keV, and, thus, the probing depth. In ceria nanocubes doped with platinum,
      oxygen vacancies formed only in the uppermost layers of ceria in an atmosphere of
      1 mbar hydrogen and 403 K. For pristine ceria nanocubes, no change in the cerium
      oxidation state in various hydrogen or oxygen atmospheres was observed as a
      function of probing depth. In the absence of platinum, hydrogen does not
      dissociate and, thus, does not lead to reduction of ceria. 

PMID- 25599522
TI  - Near-field magnetostatics and Neel-Brownian interactions mediated magneto
      rheological characteristics of highly stable nano-ferrocolloids.
AB  - Magnetic nanocolloids consisting of synthesized superparamagnetic iron(II,III)
      oxide nanoparticles (SPION) (5-15 nm) dispersed in poly(ethylene glycol) (PEG)
      and a nano-silica complex have been synthesized. The PEG-nano-silica complex
      physically encapsulates the SPIONs, ensuring that there is no phase separation
      under high magnetic fields (~1.2 T). Exhaustive magneto-rheological
      investigations have been performed to understand the structural behavior and
      response of the ferrocolloids. Remarkable stability and reversibility have been
      observed under magnetic field for concentrated systems. The results show the
      impact of particle concentration, size and encapsulation efficiency on parameters
      such as shear viscosity, yield stress, viscoelastic moduli, magneto-viscous
      hysteresis, and so on. Analytical models to reveal the system mechanism and
      mathematically predict the magneto-viscosity and magneto-yield stress have been
      developed. The mechanistic approach based on near-field magnetostatics and Neel
      Brownian interactivities could predict the colloidal properties under the effect
      of the magnetic field accurately. The colloid exhibits amplified storage and loss
      moduli together with a highly augmented linear viscoelastic region under magnetic
      stimuli. The transition of the colloidal state from the fluidic phase to the soft
      condensed phase and its viscoelastic stimuli under the influence of a magnetic
      field has been explained based on the mathematical analysis. The remarkable
      stability, magnetic properties and accurate physical models reveal promise for
      the colloids in transient situations, namely, magneto
      microelectromechanical/nanoelectromechanical devices, anti-seismic damping,
      biomedical invasive treatments, and so on.

PMID- 25599520
TI  - Association of pituitary adenylate cyclase-activating polypeptide with cognitive
      decline in mild cognitive impairment due to Alzheimer disease.
AB  - IMPORTANCE: There is a deficit of pituitary adenylate cyclase-activating
      polypeptide (PACAP) in patients with neuropathologically confirmed Alzheimer
      dementia. However, whether this deficit is associated with the earlier stages of
      Alzheimer disease (AD) is unknown. This study was conducted to clarify the
      association between PACAP biomarkers and preclinical, mild cognitive impairment
      (MCI), and dementia stages of AD in postmortem brain tissue. OBJECTIVES: To
      examine PACAP and PACAP receptor levels in postmortem brain tissues and
      cerebrospinal fluid from cognitively and neuropathologically normal control
      individuals, patients with MCI due to AD (MCI-AD), and individuals with AD;
      analyze the relationship between PACAP, cognitive, and pathologic features; and
      propose a model to assess these relationships. DESIGN, SETTING, AND PARTICIPANTS:
      We measured PACAP and its receptor (PAC1) levels using enzyme-linked immunoassay.
      A total of 35 cases were included. All the brain tissue and cerebrospinal fluid
      samples were selected from Banner Sun Health Research Institute Brain and Body
      Donation Program. All cognitive test results were in record with the Arizona
      Alzheimer's Consortium. MAIN OUTCOMES AND MEASURES: A comparison of PACAP and
      PAC1 levels among the healthy controls, MCI-AD, and AD dementia groups, as well
      as a systematic correlation analysis between PACAP level, cognitive performance,
      and pathologic severity. RESULTS: The PACAP levels in cerebrospinal fluid, the
      superior frontal gyrus, and the middle temporal gyrus were inversely related to
      dementia severity. The PACAP levels in cerebrospinal fluid correlated with the
      Mattis Dementia Rating Scale score (Pearson r = 0.50; P = .03) and inversely
      correlated with total amyloid plaques (Pearson r = -0.48; P < .01) and tangles
      (Pearson r = -0.55; P = .01) in the brain. The PACAP in the superior frontal
      gyrus and middle temporal gyrus correlated with the Stroop Color-Word
      Interference Test (Pearson r = 0.58; P < .01) and the Auditory Verbal Learning
      Test-Total Learning (Pearson r = 0.33; P = .02), respectively. The PACAP in the
      primary visual cortex did not correlate with the Judgment of Line orientation
      test (P = .14). Furthermore, the PAC1 level in the superior frontal gyrus showed
      an upregulation in MCI-AD but not in AD. The pharmacodynamic model of the PACAP
      PAC1 interaction best predicted cognitive function in the superior frontal gyrus,
      but it was less predictive in the middle temporal gyrus and failed to be
      predictive in the primary visual cortex. CONCLUSIONS AND RELEVANCE: Deficits in
      PACAP are associated with clinical severity in the MCI and dementia stages of AD.
      Additional studies are needed to clarify the role of PACAP deficits in the
      predisposition to, pathogenesis of, and treatment of AD.

PMID- 25599523
TI  - Improving Medication Administration Safety in a Community Hospital Setting Using
      Lean Methodology.
AB  - Virtually all health care organizations have goals of improving patient safety,
      but despite clear goals and considerable investments, gains have been limited.
      This article explores a community hospital's resounding success using Lean
      methodology to improve medication administration safety with process changes
      designed by engaged employees and leaders with the knowledge and skill to effect
      improvements. This article inspires an interdisciplinary approach to quality
      improvement using reproducible strategies. 

PMID- 25599524
TI  - Occupational physical activity and 20-year incidence of acute myocardial
      infarction: results from the Kuopio Ischemic Heart Disease Risk Factor Study.
AB  - OBJECTIVES: This study aimed to assess the effects of physically demanding work -
      measured as energy expenditure (EE) during occupational physical activities (OPA)
      - on risk of acute myocardial infarction (AMI) among men with and without
      preexisting ischemic heart disease (IHD). METHODS: The 20-year prospective study
      examined 1891 middle-aged working men using absolute (kcal/day) and relative
      (relative aerobic strain and percent oxygen uptake reserve) measures of EE.
      Linear and quadratic hazard models were explored in Cox regression analyses
      adjusting for 19 potential confounders and considering interactions with baseline
      IHD. RESULTS: Relative EE measures were positively associated with 20-year
      incidence of AMI in linear and quadratic hazard models and interacted with IHD.
      Each 10% increase of relative aerobic strain increased AMI risk by 18% among men
      without IHD [hazard ratio (HR) 1.18, 95% confidence interval (95% CI) 1.08-1.28,
      P=0.001] and by 8% among men with IHD (HR 1.08, 95% CI 0.98-1.20, P=0.129) in
      fully adjusted linear models. Results for quadratic models and percent oxygen
      uptake reserve were similar. Absolute EE did not predict AMI. Age, baseline IHD,
      systolic blood pressure, anti-hypertensive medication, body mass index, blood
      glucose, low-density lipoprotein cholesterol, cholesterol-lowering medication,
      mental stress, and smoking were independently associated with AMI, but not
      income, social support, alcohol, or conditioning leisure-time physical activity.
      CONCLUSION: In contrast to absolute EE, relative workload measures that take
      individual fitness into account were positively associated with AMI incidence
      among men without IHD. For men with IHD, associations were also positive but
      weaker possibly due to healthy worker selection effects. These findings provide
      evidence for a positive association between OPA and AMI among men.

PMID- 25599525
TI  - Calculating average surface enhancement factors of randomly nanostructured
      electrodes by a combination of SERS and impedance spectroscopy.
AB  - Polyhedron Ag nanostructures were created on top of a polished Au electrode via
      step-wise electrodeposition and tested as substrates for SERS spectroscopy.
      Average Raman enhancement factors were derived by combining SERS measurements
      with electrochemical impedance spectroscopy (EIS), which is able to determine the
      electroactive surface area of a randomly nanostructured surface. Depending on the
      deposition step an alternating increase and decrease of surface area was observed
      while the SERS intensity showed a clear maximum for the first deposition cycle.
      SEM pictures reveal the formation of Ag polyhedrons that are randomly dispersed
      on the Au surface. Furthermore the presence of a sub nanostructure on top of the
      polyhedron after the first deposition cycle is observed which becomes smoother
      after subsequent deposition cycles. Correlating the SEM pictures with SERS and
      EIS measurements it is concluded that the coral-like sub nanostructure is
      dominating the enhancement factor while the polyhedron structure itself only
      plays a minor role for electromagnetic field enhancement. 

PMID- 25599527
TI  - Structural diversity of the microbial surfactin derivatives from selective
      esterification approach.
AB  - Surfactin originated from genus Bacillus is composed of a heptapeptide moiety
      bonded to the carboxyl and hydroxyl groups of a beta-hydroxy fatty acid and it
      can be chemically modified to prepare the derivatives with different structures,
      owing to the existence of two free carboxyl groups in its peptide loop. This
      article presents the chemical modification of surfactin esterified with three
      different alcohols, and nine novel surfactin derivatives have been separated from
      products by the high performance liquid chromatography (HPLC). The novel
      derivatives, identified with Fourier transform infrared spectroscopy (FT-IR) and
      electrospray ionization mass spectrometry (ESI-MS), are the mono-hexyl-surfactin
      C14 ester, mono-hexyl-surfactin C15 ester, mono-2-methoxy-ethyl-surfactin C14
      ester, di-hexyl-surfactin C14 ester, di-hexyl-surfactin ester C15, di-2-methoxy
      ethyl-surfactin ester C14, di-2-methoxy-ethyl-surfactin ester C15, di-6-hydoxyl
      hexyl-surfactin C14 ester and, di-6-hydoxyl-hexyl-surfactin C15 ester. The
      reaction conditions for esterification were optimized and the dependence of
      yields on different alcohols and catalysts were discussed. This study shows that
      esterification is one of the most efficient ways of chemical modification for
      surfactin and it can be used to prepare more derivatives to meet the needs of
      study in biological and interfacial activities. 

PMID- 25599526
TI  - Cued recall of alcohol advertising on television and underage drinking behavior.
AB  - IMPORTANCE: Alcohol is the most common drug among youth and a major contributor
      to morbidity and mortality worldwide. Billions of dollars are spent annually
      marketing alcohol. OBJECTIVE: To examine the reach of television alcohol
      advertising and its effect on drinking among underage youth. DESIGN, SETTING, AND
      PARTICIPANTS: Longitudinal telephone- and web-based surveys conducted in 2011 and
      2013 involving 2541 US adolescents 15 to 23 years of age at baseline, with 1596
      of these adolescents completing the follow-up survey. Cued recall of television
      advertising images for top beer and distilled spirits brands that aired
      nationally in 2010-2011 (n = 351). Images were digitally edited to remove
      branding, and the respondents were queried about 20 randomly selected images. An
      alcohol advertising receptivity score was derived (1 point each for having seen
      the ad and for liking it, and 2 points for correct brand identification). Fast
      food ads that aired nationally in 2010-2011 (n = 535) were similarly queried to
      evaluate message specificity. MAIN OUTCOMES AND MEASURES: Among the underage
      youth at baseline, we determined (1) the onset of drinking among those who never
      drank, (2) the onset of binge drinking among those who were never binge drinkers,
      and (3) the onset of hazardous drinking among those with an Alcohol Use Disorders
      Identification Test consumption subscore of less than 4. Multivariate regressions
      were used to predict each outcome, controlling for covariates (demographics,
      drinking among friends and parents, and sensation seeking), weighting to the US
      population, and using multiple imputation to address loss to follow-up. RESULTS:
      Underage participants were only slightly less likely than participants of legal
      drinking age to have seen alcohol ads (the mean percentage of ads seen were
      23.4%, 22.7%, and 25.6%, respectively, for youth 15-17, 18-20, and 21-23 years of
      age; P < .005). The transition to binge and hazardous drinking occurred for 29%
      and 18% of youth 15 to 17 years of age and for 29% and 19% of youth 18 to 20
      years years of age, respectively. Among underage participants, the alcohol
      advertising receptivity score independently predicted the onset of drinking
      (adjusted odds ratio [AOR], 1.69 [95% CI, 1.17-2.44]), the onset of binge
      drinking (AOR, 1.38 [95% CI, 1.08-1.77]), and the onset of hazardous drinking
      (AOR, 1.49 [95% CI, 1.19-1.86]). Fast-food advertising receptivity was not
      associated with any drinking outcome. CONCLUSIONS AND RELEVANCE: Receptivity to
      television alcohol advertising predicted the transition to multiple drinking
      outcomes. The findings are consistent with the idea that marketing self
      regulation has failed to keep television alcohol advertising from reaching large
      numbers of underage persons and affecting their drinking patterns.

PMID- 25599530
TI  - The role of the kynurenine pathway of tryptophan metabolism in cardiovascular
      disease. An emerging field.
AB  - Coronary heart disease and stroke, the deadliest forms of cardiovascular disease
      (CVD), are mainly caused by atherosclerosis, a chronic inflammatory disease of
      the artery wall driven by maladaptive immune responses in the vessel wall.
      Various risk factors for CVD influence this pathogenic process, including
      diabetes mellitus, hypertension, dyslipidaemia, and obesity. Indoleamine 2,3
      dioxygenase (IDO), an enzyme catalyzing the rate-limiting step in the kynurenine
      pathway of tryptophan degradation, is strongly induced by inflammation in several
      tissues, including the artery wall. An increasing body of evidence indicates that
      IDO promotes immune tolerance, decreases inflammation, and functions as a
      homeostatic mechanism against excessive immune reactions. This review provides an
      overview of the emerging field of the kynurenine pathway of tryptophan
      degradation in CVD, emphasizing the role of IDO-mediated tryptophan metabolism
      and its metabolites in the modulation of 'classical' cardiovascular risk factors,
      such as hypertension, obesity, lipid metabolism, diabetes mellitus, and in the
      development of atherosclerotic CVD.

PMID- 25599529
TI  - Isolation and expression of NAC genes during persimmon fruit postharvest
      astringency removal.
AB  - NAC genes have been characterized in numerous plants, where they are involved in
      responses to biotic and abiotic stress, including low oxygen stress. High
      concentration of CO2 is one of the most effective treatments to remove
      astringency of persimmon fruit owing to the action of the accumulated anoxia
      metabolite acetaldehyde. In model plants, NAC genes have been identified as being
      responsive to low oxygen. However, the possible relationship between NAC
      transcription factors and persimmon astringency removal remains unexplored. In
      the present research, treatment with a high concentration of CO2 (95%)
      effectively removed astringency of "Mopan" persimmon fruit by causing decreases
      in soluble tannin. Acetaldehyde content increased in response to CO2 treatment
      concomitantly with astringency removal. Using RNA-seq and Rapid amplification of
      cDNA ends (RACE), six DkNAC genes were isolated and studied. Transcriptional
      analysis indicated DkNAC genes responded differentially to CO2 treatment; DkNAC1,
      DkNAC3, DkNAC5 and DkNAC6 were transiently up-regulated, DkNAC2 was abundantly
      expressed 3 days after treatment, while the DkNAC4 was suppressed during
      astringency removal. It is proposed that DkNAC1/3/5/6 could be important
      candidates as regulators of persimmon astringency removal and the roles of other
      member are also discussed. 

PMID- 25599528
TI  - Surveillance and cleavage of eukaryotic tRNAs.
AB  - Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many
      other crucial functions. This includes various roles in the regulation of gene
      expression, stress responses, metabolic processes and priming reverse
      transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among the most
      stable molecules. Nevertheless, they are not eternal. As key elements of cell
      function, tRNAs need to be continuously quality-controlled. Two tRNA surveillance
      pathways have been identified. They act on hypo-modified or mis-processed pre
      tRNAs and on mature tRNAs lacking modifications. A short overview of these two
      pathways will be presented here. Furthermore, while the exoribonucleases acting
      in these pathways ultimately lead to complete tRNA degradation, numerous tRNA
      derived fragments (tRFs) are present within a cell. These cleavage products of
      tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs)
      and are suspected to have important regulatory functions. The tRFs are
      evolutionarily widespread and created by cleavage at different positions by
      various endonucleases. Here, we review our present knowledge on the biogenesis
      and function of tRFs in various organisms. 

PMID- 25599531
TI  - The human Bosniak model applied to a cat with renal cystadenoma. A classification
      to differentiate benign and malignant cystic renal masses via computed tomography
      and ultrasound.
AB  - A 13-year-old domestic shorthair cat was presented with weight loss and azotemia.
      Abdominal ultrasound revealed a large cystic space- occupying lesion with
      multiple septae in the left kidney. A core needle biopsy yielded a renal
      cystadenoma originating from the epithelial cells. This report describes the
      clinical, ultrasonographic and computed tomographic features and the growth
      progression of a renal cystadenoma. We describe the first attempt to apply the
      human Bosniak classification to a cat with renal cystic neoplasia to
      differentiate between benign and malignant lesions. Cystadenoma should be a
      differential diagnosis in cases of renal cystic space-occupying lesions. Other
      differentials, imaging features to differentiate benign and malignant lesions and
      the risk of malignant transformation will be discussed. 

PMID- 25599533
TI  - Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine.
AB  - Hexameric ATP-dependent proteases and protein remodeling machines use conserved
      loops that line the axial pore to apply force to substrates during the mechanical
      processes of protein unfolding and translocation. Whether loops from multiple
      subunits act independently or coordinately in these processes is a critical
      aspect of the mechanism but is currently unknown for any AAA+ machine. By
      studying covalently linked hexamers of the Escherichia coli ClpX unfoldase
      bearing different numbers and configurations of wild-type and mutant pore loops,
      we show that loops function synergistically, and the number of wild-type loops
      required for efficient degradation is dependent on the stability of the protein
      substrate. Our results support a mechanism in which a power stroke initiated in
      one subunit of the ClpX hexamer results in the concurrent movement of all six
      pore loops, which coordinately grip and apply force to the substrate. 

PMID- 25599534
TI  - Mapping spatial heterogeneity in the tumor microenvironment: a new era for
      digital pathology.
AB  - The emergent field of digital pathology employing automated image analysis
      techniques is to revolutionize traditional pathology at the center of clinical
      diagnostics. Histological images provide important tumor features unavailable in
      molecular profiling or omics data- the spatial context of tumor and stromal cells
      at single-cell resolution. Methods to map the spatial and morphological patterns
      of cancer and normal cells can contribute to a more comprehensive understanding
      of the highly heterogeneous tumor microenvironment. This review focuses on
      methods that help expand our knowledge of intra-tumoral spatial heterogeneity of
      the tumor microenvironment and their potential synergies with molecular profiling
      technologies. 

PMID- 25599532
TI  - The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine.
AB  - Albicidin is a potent DNA gyrase inhibitor produced by the sugarcane pathogenic
      bacterium Xanthomonas albilineans. Here we report the elucidation of the hitherto
      unknown structure of albicidin, revealing a unique polyaromatic oligopeptide
      mainly composed of p-aminobenzoic acids. In vitro studies provide further
      insights into the biosynthetic machinery of albicidin. These findings will enable
      structural investigations on the inhibition mechanism of albicidin and its
      assessment as a highly effective antibacterial drug. 

PMID- 25599535
TI  - Upregulation of integrin beta4 promotes epithelial-mesenchymal transition and is
      a novel prognostic marker in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and often lethal
      malignant tumor. Several studies have shown that epithelial-mesenchymal
      transition (EMT) is frequently observed in clinical samples of PDA and is related
      to high metastatic rates and poor outcomes. To identify candidate molecules
      regulating EMT in PDA, we previously used cDNA microarray analysis and identified
      integrin beta4 (ITGB4) as one of the genes upregulated in high-EMT xenografts
      derived from PDA patients. The aim of the current study was to clarify the
      clinicopathological and functional significance of ITGB4 overexpression in PDA.
      ITGB4 upregulation in high-EMT xenografts was confirmed by immunohistochemistry.
      Immunohistochemical analyses of 134 surgically resected PDA cases revealed
      intratumoral heterogeneity with respect to ITGB4 expression and showed that
      cancer cells undergoing EMT often display strong diffuse ITGB4 expression. High
      levels of ITGB4 expression were significantly correlated with the hallmarks of
      EMT (solitary cell infiltration, reduced E-cadherin expression, and increased
      vimentin expression), with high tumor grade, and with the presence of lymph node
      metastasis, and showed an independent prognostic effect. Immunocytochemical
      analyses of PDA cell lines revealed that localization of ITGB4 changed from
      regions of cell-cell contact to diffuse cytoplasm and cell edges with occasional
      localization in filopodia during EMT. Knockdown of ITGB4 reduced the migratory
      and invasive ability of PDA cells. Overexpression of ITGB4 promoted cell
      scattering and cell motility in combination with downregulation of E-cadherin and
      upregulation of vimentin expression. In conclusion, we elucidated the prognostic
      and clinicopathological significance of ITGB4 overexpression in PDA and also the
      potential role for ITGB4 in the regulation of cancer invasion and EMT. 

PMID- 25599537
TI  - Therapeutic refractive surgery.

PMID- 25599536
TI  - Novel genotype-phenotype associations in human cancers enabled by advanced
      molecular platforms and computational analysis of whole slide images.
AB  - Technological advances in computing, imaging, and genomics have created new
      opportunities for exploring relationships between histology, molecular events,
      and clinical outcomes using quantitative methods. Slide scanning devices are now
      capable of rapidly producing massive digital image archives that capture
      histological details in high resolution. Commensurate advances in computing and
      image analysis algorithms enable mining of archives to extract descriptions of
      histology, ranging from basic human annotations to automatic and precisely
      quantitative morphometric characterization of hundreds of millions of cells.
      These imaging capabilities represent a new dimension in tissue-based studies, and
      when combined with genomic and clinical endpoints, can be used to explore
      biologic characteristics of the tumor microenvironment and to discover new
      morphologic biomarkers of genetic alterations and patient outcomes. In this
      paper, we review developments in quantitative imaging technology and illustrate
      how image features can be integrated with clinical and genomic data to
      investigate fundamental problems in cancer. Using motivating examples from the
      study of glioblastomas (GBMs), we demonstrate how public data from The Cancer
      Genome Atlas (TCGA) can serve as an open platform to conduct in silico tissue
      based studies that integrate existing data resources. We show how these
      approaches can be used to explore the relation of the tumor microenvironment to
      genomic alterations and gene expression patterns and to define nuclear
      morphometric features that are predictive of genetic alterations and clinical
      outcomes. Challenges, limitations, and emerging opportunities in the area of
      quantitative imaging and integrative analyses are also discussed. 

PMID- 25599538
TI  - Influence of femtosecond lenticule extraction and small incision lenticule
      extraction on corneal nerve density and ocular surface: a 1-year prospective,
      confocal, microscopic study.
AB  - PURPOSE: To compare the influence of femtosecond lenticule extraction (FLEx) and
      small incision lenticule extraction (SMILE) on corneal nerve density and the
      ocular surface for equivalent degrees of correction of myopia. METHODS: Sixty
      eyes of 30 patients (8 males and 22 females, mean age: 31.0 +/- 6.0 years) were
      included in the study. The patients underwent FLEx in 1 eye and SMILE in the
      other eye by random assignment. Subbasal nerve density was measured using
      confocal microscopy preoperatively and at 1 week, 1 and 3 months, and 1 year
      postoperatively. Ocular surface parameters such as Schirmer's test results, tear
      film break-up time, and corneal sensation were performed preoperatively and at 1
      and 3 months postoperatively. RESULTS: In the FLEx group, subbasal nerve density
      was 18,390 +/- 6,090 um/mm(2) preoperatively and 5,770 +/- 3,490 um/mm(2) at 1
      year postoperatively (P < .001, Dunnett's test). In the SMILE group, subbasal
      nerve density was 16,810 +/- 6,220 um/mm(2) preoperatively and 11,870 +/- 8,200
      um/mm(2) at 1 year postoperatively (P = .21). The decrease in corneal nerve
      density was significantly less after SMILE than after FLEx at all postoperative
      visits (Mann-Whitney U test, P < .05). FLEx resulted in a significant decrease in
      Schirmer's test results, tear film break-up time, and corneal sensation at all
      postoperative visits, whereas SMILE induced no significant changes in these
      parameters (P > .05). CONCLUSIONS: There was less damage to the sub-basal nerve
      plexus of the cornea and less effect on the ocular surface parameters after SMILE
      than after FLEx.

PMID- 25599539
TI  - Development of the continuous curvilinear lenticulerrhexis technique for small
      incision lenticule extraction.
AB  - PURPOSE: To develop and evaluate the new continuous curvilinear lenticulerrhexis
      (CCL) technique for small incision lenticule extraction. METHODS: Thirty-one eyes
      of 20 patients with myopia were included in the study. The CCL technique for
      lenticule extraction was developed and used in 16 eyes of 10 patients (CCL
      group). The traditional technique of lenticule extraction was used in 15 eyes of
      10 patients (traditional group). Uncorrected and corrected distance visual
      acuity, manifest refraction, lenticule quality, the duration of the extraction
      procedure, microdistorsions in Bowman's layer under optical coherence tomography
      (Optovue OCT; Optovue, Inc., Fremont, CA), and adverse events were evaluated at 1
      day and 1 month postoperatively. RESULTS: At the first postoperative month, all
      eyes in both groups had an uncorrected distance visual acuity of 1.0 or better.
      The safety indices were 1.12 and 1.09 for the CCL and traditional groups,
      respectively. The efficacy indices were 1.06 and 1.09 for the CCL and traditional
      groups, respectively. All lenticules in the CCL group had intact, round margins,
      whereas one lenticule in the traditional group had a microdefect margin. There
      was no statistically significant difference in duration of lenticule extraction
      or microdistorsions in Bowman's layer. No eyes in the CCL group developed diffuse
      lamellar keratitis, as compared to one eye in the traditional group. CONCLUSIONS:
      The CCL technique exhibited excellent safety and efficacy for myopia correction,
      suggesting CCL is a promising technique that merits further development and
      study.

PMID- 25599540
TI  - Comparison of visual outcomes after variable spot scanning ablation versus
      wavefront-optimized myopic LASIK.
AB  - PURPOSE: To compare the refractive and visual outcomes of variable spot scanning
      ablation versus the wavefront-optimized ablation for myopia and myopic
      astigmatism. METHODS: Fifty patients with myopia who underwent LASIK (100 eyes)
      were divided into two equal groups. Myopic correction performed using the
      variable spot scanning (VSS) ablation with the VISX STAR S4/IR platform (Abbott
      Medical Optics, Inc., Santa Ana, CA) (VSS group) and wavefront-optimized (WFO)
      ablation profile with the WaveLight Allegretto Wave Eye-Q platform (Alcon
      Laboratories, Inc., Fort Worth, TX) (WFO group). Manifest refraction, uncorrected
      distance visual acuity, and corrected distance visual acuity were obtained
      preoperatively and 1 day and 1 and 3 months postoperatively. Wavefront
      measurement and contrast sensitivity testing were done preoperatively and 3
      months postoperatively. RESULTS: Postoperative mean refractive spherical
      equivalent was -0.14 +/- 0.2 diopters for the VSS group and -0.15 +/- 0.28
      diopters for the WFO group. Forty-eight eyes of the VSS group and 47 eyes of the
      WFO group were within +/-0.5 diopters. Postoperative mean corrected distance
      visual acuity was 1.05 +/- 0.13 for the VSS group and 1.06 +/- 0.12 for the WFO
      group. The postoperative uncorrected distance visual acuity was 1.01 +/- 0.16 for
      the VSS group and 1.01 +/- 0.11 for the WFO group. The safety index was 1.12 for
      the VSS group and 1.06 for the WFO group, whereas the efficacy index was 1.07 for
      the VSS group and 1.01 for the WFO group. The mean induced positive spherical
      aberration was 0.041 +/- 0.046 um for the VSS group and 0.195 +/- 0.171 um for
      the WFO group (P < .001). Mesopic contrast sensitivity testing showed no
      statistically significant differences between groups at all tested spatial
      frequencies. CONCLUSIONS: Both VSS and WFO treatments showed similar refractive
      and visual outcomes. Both induced significant positive spherical aberration,
      significantly more with WFO.

PMID- 25599541
TI  - Demarcation line evaluation of iontophoresis-assisted transepithelial corneal
      collagen cross-linking for keratoconus.
AB  - PURPOSE: To evaluate the visualization and depth of the demarcation line with
      anterior segment optical coherence tomography (AS-OCT) after iontophoresis
      assisted transepithelial corneal collagen cross-linking (CXL). METHODS: This
      prospective, consecutive, single center, non-randomized clinical study involved
      15 eyes of 12 patients with keratoconus who underwent an AS-OCT scan (Spectralis;
      Heidelberg Engineering, Inc., Carlsbad, CA) to search for a demarcation line and
      its depth at 1 month after iontophoresis-assisted transepithelial CXL. AS-OCT
      scan measurements were performed by two independent examiners. RESULTS: No
      intraoperative or postoperative complications were observed. Kappa coefficient
      estimation for operator agreement in demarcation line visualization (whether it
      was visualized) was 70.6%. The corneal stromal demarcation line was identified in
      9 eyes (60%) by both examiners. Mean depth of the corneal stromal demarcation
      line was 246.67 +/- 50.72 um (range: 183 to 339 um) for the first examiner and
      241.89 +/- 62.52 um (range: 163 to 358 um) for the second examiner. There were no
      statistically significant differences for the measurements of the paired
      comparisons between the two examiners (P = .61). The Pearson correlation
      coefficient between the measurements was 0.910. CONCLUSIONS: Iontophoresis
      assisted transepithelial CXL creates a demarcation line that can be visualized
      with AS-OCT, which seems less easily distinguishable and shallower than in
      conventional CXL. However, its depth and visualization seems to be more similar
      to conventional CXL than transepithelial CXL.

PMID- 25599542
TI  - Polynomial curve fitting of the corneal profile in 2.2-mm corneal incision
      phacoemulsification.
AB  - PURPOSE: To model incisional axis and perpendicular corneal profile pattern
      changes in 2.2-mm corneal incision phacoemulsification. METHODS: Sixty-seven eyes
      of 67 patients were included in this prospective, interventional, before-after
      paired design study. Power vector components were obtained from keratometry
      (IOLMaster; Carl Zeiss Meditec, Gottingen, Germany) and topography corneal height
      data with the Pentacam HR (Oculus Optikgerate, Wetzlar, Germany) preoperatively
      and at 6 months postoperatively. Second- to sixth-order curve fitting polynomial
      functions of the corneal profile in the incisional and perpendicular axes were
      created using Matlab (The Mathworks, Inc., Natick, MA). Multivariate regression
      analysis was run to study the influence of potential predictors. Correlation of
      changes in corneal elevation and corneal radius with astigmatic parameters was
      also obtained. RESULTS: Significant changes occurred only in the J(0) (P = .004)
      and M (P = .001) parameters. R(2) was high with all of the fitted polynomials
      (0.98 to 0.99) and although the smallest root mean square error was obtained with
      sixth-degree polynomials (0.63 to 1.13), they were more badly conditioned and
      redundant than quadratic polynomials. Corneal flattening changes were obtained on
      axis, which was the most frequent pattern (n = 52, 77%), but were significantly
      larger in the incisional side than the non-incisional side (P = .001) and only
      coupled with perpendicular axis steepening in 23 patients. In the non-incisional
      side on axis, corneal steepening was a relatively frequent pattern (n = 22
      patients, 33%). Predictors studied for profile pattern of change were only near
      significance. Corneal radius of curvature changes were significantly correlated
      with astigmatic parameters. CONCLUSIONS: Polynomial curve fitting is adequate for
      corneal biomechanical modeling of curvature and profile changes in the incisional
      and perpendicular axes of a 2.2-mm incision for phacoemulsification.

PMID- 25599543
TI  - Stromal surface topography-guided custom ablation as a repair tool for corneal
      irregular astigmatism.
AB  - PURPOSE: To illustrate the concept of using a stromal surface topography-guided
      procedure for therapeutic repair after a complication following primary laser
      refractive surgery. METHODS: One case example of therapeutic retreatment for
      short nasal flap after primary LASIK performed in September 2000 is presented.
      The Artemis very high-frequency digital ultrasound arc-scanner (Arc-Scan, Inc.,
      Morrison, CO) was used to obtain layered corneal thickness including epithelial
      thickness profile. Corneal front surface elevation was measured with the Orbscan
      II (Bausch & Lomb, Salt Lake City, UT). Stromal surface height was then
      calculated by subtracting epithelial thickness data from corneal front surface
      elevation data and used to calculate the ablation profile applied to the eye. The
      treatment was performed using the Ultralink system (ArcScan, Inc.), linking the
      ultrasound corneal thickness data with the Technolas 217c laser (Bausch & Lomb).
      Postoperative data were available at 30 days and 13 years. RESULTS: One month
      after treatment, the epithelial thickness map demonstrated that the difference in
      thickness between the thinnest and thickest points located 2.5-mm nasally was
      reduced by 26 um (from 56 to 30 um). The axial difference map demonstrated an
      increase in corneal curvature of approximately 4 diopters where the cornea was
      the flattest nasally, thereby reducing the corneal asymmetry. The anterior
      elevation map also showed a reduced depression nasally. The patient reported
      significant improvement of her night vision. CONCLUSIONS: This case example of
      stromal surface topography-guided treatment demonstrated a significant reduction
      in the irregularity of the stromal surface and an improvement in the topography,
      and the visual quality. Stromal surface topography-guided ablation might become
      the tool of the future for therapeutic repairs because it offers advantages over
      the current alternative of transepithelial phototherapeutic keratectomy.

PMID- 25599546
TI  - Safety of femtosecond laser-assisted cataract surgery performed by surgeons in
      training.

PMID- 25599547
TI  - Immediate effect of ultraviolet-a collagen cross-linking therapy on the
      biomechanics and histology of the human cornea.

PMID- 25599548
TI  - Long-term outcomes after mechanized arcuate keratotomy for the correction of
      astigmatism after keratoplasty.

PMID- 25599549
TI  - Sequence tag-based analysis of microbial population dynamics.
AB  - We describe sequence tag-based analysis of microbial populations (STAMP) for
      characterization of pathogen population dynamics during infection. STAMP analyzes
      the frequency changes of genetically 'barcoded' organisms to quantify population
      bottlenecks and infer the founding population size. Analyses of intraintestinal
      Vibrio cholerae revealed infection-stage and region-specific host barriers to
      infection and showed unexpected V. cholerae migration counter to intestinal flow.
      STAMP provides a robust, widely applicable analytical framework for high
      confidence characterization of in vivo microbial dissemination. 

PMID- 25599552
TI  - Long-term efficacy of allergen specific immunotherapy in atopic dermatitis
      patients in relation to quality of life.
AB  - INTRODUCTION: Atopic dermatitis (AD) is an inflammatory, chronically relapsing
      and highly pruritic skin disorder that considerably effects patients' life.
      Dermatology Life Quality Index (DLQI) is often applied in clinical research in
      order to evaluate the impact of AD on daily performance of patients. AIMS: The
      aim of the study was to evaluate the long-term effect of allergen specific
      immunotherapy (ASIT) on the quality of life in AD patients. MATERIALS AND
      METHODS: 15 patients suffering from AD, allergic to house dust mites or grass
      pollen allergens, who were previously treated with ASIT participated in the
      study. Our treatment with allergy vaccinations was performed during the time
      period between 1995 and 2001. DLQI questionnaires have been filled by the
      patients before the treatment, after termination of ASIT and after 2 - 12 years
      of the observational period. RESULTS: The statistical tests revealed a
      significant difference between the DLQI before ASIT was introduced and after
      termination of ASIT. Every answer except two (describing the influence of skin
      condition on preventing from working or studying and on sexual life) of these
      periods also disclosed statistically significant difference. As for the relation
      between the DLQI after ASIT and the actual one the tests revealed non significant
      difference, also regarding to every single answer of the questionnaire.
      CONCLUSIONS: In relation to improvement of quality of life in AD patients, this
      study confirms the effectiveness of ASIT and it discloses the persistence of its
      results in long-term aspect.

PMID- 25599550
TI  - DIA-Umpire: comprehensive computational framework for data-independent
      acquisition proteomics.
AB  - As a result of recent improvements in mass spectrometry (MS), there is increased
      interest in data-independent acquisition (DIA) strategies in which all peptides
      are systematically fragmented using wide mass-isolation windows ('multiplex
      fragmentation'). DIA-Umpire (http://diaumpire.sourceforge.net/), a comprehensive
      computational workflow and open-source software for DIA data, detects precursor
      and fragment chromatographic features and assembles them into pseudo-tandem MS
      spectra. These spectra can be identified with conventional database-searching and
      protein-inference tools, allowing sensitive, untargeted analysis of DIA data
      without the need for a spectral library. Quantification is done with both
      precursor- and fragment-ion intensities. Furthermore, DIA-Umpire enables targeted
      extraction of quantitative information based on peptides initially identified in
      only a subset of the samples, resulting in more consistent quantification across
      multiple samples. We demonstrated the performance of the method with control
      samples of varying complexity and publicly available glycoproteomics and affinity
      purification-MS data. 

PMID- 25599554
TI  - Hypereosinophilic syndrome due to ETV6/PDGFR-beta gene translocation - a
      diagnostic and therapeutic challenge.
AB  - BACKGROUND: Hypereosinophilic syndromes are characterized by sustained
      overproduction of eosinophils, leading to eosinophilic infiltration, mediator
      release and multi-organ damage. CASE REPORT: A 67 year old male was referred to
      our Department for investigation of a persistent mild-to-moderate eosinophilia,
      identified 10 years previously and unresponsive to corticosteroid treatment. No
      other alterations were present in his differential blood count and physical
      examination was unremarkable. Allergic, rheumatologic and iatrogenic causes of
      eosinophilia were excluded by clinical history, skin-prick tests and blood and
      stool analysis. Iliac crest bone marrow aspiration and biopsy were performed,
      revealing normal cellularity with an increased eosinophil count (6%). RT-PCR of
      the aspirate revealed the presence of transcripts of ETV6/PDGFR-beta t(5;12) gene
      fusion. Karyotype analysis was normal and no mutation in PDFGR-alpha was
      identified. There was no evidence in analytic or imaging studies of cardiac,
      skin, neurologic, pulmonary or splenic involvement. A skin biopsy showed no
      evidence of pathologic infiltration. Initially the patient was treated with a 100
      mg daily dose of imatinib mesylate, a specific inhibitor of the tyrosine-kinase
      domain of PDGFR. Subsequently, the daily dosage was increased to 200 mg/day to
      obtain eosinophil count normalization. Currently, he is under monthly hematologic
      and hepatic function screening. No drug side effects have been reported.
      CONCLUSION: This patient was diagnosed with a rare myeloproliferative variant of
      hypereosinophilic syndrome due to a t(5;12) ETV6/PDGFR-beta translocation.
      Imatinib mesylate, previously used successfully in syndromes associated with
      PDFGR-alpha mutations, showed efficacy in the context of this mutation as well.

PMID- 25599553
TI  - Vaccination during concurrent subcutaneous immunotherapy: safety of simultaneous
      application.
AB  - BACKGROUND: During subcutaneous immunotherapy (SCIT), injections should be
      separated from vaccinations against infectious diseases by at least 1 week,
      because it is assumed that adverse reactions can result from the additional
      activation of the immune system. METARIAL AND METHODS: Data of a total of 875
      individuals receiving SCIT and/or vaccination in one ENT-practice were included
      and analyzed retrospectively. 444 individuals had received vaccination against
      infectious diseases, 336 allergic patients received only SCIT. Moreover, 79
      allergic patients had received vaccination and SCIT injections simultaneously on
      one day in different locations, while 16 patients inadvertently received SCIT
      injections within up to 4 days after vaccination. Some of the patients were
      observed for consecutive years receiving several vaccinations parallel to SCIT.
      Systemic reactions (SRs) during SCIT were classified according to the WAO (World
      Allergy Organization) grading. RESULTS: Patients exclusively receiving
      vaccinations did not report any drug-related SR. One SR third grade and two SRs
      second grade occurred in 3 asthmatic patients exclusively receiving SCIT. The
      patients simultaneously receiving vaccination and SCIT did not have any SR. This
      was also the case for the subjects consecutively receiving parallel SCIT and
      vaccination for up to 5 years. CONCLUSION: The international guidelines for
      allergen-specific immunotherapy (SIT) recommend an intermission of at least one
      week between SCIT and the administration of vaccines. However, these findings
      demonstrate the possibility to shorten or abolish this interval without
      increasing the risk of SRs.

PMID- 25599555
TI  - Grass pollen triggered anaphylaxis in an adolescent boy.
AB  - Anaphylaxis is a rapid onset serious allergic reaction which may be fatal. It is
      usually triggered by an agent such as a food, insect sting, or medication,
      through a mechanism involving immunoglobulin E (IgE) and the high-affinity IgE
      receptor on mast cells or basophils. Anaphylaxis has been rarely described which
      results from pollen antigen exposure. Here, we present unusual anaphylaxis, which
      results from inhaled pollen antigen in a 15-year-old boy. 

PMID- 25599551
TI  - A general method to improve fluorophores for live-cell and single-molecule
      microscopy.
AB  - Specific labeling of biomolecules with bright fluorophores is the keystone of
      fluorescence microscopy. Genetically encoded self-labeling tag proteins can be
      coupled to synthetic dyes inside living cells, resulting in brighter reporters
      than fluorescent proteins. Intracellular labeling using these techniques requires
      cell-permeable fluorescent ligands, however, limiting utility to a small number
      of classic fluorophores. Here we describe a simple structural modification that
      improves the brightness and photostability of dyes while preserving spectral
      properties and cell permeability. Inspired by molecular modeling, we replaced the
      N,N-dimethylamino substituents in tetramethylrhodamine with four-membered
      azetidine rings. This addition of two carbon atoms doubles the quantum efficiency
      and improves the photon yield of the dye in applications ranging from in vitro
      single-molecule measurements to super-resolution imaging. The novel substitution
      is generalizable, yielding a palette of chemical dyes with improved quantum
      efficiencies that spans the UV and visible range. 

PMID- 25599556
TI  - Severe biphasic anaphylaxis to bigarreau cherry in a child.

PMID- 25599557
TI  - Update on systemic nickel allergy syndrome and diet.

PMID- 25599558
TI  - Reply to: Update on systemic nickel allergy syndrome and diet.

PMID- 25599559
TI  - Impact of vitamin D supplementation on adiposity in African-Americans.
AB  - BACKGROUND: African-Americans have higher rates of obesity-associated chronic
      diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with
      obesity status. We investigated whether vitamin D supplementation changes body
      mass index (BMI). SUBJECTS: In total, 328 overweight African-Americans were
      enrolled over three consecutive winter periods (2007-2010) into a randomized,
      double-blind, placebo-controlled trial to receive cholecalciferol supplementation
      (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months.
      Plasma concentrations of 25(OH)D and anthropometric measurements were done at
      baseline, 3 and 6 months. RESULTS: At 3 months, vitamin D supplementation in
      three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any
      significant changes in BMI as compared with placebo group 3-month change in BMI
      per 1000 IU per day estimate (SE): 0.01 (0.039); P=0.78. CONCLUSIONS: In
      overweight African-Americans, short-term high-dose vitamin D supplementation did
      not alter BMI.

PMID- 25599560
TI  - Altered functional connectivity within the central reward network in overweight
      and obese women.
AB  - BACKGROUND/OBJECTIVES: Neuroimaging studies in obese subjects have identified
      abnormal activation of key regions of central reward circuits, including the
      nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to
      examine whether women with elevated body mass index (BMI) show structural and
      resting state (RS) functional connectivity alterations within regions of the
      reward network. SUBJECTS/METHODS: Fifty healthy, premenopausal women, 19
      overweight and obese (high BMI=26-38 kg m(-2)) and 31 lean (BMI=19-25 kg m(-2))
      were selected from the University of California Los Angeles' Oppenheimer Center
      for Neurobiology of Stress database. Structural and RS functional scans were
      collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation
      dynamics of intrinsic brain activity and functional connectivity of the NAcc to
      regions within the reward network were examined. RESULTS: GMV of the left NAcc
      was significantly greater in the high BMI group than in the lean group (P=0.031).
      Altered frequency distributions were observed in women with high BMI compared
      with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and
      in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial
      prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects
      with high BMI had greater connectivity of the left NAcc with bilateral ACC
      (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03)
      in a high frequency band. CONCLUSIONS: Overweight and obese women in the absence
      of food-related stimuli show significant structural and functional alterations
      within regions of reward-related brain networks, which may have a role in altered
      ingestive behaviors.

PMID- 25599563
TI  - Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR , TYMS,
      and TCII genes and the efficacy and toxicity of methotrexate treatment in
      patients with rheumatoid arthritis.
AB  - INTRODUCTION: The differences in drug efficacy and adverse reactions may be
      caused by genetic variations in drug metabolism between individuals. OBJECTIVES:
      The aim of the study was to evaluate the effect of gene polymorphisms on the
      efficacy of therapy and side effects in patients with rheumatoid arthrit s (RA)
      treated with methotrexate (MTX). PATIENTS AND METHODS: A total of 273 Caucasian
      patients with RA were treated with MTX for at least 6 months or stopped MTX
      because of adverse effects. Seven polymorphisms (RFC-1 c.80G>A, GGH c.-401C>T,
      MTHFR c.1298A>C and c.677C>T, TYMS 2R/3R, TYMS 6-bp deletion, and TCII c.593T>C)
      were examined for their effects on MTX efficacy and toxicity. Genomic DNA was
      obtained from peripheral blood leukocytes. RESULTS: Of all patients, 53% reported
      some adverse effects during at least 1 visit, which led to MTX withdrawal in 17%
      of the patients. Adverse effects were more frequent in patients with the MTHFR
      677T allele than in those with the 677CC genotype (odds ratio [OR], 1.97; P =
      0.01) and in those with the GGH 401CC genotype than in those with the GGH 401CT
      and TT genotypes (OR, 3.8; P = 0.05). Furthermore, the MTHFR 677T allele was
      associated with increased activity of aminotransferases (OR, 3.4; P = 0.02). MTX
      related hepatotoxicity and alopecia were more common in patients with the RFC-1
      80AA genotype (OR, 3.5, P = 0.01; OR, 2.4, P = 0.04; respectively). A more rapid
      positive response to MTX therapy was demonstrated in MTHFR 677CC homozygotes (OR,
      3.4; P = 0.001). There were no other associations between single -nucleotide
      polymorphisms and the efficacy of MTX treatment. CONCLUSIONS: The MTHFR 677CC and
      GGH 401TT and CT genotypes were associated with a reduction in the number of MTX
      related adverse events. Future allele and genotype analyses may help identify the
      subsets of RA patients with an increased risk of adverse effects.

PMID- 25599562
TI  - Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses
      in vivo.
AB  - The quality of the adaptive immune response depends on the differentiation of
      distinct CD4(+) helper T cell subsets, and the magnitude of an immune response is
      controlled by CD4(+)Foxp3(+) regulatory T cells (Treg cells). However, how a
      tissue- and cell type-specific suppressor program of Treg cells is
      mechanistically orchestrated has remained largely unexplored. Through the use of
      Treg cell-specific gene targeting, we found that the suppression of allergic
      immune responses in the lungs mediated by T helper type 2 (TH2) cells was
      dependent on the activity of the protein kinase CK2. Genetic ablation of the beta
      subunit of CK2 specifically in Treg cells resulted in the proliferation of a
      hitherto-unexplored ILT3(+) Treg cell subpopulation that was unable to control
      the maturation of IRF4(+)PD-L2(+) dendritic cells required for the development of
      TH2 responses in vivo. 

PMID- 25599564
TI  - Functional normalization of 450k methylation array data improves replication in
      large cancer studies.
AB  - We propose an extension to quantile normalization that removes unwanted technical
      variation using control probes. We adapt our algorithm, functional normalization,
      to the Illumina 450k methylation array and address the open problem of
      normalizing methylation data with global epigenetic changes, such as human
      cancers. Using data sets from The Cancer Genome Atlas and a large case-control
      study, we show that our algorithm outperforms all existing normalization methods
      with respect to replication of results between experiments, and yields robust
      results even in the presence of batch effects. Functional normalization can be
      applied to any microarray platform, provided suitable control probes are
      available. 

PMID- 25599561
TI  - The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and
      maintenance of adipose tissue-resident regulatory T cells.
AB  - Foxp3(+) regulatory T (Treg) cells in visceral adipose tissue (VAT-Treg cells)
      are functionally specialized tissue-resident cells that prevent obesity
      associated inflammation and preserve insulin sensitivity and glucose tolerance.
      Their development depends on the transcription factor PPAR-gamma; however, the
      environmental cues required for their differentiation are unknown. Here we show
      that interleukin 33 (IL-33) signaling through the IL-33 receptor ST2 and myeloid
      differentiation factor MyD88 is essential for development and maintenance of VAT
      Treg cells and sustains their transcriptional signature. Furthermore, the
      transcriptional regulators BATF and IRF4 were necessary for VAT-Treg
      differentiation through direct regulation of ST2 and PPAR-gamma expression. IL-33
      administration induced vigorous population expansion of VAT-Treg cells, which
      tightly correlated with improvements in metabolic parameters in obese mice. Human
      omental adipose tissue Treg cells also showed high ST2 expression, suggesting an
      evolutionarily conserved requirement for IL-33 in VAT-Treg cell homeostasis. 

PMID- 25599567
TI  - Highly tunable interfacial adhesion of glass fiber by hybrid multilayers of
      graphene oxide and aramid nanofiber.
AB  - The performance of fiber-reinforced composites is governed not only by the nature
      of each individual component comprising the composite but also by the interfacial
      properties between the fiber and the matrix. We present a novel layer-by-layer
      (LbL) assembly for the surface modification of a glass fiber to enhance the
      interfacial properties between the glass fiber and the epoxy matrix. Solution
      processable graphene oxide (GO) and an aramid nanofiber (ANF) were employed as
      active components for the LbL assembly onto the glass fiber, owing to their
      abundant functional groups and mechanical properties. We found that the
      interfacial properties of the glass fibers uniformly coated with GO and ANF
      multilayers, such as surface free energy and interfacial shear strength, were
      improved by 23.6% and 39.2%, respectively, compared with those of the bare glass
      fiber. In addition, the interfacial adhesion interactions between the glass fiber
      and the epoxy matrix were highly tunable simply by changing the composition and
      the architecture of layers, taking advantage of the versatility of the LbL
      assembly. 

PMID- 25599565
TI  - Global biogeographic sampling of bacterial secondary metabolism.
AB  - Recent bacterial (meta)genome sequencing efforts suggest the existence of an
      enormous untapped reservoir of natural-product-encoding biosynthetic gene
      clusters in the environment. Here we use the pyro-sequencing of PCR amplicons
      derived from both nonribosomal peptide adenylation domains and polyketide
      ketosynthase domains to compare biosynthetic diversity in soil microbiomes from
      around the globe. We see large differences in domain populations from all except
      the most proximal and biome-similar samples, suggesting that most microbiomes
      will encode largely distinct collections of bacterial secondary metabolites. Our
      data indicate a correlation between two factors, geographic distance and biome
      type, and the biosynthetic diversity found in soil environments. By assigning
      reads to known gene clusters we identify hotspots of biomedically relevant
      biosynthetic diversity. These observations not only provide new insights into the
      natural world, they also provide a road map for guiding future natural products
      discovery efforts. 

PMID- 25599568
TI  - Nanohybrid liposomal cerasomes with good physiological stability and rapid
      temperature responsiveness for high intensity focused ultrasound triggered local
      chemotherapy of cancer.
AB  - The high intensity focused ultrasound (HIFU) and thermosensitive cerasomes
      (HTSCs) were successfully assembled by employing cerasome-forming lipid (CFL) in
      combination with the component lipids of conventional low temperature sensitive
      liposomes (LTSLs) including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC),
      1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)
      2000] (DSPE-PEG-2000) and 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine
      (MSPC). The HTSCs showed spherical shape with a mean diameter around 200 nm,
      exhibiting good biocompatibility. Both hydrophilic and lipophilic drugs can be
      efficiently encapsulated into HTSCs. In addition, the release rate of HTSCs could
      be conveniently adjusted by varying the molar ratios of CFL to DPPC. The drug
      loaded HTSCs showed much longer blood circulation time (half-life >8.50 +/- 1.49
      h) than conventional LTSLs (0.92 +/- 0.17 h). An in vitro study demonstrated that
      the drug loaded HTSCs are highly stable at 37  degrees C and show a burst release
      at 42  degrees C, providing a capability to act synergistically against tumors.
      We found that the HTSCs with a proportion of 43.25% of CFL could release more
      than 90% hydrophilic drugs in 1 min at an elevated temperature of 42  degrees C
      generated by HIFU exposure. After intravenous injection of doxorubicin (DOX)
      loaded HTSCs at 5 mg DOX/kg, followed by double HIFU sonication, the tumor growth
      of the adenocarcinoma (MDA-MB-231) bearing mice could be significantly inhibited.
      Therefore, the drug loaded HTSCs combined with HIFU hold great potential for
      efficient local chemotherapy of cancer due to the ability to deliver high
      concentration of chemotherapy drugs directly to the tumor, achieve maximum
      therapeutic efficacy and minimal side effects, and avoid the damage to the
      healthy tissues caused by systemic administration of drugs. 

PMID- 25599566
TI  - Methylation at the C-2 position of hopanoids increases rigidity in native
      bacterial membranes.
AB  - Sedimentary rocks host a vast reservoir of organic carbon, such as 2-methylhopane
      biomarkers, whose evolutionary significance we poorly understand. Our ability to
      interpret this molecular fossil record is constrained by ignorance of the
      function of their molecular antecedents. To gain insight into the meaning of 2
      methylhopanes, we quantified the dominant (des)methylated hopanoid species in the
      membranes of the model hopanoid-producing bacterium Rhodopseudomonas palustris
      TIE-1. Fluorescence polarization studies of small unilamellar vesicles revealed
      that hopanoid 2-methylation specifically renders native bacterial membranes more
      rigid at concentrations that are relevant in vivo. That hopanoids differentially
      modify native membrane rigidity as a function of their methylation state
      indicates that methylation itself promotes fitness under stress. Moreover,
      knowing the in vivo (2Me)-hopanoid concentration range in different cell
      membranes, and appreciating that (2Me)-hopanoids' biophysical effects are tuned
      by the lipid environment, permits the design of more relevant in vitro
      experiments to study their physiological functions. 

PMID- 25599569
TI  - Impaired dynamic cerebral autoregulation at rest and during isometric exercise in
      type 2 diabetes patients.
AB  - Type 2 diabetes mellitus patients (T2D) have elevated risk of stroke, suggesting
      that cerebrovascular function is impaired. Herein, we examined dynamic cerebral
      autoregulation (CA) at rest and during exercise in T2D patients and determined
      whether underlying systemic oxidative stress is associated with impairments in
      CA. Middle cerebral artery blood velocity and arterial blood pressure (BP) were
      measured at rest and during 2-min bouts of low- and high-intensity isometric
      handgrip performed at 20% and 40% maximum voluntary contraction, respectively, in
      seven normotensive and eight hypertensive T2D patients and eight healthy
      controls. Dynamic CA was estimated using the rate of regulation (RoR). Total
      reactive oxygen species (ROS) and superoxide levels were measured at rest. There
      were no differences in RoR at rest or during exercise between normotensive and
      hypertensive T2D patients. However, when compared with controls, T2D patients
      exhibited lower RoR at rest and during low-intensity handgrip indicating impaired
      dynamic CA. Moreover, the RoR was further reduced by 29 +/- 4% during high
      intensity handgrip in T2D patients (0.307 +/- 0.012/s rest vs. 0.220 +/- 0.014/s
      high intensity; P < 0.01), although well maintained in controls. T2D patients
      demonstrated greater baseline total ROS and superoxide compared with controls,
      both of which were negatively related to RoR during handgrip (e.g., total ROS: r
      = -0.71, P < 0.05; 40% maximum voluntary contraction). Collectively, these data
      demonstrate impaired dynamic CA at rest and during isometric handgrip in T2D
      patients, which may be, in part, related to greater underlying systemic oxidative
      stress. Additionally, dynamic CA is blunted further with high intensity isometric
      contractions potentially placing T2D patients at greater risk for cerebral events
      during such activities.

PMID- 25599570
TI  - Transglutaminase activity is decreased in large arteries from hypertensive rats
      compared with normotensive controls.
AB  - Transglutaminases (TGs) catalyze the formation of covalent cross-links between
      glutamine residues and amine groups. This cross-linking activity has been
      implicated in arterial remodeling. Because hypertension is characterized by
      arterial remodeling, we hypothesized that TG activity, expression, and
      functionality would be increased in the aorta, but not in the vena cava (which
      does not undergo remodeling), from hypertensive rats relative to normotensive
      rats. Spontaneously hypertensive stroke-prone rats (SHRSP) and DOCA-salt rats as
      well as their respective normotensive Wistar-Kyoto or Sprague-Dawley counterparts
      were used. Immunohistochemistry and Western blot analysis measured the presence
      and expression of TG1 and TG2, in situ activity assays quantified active TGs, and
      isometric contractility was used to measure TG functionality. Contrary to our
      hypothesis, the activity (52% DOCA-salt vs. control rats and 56% SHRSP vs.
      control rats, P < 0.05), expression (TG1: 54% DOCA-salt vs. control rats, P >
      0.05, and TG2: 77% DOCA-salt vs. control rats, P < 0.05), and functionality of
      TG1 and TG2 were decreased in the aorta, but not in the vena cava, from
      hypertensive rats. Mass spectrometry identified proteins uniquely amidated by TGs
      in the aorta that play roles in cytoskeletal regulation, redox regulation, and
      DNA/RNA/protein synthesis and regulation and in the vena cava that play roles in
      cytoskeletal regulation, coagulation regulation, and cell metabolism. Consistent
      with the idea that growing cells lose TG2 expression, vascular smooth muscle
      cells placed in culture lost TG2 expression. We conclude that the expression,
      activity, and functionality of TG1 and TG2 are decreased in the aorta, but not in
      the vena cava, from hypertensive rats compared with control rats. 

PMID- 25599573
TI  - Gene transfer of cystathionine beta-synthase into RVLM increases hydrogen sulfide
      mediated suppression of sympathetic outflow via KATP channel in normotensive
      rats.
AB  - Hydrogen sulfide has been shown to have a sympathoinhibitory effect in the
      rostral ventrolateral medulla (RVLM). The present study examined the function of
      cystathionine beta-synthase (CBS)/hydrogen sulfide system in the RVLM, which
      plays a crucial role in the control of blood pressure and sympathetic nerve
      activity. Adenovirus vectors encoding CBS (AdCBS) or enhanced green fluorescent
      protein (AdEGFP) were transfected into the RVLM in normotensive rats. Identical
      microinjection of AdCBS into the RVLM had no effect on systolic blood pressure
      and heart rate (HR) in conscious rats. Acute experiments were performed at day 7
      after gene transfer in anesthetized rats. Microinjection of the CBS inhibitors
      hydroxylamine (HA) or amino-oxyacetate into the RVLM produced an increase in the
      renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and HR.
      There was a potentiation of the increases in RSNA, MAP, and HR because of the CBS
      inhibitors in AdCBS-injected rats compared with AdEGFP-injected rats.
      Pretreatment with pinacidil, a ATP-sensitive potassium (KATP) channel activator,
      abolished the effects of HA in two groups. Microinjection of glibenclamide, a
      KATP channel blocker, produced increases in RSNA, MAP, and HR in AdCBS-injected
      rats. No changes in behavior were observed in AdEGFP-injected rats. Furthermore,
      Western blot analysis indicated an increase in the expression of sulfonylurea
      receptor 2 and inward rectifier K(+) 6.1 in AdCBS-injected rats. These results
      suggest that the increase in KATP channels in the RVLM may be responsible for the
      greater sympathetic outflow and pressor effect of HA in AdCBS-injected rats
      compared with AdEGFP-injected rats. 

PMID- 25599575
TI  - International commercial trade in live carnivores and primates 2006-2012:
      response to Bush et al. 2014.

PMID- 25599572
TI  - Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the
      heart with a primary volume overload.
AB  - Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative
      stress and mitochondrial dysfunction. Because mitochondria are both a source and
      target of ROS, we hypothesized that the mitochondrially targeted antioxidant
      mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in
      VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in
      vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and
      without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical
      stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine
      to measure mitochondrial membrane potential. Transmission electron microscopy and
      immunohistochemistry were used for cardiomyocyte structural assessment. In vitro
      cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial
      ROS production and decreased mitochondrial membrane potential, which were
      significantly improved by MitoQ. ACF had extensive loss of desmin and beta2
      tubulin that was paralleled by mitochondrial disorganization, loss of cristae,
      swelling, and clustering identified by mitochondria complex IV staining and
      transmission electron microscopy. MitoQ improved mitochondrial structural damage
      and attenuated desmin loss/degradation evidenced by immunohistochemistry and
      protein expression. However, LV dilatation and fractional shortening were
      unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not
      affect LV dilatation or function in ACF, these experiments suggest a connection
      of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption
      and mitochondrial damage in the VO of ACF.

PMID- 25599574
TI  - Global conservation status of sponges.
AB  - Sponges are important for maintaining ecosystem function and integrity of marine
      and freshwater benthic communities worldwide. Despite this, there has been no
      assessment of their current global conservation status. We assessed their status,
      accounting for the distribution of research effort; patterns of temporal
      variation in sponge populations and assemblages; the number of sponges on
      threatened species lists; and the impact of environmental pressures. Sponge
      research effort has been variable; marine sponges in the northeastern Atlantic
      and Mediterranean and freshwater sponges in Europe and North America have
      received the most attention. Although sponge abundance has increased in some
      locations since 1990, these were typically on coral reefs, in response to
      declines in other benthic organisms, and restricted to a few species. Few data
      were available on temporal trends in freshwater sponge abundance. Despite over
      8500 described sponge species, only 20 are on threatened species lists, and all
      are marine species from the northeastern Atlantic and Mediterranean. Of the 202
      studies identified, the effects of temperature, suspended sediment, substratum
      loss, and microbial pathogens have been studied the most intensively for marine
      sponges, although responses appear to be variable. There were 20 studies
      examining environmental impacts on freshwater sponges, and most of these were on
      temperature and heavy metal contamination. We found that most sponges do not
      appear to be threatened globally. However, little information is available for
      most species and more data are needed on the impacts of anthropogenic-related
      pressures. This is a critical information gap in understanding sponge
      conservation status.

PMID- 25599571
TI  - Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and
      adult cerebral artery smooth muscle.
AB  - Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters
      cerebral artery contraction-relaxation responses associated with changes in K(+)
      channel activity. We hypothesized that to maintain oxygenation during LTH,
      basilar arteries (BA) in the ovine adult and near-term fetus would show increased
      large-conductance Ca(2+) activated potassium (BK) channel activity. We measured
      BK channel activity, expression, and cell surface distribution by use of patch
      clamp electrophysiology, flow cytometry, and confocal microscopy, respectively,
      in myocytes from normoxic control and LTH adult and near-term fetus BA.
      Electrophysiological data showed that BK channels in LTH myocytes exhibited 1)
      lowered Ca(2+) set points, 2) left-shifted activation voltages, and 3) longer
      dwell times. BK channels in LTH myocytes also appeared to be more
      dephosphorylated. These differences collectively make LTH BK channels more
      sensitive to activation. Studies using flow cytometry showed that the LTH fetus
      exhibited increased BK beta1 subunit surface expression. In addition, in both
      fetal groups confocal microscopy revealed increased BK channel clustering and
      colocalization to myocyte lipid rafts. We conclude that increased BK channel
      activity in LTH BA occurred in association with increased channel affinity for
      Ca(2+) and left-shifted voltage activation. Increased cerebrovascular BK channel
      activity may be a mechanism by which LTH adult and near-term fetal sheep can
      acclimatize to long-term high altitude hypoxia. Our findings suggest that
      increasing BK channel activity in cerebral myocytes may be a therapeutic target
      to ameliorate the adverse effects of high altitude in adults or of intrauterine
      hypoxia in the fetus.

PMID- 25599577
TI  - Age- and procedure-specific differences of epidural analgesia in children--a
      database analysis.
AB  - OBJECTIVE: Several audits demonstrated the safety of epidural catheters in
      children undergoing surgery. Within the present data analysis, we investigated
      whether older compared with younger children and children with specific types of
      surgical procedures might report higher pain scores. METHODS: All children (0-18
      years) treated with an epidural catheter for postoperative pain treatment between
      March 2006 and December 2010 at the University Hospital of Muenster (Germany)
      were included. Postoperative pain intensities, the number of patients with the
      need for additional opioids, and catheter-related complications during placement
      and early postoperative period were analyzed. RESULTS: Data of 830 children
      receiving an epidural catheter (Nthoracic/lumbar = 691; Ncaudal = 139) were
      included. Adolescents (12-18 years) treated with a thoracic/lumbar epidural had
      higher pain scores compared with preschoolers and school children (P < 0.05) and
      received less additional systemic opioids (P < 0.001). In the thoracic/lumbar
      epidural group, children undergoing spine surgery showed comparable pain scores
      with those undergoing thoracic procedures, but had higher pain scores than
      children undergoing abdominal or extremity surgery (P < 0.05). However, children
      undergoing spine surgery received less additional opioids, but this was only
      significant at the first postoperative day (P = 0.032). CONCLUSIONS: This
      database analysis demonstrated that older children and children undergoing
      thoracic or spine surgery reported significant higher pain scores most likely
      because they received less additional opioids. Therefore, a more "aggressive"
      pain treatment (including opioids on demand under appropriate monitoring) might
      further improve postoperative care.

PMID- 25599578
TI  - Further validation of the Motivation for Traumatic Brain Injury Rehabilitation
      Questionnaire (MOT-Q) in patients with acquired brain injury.
AB  - The Motivation for Traumatic Brain Injury Rehabilitation Questionnaire (MOT-Q)
      evaluates motivation for rehabilitation in four subscales: Interest in
      rehabilitation, Lack of anger, Lack of denial, and Reliance on professional help.
      The objective of this study was to further validate the MOT-Q in 122 inpatients
      and 92 outpatients with acquired brain injury (ABI). The main measures were
      motivation for rehabilitation (MOT-Q), self-awareness (Patient Competency Rating
      Scale), and treatment motivation (Visual Analogue Scale). The MOT-Q showed
      adequate feasibility in terms of few items with missing responses and few
      undecided responses. We found no floor or ceiling effects, and significant item
      total MOT-Q correlations for 29 of 31 items. Internal consistency was good for
      the MOT-Q total and acceptable to good for the subscales. The MOT-Q scores were
      significantly intercorrelated except for the subscales Lack of denial and
      Reliance on professional help in the inpatient group. The MOT-Q total and
      subscales were significantly associated with treatment motivation. The Lack of
      denial subscale showed no significant association with treatment motivation and
      no to moderate significant associations with self-awareness. In conclusion, the
      overall MOT-Q is a valid instrument to assess motivation for rehabilitation in
      patients with ABI. Further research is needed to examine the validity of the
      subscales. 

PMID- 25599581
TI  - Perseverative thoughts and subjective health complaints in adolescence: Mediating
      effects of perceived stress and negative affects.
AB  - Stable tendency to perseverative thoughts such as trait rumination and worry can
      influence somatic health. The purpose of the study was to investigate the
      relationship between perseverative thoughts and somatic complaints, and the
      possible mediating effects of perceived stress, negative and positive affectivity
      in adolescence. Having an acute or a chronic condition was also assessed to be
      controlled for and to reveal their effects on symptom reporting. Three hundred
      and six adolescents from 7th to 12th grade with mean age of 16.33 (SD = 1.29)
      participated in the study. Mediation analysis suggested that impact of trait-like
      perseverative thoughts on complaints were mediated by perceived stress and
      negative affectivity. Having an acute condition had also an effect on symptom
      reporting through increased negative affectivity. Our results highlight that
      ruminations or worry as stable intrapersonal characteristics are relevant
      processes in health and can be potential targets in prevention programmes in
      adolescence. 

PMID- 25599580
TI  - Hepatitis B virus infection in hemodialysis patients in Japan: Prevalence,
      incidence and occult hepatitis B virus infection.
AB  - AIM: A survey of hepatitis B virus (HBV) infection in hemodialysis (HD) patients
      was conducted to determine the burden and risk of infection and to suggest
      preventive measures against HBV infection among HD patients at nine hospitals in
      Hiroshima, Japan, from 1999 to 2003. METHODS: HBV markers were investigated for
      1860 HD patients. The prevalence, incidence of HBV and prevalence of occult HBV
      were calculated. RESULTS: The prevalence of hepatitis B surface antigen (HBsAg)
      was 2.6%, the positive rate of anti-hepatitis B core (HBc) was 20.6% and that of
      anti-hepatitis B surface (HBs) was 11.7%. Among 1372 patients who started HD
      after the approval of erythropoietin in Japan in 1991, the prevalence of HBsAg
      was 2.1%. The incidence rate of HBsAg positivity was 0/1000 person-years and the
      incidence of anti-HBc was 0.3/1000 person-years. Among 1812 HBsAg negative
      patients HBV DNA was detected in two: one case was negative for anti-HBc and anti
      HBs, and the other was only positive for anti-HBc. Prevalence of occult HBV was
      0.11%. CONCLUSION: The incidence rate of HBV was much lower than that of
      hepatitis C virus (HCV) in the same cohort. We supposed that the discrepancy
      between incidence rate of HBV and that of HCV was caused by the difference of
      their carrier rates and of their characteristics for persistent infection. So, we
      concluded that it is prerequisite to grasp the burden of HBV carriers in the
      group to prevent new HBV infections in HD patients.

PMID- 25599582
TI  - Distinguishing hyperhidrosis and normal physiological sweat production: new data
      and review of hyperhidrosis data for 1980-2013.
AB  - BACKGROUND: Hyperhidrosis is a condition in which the production of sweat is
      abnormally increased. No objective criteria for the diagnosis of hyperhidrosis
      exist, mainly because reference intervals for normal physiological sweat
      production at rest are unknown. OBJECTIVE: The main objective of this study was
      to establish reference intervals for normal physiological axillary and palmar
      sweat production. METHODS: Gravimetric testing was performed in 75 healthy
      control subjects. Subsequently, these results were compared with findings in a
      cohort of patients with hyperhidrosis and with the results derived from a review
      of data on hyperhidrosis published between 1980 and 2013. RESULTS: Approximately
      90% of the controls had axillary and palmar sweat production rates of below 100
      mg/5 min. In all except one of the axillary and palmar hyperhidrosis studies
      reviewed, average sweat production exceeded 100 mg/5 min. CONCLUSIONS: A sweat
      production rate of 100 mg/5 min as measured by gravimetric testing may be a
      reasonable cut-off value for distinguishing axillary and palmar hyperhidrosis
      from normal physiological sweat production.

PMID- 25599579
TI  - Myocardial conditioning techniques in off-pump coronary artery bypass grafting.
AB  - Off-pump coronary artery bypass surgery by avoiding cardioplegic arrest seems to
      reduce the risk of ischemic myocardial injury. However, even short-term regional
      ischemic periods, hemodynamic instability and arrhythmias associated with the
      procedure can be responsible for myocardial damage. Conditioning, a potential
      cardio-protective tool during on-pump cardiac surgery, has hardly been
      investigated in the context of off-pump surgery. There are virtually no large
      trials on remote ischemic preconditioning and the majority of reports have
      focused on central ischemic conditioning. Similarly, volatile anesthetic agents
      with conditioning effect like ischemic preconditioning have been shown to reduce
      cardiac injury during on-pump procedures but have not been validated in the off
      pump scenario. Here, we review the available evidence on myocardial conditioning,
      either with ischemia/reperfusion or volatile anesthetic agents in patients
      undergoing off-pump coronary artery surgery. 

PMID- 25599583
TI  - Electrocardiographic features of disease progression in arrhythmogenic right
      ventricular cardiomyopathy/dysplasia.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is
      considered a progressive cardiomyopathy. However, data on the clinical features
      of disease progression are limited. The aim of this study was to assess 12-lead
      surface electrocardiographic (ECG) changes during long-term follow-up, and to
      compare these findings with echocardiographic data in our large cohort of
      patients with ARVC/D. METHODS: Baseline and follow-up ECGs of 111 patients from
      three tertiary care centers in Switzerland were systematically analyzed with
      digital calipers by two blinded observers, and correlated with findings from
      transthoracic echocardiography. RESULTS: The median follow-up was 4 years (IQR
      1.9-9.2 years). ECG progression was significant for epsilon waves (baseline 14%
      vs. follow-up 31%, p = 0.01) and QRS duration (111 ms vs. 114 ms, p = 0.04). Six
      patients with repolarization abnormalities according to the 2010 Task Force
      Criteria at baseline did not display these criteria at follow-up, whereas in all
      patients with epsilon waves at baseline these depolarization abnormalities also
      remained at follow-up. T wave inversions in inferior leads were common (36% of
      patients at baseline), and were significantly associated with major
      repolarization abnormalities (p = 0.02), extensive echocardiographic right
      ventricular involvement (p = 0.04), T wave inversions in lateral precordial leads
      (p = 0.05), and definite ARVC/D (p = 0.05). CONCLUSIONS: Our data supports the
      concept that ARVC/D is generally progressive, which can be detected by 12-lead
      surface ECG. Repolarization abnormalities may disappear during the course of the
      disease. Furthermore, the presence of T wave inversions in inferior leads is
      common in ARVC/D.

PMID- 25599584
TI  - Toxoplasma secretory granules: one population or more?
AB  - In Toxoplasma gondii, dense granules are known as the storage secretory
      organelles of the so-called GRA proteins (for dense granule proteins), which are
      destined to the parasitophorous vacuole (PV) and the PV-derived cyst wall.
      Recently, newly annotated GRA proteins targeted to the host cell nucleus have
      enlarged this view. Here we provide an update on the latest developments on the
      Toxoplasma secreted proteins, which to date have been mainly studied at both the
      tachyzoite and bradyzoite stages, and we point out that recent discoveries could
      open the issue of a possible, yet uncharacterized, distinct secretory pathway in
      Toxoplasma. 

PMID- 25599585
TI  - Know your foe: lessons from the analysis of tsetse fly behaviour.
AB  - The emergence of new vector-borne diseases requires new methods of vector
      control. These diseases are often zoonoses associated with wilderness areas, and
      established methods of vector control used in domestic settings (e.g., indoor
      residual spraying, insecticide-treated bednets) are therefore inappropriate.
      Similar difficulties are also emerging with the control of 'old' vector-borne
      diseases such as malaria. Understanding the host-finding behaviour of vectors
      assists the development and application of control methods and aids the
      understanding of epidemiology. Some general lessons are illustrated by reference
      to a century of research on the host-finding behaviour of tsetse flies which
      transmit trypanosomes causing human and animal trypanosomiases, including
      Rhodesian sleeping sickness, a zoonosis associated with wilderness areas of sub
      Saharan Africa. 

PMID- 25599586
TI  - Evolving the world's most dangerous animal.
AB  - The devastating consequences of malaria are well known but many mysteries remain
      about its key protagonists, a handful of Anopheles species. New work provides a
      framework for solving such puzzles, by generation and analysis of whole genome
      assemblies for 16 Anopheles species, with genomic flexibility a key emergent
      theme. 

PMID- 25599587
TI  - Forum on parasite vaccines: a tribute to Declan McKeever.
AB  - Professor Declan McKeever, a much-loved colleague and friend who died in January
      2014, devoted much of his professional life to developing vaccines against tick
      borne diseases of cattle. A conference was held at Hatfield House on the 21st
      October, 2014, bringing together colleagues from across the world to discuss the
      challenges of parasite control and to celebrate Declan's contributions and
      achievements. 

PMID- 25599588
TI  - Solution-processed highly conductive PEDOT:PSS/AgNW/GO transparent film for
      efficient organic-Si hybrid solar cells.
AB  - Hybrid solar cells based on n-Si/poly(3,4-ethylenedioxythiophene):poly(styrene-
      sulfonate) (PEDOT:PSS) heterojunction promise to be a low cost photovoltaic
      technology by using simple device structure and easy fabrication process.
      However, due to the low conductivity of PEDOT:PSS, a metal grid deposited by
      vacuum evaporation method is still required to enhance the charge collection
      efficiency, which complicates the device fabrication process. Here, a solution
      processed graphene oxide (GO)-welded silver nanowires (AgNWs) transparent
      conductive electrode (TCE) was employed to replace the vacuum deposited metal
      grid. A unique "sandwich" structure was developed by embedding an AgNW network
      between PEDOT:PSS and GO with a figure-of-merit of 8.6*10(-3) Omega(-1), which
      was even higher than that of sputtered indium tin oxide electrode (6.6*10(-3)
      Omega(-1)). A champion power conversion efficiency of 13.3% was achieved, because
      of the decreased series resistance of the TCEs as well as the enhanced built-in
      potential (Vbi) in the hybrid solar cells. The TCEs were obtained by facile low
      temperature solution process method, which was compatible with cost-effective
      mass production technology.

PMID- 25599589
TI  - Human mesenchymal stromal cell therapy for prevention and recovery of
      chemo/radiotherapy adverse reactions.
AB  - Cancer treatment plans mainly include chemotherapy, radiotherapy and surgery,
      which exert serious adverse reactions immediately or during the long term after
      cancer therapy in many patients. In several cases, treatment-related adverse
      effects outweigh treatment benefits and worsen the patient's condition. This
      problem is not avoidable with current cancer therapy procedures; therefore,
      improved understanding and earlier prevention and reversion of treatment-related
      complications are particularly important before the lesions become progressive
      and irreversible. Mesenchymal stromal cell therapy is very promising in recent
      clinical research and investigations. Their potential properties such as
      regenerative and reparative functions and anti-inflammatory activity make them
      proper candidates for cell therapy to recover cancer patients from treatment
      related adverse effects or may even prevent them. This article discuss benefits
      of applying human mesenchymal stromal cell therapy after current cancer treatment
      plans, with the purpose of prevention and healing of adverse reactions, faster
      patient recovery after radio/chemotherapy, reducing rates of treatment failure
      and cancer recurrence and increasing patient quality of life after treatment
      cessation. 

PMID- 25599591
TI  - Alpha-fetoprotein is present in the fetal fluids and is increased in plasma of
      mares with experimentally induced ascending placentitis.
AB  - The objectives of this study were to: (i) determine alpha-fetoprotein (AFP)
      concentrations in fetal fluids (FF), and (ii) compare plasma concentrations of
      AFP in mares with placentitis (n=17) and gestationally age-matched control mares
      (n=17). Fetal fluid sampling (FFS, n=7/group) was performed at 0, 5 and 12 days
      post inoculation (DPI) or until abortion. Plasma was harvested daily for 12 days
      or until abortion. Placentitis was induced via intracervical inoculation of
      Streptococcus equi ssp. zooepidemicus. Proteins present in the FF were resolved
      by 1D-SDS-PAGE, and immunoblotting was used to detect the presence of AFP in
      fetal fluids. Concentrations of AFP in FF and plasma were determined with a
      chemiluminescence immunoassay. Mixed models for DPI, and for days from abortion
      (DFA) were used to analyze plasma concentrations of AFP. A protein band ~68kDa
      consistent with the AFP size was present in all samples of fetal fluids examined.
      Immunoblotting for AFP revealed a single protein band (~68kDa) in all samples.
      Concentrations of AFP in FF appeared higher than those in maternal plasma. There
      were effects of time (DPI p<0.0001; DFA p=0.0002) and time-by-group interactions
      (DPI*Group p<0.06; Group*DFA p<0.001). This study confirmed that AFP is present
      in the FF of mares during the third trimester of pregnancy. Experimentally
      induced placentitis was associated with an elevation in maternal plasma
      concentrations of AFP. 

PMID- 25599593
TI  - Editor's Choice - Ten-year Experience with Endovascular Repair of
      Thoracoabdominal Aortic Aneurysms: Results from 166 Consecutive Patients.
AB  - OBJECTIVE: To present a 10 year experience with endovascular thoracoabdominal
      aortic aneurysm (TAAA) repair using fenestrated and branched stent grafts.
      MATERIALS AND METHODS: Consecutive patients with TAAA treated with fenestrated
      and branched stent grafts within the period January 2004-December 2013. Data were
      collected prospectively. RESULTS: 166 patients (125 male, 41 female, mean age
      68.8 +/- 7.6 years) were treated. The mean TAAA diameter was 71 +/- 9.3 mm. Types
      of TAAA were: type I, n = 12 (7.2%), type II, n = 50 (30.1%), type III, n = 53
      (31.9%), type IV, n = 41 (24.8%), and type V, n = 10 (6%). Fifteen (9%) patients
      had an acute TAAA (11 contained rupture, 4 symptomatic). One hundred and eight
      (65%) patients were refused for open surgery earlier. Seventy eight (47%)
      patients had previously undergone one or more open/endovascular aortic
      procedures. Technical success was 95% (157/166). Thirty day operative mortality
      was 7.8% (13/166), with an in hospital mortality of 9% (15/166). Peri-operative
      spinal cord ischemia (SCI) was observed in 15 patients (9%), including permanent
      paraplegia in two (1.2%). Mean follow up was 29.2 +/- 21 months. During follow up
      40 patients died, two of them probably from aneurysm related cause. Re
      intervention, mostly by endovascular means, was needed in 40 (24%) patients.
      Estimated survival at 1, 2, and 5 years was 83% +/- 3%, 78% +/- 3.5%, and 66.6%
      +/- 6.1%, respectively. Estimated target vessel stent patency at 1, 2, and 5
      years was 98% +/- 0.6%, 97% +/- 0.8%, and 94.2% +/- 1.5%, respectively. Estimated
      freedom from re-intervention at 1 and 3 years was 88.3% +/- 2.7%, and 78.4% +/-
      4.5%, respectively. CONCLUSIONS: Endovascular repair of TAAA with fenestrated and
      branched stent grafts in high volume centers appears safe and effective in the
      mid-term in a high risk patient cohort. A considerable reintervention rate should
      be acknowledged, however.

PMID- 25599594
TI  - A safe, simple technique for transseptal catheterization.
AB  - Transseptal catheterization is required for atrial fibrillation ablation and many
      ablations for atrial tachycardias, left atrial flutters, and accessory pathways.
      Using a Brockenbrough needle or other specialized device adds time, expense, and
      risk of potential complications such as atrial or aortic perforation, pericardial
      effusion, and tamponade to these procedures. We present a simple, low-risk
      technique for transseptal catheterization. 

PMID- 25599592
TI  - Sequence and regulation of the porcine FSHR gene promoter.
AB  - Follicle-stimulating hormone (FSH) plays a crucial role in animal reproduction
      and exerts its physiological functions by interacting with the FSH receptor
      (FSHR). The FSHR is exclusively expressed in granulose cells in the ovary and its
      expression level is closely related to granulose cell differentiation and
      follicle maturation. In mammal, most of the follicles undergo atresia, while
      follicle atresia is mainly caused by granulosa cell apoptosis. However, knowledge
      on the transcriptional regulatory mechanisms of the porcine FSHR gene in
      granulosa cell is still limited. In this study, approximately 2.1kb of the
      proximal promoter sequence of the porcine FSHR gene were obtained by genome
      walking, and the regulatory elements and transcription factors in the porcine
      FSHR promoter sequence were predicted. Furthermore, the core promoter region (
      1195/-598) of the porcine FSHR gene was identified using a luciferase assay.
      Subsequently, the relationship between expression levels of the porcine FSHR gene
      and histone H3K9 acetylation levels around the core promoter region (-787/-572)
      in vivo and invitro were analyzed. Our results showed that an increased FSHR gene
      expression level was accompanied with an increase in histone H3K9 acetylation
      levels, suggesting that histone H3K9 acetylation could regulate the expression of
      the porcine FSHR gene. 

PMID- 25599590
TI  - Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus
      infection.
AB  - Variation in the presentation of hereditary immunodeficiencies may be explained
      by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1)
      present with amylopectinosis-associated myopathy with or without hyper
      inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient
      mice exhibit amylopectin-like deposits in the myocardium but show minimal signs
      of hyper-inflammation. However, they show immunodeficiency upon acute infection
      with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium.
      Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic
      cells and macrophages in production of protective cytokines. In contrast, HOIL-1
      deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or
      murine gamma-herpesvirus 68 (MHV68), and these infections conferred a hyper
      inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented
      the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11
      deficient mice following Listeria infection. Thus chronic herpesvirus infection
      generates signs of auto-inflammation and complements genetic immunodeficiency in
      mutant mice, highlighting the importance of accounting for the virome in genotype
      phenotype studies. 

PMID- 25599595
TI  - Implementation of Brazil's "family health strategy": factors associated with
      community health workers', nurses', and physicians' delivery of drug use
      services.
AB  - BACKGROUND: Brazil's "family health strategy" (ESF), provides primary care,
      mostly to individuals in impoverished communities through teams of physicians,
      nurses, and community health workers (CHWs). ESF workers are called upon to offer
      drug use services (e.g., referrals, counseling) as drug use represents an urgent
      public health crisis. New federal initiatives are being implemented to build
      capacity in this workforce to deliver drug use services, yet little is known
      about whether ESF workers are providing drug use services already. Guided by
      social cognitive theory, this study examines factors associated with ESF workers'
      provision of drug use services. METHODS: Cross-sectional surveys were collected
      from 262 ESF workers (168 CHWs, 62 nurses, and 32 physicians) in Mesquita, Rio de
      Janeiro State and Santa Luzia, Minas Gerais State. OUTCOME VARIABLE: provision of
      drug-use services. PREDICTORS: capacity to engage in evidence-based practice
      (EBP), resource constraints, peer support, knowledge of EBP, and job title.
      Logistic regression was used to determine relative influence of each predictor
      upon the outcome. RESULTS: Thirty-nine percent reported providing drug use
      services. Younger workers, CHWs, workers with knowledge about EBP and workers
      that report peer support were more likely to offer drug use services. Workers
      that reported resource constraints and more capacity to implement EBP were less
      likely to offer drug use services. CONCLUSION: ESF workers require education in
      locating, assessing and evaluating the latest research. Mentorship from
      physicians and peer support through team meetings may enhance workers' delivery
      of drug use services, across professional disciplines. Educational initiatives
      aimed at ESF teams should consider these factors as potentially enhancing
      implementation of drug use services. Building ESF workers' capacity to
      collaborate across disciplines and to gain access to tools for providing
      assessment and treatment of drug use issues may improve uptake of new
      initiatives.

PMID- 25599596
TI  - Assessing the harms of cannabis cultivation in Belgium.
AB  - BACKGROUND: Since the 1990s, a shift from the importation of foreign cannabis to
      domestic cultivation has taken place in Belgium, as it has in many other
      countries. This shift has prompted Belgian policy-making bodies to prioritize the
      repression of cannabis cultivation. Against this background, the article aims to
      systematically map and assess for the first time ever the harms associated with
      cannabis cultivation, covering the whole spectrum of growers. METHODS: This study
      is based on a web survey primarily targeting small-scale growers (N=1293) and on
      three interconnected sets of qualitative data on large-scale growers and
      traffickers (34 closed criminal proceedings, interviews with 32 criminal justice
      experts, and with 17 large-scale cannabis growers and three traffickers). The
      study relied on Greenfield and Paoli's (2013) harm assessment framework to
      identify the harms associated with cannabis cultivation and to assess the
      incidence, severity and causes of such harms. RESULTS: Cannabis cultivation has
      become endemic in Belgium. Despite that, it generates, for Belgium, limited harms
      of medium-low or medium priority. Large-scale growers tend to produce more harms
      than the small-scale ones. Virtually all the harms associated with cannabis
      cultivation are the result of the current criminalizing policies. CONCLUSIONS:
      Given the spread of cannabis cultivation and Belgium's position in Europe,
      reducing the supply of cannabis does not appear to be a realistic policy
      objective. Given the limited harms generated, there is scarce scientific
      justification to prioritize cannabis cultivation in Belgian law enforcement
      strategies. As most harms are generated by large-scale growers, it is this
      category of cultivator, if any, which should be the focus of law enforcement
      repression. Given the policy origin of most harms, policy-makers should seek to
      develop policies likely to reduce such harms. At the same time, further research
      is needed to comparatively assess the harms associated with cannabis cultivation
      (and trafficking) with those arising from use.

PMID- 25599597
TI  - Relationships between postnatal plasma oxytocin concentrations and social
      behaviors in cattle.
AB  - We examined the associations between natural individual variations in basal
      oxytocin (OXT) in postnatal cattle and social behavioral traits. At 1, 2 and 6
      weeks of age, the basal OXT exhibited individual variability in 20 Holstein
      heifer calves. Cluster analysis of mean OXT for these time periods obtained two
      subgroups: high OXT (HOXT; n = 9) and low OXT (LOXT; n = 11). Social behaviors
      were observed for 2 days at week 6 after introduction into a four-peer group, and
      at 10-14 months of age (10 months) immediately and 1 week, 1 month and 5 months
      after introduction into 11-15 heifers. At week 6, the main effect of the OXT
      groups was not significant for all social behaviors. At 10 months, there tended
      to be interactions between the OXT groups and time periods with respect to the
      frequency of escape behaviors. LOXT heifers exhibited more escape behaviors than
      HOXT heifers on the first day of the second sociality tests. At 10 months, HOXT
      heifers exhibited both attacking and affiliative behavior for peers more than
      LOXT heifers during 5 months after the second social introduction. This suggests
      that postnatal OXT concentrations may have long-lasting effects on individual
      differences among social behavioral traits in cattle. 

PMID- 25599598
TI  - Keratins in health and disease.
AB  - The cytoprotective keratins (K) compose the intermediate filaments of epithelial
      cells and their inherited and spontaneous mutations give rise to keratinopathies.
      For example, mutations in K1/K5/K10/K14 cause epidermal skin diseases whereas
      simple epithelial K8/K18/K19 variants predispose to development of several liver
      disorders. Due to their abundance, tissue- and context-specific expression,
      keratins constitute excellent diagnostic markers of both neoplastic and non
      neoplastic diseases. During injury and in disease, keratin expression levels,
      cellular localization or posttranslational modifications are altered.
      Accumulating evidence suggests that these changes modulate multiple processes
      including cell migration, tumor growth/metastasis and development of infections.
      Therefore, our understanding of keratins is shifting from diagnostic markers to
      active disease modifiers. 

PMID- 25599600
TI  - Aggregation and the estimated effects of economic conditions on health.
AB  - This paper considers the relationship between economic conditions and health with
      a focus on different approaches to geographic aggregation. After reviewing the
      tradeoffs associated with more- and less-disaggregated analyses, I update earlier
      state-level analyses of mortality and infant health and then consider how the
      estimated effects vary when the analysis is conducted at differing levels of
      geographic aggregation. This analysis reveals that the results are sensitive to
      the level of geographic aggregation with more-disaggregated analyses-particularly
      county-level analyses-routinely producing estimates that are smaller in
      magnitude. Further analyses suggest this is due to spillover effects of economic
      conditions on health outcomes across counties. 

PMID- 25599599
TI  - Prediction of signaling cross-talks contributing to acquired drug resistance in
      breast cancer cells by Bayesian statistical modeling.
AB  - BACKGROUND: Initial success of inhibitors targeting oncogenes is often followed
      by tumor relapse due to acquired resistance. In addition to mutations in targeted
      oncogenes, signaling cross-talks among pathways play a vital role in such drug
      inefficacy. These include activation of compensatory pathways and altered
      activities of key effectors in other cell survival and growth-associated
      pathways. RESULTS: We propose a computational framework using Bayesian modeling
      to systematically characterize potential cross-talks among breast cancer
      signaling pathways. We employed a fully Bayesian approach known as the p 1-model
      to infer posterior probabilities of gene-pairs in networks derived from the gene
      expression datasets of ErbB2-positive breast cancer cell-lines (parental,
      lapatinib-sensitive cell-line SKBR3 and the lapatinib-resistant cell-line SKBR3
      R, derived from SKBR3). Using this computational framework, we searched for cross
      talks between EGFR/ErbB and other signaling pathways from Reactome, KEGG and
      WikiPathway databases that contribute to lapatinib resistance. We identified 104,
      188 and 299 gene-pairs as putative drug-resistant cross-talks, respectively, each
      comprised of a gene in the EGFR/ErbB signaling pathway and a gene from another
      signaling pathway, that appear to be interacting in resistant cells but not in
      parental cells. In 168 of these (distinct) gene-pairs, both of the interacting
      partners are up-regulated in resistant conditions relative to parental
      conditions. These gene-pairs are prime candidates for novel cross-talks
      contributing to lapatinib resistance. They associate EGFR/ErbB signaling with six
      other signaling pathways: Notch, Wnt, GPCR, hedgehog, insulin receptor/IGF1R and
      TGF- beta receptor signaling. We conducted a literature survey to validate these
      cross-talks, and found evidence supporting a role for many of them in
      contributing to drug resistance. We also analyzed an independent study of
      lapatinib resistance in the BT474 breast cancer cell-line and found the same
      signaling pathways making cross-talks with the EGFR/ErbB signaling pathway as in
      the primary dataset. CONCLUSIONS: Our results indicate that the activation of
      compensatory pathways can potentially cause up-regulation of EGFR/ErbB pathway
      genes (counteracting the inhibiting effect of lapatinib) via signaling cross
      talk. Thus, the up-regulated members of these compensatory pathways along with
      the members of the EGFR/ErbB signaling pathway are interesting as potential
      targets for designing novel anti-cancer therapeutics.

PMID- 25599601
TI  - Generation of monoclonal antibodies reactive against subtype specific conserved B
      cell epitopes on haemagglutinin protein of influenza virus H5N1.
AB  - H5-specific monoclonal antibodies may serve as valuable tools for rapid diagnosis
      of H5N1 avian influenza virus. Therefore, conserved H5-specific sequences of the
      haemagglutinin (HA) protein were expressed in Pichia pastoris and used for
      generation of monoclonal antibodies (mAbs). The two mAbs, FD6 and HE4, were
      strongly reactive against native HA protein and exhibited specificity for subtype
      H5. By epitope mapping linear epitopes of mAbs were identified that are highly
      conserved among influenza A virus of subtype H5. Additionally no sequence
      similarities to homologous regions on HA proteins of other influenza A virus
      subtypes (i.e. H1, H3, H7, H9) were detected by sequence alignment analysis. Both
      mAbs did not cross react with native or denatured HA proteins of other influenza
      A virus subtypes. Furthermore, using ELISA and immunofluorescence test mAb FD6
      reacted only to the native H5 protein of recently circulating highly pathogenic
      H5N1 influenza viruses but not to low pathogenic H5N1 isolates. In conclusion,
      the use of the two mAbs in non-molecular tests like antigen-capture-ELISA appears
      promising for detecting influenza A H5N1 virus. 

PMID- 25599602
TI  - Negative effect of heat shock on feline calicivirus release from infected cells
      is associated with the control of apoptosis.
AB  - FCV infection causes rapid cytopathic effects, and its replication results in the
      induction of apoptosis changes in cultured cells. It is well established that the
      survival of apoptotic cells can be enhanced by the expression of heat-shock
      proteins (Hsp) to prevent damage or facilitate recovery. Hsps can act as
      molecular chaperones, but they can also have anti-apoptotic roles by binding to
      apoptotic proteins and inhibiting the activation of caspases, the primary
      mediators of apoptosis. Because apoptosis occurs during FCV infection and heat
      shock (HS) treatment has a cytoprotective role due to the expression of Hsps, we
      studied the effect of the HS response to hyperthermia during FCV infection in
      cultured cells. We found that FCV infection does not inhibit the expression of
      Hsp70 induced by HS and that non-structural and structural protein synthesis was
      not modified during HS treatment. However, HS caused a delay in the appearance of
      a cytopathic effect in infected cells, as well as a reduction in the
      extracellular but not in the cell-associated viral yield. This antiviral effect
      of HS correlates with the inhibition of caspase-3 activation. Thus, the HS
      induced reduction in virus production appeared to be associated with the control
      of apoptosis, supporting previous data that indicate that apoptosis is necessary
      for FCV release. 

PMID- 25599603
TI  - H5N1 influenza virus-like particle vaccine protects mice from heterologous virus
      challenge better than whole inactivated virus.
AB  - The highly pathogenic avian influenza (HPAI) H5N1 virus has become highly
      enzootic since 2003 and has dynamically evolved to undergo substantial evolution.
      Clades 2.3.2.1 and 2.3.4 have become the most dominant lineage in recent years,
      and H5N8 avian influenza outbreaks have been reported Asia. The current approach
      to generate influenza virus vaccines uses embryonated chicken eggs for large
      scale production, although such vaccines have been poorly immunogenic to
      heterologous virus challenge. In the current study, virus-like particles (VLP)
      based on A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) and comprising
      hemagglutinin (HA), neuraminidase (NA), and matrix (M1) were produced using a
      baculovirus expression system to develop effective protection for different H5
      HPAI clade challenges. Mice immunized with VLP demonstrated stronger humoral and
      cellular immune responses than mice immunized with whole influenza virus (WIV),
      with 20-fold higher IgG antibody titers against A/meerkat/Shanghai/SH-1/2012
      after boost. Notably, the WIV vaccine group showed partial protection (80%
      survival) to homologous challenge, little protection (40% survival) to
      heterologous challenge, and 20% survival to H5N8 challenge, whereas all mice in
      the VLP+CFA group survived. These results provide insight for the development of
      effective prophylactic vaccines based on VLPs with cross-clade protection for the
      control of current H5 HPAI outbreaks in humans. 

PMID- 25599604
TI  - Protection of pigs against pandemic swine origin H1N1 influenza A virus infection
      by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus
      recombinants.
AB  - Influenza is an important respiratory disease of pigs, and may lead to novel
      human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV).
      Therefore, improved influenza vaccines for pigs are required. Recently, we
      demonstrated that single intranasal immunization with a hemagglutinin (HA)
      expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba)
      protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we
      investigated enhancement of efficacy by prime-boost vaccination and/or
      intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing
      codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this
      virus was only slightly affected compared to parental virus. Unlike HA, the
      abundantly expressed NA was efficiently incorporated into PrV particles.
      Immunization of pigs with the two PrV recombinants, either singly or in
      combination, induced B cell proliferation and the expected SoIV-specific
      antibodies, whose titers increased substantially after boost vaccination. After
      immunization of animals with either PrV recombinant H1N1 SoIV challenge virus
      replication was significantly reduced compared to PrV-Ba vaccinated or naive
      controls. Protective efficacy of HA-expressing PrV was higher than of NA
      expressing PrV, and not significantly enhanced by combination. Despite higher
      serum antibody titers obtained after intramuscular immunization, transmission of
      challenge virus to naive contact animals was only prevented after intranasal
      prime-boost vaccination with HA-expressing PrV-Ba. 

PMID- 25599605
TI  - Ethanol exposure during gastrulation alters neuronal morphology and behavior in
      zebrafish.
AB  - Ethanol (EtOH) exposure during development has been shown to lead to deficits in
      fine and gross motor control. In this study we used zebrafish embryos to
      determine the effects of EtOH treatment during gastrulation. We treated embryos
      in the gastrulation stage (5.25 hours post fertilization (hpf) to 10.75 hpf) with
      10 mM, 50 mM or 100 mM EtOH and examined the effects on general animal
      morphology, the c-start reflex behavior, Mauthner cell (M-cell) morphology and
      motor neuron morphology. EtOH treated fish exhibited a minor but significant
      increase in gross morphological deformities compared with untreated fish.
      Behavioral studies showed that EtOH treatment resulted in an increase in the peak
      speed of the tail during the escape response. Furthermore, there was a marked
      increase in abnormally directed c-starts, with treated fish showing greater
      incidences of c-starts in inappropriate directions. Immunolabeling of the M
      cells, which are born during gastrulation, revealed that they were significantly
      smaller in fish treated with 100 mM EtOH compared with controls. Immunolabeling
      of primary motor neurons using anti-znp1, showed no significant effect on axonal
      branching, whereas secondary motor axons had a greater number of branches in
      ethanol treated fish compared with controls. Together these findings indicate
      that ethanol exposure during gastrulation can lead to alterations in behavior,
      neuronal morphology and possibly function.

PMID- 25599606
TI  - Long-term behavioral impairment following acute embryonic ethanol exposure in
      zebrafish.
AB  - BACKGROUND: Developmental exposure to ethanol has long been known to cause
      persisting neurobehavioral impairment. However, the neural and behavioral
      mechanisms underlying these deficits and the importance of exposure timing are
      not well-characterized. Given the importance of timing and sequence in
      neurodevelopment it would be expected that alcohol intoxication at different
      developmental periods would result in distinct neurobehavioral consequences.
      METHODS: Zebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8-10 or
      24-27 h post-fertilization (hpf) then reared to adolescence and evaluated on
      several behavioral endpoints. Habituation to a repeated environmental stimulus
      and overall sensorimotor function were assessed using a tap startle test;
      measurements of anxiety and exploration behavior were made following introduction
      to a novel tank; and spatial discrimination learning was assessed using aversive
      control in a three-chambered apparatus. Overt signs of dysmorphogenesis were also
      scored (i.e. craniofacial malformations, including eye diameter and midbrain
      hindbrain boundary morphology). RESULTS: Ethanol treated fish were more active
      both at baseline and following a tap stimulus compared to the control fish and
      were hyperactive when placed in a novel tank. These effects were more prominent
      following exposure at 24-27 hpf than with the earlier exposure window, for both
      dose groups. Increases in physical malformation were only present in the 3%
      ethanol group; all malformed fish were excluded from behavioral testing.
      DISCUSSION: These results suggest specific domains of behavior are affected
      following ethanol exposure, with some but not all of the tests revealing
      significant impairment. The behavioral phenotypes following distinct exposure
      windows described here can be used to help link cellular and molecular mechanisms
      of developmental ethanol exposure to functional neurobehavioral effects.

PMID- 25599607
TI  - Embryonic exposure to cadmium (II) and chromium (VI) induce behavioral
      alterations, oxidative stress and immunotoxicity in zebrafish (Danio rerio).
AB  - Cadmium (Cd) and chromium (Cr) are considered as the main environmental
      contaminants which have serious risks for health. Firstly, we observed that the
      hatchability was significantly decreased by exposure to 10 MUM Cd for 60 and 96 h
      post fertilization (hpf). And some abnormalities in embryos and larvae were
      observed especially in the 10 MUM Cd treated group. Moreover, the free swimming
      activities and the swimming behaviors of the larval zebrafish in response to the
      stimulation of light-to-dark photoperiod transition were significantly influenced
      by both Cd and Cr treatments. Secondly, Cd and Cr exposure induced the changes in
      oxidative stress of the larval zebrafish. The malondialdehyde (MDA) levels
      increased and the glutathione (GSH) contents decreased significantly after the
      exposure to Cd or Cr for 96 hpf. Cd or Cr affected not only the activities of
      superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione S
      transferase (GST), but also the transcriptional levels of their respective genes.
      Thirdly, with regard to the immune response, the mRNA levels of the main
      cytokines including tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6)
      and interleukin-1 beta (IL-1beta) in the larvae increased significantly after the
      exposure to Cd and Cr for 96 hpf. Our results suggested that Cd and Cr have the
      potential to cause behavior alterations, oxidative stress and immunotoxicity in
      the larval zebrafish.

PMID- 25599608
TI  - Acute phase proteins in naturally occurring respiratory disease of feedlot
      cattle.
AB  - The aim of this study was to evaluate three acute phase proteins (APP)
      [haptoglobin (HPT), lipopolysaccharide binding protein (LBP) and transferrin
      (Tf)] in feedlot cattle with naturally occurring respiratory disease diagnosed by
      a calf health scoring chart (CHSC). Seventy-seven beef calves were observed for
      signs of Bovine Respiratory Disease (BRD) during the first 28 days after arrival
      at the feedlot. Fourteen cases and pen matched controls were selected based on
      the CHSC. BRD cases were defined as a score of >= 5, while controls were defined
      as a score <= 4. The mean CHSC score in cases was 6.9 which was significantly
      greater than the controls 2.8 (P < 0.01). Mean plasma LBP and HPT concentrations
      were significantly greater in cases than controls (P < 0.01). Our study results
      show that measurement of HPT and LBP could be useful in detecting respiratory
      disease in feedlot conditions. Transferrin concentrations between the two groups
      were not statistically different.

PMID- 25599610
TI  - Chronology of the Radiographic Appearances of the Calcium Sulfate-Calcium
      Phosphate Synthetic Bone Graft Composite Following Resection of Bone Tumors: A
      Follow-up Study of Postoperative Appearances.
AB  - PURPOSE: The objective of the study was to characterize the radiographic
      appearance of graft resorption and new bone incorporation into a postresection
      defect of the calcium-sulfate calcium-phosphate synthetic bone graft composite
      following resection of benign bone tumours. METHODS: Twenty-five patients who
      underwent treatment with the CaSO4/CaPO4 synthetic graft following bone tumour
      resection were retrospectively identified from our oncology database.
      Postoperative radiographs were assessed for: 1) combined partial graft resorption
      and ingrowth at the graft site; 2) complete graft resorption with complete
      incorporation of new bone into the defect. After chronologically grouping
      radiographs, the volume of graft material used to fill bony defects, radiographic
      evidence of complications, and patterns of resorption were recorded. RESULTS:
      Partial resorption of graft material/partial ingrowth of new bone was seen in 21
      patients at 2.5 months postoperatively. Complete resorption of graft with
      complete new bone incorporation at the graft site was seen in 94% of cases (15 of
      16) by 10 months after surgery. Mean time to complete incorporation of new bone
      was 6.7 months. Time to resorption of the graft with new bone ingrowth was found
      to be related to the volume of graft used with smaller volumes showing earlier
      resorption. For all cases demonstrating resorption (21 of 21), the pattern
      observed was peripheral to central. Five patients developed complications,
      including tumour recurrence, cyst formation, and graft site infection.
      CONCLUSION: Our study suggests a characteristic time and volume related
      radiographic pattern of resorption and new bone ingrowth with the CaSO4/CaPO4
      synthetic graft. Findings that deviate from this pattern may represent
      complication and warrant additional follow-up.

PMID- 25599609
TI  - Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual
      blood-stage lifecycle.
AB  - The malaria parasite Plasmodium falciparum replicates in an intraerythrocytic
      parasitophorous vacuole (PV). The most abundant P. falciparum PV protein, called
      SERA5, is essential in blood stages and possesses a papain-like domain, prompting
      speculation that it functions as a proteolytic enzyme. Unusually however, SERA5
      possesses a Ser residue (Ser596) at the position of the canonical catalytic Cys
      of papain-like proteases, and the function of SERA5 or whether it performs an
      enzymatic role is unknown. In this study, we failed to detect proteolytic
      activity associated with the Ser596-containing parasite-derived or recombinant
      protein. However, substitution of Ser596 with a Cys residue produced an active
      recombinant enzyme with characteristics of a cysteine protease, demonstrating
      that SERA5 can bind peptides. Using targeted homologous recombination in P.
      falciparum, we substituted Ser596 with Ala with no phenotypic consequences,
      proving that SERA5 does not perform an essential enzymatic role in the parasite.
      We could also replace an internal segment of SERA5 with an affinity-purification
      tag. In contrast, using almost identical targeting constructs, we could not
      truncate or C-terminally tag the SERA5 gene, or replace Ser596 with a bulky Arg
      residue. Our findings show that SERA5 plays an indispensable but non-enzymatic
      role in the P. falciparum blood-stage life cycle. 

PMID- 25599613
TI  - Management of sexual dysfunction due to central nervous system disorders: a
      systematic review.
AB  - OBJECTIVE: To systematically review the management of sexual dysfunction due to
      central nervous system (CNS) disorders. PATIENTS AND METHODS: The review was done
      according to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement. Studies were identified independently by two
      reviewers using electronic searches of MEDLINE and OVID (from January 2004 to
      August 2014) and hand searches of reference lists and review articles. RESULTS:
      In patients with CNS disorders, neuro-urological assessment is recommended for
      both genders before starting any treatment for sexual dysfunction. For men, blood
      sexual hormones evaluation is the main investigation performed before
      phosphodiesterase type 5 inhibitors (PDE5Is) treatment, whereas there is no
      consensus on routine laboratory tests for women. PDE5Is are the first-line
      medical treatment for men, with the most robust data derived from patients with
      spinal cord injury assessed by validated questionnaires, mainly the International
      Index of Erectile Function-15. There is no effective medical treatment for sexual
      dysfunction in women. Sacral neuromodulation for lower urinary tract dysfunction
      may improve sexual dysfunction in both genders. CONCLUSIONS: Although sexual
      dysfunction is a major burden for patients with CNS disorders, high-evidence
      level studies are rare and only available for PDE5Is treating erectile
      dysfunction. Well-designed prospective studies are urgently needed for both
      genders.

PMID- 25599611
TI  - Temporal changes in bile acid levels and 12alpha-hydroxylation after Roux-en-Y
      gastric bypass surgery in type 2 diabetes.
AB  - INTRODUCTION: Gastric bypass surgery (GBP) leads to sustained weight loss and
      significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling
      molecules which influence glucose metabolism, are a potential mediator for the
      improvement in T2DM after GBP. This study sought to investigate the effect of GBP
      on BA levels and composition in individuals with T2DM. METHODS: Plasma BA levels
      and composition and fibroblast growth factor (FGF)-19 levels were measured during
      fasting and in response to an oral glucose load before and at 1 month and 2 years
      post GBP in 13 severely obese women with T2DM. RESULTS: A striking temporal
      change in BA levels and composition was observed after GBP. During the fasted
      state, BA concentrations were generally reduced at 1 month, but increased 2 years
      post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an
      exaggerated postprandial peak was observed 2 years after the surgery. A
      significant increase in the 12alpha-hydroxylated/non12alpha-hydroxylated BA ratio
      during fasting and postprandially at 2 years, but not 1 month, post GBP was
      observed. Significant correlations between BAs vs FGF-19, body weight, the
      incretin effect and peptide YY (PYY) were also found. CONCLUSIONS: This study
      provides evidence that GBP temporally modifies the concentration and composition
      of circulating BAs in individuals with T2DM, and suggests that BAs may be linked
      to the improvement in T2DM after GBP.

PMID- 25599615
TI  - ROS and energy metabolism in cancer cells: alliance for fast growth.
AB  - In normal cells, the cellular reactive oxygen species (ROS) level is proportional
      to the activity of mitochondrial electron transport and tightly controlled by
      endogenous antioxidant system. However, energy metabolism and ROS homeostasis in
      cancer cells are much different from those in normal cells. For example, a
      majority of cellular glucose is metabolized through aerobic glycolysis ("Warburg
      effect") and the pentose phosphate pathway. Cancer cells harbor functional
      mitochondria, but many mutations in nuclear DNA-encoded mitochondrial genes and
      mitochondrial genome result in the mitochondrial metabolic reprogramming. The
      other characteristic of cancer cells is to maintain much higher ROS level than
      normal cells. Ironically, cancer cells overexpress the ROS-producing NADPH
      oxidase and the ROS-eliminating antioxidant enzymes, both of which enzyme systems
      share NADPH as a reducing power source. In this article, we review the complex
      connection between ROS and energy metabolisms in cancer cells. 

PMID- 25599612
TI  - Circulating FGF19 and FGF21 surge in early infancy from infra- to supra-adult
      concentrations.
AB  - BACKGROUND/OBJECTIVE: Fibroblast growth factor 19 (FGF19) and 21 (FGF21) have
      been linked to obesity and type 2 diabetes in adults. We assessed the circulating
      concentrations of these factors in human neonates and infants, and their
      association with the endocrine-metabolic changes associated to prenatal growth
      restraint. SUBJECTS/METHODS: Circulating FGF19 and FGF21, selected hormones
      (insulin, insulin-like growth factor I and high- molecular-weight (HMW)
      adiponectin) and body composition (absorptiometry) were assessed longitudinally
      in 44 infants born appropriate- (AGA) or small-for-gestational-age (SGA).
      Measurements were performed at 0, 4 and 12 months in AGA infants; at 0 and 4
      months in SGA infants; and cross-sectionally in 11 first-week AGA newborns.
      RESULTS: Circulating FGF19 and FGF21 surged >10-fold in early infancy from infra-
      to supra-adult concentrations, the FGF19 surge appearing slower and more
      pronounced than the FGF21 surge. Whereas the FGF21 surge was of similar magnitude
      in AGA and SGA infants, FGF19 induction was significantly reduced in SGA infants.
      In AGA and SGA infants, cord-blood FGF21 and serum FGF19 at 4 months showed a
      positive correlation with HMW adiponectin (r=0.49, P=0.013; r=0.43, P=0.019,
      respectively). CONCLUSIONS: Our results suggest that these early FGF19 and FGF21
      surges are of a physiological relevance that warrants further delineation and
      that may extend beyond infancy.

PMID- 25599614
TI  - IFPA senior award lecture: Energy metabolism of human placental tissue studied by
      ex vivo perfusion of an isolated cotyledon.
AB  - BACKGROUND: This is a historical review of the method of "Ex vivo dual perfusion
      of a human placental cotyledon", which was first described by M. Panigel in 1967.
      The subsequent evolution of this method is described with particular emphasis on
      energy metabolism of human placental tissue under ex vivo conditions. METHOD: For
      perfusion of the foetal compartment a pair of a chorionic arterial and venous
      vessel is cannulated. In the original method a remnant of the spiral artery of
      that cotyledon was catheterized to provide access to the maternal compartment. To
      simplify the procedure access to the intervillous space later was achieved by
      penetration of the decidual plate with 3 to 5 cannulae. RESULTS: Due to a
      remarkable tolerance of ischaemia energy dependent transport of amino acids and
      de novo synthesis of proteins remain functional in spite of a delay of 20 to 30
      min. until start of the two ex vivo circuits. With medium containing only
      physically dissolved oxygen the high demand of oxygen of the tissue can only
      partially be met. Chronic hypoxia leads to metabolic reprogramming with reduction
      in mitochondrial oxygen consumption and an increase in anaerobic glycolysis.
      Addition of erythrocytes to the medium is highly effective in increasing oxygen
      supply at physiological partial pressure with stimulation of aerobic glycolysis
      and de novo synthesis of proteins. Increasing the number of maternal cannulae
      leads to a better distribution of haemoglobin free medium with physiological
      partial pressure of oxygen giving median values of oxygen content inside the
      intervillous space close to target values. CONCLUSION: Ex vivo dual perfusion of
      a human placental cotyledon allows to study functional aspects of this organ
      under close to in vivo conditions. A remarkable tolerance of ischaemia permits a
      start of dual perfusion ex vivo with a delay of 20 to 30 min. after delivery
      without significant tissue damage.

PMID- 25599616
TI  - Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a
      high affinity niacin receptor.
AB  - Even though nicotinic acid (niacin) appears to have beneficial effects on human
      lipid profiles, niacin-induced cutaneous vasodilatation called flushing limits
      its remedy to patient. GPR109A is activated by niacin and mediates the anti
      lipolytic effects. Based on the hypothesis that beta-arrestin signaling mediates
      niacin-induced flushing, but not its anti-lipolytic effect, we tried to find
      GPR109A agonists which selectively elicit Gi-protein-biased signaling devoid of
      beta-arrestin internalization using a beta-lactamase assay. We identified a 4
      (phenyl)thio-1H-pyrazole as a novel scaffold for GPR109A agonist in a high
      throughput screen, which has no carboxylic acid moiety known to be important for
      binding. While 1-nicotinoyl derivatives (5a-g, 6a-e) induced beta-arrestin
      recruitment, 1-(pyrazin-2-oyl) derivatives were found to play as G-protein-biased
      agonists without GPR109A receptor internalization. The activity of compound 5a
      (EC50 = 45 nM) was similar to niacin (EC50 = 52 nM) and MK-6892 (EC50 = 74 nM) on
      calcium mobilization assay, but its activity at 10 MUM on beta-arrestin
      recruitment were around two and five times weaker than niacin and MK-6892,
      respectively. The development of G-protein biased GPR109A ligands over beta
      arrestin pathway is attainable and might be important in differentiation of
      pharmacological efficacy.

PMID- 25599617
TI  - Clinical trials: New nonabsorbable potassium-exchange resins in hyperkalaemia.

PMID- 25599619
TI  - Clinical trials. Rituximab for maintenance of remission in AAV.
AB  - Maintenance therapy for antineutrophil cytoplasmic antibody-associated vasculitis
      (AAV) should reduce rates of relapse with minimal toxicity. The MAINRITSAN trial
      the first randomized controlled trial to compare the efficacies of rituximab and
      azathioprine in AAV remission maintenance- has demonstrated a superior outcome
      using rituximab. These data have important implications for the management of
      AAV.

PMID- 25599620
TI  - Hyponatraemia: Isotonic fluids prevent hospital-acquired hyponatraemia.

PMID- 25599622
TI  - Clinical trials. Renal safety of TDF as pre-exposure prophylaxis for HIV-1
      infection.

PMID- 25599623
TI  - Diabetes. Excess mortality in well-controlled T1DM without renal disease.
AB  - The authors of a new study report that independent of renal disease, any level of
      glycaemia is associated with increased mortality risk in patients with type 1
      diabetes mellitus. However, this view may be overly simplistic-a multifactorial
      approach is required to reduce excess mortality in this population.

PMID- 25599618
TI  - Birth weight, malnutrition and kidney-associated outcomes--a global concern.
AB  - An adverse intrauterine environment is associated with an increased risk of
      elevated blood pressure and kidney disease in later life. Many studies have
      focused on low birth weight, prematurity and growth restriction as surrogate
      markers of an adverse intrauterine environment; however, high birth weight,
      exposure to maternal diabetes and rapid growth during early childhood are also
      emerging as developmental risk factors for chronic diseases. Altered programming
      of nephron number is an important link between exposure to developmental
      stressors and subsequent risk of hypertension and kidney disease. Maternal,
      fetal, and childhood nutrition are crucial contributors to these programming
      effects. Resource-poor countries experience the sequential burdens of fetal and
      childhood undernutrition and subsequent overnutrition, which synergistically act
      to augment the effects of developmental programming; this observation might
      explain in part the disproportionate burden of chronic disease in these regions.
      Numerous nutritional interventions have been effective in reducing the short-term
      risk of low birth weight and prematurity. Understanding the potential long-term
      benefits of such interventions is crucial to inform policy decisions to interrupt
      the developmental programming cycle and stem the growing epidemics of
      hypertension and kidney disease worldwide. 

PMID- 25599624
TI  - Reliability of store and forward teledermatology for skin neoplasms.
AB  - BACKGROUND: Teledermatology may be less optimal for skin neoplasms than for
      rashes. OBJECTIVES: We sought to determine agreement for skin neoplasms. METHODS:
      This was a repeated measures study. Each lesion was examined by a clinic
      dermatologist and a teledermatologist; both generated a primary diagnosis, up to
      2 differential diagnoses, and management. Macro images and polarized light
      dermoscopy images were obtained; for pigmented lesions only, contact immersion
      dermoscopy image was obtained. RESULTS: There were 3021 lesions in 2152 patients.
      Of 1685 biopsied lesions, there were 410 basal cell carcinomas (24%), 240
      squamous cell carcinomas (14%), and 41 melanomas (2.4%). Agreement was fair to
      substantial for primary diagnosis (45.7%-80.1%; kappa 0.32-0.62), substantial to
      almost perfect for aggregated diagnoses (primary plus differential; 78.6%-93.9%;
      kappa 0.77-0.90), and fair for management (66.7%-86.1%; kappa 0.28-0.41).
      Diagnostic agreement rates were higher for pigmented lesions (52.8%-93.9%; kappa
      0.44-0.90) than nonpigmented lesions (47.7%-87.3%; kappa 0.32-0.86), whereas the
      reverse was found for management agreement (pigmented: 66.7%-79.8%, kappa 0.19
      0.35 vs nonpigmented: 72.0%-86.1%, kappa 0.38-0.41). Agreement rates using macro
      images were similar to polarized light dermoscopy; contact immersion dermoscopy,
      however, significantly improved rates for pigmented lesions. LIMITATIONS: We
      studied a homogeneous population. CONCLUSIONS: Diagnostic agreement was moderate
      to almost perfect whereas management agreement was fair. Polarized light
      dermoscopy increased rates modestly whereas contact immersion dermoscopy
      significantly increased rates for pigmented lesions.

PMID- 25599621
TI  - Podocyte dysfunction in atypical haemolytic uraemic syndrome.
AB  - Genetic or autoimmune defects that lead to dysregulation of the alternative
      pathway of complement have been associated with the development of atypical
      haemolytic uraemic syndrome (aHUS), which is characterized by thrombocytopenia,
      haemolytic anaemia and acute kidney injury. The relationship between aHUS,
      podocyte dysfunction and the resultant proteinuria has not been adequately
      investigated. However, the report of mutations in diacylglycerol kinase epsilon
      (DGKE) as a cause of recessive infantile aHUS characterized by proteinuria,
      highlighted podocyte dysfunction as a potential complication of aHUS. DGKE
      deficiency was originally thought to trigger aHUS through pathogenetic mechanisms
      distinct from complement dysregulation; however, emerging findings suggest an
      interplay between DGKE and complement systems. Podocyte dysfunction with
      nephrotic-range proteinuria can also occur in forms of aHUS associated with
      genetic or autoimmune complement dysregulation without evidence of DGKE
      mutations. Furthermore, proteinuric glomerulonephritides can be complicated by
      aHUS, possibly as a consequence of podocyte dysfunction inducing endothelial
      injury and prothrombotic abnormalities. 

PMID- 25599625
TI  - Evaluation of the ScopeControl endoscope test system in six hospitals in The
      Netherlands.
AB  - As rigid endoscopes are re-used after minimal invasive surgery, they degrade over
      time. To guarantee the optical quality of a rigid endoscope, the ScopeControl has
      been developed to measure key optical parameters such as, light transmission
      (LT), color correctness (CC), focus (FC), fiber transmission (FT), viewing angle
      (VA) and field of view (FV). To evaluate the performance of the ScopeControl,
      five ScopeControls SV (study version) have been tested in six hospitals in the
      Netherlands. Aspects such as robustness, precision, usability of the measured
      data, acceptation criteria and ergonomic aspects have been assessed. The
      ScopeControl maintains its stability over time and can measure LT, CC and FC with
      5% precision, VA and FV with 2% accuracy and FT with 10% precision. The final
      thresholds above which an endoscope could still be considered to be in good
      condition, appeared to be: VA at 75%, CC, FC and FV at 70%, LT at 65% and FT at
      35% of that of the best endoscope of that type ever found. The ScopeControl SV
      fits the workflow of the sterilization department as it is easy to use and can
      easily be cleaned. The time to perform a measurement is 2-3 min (one minute is
      spent to select the correct endoscope). The ScopeControl PV (launched in November
      2013), has been used clinically from April to November 2014. It proves to be more
      stable, well accepted by personnel from the sterilization department and be of
      large value of preventing defect endoscopes on the surgery table. 

PMID- 25599626
TI  - Effects of TNFalpha inhibitors on adiposity and other cardiovascular risk
      factors: implications for the cardiovascular prognosis in patients with
      rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is
      associated with increased cardiovascular (CV) morbidity and mortality. This
      increased CV burden is the result of an enhanced prevalence of traditional CV
      risk factors, the effects of treatments given for RA but also systemic
      inflammation. In this setting, the control of inflammation by the current
      therapeutic approach may improve the overall CV prognosis of RA. AREAS COVERED:
      This paper analyses the impact of TNFalpha inhibitors on the different CV risk
      factors with a special emphasis on lipid profile and body composition. The lipid
      profile under TNFalpha inhibitors changes, an increase in total and high density
      lipoprotein (HDL) cholesterol is observed but the atherogenic index and low
      density lioprotein cholesterol are unaffected. In parallel, TNFalpha inhibitors
      induce an accumulation of fat in the abdominal/visceral region. Analysis of
      cohort and registry studies indicates that CV events are reduced under this
      treatment. EXPERT OPINION: Overall, the favourable CV effect under TNFalpha
      inhibitors does not seem to be explained by the changes in traditional CV risk
      factors, but rather by the improvement in systemic inflammation. Alternatively,
      the changes in body composition raise the question of their effect on long-term
      CV safety.

PMID- 25599627
TI  - Exploring the Far Side of Mobile Health: Information Security and Privacy of
      Mobile Health Apps on iOS and Android.
AB  - BACKGROUND: Mobile health (mHealth) apps aim at providing seamless access to
      tailored health information technology and have the potential to alleviate global
      health burdens. Yet, they bear risks to information security and privacy because
      users need to reveal private, sensitive medical information to redeem certain
      benefits. Due to the plethora and diversity of available mHealth apps,
      implications for information security and privacy are unclear and complex.
      OBJECTIVE: The objective of this study was to establish an overview of mHealth
      apps offered on iOS and Android with a special focus on potential damage to users
      through information security and privacy infringements. METHODS: We assessed apps
      available in English and offered in the categories "Medical" and "Health &
      Fitness" in the iOS and Android App Stores. Based on the information retrievable
      from the app stores, we established an overview of available mHealth apps, tagged
      apps to make offered information machine-readable, and clustered the discovered
      apps to identify and group similar apps. Subsequently, information security and
      privacy implications were assessed based on health specificity of information
      available to apps, potential damage through information leaks, potential damage
      through information manipulation, potential damage through information loss, and
      potential value of information to third parties. RESULTS: We discovered 24,405
      health-related apps (iOS; 21,953; Android; 2452). Absence or scarceness of
      ratings for 81.36% (17,860/21,953) of iOS and 76.14% (1867/2452) of Android apps
      indicates that less than a quarter of mHealth apps are in more or less widespread
      use. Clustering resulted in 245 distinct clusters, which were consolidated into
      12 app archetypes grouping clusters with similar assessments of potential damage
      through information security and privacy infringements. There were 6426 apps that
      were excluded during clustering. The majority of apps (95.63%, 17,193/17,979; of
      apps) pose at least some potential damage through information security and
      privacy infringements. There were 11.67% (2098/17,979) of apps that scored the
      highest assessments of potential damages. CONCLUSIONS: Various kinds of mHealth
      apps collect and offer critical, sensitive, private medical information, calling
      for a special focus on information security and privacy of mHealth apps. In order
      to foster user acceptance and trust, appropriate security measures and processes
      need to be devised and employed so that users can benefit from seamlessly
      accessible, tailored mHealth apps without exposing themselves to the serious
      repercussions of information security and privacy infringements.

PMID- 25599628
TI  - Mercury distribution, methylation and volatilization in microcosms with and
      without the sea anemone Bunodosoma caissarum.
AB  - Mercury (Hg) has a complex biogeochemical cycle in aquatic environments. Its most
      toxic form, methylmercury (MeHg), is produced by microorganisms. This study
      investigated how the sea anemone Bunodosoma caissarum affects Hg distribution,
      methylation and volatilization in laboratory model systems. (203)Hg was added to
      microcosms and its distribution in seawater, specimens and air was periodically
      measured by gamma spectrometry. MeHg was measured by liquid scintillation. After
      the uptake period, specimens had a bioconcentration factor of 70 and in
      microcosms with and without B. caissarum, respectively 0.05% and 0.32% of the
      initial spike was found as MeHg. After depuration, MeHg in specimens ranged from
      0.2% to 2.4% of total Hg. Microcosms with B. caissarum had higher Hg
      volatilization (58%) than controls (17%), possibly due to Hg(2+) reduction
      mediated by microorganisms associated with its tissues and mucus secretions.
      Marine organisms and their associated microbiota may play a role in Hg and MeHg
      cycling. 

PMID- 25599630
TI  - Piling underwater noise impact on migrating salmon fish during Lithuanian LNG
      terminal construction (Curonian Lagoon, Eastern Baltic Sea Coast).
AB  - Development of human activities in the Klaipeda strait generates a wide spectrum
      of underwater noise. In the fall of 2013, at the liquid natural gas terminal
      construction site in the shallow Curonian Lagoon area, an assessment of possible
      negative impacts on migrating salmon fish caused by pile driving noise was made.
      It is well known that impact hammer pile driving generates pulses with extremely
      high underwater noise levels. The obtained results proved that the pile hammering
      into the lagoon bottom generated pulses with a sound exposure level of 218 dB re
      1 MUPa(2) s @1m thus posing a risk to the migrating fish.

PMID- 25599629
TI  - Wetland plants as indicators of heavy metal contamination.
AB  - In this study metal accumulating abilities of three emergent macrophytes
      (Phragmites australis, Typha capensis and Spartina maritima) were investigated in
      the urbanised Swartkops Estuary. Plants and sediment samples were collected at
      seven sites along the banks of the main channel and in adjacent canals. Sediments
      and plant organs were analysed, by means of atomic absorption spectrometry, for
      four elements (Cd, Cu, Pb, and Zn). Metal concentrations in the sediments of
      adjacent canals were found to be substantially higher than those at sites along
      the banks of the estuary. These differences were reflected in the plant organs
      for Pb and Zn, but not for Cu and Cd. All three species exhibited significantly
      higher concentrations of metals in their roots. These species are therefore
      suitable for use as indicators of the presence and level of heavy metal
      contaminants in estuaries. 

PMID- 25599632
TI  - Introduction of the alien Xenostrobus securis (Bivalvia: Mytilidae) into Hong
      Kong, China: interactions with and impacts upon native species and the earlier
      introduced Mytilopsis sallei (Bivalvia: Dreissenidae).
AB  - This constitutes the first record of the Australian alien mytilid Xenostrobus
      securis in China. The introduction occurred prior to 2010 probably via shipping
      arriving at Yantian in Mirs Bay, China, close to Hong Kong. Point sources of
      infection could be Australia or Korea or Japan where it has similarly been
      introduced. Analysis of X. securis in Hong Kong shows that it tolerates a wide
      range of salinities from 5.40/00 to 28.70/00. Water temperatures in Hong Kong
      match those in its native range. In Hong Kong, X. securis co-occurs with the
      similarly introduced Mytilopsis sallei and a native bivalve community. The
      population structure of X. securis suggests a lifespan of >2 years with new
      generations produced by conspecifics. Such a life history strategy is also
      exhibited by M. sallei. Now established in China, northern Asia, the
      Mediterranean and, most recently, the Iberian Atlantic, the invasion of other
      locations by X. securis seems probable.

PMID- 25599631
TI  - Recommendations to design environmental monitoring in the European bullhead,
      Cottus sp., based on reproductive cycle and immunomarker measurement.
AB  - European bullhead is a relevant fish species to assess adverse effects of
      environmental stress on wild fish. Nevertheless, their complex reproductive cycle
      is very different between sites and could interfere with many physiological
      processes. Thus, prior to use biomarker to statute on environmental quality of
      rivers, we wanted to characterize reproductive profile (spawn number, GSI, gonad
      development). The major results demonstrated that the two types of reproductive
      cycle shown were strongly correlated to water temperature variation. In a second
      time, even if innate immunomarkers are highly relevant on biomonitoring program,
      hormonal variation seems to impact severely their responses. Thus, the link
      between reproductive status and immune activity (leucocyte distribution, cellular
      mortality, respiratory burst, phagocytosis activity) must also be study.
      Nonetheless, in the present work, immune capacities seems to be more correlated
      with season and environmental factors than reproduction. 

PMID- 25599633
TI  - Towards establishment of GeoHealth, an open-data portal for health mapping and
      modelling based on Earth observations by remote sensing.

PMID- 25599634
TI  - Estimating the global abundance of ground level presence of particulate matter
      (PM2.5).
AB  - With the increasing awareness of the health impacts of particulate matter, there
      is a growing need to comprehend the spatial and temporal variations of the global
      abundance of ground level airborne particulate matter with a diameter of 2.5
      microns or less (PM2.5). Here we use a suite of remote sensing and meteorological
      data products together with ground-based observations of particulate matter from
      8,329 measurement sites in 55 countries taken 1997-2014 to train a machine
      learning algorithm to estimate the daily distributions of PM2.5 from 1997 to the
      present. In this first paper of a series, we present the methodology and global
      average results from this period and demonstrate that the new PM2.5 data product
      can reliably represent global observations of PM2.5 for epidemiological studies.

PMID- 25599635
TI  - GeoMedStat: an integrated spatial surveillance system to track air pollution and
      associated healthcare events.
AB  - Air pollutants, such as particulate matter with a diameter <=2.5 microns (PM2.5)
      and ozone (O3), are known to exacerbate asthma and other respiratory diseases. An
      integrated surveillance system that tracks such air pollutants and associated
      disease incidence can assist in risk assessment, healthcare preparedness and
      public awareness. However, the implementation of such an integrated environmental
      health surveillance system is a challenge due to the disparate sources of many
      types of data and the implementation becomes even more complicated for a spatial
      and real-time system due to lack of standardised technological components and
      data incompatibility. In addition, accessing and utilising health data that are
      considered as Protected Health Information (PHI) require maintaining stringent
      protocols, which have to be supported by the system. This paper aims to
      illustrate the development of a spatial surveillance system (GeoMedStat) that is
      capable of tracking daily environmental pollutants along with both daily and
      historical patient encounter data. It utilises satellite data and the
      groundmonitor data from the US National Aeronautics and Space Administration
      (NASA) and the US Environemental Protection Agenecy (EPA), rspectively as inputs
      estimating air pollutants and is linked to hospital information systems for
      accessing chief complaints and disease classification codes. The components,
      developmental methods, functionality of GeoMedStat and its use as a real-time
      environmental health surveillance system for asthma and other respiratory
      syndromes in connection with with PM2.5 and ozone are described. It is expected
      that the framework presented will serve as an example to others developing real
      time spatial surveillance systems for pollutants and hospital visits. 

PMID- 25599636
TI  - Redefining climate regions in the United States of America using satellite remote
      sensing and machine learning for public health applications.
AB  - Existing climate classification has not been designed for an efficient handling
      of public health scenarios. This work aims to design an objective spatial climate
      regionalization method for assessing health risks in response to extreme weather.
      Specific climate regions for the conterminous United States of America (USA) were
      defined using satellite remote sensing (RS) data and compared with the
      conventional Koppen-Geiger (KG) divisions. Using the nationwide database of
      hospitalisations among the elderly (>=65 year olds), we examined the utility of a
      RS-based climate regionalization to assess public health risk due to extreme
      weather, by comparing the rate of hospitalisations in response to thermal
      extremes across climatic regions. Satellite image composites from 2002-2012 were
      aggregated, masked and compiled into a multi-dimensional dataset. The
      conterminous USA was classified into 8 distinct regions using a stepwise
      regionalization approach to limit noise and collinearity (LKN), which exhibited a
      high degree of consistency with the KG regions and a well-defined regional
      delineation by annual and seasonal temperature and precipitation values. The most
      populous was a temperate wet region (10.9 million), while the highest rate of
      hospitalisations due to exposure to heat and cold (9.6 and 17.7 cases per 100,000
      persons at risk, respectively) was observed in the relatively warm and humid
      south-eastern region. RS-based regionalization demonstrates strong potential for
      assessing the adverse effects of severe weather on human health and for decision
      support. Its utility in forecasting and mitigating these effects has to be
      further explored. 

PMID- 25599637
TI  - Using geographical information systems for defining the accessibility to health
      care facilities in Jeddah City, Saudi Arabia.
AB  - Spatial data play an important role in the planning of health care facilities and
      their allocation. Today, geographical information systems (GIS) provide useful
      techniques for capturing, maintaining and analysing health care spatial data;
      indeed health geoinformatics is an emerging discipline that uses innovative
      geospatial technology to investigate health issues. The purpose of this paper is
      to define how GIS can be used for assessing the level of accessibility to health
      care. The paper identifies the advantages of using GIS in health care planning
      and covers GIS-based international accessibility with a focus on GIS applications
      for health care facilities in Jeddah city, Saudi Arabia. A geodatabase that
      includes location of health services, road networks, health care demand and
      population districts was created using ArcGIS software. The geodatabase produced
      is based on collected data and covers issues, such as defining the spatial
      distribution of health care facilities, evaluating health demand types and
      modelling health service areas based on analysis of driving-time and straight
      line distances. 

PMID- 25599638
TI  - Fine-scale mapping of vector habitats using very high resolution satellite
      imagery: a liver fluke case-study.
AB  - The visualization of vector occurrence in space and time is an important aspect
      of studying vector-borne diseases. Detailed maps of possible vector habitats
      provide valuable information for the prediction of infection risk zones but are
      currently lacking for most parts of the world. Nonetheless, monitoring vector
      habitats from the finest scales up to farm level is of key importance to refine
      currently existing broad-scale infection risk models. Using Fasciola hepatica, a
      parasite liver fluke, as a case in point, this study illustrates the potential of
      very high resolution (VHR) optical satellite imagery to efficiently and semi
      automatically detect detailed vector habitats. A WorldView2 satellite image
      capable of <5m resolution was acquired in the spring of 2013 for the area around
      Bruges, Belgium, a region where dairy farms suffer from liver fluke infections
      transmitted by freshwater snails. The vector thrives in small water bodies
      (SWBs), such as ponds, ditches and other humid areas consisting of open water,
      aquatic vegetation and/or inundated grass. These water bodies can be as small as
      a few m2 and are most often not present on existing land cover maps because of
      their small size. We present a classification procedure based on object-based
      image analysis (OBIA) that proved valuable to detect SWBs at a fine scale in an
      operational and semi-automated way. The classification results were compared to
      field and other reference data such as existing broad-scale maps and expert
      knowledge. Overall, the SWB detection accuracy reached up to 87%. The resulting
      fine-scale SWB map can be used as input for spatial distribution modelling of the
      liver fluke snail vector to enable development of improved infection risk mapping
      and management advice adapted to specific, local farm situations.

PMID- 25599639
TI  - Mapping urban and peri-urban breeding habitats of Aedes mosquitoes using a fuzzy
      analytical hierarchical process based on climatic and physical parameters.
AB  - The spread of dengue fever depends mainly on the availability of favourable
      breeding sites for its mosquito vectors around human dwellings. To investigate if
      the various factors influencing breeding habitats can be mapped from space,
      dengue indices, such as the container index, the house index and the Breteau
      index, were calculated from Ministry of Public health data collected three times
      annually in Phitsanulok, Thailand between 2009 and 2011. The most influential
      factors were found to be temperature, humidity, rainfall, population density,
      elevation and land cover. Models were worked out using parameters mostly derived
      from freely available satellite images and fuzzy logic software with parameter
      synchronisation and a predication algorithm based on data mining and the Decision
      Tree method. The models developed were found to be sufficiently flexible to
      accommodate additional parameters and sampling data that might improve prediction
      of favourable breeding hotspots. The algorithm applied can not only be used for
      the prediction of near real-time scenarios with respect to dengue, but can also
      be applied for monitoring other diseases influenced by environmental and climatic
      factors. The multi-criteria model presented is a cost-effective way of
      identifying outbreak hotspots and early warning systems lend themselves for
      development based on this strategy. The proposed approach demonstrates the
      successful utilisation of remotely sensed images to map mosquito breeding
      habitats. 

PMID- 25599640
TI  - Indirect field technology for detecting areas object of illegal spills harmful to
      human health: application of drones, photogrammetry and hydrological models.
AB  - The accumulation of heavy metals in agricultural soils is a serious environmental
      problem. The Campania region in southern Italy has higher levels of cancer risk,
      presumably due to the accumulation of geogenic and anthropogenic soil pollutants,
      some of which have been incorporated into organic matter. The aim of this study
      was to introduce and test an innovative, field-applicable methodology to detect
      heavy metal accumulation using drone-based photogrammetry and microrill network
      modelling, specifically to generate wetlands wetlands prediction indices normally
      applied at large catchment scales, such as a large geographic basin. The
      processing of aerial photos taken using a hexacopter equipped with fifth
      generation software for photogrammetry allowed the generation of a digital
      elevation model (DEM) with a resolution as high as 30 mm. Not only this provided
      a high potential for the study of micro-rill processes, but it was also useful
      for testing and comparing the capability of the topographic index (TI) and the
      clima-topographic index (CTI) to predict heavy metal sedimentation points at
      scales from 0.1 to 10 ha. Our results indicate that the TI and CTI indices can be
      used to predict points of heavy metal accumulation for small field catchments. 

PMID- 25599641
TI  - Japan's efforts to promote global health using satellite remote sensing data from
      the Japan Aerospace Exploration Agency for prediction of infectious diseases and
      air quality.
AB  - In this paper we review the status of new applications research of the Japanese
      Aerospace Exploration Agency (JAXA) for global health promotion using information
      derived from Earth observation data by satellites in cooperation with inter
      disciplinary collaborators. Current research effort at JAXA to promote global
      public health is focused primarily on the use of remote sensing to address two
      themes: (i) prediction models for malaria and cholera in Kenya, Africa; and (ii)
      air quality assessment of small, particulate matter (PM2.5), nitrogen dioxide
      (NO2) and ozone (O3). Respiratory and cardivascular diseases constitute cross
      boundary public health risk issues on a global scale. The authors report here on
      results of current of a collaborative research to call attention to the need to
      take preventive measures against threats to public health using newly arising
      remote sensing information from space. 

PMID- 25599643
TI  - Bortezomib-resistant mutant proteasomes: structural and biochemical evaluation
      with carfilzomib and ONX 0914.
AB  - Inhibition of the 20S proteasome by bortezomib (Velcade) constitutes a
      successfully applied therapy for blood cancer. However, emerging resistance
      restricts its medicinal use. For example, mutations in the proteolytically active
      beta5-subunit of the proteasome, the main target of inhibitors, were reported to
      impair drug binding and thus to reduce therapeutic efficacy. Using yeast as a
      model system, we describe here a systematic evaluation of these mutations by cell
      growth analysis, proteasome inhibition assays, and X-ray crystallography. The 11
      mutants examined display decreased proliferation rates, impaired proteolytic
      activity, and marked resistance to bortezomib as well as the alpha',beta'
      epoxyketone inhibitors carfilzomib (Kyprolis) and ONX 0914, while the second
      generation compound carfilzomib was the least affected. In total, 49 proteasome X
      ray structures, including structural data on proteasome-carfilzomib complexes,
      reveal three distinct molecular mechanisms that hamper both drug binding and
      natural substrate turnover to an extent that is still compatible with cell
      survival. 

PMID- 25599642
TI  - Structural and evolutionary analyses show unique stabilization strategies in the
      type IV pili of Clostridium difficile.
AB  - Type IV pili are produced by many pathogenic Gram-negative bacteria and are
      important for processes as diverse as twitching motility, biofilm formation,
      cellular adhesion, and horizontal gene transfer. However, many Gram-positive
      species, including Clostridium difficile, also produce type IV pili. Here, we
      identify the major subunit of the type IV pili of C. difficile, PilA1, and
      describe multiple 3D structures of PilA1, demonstrating the diversity found in
      three strains of C. difficile. We also model the incorporation of both PilA1 and
      a minor pilin, PilJ, into the pilus fiber. Although PilA1 contains no cysteine
      residues, and therefore cannot form the disulfide bonds found in all Gram
      negative type IV pilins, it adopts unique strategies to achieve a typical pilin
      fold. The structures of PilA1 and PilJ exhibit similarities with the type IVb
      pilins from Gram-negative bacteria that suggest that the type IV pili of C.
      difficile are involved in microcolony formation.

PMID- 25599644
TI  - Crystal structure of the human 20S proteasome in complex with carfilzomib.
AB  - Proteasome inhibition is highly effective as a treatment for multiple myeloma,
      and recently carfilzomib was granted US FDA approval for the treatment of
      relapsed and refractory multiple myeloma. Here, we report the X-ray crystal
      structure of the human constitutive 20S proteasome with and without carfilzomib
      bound at 2.9 and 2.6 A, respectively. Our data indicate that the S3 and S4
      binding pockets play a pivotal role in carfilzomib's selectivity for chymotrypsin
      like sites. Structural comparison with the mouse immunoproteasome crystal
      structure reveals amino acid substitutions that explain carfilzomib's slight
      preference for chymotrypsin-like subunits of constitutive proteasomes. In
      addition, comparison of the human proteasome:carfilzomib complex with the mouse
      proteasome:PR-957 complex reveals new details that explain why PR-957 is
      selective for immunoproteasomes. Together, the data presented here support the
      design of inhibitors for either constitutive or immunoproteasomes, with
      implications for the treatment of cancers as well as autoimmune and
      neurodegenerative diseases.

PMID- 25599646
TI  - Speciation of fluoride in workroom air during primary production of aluminium.
AB  - Exposure to fluorides (F(-)) and particulate matter (PM) was assessed by personal
      sampling with use of Respicon(r) sampler in Prebake and Soderberg pot rooms in
      seven aluminium smelters. The inhalable PM mass was dominated by the extra
      thoracic aerosol sub-fraction, which contributed with around 70% for both Prebake
      and Soderberg pot room workers. Quantitative and qualitative differences in
      exposure were found between pot room workers in smelters using these two
      technologies. Prebake pot room workers were exposed to 1.4 to 1.7 times higher PM
      concentrations than Soderberg pot room workers, depending on aerosol sub
      fraction. Prebake pot room workers were also exposed to 2.5 to 2.9 higher air
      concentrations of water-soluble F(-) (FWS(-)) and 2.8 to 5.3 higher air
      concentrations of non water-soluble F(-) (FAS(-)) than Soderberg pot room
      workers, depending on aerosol sub-fraction. However, exposure to hydrogen
      fluoride (HF) was 1.3 times higher among Soderberg pot room workers. The relative
      amount of FWS(-), however, was higher among Soderberg pot room workers, while the
      relative amount of particulate F(-) (sum of FWS(-) and FAS(-)) was higher among
      Prebake pot room workers (6.5 vs. 3.9%). Exposure to the same PM concentration
      yielded higher FWS(-) and FAS(-) air concentrations among Prebake compared to
      Soderberg pot room workers. 

PMID- 25599645
TI  - Molecular determinants for nuclear import of influenza A PB2 by importin alpha
      isoforms 3 and 7.
AB  - Influenza A virus polymerase subunit PB2 is a major virulence determinant
      implicated in pathogenicity and host adaptation. During cross-species virus
      transfer from avian to mammalian cells, PB2 switches specificity from importin
      alpha3 to alpha7. This specificity is not recapitulated in vitro, where PB2 binds
      all importin alpha isoforms with comparably high affinity. In this study, we
      investigated the structure, conformational dynamics, and autoinhibition of
      importin alpha isoforms 1, 3, and 7 in complex with PB2. Our data suggest that
      association of PB2 with alpha3 and alpha7 is favored by reduced autoinhibition of
      these isoforms and by the unique structure of the nuclear localization signal
      (NLS) domain of PB2. We propose that by recruiting importin alpha3 or alpha7 in
      the absence of importin beta, PB2 reduces the complexity of adaptor-mediated
      import to a pseudo-bimolecular reaction, thereby acquiring a kinetic advantage
      over classical NLS cargos, which form an import complex only when importin alpha
      and beta are simultaneously available.

PMID- 25599647
TI  - Lack of association between the CDH1 polymorphism and gastric cancer
      susceptibility: a meta-analysis.
AB  - E-Cadherin (CDH1) plays a key role in cell adhesion, which is vital to the normal
      development and maintenance of cells. Down regulation of CDH1, may lead to
      dysfunction of the cell-cell adhesion system, resulting in increased
      susceptibility to tumor development and subsequent tumor cell invasion and
      metastasis. The CDH1 C-160A polymorphism could decrease its transcription
      efficiency and may increase susceptibility to cancer development, but its
      relevance to gastric cancer is generally disputed. Consequently, we performed a
      meta-analysis of published case-control studies, including 4218 gastric cancer
      cases and 5461 controls. Overall, no significant association was observed between
      the CDH1 C-160A polymorphism and risk of gastric cancer in all genetic models. In
      the stratified analysis by total sample size, a significant association was
      observed in the small sample size subgroup (total sample size < 300), but the
      results should be interpreted with caution. In conclusion, this meta-analysis
      failed to confirm the association between the CDH1 C-160A polymorphism and risk
      of gastric cancer. Large-scale and well-designed studies are needed to confirm
      our findings. 

PMID- 25599648
TI  - Studies on the antimicrobial potential and structural characterization of fatty
      acids extracted from Sydney rock oyster Saccostrea glomerata.
AB  - BACKGROUND: The marine environment having vast resources of natural products with
      potential bioactivities. Among the marine natural products, fatty acids obtained
      from marine mollusks have broad range of biological activities including
      antimicrobial and antitumor activities. The present study aims to characterize
      the fatty acid derivatives from the Sydney rock oyster Saccostrea glomerata and
      its pharmacological activities. METHODS: S. glomerata fleshes were serially
      extracted with hexane, ethyl acetate and methanol and studied the antimicrobial
      activities against pathogenic bacteria, fungi and virus. Based on the better
      result, the ethyl acetate extract was selected and purified through silica column
      chromatography and screened the fractions for antimicrobial and antitumor
      activities. Also the best active fraction (FV) was functionally and structurally
      characterized. RESULTS: The ethyl acetate extract of S. glomerata effectively
      controlled the bacterial pathogens and formed of more than 15 mm of zone of
      inhibition and also effectively suppressed the fungal growth and inhibit the
      shrimp white spot syndrome virus (WSSV). The secondary screening results revealed
      that, the fraction (FV) had potential antimicrobial and antitumor activities. The
      FV concentration (100 MUg/ml) effectively suppressed the tumor mammary epithelial
      carcinoma cell of 14.45%. The GC-MS analysis revealed that, eleven compounds
      including N-hexadecanoic acid, L-(+)-ascorbic acid 2,6-dihexadecanoate and 6
      Octadecenoic acid were characterized. CONCLUSIONS: The fatty acid derivatives
      isolated and characterized from S. glomerata extracts had the potent
      antimicrobial and antitumor activities. This basic research can help to develop
      the antimicrobial and anticancer drugs from the nutraceuticals in future.

PMID- 25599649
TI  - Pharmacokinetics, safety and efficacy of ritonavir-boosted atazanavir (300/100 mg
      once daily) in HIV-1-infected pregnant women.
AB  - BACKGROUND: Atazanavir/ritonavir (ATV/r) is a boosted protease inhibitor
      recommended to minimize the risk of mother-to-child HIV-1 transmission (MTCT). We
      aimed to assess the pharmacokinetics, safety and efficacy of ATV/r in HIV-1
      infected pregnant women and their neonates. METHODS: A multicentre, cross
      sectional, non-interventional cohort of HIV-1-infected pregnant women receiving
      ATV/r (300/100 mg once daily) who delivered in three Paris hospitals from 2006 to
      2013 was designed. We determined antiretroviral trough plasma concentrations
      using liquid chromatography-mass spectrometry at each of the three trimesters,
      delivery and post-partum. ATV concentrations at 24 h (C24h) were interpreted by
      the 150-850 ng/ml efficacy-tolerance thresholds. Safety data and newborn HIV
      status were recorded. A mother's virological failure was defined as two
      successive measurements of plasma HIV-1 RNA>50 copies/ml within the 2 months
      before delivery. RESULTS: 103 pregnant women were included, mostly from sub
      Saharan Africa (88%). ATV C24h at each of the three trimesters and delivery
      remained similar to post-partum values. No dose adjustment was needed during
      pregnancy. The median plasma ratio of fetal/maternal ATV level was 0.19 (n=28).
      Only three patients showed two successive detectable viral loads but <400
      copies/ml. Among 82 available newborn data, 16 were born preterm. Three in utero
      deaths occurred. Tolerance was good with one case of maternal grade 3
      hyperbilirubinaemia, no cases in neonates at delivery and no clinically relevant
      adverse event. No case of MTCT was reported. CONCLUSIONS: In this population, an
      ATV/r-containing antiretroviral regimen demonstrated good pharmacokinetics,
      virological efficacy and safety. No significant impact of pregnancy on ATV C24h
      was found. No dose adjustment was required.

PMID- 25599651
TI  - Diffusion-driven and size-dependent phase changes of gallium oxide nanocrystals
      in a glassy host.
AB  - Phase transformations at the nanoscale represent a challenging field of research,
      mainly in the case of nanocrystals (NCs) in a solid host, with size-effects and
      interactions with the matrix. Here we report the study of the structural
      evolution of gamma-Ga2O3 NCs in alkali-germanosilicate glass - a technologically
      relevant system for its light emission and UV-to-visible conversion - showing an
      evolution drastically different from the expected transformation of gamma-Ga2O3
      into beta-Ga2O3. Differential scanning calorimetry registers an irreversible
      endothermic process at ~1300 K, well above the exothermic peak of gamma-Ga2O3
      nano-crystallization (~960 K) and below the melting temperature (~1620 K).
      Transmission electron microscopy and X-ray diffraction data clarify that glass
      embedded gamma-Ga2O3 NCs transform into LiGa5O8via diffusion-driven kinetics of
      Li incorporation into NCs. At the endothermic peak, beta-Ga2O3 forms from LiGa5O8
      dissociation, following a nucleation-limited kinetics promoted by size-dependent
      order-disorder change between LiGa5O8 polymorphs. As a result of the changes,
      modifications of UV-excited NC light emission are registered, with potential
      interest for applications. 

PMID- 25599650
TI  - ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination
      and organ patterning.
AB  - The ciliary kinase NEK8 plays a critical role in situs determination and cystic
      kidney disease, yet its exact function remains unknown. In this study, we
      identify ANKS6 as a target and activator of NEK8. ANKS6 requires NEK8 for
      localizing to the ciliary inversin compartment (IC) and activates NEK8 by binding
      to its kinase domain. Here we demonstrate the functional importance of this
      interaction through the analysis of two novel mouse mutations, Anks6(Streaker)
      and Nek8(Roc). Both display heterotaxy, cardiopulmonary malformations and cystic
      kidneys, a syndrome also characteristic of mutations in Invs and Nphp3, the other
      known components of the IC. The Anks6(Strkr) mutation decreases ANKS6 interaction
      with NEK8, precluding NEK8 activation. The Nek8(Roc) mutation inactivates NEK8
      kinase function while preserving ANKS6 localization to the IC. Together, these
      data reveal the crucial role of NEK8 kinase activation within the IC, promoting
      proper left-right patterning, cardiopulmonary development and renal
      morphogenesis. 

PMID- 25599652
TI  - Noninvasive depth-resolved optical measurements of the tympanic membrane and
      middle ear for differentiating otitis media.
AB  - OBJECTIVE/HYPOTHESIS: In this study, optical coherence tomography (OCT) is used
      to noninvasively and quantitatively determine tympanic membrane (TM) thickness
      and the presence and thickness of any middle-ear biofilm located behind the TM.
      These new metrics offer the potential to differentiate normal, acute, and chronic
      otitis media (OM) infections in pediatric subjects. STUDY DESIGN: Case series
      with comparison group. METHODS: The TM thickness of 34 pediatric subjects was
      acquired using a custom-built, handheld OCT system following a traditional
      otoscopic ear exam. RESULTS: Overall thickness (TM and any associated biofilm)
      was shown to be statistically different for normal, acute, and chronic infection
      groups (normal-acute and normal-chronic: P value < 0.001; acute-chronic: P value
      = 0.0016). Almost all observed scans from the chronic group had an accompanying
      biofilm structure. When the thickness of the TM and biofilm were considered
      separately in chronic OM, the chronic TM thickness correlated with the normal
      group (P value = 0.68) yet was still distinct from the acute OM group (P value <
      0.001), indicating that the TM in chronic OM returns to relatively normal
      thickness levels. CONCLUSION: Identifying these physical changes in vivo provides
      new metrics for noninvasively and quantitatively differentiating normal, acute,
      and chronic OM. This new diagnostic information has the potential to assist
      physicians to more effectively and efficiently screen, manage, and refer patients
      based on quantitative data. LEVEL OF EVIDENCE: 4.

PMID- 25599654
TI  - Does systemic steroid deficiency affect inner ear functions?
AB  - PURPOSE: Today corticosteroids are employed for the treatment of various inner
      ear disorders. In this study we have investigated probable changes in hearing
      functions resulting from a deficiency of systemic steroid secretions. MATERIALS
      AND METHODS: Twenty four healthy female rats were used in our study, allocated
      into three groups (medical adrenalectomy, medical adrenalectomy+dexamethasone, no
      treatment). Audiological evaluations were conducted at the beginning of the study
      and on days 7, 14 and 21. Blood samples were taken at the beginning and at the
      end of the study and blood corticosterone levels were determined. RESULTS: While
      there were no significant differences between the basal, 7th, 14th and 21st day
      DPOAE values of group 1, their ABR threshold values showed significant increases.
      In group 2, there were no significant differences between the basal, 7th, 14th
      and 21st day DPOAE values. ABR thresholds of group 2 showed significant increases
      on days 7 and 14 as compared to their basal values, but there were no significant
      differences between the 21st day and basal ABR threshold values. There were no
      significant differences between the basal cortisol levels of the three groups.
      The mean cortisol level of group 1 on day 21 was found to be significantly lower
      than those of groups 2 and 3. CONCLUSION: The results of the study demonstrated
      that there were no significant changes in DPOAE values with the cessation of
      cortisol secretion, while there was a progressive increase in ABR thresholds,
      which could be overcome with cortisone replacement.

PMID- 25599653
TI  - Differential reprogramming of isogenic colorectal cancer cells by distinct
      activating KRAS mutations.
AB  - Oncogenic mutations of Ras at codons 12, 13, or 61, that render the protein
      constitutively active, are found in ~ 16% of all cancer cases. Among the three
      major Ras isoforms, KRAS is the most frequently mutated isoform in cancer. Each
      Ras isoform and tumor type displays a distinct pattern of codon-specific
      mutations. In colon cancer, KRAS is typically mutated at codon 12, but a
      significant fraction of patients have mutations at codon 13. Clinical data
      suggest different outcomes and responsiveness to treatment between these two
      groups. To investigate the differential effects upon cell status associated with
      KRAS mutations we performed a quantitative analysis of the proteome and
      phosphoproteome of isogenic SW48 colon cancer cell lines in which one allele of
      the endogenous gene has been edited to harbor specific KRAS mutations (G12V,
      G12D, or G13D). Each mutation generates a distinct signature, with the most
      variability seen between G13D and the codon 12 KRAS mutants. One notable example
      of specific up-regulation in KRAS codon 12 mutant SW48 cells is provided by the
      short form of the colon cancer stem cell marker doublecortin-like Kinase 1
      (DCLK1) that can be reversed by suppression of KRAS.

PMID- 25599655
TI  - Electrodermal Response to Reward and Non-Reward Among Children With Autism.
AB  - Pervasive social difficulties among individuals with autism spectrum disorder
      (ASD) are often construed as deriving from reduced sensitivity to social stimuli.
      Behavioral and neurobiological evidence suggests that typical individuals show
      preferential processing of social (e.g., voices, faces) over nonsocial (e.g.,
      nonvocal sounds, images of objects) information, whereas individuals with ASD may
      not. This reduction in sensitivity may reflect disrupted reward processing
      [Dawson & Bernier, ], with significant developmental consequences for affected
      individuals. In this study, we explore effects of social and monetary reward on
      behavioral and electrodermal responses (EDRs) among 8- to 12-year-old boys with
      (n = 18) and without (n = 18) ASD, with attention to the potential moderating
      effects of stimulus familiarity. During a simple matching task, participants with
      and without ASD had marginally slower reactions during social vs. nonsocial
      reward, and boys with ASD had less accurate responses than controls. Compared to
      baseline, reward and non-reward conditions elicited more frequent and larger EDRs
      for participants as a whole, and both groups showed similar patterns of EDR
      change within reward blocks. However, boys with and without ASD differed in their
      EDRs to non-reward, and response amplitude was correlated with social and
      emotional functioning. These findings provide some support for altered reward
      responding in ASD at the autonomic level, and highlight the discontinuation of
      reward as an important component of reward-based learning that may play a role in
      shaping behavior and guiding specialized brain development to subserve social
      behavior and cognition across the lifespan.

PMID- 25599656
TI  - The Uncertain Role of Immunomodulator Maintenance After Cessation of Anti-Tumor
      Necrosis Factor alpha Therapy.

PMID- 25599659
TI  - Fentanyl-induced asystole in two dogs.
AB  - Fentanyl is used in small animals for perioperative analgesia during anaesthesia.
      Severe bradycardia and asystole were observed on bolus administration of a 3
      ug/kg loading dose of fentanyl in two dogs under isoflurane anaesthesia.
      Premedication with 10 ug/kg glycopyrrolate did not prevent asystole in the first
      case; and although bradycardia was treated with 5 ug/kg glycopyrrolate
      administered intravenously in the second case, the heart rate continuously
      decreased and asystole subsequently developed. Asystole in both cases was quickly
      corrected by intravenous administration of 0 . 04 mg/kg atropine and closed chest
      compressions. This case report describes asystole induced by fentanyl
      administration in isoflurane anaesthetised dogs. Atropine was more effective than
      glycopyrrolate in the treatment of fentanyl-induced asystole. 

PMID- 25599658
TI  - Sexual maturation and administration of 17beta-estradiol and testosterone induce
      complex gene expression changes in skin and increase resistance of Atlantic
      salmon to ectoparasite salmon louse.
AB  - The crustacean ectoparasitic salmon louse (Lepeophtheirus salmonis) is a major
      problem of Atlantic salmon aquaculture in the Northern hemisphere. Host-pathogen
      interactions in this system are highly complex. Resistance to the parasite
      involves variations in genetic background, nutrition, properties of skin, and
      status of the endocrine and immune systems. This study addressed the relationship
      between sex hormones and lice infection. Field observation revealed a sharp
      reduction of lice prevalence during sexual maturation with no difference between
      male and female fish. To determine if higher resistance against lice was related
      to sex hormones, post-smolt salmon were administered control feed and feeds
      containing 17beta-estradiol (20 mg/kg) and testosterone (25 mg/kg) during a 3
      week pre-challenge period. After challenge with lice, counts were reduced 2-fold
      and 1.5-fold in fish that received 17beta-estradiol and testosterone,
      respectively. Gene expression analyses were performed from skin of salmon
      collected in the field trial and from the controlled lab experiment at three time
      points (end of feeding-before challenge, 3 days post challenge (dpc) and 16 dpc)
      using oligonucleotide microarray and qPCR. Differential expression was observed
      in genes associated with diverse biological processes. Both studies revealed
      similar changes of several antibacterial acute phase proteins; of note was
      induction of cathelicidin and down-regulation of a defensin gene. Treatment with
      hormones revealed their ability to modulate T helper cell (Th)-mediated immunity
      in skin. Enhanced protection achieved by 17beta-estradiol administration might in
      part be due to the skewing of Th responses away from the prototypic anti
      parasitic Th2 immunity and towards the more effective Th1 responses. Multiple
      genes involved in wound healing, differentiation and remodelling of skin tissue
      were stimulated during maturation but suppressed with sex hormones. Such opposite
      regulation suggested that these processes were not associated with resistance to
      the parasite under the studied conditions. Both studies revealed regulation of a
      suite of genes encoding putative large mucosal proteins found exclusively in
      fish. Marked decrease of erythrocyte markers indicated reduced circulation while
      down-regulation of multiple zymogen granule membrane proteins and transporters of
      cholesterol and other compounds suggested limited availability of nutrients for
      the parasites.

PMID- 25599660
TI  - Low-dose-intensity bevacizumab with weekly irinotecan for platinum- and taxanes
      resistant epithelial ovarian cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the safety and efficacy of low
      dose-intensity bevacizumab and weekly irinotecan as salvage treatment for
      patients with platinum- and taxanes-resistant advanced epithelial ovarian cancer.
      METHODS: Fifty-two patients with platinum- and taxanes-resistant advanced
      epithelial ovarian cancer received bevacizumab 5 mg/Kg days 1 and 15; irinotecan
      60 mg/m(2) days 1, 8 and 15. The combined therapy was repeated every 28 days, up
      to six cycles. RESULTS: A total of 230 cycles of bevacizumab combined with
      irinotecan were administrated to 52 patients. Among the 52 patients, 22 patients
      achieved partial response (42.3 %); 12 patients had stable disease (23.1 %) and
      18 patients experienced disease progression (34.6 %). The median progression-free
      survival and the median overall survival were 8.0 months (95 % confidence
      interval: 6.74-9.26 months) and 13.8 months (95 % confidence interval: 11.97
      15.63 months), respectively. The most frequent grade 3-4 hematologic toxicities
      were neutropenia (11.5 %) and thrombocytopenia (3.8 %). The non-hematologic
      toxicities included grade 3 diarrhea (3.8 %) and hypertension (3.8 %). Two
      patients (3.8 %) were confirmed with deep vein thrombosis. Febrile neutropenia,
      symptomatic cardiac dysfunction and gastrointestinal perforation were not
      observed in this study. CONCLUSIONS: The combination of low-dose-intensity
      bevacizumab and weekly irinotecan was an effective and safe regimen for patients
      with platinum- and taxanes-resistant epithelial ovarian cancer.

PMID- 25599661
TI  - Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma.
AB  - PURPOSE: The American Association for the Study of Liver Diseases and the
      European Association for the Study of the Liver exclude any role of contrast
      enhanced ultrasound (CEUS) in the diagnosis of hepatocellular carcinoma (HCC)
      while the Italian Association for the Study of the Liver suggests its use for
      larger HCC. This study evaluated the accuracy of CEUS in comparison with computed
      tomography (CT) in the diagnosis of HCC and of residual of HCC after treatment.
      MATERIALS AND METHODS: We retrospectively evaluated 124 patients with 148 HCC
      nodules: 34 small (<=20 mm) and 114 large nodules (>20 mm). Ninety-three patients
      underwent treatment [one resection, 23 transcatheter arterial chemoembolisation
      (TACE), 37 radiofrequency ablation (RFA), 32 TACE/RFA combined with sorafenib].
      The diagnosis of HCC on CEUS was confirmed by the typical pattern of arterial
      enhancement and portal and/or venous phase washout. RESULTS: We performed 90 CEUS
      for the initial diagnosis of HCC in 85 patients and 107 CEUS for the diagnosis of
      residual HCC after 1-month treatment in 92 patients. Sensitivity, specificity,
      positive predictive value, negative predictive value of CEUS and CT in the
      initial diagnosis of HCC were: 63 vs 92, 100 vs 100, 100 vs 100, 9 vs 25 for
      small HCC; 77 vs 92, 100 vs 100, 100 vs 100, 13 vs 22 for large HCC. In the
      diagnosis of residual of HCC, CEUS had a sensitivity of 70 % for small nodules
      and 76 % for large nodules, with an overall specificity of 100 %. CONCLUSION:
      CEUS is useful in the initial diagnosis and in the assessment of necrosis after
      RFA and TACE of HCC nodules.

PMID- 25599662
TI  - Radiofrequency energy ablation in a child with an implanted vagus nerve
      stimulator.
AB  - An 8-year-old girl with supraventricular tachycardia and an implanted vagus nerve
      stimulator underwent radiofrequency ablation of her supraventricular tachycardia
      substrate. No known literature exists addressing the potential interaction of
      these two technologies, although there are reported cases of interaction between
      radiofrequency and other implanted stimulating devices such as pacemakers. The
      procedure was performed successfully without observed interaction, and the
      patient's family reported no significant change in frequency of seizure control. 

PMID- 25599664
TI  - Development of a surface plasmon resonance assay to measure the binding affinity
      of wild-type influenza neuraminidase and its H274Y mutant to the antiviral drug
      zanamivir.
AB  - Influenza is one of the most common infections of the upper respiratory tract.
      Antiviral drugs that are currently used to treat influenza, such as oseltamivir
      and zanamivir, are neuraminidase (NA) inhibitors. However, the virus may develop
      resistance through single-point mutations of NA. Antiviral resistance is
      currently monitored by a labelled enzymatic assay, which can be inconsistent
      because of the short half-life of the labelled product and variations in the
      assay conditions. In this paper, we describe a label-free surface plasmon
      resonance (SPR) assay for measuring the binding affinity of NA-drug interactions.
      Wild-type (WT) NA and a histidine 274 tyrosine (H274Y) mutant were expressed in
      High FiveTM (Trichoplusia ni) insect cells. A spacer molecule (1,6-hexanediamine)
      was site-specifically conjugated to the 7-hydroxyl group of zanamivir, which is
      not involved in binding to NA, and the construct was immobilized onto a SPR
      sensor Chip to obtain a final immobilization response of 431 response units.
      Binding responses obtained for WT and H274Y mutant NAs were fitted to a simple
      Langmuir 1:1 model with drift to obtain the association (ka ) and dissociation
      (kd ) rate constants. The ratio between the binding affinities for the two
      isoforms was comparable to literature values obtained using labelled enzyme
      assays. Significant potential exists for an extension of this approach to test
      for drug resistance of further NA mutants against zanamivir and other antiviral
      drugs, perhaps paving the way for a reliable SPR biosensor assay that may replace
      labelled enzymatic assays.

PMID- 25599663
TI  - Growth and origami folding of DNA on nanoparticles for high-efficiency molecular
      transport in cellular imaging and drug delivery.
AB  - A novel three-dimensional (3D) superstructure based on the growth and origami
      folding of DNA on gold nanoparticles (AuNPs) was developed. The 3D superstructure
      contains a nanoparticle core and dozens of two-dimensional DNA belts folded from
      long single-stranded DNAs grown in situ on the nanoparticle by rolling circle
      amplification (RCA). We designed two mechanisms to achieve the loading of
      molecules onto the 3D superstructures. In one mechanism, ligands bound to target
      molecules are merged into the growing DNA during the RCA process (merging
      mechanism). In the other mechanism, target molecules are intercalated into the
      double-stranded DNAs produced by origami folding (intercalating mechanism). We
      demonstrated that the as-fabricated 3D superstructures have a high molecule
      loading capacity and that they enable the high-efficiency transport of signal
      reporters and drugs for cellular imaging and drug delivery, respectively. 

PMID- 25599665
TI  - Lateralisation of aggressive displays in a tephritid fly.
AB  - Lateralisation (i.e. different functional and/or structural specialisations of
      the left and right sides of the brain) of aggression has been examined in several
      vertebrate species, while evidence for invertebrates is scarce. In this study, we
      investigated lateralisation of aggressive displays (boxing with forelegs and wing
      strikes) in the Mediterranean fruit fly, Ceratitis capitata. We attempted to
      answer the following questions: (1) do medflies show lateralisation of aggressive
      displays at the population-level; (2) are there sex differences in lateralisation
      of aggressive displays; and (3) does lateralisation of aggression enhance
      fighting success? Results showed left-biased population-level lateralisation of
      aggressive displays, with no consistent differences among sexes. In both male
      male and female-female conflicts, aggressive behaviours performed with left body
      parts led to greater fighting success than those performed with right body parts.
      As we found left-biased preferential use of body parts for both wing strikes and
      boxing, we predicted that the left foreleg/wing is quicker in exploring/striking
      than the right one. We characterised wing strike and boxing using high-speed
      videos, calculating mean velocity of aggressive displays. For both sexes,
      aggressive displays that led to success were faster than unsuccessful ones.
      However, left wing/legs were not faster than right ones while performing
      aggressive acts. Further research is needed on proximate causes allowing enhanced
      fighting success of lateralised aggressive behaviour. This is the first report
      supporting the adaptive role of lateralisation of aggressive displays in insects.

PMID- 25599667
TI  - Stranded Whole Transcriptome RNA-Seq for All RNA Types.
AB  - Stranded whole transcriptome RNA-Seq described in this unit captures quantitative
      expression data for all types of RNA including, but not limited to, miRNA
      (microRNA), piRNA (Piwi-interacting RNA), snoRNA (small nucleolar RNA), lincRNA
      (large non-coding intergenic RNA), SRP RNA (signal recognition particle RNA),
      tRNA (transfer RNA), mtRNA (mitochondrial RNA), and mRNA (messenger RNA). The
      size and nature of these types of RNA are irrelevant to the approach described
      here. Barcoded libraries for multiplexing on the Illumina platform are generated
      with this approach but it can be applied to other platforms with a few
      modifications.

PMID- 25599668
TI  - Diagnosing lysosomal storage disorders: mucopolysaccharidosis type I.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder due to
      deficiency of alpha iduronidase (IDUA). Progressive storage of dermatan and
      heparan sulfate throughout the body lead to a multiorgan presentation including
      short stature, dysostosis multiplex, corneal clouding, hearing loss, coarse
      facies, hepatosplenomegaly, and intellectual disability. Diagnosis of MPS I is
      based on IDUA enzyme analysis in leukocytes or dried blood spots (DBS) followed
      by molecular confirmation of the IDUA gene mutations in individuals with low
      enzyme activity. The advent of mass spectrometry methods for enzyme analysis in
      DBS has enabled high-throughput screening for MPS I in symptomatic individuals
      and newborn infants. The following unit provides the detailed analytical protocol
      for measurement of IDUA activity in DBS using tandem mass spectrometry.

PMID- 25599666
TI  - Statistical methods for genome-wide and sequencing association studies of complex
      traits in related samples.
AB  - Genome-wide association studies (GWAS) and sequencing studies are routinely
      conducted for the identification of genetic variants that are associated with
      complex traits. Many genetic studies for association mapping include related
      individuals. When relatives are included in an association analysis, familial
      correlations must be appropriately taken into account to ensure correct type I
      error and to increase power. This unit provides an overview of statistical
      methods that are available for GWAS and sequencing association studies of complex
      traits in samples with related individuals.

PMID- 25599670
TI  - Noninvasive prenatal testing using cell-free fetal DNA in maternal plasma.
AB  - Noninvasive prenatal testing (NIPT) represents an outstanding example of how
      novel scientific discoveries can be quickly and successfully developed into
      hugely impactful clinical diagnostic tests. Since the introduction of NIPT to
      detect trisomy 21 in late 2011, the technology has rapidly advanced to analyze
      other autosomal and sex chromosome aneuploidies, and now includes the detection
      of subchromosomal deletion and duplication events. Here we provide a brief
      overview of how noninvasive prenatal testing using next-generation sequencing is
      performed.

PMID- 25599669
TI  - Molecular cytogenetic analysis of telomere rearrangements.
AB  - Genomic imbalances involving the telomeric regions of human chromosomes, which
      contain the highest gene concentration in the genome, are proposed to have severe
      phenotypic consequences. For this reason, it is important to identify telomere
      rearrangements and assess their contribution to human pathology. This unit
      describes the structure and function of human telomeres and outlines several
      methodologies that can be employed to study these unique regions of human
      chromosomes. It is a revision of the original version of the unit published in
      2000, now including an introductory section describing advances in the discipline
      that have taken place since the original publication.

PMID- 25599671
TI  - Preparation of Cells from Formalin-Fixed, Paraffin-Embedded Tissue for Use in
      Fluorescence In Situ Hybridization (FISH) Experiments.
AB  - Numerical and structural chromosome abnormalities can be accurately detected in
      cells from archived tissues using fluorescence in situ hybridization (FISH). This
      unit describes two common approaches to performing FISH in formalin-fixed,
      paraffin-embedded tissue. The first approach utilizes 4 to 6 MUm tissue sections
      in cases for which preserving tissue morphology is necessary, and the second
      involves extraction of intact nuclei from 50-MUm tissue sections. To interpret
      FISH results using 4 to 6 MUm sections, an adequate number of nuclei must be
      evaluated to perform statistical analysis. Evaluation of 30 to 50 nuclei from the
      single-cell suspension generally gives an interpretable result.

PMID- 25599673
TI  - Factors associated with adoption of health information technology: a conceptual
      model based on a systematic review.
AB  - BACKGROUND: The Health Information Technology for Economic and Clinical Health
      Act (HITECH) allocated $19.2 billion to incentivize adoption of the electronic
      health record (EHR). Since 2009, Meaningful Use Criteria have dominated
      information technology (IT) strategy. Health care organizations have struggled to
      meet expectations and avoid penalties to reimbursements from the Center for
      Medicare and Medicaid Services (CMS). Organizational theories attempt to explain
      factors that influence organizational change, and many theories address changes
      in organizational strategy. However, due to the complexities of the health care
      industry, existing organizational theories fall short of demonstrating
      association with significant health care IT implementations. There is no
      organizational theory for health care that identifies, groups, and analyzes both
      internal and external factors of influence for large health care IT
      implementations like adoption of the EHR. OBJECTIVE: The purpose of this
      systematic review is to identify a full-spectrum of both internal organizational
      and external environmental factors associated with the adoption of health
      information technology (HIT), specifically the EHR. The result is a conceptual
      model that is commensurate with the complexity of with the health care sector.
      METHODS: We performed a systematic literature search in PubMed (restricted to
      English), EBSCO Host, and Google Scholar for both empirical studies and theory
      based writing from 1993-2013 that demonstrated association between influential
      factors and three modes of HIT: EHR, electronic medical record (EMR), and
      computerized provider order entry (CPOE). We also looked at published books on
      organizational theories. We made notes and noted trends on adoption factors.
      These factors were grouped as adoption factors associated with various versions
      of EHR adoption. RESULTS: The resulting conceptual model summarizes the diversity
      of independent variables (IVs) and dependent variables (DVs) used in articles,
      editorials, books, as well as quantitative and qualitative studies (n=83). As of
      2009, only 16.30% (815/4999) of nonfederal, acute-care hospitals had adopted a
      fully interoperable EHR. From the 83 articles reviewed in this study, 16/83 (19%)
      identified internal organizational factors and 9/83 (11%) identified external
      environmental factors associated with adoption of the EHR, EMR, or CPOE. The
      conceptual model for EHR adoption associates each variable with the work that
      identified it. CONCLUSIONS: Commonalities exist in the literature for internal
      organizational and external environmental factors associated with the adoption of
      the EHR and/or CPOE. The conceptual model for EHR adoption associates internal
      and external factors, specific to the health care industry, associated with
      adoption of the EHR. It becomes apparent that these factors have some level of
      association, but the association is not consistently calculated individually or
      in combination. To better understand effective adoption strategies, empirical
      studies should be performed from this conceptual model to quantify the positive
      or negative effect of each factor.

PMID- 25599672
TI  - Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and
      focal cortical dysplasia.
AB  - Focal malformations of cortical development, including focal cortical dysplasia
      (FCD) and hemimegalencephaly (HME), are important causes of intractable childhood
      epilepsy. Using targeted and exome sequencing on DNA from resected brain samples
      and nonbrain samples from 53 patients with FCD or HME, we identified pathogenic
      germline and mosaic mutations in multiple PI3K/AKT pathway genes in 9 patients,
      and a likely pathogenic variant in 1 additional patient. Our data confirm the
      association of DEPDC5 with sporadic FCD but also implicate this gene for the
      first time in HME. Our findings suggest that modulation of the mammalian target
      of rapamycin pathway may hold promise for malformation-associated epilepsy.

PMID- 25599676
TI  - Contemporary practice and technical aspects in coronary intervention with
      bioresorbable scaffolds: a European perspective.
AB  - AIMS: Next to patient characteristics, the lack of a standardised approach for
      bioresorbable vascular scaffold (BVS) implantation is perceived as a potential
      explanation for the heterogeneous results reported so far. To provide some
      guidance, we sought to find a consensus on the best practices for BVS
      implantation and management across a broad array of patient and lesion scenarios.
      METHODS AND RESULTS: Fourteen European centres with a high volume of BVS
      procedures combined their efforts in an informal collaboration. To get the most
      objective snapshot of different practices among the participating centres, a
      survey with 45 multiple choice questions was prepared and conducted. The results
      of the survey represented a basis for the technical advice provided in the
      document, whereas areas of controversy are highlighted. CONCLUSIONS: Consensus
      criteria for patient and lesion selection, BVS implantation and optimisation, use
      of intravascular imaging guidance, approach to multiple patient and lesion
      scenarios, and management of complications, were identified.

PMID- 25599675
TI  - Successful versus unsuccessful antegrade recanalization of single chronic
      coronary occlusion: eight-year experience and outcomes by a propensity score
      ascertainment.
AB  - AIMS: The effectiveness of revascularization of chronic total occlusion (CTO)
      remains intriguing. Thus, we sought to investigate whether a successful PCI for
      single CTO improves outcomes in a setting of stable angina and chronic occlusion
      of single coronary artery. METHODS AND RESULTS: Of 11 957 consecutive patients
      referred for nonurgent PCI between 2003 and 2010, 1110 displayed single CTO and
      were enrolled to the central CTO-registry database. The primary end-point
      included all-cause mortality, the secondary end-point a composite of safety
      outcome measure of all-cause death, nonfatal-MI, the need for urgent
      revascularization and stroke. The major adverse cardiovascular event (MACE)
      records were extracted from the national administrative database and all patients
      were linked to the long-term follow-up. Since the patient assignment was not
      random, we performed the propensity scoring to minimize selection bias; 734
      patients (66%) had a successful PCI-CTO. Compared with successful procedures,
      unsuccessful procedures had similar rates of all-cause death both in crude (HR,
      0.78; 95%CI, 0.49-1.25; P = 0.30) and adjusted analysis (HR, 0.80; 95%CI, 0.50
      1.28; P = 0.34). A similar, significant reduction in overall MACE was noted with
      successful PCI-CTO compared with unsuccessful procedure in unadjusted (HR, 0.74;
      95%CI, 0.56-0.96; P = 0.020) and adjusted calculation (HR, 0.73; 95%CI, 0.56
      0.96; P = 0.019). Patients after successful PCI-CTO as compared with failed
      recanalization less frequently underwent surgical revascularization. The benefit
      was sustained at 3 years follow-up. CONCLUSIONS: Successful PCI for single CTO
      does not improve long-term survival, nonetheless, is associated with reduced
      overall MACE and the need for surgical revascularization.

PMID- 25599677
TI  - Mechanism of glutamine inhibition of cytosolic phospholipase a2 (cPLA2 ):
      Evidence of physical interaction between glutamine-Induced mitogen-activated
      protein kinase phosphatase-1 and cPLA2.
AB  - Non-essential amino acid L-glutamine (Gln) possesses anti-inflammatory activity
      via deactivating cytosolic phospholipase A2 (cPLA2 ). We showed previously that
      Gln deactivated cPLA2 indirectly via dephosphorylating p38 mitogen-activated
      protein kinase (MAPK), the major kinase for cPLA2 phosphorylation, through
      inducing MAPK phosphatase-1 (MKP-1). In this study, we investigated the precise
      mechanism underlying Gln deactivation of cPLA2 . In lipopolysaccharide (LPS)
      treated mice, Gln injection resulted in dephosphorylation of phosphorylated cPLA2
      (p-cPLA2 ), which coincided with rapid Gln induction of MKP-1. MKP-1 small
      interfering RNA (siRNA) abrogated the ability of Gln to induce MKP-1 as well as
      the dephosphorylation of cPLA2 . Co-immunoprecipitation and in-situ proximity
      ligation assay revealed a physical interaction between MKP-1 and p-cPLA2 . In a
      murine model of allergic asthma, we also demonstrated the physical interaction
      between MKP-1 and p-cPLA2 . Furthermore, Gln suppressed various allergic asthma
      phenotypes, such as neutrophil and eosinophil recruitments into the airway,
      airway levels of T helper type 2 (Th2) cytokines [interleukin (IL)-4, IL-5 and IL
      13], airway hyperresponsiveness, mucin production and metabolites (leukotriene B4
      and platelet-activating factor) through inhibiting cPLA2 in a MKP-1-dependent
      manner. These data suggest that MKP-1 uses cPLA2 , in addition to p38, as a
      substrate, which further potentiates the anti-inflammatory action of Gln. 

PMID- 25599679
TI  - Kawasaki disease and its treatment - an update.
AB  - AIM: The aim of this review is to update the knowledge about the Kawasaki disease
      (KD) which includes the way of early detection and latest treatment plan for the
      disease. METHOD: A number of literatures were reviewed and latest information
      about the etiology, diagnosis, laboratory investigation, treatment and outcome of
      the disease was collected and depicted in the review article. RESULT: Kawasaki
      disease is a multisystem vasculitis mainly affecting medium sized blood vessels.
      It is the second most common cause of vasculitis after Henoch Scholein Purpura
      (HSP) in children. Etiology of the disease is still unknown. Auto-immunity with
      genetic influence is thought to associate with the disease. Many physicians are
      ignorant of the disease. The pediatrician must be aware of the disease and
      suspect this condition in less than 5 year old children presenting with more than
      5 days fever. the number of methods on the basis of criteria is set for the
      diagnosis of the disease. Latest treatment plan is set up for the disease which
      reduces the morbidity and mortality to a great extent. CONCLUSION: Physicians
      must have consciousness and comprehensive knowledge for the early suspicion of
      this disease. Any child presenting with fever for more than 5 days should not be
      ignored and other criteria of KD have to be evaluated by the physician. Early
      diagnosis and updated treatment are imperative for the prevention of morbidity
      and mortality for the disease.

PMID- 25599680
TI  - Generalized joint hypermobility, muscle strength and physical function in healthy
      adolescents and young adults.
AB  - BACKGROUND: Generalized Joint Hypermobility (GJH) is regarded as the main
      diagnostic criterion for Hypermobility Syndrome and is assumed to be of
      importance for the development of musculoskeletal complaints and functional
      decline. However GJH is also highly prevalent amongst healthy individuals whereas
      its consequences for physical functioning are unclear. Therefore the objective of
      the study was to determine the association of GJH with physical functioning in
      healthy adolescents and young adults. METHODS: 328 participants (mean age (sd):
      20.2 (1.8), gender (male/female): 134/194) were included. In order to establish
      the effect of GJH, subjects with symptomatic forms of GJH were excluded, as were
      subjects with other conditions that could influence physical functioning. Age,
      gender, BMI, GJH, muscle strength and physical activity level (PAL) in METS were
      collected. RESULTS: GJH was associated with reduced muscle strength for all
      muscle groups (p=<.05), controlled for age and BMI. Ranging from -0.7 to -1.0SD
      in females and -.3 to -1.3SD in males. GJH was found to be significantly
      associated with higher amounts of METS spent on cycling, ranging from +0.2 to
      +0.9SD in females (p=.002) and +0.3 to +0.9SD in males (p=.041), where lower
      amounts of METS spent on sports activities was observed, ranging from -0.4 to 
      1.2SD in females (p=.002) and -0.2 to -1.9SD in males (p=.004). CONCLUSION:
      Individuals with GJH have reduced muscle strength and tend to avoid dynamic
      activities and prefer more stable activities, like cycling. This may indicate
      that individuals with GJH adapt their behaviour to prevent musculoskeletal
      complaints and functional decline.

PMID- 25599678
TI  - Effect of combination of nerve fragments with nerve growth factor in autologous
      epineurium small gap coaptation on peripheral nerve injury repair.
AB  - The aim of this study was to explore the effect of the combination of nerve
      fragments with nerve growth factor (NGF) on the repair of peripheral nerve injury
      through autologous epineurium small gap coaptation. A total of 150 male Sprague
      Dawley rats weighing 200-250 g were divided into five groups randomly with 30
      rats per group, including the following: a control group that was subjected to
      traditional end-to-end neuroanastomosis; an autologous epineurium small gap group
      that received autologous epineurium small gap coaptation suture; a nerve
      fragments group in which nerve fragments were added to the small gap; an NGF
      group in which NGF was added to the small gap; and an NGF combined with nerve
      fragments group in which both NGF and nerve fragments were added to the small
      gap. All groups were examined at 4, 6, and 8 weeks after the operation,
      respectively; furthermore, electroneurophysiological detection and histological
      observation were performed at 8 weeks. Autonomic activities and root ulcers
      recovered sooner in rats in the NGF combined with nerve fragments group than the
      other groups. Moreover, the numbers of regenerated nerve fibers were greater and
      nerve conduction velocity was faster in the NGF combined with nerve fragments
      group than the other groups. Therefore, the combination of NGF with nerve
      fragments plays a significant role in the repair of peripheral nerve injury
      through autologous epineurium small gap coaptation. Therefore, compared with the
      other four methods, the combination of nerve fragments with NGF on the repair of
      peripheral nerve injury through autologous epineurium small gap coaptation has a
      better effect. 

PMID- 25599681
TI  - Pattern of primary vasculitis with peripheral ischemic manifestations: report of
      a case series and role of vascular surgery.
AB  - AIM OF THE WORK: The aim of the present work was to study the role of vascular
      surgery in the management of primary vasculitis patients with peripheral ischemic
      manifestations. PATIENTS AND METHODS: Ten primary vasculitis patients with
      peripheral ischemic manifestations were studied and reviewed for the diagnosis,
      clinical manifestations, investigations, treatment options and role of vascular
      surgery. The Birmingham Vasculitis Activity Score (BVAS) was recorded. RESULTS:
      Giant cell arteritis was present in one patient; granulomatosis with polyangiitis
      in 5, essential cryoglobulinemic vasculitis in 3 and 1 (child) had Henoch
      Schonlein purpura. They showed the following peripheral vascular manifestations:
      intermittent claudications, Raynauds, deep venous thrombosis and
      thrombophelebitis in 10% each; digital ulceration and trophic changes in 20%
      while acrocyanosis and dry gangrene were present in 30%. Renal involvement was
      present in 60% of patients. The mean BVAS was 11.5 +/- 6.57 at initial
      presentation. The disease activity remarkably improved over the disease course in
      all patients to be at their last visit (2.6 +/- 2.22) (p=0.002). Regarding the
      vascular surgery role in their management, in addition to their medical
      treatment, 40% required an additional surgical intervention. Two had a minor
      amputation of the toes; one performed thoracoscopic cervical sympathectomy and
      another needed tibial angioplasty. CONCLUSION: Primary vasculitis patients
      presenting with peripheral ischemic manifestations require surgical attention.
      Their management is essentially medical and individualized to the diagnosis and
      presenting symptoms. Endovascular treatment may offer a safe and less invasive
      approach in high surgical risk patients. Sympathectomy is of high therapeutic
      potential in those with severe pain and trophic changes.

PMID- 25599682
TI  - Treat to target for osteoporosis: another step forward.
AB  - Monitoring treatment effects can inform both the physician and patient whether
      the medication has achieved its anticipated targets. There are several variances
      between patients cohorts included in clinical trials and subjects managed in
      standard clinical setting. Therefore, defining a patient as a "responder" or "non
      responder" to management might not be applicable in day to day care, in
      particular in patients suffering from chronic diseases. So far, in patients
      receiving treatment for osteoporosis, there is no clear guidance on when the
      fracture risk has been reduced to an acceptable low level. As a consequence, some
      patients at low risk for fracture may have continued their treatment for longer
      periods than necessary, whereas others at high risk for fracture may have their
      treatment stopped whilst the continuation of the same medication or a change to a
      more potent therapy might be of value. In many specialties, goal-directed
      treating to target is already the standard and the time has come for goal
      directed management of osteoporosis. Adopting treat-to-target approach in
      osteoporosis has the prospective of developing the patients' care, plummeting the
      osteoporotic fractures burden, in addition to having a positive cost
      effectiveness impact. This article aims at discussing the potential utility of
      "treat-to-target" approach for osteoporotic patients management in standard
      clinical practice. It also includes a suggested algorithm for long term
      osteoporosis treatment as well as post-drug holiday management based on "treat to
      target" strategy.

PMID- 25599683
TI  - Emerging patterns in wrist osteoarthritis.
AB  - The human wrist is a composite joint which incorporates multiple smaller joints.
      The biomechanics of the wrist are dependent on its bony structure but also on the
      ligamentous constitution of its joints. This increases the complexity of the
      joint and reduces our ability to understand its anatomy, mechanics and pathology.
      Therefore, our understanding and treatment of osteoarthritis in the wrist lags
      behind that of other joints in the body such as the knee. We discuss some of the
      recent directions in the comprehension and treatment of wrist osteoarthritis. 

PMID- 25599684
TI  - Association of anti-cyclic citrullinated peptide antibodies with clinical and
      radiological disease severity in rheumatoid arthritis.
AB  - OBJECTIVE: This study assessed an association of anti-cyclic citrullinated
      peptide antibodies (ACPA) with clinical and radiological disease severity in
      patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Fifty patients
      diagnosed with RA as per 2010 revised American College of Rheumatology/ European
      League Against Rheumatism (ACR/EULAR) classification criteria were included in
      this cross-sectional study. Serum levels of ACPA, C-reactive protein (CRP) and
      rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), disease activity
      score with 28-joint counts and ESR (DAS28-ESR), patient's global assessment of
      disease activity using visual analogue scale (PtGA-VAS), modified health
      assessment questionnaire score (M-HAQ) and radiological damage in hands and feet
      (modified Larsen score) were determined. RESULTS: ACPA were positive in 48 (96%)
      and RF in 44 (88%) patients. Mean Larsen score was 19.82 +/- 17.11 and mean DAS28
      ESR 6.39 +/- 1.59. A significant correlation of ACPA levels was seen with RF
      (p=0.03) and Larsen score (p=0.02) but not with DAS28-ESR (p=0.17) and M-HAQ
      (p=0.81). A significant correlation was seen between Larsen score and disease
      duration (p<0.0001), age (p=0.04), DAS28-ESR (p=0.001) and M-HAQ (p<0.0001).
      Multivariate analysis showed that painful joint count (p=0.003), ESR (p<0.001)
      and PtGA-VAS (p=0.009) were independently associated with clinical disease
      activity severity. Disease duration (p=0.01), ACPA levels (p=0.004) and DAS28-ESR
      (p=0.03) were independently associated with radiological joint damage.
      CONCLUSION: Serum ACPA levels correlate significantly with radiological severity
      of RA but not with clinical disease severity and are independently associated
      with radiological outcome.

PMID- 25599685
TI  - Can tocilizumab decrease cartilage oligomeric matrix protein levels and disease
      activity in patients with long-standing rheumatoid arthritis?
AB  - Serum cartilage oligomeric matrix protein (COMP) level is a new marker of joint
      destruction in patients with rheumatoid arthritis (RA), and a new means of
      identifying patients with progressive joint damage. To evaluate the effect of
      tocilizumab (TCZ) on serum COMP levels, and whether there is any difference in
      this effect between patients failing on anti-TNF treatment and those failing on
      disease-modifying anti-rheumatic drugs (DMARDs). Fifty-one patients with long
      standing RA (42 F, 9 M; mean age 62 +/- 14 years; disease duration 4.5 +/- 1.2
      years) unresponsive to DMARDs and anti-TNF drugs were treated with TCZ 8
      mg/kg/month. Serum COMP levels were measured by means of an ELISA at baseline and
      after six months of TCZ treatment; the patents' DAS28 scores and levels of RF
      (IgM, IgG, IgA), anti-CCP autoantibodies, ESR, CRP and IL-6 were evaluated at the
      same times. After six months of TCZ treatment, there was a significant decrease
      from baseline in ESR (46.1 [28.7-68.9] vs 34.3 [4.1- 58.8] mm/h, P <0.0001), CRP
      (2.2 [0.8-4.4] vs 1.3 [0.7-3.8] mg/dL, P <0.0001), TNF-alpha (21.3 [7.6-29.8] vs
      17.4 [3.4-28.6] pg/mL, P=0.0408), IL-6 (6.9 [3.5-9.6] vs 3.4 [3.0-9.6] pg/mL,
      p<0.0001); anti-CCP (55.1 [30.2-273.0] vs 54.7 [30.1- 269.8] IU/mL, P=0.9683), RF
      IgM (142.0 [48.0-260.0] vs 138.0 [42.0-243.0] IU/mL, P=0.4828), RF-IgA (81.0 [20
      140] vs 108.0 [20-175] U/mL, P=0.0003), and RF-IgG (65.2 [30-158] vs 58.3 [38.0
      158.0] U/mL, P=0.2671). There was also a significant decrease in DAS28 scores
      (4.3 [3.2-5.9] vs 3.7 [2.3-5.4], P <0.0001), and a non-significant decrease in
      serum COMP levels (0.95 [0.04-2.90] vs 0.98 [0.05-2.36] MUg/mL; P = 0.9856). A
      decrease in serum COMP levels was observed in the patients failing on anti-TNF
      treatment or anti-DMARDs without any difference. TCZ therapy in patients with
      long-standing RA is associated with a significant decrease in ESR, CRP, IL-6, TNF
      and DAS28 values, and a decrease in serum COMP levels, particularly in patients
      failing on previous anti-TNF therapy. These findings suggest that TCZ has an
      effect on cartilage joint destruction after only six months of treatment.

PMID- 25599686
TI  - Diagnosis of systemic lupus erythematosus in an unusual presentation: what a
      primary care physician should know.
AB  - Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease affecting
      millions of people worldwide. It can affect any organ systems of the body.
      However, all systems may not be involved initially rather than they may be
      affected gradually, sometimes over years. Diagnosis depends on characteristic
      clinical features and laboratory test results. Some features such as skin rash,
      joint symptoms and oral ulcers are common in SLE. But initial presentation of
      many patients is unusual because either they do not have these common features of
      the disease or the presentation mimics other illnesses. As a result, delayed
      diagnosis and misdiagnosis are common. Therefore, high index of initial suspicion
      of SLE is critical. In clinical practice, SLE should be suspected in any patient
      presenting with an unexplained disease process involving two or more organ
      systems. To make a diagnosis in an unusual presentation, thorough clinical
      evaluation with details history of both present and past illnesses as well as
      laboratory tests for SLE should be performed. Usually primary-care physicians
      first evaluate SLE patients; but there is no single article, where all the
      information on when to suspect SLE in an unusual presentation, is available in an
      integrated form. In this article, a list of conditions, when SLE should be
      suspected in an unusual presentation, has been given and some relatively common
      areas with diagnostic challenges of SLE have been briefly described. To prepare
      this manuscript, most articles have been identified through 'Pubmed' search using
      keywords-atypical/ unusual presentation of SLE, case reports on SLE,
      gastrointestinal manifestations of SLE, neuropsychiatric SLE, diagnostic
      challenges with SLE, etc. Selected most articles are from currently medline
      indexed journals. 

PMID- 25599687
TI  - Childhood bullying and healthcare adherence in adulthood.
AB  - BACKGROUND: The relationship between childhood bullying and healthcare adherence
      in adulthood has been rarely studied, but one published study suggests that being
      bullied in childhood is related to lower healthcare adherence among adolescents.
      This previous study examined few adherence variables and was limited to youths.
      AIMS: In this study, we assessed five variables for childhood bullying as related
      to seven measures of healthcare adherence among a cohort of adult primary care
      outpatients. METHOD: Using a cross-sectional, self-report survey methodology in a
      sample of 263 consecutive internal medicine outpatients, we examined five aspects
      of bullying and seven aspects of adherence with general healthcare. RESULTS:
      Being a victim of bullying, type of bullying (emotional, physical), number of
      years bullied and number of bullies each evidenced no statistical relationships
      with healthcare adherence. However, being a bully demonstrated several
      statistical relationships with healthcare adherence, indicating less adherence to
      instructions provided by healthcare professionals. CONCLUSIONS: Despite all of
      the deleterious psychological and physical effects of being bullied in childhood,
      there was no evidence that non-adherence with healthcare in adulthood is one of
      them. In contrast, bullies evidenced several areas of reduced healthcare
      adherence.

PMID- 25599688
TI  - Variation in the pharmaceutical costs of New Zealand general practices: a
      national database linkage study.
AB  - BACKGROUND: Variation in prescription costs between general practices and within
      practices over time is poorly understood. METHODS: From New Zealand's national
      health data collections, we extracted dispensed medicines data for 1045 general
      practices in 2011 and 917 practices continuously existing 2008-11. Using indirect
      standardization to account for patient demographics and morbidity, a standardized
      prescribing cost ratio (SPR: the ratio of actual : expected prescription costs)
      was calculated for each practice in each year. Case studies of three outlier
      clinics explored reasons for their status. RESULTS: SPRs ranged from 0.53 to 2.28
      (median = 0.98). Of 469 practices with higher than expected costs (SPR > 1.0) in
      2011, 204 (43.5%) had a single medicine or therapeutic drug class accounting for
      >15% of total costs. Case studies contrasted practices with overall
      pharmaceutical expenditure influenced strongly by a few patients needing high
      cost medicines, more patients using medicines in one high-cost therapeutic drug
      class (antiretrovirals), and high medicine use across all therapeutic drug
      classes. CONCLUSIONS: Routine data collections can measure inter-practice
      variation in prescription costs, adjusted for differences in the demography and
      morbidity profile of each practice's patients. Small groups of patients using
      high-cost medicines influence general practices' expenditure on pharmaceuticals.

PMID- 25599689
TI  - US health secretary calls on Republicans to move on from Obamacare debate.

PMID- 25599690
TI  - Effectiveness of a combined strategy to improve therapeutic compliance and degree
      of control among patients with hypercholesterolaemia: a randomised clinical
      trial.
AB  - BACKGROUND: In subjects with hypercholesterolaemia, cholesterol values remain
      above guideline levels. One of the limiting factors to the achievement of goals
      in such patients is therapeutic non-adherence. The aim of this study is to assess
      the effectiveness of an intervention designed to improve control of
      hypercholesterolaemic patients, consisting of a combined strategy that would
      include the delivery of printed information, treatment-compliance check cards and
      the dispatch of text messages as complementary measures in support of the
      intervention at the general practitioner's practice. METHODS/DESIGN: A
      randomised, parallel-group clinical trial will be conducted at the family
      medicine outpatient facilities of eight health centres in three of Spain's
      Autonomous Regions (Comunidades Autonomas), covering a total of 358 subjects aged
      18 years or over with diagnosis of hypercholesterolaemia. Patients in the
      intervention group will be supplied with printed material with information on the
      disease and its management, mobile-telephone text messages with guideline
      summaries, reminders of forthcoming appointments and/or arrangements for making
      new appointments in the event of non-attendance, and self-report cards to check
      compliance with recommendations. Both groups -intervention and control- will
      receive routine recommendations from their physicians in accordance with current
      European clinical practice guidelines for hypercholesterolaemia and
      cardiovascular risk management. As regards the measurements to be made, the main
      variable is the proportion of subjects who attain the low density lipoprotein
      cholesterol levels set as a target across a follow-up period of 24 months. The
      secondary variables are as follows: adherence to recommendations on lifestyle and
      adherence to drug treatment; variation in lipid profiles and cardiovascular risk
      levels; appearance of cardiovascular events; physical activity; food consumption;
      smoking habit; anthropometric measures; blood pressure; health problems; use of
      hypolipidaemic agents; socio-demographic data; beliefs and expectations about
      preventive recommendations; and degree of satisfaction with the combined
      strategy. DISCUSSION: Should this intervention prove effective, a recommendation
      could be issued on the application of this combined strategy to subjects with
      hypercholesterolaemia. It is a simple, relatively inexpensive intervention. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02314663.

PMID- 25599692
TI  - Commentary: 'Smoking, caning and delinquency in a secondary modern school': a
      pioneer study by JW Palmer.

PMID- 25599693
TI  - Smoking, caning, and delinquency in a secondary modern school.
AB  - This study was designed in 1962 to investigate the reformative effect of a
      particular punishment (caning) for a particular offence (smoking by schoolboys).
      In 1964, in the course of a larger study of juvenile offences, delinquency
      records were obtained from the police, and the relationship between smoking and
      delinquency is also discussed in this paper. 

PMID- 25599694
TI  - Commentary: punishment and palmer.

PMID- 25599691
TI  - N-methyl-D-aspartate receptors mediate activity-dependent down-regulation of
      potassium channel genes during the expression of homeostatic intrinsic
      plasticity.
AB  - BACKGROUND: Homeostatic intrinsic plasticity encompasses the mechanisms by which
      neurons stabilize their excitability in response to prolonged and destabilizing
      changes in global activity. However, the milieu of molecular players responsible
      for these regulatory mechanisms is largely unknown. RESULTS: Using whole-cell
      patch clamp recording and unbiased gene expression profiling in rat dissociated
      hippocampal neurons cultured at high density, we demonstrate here that chronic
      activity blockade induced by the sodium channel blocker tetrodotoxin leads to a
      homeostatic increase in action potential firing and down-regulation of potassium
      channel genes. In addition, chronic activity blockade reduces total potassium
      current, as well as protein expression and current of voltage-gated Kv1 and Kv7
      potassium channels, which are critical regulators of action potential firing.
      Importantly, inhibition of N-Methyl-D-Aspartate receptors alone mimics the
      effects of tetrodotoxin, including the elevation in firing frequency and
      reduction of potassium channel gene expression and current driven by activity
      blockade, whereas inhibition of L-type voltage-gated calcium channels has no
      effect. CONCLUSIONS: Collectively, our data suggest that homeostatic intrinsic
      plasticity induced by chronic activity blockade is accomplished in part by
      decreased calcium influx through N-Methyl-D-Aspartate receptors and subsequent
      transcriptional down-regulation of potassium channel genes.

PMID- 25599695
TI  - Effect of a mobile phone intervention on quitting smoking in a young adult
      population of smokers: randomized controlled trial study protocol.
AB  - BACKGROUND: Tobacco use remains the number one cause of preventable chronic
      disease and death in developed countries worldwide. In North America, smoking
      rates are highest among young adults. Despite that the majority of young adult
      smokers indicate wanting to quit, smoking rates among this age demographic have
      yet to decline. Helping young adults quit smoking continues to be a public health
      priority. Digital mobile technology presents a promising medium for reaching this
      population with smoking cessation interventions, especially because young adults
      are the heaviest users of this technology. OBJECTIVE: The primary aim of this
      trial is to determine the effectiveness of an evidence-informed mobile phone app
      for smoking cessation, Crush the Crave, on reducing smoking prevalence among
      young adult smokers. METHODS: A parallel randomized controlled trial (RCT) with
      two arms will be conducted in Canada to evaluate Crush the Crave. In total, 1354
      young adult smokers (19 to 29 years old) will be randomized to receive the
      evidence-informed mobile phone app, Crush the Crave, or an evidence-based self
      help guide known as "On the Road to Quitting" (control) for a period of 6 months.
      The primary outcome measure is a 30-day point prevalence of abstinence at the 6
      month follow-up. Secondary outcomes include a 7-day point prevalence of
      abstinence, number of quit attempts, reduction in consumption of cigarettes, self
      efficacy, satisfaction, app utilization metrics, and use of smoking cessation
      services. A cost-effectiveness analysis is included. RESULTS: This trial is
      currently open for recruitment. The anticipated completion date for the study is
      April 2016. CONCLUSIONS: This randomized controlled trial will provide the
      evidence to move forward on decision making regarding the inclusion of technology
      based mobile phone interventions as part of existing smoking cessation efforts
      made by health care providers. Evidence from the trial will also inform the
      development of future apps, provide a deeper understanding of the factors that
      drive change in smoking behavior using an app, and improve the design of
      cessation apps. This trial is among the first to assess the effect of a
      comprehensive and evidence-informed mHealth smoking cessation app on a large
      sample of young adult smokers. Strengths of the trial include the high-quality
      research design and in-depth assessment of the implementation of the
      intervention. If effective, the trial has the potential to demonstrate that
      including mHealth technology as a population-based intervention strategy can cost
      effectively reach a greater proportion of the population and help young adult
      smokers to quit. TRIAL REGISTRATION: ClinicalTrials.gov NCT01983150;
      http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at
      http://www.webcitation.org/6VGyc0W0i).

PMID- 25599698
TI  - Frequency domain optical coherence tomography to assess non-ostial left main
      coronary artery.
AB  - AIMS: The aim of this study was to assess the feasibility of unprotected non
      ostial left main (LM) imaging by frequency domain optical coherence tomography
      (FD-OCT). METHODS AND RESULTS: We conducted a retrospective analysis of OCT
      studies performed to image lesions located in the non-ostial LM. OCT studies were
      analysed off-line to detect the number of artefact frames in the different
      LM/bifurcation segments. OCT cross-sectional images were used to assess area
      measures. OCT longitudinal reconstructions were used to obtain the LM length.
      Standard quantitative coronary angiography (QCA) was used as the reference
      methodology. A total of 54 patients with non-ostial LM disease entered the study.
      The mean number of LM artefact frames was 8+/-10, corresponding to 19% of the
      total number of LM frames analysed. The percentages of artefact frames differed
      significantly according to the segment analysed: 43.3% proximal LM, 11.4% mid LM
      and 2.1% distal LM, 2.0% ostial left anterior descending artery and 0% ostial
      left circumflex artery (p<0.0001). All LM OCT measurements were significantly
      correlated with QCA measurements. CONCLUSIONS: The results of the present study
      show that FD-OCT assessment of non-ostial LM disease is feasible and may provide
      high-quality imaging. OCT assessment of distal LM is more efficient than that of
      the proximal LM segment.

PMID- 25599696
TI  - Metal ion-assisted self-assembly of complexes for controlled and sustained
      release of minocycline for biomedical applications.
AB  - This study reports the development of novel drug delivery complexes self
      assembled by divalent metal ion-assisted coacervation for controlled and
      sustained release of a hydrophilic small drug molecule minocycline hydrochloride
      (MH). MH is a multifaceted agent that has demonstrated therapeutic effects in
      infection, inflammation, tumor, as well as cardiovascular, renal, and
      neurological disorders due to its anti-microbial, anti-inflammatory, and
      cytoprotective properties. However, the inability to translate the high doses
      used in experimental animals to tolerable doses in human patients limits its
      clinical application. Localized delivery can potentially expose the diseased
      tissue to high concentrations of MH that systemic delivery cannot achieve, while
      minimizing the side effects from systemic exposure. The strong metal ion binding
      assisted interaction enabled high drug entrapment and loading efficiency, and
      stable long term release for more than 71 d. Released MH demonstrated potent anti
      biofilm, anti-inflammatory, and neuroprotective activities. Furthermore, MH
      release from the complexes is pH-sensitive as the chelation between minocycline
      and metal ions decreases with pH, allowing 'smart' drug release in response to
      the severity of pathology-induced tissue acidosis. This novel metal ion binding
      mediated drug delivery mechanism can potentially be applied to other drugs that
      have high binding affinity for metal ions and may lead to the development of new
      delivery systems for a variety of drugs. 

PMID- 25599697
TI  - OWLing Clinical Data Repositories With the Ontology Web Language.
AB  - BACKGROUND: The health sciences are based upon information. Clinical information
      is usually stored and managed by physicians with precarious tools, such as
      spreadsheets. The biomedical domain is more complex than other domains that have
      adopted information and communication technologies as pervasive business tools.
      Moreover, medicine continuously changes its corpus of knowledge because of new
      discoveries and the rearrangements in the relationships among concepts. This
      scenario makes it especially difficult to offer good tools to answer the
      professional needs of researchers and constitutes a barrier that needs innovation
      to discover useful solutions. OBJECTIVE: The objective was to design and
      implement a framework for the development of clinical data repositories, capable
      of facing the continuous change in the biomedicine domain and minimizing the
      technical knowledge required from final users. METHODS: We combined knowledge
      management tools and methodologies with relational technology. We present an
      ontology-based approach that is flexible and efficient for dealing with
      complexity and change, integrated with a solid relational storage and a Web
      graphical user interface. RESULTS: Onto Clinical Research Forms (OntoCRF) is a
      framework for the definition, modeling, and instantiation of data repositories.
      It does not need any database design or programming. All required information to
      define a new project is explicitly stated in ontologies. Moreover, the user
      interface is built automatically on the fly as Web pages, whereas data are stored
      in a generic repository. This allows for immediate deployment and population of
      the database as well as instant online availability of any modification.
      CONCLUSIONS: OntoCRF is a complete framework to build data repositories with a
      solid relational storage. Driven by ontologies, OntoCRF is more flexible and
      efficient to deal with complexity and change than traditional systems and does
      not require very skilled technical people facilitating the engineering of
      clinical software systems.

PMID- 25599699
TI  - Everolimus-eluting stent implantation versus repeat paclitaxel-coated balloon
      angioplasty for recurrent in-stent restenosis lesion caused by paclitaxel-coated
      balloon failure.
AB  - AIMS: Although paclitaxel-coated balloon (PCB) angioplasty has been reported to
      be effective for in-stent restenosis (ISR) lesions, the optimal treatment for
      recurrent ISR lesions caused by PCB failure remains unclear. This study compared
      clinical and angiographic outcomes after everolimus-eluting stent (EES)
      implantation and repeat PCB angioplasty for PCB failure. METHODS AND RESULTS:
      From November 2008 to October 2011, we performed PCB angioplasty for 599 ISR
      lesions, of which 93 recurrent ISR lesions underwent EES implantation (53
      lesions, 52 patients) or repeat PCB angioplasty (40 lesions, 37 patients). The
      choice of treatment strategy was decided at the operatorOs discretion.
      Angiographic outcomes were evaluated by follow-up angiography at six to eight
      months after procedure. The baseline characteristics were similar between the two
      groups. At follow-up angiography (93.5% of all lesions), minimum lumen diameter
      was significantly larger and the binary restenosis rate was significantly lower
      after EES implantation than after repeat PCB angioplasty (2.08+/-0.79 mm vs.
      1.45+/-0.68 mm, p<0.001; 20.0% vs. 54.1%, p=0.001; respectively), whereas late
      lumen loss was not different between the two groups (0.49+/-0.62 mm vs. 0.59+/
      0.74 mm, p=0.47). At two years, the incidences of both target lesion
      revascularisation (TLR) and clinically driven TLR were significantly lower after
      EES implantation than after repeat PCB angioplasty (17.9% vs. 57.5%, p=0.001;
      5.9% vs. 18.1%, p=0.01; respectively). CONCLUSIONS: EES implantation was more
      effective for PCB failure in preventing subsequent TLR than repeat PCB
      angioplasty because of better angiographic results.

PMID- 25599700
TI  - Impact of chronic kidney disease on the outcomes of transcatheter aortic valve
      implantation: results from the FRANCE 2 registry.
AB  - AIMS: The aim of this study was to assess the influence of chronic kidney disease
      (CKD) classification on clinical outcomes in patients undergoing transcatheter
      aortic valve implantation (TAVI). METHODS AND RESULTS: Data of 2,929 consecutive
      patients undergoing TAVI in the FRANCE 2 registry were analysed. Patients were
      divided into five groups: CKD 1+2, 3a, 3b, 4, and 5. Both 30-day and one-year
      mortality rates were significantly increased and positively correlated with CKD
      severity in all groups. After adjusting for significant influential confounders
      in a Cox regression multivariate model, CKD 4 and 5 were associated with
      increased risk of both 30-day mortality and one-year mortality when compared with
      CKD 1+2 as the reference. This higher mortality was predominantly driven by renal
      failure and infection in patients with CKD 4 and 5, respectively. Procedural
      success rate in CKD 5 was significantly lower than that in other groups. All CKD
      patients trended towards a higher incidence of acute kidney injury (AKI), in
      parallel with the degree of CKD severity. CONCLUSIONS: Classification of CKD
      stages before TAVI allows risk stratification for 30-day and one-year clinical
      outcomes. CKD 3b, 4 and 5 correlate with poor outcome and are considered a
      significant risk for TAVI.

PMID- 25599701
TI  - Clinical results with the 31 mm CoreValvea in large aortic annuli: the importance
      of implantation technique.
AB  - AIMS: The CoreValve Revalving System (CRS) (Medtronic Inc., Minneapolis, MN, USA)
      is currently available in four sizes: 23 mm, 26 mm, 29 mm and 31 mm. Aim of our
      study was to assess the acute clinical results after implantation of a 31 mm CRS.
      METHODS AND RESULTS: We assessed device safety, procedural success and 30-day
      outcomes of 76 consecutive patients who underwent transcatheter aortic valve
      implantation (TAVI) from January 2012 to September 2013, for severe aortic valve
      disease. The device sizes used were 26 mm in 21 (28%), 29 mm in 20 (26%) and 31
      mm in 35 (46%) patients. Patients who received the 31 mm CRS were significantly
      younger, predominantly male, with higher STS scores and lower left ventricular
      ejection fraction. Device success was obtained in 70 cases (92%) in the overall
      population, without significant differences among groups. Procedural, fluoroscopy
      and revalving time and procedural outcomes did not differ. A significant
      reduction in transaortic gradient was obtained in all groups. We observed a low
      incidence of paraprosthetic leak in the 31 mm group. Permanent pacemaker
      implantation, bleeding, vascular and renal complications were similar among
      groups. Time of hospitalisation in CRS 31 mm patients did not differ from the
      other groups and 30-day outcomes were comparable. CONCLUSIONS: The 31 mm CRS can
      be safely implanted in patients with complex aortic valve disease, large annuli
      and dilated left ventricles.

PMID- 25599702
TI  - How should I treat a patient with severe mitral regurgitation and acute
      decompensated heart failure?

PMID- 25599703
TI  - Important knowledge for parents of children with heart disease: parent, nurse,
      and physician views.
AB  - OBJECTIVES: Parental understanding of their children's heart disease is
      inadequate, which may contribute to poor health outcomes. The purpose of this
      study was to determine what parental knowledge is important in the care of
      children with heart disease from the perspective of parents, nurses, and
      physicians. METHODS: Focus groups were formed with parents of children with
      single ventricle congenital heart disease (CHD), biventricular CHD, and heart
      transplantation, and with nurses and physicians who provide care for these
      children. A nominal group technique was used to identify and prioritise important
      parental knowledge items and themes. The voting data for each theme were reported
      by participant type--parent, nurse, and physician--and patient diagnosis--single
      ventricle CHD, biventricular CHD, and heart transplantation. RESULTS: The
      following three themes were identified as important by all groups: recognition of
      and response to clinical deterioration, medications, and prognosis and plan.
      Additional themes that were unique to specific groups included the following:
      medical team members and interactions (parents), tests and labs (parents),
      neurodevelopmental outcomes and interventions (physicians), lifelong disease
      requiring lifelong follow-up (physicians and nurses), and diagnosis, physiology,
      and interventions (single ventricle and biventricular CHD). CONCLUSIONS: Parents,
      nurses, and physicians have both common and unique views regarding what parents
      should know to effectively care for their children with single ventricle CHD,
      biventricular CHD, or heart transplantation. Specific targeted parental education
      that incorporates these findings should be provided to each group. Further
      development of questionnaires regarding parental knowledge with appropriate
      content validity is warranted.

PMID- 25599704
TI  - Square-edge intraocular lenses and epithelial lens cell proliferation:
      implications on posterior capsule opacification in an in vitro model.
AB  - BACKGROUND: To evaluate lens epithelial cell (LEC) proliferation with two
      different designs (one-piece or three-piece) of hydrophobic acrylic IOLs with 360
      degrees  square optic edge using an in vitro culture model of posterior capsule
      opacification (PCO). METHODS: This experimental study was conducted at the
      Department of NEUROFARBA, Section of Pharmacology, University of Florence, Italy.
      Human LECs were seeded and cultured in transwell cell culture inserts coated with
      a type-IV collagen membrane on which an IOL (one-piece Tecnis-1 or three-piece
      AR40E, Abbott Medical Optics Inc.) had been previously placed. As control, cells
      were plated on the insert membrane without an IOL. At day six (cells confluent in
      controls) IOLs were removed and cell counting, viability and cell density under
      and outside the IOLs were evaluated. RESULTS: No statistically significant
      difference in the number of cells (p>0.05) between inserts with the one-piece and
      three-piece IOLs was found. Cell density in the area under each IOL was
      significantly lower than in the area outside of it (p<0.05), or in the control
      insert. (p<0.05). Cell density under the single-piece IOL was not significantly
      different from that under the three-piece IOL (p>0.05). CONCLUSIONS: A 360
      degrees  sharp-edge played a crucial role in avoiding LEC migration under the IOL
      and preventing the formation of PCO after cataract surgery. Long term clinical
      evaluation is necessary to estimate functional results.

PMID- 25599705
TI  - Workshop report: Can an understanding of the mechanisms underlying age-related
      loss of muscle mass and function guide exercise and other intervention
      strategies?
AB  - An international workshop was hosted by the University of Liverpool on 15-16 July
      2011 to address at a basic level what is known about the fundamental mechanisms
      by which skeletal muscle mass and function are lost during aging and to examine
      the nature of interventions that might prevent these mechanistic changes. Of
      particular importance was to attempt to evaluate how different forms of exercise
      (or muscle contractile activity) influence these processes and how these effects
      can be best optimized to prevent or delay age-related loss of muscle function.
      The program took the form of a two-day meeting, comprising a series of invited
      talks and breakout sessions designed to identify key gaps in current knowledge
      and potential future research questions. The aims of this Workshop were two-fold:
      1. To identify the current state-of-the-art in the understanding of the
      mechanisms that contribute to loss of skeletal muscle mass and function that
      occurs with aging and to address at a mechanistic level how, and to what extent,
      exercise and/or other interventions might prevent these changes. 2. To identify
      specific areas of research where information is sparse but which are likely to
      yield data that will impact on future strategies to manipulate age-related loss
      of muscle mass and function in older people. The areas discussed in detail were
      loss of functional motor units, reduced muscle stem cell activity, age-related
      changes in transcriptional responses of muscle to exercise and nutrition, age
      related changes in protein homeostasis, mitochondrial function, altered cross
      talk between muscle with immune cells and how the developments in basic science
      to understand mechanisms underlying age-related loss of muscle mass and function
      can be translated. Following each session three key areas where further studies
      are needed were identified. 

PMID- 25599706
TI  - Computed tomography criteria for discrimination of adrenal adenomas and
      adrenocortical carcinomas: analysis of the German ACC registry.
AB  - OBJECTIVE: Thresholds of 2-20 hounsfield units (HU) in unenhanced computed
      tomography (CT) are suggested to discriminate benign adrenal tumors (BATs) from
      malignant adrenal tumors. However, these studies included only low numbers of
      adrenocortical carcinomas (ACCs). This study defines a HU threshold by inclusion
      of a large cohort of ACCs. DESIGN: Retrospective, blinded, comparative analysis
      of CT scans from 51 patients with ACCs (30 females, median age 49 years) and 25
      patients with BATs (12 females, median age 64 years) diagnosed during the period
      of 2005-2010 was performed. METHODS: Tumor density was evaluated in unenhanced CT
      by two blinded investigators. RESULTS: Median tumor size was 9 cm (range 2.0-20)
      for ACCs vs 4 cm (2.0-7.5) for BATs (P<0.0001). In ACCs, the median unenhanced HU
      value was 34 (range 14-74) in comparison with 5 (-13 to 40) in BATs (P<0.0001).
      ROC analysis revealed a HU of 21 as threshold with the best diagnostic accuracy
      (sensitivity 96%, specificity 80%, and AUC 0.89). However, two ACCs that were 5
      and 6 cm in size would have been missed. Setting the threshold to 13.9 allowed
      for 100% sensitivity, but a lower specificity of 68%. CONCLUSIONS: This first
      large study on ACCs confirmed that the vast majority of ACCs have unenhanced HU
      >21. However, to avoid misdiagnosing an ACC as benign, a threshold of 13 should
      be used.

PMID- 25599708
TI  - Circulating acylghrelin levels are suppressed by insulin and increase in response
      to hypoglycemia in healthy adult volunteers.
AB  - OBJECTIVE: Ghrelin has glucoregulatory and orexigenic actions, but its role in
      acute hypoglycemia remains uncertain. We aimed to investigate circulating levels
      of acylghrelin (AG) and unacylated ghrelin (UAG) in response to hyperinsulinemia
      and to hypoglycemia. DESIGN: A randomized, single-blind, placebo-controlled
      crossover study including 3 study days was performed at a university hospital
      clinical research center. METHODS: Nine healthy men completed 3 study days: i)
      saline control (CTR), ii) hyperinsulinemic euglycemia (HE) (bolus insulin 0.1
      IE/kg i.v. and glucose 20% i.v. for 105 min, plasma glucose ~5 mmol/l), and iii)
      hyperinsulinemic hypoglycemia (HH) (bolus insulin 0.1 IE/kg i.v.). RESULTS: HH
      and HE suppressed AG concentrations at t=45-60 min as compared with CTR (P<0.05).
      At t=90 min, a rebound increase in AG was observed in response to HH as compared
      with both HE and CTR (P<0.05). UAG also decreased during HH and HE at t=45 min
      (P<0.05), whereas the AG-to-UAG ratio remained unaffected. CONCLUSIONS: This
      study demonstrates that AG and UAG are directly suppressed by hyperinsulinemia
      and that AG concentrations increase after a latency of ~1 h in response to
      hypoglycemia, suggesting a potential counterregulatory role of AG.

PMID- 25599707
TI  - Failure to achieve disease control in acromegaly: cause analysis by a registry
      based survey.
AB  - CONTEXT: Disease control is a prime target in acromegaly treatment. This should
      be achievable in the vast majority of patients by available treatment options.
      For unknown reasons, however, a significant number of patients do not achieve
      disease control. OBJECTIVE: To investigate reasons for failure to achieve disease
      control in long-standing acromegaly. DESIGN AND METHODS: Survey based on the
      German Acromegaly Registry database (1755 patients in 57 centres). Questionnaires
      were sent to 47 centres treating 178 patients with elevated disease markers (IGF1
      and GH) at the last documented database visit out of 1528 patients with a
      diagnosis dated back >=2 years. Thirty-three centres returned anonymised
      information for 120 patients (recall rate 67.4%). RESULTS: Median age of the 120
      patients (58 females) was 57 years (range 17-84). Ninety-four patients had at
      least one operation, 29 had received radiotherapy and 71 had been previously
      treated medically. Comorbidities were reported in 67 patients. In 61 patients,
      disease activity had been controlled since the last documented database visit,
      while 59 patients still had biochemically active disease. Reasons were patients'
      denial to escalate therapy (23.3%), non-compliance (20.6%), fluctuating insulin
      like growth factor 1 (IGF-1) and growth hormone (GH) levels with normal values at
      previous visits (23.3%) and modifications in pharmacotherapy (15.1%). Therapy
      resistance (9.6%), drug side effects (4.1%) and economic considerations (4.1%)
      were rare reasons. CONCLUSIONS: Main reasons for long-standing active acromegaly
      were patients' lack of motivation to agree to therapeutic recommendations and non
      compliance with medical therapy. Development of patient education programmes
      could improve long-term control and thus prognosis of acromegalic patients.

PMID- 25599709
TI  - Therapy of endocrine disease: outcomes in patients with Cushing's disease
      undergoing transsphenoidal surgery: systematic review assessing criteria used to
      define remission and recurrence.
AB  - OBJECTIVE: A number of factors can influence the reported outcomes of
      transsphenoidal surgery (TSS) for Cushing's disease - including different
      remission and recurrence criteria, for which there is no consensus. Therefore, a
      comparative analysis of the best treatment options and patient management
      strategies is difficult. In this review, we investigated the clinical outcomes of
      initial TSS in patients with Cushing's disease based on definitions of and
      assessments for remission and recurrence. METHODS: We systematically searched
      PubMed and identified 44 studies with clear definitions of remission and
      recurrence. When data were available, additional analyses by time of remission,
      tumor size, duration of follow-up, surgical experience, year of study publication
      and adverse events related to surgery were performed. RESULTS: Data from a total
      of 6400 patients who received microscopic TSS were extracted and analyzed. A
      variety of definitions of remission and recurrence of Cushing's disease after
      initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%;
      median, 77.9%) and recurrence (0-47.4%; median, 11.5%). Better remission and
      recurrence outcomes were achieved for microadenomas vs macroadenomas; however, no
      correlations were found with other parameters, other than improved safety with
      longer surgical experience. CONCLUSIONS: The variety of methodologies used in
      clinical evaluation of TSS for Cushing's disease strongly support the call for
      standardization and optimization of studies to inform clinical practice and
      maximize patient outcomes. Clinically significant rates of failure of initial TSS
      highlight the need for effective second-line treatments.

PMID- 25599710
TI  - Chronic lymphocytic thyroiditis: could it be influenced by a petrochemical
      complex? Data from a cytological study in South-Eastern Sicily.
AB  - INTRODUCTION: In genetically predisposed individuals, exogenous factors
      (including pollution) influence the development of Hashimoto's
      thyroiditis/chronic lymphocytic thyroiditis (CLT). CLT may also be a risk factor
      for associated thyroid cancer. Few data are available on the role of pollution
      from petrochemical complexes, one of which is located in the Siracusa province
      (South-Eastern Sicily), in the pathogenesis of CLT. AIMS: i) To study the
      frequency of CLT in fine-needle aspiration cytology (FNAC)-interrogated thyroid
      nodules from patients who were stably resident in their zones, comparing it in
      patients living in the petrochemical complex area (zone A) with that of patients
      from a control area (zone B). ii) To study the frequency of CLT in the FNAC
      categories of malignancy risk, comparing the two zones. PATIENTS AND METHODS: We
      retrospectively evaluated cytologically adequate slides of 1323 nodules in 1013
      outpatients who underwent ultrasound-guided FNAC from 2006 to 2012. We stratified
      by area of residence, gender, and FNAC categories of malignancy risk. RESULTS:
      CLT was detected with significantly greater frequency in either patients or
      nodules from zone A compared with zone B (32.0% vs 23.1%, P=0.002 or 28.2% vs
      18.8%, P=0.0001), with a female preponderance (F=35.2% vs M=21.1% or 30.4% vs
      20.4%, zone A and F=26.5% vs 12.3% or 21.6% vs 9.5%, zone B). Regardless of zone,
      CLT was approximately twofold more frequent in the suspiciously
      malignant+malignant classes (TH4+THY5=47.6%, zone A and 32.4%, zone B) compared
      with the benign+intermediate classes (THY2+THY3=27.3%, zone A and 18.2%, zone B),
      but with a clear stepwise THY2 through THY5 increase only in zone A (THY2=25.3%,
      THY5=66.7%; THY2=18.6%, THY5=28.6% in zone B). CONCLUSIONS: The petrochemical
      complex-related pollution is an environmental factor involved in the development
      of CLT and, likely, in the CLT association with thyroid neoplasms.

PMID- 25599711
TI  - Evaluation of free-to-total prostate specific antigen (F/T PSA), prostate
      specific antigen density (PSAD) and (F/T)/PSAD sensitivity on reduction of
      unnecessary prostate biopsies for patients with PSA in gray zone.
AB  - AIM: We evaluated the influence of ratio between free-to-total prostate specific
      antigen (F/T PSA) and prostate specific antigen density (PSAD)-(F/T)/PSAD on
      reduction of unnecessary prostate biopsies in grey zone (prostate specific
      antigen (psa) value 4.0-10.0 ng/ml). METHODS: The study included 108 patients.
      For all patients serum total PSA (T PSA), free PSA (F PSA), F/T PSA and PSAD were
      analyzed. The group was divided due to the prostate volume into: entire group
      (regardless the prostate VOL-Group 1) and group with prostate VOL<40 (Group 2).
      RESULTS: Seventy five patients were diagnosed with benign prostatic hyperplasia
      (BPH) and 33 with prostate cancer (CaP). F/T PSA and (F/T)/PSAD showed
      significantly lower values in patients with CaP versus those with BPH, while PSAD
      had significantly higher values. For the cutoff values of 1.12 for (F/T)/PSAD, we
      found sensitivity to be 67% and specificity 60%, and the (AUC) 0.701. For
      patients with VOL<40, statistical significance remained with AUC of 0.732
      (p=0.003), cutoff was 0.82, and with sensitivity 77% and specificity 68%.
      CONCLUSIONS: Most significant prostate carcinoma predictors were PSAD and
      (F/T)/PSAD, where we proposed that patients with (F/T)/PSAD values below 1.49 +/-
      0.94 and PSAD values above 0.17+/-0.06 should be included for biopsy.

PMID- 25599712
TI  - Incorporation of personal single nucleotide polymorphism (SNP) data into a
      national level electronic health record for disease risk assessment, part 1: an
      overview of requirements.
AB  - BACKGROUND: Personalized medicine approaches provide opportunities for predictive
      and preventive medicine. Using genomic, clinical, environmental, and behavioral
      data, tracking and management of individual wellness is possible. A prolific way
      to carry this personalized approach into routine practices can be accomplished by
      integrating clinical interpretations of genomic variations into electronic
      medical records (EMRs)/electronic health records (EHRs). Today, various central
      EHR infrastructures have been constituted in many countries of the world
      including Turkey. OBJECTIVE: The objective of this study was to concentrate on
      incorporating the personal single nucleotide polymorphism (SNP) data into the
      National Health Information System of Turkey (NHIS-T) for disease risk
      assessment, and evaluate the performance of various predictive models for
      prostate cancer cases. We present our work as a miniseries containing three
      parts: (1) an overview of requirements, (2) the incorporation of SNP into the
      NHIS-T, and (3) an evaluation of SNP incorporated NHIS-T for prostate cancer.
      METHODS: For the first article of this miniseries, the scientific literature is
      reviewed and the requirements of SNP data integration into EMRs/EHRs are
      extracted and presented. RESULTS: In the literature, basic requirements of
      genomic-enabled EMRs/EHRs are listed as incorporating genotype data and its
      clinical interpretation into EMRs/EHRs, developing accurate and accessible
      clinicogenomic interpretation resources (knowledge bases), interpreting and
      reinterpreting of variant data, and immersing of clinicogenomic information into
      the medical decision processes. In this section, we have analyzed these
      requirements under the subtitles of terminology standards, interoperability
      standards, clinicogenomic knowledge bases, defining clinical significance, and
      clinicogenomic decision support. CONCLUSIONS: In order to integrate structured
      genotype and phenotype data into any system, there is a need to determine data
      components, terminology standards, and identifiers of clinicogenomic information.
      Also, we need to determine interoperability standards to share information
      between different information systems of stakeholders, and develop decision
      support capability to interpret genomic variations based on the knowledge bases
      via different assessment approaches.

PMID- 25599713
TI  - Validating a set of tools designed to assess the perceived quality of training of
      pediatric residency programs.
AB  - BACKGROUND: The Paediatric Residency Program (PRP) of Padua, Italy, developed a
      set of questionnaires to assess the quality of the training provided by each
      faculty member, the quality of the professional experience the residents
      experienced during the various rotations and the functioning of the Resident
      Affair Committee (RAC), named respectively: "Tutor Assessment Questionnaire"
      (TAQ), "Rotation Assessment Questionnaire" (RAQ), and RAC Assessment
      Questionnaire". The process that brought to their validation are herein
      presented. METHOD: Between July 2012 and July 2013, 51 residents evaluated 26
      tutors through the TAQ, and 25 rotations through the RAQ. Forty-eight residents
      filled the RAC Assessment Questionnaire. The three questionnaires were validated
      through a many-facet Rasch measurement analysis. RESULTS: In their final form,
      the questionnaires produced measures that were valid, reliable, unidimensional,
      and free from gender biases. TAQ and RAQ distinguished tutors and rotations into
      5-6 levels of different quality and effectiveness. The three questionnaires
      allowed the identification of strengths and weaknesses of tutors, rotations, and
      RAC. The agreement observed among judges was coherent to the predicted values,
      suggesting that no particular training is required for developing a shared
      interpretation of the items. CONCLUSIONS: The work herein presented serves to
      enrich the armamentarium of tools that resident medical programs can use to
      monitor their functioning. A larger application of these tools will serve to
      consolidate and refine further the results presented.

PMID- 25599714
TI  - Potential applications of induced pluripotent stem cells (iPSCs) in hepatology
      research.
AB  - Induced pluripotent stem cells (iPSCs) share many characteristics with embryonic
      stem cells (ESCs), but circumvent most of the ethical issues surrounding ESCs.
      The use of iPSCs to treat liver diseases is gaining increasing interest. Recent
      studies show these iPSCs can be differentiated into the hepatic lineage and
      provide an accurate model for liver diseases, drug screening and drug toxicity
      testing. Recently, the potential application of iPSC-derived hepatocytes to be
      used in cell-based therapies has been explored as a novel strategy to treat human
      liver disease. However, the successful use of these iPSC-derived hepatocytes
      hinges on overcoming the inherent problems of using iPSC in cell-based therapies.
      Given these problems are addressed in the future, these iPSC derived hepatocytes
      provide a limitless supply of cells that could be used to treat liver diseases
      not only in screening and toxicity testing but also in cell-based therapies. 

PMID- 25599715
TI  - Catastrophic health expenditures and its inequality in elderly households with
      chronic disease patients in China.
AB  - BACKGROUND: Although numerous studies examine catastrophic health expenditures
      (CHE) worldwide, most focus on whole populations rather than specific vulnerable
      groups. This study analyzes the extent, associated factors and inequality of CHE
      in elderly household with chronic disease patients in China. METHODS: Data were
      obtained from a nationally representative elderly household survey-the China
      Health and Retirement Longitudinal Study-that was conducted by the National
      School of Development of Peking University in 2011. An elderly household with
      chronic disease patients is defined by >= 1 chronic disease patient who is >= 45
      years of age. CHE was measured according to the proportion of out-of-pocket
      health payments to non-food household expenditures. The associated factors of CHE
      were estimated using ordinary least square and logistic regression modeling. CHE
      inequality was measured according to the concentration index (CI) and its
      decomposition. RESULTS: CHE incidence and intensity were relatively high among
      elderly households with chronic disease patients. The main associated factors of
      CHE include household size, having members > 65 years, having members with >= 2
      chronic diseases, per capita income, and elderly household members demonstrating
      healthcare-seeking behaviors. Healthcare insurance did not significantly affect
      CHE risk. Disproportionate concentration of CHE was noted among elderly
      households, and poor elderly households demonstrated a higher probability of
      experiencing CHE. Factors such as household size, per capita income, having
      members > 65 years, and having members with >= 2 chronic diseases are major and
      positive contributors to CHE inequality. Some inpatient and outpatient services
      are negatively contributed to CHE inequality,suggesting that the unequal usage of
      such services reduces CHE inequality among elderly households with chronic
      disease patients. CONCLUSION: Policy efforts should focus on improving financial
      protection and relieving the economic burden of disease in elderly households.
      The government should increase income subsidies and optimize social health
      insurance programs, thereby reducing CHE and alleviating CHE inequality among
      elderly households in China.

PMID- 25599716
TI  - In vivo endothelization of tubular vascular grafts through in situ recruitment of
      endothelial and endothelial progenitor cells by RGD-fused mussel adhesive
      proteins.
AB  - The use of tissue mimics in vivo, including patterned vascular networks, is
      expected to facilitate the regeneration of functional tissues and organs with
      large volumes. Maintaining patency of channels in contact with blood is an
      important issue in the development of a functional vascular network. Endothelium
      is the only known completely non-thrombogenic material; however, results from
      treatments to induce endothelialization are inconclusive. The present study was
      designed to evaluate the clinical applicability of in situ recruitment of
      endothelial cells/endothelial progenitor cells (EC/EPC) and pre-endothelization
      using a recombinant mussel adhesive protein fused with arginine-glycine-aspartic
      acid peptide (MAP-RGD) coating in a model of vascular graft implantation.
      Microporous polycaprolactone (PCL) scaffolds were fabricated with salt leaching
      methods and their surfaces were modified with collagen and MAP-RGD. We then
      evaluated their anti-thrombogenicity with an in vitro hemocompatibility
      assessment and a 4-week implantation in the rabbit carotid artery. We observed
      that MAP-RGD coating reduced the possibility of early in vivo graft failure and
      enhanced re-endothelization by in situ recruitment of EC/EPC (patency rate: 2/3),
      while endothelization prior to implantation aggravated the formation of
      thrombosis and/or IH (patency rate: 0/3). The results demonstrated that in situ
      recruitment of EC/EPC by MAP-RGD could be a promising strategy for vascular
      applications. In addition, it rules out several issues associated with pre
      endothelization, such as cell source, purity, functional modulation and
      contamination. Further evaluation of long term performance and angiogenesis from
      the luminal surface may lead to the clinical use of MAP-RGD for tubular vascular
      grafts and regeneration of large-volume tissues with functional vascular
      networks. 

PMID- 25599717
TI  - Positioning consensus for guidance.

PMID- 25599718
TI  - Triple antithrombotic therapy in atrial fibrillation patients with acute coronary
      syndromes or undergoing percutaneous coronary intervention or transcatheter
      aortic valve replacement.

PMID- 25599719
TI  - Standards of care: the EAPCI, guidelines and consensus documents.

PMID- 25599720
TI  - Closure of a secundum atrial septal defect in two infants with chronic lung
      disease using the Gore HELEX Septal Occluder.
AB  - Children with a secundum atrial septal defect are usually asymptomatic and are
      referred for elective closure after 3-4 years of age; however, in premature
      infants with chronic lung disease, bronchopulmonary dysplasia, or pulmonary
      hypertension, increased pulmonary blood flow secondary to a left-to-right atrial
      shunt, may exacerbate their condition. Closure of the atrial septal defect in
      these patients can result in significant clinical improvement. We report the
      cases of two premature infants with chronic lung disease, who underwent atrial
      septal defect closure with the Gore HELEX Septal Occluder and discuss the
      technical aspects of using the device in these patients and their clinical
      outcomes. 

PMID- 25599721
TI  - Erratum:  Penetration of (14C)-efinaconazole 10% solution does not appear to be
      influenced by nail polish.
AB  - [This corrects the article on p. 34 in vol. 7, PMID: 25276275.]. 

PMID- 25599722
TI  - Mental health related Internet use among psychiatric patients: a cross-sectional
      analysis.
AB  - BACKGROUND: The Internet is of great importance in today's health sector, as most
      Internet users utilize online functions for health related purposes. Concerning
      the mental health care sector, little data exist about the Internet use of
      psychiatric patients. It is the scope of this current study to analyze the
      quantity and pattern of Internet usage among mental health patients. METHODS:
      Patients from all services of the Department of Psychiatry at a university
      hospital were surveyed by completing a 29-item questionnaire. The data analysis
      included evaluation of frequencies, as well as group comparisons. RESULTS: 337
      patients participated in the survey, of whom 79.5% were Internet users. Social
      media was utilized by less than half of the users: social networks (47.8%),
      forums (19.4%), chats (18.7%), blogs (12.3%). 70.9% used the Internet for mental
      health related reasons. The contents accessed by the patients included:
      information on mental disorders (57.8%), information on medication (43.7%),
      search for mental health services (38.8%), platforms with other patients (19.8%)
      and platforms with mental health professionals (17.2%). Differences in the
      pattern of use between users with low, medium and high frequency of Internet use
      were statistically significant for all entities of social media (p < 0.01),
      search for mental health services (p = 0.017) and usage of platforms with mental
      health professionals (p = 0. 048). The analysis of differences in Internet use
      depending on the participants' type of mental disorder revealed no statistically
      significant differences, with one exception. Regarding the Internet's role in
      mental health care, the participants showed differing opinions: 36.2% believe
      that the Internet has or may have helped them in coping with their mental
      disorder, while 38.4% stated the contrary. CONCLUSIONS: Most psychiatric patients
      are Internet users. Mental health related Internet use is common among patients,
      mainly for information seeking. The use of social media is generally less
      frequent. It varies significantly between different user types and was shown to
      be associated with high frequency of Internet use. The results illustrate the
      importance of the Internet in mental health related contexts and may contribute
      to the further development of mental health related online offers.

PMID- 25599724
TI  - Female pseudohermaphroditism: strategy and bias in a fast diagnosis. How tricky
      could be a diagnosis with a wrong anamnesis.
AB  - AIM: Congenital genitalia anomalies are a spectrum of malformation, difficult to
      classify because similar or identical phenotypes could have several different
      aetiology; therefore it's essential to assess an efficient diagnostic algorithm
      for a quick diagnosis and to develop an efficient therapeutic strategy. The aim
      of this study is to underline the importance of imaging in case of ambiguous
      genitalia due to its high sensitivity and specificity in detecting internal
      organs and urogenital anatomy. MATERIAL OF STUDY: We report a case of a young
      girl affected by a complex genitor-urinary malformation with an initial wrong
      anamnesis that led to a tricky diagnosis. RESULTS: Imaging techniques -
      especially Magnetic Resonance Imaging (MRI) - together with karyotype, hormones
      and physical investigations, offered complete and reliable informations for the
      best surgical treatment of our patient. CONCLUSION: Karyotype, hormones
      investigation, and radiological examinations are the main criteria considered in
      the diagnostic iter. Ultrasonography (US) is the primary modality for the
      detection of the presence or absence of gonads and mullerian derivatives, whereas
      Cystourethrography can define urethral and vaginal tract or the presence of
      fistulas. In our experience MRI, due to its multiplanar capability and superior
      soft tissue characterization, proved to be useful to provide detailed anatomic
      information.

PMID- 25599723
TI  - The non-credible score of the Rey Auditory Verbal Learning Test: is it better at
      predicting non-credible neuropsychological test performance than the RAVLT
      recognition score?
AB  - The ability of both the non-credible score of the Rey Auditory Verbal Learning
      Test (RAVLT NC) and the recognition score of the RAVLT (RAVLT Recog) to predict
      credible versus non-credible neuropsychological test performance was examined.
      Credible versus non-credible group membership was determined according to
      diagnostic criteria with consideration of performance on two stand-alone
      performance validity tests. Findings from this retrospective data analysis of
      outpatients seen for neuropsychological testing within a Veterans Affairs Medical
      Center (N = 175) showed that RAVLT Recog demonstrated better classification
      accuracy than RAVLT NC in predicting credible versus non-credible
      neuropsychological test performance. Specifically, an RAVLT Recog cutoff of <=9
      resulted in reasonable sensitivity (48%) and acceptable specificity (91%) in
      predicting non-credible neuropsychological test performance. Implications for
      clinical practice are discussed. Note: The views contained here within are those
      of the authors and not representative of the institutions with which they are
      associated. 

PMID- 25599726
TI  - Correction announcement.
AB  - [This corrects the article on p. 1783 in vol. 9, PMID: 25422639.]. 

PMID- 25599725
TI  - Assessing fear of hypoglycemia in a population-based study among parents of
      children with type 1 diabetes - psychometric properties of the hypoglycemia fear
      survey - parent version.
AB  - BACKGROUND: In the treatment of childhood type 1 diabetes, being aware of the
      parents' fear of hypoglycemia is important, since the parents' fear may influence
      the management of treatment and the children's blood glucose regulation. The
      availability of proper instruments to assess the parents' fear of hypoglycemia is
      essential. Thus, the aim of this study was to examine the psychometric properties
      of the Hypoglycemia Fear Survey - Parent version (HFS-P). METHODS: In a Norwegian
      population-based sample, 176 parents representing 102 children with type 1
      diabetes (6-15 years old) completed the HFS-P, comprising a 15-item worry
      subscale and a 10-item behavior subscale. We performed exploratory and
      confirmatory factor analysis and further analysis of the scales' construct
      validity, content validity and reliability. RESULTS: The Norwegian version of the
      HFS-P had an acceptable factor structure and internal consistency for the worry
      subscale, whereas the structure and internal consistency of the behavior subscale
      was more questionable. The HFS-P subscales were significantly correlated (from
      moderately to weakly) with symptoms of emotional distress, as measured by the
      Hopkins Symptom Checklist - 25 items. The mothers scored higher than fathers on
      both HFS-P subscales, but the difference was not statistically significant for
      the worry subscale. CONCLUSIONS: The HFS-P worry subscale seems to be a valid
      scale for measuring anxiety-provoking aspects of hypoglycemia, and the validity
      of the HFS-P behavior subscale needs to be investigated further.

PMID- 25599727
TI  - Using business intelligence to analyze and share health system infrastructure
      data in a rural health authority.
AB  - BACKGROUND: Health care organizations gather large volumes of data, which has
      been traditionally stored in legacy formats making it difficult to analyze or use
      effectively. Though recent government-funded initiatives have improved the
      situation, the quality of most existing data is poor, suffers from
      inconsistencies, and lacks integrity. Generating reports from such data is
      generally not considered feasible due to extensive labor, lack of reliability,
      and time constraints. Advanced data analytics is one way of extracting useful
      information from such data. OBJECTIVE: The intent of this study was to propose
      how Business Intelligence (BI) techniques can be applied to health system
      infrastructure data in order to make this information more accessible and
      comprehensible for a broader group of people. METHODS: An integration process was
      developed to cleanse and integrate data from disparate sources into a data
      warehouse. An Online Analytical Processing (OLAP) cube was then built to allow
      slicing along multiple dimensions determined by various key performance
      indicators (KPIs), representing population and patient profiles, case mix groups,
      and healthy community indicators. The use of mapping tools, customized shape
      files, and embedded objects further augment the navigation. Finally, Web forms
      provide a mechanism for remote uploading of data and transparent processing of
      the cube. For privileged information, access controls were implemented. RESULTS:
      Data visualization has eliminated tedious analysis through legacy reports and
      provided a mechanism for optimally aligning resources with needs. Stakeholders
      are able to visualize KPIs on a main dashboard, slice-and-dice data, generate ad
      hoc reports, and quickly find the desired information. In addition, comparison,
      availability, and service level reports can also be generated on demand. All
      reports can be drilled down for navigation at a finer granularity. CONCLUSIONS:
      We have demonstrated how BI techniques and tools can be used in the health care
      environment to make informed decisions with reference to resource allocation and
      enhancement of the quality of patient care. The data can be uploaded immediately
      upon collection, thus keeping reports current. The modular design can be expanded
      to add new datasets such as for smoking rates, teen pregnancies, human
      immunodeficiency virus (HIV) rates, immunization coverage, and vital statistical
      summaries.

PMID- 25599728
TI  - Role of high-density lipoprotein cholesterol in renovascular disease treatment.

PMID- 25599729
TI  - Drug-induced acute interstitial nephritis: pathology, pathogenesis, and
      treatment.
AB  - Drug-induced acute interstitial nephritis (DAIN) is a common cause of acute
      kidney injury and often presents as an unexplained rise in serum creatinine
      level. Kidney biopsy is therefore frequently required to make a definitive
      diagnosis. The hallmark pathologic features of DAIN are interstitial edema,
      interstitial inflammation, and tubulitis with a predominance of CD4+ T
      lymphocytes and mononuclear cells, with variable numbers of eosinophils. This is
      a result of a type B idiosyncratic non-immunoglobulin-E-mediated immune reaction
      marked by cell-mediated immune injury to the renal tubulointerstitium. The drug
      becomes immunogenic via various mechanisms such as haptenization, antigen
      mimicry, and neo-antigen formation. Renal interstitial dendritic cells, and renal
      tubular epithelial cells play an important role in further propagating this
      immunologic injury. Acute DAIN can progress within days to weeks to a chronic
      form triggered by fibroblast activation and manifested as interstitial fibrosis
      and tubular atrophy. The mainstay of treatment of DAIN is discontinuation of the
      offending drug. Incomplete renal recovery is seen in one-third of the patients
      and depends on the duration of injury prior to diagnosis. Use of steroids for
      treatment of DAIN makes biological sense, but lack of randomized controlled
      trials and conflicting data from retrospective studies makes the approach
      unclear. Positive effects include faster recovery of kidney function, more
      complete recovery with less chronic kidney disease, and reduced need for chronic
      dialysis. Therefore, it seems reasonable to employ corticosteroids in patients
      that do not rapidly improve 3 to 5 days following discontinuation of the
      offending agent. 

PMID- 25599731
TI  - Medullary sponge kidney diagnosed by unenhanced magnetic resonance imaging.

PMID- 25599730
TI  - Herbs and hazards: risk of aristolochic acid nephropathy in Iran.
AB  - Herbs are usually considered as inherently harmless products. Nonetheless,
      various renal injuries have been reported in association with several herbs. The
      best-known herb-induced chronic kidney disease is aristolochic acid nephropathy.
      Aristolochic acid is found in Chinese slim herbs. Balkan endemic nephropathy is
      nowadays considered as an aristolochic acid nephropathy. Plants of
      Aristolochiaceae (also known as birthwort, dutchman's pipe, and somersworth) is
      named zaravand or chopoghak in Persian and it grows in different mountainous and
      rural areas of Iran. The fruit and the steam of the Aristolochiacae are named
      zaravand gerd (nokhod alvand) and zaravand dearaz, respectively, and have
      different usage in Iranian teadirional such as treatment of headache, back pain,
      and anxiety. Some patients with end-stage renal disease and bilateral small
      kidneys have a history of exposure to some herbal remedies. We need to consider
      the possibility of environmental toxins and even Aristolochia nephrotoxicity as a
      potential danger in Iran. 

PMID- 25599732
TI  - Predictive accuracy of urinary beta2-microglobulin for kidney injury in children
      with acute pyelonephritis.
AB  - INTRODUCTION: Leukocyte count, erythrocyte sediment rate and C-reactive protein
      are available laboratory markers which may be helpful in prediction of technetium
      Tc 99m dimercaptosuccinic acid (DMSA) renal scintigraphy results. None of these,
      however, have enough accuracy for prediction of renal injury and scar. This study
      was aimed to evaluate the diagnostic accuracy of urinary beta2-microglobulin in
      detection of renal injury in children with acute pyelonephritis. MATERIALS AND
      METHODS: Eighty-nine children between 2 months and 14 years old with the
      diagnosis of acute pyelonephritis that had no past history of infection in the
      urinary tract system were enrolled in the study. A standard urine sample
      according to patients' age was obtained for urine culture, urinalysis, and
      urinary beta2-microglobulin tests. Blood sample was obtained for leukocyte count,
      creatinine, blood urea nitrogen, C-reactive protein, erythrocyte sediment rate,
      and electrolytes tests. All patients underwent DMSA scan. RESULTS: The cutoff
      point for urinary beta2-microglubulin for prediction of positive DMSA scan was
      0.8 mg with a sensitivity of 40.9% (95% CI, 26.3% to 56.8%) and a specificity of
      84.1% (95% CI, 69.9% to 93.4%), a positive predictive value of 72.0% (95% CI,
      50.6% to 87.9%) and an negative predictive value of 58.7% (95% CI, 45.6% to
      71.0%). CONCLUSIONS: Urinary beta2-microglobulin is not enough sensitive and
      specific to be used as a diagnostic marker for prediction of renal injury. Other
      common markers such as erythrocyte sediment rate, leukocyte count, and C-reactive
      protein can be used in combination to predict kidney injury in children with
      acute pyelonephritis.

PMID- 25599733
TI  - Association between NPHS1 and NPHS2 gene variants and nephrotic syndrome in
      children.
AB  - INTRODUCTION: Nephrin and podocin proteins, encoded by NPHS1 and NPHS2 genes, are
      essential for the integrity of the glomerular filter. The present study was aimed
      to investigate whether NPHS1 rs437168 and NPHS2 rs61747728 genetic variants are
      involved in the susceptibility to nephrotic syndrome (NS). MATERIALS AND METHODS:
      This case-control study was performed on 108 children with NS and 97 healthy
      children. Genomic DNA was extracted from whole blood using the salting-out
      method. Polymorphism of the NPHS1 rs437168 and NPHS2 rs61747728 were detected by
      amplification refractory mutation system- and tetra primers amplification
      refractory mutation system-polymerase chain reaction, respectively. RESULTS: The
      results showed that the NPHS1 rs437168 GA as well as GA+AA genotypes increased
      the risk of NS in comparison with GG genotype (odds ratio, 4.76, 95% confidence
      interval, 2.31 to 9.80; P < .001 and odds ratio, 4.57; 95% confidence interval,
      2.31 to 9.04, ; P < .001, respectively). The A allele was associated with
      increased risk of NS (odds ratio, 3.53; 95% confidence interval, 1.94 to 6.42, ;
      P < .001) in comparison to the G allele. No association was observed between
      NPHS2 rs61747728 polymorphism and NS. CONCLUSIONS: Our findings indicate that
      NPHS1 rs437168, but not NPHS2 rs61747728 variant, is associated with NS.

PMID- 25599734
TI  - Prognostic factors in crescentic glomerulonephritis: a single-center experience.
AB  - INTRODUCTION: Crescentic glomerulonephritis (CGN) is a fatal disease, rapidly
      leading to end-stage renal disease. Diagnosis should be accurate and treatment
      should be started immediately. We investigated the factors associated with the
      renal prognosis in CGN patients. MATERIALS AND METHODS: Forty-one patients with
      CGN who were followed up at the Nephrology Clinic of Ankara Numune Education and
      Research Hospital were divided into 2 arms of the dialysis-dependent group after
      treatment and the group that was followed up without dialysis. Demographic and
      clinical features along with biopsy findings during time of diagnosis were
      evaluated for both groups. RESULTS: The mean age was 41.3 +/- 17.2 years old and
      26 were men. Twenty patients developed end-stage renal disease, requiring long
      term dialysis. The dialysis-dependent group had higher serum creatinine levels
      (8.2 +/- 3.6 mg/dL versus 2.6 +/- 2.5 mg/dL) and percentages of glomeruli with
      crescent (83.1 +/- 19.1% versus 56.4 +/- 11.9%), were more likely to have
      oligoruia-anuria (90.5% versus 9.5%) and be dialysis-dependent at admission
      (86.4% versus 13.6%), and had longer elapsed time until the beginning of
      treatment (18.9 +/- 10.4 days versus 10.6 +/- 3.0 days) after treatment. At
      admission, their serum creatinine was greater than 4.2 mg/dL and the rate of
      crescentic glomeruli was greater than 63%. CONCLUSIONS: In patients with CGN,
      renal prognosis is poor and the time of admission to the hospital, degree of
      renal insufficiency, presence of oligo-anuria, dialysis requirement, and the
      percentage of crescentic glomeruli on biopsy are closely related to progression
      to end-stage renal disease.

PMID- 25599735
TI  - Association of high-density lipoprotein cholesterol with improvement of
      endothelial dysfunction recovery in renovascular disease.
AB  - INTRODUCTION: This study was aimed to assess the ratio of total cholesterol (TC)
      to high-density density lipoprotein cholesterol (HDLC) and plasma nitrate levels
      in patients with ischemic nephropathy receiving statins and niacin extended
      release (NER). MATERIALS AND METHODS: Kidney disease patients with a history of
      at least 5 year of diabetes mellitus or 10 year of hypertension were screened by
      renal artery Doppler ultrasonography. Participants were randomly assigned into
      two groups to receive atorvastatin, 20 mg/d, with and without NER, 500 mg/d, for
      16 weeks. Serum levels of lipid profile, creatinine, and nitrate were compared
      before and after the study. RESULTS: Fifty-four patients received the statin and
      51 received statin-NER combination. Both statin and statin-NER groups
      demonstrated significant decreases in plasma levels of TC and low-density
      lipoprotein cholesterol. Triglyceride and very low-density lipoprotein
      cholesterol were significantly lowered only with statin-NER combination. The
      increase in HDLC level was found in both groups, but significant only with statin
      NER combination therapy (P < .001). Atorvastatin combined with NER reduced
      TC/HDLC ratio almost double as compared with that of atorvastatin alone (102% and
      36.6% reduction, respectively). A similar pattern was observed for nitrate levels
      (33% and 65%, respectively). CONCLUSIONS: These findings indicated that a
      reduction in TC/HDLC ratio improves endothelial function in renovascular disease
      and use of NER in combination with atorvastatin may provide better outcomes. This
      could be helpful in attenuating further vascular damage and associated systemic
      complications.

PMID- 25599736
TI  - Correlation between serum level of fibroblast growth factor 2 and severity of
      reflux nephropathy.
AB  - INTRODUCTION: Fibroblast growth factor 2 (FGF2) is a potent mitogenic factor of
      cortical fibroblasts and induces kidney fibrosis. We hypothesized that serum
      levels of FGF2 has an association with the severity of vesicoureteral reflux
      (VUR) and renal parenchymal scar. MATERIALS AND METHODS: Between 2007 and 2009, a
      total of 28 children with VUR were enrolled in this study and were compared with
      52 healthy children. All children with VUR underwent technetium Tc 99m
      dimercaptosuccinic acid renal scintigraphy. Fibroblast growth factor 2 was
      measured in both groups. RESULTS: The mean level of FGF2 was 65.0 +/- 19.0 pg/mL
      in the VUR group and 62.5 +/- 15.3 pg/mL in the control group (P > .05). There
      was no correlation between serum levels of FGF2 and sex, age, or the grade of
      VUR. Of the 28 children with VUR, 19 had renal parenchymal scar on
      dimercaptosuccinic acid renal scintigraphy. The mean serum level of FGF2 was not
      significantly different in the children with and without renal parenchymal scar.
      CONCLUSIONS: This study showed no correlation between serum FGF2 and renal
      parenchymal scar or grade of VUR.

PMID- 25599737
TI  - Low-dose pamidronate for treatment of early bone loss following kidney
      transplantation: a randomized controlled trial.
AB  - INTRODUCTION: Kidney transplantation is associated with rapid loss of bone
      mineral density (BMD) in the first months after transplantation. The effect of
      pamidronate on bone loss after transplantation was evaluated in a randomized
      controlled trial. MATERIALS AND METHODS: Forty patients were enrolled in this
      study (16 in the pamidronate group and 24 in the control group). Pamidrinate was
      administered as 30-mg intravenous infusion within 2 days after transplantation
      and 3 months later. All of the patients received calcium and vitamin D
      supplementation. Laboratory parameters and BMD (lumbar spine and femoral neck)
      were measured at baseline and 6 months after kidney transplantation. RESULTS:
      Bone mineral density at the initiation of study had no significant differences
      between the two groups. In each group, BMD of femoral neck and lumbar spine had
      no significant differences 6 months after transplantation in comparison to
      pretransplantation values. There was no significant difference in BMD changes
      after intervention between two groups. Parathyroid hormone level normalized in
      both of the pamidronate and control groups 6 months after kidney transplantation.
      Glomerular filtration rate at the end of study was not significantly different
      between the two groups. CONCLUSIONS: Our study suggests that administration of
      calcium and vitamin D following transplantation may be beneficial to
      counterbalance the substantial bone loss occurring within 6 months after
      transplantation, and addition of pamidronate has no beneficial effect in BMD in
      this short interval after kidney transplantation.

PMID- 25599739
TI  - Cystinuria in a patient with a novel mutation in SLC7A9 gene.
AB  - Cystinuria, one of the first inborn errors of metabolism, is characterized by
      hyperexcretion of cystine, arginine, lysine, and ornithine into urine. Cystinuria
      is genetically classified into types A and B. Mutations in the SLC3A1 gene lead
      to type A, and type B is caused by mutations in the SLC7A9 gene. We described a
      19-year-old woman that had early onset of cystine calculus formation at the age
      of 3 years. After DNA extraction and polymerase chain reaction, direct sequencing
      was performed. By these methods, a novel nucleotide substitution c.177G>A in exon
      3 of the SLC7A9 gene was found, which had not been reported elsewhere previously.
      This nucleotide substitution occurs in the extracellular domain of the SLC7A9
      gene. In addition, a previously described intron variant c.1136+2/3delT (intron 6
      of SLC3A1) in homozygosity status was detected in the patient. To our knowledge,
      this is the first report of novel nucleotide substitution c.177G>A in exon 3 of
      the SLC7A9 gene. 

PMID- 25599738
TI  - Effect of N-acetyl cysteine and vitamin C on kidney allograft function biomarkers
      interleukin-18 and neutrophil gelatinase-associated lipocalin.
AB  - INTRODUCTION: Delayed graft function (DGF) is a consequence of ischemia
      reperfusion injuries in kidney allografts, for which no definite treatment is
      available. The neutrophil gelatinase-associated lipocalin (NGAL) and interleukin
      18 (IL-18) are introduced as the most promising urine biomarkers to detect DGF. N
      acetylcysteine (NAC) and vitamin C, well-known potent antioxidants that scavenge
      free radicals, may alleviate kidney injury. This study investigated the
      protective effects of NAC alone and in combination with vitamin C on DGF, by
      measuring IL-18 and NGAL in living donor kidney transplantations. MATERIALS AND
      METHODS: Patients transplanted between January 2011 and February 2013 were
      randomly divided into 3 groups to receive routine anti-rejection medication only
      (n = 32), NAC plus routine immunosuppressive regimen (NAC group; n = 33), and NAC
      and vitamin C plus routine regimen (NAC and vitamin C group; n = 19). Urine
      samples were taken 4 hours and 24 hours after transplantation. Enzyme-linked
      immunosorbent assay kits were utilized for measuring urine NGAL and IL-18.
      RESULTS: There were no significant differences in the DGF prevalence and its
      duration between the study arms. Although the levels of NGAL and IL-18 decreased
      in the NAC and NAC and vitamin C groups, these reductions were not significant.
      Glomerular filtration rate at 30 and 60 days after transplantation were not
      significantly different between study groups, either. CONCLUSIONS: Our results
      showed that NAC is a safe drug without significant adverse effects in kidney
      transplant recipients; however, its potential useful effects on urinary
      biomarkers of DGF were not illustrated in the present study.

PMID- 25599740
TI  - Successful treatment of calciphylaxis with pamidronate.
AB  - Calciphylaxis is a complication of chronic kidney disease characterized by
      necrotic lesion in the skin. Histological examination reveals microcalcification
      of medium-sized blood vessels. We report on a 21-month-old girl with end-stage
      renal disease with severe calcium-phosphate imbalance. Calciphylaxis process
      started when she received calcium gluconate intravenously the day before the
      surgery to correct hypocalcemia and continued progressively despite peritoneal
      dialysis and forced stopping calcium-containing medication. Pamidronate, 0.5
      mg/kg/d, was administered for 6 days and then once a week for 5 weeks. After 1
      week, the skin lesion started to heal and circulation improved, and after 6
      weeks, all skin lesions completely recovered. Pamidronate was effective to stop
      calciphylaxis in this case with advanced renal insufficiency and severe calcium
      phosphate imbalance. Medical or surgical debridement are not suggested and
      lesions might recover without scar by pamidronate.

PMID- 25599742
TI  - Technology contribution to prevention of noncommunicable diseases.

PMID- 25599741
TI  - Familial Mediterranean fever E148Q mutation, episodic fever and kidney allograft
      dysfunction.

PMID- 25599743
TI  - Re: kidney function and metabolic profile of chronic kidney disease and
      hemodialysis patients during Ramadan fasting.

PMID- 25599744
TI  - Erratum.

PMID- 25599745
TI  - QT prolongation and torsades de pointes in a patient with heart block and a
      pacemaker.
AB  - Prolongation of the QT interval and development of torsades de pointes are known
      in patients with complete heart block and profound bradycardia. We report the
      case of a patient with complete heart block and torsades, with long QT seen
      during a period of junctional tachycardia at a rate faster than the minimum
      pacemaker rate. 

PMID- 25599746
TI  - Meningoencephalitis caused by Plesiomonas shigelloides in a Chinese neonate: case
      report and literature review.
AB  - The most usual presentation of Plesiomonas shigelloides infection is an acute
      gastroenteritis, and extraintestinal manifestations are extremely rare. We
      reported the first neonate with P. shigelloides meningoencephalitis in China and
      reviewed the twelve cases previously reported. Our report adds further awareness
      on Plesiomonas shigelloides meningoencephalitis in neonate and points out the
      importance of an early diagnosis and the use of sensitive antibiotics treatment
      to this fatal infection. 

PMID- 25599747
TI  - Efficacy of platelet-rich plasma injections in pain associated with chronic
      tendinopathy: A systematic review.
AB  - BACKGROUND: Chronic tendinopathy has often been a management dilemma for general
      practitioners. With our understanding of the pathophysiology of tendinopathy
      evolving, so has our management, with the advent of newer strategies such as
      topical glycerol trinitrate, extracorporeal shock-wave therapy, as well as
      platelet-rich plasma (PRP). AIM: To systematically review the literature
      regarding PRP therapy in chronic tendinopathy. DESIGN AND SETTING: The databases
      used in our search include the Elton B. Stephens Co. (EBSCO) database, Medline,
      the Cochrane library, Ovid, and Embase (the Excerpta Medica database). A total of
      389 articles were reviewed from Feb 2010 to April 2014, for possible inclusion.
      Of these articles, a total of 9 randomized controlled trials (RCTs) met our
      inclusion criteria. Only 1 RCT was excluded due to previous surgery in both the
      trial and control groups. METHODS: Each article was reviewed independently by 2
      authors. Each article was analyzed using the Cochrane Criteria checklist. Where
      any discrepancy occurred in results, a third independent reviewer was consulted.
      RESULTS: Our review found that PRP was most effective in patellar and lateral
      epicondylar tendinopathy, with both RCTs in the patellar section of our study
      supporting the use of PRP in pain reduction at 3 and 12 months, whereas 2 of 4
      studies in the lateral epicondylar section showed improvements in pain and
      disability at 6 and 12 months. There was a lack of evidence to support the use of
      PRP in Achilles and rotator cuff tendinopathy. CONCLUSIONS: Although the results
      of this review show promise for the use of PRP in chronic tendinopathy, the
      analysis highlighted the need for more controlled clinical trials comparing PRP
      with placebo.

PMID- 25599749
TI  - Corrigendum: Quantifying the Protection of Activating and Inhibiting NK Cell
      Receptors during Infection with a CMV-Like Virus.
AB  - [This corrects the article on p. 20 in vol. 5, PMID: 24523722.]. 

PMID- 25599748
TI  - Comparison of montelukast and cabergoline for prevention of ovarian
      hyperstimulation syndrome: in an experimental rat model.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication
      that can occur during assisted reproductive techniques. The aim of this study is
      to investigate the effects of the leukotriene receptor antagonist (montelukast)
      treatment in prevention of OHSS and compare to cabergoline treatment. Twenty-four
      immature female Wistar rats were assigned to four groups. Group 1 was the control
      group. In the remaining three groups, OHSS was induced through ovarian
      stimulation with gonadotropins. No treatment was given to Group 2. Group 3 was
      administered a low-dose 100 mg/kg cabergoline treatment and Group 4 was received
      20 mg/kg montelukast. Body weight, ovarian weight, vasculary permability (VP),
      peritoneal fluid vascular endothelial growth factor (VEGF) values and VEGF immune
      expression were compared between the groups. Both cabergoline and montelukast
      prevented progression of OHSS compared to the OHSS group. Body weight, ovarian
      weight, VP, peritoneal fluid VEGF values and VEGF expression were significantly
      lower in both cabergoline- and montelukast-treated rats than in those not treated
      OHSS group. In conclusion, montelukast is an effective option for prevention of
      OHSS, as well as cabergoline. Montelukast may be a new treatment option to
      prevent and control the OHSS.

PMID- 25599750
TI  - Pegylated IFN-alpha-2a and ribavirin in the treatment of hepatitis C infection in
      children.
AB  - The epidemiology, natural history and efficacy of treatment for chronic hepatitis
      C in children are presented. An increase in the number of vertical infections of
      this etiology is suggested. In children, especially in those vertically infected,
      spontaneous elimination of hepatitis C virus (HCV) is observed more often than it
      is in adults. The most common HCV genotype detected in children is genotype 1,
      but Italian researchers have described an increase of infection with genotypes 3
      and 4 HCV in children in recent years. In the context of recent opinions
      suggesting a more rapid progression of HCV 3 genotype infection, treatment of
      these children should begin immediately. The high efficacy (sustained viral
      response > 50%), safety (few adverse events with less intensity as compared to
      adults) and good tolerance of therapy with pegylated IFN alpha-2a and ribavirin
      have been revealed in children. The differences in the efficacy and tolerability
      of HCV treatment between children and adults are described. A recommendation for
      inclusion and monitoring parameters of children's physical and mental development
      during HCV treatment is presented. Regarding new anti-HCV therapies with very
      high efficacy, including IFN-free treatment, the introduction of these therapies
      to children is recommended. 

PMID- 25599751
TI  - Oxidative stress as a pharmacological target for medicinal chemistry: synthesis
      and evaluation of compounds with redox activity - part 2.

PMID- 25599752
TI  - The effects of auditive and visual settings on perceived restoration likelihood.
AB  - Research has so far paid little attention to how environmental sounds might
      affect restorative processes. The aim of the present study was to investigate the
      effects of auditive and visual stimuli on perceived restoration likelihood and
      attitudes towards varying environmental resting conditions. Assuming a condition
      of cognitive fatigue, all participants (N = 40) were presented with images of an
      open plan office and urban nature, each under four sound conditions (nature
      sound, quiet, broadband noise, office noise). After the presentation of each
      setting/sound combination, the participants assessed it according to restorative
      qualities, restoration likelihood and attitude. The results mainly showed
      predicted effects of the sound manipulations on the perceived restorative
      qualities of the settings. Further, significant interactions between auditive and
      visual stimuli were found for all measures. Both nature sounds and quiet more
      positively influenced evaluations of the nature setting compared to the office
      setting. When office noise was present, both settings received poor evaluations.
      The results agree with expectations that nature sounds and quiet areas support
      restoration, while office noise and broadband noise (e.g. ventilation, traffic
      noise) do not. The findings illustrate the significance of environmental sound
      for restorative experience. 

PMID- 25599753
TI  - Is rosuvastatin protective against on noise-induced oxidative stress in rat
      serum?
AB  - Noise, one of the main components of modern society, has become an important
      environmental problem. Noise is not only an irritating sound, but also a stress
      factor leading to serious health problems. In this study, we have investigated
      possible effects of rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor, thought to have an antioxidant effect, on noise-induced
      oxidative stress in the serum of rat models. Thirty-two male Wistar albino rats
      were used. In order to ease their adaptation, 2 weeks before the experiment, the
      rats were divided into four groups (with eight rats per each group): Noise
      exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage
      and control. After the data had been collected, oxidant (Malondialdehyde, nitric
      oxide [NO], protein carbonyl [PC]) and antioxidant (superoxide dismutase [SOD],
      glutathione peroxidase [GSH-PX], catalase [CAT]) parameters were analyzed in the
      serum. Results indicated that SOD values were found to be significantly lower,
      while PC values in serum were remarkably higher in the group that was exposed to
      only noise. GSH-Px values in serum dramatically increased in the group on which
      only rosuvastatin was used. During noise exposure, the use of rosuvastatin caused
      significantly increased CAT values, whereas it resulted in reduced PC and NO
      values in serum. In conclusion, our data show that noise exposure leads to
      oxidative stress in rat serum; however, rosuvastatin therapy decreases the
      oxidative stress caused by noise exposure. 

PMID- 25599754
TI  - Effects of noise and acoustics in schools on vocal health in teachers.
AB  - Previous studies on the influence of noise and acoustics in the classroom on
      voice symptoms among teachers have exclusively relied on self-reports. Since self
      reported physical conditions may be biased, it is important to determine the role
      of objective measurements of noise and acoustics in the presence of voice
      symptoms. To assess the association between objectively measured and self
      reported physical conditions at school with the presence of voice symptoms among
      teachers. In 12 public schools in Bogotalpha, we conducted a cross-sectional
      study among 682 Colombian school workers at 377 workplaces. After signed the
      informed consent, participants filled out a questionnaire on individual and work
      related conditions and the nature and severity of voice symptoms in the past
      month. Short-term environmental measurements of sound levels, temperature,
      humidity, and reverberation time were conducted during visits at the workplaces,
      such as classrooms and offices. Logistic regression analysis was used to
      determine associations between work-related factors and voice symptoms. High
      noise levels outside schools (odds ratio [OR] = 1.83; 95% confidence interval
      [CI]: 1.12-2.99) and self-reported poor acoustics at the workplace (OR = 2.44;
      95% CI: 1.88-3.53) were associated with voice symptoms. We found poor agreement
      between the objective measurements and self-reports of physical conditions at the
      workplace. This study indicates that noise and acoustics may play a role in the
      occurrence of voice symptoms among teachers. The poor agreement between objective
      measurements and self-reports of physical conditions indicate that these are
      different entities, which argue for inclusion of physical measurements of the
      working environment in studies on the influence of noise and acoustics on vocal
      health. 

PMID- 25599755
TI  - Long-term noise exposure and the risk for type 2 diabetes: a meta-analysis.
AB  - Diabetes mellitus is one of the leading causes for disability and mortality in
      modern societies. Apart from personal factors its incidence might be influenced
      by environmental risks such as air pollution and noise. This paper reports a
      systematic review and meta-analysis on the risk for type 2 diabetes due to long
      term noise exposure. Electronic searches in MEDLINE, EMBASE and the Internet
      yielded 9 relevant studies (5 for residential and 4 for occupational exposure).
      They were checked against a predefined list of safeguards against bias producing
      individual quality scores, which were then fed to MetaXL to conduct a quality
      effects meta-analysis. People exposed at their homes to roughly L(den) > 60 dB
      had 22% higher risk (95% confidence interval [CI]: 1.09-1.37) for type 2 diabetes
      in comparison to those exposed to L(den) < 64 dB; when studies reporting
      contentious exposure categories were excluded, there was still 19% risk (95% CI:
      1.05-1.35) for L(den) = 60-70 dB versus L(den) < 60 dB. In occupational
      environment there was not significant risk (relative risk [RR] = 0.91, 95% CI:
      0.78-1.06) for < 85 dB versus >85 dB. There was no heterogeneity in the two
      groups (I2 = 0.00). The results should be interpreted with caution due to
      methodological discrepancies across the studies; however, they are indicative of
      the close links that noise pollution might have not only to cardiovascular
      diseases but to endocrine dysfunction as well.

PMID- 25599757
TI  - Dose - response relationship between noise exposure and the risk of occupational
      injury.
AB  - Many workers worldwide experience fatality and disability caused by occupational
      injuries. This study examined the relationship between noise exposure and
      occupational injuries at factories in Korea. A total of 1790 factories located in
      northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels
      of dust and noise exposure were taken from Workplace Exposure Assessment data.
      Apart occupational injuries, sports events, traffic accidents, and other
      accidents occurring outside workplaces were excluded. The incidences of
      occupational injury in each factory were calculated by data from the Korea
      Workers' Compensation and Welfare Services. Workplaces were classified according
      to the incidence of any occupational injuries (incident or nonincident
      workplaces, respectively). Workplace dust exposure was classified as <1 or >= 1
      mg/m3 , and noise exposure as <80, 80-89, or >90 dB. Workplaces with high noise
      exposure were significantly associated with being incident workplaces, whereas
      workplaces with high dust exposure were not. The odds ratios (95% confidence
      intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and
      3.42 (2.26-5.17) at 80-89 dB and >= 90 dB versus <80 dB. These associations
      remained significant when in a separate analysis according to high or low dust
      exposure level. Noise exposure increases the risk of occupational injury in the
      workplace. Furthermore, the risk of occupational injury increases with noise
      exposure level in a dose-response relationship. Therefore, strategies for
      reducing noise exposure level are required to decrease the risk of occupational
      injury.

PMID- 25599759
TI  - Erratum: figure correction.
AB  - [This corrects the article on p. 124 in vol. 12, PMID: 25191502.]. 

PMID- 25599758
TI  - Noise levels in an urban Asian school environment.
AB  - Background noise is known to adversely affect speech perception and speech
      recognition. High levels of background noise in school classrooms may affect
      student learning, especially for those pupils who are learning in a second
      language. The current study aimed to determine the noise level and teacher speech
      to-noise ratio (SNR) in Hong Kong classrooms. Noise level was measured in 146
      occupied classrooms in 37 schools, including kindergartens, primary schools,
      secondary schools and special schools, in Hong Kong. The mean noise levels in
      occupied kindergarten, primary school, secondary school and special school
      classrooms all exceeded recommended maximum noise levels, and noise reduction
      measures were seldom used in classrooms. The measured SNRs were not optimal and
      could have adverse implications for student learning and teachers' vocal health.
      Schools in urban Asian environments are advised to consider noise reduction
      measures in classrooms to better comply with recommended maximum noise levels for
      classrooms. 

PMID- 25599756
TI  - Hearing loss associated with US military combat deployment.
AB  - The objective of this study was to define the risk of hearing loss among US
      military members in relation to their deployment experiences. Data were drawn
      from the Millennium Cohort Study. Self-reported data and objective military
      service data were used to assess exposures and outcomes. Among all 48,540
      participants, 7.5% self-reported new-onset hearing loss. Self-reported hearing
      loss showed moderate to substantial agreement (k = 0.57-0.69) with objective
      audiometric measures. New-onset hearing loss was associated with combat
      deployment (adjusted odds ratio [AOR] = 1.63, 95% confidence interval [CI] = 1.49
      1.77), as well as male sex and older age. Among deployers, new-onset hearing loss
      was also associated with proximity to improvised explosive devices (AOR = 2.10,
      95% CI = 1.62-2.73) and with experiencing a combat-related head injury (AOR =
      6.88, 95% CI = 3.77-12.54). These findings have implications for health care and
      disability planning, as well as for prevention programs. 

PMID- 25599760
TI  - Time-use patterns and the recreational use of prescription medications among
      rural and small town youth.
AB  - PURPOSE: To examine the relationship between rural and small town adolescents'
      time-use and an increased risk for recreational use of prescription drugs in
      rural settings. METHODS: Rural students in grades 9 and 10 (n = 2,393) were asked
      about past-year recreational use of prescription medications and their time-use
      in structured and unstructured activity contexts in the 2009/2010 Cycle of the
      Canadian Health Behaviour in School-aged Children survey. Time-use patterns of
      rural and small town youth from across Canada were examined using multilevel,
      multivariate Poisson regression analyses to determine whether they may impact the
      risk of this kind of substance use. FINDINGS: Peer time outside school hours and
      nonparticipation in extracurricular activities were significantly associated with
      rural youths' recreational use of prescription drugs. Peer drug use, unhappy home
      lives and frequent binge drinking explained most of these associations.
      CONCLUSIONS: Structured and unstructured activity contexts within rural settings
      play a role in the nonmedical use of prescription medications. Results support
      interventions aimed at increasing structured time-use opportunities in addition
      to focusing on peer contexts and multiple risk-taking behaviors among rural
      youth.

PMID- 25599763
TI  - Duration of post-traumatic amnesia as a predictor of functional outcome in school
      age children: a systematic review.
AB  - AIM: In adults, duration of post-traumatic amnesia (PTA) is a powerful early
      predictor of functional outcomes in traumatic brain injury. The aim of this work
      was to assess the predictive validity of PTA duration for outcomes in children (6
      18y). METHOD: PsycINFO, MEDLINE, Web of Science, and Embase were searched for
      papers published to January 2014. Ten studies met inclusion criteria: they used
      standardized instruments to assess PTA and functional outcomes, and examined
      relationships between the two. Outcomes were classified according to (1) the
      International Classification of Functioning, Disability and Health (ICF) core
      sets for neurological conditions for post-acute care and (2) global functioning
      and quality of life. Methodological quality was rated for each study. RESULTS:
      The search identified 10 studies of moderate mean quality (M=11.8 out of 18).
      Longer PTA duration related to worse functional outcomes: global functioning and
      in the two ICF categories ('body function', 'activities and participation').
      Relationships between PTA duration and quality of life and the ICF category of
      'body structure' were not examined. PTA duration was, in 46 out of 60 (76.67%)
      instances, a stronger predictor of outcomes than other indices of injury
      severity. CONCLUSION: Longer PTA duration is a valid predictor of worse outcomes
      in school-age children. Thus, PTA should be routinely assessed in children after
      traumatic brain injury.

PMID- 25599761
TI  - Survival of dental implants in patients with oral cancer treated by surgery and
      radiotherapy: a retrospective study.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the survival of
      dental implants placed after ablative surgery, in patients affected by oral
      cancer treated with or without radiotherapy. METHODS: We collected data for 34
      subjects (22 females, 12 males; mean age: 51 +/- 19) with malignant oral tumors
      who had been treated with ablative surgery and received dental implant
      rehabilitation between 2007 and 2012. Postoperative radiation therapy (less than
      50 Gy) was delivered before implant placement in 12 patients. A total of 144
      titanium implants were placed, at a minimum interval of 12 months, in irradiated
      and non-irradiated residual bone. RESULTS: Implant loss was dependent on the
      position and location of the implants (P = 0.05-0.1). Moreover, implant survival
      was dependent on whether the patient had received radiotherapy. This result was
      highly statistically significant (P < 0.01). Whether the implant was loaded is
      another highly significant (P < 0.01) factor determining survival. We observed
      significantly better outcomes when the implant was not loaded until at least 6
      months after placement. CONCLUSIONS: Although the retrospective design of this
      study could be affected by selection and information biases, we conclude that a
      delayed loading protocol will give the best chance of implant osseointegration,
      stability and, ultimately, effective dental rehabilitation.

PMID- 25599765
TI  - Erratum.
AB  - [This corrects the article on p. 558 in vol. 13, PMID: 24358008.]. 

PMID- 25599764
TI  - Very late follow-up of a passive defibrillator lead under recall: do failure
      rates increase during long-term observation.
AB  - BACKGROUND: The Medtronic Sprint Fidelis lead (SFL; Medtronic Inc., Minneapolis,
      MN, USA) has a significantly impaired long-term survival, and active fixation
      leads fare worse than passive leads. The goal of this study was to present data
      of a series of passive SFL only with very long mean follow-up of more than 6
      years. METHODS: Patients in whom a passive SFL was implanted in two large Swiss
      centers were followed. We excluded eight (5.5%) patients with a follow-up of <6
      months. Patients who died or were lost during follow-up were censored at death or
      last device check, all others on January 31, 2014. We employed two different
      definitions of failure: strict = fracture with inappropriate discharge; sudden
      increase in impedance >1,500 or high-voltage impedance >100 Ohm; >300
      nonphysiological short interventricular-intervals. Lenient = any of the above
      plus a linear increase in impedance >1,500 Ohm or a linear decrease in sensing to
      a level that treating cardiologists considered inappropriate. RESULTS: We
      included 137 patients. Age was 60 +/- 12 years. Mean and median follow-up were
      6.2 +/- 2.1 and 6.8 (interquartile range 4.8-7.8) years. Applying the strict
      definition, 12 leads (8.8%) were replaced after 4.9 +/- 2.4 years (range 1.2
      8.1). Applying the lenient definition, 14 leads (10.2%) failed. Cumulative lead
      survival was 98.5% at 3, 96.9% at 4, 94.2% at 5, and 93.1% at 6 years. Leads "at
      risk" were: n = 122 (89%), 115 (84%), 101 (74%), and 88 (64%). CONCLUSIONS: In
      this population with passive SFLs, 5-year lead survival is impaired with 94.2%
      based on 74% of leads "at risk" at this time point.

PMID- 25599766
TI  - Effects of grass hay proportion in a corn silage-based diet on rumen digesta
      kinetics and digestibility in dairy cows.
AB  - In this study, we aimed to evaluate the effects of six levels of orchardgrass hay
      (GH) proportion (0%, 10%, 20%, 30%, 40% or 50% of dry matter) in finely chopped
      corn silage (CS)-based diets on digesta kinetics of CS and GH in the rumen. Six
      non-lactating, rumen-cannulated Holstein cows were used in a 6 * 6 Latin square
      design. Ruminal digesta kinetics was measured by ruminal dosing of feed particle
      markers (dysprosium for CS, erbium for GH) followed by fecal sampling. The
      increase of GH proportion had a quadratic effect (P < 0.01) on total tract
      digestibility of neutral detergent fiber (NDF) and acid detergent fiber. The
      proportion of GH did not affect the particle size distribution of rumen digesta,
      total weight of dry matter or NDF in the rumen. The rates of large particle size
      reduction in the rumen for CS tended to increase linearly with increasing GH
      proportion (P = 0.077). A quadratic effect (P < 0.05) was found with increasing
      the GH proportion for the ruminal passage rate of small GH particles, but not for
      CS particles. The results suggested that associative effects between CS and GH
      could be generated on rumen digesta kinetics when cows were fed a CS-based diet
      with an increased proportion of GH.

PMID- 25599767
TI  - Hypothalamic expression of oestrogen receptor alpha and androgen receptor is sex
      , age- and region-dependent in mice.
AB  - Sex steroid hormones act on developing neural circuits regulating the
      hypothalamic-pituitary-gonadal axis and are involved in hormone-sensitive
      behaviours. These hormones act mainly via nuclear receptors, such as oestrogen
      receptor (ER)-alpha and androgen receptor (AR). By using immunohistochemistry, we
      analysed the expression level of ERalpha and AR throughout perinatal life [at
      embryonic (E) day 19 and postnatal (P) days 5, 15 and 25] and in adulthood in
      several hypothalamic nuclei controlling reproduction in both wild-type and
      aromatase knockout (ArKO) (i.e. which cannot convert testosterone into
      oestradiol) mice to determine whether there are sex differences in hypothalamic
      ERalpha and AR expression and, if so, whether these are established by the action
      of oestradiol. As early as E19, ERalpha immunoreactivity (-IR) was observed at
      same expression levels in both sexes in the anteroventral periventricular nucleus
      (AVPv), the medial preoptic area (MPOA), the bed nucleus of the stria terminalis
      (BnST), the ventrolateral part of the ventromedial hypothalamic nucleus and the
      arcuate nucleus (ARC). Sex differences (female > male) in ERalpha-IR were
      observed not only during the prepubertal period in the BnST (P5 to P25) and the
      MPOA (P15), but also in adulthood in these two brain regions. Sex differences in
      AR-IR (male > female) were observed at P5 in the AVPv and ARC, and at P25 in the
      MPOA and ARC, as well as in adulthood in all hypothalamic regions analysed. In
      adulthood, gonadectomy and hormonal treatment (oestradiol or dihydrotestosterone)
      also strongly modulated ERalpha-IR and AR, respectively. Taken together, sex
      differences in ERalpha-IR and AR-IR were observed in all hypothalamic regions
      analysed, although they most likely do not reflect the action of oestradiol
      because ArKO mice of both sexes showed expression levels very similar to wild
      type mice throughout perinatal development. 

PMID- 25599768
TI  - Clostridium difficile infection and inflammatory bowel disease.
AB  - Over the past 15 years, Clostridium difficile infection (CDI) in patients with
      inflammatory bowel disease (IBD) has increased both in incidence and severity.
      Traditional risk factors for CDI are similar in IBD and non-IBD populations, but
      there is a significant proportion of IBD patients which have distinctive
      characteristics. Patients with ulcerative colitis (UC) are more susceptible to
      CDI and have more severe outcomes than those with Crohn's disease (CD). CDI may
      be difficult to distinguish from an IBD flare due to similar clinical
      presentation, and therefore screening for CDI is recommended at every flare in
      such patients. Several studies showed worse clinical outcomes in IBD patients
      with CDI, including longer hospital stay, higher colectomy and mortality rates
      than in those without CDI. Vancomycin and metronidazole appear to have similar
      efficacy in patients with moderate disease, but vancomycin is preferred in severe
      disease. Measures must be taken to prevent the spread of infection. Clinicians
      should have a high index of suspicion for CDI when evaluating a patient with IBD
      flare, as rapid detection and prompt treatment of infection improve outcomes.
      This review summarizes the available literature on epidemiology, risk factors,
      clinical aspects, diagnostic methods, treatment, outcome, and prevention of CDI
      in IBD patients. 

PMID- 25599769
TI  - Serum gastrin levels in different stages of distal gastric carcinogenesis: is
      there a role for serum gastrin in tumor growth?
AB  - BACKGROUND/AIMS: Elevated levels of serum gastrin (SG) have been associated with
      tumorigenic effects in a number of gastrointestinal cancers. We decided to
      investigate the relationship between SG and gastric epithelial lesions. MATERIALS
      AND METHODS: A total of 90 patients with gastric epithelial lesions (hyperplastic
      polyp, 12; adenoma, 41; early gastric cancer, 29; advanced gastric cancer, 8)
      were enrolled as the case group and 79 patients without epithelial lesions were
      enrolled as the control group. RESULTS: Serum gastrin levels were significantly
      different between the case and control groups (p<0.001). A high SG level (>80
      pg/mL), intestinal metaplasia, and a pepsinogen I/II ratio <3 were independently
      associated with an increased risk of epithelial lesions (odds ratio: 14.6, 9.4,
      and 4.1, respectively, p<0.05). SG levels in case subjects showed a unimodal
      distribution pattern as the disease progressed. The mean SG level was highest in
      those with hyperplastic polyps and then decreased significantly to the control
      level in the gastric cancer group. Higher SG levels in each disease category were
      not associated with increased tumor size, synchronicity, invasiveness, presence
      of lymph node metastasis, or a higher cellular proliferation index (p>0.05).
      CONCLUSION: An increased SG level was an independent and potent risk factor for
      gastric epithelial lesions. However, it does not seem to relate with distal
      gastric tumor growth. Serial decreases in SG levels should be considered a
      warning sign in index hypergastrinemic patients with no prior Helicobacter pylori
      eradication.

PMID- 25599771
TI  - Is concomitant cholecystectomy with laparoscopic sleeve gastrectomy safe?
AB  - BACKGROUND/AIMS: To study the effect of selective concomitant cholecystectomy
      (SCC) on laparoscopic sleeve gastrectomy (LSG). MATERIALS AND METHODS: A
      retrospective case-control study of 16 morbidly obese patients treated with
      concomitant LSG as the primary bariatric surgery and SCC for proven gallbladder
      (GB) pathology (Group A) between November 2010 and February 2013 was performed.
      Randomly selected 32 patients who underwent laparoscopic sleeve gastrectomy was
      the control group (Group B). RESULTS: A total of 48 patients with a mean age of
      35.5+/-10.7 years were included. Demographic data of groups were similar except
      that there were more female patients in the Group A (p=0.036). Mean body mass
      index (kg/m2) was 51.1+/-5.6 and 50.9+/-5.4 in Groups A and B, respectively
      (p=0.894). The mean operative time for patients with and without cholecystectomy
      was 157.2+/-40 and 95.72+/-6.2 min, respectively (p=0.001). Cholecystectomy
      resulted in an additional mean operative time of 49.1+/-27.9 min without any
      specific complication. There was no statistical difference with regard to overall
      morbidity (p=0.316) and the length of hospital stay (p=0.528) between groups.
      CONCLUSION: Although an increase in operative time may be an important issue, SCC
      can be performed on all patients with proven GB pathology during LSG without an
      increase in morbidity or length of hospital stay.

PMID- 25599770
TI  - Process of technical stabilization of gastric endoscopic submucosal dissection at
      the National Cancer Center in Japan.
AB  - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) was originally developed
      in 1995 using an insulation-tipped diathermic knife (Olympus, Tokyo, Japan) to
      achieve en-bloc resection of early gastric cancer (EGC). It has been suggested
      that advances in endoscopic devices and medical equipment, such as the high
      frequency generator (1999) and hemostatic forceps (2000), and procedural
      improvements including post-ESD preventive coagulation of visible vessels in the
      resection area (2003) led to further progress of ESD; therefore, we investigated
      the actual process of technical stabilization of gastric ESD. MATERIALS AND
      METHODS: A total of 1,713 consecutive patients with solitary differentiated-type
      EGC at initial onset underwent ESD at our hospital from 1995 to 2006. We
      retrospectively assessed ESD outcomes for all patients by dividing them into
      three chronological periods: 1995-1998 (1st period; 57 patients), 1999-2002 (2nd
      period; 563 patients), and 2003-2006 (3rd period; 1,093 patients). RESULTS: The
      en-bloc resection, intraoperative bleeding, and delayed bleeding in the
      1st/2nd/3rd period were 52.6%/94.7%/99.3% (1st vs. 2nd, p<0.01; 2nd vs. 3rd,
      p<0.01), 8.8%/7.1%/1.6% (1st vs. 2nd, no significant difference; 2nd vs. 3rd,
      p<0.01), and 15.8%/7.6%/3.3% (1st vs. 2nd, p<0.05; 2nd vs. 3rd, p<0.01),
      respectively. CONCLUSION: Gastric ESD has stabilized technically following
      advances in endoscopic devices and medical equipment together with procedural
      improvements.

PMID- 25599772
TI  - The role of Bifidobacterium lactis B94 plus inulin in the treatment of acute
      infectious diarrhea in children.
AB  - BACKGROUND/AIMS: In contrast to many other studies of probiotic species, the
      number of publications evaluating Bifidobacterium lactis and its combinations
      with prebiotics as treatments for acute infectious diarrhea is limited. We
      investigated the synbiotic effects of B. lactis B94 plus inulin on acute
      infectious diarrhea. MATERIALS AND METHODS: The study was conducted on children
      with acute diarrhea between the ages of 2 and 60 months. The patients were
      administered 5*1010 colony-forming units (CFU) of B. lactis B94 plus 900 mg
      inulin or placebo, once a day for five days. Stools were examined for Rotavirus,
      Adenovirus, Entamoeba histolytica, Salmonella, Shigella, Campylobacter,
      Clostridium difficile, Cryptosporidium, and parasites. RESULTS: We examined 79
      patients in the synbiotic group and 77 patients in the placebo group. The
      duration of diarrhea was significantly reduced in the synbiotic group in
      comparison with the placebo group (3.9+/-1.2 days vs. 5.2+/-1.3 days,
      respectively; p<0.001). Moreover, the number of diarrheal stools on the third day
      was significantly lower in the synbiotic group than in the placebo group (5.5+/
      2.9 vs. 8.3+/-3.01, respectively; p<0.001). Diarrhea in the synbiotic-group
      patients with rotavirus infection was of a significantly shorter duration (3.2+/
      1.3 days vs. 5.2+/-1.3 days, respectively; p=0.001). Duration of diarrhea in
      patients who started the synbiotic treatment within the first 24 h was shorter
      than that in the patients who started the treatment later (3.9+/-1.1 days vs.
      4.8+/-1.8 days, respectively; p=0.002). CONCLUSION: Treatment with 5 * 1010 CFU
      of B. lactis B94 plus 900 mg inulin shortened the duration of acute watery
      diarrhea by an average of 31 h. This decrease was most pronounced in cases of
      Rotavirus diarrhea.

PMID- 25599773
TI  - NADPH oxidase p22phox gene expression in ulcerative colitis.
AB  - BACKGROUND/AIMS: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase,
      which catalyzes the formation of reactive oxygen species (ROS) in phagocytic
      cells, has five subunits: p67phox ("phox"refers to "phagocyte oxidase"), p47phox,
      p40phox, p22phox, and gp91phox (catalytic subunit). Oxidative stress resulting
      from the accumulation of ROS and/or defective removal of ROS by antioxidants has
      detrimental effects on cellular functions and may contribute to chronic
      inflammation. Disruption of the colonic mucosa due to the dysregulation of
      antioxidants or transformation enzymes may play a role in the pathogenesis of
      ulcerative colitis (UC) and influence the clinical features of this disease. In
      this study, we examined the expression of the gene encoding NADPH oxidase subunit
      p22phox cytochrome b-245, alphapolypeptidein the colonic mucosa to test its
      possible contribution in the pathogenesis of UC. MATERIALS AND METHODS:
      Expression levels of mRNA in the inflamed and non-inflamed colonic mucosa
      (determined using colonoscopy)of 22 patients with UC and in the normal mucosa of
      22 healthy controls were analyzed using real-time polymerase chain reaction.
      RESULTS: Expression levels of mRNA were not significantly different between
      patients with inflamed and non-inflamed colonic mucosa (p>0.05) and
      betweenpatients with inflamed colonicmucosa and healthy controls (p>0.05).
      CONCLUSION: Although our data suggest that expression of the gene encoding
      p22phox is not associated with chronic inflammation in patients with UC, other
      mechanisms can affect oxidative stress in these patients.

PMID- 25599774
TI  - No association between the functional cannabinoid receptor type 2 Q63R variants
      and inflammatory bowel disease in Turkish subjects.
AB  - BACKGROUND/AIMS: The endocannabinoid system can exert beneficial effects on
      gastrointestinal inflammation, and cannabinoid receptor-2 (CB2) agonists may
      represent a new therapeutic approach in inflammatory bowel disease (IBD). A
      functional CB2 Q63R polymorphism (rs35761398) in the CNR2 gene has been shown to
      affect the immunomodulating properties of the CB2 receptor. We sought to
      investigate whether the functional CB2 Q63R polymorphism (rs35761398) is
      associated with IBD susceptibility in a Turkish clinical sample. MATERIALS AND
      METHODS: A total of 202 IBD patients, comprising 101 Crohn's disease (CD)
      patients and 101 ulcerative colitis (UC) patients, and 101 healthy controls were
      included in the study. The CB2 Q63R polymorphism was genotyped using real-time
      PCR. RESULTS: There were no significant differences in the genotype frequencies
      of the three study groups. The odds ratio of the minor Q allele for CD relative
      to the common R allele was not significant (OR =1.02, 95% CI =0.67-1.56, p=0.99).
      Similarly, the odds ratio of the minor Q allele for UC relative to the common R
      allele did not reach statistical significance (OR =1.10, 95% CI =0.72-1.68,
      p=0.75). Moreover, the genotype frequencies did not show any significant
      association with the disease extent in either CD (p= 0.71) or UC patients
      (p=0.59). CONCLUSION: These pilot findings suggest that CB2 Q63R polymorphism
      does not play a major role in genetic susceptibility to IBD or in its disease
      phenotypes among Turkish subjects.

PMID- 25599776
TI  - Effects of a kefir supplement on symptoms, colonic transit, and bowel
      satisfaction score in patients with chronic constipation: a pilot study.
AB  - BACKGROUND/AIMS: Although probiotics have been extensively studied in irritable
      bowel syndrome, data on the impact of probiotics on chronic constipation are
      scarce. We aimed to evaluate the effects of kefir, which is a probiotic fermented
      milk product, on the symptoms, colonic transit, and bowel satisfaction scores of
      patients with chronic constipation. MATERIALS AND METHODS: Twenty consecutive
      patients with functional constipation according to the Rome II criteria were
      divided into two groups based on their colon transit studies: 1. The normal
      transit (NT) group (n=10); and 2. The slow transit (ST) group (n=10). After a
      baseline period, 500 mL/day of a probiotic kefir beverage was administered to all
      patients for 4 weeks. Defecation parameters (stool frequency, stool consistency,
      degree of straining, laxative consumption) were recorded in diaries daily by the
      patients. Bowel satisfaction scores were assessed using a visual analog scale.
      The colon transit study was repeated in the ST group at the end of the study.
      RESULTS: At the end of the study, the patients showed an increased stool
      frequency (p<0.001), improved stool consistency (p=0.014), and decreased laxative
      consumption (p=0.031). The degree of straining during evacuation showed a
      tendency to improve after kefir administration; however, this was not
      statistically significant (p=0.18). A repeat transit study showed an acceleration
      of colonic transit in the ST group (p=0.013). Bowel satisfaction scores also
      improved (p<0.001). CONCLUSION: This pilot study shows that kefir has positive
      effects on the symptoms of constipation. Our results also suggest that kefir
      improves bowel satisfaction scores and accelerates colonic transit. Controlled
      trials are warranted to confirm these findings.

PMID- 25599777
TI  - Clinical impact of endoscopic ultrasonography for small rectal neuroendocrine
      tumors.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) is helpful for evaluating the
      depth of tumor invasion and lymph node metastasis of rectal neuroendocrine tumors
      (NETs). The aim of this study was to clarify the clinical impact of EUS for
      rectal NETs less than 10 mm in diameter. MATERIALS AND METHODS: A total of 76
      rectal NETs treated at our hospital between June 2006 and March 2013 were
      reviewed retrospectively. All lesions were analyzed with EUS to evaluate the
      depth of tumor invasion. The lesions were resected by endoscopic submucosal
      resection with band ligation (ESMR-L) or endoscopic submucosal dissection (ESD)
      and examined histologically. RESULTS: Endoscopic ultrasonography findings showed
      that all lesions were confined to the submucosa and revealed no adjacent lymph
      node metastasis. Seventy-five of the 76 lesions were completely resected by ESMR
      L. One lesion was resected by ESD and the resected deep margin of the lesion was
      histologically positive. Only one lesion exhibited lymphatic invasion.
      CONCLUSION: EUS may not be essential for diagnosis and treatment planning for
      rectal NETs less than 10 mm in size.

PMID- 25599775
TI  - Ketamine versus alfentanil combined with propofol for sedation in colonoscopy
      procedures: a randomized prospective study.
AB  - BACKGROUND/AIMS: Different drug combinations are used for sedation in colonoscopy
      procedures. A ketamine-propofol (ketofol) mixture provides effective sedation and
      has minimal adverse effects. Alfentanil also provides anesthesia for short
      surgical procedures by incremental injection as an adjunct. However, no study has
      investigated the use of ketofol compared with an opioid-propofol combination in
      colonoscopic procedures. MATERIALS AND METHODS: A total of 70 patients, ASA
      physical status I-II, scheduled to undergo elective colonoscopy, were enrolled in
      this prospective randomized study and allocated to two groups. After
      premedication, sedation induction was performed with 0.5 mg/kg ketamine +1 mg/kg
      propofol in Group KP, and 10 mg/kg alfentanil +1 mg/kg propofol in Group AP.
      Propofol was added when required. Demographic data, colonoscopy duration,
      recovery time, discharge time, mean arterial pressure (MAP), heart rate (HR),
      peripheral oxygen saturation, Ramsey Sedation Scale values, colonoscopy patients'
      satisfaction scores, and complications were recorded. RESULTS: The need for
      additional propofol doses was significantly higher in Group AP than in Group KP.
      MAP at minute 1 and 5, Ramsey Sedation Scale at minute 5, and discharge time were
      significantly higher in Group KP than in Group AP. Additional propofol doses and
      total propofol dose were significantly lower in Group KP than in Group AP.
      CONCLUSION: Ketofol provided better hemodynamic stability and quality of sedation
      compared with alfentanil-propofol combination in elective colonoscopy, and
      required fewer additional propofol; however, it prolonged discharge time. Both
      combinations can safely be used in colonoscopy sedation.

PMID- 25599778
TI  - Location of rectal cancer as determined using rectal magnetic resonance imaging,
      and its relationship with pulmonary metastasis.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the accuracy of 3-T
      magnetic resonance imaging (MRI) in locating rectal cancer, and to determine
      whether tumor location correlates with the incidence of pulmonary metastasis.
      MATERIALS AND METHODS: A total of 146 patients with confirmed rectal
      adenocarcinoma underwent 3-T rectal MRI, and abdominal and chest computed
      tomography (CT) within 2 weeks of the endoscopic examination. We reviewed the
      distance between the mass and the anal verge recorded in the endoscopic reports
      of these patients. Two radiologists evaluated the same distance on MRI scans by
      using picture archiving and communications systems. Multiple factors including
      the tumor location, primary tumor and lymph node stage, lung and liver
      metastasis, pathologic differentiation, and the carcinoembryonic antigen level
      were evaluated. The correlation between tumor location on MRI and endoscopy was
      assessed, and significant factors influencing pulmonary metastasis were
      identified using multivariate logistic regression analysis. RESULTS: There was a
      statistically significant correlation between the tumor location established
      using MRI and the actual location recorded during endoscopy. The incidence of
      pulmonary metastasis was significantly higher in patients with lower rectal
      cancer (11/17, 65%) compared to those with upper rectal cancer (6/17, 35%;
      p<0.05). Factors associated with pulmonary metastasis were tumor location and the
      presence of liver metastasis. CONCLUSION: The accurate tumor location could be
      indicated using 3-T rectal MRI. Pulmonary metastasis occurred more frequently in
      patients with lower rectal cancer than in those with upper rectal cancer.

PMID- 25599779
TI  - Staging of rectal carcinoma: MDCT, MRI or EUS. Single center experience.
AB  - BACKGROUND/AIMS: To retrospectively compare the efficacy of multidetector
      computed tomography (MDCT), magnetic resonance imaging (MRI) and endosonography
      (EUS) in the staging of rectal carcinoma. MATERIALS AND METHODS: A total of 50
      patients (36 male, 14 female) were included in the study. The data from surgical
      staging were used as reference for comparing the yield of EUS, MRI, and MDCT in
      preoperative T and N staging of rectal carcinoma. Comparisons were based on the
      chi-square test. RESULTS: The mean age+SD of the patients were 60+/-12 years
      (range; 28-80). The distribution of rectal tumors according to the T and N
      staging in surgical pathology was as following: T1 (n:2), T2 (n:15), T3 (n:22),
      T4 (n:11); N0 (n:22), N1-2 (n:28). The accuracy rate of EUS was statistically
      higher than that of MDCT (92% vs 64%; p<0.01) and that of MRI (92% vs 72%;
      p<0.01) for T2 tumors. For T3 tumors, EUS had statistically better accuracy of
      staging compared to MDCT (90% vs 58%; p<0.01) and MRI (90% vs 60%; p<0.01). As
      for T4 tumors, the accuracy rate of EUS was higher compared to MRI (98% vs 80%;
      p<0.01). There was no statistical difference in accuracy rates for detection of
      lymph nodes across the modalities (EUS, 84%; MDCT 76%; MRI 70%; p=not
      significant). CONCLUSION: EUS appears more accurate in T staging compared to MDCT
      and MRI in rectal carcinoma. Regarding nodal staging, performance of EUS, MDCT
      and MRI are similar.

PMID- 25599781
TI  - Myocardial integrated ultrasonic backscatter for early detection of cardiac
      involvement in patients with Wilson disease.
AB  - BACKGROUND/AIMS: Videodensitometry is a feasible noninvasive ultrasound tissue
      characterization method allowing early detection of myocardial changes. This
      study aimed to investigate ultrasonic backscatter properties of the myocardium in
      Wilson disease patients. MATERIALS AND METHODS: We compared cardiologically
      asymptomatic Wilson disease patients (W group) (n=18) with age-matched (26.7+/
      9.6 years) healthy controls (C group) (n=15). Diagnosis of Wilson disease was
      made on the basis of clinical manifestations, family history, and laboratory
      findings and confirmed by liver biopsy. Transthoracic echocardiographic
      quantitative texture analysis was performed on data from the septum and left
      ventricular posterior wall, and mean gray level (MGL) histograms at end-diastole
      (d) and end-systole (s) were obtained after background correction (c). Cyclic
      variation index (CVI) was calculated using the formula [(cMGLd - cMGLs) / cMGLd]
      *100. RESULTS: There were no significant differences in sex, age, body mass
      index, heart rate or blood pressure, and conventional echocardiographic
      parameters between the 2 groups. The cMGLs value of the posterior wall was higher
      in the W group than in the C group (30.9+/-2.6 vs. 22.2+/-2.7, p=0.033). The W
      group had a significantly lower CVI of the septum than did the C group (-22+/
      4.4% vs. 43.4 +/-12.9%, p<0.001), and there was no significant difference in the
      CVI of the posterior wall (-67.0+/-15.9% vs. 41.7+/-18.6%, p=0.32). CONCLUSION:
      Abnormalities in two-dimensional echocardiographic grey-level distributions were
      present in Wilson disease patients. These videodensitometric myocardial
      alterations were significantly lower in Wilson disease patients than in the
      controls, and this probably represents an early stage of cardiac involvement.

PMID- 25599780
TI  - Experimental study on the effects of massive bowel resection on liver function
      and hepatocyte apoptosis.
AB  - BACKGROUND/AIMS: The effects of short-bowel syndrome on liver function and liver
      morphology independent of parenteral nutrition have not been thoroughly
      investigated. Our aim was to investigate the effects of massive bowel resection
      on hepatocyte apoptosis and liver function in rats. MATERIALS AND METHODS: A
      total of 37 female Sprague-Dawley rats were randomly assigned to five groups:
      Control (no procedure); Sham 1 [laparotomy (LT)/enterotomy (ET); evaluated on
      postoperative day (POD) 1]; Sham 2 (LT/ET; evaluated on POD7; Group 1 (80% bowel
      resection after LT/ET; POD1); and Group 2 (80% bowel resection; POD7). Blood
      samples were obtained for measuring aspartate aminotransferase, alanine
      aminotransferase, and lactate dehydrogenase levels. For assessing hepatocyte
      apoptosis, liver tissue samples from the median lobe were obtained and used for a
      terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling
      assay. RESULTS: Aspartate aminotransferase, alanine aminotransferase, and lactate
      dehydrogenase levels showed statistically significant differences among the five
      groups. Apoptotic hepatocyte counts there were statistically significant
      differences among groups for counts made in 20 consecutive high-power fields.
      However, liver sinusoidal cell apoptosis rates among groups showed statistically
      significant differences for counts made in 20 consecutive high-power fields,
      particularly on POD7 in rats undergoing massive bowel resection. CONCLUSION:
      Parenteral nutrition is not the only factor involved in liver dysfunction after
      massive bowel resection. Massive bowel resection alone can cause liver
      abnormalities. Rats undergoing massive small intestinal resection show
      significant temporal increases in liver sinusoidal cell apoptosis rates.

PMID- 25599782
TI  - The efficacy and safety of tenofovir in the prevention of hepatitis B virus
      recurrence following liver transplantation.
AB  - BACKGROUND/AIMS: In this study, a tenofovir disoproxil fumarate (TDF) + hepatitis
      B immunoglobulin (HBIG) regimen was compared with lamivudine (LAM) + HBIG to
      determine the efficacy and safety of TDF in the prevention of hepatitis B virus
      (HBV) recurrence following liver transplantation (LT). MATERIALS AND METHODS:
      Thirty-six patients, 18 treated with TDF+HBIG (TDF group) and 18 with LAM+HBIG
      (LAM group), were evaluated retrospectively over a median 36-month follow-up in
      the Liver Transplantation Outpatient Unit of Dokuz Eylul University after having
      an LT. In the TDF group, TDF treatment was initiated in six patients due to
      resistance to LAM, in one patient due to relapse, in three patients to prevent
      relapse, and in eight patients due to de novo hepatitis. In the LAM group, LAM
      therapy was initiated in two patients due to de novo hepatitis and in 16 patients
      to prevent relapse. RESULTS: In the TDF group, an increase of greater than 0.5
      mg/dL in creatinine values was observed in two patients. In the LAM group,
      creatinine values did not increase to greater than 0.5 mg/dL. No cases of acute
      renal failure associated with TDF or LAM, mild or serious adverse events, or HBV
      recurrence were observed among the patients. Glomerular filtration rates (GFRs)
      of these patients were calculated with a modification of renal disease (MDRD)
      formulation. There was no significant difference (p<0.05) in the GFRs between the
      two groups. CONCLUSION: The results of this study, after a 36-month follow-up
      period, were encouraging and demonstrated that TDF therapy is safe and
      efficacious in treating HBV-positive organ transplant patients. However, patients
      should be monitored carefully in terms of renal function. Given the limited
      experience with TDR in LT, this study is of importance due to its long follow-up
      period.

PMID- 25599783
TI  - Is it necessary to re-evaluate diagnostic criteria for Wilson disease in
      children?
AB  - BACKGROUND/AIMS: The differential diagnosis of Wilson Disease (WD) is
      challenging, especially in children, because liver copper levels may also
      increase in other chronic liver diseases with bile stasis. The aim of this study
      is to determine urine and liver copper cut-off values to differentiate WD from
      other chronic liver diseases (non-WD, NWD) in children. MATERIALS AND METHODS:
      Seventy-six patients participated in the study, 35 with WD and 41 with NWD. The
      two groups were divided into two subgroups according to the presence of
      cholestasis. At the time of diagnosis, age, sex, biochemical test results, serum
      ceruloplasmin, baseline 24-h urinary copper levels, liver biopsy histological
      findings, liver copper levels, and Child-Pugh scores were obtained from medical
      records. Copper content in liver tissue and copper levels in urine were measured
      by atomic absorption spectrometry. Cut-off values for differentiation of WD from
      NWD were determined by receiver operating characteristic (ROC) analysis. RESULTS:
      A liver copper cut-off value of 98 ug/g indicated WD with 91% sensitivity and
      65.4% specificity (area under the curve =0.838, 95% CI: 0.749-0.927). A 24-h
      urinary copper cut-off value of 67.5 ug/24h indicated WD with 85% sensitivity and
      71% specificity (area under the curve =0.843, 95% CI: 0.752-0.934). CONCLUSION:
      In this study of pediatric chronic liver disease patients, copper cut-off values
      for distinguishing WD differed substantially from those used for diagnosis. A
      larger scale study is warranted to re-evaluate liver copper and 24-h urinary
      copper cut-offs for children with suspected WD.

PMID- 25599784
TI  - Clinical features in liver cirrhosis patients who have experienced ischemic
      stroke.
AB  - BACKGROUND/AIMS: The actual incidence of ischemic stroke in patients with liver
      cirrhosis remains controversial. The aim of this study was to analyze the
      clinical features of patients with liver cirrhosis who have experienced ischemic
      stroke. MATERIALS AND METHODS: A retrospective analysis was performed on the
      medical records of 23 ischemic stroke cases who were also diagnosed with liver
      cirrhosis, over a 10 year period from January 2001 to December 2010. RESULTS:
      Using the Child-Pugh classification system, Class B (39%) was the most common
      among the liver cirrhosis patients with ischemic stroke. There were six patients
      who presented with Class C (26%). Alcohol was analyzed as the main cause for
      liver cirrhosis in 14 patients (60.8%). Among the risk factors of ischemic
      stroke, nine of the 23 patients (39.1%) were diagnosed with obesity, and seven
      patients each (30.4%) were diagnosed with arrhythmia or smoking history. In
      total, only two patients (8.7%) had no association with any of the risk factors
      for ischemic stroke. CONCLUSION: Our results show that a comparatively high
      frequency of ischemic stroke occurs in patients with alcohol-induced liver
      cirrhosis and in patients with a less compromised liver function. In addition, it
      was found that most patients possessed at least one risk factor of ischemic
      stroke.

PMID- 25599785
TI  - Effects of mannose-binding lectin and mannose-binding lectin polymorphisms on
      treatment response in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: The natural course and clinical outcome of hepatitis C virus
      (HCV) infection is related to the interaction between HCV and the immune response
      of the host. Only a limited number of studies have investigated the role of
      mannose-binding lectin (MBL) levels in HCV infection. The aim of the present
      study was to explore the relationship between MBL levels and gene polymorphisms
      on treatment response in patients with chronic hepatitis C (CHC). MATERIALS AND
      METHODS: Serum MBL levels from 50 CHC patients who completed treatment at least
      24 weeks before the present study and 75 healthy HCV-negative controls were
      measured. In addition, the presence of codon 54 mutations was investigated.
      Correlational analyses were performed to determine relationships between MBL
      levels and treatment response. RESULTS: In patients, mean serum MBL levels were
      lower and the rate of codon 54 mutations was higher. However, these differences
      were not statically significant. In both patients and controls, serum MBL levels
      were significantly lower in individuals with codon 54 mutations. Moreover, serum
      MBL levels and the rate of the codon 54 mutation were similar in patients
      regardless of treatment response. CONCLUSION: Our findings suggest that low MBL
      levels do not increase the susceptibility for HCV infection. Furthermore, MBL
      levels were not found to have a significant effect on the course of the disease
      or treatment response.

PMID- 25599786
TI  - Outcomes and predictors of in-hospital mortality among cirrhotic patients with
      non-variceal upper gastrointestinal bleeding in upper Egypt.
AB  - BACKGROUND/AIMS: Variceal bleeding is one of the most frequent causes of
      morbidity and mortality among cirrhotic patients. Clinical endoscopic features
      and outcomes of cirrhotic patients with non-variceal upper gastrointestinal
      bleeding (NVUGIB) have been rarely reported. Our aim is to identify treatment
      outcomes and predictors of in-hospital mortality among cirrhotic patients with
      non-variceal bleeding in Upper Egypt. MATERIALS AND METHODS: A prospective study
      of 93 cirrhotic patients with NVUGIB who were admitted to the Tropical Medicine
      and Gastroenterology Department, Assiut University Hospital (Assiut, Egypt) over
      a one-year period (November 2011 to October 2012). Clinical features, endoscopic
      findings, clinical outcomes, and in-hospital mortality rates were studied.
      Patient mortality during hospital stay was reported. Many independent risk
      factors of mortality were evaluated by means of univariate and multiple logistic
      regression analyses. RESULTS: Of 93 patients, 65.6% were male with a mean age of
      53.3 years. The most frequent cause of bleeding was duodenal ulceration (26.9%).
      Endoscopic treatment was needed in 45.2% of patients, rebleeding occurred in
      4.3%, and the in-hospital mortality was 14%. Hypovolemic shock was the most
      common cause of death (46.2%). Independent risk factors of in-hospital mortality
      among cirrhotic patients with NVUGIB in our study were bacterial infection during
      hospitalization [odds ratio (OR) =0.32, 95% confidence interval (CI) =0.03-0.89],
      shock (OR =1.12, 95% CI =0.68-1.54), early rebleeding (OR =2.26, 95% CI =1.85
      3.21), low serum albumin (OR =3.81, 95% CI =2.35-4.67), low baseline hemoglobin
      (OR =0.714, 95% CI =0.32-1.24), and the need for endoscopic treatment (OR =2.96,
      95% CI =0.62-3.63). CONCLUSION: Bacterial infection during hospitalization,
      shock, early rebleeding, low serum albumin, low baseline hemoglobin, and the need
      for endoscopic treatment were independent risk factors of in-hospital mortality
      among cirrhotic patients with NVUGIB in Upper Egypt.

PMID- 25599787
TI  - New hormones to predict the severity of gallstone-induced acute pancreatitis.
AB  - BACKGROUND/AIMS: Levels of the hormones ghrelin and leptin in rat models of acute
      pancreatitis (AP) have been investigated in several experimental studies.
      However, there are very few clinical studies addressing the connection between
      hormone levels and AP. A few recent studies investigating the changes in ghrelin
      and leptin levels in patients with AP have been reported; however, our study is
      the first clinical study to investigate the change of nesfatin-1 levels in
      patients with gallstone-induced AP. MATERIALS AND METHODS: Forty patients were
      enrolled in this study, eight of which presented with severe AP. Two blood
      samples were obtained from each study patient. The first blood samples were
      obtained at patient admission to the hospital and the second was obtained at
      patient discharge. All samples were collected after at least 6 h of fasting.
      Plasma nesfatin-1, leptin, and ghrelin levels were measured. RESULTS: In all 40
      patients, nesfatin-1 and leptin levels were higher at admission and had decreased
      at discharge. In contrast, the ghrelin levels at discharge were significantly
      higher than those at admission. Only the changes in these hormones in the mild AP
      group were significant. CONCLUSION: Levels of these hormones were altered during
      the course of gallstone-induced AP. These changes might be associated with the
      clinical outcomes of the disease. To clarify whether the magnitude of the change
      in hormone levels at AP onset can be used as a biomarkers to predict the severity
      of the disease requires further investigation.

PMID- 25599788
TI  - The Nutritional Risk Screening 2002 tool for detecting malnutrition risk in
      hospitalised patients: perspective from a developing country.
AB  - BACKGROUND/AIMS: To verify the validity of the Nutritional Risk Screening (NRS)
      2002 test in a Turkish population. MATERIALS AND METHODS: We prospectively
      investigated 2566 patients at a tertiary referral hospital. Nutritional status
      was screened using NRS 2002, and the length of the stay (LOS) was the main
      outcome measure. Hospital stays >10 days were accepted as prolonged LOS. NRS
      scores >=3 were accepted as indicating risk for malnutrition. Statistical
      analyses were performed to determine the independent risk factors for
      malnutrition risk and prolonged LOS. RESULTS: The mean age of patients was 56.6+/
      16.9 years. According to the NRS 2002, 964 patients (37.6%) were without risk,
      1320 (51.4%) warranted surveillance and 282 (11%) were at high risk for
      malnutrition. Malnutrition rate was the highest in the intensive care unit
      (22.01%). Prolonged LOS was seen in 24.4% of patients. Intensive care unit stay
      [odds ratio (OR): 0.585; confidence interval (CI): 1.45-2.22; p<0.001] and an NRS
      score >=3 (OR: 0.88; CI: 1.87-3.13; p<0.001) were independent risk factors for
      prolonged LOS. CONCLUSION: Improving healthcare outcomes while avoiding
      preventable healthcare costs is an important goal of healthcare provision in
      developing countries. NRS 2002 was predictive of LOS, and thus, of patient
      prognosis. Further community-based studies are warranted to assess the impact of
      NRS 2002 on reducing healthcare costs.

PMID- 25599789
TI  - Report of seven children with hepatopulmonary syndrome.
AB  - Hepatopulmonary syndrome is an important pulmonary vascular complication of liver
      disease. Its diagnosis is based on the presence of hypoxaemia and the
      demonstration of intrapulmonary shunting by contrast-enhanced echocardiography or
      perfusion lung scanning. Awareness of this condition is critical to improve the
      outcomes of patients with chronic liver disease and/or portal hypertension
      because hepatopulmonary syndrome receives additional priority on the waiting list
      for transplantation. A non-invasive measurement of the blood oxygen saturation
      with pulse oximetry is recommended as a screening tool for this syndrome. The aim
      of this report was to present clinical and laboratory findings and follow-up of
      seven paediatric patients who were diagnosed with HPS at our centre. 

PMID- 25599790
TI  - A case of uneventful ABO-incompatible liver transplantation from a deceased donor
      managed with routine immunosuppressive treatment.
AB  - ABO-incompatible liver transplantation (ILT) was formerly contraindicated because
      of the increased risk of antibody-mediated humoral graft rejection due to
      preformed anti-A/-B antibodies on recipient endothelial cells. A 2.5-year-old
      girl with end-stage liver disease underwent cadaveric donation ILT because of
      acute liver failure and esophageal variceal bleeding before transplantation. The
      patient's blood type was A Rh (-) and the donor's blood type B Rh (+). The
      operation and postoperative course were uneventful. The immunosuppression
      consisted of steroids, and tacrolimus was initiated on the day of the surgery.
      The patient's hemoglobin level did not change, and direct Coombs test performed
      daily was consistently negative. Anti-B titer was observed at a maximum of 1/8.
      The patient was followed up during the first year. This case of ILT from a
      cadaveric donor is significant because the 2.5-year-old recipient did not
      experience any complications after undergoing routine immunosuppressive
      treatment. 

PMID- 25599791
TI  - Conservative management of spontaneous retroperitoneal bleeding after severe
      coughing.

PMID- 25599792
TI  - Uncommon presentation: primary gastric actinomycosis.

PMID- 25599793
TI  - Foreign body in liver: sewing needle.

PMID- 25599794
TI  - Abdominal pain developing from a polyarteritis nodosa-induced hepatic aneurysm.

PMID- 25599795
TI  - Celiac disease and iron deficiency anemia.

PMID- 25599796
TI  - Inflammatory pseudotumor: inaccurate histopathological documentation.

PMID- 25599797
TI  - The impact of prior antibiotic use on blood culture and antibiotic susceptibility
      results in patients with biliary obstruction.

PMID- 25599798
TI  - Comment on long-term results of nonoperative treatment for uncomplicated acute
      appendicitis.

PMID- 25599799
TI  - "If a fake friend stays in your vodkabulary as a stem friend": granulocyte colony
      stimulating factor promoted stem cell therapy in severe alcoholic hepatitis.

PMID- 25599800
TI  - Neotropical fish-fruit interactions: eco-evolutionary dynamics and conservation.
AB  - Frugivorous fish play a prominent role in seed dispersal and reproductive
      dynamics of plant communities in riparian and floodplain habitats of tropical
      regions worldwide. In Neotropical wetlands, many plant species have fleshy fruits
      and synchronize their fruiting with the flood season, when fruit-eating fish
      forage in forest and savannahs for periods of up to 7 months. We conducted a
      comprehensive analysis to examine the evolutionary origin of fish-fruit
      interactions, describe fruit traits associated with seed dispersal and seed
      predation, and assess the influence of fish size on the effectiveness of seed
      dispersal by fish (ichthyochory). To date, 62 studies have documented 566 species
      of fruits and seeds from 82 plant families in the diets of 69 Neotropical fish
      species. Fish interactions with flowering plants are likely to be as old as 70
      million years in the Neotropics, pre-dating most modern bird-fruit and mammal
      fruit interactions, and contributing to long-distance seed dispersal and possibly
      the radiation of early angiosperms. Ichthyochory occurs across the angiosperm
      phylogeny, and is more frequent among advanced eudicots. Numerous fish species
      are capable of dispersing small seeds, but only a limited number of species can
      disperse large seeds. The size of dispersed seeds and the probability of seed
      dispersal both increase with fish size. Large-bodied species are the most
      effective seed dispersal agents and remain the primary target of fishing
      activities in the Neotropics. Thus, conservation efforts should focus on these
      species to ensure continuity of plant recruitment dynamics and maintenance of
      plant diversity in riparian and floodplain ecosystems. 

PMID- 25599801
TI  - Laparoscopic pyeloplasty for secondary ureteropelvic junction obstruction: long
      term results.
AB  - OBJECTIVE: To evaluate the long-term results of laparoscopic pyeloplasty in
      patients with secondary ureteropelvic junction obstruction after failed primary
      interventions. METHODS: Between August 2000 and October 2012, transperitoneal
      dismembered laparoscopic pyeloplasty was carried out in 13 patients with a
      surgical history of failed prior surgical interventions. Perioperative outcomes
      as well as long-term results were assessed. These outcomes were compared with
      those of the same procedure carried out for primary ureteropelvic junction
      obstruction by a single surgeon during the same study period. RESULTS:
      Laparoscopic transperitoneal pyeloplasty was completed successfully in all cases
      without converting to open surgery or requiring blood transfusion. The
      preoperative symptoms in 12 of 13 patients all disappeared soon after the
      operation. Asymptomatic severe hydronephrosis found in a 2-year-old boy reduced
      in size postoperatively. When comparing the primary with the secondary
      laparoscopic pyeloplasty carried out by the same surgeon, the mean operative time
      was longer (183 vs 241 min, P = 0.002), estimated blood loss was larger (33 vs 66
      mL, P = 0.03) and the complication rate was higher (8.8% vs 22.2%, P = 0.01) in
      the secondary group. Success rates were 97.9% and 100% (P = 0.41) at a mean
      follow up of 25.9 and 40.0 months (P = 0.14) for the primary and secondary
      groups, respectively. CONCLUSIONS: Laparoscopic pyeloplasty is an excellent
      option for patients who failed previous surgical management. This approach
      provides durable long-term outcomes comparable with those of primary treatment
      for ureteropelvic junction obstruction.

PMID- 25599802
TI  - Clinical characteristics of Scottie Cramp in 31 cases.
AB  - OBJECTIVE: To report the clinical features, with response to therapy and long
      term outcome of Scottie Cramp as described by owners. METHODS: Owners of affected
      dogs provided a description of clinical signs, age of onset and disease
      progression. Medical records, pedigrees and videotapes of cramp episodes were
      evaluated. RESULTS: Thirty-one dogs were recruited; 19 showed generalised
      spasticity and 12 exhibited only hind limb spasticity and skipping. Episodes were
      noted in the first year of life in 76% of dogs and were triggered by excitement,
      stress and exercise. Episode frequency and severity decreased over time with
      behaviour modification and decreased exposure to triggers playing a role in their
      development. One dog was euthanased because of severe refractory signs.
      Fluoxetine reduced the frequency and duration of episodes in seven dogs, but not
      in one severely affected dog. Female dogs were over-represented with only eight
      affected males in the study cohort, and the presence of dogs with cerebellar
      degeneration in the same pedigrees may suggest a more complex mode of inheritance
      than previously reported. CLINICAL SIGNIFICANCE: The disorder recognised as
      Scottie Cramp by dog owners includes dogs with hind limb spasticity in addition
      to generalised cramping. Signs usually improve over time without specific
      treatment.

PMID- 25599804
TI  - Effect of B site coordination environment in the ORR activity in disordered
      brownmillerites Ba2In2-xCexO5+delta.
AB  - Ba2In2O5 brownmillerites in which the In site is progressively doped with Ce
      exhibit excellent oxygen reduction activity under alkaline conditions. Ce doping
      leads to structural changes advantageous for the reaction. Twenty-five percent
      doping retains the ordered structure of brownmillerite with alternate layers of
      tetrahedra and octahedra, whereas further increase in Ce concentration creates
      disorder. Structures with disordered oxygen atoms/vacancies are found to be
      better oxygen reduction reaction catalysts probably aided by isotropic ionic
      conduction, and Ba2In0.5Ce1.5O5+delta is the most active. This enhanced activity
      is correlated to the more symmetric Ce site coordination environment in this
      compound. Stoichiometric perovskite BaCeO3 with the highest concentration of Ce
      shows very poor activity emphasizing the importance of oxygen vacancies, which
      facilitate O2 adsorption, in tandem with catalytic sites in oxygen reduction
      reactions. 

PMID- 25599805
TI  - Corrigendum to: Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle
      Strength During Resistance Training in Men.
AB  - [This corrects the article on p. 441 in vol. 18, PMID: 25352765.]. 

PMID- 25599803
TI  - Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after
      reversal of hypertension in porcine renovascular disease.
AB  - INTRODUCTION: Percutaneous transluminal renal angioplasty (PTRA) fails to fully
      improve cardiac injury and dysfunction in patients with renovascular hypertension
      (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential
      for attenuating cardiac injury after reversal of RVH has not been explored. We
      hypothesized that replenishment of MSCs during PTRA would improve cardiac
      function and oxygenation, and decrease myocardial injury in porcine RVH. METHODS:
      Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA
      with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls.
      Cardiac structure, function (fast-computed tomography (CT)), and myocardial
      oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were
      assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial
      injury were evaluated ex-vivo. Kidney venous and systemic blood levels of
      inflammatory markers were measured and their renal release calculated. RESULTS:
      PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate,
      similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated
      pigs. PTRA attenuated left ventricular remodeling, whereas myocardial
      oxygenation, subendocardial microvascular density, and diastolic function
      remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating
      isoprostane levels and renal release of inflammatory cytokines increased in RVH
      and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative
      stress, inflammation, collagen deposition, and fibrosis. CONCLUSIONS: Intra-renal
      MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic
      oxidative stress and inflammation, and thereby improved cardiac function,
      oxygenation, and myocardial injury four weeks after revascularization, suggesting
      a therapeutic potential for adjunctive MSC delivery to preserve cardiac function
      and structure after reversal of experimental RVH.

PMID- 25599807
TI  - "Motionyms": activity-related musculoskeletal and medical problems (or "not an
      eponym!!").
AB  - Many common conditions in sports medicine are eponymous; that is, they are named
      for the person first describing or popularizing the diagnosis. But other medical
      conditions are named for the action or activity that is associated with the
      pathology. This article lists and references these conditions, and suggests that
      this group of conditions should be called "motionyms".

PMID- 25599806
TI  - Electrocardiographic intervals in foetuses with CHD.
AB  - OBJECTIVES: To assess foetal electrocardiographic intervals across gestational
      age among foetuses with and without congenital heart disease, and to investigate
      differences between groups. DESIGN: A prospective observational cohort study.
      SETTING: Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of
      New York-Presbyterian. Population or sample A total of 92 participants with
      singleton pregnancies, 41 with normal anatomy and 51 with congenital heart
      disease were included in this study. METHODS: Using a maternal abdominal monitor,
      foetal electrocardiogram was obtained serially from foetuses with and without
      congenital heart disease at 20-24 weeks (F1), 28-32 weeks (F2), and 34-38 weeks
      (F3) of gestation. A signal-averaged waveform was calculated, and PR, QRS, and QT
      intervals were measured. Intervals from controls were compared with gestational
      age norms. Using Pearson's correlation coefficient, we analysed the relationship
      between gestational age and foetal electrocardiographic intervals. Intervals from
      control and congenital heart disease foetuses were compared by Student's t-test.
      RESULTS: PR (r=0.333, p=0.02) and QRS (r=0.248, p=0.05) intervals correlated with
      gestational age only among controls. QRS intervals in foetuses with congenital
      heart disease were significantly longer than controls at F1 (63 +/- 6 versus 52
      +/- 5 ms, p<0.001), F2 (61 +/- 8 versus 56 +/- 7 ms, p=0.02), and F3 (64 +/- 10
      versus 56 +/- 9 ms, p=0.007). CONCLUSIONS: PR and QRS intervals lengthen across
      gestational age among foetuses with normal cardiac anatomy but not in foetuses
      with congenital heart diseases. As early as 20 weeks of gestation, differences
      between foetuses with and without congenital heart disease are discernible, with
      congenital heart disease foetuses demonstrating longer QRS intervals compared
      with controls.

PMID- 25599808
TI  - Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary
      tuberculosis when testing non-respiratory samples: a systematic review.
AB  - BACKGROUND: Although the evidence base regarding the use of the Xpert MTB/RIF
      assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory
      samples is well established, the evidence base for its diagnostic accuracy for
      extrapulmonary and sputum-scarce pulmonary TB when testing non-respiratory
      samples is less clearly defined. METHODS: A systematic literature search of 7
      electronic databases (Medline, EMBASE, ISI Web of Science, BIOSIS, Global Health
      Database, Scopus and Cochrane Database) was conducted to identify studies of the
      diagnostic accuracy of the Xpert assay when testing non-respiratory samples
      compared with a culture-based reference standard. Data were extracted and study
      quality was assessed using the QUADAS-2 tool. Sensitivities and specificities
      were calculated on a per-sample basis, stratified by sample type and smear
      microscopy status and summarised using forest plots. Pooled estimates were
      calculated for groups with sufficient data. RESULTS: Twenty-seven studies with a
      total of 6,026 non-respiratory samples were included. Among the 23 studies
      comparing Xpert and culture done on the same samples, sensitivity was very
      heterogeneous with a median sensitivity of 0.83 (IQR, 0.68-0.94) whereas
      specificities were typically very high (median, 0.98; IQR, 0.89-1.00). The pooled
      summary estimates of sensitivity when testing smear-positive and smear-negative
      samples were 0.95 (95% CI 0.91-1.00) and 0.69 (95% CI 0.60-0.80), respectively.
      Pooled summary estimates of sensitivity varied substantially between sample
      types: lymph node tissue, 0.96 (95% CI, 0.72-0.99); tissue samples of all types,
      0.88 (95% CI, 0.76-0.94); pleural fluid, 0.34 (95% CI, 0.24-0.44); gastric
      aspirates for diagnosis of sputum-scarce pulmonary TB, 0.78 (IQR, 0.68 - 0.85).
      Median sensitivities when testing cerebrospinal fluid and non-pleural serous
      fluid samples were 0.85 (IQR, 0.75-1.00) and 0.67 (IQR, 0.00-1.00), respectively.
      CONCLUSION: Xpert detects with high specificity the vast majority of EPTB cases
      with smear-positive non-respiratory samples and approximately two-thirds of those
      with smear-negative samples. Xpert is a useful rule-in diagnostic test for EPTB,
      especially when testing cerebrospinal fluid and tissue samples. In addition, it
      has a high sensitivity for detecting pulmonary TB when using gastric aspirate
      samples. These findings support recent WHO guidelines regarding the use of Xpert
      for TB diagnosis from non-respiratory samples.

PMID- 25599810
TI  - Erratum: RE: An Unusual Course of Sinoatrial Node Artery Originating from Distal
      Right Coronary Artery.
AB  - [This corrects the article on p. 878 in vol. 15, PMID: 25469103.]. 

PMID- 25599809
TI  - Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary
      disease.
AB  - INTRODUCTION: The p38 protein kinases, in particular p38alpha and p38beta,
      regulate the production of multiple inflammatory mediators. Consequentially,
      considerable effort has been focused on trying to develop p38 inhibitors for the
      treatment of inflammatory diseases. Some 20 p38 inhibitors have progressed to
      clinical development, mostly for the treatment of rheumatoid arthritis, but with
      little success. Increasingly, interest has turned to their use in other
      indications and notably chronic obstructive pulmonary disease (COPD). AREAS
      COVERED: In this review, the author discusses the eight p38 inhibitors that have
      been clinically evaluated. Acumapimod is the only one of four orally delivered
      inhibitors that remains in active development while Phase II results of PH-797804
      and losmapimod are compared. The activity of two inhibitors designed for inhaled
      delivery, RV-568 and PF-03715455, is compared but little is known about AZD-7624
      or the discontinued GSK-610677. EXPERT OPINION: Results from animal models
      provide a clear rationale for developing p38 inhibitors for COPD, and appear to
      be (partially) validated by the efficacy seen with PH-797804 and losmapimod.
      Inhaled delivery provides the opportunity to enhance p38 inhibition in the lung
      while reducing unwanted systemic effects of p38 inhibition. Validation of this
      hypothesis should come from the results of the recently completed Phase II study
      with RV-568.

PMID- 25599812
TI  - Evaluation of the diffusive gradients in thin films technique using a mixed
      binding gel for measuring iron, phosphorus and arsenic in the environment.
AB  - Simultaneous measurements of dissolved iron (Fe), phosphorus (P), and arsenic
      (As) were made using the diffusive gradients in thin films technique equipped
      with a mixed binding gel impregnated with zirconium oxide and Chelex-100 (ZrO
      Chelex DGT). The ZrO-Chelex binding gel exhibited rapid binding dynamics to
      Fe(II), P(PO4(3-)), and As(III)/As(V) in mixed solutions of the three elements.
      The bound Fe, P, and As could be quantitatively recovered using an established
      four-step elution procedure. Simultaneous measurements of the three elements with
      ZrO-Chelex DGT were validated through time-series experiments, and there was no
      influence of pH (4.1 to 7.1) and ionic strength (0.01 to 800 mM). The DGT
      capacities for As(III) and As(V) were 69.0 MUg and 186 MUg per device,
      respectively, which were much greater than those of the widely used ferrihydrite
      DGT. Applications in synthesized freshwaters and in sediments further confirmed
      its feasibility in simultaneous measurements in the environment. The present
      study offered that the ZrO-Chelex DGT will be a useful tool in in situ monitoring
      of Fe-P-As and assessment of their interactions in the biogeochemical processes.

PMID- 25599813
TI  - Energy efficiency in surmounting the central energy barrier: a quantum dynamics
      study of the OH + CH3 -> O + CH4 reaction.
AB  - The present quantum dynamics study of the OH + CH3 shows that, for this "central"
      (slightly early) barrier reaction, it is the vibrational energy of the reactant
      OH that is more effective in promoting the reactivity than the translational
      energy; while previous studies show that, for its forward reaction O + CH4 also
      with a "central" (slightly late) barrier, it is the translational energy that is
      more effective in surmounting the energy barrier than the vibrational energy.
      Since both barriers deviate only slightly from the center of the potential energy
      surface, these findings indicate that for these two reactions with more-or-less
      central barriers, a small change of the barrier location can greatly affect which
      energy form determines the reaction reactivity. This study also shows that both
      the rotational excitation states of OH and CH3 hinder the reactivity. 

PMID- 25599815
TI  - Feasibility of novel (H3C)nX(SiH3)3-n compounds (X = B, Al, Ga, In): structure,
      stability, reactivity, and Raman characterization from ab initio calculations.
AB  - We employ ab initio calculations to predict the equilibrium structure, stability,
      reactivity, and Raman scattering properties of sixteen different (H3C)nX(SiH3)3-n
      compounds (X = B, Al, Ga, In) with n = 0-3. Among this methylsilylmetal family,
      only the (H3C)3X members, i.e., trimethylboron (TMB), trimethylaluminum (TMA),
      trimethylgallium (TMG), and trimethylindium (TMI), are currently well-studied.
      The remaining twelve compounds proposed here open up a two-dimensional array of
      new possibilities for precursors in various deposition processes, and evoke
      potential applications in the chemical synthesis of other compounds. We infer
      that within the (H3C)nX(SiH3)3-n family, the compounds with fewer silyl groups
      (and consequently with more methyl groups) are less reactive and more stable.
      This trend is verified from the calculated cohesive energy, Gibbs free energy of
      formation, bond strength, and global chemical indices. Furthermore, we propose
      sequential reaction routes for the synthesis of (H3C)nX(SiH3)3-n by substitution
      of methyl by silyl groups, where the silicon source is the silane gas. The
      corresponding reaction barriers for these chemical transformations lie in the
      usual energy range typical for MOCVD processes. We also report the Raman spectra
      and light scattering properties of the newly proposed (H3C)nX(SiH3)3-n compounds,
      in comparison with available data of known members of this family. Thus, our
      computational experiment provides useful information for a systematic
      understanding of the stability/reactivity and for the identification of these
      compounds. 

PMID- 25599816
TI  - Perspective: Peripheral nerve stimulation and peripheral nerve field stimulation
      birds of a different feather.

PMID- 25599811
TI  - Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and
      management.
AB  - BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal
      dominant genetic disease, with an estimated prevalence of one case per 125,000
      live births. RSTS is characterized by typical facial features, microcephaly,
      broad thumbs and first toes, intellectual disability, and postnatal growth
      retardation. However, no standard diagnostic criteria are available for RSTS. In
      this review, we summarized the clinical features and genetic basis of RSTS and
      highlighted areas for future studies on an appropriate diagnostic protocol and
      follow-up care for RSTS. DISCUSSION: RSTS is primarily characterized by delayed
      growth in height and weight, microcephaly, dysmorphic facial features, and broad
      thumbs and big toe. Over 90% RSTS individuals with disabilities survive to
      adulthood, but healthcare for these patients is particularly complex, time
      consuming, and costly. In addition, no standard diagnostic criteria and follow-up
      care guidelines are available for RSTS. It has been shown that mutations in the
      genes encoding the cyclic-AMP-regulated enhancer binding protein (CREBBP) and the
      E1A-binding protein p300 (EP300) contributed to the development of RSTS.
      Therefore, genetic tests are useful for the diagnosis of RSTS, although most RSTS
      cases are currently diagnosed based on clinical features. The clinical features
      of RSTS have been extensively studied, which significantly contributes to the
      diagnosis of this extremely rare syndrome. However, the pathogenesis and genotype
      phenotype associations of RSTS are largely unknown. Therefore, multicenter
      studies and international cooperation are highlighted for better understanding of
      this disease, establishing standard diagnostic criteria, and providing
      professional management and follow-up care of RSTS.

PMID- 25599817
TI  - Incorporation of personal single nucleotide polymorphism (SNP) data into a
      national level electronic health record for disease risk assessment, part 2: the
      incorporation of SNP into the national health information system of Turkey.
AB  - BACKGROUND: A personalized medicine approach provides opportunities for
      predictive and preventive medicine. Using genomic, clinical, environmental, and
      behavioral data, the tracking and management of individual wellness is possible.
      A prolific way to carry this personalized approach into routine practices can be
      accomplished by integrating clinical interpretations of genomic variations into
      electronic medical record (EMR)s/electronic health record (EHR)s systems. Today,
      various central EHR infrastructures have been constituted in many countries of
      the world, including Turkey. OBJECTIVE: As an initial attempt to develop a
      sophisticated infrastructure, we have concentrated on incorporating the personal
      single nucleotide polymorphism (SNP) data into the National Health Information
      System of Turkey (NHIS-T) for disease risk assessment, and evaluated the
      performance of various predictive models for prostate cancer cases. We present
      our work as a miniseries containing three parts: (1) an overview of requirements,
      (2) the incorporation of SNP into the NHIS-T, and (3) an evaluation of SNP data
      incorporated into the NHIS-T for prostate cancer. METHODS: For the second article
      of this miniseries, we have analyzed the existing NHIS-T and proposed the
      possible extensional architectures. In light of the literature survey and
      characteristics of NHIS-T, we have proposed and argued opportunities and
      obstacles for a SNP incorporated NHIS-T. A prototype with complementary
      capabilities (knowledge base and end-user applications) for these architectures
      has been designed and developed. RESULTS: In the proposed architectures, the
      clinically relevant personal SNP (CR-SNP) and clinicogenomic associations are
      shared between central repositories and end-users via the NHIS-T infrastructure.
      To produce these files, we need to develop a national level clinicogenomic
      knowledge base. Regarding clinicogenomic decision support, we planned to complete
      interpretation of these associations on the end-user applications. This approach
      gives us the flexibility to add/update envirobehavioral parameters and family
      health history that will be monitored or collected by end users. CONCLUSIONS: Our
      results emphasized that even though the existing NHIS-T messaging infrastructure
      supports the integration of SNP data and clinicogenomic association, it is
      critical to develop a national level, accredited knowledge base and better end
      user systems for the interpretation of genomic, clinical, and envirobehavioral
      parameters.

PMID- 25599819
TI  - Predictors of Colorectal Cancer Screening: Does Rurality Play a Role?
AB  - PURPOSE: The purpose of this study was to explore the associations between
      sociodemographic factors such as residence, health care access, and colorectal
      cancer (CRC) screening among residents of Texas. METHODS: Using the 2012
      Behavioral Risk Factor Surveillance Survey, we performed logistic regression
      analyses to determine predictors of CRC screening among Texas residents,
      including rural versus urban differences. Our outcomes of interest were previous
      (1) CRC screening using any CRC test, (2) fecal occult blood test (FOBT), or (3)
      endoscopy, as well as up-to-date screening using (4) any CRC test, (5) FOBT, or
      (6) endoscopy. The independent variable of interest was rural versus urban
      residence; we controlled for other sociodemographic and health care access
      variables such as lack of health insurance. RESULTS: Multivariate analysis showed
      that individuals who were residents of a rural/non-Metropolitan Statistical Area
      (MSA) location (OR = 0.70, 95% CI = 0.51-0.97) or a suburban county (OR = 0.61,
      95% CI = 0.39-0.95) were less likely to report ever having any CRC screening
      compared to residents of a center city of an MSA. Residents of a rural/non-MSA
      location were less likely (OR = 0.49, 95% CI = 0.28-0.87) than residents of a
      center city of an MSA to be up-to-date using FOBT. There was decreased likelihood
      of ever being screened for CRC among the uninsured (OR = 0.43, 95% CI = 0.31
      0.59). CONCLUSIONS: Effective development and implementation of strategies to
      improve screening rates should aim at improving access to health care, taking
      into account demographic characteristics such as rural versus urban residence.

PMID- 25599818
TI  - Cultural interaction and biological distance in postclassic period Mexico.
AB  - Economic, political, and cultural relationships connected virtually every
      population throughout Mexico during Postclassic period (AD 900-1520). Much of
      what is known about population interaction in prehistoric Mexico is based on
      archaeological or ethnohistoric data. What is unclear, especially for the
      Postclassic period, is how these data correlate with biological population
      structure. We address this by assessing biological (phenotypic) distances among
      28 samples based upon a comparison of dental morphology trait frequencies, which
      serve as a proxy for genetic variation, from 810 individuals. These distances
      were compared with models representing geographic and cultural relationships
      among the same groups. Results of Mantel and partial Mantel matrix correlation
      tests show that shared migration and trade are correlated with biological
      distances, but geographic distance is not. Trade and political interaction are
      also correlated with biological distance when combined in a single matrix. These
      results indicate that trade and political relationships affected population
      structure among Postclassic Mexican populations. We suggest that trade likely
      played a major role in shaping patterns of interaction between populations. This
      study also shows that the biological distance data support the migration
      histories described in ethnohistoric sources.

PMID- 25599820
TI  - Grading acute graft-versus-host disease: time to reconsider.
AB  - Acute graft-versus-host disease (GVHD) is a common and serious complication of
      allogeneic blood and marrow transplantation. Acute GVHD is commonly graded
      according to modified Glucksberg criteria. There is considerable within-grade
      heterogeneity with different patterns of skin, liver, or gut involvement. In this
      commentary, we provide an analytical review of ambiguities in acute GVHD severity
      scoring and offer specific proposals meant to generate discussion in the BMT
      community for adoption, refinement, and where appropriate, validation studies. 

PMID- 25599821
TI  - Dynamic directed interictal connectivity in left and right temporal lobe
      epilepsy.
AB  - OBJECTIVE: There is increasing evidence that epileptic activity involves
      widespread brain networks rather than single sources and that these networks
      contribute to interictal brain dysfunction. We investigated the fast-varying
      behavior of epileptic networks during interictal spikes in right and left
      temporal lobe epilepsy (RTLE and LTLE) at a whole-brain scale using directed
      connectivity. METHODS: In 16 patients, 8 with LTLE and 8 with RTLE, we estimated
      the electrical source activity in 82 cortical regions of interest (ROIs) using
      high-density electroencephalography (EEG), individual head models, and a
      distributed linear inverse solution. A multivariate, time-varying, and frequency
      resolved Granger-causal modeling (weighted Partial Directed Coherence) was
      applied to the source signal of all ROIs. A nonparametric statistical test
      assessed differences between spike and baseline epochs. Connectivity results
      between RTLE and LTLE were compared between RTLE and LTLE and with
      neuropsychological impairments. RESULTS: Ipsilateral anterior temporal structures
      were identified as key drivers for both groups, concordant with the epileptogenic
      zone estimated invasively. We observed an increase in outflow from the key driver
      already before the spike. There were also important temporal and extratemporal
      ipsilateral drivers in both conditions, and contralateral only in RTLE. A
      different network pattern between LTLE and RTLE was found: in RTLE there was a
      much more prominent ipsilateral to contralateral pattern than in LTLE. Half of
      the RTLE patients but none of the LTLE patients had neuropsychological deficits
      consistent with contralateral temporal lobe dysfunction, suggesting a
      relationship between connectivity changes and cognitive deficits. SIGNIFICANCE:
      The different patterns of time-varying connectivity in LTLE and RTLE suggest that
      they are not symmetrical entities, in line with our neuropsychological results.
      The highest outflow region was concordant with invasive validation of the
      epileptogenic zone. This enhanced characterization of dynamic connectivity
      patterns could better explain cognitive deficits and help the management of
      epilepsy surgery candidates.

PMID- 25599822
TI  - Changes in the expression of DNA double strand break repair genes in primordial
      follicles from immature and aged rats.
AB  - Oocytes present at birth undergo a progressive process of apoptosis in humans and
      other mammals as they age. Accepted opinion is that no fresh oocytes are produced
      other than those present at the time of birth. Studies have shown that DNA repair
      genes in oocytes of mice and women decline with age, and lack of these genes show
      higher DNA breaks and increased oocyte death rates. In contrast to the ethical
      problems associated with monitoring the changes in DNA double-strand breaks in
      oocytes from young and old humans, it is relatively easy to carry out such a
      study using a rodent model. In this study, the mRNA levels of DNA repair genes
      are compared with protein products of some of the genes in the primordial
      follicles isolated from immature (18-20 days) and aged (400-450 days) female
      rats. Results revealed a significant decline in mRNA levels of BRAC1 (P < 0.01),
      RAD51 (P < 0.05), ERCC2 (P < 0.05), and H2AX (P < 0.01) of DNA repair genes and
      phospho-protein levels of BRAC1 (P < 0.01) and H2AX (P < 0.05) in primordial
      follicles of aged rats. Impaired DNA repair is confirmed as a mechanism of oocyte
      ageing. 

PMID- 25599823
TI  - The oviduct: a neglected organ due for re-assessment in IVF.
AB  - The oviduct has long been considered a 'pipeline', a tube allowing transit of
      spermatozoa and embryos; this perspective has been reinforced by the success of
      human IVF. Evidence accumulated over several decades, however, indicates that
      embryos can modulate the metabolism of tubal cells in their environment. Human
      IVF culture media is based on formulations that pass mouse embryo assays as
      quality control: the requirements of mouse embryos differ from those of human
      embryos, and therefore conditions for human IVF are far removed from the natural
      environment of the oviduct. The preimplantation environment, both in vitro and in
      vivo, is known to affect the health of offspring through mechanisms that
      influence imprinting. Recent studies also show that male accessory glands act in
      synergy with the oviduct in providing an optimal environment, and this represents
      a further perspective on the oviduct's contribution to harmonious embryo
      development and subsequent long-term health. The metabolism of the human embryo
      is far from being understood, and a 'return' to in-vivo conditions for
      preimplantation development is worthy of consideration. Although results obtained
      in rodents must be interpreted with caution, lessons learned from animal embryo
      culture must not be neglected. 

PMID- 25599824
TI  - Impact of blastocyst biopsy and comprehensive chromosome screening technology on
      preimplantation genetic screening: a systematic review of randomized controlled
      trials.
AB  - Embryonic aneuploidy is highly prevalent in IVF cycles and contributes to
      decreased implantation rates, IVF cycle failure and early pregnancy loss.
      Preimplantation genetic screening (PGS) selects the most competent (euploid)
      embryos for transfer, and has been proposed to improve IVF outcomes. Use of PGS
      with fluorescence-in-situ hybridization technology after day 3 embryo biopsy (PGS
      v1) significantly lowers live birth rates and is not recommended for use.
      Comprehensive chromosome screening technology, which assesses the whole
      chromosome complement, can be achieved using different genetic platforms. Whether
      PGS using comprehensive chromosome screening after blastocyst biopsy (PGS-v2)
      improves IVF outcomes remains to be determined. A systematic review of randomized
      controlled trials was conducted on PGS-v2. Three trials met full inclusion
      criteria, comparing PGS-v2 and routine IVF care. PGS-v2 is associated with higher
      clinical implantation rates, and higher ongoing pregnancy rates when the same
      number of embryos is transferred in both PGS and control groups. Additionally,
      PGS-v2 improves embryo selection in eSET practice, maintaining the same ongoing
      pregnancy rates between PGS and control groups, while sharply decreasing multiple
      pregnancy rates. These results stem from good-prognosis patients undergoing IVF.
      Whether these findings can be extrapolated to poor-prognosis patients with
      decreased ovarian reserve remains to be determined. 

PMID- 25599825
TI  - Nuclear volume differences between balanced and unbalanced spermatozoa in
      chromosomal translocation carriers.
AB  - While chromosomal translocations are usually associated with a normal phenotype,
      they can still cause male infertility as well as recurrent miscarriages and fetal
      malformations related to their transmission in an unbalanced state. The
      distinction between balanced and unbalanced spermatozoa on morphological criteria
      is still unfeasible. However, we previously showed that: i) spermatozoa with an
      unbalanced content have a higher rate of DNA fragmentation; and ii) that density
      gradient centrifugation partially separates balanced from unbalanced sperm cells.
      We hypothesized that a chromosomal imbalance could alter the fine spermatic
      nuclear architecture and consequently the condensation of DNA, thus modifying
      normal sperm density. Spermatic nuclear volumes in four translocation carriers
      were analyzed using confocal microscopy. Secondarily, FISH analysis was used to
      establish the segregation mode of each spermatozoon. We found the average
      spermatic nuclei size to be higher among unbalanced spermatozoa in all patients
      but one. All the unbalanced modes were associated with larger nuclei in two
      patients, while this was the case for the 3:1 mode only in the other two,
      suggesting an abnormal condensation. This could be the first step in elaborating
      a procedure to completely eliminate unbalanced spermatozoa from semen prior to in
      vitro fertilization. 

PMID- 25599826
TI  - Selection for high and low oxygen consumption altered hepatic mitochondrial
      energy efficiency in mice.
AB  - Selection for high (H) and low (L) oxygen consumption (OC) as an indirect
      estimation of maintenance energy requirement was determined. Feed intake and body
      weight were measured and feed conversion ratio (FCR) of 4-8-week-old mice was
      calculated. Respiratory activity of hepatic mitochondria was measured at 12
      weeks. Total feed intake (H: 103.74 g, L: 97.92 g, P < 0.01), daily feed intake
      (H: 3.70 g/day, L: 3.50 g/day, P < 0.01) and FCR (H: 18.79, L: 15.50, P < 0.01)
      were significantly different between lines. The line by sex interaction was
      significant for FCR. No line differences were observed in males; and the FCR of
      the H line was greater than in the L line in females. H line mice had the highest
      hepatic mitochondrial respiratory activity in state 2 (P < 0.01), the highest
      uncoupled respiratory rate of mitochondria in the presence of an uncoupling agent
      (P < 0.001), and the mitochondrial proton leak. The adenosine diphosphate/ O
      ratio was highest in the L line (P < 0.05). This suggests that the selection for
      high and low OC induced differences in basal mitochondrial respiration and basal
      metabolism, resulting in difference in FCR between H and L lines.

PMID- 25599827
TI  - Circadian timing of metabolism in animal models and humans.
AB  - Most living beings, including humans, must adapt to rhythmically occurring daily
      changes in their environment that are generated by the Earth's rotation. In the
      course of evolution, these organisms have acquired an internal circadian timing
      system that can anticipate environmental oscillations and thereby govern their
      rhythmic physiology in a proactive manner. In mammals, the circadian timing
      system coordinates virtually all physiological processes encompassing vigilance
      states, metabolism, endocrine functions and cardiovascular activity. Research
      performed during the past two decades has established that almost every cell in
      the body possesses its own circadian timekeeper. The resulting clock network is
      organized in a hierarchical manner. A master pacemaker, located in the
      suprachiasmatic nucleus (SCN) of the hypothalamus, is synchronized every day to
      the photoperiod. In turn, the SCN determines the phase of the cellular clocks in
      peripheral organs through a wide variety of signalling pathways dependent on
      feeding cycles, body temperature rhythms, oscillating bloodborne signals and, in
      some organs, inputs of the peripheral nervous system. A major purpose of
      circadian clocks in peripheral tissues is the temporal orchestration of key
      metabolic processes, including food processing (metabolism and xenobiotic
      detoxification). Here, we review some recent findings regarding the molecular and
      cellular composition of the circadian timing system and discuss its implications
      for the temporal coordination of metabolism in health and disease. We focus
      primarily on metabolic disorders such as obesity and type 2 diabetes, although
      circadian misalignments (shiftwork or 'social jet lag') have also been associated
      with the aetiology of human malignancies. 

PMID- 25599829
TI  - Creation of fragrant rice by targeted knockout of the OsBADH2 gene using TALEN
      technology.
AB  - Fragrant rice is favoured worldwide because of its agreeable scent. The presence
      of a defective badh2 allele encoding betaine aldehyde dehydrogenase (BADH2)
      results in the synthesis of 2-acetyl-1-pyrroline (2AP), which is a major
      fragrance compound. Here, transcription activator-like effector nucleases
      (TALENs) were engineered to target and disrupt the OsBADH2 gene. Six heterozygous
      mutants (30%) were recovered from 20 transgenic hygromycin-resistant lines.
      Sanger sequencing confirmed that these lines had various indel mutations at the
      TALEN target site. All six transmitted the BADH2 mutations to the T1 generation;
      and four T1 mutant lines tested also efficiently transmitted the mutations to the
      T2 generation. Mutant plants carrying only the desired DNA sequence change but
      not the TALEN transgene were obtained by segregation in the T1 and T2
      generations. The 2AP content of rice grains of the T1 lines with homozygous
      mutations increased from 0 to 0.35-0.75 mg/kg, which was similar to the content
      of a positive control variety harbouring the badh2-E7 mutation. We also
      simultaneously introduced three different pairs of TALENs targeting three
      separate rice genes into rice cells by bombardment and obtained lines with
      mutations in one, two and all three genes. These results indicate that targeted
      mutagenesis using TALENs is a useful approach to creating important agronomic
      traits. 

PMID- 25599828
TI  - Short- and medium-term efficacy of a Web-based computer-tailored nutrition
      education intervention for adults including cognitive and environmental feedback:
      randomized controlled trial.
AB  - BACKGROUND: Web-based, computer-tailored nutrition education interventions can be
      effective in modifying self-reported dietary behaviors. Traditional computer
      tailored programs primarily targeted individual cognitions (knowledge, awareness,
      attitude, self-efficacy). Tailoring on additional variables such as self
      regulation processes and environmental-level factors (the home food environment
      arrangement and perception of availability and prices of healthy food products in
      supermarkets) may improve efficacy and effect sizes (ES) of Web-based computer
      tailored nutrition education interventions. OBJECTIVE: This study evaluated the
      short- and medium-term efficacy and educational differences in efficacy of a
      cognitive and environmental feedback version of a Web-based computer-tailored
      nutrition education intervention on self-reported fruit, vegetable, high-energy
      snack, and saturated fat intake compared to generic nutrition information in the
      total sample and among participants who did not comply with dietary guidelines
      (the risk groups). METHODS: A randomized controlled trial was conducted with a
      basic (tailored intervention targeting individual cognition and self-regulation
      processes; n=456), plus (basic intervention additionally targeting environmental
      level factors; n=459), and control (generic nutrition information; n=434) group.
      Participants were recruited from the general population and randomly assigned to
      a study group. Self-reported fruit, vegetable, high-energy snack, and saturated
      fat intake were assessed at baseline and at 1- (T1) and 4-months (T2)
      postintervention using online questionnaires. Linear mixed model analyses
      examined group differences in change over time. Educational differences were
      examined with group*time*education interaction terms. RESULTS: In the total
      sample, the basic (T1: ES=-0.30; T2: ES=-0.18) and plus intervention groups (T1:
      ES=-0.29; T2: ES=-0.27) had larger decreases in high-energy snack intake than the
      control group. The basic version resulted in a larger decrease in saturated fat
      intake than the control intervention (T1: ES=-0.19; T2: ES=-0.17). In the risk
      groups, the basic version caused larger decreases in fat (T1: ES=-0.28; T2: ES=
      0.28) and high-energy snack intake (T1: ES=-0.34; T2: ES=-0.20) than the control
      intervention. The plus version resulted in a larger increase in fruit (T1:
      ES=0.25; T2: ES=0.37) and a larger decrease in high-energy snack intake (T1: ES=
      0.38; T2: ES=-0.32) than the control intervention. For high-energy snack intake,
      educational differences were found. Stratified analyses showed that the plus
      version was most effective for high-educated participants. CONCLUSIONS: Both
      intervention versions were more effective in improving some of the self-reported
      dietary behaviors than generic nutrition information, especially in the risk
      groups, among both higher- and lower-educated participants. For fruit intake,
      only the plus version was more effective than providing generic nutrition
      information. Although feasible, incorporating environmental-level information is
      time-consuming. Therefore, the basic version may be more feasible for further
      implementation, although inclusion of feedback on the arrangement of the home
      food environment and on availability and prices may be considered for fruit and,
      for high-educated people, for high-energy snack intake. TRIAL REGISTRATION:
      Netherlands Trial Registry NTR3396;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3396 (Archived by
      WebCite at http://www.webcitation.org/6VNZbdL6w).

PMID- 25599830
TI  - Preoperative factors predicting spontaneous clearance of residual stone fragments
      after flexible ureteroscopy.
AB  - OBJECTIVE: To investigate factors predicting spontaneous clearance of residual
      renal fragments after flexible ureteroscopy. METHODS: Among 546 patients who
      underwent lithotripsy with flexible ureteroscopy, 81 had residual renal
      fragments, as determined by kidney-ureter-bladder films on postoperative day 1.
      The final outcome was determined at 3 months after the last flexible ureteroscopy
      session using non-contrast computed tomography. Patient characteristics and
      preoperative factors were analyzed using the unpaired t-test and chi(2)-test.
      Correlations between the possible predictive factors and the spontaneous
      clearance of residual renal fragments after flexible ureteroscopy were analyzed
      using a multivariate logistic regression model with backward selection. RESULTS:
      Non-contrast computed tomography at postoperative month 3 showed that 33 cases
      (40.7%) had spontaneous clearance of residual renal fragments, whereas 48 (59.3%)
      showed non-clearance. Significant differences were found between these cases in
      terms of stone number, stone location, presence of lower pole calculi and
      preoperative stent placement. Multivariate assessment showed that stone number (P
      = 0.004), presence of lower pole calculi (P = 0.021) and presence of
      hydronephrosis (P = 0.024) were independent predictors of the spontaneous
      clearance of residual renal fragments after flexible ureteroscopy. CONCLUSIONS:
      Stone number, presence of lower pole calculi and presence of hydronephrosis are
      independent predictive factors of the spontaneous clearance of residual renal
      fragments after flexible ureteroscopy.

PMID- 25599831
TI  - Fondaparinux in atrial fibrillation - old dog, new tricks?

PMID- 25599832
TI  - Human-wildlife interactions and zoonotic transmission of Echinococcus
      multilocularis.
AB  - The life cycle of the zoonotic cestode Echinococcus multilocularis depends on
      canids (mainly red foxes) as definitive hosts and on their specific predation on
      rodent species (intermediate hosts). Host densities and predation rates are key
      drivers for infection with parasite eggs. We demonstrate that they strongly
      depend on multi-faceted human-wildlife interactions: vaccination against rabies,
      elimination of top predators, and changing attitude towards wildlife (feeding)
      contribute to high fox densities. The absence of large canids, low hunting
      pressure, and positive attitudes towards foxes modify their anti-predator
      response ('landscape of fear'), promoting their tameness, which in turn
      facilitates the colonization of residential areas and modifies parasite
      transmission. Such human factors should be considered in the assessment of any
      intervention and prevention strategy. 

PMID- 25599833
TI  - ZmpTAC12 binds single-stranded nucleic acids and is essential for accumulation of
      the plastid-encoded polymerase complex in maize.
AB  - The plastid-encoded plastid RNA polymerase (PEP) represents the major
      transcription machinery in mature chloroplasts. Proteomic studies identified four
      plastome- and at least ten nuclear-encoded proteins making up this multimeric
      enzyme. Depletion of single subunits is known to result in strongly diminished
      PEP activity causing severe defects in chloroplast biogenesis. Here, we
      characterized one PEP subunit in maize, ZmpTAC12, and investigated the molecular
      basis underlying PEP-deficiency in Zmptac12 mutants. We show that the ZmpTAC12
      gene encodes two different protein isoforms, both of which localize dually in
      chloroplasts and nuclei. Moreover, both variants assemble into the PEP-complex.
      Analysis of PEP-complex assembly in various maize mutants lacking different PEP
      complex components demonstrates that ZmpTAC12, ZmpTAC2, ZmpTAC10 and ZmMurE are
      each required to accumulate a fully assembled PEP-complex. Antibodies to ZmpTAC12
      coimmunoprecipitate a subset of plastid RNAs that are synthesized by PEP
      dependent transcription. Gel mobility shift analyses with recombinant ZmpTAC12
      revealed binding capabilities with ssRNA and ssDNA, but not dsDNA. Collectively
      these data demonstrate that ZmpTAC12 is required for the proper build-up of the
      PEP-complex and that it interacts with single-stranded nucleic acids. 

PMID- 25599834
TI  - Synthesis and biological evaluation of adamantane-based aminophenols as a novel
      class of antiplasmodial agents.
AB  - A series of adamantane based aminophenol derivatives were synthesized and
      evaluated for their antiplasmodial activity in vitro against Plasmodium
      falciparum (Pf_NF54) and resistant strain (Pf_K1). Herein, we report compounds
      resulting from this work that show excellent potency against both strains.
      Additionally, this series displayed excellent cytotoxicity selectivity index
      against THP1 cell line and had acceptable in vitro DMPK properties. 

PMID- 25599835
TI  - Thio- and selenoglycosides as ligands for biomedically relevant lectins: valency
      activity correlations for benzene-based dithiogalactoside clusters and first
      assessment for (di)selenodigalactosides.
AB  - Substitution of the oxygen atom in the glycosidic linkage by a disulfide bond or
      by selenium makes the resulting glycoside resistant to hydrolysis. To clarify the
      consequences for affinity to lectins we prepared benzene-based mono- to trivalent
      dithiogalactosides. Inhibitory capacity increased with valency for a plant toxin,
      the synthetic compounds potently blocking its binding to a lactose-presenting
      matrix and to cells. Human galectins were much less sensitive to the disulfides
      than the toxin. This differential response constitutes a beneficial effect to
      avoid cross-reactivity in vivo. Symmetrical selenodigalactoside and
      diselenodigalactoside were prepared and similarly tested. Both compounds proved
      rather equally bioactive for the toxin, graded activity was measured for human
      galectins. This result directs attention to further studies to relate Se
      dependent alterations in bond angle and length as well as van der Waals radius to
      binding properties of selenoglycosides to biomedically relevant lectins. 

PMID- 25599836
TI  - Multi-parameter optimization of aza-follow-ups to BI 207524, a thumb pocket 1 HCV
      NS5B polymerase inhibitor. Part 2: Impact of lipophilicity on promiscuity and in
      vivo toxicity.
AB  - We describe our efforts to identify analogs of thumb pocket 1 HCV NS5B inhibitor
      1 (aza-analog of BI 207524) with improved plasma to liver partitioning and a
      predicted human half-life consistent with achieving a strong antiviral effect at
      a reasonable dose in HCV-infected patients. Compounds 3 and 7 were identified
      that met these criteria but exhibited off-target promiscuity in an in vitro
      pharmacology screen and in vivo toxicity in rats. High lipophilicity in this
      class was found to correlate with increased probability for promiscuous behavior
      and toxicity. The synthesis of an 8*11 matrix of analogs allowed the
      identification of C3, an inhibitor that displayed comparable potency to 1,
      improved partitioning to the liver and reduced lipophilicity. Although C3
      displayed reduced propensity for in vitro off-target inhibition and the toxicity
      profile in rats was improved, the predicted human half-life of this compound was
      short, resulting in unacceptable dosing requirements to maintain a strong
      antiviral effect in patients. 

PMID- 25599837
TI  - The discovery and optimization of aminooxadiazoles as potent Pim kinase
      inhibitors.
AB  - High levels of Pim expression have been implicated in several hematopoietic and
      solid tumor cancers. These findings suggest that inhibition of Pim signaling by a
      small molecule Pim-1,2 inhibitor could provide patients with therapeutic benefit.
      Herein, we describe our progress towards this goal starting from the highly Pim
      selective indole-thiadiazole compound (1), which was derived from a nonselective
      hit identified in a high throughput screening campaign. Optimization of this
      compound's potency and its pharmacokinetic properties resulted in the discovery
      of compound 29. Cyclopropane 29 was found to exhibit excellent enzymatic potency
      on the Pim-1 and Pim-2 isoforms (Ki values of 0.55nM and 0.28nM, respectively),
      and found to inhibit the phosphorylation of BAD in the Pim-overexpressing KMS-12
      cell line (IC50=150nM). This compound had moderate clearance and bioavailability
      in rat (CL=2.42L/kg/h; %F=24) and exhibited a dose-dependent inhibition of p-BAD
      in KMS-12 tumor pharmacodynamic (PD) model with an EC50 value of 6.74MUM
      (18MUg/mL) when dosed at 10, 30, 100 and 200mg/kg po in mice. 

PMID- 25599838
TI  - Thiol-derivatized minihepcidins retain biological activity.
AB  - Minihepcidins are small peptides that mimic biological activity of the iron
      regulatory hormone hepcidin. Structurally, they contain thiol-free-cysteine
      residue in position 7 which is crucial for their bioactivity. Nonetheless, free
      sulfhydryl group is not desirable in pharmaceutical entities as it may lead to
      dermatological side effects. Moreover free thiol moiety is quite reactive and
      depending on conditions/reagents may be alkylated and/or oxidized giving various
      Cys-derivatives: S-alkyl cysteines, sulfoxides, sulfones, disulfides,
      cysteinesulfinic and cysteic acids. To limit such reactivity and maintain
      bioactivity of minihepcidin(s) we used thiol-protection strategy based on
      activated vinyl thioethers. Novel S-protected analogs of physiologically active
      minihepcidin PR73 were synthesized and tested in vitro showing activity
      comparable to parental molecule. The most active compound, PR73SH was also tested
      in vivo showing activity profile analogous to PR73. Collectively, our findings
      suggest that S-vinyl-derivatization of minihepcidin(s) may be a suitable approach
      in the development of physiologically active agonists of hepcidin. 

PMID- 25599842
TI  - Dementia. Criminality can be an early sign of frontotemporal dementia.

PMID- 25599839
TI  - Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented
      selective kappa opioid receptor agonists.
AB  - Kappa opioid receptor (KOR) is an important mediator of pain signaling and it is
      targeted for the treatment of various pains. Pharmacophore based mining of
      databases led to the identification of 2-aminobenzimidazole derivative as KOR
      agonists with selectivity over the other opioid receptors DOR and MOR. A short
      SAR exploration with the objective of identifying more polar and hence less brain
      penetrant agonists is described herewith. Modeling studies of the recently
      published structures of KOR, DOR and MOR are used to explain the receptor
      selectivity. The synthesis, biological evaluation and SAR of novel benzimidazole
      derivatives as KOR agonists are described. The in vivo proof of principle for
      anti-nociceptive effect with a lead compound from this series is exemplified. 

PMID- 25599843
TI  - Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary
      breast cancer and axillary lymph node metastases as a prognostic factor.
AB  - BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem
      cells, and the expression of ALDH1 may be a prognostic factor of poor clinical
      outcome. The epithelial-mesenchymal transition may produce cells with stem-cell
      like properties promoted by transcription factors. We investigated the expression
      of ALDH1 and transcription factors in both primary and metastatic lesions, and
      prognostic value of them in breast cancer patients with axillary lymph node
      metastasis (ALNM). METHOD: Forty-seven breast cancer patients with ALNM who
      underwent surgery at Okayama University Hospital from 2002 to 2008 were enrolled.
      We retrospectively evaluated the levels of ALDH1 and transcription factors, such
      as Snail, Slug and Twist, in both primary and metastatic lesions by
      immunohistochemistry. RESULTS: In primary lesions, the positive rate of ALDH1,
      Snail, Slug and Twist was 19, 49, 40 and 26%, respectively. In lymph nodes, that
      of ALDH1, Snail, Slug and Twist was 21, 32, 13 and 23%, respectively. The
      expression of ALDH1 or transcription factors alone was not significantly
      associated with a poor prognosis. However, co-expression of ALDH1 and Slug in
      primary lesions was associated with a shorter DFS (P = 0.009). CONCLUSIONS: The
      evaluation of the co-expression of ALDH1 and transcription factors in primary
      lesions may be useful in prognosis of node-positive breast cancers.

PMID- 25599844
TI  - An in vitro liver model on microfluidic device for analysis of capecitabine
      metabolite using mass spectrometer as detector.
AB  - In this work, an in vitro liver model in a microfluidic device to imitate and
      detect prodrug metabolism was developed. A widely used prodrug capecitabine
      (CAP), which needs to be metabolized into active intermediate in the liver and
      then transformed into final effective drug in tumor cells, was selected as a
      model compound. The microfluidic device we exploited consists of a cell co
      culture section, in which HepG2 cells were cultured to represent liver while MCF
      7 cells were used to represent the tumor tissue, and an on-line solid phase
      extraction (SPE) section connecting to the ionization source of the ESI-Q-TOF
      mass spectrometer. The prodrug metabolism was realized and confirmed within this
      in vitro liver model as the intermediate product of the prodrug 5'-deoxy-5
      fluorouridine (DFUR) was successfully detected with MS after the conditioning of
      HepG2 cells, and the anti-tumor effect of the active metabolite was observed
      through cell vitality assays of MCF-7 cells. The limit of detection (LOD) using
      on-chip SPE was at 10nM and semi-quantitative analysis could be realized. This
      system has been proved useful and practical, showing a potential to replace
      conventional drug screening methods. 

PMID- 25599846
TI  - Silicon nanonets for biological sensing applications with enhanced optical
      detection ability.
AB  - Optical sensors based on fluorescence methods are used in numerous areas of
      society, ranging from healthcare to environmental monitoring. But the race to
      elaborate portable and highly sensitive detection systems leads to the huge
      development of nanomaterial-based sensors. Here, we have fabricated a silicon
      nanonet, or silicon nanowire (SiNW) network, -based biosensor for DNA
      hybridization detection by fluorescence microscopy. We demonstrate that by
      leveraging the properties of the SiNWs such as their large specific surface and
      the high aspect ratio, these nanonet sensors have significantly enhanced
      sensitivity and better selectivity compared to plane substrates. The fluorescence
      signal shows an intensity increasing with the SiNW density on the nanonet and for
      the denser nanonets, the detection limit for DNA hybridization is 1 nM. The
      elaborated Si nanonet-based DNA sensors present more than 50% change in
      fluorescence intensity between complementary DNA and 1 base mismatch DNA which
      shows their high selectivity. Finally, we have integrated the Si nanonet-based
      sensor into a DNA chip and we have shown that this selective sensor can be
      reproduced on a large scale area.

PMID- 25599847
TI  - Effective medium theory for anisotropic metamaterials.
AB  - Materials with anisotropic material parameters can be utilized to fabricate many
      fascinating devices, such as hyperlenses, metasolids, and one-way waveguides. In
      this study, we analyze the effects of geometric anisotropy on a two-dimensional
      metamaterial composed of a rectangular array of elliptic cylinders and derive an
      effective medium theory for such a metamaterial. We find that it is possible to
      obtain a closed-form analytical solution for the anisotropic effective medium
      parameters, provided the aspect ratio of the lattice and the eccentricity of the
      elliptic cylinder satisfy certain conditions. The derived effective medium theory
      not only recovers the well-known Maxwell-Garnett results in the quasi-static
      regime, but is also valid beyond the long-wavelength limit, where the wavelength
      in the host medium is comparable to the size of the lattice so that previous
      anisotropic effective medium theories fail. Such an advance greatly broadens the
      applicable realm of the effective medium theory and introduces many possibilities
      in the design of structures with desired anisotropic material characteristics. A
      real sample of a recently theoretically proposed anisotropic medium, with a near
      zero index to control the flux, is achieved using the derived effective medium
      theory, and control of the electromagnetic waves in the sample is clearly
      demonstrated. 

PMID- 25599845
TI  - Protein-inorganic hybrid nanoflowers as ultrasensitive electrochemical
      cytosensing interfaces for evaluation of cell surface sialic acid.
AB  - The identification of biocompatible nanomaterials with high conductivities as
      sensing interfaces is important in developing novel electrochemical cytosensors.
      We prepared a novel protein-inorganic nanomaterial-bovine serum albumin (BSA)
      incorporated Ag nanoflowers with three-dimensional porous architectures, using a
      simple biomimetic method. The BSA-incorporated Ag nanoflowers were modified on a
      glassy carbon electrode (GCE) surface and conjugated with a targeting lectin
      molecule, i.e., Sambucus nigra agglutinin (SNA), for sensing DLD-1 human colon
      cancer cells. The BSA-incorporated Ag nanoflowers were a suitable platform, and
      showed improved cell-immobilization capacity, and good biocompatibility, with
      retention of activity of the immobilized cells. These properties are attributed
      to the large surface area of the porous structure and the natural BSA layer
      acting as a biocompatible support. The attachment of DLD-1 cells to the GCE
      increased the electron-transfer resistance, with a good correlation with the
      logarithm of the concentration from 1.35*10(2) to 1.35*10(7) cells mL(-1), with a
      low detection limit of 40 cells mL(-1). Based on the affinity between SNA and
      sialic acid (SA), the UV-vis absorption spectrum of the one-step reaction between
      SA and acidic ninhydrin indicated that the average number of SA molecules on a
      single living DLD-1 cell surface was approximately 2.16*10(12). This proposed
      cytosensing strategy had good reproducibility, acceptable precision, and high
      specificity for SA-over-expressed cells, indicating that it has potential
      applications for the early monitoring of tumor cells and convenient evaluation of
      SA on living cells.

PMID- 25599848
TI  - Surgical management of pygopagus conjoined twins with spinal bifida.
AB  - PURPOSE: Conjoined twins are a rare complication of 9 monozygotic twins and are
      associated with high perinatal mortality. Pygopagus are one of the rare types of
      conjoined twins with only a handful of cases reported in the literature. We
      present the case of one-and-half month-old male pygopagus conjoined twins, who
      were joined together dorsally in lower lumbar and sacral region and had spina
      bifida and shared a single thecal sac with combined weight of 6.14 kg. Spinal
      cord was separated at the level of the conus followed by duraplasty. They had
      uneventful recovery with normal 15 months follow-up. CONCLUSION: Separation of
      conjoined twins is recommended in where this is feasible with the anticipated
      survival of both or one infant.

PMID- 25599852
TI  - (TFPP)Eu[Pc(OPh)8]Eu[Pc(OPh)8]/CuPc two-component bilayer heterojunction-based
      organic transistors with high ambipolar performance.
AB  - Organic thin film transistor (OTFT) devices fabricated by the solution-based QLS
      technique from a mixed (phthalocyaninato)(porphyrinato) europium complex
      (TFPP)Eu[Pc(OPh)8]Eu[Pc(OPh)8] exhibit air-stable ambipolar performance with
      mobilities of 6.0 * 10(-5) cm(2) V(-1) s(-)1 for holes and 1.4 * 10(-4) cm(2) V(
      1) s(-1) for electrons, respectively. In good contrast, the two-component bilayer
      heterojunction thin film devices constructed by directly growing
      (TFPP)Eu[Pc(OPh)8]Eu[Pc(OPh)8] on vacuum deposited (VCD) CuPc film using solution
      based QLS method were revealed to show unprecedented ambipolar performance with
      carrier mobilities of 0.16 cm(2) V(-1) s(-1) for holes and 0.30 cm(2) V(-1) s(-1)
      for electrons. In addition to the intrinsic role of p-type organic semiconductor,
      the VCD CuPc film on the substrate also acts as a good template that induces
      significant improvement over the molecular ordering of triple-decker compound in
      the film. In particular, it results in the change in the aggregation mode of
      (TFPP)Eu[Pc(OPh)8]Eu[Pc(OPh)8] from J-type in the single-layer film to H-type in
      the bilayer film according to the UV-vis, XRD, and AFM observations. 

PMID- 25599849
TI  - Reliability analysis of the AOSpine thoracolumbar spine injury classification
      system by a worldwide group of naive spinal surgeons.
AB  - PURPOSE: The aims of this study were (1) to demonstrate the AOSpine thoracolumbar
      spine injury classification system can be reliably applied by an international
      group of surgeons and (2) to delineate those injury types which are difficult for
      spine surgeons to classify reliably. METHODS: A previously described
      classification system of thoracolumbar injuries which consists of a morphologic
      classification of the fracture, a grading system for the neurologic status and
      relevant patient-specific modifiers was applied to 25 cases by 100 spinal
      surgeons from across the world twice independently, in grading sessions 1 month
      apart. The results were analyzed for classification reliability using the Kappa
      coefficient (kappa). RESULTS: The overall Kappa coefficient for all cases was
      0.56, which represents moderate reliability. Kappa values describing
      interobserver agreement were 0.80 for type A injuries, 0.68 for type B injuries
      and 0.72 for type C injuries, all representing substantial reliability. The
      lowest level of agreement for specific subtypes was for fracture subtype A4
      (Kappa = 0.19). Intraobserver analysis demonstrated overall average Kappa
      statistic for subtype grading of 0.68 also representing substantial
      reproducibility. CONCLUSION: In a worldwide sample of spinal surgeons without
      previous exposure to the recently described AOSpine Thoracolumbar Spine Injury
      Classification System, we demonstrated moderate interobserver and substantial
      intraobserver reliability. These results suggest that most spine surgeons can
      reliably apply this system to spine trauma patients as or more reliably than
      previously described systems.

PMID- 25599850
TI  - Posterior vertebral column resection in spinal deformity: a systematic review.
AB  - PURPOSE: This study aimed to assess the amount of correction and risk of
      complications of posterior vertebral column resection (PVCR) in the treatment of
      spinal deformity. METHODS: A comprehensive research was conducted in MEDLINE,
      EMBASE and Cochrane Database of Systematic Reviews for published articles about
      PVCR in spinal deformity. Data from these included studies were pooled with the
      help of the Review Manager software from the Cochrane Collaboration and the R
      software. The amount of correction of PVCR was indicated with change of coronal
      and sagittal Cobb angle after operation. Risk of complications was demonstrated
      with prevalence. RESULTS: 7 studies, a total of 390 patients, were included for
      analysis. The average operative time for PVCR was 430 min and the estimated blood
      loss was 2,639 ml. The mean amount of correction by PVCR was 64.1 degrees  in
      scoliosis and 58.9 degrees  in kyphosis, accounting a correction rate of 61.2 and
      63.1 %, respectively. As to coronal and sagittal imbalance, data were limited.
      The overall prevalence of complications of PVCR was 32 % (95 % CI 12-54 %). The
      most common was neurologic complications, estimated to be 8 % (95 % CI 2-16 %).
      And risk of spinal cord injury was 2 % (95 % CI 0-3 %). The revision rate was 6 %
      (95 % CI 1-13 %). Incidence of infection was pooled to be 2 % (95 % CI 1-4 %).
      Complication rate related with implant was 2 % (95 % CI 0-6 %). CONCLUSION: PVCR
      is a powerful surgical procedure for severe spinal deformity. However, it has the
      risk of excessive blood loss and major complications. Decision of PVCR should be
      prudent and the procedure should be performed by an experienced surgical team.

PMID- 25599851
TI  - Skipped versus consecutive pedicle screw constructs for correction of Lenke 1
      curves.
AB  - PURPOSE: Thoracic pedicle screws provide superior curve correction to hook and
      wire constructs in adolescent idiopathic scoliosis, while increasing cost. The
      number of implants required for best correction and outcome has not yet been
      determined. METHODS: We retrospectively reviewed pre- and post-operative
      radiographs and self-reported outcome measures in an age- and curve-matched
      cohort of 40 patients with Lenke I AIS who underwent selective fusions between
      T3/4 and L1. Twenty patients were treated with thoracic pedicle screws at every
      level bilaterally (CON) and 20 patients with screws at every level on the concave
      side and skipped levels on the convex side of the curve (SKP). All patients had a
      minimum 2-year follow-up. Radiographs were assessed for coronal and sagittal
      curvatures, as well as thoracic torsion and vertebral rotation. Health-related
      quality of life was assessed using the SRS-22 instrument. Instrumentation cost
      data were collected for each case. RESULTS: Postoperative follow-up averaged 28
      months for the CON group and 29 months for the SKP group. No statistically
      significant differences were found between groups with respect to age and pre-
      and post-operative radiographic parameters. Both constructs provided acceptable
      correction of the main thoracic curves (66.9 vs. 66.6 %, CON group and SKP group,
      respectively; p = 0.92), and spontaneous correction of the proximal thoracic
      (41.5 vs. 41.1 %; p = 0.92) and thoracolumbar/lumbar curves (54.8 vs. 54.3 %; p =
      0.92). No significant difference was found in postoperative SRS-22 scores (96 vs.
      94.3; p = 0.34). The CON group cost for instrumentation was significantly higher
      than the SKP group ($19,500 vs. $13,300; p = 0.002). There was no statistically
      significant difference in operating room times between groups. CONCLUSION: Both
      construct types provide excellent coronal correction and sagittal balance, with
      no significant differences in radiographic findings or clinical outcomes. A
      significant decrease in cost was found with use of skipped screw constructs.

PMID- 25599853
TI  - Somatic embryogenesis in ferns: a new experimental system.
AB  - KEY MESSAGE: Somatic embryogenesis has never been reported in ferns. The study
      showed that it is much easier to evoke the acquisition and expression of
      embryogenic competence in ferns than in spermatophytes. We discovered that the
      tree fern Cyathea delgadii offers an effective model for the reproducible and
      rapid formation of somatic embryos on hormone-free medium. Our study provides
      cyto-morphological evidence for the single cell origin and development of somatic
      embryos. Somatic embryogenesis (SE) in both primary and secondary explants was
      induced on half-strength micro- and macro-nutrients Murashige and Skoog medium
      without the application of exogenous plant growth regulators, in darkness. The
      early stage of SE was characterized by sequential perpendicular cell divisions of
      an individual epidermal cell of etiolated stipe explant. These resulted in the
      formation of a linear pro-embryo. Later their development resembled that of the
      zygotic embryo. We defined three morphogenetic stages of fern somatic embryo
      development: linear, early and late embryonic leaf stage. The transition from
      somatic embryo to juvenile sporophyte was quick and proceeded without
      interruption caused by dormancy. Following 9 weeks of culture the efficiency of
      somatic embryogenesis reached 12-13 embryos per responding explant. Spontaneous
      formation of somatic embryos and callus production, which improved the
      effectiveness of the process sevenfold in 10-month-long culture, occurred without
      subculturing. The tendency for C. delgadii to propagate by SE in vitro makes this
      species an excellent model for studies relating to asexual embryogenesis and the
      endogenous hormonal regulation of that process and opens new avenues of
      experimentation.

PMID- 25599854
TI  - Phase evolution in single-crystalline LiFePO4 followed by in situ scanning X-ray
      microscopy of a micrometre-sized battery.
AB  - LiFePO4 is one of the most frequently studied positive electrode materials for
      lithium-ion batteries during the last years. Nevertheless, there is still an
      extensive debate on the mechanism of phase transformation. On the one hand this
      is due to the small energetic differences involved and hence the great
      sensitivity with respect to parameters such as size and morphology. On the other
      hand this is due to the lack of in situ observations with appreciable space and
      time resolution. Here we present scanning transmission X-ray microscopy
      measurements following in situ the phase boundary propagation within a LiFePO4
      single crystal along the (010) orientation during electrochemical
      lithiation/delithiation. We follow, on a battery-relevant timescale, the
      evolution of a two-phase-front on a micrometre scale with a lateral resolution of
      30 nm and with minutes of time resolution. The growth pattern is found to be
      dominated by elastic effects rather than being transport-controlled.

PMID- 25599855
TI  - Treatment of neurological disorders by introducing mRNA in vivo using polyplex
      nanomicelles.
AB  - Sensory nerve disorders are difficult to cure completely considering poor nerve
      regeneration capacity and difficulties in accurately targeting neural tissues.
      Administering mRNA is a promising approach for treating neurological disorders
      because mRNA can provide proteins and peptides in their native forms for mature
      non-dividing neural cells, without the need of entering their nuclei. However,
      direct mRNA administration into neural tissues in vivo has been challenging due
      to too unstable manner of mRNA and its strong immunogenicity. Thus, using a
      suitable carrier is essential for effective mRNA administration. For this
      purpose, we established a novel carrier based on the self-assembly of
      polyethylene glycol (PEG)-polyamino acid block copolymer, i.e. polyplex
      nanomicelles. To investigate the feasibility and efficacy of mRNA administration
      for the treatment of sensory nerve disorders, we used a mouse model of
      experimentally induced olfactory dysfunction. Intranasal administration of mRNA
      loaded nanomicelles provided an efficient and sustained protein expression for
      nearly two days in nasal tissues, particularly in the lamina propria which
      contains olfactory nerve fibers, with effectively regulating the immunogenicity
      of mRNA. Consequently, once-daily intranasal administration of brain-derived
      neurotrophic factor (BDNF)-expressing mRNA using polyplex nanomicelles remarkably
      enhanced the neurological recovery of olfactory function along with repairing the
      olfactory epithelium to a nearly normal architecture. To the best of our
      knowledge, this is the first study to show the therapeutic potential of
      introducing exogenous mRNA for the treatment of neurological disorders. These
      results indicate the feasibility and safety of using mRNA, and provide a novel
      strategy of mRNA-based therapy. 

PMID- 25599857
TI  - Revisional Laparoscopic Gastric Pouch Resizing for Inadequate Weight Loss After
      Roux-en-Y Gastric Bypass.
AB  - BACKGROUND: Weight regain due to gastric pouch dilatation after Roux-en-Y gastric
      bypass (RYGB) is seen more frequently after long-term follow-up. We studied the
      feasibility and safety of laparoscopic pouch resizing (LPR) for dilated gastric
      pouch after RYGB associated with inadequate weight loss. METHODS: From 1st June
      2011 to 1st September 2013, patients who underwent LPR after failed RYGB were
      retrospectively compared and analyzed. Data included patient demographics,
      comorbidity, indication for revision, preoperative weight and BMI, operative
      time, hospital stay, conversion rate, mean follow-up, body mass index (BMI) loss,
      percentage excess weight loss (%EWL), reoperation rate, morbidity, and mortality.
      RESULTS: Out of 170 revisional bariatric procedures, 32 LPR (27/5, F/M) were
      performed for dilated gastric pouch after RYGB. The mean age, preoperative
      weight, and BMI were 38.3 +/- 9.3 years, 101.7 +/- 22.8 kg, 38.8 +/- 6.4 kg/m(2),
      respectively. The median operative time and hospital stay were 100 min and 2
      days, respectively. All pouch resizing procedures were carried out
      laparoscopically, with none requiring conversion to open surgery. The overall
      complication and reoperation rates were 15.6 and 3.1 %, respectively. There were
      no deaths. The mean follow-up was 14.1 +/- 6.2 months. The mean postoperative BMI
      was 32.8 +/- 7.3 kg/m(2), and the median %EWL was 29.1 %. CONCLUSIONS: LPR is
      safe and can lead to adequate weight loss. However, long-term follow-up is needed
      to determine the efficiency and durability of this procedure.

PMID- 25599856
TI  - Synthetic tumor networks for screening drug delivery systems.
AB  - Tumor drug delivery is a complex phenomenon affected by several elements in
      addition to drug or delivery vehicle's physico-chemical properties. A key factor
      is tumor microvasculature with complex effects including convective transport,
      high interstitial pressure and enhanced vascular permeability due to the presence
      of "leaky vessels". Current in vitro models of the tumor microenvironment for
      evaluating drug delivery are oversimplified and, as a result, show poor
      correlation with in vivo performance. In this study, we report on the development
      of a novel microfluidic platform that models the tumor microenvironment more
      accurately, with physiologically and morphologically realistic microvasculature
      including endothelial cell lined leaky capillary vessels along with 3D solid
      tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co
      cultured in the networks. Drug vehicle screening was demonstrated using GFP gene
      delivery by different formulations of nanopolymers. The synthetic tumor network
      was successful in predicting in vivo delivery efficiencies of the drug vehicles.
      The developed assay will have critical applications both in basic research, where
      it can be used to develop next generation delivery vehicles, and in drug
      discovery where it can be used to study drug transport and delivery efficacy in
      realistic tumor microenvironment, thereby enabling drug compound and/or delivery
      vehicle screening. 

PMID- 25599859
TI  - Mapping resistance to the Ug99 race group of the stem rust pathogen in a spring
      wheat landrace.
AB  - KEY MESSAGE: A new gene for Ug99 resistance from wheat landrace PI 374670 was
      detected on the long arm of chromosome 7A. Wheat landrace PI 374670 has seedling
      and field resistance to stem rust caused by Puccinia graminis f. sp tritici
      Eriks. & E. Henn (Pgt) race TTKSK. To elucidate the inheritance of resistance,
      216 BC1F2 families, 192 double haploid (DH) lines, and 185 recombinant inbred
      lines (RILs) were developed by crossing PI 374670 and the susceptible line LMPG
      6. The parents and progeny were evaluated for seedling resistance to Pgt races
      TTKSK, MCCFC, and TPMKC. The DH lines were tested in field stem rust nurseries in
      Kenya and Ethiopia. The DH lines were genotyped with the 90K wheat iSelect SNP
      genotyping platform. Goodness-of-fit tests indicated that a single dominant gene
      in PI 374670 conditioned seedling resistance to the three Pgt races. The seedling
      resistance locus mapped to the long arm of chromosome 7A and this result was
      verified in the RIL population screened with the flanking SNP markers using KASP
      assays. In the same region, a major QTL for field resistance was detected in a
      7.7 cM interval and explained 34-54 and 29-36% of the variation in Kenya and
      Ethiopia, respectively. Results from tests with specific Pgt races and the csIH81
      marker showed that the resistance was not due to Sr22. Thus, a new stem rust
      resistance gene or allele, either closely linked or allelic to Sr15, is
      responsible for the seedling and field resistance of PI 374670 to Ug99.

PMID- 25599858
TI  - Myocardial 14-3-3eta protein protects against mitochondria mediated apoptosis.
AB  - There is a definite cardioprotective role for 14-3-3eta protein against pressure
      overload induced cardiac hypertrophy and streptozotocin induced cardiac
      dysfunction in type 1 diabetes mellitus (DM). But it is not conclusive whether it
      has any influence on mitochondrial mediated cardiomyocyte apoptosis in type 2 DM.
      In order to test this hypothesis, we have used C57BL6/J (WT) mice with cardiac
      specific dominant negative mutation of 14-3-3eta protein (DN 14-3-3eta). Both WT
      and DN 14-3-3eta mice were fed with high fat diet (HFD) for 12weeks. Their body
      weight and blood glucose levels were measured weekly and compared with standard
      diet (SD) fed mice. By the end of 12weeks, echocardiography was performed. Frozen
      myocardial sections were prepared to stain the apoptotic cardiomyocytes using
      TUNEL staining. DN 14-3-3eta mice fed with HFD showed cardiac dysfunction as
      identified by the decreased fractional shortening and ejection fraction and
      increased cardiomyocyte apoptosis in TUNEL staining. Western blotting analysis
      using mitochondrial fraction of the ventricular tissue homogenates showed a
      significant reduction in the level of cytochrome c suggesting its translocation
      into cytoplasm, which may be crucial in inducing cardiomyocyte apoptosis. In
      addition, DN 14-3-3eta mice depicted significantly increased levels of NADPH
      oxidase subunits suggesting oxidative stress, a significant reduction in phospho
      apoptosis signal-regulating kinase-1 (p-Ask-1) and increase in Ask-1 and phospho
      c-Jun N-terminal kinase (p-JNK) levels suggesting activation of Ask-1/JNK
      signaling. These results suggest that 14-3-3eta has a protective role against
      mitochondria mediated cardiomyocyte apoptosis with the involvement of Ask-1/JNK
      signaling during HFD induced type 2 DM.

PMID- 25599860
TI  - The association of Varicella zoster virus reactivation with Bell's palsy in
      children.
AB  - OBJECTIVES: Bell's palsy is considered the most common cause of facial nerve
      paralysis in children. Although different theories have been postulated for its
      diagnosis, reactivation of the Varicella zoster virus (VZV) has been implicated
      as one of the causes of Bell's palsy. The aim of the study was to evaluate the
      association of Varicella-zoster virus infection with Bell's palsy and its outcome
      in children. METHODS: A total of 30 children with Bell's palsy were recruited and
      were assayed for evidence of VZV infection. The severity of facial nerve
      dysfunction and the recovery rate were evaluated according to House-Brackmann
      Facial Nerve Grading Scale (HB FGS). Paired whole blood samples from all patients
      were obtained at their initial visit and 3 weeks later, and serum samples were
      analyzed for VZV IgG and IgM antibodies using ELISA. RESULTS: A significantly
      higher percentage of Bell's palsy patients were seropositive for VZV IgM
      antibodies than controls (36.6% of patients vs 10% of controls) while for VZV IgG
      antibodies the difference was statistically nonsignificant. HB FGS in Bell's
      palsy patients with serologic evidence of VZV recent infection or reactivation
      showed a statistiacally significant less cure rate than other patients.
      CONCLUSIONS: VZV reactivation may be an important cause of acute peripheral
      facial paralysis in children. The appropriate diagnosis of VZV reactivation
      should be done to improve the outcome and the cure rate by the early use of
      antiviral treatment.

PMID- 25599861
TI  - Evaluation of pediatric voice handicap index and pediatric voice related quality
      of life before and after adenotonsillectomy in pediatric population.
AB  - OBJECTIVE: To study changes in Pediatric Voice Handicap Index (PVHI) and
      Pediatric Voice Related Quality of Life (PVRQOL) before and after
      adenotonsillectomy in short term follow up. METHODS: Quasi-experimental (before
      and after study). Eighty-six children aged 3-13 years (58 boys, 28 girls) with
      adenotonsillar problems (whether with obstructive or infectious surgical
      indications) who were admitted for adenotonsillectomy procedure. Parents of
      children were asked to complete PVHI and PVRQOL questionnaires prior to surgery
      and 1 month after it. RESULTS: Reliability of the PVRQOL and PVHI was established
      by evaluation of Cronbach alpha value. Cronbach alpha for PVHI was 0.92 and for
      PVRQOL it was 0.83. Preoperative values for the PVHI were: mean+/-SD; 14.39+/
      14.65. Preoperative values for the PVRQOL were: mean+/-SD; 92.60+/-10.82. PVHI
      showed significant improvement after surgery: mean+/-SD; 2.93+/-6.98 (P<0.001).
      Postoperative PVRQOL had a significant improvement: mean+/-SD; 98.11+/-5.82
      (P<0.001). CONCLUSION: Adenotonsillectomy improved PVHI and PVRQOL scores in
      children with adenotonsillar problems, regardless of obstructive or infectious
      surgical indications.

PMID- 25599863
TI  - Two-Stage Progressive Femoral Lowering Followed by Cementless Total Hip
      Arthroplasty for Treating Crowe IV-Hartofilakidis Type 3 Developmental Dysplasia
      of the Hip.
AB  - High developmental dysplasia of the hip is commonly treated with total hip
      arthroplasty and shortening osteotomy. We present a two stage technique,
      consisting of progressive femoral lowering followed by total hip arthroplasty.
      The clinico-radiographic results of eleven patients (twelve hips) who were
      operated on with the two-stage technique were evaluated at a mean follow-up of 11
      +/- 5 years. At the final follow-up, ten patients (eleven hips) had a mean Harris
      hip score of 85 +/- 5 points with no implant loosening. One patient (one hip) was
      revised at 5 years due to infection. No neurovascular complications were observed
      in any patients. With this technique, we could place the cup in the anatomical
      position and obtain complete limb symmetry with excellent clinical results at
      long-term.

PMID- 25599862
TI  - Establishment and characterization of DB-1: a leptin receptor-deficient murine
      macrophage cell line.
AB  - Metabolic and immune mediators activate many of the same signal transduction
      pathways. Therefore, molecules that regulate metabolism often affect immune
      responses. Leptin is an adipokine that exemplifies this interplay. Leptin is the
      body's major nutritional status sensor, but it also plays a key role in immune
      system regulation. To provide an in vitro tool to investigate the link between
      leptin and innate immunity, we immortalized and characterized a leptin receptor
      deficient macrophage cell line, DB-1. The cell line was created using bone marrow
      cells from leptin receptor-deficient mice. Bone marrow cells were differentiated
      into macrophages by culturing them with recombinant mouse macrophage colony
      stimulating factor, and passaged when confluent for 6 months. The cells
      spontaneously immortalized at approximately passage 20. Cells were cloned twice
      by limiting dilution cloning prior to characterization. The macrophage cell line
      is diploid and grows at a linear rate for 4-5 days before reaching the growth
      plateau. The cells are MAC-2 and F4/80 positive and have phagocytic activity
      similar to primary macrophages from wild-type and leptin receptor-deficient mice.
      DB-1 cells were responsive to stimulation with interferon-gamma as measured by
      increase in Nos2 transcript levels. In addition, DB-1 macrophages are not
      responsive to the chemotactic signaling of adipocyte conditioned media nor leptin
      when compared to primary WT macrophages. We believe that DB-1 cells provide a
      dependable tool to study the role of leptin or the leptin receptor in obesity
      associated inflammation and immune system dysregulation. 

PMID- 25599864
TI  - Anterior hip dislocation in children with neurological disorders. A retrospective
      study of ten operated hips.
AB  - INTRODUCTION: Patients with neurological disorders often exhibit dislocation or
      subluxation of the hip. Anterior dislocation is rare, little known, and often
      associated with deformities. Its surgical treatment has rarely been studied.
      HYPOTHESIS: Hip surgery (with open reduction, femoral and pelvic osteotomy, and
      adapted tenotomies) could provide a centered hip that is supple and painless.
      MATERIALS AND METHODS: Ten hips (seven dislocated, three subluxated) in six
      patients with a mean age of 8.3 years were operated between 1995 and 2009 and
      revised with a mean follow-up of 6.5 years. The deformities comprised four cases
      of abduction, extension, and external rotation and six cases of adduction,
      extension, and external rotation. Four patients had lost the ability to walk or
      maintain the sitting position. Intraoperative findings were an increased neck
      shaft angle, anterosuperior acetabular dysplasia, and in only one case increased
      femoral anteversion. In all cases of dislocation, open reduction was necessary,
      and all hips underwent pelvic and femoral osteotomy. RESULTS: At the longest
      follow-up, hips were centered on X-rays. Five patients could walk or sit as they
      had done before and hips were supple, with no deformities. DISCUSSION: The study
      of deformities and intraoperative findings is mandatory for surgical management,
      whose mid-term results are encouraging. Femoral anteversion does not seem to be
      excessive, but the increase of femoral valgus is constant, as is anterosuperior
      acetabular dysplasia. We propose a decision tree for the management of these
      patients. DESIGN OF STUDY: Retrospective. LEVEL OF SCIENTIFIC EVIDENCE: IV.

PMID- 25599865
TI  - Strategy and optimization of diagnostic imaging in painful hip in adults.
AB  - Diagnostic imaging strategy in painful hip depends on many factors, but in all
      cases, plain X-ray is the first investigation. It may be sufficient to reach
      diagnosis and determine treatment options. More effective but more expensive
      exploration is indicated in two circumstances: when plain X-ray is non
      contributive, and when diagnosis has been established but more accurate imaging
      assessment is needed to guide treatment. Following radiography, the choice of
      imaging techniques depends not only on the suspected pathology but also on the
      availability of equipment and its performance. MRI is probably the technique that
      provides the most comprehensive results; recent improved accessibility has
      significantly simplified the diagnostic algorithm. CT remains invaluable, and
      current techniques have reduced patient irradiation to a level similar to that of
      standard X-ray. Finally, cost is an important consideration in choosing the means
      of exploration, but the overall financial impact of the various strategies for
      diagnosis of painful hip is not well established. This article aims to provide a
      simple and effective diagnostic strategy for the assessment of painful hip,
      taking account of the clinical situation, and to detail the most typical
      semiologic patterns of each disease affecting this joint. 

PMID- 25599866
TI  - The relationship between fermented food intake and mortality risk in the European
      Prospective Investigation into Cancer and Nutrition-Netherlands cohort.
AB  - The objective of the present study was to investigate the relationship between
      total and subtypes of bacterial fermented food intake (dairy products, cheese,
      vegetables and meat) and mortality due to all causes, total cancer and CVD. From
      the European Prospective Investigation into Cancer and Nutrition-Netherlands
      cohort, 34 409 Dutch men and women, aged 20-70 years who were free from CVD or
      cancer at baseline, were included. Baseline intakes of total and subtypes of
      fermented foods were measured with a validated FFQ. Data on the incidence and
      causes of death were obtained from the national mortality register. Cox
      proportional hazards models were used to analyse mortality in relation to the
      quartiles of fermented food intake. After a mean follow-up of 15 (sd 2.5) years,
      2436 deaths occurred (1216 from cancer and 727 from CVD). After adjustment for
      age, sex, total energy intake, physical activity, education level, hypertension,
      smoking habit, BMI, and intakes of fruit, vegetables and alcohol, total fermented
      food intake was not found to be associated with mortality due to all causes
      (hazard ratio upper v. lowest quartile (HR(Q4 v. Q1)) 1.00, 95% CI 0.88, 1.13),
      cancer (HR(Q4 v. Q1) 1.02, 95% CI 0.86, 1.21) or CVD (HR(Q4 v. Q1) 1.04, 95 % CI
      0.83, 1.30). Bacterial fermented foods mainly consisted of fermented dairy foods
      (78 %) and cheese (16%). None of the subtypes of fermented foods was consistently
      related to mortality, except for cheese which was moderately inversely associated
      with CVD mortality, and particularly stroke mortality (HR(Q4 v. Q1) 0.59, 95% CI
      0.38, 0.92, P trend= 0.046). In conclusion, the present study provides no strong
      evidence that intake of fermented foods, particularly fermented dairy foods, is
      associated with mortality.

PMID- 25599867
TI  - Role of somatostatin and somatostatin receptor type 2 in postincisional
      nociception in rats.
AB  - Somatostatin (SST) and the somatostatin receptor type 2 (sstr2) are expressed in
      the superficial part (Laminae I-III) of the dorsal horn of the spinal cord. Since
      the neurons in these laminae also receive nociceptive sensation from the
      periphery, it was hypothesized that both SST and sstr2 could be involved in the
      modulation of nociceptive transmission. To the best of knowledge, there are no
      studies on the involvement of SST and sstr2 in hind paw incision model in rats,
      which mimics postoperative pain in humans. Sprague-Dawley rats were subjected to
      hind paw incision under isoflurane anaesthesia and the resulting mechanical
      allodynia and thermal hyperalgesia were evaluated for 5 days. In another set of
      animals, the spinal cord was isolated at specified time intervals after incision
      and examined for SST and sstr2 expression using immunohistochemistry and
      immunoblotting procedures. Finally, nociceptive parameters were again evaluated
      in incised rats, which had received SST (400 ug/kg i.p. three times per day).
      Blood glucose level and locomotor activity were determined after SST treatment.
      Both allodynia and hyperalgesia were highest immediately after incision. Spinal
      SST expression increased at 2 h. A further increase was noted on day 3.
      Expression of sstr2 increased initially but decreased at day 1. These changes
      could be due to exocytosis of SST and internalization of the ligand-receptor
      complex. SST injection significantly attenuated mechanical allodynia but not
      thermal hyperalgesia. Significant change in blood glucose level or locomotor
      activity was absent. SST appears to contribute to postincisional pain. This
      finding could be of clinical relevance.

PMID- 25599869
TI  - Comment on "A new method of microskin autografting with a Vaseline-based moisture
      dressing on granulation tissue".

PMID- 25599868
TI  - [Variability in the management of aneurysmal subarachnoid haemorrhage in Spain:
      Analysis of the prospective multicenter database from the Working Group on
      Neurovascular Diseases of the Spanish Society of Neurosurgery].
AB  - INTRODUCTION: In aneurysmal subarachnoid haemorrhage, endovascular or surgical
      exclusion of the aneurysm responsible for the bleeding is mandatory to prevent re
      bleeding. In Spain there is no data regarding the frequency of usage of the two
      techniques, the moment treatment is performed, the existence of variability among
      the different centres treating these patients or the factors that determine the
      election of the therapeutic modality. OBJECTIVES: 1) To describe the variability
      in the use of endovascular treatment or surgery in the treatment of these
      patients among the participating centres. 2) To establish which factors are
      related to the election of treatment and outcome. MATERIALS AND METHODS: Of all
      the patients included in the database, we selected 2,150 cases suffering
      confirmed aneurysmal subarachnoid haemorrhage from 10 centres that included
      patients regularly during the period between 2004 and 2012 with a data
      completeness index over 95%. A descriptive analysis on mode of aneurysm treatment
      was performed. A multivariate analysis of the factors related to treatment
      modality of the aneurysm and outcome was performed using logistic regression.
      RESULTS: The ratio endovascular/surgical treatment was 1.32. There was high
      variability among centres regarding the frequency of endovascular treatment (32
      80%). No treatment was given to 17% of the aneurysms, with this percentage being
      higher in the centres with lower rates of endovascular treatment. Lower volume
      centres treated aneurysms later. Age and poor clinical grade were factors related
      to the election of endovascular treatment, while middle cerebral artery location
      and unfavourable morphological criteria were factors of surgical treatment. The
      choice of treatment, guideline adherence and centre patient volume were not
      related to outcome. CONCLUSIONS: There is high variability in the election of
      treatment modality among centres in Spain. Endovascular treatment allows more
      patients to have their aneurysm treated. Guideline adherence is moderate.

PMID- 25599871
TI  - Ethics and meningiomas: From prudence to obstinacy? The position of the
      neurosurgeon (for treatment or insurance purposes) in the case of complaints
      concerning post-operative clinical deterioration.
AB  - To treat or not to treat an asymptomatic or pauci-symptomatic benign meningioma,
      that is the question. And if treatment is necessary, what is the best technique:
      radical resection, sub-total resection or radiotherapy? This question is also
      pertinent for meningiomas of the skull base, posterior part of the sagittal
      sinus, anterior part of the foramen magnum and cerebellopontine angle. When the
      results of the treatment are good, the patient and the surgeon are satisfied. But
      when a new neurological deficit appears after the treatment, the patient is
      entitled to obtain compensation. What should be the position of the specialist
      medical assessor in this situation when the prognosis of these benign tumors is
      unknown? Is the preoperative information that is due to the patient complete,
      objective and sufficient? Is the therapeutic indication unquestionable? Is the
      technique irreproachable? For meningiomas, there is no "evidence-based medicine";
      the therapeutic option is often based on the personal experience and/or the
      education of the surgeon and thus is, in fact, highly subjective.

PMID- 25599870
TI  - Phenotypic and functional modulation of 20-30 year old dermal fibroblasts by mid-
      and late-gestational keratinocytes in vitro.
AB  - Fetal wound healing occurs rapidly and without scar formation early in gestation,
      but the mechanisms underlying this scarless healing are poorly understood. This
      study explores the phenotypic and functional modulation of 20-30 year old dermal
      fibroblasts by mid- and late-gestational keratinocytes (KCs) in vitro. Human KCs
      of different gestational ages were isolated, characterized, and co-cultured with
      human 20-30 year old fibroblasts. Gene expression and protein levels of TGF-beta
      family members, precollagen, collagen, matrix metalloproteinases (MMPs), and the
      tissue inhibitors of metalloproteinases (TIMPs) were measured in the fibroblasts.
      Mid-gestational KCs promoted faster proliferation and migration of fibroblasts
      than late-gestational KCs. Additionally, significant differences in gene
      expression and protein levels of some markers were observed in fibroblasts co
      cultured with mid- or late-gestational KCs. Fibroblasts co-cultured with mid
      gestational KCs for 48 h exhibited downregulated gene expression of precollagen
      1, collagen 1, TGF-beta1, TGF-beta2, TIMP-2 and TIMP-3, while precollagen 3,
      collagen 3, TGF-beta3, and MMP-1, -2, -3, -9 and -14 were upregulated. In
      contrast, late-gestational KCs exhibited downregulated TIMP-1, TIMP-2 and TIMP-3
      levels, while collagen 1, TGF-beta2, TGF-beta3, and MMP-2, -3, -9 and -14 were
      upregulated. Moreover, statistically significant differences in expression levels
      of precollagen 1, precollagen 3, collagen 1, TGF-beta1, -beta2, and -beta3, MMP
      1, -3 and MMP-14, TIMP-1 and TIMP-2 were found between fibroblasts co-cultured
      with mid- and late-gestational KCs. Furthermore, cytokine levels of IL-1a and HB
      EGF were found to be statistically different between conditioned medium from mid-
      and late-gestational KCs. Therefore, the gestational age of KCs appears to have
      an important effect on scarless wound healing in the human fetus.

PMID- 25599872
TI  - Monte Carlo simulation of the response functions of CdTe detectors to be applied
      in x-ray spectroscopy.
AB  - In this work, the energy response functions of a CdTe detector were obtained by
      Monte Carlo (MC) simulation in the energy range from 5 to 160keV, using the
      PENELOPE code. In the response calculations the carrier transport features and
      the detector resolution were included. The computed energy response function was
      validated through comparison with experimental results obtained with (241)Am and
      (152)Eu sources. In order to investigate the influence of the correction by the
      detector response at diagnostic energy range, x-ray spectra were measured using a
      CdTe detector (model XR-100T, Amptek), and then corrected by the energy response
      of the detector using the stripping procedure. Results showed that the CdTe
      exhibits good energy response at low energies (below 40keV), showing only small
      distortions on the measured spectra. For energies below about 80keV, the
      contribution of the escape of Cd- and Te-K x-rays produce significant distortions
      on the measured x-ray spectra. For higher energies, the most important correction
      is the detector efficiency and the carrier trapping effects. The results showed
      that, after correction by the energy response, the measured spectra are in good
      agreement with those provided by a theoretical model of the literature. Finally,
      our results showed that the detailed knowledge of the response function and a
      proper correction procedure are fundamental for achieving more accurate spectra
      from which quality parameters (i.e., half-value layer and homogeneity
      coefficient) can be determined. 

PMID- 25599873
TI  - The effect of milrinone on right and left ventricular function when used as a
      rescue therapy for term infants with pulmonary hypertension.
AB  - INTRODUCTION: Milrinone may be an appropriate adjuvant therapy for infants with
      persistent pulmonary hypertension of the newborn. We aimed to describe the effect
      of milrinone administration on right and left ventricular function in infants
      with persistent pulmonary hypertension not responding to inhaled nitric oxide
      after 4 hours of administration. MATERIALS AND METHODS: This is a retrospective
      review of infants born after or at 34 weeks of gestation with persistent
      pulmonary hypertension who received milrinone treatment. The primary endpoint was
      the effect of milrinone on myocardial performance and haemodynamics, including
      right and left ventricular outputs, tissue Doppler velocities, right ventricle
      and septal strain, and strain rate. Secondary endpoints examined included
      duration of inhaled nitric oxide and oxygen support. RESULTS: A total of 17
      infants with a mean (standard deviation) gestation and birth weight of 39.8 (2.0)
      weeks and 3.45 (0.39) kilograms, respectively, were included in the study. The
      first echocardiogram was performed 15 hours after the commencement of nitric
      oxide inhalation. Milrinone treatment was started at a median time of 1 hour
      after the echocardiogram and was associated with an increase in left ventricular
      output (p=0.04), right ventricular output (p=0.004), right ventricle strain
      (p=0.01) and strain rate (p=0.002), and left ventricle s' (p<0.001) and a'
      (p=0.02) waves. There was a reduction in nitric oxide dose and oxygen requirement
      over the subsequent 72 hours (all p<0.05). CONCLUSION: The use of milrinone as an
      adjunct to nitric oxide is worth further exploration, with preliminary evidence
      suggesting an improvement in both oxygenation and myocardial performance in this
      group of infants.

PMID- 25599875
TI  - Alzheimer's Abeta interacts with cellular prion protein inducing neuronal
      membrane damage and synaptotoxicity.
AB  - A major feature of Alzheimer's disease is the accumulation of beta-amyloid
      (Abeta) peptide in the brain. Recent studies have indicated that Abeta oligomers
      (Abetao) can interact with the cellular prion protein (PrPc). Therefore, this
      interaction might be driving some of Abeta toxic effects in the synaptic region.
      In the present study, we report that Abetao binds to PrPc in the neuronal
      membrane playing a role on toxic effects induced by Abeta. Phospholipase C
      enzymatic cleavage of PrPc from the plasma membrane attenuated the association of
      Abetao to the neurons. Furthermore, an anti-PrP antibody (6D11) decreased the
      association of Abetao to hippocampal neurons with a concomitant reduction in
      Abetao and PrPc co-localization. Interestingly, this antibody blocked the
      increase in membrane conductance and intracellular calcium induced by Abetao.
      Thus, the data indicate that PrPc plays a role on the membrane perforations
      produced by Abetao, the increase in calcium ions and the release of synaptic
      vesicles that subsequently leads to synaptic failure. Future studies blocking
      Abetao interaction with PrPc could be important for the discovery of new
      therapeutic strategies for Alzheimer's disease. 

PMID- 25599874
TI  - Longitudinal follow-up and characterization of a robust rat model for Parkinson's
      disease based on overexpression of alpha-synuclein with adeno-associated viral
      vectors.
AB  - Testing of new therapeutic strategies for Parkinson's disease (PD) is currently
      hampered by the lack of relevant and reproducible animal models. Here, we
      developed a robust rat model for PD by injection of adeno-associated viral
      vectors (rAAV2/7) encoding alpha-synuclein into the substantia nigra, resulting
      in reproducible nigrostriatal pathology and behavioral deficits in a 4-week time
      period. Progressive dopaminergic dysfunction was corroborated by histopathologic
      and biochemical analysis, motor behavior testing and in vivo microdialysis. L
      DOPA treatment was found to reverse the behavioral phenotype. Non-invasive
      positron emission tomography imaging and magnetic resonance spectroscopy allowed
      longitudinal monitoring of neurodegeneration. In addition, insoluble alpha
      synuclein aggregates were formed in this model. This alpha-synuclein rat model
      shows improved face and predictive validity, and therefore offers the possibility
      to reliably test novel therapeutics. Furthermore, it will be of great value for
      further research into the molecular pathogenesis of PD and the importance of
      alpha-synuclein aggregation in the disease process.

PMID- 25599876
TI  - Labrum and rotator cuff injuries in the throwing athlete.
AB  - The large amount of force imparted across the shoulder during the act of throwing
      makes the glenohumeral joint highly susceptible to injury in the athlete
      performing overhead throwing motions. The bony incongruity of the shoulder
      enables greater range of motion than any other joint in the body, but it also
      results in significant strain on the surrounding soft tissues during the throwing
      motion. Throwers can present with acute injuries, but more commonly they suffer
      from chronic overuse conditions resulting from repetitive overload. Proper
      management requires early recognition with treatment directed toward the
      athlete's safe return to sports. Failure to institute an appropriate management
      strategy may result in significant complications, including prolonged disability,
      progression of symptoms, and further injury. We discuss the functional anatomy,
      pathophysiology, clinical presentation, evaluation, and treatment of common
      injuries of the glenoid labrum and rotator cuff in the overhead throwing athlete.

PMID- 25599877
TI  - Unexpected spatiotemporal abundance of infected Culex restuans suggest a greater
      role as a West Nile virus vector for this native species.
AB  - Difficulties in correctly differentiating Culex restuans mosquitoes from Culex
      pipiens have left the spatiotemporal mechanisms underlying the epidemiology of
      West Nile virus (WNV) in the northeastern United States largely unresolved. We
      performed weekly surveys across a natural to urban gradient of sites in central
      New Jersey (USA) and used a rapid and cheap DNA extraction and a species-specific
      PCR assay to create single species pools for WNV testing. To assess seasonal
      trends we combined these results with WNV surveillance records generated from
      grouped Cx. restuans/Cx. pipiens pools tested in 2011-2012. Cx.restuans was found
      to be highly abundant within all sites and reached especially high abundance in
      urban wetland habitats greatly disturbed by human action. In contrast, the
      seasonal presence of Cx. pipiens was greatest in residential and urban habitats
      and its presence in natural areas was minimal throughout the season. WNV
      infection rates in both species were similar but Cx. restuans was consistently
      found infected first and more frequently, even as early as May, whereas WNV was
      first detected in Cx. pipiens in late July. WNV activity peaked during the month
      of August when WNV was commonly isolated from both species. The peak in WNV
      activity in August observed for both species was consistent with data from 2011
      to 2012 when Cx. restuans and Cx. pipiens were grouped, although analyzing single
      species pools increased overall predicted infection levels. Our results support
      the preeminence of Cx. restuans as an enzootic vector of WNV and strongly suggest
      this species has become a "native invasive" exploiting human modified habitats
      and reaching very high abundance there. Importantly, high infection rates in
      disturbed wetland sites with high populations of Cx. restuans suggest this
      species may enable the introduction of WNV to urbanized environments where both
      Culex contribute to transmission potentiating disease risk. 

PMID- 25599878
TI  - An increasing prevalence of recombinant GII norovirus in pediatric patients with
      diarrhea during 2010-2013 in China.
AB  - Noroviruses are the primary cause of acute nonbacterial gastroenteritis in humans
      and are responsible for nearly half of gastroenteritis cases globally. The
      norovirus strain variants have been circulating in underdeveloped regions in
      western China, where pediatric diarrhea acts as the major public health concern.
      The study aims to identify the epidemic genotypes of norovirus and explore their
      genetic characteristics in Chongqing, China. By performing a hospital-based
      surveillance from 2010 to 2013, we identified a significant shift of the
      predominant Norovirus strains in recent 4years in the studied area. The
      GII.4_Sydney_2012 and GII.12/GII.3 strains replaced GII.4_2006b and
      GII.4_NewOrleans_2009 to become the predominant genotypes, with the proportion of
      ORF1/ORF2 recombinants rising steadily from 2010 to 2013. A new GII.12/GII.3
      variant that was seldom detected became a predominant genotype during the study
      course. Several distinct genotypes of norovirus, including GII.16/GII.2,
      GII.21/GII.3, GII.15 and GII.6, were also detected. The rising circulation of
      recombination in Chongqing illustrated the significance of recombination,
      especially in the ORF1/ORF2 overlap region, in the evolution and epidemic of
      norovirus. The epidemic of GII.12/GII.3 in Chongqing also serves as a reminder
      that prolonged surveillance is warranted for better prevention and control of
      norovirus infection. 

PMID- 25599880
TI  - Comorbidity of diabetes and obstructive sleep apnea in hospitalized patients.
AB  - Obstructive sleep apnea (OSA) and type 2 diabetes are two morbidities commonly
      encountered in the hospitalized setting. Both diseases will present with an array
      of complications if not managed in a timely, competent manner. However, a growing
      body of evidence suggests a link between these two pathologies. It is our hope
      that through careful review of the literature, we may generate heightened
      awareness of the OSA/diabetes comorbidity. Through better understanding of these
      conditions and their interactions, we may insure efficient management in the
      clinical setting and prevent exacerbation of common complications. 

PMID- 25599879
TI  - An optimized protocol for isolating lymphoid stromal cells from the intestinal
      lamina propria.
AB  - Mesenchymal stromal cells in lymphoid organs, also called lymphoid stromal cells
      (LSCs), play a pivotal role in immunity by forming specialized microenvironments
      that provide signals for leukocyte migration, positioning, and survival. Best
      characterized in lymphoid organs, LSCs are also abundant in the intestinal
      mucosa, which harbors a rich repertoire of immune cells. However, the lack of
      efficient procedures for isolation and purification of LSCs from the intestine
      has been a major limitation to their characterization. Here we report a new
      method to efficiently isolate, in addition to immune cells, viable lymphoid
      stromal cells and other stromal subsets from the intestinal lamina propria for
      subsequent phenotypic and functional analysis. 

PMID- 25599883
TI  - Thermal vibration of a single-walled carbon nanotube predicted by semiquantum
      molecular dynamics.
AB  - Quantum effects should be considered in the thermal vibrations of carbon
      nanotubes (CNTs). To this end, molecular dynamics based on modified Langevin
      dynamics, which accounts for quantum statistics by introducing a quantum heat
      bath, is used to simulate the thermal vibration of a cantilevered single-walled
      CNT (SWCNT). A nonlocal elastic Timoshenko beam model with quantum effects
      (TBQN), which can take the effect of microstructure into consideration, has been
      established to explain the resulting power spectral density of the SWCNT. The
      root of mean squared (RMS) amplitude of the thermal vibration of the SWCNT
      obtained from semiquantum molecular dynamics (SQMD) is lower than that obtained
      from classical molecular dynamics, especially at very low temperature and high
      order modes. The natural frequencies of the SWCNT obtained from the Timoshenko
      beam model are closer to those obtained from molecular dynamics if the nonlocal
      effect is taken into consideration. However, the nonlocal Timoshenko beam model
      with the law of energy equipartition (TBCN) can only predict the RMS amplitude of
      the SWCNT obtained from classical molecular dynamics without considering quantum
      effects. The RMS amplitude of the SWCNT obtained from SQMD and that obtained from
      TBQN coincide very well. These results indicate that quantum effects are
      important for the thermal vibration of the SWCNT in the case of high-order modes,
      short length and low temperature. 

PMID- 25599882
TI  - Low-cost modular phonosurgery training station: development and validation.
AB  - OBJECTIVE: Phonosurgery requires technical precision and careful tissue handling.
      Typically, phonosurgical procedures require single-operator techniques, making it
      difficult for novice residents to develop necessary skills. We developed a low
      cost phonosurgery simulator to allow practice and acquisition of microlaryngeal
      skills. STUDY DESIGN: Validation study assessing the simulator's face and content
      validity in surgical education. METHODS: For construction, the simulator is
      composed of a simulation station and laryngeal modules, each constructed with
      inexpensive, easily accessible materials including plywood and polyvinyl chloride
      pipe. Laryngeal modules were constructed using rubber bands, bacitracin, and
      plastic wrap to simulate layers of the true vocal fold. Three separate modules
      were developed to address specific skills: 1) basic instrumentation; 2) papilloma
      debulking; 3) subepithelial and epithelial lesion excision. Papillomas,
      subepithelial, and epithelial lesions were simulated with grapefruit, caulk, and
      suture, respectively. The Kantor-Berci video laryngoscope was used for
      visualization. For validation, face and content validity were assessed by
      attending otolaryngologists (n = 16), who performed the three specific skills
      using the simulation station and completed a 5-point Likert-type postsimulation
      questionnaire. RESULTS: Most participants (89%) strongly agreed that the
      simulator incorporates essential phonosurgery skills and that portions of the
      model simulated an actual case (content validity). All participants (100%) agreed
      that the simulator is an adequate training device to increase resident competency
      and would be interested in using it to train residents (face validity).
      CONCLUSION: This simulator has the potential to be an important component of
      phonosurgical education and preoperative preparation. Advantages include a
      realistic experience, modular design, and inexpensive construction. LEVEL OF
      EVIDENCE: N/A.

PMID- 25599884
TI  - Comparison of the boomerang wire vascular access management system versus manual
      compression alone during percutaneous diagnostic and interventional
      cardiovascular procedures: The boomerangTM wire vascular access management trial
      II.
AB  - OBJECTIVES: To evaluate the use of the BoomerangTM Wire as an adjunct to manual
      compression (MC) in patients requiring diagnostic (Dx) or interventional (Ix)
      percutaneous procedures. BACKGROUND: MC remains the standard of care for closure
      of femoral artery access sites. Adjunctive use of a device to facilitate closure,
      reduce time to hemostasis (TTH) and ambulation (TTA) without increasing
      complication rates could reduce costs and hospital resource demands. METHODS: The
      BoomerangTM Trial was a prospective, multicenter, randomized, controlled trial
      comparing use of the BoomerangTM wire, (Cardiva Medical, Sunnyvale, CA) in
      conjunction with MC versus MC alone to achieve hemostasis in Dx and Ix patients
      undergoing percutaneous procedures requiring femoral artery access. Endpoints
      included TTH, TTA, major, and minor access-site related complications. Subjects
      were randomized 3:1, Boomerang versus MC. RESULTS: No minor or major device
      related adverse events were reported. Nondevice related complication rates were 3
      (0.9%) in the Boomerang arm (n = 327) and 1 (0.8%) in MC arm (n = 123). Mean TTH
      for Boomerang vs. MC was 11.2 +/- 4.3 vs. 23.2 +/- 11 min for Dx (P < 0.0001) and
      13.9 +/- 5.4 vs. 38.4 +/- 57.3 min for Ix patients (P < 0.0001). Mean TTA for
      Boomerang vs. MC was 3.3 +/- 3.0 vs. 4.5 +/- 2.0 hr (P < 0.0001)for Dx and 5.4 +/
      3.3 vs. 6.8 +/- 3.2 hr (P < 0.0001) for Ix patients. CONCLUSIONS: BoomerangTM
      use, in conjunction with MC, was associated with low rates of complications and
      demonstrated that BoomerangTM as an adjunct to MC can significantly decrease TTH
      and TTA after both Dx and Ix procedures. (c) 2015 Wiley Periodicals, Inc.

PMID- 25599885
TI  - The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe
      soybean leaves in high-fat-diet mice.
AB  - The present study investigated the anti-obesity and anti-diabetic effects of
      kaempferol glycoside (KG) fractions which were composed of four kaempferol
      glycosides and purified from unripe Jindai-soybean (Edamame) leaves in C57BL/6J
      mice. High fat-fed mice treated with 0.15% dietary KG for 92 days had reduced
      body weight, adipose tissue and TG levels compared to the high fat-fed control
      group. KG-treatment also decreased fasting blood glucose, serum HbA1c (hemoglobin
      A(1c)) levels and improved insulin resistance. Gene expression analysis of the
      liver showed that KG decreased peroxisome proliferator-activated receptor (PPAR
      gamma) and sterol regulatory element-binding protein (SREBP-1c) expression. These
      results suggest that KG reduced the accumulation of adipose tissue, improving
      hyperlipidemia as well as diabetes in obese mice by increasing lipid metabolism
      through the downregulation of PPAR-gamma and SREBP-1c. Thus, KG may have an anti
      obesity and anti-diabetic potential.

PMID- 25599886
TI  - Reasons for and reservations about research participation in acutely injured
      adults.
AB  - PURPOSE: The purpose of this study was to explore the reasons adult patients
      seeking emergency department care for minor injuries agree to participate in
      clinical research and to identify their reservations about participating in a
      research study. DESIGN AND METHODS: This is a secondary analysis of data from a
      longitudinal cohort study of 275 adults who sought emergency department care for
      physical injury and were followed over 12 months. At the final interview,
      participants were asked open-ended short-answer questions about their perception
      of participating in the study. Free text responses were analyzed using
      conventional content analysis. FINDINGS: The final sample of 214 participants was
      composed equally of males and females, predominantly Black (54%) and White (42%),
      with a mean age of 41 years. Six themes about reasons for participation emerged
      from free text responses: being asked, altruism, potential for personal benefit,
      financial gain, curiosity, and valuing or knowledge of research. Most did not
      report reservations. Those reservations identified included time constraints,
      confidentiality, and whether patients felt well suited to fulfill the study
      requirements. CONCLUSIONS: Although injured patients are identified by the
      research community as vulnerable, they are willing to participate in research
      studies for diverse reasons, and their participation is commonly associated with
      positive experiences. CLINICAL RELEVANCE: Understanding perceptions of
      participants' experiences of being in a research study after acute injury can
      guide researchers to improve future study protocols and recruitment strategies in
      order to optimize participants' experiences. Recruitment and retention into
      clinical research studies is essential to build nursing science to enhance the
      recovery of injured individuals.

PMID- 25599887
TI  - Investigational therapies up to Phase II which target PDGF receptors: potential
      anti-cancer therapeutics.
AB  - INTRODUCTION: The platelet-derived growth factor receptor (PDGFR) pathway has
      important functions in cell growth and, by overexpression or mutation, could also
      be a driver for tumor development. Moreover, PDGFR is expressed in a tumoral
      microenvironment and could promote tumorigenesis. With these biological
      considerations, the PDGFR pathway could be an interesting target for
      therapeutics. Currently, there are many molecules under development that target
      the PDGFR pathway in different types of cancer. AREAS COVERED: In this review,
      the authors report the different molecules under development, as well as those
      approved albeit briefly, which inhibit the PDGFR pathway. Furthermore, the
      authors summarize their specificities, their toxicities, and their development.
      EXPERT OPINION: Currently, most PDGFR kinase inhibitors are multikinase
      inhibitors and therefore do not simply target the PDGFR pathway. The development
      of more specific PDGFR inhibitors could improve drug efficacy. Moreover,
      selecting tumors harboring mutations or amplifications of PDGFR could improve
      outcomes associated with the use of these molecules. The authors believe that new
      technologies, such as kinome arrays or pharmacologic assays, could be of benefit
      to understanding resistance mechanisms and develop more selective PDGFR
      inhibitors.

PMID- 25599888
TI  - Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the
      Asperger Subcategory.
AB  - Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but
      there is evidence of conversion or comorbid overlap. The objective of this paper
      was to explore whether deficits in sensory gating, as seen in some schizophrenia
      patients, can also be found in a group of ASD children compared to neurotypically
      developed children. An additional aim was to investigate the possibility of
      subdividing our ASD sample based on these gating deficits. In a case-control
      design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and
      39 healthy matched controls (8-12 years) and screened for differences between
      groups and within the ASD group. We did not find disturbances in auditory P50 and
      N100 filtering in the group of ASD children as a whole, nor did we find abnormal
      P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus
      was significantly reduced in the Asperger subgroup compared to healthy controls.
      In contrast to what is usually reported for patients with schizophrenia, we found
      no evidence for sensory gating deficits in our group of ASD children taken as a
      whole. However, reduced P50 amplitude to conditioning stimuli was found in the
      Asperger group, which is similar to what has been described in some studies in
      schizophrenia patients. There was a positive correlation between the P50
      amplitude of the conditioning stimuli and anxiety score in the pervasive
      developmental disorder not otherwise specified group, which indicates a relation
      between anxiety and sensory registration in this group.

PMID- 25599889
TI  - beta-Strand mimetic foldamers rigidified through dipolar repulsion.
AB  - Many therapeutically relevant protein-protein interactions contain hot-spot
      regions on secondary structural elements, which contribute disproportionately to
      binding enthalpy. Mimicry of such alpha-helical regions has met with considerable
      success, however the analogous approach for the beta-strand has received less
      attention. Presented herein is a foldamer for strand mimicry in which dipolar
      repulsion is a central determinant of conformation. Computation as well as
      solution- and solid-phase data are consistent with an ensemble weighted almost
      exclusively in favor of the desired conformation. 

PMID- 25599892
TI  - Variation in Utilization of Health Care Services for Rural VA Enrollees With
      Mental Health-Related Diagnoses.
AB  - PURPOSE: Rural-dwelling Department of Veterans Affairs (VA) enrollees are at high
      risk for a wide variety of mental health-related disorders. The objective of this
      study is to examine the variation in the types of mental and nonmental health
      services received by rural VA enrollees who have a mental health-related
      diagnosis. METHODS: The Andersen and Aday behavioral model of health services use
      and the Agency for Healthcare Research and Quality Medical Expenditure Panel
      Survey (MEPS) data were used to examine how VA enrollees with mental health
      related diagnoses accessed places of care from 1999 to 2009. Population survey
      weights were applied to the MEPS data, and logit regression was conducted to
      model how predisposing, enabling, and need factors influence rural veteran health
      services use (measured by visits to different places of care). Analyses were
      performed on the subpopulations: rural VA, rural non-VA, urban VA, and urban non
      VA enrollees. FINDINGS: For all types of care, both rural and urban VA enrollees
      received care from inpatient, outpatient, office-based, and emergency room
      settings at higher odds than urban non-VA enrollees. Rural VA enrollees also
      received all types of care from inpatient, office-based, and emergency room
      settings at higher odds than urban VA enrollees. Rural VA enrollees had higher
      odds of a mental health visit of any kind compared to urban VA and non-VA
      enrollees. CONCLUSIONS: Based on these variations, the VA may want to develop
      strategies to increase screening efforts in inpatient settings and emergency
      rooms to further capture rural VA enrollees who have undiagnosed mental health
      conditions.

PMID- 25599891
TI  - Accelerated five-dimensional echo planar J-resolved spectroscopic imaging:
      Implementation and pilot validation in human brain.
AB  - PURPOSE: To implement an accelerated five-dimensional (5D) echo-planar J-resolved
      spectroscopic imaging sequence combining 3 spatial and 2 spectral encoding
      dimensions and to apply the sequence in human brain. METHODS: An echo planar
      readout was used to acquire a single spatial and a single spectral dimension
      during one readout. Nonuniform sampling was applied to the two phase-encoded
      spatial directions and the indirect spectral dimension. Nonlinear reconstruction
      was used to minimize the l1-norm or the total variation and included a spectral
      mask to enhance sparsity. Retrospective reconstructions at multiple
      undersamplings were performed in phantom. Ten healthy volunteers were scanned
      with 8* undersampling and compared to a fully sampled single slice scan. RESULTS:
      Retrospective reconstruction of fully sampled phantom data showed excellent
      quality at 4*, 8*, 12*, and 16* undersampling using either reconstruction method.
      Reconstruction of prospectively acquired in vivo scans with 8* undersampling
      showed excellent quality in the occipito-parietal lobes and good quality in the
      frontal lobe, consistent with the fully sampled single slice scan. CONCLUSION: By
      utilizing nonuniform sampling with nonlinear reconstruction, 2D J-resolved
      spectra can be acquired over a 3D spatial volume with a total scan time of 20
      min, which is reasonable for in vivo studies.

PMID- 25599893
TI  - Effects of clay on fat necrosis and carcass characteristics in Japanese Black
      steers.
AB  - Twenty 10-month-old Japanese Black steers were used to evaluate the effects of
      clay on fat necrosis and carcass characteristics. Ten steers (Clay group) were
      fed the clay (50 g/day) during 10-30 months of age. The other 10 steers (Control
      group) were not fed it. There was no significant difference in body weight or
      average daily gain between the two groups (P > 0.05). The occurrence of fat
      necrotic mass in the Clay group (30%) was lower (P < 0.05) than that in the
      Control group (90%) at slaughter. The size of necrotic masses in the Clay group
      was smaller (P < 0.05) than that in the Control group. There was no significant
      difference in the marbling score, beef color, Longissimus muscle area or
      subcutaneous fat thickness between the two groups. These results suggest that the
      clay prevented the occurrence of fat necrosis and did not affect the carcass
      characteristics in Japanese Black steers.

PMID- 25599890
TI  - COIL: a methodology for evaluating malarial complexity of infection using
      likelihood from single nucleotide polymorphism data.
AB  - BACKGROUND: Complex malaria infections are defined as those containing more than
      one genetically distinct lineage of Plasmodium parasite. Complexity of infection
      (COI) is a useful parameter to estimate from patient blood samples because it is
      associated with clinical outcome, epidemiology and disease transmission rate.
      This manuscript describes a method for estimating COI using likelihood, called
      COIL, from a panel of bi-allelic genotyping assays. METHODS: COIL assumes that
      distinct parasite lineages in complex infections are unrelated and that genotyped
      loci do not exhibit significant linkage disequilibrium. Using the population
      minor allele frequency (MAF) of the genotyped loci, COIL uses the binomial
      distribution to estimate the likelihood of a COI level given the prevalence of
      observed monomorphic or polymorphic genotypes within each sample. RESULTS: COIL
      reliably estimates COI up to a level of three or five with at least 24 or 96
      unlinked genotyped loci, respectively, as determined by in silico simulation and
      empirical validation. Evaluation of COI levels greater than five in patient
      samples may require a very large collection of genotype data, making sequencing a
      more cost-effective approach for evaluating COI under conditions when disease
      transmission is extremely high. Performance of the method is positively
      correlated with the MAF of the genotyped loci. COI estimates from existing SNP
      genotype datasets create a more detailed portrait of disease than analyses based
      simply on the number of polymorphic genotypes observed within samples.
      CONCLUSIONS: The capacity to reliably estimate COI from a genome-wide panel of
      SNP genotypes provides a potentially more accurate alternative to methods relying
      on PCR amplification of a small number of loci for estimating COI. This approach
      will also increase the number of applications of SNP genotype data, providing
      additional motivation to employ SNP barcodes for studies of disease epidemiology
      or control measure efficacy. The COIL program is available for download from
      GitHub, and users may also upload their SNP genotype data to a web interface for
      simple and efficient determination of sample COI.

PMID- 25599896
TI  - A panel of biomarkers for disease severity in atopic dermatitis.

PMID- 25599894
TI  - Pediatric refractory epilepsy: A decision analysis comparing medical versus
      surgical treatment.
AB  - OBJECTIVES: To quantify the life expectancy of surgically eligible children with
      refractory epilepsy comparing two treatment strategies: medical treatment only
      versus epilepsy surgery. METHODS: Decision analysis model populated with
      available parameters from the literature. One- and two-way sensitivity analyses
      and second-order Monte Carlo simulations evaluated the robustness of the results
      across wide variations of the input parameters. The time horizon was lifetime and
      the main outcome was life expectancy. RESULTS: Across the range of pediatric
      ages, epilepsy surgery yielded a higher life expectancy. For a cohort of 10-year
      old children with refractory epilepsy, the gain in life expectancy with epilepsy
      surgery (compared to medical treatment only) was 5.9 years for temporal epilepsy
      and 5.6 years for extratemporal epilepsy. One- and two-way sensitivity analyses
      and second-order Monte Carlo simulations demonstrated the robustness of results
      across a wide variation of input parameters. There was no adjustment for quality
      of life, but we estimated the percentage of life expectancy spent in seizure
      freedom. For a cohort of 10-year-old patients with refractory epilepsy: (1) in
      temporal lobe epilepsy, epilepsy surgery yielded 48.9% of life expectancy years
      in seizure freedom while medical treatment yielded 14.3%; and (2) in
      extratemporal epilepsy, epilepsy surgery yielded 43.0% of life expectancy years
      in seizure freedom while medical treatment yielded 14.3%. SIGNIFICANCE: Epilepsy
      surgery yields a substantially higher life expectancy than continued medical
      treatment for surgically eligible children with refractory epilepsy. This
      conclusion remains robust across a wide range of parameter variations.

PMID- 25599895
TI  - Improving rice tolerance to potassium deficiency by enhancing OsHAK16p:WOX11
      controlled root development.
AB  - Potassium (K) deficiency in plants confines root growth and decreases root-to
      shoot ratio, thus limiting root K acquisition in culture medium. A WUSCHEL
      related homeobox (WOX) gene, WOX11, has been reported as an integrator of auxin
      and cytokinin signalling that regulates root cell proliferation. Here, we report
      that ectopic expression of WOX11 gene driven by the promoter of OsHAK16 encoding
      a low-K-enhanced K transporter led to an extensive root system and adventitious
      roots and more effective tiller numbers in rice. The WOX11-regulated root and
      shoot phenotypes in the OsHAK16p:WOX11 transgenic lines were supported by K
      deficiency-enhanced expression of several RR genes encoding type-A cytokinin
      responsive regulators, PIN genes encoding auxin transporters and Aux/IAA genes.
      In comparison with WT, the transgenic lines showed increases in root biomass,
      root activity and K concentrations in the whole plants, and higher soluble sugar
      concentrations in roots particularly under low K supply condition. The
      improvement of sugar partitioning to the roots by the expression of
      OsHAK16p:WOX11 was further indicated by increasing the expression of OsSUT1 and
      OsSUT4 genes in leaf blades and several OsMSTs genes in roots. Expression of
      OsHAK16p:WOX11 in the rice grown in moderate K-deficient soil increased total K
      uptake by 72% and grain yield by 24%-32%. The results suggest that enlarging root
      growth and development by the expression of WOX11 in roots could provide a useful
      option for increasing K acquisition efficiency and cereal crop productivity in
      low K soil. 

PMID- 25599897
TI  - Hydrated nucleus pulposus herniation in seven dogs.
AB  - The clinical signs, magnetic resonance imaging (MRI) findings, treatment and
      follow-up in seven dogs with hydrated nucleus pulposus extrusion (HNPE) are
      reported. All dogs had tetraparesis or tetraplegia. T2-weighted MRI revealed
      extradural hyperintense homogeneous material compressing the cervical spinal
      cord. After conservative treatment (five dogs) or surgical decompression (two
      dogs), all dogs returned to ambulatory function within 1 month. Follow-up MRI in
      conservatively treated dogs revealed complete disappearance of the extruded
      material. Histopathological examination of surgical specimens confirmed that the
      retrieved material was extruded nucleus pulposus with evidence of early
      degeneration. 

PMID- 25599898
TI  - A blind insertion airway device in dogs as an alternative to traditional
      endotracheal intubation.
AB  - Endotracheal intubation is the standard of care to establish a secure airway;
      however, laryngeal airway management systems are increasingly being used in human
      patients for elective surgical procedures and in emergency settings. In this
      study, a double lumen, blind insertion airway device (BIAD) was placed in the
      esophagus of dogs and evaluated for its ability to ventilate the lungs.
      Initially, 10 euthanazed dogs were evaluated, followed by a group of 15 mixed
      breed dogs that were undergoing elective spay or neuter procedures, and a group
      of 10 healthy dogs. Post-procedure evaluation included visual examination with a
      laryngoscope to inspect for signs of inflammation or mucosal damage. The device
      provided adequate ventilation in all subjects; the dogs were under anesthesia or
      heavily sedated for 10 min to 2 h and recovered uneventfully. No evidence of
      esophagitis, aspiration pneumonia, tracheitis, subcutaneous emphysema or
      esophageal laceration was observed. In conclusion, the use of double lumen airway
      devices warrants further study as an alternative airway management system in
      dogs.

PMID- 25599899
TI  - Effect of dystocia and treatment with oxytocin on neonatal calf vitality and acid
      base, electrolyte and haematological status.
AB  - Under adverse obstetrical conditions, appropriate supervision and assistance
      during the immediate neonatal period are of the utmost importance, especially for
      weak calves. The aim of this study was to establish the effects of dystocia and
      oxytocin infusion on neonatal vitality, acid-base balance, and electrolyte and
      haematological homeostasis of dairy calves. Data were collected for 30 Holstein
      calves which were allocated to three groups: normal calving (n = 10); dystocia
      with mild to severe obstetric assistance (n = 10); and uterine inertia treated
      with oxytocin (n = 10). All 30 calves exhibited normothermia at birth, but had a
      significant decrease in body temperature after 60 min. Dystocic calves had lower
      Apgar scores than calves in the other two groups, and had respiratory and
      metabolic acidosis. Calves from normal calvings had normal blood pH, but base
      excess below the reference range. The mean partial pressure (Pa) of oxygen of
      calves whose dam had been treated with oxytocin was lower than that of calves
      from normal calvings. In all experimental groups, there was improvement in
      metabolic status in the first 60 min postpartum as PaCO2 values significantly
      decreased. All calves had normonatraemia, normokalaemia and normochloridaemia
      during the study period, but calves born to dams treated with oxytocin had a
      higher sodium concentration than those in the two other groups.

PMID- 25599901
TI  - Stem cell therapy in the horse: from laboratory to clinic.

PMID- 25599900
TI  - Serotonin markers show altered transcription levels in an experimental pig model
      of mitral regurgitation.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the
      pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor
      (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased
      tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter
      (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased
      clearance have been suggested. It remains unknown how haemodynamic changes
      associated with mitral regurgitation (MR) affect 5-HT markers in the mitral
      valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced
      MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild
      MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5
      HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR
      (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left
      ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in
      relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs
      were up-regulated in MV compared to AP and LV (P <0.01). In contrast, SERT and
      TPH-1 were up-regulated in AP and LV compared to MV (P <0.05). In MV, mRNA levels
      were increased for 5-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) in sMR
      vs. CON. There were no group differences in 5-HT2BR staining (IHC) but co
      localisation was found with alpha-SMA-positive cells in 91% of all valves and
      with 33% of histological lesions. In LV, 5-HT1BR mRNA levels were increased in
      sMR vs. CON (P = 0.01). In conclusion, these data suggest that MR may affect mRNA
      expression of valvular 5-HT2BR and SERT, and left ventricular 5-HT1BR in some
      pigs.

PMID- 25599902
TI  - Trends in prevalence, incidence and pharmacologic management of diabetes mellitus
      among seniors newly admitted to long-term care facilities in Saskatchewan between
      2003 and 2011.
AB  - OBJECTIVE: We aimed to describe trends in the prevalence and incidence of
      diabetes mellitus and also report the overall use of diabetes medications among
      patients newly admitted to a long-term care facility (LTCF). METHODS: A
      retrospective cohort study was done using health administrative databases in
      Saskatchewan. Eligible patients were newly admitted to LTCF in Saskatchewan
      between 2003 and 2011 and maintained LTCF residency for at least 6 months.
      Prevalence of diabetes was defined with physician or hospital claims in the 2
      years preceding admission. Antihyperglycemic medication use was estimated from
      prescription claims data during the first 6 months after LTCF admission. All data
      were descriptively analyzed. RESULTS: The validated case definition for diabetes
      (>=2 diagnostic claims) in the 2 years before or 6 months after admission was met
      by 16.9% of patients (2471 of 14,624). An additional 965 patients (6.6%) had a
      single diabetes diagnostic claim or antihyperglycemic prescriptions only. Among
      patients receiving antihyperglycemic therapies, 64.9% (1518 of 2338) were
      exclusively managed with oral medications, and metformin was the most commonly
      used medication. Glyburide was commonly withdrawn after LTCF admission. Insulin
      use was observed in 23.9% of diabetes patients, with a mean daily average
      consumption of 54.7 units per day. CONCLUSIONS: Use of diabetes medications
      appear to generally align with Canadian practice recommendations as evidenced by
      declining use of glyburide and frequent use of metformin. Future studies should
      examine clinical benefits and safety of hypoglycemic agent use in LTCFs.

PMID- 25599903
TI  - Adenomyosis: a life-cycle approach.
AB  - The life-cycle approach to endometriosis highlighted unexpected features of the
      condition; the same approach was therefore applied to gain insight into the
      clinical features of adenomyosis and to draw a comparison with endometriosis.
      This is possible today thanks to new imaging techniques enabling non-invasive
      diagnosis of adenomyosis. The specificity and sensitivity of magnetic resonance
      imaging and transvaginal ultrasound remain uncertain. Unlike endometriosis,
      little information is available on the presence of classic adenomyosis in
      adolescents, except for rare cystic forms that may not represent the true
      disease. Adenomyosis is most likely to affect adult women, although most reported
      incidences are still based on post-hysterectomy studies, and are affected by
      diligence in histopathologic diagnosis and the adopted cut-off point. The
      traditionally accepted associations of adult adenomyosis, such as multiparity, a
      link to infertility and its effect on pregnancy are uncertain. Active adenomyosis
      has been found in pre- and peri-menopausal women and in postmenopausal women
      receiving tamoxifen. In conclusion, major diagnostic limitations and the
      systematic bias of hysterectomy make it difficult to draw firm conclusions from
      existing evidence. In addition, no information is available on the natural
      history of adenomyosis and no study has systematically evaluated its existence in
      adolescents. 

PMID- 25599906
TI  - Connecting the dots: bridging patient and population health data systems.

PMID- 25599905
TI  - Violence and cardiovascular health: a systematic review.
AB  - CONTEXT: Violence, experienced in either childhood or adulthood, has been
      associated with physical health outcomes, including cardiovascular disease.
      However, the consistency of the existing literature has not been evaluated.
      EVIDENCE ACQUISITION: In 2013, the authors conducted a PubMed and Web of Science
      review of peer-reviewed articles published prior to August 2013 on the relation
      between violence exposure, experienced in either childhood or adulthood, and
      cardiovascular outcomes. To meet inclusion criteria, articles had to present
      estimates for the relation between violence exposure and cardiovascular outcomes
      (e.g., hypertension, blood pressure, stroke, coronary disease, or myocardial
      infarction) adjusted for demographic factors. Articles focusing on violence from
      television, video games, natural disasters, terrorism, or war were excluded.
      EVIDENCE SYNTHESIS: The initial search yielded 2,273 articles; after removing
      duplicates and applying inclusion and exclusion criteria, 30 articles were
      selected for review. A consistent positive relation was noted on the association
      between violence experienced during childhood and cardiovascular outcomes in
      adulthood (i.e., hypertension, coronary heart disease, and myocardial
      infarction). Associations across genders with varying types of violence exposure
      were also noted. By contrast, findings were mixed on the relation between adult
      violence exposure and cardiovascular outcome. CONCLUSIONS: Despite varying
      definitions of violence exposure and cardiovascular endpoints, a consistent
      relation exists between childhood violence exposure, largely assessed
      retrospectively, and cardiovascular endpoints. Findings are mixed for the adult
      violence-cardiovascular health relation. The cross-sectional nature of most adult
      studies and the reliance of self-reported outcomes can potentially be attributed
      to the lack of findings among adult violence exposure studies.

PMID- 25599904
TI  - Enhancing Web-based mindfulness training for mental health promotion with the
      health action process approach: randomized controlled trial.
AB  - BACKGROUND: With increasing evidence demonstrating the effectiveness of Web-based
      interventions and mindfulness-based training in improving health, delivering
      mindfulness training online is an attractive proposition. OBJECTIVE: The aim of
      this study was to evaluate the efficacy of two Internet-based interventions
      (basic mindfulness and Health Action Process Approach enhanced mindfulness) with
      waitlist control. Health Action Process Approach (HAPA) principles were used to
      enhance participants' efficacy and planning. METHODS: Participants were recruited
      online and offline among local universities; 321 university students and staff
      were randomly assigned to three conditions. The basic and HAPA-enhanced groups
      completed the 8-week fully automated mindfulness training online. All
      participants (including control) were asked to complete an online questionnaire
      pre-program, post-program, and at 3-month follow-up. RESULTS: Significant group
      by time interaction effect was found. The HAPA-enhanced group showed
      significantly higher levels of mindfulness from pre-intervention to post
      intervention, and such improvement was sustained at follow-up. Both the basic and
      HAPA-enhanced mindfulness groups showed better mental well-being from pre
      intervention to post-intervention, and improvement was sustained at 3-month
      follow-up. CONCLUSIONS: Online mindfulness training can improve mental health. An
      online platform is a viable medium to implement and disseminate evidence-based
      interventions and is a highly scalable approach to reach the general public.
      TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC
      12002954; http://www.chictr.org/en/proj/show.aspx?proj=3904 (Archived by WebCite
      at http://www.webcitation.org/6VCdG09pA).

PMID- 25599908
TI  - Editorial: utility and pitfalls of Fatty Liver Index in epidemiologic studies for
      the diagnosis of NAFLD.

PMID- 25599907
TI  - Electronic health records and community health surveillance of childhood obesity.
AB  - BACKGROUND: Childhood obesity remains a public health concern, and tracking local
      progress may require local surveillance systems. Electronic health record data
      may provide a cost-effective solution. PURPOSE: To demonstrate the feasibility of
      estimating childhood obesity rates using de-identified electronic health records
      for the purpose of public health surveillance and health promotion. METHODS: Data
      were extracted from the Public Health Information Exchange (PHINEX) database.
      PHINEX contains de-identified electronic health records from patients primarily
      in south central Wisconsin. Data on children and adolescents (aged 2-19 years,
      2011-2012, n=93,130) were transformed in a two-step procedure that adjusted for
      missing data and weighted for a national population distribution. Weighted and
      adjusted obesity rates were compared to the 2011-2012 National Health and
      Nutrition Examination Survey (NHANES). Data were analyzed in 2014. RESULTS: The
      weighted and adjusted obesity rate was 16.1% (95% CI=15.8, 16.4). Non-Hispanic
      white children and adolescents (11.8%, 95% CI=11.5, 12.1) had lower obesity rates
      compared to non-Hispanic black (22.0%, 95% CI=20.7, 23.2) and Hispanic (23.8%,
      95% CI=22.4, 25.1) patients. Overall, electronic health record-derived point
      estimates were comparable to NHANES, revealing disparities from preschool onward.
      CONCLUSIONS: Electronic health records that are weighted and adjusted to account
      for intrinsic bias may create an opportunity for comparing regional disparities
      with precision. In PHINEX patients, childhood obesity disparities were measurable
      from a young age, highlighting the need for early intervention for at-risk
      children. The electronic health record is a cost-effective, promising tool for
      local obesity prevention efforts.

PMID- 25599910
TI  - Simultaneous determination of insulin and its analogues in pharmaceutical
      formulations by micellar electrokinetic chromatography.
AB  - A simple and efficient MEKC method was developed to simultaneously determine
      human insulin, its five analogues, the main degradation products and the
      excipients usually present in injection formulations. A very fast method with a
      total analysis time of 3 min was then successfully validated for the analysis of
      human insulin and the quality control of commercial formulations was carried out.

PMID- 25599909
TI  - Use of the satisfaction with amplification in daily life questionnaire to assess
      patient satisfaction following remote hearing aid adjustments (telefitting).
AB  - BACKGROUND: Hearing loss can affect approximately 15% of the pediatric population
      and up to 40% of the adult population. The gold standard of treatment for hearing
      loss is amplification of hearing thresholds by means of a hearing aid instrument.
      A hearing aid is an electronic device equipped with a topology of only three
      major components of aggregate cost. The gold standard of hearing aid fittings is
      face-to-face appointments in hearing aid centers, clinics, or hospitals.
      Telefitting encompasses the programming and adjustments of hearing aid settings
      remotely. Fitting hearing aids remotely is a relatively simple procedure, using
      minimal computer hardware and Internet access. OBJECTIVE: This project aimed to
      examine the feasibility and outcomes of remote hearing aid adjustments
      (telefitting) by assessing patient satisfaction via the Portuguese version of the
      Satisfaction With Amplification in Daily Life (SADL) questionnaire. METHODS: The
      Brazilian Portuguese version of the SADL was used in this experimental research
      design. Participants were randomly selected through the Rehabilitation Clinical
      (Espaco Reouvir) of the Otorhinolaryngology Department Medical School University
      of Sao Paulo. Of the 8 participants in the study, 5 were female and 3 were male,
      with a mean age of 71.5 years. The design consisted of two face-to-face sessions
      performed within 15 working days of each other. The remote assistance took place
      15 days later. RESULTS: The average scores from this study are above the mean
      scores from the original SADL normative data. These indicate a high level of
      satisfaction in participants who were fitted remotely. CONCLUSIONS: The use of an
      evaluation questionnaire is a simple yet effective method to objectively assess
      the success of a remote fitting. Questionnaire outcomes can help hearing
      stakeholders improve the National Policy on Hearing Health Care in Brazil. The
      results of this project indicated that patient satisfaction levels of those
      fitted remotely were comparable to those fitted in the conventional manner, that
      is, face-to-face.

PMID- 25599911
TI  - Impact of intraventricular hemorrhage measured by Graeb and LeRoux score on case
      fatality risk and chronic hydrocephalus in aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Reliable prognostic tools to estimate the case fatality rate (CFR)
      and the development of chronic hydrocephalus (CHC) in aneurysmal subarachnoid
      hemorrhage (SAH) are not well defined. This study aims to investigate the
      practicability and reliability of Fisher, Graeb, and LeRoux scores for SAH
      patient prognosis. METHODS: A total of 206 patients with aneurysmal SAH were
      retrospectively analyzed in prediction of CFR and CHC. Clinical data was
      evaluated and grading was performed using Fisher, Graeb, and LeRoux scores.
      Univariate and multivariate analyses were performed to identify relevant
      predictive parameters. RESULTS: CFR was 17.0 % and was associated with higher
      age, higher Hunt & Hess (H&H) grade, lower Glasgow Coma Scale (GCS) at admission,
      as well as a higher Fisher, Graeb, and LeRoux score (p < 0.001). There were 19.9
      % that developed CHC requiring permanent cerebrospinal fluid diversion. Low
      initial GCS (p = 0.003), high H&H (p < 0.001), intracerebral hematoma (p =
      0.003), high Fisher (p = 0.047), Graeb and LeRoux scores (p < 0.001) were
      associated with a higher rate of ventricular-peritoneal shunting (VPS) in
      surviving patients. In multivariate analyses, Graeb score (odds ratio (OR) 1.183
      [1.027, 1.363], p = 0.020), LeRoux score (OR 1.120 [1.013-1.239, p = 0.027), and
      H&H (OR 2.715 [1.496, 4.927], p = 0.001) remained independent prognostic factors
      for VPS. CONCLUSIONS: Graeb or LeRoux scores improve the prediction of shunt
      dependency and in parts of CFR in aneurysmal SAH patients therefore confirming
      the relevance of the extent and distribution of intraventricular blood for the
      clinical course in SAH.

PMID- 25599912
TI  - Inclusion body myositis and sarcoid myopathy: coincidental occurrence or
      associated diseases.
AB  - Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy
      characterized by selective weakness of finger flexors and quadriceps muscles
      commonly refractory to treatment. Another chronic inflammatory disorder,
      sarcoidosis, commonly involves muscle. The comorbidity of inclusion body myositis
      and sarcoid myopathy is rare. We describe clinical and muscle biopsy findings of
      a patient with sarcoidosis and inclusion body myositis. A 66-year-old man
      presented with a 6-year history of progressive, asymmetrical and selective
      weakness of the quadriceps, biceps and finger flexor muscles; he had a remote
      history of pulmonary sarcoidosis. A quadriceps muscle biopsy revealed a chronic
      inflammatory myopathy with ubiquitinated inclusion bodies, rimmed vacuoles,
      expression of major histocompatibility complex class I, numerous COX-negative
      fibers and TDP-43 cytoplasmic aggregates (features of IBM) and multiple non
      necrotizing granulomata (feature of sarcoidosis). Clinical and histopathologic
      features of the current illness suggested the patient had sarcoidosis with
      inclusion body myositis overlap. This patient may represent the coincidental
      occurrence of both idiopathic inflammatory disorders. Alternatively, sarcoidoisis
      may promote the development of inclusion body myositis by a similar immune
      mediated pathophysiologic process. 

PMID- 25599914
TI  - Slow recovery of High Arctic heath communities from nitrogen enrichment.
AB  - Arctic ecosystems are strongly nutrient limited and exhibit dramatic responses to
      nitrogen (N) enrichment, the reversibility of which is unknown. This study
      uniquely assesses the potential for tundra heath to recover from N deposition and
      the influence of phosphorus (P) availability on recovery. We revisited an
      experiment in Svalbard, established in 1991, in which N was applied at rates
      representing atmospheric N deposition in Europe (10 and 50 kg N ha(-1)  yr(-1) ;
      'low' and 'high', respectively) for 3-8 yr. We investigated whether significant
      effects on vegetation composition and ecosystem nutrient status persisted up to
      18 yr post-treatment. Although the tundra heath is no longer N saturated, N
      treatment effects persist and are strongly P-dependent. Vegetation was more
      resilient to N where no P was added, although shrub cover is still reduced in low
      N plots. Where P was also added (5 kg P ha(-1)  yr(-1) ), there are still effects
      of low N on community composition and nutrient dynamics. High N, with and without
      P, has many lasting impacts. Importantly, N + P has caused dramatically increased
      moss abundance, which influences nutrient dynamics. Our key finding is that
      Arctic ecosystems are slow to recover from even small N inputs, particularly
      where P is not limiting. 

PMID- 25599915
TI  - Interplay of relativistic and nonrelativistic transport in atomically precise
      segmented graphene nanoribbons.
AB  - Graphene's isolation launched explorations of fundamental relativistic physics
      originating from the planar honeycomb lattice arrangement of the carbon atoms,
      and of potential technological applications in nanoscale electronics. Bottom-up
      fabricated atomically-precise segmented graphene nanoribbons, SGNRs, open avenues
      for studies of electrical transport, coherence, and interference effects in
      metallic, semiconducting, and mixed GNRs, with different edge terminations.
      Conceptual and practical understanding of electric transport through SGNRs is
      gained through nonequilibrium Green's function (NEGF) conductance calculations
      and a Dirac continuum model that absorbs the valence-to-conductance energy gaps
      as position-dependent masses, including topological-in-origin mass-barriers at
      the contacts between segments. The continuum model reproduces the NEGF results,
      including optical Dirac Fabry-Prot (FP) equidistant oscillations for massless
      relativistic carriers in metallic armchair SGNRs, and an unequally-spaced FP
      pattern for mixed armchair-zigzag SGNRs where carriers transit from a
      relativistic (armchair) to a nonrelativistic (zigzag) regime. This provides a
      unifying framework for analysis of coherent transport phenomena and
      interpretation of forthcoming experiments in SGNRs. 

PMID- 25599916
TI  - A molecular pathway for CO2 response in Arabidopsis guard cells.
AB  - Increasing carbon dioxide (CO2) levels in the atmosphere have caused global
      metabolic changes in diverse plant species. CO2 is not only a carbon donor for
      photosynthesis but also an environmental signal that regulates stomatal movements
      and thereby controls plant-water relationships and carbon metabolism. However,
      the mechanism underlying CO2 sensing in stomatal guard cells remains unclear.
      Here we report characterization of Arabidopsis RESISTANT TO HIGH CO2 (RHC1), a
      MATE-type transporter that links elevated CO2 concentration to repression of HT1,
      a protein kinase that negatively regulates CO2-induced stomatal closing. We also
      show that HT1 phosphorylates and inactivates OST1, a kinase which is essential
      for the activation of the SLAC1 anion channel and stomatal closing. Combining
      genetic, biochemical and electrophysiological evidence, we reconstituted the
      molecular relay from CO2 to SLAC1 activation, thus establishing a core pathway
      for CO2 signalling in plant guard cells.

PMID- 25599917
TI  - Metabolism gene signatures and surgical site infections in abdominal surgery.
AB  - INTRODUCTION: Surgical site infections (SSI) represent a significant cause of
      morbidity in abdominal surgery. The objective of this study was to determine the
      gene expression signature in subcutaneous tissues in relation to SSI. METHODS: To
      determine differences in gene expression, microarray analysis were performed from
      bulk tissue mRNA of subcutaneous tissues prospectively collected in 92 patients
      during open abdominal surgery. 10 patients (11%) developed incisional
      (superficial and deep) SSI. RESULTS: Preoperative risk factors in patients with
      SSI were not significantly different from those in patients without wound
      infections. 1025 genes were differentially expressed between the groups, of which
      the AZGP1 and ALDH1A3 genes were the highest down- and upregulated ones.
      Hierarchical clustering demonstrated strong similarity within the respective
      groups (SSI vs. no-SSI) indicating inter-group distinctness. In a functional
      classification, genes controlling cell metabolism were mostly down-regulated in
      subcutaneous tissues of patients that subsequently developed SSI. CONCLUSION:
      Altered expression of metabolism genes in subcutaneous tissues might constitute a
      risk factor for postoperative abdominal SSI.

PMID- 25599918
TI  - Beyond central adiposity: liver fat and visceral fat area are associated with
      metabolic syndrome in morbidly obese patients.
AB  - BACKGROUND: Despite its widespread clinical use, both body mass index (BMI) and
      waist circumference have been reported as inaccurate methods to measure abdominal
      obesity. The main objective of this study was to determine the relation between
      visceral fat area and fatty liver infiltration with the expression of metabolic
      syndrome (MS) in morbidly obese patients. METHODS: We recruited a random
      selection of 100 morbidly obese patients on pre-operative evaluation for
      bariatric surgery. A pre-operative CT slice at L4-L5 level, was performed to
      measure visceral fat and at T12 level to measure hepatic attenuation. RESULTS:
      Patients with MS had lower hepatic attenuation values (median 49.9 vs 55.5HU; p =
      .018) and had more VAT (242 vs 172 cm(2);p = .001). Conventional measures (BMI: p
      = .729 and waist circumference: p = .356), were not useful in discriminating
      morbidly obese patients with MS. By multivariable logistic regression, fatty
      liver infiltration (OR = 5.3; p = .03) and age (OR = 1.08; p = .04) were the only
      factors independently related to the presence of MS. MS prevalence was 100%, 71%
      and 55%, respectively for patients with both fatty liver and visceral adiposity;
      one; or none of this findings (AUC - .715; p = .016). CONCLUSION: CT scan seems
      to measure 2 important markers of MS: visceral adiposity and hepatic fatty
      infiltration. In morbidly obese patients, both visceral adiposity and hepatic
      fatty infiltration increase the risk for the presence of MS.

PMID- 25599913
TI  - Molecular layer interneurons of the cerebellum: developmental and morphological
      aspects.
AB  - During the past 25 years, our knowledge on the development of basket and stellate
      cells (molecular layer interneurons [MLIs]) has completely changed, not only
      regarding their origin from the ventricular zone, corresponding to the primitive
      cerebellar neuroepithelium, instead of the external granular layer, but above all
      by providing an almost complete account of the genetic regulations (transcription
      factors and other genes) involved in their differentiation and synaptogenesis.
      Moreover, it has been shown that MLIs' precursors (dividing neuroblasts) and not
      young postmitotic neurons, as in other germinal neuroepithelia, leave the
      germinative zone and migrate all along a complex and lengthy path throughout the
      presumptive cerebellar white matter, which provides suitable niches exerting
      epigenetic influences on their ultimate neuronal identities. Recent studies
      carried out on the anatomical-functional properties of adult MLIs emphasize the
      importance of these interneurons in regulating PC inhibition, and point out the
      crucial role played by electrical synaptic transmission between MLIs as well as
      ephaptic interactions between them and Purkinje cells at the pinceaux level, in
      the regulation of this inhibition. 

PMID- 25599919
TI  - A new look at rheumatology in China--opportunities and challenges.
AB  - In the past two decades, Chinese rheumatology has developed rapidly in terms of
      both clinical practice and basic research. Many rheumatology departments and
      divisions have been established, creating positions for more residents to join
      rheumatology practices. Numerous studies of rheumatic diseases have been
      published in recent years by Chinese rheumatologists and immunologists, supported
      by government funding that has dramatically increased over the past few years.
      These studies are focused mainly on epidemiology, mechanisms, early diagnosis and
      interventions of rheumatic diseases. Increasing numbers of national and
      international scientific activities in China, including research collaborations,
      education programmes and conferences have greatly helped the development of
      rheumatology. In this APLAR series article, the major, high-impact studies and
      latest developments in Chinese rheumatology are reviewed. 

PMID- 25599920
TI  - High-resolution peripheral quantitative CT in rheumatology.

PMID- 25599921
TI  - Reply: HR-pQCT has promise in rheumatology.

PMID- 25599922
TI  - Label-free DNA-based detection of Mycobacterium tuberculosis and rifampicin
      resistance through hydration induced stress in microcantilevers.
AB  - We have developed a label-free assay for the genomic detection of Mycobacterium
      tuberculosis and rifampicin resistance. The method relies on the quantification
      of the hydration induced stress on microcantilever biosensors functionalized with
      oligonucleotide probes, before and after hybridization with specific targets. We
      have found a limit of detection of 10 fg/mL for PCR amplified products of 122 bp.
      Furthermore, the technique can successfully target genomic DNA (gDNA) fragments
      of length >500 bp, and it can successfully discriminate single mismatches. We
      have used both loci IS6110 and rpoB as targets to detect the mycobacteria and the
      rifampicin resistance from gDNA directly extracted from bacterial culture and
      without PCR amplification. We have been able to detect 2 pg/mL target
      concentration in samples with an excess of interfering DNA and in a total
      analysis time of 1 h and 30 min. The detection limit found demonstrates the
      capability to develop direct assays without the need for long culture steps or
      PCR amplification. The methodology can be easily translated to different
      microbial targets, and it is suitable for further development of miniaturized
      devices and multiplexed detection. 

PMID- 25599923
TI  - Functional significance of aberrantly expressed microRNAs in prostate cancer.
AB  - microRNAs, a class of small non-coding RNAs, regulate protein-coding gene
      expression by repressing translation or cleaving RNA transcripts in a sequence
      specific manner. A growing body of evidence suggests that microRNAs contribute to
      prostate cancer development, progression and metastasis. Based on reports
      describing microRNA expression signatures, several differentially expressed
      microRNAs have been discovered. In the present review, eight genome-wide microRNA
      expression signatures were used to select aberrantly expressed microRNAs (i.e.
      upregulated and downregulated microRNAs) in prostate cancer clinical specimens.
      Also, we mapped these selected microRNAs in the human genome. Interestingly, some
      clustered microRNAs, such as miR-221/222, miR-143/145, miR-23b/27b/24-1 and miR
      1/133a, are frequently downregulated in cancer tissues, and recent studies have
      shown that these clustered microRNAs function as tumor suppressors. We also
      discuss the functional significance of the differentially expressed microRNAs and
      the molecular pathways/targets regulated by these microRNAs. These recent
      findings of microRNAs in prostate cancer will facilitate the development of
      effective strategies for microRNA-based therapeutics for the treatment of
      prostate cancer. 

PMID- 25599924
TI  - Outcomes of talar dome osteochondral defect repair using osteocartilaginous
      autografts: 37 cases of Mosaicplasty(r).
AB  - BACKGROUND: The indications of osteochondral autograft implantation using the
      Mosaicplasty((r)) technique were only recently extended to osteochondral lesions
      of the talus (OLT), a site for which no medium- or long-term outcome data are
      available. Our objective here was to evaluate medium-term outcomes in case-series
      of patients who underwent Mosaicplasty((r)) for OLT repair. HYPOTHESIS:
      Mosaicplasty((r)) provides good medium-term outcomes with low morbidity when used
      for OLT repair. PATIENTS ET METHODS: We retrospectively reviewed cases of
      Mosaicplasty((r)) for OLT repair, performed in combination with malleolar
      osteotomy on the side of the OLT, at either of two centres, between 1997 and
      2013. Pre-operative clinical data were collected from the medical records and all
      patients were re-evaluated. We studied 37 patients with a mean age of 33 years.
      RESULTS: Mean follow-up at re-evaluation was 76 months. Mean AOFAS score at re
      evaluation was 83 (range, 9-100). A work-related cause to the OLT was associated
      with significantly poorer outcomes (P=0.01). AOFAS values were significantly
      better in patients whose OLT size was 0.5 to 1cm(2). The Ogilvie-Harris score at
      last follow-up was good or excellent in 78% of patients. No patient experienced
      morbidity related to the malleolar osteotomy. Persistent patellar syndrome was
      noted in 6 patients. DISCUSSION: In our case-series, Mosaicplasty((r)) for OLT
      repair provided good medium-term outcomes in 78% of patients. Nevertheless, the
      donor-site morbidity should be borne in mind. Mosaicplasty((r)) deserves to be
      viewed as a reference standard method for OLT repair. LEVEL OF EVIDENCE: IV,
      retrospective study.

PMID- 25599926
TI  - The intrinsic operation of the networks that make us locomote.
AB  - The spinal cord of all vertebrates contains the networks that coordinate the
      locomotor movements. In lamprey, zebrafish and amphibian tadpoles these networks
      generate the swimming movements and depend primarily on ipsilateral excitatory
      premotor interneurons of the V2a type (zebrafish) generate the segmental burst
      pattern. In zebrafish they can be further subdivided into three subclasses
      activating slow, intermediate and fast muscle fibers. Inhibitory commissural
      neurons are responsible for the alternating pattern between the two sides of the
      body. Stretch receptor neurons sense the movements and provide sensory feedback.
      In mammals the locomotor pattern in each limb comprises four different phases
      including flexor-extensor alternation. Also in this case local ipsilateral
      excitatory V2 interneurons can drive rhythmic burst activity in individual muscle
      groups. The coordination between the two hind limbs appears to be controlled by
      separate sets of commissural interneurons (V0) most likely engaged in walk, trot
      and gallop respectively. 

PMID- 25599925
TI  - Effects of meal variety on expected satiation: evidence for a 'perceived volume'
      heuristic.
AB  - Meal variety has been shown to increase energy intake in humans by an average of
      29%. Historically, research exploring the mechanism underlying this effect has
      focused on physiological and psychological processes that terminate a meal (e.g.,
      sensory-specific satiety). We sought to explore whether meal variety stimulates
      intake by influencing pre-meal planning. We know that individuals use prior
      experience with a food to estimate the extent to which it will deliver fullness.
      These 'expected satiation' judgments may be straightforward when only one meal
      component needs to be considered, but it remains unclear how prospective
      satiation is estimated when a meal comprises multiple items. We hypothesised that
      people simplify the task by using a heuristic, or 'cognitive shortcut.'
      Specifically, as within-meal variety increases, expected satiation tends to be
      based on the perceived volume of food(s) rather than on prior experience. In each
      trial, participants (N = 68) were shown a plate of food with six buffet food
      items. Across trials the number of different foods varied in the range one to
      six. In separate tasks, the participants provided an estimate of their combined
      expected satiation and volume. When meal variety was high, judgments of perceived
      volume and expected satiation 'converged.' This is consistent with a common
      underlying response strategy. By contrast, the low variety meals produced
      dissociable responses, suggesting that judgments of expected satiation were not
      governed solely by perceived volume. This evidence for a 'volume heuristic' was
      especially clear in people who were less familiar with the meal items. Together,
      these results are important because they expose a novel process by which meal
      variety might increase food intake in humans. 

PMID- 25599927
TI  - Incidence of cancer in children aged 0-14 years in Taiwan, 1996-2010.
AB  - Studies have found lower risk of childhood cancer among Asian children. We aim to
      characterize the recent incidence and incidence-trend of childhood cancer in
      Taiwan after the National Health Insurance program was launched in March 1995.
      Data were extracted from the Taiwan Cancer Registry, a population-based database
      established in 1979. Cases diagnosed at age 0-14 from 1996 to 2010 were analyzed
      and categorized according to the International Classification of Childhood
      Cancer, Third Edition (ICCC-3). In total, 8032 childhood cancer cases were
      included, with a microscopic verification rate of 93.9%. The overall age
      standardized rate (ASR) of incidence adjusted to the 2000 World Standard
      Population is 125.0 cases/million, with a male-to-female ratio of 1.3. The top
      five cancer types (ICCC-3 subgroup[s]; ASR per million) are acute lymphoblastic
      leukemia (Ia, 30.3), acute myeloid leukemia (Ib; 9.4), non-Hodgkin lymphoma
      (IIb,c,e, 9.0), extracranial germ cell tumor (Xb,c; 8.3), and neuroblastoma (IVa;
      7.8). The median age of diagnosis was 6 years for both genders. During the study
      period, the ASR of childhood cancer has been increasing at a rate of 1.2% per
      year (95% confidence interval, 0.6-1.7%). In contrast to Western countries,
      China, Japan, and Taiwan have lower incidence of childhood cancer; however,
      Taiwan's incidence rates of childhood germ cell tumors and hepatic tumors are
      higher. In conclusion, this population-based study reveals that the incidence
      rate of childhood cancer in Taiwan is rising consistently. The high incidence of
      germ cell tumors warrants further investigation. 

PMID- 25599928
TI  - Spinal deformity progression after posterior segmental instrumentation and fusion
      for idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective chart and radiographic review. PURPOSE: To assess the
      incidence of and variables associated with spinal deformity progression after
      posterior segmental instrumentation and fusion at a single institution.
      Progression of the scoliotic deformity after posterior instrumented spinal fusion
      has been described. Recent studies have concluded that segmental pedicle screw
      constructs are better able to control deformity progression. METHODS:
      Retrospective review of a consecutive series of idiopathic scoliosis patients (n
      = 89) with major thoracic curves (Lenke types 1-4) treated with posterior
      segmental instrumentation and fusion. Deformity progression was defined as a 10
      degrees  increase in Cobb angle between the first-erect and 2-year post-operative
      radiographs. Clinical and radiographic data between the two cohorts (deformity
      progression versus stable) were analyzed to determine the variables associated
      with deformity progression. RESULTS: Patients in the deformity progression group
      (n = 13) tended to be younger (median 13.7 vs. 14.7 years) and experienced a
      significant change in height (p = 0.01) during the post-operative period compared
      to the stable group (n = 76). At 2-years post-op, the patients in the deformity
      progression group had experienced a significantly greater change in upper
      instrumented vertebra (UIV) angulation, lower instrumented vertebra (LIV)
      angulation, and apical vertebral translation (AVT). Two-year post-op Scoliosis
      Research Society questionnaire (SRS-22) scores in the appearance domain were also
      significantly worse in the deformity progression group. Patients in the deformity
      progression group had a significantly greater difference between the lowest
      instrumented vertebra and stable vertebra compared to patients in the stable
      group (p = 0.001). CONCLUSIONS: Deformity progression after posterior spinal
      fusion does occur after modern segmental instrumentation. Segmental pedicle screw
      constructs do not prevent deformity progression. Skeletally immature patients
      with a significant growth potential are at the highest risk for deformity
      progression. In immature patients, extending the fusion distally to the stable
      vertebra may minimize deformity progression. LEVEL OF EVIDENCE: Level III.

PMID- 25599929
TI  - Effect of a moustache on nasal Staphylococcus aureus colonisation and nasal
      cytology results in men.
AB  - OBJECTIVE: This study compared the results of nasal Staphylococcus aureus
      carriage and nasal cytology in men with and without a moustache. METHODS: The
      study group comprised 118 adult men with a moustache, and the control group
      consisted of 123 adult men without a moustache. Samples were taken from the
      participants' right nasal cavity for cytology and from the left nasal cavity for
      microbiology. RESULTS: The results for S aureus were positive in 19.5 per cent (n
      = 23) of participants with a moustache and in 20.3 per cent (n = 25) of men
      without a moustache. This difference was not significant (p > 0.05). However,
      nasal cytology revealed rich eosinophil clusters in participants with a
      moustache. CONCLUSION: The presence or absence of a moustache had no effect on
      nasal S aureus colonisation. However, further research is needed to understand
      whether the presence of a moustache increases the risk of allergic or non
      allergic rhinitis.

PMID- 25599930
TI  - An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in
      Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and
      Autism.
AB  - BACKGROUND: Mutations of MAGEL2 have been reported in patients presenting with
      autism, and loss of MAGEL2 is also associated with Prader-Willi syndrome, a
      neurodevelopmental genetic disorder. This study aimed to determine the behavioral
      phenotype of Magel2-deficient adult mice, to characterize the central oxytocin
      (OT) system of these mutant mice, and to test the curative effect of a peripheral
      OT treatment just after birth. METHODS: We assessed the social and cognitive
      behavior of Magel2-deficient mice, analyzed the OT system of mutant mice treated
      or not by a postnatal administration of OT, and determined the effect of this
      treatment on the brain. RESULTS: Magel2 inactivation induces a deficit in social
      recognition and social interaction and a reduced learning ability in adult male
      mice. In these mice, we reveal anatomical and functional modifications of the OT
      system and show that these defects change from birth to adulthood. Daily
      administration of OT in the first postnatal week was sufficient to prevent
      deficits in social behavior and learning abilities in adult mutant male mice. We
      show that this OT treatment partly restores a normal OT system. Thus, we report
      that an alteration of the OT system around birth has long-term consequences on
      behavior and on cognition. Importantly, an acute OT treatment of Magel2-deficient
      pups has a curative effect. CONCLUSIONS: Our study reveals that OT plays a
      crucial role in setting social behaviors during a period just after birth. An
      early OT treatment in this critical period could be a novel therapeutic approach
      for the treatment of neurodevelopmental disorders such as Prader-Willi syndrome
      and autism.

PMID- 25599932
TI  - Disadvantages of using the area under the receiver operating characteristic curve
      to assess imaging tests: a discussion and proposal for an alternative approach.
AB  - OBJECTIVES: The objectives are to describe the disadvantages of the area under
      the receiver operating characteristic curve (ROC AUC) to measure diagnostic test
      performance and to propose an alternative based on net benefit. METHODS: We use a
      narrative review supplemented by data from a study of computer-assisted detection
      for CT colonography. RESULTS: We identified problems with ROC AUC. Confidence
      scoring by readers was highly non-normal, and score distribution was bimodal.
      Consequently, ROC curves were highly extrapolated with AUC mostly dependent on
      areas without patient data. AUC depended on the method used for curve fitting.
      ROC AUC does not account for prevalence or different misclassification costs
      arising from false-negative and false-positive diagnoses. Change in ROC AUC has
      little direct clinical meaning for clinicians. An alternative analysis based on
      net benefit is proposed, based on the change in sensitivity and specificity at
      clinically relevant thresholds. Net benefit incorporates estimates of prevalence
      and misclassification costs, and it is clinically interpretable since it reflects
      changes in correct and incorrect diagnoses when a new diagnostic test is
      introduced. CONCLUSIONS: ROC AUC is most useful in the early stages of test
      assessment whereas methods based on net benefit are more useful to assess
      radiological tests where the clinical context is known. Net benefit is more
      useful for assessing clinical impact. KEY POINTS: * The area under the receiver
      operating characteristic curve (ROC AUC) measures diagnostic accuracy. *
      Confidence scores used to build ROC curves may be difficult to assign. * False
      positive and false-negative diagnoses have different misclassification costs. *
      Excessive ROC curve extrapolation is undesirable. * Net benefit methods may
      provide more meaningful and clinically interpretable results than ROC AUC.

PMID- 25599931
TI  - Pharmacological inhibition of BACE1 impairs synaptic plasticity and cognitive
      functions.
AB  - BACKGROUND: BACE1 (beta site amyloid precursor protein cleaving enzyme 1) is the
      rate limiting protease in amyloid beta production, hence a promising drug target
      for the treatment of Alzheimer's disease. Inhibition of BACE1, as the major beta
      secretase in vivo with multiple substrates, however is likely to have mechanism
      based adverse effects. We explored the impact of long-term pharmacological
      inhibition of BACE1 on dendritic spine dynamics, synaptic functions, and
      cognitive performance of adult mice. METHODS: Sandwich enzyme-linked
      immunosorbent assay was used to assess Abeta40 levels in brain and plasma after
      oral administration of BACE1 inhibitors SCH1682496 or LY2811376. In vivo two
      photon microscopy of the somatosensory cortex was performed to monitor structural
      dynamics of dendritic spines while synaptic functions and plasticity were
      measured via electrophysiological recordings of excitatory postsynaptic currents
      and hippocampal long-term potentiation in brain slices. Finally, behavioral tests
      were performed to analyze the impact of pharmacological inhibition of BACE1 on
      cognitive performance. RESULTS: Dose-dependent decrease of Abeta40 levels in vivo
      confirmed suppression of BACE1 activity by both inhibitors. Prolonged treatment
      caused a reduction in spine formation of layer V pyramidal neurons, which
      recovered after withdrawal of inhibitors. Congruently, the rate of spontaneous
      and miniature excitatory postsynaptic currents in pyramidal neurons and
      hippocampal long-term potentiation were reduced in animals treated with BACE1
      inhibitors. These effects were not detected in Bace1(-/-) mice treated with
      SCH1682496, confirming BACE1 as the pharmacological target. Described structural
      and functional changes were associated with cognitive deficits as revealed in
      behavioral tests. CONCLUSIONS: Our findings indicate important functions to BACE1
      in structural and functional synaptic plasticity in the mature brain, with
      implications for cognition.

PMID- 25599933
TI  - Assessment of image quality in soft tissue and bone visualization tasks for a
      dedicated extremity cone-beam CT system.
AB  - OBJECTIVE: To assess visualization tasks using cone-beam CT (CBCT) compared to
      multi-detector CT (MDCT) for musculoskeletal extremity imaging. METHODS: Ten
      cadaveric hands and ten knees were examined using a dedicated CBCT prototype and
      a clinical multi-detector CT using nominal protocols (80 kVp-108mAs for CBCT; 120
      kVp- 300 mAs for MDCT). Soft tissue and bone visualization tasks were assessed by
      four radiologists using five-point satisfaction (for CBCT and MDCT individually)
      and five-point preference (side-by-side CBCT versus MDCT image quality
      comparison) rating tests. Ratings were analyzed using Kruskal-Wallis and Wilcoxon
      signed-rank tests, and observer agreement was assessed using the Kappa-statistic.
      RESULTS: Knee CBCT images were rated "excellent" or "good" (median scores 5 and
      4) for "bone" and "soft tissue" visualization tasks. Hand CBCT images were rated
      "excellent" or "adequate" (median scores 5 and 3) for "bone" and "soft tissue"
      visualization tasks. Preference tests rated CBCT equivalent or superior to MDCT
      for bone visualization and favoured the MDCT for soft tissue visualization tasks.
      Intraobserver agreement for CBCT satisfaction tests was fair to almost perfect
      (kappa ~ 0.26-0.92), and interobserver agreement was fair to moderate (kappa ~
      0.27-0.54). CONCLUSION: CBCT provided excellent image quality for bone
      visualization and adequate image quality for soft tissue visualization tasks. KEY
      POINTS: * CBCT provided adequate image quality for diagnostic tasks in extremity
      imaging. * CBCT images were "excellent" for "bone" and "good/adequate" for "soft
      tissue" visualization tasks. * CBCT image quality was equivalent/superior to MDCT
      for bone visualization tasks.

PMID- 25599934
TI  - miR-196a expression in human and canine osteosarcomas: a comparative study.
AB  - Osteosarcoma (OS) is the most common primary malignant bone tumour in dogs and
      humans. MicroRNAs are short non-coding RNA molecules involved in post
      transcriptional gene expression. Here, we compared the effects of miR-196a
      deregulation in human and canine OS cells after having observed a more uniform
      distribution and stronger down-expression in the human specimens. Cell response
      to miR-196a transfection was different in human and canine OS. A decreased
      proliferation rate was seen in human MG63 and 143B OS cells, while no appreciable
      changes occurred in canine DAN cells. Transient decrease of motility was highly
      remarkable and longer in MG63, concomitant with decreased levels of annexin1, a
      target of miR-196a promoting cell migration and invasion. In conclusion, the
      effects of miR-196a over-expression on tumour cell response may be strictly
      related to species and cell type. Further studies are needed to define the impact
      of miRNA deregulation on OS development. 

PMID- 25599935
TI  - Evaluation and histological examination of a Campylobacter fetus subsp.
      venerealis small animal infection model.
AB  - Bovine genital campylobacteriosis (BGC), caused by Campylobacter fetus subsp.
      venerealis, is associated with production losses in cattle worldwide. This study
      aimed to develop a reliable BGC guinea pig model to facilitate future studies of
      pathogenicity, abortion mechanisms and vaccine efficacy. Seven groups of five
      pregnant guinea pigs (1 control per group) were inoculated with one of three
      strains via intra-peritoneal (IP) or intra-vaginal routes. Samples were examined
      using culture, PCR and histology. Abortions ranged from 0% to 100% and re
      isolation of causative bacteria from sampled sites varied with strain, dose of
      bacteria and time to abortion. Histology indicated metritis and placentitis,
      suggesting that the bacteria induce inflammation, placental detachment and
      subsequent abortion. Variation of virulence between strains was observed and
      determined by culture and abortion rates. IP administration of C. fetus subsp.
      venerealis to pregnant guinea pigs is a promising small animal model for the
      investigation of BGC abortion. 

PMID- 25599936
TI  - Nasal isolation of Mannheimia haemolytica and Pasteurella multocida as predictors
      of respiratory disease in shipped calves.
AB  - Three hundred ninety five calves were purchased from sale barns and delivered to
      the Willard Sparks Beef Research Center. Nasal swabs were collected to determine
      if presence of Mannheimia haemolytica and Pasteurella multocida in the upper
      respiratory tract (URT) can facilitate diagnosis of bovine respiratory disease
      (BRD). Samples were collected at arrival and at treatment for BRD. Clinically
      healthy control calves were sampled at time of treatment of sick calves. M.
      haemolytica was more commonly isolated from calves at treatment than at time of
      arrival or from control calves. M. haemolytica was more common in calves
      requiring treatment than in those never treated. Need for treatment and number of
      treatments were negatively associated with average daily gain, supporting the
      accuracy of diagnosis. These results suggest that URT sampling, when combined
      with clinical diagnosis, may assist in providing greater diagnostic accuracy,
      improving ability to evaluate risk factors, interventions, and treatments. 

PMID- 25599937
TI  - Latent variable and network models of comorbidity: toward an empirically derived
      nosology.

PMID- 25599938
TI  - Matrix metalloproteinase interactions with collagen and elastin.
AB  - Most abundant in the extracellular matrix are collagens, joined by elastin that
      confers elastic recoil to the lung, aorta, and skin. These fibrils are highly
      resistant to proteolysis but can succumb to a minority of the matrix
      metalloproteinases (MMPs). Considerable inroads to understanding how such MMPs
      move to the susceptible sites in collagen and then unwind the triple helix of
      collagen monomers have been gained. The essential role in unwinding of the
      hemopexin-like domain of interstitial collagenases or the collagen binding domain
      of gelatinases is highlighted. Elastolysis is also facilitated by the collagen
      binding domain in the cases of MMP-2 and MMP-9, and remote exosites of the
      catalytic domain in the case of MMP-12. 

PMID- 25599940
TI  - Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins.
AB  - Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae
      infections (KPC-EI) remains a challenge. Combined therapy has been proposed as
      the best choice, but there are no clear data showing which combination therapy is
      superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for
      treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial
      infections (based on CDC criteria) between October 2009 and June 2013 at three
      tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for
      all infections and the 30-day mortality for patients with bacteraemia. Risk
      factors for mortality were evaluated by comparing clinical variables of survivors
      and nonsurvivors. In this study, 118 patients were included, of whom 78 had
      bacteraemia. Catheter-related bloodstream infections were the most frequent
      (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used
      in 57 patients and combined treatment in 61 patients. The most common therapeutic
      combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all
      infections (n = 118) and for bacteremic infections (n = 78) revealed that renal
      failure at the end of treatment, use of polymyxin and older age were prognostic
      factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and
      combination therapy was not superior to monotherapy.

PMID- 25599939
TI  - Matrix metalloproteinases in liver injury, repair and fibrosis.
AB  - The liver is a large highly vascularized organ with a central function in
      metabolic homeostasis, detoxification, and immunity. Due to its roles, the liver
      is frequently exposed to various insults which can cause cell death and hepatic
      dysfunction. Alternatively, the liver has a remarkable ability to self-repair and
      regenerate after injury. Liver injury and regeneration have both been linked to
      complex extracellular matrix (ECM) related pathways. While normal degradation of
      ECM components is an important feature of tissue repair and remodeling, irregular
      ECM turnover contributes to a variety of liver diseases. Matrix
      metalloproteinases (MMPs) are the main enzymes implicated in ECM degradation.
      MMPs not only remodel the ECM, but also regulate immune responses. In this
      review, we highlight some of the MMP-attributed roles in acute and chronic liver
      injury and emphasize the need for further experimentation to better understand
      their functions during hepatic physiological conditions and disease progression. 

PMID- 25599941
TI  - How well does physician selection of microbiologic tests identify Clostridium
      difficile and other pathogens in paediatric diarrhoea? Insights using multiplex
      PCR-based detection.
AB  - The objective of this study was to compare the aetiologic yield of standard-of
      care microbiologic testing ordered by physicians with that of a multiplex PCR
      platform. Stool specimens obtained from children and young adults with
      gastrointestinal illness were evaluated by standard laboratory methods and a
      developmental version of the FilmArray Gastrointestinal (GI) Diagnostic System
      (FilmArray GI Panel), a rapid multiplex PCR platform that detects 23 bacterial,
      viral and protozoal agents. Results were classified according to the
      microbiologic tests requested by the treating physician. A median of three (range
      1-10) microbiologic tests were performed by the clinical laboratory during 378
      unique diarrhoeal episodes. A potential aetiologic agent was identified in 46% of
      stool specimens by standard laboratory methods and in 65% of specimens tested
      using the FilmArray GI Panel (p < 0.001). For those patients who only had
      Clostridium difficile testing requested, an alternative pathogen was identified
      in 29% of cases with the FilmArray GI Panel. Notably, 11 (12%) cases of norovirus
      were identified among children who only had testing for Clostridium difficile
      ordered. Among those who had C. difficile testing ordered in combination with
      other tests, an additional pathogen was identified in 57% of stool specimens with
      the FilmArray GI Panel. For patients who had no C. difficile testing performed,
      the FilmArray GI Panel identified a pathogen in 63% of cases, including C.
      difficile in 8%. Physician-specified laboratory testing may miss important
      diarrhoeal pathogens. Additionally, standard laboratory testing is likely to
      underestimate co-infections with multiple infectious diarrhoeagenic agents.

PMID- 25599942
TI  - The effects of prone position ventilation in patients with acute respiratory
      distress syndrome. A systematic review and metaanalysis.
AB  - INTRODUCTION: Prone position ventilation has been shown to improve oxygenation
      and ventilatory mechanics in patients with acute respiratory distress syndrome.
      We evaluated whether prone ventilation reduces the risk of mortality in adult
      patients with acute respiratory distress syndrome versus supine ventilation.
      METHODOLOGY: A metaanalysis of randomized controlled trials comparing patients in
      supine versus prone position was performed. A search was conducted of the Pubmed,
      Embase, Cochrane Library, and LILACS databases. Mortality, hospital length of
      stay, days of mechanical ventilation and adverse effects were evaluated. RESULTS:
      Seven randomized controlled trials (2,119 patients) were included in the
      analysis. The prone position showed a nonsignificant tendency to reduce mortality
      (OR: 0.76; 95%CI: 0.54 to 1.06; P=.11, I(2) 63%). When stratified by subgroups, a
      significant decrease was seen in the risk of mortality in patients ventilated
      with low tidal volume (OR: 0.58; 95%CI: 0.38 to 0.87; P=.009, I(2) 33%),
      prolonged pronation (OR: 0.6; 95%CI: 0.43 to 0.83; p=.002, I(2) 27%), start
      within the first 48hours of disease evolution (OR 0.49; 95%CI 0.35 to 0.68;
      P=.0001, I(2) 0%) and severe hypoxemia (OR: 0.51: 95%CI: 0.36 to 1.25; P=.0001,
      I(2) 0%). Adverse effects associated with pronation were the development of
      pressure ulcers and endotracheal tube obstruction. CONCLUSIONS: Prone position
      ventilation is a safe strategy and reduces mortality in patients with severely
      impaired oxygenation. It should be started early, for prolonged periods, and
      should be associated to a protective ventilation strategy.

PMID- 25599944
TI  - Intravenous ketamine bolus: not so fast!

PMID- 25599943
TI  - The Ethics of Using the Recently Deceased to Instruct Residents in
      Cricothyrotomy.
AB  - Cricothyrotomy is a rare but crucial procedure in the armamentarium of the
      emergency physician. The infrequency with which it is performed has led to a
      reliance on models, simulators, and animals in resident education, but each of
      these methods has unique drawbacks. Using recently deceased patients as teaching
      tools has a long history in medicine, though controversy surrounds whether, how,
      and from whom consent ought to be obtained. Recent studies have shown that
      families expect to be asked for permission and often will grant it, even for
      invasive procedures such as cricothyrotomy. Obtaining consent maintains the
      integrity of the relationship among the physician, the deceased, the family, and
      the community and need not prohibit performing procedures on the newly dead for
      the purpose of resident education. Thus, a balanced approach to resident
      instruction that incorporates the use of the deceased in addition to other
      methods of instruction seems both prudent and feasible. 

PMID- 25599946
TI  - Biology, metaphysics, and brain death criteria.

PMID- 25599945
TI  - Tissue perfusion and oxygenation to monitor fluid responsiveness in critically
      ill, septic patients after initial resuscitation: a prospective observational
      study.
AB  - Fluid therapy after initial resuscitation in critically ill, septic patients may
      lead to harmful overloading and should therefore be guided by indicators of an
      increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to
      investigate whether tissue perfusion and oxygenation are able to monitor fluid
      responsiveness, even after initial resuscitation. Thirty-five critically ill,
      septic patients underwent infusion of 250 mL of colloids, after initial fluid
      resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual
      microcirculatory perfusion (SDF: sidestream dark field imaging) and skin
      perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy)
      were measured. Fluid responsiveness was defined by a >=5 or 10% increase in SV
      upon fluids. In responders to fluids, SDF-derived microcirculatory and skin
      perfusion and oxygenation increased, but only the increase in cardiac output,
      mean arterial and pulse pressure, microvascular flow index and relative Hb
      concentration and oxygen saturation were able to monitor a SV increase. Our proof
      of principle study demonstrates that non-invasively assessed tissue perfusion and
      oxygenation is not inferior to invasive hemodynamic measurements in monitoring
      fluid responsiveness. However skin reflectance spectroscopy may be more helpful
      than sublingual SDF.

PMID- 25599947
TI  - The use of tracheostomy speaking valves in mechanically ventilated patients
      results in improved communication and does not prolong ventilation time in
      cardiothoracic intensive care unit patients.
AB  - PURPOSE: The aim of this study was to assess the effect of the introduction of in
      line tracheostomy speaking valves (SVs) on duration of mechanical ventilation and
      time to verbal communication in patients requiring tracheostomy for prolonged
      mechanical ventilation in a predominantly cardiothoracic intensive care unit
      (ICU). MATERIALS AND METHODS: We performed a retrospective preobservational
      postobservational study using data from the ICU clinical information system and
      medical record. Extracted data included demographics, diagnoses and disease
      severity, mechanical ventilation requirements, and details on verbal
      communication and oral intake. RESULTS: Data were collected on 129 patients. Mean
      age was 59 +/- 16 years, with 75% male. Demographics, case mix, and median time
      from intubation to tracheostomy (6 days preimplementation-postimplementation)
      were unchanged between timepoints. A significant decrease in time from
      tracheostomy to establishing verbal communication was observed (18 days
      preimplementation and 9 days postimplementation, P <.05). There was no difference
      in length of mechanical ventilation (20 days preimplementation-post) or time to
      decannulation (14 days preimplementation-postimplementation). No adverse events
      were documented in relation to the introduction of in-line SVs. CONCLUSIONS: In
      line SVs were successfully implemented in mechanically ventilated tracheostomized
      patient population. This resulted in earlier verbal communication, no detrimental
      effect on ventilator weaning times, and no change in decannulation times.
      PURPOSE: The purpose of the study was to compare tracheostomy outcomes in
      mechanically ventilated patients in a cardiothoracic ICU preintroduction and
      postintroduction of in-line SVs. It was hypothesized that in-line SVs would
      improve communication and swallowing specific outcomes with no increase in
      average time to decannulation or the number of adverse events.

PMID- 25599948
TI  - Design and synthesis of pyrazole-oxindole conjugates targeting tubulin
      polymerization as new anticancer agents.
AB  - A series of twenty one compounds with pyrazole and oxindole conjugates were
      synthesized by Knoevenagel condensation and investigated for their
      antiproliferative activity on different human cancer cell lines. The conjugates
      are comprised of a four ring scaffold; the structural isomers 12b and 12c possess
      chloro-substitution in the D ring. Among the congeners 12b, 12c, and 12d
      manifested significant cytotoxicity and inhibited tubulin assembly. Treatments
      with 12b, 12c and 12d resulted in accumulation of cells in G2/M phase, disruption
      of microtubule network, and increase in cyclin B1 protein. Zebrafish screening
      revealed that 12b, and 12d caused developmental defects. Docking analysis
      demonstrated that the congeners occupy the colchicine binding pocket of tubulin. 

PMID- 25599949
TI  - Medicinal uses, phytochemistry and pharmacology of family Sterculiaceae: a
      review.
AB  - The family Sterculiaceae is one of the most important families among flowering
      plants. Many of its members demonstrate medicinal properties and have been used
      for the treatment of various ailments and wounds. A wide range of compounds
      including alkaloids, phenyl propanoids, flavonoids, terpenoids and other types of
      compounds including hydrocarbons, sugars, quinones, phenolic acids, lactones,
      lignans, amine and amides have been isolated from several species in this family.
      Few studies have reported that some extracts and single compounds isolated from
      this family exhibited several biological activities, such as antimicrobial, anti
      inflammatory, antioxidant and cytotoxic activities. The present review is an
      effort to provide information about the traditional uses, phytochemistry and
      pharmacology of species from family Sterculiaceae, and to uncover the gaps and
      potentials requiring further research opportunities regarding the chemistry and
      pharmacy of this family. 

PMID- 25599950
TI  - Probes for narcotic receptor mediated phenomena 49. N-substituted rac-cis-4a
      arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.
AB  - Racemic N-substituted -1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols
      containing cis-4a-aralkyl groups were explored as probes for opioid receptors.
      Specifically cis-4a-phenylpropyl, -phenylbutyl, and-phenylpentyl groups coupled
      with widely varied substituents on the nitrogen atom were synthesized and their
      pharmacological profiles at opioid receptors examined. The study yielded
      compounds with good affinity and moderate to potent antagonist activity at the MU
      and delta-opioid receptors, and agonist activity at the kappa-opioid receptor.
      An N-allyl substituent in the C4a phenylpropyl series induced 6-fold higher
      affinity at delta-than MU-receptors, while an N-CPM substituent in the C4a
      (CH2)3Ph series led to a compound with high delta-affinity and potent delta
      antagonist activity. 

PMID- 25599951
TI  - Design, synthesis and biological evaluation of novel 7-alkylamino substituted
      benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors.
AB  - A novel series of benzo[a]phenazin derivatives bearing alkylamino side chains
      were designed, synthesized and evaluated for their topoisomerases inhibitory
      activity as well as cytotoxicity against four human cancer cell lines (HL-60, K
      562, HeLa, and A549). These compounds were found to be dual inhibitors of
      topoisomerase (Topo) I and Topo II, and exhibited excellent antiproliferative
      activity, in particular against HL-60 cells with submicromolar IC50 values.
      Further mechanistic studies showed that this class of compounds acted as Topo I
      poisons by stabilizing the Topo I-DNA cleavage complexes and Topo II catalytic
      inhibitors by inhibiting the ATPase activity of hTopo II. Molecular docking
      studies revealed the binding modes of these compounds for Topo I and Topo II. 

PMID- 25599952
TI  - Synthesis, radiolabeling and evaluation of novel 4-oxo-quinoline derivatives as
      PET tracers for imaging cannabinoid type 2 receptor.
AB  - Our goal is to develop a highly specific and selective PET brain tracer for
      imaging CB2 expression in patients with neuroinflammatory diseases. Based on our
      previous findings on a carbon-11 labeled 4-oxo-quinoline structure, designated
      KD2, further structural optimizations were performed, which led to the discovery
      of N-(1-adamantyl)-1-(2-ethoxyethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3
      carboxamide (RS-016). Compared to KD2, RS-016 exhibits a higher binding affinity
      towards CB2 (Ki = 0.7 nM) with a selectivity over CB1 of >10,000 and lower
      lipophilicity (logD7.4 = 2.78). [(11)C]RS-016 was obtained in >=99% radiochemical
      purity and up to 850GBq/MUmol specific radioactivity at the end of synthesis. In
      vitro autoradiography on rodent spleen tissue showed high specific binding to
      CB2. [(11)C]RS-016 was stable in vitro in rodent and human plasma over 40 min,
      whereas 47% intact compound was found in vivo in rat blood plasma 20 min post
      injection (p.i.). High specific binding to CB2 was observed in murine spleen
      tissues and postmortem ALS patient spinal cord tissues in vitro autoradiography,
      ex vivo biodistribution data confirmed the high and specific uptake of [(11)C]RS
      016 in spleen region in rats. In vivo specificity of [(11)C]RS-016 could also be
      shown in brain by PET imaging using a murine neuroinflammation model, which has
      higher CB2 receptor expression level in the brain induced by lipopolysaccharide
      (LPS) application. 

PMID- 25599953
TI  - Inhalable dry powder formulations of siRNA and pH-responsive peptides with
      antiviral activity against H1N1 influenza virus.
AB  - Pulmonary delivery of siRNA has considerable therapeutic potential for treating
      viral respiratory infectious diseases including influenza. By introducing siRNA
      that targets the conserved region of viral genes encoding nucleocapsid protein
      (NP), viral mRNAs can be degraded and viral replication can be inhibited in
      mammalian cells. To enable siRNA to be used as an antiviral agent, the nucleic
      acid delivery barrier must be overcome. Effective local delivery of siRNA to lung
      tissues is required to reduce the therapeutic dose and minimize systemic adverse
      effects. To develop a formulation suited for clinical application, complexes of
      pH-responsive peptides, containing either histidine or 2,3-diaminopropionic acid
      (Dap), and siRNA were prepared into dry powders by spray drying with mannitol,
      which was used as a bulking agent. The spray-dried (SD) powders were
      characterized and found to be suitable for inhalation with good stability,
      preserving the integrity of the siRNA as well as the biological and antiviral
      activities. The formulations mediated highly effective in vitro delivery of
      antiviral siRNA into mammalian lung epithelial cells, leading to significant
      inhibition of viral replication when the transfected cells were subsequently
      challenged with H1N1 influenza virus. SD siRNA powders containing pH-responsive
      peptides are a promising inhalable formulation to deliver antiviral siRNA against
      influenza and are readily adapted for the treatment of other respiratory
      diseases. 

PMID- 25599954
TI  - The effect of a triple therapy on maternal anti-Ro/SS-A levels associated to
      fetal cardiac manifestations.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the combination of steroids,
      plasmapheresis and intravenous immunoglobulins (IVIG) on maternal anti Ro/SS-A
      antibody levels in cases of fetal cardiac involvement. MATERIAL AND METHODS: A
      series of three cases of positive anti-Ro/SS-A mothers with fetuses showing mild
      cardiac involvement were treated with a triple therapy composed of steroids,
      plasmapheresis and IVIG. Maternal antibody levels were measured several times
      before and after the application of each cycle of therapy. The effect of the
      treatment on fetal cardiac manifestations was also evaluated. RESULTS: Maternal
      anti-Ro/SS-A levels significantly decreased after each cycle of either
      plasmapheresis or IVIG therapy. The most significant decrease occurred after the
      first cycle. The natural evolution of the disease was stopped by this therapy in
      two of these cases, signs of cardiac inflammation decrease and none of the
      newborns needed neonatal pacemaker. CONCLUSIONS: A triple therapy combining
      plasmapheresis, IVIG and glucocorticoids may stop the natural evolution of the
      fetal cardiac affectation in positive anti-Ro/SS-A antibody patients. Further
      studies are needed in order to validate clinical applications of this treatment
      approach.

PMID- 25599955
TI  - Increased level of H-ferritin and its imbalance with L-ferritin, in bone marrow
      and liver of patients with adult onset Still's disease, developing macrophage
      activation syndrome, correlate with the severity of the disease.
AB  - In this paper, we aimed to evaluate the levels of ferritin enriched in H subunits
      (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells
      expressing these 2 molecules, in the bone marrow (BM) and liver biopsies obtained
      from adult onset Still's disease (AOSD) patients who developed macrophage
      activation syndrome (MAS), and correlating these data with the severity of the
      disease. Twenty-one patients with MAS-associated AOSD underwent BM biopsy and
      among them, 9 patients with hepatomegaly and elevated liver enzymes underwent
      liver biopsy. All the samples were stained by both immunohistochemistry and
      immunofluorescence. A statistical analysis was performed to estimate the possible
      correlation among both H-ferritin and L-ferritin tissue expression and the
      clinical picture of the disease. Furthermore, the same analysis was performed to
      evaluate the possible correlation among the number of CD68/H-ferritin or CD68/L
      ferritin positive cells and the clinical picture. Both immunohistochemical and
      immunofluorescence analysis demonstrated an increased tissue H-ferritin
      expression, in the BM and liver samples of our patients. This increased
      expression correlated with the severity of the disease. An inflammatory
      infiltrate, enriched in CD68 macrophages, expressing H-ferritin was observed in
      both the BM and the liver samples of our patients. Furthermore, we observed, that
      this increased number of CD68/H-ferritin positive cells significantly correlated
      with the severity of clinical picture and this specific BM infiltrate correlated
      with the mortality rate, reported in our cohort. Our data showed an imbalance
      between the levels of H- and L-ferritin in different organs of patients with MAS
      associated AOSD and the evidence of a strong infiltrate of CD68/H-ferritin
      positive cells in the same organs. Furthermore, a strong correlation among both
      the tissue H-ferritin and the CD68/H-ferritin positive cells and the clinical
      picture was observed.

PMID- 25599956
TI  - The impact of illness perceptions and disease severity on quality of life in
      congenital heart disease.
AB  - BACKGROUND: Despite an increasing prevalence of adults living with a CHD, little
      is known about the psychosocial impact of CHD. We sought to investigate the
      relative impact of disease severity and patients' perceptions about their
      condition on depression, anxiety, and quality of life over a period of a year.
      METHODS: A total of 110 patients aged over 16 years completed an initial
      questionnaire containing measures for anxiety, depression, quality of life, and
      illness perceptions when they attended the Adult Congenital Heart Disease Clinic.
      Cardiologists rated the patients' disease severity and illness course. A year
      later, patients were invited to complete the same measures. Regression analyses
      were performed to determine the relative impact of illness perceptions and
      disease severity on psychological outcomes a year later. RESULTS: At baseline,
      23% of the study population had depressive symptoms and 30% had elevated trait
      anxiety. After controlling for associations with disease-related variables,
      illness perceptions explained 28% of the variance in depression, 40% anxiety, and
      27% overall quality of life at baseline. Baseline illness perceptions bivariately
      predicted quality of life, cardiac anxiety, and depression 1 year later, and
      regression analyses controlling for other factors showed that they were
      significant predictors of outcomes 1 year later. CONCLUSION: Symptoms of
      depression and anxiety are common among adults with CHD. Patients' illness
      perceptions are related to psychological outcomes, especially cross-sectionally.
      Future research could investigate whether an intervention to discuss patients'
      perceptions about their CHD can improve mental health and quality of life.

PMID- 25599957
TI  - Unintentional parathyroidectomy and postoperative hypocalcaemia. Conventional
      thyroidectomy versus miniinvasive thyroidectomy.
AB  - BACKGROUND: Hypocalcemia and unintentional parathyroidectomy would be associated
      as cause of post-thyroidectomy hypocalcemia. MATERIALS AND METHODS: We analysed
      the cases treated with total thyroidectomy by two experienced endocrine surgeons
      from January 2010 to December 2011 at the Unit of General Surgery and Organ
      Transplantation of the University Hospital of Parma. These cases were divided in
      two groups: "Group A" included patients for whom a histological report was made
      that was negative for a parathyroid avulsion, and "Group B" included patients for
      whom an inadvertent avulsion of the intracapsular parathyroid glands had
      occurred. RESULTS: In total, 538 patients were treated with a total thyroidectomy
      from January 2010 to December 2011. In 26 cases, the histological report
      highlighted the presence of an intracapsular parathyroid gland. The values of pre
      operative calcaemia in group A and group B were 9.204 +/- 0.2703 mg/dl versus
      9.283 +/- 0.401 mg/dl, respectively (p=0.32). The values of post-operative
      calcaemia were 8.039 +/- 0.596 mg/dl for group A versus 7.569 +/- 0.618 mg/dl for
      group B (p=0.0002) In Group A, 91/512 patients were treated with the minimally
      invasive video-assisted thyroidectomy (MIVAT) technique (17,7%), while 1/26
      patients in group B was treated with a MIVAT (3,8%). DISCUSSION: Unintentional
      parathyroidectomies can occur with experienced surgeons, but this complication is
      not related to a substantial difference in the incidence of hypocalcemia. MIVAT
      can helps the endocrine surgeon in the detection of the parathyroids glands, but
      when the parathyroid is intracapsular, is difficult to preserve it, during
      surgical dissection.

PMID- 25599958
TI  - The history of colorectal cancer screening: a personal perspective.
AB  - The present explosive interest in screening for colorectal cancer (CRC), one of
      the most prevalent and preventable cancers, had its beginnings at a hospital in
      London and an Internist's office in Ohio. Demonstrated there were the concepts
      that CRC did not occur de-novo but arose from a premalignant polyp, that
      detection of the resultant cancer at an earlier stage was associated with better
      survival and that cancer could be detected at an early presymptomatic stage by
      screening. Many years later, the introduction of colonoscopy and colonoscopic
      polypectomy provided the opportunity for randomized trials to prove that these
      concepts were true. The sequence of rigorous science followed by guidelines
      consensus and then multilevel national efforts of screening implementation has
      resulted in a decline in the CRC incidence and mortality worldwide, most
      significantly in the USA. Campaigns have been initiated to maximize population
      screening and further investigate its optimal approach. Some historical details
      of this success story and many of the key participants are presented in this
      paper. 

PMID- 25599959
TI  - Regional Bias of Intratumoral Genetic Heterogeneity of Apoptosis-Related Genes
      BAX, APAF1, and FLASH in Colon Cancers with High Microsatellite Instability.
AB  - BACKGROUND: Apoptosis inactivation and intratumoral heterogeneity (ITH) are
      common features of cancers, including colorectal cancer (CRC). Inactivation of
      apoptosis prolongs cancer cell survival, and ITH may contribute to CRC
      progression. AIM: To examine the presence and extent of mutational ITH in the pro
      apoptotic genes APAF1, BAX, and FLASH and the association of mutational ITH with
      pathologic parameters of CRC. METHODS: The ITH of mutations in the mononucleotide
      repeats of APAF1, BAX and FLASH in different tumors were analyzed in 16 cases of
      CRC with high microsatellite instability (MSI-H) and 41 cases of CRC with stable
      MSI/low MSI (MSS/MSI-L) by single-strand conformation polymorphism and DNA
      sequencing analyses. RESULTS: Frameshift mutations of APAF1, BAX, and FLASH were
      identified in 19, 31, and 6 % of CRC with MSI-H, respectively, but also in cases
      of CRC with MSS/MSI-L. All but one CRC with a mutation (8/9) harbored regional
      ITH of the APAF1, BAX and FLASH frameshift mutations. ITH, however, was not
      associated with histopathologic features of CRC with MSI-H, suggesting that ITH
      might not be related to development of the MSI-H phenotype itself, but rather to
      disease progression. CONCLUSIONS: Our results indicate that the APAF1, BAX, and
      FLASH genes not only harbor frameshift mutations but also demonstrate mutational
      ITH, which together might play a role in the tumorigenesis of CRC with MSI-H by
      affecting the apoptosis of cancer cells. Our data also suggest that multiregional
      mutation analysis is needed for a better evaluation of the mutation status in
      CRC.

PMID- 25599961
TI  - Helicobacter pylori Infection Status Correlates with Serum Parameter Levels
      Responding to Multi-organ Functions.
AB  - BACKGROUND: Epidemiological studies have demonstrated the relationship between
      Helicobacter pylori infection and gastric and extra-gastric diseases. Therefore,
      H. pylori infection might be a "systemic" disease. AIM: To investigate the
      relationship between H. pylori infection status and serum parameter levels
      responding to multi-organ functions. METHODS: A total of 2,044 subjects were
      selected, including 1,249 males and 795 females with ages ranging from 16 to 86
      years. Relevant parameters including blood lipids, complete blood count, tumor
      markers, indexes of stomach, kidney, liver, thyroid, and immune system function,
      H.pylori IgG antibody levels, and (14)C-UBT were collected. RESULTS: Serum
      pepsinogen (PG)I, PGII, and gastrin (G)17 levels were decreased in chronic long
      term, past, and acute short-term infection patients compared with uninfected
      controls. However, the serum PGI/II ratio increased gradually. Serum white blood
      cell levels gradually decreased in past, chronic long-term, and acute short-term
      infection patients compared with uninfected controls. The same trend was also
      observed for CD4(+) T cell levels. In addition, LDL levels were higher in chronic
      long-term infection, HDL levels were lower in past infection, and ALP and CEA
      levels were higher in acute short-term infection compared with the uninfected
      group. CONCLUSIONS: Helicobacter pylori infection correlated with increased PGI,
      PGII, G17, WBC, and CD4(+) T cell levels, and decreased PGI/II ratio. In chronic
      long-term or past infection, H. pylori infection was associated with higher LDL
      or lower HDL levels. In acute short-term infection, H. pylori infection
      correlated with higher ALP and CEA levels. H. pylori infection correlated with
      serum parameter levels responding to multi-organ functions.

PMID- 25599960
TI  - Prevalence of esophageal eosinophilia and eosinophilic esophagitis in adults: a
      population-based endoscopic study in Shanghai, China.
AB  - BACKGROUND AND AIM: Population-based endoscopic studies of esophageal
      eosinophilia and eosinophilic esophagitis are limited in the world. This study
      was aiming to describe features of esophageal eosinophilia and eosinophilic
      esophagitis in a representative sample of the adult in Shanghai, China. METHODS:
      As part of a large epidemiological study, 3,600 individuals (aged 18-80 years)
      were randomly selected in Shanghai, China. They were asked to undergo endoscopy
      and have at least four esophageal biopsies taken from 0.5 cm above the Z-line and
      any abnormal areas. Any eosinophil infiltration of the epithelium was defined as
      esophageal eosinophilia. Eosinophilic esophagitis was defined as >=15
      eosinophils/high-power field in esophageal biopsies. RESULTS: A total of 1,030
      individuals accepted to have endoscopy and 1,021 individuals with biopsy results
      were suitable for analysis. Esophageal eosinophilia was present in 67 subjects
      (6.6 %). Eosinophilic esophagitis was present in four cases (0.4 %). No
      significant association was found between the presence of esophageal eosinophilia
      and reflux esophagitis, Barrett's esophagus, symptom-defined gastroesophageal
      reflux disease or H. pylori infection. Most individuals with esophageal
      eosinophilia (80.6 %) did not have any of the upper gastrointestinal symptoms.
      CONCLUSIONS: Esophageal eosinophilia was present in nearly 6.6 % of the general
      adult population of China; 0.4 % had eosinophilic esophagitis. Most of
      individuals with esophageal eosinophilia were asymptomatic.

PMID- 25599963
TI  - Excessive degradation of adenine nucleotides by up-regulated AMP deaminase
      underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart.
AB  - Type 2 diabetes mellitus (T2DM) is often complicated with diastolic heart
      failure, which decompensates under increased afterload. Focusing on cardiac
      metabolomes, we examined mechanisms by which T2DM augments ventricular diastolic
      stiffness in response to pressure overloading. Pressure-volume relationships
      (PVRs) and myocardial metabolomes were determined at baseline and during
      elevation of aortic pressure by phenylephrine infusion in a model of T2DM, OLETF,
      and its non-diabetic control, LETO. Pressure overloading augmented diastolic
      stiffness without change in systolic reserve in OLETF as indicated by a left
      upward shift of end-diastolic PVR. In contrast, PVRs under cardioplegic arrest in
      buffer-perfused isolated hearts were similar in OLETF and LETO, indicating that
      extracellular matrix or titin remodeling does not contribute to the afterload
      induced increase in stiffness of the beating ventricle of OLETF. Metabolome
      analyses revealed impaired glycolysis and facilitation of the pentose phosphate
      pathway in OLETF. Pressure overloading significantly reduced ATP and total
      adenine nucleotides by 34% and 40%, respectively, in OLETF but not in LETO, while
      NADH-to-NAD(+) ratios were similar in the two groups. The decline in ATP by
      pressure overloading in OLETF was associated with increased inosine 5
      monophosphate and decreased adenosine levels, being consistent with the 2.5-times
      higher activity of cardiac AMP deaminase in OLETF. Tissue ATP level was
      negatively correlated with tau of LV pressure and LVEDP. These results suggest
      that ATP depletion due to excessive degradation of adenine nucleotides by up
      regulated AMP deaminase underlies ventricular stiffening during acute pressure
      overloading in T2DM hearts.

PMID- 25599962
TI  - Risk factors for relapse to problem drinking among current and former US military
      personnel: a prospective study of the Millennium Cohort.
AB  - BACKGROUND: Military service members may be prone to relapse to problem drinking
      after remission, given a culture of alcohol use as a coping mechanism for
      stressful or traumatic events associated with military duties or exposures.
      However, the prevalence and correlates of relapse are unknown. We sought to
      identify socio-demographic, military, behavioral, and health characteristics
      associated with relapse among current and former military members with remittent
      problem drinking. METHODS: Participants in the longitudinal Millennium Cohort
      Study who reported problem drinking at baseline (2001-2003) and were remittent at
      first follow-up (2004-2006) were included (n=6909). Logistic regression models
      identified demographic, military service, behavioral, and health characteristics
      that predicted relapse (report of >=1 past-year alcohol-related problem on the
      validated Patient Health Questionnaire) at the second follow-up (2007-2008).
      RESULTS: Sixteen percent of those with remittent problem drinking relapsed.
      Reserve/National Guard members compared with active-duty members (odds ratio
      [OR]=1.71, 95% confidence interval [CI]: 1.45-2.01), members separated from the
      military during follow-up (OR=1.46, 95% CI: 1.16-1.83), and deployers who
      reported combat exposure (OR=1.32, 95% CI: 1.07-1.62, relative to non-deployers)
      were significantly more likely to relapse. Those with multiple deployments were
      significantly less likely to relapse (OR=0.73, 95% CI: 0.58-0.92). Behavioral
      factors and mental health conditions also predicted relapse. CONCLUSION: Relapse
      was common and associated with military and non-military factors. Targeted
      intervention to prevent relapse may be indicated for military personnel in
      particular subgroups, such as Reservists, veterans, and those who deploy with
      combat exposure.

PMID- 25599964
TI  - Pulmonary artery pseudoaneurysm after radiofrequency ablation: report of two
      cases.
AB  - We report two cases of pulmonary arterial pseudoaneurysms (PAs) following
      percutaneous radiofrequency ablation (PRFA). The first patient was a 74-year-old
      Caucasian man who was treated for a secondary location of an advanced melanoma. A
      computed tomography scan at 72 h after the procedure, performed for basithoracic
      pain, hyperthermia and haemoptysis, revealed a 17-mm PA within the ablative zone.
      A lobectomy was performed. The second patient was an 80-year-old white man
      followed up for a right apical lung adenocarcinoma. Massive haemoptysis occurred
      24 h after PRFA; emergent contrast-enhanced CT and pulmonary arteriography
      revealed a pulmonary artery PA (20 mm diameter), which was embolised with coils.
      The initial clinical course was satisfactory; however, 15 days after the
      procedure, the patient unfortunately presented a new massive haemoptysis and died
      a few hours later. The long ablation duration and the multiple repositioning of
      the electrodes might have been risk factors for this rare and potentially lethal
      complication.

PMID- 25599967
TI  - Three men infected with hepatitis C through contaminated blood start legal
      proceedings against UK government.

PMID- 25599966
TI  - The relationship between fasting plasma citrulline concentration and small
      intestinal function in the critically ill.
AB  - INTRODUCTION: In this study, we aimed to evaluate whether fasting plasma
      citrulline concentration predicts subsequent glucose absorption in critically ill
      patients. METHODS: In a prospective observational study involving 15 healthy and
      20 critically ill subjects, fasting plasma citrulline concentrations were assayed
      in blood samples immediately prior to the administration of a liquid test meal (1
      kcal/ml; containing 3 g of 3-O-methylglucose (3-OMG)) that was infused directly
      into the small intestine. Serum 3-OMG concentrations were measured over the
      following 4 hours, with the area under the 3-OMG concentration curve (AUC)
      calculated as an index of glucose absorption. RESULTS: The groups were well
      matched in terms of age, sex and body mass index (BMI) (healthy subjects versus
      patients, mean (range) values: age, 47 (18 to 88) versus 49 (21 to 77) years; sex
      ratio, 60% versus 80% male; BMI, 25.2 (18.8 to 30.0) versus 25.5 (19.4 to 32.2)
      kg/m(2)). Compared to the healthy subjects, patients who were critically ill had
      reduced fasting citrulline concentration (26.5 (13.9 to 43.0) versus 15.2 (5.7 to
      28.6) MUmol/L; P < 0.01) and glucose absorption (3-OMG AUC, 79.7 (28.6 to 117.8)
      versus 61.0 (4.5 to 97.1) mmol/L/240 min; P = 0.05). There was no relationship
      between fasting citrulline concentration and subsequent glucose absorption (r =
      0.28; P = 0.12). CONCLUSIONS: Whereas both plasma citrulline concentrations and
      glucose absorption were reduced in critical illness, fasting plasma citrulline
      concentrations were not predictive of subsequent glucose absorption. These data
      suggest that fasting citrulline concentration does not appear to be a marker of
      small intestinal absorptive function in patients who are critically ill.

PMID- 25599969
TI  - A continuous-flow microfluidic syringe filter for size-based cell sorting.
AB  - This communication presents a microfluidic method for size-based cell sorting,
      which provides a simple and robust approach for cell cycle synchronization by
      manual and stand-alone operation. 

PMID- 25599968
TI  - Buprenorphine Transdermal System Improves Sleep Quality and Reduces Sleep
      Disturbance in Patients with Moderate-to-Severe Chronic Low Back Pain: Results
      from Two Randomized Controlled Trials.
AB  - OBJECTIVE: To evaluate the impact of buprenorphine (Butrans(r)) transdermal
      System (BTDS) treatment on sleep outcomes for patients with moderate-to-severe
      chronic low back pain (CLBP). METHODS: Two enriched-enrollment, randomized
      withdrawal, double-blind, controlled trials examined BTDS treatment for patients
      with moderate-to-severe CLBP. Trial I evaluated BTDS 10 and 20 mcg/hour against a
      placebo control among opioid-naive patients. Trial II compared BTDS 20 mcg/hour
      against a lower-dose control (BTDS 5 mcg/hour) among opioid-experienced patients.
      The patient-reported Medical Outcomes Study Sleep Scale (MOS-SS) assessed overall
      sleep quality (Sleep Problems Index [SPI]), Disturbance, and other sleep
      outcomes. In each trial, MOS-SS scores were compared between target treatment and
      control arms during the 12-week double-blind phase. Correspondence of changes in
      sleep outcomes and pain severity and the degree to which pain reduction mediates
      treatment impact on sleep outcomes were examined. RESULTS: Medical Outcomes Study
      Sleep Scale scores were collected from 541 (Trial I) and 441 (Trial II) patients
      prior to randomization and from 369 (Trial I) and 274 (Trial II) patients at week
      12. Patients receiving target treatment showed statistically significantly more
      improvement in SPI and Disturbance scores at 12 weeks than their respective
      controls (Ps < 0.05). Improvements in SPI and Disturbance for target treatment
      arms were statistically larger those of the controls by week 4 of the double
      blind phase. The clinical significance of these differences was not determined.
      Pain reduction predicted improvements in sleep outcomes. CONCLUSION:
      Buprenorphine Transdermal System improved sleep quality and disturbance for
      opioid-naive and opioid-experienced patients with moderate-to-severe CLBP.
      Benefits of BTDS for these sleep outcomes emerged within 4 weeks and were
      maintained over the entire 12-week treatment period.

PMID- 25599970
TI  - The crosstalk between the kidney and the central nervous system: the role of
      renal nerves in blood pressure regulation.
AB  - NEW FINDINGS: What is the topic of this review? This review describes the role of
      renal nerves as the key carrier of signals from the kidneys to the CNS and vice
      versa; the brain and kidneys communicate through this carrier to maintain
      homeostasis in the body. What advances does it highlight? Whether renal or
      autonomic dysfunction is the predominant contributor to systemic hypertension is
      still debated. In this review, we focus on the role of the renal nerves in a
      model of renovascular hypertension. The sympathetic nervous system influences the
      renal regulation of arterial pressure and body fluid composition. Anatomical and
      physiological evidence has shown that sympathetic nerves mediate changes in
      urinary sodium and water excretion by regulating the renal tubular water and
      sodium reabsorption throughout the nephron, changes in the renal blood flow and
      the glomerular filtration rate by regulating the constriction of renal
      vasculature, and changes in the activity of the renin-angiotensin system by
      regulating the renin release from juxtaglomerular cells. Additionally, renal
      sensory afferent fibres project to the autonomic central nuclei that regulate
      blood pressure. Hence, renal nerves play a key role in the crosstalk between the
      kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased
      sympathetic nerve activity to the kidney and the renal afferent nerve activity to
      the CNS may contribute to the outcome of diseases, such as hypertension.

PMID- 25599971
TI  - Why have early investigational therapies of obsessive-compulsive disorder failed
      to materialise?
AB  - The mid-1980s brought about a revolution in the way in which clinicians
      approached the treatment of obsessive-compulsive disorder (OCD)
      pharmacologically. Indeed, clinicians adopted the use of selective serotonin (5
      HT) re-uptake inhibitors, as treatment options, when it was demonstrated that OCD
      patients responded specifically to drugs enhancing 5-HT functioning in
      approximately 60% of all cases. Evidence to suggest a role for serotonergic
      compounds in OCD was further elucidated by increasing evidence in the following
      years. Since then, a number of different compounds that more or less directly
      modulate the 5-HT system have been proposed, although other therapeutic targets
      have also been considered. Unfortunately, despite our advancement in the
      understanding of this disorder, several of the treatment proposals never reached
      the clinic, staying at mere suggestion or not receiving sufficient development.
      The aim of this paper is to reflect and comment on the possible reasons that
      might have led to neglect or discarding these drugs that might have been
      effective in treating OCD. 

PMID- 25599973
TI  - Synergistic interplay of a non-heme iron catalyst and amino acid coligands in H2
      O2 activation for asymmetric epoxidation of alpha-alkyl-substituted styrenes.
AB  - Highly enantioselective epoxidation of alpha-substituted styrenes with aqueous H2
      O2 is described by using a chiral iron complex as the catalyst and N-protected
      amino acids (AAs) as coligands. The amino acids synergistically cooperate with
      the iron center in promoting an efficient activation of H2 O2 to catalyze
      epoxidation of this challenging class of substrates with good yields and
      stereoselectivities (up to 97%ee) in short reaction times.

PMID- 25599972
TI  - Neural Correlates of Set-Shifting in Children With Autism.
AB  - Autism spectrum disorder (ASD) is often associated with high levels of inflexible
      thinking and rigid behavior. The neural correlates of these behaviors have been
      investigated in adults and older adolescents, but not children. Prior studies
      utilized set-shifting tasks that engaged multiple levels of shifting, and
      depended on learning abstract rules and establishing a strong prepotent bias.
      These additional demands complicate simple interpretations of the results. We
      used functional magnetic resonance imaging (fMRI) to investigate the neural
      correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically
      developing, matched, control children. Participants completed a set-shifting task
      that minimized nonshifting task demands through the use of concrete instructions
      that provide spatial mapping of stimuli-responses. The shift/stay sets were given
      an equal number of trials to limit the prepotent bias. Both groups showed an
      equivalent "switch cost," responding less accurately and slower to Switch stimuli
      than Stay stimuli, although the ASD group was less accurate overall. Both groups
      showed activation in prefrontal, striatal, parietal, and cerebellum regions known
      to govern effective set-shifts. Compared to controls, children with ASD
      demonstrated decreased activation of the right middle temporal gyrus across all
      trials, but increased activation in the mid-dorsal cingulate cortex/superior
      frontal gyrus, left middle frontal, and right inferior frontal gyri during the
      Switch vs. Stay contrast. The successful behavioral switching performance of
      children with ASD comes at the cost of requiring greater engagement of frontal
      regions, suggesting less efficiency at this lowest level of shifting.

PMID- 25599975
TI  - Design, Synthesis, and Biological Evaluation of gamma-Aminopropyl Silatrane
      Acyclovir Hybrids with Immunomodulatory Effects.
AB  - Several derivatives of gamma-aminopropyl silatrane containing acyclovir in their
      molecular structure were synthesized and evaluated for their immunomodulatory and
      antiviral activities. The structures of all these derivatives were confirmed by
      mass spectra, IR, and (1) H NMR. Based on WST-1 assay in vitro, these compounds
      could stimulate proliferation of splenic lymphocytes at certain concentrations.
      Furthermore, compound 3d could also potentiate the expression of IFN-gamma, IL-2,
      CD4(+) , CD8(+) , and CD4(+) /CD8(+) in vivo. Our results show that these
      derivatives possess antiviral activity against herpes simplex viruses with a
      similar potency to acyclovir without a cellular immune response. 

PMID- 25599976
TI  - Plasma biomarkers of pulmonary hypertension identified by Fourier transform
      infrared spectroscopy and principal component analysis.
AB  - The main goal of this study was to find specific plasma spectral markers
      associated with pulmonary arterial hypertension (PAH) induced by monocrotaline
      injection in rats. FTIR was used to monitor biochemical changes in plasma caused
      by PAH as compared with the systemic hypertension induced by partial ligation on
      the left artery and with the control group. Both pathologies, systemic and
      pulmonary hypertension, induced a unique response in the biochemical content of
      plasma, mainly related to the composition and secondary structure of plasma
      proteins. For PAH, beta-pleated sheet components of plasma proteins were
      identified whereas the protein composition in systemic hypertension was dominated
      by unordered structures. In addition, a higher concentration of tyrosine-rich
      proteins was found in plasma in PAH than in systemic hypertension. The
      differences between both pathologies were identified also in terms of lipid
      composition/metabolism as well as in the content of RNA and glucose, suggesting
      that lipid peroxidation appears upon pulmonary hypertension development. In
      summary, this work demonstrates that FTIR spectroscopy supported by principal
      component analysis (PCA) has the potential to become a fast and non-destructive
      method for biochemical characterization of plasma that consequently could have a
      diagnostic significance in pulmonary hypertension. 

PMID- 25599977
TI  - Layered exfoliable crystalline materials based on Sm-, Eu- and Eu/Gd-2
      phenylsuccinate frameworks. Crystal structure, topology and luminescence
      properties.
AB  - Three new layered metal-organic frameworks (MOFs) based on 2-phenylsuccinic acid
      (H2psa) and lanthanide ions with the formula [Ln2(C10H8O4)3(H2O)] (Ln = Eu, Sm
      and Eu-Gd) have been synthesized under solvothermal conditions and fully
      characterized by single-crystal X-ray diffraction, thermal and vibrational
      analyses. The compounds are isostructural featuring 2D frameworks that consist of
      infinite zigzag chains composed of [LnO8] and [LnO8(H2O)] edge-sharing polyhedra
      linked by psa ligands leading to layers further connected by weak pi-pi
      interactions in an edge orientation. Moreover, a topological study was carried
      out to obtain the simplified net for better comparison with structurally related
      compounds. The crystals were exfoliated into nanolayers after miniaturization by
      addition of sodium acetate as a capping agent in the reaction medium. Scanning
      electron microscopy was applied to characterize the miniaturized samples whereas
      the exfoliated hybrid nanosheets were studied by atomic force microscopy. The
      photoluminescence (PL) properties of the bulk compounds as well as the
      miniaturized and exfoliated materials were investigated and compared with other
      related ones. An exhaustive study of the Eu(iii)-based MOFs was performed on the
      basis of the obtained PL parameters (excitation and emission spectra, kr, knr,
      intrinsic quantum yields and lifetimes) to explore the underlying structure
      property relationships. 

PMID- 25599974
TI  - A genome-wide association study of early spontaneous preterm delivery.
AB  - Preterm birth is the leading cause of infant morbidity and mortality. Despite
      extensive research, the genetic contributions to spontaneous preterm birth (SPTB)
      are not well understood. Term controls were matched with cases by race/ethnicity,
      maternal age, and parity prior to recruitment. Genotyping was performed using
      Affymetrix SNP Array 6.0 assays. Statistical analyses utilized PLINK to compare
      allele occurrence rates between case and control groups, and incorporated quality
      control and multiple-testing adjustments. We analyzed DNA samples from mother
      infant pairs from early SPTB cases (20(0/7)-33(6/7) weeks, 959 women and 979
      neonates) and term delivery controls (39(0/7)-41(6/7) weeks, 960 women and 985
      neonates). For validation purposes, we included an independent validation cohort
      consisting of early SPTB cases (293 mothers and 243 infants) and term controls
      (200 mothers and 149 infants). Clustering analysis revealed no population
      stratification. Multiple maternal SNPs were identified with association P-values
      between 10*10(-5) and 10*10(-6). The most significant maternal SNP was rs17053026
      on chromosome 3 with an odds ratio (OR) 0.44 with a P-value of 1.0*10(-6). Two
      neonatal SNPs reached the genome-wide significance threshold, including
      rs17527054 on chromosome 6p22 with a P-value of 2.7*10(-12) and rs3777722 on
      chromosome 6q27 with a P-value of 1.4*10(-10). However, we could not replicate
      these findings after adjusting for multiple comparisons in a validation cohort.
      This is the first report of a genome-wide case-control study to identify single
      nucleotide polymorphisms (SNPs) that correlate with SPTB.

PMID- 25599978
TI  - Multi-channel wireless mapping of gastrointestinal serosal slow wave propagation.
AB  - BACKGROUND: High-resolution (HR) extracellular mapping allows accurate profiling
      of normal and dysrhythmic slow wave patterns. A current limitation is that cables
      traverse the abdominal wall or a natural orifice, risking discomfort,
      dislodgement or infection. Wireless approaches offer advantages, but a multi
      channel system is required, capable of recording slow waves and mapping
      propagation with high fidelity. METHODS: A novel multi-channel (n = 7) wireless
      mapping system was developed and compared to a wired commercial system. Slow wave
      signals were recorded from the porcine gastric and intestinal serosa in vivo.
      Signals were simultaneously acquired using both systems, and were filtered and
      processed to map activation wavefronts. For validation, the frequency and
      amplitude of detected events were compared, together with the speed and direction
      of mapped wavefronts. KEY RESULTS: The wireless device achieved comparable signal
      quality to the reference device, and slow wave frequencies were identical.
      Amplitudes of the acquired gastric and intestinal slow wave signals were
      consistent between the devices. During normal propagation, spatiotemporal mapping
      remained accurate in the wireless system, however, during ectopic dysrhythmic
      pacemaking, the lower sampling resolution of the wireless device led to reduced
      accuracy in spatiotemporal mapping. CONCLUSIONS & INFERENCES: A novel
      multichannel wireless device is presented for mapping slow wave activity. The
      device achieved high quality signals, and has the potential to facilitate chronic
      monitoring studies and clinical translation of spatiotemporal mapping. The
      current implementation may be applied to detect normal patterns and dysrhythmia
      onset, but HR mapping with finely spaced arrays currently remains necessary to
      accurately define dysrhythmic patterns.

PMID- 25599979
TI  - BOLD responses related to focal spikes and widespread bilateral synchronous
      discharges generated in the frontal lobe.
AB  - OBJECTIVE: To investigate whether specific frontal regions have a tendency to
      generate widespread bilateral synchronous discharges (WBSDs) and others focal
      spikes and to determine the regions most involved when WBSDs occur; to assess the
      relationships between the extent of electroencephalography (EEG) discharges and
      the extent of metabolic changes measured by EEG/functional magnetic resonance
      imaging (fMRI). METHODS: Thirty-seven patients with interictal epileptic
      discharges (IEDs) with frontocentral predominance underwent EEG/fMRI. Patients
      were divided into a Focal (20 patients) group with focal frontal spikes and a
      WBSD group (17 patients). Maps of hemodynamic responses related to IEDs were
      compared between the two groups. RESULTS: The mean number +/- SD of IEDs in the
      Focal group was 137.5 +/- 38.1 and in the WBSD group, 73.5 +/- 16.6 (p = 0.07).
      The volume of hemodynamic responses in the WBSD group was significantly larger
      than in the Focal group (mean, 243.3 +/- 41.1 versus 114.8 +/- 27.4 cm(3), p =
      0.01). Maximum hemodynamic responses occurred in both groups in the following
      regions: dorsolateral prefrontal, mesial prefrontal, cingulate, and supplementary
      motor cortices. Maxima in premotor and motor cortex, frontal operculum,
      frontopolar, and orbitofrontal regions were found only in the Focal group, and
      maxima in thalamus and caudate only occurred in the WBSD group. Thalamic
      responses were significantly more common in the WBSD group (14/17) than in the
      Focal group (7/20), p = 0.004. Deactivation in the default mode network was
      significantly more common in the WBSD group (14/17) than in the Focal group
      (10/20), p = 0.04. SIGNIFICANCE: The spatial distribution and extent of blood
      oxygen level-dependent (BOLD) responses correlate well with electrophysiologic
      changes. Focal frontal spikes and WBSDs are not region specific in the frontal
      lobe, and the same frontal region can generate focal and generalized discharges.
      This suggests that widespread discharges reflect widespread epileptogenicity
      rather than a focal discharge located in a region favorable to spreading. The
      thalamus plays an important role in bilateral synchronization.

PMID- 25599980
TI  - Transcription co-activator Arabidopsis ANGUSTIFOLIA3 (AN3) regulates water-use
      efficiency and drought tolerance by modulating stomatal density and improving
      root architecture by the transrepression of YODA (YDA).
AB  - One goal of modern agriculture is the improvement of plant drought tolerance and
      water-use efficiency (WUE). Although stomatal density has been linked to WUE, the
      causal molecular mechanisms and engineered alternations of this relationship are
      not yet fully understood. Moreover, YODA (YDA), which is a MAPKK kinase gene,
      negatively regulates stomatal development. BR-INSENSITIVE 2 interacts with
      phosphorylates and inhibits YDA. However, whether YDA is modulated in the
      transcriptional level is still unclear. Plants lacking ANGUSTIFOLIA3 (AN3)
      activity have high drought stress tolerance because of low stomatal densities and
      improved root architecture. Such plants also exhibit enhanced WUE through
      declining transpiration without a demonstrable reduction in biomass accumulation.
      AN3 negatively regulated YDA expression at the transcriptional level by target
      gene analysis. Chromatin immunoprecipitation analysis indicated that AN3 was
      associated with a region of the YDA promoter in vivo. YDA mutation significantly
      decreased the stomatal density and root length of an3 mutant, thus proving the
      participation of YDA in an3 drought tolerance and WUE enhancement. These
      components form an AN3-YDA complex, which allows the integration of water deficit
      stress signalling into the production or spacing of stomata and cell
      proliferation, thus leading to drought tolerance and enhanced WUE. 

PMID- 25599981
TI  - Klaus Mosbach tribute.

PMID- 25599983
TI  - Outcome of 12 antenatally diagnosed fetal arachnoid cysts: case series and review
      of the literature.
AB  - OBJECTIVES: To investigate the natural history, associated abnormalities and
      outcome of 12 fetuses with arachnoid cyst diagnosed antenatally by ultrasound and
      magnetic resonance imaging and to compare the outcome with cases in the
      literature. METHODS: A retrospective study of all cases of antenatally detected
      fetal arachnoid cysts was performed in patients referred to a tertiary unit
      between 2007 and 2013. Associated abnormalities, pregnancy outcome and postnatal
      follow-up were analyzed. All papers about prenatally diagnosed arachnoid cysts,
      of the last 30 years, were evaluated (search terms in Pubmed: "prenatal
      diagnosis", "Arachnoid Cysts"). RESULTS: Fetal arachnoid cysts were diagnosed in
      12 fetuses, 9 were females. The mean gestational age of diagnosis was 28 1/7
      (range 19 1/7-34 2/7 weeks). A total of 9 cases were supratentorial, 3 were
      located in the posterior fossa. In 10 cases a fetal MRI was performed which
      confirmed brain compression in 4 out of 5 supratentorial arachnoid cyst. MRI did
      not reveal other malformations nor signs of nodular heterotopia. Only one fetus
      presented with additional major anomalies (bilateral ventricumomegaly of >20 mm
      and rhombencephalosynapsis) leading to a termination of pregnancy. Two neonates
      underwent endoscopic fenestration of the arachnoid cyst in the first week of life
      with no additional intervention in childhood. All but one (10/11) had a favorable
      postnatal outcome. This child suffered from visual impairment at autism was
      diagnosed at the age of 5. One child had a surgical correction of strabismus
      later in childhood. In one child the infratentorial arachnoid cyst regressed
      spontaneously on ultrasound and MRI in the postnatal period. CONCLUSIONS: The
      majority of arachnoid cysts in this series are of benign origin and remain
      stable. Based on the current series and the review of the literature, in the
      absence of other associated anomalies and when the karyotype is normal, the
      postnatal overall and neurological outcome is favorable. Large suprasellar
      arachnoid cysts however, may cause visual impairment and endocrinological
      disturbances. Rarely associated cerebral or cerebellar malformations are present.
      Modern postnatal management of suprasellar arachnoid cyst consists of endoscopic
      cystoventriculostomy.

PMID- 25599982
TI  - Infant gut microbiota and food sensitization: associations in the first year of
      life.
AB  - BACKGROUND: The gut microbiota is established during infancy and plays a
      fundamental role in shaping host immunity. Colonization patterns may influence
      the development of atopic disease, but existing evidence is limited and
      conflicting. OBJECTIVE: To explore associations of infant gut microbiota and food
      sensitization. METHODS: Food sensitization at 1 year was determined by skin prick
      testing in 166 infants from the population-based Canadian Healthy Infant
      Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12
      months, and microbiota was characterized by Illumina 16S rRNA sequencing.
      RESULTS: Twelve infants (7.2%) were sensitized to >= 1 common food allergen at 1
      year. Enterobacteriaceae were overrepresented and Bacteroidaceae were
      underrepresented in the gut microbiota of food-sensitized infants at 3 months and
      1 year, whereas lower microbiota richness was evident only at 3 months. Each
      quartile increase in richness at 3 months was associated with a 55% reduction in
      risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence
      interval 0.23-0.87). Independently, each quartile increase in
      Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in
      risk (2.02, 1.07-3.80). These associations were upheld in a sensitivity analysis
      among infants who were vaginally delivered, exclusively breastfed and unexposed
      to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained
      elevated among sensitized infants, who also tended to have decreased abundance of
      Ruminococcaceae. CONCLUSIONS AND CLINICAL RELEVANCE: Low gut microbiota richness
      and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are
      associated with subsequent food sensitization, suggesting that early gut
      colonization may contribute to the development of atopic disease, including food
      allergy.

PMID- 25599984
TI  - Cancer Survivorship in Rural and Urban Adults: A Descriptive and Mixed Methods
      Study.
AB  - PURPOSE: Rural-dwelling cancer survivors (CSs) are at risk for decrements in
      health and well-being due to decreased access to health care and support
      resources. This study compares the impact of cancer in rural- and urban-dwelling
      adult CSs living in 2 regions of the Pacific Northwest. METHODS: A convenience
      sample of posttreatment adult CSs (N = 132) completed the Impact of Cancer
      version 2 (IOCv2) and the Memorial Symptom Assessment Scale-short form. High and
      low scorers on the IOCv2 participated in an in-depth interview (n = 19).
      FINDINGS: The sample was predominantly middle-aged (mean age 58) and female
      (84%). Mean time since treatment completion was 6.7 years. Cancer diagnoses
      represented included breast (56%), gynecologic (9%), lymphoma (8%), head and neck
      (6%), and colorectal (5%). Comparisons across geographic regions show
      statistically significant differences in body concerns, worry, negative impact,
      and employment concerns. Rural-urban differences from interview data include
      access to health care, care coordination, connecting/community, thinking about
      death and dying, public/private journey, and advocacy. CONCLUSION: The insights
      into the differences and similarities between rural and urban CSs challenge the
      prevalent assumptions about rural-dwelling CSs and their risk for negative
      outcomes. A common theme across the study findings was community. Access to
      health care may not be the driver of the survivorship experience. Findings can
      influence health care providers and survivorship program development, building on
      the strengths of both rural and urban living and the engagement of the
      survivorship community.

PMID- 25599985
TI  - Object naming in epilepsy and epilepsy surgery.
AB  - The ability to express oneself verbally is critical for success in academic,
      occupational, and social domains. Unfortunately, word-finding or "naming"
      difficulty is the most common cognitive complaint among individuals with temporal
      lobe epilepsy (TLE), and a substantial body of work over the past several decades
      has documented naming impairment in left (language-dominant) TLE, with further
      risk to naming ability following left temporal lobe resection for seizure
      control. With these findings well established, this paper reviews more recent
      work that has aimed to identify the neuroanatomical substrates of naming,
      understand how adverse structural and functional effects of TLE might impinge
      upon these brain regions, predict and potentially reduce the risk of
      postoperative naming decline, and begin to understand naming difficulty in TLE
      from a developmental perspective. Factors that have confounded interpretation and
      hindrances to progress are discussed, and suggestions are provided for improved
      empirical investigation and directions for future research. 

PMID- 25599986
TI  - Self-reported anxiety and sleep problems in people with epilepsy and their
      association with quality of life.
AB  - Comorbidities are common in epilepsy, and their role in quality of life (QOL) is
      receiving increasing scrutiny. Considerable attention has been focused on the
      role of depression, the most common comorbidity, with rather less attention paid
      to its frequent concomitant, anxiety, and other conditions known to be at
      increased prevalence among people with epilepsy (PWE) when compared to the
      general population. In this paper, we report findings from a UK-based survey in
      which we examined self-reporting of two common comorbidities, anxiety and sleep
      problems, factors associated with them, and their role in QOL in people with and
      without epilepsy. Data were obtained via mailed questionnaires, supplemented by
      an internet survey, from PWE and age- and gender-matched controls. Based on self
      reported symptoms, PWE were at higher risk of anxiety and sleep problems.
      Contributory factors for anxiety included poorer general health, worry about
      seizures, and self-reported antiepileptic drug (AED) side effects. Good social
      support emerged as protective for anxiety in PWE. Nighttime sleep problems were
      very common even in controls but were further elevated in PWE. Antiepileptic drug
      adverse events emerged as an important contributory factor for sleep problems.
      Trait anxiety emerged as significant for defining overall QOL, and its importance
      over state anxiety supports the notion of anxiety in PWE as a primarily premorbid
      condition. In contrast, sleep quality was not consistently predictive of QOL. Our
      study has important implications for clinical management, emphasizing the need
      for a holistic approach to address wider patient-reported problems as well as any
      epilepsy-specific ones. 

PMID- 25599987
TI  - Clinical characteristics of children and young adults with co-occurring autism
      spectrum disorder and epilepsy.
AB  - The association between autism spectrum disorder (ASD) and epilepsy has been
      described for decades, and yet we still lack the full understanding of this
      relationship both clinically and at the pathophysiologic level. This review
      evaluates the available data in the literature pertaining to the clinical
      characteristics of patients with autism spectrum disorder who develop epilepsy
      and, conversely, patients with epilepsy who develop autism spectrum disorder.
      Many studies demonstrate an increased risk of epilepsy in individuals with ASD,
      but rates vary widely. This variability is likely secondary to the different
      study methods employed, including the study population and definitions of the
      disorders. Established risk factors for an increased risk of epilepsy in patients
      with ASD include intellectual disability and female gender. There is some
      evidence of an increased risk of epilepsy associated with other factors such as
      ASD etiology (syndromic), severity of autistic features, developmental
      regression, and family history. No one epilepsy syndrome or seizure type has been
      associated, although focal or localization-related seizures are often reported.
      The age at seizure onset can vary from infancy to adulthood with some evidence of
      a bimodal age distribution. The severity and intractability of epilepsy in
      populations with ASD have not been well studied, and there is very little
      investigation of the role that epilepsy plays in the autism behavioral phenotype.
      There is evidence of abnormal EEGs (especially epileptiform abnormalities) in
      children with ASD even in the absence of clinical seizures, but very little is
      known about this phenomenon and what it means. The development of autism spectrum
      disorder in patients with epilepsy is less well studied, but there is evidence
      that the ASD risk is greater in those with epilepsy than in the general
      population. One of the risk factors is intellectual disability, and there is some
      evidence that the presence of a particular seizure type, infantile spasms, may
      increase risk, but some of the data are conflicting. We believe that one of the
      reasons that so little is known about this phenomenon is the lack of cross talk
      between researchers and clinicians alike in the two fields. We conclude that
      large systematic studies that employ strict ascertainment of samples using
      standardized definitions of both disorders, validated data collection tools, and
      appropriate longitudinal follow-up are needed to better shed light on certain
      clinical aspects of the comorbidity of ASD and epilepsy. Ideally, we could
      provide the optimal diagnostic and treatment services to these patients in a
      multidisciplinary setting with both epilepsy and neurobehavioral specialists.
      This article is part of a Special Issue entitled "Autism and Epilepsy". 

PMID- 25599988
TI  - Platelet microparticle: a sensitive physiological "fine tuning" balancing factor
      in health and disease.
AB  - Platelet microparticles (PMPs) have long been regarded as inert "platelet dusts".
      They have now taken a center stage on the clinical research scene of transfusion
      medicine, being actually seen as long-stretch hands of platelets that exert a
      physiological role beyond the initial site of activation. These 0.05 um to 0.8 um
      microvesicles, delimited by a phospholipidic bilayer, are released by platelet
      membranes following activation by agonists, complement activation, or high shear
      forces. They can also be generated as a result of platelets and megakaryocyte
      senescence or cytoskeletal abnormalities. PMPs may orchestrate a delicate
      hemostatic balance in health, and act as procoagulant vectors in diseases
      triggering thrombosis. Furthermore, through their potential cargo of growth
      factors, microRNA and various bioactive molecules, they may promote healing in
      health, but, on the other side of the coin, can act as pro-inflammatory carriers
      and may contribute to cancer growth as an actor of the platelet-cancer loop.
      Through their cellular interactions they also interplay with the immune system.
      Their capacity to be generated by shear forces and contact with surfaces during
      the processing of blood and blood components, which may trigger transfusion
      reactions, make them also an integral part of transfusion medicine. Given their
      documented association with pathological conditions, PMP may serve as biomarkers
      for disease status or as a possible new target for anti-platelet drugs to treat
      cancer or inflammation. 

PMID- 25599990
TI  - Welcome aboard.

PMID- 25599989
TI  - Factors associated with adoption of the electronic health record system among
      primary care physicians.
AB  - BACKGROUND: A territory-wide Internet-based electronic patient record allows
      better patient care in different sectors. The engagement of private physicians is
      one of the major facilitators for implementation, but there is limited
      information about the current adoption level of electronic medical record (eMR)
      among private primary care physicians. OBJECTIVE: This survey measured the
      adoption level, enabling factors, and hindering factors of eMR, among private
      physicians in Hong Kong. It also evaluated the key functions and the popularity
      of electronic systems and vendors used by these private practitioners. METHODS: A
      central registry consisting of 4324 private practitioners was set up. Invitations
      for self-administered surveys and the completed questionnaires were sent and
      returned via fax, email, postal mail, and on-site clinic visits. Current users
      and non-users of eMR system were compared according to their demographic and
      practice characteristics. Student's t tests and chi-square tests were used for
      continuous and categorical variables, respectively. RESULTS: A total of 524
      completed surveys (response rate 524/4405 11.90%) were collected. The proportion
      of using eMR in private clinics was 79.6% (417/524). When compared with non
      users, the eMR users were younger (users: 48.4 years SD 10.6 years vs non-users:
      61.7 years SD 10.2 years, P<.001); more were female physicians (users: 80/417,
      19.2% vs non-users: 14/107, 13.1%, P=.013); possessed less clinical experience
      (with more than20 years of practice: users: 261/417, 62.6% vs non-user: 93/107,
      86.9%, P<.001); fewer worked under a Health Maintenance Organization (users:
      347/417, 83.2% vs non-users: 97/107, 90.7%, P<.001) and more worked with practice
      partners (users: 126/417, 30.2% vs non-users: 4/107, 3.7%, P<.001). Efficiency
      (379/417, 90.9%) and reduction of medical errors (229/417, 54.9%) were the major
      enabling factors, while patient-unfriendliness (58/107, 54.2%) and limited
      consultation time (54/107, 50.5%) were the most commonly reported hindering
      factors. The key functions of computer software among eMR users consisted of
      electronic patient registration system (376/417, 90.2%), drug dispensing system
      (328/417, 78.7%) and electronic drug labels (296/417, 71.0%). SoftLink Clinic
      Solution was the most popular vendor (160/417, 38.4%). CONCLUSIONS: These
      findings identified several physician groups who should be targeted for more
      assistance on eMR installation and its adoption. Future studies should address
      the barriers of using Internet-based eMR to enhance its adoption.

PMID- 25599991
TI  - Health information exchange implementation: lessons learned and critical success
      factors from a case study.
AB  - BACKGROUND: Much attention has been given to the proposition that the exchange of
      health information as an act, and health information exchange (HIE), as an
      entity, are critical components of a framework for health care change, yet little
      has been studied to understand the value proposition of implementing HIE with a
      statewide HIE. Such an organization facilitates the exchange of health
      information across disparate systems, thus following patients as they move across
      different care settings and encounters, whether or not they share an
      organizational affiliation. A sociotechnical systems approach and an
      interorganizational systems framework were used to examine implementation of a
      health system electronic medical record (EMR) system onto a statewide HIE, under
      a cooperative agreement with the Office of the National Coordinator for Health
      Information Technology, and its collaborating organizations. OBJECTIVE: The
      objective of the study was to focus on the implementation of a health system onto
      a statewide HIE; provide insight into the technical, organizational, and
      governance aspects of a large private health system and the Virginia statewide
      HIE (organizations with the shared goal of exchanging health information); and to
      understand the organizational motivations and value propositions apparent during
      HIE implementation. METHODS: We used a formative evaluation methodology to
      investigate the first implementation of a health system onto the statewide HIE.
      Qualitative methods (direct observation, 36 hours), informal information
      gathering, semistructured interviews (N=12), and document analysis were used to
      gather data between August 12, 2012 and June 24, 2013. Derived from
      sociotechnical concepts, a Blended Value Collaboration Enactment Framework guided
      the data gathering and analysis to understand organizational stakeholders'
      perspectives across technical, organizational, and governance dimensions.
      RESULTS: Several challenges, successes, and lessons learned during the
      implementation of a health system to the statewide HIE were found. The most
      significant perceived success was accomplishing the implementation, although many
      interviewees also underscored the value of a project champion with decision
      making power. In terms of lessons learned, social reasons were found to be very
      significant motivators for early implementation, frequently outweighing economic
      motivations. It was clear that understanding the guides early in the project
      would have mitigated some of the challenges that emerged, and early communication
      with the electronic health record vendor so that they have a solid understanding
      of the undertaking was critical. An HIE implementations evaluation framework was
      found to be useful for assessing challenges, motivations, value propositions for
      participating, and success factors to consider for future implementations.
      CONCLUSIONS: This case study illuminates five critical success factors for
      implementation of a health system onto a statewide HIE. This study also reveals
      that organizations have varied motivations and value proposition perceptions for
      engaging in the exchange of health information, few of which, at the early
      stages, are economically driven.

PMID- 25599993
TI  - Commensal microbiota influence systemic autoimmune responses.
AB  - Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases,
      including systemic lupus erythematosus and systemic sclerosis. However, the
      processes underlying the loss of tolerance against nuclear self-constituents
      remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we
      report that approximately 25% of mice lacking secondary lymphoid organs
      spontaneously develop specific antinuclear antibodies. Interestingly, we find
      this phenotype is not caused by a defect in central tolerance. Rather, cell
      specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune
      responses to the formation of gut-associated lymphoid tissue in the neonatal
      period of life. We further demonstrate antinuclear antibody production is
      influenced by the presence of commensal gut flora, in particular increased
      colonization with segmented filamentous bacteria, and IL-17 receptor signaling.
      Together, these data indicate that neonatal colonization of gut microbiota
      influences generalized autoimmunity in adult life. 

PMID- 25599992
TI  - Nuclear matrix protein Matrin3 regulates alternative splicing and forms
      overlapping regulatory networks with PTB.
AB  - Matrin3 is an RNA- and DNA-binding nuclear matrix protein found to be associated
      with neural and muscular degenerative diseases. A number of possible functions of
      Matrin3 have been suggested, but no widespread role in RNA metabolism has yet
      been clearly demonstrated. We identified Matrin3 by its interaction with the
      second RRM domain of the splicing regulator PTB. Using a combination of RNAi
      knockdown, transcriptome profiling and iCLIP, we find that Matrin3 is a regulator
      of hundreds of alternative splicing events, principally acting as a splicing
      repressor with only a small proportion of targeted events being co-regulated by
      PTB. In contrast to other splicing regulators, Matrin3 binds to an extended
      region within repressed exons and flanking introns with no sharply defined peaks.
      The identification of this clear molecular function of Matrin3 should help to
      clarify the molecular pathology of ALS and other diseases caused by mutations of
      Matrin3. 

PMID- 25599994
TI  - Effects of X-ray and carbon ion beam irradiation on membrane permeability and
      integrity in Saccharomyces cerevisiae cells.
AB  - Saccharomyces cerevisiae has served as a eukaryotic model in radiation biology
      studies of cellular responses to ionizing radiation (IR). Research in this field
      has thus far mainly been focused on DNA strand breaks, DNA base damage, or
      inhibition of protein activity. However, the effects of IR on S. cerevisiae cell
      membranes have barely been studied. Here, we investigated the changes in the
      permeability and integrity of S. cerevisiae cell membranes induced by high-linear
      energy transfer carbon ion (CI) beam or low-linear energy transfer X-ray. After
      CI exposure, protein elution and nucleotide diffusion were more pronounced than
      after X-ray treatment at the same doses, although these features were most
      prevalent following irradiation doses of 25-175 Gy. Flow cytometry of forward
      scatter light versus side scatter light and double-staining with fluorescein
      diacetate and propidium iodide showed that CI and X-ray irradiation significantly
      affected S. cerevisiae cell membrane integrity and cellular enzyme activity
      compared with untreated control cells. The extent of lesions in CI-irradiated
      cells, which exhibited markedly altered morphology and size, was greater than
      that in X-ray-irradiated cells. The relationships between permeabilized cells,
      esterase activity, and non-viable cell numbers furthermore indicated that
      irradiation-induced increases in cell permeabilization and decreases in esterase
      activity are dependent on the type of radiation and that these parameters
      correspond well with cell viability. These results also indicate that the
      patterns of cell inactivity due to X-ray or CI irradiation may be similar in
      terms of cell membrane damage. 

PMID- 25599997
TI  - Risk factors for the mortality of trauma victims in the intensive care unit.
AB  - OBJECTIVE: To identify the risk factors associated with mortality of trauma
      victims during hospitalisation in the intensive care unit (ICU). DESIGN:
      Prospective cohort. SETTING: Brazilian ICU specialising in the care of trauma
      victims. METHODS: The subjects were divided into two groups: survivors and non
      survivors. The variables used to compare the groups included demographic and
      clinical characteristics and illness/injury severity (Acute Physiology and
      Chronic Health Evaluation [APACHE II], Simplified Acute Physiology Score [SAPS
      II], Logistic Organ Dysfunction System [LODS], Injury Severity Score [ISS] and
      New Injury Severity Score [NISS]). The data were analysed using descriptive and
      inferential statistics and multiple logistic regression analysis. RESULTS: The
      sample consisted of 200 patients (164 males) with a mean age of 40.7 years. The
      predominant causes of injury were traffic accidents (57.5%) followed by falls
      (31.0%). The ICU mortality was 19.0%. Logistic regression analysis revealed that
      one point on the NISS and SAPS II scores increased the risk of death by 6% and
      7%, respectively. In contrast, the risk of dying decreased 4% for each day of ICU
      hospitalisation. CONCLUSION: Professionals must use the SAPS II and NISS for the
      early identification of trauma victims at high risk for death especially during
      the first days of ICU hospitalisation.

PMID- 25599995
TI  - Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam
      irradiation in the non-small-cell lung cancer cell line H460.
AB  - The present study investigated the ability of carboplatin and paclitaxel to
      sensitize human non-small-cell lung cancer (NSCLC) cells to carbon-ion beam
      irradiation. NSCLC H460 cells treated with carboplatin or paclitaxel were
      irradiated with X-rays or carbon-ion beams, and radiosensitivity was evaluated by
      clonogenic survival assay. Cell proliferation was determined by counting the
      number of viable cells using Trypan blue. Apoptosis and senescence were evaluated
      by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)
      staining and senescence-associated beta-galactosidase (SA-beta-gal) staining,
      respectively. The expression of cleaved caspase-3, Bax, p53 and p21 was analyzed
      by western blotting. Clonogenic survival assays demonstrated a synergistic
      radiosensitizing effect of carboplatin and paclitaxel with carbon-ion beams; the
      sensitizer enhancement ratios (SERs) at the dose giving a 10% survival fraction
      (D10) were 1.21 and 1.22, respectively. Similarly, carboplatin and paclitaxel
      showed a radiosensitizing effect with X-rays; the SERs were 1.41 and 1.29,
      respectively. Cell proliferation assays validated the radiosensitizing effect of
      carboplatin and paclitaxel with both carbon-ion beam and X-ray irradiation.
      Carboplatin and paclitaxel treatment combined with carbon-ion beams increased
      TUNEL-positive cells and the expression of cleaved caspase-3 and Bax, indicating
      the enhancement of apoptosis. The combined treatment also increased SA-beta-gal
      positive cells and the expression of p53 and p21, indicating the enhancement of
      senescence. In summary, carboplatin and paclitaxel radiosensitized H460 cells to
      carbon-ion beam irradiation by enhancing irradiation-induced apoptosis and
      senescence. 

PMID- 25599999
TI  - Paliperidone palmitate use in pregnancy in a woman with schizophrenia.
AB  - Long-acting antipsychotic use in schizophrenia has become an advantage for
      treatment compliance and convenient administration of the drugs. There is no data
      on paliperidone palmitate (PP) use in pregnancy, which is the longest-acting
      (i.e., 1 month) atypical antipsychotic. In this case report, we aim to present a
      patient diagnosed with schizophrenia who had been using PP before and during her
      pregnancy until week 28 of gestation and gave birth to a male baby that weighed
      3000 g at 39 weeks. As far as we know, this is the first case report on PP use
      during pregnancy. 

PMID- 25599996
TI  - Clinical experience of volumetric modulated arc therapy for malignant pleural
      mesothelioma after extrapleural pneumonectomy.
AB  - The purpose of this study was to evaluate the efficacy and safety of volumetric
      modulated arc therapy (VMAT) after extrapleural pneumonectomy (EPP) in patients
      with malignant pleural mesothelioma (MPM). A total of 15 patients who received
      VMAT after EPP were enrolled. All patients were males, and the median age was 67
      years (Stage IB in two, II in six, and III in seven patients). The clinical
      target volume (CTV) included the entire preoperative ipsilateral hemithorax and
      involved nodal stations. The CTV was generally expanded by 10-15 mm beyond the
      planning target volume (PTV). The dose prescription was designed to cover 95% of
      the PTV with 54 Gy in 30 fractions. The median follow-up period was 11 months.
      Treatment-related toxicities were evaluated by Common Terminology Criteria for
      Adverse Events (CTCAE) ver. 4. One-year local control, disease-free survival, and
      overall survival rates were 55.7% [95% confidence interval (CI): 25.6-85.8%],
      29.3% (95% CI: 5.3-53.3%), and 43.1% (95% CI: 17.1-69.0%), respectively.
      According to the histological analysis, the one-year LC rate was significantly
      worse in patients with non-epithelial type (biphasic and sarcomatoid types) than
      in patients with epithelial type [epithelial type: 83.3% (95% CI, 53.5-100%), non
      epithelial type: 0% (95% CI, 0%), P = 0.0011]. Grade 3 pneumonitis after VMAT was
      observed in three patients (20.0%); however, no patients died of pulmonary
      toxicity. VMAT appears to be relatively safe for patients with MPM after EPP
      because of the low pulmonary dose. 

PMID- 25599998
TI  - How accurate is the AVPU scale in detecting neurological impairment when used by
      general ward nurses? An evaluation study using simulation and a questionnaire.
AB  - OBJECTIVES: to evaluate accuracy, sensitivity, specificity and inter-rater
      agreement of AVPU (Alert, Voice, Pain, Unresponsive) when used by non-specialist
      nursing staff assessing consciousness, and to investigate users' views. METHODS:
      Video-recorded simulations of assessments of consciousness were developed and
      verified by an expert panel. Participants scored simulations using AVPU and
      completed questionnaires eliciting views on the scale. AVPU scores were compared
      with functional levels agreed by the panel. SETTING: A large urban teaching
      hospital. RESULTS: Fifty-one participants scored 255 simulations. Overall
      accuracy was 82.4% (95% CI=77.7-87.1%), sensitivity 0.94 (95% CI=0.90-0.98),
      specificity 0.74 (95% CI=0.66-0.82) and inter-rater agreement (un-weighted kappa)
      0.782. Accuracy was low for simulations depicting an orientated patient whose
      eyes open to speech (49% correct) and a confused patient with spontaneous eye
      opening (61.5% correct). Sensitivity and agreement for levels corresponding to
      "Alert" and "Voice" were 0.81 (95% CI=0.69-0.93) and kappa=0.506. Participants
      expressed uncertainty about aspects of AVPU's use. CONCLUSIONS: AVPU had low
      rates of accuracy, sensitivity and agreement in distinguishing between "Alert"
      and "Voice", and low specificity overall, suggesting it may be unsuitable for
      early warning scoring. Participants expressed doubts about the use of AVPU.

PMID- 25600001
TI  - Strain-induced significant increase in metal-insulator transition temperature in
      oxygen-deficient Fe oxide epitaxial thin films.
AB  - Oxygen coordination of transition metals is a key for functional properties of
      transition-metal oxides, because hybridization of transition-metal d and oxygen p
      orbitals determines correlations between charges, spins and lattices. Strain
      often modifies the oxygen coordination environment and affects such correlations
      in the oxides, resulting in the emergence of unusual properties and, in some
      cases, fascinating behaviors. While these strain effects have been studied in
      many of the fully-oxygenated oxides, such as ABO3 perovskites, those in oxygen
      deficient oxides consisting of various oxygen coordination environments like
      tetrahedra and pyramids as well as octahedra remain unexplored. Here we report on
      the discovery of a strain-induced significant increase, by 550 K, in the metal
      insulator transition temperature of an oxygen-deficient Fe oxide epitaxial thin
      film. The observed transition at 620 K is ascribed to charge disproportionation
      of Fe(3.66+) into Fe(4+) and Fe(3+), associated with oxygen-vacancy ordering. The
      significant increase in the metal-insulator transition temperature, from 70 K in
      the bulk material, demonstrates that epitaxial growth of oxygen-deficient oxides
      under substrate-induced strain is a promising route for exploring novel
      functionality.

PMID- 25600002
TI  - Probing the limits of gate-based charge sensing.
AB  - Quantum computation requires a qubit-specific measurement capability to readout
      the final state of individual qubits. Promising solid-state architectures use
      external readout electrometers but these can be replaced by a more compact
      readout element, an in situ gate sensor. Gate-sensing couples the qubit to a
      resonant circuit via a gate and probes the qubit's radiofrequency polarizability.
      Here we investigate the ultimate performance of such a resonant readout scheme
      and the noise sources that limit its operation. We find a charge sensitivity of
      37 MUe Hz(-1/2), the best value reported for this technique, using the example of
      a gate sensor strongly coupled to a double quantum dot at the corner states of a
      silicon nanowire transistor. We discuss the experimental factors limiting gate
      detection and highlight ways to optimize its sensitivity. In total, resonant gate
      based readout has advantages over external electrometers both in terms of
      reduction of circuit elements as well as absolute charge sensitivity. 

PMID- 25600003
TI  - Fluorescence turn-on chemosensor for highly selective and sensitive detection and
      bioimaging of Al(3+) in living cells based on ion-induced aggregation.
AB  - Herein, a new fluorescence turn-on chemosensor 2-(4-(1,2,2
      triphenylvinyl)phenoxy)acetic acid (TPE-COOH) specific for Al(3+) was presented
      by combining the aggregation-induced-emission (AIE) effect of tertaphenylethylene
      and the complexation capability of carboxyl. The introduction of carboxylic group
      provides the probe with good water-solubility which is important for analyzing
      biological samples. The recognition toward Al(3+) induced the molecular
      aggregation and activated the blue fluorescence of the TPE core. The high
      selectivity of the probe was demonstrated by discriminating Al(3+) over a variety
      of metal ions in a complex mixture. A detection limit down to 21.6 nM was
      determined for Al(3+) quantitation. Furthermore, benefiting from its good water
      solubility and biocompatibility, imaging detection and real-time monitoring of
      Al(3+) in living HeLa cells were successfully achieved. The AIE effect of the
      probe enables high signal-to-noise ratio for bioimaging even without multiple
      washing steps. These superiorities make this probe a great potential for the
      functional study and analysis of Al(3+) in complex biosystems. 

PMID- 25600004
TI  - Visualising the distribution of individuals of advanced age in Canada: linking
      census data to maps.
AB  - OBJECTIVE: to link publically available aggregate census data to maps to visually
      convey information about the geographic distribution of those of advanced age in
      Canada. METHOD: we obtained aggregate statistics derived from the most recent
      2011 Canadian census data. We calculated the Percentage of People 90 Years of Age
      or Older and the Longevity Index in each of the 292 census divisions. The data
      and the Canadian census division map were merged to create thematic maps using
      Google Fusion Tables. RESULTS: overall, there were 217,930 women and men who were
      90 years of age or older in Canada in 2011. The regions with the highest
      proportion of elderly residents are in the south, rather than in the north of
      Canada. Southern Saskatchewan and southern Manitoba emerged as high longevity
      areas based on both indices. CONCLUSIONS: publically available data and free
      online tools can be used to create maps that visually display the geographic
      distribution of the oldest population across Canada. This approach provides an
      efficient way to observe patterns, identify adjacencies and perceive information
      that may not have been anticipated. This approach can be replicated in other
      jurisdictions using publically available data.

PMID- 25600005
TI  - Re: Issues concerning sarcopenia in ageing adults.

PMID- 25600006
TI  - Issues concerning sarcopenia in ageing adults.

PMID- 25600007
TI  - ABO blood types and cancer risk--a cohort study of 339,432 subjects in Taiwan.
AB  - BACKGROUND: The associations of laboratory-based ABO phenotypes with cancer risks
      and mortality have not been systematically determined. METHODS: The study
      subjects were 339,432 healthy individuals with laboratory-based blood types from
      a Taiwan cohort. RESULTS: Compared to blood type O, blood type A was
      significantly associated with an elevated risk of stomach cancer incidence
      (Hazard Ratio [HR], 1.38 [95% CI, 1.11-1.72]) and mortality (HR, 1.38 [95% CI,
      1.02-1.86]) compared with blood type O, after adjusting for age, sex, education,
      smoking, alcohol drinking, physical activity, and body mass index. Non-O blood
      types were associated with an elevated risk of pancreatic cancer, with blood type
      B reaching statistical significance for incidence (HR, 1.59 [95% CI, 1.02-2.48])
      and mortality (HR, 1.63 [95% CI, 1.02-2.60]). In contrast, kidney cancer risk was
      inversely associated with blood type AB (HR, 0.41 [95% CI, 0.18-0.93]) compared
      to type O. CONCLUSION: Cancer risks vary in people with different ABO blood
      types, with elevated risks of stomach cancer associated with blood type A and
      pancreatic cancer associated with non-O blood types (A, B, and AB).

PMID- 25600009
TI  - Editorial comment to Renal sinus exposure as an independent factor predicting
      asymptomatic unruptured pseudoaneurysm formation detected in the early
      postoperative period after minimally invasive partial nephrectomy.

PMID- 25600008
TI  - Isoform-specific expression of the neuropeptide orcokinin in Drosophila
      melanogaster.
AB  - Orcokinins are neuropeptides that have been identified in diverse arthropods. In
      some species, an orcokinin gene encodes two isoforms of mature orcokinin peptide
      through alternative mRNA splicing. The existence of two orcokinin isoforms was
      predicted in Drosophila melanogaster as well, but the expression pattern of both
      isoforms has not been characterized. Here, we use in situ hybridization, antibody
      staining, and enhancer fusion GAL4 transgenic flies to examine the expression
      patterns of the A and B forms of orcokinin, and provide evidence that they are
      expressed differentially in the central nervous system (CNS) and the intestinal
      enteroendocrine system. The orcokinin A isoform is mainly expressed in the CNS of
      both larvae and adults. The A form is expressed in 5 pairs of neurons in
      abdominal neuromeres 1-5 of the larval CNS. In the adult brain, the A form is
      expressed in one pair of neurons in the posteriorlateral protocerebrum, and an
      additional four pairs of neurons located near the basement of the accessory
      medulla. Orcokinin A expression is also observed in two pairs of neurons in the
      ventral nerve cord (VNC). The orcokinin B form is mainly expressed in intestinal
      enteroendocrine cells in the larva and adult, with additional expression in one
      unpaired neuron in the adult abdominal ganglion. Together, our results provide
      elucidation of the existence and differential expression of the two orcokinin
      isoforms in the Drosophila brain and gut, setting the stage for future functional
      studies of orcokinins utilizing the genetically amenable fly model. 

PMID- 25600010
TI  - Anaerobic co-digestion of sewage sludge and sugar beet pulp lixiviation in batch
      reactors: effect of temperature.
AB  - The feasibility of anaerobic co-digestion of sewage sludge (SS) and sugar beet
      pulp lixiviation (SBPL) was assessed. Mesophilic and thermophilic batch assays of
      five different SS/SBPL ratios were used to investigate the effect of temperature,
      providing basic data on methane yield and reduction in total volatiles. Microbe
      concentrations (Eubacteria and methanogenic Archaea) were linked to traditional
      parameters, namely biogas production and removal of total volatile solids (TVS).
      The relationship between Eubacteria and Archaea was analysed. Given equal masses
      of organic matter, net methane generation was higher in the mesophilic range on
      the biochemical methane potential (BMP) test. Methane yield, TVS removal data and
      high levels of volatile fatty acids provided further evidence of the best
      behaviour of the mesophilic range. At the end of testing the microbial population
      under of the reactors consisted of Eubacteria and Archaea, with Eubacteria
      predominant in all cases. 

PMID- 25600012
TI  - Batch and continuous biogas production arising from feed varying in rice straw
      volumes following pre-treatment with extrusion.
AB  - This paper studies the synergistic effects on biogas production obtained when
      different feedstocks are co-digested with varying proportions of rice straw and
      explores their behavior at the laboratory scale in continuously stirred
      digesters. Evaluative measures included methane production, volatile solids
      degradation, ash accumulation, and extrusion effectiveness. The effect of
      extrusion on the production of energy was also investigated. Results indicated
      that continuous stirred digesters fed with substrates composed of 10% or 30% of
      ensiled rice straw (on total FM) produced 146.1 and 140.0lNCH4kgDM(-1)day(-1),
      respectively. When extrusion was employed, organic matter degradation was
      promoted and methane production was significantly raised-by as much as 16%. For
      the feeds containing 10% rice straw, the increase in obtained energy was higher
      than the energy needed for the extrusion, but the energy balance was close to
      zero when the percentage of rice straw was the 30% of the feed. 

PMID- 25600011
TI  - Combination of upflow anaerobic sludge blanket (UASB) reactor and partial
      nitritation/anammox moving bed biofilm reactor (MBBR) for municipal wastewater
      treatment.
AB  - In this study the combination of an upflow anaerobic sludge blanket (UASB)
      reactor and a deammonification moving bed biofilm reactor (MBBR) for mainstream
      wastewater treatment was tested. The competition between aerobic ammonium
      oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) was studied during
      a 5months period of transition from reject water to mainstream wastewater
      followed by a 16months period of mainstream wastewater treatment. The decrease of
      influent ammonium concentration led to a wash-out of suspended biomass which had
      a major contribution to nitrite production. Influence of a dissolved oxygen
      concentration and a transient anoxia mechanism of NOB suppression were studied.
      It was shown that anoxic phase duration has no effect on NOB metabolism recovery
      and oxygen diffusion rather than affinities of AOB and NOB to oxygen determine
      the rate of nitrogen conversion in a biofilm system. Anammox activity remained on
      the level comparable to reject water treatment systems. 

PMID- 25600015
TI  - [Violence and social sciences. Advocacy for a methodological connection].

PMID- 25600014
TI  - Efficient poly(3-hydroxypropionate) production from glycerol using Lactobacillus
      reuteri and recombinant Escherichia coli harboring L. reuteri propionaldehyde
      dehydrogenase and Chromobacterium sp. PHA synthase genes.
AB  - Poly(3-hydroxypropionate), P(3HP), is a polymer combining good biodegradability
      with favorable material properties. In the present study, a production system for
      P(3HP) was designed, comprising conversion of glycerol to 3
      hydroxypropionaldehyde (3HPA) as equilibrium mixture with 3HPA-hydrate and -dimer
      in aqueous system (reuterin) using resting cells of native Lactobacillus reuteri
      in a first stage followed by transformation of the 3HPA to P(3HP) using
      recombinant Escherichia coli strain co-expressing highly active coenzyme A
      acylating propionaldehyde dehydrogenase (PduP) from L. reuteri and
      polyhydroxyalkanoate synthase (PhaCcs) from Chromobacterium sp. P(3HP) content of
      up to 40% (w/w) cell dry weight was reached, and the yield with respect to the
      reuterin consumed by the cells was 78%. Short biotransformation period (4.5h),
      lack of additives or expensive cofactors, and use of a cheap medium for
      cultivation of the recombinant strain, provides a new efficient and potentially
      economical system for P(3HP) production. 

PMID- 25600013
TI  - Biofuel potential of the newly isolated microalgae Acutodesmus dimorphus under
      temperature induced oxidative stress conditions.
AB  - Lack of control over temperature is one of the major issues in large scale
      cultivation of microalgae. Therefore, it is important to evaluate the effects of
      cultivation temperature on the growth and physiology of microalgae. In the
      present study, freshwater microalgae Acutodesmus dimorphus was grown at different
      temperature in continuous and two stage cultivation. Results revealed that during
      continuous cultivation A. dimorphus grows better at 35 degrees C than at 25
      degrees C and 38 degrees C. At 35 degrees C, A. dimorphus produced 22.7% lipid
      (containing 59% neutral lipid) and 33.7% carbohydrate along with 68% increase in
      biomass productivity (23.53mg/L/day) compared to 25 degrees C grown culture.
      Stress biomarkers like reactive oxygen species, antioxidant enzymes like catalase
      and ascorbate peroxidase and lipid peroxidation were also lowest in 35 degrees C
      grown culture which reveals that A. dimorphus is well acclimatized at 35 degrees
      C. 

PMID- 25600016
TI  - [Social order, legitimacy, and physical violence as a social fact].
AB  - The article discusses theoretical as well as methodological issues of a general
      sociology of violence which aims at focusing on the dynamic relationship between
      social order, legitimacy, and physical violence. The article argues in favor of a
      relational approach consisting of a realistic appraisal (in an epistemological
      sense) of the actors' place in a locally ordered setting of relationships among
      objectified forms of social order, collective identities, and social interaction.
      The author's long term research objective is to develop a general sociology of
      violence grounded in social action theory, to form a basis for exploring the
      phenomena of physical violence in the neo-Durkheimian sense as social facts. 

PMID- 25600017
TI  - The secret society and the social dynamics of terrorist behavior.
AB  - The article argues that individualist accounts cannot adequately explain the
      social dynamics of terrorist behavior as they turn analyses of terrorism into
      analyses of terrorists. A relational approach that concentrates on the social
      relations between terrorist organizations and their members would be able to do
      this, however. Therefore, the article presents a formal analysis that makes the
      "secret society" of terrorists the lynchpin of an explanation of how terrorist
      organizations shape the behavioral conditions of volunteers and suicide
      terrorists in a manner that triggers a type of behavior we might call terrorism. 

PMID- 25600018
TI  - When "the facts" become a text reinterpreting war with Serbian war veterans.
AB  - Rationalist theories of political violence proclaim rather than show what
      motivates war participation. This article tries to examine the limits of
      reconstructions of these motivations by analyzing interview material gathered
      from Serbian war veterans. Using "grounded theory" as a methodology, this
      research has revealed that the identification of motivations has to take into
      account social and historical contexts that play out as life-worlds and world
      views. Real decision points are, however, hard to identify. Therefore, the
      article suggests a stronger focus on "carriers" (Tragerschichten) for the study
      of conflict dynamics. 

PMID- 25600019
TI  - [Social order, stability, and certainty violence and social power in early modern
      history].
AB  - This article develops a comprehensive critique of historical research focussing
      on the mutual relations between social power and violence. According to the
      methodological initial hypothesis, due to the inadequate distinction between
      indigenious concept (from sources) and heuristic (from reseach) in the historical
      sciences, there have been very few valuable insights into these relations to
      date. In order to expand the research focus which is the objective of this
      article, the analysis draws on the two actor-centric reference systems of
      "certainty" and "order". The key idea behind this, operationalizing
      certainty/uncertainty by means of order/disorder, is a promising way of
      programmatically combining a vertical and horizontal network of relationships of
      power, violence, certainty, and order. 

PMID- 25600021
TI  - Legacy soil contamination at abandoned mine sites: making a case for guidance on
      soil protection.
AB  - Within the European Union, guidance in the form of a uniform Soil Directive does
      not exist and member states are left to enact their own legislation governing
      historic soil contamination. Several historic or "legacy" sites exist in Cyprus -
      an EU member state with a long history of mining and a significant number of
      abandoned mining sites. The gold-silver enrichment plant of Mitsero village was
      abandoned 70 years ago, yet soil samples inside and outside the plant were
      extremely low in pH, exhibited high leachability of heavy metals and high cyanide
      levels. Water samples collected from an ephemeral stream located down-gradient of
      the site contained high levels of heavy metals. Two abandoned open-pit mines
      (Kokkinopezoula and Mathiatis) were investigated, where elevated metal content in
      soil samples from the surrounding streams and spoil heaps, and extremely low pH
      and high metal content in water samples from the mine crater were measured.

PMID- 25600022
TI  - Prognostic value of systemic inflammatory responses in patients with upper
      urinary tract urothelial carcinoma.
AB  - PURPOSE: To determine the utility of systemic inflammatory response and develop a
      model based on serum inflammatory indices to aid prognostication in patients with
      upper urinary tract urothelial carcinoma (UTUC). METHODS: The study population
      comprised 277 patients with non-metastatic UTUC who underwent nephroureterectomy
      between 1999 and 2010. Multivariate survival analysis was performed using Cox's
      proportional hazards model, and a new model was developed to predict recurrence
      free (RFS) and disease-specific survival (DSS). The factors considered, in
      relation to systemic inflammatory responses, were as follows: albumin, white
      blood cell count, neutrophil count, lymphocyte count, red blood cell count, serum
      creatinine level, platelet count, prognostic nutritional index,
      platelet/lymphocyte ratio, neutrophil/lymphocyte ratio (NLR), and derived NLR.
      RESULTS: The final model consisted of bladder cuffing, pathologic T stage,
      lymphovascular invasion, and derived NLR. The bootstrap-concordance indices of
      the model were 0.778 [95 confidence interval (CI) 0.730-0.826] for RFS and 0.802
      (95 % CI 0.752-0.851) for DSS, respectively, and integrated area under the curve
      value for time to RFS and DSS for patients was 0.738 and 0.760, respectively.
      When we generated calibration curves, the nomograms were reasonably calibrated.
      CONCLUSIONS: Derived NLR may be used in combination with conventional staging
      techniques and other clinicopathological parameters to improve the prediction of
      survival in patients with UTUC.

PMID- 25600024
TI  - Mother as a vector of Salmonella enterica serotype Newport outbreak in a neonatal
      unit.
AB  - INTRODUCTION: In neonatal units, Salmonella infections have been attributed to
      food-borne sources and person to person transmission. METHODS: The outbreak
      described is the first reported by Salmonella enterica serotype Newport in a
      neonatal facility in Spain. RESULTS: The index case was an 8-day premature
      newborn that developed clinical sepsis with positive blood cultures. The outbreak
      source was the mother of the index case. CONCLUSIONS: It is essential to improve
      infection control measures taking into account the parents, as they can be an
      important source of infection.

PMID- 25600025
TI  - Development and evaluation of an automatic tumor segmentation tool: a comparison
      between automatic, semi-automatic and manual segmentation of mandibular
      odontogenic cysts and tumors.
AB  - INTRODUCTION: In the treatment of cancer in the head and neck region, computer
      assisted surgery can be used to estimate location and extent by segmentation of
      the tumor. This article presents a new tool (Smartbrush), which allows for faster
      automated segmentation of the tumor. METHODS: This new method was compared with
      other well-known techniques of segmentation. Thirty-eight patients with
      keratocystic odontogenic tumors were included in this study. The tumors were
      segmented using manual segmentation, threshold-based segmentation and
      segmentation using Smartbrush. All three methods were compared concerning
      usability, time expenditure and accuracy. RESULTS: The results suggest that
      segmentation using Smartbrush is significantly faster with comparable accuracy.
      CONCLUSIONS: After a period of adjustment to the program, one can comfortably get
      reliable results that, compared with other methods, are not as dependent on the
      user's experience. Smartbrush segmentation is a reliable and fast method of
      segmentation in tumor surgery.

PMID- 25600023
TI  - Epigenomic analysis of the HOX gene loci reveals mechanisms that may control
      canonical expression patterns in AML and normal hematopoietic cells.
AB  - HOX genes are highly expressed in many acute myeloid leukemia (AML) samples, but
      the patterns of expression and associated regulatory mechanisms are not clearly
      understood. We analyzed RNA sequencing data from 179 primary AML samples and
      normal hematopoietic cells to understand the range of expression patterns in
      normal versus leukemic cells. HOX expression in AML was restricted to specific
      genes in the HOXA or HOXB loci, and was highly correlated with recurrent
      cytogenetic abnormalities. However, the majority of samples expressed a canonical
      set of HOXA and HOXB genes that was nearly identical to the expression signature
      of normal hematopoietic stem/progenitor cells. Transcriptional profiles at the
      HOX loci were similar between normal cells and AML samples, and involved
      bidirectional transcription at the center of each gene cluster. Epigenetic
      analysis of a subset of AML samples also identified common regions of chromatin
      accessibility in AML samples and normal CD34(+) cells that displayed differences
      in methylation depending on HOX expression patterns. These data provide an
      integrated epigenetic view of the HOX gene loci in primary AML samples, and
      suggest that HOX expression in most AML samples represents a normal stem cell
      program that is controlled by epigenetic mechanisms at specific regulatory
      elements. 

PMID- 25600026
TI  - Splintless orthognathic surgery: a novel technique using patient-specific
      implants (PSI).
AB  - In the past few years, advances in three-dimensional imaging have conducted to
      breakthrough in the diagnosis, treatment planning and result assessment in
      orthognathic surgery. Hereby error-prone and time-consuming planning steps, like
      model surgery and transfer of the face bow, can be eluded. Numerous positioning
      devices, in order to transfer the three-dimensional treatment plan to the
      intraoperative site, have been described. Nevertheless the use of positioning
      devices and intraoperative splints are failure-prone and time-consuming steps,
      which have to be performed during the operation and during general anesthesia of
      the patient. We describe a novel time-sparing and failsafe technique using
      patient-specific implants (PSI) as positioning guides and concurrently as rigid
      fixation of the maxilla in the planned position. This technique avoids elaborate
      positioning and removal of manufactured positioning devices and allows maxillary
      positioning without the use of occlusal splints. 

PMID- 25600027
TI  - Baicalin can attenuate the inhibitory effects of mifepristone on Wnt pathway
      during peri-implantation period in mice.
AB  - Wnts are considered as important factors in uterus developmental process and
      embryo implantation. Baicalin has been demonstrated to possess tocolytic
      properties. In order to investigate the effect of baicalin on the Wnt signaling
      pathway during the peri-implantation, pregnant Kuming mice were randomly divided
      into four groups: control group, baicalin group administered with 40mg/kg BW of
      baicalin through an intragastric gavage on day 2 to 7 of the pregnancy (Pd2-Pd7),
      mifepristone group treated with 4mg/kg BW of mifepristone, an abortifacient
      agent, via subcutaneous administration on Pd4, and baicalin+mifepristone group
      treated with their combination. The concentrations of the implantation-related
      steroid hormones (progesterone and estradiol) in the blood serum were measured
      with RIA. The gene and protein expression levels of the important molecules of
      the Wnt pathway (Wnt4, LRP6, Dkk1 and beta-catenin) in the endometrium were
      detected with RT-PCR and western blot, respectively. The results showed that
      baicalin decreased (P<0.05) the estradiol levels on Pd4-Pd8 and increased
      (P<0.05) the progesterone levels on Pd3-Pd8. Mifepristone increased (P<0.05) the
      estradiol levels on Pd5-Pd8 and decreased (P<0.05) the progesterone levels on Pd6
      Pd8. Compared with the control group, baicalin increased the gene and protein
      expression levels of Wnt4, LRP6 and beta-catenin (P<0.05) and decreased the gene
      and protein expression levels of Dkk1 (P<0.05) during the middle-to-late stage of
      the experiment in mice uterine tissue. Baicalin alleviated the mifepristone
      induced increase or decrease in the serum levels of progesterone and estradiol,
      and the gene or protein expression levels of Wnt4, LRP6 and beta-catenin. The
      tocolytic properties tocolysis of baicalin may be realized through regulating the
      levels of estrogen/progesterone and the important components of canonical Wnt
      signaling pathway during the embryo implantation process intervened with the
      subcutaneous administration of mifepristone in the mice. 

PMID- 25600028
TI  - [Embolism risk with long bevel needles and plastic tap containers].

PMID- 25600029
TI  - [History and etymology of erysipelas].

PMID- 25600030
TI  - Excess Metabolic and Cardiovascular Risk is not Manifested in all Phenotypes of
      Polycystic Ovary Syndrome: Implications for Diagnosis and Treatment.
AB  - AIM: To assess the potential differences in the metabolic and cardiovascular
      disease (CVD) risk between the distinct phenotypes of the Polycystic Ovary
      Syndrome (PCOS) according to the Rotterdam definition regardless of body mass
      index (BMI). PATIENTS-METHODS: The study included 300 women; 240 women with PCOS,
      according to the Rotterdam criteria and 60 controls without PCOS. All women were
      further subdivided, according to their BMI, into normal-weight and
      overweight/obese and PCOS women were furthermore subdivided to the 4 phenotypes
      of the syndrome. A complete hormonal and metabolic profile as well as the levels
      of high sensitivity C reactive protein (hsCRP) and lipoprotein-associated
      phospholipase A2 (Lp-PLA2) were measured. OUTCOMES: Levels of surrogate markers
      of subclinical atherosclerosis (hsCRP and Lp-PLA2), levels of evaluated CVD risk
      score using risk engines, and several correlations of CVD risk factors. RESULTS:
      hsCRP levels were higher but not significantly so in PCOS women compared with
      controls. In lean PCOS patients, Lp-PLA2 levels were significantly higher,
      compared with lean controls, mainly in the 2 classic phenotypes. Overweight/obese
      patients in all 4 phenotypes had significantly higher Lp-PLA2 levels compared
      with overweight/obese controls. Evaluated CVD risk according to 4 risk engines
      was not different among phenotypes and between PCOS patients and controls. There
      were several correlations of risk factors with metabolic syndrome and non
      alcoholic fatty liver disease requiring appropriate treatment. CONCLUSION: Only 2
      of 4 Rotterdam phenotypes, identical with those of the classic PCOS definition,
      have excess cardiometabolic risk. These need to be treated to prevent CVD events.

PMID- 25600031
TI  - Evaluation of water displacement energetics in protein binding sites with grid
      cell theory.
AB  - Excess free energies, enthalpies and entropies of water in protein binding sites
      were computed via classical simulations and Grid Cell Theory (GCT) analyses for
      three pairs of congeneric ligands in complex with the proteins scytalone
      dehydratase, p38alpha MAP kinase and EGFR kinase respectively. Comparative
      analysis is of interest since the binding modes for each ligand pair differ in
      the displacement of one binding site water molecule, but significant variations
      in relative binding affinities are observed. Protocols that vary in their use of
      restraints on protein and ligand atoms were compared to determine the influence
      of protein-ligand flexibility on computed water structure and energetics, and to
      assess protocols for routine analyses of protein-ligand complexes. The GCT
      derived binding affinities correctly reproduce experimental trends, but the
      magnitude of the predicted changes in binding affinities is exaggerated with
      respect to results from a previous Monte Carlo Free Energy Perturbation study.
      Breakdown of the GCT water free energies into enthalpic and entropic components
      indicates that enthalpy changes dominate the observed variations in energetics.
      In EGFR kinase GCT analyses revealed that replacement of a pyrimidine by a
      cyanopyridine perturbs water energetics up three hydration shells away from the
      ligand. 

PMID- 25600033
TI  - Should otolaryngologists pay more attention to nasal swell bodies?

PMID- 25600032
TI  - Concomitant transatrial valve-in-valve in pulmonal and tricuspid position.
AB  - Transcatheter valve implantation in the pulmonary valve has been established as a
      valuable treatment option for patients with conduit failure in the right
      ventricular outflow tract, most often with the use of the Melody valve.
      Transcatheter valve-in-valve (VIV) implantation in the tricuspid position is
      restricted to single case reports, most often with the implantation of the
      Edwards SAPIEN valve. A 67 years old male with carcionoid syndrome and previously
      implanted bioprosthesis in the pulmonary and tricuspid valve now presented with
      worsening symptoms due to degeneration of both bioprostheses. The risk of new
      open surgery was deemed to high. We report of the first transatrial double VIV
      implantation using the balloon expandable Edwards SAPIEN XT in pulmonary and
      tricuspid position.

PMID- 25600034
TI  - The Role of Metacognition in Pathological Gambling: A Mediation Model.
AB  - Pathological gambling involves multitudinous costs related to financial, legal,
      and public health care aspects, as well as to specific psychological disorders.
      Despite the overall evidence suggesting that comorbid disorders represent a risk
      factor for pathological gambling, there is scant evidence on the appropriate
      treatments for gamblers with such disorders. In this context, metacognitive
      therapy is an interesting approach because it considers psychological disorders
      as a result of the activation of perseverative cognitive processes and
      attentional strategies in response to inner events. Several studies report that
      metacognition is associated with different psychological problems. This study
      investigated the relationship among comorbid disorders, metacognition, and
      pathological gambling. 69 pathological gamblers at the first hospital admission
      and 58 controls drawn from general population (matched for age, gender,
      education) completed a battery of self report instruments: Symptom Checklist-90
      R, Metacognition Questionnaire 30, South Oaks Gambling Scale. Compared to
      controls, pathological gamblers showed higher level of comorbid symptomatology
      and metacognition. Correlation analyses showed that: comorbid symptomatology and
      metacognition were positively and significantly correlated with pathological
      gambling; metacognition was positively and significantly associated with comorbid
      symptomatology. Mediation analysis indicated that dysfunctional metacognitive
      strategies could have an indirect effect on pathological gambling mediated by
      concurrent psychological disorders. These findings provide some implications for
      gambling treatment programs: pathological gamblers should be screened for
      psychiatric disorders, and metacognitive therapy could be considered a correct
      treatment of pathological gamblers. Metacognitive therapy might lead to the
      reduction of the pathological gambling by the diminishing of the concurrent
      psychological disorders. 

PMID- 25600035
TI  - Authors' reply.

PMID- 25600037
TI  - [New SGLT2 inhibitor empagliflozin: modern and safe treatment of diabetes].
AB  - Empagliflozin is agent of new antidiabetic drugs that cause glycosuria blocking
      the glucose reuptake in the proxi-mal tubule. The loss of 50-100 g of glucose /
      24 hours in the urine results in a reduction of fasting glucose, especially post
      prandial glucose, the energy expenditure of 200-400 kcal / day and blood pressure
      lowering. Treatment efficacy does not decrease over time, as it is not dependent
      on its own insulin production. The work evaluates the safety of modern treatment
      with empagliflozin which will soon appear in the portfolio of antidiabetic agents
      in the Czech Republic. The conducted studies with a special focus on
      empagliflozin treatment have shown high efficacy, safety and good tolerability of
      drug. It has been described a higher incidence of genital infections with non
      severe course, especially in women. The drug does not cause hypoglycaemia. In
      combination with sulfonylurea hypoglycaemia may occur. Empagliflozin does not
      cause clinically significant dehydration or hypotension in patients about 60
      years of age, but some caution in empagliflozin treatment should be in elderly
      and fragile patients. The big convenience of empagliflozin is its clinically non
      significant interactions with other drugs and simple dosage of 1 tablet / day
      orally. In conclusion, empagliflozin is highly effective oral antidiabetic agent
      with a potential of wide application in all stages of type 2 diabetes in
      monotherapy or combined with other medication. The treatment is associated with
      weight loss and blood pressure lowering. The drug is effective and safe until
      eGFR 45 ml / s, in lower values the treatment should be discontinued. The
      occurrence of side effects is rare, except increased incidence of genital
      infections especially in women and increased risk of hypoglycaemia when
      empagliflozin is combined with sulfonylurea.

PMID- 25600038
TI  - [Prevention of cardiovascular diseases in clinical practice: is it possible to
      achieve improvement?].
AB  - Prevention through evaluation and treatment of cardiovascular risk factors is an
      efficient approach to reduce the risk of cardiovascular events, however, the
      problem remains that the available treatment options are underused.
      Implementation of cardiovascular disease prevention guidelines into clinical
      practice is therefore important for decreasing the burden of cardiovascular
      disease in general population. However, there are many barriers to this process,
      including questionable relevance of scientific results for clinical practice,
      personal preferences and expertise of the doctors, patient attitudes, lack of
      time, and economical factors. All these factors need to be taken into account for
      any change in the clinical practice to be successful. With respect to
      cardiovascular disease prevention, insufficient screening for risk factors,
      inappropriate risk estimation and hesitation to keep to the guidelines-based
      treatment targets contribute most to inadequate control of risk factors, and this
      has been repeatedly demonstrated to be difficult to improve. In this context, our
      studies demonstrate that the emphasis on systematic application of the principles
      of cardiovascular prevention results in improved control of cardiovascular risk
      factors. Adequate support for transforming the guidelines-based knowledge into
      practicable habit appears therefore important for successful prevention of
      cardiovascular disease in clinical practice and may translate into substantial
      reduction of cardiovascular risk in general population.

PMID- 25600036
TI  - Arterial wave reflection and aortic valve calcification in an elderly community
      based cohort.
AB  - BACKGROUND: Aortic valve calcification (AVC) without stenosis is common in the
      elderly, is associated with cardiovascular morbidity and mortality, and may
      progress to aortic valve stenosis. Arterial stiffness and pulse-wave reflection
      are important components of proximal aortic hemodynamics, but their relationship
      with AVC is not established. METHODS: To investigate the relationship of arterial
      wave reflection and stiffness with AVC, pulse wave analysis and AVC evaluation by
      echocardiography were performed in 867 participants from the Cardiovascular
      Abnormalities and Brain Lesions study. Participants were divided into four
      categories on the basis of the severity and extent of AVC: (1) none or mild focal
      AVC, (2) mild diffuse AVC, (3) moderate to severe focal AVC, and (4) moderate to
      severe diffuse AVC. Central blood pressures and pulse pressure, total arterial
      compliance, augmentation index, and time to wave reflection were assessed using
      applanation tonometry. RESULTS: Indicators of arterial stiffness and wave
      reflection were significantly associated with AVC severity, except for central
      systolic and diastolic pressures and time to reflection. After adjustment for
      pertinent covariates (age, sex, race/ethnicity, and estimated glomerular
      filtration rate), only augmentation pressure (P = .02) and augmentation index (P
      = .002) were associated with the severity of AVC. Multivariate logistic
      regression analysis revealed that augmentation pressure (odds ratio per mm Hg,
      1.14; 95% confidence interval, 1.02-1.27; P = .02) and augmentation index (odds
      ratio per percentage point, 1.07; 95% confidence interval, 1.01-1.13; P = .02)
      were associated with an increased risk for moderate to severe diffuse AVC, even
      when central blood pressure value was included in the same model. CONCLUSIONS:
      Arterial wave reflection is associated with AVC severity, independent of blood
      pressure values. Increased contribution of wave reflection to central blood
      pressure could be involved in the process leading to AVC.

PMID- 25600039
TI  - [Residual cardiovascular risk markers].
AB  - The European definition of biomarker is presented; it is a measurable factor,
      which reflects a physiological or pathological process in human body. There are
      also mentioned transferred meanings of the term marker used in different fields
      of medicine. The importance, categorization and calculation of global
      cardiovascular (CV) risk are explained in patients in primary prevention of CV
      disease (SCORE risk chart). Residual CV risk persists in patients in primary or
      secondary prevention of CV diseases treated according to current guidelines, even
      if their risk factors (blood pressure, LDL-cholesterol, glucose level) have
      achieved the recommended values. This residual risk was done by non-LDL
      dyslipidemia especially, so called atherogenic dyslipidemia (Residual Risk
      Reduction Initiative definition). Investigators of preventive EUROASPIRE studies
      assessed, that 5-year mortality from CV diseases was in a positive association
      with glucose level, smoking and total cholesterol. In our recent analysis, we
      have described among the Czech samples of EUROASPIRE studies I-IV, that BMI and
      prevalence of diabetes increase during the last 16 years very steeply. Patients
      with stable coronary heart diseases in combination with diabetes have had higher
      prevalence of residual risk markers (atherogenic dyslipidemia, atherogenic index
      of plasma described by M. Dobiasova and hypertriglyceridemic waist) than patients
      without diabetes. Except of prescription of statins, ACE inhibitors,
      antiaggregative or anticoagulative drugs was increasing, the residual CV risk was
      not changing during the followed period of 16 years.

PMID- 25600040
TI  - [New aspects of hormone replacement therapy].
AB  - All existing recommendations sign hormone replacement therapy (HRT) as first
      therapy for acute climacteric syndrome. The low dose vaginal therapy is the first
      choice for prevention and therapy of urogenital atrophy and its complications.
      Early start of HRT has neutral or slightly beneficial influence on ischaemic
      heart disease. It is sure that HRT is effective in prevention and therapy of
      postmenopausal osteoporosis. Long term therapy must be individualized on base of
      benefits to risks ratio with differences by type of HRT.

PMID- 25600041
TI  - [News in lipid lowering treatment].
AB  - Options for modification of lipoprotein metabolism and, thus, for reduction of
      atherothrombotic complication have widened over recent years. Apart from the
      development of novel approaches new pharmacological formulations of common lipid
      lowering drugs have been prepared- e.g. statin-containing nanoparticles, fibrate
      nanoparticles with a much higher bioavailability etc. Even the oldest lipid
      lowering agents - resins - have not been forgotten due to its once again
      discovered positive impact of these agents on glucose homeostasis while optimally
      complementing the action of statins. Clinical trials of therapies targeting HDL
      particle metabolism are being in progress despite we have not gathered any
      unambiguous evidence of positive effect of the CETP inhibitors or apoA1 mime-tics
      on the progression of atherosclerosis. Brand new approaches in the treatment of
      dyslipidemia including MTTP and PCSK9 inhibition or therapies utilizing anti
      sense technologies rapidly accumulate evidence from clinical studies. We have
      already learned about their lipid-modifying efficacy particularly in patients
      with familial hypercholesterolemia, however, data from other patients'
      populations can be expected quite soon.

PMID- 25600042
TI  - [Non-pharmacological treatment - results from Podebrady].
AB  - OBJECTIVES: The study was aimed to determine risk factors of atherosclerosis
      after one month lifestyle intervention in overweight/obese children and also FTO
      and MC4R gene variants associated with obesity. DESIGN AND METHODS: 350 non
      diabetic Czech children (age 13.7 +/- 2.1 years, 163 +/- 10.6 cm hight) was
      examined. Before and after 4 weeks of lifestyle intervention (comprising a
      reduction of energy intake), biochemical and anthropometrical measurements were
      performed. RESULTS: The mean weight loss achieved was 6.2 +/- 2.1 kg (P < 0.001).
      Significant associations between BMI decrease and FTO and MC4R variants were
      found. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly
      more body weight in comparison to the non-carriers (P < 0.0009 for BMI and P <
      0.002 for body weight). The differences remain significant after adjustment for
      sex age and baseline values (P = 0.004 for BMI and P = 0.01 for body weight).
      CONCLUSIONS: It is necessary to look for the risk individuals with wrong response
      to the regime intervention. This individuals is necessary early treat with drugs
      to prevention clinically complications.Key words: childhood obesity - components
      of metabolic syndrome - predisposition - response to intervention.

PMID- 25600043
TI  - [Familial hypercholesterolemia - past and present. My experiences and findings in
      our group of patients with familial hypercholesterolemia].
AB  - Currently, the familial hypercholesterolemia (FH) rises the interest. The reason
      is that this genetic disorder is targeted by newly emerged and highly effective
      hypolipidemic agents, PCSK-9 inhibitors, lomitapid and mipomersen. Present paper
      discusses 2 patient study groups, before 50 years and nowadays. Although direct
      statistical analysis is impossible some changes in clinical features of FH might
      be found over the course of the time. In fact, the basic FH characteristic has
      not changed dramatically. Severe isolated hypercholesterolemia with total
      cholesterol 9-10 mmol/l, LDL-cholesterol 7-8 mmol/l and normal values of
      triglycerides dominates in laboratory analysis. Interestingly, the values of
      triglycerides increase and almost reach the pathological range in comparison to
      the values from the period 50 years ago. The values of HDL-cholesterol are
      normal. Manifestation of CHD in male patients over 40 years of age and in female
      patients over 50 years of age is not exceptional (rarely occur cases of
      myocardial infarction in third decade of age). Typical clinical manifestation of
      FH is xanthomatosis. The early detection and aggressive treatment in FH patients
      cause that xanthoma tendinosum, xanthelesma and arcus lipoides are less frequent
      as decades ago. Obesity, diabetes mellitus (DM) and hypertension do not belong to
      typical clinical sign of FH.

PMID- 25600044
TI  - [LDL-apheresis in the treatment familial hypercholesterolemia].
AB  - LDL-apheresis is an extracorporeal elimination technique, which specifically
      removes LDL-cholesterol from the circulation. There are six methods for the
      selective LDL-cholesterol removal these days. The main indications for LDL
      apheresis are the diagnosis of homozygous familial hypercholesterolemia,
      heterozygous familial hypercholesterolemia which is refractory the standard care
      and intolerance of routine care, and also patients with lipoprotein(a) increase
      resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia
      is indication for LDL-apheresis therapy, and the recommendation differs among
      various countries. Despite large randomized trials are missing, there are several
      good quality studies to conclude, that the beneficial cardiovascular effects of
      LDL-apheresis in severe hypercholesterolemia are important and beneficial.

PMID- 25600045
TI  - [Extended options of anticoagulant treatment in thromboembolism].
AB  - Thromboembolic disease (TD) is a relatively common disease with acute risk of
      death and potential long-term consequences in term of postthrombotic syndrome or
      chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic
      procedure; thrombolytic therapy and the introduction cava filter are
      appropriately indicated for individual cases. In past few years, new direct oral
      anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which
      have demonstrated the same efficacy and even higher safety in comparison to
      conventional treatment. In mid 2014, 3 drugs of this group are registered in
      Czech Republic - rivaroxaban (Xarelto(r)), dabigatran (Pradaxa(r)) and apixaban
      (Eliquis(r)). These drugs have comparable efficacy and safety but they differ in
      schedule of dose administration. Rivaroxaban and apixaban can be administered
      immediately after diagnosis of venous thrombosis or hemodynamically stable
      pulmonary embolism. LMWH application has to precede few days the administration
      of dabigatran. Limitation of new drugs is their price. Unavailability of
      antidotes is temporary because current researches continue to find one for
      dabigatran and another for both of xabans. Duration of anticoagulant treatment
      after acute phase depends on the presence of thrombosis risk factors and the
      individual bleeding risk. Minimal duration of anticoagulant therapy is 3 months,
      commonly 6-12 months and in high risk patients it is "long term" treatment. Good
      results of new anticoagulant drugs in trials in term of thromboembolism
      recurrence prevention may change established habits in TD patients with long term
      treatment.

PMID- 25600046
TI  - [What do have arterial and venous disease in common?].
AB  - Venous and arterial disease probably share a number of common risk factors. From
      the pathophysiological point of view a similar triggering mechanism was proposed
      for atherosclerosis and venous disease: subclinical inflammation. Life
      threatening thrombotic events may also go through similar pathways in both
      entities and the culprit is probably dysfunctional endothelial cell in the vessel
      wall. In available clinical and population based studies, however, unequivocal
      data are presented regarding association between arterial and venous diseases and
      their risk factors. In our studies, we found a higher prevalence of lower ankle
      brachial index in women with chronic venous disease of the lower extremities At
      the same time, nevertheless we found no strong evidence of a direct link between
      preclinical atherosclerosis and the occurrence of venous thrombosis in patients
      with thrombophilias; in the latter group, however, we found a link between
      hypertension and thromboembolic events. Arterial and venous disease may thus be
      favorably managed by already well-established and available tools used in
      prevention of atherosclerotic cardiovascular disease. Evidence of a possible
      impact of pharmacotherapy on both arterial and venous disease stems from a large
      clinical study in which treatment with hypolipemic drug, rosuvastatin,
      significantly decreased not only incidence of cardiovascular events but also of
      venous thromboembolic events. Another promising drug for the treatment of both
      arterial and venous disease could be glycosaminoglycan sulodexide.

PMID- 25600047
TI  - [Cardiovascular risk profile in 40-year old men and 50-year old women in the
      Czech Republic: results of a cross-sectional survey].
AB  - BACKGROUND: Cardiovascular (CV) disease belongs to the most important mortality
      causes worldwide. Early identification of risk factors and increased CV risk may
      help decrease of morbidity and mortality. An optimal age for CV risk factors
      screening ages of 40 in males and of 50 in females have been identified. CV risk
      profile of persons in these age categories has been examined by general
      practitioners and recorded for the purposes of this cross-sectional survey.
      METHODS: 1812 persons, males at average age of 40 years and females at average
      age of 50 years, were included into the survey. In each of the examined family
      and personal history including pharmacological were recorded into the study
      protocol as well as abusus and physical activity patterns. Basic anthropometrical
      parameters, e.g. heart rate, blood pressure, body mass index and laboratory
      measures including blood lipids and glycaemia. The participating physicians
      recorded newly identified risk factors CV disease and determined the global CVD
      risk according to the SCORE charts. Percentage of those already treated for any
      of the main CVD risk factors and, among these, also attaining the treatment
      goals. The percentage of patients with a newly identified CV risk factor was
      calculated. We also tested the hypothesis of a relationship between positive
      family history of any of the followed risk factors and its risk in the examined
      probands using Pearson's test. RESULTS: 961 males, average age of 42.9 +/- 4.7
      years, and 851 females , average age of 51.2 +/- 3.6 years, were enrolled into
      the study. 49% of males and 31% of females were overweight and 32% men and 31% of
      women were obese. There were 36% of smokers among men and 22% among women. The
      prevalence of type 2 diabetes was 11% in males and also in females. Arterial
      hypertension was diagnosed in 43% of males and 45% of females while dyslipidemia
      was present in 39% of males and 41% of females. Pharmacological treatment of any
      of the above mentioned diseases was used in 48% of the probands, however, only 7%
      of them attained treatment goals of blood pressure, LDL-cholesterol and
      glycaemia. Type 2 diabetes was newly identified in 3% of both males and females,
      arterial hypertension in 8% of males and 5% of females and dyslipidemia was newly
      detected in 20% of probands of both genders. Non-pharmacological treatment was
      recommended to 62% of male and to 65% of female participants, respectively.
      Pharmacological treatment was initiated in 53% of males and 51% of females. In
      both genders this was mostly antihypertensive treatment with ACE inhibitors (29%
      of males and 24% of females) and lipid lowering therapy with a statin (29% of
      males, 27% females). The analysis of relationship between the positive family
      history of any of the followed diseases and their presence in the probands
      examined revealed significant increases of the risk for arterial hypertension,
      type 2 diabetes mellitus and dyslipidemia. CONCLUSION: The survey following CV
      risk profile in a cohort of 40 years old men and 50 years old women showed high
      prevalence of CV risk factors in these age categories in the Czech probands. The
      high frequency of modifiable risk factors and the need to initiate
      pharmacological treatment in more than one half of the examined population
      documents the need of early detection of risk. Genetic determination of
      individual major risk factors for CVD mirrored in the positive family history
      represents an important component of the global cardiovascular risk and must be
      actively detected and taken into account for the risk stratification.

PMID- 25600048
TI  - [Adherence of type 2 diabetes patients on insulin analogues application: missed
      dose, time imprecision and dose reduction. The results of GAPP2TM(Global
      Attitudes of Physicians and Patient) survey in the Czech Republic].
AB  - OBJECTIVE: Irregular insulin dose is one of the main problems associated with
      insulin therapy in patients with type 2 diabetes; its extent is not known
      precisely. The aim of survey conducted in the Czech Republic in the international
      project GAPP2 - Global Attitudes of Patients and Physicians was to determine the
      incidence and the impact of irregular use of basal insulin analogues in patients
      with type 2 diabetes, to point out the reasons for these irregularities and to
      focus on how physicians discuss irregular application of insulin with patients.
      METHODS: The project GAPP2 is an international cross-sectional study performed on
      line via the Internet using a questionnaire filled by diabetic patients treated
      with insulin analogues and physicians who treat these patients. The survey was
      conducted in two steps in 17 countries; the first step included 6 countries and
      was completed in the beginning of 2012, the second step involved 11 other
      countries including the Czech Republic with termination in 2014. The survey was
      designed to obtain the views of patients and physicians on certain aspects of
      insulin treatment and persistent issues in this field in the real daily practice.
      Special focus was on the incidence and management of hypoglycaemia as well as on
      irregularities of insulin application. In the part dedicated to adherence to
      basal insulin application were observed three types of irregular insulin therapy:
      missed dose, time imprecision of dose (+/- 2 hours vs. the prescribed time) and
      dose reduction in all cases in the past 30 days before completing the
      questionnaire. In addition, it was investigated the attitude and relation of
      patients to these issues. RESULTS: The results have shown that irregular insulin
      dose in the Czech Republic is less frequent than in other countries involved in
      the GAPP2 research. Nevertheless, approximately one fifth of diabetic patients
      using insulin analogues in basal-bolus or only basal therapy regimen is related
      to this problem. The last irregular insulin application was due to missed dose in
      13% of cases, time imprecision in 23% and reduction of dose in 61% of cases. The
      most commonly reported reason was risk reduction of hypoglycaemia and the
      recommendations of health professionals. Fear of missed dose is present in 40%
      Czech patients and 35% would feel guilty if their insulin dose is missed (up to
      47% in patients with intensified insulin regimen). Only 60% patients are aware of
      negative impact on their long-term health after missed dose of basal insulin.
      Questioned doctors have suspected that the patients report lower number of missed
      doses during regular medical check because one third of patients doesn't admit
      missed dose. However, this fact conceded only 11% of patients on basal insulin
      and 15% of patients on intensified insulin therapy. Quarter of prescribing
      doctors admit that they usually don't discuss with patients irregularities in
      basal insulin treatment. CONCLUSION: Although, type 2 diabetes patients in the
      Czech Republic follow prescribed basal insulin therapy scheme more often than
      patients in other countries participating in the survey GAPP2 , missed dose, time
      imprecision and reduction of dose is quite common and it deserves more attention
      from medical side during regular medical check together with appropriate
      education of patients.

PMID- 25600049
TI  - Serum folate, vitamin B12 and cognitive impairment in Chilean older adults.
AB  - OBJECTIVE: To analyse the relationship between serum folate (SF), vitamin B12 and
      impaired cognitive function in the Chilean elderly. DESIGN: We analysed the
      relationships between impaired cognitive function and age, SF (ug/l) and vitamin
      B12 (pg/ml) with Student's t test, as well as between impaired cognitive function
      and gender, educational level, residence area, diabetes and hypertension with the
      chi 2 test. Multiple logistic regressions with interactions were estimated to
      assess the impact of SF on impaired cognitive function according to these
      methods. SETTING: Chile. SUBJECTS: Older adults (>65 years, n 1051), drawn from
      representative households of a national prevalence study, assessed using the
      Modified Mini Mental Status Examination (MMMSE). Individuals with altered MMMSE
      scores (<=13 points) were sequentially assessed using the Pfeffer Functional
      Activities Questionnaire (PFAQ). RESULTS: Multivariate models using the MMMSE
      demonstrated an increased risk of impaired cognitive function for seniors who had
      hypertension, diabetes and higher vitamin B12 levels. SF and its square (SF2)
      were statistically significant, indicating that this predictor of impaired
      cognitive function displays a U-shaped distribution. The interaction between SF
      and vitamin B12 was not statistically significant. Models using the MMMSE plus
      PFAQ suggested that urban residence decreased the risk of impaired cognitive
      function, whereas male gender, older age, vitamin B12 levels and hypertension
      increased this risk. The variables SF and SF2 and the SF * vitamin B12
      interaction were statistically significant (P<0.05). The risk of impaired
      cognitive function depended on different combinations of SF and vitamin B12
      levels. When SF was low, a one-unit increase in SF (1 ug/l) diminished the risk.
      When SF was elevated, a further increase in SF raised the risk, especially at low
      vitamin B12 levels. CONCLUSIONS: The relationship between folate, vitamin B12 and
      impaired cognitive function warrants further study.

PMID- 25600052
TI  - On the decomposition of life expectancy and limits to life.
AB  - Life expectancy is a measure of how long people are expected to live and is
      widely used as a measure of human development. Variations in the measure reflect
      not only the process of ageing but also the impacts of such events as epidemics,
      wars, and economic recessions. Since 1950, the influence of these events in the
      most developed countries has waned and life expectancy continues to lengthen
      unabated. As a result, it has become more difficult to forecast long-run trends
      accurately, or identify possible upper limits. We present new methods for
      comparing past improvements in life expectancy and also future prospects, using
      data from five developed, low-mortality countries. We consider life expectancy in
      10-year age intervals rather than over the remaining lifetime, and show how
      natural limits to life expectancy can be used to extrapolate trends. We discuss
      the implications and compare our approach with other commonly used methods.

PMID- 25600050
TI  - Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients
      with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia.
AB  - Background We determined the safety, pharmacokinetics, pharmacodynamics, and
      antitumour activity of abexinostat in B-cell lymphoma or chronic lymphocytic
      leukaemia. Patients and methods Thirty-five patients received oral abexinostat
      30, 45, or 60 mg/m(2) bid in a 3 + 3 design in three 21-day schedules: 14 days on
      treatment in schedule 1 (D1-14); 10 days in schedule 2 (D1-5 and D8-12); and 12
      days in schedule 3 (D1-4, D8-11, and D15-18). Safety, tumour response, plasma
      concentration, and histone H3 acetylation were measured. Results Two dose
      limiting toxicities occurred in each schedule (one grade 3 febrile neutropenia;
      five grade 4 thrombocytopenia) at 60 mg/m(2) bid (maximal tolerated dose). The
      recommended dose was 45 mg/m(2) bid; schedule 1 was considered optimal. Non
      haematological drug-related toxicities included grade 1 or 2 diarrhoea (43%),
      nausea (23%), and vomiting (11%); haematological toxicities included
      thrombocytopenia (31% grade 3, and 26% grade 4), which remained manageable and
      reversible on withdrawal. Of 29 evaluable patients, there were 2 complete and 6
      partial responses; median duration of response was 14.6 months (range 3-16.5
      months) (1 cycle is equivalent to 0.75 months). There was no evidence for
      nonlinear pharmacokinetics. There was a correlation between dose and histone
      acetylation. Conclusion Abexinostat has manageable toxicity and induced some
      durable complete and partial responses in B-cell lymphoma or chronic lymphocytic
      leukaemia. Our results suggest most favourable responses in patients with
      follicular lymphoma, though further research would be needed to confirm this
      finding.

PMID- 25600051
TI  - Surgical approach for nodular neck lesions mimicking primitive thyroid neoplasms
      Report of three cases.
AB  - AIM: The finding of a neck nodular lesion provides strong suspicion of primary
      thyroid malignancy. Direct extension into the thyroid parenchyma of carcinomas
      arising from pharynx, larynx, trachea or esophagus, nervous structures has been
      also observed in the minority of cases. The intent of our study is to present and
      discuss rare conditions presenting asymptomatic neck masses, with particular
      emphasis on pre-operative characteristics and diagnostic criteria. MATERIAL OF
      STUDY: In our retrospective analysis, we present three cases of nodular neck
      lesions that have mimicked primitive thyroid pathologies at the first diagnosis.
      RESULTS: A 53-mm nodular mass in the right thyroid lobe was observed in one
      patient. The definitive diagnosis was Castleman's disease. The second case
      presented a 20-mm hypoechoic lesion in the contest of a multinodular goiter. The
      pre-operative suspect was thyroid carcinoma with lymphnode metastases but the
      definitive histology documented an 'ancient schwannoma'. A further patient
      presented bilateral supra-clavear and cervical lymphnodes in a multinodular
      goiter, initially interpreted as thyroid carcinoma with loco-regional spread.
      After a total thyroidectomy and cervical lymphadenectomy, the definitive
      histology documented foci of poorly differentiated carcinoma in cervical
      lymphnodes and a multinodular goiter without atypical cellularity. The patient is
      considered to have an occult tumor, probably arising from the breast, and she was
      scheduled in an oncological program. CONCLUSIONS: Nodular neck lesions are
      frequently misdiagnosed as primitive thyroid nodules in the common clinical
      practice. In these rare conditions, surgical exploration is advocated to reach
      the definitive diagnosis, to indicate the most appropriate treatment and to avoid
      unnecessary thyroidectomy. KEY WORDS: Ancient Schwannoma, Castleman's disease,
      Nodular neck lesion, Thyroid nodule.

PMID- 25600053
TI  - The effect of exogenous surfactant on alveolar interdependence.
AB  - To investigate the nature of alveolar mechanical interdependence, we purposefully
      disturbed the equilibrium condition by administering exogenous surfactant in
      physiological non-surfactant deprived conditions. Changes in alveolar morphology
      induced by intra-tracheal delivery of CUROSURF were evaluated after opening a
      pleural window allowing in-vivo microscopic imaging of sub-pleural alveoli in 6
      male anesthetized, tracheotomized and mechanically ventilated rabbits. Surfactant
      instillation increased the surface area of alveoli smaller than 20,000 MUm(2) up
      to ~ 50% at 15 min after instillation, reflecting a lowering of surface tension
      due to local surfactant enrichment. Conversely, for alveoli greater than 20,000
      MUm(2), surface area decreased by ~ 5%. Opposite changes in alveolar surface are
      interpreted as reflecting a new inter-alveolar mechanical equilibrium modified by
      local surfactant distribution and by a decrease in lung distending pressure. We
      propose that smaller alveoli, representing the majority of alveolar population,
      might mostly contribute to improve the oxygenation index following surfactant
      replacement therapy in case of surfactant deficiency.

PMID- 25600054
TI  - Determination of tapentadol and tapentadol-O-glucuronide in human serum samples
      by UPLC-MS/MS.
AB  - Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action,
      MOR agonism and noradrenaline (NA) reuptake inhibition in a single molecule. It
      is the first member of a new therapeutic class, MOR-NRI. A high throughput liquid
      chromatography-tandem mass spectrometric (LC-MS/MS) assay was developed and
      validated for the quantitative analysis of tapentadol and its O-glucuronide
      metabolite in human serum. Simultaneous quantification was deemed to be
      challenging because of the large difference in concentrations between tapentadol
      and its O-glucuronide metabolite in clinical samples. Therefore, a method was
      established using a common processed sample, but with different injection volumes
      and chromatographic conditions for each analyte. Tapentadol and tapentadol-O
      glucuronide were determined by protein precipitation of 0.100ml of the samples
      with acetonitrile. The internal standards used are D6-tapentadol and D6
      tapentadol-O-glucuronide. The validated concentration range was 0.200-200 ng/ml
      (tapentadol) and 10.0-10,000 ng/ml (tapentadol-O-glucuronide). Chromatographic
      separation was achieved by gradient elution on a Waters Acquity UPLC BEH C18 (1.7
      MUm, 2.1 * 50 mm) column, with mobile phase consisting of 0.01 M ammonium formate
      (adjusted to pH 4 using formic acid) (A) and methanol (B). A separate injection
      was done for measurement of each analyte, with a different gradient and run time.
      The analytes were detected by using an electrospray ion source on a triple
      quadrupole mass spectrometer operating in positive ionization mode. The run time
      was 1.6 min for tapentadol and 1.5 min for tapentadol-O-glucuronide. The high
      sensitivity and acceptable performance of the assay allowed its application to
      the analysis of serum samples in clinical trials. The validated method was used
      for analysis of tapentadol in over 17,000 samples.

PMID- 25600055
TI  - Establishment of a three-step purification scheme for a recombinant protein
      rG17PE38 and its characteristics identification.
AB  - A protein with high purity has become an essential pre-requisite for
      investigating its bioactivity, molecular structure and characteristics.
      Therefore, the development of technologies for efficient purification of protein
      is urgently necessary. The objective of this study was to establish a
      purification protocol for a recombinant protein rG17PE38. Different forms of
      chromatography such as hydrophobic interaction and ion exchange chromatography
      were chosen as the core purification steps. The performance of each technique was
      optimized to meet the requirements and the purification steps were arranged in a
      logical way of facilitating to operate in next step. In addition, some
      characteristics of the protein such as stability, bioactivity and cellular
      location were determined. Finally, whether the protein could induce cell
      apoptosis was also explored. The results showed the protein purified via the
      suggested three-step purification scheme could obtain a purity of 95%, and its
      bioactivity in the form of IC50 was 17.6 ng/mL, furthermore it could keep stable
      at 4  degrees C for at least 10 days. The protein could bind on its target cell
      membrane specifically, and inducing cell apoptosis was demonstrated to be one of
      the cytotoxicity mechanisms of the protein. Results obtained in our study may
      provide useful information on strategies of protein purification and lay a
      substantial foundation for the followed animal or clinical experiments on
      rG17PE38.

PMID- 25600056
TI  - QSAR prediction of HIV-1 protease inhibitory activities using docking derived
      molecular descriptors.
AB  - In this study, application of a new hybrid docking-quantitative structure
      activity relationship (QSAR) methodology to model and predict the HIV-1 protease
      inhibitory activities of a series of newly synthesized chemicals is reported.
      This hybrid docking-QSAR approach can provide valuable information about the most
      important chemical and structural features of the ligands that affect their
      inhibitory activities. Docking studies were used to find the actual conformations
      of chemicals in active site of HIV-1 protease. Then the molecular descriptors
      were calculated from these conformations. Multiple linear regression (MLR) and
      least square support vector machine (LS-SVM) were used as QSAR models,
      respectively. The obtained results reveal that statistical parameters of the LS
      SVM model are better than the MLR model, which indicate that there are some non
      linear relations between selected molecular descriptors and anti-HIV activities
      of interested chemicals. The correlation coefficient (R), root mean square error
      (RMSE) and average absolute error (AAE) for LS-SVM are: R=0.988, RMSE=0.207 and
      AAE=0.145 for the training set, and R=0.965, RMSE=0.403 and AAE=0.338 for the
      test set. Leave one out cross validation test was used for assessment of the
      predictive power and validity of models which led to cross-validation correlation
      coefficient QUOTE of 0.864 and 0.850 and standardized predicted relative error
      sum of squares (SPRESS) of 0.553 and 0.581 for LS-SVM and MLR models,
      respectively. 

PMID- 25600057
TI  - A review of technological and clinical aspects of robot-aided rehabilitation of
      upper-extremity after stroke.
AB  - Cerebrovascular accident (CVA) or stroke is one of the leading causes of
      disability and loss of motor function. Millions of people around the world are
      effected by it each year. Stroke results in disabled arm function. Restoration of
      arm function is essential to regaining activities of daily living (ADL). Along
      with traditional rehabilitation methods, robot-aided therapy has emerged in
      recent years. Robot-aided rehabilitation is more intensive, of longer duration
      and more repetitive. Using robots, repetitive dull exercises can turn into a more
      challenging and motivating tasks such as games. Besides, robots can provide a
      quantitative measure of the rehabilitation progress. This article overviews the
      terms used in robot-aided upper-limb rehabilitation. It continues by
      investigating the requirements for rehabilitation robots. Then the most
      outstanding works in robot-aided upper-limb rehabilitation and their control
      schemes have been investigated. The clinical outcomes of the built robots are
      also given that demonstrates the usability of these robots in real-life
      applications and their acceptance. This article summarizes a review done along
      with a research on the design, simulation and control of a robot for use in upper
      limb rehabilitation after stroke. Implications for Rehabilitation Reviewing
      common terms in rehabilitation of upper limb using robots Reviewing
      rehabilitation robots built up to date Reviewing clinical outcomes of the
      mentioned rehabilitation robots. 

PMID- 25600058
TI  - Non-destructive functionalisation for atomic layer deposition of metal oxides on
      carbon nanotubes: effect of linking agents and defects.
AB  - The hybridisation of metal oxides and nanocarbons has created a promising new
      class of functional materials for environmental and sustainable energy
      applications. The performance of such hybrids can be further improved by
      rationally designing interfaces and morphologies. Atomic layer deposition (ALD)
      is among the most powerful techniques for the controlled deposition of inorganic
      compounds, due to its ability to form conformal coatings on porous substrates at
      low temperatures with high surface sensitivity and atomic control of film
      thickness. The hydrophobic nature of the nanocarbon surface has so far limited
      the applicability of ALD on CNTs. Herein we investigate the role of structural
      defects in CNTs, both intrinsic and induced by acid treatment, on coverage,
      uniformity and crystallinity of ZnO coatings. Furthermore, we demonstrate the
      potential of small aromatic molecules, including benzyl alcohol (BA), naphthalene
      carboxylic acid (NA) and pyrene carboxylic acid (PCA), as active nucleation sites
      and linking agents. Importantly, only PCA exhibits sufficiently strong
      interactions with the pristine CNT surface to withstand desorption under reaction
      conditions. Thus, PCA enables a versatile and non-destructive alternative route
      for the deposition of highly uniform metal oxide coatings onto pristine CNTs via
      ALD over a wide temperature range and without the typical surface corrosion
      induced by covalent functionalisation. Importantly, preliminary tests
      demonstrated that the improved morphology obtained with PCA has indeed
      considerably increased the hybrid's photocatalytic activity towards hydrogen
      evolution via sacrificial water splitting. The concept demonstrated in this work
      is transferable to a wide range of other inorganic compounds including metal
      oxides, metal (oxy)nitrides and metal chalcogenides on a variety of nanocarbons. 

PMID- 25600059
TI  - Alterations in drug disposition in older adults.
AB  - INTRODUCTION: The worldwide population is aging, and several age-associated
      physiological and pathophysiological changes can affect drug disposition. This is
      particularly important in view of the extensive medication prescribing and
      exposure in older adults. AREAS COVERED: Using a framework of the four primary
      pharmacokinetic processes (Absorption, Distribution, Metabolism and Elimination),
      this review discusses the current evidence of the pharmacokinetic changes that
      occur with aging, particularly 'healthy aging,' focusing on developments in this
      field over the last 10 years. EXPERT OPINION: A substantial amount of work has
      been conducted to address whether advancing age significantly affects drug
      disposition in humans. Despite significant advances in the field, particularly
      regarding drug metabolism and elimination, a number of issues remain unsolved. In
      particular, lack of inclusion of older adults with multimorbidity and those aged
      > 80 and minimal evidence in relation to new drugs limits the applicability of
      findings to current clinical practice.

PMID- 25600060
TI  - In Vitro and In Vivo Radiosensitizing Effect of Valproic Acid on Fractionated
      Irradiation.
AB  - PURPOSE: This study was conducted in order to validate the radiosensitization
      effect of valproic acid, a biologically available histone deacetylase inhibitor,
      for fractionated radiation. MATERIALS AND METHODS: Radiosensitization effect of
      valproic acid was tested for the A549 cell line and U87MG cell line in vitro.
      Fractionated irradiation of 12 Gy in four fractions was administered on D2-5 with
      valproic acid, 150 mg/Kg, ip, bid for six consecutive days (D1-6) to A549 and
      U87MG tumors implanted in BALB/c-nude mice. A growth delay curve was formulated.
      RESULTS: Radiosensitization effect of valproic acid was found for both cell
      lines; A549 at 1.5 mM and 3.0 mM concentration and U87MG at 3.0 mM concentration.
      In growth delay analysis, a statistically significant radiosensitization effect
      was observed for both tumors (p < 0.001 for both tumors). Difference for change
      in slope for control and valproic acid versus radiotherapy and radiotherapy plus
      valproic acid showed borderline significance for the U87MG cell line (p=0.065),
      indicating beyond additive effect, whereas this difference was statistically
      insignificant for A549 tumor (p=0.951), indicating additive effect. CONCLUSION:
      Results of this study indicate that a radiosensitizing effect for fractionated
      radiotherapy of valproic acid for A549 and U87MG tumors in vivo is evident and
      that it may be more than additive for U87MG tumors. Further exploitation of
      histone deacetylase inhibitors in clinical trials is warranted.

PMID- 25600061
TI  - Tumor Growth Suppression and Enhanced Radioresponse by an Exogenous Epidermal
      Growth Factor in Mouse Xenograft Models with A431 Cells.
AB  - PURPOSE: The purpose of this study was to evaluate whether an exogenous epidermal
      growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo.
      MATERIALS AND METHODS: BALB/c-nu mice that were inoculated with A431 (human
      squamous cell carcinoma) cells in the right hind legs were divided into five
      groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV
      (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered
      intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six
      fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung,
      and kidney tissues were investigated. Additionally, tumors were subjected to
      immunohistochemistry staining with caspase-3. RESULTS: EGF for 6 days decreased
      tumor volume, but it approached the level of the control group at the end of
      follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V
      while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF
      for 20 days decreased tumor volume until the end of the observation period (p <
      0.001). Immunohistochemistry revealed that mice in group V showed stronger
      intensity than those in group IV. There were no abnormal histological findings
      upon H&E staining of the normal organs. CONCLUSION: EGF-induced anti-tumor effect
      was ascertained in the xenograft mouse models with A431 cells. Concomitant use of
      EGF has the potential role as a radiosensitizer in the design of fractionated
      irradiation.

PMID- 25600064
TI  - Prenatal imaging and immunohistochemical analysis of congenital peribronchial
      myofibroblastic tumor.

PMID- 25600063
TI  - Optimal site for ultrasound-guided venous catheterisation in paediatric patients:
      an observational study to investigate predictors for catheterisation success and
      a randomised controlled study to determine the most successful site.
AB  - INTRODUCTION: Venous catheterisation in paediatric patients can be technically
      challenging. We examined factors affecting catheterisation of invisible and
      impalpable peripheral veins in children and evaluated the best site for
      ultrasound-guided catheterisation. METHODS: Systolic pressure, age, sex, and
      American Society of Anaesthesiologists (ASA) physical status were determined in
      96 children weighing less than 20 kg. Vein diameter and subcutaneous depth were
      measured with ultrasound. Logistic regression was used to evaluate the
      contribution of these factors to cannulation success with (n = 65) or without (n
      = 31) ultrasound guidance. Thereafter, we randomly assigned 196 patients for
      venous catheter insertion in the dorsal veins of the hand, the cephalic vein in
      the forearm, or the great saphenous vein. Success rates and vein diameters were
      evaluated by using Dunn tests; insertion time was evaluated by using Kaplan-Meier
      cumulative incidence analysis. RESULTS: Independent predictors of catheterisation
      were ultrasound guidance (odds ratio (OR) = 7.3, 95% confidence interval (CI) 2.0
      to 26.0, P = 0.002), vein diameter (OR = 1.5 per 0.1 mm increase in diameter, 95%
      CI 1.1 to 2.0, P = 0.007), and ASA physical status (OR = 0.4 per status 1
      increase, 95% CI 0.2 to 0.9, P = 0.03). Cephalic veins were significantly larger
      (cephalic diameter 1.8 mm, P = 0.001 versus saphenous 1.5 mm, P <0.001 versus
      dorsal 1.5 mm). Catheterisation success rates were significantly better at the
      cephalic vein than either the dorsal hand or saphenous vein (cephalic 95%, 95% CI
      89% to 100%, P <0.001 versus dorsal 69%, 95% CI 56% to 82%, P = 0.03 versus
      saphenous 75%, 95% CI 64% to 86%). CONCLUSIONS: The cephalic vein in the proximal
      forearm appears to be the most appropriate initial site for ultrasound-guided
      catheterisation in invisible and impalpable veins of paediatric patients. TRIAL
      REGISTRY NUMBER: UMIN Clinical Trials Registry as UMIN000010961. Registered on 14
      June 2013.

PMID- 25600065
TI  - Adult-onset vanishing white matter disease with novel missense mutations in a
      subunit of translational regulator, EIF2B4.

PMID- 25600066
TI  - Impulsivity in borderline personality disorder.
AB  - BACKGROUND: Impulsivity is a core feature of borderline personality disorder
      (BPD) and is most frequently measured using self-rating scales. There is a need
      to find objective, valid and reliable measures of impulsivity. This study aimed
      to examine performance of participants with BPD compared with healthy controls on
      delay and probabilistic discounting tasks and the stop-signal task (SST), which
      are objective measures of choice and motor impulsivity, respectively. METHOD: A
      total of 20 participants with BPD and 21 healthy control participants completed
      delay and probabilistic discounting tasks and the SST. They also completed the
      Barratt Impulsiveness Scale (BIS), a self-rating measure of impulsivity. RESULTS:
      Participants with BPD showed significantly greater delay discounting than
      controls, manifest as a greater tendency to accept the immediately available
      lesser reward rather than waiting longer for a greater reward. Similarly they
      showed significantly greater discounting of rewards by the probability of payout,
      which correlated with past childhood trauma. Participants with BPD were found to
      choose the more certain and/or immediate rewards, irrespective of the value. On
      the SST the BPD and control groups did not differ significantly, demonstrating no
      difference in motor impulsivity. There was no significant difference between
      groups on self-reported impulsivity as measured by the BIS. CONCLUSIONS: Measures
      of impulsivity show that while motor impulsivity was not significantly different
      in participants with BPD compared with controls, choice or reward-related
      impulsivity was significantly affected in those with BPD. This suggests that
      choice impulsivity but not motor impulsivity is a core feature of BPD.

PMID- 25600067
TI  - T-Brain-1--A Potential Master Regulator in Autism Spectrum Disorders.
AB  - T-Brain-1 (TBR1), a causative gene in autism spectrum disorders (ASDs), encodes a
      brain-specific T-box transcription factor. It is therefore possible that TBR1
      controls the expression of other autism risk factors. The downstream genes of
      TBR1 have been identified using microarray and promoter analyses. In this study,
      we annotated individual genes downstream of TBR1 and investigated any
      associations with ASDs through extensive literature searches. Of 124 TBR1 target
      genes, 23 were reported to be associated with ASDs. In addition, one gene,
      Kiaa0319, is a known causative gene for dyslexia, a disorder frequently
      associated with autism. A change in expression level in 10 of these 24 genes has
      been previously confirmed. We further validated the alteration of RNA expression
      levels of Kiaa0319, Baiap2, and Gad1 in Tbr1 deficient mice. Among these 24
      genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found,
      suggesting that TBR1 controls a transcriptional cascade relevant to autism
      pathogenesis. A further five of the 24 genes (Cd44, Cdh8, Cntn6, Gpc6, and Ntng1)
      encode membrane proteins that regulate cell adhesion and axonal outgrowth. These
      genes likely contribute to the role of TBR1 in regulation of neuronal migration
      and axonal extension. Besides, decreases in Grin2b expression and increases in
      Gad1 expression imply that neuronal activity may be aberrant in Tbr1 deficient
      mice. These analyses provide direction for future experiments to reveal the
      pathogenic mechanism of autism.

PMID- 25600068
TI  - Telocytes transfer extracellular vesicles loaded with microRNAs to stem cells.
AB  - Telocytes (TCs) are cells ubiquitously distributed in the body and characterized
      by very long and thin prolongations named telopodes (Tps). Cardiac TCs are the
      best characterized TCs for the moment. Tps release extracellular vesicles (EVs)
      in vivo and in vitro suggesting that TCs regulate the activity of other cells by
      vesicular paracrine signals. TCs have been found within the stem cell niche of
      several organs. Electron microscopy or electron tomography has shown that Tps are
      located in close vicinity of stem cells (SC). Since stem cell regulation by niche
      components involves paracrine signalling, we have investigated if TCs could be
      part of this mechanism. Using fluorescent labelling of cells and EVs with calcein
      and Cy5-miR-21 oligos, we provide evidence that TCs can modulate SC through EVs
      loaded with microRNAs. TCs deliver microRNA to cardiac stem cells (CSCs), as well
      as to other types of SCs (e.g. hematopoietic SC) indicating that this mechanism
      is not restricted to cardiac tissue. We also found that CSCs deliver microRNA
      loaded EVs to TCs, suggesting that there is a continuous, post-transcriptional
      regulatory signal back and forth between TCs and SC. In conclusion, our data
      reveal the existence of a reciprocal (bidirectional) epigenetic signalling
      between TCs and SC. 

PMID- 25600069
TI  - Electron tunneling rates in respiratory complex I are tuned for efficient energy
      conversion.
AB  - Respiratory complex I converts the free energy of ubiquinone reduction by NADH
      into a proton motive force, a redox reaction catalyzed by flavin
      mononucleotide(FMN) and a chain of seven iron-sulfur centers. Electron transfer
      rates between the centers were determined by ultrafast freeze-quenching and
      analysis by EPR and UV/Vis spectroscopy. The complex rapidly oxidizes three NADH
      molecules. The electron-tunneling rate between the most distant centers in the
      middle of the chain depends on the redox state of center N2 at the end of the
      chain, and is sixfold slower when N2 is reduced. The conformational changes that
      accompany reduction of N2 decrease the electronic coupling of the longest
      electron-tunneling step. The chain of iron-sulfur centers is not just a simple
      electron-conducting wire; it regulates the electron-tunneling rate synchronizing
      it with conformation-mediated proton pumping, enabling efficient energy
      conversion. Synchronization of rates is a principle means of enhancing the
      specificity of enzymatic reactions. 

PMID- 25600070
TI  - Osteoblast-Specific gamma-Glutamyl Carboxylase-Deficient Mice Display Enhanced
      Bone Formation With Aberrant Mineralization.
AB  - Vitamin K is a fat-soluble vitamin that is necessary for blood coagulation. In
      addition, it has bone-protective effects. Vitamin K functions as a cofactor of
      gamma-glutamyl carboxylase (GGCX), which activates its substrates by
      carboxylation. These substrates are found throughout the body and examples
      include hepatic blood coagulation factors. Furthermore, vitamin K functions as a
      ligand of the nuclear receptor known as steroid and xenobiotic receptor (SXR) and
      its murine ortholog, pregnane X receptor (PXR). We have previously reported on
      the bone-protective role of SXR/PXR signaling by demonstrating that systemic Pxr
      knockout mice displayed osteopenia. Because systemic Ggcx-knockout mice die
      shortly after birth from severe hemorrhage, the GGCX-mediated effect of vitamin K
      on bone metabolism has been difficult to evaluate. In this work, we utilized Ggcx
      floxed mice to generate osteoblast-specific GGCX-deficient
      (Ggcx(Deltaobl/Deltaobl)) mice by crossing them with Col1-Cre mice. The bone
      mineral density (BMD) of Ggcx(Deltaobl/Deltaobl) mice was significantly higher
      than that of control Col1-Cre (Ggcx(+/+)) mice. Histomorphometrical analysis of
      trabecular bones in the proximal tibia showed increased osteoid volume and a
      higher rate of bone formation in Ggcx(Deltaobl/Deltaobl) mice.
      Histomorphometrical analysis of cortical bones revealed a thicker cortical width
      and a higher rate of bone formation in Ggcx(Deltaobl/Deltaobl) mice. Electron
      microscopic examination revealed disassembly of mineralized nodules and aberrant
      calcification of collagen fibers in Ggcx(Deltaobl/Deltaobl) mice. The mechanical
      properties of bones from Ggcx(Deltaobl/Deltaobl) mice tended to be stronger than
      those from control Ggcx(+/+) mice. These results suggest that GGCX in osteoblasts
      functions to prevent abnormal mineralization in bone formation, although this
      function may not be a prerequisite for the bone-protective effect of vitamin K.

PMID- 25600071
TI  - Most countries will fail to meet targets on non-communicable diseases, says WHO.

PMID- 25600072
TI  - Correction: Alpha-enolase as a potential cancer prognostic marker promotes cell
      growth, migration, and invasion in glioma.

PMID- 25600073
TI  - Synthesis and Preliminary Antiviral Activities of Piperidine-substituted Purines
      against HIV and Influenza A/H1N1 Infections.
AB  - We have developed a series of N(2) -(1-(substituted-aryl)piperidin-4-yl)-N(6) 
      mesityl-9H-purine-2,6-diamine derivatives as potent antiviral agents. Preliminary
      biological evaluation indicated that nearly half of them possessed remarkable HIV
      inhibitory potencies in cellular assays. In particular, FZJ13 appeared to be the
      most notable one, which displayed anti-HIV-1 activity compared to 3TC. Moreover,
      an unexpected finding was that FZJ05 displayed significant potency against
      influenza A/H1N1 (strain A/PR/8/34) in Madin-Darby canine kidney cells with EC50
      values much lower than those of ribavirin, amantadine, and rimantadine. The
      results suggest that these novel purine derivatives have the potential to be
      further developed as new therapeutic agents against HIV-1 or influenza virus. 

PMID- 25600074
TI  - Inhibiting plant microRNA activity: molecular SPONGEs, target MIMICs and STTMs
      all display variable efficacies against target microRNAs.
AB  - Elucidation of microRNA (miRNA) function through a loss-of-function approach has
      proven difficult due to extensive genetic redundancy among most plant and animal
      miRNA families. Consequently, miRNA decoy technologies such as target MIMICs
      (MIMs) and short tandem target MIMICs (STTMs) in plants or molecular SPONGEs
      (SPs) in animals have been developed to generate loss-of-function phenotypes by
      perturbing endogenous miRNA activity. To test whether SPs can inhibit plant miRNA
      activity, synthetic SP transgenes containing multiple miRNA binding sites
      targeting different Arabidopsis miRNA families were generated. Additionally,
      their silencing efficacies were compared to the corresponding MIM and STTM
      transgenes via scoring the frequency and severity of phenotypic abnormalities
      elicited by each transgene. While SPs with wild-type miRNA binding sites have no
      apparent impact, SPs containing miRNA binding sites with two central mismatches
      (cmSPs) can generate strong loss-of-function phenotypes. However, their efficacy
      varied dramatically, from inducing strong loss-of-function phenotypes to failing
      to produce any phenotypic impact. Variability was also observed when MIMs and
      STTMs were compared to cmSPs. While cmSP165/166 and STTM165/166 showed a stronger
      efficacy than MIM165/166, MIM159 was stronger than cmSP159 and STTM159. Although
      increasing the number of miRNA binding sites or strengthening the free energy of
      the miRNA binding site interaction can improve decoy efficacy, clearly additional
      unknown overriding factors are at play. In conclusion, we demonstrate that no one
      approach guarantees the strongest miRNA inhibition, but rather distinct miRNA
      families respond differently to the various approaches, suggesting that multiple
      approaches may need to be taken to generate the desired loss-of-function outcome.

PMID- 25600075
TI  - Improved allele-specific PCR assays for detection of clarithromycin and
      fluoroquinolone resistant of Helicobacter pylori in gastric biopsies:
      identification of N87I mutation in GyrA.
AB  - Molecular testing can rapidly detect Helicobacter pylori susceptibility using
      gastric biopsies. Allele-specific polymerase chain reaction (ASP-PCR) was used to
      identify H. pylori 23S rRNA and gyrA mutation using gastric biopsies from
      Colombian patients and confirmed by PCR and sequencing of the 23S rRNA and gyrA
      genes. The sensitivity and specificity of ASP-PCR were compared with
      susceptibilities measured by agar dilution. Samples included gastric biopsies
      from 107 biopsies with H. pylori infections and 20 H. pylori negative. The
      sensitivity and specificity of ASP-PCR for the 23S rRNA gene were both 100%. The
      sensitivity and specificity of ASP-PCR for the gyrA gene, published in 2007 by
      Nishizawa et al., were 52% and 92.7%, respectively; the lower sensitivity was due
      to the presence of mutation N87I in our samples, which were not detected by the
      test. In this study, we designed new primers to detect the mutation N87I in GyrA.
      The ASP-PCR was performed with the original primers plus the new primers. The
      molecular test with the new primers improved the sensitivity to 100%. In
      conclusion, ASP-PCR provides a specific and rapid means of predicting resistance
      to clarithromycin and levofloxacin in gastric biopsies.

PMID- 25600076
TI  - Dental treatment for paediatric obstructive sleep apnea.
AB  - Paediatric obstructive sleep apnea (OSA) is common and its prevalence is expected
      to increase due to the rise in childhood obesity. Recent research has shown that
      many children, both syndromic and non-syndromic, who exhibit mouth breathing as a
      result of upper airway obstruction, may also exhibit dentofacial anomalies.
      Although adenotonsillectomy and continuous positive airway pressure have been
      classically proposed as the primary treatment modalities for paediatric OSA,
      there are significant limitations to both therapies. Therefore newer treatment
      modalities are needed. Current research has focused on emerging dental treatment
      options for paediatric OSA, such as rapid maxillary expansion, oral appliances
      and distraction osteogenesis. However, there are few randomized trials assessing
      the effectiveness of these novel dental therapies for paediatric OSA, and hence
      further research is required to advance the field. 

PMID- 25600077
TI  - Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath
      test.
AB  - BACKGROUND: The diagnosis of small intestinal bacterial overgrowth (SIBO) remains
      challenging. Our aim was to examine the diagnostic yield of duodenal
      aspiration/culture and glucose breath test (GBT), and effects of gender, race and
      demographics on prevalence of SIBO. METHODS: Patients with unexplained gas,
      bloating and diarrhea and negative endoscopy, imaging and blood tests were
      prospectively enrolled in two centers in USA. Randomly, within 1 week each
      patient underwent both duodenal aspiration/culture and GBT. The diagnostic yield
      of each test and relationship of symptoms, and effects of ethnicity, age, and
      gender on prevalence of SIBO were assessed and compared. KEY RESULTS: Duodenal
      culture was positive in 62/139 (44.6%) subjects and GBT was positive in 38/139
      (27.3%) subjects with an overall diagnostic agreement of 65.5%. The sensitivity,
      specificity, positive and negative predictive value of GBT was 42%, 84%, 68%, and
      64%, respectively. Ethnicity or gender did not influence SIBO, but SIBO positive
      patients were older (p = 0.0018). Symptom patterns were similar except bloating
      was more prevalent in GBT positive and gas in culture positive subjects.
      CONCLUSIONS & INFERENCES: Duodenal aspiration/culture identifies 45% of patients
      with suspected SIBO. GBT has lower sensitivity but good specificity for detection
      of SIBO. There were no ethnic or gender differences in the prevalence of SIBO,
      but patients with SIBO were older. Because GBT is non-invasive, it should be
      considered first in patients with suspected SIBO.

PMID- 25600078
TI  - A web-based data-querying tool based on ontology-driven methodology and flowchart
      based model.
AB  - BACKGROUND: Because of the increased adoption rate of electronic medical record
      (EMR) systems, more health care records have been increasingly accumulating in
      clinical data repositories. Therefore, querying the data stored in these
      repositories is crucial for retrieving the knowledge from such large volumes of
      clinical data. OBJECTIVE: The aim of this study is to develop a Web-based
      approach for enriching the capabilities of the data-querying system along the
      three following considerations: (1) the interface design used for query
      formulation, (2) the representation of query results, and (3) the models used for
      formulating query criteria. METHODS: The Guideline Interchange Format version 3.5
      (GLIF3.5), an ontology-driven clinical guideline representation language, was
      used for formulating the query tasks based on the GLIF3.5 flowchart in the
      Protege environment. The flowchart-based data-querying model (FBDQM) query
      execution engine was developed and implemented for executing queries and
      presenting the results through a visual and graphical interface. To examine a
      broad variety of patient data, the clinical data generator was implemented to
      automatically generate the clinical data in the repository, and the generated
      data, thereby, were employed to evaluate the system. The accuracy and time
      performance of the system for three medical query tasks relevant to liver cancer
      were evaluated based on the clinical data generator in the experiments with
      varying numbers of patients. RESULTS: In this study, a prototype system was
      developed to test the feasibility of applying a methodology for building a query
      execution engine using FBDQMs by formulating query tasks using the existing GLIF.
      The FBDQM-based query execution engine was used to successfully retrieve the
      clinical data based on the query tasks formatted using the GLIF3.5 in the
      experiments with varying numbers of patients. The accuracy of the three queries
      (ie, "degree of liver damage," "degree of liver damage when applying a mutually
      exclusive setting," and "treatments for liver cancer") was 100% for all four
      experiments (10 patients, 100 patients, 1000 patients, and 10,000 patients).
      Among the three measured query phases, (1) structured query language operations,
      (2) criteria verification, and (3) other, the first two had the longest execution
      time. CONCLUSIONS: The ontology-driven FBDQM-based approach enriched the
      capabilities of the data-querying system. The adoption of the GLIF3.5 increased
      the potential for interoperability, shareability, and reusability of the query
      tasks.

PMID- 25600079
TI  - Trans-pinnal movement of methimazole: an in vitro study showing that methimazole
      can cross from the inner to outer pinna of cats.
AB  - OBJECTIVES: The aim of the study was to determine if methimazole applied in a
      transdermal formulation to the internal pinna will cross to the external pinna in
      an in vitro Franz cell model. METHODS: The ears from six cats were harvested soon
      after death. Whole ears were mounted onto Franz-type diffusion cells with the
      stratum corneum of the inner pinnae uppermost. A commercial transdermal
      preparation containing methimazole (0.1 ml/10 mg) was applied to the inner
      pinnae. At 1, 2, 4, 6, 8, 12, 18, 24 and 30 h, a 200 ul sample of reservoir
      solution was removed to determine the methimazole concentration by high
      performance liquid chromatography. The ears were then dissected, separating the
      internal pinna from the cartilage and the external pinna, before the methimazole
      concentration was measured at each site. The thickness of the different regions
      of the ear was measured on paraffin histology sections. RESULTS: Mean +/- SD
      methimazole concentrations at 30 h for the right and left ear, respectively,
      were: inner ear, 1.25 +/- 0.53 mg/g, 0.39 +/- 0.26 mg/g; cartilage, 1.36 +/- 0.47
      mg/g, 0.33 +/- 0.20 mg/g; and outer ear, 1.0 +/- 0.32 mg/g, 0.33 +/- 0.14 mg/g.
      There was a difference between the left and right ears (P <0.001). Minimal
      methimazole concentrations were detected in the receptor fluid. The mean
      methimazole concentration absorbed by the skin after application of 10 mg was,
      for the right ear, 3.65 +/- 1.27 mg/g and, for the left, 1.08 +/- 0.27 mg/g.
      There was no correlation between methimazole concentrations and thickness of each
      region of the ear. CONCLUSIONS AND RELEVANCE: Methimazole in a lipophilic vehicle
      applied to the inner pinna will penetrate to the outer pinna of cats in an in
      vitro model, which may have safety implications for humans associated with cats
      treated with transdermal methimazole. Substantial inter-individual variation was
      found. Further research is required in the area of transdermal penetration of
      drugs in cats.

PMID- 25600080
TI  - Haematological and biochemical reference intervals in adult Maine Coon cat blood
      donors.
AB  - OBJECTIVES: The objectives of this study were to derive Maine Coon haematological
      and biochemical reference intervals (RIs) from adult healthy blood donors, to
      validate (or reject) the use of published RIs for the general feline population
      in this breed, and to evaluate the effects of age, sex and weight on the
      haematological and biochemical results. METHODS: Haematological and biochemical
      data were retrieved retrospectively from a database of 81 healthy adult Maine
      Coon cat blood donors and were analysed to generate normal RIs. RIs were
      determined and compared with established non-breed-specific feline RIs according
      to the Clinical and Laboratory Standards Institute guidelines and the American
      Society of Veterinary Clinical Pathology guidelines using Reference Value-Advisor
      (version 2.1) software. RESULTS: The age of the cats ranged from 1-8 years (mean
      4.4 years), 42 were female and 39 were male, and weights ranged from 4.9-8.5 kg
      (mean 6.7 kg). New Maine Coon RIs were proposed for red blood cell count, mean
      corpuscular volume, mean corpuscular haemoglobin concentration, reticulocyte
      count and percentage. Haematocrit was higher in male cats (mean HCT 42.9% vs 41%
      in females; P = 0.001) and in heavier cats (P = 0.003; slope 1.0, regression
      equation HCT = 35.1 + 1.0 * weight). New biochemical RIs were proposed for urea,
      aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), alkaline
      phosphatase, total protein and albumin in Maine Coons. Females had higher GGT
      (median GGT value in females 4.0 vs 3.0 in males; P = 0.011) and albumin values
      (mean albumin value 3.3 in females vs 3.1 in males; P = 0.013). CONCLUSIONS AND
      RELEVANCE: Currently published RIs for some haematological and biochemical
      parameters are not appropriate for use in adult Maine Coon cats. A breed-specific
      variation could be a plausible explanation for the new haematological and serum
      biochemical analytes proposed in this study. Breed-specific RIs for Maine Coon
      cats will help prevent misinterpretation of laboratory results in diagnosis and
      in the selection of ideal blood donors.

PMID- 25600081
TI  - Identification of Cytauxzoon felis infection in domestic cats from southern
      Illinois.
AB  - OBJECTIVES: The objective of this study was to document Cytauxzoon felis
      infection in domestic cats from southern Illinois. METHODS: Diagnosis of
      cytauxzoonosis was based upon clinical signs of illness and detection of
      piroplasms within erythrocytes on peripheral blood smears or schizonts in
      internal organs consistent with Cytauxzoon infection. Additionally, genomic DNA
      was extracted from histologic sections of splenic tissue from two cats. RESULTS:
      The internal transcribed spacer region-1 (ITS-1) and ITS-2 of the C felis genome
      were successfully sequenced, confirming infection with the organism. CONCLUSIONS
      AND RELEVANCE: Sequence analysis of C felis DNA isolated from histologic lesions
      in two domestic cats from southern Illinois show either mixed infection or
      possible heterozygosity (cytosine and thymine) in ITS-2 at the position
      equivalent to nucleotide 76 (thymine) in the most commonly isolated C felis ITS-2
      sequence. Identification of C felis infection in domestic cats from southern
      Illinois is a critical finding that raises awareness of this often fatal disease
      process in an area of the USA where, previously, the disease was only anecdotally
      reported.

PMID- 25600082
TI  - Comparison of axillary, tympanic membrane and rectal temperature measurement in
      cats.
AB  - OBJECTIVES: Rectal temperature (RT) is routinely used to assess body temperature
      in cats but has limitations and can be poorly tolerated. Axillary temperature
      (AT) and tympanic membrane temperature (TMT) are reported alternatives. This
      study aimed to determine the differences between RT and AT, and between RT and
      TMT in cats. Additional aims were to examine the effect of environmental and
      patient factors on these differences and to assess patient tolerance to each
      technique. METHODS: AT, TMT and RT were measured in immediate succession.
      Measurement order was randomised, as was the choice of left or right axilla and
      tympanic membrane. A digital thermometer and a veterinary infrared ear
      thermometer were used. The subjective tolerance of each procedure was recorded.
      RESULTS: One hundred and fifty cats were included. Significantly more conscious
      cats were tolerant of AT (90.6%) than TMT (81.2%) and RT (53.0%). The rectal
      axillary temperature difference ranged from -1.2 degrees C to 1.4 degrees C
      (median 0.1 degrees C) and was within +/- 0.5 degrees C in 78.0% of cats. On
      multivariable analysis the difference was larger in overweight cats, neutered
      cats, cats in which the right axilla was used and as the RT increased. The rectal
      tympanic membrane temperature difference ranged from -1.6 degrees C to 3 degrees
      C (median -0.3 degrees C) and was within +/- 0.5 degrees C in 51.3% of cats,
      significantly fewer than for AT (P <0.001). The rectal-tympanic membrane
      temperature difference increased as the RT increased. CONCLUSIONS AND RELEVANCE:
      TMT and AT should not be used interchangeably with RT in cats. When RT
      measurement is not possible, AT is recommended over TMT as it is better tolerated
      and significantly fewer cats had clinically unacceptable differences (>0.5
      degrees C). AT may more closely reflect RT in normal or underweight cats than it
      does in overweight cats.

PMID- 25600083
TI  - A novel aromatic carbocation-based coupling reagent for esterification and
      amidation reactions.
AB  - A novel tropylium-based coupling reagent has been developed to facilitate the
      synthesis of a series of esters, amides, lactones and peptides under mild
      reaction conditions. Remarkably, this reagent can be used in catalytic amounts in
      conjunction with a sacrificial reagent, offering a new and efficient method for
      nucleophilic coupling reactions of carboxylic acids. 

PMID- 25600084
TI  - Uric acid as a biomarker and a therapeutic target in diabetes.
AB  - Diabetic nephropathy is a long-standing microvascular complication of diabetes
      mellitus and is the leading cause of end stage renal disease in developed
      countries. Current therapeutic strategies used to prevent or delay diabetic
      nephropathy exert limited clinical protective effects and can have serious
      adverse effects. Thus, identification of new pharmacologic agents that protect
      against the initiation and progression of complications of diabetes is of the
      utmost importance. Uric acid (UA) recently emerged as an inflammatory factor that
      increases oxidative stress and promotes activation of the renin angiotensin
      aldosterone system. As a consequence, higher UA levels are associated with
      various stages of the onset and progression of diabetic nephropathy, including
      metabolic, cardiovascular and kidney function abnormalities. If UA-lowering
      drugs, such as the xanthine oxidase inhibitors, block the mechanisms responsible
      for micro- and macrovascular injury in diabetes, these agents could represent a
      critical step toward preventing the progression of diabetes. This review focuses
      on the evidence that supports serum UA levels as a biomarker of renal and
      cardiovascular risk and as a potential additional therapeutic target in diabetes.

PMID- 25600086
TI  - Divergent host preferences of above- and below-ground Culex pipiens mosquitoes
      and their hybrid offspring.
AB  - Culex pipiens form pipiens and Cx. pipiens form molestus (Diptera: Culicidae)
      belong to a cosmopolitan taxonomic group known as the Pipiens Assemblage.
      Hybridization between these forms is thought to contribute to human transmission
      of West Nile virus (WNV) in North America. Complementary choice and no-choice
      landing assays were developed to examine host acceptance by North American Cx.
      pipiens in the laboratory. Populations collected from above- and below-ground
      sites in suburban Chicago were identified as forms pipiens and molestus using a
      polymerase chain reaction-based assay. Avian and human host acceptance was then
      quantified for the two populations, as well as for their hybrid and backcross
      offspring. No-choice tests were used to demonstrate that both the pipiens and
      molestus forms were capable of feeding on human and avian hosts. Choice tests
      were used to demonstrate that form pipiens females were strongly avian-seeking;
      an individual's probability of accepting the chick host was 85%. Form molestus
      females were more likely to accept the human host (87%). Rates of host acceptance
      by F1 and backcross progeny were intermediate to those of their parents. The
      results suggest that host preferences in Cx. pipiens are genetically determined,
      and that ongoing hybridization between above- and below-ground populations is an
      important contributor to epizootic transmission of WNV in North America.

PMID- 25600085
TI  - Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term
      treatment effect in cat allergic subjects.
AB  - BACKGROUND: Cat-PAD, the first in a new class of synthetic peptide immuno
      regulatory epitopes (SPIREs), was shown to significantly improve
      rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the
      start of a short course of treatment. OBJECTIVE: To evaluate the long-term
      effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized
      allergen challenge 2 years after treatment. METHODS: In a randomized, double
      blind, placebo-controlled, parallel group study, subjects were exposed to cat
      allergen in an environmental exposure chamber (EEC) before and after treatment
      with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6
      nmol) given intradermally over a 3-month period. In this follow-up study, changes
      from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the
      start of treatment. RESULTS: The primary endpoint showed a mean reduction in
      total rhinoconjunctivitis symptom scores of 3.85 units in the 4 * 6 nmol Cat-PAD
      group compared to placebo 2 years after the start of treatment (P = 0.13), and
      this difference was statistically significant in the secondary endpoint at the
      end of day 4 when the cumulative allergen challenge was greatest (P = 0.02).
      Consistent reductions in nasal symptoms of between 2 and 3 units were observed
      for 4 * 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on
      days 1-4 of EEC challenge at 2 years (P < 0.05). The 8 * 3 nmol dose did not show
      a meaningful effect in this study. CONCLUSION AND CLINICAL RELEVANCE: A
      persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was
      observed on EEC challenge 2 years after the start of a short course of treatment
      with 4 * 6 nmol Cat-PAD. This study is the first to provide evidence of a long
      term therapeutic effect with this new class of SPIREs.

PMID- 25600087
TI  - Incorporation of personal single nucleotide polymorphism (SNP) data into a
      national level electronic health record for disease risk assessment, part 3: an
      evaluation of SNP incorporated national health information system of Turkey for
      prostate cancer.
AB  - BACKGROUND: A personalized medicine approach provides opportunities for
      predictive and preventive medicine. Using genomic, clinical, environmental, and
      behavioral data, the tracking and management of individual wellness is possible.
      A prolific way to carry this personalized approach into routine practices can be
      accomplished by integrating clinical interpretations of genomic variations into
      electronic medical records (EMRs)/electronic health records (EHRs). Today,
      various central EHR infrastructures have been constituted in many countries of
      the world, including Turkey. OBJECTIVE: As an initial attempt to develop a
      sophisticated infrastructure, we have concentrated on incorporating the personal
      single nucleotide polymorphism (SNP) data into the National Health Information
      System of Turkey (NHIS-T) for disease risk assessment, and evaluated the
      performance of various predictive models for prostate cancer cases. We present
      our work as a three part miniseries: (1) an overview of requirements, (2) the
      incorporation of SNP data into the NHIS-T, and (3) an evaluation of SNP data
      incorporated into the NHIS-T for prostate cancer. METHODS: In the third article
      of this miniseries, we have evaluated the proposed complementary capabilities
      (ie, knowledge base and end-user application) with real data. Before the
      evaluation phase, clinicogenomic associations about increased prostate cancer
      risk were extracted from knowledge sources, and published predictive genomic
      models assessing individual prostate cancer risk were collected. To evaluate
      complementary capabilities, we also gathered personal SNP data of four prostate
      cancer cases and fifteen controls. Using these data files, we compared various
      independent and model-based, prostate cancer risk assessment approaches. RESULTS:
      Through the extraction and selection processes of SNP-prostate cancer risk
      associations, we collected 209 independent associations for increased risk of
      prostate cancer from the studied knowledge sources. Also, we gathered six
      cumulative models and two probabilistic models. Cumulative models and assessment
      of independent associations did not have impressive results. There was one of the
      probabilistic, model-based interpretation that was successful compared to the
      others. In envirobehavioral and clinical evaluations, we found that some of the
      comorbidities, especially, would be useful to evaluate disease risk. Even though
      we had a very limited dataset, a comparison of performances of different disease
      models and their implementation with real data as use case scenarios helped us to
      gain deeper insight into the proposed architecture. CONCLUSIONS: In order to
      benefit from genomic variation data, existing EHR/EMR systems must be constructed
      with the capability of tracking and monitoring all aspects of personal health
      status (genomic, clinical, environmental, etc) in 24/7 situations, and also with
      the capability of suggesting evidence-based recommendations. A national-level,
      accredited knowledge base is a top requirement for improved end-user systems
      interpreting these parameters. Finally, categorization using similar, individual
      characteristics (SNP patterns, exposure history, etc) may be an effective way to
      predict disease risks, but this approach needs to be concretized and supported
      with new studies.

PMID- 25600089
TI  - Forbidden atomic transitions driven by an intensity-modulated laser trap.
AB  - Spectroscopy is an essential tool in understanding and manipulating quantum
      systems, such as atoms and molecules. The model describing spectroscopy includes
      the multipole-field interaction, which leads to established spectroscopic
      selection rules, and an interaction that is quadratic in the field, which is not
      often employed. However, spectroscopy using the quadratic (ponderomotive)
      interaction promises two significant advantages over spectroscopy using the
      multipole-field interaction: flexible transition rules and vastly improved
      spatial addressability of the quantum system. Here we demonstrate ponderomotive
      spectroscopy by using optical-lattice-trapped Rydberg atoms, pulsating the
      lattice light and driving a microwave atomic transition that would otherwise be
      forbidden by established spectroscopic selection rules. This ability to measure
      frequencies of previously inaccessible transitions makes possible improved
      determinations of atomic characteristics and constants underlying physics. The
      spatial resolution of ponderomotive spectroscopy is orders of magnitude better
      than the transition frequency would suggest, promising single-site addressability
      in dense particle arrays for quantum computing applications. 

PMID- 25600090
TI  - Simple and sensitive fluorescent and electrochemical trinitrotoluene sensors
      based on aqueous carbon dots.
AB  - Aqueous N-rich carbon dots (CDs), prepared by the microwave-assisted pyrolysis
      method, are applied as a dual sensing platform for both the fluorescent and
      electrochemical detection of 2,4,6-trinitrotoluene (TNT). The fluorescent sensing
      platform is established on the strong TNT-amino interaction which can quench the
      photoluminescence of amino functionalized CDs through charge transfer. The
      resultant linear detection ranges from 10 nM to 1.5 MUM with a fast response time
      of 30 s. Glassy carbon electrode modified with CDs exhibits a fine capability for
      TNT reduction with the linear range from 5 nM to 30 MUM, better than that
      obtained by the fluorescent method. Moreover, the minimum distinguishable
      response concentration with respect to these two methods is down to the nanomolar
      level with a high specificity and sensitivity. 

PMID- 25600088
TI  - Characterising two-pathogen competition in spatially structured environments.
AB  - Different pathogens spreading in the same host population often generate complex
      co-circulation dynamics because of the many possible interactions between the
      pathogens and the host immune system, the host life cycle, and the space
      structure of the population. Here we focus on the competition between two acute
      infections and we address the role of host mobility and cross-immunity in shaping
      possible dominance/co-dominance regimes. Host mobility is modelled as a network
      of traveling flows connecting nodes of a metapopulation, and the two-pathogen
      dynamics is simulated with a stochastic mechanistic approach. Results depict a
      complex scenario where, according to the relation among the epidemiological
      parameters of the two pathogens, mobility can either be non-influential for the
      competition dynamics or play a critical role in selecting the dominant pathogen.
      The characterisation of the parameter space can be explained in terms of the
      trade-off between pathogen's spreading velocity and its ability to diffuse in a
      sparse environment. Variations in the cross-immunity level induce a transition
      between presence and absence of competition. The present study disentangles the
      role of the relevant biological and ecological factors in the competition
      dynamics, and provides relevant insights into the spatial ecology of infectious
      diseases. 

PMID- 25600091
TI  - De novo assembly and comprehensive characterization of the skeletal muscle
      transcriptomes of the European anchovy (Engraulis encrasicolus).
AB  - European anchovy has considerable economic and ecological importance due to its
      high reproduction capacity and growth rate. As one of the largest source of wild
      marine protein, an increasing muscle mass strength has a major contribution to
      this growth rate during transition from subadult to adult stage. In the present
      study, using Illumina sequencing technology (HiSeq2000) accompanied with
      appropriate bioinformatics softwares; we have sequenced, assembled and annotated
      the transcriptome of wild subadult and adult anchovy muscles. A total of
      131,081,776 high-quality reads were assembled into 125,506 contigs with an
      average length of 709.35 bp and N50 length of 1159 bp. Functional annotations of
      assembled contigs have been summarized according to 3325 GO terms, 3370 PFAM
      domains and 378 predicted KEGG metabolic pathways. About 11% of all contigs had
      at least one type of SSR motif in their sequences. According to the sequence
      homology analysis by BlasTN it was concluded that the assembled contigs include
      16 skeletal muscle-expressed miRNAs, 14 ncRNAs and most of
      sarcomeric/myofibrillar genes. We hope that the sequence information regarding
      the muscle transcriptome of anchovy can provide some insight into the
      understanding of genome-wide transcriptome profile of teleost muscle tissue and
      give useful information in fish muscle development.

PMID- 25600093
TI  - Prostate cancer: New imaging method to improve prostate cancer detection.

PMID- 25600092
TI  - A multicenter study on dental trauma in permanent incisors among Special Olympics
      athletes in Europe and Eurasia.
AB  - BACKGROUND: Special Olympics athletes, as part of the population with
      intellectual disabilities, are reported to be more vulnerable to dental injuries
      due to poor lip closure, slow response to environmental obstacles, oral
      pathologic reflexes, or dental features. The aim of this study was to assess the
      prevalence of dental trauma among Special Olympics athletes in countries of
      Europe and Eurasia. MATERIAL AND METHODS: A retrospective longitudinal study was
      performed with data collected through standardized Special Smiles screening forms
      and procedures from consenting 15,941 athletes participating in the annual
      Special Olympics held in 49 countries from Europe and Eurasia between 2007 and
      2012. The data was compiled in an Excel worksheet and transferred to an SPSS data
      file in order to be analyzed. RESULTS: A total of 2190 athletes presented dental
      injury (13.02%) with a std. deviation of 5.02%, and there were no significant
      differences (p = 0.136) in mean dental injury between age groups (one-way ANOVA
      test). CONCLUSIONS: The present data suggest that dental trauma is an actual
      problem among individuals with special needs. The distribution of prevalence
      among the different countries had a remarkable variability, but it is evident
      that a relatively high proportion of this population is in need of dental trauma
      preventive programs.

PMID- 25600094
TI  - Kidney cancer in 2014: Key advances promise progress for kidney cancer patients.

PMID- 25600095
TI  - Kidney cancer: Systemic therapy--differentiating the achievable from the
      achieved.

PMID- 25600096
TI  - Prostate cancer: Effects of tertiary Gleason pattern 5 on oncological outcome.

PMID- 25600097
TI  - Prostate cancer in 2014: The year chemotherapy finally gets some respect!

PMID- 25600100
TI  - Laparoscopic promonto-fixation for urogenital prolapsus.

PMID- 25600099
TI  - Influence of trans fat on skin damage in first-generation rats exposed to UV
      radiation.
AB  - The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and
      mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR)
      was assessed. The first-generation offspring of female Wistar rats supplemented
      from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or
      hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same
      supplements until adulthood, when half of each group was exposed to UVR for 12
      weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein
      carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and
      antioxidant defenses of the skin. After UVR, the HVF group showed increased skin
      thickness and reactive species (RS) generation, with decreased skin antioxidant
      defenses. RS generation was positively correlated with skin thickness, wrinkles
      and PC levels. Once incorporated to skin, TFA make it more susceptible to
      developing UVR-induced disorders. 

PMID- 25600098
TI  - The microbiome of the urinary tract--a role beyond infection.
AB  - Urologists rarely need to consider bacteria beyond their role in infectious
      disease. However, emerging evidence shows that the microorganisms inhabiting many
      sites of the body, including the urinary tract--which has long been assumed
      sterile in healthy individuals--might have a role in maintaining urinary health.
      Studies of the urinary microbiota have identified remarkable differences between
      healthy populations and those with urologic diseases. Microorganisms at sites
      distal to the kidney, bladder and urethra are likely to have a profound effect on
      urologic health, both positive and negative, owing to their metabolic output and
      other contributions. Connections between the gut microbiota and renal stone
      formation have already been discovered. In addition, bacteria are also used in
      the prevention of bladder cancer recurrence. In the future, urologists will need
      to consider possible influences of the microbiome in diagnosis and treatment of
      certain urological conditions. New insights might provide an opportunity to
      predict the risk of developing certain urological diseases and could enable the
      development of innovative therapeutic strategies.

PMID- 25600101
TI  - Unexpected manifestation of naevoid basal cell carcinoma (Gorlin) syndrome with a
      novel mutation in the PTCH1 gene in a female patient with long-lasting pemphigus
      vulgaris.

PMID- 25600103
TI  - (47)Ca production for (47)Ca/(47)Sc generator system using electron linacs.
AB  - In this work we have studied the feasibility of photonuclear production of (47)Ca
      from (48)Ca for (47)Ca/(47)Sc generators. Photon flux distribution for electron
      beams of different energies incident on a tungsten converter was calculated using
      the MCNPX radiation transport code. The (47)Ca production rate dependence on
      electron beam energy was found and (47)Ca/(47)Sc yields were estimated for a
      40MeV electron beam. It was shown that irradiating enriched targets with a 40MeV,
      1mA beam will result in tens of MBq g(-1) (few mCi g(-1)) activity of (47)Sc. The
      results of the simulations were benchmarked by irradiating 22.5g of CaCl2 powder
      with a 39MeV electron beam incident on a tungsten converter. Measured
      (47)Ca/(47)Sc activities were found to be in very good agreement with the
      predictions. 

PMID- 25600102
TI  - Antidepressant-like effect of zinc is dependent on signaling pathways implicated
      in BDNF modulation.
AB  - Considering that intracellular signaling pathways that modulate brain BDNF are
      implicated in antidepressant responses, this study investigated whether signaling
      pathway inhibitors upstream to BDNF might influence the antidepressant-like
      effect of zinc, a metal that has been shown to display antidepressant properties.
      To this end, the influence of i.c.v. administration of H-89 (1MUg/site, PKA
      inhibitor), KN-62 (1MUg/site, CAMKII inhibitor), chelerythrine (1MUg/site, PKC
      inhibitor), PD98059 (5MUg/site, MEK1/2 inhibitor), U0126 (5MUg/site, MEK1/2
      inhibitor), LY294002 (10nmol/site, PI3K inhibitor) on the reduction of immobility
      time in the tail suspension test (TST) elicited by ZnCl2 (10mg/kg, p.o.) was
      investigated. Moreover, the effect of the combination of sub-effective doses of
      ZnCl2 (1mg/kg, p.o.) and AR-A014418 (0.001MUg/site, GSK-3beta inhibitor) was
      evaluated. The occurrence of changes in CREB phosphorylation and BDNF
      immunocontent in the hippocampus and prefrontal cortex of mice following ZnCl2
      treatment was also investigated. The anti-immobility effect of ZnCl2 in the TST
      was prevented by treatment with PKA, PKC, CAMKII, MEK1/2 or PI3K inhibitors.
      Furthermore, ZnCl2 in combination with AR-A014418 caused a synergistic anti
      immobility effect in the TST. None of the treatments altered locomotor activity
      of mice. ZnCl2 treatment caused no alteration in CREB phosphorylation and BDNF
      immunocontent. The results extend literature data regarding the mechanisms
      underlying the antidepressant-like action of zinc by indicating that its
      antidepressant-like effect may be dependent on the activation of PKA, CAMKII,
      PKC, ERK, and PI3K/GSK-3beta pathways. However, zinc is not able to acutely
      increase BDNF in the hippocampus and prefrontal cortex. 

PMID- 25600104
TI  - Abecedarium: Who Am I? V'....

PMID- 25600105
TI  - Coronary calcium score in 12-year breast cancer survivors after adjuvant
      radiotherapy with low to moderate heart exposure - Relationship to cardiac
      radiation dose and cardiovascular risk factors.
AB  - BACKGROUND/PURPOSE: We explored the relation between coronary artery calcium
      (CAC) and cardiac radiation doses in breast cancer survivors (BCS) treated with
      radiotherapy (RT). Additionally, we examined the impact of other risk factors and
      biomarkers of coronary artery disease (CAD). MATERIALS AND METHODS: 236 BCS
      (median age 51years [range 30-70], median observation time 12years [9.2-15.7]),
      treated with 4-field RT of 50GY, were included and examined in 2004 (T1), 2007
      (T2) and 2011 (T3) with clinical examination, blood tests and questionnaires. At
      T3, cardiac computed tomography was performed with quantification of CAC using
      Agatston score (AS). For 106 patients cardiac dose volume histograms were
      available. RESULTS: The cohort-based median of the mean cardiac dose was 2.5
      (range 0.5-7.0) Gy. There was no correlation between measures of cardiac dose and
      AS. AS was correlated with high cholesterol at T1/T2 (p=0.022), high proBNP at
      T1/T2 (p<0.022) and T3 (p<0.022) and high HbA1c at T3 (p=0.022). In addition, a
      high AS was significantly associated with hypertension (p=0.022). Age (p<0.001)
      and cholesterol at T1/T2 (p=0.001) retained significant associations in
      multivariate analysis. CONCLUSIONS: Traditional, modifiable risk factors of CAD
      correlate with CAC and may be important for the long term risk of CAD after RT.
      With low to moderate cardiac radiation exposure, a contribution of radiation dose
      to CAC could not be demonstrated.

PMID- 25600107
TI  - [Use of bone graft replacement in spinal fusions].
AB  - BACKGROUND: The rationale for the increasing use of bone graft replacement lies
      in the need for increased graft volume, the avoidance of typical autograft donor
      site morbidity, and the potential improvement of fusion rates in revision and
      complex reconstructive surgery. OBJECTIVES: The purpose of this work is to offer
      the spinal surgeon an evidence-based guide for choosing the appropriate grafting
      material and for using it effectively. MATERIAL AND METHODS: Evidence-based
      overview of physical and biological properties, clinical indications and results
      of osteoconductive and osteoinductive bone replacement materials. RESULTS: The
      ideal bone replacement material should be osteoinductive and conductive, non
      pathogenic, minimally antigenic, and (if required) mechanically stable. Compared
      to autograft, vascularization and remodeling of the fusion mass are delayed using
      allograft. Allogenous bone and demineralized bone matrix (DBM) possess limited
      osteoinductive properties and carry the risk of potential infectious disease
      transmission. Plasma-rich plasma (PRP) and bone marrow aspirate are commonly used
      in conjunction with an osteoconductive carrier materials. On-label use of bone
      morphogenetic proteins (BMPs) is currently restricted to mono- and bisegmental
      anterior lumbar fusion. The fusion rates obtained with BMPs match those of
      autologous bone graft. Potential risks of rhBMP in clinical use include soft
      tissue reactions, radiculitis and potentially increased risk of cancer.
      Osteoconductive ceramics (HA, CC, CS, beta-TCP) are useful graft extenders and
      carriers for bone growth enhancers and antibiotics. CONCLUSIONS: Osteoconductive
      bioceramics with different mechanical and biological properties are available for
      use as graft extenders. In a defined group of anterior interbody fusion
      procedures (ACDF, ALIF), satisfactory fusion rates (> 90%) may be obtained with
      exclusive use of graft extenders, whereas their solitary use in posterolateral
      fusions is not advisable. Genuine bone replacement is currently feasible with
      BMPs. Their use should be restricted to specific indications such as complex
      revision surgery and pseudarthrosis.

PMID- 25600106
TI  - Antiretrovirals for primary HIV prevention: the current status of pre- and post
      exposure prophylaxis.
AB  - In light of the 2 million HIV infections that occur globally each year, there is
      a need to optimize strategies that integrate biomedical and behavioral approaches
      to HIV prevention. Post-exposure prophylaxis (PEP) immediately after acute high
      risk exposures and pre-exposure prophylaxis (PrEP) for those who engage in
      recurrent high-risk behaviors are promising bio-behavioral approaches to
      decreasing HIV transmission. Guidelines have recommended PEP for occupational and
      non-occupational exposures for over 15 years, but uptake of PEP has been limited,
      partly as a result of insufficient awareness of this intervention among persons
      at highest risk for acquiring HIV. However, since the publication of large
      randomized clinical trials demonstrating the efficacy of PrEP, and the
      dissemination of guidelines endorsing its use, there is a renewed focus on bio
      behavioral prevention. Numerous studies have recently assessed the acceptability
      of bio-behavioral prevention programs among diverse populations or described
      experiences implementing these programs in "real-world" settings. As research and
      clinical data informing optimal utilization of PEP and PrEP are rapidly
      accumulating, this review provides a timely summary of recent progress in bio
      behavioral prevention. By contextualizing the most noteworthy recent findings
      regarding PEP and PrEP, this review seeks to inform the successful implementation
      of these promising prevention approaches. 

PMID- 25600108
TI  - It still hurts: altered endogenous opioid activity in the brain during social
      rejection and acceptance in major depressive disorder.
AB  - The MU-opioid receptor (MOR) system, well known for dampening physical pain, is
      also hypothesized to dampen 'social pain.' We used positron emission tomography
      scanning with the selective MOR radioligand [(11)C]carfentanil to test the
      hypothesis that MOR system activation (reflecting endogenous opioid release) in
      response to social rejection and acceptance is altered in medication-free
      patients diagnosed with current major depressive disorder (MDD, n=17) compared
      with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced
      endogenous opioid release in brain regions regulating stress, mood and
      motivation, and slower emotional recovery compared with HCs. During acceptance,
      only HCs showed increased social motivation, which was positively correlated with
      endogenous opioid release in the nucleus accumbens, a reward structure. Altered
      endogenous opioid activity in MDD may hinder emotional recovery from negative
      social interactions and decrease pleasure derived from positive interactions.
      Both effects may reinforce depression, trigger relapse and contribute to poor
      treatment outcomes. 

PMID- 25600109
TI  - Somatostatin, neuronal vulnerability and behavioral emotionality.
AB  - Somatostatin (SST) deficits are common pathological features in depression and
      other neurological disorders with mood disturbances, but little is known about
      the contribution of SST deficits to mood symptoms or causes of these deficits.
      Here we show that mice lacking SST (Sst(KO)) exhibit elevated behavioral
      emotionality, high basal plasma corticosterone and reduced gene expression of
      Bdnf, Cortistatin and Gad67, together recapitulating behavioral, neuroendocrine
      and molecular features of human depression. Studies in Sst(KO) and heterozygous
      (Sst(HZ)) mice show that elevated corticosterone is not sufficient to reproduce
      the behavioral phenotype, suggesting a putative role for Sst cell-specific
      molecular changes. Using laser capture microdissection, we show that cortical SST
      positive interneurons display significantly greater transcriptome deregulations
      after chronic stress compared with pyramidal neurons. Protein translation through
      eukaryotic initiation factor 2 (EIF2) signaling, a pathway previously implicated
      in neurodegenerative diseases, was most affected and suppressed in stress-exposed
      SST neurons. We then show that activating EIF2 signaling through EIF2 kinase
      inhibition mitigated stress-induced behavioral emotionality in mice. Taken
      together, our data suggest that (1) low SST has a causal role in mood-related
      phenotypes, (2) deregulated EIF2-mediated protein translation may represent a
      mechanism for vulnerability of SST neurons and (3) that global EIF2 signaling has
      antidepressant/anxiolytic potential. 

PMID- 25600111
TI  - Levothyroxine effects on depressive symptoms and limbic glucose metabolism in
      bipolar disorder: a randomized, placebo-controlled positron emission tomography
      study.
AB  - Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for
      bipolar depression shows promise, but the mechanisms underlying clinical
      improvement are unknown. In a previous pilot study, L-T4 treatment reduced
      depression scores and activity within the anterior limbic network. Here we
      extended this work in a randomized, double-blind, placebo-controlled study of
      patients with bipolar depression. Cerebral glucose metabolism was assessed with
      positron emission tomography and [F-18]fluorodeoxyglucose before and after 6
      weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest
      (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and
      ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex.
      Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a
      surrogate index of glucose metabolism, and markers of thyroid function were
      assayed. Changes in brain activity and their association with clinical response
      were assessed using statistical parametric mapping. Adjunctive L-T4 treatment
      produced a significant decline in depression scores during the 6-week treatment.
      In patients treated with L-T4, we found a significant decrease in regional
      activity at P<0.05 after Bonferroni correction in the left thalamus, right
      amygdala, right hippocampus, left ventral striatum and the right dorsal striatum.
      Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate
      were correlated with a reduction in depression scores (P<0.05 after Bonferroni
      correction). Placebo treatment was associated with a significant decrease in
      activity only in the right amygdala, and no region had a change in activity that
      was correlated with change in depression scores. The groups differed
      significantly in the relationship between the changes in depression scores and in
      activity in the thalamus bilaterally and the left ventral striatum. The findings
      provide evidence that administration of supraphysiologic thyroid hormone improves
      depressive symptoms in patients with bipolar disorder by modulating function in
      components of the anterior limbic network. 

PMID- 25600110
TI  - Ovarian steroids regulate gene expression related to DNA repair and
      neurodegenerative diseases in serotonin neurons of macaques.
AB  - Depression often accompanies the perimenopausal transition and it often precedes
      overt symptomology in common neurodegenerative diseases (NDDs, such as
      Alzheimer's, Parkinson's, Huntington, amyotrophic lateral sclerosis). Serotonin
      dysfunction is frequently found in the different etiologies of depression. We
      have shown that ovariectomized (Ovx) monkeys treated with estradiol (E) for 28
      days supplemented with placebo or progesterone (P) on days 14-28 had reduced DNA
      fragmentation in serotonin neurons of the dorsal raphe nucleus, and long-term Ovx
      monkeys had fewer serotonin neurons than intact controls. We questioned the
      effect of E alone or E+P (estradiol supplemented with progesterone) on gene
      expression related to DNA repair, protein folding (chaperones), the ubiquitin
      proteosome, axon transport and NDD-specific genes in serotonin neurons. Ovx
      macaques were treated with placebo, E or E+P (n=3 per group) for 1 month.
      Serotonin neurons were laser captured and subjected to microarray analysis and
      quantitative real-time PCR (qRT-PCR). Increases were confirmed with qRT-PCR in
      five genes that code for proteins involved in repair of strand breaks and
      nucleotide excision. NBN1, PCNA (proliferating nuclear antigen), GADD45A (DNA
      damage-inducible), RAD23A (DNA damage recognition) and GTF2H5 (gene transcription
      factor 2H5) significantly increased with E or E+P treatment (all analysis of
      variance (ANOVA), P<0.01). Chaperone genes HSP70 (heat-shock protein 70), HSP60
      and HSP27 significantly increased with E or E+P treatment (all ANOVA, P<0.05).
      HSP90 showed a similar trend. Ubiquinase coding genes UBEA5, UBE2D3 and UBE3A
      (Parkin) increased with E or E+P (all ANOVA, P<0.003). Transport-related genes
      coding kinesin, dynein and dynactin increased with E or E+P treatment (all ANOVA,
      P<0.03). SCNA (alpha-synuclein) and ADAM10 (alpha-secretase) increased (both
      ANOVA, P<0.02) but PSEN1 (presenilin1) decreased (ANOVA, P<0.02) with treatment.
      APP decreased 10-fold with E or E+P administration. Newman-Keuls post hoc
      comparisons indicated variation in the response to E alone versus E+P across the
      different genes. In summary, E or E+P increased gene expression for DNA repair
      mechanisms in serotonin neurons, thereby rendering them less vulnerable to stress
      induced DNA fragmentation. In addition, E or E+P regulated four genes encoding
      proteins that are often misfolded or malfunctioning in neuronal populations
      subserving overt NDD symptomology. The expression and regulation of these genes
      in serotonergic neurons invites speculation that they may mediate an underlying
      disease process in NDDs, which in turn may be ameliorated or delayed with timely
      hormone therapy in women. 

PMID- 25600113
TI  - A potential life-threatening complication after implantation of a bioresorbable
      scaffold for coronary stenting within a mechanically stressed region.

PMID- 25600112
TI  - The molecular genetic architecture of attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral
      condition which affects 2-10% of school age children worldwide. Although the
      underlying molecular mechanism for the disorder is poorly understood, familial,
      twin and adoption studies suggest a strong genetic component. Here we provide a
      state-of-the-art review of the molecular genetics of ADHD incorporating evidence
      from candidate gene and linkage designs, as well as genome-wide association (GWA)
      studies of common single-nucleotide polymorphisms (SNPs) and rare copy number
      variations (CNVs). Bioinformatic methods such as functional enrichment analysis
      and protein-protein network analysis are used to highlight biological processes
      of likely relevance to the aetiology of ADHD. Candidate gene associations of
      minor effect size have been replicated across a number of genes including SLC6A3,
      DRD5, DRD4, SLC6A4, LPHN3, SNAP-25, HTR1B, NOS1 and GIT1. Although case-control
      SNP-GWAS have had limited success in identifying common genetic variants for ADHD
      that surpass critical significance thresholds, quantitative trait designs suggest
      promising associations with Cadherin13 and glucose-fructose oxidoreductase domain
      1 genes. Further, CNVs mapped to glutamate receptor genes (GRM1, GRM5, GRM7 and
      GRM8) have been implicated in the aetiology of the disorder and overlap with
      bioinformatic predictions based on ADHD GWAS SNP data regarding enriched
      pathways. Although increases in sample size across multi-center cohorts will
      likely yield important new results, we advocate that this must occur in parallel
      with a shift away from categorical case-control approaches that view ADHD as a
      unitary construct, towards dimensional approaches that incorporate endophenotypes
      and statistical classification methods. 

PMID- 25600114
TI  - Developing graduate student competency in providing culturally sensitive end of
      life care in critical care environments - a pilot study of a teaching innovation.
AB  - BACKGROUND: Australia's immigration policy has generated a rich diverse cultural
      community of staff and patients in critical care environments. Many different
      cultural perspectives inform individual actions in the context of critical care,
      including the highly sensitive area of end of life care, with nurses feeling
      poorly prepared to provide culturally sensitive end of life care. PURPOSE: This
      article describes and evaluates the effectiveness of an educational innovation
      designed to develop graduate-level critical care nurses' capacity for effective
      interpersonal communication, as members of a multi-disciplinary team in providing
      culturally sensitive end-of-life care. METHODS: A mixed method pilot study was
      conducted using a curriculum innovation intervention informed by The Excellence
      in Cultural Experiential Learning and Leadership Program (EXCELL),(1) which is a
      higher education intervention which was applied to develop the nurses'
      intercultural communication skills. 12 graduate nursing students studying
      critical care nursing participated in the study. 42% (n=5) of the participants
      were from an international background. Information about students' cultural
      learning was recorded before and after the intervention, using a cultural
      learning development scale. Student discussions of end of life care were recorded
      at Week 2 and 14 of the curriculum. The quantitative data was analysed using
      descriptive statistical analysis and qualitative data was thematically analysed.
      RESULTS: Students demonstrated an increase in cultural learning in a range of
      areas in the pre-post surveys including understandings of cultural diversity,
      interpersonal skills, cross cultural interactions and participating in
      multicultural groups. Thematic analysis of the end of life discussions revealed
      an increase in the levels of nurse confidence in approaching end of life care in
      critical care environments. CONCLUSION: The EXCELL program provides an effective
      and supportive educational framework to increase graduate nurses' cultural
      learning development and competence to manage culturally complex clinical issues
      such as end of life care, and is recommended as a framework for health care
      students to learn the skills required to provide culturally competent care in a
      range of culturally complex health care settings.

PMID- 25600115
TI  - Digestive peptidase evolution in holometabolous insects led to a divergent group
      of enzymes in Lepidoptera.
AB  - Trypsins and chymotrypsins are well-studied serine peptidases that cleave peptide
      bonds at the carboxyl side of basic and hydrophobic L-amino acids, respectively.
      These enzymes are largely responsible for the digestion of proteins. Three
      primary processes regulate the activity of these peptidases: secretion, precursor
      (zymogen) activation and substrate-binding site recognition. Here, we present a
      detailed phylogenetic analysis of trypsins and chymotrypsins in three orders of
      holometabolous insects and reveal divergent characteristics of Lepidoptera
      enzymes in comparison with those of Coleoptera and Diptera. In particular,
      trypsin subsite S1 was more hydrophilic in Lepidoptera than in Coleoptera and
      Diptera, whereas subsites S2-S4 were more hydrophobic, suggesting different
      substrate preferences. Furthermore, Lepidoptera displayed a lineage-specific
      trypsin group belonging only to the Noctuidae family. Evidence for facilitated
      trypsin auto-activation events were also observed in all the insect orders
      studied, with the characteristic zymogen activation motif complementary to the
      trypsin active site. In contrast, insect chymotrypsins did not seem to have a
      peculiar evolutionary history with respect to their mammal counterparts. Overall,
      our findings suggest that the need for fast digestion allowed holometabolous
      insects to evolve divergent groups of peptidases with high auto-activation rates,
      and highlight that the evolution of trypsins led to a most diverse group of
      enzymes in Lepidoptera.

PMID- 25600118
TI  - Robust ultrasonic damage detection under complex environmental conditions using
      singular value decomposition.
AB  - Guided wave ultrasonics is an attractive monitoring technique for damage
      diagnosis in large-scale plate and pipe structures. Damage can be detected by
      comparing incoming records with baseline records collected on intact structure.
      However, during long-term monitoring, environmental and operational conditions
      often vary significantly and produce large changes in the ultrasonic signals,
      thereby challenging the baseline comparison based damage detection. Researchers
      developed temperature compensation methods to eliminate the effects of
      temperature variation, but they have limitations in practical implementations. In
      this paper, we develop a robust damage detection method based on singular value
      decomposition (SVD). We show that the orthogonality of singular vectors ensures
      that the effect of damage and that of environmental and operational variations
      are separated into different singular vectors. We report on our field ultrasonic
      monitoring of a 273.05 mm outer diameter pipe segment, which belongs to a hot
      water piping system in continuous operation. We demonstrate the efficacy of our
      method on experimental pitch-catch records collected during seven months. We show
      that our method accurately detects the presence of a mass scatterer, and is
      robust to the environmental and operational variations exhibited in the practical
      system.

PMID- 25600116
TI  - Glycolytic enzymes localize to ribonucleoprotein granules in Drosophila germ
      cells, bind Tudor and protect from transposable elements.
AB  - Germ cells give rise to all cell lineages in the next-generation and are
      responsible for the continuity of life. In a variety of organisms, germ cells and
      stem cells contain large ribonucleoprotein granules. Although these particles
      were discovered more than 100 years ago, their assembly and functions are not
      well understood. Here we report that glycolytic enzymes are components of these
      granules in Drosophila germ cells and both their mRNAs and the enzymes themselves
      are enriched in germ cells. We show that these enzymes are specifically required
      for germ cell development and that they protect their genomes from transposable
      elements, providing the first link between metabolism and transposon silencing.
      We further demonstrate that in the granules, glycolytic enzymes associate with
      the evolutionarily conserved Tudor protein. Our biochemical and single-particle
      EM structural analyses of purified Tudor show a flexible molecule and suggest a
      mechanism for the recruitment of glycolytic enzymes to the granules. Our data
      indicate that germ cells, similarly to stem cells and tumor cells, might prefer
      to produce energy through the glycolytic pathway, thus linking a particular
      metabolism to pluripotency.

PMID- 25600117
TI  - Epigenetic predisposition to reprogramming fates in somatic cells.
AB  - Reprogramming to pluripotency is a low-efficiency process at the population
      level. Despite notable advances to molecularly characterize key steps, several
      fundamental aspects remain poorly understood, including when the potential to
      reprogram is first established. Here, we apply live-cell imaging combined with a
      novel statistical approach to infer when somatic cells become fated to generate
      downstream pluripotent progeny. By tracing cell lineages from several divisions
      before factor induction through to pluripotent colony formation, we find that pre
      induction sister cells acquire similar outcomes. Namely, if one daughter cell
      contributes to a lineage that generates induced pluripotent stem cells (iPSCs),
      its paired sibling will as well. This result suggests that the potential to
      reprogram is predetermined within a select subpopulation of cells and heritable,
      at least over the short term. We also find that expanding cells over several
      divisions prior to factor induction does not increase the per-lineage likelihood
      of successful reprogramming, nor is reprogramming fate correlated to neighboring
      cell identity or cell-specific reprogramming factor levels. By perturbing the
      epigenetic state of somatic populations with Ezh2 inhibitors prior to factor
      induction, we successfully modulate the fraction of iPSC-forming lineages. Our
      results therefore suggest that reprogramming potential may in part reflect
      preexisting epigenetic heterogeneity that can be tuned to alter the cellular
      response to factor induction. 

PMID- 25600121
TI  - [Non-pharmacological intervention in patients with mild Alzheimer's disease].

PMID- 25600119
TI  - Influence of clinician characteristics and operational factors on recruitment of
      participants with low back pain: an observational study.
AB  - OBJECTIVE: The purpose of this study was to identify factors that influence
      recruitment of patients to an observational study of low back pain (LBP).
      METHODS: From 1147 primary care (first health contact) clinicians initially
      contacted, 138 (physiotherapists and chiropractors) agreed to participate in a
      large observational study of LBP and were the focus of the current study. Data
      were collected pertaining to clinicians' characteristics, operational factors,
      and the number of patients recruited. The association of a variety of clinician
      characteristics and operational factors with recruitment rate was determined
      using a multivariate negative binomial regression analysis. RESULTS: From October
      2011 to November 2012, 1585 patients were screened by 138 study clinicians with
      951 eligible patients entering the observational study. Clinicians who were
      members of their professional association had a recruitment rate less than half
      that of those who were nonmembers (P < .0001). Clinicians who were trained by
      telephone had a recruitment rate 4.01 times higher than those trained face to
      face (P < .0001). Similarly, clinicians who referred a larger number of
      ineligible participants had a slightly higher recruitment rate with an incident
      rate ratio of 1.04 per ineligible patient (P < .0001). Other clinicians'
      characteristics and operational factors were not associated with recruitment.
      CONCLUSION: This study provides evidence that it is feasible to recruit
      participants from primary care practices to a simple observational study of LBP.
      Factors identified as influencing recruitment were professional association
      (negative association), training by telephone, and referring a higher number of
      ineligible participants.

PMID- 25600120
TI  - [Teaching geriatrics in undergraduate medicine].

PMID- 25600122
TI  - Theory of the formation of the electric double layer at the ion exchange membrane
      solution interface.
AB  - This work aims to extend the study of the formation of the electric double layer
      at the interface defined by a solution and an ion-exchange membrane on the basis
      of the Nernst-Planck and Poisson equations, including different values of the
      counter-ion diffusion coefficient and the dielectric constant in the solution and
      membrane phases. The network simulation method is used to obtain the time
      evolution of the electric potential, the displacement electric vector, the
      electric charge density and the ionic concentrations at the interface between a
      binary electrolyte solution and a cation-exchange membrane with total co-ion
      exclusion. The numerical results for the temporal evolution of the interfacial
      electric potential and the surface electric charge are compared with analytical
      solutions derived in the limit of the shortest times by considering the Poisson
      equation for a simple cationic diffusion process. The steady-state results are
      justified from the Gouy-Chapman theory for the diffuse double layer in the limits
      of similar and high bathing ionic concentrations with respect to the fixed-charge
      concentration inside the membrane. Interesting new physical insights arise from
      the interpretation of the process of the formation of the electric double layer
      at the ion exchange membrane-solution interface on the basis of a membrane model
      with total co-ion exclusion. 

PMID- 25600123
TI  - Antimicrobial prophylaxis for contaminated head and neck surgery. 1984.

PMID- 25600124
TI  - A sensorimotor role for traveling waves in primate visual cortex.
AB  - Traveling waves of neural activity are frequently observed to occur in concert
      with the presentation of a sensory stimulus or the execution of a movement.
      Although such waves have been studied for decades, little is known about their
      function. Here we show that traveling waves in the primate extrastriate visual
      cortex provide a means of integrating sensory and motor signals. Specifically, we
      describe a traveling wave of local field potential (LFP) activity in cortical
      area V4 of macaque monkeys that is triggered by the execution of saccadic eye
      movements. These waves sweep across the V4 retinotopic map, following a
      consistent path from the foveal to the peripheral representations of space; their
      amplitudes correlate with the direction and size of each saccade. Moreover, these
      waves are associated with a reorganization of the postsaccadic neuronal firing
      patterns, which follow a similar retinotopic progression, potentially
      prioritizing the processing of behaviorally relevant stimuli.

PMID- 25600125
TI  - Specific IgE positivity against inhalant allergens and development of autoimmune
      disease.
AB  - BACKGROUND: Allergic and autoimmune diseases have been suggested to be inversely
      associated. We investigated the association between atopy and development of any
      and specific types of autoimmune disease. METHODS: We included a total of 14,849
      individuals from five population-based studies with measurements of atopy defined
      as specific IgE positivity against inhalant allergens. We followed the
      participants by linkage to the Danish National Patient Register (median follow-up
      time 11.2 years). Hazard ratio (HR) and 95% confidence interval (CI) of
      autoimmune disease were estimated by Cox regression. RESULTS: The risk for
      atopics versus non-atopics was: for any autoimmune disease (HR = 0.99, 95% CI:
      0.83, 1.18), thyrotoxicosis (HR = 0.69, 95% CI: 0.34, 1.37), type 1 diabetes (HR
      = 1.16, 95% CI: 0.84, 1.60), multiple sclerosis (HR = 1.97, 95% CI: 0.95, 4.11),
      iridocyclitis (HR = 0.82, 95% CI: 0.38, 1.74), Crohn's disease (HR = 1.03, 95%
      CI: 0.47, 2.25), ulcerative colitis (HR = 0.93, 95% CI: 0.52, 1.69), psoriasis
      vulgaris (HR = 1.50, 95% CI: 0.86, 2.62), seropositive rheumatoid arthritis (HR =
      0.74, 95% CI: 0.48, 1.14) and polymyalgia rheumatica (HR = 0.79, 95% CI: 0.44,
      1.44). CONCLUSIONS: We found no statistically significant associations between
      atopy and autoimmune disease, but we cannot exclude relatively small to moderate
      effects - protective or promotive - of atopy on autoimmune disease.

PMID- 25600126
TI  - A comparison of heuristic and model-based clustering methods for dietary pattern
      analysis.
AB  - OBJECTIVE: Cluster analysis is widely applied to identify dietary patterns. A new
      method based on Gaussian mixture models (GMM) seems to be more flexible compared
      with the commonly applied k-means and Ward's method. In the present paper, these
      clustering approaches are compared to find the most appropriate one for
      clustering dietary data. DESIGN: The clustering methods were applied to simulated
      data sets with different cluster structures to compare their performance knowing
      the true cluster membership of observations. Furthermore, the three methods were
      applied to FFQ data assessed in 1791 children participating in the IDEFICS
      (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects
      in Children and Infants) Study to explore their performance in practice. RESULTS:
      The GMM outperformed the other methods in the simulation study in 72 % up to 100
      % of cases, depending on the simulated cluster structure. Comparing the
      computationally less complex k-means and Ward's methods, the performance of k
      means was better in 64-100 % of cases. Applied to real data, all methods
      identified three similar dietary patterns which may be roughly characterized as a
      'non-processed' cluster with a high consumption of fruits, vegetables and
      wholemeal bread, a 'balanced' cluster with only slight preferences of single
      foods and a 'junk food' cluster. CONCLUSIONS: The simulation study suggests that
      clustering via GMM should be preferred due to its higher flexibility regarding
      cluster volume, shape and orientation. The k-means seems to be a good
      alternative, being easier to use while giving similar results when applied to
      real data.

PMID- 25600127
TI  - Lower Financial Status and Adherence to Medication Determines 10-Year (2004-2014)
      All-Cause Mortality and Risk for Acute Coronary Syndrome Incidence Among Cardiac
      Patients: the GREECS Study.
AB  - BACKGROUND: Financial status has been considered as an important health
      determinant and associated with compliance to healthier lifestyle habits, medical
      treatment and increased prevalence of mental disorders. The aim of this work was
      to evaluate the association between financial status, patient adherence to
      medication, 10-year allcause mortality and risk for Acute Coronary Syndrome
      (ACS), in a Greek sample of cardiac patients. METHODS: From October 2003
      September 2004 a sample of 2,172 consecutive ACS patients from 6 hospitals was
      enrolled. In 2013-14, the 10-year follow-up was performed in 1,918 participants.
      Adherence to medical treatment was recorded through self-reports and financial
      status was classified as low (<9,000?), moderate (9-18,000?), good (19-48,000?)
      and very good (>48,000?). RESULTS: The "low"-to-"very" good financial status 10
      year all-cause mortality rate was 1.7:1 (p<0.001). Unadjusted analysis revealed
      no association between financial status and ACS incidence (p=0.22); however,
      multi-adjusted analysis, after taking into account various clinical and lifestyle
      factors, revealed that "good/very good" financial status was associated with 23%
      (95%CI 2%, 40%, p=0.04) lower 10-year risk of ACS as compared with
      "low/moderate"; a finding that became insignificant when adherence to medication
      was taken into account. CONCLUSIONS: Low financial status seems to play a
      critical role in the long-term ACS prognosis. Health policies, to tackle non
      compliance to medication, are needed to minimize the disease burden in clinical
      and community settings.

PMID- 25600129
TI  - Extracorporeally irradiated clavicle as an autograft in tumour surgery.
AB  - We report the case of a 45-year-old woman who presented with a lump in the mid
      third of the left clavicle, which had recently increased in size to 10 cm in
      diameter. Plain X-ray, computed tomography and bone scans suggested that the lump
      was a parosteal osteosarcoma. Due to the expected 30% functional loss from
      claviculectomy [Wood in The results of total claviculectomy. Clin Orthop Relat
      Res 1986; 207: :186-90.], the patient opted for excision of the tumour plus the
      adjacent clavicle, irradiation and reimplantation of the bone with internal
      fixation. On 2-year follow-up, there was no evidence of recurrence or
      complications, with a good range of movement of the joint. On 4-year follow-up,
      the patient was found to have discomfort, and X-rays showed that the clavicle had
      fractured, which was managed symptomatically. 

PMID- 25600128
TI  - Toxicity reference values for chlorophacinone and their application for assessing
      anticoagulant rodenticide risk to raptors.
AB  - Despite widespread use and benefit, there are growing concerns regarding hazards
      of second-generation anticoagulant rodenticides to non-target wildlife which may
      result in expanded use of first-generation compounds, including chlorophacinone
      (CPN). The toxicity of CPN over a 7-day exposure period was investigated in
      American kestrels (Falco sparverius) fed either rat tissue mechanically-amended
      with CPN, tissue from rats fed Rozol((r)) bait (biologically-incorporated CPN),
      or control diets (tissue from untreated rats or commercial bird of prey diet) ad
      libitum. Nominal CPN concentrations in the formulated diets were 0.15, 0.75 and
      1.5 ug/g food wet weight, and measured concentrations averaged 94 % of target
      values. Kestrel food consumption was similar among groups and body weight varied
      by less than 6 %. Overt signs of intoxication, liver CPN residues, and changes in
      prothrombin time (PT), Russell's viper venom time (RVVT) and hematocrit, were
      generally dose-dependent. Histological evidence of hemorrhage was present at all
      CPN dose levels, and most frequently observed in pectoral muscle and heart. There
      were no apparent differences in toxicity between mechanically-amended and
      biologically-incorporated CPN diet formulations. Dietary-based toxicity reference
      values at which clotting times were prolonged in 50 % of the kestrels were 79.2
      ug CPN consumed/kg body weight-day for PT and 39.1 ug/kg body weight-day for
      RVVT. Based upon daily food consumption of kestrels and previously reported CPN
      concentrations found in small mammals following field baiting trials, these
      toxicity reference values might be exceeded by free-ranging raptors consuming
      such exposed prey. Tissue-based toxicity reference values for coagulopathy in 50
      % of exposed birds were 0.107 ug CPN/g liver wet weight for PT and 0.076 ug/g
      liver for RVVT, and are below the range of residue levels reported in raptor
      mortality incidents attributed to CPN exposure. Sublethal responses associated
      with exposure to environmentally realistic concentrations of CPN could compromise
      survival of free-ranging raptors, and should be considered in weighing the costs
      and benefits of anticoagulant rodenticide use in pest control and eradication
      programs. 

PMID- 25600130
TI  - A case of psychosis induced self-insertion of intracranial hypodermic needles
      causing seizures.
AB  - Self-insertion of foreign bodies is a rare event. This report details a 56-year
      old male who had self-inserted six hypodermic needles into his left frontal lobe
      6 years previously. He subsequently presented with seizures and went on to have
      the needles surgically removed. This represents the first case of its type
      involving hypodermic needles. Given that intracranial needles are a rare finding,
      the management of such patients is complex. Two management issues in particular
      that require consideration are: (i) can the needles be left in situ and (ii) does
      removal of the needles reduce the risk of seizures in the long term? 

PMID- 25600131
TI  - Jejunal diverticula: a rare cause of life-threatening gastrointestinal bleeding.
AB  - Jejunal diverticula are rare and the condition remains mostly asymptomatic.
      However, they can present with vague chronic abdominal symptoms and, in some
      cases, acute life-threatening complications, such as gastrointestinal (GI)
      bleeding, bowel obstruction and perforation. We present a case of an adult male
      who presented with life-threatening GI bleeding secondary to jejunal diverticular
      disease. Whilst there are undoubtedly more common causes of GI bleeding, this
      case demonstrates that jejunal diverticular disease should remain on the
      differential diagnosis and investigations to confirm the diagnosis should be
      considered. However, despite investigations, the diagnosis may remain elusive and
      in patients with on-going bleeding, laparotomy and surgical resection is
      currently the treatment of choice. 

PMID- 25600132
TI  - The reliability of isoinertial force-velocity-power profiling and maximal
      strength assessment in youth.
AB  - The purpose of this study was to quantify the inter-session reliability of force
      velocity-power profiling and estimated maximal strength in youth. Thirty-six
      males (11-15 years old) performed a ballistic supine leg press test at five
      randomized loads (80%, 100%, 120%, 140%, and 160% body mass) on three separate
      occasions. Peak and mean force, power, velocity, and peak displacement were
      collected with a linear position transducer attached to the weight stack. Mean
      values at each load were used to calculate different regression lines and
      estimate maximal strength, force, velocity, and power. All variables were found
      reliable (change in the mean [CIM] = - 1 to 14%; coefficient of variation [CV] =
      3-18%; intraclass correlation coefficient [ICC] = 0.74-0.99), but were likely to
      benefit from a familiarization, apart from the unreliable maximal force/velocity
      ratio (CIM = 0-3%; CV = 23-25%; ICC = 0.35-0.54) and load at maximal power (CIM =
      - 1 to 2%; CV = 10-13%; ICC = 0.26-0.61). Isoinertial force-velocity-power
      profiling and maximal strength in youth can be assessed after a familiarization
      session. Such profiling may provide valuable insight into neuromuscular
      capabilities during growth and maturation and may be used to monitor specific
      training adaptations. 

PMID- 25600133
TI  - Limiting stochastic harm when monitoring diverticular flogosis for lower Hinchey
      classes. Personal proposal for a selection method Reliability Ultrasound Score
      (RUS).
AB  - BACKGROUND: An article in the BMJ issueof May 2012 (11) tackled the issue of
      safeguarding health by preventing diagnostic overtreatment. An observation of the
      diagnostic options in clinical routine enabled us to critically assess the
      appropriateness or notof the use of ionising radiation in monitoring acute
      diverticulitis by means of CT imaging. This disease, which has alwaysbeen
      frequent in elderly patients, has recently assumed a new role as an
      endemicdiseasein the Caucasian populationaged 40 to 50 in the Western world (6).
      MATERIAL AND METHOD: We considered 79 cases coming under observation in the
      Emergency Roomover a period of 115 months, selected from a pool of 136 according
      to Hinchey Score (Hs) 0-1a-1b- assigned on admission after an Ultrasound(US)
      examination . The choice of the first diagnostic approach depended on the
      severity of the patient 's clinical condition, the degree of collaboration of the
      same and the discretion of the radiologist, although the concerted opinion was to
      prefer the US test given its clearly- established advantages of being convenient
      and harmless. During the period of recovery we noted the tendency to subordinate
      the choice of instrument to the habit and discretion of the attending
      practitioner. Our proposal was to introduce a standardised personal criterion
      which took into account the problem of stochastic harm from ionising radiation.
      The need of exposure or not to verify the clinical condition by means of a CT as
      opposed to a US was thus deduced by means of an Reliability Ultrasound Score
      (RUS) RESULTS: Using such score we were able to schedule in 14 out of the 37
      cases in one branch of the study, an effective diagnostic check-up programmein
      safety and with an overall saving of 32 % of the ionising radiation. During this
      study wequantified a total amount of miniSivertnot dispensed, in 79 cases with
      Hs<2deserving of hospital admission. CONCLUSION: This choice moves in the
      direction of safeguarding the patient fromdiagnostic overtreatment,with a
      potential increase in stochastic harm. The application of a reliability
      assessment filterof the US examination is currently in the study phase as regards
      acute diverticular disease in classesHS=/>2 degrees .

PMID- 25600134
TI  - Where is the evidence?

PMID- 25600135
TI  - The relationship between ergosterol and mycotoxin contamination in maize from
      various countries.
AB  - Maize is a good substrate for fungal growth and production of toxic secondary
      metabolites or mycotoxins. The relationships between the fungal biomarker
      ergosterol (ERG) and mycotoxins such as aflatoxins (AFs), ochratoxin A (OTA) and
      zearalenone (ZEA) were investigated in maize collected from four different
      geographic locations. ERG and mycotoxins were measured by high-performance liquid
      chromatography with UV and fluorescence detection. ERG did not correlate with AFs
      in 139 analysed samples. OTA contamination was found in only one sample from the
      North American region. A significant correlation (r (2) = 0.82) was observed
      between ERG and ZEA. AFs and ZEA were found in 47% of all samples. Half of the
      samples contained more than two mycotoxins. Levels of ERG and mycotoxin
      contamination differed by geographical region. North American and Asian samples
      had higher frequencies and levels of ERG and mycotoxin contamination. No AF
      contamination was observed in European samples (limit of detection 0.025 MUg/kg
      for AFB1). We conclude that samples containing less than 3 mg/kg ERG in most
      cases do not exceed the EU maximum limits for AFs, OTA and ZEA.

PMID- 25600136
TI  - Structural and nanomechanical comparison of epitaxially and solution-grown
      amyloid beta25-35 fibrils.
AB  - Abeta25-35, the fibril-forming, biologically active toxic fragment of the full
      length amyloid beta-peptide also forms fibrils on mica by an epitaxial assembly
      mechanism. Here we investigated, by using atomic force microscopy, nanomechanical
      manipulation and FTIR spectroscopy, whether the epitaxially grown fibrils display
      structural and mechanical features similar to the ones evolving under equilibrium
      conditions in bulk solution. Unlike epitaxially grown fibrils, solution-grown
      fibrils displayed a heterogeneous morphology and an apparently helical structure.
      While fibril assembly in solution occurred on a time scale of hours, it appeared
      within a few minutes on mica surface fibrils. Both types of fibrils showed a
      similar plateau-like nanomechanical response characterized by the appearance of
      force staircases. The IR spectra of both fibril types contained an intense peak
      between 1620 and 1640 cm(-1), indicating that beta-sheets dominate their
      structure. A shift in the amide I band towards greater wave numbers in
      epitaxially assembled fibrils suggests that their structure is less compact than
      that of solution-grown fibrils. Thus, equilibrium conditions are required for a
      full structural compaction. Epitaxial Abeta25-35 fibril assembly, while
      significantly accelerated, may trap the fibrils in less compact configurations.
      Considering that under in vivo conditions the assembly of amyloid fibrils is
      influenced by the presence of extracellular matrix components, the ultimate
      fibril structure is likely to be influenced by the features of underlying matrix
      elements.

PMID- 25600137
TI  - Body image investment in breast cancer patients undergoing reconstruction: taking
      a closer look at the Appearance Schemas Inventory-Revised.
AB  - Breast cancer and its treatment can significantly affect a woman's body image. As
      such, it would be useful to understand the importance or value these patients
      place on their appearance. We evaluated the factor structure of the Appearance
      Schemas Inventory-Revised (ASI-R), a measure of body image investment, with a
      sample of 356 breast cancer patients undergoing mastectomy and breast
      reconstruction. Using confirmatory and exploratory factor analyses, we found that
      a three-factor model demonstrated an improvement in fit over the original two
      factor structure of the ASI-R. These factors were named Appearance Self
      Evaluation, Appearance Power/Control, and Appearance Standards and Behavior. The
      three aforementioned factors demonstrated acceptable internal consistency
      reliabilities. Our findings have implications for the use of the ASI-R in an
      oncology setting, specifically for breast cancer patients undergoing
      reconstruction. 

PMID- 25600138
TI  - Sharper graph-theoretical conditions for the stabilization of complex reaction
      networks.
AB  - Across the landscape of all possible chemical reaction networks there is a
      surprising degree of stable behavior, despite what might be substantial
      complexity and nonlinearity in the governing differential equations. At the same
      time there are reaction networks, in particular those that arise in biology, for
      which richer behavior is exhibited. Thus, it is of interest to understand network
      structural features whose presence enforces dull, stable behavior and whose
      absence permits the dynamical richness that might be necessary for life. We
      present conditions on a network's Species-Reaction Graph that ensure a high
      degree of stable behavior, so long as the kinetic rate functions satisfy certain
      weak and natural constraints. These graph-theoretical conditions are considerably
      more incisive than those reported earlier. 

PMID- 25600139
TI  - Cardiovascular effects in rats after intratracheal instillation of metal welding
      particles.
AB  - Studies have indicated that pulmonary exposure to welding fumes can induce a
      series of adverse effects in the respiratory system, including infection,
      bronchitis, siderosis and decreased pulmonary function. Recent clinical and
      epidemiological studies have found that pulmonary exposure to welding fumes is
      also associated with a higher incidence of cardiovascular events. However, there
      is insufficient evidence to confirm a direct effect of welding fumes on the
      cardiovascular system. The present study investigated the effects of pulmonary
      exposure to welding fumes on the heart and the vascular system in rats. Two
      chemically distinct welding fumes generated from manual metal arc-hard surfacing
      (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups
      of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat)
      or saline as control once a week for seven weeks. On days 1 and 7 after the last
      treatment, basal cardiovascular function and the cardiovascular response to
      increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment
      reduced the basal levels of left ventricle end-systolic pressure and dP/dt(max)
      at 1 day post-treatment, and decreased dP/dt(min) in response to isoproterenol
      (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left
      ventricular end-diastolic pressure in response to ISO at 7 days post-treatment.
      Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our
      findings suggest that exposure to different welding fumes can induce different
      adverse effects on the cardiovascular system, and that cardiac contractility may
      be a sensitive indicator of cardiovascular dysfunction.

PMID- 25600140
TI  - Acrolein inhalation alters arterial blood gases and triggers carotid body
      mediated cardiovascular responses in hypertensive rats.
AB  - CONTEXT: Air pollution exposure affects autonomic function, heart rate, blood
      pressure and left ventricular function. While the mechanism for these effects is
      uncertain, several studies have reported that air pollution exposure modifies
      activity of the carotid body, the major organ that senses changes in arterial
      oxygen and carbon dioxide levels, and elicits downstream changes in autonomic
      control and cardiac function. OBJECTIVE: We hypothesized that exposure to
      acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke
      and diesel exhaust, would activate the carotid body chemoreceptor response and
      lead to secondary cardiovascular responses in rats. MATERIALS AND METHODS:
      Spontaneously hypertensive (SH) rats were exposed once for 3 h to 3 ppm acrolein
      gas or filtered air in whole body plethysmograph chambers. To determine if the
      carotid body mediated acrolein-induced cardiovascular responses, rats were
      pretreated with an inhibitor of cystathionine gamma-lyase (CSE), an enzyme
      essential for carotid body signal transduction. RESULTS: Acrolein exposure
      induced several cardiovascular effects. Systolic, diastolic and mean arterial
      blood pressure increased during exposure, while cardiac contractility decreased 1
      day after exposure. The cardiovascular effects were associated with decreases in
      pO2, breathing frequency and expiratory time, and increases in sympathetic tone
      during exposure followed by parasympathetic dominance after exposure. The CSE
      inhibitor prevented the cardiovascular effects of acrolein exposure. DISCUSSION
      AND CONCLUSION: Pretreatment with the CSE inhibitor prevented the cardiovascular
      effects of acrolein, suggesting that the cardiovascular responses with acrolein
      may be mediated by carotid body-triggered changes in autonomic tone. (This
      abstract does not reflect EPA policy.).

PMID- 25600141
TI  - Cellular RNA is chemically modified by exposure to air pollution mixtures.
AB  - RNAs are more susceptible to modifications than DNA, and chemical modifications
      in RNA have an effect on their structure and function. This study aimed to
      characterize chemical effects on total RNA in human A549 lung cells after
      exposure to elevated levels of major secondary air pollutants commonly found in
      urban locations, including ozone (O3), acrolein (ACR) and methacrolein (MACR).
      Enzyme-linked immunosorbent assays (ELISA) were used to measure levels of
      interleukin (IL)-8 in the growth media and 8-oxoguanine (8OG) levels in total
      cellular RNA, and lactate dehydrogenase (LDH) in the growth media was measured by
      a coupled enzymatic assay. Quantitative real-time polymerase chain reaction (qRT
      PCR) was used to measure levels of microRNA 10b (miR-10b). The study found that 1
      h exposure to all tested pollutant mixtures consistently caused significant
      increases in the levels of 8OG in total RNA. In the case of 4 ppm O3 exposures,
      measured levels of IL-8, LDH and miR-10b each showed consistent trends between
      two independent trials, but varied among these three targets. After 1-h exposures
      to an ACR+MACR mixture, measured levels of IL-8, LDH and miR-10b showed variable
      results. For mixtures of O3+ACR+MACR, IL-8 measurements showed no change; miR-10b
      and LDH showed variable results. The results indicate that short-term high
      concentration exposures to air pollution can cause RNA chemical modifications.
      Chemical modifications in RNAs could represent more consistent markers of
      cellular stress relative to other inflammation markers, such as IL-8 and LDH, and
      provide a new biomarker endpoint for mechanistic studies in toxicity of air
      pollution exposure.

PMID- 25600144
TI  - Biomechanical analysis of an aortic aneurysm model and its clinical application
      to thoracic aortic aneurysms for defining "saccular" aneurysms.
AB  - BACKGROUND: We aimed to develop a simple structural model of aortic aneurysms
      using computer-assisted drafting (CAD) in order to create a basis of definition
      for saccular aortic aneurysms. METHODS AND RESULTS: We constructed a simple
      aortic aneurysm model with 2 components: a tube similar to an aorta and an
      ellipse analogous to a bulging aneurysm. Three parameters, including the vertical
      and horizontal diameters of the ellipse and the fillet radius, were altered in
      the model. Using structural analysis with the finite element method, we
      visualized the distribution of the maximum principal stress (MPS) in the aortic
      wall and identified the area(s) of prominent stress. We then selected patients
      with thoracic aortic aneurysms in whom the aneurysm expansion rates were followed
      up and applied the theoretical results to the raw imaging data. The maximum MPS
      drastically increased at areas where the aspect ratio (vertical/horizontal) was
      <1, indicating that "horizontally long" hypothetical ellipses should be defined
      as "saccular" aneurysms. The aneurysm expansion rate for the patients with
      thoracic aneurysms conforming to these parameters was significantly high.
      Further, "vertically long" ellipses with a small fillet might be candidates for
      saccular aneurysms; however, the clinical data did not support this. CONCLUSIONS:
      Based on the biomechanical analysis of a simple aneurysm model and the clinical
      data of the thoracic aortic aneurysms, we defined "horizontally long" aortic
      aneurysms with an aspect ratio of <1 as "saccular" aneurysms.

PMID- 25600142
TI  - Platelet endothelial cell adhesion molecule-1 mediates endothelial-cardiomyocyte
      communication and regulates cardiac function.
AB  - BACKGROUND: Dilated cardiomyopathy is characterized by impaired contractility of
      cardiomyocytes, ventricular chamber dilatation, and systolic dysfunction.
      Although mutations in genes expressed in the cardiomyocyte are the best described
      causes of reduced contractility, the importance of endothelial-cardiomyocyte
      communication for proper cardiac function is increasingly appreciated. In the
      present study, we investigate the role of the endothelial adhesion molecule
      platelet endothelial cell adhesion molecule (PECAM-1) in the regulation of
      cardiac function. METHODS AND RESULTS: Using cell culture and animal models, we
      show that PECAM-1 expressed in endothelial cells (ECs) regulates cardiomyocyte
      contractility and cardiac function via the neuregulin-ErbB signaling pathway.
      Conscious echocardiography revealed left ventricular (LV) chamber dilation and
      systolic dysfunction in PECAM-1(-/-) mice in the absence of histological
      abnormalities or defects in cardiac capillary density. Despite deficits in global
      cardiac function, cardiomyocytes isolated from PECAM-1(-/-) hearts displayed
      normal baseline and isoproterenol-stimulated contractility. Mechanistically,
      absence of PECAM-1 resulted in elevated NO/ROS signaling and NRG-1 release from
      ECs, which resulted in augmented phosphorylation of its receptor ErbB2. Treatment
      of cardiomyocytes with conditioned media from PECAM-1(-/-) ECs resulted in
      enhanced ErbB2 activation, which was normalized by pre-treatment with an NRG-1
      blocking antibody. To determine whether normalization of increased NRG-1 levels
      could correct cardiac function, PECAM-1(-/-) mice were treated with the NRG-1
      blocking antibody. Echocardiography showed that treatment significantly improved
      cardiac function of PECAM-1(-/-) mice, as revealed by increased ejection fraction
      and fractional shortening. CONCLUSIONS: We identify a novel role for PECAM-1 in
      regulating cardiac function via a paracrine NRG1-ErbB pathway. These data
      highlight the importance of tightly regulated cellular communication for proper
      cardiac function.

PMID- 25600145
TI  - Effects of repeated electroejaculations on kinematic sperm subpopulations and
      quality markers of Mexican creole goats.
AB  - Here we show the effects of repeated electroejaculation (EE) on mean values of
      motility, mitochondrial functionality, and expression of active caspases on goat
      sperm obtained by EE. Evaluations were done using CASA and flow cytometry. A
      strategy for identification of kinematic sperm subpopulations, when individual
      data of sperm are not provided by the CASA system, is provided. Fifty semen
      samples, five of each of ten adult creole goats, were obtained by
      electroejaculation. Mean values of total motility, progressive motility and flow
      cytometry evaluations were compared among EEs. Relationships among mean values of
      variables were investigated using Spearman correlation and principal component
      analysis (PCA). For identification of kinematic sperm subpopulations, PCA
      followed by hierarchical clustering was applied on data of the intervals provided
      automatically by the CASA system. Total motility does no change after repeated
      EE. Mean values of motility parameters and molecular markers were unrelated in
      multivariate space, but bivariate correlations were found. Values in upper and
      lower intervals defined clearly the sperm subpopulations, which had motility
      parameters changing over time. Taken together, our results show that repeated EE
      does not affect mean values of total motility, that molecular markers are not
      related with motility parameters, and that it is possible to identify kinematic
      sperm subpopulations when individual data, of motility parameters, are not
      provided by the CASA system. 

PMID- 25600143
TI  - Beat-to-beat spatiotemporal variability in the T vector is associated with sudden
      cardiac death in participants without left ventricular hypertrophy: the
      Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Despite advances in prevention and treatment of cardiovascular
      disease, sudden cardiac death (SCD) remains a clinical challenge. Risk
      stratification in the general population is needed. METHODS AND RESULTS: Beat-to
      beat spatiotemporal variability in the T vector was measured as the mean angle
      between consecutive T-wave vectors (mean TT' angle) on standard 12-lead ECGs in
      14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study.
      Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy,
      ventricular pacing, or QRS duration >=120 ms were excluded. The mean spatial TT'
      angle was 5.21+/-3.55 degrees . During a median of 14 years of follow-up, 235
      SCDs occurred (1.24 per 1000 person-years). After adjustment for demographics,
      coronary heart disease risk factors, and known ECG markers for SCD, mean TT'
      angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to
      1.137; P<0.0001). A mean TT' angle >90th percentile (>9.57 degrees ) was
      associated with a 2-fold increase in the hazard for SCD (hazard ratio 2.01; 95%
      CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T-vector amplitude
      >=0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92;
      95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT' angle
      and age was found: TT' angle was associated with SCD in participants aged <55
      years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in
      participants aged >=55 years (P(interaction)=0.009). CONCLUSIONS: In a large,
      prospective, community-based cohort of left ventricular hypertrophy-free
      participants, increased beat-to-beat spatiotemporal variability in the T vector,
      as assessed by increasing TT' angle, was associated with SCD.

PMID- 25600146
TI  - Breeding period-associated changes in semen quality, concentrations of LH, PRL,
      gonadal steroid and thyroid hormones in domestic goose ganders (Anser anser f.
      domesticus).
AB  - In flocks of geese fertility decreases in the second half of the breeding season.
      The reasons for this reduction in reproduction ability are still unclear. This
      study measured changes in semen quality variables throughout the period of
      intensive breeding in relation to hormonal concentrations associated with the
      sexual activity of ganders. Semen was collected (2*/week) from 2-year-old ganders
      in the period February-June. Standard ejaculation parameters and spermatozoa
      (spz) membrane integrity after E/N and SYBR-14/PI staining were evaluated. The
      DNA Fragmentation Index was measured by flow cytometry and sperm quality factors
      (SQF). The plasma levels of T, E2, P4, LH, PRL, THs in relation to semen
      parameters were evaluated. In ejaculate collected at the onset of the second half
      of breeding (April - spring period), a reduction in sperm concentration and % of
      liveE/N and liveSYBR-14+/PI- spz was shown. At this time, decrease in
      concentrations of LH and T and increase in PRL were found as well as moderate
      changes in THs were observed. However, in May a second peak in T and sperm
      production occurred. The DFI-% was higher in the middle part of breeding. Gonadal
      steroids concentration were not good prognostic marker of the reproductive
      potential of ganders. We suggest that a marked decline in LH and T in the spring
      period indicated the onset of endocrine changes mediated by PRL and THs resulting
      in progressive regression of testis functions. The lowest SQF in the
      spring/summer period coincided with the highest PRL suggesting an anti
      spermatogenic action of PRL in ganders. 

PMID- 25600147
TI  - Origin of the large dispersion of magnetic properties in nanostructured oxides:
      Fe(x)O/Fe3O4 nanoparticles as a case study.
AB  - The intimate relationship between stoichiometry and physicochemical properties in
      transition-metal oxides makes them appealing as tunable materials. These features
      become exacerbated when dealing with nanostructures. However, due to the
      complexity of nanoscale materials, establishing a distinct relationship between
      structure-morphology and functionalities is often complicated. In this regard, in
      the FexO/Fe3O4 system a largely unexplained broad dispersion of magnetic
      properties has been observed. Here we show, thanks to a comprehensive multi
      technique approach, a clear correlation between the magneto-structural properties
      in large (45 nm) and small (9 nm) FexO/Fe3O4 core/shell nanoparticles that can
      explain the spread of magnetic behaviors. The results reveal that while the FexO
      core in the large nanoparticles is antiferromagnetic and has bulk-like
      stoichiometry and unit-cell parameters, the FexO core in the small particles is
      highly non-stoichiometric and strained, displaying no significant
      antiferromagnetism. These results highlight the importance of ample
      characterization to fully understand the properties of nanostructured metal
      oxides. 

PMID- 25600149
TI  - Nicotinamide exerts antioxidative effects on senescent cells.
AB  - Nicotinamide (NAM) has been shown to suppress reactive oxygen species (ROS)
      production in primary human fibroblasts, thereby extending their replicative
      lifespan when added to the medium during long-term cultivation. Based on this
      finding, NAM is hypothesized to affect cellular senescence progression by keeping
      ROS accumulation low. In the current study, we asked whether NAM is indeed able
      to reduce ROS levels and senescence phenotypes in cells undergoing senescence
      progression and those already in senescence. We employed two different cellular
      models: MCF-7 cells undergoing senescence progression and human fibroblasts in a
      state of replicative senescence. In both models, NAM treatment substantially
      decreased ROS levels. In addition, NAM attenuated the expression of the assessed
      senescence phenotypes, excluding irreversible growth arrest. N-acetyl cysteine, a
      potent ROS scavenger, did not have comparable effects in the tested cell types.
      These data show that NAM has potent antioxidative as well as anti-senescent
      effects. Moreover, these findings suggest that NAM can reduce cellular
      deterioration caused by oxidative damage in postmitotic cells in vivo. 

PMID- 25600150
TI  - Regulation of drug transporter expression and function in the placenta.
AB  - INTRODUCTION: Medication of pregnant women is increasingly common in developed
      countries. Several placental drug transporters have been shown to transfer their
      substrates from the trophoblast back to the maternal circulation, thus hindering
      the transplacental passage of xenobiotics and protecting the fetus. However, the
      expression and activity of drug transporter proteins in the placenta vary during
      gestation and are tightly regulated by many factors. In addition, their function
      can be compromised by pathological conditions and/or drug-drug interactions.
      AREAS COVERED: This article reviews current knowledge on placental drug
      transporters, their effects on placental pharmacokinetics and the regulatory
      mechanisms that control their expression and activity. Transcriptional, genetic
      and epigenetic mechanisms of placental transporter regulation and the drug-drug
      interactions that modulate transporter activity are described. Physiological and
      pathological factors that can affect drug transporter expression and function in
      the placenta are also discussed. EXPERT OPINION: The expression and activity of
      drug transporter proteins in the placenta vary during gestation and are tightly
      regulated by many factors. Subsequently, there is a great variability in the
      expression and function of placental drug transporters both within human
      populations (interindividual variability) and also during gestation
      (intraindividual variability). An understanding of the expression and function of
      placental drug transporters is essential for efficient and safe therapy during
      pregnancy. There is clearly a need for further preclinical and clinical studies
      on placental drug transporters, but such investigations must be carefully
      designed and the resulting data should be evaluated with great caution. This
      review highlights several methodological aspects that will have to be considered
      and addressed in order to shed further light on these important issues.

PMID- 25600151
TI  - Acne keloidalis nuchae in Latin American women.

PMID- 25600152
TI  - Churchill: an ultra-fast, deterministic, highly scalable and balanced
      parallelization strategy for the discovery of human genetic variation in clinical
      and population-scale genomics.
AB  - While advances in genome sequencing technology make population-scale genomics a
      possibility, current approaches for analysis of these data rely upon
      parallelization strategies that have limited scalability, complex implementation
      and lack reproducibility. Churchill, a balanced regional parallelization
      strategy, overcomes these challenges, fully automating the multiple steps
      required to go from raw sequencing reads to variant discovery. Through
      implementation of novel deterministic parallelization techniques, Churchill
      allows computationally efficient analysis of a high-depth whole genome sample in
      less than two hours. The method is highly scalable, enabling full analysis of the
      1000 Genomes raw sequence dataset in a week using cloud resources.
      http://churchill.nchri.org/. 

PMID- 25600153
TI  - Altitude effect on birth weight and prematurity in the Province of Catamarca
      (Argentina).
AB  - OBJECTIVES: To analyze the effect of altitude on weight and prematurity at birth
      in the Province of Catamarca (Argentina), between the years 1994 and 2003.
      METHODS: Records of 22,628 newborns were collected from the vital statistics of
      the census of Catamarca. Weight was recategorized to include low birth weight
      (<2,500 g), and gestational age was divided into births that had occurred before
      or after 37 weeks (preterm or at term births). Altitude was also recategorized
      (<1,500 m, 1,500-2,000 m, and > 2,000 m). Nonparametric statistical tests were
      performed. RESULTS: Differences were found in birth weight between sexes and in
      the incidence of low birth weight depending on altitude. This pattern changed
      according to gestational age, because those sexual differences were nonexistent
      or lower in preterm neonates with certain advantages for females. Moreover, it
      was found that the effects of hypoxia were not reflected in birth weight until
      later stages of intrauterine development. CONCLUSIONS: To be female appears to be
      a benefit under conditions of prematurity and high altitude. The increased
      incidence of prematurity due to altitude increase may reflect an adaptive
      advantage of preterm birth under these conditions.

PMID- 25600155
TI  - Detection of main metabolites of XLR-11 and its thermal degradation product in
      human hepatoma HepaRG cells and human urine.
AB  - The metabolism of (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3
      tetramethylcyclopropyl)methanone (XLR-11), a novel synthetic cannabinoid, was
      studied using a HepaRG cell culture. The HepaRG cells were incubated with the
      drug for 48 hours and the metabolites were extracted from the culture medium by
      liquid-liquid extraction. The extract was analyzed by liquid chromatography/mass
      spectrometry to detect the metabolites. N-(5-Hydroxypentyl) metabolite and N
      pentanoic acid metabolite were identified in the culture medium of XLR-11, and
      several other metabolites, presumably formed by oxidation of the first two
      metabolites and XLR-11, were detected. The extract of an XLR-11 user's urine was
      also analyzed; however, the metabolites detected in the urine were different from
      XLR-11 metabolites in the medium. A metabolic experiment with the thermal
      degradation product of XLR-11, XLR-11 degradant, using HepaRG cells revealed that
      the urinary metabolites were almost identical to the XLR-11 degradant
      metabolites. These findings suggest that most of the XLR-11 was degraded by
      heating when the user smoked the herbal product containing XLR-11.

PMID- 25600154
TI  - Baseline working memory activation deficits in dimensional anxious depression as
      detected by magnetoencephalography.
AB  - OBJECTIVE: Anxiety often co-occurs with major depressive disorder (MDD). This
      preliminary study sought to ascertain the extent to which anxious depression
      drives group neurobiological differences between patients with MDD and healthy
      volunteers (HVs). METHODS: Magnetoencephalography beta-band frequency was used to
      compare differences in brain response during the N-back working memory task
      between 30 medication-free patients with treatment-resistant MDD (anxious
      depression=18; nonanxious depression=12) and 28 HVs. RESULTS: Compared to HVs,
      patients with anxious depression had significantly reduced desynchronisation
      (less activation) in the left precuneus, right cuneus, and left insula extending
      into the inferior and middle frontal cortex during the 2-back condition compared
      with the 1-back condition of the N-back working memory task--indicating less
      activation of these neural networks in patients with anxious depression during
      the condition with the highest level of task demands. No other significant group
      differences were found during the working memory conditions. CONCLUSION: This
      preliminary study suggests that a subset of patients--those with anxious
      depression--may be driving observed group differences between patients with MDD
      and HVs. Further neurobiological studies and replication experiments are
      necessary to determine the extent to which this subgroup has preferentially
      influenced our understanding of the underlying neurobiology of depression.

PMID- 25600156
TI  - Induction of a proton gradient across a gold-supported biomimetic membrane by
      electroenzymatic H2 oxidation.
AB  - Energy-transduction mechanisms in living organisms, such as photosynthesis and
      respiration, store light and chemical energy in the form of an electrochemical
      gradient created across a lipid bilayer. Herein we show that the proton
      concentration at an electrode/phospholipid-bilayer interface can be controlled
      and monitored electrochemically by immobilizing a membrane-bound hydrogenase.
      Thus, the energy derived from the electroenzymatic oxidation of H2 can be used to
      generate a proton gradient across the supported biomimetic membrane. 

PMID- 25600157
TI  - Depressive symptoms in Parkinson's disease are related to decreased hippocampus
      and amygdala volume.
AB  - Depression and anxiety are common in Parkinson's disease (PD), and are among the
      non-motor symptoms that interfere with quality of life dramatically. Motor,
      cognitive, and affective features overlap in PD, hampering diagnosis. To shed
      more light on the contribution of structural brain changes to the presence of PD
      related depressive symptoms, we conducted a Voxel-Based Morphometry (VBM) study.
      We hypothesized that depressive symptoms in PD are related to regional gray
      matter (GM) volume loss within the limbic circuit. We analyzed the T1-weigthed
      magnetic resonance imaging (MRI) images of 67 PD patients with a mean disease
      duration of 2.95 (+/-3.39) years. Scores on the Beck Depression Inventory (BDI)
      and GM probability maps were analyzed by regression analysis to study the
      association between GM volume and severity of depressive symptoms. Results are
      reported at both the uncorrected and the family-wise error (FWE) corrected level
      for multiple comparisons. The BDI scores correlated negatively with bilateral
      hippocampus and right amygdala volume and positively with the volume of the
      anterior cingulate cortex. These findings confirm the hypothesized involvement of
      the limbic circuit in PD-related depressive symptoms. We speculate that non
      dopaminergic changes are essential in the pathophysiology of depressive symptoms
      in PD, because our findings suggest the involvement of extra-striatal brain
      regions.

PMID- 25600159
TI  - Conceptualizing the impacts of dual practice on the retention of public sector
      specialists - evidence from South Africa.
AB  - BACKGROUND: 'Dual practice', or multiple job holding, generally involves public
      sector-based health workers taking additional work in the private sector. This
      form of the practice is purported to help retain public health care workers in
      low and middle-income countries' public sectors through additional wage
      incentives. There has been little conceptual or empirical development of the
      relationship between dual practice and retention. METHODS: This article helps
      begin to fill this gap, drawing on empirical evidence from a qualitative study
      focusing on South African specialists. Fifty-one repeat, in-depth interviews were
      carried out with 28 doctors (predominantly specialists) with more than one job,
      in one public and one private urban hospital. RESULTS: Findings suggest dual
      practice can impact both positively and negatively on specialists' intention to
      stay in the public sector. This is through multiple conceptual channels including
      those previously identified in the literature such as dual practice acting as a
      'stepping stone' to private practice by reducing migration costs. Dual practice
      can also lead specialists to re-evaluate how they compare public and private
      jobs, and to overworking which can expedite decisions on whether to stay in the
      public sector or leave. Numerous respondents undertook dual practice without
      official permission. CONCLUSIONS: The idea that dual practice helps retain public
      specialists in South Africa may be overstated. Yet banning the practice may be
      ineffective, given many undertake it without permission in any case. Regulation
      should be better enforced to ensure dual practice is not abused. The conceptual
      framework developed in this article could form a basis for further qualitative
      and quantitative inquiry.

PMID- 25600158
TI  - Role of the Copper(II) Complex Cu[15]pyN5 in Intracellular ROS and Breast Cancer
      Cell Motility and Invasion.
AB  - Multiple mechanisms related to metastases undergo redox regulation. Cu[15]pyN5 is
      a redox-active copper(II) complex previously studied as a chemotherapy sensitizer
      in mammary cells. The effects of a cotreatment with Cu[15]pyN5 and doxorubicin
      (dox) were evaluated in two human breast cancer cell lines: MCF7 (low
      aggressiveness) and MDA-MB-231 (highly aggressive). Cu[15]pyN5 decreased MCF7
      directed cell migration. In addition, a cotreatment with dox and Cu[15]pyN5
      reduced the proteolytic invasion of MDA-MB-231 cells. Cell detachment was not
      affected by exposure to these agents. Cu[15]pyN5 and dox significantly increased
      intracellular ROS in both cell lines. This increase could be at least partially
      due to H2 O2 accumulation. The combination of Cu[15]pyN5 with dox may be
      beneficial in breast cancer treatment as it could help reduce cancer cell
      migration and invasion. Moreover, the ligand [15]pyN5 has a high affinity for
      copper(II) and displays potential anti-angiogenic properties. Overall, we present
      a potential drug that might arrest the progression of breast cancer by different
      and complementary mechanisms. 

PMID- 25600160
TI  - Prediction of escape red blood cell transfusion in expectantly managed women with
      acute anaemia after postpartum haemorrhage.
AB  - OBJECTIVE: To determine clinical predictors of escape red blood cell (RBC)
      transfusion in postpartum anaemic women, initially managed expectantly, and the
      additional predictive value of health-related quality of life (HRQoL) measures.
      DESIGN: Secondary analysis of women after postpartum haemorrhage, either randomly
      allocated to, or opting for expectant management. SETTING: Thirty-seven hospitals
      in the Netherlands. POPULATION: A total of 261 randomised and 362 nonrandomised
      women. METHODS: We developed prediction models to assess the need for RBC
      transfusion: one using clinical variables (model 1), and one extended with scores
      on the HRQoL-measures Multidimensional Fatigue Inventory (MFI) and EuroQol-5D
      (model 2). Model performance was assessed by discrimination and calibration.
      Models were internally validated with bootstrapping techniques to correct for
      overfitting. MAIN OUTCOME MEASURES: Escape RBC transfusion. RESULTS: Seventy-five
      women (12%) received escape RBC transfusion. Independent predictors of escape RBC
      transfusion (model 1) were primiparity, multiple pregnancy, total blood loss
      during delivery and haemoglobin concentration postpartum. Maternal age, body mass
      index, ethnicity, education, medical indication of pregnancy, mode of delivery,
      preterm delivery, placental removal, perineal laceration, Apgar score and
      breastfeeding intention had no predictive value. Addition of HRQoL-scores (model
      2), significantly improved the model's discriminative ability: c-statistics of
      model 1 and 2 were 0.65 (95% CI 0.58-0.72) and 0.72 (95% CI 0.65-0.79),
      respectively. The calibration of both models was good. CONCLUSIONS: In postpartum
      anaemic women, several clinical variables predict the need for escape RBC
      transfusion. Adding HRQoL-scores improves model performance. After external
      validation, the extended model may be an important tool for counselling and
      decision making in clinical practice.

PMID- 25600161
TI  - Quantifying heterogeneity and dynamics of clonal fitness in response to
      perturbation.
AB  - The dynamics of heterogeneous clonal lineages within a cell population, in
      aggregate, shape both normal and pathological biological processes. Studies of
      clonality typically relate the fitness of clones to their relative abundance,
      thus requiring long-term experiments and limiting conclusions about the
      heterogeneity of clonal fitness in response to perturbation. We present, for the
      first time, a method that enables a dynamic, global picture of clonal fitness
      within a mammalian cell population. This novel assay allows facile comparison of
      the structure of clonal fitness in a cell population across many perturbations.
      By utilizing high-throughput imaging, our methodology provides ample statistical
      power to define clonal fitness dynamically and to visualize the structure of
      perturbation-induced clonal fitness within a cell population. We envision that
      this technique will be a powerful tool to investigate heterogeneity in biological
      processes involving cell proliferation, including development and drug response.

PMID- 25600162
TI  - Which is the appropriate adjuvant endocrine therapy for premenopausal patients
      with breast cancer?

PMID- 25600163
TI  - Effect of dietary fat and food consistency on gastroparesis symptoms in patients
      with gastroparesis.
AB  - BACKGROUND: Nutrition therapy for gastroparesis focuses on reducing meal size,
      fiber, fat intake, and increasing liquids intake relative to solid foods.
      Evidence to support these dietary interventions has been anecdotal. The aim of
      this study was to determine the effect of fat intake and solid/liquid meal
      consistency on symptoms in gastroparesis. METHODS: Twelve patients with
      gastroparesis were studied on four separate days receiving one of four meals each
      day in a randomized order: high-fat solid, high-fat liquid, low-fat liquid, and
      low-fat solid meal. At each visit, eight gastrointestinal symptoms were rated
      from 0 (none) to 4 (very severe) every 15 min, before and for 4 h after meal
      ingestion. KEY RESULTS: There was an increase in the total symptom score in the
      following order: high-fat solid > low-fat solid > high-fat liquid > low-fat
      liquid. For the high-fat solid meal, symptoms remained elevated throughout the 4
      h postprandial period. Severity of nausea more than doubled after the high-fat
      solid meal, whereas the low-fat liquid meal caused the least increase in nausea.
      CONCLUSIONS & INFERENCES: A high-fat solid meal significantly increased overall
      symptoms among individuals with gastroparesis, whereas a low-fat liquid meal had
      the least effect. With respect to nausea, low-fat meals were better tolerated
      than high-fat meals, and liquid meals were better tolerated than solid meals.
      These data provide support for recommendations that low-fat and increased liquid
      content meals are best tolerated in patients with symptomatic gastroparesis.

PMID- 25600164
TI  - Chief architect of Obamacare sparks furore over wish to "die at 75".

PMID- 25600165
TI  - Chiral recognition of L-tryptophan with beta-cyclodextrin-modified biomimetic
      single nanochannel.
AB  - A stable system of enantioselectively recognising L-tryptophan based on beta
      cyclodextrin-modified single nanochannel fabricated in a polyimide membrane was
      demonstrated, and we realized the chiral recognition of an essential amino acid
      with this system for the first time.

PMID- 25600166
TI  - Bridging organizational divides in health care: an ecological view of health
      information exchange.
AB  - BACKGROUND: The fragmented nature of health care delivery in the United States
      leads to fragmented health information and impedes patient care continuity and
      safety. Technologies to support interorganizational health information exchange
      (HIE) are becoming more available. Understanding how HIE technology changes
      health care delivery and affects people and organizations is crucial to long-term
      successful implementation. OBJECTIVE: Our study investigated the impacts of HIE
      technology on organizations, health care providers, and patients through a new,
      context-aware perspective, the Regional Health Information Ecology. METHODS: We
      conducted more than 180 hours of direct observation, informal interviews during
      observation, and 9 formal semi-structured interviews. Data collection focused on
      workflow and information flow among health care team members and patients and on
      health care provider use of HIE technology. RESULTS: We structured the data
      analysis around five primary information ecology components: system, locality,
      diversity, keystone species, and coevolution. Our study identified three main
      roles, or keystone species, involved in HIE: information consumers, information
      exchange facilitators, and information repositories. The HIE technology impacted
      patient care by allowing providers direct access to health information, reducing
      time to obtain health information, and increasing provider awareness of patient
      interactions with the health care system. Developing the infrastructure needed to
      support HIE technology also improved connections among information technology
      support groups at different health care organizations. Despite the potential of
      this type of technology to improve continuity of patient care, HIE technology
      adoption by health care providers was limited. CONCLUSIONS: To successfully build
      a HIE network, organizations had to shift perspectives from an ownership view of
      health data to a continuity of care perspective. To successfully integrate
      external health information into clinical work practices, health care providers
      had to move toward understanding potential contributions of external health
      information. Our study provides a foundation for future context-aware development
      and implementation of HIE technology. Integrating concepts from the Regional
      Health Information Ecology into design and implementation may lead to wider
      diffusion and adoption of HIE technology into clinical work.

PMID- 25600167
TI  - Dose-adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal
      failure.
AB  - OBJECTIVE: To determine the potential for arsenic trioxide (ATO) to be safely and
      effectively incorporated into induction therapy of newly diagnosed acute
      promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF)
      by reduction of the ATO dosage to compensate for reduced renal elimination of
      arsenic in CRF. PATIENTS AND METHODS: Two of the four CRF patients with APL in
      the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73
      m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood
      arsenic levels to those in APL patients with normal renal function who achieved
      molecular remission (MR) while receiving 10 mg ATO daily for 28 d. RESULTS:
      Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO
      administered to APL patients with normal renal function. No clinically
      significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative
      MR was achieved after one treatment course in two patients and after two courses
      in the others. Relapse-free survival is 155, 60, 43 and 5 months. CONCLUSION: The
      observations in this pilot study have demonstrated whole-blood arsenic levels can
      provide a guide to adjustments of ATO dosage schedules that permit safe and
      effective therapeutic outcomes in APL patients with severely compromised renal
      function.

PMID- 25600168
TI  - Excision repair cross-complementation group 1 protein expression predicts
      survival in patients with high-grade, non-metastatic osteosarcoma treated with
      neoadjuvant chemotherapy.
AB  - AIMS: To evaluate the clinical impact of excision repair cross-complementation
      group 1 (ERCC1) expression in high-grade osteosarcoma (OS). METHODS AND RESULTS:
      Immunohistochemistry was performed on biopsies from 99 OS patients enrolled in
      the ISG/OS-Oss training set or ISG/SSG1 validation set neoadjuvant chemotherapy
      protocols, based on the use of cisplatin, adriamycin, methotrexate, and
      ifosfamide. In the training set, ERCC1 positivity was found in eight of 31 (26%)
      patients, and was significantly associated with worse event-free survival (EFS)
      (P = 0.042) and overall survival (OVS) (P = 0.001). In the validation set, ERCC1
      positivity was found in 22 of 68 (32%) patients, and its significant associations
      with poorer EFS (P = 0.028) and OVS (P = 0.022) were confirmed. Multivariate
      analyses performed on the whole patient series indicated that ERCC1 positivity
      was the only marker that was significantly associated with a higher risk of worse
      prognosis, in terms of both EFS and OVS (P = 0.013). Co-evaluation of ERCC1 and
      ABCB1 expression showed that patients who were positive for both markers had a
      significantly worse prognosis. CONCLUSIONS: The ERCC1 level at diagnosis is
      predictive for the outcome of patients with non-metastatic, high-grade OS treated
      with neoadjuvant chemotherapy, and co-evaluation with ABCB1 can identify high
      risk groups of OS patients who are refractory to standard regimens.

PMID- 25600170
TI  - Iowa State Fair food finder iPhone application.

PMID- 25600169
TI  - Children with atopic dermatitis show clinical improvement after Lactobacillus
      exposure.
AB  - BACKGROUND: The role of probiotics in the treatment of atopic dermatitis (AD) is
      not clearly established. Further clinical trials with new probiotic formulations
      are warranted. OBJECTIVES: To assess the effects of Lactobacillus paracasei (LP)
      and Lactobacillus fermentum (LF), and their mixture on the disease severity,
      quality of life, and immune biomarkers of children with AD. METHOD: A double
      blind, prospective, randomized placebo-controlled study was conducted on 220
      children aged 1-18 years with moderate-to-severe AD (Trial number: NCT01635738).
      The children were randomized to receive LP, LF, LP + LF mixture, and placebo for
      3 months. Changes in severity scoring of atopic dermatitis (SCORAD), Family
      Dermatology Life Quality Index (FDLQI), and Children's Dermatology Life Quality
      Index (CDLQI) scores in the different groups and at different visits were
      evaluated. Skin prick tests, levels of IgE, IFN-gamma, IL-4, TGF-beta, and TNF
      alpha, and urine biomarkers were also evaluated. RESULTS: Children who received
      LP, LF, and LP + LF mixture showed lower SCORAD scores than the placebo group (P
      < 0.001), and this difference remained even at 4 months after discontinuing the
      probiotics. The FDLQI and CDLQI scores were lower in the LP, LF, and LP + LF
      mixture group than in the placebo group (P = 0.02 and 0.03). IgE, TNF-alpha,
      urine eosinophilic protein X, and 8-OHdG levels decreased, whereas IFN-gamma and
      TGF-beta increased in the probiotic groups, but these did not reach statistical
      significance except for IL-4 (P = 0.04). In subgroup analyses, SCORAD scores
      significantly decreased after probiotic treatment especially in children younger
      than age 12, with breastfeeding > 6 months, and with mite sensitization (P <
      0.001). CONCLUSION: Supplementation of a probiotic mixture of LP and LF is
      associated with clinical improvement in children with AD.

PMID- 25600171
TI  - Nuclear trafficking, histone cleavage and induction of apoptosis by the
      meningococcal App and MspA autotransporters.
AB  - Neisseria meningitidis, a major cause of bacterial meningitis and septicaemia,
      secretes multiple virulence factors, including the adhesion and penetration
      protein (App) and meningococcal serine protease A (MspA). Both are conserved,
      immunogenic, type Va autotransporters harbouring S6-family serine endopeptidase
      domains. Previous work suggested that both could mediate adherence to human
      cells, but their precise contribution to meningococcal pathogenesis was unclear.
      Here, we confirm that App and MspA are in vivo virulence factors since human CD46
      expressing transgenic mice infected with meningococcal mutants lacking App, MspA
      or both had improved survival rates compared with mice infected with wild type.
      Confocal imaging showed that App and MspA were internalized by human cells and
      trafficked to the nucleus. Cross-linking and enzyme-linked immuno assay (ELISA)
      confirmed that mannose receptor (MR), transferrin receptor 1 (TfR1) and histones
      interact with MspA and App. Dendritic cell (DC) uptake could be blocked using
      mannan and transferrin, the specific physiological ligands for MR and TfR1,
      whereas in vitro clipping assays confirmed the ability of both proteins to
      proteolytically cleave the core histone H3. Finally, we show that App and MspA
      induce a dose-dependent increase in DC death via caspase-dependent apoptosis. Our
      data provide novel insights into the roles of App and MspA in meningococcal
      infection. 

PMID- 25600172
TI  - Making big data useful for health care: a summary of the inaugural mit critical
      data conference.
AB  - With growing concerns that big data will only augment the problem of unreliable
      research, the Laboratory of Computational Physiology at the Massachusetts
      Institute of Technology organized the Critical Data Conference in January 2014.
      Thought leaders from academia, government, and industry across disciplines
      including clinical medicine, computer science, public health, informatics,
      biomedical research, health technology, statistics, and epidemiology-gathered and
      discussed the pitfalls and challenges of big data in health care. The key message
      from the conference is that the value of large amounts of data hinges on the
      ability of researchers to share data, methodologies, and findings in an open
      setting. If empirical value is to be from the analysis of retrospective data,
      groups must continuously work together on similar problems to create more
      effective peer review. This will lead to improvement in methodology and quality,
      with each iteration of analysis resulting in more reliability. 

PMID- 25600174
TI  - Oral treatment with the melatonin agonist agomelatine lowers the intraocular
      pressure of glaucoma patients.
AB  - PURPOSE: Agomelatine is an agonist of melatonin that is used in the treatment of
      major depressive disorders. It has also shown an ability to decrease IOP in
      experiment animals and in normal human subjects. This pilot study addresses for
      the first time agomelatine effects on the IOP of patients affected by POAG.
      METHODS: Ten patients affected by hypertensive POAG treated by multiple
      hypotensive topical drugs and under further treatment with agomelatine (25 mg
      day(-1) per os) for psychiatric problems, were enrolled. IOP tonometric values
      were measured at enrolment and after 15 and 30 days of agomelatine
      supplementation. RESULTS: Agomelatine given orally showed a significant
      hypotonising effect, stably decreasing IOP by roughly 30% of the enrolment value
      after 15 and 30 days of treatment. CONCLUSIONS: The hypotonising effect of oral
      systemic agomelatine at 25 mg day(-1) was able to further decrease IOP in both
      eyes of all enrolled POAG patients in which multiple drug treatment with anti
      glaucoma eye drops had no further effect.

PMID- 25600173
TI  - Mapping sites of aspirin-induced acetylations in live cells by quantitative acid
      cleavable activity-based protein profiling (QA-ABPP).
AB  - Target-identification and understanding of mechanism-of-action (MOA) are
      challenging for development of small-molecule probes and their application in
      biology and drug discovery. For example, although aspirin has been widely used
      for more than 100 years, its molecular targets have not been fully characterized.
      To cope with this challenge, we developed a novel technique called quantitative
      acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the
      following two parts: (i) activity-based protein profiling (ABPP) and iTRAQTM
      quantitative proteomics for identification of target proteins and (ii) acid
      cleavable linker-based ABPP for identification of peptides with specific binding
      sites. It is known that reaction of aspirin with its target proteins leads to
      acetylation. We thus applied the above technique using aspirin-based probes in
      human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides
      with exact acetylation sites. By correlating these two sets of data, 523 proteins
      were identified as targets of aspirin. We used various biological assays to
      validate the effects of aspirin on inhibition of protein synthesis and induction
      of autophagy which were elicited from the pathway analysis of Aspirin target
      profile. This technique is widely applicable for target identification in the
      field of drug discovery and biology, especially for the covalent drugs. 

PMID- 25600176
TI  - Read the paper! Re: Cheng/Ho point/counterpoint on electrodiagnostic testing
      before surgery for spinal stenosis.

PMID- 25600175
TI  - Normalisation method can affect gluteus medius electromyography results during
      weight bearing exercises in people with hip osteoarthritis (OA): a case control
      study.
AB  - Surface electromyography (sEMG) is used to assess muscle activation during
      therapeutic exercise, but data are significantly affected by inter-individual
      variability and requires normalisation of the sEMG signal to enable comparison
      between individuals. The purpose of this study was to compare two normalisation
      methods, a maximal method (maximum voluntary isometric contraction (MVIC)) and
      non-maximal peak dynamic method (PDM), on gluteus medius (GMed) activation using
      sEMG during three weight-bearing exercises in people with hip osteoarthritis (OA)
      and healthy controls. Thirteen people with hip OA and 20 controls performed three
      exercises (Squat, Step-Up, Step-Down). Average root-mean squared EMG amplitude
      based on MVIC and PDM normalisation was compared between groups for both involved
      and uninvolved hips using Mann-Whitney tests. Using MVIC normalisation,
      significantly higher normalised GMed EMG amplitudes were found in the OA group
      during all Step-up and down exercises on the involved side (p=0.02-0.001) and
      most of the Step exercises on the uninvolved side (p=0.03-0.04), but not the
      Squat (p>0.05), compared to controls. Using PDM normalisation, significant
      between-group differences occurred only for Ascending Squat (p=0.03) on the
      involved side. MVIC normalisation demonstrated higher inter-trial relative
      reliability (ICCs=0.78-0.99) than PDM (ICCs=0.37-0.84), but poorer absolute
      reliability using Standard Error of Measurement. Normalisation method can
      significantly affect interpretation of EMG amplitudes. Although MVIC-normalised
      amplitudes were more sensitive to differences between groups, there was greater
      variability using this method, which raises concerns regarding validity.
      Interpretation of EMG data is strongly influenced by the normalisation method
      used, and this should be considered when applying EMG results to clinical
      populations.

PMID- 25600177
TI  - Flooding disturbances increase resource availability and productivity but reduce
      stability in diverse plant communities.
AB  - The natural world is increasingly defined by change. Within the next 100 years,
      rising atmospheric CO2 concentrations will continue to increase the frequency and
      magnitude of extreme weather events. Simultaneously, human activities are
      reducing global biodiversity, with current extinction rates at ~1,000 * what they
      were before human domination of Earth's ecosystems. The co-occurrence of these
      trends may be of particular concern, as greater biological diversity could help
      ecosystems resist change during large perturbations. We use data from a 200-year
      flood event to show that when a disturbance is associated with an increase in
      resource availability, the opposite may occur. Flooding was associated with
      increases in productivity and decreases in stability, particularly in the highest
      diversity communities. Our results undermine the utility of the biodiversity
      stability hypothesis during a large number of disturbances where resource
      availability increases. We propose a conceptual framework that can be widely
      applied during natural disturbances.

PMID- 25600178
TI  - Where are the strongest associations between autistic traits and traits of ADHD?
      evidence from a community-based twin study.
AB  - Autism spectrum conditions (ASC) and attention-deficit/hyperactivity disorder
      (ADHD) regularly co-occur. Twin studies increasingly indicate that these
      conditions may have overlapping genetic causes. Less is known about the degree to
      which specific autistic traits relate to specific behaviours characteristic of
      ADHD. We hence tested, using the classical twin design, whether specific
      dimensional autistic traits, including social difficulties, communication
      atypicalities and repetitive behaviours, would display differential degrees of
      aetiological overlap with specific traits of ADHD, including
      hyperactivity/impulsivity and inattention. Parents of approximately 4,000 pairs
      of 12-year-old twins completed the Childhood Autism Spectrum Test and Conners'
      Parent Rating Scale. These measures were divided into subscales corresponding to
      different types of autistic and ADHD behaviours. Twin model fitting suggested
      that the degree of genetic overlap was particularly strong between communication
      difficulties and traits of ADHD (genetic correlations = .47-.51), while
      repetitive behaviours and social difficulties showed moderate (genetic
      correlations = .12-.33) and modest (.05-.11) genetic overlap respectively.
      Environmental overlap was low across all subscales (correlations = .01-.23).
      These patterns were also apparent at the extremes of the general population, with
      communication difficulties showing the highest genetic overlap with traits of
      ADHD. These findings indicate that molecular genetic studies seeking to uncover
      the shared genetic basis of ASC and ADHD would benefit from taking a symptom
      specific approach. Furthermore, they could also help to explain why studies of
      the communication abilities of individuals with ASC and ADHD have produced
      overlapping findings. 

PMID- 25600179
TI  - Type A iatrogenic aortic dissection following catheterization without coronary
      involvement: long-term prognosis.

PMID- 25600181
TI  - School children learn BLS better and in less time than adults.

PMID- 25600180
TI  - Greater adherence to a Mediterranean dietary pattern is associated with improved
      plasma lipid profile: the Aragon Health Workers Study cohort.
AB  - INTRODUCTION AND OBJECTIVES: There is wide recognition of the importance of
      healthy eating in cardiovascular health promotion. The purpose of this study was
      to identify the main dietary patterns among a Spanish population, and to
      determine their relationship with plasma lipid profiles. METHODS: A cross
      sectional analysis was conducted of data from 1290 participants of the Aragon
      Workers Health Study cohort. Standardized protocols were used to collect clinical
      and biochemistry data. Diet was assessed through a food frequency questionnaire,
      quantifying habitual intake over the past 12 months. The main dietary patterns
      were identified by factor analysis. The association between adherence to dietary
      patterns and plasma lipid levels was assessed by linear and logistic regression.
      RESULTS: Two dietary patterns were identified: a Mediterranean dietary pattern,
      high in vegetables, fruits, fish, white meat, nuts, and olive oil, and a Western
      dietary pattern, high in red meat, fast food, dairy, and cereals. Compared with
      the participants in the lowest quintile of adherence to the Western dietary
      pattern, those in the highest quintile had 4.6 mg/dL lower high-density
      lipoprotein cholesterol levels (P < .001), 8 mg/dL lower apolipoprotein A1 levels
      (P = .005) and a greater risk of having decreased high-density lipoprotein
      cholesterol (odds ratio = 3.19; 95% confidence interval, 1.36-7.5; P-trend =
      .03). Participants adhering to the Mediterranean dietary pattern had 3.3mg/dL
      higher high-density lipoprotein cholesterol levels (P < .001), and a ratio of
      triglycerides to high-density lipoprotein cholesterol that was 0.43 times lower
      (P = .043). CONCLUSIONS: Adherence to the Mediterranean dietary pattern is
      associated with improved lipid profile compared with a Western dietary pattern,
      which was associated with a lower odds of optimal high-density lipoprotein
      cholesterol levels in this population.

PMID- 25600182
TI  - Evaluation of glucose management during therapeutic hypothermia at a Tertiary
      Academic Medical Center.
AB  - STUDY AIM: Alterations in metabolic function during therapeutic hypothermia (TH)
      decrease responsiveness to insulin and increase the risk of hyperglycemia.
      Glycemic control is associated with improved outcomes in selected patients;
      however, glycemic management strategies during TH are not defined. The objective
      of this analysis was to evaluate the glycemic metrics and IV insulin
      administration in critically ill patients during the cooling and rewarming phases
      of TH. METHODS: Data from 37 patients who received at least 6h of therapeutic
      hypothermia for cardiac arrest between January 2007 and January 2010 were
      retrospectively evaluated, 14 (37.8%) of whom had diabetes. RESULTS: The mean
      blood glucose was 9.16+/-3.22mmol/L and 6.54+/-2.45mmol/L; p<0.01 during cooling
      and rewarming, respectively. Twelve (32.4%) patients experienced at least one
      hypoglycemic event, defined as a blood glucose <4mmol/L. Nineteen (51.4%)
      patients experienced at least one hyperglycemic event, defined as a blood glucose
      >11.11mmol/L and 15 (40.5%) patients received IV insulin therapy. Patients on IV
      insulin had a higher incidence of diabetes (9 vs. 5; p<0.05), higher admission
      blood glucose (13.89+/-6.13 vs. 11.03+/-4.65mmol/L; p=0.11), and a higher
      incidence of hyperglycemia (14 vs. 2; p<0.01) and hypoglycemia (8 vs. 4; p<0.05).
      Of the patients on IV insulin, mean insulin requirements during cooling and
      rewarming were 15.2+/-16.1 and 7+/-12.5units/h, respectively. CONCLUSION: TH is
      commonly associated with hyperglycemia, hypoglycemia, and the use of IV insulin
      therapy. Further research is needed to determine optimal glycemic management
      strategies to prevent hyper- and hypoglycemia in patients during the different
      phases of TH.

PMID- 25600183
TI  - Association between early arterial blood gas tensions and neurological outcome in
      adult patients following in-hospital cardiac arrest.
AB  - OBJECTIVE: The early partial pressures of arterial O2 (PaO2) and CO2 (PaCO2) have
      been found in animal studies to be correlated with neurological outcome after
      brain injury. However, the relationship of early PaO2 and PaCO2 to the
      neurological outcomes of resuscitated patients after cardiac arrest was still not
      clear. METHODS: This was a retrospective observational cohort study in a single
      medical center. Adult patients who had in-hospital cardiac arrest between 2006
      and 2012 and achieved sustained return of spontaneous circulation (ROSC)
      (ROSC>20min without resumption of chest compression) were included. Multivariable
      logistic regression analysis was used to identify factors associated with
      favorable neurological outcome at hospital discharge. The first PaO2 and PaCO2
      values measured after first sustained ROSC were used for analysis. RESULTS: Of
      the 550 included patients, 154 (28%) survived to hospital discharge and 74
      (13.5%) achieved favorable neurological outcome. The mean time from sustained
      ROSC to the measurement of PaO2 and PaCO2 was 136.8min. The mean PaO2 and PaCO2
      were 167.4mmHg and 40.3mmHg, respectively. PaO2 between 70 and 240mmHg (odds
      ratio [OR] 1.96, 95% confidence interval [CI] 1.08-3.64) and PaCO2 levels (OR
      0.98, 95% CI 0.95-0.99) were positively and inversely associated with favorable
      neurological outcome, respectively. CONCLUSIONS: The early PaO2 and PaCO2 levels
      obtained after ROSC might be correlated with neurological outcome of patients
      with in-hospital cardiac arrest. However, because of the inherent limitations of
      the retrospective design, these results should be further validated in future
      studies.

PMID- 25600184
TI  - Frequency of primary cutaneous lymphoma variants in Austria: retrospective data
      from a dermatology referral centre between 2006 and 2013.
AB  - BACKGROUND: Primary cutaneous lymphomas (PCL) are a heterogenous group of rare
      lymphoid neoplasms with incomplete information on global and regional prevalence.
      The recently introduced lymphoma classifications define distinctive
      clinicopathological disease entities that should allow for more accurate
      epidemiological assessment. OBJECTIVE: The aim of this study was to evaluate the
      prevalence and clinical spectrum of PCL diagnosed and treated at the Department
      of Dermatology and Venereology in St. Polten, Lower Austria, a dermatology
      referral centre providing secondary and tertiary care for a population of about
      600 000. METHODS: In this retrospective study pathology reports, electronically
      archived between 2006 and 2013, were screened for the terms lymphoma, mycosis
      fungoides (MF) and lymphomatoid papulosis (LyP). Patients were diagnosed
      according to the current WHO-EORTC classification for cutaneous lymphomas and
      results were compared with data from European, US and Asian centres. RESULTS:
      Among 86 patients with PCL (age 58.3 +/- 17.35 years, mean +/- SD; women 38%, n =
      33; men 62%, n = 53) 83% (n = 71) were classified as cutaneous T-cell lymphomas
      (CTCL) and 17% (n = 15) as cutaneous B-cell lymphomas (CBCL). Nine patients with
      CTCL showed associated haematological disorders and malignomas. Among 47 MF
      patients following variants were observed: pilotropic MF (n = 2), follicular
      mucinosis (n = 1), unilesional MF (n = 1), large-cell transformation (n = 3),
      erythrodermic MF (n = 1), poikilodermatous MF (n = 2) and posttransplant
      lymphoproliferative disorder (CD8(+) MF with gamma/delta phenotype after renal
      transplantation) (n = 1). One patient had MF concurrent with lymphomatoid
      papulosis. The group of CBCL comprised six cases (40%) of PCMZL and PCFCL each,
      20% (n = 3) were classified as PCLBCL, LT. CONCLUSION: This study for the first
      time provides data on the distribution of PCL clinicopathologic variants and
      stages according to the latest classification and staging systems in an Austrian
      referral centre.

PMID- 25600185
TI  - High impedance droplet-solid interface lipid bilayer membranes.
AB  - A droplet-solid interface lipid bilayer membrane (DSLM) with high impedance was
      developed through controlling the contact area between an aqueous droplet and
      electrode. The electrode size can be easily controlled from millimeter to
      micrometer level. The droplet-solid interface lipid bilayer membranes were
      characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy
      (EIS), and fluorescence microscopy. The fluorescence recovery after
      photobleaching (FRAP) was applied to determine the diffusion coefficient of egg
      PC DSLM to be 2.58 MUm(2) s(-1). The DSLM resistance can reach up to 26.3 GOmega,
      which was then used to study the ion channel behavior of melittin. The
      resistivity of the bilayer membrane decreased linearly with the increase of
      melittin concentration in the membrane. The high impedance and fluidity of DSLM
      makes it an ideal model cell membrane system for ion channel study and high
      throughput drug screening. 

PMID- 25600186
TI  - Activity of enzalutamide in men with metastatic castration-resistant prostate
      cancer is affected by prior treatment with abiraterone and/or docetaxel.
AB  - BACKGROUND: Enzalutamide and abiraterone are new androgen-axis disrupting
      treatments for metastatic castration-resistant prostate cancer (mCRPC). We
      examined the response and outcomes of enzalutamide-treated mCRPC patients in the
      real-world context of prior treatments of abiraterone and/or docetaxel. METHODS:
      We conducted a seven-institution retrospective study of mCRPC patients treated
      with enzalutamide between January 2009 and February 2014. We compared the
      baseline characteristics, PSA declines, PSA progression-free survival (PSA-PFS),
      duration on enzalutamide and overall survival (OS) across subgroups defined by
      prior abiraterone and/or docetaxel. RESULTS: Of 310 patients who received
      enzalutamide, 36 (12%) received neither prior abiraterone nor prior docetaxel, 79
      (25%) received prior abiraterone, 30 (10%) received prior docetaxel and 165 (53%)
      received both prior abiraterone and prior docetaxel. Within these groups,
      respectively, ?30% PSA decline was achieved among 67, 28, 43 and 24% of patients;
      PSA-PFS was 5.5 (95% CI 4.2-9.1), 4.0 (3.2-4.8), 4.1 (2.9-5.4) and 2.8 (2.5-3.2)
      months; median duration of enzalutamide was 9.1 (7.3-not reached), 4.7 (3.7-7.7),
      5.4 (3.8-8.4) and 3.9 (3.0-4.6) months. Median OS was reached only for the
      patients who received both prior abiraterone and docetaxel and was 12.2 months
      (95% CI 10.7-16.5). 12-month OS was 78% (59-100%), 64% (45-90%), 77% (61-97%) and
      51% (41-62%). Of 70 patients who failed to achieve any PSA decline on prior
      abiraterone, 19 (27%) achieved ?30% PSA decline with subsequent enzalutamide.
      CONCLUSIONS: The activity of enzalutamide is blunted after abiraterone, after
      docetaxel, and still more after both, suggesting subsets of overlapping and
      distinct mechanisms of resistance.

PMID- 25600187
TI  - Apical invasion of intestinal epithelial cells by Salmonella typhimurium requires
      villin to remodel the brush border actin cytoskeleton.
AB  - Salmonella invasion of intestinal epithelial cells requires extensive, though
      transient, actin modifications at the site of bacterial entry. The actin
      modifying protein villin is present in the brush border where it participates in
      the constitution of microvilli and in epithelial restitution after damage through
      its actin-severing activity. We investigated a possible role for villin in
      Salmonella invasion. The absence of villin, which is normally located at the
      bacterial entry site, leads to a decrease in Salmonella invasion. Villin is
      necessary for early membrane-associated processes and for optimal ruffle assembly
      by balancing the steady-state level of actin. The severing activity of villin is
      important for Salmonella invasion in vivo. The bacterial phosphatase SptP tightly
      regulates villin phosphorylation, while the actin-binding effector SipA protects
      F-actin and counterbalances villin-severing activity. Thus, villin plays an
      important role in establishing the balance between actin polymerization and actin
      severing to facilitate the initial steps of Salmonella entry. 

PMID- 25600188
TI  - The association between ICU level of care and mortality in the Netherlands.
AB  - PURPOSE: The relationship between the number of patients admitted to an intensive
      care unit (ICU) volume and mortality is currently the subject of debate. After
      implementation of a national guideline in 2006, all Dutch ICUs have been
      classified into three levels based on ICU size, patient volume, ventilation days,
      and staffing. The goal of this study is to investigate the association between
      ICU level and mortality of ICU patients in the Netherlands. METHODS: We analyzed
      data from 132,159 patients admitted to 87 ICUs between January 1, 2009 and
      October 1, 2011. Logistic GEE analyses were performed to assess the influence of
      ICU level on in-hospital mortality and 90-day mortality in the total ICU
      population and in different ICU subgroups while adjusting for severity of illness
      by APACHE IV. RESULTS: No significant differences were found in the adjusted in
      hospital mortality of the total ICU population and in different subgroups
      admitted to level 1, 2 and 3 ICUs. In-hospital mortality in level 2 and 3 ICUs as
      opposed to level 1 ICUs was 1.06 (0.93-1.22) and 1.10 (0.94-1.29), respectively,
      and 90-day mortality was 0.92 (0.80-1.06) and 1.01 (0.88-1.17). CONCLUSION: We
      demonstrated that ICU level was not associated with significant differences in
      the case-mix adjusted in-hospital and long-term mortality of ICU patients. This
      finding is in contrast with some earlier studies suggesting a volume-outcome
      relationship. Our results may be explained by the successful implementation of
      nationwide mandatory quality requirements and adequate staffing in all three
      levels of ICUs over the last years.

PMID- 25600189
TI  - Obstructive nephropathy presenting as seizures.

PMID- 25600190
TI  - Understanding organ dysfunction in thrombotic thrombocytopenic purpura.

PMID- 25600191
TI  - Diaphragmatic dysfunction at admission in intensive care unit: the value of
      diaphragmatic ultrasonography.

PMID- 25600192
TI  - Increased serum bicarbonate in critically ill patients: a retrospective analysis.
AB  - PURPOSE: Although metabolic alkalosis is a common occurrence, no study has
      evaluated its prevalence, associated factors or outcomes in critically ill
      patients. METHODS: This is a retrospective study from the Multiparameter
      Intelligent Monitoring in Intensive Care II database. From 23,529 adult patient
      records, 18,982 patients met the inclusion criteria. RESULTS: Serum bicarbonate
      levels demonstrated a U-shaped association with mortality with knots at 25 and 30
      mEq/l. Of the total included patients, 5,565 (29.3 %) had at least one serum
      bicarbonate level measurement >30 mEq/l. The majority were exposed to multiple
      factors that are classically associated with metabolic alkalosis (mainly diuretic
      use, hypernatremia, hypokalemia and high gastric output). Patients with increased
      serum bicarbonate exhibited increased ICU LOS, more days on mechanical
      ventilation and higher hospital mortality. After multivariate adjustment, each 5
      mEq/l increment in the serum bicarbonate level above 30 mEq/l was associated with
      an odds ratio of 1.21 for hospital mortality. The association between increased
      serum bicarbonate levels and mortality occurs independently of its possible
      etiologies. CONCLUSION: An increased serum bicarbonate level is common in
      critically ill patients; this can be attributed to multiple factors in the
      majority of cases, and its presence and duration negatively influence patient
      outcomes.

PMID- 25600193
TI  - Empirical studies on usability of mHealth apps: a systematic literature review.
AB  - The release of smartphones and tablets, which offer more advanced communication
      and computing capabilities, has led to the strong emergence of mHealth on the
      market. mHealth systems are being used to improve patients' lives and their
      health, in addition to facilitating communication between doctors and patients.
      Researchers are now proposing mHealth applications for many health conditions
      such as dementia, autism, dysarthria, Parkinson's disease, and so on. Usability
      becomes a key factor in the adoption of these applications, which are often used
      by people who have problems when using mobile devices and who have a limited
      experience of technology. The aim of this paper is to investigate the empirical
      usability evaluation processes described in a total of 22 selected studies
      related to mHealth applications by means of a Systematic Literature Review. Our
      results show that the empirical evaluation methods employed as regards usability
      could be improved by the adoption of automated mechanisms. The evaluation
      processes should also be revised to combine more than one method. This paper will
      help researchers and developers to create more usable applications. Our study
      demonstrates the importance of adapting health applications to users' need. 

PMID- 25600194
TI  - Erratum to: An Enhanced Security Solution for Electronic Medical Records Based on
      AES Hybrid Technique with SOAP/XML and SHA-1.

PMID- 25600195
TI  - Tendon rupture of the flexor digitorum profundus of the little finger secondary
      to hamate non-union.
AB  - Several cases of hamate fracture and non-union have been reported. The hook of
      the hamate acts as a pulley for the flexor tendons for the little and ring
      fingers. Hamate non-union is frequently associated with irritation of the
      adjacent soft tissues. We report the case of hamate non-union that was only
      detected because of a flexor digitorum profundus tendon rupture in the little
      finger, associated with tendinopathy of both flexor tendons of the ring finger. 

PMID- 25600196
TI  - Arterial lactate levels in an emergency department are associated with mortality:
      a prospective observational cohort study.
AB  - OBJECTIVES: Lactate measurements are routinely carried out in emergency
      departments and are associated with increased mortality in septic patients.
      However, no definitive research has been carried out into whether lactate
      measurements can be used as a prognostic marker in a clinically unwell population
      in the emergency department. METHODS: We carried out a prospective observational
      cohort study in consecutive patients whose arterial lactate concentration was
      measured in the emergency department of a tertiary referral hospital assessing
      110,000 patients per year between 11th May and 11th August 2011. The main outcome
      measure was 30-day mortality. RESULTS: There were 120 deaths (16.1%) at 30 days
      postattendance in our cohort of 747 patients. Multivariate logistic regression
      revealed lower lactate levels were associated with 30-day survival: ORs for 30
      day death compared with lactate >=4 were 0.125 (95% CI 0.068 to 0.229) for
      lactate <2 and 0.273 (95% CI 0.140 to 0.533) for lactate 2-<4. Kaplan-Meier
      analysis showed a survival difference when dividing lactate concentrations into
      strata (p<0.0001). This survival difference was maintained when septic diagnoses
      were taken into account. CONCLUSIONS: A single arterial lactate measurement on
      presentation to the emergency department predicts 30-day mortality independent of
      other measures of illness severity.

PMID- 25600197
TI  - Long-term outcomes on lens clarity after lens-sparing vitrectomy for retinopathy
      of prematurity.
AB  - OBJECTIVE: To describe the long-term effect of lens-sparing vitrectomy surgery
      for advanced retinopathy of prematurity (ROP) on lens clarity. DESIGN:
      Retrospective case series at a single tertiary referral pediatric vitreoretinal
      practice. PARTICIPANTS: Four hundred ninety-six eyes from 351 patients were
      included. METHODS: A retrospective chart review was conducted of patients with
      diagnosis of ROP stage 4A, 4B, and 5 who underwent lens-sparing vitrectomy (LSV)
      between 1992 and 2013. Data were collected from patient charts, including gender,
      date of birth, gestational age at birth, birthweight, stage of ROP at
      presentation, initial treatment (laser or cryotherapy), date of LSV, date of
      lensectomy (if performed), lens status at time of lensectomy, date of last visit,
      lens status at last visit, subsequent retinal surgeries, and retinal attachment
      status at last visit. Patients were excluded if any surgery had been performed at
      an outside institution before referral, or if a scleral buckle had been placed.
      Eyes with a concurrent anatomic abnormality, such as coloboma or microcornea, or
      a known family history of familial exudative vitreoretinopathy (FEVR), were also
      excluded. MAIN OUTCOME MEASURES: Retinal reattachment after LSV, lensectomy after
      LSV, lens opacity at the time of lensectomy, and lens clarity at last follow-up.
      RESULTS: Four hundred ninety-six eyes from 351 patients met inclusion criteria
      for this study. The reattachment rate after a single LSV surgery was 82.1% for
      stage 4A, 69.5% for stage 4B, and 42.6% for stage 5. Subsequent retinal surgeries
      were required in 19.8% of eyes, with 88.7% of them including a lensectomy. Among
      eyes requiring lensectomy, 75% occurred within the first year after LSV surgery.
      Lens opacities were present in 26.6% of eyes at the time of lensectomy. Of all
      eyes in this series, 5.9% required lensectomy because of lens opacity.
      CONCLUSIONS: This study demonstrates that lens clarity is observed in most eyes
      after LSV surgery for advanced ROP for the patient's childhood. Within the first
      decade of life, if necessary, lensectomy after LSV occurred mostly within 1 year
      following LSV.

PMID- 25600198
TI  - Postinjection endophthalmitis in the comparison of age-related macular
      degeneration treatments trials (CATT).
AB  - OBJECTIVE: To describe the incidence and outcomes of endophthalmitis after
      intravitreal injections of anti-vascular endothelial growth factor agents in the
      Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and to
      assess the effect of prophylactic topical antimicrobials on incidence. DESIGN:
      Cohort study within a randomized clinical trial. PARTICIPANTS: Patients enrolled
      in CATT. METHODS: Patients with neovascular age-related macular degeneration
      received intravitreal injections of ranibizumab or bevacizumab under 1 of 3
      dosing regimens. The study protocol specified preinjection preparation to include
      use of a sterile lid speculum and povidone iodine (5%). Use of preinjection and
      postinjection antibiotics was at the discretion of the treating ophthalmologist.
      Patients were followed up monthly for 2 years. MAIN OUTCOME MEASURES: Development
      of endophthalmitis and visual acuity. RESULTS: Endophthalmitis developed after 11
      of 18 509 injections (1 per 1700 [0.06%]; 95% confidence interval, 0.03%-0.11%),
      and in 11 of 1185 patients (0.93%; 95% confidence interval, 0.52-1.66). Incidence
      of endophthalmitis was 0.15% among injections with no antibiotic use, 0.08% among
      injections with preinjection antibiotics only, 0.06% among injections with
      postinjection antibiotics only, and 0.04% among injections with preinjection and
      postinjection antibiotics (P = 0.20). All eyes were treated with intravitreal
      antibiotics and 4 underwent vitrectomy. Among the 11 affected eyes, the final
      study visual acuity was 20/40 or better in 4 eyes (36%), 20/50 to 20/80 in 2 eyes
      (18%), 20/100 to 20/160 in 3 eyes (27%), and worse than 20/800 in 2 eyes (18%).
      The final visual acuity was within 2 lines of the visual acuity before
      endophthalmitis in 5 eyes (45%). CONCLUSIONS: Rates of endophthalmitis were low
      and similar to those in other large-scale studies. Use of topical antibiotics
      either before or after injection does not seem to reduce the risk for
      endophthalmitis.

PMID- 25600200
TI  - Microbial keratitis in los angeles: the doheny eye institute and the los angeles
      county hospital experience.
AB  - OBJECTIVE: To evaluate the spectrum and antibiotic susceptibility panel of
      infectious keratitis at a major tertiary care referral eye center and a major
      county hospital in Southern California. DESIGN: Retrospective case series.
      PARTICIPANTS: All cultured infectious keratitis cases from July 1, 2008, through
      December 31, 2012, from the Doheny Eye Institute (DEI) and the Los Angeles County
      + University of Southern California Medical Center (LAC+USC) were evaluated.
      METHODS: Microbiology records were reviewed retrospectively. MAIN OUTCOME
      MEASURES: Microbial isolates as well as antibiotic susceptibility patterns were
      analyzed. RESULTS: One hundred eighty-four (63%) of 290 cases showed positive
      culture results at DEI and 152 (82%) of 186 cases showed positive culture results
      at LAC+USC. Gram-positive pathogens were found to be the most common at both DEI
      (70%) and LAC+USC (68%), with coagulase-negative Staphylococcus being the most
      common gram-positive organism (58% at DEI and 44% at LAC+USC). Pseudomonas
      aeruginosa was the most common gram-negative organism (57% at DEI and 43% at
      LAC+USC). Ciprofloxacin and levofloxacin susceptibility for all tested pathogens
      was 73% at DEI and 81% at LAC+USC (P = 0.16). Oxacillin-resistant Staphylococcus
      aureus (ORSA) was found in 42% of cases at DEI and in 45% of cases at LAC+USC (P
      = 1.00). CONCLUSIONS: There is no significant difference in the spectrum of
      pathogens or antibiotic susceptibility of pathogens at DEI versus LAC+USC, and
      ORSA was found in approximately half of all S. aureus samples.

PMID- 25600199
TI  - Incidence and long-term outcomes of the human immunodeficiency virus neuroretinal
      disorder in patients with AIDS.
AB  - PURPOSE: Patients with AIDS have an abnormality of retina/optic nerve function,
      manifested as decreased contrast sensitivity (in the absence of ocular
      opportunistic infections or media opacity), abnormalities on automated perimetry,
      and loss of retinal nerve fiber layer, even among those with good visual acuity,
      termed the "human immunodeficiency virus (HIV) neuroretinal disorder." The
      objectives of this study were to determine the prevalence, incidence, risk
      factors, and outcomes of HIV neuroretinal disorder. DESIGN: Prospective cohort
      study. PARTICIPANTS: A total of 1822 patients with AIDS without ocular infections
      or media opacities. METHODS: Patients with HIV neuroretinal disorder were
      identified by a contrast sensitivity <1.50 log units in either eye in the absence
      of ocular opportunistic infections or media opacity. MAIN OUTCOME MEASURES:
      Incidence of HIV neuroretinal disorder, mortality, visual impairment (visual
      acuity <=20/50), and blindness (<=20/200) on logarithmic visual acuity charts.
      RESULTS: Sixteen percent of participants had HIV neuroretinal disorder at
      enrollment. The estimated cumulative incidence by 20 years after AIDS diagnosis
      was 51% (95% confidence interval [CI], 46-55). Human immunodeficiency virus
      neuroretinal disorder was more common in women and African Americans. Risk
      factors for HIV neuroretinal disorder included hepatitis C infection, low CD4+ T
      cells, and detectable HIV RNA in the blood. Patients with HIV neuroretinal
      disorder had a 70% excess mortality versus those without it, even after adjusting
      for CD4+ T cells and HIV load (hazard ratio [HR], 1.7; 95% CI, 1.3-2.1; P <
      0.0001). Patients with HIV neuroretinal disorder had increased risks of bilateral
      visual impairment (HR, 6.5; 95% CI, 2.6-10.6; P < 0.0001) and blindness (HR, 5.9;
      95% CI, 2.8-13.7; P = 0.01) versus those without HIV neuroretinal disorder.
      CONCLUSIONS: Human immunodeficiency virus neuroretinal disorder is a common
      finding among patients with AIDS, and it is associated with an increased
      mortality and an increased risk of visual impairment. Successful antiretroviral
      therapy decreases but does not eliminate the risk of HIV neuroretinal disorder.

PMID- 25600202
TI  - A Modified Procedure for Estimating the Impact of the Uptake on the Overall
      Biliary Clearance in Sandwich Culture of Rat Hepatocytes.
AB  - Sandwich culture of hepatocytes is commonly applied for the prediction of in vivo
      biliary clearance (CLbil). In this paper, we present a modified procedure for the
      determination of in vitro CLbil in sandwich culture of rat hepatocytes, which
      allows the estimation of the impact of uptake processes on the overall CLbil. The
      main point of this modification is the separation of uptake and efflux processes.
      Ten drugs from four biopharmaceutics drug disposition classification system
      classes were chosen in order to demonstrate the advantages of this method: 1) the
      uptake is performed identically before the canaliculi are opened, thus the efflux
      starts at the same intracellular concentration of the drugs and the effect of
      Ca2+/Mg2+ depletion on the uptake is excluded; 2) exact intracellular
      concentrations can be measured at the start and at the end of the efflux; 3) the
      biliary clearance can be determined irrespective of the uptake; 4) the
      canalicular and the sinusoidal transport can be measured simultaneously; 5) drug
      drug interactions concerning uptake and efflux transporters can be estimated
      independently. Depending on the degree of uptake, CLbil,app (calculated using the
      concentration of drugs in the medium) was significantly higher (sulfasalazine,
      fluvastatin, rosuvastatin, atorvastatin) or lower (pravastatin, procainamide)
      than CLbil,int (calculated using the intracellular concentration of drugs). When
      the uptake had no impact on the CLbil, the apparent and intrinsic CLbil did not
      differ significantly (lovastatin, rifampicin, quetiapine). Our results confirm
      that transporters may play a significant role in the uptake of drugs both with
      high and poor permeability and solubility.

PMID- 25600201
TI  - In Vitro Evaluation of Reversible and Time-Dependent Inhibitory Effects of
      Kalanchoe crenata on CYP2C19 and CYP3A4 Activities.
AB  - Kalanchoe crenata popularly known as "dog's liver" is used in most African
      countries for the treatment of chronic diseases such as diabetes, asthma and
      HIV/AIDS related infections. The evaluation of K. crenata for herb-drug
      interactions has not been reported. This study therefore aims to evaluate the
      risk of K. crenata for herb-drug interaction in vitro. Crude methanol and
      fractions of K. crenata were incubated and preincubated with recombinant human
      CYP2C19 and CYP3A4. Comparative studies were conducted in both human liver
      microsomes and recombinant human CYP to ascertain the inhibition profile of the
      crude extract and the various fractions. The cocktail approach of recombinant
      human CYPs was conducted to confirm the inhibition potential of the fractions in
      the presence of other CYPs. The results showed significant time-dependent
      inhibition of tested samples on CYP3A4 with crude methanol (39KC), fractions 45A,
      45B and 45D given IC50 fold decrease of 3.29, 2.26, 1.91 and 1.49, respective.
      Time dependent kinetic assessment of 39KC and 45D showed KI and kinact values for
      39KC as 1.77 ug/mL and 0.091 min(-1) while that of 45D were 6.45 ug/mL and 0.024
      min(-1), respectively. Determination of kinact based on IC50 calculations yielded
      0.015 and 0.04 min(-1) for 39KC and 45D, respectively. Cocktail approach
      exhibited fold decreases in IC50 for all test fractions on CYP3A4 within the
      ranges of 2.10 - 4.10. At least one phytoconstituent in the crude methanol
      extract of Kalanchoe crenata is a reversible and time-dependent inhibitor of
      CYP3A4.

PMID- 25600203
TI  - Metabolism and Disposition of Pacritinib (SB1518), an Orally Active Janus Kinase
      2 Inhibitor in Preclinical Species and Humans.
AB  - The ADME of Pacritinib (SB1518), an orally active JAK 2 inhibitor, was
      investigated in vitro and in vivo in preclinical species and humans. Pacritinib
      showed ~5 fold higher affinity to human plasma proteins relative to mouse in
      vitro. It was metabolized by human CYP3A4 in vitro, and did not significantly
      induce CYP3A and 1A2 in human hepatocytes. In vitro metabolism studies with mouse
      and human liver microsomes showed the presence of four major metabolites of
      Pacritinib -M1 (oxidation), M2 (dealkylation), M3 (oxidation), M4 (reduction).
      The in vitro and in vivo metabolic patterns observed in mice and humans were in
      good agreement. Qualitatively and quantitatively, none of the metabolites formed
      in vivo was >10% of Pacritinib in mouse, dog and humans. Pacritinib showed
      systemic clearance of 8.0, 1.6, 1.6 l/h/kg, volume of distribution of 14.2, 7.9,
      8.5 l/kg, t1/2 of 5.6, 6.0, 4.6 h, and oral bioavailability of 39, 10, and 24% in
      mouse, rat and dog, respectively. In radiolabeled mass balance and QWBA studies
      in mice, ~91% of the dose was recovered in feces, suggesting biliary clearance,
      and maximum radioactivity was seen in the gastrointestinal tract followed by the
      kidney, heart and low activity in the brain. The relatively high exposures of
      Pacritinib in humans might be attributed to its very high plasma protein binding,
      low metabolic and/or biliary clearance.

PMID- 25600205
TI  - Two hundred laryngeal cancers: patterns of growth and spread as seen in serial
      section. 1977.

PMID- 25600204
TI  - Human HepaRG Cells can be Cultured in Hanging-drop Plates for Cytochrome P450
      Induction and Function Assays.
AB  - Recent guidance/guidelines for industry recommend that cytochrome P450 induction
      can be assessed using human hepatocyte enzyme activity and/or mRNA levels to
      evaluate potential drug- drug interactions. To evaluate time-dependent cytochrome
      P450 induction precisely, induction of CYP1A2, CYP2B6, and CYP3A4 mRNA was
      confirmed (>2-fold) by the treatment with omeprazole, phenobarbital, and
      rifampicin, respectively, for 24 or 48 h on day 3 from the start of culture.
      After 24 h, the fold induction of CYP1A2 with 3.6 and 1.8x10(4) HepaRG cells per
      well was lower than that for 7.2x10(4) cells. CYP1A2 induction levels at 24 h
      were higher than those after 48 h. In contrast, higher CYP2B6 inductions were
      confirmed after 48 h exposure than after 24 h, independent of the number of cells
      per well. To help reduce the use of human cryopreserved hepatocytes, typical P450
      dependent enzyme activities were investigated in human HepaRG cells cultured in
      commercial hanging-drop plates. Newly designed 96-well hanging-drop plates were
      capable of maintaining human CYP3A-dependent midazolam hydroxylation activities
      for up to 4 days using only 10% of the recommended initial 7.2x10(4) cells per
      well. Favorable HepaRG function using hanging-drop plates was confirmed by
      detecting 1'- hydroxymidazolam O-glucuronide on day 3, suggesting an improvement
      over traditional control plates in which this metabolite can be detected for 24
      well plates. These results suggest that the catalytic function and/or induction
      of CYP1A2, CYP2B6, and CYP3A4 can be readily assessed with reduced numbers of
      starting HepaRG cells cultured in three-dimensional cultures in drops prepared
      with hanging-drop plates.

PMID- 25600206
TI  - Transformation products of antibiotic and cytostatic drugs in the aquatic cycle
      that result from effluent treatment and abiotic/biotic reactions in the
      environment: an increasing challenge calling for higher emphasis on measures at
      the beginning of the pipe.
AB  - Pharmaceuticals may undergo transformation into new products during almost all
      possible processes along their life-cycle. This could either take place in the
      natural water environment and/or during water treatment processes. Numerous
      studies that address the issue of such transformation products (TPs) have been
      published, describing selected aspects of TPs in the environment and their
      formation within effluent and water treatment processes. In order to exemplify
      the number and quality of information published on TPs, we selected 21 active
      pharmaceutical ingredients from the groups of antibiotics and antineoplastics,
      and assessed the knowledge about their TPs that has been published until the end
      of May 2012. The goal of this work was to demonstrate, that the quality of data
      on pharmaceutical TPs greatly differs in terms of the availability of chemical
      structures for each TP, rather than to provide an exhaustive database of
      available TPs. The aim was to point out the challenge going along with so many
      TPs formed under different treatment and environmental conditions. An extensive
      review in the form of a table showing the existing data on 158 TPs for 15
      compounds, out of 21 investigated, was presented. Numerous TPs are the result of
      different treatments and environmental processes. However, also numerous
      different TPs may be formed within only one type of treatment, applied under
      sometimes even very similar treatment conditions and treatments times. In
      general, the growing number of elucidated TPs is rationalized by ineffective
      removal treatments. Our results demonstrate a severe risk of drowning in much
      unrelated and non-assessable data, both from a scientific and from a technical
      treatment-related point of view. Therefore, limiting the input of pharmaceuticals
      into effluents as well as improving their (bio) degradability and elimination
      behavior, instead of only relying on advanced effluent treatments, is urgently
      needed. Solutions that focus on this "beginning of the pipe" approach should
      minimize the adverse effects of parent compounds by reducing and formation of TPs
      and their entrance into the natural environment. 

PMID- 25600207
TI  - Next generation sequencing of the hepatitis C virus NS5B gene reveals potential
      novel S282 drug resistance mutations.
AB  - Identifying HCV drug resistance mutations (DRMs) is increasingly important as new
      direct acting antiviral therapies (DAA) become available. Tagged pooled
      pyrosequencing (TPP) was originally developed as cost-effective approach for
      detecting low abundance HIV DRMs. Using 127 HCV-positive samples from a Canadian
      injection drug user cohort, we demonstrated the suitability and efficiency of TPP
      for evaluating DRMs in HCV NS5B gene. At a mutation identification threshold of
      1%, no nucleoside inhibitor DRMs were detected among these DAA naive subjects.
      Clinical NS5B resistance to non-nucleoside inhibitors and interferon/ribavirin
      was predicted to be low within this cohort. S282T mutation, the primary mutation
      selected by sofosbuvir in vitro, was not identified while S282G/C/R variants were
      detected in 9 subjects. Further characterization on these new S282 variants using
      in silico molecular modeling implied their potential association with resistance.
      Combining TPP with in silico analysis detects NS5B polymorphisms that may explain
      differences in treatment outcomes.

PMID- 25600209
TI  - The 10 key steps for radiographic analysis of adolescent idiopathic scoliosis.

PMID- 25600208
TI  - Success rates in pediatric WPW ablation are improved with 3-dimensional mapping
      systems compared with fluoroscopy alone: a multicenter study.
AB  - INTRODUCTION: Three-dimensional mapping (3-D) systems are frequently used for
      ablation of supraventricular tachycardia. Prior studies have demonstrated
      radiation dosage reduction with 3-D, but there are no data on whether 3-D
      improves the efficacy of ablation of Wolff-Parkinson-White syndrome (WPW). We
      sought to determine if 3-D improves the success rate for ablation of WPW in
      children. METHODS: Multicenter retrospective study including patients <=21 years
      of age with WPW undergoing ablation from 2008 to 2012. Success rates using the 2
      techniques (3-D vs. fluoroscopy alone [FLUORO]) were compared. RESULTS: Six
      hundred and fifty-one cases were included (58% male, mean age 13 +/- 4 years, 366
      [56%] 3-D). Baseline characteristics including gender, weight, accessory pathway
      (AP) location, number of APs, and repeat ablation attempts were similar between
      the 2 groups (3-D and FLUORO) The 3-D group was slightly younger (12.7 +/- 4.0
      vs. 13.3 +/- 4.0 years; P = 0.04) and less likely to undergo ablation utilizing
      cryoenergy (38 [10%] vs. 56 [20%]; P < 0.01). The 3-D group had a higher acute
      success rate of ablation (355 [97%] vs. 260 [91%]; P < 0.01). No differences were
      seen in recurrence (16 [5%] vs. 26 [9%]; P = 0.09) or complication rates (1
      [0.3%] vs. 1 [0.4%]; P = 0.86) between the groups. On multivariable analysis, 3-D
      was shown to significantly improve success at ablation with an odds ratio of 3.1
      (95% CI 1.44-6.72; P < 0.01). CONCLUSIONS: Use of 3-D significantly improved
      success rates for ablation of WPW in children. The increase in acute success
      associated with 3-D suggests it is an important adjunct for catheter ablation of
      WPW in children.

PMID- 25600210
TI  - Nursing students' knowledge and attitude on pressure ulcer prevention evidence
      based guidelines: a multicenter cross-sectional study.
AB  - BACKGROUND: Pressure ulcers still remain a significant problem in many healthcare
      settings. Poor knowledge and negative attitudes toward pressure ulcer prevention
      could undesirably affect preventive care strategies. OBJECTIVE: To assess both
      knowledge and attitudes among nursing students on Pressure Ulcer Prevention
      Evidence-Based Guidelines. DESIGN: A multicenter cross-sectional survey was
      carried out from December 2012 to August 2013. SETTINGS: The study was carried
      out in seven Italian nursing schools. PARTICIPANTS: We involved a convenience
      sample of nursing students (n=742) METHODS: Data were collected using two
      validated questionnaires to assess students' knowledge and attitudes on pressure
      ulcer prevention. RESULTS: The overall Knowledge and Attitude scores were 51.1%
      (13.3/26) and 76.7% (39.9/52), respectively. We found a weak correlation between
      total Knowledge scores and total Attitude scores (rho=0.13, p<0.001). We also
      observed that nursing students' year of education, training experience and number
      of department frequented during their clinical placement were significantly
      related to both the Knowledge and the Attitude total scores (p<0.05).
      CONCLUSIONS: Nursing students' knowledge on pressure ulcer prevention was
      relatively low. However, we observed an association between a high level of
      education/training experience and higher knowledge scores. Most of the
      participants showed high attitude scores. These results suggest that positive
      attitudes toward pressure ulcer prevention may contribute to the compliance with
      the guidelines in clinical practice.

PMID- 25600211
TI  - Therapeutic window for cyclooxygenase-2 related anti-inflammatory therapy after
      status epilepticus.
AB  - As a prominent inflammatory effector of cyclooxygenase-2 (COX-2), prostaglandin
      E2 (PGE2) mediates brain inflammation and injury in many chronic central nervous
      system (CNS) conditions including seizures and epilepsy, largely through its
      receptor subtype EP2. However, EP2 receptor activation might also be
      neuroprotective in models of excitotoxicity and ischemia. These seemingly
      incongruent observations expose the delicacy of immune and inflammatory signaling
      in the brain; thus the therapeutic window for quelling neuroinflammation might
      vary with injury type and target molecule. Here, we identify a therapeutic window
      for EP2 antagonism to reduce delayed mortality and functional morbidity after
      status epilepticus (SE) in mice. Importantly, treatment must be delayed relative
      to SE onset to be effective, a finding that could be explained by the time-course
      of COX-2 induction after SE and compound pharmacokinetics. A large number of
      inflammatory mediators were upregulated in hippocampus after SE with COX-2 and IL
      1beta temporally leading many others. Thus, EP2 antagonism represents a novel
      anti-inflammatory strategy to treat SE with a tightly-regulated therapeutic
      window. 

PMID- 25600212
TI  - PTEN deletion from adult-generated dentate granule cells disrupts granule cell
      mossy fiber axon structure.
AB  - Dysregulation of the mTOR-signaling pathway is implicated in the development of
      temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate
      granule cells leads to mTOR hyperactivation and promotes the rapid onset of
      spontaneous seizures. The mechanism by which these abnormal cells initiate
      epileptogenesis, however, is unclear. PTEN-knockout granule cells develop
      abnormally, exhibiting morphological features indicative of increased excitatory
      input. If these cells are directly responsible for seizure genesis, it follows
      that they should also possess increased output. To test this prediction, dentate
      granule cell axon morphology was quantified in control and PTEN-knockout mice.
      Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the
      axon length, suggesting reduced innervation of CA3. Increased width of the mossy
      fiber axon pathway in stratum lucidum, however, which likely reflects an unusual
      increase in mossy fiber axon collateralization in this region, offsets the
      reduction in boutons per axon length. These morphological changes predict a net
      increase in granule cell innervation of CA3. Increased diameter of axons from
      PTEN-knockout cells would further enhance granule cell communication with CA3.
      Altogether, these findings suggest that amplified information flow through the
      hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse
      model of temporal lobe epilepsy. 

PMID- 25600214
TI  - Coaxial Zn2GeO4@carbon nanowires directly grown on Cu foils as high-performance
      anodes for lithium ion batteries.
AB  - A single-step chemical vapor deposition method is utilized to prepare a novel
      electrode structure composed of coaxial Zn2GeO4@carbon nanowires directly grown
      on a Cu foil current-collector (ZGO@C/Cu), and the obtained ZGO@C/Cu hybrid
      electrode is employed as additive-free anode in lithium ion battery studies. The
      ZGO@C/Cu electrode exhibits a high reversible capacity of 1162 mA h g(-1) between
      0.01 and 3.0 V at a current density of 0.2 A g(-1). It also shows a remarkable
      cycling stability and an excellent high-rate capability. At a current density of
      2.0 A g(-1), a stable capacity of 790 mA h g(-1) is obtained without any
      noticeable decay over 100 cycles. Even at a high current density of 10 A g(-1), a
      reversible capacity of 465 mA h g(-1) is still obtained. The synthesis approach
      developed here could be utilized for the fabrication of other high-performance
      heterogeneous electrode structures for lithium ion battery applications. 

PMID- 25600213
TI  - Mitochondrial respiration deficits driven by reactive oxygen species in
      experimental temporal lobe epilepsy.
AB  - Metabolic alterations have been implicated in the etiology of temporal lobe
      epilepsy (TLE), but whether or not they have a functional impact on cellular
      energy producing pathways (glycolysis and/or oxidative phosphorylation) is
      unknown. The goal of this study was to determine if alterations in cellular
      bioenergetics occur using real-time analysis of mitochondrial oxygen consumption
      and glycolytic rates in an animal model of TLE. We hypothesized that increased
      steady-state levels of reactive oxygen species (ROS) initiated by epileptogenic
      injury result in impaired mitochondrial respiration. We established methodology
      for assessment of bioenergetic parameters in isolated synaptosomes from the
      hippocampus of Sprague-Dawley rats at various times in the kainate (KA) model of
      TLE. Deficits in indices of mitochondrial respiration were observed at time
      points corresponding with the acute and chronic phases of epileptogenesis. We
      asked if mitochondrial bioenergetic dysfunction occurred as a result of increased
      mitochondrial ROS and if it could be attenuated in the KA model by
      pharmacologically scavenging ROS. Increased steady-state ROS in mice with
      forebrain-specific conditional deletion of manganese superoxide dismutase
      (Sod2(fl/fl)NEX(Cre/Cre)) in mice resulted in profound deficits in mitochondrial
      oxygen consumption. Pharmacological scavenging of ROS with a catalytic
      antioxidant restored mitochondrial respiration deficits in the KA model of TLE.
      Together, these results demonstrate that mitochondrial respiration deficits occur
      in experimental TLE and ROS mechanistically contribute to these deficits.
      Furthermore, this study provides novel methodology for assessing cellular
      metabolism during the entire time course of disease development.

PMID- 25600215
TI  - Reliability and validity of the Chinese version of the Nutritional Form For the
      Elderly.
AB  - OBJECTIVE: The present study aimed to translate the English version of the
      Nutritional Form For the Elderly into Simplified Chinese, as well as to test the
      reliability (homogeneity and stability) and validity (content and construct
      validity) of the Chinese version of the Nutritional Form For the Elderly (NUFFE
      CHI). DESIGN: The study adopted a cross-sectional design. The English version of
      the NUFFE was translated into Simplified Chinese and a questionnaire survey was
      conducted. The data were analysed with statistical methods to estimate the
      homogeneity, stability, content and construct validity. SETTING: Jinzhou City,
      China. SUBJECTS: A total number of 701 community-dwelling older adults answered
      the questionnaire, including background variables and the NUFFE-CHI. A small
      group of the participants (n 50) completed the NUFFE-CHI twice for test-retest
      reliability. RESULTS: Cronbach's alpha was 0.65 and the split-half reliability
      was 0.67. Item-to-total correlation analyses showed that the scale has sufficient
      internal consistency. The test-retest reliability regarding the total scores of
      NUFFE-CHI was reflected in an intra-class correlation coefficient of 0.88. The
      intra-class correlation coefficients between the test and retest of the NUFFE-CHI
      items varied between 0.43 and 0.98. A content validity index of 0.83 explained
      good content validity. Construct validity was demonstrated in an exploratory
      factor analysis with a six-factor solution, explaining 57.65 % of the variance.
      CONCLUSIONS: This first testing of the NUFFE-CHI indicates sufficient evidence
      for reliability, content and construct validity. Further testing studies
      regarding homogeneity, concurrent validity, sensitivity and specificity are
      required before the NUFFE-CHI can be used as a screening instrument in clinical
      settings and in research.

PMID- 25600216
TI  - Purification and photobiochemical profile of photosystem 1 from a high-salt
      tolerant, oleaginous Chlorella (Trebouxiophycaea, Chlorophyta).
AB  - The eukaryotic green alga Chlamydomonas reinhardtii has been studied extensively
      within the biofuel industry as a model organism, as researchers look towards
      algae to provide chemical feedstocks (i.e., lipids) for the production of liquid
      transportation fuels. C. reinhardtii, however, is unsuitable for high-level
      production of such precursors due to its relatively poor lipid accumulation and
      fresh-water demand. In this study we offer insight into the primary light
      harvesting and electron transfer reactions that occur during phototropic growth
      in a high-salt tolerant strain of Chlorella (a novel strain introduced here as
      NE1401), a single-celled eukaryotic algae also in the phylum Chlorophyta. Under
      nutrient starvation many eukaryotic algae increase dramatically the amount of
      lipids stored in lipid bodies within their cell interiors. Microscopy and lipid
      analyses indicate that Chlorella sp. NE1401 may become a superior candidate for
      algal biofuels production. We have purified highly active Photosystem 1 (PS1)
      complexes to study in vitro, so that we may understand further the
      photobiochemisty of this promising biofuel producer and how its characteristics
      compare and contrast with that of the better understood C. reinhardtii. Our
      findings suggest that the PS1 complex from Chlorella sp. NE1401 demonstrates
      similar characteristics to that of C. reinhardtii with respect to light
      harvesting and electron transfer reactions. We also illustrate that the relative
      extent of the light state transition performed by Chlorella sp. NE1401 is smaller
      compared to C. reinhardtii, although they are triggered by the same dynamic light
      stresses. 

PMID- 25600217
TI  - Health-care management of an unexpected case of Ebola virus disease at the
      Alcorcon Foundation University Teaching Hospital.
AB  - INTRODUCTION: The first Ebola virus infected patient outside Africa was diagnosed
      and treated at Alcorcon Foundation University Teaching Hospital (AFUTH). We
      describe the integrated management strategy (medical, occupational health,
      preventive and public health) applied to the case. METHODS: Descriptive study of
      health-care management of an unexpected case of Ebola virus disease (EVD) at
      AFUTH treated on 6 October 2014. We describe the clinical evolution of the
      patient while he was attended at the Emergency Department, the drawing-up process
      of the action protocol, the process of training of hospital staff, the
      administrative management for transferring the patient to the referral centre,
      and the measures implemented for cleaning, disinfection and management of waste.
      Qualitative variables are expressed as percentages. RESULTS: Our centre designed
      and updated, from May to October, five versions of the acting and care protocol
      for patients with EVD. The protocol was in force at the AFUTH when a nursing
      assistant was attended on 6 October 2014. All preventive, diagnostic and
      therapeutic measures outlined in the protocol were applied and 206 professionals
      had received training and information about care procedures with a suspect case.
      CONCLUSION: Health-care management of an unexpected case of EVD was adequate and
      there was no secondary cases in our staff as a result. All resources available
      should be used to fight EVD.

PMID- 25600218
TI  - Diagnosis and antimicrobial treatment of invasive infections due to multidrug
      resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious
      Diseases and Clinical Microbiology.
AB  - The spread of multidrug-resistant Enterobacteriaceae related to the production of
      extended-spectrum beta-lactamases and carbapenemases is a serious public health
      problem worldwide. Microbiological diagnosis and therapy of these infections are
      challenging and controversial. Clinically relevant questions were selected and
      the literature was reviewed for each of them. The information from the selected
      articles was extracted and recommendations were provided and graded according to
      the strength of the recommendations and quality of the evidence. The document was
      opened to comments from the members from the Spanish Society of Infectious
      Diseases and Clinical Microbiology, which were considered for inclusion in the
      final version. Evidence-based recommendations are provided for the use of
      microbiological techniques for the detection of extended-spectrum beta-lactamases
      and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for
      invasive/severe infections caused by these organisms. The absence of randomised
      controlled trials is noteworthy; thus, recommendations are mainly based on
      observational studies (that have important methodological limitations),
      pharmacokinetic and pharmacodynamics models, and data from animal studies.
      Additionally, areas for future research were identified.

PMID- 25600219
TI  - Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide
      and oxygen on general toxicology, neurobehavioral performance, reproduction and
      development in rats. I. Subacute exposures.
AB  - The inhalation toxicity of submarine contaminants is of concern to ensure the
      health of men and women aboard submarines during operational deployments. Due to
      a lack of adequate prior studies, potential general, neurobehavioral,
      reproductive and developmental toxicity was evaluated in male and female rats
      exposed to mixtures of three critical submarine atmospheric components: carbon
      monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen
      (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body
      inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2),
      low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2
      and 15.0% O2), no adverse effects on survival, body weight or histopathology were
      observed. Reproductive, developmental and neurobehavioral performance were
      evaluated after a 28-day exposure in similar atmospheres. No adverse effects on
      estrus phase, mating, gestation or parturition were observed. No developmental or
      functional deficits were observed in either exposed parents or offspring related
      to motor activity, exploratory behavior or higher-level cognitive functions
      (learning and memory). Only minimal effects were discovered in parent-offspring
      emotionality tests. While statistically significant increases in hematological
      parameters were observed in the offspring of exposed parents compared to
      controls, these parameters remained within normal clinical ranges for blood cells
      and components and were not considered adverse. In summary, subacute exposures to
      elevated concentrations of the submarine atmosphere gases did not affect the
      ability of rats to reproduce and did not appear to have any significant adverse
      health effects.

PMID- 25600220
TI  - Cardiomyopathy confers susceptibility to particulate matter-induced oxidative
      stress, vagal dominance, arrhythmia and pulmonary inflammation in heart failure
      prone rats.
AB  - Acute exposure to ambient fine particulate matter (PM2.5) is tied to
      cardiovascular morbidity and mortality, especially among those with prior cardiac
      injury. The mechanisms and pathophysiological events precipitating these outcomes
      remain poorly understood but may involve inflammation, oxidative stress,
      arrhythmia and autonomic nervous system imbalance. Cardiomyopathy results from
      cardiac injury, is the leading cause of heart failure, and can be induced in
      heart failure-prone rats through sub-chronic infusion of isoproterenol (ISO). To
      test whether cardiomyopathy confers susceptibility to inhaled PM2.5 and can
      elucidate potential mechanisms, we investigated the cardiophysiologic,
      ventilatory, inflammatory and oxidative effects of a single nose-only inhalation
      of a metal-rich PM2.5 (580 ug/m(3), 4 h) in ISO-pretreated (35 days * 1.0
      mg/kg/day sc) rats. During the 5 days post-treatment, ISO-treated rats had
      decreased HR and BP and increased pre-ejection period (PEP, an inverse correlate
      of contractility) relative to saline-treated rats. Before inhalation exposure,
      ISO-pretreated rats had increased PR and ventricular repolarization time (QT) and
      heterogeneity (Tp-Te). Relative to clean air, PM2.5 further prolonged PR-interval
      and decreased systolic BP during inhalation exposure; increased tidal volume,
      expiratory time, heart rate variability (HRV) parameters of parasympathetic tone
      and atrioventricular block arrhythmias over the hours post-exposure; increased
      pulmonary neutrophils, macrophages and total antioxidant status one day post
      exposure; and decreased pulmonary glutathione peroxidase 8 weeks after exposure,
      with all effects occurring exclusively in ISO-pretreated rats but not saline
      pretreated rats. Ultimately, our findings indicate that cardiomyopathy confers
      susceptibility to the oxidative, inflammatory, ventilatory, autonomic and
      arrhythmogenic effects of acute PM2.5 inhalation.

PMID- 25600221
TI  - Cardiovascular effects of ozone in healthy subjects with and without deletion of
      glutathione-S-transferase M1.
AB  - CONTEXT: Exposure to ozone has acute respiratory effects, but few human clinical
      studies have evaluated cardiovascular effects. OBJECTIVE: We hypothesized that
      ozone exposure alters pulmonary and systemic vascular function, and cardiac
      function, with more pronounced effects in subjects with impaired antioxidant
      defense from deletion of the glutathione-S-transferase M1 gene (GSTM1 null).
      METHODS: Twenty-four young, healthy never-smoker subjects (12 GSTM1 null) inhaled
      filtered air, 100 ppb ozone and 200 ppb ozone for 3 h, with intermittent
      exercise, in a double-blind, randomized, crossover fashion. Exposures were
      separated by at least 2 weeks. Vital signs, spirometry, arterial and venous blood
      nitrite levels, impedance cardiography, peripheral arterial tonometry, estimation
      of pulmonary capillary blood volume (Vc), and blood microparticles and platelet
      activation were measured at baseline and during 4 h after each exposure. RESULTS:
      Ozone inhalation decreased lung function immediately after exposure (mean +/-
      standard error change in FEV1, air: -0.03 +/- 0.04 L; 200 ppb ozone: -0.30 +/-
      0.07 L; p < 0.001). The immediate post-exposure increase in blood pressure,
      caused by the final 15-min exercise period, was blunted by 200 ppb ozone exposure
      (mean +/- standard error change for air: 16.7 +/- 2.6 mmHg; 100 ppb ozone: 14.5
      +/- 2.4 mmHg; 200 ppb ozone: 8.5 +/- 2.5 mmHg; p = 0.02). We found no consistent
      effects of ozone on any other measure of cardiac or vascular function. All
      results were independent of the GSTM1 genotype. CONCLUSIONS: We did not find
      convincing evidence for early acute adverse cardiovascular consequences of ozone
      exposure in young healthy adults. The ozone-associated blunting of the blood
      pressure response to exercise is of unclear clinical significance.

PMID- 25600222
TI  - Association Between Serum 25-Hydroxy Vitamin D Levels and Blood Pressure Among
      Adolescents in Two Resource-Limited Settings in Peru.
AB  - INTRODUCTION: Serum 25-hydroxyvitamin D (25OHD) deficiency (<50 nmol/l or 20
      ng/ml) has been associated with increased blood pressure (BP) in observational
      studies. A paucity of data on this relationship is available in Latin American or
      child populations. This study investigates the association between 25OHD levels
      and BP in adolescents at risk for vitamin D deficiency in 2 Peruvian settings.
      METHODS: In a population-based study of 1,441 Peruvian adolescents aged 13-15
      years, 1,074 (75%) provided a serum blood sample for 25OHD analysis and BP
      measurements. Relationships between 25OHD and BP metrics were assessed using
      multiple linear regressions, adjusted for anthropometrics and sociodemographic
      factors. RESULTS: 25OHD deficiency was associated with an elevated diastolic BP
      (DBP) (1.09 mm Hg increase, 95% confidence interval: 0.04 to 2.14; P = 0.04)
      compared to nondeficient adolescents. Systolic BP (SBP) trended to increase with
      vitamin D deficiency (1.30 mm Hg increase, 95% confidence interval: -0.13 to
      2.72; P = 0.08). Mean arterial pressure (MAP) was also greater in adolescents
      with 25OHD (1.16 mm Hg increase, 95% confidence interval: 0.10 to 2.22; P =
      0.03). SBP was found to demonstrate a U-shaped relationship with 25OHD, while DBP
      and MAP demonstrated inverse J-shaped relationships with serum 25OHD status. The
      association between 25OHD deficiency and BP was not different across study sites
      (all P >= 0.19). DISCUSSION: Adolescents deficient in 25OHD demonstrated
      increased DBP and MAP and a trend toward increased SBP, when compared to
      nondeficient subjects. 25OHD deficiency early in life was associated with
      elevated BP metrics, which may predispose risk of hypertension later in
      adulthood.

PMID- 25600223
TI  - Lifecourse Adiposity and Blood Pressure Between Birth and 17 Years Old.
AB  - BACKGROUND: Childhood obesity creates a predisposition to develop adult
      hypertension and diabetes. We have identified distinct childhood adiposity
      trajectories associated with increased insulin resistance in early adolescence.
      Our aim was to investigate the relationship between these adiposity trajectories
      with childhood blood pressure (BP) development. METHODS: Adiposity trajectories
      were previously developed by semiparametric modeling using serial anthropometry
      from birth to age 14 from the West Australian Pregnancy Cohort. The association
      between these trajectories and the prevalence of hypertension and prehypertension
      in 17 year olds was assessed by logistic regression. The relationship between
      adiposity trajectories and lifecourse BP was then assessed using linear mixed
      modeling. RESULTS: The study includes 1,023 adolescents with BP measured at age
      17 years. Three of 7 childhood adiposity trajectories (with accelerating
      adiposity) previously related to increased insulin resistance were associated
      with an increased risk of 17-year-old prehypertension or hypertension, compared
      to a referent trajectory of "stable average adiposity" (odds ratio (OR) = 2.9, P
      = 0.007; OR = 3.5, P < 0.001; and OR = 1.8, P = 0.041). One decelerating
      adiposity trajectory from high birth size was associated with significant
      interactions with age terms (P values = 0.025-0.084 and 0.011-0.027), indicating
      an altered slope and therefore, relative decline in lifecourse BP compared to the
      reference adiposity trajectory. CONCLUSIONS: Adiposity trajectories (which
      comprise 27% of the population) were associated with an increased risk of
      hypertension/prehypertension in adolescence. Higher BP was detectable as early as
      3 years old. Consequently, targeting fat loss (catch-down growth) in the
      preschool years may prevent the development of hypertension and related metabolic
      disorders.

PMID- 25600224
TI  - Interaction of DPP10a with Kv4.3 channel complex results in a sustained current
      component of human transient outward current Ito.
AB  - The sustained component of the K(+) outward current in human atrial myocytes is
      believed to be due to the slowly inactivating ultra-rapid potassium current I Kur
      and not to the fast inactivating transient outward current Ito. Here we provide
      evidence for contribution of Ito to this late current due to the effects of
      dipeptidyl peptidase-like protein (DPP) 10 (DPP10a) interacting with Kv4.3
      channels. We studied the late current component of Ito in human atrial myocytes
      and CHO cells co-expressing Kv4.3 or Kv4.3/KChIP2 (control) and DPP proteins
      using voltage-clamp technique and a pharmacological approach. A voltage dependent
      and slowly inactivating late current (43% of peak amplitude) could be observed in
      atrial myocytes. We found a similar current in CHO cells expressing Kv4.3/KChIP2
      + DPP10a, but not in cells co-expressing Kv4.3 + DPP or Kv4.3/KChIP2 + DPP6-S.
      Assuming that DPP10a influences atrial Ito, we detected DPP10 expression of three
      alternatively spliced mRNAs, DPP10 protein and colocalization of Kv4.3 and DPP10
      proteins in human atrial myocytes. DPP10a did not affect properties of expressed
      Kv1.5 excluding a contribution to the sustained IKur in atrial cells. To test for
      the contribution of Kv4-based Ito on sustained K(+) outward currents in human
      atrial myocytes, we used 4-AP to block IKur, in combination with Heteropoda toxin
      2 to block Kv4 channels. We could clearly separate an Ito fraction of about 19%
      contributing to the late current in atrial myocytes. Thus, the interaction of
      DPP10a, expressed in human atrium, with Kv4.3 channels generates a sustained
      current component of Ito, which may affect late repolarization phase of atrial
      action potentials.

PMID- 25600225
TI  - Mst1 inhibition rescues beta1-adrenergic cardiomyopathy by reducing myocyte
      necrosis and non-myocyte apoptosis rather than myocyte apoptosis.
AB  - It is generally held that inhibition of mammalian sterile 20-like kinase 1 (Mst1)
      protects the heart through reducing myocyte apoptosis. We determined whether
      inhibition with a dominant-negative Mst1 (DN-Mst1) would protect against the
      cardiomyopathy induced by chronic beta1-adrenergic receptor (beta1-AR)
      stimulation by preventing myocyte apoptosis. DN-Mst1 mice were mated with beta1
      AR transgenic (Tg) mice and followed for 20 months. beta1-AR Tg mice developed
      cardiomyopathy as they aged, as reflected by premature mortality and depressed
      cardiac function, which were rescued in beta1-AR * DN-Mst1 bigenic mice.
      Surprisingly, myocyte apoptosis did not significantly decrease with Mst1
      inhibition. Instead, Mst1 inhibition predominantly reduced non-myocyte apoptosis,
      e.g., fibroblasts, macrophages, neutrophils and endothelial cells. Fibrosis in
      the hearts with cardiomyopathy increased fivefold and this increase was nearly
      abolished in the bigenic mice with Mst1 inhibition. Regression analysis showed no
      correlation between myocyte apoptosis and cardiac function or myocyte number,
      whereas the latter two correlated significantly, p < 0.05, with fibrosis, which
      generally results from necrosis. To examine the role of myocyte necrosis, chronic
      beta-AR stimulation with isoproterenol was induced for 24 h and myocyte necrosis
      was assessed by 1% Evans blue dye. Compared to WT, DN-Mst1 mice showed
      significant inhibition, p < 0.05, of myocyte necrosis. We confirmed this result
      in Mst1-knockout mice, which also showed significant protection, p < 0.05,
      against myocyte necrosis compared to WT. These data indicate that Mst1 inhibition
      rescued cardiac fibrosis and myocardial dysfunction in beta1-AR cardiomyopathy.
      However, this did not occur through Mst1 inhibition of myocyte apoptosis but
      rather by inhibition of cardiomyocyte necrosis and non-myocyte apoptosis,
      features of Mst1 not considered previously.

PMID- 25600227
TI  - Gliptin and GLP-1 analog treatment improves survival and vascular
      inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia.
AB  - Dipeptidyl peptidase (DPP)-4 inhibitors are used to treat hyperglycemia by
      increasing the incretin glucagon-like peptide-1 (GLP-1). Previous studies showed
      anti-inflammatory and antiatherosclerotic effects of DPP-4 inhibitors. Here, we
      compared the effects of linagliptin versus sitagliptin and liraglutide on
      survival and vascular function in animal models of endotoxic shock by
      prophylactic therapy and treatment after lipopolysaccharide (LPS) injection.
      Gliptins were administered either orally or subcutaneously: linagliptin (5
      mg/kg/day), sitagliptin (50 mg/kg/day) or liraglutide (200 ug/kg/day). Endotoxic
      shock was induced by LPS injection (mice 17.5-20 mg/kg i.p., rats 10 mg/kg/day).
      Linagliptin and liraglutide treatment or DPP-4 knockout improved the survival of
      endotoxemic mice, while sitagliptin was ineffective. Linagliptin, liraglutide and
      sitagliptin ameliorated LPS-induced hypotension and vascular dysfunction in
      endotoxemic rats, suppressed inflammatory parameters such as whole blood nitrosyl
      iron hemoglobin (leukocyte-inducible nitric oxide synthase activity) or aortic
      mRNA expression of markers of inflammation as well as whole blood and aortic
      reactive oxygen species formation. Hemostasis (tail bleeding time, activated
      partial thromboplastin time) was impaired in endotoxemic rats and recovered under
      cotreatment with linagliptin and liraglutide. Finally, the beneficial effects of
      linagliptin on vascular function and inflammatory parameters in endotoxemic mice
      were impaired in AMP-activated kinase (alpha1) knockout mice. The improved
      survival of endotoxemic animals and other data shown here may warrant further
      clinical evaluation of these drugs in patients with septic shock beyond the
      potential improvement of inflammatory complications in diabetic individuals with
      special emphasis on the role of AMP-activated kinase (alpha1) in the DPP-4/GLP-1
      cascade. 

PMID- 25600226
TI  - Molecular and cellular function of the proprotein convertase subtilisin/kexin
      type 9 (PCSK9).
AB  - The proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a
      promising treatment target to lower serum cholesterol, a major risk factor of
      cardiovascular diseases. Gain-of-function mutations of PCSK9 are associated with
      hypercholesterolemia and increased risk of cardiovascular events. Conversely,
      loss-of-function mutations cause low-plasma LDL-C levels and a reduction of
      cardiovascular risk without known unwanted effects on individual health.
      Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C
      by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). A
      number of clinical studies have demonstrated that inhibition of PCSK9 alone and
      in addition to statins potently reduces serum LDL-C concentrations. This review
      summarizes the current data on the regulation of PCSK9, its molecular function in
      lipid homeostasis and the emerging evidence on the extra-hepatic effects of
      PCSK9. 

PMID- 25600228
TI  - Spatial and temporal variability of fluoride concentrations in groundwater
      resources of Larestan and Gerash regions in Iran from 2003 to 2010.
AB  - There is discrepancy about intervals of fluoride monitoring in groundwater
      resources by Iranian authorities. Spatial and temporal variability of fluoride in
      groundwater resources of Larestan and Gerash regions in Iran were analyzed from
      2003 to 2010 using a geospatial information system and the Mann-Kendall trend
      test. The mean concentrations of fluoride for the 8-year period in the eight
      cities and 31 villages were 1.6 and 2.0 mg/l, respectively; the maximum values
      were 2.4 and 3.8 mg/l, respectively. Spatial, temporal, and spatiotemporal
      variability of fluoride in overall groundwater resources were relatively constant
      over the years. However, results of the Mann-Kendall trend test revealed a
      monotonic trend in the time series of one city and 11 villages for the 8-year
      period. Specifically, one city and three villages showed positive significant
      Kendall's Tau values, suggesting an upward trend in fluoride concentrations over
      the 8-year period. In contrast, seven villages displayed negative significant
      Kendall's Tau values, arguing for a downward trend in fluoride concentrations
      over the years. From 2003 to 2010, approximately 52 % of the Larestan and Gerash
      areas have had fluoride concentrations above the maximum permissible Iranian
      drinking water standard fluoride level (1.4 mg/l), and about 116,000 people were
      exposed to such excess amounts. Therefore, our study supports for a close
      monitoring of fluoride concentrations from health authorities in monthly
      intervals, especially in villages and cities that showed positive trend in
      fluoride concentrations. Moreover, we recommend simultaneous implementation of
      cost-effective protective measures or interventions until a standard fluoride
      level is achieved. 

PMID- 25600229
TI  - Bornean orangutan geophagy: analysis of ingested and control soils.
AB  - Geophagy among orangutans is the most poorly documented in contrast to the
      knowledge of soil-eating practices of other great ape species. Observations of
      soil consumption by orangutans in the Sungai Wain Forest Preserve (Wanariset) of
      Borneo are presented, along with physico-mineral-chemical analyses of the
      ingested soil in an effort to understand what might stimulate the activity. The
      consumed soils are: light colored, not excessively weathered by normal standards,
      higher in the clay size fraction relative to controls, and are comprised of a mix
      of clay minerals without any specificity of 1:1, 2:1 and/or 2:1:1 (Si:Al)
      species. The geophagic soils contain chlorides below detection limits,
      effectively eliminating salt as a stimulus. Soil chemical and geochemical
      analyses confirm that orangutans prefer soils with pH levels near or above 4.0,
      while controls are consistently lower (pH = 3.5-4.0), a considerable difference
      in acidity for at least four out of six soils consumed. Geochemical analysis
      shows Al, Fe and K are high in the consumed vs control samples; higher Al follows
      from higher clay percentages in the consumed earth. Iron and K may play
      physiological roles, but Fe is mostly in the ferrous form (Fe(+2)) and may not be
      readily taken up by the animals. The preferential choice of consumed samples,
      with pH above 4.0 and higher clay contents, may promote a more beneficial
      intestinal environment. 

PMID- 25600230
TI  - Insights into the effects of surface properties of oxides on the catalytic
      activity of Pd for C-C coupling reactions.
AB  - Understanding the interaction between Pd nanocatalysts and metal oxide supports
      for heterogeneous C-C coupling reactions is still ambiguous since many factors
      influence the catalytic behavior of Pd nanocatalysts. Herein, three porous
      nanorods of CeO2 with controllable surface properties were employed as supports
      for Pd nanocatalysts with similar dispersion, which avoided the impact of other
      factors including surface area, morphology and accessible active sites. It
      provides an ideal approach to probe synergetic catalytic behavior of metal
      nanoparticles on supports. The results obtained by studying three C-C coupling
      reactions (Ullman, Suzuki and Heck) indicate a strong correlation between the
      surface properties of supports and the catalytic activity of Pd nanocatalysts:
      supports with a strong basicity and a high concentration of oxygen vacancies
      result in a rich electron density of Pd and accelerate the first step of
      oxidative addition reaction for C-C coupling. The infrared spectroscopic study on
      nu[CO] of CO-treated catalysts and XPS analysis of the Pd(3d) core level provide
      strong evidence supporting the interaction of Pd/supports for C-C coupling
      reactions. 

PMID- 25600231
TI  - Stakeholder engagement analysis - a bioethics dilemma in patient-targeted
      intervention: patients with temporomandibular joint disorders.
AB  - Modern health care in the field of Medicine, Dentistry and Nursing is grounded in
      fundamental philosophy and epistemology of translational science. Recently in the
      U.S major national initiatives have been implemented in the hope of closing the
      gaps that sometimes exist between the two fundamental components of translational
      science, the translational research and translational effectiveness. Subsequent
      to these initiatives, many improvements have been made; however, important
      bioethical issues and limitations do still exist that need to be addressed. One
      such issue is the stakeholder engagement and its assessment and validation.
      Federal, state and local organizations such as PCORI and AHRQ concur that the key
      to a better understanding of the relationship between translational research and
      translational effectiveness is the assessment of the extent to which stakeholders
      are actively engaged in the translational process of healthcare. The stakeholder
      engagement analysis identifies who the stakeholders are, maps their contribution
      and involvement, evaluates their priorities and opinions, and accesses their
      current knowledge base. This analysis however requires conceptualization and
      validation from the bioethics standpoint. Here, we examine the bioethical dilemma
      of stakeholder engagement analysis in the context of the person-environment fit
      (PE-fit) theoretical model. This model is an approach to quantifying stakeholder
      engagement analysis for the design of patient-targeted interventions. In our
      previous studies of Alzheimer patients, we have developed, validated and used a
      simple instrument based on the PE-fit model that can be adapted and utilized in a
      much less studied pathology as a clinical model that has a wide range of symptoms
      and manifestations, the temporomandibular joint disorders (TMD). The
      temporomandibular joint (TMJ) is the jaw joint endowed with sensory and motor
      innervations that project from within the central nervous system and its
      dysfunction can be manifested systemically in forms of movement disorders, and
      related pathological symptomatologies.Currently, there is limited reliable
      evidence available to fully understand the complexity of the various domains of
      translational effectiveness, particularly in the context of stakeholder
      engagement and its assessment, validation as well as the bioethical implications
      as they pertain to evidence-based, effectivness-focused and patient-centered
      care. 

PMID- 25600232
TI  - Position specific differences in the anthropometric characteristics of elite
      European Super League rugby players.
AB  - Rugby league is a collision sport which traditionally adopts a large emphasis on
      lean muscle mass. Currently there is limited research on the anthropometry of
      European Super League players. The aim of this study was to assess body
      composition using Dual Energy X-ray Absorptiometry (DXA) scans to identify the
      typical profile of elite rugby league players. One hundred and twelve players
      from five different clubs competing in the European Super League were recruited
      for the study. DXA scans were performed and the total mass, lean mass, fat mass
      and percentage body fat were reported for each positional group. For the Fullback
      and Wingers, Centres, Half Backs, Hookers, Props and Back Row Forwards the mean
      (SD) body fat percentage was 13 (2.1), 13 (2.4), 12 (3.4), 15 (3.9), 16 (4.3) and
      15 (2.1)%, respectively, and total mass was 86 (8.2), 91 (6.6), 81 (8), 84 (9.5)
      102 (8.5) and 93 (5.5) kg, respectively. Despite small to very large inter
      positional differences in all anthropometric variables (effect sizes = -0.08 to
      2.56), particularly between the Prop and the other playing positions, there was
      large intra-position variation in body fat, lean mass and total mass making a
      standardised position specific profile difficult to establish. When used with
      other key performance indicators, these data provide the first multi-team
      anthropometric profile of elite Super League players that can be used to guide
      individualised training and nutrition practices for current and aspiring
      athletes. 

PMID- 25600233
TI  - Evaluation of ED patient and visitor understanding of living wills and do-not
      resuscitate orders.

PMID- 25600234
TI  - Tranexamic acid in brain injury: devil in the detail.

PMID- 25600235
TI  - A case of the vacuum phenomenon as a mechanism of gas production in the abdominal
      wall.
AB  - A 40-year-old man experienced a collision with a car while driving a motorcycle
      in which the car was in the opposite lane and made a right turn. The patient was
      thrown approximately 10 m from the point of collision and, as he exhibited a
      consciousness disturbance, was transferred to our department. He had a score of
      13 on the Glasgow Coma Scale with sinus tachycardia on arrival. He showed
      guarding of the abdomen. A pan scan disclosed traumatic subarachnoid hemorrhage,
      intraventricular hemorrhage, fractures of the atlas, thoracic spine, sternum and
      left femur, and gas in the abdomen located just in front of the stomach. As the
      gas in the abdomen was initially judged to be free air, the patient underwent
      emergency laparotomy. However, no signs of perforation or injury were detected
      throughout the entire digestive tract. The accumulation of minute gas (vacuum
      phenomenon) occurs as traumatic impact. As representative mimics of free air were
      not observed during surgery in the present case, we believe that the traumatic
      impact to the patient's abdomen as a result of the collision caused the
      accumulation of gas in the abdominal wall due to vacuum phenomenon. Physicians
      should be aware of this clinical entity to accurately recognize the mechanism of
      gas formation in patients showing negative laparotomy findings for gas in the
      abdomen. This unique case adds additional information regarding the documented
      etiologies of mimics of pneumoperitoneum.

PMID- 25600236
TI  - Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale
      building blocks of adherens junctions.
AB  - E-cadherin is the major adhesion receptor in epithelial adherens junctions, which
      connect cells to form tissues and are essential for morphogenesis and
      homeostasis. The mechanism by which E-cadherin monomers cluster and become
      organized in adherens junctions remains poorly understood. Here, using
      superresolution microscopy techniques in combination with structure-informed
      functional mutations, we found that loosely organized clusters of approximately
      five E-cadherin molecules that form independently of cis or trans interactions,
      and that are delimited by the cortical F-actin meshwork, are the precursors of
      trans-ligated adhesive clusters that make up the adherens junction. The density
      of E-cadherin clusters was wide ranged, and notably, we could detect densities
      consistent with the crystal lattice structure at the core of adhesive clusters,
      which were dependent on extracellular domain interactions. Thus, our results
      elucidate the nanoscale architecture of adherens junctions, as well as the
      molecular mechanisms driving its assembly. 

PMID- 25600238
TI  - Salicylic acids as readily available starting materials for the synthesis of meta
      substituted biaryls.
AB  - Salicylic acids are shown to be readily available and versatile starting
      materials that easily undergo a tandem arylation-protodecarboxylation process
      under Pd-catalysis. The corresponding meta-arylphenols can subsequently be easily
      transformed into a variety of meta-functionalized biaryls, highlighting the
      versatility of this approach to access this structural motif. 

PMID- 25600237
TI  - Interkinetic nuclear migration is centrosome independent and ensures apical cell
      division to maintain tissue integrity.
AB  - Pseudostratified epithelia are widespread during animal development and feature
      elongated cells whose nuclei adopt various positions along the apicobasal cell
      axis. Before mitosis, nuclei migrate toward the apical surface, and subsequent
      divisions occur apically. So far, the exact purpose of this nuclear migration
      remained elusive. One hypothesis was that apical migration ensures that nuclei
      and centrosomes meet for mitosis. We here demonstrate that in zebrafish
      neuroepithelia apical nuclear migration occurs independently of centrosome
      position or integrity. It is a highly reproducible phenomenon linked to the cell
      cycle via CDK1 activity. We propose that the robustness of bringing nuclei
      apically for mitosis ensures that cells are capable of reintegrating into the
      epithelium after division. Nonapical divisions lead to cell delamination and
      formation of cell clusters that subsequently interfere with neuronal layering.
      Therefore, positioning divisions apically in pseudostratified neuroepithelia
      could serve to safeguard epithelial integrity and enable proper proliferation and
      maturation. 

PMID- 25600239
TI  - Amount of organic matter required to induce sulfate reduction in sulfuric
      material after re-flooding is affected by soil nitrate concentration.
AB  - Acid sulfate soils (ASS) with sulfuric material can be remediated through
      microbial sulfate reduction stimulated by adding organic matter (OM) and
      increasing the soil pH to >4.5, but the effectiveness of this treatment is
      influenced by soil properties. Two experiments were conducted using ASS with
      sulfuric material. In the first experiment with four ASS, OM (finely ground
      mature wheat straw) was added at 2-6% (w/w) and the pH adjusted to 5.5. After 36
      weeks under flooded conditions, the concentration of reduced inorganic sulfur
      (RIS) and pore water pH were greater in all treatments with added OM than in the
      control without OM addition. The RIS concentration increased with OM addition
      rate. The increase in RIS concentration between 4% and 6% OM was significant but
      smaller than that between 2% and 4%, suggesting other factors limited sulfate
      reduction. In the second experiment, the effect of nitrate addition on sulfate
      reduction at different OM addition rates was investigated in one ASS. Organic
      matter was added at 2 and 4% and nitrate at 0, 100, and 200 mg nitrate-N kg(-1).
      After 2 weeks under flooded conditions, soil pH and the concentration of FeS
      measured as acid volatile sulfur (AVS) were lower with nitrate added at both OM
      addition rates. At a given nitrate addition rate, pH and AVS concentration were
      higher at 4% OM than at 2%. It can be concluded that sulfate reduction in ASS at
      pH 5.5 can be limited by low OM availability and high nitrate concentrations.
      Further, the inhibitory effect of nitrate can be overcome by high OM addition
      rates.

PMID- 25600241
TI  - A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug
      delivery.
AB  - Lysosomes of brain capillary endothelial cells are implicated in nicotine
      acetylcholine receptor (nAChR)-mediated transcytosis and act as an enzymatic
      barrier for the transport of peptide ligands to the brain. A D-peptide ligand of
      nAChRs (termed (D)CDX), which binds to nAChRs with an IC50 value of 84.5 nM, was
      developed by retro-inverso isomerization. (D)CDX displayed exceptional stability
      in lysosomal homogenate and serum, and demonstrated significantly higher
      transcytosis efficiency in an in vitro blood-brain barrier monolayer compared
      with the parent L-peptide. When modified on liposomal surface, (D)CDX facilitated
      significant brain-targeted delivery of liposomes. As a result, brain-targeted
      delivery of (D)CDX modified liposomes enhanced therapeutic efficiency of
      encapsulated doxorubicin for glioblastoma. This study illustrates the importance
      of ligand stability in nAChRs-mediated transcytosis, and paves the way for
      developing stable brain-targeted entities.

PMID- 25600242
TI  - Choledochal cyst mimicking Mirizzi's syndrome A case report.
AB  - Choledochal cysts are cystic dilatations of the intra or extra-hepatic biliary
      tract with an incidence of 1 case per 150.000 live births. Cysts usually are
      diagnosed in childhood, but diagnosis can be delayed until adulthood in the 20
      50% of cases. Clinical manifestations comprise abdominal pain with biliary or
      pancreatic features. Mirizzi's syndrome is a late and rare complication, that
      occurs in 1% of patients with cholelithiasis due to extrinsic compression of the
      common bile duct by stones impacted either in the gallbladder or in the cystic
      duct. Clinical symptoms include extrahepatic obstructive jaundice, ascending
      cholangitis, or, in the later course, cholecystocholedocal fistula. For both
      pathologies the Endoscopic Retrograde Cholangio Pancreatography and the Magnetic
      Resonance Cholangio Pancreatography should lead to the diagnosis with a
      sensibility and a specificity up to 100%. We report the case of a 66 year old
      patient admitted to the Emergency Department of our hospital for jaundice and
      abdominal pain, whom both the endoscopic and radiologic examination showed a
      Mirizzi's syndrome but surgery revealed a type I choledocal cyst.

PMID- 25600243
TI  - High Ki-67 Expression and Low Progesterone Receptor Expression Could
      Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen
      Receptor-Positive and HER2-Negative Breast Cancer.
AB  - We examined the prognostic significance of progesterone receptor (PgR) expression
      in immunohistochemical-based luminal subtypes defined by Ki-67 expression, taking
      menopausal status into consideration. The study included 327 surgically removed
      estrogen receptor-positive and human epidermal growth factor receptor 2-negative
      breast cancers. High Ki-67 expression (> 15%) and low PgR expression (L 20%) were
      significant independent factors resulting in worse distant relapse-free survival.
      This association was observed in postmenopausalwomen but not in premenopausal
      women. BACKGROUND: Accurate classification of luminal A and luminal B
      characteristics of estrogen receptor (ER)-positive and human epidermal growth
      factor receptor 2 (HER2)-negative breast cancer is considered clinically
      important for determining effective adjuvant treatment. Although Ki-67 expression
      has been identified as an essential constituent for this classification, the role
      of progesterone receptor (PgR) expression has yet to be fully elucidated. Because
      PgR expression is influenced by the estrogen milieu, we examined the prognostic
      significance of PgR expression in immunohistochemical (IHC)-based luminal
      subtypes defined by Ki-67 expression, taking menopausal status into
      consideration. MATERIALS AND METHODS: We examined 327 surgically removed ER(+)
      and HER2(-) breast cancer specimens. ER, PgR, and Ki67 expression was determined
      IHC for semiquantitative measurement. We used 1%, 20%, and 15% as the cutoff
      value for ER, PgR, and Ki-67, respectively. RESULTS: Breast cancer with low PgR
      (<= 20%) expression was significantly associated with postmenopausal status, a
      large tumor size, and low ER expression. The low PgR expression subset had
      significantly worse distant relapse-free survival (DRFS) than the high PgR
      expression subset (P = .0067). This association was observed consistently in
      postmenopausal women but not in the premenopausal women. Multivariate analysis
      demonstrated that high Ki-67 expression (hazard ratio [HR], 3.80; 95% confidence
      interval [CI], 1.57-10.58; P = .003) and low PgR expression (HR, 2.54; 95% CI,
      1.08-6.40; P = .038) were significant independent factors affecting DRFS.
      CONCLUSION: Low PgR expression was independently associated with a poorer
      prognosis for ER(+) and HER2(-) breast cancer. Determination of PgR expression
      combined with that of Ki-67 could thus improve the accuracy of IHC-based
      classification of luminal A and luminal B breast cancer, especially for
      postmenopausal women.

PMID- 25600244
TI  - Activation of mTOR/S6K But Not MAPK Pathways Might Be Associated With High Ki-67,
      ER(+), and HER2(-) Breast Cancer.
AB  - We determined the activation of the phosphoinositide 3-kinase (PI3K) and mitogen
      activated protein kinase (MAPK) signaling pathways in 108 cases of estrogen
      receptor-positive and human epidermal growth factor receptor 2-negative breast
      cancer with high and low Ki-67 expression. The expression levels of Ki-67, p53,
      phosphorylated MAPK (pMAPK), and protein S6 (pS6; downstream molecule of
      PI3K/Akt/mammalian target of rapamycin/S6 kinase pathway) were determined
      immunohistochemically. pS6 positivity, but not pMAPK positivity, was
      significantly associated with the high Ki-67 expression subset. BACKGROUND:
      Evaluation of luminal A and luminal B characteristics of estrogen receptor (ER)
      positive and human epidermal growth factor receptor 2 (HER2)-negative breast
      cancer is considered important. Although the phosphoinositide 3 kinase (PI3K) and
      mitogen-activated protein kinase (MAPK) signaling pathways are thought to be
      involved in the luminal B subtype, the details of their contribution to breast
      cancer remain unclear. MATERIALS AND METHODS: We determined the activation of
      these pathways (phosphorylated MAPK [pMAPK] and protein S6 [pS6; a downstream
      molecule of PI3K/Akt/mammalian target of rapamycin (mTOR)/S6 kinase (S6K)]) in
      108 ER(+), HER2(-) breast cancer cases with high and low Ki-67 expression. The
      ER, progesterone receptor (PgR), Ki-67, p53 expression levels were also
      determined immunohistochemically. The cutoff value for Ki-67 was set at 15%.
      RESULTS: A significantly greater percentage of cancer cases with high Ki-67
      expression showed pS6 positivity than did those with low Ki-67 expression (53.2%
      vs. 19.7%; P = .0003). No significant differences were found between the cases
      with high and low expression levels were detected for p53 (23.4% vs. 11.5%; P =
      .12) or pMAPK (36.2% vs. 34.4%; P = .85) positivity. Multivariate analysis showed
      that pS6 positivity (odds ratio 5.16, 95% confidence interval 1.95-13.63; P =
      .0009), nuclear grade 2 and 3, and low PgR expression (<= 20%) were independently
      associated with the high Ki-67 subset. CONCLUSION: From our findings, we have
      concluded that the pS6 expression level is associated with the characteristics of
      breast cancer with high Ki-67 expression. Because these associations were
      observed, irrespective of menopausal status, the biologic difference seems to be
      less affected by estrogen signaling than by activation of S6 protein, especially
      in terms of proliferation. Our findings have also indicated that targeting the
      mTOR/S6K pathway might be a useful strategy for the treatment of ER(+)/HER2(-)
      breast cancer with high Ki-67 expression.

PMID- 25600245
TI  - Intravenous self-administration of mephedrone, methylone and MDMA in female rats.
AB  - Male rats will intravenously self-administer (IVSA) the substituted cathinone
      stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4
      methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4
      methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There
      are no data available on the self-administration of these drugs in female rats,
      thus a study was undertaken to contrast them directly. Groups of female 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 PR (0.125, 1.0 mg/kg/inf) dose-substitution
      procedures. The results show that female rats acquired the self-administration of
      all three compounds with intakes in mephedrone-trained rats that were
      significantly higher than that of methylone-trained or MDMA-trained rats. In dose
      substitution under either FR or PR contingencies, however, the potencies of all
      three drugs were similar within the original training groups. The mephedrone
      trained animals exhibited higher intakes of all drugs during dose-substitution,
      indicating lasting consequences of the training drug. Abuse liability of these
      three compounds is therefore predicted to be similar in established stimulant
      users but may differ in liability if they are primary drugs of initiation.

PMID- 25600246
TI  - Short-term efficacy of recombinant human GH therapy in cured acromegaly patients
      with GH deficiency: a single-center experience.
AB  - The effectiveness and short-term safety of recombinant human GH (r-hGH) in
      acromegaly patients with GH deficiency (GHD) after treatment are not well
      established. The study includes ten subjects with acromegaly who had GHD treated
      with r-hGH for 6 months. Control groups consisted of ten age-, gender-, and BMI
      matched healthy subjects and ten active acromegaly patients who were treatment
      naive. Body composition, quality of life (QoL), muscle strength, lipid profile,
      and cardiovascular risk factors were assessed in all subjects at baseline, and
      the same parameters were reassessed after 6 months of therapy with r-hGH in
      acromegaly with GHD. Repeat magnetic resonance imaging of the sella was performed
      in treated subjects. Optical colonoscopy was done and biopsies were taken from
      multiple sites for proliferation indices (Ki67). The median duration of GHD was
      17.8 months and dose of r-hGH administered was 5.7+/-1.5 MUg/kg per day. There
      was improvement in bone mineral content (P=0.01), bone mineral density (P=0.04),
      muscle strength (P<0.001), total cholesterol (P=0.003), high-density cholesterol
      (P<0.001), and QoL - score (P=0.005), and reduction in low-density cholesterol
      (P=0.003) and triglyceride (P=0.004) after treatment. There was no change in lean
      body mass, total body fat, hsCRP, lipoprotein (a), and fibrinogen levels. There
      was a modest increase in plasminogen activator inhibitor 1 (P=0.002), but it was
      lower compared with healthy controls and treatment naive acromegalics (P=0.007).
      Six month-r-hGH therapy improves body composition, atherogenic lipid profile,
      QoL, and muscle strength in GHD patients who had acromegaly. Long-term
      prospective studies are needed to evaluate the effect of r-hGH therapy in these
      patients. 

PMID- 25600247
TI  - Impact of functional appliances on muscle activity: a surface electromyography
      study in children.
AB  - BACKGROUND: Electromyography (EMG) is the most objective tool for assessing
      changes in the electrical activity of the masticatory muscles. The purpose of the
      study was to evaluate the tone of the masseter and anterior temporalis muscles in
      growing children before and after 6 months of treatment with functional removable
      orthodontic appliances. MATERIAL/METHODS: The sample conisted of 51 patients with
      a mean age 10.7 years with Class II malocclusion. EMG recordings were performed
      by using a DAB-Bluetooth instrument (Zebris Medical GmbH, Germany). Recordings
      were performed in mandibular rest position, during maximum voluntary contraction
      (MVC), and during maximum effort. RESULTS: The results of the study indicated
      that the electrical activity of the muscles in each of the clinical situations
      was the same in the group of girls and boys. The factor that determined the
      activity of the muscles was their type. In mandibular rest position and in MVC,
      the activity of the temporalis muscles was significantly higher that that of the
      masseter muscels. The maximum effort test indicated a higher fatigue in masseter
      than in temporalis muscles. CONCLUSIONS: Surface electromyography is a useful
      tool for monitoring muscle activity. A 6-month period of functional therapy
      resulted in changes in the activity of the masticatory muscles.

PMID- 25600248
TI  - Effect of canagliflozin on serum uric acid in patients with type 2 diabetes
      mellitus.
AB  - Hyperuricaemia is associated with an increased risk of gout, kidney stones and
      cardiovascular disease. The present post hoc analysis of pooled data from four
      placebo-controlled phase III studies assessed the effect of canagliflozin, a
      sodium-glucose co-transporter 2 inhibitor, on serum uric acid levels in patients
      with type 2 diabetes mellitus (T2DM) and in a subset of patients with
      hyperuricaemia [defined as baseline serum uric acid >=475 umol/l (~8 mg/dl)]. At
      week 26, canagliflozin 100 and 300 mg were associated with a ~13% reduction in
      serum uric acid compared with placebo. In the subset of patients with
      hyperuricaemia, placebo-subtracted percent reductions in serum uric acid were
      similar to those in the overall cohort. More patients in the hyperuricaemic group
      achieved a serum uric acid level of <360 umol/l (~6 mg/dl) with both
      canagliflozin 100 mg (23.5%) and 300 mg (32.4%) compared with placebo (3.1%).
      Incidences of gout and kidney stones were low and similar across groups. In
      conclusion, canagliflozin treatment decreased serum uric acid in patients with
      T2DM, including those with baseline hyperuricaemia. 

PMID- 25600249
TI  - A pilot study on the feasibility and acceptability of a text message-based
      aftercare treatment programme among alcohol outpatients.
AB  - AIMS: To test the feasibility, acceptability and initial effectiveness of a text
      message-based aftercare treatment programme among alcohol outpatients. METHODS:
      Clients treated for alcohol use disorders from three Swiss outpatient alcohol
      treatment centres were invited by their counsellors to participate in a study
      testing an interactive aftercare programme employing the use of text messages and
      personal phone calls. Fifty study participants were randomly assigned to either
      the 6-month aftercare programme (n = 25) or treatment as usual (n = 25). The
      intervention consisted of (a) monitoring of self-selected drinking goals at
      regular intervals, (b) motivational text messages to stick to self-selected
      drinking goals and (c) proactive telephone calls from counsellors when
      participants neglected to stick to their drinking goals or expressed a need for
      support. Follow-up interviews were conducted 6 months after randomization.
      RESULTS: Throughout the programme, participants received a total of 421 text
      message prompts. Out of these, participants provided valid replies to 371 (88.1%)
      within 48 h. Out of the 25 participants in the intervention group, 11 (44.0%)
      sent at least one call-for-help reply. Based on complete case data, at risk
      alcohol use at follow-up was 41.7% in the control group and 28.6% in the
      intervention group (OR = 0.56, 95% CI = 0.16-1.95, P = 0.36). CONCLUSIONS: The
      interactive low-intensive aftercare programme was well accepted by the
      participants. Testing its efficacy within an adequately powered randomized
      controlled trial might be reasonable.

PMID- 25600250
TI  - Identification of novel osteogenic compounds by an ex-vivo sp7:luciferase
      zebrafish scale assay.
AB  - Tight interactions among different cell types contributing to bone formation are
      of key importance in the maintenance of bone homeostasis. Based on the high
      similarity in responses to (anti)osteogenic signals between zebrafish scales and
      mammalian bone, we developed and validated a model to screen large numbers of
      compounds using ex-vivo cultured scales of a sp7:luciferase transgenic zebrafish.
      This model combines the high predictive value of explant cultures with quick,
      sensitive, and quantifiable readout converging the effects via various pathways
      including WNT-signaling, to SP7/osterix promoter activity. Sp7 is pivotal in
      osteoblast differentiation and activity and its promoter activity provides an
      excellent surrogate for sp7 expression. Bmp-2a was shown to dose-dependently
      increase sp7-driven luciferase activity ex vivo. Next, we identified novel
      effects on bone for 51.7% of the compounds from a small library of WNT-signaling
      modulators, including a strong osteogenic effect for niclosamide. From all
      previously characterized compounds, the effect on bone was correctly predicted
      for 70% of compounds, resulting in a 7% false positive- and 21% false negative
      rate. The proposed sp7:luciferase zebrafish scale model is unique, powerful and
      efficient new tool to assess compounds with osteogenic effects, prior to further
      testing in rodents. 

PMID- 25600251
TI  - [Onychomycosis due to yeasts: Agents and a sensitivity study in the Valparaiso
      region, Chile].

PMID- 25600252
TI  - Theileria equi isolates vary in susceptibility to imidocarb dipropionate but
      demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.
AB  - BACKGROUND: The apicomplexan hemoparasite Theileria equi is a causative agent of
      equine piroplasmosis, eradicated from the United States in 1988. However, recent
      outbreaks have sparked renewed interest in treatment options for infected horses.
      Imidocarb dipropionate is the current drug of choice, however variation in
      clinical response to therapy has been observed. METHODS: We quantified the in
      vitro susceptibility of two T. equi isolates and a lab generated variant to both
      imidocarb dipropionate and a bumped kinase inhibitor compound 1294. We also
      evaluated the capacity of in vitro imidocarb dipropionate exposure to decrease
      susceptibility to that drug. The efficacy of imidocarb dipropionate for clearing
      infection in four T. equi infected ponies was also assessed. RESULTS: We observed
      an almost four-fold difference in imidocarb dipropionate susceptibility between
      two distinct isolates of T. equi. Four ponies infected with the less susceptible
      USDA Florida strain failed to clear the parasite despite two rounds of treatment.
      Importantly, a further 15-fold decrease in susceptibility was produced in this
      strain by continuous in vitro imidocarb dipropionate exposure. Despite a
      demonstrated difference in imidocarb dipropionate susceptibility, there was no
      difference in the susceptibility of two T. equi isolates to bumped kinase
      inhibitor 1294. CONCLUSIONS: The observed variation in imidocarb dipropionate
      susceptibility, further reduction in susceptibility caused by drug exposure in
      vitro, and failure to clear T. equi infection in vivo, raises concern for the
      emergence of drug resistance in clinical cases undergoing treatment. Bumped
      kinase inhibitors may be effective as alternative drugs for the treatment of
      resistant T. equi parasites.

PMID- 25600253
TI  - Patients' perceived value of pharmacy quality measures: a mixed-methods study.
AB  - OBJECTIVE: To describe patients' perceived value and use of quality measures in
      evaluating and choosing community pharmacies. DESIGN: Focus group methodology was
      combined with a survey tool. During the focus groups, participants assessed the
      value of the Pharmacy Quality Alliance's quality measures in evaluating and
      choosing a pharmacy. Also, participants completed questionnaires rating their
      perceived value of quality measures in evaluating a pharmacy (1 being low value
      and 5 being high) or choosing a pharmacy (yes/no). Thematic analysis and
      descriptive statistics were used to analyse the focus groups and surveys,
      respectively. SETTING: Semistructured focus groups were conducted in a private
      meeting space of an urban and a rural area of a Mid-western State in the USA.
      PARTICIPANTS: Thirty-four adults who filled prescription medications in community
      pharmacies for a chronic illness were recruited in community pharmacies, senior
      centres and public libraries. RESULTS: While comments indicated that all measures
      were important, medication safety measures (eg, drug-drug interactions) were
      valued more highly than others. Rating of quality measure utility in evaluating a
      pharmacy ranged from a mean of 4.88 ('drug-drug interactions') to a mean of 4.0
      ('absence of controller therapy for patients with asthma'). Patients were
      hesitant to use quality information in choosing a pharmacy (depending on the
      participant's location) but might consider if moving to a new area or having had
      a negative pharmacy experience. Use of select quality measures to choose a
      pharmacy ranged from 97.1% of participants using 'drug-drug interactions'
      (medication safety measure) to 55.9% using 'absence of controller therapy for
      patients with asthma'. CONCLUSIONS: The study participants valued quality
      measures in evaluating and selecting a community pharmacy, with medication safety
      measures valued highest. The participants reported that the quality measures
      would not typically cause a switch in pharmacy but might influence their
      selection in certain situations.

PMID- 25600254
TI  - Understanding the role of physician attire on patient perceptions: a systematic
      review of the literature--targeting attire to improve likelihood of rapport
      (TAILOR) investigators.
AB  - OBJECTIVES: Despite a growing body of literature, uncertainty regarding the
      influence of physician dress on patients' perceptions exists. Therefore, we
      performed a systematic review to examine the influence of physician attire on
      patient perceptions including trust, satisfaction and confidence. SETTING,
      PARTICIPANTS, INTERVENTIONS AND OUTCOMES: We searched MEDLINE, Embase, Biosis
      Previews and Conference Papers Index. Studies that: (1) involved participants
      >=18 years of age; (2) evaluated physician attire; and (3) reported patient
      perceptions related to attire were included. Two authors determined study
      eligibility. Studies were categorised by country of origin, clinical discipline
      (eg, internal medicine, surgery), context (inpatient vs outpatient) and
      occurrence of a clinical encounter when soliciting opinions regarding attire.
      Studies were assessed using the Downs and Black Scale risk of bias scale. Owing
      to clinical and methodological heterogeneity, meta-analyses were not attempted.
      RESULTS: Of 1040 citations, 30 studies involving 11 533 patients met eligibility
      criteria. Included studies featured patients from 14 countries. General medicine,
      procedural (eg, general surgery and obstetrics), clinic, emergency departments
      and hospital settings were represented. Preferences or positive influence of
      physician attire on patient perceptions were reported in 21 of the 30 studies
      (70%). Formal attire and white coats with other attire not specified was
      preferred in 18 of 30 studies (60%). Preference for formal attire and white coats
      was more prevalent among older patients and studies conducted in Europe and Asia.
      Four of seven studies involving procedural specialties reported either no
      preference for attire or a preference for scrubs; four of five studies in
      intensive care and emergency settings also found no attire preference. Only 3 of
      12 studies that surveyed patients after a clinical encounter concluded that
      attire influenced patient perceptions. CONCLUSIONS: Although patients often
      prefer formal physician attire, perceptions of attire are influenced by age,
      locale, setting and context of care. Policy-based interventions that target such
      factors appear necessary.

PMID- 25600255
TI  - Clinical effects of blood donor characteristics in transfusion recipients:
      protocol of a framework to study the blood donor-recipient continuum.
AB  - INTRODUCTION: When used appropriately, transfusion of red blood cells (RBCs) is a
      necessary life-saving therapy. However, RBC transfusions have been associated
      with negative outcomes such as infection and organ damage. Seeking explanations
      for the beneficial and deleterious effects of RBC transfusions is necessary to
      ensure the safe and optimal use of this precious resource. This study will create
      a framework to analyse the influence of blood donor characteristics on recipient
      outcomes. METHODS AND ANALYSIS: We will conduct a multisite, longitudinal cohort
      study using blood donor data routinely collected by Canadian Blood Services, and
      recipient data from health administrative databases. Our project will include a
      thorough validation of primary data, the linkage of various databases into one
      large longitudinal database, an in-depth epidemiological analysis and a careful
      interpretation and dissemination of the results to assist the decision-making
      process of clinicians, researchers and policymakers in transfusion medicine. Our
      primary donor characteristic will be age of blood donors and our secondary donor
      characteristics will be donor-recipient blood group compatibility and blood donor
      sex. Our primary recipient outcome will be a statistically appropriate survival
      analysis post-RBC transfusion up to a maximum of 8 years. Our secondary recipient
      outcomes will include 1-year, 2-year and 5-year mortality; hospital and intensive
      care unit length of stay; rehospitalisation; new cancer and cancer recurrence
      rate; infection rate; new occurrence of myocardial infarctions and need for
      haemodialysis. ETHICS AND DISSEMINATION: Our results will help determine whether
      we need to tailor transfusion based on donor characteristics, and perhaps this
      will improve patient outcome. Our results will be customised to target the
      different stakeholders involved with blood transfusions and will include
      presentations, peer-reviewed publications and the use of the dissemination
      network of blood supply organisations. We obtained approval from the Research
      Ethics boards and privacy offices of all involved institutions.

PMID- 25600256
TI  - Big data and clinicians: a review on the state of the science.
AB  - BACKGROUND: In the past few decades, medically related data collection saw a huge
      increase, referred to as big data. These huge datasets bring challenges in
      storage, processing, and analysis. In clinical medicine, big data is expected to
      play an important role in identifying causality of patient symptoms, in
      predicting hazards of disease incidence or reoccurrence, and in improving primary
      care quality. OBJECTIVE: The objective of this review was to provide an overview
      of the features of clinical big data, describe a few commonly employed
      computational algorithms, statistical methods, and software toolkits for data
      manipulation and analysis, and discuss the challenges and limitations in this
      realm. METHODS: We conducted a literature review to identify studies on big data
      in medicine, especially clinical medicine. We used different combinations of
      keywords to search PubMed, Science Direct, Web of Knowledge, and Google Scholar
      for literature of interest from the past 10 years. RESULTS: This paper reviewed
      studies that analyzed clinical big data and discussed issues related to storage
      and analysis of this type of data. CONCLUSIONS: Big data is becoming a common
      feature of biological and clinical studies. Researchers who use clinical big data
      face multiple challenges, and the data itself has limitations. It is imperative
      that methodologies for data analysis keep pace with our ability to collect and
      store data.

PMID- 25600257
TI  - Association between diabetes and amyotrophic lateral sclerosis in Sweden.
AB  - BACKGROUND AND PURPOSE: Energy metabolism is altered in patients with amyotrophic
      lateral sclerosis (ALS) but the role of diabetes is largely unknown. METHODS: A
      population-based case-control study was conducted of 5108 ALS cases and 25,540
      individually matched population controls during 1991-2010. Information on ALS and
      pre-existing diabetes was retrieved from the Swedish Patient Register to explore
      the association of ALS with diabetes overall and with insulin-dependent or non
      insulin-dependent diabetes specifically. Variation of the association by diabetes
      duration and age was also studied. RESULTS: In total, 224 ALS cases (4.39%) and
      1437 controls (5.63%) had diabetes before the index date, leading to an overall
      inverse association between diabetes and ALS risk [odds ratio (OR) 0.79, 95%
      confidence interval (CI) 0.68-0.91]. The association was strong for non-insulin
      dependent diabetes (OR 0.66, 95% CI 0.53-0.81) but not for insulin-dependent
      diabetes (OR 0.83, 95% CI 0.60-1.15) and varied as a function of diabetes
      duration, with the strongest association observed around 6 years after first
      ascertainment of diabetes. The association was age-specific; the inverse
      association was noted only amongst individuals aged 70 or older. In contrast, for
      younger individuals (<50 years), pre-existing insulin-dependent diabetes was
      associated with a higher ALS risk (OR 5.38, 95% CI 1.87-15.51). CONCLUSIONS: Our
      study suggests that there is an association between diabetes and ALS, and
      highlights the importance of taking into account age, insulin dependence and
      diabetes duration. Future studies should explore whether the association is
      independent of body mass index.

PMID- 25600258
TI  - Transcutaneous electrical nerve stimulation for chronic post-herpetic neuralgia.
AB  - Postherpetic neuralgia remains a therapeutic challenge for the clinician. Many
      modalities have been utilized with limited success. In this pilot randomized
      study of patients who were refractory to previous medicinal treatment, the
      patients were treated with transcutaneous nerve stimulation with a biofeedback
      capability. After every two treatments with the sham and true device, the
      patients were required to fill out a standard neuropathic pain scale score. The
      patients were allowed to select the other device after three consecutive
      treatments if they felt an inadequate decrease in their pain. The true device was
      chosen over the sham device by all patients. The majority of these patients
      treated by the true device reported a statistically significant decrease in pain
      scores (P < 0.001). Further investigation of this Food and Drug Administration,
      class 2 accepted, electronic device for relief of pain is warranted for patients
      with a history of recalcitrant postherpetic neuralgia. 

PMID- 25600259
TI  - Self-reported activity and functioning in daily life; the perspective of persons
      with haemophilia living in Sweden.
AB  - OBJECTIVES: To investigate the self-estimated function, activity and
      participation in daily life of persons with severe or moderate haemophilia A and
      B (PWH) living in Sweden. The secondary aim was to explore the differences
      between participants with early treatment onset and later. METHODS: The
      Haemophilia Activity List (HAL), Arthritis Impact Measurement Scales (AIMS2) and
      Impact on Participation and Autonomy (IPA-S) were distributed by mail to 225 PWH
      with an invitation to participate in the study. The median and min-max are given
      for the different domains; a higher value indicates more disability. RESULTS:
      Eighty-four PWH (18-80 years) participated. The HAL indicated more problems in
      the legs [40 (0-100)] than in self-care [4 (0-92)] and household tasks [3 (0
      87)]. The AIMS2 scores confirmed this (physical activity 12 (0-64.5) as well as
      somewhat reduced autonomy outdoors [IPA-S 17.5 (0-90)]. More limitations in daily
      life were reported by participants with later treatment onset. CONCLUSION: The
      PWH reported greater disability in the domains related to activities using the
      lower extremities compared to domains related to upper extremity. This study
      pointed out the need of using different questionnaires to capture patients own
      perspective and as useful supplement to other clinical assessment instruments.

PMID- 25600260
TI  - Stopping ovarian cancer screening in BRCA1/2 mutation carriers: effects on risk
      management decisions & outcome of risk-reducing salpingo-oophorectomy specimens.
AB  - OBJECTIVE: Ovarian cancer screening (OCS) for BRCA1/2 mutation carriers was
      stopped in our family cancer clinic in 2009 because of its ineffectiveness. The
      study objective was to investigate the effect of stopping OCS on the timing and
      uptake of risk-reducing salpingo-oophorectomy (RRSO) and on the percentage of
      occult cancers in the specimens. METHODS: 419 BRCA1/2 mutation carriers were
      recruited between January 1999 and June 2013. Uptake, timing and the outcome of
      the RRSO specimens before stopping OCS (period I) were compared to those after
      stopping OCS (period II). RESULTS: The percentage of women undergoing RRSO within
      the recommended age range increased from 81% to 95%. Receiving DNA test results
      in period II independently predicted a shorter time interval to RRSO (hazard
      ratio: 2.48, 95% confidence interval: 1.81-3.39). The incidence of detecting
      occult cancers in RRSO specimens before and after stopping OCS was 1.3% and 1.8%,
      respectively, and was not statistically significantly different. CONCLUSIONS: The
      presentation of risk management options to women may influence their decision.
      The increased patient awareness of the ineffectiveness of OCS could have led to a
      higher percentage of women undergoing RRSO and doing so more often within the
      recommended age range.

PMID- 25600261
TI  - Ultrasonic evaluation of the repair integrity can predict functional outcomes
      after arthroscopic double-row rotator cuff repair.
AB  - PURPOSE: Despite proven accuracy of US for the evaluation of rotator cuff
      integrity, there is no US-based classification for this purpose. This study aimed
      to assess US for the evaluation of rotator cuff repair integrity in accordance
      with a well-established MRI classification. METHODS: The authors retrospectively
      reviewed 257 patients who underwent arthroscopic double-row suture anchor repair
      for rotator cuff tears. Post-operative function was rated using the Constant
      score, the UCLA rating and the SSV, whereas repair integrity was assessed using
      US as described in the MRI classification of Sugaya et al. RESULTS: A total of
      212 patients aged 55.6 +/- 9.8 years had complete functional and radiographic
      assessments at a mean follow-up of 36.8 +/- 11.6 months. Using all three ratings,
      repairs of Type I had highest scores, repairs of Type II had discernibly lower
      scores, whereas repairs of Types III, IV and V had similar intermediate scores.
      CONCLUSION: Comparison of the UCLA scores with those of Sugaya et al. revealed
      similar scores for repairs of Type I and of Type V. The scores are less
      comparable for repairs of Types II, III and IV, because US does not allow
      identification of partial tears if shielded by bony structures and because
      partial tears correspond to minimal impairment. The study reveals that US is an
      adequate imaging modality to classify rotator cuff repair integrity, which could
      reduce economic and practical burdens of CTA, MRI or MRA. The results also
      confirm that post-operative repair integrity and functional outcome depend on pre
      operative tear size and fatty infiltration, which provides clinicians with
      reasoning for early surgical repair and warning of the risks of strenuous
      activity for patients with larger tears. LEVEL OF EVIDENCE: Prognostic study,
      Level IV.

PMID- 25600262
TI  - Comparison of alternate references for femoral rotation in female patients
      undergoing total knee arthroplasty.
AB  - PURPOSE: Accurate rotational alignment of the femoral component is of vital
      importance for successful total knee arthroplasty (TKA). Two anatomical
      references located on the anterior femur were recently introduced. To determine
      which is more reliable reference axis for the femoral component rotation in
      female patients receiving TKA, the trochlear anterior line was compared with the
      femoral anterior tangent line. MATERIALS AND METHODS: Preoperative computed
      tomography in 76 patients receiving TKA for varus deformity was performed, and
      the images were reconstructed into three-dimensional models. The trochlear
      anterior line was defined as the line connecting the most anterior portion of the
      lateral and medial femoral condyles and the femoral anterior tangent line as the
      line parallel to distal anterior femoral surface. The two angles between these
      reference axes and the surgical transepicondylar axis (TEA) in three-dimensional
      images (trochlear anterior line/TEA, femoral anterior tangent line/TEA) were
      measured. The correlation between these two angles was computed. We investigated
      to see whether a significant difference in variance existed. RESULTS: The
      trochlear anterior line was internally rotated by 6.1 degrees  +/- 2.5 degrees 
      with respect to TEA, whereas the femoral anterior tangent line by 9.5 degrees  +/
      3.8 degrees . The trochlear anterior line was externally rotated by 3.4 degrees 
      +/- 3.3 degrees  with respect to the femoral anterior tangent line. There was a
      significant correlation between the trochlear anterior line/TEA and the femoral
      anterior tangent line/TEA. CONCLUSIONS: The variance of the trochlear anterior
      line/TEA was significantly smaller than that of the femoral anterior tangent
      line/TEA demonstrating a more consistent distribution. When conventional
      reference axes such as the posterior condylar axis or the anteroposterior axis
      are unclear or differ, surgeons can rely on these alternative references. When
      trochlear anterior line and femoral anterior tangent line contradicts, the former
      might be more reliable for the rotational alignment of the femoral component in
      female patients. LEVEL OF EVIDENCE: Case series with no comparison group, Level
      IV.

PMID- 25600263
TI  - Anti-TNF levels and anti-drug antibodies, immunosuppressants and clinical
      outcomes in inflammatory bowel disease.
AB  - The anti-tumor necrosis factor-alpha (TNF) antibodies have revolutionized the
      management of ulcerative colitis and Crohn's disease. The development of assays
      to allow for the measurements of serum drug levels and anti-drug antibodies have
      provided a more objective means of therapeutic decision making, particularly
      among patients losing response to treatment. Additionally, more evidence is
      emerging that indicates the relationship between drug levels and response to
      therapy including clinical response, mucosal healing and sustained remission. The
      use of combination therapies of the anti-TNF agents and the thiopurine
      immunosuppressants may also decrease immunogenicity to the anti-TNF agents and
      potentiate response to therapy. With more evidence emerging evidence of the
      importance of therapeutic drug levels and anti-drug antibodies, clinicians may be
      able to better optimize the current arsenal of inflammatory bowel disease
      therapeutics to achieve greater rates of durable remission and improved quality
      of life. 

PMID- 25600264
TI  - Structural elucidation, in vitro antioxidant and photoprotective capacities of a
      purified polyphenolic-enriched fraction from a saltmarsh plant.
AB  - In temperate saltmarshes, halophytic plants have to daily protect their internal
      tissues against sunlight and UV rays. Consequently, they develop adaptive
      responses such as the synthesis of secondary metabolites, including polyphenols.
      The present study focused on the biological activities of fractions enriched in
      polyphenols from Salicornia ramosissima. Three different extracts were obtained
      by purification processes to concentrate polyphenols: a crude hydroalcoholic
      extract, and two purified fractions: an ethyl acetate fraction (EAF) and an
      aqueous fraction. Phenolic and flavonoid contents, antioxidant (DPPH radical
      scavenging activity, reducing activity, beta-carotene linoleic acid system and
      the ORAC method) and sunscreen properties (Sun Protection Factor and UVA
      Protection Factor) were assessed by in vitro tests. The purification process was
      effective in increasing phenolic and flavonoid contents as well as antioxidant
      and sunscreen capacities of the EAF. The EAF appeared to be a broad spectrum UV
      absorber. The chemical structure of 10 EAF polyphenols was elucidated using 2D
      NMR and mass spectrometry spectra. Furthermore, a correlation was observed
      between phenolic composition and biological activity. These findings are
      encouraging for the future use of S. ramosissima as a potential source of
      antioxidant and photoprotectant molecules for industrial applications. 

PMID- 25600265
TI  - Enantiomeric fluoro-substituted benzothiazole Schiff base-valine Cu(II)/Zn(II)
      complexes as chemotherapeutic agents: DNA binding profile, cleavage activity, MTT
      assay and cell imaging studies.
AB  - To evaluate the biological preference of chiral drugs toward DNA target, new
      metal-based chemotherapeutic agents of Cu(II) and Zn(II), l-/d
      fluorobenzothiazole Schiff base-valine complexes 1 &2 (a and b), respectively
      were synthesized and thoroughly characterized. Preliminary in vitro DNA binding
      studies of ligand L and complexes 1 &2 (a and b) were carried out in Tris-HCl
      buffer at pH 7.2 to demonstrate the chiral preference of l-enantiomeric complexes
      over the d-analogues. The extent of DNA binding propensity was ascertained
      quantitatively by Kb, K and Ksv values which revealed greater binding propensity
      by l-enantiomeric Cu(II) complex 1a and its potency to act as a chemotherapeutic
      agent. The cleavage studies with pBR322 plasmid DNA revealed higher nuclease
      activity of 1a as compared to 2avia hydrolytic cleavage mechanism. The complexes
      1 &2 (a and b) were also screened for antimicrobial activity which demonstrated
      significantly good activity for l-enantiomeric complexes. Furthermore,
      cytotoxicity of the complexes 1a and 1b was evaluated by the MTT assay on human
      HeLa cancer cell line which implicated that more than 50% cells were viable at
      15MUM. These results were further validated by cell imaging studies which
      demonstrated the nuclear blebbing. 

PMID- 25600266
TI  - Weekend personal ultraviolet radiation exposure in four cities in Australia:
      influence of temperature, humidity and ambient ultraviolet radiation.
AB  - PURPOSE: To examine the effects of meteorological factors on weekend sun exposure
      behaviours and personal received dose of ultraviolet radiation (UVR) in
      Australian adults. METHODS: Australian adults (n=1002) living in Townsville (19
      degrees S, 146 degrees E), Brisbane (27 degrees S, 153 degrees E), Canberra (35
      degrees S, 149 degrees E) and Hobart (43 degrees S, 147 degrees E) were recruited
      between 2009 and 2010. Data on sun exposure behaviours were collected by daily
      sun exposure dairies; personal UVR exposure was measured with a polysulphone
      dosimeter. Meteorological data were obtained from the Australian Bureau of
      Meteorology; ambient UVR levels were estimated using the Ozone Monitoring
      Instrument data. RESULTS: Higher daily maximum temperatures were associated with
      reduced likelihood of wearing a long-sleeved shirt or wearing long trousers in
      Canberra and Hobart, and higher clothing-adjusted UVR dose in Canberra. Higher
      daily humidity was associated with less time spent outdoors in Canberra. Higher
      ambient UVR level was related to a greater clothing-adjusted personal UVR dose in
      Hobart and a greater likelihood of using sunscreen in Townsville. CONCLUSION: The
      current findings enhance our understanding of the impact of weather conditions on
      the population's sun exposure behaviours. This information will allow us to
      refine current predictive models for UVR-related diseases, and guide future
      health service and health promotion needs.

PMID- 25600267
TI  - G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons.
AB  - The regulated release of anorexigenic alpha-melanocyte stimulating hormone (alpha
      MSH) and orexigenic Agouti-related protein (AgRP) from discrete hypothalamic
      arcuate neurons onto common target sites in the central nervous system has a
      fundamental role in the regulation of energy homeostasis. Both peptides bind with
      high affinity to the melanocortin-4 receptor (MC4R); existing data show that
      alpha-MSH is an agonist that couples the receptor to the Galphas signalling
      pathway, while AgRP binds competitively to block alpha-MSH binding and blocks the
      constitutive activity mediated by the ligand-mimetic amino-terminal domain of the
      receptor. Here we show that, in mice, regulation of firing activity of neurons
      from the paraventricular nucleus of the hypothalamus (PVN) by alpha-MSH and AgRP
      can be mediated independently of Galphas signalling by ligand-induced coupling of
      MC4R to closure of inwardly rectifying potassium channel, Kir7.1. Furthermore,
      AgRP is a biased agonist that hyperpolarizes neurons by binding to MC4R and
      opening Kir7.1, independently of its inhibition of alpha-MSH binding.
      Consequently, Kir7.1 signalling appears to be central to melanocortin-mediated
      regulation of energy homeostasis within the PVN. Coupling of MC4R to Kir7.1 may
      explain unusual aspects of the control of energy homeostasis by melanocortin
      signalling, including the gene dosage effect of MC4R and the sustained effects of
      AgRP on food intake. 

PMID- 25600268
TI  - A temporal shift in the circuits mediating retrieval of fear memory.
AB  - Fear memories allow animals to avoid danger, thereby increasing their chances of
      survival. Fear memories can be retrieved long after learning, but little is known
      about how retrieval circuits change with time. Here we show that the dorsal
      midline thalamus of rats is required for the retrieval of auditory conditioned
      fear at late (24 hours, 7 days, 28 days), but not early (0.5 hours, 6 hours) time
      points after learning. Consistent with this, the paraventricular nucleus of the
      thalamus (PVT), a subregion of the dorsal midline thalamus, showed increased c
      Fos expression only at late time points, indicating that the PVT is gradually
      recruited for fear retrieval. Accordingly, the conditioned tone responses of PVT
      neurons increased with time after training. The prelimbic (PL) prefrontal cortex,
      which is necessary for fear retrieval, sends dense projections to the PVT.
      Retrieval at late time points activated PL neurons projecting to the PVT, and
      optogenetic silencing of these projections impaired retrieval at late, but not
      early, time points. In contrast, silencing of PL inputs to the basolateral
      amygdala impaired retrieval at early, but not late, time points, indicating a
      time-dependent shift in retrieval circuits. Retrieval at late time points also
      activated PVT neurons projecting to the central nucleus of the amygdala, and
      silencing these projections at late, but not early, time points induced a
      persistent attenuation of fear. Thus, the PVT may act as a crucial thalamic node
      recruited into cortico-amygdalar networks for retrieval and maintenance of long
      term fear memories. 

PMID- 25600269
TI  - The paraventricular thalamus controls a central amygdala fear circuit.
AB  - Appropriate responses to an imminent threat brace us for adversities. The ability
      to sense and predict threatening or stressful events is essential for such
      adaptive behaviour. In the mammalian brain, one putative stress sensor is the
      paraventricular nucleus of the thalamus (PVT), an area that is readily activated
      by both physical and psychological stressors. However, the role of the PVT in the
      establishment of adaptive behavioural responses remains unclear. Here we show in
      mice that the PVT regulates fear processing in the lateral division of the
      central amygdala (CeL), a structure that orchestrates fear learning and
      expression. Selective inactivation of CeL-projecting PVT neurons prevented fear
      conditioning, an effect that can be accounted for by an impairment in fear
      conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM(+))
      CeL neurons, which has previously been shown to store fear memory. Consistently,
      we found that PVT neurons preferentially innervate SOM(+) neurons in the CeL, and
      stimulation of PVT afferents facilitated SOM(+) neuron activity and promoted
      intra-CeL inhibition, two processes that are critical for fear learning and
      expression. Notably, PVT modulation of SOM(+) CeL neurons was mediated by
      activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin
      related kinase B (TrkB). As a result, selective deletion of either Bdnf in the
      PVT or Trkb in SOM(+) CeL neurons impaired fear conditioning, while infusion of
      BDNF into the CeL enhanced fear learning and elicited unconditioned fear
      responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel
      circuit essential for both the establishment of fear memory and the expression of
      fear responses, and uncover mechanisms linking stress detection in PVT with the
      emergence of adaptive behaviour. 

PMID- 25600270
TI  - Distinct relationships of parietal and prefrontal cortices to evidence
      accumulation.
AB  - Gradual accumulation of evidence is thought to be fundamental for decision
      making, and its neural correlates have been found in several brain regions. Here
      we develop a generalizable method to measure tuning curves that specify the
      relationship between neural responses and mentally accumulated evidence, and
      apply it to distinguish the encoding of decision variables in posterior parietal
      cortex and prefrontal cortex (frontal orienting fields, FOF). We recorded the
      firing rates of neurons in posterior parietal cortex and FOF from rats performing
      a perceptual decision-making task. Classical analyses uncovered correlates of
      accumulating evidence, similar to previous observations in primates and also
      similar across the two regions. However, tuning curve assays revealed that while
      the posterior parietal cortex encodes a graded value of the accumulating
      evidence, the FOF has a more categorical encoding that indicates, throughout the
      trial, the decision provisionally favoured by the evidence accumulated so far.
      Contrary to current views, this suggests that premotor activity in the frontal
      cortex does not have a role in the accumulation process, but instead has a more
      categorical function, such as transforming accumulated evidence into a discrete
      choice. To probe causally the role of FOF activity, we optogenetically silenced
      it during different time points of the trial. Consistent with a role in
      committing to a categorical choice at the end of the evidence accumulation
      process, but not consistent with a role during the accumulation itself, a
      behavioural effect was observed only when FOF silencing occurred at the end of
      the perceptual stimulus. Our results place important constraints on the circuit
      logic of brain regions involved in decision-making. 

PMID- 25600271
TI  - Growth and host interaction of mouse segmented filamentous bacteria in vitro.
AB  - The gut microbiota plays a crucial role in the maturation of the intestinal
      mucosal immune system of its host. Within the thousand bacterial species present
      in the intestine, the symbiont segmented filamentous bacterium (SFB) is unique in
      its ability to potently stimulate the post-natal maturation of the B- and T-cell
      compartments and induce a striking increase in the small-intestinal Th17
      responses. Unlike other commensals, SFB intimately attaches to absorptive
      epithelial cells in the ileum and cells overlying Peyer's patches. This
      colonization does not result in pathology; rather, it protects the host from
      pathogens. Yet, little is known about the SFB-host interaction that underlies the
      important immunostimulatory properties of SFB, because SFB have resisted in vitro
      culturing for more than 50 years. Here we grow mouse SFB outside their host in an
      SFB-host cell co-culturing system. Single-celled SFB isolated from monocolonized
      mice undergo filamentation, segmentation, and differentiation to release viable
      infectious particles, the intracellular offspring, which can colonize mice to
      induce signature immune responses. In vitro, intracellular offspring can attach
      to mouse and human host cells and recruit actin. In addition, SFB can potently
      stimulate the upregulation of host innate defence genes, inflammatory cytokines,
      and chemokines. In vitro culturing thereby mimics the in vivo niche, provides new
      insights into SFB growth requirements and their immunostimulatory potential, and
      makes possible the investigation of the complex developmental stages of SFB and
      the detailed dissection of the unique SFB-host interaction at the cellular and
      molecular levels. 

PMID- 25600272
TI  - Tooth bleaching with hydrogen peroxide and nano-hydroxyapatite: a 9-month follow
      up randomized clinical trial.
AB  - OBJECTIVES: The aim of this study was to compare the amount of tooth colour
      change, rebound rate and tooth sensitivity in patients submitted to a bleaching
      technique with 6% hydrogen peroxide (HP) with or without 2% nano-hydroxyapatite
      (n-HA). METHODS: Sixty subjects were included in this examiner-blinded,
      randomized clinical trial using a 6% HP gel with or without 2% n-HA. Tooth colour
      and tooth sensitivity were analysed before and after treatment. All data were
      analysed statistically. RESULTS: After bleaching, both treatments demonstrated
      significant improvements in tooth shade (P < 0.05 for both groups). At the 9
      month recall, tooth shade remained significantly lighter than at baseline (P <
      0.05 for both groups). However, a relapse of the tooth shade was observed
      compared with the immediate post-bleaching result (P < 0.05). 6% HP with 2% n-HA
      produced significantly lower sensitivity (P < 0.05) than the bleaching product
      without n-HA. Colour change evaluation resulted in no difference between the two
      groups. CONCLUSION: Both treatments demonstrated significant improvements in
      tooth shade. The bleaching effectiveness of the tested products was comparable.
      The use of 6% HP with 2% n-HA reduced the incidence of sensitivity during the
      bleaching treatment compared to a bleaching agent that did not contain n-HA.

PMID- 25600273
TI  - Growth responses of the mangrove Avicennia marina to salinity: development and
      function of shoot hydraulic systems require saline conditions.
AB  - BACKGROUND AND AIMS: Halophytic eudicots are characterized by enhanced growth
      under saline conditions. This study combines physiological and anatomical
      analyses to identify processes underlying growth responses of the mangrove
      Avicennia marina to salinities ranging from fresh- to seawater conditions.
      METHODS: Following pre-exhaustion of cotyledonary reserves under optimal
      conditions (i.e. 50% seawater), seedlings of A. marina were grown hydroponically
      in dilutions of seawater amended with nutrients. Whole-plant growth
      characteristics were analysed in relation to dry mass accumulation and its
      allocation to different plant parts. Gas exchange characteristics and stable
      carbon isotopic composition of leaves were measured to evaluate water use in
      relation to carbon gain. Stem and leaf hydraulic anatomy were measured in
      relation to plant water use and growth. KEY RESULTS: Avicennia marina seedlings
      failed to grow in 0-5% seawater, whereas maximal growth occurred in 50-75%
      seawater. Relative growth rates were affected by changes in leaf area ratio (LAR)
      and net assimilation rate (NAR) along the salinity gradient, with NAR generally
      being more important. Gas exchange characteristics followed the same trends as
      plant growth, with assimilation rates and stomatal conductance being greatest in
      leaves grown in 50-75% seawater. However, water use efficiency was maintained
      nearly constant across all salinities, consistent with carbon isotopic
      signatures. Anatomical studies revealed variation in rates of development and
      composition of hydraulic tissues that were consistent with salinity-dependent
      patterns in water use and growth, including a structural explanation for low
      stomatal conductance and growth under low salinity. CONCLUSIONS: The results
      identified stem and leaf transport systems as central to understanding the
      integrated growth responses to variation in salinity from fresh- to seawater
      conditions. Avicennia marina was revealed as an obligate halophyte, requiring
      saline conditions for development of the transport systems needed to sustain
      water use and carbon gain.

PMID- 25600274
TI  - [Fetal DNA in maternal plasma and serum].

PMID- 25600275
TI  - [N. Fries and L.J. Salomon in reply to the article by M. Constant: nuchal
      translucency: not so simple! Gynecol Obstet Fertil 2014;42:820-21].

PMID- 25600276
TI  - Postpartum telogen effluvium.

PMID- 25600277
TI  - Familial aggregation of Parkinson's disease in the Faroe Islands.
AB  - The Faroe Islands are a geographic population isolated in the North Atlantic with
      a high prevalence of Parkinson's disease (PD). Although environmental risk
      factors are well described, the familial aggregation of PD on the Islands has yet
      to be explored. Complete ascertainment of all patients with PD was performed,
      including 217 cases and 251 control subjects. All patients were neurologically
      assessed and diagnosed using UK Brain Bank criteria and Hohn and Yahr staging.
      Comprehensive genealogical and detailed cartographic analyses were performed.
      Relative risk and risk ratios were calculated with respect to the general
      population. Patients with PD in the Faroes have a higher age at symptom onset and
      diagnosis than for neighboring countries. Clinically, patients are similar;
      however, they are more likely to have affected relatives than randomly selected
      control subjects, matched by sex and age. Disease is most prevalent within two
      geographic regions. Overall, the relative risk for PD was 2.3 (95% confidence
      interval [CI], 1.2-4.3; P = 0.008) for siblings and 1.4 (95% CI, 1.01-1.99, P =
      0.04) for first cousins. The etiology and excess prevalence of PD on the Faroes
      is complicated. Regional and familial clustering, and subsequent segregation
      analysis, suggests the disease best fits a genetic etiology with limited support
      for an environmental contribution. Pedigree-based analysis of PD on the Faroe
      Islands which has few founders and a relatively homogeneous background may
      elaborate on these possibilities and their joint contribution.

PMID- 25600278
TI  - Reflecting on the interface between alcohol and other drug use, parenting and the
      outcomes for children in the modern state.

PMID- 25600279
TI  - Kinesin-4 Functions in Vesicular Transport on Cortical Microtubules and Regulates
      Cell Wall Mechanics during Cell Elongation in Plants.
AB  - In plants, anisotropic cell expansion depends on cortical microtubules that serve
      as tracks along which macromolecules and vesicles are transported by the motor
      kinesins of unknown identities. We used cotton (Gossypium hirsutum) fibers that
      underwent robust elongation to discover kinesins that are involved in cell
      elongation and found Gh KINESIN-4A expressed abundantly. The motor was detected
      by immunofluorescence on vesicle-like structures that were associated with
      cortical microtubules. In Arabidopsis thaliana, the orthologous motor At KINESIN
      4A/FRA1, previously implicated in cellulose deposition during secondary growth in
      fiber cells, was examined by live-cell imaging in cells expressing the
      fluorescently tagged functional protein. The motor decorated vesicle-like
      particles that exhibit a linear movement along cortical microtubules with an
      average velocity of 0.89 MUm/min, which was significantly different from those
      linked to cellulose biosynthesis. We also discovered that At KINESIN-4A/FRA1 and
      the related At KINESIN-4C play redundant roles in cell wall mechanics, cell
      elongation, and the axial growth of various vegetative and reproductive organs,
      as the loss of At KINESIN-4C greatly enhanced the defects caused by a null
      mutation at the KINESIN-4A/FRA1 locus. The double mutant displayed a lack of cell
      wall softening at normal stages of rapid cell elongation. Furthermore, enhanced
      deposition of arabinose-containing carbohydrate was detected in the kinesin-4
      mutants. Our findings established a connection between the Kinesin-4-based
      transport of cargoes containing non-cellulosic components along cortical
      microtubules and cell wall mechanics and cell elongation in flowering plants. 

PMID- 25600280
TI  - E-cadherin-negative acinar cell carcinoma of the pancreas: report of a case
      showing a solid pseudopapillary growth pattern.
AB  - E-cadherin expression patterns in acinar cell carcinomas (ACCs) of the pancreas
      have not been well documented. Herein, we present a hitherto undescribed case of
      E-cadherin-negative ACC with a solid pseudopapillary growth pattern in a 65-year
      old man. We used an antibody against the extracellular domain of E-cadherin. As a
      further unusual status in ACC, faint beta-catenin expression was observed in the
      cytoplasm of carcinoma cells. Morphological distinction from a solid
      pseudopapillary neoplasm (SPN) of the pancreas might be problematic in such a
      case, because of their similarities concerned with the growth pattern and E
      cadherin negativity. Without nuclear accumulation of beta-catenin, a diagnosis of
      SPN was almost excluded. Immunoreactivity for trypsin and BCL10 made an accurate
      diagnosis of ACC to this case. The tumor recurred 10 months post-surgery as
      rapidly enlarging masses in the liver, presumably indicating the aggressiveness
      of the E-cadherin-negative phenotype among ACCs. 

PMID- 25600281
TI  - Accurate Prediction of the Stage of Histological Chorioamnionitis before Delivery
      by Amniotic Fluid IL-8 Level.
AB  - OBJECTIVE: To estimate the stage of histological chorioamnionitis (h-CAM)
      antenatally using clinical data. MATERIALS AND METHODS: Four hundred and twenty
      eight singleton mothers were recruited. Clinical data including the levels of
      white blood cell count (WBC), C-reactive protein (CRP), amniotic fluid
      interleukin-8 (AF-IL-8) at Cesarean section, and maternal body temperature (MBT)
      were collected. RESULTS: Histological chorioamnionitis was present in 45.3% of
      the cases. Poor neonatal prognosis was highest (59.1%) in cases with h-CAM stage
      III. AF-IL-8 (odds ratio: 8.5, 95% CI: 5.1-14.8, P < 0.0001) and MBT (odds ratio:
      2.3, 95% CI: 1.13-4.1, P = 0.0192) were independent risk factors for h-CAM. The
      cutoff value of AF-IL-8 for predicting each stage of h-CAM (stage I or higher,
      stage II or higher, and stage III) were >=9.9 ng/mL, >=17.3 ng/mL, and >=55.9
      ng/mL, respectively. CONCLUSION: The stage of h-CAM was able to be predicted
      accurately by the level of AF-IL-8 before delivery.

PMID- 25600282
TI  - MicroRNAs in Lung Cancer and Lung Cancer Bone Metastases: Biomarkers for Early
      Diagnosis and Targets for Treatment.
AB  - Lung cancer is the leading cause of malignancy-related mortality worldwide.
      Metastases, which account for 90% of lung cancer deaths, frequently target the
      skeleton, leading to rapid deterioration in quality of life and premature death.
      The molecular mechanism underlying this progression, especially the development
      of bone metastases, is largely unknown. MicroRNAs (miRNAs) are small, endogenous,
      noncoding RNAs that function as negatively posttranscriptional gene regulators.
      Changes in miRNAs, which may exhibit either oncogenic or tumor suppressive
      activity, are common in lung cancer. Over-expressed miRNAs may contribute to
      oncogenesis by down-regulating tumor suppressors, whereas the loss of selected
      miRNAs may negatively regulate oncogenes or factors related to tumorigenesis and
      progression. MiRNAs may activate or repress metastases. Specific miRNA expression
      profiles may correlate with the response in treatment. We summarize recent
      findings and patents in the pathological roles of miRNAs in the progression and
      bone metastases in lung cancer, and discuss the diagnostic and therapeutic
      options in the clinical management of lung cancer. 

PMID- 25600283
TI  - Retrospective chart review of 44 fetuses with cervicofacial tumors in the
      sonographic assessment.
AB  - OBJECTIVES: The aim of this retrospective study was to review and analyze
      ultrasonography examinations and follow-up of fetuses with cervicofacial tumors
      to develop bases for counseling specialist involved in perinatal treatment.
      METHODS: The study consisted of case series with chart review of 44 fetuses with
      cervicofacial tumors diagnosed in utero by ultrasonography. The study was carried
      in Department of Diagnosis and Prevention of Congenital Malformations, Medical
      University of Lodz in years 1998-2013. The analysis of the fetuses with
      cervicofacial tumors included assessment of fetal sonographic features, neonatal
      survival and in utero as well as perinatal treatments. The obtained data were
      analyzed by the standard statistical tests and the Pearson's Chi square test,
      statistical significance at p=0.05. RESULTS: Cervicofacial tumors were detected
      at mean 19+/-7 weeks of gestation. Eighty-two percent of the fetuses were males.
      Lymphatic malformations followed by teratomas were the most common fetal tumors
      in the cervicofacial region. In most cases, fetuses with cervicofacial tumors had
      other abnormalities. Mortality rate in our case series was 43%. In utero
      treatment was introduced in 6 fetuses. In 4 neonates prenatal sonographic
      assessment revealed upper airway patency and EXIT procedure (ex-utero intrapartum
      treatment) was introduced. CONCLUSION: Prenatal sonographic detection of
      cervicofacial tumor, in case of lymphatic malformations possibly as early as in
      the first trimester, in case of craniofacial teratomas, cervical teratomas,
      hemangiomas and thyroid tumors possibly as early as in the second trimester, and
      in case of epignathi possibly in the third trimester, permits planning further
      course of pregnancy as well as EXIT procedure before delivery.

PMID- 25600284
TI  - Atypical Cogan's syndrome: a case report and summary of current treatment
      options.
AB  - Cogan's syndrome is a rare chronic vasculitis, characterized in its typical form
      by progressive sensorineural bilateral hearing loss, vestibular symptoms and non
      syphilitic interstitial keratitis. Only a few cases have been reported in
      children, most of whom have been diagnosed with the typical form. Early diagnosis
      and treatment are crucial to ensure a favorable prognosis. Systemic treatment
      usually begins with high dosage corticosteroids. In case the initial treatment
      fails, other immunosuppressive drugs are used (cyclophosphamide, methotrexate,
      cyclosporine A and azathioprine). Additional treatment possibilities, such as
      plasmapheresis, TNF-alpha blockers (etanercept and infliximab), rituximab,
      tocilizumab and mycophenolate mofetil have been described over the past few
      years. 

PMID- 25600286
TI  - Balloon Angioplasty for the Treatment of Left Innominate Vein Obstruction Related
      Chylothorax after Congenital Heart Surgery.
AB  - OBJECTIVE: Chylothorax complicates the postoperative course of patients after
      congenital heart surgery. Innominate vein thrombosis and stenosis have been
      associated with postoperative chylothorax. Revascularization and angioplasty can
      be accomplished using transcatheter techniques. We report our experience with
      this procedure for the management of postoperative chylothorax. DESIGN: This is a
      retrospective case series of patients who underwent catheter revascularization
      and/or angioplasty of the innominate vein following cardiac surgery at our
      institution from January 1, 2008 through April 9, 2014. SETTING: The
      cardiovascular intensive care unit and cardiac catheterization laboratory at the
      University of Alabama at Birmingham and Benjamin Russell Hospital for Children in
      Birmingham, Alabama were used as settings for the study. PATIENTS: Out of 112
      patients with postoperative chylothorax, 7 (6.3%) underwent transcatheter
      dilation of the innominate vein for occlusion/stenosis. The median age of the
      cohort was 1 month (15 days-6 years); median weight was 3 kg (2.7-22.2).
      Diagnosis was made a median 8 days (2-20) and persisted for a median of 24 days
      (9-44). Most patients failed medical management (low fat diet, nothing by mouth,
      and/or octreotide). RESULTS: Cardiac catheterization occurred at a median 9 days
      (2-29) after chylothorax diagnosis. Median chest tube output on the day prior to
      procedure was 63 (12-149) cc/kg/day and decreased to 23 (0-64) cc/kg/day 2 days
      postprocedure (P = .01). Effusions resolved in a median of 5 days (1-16). There
      were no clinical complications postcatheterization. All patients who have
      undergone repeat angiography have maintained patency of the innominate vein.
      There was no mortality. Complications from chylothorax included prolong
      hospitalization, hyponatremia, hypoproteinemia, coagulopathy, lymphopenia, and
      infection. CONCLUSIONS: Innominate vein occlusion and stenosis associated with
      chylous effusion are amenable to transcatheter revascularization and/or
      angioplasty, consistently leading to improvement, if not full resolution of
      chylothorax.

PMID- 25600287
TI  - Compensatory stabilizing role of surface mutations during the directed evolution
      of dienelactone hydrolase for enhanced activity.
AB  - Directed evolution is a common tool employed to generate enzymes suitable for
      industrial use. High thermal stability is often advantageous or even a
      requirement for biocatalysts, as such the evolution of protein stability is of
      practical as well as academic interest. Even when evolving enzymes for new or
      improved catalytic functions, stability is an important factor since it can limit
      the accumulation rate and number of desired active site mutations. Dienelactone
      hydrolase, a small monomeric protein, has been previously evolved via a three
      stage process to possess enhanced activity and specificity toward non
      physiological substrates. In addition to seven active site mutations there were
      three surface mutations that were thought to increase the stability of the enzyme
      and compensate for the destabilizing active site mutations. Here, the individual
      influence of the three surface mutations--Q110L, Y137C and N154D--on the thermal
      and chemical stability of DLH has been assessed. While the Q110L and N154D
      mutations improved the thermal stability, the influence of the Y137C mutation was
      more complex. Individually it was destabilizing both thermally and chemically,
      but when in the presence of the Q110L and N154D mutations its effect was
      neutralized in relation to thermal but not chemical stability. In the context of
      a directed evolution experiment, these compensatory surface mutations play
      important roles. However, our results show that detrimental mutations can arise,
      thus the simultaneous monitoring of stability changes while evolving enzymes for
      enhanced catalytic properties can be beneficial.

PMID- 25600288
TI  - Electrocapillarity and zero-frequency differential capacitance at the interface
      between mercury and ionic liquids measured using the pendant drop method.
AB  - The structure of ionic liquids (ILs) at the electrochemical IL|Hg interface has
      been studied using the pendant drop method. From the electrocapillarity
      (potential dependence of interfacial tension) differential capacitance (Cd) at
      zero frequency (in other words, static differential capacitance or differential
      capacitance in equilibrium) has been evaluated. The potential dependence of zero
      frequency Cd at the IL|Hg interface exhibits one or two local maxima near the
      potential of zero charge (Epzc), depending on the cation of the ILs. For 1-ethyl
      3-methylimidazolium tetrafluoroborate, an IL with the cation having a short alkyl
      chain, the Cdvs. potential curve has one local maximum whereas another IL, 1
      octyl-3-methylimidazolium tetrafluoroborate, with the cation having a long alkyl
      chain, shows two maxima. These behaviors of zero-frequency Cd agree with
      prediction by recent theoretical and simulation studies for the electrical double
      layer in ILs. At negative and positive potentials far from Epzc, the zero
      frequency Cd increases for both the ILs studied. The increase in zero-frequency
      Cd is attributable to the densification of ionic layers in the electrical double
      layer. 

PMID- 25600289
TI  - Insights into the trimeric HIV-1 envelope glycoprotein structure.
AB  - The HIV-1 envelope glycoprotein (Env) trimer is responsible for receptor
      recognition and viral fusion with CD4(+) T cells, and is the sole target for
      neutralizing antibodies. Thus, understanding its molecular architecture is of
      significant interest. However, the Env trimer has proved to be a challenging
      target for 3D structure determination. Recent electron microscopy (EM) and X-ray
      structures have at last enabled us to decipher the structural complexity and
      unique features of the Env trimer, and how it is recognized by an ever-expanding
      arsenal of potent broadly neutralizing antibodies. We describe our current
      knowledge of the Env trimer structure in the context of exciting recent
      developments in the identification and characterization of HIV broadly
      neutralizing antibodies. 

PMID- 25600290
TI  - Enabling online studies of conceptual relationships between medical terms:
      developing an efficient web platform.
AB  - BACKGROUND: The Unified Medical Language System (UMLS) contains many important
      ontologies in which terms are connected by semantic relations. For many studies
      on the relationships between biomedical concepts, the use of transitively
      associated information from ontologies and the UMLS has been shown to be
      effective. Although there are a few tools and methods available for extracting
      transitive relationships from the UMLS, they usually have major restrictions on
      the length of transitive relations or on the number of data sources. OBJECTIVE:
      Our goal was to design an efficient online platform that enables efficient
      studies on the conceptual relationships between any medical terms. METHODS: To
      overcome the restrictions of available methods and to facilitate studies on the
      conceptual relationships between medical terms, we developed a Web platform,
      onGrid, that supports efficient transitive queries and conceptual relationship
      studies using the UMLS. This framework uses the latest technique in converting
      natural language queries into UMLS concepts, performs efficient transitive
      queries, and visualizes the result paths. It also dynamically builds a
      relationship matrix for two sets of input biomedical terms. We are thus able to
      perform effective studies on conceptual relationships between medical terms based
      on their relationship matrix. RESULTS: The advantage of onGrid is that it can be
      applied to study any two sets of biomedical concept relations and the relations
      within one set of biomedical concepts. We use onGrid to study the disease-disease
      relationships in the Online Mendelian Inheritance in Man (OMIM). By
      crossvalidating our results with an external database, the Comparative
      Toxicogenomics Database (CTD), we demonstrated that onGrid is effective for the
      study of conceptual relationships between medical terms. CONCLUSIONS: onGrid is
      an efficient tool for querying the UMLS for transitive relations, studying the
      relationship between medical terms, and generating hypotheses.

PMID- 25600292
TI  - Functional genomics of PCOS: from GWAS to molecular mechanisms.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by
      increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a
      strong heritable component based on familial clustering and twin studies. Genome
      wide association studies (GWAS) identified several PCOS candidate loci including
      LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional
      roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A.
      We propose that these candidates comprise a hierarchical signaling network by
      which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream
      signaling cascades converge to regulate theca cell androgen biosynthesis. Future
      elucidation of the functional gene networks predicted by the PCOS GWAS will
      result in new diagnostic and therapeutic approaches for women with PCOS. 

PMID- 25600291
TI  - Resting-state EEG delta power is associated with psychological pain in adults
      with a history of depression.
AB  - Psychological pain is a prominent symptom of clinical depression. We asked if
      frontal alpha asymmetry, frontal EEG power, and frontal fractal dimension
      asymmetry predicted psychological pain in adults with a history of depression.
      Resting-state frontal EEG (F3/F4) was recorded while participants (N=35) sat
      upright with their eyes closed. Frontal delta power predicted psychological pain
      while controlling for depressive symptoms, with participants who exhibited less
      power experiencing greater psychological pain. Frontal fractal dimension
      asymmetry, a nonlinear measure of complexity, also predicted psychological pain,
      such that greater left than right complexity was associated with greater
      psychological pain. Frontal alpha asymmetry did not contribute unique variance to
      any regression model of psychological pain. As resting-state delta power is
      associated with the brain's default mode network, results suggest that the
      default mode network was less activated during high psychological pain. Findings
      are consistent with a state of arousal associated with psychological pain. 

PMID- 25600293
TI  - Loss of APD1 in yeast confers hydroxyurea sensitivity suppressed by Yap1p
      transcription factor.
AB  - Ferredoxins are iron-sulfur proteins that play important roles in electron
      transport and redox homeostasis. Yeast Apd1p is a novel member of the family of
      thioredoxin-like ferredoxins. In this study, we characterized the hydroxyurea
      (HU)-hypersensitive phenotype of apd1Delta cells. HU is an inhibitor of DNA
      synthesis, a cellular stressor and an anticancer agent. Although the loss of APD1
      did not influence cell proliferation or cell cycle progression, it resulted in HU
      sensitivity. This sensitivity was reverted in the presence of antioxidant N
      acetyl-cysteine, implicating a role for intracellular redox. Mutation of the iron
      binding motifs in Apd1p abrogated its ability to rescue HU sensitivity in
      apd1Delta cells. The iron-binding activity of Apd1p was verified by a color
      assay. By mass spectrometry two irons were found to be incorporated into one
      Apd1p protein molecule. Surprisingly, ribonucleotide reductase genes were not
      induced in apd1Delta cells and the HU sensitivity was unaffected when dNTP
      production was boosted. A suppressor screen was performed and the expression of
      stress-regulated transcription factor Yap1p was found to effectively rescue the
      HU sensitivity in apd1Delta cells. Taken together, our work identified Apd1p as a
      new ferredoxin which serves critical roles in cellular defense against HU. 

PMID- 25600294
TI  - Population pharmacokinetics and target attainment analysis of moxifloxacin in
      patients with diabetic foot infections.
AB  - The objective of this study was to provide a pharmacokinetic/pharmacodynamic
      (PK/PD) analysis of moxifloxacin in patients with diabetic foot infections (DFI).
      The plasma concentration-time courses were determined in 50 DFI patients on day 1
      and 3 after intravenous moxifloxacin 400 mg once-daily. A two-compartment
      population pharmacokinetic model was developed, identifying as covariates total
      body weight on central and peripheral volume of distribution (V1, V2) and ideal
      body weight on clearance (CL), respectively. For a 70 kg patient V1 was 68.1 L
      (interindividual variability, CV: 27.4%), V2 44.6 L, and CL 12.1 L/h (25.6%).
      Simulations were performed to calculate the probability of target attainment
      (PTA) for Gram-positive and Gram-negative pathogens with fAUC/MIC targets of >=30
      and >=100, respectively. PTA was 0.68-1 for susceptible (MIC <=0.5 mg/L according
      to EUCAST) Gram-positive, but <0.25 for Gram-negative pathogens with MIC >=0.25
      mg/L. With the exception of the first 24 hours of therapy, obesity affected PTA
      only marginally. Pharmacokinetic parameters in DFI patients were similar to those
      reported for healthy volunteers, indicating the appropriateness of the standard
      dose of moxifloxacin. Overall clinical efficacy has been shown previously, but
      PTA is limited in a subpopulation infected with formally susceptible Gram
      negative pathogens close to the EUCAST breakpoint. 

PMID- 25600296
TI  - A Swiss paradox? Higher income inequality of municipalities is associated with
      lower mortality in Switzerland.
AB  - It has long been surmised that income inequality within a society negatively
      affects public health. However, more recent studies suggest there is no
      association, especially when analyzing small areas. This study aimed to evaluate
      the effect of income inequality on mortality in Switzerland using the Gini index
      on municipality level. The study population included all individuals >30 years at
      the 2000 Swiss census (N = 4,689,545) living in 2,740 municipalities with 35.5
      million person-years of follow-up and 456,211 deaths over follow-up. Cox
      proportional hazard regression models were adjusted for age, gender, marital
      status, nationality, urbanization, and language region. Results were reported as
      hazard ratios (HR) with 95% confidence intervals. The mean Gini index across all
      municipalities was 0.377 (standard deviation 0.062, range 0.202-0.785). Larger
      cities, high-income municipalities and tourist areas had higher Gini indices.
      Higher income inequality was consistently associated with lower mortality risk,
      except for death from external causes. Adjusting for sex, marital status,
      nationality, urbanization and language region only slightly attenuated effects.
      In fully adjusted models, hazards of all-cause mortality by increasing Gini index
      quintile were HR = 0.99 (0.98-1.00), HR = 0.98 (0.97-0.99), HR = 0.95 (0.94
      0.96), HR = 0.91 (0.90-0.92) compared to the lowest quintile. The relationship of
      income inequality with mortality in Switzerland is contradictory to what has been
      found in other developed high-income countries. Our results challenge current
      beliefs about the effect of income inequality on mortality on small area level.
      Further investigation is required to expose the underlying relationship between
      income inequality and population health.

PMID- 25600298
TI  - Self-reported skin cancer is unreliable.

PMID- 25600299
TI  - Physicochemical and biological characterization of long-term operated sulfate
      reducing granular sludge in the SANI(r) process.
AB  - The SANI((r)) process (Sulfate reduction, Autotrophic denitrification and
      Nitrification Integrated) is a treatment system with low energy demands. The
      major bioreactor of this new technology is a sulfate-reducing up-flow sludge bed
      (SRUSB) that converts organics and provides electron donors for subsequent
      autotrophic denitrification. This research characterizes the granules inside the
      SRUSB, with the aim of improving its efficiency, maximizing its operational
      flexibility, and minimizing its footprint. The unique sulfate-reducing bacteria
      (SRB) granules serving in the SRUSB were found to increase the resilience and
      compactness of the SRUSB. The granules, with a compact and porous structure,
      showed high cohesion resisting breakage with a shear force G > 3400 s(-1). The
      hydrophobicity of the external surface of the mature granules remained stable at
      around 70% and acid volatile sulfide (AVS) accumulated at the bottom of the
      SRUSB. 16s rRNA gene analysis of the microbial communities revealed that
      Desulfobulbus (42.1%), Prosthecochloris (19%) and Trichococcus (12%) dominated
      the mature granular sludge. Fluorescence in situ hybridization (FISH) further
      showed that SRB organisms were located internally and then surrounded by non-SRB.
      According to the FISH results, the spatial distribution of extracellular
      polymeric substances (EPS) displayed protein and alpha-polysaccharides in the
      exterior and beta-polysaccharide in the core of the granules. Such biological
      structure suggests that each SRB granule acts as an efficient and independent
      unit, capable of achieving both fermentation and organic conversion. The present
      investigation sheds light on the physicochemical and biological characteristics
      of the SRB granulate. This information provides valuable information for scaling
      up the SANI((r)) process to treat real saline sewage in Hong Kong. 

PMID- 25600297
TI  - Polycyclic aromatic hydrocarbons and childhood asthma.
AB  - Asthma is the most common chronic illness in children living in developed
      countries and the leading cause of childhood hospitalization and school
      absenteeism. Prevalence rates of asthma are increasing and show disparities
      across gender, geographic regions, and ethnic/racial groups. Common risk factors
      for developing childhood asthma include exposure to tobacco smoke, previous
      allergic reactions, a family history of asthma, allergic rhinitis or eczema,
      living in an urban environment, obesity and lack of physical exercise, severe
      lower respiratory tract infections, and male gender. Asthma exacerbation in
      children can be triggered by a variety of factors, including allergens (e.g.,
      pollen, dust mites, and animal dander), viral and bacterial infections, exercise,
      and exposure to airway irritants. Recent studies have shown that exposure to
      polycyclic aromatic hydrocarbons (PAHs), a major component of fine particulate
      matter from combustion sources, is also associated with onset of asthma, and
      increasing asthmatic symptoms. In this paper, we review sources of childhood PAH
      exposure and the association between airborne PAH exposure and childhood asthma
      prevalence and exacerbation. 

PMID- 25600300
TI  - Post-treatment of biologically treated wastewater containing organic contaminants
      using a sequence of H2O2 based advanced oxidation processes: photolysis and
      catalytic wet oxidation.
AB  - In this paper the feasibility of a multi-barrier treatment (MBT) for the
      regeneration of synthetic industrial wastewater (SIWW) was evaluated. Industrial
      pollutants (orange II, phenol, 4-chlorophenol and phenanthrene) were added to the
      effluent of municipal wastewater treatment plant. The proposed MBT begins with a
      microfiltration membrane pretreatment (MF), followed by hydrogen peroxide
      photolysis (H2O2/UVC) and finishing, as a polishing step, with catalytic wet
      peroxide oxidation (CWPO) using granular activated carbon (GAC) at ambient
      conditions. During the microfiltration step (0.7 MUm) the decrease of suspended
      solids concentration, turbidity and Escherichia coli in treated water were 88, 94
      and 99%, respectively. Also, the effluent's transmittance (254 nm) was increased
      by 14.7%. Removal of more than 99.9% of all added pollutants, mineralization of
      63% of organic compounds and complete disinfection of total coliforms were
      reached during the H2O2/UVC treatment step (H2O2:TOC w/w ratio = 5 and an UVC
      average dose accumulated by wastewater 8.80 WUVC s cm(-2)). The power and
      efficiency of the lamp, the water transmittance and photoreactor geometry are
      taken into account and a new equation to estimate the accumulated dose in water
      is suggested. Remaining organic pollutants with a higher oxidation state of
      carbon atoms (+0.47) and toxic concentration of residual H2O2 were present in the
      effluent of the H2O2/UVC process. After 2.3 min of contact time with GAC at CWPO
      step, 90 and 100% of total organic carbon and residual H2O2 were removed,
      respectively. Also, the wastewater toxicity was studied using Vibrio fischeri and
      Sparus aurata larvae. The MBT operational and maintenance costs (O&M) was
      estimated to be 0.59 ? m(-3). 

PMID- 25600301
TI  - Membrane distillation combined with an anaerobic moving bed biofilm reactor for
      treating municipal wastewater.
AB  - A fermentative strategy with an anaerobic moving bed biofilm reactor (AMBBR) was
      used for the treatment of domestic wastewater. The feasibility of using a
      membrane separation technique for post-treatment of anaerobic bio-effluent was
      evaluated with emphasis on employing a membrane distillation (MD). Three
      different hydrophobic 0.2 MUm membranes made of polytetrafluoroethylene (PTFE),
      polyvinylidene fluoride (PVDF), and polypropylene (PP) were examined in this
      study. The initial permeate flux of the membranes ranged from 2.5 to 6.3 L m(-2)
      h(-1) when treating AMBBR effluent at a temperature difference between the feed
      and permeate streams of 20  degrees C, with the permeate flux increasing in the
      order PP < PVDF < PTFE. The permeate flux of the PTFE membrane gradually
      decreased to 84% of the initial flux after the 45 h run for distillation, while a
      flux decline in MD with either the PVDF or PP membrane was not found under the
      identical distillation conditions. During long-term distillation with the PVDF
      membrane, total phosphorus was completely rejected and >98% rejection of
      dissolved organic carbon was also achieved. The characterization of wastewater
      effluent organic matter (EfOM) using an innovative suite of analytical tools
      verified that almost all of the EfOM was rejected via the PVDF MD treatment. 

PMID- 25600295
TI  - Broad targeting of angiogenesis for cancer prevention and therapy.
AB  - Deregulation of angiogenesis--the growth of new blood vessels from an existing
      vasculature--is a main driving force in many severe human diseases including
      cancer. As such, tumor angiogenesis is important for delivering oxygen and
      nutrients to growing tumors, and therefore considered an essential pathologic
      feature of cancer, while also playing a key role in enabling other aspects of
      tumor pathology such as metabolic deregulation and tumor
      dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a
      clinical anti-cancer strategy in line with chemotherapy, radiotherapy and
      surgery, which underscore the critical importance of the angiogenic switch during
      early tumor development. Unfortunately the clinically approved anti-angiogenic
      drugs in use today are only effective in a subset of the patients, and many who
      initially respond develop resistance over time. Also, some of the anti-angiogenic
      drugs are toxic and it would be of great importance to identify alternative
      compounds, which could overcome these drawbacks and limitations of the currently
      available therapy. Finding "the most important target" may, however, prove a very
      challenging approach as the tumor environment is highly diverse, consisting of
      many different cell types, all of which may contribute to tumor angiogenesis.
      Furthermore, the tumor cells themselves are genetically unstable, leading to a
      progressive increase in the number of different angiogenic factors produced as
      the cancer progresses to advanced stages. As an alternative approach to targeted
      therapy, options to broadly interfere with angiogenic signals by a mixture of non
      toxic natural compound with pleiotropic actions were viewed by this team as an
      opportunity to develop a complementary anti-angiogenesis treatment option. As a
      part of the "Halifax Project" within the "Getting to know cancer" framework, we
      have here, based on a thorough review of the literature, identified 10 important
      aspects of tumor angiogenesis and the pathological tumor vasculature which would
      be well suited as targets for anti-angiogenic therapy: (1) endothelial cell
      migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3)
      hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6)
      poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting
      inflammation, (9) tumor promoting fibroblasts and (10) tumor cell
      metabolism/acidosis. Following this analysis, we scrutinized the available
      literature on broadly acting anti-angiogenic natural products, with a focus on
      finding qualitative information on phytochemicals which could inhibit these
      targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic
      acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate,
      (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10)
      resveratrol. We suggest that these plant-derived compounds could be combined to
      constitute a broader acting and more effective inhibitory cocktail at doses that
      would not be likely to cause excessive toxicity. All the targets and
      phytochemical approaches were further cross-validated against their effects on
      other essential tumorigenic pathways (based on the "hallmarks" of cancer) in
      order to discover possible synergies or potentially harmful interactions, and
      were found to generally also have positive involvement in/effects on these other
      aspects of tumor biology. The aim is that this discussion could lead to the
      selection of combinations of such anti-angiogenic compounds which could be used
      in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced
      toxicity and circumvention of single-agent anti-angiogenic resistance, as well as
      for possible use in primary or secondary cancer prevention strategies.

PMID- 25600302
TI  - Functional analysis of Girardia tigrina transcriptome seeds pipeline for
      anthelmintic target discovery.
AB  - BACKGROUND: Neglected diseases caused by helminth infections impose a massive
      hindrance to progress in the developing world. While basic research on parasitic
      flatworms (platyhelminths) continues to expand, researchers have yet to broadly
      adopt a free-living model to complement the study of these important parasites.
      METHODS: We report the high-coverage sequencing (RNA-Seq) and assembly of the
      transcriptome of the planarian Girardia tigrina across a set of dynamic
      conditions. The assembly was annotated and extensive orthology analysis was used
      to seed a pipeline for the rational prioritization and validation of putative
      anthelmintic targets. A small number of targets conserved between parasitic and
      free-living flatworms were comparatively interrogated. RESULTS: 240 million
      paired-end reads were assembled de novo to produce a strictly filtered predicted
      proteome consisting of over 22,000 proteins. Gene Ontology annotations were
      extended to 16,467 proteins. 2,693 sequences were identified in orthology groups
      spanning flukes, tapeworms and planaria, with 441 highlighted as belonging to
      druggable protein families. Chemical inhibitors were used on three targets in
      pharmacological screens using both planaria and schistosomula, revealing distinct
      motility phenotypes that were shown to correlate with planarian RNAi phenotypes.
      CONCLUSIONS: This work provides the first comprehensive and annotated sequence
      resource for the model planarian G. tigrina, alongside a prioritized list of
      candidate drug targets conserved among parasitic and free-living flatworms. As
      proof of principle, we show that a simple RNAi and pharmacology pipeline in the
      more convenient planarian model system can inform parasite biology and serve as
      an efficient screening tool for the identification of lucrative anthelmintic
      targets.

PMID- 25600303
TI  - UK foundation-year 1 doctors--a survey uncovering infrequent theater experience
      regardless of time, place, or surgical specialty.
AB  - INTRODUCTION: Doctors in the United Kingdom are expected to choose a broad career
      path after approximately 16 months of finishing medical school. We aim to
      investigate how much surgical exposure foundation-year (FY)1 doctors would have
      by the end of their first year after finishing medical school and whether this is
      sufficient to make an informed decision on a career in surgery. METHOD: Cross
      sectional survey via a 10-part questionnaire sent to 1341 FY1 doctors at the end
      of their first clinical year across secondary and tertiary hospitals within 9
      foundation schools in the United Kingdom. RESULTS: A total of 389 FY1 doctors
      responded. More than half (52.2%) of the FY1 doctors were unable to attend
      theater more than 5 times during their rotation. Length of surgical rotation,
      surgical specialty, type of hospital, and prior interest in surgery had no
      significant effect on theater attendance (p > 0.05). More than half (50.9%) of
      the FY1 doctors did not feel like they had had sufficient experience to make an
      informed decision about a career in surgery. DISCUSSION: Poor theater attendance
      is common among FY1 doctors, which may lead to ill-informed specialty career
      decisions. The Modernising Medical Careers program and European Working Time
      Directive are likely contributing to this lack of exposure. Protected and logged
      theater sessions for all FY1 doctors could ensure sufficient exposure. New
      initiatives need to be employed to increase surgical exposure among FY1 doctors
      to ensure that specialty choices in their second FY are informed ones. The
      proposed changes to the United Kingdom's junior doctor's training in the "Shape
      of Training" report may mean that changes in exposure in the early years are even
      more pertinent.

PMID- 25600304
TI  - Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased
      time of glucose in target with a wearable artificial pancreas using modular model
      predictive control in adults with type 1 diabetes.
AB  - AIMS: To test in an outpatient setting the safety and efficacy of continuous
      subcutaneous insulin infusion (CSII) driven by a modular model predictive control
      (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement.
      METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized
      outpatient 42-h experiment that included two evening meals and overnight periods
      (in short, dinner & night periods). CSII was patient-driven during dinner & night
      period 1 and MMPC-driven during dinner&night period 2. The study was conducted in
      hotels, where patients could move around freely. A CGM system (G4 Platinum;
      Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche
      Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based
      platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA,
      USA) during both periods. RESULTS: A significantly lower percentage of time spent
      with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1:
      1.96 +/- 4.56% vs 12.76 +/- 15.84% (mean +/- standard deviation, p < 0.01),
      together with a greater percentage of time spent in the 3.9-10 mmol/l target
      range: 83.56 +/- 14.02% vs 62.43 +/- 29.03% (p = 0.04). In addition, restricting
      the analysis to the overnight phases, a lower percentage of time spent with
      glucose levels <3.9 mmol/l (1.92 +/- 4.89% vs 12.7 +/- 19.75%; p = 0.03) was
      combined with a greater percentage of time spent in 3.9-10 mmol/l target range in
      period 2 compared with period 1 (92.16 +/- 8.03% vs 63.97 +/- 2.73%; p = 0.01).
      Average glucose levels were similar during both periods. CONCLUSIONS: The results
      suggest that MMPC managed by a wearable system is safe and effective during
      evening meal and overnight. Its sustained use during this period is currently
      being tested in an ongoing randomized 2-month study.

PMID- 25600305
TI  - Implementing elements of a context-adapted chronic care model to improve first
      line diabetes care: effects on assessment of chronic illness care and glycaemic
      control among people with diabetes enrolled to the First-Line Diabetes Care
      (FiLDCare) Project in the Northern Philippines.
AB  - Aim The purpose of this study was to investigate the effects of implementing
      elements of a context-adapted chronic disease-care model (CACCM) in two local
      government primary healthcare units of a non-highly urbanized city and a rural
      municipality in the Philippines on Patients' Assessment of Chronic Illness Care
      (PACIC) and glycaemic control (HbA1c) of people with diabetes. BACKGROUND: Low-to
      middle income countries like the Philippines are beset with rising prevalence of
      chronic conditions but their healthcare systems are still acute disease oriented.
      Attention towards improving care for chronic conditions particularly in primary
      healthcare is imperative and ways by which this can be done amidst resource
      constraints need to be explored. METHODS: A chronic care model was adapted based
      on the context of the Philippines. Selected elements (community sensitization,
      decision support, minor re-organization of health services, health service
      delivery-system re-design, and self-management education and support) were
      implemented. PACIC and HbA1c were measured before and one year after the start of
      implementation. Findings The improvements in the PACIC (median, from 3.2 to 3.5)
      as well as in four of the five subsets of the PACIC were statistically
      significant (P-values: PACIC=0.009; 'patient activation'=0.026; 'goal
      setting'=0.017; 'problem solving'<0.001; 'follow-up'<0.001). The decrease in
      HbA1c (median, from 7.7% to 6.9%) and the level of diabetes control of the
      project participants (increase of optimally controlled diabetes from 37.2% to
      50.6%) were likewise significant (P<0.000 and P=0.014). A significantly higher
      rating of the post-implementation PACIC subsets 'problem solving' (P=0.027) and
      'follow-up' (P=0.025) was noted among those participants whose HbA1c improved.
      The quality of chronic care in general and primary diabetes care in particular
      may be improved, as measured through the PACIC and glycaemic control, in resource
      constrained settings applying selected elements of a CACCM and without causing
      much strain on an already-burdened healthcare system.

PMID- 25600306
TI  - Sperm protein 17 and AKAP-associated sperm protein cancer/testis antigens are
      expressed in ciliated hepatic foregut cysts.
AB  - AIMS: Ciliated hepatic foregut cysts (CHFCs) are retained benign lesions of the
      liver. However, a case of squamous cell metaplasia and five cases of squamous
      cell carcinoma arising from a CHFC have been described. The potential of
      malignant transformation makes the identification of new biomarkers necessary. As
      the cancer/testis antigen sperm protein 17 (Sp17) has been detected in oral and
      oesophageal squamous cell carcinomas, the aim of this study was to investigate
      the expression of Sp17 and AKAP-associated sperm protein (ASP), which has a
      shared N-terminal sequence with Sp17, in four surgically resected CHFCs. METHODS
      AND RESULTS: CHFC specimens were taken from two patients who attended the Medical
      College of Wisconsin, Milwaukee, USA and two patients who attended the Fundacion
      Jimenez Diaz, Madrid, Spain. CHFCs were found to be immunopositive for Sp17 and
      ASP. Both proteins were localized to the cytoplasm of ciliated cells lining the
      cysts, and their cilia. Confocal microscopy demonstrated that Sp17 and ASP
      overlapped in the same region of the cell. CONCLUSION: Sp17 and ASP cancer/testis
      antigens were found in ciliated cells of four CHFCs. Further characterization of
      Sp17 and ASP in patients with CHFCs may provide significant clues for
      understanding the molecular mechanisms underlying their predisposition to develop
      squamous cell carcinomas.

PMID- 25600307
TI  - Sacral anterior root stimulation improves bowel function in subjects with spinal
      cord injury.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the long-term effect
      of the sacral anterior root stimulator (SARS) on neurogenic bowel dysfunction in
      a large, well defined spinal cord injury (SCI) cohort. SETTING: Department of
      Neuro-Urology, Bad Wildungen, Germany. METHODS: Subjects undergone surgery at for
      SARS-SDAF (sacral deafferentation) between September 1986 and July 2011 (n=587)
      answered a questionnaire. In total, 277 SARS subjects were available for the
      baseline (recall) and follow-up comparison. RESULTS: Median age was 49 years
      (range: 19-80), time from SCI to surgery was 10 years (range: 0-49) and from
      surgery to follow-up 13 (range: 1-25). Of the responders 73% used SARS for bowel
      emptying. On visual analog scale (VAS) ranging from 0-10 (best), satisfaction
      with SARS was 10. Baseline and follow-up comparison showed a decline in the
      median VAS score 0-10 (worst) for bowel symptoms from 6 (range: 4-8) to 4 (range:
      2-6), P<0.0001; median neurogenic bowel dysfunction score from 17 (range: 11-2)
      to 11 (range: 9-15), P<0.0001; median St Marks score from 4 (range: 0-7) to 4
      (range: 0-5), P=0.01; and median Cleveland constipation score from 7 (range: 6
      10) to 6 (range: 4-8), P<0.0001. Use of suppositories, digital evacuation and
      mini enema and subjects totally dependent on assistance during defecation were
      significantly lower after SARS. CONCLUSIONS: The SARS has the potential to be one
      of the few treatment methods targeting multiple organ dysfunctions following SCI.

PMID- 25600308
TI  - The efficiency of orthotic interventions on energy consumption in paraplegic
      patients: a literature review.
AB  - Study design:This is a systematic literature review.Objectives:Different types of
      orthoses have been developed to enable and facilitate ambulation in individuals
      with paraplegia. However, their effect on energy consumption while ambulating is
      not clear. The objective of this review was to compare the energy expenditure
      required to walk with these devices.Methods:Using the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) method, and based on selected
      keywords and their composition according to the Population Intervention
      Comparison Outcome (PICO) method, a search was performed in Science Direct,
      Google Scholar, Scopus, Web of Knowledge and PubMed databases. The searches were
      restricted to papers published in the English language and were conducted during
      February 2014; the last access to the database was on 25 February 2014. A total
      of 24 articles were chosen for final evaluation.Results:Hybrid orthoses reduce
      energy consumption compared with mechanical orthoses when used for walking by
      paraplegic patients. The isocentric reciprocating gait orthosis has been shown to
      be more effective than other reciprocating orthoses in reducing energy
      consumption. Energy consumption when walking with powered orthoses (PO) and
      hybrid orthoses was also reduced compared with when walking with conventional
      orthoses.Conclusions:The hybrid orthoses and PO could be effective alternatives
      in rehabilitation for spinal cord injury patients to help improve the energy
      consumption.Spinal Cord advance online publication, 20 January 2015;
      doi:10.1038/sc.2014.227.

PMID- 25600309
TI  - Influence of wheelchair footrest height on ischial tuberosity pressure in
      individuals with paraplegia.
AB  - OBJECTIVE: To describe the effect of wheelchair footrest height on sitting
      pressures in persons with paraplegia. METHODS: Seventeen manual wheelchair users
      with paraplegia underwent a seat pressure examination while footrests were
      elevated from the initial position with the thighs parallel to the seat (p0), by
      10% (position p10) and by 20% of the fibula length (position p20). We analyzed
      average pressure (AP), the contact surface of the body with the seat (CS),
      pressures on the ischial tuberosities-left (LIP) and right (RIP)--and average
      pressure on both ischial tuberosities (AIP). RESULTS: A gradual increase in
      footrest elevation was accompanied by significant increases in AP (p0: 57.24+/
      14.31; p10: 60.65+/-14.85; p20: 62+/-15.3 mm Hg; Kendall coefficient of
      concordance W=0.962), AIP (p0: 159.35+/-54.95; p10: 176.35+/-53.3; p20: 184.26+/
      54.09 mm Hg; W=0.896), LIP (p0: 165.24+/-54.05; p10: 183+/-52.08; p20: 193.18+/
      56.32 mm Hg; W=0.751) and RIP (p0: 153.71+/-71.23; p10: 167.35+/-72.19; p20:
      175.35+/-70.84 mm Hg; W=0.524) and a significant decrease in CS (p0: 1218.2+/
      100.8; p10: 1131.8+/-134.6; p20: 1065+/-142.6 cm(2); W=0.985). There was a
      moderate correlation between the relative increase in LIP and RIP between p0 and
      p10, and between p10 and p20 (Pearson's correlation coefficient for LIP r=0.66;
      P=0.04, for RIP r=0.77; P=0.003), and a high correlation between relative changes
      in AIP (r=0.87; P<0.0001). CONCLUSION: Wheelchair footrest elevation caused a
      steady rise in AIP; however, left to right side pressure differences changed
      variably, suggesting that the risk of pressure ulcers may increase
      disproportionately with footrest elevation.

PMID- 25600310
TI  - Quantitative magnetic resonance imaging in a naturally occurring canine model of
      spinal cord injury.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To analyze magnetic
      resonance imaging (MRI) evaluator agreement in dogs with spinal cord injury (SCI)
      caused by intervertebral disk herniation (IVDH) using semiautomated and manual
      lesion segmentation and to analyze the associations between MRI and functional
      outcome. SETTING: United States of America. METHODS: T2-weighted MRIs from dogs
      with SCI resulting from thoracolumbar IVDH were identified from a database.
      Evaluators categorized MRIs on the basis of the presence or absence of a T2
      hyperintense spinal cord lesion in axial and sagittal images. A semiautomated
      segmentation algorithm was developed and used to estimate the lesion volume.
      Agreement between evaluators and between semiautomated and manual segmentation
      was analyzed. The relationships of qualitative and quantitative MRIs with
      behavioral functional outcome were analyzed. RESULTS: Axial images more commonly
      depicted lesions compared with sagittal images. Lesions in axial images had more
      consistent associations with functional outcome compared with sagittal images.
      There was imperfect qualitative agreement, and lesion volume estimation was
      imprecise. However, there was improved precision using semiautomated segmentation
      compared with manual segmentation. CONCLUSION: Lesion volume estimation in dogs
      with naturally occurring SCI caused by IVDH is challenging, and axial images have
      important advantages compared with sagittal images. The semiautomated
      segmentation algorithm described herein shows promise but may require further
      refinement.

PMID- 25600311
TI  - Intravenous immune globulin: another disappointing treatment for recurrent
      pregnancy loss.

PMID- 25600312
TI  - Method validation and reference range values for a peripheral blood
      immunophenotyping assay in non-human primates.
AB  - A peripheral blood immunophenotyping assay was developed and validated for
      determination of total T-lymphocytes, helper T-lymphocytes, cytotoxic T
      lymphocytes, B-lymphocytes, and natural killer cells in cynomolgus monkeys.
      Validation parameters included assessment of precision, linearity, antibody
      optimization, stability of peripheral blood samples, and stability of fixed
      immunophenotyping samples. Total lymphocyte populations were determined using a
      heterogeneous lymphocyte gating strategy consisting of CD45 fluorescent staining
      and side-scatter demarcation. Relative lymphocyte subset values were determined
      using antigen-specific gating strategies. Absolute subset concentrations for each
      lymphocyte subset were subsequently determined using a dual-platform methodology
      wherein relative lymphocyte subset values (via flow cytometry analyses) were
      multiplied by the absolute total lymphocyte (via hematology analyses) values.
      Reference ranges are presented for cynomolgus monkey, rhesus monkey, and baboon.
      Additional 1-year longitudinal immunophenotyping values are presented for the
      cynomolgus monkey. The method validation and reference ranges presented in this
      research provide a robust analytical methodology for determination of peripheral
      blood lymphocyte subsets in various non-human primate species. 

PMID- 25600313
TI  - Site-specific association between distal aortic pulse wave velocity and
      peripheral arterial stenosis severity: a prospective cardiovascular magnetic
      resonance study.
AB  - BACKGROUND: Vascular disease expression in one location may not be representative
      for disease severity in other vascular territories, however, strong correlation
      between disease expression and severity within the same vascular segment may be
      expected. Therefore, we hypothesized that aortic stiffening is more strongly
      associated with disease expression in a vascular territory directly linked to
      that aortic segment rather than in a more remote segment. We prospectively
      compared the association between aortic wall stiffness, expressed by pulse wave
      velocity (PWV), sampled in the distal aorta, with the severity of peripheral
      arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled
      in remote vascular territories such as PWV in the proximal aorta and the
      normalized wall index (NWI), representing the vessel wall thickness, of the left
      common carotid artery. METHODS: Forty-two patients (23 men; mean age 64+/-10
      years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the
      proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA)
      and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD.
      Strength of associations between aortic stiffness, carotid NWI and peripheral
      vascular stenosis grade were assessed and evaluated with multiple linear
      regression. RESULTS: Stenosis severity correlated well with PWV in the distal
      aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser
      extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18).
      Carotid NWI was not associated with peripheral stenosis severity (rP=0.17,
      p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor
      in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and
      distal aortic PWV remained statistically significant after correction for age and
      gender. CONCLUSIONS: Distal aortic wall stiffness is more directly related to
      peripheral arterial stenosis severity than markers from more remote vascular
      territories such as proximal aortic wall stiffness or carotid arterial wall
      thickness. Site-specific evaluation of vascular disease may be required for full
      vascular risk estimation.

PMID- 25600314
TI  - Correlations between MDM2 gene SNP309 polymorphism and susceptibility to
      leukemia.
AB  - BACKGROUND: The objective of this study was to perform a systematic review of
      correlations between the single-nucleotide polymorphism at nucleotide 309 (single
      nucleotide polymorphism, SNP309) in the murine double-minute 2 (MDM2) gene
      promoter and susceptibility to leukemia. MATERIAL/METHODS: We performed a
      computer search of relevant case-control studies published from January 1990 to
      Jan 2014 in databases such as Ovid, EBSCO, PubMed, CNKI, CBMDISC, VIP, and
      WanFang Data. The literature was screened based on inclusion and exclusion
      criteria. The data were retrieved, and the quality of the methodology used in the
      studies was evaluated. A meta-analysis was performed by calculating the combined
      odds ratios (OR) and 95% confidence intervals (CI) using RevMan 5.0 and Stata
      10.0 software. Sensitivity was analyzed and publication bias was assessed.
      RESULTS: A total of ten case-control studies from nine research papers were
      selected in this study, which included 1889 cases and 5707 controls. Meta
      analysis showed that people who carried the G allele had increased susceptibility
      to leukemia compared to people who carried the T allele [OR=1.24, 95% CI (1.06,
      1.45), P=0.007]. In a recessive model, the GG homozygotic population had a higher
      risk of leukemia than the heterozygotic GT+TT population [OR=1.47, 95% CI (1.11,
      1.96), P=0.008]. We did not find significant difference in a dominant model
      [GG+GT vs. TT: OR=1.22, 95% CI (0.98, 1.52), P=0.07]. Publication bias was not
      significant. CONCLUSIONS: SNP309 polymorphism in the MDM2 gene is associated with
      susceptibility to leukemia. The G allele may be a risk factor for leukemia.

PMID- 25600315
TI  - Stability of Le Fort I maxillary inferior repositioning surgery with rigid
      internal fixation: a systematic review.
AB  - The aim of this study was to evaluate the stability of Le Fort I maxillary
      inferior repositioning surgery in patients with a vertical maxillary deficiency
      at least 6 months after surgery. The electronic databases were searched to
      identify all articles reporting the long-term effects of one-piece maxillary
      inferior repositioning with rigid fixation. Methodological quality was evaluated
      according to 15 criteria related to study design, measurements, and statistical
      analysis. Two articles were identified, with a total of 22 patients. The maxilla
      was repositioned inferiorly from a mean 3.2 to 4.5mm in the anterior part and
      from a mean 0.1 to 1.8mm in the posterior part. At 6 months post-treatment,
      absolute relapse of a mean 1.6mm was measured for the anterior part of the
      maxilla and 0.3mm for the posterior part of the maxilla. The stability of
      maxillary inferior repositioning surgery could not be confirmed due to the small
      sample size, unclear diagnosis, and potential confounding factors. 

PMID- 25600316
TI  - Photo-responsive reversible assembly of gold nanoparticles coated with
      pillar[5]arenes.
AB  - Organic solvent soluble gold nanoparticles based on pillar[5]arenes were prepared
      for the first time. They can reversibly aggregate and disassemble based on
      photo[4+4] cycloaddition of anthracene and can be used as recyclable catalysts. 

PMID- 25600317
TI  - Si=P double bonds: experimental and theoretical study of an NHC-stabilized
      phosphasilenylidene.
AB  - An experimental and theoretical study of the first compound featuring a Si=P bond
      to a two-coordinate silicon atom is reported. The NHC-stabilized
      phosphasilenylidene (IDipp)Si=PMes* (IDipp=1,3-bis(2,6
      diisopropylphenyl)imidazolin-2-ylidene, Mes*=2,4,6-tBu3 C6 H2 ) was prepared by
      SiMe3 Cl elimination from SiCl2 (IDipp) and LiP(Mes*)SiMe3 and characterized by X
      ray crystallography, NMR spectroscopy, cyclic voltammetry, and UV/Vis
      spectroscopy. It has a planar trans-bent geometry with a short Si=P distance of
      2.1188(7)A and acute bonding angles at Si (96.90(6) degrees ) and P (95.38(6)
      degrees ). The bonding parameters indicate the presence of a Si=P bond with a
      lone electron pair of high s-character at Si and P, in agreement with natural
      bond orbital (NBO) analysis. Comparative cyclic voltammetric and UV/Vis
      spectroscopic experiments of this compound, the disilicon(0) compound
      (IDipp)Si=Si(IDipp), and the diphosphene Mes*P=PMes* reveal, in combination with
      quantum chemical calculations, the isolobal relationship of the three double-bond
      systems.

PMID- 25600318
TI  - Seroprevalence and risk factors associated with within-flock transmission of
      Leptospira interrogans in transhumant farming systems in Mexico.
AB  - A number of recent reports emphasize the risk of zoonotic diseases and the high
      degree of prevalence of asymptomatic animals infected with Leptospira
      interrogans. This report sought to assess the prevalence of antibodies to certain
      serovars of L. interrogans, and to describe the association between
      seropositivity and risk factors associated with within-flock transmission in a
      mountainous region of Mexico. Overall seroprevalence to L. interrogans was 54.5%
      (95% confidence interval 48.3-60.7); the most frequent serovar was
      Icterohaemorrhagiae. The accumulation of placentas and fetuses at a site close to
      lambing paddocks can play a significant role as a risk factor for within-flock
      transmission of L. interrogans in transhumant farming systems in the municipality
      of Xalatlaco. The high prevalence of L. interrogans antibodies supports the
      hypothesis that natural foci of this zoonosis are present in sheep flocks in this
      area. These findings emphasize the need for planning and implementation of
      control programmes for ovine leptospirosis in Mexico and elsewhere. 

PMID- 25600319
TI  - The role of attached phase soil and sediment organic matter physicochemical
      properties on fullerene (nC60) attachment.
AB  - Attached phase soil and sediment organic matter is ubiquitous in the subsurface
      environment, with a tendency to strongly sorb contaminants, and therefore it may
      play an important role in contaminant transport. In this study, the deposition of
      C60 nanoparticles onto attached phase Harpeth Humic Acid and Harpeth Fulvic Acid
      (HHA and HFA) is explored by using a quartz crystal microbalance with dissipation
      monitoring and systematically varying thermal energy. By comparing the C60
      attachment onto HHA and HFA surfaces to that of bare silica and DLVO predictions,
      we find that the HHA and HFA layers hinder attachment at low temperatures, while
      HHA enhances attachment at higher temperatures. Based on thermal characterization
      of the HHA and HFA layers compared to the corresponding attachment trends, the
      attachment efficiency is strongly correlated with hydration of the layer.
      Possible mechanisms explaining this phenomenon include water-assisted disruption
      of polar SOM contacts and hydration-induced swelling of the AP-SOM matrix. Since
      humic substances typically dominate subsurface organic matter, these results may
      prove crucial to understanding the complex interactions of engineered
      nanomaterials in both the natural and engineered environment.

PMID- 25600320
TI  - Rapid oxidation and immobilization of arsenic by contact glow discharge plasma in
      acidic solution.
AB  - Arsenic is a priority pollutant in aquatic ecosystem and therefore the
      remediation of arsenic-bearing wastewater is an important environmental issue.
      This study unprecedentedly reported simultaneous oxidation of As(III) and
      immobilization of arsenic can be achieved using contact glow discharge process
      (CGDP). CGDP with thinner anodic wire and higher energy input were beneficial for
      higher As(V) production efficiency. Adding Fe(II) in CGDP system significantly
      enhanced the oxidation rate of As(III) due to the generations of additional OH
      and Fe(IV) species, accompanied with which arsenic can be simultaneously
      immobilized in one process. Arsenic immobilization can be favorably obtained at
      solution pH in the range of 4.0-6.0 and Fe(II) concentration from 250 to 1000
      MUM. The presence of organics (i.e., oxalic acid, ethanol and phenol) retarded
      the arsenic immobilization by scavenging OH or complexing Fe(III) in aqueous
      solution. On the basis of these results, a mechanism was proposed that the formed
      ionic As(V) rapidly coprecipitated with Fe(III) ions or was adsorbed on the
      ferric oxyhydroxides with the formation of amorphous ferric arsenate-bearing
      ferric oxyhydroxides. This CGDP-Fenton system was of great interest for
      engineered systems concerned with the remediation of arsenic containing
      wastewater.

PMID- 25600321
TI  - A time series analysis of multiple ambient pollutants to investigate the
      underlying air pollution dynamics and interactions.
AB  - Understanding the temporal dynamics and interactions of particulate matter (PM)
      concentration and composition is important for air quality control. This paper
      applied a dynamic factor analysis method (DFA) to reveal the underlying
      mechanisms of nonstationary variations in twelve ambient concentrations of
      aerosols and gaseous pollutants, and the associations with meteorological
      factors. This approach can consider the uncertainties and temporal dependences of
      time series data. The common trends of the yearlong and three selected diurnal
      variations were obtained to characterize the dominant processes occurring in
      general and specific scenarios in Taipei during 2009 (i.e., during Asian dust
      storm (ADS) events, rainfall, and under normal conditions). The results revealed
      the two distinct yearlong NOx transformation processes, and demonstrated that
      traffic emissions and photochemical reactions both critically influence diurnal
      variation, depending upon meteorological conditions. During an ADS event,
      transboundary transport and distinct weather conditions both influenced the
      temporal pattern of identified common trends. This study shows the DFA method can
      effectively extract meaningful latent processes of time series data and provide
      insights of the dominant associations and interactions in the complex air
      pollution processes. 

PMID- 25600322
TI  - Solid-liquid separation method governs the in vitro bioaccessibility of metals in
      contaminated soil-like test materials.
AB  - An in vitro gastrointestinal model was used to explore the role of solid-liquid
      separation method on the bioaccessibility of trace elements in a smelter-impacted
      soil (NIST-2711) from Helena, MT and a mine overburden from an open-pit gold and
      silver mine in Mount Nansen, YK (YK-OVB). Separation methods studied included
      centrifugation (5,000 g, 12,000 g), syringe microfiltration (0.45 MUm), and
      ultrafiltration (1,000 kDa, 50 kDa, 30 kDa, 10 kDa, 3 kDa). Results indicated
      that the use of syringe microfiltration generally yields the same
      bioaccessibility as the use of centrifugation and that the speed of
      centrifugation does not typically affect metal bioaccessibility. However,
      ultrafiltration consistently yields a significantly lower bioaccessibility than
      the use of centrifugation and syringe microfiltration. There are rarely any
      differences between bioaccessibility estimates generated using a low-resistance
      (1,000 kDa) and a high-resistance (3 kDa) ultrafiltration membrane; therefore,
      under the in vitro gastrointestinal conditions modeled herein, negligible
      quantities of trace elements are complexed to small molecules between 3 and 1,000
      kDa. The primary exceptions to these trends were observed for Pb in NIST-2711
      (5,000 g>12,000 g>0.45 MUm>ultrafiltration) and for Tl in NIST-2711 and YK-OVB
      (5000 g~12,000 g>0.45 MUm>ultrafiltration). These results provide valuable
      information to researchers attempting to expand the use of in vitro
      bioaccessibility beyond soil Pb and As.

PMID- 25600323
TI  - Urinary polycyclic aromatic hydrocarbon metabolites levels in a representative
      sample of the Spanish adult population: The BIOAMBIENT.ES project.
AB  - In 2009, the Spanish Ministry of Agriculture, Food and Environment promoted the
      BIOAMBIENT.ES project, a Human Biomonitoring program on the national scale to
      estimate reference levels of environmental pollutants on a representative sample
      of the Spanish adults. The present study focuses on polycyclic aromatic
      hydrocarbons (PAHs). The urinary metabolites 1-hydroxypyrene, 1-,2-,3-,4- and 9
      hydroxyphenanthrene and 3-hydroxybenzo[a]pyrene were selected as indicators of
      PAH exposure. Urine samples from 957 subjects (16-65 years old) were collected
      during year 2009-2010. Geometric mean and 95th percentile for 1-hydroxypyrene in
      MUg g(-1) creatinine were 0.117 (non-smoker: 0.079, smokers: 0.184) and 0.67 MUg
      g(-1) creatinine (non-smokers: 0.31, smokers: 0.69) respectively. GM and 95th
      percentile for sum of hydroxyphenanthrenes in MUg g(-1) creatinine were 0.130
      (non-smokers: 0.089, smokers: 0.317) and 1.29 (non-smokers: 0.71, smokers: 1.51)
      respectively. 3-Hydroxybenzo[a]pyrene was below the limit of quantitation (0.05
      MUg L(-1)) in all cases. Significant differences (p<0.05) regarding smokers and
      non-smokers, coal and wood heating, body mass index and second hand smoke were
      found, while other variables like gender, age, or diet showed no significant
      association. The geographical distribution of the metabolites showed higher
      levels in people who lived in the north and northwest of Spain. The PAH
      metabolites levels found were in the same range or lower than those reported from
      other European countries and they were higher than those found in the U.S. This
      study represents the first nationwide survey of exposure to PAHs in Spain and
      provides a background reference range for exposure to PAHs in the Spanish adult
      occupied population.

PMID- 25600324
TI  - Protein aggregation in Alzheimer's disease: Abeta and tau and their potential
      roles in the pathogenesis of AD.

PMID- 25600325
TI  - Growth of high-density horizontally aligned SWNT arrays using Trojan catalysts.
AB  - Single-walled carbon nanotube (SWNT)-based electronics have been regarded as one
      of the most promising candidate technologies to replace or supplement silicon
      based electronics in the future. These applications require high-density
      horizontally aligned SWNT arrays. During the past decade, significant efforts
      have been directed towards growth of high-density SWNT arrays. However, obtaining
      SWNT arrays with suitable density and quality still remains a big challenge.
      Herein, we develop a rational approach to grow SWNT arrays with ultra-high
      density using Trojan catalysts. The density can be as high as 130 SWNTs MUm(-1).
      Field-effect transistors fabricated with our SWNT arrays exhibit a record drive
      current density of -467.09 MUA MUm(-1) and an on-conductance of 233.55 MUS MUm(
      1). Radio frequency transistors fabricated on these samples exhibit high
      intrinsic fT and fMAX of 6.94 and 14.01 GHz, respectively. These results confirm
      our high-density SWNT arrays are strong candidates for applications in
      electronics. 

PMID- 25600326
TI  - Women's experiences of coping with pain during childbirth: a critical review of
      qualitative research.
AB  - OBJECTIVE: to identify and analyse qualitative literature exploring women's
      experiences of coping with pain during childbirth. DESIGN: critical review of
      qualitative research. FINDINGS: ten studies were included, conducted in
      Australia, England, Finland, Iceland, Indonesia, Iran and Sweden. Eight of the
      studies employed a phenomenological perspective with the remaining two without a
      specific qualitative methodological perspective. Thematic analysis was used as
      the approach for synthesising the data in this review. Two main themes emerged as
      the most significant influences upon a woman's ability to cope with pain: (i) the
      importance of individualised, continuous support and (ii) an acceptance of pain
      during childbirth. This review found that women felt vulnerable during childbirth
      and valued the relationships they had with health professionals. Many of the
      women perceived childbirth pain as challenging, however, they described the
      inherent paradox for the need for pain to birth their child. This allowed them to
      embrace the pain subsequently enhancing their coping ability. KEY CONCLUSIONS:
      women's experience of coping with pain during childbirth is complex and
      multifaceted. Many women felt the need for effective support throughout
      childbirth and described the potential implications where this support failed to
      be provided. Feeling safe through the concept of continuous support was a key
      element of care to enhance the coping ability and avoid feelings of loneliness
      and fear. A positive outlook and acceptance of pain was acknowledged by many of
      the women, demonstrating the beneficial implications for coping ability. These
      findings were consistent despite the socio-economic, cultural and contextual
      differences observed within the studies suggesting that experiences of coping
      with pain during childbirth are universal. IMPLICATIONS FOR PRACTICE: the
      findings suggest there is a dissonance between what women want in order to
      enhance their ability to cope with pain and the reality of clinical practice.
      This review found women would like health professionals to maintain a continuous
      presence throughout childbirth and support a social model of care that promotes
      continuity of care and an increasing acceptance of pain as part of normal
      childbirth. It is suggested future research regarding the role of antenatal
      provision for instilling such a viewpoint in preparation of birth be undertaken
      to inform policy makers. The need for a shift in societal norms is also suggested
      to disseminate expectations and positive or negative views of what the role of
      pain during childbirth should be to empower women to cope with childbirth and
      embrace this transition to motherhood as part of a normal process.

PMID- 25600327
TI  - An explorative study of factors contributing to the job satisfaction of primary
      care midwives.
AB  - OBJECTIVE: the main objectives of our study was to gain an understanding of how
      primary care midwives in the Netherlands feel about their work and to identify
      factors associated with primary care midwives' job satisfaction and areas for
      improvement. DESIGN: a qualitative analysis was used, based on the
      constructivist/interpretative paradigm. Three open-ended questions in written or
      online questionnaire, analysed to identify factors that are linked with job
      satisfaction, were as follows: 'What are you very satisfied with, in your work as
      a midwife?', 'What would you most like to change about your work as a midwife?'
      and 'What could be improved in your work?'. SETTING: 20 of the 519 primary care
      practices in the Netherlands in May 2010 were included. PARTICIPANTS: at these
      participating practices 99 of 108 midwives returned a written or online
      questionnaire. FINDINGS: in general, most of the participating primary care
      midwives were satisfied with their job. The factors positively associated with
      their job satisfaction were their direct contact with clients, the supportive co
      operation and teamwork with immediate colleagues, the organisation of and
      innovation within their practice group and the independence, autonomy, freedom,
      variety and opportunities that they experienced in their work. Regarding
      improvements, the midwives desired a reduction in non-client-related activities,
      such as paperwork and meetings. They wanted a lower level of work pressure, and a
      reduced case-load in order to have more time to devote to individual clients'
      needs. Participants identified that co-operation with other partners in the
      health care system could also be improved. KEY CONCLUSIONS: our knowledge, our
      study is the first explorative study on factors associated with job satisfaction
      of primary care midwives. While there are several studies on job satisfaction in
      health care; little is known about the working conditions of midwives in primary
      care settings. Although the participating primary care midwives in the
      Netherlands were satisfied with their job, areas for improvement were identified.
      The results of our study can be relevant for countries that have a comparable
      obstetric system as in the Netherlands, or are implementing or scaling up
      midwifery-led care.

PMID- 25600328
TI  - [Carbapenemase-producing enterobacteriae: epidemiology, strategies to control
      their spread and issues].
AB  - The increasing bacterial resistance to antibiotics has become a major public
      health concern bringing the threat of therapeutic impasses. In this context,
      control of the spread of highly-resistant bacteria emerging antibiotics (BHRe),
      such as glycopeptide-resistant enterococci (VRE) and Enterobacteriaceae producing
      carbapenemases (CPE), is based on a dual strategy of reducing the prescription of
      antibiotics to limit the pressure selection and preventing the spread from
      carriers. Prevention strategy is based on three different levels such as standard
      precautions for all patients with a particular focus on the management of
      excreta, and additional precautions for BHRe carriers. What makes it difficult is
      that carriage is usually completely asymptomatic, enterobacteria and enterococci
      are normal commensal of gut microbiota. Explosive dissemination of
      Enterobacteriaceae producing extended spectrum beta-lactamases in hospital and
      community heralds the emergence of CPE whose import by patients with a history of
      hospitalization in abroad may be the main source of spread in France. 

PMID- 25600329
TI  - [Idiopathic and secondary capillary leak syndromes: A systematic review of the
      literature].
AB  - PURPOSE: The capillary leak syndrome (CLS) is a rare condition characterized by
      the onset of hypotension, edema, hemoconcentration and hypoalbuminemia. CLS can
      be idiopathic (Clarkson's disease) or secondary to various conditions and
      treatments. Here, we review the clinical and biological features,
      pathophysiology, causes and treatment of this rare condition. METHODS: We
      performed a systematic review of the literature (Medline database through
      February 2014) to identify all articles about CLS. The relevant references were
      selected by two independent authors. RESULTS: Secondary CLSs are mostly due to
      malignant hematological diseases, viral infections, and treatments such as
      chemotherapies and therapeutic growth factors. Diagnosis of idiopathic CLS is
      made by exclusion of secondary diseases, especially as a serum monoclonal
      immunoglobulin is present, or when there is a relapsing disease, no initial lung
      involvement or preserved consciousness despite low blood pressure. Acute episodes
      are treated with vasopressor therapy and judicious fluid replacement. Between
      episodes, patients with Clarkson's disease may be treated with intravenous
      immunoglobulins. CLS is a severe disease with significantly impaired prognosis.
      CONCLUSION: Clarification of the pathophysiological mechanisms of CLS is
      essential to improve the prognosis of this rare disease with more targeted
      treatments.

PMID- 25600331
TI  - The effects of display size on performance.
AB  - We examined the systematic effects of display size on task performance as derived
      from a standard perceptual and cognitive test battery. Specifically, three
      experiments examined the influence of varying viewing conditions on response
      speed, response accuracy and subjective workload at four differing screen sizes
      under three different levels of time pressure. Results indicated a ubiquitous
      effect for time pressure on all facets of response while display size effects
      were contingent upon the nature of the viewing condition. Thus, performance
      decrement and workload elevation were evident only with the smallest display size
      under the two most restrictive levels of time pressure. This outcome generates a
      lower boundary threshold for display screen size for this order of task demand.
      Extrapolations to the design and implementation of all display sizes and forms of
      cognitive and psychomotor demand are considered. 

PMID- 25600334
TI  - A technical tip for total laparoscopic type II endoleak repair.
AB  - Laparoscopy is a minimally invasive alternative for type II endoleak repair after
      endovascular aneurysm repair. However, control of lumbar and median sacral
      arteries is considered technically difficult due to the dense inflammatory tissue
      surrounding the aorta. We describe a technical tip that avoids close dissection
      of the aneurysm sac. After the transperitoneal approaches we commonly use during
      laparoscopic aortic surgery, the aneurysm is drawn rightward to access the plane
      of the anterior longitudinal ligament. This technique allows a direct exposure of
      the lumbar and median sacral arteries, which are all methodically dissected and
      ligated along the anterior wall of the spine without close dissection of the
      aneurysm sac. In our experience, this technical tip was always feasible and
      simplified laparoscopic type II endoleak repair. 

PMID- 25600332
TI  - Automatically Recognizing Medication and Adverse Event Information From Food and
      Drug Administration's Adverse Event Reporting System Narratives.
AB  - BACKGROUND: The Food and Drug Administration's (FDA) Adverse Event Reporting
      System (FAERS) is a repository of spontaneously-reported adverse drug events
      (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured
      reports and unstructured narratives. The narratives often include essential
      information for evaluation of the severity, causality, and description of ADEs
      that are not present in the structured data. The timely identification of unknown
      toxicities of prescription drugs is an important, unsolved problem. OBJECTIVE:
      The objective of this study was to develop an annotated corpus of FAERS
      narratives and biomedical named entity tagger to automatically identify ADE
      related information in the FAERS narratives. METHODS: We developed an annotation
      guideline and annotate medication information and adverse event related entities
      on 122 FAERS narratives comprising approximately 23,000 word tokens. A named
      entity tagger using supervised machine learning approaches was built for
      detecting medication information and adverse event entities using various
      categories of features. RESULTS: The annotated corpus had an agreement of over .9
      Cohen's kappa for medication and adverse event entities. The best performing
      tagger achieves an overall performance of 0.73 F1 score for detection of
      medication, adverse event and other named entities. CONCLUSIONS: In this study,
      we developed an annotated corpus of FAERS narratives and machine learning based
      models for automatically extracting medication and adverse event information from
      the FAERS narratives. Our study is an important step towards enriching the FAERS
      data for postmarketing pharmacovigilance.

PMID- 25600333
TI  - Experience matters more than specialty for carotid stenting outcomes.
AB  - OBJECTIVE: The introduction of carotid stenting has led to a rapid rise in the
      number of vascular specialists performing this procedure. The Carotid
      Revascularization Endarterectomy vs Stenting Trial (CREST) has shown that carotid
      stenting can be performed with an equivalent major event rate compared with
      carotid endarterectomy. However, there is still controversy about the appropriate
      training and experience required to safely perform this procedure. This
      observational study examined the performance of carotid stenting with regard to
      specialty and case volume. METHODS: From 2004 to 2011, inpatients diagnosed with
      carotid stenosis who had a carotid stenting procedure were extracted from the
      Nationwide Inpatient Sample database. The cohort was separated on the basis of
      the provider performing the procedure (surgeon vs interventionalist), hospital
      location, and volume. Surgeons were defined as providers who also performed
      either a carotid endarterectomy or femoral-popliteal bypass during the same time
      interval. Primary end points analyzed included stroke, myocardial infarction, and
      30-day mortality. Length of stay and hospital costs were also analyzed as
      secondary outcomes. RESULTS: A total of 20,663 cases of carotid stenting were
      found; 15,305 (74%) cases were identified to be performed by a "surgeon," whereas
      5358 (26%) were done by an "interventionalist." The majority of cases were done
      at hospitals in urban locations (96.51%) and designated teaching institutions
      (61.47%). Unadjusted outcomes were similar between surgeons and
      interventionalists in terms of stroke (4.33% and 4.41%), myocardial infarction
      (2.10% and 2.13%), and mortality (0.84% and 1.03%) respectively. Qualitatively,
      volume per 10 cases was shown to decrease the risk of stroke. Adjusted
      multivariate analysis demonstrated no statistical significance between primary
      end point outcomes. However, length of stay (2.81 vs 3.08 days) and total charges
      ($48,087.61 and $51,718.77) were lower for procedures performed by surgeons.
      CONCLUSIONS: Surgeons are performing the majority of carotid stent procedures in
      the United States. The volume of cases performed by a provider, rather than the
      provider's specialty, appears to be a stronger predictor of adverse outcomes for
      carotid stenting. There were, however, significant cost differences between
      surgeons and interventionalists, which needs to be further evaluated at an
      institutional level.

PMID- 25600335
TI  - Type Ia endoleaks after fenestrated and branched endografts may lead to component
      instability and increased aortic mortality.
AB  - OBJECTIVES: Fenestrated and branched endografts allow for proximal sealing zone
      extension into or above the visceral aorta to optimize landing in healthy aorta.
      We describe the incidence, causes, and implications of proximal endoleak
      development in patients undergoing complex endovascular aortic aneurysm repair.
      METHODS: All patients undergoing a fenestrated/branched repair were entered onto
      a prospective database, and this analysis included all those with at least one
      postoperative contrast computed tomography scan. Preoperative and postoperative
      three-dimensional imaging was reanalyzed to characterize morphology and identify
      endoleak. A blinded assessor used the preoperative imaging to resize the repairs
      in the endoleak group and a matched cohort of patients without endoleak. The
      outcome measures were proximal endoleak development, mortality, and component
      stability, and a comparison was made with all patients undergoing complex aortic
      repair. RESULTS: From 2001 to July 2013, 969 patients underwent repair in a
      physician-sponsored investigational device exemption trial. Excluded were 24
      emergency patients and 21 patients without requisite imaging, leaving 924
      available for analysis. A proximal type Ia endoleak developed in 26 patients
      (2.8%). Poor choice of landing zone was implicated in most cases, with an area of
      sealing in the visceral aorta, compared with the thoracic aorta, being
      significantly associated with endoleak development (P < .01). Aortic-related
      mortality was significantly higher in the endoleak group (26.9%) than in the
      group without endoleak (6.2%; P = .001). These patients also experienced a higher
      incidence of component instability of 30.8% compared with 9.6% in patients
      without type Ia endoleak (P < .01). CONCLUSIONS: Fenestrated/branched
      endovascular repair has a low incidence of sealing zone failure despite the
      increased complexity. However, development of a proximal endoleak destabilizes
      the repair and leads to increased mortality. Increasing complexity of design
      seems to improve the long-term outcome for patients requiring complex aortic
      repair.

PMID- 25600336
TI  - Technique of supraclavicular decompression for neurogenic thoracic outlet
      syndrome.
AB  - The supraclavicular approach to scalenectomy and first rib resection has been
      modified since the original description in 1985. The incision is 1 to 2 cm above
      the clavicle, 1 cm lateral to the midline, and 5 to 7 cm long. Subplatysmal skin
      flaps are created. The sternocleidomastoid muscle is mobilized on its lateral
      edge and retracted but not divided. The scalene fat pad is split vertically, the
      omohyoid muscle excised, and the C5 nerve root dissected free. The accessory
      phrenic nerve is identified, if present, arising medially from C5, and preserved.
      The rest of the plexus is dissected free, muscular and connective tissue removed
      from all nerve roots and trunks, and the subclavian artery identified. The
      phrenic nerve is identified on the medial edge of the anterior scalene muscle
      (ASM). The ASM is divided on the first rib. The ASM is elevated, freed, and
      divided as high as possible and free of C5. The middle scalene muscle is
      dissected. C5 and C6 branches of the long thoracic nerve are identified and
      protected as the portion of middle scalene muscle adjacent to the nerves of the
      plexus is excised. The decision on whether the first rib is to be removed is
      determined by whether the lower trunk of the plexus is touching the first rib. If
      the rib is removed, its posterior end is freed, divided, and 1 cm excised. The
      rest of the rib is freed from the intercostal muscles with a periosteal elevator
      or harmonic scalpel, the pleura is separated from the inner surface of the rib,
      and the anterior end divided with an infraclavicular rib cutter. The operation
      has been made safer by identifying and dissecting the C5 nerve root before
      looking for the phrenic nerve.

PMID- 25600337
TI  - Technique and outcomes of robot-assisted median arcuate ligament release for
      celiac artery compression syndrome.
AB  - OBJECTIVE: Celiac artery compression by the median arcuate ligament (MAL) is a
      potential cause of postprandial abdominal pain and weight loss that overlaps with
      other common syndromes. Robotic technology may alter the current paradigm for
      surgical intervention. Open MAL release is often performed with concurrent bypass
      for celiac stenosis due to the morbidity of reintervention, whereas the
      laparoscopic approach is associated with high rates of conversion to open due to
      bleeding. We hypothesized that a robot-assisted technique might minimize
      conversion events to open, decrease perioperative morbidity, and defer
      consideration of vascular bypass at the initial operative setting. METHODS: We
      retrospectively analyzed patients treated for MAL syndrome by a multidisciplinary
      team at a tertiary medical center between September 2012 and December 2013.
      Diagnosis was based on symptom profile and peak systolic velocity (PSV) >200 cm/s
      during celiac artery duplex ultrasound imaging. All patients underwent robot
      assisted MAL release with simultaneous circumferential neurolysis of the celiac
      plexus. Postoperative celiac duplex and symptom profiles were reassessed
      longitudinally to monitor outcomes. RESULTS: Nine patients (67% women) were
      evaluated for postprandial pain (100%) and weight loss (100%). All patients had
      celiac stenosis by mesenteric duplex ultrasound imaging (median PSV, 342; range,
      238-637 cm/s), and cross-sectional imaging indicated a fishhook deformity in five
      (56%). Robot-assisted MAL release was completed successfully in all nine patients
      (100%) using a standardized surgical technique. Estimated blood loss was <50 mL,
      with a median hospital stay of 2 days (range, 2-3 days). No postoperative
      complications of grade >=3, readmissions or reoperations were observed. All
      patients (100%) improved symptomatically at the 25-week median follow-up. Three
      patients experienced complete resolution on postoperative celiac duplex
      ultrasound imaging, and six patients showed an improved but persistent stenosis
      (PSV >200 cm/s) compared with preoperative velocities (P < .05 by Wilcoxon signed
      rank). No patients required additional treatment. CONCLUSIONS: Robot-assisted MAL
      release can be performed safely and effectively with avoidance of conversion
      events and minimal morbidity. Potential factors contributing to success are
      patient selection by a multidisciplinary team and replication of the open
      surgical technique by means of robot-assisted dexterity and visualization. The
      need for delayed reintervention for persistently symptomatic celiac stenosis is
      uncertain.

PMID- 25600338
TI  - The osteogenic niche promotes early-stage bone colonization of disseminated
      breast cancer cells.
AB  - Breast cancer bone micrometastases can remain asymptomatic for years before
      progressing into overt lesions. The biology of this process, including the
      microenvironment niche and supporting pathways, is unclear. We find that bone
      micrometastases predominantly reside in a niche that exhibits features of
      osteogenesis. Niche interactions are mediated by heterotypic adherens junctions
      (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the
      disruption of which abolishes niche-conferred advantages. We elucidate that hAJ
      activates the mTOR pathway in cancer cells, which drives the progression from
      single cells to micrometastases. Human data set analyses support the roles of AJ
      and the mTOR pathway in bone colonization. Our study illuminates the initiation
      of bone colonization, and provides potential therapeutic targets to block
      progression toward osteolytic metastases. 

PMID- 25600340
TI  - Characterization of a new human plasma cell leukemia cell line UHKT-944.
AB  - OBJECTIVE: A new interleukin-6 (IL-6)-dependent plasma cell leukemia cell line
      UHKT-944 was established from bone marrow cells derived from a 55-yr-old man with
      plasma cell leukemia. RESULTS: The cell line possesses phenotypic characteristics
      of plasma cells including the production of a monoclonal immunoglobulin IgA1
      kappa. VH3-9 region of IgVH genes was rearranged and somatically hypermutated.
      The UHKT-944 cells were found to be negative for most of tested B-cell, T-cell,
      and myeloid markers. According to cytogenetic analysis, the cells were classified
      as near tetraploid with several numerical and structural abnormalities including
      the t(14;20) involving IgH locus. CONCLUSION: The established permanent plasma
      cell leukemia cell line is a suitable model for the study of cellular and
      molecular mechanisms of pathogenesis of this rare malignant disease.

PMID- 25600339
TI  - Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of
      BRAF/MEK cotargeting but result in melanoma drug addiction.
AB  - Combined BRAF- and MEK-targeted therapy improves upon BRAF inhibitor (BRAFi)
      therapy but is still beset by acquired resistance. We show that melanomas acquire
      resistance to combined BRAF and MEK inhibition by augmenting or combining
      mechanisms of single-agent BRAFi resistance. These double-drug resistance
      associated genetic configurations significantly altered molecular interactions
      underlying MAPK pathway reactivation. (V600E)BRAF, expressed at
      supraphysiological levels because of (V600E)BRAF ultra-amplification, dimerized
      with and activated CRAF. In addition, MEK mutants enhanced interaction with
      overexpressed (V600E)BRAF via a regulatory interface at R662 of (V600E)BRAF.
      Importantly, melanoma cell lines selected for resistance to BRAFi+MEKi, but not
      those to BRAFi alone, displayed robust drug addiction, providing a potentially
      exploitable therapeutic opportunity. 

PMID- 25600342
TI  - Comment on: Retrospective study of human cystic echinococcosis in Italy based on
      the analysis of hospital discharge records between 2001 and 2012.

PMID- 25600341
TI  - [Selection of medical graduates for residency posts. A comparative study of the
      methodologies used in different countries].
AB  - INTRODUCTION: The design of an appropriate method for the selection of medical
      graduates for residency posts is extremely important, not only for the efficiency
      of the method itself (accurate identification of most competent candidates), but
      also for its influence on the study and teaching methodologies operating in
      medical schools. Currently, there is a great variation in the criteria used in
      different countries and there is no definitively appropriate method. The use of
      isolated or combined criteria, such as the marks obtained by students in medical
      schools, their performance in tests of theoretical knowledge and evaluations of
      clinical competence, or personal interviews, have a limited value for identifying
      those candidates who will perform better during the residency and later on during
      independent practice. OBJECTIVES: To analyse the variability in the methodologies
      used for the selection of residents employed in different countries, in
      particular those used in the United Kingdom and USA, where external agencies and
      medical schools make systematic analyses of curriculum development. The
      advantages and disadvantages of national or transnational licensing examinations
      on the process of convergence and harmonization of medical degrees and residency
      programmes through Europe are discussed. The present analysis is used to design a
      new and more efficient multi-criteria methodology for resident selection in
      Spain, which will be published in the next issue of this journal. CONCLUSIONS:
      Since the multi-criteria methods used in UK and USA appear to be most consistent,
      these have been employed for designing the new methodology that could be applied
      in Spain. Although many experts in medical education reject national examinations
      for awarding medical degrees or ranking candidates for residency posts, it seems
      that, when appropriately designed, they can be used to verify the level of
      competence of graduating students without necessarily distorting curriculum
      implementation or improvement.

PMID- 25600343
TI  - Response to comment on: Retrospective study of human cystic echinococcosis in
      Italy based on the analysis of hospital discharge records between 2001 and 2012.

PMID- 25600344
TI  - Double dissociation of error inhibition and correction deficits after basal
      ganglia or dorsomedial frontal damage in humans.
AB  - Effective self-control relies on the rapid adjustment of inappropriate responses.
      Understanding the brain basis of these processes has the potential to inform
      neurobiological models of the many neuropsychiatric disorders that are marked by
      maladaptive responding. Research on error processing in particular has implicated
      the dorsomedial frontal lobe (DMF) and basal ganglia (BG) in error detection,
      inhibition and correction. However there is controversy regarding the specific
      contributions of these regions to each of these component processes. Here we
      examined the effects of lesions affecting DMF or BG on these error-related
      processes. A flanker task was used to induce errors that in turn led to
      spontaneous, online corrections, while response kinematics were measured with
      high spatiotemporal resolution. The acceleration of errors was initially greater
      than that of correct responses. Errors then showed slower acceleration compared
      to correct responses, consistent with engagement of inhibition shortly after
      error response onset. BG damage disproportionately disrupted this early
      inhibitory phenomenon, above and beyond effects on baseline motor performance,
      but did not affect the kinematics of the corrective response. DMF damage showed
      the opposite pattern, with relatively delayed onset and weaker initial
      acceleration of the corrective response, but error suppression kinematics similar
      to that of the control group. This work clarifies the component processes and
      neural substrates of online post-error control, providing evidence for
      dissociable contributions of BG to error inhibition, but not correction, and DMF
      to rapid error correction, but not error suppression. 

PMID- 25600345
TI  - Controversies in arrhythmias and arrhythmic syndromes of active children and
      young adults.
AB  - Important advances in the diagnosis and therapy of various arrhythmic disorders
      have been made in the last two decades. These, in turn, have necessitated a re
      examination of current practice guidelines, with a view to deciding on optimal
      management of young patients with suspected or proven arrhythmia syndromes and in
      assessing the risk of adverse arrhythmic events during sport participation. There
      has also been a concomitant emphasis on identifying individuals at risk by
      nationwide screening programs using the ECG and excluding them from competitive
      sport. This review identifies some of these issues, looks at the data critically
      and offers some suggestions for current care and future research. 

PMID- 25600346
TI  - Improving the diagnostic accuracy for detecting cardiac sarcoidosis.
AB  - Cardiac sarcoid is a potentially fatal condition that presents with a wide range
      of clinical manifestations including conduction abnormalities, tachyarrhythmias,
      congestive heart failure, cardiomyopathy and sudden cardiac death. Small
      observational registries and non-comparative studies have described clinical
      evidence of cardiac involvement in 5% of patients with systemic sarcoid, yet
      autopsy studies suggest prevalence as high as 79%. This suggests that cardiac
      sarcoidosis (CS) is underdiagnosed in everyday clinical practice. The scarcity of
      data and lack of consensus on the most appropriate methods for detecting,
      monitoring and treating CS presents a significant diagnostic and therapeutic
      challenge. This review explores the potential impact of novel strategies,
      including multimodality imaging, on the diagnostic accuracy for detecting CS and
      treatment. 

PMID- 25600348
TI  - Understanding basic muscle electrophysiology while keeping an eye on diseases of
      the heart, lung and blood.

PMID- 25600347
TI  - The development of self-emulsifying oil-in-water emulsion adjuvant and an
      evaluation of the impact of droplet size on performance.
AB  - Microfluidization is an established technique for preparing emulsion adjuvant
      formulations for use in vaccines. Although this technique reproducibly yields
      high-quality stable emulsions, it is complex, expensive, and requires proprietary
      equipment. For this study, we developed a novel and simple low shear process to
      prepare stable reproducible emulsions without the use of any proprietary
      equipment. We found this process can produce a wide range of differently sized
      emulsions based on the modification of ratios of oil and surfactants. Using this
      process, we prepared a novel 20-nm-sized emulsion that was stable, reproducible,
      and showed adjuvant effects. During evaluation of this emulsion, we studied a
      range of emulsions with the same composition all sized below 200; 20, 90, and 160
      nm in vivo and established a correlation between adjuvant size and immune
      responses. Our studies indicate that 160-nm-sized emulsions generate the
      strongest immune responses.

PMID- 25600349
TI  - Risk factors for incidental durotomy during lumbar surgery: a retrospective study
      by multivariate analysis.
AB  - OBJECTIVE: The purpose of the present study was to use a prospectively collected
      data to evaluate the rate of incidental durotomy (ID) during lumbar surgery and
      determine the associated risk factors by using univariate and multivariate
      analysis. METHODS: We retrospectively reviewed 2184 patients who underwent lumbar
      surgery from January 1, 2009 to December 31, 2011 at a single hospital. Patients
      with ID (n=97) were compared with the patients without ID (n=2019). The
      influences of several potential risk factors that might affect the occurrence of
      ID were assessed using univariate and multivariate analyses. RESULTS: The overall
      incidence of ID was 4.62%. Univariate analysis demonstrated that older age,
      diabetes, lumbar central stenosis, posterior approach, revision surgery, prior
      lumber surgery and minimal invasive surgery are risk factors for ID during lumbar
      surgery. However, multivariate analysis identified older age, prior lumber
      surgery, revision surgery, and minimally invasive surgery as independent risk
      factors. CONCLUSION: Older age, prior lumber surgery, revision surgery, and
      minimal invasive surgery were independent risk factors for ID during lumbar
      surgery. These findings may guide clinicians making future surgical decisions
      regarding ID and aid in the patient counseling process to alleviate risks and
      complications.

PMID- 25600350
TI  - Pemphigus herpetiformis: a case series and review of the literature.
AB  - BACKGROUND: Pemphigus herpetiformis (PH) is a rare subtype of pemphigus that
      presents challenges in diagnosis. OBJECTIVE: To review the presentation,
      diagnosis, and management of PH. METHODS: We reviewed the charts of all patients
      diagnosed and treated for PH in an immunobullous referral center between
      September 2007 and June 2013. RESULTS: Eight patients were identified with a
      diagnosis of PH. All presented initially with pruritus. Clinical disease was
      manifest as either urticated erythematous plaques or a vesiculobullous eruption.
      Histological evaluation demonstrated eosinophilic spongiosis in all patients with
      acantholysis in half of cases (n = 4/8). Peripheral eosinophilia was noted in
      three of eight (37.5%) patients. In all cases, direct immunofluorescence showed
      intercellular deposition of immunoglobulin G in the epidermis. All patients
      required high-dose corticosteroid initially. All patients treated with dapsone or
      sulfasalazine (n = 4) achieved at least partial control. Other effective
      treatments included intravenous immunoglobulin (n = 2), azathioprine (n = 2), and
      leflunomide (n = 1). Rituximab was ineffective in two patients. CONCLUSION: The
      clinical and histological features of PH develop over time and with treatment,
      making distinction between pemphigus subtypes challenging and delay in diagnosis
      common. Diagnosis of PH requires a high index of suspicion and is made on
      clinical grounds (urticated erythema) in the context of compatible histology and
      immunofluorescence findings. Treatment may be challenging, although efficacy of
      sulfonamide derivatives appears to offer a therapeutic effect.

PMID- 25600351
TI  - Procidentia in pregnancy: a systematic review and recommendations for practice.
AB  - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) in pregnancy is a rare
      condition with decreasing incidence and improved management and outcome world
      wide recently. Systematic review of the literature for cases of POP in pregnancy
      published since 1990 was carried out to identify common factors in presentation,
      management and outcomes. One case from our own practice was added to the
      analysis. METHODS: An extensive search of the Pubmed/Medline, Scopus and Google
      Scholar databases was performed to identify all cases of POP in pregnancy since
      1990. Published case reports of POP in pregnancy were reviewed and summarized in
      tables to find similarities in history, course, management and outcome of the
      pregnancies. RESULTS: Of the 43 cases and one case series, 41 case studies were
      eligible for analysis. Two types of POP in pregnancy were identified: preexisting
      is less common (14 vs 27 cases), often resolves during pregnancy (5 out of 14)
      and always recurs after delivery (14 out of 14); acute onset of POP in pregnancy
      rarely resolves in pregnancy (2 out of 27), but often resolves after delivery (18
      out of 27). Most patients were managed with bed rest (20 out of 41), pessary (15
      out of 41), manual reduction (6 out of 41) and local treatment (6 out of 41). The
      most common complications reported include preterm labour (14 out of 41),
      cervical ulcerations (9 out of 41), infection (3 out of 41) and obstructed labour
      (4 out of 41). About a half of the women delivered vaginally (22 out of 41),
      caesarean section due to prolapse was required in 15 cases. CONCLUSIONS: Two
      distinct entities were identified based on similarities regarding onset, course
      and outcome of POP in pregnancy. Concise recommendations for practice were
      derived from the analysis of case studies published since 1990.

PMID- 25600352
TI  - Urogynecology digest Presented by Aparna Hegde.

PMID- 25600353
TI  - Medium-term comparison of uterus preservation versus hysterectomy in pelvic organ
      prolapse treatment with ProliftTM mesh.
AB  - INTRODUCTION AND HYPOTHESIS: We conducted a medium-term assessment of clinical
      outcomes and complications after surgical repair of pelvic organ prolapse (POP)
      using ProliftTM mesh, and sought to determine whether concomitant hysterectomy
      clinically influenced the outcome of pelvic reconstruction in patients without a
      prior history of urogenital surgery. METHODS: Patients diagnosed with POP-Q stage
      3/4 uterine prolapse at a tertiary referral urogynecology unit in South Taiwan
      who had undergone POP repair with Prolift mesh from May 2007 to July 2010 were
      identified by chart review. Concomitant hysterectomy was performed in 24 patients
      (hysterectomy group), and uterus-sparing surgery in 78 (uterus-sparing group)
      Preoperative and postoperative subjective assessments of urinary and prolapse
      symptoms, objective POP-Q score, urodynamic examination, and postoperative
      adverse events were compared between the groups. RESULTS: The mean follow-up
      periods were 25.7 months (range 6.2 - 73.1 months) and 31.7 months (range 6.0 -
      78.4 months) in the concomitant hysterectomy and uterus-sparing groups,
      respectively. There were no between-group differences in functional and anatomic
      outcomes after surgery. No statistically significant differences were found in
      postoperative adverse events between the groups. CONCLUSIONS: Pelvic
      reconstruction using Prolift with concomitant hysterectomy and uterus-sparing
      surgery have similar anatomic and functional results at 2.5 years. Therefore, we
      consider uterus-sparing surgery to be an alternative to hysterectomy in uterine
      prolapse repair.

PMID- 25600354
TI  - In situ SEM study of lithium intercalation in individual V2O5 nanowires.
AB  - Progress in rational engineering of Li-ion batteries requires better
      understanding of the electrochemical processes and accompanying transformations
      in the electrode materials on multiple length scales. In spite of recent progress
      in utilizing transmission electron microscopy (TEM) to analyze these materials,
      in situ scanning electron microscopy (SEM) was mostly overlooked as a powerful
      tool that allows probing these phenomena on the nano and mesoscale. Here we
      report on in situ SEM study of lithiation in a V2O5-based single-nanobelt battery
      with ionic liquid electrolyte. Coupled with cyclic voltammetry measurements, in
      situ SEM revealed the peculiarities of subsurface intercalation, formation of a
      solid-electrolyte interface (SEI) and electromigration of liquid. We observed
      that single-crystalline vanadia nanobelts do not undergo large-scale
      amorphization or fracture during electrochemical cycling, but rather transform
      topochemically with only a slight shape distortion. The SEI layer seems to have
      significant influence on the lithium ion diffusion and overall capacity of the
      single-nanobelt battery. 

PMID- 25600355
TI  - Developing sustainable trauma care education in Egypt: sequential trauma
      education program, steps to success.
AB  - INTRODUCTION: As one of the leading causes of death and disability in the world,
      human trauma and injury disproportionately affects individuals in developing
      countries. To meet the need for improved trauma care in Egypt, the Sequential
      Trauma Emergency/Education ProgramS (STEPS) course was created through the
      collaborative effort of U.S. and Egyptian physicians. The objective of course
      development was to create a high-quality, modular, adaptable, and sustainable
      trauma care course that could be readily adopted by a lower- or middle-income
      country. METHODS: We describe the development, transition, and host nation
      sustainability of a trauma care training course between a high-income Western
      nation and a lower-middle-income Middle Eastern/Northern African country,
      including the number of physicians trained and the challenges to program
      development and sustainability. RESULTS: STEPS was developed at the University of
      Maryland, based in part on World Health Organization's Emergency and Trauma Care
      materials, and introduced to the Egyptian Ministry of Health and Population and
      Ain Shams University in May 2006. To date, 639 physicians from multiple
      specialties have taken the 4-day course through the Ministry of Health and
      Population or public/governmental universities. In 2008, the course transitioned
      completely to the leadership of Egyptian academic physicians. Multiple Egyptian
      medical schools and the Egyptian Emergency Medicine Board now require STEPS or
      its equivalent for physicians in training. CONCLUSIONS: Success of this
      collaborative educational program is demonstrated by the numbers of physicians
      trained, the adoption of STEPS by the Egyptian Emergency Medicine Board, and
      program continuance after transitioning to in-country leadership and trainers.

PMID- 25600356
TI  - Predicting academic performance in surgical training.
AB  - INTRODUCTION: During surgical residency, trainees are expected to master all the
      6 competencies specified by the ACGME. Surgical training programs are also
      evaluated, in part, by the residency review committee based on the percentage of
      graduates of the program who successfully complete the qualifying examination and
      the certification examination of the American Board of Surgery in the first
      attempt. Many program directors (PDs) use the American Board of Surgery In
      Training Examination (ABSITE) as an indicator of future performance on the
      qualifying examination. Failure to meet an individual program's standard may
      result in remediation or a delay in promotion to the next level of training.
      Remediation is expensive in terms of not only dollars but also resources, faculty
      time, and potential program disruptions. We embarked on an exploratory study to
      determine if residents who might be at risk for substandard performance on the
      ABSITE could be identified based on the individual resident's behavior and
      motivational characteristics. If such were possible, then PDs would have the
      opportunity to be proactive in developing a curriculum tailored to an individual
      resident, providing a greater opportunity for success in meeting the program's
      standards. METHODS: Overall, 7 surgical training programs agreed to participate
      in this initial study and residents were recruited to voluntarily participate.
      Each participant completed an online assessment that characterizes an
      individual's behavioral style, motivators, and Acumen Index. Residents completed
      the assessment using a code name assigned by each individual PD or their
      designee. Assessments and the residents' 2013 ABSITE scores were forwarded for
      analysis using only the code name, thus insuring anonymity. Residents were
      grouped into those who took the junior examination, senior examination, and
      pass/fail categories. A passing score of >=70% correct was chosen a priori.
      Correlations were performed using logistic regression and data were also entered
      into a neural network (NN) to develop a model that would explain performance
      based on data obtained from the TriMetrix assessments. RESULTS: A total of 117
      residents' TriMetrix and ABSITE scores were available for analysis. They were
      divided into 2 groups of 64 senior residents and 53 junior residents. For each
      group, the pass/fail criteria for the ABSITE were set at 70 and greater as
      passing and 69 and lower as failing. Multiple logistic regression analysis was
      complete for pass/fail vs the TriMetrix assessments. For the senior data group,
      it was found that the parameter Theoretical correlates with pass rate (p < 0.043,
      B = -0.513, exp(B) = 0.599), which means increasing theoretical scores yields a
      decreasing likelihood of passing in the examination. For the junior data, the
      parameter Internal Role Awareness correlated with pass/fail rate (p < 0.004, B =
      0.66, exp(B) = 1.935), which means that an increasing Internal Role Awareness
      score increases the likelihood of a passing score. The NN was able to be trained
      to predict ABSITE performance with surprising accuracy for both junior and senior
      residents. CONCLUSION: Behavioral, motivational, and acumen characteristics can
      be useful to identify residents "at risk" for substandard performance on the
      ABSITE. Armed with this information, PDs have the opportunity to intervene
      proactively to offer these residents a greater chance for success. The NN was
      capable of developing a model that explained performance on the examination for
      both the junior and the senior examinations. Subsequent testing is needed to
      determine if the NN is a good predictive tool for performance on this
      examination.

PMID- 25600357
TI  - Surgeon-level reporting presented by funnel plot is understood by doctors but
      inaccurately interpreted by members of the public.
AB  - INTRODUCTION: Risk-adjusted outcome data for general surgeons practicing in the
      United Kingdom were published for the first time in 2013 with the aim of
      increasing transparency, improving standards, and providing the public with
      information to aid decision making. Most specialties used funnel plots to present
      their data. We assess the ability of members of the public (MoP), medical
      students, nonsurgical doctors (NSD), and surgeons to understand risk-adjusted
      surgical outcome data. MATERIAL AND METHODS: A fictitious outcome dataset was
      created and presented in the form of a funnel plot to 10 participants from each
      of the aforementioned group. Standard explanatory text was provided. Each
      participant was given 5 minutes to review the funnel plot and complete a
      questionnaire. For each question, there was only 1 correct answer. RESULTS:
      Completion rate was 100% (n = 40). No difference existed between NSD and
      surgeons. A significant difference for identification of the "worst performing
      surgeon" was noted between surgeons and MoP (p < 0.01) and between NSD and MoP (p
      < 0.01). Half of medical students and MoP claimed they would use this information
      to aid decision making compared with 80% of doctors. MoP reported the funnel plot
      significantly "more difficult" to interpret than surgeons did (p < 0.01) and NSD
      (p < 0.01). CONCLUSIONS: MoP found these data significantly more "difficult to
      understand" and were less likely to both spot "outliers" and use this data to
      inform decisions than doctors. Surgeons should be aware that outcome data may
      require an alternative method of presentation to be understood by MoP.

PMID- 25600358
TI  - DNase II-dependent DNA digestion is required for DNA sensing by TLR9.
AB  - DNase II digests DNA in endolysosomes. In the absence of DNase II, undigested DNA
      activates cytoplasmic DNA-sensing pathways. Little is known, however, about the
      role of DNase II in endolysosomal DNA sensing by TLR9. Here we show that DNase II
      is required for TLR9. We test two types of TLR9 ligands, CpG-A and CpG-B, and
      show that only CpG-A response is impaired in DNase II-deficient dendritic cells
      (DCs). Enzymatically inactive DNase II mutants cannot rescue CpG-A responses.
      DNase II cleaves CpG-A from 20-mer to 11-12-mer. The 3'11-mer CpG-A fragment
      activates DNase II-deficient DCs. CpG-A shows higher co-localization with LAMP
      2(+) lysosomes than CpG-B and induces DNase II localization in LAMP-2(+)
      lysosomes. Moreover, we demonstrate that DNase II is required for TLR9 activation
      by bacterial genomic DNA. Taken together, these results demonstrate that TLR9
      responds to DNA fragments generated by DNase II. 

PMID- 25600359
TI  - Demodicosis: descriptive classification and status of Rosacea, in response to
      prior classification proposed.

PMID- 25600360
TI  - The Electrocardiogram Is a Poor Diagnostic Tool to Detect Left Ventricular
      Hypertrophy in Children: A Comparison with Echocardiographic Assessment of Left
      Ventricular Mass.
AB  - OBJECTIVE: The electrocardiogram (ECG) is used to detect left ventricular
      hypertrophy (LVH) in children and young adults, and it is considered an important
      screening tool for the most common causes of sudden cardiac arrest in the United
      States. However, the reliability and accuracy of the ECG in the detection of LVH
      are poorly understood. This study's objective was to assess the reliability and
      accuracy of ECG parameters predicting LVH in comparison with echocardiographic
      two-dimensional left ventricular mass (2D-LVM) assessment. DESIGN: Two hundred
      fifty patients met study criteria with complete 2D-LVM measurements, temporally
      matched ECGs and no confounding structural heart defects. The echocardiographic
      diagnosis of LVH was made by 2D-LVM z-score > 2. The electrocardiographic
      diagnosis of LVH was fulfilled if specific Q, R, or S wave voltages exceeded the
      normal limits for the respective age groups established by the Davignon,
      Macfarlane and Rijnbeek datasets, or fulfilled the LVH criteria set forth by
      adult indices (Sokolow-Lyon, Cornell, Gubner, Romhilt-Estes). RESULTS: None of
      the ECG parameters showed significant correlation with 2D-LVM z-scores. In the
      detection of LVH, the most commonly used R in V6 voltages showed the following
      results: sensitivity 13-29%, specificity 77-96%, positive predictive value (PPV)
      29-50%, and negative predictive value (NPV) 77%. The overall accuracy ranged 65
      75%. The accuracy of adult indices for LVH ranged from 49% to 78%. CONCLUSIONS:
      The ECG's prediction of LVH is unreliable with dismal sensitivity, variable
      specificity, poor PPV, and barely acceptable NPV. With such overall poor
      reliability, the use of current ECG standards in screening for LVH warrants
      reassessment.

PMID- 25600361
TI  - Antisaccades and executive dysfunction in early drug-naive Parkinson's disease:
      The discovery study.
AB  - BACKGROUND: Cognitive impairment is well recognized in Parkinson's disease (PD),
      but when it begins to develop is unclear. The aim of this study was to identify
      early signs of cognitive impairment along with abnormalities in saccadic behavior
      in newly diagnosed unmedicated PD patients. METHODS: Nineteen drug-naive PD
      patients and 20 controls were examined using a battery of tests, including an
      antisaccade task, phonemic and semantic verbal fluencies, and a switching and
      rule finding task. RESULTS: With simple tasks, no differences were found between
      the two groups. However, cognitive performance of the two groups diverged with
      more complex tasks, occurring independently of PD-related motor impairment.
      Patients exhibited higher antisaccadic error rates and switch costs in the task
      switching test, and performed significantly worse in the rule finding task.
      CONCLUSIONS: Certain cognitive domains and saccadic parameters are already
      significantly impoverished in newly diagnosed Parkinson's patients, even before
      the initiation of medication.

PMID- 25600362
TI  - Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) production by a moderate halophile
      Yangia sp. ND199 using glycerol as a carbon source.
AB  - Yangia sp. ND199, a moderate halophile isolated from mangrove soil sample in
      Vietnam, was found to accumulate poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
      (PHBV) from unrelated carbon sources in a medium with 4.5% (w/v) NaCl.
      Cultivation with glycerol as carbon source and yeast extract as nitrogen source
      resulted in maximum cell dry weight of 5.7 g/l and PHBV content of 52.8 wt%
      (containing 2.9 mol% of 3HV) after 40 h. The 3HV content of the PHBV was the
      highest during initial stages of copolymer production and decreased with increase
      in the copolymer amount with time, but was not affected by changing the pH of the
      culture medium. Only homopolymer poly(3-hydroxybutyrate) was synthesized when
      monosodium glutamate was used as the nitrogen source. Fed-batch cultivation of
      Yangia sp. ND199 with glycerol and yeast extract gave PHBV content and
      productivity of 53.2 wt% and 0.44 g/l/h, respectively, which were reduced to 40.6
      wt% and 0.25 g/l/h, respectively, with crude glycerol as carbon source. Both the
      copolymer content and productivity were improved to 56 wt% and 0.61 g/l/h,
      respectively, by using 1:1 mixture of crude glycerol and high fructose corn
      syrup. This is the first report of PHBV production by a wild-type halophilic
      bacterium using glycerol as carbon source.

PMID- 25600363
TI  - Sex Differences in Spiritual Coping, Forgiveness, and Gratitude Before and After
      a Basic Alcohol Addiction Treatment Program.
AB  - The aim of the study was to examine the sex differences in the initial level of
      spiritual coping, forgiveness, and gratitude and changes occurring in these areas
      during a basic alcohol addiction treatment program. The study involved 112
      persons, including 56 women and 56 men, who started and completed a basic alcohol
      addiction treatment program at day care units of 11 treatment centers. Two
      measurements were taken: one in the first week of the treatment, and one in the
      last week (5th-7th week after baseline). The Spiritual Coping Questionnaire, the
      Forgiveness Scale, and Gratitude Questionnaire were used. When starting the
      therapy, women had a higher level of negative spiritual coping (p = .024) and a
      lower level of forgiveness of others (p = .041) than men. During the therapy,
      positive changes in spiritual coping occurred in both sex groups, although in the
      case of women they involved improvements in more domains and they were stronger.
      The increase in the level of moral values (except for self-forgiveness) was noted
      solely in women. The study reveals the need to take sex differences into
      consideration when introducing spiritual elements into the therapy. 

PMID- 25600364
TI  - Number of teeth and 5-year mortality in an elderly population.
AB  - OBJECTIVES: Several epidemiological studies have shown the association between
      tooth loss and mortality. However, the impact of number of teeth on mortality has
      not yet been fully addressed in an elderly population with many teeth. Thus, the
      purpose of this cohort study was to assess the possible role of number of teeth
      as a predictor of mortality in the elderly. METHODS: The subjects included in
      this study were generated from a cohort study started in 1998. Oral examinations
      and the completion of a questionnaire were carried out. A total of 600 subjects
      aged 70 years were enrolled at baseline. All the subjects were in good general
      health and did not require any special care for their daily activities. The 5
      year mortality data were collected after the baseline survey. After excluding
      those with incomplete data, 569 subjects were analyzed. The Kaplan-Meier method
      was used to analyze survival curves and a Cox regression model to clarify the
      impact of the number of remaining teeth on the 5-year mortality. RESULTS: During
      the follow-up period, 25 (4.4%) subjects died. Subjects with 20 teeth or more had
      a significantly lower mortality rate (2.5%) than those with 19 teeth or fewer
      (6.1%, log-rank test, P = 0.036). Even after adjusting for confounders including
      gender, BMI, serum albumin level, current smoking status, education, number of
      family members living together and a history of chronic diseases, the risk of all
      cause mortality was significantly associated with the number of remaining teeth
      (P = 0.047) with a hazard ratio of 0.96, indicating that there was a 4% point
      increase in the 5-year survival rate per additional tooth retained at the age of
      70. CONCLUSION: The findings of this study suggest that retaining more teeth
      might be a useful indicator for longevity of older people.

PMID- 25600365
TI  - The legacy of the benzodiazepine receptor: from flumazenil to enhancing cognition
      in Down syndrome and social interaction in autism.
AB  - The study of the psychopharmacology of benzodiazepines continues to provide new
      insights into diverse brain functions related to vigilance, anxiety, mood,
      epileptiform activity, schizophrenia, cognitive performance, and autism-related
      social behavior. In this endeavor, the discovery of the benzodiazepine receptor
      was a key event, as it supplied the primary benzodiazepine drug-target site,
      provided the molecular link to the allosteric modulation of GABAA receptors and,
      following the recognition of GABAA receptor subtypes, furnished the platform for
      future, more selective drug actions. This review has two parts. In a
      retrospective first part, it acknowledges the contributions to the field made by
      my collaborators over the years, initially at Hoffmann-La Roche in Basle and
      later, in academia, at the University and the ETH of Zurich. In the second part,
      the new frontier of GABA pharmacology, targeting GABAA receptor subtypes, is
      reviewed with special focus on nonsedative anxiolytics, antidepressants,
      analgesics, as well as enhancers of cognition in Down syndrome and attenuators of
      symptoms of autism spectrum disorders. It is encouraging that a clinical trial
      has been initiated with a partial inverse agonist acting on alpha5 GABAA
      receptors in an attempt to alleviate the cognitive deficits in Down syndrome. 

PMID- 25600366
TI  - Behavioral functions of GABAA receptor subtypes--the Zurich experience.
AB  - GABAA receptors are the major inhibitory neurotransmitter receptors in the brain.
      They are heteropentamers that are typically classified according to their alpha
      subunits. By rendering each of the benzodiazepine-sensitive alpha subunits
      (alpha1, alpha2, alpha3, and alpha5) insensitive to modulation by classical
      benzodiazepines by His to Arg point mutations in knock-in mice, we were able to
      identify behavioral functions mediated by different GABAA receptor subtypes,
      which led to the development of novel therapeutic strategies. In this chapter, we
      provide a largely chronological overview on behavioral studies on GABAA receptor
      mutant mice at the Institute of Pharmacology and Toxicology at the University of
      Zurich. 

PMID- 25600367
TI  - Allosteric modulation of GABAA receptors via multiple drug-binding sites.
AB  - GABAA receptors are ligand-gated ion channels composed of five subunits that can
      be opened by GABA and be modulated by multiple pharmacologically and clinically
      important drugs. Over the time, hundreds of compounds from different structural
      classes have been demonstrated to modulate, directly activate, or inhibit GABAA
      receptors, and most of these compounds interact with more than one binding site
      at these receptors. Crystal structures of proteins and receptors homologous to
      GABAA receptors as well as homology modeling studies have provided insights into
      the possible location of ligand interaction sites. Some of these sites have been
      identified by mutagenesis, photolabeling, and docking studies. For most of these
      ligands, however, binding sites are not known. Due to the high flexibility of
      GABAA receptors and the existence of multiple drug-binding sites, the unequivocal
      identification of interaction sites for individual drugs is extremely difficult.
      The existence of multiple GABAA receptor subtypes with distinct subunit
      composition, the contribution of distinct subunit sequences to binding sites of
      different receptor subtypes, as well as the observation that even subunits not
      directly contributing to a binding site are able to influence affinity and
      efficacy of drugs, contribute to a unique pharmacology of each GABAA receptor
      subtype. Thus, each receptor subtype has to be investigated to identify a
      possible subtype selectivity of a compound. Although multiple binding sites make
      GABAA receptor pharmacology even more complicated, the exploitation of ligand
      interaction with novel-binding sites also offers additional possibilities for a
      subtype-selective modulation of GABAA receptors. 

PMID- 25600370
TI  - Inhibitory neurosteroids and the GABAA receptor.
AB  - gamma-Aminobutyric acid type A receptors (GABAARs) are vital proteins that are
      engaged in regulating neural circuit activity in the central nervous system.
      Their effectiveness in this task is dependent on the extent of receptor
      modulation by naturally occurring ligands that are released in the brain. One of
      the foremost examples of such ligands is the neurosteroids that can either
      potentiate GABAAR function or cause direct inhibition. To fully understand the
      underlying mechanisms by which neurosteroids modulate GABAARs, it is necessary to
      identify their binding sites on the receptors. For potentiating neurosteroids,
      recent work has made substantive progress in identifying a binding site located
      in the transmembrane domains of GABAAR alpha subunits. However, for the
      inhibitory neurosteroids, several possibilities exist including an ion channel
      site as well as potential sites in the transmembrane domain. This review
      systematically analyzes the evidence behind possible binding sites for the
      inhibitory neurosteroids. We consider the chemical structure-function properties
      of such inhibitory neurosteroids, their physiological effects on synaptic
      inhibition, and whether a binding site exists in the GABA ion channel or in other
      areas of the transmembrane domain. Finally, we discuss how structural homology
      modeling and Cys-loop receptor homologues may help to locate the inhibitory
      neurosteroid-binding site on GABAARs. 

PMID- 25600371
TI  - Interactions of flavonoids with ionotropic GABA receptors.
AB  - In this overview, we highlight some recent advances in the interaction of natural
      and synthetic flavonoids with ionotropic GABA receptors. Examples of positive,
      negative, and neutralizing allosteric modulators as well as allosteric agonists
      are given. Flavonoids appear to act via multiple binding sites on GABA receptors.
      Unraveling these active sites remains a major task. 

PMID- 25600372
TI  - GABAA receptor partial agonists and antagonists: structure, binding mode, and
      pharmacology.
AB  - A high degree of structural heterogeneity of the GABAA receptors (GABAARs) has
      been revealed and is reflected in multiple receptor subtypes. The subunit
      composition of GABAAR subtypes is believed to determine their localization
      relative to the synapses and adapt their functional properties to the local
      temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific
      GABAAR antagonists are essential tools for physiological and pharmacological
      elucidation of the different type of GABAAR inhibition. However, distinct
      selectivity among the receptor subtypes (populations) has been shown for only a
      few orthosteric ligands. Still, these examples show that it is indeed possible to
      obtain orthosteric subtype selectivity and they serve as models for further
      development in the orthosteric GABAAR ligand area. This review presents the very
      few existing structural classes of orthosteric GABAAR antagonists and describes
      the development of potent antagonists from partial agonists originally derived
      from the potent GABAAR agonist muscimol. In this process, several heterocyclic
      aromatic systems have been used in combination with structural models in order to
      map the orthosteric binding site and to reveal structural details to be used for
      obtaining potency and subtype selectivity. The challenges connected to functional
      characterization of orthosteric GABAAR partial agonists and antagonists,
      especially with regard to GABAAR stoichiometry and alternative binding sites are
      discussed. GABAAR antagonists have been essential in defining the tonic current
      but both remaining issues concerning the GABAARs involved and the therapeutic
      possibilities of modulating tonic inhibition underline the need for GABAAR
      antagonists with improved selectivity. 

PMID- 25600373
TI  - Closing the gap between the molecular and systemic actions of anesthetic agents.
AB  - Genetic approaches have been successfully used to relate the diverse molecular
      actions of anesthetic agents to their amnestic, sedative, hypnotic, and
      immobilizing properties. The hypnotic effect of etomidate, quantified as the
      duration of the loss of righting reflex in mice, is equally mediated by GABAA
      receptors containing beta2- and beta3-protein subunits. However, only beta3
      containing receptors are involved in producing electroencephalogram (EEG)
      patterns typical of general anesthesia. The sedative action of diazepam is
      produced by alpha1-subunit-containing receptors, but these receptors do not
      contribute to the drug's characteristic EEG-"fingerprint." Thus, GABAA receptors
      with alpha1- and beta2-subunits take a central role in causing benzodiazepine
      induced sedation and etomidate-induced hypnosis, but the corresponding EEG
      signature is difficult to resolve. Contrastingly, actions of etomidate and
      benzodiazepines mediated via alpha2- and beta3-subunits modify rhythmic brain
      activity in vitro and in vivo at least in part by enhancing neuronal synchrony.
      The immobilizing action of GABAergic anesthetics predominantly involves beta3
      subunit-containing GABAA receptors in the spinal cord. Interestingly, this action
      is self-limiting as GABA-release is attenuated via the same receptors. Anesthetic
      induced amnesia is in part mediated by GABAA receptors harboring alpha5-subunits
      that are highly enriched in the hippocampus and, in addition, by alpha1
      containing receptors in the forebrain. Because there is accumulating evidence
      that in patients the expression pattern of GABAA receptor subtypes varies with
      age, is altered by the long-term use of drugs, and is affected by pathological
      conditions like inflammation and sepsis, further research is recommended to adapt
      the use of anesthetic agents to the specific requirements of individual patients.

PMID- 25600369
TI  - Endozepines.
AB  - Since their introduction in the 1960s, benzodiazepines (BZs) remain one of the
      most commonly prescribed medications, acting as potent sedatives, hypnotics,
      anxiolytics, anticonvulsants, and muscle relaxants. The primary neural action of
      BZs and related compounds is augmentation of inhibitory transmission, which
      occurs through allosteric modulation of the gamma-aminobutyric acid (GABA)
      induced current at the gamma-aminobutyric acid receptor (GABAAR). The discovery
      of the BZ-binding site on GABAARs encouraged many to speculate that the brain
      produces its own endogenous ligands to this site (Costa & Guidotti, 1985). The
      romanticized quest for endozepines, endogenous ligands to the BZ-binding site,
      has uncovered a variety of ligands that might fulfill this role, including
      oleamides (Cravatt et al., 1995), nonpeptidic endozepines (Rothstein et al.,
      1992), and the protein diazepam-binding inhibitor (DBI) (Costa & Guidotti, 1985).
      Of these ligands, DBI, and affiliated peptide fragments, is the most extensively
      studied endozepine. The quest for the "brain's Valium" over the decades has been
      elusive as mainly negative allosteric modulatory effects have been observed
      (Alfonso, Le Magueresse, Zuccotti, Khodosevich, & Monyer, 2012; Costa & Guidotti,
      1985), but recent evidence is accumulating that DBI displays regionally discrete
      endogenous positive modulation of GABA transmission through activation of the BZ
      receptor (Christian et al., 2013). Herein, we review the literature on this
      topic, focusing on identification of the endogenous molecule and its region
      specific expression and function. 

PMID- 25600368
TI  - Regulation of GABAARs by phosphorylation.
AB  - gamma-Aminobutyric acid type A receptors (GABAARs) are the principal mediators of
      fast synaptic inhibition in the brain as well as the low persistent extrasynaptic
      inhibition, both of which are fundamental to proper brain function. Thus
      unsurprisingly, deficits in GABAARs are implicated in a number of neurological
      disorders and diseases. The complexity of GABAAR regulation is determined not
      only by the heterogeneity of these receptors but also by its posttranslational
      modifications, the foremost, and best characterized of which is phosphorylation.
      This review will explore the details of this dynamic process, our understanding
      of which has barely scratched the surface. GABAARs are regulated by a number of
      kinases and phosphatases, and its phosphorylation plays an important role in
      governing its trafficking, expression, and interaction partners. Here, we
      summarize the progress in understanding the role phosphorylation plays in the
      regulation of GABAARs. This includes how phosphorylation can affect the
      allosteric modulation of GABAARs, as well as signaling pathways that affect
      GABAAR phosphorylation. Finally, we discuss the dysregulation of GABAAR
      phosphorylation and its implication in disease processes. 

PMID- 25600374
TI  - Preface: a tribute to professor Hanns Mohler.

PMID- 25600375
TI  - Public Awareness of Direct-to-Consumer Genetic Tests: Findings from the 2013 U.S.
      Health Information National Trends Survey.
AB  - Although the availability of direct-to-consumer (DTC) genetic testing has
      increased in recent years, the general public's awareness of this testing is not
      well understood. This study examined levels of public awareness of DTC genetic
      testing, sources of information about testing, and psychosocial factors
      associated with awareness of testing in the USA. Data were obtained from the
      nationally representative 2013 U.S. Health Information National Trends Survey.
      Guided by a social-cognitive conceptual framework, univariable and multivariable
      logistic regressions were conducted to identify factors associated with awareness
      of DTC genetic tests. Of 3185 participants, 35.6% were aware of DTC genetic
      tests, with the majority learning about these tests through radio, television,
      and the Internet. In the final adjusted model, participants with annual incomes
      of $99,999 or less had lower odds of being aware of DTC genetic testing (ORs
      ranging from 0.46-0.61) than did those participants with incomes of $100,000 or
      more. The odds of awareness of DTC genetic tests were significantly higher for
      those who actively seek cancer information (OR=1.91, 95% CI=1.36-2.69), use the
      Internet (OR=1.81, 95% CI=1.05-3.13), and have high numeracy skills (OR=1.67, 95%
      CI=1.17-2.38). It will be critical for healthcare researchers and practitioners
      to understand predictors and consequences of the public's awareness of DTC
      genetic tests, as well as how such awareness may translate into DTC genetic
      testing uptake, health behavior change, and ultimately disease prevention.

PMID- 25600376
TI  - "It All Depends": A Qualitative Study of Parents' Views of Human Papillomavirus
      Vaccine for their Adolescents at Ages 11-12 years.
AB  - Routine vaccination with three doses of human papillomavirus (HPV) vaccine is
      recommended for adolescent girls and boys at 11 or 12 years of age; however,
      vaccine uptake remains suboptimal. To understand the reasons why parents may
      accept or refuse HPV vaccine for their children at age 11 or 12 years, we
      conducted a qualitative study. Semi-structured interviews were conducted with
      parents or guardians (n = 45) whose adolescents receive care at an urban,
      hospital-based primary care practice. Data were analyzed using an iterative
      thematic approach. We found that many parents expressed high levels of support
      for HPV vaccine, including a majority who agreed with vaccination at age 11-12
      years. Parents recognized that for prevention of consequences of HPV infection,
      vaccination of their child early in adolescence was desirable conceptually.
      However, many parents also expressed that in practice, HPV vaccine should be
      given to adolescents at the onset of sexual activity, a perception that led to
      preferences to delay administration of HPV vaccine among certain parents. These
      apparently contradictory views indicate the need for interventions focused on the
      benefits of vaccination at the recommended ages. Our findings may be useful in
      providers' discussions with parents about the vaccine, as pediatric and
      adolescent health care providers have the unique opportunity to educate parents
      and clarify misconceptions about vaccination.

PMID- 25600378
TI  - Support for full disclosure up front.

PMID- 25600377
TI  - Ongoing Controversy over SUPPORT.

PMID- 25600379
TI  - The authors reply.

PMID- 25600380
TI  - Ebola, quarantine, and the law.

PMID- 25600381
TI  - The regulatory gap for preimplantation genetic diagnosis.

PMID- 25600382
TI  - Case study. Faith and futility in the ICU. Commentary.

PMID- 25600383
TI  - Microethics: the ethics of everyday clinical practice.

PMID- 25600384
TI  - Should all research subjects be treated the same?

PMID- 25600385
TI  - SUPPORT: Risks, Harms, and Equipoise.

PMID- 25600386
TI  - The Controversy over SUPPORT Continues and the Hyperbole Increases.

PMID- 25600387
TI  - SUPPORT and Comparative Effectiveness Trials: What's at Stake?

PMID- 25600390
TI  - Safeguarding the Public's Health: Ethical Nursing.

PMID- 25600391
TI  - Is there room for not knowing "everything"?

PMID- 25600392
TI  - Anisotropic quantum confinement effect and electric control of surface states in
      Dirac semimetal nanostructures.
AB  - The recent discovery of Dirac semimetals represents a new achievement in our
      fundamental understanding of topological states of matter. Due to their
      topological surface states, high mobility, and exotic properties associated with
      bulk Dirac points, these new materials have attracted significant attention and
      are believed to hold great promise for fabricating novel topological devices. For
      nanoscale device applications, effects from finite size usually play an important
      role. In this report, we theoretically investigate the electronic properties of
      Dirac semimetal nanostructures. Quantum confinement generally opens a bulk band
      gap at the Dirac points. We find that confinement along different directions
      shows strong anisotropic effects. In particular, the gap due to confinement along
      vertical c-axis shows a periodic modulation, which is absent for confinement
      along horizontal directions. We demonstrate that the topological surface states
      could be controlled by lateral electrostatic gating. It is possible to generate
      Rashba-like spin splitting for the surface states and to shift them relative to
      the confinement-induced bulk gap. These results will not only facilitate our
      fundamental understanding of Dirac semimetal nanostructures, but also provide
      useful guidance for designing all-electrical topological spintronics devices. 

PMID- 25600394
TI  - Carnitine in maintenance hemodialysis patients.
AB  - Carnitine is a conditionally essential metabolite that plays a critical role in
      cell physiology. Carnitine is necessary for fatty acid transport to sites of beta
      oxidation in the mitochondria, where it also helps to prevent organic acid
      accumulation. Because of these key regulatory functions, carnitine represents a
      crucial determinant of mitochondrial energy metabolism, whose deficiency may lead
      to metabolic and clinical disturbances. Loss of carnitine through dialytic
      membranes occurs in maintenance hemodialysis, resulting in potential carnitine
      depletion and relative increments of esterified carnitine forms. Carnitine
      supplementation has been reported to counteract some of these alterations and has
      been associated with some clinical benefits, such as enhanced response to
      erythropoietin as well as improvement in exercise tolerance, intradialytic
      symptom, hyperparathyroidism, insulin resistance, inflammatory and oxidant
      status, protein balance, lipid profile, cardiac function, and quality of life.
      Carnitine supplementation has an attractive theoretical rationale; however, there
      are no definitive supportive studies and conclusive evidence that L-carnitine
      supplementation in maintenance hemodialysis patients could improve these
      conditions. A trial of carnitine administration could be attempted for 6 to 12
      months only in selected patients on dialysis who do not adequately respond to
      standard therapies, in the presence of symptomatology, and in conjunction with
      patient dialysis age and documented L-carnitine deficiency.

PMID- 25600395
TI  - Results for five sets of forensic genetic markers studied in a Greek population
      sample.
AB  - A population sample of 223 Greek individuals was typed for five sets of forensic
      genetic markers with the kits NGM SElectTM, SNPforID 49plex, DIPplex(r), Argus X
      12 and PowerPlex(r) Y23. No significant deviation from Hardy-Weinberg
      expectations was observed for any of the studied markers after Holm-Sidak
      correction. Statistically significant (P<0.05) levels of linkage disequilibrium
      were observed between markers within two of the studied X-chromosome linkage
      groups. AMOVA analyses of the five sets of markers did not show population
      structure when the individuals were grouped according to their geographic origin.
      The Greek population grouped closely to the other European populations measured
      by F(ST)(*) distances. The match probability ranged from a value of 1 in 2*10(7)
      males by using haplotype frequencies of four X-chromosome haplogroups in males to
      1 in 1.73*10(21) individuals for 16 autosomal STRs.

PMID- 25600393
TI  - 25-hydroxyvitamin d and advanced glycation endproducts in healthy and
      hypertensive subjects: are there interactions?
AB  - Advanced glycation endproducts (AGEs) accumulate during aging. Skin is the single
      organ of vitamin D synthesis, induced by ultraviolet B light. Accumulation of
      AGEs in the skin could interfere with synthesis of the vitamin, whereas the
      microinflammation and oxidative stress (associated with hypovitaminosis D) could
      amplify both the toxic effects of AGEs and their production. Clinical data on
      potential interactions between vitamin D3 deficiency and AGE accumulation are
      sparse. Here we investigated potential associations between levels of circulating
      vitamin D3 and those of AGEs in blood and skin with regard to markers of
      inflammation and oxidative stress in nondiabetic subjects. In a cross-sectional
      study, 146 subjects (119 healthy persons and 27 hypertensive patients; 73 male
      and 73 female; mean age, 57.0 +/- 15.5 years) were included. Skin
      autofluorescence (SAF) and plasma levels of vitamin D3, AGE-associated
      fluorescence, high-sensitivity C-reactive protein level, and advanced oxidation
      protein products as well as renal function (estimated glomerular filtration rate)
      were determined. In a subgroup of 61 patients, N(epsilon)-carboxymethyllysine,
      soluble receptor of AGEs, and soluble vascular adhesion protein-1 were
      additionally analyzed. Vitamin D3 level averaged 22.5 +/- 8.9 ng/mL. Prevalence
      of vitamin D insufficiency (20-29 ng/mL) was 43%, and that of deficiency (<20
      ng/mL) 37%. The age-dependent rise in SAF was steeper in smokers and in subjects
      presenting arterial hypertension. No association between SAF and hypovitaminosis
      D was revealed. Among smokers, an inverse relationship manifested between vitamin
      D3 and plasma AGE-associated fluorescence as well as soluble vascular adhesion
      protein-1. Our data suggest that in nondiabetic adults, hypovitaminosis D does
      not enhance toxicity and accumulation of AGEs. Only in smokers interactions are
      conceivable.

PMID- 25600396
TI  - Three step maternal mutation detected by STR analysis.

PMID- 25600398
TI  - Second-sphere coordination-induced morphology transformation from phosphorescent
      nanowires to microcubes.
AB  - Nanowires of a pyridyl-functionalized iridium complex are transformed into
      microcubes as a result of hydrogen-bond-assisted second-sphere coordination
      between pyridyl groups and monovalent anions of 1,3,5-benzenetricarboxylic acid
      (H2BTC(-)). This is accompanied by a blue-shift of the phosphorescence from 662
      to 638 nm. 

PMID- 25600397
TI  - RNA/DNA co-analysis from human skin and contact traces--results of a sixth
      collaborative EDNAP exercise.
AB  - The European DNA profiling group (EDNAP) organized a sixth collaborative exercise
      on RNA/DNA co-analysis for body fluid/tissue identification and STR profiling.
      The task was to identify skin samples/contact traces using specific RNA
      biomarkers and test three housekeeping genes for their suitability as reference
      genes. Eight stains, a skin RNA dilution series and, optionally, bona fide or
      mock casework samples of human or non-human origin were analyzed by 22
      participating laboratories using RNA extraction or RNA/DNA co-extraction methods.
      Two sets of previously described skin-specific markers were used: skin1 pentaplex
      (LCE1C, LCE1D, LCE2D, IL1F7 and CCL27) and skin2 triplex (LOR, KRT9 and CDSN) in
      conjunction with a housekeeping gene, HKG, triplex (B2M, UBC and UCE). The
      laboratories used different chemistries and instrumentation. All laboratories
      were able to successfully isolate and detect mRNA in contact traces (e.g., human
      skin, palm-, hand- and fingerprints, clothing, car interiors, computer
      accessories and electronic devices). The simultaneous extraction of RNA and DNA
      provides an opportunity for positive identification of the tissue source of
      origin by mRNA profiling as well as a simultaneous identification of the body
      fluid donor by STR profiling. The skin markers LCE1C and LOR and the housekeeping
      gene marker B2M were detected in the majority of contact traces. Detection of the
      other markers was inconsistent, possibly due to the low amounts and/or poor
      quality of the genetic material present in shed skin cells. The results of this
      and the previous collaborative RNA exercises support RNA profiling as a reliable
      body fluid/tissue identification method that can easily be combined with current
      STR typing technology.

PMID- 25600399
TI  - Enhancement of chitosan-mediated gene delivery through combination with phiC31
      integrase.
AB  - Gene transfer efficiency and expression stability are key factors to a successful
      gene therapy approach. In the present work we have developed a combined system
      for gene transfer that integrates well established non-viral polymeric vectors
      based on chitosan particles with the properties of phiC31-integrase that promotes
      a relatively non-immunogenic, site-specific integration, with sustained gene
      expression. Simultaneously, to overcome one of the major limitations in adeno
      associated virus mediated gene transfer--the delivery of large genes--we have
      tested the capacity of our non-viral vectors to incorporate a large (8 Kb)
      transgene. Polyplexes were extensively characterized for their size, surface
      charge, morphology, pDNA complexation, transfection efficiency and transgene
      expression in vitro using HEK293 cells. Co-transfection with integrase was done
      by complexation in a single polyplex preparation or the use of two separate
      polyplex preparations. Transgene expression, GFP and CEP290 (1Kb and 8 Kb,
      respectively), was evaluated by fluorescence microscopy, flow cytometry and
      Western blot analysis. DNA complexation efficiency, particle size and morphology
      were consistent with gene delivery for all formulations. In contrast,
      transfection efficiency and transgene expression varied with polymer and polyplex
      size. Following delivery by chitosan polyplexes, high levels of GFP expression
      were still visible 16 weeks post-transfection and over-expression of the large
      transgene was detected at least 6 weeks post-transfection. Polyplexes
      incorporating phiC1 integrase demonstrate prolonged gene expression of both small
      (GFP, 1 Kb) and large genes (CEP290, 8Kb). This approach, using a combined
      strategy of polymers and integrase may overcome the size limitation found in
      commonly used adeno-associated virus mediated gene transfer techniques, while
      maintaining a high safety profile and prolonged, sustained gene expression, thus
      constituting an alternative for gene delivery.

PMID- 25600400
TI  - Fibrin-based 3D matrices induce angiogenic behavior of adipose-derived stem
      cells.
AB  - Engineered three-dimensional biomaterials are known to affect the regenerative
      capacity of stem cells. The extent to which these materials can modify cellular
      activities is still poorly understood, particularly for adipose-derived stem
      cells (ASCs). This study evaluates PEGylated fibrin (P-fibrin) gels as an ASC
      carrying scaffold for encouraging local angiogenesis by comparing with two
      commonly used hydrogels (i.e., collagen and fibrin) in the tissue-engineering
      field. Human ASCs in P-fibrin were compared to cultures in collagen and fibrin
      under basic growth media without any additional soluble factors. ASCs
      proliferated similarly in all gel scaffolds but showed significantly elongated
      morphologies in the P-fibrin gels relative to other gels. P-fibrin elicited
      higher von Willebrand factor expression in ASCs than either collagen or fibrin
      while cells in collagen expressed more smooth muscle alpha actin than in other
      gels. VEGF was secreted more at 7 days in fibrin and P-fibrin than in collagen
      and several other angiogenic and immunomodulatory cytokines were similarly
      enhanced. Fibrin-based matrices appear to activate angiogenic signaling in ASCs
      while P-fibrin matrices are uniquely able to also drive a vessel-like ASC
      phenotype. Collectively, these results suggest that P-fibrin promotes the
      angiogenic potential of ASC-based therapeutic applications.

PMID- 25600401
TI  - Total coliforms, arsenic and cadmium exposure through drinking water in the
      Western Region of Ghana: application of multivariate statistical technique to
      groundwater quality.
AB  - In recent times, surface water resource in the Western Region of Ghana has been
      found to be inadequate in supply and polluted by various anthropogenic
      activities. As a result of these problems, the demand for groundwater by the
      human populations in the peri-urban communities for domestic, municipal and
      irrigation purposes has increased without prior knowledge of its water quality.
      Water samples were collected from 14 public hand-dug wells during the rainy
      season in 2013 and investigated for total coliforms, Escherichia coli, mercury
      (Hg), arsenic (As), cadmium (Cd) and physicochemical parameters. Multivariate
      statistical analysis of the dataset and a linear stoichiometric plot of major
      ions were applied to group the water samples and to identify the main factors and
      sources of contamination. Hierarchal cluster analysis revealed four clusters from
      the hydrochemical variables (R-mode) and three clusters in the case of water
      samples (Q-mode) after z score standardization. Principal component analysis
      after a varimax rotation of the dataset indicated that the four factors extracted
      explained 93.3 % of the total variance, which highlighted salinity, toxic
      elements and hardness pollution as the dominant factors affecting groundwater
      quality. Cation exchange, mineral dissolution and silicate weathering influenced
      groundwater quality. The ranking order of major ions was Na(+) > Ca(2+) > K(+) >
      Mg(2+) and Cl(-) > SO4 (2-) > HCO3 (-). Based on piper plot and the hydrogeology
      of the study area, sodium chloride (86 %), sodium hydrogen carbonate and sodium
      carbonate (14 %) water types were identified. Although E. coli were absent in the
      water samples, 36 % of the wells contained total coliforms (Enterobacter species)
      which exceeded the WHO guidelines limit of zero colony-forming unit (CFU)/100 mL
      of drinking water. With the exception of Hg, the concentration of As and Cd in 79
      and 43 % of the water samples exceeded the WHO guideline limits of 10 and 3 MUg/L
      for drinking water, respectively. Reported values in some areas in Nigeria,
      Malaysia and USA indicated that the maximum concentration of Cd was low and As
      was high in this study. Health risk assessment of Cd, As and Hg based on average
      daily dose, hazard quotient and cancer risk was determined. In conclusion,
      multiple natural processes and anthropogenic activities from non-point sources
      contributed significantly to groundwater salinization, hardness, toxic element
      and microbiological contamination of the study area. The outcome of this study
      can be used as a baseline data to prioritize areas for future sustainable
      development of public wells.

PMID- 25600402
TI  - Veterinary antibiotic resistance, residues, and ecological risks in environmental
      samples obtained from poultry farms, Egypt.
AB  - In Egypt, poultry production constitutes one of the main sources of pollution
      with veterinary antibiotics (VAs) into the environment. About 80 % of meat
      production in Egypt is of poultry origin, and the potential environmental risks
      associated with the use of VAs in these farms have not yet been properly
      evaluated. Thus, the main purpose of this research was to evaluate the prevalence
      of antibiotic-resistant enteric key bacteria and the incidence of residual
      antibiotics in poultry farm environmental samples and to determine whether
      fertilizing soils with poultry litter from farms potentially brings ecological
      risks. From December 2011 to September 2012, a total of 225 litter, bird
      dropping, and water samples were collected from 75 randomly selected boiler
      poultry farms. A high prevalence of Escherichia coli (n = 179; 79.5 %) in
      contrast to the low prevalence of Salmonella spp. (n = 7; 3.1 %) was detected.
      Amongst E. coli isolates, serotypes O142:K86, O125:K70, O91:K, and O119:K69 were
      the most common. Meanwhile, Salmonella enterica serotypes emek and enteritidis
      were recovered. The antibiograms using the disc diffusion method revealed
      significantly more common resistant and multi-resistant isolates in broiler
      poultry farms. Residues of tetracycline and ciprofloxacin were detected at 2.125
      and 1.401 mg kg(-1) mean levels, respectively, in environmental samples
      contaminated with E. coli-resistant strains by HPLC. The risk evaluations
      highlighted that tetracycline residues in poultry litter significantly display
      environmental risks with a hazard quotient value above 1 (1.64). Our study
      implies that ineffective implementation of veterinary laws which guide and guard
      against incorrect VA usage may potentially bring health and environmental risks.

PMID- 25600404
TI  - Sodium and rhodium complexes of a spirocyclic Te5 dianion supported by P2N2
      rings.
AB  - Reactions of the dianion [Te((t)BuN)P(MU-N(t)Bu)2P(N(t)Bu)Te](2-) with I2 or
      [Cp*RhCl2]2 unexpectedly produced complexes of the novel spirocyclic Te5 dianion
      [{(t)BuN(Te)P(MU-N(t)Bu)2P(Te)N(t)Bu}2MU-Te](2-), which is N,N'-coordinated to
      two Na(+) ions in the disodium derivative and adopts a Te,Te',Te''-bonding mode
      in the Cp*Rh complex. 

PMID- 25600403
TI  - Thioredoxin-interacting protein regulates the differentiation of murine erythroid
      precursors.
AB  - Thioredoxin-interacting protein (TXNIP) is involved in various cellular processes
      including redox control, metabolism, differentiation, growth, and apoptosis. With
      respect to hematopoiesis, TXNIP has been shown to play roles in natural killer
      cells, dendritic cells, and hematopoietic stem cells. Our study investigates the
      role of TXNIP in erythropoiesis. We observed a rapid and significant increase of
      TXNIP transcript and protein levels in mouse erythroleukemia cells treated with
      dimethyl sulfoxide or hexamethylene bisacetamide, inducers of erythroid
      differentiation. The upregulation of TXNIP was not abrogated by addition of the
      antioxidant N-acetylcysteine. The increase of TXNIP expression was confirmed in
      another model of erythroid differentiation, G1E-ER cells, which undergo
      differentiation upon activation of the GATA1 transcription factor. In addition,
      we showed that TXNIP levels are induced following inhibition of p38 or c-Jun N
      terminal kinase (JNK) mitogen-activated protein kinases. We also observed an
      increase in iron uptake and a decrease in transferrin receptor protein upon TXNIP
      overexpression, suggesting a role in iron homeostasis. In vivo, flow cytometry
      analysis of cells from Txnip(-/-) mice revealed a new phenotype of impaired
      terminal erythropoiesis in the spleen, characterized by a partial block between
      basophilic and late basophilic/polychromatic erythroblasts. Based on our data,
      TXNIP emerges as a novel regulator of terminal erythroid differentiation. 

PMID- 25600405
TI  - Absolute structures and bioactivities of euryspongins and eurydiene obtained from
      the marine sponge Euryspongia sp. collected at Iriomote Island.
AB  - Three unique sesquiterpenes, named euryspongins A-C (1-3), have been isolated
      from the marine sponge Euryspongia sp. The absolute configuration of 1 was
      assigned as (4R,6R,9S) by comparing its experimental Electronic Circular
      Dichroism (ECD) spectrum with the calculated ECD spectra of both enantiomers, and
      the absolute configurations of 2, 3 and artifact 4 were suggested on the basis of
      that of 1 by assuming common biogenesis of 1-3. These absolute configurations
      were opposite to those depicted in the previous communication. Further separation
      of the remaining fractions lead to the isolation of a new C11-polyketide, named
      as eurydiene (5), together with a known C11-polyketide, nakitriol (6). The
      structure of 5 was assigned on the basis of its spectroscopic data as a bicyclic
      alcohol with a diene side chain. Dehydroeuryspongin A (4) inhibited protein
      tyrosine phosphatase 1B (PTP1B), an important target enzyme for the treatment of
      type II diabetes and obesity, with an IC50 value of 3.58MUM. Moreover, compound 4
      did not inhibit the proliferation of human hepatoma Huh-7 cells at 100MUM. One of
      the locations in which PTP1B has been detected is hepatocytes. Compounds 1-3, 5,
      and 6 were not active against PTP1B. The growth of human colon (HCT-15) and T
      cell lymphoma (Jurkat) cells was not disturbed by compounds 1-6. 

PMID- 25600406
TI  - Design, synthesis and decoration of molecular scaffolds for exploitation in the
      production of alkaloid-like libraries.
AB  - The design, synthesis and decoration of six small molecule libraries is
      described. Each library was inspired by structures embedded in the framework of
      specific alkaloid natural products. The development of optimised syntheses of the
      required molecular scaffolds is described, in which reactions including Pd
      catalysed aminoarylation and diplolar cycloadditions have been exploited as key
      steps. The synthesis of selected exemplar screening compounds is also described.
      In five cases, libraries were subsequently nominated for production on the basis
      of the scope and limitations of the validation work, as well as predicted
      molecular properties. In total, the research has led to the successful synthesis
      of >2500 novel alkaloid-like compounds for addition to the screening collection
      (the Joint European Compound Library, JECL) of the European Lead Factory. 

PMID- 25600407
TI  - Reversible and irreversible small molecule inhibitors of monoamine oxidase B (MAO
      B) investigated by biophysical techniques.
AB  - Monoamine oxidase B (MAO-B) plays a key role in the metabolism of dopamine, a
      neurotransmitter critical for the maintenance of cognitive function.
      Consequently, MAO-B is an important therapeutic target for disorders
      characterized by a decline in dopaminergic neurotransmission, including
      Parkinson's disease (PD). An emerging strategy in drug discovery is to utilize
      the biophysical approaches of thermal shift and isothermal titration calorimetry
      (ITC) to gain insight into binding modality and identify thermodynamically
      privileged chemical scaffolds. Described here is the development of such
      approaches for reversible and irreversible small molecule inhibitors of MAO-B.
      Investigation of soluble recombinant MAO-B revealed mechanism-based differences
      in the thermal shift and binding thermodynamic profiles of MAO-B inhibitors.
      Irreversible inhibitors demonstrated biphasic protein melt curves, large
      enthalpically favorable and entropically unfavorable binding, in contrast to
      reversible compounds, which were characterized by a dose-dependent increase in
      thermal stability and enthalpically-driven binding. The biophysical approaches
      described here aim to facilitate the discovery of next-generation MAO-B
      inhibitors. 

PMID- 25600408
TI  - Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol
      derivatives.
AB  - A series of novel isosteviol derivatives having C4-amide substituents were
      synthesized in order to test for antiviral effects against the hepatitis B virus
      (HBV) in vitro. Among them, IN-4 [N-(propylcarbonyl)-4alpha-amino-19-nor-ent-16
      ketobeyeran] (5) exhibited inhibitory activity against secretion of HBsAg and
      HBeAg as well as inhibition of HBV DNA replication. Therefore, the mechanism of
      its antiviral activity was further analyzed using HBV-transfected Huh7 cells.
      Exposure to IN-4 produced minimal inhibitory effects on viral precore/pregenomic
      RNA expression. However, expression levels of the 2.4/2.1-kb preS/major S RNA of
      the viral surface gene significantly decreased, along with intracellular levels
      of HBV DNA. A promoter activity analysis demonstrated that IN-4 significantly
      inhibited viral X, S, and preS expression levels but not viral core promoter
      activities. In particular, IN-4 was observed to significantly inhibit HBV gene
      regulation by disrupting nuclear factor (NF)-kappaB-associated promoter activity.
      In addition, the nuclear expression of p65/p50 NF-kappaB member proteins was
      attenuated following IN-4 treatment, while cytoplasmic IkappaBalpha protein
      levels were enhanced. Meanwhile, IN-4 was observed to inhibit the binding
      activity of NF-kappaB to putative DNA elements. Furthermore, transfection of a
      p65 expression plasmid into Huh7 cells significantly reversed the inhibitory
      effect of IN-4 on HBV DNA levels, providing further evidence of the central role
      of NF-kappaB in its antiviral mechanism. It is therefore suggested that IN-4
      inhibits HBV by interfering with the NF-kappaB signaling pathway, resulting in
      downregulation of viral gene expression and DNA replication. 

PMID- 25600409
TI  - Cytotoxic acyl amides from the soil fungus Gymnascella dankaliensis.
AB  - The soil fungus Gymnascella dankaliensis was collected in the vicinity of the
      Giza pyramids, Egypt. When grown on solid rice medium the fungus yielded four new
      compounds including 11'-carboxygymnastatin N (1), gymnastatin S (2), dankamide
      (3), and aranorosin-2-methylether (4), the latter having been reported previously
      only as a semisynthetic compound. In addition, six known metabolites (5-10) were
      isolated. Addition of NaCl or KBr to the rice medium resulted in the accumulation
      of chlorinated or brominated compounds as indicated by LC-MS analysis due to the
      characteristic isotope patterns observed. From the rice medium spiked with 3.5%
      NaCl the known chlorinated compounds gymnastatin A (11) and gymnastatin B (12)
      were obtained. All isolated compounds were unambiguously structurally elucidated
      on the basis of comprehensive spectral analysis (1D and 2D NMR, and mass
      spectrometry), as well as by comparison with the literature. Compounds 4, 7 and
      11 showed potent cytotoxicity against the murine lymphoma cell line L5178Y (IC50
      values 0.44, 0.58 and 0.64MUM, respectively), whereas 12 exhibited moderate
      activity with an IC50 value of 5.80MUM. 

PMID- 25600410
TI  - Molecular Evidence for the Polyphyly of Macrotrichomonas (Parabasalia:
      Cristamonadea) and a Proposal for Macrotrichomonoides n. gen.
AB  - Macrotrichomonas (Cristamonadea: Parabasalia) is an anaerobic, amitochondriate
      flagellate symbiont of termite hindguts. It is noteworthy for being large but not
      structurally complex compared with other large parabasalians, and for retaining a
      structure similar in appearance to the undulating membrane (UM) of small
      flagellates closely related to cristamonads, e.g. Tritrichomonas. Here, we have
      characterised the SSU rDNA from two species described as Macrotrichomonas: M.
      restis Kirby 1942 from Neotermes jouteli and M. lighti Connell 1932 from
      Paraneotermes simplicicornis. These species do not form a clade: M. lighti
      branches with previously characterised Macrotrichomonas sequences from
      Glyptotermes, while M. restis branches with the genus Metadevescovina. We
      examined the M. restis UM by light microscopy, scanning electron microscopy, and
      transmission electron microscopy, and we find common characteristics with the
      proximal portion of the robust recurrent flagellum of devescovinids. Altogether,
      we show the genus Macrotrichomonas to be polyphyletic and propose transferring M.
      restis to a new genus, Macrotrichomonoides. We also hypothesise that the
      macrotrichomonad body plan represents the ancestral state of cristamonads, from
      which other major forms evolved.

PMID- 25600411
TI  - Effects of fungal infection on feeding and survival of Anopheles gambiae
      (Diptera: Culicidae) on plant sugars.
AB  - BACKGROUND: The entomopathogenic fungus Metarhizium anisopliae shows great
      promise for the control of adult malaria vectors. A promising strategy for
      infection of mosquitoes is supplying the fungus at plant feeding sites. METHODS:
      We evaluated the survival of fungus-exposed Anopheles gambiae mosquitoes (males
      and females) fed on 6% glucose and on sugars of Ricinus communis (Castor oil
      plant) and Parthenium hysterophorus (Santa Maria feverfew weed). Further, we
      determined the feeding propensity, quantity of sugar ingested and its digestion
      rate in the mosquitoes when fed on R. communis for 12 hours, one and three days
      post-exposure to fungus. The anthrone test was employed to detect the presence of
      sugar in each mosquito from which the quantity consumed and the digestion rates
      were estimated. RESULTS: Fungus-exposed mosquitoes lived for significantly
      shorter periods than uninfected mosquitoes when both were fed on 6% glucose (7
      versus 37 days), R. communis (7 versus 18 days) and P. hysterophorus (5 versus 7
      days). Significantly fewer male and female mosquitoes, one and three days post
      exposure to fungus, fed on R. communis compared to uninfected controls. Although
      the quantity of sugar ingested was similar between the treatment groups, fewer
      fungus-exposed than control mosquitoes ingested small, medium and large meals.
      Digestion rate was significantly slower in females one day after exposure to M.
      anisopliae compared to controls but remained the same in males. No change in
      digestion rate between treatments was observed three days after exposure.
      CONCLUSIONS: These results demonstrate that (a) entomopathogenic fungi strongly
      impact survival and sugar-feeding propensity of both sexes of the malaria vector
      An. gambiae but do not affect their potential to feed and digest meals, and (b)
      that plant sugar sources can be targeted as fungal delivery substrates. In
      addition, targeting males for population reduction using entomopathogenic fungi
      opens up a new strategy for mosquito vector control.

PMID- 25600413
TI  - Structural and functional analysis of two universal stress proteins YdaA and YnaF
      from Salmonella typhimurium: possible roles in microbial stress tolerance.
AB  - In many organisms "Universal Stress Proteins" (USPs) are induced in response to a
      variety of environmental stresses. Here we report the structures of two USPs,
      YnaF and YdaA from Salmonella typhimurium determined at 1.8A and 2.4A
      resolutions, respectively. YnaF consists of a single USP domain and forms a
      tetrameric organization stabilized by interactions mediated through chloride
      ions. YdaA is a larger protein consisting of two tandem USP domains. Two
      protomers of YdaA associate to form a structure similar to the YnaF tetramer.
      YdaA showed ATPase activity and an ATP binding motif G-2X-G-9X-G(S/T/N) was found
      in its C-terminal domain. The residues corresponding to this motif were not
      conserved in YnaF although YnaF could bind ATP. However, unlike YdaA, YnaF did
      not hydrolyse ATP in vitro. Disruption of interactions mediated through chloride
      ions by selected mutations converted YnaF into an ATPase. Residues that might be
      important for ATP hydrolysis could be identified by comparing the active sites of
      native and mutant structures. Only the C-terminal domain of YdaA appears to be
      involved in ATP hydrolysis. The structurally similar N-terminal domain was found
      to bind a zinc ion near the segment equivalent to the phosphate binding loop of
      the C-terminal domain. Mass spectrometric analysis showed that YdaA might bind a
      ligand of approximate molecular weight 800daltons. Structural comparisons suggest
      that the ligand, probably related to an intermediate in lipid A biosynthesis,
      might bind at a site close to the zinc ion. Therefore, the N-terminal domain of
      YdaA binds zinc and might play a role in lipid metabolism. Thus, USPs appear to
      perform several distinct functions such as ATP hydrolysis, altering membrane
      properties and chloride sensing. 

PMID- 25600412
TI  - Evidence of compositional and ultrastructural shifts during the development of
      calcareous tubes in the biofouling tubeworm, Hydroides elegans.
AB  - The serpulid tubeworm, Hydroides elegans, is an ecologically and economically
      important species whose biology has been fairly well studied, especially in the
      context of larval development and settlement on man-made objects (biofouling).
      Nevertheless, ontogenetic changes associated with calcareous tube composition and
      structures have not yet been studied. Here, the ultrastructure and composition of
      the calcareous tubes built by H. elegans was examined in the three early
      calcifying juvenile stages and in the adult using XRD, FTIR, ICP-OES, SEM and
      Raman spectroscopy. Ontogenetic shifts in carbonate mineralogy were observed, for
      example, juvenile tubes contained more amorphous calcium carbonate and were
      predominantly aragonitic whereas adult tubes were bimineralic with considerably
      more calcite. The mineral composition gradually shifted during the tube
      development as shown by a decrease in Sr/Ca and an increase of Mg/Ca ratios with
      the tubeworm's age. The inner tube layer contained calcite, whereas the outer
      layer contained aragonite. Similarly, the tube complexity in terms of
      ultrastructure was associated with development. The sequential appearance of
      unoriented ultrastructures followed by oriented ultrastructures may reflect the
      evolutionary history of serpulid tube biominerals. As aragonitic structures are
      more susceptible to dissolution under ocean acidification (OA) conditions but are
      more difficult to be removed by anti-fouling treatments, the early developmental
      stages of the tubeworms may be vulnerable to OA but act as the important target
      for biofouling control. 

PMID- 25600414
TI  - Adoption, use, and impact of e-booking in private medical practices: mixed
      methods evaluation of a two-year showcase project in Canada.
AB  - BACKGROUND: Managing appointments in private medical practices and ambulatory
      care settings is a complex process. Various strategies to reduce missed
      appointments can be implemented. E-booking systems, which allow patients to
      schedule and manage medical appointments online, represents such a strategy. To
      better support clinicians seeking to offer an e-booking service to their
      patients, health authorities in Canada recently invested in a showcase project
      involving six private medical clinics. OBJECTIVE: The objectives pursued in this
      study were threefold: (1) to measure adoption and use of the e-booking system in
      each of the clinics over a 2-year period, (2) to assess patients' perceptions
      regarding the characteristics and benefits of using the system, and (3) to
      measure the impact of the e-booking system on the number of missed appointments
      in each clinic. METHODS: A mixed-methods approach was adopted in this study. We
      first extracted and analyzed raw data from the e-booking system deployed in each
      of the medical practices to monitor adoption and use of the system over time and
      to assess the impact of the system on the number of missed appointments. Second,
      we conducted a Web-based survey of patients' perceptions in the spring of 2013.
      RESULTS: The patients and physicians targeted by this showcase project showed a
      growing interest in the e-booking system as the number of users, time slots made
      available by physicians, and online appointments grew steadily over time. The
      great majority of patients said that they appreciated the system mainly because
      of the benefits they derived from it, namely, scheduling flexibility, time
      savings, and automated reminders that prevented forgotten appointments.
      Importantly, our findings suggest that the system's automated reminders help
      significantly reduce the number of missed appointments. CONCLUSIONS: E-booking
      systems seem to represent a win-win solution for patients and physicians in
      private medical practices. We encourage researchers to replicate and extend our
      work in other primary care settings in order to test the generalizability of our
      findings.

PMID- 25600415
TI  - Prevalence and treatment of chronic hepatitis C virus infection in the US
      Department of Veterans Affairs.
AB  - Chronic hepatitis C virus (HCV) is the most common blood-borne pathogen in the
      United States. HCV disproportionately affects Veterans Affairs (VA) health-care
      users: 174,302 HCV-infected veterans were in VA care in 2013, making the VA the
      world's largest HCV care provider. This systematic review identified 546 articles
      related to HCV in the VA. After assessment by 2 independent reviewers, 28
      articles describing prevalence and treatment of HCV in VA users ultimately met
      inclusion criteria. Most VA patients currently living with HCV infection were
      born between 1945 and 1965 and were infected with HCV between 1970 and 1990. To
      prevent HCV-related complications such as cirrhosis, hepatocellular carcinoma,
      and death, medical personnel must identify and treat HCV. However, antiviral
      therapy has historically been limited by medication side effects,
      contraindications, and patient acceptance. Although treatment initiation rates
      are higher in the VA than in the general United States, only 23% of VA HCV
      patients have received treatment and, of those, only a minority were cured.
      Recent development of more effective and tolerable antiviral agents represents a
      major pharmacological breakthrough. Eradication of HCV is theoretically possible
      for the majority of HCV patients for the first time, although new barriers, such
      as high drug costs, may limit future uptake. 

PMID- 25600416
TI  - Prevalence of mental health disorders among justice-involved veterans.
AB  - Justice-involved veterans are a special population with unique mental health
      needs compared with other veterans or justice-involved adults. Prevalence
      estimates of mental health concerns of justice-involved veterans across 18
      samples of these veterans (1987-2013), including both incarcerated and community
      samples, were identified through a systematic literature search of published
      studies supplemented by Department of Veterans Affairs Veterans Justice Programs
      data. Despite heterogeneity across samples and measures used, the review
      highlights several prominent mental health concerns among veterans. Many justice
      involved veterans have likely experienced at least one traumatic event, and many
      have post-traumatic stress disorder (prevalence from 4% to 39% across samples).
      At least half of justice-involved veterans have an alcohol and/or drug use
      disorder (estimates as high as 71% and 65%, respectively), and other psychiatric
      disorders, such as depression (14%-51%) and psychotic disorders (4%-14%), are
      common. Justice-involved veterans with comorbid substance use and psychiatric
      disorders are at increased risk of negative outcomes, including homelessness and
      violent behavior. Overall, comparisons of justice-involved veterans with other
      justice-involved adults found a slightly higher rate of mental health concerns
      among justice-involved veterans, with some indication that intravenous drug use
      is more prevalent. Compared with other veterans, justice-involved veterans have
      consistently higher rates of mental health concerns, particularly substance use
      disorders. 

PMID- 25600417
TI  - Hearing impairment and tinnitus: prevalence, risk factors, and outcomes in US
      service members and veterans deployed to the Iraq and Afghanistan wars.
AB  - Hearing loss and tinnitus are the 2 most prevalent service-connected disabilities
      among veterans in the United States. Veterans of Operations Enduring Freedom,
      Iraqi Freedom, and New Dawn have been exposed to multiple hazards associated with
      these conditions, such as blasts/explosions, ototoxic chemicals, and most notably
      high levels of noise. We conducted a systematic literature review of evidence on
      1) prevalence of, 2) risk and protective factors for, and 3) functional and
      quality-of-life outcomes of hearing impairment and tinnitus in US Operations
      Enduring Freedom, Iraqi Freedom, and New Dawn veterans and military personnel. We
      identified studies published from 2001 through 2013 using PubMed, PsycINFO,
      REHABDATA, Cochrane Library, pearling, and expert recommendation. Peer-reviewed
      English language articles describing studies of 30 or more adults were included
      if they informed one or more key questions. A total of 839 titles/abstracts were
      reviewed for relevance by investigators trained in critical analysis of
      literature; 14 studies met inclusion criteria. Of these, 13 studies presented
      data on prevalence and 4 on risk/protective factors, respectively. There were no
      included studies reporting on outcomes. Findings from this systematic review will
      help inform clinicians, researchers, and policy makers on future resource and
      research needs pertaining to hearing impairment and tinnitus in this newest
      generation of veterans. 

PMID- 25600418
TI  - Source tracking swine fecal waste in surface water proximal to swine concentrated
      animal feeding operations.
AB  - Swine farming has gone through many changes in the last few decades, resulting in
      operations with a high animal density known as confined animal feeding operations
      (CAFOs). These operations produce a large quantity of fecal waste whose
      environmental impacts are not well understood. The purpose of this study was to
      investigate microbial water quality in surface waters proximal to swine CAFOs
      including microbial source tracking of fecal microbes specific to swine. For one
      year, surface water samples at up- and downstream sites proximal to swine CAFO
      lagoon waste land application sites were tested for fecal indicator bacteria
      (fecal coliforms, Escherichia coli and Enterococcus) and candidate swine-specific
      microbial source-tracking (MST) markers (Bacteroidales Pig-1-Bac, Pig-2-Bac, and
      Pig-Bac-2, and methanogen P23-2). Testing of 187 samples showed high fecal
      indicator bacteria concentrations at both up- and downstream sites. Overall, 40%,
      23%, and 61% of samples exceeded state and federal recreational water quality
      guidelines for fecal coliforms, E. coli, and Enterococcus, respectively. Pig-1
      Bac and Pig-2-Bac showed the highest specificity to swine fecal wastes and were
      2.47 (95% confidence interval [CI]=1.03, 5.94) and 2.30 times (95% CI=0.90, 5.88)
      as prevalent proximal down- than proximal upstream of swine CAFOs, respectively.
      Pig-1-Bac and Pig-2-Bac were also 2.87 (95% CI=1.21, 6.80) and 3.36 (95% CI=1.34,
      8.41) times as prevalent when 48 hour antecedent rainfall was greater than versus
      less than the mean, respectively. Results suggest diffuse and overall poor
      sanitary quality of surface waters where swine CAFO density is high. Pig-1-Bac
      and Pig-2-Bac are useful for tracking off-site conveyance of swine fecal wastes
      into surface waters proximal to and downstream of swine CAFOs and during rain
      events.

PMID- 25600419
TI  - Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental
      growth factor ratio: an inter-assay comparison.
AB  - The angiogenic factor ratio soluble Fms-kinase 1 (sFlt-1)/placental growth factor
      (PlGF) is a novel diagnostic tool for preeclampsia. We compared the efficacy of
      the KRYPTOR (BRAHMS) automated assays for sFlt-1 and PlGF with the Elecsys
      (Roche) assays in a routine clinical setting. Preeclamptic women (n = 39) were
      included shortly after the time of diagnosis. Normotensive control pregnancies
      were matched by gestational age (n = 76). The KRYPTOR assays performed comparably
      or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; P =
      .09; for non-obese 0.820 versus 0.805, P = .047). For early-onset preeclampsia,
      KRYPTOR area under the curve increased to 0.929 with a 100% specificity for
      preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off
      33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver
      enzymes, Low Platelet count (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was
      manifold increased (P < .01). The sFlt-1/PlGF ratio proved especially useful in
      early-onset preeclampsia, preeclampsia with preterm delivery or HELLP, and among
      non-obese women. 

PMID- 25600420
TI  - Comparison of an in-pharmacy automated blood pressure kiosk to daytime ambulatory
      blood pressure in hypertensive subjects.
AB  - The objective of this study was to compare serial readings from an in-pharmacy
      automated blood pressure (BP) kiosk to mean daytime ambulatory BP. A total of 100
      community-dwelling adults with hypertension underwent (1) three baseline
      automated office readings; (2) three in-pharmacy readings on each of four visits
      (12 total) using the PharmaSmart PS-2000 kiosk; and (3) 24-hour ambulatory BP
      monitoring between in-pharmacy visits two and three. Paired t-tests, Bland-Altman
      plots, and Pearson correlation coefficients were used for analysis. Mean BPs were
      137.8 +/- 13.7/81.9 +/- 12.2 mm Hg for in-pharmacy and 135.5 +/- 11.7/79.7 +/-
      10.0 mm Hg for daytime ambulatory (difference of 2.3 +/- 9.5/2.2 +/- 6.9 mm Hg [P
      <= .05]). Bland-Altman plots depicted a high degree of BP variability but did not
      show clinically important systematic BP differences. With ambulatory BP as the
      reference standard, in-pharmacy device results were similar to automated office
      results. The PharmaSmart PS-2000 closely approximated mean daytime ambulatory BP,
      supporting the use of serial readings from this device in the assessment of BP. 

PMID- 25600422
TI  - Genetic and environmental influences underlying the relationship between autistic
      traits and temperament and character dimensions in adulthood.
AB  - BACKGROUND: In recent years, several twin studies adopted a dimensional approach
      to Autism Spectrum Disorders (ASD) and estimated the contribution of genetic and
      environmental influences to variation in autistic traits. However, no study was
      performed on adults over 18 years of age and all but two studies were based on
      parent or teacher ratings. Also, the genetic and environmental contributions to
      the interplay between autistic traits and adult personality dimensions have not
      been investigated. METHODS: A sample of 266 complete twin pairs (30% males, mean
      age 40 +/- 12 years) drawn from the population-based Italian Twin Register was
      administered the Autism-Spectrum Quotient, Temperament and Character Inventory
      (TCI-125), and General Health Questionnaire (GHQ-12). Genetic structural equation
      modelling was performed with the Mx program. Estimates were adjusted for gender,
      age, and GHQ-12 score. RESULTS: Genetic factors accounted for 44% and 20%-49% of
      individual differences in autistic traits and TCI dimensions, respectively.
      Unshared environmental factors explained the remaining proportion of variance.
      Consistently with the notion of a personality profile in ASD characterised by
      obsessive temperament, autistic traits showed significant phenotypic correlations
      with several TCI dimensions (positive: HA; negative: NS, RD, SD, C). Genetic and
      unshared environmental correlations between AQ and these TCI dimensions were
      significant. The degree of genetic overlap was generally greater than the degree
      of environmental overlap. CONCLUSIONS: Despite some limitations, this study
      suggests that genetic factors contribute substantially to individual differences
      in autistic traits in adults, with unshared environmental influences also playing
      an important role. It also suggests that autistic traits and the majority of
      temperament and character dimensions share common genetic and environmental
      aetiological factors.

PMID- 25600421
TI  - Regional, age and sex differences in baseline characteristics of patients
      enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin
      (TECOS).
AB  - AIMS: To report baseline characteristics and cardiovascular (CV) risk management
      by region, age, sex and CV event type for 14 724 participants in the Trial
      Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, double
      blind, placebo-controlled trial exploring whether sitagliptin added to usual type
      2 diabetes (T2DM) care affects time to first event in the composite endpoint of
      CV death, non-fatal myocardial infarction (MI), non-fatal stroke or unstable
      angina hospitalization. METHODS: TECOS enrolled patients aged >=50 years, with
      T2DM and CV disease from 38 countries in five regions: North America, Eastern
      Europe, Western Europe, Asia Pacific and Latin America. Participants had a
      glycated haemoglobin concentration of 6.5-8.0% (48-64 mmol/mol) and were
      receiving oral and/or insulin-based antihyperglycaemic therapy. Analysis of
      variance or logistic regression was used to compare regional CV risk factors and
      treatments, referenced to North America. RESULTS: Patients had a mean [1 standard
      deviation (SD)] age of 66 (8) years, a median (interquartile range) diabetes
      duration of 9.4 (4.9, 15.3) years, and a mean (SD) body mass index 30.2 (5.7)
      kg/m2 . Compared with North America, blood pressure and lipids were higher in all
      regions. Statin use was lowest in Latin America (68%) and Eastern Europe (70%)
      and aspirin use was lower compared with North America in all regions except Asia
      Pacific. Achievement of treatment targets did not differ by age group or insulin
      usage, but men and participants with previous MI were more likely than women or
      those with previous stroke or peripheral arterial disease to reach most treatment
      goals. CONCLUSION: The CV risk factors of participants in TECOS are reasonably
      controlled, but differences in CV risk management according to region, sex and
      history of disease exist. This diversity will enhance the generalizability of the
      trial results.

PMID- 25600423
TI  - Differential lexical correlates of social cognition and metacognition in
      schizophrenia; a study of spontaneously-generated life narratives.
AB  - OBJECTIVES: Social cognition and metacognition have been identified as important
      cognitive domains in schizophrenia, which are separable from general
      neurocognition and predictive of functional and treatment outcomes. However, one
      challenge to improved models of schizophrenia has been the conceptual overlap
      between the two. One tool used in previous research to develop cognitive models
      of psychopathology is language analysis. In this article we aimed to clarify
      distinctions between social cognition and metacognition in schizophrenia using
      computerized language software. METHODS: Fifty-eight (n=58) individuals with
      schizophrenia completed the Metacognitive Assessment Scale Abbreviated and
      measures of social cognition using the Hinting, Eyes, BLERT and Picture
      Arrangement test. A lexical analysis of participants' speech using Language
      Inquiry and Word Count software was conducted to examine relative frequencies of
      word types. Lexical characteristics were examined for their relationships to
      social cognition and metacognition. RESULTS: We found that lexical
      characteristics indicative of cognitive complexity were significantly related to
      level of metacognitive capacity while social cognition was related to second
      person pronoun use, articles, and prepositions, and pronoun use overall. The
      relationships between lexical variables and metacognition persisted after
      controlling for demographics, verbal intelligence, and overall word count, but
      the same was not true for social cognition. CONCLUSIONS: Our findings provided
      support for the view that metacognition requires more synthetic and complex
      verbal and linguistic operations, while social cognition is associated with the
      representation and clear identification of others.

PMID- 25600425
TI  - CORRIGENDUM: Computational Study of In-Plane Phonon Transport in Si Thin Films.

PMID- 25600424
TI  - Clinical decision making and outcome in the routine care of people with severe
      mental illness across Europe (CEDAR).
AB  - AIMS: Shared decision making has been advocated as a means to improve patient
      orientation and quality of health care. There is a lack of knowledge on clinical
      decision making and its relation to outcome in the routine treatment of people
      with severe mental illness. This study examined preferred and experienced
      clinical decision making from the perspectives of patients and staff, and how
      these affect treatment outcome. METHODS: "Clinical Decision Making and Outcome in
      Routine Care for People with Severe Mental Illness" (CEDAR; ISRCTN75841675) is a
      naturalistic prospective observational study with bimonthly assessments during a
      12-month observation period. Between November 2009 and December 2010, adults with
      severe mental illness were consecutively recruited from caseloads of community
      mental health services at the six study sites (Ulm, Germany; London, UK; Naples,
      Italy; Debrecen, Hungary; Aalborg, Denmark; and Zurich, Switzerland). Clinical
      decision making was assessed using two instruments which both have parallel
      patient and staff versions: (a) The Clinical Decision Making Style Scale (CDMS)
      measured preferences for decision making at baseline; and (b) the Clinical
      Decision Making Involvement and Satisfaction Scale (CDIS) measured involvement
      and satisfaction with a specific decision at all time points. Primary outcome was
      patient-rated unmet needs measured with the Camberwell Assessment of Need Short
      Appraisal Schedule (CANSAS). Mixed-effects multinomial regression was used to
      examine differences and course over time in involvement in and satisfaction with
      actual decision making. The effect of clinical decision making on the primary
      outcome was examined using hierarchical linear modelling controlling for
      covariates (study centre, patient age, duration of illness, and diagnosis).
      Analysis were also controlled for nesting of patients within staff. RESULTS: Of
      708 individuals approached, 588 adults with severe mental illness (52% female,
      mean age = 41.7) gave informed consent. Paired staff participants (N = 213) were
      61.8% female and 46.0 years old on average. Shared decision making was preferred
      by patients (chi 2 = 135.08; p < 0.001) and staff (chi 2 = 368.17; p < 0.001).
      Decision making style of staff significantly affected unmet needs over time, with
      unmet needs decreasing more in patients whose clinicians preferred active to
      passive (-0.406 unmet needs per two months, p = 0.007) or shared (-0.303 unmet
      needs per two months, p = 0.015) decision making. CONCLUSIONS: Decision making
      style of staff is a prime candidate for the development of targeted intervention.
      If proven effective in future trials, this would pave the ground for a shift from
      shared to active involvement of patients including changes to professional
      socialization through training in principles of active decision making.

PMID- 25600426
TI  - Coping with work and family: how do dual-earners interact?
AB  - Juggling the demands of both work and family has become increasingly difficult,
      especially for dual-earner households; nevertheless, families have developed
      strategies to deal with work-family challenges. This paper uses couple level
      analyses (APIM models) with 100 dual-earner couples to provide insight about
      partners' mutual influence on the use of work-family coping strategies. The
      results show that women's use of coping strategies is more associated with work
      family conflict and work-family enrichment than men's coping. In addition, using
      partner coping, having a positive attitude towards multiple roles, using planning
      and management skills and avoiding having to cut back on professional
      responsibilities is associated with better outcomes (more enrichment and less
      conflict). Surprisingly, the use of childcare facilities is associated with
      women's conflict and partner effects were only found concerning the use of
      management and planning skills. These skills, however, have distinct effects for
      men and women's outcomes: their use by men reduces their own conflict but
      increases their wives', while their use by women decreases their own conflict and
      increases their own and their partner's enrichment. These results point to the
      fact that gender roles continue to be a hallmark of work-family issues. Our
      design and results point out the need for new interventions that take couple
      interdependences into account. 

PMID- 25600427
TI  - Pro-inflammatory properties of shark cartilage supplement.
AB  - The erosion and breakdown of cartilage is generally recognized to be an integral
      manifestation of arthritic disease, which is often accompanied by the development
      and progression of inflammation associated with it. Commercial shark cartilage
      (SC) is a popular dietary supplement taken for the prevention and/or control of
      chronic disease, including arthritis. The efficacy of SC in maintaining joint
      health remains questionable; there is a lack of sufficient reliable information
      on its effect on immunocompetent cells, and the potential health risks involved
      have not been adequately assessed. Our earlier in vitro studies showed that SC
      extracts induce a Th1-type inflammatory cytokine response in human leucocytes,
      and collagen type II alpha 1 protein was shown to be an active cytokine-inducing
      component in SC. In this study, we further define the cellular response to SC
      stimulation by classifying leucocytes into primary and secondary responders
      employing enriched leucocyte subpopulations. Inhibitors of specific signaling
      pathways were used to verify the functional effect of SC on specific pathway(s)
      utilized. Results indicate the monocyte/macrophage as the initially responding
      cell, followed by lymphocytes and the production of interferon-gamma. Chemokines,
      MCP-1 and RANTES, were produced at significant levels in stimulated leucocyte
      cultures. Initial cellular activation is likely followed by activation of Jun
      Kinase and p38 mitogen-activated protein kinase signal transduction pathways.
      This study presents evidence of significant immunological reactivity of
      components of commercial SC supplement, which could pose a potential health risk
      for consumers, particularly those with underlying inflammatory disease such as
      irritable bowel syndrome and arthritis. 

PMID- 25600428
TI  - Genomic copy number alterations of primary and secondary metastasizing
      pleomorphic adenomas.
AB  - AIMS: Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism
      of metastasis still is unknown. To date, there has been no study on MPA genomics.
      We analysed primary and secondary MPAs with array comparative genomic
      hybridization to identify somatic copy number alterations and affected genes.
      METHODS AND RESULTS: Tumour DNA samples from primary (parotid salivary gland) and
      secondary (scalp skin) MPAs were subjected to array comparative genomic
      hybridization investigation, and the data were analysed with NEXUS COPY NUMBER
      DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and
      19p13.3p123, and a complex pattern of four different deletions at chromosome 6.
      The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among
      others. The secondary MPA showed a genomic profile similar to that of the primary
      MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1
      (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). CONCLUSION: Our findings
      indicated a clonal origin of the secondary MPA, as both tumours shared a common
      profile of genomic copy number alterations. Furthermore, we were able to detect
      in the primary tumour a specific pattern of copy number alterations that could
      explain the metastasizing characteristic, whereas the secondary MPA showed a more
      unbalanced genome.

PMID- 25600433
TI  - Spin canting, metamagnetism, and single-chain magnetic behaviour in a cyano
      bridged homospin iron(II) compound.
AB  - Spin canting, antiferromagnetic ordering, metamagnetism and single-chain
      magnetism were verified in a cyano-bridged Fe(II) compound synthesized from the
      pentagonal bipyramidal Fe(II) starting material in the presence of excessive BF4(
      ) anions. 

PMID- 25600432
TI  - The role of perioperative antiplatelet therapy and platelet reactivity testing in
      carotid revascularization: overview of the evidence.
AB  - Antiplatelet therapy has reduced the incidence of thromboembolic events for
      patients undergoing carotid revascularization. However, the platelet inhibitory
      effect of aspirin and clopidogrel, the most commonly used P2Y12 receptor
      inhibitors, is variable among patients. Patients displaying high platelet
      reactivity despite aspirin or clopidogrel treatment are at higher risk for
      thromboembolic events during and after carotid revascularization. In order to
      reduce the incidence of high platelet reactivity, more potent P2Y12 receptor
      inhibitors as prasugrel are used. However, this strategy increases the risk of
      bleeding. As there is evidence of a therapeutic window for platelet inhibition,
      platelet function tests could be helpful for tailoring antiplatelet therapy based
      on the patient's thrombotic and bleeding risk. This evidence overview describes
      the most commonly used platelet inhibitors, platelet function tests and the
      current evidence for tailoring of antiplatelet therapy to patients undergoing
      carotid revascularization. 

PMID- 25600429
TI  - The spinal anti-inflammatory mechanism of motor cortex stimulation: cause of
      success and refractoriness in neuropathic pain?
AB  - BACKGROUND: Motor cortex stimulation (MCS) is an effective treatment in
      neuropathic pain refractory to pharmacological management. However, analgesia is
      not satisfactorily obtained in one third of patients. Given the importance of
      understanding the mechanisms to overcome therapeutic limitations, we addressed
      the question: what mechanisms can explain both MCS effectiveness and
      refractoriness? Considering the crucial role of spinal neuroimmune activation in
      neuropathic pain pathophysiology, we hypothesized that modulation of spinal
      astrocyte and microglia activity is one of the mechanisms of action of MCS.
      METHODS: Rats with peripheral neuropathy (chronic nerve injury model) underwent
      MCS and were evaluated with a nociceptive test. Following the test, these animals
      were divided into two groups: MCS-responsive and MCS-refractory. We also
      evaluated a group of neuropathic rats not stimulated and a group of sham-operated
      rats. Some assays included rats with peripheral neuropathy that were treated with
      AM251 (a cannabinoid antagonist/inverse agonist) or saline before MCS. Finally,
      we performed immunohistochemical analyses of glial cells (microglia and
      astrocytes), cytokines (TNF-alpha and IL-1beta), cannabinoid type 2 (CB2), MU
      opioid (MOR), and purinergic P2X4 receptors in the dorsal horn of the spinal cord
      (DHSC). FINDINGS: MCS reversed mechanical hyperalgesia, inhibited astrocyte and
      microglial activity, decreased proinflammatory cytokine staining, enhanced CB2
      staining, and downregulated P2X4 receptors in the DHSC ipsilateral to sciatic
      injury. Spinal MOR staining was also inhibited upon MCS. Pre-treatment with AM251
      blocked the effects of MCS, including the inhibitory mechanism on cells. Finally,
      MCS-refractory animals showed similar CB2, but higher P2X4 and MOR staining
      intensity in the DHSC in comparison to MCS-responsive rats. CONCLUSIONS: These
      results indicate that MCS induces analgesia through a spinal anti
      neuroinflammatory effect and the activation of the cannabinoid and opioid systems
      via descending inhibitory pathways. As a possible explanation for MCS
      refractoriness, we propose that CB2 activation is compromised, leading to
      cannabinoid resistance and consequently to the perpetuation of neuroinflammation
      and opioid inefficacy.

PMID- 25600431
TI  - Atrial pacing during radiofrequency deliveries for catheter ablation of para
      Hisian arrhythmias.
AB  - BACKGROUND: Atrial pacing during radiofrequency (RF) deliveries is a technique to
      facilitate rapid recognition of impaired atrioventricular (AV) conduction during
      slow pathway ablation of AV nodal reentrant tachycardia. The objective of our
      study was to report this technique in the catheter ablation of para-Hisian
      arrhythmias. METHODS: The study included a total of 48 patients who underwent
      ablation of para-Hisian arrhythmias including accessory pathways (APs), atrial
      tachycardias (ATs), and ventricular arrhythmias (VAs) in 6, 9, and 33 patients,
      respectively. RESULTS: AT was successfully eliminated in all cases without any
      accelerated junctional rhythm (JR) occurring. JR appeared during RF deliveries in
      20 patients (3 with APs, 17 with VAs). In 11 of 20 patients, RF deliveries were
      terminated when JR appeared and restarted during atrial pacing at a faster rate
      than the JR. No transient complete AV block was observed in the 11 patients,
      however it occurred in 1 of the remaining 9 without atrial pacing (p=0.25). Small
      His bundle potentials were recorded at the effective ablation site before the RF
      delivery in 11 (55%) patients. No patients had any AV conduction disturbances at
      the end of and after the procedure. APs were successfully eliminated in 2 of 3
      patients. VAs were completely and partially eliminated in 10 and 4 of 17
      patients, respectively. CONCLUSIONS: Atrial pacing during RF applications might
      be helpful to avoid AV conduction disturbances during catheter ablation of APs
      close to the His bundle and idiopathic VAs originating in the vicinity of the His
      bundle.

PMID- 25600430
TI  - The association of beta-2 adrenoceptor genotype with short-cervix mediated
      preterm birth: a case-control study.
AB  - OBJECTIVE: To determine whether beta2 -adrenoceptor (beta2 AR) genotype is
      associated with shortening of the cervix or with preterm birth (PTB) risk among
      women with a short cervix in the second trimester. DESIGN: A case-control
      ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen
      participating centres of the Maternal-Fetal Medicine Units Network of the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development.
      POPULATION: Four hundred thirty-nine women, including 315 with short cervix and
      124 with normal cervical length. METHODS: Nulliparous women with cervical length
      <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for
      race/ethnicity with cervical lengths >=40 mm were studied. beta2 AR genotype was
      determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME
      MEASURES: Genotype distributions were compared between case and control groups.
      Within the short cervix group, pregnancy outcomes were compared by genotype, with
      a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at
      position 16 for 433 women and at position 27 for 437. Using a recessive model
      testing for association between short cervix and genotype, and adjusted for
      ethnicity, there was no statistical difference between cases and controls for
      Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI
      0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from
      PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk,
      although sample size was limited. CONCLUSIONS: beta2 AR genotype does not seem to
      be associated with short cervical length or with PTB following the second
      trimester identification of a short cervix. Influences on PTB associated with
      beta2 AR genotype do not appear to involve a short cervix pathway.

PMID- 25600434
TI  - Epimerization at C-3'' in butirosin biosynthesis by an NAD(+) -dependent
      dehydrogenase BtrE and an NADPH-dependent reductase BtrF.
AB  - Butirosin is an aminoglycoside antibiotic consisting two epimers at C-3'' of
      ribostamycin/xylostasin with a unique 4-amino-2-hydroxybutyrate moiety at C-1 of
      the aminocyclitol 2-deoxystreptamine (2DOS). To date, most of the enzymes encoded
      in the biosynthetic gene cluster for butirosin, from the producing strain
      Bacillus circulans, have been characterized. A few unknown functional proteins,
      including nicotinamide adenine dinucleotide cofactor-dependent
      dehydrogenase/reductase (BtrE and BtrF), are supposed to be involved in the
      epimerization at C-3'' of butirosin B/ribostamycin but remain to be
      characterized. Herein, the conversion of ribostamycin to xylsostasin by BtrE and
      BtrF in the presence of NAD(+) and NADPH was demonstrated. BtrE oxidized the C
      3'' of ribostamycin with NAD(+) to yield 3''-oxoribostamycin. BtrF then reduced
      the generated 3''-oxoribostamycin with NADPH to produce xylostasin. This reaction
      step was the last piece of butirosin biosynthesis to be described. 

PMID- 25600435
TI  - Epidemiological analysis of a large enterohaemorrhagic Escherichia coli O111
      outbreak in Japan associated with haemolytic uraemic syndrome and acute
      encephalopathy.
AB  - A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) O111 and O157
      occurred in Japan in April 2011. We conducted an unmatched case-control study and
      trace-back investigation to determine the source of EHEC O111 infection and risk
      factors for severe complications. Pulsed-field gel electrophoresis was performed
      to help define cases. A total of 86 individuals met the case definition. Of
      these, 40% experienced haemolytic uraemic syndrome (HUS), 24% acute
      encephalopathy, and 6% died. Illness was significantly associated with eating the
      raw beef dish yukhoe (odds ratio 19.64, 95% confidence interval 7.03-54.83), the
      likely food vehicle. EHEC O111 and its closely related stx-negative variants were
      found in the beef. HUS occurred most frequently in individuals aged 5-9 years,
      and this age group was significantly associated with acute encephalopathy. The
      prevalence of HUS and acute encephalopathy was higher than in previous non-O157
      related outbreaks, indicating a high risk of severe complications. 

PMID- 25600437
TI  - Fine-tuning Tumor Immunity with Integrin Trans-regulation.
AB  - Inefficient T-cell homing to tissues limits adoptive T-cell immunotherapy of
      solid tumors. alphaLbeta2 and alpha4beta1 integrins mediate trafficking of T
      cells into tissues via engagement of ICAM-1 and VCAM-1, respectively. Inhibiting
      protein kinase A (PKA)-mediated phosphorylation of alpha4 integrin in cells
      results in an increase in alphaLbeta2-mediated migration on mixed ICAM-1-VCAM-1
      substrates in vitro, a phenomenon termed "integrin trans-regulation." Here, we
      created an alpha4(S988A)-bearing mouse, which precludes PKA-mediated alpha4
      phosphorylation, to examine the effect of integrin trans-regulation in vivo. The
      alpha4(S988A) mouse exhibited a dramatic and selective increase in migration of
      lymphocytes, but not myeloid cells, to sites of inflammation. Importantly, we
      found that the alpha4(S988A) mice exhibited a marked increase in T-cell entry
      into and reduced growth of B16 melanomas, consistent with antitumor roles of
      infiltrating T cells and progrowth functions of tumor-associated macrophages.
      Thus, increased alpha4 trans-regulation of alphaLbeta2 integrin function biases
      leukocyte emigration toward lymphocytes relative to myeloid cells and enhances
      tumor immunity.

PMID- 25600436
TI  - Identification of chimeric antigen receptors that mediate constitutive or
      inducible proliferation of T cells.
AB  - This study compared second-generation chimeric antigen receptors (CAR) encoding
      signaling domains composed of CD28, ICOS, and 4-1BB (TNFRSF9). Here, we report
      that certain CARs endow T cells with the ability to undergo long-term autonomous
      proliferation. Transduction of primary human T cells with lentiviral vectors
      encoding some of the CARs resulted in sustained proliferation for up to 3 months
      following a single stimulation through the T-cell receptor (TCR). Sustained
      numeric expansion was independent of cognate antigen and did not require the
      addition of exogenous cytokines or feeder cells after a single stimulation of the
      TCR and CD28. Results from gene array and functional assays linked sustained
      cytokine secretion and expression of T-bet (TBX21), EOMES, and GATA-3 to the
      effect. Sustained expression of the endogenous IL2 locus has not been reported in
      primary T cells. Sustained proliferation was dependent on CAR structure and high
      expression, the latter of which was necessary but not sufficient. The mechanism
      involves constitutive signaling through NF-kappaB, AKT, ERK, and NFAT. The
      propagated CAR T cells retained a diverse TCR repertoire, and cellular
      transformation was not observed. The CARs with a constitutive growth phenotype
      displayed inferior antitumor effects and engraftment in vivo. Therefore, the
      design of CARs that have a nonconstitutive growth phenotype may be a strategy to
      improve efficacy and engraftment of CAR T cells. The identification of CARs that
      confer constitutive or nonconstitutive growth patterns may explain observations
      that CAR T cells have differential survival patterns in clinical trials.

PMID- 25600440
TI  - Measurement of dabigatran plasma concentrations by calibrated thrombin clotting
      time in comparison to LC-MS/MS in human volunteers on dialysis.
AB  - INTRODUCTION: Dabigatran etexilate is an oral direct thrombin inhibitor. Although
      routine anticoagulation monitoring with dabigatran is not usually required, a
      simple and precise laboratory test to measure dabigatran concentrations in
      patient plasma may be useful in certain clinical circumstances, such as emergency
      situations. The HEMOCLOT((r)) Thrombin Inhibitors assay has demonstrated accurate
      and precise determination of dabigatran concentrations within a range of 50-500
      ng/ml. The objective of this study was to assess comparability of dabigatran
      concentrations determined by HEMOCLOT((r)) and by liquid chromatography/tandem
      mass spectrometry (LC-MS/MS) in plasma samples from human volunteers with end
      stage renal disease (ESRD) undergoing regular haemodialysis (HD) during a Phase I
      study. MATERIALS AND METHODS: Overall, 304 plasma samples were obtained from
      seven ESRD patients in dabigatran steady-state for measurement by HEMOCLOT((r))
      (calibrated diluted thrombin time [dTT]) and by LC-MS/MS. Agreement of dabigatran
      concentrations was assessed by regression analysis and difference plots. RESULTS:
      The measurements of calibration standards of the HEMOCLOT((r)) assay showed
      excellent precision with coefficients of variation <5%. Accuracy determined by
      analysis of two quality control samples was 90% and 111%. HEMOCLOT((r))-derived
      dabigatran plasma concentrations paralleled those obtained by LC-MS/MS. The mean
      ratio of the LC-MS/MS and dTT-derived concentrations was 0.955 (67% limits of
      agreement: 0.771-1.18). CONCLUSIONS: The HEMOCLOT((r)) Thrombin Inhibitors assay
      is suitable for measuring dabigatran plasma concentrations in volunteers with
      ESRD undergoing haemodialysis. The agreement between dabigatran concentrations
      determined by the HEMOCLOT((r)) assay and the LC-MS/MS reference method met
      bioanalytical acceptance criteria.

PMID- 25600439
TI  - Genetic evidence that intratumoral T-cell proliferation and activation are
      associated with recurrence and survival in patients with resected colorectal
      liver metastases.
AB  - Though immune responses correlate with prognosis in primary colorectal cancer,
      the role of tumor immunity in metastatic disease is less clear. We hypothesized
      that patient survival and tumor recurrence correlate with transcriptional
      evidence of lymphocyte proliferation/activation in resected colorectal cancer
      liver metastases (CRLM). Microarray gene analysis was performed on liver tumor
      specimens from 96 patients who underwent resection for CRLM. A Cox proportional
      hazards model identified genes associated with overall survival (OS) and
      recurrence-free survival (RFS). Conventional gene ontology (GO) enrichment
      analysis ranked biologically relevant processes. Survival probabilities of
      prioritized processes were assessed. Protein expression was validated with
      immunohistochemistry in an independent set of patients. GO analysis identified
      and ranked unique biologic processes that correlated with survival. Genes that
      specifically functioned in the biologic process of "T-cell proliferation" were
      significant predictors of OS (P = 0.01), and both "T-cell proliferation" and
      "activation" were highly associated with RFS (P <= 0.01). Analysis of genes in
      these GO categories identified increased TNFSF14/LIGHT expression to be most
      associated with improved OS and RFS (P <= 0.0006). Immunohistochemistry of an
      independent validation set of CRLM confirmed that both increased tumor
      infiltrating lymphocytes (TIL) and higher LIGHT expression on TILs were
      associated with improved OS and RFS. Differential expression of genes involved in
      T-cell proliferation/activation was associated with survival outcomes in a large
      number of surgical patients who underwent resection of CRLM. These biologic
      functions determined by GO analysis of the tumor microenvironment have identified
      specific immune-related genes that may be involved in an antitumor immune
      response.

PMID- 25600441
TI  - Normal platelet activation profile in patients with peripheral arterial disease
      on aspirin.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a progressive vascular disease
      associated with a high risk of cardiovascular morbidity and death. Antithrombotic
      prevention is usually applied by prescribing the antiplatelet agent aspirin.
      However, in patients with PAD aspirin fails to provide protection against
      myocardial infarction and death, only reducing the risk of ischemic stroke.
      Platelets may play a role in disease development, but this has not been tested by
      proper mechanistic studies. In the present study, we performed a systematic
      evaluation of platelet reactivity in whole blood from patients with PAD using two
      high-throughput assays, i.e. multi-agonist testing of platelet activation by flow
      cytometry and multi-parameter testing of thrombus formation on spotted
      microarrays. METHODS: Blood was obtained from 40 patients (38 on aspirin) with
      PAD in majority class IIa/IIb and from 40 age-matched control subjects. Whole
      blood flow cytometry and multiparameter thrombus formation under high-shear flow
      conditions were determined using recently developed and validated assays.
      RESULTS: Flow cytometry of whole blood samples from aspirin-treated patients
      demonstrated unchanged high platelet responsiveness towards ADP, slightly
      elevated responsiveness after glycoprotein VI stimulation, and decreased
      responsiveness after PAR1 thrombin receptor stimulation, compared to the control
      subjects. Most parameters of thrombus formation under flow were similarly high
      for the patient and control groups. However, in vitro aspirin treatment caused a
      marked reduction in thrombus formation, especially on collagen surfaces. When
      compared per subject, markers of ADP- and collagen-induced integrin activation
      (flow cytometry) strongly correlated with parameters of collagen-dependent
      thrombus formation under flow, indicative of a common, subject-dependent
      regulation of both processes. CONCLUSION: Despite of the use of aspirin, most
      platelet activation properties were in the normal range in whole-blood from class
      II PAD patients. These data underline the need for more effective antithrombotic
      pharmacoprotection in PAD.

PMID- 25600438
TI  - Requirement for innate immunity and CD90+ NK1.1- lymphocytes to treat established
      melanoma with chemo-immunotherapy.
AB  - We sought to define cellular immune mechanisms of synergy between tumor-antigen
      targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice
      was treated with cytotoxic doses of cyclophosphamide in combination with an
      antibody targeting tyrosinase-related protein 1 (alphaTRP1), a native melanoma
      differentiation antigen. We find that Fcgamma receptors are required for
      efficacy, showing that antitumor activity of combination therapy is immune
      mediated. Rag1(-/-) mice deficient in adaptive immunity are able to clear tumors,
      and thus innate immunity is sufficient for efficacy. Furthermore, previously
      treated wild-type mice are not significantly protected against tumor reinduction,
      as compared with mice inoculated with irradiated B16 alone, consistent with a
      primarily innate immune mechanism of action of chemo-immunotherapy. In contrast,
      mice deficient in both classical natural killer (NK) lymphocytes and nonclassical
      innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain
      IL2gammac(-/-)) are refractory to chemo-immunotherapy. Classical NK lymphocytes
      are not critical for treatment, as depletion of NK1.1+ cells does not impair
      antitumor effect. Depletion of CD90+NK1.1- lymphocytes, however, both diminishes
      therapeutic benefit and decreases accumulation of macrophages within the tumor.
      Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies
      against native antigen is mediated by the innate immune system. We highlight a
      novel potential role for CD90+NK1.1- ILCs in chemo-immunotherapy.

PMID- 25600444
TI  - A single dose of misoprostol for reducing hemorrhage during myomectomy: a
      randomized clinical trial.
AB  - PURPOSE: To evaluate the effect of vaginal misoprostol on intraoperative bleeding
      during myomectomy. METHOD: In this randomized clinical trial, 80 women with
      myomas were randomly assigned to receive 200 ug misoprostol or placebo (vitamin
      B6) 3 h before surgery. Blood loss during surgery, postoperative need for blood
      transfusion, and the hemoglobin level before surgery, and 6 and 12 h after
      surgery were assessed in two groups. RESULTS: Mean age and the mean preoperative
      and postoperative Hb levels were not significantly different between the two
      groups. Mean duration of surgery and mean estimated blood loss were significantly
      higher in control group. Nine (22.5 %) patients in control group needed blood
      transfusion while there was no need blood transfusion in misoprostol group (p =
      0.001). CONCLUSION: A single dose of vaginal misoprostol is effective in reducing
      hemorrhage during myomectomy.

PMID- 25600442
TI  - Vaginal type-II mucosa is an inductive site for primary CD8+ T-cell mucosal
      immunity.
AB  - The structured lymphoid tissues are considered the only inductive sites where
      primary T-cell immune responses occur. The naive T cells in structured lymphoid
      tissues, once being primed by antigen-bearing dendritic cells, differentiate into
      memory T cells and traffic back to the mucosal sites through the bloodstream.
      Contrary to this belief, here we show that the vaginal type-II mucosa itself,
      despite the lack of structured lymphoid tissues, can act as an inductive site
      during primary CD8(+) T-cell immune responses. We provide evidence that the
      vaginal mucosa supports both the local immune priming of naive CD8(+) T cells and
      the local expansion of antigen-specific CD8(+) T cells, thereby demonstrating a
      different paradigm for primary mucosal T-cell immune induction. 

PMID- 25600443
TI  - Simultaneous quadruple carcinoma of colon Case report and literature review.
AB  - INTRODUCTION: Multiple primary malignancies can arise in the large bowel as
      simultaneous, synchronous and/or metachronous. All tumors must be distant from
      each other to be considered as primitive, none have to be the result of
      metastasis from other tumors. CASE REPORT: We present a case of a 71 years old
      woman who was admitted to our hospital for a 3-year history of not well defined
      abdominal pain and hematochezia. The patient had no family history of cancer.
      Colonoscopy revealed 4 simultaneous tumors located at 4 and 20 cm from the
      ileocecal valve and at 23,2 and 19 cm from the anal verge. At CT scan there were
      no distant metastases, neither lymphonode node involvement. A quadruple
      adenocarcinoma of the colon was confirmed by the pathologist. Patient was
      operated on total colectomy with ileo-rectal anastomosis. DISCUSSION: Two or
      three synchronous tumors of the colon have been already described in literature
      in about 1,8-14% of cases, but the presence of four simultaneous cancers, as in
      our case, is very interesting and unusual without an history of FAP or familiar
      cancer. CONCLUSION: Comprehensive preoperative study, extensive intraoperative
      exploration, and radical resection can improve surgical results and survival
      rate, remaining unquestioned the cause.

PMID- 25600445
TI  - Depression as a risk factor for acute coronary syndrome: a review.
AB  - PURPOSE: In the past few years more and more research focused on psychosocial
      risk factors of cardiovascular disease, including depression. This review focuses
      on depression as a long-term risk factor for acute coronary syndrome in initially
      heart disease-free people. METHODS: The studies included (n = 15) comprised
      people without heart disease who were exposed to depression. The outcome was
      acute coronary syndrome (acute myocardial infarction, instable angina pectoris,
      sudden cardiac death). Only articles published in English between 2000 and 2013
      were considered. RESULTS: Most but not all studies found an association between
      depression and cardiac outcome. Possible explanations for the inconsistency of
      the findings are discussed. CONCLUSIONS: Most likely there is an association
      between depression and acute coronary syndrome. However, it remains unclear
      whether depression acts as an independent risk factor for developing an acute
      coronary syndrome, or if depression promotes the development of an acute coronary
      syndrome by indirect means.

PMID- 25600446
TI  - The clinical problem of colposcopy is represented by false-negatives.

PMID- 25600447
TI  - Modified preoperative computed tomographic-guided localization of colorectal
      liver metastases with metallic clips--technical note.

PMID- 25600448
TI  - Disseminated intravascular coagulation and immune hemolytic anemia, possibly
      Evans syndrome, after oxaliplatin and bevacizumab infusion for metastatic colon
      adenocarcinoma: a case report and literature review.

PMID- 25600449
TI  - Alkaline conditions in hydrophilic interaction liquid chromatography for
      intracellular metabolite quantification using tandem mass spectrometry.
AB  - Modeling of metabolic networks as part of systems metabolic engineering requires
      reliable quantitative experimental data of intracellular concentrations. The
      hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass
      spectrometry (HILIC-ESI-MS/MS) method was used for quantitative profiling of more
      than 50 hydrophilic key metabolites of cellular metabolism. Without prior
      derivatization, sugar phosphates, organic acids, nucleotides, and amino acids
      were measured under alkaline and acidic mobile phase conditions with pre
      optimized multiple reaction monitoring (MRM) transitions. Irrespective of the
      polarity mode of the acquisition method used, alkaline conditions achieved the
      best quantification limits and linear dynamic ranges. Fully 90% of the analyzed
      metabolites presented detection limits better than 0.5pmol (on column), and 70%
      presented 1.5-fold higher signal intensities under alkaline mobile phase
      conditions. The quality of the method was further demonstrated by absolute
      quantification of selected metabolites in intracellular extracts of Escherichia
      coli. In addition, quantification bias caused by matrix effects was investigated
      by comparison of calibration strategies: standard-based external calibration,
      isotope dilution, and standard addition with internal standards. Here, we
      recommend the use of alkaline mobile phase with polymer-based zwitterionic
      hydrophilic interaction chromatography (ZIC-pHILIC) as the most sensitive
      scenario for absolute quantification for a broad range of metabolites. 

PMID- 25600450
TI  - Increased workload for systematic review literature searches of diagnostic tests
      compared with treatments: challenges and opportunities.
AB  - BACKGROUND: Comprehensive literature searches are conducted over multiple medical
      databases in order to meet stringent quality standards for systematic reviews.
      These searches are often very laborious, with authors often manually screening
      thousands of articles. Information retrieval (IR) techniques have proven
      increasingly effective in improving the efficiency of this process. IR challenges
      for systematic reviews involve building classifiers using training data with very
      high class-imbalance, and meeting the requirement for near perfect recall on
      relevant studies. Traditionally, most systematic reviews have focused on
      questions relating to treatment. The last decade has seen a large increase in the
      number of systematic reviews of diagnostic test accuracy (DTA). OBJECTIVE: We aim
      to demonstrate that DTA reviews comprise an especially challenging subclass of
      systematic reviews with respect to the workload required for literature
      screening. We identify specific challenges for the application of IR to
      literature screening for DTA reviews, and identify potential directions for
      future research. METHODS: We hypothesize that IR for DTA reviews face three
      additional challenges, compared to systematic reviews of treatments. These
      include an increased class-imbalance, a broader definition of the target class,
      and relative inadequacy of available metadata (ie, medical subject headings
      (MeSH) terms for medical literature analysis and retrieval system online).
      Assuming these hypotheses to be true, we identify five manifestations when we
      compare literature searches of DTA versus treatment. These manifestations
      include: an increase in the average number of articles screened, and increase in
      the average number of full-text articles obtained, a decrease in the number of
      included studies as a percentage of full-text articles screened, a decrease in
      the number of included studies as a percentage of all articles screened, and a
      decrease in the number of full-text articles obtained as a percentage of all
      articles screened. As of July 12 2013, 13 published Cochrane DTA reviews were
      available and all were included. For each DTA review, we randomly selected 15
      treatment reviews published by the corresponding Cochrane Review Group (N=195).
      We then statistically tested differences in these five hypotheses, for the DTA
      versus treatment reviews. RESULTS: Despite low statistical power caused by the
      small sample size for DTA reviews, strong (P<.01) or very strong (P<.001)
      evidence was obtained to support three of the five expected manifestations, with
      evidence for at least one manifestation of each hypothesis. The observed
      difference in effect sizes are substantial, demonstrating the practical
      difference in reviewer workload. CONCLUSIONS: Reviewer workload (volume of
      citations screened) when screening literature for systematic reviews of DTA is
      especially high. This corresponds to greater rates of class-imbalance when
      training classifiers for automating literature screening for DTA reviews.
      Addressing concerns such as lower quality metadata and effectively modelling the
      broader target class could help to alleviate such challenges, providing possible
      directions for future research.

PMID- 25600451
TI  - Primary radiotherapy for nonsurgically managed Stage I endometrial cancer:
      Utilization and impact of brachytherapy.
AB  - PURPOSE: The National Cancer Data Base (NCDB) was analyzed to evaluate practice
      patterns and the impact of radiotherapy modalities for endometrial cancer treated
      with primary radiotherapy. METHODS AND MATERIALS: The NCDB was queried for Stage
      I endometrioid adenocarcinoma patients treated with primary radiotherapy without
      surgery from 1998 to 2006. Brachytherapy (BT) utilization factors were
      established using multivariable logistic regression. Log-rank and Cox
      proportional hazards modeling were used to assess variables impacting survival.
      RESULTS: A total of 853 patients were analyzed: 23.7%, 31.3%, and 45.0% received
      BT alone, external beam radiotherapy (EBRT) and BT, or EBRT alone. The BT
      utilization ranged from 40.5% to 51.9% over time (p=0.70). Lower utilization was
      associated with advanced age (>=80 years: odds ratio [OR] 0.43, 95% confidence
      interval [CI] 0.28-0.65, p<0.01) and facilities with volume in the bottom
      quartile (OR 0.44, 95% CI 0.30-0.66, p<0.01). Utilization was higher among
      patients living more than 30 miles from the facilities (OR 2.14, 95%CI 1.35-3.42,
      p<0.01). With 36-month median followup, unadjusted median survivals for EBRT dose
      of 30Gy or lower, EBRT dose higher than 30Gy, BT, and EBRT+BT were 12.6, 31.1,
      44.6, and 57.1 months (p<0.01). After correcting for other factors, higher risk
      of mortality was seen with EBRT dose of 30Gy or lower (hazard ratio [HR]2.75, 95%
      CI 1.66-4.55, p<0.01) and EBRT dose higher than 30Gy (HR 1.43, 95% CI 1.07-1.91,
      p=0.02) compared with EBRT+BT. No difference was seen using BT alone (HR 1.29,
      95% CI 0.92-1.79, p=0.14). CONCLUSION: BT utilization for nonsurgically managed
      endometrial cancer remains low with most patients receiving EBRT alone. Despite
      concerns of overtreatment in a population with competing causes of death, BT
      appears to improve survival.

PMID- 25600452
TI  - Update on bacterial pneumonia in the foal and weanling.
AB  - Bacterial pneumonia is a common cause of disease in both neonatal and weanling
      foals. The causal organism or organisms differ with the age of the foal, should
      be identified via microbiologic culture, and will ultimately dictate appropriate
      treatment. Initial treatment in neonates should be broad spectrum and
      bactericidal, whereas weanling age foals may receive more targeted treatment. The
      combination of a macrolide antibiotic and rifampin remains the gold standard for
      treatment of Rhodococcus equi pneumonia; however, resistance to these
      antimicrobials is a concern. 

PMID- 25600453
TI  - Update on bacterial pneumonia and pleuropneumonia in the adult horse.
AB  - Bacterial infections of the lower respiratory tract in adult horses occur when
      bacteria from the nasopharynx reach the lower airways and overwhelm normal
      defense mechanisms. Although Streptococcus equi subsp zooepidemicus is the most
      commonly isolated bacterial species, mixed infections are possible.
      Tracheobronchial aspiration for microbiologic culture and sensitivity is
      suggested in cases presenting with severe clinical signs or not responding to
      treatment. Early intervention and appropriate antimicrobial selection results in
      a good prognosis for both survival and return to athletic function in most
      horses. 

PMID- 25600454
TI  - Update on diseases and treatment of the pharynx.
AB  - This article reviews dorsal displacement of the soft palate (DDSP) and
      nasopharyngeal cicatrix. Palatial instability results in exercise intolerance and
      upper respiratory noise in performance horses. Palatial instability can progress
      to DDSP either permanently or only during exercise. There have been advancements
      related to the etiopathogensis, diagnosis, and treatment of DDSP. The laryngeal
      tie-forward has gained popularity and is the most widely accepted treatment
      option for this condition, either alone or in combination with other procedures.
      Nasopharyngeal cicatrix affects a small geographic region. Diagnosis is
      definitively made via endoscopy. The most effective treatment of this condition
      is a permanent tracheostomy.

PMID- 25600455
TI  - Update on Streptococcus equi subsp equi infections.
AB  - There are few diseases that ignite as much fervor among horse owners as
      strangles. Streptococcus equi subsp equi (strangles) infections frequently
      require the treating veterinarian to manage not only the clinical cases but also
      the biosecurity and provision of information to all involved parties. Although
      the disease is typically characterized by low mortality and high morbidity,
      restrictions of horse movement that result from appropriate quarantine procedures
      often frustrate the involved parties. The aims of this article are to provide
      clinically relevant information for diagnosis, treatment, and biosecurity
      management of strangles infection. 

PMID- 25600456
TI  - [MHC class I antigens, CD4 and CD8 expressions in polymyositis and
      dermatomyositis].
AB  - OBJECTIVE: To analyze the frequencies of the expression of major
      histocompatibility complex class I (MHC-I) antigens, and CD4 and CD8 cells in
      skeletal muscle in polymyositis (PM) and dermatomyositis (DM). METHODS: This was
      a retrospective study of 34 PM cases, 8 DM cases, and 29 control patients with
      non-inflammatory myopathies. RESULTS: MHC-I antigens were expressed in the
      sarcolemma and/or sarcoplasm in 79.4% of PM cases, 62.5% of DM cases, and 27.6%
      of controls (CD4 expression was observed in 76.5%, 75%, and 13.8%, respectively).
      There was a high suspicion of PM/DM (mainly PM) in patients in whom MHC-I
      antigens and CD4 were co-expressed. In 14.3% of PM/DM cases, we observed MHC-I
      antigens expression alone, without inflammatory cells. CONCLUSION: MCH-I antigens
      expression and CD4 positivity might add to strong diagnostic suspicion of PM/DM.
      No cellular infiltration was observed in 14.3% of such cases.

PMID- 25600459
TI  - Negative emotion elicited in high school students enhances consolidation of item
      memory, but not source memory.
AB  - The study examined the effect of negative emotion on consolidation of both item
      and source memory. Participants learned words read by either a male or female.
      Then they watched either a negative or a neutral video clip. Memory tests were
      carried out either 25min or 24h after learning. The study yielded the following
      findings. First, negative emotion enhanced consolidation of item memory as
      measured by recognition memory in the 25-min delay, and enhanced consolidation of
      item memory as measured by free recall in both the 25-min and the 24-h delay.
      Second, negative emotion had little effect on consolidation of source memory,
      either in the 25-min or the 24-h delay. These findings provide evidence for the
      differential effects of negative emotion on item memory and source memory and
      have implications for using emotion as a strategy to intervene memory
      consolidation. 

PMID- 25600460
TI  - Activation of protein kinase C by phorbol ester increases red blood cell
      scramblase activity and external phosphatidylserine.
AB  - Externalization of phosphatidylserine (PS) is thought to contribute to sickle
      cell disease (SCD) pathophysiology. The red blood cell (RBC) aminophospholipid
      translocase (APLT) mediates the transport of PS from the outer to the inner RBC
      membrane leaflet to maintain an asymmetric distribution of PL, while phospholipid
      scramblase (PLSCR) equilibrates PL across the RBC membrane, promoting PS
      externalization. We previously identified an association between PS
      externalization level and PLSCR activity in sickle RBC under basal conditions.
      Other studies showed that activation of protein kinase C (PKC) by PMA (phorbol-12
      myristate-13-acetate) causes increased external PS on RBC. Therefore, we
      hypothesized that PMA-activated PKC stimulates PLSCR activity in RBC and thereby
      contributes to increased PS externalization. In the current studies, we show that
      PMA treatment causes immediate and variable PLSCR activation and subsequent PS
      externalization in control and sickle RBC. While TfR+ sickle reticulocytes
      display some endogenous PLSCR activity, we observed a robust activation of PLSCR
      in sickle reticulocytes treated with PMA. The PKC inhibitor, chelerythrine
      (Chel), significantly inhibited PMA-dependent PLSCR activation and PS
      externalization. Chel also inhibited endogenous PLSCR activity in sickle
      reticulocytes. These data provide evidence that PKC mediates PS externalization
      in RBC through activation of PLSCR. 

PMID- 25600462
TI  - [Nursing practice in maternity intensive care units. Severe pre-eclampsia in a
      primigravida].
AB  - 39 year old woman, pregnant for 31+5 weeks, who came to our intensive care unit
      (ICU) referred from the emergency department of the hospital, having swollen
      ankles, headache and fatigue at moderate effort. We proceeded to take blood
      pressure (158/96 mmHg) and assess lower limb edema. The fetal heart rate
      monitoring was normal. Knowledgeable and user of healthy guidelines during her
      pregnancy, she did not follow any treatment. Single mother, she worried about her
      fetus (achieved through in vitro fertilization), her mother offered to help for
      any mishap. We developed an Individualized Care Plan. For data collection we
      used: Rating 14 Virginia Henderson Needs and diagnostic taxonomy NANDA, NOC, NIC.
      Nursing diagnoses of "fluid volume excess" and "risk of impaired maternal-fetal
      dyad" were detected, as well as potential complications such as eclampsia and
      fetal prematurity. Our overall objectives (NOC) were to integrate the woman in
      the process she faced and that she knew how to recognize the risk factors
      inherent in her illness. Nursing interventions (NIC) contemplated the awareness
      and treatment of her illness and the creation of new healthy habits. The work of
      nursing Maternal ICU allowed women to help maintain maximum maternal and fetal
      well-being by satisfying any of her needs. Mishandling of the situation leads
      into a framework of high morbidity and mortality in our units.

PMID- 25600463
TI  - Cell immobilization for microbial production of 1,3-propanediol.
AB  - Cell and enzyme immobilization are often used for industrial production of high
      value products. In recent years, immobilization techniques have been applied to
      the production of value-added chemicals such as 1,3-Propanediol (1,3-PDO).
      Biotechnological fermentation is an attractive alternative to current 1,3-PDO
      production methods, which are primarily thermochemical processes, as it generates
      high volumetric yields of 1,3-PDO, is a much less energy intensive process, and
      generates lower amounts of environmental organic pollutants. Although several
      approaches including: batch, fed-batch, continuous-feed and two-step continuous
      feed were tested in suspended systems, it has been well demonstrated that cell
      immobilization techniques can significantly enhance 1,3-PDO production and allow
      robust continuous production in smaller bioreactors. This review covers various
      immobilization methods and their application for 1,3-PDO production. 

PMID- 25600461
TI  - [Validation of EMINA and EVARUCI scales for assessing the risk of developing
      pressure ulcers in critical patients].
AB  - OBJECTIVE: To contribute to the validation of the EMINA and EVAUCI scales for
      assessing the risk of pressure ulcers in the critical patient and compare their
      predictive capacity in this same context. METHOD: Prospective study from December
      2012 until June 2013. SETTING: Polyvalent intensive care unit of 14 beds in a
      reference hospital for two sanitary areas. PATIENTS: patients of 18 years of age
      or older and without pressure ulcers were included. They were followed until
      development of a pressure ulcer of grade I or greater, medical discharge, death
      or 30 days. MAIN VARIABLES: presence of ulcers, daily score of the risk of
      developing pressure ulcers through EMINA and EVARUCI evaluation. The validity of
      both scales was calculated using sensitivity, specificity, and positive and
      negative predictive value. The level of significance was P<=0.05. RESULTS: A
      total of 189 patients were evaluated. 67.2% were male with a mean age of 59.4
      (DE: 16,8) years old, 53 (28%) developed pressure ulcers, being the incidence
      rate of 41 ulcers per 1000 admission days. The mean day of diagnosis was 7.7 days
      (DE: 4,4) and the most frequent area was the sacrum. The sensitivity and
      specificity for the mean of observations was 94.34 (IC95% 87.17-100) and 33.33
      (IC95% 25.01-41.66) for the EMINA scale for a risk>10 and 92.45 (IC95% 84.40-100)
      and 42.96 (IC95% 34.24-51.68) for the EVARUCI scale for a risk of>11.
      CONCLUSIONS: No differences were found in predictive capacity of both scales. For
      sensitivities>90%the scales show to be insufficiently specific in the pressure
      ulcer risk detection in critical patients.

PMID- 25600464
TI  - The role of oxidative stress on carotene production by Blakeslea trispora in
      submerged fermentation.
AB  - In aerobic metabolism, reactive oxygen species (ROS) are formed during the
      fermentation that can cause oxidative stress in microorganisms. Microbial cells
      possess both enzymatic and non-enzymatic defensive systems that may protect cells
      from oxidative damage. The antioxidant enzymes superoxide dismutase and catalase
      are the two key defensive enzymes to oxidative stress. The factors that induce
      oxidative stress in microorganisms include butylated hydroxytoluene (BHT),
      hydrogen peroxide, metal ions, dissolved oxygen tension, elevated temperature,
      menadione, junglone, paraquat, liquid paraffin, introduction to bioreactors of
      shake flask inocula and synthetic medium sterilized at initial pH 11.0. Carotenes
      are highly unsaturated isoprene derivatives. They are used as antioxidants and as
      coloring agents for food products. In fungi, carotenes are derived via the
      mevalonate biosynthesis pathway. The key genes in carotene biosynthesis are hmgR,
      ipi, isoA, carG, carRA and carB. Among microorganisms, Betalakeslea trispora is
      the main microorganism used for the production of carotenes on the industrial
      scale. Currently, the synthetic medium is considered the superior substrate for
      the production of carotenes in a pilot plant scale. The fermentation systems used
      for the production of carotenes include shake flasks, stirred tank fermentor,
      bubble column reactor and flat panel photobioreactor. This review summarizes the
      oxidative stresses in microorganisms and it is focused on the current status of
      carotene production by B. trispora including oxidative stress induced by BHT,
      enhanced dissolved oxygen levels, iron ions, liquid paraffin and synthetic medium
      sterilized at an initial pH 11.0. The oxidative stress induced by the above
      factors increases significantly the production of carotenes. However, to further
      reduce the cost of carotene production, new biotechnological methods with higher
      productivity still need to be explored. 

PMID- 25600465
TI  - Targeted localized use of therapeutic antibodies: a review of non-systemic,
      topical and oral applications.
AB  - Therapeutic antibodies provide important tools in the "medicine chest" of today's
      clinician for the treatment of a range of disorders. Typically monoclonal or
      polyclonal antibodies are administered in large doses, either directly or
      indirectly into the circulation, via a systemic route which is well suited for
      disseminated ailments. Diseases confined within a specific localized tissue,
      however, may be treated more effectively and at reduced cost by a delivery system
      which targets directly the affected area. To explore the advantages of the local
      administration of antibodies, we reviewed current alternative, non-systemic
      delivery approaches which are in clinical use, being trialed or developed. These
      less conventional approaches comprise: (a) local injections, (b) topical and (c)
      peroral administration routes. Local delivery includes intra-ocular injections
      into the vitreal humor (i.e. Ranibizumab for age-related macular degeneration),
      subconjunctival injections (e.g. Bevacizumab for corneal neovascularization),
      intra-articular joint injections (i.e. anti-TNF alpha antibody for persistent
      inflammatory monoarthritis) and intratumoral or peritumoral injections (e.g.
      Ipilimumab for cancer). A range of other strategies, such as the local use of
      antibacterial antibodies, are also presented. Local injections of antibodies
      utilize doses which range from 1/10th to 1/100th of the required systemic dose
      therefore reducing both side-effects and treatment costs. In addition, any
      therapeutic antibody escaping from the local site of disease into the systemic
      circulation is immediately diluted within the large blood volume, further
      lowering the potential for unwanted effects. Needle-free topical application
      routes become an option when the condition is restricted locally to an external
      surface. The topical route may potentially be utilized in the form of eye drops
      for infections or corneal neovascularization or be applied to diseased skin for
      psoriasis, dermatitis, pyoderma gangrenosum, antibiotic resistant bacterial
      infections or ulcerated wounds. Diseases confined to the gastrointestinal tract
      can be targeted directly by applying antibody via the injection-free peroral
      route. The gastrointestinal tract is unusual in that its natural immuno-tolerant
      nature ensures the long-term safety of repeatedly ingesting heterologous
      antiserum or antibody materials. Without the stringent regulatory, purity and
      clean room requirements of manufacturing parenteral (injectable) antibodies,
      production costs are minimal, with the potential for more direct low-cost
      targeting of gastrointestinal diseases, especially with those caused by
      problematic antibiotic resistant or toxigenic bacteria (e.g. Clostridium
      difficile, Helicobacter pylori), viruses (e.g. rotavirus, norovirus) or
      inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease). Use of the
      oral route has previously been hindered by excessive antibody digestion within
      the gastrointestinal tract; however, this limitation may be overcome by
      intelligently applying one or more strategies (i.e. decoy proteins, masking
      therapeutic antibody cleavage sites, pH modulation, enzyme inhibition or
      encapsulation). These aspects are additionally discussed in this review and novel
      insights also provided. With the development of new applications via local
      injections, topical and peroral routes, it is envisaged that an extended range of
      ailments will increasingly fall within the clinical scope of therapeutic
      antibodies further expanding this market. 

PMID- 25600466
TI  - Success of a smoking cessation programme in smoking behaviour of chronic
      periodontitis patients and identification of predictors of motivation for smoking
      cessation - a pilot study.
AB  - BACKGROUND: The primary goal of this pilot study was to evaluate the success of a
      smoking cessation programme on smoking behaviour of patients with chronic
      periodontitis. Secondary goals were to identify the prevalence of smoking among
      them, predictors of motivation for smoking cessation and for successful nicotine
      abstinence. METHODS: Smokers suffering from chronic periodontitis were offered
      cognitive behavioural group therapy of 10 once-weekly sessions. Smoking is
      reduced stepwise and complete cessation is to be achieved by the sixth session.
      Sociodemographic data, history of smoking and motivation for smoking cessation,
      subjective health status, and questionnaires on anxiety, depression, control
      beliefs and coping with stress were completed at study entry. Smoking behaviour
      was assessed at the end of the group programme and 3 months thereafter. RESULTS:
      Of 469 patients with periodontitis, 59 (12.6%) were smokers; 30 (50.6%) patients
      participated in the smoking cessation programme. Participants smoked more
      cigarettes/day (P = 0.03, 95% CI: -17.9/-0.89) and subjectively assessed their
      health as being worse than non-participants (P = 0.09, 95% CI: -0.16/2.15). In
      SPQ, non-participants showed more trivialization (P = 0.014, 95% CI: 0.59/4.94).
      Complete data were available for 15 group participants: six patients were smoke
      free after 10 weeks and five after 18 weeks (33.3%); two patients had reduced
      their cigarette consumption by half. At the start of the programme, less
      successful participants showed a tendency to higher depression in HADS (P =
      0.085, 95% CI: -5.25/5.76) and were more inclined to seek substitute satisfaction
      (P = 0.034, 95% CI: 3.24/11.23). CONCLUSION: The rate of success in this study
      was comparable with other studies. More research with larger samples is needed
      for confirming these observations.

PMID- 25600467
TI  - Physiological responses to increased brood size and ectoparasite infestation:
      Adult great tits favour self-maintenance.
AB  - Different types of stressors trigger responses of different physiological
      systems, and these responses may contribute differentially to the maintenance of
      homeostasis, to trade-offs and the evolution of life-history traits. To
      manipulate two common stressors during reproduction, we infested half of the
      nests in a naturally breeding great tit population with ectoparasites and
      simultaneously manipulated brood size, using a 2*2 experimental design. Parents
      in this model species commonly compensate for ectoparasites by an increase in
      food provisioning. We assessed parental responses to these concurrent stressors
      by measuring several physiological stress parameters such as changes in metabolic
      rate, oxidative stress and expression of heat-shock proteins (Hsp), and explored
      how these stressors affect the trade-off between self-maintenance and
      reproduction. Neither flea infestation nor brood size manipulation affected adult
      metabolic rate, oxidative damage or Hsp levels. Furthermore, we found no
      interactive effect of the two treatments on adults. However, nestlings in
      infested nests had lower body mass and lower survival. Nestlings in enlarged
      broods were lighter and had lower survival, although parents of enlarged broods
      increased food provisioning rate. The findings suggest that adults favour
      maintenance of cellular homeostasis, and physiological equilibrium over current
      reproduction, and that the costs induced by both stressors, flea infestation and
      increased brood size, are carried by the offspring. It emphasizes the importance
      of self-maintenance over reproduction in life-history decisions, and more
      generally the need of including physiological traits for understanding the
      evolution of life-histories. 

PMID- 25600469
TI  - Binge eating disorder and obesity: preliminary evidence for distinct
      cardiovascular and psychological phenotypes.
AB  - This study investigated cardiovascular functioning, mood, and eating-related
      psychological factors at rest and in response to mental stress in three groups of
      women: 1) Obese women with binge eating disorder (BED; n=9); 2) obese non-BED
      women (n=15); and 3) normal weight (NW) non-BED women (n=15). Compared to both
      obese and NW non-BED women, obese women with BED showed heightened overall blood
      pressure and reported greater depression symptoms, perceived stress, and eating
      related psychopathology. Additionally, obese women with BED reported greater
      overall negative affect and state anxiety compared to obese non-BED women. The
      heart rate response to stress was blunted in the obese BED group compared to the
      other groups, but this effect was no longer significant after controlling for
      baseline differences in depression. Correlational analyses revealed a positive
      association between stress-induced changes in hunger and cardiovascular measures
      only in obese women with BED. Longitudinal studies are needed to determine if
      stress dysregulation and stress-induced increases in hunger contribute to the
      onset and/or maintenance of BED. In particular, studies utilizing an additional
      NW BED control group are warranted in order to further examine the impact of BED
      above and beyond the impact of obesity on psychophysiological functioning and to
      inform the growing literature regarding stress-related factors that distinguish
      the BED and obesity phenotypes. 

PMID- 25600468
TI  - Prenatal alcohol exposure selectively enhances young adult perceived pleasantness
      of alcohol odors.
AB  - Prenatal alcohol exposure (PAE) can lead to life-long neurobehavioral and social
      problems that can include a greater likelihood of early use and/or abuse of
      alcohol compared to older teens and young adults without PAE. Basic research in
      animals demonstrates that PAE influences later postnatal responses to
      chemosensory cues (i.e., odor & taste) associated with alcohol. We hypothesized
      that PAE would be related to poorer abilities to identify odors of alcohol
      containing beverages, and would alter perceived alcohol odor intensity and
      pleasantness. To address this hypothesis we examined responses to alcohol and
      other odors in a small sample of young adults with detailed prenatal histories of
      exposure to alcohol and other drugs. The key finding from our controlled analyses
      is that higher levels of PAE were related to higher relative ratings of
      pleasantness for alcohol odors. As far as we are aware, this is the first
      published study to report the influence of PAE on responses to alcohol beverage
      odors in young adults. These findings are consistent with the hypothesis that
      positive associations (i.e., "pleasantness") to the chemosensory properties of
      alcohol (i.e., odor) are acquired prenatally and are retained for many years
      despite myriad interceding postnatal experiences. Alternate hypotheses may also
      be supported by the results. There are potential implications of altered alcohol
      odor responses for understanding individual differences in initiation of
      drinking, and alcohol seeking and high-risk alcohol-related behaviors in young
      adults. 

PMID- 25600470
TI  - A systematic review of quality and cost-effectiveness derived from Markov models
      evaluating smoking cessation interventions in patients with chronic obstructive
      pulmonary disease.
AB  - Smoking cessation is the only strategy that has shown a lasting reduction in the
      decline of lung function in patients with chronic obstructive pulmonary disease.
      This study aims to evaluate the cost-effectiveness of smoking cessation
      interventions in patients with chronic obstructive pulmonary disease, to assess
      the quality of the Markov models and to estimate the consequences of model
      structure and input data on cost-effectiveness. A systematic literature search
      was conducted in PubMed, Embase, BusinessSourceComplete and Econlit on June 11,
      2014. Data were extracted, and costs were inflated. Model quality was evaluated
      by a quality appraisal, and results were interpreted. Ten studies met the
      inclusion criteria. The results varied widely from cost savings to additional
      costs of ?17,004 per quality adjusted life year. The models scored best in the
      category structure, followed by data and consistency. The quality of the models
      seems to rise over time, and regarding the results there is no economic reason to
      refuse the reimbursement of any smoking cessation intervention. 

PMID- 25600471
TI  - Interaction of model aryl- and alkyl-boronic acids and 1,2-diols in aqueous
      solution.
AB  - The goal of this work was to quantitate ester formation between alkyl and aryl
      boronic acids and vicinal-diols or 1,2-diols in aqueous solution. As used here,
      1,2-diols includes polyols with one or more 1,2-diol pairs. Multiple techniques
      were used including apparent pKa shifts of the boronic acids using UV
      spectrophotometry (for aryl acids) and titration (for aryl and alkyl acids).
      Isothermal microcalorimetry was also used, with all reactions being enthalpically
      favored. For all the acids and 1,2-diols and the conditions studied, evidence
      only supported 1:1 ester formation. All the esters formed were found to be
      significantly more acidic, as Lewis acids, by 3-3.5 pKa units than the
      corresponding nonesterified boronic acid. The equilibrium constants for ester
      formation increased with increasing number of 1,2-diol pairs but stereochemistry
      may also play a role as sorbitol with five possible 1,2-diol pairs and five
      isomers (taking into account the stereochemistry of the alcohol groups) was twice
      as efficient at ester formation compared with mannitol, also with five possible
      1,2-diol pairs but only three isomers. Alkyl boronic acids formed esters to a
      greater extent than aryl acids. Although some quantitative differences were seen
      between the various techniques used, rank ordering of the structure/reactivity
      was consistent. Formulation implications of ester formation between boronic acids
      and 1,2-diols are discussed.

PMID- 25600472
TI  - Randomized, double-blind, controlled, comparative study on intralesional 10% and
      15% hypertonic saline versus intralesional sodium stibogluconate in Leishmania
      donovani cutaneous leishmaniasis.
AB  - BACKGROUND: Intralesional 7% hypertonic saline (HS) has been shown to be
      effective and safe against Leishmania donovani and Leishmania major cutaneous
      leishmaniasis (CL), with cure rates of 92% and 96%, respectively. This study was
      designed to assess the efficacy and safety of 10% and 15% HS in CL. METHODS: A
      total of 444 patients (643 lesions) were randomly allocated to sodium
      stibogluconate (SSG), 10% HS and 15% HS at a ratio of 2 : 2 : 1, taking into
      consideration any unwanted side effects that might arise with 15% HS. The follow
      up period was 18 months. Survival analysis using Cox proportional hazard
      regression was performed to assess the effectiveness of the three treatment
      modalities. The clinical trial was registered at the Sri Lanka Clinical Trial
      Registry (SLCTR/2013/024). RESULTS: Treatment with SSG resulted in a cure rate of
      96.3% within one to seven injections (mean: 3.6 injections); the mean (median)
      duration of treatment was six weeks (6 weeks) per lesion. Treatment with 10% HS
      showed a cure rate of 93.0% within one to 10 injections (mean: 5.28 injections);
      the mean (median) duration of treatment was 9.3 weeks (9 weeks) per lesion.
      Treatment with 15% HS showed a cure rate of 93.6% within two to 10 injections
      (mean: 5.3 injections); the mean (median) duration of treatment was 11.3 weeks
      (10.0 weeks) per lesion. Treatment with 10% HS and 15% HS caused cutaneous
      necrosis in 3.1% and 30.6% of lesions, respectively. Despite continuous data
      collection for 14 months, we were unable to recruit a sample of sufficient size.
      Seventeen (3.8%) patients were lost to follow-up, and 24 (5.4%) were partial or
      non-responders. CONCLUSIONS: This study found 10% HS to be an effective and safe
      alternative to SSG. Treatment with HS at concentrations of 15% or above was not
      safe as a result of cutaneous necrosis. Safety was not studied for concentrations
      of 11-14%, and these concentrations should be avoided pending further evidence.
      Hypertonic saline is very cheap (< US$1 per 100 ml, whereas SSG is priced at
      US$160 per 100 ml), is prepared locally and has no systemic side effects and
      minimal local side effects.

PMID- 25600473
TI  - Accelerated bone loss and increased post-fracture mortality in elderly women and
      men.
AB  - Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We
      found accelerated bone loss (>=1.31 % bone loss/year for women and >=1.35 % bone
      loss/year for men) associated with 44-77 % increased mortality. It remains
      unclear whether bone loss is a marker or plays a role in mortality. INTRODUCTION:
      Osteoporotic fractures are associated with increased mortality although the cause
      is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated
      with increased mortality, but its role in mortality risk post-fracture is
      unclear. This study aimed to examine post-fracture mortality risk according to
      levels of bone loss. METHODS: Community-dwelling participants aged 60+ from Dubbo
      Osteoporosis Epidemiology Study with incident fractures were followed from 1989
      to 2011. Kaplan-Meier survival curves were constructed according to bone loss
      quartiles. Cox proportional hazard models were used to determine the effect of
      bone loss on mortality. RESULTS: There were 341 women and 106 men with >=2 BMD
      measurements. The rate of bone loss was similar for women and men (women mean 
      0.79 %/year, highest bone loss quartile -1.31 %/year; men mean -0.74 %/year,
      highest quartile -1.35 %/year). Survival was lowest for the highest quartile of
      bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture
      type, the association of bone loss with mortality was observed for vertebral
      (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and
      non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an
      additional role in mortality risk following hip fractures. Importantly, overall,
      rapid bone loss was associated with 44-77 % increased mortality risk after
      multiple variable adjustment. CONCLUSION: Rapid bone loss was an independent
      predictor of post-fracture mortality risk in both women and men. The association
      of bone loss and post-fracture mortality was predominantly observed following
      vertebral fracture in both women and men and non-hip non-vertebral fracture in
      women. It remains to be determined whether bone loss is a marker or plays a role
      in the mortality associated with fractures.

PMID- 25600474
TI  - Fracture rate associated with quality metric-based anti-osteoporosis treatment in
      glucocorticoid-induced osteoporosis.
AB  - Anti-osteoporosis medication (AOM) use in patients exposed to glucocorticoids is
      thought to reduce fractures. We found post-menopausal women using glucocorticoids
      for at least 90 days who also used an AOM within 90 days had 48 % fewer fractures
      by 1 year and 32 % fewer fractures by 3 years compared to non-AOM users.
      INTRODUCTION: The purpose of this study is to explore the effectiveness of
      adherence to quality measures by estimating the effect of anti-osteoporosis
      medication (AOM) initiation within 90 days after chronic (>=90 days)
      glucocorticoid (GC) therapy on osteoporotic fracture. METHODS: A new-user cohort
      was assembled using the MarketScan databases between 2000 and 2012. Included
      patients were female, age >=50 at GC initiation, had a first GC fill daily dose
      >=10 mg and persisted for at least 90 days. During a 365-day baseline period,
      patients were excluded for prior GC or AOM (bisphosphonate, denosumab,
      teriparatide) use, fracture, or cancer diagnosis. Initiators of an AOM in the 14
      days pre- or 90 days post-GC fill were characterized as AOM users; those without,
      AOM non-users. Follow-up began 91 days after GC fill with patients followed until
      fracture, loss of continuous enrollment, initiation of AOM by AOM non-users, or
      end of study period. A propensity score was estimated for AOM receipt using all
      measured covariates and converted to a stabilized inverse probability of
      treatment weights (IPTW). Weighted hazard ratios (HR) and associated 95%
      confidence intervals (95% CI) were estimated using weighted Cox proportional
      hazard models. RESULTS: Of the 7885 women eligible for the study, 12.1% were AOM
      users. AOM use was associated with lower fracture incidence: weighted HR of 0.52
      (95% CI 0.29, 0.94) at 1 year and weighted HR of 0.68 (95% CI 0.47, 0.99) at 3
      years. CONCLUSIONS: AOM initiation within 90 days of chronic GC use was
      associated with a fracture reduction of 48% at 1 year and 32% at 3 years.

PMID- 25600476
TI  - The impact of arthritis on the early employment experiences of young adults: A
      literature review.
AB  - BACKGROUND: Young adulthood is an important transitional life phase that can
      determine a person's career trajectory. To date, little research has examined the
      influence of arthritis on early work experiences. OBJECTIVES: This literature
      review aims at examining the impact of arthritis on the early career phase of
      young adults and identifying the barriers to employment. METHODS: Two independent
      reviewers searched bibliographic databases for arthritis conditions and a series
      of employment-related keywords and subject headings. Information on authors,
      publication year; study design, sample characteristics (e.g., number of
      participants, age, gender, arthritis type); work outcomes measured; and specific
      barriers to employment was recorded. RESULTS: Nine studies were uncovered in the
      review. All studies examined young people with juvenile arthritis (9 of 9
      studies) and consisted of sample sizes with less then 150 participants (6 of 9
      studies) who were primarily recruited from clinics (7 of 9 studies). All were
      cross-sectional designs. Employment status was primarily examined and ranged from
      11% to 71%. Although not always statistically significant, young adults with
      arthritis were less likely to be employed when compared to their healthy peers.
      Greater disease severity, less educational attainment and being female were
      related to not participating in paid work. CONCLUSION: This review brings to
      light the paucity of studies examining the early employment experiences of young
      adults with arthritis. There is a need to expand research to contribute to
      recommendations for sustained and productive employment across the working life
      course.

PMID- 25600475
TI  - Persistent hypovitaminosis D and loss of hip bone mineral density over time as
      additional risk factors for recurrent falls in a population-based prospective
      cohort of elderly persons living in the community. The Sao Paulo Ageing & Health
      (SPAH) Study.
AB  - We performed concomitant evaluation of clinical, laboratory, and bone mineral
      density (BMD) parameters as potential risk factors for falls in a population
      based prospective cohort of older adults, since previous studies have focused
      mostly in clinical risk factors. Loss of hip BMD and persistent hypovitaminosis D
      were associated with recurrent falls in community-dwelling elderly. INTRODUCTION:
      Few studies have performed a concomitant evaluation of clinical data, laboratory
      bone parameters, and bone mineral density (BMD) to determine more accurately the
      contribution of each of these variables to risk of falls in elderly persons. We
      investigated the association between bone parameters and recurrent falls in a
      population-based prospective cohort of community-dwelling older adults. METHODS:
      A total of 705 elderly individuals (448 women, 257 men) were evaluated with
      clinical data, BMD, and laboratory bone tests at baseline and after a mean follow
      up of 4.3 +/- 0.8 years. Individuals with recurrent falls (>=2 falls in the
      previous year from the date of the second evaluation) were considered chronic
      fallers. Logistic regression models were used to identify independent risk
      factors for recurrent falls. RESULTS: The frequency of chronic fallers was 16.5%.
      In multivariate analyses, risk factors for recurrent falls were visual impairment
      (odds ratio (OR) = 2.49, 95% confidence interval (CI) 1.30-4.74, p = 0.006), use
      of psychotropic drugs (OR = 2.47, 95% CI 1.37-4.49, p = 0.003), clinical fracture
      (OR = 2.78, 95% CI 1.48-5.20, p = 0.001), persistently low 25-hydroxyvitamin D
      (25OHD) (<20 ng/mL) (OR = 1.71, 95% CI 1.10-2.64, p = 0.016), and loss of total
      hip BMD during the study (OR = 1.21, 95% CI 1.17-1.25, p = 0.035 for each 4%
      decrease). CONCLUSIONS: In addition to traditional clinical risk factors for
      falls, loss of hip BMD and hypovitaminosis D were associated with recurrent falls
      in community-dwelling elderly persons. Thus, recognizing these factors is
      essential to preventing falls and improving the outcomes of this population.

PMID- 25600478
TI  - Non-alcoholic fatty liver disease: today and tomorrow.

PMID- 25600477
TI  - Total synthesis of periploside A, a unique pregnane hexasaccharide with potent
      immunosuppressive effects.
AB  - Periploside A is a pregnane hexasaccharide identified from the Chinese medicinal
      plant Periploca sepium, which features a unique seven-membered formyl acetal
      bridged orthoester (FABO) motif and potent immunosuppressive activities. Here, we
      show the synthesis of this molecule in a total of 76 steps with the longest
      linear sequence of 29 steps and 9.2% overall yield. The FABO motif is constructed
      via a combination of Sinay's and Crich's protocol for the formation of orthoester
      and acetal glycosides, respectively. The 2-deoxy-beta-glycosidic linkages are
      assembled stereoselectively with judicious choice of the glycosylation methods.
      The epimer at the spiro-quaternary carbon in the FABO motif has also been
      elaborated in a stereo-controlled manner. This epimer, as well as the synthetic
      analogues bearing the FABO motif, retain largely the inhibitory activities of
      periploside A against the proliferation of T-lymphocyte, indicating the
      importance of the chemical connection of the FABO motif to their
      immunosuppressive activity. 

PMID- 25600479
TI  - A case of cutaneous vegetating candidiasis in a patient with Keratitis-Ichthyosis
      Deafness Syndrome.

PMID- 25600480
TI  - How is FLC repression initiated by cold?
AB  - Vernalization is the promotion of flowering in response to prolonged exposure to
      low temperatures. In Arabidopsis, FLOWERING LOCUS C (FLC), a suppressor of
      flowering, is repressed by low temperatures but the mechanism leading to the
      initial decrease in FLC transcription remains a mystery. No mutants that block
      the repression of FLC at low temperatures have been identified to date. If the
      failure to identify such a mutant is assumed to imply that no such mutant exists,
      then it follows that the first response to the drop in temperature is physical,
      not genetic. In this Opinion article we propose that the drop in temperature
      first causes a simple change in the topology of the chromatin polymer, which in
      turn initiates the repression of FLC transcription. 

PMID- 25600481
TI  - Hirayama disease: the importance of an early diagnosis.

PMID- 25600482
TI  - Resting-state frontostriatal functional connectivity in Parkinson's disease
      related apathy.
AB  - One of the most common neuropsychiatric symptoms in Parkinson's disease (PD) is
      apathy, affecting between 23% and 70% of patients and thought to be related to
      frontostriatal dopamine deficits. In the current study, we assessed functional
      resting-state frontostriatal connectivity and structural changes associated with
      the presence of apathy in a large sample of PD subjects and healthy controls,
      while controlling for the presence of comorbid depression and cognitive decline.
      Thirty-one healthy controls (HC) and 62 age-, sex-, and education-matched PD
      patients underwent resting-state functional magnetic resonance imaging (MRI).
      Apathy symptoms were evaluated with the Apathy Scale (AS). The 11 Beck Depression
      Inventory-II items that measure dysphoric mood symptoms as well as relevant
      neuropsychological scores were used as nuisance factors in connectivity analyses.
      Voxel-wise analyses of functional connectivity between frontal lobes (limbic,
      executive, rostral motor, and caudal motor regions), striata (limbic, executive,
      sensorimotor regions), and thalami were performed. Subcortical volumetry/shape
      analysis and fronto-subcortical voxel-based morphometry were performed to assess
      associated structural changes. Twenty-five PD patients were classified as
      apathetic (AS > 13). Apathetic PD patients showed functional connectivity
      reductions compared with HC and with non-apathetic patients, mainly in left-sided
      circuits, and predominantly involving limbic striatal and frontal territories.
      Similarly, severity of apathy negatively correlated with connectivity in these
      circuits. No significant effects were found in structural analyses. Our results
      indicate that the presence of apathy in PD is associated with functional
      connectivity reductions in frontostriatal circuits, predominating in the left
      hemisphere and mainly involving its limbic components.

PMID- 25600483
TI  - Thyroid nodules <= 5 mm on ultrasonography: are they "leave me alone" lesions?
AB  - The incidence of small thyroid malignancy has increased. However, there is no
      evidence-based guideline for managing thyroid nodules <= 5 mm on ultrasonography
      (US). We evaluated how to manage thyroid nodules <= 5 mm. Thyroid nodules <= 5 mm
      in size on US that had undergone surgery and US-guided fine-needle aspiration
      were eligible. A total of 3,117 thyroid nodules in 3,012 patients were included.
      The size changes of malignant and benign nodules during follow-up were evaluated.
      Thyroid malignancies were classified according to follow-up and surgery time
      within and after 12 months. Clinico-pathological characteristics were compared.
      Of 3,117 nodules, 1,639 nodules in 1,619 patients were benign and 1,478 in 1,427
      were malignant. Only 5.8 and 1.2 % of malignant nodules and 6.8 and 4.2 % of
      benign nodules increased in size when a 2-mm and 3-mm change on US were
      referenced. Of 1,079 patients with an index malignancy <= 5 mm, extrathyroidal
      extension, lymph node metastasis, recurrence, and mortality were not
      significantly different between patients with and without follow-up and between
      patients with surgery within 12 months and after 12 months. None of the patients
      who underwent surgery had distant metastasis and none died of thyroid malignancy.
      In thyroid nodules <= 5 mm found on US, US-FNA could be recommended in cases of
      increased size during US follow-up if lateral LNM was not found because a delay
      in surgery did not impact cancer recurrence and mortality.

PMID- 25600485
TI  - mer and fac isomerism in tris chelate diimine metal complexes.
AB  - In this perspective, we highlight the issue of meridional (mer) and facial (fac)
      orientation of asymmetrical diimines in tris-chelate transition metal complexes.
      Diimine ligands have long been the workhorse of coordination chemistry, and
      whilst there are now good strategies to isolate materials where the inherent
      metal centered chirality is under almost complete control, and systematic
      methodologies to isolate heteroleptic complexes, the conceptually simple
      geometrical isomerism has not been widely investigated. In systems where the two
      donor atoms are significantly different in terms of the sigma-donor and pi
      accepting ability, the fac isomer is likely to be the thermodynamic product. For
      the diimine complexes with two trigonal planar nitrogen atoms there is much more
      subtlety to the system, and external factors such as the solvent, lattice packing
      and the various steric considerations play a delicate role in determining the
      observed and isolable product. In this article we discuss the possibilities to
      control the isomeric ratio in labile systems, consider the opportunities to
      separate inert complexes and discuss the observed differences in their
      spectroscopic properties. Finally we report on the ligand orientation in
      supramolecular systems where facial coordination leads to simple regular
      structures such as helicates and tetrahedra, but the ability of the ligand system
      to adopt a mer orientation enables self-assembled structures of considerable
      beauty and complexity. 

PMID- 25600484
TI  - Effect of 1-year dietary supplementation with vitaminized olive oil on markers of
      bone turnover and oxidative stress in healthy post-menopausal women.
AB  - Osteoporosis represents a serious health problem worldwide associated with an
      increased risk of fractures and mortality. Nutrition should form part of bone
      disease prevention strategies, especially in the light of the population ageing
      and the diet effect on bone health. Thus the study aimed at verifying whether 1
      year of oral supplementation with either extra virgin olive oil (VOO) enriched
      with vitamins D3, K1 and B6 (VitVOO) or VOO used as placebo (PlaVOO) is able to
      modify some bone turnover and oxidative stress markers. Bone mineral density
      (BMD) was assessed in 60 healthy post-menopausal women together with the bone
      vitamin K status by measuring undercarboxylated osteocalcine (ucOC) plasma
      levels, the ratio between ucOC and carboxylated osteocalcine (UCR) and the
      relations with oxidative stress markers. After 1 year (T 1), subjects taking
      VitVOO showed lower ucOC levels than those taking PlaVOO; the same trend was
      found for UCR. As far as BMD is concerned, a significant increase in T-score at T
      1 in VitVOO subjects compared to PlaVOO was found. All oxidative stress markers
      as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated
      dienes showed a significant reduction after VitVOO supplementation, whilst plasma
      total antioxidant capacity values was significantly increased in VitVOO group
      compared to PlaVOO group at T 1. It might be suggested that the use of VitVOO in
      the diet of post-menopausal women could represent a proper tool for bone
      protection and a useful strategy against oxidative stress and related diseases,
      thus confirming the antioxidant role played by the added vitamins. 

PMID- 25600486
TI  - The histone chaperone complex HIR maintains nucleosome occupancy and
      counterbalances impaired histone deposition in CAF-1 complex mutants.
AB  - Chromatin organization is essential for coordinated gene expression, genome
      stability, and inheritance of epigenetic information. The main components
      involved in chromatin assembly are specific complexes such as Chromatin Assembly
      Factor 1 (CAF-1) and Histone Regulator (HIR), which deposit histones in a DNA
      synthesis-dependent or -independent manner, respectively. Here, we characterize
      the role of the plant orthologs Histone Regulator A (HIRA), Ubinuclein (UBN) and
      Calcineurin Binding protein 1 (CABIN1), which constitute the HIR complex.
      Arabidopsis loss-of-function mutants for the various subunits of the complex are
      viable, but hira mutants show reduced fertility. We show that loss of HIRA
      reduces extractable histone H3 protein levels and decreases nucleosome occupancy
      at both actively transcribed genes and heterochromatic regions. Concomitantly,
      HIRA contributes to maintenance of silencing of pericentromeric repeats and
      certain transposons. A genetic analysis based on crosses between mutants
      deficient in subunits of the CAF-1 and HIR complexes showed that simultaneous
      loss of both the CAF-1 and HIR histone H3 chaperone complexes severely affects
      plant survival, growth and reproductive development. Our results suggest that
      HIRA partially rescues impaired histone deposition in fas mutants to preserve
      nucleosome occupancy, implying plasticity in histone variant interaction and
      deposition. 

PMID- 25600487
TI  - Fifty years of dialysis in Africa: challenges and progress.
AB  - This review addresses the development of dialysis services in Africa in the face
      of past and contemporary challenges. Maintenance dialysis treatment programs
      developed in 29 countries over the past 50 years, usually many years after their
      independence and the end of subsequent territorial and civil wars. Eight
      countries had the resources to launch national dialysis programs, conventionally
      defined as those accommodating at least 100 patients per million population.
      Additionally, based on information obtained from international and local
      publications, conference proceedings, and personal communications, it appears
      that limited short-term dialysis therapy currently is available in most African
      countries. Currently, the prevalence of and outcomes associated with dialysis in
      Africa are influenced significantly by the following: (1) local health indexes,
      including the prevalence of undernutrition and chronic infections; (2) per capita
      gross domestic product; (3) national expenditures on health and growth of these
      expenditures with incremental demand; (4) availability and adequate training of
      health care providers; and (5) literacy. In an attempt to reduce the
      socioeconomic burden of maintenance dialysis treatment, 12 countries have adopted
      active transplantation programs and 5 are striving to develop screening and
      prevention programs. Our recommendations based on these observations include
      optimizing dialysis treatment initiatives and integrating them with other health
      strategies, as well as training and motivating local health care providers. These
      steps should be taken in collaboration with regulatory authorities and the
      public. 

PMID- 25600489
TI  - Brincidofovir for polyomavirus-associated nephropathy after allogeneic
      hematopoietic stem cell transplantation.
AB  - Polyomavirus-associated nephropathy (PVAN) is common in patients who have
      undergone kidney transplantation and has been reported in hematopoietic stem cell
      (HSC) transplant recipients. Aside from reduction of immunosuppression, few
      therapeutic options exist for treatment of PVAN. We report a case of PVAN in a
      severely immunocompromised allogeneic HSC transplant recipient that was treated
      with brincidofovir without reduction of immunosuppression. We review our
      institutional experience of PVAN in HSC transplantation and discuss the potential
      use of brincidofovir for treatment.

PMID- 25600488
TI  - Parental history of premature cardiovascular disease, estimated GFR, and rate of
      estimated GFR decline: results from the Aerobics Center Longitudinal Study.
AB  - BACKGROUND: Despite cardiovascular disease (CVD) and chronic kidney disease
      sharing similar causes and interplay, it is unknown if a broader relationship
      between these diseases exists across generations. We investigated the association
      between parental CVD history and estimated glomerular filtration rate (eGFR) in
      the community. STUDY DESIGN: Cross-sectional and longitudinal analyses. SETTING &
      PARTICIPANTS: 13,241 community-based adults with serum creatinine measurement and
      follow-up visits (from 1-8 visits ~2 years apart) from the Aerobics Center
      Longitudinal Study. PREDICTORS: Premature parental CVD history (before age 50
      years). OUTCOMES: eGFR, decreased eGFR (<60 mL/min/1.73 m(2)), and rate of eGFR
      decline. MEASUREMENTS: Information for parental history was collected by protocol
      standardized questionnaires. eGFR was assessed with serum creatinine. RESULTS:
      3,339 (25.2%) participants reported a history of parental CVD. Individuals with
      parental CVD had significantly lower eGFRs compared with those without parental
      CVD (69.4 +/- 12.9 vs 74.8 +/- 14.2 mL/min/1.73 m(2); P<0.001). After
      multivariable adjustment, parental CVD was associated independently with higher
      odds of having decreased eGFR (adjusted OR, 1.68; 95% CI, 1.52-1.86). Random
      coefficient models showed that individuals with parental CVD had a faster decline
      in eGFR compared with those without parental CVD (sex- and ethnicity-adjusted
      annual change of -0.47 vs -0.41 mL/min/1.73 m(2); P=0.06). LIMITATIONS: ~70% of
      participants did not attend a second examination. CONCLUSIONS: Parental history
      of CVD was associated with lower baseline eGFR, higher odds of decreased eGFR,
      and a nominally faster rate of eGFR decline in the offspring. Such findings may
      imply previously unrecognized cross-generational links between both diseases and
      be of support in community screening programs.

PMID- 25600490
TI  - Kidney disease and maternal and fetal outcomes in pregnancy.
AB  - BACKGROUND: Pregnancy in kidney disease is considered high risk, but the degree
      of this risk is unclear. We tested the hypothesis that kidney disease in
      pregnancy is associated with adverse maternal and fetal outcomes. STUDY DESIGN:
      Retrospective study comparing pregnant women with and without kidney disease.
      SETTING & PARTICIPANTS: Using data from an integrated health care delivery system
      from 2000 through 2013, a total of 778 women met the criteria for kidney disease.
      Using a pool of 74,105 women without kidney disease, we selected 778 women to use
      for matches for the women with kidney disease. These women were matched 1:1 by
      age, race, and history of diabetes, chronic hypertension, liver disease, and
      connective tissue disease. PREDICTOR: Kidney disease was defined using the NKF
      KDOQI definition for chronic kidney disease or International Classification of
      Diseases, Ninth Revision codes prior to pregnancy or serum creatinine level >
      1.2mg/dL and/or proteinuria in the first trimester. OUTCOMES & MEASUREMENTS:
      Maternal outcomes included preterm delivery, delivery by cesarean section,
      preeclampsia/eclampsia, length of stay at hospital (>3 days), and maternal death.
      Fetal outcomes included low birth weight (weight < 2,500g), small for gestational
      age, number of admissions to neonatal intensive care unit, and infant death.
      RESULTS: Compared with women without kidney disease, those with kidney disease
      had 52% increased odds of preterm delivery (OR, 1.52; 95% CI, 1.16-1.99) and 33%
      increased odds of delivery by cesarean section (OR, 1.33; 95% CI, 1.06-1.66).
      Infants born to women with kidney disease had 71% increased odds of admission to
      the neonatal intensive care unit or infant death compared with infants born to
      women without kidney disease (OR, 1.71; 95% CI, 1.17-2.51). Kidney disease also
      was associated with 2-fold increased odds of low birth weight (OR, 2.38; 95% CI,
      1.64-3.44). Kidney disease was not associated with increased risk of maternal
      death. LIMITATIONS: Data for level of kidney function and cause of death not
      available. CONCLUSIONS: Kidney disease in pregnancy is associated independently
      with adverse maternal and fetal outcomes when other comorbid conditions are
      controlled by matching.

PMID- 25600491
TI  - Can brief alcohol interventions for youth also address concurrent illicit drug
      use? results from a meta-analysis.
AB  - Brief interventions aimed at reducing alcohol use among youth may interrupt a
      possible developmental progression to more serious substance use if they can also
      affect the use of other illicit drugs. This meta-analysis examined the findings
      of recent research on the effects of brief alcohol interventions for adolescents
      and young adults on both alcohol and illicit drug use. Eligible studies were
      those using randomized or controlled quasi-experimental designs to examine the
      effects of brief alcohol interventions on illicit drug use outcomes among youth.
      A comprehensive literature search identified 30 eligible study samples that, on
      average, included participants age 17, with 57 % male participants and 56 % White
      youth. Three-level random-effects meta-analyses were used to estimate mean effect
      sizes and explore variability in effects. Overall, brief interventions targeting
      both alcohol and other drugs were effective in reducing both of these substances.
      However, the brief interventions that targeted only alcohol had no significant
      secondary effects on untargeted illicit drug use. The evidence from current
      research, therefore, shows modest beneficial effects on outcomes that are
      targeted by brief interventions for youth, but does not show that those effects
      generalize to untargeted illicit drug use outcomes. 

PMID- 25600492
TI  - Preventive effect of Pueraria mirifica on testosterone-induced prostatic
      hyperplasia in Sprague Dawley rats.
AB  - Pueraria mirifica (PM) extract contains phytoestrogen daidzein and genistein. In
      this study, we investigated the protective effect of PM extract, daidzein and
      genistein on a testosterone-induced prostatic hyperplasia in rats. Testosterone
      was administered at 3 mg kg(-1) to rats followed by the PM extract, daidzein and
      genistein for a period of 30 days with finasteride as positive control. The
      testosterone level was increased, indicating inhibition of 5alpha-reductase
      converting testosterone to dihydrotestosterone. This was confirmed by prostate
      specific antigen level that significantly decreased when treated with PM extract,
      daidzein and genistein. The PM extract, daidzein and genistein reduced the
      increase in the prostate/body weight ratio in testosterone-induced rats. This
      gives indication that PM extract, daidzein and genistein possessed protective
      activity for the treatment of benign prostatic hyperplasia. The analysis of
      histoarchitechture of the prostate has also shown that there was a significant
      improvement in prostatic cells of the testosterone-induced rats when treated with
      PM extract, daidzein and genistein.

PMID- 25600493
TI  - Does age affect gastric emptying time? A model-based meta-analysis of data from
      premature neonates through to adults.
AB  - PURPOSE: Gastric emptying (GE) is often reported to be slower and more irregular
      in premature neonates than in older children and adults. The aim of this study
      was to investigate the impact of age and other covariates on the rate of GE.
      METHODS: The effect of age on the mean gastric residence times (MGRT) of liquid
      and solid food was assessed by analysing 49 published studies of 1457
      individuals, aged from 28 weeks gestation to adults. The data were modelled using
      the nonlinear mixed-effects approach within NONMEM version 7.2 (ICON, Dublin,
      Ireland), with evaluation of postnatal age, gestational age and meal type as
      covariates. A double Weibull function was selected as a suitable model since it
      could account for the typical biphasic nature of GE. RESULTS: Age was not a
      significant covariate for GE but meal type was. Aqueous solutions were associated
      with the fastest emptying time (mean simulated gastric residence time of 45 min)
      and solid food was associated with the slowest (98 min). CONCLUSIONS: These
      findings challenge the assertion that GE is different in neonates, as compared
      with older children and adults due to age, and they reinforce the significance of
      food type in modulating GE.

PMID- 25600494
TI  - A gut microbial metabolite of ginsenosides, compound K, induces intestinal
      glucose absorption and Na(+) /glucose cotransporter 1 gene expression through
      activation of cAMP response element binding protein.
AB  - SCOPE: The Na(+) /glucose cotransporter 1 (SGLT1) plays a crucial role in glucose
      uptake in intestinal epithelial cells (IECs), which has been shown essential in
      ameliorating intestinal inflammation. Ginseng has historically been used to treat
      inflammatory disorders. Understanding the regulatory mechanism of ginseng
      mediated induction of SGLT1 gene expression in human intestinal cells is
      therefore important. METHODS AND RESULTS: We demonstrate that ginsenoside
      compound K (CK) enhances SGLT1-mediated glucose uptake in mice and human
      intestinal Caco-2 cells. Transient transfection analysis using SGLT1 promoter
      luciferase reporters demonstrated that the presence of an essential cAMP response
      element (CRE) is required for CK-mediated induction of SGLT1 gene expression. The
      ChIP assays indicated that increased CRE-binding protein (CREB) and CREB-binding
      protein (CBP) binding to the SGLT1 promoter in CK-treated cells is associated
      with an activated chromatin state. Our result showed that the increased CREB
      phosphorylation is directly correlated with SGLT1 expression in IECs. Further
      studies indicated that the epidermal growth factor receptor (EGFR) signaling
      pathway is involved in the CK-mediated effect. CONCLUSION: These findings provide
      a novel mechanism for the CK-mediated upregulation of SGLT1 expression through
      EGFR-CREB signaling activation, which could contribute to reducing gut
      inflammation.

PMID- 25600496
TI  - Human factors assessment of conflict resolution aid reliability and time pressure
      in future air traffic control.
AB  - Though it has been reported that air traffic controllers' (ATCos') performance
      improves with the aid of a conflict resolution aid (CRA), the effects of
      imperfect automation on CRA are so far unknown. The main objective of this study
      was to examine the effects of imperfect automation on conflict resolution. Twelve
      students with ATC knowledge were instructed to complete ATC tasks in four CRA
      conditions including reliable, unreliable and high time pressure, unreliable and
      low time pressure, and manual conditions. Participants were able to resolve the
      designated conflicts more accurately and faster in the reliable versus unreliable
      CRA conditions. When comparing the unreliable CRA and manual conditions,
      unreliable CRA led to better conflict resolution performance and higher situation
      awareness. Surprisingly, high time pressure triggered better conflict resolution
      performance as compared to the low time pressure condition. The findings from the
      present study highlight the importance of CRA in future ATC operations.
      Practitioner Summary: Conflict resolution aid (CRA) is a proposed automation
      decision aid in air traffic control (ATC). It was found in the present study that
      CRA was able to promote air traffic controllers' performance even when it was not
      perfectly reliable. These findings highlight the importance of CRA in future ATC
      operations. 

PMID- 25600495
TI  - Rapid biodiagnostic ex vivo imaging at 1 MUm pixel resolution with thermal source
      FTIR FPA.
AB  - A recent upgrade to the optics configuration of a thermal source FTIR microscope
      equipped with a focal plane array detector has enabled rapid acquisition of high
      magnification spectrochemical images, in transmission, with an effective
      geometric pixel size of ~1 * 1 MUm(2) at the sample plane. Examples, including
      standard imaging targets for scale and accuracy, as well as biomedical tissues
      and microorganisms, have been imaged with the new system and contrasted with data
      acquired at normal magnification and with a high magnification multi-beam
      synchrotron instrument. With this optics upgrade, one can now conduct rapid
      biodiagnostic ex vivo tissue imaging in-house, with images collected over larger
      areas, in less time (minutes) and with comparable quality and resolution to the
      best synchrotron source FTIR imaging capabilities. 

PMID- 25600497
TI  - Aqueous black colloids of reticular nanostructured gold.
AB  - Since ancient times, noble gold has continuously contributed to several aspects
      of life from medicine to electronics. It perpetually reveals its new features. We
      report the finding of a unique form of gold, reticular nanostructured gold (RNG),
      as an aqueous black colloid, for which we present a one-step synthesis. The
      reticules consist of gold crystals that interconnect to form compact strands. RNG
      exhibits high conductivity and low reflection, and these features, coupled with
      the high specific surface area of the material, could prove valuable for
      applications in electronics and catalysis. Due to high absorption throughout the
      visible and infrared domain, RNG has the potential to be applied in the
      construction of sensitive solar cells or as a substrate for Raman spectroscopy. 

PMID- 25600498
TI  - Reply to Letter to the Editor - Leptin levels in Gaucher disease type I patients:
      A methodological approach.

PMID- 25600499
TI  - [Saccular aneurysm of the azygos vein in a patient with azygos accessory
      fissure].
AB  - The saccular aneurysm of the azygos vein is an extremely rare condition, which
      when located in the path of an accesory pulmonary fissure, becomes a diagnostic
      challenge because it can be mistaken for tumors arising from the accesory pleura,
      like solitary fibrous tumor of the pleura or mesothelioma. The diagnosis should
      ideally be done by non-invasive methods such as CT or MR angiographic technique
      in multiple phases, thus avoiding unnecessary surgical intervention. This case is
      exceptional because, to our knowledge, it is the first to report both concomitant
      clinical situations, an aneurysm of the azygos vein in the pathway of its
      accessory fissure. 

PMID- 25600500
TI  - The developmental origins of spatial navigation: are we headed in the right
      direction?
AB  - Navigation depends upon neural systems that monitor spatial location and head
      orientation. Recent developmental findings have led some to conclude that these
      systems are innate. Such claims are premature. But also, there are more
      meaningful ways to arrive at answers about developmental origins than by invoking
      the outdated nature-nurture dichotomy. 

PMID- 25600501
TI  - Phylogeny of genetic codes and punctuation codes within genetic codes.
AB  - Punctuation codons (starts, stops) delimit genes, reflect translation apparatus
      properties. Most codon reassignments involve punctuation. Here two complementary
      approaches classify natural genetic codes: (A) properties of amino acids assigned
      to codons (classical phylogeny), coding stops as X (A1,
      antitermination/suppressor tRNAs insert unknown residues), or as gaps (A2, no
      translation, classical stop); and (B) considering only punctuation status (start,
      stop and other codons coded as -1, 0 and 1 (B1); 0, -1 and 1 (B2, reflects
      ribosomal translational dynamics); and 1, -1, and 0 (B3, starts/stops as
      opposites)). All methods separate most mitochondrial codes from most nuclear
      codes; Gracilibacteria consistently cluster with metazoan mitochondria;
      mitochondria co-hosted with chloroplasts cluster with nuclear codes. Method A1
      clusters the euplotid nuclear code with metazoan mitochondria; A2 separates
      euplotids from mitochondria. Firmicute bacteria Mycoplasma/Spiroplasma and
      Protozoan (and lower metazoan) mitochondria share codon-amino acid assignments.
      A1 clusters them with mitochondria, they cluster with the standard genetic code
      under A2: constraints on amino acid ambiguity versus punctuation-signaling
      produced the mitochondrial versus bacterial versions of this genetic code.
      Punctuation analysis B2 converges best with classical phylogenetic analyses,
      stressing the need for a unified theory of genetic code punctuation accounting
      for ribosomal constraints. 

PMID- 25600502
TI  - Germline RAD51B truncating mutation in a family with cutaneous melanoma.
AB  - Known melanoma predisposition genes only account for around 40% of high-density
      melanoma families. Other rare mutations are likely to play a role in melanoma
      predisposition. RAD51B plays an important role in DNA repair through homologous
      recombination, and inactivation of RAD51B has been implicated in tumorigenesis.
      Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a
      germline splicing mutation in RAD51B has been identified in a family with early
      onset breast cancer. In order to find genetic variants associated with melanoma
      predisposition, whole-exome sequencing was carried out on blood samples from a
      three-case cutaneous melanoma family. We identified a novel germline RAD51B
      nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma
      cells indicating inactivation of RAD51B. This is only the second report of a
      germline truncating RAD51B mutation. While this case report is consistent with
      melanoma being part of the RAD51B cancer spectrum further population-based
      screening of large case-control sample series will be needed to definitively
      establish if this is the case.

PMID- 25600503
TI  - Cyclopalladated complexes containing 2-C6R4PPh2 ligands (R = H, F): one-electron
      electrochemical reduction leading to metal-carbon sigma-bond cleavage via
      palladium(I).
AB  - Three new ortho-metallated palladium complexes, [Pd(O,O'-hfacac)(kappa(2)-2
      C6F4PPh2)] (), [Pd2(O,O'-hfacac)2(MU-2-C6F4PPh2)2] () and [Pd(O,O'-hfacac)(kappaC
      2-C6F4PPh2)(PPh3)] () (hfacac = hexafluoroacetylacetonate), have been prepared
      and fully characterised. The electrochemical reductions of complexes , together
      with those of other cyclopalladated complexes containing 2-C6R4PPh2 ligands (R =
      H, F) were studied by cyclic, rotating disk and microelectrode voltammetry.
      Evidence for the one-electron reduction of [PdI(kappa(2)-2-C6F4PPh2)(PPh2Fc)] ()
      was obtained from coulometric analysis, although the product is unstable and
      undergoes further chemical processes. Preparative electro-reduction of [Pd2(MU
      Br)2(kappa(2)-2-C6F4PPh2)2] () in CH2Cl2 causes reductive cleavage of its Pd-C
      sigma-bonds and formation of the complex [PdBr2{PPh2(2-C6F4H)}2] (); possible
      mechanisms are discussed. 

PMID- 25600504
TI  - Is the TNM staging system for breast cancer still relevant in the era of
      biomarkers and emerging personalized medicine for breast cancer - an
      institution's 10-year experience.
AB  - We have previously demonstrated that TNM status and age were significant
      predictors of overall survival (OS) in our study population of Caucasian patients
      with invasive breast carcinoma (2000-2004 study period). However, estrogen
      receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2
      (HER2) biomarker expression was not predictive of OS when using the five-group
      ER/PR/HER2 subtype classification system recommended by St. Gallen International
      Consensus Panel in 2011. The current study reassessed the relevance of tumor
      biomarkers (ER/PR/HER2) in our study population using a recently proposed
      biologic TNM (bTNM) classification system in which the inclusion of triple
      negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM
      for staging, prognosis and treatment of breast cancer patients. Seven hundred
      eighty-two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to
      2008 were grouped according to their TNM stage and TNP versus non-TNP ER/PR/HER2
      phenotype. OS was measured comparing these categories using Kaplan Meier curves
      and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01-1.97;
      Stage III = HR 3.96, 95% CI 2.68-5.88; Stage IV = HR 27.25, 95% CI 16.84-44.08),
      and age (HR 1.05, 95% CI 1.04-1.06) were significant predictors of OS. TNP
      significantly worsened prognosis/survival only in higher TNM stages (Stage III =
      HR 3.08, 95% CI 1.88-5.04, Stage IV = HR 24.36, 95% CI 13.81-42.99), but not in
      lower stages (I and II). Our data support the traditional TNM staging as a
      continued relevant predictive tool for breast cancer outcomes and show that
      biomarkers primarily improve the accuracy of TNM staging in advanced stages of
      breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St.
      Gallen, TNP, etc.), characteristics of populations studied (Caucasians,
      minorities, etc.), and the time period chosen for a study are major factors that
      determine impact of biomarkers on the prognostic accuracy of TNM. We propose
      systematic analyses of these factors before biomarkers are fully incorporated
      into the TNM staging system (bTNM).

PMID- 25600505
TI  - Insights into the structure of intrastrand cross-link DNA lesion-containing
      oligonucleotides: G[8-5m]T and G[8-5]C from molecular dynamics simulations.
AB  - Oxidatively generated complex DNA lesions occur more rarely than single
      nucleotide defects, yet they play an important role in carcinogenesis and aging
      diseases because they have proved to be more mutagenic than simple lesions.
      Whereas their formation pathways are rather well understood, the field suffers
      from the absence of structural data that are crucial for interpreting the lack of
      repair. No experimental structures are available for oligonucleotides featuring
      such a lesion. Hence, the detailed structural basis of such damaged duplexes has
      remained elusive. We propose the use of explicit solvent molecular dynamics
      simulations to build up damaged oligonucleotides containing two intrastrand cross
      link defects, namely, the guanine-thymine and guanine-cytosine defects. Each of
      these lesions, G[8-5m]T and G[8-5]C, is placed in the middle of a dodecameric
      sequence, which undergoes an important structural rearrangement that we monitor
      and analyze. In both duplexes, the structural evolution is dictated by the more
      favorable stacking of guanine G6, which aims to restore pi-stacking with the 3'
      purine nucleobase. Subsequently, transient formation of hydrogen bonds with a
      strand shifting is observed. Our simulations are combined with density functional
      theory to rationalize the structural evolution. We report converging
      computational evidence that the G[8-5m]T- and G[8-5]C-containing structures
      evolve toward "abasic-like" duplexes, with a stabilization of the interstrand
      pairing noncovalent interactions. Meanwhile, both lesions restore B-helicity
      within tens of nanoseconds. The identification of plausible structures
      characterizes the last hydrogen abstraction step toward the formation of such
      defects as a non-innocent chemical reaction.

PMID- 25600506
TI  - Application of a semi-empirical model for the evaluation of transmission
      properties of barite mortar.
AB  - The aim of this study was to estimate barite mortar attenuation curves using X
      ray spectra weighted by a workload distribution. A semi-empirical model was used
      for the evaluation of transmission properties of this material. Since ambient
      dose equivalent, H(*)(10), is the radiation quantity adopted by IAEA for dose
      assessment, the variation of the H(*)(10) as a function of barite mortar
      thickness was calculated using primary experimental spectra. A CdTe detector was
      used for the measurement of these spectra. The resulting spectra were adopted for
      estimating the optimized thickness of protective barrier needed for shielding an
      area in an X-ray imaging facility. 

PMID- 25600507
TI  - Evaluation of characteristic-to-total spectrum ratio: Comparison between
      experimental and a semi-empirical model.
AB  - Primary X-ray spectra were measured in the range of 80-150kV in order to validate
      a computer program based on a semiempirical model. The ratio between the
      characteristic and total air Kerma was considered to compare computed results and
      experimental data. Results show that the experimental spectra have higher first
      HVL and mean energy than the calculated ones. The ratios between the
      characteristic and total air Kerma for calculated spectra are in good agreement
      with experimental results for all filtrations used. 

PMID- 25600508
TI  - Return on investment in electronic health records in primary care practices: a
      mixed-methods study.
AB  - BACKGROUND: The use of electronic health records (EHR) in clinical settings is
      considered pivotal to a patient-centered health care delivery system. However,
      uncertainty in cost recovery from EHR investments remains a significant concern
      in primary care practices. OBJECTIVE: Guided by the question of "When implemented
      in primary care practices, what will be the return on investment (ROI) from an
      EHR implementation?", the objectives of this study are two-fold: (1) to assess
      ROI from EHR in primary care practices and (2) to identify principal factors
      affecting the realization of positive ROI from EHR. We used a break-even point,
      that is, the time required to achieve cost recovery from an EHR investment, as an
      ROI indicator of an EHR investment. METHODS: Given the complexity exhibited by
      most EHR implementation projects, this study adopted a retrospective mixed-method
      research approach, particularly a multiphase study design approach. For this
      study, data were collected from community-based primary care clinics using EHR
      systems. RESULTS: We collected data from 17 primary care clinics using EHR
      systems. Our data show that the sampled primary care clinics recovered their EHR
      investments within an average period of 10 months (95% CI 6.2-17.4 months),
      seeing more patients with an average increase of 27% in the active-patients-to
      clinician-FTE (full time equivalent) ratio and an average increase of 10% in the
      active-patients-to-clinical-support-staff-FTE ratio after an EHR implementation.
      Our analysis suggests, with a 95% confidence level, that the increase in the
      number of active patients (P=.006), the increase in the active-patients-to
      clinician-FTE ratio (P<.001), and the increase in the clinic net revenue (P<.001)
      are positively associated with the EHR implementation, likely contributing
      substantially to an average break-even point of 10 months. CONCLUSIONS: We found
      that primary care clinics can realize a positive ROI with EHR. Our analysis of
      the variances in the time required to achieve cost recovery from EHR investments
      suggests that a positive ROI does not appear automatically upon implementing an
      EHR and that a clinic's ability to leverage EHR for process changes seems to play
      a role. Policies that provide support to help primary care practices successfully
      make EHR-enabled changes, such as support of clinic workflow optimization with an
      EHR system, could facilitate the realization of positive ROI from EHR in primary
      care practices.

PMID- 25600509
TI  - Effects of dietary chlorogenic acid on growth performance, antioxidant capacity
      of white shrimp Litopenaeus vannamei under normal condition and combined stress
      of low-salinity and nitrite.
AB  - An eight-week feeding trial followed by an acute combined stress test of low
      salinity and nitrite were performed to evaluate effects of chlorogenic acid (CGA)
      on growth performance and antioxidant capacity of white shrimp Litopenaeus
      vannamei. Shrimp were randomly allocated in 12 tanks (30 shrimp per tank) and
      triplicate tanks were fed with a control diet or diets containing different
      levels of CGA (100, 200 and 400 mg kg(-1) feed) as treatment groups. Growth
      performance including weight gain (WG), biomass gain (BG), feed conversion ratio
      (FCR), and feed intake were determined after feeding for 56 days. Antioxidant
      capacity were evaluated by determining the activity of total antioxidant status
      (TAS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase
      (CAT) as well as the gene expression of GSH-Px and CAT in the hepatopancreas of
      shrimp at the end of feeding trial and again at the end of the combined stress
      test. The results indicated that supplemention of CGA had no significant effects
      on the growth performance and the activities of TAS, SOD, GSH-Px and CAT in
      hepatopancreas of shrimp cultured under normal conditions for 56 days. However,
      compared with the control group, CGA (200, 400 mg kg(-1) feed) significantly
      improved the resistance of L. vannamei against the combined stress of low
      salinity and nitrite, as indicated by the significant (P < 0.05) higher survival,
      higher activities of TAS, GSH-Px and CAT, as well as higher transcript levels of
      GPx and CAT gene in shrimp treated with CGA in the combined tress test. Our
      findings suggested that CGA possessed dual-modulatory effects on antioxidant
      capacity of L. vannamei and could be a potential feed additive that can enhance
      shrimp resistance against environmental stresses. The recommended application
      dosage is 200 mg kg(-1) and further studies are needed to clarify the action
      model of CGA efficiency. 

PMID- 25600511
TI  - International note: exploring differences in native and immigrant adolescents'
      mathematics achievement and dispositions towards mathematics in Qatar.
AB  - The burgeoning immigrant population in major immigrant-receiving countries in
      North America and Europe has necessitated researchers and policymakers in these
      countries to examine the academic success of children of immigration and the
      factors contributing to their academic success. However, there is sparse research
      on the academic trajectories of children of immigration in other continents, such
      as Asia. Hence, the purpose of the present study was to examine first- and second
      generation immigrant adolescents' mathematics achievement and dispositions
      towards mathematics in comparison to their native peers in one of the Middle
      Eastern countries in Asia, Qatar. The results of the study indicated that both
      first- and second-generation immigrant adolescents tended to have higher
      mathematics achievement, intrinsic motivation to learn mathematics, instrumental
      motivation to learn mathematics, mathematics self-efficacy, and mathematics self
      concept than did their native counterparts. Moreover, immigrant adolescents
      tended to have lower mathematics anxiety than did their native peers. The study
      also revealed significant differences between first- and second-generation
      immigrant adolescents with respect to their mathematics achievement and
      dispositions towards mathematics. 

PMID- 25600510
TI  - Service use patterns and mental health symptoms among adolescents exposed to
      multiple types of trauma.
AB  - Few studies have explored how different trauma experiences influence service use.
      This study explores patterns of service use amongst 6483 adolescents aged between
      13 and 18, and examines if such patterns are associated with trauma profiles,
      demographic variables, and mental health disorders. Data from the National
      Comorbidity Survey--Adolescent Supplement (NCS-A) were used. A latent class
      analysis identified four adolescent trauma sub-groups: 'high risk', 'sexual risk'
      'non-sexual risk', and 'low risk'. Regression analysis was used to explore the
      relationship between service use, trauma classes, and mental health outcomes.
      Significant relationships were found between service use, trauma sub-groups,
      demographics and mental health outcomes. Despite the effectiveness of mental
      health services, only a minority of adolescents exposed to different traumas use
      such resources. However, this study may go some way towards providing an
      understanding of the trauma backgrounds, demographic predictors and mental health
      disorders associated with service use.

PMID- 25600512
TI  - Emotion regulation and depressive symptoms: examining the mediation effects of
      school connectedness in Chinese late adolescents.
AB  - This study tested Gross's process model of emotion regulation in a Chinese
      adolescent sample. It hypothesized that emotion regulation strategies (cognitive
      reappraisal and expressive suppression) would predict adolescents' perception of
      school connectedness and depressive symptoms. It also posited that school
      connectedness may be a possible mediator between emotion regulation and
      depressive symptoms. Participants were 504 adolescents aged 16-18 from two
      Chinese public upper secondary schools. Structural equation modeling analyses
      indicated that reappraisal and suppression significantly associated with school
      connectedness and depressive symptoms, and school connectedness mediated the link
      between emotion regulation and depressive symptoms, even when the general emotion
      experiences were controlled. Although boys unexpectedly reported higher level
      depressive symptoms, the hypothesized model was invariant across gender except
      for the link between suppression and depressive symptoms. These findings
      demonstrate that it is meaningful to involve both emotion regulation processes
      and school connectedness in explaining adolescent depressive symptoms. 

PMID- 25600513
TI  - Guideline of guidelines: a review of urological trauma guidelines.
AB  - OBJECTIVE: To review the guidelines released in the last decade by several
      organisations for the optimal evaluation and management of genitourinary injuries
      (renal, ureteric, bladder, urethral and genital). METHODS: This is a review of
      the genitourinary trauma guidelines from the European Association of Urology
      (EAU) and the American Urological Association (AUA), and renal trauma guidelines
      from the Societe Internationale d'Urologie (SIU). RESULTS: Most recommendations
      are guided by the American Association for the Surgery of Trauma (AAST) organ
      injury severity system. Grade A evidence is rare in genitourinary trauma, and
      most recommendations are based on Grade B or C evidence. The findings of the most
      recent urological trauma guidelines are summarised. All guidelines recommend
      conservative management for low-grade injuries. The major difference is for
      haemodynamically stable patients who have high-grade renal trauma; the SIU
      guidelines recommend exploratory laparotomy, the EAU guidelines recommend renal
      exploration only if the injury is vascular, and the AUA guidelines recommend
      initial conservative management. CONCLUSION: There is generally consensus among
      the three guidelines. Recommendations are based on observational or retrospective
      studies, as well as clinical principles and expert opinions. Multi-institutional
      collaborative research can improve the quality of evidence and direct more
      effective evaluation and management of urological trauma.

PMID- 25600514
TI  - Decreased circulating neopterin is associated with increased arterial elasticity:
      a beneficial role of periodontal treatment.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of periodontal
      treatment on arterial elasticity and circulating neopterin in patients with
      moderate to severe periodontitis in a Chinese population. METHODS: One hundred
      and eight patients with moderate to severe periodontitis were eligible to take
      part in the study and were randomized into two groups. The treatment group
      received intensive periodontal treatment, while the control group received
      control periodontal treatment. All parameters, including brachial-ankle pulse
      wave velocity (baPWV), ankle brachial index (ABI), serum neopterin (NP), high
      sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), were evaluated
      before treatment and 1 month after treatment. RESULTS: The parameters including
      NP, hs-CRP, IL-6 and baPWV decreased significantly after 1 month in the treatment
      group (p < 0.05 for all comparisons) but not in the control group (p > 0.05).
      There was no significant difference in the change of ABI between the two groups
      (p = 0.231). A positive correlation was found between the decreased circulating
      NP and increased arterial elasticity in the treatment group (r = 0.947, p <
      0.001). CONCLUSIONS: This study demonstrates for the first time that the fall in
      circulating NP induced by periodontal treatment contributes to increased arterial
      elasticity in patients with moderate and severe periodontitis.

PMID- 25600515
TI  - Group versus individual interpersonal psychotherapy for depressed adolescents.
AB  - BACKGROUND: This study adds to the limited evidence concerning the benefits of
      Interpersonal Psychotherapy (IPT) with depressed adolescents. It evaluates the
      long-term effects of group versus individual delivery of this treatment approach.
      AIMS: To conduct a small-scale examination of the long-term efficacy of group
      versus individual delivery of IPT for depressed adolescents. METHOD: Thirty-nine
      adolescents, aged 13-19 years, with a primary diagnosis of Major Depressive
      Disorder, were randomly assigned in blocks to either group or individual delivery
      of IPT. Standardized clinical interview and questionnaire assessments were
      conducted at pre- and posttreatment, and 12-month follow-up. RESULTS: Intent-to
      treat (ITT) analyses indicated significant improvements in depression, anxiety,
      youth-reported internalizing problems, and global functioning from pre- to
      posttreatment for those receiving IPT, with no significant differences in outcome
      between group and individual formats of delivery. Improvements were maintained at
      12-month follow-up. Completer analyses also revealed significant and sustained
      improvements on these measures for those receiving IPT, with no differences in
      outcome between therapy formats for most measures. Individual IPT showed
      significantly greater improvements than group IPT in parent-reported
      internalizing problems for the completer but not the ITT analyses. CONCLUSIONS:
      Both individual and group formats of IPT offer promise in producing long-term
      benefits in the treatment of depression among adolescents.

PMID- 25600516
TI  - A systematic review and meta-analysis of Ginsenoside-Rg1 (G-Rg1) in experimental
      ischemic stroke.
AB  - The neuroprotective actions of Ginsenoside-Rg1 (G-Rg1) have been documented for
      experimental stroke therapy. We used a systematic review and meta-analysis to
      assess the efficacy of G-Rg1 in experimental ischemic stroke. We identified
      studies describing the efficacy of G-Rg1 in animal models of focal cerebral
      ischemia. Primary outcomes were infarct volume and neurological function score
      (NFS). In all, eleven studies reported significant effects of G-Rg1 for improving
      the NFS when compared with the control group (P < 0.00001), and four studies
      reported significant effects of G-Rg1 for reducing infarct volume compared with
      middle cerebral artery occlusion group (P < 0.00001). Meanwhile, studies reported
      G-Rg1 was more efficacious than positive control drug nimodipine (0.7 or 1 mg/kg,
      intraperitoneal) according to NFS (P = 0.009) and infarct volume (p = 0.0002).
      The results demonstrate a marked efficacy of G-Rg1 in experimental acute ischemic
      stroke, but raise concerns that our value of effect size might be overestimate
      due to factors such as study quality and possible publication bias. Even so, the
      findings suggest G-Rg1 as a candidate neuroprotective drug for human ischemic
      stroke.

PMID- 25600517
TI  - Scutellarin regulates the Notch pathway and affects the migration and
      morphological transformation of activated microglia in experimentally induced
      cerebral ischemia in rats and in activated BV-2 microglia.
AB  - BACKGROUND: Activated microglial cells release an excess of inflammatory
      mediators after an ischemic stroke. We reported previously that scutellarin
      effectively suppressed the inflammatory response induced by activated microglia
      in rats subjected to middle cerebral artery occlusion (MCAO); however, the
      mechanism via which scutellarin exerts its effects on microglial activation has
      not been explored. This study aimed to elucidate if scutellarin can regulate the
      Notch pathway that is linked to microglia activation in MCAO rat, and in
      lipopolysaccharide (LPS)-induced BV-2 microglia. Along with this, we also
      investigated some characteristic behavioral responses of activated microglia.
      METHODS: Expression of various members of the Notch pathway, including Notch-1,
      intracellular Notch receptor domain (NICD), recombining binding protein
      suppressor of hairless (RBP-JK) and transcription factor hairy and enhancer of
      split-1 (Hes-1) in activated microglia was assessed by immunofluorescence
      staining and western blot after experimental MCAO and in vitro LPS activation.
      The effect of scutellarin on migration of microglia was determined by the
      transwell chamber assay as well as expression of monocyte chemoattractant protein
      1 (MCP-1). The morphological change of microglia induced by scutellarin was
      detected by F-actin staining and electron microscopy. RESULTS: Scutellarin
      markedly attenuated the expression of NF-kappaB, Notch-1, NICD, RBP-JK and Hes-1
      both in vivo and in activated microglia. It decreased the expression of MCP-1 and
      microglial migration, but increased the ability of microglia adhesion.
      Scutellarin also altered the phenotype of microglia by causing rearrangement or
      reorganization of its cytoskeleton. CONCLUSIONS: The results suggest that
      scutellarin regulates the activation of microglia via the Notch pathway and
      concurrently induces morphological and functional changes in activated microglia.

PMID- 25600518
TI  - Well-Hidden Regularities: Abstract Uses of in and on Retain an Aspect of Their
      Spatial Meaning.
AB  - Prepositions name spatial relationships (e.g., book on a table). But they are
      also used to convey abstract, non-spatial relationships (e.g., Adrian is on a
      roll)-raising the question of how the abstract uses relate to the concrete
      spatial uses. Despite considerable success in delineating these relationships, no
      general account exists for the two most frequently extended prepositions: in and
      on. We test the proposal that what is preserved in abstract uses of these
      prepositions is the relative degree of control between the located object (the
      figure) and the reference object (the ground). Across four experiments, we find a
      continuum of greater figure control for on (e.g., Jordan is on a roll) and
      greater ground control for in (e.g., Casey is in a depression). These findings
      bear on accounts of semantic structure and language change, as well as on second
      language instruction. 

PMID- 25600520
TI  - Open vial policy in India-a commentary.

PMID- 25600519
TI  - Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases: a systematic
      review and implications for polio eradication.
AB  - BACKGROUND: Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated
      from the oral polio vaccine, pose a challenge to global polio eradication.
      Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV
      which may serve as sources of poliovirus reintroduction after the eradication of
      wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV
      cases published in the scientific literature from 1962 to 2012, and describes
      clinically relevant trends in reported iVDPV cases worldwide. METHODS: We
      conducted a systematic review of published iVDPV case reports from January 1960
      to November 2012 from four databases. We included cases in which the patient had
      a primary immunodeficiency, and the vaccine virus isolated from the patient
      either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and
      3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the
      World Health Organization. RESULTS: We identified 68 iVDPV cases in 49
      manuscripts reported from 25 countries and the Palestinian territories. 62% of
      case patients were male, 78% presented clinically with acute flaccid paralysis,
      and 65% were iVDPV2. 57% of cases occurred in patients with predominantly
      antibody immunodeficiencies, and the overall all-cause mortality rate was greater
      than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the
      median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a
      poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median
      percent divergence for iVDPV1 cases. More cases were reported from high income
      countries, which also had a larger age variation and different distribution of
      immunodeficiencies compared to upper and lower middle-income countries.
      CONCLUSION: Our study describes the incidence and characteristics of global iVDPV
      cases reported in the literature in the past five decades. It also highlights the
      regional and economic disparities of reported iVDPV cases.

PMID- 25600521
TI  - The Ten Group Classification System (TGCS) - a common starting point for more
      detailed analysis.

PMID- 25600522
TI  - Curcumin suppression of cytokine release and cytokine storm. A potential therapy
      for patients with Ebola and other severe viral infections.
AB  - BACKGROUND: The terminal stage of Ebola and other viral diseases is often the
      onset of a cytokine storm, the massive overproduction of cytokines by the body's
      immune system. MATERIALS AND METHODS: The actions of curcumin in suppressing
      cytokine release and cytokine storm are discussed. RESULTS: Curcumin blocks
      cytokine release, most importantly the key pro-inflammatory cytokines,
      interleukin-1, interleukin-6 and tumor necrosis factor-alpha. The suppression of
      cytokine release by curcumin correlates with clinical improvement in experimental
      models of disease conditions where a cytokine storm plays a significant role in
      mortality. CONCLUSION: The use of curcumin should be investigated in patients
      with Ebola and cytokine storm. Intravenous formulations may allow achievement of
      therapeutic blood levels of curcumin.

PMID- 25600523
TI  - Effect of radiation and repeated sub-culturing on the transforming growth factor
      beta1 signaling pathway in FRTL-5 cells.
AB  - BACKGROUND/AIM: Fisher rat thyroid cells (FRTL-5) display increased
      proliferation, reduced follicularization and decreased thyroxin release with
      repeated sub-culturing. These changes occur earlier and more rapidly following
      exposure to ionizing radiation. We hypothesized that altered transforming growth
      factor-beta1 (TGF-beta1) signaling contributes to these differences. MATERIALS
      AND METHODS: Assessments included FRTL-5 cell growth rate and quantification of
      TGF-beta1 ligand and receptors. The levels and activity of Smads2, 3 and 4 were
      measured by western blotting and the ability of TGF-beta1 to regulate cyclin A
      and plasminogen activator inhibitor type 1 (PAI-1) activity was assessed using
      transfection assays. RESULTS: TGF-beta1 production increased after radiation but
      returned to control levels after repeated sub-culturing. There was no difference
      in TGF-beta1 levels between un-irradiated cells at low versus high-passage
      number. TGF-beta1 receptors and basal levels of Smads2, 3 and 4 remained
      unchanged. However, there were significant changes in cell proliferation, TGF
      beta1-mediated Smads2 and 3 activation and in TGF-beta1's ability to regulate
      cyclin A and PAI-1 transcription in irradiated and repeatedly sub-cultured cells
      (p<0.05). CONCLUSION: Collectively, these results support the conclusion that
      alterations in the TGF-beta1 pathway contribute to phenotypic changes in FRTL-5
      cells as a function of passage number and radiation.

PMID- 25600524
TI  - Profiles of reproductive hormone in the microminipig during the normal estrous
      cycle.
AB  - We investigated changes in the peripheral plasma concentrations of ovarian
      steroids and gonadotropins throughout the estrous cycle of the Microminipig
      (MMpig), a novel experimental animal model. The mean (+/- standard error of the
      mean (SEM)) duration of estrous and the estrous cycle in seven animals was 66.0
      +/- 5.2 h and 20.6 +/- 0.3 days, respectively. A luteinizing hormone (LH) surge
      was observed 16.5 +/- 6.5 h after the onset of estrous in six out of the seven
      animals. The LH peak and the duration of the LH surge were 14.0 +/- 4.5 ng/ml and
      34.0 +/- 2.0 h, respectively. Plasma progesterone concentrations started to
      decline on Day 7 (Day 0 = the day of the LH peak) and increased from Day 4.
      Estradiol-17beta levels increased from Day 3 and reached a maximum (37.0 +/- 1.6
      pg/ml) on Day 0.75. Follicle-stimulating hormone (FSH) concentrations showed a
      first and second surge on Days 0 and 1.75. An inverse relationship between FSH
      and estradiol-17beta concentrations was noted before the LH surge. The
      characteristics of estrous and the gonadotropin and ovarian steroid profiles
      throughout the estrous cycle of MMpigs are similar to those of domestic pigs and
      other miniature pig strains.

PMID- 25600525
TI  - Altered expression of claudin-1 is related with malignancy in canine thyroid
      tumors.
AB  - BACKGROUND/AIM: Claudins (CLDNs) are crucial structural and functional components
      of tight junctions playing an important role in maintaining cell polarity,
      controlling paracellular diffusion and regulating cell growth and differentiation
      of epithelial cells. CLDNs are differentially expressed in neoplastic lesions
      compared to the corresponding healthy tissues; therefore, they are thought to
      play a role in tumorigenesis and tumor progression. Reduced expression of CLDN-1
      has been observed in several types of human cancers, including thyroid tumors.
      There are no reports of CLDN-1 immunoexpression in normal and neoplastic canine
      thyroid tissues. MATERIAL AND METHODS: CLDN-1 immunoexpression was investigated
      in normal canine thyroid gland (n=2), benign (n=1) and malignant (n=10) tumors,
      as well as neoplastic emboli (n=6). RESULTS: CLDN-1 was constitutively expressed
      in normal canine follicular epithelium. Ninety percent of the malignant canine
      thyroid lesions showed absence or reduced CLDN-1 expression compared to that of
      normal thyroid gland. Additionally, a cytoplasmic subcellular location of CLDN-1
      was recorded in the malignant epithelial cells and neoplastic emboli. CONCLUSION:
      These findings link altered expression of CLDN-1 to neoplastic transformation and
      suggest that CLDN-1 expression is associated with malignant canine thyroid tumors
      and their vascular invasion.

PMID- 25600526
TI  - Mast cells stimulate lymphangiogenesis in the gingiva of patients with
      periodontal disease.
AB  - The presence and distribution of lymphatic vessels and mast cells in the gingiva
      under normal and pathological conditions have been reported by several studies,
      but the relationship between them during inflammatory lymphangiogenesis is
      virtually unknown. The aim of the present study was to investigate the lymphatic
      microvessel density (LMVD) and mast cell density (MCD) in the gingiva of patients
      with periodontal disease compared to normal-like gingiva. Gingival punch biopsies
      from 51 patients with periodontal disease were investigated. MCs and LVs were
      detected by double-immunohistochemistry, using primary antibodies against mast
      cell tryptase and D2-40. The inflammatory infiltrate was evaluated on a scale
      from 0 (absent) to +3 (severe inflammation). MCs and LVs were counted in the same
      microscopic field for each case at *200 magnification. We found a significant
      increase in the number of both MCs and LVs in cases with mild and moderate
      inflammatory changes, followed by a slight decrease in cases with severe
      inflammation. We have shown a particular association between MCs and LVs that may
      support the contribution of MCs to the development of the lymphatic vasculature
      in inflammatory conditions. MCD correlated with LMVD in all cases with mild and
      moderate inflammatory changes, but not in cases with severe inflammation. No
      correlation was found between MCD/LMVD and the density of the inflammatory
      infiltrate. Our results suggest the potential involvement of MCs in the induction
      and maintenance of lymphangiogenesis in the gingiva of patients with periodontal
      disease in the early steps of evolution. 

PMID- 25600527
TI  - Xeroderma pigmentosum complementation group C protein (XPC) expression in basal
      cell carcinoma.
AB  - BACKGROUND: The Xeroderma pigmentosum complementation group C protein (XPC) is a
      general sensor of damaged DNA. Individuals carrying a mutation in XPC genes
      exhibit marked photosensitivity and increased occurrence of skin cancers. Little
      is known about the distribution of XPC protein in basal cell carcinoma (BCC).
      AIM: To determine whether the XPC protein is associated with basal cell
      carcinoma. MATERIALS AND METHODS: In the present study, we investigated the
      protein expression of XPC by immunohistochemistry in 86 cases of BCC and paired
      adjacent normal epidermis. RESULTS: The intensity of nuclear XPC expression was
      significantly higher in BCC compared to adjacent normal epidermis (p<0.001).
      Attenuated XPC expression was associated with high-risk BCC (p=0.045) but was not
      significantly associated with age, gender and body area. CONCLUSION: Our results
      indicate that XPC is associated with BCC and further studies are warranted to
      determine if the XPC-BCC interaction is specific to just one cancer cell type and
      to investigate potential mechanisms.

PMID- 25600528
TI  - Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor
      HUHS015 using sodium salt.
AB  - Prostate cancer antigen (PCA)-1/AlkB homologue 3 (ALKBH3) has been identified as
      a clinically significant factor and siRNA of PCA-1 inhibits DU145 proliferation
      both in vitro and in vivo. HUHS015 ( 1: ), a previous reported PCA-1 small
      molecule inhibitor, was also effective without any obvious side-effects or
      toxicity. The potency of HUHS015, however, is not satisfying. We thought the
      reason is poor solubility of HUHS015 because insoluble material remained at the
      injection site after subcutaneous administration. To improve this inhibitor's
      solubility, we prepared various salts of HUHS015 and examined their solubility,
      which resulted in the selection of HUHS015 sodium salt ( 2: ) for further studies
      in vivo. Next, we compared the pharmacokinetics of 1: and 2: via several
      administration routes. We observed significant improvements in the
      pharmacokinetic parameters. For example, subcutaneous administration of 2:
      increased the area under the curve (AUC)0-24 by 8-fold compared to 1 and
      increased the suppressive effect on the proliferation of DU145 cells in a
      xenograft model. 

PMID- 25600529
TI  - Technological improvements for the treatment of obstructed defecation syndrome.
AB  - BACKGROUND/AIM: Standard stapled transanal rectal resection (STARR) with two PPH
      01TM poses some questions regarding the completeness of prolapse resection in
      patients with obstructed defecation syndrome (ODS) since 20% to 30% of patients
      have persistent rectocele or rectal intussusception that may impair the
      physiological recovery of rectal sensitivity. New high-volume (HV) devices, such
      as CPH34 HVTM and CPH36 SMSTM, allow for wider prolapsectomy to be performed and
      we herein assessed the possibility and safety of a STARR mono-stapler. MATERIALS
      AND METHODS: On May 30th-31st 2011, 13 pigs were selected to undergo standard
      STARR with two PPH-01TM (n=2) or STARR mono-stapler with one CPH34 HVTM (n=11) at
      the Experimental Center of Vila do Conde (Portugal); another set of 13 pigs was
      selected on January 14th-17th 2014 to undergo standard STARR (n=2) or STARR mono
      stapler by means of one CPH36 SMSTM (n=11). The length, height, square surface,
      and volume of resected specimens were intra-operatively assessed. Pigs were
      monitored for three days before undergoing transrectal sonography and autopsy to
      check for locoregional complications. RESULTS: CPH36 SMSTM STARR mono-stapler
      achieved 57% higher volume of prolapsectomy compared to Standard STARR (p=0.008);
      moreover, surface measures of the specimens of CPH36 SMSTM STARR mono-stapler
      were significantly higher (length, p=0.003; height, p=0.004; square surface,
      p=0.002) compared to CPH34 HVTM STARR mono-stapler, with a 97.8% increase of
      prolapsectomy (p<0.001). No intra- or early postoperative complications occurred.
      Transrectal sonography and autopsy detected: two (50%) small intra-parietal and
      two (50%) extra-rectal haematomata after Standard STARR; five small intraparietal
      (45.5%) and one (9%) extra-rectal haematoma after CPH34 HVTM STARR mono-stapler;
      three (27.2%) small intraparietal and (27.2%) extra-rectal haematomata after
      CPH36 SMSTM STARR mono-stapler. CONCLUSION: CPH36 SMSTM STARR mono-stapler is
      quite feasible both from the technological and safety standpoint; most
      importantly, the higher volume of prolapsectomy achievable with CPH36 SMSTM
      compared to standard STARR with two PPH-01TM might reduce the risk of
      residual/recurrent prolapse and further improve the clinical efficacy of the
      STARR procedure.

PMID- 25600530
TI  - Paraoxonase1 192 (PON1 192) gene polymorphism and serum paraoxonase activity in
      panic disorder patients.
AB  - BACKGROUND/AIM: Reactive oxygen species (ROS) are involved in the development of
      certain neuropsychiatric disorders. Paraoxonase 1 (PON1) activity has been
      suggested to be adversely related to oxidative stress in plasma. The purpose of
      the present study was to demonstrate the relationship between serum PON1 activity
      and PON1 192 polymorphism in panic disorder (PD). MATERIALS AND METHODS: Fourty
      two patients with PD and 46 healthy controls were included in this study. PON1
      192 genotypes were determined by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) analysis. PON1 activity was measured by
      spectrophotometric assay of p-nitrophenol production following the addition of
      paraoxon. RESULTS: PON1 192 AA genotype and A allele in PD were significantly
      higher than in the control group, whereas the B allele was found to be
      significantly higher in the control group. Patients with panic disorder have
      lower PON1 activity than the control group. CONCLUSION: The PON1 192 AA genotype
      may increase the risk of PD depending on lipid peroxidation.

PMID- 25600531
TI  - The healing effect of four different silver complexes on full-thickness skin
      burns in a rat model.
AB  - AIM: This study was carried-out to investigate the effect of four different
      silver substances (S1, S2, S3, and S4) on burn wound healing in a rat model.
      MATERIALS AND METHODS: One hundred and eighty Wistar rats were used. Animals were
      randomized into six groups to receive no treatment (CG, control group), and local
      application of the solvent of silver substances (SG, solvent group), as well as
      of the four silver substances (EG1-EG4 groups for substances S1-S4,
      respectively). On days 0, 3, 6, 12, 21, and 31 following burn wound infliction,
      the size and healing progress of each wound were recorded and evaluated by means
      of clinical evaluation, planimetry and histological examination. RESULTS:
      According to our findings lower infection rates, as well as significantly
      accelerated wound healing and faster re-epithelialization were recorded in EG1,
      EG2, and EG4 compared to the other groups. DISCUSSION: The use of S1, S2, and S4
      substances proved to be an effective treatment of burn wounds that ensured better
      outcomes compared to the control and solvent groups, as well as with the use of
      S3 substance. Nevertheless, they failed to produce short-term healing of the full
      thickness burn. Further research is required to examine the possibility of
      speeding the treatment of full-thickness burns by these complexes in order to
      reduce healing time to acceptable limits and prevent the need for surgery.

PMID- 25600532
TI  - Comparison between single PCR and nested PCR in detection of human papilloma
      viruses in paraffin-embedded OSCC and fresh oral mucosa.
AB  - BACKGROUND: Infection with human papilloma virus (HPV) has been implicated as one
      of the risk factors for the development of oropharyngeal cancer. Many different
      HPV tests exist, and information regarding their specific technical, analytical,
      and clinical properties is increasing. AIM: This study aimed to compare the level
      of detection of HPV using two reliable polymerase chain reaction (PCR) methods,
      nested PCR (NPCR) and single PCR (SPCR), in archival paraffin-embedded oral
      squamous cell carcinoma (OSCC) samples and fresh oral mucosa specimens. MATERIALS
      AND METHODS: The presence of HPV genome in two groups of tissue samples was
      analyzed: (i) 57 paraffin-embedded OSCC samples from Sudan and (ii) eight healthy
      fresh oral mucosal samples from Swedish volunteers. The specimens were tested by
      SPCR with primer pair MY9/MY11 and NPCR using GP5+/GP6+ primer sets. RESULTS:
      Eighteen (32%) out of the 57 paraffin-embedded OSCC samples, and five (62%) out
      of the eight fresh clinically healthy samples were found to be HPV-positive with
      NPCR. With SPCR, four (7%) out of the paraffin-embedded OSCC samples were HPV
      positive. A statistically significant difference between HPV-positive and 
      negative samples was found when comparing NPCR and SPCR in OSCC and fresh oral
      mucosa (p<0.0001). The comparative test between SPCR and NPCR showed 100%
      sensitivity and 69% specificity for OSCC. CONCLUSION: The use of the GP5+/GP6+
      nested PCR increased the positivity rate, efficiency rate and sensitivity of HPV
      detection in oral samples significantly and should be considered as the method of
      choice.

PMID- 25600533
TI  - Lack of association between MIF gene -173G>C polymorphism with multiple
      sclerosis.
AB  - AIM: The aim of the present study was to investigate a possible association
      between the MIF -173G>C polymorphism and MS in Turkish patients. MATERIALS AND
      METHODS: The study included 153 MS-patients and 210 controls. Genomic DNA was
      isolated and genotyped using PCR-RFLP assay for the MIF -173G>C promoter
      polymorphism (rs755622). RESULTS: There was no statistically significant
      difference in allele and genotype frequencies between MS-patients and controls
      (p=0.227 and p=0.157, respectively). Accordingly, no association was observed
      when the patients were compared against controls in terms of GG versus GC+CC
      genotypes and GG+GC versus CC genotypes (p=0.324 and p=0.179, respectively).
      Also, there was no statistically significant association between MIF-173G>C
      polymorphism and clinical and demographic characteristics of MS-patients.
      Conlusion: The results of the present study suggest no relation between MS
      susceptibility and MIF gene - 173G>C polymorphism in the examined Turkish
      population.

PMID- 25600534
TI  - Genotoxic effects of prenatal exposure to levetiracetam during pregnancy on rat
      offsprings.
AB  - Levetiracetam is a new-generation antiepileptic drug initially approved as an
      adjunctive treatment for patients with refractory partial seizures and is now
      also used as a monotherapy. The aim of this study was to evaluate the genotoxic
      effects of levetiracetam exposure during pregnancy on rat offsprings. In this
      study, we used the newborn pups of rats exposed to levetiracetam during
      pregnancy. Thirty Sprague-Dawley rats were divided into three groups. The mother
      rats of groups 1 and 2 were treated with different doses of levetiracetam (25
      mg/kg/d and 50 mg/kg/d) from gestational days 1 to 18 during pregnancy. Group 3
      (control group) was not treated with any drug. In vivo sister chromatid exchange
      (SCE) induction and in vivo micronucleus formation were assessed. Bone marrow
      from rat pups were used for investigation. As a result of this study,
      levetiracetam exposure did not alter SCE frequencies or the mean of number of
      micronuclei in the prenatal period (p>0.05). Levetiracetam did not cause
      miscarriage during pregnancy in mother rats. The present study highlighted fetal
      safety after prenatal exposure to levetiracetam. 

PMID- 25600535
TI  - Demethoxycurcumin alters gene expression associated with DNA damage, cell cycle
      and apoptosis in human lung cancer NCI-H460 cells in vitro.
AB  - Lung cancer is the leading cause of cancer-related deaths and new lung cancer
      cases are continuously emerging around the globe; however, treatment of lung
      cancer remains unsatisfactory. Demethoxycurcumin (DMC) has been shown to exert
      cytotoxic effects in human cancer cells via induction of apoptosis. However, the
      effects of DMC on genetic mechanisms associated with these actions have not been
      yet elucidated. Human lung cancer NCI-H460 cells were incubated with or without
      35 MUM of DMC for 24 h and total RNA was extracted for cDNA synthesis labeling
      and microarray hybridization, followed by fluor-labeled cDNA hybridization on
      chip. Expression Console software with default Robust Multichip Analysis (RMA)
      parameters were used for detecting and quantitating the localized concentrations
      of fluorescent molecules. The GeneGo software was used for investigating key
      genes involved and their possible interaction pathways. Genes associated with DNA
      damage and repair, cell-cycle check point and apoptosis could be altered by DMC;
      in particular, 144 genes were found up-regulated and 179 genes down-regulated in
      NCI-H460 cells after exposure to DMC. In general, DMC-altered genes may offer
      information to understand the cytotoxic mechanism of this agent at the genetic
      level since gene alterations can be useful biomarkers or targets for the
      diagnosis and treatment of human lung cancer in the future. 

PMID- 25600536
TI  - Microscopic assessment of degenerated intervertebral disc: clinical implications
      and possible therapeutic challenge.
AB  - AIM: To investigate a possible correlation between the histological and
      morphometric properties of herniated intervertebral disc, clinical and magnetic
      resonance imaging (MRI) characteristics of patients with lumbar disc degeneration
      (LDD). MATERIALS AND METHODS: Thirty six patients with LDD were clinically
      evaluated using Japanese Orthopaedic Association Score (JOAS), visual analogue
      scale (VAS) for pain in the lower back or in the pelvic limb; MRI-based
      classification according to Pfirrmann and Modic criteria. All patients underwent
      decompressive surgery and herniated intervertebral disc samples were
      histologically and morphometrically analyzed. Data obtained were statistically
      analyzed for bivariate and partial correlations. RESULTS: The mean area size of
      chondron clusters correlated with age, JOAS (r=-0.385, p=0.032, tau=-0.279, rho=
      0.380), Pfirrmann (r=0.505, p=0.002, tau=0.289, rho=0.365) and Modic (r=0.500,
      p=0.002, tau=0.331, rho=0.419) grading. There was a strong correlation between
      maximum area size of chondrons and JOAS (r=-0.427, p=0.009, tau=-0.299, rho=
      0.430), Pfirrmann changes (r=0.432, p=0.008, tau=0.309, rho=0.388) and Modic
      endplate changes (r=0.444, p=0.007, tau=0.343, rho=0.434). JOAS correlated with
      both MRI classifications used for LDD. CONCLUSION: The intervertebral disc cells
      tend to aggregate in clusters and the size of the chondrons from LDD correlated
      with JOAS, Pfirrmann and Modic. JOAS correlates with the imagistic evaluation
      systems Pfirrmann and Modic.

PMID- 25600537
TI  - Evaluation of paraoxonase 1 polymorphisms in patients with bipolar disorder.
AB  - AIM: Bipolar disorder (BD) has a complex genetic etiology, with multiple
      unidentified genes and environmental factors playing important roles in its
      pathogenesis. A growing body of evidence suggests that reactive oxygen species
      (ROS) may be crucially involved in the pathogenesis of psychiatric diseases,
      including BD. The association between paraoxonase 1 (PON1), an important
      antioxidant enzyme, and development of BD has been scarcely investigated. We thus
      attempted to examine genetic variants in the PON1 gene, a putative BD
      susceptibility gene, in patients with bipolar disease and their first-degree
      relatives. MATERIALS AND METHODS: The study population consisted of 292 healthy
      individuals, 199 patients with BD, and 280 unaffected first-degree relatives of
      the patients. Genotyping of PON1 L55M and Q192R polymorphisms was performed by
      polymerase chain reaction and restriction enzyme digestion. RESULTS: Patients
      mostly shared the same PON1 genotypes with their first-degree relatives. The
      frequency of MM genotype of PON1 L55M polymorphism was lower and that of LM
      genotype was higher in patients and relatives than healthy controls. PON1 enzyme
      activities did not differ between patient, relative and healthy control groups
      but were influenced by PON1 genotype. CONCLUSION: Our findings indicate an
      association between the genetic variants of PON1 and BD. The PON1 L55M MM
      genotype seems to be protective against the development of BD.

PMID- 25600538
TI  - Efficacy and side-effects of a semi-individualized Chinese herb mixture "Tiao
      Geng Tang" for menopausal syndrome in China.
AB  - BACKGROUND: Chinese herbal medicine is an alternative therapy for menopausal
      problems and is widely practiced in China and many other Asian countries.
      However, efficacies and side-effects are rarely assessed according to the
      standards of evidence-based medicine. PATIENTS AND METHODS: This is a prospective
      observatory study following efficacy and side-effects of a semi-individualized
      Chinese herbal mixture "Tiao Geng Tang (TGT)" in 30 patients for 3 months.
      Another group of 30 patients receiving hormone therapy with tibolone was included
      as a positive comparison. Common questionnaire-based measuring instruments were:
      modified Kupperman index, menopause rating scale, life quality and Chinese
      medical symptom scale (CMSS). Follicle-stimulating hormone (FSH), luteinizing
      hormone (LH) and estradiol (E2) were determined before and three months after the
      treatments. RESULTS: Significant improvement was seen in overall scores of all
      the four measurements in both groups. For some symptoms, including dry mouth,
      tinnitus, poor appetite and constipation, TGT was more effective than tibolone.
      For psychosocial and sexual sub-scales of life quality, tibolone has a slightly
      higher remedy rate than TGT. TGT lowered FSH and LH significantly, as tibolone
      did, but elevated E2 significantly less than tibolone. Various adverse events,
      including body weight increase, abdomen discomfort, nausea/vomiting, emotional
      instability, pressure in breasts and dizziness, were reported by patients treated
      with tibolone, whereas only diarrhea was observed in two patients treated with
      TGT. CONCLUSION: TGT alleviates menopausal symptoms with similar efficacy as
      tibolone but has fewer side effects.

PMID- 25600539
TI  - Serum and Urinary Neutrophil Gelatinase-associated Lipocalin Monitoring in Normal
      Pregnancy Versus Pregnancies Complicated by Pre-eclampsia.
AB  - AIM: Pre-eclampsia is a syndrome characterized by endothelium dysfunction,
      systemic inflammation, and kidney injury that could be associated with increased
      levels of neutrophil gelatinase-associated lipocalin (NGAL). We investigated
      whether serum and urinary NGAL may have a clinical value in defining the severity
      of pre-eclampsia. PATIENTS AND METHODS: This cross-sectional case-control study
      enrolled 18 women with pre-eclampsia matched for gestational age with 22
      uncomplicated pregnancies. We evaluated the correlation between NGAL levels and
      blood pressure and 24-hour proteinuria values by linear regression. RESULTS:
      Linear regression disclosed a positive and significant correlation between
      urinary NGAL and 24-hour proteinuria. Serum NGAL appeared to be higher, but not
      significantly different, in severe pre-eclampsia. CONCLUSION: These preliminary
      data indicate that NGAL may correlate with an inflammatory renal involvement in
      severe pre-eclampsia. Further studies would be useful to better estimate the
      clinical value of an NGAL increase for evaluating the possibility of delivery
      induction.

PMID- 25600540
TI  - Risk assessment in patients with acute alcohol intoxication.
AB  - AIM: Patients with acute alcohol intoxication present a serious and still growing
      problem for pre- and intra-hospital emergency services. Data on the clinical risk
      assessment of alcohol-intoxicated patients are sparse. The aim of the present
      work was, therefore, to collect and assess relevant risk parameters. MATERIALS
      AND METHODS: At the Mannheim University Hospital, the medical records of 844
      alcohol-intoxicated Emergency Department patients were retrospectively studied
      and evaluated. RESULTS: The patients with alcohol intoxications were
      predominantly males with an average age of 45 years. Mean blood alcohol
      concentration was 0.28%. The rate of haemodynamic, respiratory or metabolic
      complications in these patients was low. In 43% of cases, there was moderately to
      severely impaired consciousness. About half of the patients were treated on an
      outpatient basis. CONCLUSION: Our data demonstrate a low clinical risk for
      alcohol-intoxicated patients. Nevertheless, it is necessary to provide a defined
      monitoring standard in order to also be prepared for the few potential
      complications of alcohol intoxication and the possible differential diagnoses of
      impaired consciousness.

PMID- 25600541
TI  - The relationship between catechol-O-methyltransferase gene Val158Met (COMT)
      polymorphism and premorbid cannabis use in Turkish male patients with
      schizophrenia.
AB  - BACKGROUND/AIM: One of the risk factors for increasing psychotic disorders is the
      use of cannabis. It has been shown that the inactivation of dopamine and other
      catecholamines causes a common polymorphism generating substantial variations in
      COMT enzyme activity. We aimed to understand the role of cannabis in the etiology
      of schizophrenia with and without pre-morbid usage. PATIENTS AND METHODS: The
      study group consisted of 80 male patients and genotyping of COMT enzyme Val158Met
      gene polymorphisms were detected by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: It was found that the Val/Val
      genotype is significantly higher in patients with premorbid cannabis use (88.9%)
      compared to patients without pre-morbid cannabis use (68.4%). Also, the mean
      total positive and negative syndrome scale (PANSS) score seen in the Val/Val
      genotype group is significantly higher than the scores of the patients with the
      Met allele. CONCLUSION: The findings from this study confirm the association
      between COMT Val158 Met polymorphism and pre-morbid cannabis use in causing
      schizophrenia.

PMID- 25600542
TI  - Different impact of anti-retroviral regimen containing protease inhibitors on
      development of HIV-related Kaposi sarcoma.
AB  - BACKGROUND: The incidence of Kaposi's sarcoma (KS), an AIDS-related malignancy,
      has dramatically decreased in the Highly Active Anti-retroviral Therapy (HAART)
      era. However, KS remains the second most frequent tumor in HIV-infected patients
      worldwide and has become the most common cancer in the sub-Saharan Africa.
      Experimental studies have demonstrated a direct anti-neoplastic effect of HAART,
      and overall of protease inhibitors (PIs), on KS. CASE REPORT: We describe five
      cases of KS in HIV-infected patients on HAART regimen, containing PIs as
      atazanavir/r (ATV/r), darunavir/r (DRV/r), lopinavir/r (LPV/r) and fosamprenavir
      (fAMP/r). CONCLUSION: Clinical and experimental observations support the
      hypothesis that PIs may play an important role in prevention and treatment of KS.
      In our study, the treatment with PIs of recent generation was not protective
      against the development of KS. Therefore, it could be necessary to re-evaluate
      the therapeutic effects of PIs and their role in the development and treatment of
      KS in HIV-infected patients.

PMID- 25600543
TI  - Interferon gamma release assays and tubercolin skin test performance in different
      settings of HIV immunodeficiency.
AB  - BACKGROUND/AIM: HIV infection is a risk factor for re-activation of latent
      tubercolosis infection (LTBI). In recent years new blood tests for the detection
      of TB infection have been developed: Quantiferon TB Gold in Tube and TSPOT TB,
      which are interferon-gamma releasing assays (IGRAs), have improved the
      identification of LTBI. In our study we have compared IGRAs and TST in HIV
      positive patients with different settings of immunodeficiency. PATIENTS AND
      METHODS: 98 consecutive HIV patients were recruited. They underwent a blood draw,
      a chest radiography and a tuberculin skin test. The HIV infection setting was
      detected and IGRAs were carried-out. Five patients showed a complete
      correspondence of TST, TSPOT-TB and QFT-IT. Discordant results were observed in
      patients testing positive to IGRAs but negative to TST. Only 2 patients showed
      positive TST and negative IGRAs. CONCLUSION: Our study showed a poor concordance
      between tuberculin skin test and IGRAs, mainly in patients with a low CD4 cell
      count.

PMID- 25600544
TI  - Acetylsalicylic acid resistance after renal transplantation.
AB  - BACKGROUND: Cardiovascular diseases are a leading cause of mortality after kidney
      transplantation. According to guidelines, acetylsalicylic acid (ASA) must be
      given as preventive antiplatelet therapy, but resistance to this drug is also
      well-known. PATIENTS AND METHODS: A total of 214 renal transplant patients were
      included in our study and took 100 mg of ASA q.d. Aggregometry was performed to
      determine resistance. Twenty-four variables were examined using logistic
      regression analysis as possible causes of resistance. RESULTS: ASA resistance was
      observed in 40.18% of the patients. Resistance reduced concomitant statin therapy
      and significantly increased simultaneous cyclosporine therapy. CONCLUSION: Our
      study assessed the post-transplant ASA resistance in a large population.
      Clarification of this matter is crutial, since one of the major preventive
      pharmacological therapies of cardiovascular mortality is not effective in a
      significant number of patients.

PMID- 25600545
TI  - Octyl-2-cyanoacrylate adhesive for skin closure: eight years experience.
AB  - Cyanoacrylate skin adhesive is increasingly used to ensure and stabilize wound
      closures. One of the documented favorable effects of these glues is to limit the
      risk of a surgical site infection by physically isolating the wound. PATIENTS AND
      METHODS: From January 2005 to January 2013, 900 patients requiring surgical
      treatment in the Structure of Plastic Surgery of the University of Sienna were
      enrolled for the study and divided in two groups; 450 patients treated with glue
      versus 450 controls. RESULTS: The cohort of patients treated with glue had lower
      incidence of wound infection and wound dehiscence. Approximately 375 work-hours
      were economized. CONCLUSION: Octyl-2-cyanoacrylate is a valuable aid for ensuring
      the success of surgery by reducing surgical site infections. The use of octyl-2
      cyanoacrylate is easy, guarantying a major superficial protection without
      relevant contraindications and with evident saving of time and resources.

PMID- 25600546
TI  - Flow cytometric assessment of P-glycoprotein and multidrug resistance-associated
      protein activity and expression in canine lymphoma.
AB  - AIM: To investigate the activity and expression of P-glycoprotein (P-gp) and
      multidrug resistance-associated proteins (MRPs) in biopsy samples from lymph
      nodes of 22 dogs at the time of lymphoma diagnosis. MATERIALS AND METHODS:
      Protein activity and expression were investigated by flow cytometry. Expression
      was assessed with monoclonal antibodies (C494 for P-gp and MRPm6 for MRP1). P-gp
      activity was determined by rhodamine 123 (Rho 123) efflux inhibited by verapamil
      and MRP by 5(6) carboxyfluorescein diacetate (CFDA) efflux inhibited by
      probenecid. Cell lineage was determined based on the expression of CD79alpha,
      CD21, CD3, CD4 and CD8. RESULTS: P-gp and MRP1 were expressed in all samples.
      Relative activity was low for both transporters and no correlation was found
      between transporter activity and expression. The majority of lymphomas were of B
      cell origin. CONCLUSION: Low transporter activity and lack of correlation with
      expression suggest that spontaneous up-regulation of P-gp or MRP is not a common
      phenomenon in canine lymphoma.

PMID- 25600547
TI  - Awareness of prenatal screening for fetal aneuploidy among pregnant women in
      Greece.
AB  - AIM: To estimate the level of awareness of prenatal screening (PS) and explore
      the underlying demographic, lifestyle and medical history parameters of Greek and
      non-Greek pregnant women undergoing prenatal diagnosis. PATIENTS AND METHODS: A
      structured questionnaire was answered by 354 women at the time of receiving the
      results of invasive prenatal testing. Summary statistics and multiple logistic
      regression analyses were performed. RESULTS: Adequate knowledge of the
      effectiveness of PS tests was reported by 50.8% of women. Popular press reading
      was associated with more than 2-fold higher level of awareness [odds ratio
      (OR)=0.51, p=0.0004]. Inadequate awareness was recorded among pregnant women of
      non-Greek nationality (OR=2.07, p=0.04), as well as among those also unaware of
      the effects of smoking during pregnancy (OR=2.39, p=0.004). CONCLUSION: Pre
      gestational prenatal counseling is essential in order to improve knowledge and
      attitudes of women towards PS and reduce the health gap between different
      cultural and social groups.

PMID- 25600548
TI  - Altered IL-2, IL-6 and IL-8 serum levels in schizophrenia patients with tardive
      dyskinesia.
AB  - Immune deregulation has been postulated to be one of the mechanisms underlying
      the pathogenesis of tardive dyskinesia (TD). We hypothesized that interleukins
      would have a link with TD in schizophrenia patients. In this study, the serum IL
      2, IL-6 and IL-8 levels were examined by enzyme-linked immunosorbent assay
      (ELISA) in schizophrenia patients with TD (n=48) and without TD (n=45), and
      healthy controls (n=44). The psychopathological symptoms of schizophrenia were
      assessed by the Positive and Negative Syndrome Scale (PANSS). The severity of TD
      was evaluated using Abnormal Involuntary Movement Scale (AIMS). The results
      showed that serum IL-2, IL-6 and IL-8 levels were significantly different among
      schizophrenia patients with TD and without TD and normal controls. Moreover, IL-2
      level was significantly correlated with PANSS positive subscale and general
      subscale in patients with TD and without TD. In addition, IL-2 level was
      positively correlated with AIMS score in TD patients. The results supported that
      immune disturbance is related to the schizophrenia patients, especially to the
      patients with TD and ILs might play an important role in the pathophysiology of
      schizophrenia patients with TD. 

PMID- 25600549
TI  - Altered cortical maturation in adolescent cannabis users with and without
      schizophrenia.
AB  - During late adolescence, progressive cortical thinning occurs in heteromodal
      association cortex (HASC) that is thought to subserve cognitive development.
      However, the impact of cannabis use disorder (CUD) upon cortical gray matter
      development in both healthy adolescents and adolescents with early-onset
      schizophrenia (EOS) is unclear. T1-weighted magnetic resonance images were
      acquired from 79 adolescents at baseline and after an 18-month follow-up: 17 with
      EOS, 17 with CUD, 11 with EOS+CUD, and 34 healthy controls (HC). Mean age at
      baseline was 16.4years (CUD+) and 17.0years (CUD-). Using FreeSurfer, measures of
      cortical thickness for ROIs within HASC were obtained. A 2 (EOS versus no EOS)*2
      (CUD versus no CUD) multivariate analysis of covariance was applied to change
      scores from baseline to follow-up to test for main effects of EOS and CUD and an
      interaction effect. After adjusting for covariates, a significant main effect of
      CUD was observed. Adolescents with CUD showed an attenuated loss of cortical
      thickness in the left and right supramarginal, left and right inferior parietal,
      right pars triangularis, left pars opercularis, left superior frontal, and left
      superior temporal regions compared to non-using subjects. Stepwise linear
      regression analysis indicated that greater cumulative cannabis exposure predicted
      greater cortical thickness in both the left (p=.008) and right (p=.04) superior
      frontal gyri at study endpoint after adjusting for baseline cortical thickness
      for the entire sample. These preliminary longitudinal data demonstrate an
      atypical pattern of cortical development in HASC in adolescents with CUD relative
      to non-using subjects, across diagnostic groups. Additional studies are needed to
      replicate these data and to clarify the clinical significance of these findings. 

PMID- 25600550
TI  - N-Methyl-d-aspartate receptor autoantibodies in schizophrenia and affective
      disorders.

PMID- 25600551
TI  - The efficacy of 90cm-long peritoneal shunt catheters in newborns and infants.
AB  - BACKGROUND: Ventriculoperitoneal (VP) shunt is one of the options for the
      treatment of hydrocephalus. The aim of this study is to describe the efficacy and
      safety of a 90cm-long peritoneal catheter in newborns and infants treated for
      hydrocephalus. We analyzed the incidence of distal-related complications and the
      need of successive surgeries for malfunction or for lengthening of the peritoneal
      catheter. METHODS: We reviewed medical records of neonates and infants treated
      with a VP shunt using a 90cm-long peritoneal catheter. Function and integrity of
      shunts were assessed through abdominal echographic studies, skull, neck, chest
      and abdomen X-rays. We compared shunt revision rates due to distal complications
      and insufficient length of the peritoneal catheter in the study group with an
      historical control group composed by newborns and infants treated with a standard
      VP shunt at our Institution during the last twenty years. RESULTS: Three neonates
      and 3 infants were treated with the insertion of the 90cm-long distal catheter
      into the peritoneal cavity for its total length. The mean follow-up was 7.6
      years. As compared to controls, in the study group the revision rate for distal
      complications was not significantly increased (P=0.33), whereas revision
      surgeries due to insufficient peritoneal catheter length were significantly
      reduced (P=0.04). CONCLUSIONS: This study demonstrates for the first time that
      the use of 90cm-long peritoneal catheters in neonates and infants is a safe and
      effective procedure. It does not increase the incidence of abdominal
      complications, avoiding the need of revision for insufficient length of the
      peritoneal catheter.

PMID- 25600552
TI  - Role of nitric oxide and mechanisms involved in cerebral injury after
      subarachnoid hemorrhage: is nitric oxide a possible answer to cerebral vasospasm?
AB  - Cerebral vasospasm represents the most critical event that could occur after
      subarachnoid hemorrhage (SAH). Therapy is only partially effective because
      cerebral arterial constriction is not fully understood yet. One of the most
      important biological messenger associated to SAH is nitric oxide (NO), that is
      considered local regulator of cerebral blood flow. Different nitric oxide
      synthase (NOS) forms play a role in different biological processes, one of which
      is to link neuronal activity to blood flow in cerebral cortex. We performed a
      reassessment of the literature to summarize the role of NO as the main
      inflammatory pathway activated after SAH to clarify its importance for treatment
      of vasospasm. 

PMID- 25600553
TI  - Prognostic factors for temporal lobe epilepsy surgery in a tertiary center.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) represents the most common type of
      partial epilepsy. Early age of onset, a history of febrile convulsions,
      epileptiform discharges on electroencephalography, duration of epilepsy, number
      of generalized seizures and severity of psychiatric disorders are possible
      prognostic factors in patients with mesial temporal sclerosis. The aim of this
      study is to review the findings of clinical research, semiotic, psychological,
      electrophysiological and neuroradiological, and to relate these findings with the
      prognosis of patients with TLE who underwent anteromedial temporal lobectomy
      (ATL). METHODS: Of 1214 patients evaluated for surgery in the epilepsy Center of
      the Sao Jose do Rio Preto Faculty of Medicine (Faculdade de Medicina de Sao Jose
      do Rio Preto - FAMERP), a tertiary Brazilian epilepsy center, 459 underwent ATL
      for TLE. Exams and clinical data were analyzed and compared with Engel
      classification for outcome. RESULTS: Of all the items analyzed, the MRI showed a
      greater influence on the outcome of patients and for clinical evaluation and
      pathological antecedents, age at surgery, the epilepsy duration, seizure
      frequency, mesial temporal sclerosis, dysplasia, perinatal insults, vascular
      insults, a family history of epilepsy, febrile seizures, neuropsychological
      abnormalities and presence of generalized tonic-clonic seizure has a statistical
      significance. CONCLUSIONS: In order to identify the most appropriate candidates
      for ATL, it is very important to consider the prognostic factors associated with
      favorable for counseling patients in daily practice.

PMID- 25600554
TI  - Image guided surgery versus conventional brain tumor and craniotomy localization.
AB  - BACKGROUND: Accurate brain lesion and craniotomy localization is an essential
      step in neurosurgical procedures. Image guided techniques transfer the
      information of neuroimaging about brain lesion localization to the patient. A
      critical view is necessary to find out how safe and reliable it is to transfer
      this information to the patient's head without using image guided systems. The
      aim of this study was to investigate the value of image guided brain lesion and
      craniotomy localization compared to conventional methods. METHODS: A new
      developed test was performed with 10 neurosurgeons from different clinics. The
      first task was to perform the conventional tumor localization, planning of
      craniotomy and skin incision using the MRI dataset of a patient with a left
      temporal brain tumor. Second, the neurosurgeons were asked to plan the craniotomy
      and skin incision using MRI based 3D visualization with the exact localization of
      the segmented brain tumor. Both plans of each neurosurgeon were compared and
      analyzed according to the calculated brain tumor localization, location, shape
      and size of craniotomy. RESULTS: All neurosurgeons changed the craniotomy
      localization and skin incision in the second part of the task using the image
      guided tumor visualization. The mean error (+/-standard deviation) of tumor
      localization of the conventional planning was 11.45+/-5.09 mm in the anterior
      posterior (AP) and 12+/-7.91 mm in the superior-inferior (SI) direction. The mean
      error of the craniotomy localization using conventional planning was 10.18+/-6.09
      mm in the AP and 10.75+/-8.18 mm in the SI direction. The craniotomy size was
      significantly larger using conventional planning of the craniotomy (P=0.035).
      CONCLUSIONS: Conventional brain tumor and craniotomy localization leads more
      frequently to errors and oversized craniotomy. Image guided surgery can reduce
      these errors and increase the safety and orientation for preoperative planning.

PMID- 25600555
TI  - Post-stereotactic radiosurgery brain metastases: a review.
AB  - Stereotactic radiosurgery (SR) is a standard therapy for brain metastases.
      Radiation necrosis (RN) of the brain is a syndrome of brain coagulative and
      fibrinoid necrosis and cortical irritation that occurs following radiotherapy. RN
      following SR peaks in a delayed fashion at 9-12 months postprocedure. Vasogenic
      cerebral edema secondary to necrosis occurs and can affect surrounding brain
      function. No definitive non-invasive diagnostic study exists to differentiate
      post-SR RN from recurrent metastatic tumor. Magnetic resonance (MR) imaging, MR
      spectroscopy, positron emission tomography, and perfusion-weighted MR imaging
      have been used to evaluate RN and are discussed. Treatment options for post-SR
      brain metastases include observation, corticosteroids, pentoxifylline and vitamin
      E, bevacizumab, radiotherapy, laser-interstitial thermal therapy, and surgical
      resection. 

PMID- 25600557
TI  - Hepatitis C virus infection and risk factors in the general population: a large
      community-based study in eastern China, 2011-2012.
AB  - Limited information is available on the prevalence of hepatitis C virus (HCV) in
      the general population in China. A community-based epidemiological study was
      conducted in three counties in eastern China. A total of 149 175 individuals were
      investigated in 60 communities in three counties in Jiangsu province, eastern
      China, of whom 1175 subjects [0.79%, 95% confidence interval (CI) 0.74-0.83] were
      HCV antibody positive. The prevalence was low in children (0.09%, 95% CI 0.04
      0.17), but increased progressively from adolescents (0.20%, 95% CI 0.15-0.28) to
      adults aged ?21 years (95% CI 0.15-1.64). Women had a higher prevalence of HCV
      infection than men in most age groups. In a multilevel regression analysis, age,
      sex, education, occupation, blood transfusion [odds ratio (OR) 2.91, 95% CI 1.09
      5.37], invasive testing (OR 1.28, 95% CI 1.14-1.61), and dental therapy (OR 2.27,
      95% CI 1.41-3.42) were associated with HCV infection. In conclusion, although the
      prevalence of HCV in this population was lower than reported from national
      levels, the total reservoir of infection is significant and warrants public
      health measures, such as health education to limit the magnitude of the problem. 

PMID- 25600559
TI  - Clinical comparison between wall defects surgery using conventional and low
      adhesion mesh materials Preliminary results.
AB  - PURPOSE: The use of prosthetic materials for hernia repair has become a standard
      procedure. Still the optimal material has not yet been found. Primitive hernia
      with loss of substance and big incisional hernia repair requires a prosthetic
      material which not induce, especially in the area of visceral peritoneal contact,
      chronic inflammation and fibrosis. The aim of this study is to clinically compare
      two different mesh materials: uncoated monofilament polypropylene and
      polypropylene- polyurethane double surface mesh. METHODS: Forty eight primitive
      hernia and incisional hernia affected patients were included in the study. They
      were randomly allocated in two groups. In each group a different type of mesh was
      utilized, respectively uncoated monofilament polypropylene mesh and polypropylene
      polyurethane double surface synthetic mesh. Lichtenstein and Rives surgical
      techniques were utilized. Intra-operative, early and late post-operative
      complications were clinically evaluated. RESULTS: Uncoated monofilament
      polypropylene meshes treated patients showed higher abdominal pain, inflammatory
      diseases and hernia recurrence incidence than polypropylene-polyurethane double
      surface meshes. Abdominal wall hypo-mobility, discomfort and atypical sensation
      were the same in the two groups of treated patients. CONCLUSIONS: Given the
      limited number of our patient's set, from our preliminary results is possible to
      assert that polypropylene-polyurethane double surface meshes have revealed
      superior bio-functional and bio-compatible efficacy.

PMID- 25600558
TI  - Origins of multicellular evolvability in snowflake yeast.
AB  - Complex life has arisen through a series of 'major transitions' in which
      collectives of formerly autonomous individuals evolve into a single, integrated
      organism. A key step in this process is the origin of higher-level evolvability,
      but little is known about how higher-level entities originate and gain the
      capacity to evolve as an individual. Here we report a single mutation that not
      only creates a new level of biological organization, but also potentiates higher
      level evolvability. Disrupting the transcription factor ACE2 in Saccharomyces
      cerevisiae prevents mother-daughter cell separation, generating multicellular
      'snowflake' yeast. Snowflake yeast develop through deterministic rules that
      produce geometrically defined clusters that preclude genetic conflict and display
      a high broad-sense heritability for multicellular traits; as a result they are
      preadapted to multicellular adaptation. This work demonstrates that simple
      microevolutionary changes can have profound macroevolutionary consequences, and
      suggests that the formation of clonally developing clusters may often be the
      first step to multicellularity. 

PMID- 25600560
TI  - CD74 expression and its therapeutic potential in thyroid carcinoma.
AB  - CD74, the invariant chain of major histocompatibility complex class II, is also a
      receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been
      associated with tumor progression and metastasis in hematologic and solid tumors.
      In this study, we found that 60 and 65% of papillary thyroid cancers were
      positive for CD74 and MIF immunohistochemical staining respectively. Anaplastic
      thyroid cancer was negative for MIF, but mostly positive for CD74 expression.
      Normal thyroid tissue and follicular adenomas were negative for CD74 expression.
      CD74 expression in papillary thyroid cancer was associated with larger tumor size
      (P=0.043), extrathyroidal invasion (P=0.021), advanced TNM stage (P=0.006), and
      higher MACIS score (P=0.026). No clinicopathological parameter was associated
      with MIF expression. Treatment with anti-CD74 antibody in thyroid cancer cells
      inhibited cell growth, colony formation, cell migration and invasion, and
      vascular endothelial growth factor secretion. In contrast, treatment with
      recombinant MIF induced an increase in cell invasion. Anti-CD74 treatment reduced
      AKT phosphorylation and stimulated AMPK activation. Our findings suggest that
      CD74 overexpression in thyroid cancer is associated with advanced tumor stage and
      may serve as a therapeutic target. 

PMID- 25600561
TI  - Comparison study of in vivo dose response to laser-driven versus conventional
      electron beam.
AB  - The long-term goal to integrate laser-based particle accelerators into
      radiotherapy clinics not only requires technological development of high
      intensity lasers and new techniques for beam detection and dose delivery, but
      also characterization of the biological consequences of this new particle beam
      quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe
      successful in vivo experiments with laser-driven electron pulses by utilization
      of a small tumour model on the mouse ear for the human squamous cell carcinoma
      model FaDu. The already established in vitro irradiation technology at the laser
      system JETI was further enhanced for 3D tumour irradiation in vivo in terms of
      beam transport, beam monitoring, dose delivery and dosimetry in order to
      precisely apply a prescribed dose to each tumour in full-scale radiobiological
      experiments. Tumour growth delay was determined after irradiation with doses of 3
      and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with
      continuous electron beams at a clinical linear accelerator in order to both
      validate the dedicated dosimetry employed for laser-accelerated JETI electrons
      and above all review the biological results. No significant difference in
      radiation-induced tumour growth delay was revealed for the two investigated
      electron beams. These data provide evidence that the ultra-high dose rate
      generated by laser acceleration does not impact the biological effectiveness of
      the particles.

PMID- 25600562
TI  - Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung
      cancer >=4 cm in size: an SEER-Medicare analysis.
AB  - BACKGROUND: The role of adjuvant chemotherapy for non-small-cell lung cancer
      (NSCLC) stage I patients with tumors size >=4 cm is not well established in the
      elderly. PATIENTS AND METHODS: We identified 3289 patients with stage I NSCLC
      (T2N0M0 and tumor size >=4 cm) who underwent lobectomy from the Surveillance,
      Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992
      to 2009. Overall survival and rates of serious adverse events (defined as those
      requiring admission to hospital) were compared between patients treated with
      resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation
      (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving
      each treatment were calculated and survival analyses were conducted using inverse
      probability weights based on the propensity score. RESULTS: Overall, 84% patients
      were treated with resection alone, 9% received platinum-based adjuvant
      chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy.
      Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95%
      confidence interval (CI) 0.68-0.98] was associated with improved survival
      compared with resection alone. Conversely, the use of PORT with or without
      adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse
      outcomes. Patients receiving adjuvant chemotherapy had more serious adverse
      events compared with those treated with resection alone, with neutropenia (odds
      ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference
      was observed in rates of fever, cytopenias, nausea, and renal dysfunction.
      CONCLUSIONS: Platinum-based adjuvant chemotherapy is associated with reduced
      mortality and increased serious adverse events in elderly patients with stage I
      NSCLC and tumor size >=4 cm.

PMID- 25600563
TI  - Contralateral biopsies in patients with testicular germ-cell tumour-nuisance or
      new sense?

PMID- 25600564
TI  - Reply to the letter to the editor 'Albumin to globulin ratio, a predictor or a
      misleader?' by Alkan et al.

PMID- 25600565
TI  - Association of PD-L1 expression on tumor-infiltrating mononuclear cells and
      overall survival in patients with urothelial carcinoma.
AB  - BACKGROUND: Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway
      negatively regulates T-cell-mediated responses. The prognostic impact of PD-L1
      expression needs to be defined in urothelial carcinoma (UC). PATIENTS AND
      METHODS: Formalin-fixed paraffin-embedded tumor samples from 160 patients with UC
      were retrieved. PD-L1 expression was evaluated by immunohistochemistry using a
      mouse monoclonal anti-PD-L1 antibody (405.9A11). PD-L1 positivity on tumor cell
      membrane was defined as >=5% of tumor cell membrane staining. The extent of tumor
      infiltrating mononuclear cells (TIMCs) as well as PD-L1 expression on TIMCs was
      scored from 0 to 4. A score of 2, 3, or 4 was considered PD-L1-positive. Clinico
      pathological variables were documented. The Cox regression model was used to
      assess the association of PD-L1 expression with overall survival (OS) in patients
      who developed metastases. RESULTS: TIMCs were present in 143 of the 160 patient
      samples. Out of 160 samples, 32 (20%) had positive PD-L1 expression in tumor cell
      membrane. Out of 143 samples with TIMCs, 58 (40%) had positive PD-L1 expression
      in TIMCs. Smoking history, prior BCG use and chromosome 9 loss did not correlate
      with PD-L1 expression in either tumor cell membrane or TIMCs. PD-L1 positivity
      was not different between non-invasive or invasive UC. In patients who developed
      metastases (M1) and were treated with systemic therapy (n = 100), PD-L1
      positivity on tumor cell membrane was seen in 14% of patients and did not
      correlate with OS (P = 0.45). Out of 89 M1 patients who had evaluable PD-L1 on
      TIMCs, PD-L1 expression was seen in 33% of patients and was significantly
      associated with longer OS on multivariate analysis (P = 0.0007). CONCLUSION: PD
      L1 is widely expressed in tumor cell membrane and TIMCs in UC. PD-L1 in tumor
      cells was not predictive of OS. However, positive PD-L1 expression in TIMCs was
      significantly associated with longer survival in those patients who developed
      metastases.

PMID- 25600566
TI  - Different adjuvant chemotherapy regimens in older breast cancer patients?

PMID- 25600567
TI  - Risk of subsequent in situ and invasive breast cancer in human epidermal growth
      factor receptor 2-positive ductal carcinoma in situ.
AB  - BACKGROUND: To assess the prognostic role of human epidermal growth factor
      receptor 2 (HER2) overexpression in patients with ductal carcinoma in situ
      (DCIS). PATIENTS AND METHODS: We identified patients with HER2-positive DCIS
      among a population of 1667 cases, prospectively diagnosed and surgically treated
      at the European Institute of Oncology from 1996 to 2008. Rates of subsequent DCIS
      or invasive cancer in HER2-positive disease were estimated. We evaluated
      Cumulative Incidence of In Situ Breast Cancer Recurrence (isBCR), INvasive Breast
      Cancer Recurrence (IBCR) and any Breast Cancer Recurrence (BCR). isBCR, IBCR and
      BCR were defined as the time from surgery to breast cancer recurrence as first
      event (in situ, invasive or both, respectively) or last visit in case of no
      events. RESULTS: We identified 560 (33.5%) patients with HER2-positive DCIS. The
      median follow-up was 7.6 years (interquartile range 5.9-9.5). We observed 422
      events out of 1667 patients, with 141 in situ recurrences, 201 invasive
      recurrences and 80 other events (64 second primaries and 16 deaths). The 10-year
      isBCR proportions were 11.8% [95% confidence interval (CI) 9.0% to 15.4%] in the
      HER2-positive group and 8.8% (95% CI 6.9% to 11.0%) in the HER2-negative group
      (Gray test, P = 0.010). At multivariable analysis, the adjusted risk of isBCR was
      higher in the HER2-positive group than in the HER2-negative group [hazard ratio
      (HR) HER2 positive versus negative: 1.59 (95% CI 1.06-2.39)]. We observed
      significant differences both in BCR and isBCR for patients treated by
      quadrantectomy without radiotherapy versus patients treated with radiotherapy
      [adjusted HR HER2 positive versus negative: 1.53 (95% CI 1.07-2.18) and adjusted
      HR HER2 positive versus negative: 2.18 (95% CI 2.18-3.69), respectively].
      CONCLUSION: HER2 overexpression predicts an increased risk of isBCR. Radiotherapy
      reduces local failure rates in HER2-positive DCIS.

PMID- 25600569
TI  - Electronic clinical safety reporting system: a benefits evaluation.
AB  - BACKGROUND: Eastern Health, a large health care organization in Newfoundland and
      Labrador (NL), started a staged implementation of an electronic occurrence
      reporting system (used interchangeably with "clinical safety reporting system")
      in 2008, completing Phase One in 2009. The electronic clinical safety reporting
      system (CSRS) was designed to replace a paper-based system. The CSRS involves
      reporting on occurrences such as falls, safety/security issues, medication
      errors, treatment and procedural mishaps, medical equipment malfunctions, and
      close calls. The electronic system was purchased from a vendor in the United
      Kingdom that had implemented the system in the United Kingdom and other places,
      such as British Columbia. The main objective of the new system was to improve the
      reporting process with the goal of improving clinical safety. The project was
      funded jointly by Eastern Health and Canada Health Infoway. OBJECTIVE: The
      objectives of the evaluation were to: (1) assess the CSRS on achieving its stated
      objectives (particularly, the benefits realized and lessons learned), and (2)
      identify contributions, if any, that can be made to the emerging field of
      electronic clinical safety reporting. METHODS: The evaluation involved mixed
      methods, including extensive stakeholder participation, pre/post comparative
      study design, and triangulation of data where possible. The data were collected
      from several sources, such as project documentation, occurrence reporting
      records, stakeholder workshops, surveys, focus groups, and key informant
      interviews. RESULTS: The findings provided evidence that frontline staff and
      managers support the CSRS, identifying both benefits and areas for improvement.
      Many benefits were realized, such as increases in the number of occurrences
      reported, in occurrences reported within 48 hours, in occurrences reported by
      staff other than registered nurses, in close calls reported, and improved
      timelines for notification. There was also user satisfaction with the tool
      regarding ease of use, accessibility, and consistency. The implementation process
      encountered challenges related to customizing the software and the development of
      the classification system for coding occurrences. This impacted on the ability of
      the managers to close-out files in a timely fashion. The issues that were
      identified, and suggestions for improvements to the form itself, were shared with
      the Project Team as soon as they were noted. Changes were made to the system
      before the rollout. CONCLUSIONS: There were many benefits realized from the new
      system that can contribute to improved clinical safety. The participants
      preferred the electronic system over the paper-based system. The lessons learned
      during the implementation process resulted in recommendations that informed the
      rollout of the system in Eastern Health, and in other health care organizations
      in the province of Newfoundland and Labrador. This study also informed the
      evaluation of other health organizations in the province, which was completed in
      2013.

PMID- 25600568
TI  - Continuation or reintroduction of bevacizumab beyond progression to first-line
      therapy in metastatic colorectal cancer: final results of the randomized BEBYP
      trial.
AB  - BACKGROUND: The combination of bevacizumab with fluorouracil-based chemotherapy
      is a standard first-line treatment option in metastatic colorectal cancer (mCRC).
      We studied the efficacy of continuing or reintroducing bevacizumab in combination
      with second-line chemotherapy after progression to bevacizumab-based first-line
      therapy. PATIENTS AND METHODS: In this phase III study, patients with mCRC
      treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were
      randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on first
      line regimen) with or without bevacizumab. The primary end point was progression
      free survival. To detect a hazard ratio (HR) for progression of 0.70 with an
      alpha and beta error of 0.05 and 0.20, respectively, 262 patients were required.
      RESULTS: In consideration of the results of the ML18147 trial, the study was
      prematurely stopped. Between April 2008 and May 2012, a total of 185 patients
      were randomized. Bevacizumab-free interval was longer than 3 months in 43% of
      patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm.
      At a median follow-up of 45.3 months, the median progression-free survival was
      5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group
      [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank
      P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups
      analyzed and in particular in patients who had continued or reintroduced
      bevacizumab. An improved overall survival was also observed in the bevacizumab
      arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043).
      Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups
      (17% and 21%; P = 0.573). Toxicity profile was consistent with previously
      reported data. CONCLUSIONS: This study demonstrates that the continuation or the
      reintroduction of bevacizumab with second-line chemotherapy beyond first
      progression improves the outcome and supports the use of this strategy in the
      treatment of mCRC. ClinicalTrials.gov number: NCT00720512.

PMID- 25600570
TI  - Hydrogen peroxide and hypochlorous acid influx through the major S. Typhimurium
      porin OmpD is affected by substitution of key residues of the channel.
AB  - OmpD is the major Salmonella enterica serovar Typhimurium (S. Typhimurium) porin
      and mediates hydrogen peroxide (H2O2) influx. The results described herein extend
      this finding to hypochlorous acid (HOCl), another reactive oxygen species that is
      also part of the oxidative burst generated by the phagosome. S. Typhimurium cells
      lacking OmpD show decreased HOCl influx, and OmpD-reconstituted proteoliposomes
      show an increase in the uptake of the toxic compound. To understand this
      physiologically relevant process, we investigated the role of key OmpD residues
      in H2O2 and NaOCl transport. Using a theoretical approach, residue K16 was
      defined as a major contributor to the channel electrostatic properties, and E111
      was shown to directly participate in the size-exclusion limit of the channel.
      Together, we provide theoretical, genetic, and biochemical evidence that OmpD
      mediates H2O2 and NaOCl uptake, and that key residues of the channel are
      implicated in this process. 

PMID- 25600571
TI  - Enhancing the heat stability and kinetic parameters of the maize endosperm ADP
      glucose pyrophosphorylase using iterative saturation mutagenesis.
AB  - Iterative saturation mutagenesis (ISM) has been used to improve the
      thermostability of maize endosperm ADP-glucose pyrophosphorylase (AGPase), a
      highly-regulated, rate-limiting and temperature-sensitive enzyme essential for
      starch biosynthesis. The thermo-sensitivity of heterotetrameric AGPase has been
      linked to grain loss in cereals and improving this property might therefore have
      direct impacts on grain yield. Nine amino acids were selected for site-saturation
      mutagenesis on the basis of elevated B-factors in the crystal structure of the
      closest available homolog (a small subunit homotetramer of potato AGPase). After
      each round of mutagenesis, iodine staining and antibody capture activity assays
      at varying temperatures were used to select the optimum positions and amino acid
      changes for the next rounds of mutagenesis. After three iterations, the signals
      from whole-colony iodine staining were saturated and a heat stable AGPase variant
      was obtained. Kinetic studies of the heat stable mutant showed that it also had
      an unexpected increased affinity for the activator, 3-PGA. This is particularly
      valuable as both the temperature stability and allosteric properties of AGPase
      significantly influence grain yield. 

PMID- 25600572
TI  - Efficacy and safety of a novel combination of two oral chelators
      deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded
      young beta thalassemia major patients.
AB  - OBJECTIVE: Minimal data are available on the combined two oral iron chelators in
      beta-thalassemia major (beta-TM). Comparison of safety, efficacy, compliance,
      treatment satisfaction, and quality of life (QoL) of two regimens: deferiprone
      (DFP) and deferoxamine (DFO) versus DFP and deferasirox (DFX) were studied.
      METHODS: A prospective randomized trial (NCT01511848) was conducted on 96 young
      beta-TM patients with severe iron overload. Patients were randomized to receive
      either DFP with DFO (arm 1) or DFP and DFX (arm 2). Efficacy endpoints were the
      difference between two groups in the change of serum ferritin (SF), liver iron
      concentration (LIC), cardiac MRI, and quality of life (QoL). RESULTS: In both
      arms, SF and LIC at 12 months were significantly lower, and geometric mean
      cardiac T2* was higher compared to baseline. On regression analysis of change in
      each studied variable against time, significant difference between slopes of the
      two groups regarding cardiac T2* (P = 0.001 with more improvement in DFP/DFX
      patients) was found with no significant difference in the slopes of SF and LIC (P
      = 0.218 and 0.340). CONCLUSION: Both iron chelation combination regimens were
      equally effective in reducing iron overload and improving QoL.DFP/DFX combination
      proved superior in improving cardiac T2*, treatment compliance, and patients
      satisfaction with no greater adverse events.

PMID- 25600573
TI  - Efficiency of professional tooth brushing before ultrasonic scaling.
AB  - OBJECTIVES: This study aimed to examine the effect of dental plaque biofilm
      removal with a toothbrush, an interdental brush and dental floss by a dental
      hygienist prior to ultrasonic scaling on treatment times and client satisfaction.
      METHODS: This study was conducted among adults who received scaling after
      agreeing to participate in this study at a dental clinic in Seoul, Korea, from
      July to September 2012. Thirty-seven subjects received modified scaling (M
      scaling) which is ultrasonic scaling after plaque control with a toothbrush and
      dental floss by a dental hygienist, and 37 subjects received routine ultrasonic
      scaling (R-scaling). Univariate and multivariate analyses and chi-squared and t
      tests were conducted using SAS. This study was approved by the Kangwon
      Institutional Review Board. RESULTS: Significant differences were found between
      the outcomes of M- and R-scaling for both the ultrasonic scaling time (M-scaling,
      7.41 +/- 6.18 min; R-scaling, 23.22 +/- 6.92 min) and the total tooth cleaning
      time (M-scaling, 15.92 +/- 7.70 min; R-scaling, 23.22 +/- 6.92 min) (P < 0.001).
      Subject satisfaction with the scaling process was not significantly different
      between M-scaling (4.54 +/- 0.80) and R-scaling (4.84 +/- 0.44). CONCLUSIONS:
      These findings indicated that removing the dental plaque biofilm with a
      toothbrush and dental floss by a hygienist before scaling with an ultrasonic
      device was more effective in reducing the working time of the dental hygienist.

PMID- 25600576
TI  - [Nursing care of a patient with bipolar disorder and lithium-induced nephrogenic
      diabetes insipidus].
AB  - Bipolar disorder is one of the most common, severe and persistent mental
      disorders. The evaluation of all data and variables related to bipolar disorder
      is a difficult task, because there is no clear agreement on what should be
      included in this category. One of the traditional treatments for this disease is
      the lithium metal that is administered in the form of lithium salt. Lithium has a
      narrow therapeutic window and there is a significant risk of complications
      arising from its use, mainly neurological and renal. In the case presented, the
      preparation of a care plan is described for a patient diagnosed with bipolar
      disorder who suffered a complication with lithium treatment. To do this, it was
      decided to use a standardized care plan and later completed it with diagnostic,
      objectives and interventions to the specific needs of the patient, aimed at
      achieving optimal levels of independence. 

PMID- 25600574
TI  - Procalcitonin-guided therapy may reduce length of antibiotic treatment in
      intensive care unit patients with secondary peritonitis: A multicenter
      retrospective study.
AB  - PURPOSE: Because procalcitonin (PCT) might be surrogate for antimicrobial
      discontinuation in general intensive care units (ICUs), this study explored its
      use for secondary peritonitis in 4 surgical ICUs (SICUs). METHODS: A
      retrospective study including all consecutive patients with secondary
      peritonitis, controlled infection source, requiring surgery, and at least 48-hour
      SICU admission was performed (June 2012-June 2013). Patients were divided
      following notations in medical records into PCT-guided (notation of PCT-based
      antibiotic discontinuation) and non-PCT-guided (no notation) groups. RESULTS: A
      total of 121 patients (52 PCT-guided, 69 non-PCT-guided) were included. No
      differences in clinical scores, biomarkers, or septic shock (30 [57.7%] PCT
      guided vs 40 [58.0%] non-PCT-guided) were found. Length of intra-SICU (median,
      5.0 days; both groups) or in-hospital (median, 20.0 vs 17.5 days) stay, and
      mortality intra-SICU (9.6% vs 13.0%), 28-day (15.4% vs 20.3%), or in-hospital
      (19.2% vs 29.0%) were not significantly different (PCT-guided vs non-PCT-guided).
      In septic shock patients, no mortality differences were found (PCT-guided vs non
      PCT-guided): 16.7% vs 22.5% (intra-SICU), 26.7% vs 32.5% (28-day), and 33.3% vs
      42.5% (in-hospital). Treatment was shorter in the PCT-guided group (5.1 +/-2.1 vs
      10.2 +/- 3.7 days, P < .001), without differences between patients with and
      without septic shock. CONCLUSION: Procalcitonin guidance produced 50% reduction
      in antibiotic duration (P < .001, log-rank test).

PMID- 25600577
TI  - Effect of brief cetylpyridinium chloride treatments during early and mature
      cariogenic biofilm formation.
AB  - OBJECTIVES: The aim of this study was to investigate the antibiofilm activity of
      brief cetylpyridinium chloride (CPC) treatments during early and mature
      Streptococcus mutans biofilm formation. METHODS: Streptococcus mutans biofilms
      were formed on saliva-coated hydroxyapatite disks. The biofilms were treated with
      CPC twice daily (1 min/treatment) from 0 to 50 h or from 48 to 98 h.
      Acidogenicity, dry weight, viability, and water-insoluble extracellular
      polysaccharides of the biofilms were analyzed. Confocal laser scanning microscopy
      (CLSM) images were obtained to confirm the antibiofilm activity during mature
      biofilm formation and to evaluate the relationship between treatment time and the
      antibiofilm activity. RESULTS: CPC showed complete antibiofilm activity during
      early biofilm formation at 0.025% to 0.1%. During mature biofilm formation, CPC
      inhibited dry weight, viability, and acidogenicity at 0.075% and 0.1%. CLSM
      images showed an increase in dead cells at 0.075% and 0.1% CPC. The antibiofilm
      activity during mature biofilm formation increased as the concentration of CPC
      increased. Images from the CLSM study also showed that antibiofilm activity
      increased as treatment time increased. CONCLUSION: Our findings suggest that
      brief CPC treatments have strong anti-S. mutans biofilm activity. The antibiofilm
      activity was dependent on the stage of biofilm formation, CPC concentration, and
      treatment time.

PMID- 25600578
TI  - Individualizing prophylaxis in hemophilia: a review.
AB  - Prophylaxis is considered optimal care for patients with severe hemophilia to
      prevent bleeding, including hemarthroses, which may cause arthropathy with
      chronic pain, occupational impairment and progressive loss of mobility. Questions
      remain regarding the optimal delivery of prophylaxis including how to
      individualize prophylaxis and optimize outcomes for each patient. Designing a
      prophylactic regimen for severe hemophilia must account for each patient's unique
      disease course, bleeding pattern, presence/absence of joint damage,
      pharmacokinetic profile, level of physical activity and adherence to treatment.
      Standard weight-based prophylaxis regimens and regimens optimized by bleeding
      phenotype (i.e., patients are 'allowed' to bleed to dose optimization) fail to
      prevent complications in many patients. Pharmacokinetic-guided dosing enables
      precise adjustment of dosing level and frequency to maintain adequate hemostatic
      levels and prevent bleeding. Optimal outcomes, such as reducing or eliminating
      hemorrhages, preventing or minimizing joint damage, and improving quality of
      life, can be achieved through an individualized care approach. 

PMID- 25600579
TI  - Controlled Release, Intestinal Transport, and Oral Bioavailablity of Paclitaxel
      Can be Considerably Increased Using Suitably Tailored Pegylated Poly(Anhydride)
      Nanoparticles.
AB  - The aim of the work was to evaluate in vitro and in vivo the effect of the
      addition of poly(ethylene glycol) (PEG) to paclitaxel (PTX)-cyclodextrin
      poly(anhydride) nanoparticles. For this, PTX in poly(anhydride) nanoparticles
      complexed with cyclodextrins (either 2-hydroxypropyl-beta-cyclodextrin or beta
      cyclodextrin) and combined with PEG 2000 were prepared by the solvent
      displacement method. Intestinal permeability in vitro and in vivo pharmacokinetic
      studies in C57BL/6J mice were performed. Nanoparticle formulations containing PTX
      increased its apparent permeability through rat intestine in vitro in the Ussing
      chambers, enhancing its permeability 10-15 times compared with commercial
      Taxol(r). In addition, in pharmacokinetic studies, drug plasma levels were
      observed for at least 24 h leading to a relative oral bioavailability between 60%
      and 80% for PTX complexed with cyclodextrin and loaded in pegylated
      poly(anhydride) nanoparticles after oral gavage. In all, PTX-cyclodextrin
      complexes encapsulated in pegylated nanoparticles managed to promote the
      intestinal uptake of the drug displaying sustained plasma levels after oral
      administration to laboratory animals with a more prolonged plasma profile
      compared with the formulation with no PEG at all. Therefore, pegylated
      poly(anhydride) nanoparticles represent a promising carrier for the oral delivery
      of PTX.

PMID- 25600580
TI  - Microbiota of regular sodium and sodium-reduced ready-to-eat meat products
      obtained from the retail market.
AB  - The aim of this study was to assess the influence of sodium content on the
      microbiota on the surface of ready-to-eat (RTE) meat products purchased from the
      retail market in Canada. Products, including sliced and sausage-type deli meats,
      were analysed with culture-dependent and culture-independent methods. Bacteria
      were identified from 23 brands of products from different meat processors with
      claims of sodium content ranging from 390 to 1200 mg per 100 g of product. Out of
      150 bacterial isolates, the most common were identified as Leuconostoc gelidum,
      Carnobacterium maltaromaticum, Brochothrix thermosphacta, and Leuconostoc
      gasicomitatum. Vacuum-packaged RTE deli sliced meat products had the largest
      population of bacteria. Leuconostocci were the most common isolates in this group
      of products, while carnobacteria were prevalent on products with moderate loads
      of bacteria. A higher incidence of carnobacteria and lower incidence of B.
      thermosphacta were detected on sodium-reduced products. Simpson's and Shannon
      Wiener indices showed that low sodium products (25%-50% less sodium) had an
      overall higher bacterial diversity. This was also observed when individual low
      sodium products were compared with their regular sodium counterpart. 

PMID- 25600581
TI  - The pH-dependent long-term stability of an amorphous manganese oxide in smelter
      polluted soils: implication for chemical stabilization of metals and metalloids.
AB  - An amorphous manganese oxide (AMO) and a Pb smelter-polluted agricultural soil
      amended with the AMO and incubated for 2 and 6 months were subjected to a pH
      static leaching procedure (pH 3-8) to verify the chemical stabilization effect on
      metals and metalloids. The AMO stability in pure water was pH-dependent with the
      highest Mn release at pH 3 (47% dissolved) and the lowest at pH 8 (0.14%
      dissolved). Secondary rhodochrosite (MnCO3) was formed at the AMO surfaces at
      pH>5. The AMO dissolved significantly less after 6 months of incubation.
      Sequential extraction analysis indicated that "labile" fraction of As, Pb and Sb
      in soil significantly decreased after AMO amendment. The pH-static experiments
      indicated that no effect on leaching was observed for Cd and Zn after AMO
      treatments, whereas the leaching of As, Cu, Pb and Sb decreased down to 20%, 35%,
      7% and 11% of the control, respectively. The remediation efficiency was more
      pronounced under acidic conditions and the time of incubation generally led to
      increased retention of the targeted contaminants. The AMO was found to be a
      promising agent for the chemical stabilization of polluted soils. 

PMID- 25600582
TI  - Highly active Pd-In/mesoporous alumina catalyst for nitrate reduction.
AB  - The catalytic reduction of nitrate is a promising technology for groundwater
      purification because it transforms nitrate into nitrogen and water. Recent
      studies have mainly focused on new catalysts with higher activities for the
      reduction of nitrate. Consequently, metal nanoparticles supported on mesoporous
      metal oxides have become a major research direction. However, the complex surface
      chemistry and porous structures of mesoporous metal oxides lead to a non-uniform
      distribution of metal nanoparticles, thereby resulting in a low catalytic
      efficiency. In this paper, a method for synthesizing the sustainable nitrate
      reduction catalyst Pd-In/Al2O3 with a dimensional structure is introduced. The
      TEM results indicated that Pd and In nanoparticles could efficiently disperse
      into the mesopores of the alumina. At room temperature in CO2-buffered water and
      under continuous H2 as the electron donor, the synthesized material (4.9 wt% Pd)
      was the most active at a Pd-In ratio of 4, with a first-order rate constant
      (k(obs) = 0.241 L min(-1) g(cata)(-1)) that was 1.3* higher than that of
      conventional Pd-In/Al2O3 (5 wt% Pd; 0.19 L min(-1) g(cata)(-1)). The Pd
      In/mesoporous alumina is a promising catalyst for improving the catalytic
      reduction of nitrate.

PMID- 25600583
TI  - Pre-operative fibrinogen supplementation in cardiac surgery patients: an
      evaluation of different trigger values.
AB  - BACKGROUND: Pre-operative fibrinogen levels are negatively associated with
      postoperative bleeding in cardiac surgery patients. The guidelines of the
      European Society of Anaesthesiology consider the possibility of a prophylactic
      pre-operative supplementation in patients with fibrinogen levels<'3.8 g/l. The
      present study is a reanalysis of published data aimed to define the diagnostic
      accuracy of different values of pre-operative fibrinogen levels in predicting
      severe post-operative bleeding. METHODS: Data were retrieved for 2154 patients in
      four different studies. Severe bleeding (SB) was defined as a post-operative
      chest drain output>1 l/12 h. Diagnostic accuracy for prediction of SB was tested
      at three cutoff values of pre-operative fibrinogen (2.5 g/l, 3.0 g/l, and 3.8
      g/l). RESULTS: At all the three cutoff values, pre-operative fibrinogen levels
      had an excellent negative predictive value, ranging from 86% to 100%. Conversely,
      the positive predictive value was poor at all the cutoff levels: 12% (3.8 g/l),
      14% (3.0 g/l), and 19% (2.5 g/l). Overall, the accuracy of pre-operative
      fibrinogen levels for the prediction of SB was poor. A strategy based on pre
      operative fibrinogen supplementation would lead to inappropriate treatment in >
      80% of the treated patients. Overall, a trigger value of 3.8 g/l would result in
      an inappropriate treatment in 52% of the patients, of 3.0 g/l in 20% of the
      patients, and of 2.5 g/l in 4% of the patients. CONCLUSION: Correction of pre
      operative fibrinogen levels below 3.8 g/l would lead to an excessive rate of
      inappropriate interventions. Values below 2.5 g/l could be considered.

PMID- 25600584
TI  - Dermoscopy is useful for bed bug (Cimex lectularius) bites.

PMID- 25600585
TI  - Neurobiological roots of language in primate audition: common computational
      properties.
AB  - Here, we present a new perspective on an old question: how does the neurobiology
      of human language relate to brain systems in nonhuman primates? We argue that
      higher-order language combinatorics, including sentence and discourse processing,
      can be situated in a unified, cross-species dorsal-ventral streams architecture
      for higher auditory processing, and that the functions of the dorsal and ventral
      streams in higher-order language processing can be grounded in their respective
      computational properties in primate audition. This view challenges an assumption,
      common in the cognitive sciences, that a nonhuman primate model forms an
      inherently inadequate basis for modeling higher-level language functions.

PMID- 25600587
TI  - 5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the
      human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-kappaB
      dependent mechanism.
AB  - Recent studies have established the role of mid-chain hydroxyeicosatetraenoic
      acids (HETEs) in the development of cardiovascular disease. Mid-chain HETEs have
      been reported to have vasoconstrictive and pro-inflammatory effects. However,
      whether mid-chain HETEs can induce cardiac hypertrophy remains unclear.
      Therefore, the overall objective of the present study was to elucidate the
      potential hypertrophic effect of mid-chain HETEs in the human ventricular
      cardiomyocytes, RL-14 cells, and to explore the mechanisms involved. For this
      purpose, RL-14 cells were treated with increasing concentrations of mid-chain
      HETEs (2.5, 5, 10 and 20 uM). Thereafter, the cardiac hypertrophy markers and
      cell size were determined using real-time polymerase chain reaction and phase
      contrast imaging, respectively. Phosphorylated mitogen-activated protein kinase
      (MAPK) level and nuclear factor kappa B (NF-kappaB) binding activity were
      determined. Our results showed that mid-chain HETEs induced cellular hypertrophy
      in RL-14 cells as evidenced by the induction of cardiac hypertrophy markers,
      alpha- and beta-myocin heavy chain and atrial and brain natriuretic peptide as
      well as the increase in cell size. Mechanistically, all mid-chain HETEs were able
      to induce the binding activity of NF-kappaB to its responsive element in a HETE
      dependent manner, and they significantly induced the phosphorylation of ERK 1/2.
      The induction of cellular hypertrophy was associated with proportional increase
      in the formation of dihydroxyeicosatrienoic acids parallel to the increase of
      soluble epoxide hydrolase enzyme activity. In conclusion, our study provides the
      first evidence that mid-chain HETEs induce cellular hypertrophy in RL-14 cells
      through MAPK- and NF-kappaB-dependent mechanism. 

PMID- 25600586
TI  - How the hippocampus preserves order: the role of prediction and context.
AB  - Remembering the sequence of events is critical for deriving meaning from our
      experiences and guiding behavior. Prior investigations into the function of the
      human hippocampus have focused on its more general role in associative binding,
      but recent work has focused on understanding its specific role in encoding and
      preserving the temporal order of experiences. In this review we summarize recent
      work in humans examining hippocampal contributions to sequence learning. We
      distinguish the learning of sequential relationships through repetition from the
      rapid, episodic acquisition of sequential associations. Taken together, this
      research begins to clarify the link between hippocampal representations and the
      preservation of the order of events. 

PMID- 25600588
TI  - Cancer risk assessment foundation unraveling: new historical evidence reveals
      that the US National Academy of Sciences (US NAS), Biological Effects of Atomic
      Radiation (BEAR) Committee Genetics Panel falsified the research record to
      promote acceptance of the LNT.
AB  - The NAS Genetics Panel (1956) recommended a switch from a threshold to a linear
      dose response for radiation risk assessment. To support this recommendation,
      geneticists on the panel provided individual estimates of the number of children
      in subsequent generations (one to ten) that would be adversely affected due to
      transgenerational reproductive cell mutations. It was hoped that there would be
      close agreement among the individual risk estimates. However, extremely large
      ranges of variability and uncertainty characterized the wildly divergent expert
      estimates. The panel members believed that sharing these estimates with the
      scientific community and general public would strongly undercut their linearity
      recommendation, as it would have only highlighted their own substantial
      uncertainties. Essentially, their technical report in the journal Science omitted
      and misrepresented key adverse reproductive findings in an effort to ensure
      support for their linearity recommendation. These omissions and
      misrepresentations not only belie the notion of an impartial and independent
      appraisal by the NAS Panel, but also amount to falsification and fabrication of
      the research record at the highest possible level, leading ultimately to the
      adoption of LNT by governments worldwide. Based on previously unexamined
      correspondence among panel members and Genetics Panel meeting transcripts, this
      paper provides the first documentation of these historical developments. 

PMID- 25600589
TI  - Intrathyroidal multiloculated proliferating thymic cyst.
AB  - Ectopic thymic tissue in neck is not uncommon; however, ectopic thymic cysts in
      neck are rare and intrathyroidal thymic cyst is still rarer. Multilocular
      proliferating thymic cyst is a rare entity and very few cases are described in
      mediastinum. We present the first case of a 73-year-old male with an
      intrathyroidal multilocular proliferating thymic cyst mimicking thyroid
      malignancy radiologically. 

PMID- 25600590
TI  - Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and
      viral oncogene-mediated p53 inactivation.
AB  - CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most
      frequently mutated tumour-suppressor gene that functions in a context-dependent
      manner. Here we show that both targeted mutation and short hairpin RNA (shRNA)
      silencing of CD24 retard the growth, progression and metastasis of prostate
      cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased
      ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24
      silencing prevents functional inactivation of p53 by both somatic mutation and
      viral oncogenes, including the SV40 large T antigen and human papilloma virus 16
      E6-antigen. In support of the functional interaction between CD24 and p53, in
      silico analyses reveal that TP53 mutates at a higher rate among glioma and
      prostate cancer samples with higher CD24 mRNA levels. These data provide a
      general mechanism for functional inactivation of ARF and reveal an important
      cellular context for genetic and viral inactivation of TP53. 

PMID- 25600591
TI  - Transient receptor potential vanilloid 4 inhibits rat HSC-T6 apoptosis through
      induction of autophagy.
AB  - Hepatic stellate cell (HSC) activation is a significant event in the development
      of liver fibrosis. Promoting the activated HSCs apoptosis contributes to the
      reversal of liver fibrosis. Autophagy is considered to be critical for many
      cellular and pathological processes including liver fibrosis. Transient receptor
      potential vanilloid 4 (TRPV4), another member of the transient receptor potential
      (TRP) channel, is proved to be a vital modulator in regulating HSC proliferation
      during liver fibrosis. However, the precise mechanism of TRPV4 on HSC apoptosis
      is still unclear. Here, we explored the role of TRPV4 in regulating HSC-T6 cell
      apoptosis. Our study detected that the expressions of TRPV4 mRNA and protein were
      dramatically increased in HSC-T6 in response to TGF-beta1 stimulation by qRT-PCR
      and Western blot. Moreover, the HSC-T6 transfected with si-TRPV4 increased
      apoptosis and inhibited autophagy. In addition, the HSC-T6 treated with 4alpha
      phorbol 12,13-didecanoate results in suppression of apoptosis and increase of
      autophagy. Furthermore, we indicated that TRPV4 induces autophagy by regulating
      AKT signaling pathway. In addition, we found that blockade of autophagy by
      chemical antagonists chloroquine (CQ) leads to increased apoptosis. Furthermore,
      blocking autophagy by CQ did not lead to a distinct change with or without TRPV4
      over-expression. These results indicated that TRPV4 could inhibit HSCs apoptosis
      partially by regulating autophagy-dependent AKT signaling pathway activation. 

PMID- 25600592
TI  - Bone marrow stromal cells transplantation combined with ultrashortwave therapy
      promotes functional recovery on spinal cord injury in rats.
AB  - OBJECTIVE: This study investigated the effects of bone marrow stromal cells
      (BMSCs) transplantation combined with low dose ultrashortwave (USW) radiation on
      functional recovery from spinal cord injury (SCI) in rats. Female Sprague-Dawley
      rats (n = 64) were randomly divided into five groups: sham-operated, as well as
      control, USW, BMSCs, and BMSCs + USW that were subjected to spinal cord
      contusion. BMSCs were transplanted into rats in the BMSCs and BMSCs+USW groups,
      while those in the USW and BMSCs + USW were exposed to radiation; Basso-Beattie
      Bresnahan (BBB) tests were performed before the operation and at 1-week intervals
      after SCI for 7 weeks. 7 weeks later, animals were assessed footprint pattern,
      motor evoked potential (MEP), histological features, and expression of the ED1
      and glial fibrillary acidic protein (GFAP), markers of activated macrophages and
      astrocytes, respectively, in the lesion area. BBB scores were higher in the BMSCs
      + USW than in the BMSCs and control groups. The USW and BMSCs + USW groups had
      improved coordination compared to the BMSCs and control groups (P < 0.01 and P <
      0.001, respectively, vs. control). BMSCs + USW rats had a lower ratio of
      lesion/cavity to spinal cord area than the other injured rats, and also had
      expression of GFAP in transplanted BMSCs. All treatment groups had lower ED1
      expression and MEP latency than the controls (P < 0.01 and P < 0.001,
      respectively). The results indicate that BMSCs transplantation combined with USW
      radiation is more effective than either treatment alone in promoting functional
      recovery after SCI, possibly due to concomitant suppression of inflammation and
      spinal cord repair.

PMID- 25600595
TI  - Aggravation of left ventricular dysfunction in patients with biopsy-proven
      cardiac human herpesvirus A and B infection.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6) A and B are lymphotropic viruses with
      life-long persistence, primarily associated with non-cardiac diseases, and
      discussed as a possible etiologic factor of myocarditis and cardiomyopathy.
      OBJECTIVE: To analyze the long-term spontaneous course of cardiac patients
      suffering from suspected inflammatory cardiomyopathy (CMi) with persisting HHV-6
      A and B infections by follow-up biopsies. STUDY DESIGN: We prospectively
      evaluated patients (n=73) with biopsy-proven viral HHV-6 A and B infection in
      endomyocardial biopsies (EMBs), followed up by reanalysis of EMBs and left
      ventricular ejection fraction (LV-EF) measurements after a median period of 8.8
      months (range 4-73 months). Beyond, we studied HHV-6 prevalence in isolated
      peripheral blood cells (PBCs) and HHV-6 species in EMBs. HHV-6 species-specific
      cellular infection sites within the myocardium were identified by
      immunohistochemistry (IHC). RESULTS: We identified 73 patients with cardiac HHV-6
      A and B persistence or newly detected in follow-up EMB (95.0% B). Proof of HHV-6
      in PBCs was primarily associated with A. Persistence of cardiac HHV-6 B genome
      was significantly associated with cardiac dysfunction at follow-up (LV-EF
      deteriorated from 58.2+/-16.0 to 51.8+/-17.2%, p<0.001), and LV improvement was
      observed when HHV-6 B persistence resolved (LV-EF increased from 54.9+/-15.4 to
      60.7+/-13.1%, p<0.001). CONCLUSIONS: Persistence of cardiac HHV-6 B genomes was
      significantly associated with cardiac dysfunction, and hemodynamic parameters
      improved in association with HHV-6 B clearance.

PMID- 25600594
TI  - The GI-CDF module of Arabidopsis affects freezing tolerance and growth as well as
      flowering.
AB  - Plants monitor and integrate temperature, photoperiod and light quality signals
      to respond to continuous changes in their environment. The GIGANTEA (GI) protein
      is central in diverse signaling pathways, including photoperiodic, sugar and
      light signaling pathways, stress responses and circadian clock regulation.
      Previously, GI was shown to activate expression of the key floral regulators
      CONSTANS (CO) and FLOWERING LOCUS T (FT) by facilitating degradation of a family
      of CYCLING DOF FACTOR (CDF) transcriptional repressors. However, whether CDFs are
      implicated in other processes affected by GI remains unclear. We investigated the
      contribution of the GI-CDF module to traits that depend on GI. Transcriptome
      profiling indicated that mutations in GI and the CDF genes have antagonistic
      effects on expression of a wider set of genes than CO and FT, whilst other genes
      are regulated by GI independently of the CDFs. Detailed expression studies
      followed by phenotypic assays showed that the CDFs function downstream of GI,
      influencing responses to freezing temperatures and growth, but are not necessary
      for proper clock function. Thus GI-mediated regulation of CDFs contributes to
      several processes in addition to flowering, but is not implicated in all of the
      traits influenced by GI. 

PMID- 25600596
TI  - Up-regulation of the monocyte chemotactic protein-3 in sera from bone marrow
      transplanted children with torquetenovirus infection.
AB  - BACKGROUND: Torquetenovirus (TTV) represents a commensal human virus producing
      life-long viremia in approximately 80% of healthy individuals of all ages. A
      potential pathogenic role for TTV has been suggested in immunocompromised
      patients with hepatitis of unknown etiology sustained by strong proinflammatory
      cytokines. OBJECTIVES: The aim of this study was to investigate the sera
      immunological profile linked to TTV infection in bone marrow transplant (BMT)
      children with liver injury. STUDY DESIGN: TTV infection was assessed in sera from
      27 BMT patients with altered hepatic parameters and histological features, by the
      use of quantitative real-time PCR, along with TTV genogroups and coinfection with
      HEV. The qualitative and quantitative nature of soluble inflammatory factors was
      evaluated studying a large set of cytokines using the Bioplex platform. As
      controls, sera from 22 healthy children negative for serological and molecular
      hepatitis markers including TTV and HEV, and for autoimmune diseases, were
      selected. RESULTS AND CONCLUSIONS: TTV was detected in 81.4% of BMT patients with
      a viral load ranging from 10(5) to 10(9) copies/mL. All samples were HEV-RNA
      negative. A pattern of cytokines, IFN-gamma, TNF-alpha, FGF-basic (p<0.01) and
      MCP-3 (p<0.001) was found significantly highly expressed in TTV-positive patients
      compared to TTV-negative and controls. Of note, MCP-3 chemokine showed the
      highest sera concentration independently of the amount of TTV load and the status
      of immune system deregulation (p<0.001). In this pilot study for the first time,
      a positive association was found between TTV and increased level of MCP-3
      suggesting a indirect role of TTV in liver injury.

PMID- 25600598
TI  - A study of family clustering in two young girls with novel avian influenza A
      (H7N9) in Dongyang, Zhejiang Province, in 2014.
AB  - BACKGROUND: The avian influenza A H7N9 virus, previously unknown in humans, has
      infected humans in many areas of China since February 2013. Here we report on a
      clustering case of H7N9 in two little girls in one family in Dongyang city,
      Jinhua area, Zhejiang Province. OBJECTIVES: To determine (1) whether the
      infections were due to person-to-person transmission or to co-exposure to poultry
      and (2) the prevalence of this novel H7N9 virus in Dongyang inferred by this
      family clustering case. STUDY DESIGN: Samples were collected from patients and
      environment. We undertook detailed epidemiological investigations and laboratory
      work. Phylogenetic analyses were done based on the sequenced genomes. The
      concentration of cytokines and chemokines in the serum was detected by cytometric
      bead array analyses. RESULTS: A mixture of H7 and H9 was detected from the
      environmental sample. The three H7N9 viruses shared one infection source. The
      index patient who had significantly higher levels of IL-4, IL-8 and IL-10
      suffered severe infection. CONCLUSIONS: Based on a comparison with previous
      isolations of the virus in 2013, H7N9 has evolved different lineages through
      recombination with local H9N2 viruses. Determining whether it was human-to-human
      transmission or exposure to the same live poultry, since both patients had
      identical exposure histories, was ambiguous. The results from the cytokine
      analyses agreed with the conclusion that H7N9 severity is associated with a
      higher level of cytokines/chemokines. Long term influenza surveillance remains
      essential to allow for early warning of potential transmission events.

PMID- 25600599
TI  - Monitoring and improving the sensitivity of dengue nested RT-PCR used in
      longitudinal surveillance in Thailand.
AB  - BACKGROUND: AFRIMS longitudinal dengue surveillance in Thailand depends on the
      nested RT-PCR and the dengue IgM/IgG ELISA. OBJECTIVE: To examine and improve the
      sensitivity of the nested RT-PCR using a panel of archived samples collected
      during dengue surveillance. STUDY DESIGN: A retrospective analysis of 16,454
      dengue IgM/IgG ELISA positive cases collected between 2000 and 2013 was done to
      investigate the sensitivity of the nested RT-PCR. From these cases, 318 acute
      serum specimens or extracted RNA, previously found to be negative by the nested
      RT-PCR, were tested using TaqMan real-time RT-PCR (TaqMan rRT-PCR). To improve
      the sensitivity of nested RT-PCR, we designed a new primer based on nucleotide
      sequences from contemporary strains found to be positive by the TaqMan rRT-PCR.
      Sensitivity of the new nested PCR was calculated using a panel of 87 samples
      collected during 2011-2013. RESULTS AND CONCLUSION: The percentage of dengue
      IgM/IgG ELISA positive cases that were negative by the nested RT-PCR varied from
      17% to 42% for all serotypes depending on the year. Using TaqMan rRT-PCR, dengue
      RNA was detected in 194 (61%) of the 318 acute sera or extracted RNA previously
      found to be negative by the nested RT-PCR. The newly designed DENV-1 specific
      primer increased the sensitivity of DENV-1 detection by the nested RT-PCR from
      48% to 88%, and of all 4 serotypes from 73% to 87%. These findings demonstrate
      the impact of genetic diversity and signal erosion on the sensitivity of PCR
      based methods.

PMID- 25600597
TI  - Hepatitis B virus infection in post-vaccination South Africa: occult HBV
      infection and circulating surface gene variants.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the prevalence
      of occult hepatitis B virus (HBV) infection and the HBV surface (S) gene variants
      circulating in the South African population after nearly two decades of universal
      hepatitis B vaccination. STUDY DESIGN: From a previous serosurvey, 201 serum
      samples with serological evidence of exposure to HBV were identified and these
      were stratified into post- and pre-vaccine introduction populations. For all
      samples, HBV DNA was screened and quantified using a real-time PCR assay and
      results analysed together with HBV serological markers. Where HIV results were
      available, subset analysis was performed. The HBV S gene was PCR-amplified and
      sequences analysed for a total of 37 isolates. RESULTS: The prevalence of occult
      HBV infection reduced from 70.4% in the pre-vaccine introduction era to 66.0%
      post-vaccine introduction. There was an association between HIV infection and an
      increase in prevalence of occult HBV infection within the post-vaccine
      introduction population, although this was not statistically significant.
      Furthermore, sequence analysis revealed the following HBV subgenotypes; A1
      (n=34), A2 (n=2) and a rare D4 isolate. HBV S gene variants, including diagnostic
      escape mutants were isolated. CONCLUSION: There was a decline in the prevalence
      of occult HBV infection in post-vaccination South Africa, although the disease
      burden remains significant in the HIV co-infected population. After nearly two
      decades of a universal hepatitis B vaccination programme, no positive selection
      of vaccine escape mutants were observed.

PMID- 25600600
TI  - Zika virus infections imported to Italy: clinical, immunological and virological
      findings, and public health implications.
AB  - We report the first two cases of laboratory confirmed Zika virus (ZIKV)
      infections imported into Italy from French Polynesia. Both patients presented
      with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema,
      and axillary and inguinal lymphadenopathy. One patient showed leukopenia with
      relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV
      seroconversion in both cases and on ZIKV RNA detection in one patient from acute
      serum sample. Sera from both patients exhibited cross-reactivity with dengue
      virus antigens. Our immunological analysis demonstrated that recovery from ZIKV
      infection is associated with restoration of normal numbers of immune cells in the
      periphery as well as with normal function of antigen-presenting cells. ZIKV is an
      emerging arbovirus, which has recently spread extensively in tourist destinations
      on several West Pacific islands. Returning viremic travelers may ignite
      autochthonous infections in countries like Italy, which are infested by Aedes
      albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and
      includes early diagnosis and timely notification of public health authorities in
      order to quickly implement adequate focal vector control measurements. 

PMID- 25600601
TI  - Hepatitis E in Scotland: assessment of HEV infection in two high-risk patient
      groups with elevated liver enzymes.

PMID- 25600602
TI  - Epidemiological history and genomic characterization of non-D1 HBV strains
      identified in Iran.
AB  - BACKGROUND: Hepatitis B virus (HBV) has been classified into eight genotypes and
      forty subgenotypes. Genotype D of HBV is the most worldwide distributed genotype
      and HBV subgenotype D1 has been isolated from Iranian patients. OBJECTIVE: To
      characterize for the first time complete genomes of recently emerged non-D1
      strains in Iran. STUDY DESIGN: HBV complete genomes isolated from 9 Iranian HBV
      carriers were sequenced. Different diversities of the ORFs were mapped and
      evolutionary history relationships were investigated. RESULTS: Phylogenetic
      analysis identified four D2 subgenotypes and five D3 subgenotypes of HBV in the
      studied patients. Of note, D2 strains clustered with strains from Lebanon and
      Syria. The time of the most recent common ancestor (TMRCA) of the first cluster
      of D2 was dated at 1953 (BCI=1926, 1976) while the second cluster was dated at
      1947 (BCI=1911, 1978). All five Iranian D3 strains formed a monophyletic cluster
      with Indian strain and dated back to 1967 (BCI=1946, 1987). Surprisingly, two D3
      strains had an adw2 subtype. Interestingly, more than 80% of the present strains
      showed precore mutations, while two isolates carried basal core promoter
      variation. CONCLUSION: Iranian D2 and D3 isolates were introduced on at least two
      and one occasion in Iran and diverged from west and south Asian HBV strains,
      respectively. Considering the impact of the different (sub) genotypes on clinical
      outcome, exploring the distinct mutational patterns of Iranian D1 and non-D1
      strains is of clinical importance.

PMID- 25600603
TI  - Cytokine modulation correlates with severity of monkeypox disease in humans.
AB  - BACKGROUND: Human monkeypox is a zoonotic disease endemic to parts of Africa.
      Similar to other orthopoxviruses, virus and host have considerable interactions
      through immunomodulation. These interactions likely drive the establishment of a
      productive infection and disease progression, resulting in the range of disease
      presentations and case fatality rates observed for members of the Orthopoxvirus
      genus. OBJECTIVES: Much of our understanding about the immune response to
      orthopoxvirus infection comes from either in vitro or in vivo studies performed
      in small animals or non-human primates. Here, we conducted a detailed assessment
      of cytokine responses to monkeypox virus using serum from acutely ill humans
      collected during monkeypox active disease surveillance (2005-2007) in the
      Democratic Republic of the Congo. STUDY DESIGN: Nineteen serum samples that were
      from patients with confirmed monkeypox virus infections were selected for
      cytokine profiling. Cytokine profiling was performed on the Bio-Rad Bioplex 100
      system using a 30-plex human cytokine panel. RESULTS: Cytokine profiling revealed
      elevated cytokine concentrations in all samples. Overproduction of certain
      cytokines (interleukin [IL]-2R, IL-10, and granulocyte macrophage-colony
      stimulating factor were observed in patients with serious disease (defined as
      >250 lesions based on the World Health Organization scoring system). CONCLUSIONS:
      The data suggest that cytokine modulation affects monkeypox disease severity in
      humans.

PMID- 25600604
TI  - A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive
      periodontitis - a case of virally induced periodontitis?
AB  - We present a 17-year old girl with DOCK-8 deficiency, severe untreated oral HSV-1
      infection and associated aggressive periodontitis. DOCK-8 deficiency is a primary
      immunodeficiency, caused by biallelicloss-of-function mutations in the DOCK8
      gene, often leading to severe viral and fungal mucocutaneous infections.
      Nevertheless, to date DOCK8 has not been associated with severe periodontitis and
      inflammatory bone loss around teeth. Understanding whether DOCK8 deficiency or
      severe HSV-1 infection underlies susceptibility to periodontitis is central to
      this case and may provide insights into susceptibility factors for periodontitis
      in the general population. Our clinical and microbiological data suggest that
      severe HSV-1 infection is the driver of periodontal inflammation in this case. 

PMID- 25600605
TI  - Acute HIV infection: improved algorithms for HIV testing.

PMID- 25600606
TI  - Cytomegalovirus infection in the Netherlands: seroprevalence, risk factors, and
      implications.
AB  - BACKGROUND: Cytomegalovirus (CMV) infections occur worldwide and are usually
      asymptomatic in healthy individuals. In fetuses and immunocompromised persons,
      they can cause severe disease and disabilities. OBJECTIVE: To determine the CMV
      seroprevalence and risk factors for CMV infection in the Netherlands. STUDY
      DESIGN: In a cross-sectional population-based study (PIENTER-2, 2006-2007), sera
      and questionnaire data were collected from 6386 individuals. Sera were tested for
      CMV-specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The CMV seroprevalence in the general population (6 months-79 years) was
      45.6%. Age and country of origin were the most prominent independent risk
      factors. The seroprevalence was significantly lower in native Dutch and Western
      individuals (41.5%) than in non-Western individuals (76.7%). Multivariable
      logistic regression analysis showed that age, lower educational level, first
      generation migrancy, and among native Dutch/Western individuals, female gender
      and having contact with young children, were independently associated with CMV
      seropositivity. The geometric mean concentrations of antibodies increased with
      age and were higher in women than in men. CONCLUSION: CMV seroprevalence in the
      Netherlands is relatively low compared to other countries. This is in line with
      our finding of a higher seroprevalence among migrants compared to the native
      population. The higher seroprevalence in women and individuals who have contact
      with young children is especially important for women of reproductive age.
      Preventing CMV infection in these women, through counseling on hygiene or
      possible future vaccination, may lead to a decrease of congenital CMV infections.

PMID- 25600607
TI  - The use of coroner's autopsy reports to validate the use of targeted swabbing
      rather than tissue collection for rapid confirmation of virological causes of
      sudden death in the community.
AB  - BACKGROUND AND OBJECTIVES: In this study, coroner's autopsy reports were used to
      validate results obtained from respiratory virus screening of swabs rather than
      tissue collected during autopsy in cases of adult death of unknown cause. STUDY
      DESIGN: Coroner's autopsy samples collected for respiratory virus screening
      between October 2010 and February 2011, were identified. Autopsy reports were
      requested from cases positive for a virus. Each report was reviewed to correlate
      findings at autopsy with the virology result and to determine whether the virus
      found was listed as a contributing factor in the death. RESULTS: Sixty-four
      coroner's autopsy cases were identified and a respiratory virus was found in 25
      cases. Influenza A(H1N1)pdm09 virus was found most frequently, then RSV and
      influenza B with a dual influenza A and B infection and a parainfluenza type 1.
      Where multiple sites were swabbed, the virus was detected in all sites. Autopsy
      reports for 12 cases were obtained each reporting findings consistent with
      respiratory infection. Influenza A was always listed as a contributing factor in
      the death whereas RSV was listed once and influenza B was omitted in one case.
      The quality of the reports was variable and full histology was less likely to be
      performed in the elderly. CONCLUSIONS: While coroner's reports supported the use
      of swabbing rather than tissue collection, the lack of consistency and omission
      of the virology findings as contributing factors to death means that the burden
      of viruses on mortality statistics will remain under-estimated particularly in
      the elderly.

PMID- 25600608
TI  - Severe acute pharyngotonsillitis due to herpes simplex virus type 2 in a young
      woman.
AB  - Whereas herpes simplex virus type 1 (HSV-1) is a recognized cause of acute
      oropharyngeal infection in young adults, HSV-2 infections are mostly associated
      with genital symptoms. We report a case of acute and prolonged febrile ulcerative
      pharyngotonsillitis with inflammatory syndrome which persisted despite antibiotic
      therapy for 8 days and required hospitalization in an 18-year old immune
      competent and sexually active female patient. HSV-2 was evidenced in tonsillar
      samples and blood by real time PCR, and HSV type-specific serology showed HSV-2
      primary infection. Despite delayed diagnosis, acyclovir treatment led to rapid
      clinical improvement. This case highlights HSV-2 as an unusual cause of
      pharyngotonsillitis that should be reminded in sexually active patients. 

PMID- 25600609
TI  - HIV-1 infection using dried blood spots can be confirmed by Bio-Rad GeeniusTM HIV
      1/2 confirmatory assay.
AB  - BACKGROUND: Confirmatory assays for HIV diagnosis are not well implemented in low
      income countries with limited infrastructures. GeeniusTM HIV 1/2 Confirmatory
      Assay is a single-use immunochromatographic test for the confirmation and
      differentiation of individual HIV-1/2 antibodies validated in venous whole blood,
      serum and plasma. However, dried blood specimens (DBS) are easier to collect,
      store and transport than plasma/serum in remote settings from limited resource
      countries and mobile populations. OBJECTIVES: To evaluate the confirmatory assay
      GeeniusTM HIV 1/2 for HIV diagnosis using DBS specimens. STUDY DESIGN: We
      collected DBS from 70 Guinean women previously diagnosed as HIV-1 infected by
      rapid tests using whole blood samples in Equatorial Guinea and from 25 HIV
      negative Guinean women and HIV-exposed infants diagnosed by molecular testing in
      Madrid. Geenius HIV 1/2 was performed by eluting two drops of dried blood from
      each patient and following the manufacturer instructions for the assay but using
      40MUl of the eluted blood as specimen. The results obtained were confirmed by
      western blot. RESULTS: GeeniusTM HIV 1/2 successfully confirmed the HIV-1
      positive and negative infection in all tested DBS specimens, providing 100%
      specificity [95% Confidence Interval (CI): 86.2%-100%]. No HIV 1/2 coinfections
      were found in the study cohort. This is the first report that proves a good
      performance of GeeniusTM HIV 1/2 for the HIV-1 infection confirmation using only
      two drops of dried blood. CONCLUSIONS: Our results approve the utility of this
      confirmatory assay using DBS when a lack of adequate infrastructure to collect,
      store or transport plasma/serum is found. DBS are a practical alternative to
      plasma/serum for HIV serological diagnosis.

PMID- 25600610
TI  - Clinical and molecular characterization of rhinoviruses A, B, and C in adult
      patients with pneumonia.
AB  - BACKGROUND: Human rhinoviruses (HRVs) have increasingly been reported to be
      associated with lower respiratory tract infections. HRV-C has been associated
      with more severe respiratory illnesses in children. OBJECTIVES: We investigated
      the clinical and molecular characteristics of HRV-A, HRV-B, and HRV-C in adults
      with pneumonia. STUDY DESIGN: HRV genotyping and quantitative real-time reverse
      transcriptase polymerase chain reaction were performed on 392 adult respiratory
      specimens consecutively collected from June 2012 to May 2013. Pneumonia was
      identified by review of medical records and chest radiographs. RESULTS: Adult
      patients with pneumonia and identified HRV genotypes (n=165) were included. HRV
      A, HRV-B, and HRV-C were identified in 97, 28, and 40 patients, respectively. No
      differences in underlying diseases, APACHE II score, or frequency of co-infection
      were observed between the HRV species. Compared with HRV-A, HRV-B was more often
      associated with neutropenia (21.4% vs. 7.2%, p=0.07), hospital acquisition (32.1%
      vs. 7.2%, p=0.048), and fever (78.6% vs. 49.3%, p=0.003). Mean viral load
      (copies/ml) was lower for HRV-B (10(2.6) vs. 10(4.1) in HRV-A and 10(4.3) in HRV
      C), and high viral loads (>=10(4)) occurred most frequently with HRV-C (70.0% vs.
      57.7% for HRV-A and 21.4% for HRV-B). The incidence of severe pneumonia was
      similar for HRV-A (18.6%), HRV-B (21.4%), and HRV-C (20.0%), and in-hospital
      mortality rates did not differ significantly (15.5%, 10.7%, and 12.5%,
      respectively). CONCLUSIONS: In contrast to previous pediatric studies, no
      differences were observed in clinical severity or outcomes between the different
      HRV species in adult patients with pneumonia.

PMID- 25600611
TI  - HEV infection in two referral centers in Spain: epidemiology and clinical
      outcomes.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is one of the major causes of
      icteric hepatitis worldwide. In industrialized countries it is considered an
      emerging disease, as a growing number of autochthonous cases have been reported
      in recent years. Occasional extrahepatic manifestations have been described in
      the setting of HEV infection. STUDY DESIGN: To characterize the epidemiological
      pattern and clinical outcomes of new cases of HEV infection diagnosed in two
      referral centers during the period 2011-2013. RESULTS: During the study period,
      four cases of self-limited acute hepatitis E after travel to endemic areas were
      recorded, as well as five cases of HEV infection after solid organ
      transplantation. Four patients failed to spontaneously clear the virus and
      received ribavirin monotherapy; all of them had HEV genotype-3. Ribavirin was
      effective in inhibiting HEV replication, although in one patient a virological
      relapse occurred after the end of therapy. Finally, we report a case of HEV
      genotype-3 related agranulocytosis in an immunocompetent patient, resulting in a
      fatal outcome; this is the first case reported of its kind. CONCLUSION: Diagnosis
      of HEV infection needs to be taken into consideration in patients with acute or
      chronic hepatitis in whom other etiologies have been excluded. Although
      hematological complications related to acute HEV infection are infrequent, these
      may affect any of the bone marrow series, even after viral clearance.

PMID- 25600612
TI  - Benzoxazinoids: Cereal phytochemicals with putative therapeutic and health
      protecting properties.
AB  - Benzoxazinoids (BXs) are a group of natural chemical compounds with putative
      pharmacological and health-protecting properties. BXs were formerly identified in
      and isolated from selected dicot medicinal plants and young cereal plants.
      Recently, BXs were found to be present in mature cereal grains and bakery
      products, such that knowledge about the pharmacological properties of BXs, which
      until now have unknowingly been consumed through the daily bread and breakfast
      cereals, has come into new focus. This review discusses published results from in
      vitro studies and a few human and animal model studies on the health effects and
      pharmacological responses of various BX compounds. Many of these studies have
      reported antimicrobial, anticancer, reproductive system stimulatory, central
      nervous system stimulatory, immunoregulatory, and appetite- and weight-reducing
      effects of BXs and/or BX derivatives. The health benefits of wholegrain intake
      may be associated with the solitary and/or overlapping biological effects of
      fibers, lignans, phenolic acids, alkylresorcinols, BXs, and other bioactive
      compounds. In the context of BXs as dietary ingredients, further comprehensive
      investigations are required to understand their biological functions, to
      elucidate the underlying mechanisms, to explore their potential contribution on
      the health effects associated with wholegrain consumption, and to examine their
      potential as functional food ingredients. 

PMID- 25600613
TI  - In vitro-in vivo extrapolations to evaluate the effect of concomitant drugs on
      tacrolimus (FK506) exposure.
AB  - The effect of concomitant drugs having a cytochrome P450 (CYP) 3A inhibitory
      potency on tacrolimus exposure was predicted from in vitro metabolism results. In
      this study, the IC50 values of concomitant drugs on the formation of M-I, the
      major metabolite of tacrolimus, were determined, and the effect on oral exposure
      (AUCp.o.) of tacrolimus was assessed from static models. When an absorbed
      fraction (Fa ) of 0.97, intestinal wall availability (Fg) of 0.27 and fraction
      metabolized by CYP3A (fm(CYP3A)) of 0.8 were used, the least bias was observed
      for the prediction of the AUCp.o. of tacrolimus. The relationship of the IC50
      values of 11 inhibitors between tacrolimus and typical CYP3A substrates
      (midazolam and testosterone) was also analysed. A strong correlation was found
      between the IC50 values of tacrolimus and typical CYP3A substrates (r(2)  >=
      0.85). The predictability of the effect of inhibitors on tacrolimus AUCp.o. was
      investigated based on the same static models with the use of published IC50
      values for midazolam and testosterone. The bias for the prediction of tacrolimus
      AUCp.o. was minimal with the use of IC50 values determined using tacrolimus
      itself as a substrate. These results suggest that tacrolimus itself is still the
      best choice for predicting the AUCp.o. of tacrolimus, although our findings
      suggest that midazolam or testosterone may be used instead of tacrolimus to
      estimate roughly (predicted AUCp.o. within an approximately 2-fold range of
      observed values) the effect of CYP3A inhibitors on the tacrolimus AUCp.o.

PMID- 25600615
TI  - Duodenal gangliocytic paraganglioma: A case report and literature review.
AB  - INTRODUCTION: Gangliocytic paraganglioma is a rare tumor that is most commonly
      located in the duodenum. At presentation, it may be confused with a
      gastrointestinal stromal tumor (GIST), but distinguishing between these tumors is
      critical because the natural history and treatment of these two tumors differs
      markedly. Duodenal gangliocytic paraganglioma typically exhibits benign behavior
      with occasional regional lymph node metastasis and no reports of tumor associated
      deaths. Recurrence after resection is rare. PRESENTATION OF CASE: A 50 year-old
      male presented with melena and hemoglobin concentration of 4.6g/dl.
      Esophagogastroduodenoscopy demonstrated a submucosal mass in the third portion of
      the duodenum with no active bleeding. CT scan identified no regional
      lymphadenopathy or distant metastasis. The tumor was resected through a
      longitudinal duodenotomy with negative margins. DISCUSSION: Endoscopic resection
      of duodenal gangliocytic paraganglioma appears to be safe and effective when
      tumor may be removed in its entirety by this method. If the tumor is not
      suspended by a stalk or there is suspicion for regional lymph node disease then
      surgical management is preferred. Radiation oncologists at high volume centers
      have endorsed utilization of adjuvant radiotherapy to the postsurgical bed in
      cases involving lymph node metastasis. Utilization of chemotherapy for management
      of this disease has not been reported. CONCLUSION: Localized duodenal
      gangliocytic paragangliomas are best managed by resection with negative margins.
      In cases in which the tumor is resected with negative margins, it appears to be
      safe to embark on a course of surveillance and forego adjuvant therapy.

PMID- 25600614
TI  - InGaP 670-nm laser therapy combined with a hydroalcoholic extract of Solidago
      chilensis Meyen in burn injuries.
AB  - Therapies that accelerate the healing of burn injuries, improving the quality of
      life of the patient and reducing the cost of treatment are important. This study
      evaluated the effects of InGaP 670-nm laser therapy combined with a
      hydroalcoholic extract of Solidago chilensis leaves on burn wound healing in
      rats. Seventy-two rats were divided randomly into four groups: control untreated
      (C), treated with InGaP 670-nm laser with power density of 0.41 W/cm(2) and
      energy density of 4.93 J/cm(2) (L), treated with S. chilensis extract (S) and
      treated with S. chilensis extract and laser (LS). Second-degree burns were
      produced on the back of the animals with metal plate. Wound samples were
      collected on days 7, 14 and 21 of treatment for structural analysis, morphometry
      and Western blotting to quantify the expression of transforming growth factor
      beta 1 (TGF-beta1) and vascular endothelial growth factor (VEGF). The results
      showed that InGaP laser irradiation at 670 nm alone and combined with extract of
      S. chilensis promoted significant tissue repair responses in this experimental
      model, increasing the number of fibroblasts, collagen fibres and newly formed
      blood vessels throughout the experimental period and decreasing the number of
      granulocytes in burn wounds of second degree in all treated groups. Exclusive
      treatment of burn wounds with the hydroalcoholic extract of S. chilensis provided
      similar quantitative results to those seen in the untreated group throughout the
      experimental period. Therefore, it was observed in the L and LS groups different
      responses in the expression of TGF-beta1 and VEGF. The application of 670-nm
      laser alone or combined with the extract of S. chilensis promoted favourable
      responses in tissue repair of second-degree burns in this experimental model.

PMID- 25600616
TI  - Propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the
      PPARgamma/LXRalpha signaling pathway in THP-1 macrophage-derived foam cells.
AB  - BACKGROUND: ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette
      transporter G1 (ABCG1), and scavenger receptor-B1 (SR-B1) promote cholesterol
      efflux from cells to lipid-poor apolipoprotein A-I and play an important role in
      the development of atherosclerosis. Liver X receptor (LXRalpha) and peroxisome
      proliferator-activated receptor-gamma (PPARgamma) operate as cholesterol sensors,
      which may protect from cholesterol overload by stimulating cholesterol efflux
      from cells to high-density lipoprotein through ABCA1, ABCG1, and SR-B1. Propofol
      administration is associated with cardiovascular protective effects, including
      anti-inflammatory and antioxidant properties. Here, we examined the effect of
      propofol on ABCA1, ABCG1, and SR-B1 expression and explored whether PPARgamma and
      LXRalpha were involved in the regulation of propofol-induced ABCA1, ABCG1, and SR
      B1 expression in THP-1 macrophage-derived foam cells. METHODS AND RESULTS:
      Propofol significantly increased expression levels of ABCA1, ABCG1, and SR-B1 in
      a time-dependent manner. Cellular cholesterol content was decreased while
      cholesterol efflux was increased by propofol treatment. Moreover, PPARgamma and
      LXRalpha were up-regulated by propofol treatment. In addition, the up-regulated
      expression of ABCA1, ABCG1, and SR-B1 by propofol was significantly abolished by
      both PPARgamma siRNA and LXRalpha siRNA in THP-1 macrophage-derived foam cells.
      CONCLUSION: These results provide evidence that propofol up-regulates expression
      of ABCA1, ABCG1, and SR-B1 through the PPARgamma/LXRalpha pathway in THP-1
      macrophage-derived foam cells.

PMID- 25600617
TI  - The generation of continuous-variable entanglement frequency comb.
AB  - Continuous-variable (CV) entanglement frequency comb can be produced by enhanced
      Raman scattering in an above-threshold optical oscillator cavity in which a
      hexagonally-poled LiTaO3 crystal resides as a Raman gain medium. The Stokes and
      anti-Stokes Raman signals are enhanced by a coupled quasi-phase-matching optical
      parametric process and the entanglement natures among these Raman signals and
      pump are demonstrated by applying a sufficient inseparability criterion for CV
      entanglement. Such entanglement frequency comb source with different frequencies
      and continuously tunable frequency interval may be very significant for the
      applications in quantum communication and networks. 

PMID- 25600618
TI  - Controlled growth of immunogold for amplified optical detection of aflatoxin B1.
AB  - A simple, sensitive and cost-effective method for the analysis of the mycotoxin
      aflatoxin B1 (AFB1) has been established based on controlled growth of
      immunogold. AFB1-BSA conjugate modified magnetic beads were employed as capture
      probe and anti-AFB1 antibody-coated gold colloids were used as detection probe
      for the immunological recognition of AFB1, as well as for signal transduction.
      The immune recognition event is converted into the gold enlargement signal which
      can be quantitatively measured by UV-vis spectroscopy. The autocatalytic
      enlargement of immunogold was conducted in aqueous solution containing
      chloroauric acid, hexadecyltrimethylammonium bromide and ascorbic acid. The
      reaction could be stopped by the addition of sodium thiosulfate. The final
      absorbance and resonance light scattering intensity were highly dependent on
      immunogold concentration. After gold enhancement, the sensitivity of the
      immunoassay was improved and total assay time reduced to 1 h. Under optimized
      conditions, the linear range and lower detection limit was 0.01-1 ng mL(-1) and 7
      pg mL(-1), respectively. The proposed method offers great promise for sensitive
      detection of other mycotoxins and organic pollutants. 

PMID- 25600619
TI  - Comparison of the hemodynamic response to induction and intubation during a
      target-controlled infusion of propofol with 2 different pharmacokinetic models. A
      prospective ramdomized trial.
AB  - OBJECTIVE: Determine the best propofol pharmacokinetic model that meets patient
      requirements and is devoid of major haemodynamic side effects. MATERIAL AND
      METHODS: Prospective, randomised, open-label, clinical trial was performed on an
      intention to treat basis. It included 280 patients with ASA physical status i
      iii, aged 18 to 80 years and weight range between 45 to 100kg, scheduled for
      surgery under general anaesthesia. They were randomized into 2 groups according
      to the pharmacokinetic model: Modified Marsh group and Schnider group. The
      haemodynamic changes that occurred during the induction and intubation were
      analysed. A propofol target controlled infusion was started to achieve and
      maintain a bispectral index value between 35 and 55. At minute 6, orotracheal
      intubation was performed and the study finished at minute 11. Heart rate, mean
      arterial pressure and their product (HR*MAP) were measured and recorded every
      minute throughout the study. Every HR*MAP value was compared to its baseline
      value to determine the minimum value before intubation, the maximum value after
      intubation, the maximum variation after intubation, and its final value. The
      GRADIENTE (MIN, MAX) variable (primary endpoint of this study) analyses the
      difference between maximal and minimal values related to intubation. Propofol
      doses and calculated concentrations and any hypotensive events were also
      recorded. RESULTS: No differences were found between groups regarding
      haemodynamic performance. GRADIENTE (MIN, MAX) values and the percentage of
      hypotensive events were: Modified Marsh group median 77.41% vs. Schnider group
      84.86% (p= 0.821) and 17.3% vs. 12.8% (p = 0.292), respectively. CONCLUSION: The
      study failed to demonstrate any haemodynamic difference between the 2 groups,
      even though the Modified Marsh group received a larger dose of propofol.

PMID- 25600620
TI  - [Influence of the type of anesthesia and the level of urgency in post-surgical
      pain after a cesarian].

PMID- 25600621
TI  - Engineering the ligninolytic enzyme consortium.
AB  - The ligninolytic enzyme consortium is one of the most-efficient oxidative systems
      found in nature, playing a pivotal role during wood decay and coal formation.
      Typically formed by high redox-potential oxidoreductases, this array of enzymes
      can be used within the emerging lignocellulose biorefineries in processes that
      range from the production of bioenergy to that of biomaterials. To ensure that
      these versatile enzymes meet industry standards and needs, they have been
      subjected to directed evolution and hybrid approaches that surpass the limits
      imposed by nature. This Opinion article analyzes recent achievements in this
      field, including the incipient groundbreaking research into the evolution of
      resurrected enzymes, and the engineering of ligninolytic secretomes to create
      consolidated bioprocessing microbes with synthetic biology applications. 

PMID- 25600622
TI  - Genome editing-based HIV therapies.
AB  - Genome editing (GE)-based HIV therapy is achieved by modification of infection
      related genes to produce HIV-resistant cells followed by reinfusion of the
      modified cells into patients. The ultimate goal is to achieve a functional or
      actual cure for HIV infection. Despite multiple potential targets for GE-based
      HIV therapies, CCR5 is the most feasible owing to the naturally existing CCR5
      delta32 genotype which confers resistance to HIV. A recent clinical trial of
      infusion of modified autologous CD4(+) T cells proved safety and efficacy within
      the limits of the studies. However, long-term evaluation of the safety and
      efficacy is required before GE-based HIV therapy is ready for clinical
      implementation. 

PMID- 25600623
TI  - Effect of acute ammonia exposure on expression of GH/IGF axis genes GHR1, GHR2
      and IGF-1 in pufferfish (Takifugu obscurus).
AB  - Waterborne ammonia has become a persistent pollutant of aquatic habitats. The
      exposure to ammonia stress can reduce growth in a wide range of aquatic
      organisms. To assess the effect of ammonia exposure on the growth hormone/insulin
      like growth factors (GH/IGF) axis, we identified and characterized GHR1, GHR2 and
      IGF-1 from pufferfish. Comparative analysis showed that these genes shared high
      identity and similarity with corresponding genes in other fish species. The
      transcripts of these genes were widely expressed in all tested tissues. The
      highest level of GHR1 mRNA was found in the brain, whereas GHR2 and IGF-1 mRNA
      levels were the highest in the liver. Following acute ammonia exposure (100 mg/L
      total ammonia-nitrogen), GHR2 expression in the liver did not change at 6 h and
      then significantly decreased at 12, 24 and 48 h, whereas GHR1 and IGF-1
      expressions were significantly down-regulated at 6, 12, 24 and 48 h,
      respectively. These results indicated that ammonia stress decreased the
      expression of GH/IGF axis genes, which might have negative effect on the growth
      and development of pufferfish.

PMID- 25600624
TI  - Ulnar Neuropathy Among Active Workers Based Upon Hand Diagram Ratings.
AB  - BACKGROUND: Limited studies have estimated the prevalence of ulnar neuropathy
      (UN) in the workplace. Hand diagrams have been demonstrated to have a good
      sensitivity and specificity when attempting to identify patients with UN.
      OBJECTIVE: To determine the prevalence and associated risk factors for UN among
      active workers based on results of a hand diagram, and to determine the
      reliability of hand diagram scoring. DESIGN: Cross-sectional study. SETTING:
      Seven different industrial and clerical work sites. METHODS: A total of 501
      active workers were screened. Subjects completed a hand diagram and the Job
      Content Questionnaire, and had ergonomic assessment of their job. Each hand
      diagram was scored independently by 2 raters. MAIN OUTCOME MEASURES: Rating of
      the hand diagram for UN. RESULTS: Interrater reliability of scoring the hand
      diagram for UN was very high. The estimated prevalence of UN was 3.6%. Suspected
      UN was associated with positioning of the elbow but not by contact stress at the
      elbow or force at the hand. Smokers had a lower prevalence, but smokers with
      suspected UN had higher-pack year histories. Workers with suspected UN had a
      greater sense of job insecurity and lower job satisfaction rating. CONCLUSIONS:
      Hand diagram rating has a high interrater reliability. Suspected UN has a
      relatively high prevalence among active workers in comparison to prior estimates
      of the prevalence of UN among the general population and is not strongly
      associated with ergonomic factors.

PMID- 25600625
TI  - Hamstring Elongation Quantified Using Ultrasonography During the Straight Leg
      Raise Test in Individuals With Low Back Pain.
AB  - BACKGROUND: Although the straight leg raise (SLR) test frequently is used to
      assess hamstring extensibility in individuals with low back pain (LBP), evidence
      relating LBP, SLR, and hamstring extensibility remains unclear. The SLR measures
      the angle between the lifted leg and the horizontal, however, and, as such, it is
      not a direct measure of the elongation capacity of the hamstrings. OBJECTIVE: To
      examine the differences in hamstring elongation (quantified via ultrasonography)
      and SLR score between individuals with LBP and asymptomatic controls and to
      determine the relationship between hamstring elongation, SLR, and functional
      disability scores. DESIGN: Cross-sectional study. SETTING: University laboratory.
      PARTICIPANTS: Forty men and women with chronic LBP (mean +/- SD, age 43.51 +/-
      3.71 years and 40 control subjects (age 45.11 +/- 4.01 years) participated in
      this study. ASSESSMENT: Passive SLR, elongation assessed via ultrasonography, and
      functional disability. ASSESSMENT AND OUTCOME MEASUREMENTS: SLR score, elongation
      of tendinous tissue within the semitendinosus muscle, and Oswestry Disability
      Index. RESULTS: Two-way analysis of variance tests indicated a significantly
      lower SLR score and a greater Oswestry score in LBP group compared with control
      subjects (P < .05). In contrast, there were no significant group differences in
      hamstring elongation (P > .05). Gender did not have an effect on all dependent
      measures (P > .05). Hamstring elongation showed a low correlation with SLR score
      and a minimal correlation with Oswestry score. CONCLUSIONS: These results
      indicate that the SLR score is not determined by hamstring elongation (quantified
      via ultrasonography).

PMID- 25600626
TI  - Expression of citrulline and homocitrulline residues in the lungs of non-smokers
      and smokers: implications for autoimmunity in rheumatoid arthritis.
AB  - INTRODUCTION: Smoking is a well-established risk factor for rheumatoid arthritis
      (RA), and it has been proposed that smoking-induced citrullination renders
      autoantigens immunogenic. To investigate this mechanism, we examined human lung
      tissue from 40 subjects with defined smoking status, with or without chronic
      obstructive pulmonary disease (COPD), and control tissues from other organs for
      citrullinated proteins and the deiminating enzymes peptidylarginine deiminase
      type-2 (PAD2) and -4 (PAD4). METHODS: Lung tissue samples, dissected from
      lobectomy specimens from 10 never smokers, 10 smokers without airflow limitation,
      13 COPD smokers and eight COPD ex-smokers, and control tissue samples (spleen,
      skeletal muscle, liver, ovary, lymph node, kidney and heart), were analysed for
      citrullinated proteins, PAD2 and PAD4 by immunoblotting. Citrulline and
      homocitrulline residues in enolase and vimentin were analysed by partial
      purification by gel electrophoresis followed by mass spectrometry in 12 of the
      lung samples and one from each control tissues. Band intensities were scored semi
      quantitatively and analysed by two-tailed Mann-Whitney T-test. RESULTS: Within
      the lung tissue samples, citrullinated proteins, PAD2 and PAD4 were found in all
      samples, with an increase in citrullination in COPD (P = 0.039), but minimal
      difference between smokers and non-smokers (P = 0.77). Citrullination was also
      detected at lower levels in the tissues from other organs, principally in lymph
      node, kidney and skeletal muscle. Mass spectrometry of the lung samples showed
      that vimentin was citrullinated at positions 71, 304, 346, 410 and 450 in non
      smokers and smokers both with and without COPD. A homocitrulline at position 104
      was found in four out of six COPD samples and one out of six non-COPD. Citrulline
      450 was also found in three of the control tissues. There were no citrulline or
      homocitrulline residues demonstrated in alpha-enolase. CONCLUSIONS: We have shown
      evidence of citrullination of vimentin, a major autoantigen in RA, in both non
      smokers and smokers. The increase in citrullinated proteins in COPD suggests that
      citrullination in the lungs of smokers is mainly due to inflammation. The
      ubiquity of citrullination of vimentin in the lungs and other tissues suggests
      that the relationship between smoking and autoimmunity in RA may be more complex
      than previously thought.

PMID- 25600627
TI  - Conditions for seeding and promoting neo-auricular cartilage formation in a
      fibrous collagen scaffold.
AB  - BACKGROUND: Carved autologous costal cartilage and porous polyethylene implants
      (Medpor) are the most common approaches for total ear reconstruction, but these
      approaches may have inconsistent cosmetic outcomes, a high risk of extrusion, or
      other surgical complications. Engineering ear cartilage to emulate native
      auricular tissue is an appealing approach, but often the cell-seeded scaffolds
      are susceptible to shrinkage and architectural changes when placed in vivo. The
      aim of this study was to assess the most favorable conditions for in vitro pre
      culture of cell-seeded type I collagen scaffolds prior to in vivo implantation.
      METHODS: Sheep auricular chondrocytes were seeded into this type I collagen
      scaffold. The cell-seeded constructs were cultured in either static or dynamic
      conditions for two days or two weeks and then implanted into nude mice for
      another six weeks. The harvested constructs were evaluated histologically,
      immunohistochemically, and biochemically. RESULTS: Robust neo-cartilage formation
      was found in these collagen scaffolds seeded with auricular chondrocytes, which
      was comparable to native cartilage morphologically, histologically, and
      biochemically. Culture under dynamic conditions prior to implantation improved
      the neo-cartilage formation histologically and biochemically. CONCLUSION: Dynamic
      culture of this cell-seeded fibrous collagen material could permit predictable
      engineered auricular cartilage and a promising approach for external ear
      reconstruction.

PMID- 25600628
TI  - Facial nerve injuries associated with the retromandibular transparotid approach
      for reduction and fixation of mandibular condyle fractures.
AB  - PURPOSE: To document facial nerve (FN) injuries after surgical treatment of
      mandibular condylar fractures using the retromandibular transparotid approach and
      to identify risk factors associated with these injuries. MATERIALS AND METHODS: A
      retrospective study of patients surgically treated for mandibular condylar
      fractures using the retromandibular transparotid approach over seven years was
      conducted. The primary study variable was the postoperative change in FN function
      after fracture fixation. Risk factors were categorized as demographic, anatomic,
      experience of the operator, fracture displacement/dislocation and number of
      miniplates placed at the fracture site. Appropriate statistics were computed.
      RESULTS: Ninety patients with 102 fractures were analysed. Thirty two fractures
      (31%) were located in the condylar neck and 70 fractures (69%) were subcondylar
      (located below the sigmoid notch). The condylar segment was undisplaced in twelve
      cases (12%), displaced medially in thirty five (34%), laterally displaced in
      thirty (29%) and dislocated in 25 (24.5%). In 18 fractures (18%), postoperative
      examination revealed various degrees of damage to the FN. All nerve injuries
      recovered completely in 8-24 weeks. In a multivariate model, condylar neck
      fractures, fracture dislocation and operator inexperience were associated with a
      statistically significant risk of postoperative deterioration of FN function (P
      <= 0.05). CONCLUSION: The majority of facial nerve injuries after surgical
      treatment of condylar fractures by the retromandibular transparotid approach are
      transient in nature. Condylar neck fractures, fracture dislocation and operator
      inexperience were associated with an increased risk for FN injury.

PMID- 25600629
TI  - Skeletal and soft tissue changes and stability in cleft lip and palate patients
      after distraction osteogenesis using a new intraoral maxillary device.
AB  - BACKGROUND: The authors have recently reported on the use of an internal
      maxillary distraction device. In this study, we report on the hard and soft
      tissue movements achieved with this intraoral distraction device, and the
      stability changes after distraction osteogenesis for maxillary hypoplasia in
      patients with cleft lip and palate. METHODS: Ten male patients with severe
      hypoplasia of the maxilla, with complete uni- or bilateral cleft lip and palate
      were included. The mean age of the patients at the time of operation was 11.91
      years (+/-3.41). To evaluate the distraction process and stability,
      superimpositions on the preoperative lateral cephalograms were performed. The
      mean follow-up (FU) was 15.42 months (+/-3.94). RESULTS: Cephalometric
      measurements at all of the maxillary hard and soft tissue points improved
      significantly. Maxillary point A was advanced by 8.25 mm (+/-3.17; P < 0.001).
      After distraction soft tissue point A' had advanced 7.10 mm (+/-2.69; P < 0.001).
      The soft tissue to hard tissue ratio at point A was 0.86:1 after distraction.
      Maxillary horizontal relapse at point A was 14.1% at FU. Vertical relapse was not
      significant. CONCLUSION: This rigid intraoral distraction device can be
      successfully used in the correction of severe maxillary hypoplasia. The marked
      aesthetic improvement and low psychological encumbrance make this device viable
      for the treatment of cleft-related hypoplasia of the maxilla.

PMID- 25600630
TI  - Treatment selection for patients with ductal carcinoma in situ (DCIS) of the
      breast using the University of Southern California/Van Nuys (USC/VNPI) prognostic
      index.
AB  - The University of Southern California/Van Nuys Prognostic Index (USC/VNPI) is an
      algorithm that quantifies five measurable prognostic factors known to be
      important in predicting local recurrence in conservatively treated patients with
      ductal carcinoma in situ (DCIS) (tumor size, margin width, nuclear grade, age,
      and comedonecrosis). With five times as many patients since originally developed,
      sufficient numbers now exist for analysis by individual scores rather than groups
      of scores. To achieve a local recurrence rate of less than 20% at 12 years, these
      data support excision alone for all patients scoring 4, 5, or 6 and patients who
      score 7 but have margin widths >=3 mm. Excision plus RT achieves the less than
      20% local recurrence threshold at 12 years for patients who score 7 and have
      margins <3 mm, patients who score 8 and have margins >=3 mm, and for patients who
      score 9 and have margins >=5 mm. Mastectomy is required for patients who score 8
      and have margins <3 mm, who score 9 and have margins <5 mm and for all patients
      who score 10, 11, or 12 to keep the local recurrence rate less than 20% at 12
      years. DCIS is a highly favorable disease. There is no difference in mortality
      rate regardless of which treatment is chosen. The USC/VNPI is a numeric tool that
      can be used to aid the treatment decision-making process.

PMID- 25600631
TI  - Extensive simulations of the full-length matrix metalloproteinase-2 enzyme in a
      prereactive complex with a collagen triple-helical peptide.
AB  - Collagen hydrolysis catalyzed by matrix metalloproteinases is an important and
      complex process involved in a variety of physiological and pathological
      conditions. To contribute to its characterization at the molecular level, herein
      we analyze three different models for the complex formed between the full-length
      matrix metalloproteinase-2 (MMP-2) enzyme and a synthetic triple-helical peptide
      (fTHP-5). The considered MMP-2/fTHP-5 complexes mainly differ in the location of
      the C-terminal hemopexin-like domain, but in all of them, the middle alpha-chain
      of the substrate (B-chain) is placed within the active site groove. We performed
      extended molecular dynamics (MD) simulations to determine the most likely
      rearrangements of the MMP-2 domains in response to the presence of the triple
      helix. The relative stability of the MD models is assessed in terms of molecular
      mechanics Poisson-Boltzmann calculations and approximate estimations of
      configurational entropy. In addition, the most significant MMP-2...fTHP-5
      interactions at the catalytic and noncatalytic domains are also analyzed to
      gather some clues about the role of the different domains during collagenolysis. 

PMID- 25600632
TI  - Non-canonical WNT5A is a potential regulator of granulosa cell function in
      cattle.
AB  - The WNT family has been implicated in follicular development in rodents, however,
      the role of WNTs in the follicle of monovulatory species is poorly understood.
      The objective of this study was to determine the potential roles of WNTs in
      bovine granulosa cell function. Cells cultured in serum-free medium expressed
      mRNA encoding WNT2B, WNT5B and WNT5A. Levels of WNT5A, but not of WNT2B or WNT5B
      mRNA, were down-regulated by FSH. Addition of WNT5A to cultured cells suppressed
      FSH-stimulated estradiol and progesterone secretion, and levels of mRNA encoding
      the steroidogenic enzymes CYP19A1, CYP11A1 and the FSH receptor, but had no
      effect on cell proliferation or apoptosis. Immunoblot experiments showed that
      WNT5A reduced activation of CTNNB1 and stimulated phosphorylation of MAPK8 and
      JUN proteins. We conclude that WNT5A is a negative regulator of FSH-stimulated
      granulosa cell steroidogenesis, and that it acts by suppressing canonical WNT
      signaling activity and inducing the non-canonical MAPK8/JUN pathway. 

PMID- 25600634
TI  - Occipital TMS at phosphene detection threshold captures attention automatically.
AB  - Strong stimuli may capture attention automatically, suggesting that attentional
      selection is determined primarily by physical stimulus properties. The mechanisms
      underlying capture remain controversial, in particular, whether feedforward
      subcortical processes are its main source. Also, it remains unclear whether only
      physical stimulus properties determine capture strength. Here, we demonstrate
      strong capture in the absence of feedforward input to subcortical structures such
      as the superior colliculus, by using transcranial magnetic stimulation (TMS) over
      occipital visual cortex as an attention cue. This implies that the feedforward
      sweep through subcortex is not necessary for capture to occur but rather provides
      an additional source of capture. Furthermore, seen cues captured attention more
      strongly than (physically identical) unseen cues, suggesting that the momentary
      state of the nervous system modulates attentional selection. In summary, we
      demonstrate the existence of several sources of attentional capture, and that
      both physical stimulus properties and the state of the nervous system influence
      capture. 

PMID- 25600633
TI  - A kernel machine method for detecting effects of interaction between
      multidimensional variable sets: an imaging genetics application.
AB  - Measurements derived from neuroimaging data can serve as markers of disease
      and/or healthy development, are largely heritable, and have been increasingly
      utilized as (intermediate) phenotypes in genetic association studies. To date,
      imaging genetic studies have mostly focused on discovering isolated genetic
      effects, typically ignoring potential interactions with non-genetic variables
      such as disease risk factors, environmental exposures, and epigenetic markers.
      However, identifying significant interaction effects is critical for revealing
      the true relationship between genetic and phenotypic variables, and shedding
      light on disease mechanisms. In this paper, we present a general kernel machine
      based method for detecting effects of the interaction between multidimensional
      variable sets. This method can model the joint and epistatic effect of a
      collection of single nucleotide polymorphisms (SNPs), accommodate multiple
      factors that potentially moderate genetic influences, and test for nonlinear
      interactions between sets of variables in a flexible framework. As a
      demonstration of application, we applied the method to the data from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) to detect the effects of the
      interactions between candidate Alzheimer's disease (AD) risk genes and a
      collection of cardiovascular disease (CVD) risk factors, on hippocampal volume
      measurements derived from structural brain magnetic resonance imaging (MRI)
      scans. Our method identified that two genes, CR1 and EPHA1, demonstrate
      significant interactions with CVD risk factors on hippocampal volume, suggesting
      that CR1 and EPHA1 may play a role in influencing AD-related neurodegeneration in
      the presence of CVD risks. 

PMID- 25600635
TI  - Barriers over time to full implementation of health information exchange in the
      United States.
AB  - BACKGROUND: Although health information exchanges (HIE) have existed since their
      introduction by President Bush in his 2004 State of the Union Address, and
      despite monetary incentives earmarked in 2009 by the health information
      technology for economic and clinical health (HITECH) Act, adoption of HIE has
      been sparse in the United States. Research has been conducted to explore the
      concept of HIE and its benefit to patients, but viable business plans for their
      existence are rare, and so far, no research has been conducted on the dynamic
      nature of barriers over time. OBJECTIVE: The aim of this study is to map the
      barriers mentioned in the literature to illustrate the effect, if any, of
      barriers discussed with respect to the HITECH Act from 2009 to the early months
      of 2014. METHODS: We conducted a systematic literature review from CINAHL,
      PubMed, and Google Scholar. The search criteria primarily focused on studies.
      Each article was read by at least two of the authors, and a final set was
      established for evaluation (n=28). RESULTS: The 28 articles identified 16
      barriers. Cost and efficiency/workflow were identified 15% and 13% of all
      instances of barriers mentioned in literature, respectively. The years 2010 and
      2011 were the most plentiful years when barriers were discussed, with 75% and 69%
      of all barriers listed, respectively. CONCLUSIONS: The frequency of barriers
      mentioned in literature demonstrates the mindfulness of users, developers, and
      both local and national government. The broad conclusion is that public policy
      masks the effects of some barriers, while revealing others. However, a
      deleterious effect can be inferred when the public funds are exhausted. Public
      policy will need to lever incentives to overcome many of the barriers such as
      cost and impediments to competition. Process improvement managers need to
      optimize the efficiency of current practices at the point of care. Developers
      will need to work with users to ensure tools that use HIE resources work into
      existing workflows.

PMID- 25600637
TI  - Evolutionary change in testes tissue composition among experimental populations
      of house mice.
AB  - Theory assumes that postcopulatory sexual selection favors increased investment
      in testes size because greater numbers of sperm within the ejaculate increase the
      chance of success in sperm competition, and larger testes are able to produce
      more sperm. However, changes in the organization of the testes tissue may also
      affect sperm production rates. Indeed, recent comparative analyses suggest that
      sperm competition selects for greater proportions of sperm-producing tissue
      within the testes. Here, we explicitly test this hypothesis using the powerful
      technique of experimental evolution. We allowed house mice (Mus domesticus) to
      evolve via monogamy or polygamy in six replicate populations across 24
      generations. We then used histology and image analysis to quantify the proportion
      of sperm-producing tissue (seminiferous tubules) within the testes of males. Our
      results show that males that had evolved with sperm competition had testes with a
      higher proportion of seminiferous tubules compared with males that had evolved
      under monogamy. Previously, it had been shown that males from the polygamous
      populations produced greater numbers of sperm in the absence of changes in testes
      size. We thus provide evidence that sperm competition selects for an increase in
      the density of sperm-producing tissue, and consequently increased testicular
      efficiency. 

PMID- 25600636
TI  - Cancer systems biology of TCGA SKCM: efficient detection of genomic drivers in
      melanoma.
AB  - We characterized the mutational landscape of human skin cutaneous melanoma (SKCM)
      using data obtained from The Cancer Genome Atlas (TCGA) project. We analyzed next
      generation sequencing data of somatic copy number alterations and somatic
      mutations in 303 metastatic melanomas. We were able to confirm preeminent drivers
      of melanoma as well as identify new melanoma genes. The TCGA SKCM study confirmed
      a dominance of somatic BRAF mutations in 50% of patients. The mutational burden
      of melanoma patients is an order of magnitude higher than of other TCGA cohorts.
      A multi-step filter enriched somatic mutations while accounting for recurrence,
      conservation, and basal rate. Thus, this filter can serve as a paradigm for
      analysis of genome-wide next-generation sequencing data of large cohorts with a
      high mutational burden. Analysis of TCGA melanoma data using such a multi-step
      filter discovered novel and statistically significant potential melanoma driver
      genes. In the context of the Pan-Cancer study we report a detailed analysis of
      the mutational landscape of BRAF and other drivers across cancer tissues.
      Integrated analysis of somatic mutations, somatic copy number alterations, low
      pass copy numbers, and gene expression of the melanogenesis pathway shows
      coordination of proliferative events by Gs-protein and cyclin signaling at a
      systems level. 

PMID- 25600638
TI  - The accuracy of magnetic resonance imaging (MRI) in predicting the invasion of
      the tunica albuginea and the urethra during the primary staging of penile cancer.
AB  - OBJECTIVES: To assess the accuracy of magnetic resonance imaging (MRI) in
      predicting invasion of the tunica albuginea (TA) and the urethra during the
      primary staging of penile cancer. PATIENTS AND METHODS: In all, 104 consecutive
      patients with clinical T1-T3 penile cancer had a penile MRI as a part of local
      staging protocol. An artificial erection was induced before MRI by injecting
      alprostadil (prostaglandin E1 ). Four men with poor quality MRI images were
      excluded from the study. The preoperative MRI was compared with final histology
      to assess its accuracy in predicting the invasion of the TA and urethra. RESULTS:
      Data of 100 patients who underwent penile MRI before definitive surgery for
      invasive penile carcinoma were available for analysis. The mean age was 65 years
      and number of patients with pathological stage T1, T2 and T3 was 32, 52, and 16,
      respectively. The sensitivity and specificity of MRI in predicting the invasion
      of TA and urethra was 82.1% and 73.6%, and 62.5% and 82.1%, respectively. There
      were no MRI-related complications. CONCLUSIONS: This study shows that penile MRI
      is an accurate method for assessing TA invasion but is less sensitive in
      assessing urethral invasion. These results support the use of MRI in the local
      staging of penile cancer.

PMID- 25600640
TI  - Early significant ontogenetic changes in snake venoms.
AB  - Snake venom plays a critical role in food acquisition, digestion, and defense.
      Venoms are known to change throughout the life of some snake species, but nothing
      is known about the venom composition of hatchling/neonate snakes prior to and
      just after their first shedding cycle, despite this being a critical time in the
      life of the snake. Using a cohort of Crotalus horridus and two cohorts of
      Crotalus adamanteus, we showed for the first time that snakes undergo significant
      changes in venom composition after the postnatal shedding event. The number of
      changes among cohorts ranged widely and there was wide variation in the direction
      of protein regulation, which appeared to be on a locus-specific level rather than
      protein-family level. These significant venom composition changes that take place
      in the first few weeks of life most likely play critical roles in venom economy
      and resource conservation and may partially explain the rare, post-birth maternal
      care found in some venomous species. 

PMID- 25600641
TI  - Soluble expression and sodium channel activity of lt16a, a novel framework XVI
      conotoxin from the M-superfamily.
AB  - A peptide toxin, lt16a, from the venom of the worm-hunting Conus litteratus,
      shares the typical signal peptide sequences of M-superfamily conotoxins, which
      usually contain six cysteine residues that are arranged in a CC-C-C-CC pattern.
      Interestingly, lt16a comprises 21 amino acid residues in its mature region and
      has a cysteine framework XVI, which is arranged in a C-C-CC pattern. The coding
      region of lt16a was cloned into the pTRX vector and the fusion protein was
      overexpressed in Escherichia coli. After cleaving the fusion protein and
      purifying the protein lt16a using chromatography, the mass of lt16a was found by
      mass spectrometry to be consistent with the expected mass of 2357.7 Da. Whole
      cell patch clamp experiments demonstrated that lt16a could inhibit both the TTX
      sensitive and TTX-resistant sodium currents in adult rat dorsal root ganglion
      neurons. The inhibition of lt16a on TTX-resistant sodium currents was stronger
      than on TTX-sensitive sodium currents. To our knowledge, this is the first report
      of a framework XVI conotoxin that can inhibit voltage-gated sodium channel
      currents in mammalian sensory neurons. This report helps facilitates an
      understanding of the sequence diversity of conotoxins.

PMID- 25600642
TI  - Pattern of inflammatory response to Loxosceles intermedia venom in distinct mouse
      strains: a key element to understand skin lesions and dermonecrosis by poisoning.
AB  - Envenomation caused by spiders Loxosceles induce intense dermonecrosis at the
      bite site and systemic disease. In this work we described the hyaluronidase and
      collagenase activities in vitro of the Loxosceles intermedia venom, but no
      phospholipase A2 activity. In vivo, we evaluated the effect of L. intermedia
      venom used different strain of mice, C57BL/6, BALB/c and Swiss. All mice
      developed paw edema after venom injection, persistent for 24 h in BALB/c and
      C57BL/6 mice. Histopathological analysis of the skin after venom injection
      revealed vascular congestion in Swiss mice and an inflammatory reaction in BALB/c
      and C57BL/6 mice. The mobilization of inflammatory cells from bone marrow, spleen
      and blood was investigated. Typical innate immune response with mobilization of
      myeloid cells and cytotoxic CD8 T lymphocytes was observed in C57BL/6 mice. In
      contrast, typical acquired/humoral immune response was observed in BALB/c mice,
      with preferential involvement of conventional B lymphocytes and CD4 T helper
      cells. The skin inflammation associated to mobilization of inflammatory cells
      indicated that mice models are strongly recommended to investigate specific cell
      types involved with immune response to the envenomation and mechanisms to inhibit
      skin lesions. 

PMID- 25600643
TI  - The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into
      regulatory epigenetics in skeletal muscle stem cells.
AB  - Stem cells undergo a shift in metabolic substrate utilization during
      specification and/or differentiation, a process that has been termed metabolic
      reprogramming. Here, we report that during the transition from quiescence to
      proliferation, skeletal muscle stem cells experience a metabolic switch from
      fatty acid oxidation to glycolysis. This reprogramming of cellular metabolism
      decreases intracellular NAD(+) levels and the activity of the histone deacetylase
      SIRT1, leading to elevated H4K16 acetylation and activation of muscle gene
      transcription. Selective genetic ablation of the SIRT1 deacetylase domain in
      skeletal muscle results in increased H4K16 acetylation and deregulated activation
      of the myogenic program in SCs. Moreover, mice with muscle-specific inactivation
      of the SIRT1 deacetylase domain display reduced myofiber size, impaired muscle
      regeneration, and derepression of muscle developmental genes. Overall, these
      findings reveal how metabolic cues can be mechanistically translated into
      epigenetic modifications that regulate skeletal muscle stem cell biology. 

PMID- 25600644
TI  - Contact dermatitis as an adverse reaction to some topically used European herbal
      medicinal products - part 2: Echinacea purpurea-Lavandula angustifolia.
AB  - This review focuses on contact dermatitis as an adverse effect of a selection of
      topically used herbal medicinal products for which the European Medicines Agency
      has completed an evaluation up to the end of November 2013 and for which a
      Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench
      Lavandula angustifolia Mill. 

PMID- 25600646
TI  - TLR2 limits development of hepatocellular carcinoma by reducing IL18-mediated
      immunosuppression.
AB  - Immune mechanisms underlying hepatocellular carcinoma (HCC) are not well
      understood. Here, we show that the Toll-like receptor TLR2 inhibits production of
      the proinflammatory cytokine IL18 and protects mice from DEN-induced liver
      carcinogenesis. On this protocol, Tlr2(-/-) mice exhibited more aggressive HCC
      development associated with impaired CD8(+) T-cell function. Furthermore,
      Ly6C(high)IL18Ralpha(+) myeloid-derived suppressor cells (MDSC) were increased in
      number in the livers of Tlr2(-/-) mice before tumor onset. MDSC in this setting
      exhibited higher iNOS levels that could inhibit IFNgamma production and CD8(+) T
      cell proliferation in vitro. Notably, Tlr2(-/-) hepatocytes produced more mature
      IL18 after DEN treatment that was sufficient to drive MDSC accumulation there.
      IL18 administration was sufficient to induce accumulation of MDSC, whereas
      hepatocyte-specific silencing of IL18 in Tlr2(-/-) mice decreased the proportion
      of MDSC, increased the proportion of functional CD8(+) T cells, and alleviated
      HCC progression. IL18 production was mediated by caspase-8 insofar as the
      decrease in its silencing was sufficient to attenuate levels of mature IL18 in
      Tlr2(-/-) mice. Furthermore, the TLR2 agonist Pam3CSK4 inhibited both caspase-8
      and IL18 expression, decreasing MDSC, increasing CD8(+) T-cell function, and
      promoting HCC regression. Overall, our findings show how TLR2 deficiency
      accelerates IL18-mediated immunosuppression during liver carcinogenesis,
      providing new insights into immune control that may assist the design of
      effective immunotherapies to treat HCC.

PMID- 25600645
TI  - Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2
      and Interacts with miR-205.
AB  - Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and
      prognostic markers in several cancers, including renal cell carcinoma (RCC). In
      this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a
      specific focus on its transcriptional regulation and its interactions with Ezh2
      and miR-205. We found that MALAT1 expression was higher in human RCC tissues,
      where it was associated with reduced patient survival. MALAT1 silencing decreased
      RCC cell proliferation and invasion and increased apoptosis. Mechanistic
      investigations showed that MALAT1 was transcriptionally activated by c-Fos and
      that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was
      increased, whereas beta-catenin expression was decreased through Ezh2. Reciprocal
      interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound
      Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion,
      thereby blocking epithelial-mesenchymal transition via E-cadherin recovery and
      beta-catenin downregulation. Overall, our findings illuminate how overexpression
      of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic
      marker in this disease.

PMID- 25600648
TI  - Tumor-derived osteopontin reprograms normal mammary fibroblasts to promote
      inflammation and tumor growth in breast cancer.
AB  - Breast tumors are characterized by an extensive desmoplastic stroma, abundantly
      populated by fibroblasts. Cancer-associated fibroblasts (CAF) support
      tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and
      invasion. CAF also orchestrate tumor-promoting inflammation in multiple tumor
      types, including breast cancer. However, the mechanisms through which normal
      tissue fibroblasts are reprogrammed to tumor-promoting CAFs are mainly obscure.
      Here, we show that mammary fibroblasts can be educated by breast cancer cells to
      become activated to a proinflammatory state that supports malignant progression.
      Proteomic analysis of breast cancer cell-secreted factors identified the secreted
      proinflammatory mediator osteopontin, which has been implicated in inflammation,
      tumor progression, and metastasis. Osteopontin was highly secreted by mouse and
      human breast cancer cells, and tumor cell-secreted osteopontin activated a CAF
      phenotypes in normal mammary fibroblasts in vitro and in vivo. Osteopontin was
      sufficient to induce fibroblast reprogramming and neutralizing antibodies against
      osteopontin-blocked fibroblast activation induced by tumor cells. The ability of
      secreted osteopontin to activate mammary fibroblasts relied upon its known
      receptors CD44 and alphaVbeta3 integrin. Strikingly, osteopontin silencing in
      tumor cells in vivo attenuated stromal activation and inhibited tumor growth. Our
      findings establish a critical functional role for paracrine signaling by tumor
      derived osteopontin in reprograming normal fibroblasts into tumor-promoting CAFs.

PMID- 25600647
TI  - beta-arrestin-1 mediates nicotine-induced metastasis through E2F1 target genes
      that modulate epithelial-mesenchymal transition.
AB  - Cigarette smoking is a major risk factor in the development of non-small cell
      lung cancer (NSCLC), which accounts for 80% of all lung cancers. Nicotine, the
      major addictive component of tobacco smoke, can induce proliferation, invasion,
      and epithelial-to-mesenchymal transition (EMT) in NSCLC cell lines and promote
      metastasis of NSCLC in mice. Here, we demonstrate that the scaffolding protein
      beta-arrestin-1 is necessary for nicotine-mediated induction of mesenchymal genes
      vimentin and fibronectin as well as EMT regulators ZEB1 and ZEB2. Nicotine
      induced changes in cell morphology and ablate tight junctions consistent with
      EMT; beta-arrestin-1, but not beta-arrestin-2, was required for these changes.
      beta-Arrestin-1 promoted the expression of the mesenchymal genes, as well as ZEB1
      and ZEB2, through the mediation of the E2F1 transcription factor; this required
      Src kinase activity. Stimulation of multiple NSCLC cell lines with nicotine led
      to enhanced recruitment of beta-arrestin-1 and E2F1 on vimentin, fibronectin, and
      ZEB1 and ZEB2 promoters. Furthermore, there was significantly more beta-arrestin
      1 and E2F1 associated with these promoters in human NSCLC tumors, and beta
      arrestin-1 levels correlated with vimentin and fibronectin levels in human NSCLC
      samples. A549-luciferase cells lacking beta-arrestin-1 showed a significantly
      reduced capacity for tumor growth and metastasis when orthotopically implanted
      into the lungs of SCID-beige mice. Taken together, these studies reveal a novel
      role for beta-arrestin-1 in the growth and metastasis of NSCLC.

PMID- 25600649
TI  - Targeting LUNX inhibits non-small cell lung cancer growth and metastasis.
AB  - There remains a great need for effective therapies for lung cancer, the majority
      of which are non-small cell lung cancers (NSCLC). Here, we report the
      identification of a novel candidate therapeutic target, LUNX, as a molecule
      overexpressed in primary NSCLC and lymph node metastases that is associated with
      reduced postoperative survival. Functional studies demonstrated that LUNX
      overexpression promoted lung cancer cell migration and proliferation by
      interactions with the chaperone protein 14-3-3. Conversely, LUNX silencing
      disrupted primary tumor growth, local invasion, and metastatic colonization. The
      finding that LUNX was expressed on cell membranes prompted us to generate and
      characterize LUNX antibodies as a candidate therapeutic. Anti-LUNX could
      downregulate LUNX and reduce lung cancer cell proliferation and migration in
      vitro. Administered in vivo to mice bearing lung cancer xenografts, anti-LUNX
      could slow tumor growth and metastasis and improve mouse survival. Together, our
      work provides a preclinical proof of concept for LUNX as a novel candidate target
      for immunotherapy in lung cancer.

PMID- 25600650
TI  - Multichromophoric organic molecules encapsulated in polymer nanoparticles for
      artificial light harvesting.
AB  - We designed a self-assembled multichromophoric organic molecular arrangement
      inside polymer nanoparticles for light-harvesting antenna materials. The self
      assembled molecular arrangement of quaterthiophene molecules was found to be an
      efficient light-absorbing antenna material, followed by energy transfer to Nile
      red (NR) dye molecules, which was confined in polymer nanoparticles. The
      efficiency of the antenna effect was found to be 3.2 and the effective molar
      extinction coefficient of acceptor dye molecules was found to be enhanced, which
      indicates an efficient light-harvesting system. Based on this energy-transfer
      process, tunable photo emission and white light emission has been generated with
      14 % quantum yield. Such self-assembled oligothiophene-NR systems encapsulated in
      polymer nanoparticles may open up new possibilities for fabrication of artificial
      light harvesting system. 

PMID- 25600651
TI  - Synthesis and characterization of bicontinuous cubic poly(3,4-ethylene
      dioxythiophene) gyroid (PEDOT GYR) gels.
AB  - We describe the synthesis and characterization of bicontinuous cubic poly(3,4
      ethylenedioxythiophene) (PEDOT) conducting polymer gels prepared within lyotropic
      cubic poly(oxyethylene)10 nonylphenol ether (NP-10) templates with Ia3[combining
      macron]d (gyroid, GYR) symmetry. The chemical polymerization of EDOT monomer in
      the hydrophobic channels of the NP-10 GYR phase was initiated by AgNO3, a mild
      oxidant that is activated when exposed to ultraviolet (UV) radiation. The
      morphology and physical properties of the resulting PEDOT gels were examined as a
      function of temperature and frequency using optical and electron microscopy,
      small-angle X-ray scattering (SAXS), dynamic mechanical spectroscopy, and
      electrochemical impedance spectroscopy (EIS). Microscopy and SAXS results showed
      that the PEDOT gels remained ordered and stable after the UV-initiated chemical
      polymerization, confirming the successful templated-synthesis of PEDOT in
      bicontinuous GYR nanostructures. In comparison to unpolymerized 3,4
      ethylenedioxythiophene (EDOT) gel phases, the PEDOT structures had a higher
      storage modulus, presumably due to the formation of semi-rigid PEDOT-rich
      nanochannels. Additionally, the storage modulus (G') for PEDOT gels decreased
      only modestly with increasing temperature, from ~1.2 * 10(5) Pa (10  degrees C)
      to ~7 * 10(4) Pa (40  degrees C), whereas G' for the NP-10 and EDOT gels
      decreased dramatically, from ~5.0 * 10(4) Pa (10  degrees C) to ~1.5 * 10(2) Pa
      (40  degrees C). EIS revealed that the impedance of the PEDOT gels was smaller
      than the impedance of EDOT gels at both high frequencies (PEDOT ~10(2) Omega and
      EDOT 2-3 * 10(4) Omega at 10(5) Hz) and low frequencies (PEDOT 10(3)-10(5) Omega
      and EDOT ~5 * 10(5) Omega at 10(-1) Hz). These results indicated that PEDOT gels
      were highly ordered, mechanically stable and electrically conductive, and thus
      should be of interest for applications for which such properties are important,
      including low impedance and compliant coatings for biomedical electrodes. 

PMID- 25600653
TI  - Oxidative asymmetric umpolung alkylation of Evans' beta-ketoimides using
      dialkylzinc nucleophiles.
AB  - Umpolung alkylation of Evans' auxiliary substituted beta-ketoimides affords the
      diastereomerically pure products in yields ranging from 40 to 80%. The reaction
      itself proceeds with diastereoselectivities between 3 : 1 and 18 : 1. Dialkylzinc
      serves as the nucleophile and umpolung of the beta-keto-imide enolate is achieved
      by the action of Koser's reagent. 

PMID- 25600654
TI  - Sample size calculation in metabolic phenotyping studies.
AB  - The number of samples needed to identify significant effects is a key question in
      biomedical studies, with consequences on experimental designs, costs and
      potential discoveries. In metabolic phenotyping studies, sample size
      determination remains a complex step. This is due particularly to the multiple
      hypothesis-testing framework and the top-down hypothesis-free approach, with no a
      priori known metabolic target. Until now, there was no standard procedure
      available to address this purpose. In this review, we discuss sample size
      estimation procedures for metabolic phenotyping studies. We release an automated
      implementation of the Data-driven Sample size Determination (DSD) algorithm for
      MATLAB and GNU Octave. Original research concerning DSD was published elsewhere.
      DSD allows the determination of an optimized sample size in metabolic phenotyping
      studies. The procedure uses analytical data only from a small pilot cohort to
      generate an expanded data set. The statistical recoupling of variables procedure
      is used to identify metabolic variables, and their intensity distributions are
      estimated by Kernel smoothing or log-normal density fitting. Statistically
      significant metabolic variations are evaluated using the Benjamini-Yekutieli
      correction and processed for data sets of various sizes. Optimal sample size
      determination is achieved in a context of biomarker discovery (at least one
      statistically significant variation) or metabolic exploration (a maximum of
      statistically significant variations). DSD toolbox is encoded in MATLAB R2008A
      (Mathworks, Natick, MA) for Kernel and log-normal estimates, and in GNU Octave
      for log-normal estimates (Kernel density estimates are not robust enough in GNU
      octave). It is available at http://www.prabi.fr/redmine/projects/dsd/repository,
      with a tutorial at http://www.prabi.fr/redmine/projects/dsd/wiki. 

PMID- 25600652
TI  - The impact of socioeconomic status on foodborne illness in high-income countries:
      a systematic review.
AB  - Foodborne illness is a major cause of morbidity and loss of productivity in
      developed nations. Although low socioeconomic status (SES) is generally
      associated with negative health outcomes, its impact on foodborne illness is
      poorly understood. We conducted a systematic review to examine the association
      between SES and laboratory-confirmed illness caused by eight important foodborne
      pathogens. We completed this systematic review using PubMed for all papers
      published between 1 January 1980 and 1 January 2013 that measured the association
      between foodborne illness and SES in highly developed countries and identified 16
      studies covering four pathogens. The effect of SES varied across pathogens: the
      majority of identified studies for Campylobacter, salmonellosis, and E. coli
      infection showed an association between high SES and illness. The single study of
      listeriosis showed illness was associated with low SES. A reporting bias by SES
      could not be excluded. SES should be considered when targeting consumer-level
      public health interventions for foodborne pathogens. 

PMID- 25600656
TI  - Severe atopic dermatitis associated with transient hypogammaglobulinemia of
      infancy.

PMID- 25600655
TI  - Improving Aboriginal women's experiences of antenatal care: findings from the
      Aboriginal families study in South Australia.
AB  - BACKGROUND: Aboriginal and Torres Strait Islander families experience markedly
      worse maternal and child health outcomes than non-Aboriginal families. The
      objective of this study was to investigate the experiences of women attending
      Aboriginal Family Birthing Program services in South Australia compared with
      women attending mainstream public antenatal care. METHOD: Population-based survey
      of mothers of Aboriginal babies giving birth in urban, regional, and remote areas
      of South Australia between July 2011 and June 2013. RESULTS: A total of 344 women
      took part in the study around 4-9 months after giving birth; 93 percent were
      Aboriginal and/or Torres Strait Islanders, and 7 percent were non-Aboriginal
      mothers of Aboriginal babies. Of these, 39 percent of women lived in a major
      city, 36 percent in inner or outer regional areas, and 25 percent in remote areas
      of South Australia. Compared with women attending mainstream public antenatal
      care, women attending metropolitan and regional Aboriginal Family Birthing
      Program services had a higher likelihood of reporting positive experiences of
      pregnancy care (adjOR 3.4 [95% CI 1.6-7.0] and adjOR 2.4 [95% CI 1.4-4.3],
      respectively). Women attending Aboriginal Health Services were also more likely
      to report positive experiences of care (adjOR 3.5 [95% CI 1.3-9.4]). CONCLUSIONS:
      In the urban, regional, and remote areas where the Aboriginal Family Birthing
      Program has been implemented, the program has expanded access to culturally
      responsive antenatal care for Aboriginal women and families. The positive
      experiences reported by many women using the program have the potential to
      translate into improved outcomes for Aboriginal families.

PMID- 25600657
TI  - Folic acid: building bigger babies.

PMID- 25600658
TI  - Shear bond strength of an orthodontic self-etching adhesive after intracoronary
      bleaching.
AB  - OBJECTIVES: To evaluate the effects of intracoronary bleaching on the bond
      strength of orthodontic brackets using self-etching and total-etch adhesive
      systems. MATERIAL AND METHODS: In 60 bovine incisors, a coronal lingual access
      was made to clean the pulp chamber and standardise the thickness of the dentine.
      The sample was randomly divided into four groups (each n = 15): (CT), control
      group, without bleaching and bonded with the total-etch system (Transbond(TM) XT
      3M); (CTSE), without bleaching treatment and bonded with the self-etching system
      (Transbond(TM) Plus Self-Etching Primer-3M); (BT), treated with 35% hydrogen
      peroxide for internal bleaching and bonded with the total-etch adhesive system;
      and (BTSE), treated with 35% hydrogen peroxide and bonded with the self-etching
      adhesive system. Shear bond strength was measured using a universal testing
      machine (EMIC). The adhesive remnant index (ARI) score was verified. The data
      were analysed using a two-way anova and Tukey test (p < 0.05). RESULTS:
      Significant differences were found, and the self-etching adhesive groups
      presented the highest bond strength values (CTSE=11.55 +/- 2.85 MPa; BTSE=14.14
      +/- 2.23 MPa). The ARI scores revealed significant differences among the groups;
      the greater amount of remaining adhesive was observed in the CTSE group, and the
      lowest scores were observed in the BT group. CONCLUSIONS: The use of the self
      etching adhesive system, even after intracoronal bleaching, presented
      satisfactory adhesive strength for the bonding of brackets.

PMID- 25600659
TI  - Quantitative comparison of low dose and standard dose radioiodine therapy
      effectiveness in patients with low risk differentiated thyroid cancer.
AB  - BACKGROUND: The aim of this paper was to compare the results of postoperative I
      131 remnant ablation therapy using a quantitative data in the low activity (1110
      MBq) and standard dose (3700 MBq). METHODS: The study included two groups of
      patients with low risk differentiated thyroid cancer (DTC): Group L (low dose
      group) included 54 patients who were treated with 1110 MBq I-131 and Group S
      (standard dose group) included 61 patients treated with 3700 MBq. The
      postoperative thyroid remnants were assessed with the pretreatment thyroid uptake
      test (PTUT) and the whole body scans (WBS) were performed in the 7th day after
      the ablation treatment. We obtained the average count per pixel from the standard
      region of interest analysis of the thyroid bed (Tavc), liver (Lavc), thigh
      (Thavc) and whole body (WBkc). At the sixth month after the treatment, WBS were
      performed to 106 patients (45 patients from Group L and 61 patients from Group S)
      to evaluate the success of ablation treatment. RESULTS: A significant difference
      in PTUT and Tavc was not found between the two groups (P>0.05). However, Lavc,
      Thavc and WBkc were significantly higher in Group S compared with Group L
      (P<0.001). Although the percentage of ablation was higher in Group S (49 of 61
      patients, 80.3% versus 34 of 45 patients, 75.6%), the statistical difference was
      not significant (P>0.05). CONCLUSIONS: In low risk DTC patients, low dose
      radioactive iodine can ablate thyroid remnants as effectively as a higher dose
      with less radiation exposure to other non-target organs and the whole body.

PMID- 25600660
TI  - Electrogenic and nonelectrogenic ion fluxes across lipid and mitochondrial
      membranes mediated by monensin and monensin ethyl ester.
AB  - Monensin is a carrier of cations through lipid membranes capable of exchanging
      sodium (potassium) cations for protons by an electroneutral mechanism, whereas
      its ethyl ester derivative ethyl-monensin is supposed to transport sodium
      (potassium) cations in an electrogenic manner. To elucidate mechanistic details
      of the ionophoric activity, ion fluxes mediated by monensin and ethyl-monensin
      were measured on planar bilayer lipid membranes, liposomes, and mitochondria. In
      particular, generation of membrane potential on liposomes was studied via the
      measurements of rhodamine 6G uptake by fluorescence correlation spectroscopy. In
      mitochondria, swelling experiments were expounded by the additional measurements
      of respiration, membrane potential, and matrix pH. It can be concluded that both
      monensin and ethyl-monensin can perform nonelectrogenic exchange of potassium
      (sodium) ions for protons and serve as electrogenic potassium ion carriers
      similar to valinomycin. The results obtained are in line with the predictions
      based on the crystal structures of the monensin complexes with sodium ions and
      protons (Huczynski et al., Biochim. Biophys. Acta, 1818 (2012) pp. 2108-2119).
      The functional activity observed for artificial membranes and mitochondria can be
      applied to explain the activity of ionophores in living systems. It can also be
      important for studying the antitumor activity of monensin. 

PMID- 25600661
TI  - Exploring the potentials of nurture: 2(nd) and 3(rd) generation explant human
      skin equivalents.
AB  - BACKGROUND: Explant human skin equivalents (Ex-HSEs) can be generated by placing
      a 4mm skin biopsy onto a dermal equivalent. The keratinocytes migrate from the
      biopsy onto the dermal equivalent, differentiate and form the epidermis of 1(st)
      generation Ex-HSEs. This is especially suitable for the expansion of skin
      material from which only small fragments of skin can be harvested e.g. diseased
      skin. OBJECTIVE: We evaluated whether 2(nd) and 3(rd) generation Ex-HSEs can also
      be generated from a single skin biopsy whilst maintaining the epidermal
      properties of 1(st) generation Ex-HSEs and native human skin. METHODS: 2(nd)
      generation Ex-HSEs were produced by placing a biopsy from the 1(st) generation Ex
      HSE onto a new dermal equivalent. Likewise, the 3(rd) generation Ex-HSEs were
      generated from a 2(nd) generation Ex-HSE biopsy. RESULTS: We show for the first
      time that Ex-HSEs can be passaged to the 2(nd) and 3(rd) generation and display
      similar epidermal morphology and expression of differentiation markers as in
      native human skin and 1(st) generation Ex-HSEs except for involucrin. The 2(nd)
      and 3(rd) generation Ex-HSEs also show many similarities with 1(st) generation Ex
      HSEs in lipid properties e.g. presence of all lipid classes, similar fatty acid
      chain length distribution and lamellar lipid organization. However, some
      differences arise in increased level of hexagonal lateral packing and a change in
      ceramide profiling. The changes in specific lipid classes were also accompanied
      by changes in the expression of the enzymes responsible for their synthesis.
      CONCLUSION: The expansion of skin biopsies to the 2(nd) and 3(rd) generation Ex
      HSEs could be a promising method to expand valuable epidermal tissue to analyze
      morphological and differentiation parameters in the native epidermis.

PMID- 25600662
TI  - N-linked glycosylation on laminin gamma1 influences recognition of anti-laminin
      gamma1 pemphigoid autoantibodies.

PMID- 25600663
TI  - Targeting the 5'-AMP-activated protein kinase and related metabolic pathways for
      the treatment of prostate cancer.
AB  - INTRODUCTION: Increasing evidence suggests that prostate cancer cells undergo
      unique metabolic reprogramming during transformation. A master regulator of
      cellular homeostasis, 5'-AMP-activated protein kinase (AMPK), directs metabolic
      adaptation that supports the growth demands of rapidly dividing cancer cells. The
      utilization of AMPK as a therapeutic target may therefore provide an effective
      strategy in the treatment of prostate cancer. AREAS COVERED: Our review describes
      the regulation of AMPK by androgens and upstream kinases including the
      calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in prostate cancer.
      Oncogenic, AMPK-regulated pathways that direct various metabolic processes are
      also addressed. Furthermore, we discuss the role of AMPK in growth arrest and
      autophagy as a potential survival pathway for cancer cells. In addition, by
      regulating non-metabolic pathways, AMPK may stimulate migration and mitosis.
      Finally, this review summarizes efforts to treat prostate cancer with
      pharmacological agents capable of modulating AMPK signaling. EXPERT OPINION:
      Current research is primarily focused on developing drugs that activate AMPK as a
      treatment for prostate cancer. However, oncogenic aspects of AMPK signaling calls
      for caution about employing such therapies. We think that inhibitors of CaMKK2 or
      AMPK, or perhaps the modulation of downstream targets of AMPK, will gain
      importance in the clinical management of prostate cancer.

PMID- 25600664
TI  - Dynamic clinical data mining: search engine-based decision support.
AB  - The research world is undergoing a transformation into one in which data, on
      massive levels, is freely shared. In the clinical world, the capture of data on a
      consistent basis has only recently begun. We propose an operational vision for a
      digitally based care system that incorporates data-based clinical decision
      making. The system would aggregate individual patient electronic medical data in
      the course of care; query a universal, de-identified clinical database using
      modified search engine technology in real time; identify prior cases of
      sufficient similarity as to be instructive to the case at hand; and populate the
      individual patient's electronic medical record with pertinent decision support
      material such as suggested interventions and prognosis, based on prior outcomes.
      Every individual's course, including subsequent outcomes, would then further
      populate the population database to create a feedback loop to benefit the care of
      future patients. 

PMID- 25600665
TI  - Dynamical phases in quenched spin-orbit-coupled degenerate Fermi gas.
AB  - The spin-orbit-coupled degenerate Fermi gas provides a new platform for realizing
      topological superfluids and related topological excitations. However, previous
      studies have been mainly focused on the topological properties of the stationary
      ground state. Here, we investigate the quench dynamics of a spin-orbit-coupled
      two-dimensional Fermi gas in which the Zeeman field serves as the major quench
      parameter. Three post-quench dynamical phases are identified according to the
      asymptotic behaviour of the order parameter. In the undamped phase, a persistent
      oscillation of the order parameter may support a topological Floquet state with
      multiple edge states. In the damped phase, the magnitude of the order parameter
      approaches a constant via a power-law decay, which may support a dynamical
      topological phase with one edge state at the boundary. In the overdamped phase,
      the order parameter decays to zero exponentially although the condensate fraction
      remains finite. These predictions can be observed in the strong-coupling regime. 

PMID- 25600666
TI  - Implementation of the global risk analysis in pulsed-dose rate brachytherapy:
      methods and results.
AB  - PURPOSE: To report the application of the global risk analysis (GRA) in the
      pulsed-dose rate (PDR) brachytherapy workflow. MATERIAL AND METHODS: Analyses
      were led by a multidisciplinary working group established within the unit with
      the guidance of a quality engineer. First, a mapping of hazardous situations was
      developed as a result of interactions between the patient workflow for a
      treatment using PDR brachytherapy split into 51 sub-phases with a comprehensive
      list of the hazards that he/she faces (44). Interactions, when relevant, were
      sorted by level of priority: to be treated immediately, secondarily (the group is
      not entitled to treat the situation), or later (safe situation). Secondly, for
      each high priority dangerous situation, scenarios were developed to anticipate
      their potential consequences. Criticality was assessed, using likelihood and
      severity scales and a matrix, which allocated risks into categories: acceptable
      (C1), tolerable under control (C2) and unacceptable (C3). Then, corrective
      actions were proposed and planned when relevant, after assessment of their
      feasibility with a scale of effort. Finally, the criticality of the scenarios was
      reevaluated, taking into account the implementation of these actions, leading to
      a residual risk mapping, which could trigger additional proposals of actions.
      RESULTS: Two thousand one hundred and eighty-four potential interactions between
      the list of hazards and the workflow were analyzed. Mapping of dangerous
      situations identified 213 relevant interactions, from which 61 were considered
      with high priority. One hundred and twenty-six scenarios were generated: 68 with
      a low criticality (74.3%), 58 with an intermediate score (25.7%). No scenario
      with the highest criticality was individualized. Twenty-one corrective actions
      were planned. Mapping of residual risk resulted in the disappearance of most C2
      risks, leaving 5 C2 scenarios (4%), for which four monitoring indicators were
      implemented in addition to the corrected actions decided on. CONCLUSION: The
      implementation of the GRA appeared feasible, and led to implement 21 corrective
      actions, based on scenarios and not on incidents.

PMID- 25600667
TI  - The impact of the media on the decision of parents in South Wales to accept
      measles-mumps-rubella (MMR) immunization.
AB  - A large measles outbreak occurred in South Wales in 2012/2013. The outbreak has
      been attributed to low take-up of measles-mumps-rubella (MMR) immunization in the
      early 2000s. To understand better the factors that led to this outbreak we
      present the findings of a case-control study carried out in the outbreak area in
      2001 to investigate parents' decision on whether to accept MMR. Parents who
      decided not to take-up MMR at the time were more likely to be older and better
      educated, more likely to report being influenced by newspapers [adjusted odds
      ratio (aOR) 3.07, 95% confidence interval (CI) 1.62-5.80], television (aOR 3.30,
      95% CI 1.70-6.43), the internet (aOR 7.23, 3.26-16.06) and vaccine pressure
      groups (aOR 5.20, 95% CI 2.22-12.16), and less likely to be influenced by a
      health visitor (aOR 0.30, 95% CI 0.16-0.57). In this area of Wales, daily English
      language regional newspapers, UK news programmes and the internet appeared to
      have a powerful negative influence. We consider the relevance of these findings
      to the epidemiology of the outbreak and the subsequent public health response.

PMID- 25600669
TI  - Comparison of smear layer removal using the Nd:YAG laser, ultrasound, ProTaper
      Universal system, and CanalBrush methods: an in vitro study.
AB  - INTRODUCTION: The aim of this study was to compare the efficacy of the Nd:YAG
      laser, ultrasound, the ProTaper Universal system (Dentsply Maillefer, Ballaigues,
      Switzerland), and the CanalBrush (Coltene Whaledent, Langenau, Germany) methods
      for the removal of the smear layer from the apical third of root canals. METHODS:
      Fifty distal root canals from extracted human mandibular first molars were
      instrumented up to ProTaper Universal F5 and divided randomly into 5 groups (n =
      10) according to the following final irrigation agitation techniques: no
      agitation (control), ProTaper Universal file, ultrasound, CanalBrush, and Nd:YAG
      laser. Specimens were observed under a scanning electron microscope. The presence
      of the smear layer was evaluated using a 3-grade scoring system. The data were
      analyzed with Cohen kappa, Kruskal-Wallis, and Mann-Whitney U tests. A level of
      significance of .05 was adopted. RESULTS: The ultrasound group performed
      significantly better than the rest of the groups; 56.6% of the specimens revealed
      no smear layer, 44.4% showed the presence of a moderate smear layer, and no heavy
      smear layers were observed. In the Nd:YAG laser group, 30% of the specimens
      presented with no smear layer, 70% showed the presence of a moderate smear layer,
      and no heavy smear layers were observed. In contrast, a heavy smear layer was
      observed on the surfaces of the root canals in the CanalBrush (23.4%), ProTaper
      Universal (13.4%), and control (86.6%) groups. Statistically significant
      differences were observed (P < .05). CONCLUSIONS: None of the agitation methods
      completely removed the smear layer. However, the ultrasound method performed
      significantly better followed by the Nd:YAG laser, the CanalBrush, and the
      ProTaper Universal system. Agitation of the irrigant improved smear layer removal
      in the apical third of the canal.

PMID- 25600668
TI  - Seroepidemiology of Toxoplasma in a coastal region of Haiti: multiplex bead assay
      detection of immunoglobulin G antibodies that recognize the SAG2A antigen.
AB  - Toxoplasma gondii is a globally distributed parasitic protozoan that infects most
      warm-blooded animals. We incorporated a bead coupled with recombinant SAG2A
      protein into our Neglected Tropical Disease (NTD) multiplex bead assay (MBA)
      panel and used it to determine Toxoplasma infection rates in two studies in
      Haiti. In a longitudinal cohort study of children aged 0-11 years, the infection
      rate varied with age reaching a maximum of 0.131 infections/year in children aged
      3 years [95% confidence interval (CI) 0.065-0.204]. The median time to
      seroconversion was estimated to be 9.7 years (95% CI 7.6-infinity). In a cross
      sectional, community-wide survey of residents of all ages, we determined an
      overall seroprevalence of 28.2%. The seroprevalence age curve from the cross
      sectional study also suggested that the force of infection varied with age and
      peaked at 0.057 infections/year (95% CI 0.033-0.080) at age 2.6 years.
      Integration of the Toxoplasma MBA into NTD surveys may allow for better estimates
      of the potential burden of congenital toxoplasmosis in underserved regions.

PMID- 25600670
TI  - The state of radiologic teaching practice in preclinical medical education:
      survey of American medical, osteopathic, and podiatric schools.
AB  - PURPOSE: This study describes the state of preclinical radiology curricula in
      North American allopathic, osteopathic, and podiatric medical schools. METHODS:
      An online survey of teaching methods, radiology topics, and future plans was
      developed. The Associations of American Medical Colleges, Colleges of Osteopathic
      Medicine, and Colleges of Podiatric Medicine listing for all US, Canadian, and
      Puerto Rican schools was used for contact information for directors of anatomy
      and/or radiology courses. Letters were sent via e-mail to 198 schools, with a
      link to the anonymous survey. RESULTS: Of 198 schools, 98 completed the survey
      (48%). Radiology curricula were integrated with other topics (91%), and taught by
      anatomists (42%) and radiologists (43%). The majority of time was spent on the
      topic of anatomy correlation (35%). Time spent teaching general radiology topics
      in the curriculum, such as physics (3%), modality differences (6%), radiation
      safety (2%), and contrast use (2%) was limited. Most schools had plans to
      implement an innovative teaching method in the near future (62%). The major
      challenges included limits on: time in the curriculum (73%); resources (32%); and
      radiology faculty participation (30%). A total of 82% reported that their
      curriculum did not model the suggestions made by the Alliance of Medical Student
      Educators in Radiology. CONCLUSIONS: This survey describes the current state of
      preclinical radiology teaching: curricula were nonstandard, integrated into other
      courses, and predominantly used for anatomy correlation. Other important
      contextual principles of the practice of radiology were seldom taught.

PMID- 25600671
TI  - RF rectifiers for EM power harvesting in a Deep Brain Stimulating device.
AB  - A passive deep brain stimulation (DBS) device can be equipped with a rectenna,
      consisting of an antenna and a rectifier, to harvest energy from electromagnetic
      fields for its operation. This paper presents optimization of radio frequency
      rectifier circuits for wireless energy harvesting in a passive head-mountable DBS
      device. The aim is to achieve a compact size, high conversion efficiency, and
      high output voltage rectifier. Four different rectifiers based on the Delon
      doubler, Greinacher voltage tripler, Delon voltage quadrupler, and 2-stage charge
      pumped architectures are designed, simulated, fabricated, and evaluated. The
      design and simulation are conducted using Agilent Genesys at operating frequency
      of 915 MHz. A dielectric substrate of FR-4 with thickness of 1.6 mm, and surface
      mount devices (SMD) components are used to fabricate the designed rectifiers. The
      performance of the fabricated rectifiers is evaluated using a 915 MHz radio
      frequency (RF) energy source. The maximum measured conversion efficiency of the
      Delon doubler, Greinacher tripler, Delon quadrupler, and 2-stage charge pumped
      rectifiers are 78, 75, 73, and 76 % at -5 dBm input power and for load
      resistances of 5-15 kOmega. The conversion efficiency of the rectifiers decreases
      significantly with the increase in the input power level. The Delon doubler
      rectifier provides the highest efficiency at both -5 and 5 dBm input power
      levels, whereas the Delon quadrupler rectifier gives the lowest efficiency for
      the same inputs. By considering both efficiency and DC output voltage, the charge
      pump rectifier outperforms the other three rectifiers. Accordingly, the optimised
      2-stage charge pumped rectifier is used together with an antenna to harvest
      energy in our DBS device.

PMID- 25600672
TI  - Hippocampal dendritic spines remodeling and fear memory are modulated by
      GABAergic signaling within the basolateral amygdala complex.
AB  - GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial
      role on the modulation of the stress influence on fear memory. Moreover,
      accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream
      target of BLA neurons in contextual fear. Given that hippocampal structural
      plasticity is proposed to provide a substrate for the storage of long-term
      memories, the main aim of this study is to evaluate the modulation of GABA
      neurotransmission in the BLA on spine density in the DH following stress on
      contextual fear learning. The present findings show that prior stressful
      experience promoted contextual fear memory and enhanced spine density in the DH.
      Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented
      the facilitating influence of stress on both fear retention and hippocampal
      dendritic spine remodeling. Similarly to the stress-induced effects, the blockade
      of GABAa sites within the BLA ameliorated fear memory emergence and induced
      structural remodeling in the DH. These findings suggest that GABAergic
      transmission in BLA modulates the structural changes in DH associated to the
      influence of stress on fear memory.

PMID- 25600673
TI  - Early preterm sepsis: too complex to solve.

PMID- 25600674
TI  - Reply to Kartal & Kartal. Early preterm sepsis: too complex to solve.

PMID- 25600675
TI  - Factors associated with six-year weight change in young and middle-aged adults in
      the Young Finns Study.
AB  - OBJECTIVE: To examine factors associated with weight change and obesity risk in
      young and middle-aged adults. SUBJECTS/METHODS: The Young Finns Study with its
      923 women and 792 men aged 24-39 years at baseline were followed for six years.
      Variables associated with the weight change were investigated with regression
      models. RESULTS: The average weight change was 0.45 kg/year in women and 0.58
      kg/year in men. In women, weight change was steady across all ages. In men,
      weight changes were more pronounced in younger age groups. In women (weight gain
      > 2 kg, n = 490), medication for anxiety, low occupational status, high baseline
      BMI (body mass index), high intake of sweet beverages, high childhood BMI, high
      salt (NaCl and/or KCl) use, low number of children, low childhood family income,
      high stature and low level of dependence (a temperament subscale) were associated
      with increased weight gain (in the order of importance). In men (weight gain > 2
      kg, n = 455), high stature, high intake of french fries, low intake of sweet
      cookies, young age, recent divorce, low intake of cereals, high intake of milk,
      depressive symptoms, rural childhood origin, high baseline BMI and unemployment
      were associated with more pronounced weight gain. Sedentarity (screen-time) was
      associated with weight gain only in young men. Physical activity and genetic risk
      for high BMI (score of 31 known variants) were not consistently associated with
      weight change. CONCLUSIONS: Socio-economic factors, temperamental and physical
      characteristics, and some dietary factors are related with weight change in
      young/middle-aged adults. The weight change occurring in adulthood is also
      determined by childhood factors, such as high BMI and low family income.

PMID- 25600677
TI  - Macular lymphocytic arteritis, a new cutaneous vasculitis.

PMID- 25600676
TI  - An open-label phase I/II study of cyclophosphamide, bortezomib, pegylated
      liposomal doxorubicin, and dexamethasone in newly diagnosed myeloma.
AB  - We conducted a phase 1/2 trial evaluating the combination of cyclophosphamide,
      bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly
      diagnosed multiple myeloma (MM). The primary objective of the phase 1 was to
      evaluate the safety and tolerability of maximum planned dose (MPD) and the phase
      2 was to assess the overall response rate. Patients received 6-8 cycles of CVDD
      at four dose levels. There were no dose-limiting toxicities. The MPD was
      cyclophosphamide 750 mg/m(2) IV on day 1, bortezomib 1.3 mg/m(2) IV on days 1, 4,
      8, 11, pegylated liposomal doxorubicin 30 mg/m(2) IV on day 4, and dexamethasone
      20 mg orally on the day of and after bortezomib (21-d cycle). Forty-nine patients
      were treated at the MPD of which 22% had high-risk myeloma. The most common grade
      >=3 toxicities included myelosuppression, infection, and fatigue. Overall
      response and complete response rates were 91% and 26% in standard-risk, and 100%
      and 58% in high-risk cohort, respectively. After a median follow-up of 34 months,
      the median progression-free survival was 31.3 months. The 2-yr overall survival
      was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively.
      CVDD regimen was well tolerated and was highly active in newly diagnosed MM.

PMID- 25600679
TI  - Incremental value of myocardial perfusion over coronary angiography by spectral
      computed tomography in patients with intermediate to high likelihood of coronary
      artery disease.
AB  - PURPOSE: We sought to explore the diagnostic performance of dual energy computed
      tomography (DECT) for the evaluation of myocardial perfusion in patients with
      intermediate to high likelihood of coronary artery disease (CAD). MATERIALS AND
      METHODS: Consecutive patients with known or suspected CAD referred for myocardial
      perfusion imaging by single-photon emission computed tomography (SPECT)
      constituted the study population and were scanned using a DECT scanner equipped
      with gemstone detectors for spectral imaging, and a SPECT. The same
      pharmacological stress was used for both scans. RESULTS: Twenty-five patients
      were prospectively included in the study protocol. The mean age was 63.4+/-10.6
      years. The total mean effective radiation dose was 7.5+/-1.2 mSv with DECT and
      8.2+/-1.7 mSv with SPECT (p=0.007). A total of 425 left ventricular segments were
      evaluated by DECT, showing a reliable accuracy for the detection of reversible
      perfusion defects [area under ROC curve (AUC) 0.84 (0.80-0.87)]. Furthermore,
      adding stress myocardial perfusion provided a significant incremental value over
      anatomical evaluation alone by computed tomography coronary angiography [AUC 0.70
      (0.65-0.74), p=0.003]. CONCLUSIONS: In this pilot investigation, stress
      myocardial perfusion by DECT demonstrated a significant incremental value over
      anatomical evaluation alone by CTCA for the detection of reversible perfusion
      defects.

PMID- 25600678
TI  - Post-mortem computed tomography findings of the lungs: Retrospective review and
      comparison with autopsy results of 30 infant cases.
AB  - OBJECTIVES: Infant cases frequently show a diffuse increase in the concentration
      of lung fields on post-mortem computed tomography (PMCT). However, the lungs
      often show simply atelectasis at autopsy in the absence of any other abnormal
      changes. Thus, we retrospectively reviewed the PMCT findings of lungs following
      sudden infant death and correlated them with the autopsy results. MATERIALS AND
      METHODS: We retrospectively reviewed infant cases (0 year) who had undergone PMCT
      and a forensic autopsy at our institution between May 2009 and June 2013. Lung
      opacities were classified according to their type; consolidation, ground-glass
      opacity and mixed, as well as distribution; bilateral diffuse and areas of
      sparing. Statistical analysis was performed to assess the relationships among
      lung opacities, causes of death and resuscitation attempt. RESULTS: Thirty infant
      cases were selected, which included 22 sudden and unexplained deaths and 8 other
      causes of death. Resuscitation was attempted in 22 of 30 cases. Bilateral diffuse
      opacities were observed in 21 of the 30 cases. Of the 21 cases, 18 were sudden
      and unexplained deaths. Areas of sparing were observed in 4 sudden and
      unexplained deaths and 5 other causes of death. Distribution of opacities was not
      significantly associated with causes of death or resuscitation attempt. The 21
      cases with bilateral diffuse opacities included 6 consolidations (4 sudden and
      unexplained deaths, 2 other causes of death), 4 ground-glass opacities (3 sudden
      and unexplained deaths and 1 other) and 11 mixed (11 sudden and unexplained
      deaths). Types of opacities were not significantly associated with causes of
      death or resuscitation attempt. CONCLUSION: Atelectasis is very common in sudden
      and unexplained death of infants. Bilateral diffuse mixed opacity was observed
      only in sudden and unexplained deaths. Bilateral diffuse pure consolidation or
      ground-glass opacity was also observed in other causes of death.

PMID- 25600681
TI  - Electronic structure, vibrational spectral and intervening orbital interactions
      studies of NLO material: guanidinium 4-nitrobenzoate.
AB  - Single crystals of guanidinium 4-nitrobenzoate (GPNB) have been grown by slow
      evaporation method. Grown crystals were characterized by FT-IR, FT-Raman, UV-Vis
      absorption and UV-Vis transmission spectroscopies. Crystal defects and surface
      morphology were studied by etching method. Dielectric properties of the crystal
      such as dielectric constant, dielectric loss and AC electrical conductivity as
      function of frequency (50 Hz-5 MHz) at two temperatures (35 degrees C and 100
      degrees C) were measured. The frequency and temperature dependence of dielectric
      behaviour were investigated. The equilibrium geometry, vibrational spectral
      analysis, intramolecular charge transfer interactions using NBO method, first
      order hyperpolarizability, molecular electrostatic potential and frontier
      molecular orbital analysis for GPNB have been studied using density functional
      theory at B3LYP/cc-pVTZ level. Vibrational spectral study reveals the presence of
      moderate and weak N-H?O bonds in GPNB. NBO analysis also confirms the presence of
      intramolecular N-H?O hydrogen bonding and investigates the stability as well as
      the intervening orbital interactions. The electronic absorption spectrum of the
      gas and water phases of GPNB were simulated using time dependent density
      functional theory and NBO transitions for the three lowest excited states were
      assigned and studied.

PMID- 25600683
TI  - Using carbon dioxide as a building block in organic synthesis.
AB  - Carbon dioxide exits in the atmosphere and is produced by the combustion of
      fossil fuels, the fermentation of sugars and the respiration of all living
      organisms. An active goal in organic synthesis is to take this carbon--trapped in
      a waste product--and re-use it to build useful chemicals. Recent advances in
      organometallic chemistry and catalysis provide effective means for the chemical
      transformation of CO2 and its incorporation into synthetic organic molecules
      under mild conditions. Such a use of carbon dioxide as a renewable one-carbon
      (C1) building block in organic synthesis could contribute to a more sustainable
      use of resources.

PMID- 25600682
TI  - Effectiveness of shrinkage and variable selection methods for the prediction of
      complex human traits using data from distantly related individuals.
AB  - Genome-wide association studies (GWAS) have detected large numbers of variants
      associated with complex human traits and diseases. However, the proportion of
      variance explained by GWAS-significant single nucleotide polymorphisms has been
      usually small. This brought interest in the use of whole-genome regression (WGR)
      methods. However, there has been limited research on the factors that affect
      prediction accuracy (PA) of WGRs when applied to human data of distantly related
      individuals. Here, we examine, using real human genotypes and simulated
      phenotypes, how trait complexity, marker-quantitative trait loci (QTL) linkage
      disequilibrium (LD), and the model used affect the performance of WGRs. Our
      results indicated that the estimated rate of missing heritability is dependent on
      the extent of marker-QTL LD. However, this parameter was not greatly affected by
      trait complexity. Regarding PA our results indicated that: (a) under perfect
      marker-QTL LD WGR can achieve moderately high prediction accuracy, and with
      simple genetic architectures variable selection methods outperform shrinkage
      procedures and (b) under imperfect marker-QTL LD, variable selection methods can
      achieved reasonably good PA with simple or moderately complex genetic
      architectures; however, the PA of these methods deteriorated as trait complexity
      increases and with highly complex traits variable selection and shrinkage methods
      both performed poorly. This was confirmed with an analysis of human height. 

PMID- 25600684
TI  - Low Frequency of Peripheral Lymphocyte in Chronic Hepatitis B Patients Predicts
      Poor Progression to Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and
      the second leading cause of cancer-related deaths worldwide. The poor prognosis
      of HCC is mainly because of its discovery at advanced stages. Because chronic
      hepatitis B (CHB) accounts for 50-80% HCC occurrence worldwide, and immunity is
      regarded as an emerging hallmark of cancer, we investigated the predictive role
      of peripheral immune cells in HCC incidence in CHB patients. METHODS: This
      investigation collected and analyzed data from 89 CHB patients, 94 primary HCC
      patients with hepatitis B virus (HBV), 81 primary HCC patients without HBV, 69
      normal healthy patients, and 257 CHB patients with at least 3-year regular
      followup. RESULTS: The results demonstrated that CHB and primary HCC patients had
      different concentrations of lymphocytes, neutrophils, and monocytes in their
      peripheral circulation. Further study showed that the peripheral lymphocyte
      concentration was an independent prognostic factor for HCC incidence in CHB
      patients during the 3 years of followup. Finally, a predictive HCC incidence
      model with an AUROC (area under the receiver operating characteristic) of 0.832
      was constructed based on the peripheral lymphocyte concentration, serum alpha
      fetoprotein (AFP) concentration, and cirrhosis status of CHB patients.
      CONCLUSIONS: The peripheral lymphocyte concentration was an independent
      prognostic factor for HCC incidence in CHB patients, and a more accurate
      predictive model based on peripheral lymphocytes, serum AFP, and cirrhosis status
      was constructed.

PMID- 25600686
TI  - Real-time analysis of organic compounds in ship engine aerosol emissions using
      resonance-enhanced multiphoton ionisation and proton transfer mass spectrometry.
AB  - Organic combustion aerosols from a marine medium-speed diesel engine, capable to
      run on distillate (diesel fuel) and residual fuels (heavy fuel oil), were
      investigated under various operating conditions and engine parameters. The online
      chemical characterisation of the organic components was conducted using a
      resonance-enhanced multiphoton ionisation time-of-flight mass spectrometer (REMPI
      TOF MS) and a proton transfer reaction-quadrupole mass spectrometer (PTR-QMS).
      Oxygenated species, alkenes and aromatic hydrocarbons were characterised.
      Especially the aromatic hydrocarbons and their alkylated derivatives were very
      prominent in the exhaust of both fuels. Emission factors of known health
      hazardous compounds (e.g. mono- and poly-aromatic hydrocarbons) were calculated
      and found in higher amounts for heavy fuel oil (HFO) at typical engine loadings.
      Lower engine loads lead in general to increasing emissions for both fuels for
      almost every compound, e.g. naphthalene emissions varied for diesel fuel exhaust
      between 0.7 mg/kWh (75 % engine load, late start of injection (SOI)) and 11.8
      mg/kWh (10 % engine load, late SOI) and for HFO exhaust between 3.3 and 60.5
      mg/kWh, respectively. Both used mass spectrometric techniques showed that they
      are particularly suitable methods for online monitoring of combustion compounds
      and very helpful for the characterisation of health-relevant substances.
      Graphical abstract Three-dimensional REMPI data of organic species in diesel fuel
      and heavy fuel oil exhaust. 

PMID- 25600685
TI  - DNA copy number concentration measured by digital and droplet digital
      quantitative PCR using certified reference materials.
AB  - The value assignment for properties of six certified reference materials (ERM
      AD623a-f), each containing a plasmid DNA solution ranging from 1 million to 10
      copies per MUL, by using digital PCR (dPCR) with the BioMarkTM HD System
      (Fluidigm) has been verified by applying droplet digital PCR (ddPCR) using the
      QX100 system (Bio-Rad). One of the critical factors in the measurement of copy
      number concentrations by digital PCR is the partition volume. Therefore, we
      determined the average droplet volume by optical microscopy, revealing an average
      droplet volume that is 8 % smaller than the droplet volume used as the defined
      parameter in the QuantaSoft software version 1.3.2.0 (Bio-Rad) to calculate the
      copy number concentration. This observation explains why copy number
      concentrations estimated with ddPCR and using an average droplet volume
      predefined in the QuantaSoft software were systematically lower than those
      measured by dPCR, creating a significant bias between the values obtained by
      these two techniques. The difference was not significant anymore when the
      measured droplet volume of 0.834 nL was used to estimate copy number
      concentrations. A new version of QuantaSoft software (version 1.6.6.0320), which
      has since been released with Bio-Rad's new QX200 systems and QX100 upgrades, uses
      a droplet volume of 0.85 nL as a defined parameter to calculate copy number
      concentration. 

PMID- 25600687
TI  - High-resolution mass spectrometry provides novel insights into products of human
      metabolism of organophosphate and brominated flame retardants.
AB  - The high resolution, accurate mass, and fast scanning features of the
      Orbitrap(TM) mass spectrometer, combined with the separation power of ultrahigh
      performance liquid chromatography were applied for the first time to study the
      metabolic profiles of several organic flame retardants (FRs) present in indoor
      dust. To mimic real-life exposure, in vitro cultured HepG2 human hepatocyte cell
      lines were exposed simultaneously to various FRs in an indoor dust extract for 24
      h. Target parent FRs, hexabromocyclododecanes (alpha-, beta-, and gamma-HBCDs),
      tris-2-chloroethyl phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP),
      and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), were separated in a single
      run for the first time using alternating positive and negative heated ESI source.
      Further metabolite separation and identification was achieved using full scan
      (70,000 full width at half maximum (FWHM)), accurate mass (up to 1 ppm)
      spectrometry. Structural confirmation was performed via all ion fragmentation
      (AIF) spectra using the optional higher collisional dissociation (HCD) cell and
      MS/MS analysis. First insights into human metabolism of HBCDs revealed several
      hydroxylated and debrominated phase I metabolites, in addition to conjugated
      phase II glucuronides. Furthermore, various hydroxylated, oxidized, and
      conjugated metabolites of chlorinated phosphorous FRs were identified, leading to
      the suggestion of alpha-oxidation as a significant metabolic pathway for these
      compounds. 

PMID- 25600688
TI  - Quantification of plant surface metabolites by matrix-assisted laser desorption
      ionization mass spectrometry imaging: glucosinolates on Arabidopsis thaliana
      leaves.
AB  - The localization of metabolites on plant surfaces has been problematic because of
      the limitations of current methodologies. Attempts to localize glucosinolates,
      the sulfur-rich defense compounds of the order Brassicales, on leaf surfaces have
      given many contradictory results depending on the method employed. Here we
      developed a matrix-assisted laser desorption-ionization (MALDI) mass spectrometry
      protocol to detect surface glucosinolates on Arabidopsis thaliana leaves by
      applying the MALDI matrix through sublimation. Quantification was accomplished by
      spotting glucosinolate standards directly on the leaf surface. The A. thaliana
      leaf surface was found to contain approximately 15 nmol of total glucosinolate
      per leaf with about 50 pmol mm(-2) on abaxial (bottom) surfaces and 15-30 times
      less on adaxial (top) surfaces. Of the major compounds detected, 4
      methylsulfinylbutylglucosinolate, indol-3-ylmethylglucosinolate, and 8
      methylsulfinyloctylglucosinolate were also major components of the leaf interior,
      but the second most abundant glucosinolate on the surface, 4
      methylthiobutylglucosinolate, was only a trace component of the interior.
      Distribution on the surface was relatively uniform in contrast to the interior,
      where glucosinolates were distributed more abundantly in the midrib and periphery
      than the rest of the leaf. These results were confirmed by two other mass
      spectrometry-based techniques, laser ablation electrospray ionization and liquid
      extraction surface analysis. The concentrations of glucosinolates on A. thaliana
      leaf surfaces were found to be sufficient to attract the specialist feeding
      lepidopterans Plutella xylostella and Pieris rapae for oviposition. The methods
      employed here should be easily applied to other plant species and metabolites.

PMID- 25600689
TI  - Protective effect of L-carnitine on Phenylalanine-induced DNA damage.
AB  - The pathogenesis and the progression of phenylketonuria (PKU), an inborn error of
      phenylalanine (Phe) metabolism, have been associated with oxidative damage.
      Moreover, it has been increasingly postulated the antioxidant properties of L
      Carnitine (LC). The aim of this study was to verify the effect of LC on Phe
      induced DNA damage. The in vitro effect of different concentrations of LC (15,
      30, 120 and 150 MUM) on DNA damage-induced by high phenylalanine levels (1000 and
      2500 MUM) was examined in white blood cells from normal individuals using the
      comet assay. Urinary 8-hydroxydeoguanosine (8-OHdG) levels, a biomarker of
      oxidative DNA damage, and plasmatic sulfhydryl content were measured in eight
      patients with classical PKU, under therapy with protein restriction and
      supplemented with a special formula containing LC, and in controls individuals.
      Both in vitro tested Phe concentrations (1000 and 2500 MUM) have resulted in DNA
      damage index significantly higher than control group. The in vitro co-treatment
      with Phe and LC reduced significantly DNA damage index when compared to Phe
      group. The urinary excretion of 8-OHdG and plasmatic sulfhydryl content presented
      similar levels in both groups analyzed (controls and treated PKU patients). In
      treated PKU patients, urinary 8-OHdG levels were positively correlated with blood
      Phe levels and negatively correlated with blood LC concentration and plasmatic
      sulfhydryl content. The present work yields experimental evidence that LC can
      reduce the in vitro DNA injury induced by high concentrations of phenylalanine,
      as well as, allow to hypothesize that LC protect against DNA damage in patients
      with PKU. 

PMID- 25600695
TI  - Abrikossoff cell tumor of the esophagus: case presentation of a rare endoscopic
      entity and review of literature.

PMID- 25600690
TI  - The neuroprotective effect of berberine in mercury-induced neurotoxicity in rats.
AB  - The central nervous system is one of the most vulnerable organs affected by
      mercury toxicity. Both acute and chronic exposure to mercury is also known to
      cause a variety of neurological or psychiatric disorders. Here, the
      neuroprotective effect of berberine (BN; 100 mg/kg bwt) on mercuric chloride
      (HgCl2; 0.4 mg/kg bwt) induced neurotoxicity and oxidative stress was examined in
      rats. Adult male albino Wistar rats were injected with HgCl2 for 7 days. HgCl2
      treatment induced oxidative stress by increasing lipid peroxidation (LPO) and
      nitrite/nitrate (nitric oxide; NO) production along with a concomitant decrease
      in glutathione (GSH) and various antioxidant enzymes, namely superoxide
      dismutase, catalase, glutathione peroxidase and glutathione reductase. Pre
      treatment of rats with BN inhibited LPO and NO production, whereas it increased
      GSH content. Activities of antioxidant enzymes were also restored concomitantly
      when compared to the control rats after BN administration. Berberine also caused
      decrease in TNF-alpha level and caspase-3 activity which was higher with HgCl2.
      Furthermore, treatment with BN inhibited apoptosis, as indicated by the reduction
      of Bax/Bcl-2 ratio in brain tissue. These data indicated that BN augments
      antioxidant defense with anti-inflammatory and anti-apoptotic activities against
      HgCl2-induced neurotoxicity and provides evidence that it has a therapeutic
      potential as neuroprotective agent. 

PMID- 25600691
TI  - Houttuynia cordata modulates oral innate immune mediators: potential role of
      herbal plant on oral health.
AB  - OBJECTIVE: Epithelial cells play an active role in oral innate immunity by
      producing various immune mediators. Houttuynia cordata Thunb (H. cordata), a
      herbal plant found in Asia, possesses many activities. However, its impacts on
      oral innate immunity have never been reported. The aim of this study was to
      determine the effects of H. cordata extract on the expression of innate immune
      mediators produced by oral epithelial cells. MATERIALS AND METHODS: Primary
      gingival epithelial cells (GECs) were treated with various concentrations of the
      extract for 18 h. The gene expression of hBD2, SLPI, cytokines, and chemokines
      was measured using quantitative real-time RT-PCR. The secreted proteins in the
      culture supernatants were detected by ELISA or Luminex assay. Cytotoxicity of the
      extract was assessed using CellTiter-Blue Assay. RESULTS: H. cordata
      significantly induced the expression of hBD2, SLPI, IL-8, and CCL20 in a dose
      dependent manner without cytotoxicity. The secreted hBD2 and SLPI proteins were
      modulated, and the levels of IL-2, IL-6, IL-8, and IFN-gamma were significantly
      induced by the extract. CONCLUSIONS: Our data indicated that H. cordata can
      modulate oral innate immune mediators. These findings may lead to the development
      of new topical agents from H. cordata for the prevention and treatment of immune
      mediated oral diseases.

PMID- 25600696
TI  - High membrane protein oxidation in the human cerebral cortex.
AB  - Oxidative stress is thought to be one of the main mediators of neuronal damage in
      human neurodegenerative disease. Still, the dissection of causal relationships
      has turned out to be remarkably difficult. Here, we have analyzed global protein
      oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins
      in three different mammalian species: aged human cortex and cerebellum from
      patients with or without Alzheimer's disease, mouse cortex and cerebellum from
      young and old animals, and adult rat hippocampus and cortex subjected or not
      subjected to cerebral ischemia. Most tissues showed relatively similar levels of
      protein oxidation. However, human cortex was affected by severe membrane protein
      oxidation, while exhibiting lower than average cytoplasmic protein oxidation. In
      contrast, ex vivo autooxidation of murine cortical tissue primarily induced
      aqueous protein oxidation, while in vivo biological aging or cerebral ischemia
      had no major effect on brain protein oxidation. The unusually high levels of
      membrane protein oxidation in the human cortex were also not predicted by lipid
      peroxidation, as the levels of isoprostane immunoreactivity in human samples were
      considerably lower than in rodent tissues. Our results indicate that the aged
      human cortex is under steady pressure from specific and potentially detrimental
      membrane protein oxidation. The pronounced difference between humans, mice and
      rats regarding the primary site of cortical oxidation might have contributed to
      the unresolved difficulties in translating into therapies the wealth of data
      describing successful antioxidant neuroprotection in rodents. 

PMID- 25600697
TI  - siRNA induces gelsolin gene transcription activation in human esophageal cancer
      cell.
AB  - Recent studies show that targeting gene promoter or 3' terminal regions of mRNA
      with siRNA induces target gene transcription. However, the ability of exon
      targeting siRNA to affect transcription has yet to be demonstrated. We designed
      and synthesized siRNA against various exons in the gelsolin gene (GSN) to
      knockdown GSN transcript in KYSE150 and KYSE450 cells. Surprisingly, we found
      that siGSN-2, targeting the GSN twelfth exon, induced GSN gene transcription
      detected by real time RT-PCR. An siGSN-2 co-precipitation assay was performed and
      H3 histone, previously shown to correlate with gene transcription, was detected
      in the siGSN-2 pull-down pellet. However, H3 histone was not detected in an siGSN
      1-precipitated pellet, which resulted in GSN knockdown. In addition, siGSN-2
      decreased stress fibers, lamellipodia and filopodia, demonstrating that siGSN-2
      induced GSN transcription activation and exerted biological function. In
      conclusion, our finds reveal siRNA, which is derived from target gene exon, can
      form the complex with H3 histone to be involved in the regulation of gene
      expression. 

PMID- 25600698
TI  - Ryanodine and inositol triphosphate receptors modulate facilitation and tetanic
      depression at the frog neuromuscular junction.
AB  - INTRODUCTION: Short-term plasticity of synaptic function is an important
      physiological control of transmitter release. Short-term plasticity can be
      regulated by intracellular calcium released by ryanodine and inositol
      triphosphate (IP3) receptors, but the role of these receptors at the
      neuromuscular junction is understood incompletely. METHODS: We measured short
      term plasticity of evoked endplate potential (EPP) amplitudes from frog
      neuromuscular junctions treated with ryanodine, 2-aminoethoxydiphenylborane (2
      APB), or 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H
      pyrrole-2,5-dione (U- 73122). RESULTS: Ryanodine decreases paired-pulse
      facilitation for intervals <20 ms and markedly decreases tetanic depression.
      Treatment with 2-APB reduces EPP amplitude, increases paired-pulse facilitation
      for intervals of <20 ms, and significantly reduces tetanic depression. U-73122
      decreases EPP amplitude and decreases paired-pulse depression for intervals <20
      ms. CONCLUSIONS: Ryanodine, IP3 receptors, and phospholipase C modulate short
      term plasticity of transmitter release at the neuromuscular junction. These
      results suggest possible targets for improving the safety factor of neuromuscular
      transmission during repetitive activity of the neuromuscular junction.

PMID- 25600699
TI  - [How does the brain control eye movements? Motor and premotor neurons of the
      brainstem].
AB  - Knowledge of cognitive and neural architecture and processes that control eye
      movements has advanced enough to allow precise and quantitative analysis of
      hitherto unsolved phenomena. In this review, we revisit from a neuropsychological
      viewpoint Hering vs. Helmholtz' hypotheses on binocular coordination.
      Specifically, we reexamine the behavior and the neural bases of saccade-vergence
      movement, to move the gaze in both direction and depth under natural conditions.
      From the psychophysical viewpoint, neo-Heringian and neo-Helmholtzian authors
      have accumulated arguments favoring distinct conjugate (for saccades) and
      disconjugate (for vergence) systems, as well as advocating for monocularly
      programmed eye movements. From the neurophysiological viewpoint, which reports
      brain cell recordings during the execution of a given task, neo-Heringian and neo
      Helmholtzian physiologists have also provided arguments in favor of both
      hypotheses at the level of the brainstem premotor circuitry. Bridging the two, we
      propose that Hering and Helmholtz were both right. The emphasis placed by the
      latter on adaptive processes throughout life cycle is compatible with the
      importance of neurobiological constraints pointed out by the former. In the
      meanwhile, the study of saccade-vergence eye movements recalls how much the
      psychophysical definition of the task determines the interpretation that is made
      from neurophysiological data. 

PMID- 25600700
TI  - Paralytic ileus following "subcutaneous bortezomib" therapy: focus on the
      clinical emergency-report of two cases.
AB  - We retrospectively analyzed the medical history of 19 elderly myeloma patients
      treated with the "novel subcutaneous formulation of bortezomib." In our
      experience, two patients (10 %) discontinued treatment for paralytic ileus. The
      exact pathogenetic mechanisms of toxic megacolon and paralytic ileus due to
      "novel subcutaneous formulation of bortezomib" are unclear. Probably, it may be
      related to possible damage of the autonomic nerve fibers that control organ
      functions. Adequate prevention and management of the gastrointestinal (GI)
      toxicities with the use of fluid intake and prokinetic and laxative drugs (at
      least two types of agents in a suboptimal dose) especially in patients with risk
      factors for GI side effects (anti-myeloma novel agents, opioids or antiemetics,
      iron supplements, spinal and cord compression, immobility, history of
      constipation) can decrease the possibility of interruption of administration of
      drug and increase adherence to treatment. Clearly this complication must be borne
      in mind whenever a patient develops acute abdominal pain and distension.

PMID- 25600701
TI  - Glucosepane and oxidative markers in skin collagen correlate with intima media
      thickness and arterial stiffness in long-term type 1 diabetes.
AB  - AIMS: To study intima media thickness (cIMT) and arterial stiffness in type 1
      diabetes of long duration, and their associations with the collagen cross-linker
      glucosepane and inflammatory and oxidative markers. METHODS: Twenty-seven
      individuals with type 1 diabetes mellitus of 40 years duration from the Oslo
      Study cohort and 24 age-matched controls were included. cIMT measurements of the
      carotid artery were performed longitudinally. Pulse wave velocity (PWV),
      augmentation index (AIx) and augmentation pressure (AP) were assessed cross
      sectionally. Glucosepane and the oxidative product methionine sulfoxide (MetSO)
      were determined in skin collagen by liquid chromatography-mass spectrometry.
      Circulating inflammatory markers were determined by ELISAs. RESULTS: The diabetes
      patients had significantly increased cIMT and arterial stiffness compared to
      controls. Significant correlations were noted for skin glucosepane with cIMT
      (r=0.41) and PWV (r=0.44). Skin MetSO and monocyte chemoattractant protein-1 (MCP
      1) correlated significantly with AIx and AP. After correcting for age and mean
      arterial pressure in multiple linear regression analysis, MetSO and MCP-1 were
      both independently associated with AIx and AP. CONCLUSIONS: These results suggest
      more premature atherosclerosis and arterial pathology in individuals with
      diabetes compared to age-matched controls. They also suggest an association
      between the arterial pathology and markers of collagen crosslinking, oxidative
      damage and inflammation in type 1 diabetes patients of forty years disease
      duration.

PMID- 25600702
TI  - Mesenchymal stem cells modified with nerve growth factor improve recovery of the
      inferior alveolar nerve after mandibular distraction osteogenesis in rabbits.
AB  - Distraction osteogenesis is widely used in the treatment of bony deformities and
      defects. However, injury to the inferior alveolar nerve is a concern. Our aim was
      to investigate the feasibility of using lentiviral-mediated human nerve growth
      factor beta (hNGFbeta) of the inferior alveolar nerve in mandibular distraction
      osteogenesis in rabbits. To achieve this, mesenchymal stem cells (MSC) from the
      bone marrow of rabbit mandibles were isolated and genetically engineered using
      recombinant lentiviral vector containing hNGFbeta. Twenty New Zealand white
      rabbits underwent mandibular distraction osteogenesis, and 5 million MSC
      transduced with hNGFbeta-vector or control vector were transplanted around the
      nerve in the gap where the bone had been fractured during the operation (n=10 in
      each group). After gradual distraction, samples of the nerve were harvested for
      histological and histomorphometric analysis. We found that the genetically
      engineered MSC transduced by the lentiviral vector were able to secrete hNGFbeta
      at physiologically relevant concentrations as measured by ELISA. Histological
      examination of the nerve showed more regenerating nerve fibres and less myelin
      debris in the group in which hNGFbeta-modified MSC had been implanted than in the
      control group. Histomorphometric analysis of the nerve showed increased density
      of myelinated fibres in the group in which hNGFbeta-modified MSC had been
      implanted than in the control group. The data suggest that implantation of
      hNGFbeta-modified MSC can accelerate the morphological recovery of the inferior
      alveolar nerve during mandibular distraction osteogenesis in rabbits. The use of
      lentiviral-mediated gene treatment to deliver hNGFbeta through MSC may be a
      promising way of minimising injury to the nerve.

PMID- 25600703
TI  - Four types of ipsilateral breast tumor recurrence (IBTR) after breast-conserving
      surgery: classification of IBTR based on precise pathological examination.
AB  - We classified ipsilateral breast tumor recurrences (IBTRs) based on strict
      pathological rules. Ninety-six women who were surgically treated for IBTR were
      included. IBTRs were classified according to their origins and were distinguished
      based on strict pathological rules: relationship between the IBTR and the primary
      lumpectomy scar, surgical margin status of the primary cancer, and the presence
      of in situ lesions of IBTR. The prognosis of these subgroups were compared to
      that of new primary tumors (NP) in the narrow sense (NPn) that occurred far from
      the scar. Distant-disease free survival of IBTR that occurred close to the scar
      with in situ lesions and a negative surgical margin of the primary cancer (NP
      occurred close to the scar, NPcs) was similar to that of NPn. In contrast, IBTR
      that occurred close to the scar without in situ lesions (true recurrence (TR)
      that arose from residual invasive carcinoma foci, TRinv) had significantly poorer
      prognosis than NPn. IBTR that occurred close to the scar with in situ lesions and
      a positive surgical margin of the primary cancer (TR arising from a residual in
      situ lesion, TRis) had more late recurrences than NPcs. Precise pathological
      examinations indicated four distinct IBTR subtypes with different
      characteristics. 

PMID- 25600704
TI  - Multi-stage methodology to detect health insurance claim fraud.
AB  - Healthcare costs in the US, as well as in other countries, increase rapidly due
      to demographic, economic, social, and legal changes. This increase in healthcare
      costs impacts both government and private health insurance systems. Fraudulent
      behaviors of healthcare providers and patients have become a serious burden to
      insurance systems by bringing unnecessary costs. Insurance companies thus develop
      methods to identify fraud. This paper proposes a new multistage methodology for
      insurance companies to detect fraud committed by providers and patients. The
      first three stages aim at detecting abnormalities among providers, services, and
      claim amounts. Stage four then integrates the information obtained in the
      previous three stages into an overall risk measure. Subsequently, a decision tree
      based method in stage five computes risk threshold values. The final decision
      stating whether the claim is fraudulent is made by comparing the risk value
      obtained in stage four with the risk threshold value from stage five. The
      research methodology performs well on real-world insurance data. 

PMID- 25600706
TI  - High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal
      microbiota after radiotherapy.
AB  - The mammalian gastrointestinal tract harbors a highly complex microbial community
      that comprises hundreds of different types of bacterial cells. The
      gastrointestinal microbiota plays an important role in the function of the host
      intestine. Most cancer patients undergoing pelvic irradiation experience side
      effects such as diarrhea; however, little is currently known about the effects of
      irradiation on the microorganisms colonizing the mucosal surfaces of the
      gastrointestinal tract. The aim of this study was to investigate the effects of
      gamma irradiation on the compositions of the large and small intestinal
      microbiotas. The gut microbiotas in control mice and mice receiving irradiation
      treatment were characterized by high-throughput sequencing of the bacterial 16S
      rRNA gene. Irradiation treatment induced significant alterations in the bacterial
      compositions of the large and small intestines at the genus level. Unexpectedly,
      irradiation treatment increased the number of operational taxonomic units in the
      small intestine but not the large intestine. In particular, irradiation treatment
      increased the level of the genera Alistipes in the large intestine and increased
      the level of the genus Corynebacterium in the small intestine. By contrast,
      compared with that in the corresponding control group, the level of the genera
      Prevotella was lower in the irradiated large intestine, and the level of the
      genera Alistipes was lower in the irradiated small intestine. Overall, the data
      presented here reveal the potential microbiological effects of pelvic irradiation
      on the gastrointestinal tracts of cancer patients. 

PMID- 25600705
TI  - Deficiency of fibroblast activation protein alpha ameliorates cartilage
      destruction in inflammatory destructive arthritis.
AB  - INTRODUCTION: Inflammatory destructive arthritis, like rheumatoid arthritis (RA),
      is characterized by invasion of synovial fibroblasts (SF) into the articular
      cartilage and erosion of the underlying bone, leading to progressive joint
      destruction. Because fibroblast activation protein alpha (FAP) has been
      associated with cell migration and cell invasiveness, we studied the function of
      FAP in joint destruction in RA. METHODS: Expression of FAP in synovial tissues
      and fibroblasts from patients with osteoarthritis (OA) and RA as well as from
      wild-type and arthritic mice was evaluated by immunohistochemistry, fluorescence
      microscopy and polymerase chain reaction (PCR). Fibroblast adhesion and migration
      capacity was assessed using cartilage attachment assays and wound-healing assays,
      respectively. For in vivo studies, FAP-deficient mice were crossed into the human
      tumor necrosis factor transgenic mice (hTNFtg), which develop a chronic
      inflammatory arthritis. Beside clinical assessment, inflammation, cartilage
      damage, and bone erosion were evaluated by histomorphometric analyses. RESULTS:
      RA synovial tissues demonstrated high expression of FAP whereas in OA samples
      only marginal expression was detectable. Consistently, a higher expression was
      detected in arthritis SF compared to non-arthritis OA SF in vitro. FAP-deficiency
      in hTNFtg mice led to less cartilage degradation despite unaltered inflammation
      and bone erosion. Accordingly, FAP(-/-) hTNFtg SF demonstrated a lower cartilage
      adhesion capacity compared to hTNFtg SF in vitro. CONCLUSIONS: These data point
      to a so far unknown role of FAP in the attachment of SF to cartilage, promoting
      proteoglycan loss and subsequently cartilage degradation in chronic inflammatory
      arthritis.

PMID- 25600707
TI  - Editorial: Introduction to 'beneficial effects of psychedelics with a special
      focus on addictions'.

PMID- 25600709
TI  - Phylogeny and systematics of deep-sea precious corals (Anthozoa: Octocorallia:
      Coralliidae).
AB  - The phylogeny of Coralliidae is being increasingly studied to elucidate their
      evolutionary history and species delimitation due to global concerns about their
      conservation. Previous studies on phylogenetic relationships within Coralliidae
      have pointed out that the two currently recognized genera are not monophyletic
      and the Coralliidae should be divided into three genera. In order to provide a
      comprehensive revision of the taxonomy of Coralliidae, we documented 110
      specimens using eight mitochondrial and one nuclear loci to reconstruct their
      phylogeny. The morphological features of 27 type specimens were also examined.
      Phylogenetic relationships based on both mitochondrial and nuclear markers
      revealed two reciprocally monophyletic clades of Coralliidae. One of the clades
      was further split into two subclades with respect to sequence variation and
      observable morphological features. Based on the results of genealogical analyses
      and distinctive morphological features, the three genera classification of
      Coralliidae proposed by Gray (1867) was redefined. In this revised taxonomic
      system, Corallium, Hemicorallium, and Pleurocorallium consist of 7, 16 and 14
      species, respectively. Our results also showed that the cosmopolitan
      Hemicorallium laauense is a species complex containing a cryptic species. 

PMID- 25600708
TI  - Defective hCNT1 transport contributes to gemcitabine chemoresistance in ovarian
      cancer subtypes: overcoming transport defects using a nanoparticle approach.
AB  - Nucleoside analogs are used as chemotherapeutic options for the treatment of
      platinum-resistant ovarian cancers. Human concentrative nucleoside transporter 1
      (hCNT1) is implicated in sensitizing solid tumors to nucleoside analogs although
      its role in determining drug efficacy in ovarian cancers remains unclear. Here we
      examined the functional expression of hCNT1 and compared its contributions toward
      gemcitabine efficacy in histological subtypes of ovarian cancer. Radioactivity
      analysis identified hCNT1-mediated (3)H-gemcitabine transport in ovarian cancer
      cells to be significantly reduced compared with that of normal ovarian surface
      epithelial cells. Biochemical and immunocytochemical analysis identified that
      unlike normal ovarian cells which expressed high levels of hCNT1 at the apical
      cell surface, the transporter was either diminished in expression and/or
      mislocalized in cell lines of various subtypes of ovarian cancer. Retroviral
      expression of hCNT1 selectively rescued gemcitabine transport in cell lines
      representing serous, teratocarcinoma, and endometrioid subtypes, but not clear
      cell carcinoma (CCC). In addition, exogenous hCNT1 predominantly accumulated in
      intracytoplasmic vesicles in CCC suggesting defective cellular trafficking of
      hCNT1 as a contributing factor to transport deficiency. Despite diminution of
      hCNT1 transport in the majority of ovarian cancers and apparent trafficking
      defects with CCC, the chemotherapeutic efficacy of gemcitabine was broadly
      enhanced in all subtypes when delivered via engineered nanoparticles (NPs).
      Additionally, by bypassing the transport requirement, the delivery of a
      gemcitabine-cisplatin combination in NP formulation increased their synergistic
      interactions. These findings uncover hCNT1 as a putative determinant for
      nucleoside analog chemoresistance in ovarian cancer and may help rationalize drug
      selection and delivery strategies for various histological subtypes of ovarian
      cancer. 

PMID- 25600710
TI  - Towards social radiology as an information infrastructure: reconciling the local
      with the global.
AB  - The current widespread use of medical images and imaging procedures in clinical
      practice and patient diagnosis has brought about an increase in the demand for
      sharing medical imaging studies among health professionals in an easy and
      effective manner. This article reveals the existence of a polarization between
      the local and global demands for radiology practice. While there are no major
      barriers for sharing such studies, when access is made from a (local) picture
      archive and communication system (PACS) within the domain of a healthcare
      organization, there are a number of impediments for sharing studies among health
      professionals on a global scale. Social radiology as an information
      infrastructure involves the notion of a shared infrastructure as a public good,
      affording a social space where people, organizations and technical components may
      spontaneously form associations in order to share clinical information linked to
      patient care and radiology practice. This article shows however, that such
      polarization establishes a tension between local and global demands, which
      hinders the emergence of social radiology as an information infrastructure. Based
      on an analysis of the social space for radiology practice, the present article
      has observed that this tension persists due to the inertia of a locally installed
      base in radiology departments, for which common teleradiology models are not
      truly capable of reorganizing as a global social space for radiology practice.
      Reconciling the local with the global signifies integrating PACS and
      teleradiology into an evolving, secure, heterogeneous, shared, open information
      infrastructure where the conceptual boundaries between (local) PACS and (global)
      teleradiology are transparent, signaling the emergence of social radiology as an
      information infrastructure. 

PMID- 25600711
TI  - Equilibrated atomic models of outward-facing P-glycoprotein and effect of ATP
      binding on structural dynamics.
AB  - P-glycoprotein (Pgp) is an ATP-binding cassette (ABC) transporter that alternates
      between inward- and outward-facing conformations to capture and force substrates
      out of cells like a peristaltic pump. The high degree of similarity in outward
      facing structures across evolution of ABC transporters allowed construction of a
      high-confidence outward-facing Pgp atomic model based on crystal structures of
      outward-facing Sav1866 and inward-facing Pgp. The model adhered to previous
      experimentally determined secondary- and tertiary- configurations during all-atom
      molecular dynamics simulations in the presence or absence of MgATP. Three long
      lasting (>100 ns) meta-stable states were apparent in the presence of MgATP
      revealing new insights into alternating access. The two ATP-binding pockets are
      highly asymmetric resulting in differential control of overall structural
      dynamics and allosteric regulation of the drug-binding pocket. Equilibrated Pgp
      has a considerably different electrostatic profile compared to Sav1866 that
      implicates significant kinetic and thermodynamic differences in transport
      mechanisms. 

PMID- 25600712
TI  - External urethral sphincter electromyography in asymptomatic women and the
      influence of the menstrual cycle.
AB  - OBJECTIVE: To investigate by electromyography (EMG), the presence of complex
      repetitive discharges (CRDs) and decelerating bursts (DBs) in the striated
      external urethral sphincter during the menstrual cycle in female volunteers with
      no urinary symptoms and complete bladder emptying. SUBJECTS AND METHODS: Healthy
      female volunteers aged 20-40 years, with regular menstrual cycles and no urinary
      symptoms were recruited. Volunteers completed a menstruation chart, urinary
      symptom questionnaires, pregnancy test, urine dipstick, urinary free flow and
      post-void ultrasound bladder scan. Exclusion criteria included current pregnancy,
      use of hormonal medication or contraception, body mass index of >35 kg/m(2) ,
      incomplete voiding and a history of pelvic surgery. Eligible participants
      underwent an external urethral sphincter EMG, using a needle electrode in the
      early follicular phase and the mid-luteal phase of their menstrual cycles. Serum
      oestradiol and progesterone were measured at each EMG test. RESULTS: In all, 119
      women enquired about the research and following screening, 18 were eligible to
      enter the study phase. Complete results were obtained in 15 women. In all, 30 EMG
      tests were undertaken in the 15 asymptomatic women. Sphincter EMG was positive
      for CRDs and DBs at one or both phases of the menstrual cycle in eight (53%) of
      the women. Three had CRDs and DBs in both early follicular and mid-luteal phases.
      Five had normal EMG activity in the early follicular phase and CRDs and DBs in
      the mid-luteal phase. No woman had abnormal EMG activity in the early follicular
      phase and normal activity in the luteal phase. There was no relationship between
      EMG activity and age, parity or serum levels of oestradiol and progesterone.
      CONCLUSIONS: CRDs and DB activity in the external striated urethral sphincter is
      present in a high proportion of asymptomatic young women. This abnormal EMG
      activity has been shown for the first time to change during the menstrual cycle
      in individual women. CRDs and DBs are more commonly found in the luteal phase of
      the menstrual cycle. The importance of CRDs and DBs in the aetiology of urinary
      retention in young women remains uncertain. The distribution and or quantity of
      abnormal EMG activity in the external urethral sphincter may be important. In a
      woman with urinary retention the finding of CRDs and DBs by needle EMG does not
      automatically establish Fowler's syndrome as the explanation for the bladder
      dysfunction. Urethral pressure profilometry may be helpful in establishing a
      diagnosis. Opiate use and psychological stress should be considered in young
      women with urinary retention.

PMID- 25600713
TI  - The variability of standard artificial soils: effects on the survival and
      reproduction of springtail (Folsomia candida) and potworm (Enchytraeus
      crypticus).
AB  - Recent studies have documented significant variability in the basic properties of
      artificial soil which is used as a standard medium in soil bioassays. Variability
      in key soil properties could confound the interpretation of toxicity data and
      bias the output of bioassays. The main aims of this study were (i) to identify
      the variability in the endpoints survival and reproduction of Folsomia candida
      and Enchytraeus crypticus related to the artificials soils prepared in different
      laboratories and (ii) to identify the specific physico-chemical properties of the
      artificial soils which influence the bioassays results. The results of
      reproduction tests showed that nearly all tested artificial soils were suitable
      for the survival and reproduction of both organisms as the validity criteria from
      the test standards were fulfilled. However, numbers of juveniles varied
      significantly among soils. The most important factor for F. candida performance
      was a coarser soil structure. C:N ratio (<22.6) were important for the
      reproduction of E. crypticus. Both species tolerated a pH (KCl) of artificial
      soils in the range of 4.27-6.8 and even low TOC (1.5%). Thus, it is possible to
      reduce peat content in artificial soils, which may increase the comparability of
      results to those for natural soils. 

PMID- 25600714
TI  - The detoxification process, bioaccumulation and damage effect in juvenile white
      shrimp Litopenaeus vannamei exposed to chrysene.
AB  - This study aimed to evaluate the effect of chrysene (CHR) on detoxification
      enzymes, bioaccumulation and effect of CHR on biomolecule damage in different
      organs of the juvenile white shrimp Litopenaeus vannamei. In this study, juvenile
      white shrimp L. vannamei were exposed to CHR for 21 days at four different
      concentrations as 0, 0.3, 2.1 and 14.7 MUg/L. Results showed that CHR
      bioaccumulation increased rapidly at first then reached a plateau. The activities
      of aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD),
      epoxide hydrolase (EH), glutathione-S-transferase (GST), sulfotransferase (SULT)
      and uridinediphosphate glucuronyltransferase (UGT) were induced and then became
      stable gradually. Moreover, 2.1 and 14.7 MUg/L CHR treatments increased activity
      of superoxide dismutase (SOD) in gills and hepatopancreas, while total
      antioxidant capacity (T-AOC) and GSH/GSSG were suppressed after CHR exposure.
      Additionally, lipid peroxidation (LPO) levels, protein carbonyl (PC) contents and
      DNA damage were induced throughout the exposure period, and different trends were
      detected with time of exposure. Overall, these novel findings of CHR
      bioaccumulation and resulted toxicity demonstrate that CHR could affect the
      physical status of L. vannamei. This study will form a solid basis for a
      realistic extrapolation scientific data for aquaculture water monitoring and food
      security.

PMID- 25600715
TI  - Detoxification and color removal of Congo red by a novel Dietzia sp. (DTS26) - a
      microcosm approach.
AB  - The present study deals with the decolorization and detoxification of Congo red
      (CR) by a novel marine bacterium Dietzia sp. (DTS26) isolated from Divar Island,
      Goa, India. The maximum decolorization of 94.5% (100 mg L(-1)) was observed under
      static condition within 30 h at pH 8 and temperature 32+/-2 degrees C.
      Bacterially treated samples could enhance the light intensity by 38% and the
      primary production levels 5 times higher than the untreated. The strain was also
      able to reduce COD by 86.4% within 30 h at 100 mg L(-1) of CR dye. The degraded
      metabolites of CR dye were analyzed by FTIR, HPLC, GC-MS and the end product
      closely matches with 4-amino-3-naphthol-1-sulfonate which is comparatively less
      toxic than CR. Bioassay experiments conducted in treated samples for Artemia
      franciscana showed better survival rates (after 72 h) at higher concentration of
      CR (500 mg L(-1)). This work suggests the potential application of DTS26 in
      bioremediation of dye wastes and its safe disposal into coastal environment.

PMID- 25600716
TI  - Mercury concentrations in eggshells of the Southern Ground-Hornbill (Bucorvus
      leadbeateri) and Wattled Crane (Bugeranus carunculatus) in South Africa.
AB  - In this study, wild hatched eggshells were collected from the nests of threatened
      Wattled Crane and South Ground-Hornbill in an attempt to determine their total Hg
      concentrations. A total of fourteen eggshell samples from both bird species were
      collected from different study areas in the Mpumlanga and KwaZulu-Natal Provinces
      of South Africa. The eggshells were acid digested under reflux and their total Hg
      concentrations were determined using cold-vapour atomic absorption
      spectrophotometry (CV-AAS). The observed total Hg levels for the South Ground
      Hornbill samples ranged from 1.31 to 8.88 ug g(-1) dry weight (dw), except for
      one outlier which had an elevated 75.0 ug g(-1) dw. The levels obtained for the
      Wattled Crane samples were relatively high and these ranged from 14.84 to 36.37
      ug g(-1) dw. Generally, all the measured total Hg concentrations for the Wattled
      Crane samples exceeded the estimated total Hg levels derived for eggshell which
      were known to cause adverse reproductive effects in avian species from previous
      studies. Based on these findings, it is, therefore, possible that the exposure of
      these birds to elevated Hg may have contributed to their present population
      decline.

PMID- 25600717
TI  - Acute migraine treatment.

PMID- 25600718
TI  - The acute treatment of migraine in adults: the american headache society evidence
      assessment of migraine pharmacotherapies.
AB  - The study aims to provide an updated assessment of the evidence for individual
      pharmacological therapies for acute migraine treatment. Pharmacological therapy
      is frequently required for acutely treating migraine attacks. The American
      Academy of Neurology Guidelines published in 2000 summarized the available
      evidence relating to the efficacy of acute migraine medications. This review,
      conducted by the members of the Guidelines Section of the American Headache
      Society, is an updated assessment of evidence for the migraine acute medications.
      A standardized literature search was performed to identify articles related to
      acute migraine treatment that were published between 1998 and 2013. The American
      Academy of Neurology Guidelines Development procedures were followed. Two authors
      reviewed each abstract resulting from the search and determined whether the full
      manuscript qualified for review. Two reviewers studied each qualifying full
      manuscript for its level of evidence. Level A evidence requires at least 2 Class
      I studies, and Level B evidence requires 1 Class I or 2 Class II studies. The
      specific medications - triptans (almotriptan, eletriptan, frovatriptan,
      naratriptan, rizatriptan, sumatriptan [oral, nasal spray, injectable,
      transcutaneous patch], zolmitriptan [oral and nasal spray]) and dihydroergotamine
      (nasal spray, inhaler) are effective (Level A). Ergotamine and other forms of
      dihydroergotamine are probably effective (Level B). Effective nonspecific
      medications include acetaminophen, nonsteroidal anti-inflammatory drugs (aspirin,
      diclofenac, ibuprofen, and naproxen), opioids (butorphanol nasal spray),
      sumatriptan/naproxen, and the combination of acetaminophen/aspirin/caffeine
      (Level A). Ketoprofen, intravenous and intramuscular ketorolac, flurbiprofen,
      intravenous magnesium (in migraine with aura), and the combination of
      isometheptene compounds, codeine/acetaminophen and tramadol/acetaminophen are
      probably effective (Level B). The antiemetics prochlorperazine, droperidol,
      chlorpromazine, and metoclopramide are probably effective (Level B). There is
      inadequate evidence for butalbital and butalbital combinations, phenazone,
      intravenous tramadol, methadone, butorphanol or meperidine injections, intranasal
      lidocaine, and corticosteroids, including dexamethasone (Level C). Octreotide is
      probably not effective (Level B). There is inadequate evidence to refute the
      efficacy of ketorolac nasal spray, intravenous acetaminophen, chlorpromazine
      injection, and intravenous granisetron (Level C). There are many acute migraine
      treatments for which evidence supports efficacy. Clinicians must consider
      medication efficacy, potential side effects, and potential medication-related
      adverse events when prescribing acute medications for migraine. Although opioids,
      such as butorphanol, codeine/acetaminophen, and tramadol/acetaminophen, are
      probably effective, they are not recommended for regular use. 

PMID- 25600719
TI  - The prevalence and burden of migraine and severe headache in the United States:
      updated statistics from government health surveillance studies.
AB  - BACKGROUND AND OBJECTIVES: The US National Center for Health Statistics, which is
      part of the Centers for Disease Control, conducts ongoing public health
      surveillance activities. The US Armed Forces also maintains a comprehensive
      database of medical information. We aimed to identify the most current prevalence
      estimates of migraine and severe headache in the United States adult civilian and
      active duty service populations from these national government surveys, to assess
      stability of prevalence estimates over time, and to identify additional
      information pertinent to the burden and treatment of migraine and other severe
      headache conditions. METHODS: We searched for the most current publicly available
      summary statistics from the National Ambulatory Medical Care Survey, the National
      Hospital Ambulatory Medical Care Survey, and the National Health Interview Survey
      (NHIS). Summary data from the Defense Medical Surveillance System were also
      obtained, and PubMed was also searched for publications reporting summary
      statistics based on these studies. Data were abstracted, double-checked for
      accuracy, and summarized over time periods and as a function of demographic
      variables. RESULTS: 14.2% of US adults 18 or older reported having migraine or
      severe headache in the previous 3 months in the 2012 NHIS. The overall age
      adjusted 3-month prevalence of migraine in females was 19.1% and in males 9.0%,
      but varied substantially depending on age. The prevalence of migraine was highest
      in females 18-44, where the 3-month prevalence of migraine or severe headache was
      23.5%. The 3-month prevalence of migraine or severe headache has remained
      relatively stable over the period of2005-2012, with an average prevalence of
      20.2% in females, 9.4% in males, and 14.9% overall [corrected]. During this time,
      the average female to male sex ratio for migraine or severe headache was 2.17.
      The unadjusted 1-year prevalence of migraine in active duty US military service
      members varied from 1% to 1.9% between 1998 and 2010, ranging from 0.7% to 1.2%
      in males and 3.5% to 6% in females. The 1-year prevalence of "other headache" in
      this military population ranged from a low of 1.9% in 2003 to a high of 3% in
      2010. Headache or pain in the head was the fourth leading cause of visits to the
      emergency department (ED) in 2009-2010, accounting for 3.1% of all ED visits.
      Across all ambulatory care settings, migraine accounted for 0.5% of all visits
      and other headache presentations for 0.4% of all ambulatory care visits. 52.8% of
      all visits for migraine occurred in primary care settings, 23.2% in specialty
      outpatient settings, and 16.7% in EDs. In 2010, opioids were administered at 35%
      of ED visits for headache, while triptans were administered in only 1.5% of
      visits. CONCLUSIONS: This report summarizes the most recent government statistics
      on the prevalence and burden of migraine and severe headache in the US civilian
      and active duty military populations. The prevalence of migraine headaches is
      high, affecting roughly 1 out of every 7 Americans annually, and has remained
      relatively stable over the last 8 years. Migraine and headache are leading causes
      of outpatient and ED visits and remain an important public health problem,
      particularly among women during their reproductive years.

PMID- 25600720
TI  - Celecoxib vs prednisone for the treatment of withdrawal headache in patients with
      medication overuse headache: a randomized, double-blind clinical trial.
AB  - OBJECTIVE: To compare the efficacy of celecoxib for treatment of withdrawal
      headache vs prednisone in patients with medication overuse headache (MOH).
      METHODS: In this prospective, double-blind, parallel-group clinical trial, 97
      consecutive subjects with MOH were randomized (simple randomization using
      computer-generated numbers) for treatment with either 400 mg/day celecoxib (for
      the first 5 days then decreased at a rate of 100 mg every 5 days) or prednisone
      75 mg/day orally (for the first 5 days then tapered off every 5 days). Subjects
      who met the International Headache Society criteria for MOH were included in the
      trial. The change in headache days and intake of rescue medication were
      considered as primary outcomes while the change in headache severity defined as a
      secondary outcome. RESULTS: Patients treated with celecoxib experienced lower
      headache intensity during the first 3 weeks after withdrawal (after 3 weeks, the
      median of visual analog scale was 3 for patients in celecoxib group vs 4.5 for
      prednisone group [P<.001]). However, headache frequency and the need for rescue
      medication intake were not different between 2 groups. CONCLUSION: During
      withdrawal in MOH, in order to reduce headache days or rescue medication intake,
      using either of celecoxib or prednisone as a bridge is not different.

PMID- 25600722
TI  - A novel translational animal model of trigeminal autonomic cephalalgias.
AB  - OVERVIEW: Trigeminal autonomic cephalalgias (TACs) are highly disabling primary
      headache disorders that involve severe unilateral head pain coupled with
      significant lateralized cranial autonomic features. Our understanding of these
      disorders and the development of novel and more effective treatments has been
      limited by the lack of a suitable animal model to explore their pathophysiology
      and screen prospective treatments. DISCUSSION: This review details the
      development of a novel preclinical model that demonstrates activation of both the
      trigeminovascular system and parasympathetic projections, thought to be
      responsible for the severe head pain and autonomic symptoms. CONCLUSION: This
      model demonstrates a unique response to TAC specific treatments and highlights
      the importance of the cranial parasympathetic pathway to the pathophysiology of
      TACs and as a potential locus of action for treatments. The development of this
      model opens up opportunities to understand the pathophysiology of these disorders
      further, the likely involvement of the hypothalamus, as well as providing a
      preclinical model with which to screen novel compounds.

PMID- 25600723
TI  - How specific is the translational animal model of trigeminal autonomic
      cephalalgias?

PMID- 25600724
TI  - Lumbar nerve rootlet entrapment by an iatrogenically spliced percutaneous intra
      thecal lumbar cerebrospinal fluid catheter.
AB  - BACKGROUND: Complications associated with the use of percutaneous intra-thecal
      lumbar indwelling spinal catheters include infection, hematoma, neurologic
      dysfunction, and persistent undesired retention among others. A case of
      iatrogenic splicing associated with neurologic dysfunction with the use of a
      percutaneous intra-thecal indwelling spinal catheter is presented in this study.
      METHOD: Single case study review. RESULTS: Review of case materials indicate Y
      pattern splicing/fragmentation of an indwelling intra-thecal catheter causing
      neurologic dysfunction and resistance to removal during attempted removal. Pain
      and weakness were evident soon after insertion of the catheter and were amplified
      with attempted catheter removal. Computed tomography revealed a double dot sign
      on axial view and a Y appearance on sagittal view. Surgical findings revealed
      entrapment of nerve rootlets in the axilla of the spliced catheter. CONCLUSIONS:
      Splicing/fragmentation causing neurologic dysfunction as well as catheter
      retention is described as a potential complication of intra-thecal indwelling
      cerebrospinal fluid catheters. A symptom of fragmentation of a catheter may
      include neurologic dysfunction including pain and weakness of a lumbar nerve
      root. If resistance is experienced upon attempted catheter removal, with or
      without associated neurologic dysfunction, further attempts at removal should not
      be attempted. In those cases in which pain and/or lumbar weakness are evident
      post catheter placement and/or following attempted removal, computed tomography
      should be performed. If fragmentation of a catheter is evident on CT scan, spinal
      surgical consultation should be obtained. Recommended spinal surgical
      intervention includes an open durotomy and visualization of catheter fragments
      and nerve rootlets and removal of catheter fragments.

PMID- 25600725
TI  - Advanced alveolar echinococcosis disease associated with Budd-Chiari syndrome.
AB  - INTRODUCTION: Alveolar echinococceal disease of the liver is rare. Echinococcus
      multilocularis is responsible for the development of the related clinical
      conditions. Advanced disease may result with serious complications such as end
      stage liver disease and Budd-Chiari syndrome. PRESENTATION OF CASE: In this
      presentation, a 28 years-old woman who was a case with advanced alveolar
      echinococcosis complicated with a Budd-Chiari syndrome and was performed
      successful living donor liver transplantation, has been demonstrated with
      clinical and radiological images. DISCUSSION: Initially there may be no clinical
      evidence of the disease in humans for years. Severity and fatality are the
      significant characteristics of the natural history. Extension to the surrounding
      tissues and metastasis of the parasitic mass may be observed. Prevention is
      essential in disease control. Serologic assay may identify the parasite. However,
      early diagnosis is rare. Staging is based on radiologic imaging. Some patients
      with advanced disease may require surgery. Hepatic resection and liver
      transplantation are accepted procedures in selected patients. CONCLUSION: The
      importance of early diagnosis to prevent advanced complications such as
      development of Budd-Chiari syndrome and metastasis has been underlined.

PMID- 25600726
TI  - The complete mitochondrial genome of Jintang black goat (Capra hircus).
AB  - Jintang black goat (Capra hircus) is an indigenous breed of Sichuan province of
      China. It is the first time that the complete mitochondrial genome sequence of
      Jintang black goat is reported in this work, which is determined through the PCR
      based method. The total length of the mitogenome is 16,813 bp, which contains two
      ribosomal RNA genes, 22 tRNA genes, 13 PCGs, and a control region (D-loop
      region). The total base composition of Jintang black goat mitochondrial genome is
      33.52% A, 13.13% G, 27.35% T, and 26.00% C, and in the order A > T > C > G. The
      complete mitochondrial genome of Jintang black goat provides an important data in
      genetic mechanism and the evolution genomes.

PMID- 25600728
TI  - The complete mitochondrial genome of Graphium chironides (Lepidoptera:
      Papilionidae: Papilioninae).
AB  - The complete mitochondrial genome (mitogenome) of Graphium chironides is a
      circular molecule of 15,235 bp in length, containing 37 typical animal
      mitochondrial genes: 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes
      and a non-coding AT-rich region. All PCGs start with a typical ATN initiation
      codon, except for COI, which is initiated with the CGA codon as observed in other
      butterfly species. Eleven PCGs terminate in the complete stop codon TAA or TAG,
      whereas the COI and COII genes end with single T. Twelve intergenic spacers (79
      bp in total) and 15 overlapping regions (42 bp in total) are dispersed throughout
      the whole genome. The two rRNA genes (lrRNA and srRNA) are 1343 bp and 778 bp in
      size, with the AT contents of 84.2% and 85.3%, respectively. All tRNA genes
      display typical secondary cloverleaf structures except for tRNASer(AGN) which
      loses the DHU arm. The 419 bp long AT-rich region contains several features
      common to the other lepidopterans, such as the ATAGA motif followed by a 12 bp
      poly-T stretch, two microsatellite-likes (TA)7 and (TA)9 preceded by the ATTTA
      motif.

PMID- 25600727
TI  - Complete chloroplast genome of the orchid Cattleya crispata
      (Orchidaceae:Laeliinae), a Neotropical rupiculous species.
AB  - A partial genome dataset was sequenced for the orchid Cattleya crispata using
      both Illumina and 454 technologies. The chloroplast genome was assembled using
      iterative runs of MIRA software that yielded a circular molecule with 148,343 bp
      in length and deposited in GenBank database (Accession Number KP168671). The
      plastid genome conserved the quadripartite structure present in most Orchidaceae
      chloroplasts and was composed by 79 protein-coding genes, 39 tRNAs and 8 rRNAs.
      Genome structure, gene order and orientation were similar to previously described
      chloroplasts for Cymbidium orchids, differing in gene order for petN and psbM
      genes. Data described here contain the first report of a complete chloroplast for
      the Neotropical subtribe Laeliinae and may contribute to improve the phylogenetic
      resolution and allow the development of new molecular markers for population
      genetic studies of orchids.

PMID- 25600729
TI  - The complete mitochondrial genome of Shaannan White goat (Capra hircus).
AB  - The Shaannan White goat (Capra hircus), a breed native to China, has the
      characteristics of high fecundity and white fur. In this study, we sequenced the
      complete mitochondrial genome and found its length to be 16,641 bp with the base
      composition of 33.5% A, 26.1% C, 13.1% G and 27.3% T. It has a typical mitogenome
      structure, containing 22 transfer RNA genes, 2 ribosomal RNA genes, 13 protein
      coding genes and a non-coding control region. Most of the genes have ATG
      initiation codons, whereas ND2, ND3 and ND5 genes start with ATA. These results
      provide important reference sequence for future phylogenetic studies.

PMID- 25600730
TI  - The complete mitochondrial genome of Phrynocephalus forsythii (Reptilia,
      Squamata, Agamidae), a toad-headed agama endemic to the Taklamakan Desert.
AB  - The complete mitochondrial genome was sequenced from a viviparous toad-headed
      agama, Phrynocephalus forsythii, which is endemic to the Taklamakan Desert. The
      mitogenome sequence was 17,542 bp in size, containing 13 protein-coding genes, 22
      tRNA genes, two rRNA genes and a control region (D-loop). The gene arrangement
      and composition of P. forsythii is identical to the mitogenome of P. theobaldi in
      that tRNA-Pro was translocated immediately downstream of tRNA-Phe. The D-loop
      comprised two parts, one existing between tRNA-Thr and tRNA-Phe, and another
      containing 12 copies of 36-bp tandem repeats inserting between tRNA-Pro and 12S
      rRNA. The complete mitogenome sequence of P. forsythii may provide fundamental
      data for unveiling the phylogenetic origin and adaptive evolution related to
      Phrynocephalus viviparity.

PMID- 25600731
TI  - The complete mitochondrial genome of the Megalobrama pellegrini (Teleostei:
      Cyprinidae).
AB  - The complete mitochondrial genome of Megalobrama pellegrini was determined by
      using a PCR-based sequencing method. The mitochondrial was 16,620 bp in length,
      including 13 protein genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA
      (tRNA) genes, and one control region. All genes were encoded on the heavy strain
      except for ND6 and eight tRNA genes. The gene arrangement of M. pellegrini was
      similar to those found in the other Megalobrama species. Base composition of the
      heavy strain was A (31.19%), T (24.69%), C (46.37%), G (16.22%) and with A + T
      bias of 55.88%.

PMID- 25600732
TI  - The complete mitochondrial genome of Great tit Parus major (Aves, Passeriformes,
      Paridae).
AB  - The complete mitochondrial genome sequence of Great tit Parus major was sequenced
      used polymerase chain reaction (PCR), long-and-accurate PCR and directly
      sequencing by primer walking. The Genbank accession was KP137624. The entire
      mitochondrial genome of P. major is a circular molecule of 16,776 bp in length
      and the content of A, T, C and G were 29.68%, 22.63%, 33.56% and 14.13%,
      respectively. The complete mitochondrial genome of P. major contains 13 protein
      coding genes, 2 rRNA genes, 22 tRNA genes, plus 1 control regions and was similar
      to most of the other Aves birds in gene arrangement and composition. The complete
      mitochondrial genome of P. major could provide a useful data for resolving
      phylogenetic relationship problems related to Parus and P. major subspecies
      complex.

PMID- 25600733
TI  - The complete mitochondrial genome of Niphotrichum ericoides (Bryophyta,
      Grimmiaceae).
AB  - The mitogenome of Niphotrichum ericoides (GenBank accession number KP 233863) has
      a total length of 106,727 bp and consists of 40 protein-coding genes, three
      ribosomal RNAs (rRNAs), and 24 transfer RNAs. The gene order is identical to that
      known in other moss mitogenomes.

PMID- 25600734
TI  - Complete mitochondrial genome of the Spotted dove (Streptopelia chinensis).
AB  - The Spotted dove (Streptopelia chinensis) is a member of the bird family
      Columbidae. In this study, we report the complete mitochondrial genome of this
      species. The mitochondrial genome of Spotted dove is a circular molecule of
      16,966 bp in size and contains 13 protein-coding genes, two rRNA genes, 22 tRNA
      genes, and one control region. The total base composition is 30.1% for A, 32.1%
      for C, 13.9% for G, and 23.9% for T. These data will be useful for the
      phylogenetic and population diversity analyses of birds, especially Columbidae
      species.

PMID- 25600735
TI  - Complete mitochondrial genome of Triplophysa bleekeri (Cypriniformes:
      Balitoridae: Nemacheilinae), and analysis of mitochondrial genetic variability
      among Triplophysa species.
AB  - The complete mitochondrial genome of the stone loach Triplophysa bleekeri
      collected from the Anning River, a tributary of the Yalong River, in Sichuan
      Province was sequenced. The genome is 16,573 bp in length, consisting of 13
      protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA)
      genes, and a noncoding control region. Most of the genes are encoded on the heavy
      strand, except for ND6 and eight tRNAs. The overall base composition of T.
      bleekeri is 28.1% for A, 28.4% for T, 25.5% for C, 18.0% for G, with a slight A+T
      bias of 56.5%. The complete mitochondrial genetic variability is high among
      different Triplophysa species and between the two T. bleekeri individuals from
      different rivers.

PMID- 25600736
TI  - The complete mitochondrial genome sequence of Thunnus alalunga (Bonnaterre,
      1788).
AB  - Thunnus alalunga is an excellent food fish and is of great importance in
      recreational fisheries. In the study, the complete mitochondrial genome
      (mitogenome) of T. alalunga is sequenced and annotated, which is a circular DNA
      molecule with 16,527 bp in length. The overall nucleotide base composition of T.
      alalunga mitogenome is as follows: A, 28.37%; G, 16.69%; T, 25.46%; and C,
      29.49%, with the A+T content of 53.83%, showing an obvious anti-G bias. The
      entire mitogenome encodes 37 genes in all, comprising 13 protein-coding genes
      (ATP6 and ATP8, COI-III, Cytb, ND1-6 and 4L), 22 transfer RNA genes (tRNAs), and
      two ribosomal RNA genes (12S and 16S rRNAs). The complete mitochondrial genome
      sequence of T. alalunga can provide useful information for the studies on
      molecular systematics, stock evaluation, and conservation genetics of teleost
      fishes.

PMID- 25600737
TI  - Complete mitochondrial genome of the Endangered Narrow Sawfish Anoxypristis
      cuspidata (Rajiformes: Pristidae).
AB  - In this study, we describe the first complete mitochondrial sequence for the
      Endangered Narrow Sawfish Anoxypristis cuspidata. It is 17,243 bp in length and
      contains 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and a control
      region with the common vertebrate mitogenomic organization. A total of 30 bp
      overlaps and 28 bp short intergenic spaces are located between all genes. The
      overall base composition is 32.7% A, 25.7% C, 12.9% G, and 28.6% T. Two start
      codons (ATG and GTG) and two stop codons (TAG and TAA/T) were used in all protein
      coding genes. The origin of L-strand replication (OL) sequence (38 bp) formed a
      hairpin structure (13 bp stem and 12 bp loop) to initiate the replication of L
      strand.

PMID- 25600738
TI  - Complete mitochondrial genome of the Asian pencil halfbeak Hyporhamphus
      intermedius (Beloniformes, Hemirhamphidae).
AB  - The complete mitochondrial genome of Hyporhamphus intermedius was determined to
      be 16,720 bp in length with (A + T) content of 56.3%, and it consists of 13
      protein-coding genes, 22 tRNAs, two ribosomal RNAs, and a control region. The
      gene composition and the structural arrangement of the H. intermedius complete
      mtDNA were identical to most of the other vertebrates. Interestingly, two tandem
      repeat units were identified across tRNA-Pro and control region (2*41 bp), while
      in most of the fishes the tandem repeat units are located in the control region.
      The molecular data we presented here could play a useful role to study the
      evolutionary relationships and population genetics of Hemirhamphidae fish.

PMID- 25600739
TI  - The complete mitochondrial genome of the Chrysoperla sinica (Tjeder).
AB  - The complete mitochondrial genome of the Chrysoperla sinica was sequenced in this
      study. It is 16,057 bp in length, and contains 22 transfer RNA genes, 13 protein
      coding genes (PCGs), 2 rRNA genes and 1 non-coding AT-rich region. But, C. sinica
      lack long tandem repeats. The Chrysoperla sinica mitogenome displays a very high
      level of similarity (99.27%) with Chrysoperla nipponensis. The genome base
      composition is 39.24% A, 39.70% T, 11.98% C, and 9.08% G. Similar to other
      insects, all PCGs are initiated by a typical ATN codon, except COX1, which starts
      with TCG. Nine PCGs have the standard, complete stop codon (TAA or TAG), and the
      other four PCGs end with the incomplete stop codon (TA or T).

PMID- 25600740
TI  - The complete mitogenome of the minute mudskipper, Periophthalmus minutus Eggert,
      1935 (Perciformes: Gobiidae: Oxudercinae).
AB  - The mitogenome of an Australian sample of the mudskipper, Periophthalmus minutus,
      was recovered from partial sequencing using the MiSeq sequencer. This mudskipper
      has a mitogenome of 16,506 base pairs (55% A + T content) made up of two
      ribosomal subunit genes, 13 protein-coding genes, 22 transfer RNAs, and a 838 bp
      non-coding AT-rich region. This is the first sequenced mitogenome for the genus
      Periophthalmus and the fifth for the subfamily Oxudercinae.

PMID- 25600741
TI  - The complete sequence of the mitochondrial genome of Liangshan pig (Sus Scrofa).
AB  - Liangshan pig is one of the famous native breeds in Sichuan province in China. It
      lives in the mountainous areas (about 1500-2500 m altitude) and has a superior
      meat quality. Here, the complete mitochondrial genome sequence of Liangshan pig
      was first reported. The total length of mitochondrial genome is 16,760 bp,
      including 34.62% A, 25.79% T, 26.20%, C and 13.39% G, with an A + T bias of
      60.41%. Mitochondrial genome contains a major non-coding control region (D-Loop
      region), two ribosomal RNA genes, 13 protein-coding genes (PCGs), and 22 transfer
      RNA genes. The D-loop region is located between the tRNA-Pro and tRNA-Phe genes
      with a length of 1324 bp, some tandem repeat sequences was found in the region.
      The mitochondrial genome of Liangshan pig provides an important role in genetic
      mechanism.

PMID- 25600742
TI  - The complete mitochondrial genome of the hybrid grouper Epinephelus coioides? *
      Epinephelus lanceolatus?.
AB  - The complete mitochondrial genome of the hybrid grouper (Epinephelus coioides? *
      Epinephelus lanceolatus?) was presented in this study. The mitochondrial genome
      is 16,743 bp long and consists of 13 protein-coding genes, two rRNA genes, 22
      tRNA genes, and a control region. The gene order and the composition of the
      hybrid grouper mitochondrial genome were similar to that of most other
      vertebrates. The nucleotide compositions of the light strand are 26.56% of A,
      15.79% of C, 28.74% of T, and 28.91% of G. With the exception of the NADH
      dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes
      are encoded on the heavy strand.

PMID- 25600743
TI  - Complete mitochondrial genome sequence and mutations of the lung carcinoma model
      inbred C57BL/6 mice strain.
AB  - In the present work, we undertook the complete mitochondrial genome sequencing of
      an important lung carcinoma model inbred rat strain for the first time. The total
      length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two
      ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region (D
      loop region). The mutation events were also reported.

PMID- 25600744
TI  - The complete mitochondrial genome of Parnassius cephalus (Lepidoptera:
      Papilionidae: Parnassinae).
AB  - The complete mitochondrial genome of Parnassius cephalus is 15,343 bp in length,
      containing 13 protein-coding genes (PCGs), 22 tRNA genes, 2 ribosomal RNA genes
      and a noncoding AT-rich region. All the 13 PCGs are initiated with the codon ATN,
      except for COI gene which starts with codon CGA. Eleven PCGs stop with the
      termination codon TAN, while the COI and COII genes end with single nucleotide T.
      All the tRNA genes have the typical secondary clover-leaf structures except
      tRNASer (AGN), which loses its DHU stem. The two rRNA genes (lrRNA and srRNA) are
      1341 bp and 777 bp in length, with their AT contents being 83.75% and 85.33%,
      respectively. The AT-rich region is 487 bp in length, and contains some
      conservative structures similar to other butterfly mitogenomes, such as a 17 bp
      poly-T stretch preceded by the ATAGA motif, and a microsatellite-like (AT)10
      element preceded by the ATTTA motif.

PMID- 25600745
TI  - The complete mitochondrial genome of large flying fox, Pteropus vampyrus
      (Pteropus, Pteropodidae).
AB  - The large flying fox (Pteropus vampyrus) is named after its fox-like face and
      noted for being one of the largest bats. Here, we reported the complete
      mitogenome sequence of P. vampyrus, which was 16,554 bp and composed of 13
      protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region, with
      a base composition of lower G+C content (41.5%). Like other bats, all genes were
      located on H-strand except for eight tRNA and ND6 genes. Most protein-coding
      genes started with an ATG codon except for ND2, ND3, and ND5, which initiated
      with ATA or ATT instead, and terminated with the typical stop codon (TAA/TAG) or
      a single T or an unexpected codon of AGG. Within the control region, 6 bp repeat
      (TACGCA) was appeared only nine times, much lower than other published Pteropus
      species. These results provided basic information for researching Pteropus
      vampyrus on genetics, phylogeny, and adaptive evolution.

PMID- 25600746
TI  - Complete mitochondrial genome sequence and mutations of the Lung cancer model
      inbred athymic Rowett nude rat strain.
AB  - In the present work, we undertook the complete mitochondrial genome sequencing of
      an important Lung cancer model inbred rat strain for the first time. The total
      length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two
      ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region (D
      loop region). The mutation events were also reported.

PMID- 25600747
TI  - Next generation sequencing yields the complete mitochondrial genome of the
      Clarion angelfish, Holacanthus clarionensis (Perciformes: Pomacanthidae).
AB  - In this study, the complete mitogenome sequence of the Clarion angelfish,
      Holacanthus clarionensis (Perciformes: Pomacanthidae) has been sequenced by next
      generation sequencing method. The length of the assembled mitogenome is 16,615
      bp, including 13 protein coding genes, 22 transfer RNAs, and two ribosomal RNAs
      genes. The overall base composition of Clarion angelfish is 28.3% for A, 29.3%
      for C, 16.5% for G, 25.9% for T and show 85% identities to flame angelfish
      Centropyge loriculus. The complete mitogenome of the Clarion angelfish provides
      essential and important DNA molecular data for further phylogeography and
      evolutionary analysis for marine angelfish phylogeny.

PMID- 25600748
TI  - The complete mitochondrial genome of Pseudopodoces humilis (Passeriformes,
      Paridae).
AB  - The complete sequence of Pseudopodoces humilis mitochondrial genome was
      determined by using L-PCR and conserved primer walking approaches. The results
      showed that the entire mitochondrial genome of P. humilis was 16,758 bp in length
      with 52.5% A + T content; the genome harbored the same gene order with that of
      other birds, including 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes and 1
      non-coding control region. All tRNAs formed typical cloverleaf secondary
      structures (excluding tRNASer-AGN). The control region (D-loop) of P. humilis was
      located between tRNAGlu and tRNAPhe with 1168 bp length, no repetitive sequence.

PMID- 25600749
TI  - Next generation sequencing yields the complete mitochondrial genome of the
      Japanese angelfish, Centropyge interrupta (Perciformes: Pomacanthidae).
AB  - In this study, the complete mitogenome sequence of the Japanese angelfish,
      Centropyge interrupta (Perciformes: Pomacanthidae), has been sequenced by the
      next-generation sequencing method. The assembled mitogenome consisting of 16,595
      bp includes 13 protein coding genes, 22 transfer RNAs, and two ribosomal RNAs
      genes. The overall base composition of Japanese angelfish is 27.5% for A, 29.3%
      for C, 17.3% for G, 25.9% for T, and shows 85% identities to flame angelfish
      Centropyge loriculus. The complete mitogenome of the Japanese angelfish provides
      essential and important DNA molecular data for further phylogeography and
      evolutionary analysis for marine angelfish phylogeny.

PMID- 25600750
TI  - The complete mitochondrial genome of Bombyx mori strain Jin6 (Lepidoptera:
      Bombycidae).
AB  - In this study, the complete mitochondrial genome of Bombyx mori strain Jin6
      (Lepidoptera: Bombycidae) has been reported for the first time. It was a circular
      molecule of 15,648 bp in length, containing 37 typical coding genes and one non
      coding AT-rich region. The overall composition of the mitogenome was A (43.05%),
      G (7.30%), C (11.35%), and T (38.29%). Its gene order and content were identical
      to the common type found in most insect mitogenomes. All protein coding genes
      (PCGs) started with a typical ATN initiation codon, except for the cox1 gene,
      which began with CGA codon. Eleven genes used standard complete termination codon
      TAA, whereas the cox1 and cox2 genes ended with single T. All tRNA genes
      displayed typical secondary cloverleaf structures as those of other insects.
      Additionally, the 494 bp long AT-rich region contained several structures common
      to the other lepidopterons, such as some structures of repeated motifs and
      microsatellite-like elements.

PMID- 25600751
TI  - The complete mitochondrial genome of a deep-water Baikalian amphipoda
      Brachyuropus grewingkii (Dybowsky, 1874).
AB  - In this study, we present a complete mitochondrial genome of a deep-water
      amphipoda Brachyuropus grewingkii (Dybowsky, 1874) from Lake Baikal. A circular
      mitochondrial DNA has 17,118 bp in length and contains 13 protein-coding genes,
      two ribosomal RNA genes, 22 transfer RNA genes, a putative control region, and
      five intergenic spacers. An extended control region and altered positions of some
      tRNA genes distinguish mitochondrial genome of B. grewingkii from the
      mitochondrial genomes described for other Baikalian amphipoda species.

PMID- 25600752
TI  - The complete mitochondrial genome of the black-tailed brush lizard Urosaurus
      nigricaudus (Reptilia, Squamata, Phrynosomatidae).
AB  - Previous studies using mitochondrial DNA (mtDNA) genes suggest the black-tailed
      brush lizard, Urosaurus nigricaudus, which is a small-sized lizard from the
      peninsula of Baja California, Mexico, has 4 deeply isolated mtDNA lineages with
      sequence divergence ranging from 4% to 11.2%. We present its complete
      mitochondrial genome. This genome is 17,298 bp long and comprises 2 rRNAs, 22
      tRNAs, 13 protein-coding genes, 1 L-strand origin of replication and 1 control
      region. The overall nucleotide content is A = 34.2%; C = 26.8%; G = 13.5%; T =
      25.5%. The gene organization and features agree with the general vertebrate
      organization and that found in other lizards. The control region is 1909 bp long
      and is located between tRNAPro and tRNAPhe.

PMID- 25600753
TI  - Hippocampal orexin receptors inactivation reduces PTZ induced seizures of male
      rats.
AB  - INTRODUCTION: Orexin has been shown to be involved in a number of physiological
      and behavioral processes including, feeding and metabolism, reward, nociception,
      and anxiety. Furthermore, orexin can cause increased neuronal excitability that
      gives rise to epileptic activity. The distribution of orexin receptor expression
      in the hippocampus, suggests a possible importance of orexin in the control of
      seizures in the temporal lobe epilepsy. Therefore, in this study, the effect of
      hippocampal orexin 1 and 2 receptors on seizure and glutamate and GABA (gamma
      aminobutyric acid) contents was explored. MATERIALS AND METHODS: Orexin 1
      receptor (OX1R) antagonist (SB) and OX2R antagonist (TCS) were administrated
      bilaterally through separate cannulae into both hippocampi. Behavioral
      convulsions were provoked by intravenous pentylenetetrazol (PTZ) application
      model. The amount of total hippocampal glutamate and GABA contents was then
      measured by a biochemical method. RESULTS: SB (50 nmol) infusion reduced seizure
      stage, duration and decreased glutamate while GABA content was increased. SB (200
      nmol) also reduced seizure stage, duration and glutamate content, without change
      of GABA content. TCS (20 nmol) infusion reduced seizure stage and duration
      without concomitant change in glutamate and GABA contents. Further, TCS (40 nmol)
      did neither affect the seizure nor the GABA, while decreased glutamate content.
      Co-administration of SB (50 nmol) with TCS (40 nmol) and also SB (200 nmol) with
      TCS (40 nmol) reduced seizure stage, duration and glutamate, but increased GABA
      content. CONCLUSION: It is concluded that OX1R and OX2R antagonists reduce
      convulsive intensity, partially through alterations of hippocampal glutamate and
      GABA contents.

PMID- 25600755
TI  - A sudden flare-up of a quiescent oral lichen planus: methylisothiazolinone as the
      prime suspect?

PMID- 25600754
TI  - Early-life risperidone administration alters maternal-offspring interactions and
      juvenile play fighting.
AB  - Risperidone is an antipsychotic drug that is approved for use in childhood
      psychiatric disorders such as autism. One concern regarding the use of this drug
      in pediatric populations is that it may interfere with social interactions that
      serve to nurture brain development. This study used rats to assess the impact of
      risperidone administration on maternal-offspring interactions and juvenile play
      fighting between cage mates. Mixed-sex litters received daily subcutaneous
      injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days
      (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In
      observations made between PNDs 14-17, risperidone significantly suppressed
      several aspects of maternal-offspring interactions at 1-hour post-injection. At
      23 h post-injection, pups administered risperidone had lower activity scores and
      made fewer non-nursing contacts with their moms. In observations of play-fighting
      behavior made once a week between PNDs 22-42, risperidone profoundly decreased
      many forms of social interaction at 1h post-injection. At 23h post-injection,
      rats administered risperidone made more non-social contacts with their cage
      mates, but engaged in less social grooming. Risperidone administration to rats at
      ages analogous to early childhood through adolescence in humans produces a
      pattern of abnormal social interactions across the day that could impact how such
      interactions influence brain development.

PMID- 25600756
TI  - Robot-assisted laparoscopic partial nephrectomy in patients with previous
      abdominal surgery: single center experience.
AB  - BACKGROUND: The aim of this study is to report our single center experience with
      robotic partial nephrectomy (RPN) in patients with history of previous abdominal
      surgery (PAS). METHODS: Medical records of patients who underwent RPN for a
      single renal mass in our center from 2006 to 2013 were reviewed. Patients were
      divided in two groups: those who had history of PAS and those without history of
      PAS. Within the PAS group, four sub-groups were considered: (a) remote site of
      PAS in relation to RPN; (b) PAS in the proximity of RPN site; (c) previous
      umbilical hernia/abdominal hernia mesh repair; (d) major PAS. RESULTS: In total
      627 patients were analyzed, and of these 321 patients had history of PAS (51.2%).
      On univariable and multivariable analyses, only Charlson Comorbidity Index,
      estimated blood loss, and tumor size were the significant predictors of
      complications. CONCLUSIONS: RPN can be safely performed in patients with history
      of PAS with surgical outcomes comparable with those obtained in patients without
      history of PAS.

PMID- 25600757
TI  - Direct evidence for a substantive reaction between the Criegee intermediate,
      CH2OO, and the water vapour dimer.
AB  - The C1 Criegee intermediate, CH2OO, reaction with water vapour has been studied.
      The removal rate constant shows a quadratic dependence on [H2O], implying
      reaction with the water dimer, (H2O)2. The rate constant, kCH2OO+(H2O)2 = (4.0 +/
      1.2) * 10(-12) cm(3) molecule(-1) s(-1), is such that this is the major
      atmospheric sink for CH2OO. 

PMID- 25600758
TI  - A retrospective audit of skin biopsies done in a tertiary care center in India.
AB  - BACKGROUND: Skin biopsies are an invaluable tool in the diagnostic armamentarium
      of a dermatologist and have several factors that determine outcome. OBJECTIVES:
      The aim of this study was to retrospectively assess the quality of data included
      in the pathology request forms and reports and to assess the level of
      clinicopathological correlation in the reported biopsy specimens. METHODS: We
      retrospectively analyzed 3006 histopathology request forms and reports of skin,
      mucosal, and nail biopsies to assess the quality of data included in them and
      assessed the level of clinicopathological correlation in these biopsies. Two
      hundred discordant histopathology slides were randomly reviewed by a pathologist
      in the presence of a dermatologist to analyze the causes for discordance.
      RESULTS: The pathological diagnosis was concordant with clinical diagnosis in
      1798 (59.8%) biopsies, partially concordant in 228 (7.6%) biopsies, and
      discordant in 929 (30.9%) biopsies. In a clinicopathologically concordant
      category, the duration for reporting the biopsies was significantly shorter, and
      the definitive pathologist's diagnosis was frequently mentioned. Of the 200
      discordant slides reviewed randomly by a pathologist in the presence of a
      dermatologist, 7.5% slides afterward turned out to be consistent and 15%
      partially consistent with the diseases in doubt. CONCLUSION: Several deficits
      were identified that need to be rectified to improve the diagnostic accuracy of
      skin biopsy. A portion of discordant slides showing features compatible with the
      disease when reviewed by a pathologist and dermatologist together emphasizes the
      importance of a joint review by both in doubtful cases.

PMID- 25600759
TI  - Gene expression signatures as a therapeutic target for severe H7N9 influenza -
      what do we know so far?
AB  - A novel H7N9 avian influenza A virus (IAV) emerged in China in early 2013 causing
      > 450 cases of respiratory illness and 175 deaths within a 20-month period.
      Though avian viruses infect humans infrequently, the lack of human immunity to
      these viruses raises the possibility of a pandemic if they were to acquire the
      ability to transmit efficiently. Despite the fact that IAV pathogenicity results
      from the cytopathic effects and tissue damage caused by both viral replication
      and an overly robust immune response, current IAV therapeutics only target the
      viral proteins. This has led to the emergence of drug resistance due to the high
      mutation rates of viruses. The growing obsolescence of our current influenza
      therapeutics underscores the need for alternative treatment strategies. One
      promising area of research is the use of drugs that target the host response to
      IAV infection. This article describes how gene expression profiling can be used
      to predict drugs that reverse the destructive effects of the host response to
      H7N9 and other pathogenic influenza viruses. 

PMID- 25600760
TI  - Effect of perioperative blood transfusion on mortality for major urologic
      malignancies.
AB  - INTRODUCTION: Patients who undergo surgical treatment for malignancy often
      receive perioperative blood transfusion (PBT). We examined the association
      between PBT and mortality in patients who received surgical treatment of
      prostate, bladder, and kidney cancer. MATERIALS AND METHODS: Using the
      Surveillance, Epidemiology, and End Results-Medicare data set from 1992-2009, we
      identified 28,854 men with prostate cancer, 5462 patients with bladder cancer,
      and 14,379 patients with renal cell carcinoma who underwent radical prostatectomy
      (RP), radical cystectomy (RC), or radical (RN) or partial nephrectomy (PN) as
      primary therapy. Univariate and multivariate models were used to evaluate the
      association of PBT with cancer-specific mortality (CSM) and all-cause mortality
      (ACM). RESULTS: The rate of PBT in bladder and kidney cancer have been increasing
      over time, and PBT in prostate cancer steadily increased and peaked in 2002 and
      declined afterward. The median follow-up for the RP, RC, and RN/PN cohorts were
      70 months, 21 months, and 39 months, respectively. In the RP cohort, PBT was
      associated with greater CSM (hazard ratio [HR], 1.609; 95% confidence interval
      [CI], 1.235-2.097; P = .0004) and ACM (HR, 1.121; 95% CI, 1.006-1.251; P =
      .0394). In the RC cohort, PBT was not associated with greater CSM (HR, 1.047; 95%
      CI, 0.917-1.195; P = .4962) or ACM (HR, 1.095; 95% CI, 0.998-1.200; P = .0547).
      In the nephrectomy cohort, PBT was associated with greater CSM (HR, 1.365; 95%
      CI, 1.167-1.597; P = .0001) and ACM (HR, 1.402; 1.273-1.544; P < .0001).
      CONCLUSION: PBT was associated with increased CSM and ACM for prostate and kidney
      cancer in a multivariate model. Although these data do not identify a causative
      relationship between PBT and mortality, efforts made to limit PBT in patients who
      undergo urologic cancer surgery can yield long-term survival benefits.

PMID- 25600762
TI  - Impact of small changes in particle surface chemistry for unentangled polymer
      nanocomposites.
AB  - We report microstructural and rheological consequences of altering silica
      particle surface chemistry when the particles are suspended in unentangled
      polyethylene glycol with a molecular weight of 400. The particle surfaces are
      altered by reacting them with isobutyltrimethyoxysilane. Levels of silanization
      are chosen so that the particles remain dispersed in the polymer at all volume
      fractions studied. Our studies indicate that at the levels studied, silanization
      does not alter the hydrodynamic thickness of the absorbed polymer layer
      thickness. Rheological properties are not sensitive to levels of silanization up
      to particle volume fractions where the average particle separation h ~ 6Rg (4.8
      nm). At these volume fractions, composite microstructure undergoes changes
      associated with jamming of soft particles (decorrelations in the first peak of
      the particle structure factor and the onset of a non-diffusive mechanism that
      dominates particle density fluctuations at short times.) In the region of volume
      fractions where h/Rg < 6, the zero-shear rate viscosity of the composites is
      extremely sensitive to level of silanization with a decrease in the zero-shear
      rate viscosity by four orders of magnitude observed for the highest levels of
      silanization studied in comparison to the bare particles. 

PMID- 25600761
TI  - Treatment With Galeterone in an Elderly Man With Castration-Resistant Prostate
      Cancer: A Case Report.

PMID- 25600763
TI  - Kienbock's disease.
AB  - The pathophysiology of Kienbock's disease is not well understood: factors that
      were previously considered as potentially being responsible for the disease are
      now only seen as predisposing factors that contribute to discovering pre-existing
      disease. The natural history of the disease is also not well known. The
      arthroscopic classification proposed by Bain and Begg is now an essential
      supplement to the well-known Lichtman radiographic classification system. Various
      treatment options exist and some are better suited to each stage of the disease.
      This review will explore the advantages and disadvantages of these treatment
      options and match them with the best indications. 

PMID- 25600764
TI  - The ratio of early transmitral flow velocity (E) to early mitral annular velocity
      (Em) predicts improvement in left ventricular systolic and diastolic function 1
      year after catheter ablation for atrial fibrillation.
AB  - AIMS: Successful rhythm control after atrial fibrillation catheter ablation is
      known to induce left atrial reverse remodelling and improve left ventricular (LV)
      function. We explored the clinical factors affecting LV systolic and diastolic
      function 1-year after catheter ablation for atrial fibrillation. METHODS AND
      RESULTS: We compared pre-procedural and 1-year follow-up echocardiograms in 521
      patients with atrial fibrillation who underwent catheter ablation. Left
      ventricular systolic function was estimated by the ejection fraction (EF);
      diastolic function was estimated by the ratio of early transmitral flow velocity
      (E) to early mitral annular velocity (Em). (i) Catheter ablation of atrial
      fibrillation significantly reduced left atrium volume index (P < 0.001) and
      improved LV EF both in patients with recurrent atrial fibrillation (n = 133, P =
      0.008) and those without recurrence (n = 388, P < 0.001). (ii) Follow-up EF was
      significantly improved in patients with baseline E/Em < 15 (n = 454, P < 0.001),
      whereas E/Em was significantly reduced in patients with pre-procedural E/Em >= 15
      (n = 67, P = 0.008). (iii) Baseline E/Em < 15 (beta = -3.854, 95% CI -5.99 to 
      1.72, P < 0.001), baseline EF <50% (beta = 10.586, 95% CI 7.55 to 13.63, P <
      0.001), and female (beta = -1.726, 95% CI -3.36 to -0.10, P = 0.038) were
      independently associated with improved EF. Baseline E/Em >= 15 (beta = 4.896, 95%
      CI 3.45 to 6.34, P < 0.001) and younger age (beta = -0.066, 95% CI -0.11 to 
      0.02, P = 0.003) were independent factors associated with improved E/Em.
      CONCLUSION: Pre-procedural E/Em predicted improvement in LV systolic and
      diastolic functions 1 year after catheter ablation for atrial fibrillation. Low
      baseline E/Em was independently associated with improved EF, while high E/Em
      predicted improvement in LV diastolic function.

PMID- 25600766
TI  - Examination of the differential impacts of antitachycardia pacing vs. shock on
      patient activity in the EMPIRIC study.
AB  - AIMS: Implantable cardioverter defibrillators (ICDs) have demonstrated mortality
      advantages over antiarrhythmic drug therapy, but ICD shock has known detrimental
      effects on quality of life and psychologic functioning. However, it remains
      unknown how patient activity level is affected by shock, or by antitachycardia
      pacing (ATP), which was developed to reduce the treatment burden of shocks.
      Examine the differential impact of ICD shock and ATP on patient activity level as
      a novel way to capture the relative behavioural repercussions of these ICD
      therapies. METHODS AND RESULTS: Accelerometer-derived activity data were analysed
      for a subset of patients (males = 83%; mean age = 62 years) enrolled in the
      EMPIRIC trial who received shock (n = 71) or ATP (n = 103). Differences in
      activity between a week pre-therapy and a week post-therapy were examined to
      assess the behavioural repercussions of shock vs. ATP when one, few (2-4), or
      many (5+) therapies were delivered. For patients receiving shock, a significant
      reduction in activity was observed for few (-26%) and many shocks (-34%) in the
      first week post-therapy (P < 0.05). In weeks 2-4, activity levels recovered
      towards baseline levels. In contrast, no level of ATP-only therapy significantly
      reduced patients' activity levels at any time following therapy. CONCLUSION: This
      study is the first to evaluate objective, behavioural effects of shock, and
      whether these effects are comparable with ATP therapy alone. In tandem with
      existing literature, current results highlight that ICD shocks and ATP have
      divergent effects on behavioural outcomes, with ATP's effect profile in these
      domains appearing somewhat favourable.

PMID- 25600765
TI  - Differential diagnosis of wide QRS tachycardias: comparison of two
      electrocardiographic algorithms.
AB  - AIMS: This study's aim is to compare the ability of two ECG criteria to
      differentiate ventricular (VT) from supraventricular tachycardia (SVT): Brugada
      et al. [horizontal plane (HP) leads] and Vereckei et al. [frontal plane (FP),
      specifically aVR lead], having electrophysiological study (EPS) as gold standard.
      After comparing, suggestions for better diagnosis of wide QRS-complex tachycardia
      (WCT) in emergency situations were made. METHODS AND RESULTS: Fifty-one
      consecutive patients with 12-lead ECG registered during EPS-induced regular WCT
      were selected. Each ECG was split into two parts: HP (V1-V6) and FP (D1-D3, aVR,
      aVL, and aVF), randomly distributed to three observers, blinded for EPS diagnosis
      and complementary ECG plane, resulting in total 306 ECG analyses. Observers
      followed the four steps of both algorithms, counting time-to-diagnosis. Global
      sensitivity, specificity, percentage of incorrect diagnoses, and step-by-step
      positive/negative likelihood ratios (+LR and -LR) were calculated. Kaplan-Meier
      curve was plotted for final time-to-diagnosis. Inter-observer agreement was
      assessed with kappa-statistic. Global sensitivity was similarly high in FP and HP
      algorithms (89.2 vs. 90.1%), and incorrect classifications were 27.4 vs. 24.7%.
      Forty-eight correct analyses by Vereckei criteria took 9.13 s to diagnose VT in
      the first step, showing that first step was fast, with high +LR, generating
      nearly conclusive pre- (72.6%) to post-test (98.0%) changes for VT probability.
      CONCLUSION: Both algorithms as a whole are similar for diagnosis of WTC; however,
      the first step of Vereckei (initial R in aVR) is a simple, reproducible,
      accurate, and fast tool to use. The negativity of this step requires a 'holistic'
      approach to distinguish VT from SVT.

PMID- 25600767
TI  - Long-term results of surgical minimally invasive pulmonary vein isolation for
      paroxysmal lone atrial fibrillation.
AB  - AIMS: Transcatheter pulmonary vein ablation is the current treatment of choice
      for symptomatic drug-refractory atrial fibrillation (AF). Video-assisted surgical
      pulmonary vein isolation (sPVI) is an alternative therapy to percutaneous
      ablation for the treatment of AF. Long-term results of sPVI are currently
      unknown. The aim of this study was to report on the long-term efficacy and safety
      of sPVI in patients with paroxysmal AF. METHODS AND RESULTS: The study design was
      observational and retrospective. From July 2005 to January 2011, 42 patients with
      drug-refractory paroxysmal AF underwent video-assisted sPVI in two different
      centres. Patients were eligible for sPVI when suffering from symptomatic, drug
      refractory paroxysmal AF and they agreed to the alternative of sPVI. The median
      preoperative AF duration was 24 months (range 3-200). Success was defined as the
      absence of AF on 24 h or 96 h Holter monitoring during follow-up, off
      antiarrhythmic drugs (AAD). Adverse events and follow-up monitoring were based on
      the Heart Rhythm Society Consensus Statement 2012 for the catheter and surgical
      ablation of AF. Mean age was 55 +/- 10 years, and 76% were males. After a mean
      follow-up of 5 years (SD 1.7), 69% of all patients were free from atrial
      arrhythmias without the use of AAD, and 83% with the use of AAD. Major peri
      procedural adverse events occurred in four (9.5%) patients, no strokes or
      mortalities were registered during long-term follow-up. CONCLUSION: This
      retrospective study shows that sPVI for the treatment of paroxysmal AF is
      effective and that the outcomes are maintained at long-term follow-up.

PMID- 25600768
TI  - Invasive electrophysiological evaluation and ablation in patients with
      asymptomatic ventricular pre-excitation persistent at exercise stress test.
AB  - AIMS: In patients with asymptomatic ventricular pre-excitation (VPE) persistent
      at exercise stress test, this study evaluates the proportion of cases with
      adverse conduction properties of the atrioventricular accessory pathway (AP) at
      invasive electrophysiological study and the long-term follow-up after they
      received treatment according to pre-determined criteria. METHODS AND RESULTS:
      Over 10 years, asymptomatic patients with VPE persistent at exercise stress test
      referred for invasive electrophysiological evaluation including isoproterenol
      (IPN) infusion were included. Ablation was planned if they had at least one of
      the following criteria: (i) shortest pre-excited R-R interval (SPERRI) <=250 ms
      and/or (ii) inducible atrioventricular re-entrant tachycardia (AVRT).
      Cryoablation was electively used in para-hisian and mid-septal APs. Patients non
      eligible for ablation received no therapy. Sixty-three patients (45 males; mean
      age 26 +/- 14 years) underwent electrophysiological evaluation: 7 had fasciculo
      ventricular fibres and were excluded, whereas 56 had 58 APs. Thirty-one patients
      (55%) were eligible and underwent successful ablation: 87% had at least the
      SPERRI <= 250 ms and 61% had at least inducible AVRT. In 15 cases (48%) the
      ablation criteria were met only during IPN infusion. During follow-up (73 +/- 33
      months), one patient was successfully retreated for resumption of VPE in the
      ablation group, whereas no event was observed in the group of patients who
      received no treatment. CONCLUSION: In this subset of patients with asymptomatic
      VPE, invasive electrophysiological evaluation shows fast antegrade conduction
      over the AP and/or inducible AVRT in about half of the cases. Patients who
      received no therapy because of a benign electrophysiological profile had an event
      free follow-up.

PMID- 25600769
TI  - A novel ent-kaurane diterpenoid executes antitumor function in colorectal cancer
      cells by inhibiting Wnt/beta-catenin signaling.
AB  - Aberrant activation of Wnt signaling pathway is crucial for the onset and
      progression of human colorectal cancer (CRC). Owing to the persistent dependence
      on Wnt signaling for growth and survival, inhibition of this pathway is an
      attractive approach for new therapies. 11alpha, 12alpha-epoxyleukamenin E (EPLE)
      is a novel ent-kaurane diterpenoid that we previously isolated from Salvia
      cavaleriei, exhibiting antitumor activities in a variety of cancer cells. Herein,
      we found that whereas sparing normal human colon mucosal epithelial cells, EPLE
      selectively inhibited the proliferation of CRC cell lines as well as primary
      tumor cells. Mechanistically, we demonstrated EPLE exerted its function through
      suppressing Wnt signaling pathway, as evidenced by EPLE-mediated downregulation
      of Wnt target genes such as c-Myc, Axin2 and Survivin. Consistently, luciferase
      reporter assays showed that the EPLE directly blocked Wnt/beta-catenin-mediated
      transcriptional activation. In combination of co-immunoprecipitation and protein
      structure-based analyses, we determined that the EPLE entered the interface of
      beta-catenin/TCF4 complexes and blocked their interaction that is required for
      beta-catenin-mediated transcriptional activation. Moreover, overexpression of
      beta-catenin alleviated the cytotoxicity of EPLE in CRC cells, supporting Wnt
      signaling is a major and specific target of EPLE. Combined treatments of EPLE and
      5-fluorouracil, the first-line chemotherapy for CRC patients, achieved a
      synergistic effect. More importantly, EPLE hampered tumor development in a CRC
      xenograft model. Our data thus establish EPLE as a novel inhibitor of Wnt
      signaling that holds great promise as a potential candidate for further
      preclinical evaluation for CRC treatments. 

PMID- 25600770
TI  - Twist1 and AP-1 cooperatively upregulate integrin alpha5 expression to induce
      invasion and the epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is an important process implicated in
      tumor invasion and metastasis. Twist1 is a transcription factor that induces EMT,
      including E-cadherin suppression and cancer cell migration and invasion; hence it
      promotes cancer metastasis. Twist1 directly or indirectly regulates the
      expression of various genes and cellular functions involved in cancer
      progression. However, the underlying mechanisms remain largely unknown. In this
      study, we investigated the molecular basis for Twist1-mediated invasion and EMT.
      In human cancer cells, Twist1 was found to directly upregulate transcription of
      the mesenchymal gene integrin alpha5 in an E-box-independent, but activating
      protein-1 (AP-1) element-dependent, manner. Twist1 activated the integrin alpha5
      promoter by interacting with and activating the transcription factor AP-1,
      composed of c-Jun and activating transcription factor-2 (ATF-2); it also enhanced
      the nuclear presence of ATF-2. AP-1 was critical for Twist1-induced cancer cell
      invasion, primarily through the induction of integrin alpha5, which activated c
      Jun N-terminal kinase and focal adhesion kinase-signaling activities. Using data
      from The Cancer Genome Atlas, we found that Twist1 expression positively
      correlates with integrin alpha5 expression in human colorectal cancers. These
      findings suggest that cooperation between Twist1 and AP-1 represents a novel
      mechanism for EMT and tumor invasiveness. This study supports further
      investigation into the molecular basis underlying the diverse Twist1-mediated
      functions that occur during tumor progression. 

PMID- 25600771
TI  - Hepatitis B immunity in Australia: a comparison of national and prisoner
      population serosurveys.
AB  - In Australia, hepatitis B (HBV) vaccination is recommended for injecting drug
      users (IDUs), Indigenous adults and prisoners. We compared immunity to HBV in
      prisoners and the general population obtained from national serosurveys in 2007.
      Individuals with HBV surface antibody (HBsAb) positive sera were considered
      immune from past infection [HBV core antibody (HBcAb) positive] or from
      vaccination (HBcAb negative). Male prisoners aged 18-58 years had a higher HBsAb
      seroprevalence than the general population (46.4% vs. 39.4%, P = 0.061).
      Comparison of HBcAb results was possible for males aged 18-29 years. In this
      group, higher HBsAb seroprevalence was due to past infection (12.9% vs. 3.0%, P <
      0.001), rather than vaccine-conferred immunity (35.3% vs. 43.4%, P = 0.097). All
      prisoner groups, but especially IDUs, those of Indigenous heritage or those with
      a previous episode of imprisonment had higher levels of immunity from past
      infection than the general population (19.3%, 33.0%, 17.1%, respectively, vs.
      3.0%, P < 0.05). Indigenous prisoners, non-IDUs and first-time entrants had
      significantly lower levels of vaccine-conferred immunity than the general
      population (26.4%, 26.2% and 20.7% respectively vs. 43.4%, P < 0.05). Improving
      prison-based HBV vaccination would prevent transmission in the prison setting and
      protect vulnerable members of the community who are at high risk of both
      infection and entering the prison system. 

PMID- 25600773
TI  - Characterization of Left Atrial Mechanics in Hypertrophic Cardiomyopathy and
      Essential Hypertension Using Vector Velocity Imaging.
AB  - BACKGROUND: Systemic hypertension (HTN) and hypertrophic cardiomyopathy (HCM) may
      be associated with left atrial (LA) dilation, but whether LA functional
      abnormalities are characteristic to each disease or not, is unknown. The aim of
      this study was to characterize LA mechanical changes in patients with HTN and HCM
      using vector velocity imaging (VVI). METHODS: VVI-derived longitudinal LA
      function was acquired from apical views in 76 CM patients, 33 hypertension
      patients and 30 age-matched controls. Peak atrial longitudinal strain (Esys ),
      atrial strain rate during systole (SRsys ), early diastole (SRe ), and late
      diastole (SRa ) were measured (corresponding to LA reservoir, conduit and
      contractile functions, respectively). Similar parameters were used to assess left
      ventricular (LV) function. RESULTS: LV mass and LA volume index were higher in
      HCM and HTN than in controls. Both LA Reservoir function (LA Esys SRsys ) and
      conduit function (SRe ) were more declined in HCM patients, in comparison to HTN
      patients and controls (P < 0.0001),whereas conduit function was the only function
      deteriorated in the HTN group. LA contractile function was preserved among
      patient groups. In HCM, LV Esys and SRa [P < 0.001] are independent predictors
      for LA Esys . While in hypertension, only LVMI is an independent predictor for LA
      dysfunction (P < 0.01). By receiver operating characteristic analyses, only
      atrial reservoir function was extrapolative and appeared to be accurate in
      discriminating HCM from both hypertension and controls, with LA Esys <= 33% being
      more sensitive (71.8%) and specific (75%). CONCLUSIONS: Response of LA mechanics
      to pathologic hypertrophy is entirely different. In HCM LA reservoir and conduit
      functions are more deteriorated and related to the severity of phenotype, while
      in hypertension the conduit function is chiefly affected and LA dysfunction is
      linked to a more advanced disease.

PMID- 25600774
TI  - A hierarchical meso-macroporous poly(ionic liquid) monolith derived from a single
      soft template.
AB  - A hierarchical meso-macroporous poly(ionic liquid) monolith with tunable pore
      structure is synthesized through free radical self-polymerization of 1-allyl-3
      vinylimidazolium ionic liquid by using the tri-block copolymer P123 as the soft
      template. The obtained polymeric matrix can highly disperse heteropolyanions
      through anion-exchange, exhibiting superior catalytic activity in cis-cyclooctene
      epoxidation with H2O2. 

PMID- 25600772
TI  - The effect of an amino acid beverage on glucose response and glycogen
      replenishment after strenuous exercise.
AB  - PURPOSE: We previously reported that an amino acid mixture (AA) was able to lower
      the glucose response to an oral glucose challenge in both rats and humans.
      Increased glucose uptake and glycogen storage in muscle might be associated with
      the faster blood glucose clearance. We therefore tested the effect of two
      different doses of AA provided with a carbohydrate supplement on blood glucose
      homeostasis and muscle glycogen replenishment in human subjects after strenuous
      aerobic exercise. METHODS: Ten subjects received a carbohydrate (1.2 g/kg body
      weight, CHO), CHO/HAA (CHO + 13 g AA), or CHO/LAA (CHO + 6.5 g AA) supplement
      immediately and 2 h after an intense cycling bout. Muscle biopsies were performed
      immediately and 4 h after exercise. RESULTS: The glucose responses for CHO/HAA
      and CHO/LAA during recovery were significantly lower than CHO, as was the glucose
      area under the curve (CHO/HAA 1259.9 +/- 27.7, CHO/LAA 1251.5 +/- 47.7, CHO
      1376.8 +/- 52.9 mmol/L 4 h, p < 0.05). Glycogen storage rate was significantly
      lower in CHO/HAA compared with CHO, while it did not differ significantly between
      CHO/LAA or CHO (CHO/HAA 15.4 +/- 2.0, CHO/LAA 18.1 +/- 2.0, CHO 21.5 +/- 1.4
      umol/g wet muscle 4 h). CHO/HAA caused a significantly higher insulin response
      and a greater effect on mTOR and Akt/PKB phosphorylation compared with CHO.
      Phosphorylation of AS160 and glycogen synthase did not differ across treatments.
      Likewise, there were no differences in blood lactate across treatments.
      CONCLUSIONS: The AA lowered the glucose response to a carbohydrate supplement
      after strenuous exercise. However, it was not effective in facilitating
      subsequent muscle glycogen storage.

PMID- 25600775
TI  - The intersection of detecting fetal growth restriction and patient safety.

PMID- 25600777
TI  - A role for the extracellular matrix component hyaluronan in kidney dysfunction
      during ACE-inhibitor fetopathy.
AB  - Despite data showing that inhibitors of the renin-angiotensin system increase the
      risks of fetal morbidity and dysfunctionality later in life, their use during
      pregnancy has increased. The fetopathy induced by angiotensin converting enzyme
      (ACE) inhibitors is characterized by anuria, hypotension and growth restriction,
      but can also be associated with pulmonary hypoplasia. In the kidney, this
      fetopathy includes atrophy of the medulla, reduced number of glomeruli,
      developmental lesions of tubules and vessels, tubulointerstitial inflammation and
      extracellular matrix accumulation. Although angiotensin II (Ang II) inhibition
      during nephrogenesis interferes with normal growth and development, this review
      will focus on effects of the heavily accumulated matrix component hyaluronan
      (HA). An important mechanism of HA accumulation during nephrogenesis is
      disruption of its normal reduction as a consequence of lack of Ang II activation
      of hyaluronidase. Hyaluronan has very large water-attracting properties and is
      pro-inflammatory when fragmented. The ensuing inflammation and interstitial
      oedema affect kidney function. Hyaluronan is colocalized with CD44 overexpression
      and infiltrating immune cells. These properties make HA a plausible contributor
      to the observed structural and functional kidney defects associated with the
      fetopathy. Available data support an involvement of HA in kidney dysfunction of
      the foetus and during adulthood due to the physico-chemical characteristics of
      HA. No clinical treatment for HA accumulation exists. Treatment with the HA
      degrading enzyme hyaluronidase and an HA synthesis inhibitor has been tested
      successfully in experimental models in the kidney, heart and pancreas. Reduced HA
      accumulation to reduce interstitial oedema and inflammation may improve organ
      function, but this concept needs to be tested in a controlled study before causal
      relationships can be established. 

PMID- 25600779
TI  - The TITAN-AMI multicenter registry evaluating the usage of Titan2 stent in
      patients with ST segment elevation myocardial infarction. Final result at 12
      month follow-up.
AB  - AIM: Primary percutaneous coronary intervention with stent implantation is the
      recommended treatment for patients with ST elevation myocardial infarction
      (STEMI). Data from randomised trials showed good performance by a titanium-nitric
      oxide coated stent in this context. The aim of this study was to confirm these
      data. METHODS: A multicentre registry was compiled in 23 hospitals in Spain in an
      all-comers population. We selected patients with STEMI from a global Titan AMI
      registry that included patients with acute coronary syndrome. Primary endpoint
      was the composite of cardiac death, non-fatal myocardial infarction, stent
      thrombosis and target lesion revascularisation, at 12-month follow-up. RESULTS:
      The study included 893 patients with STEMI. We included all possibilities for
      PCI: 86.6% primary, 5% facilitated after successful fibrinolysis and 8.4% rescue
      PCI after failed fibrinolysis. The primary endpoint was reached in 8.4% of the
      patients: cardiac death 2.7%, reinfarction 3.4%, target lesion revascularisation
      3.5% and definite or probable stent thrombosis 2.8%. The majority of stent
      thromboses presented in the first 30 days after PCI. CONCLUSION: A bioactive
      stent (titanium-nitric-oxide coated stent) is a possible alternative for the
      treatment of patients with STEMI. One-year follow-up showed better results than
      those presented by a regular bare-metal stent or first-generation drug-eluting
      stent in terms of stent thrombosis.

PMID- 25600778
TI  - The unexpected role of polyubiquitin chains in the formation of fibrillar
      aggregates.
AB  - Ubiquitin is known to be one of the most soluble and stably folded intracellular
      proteins, but it is often found in inclusion bodies associated with various
      diseases including neurodegenerative disorders and cancer. To gain insight into
      this contradictory behaviour, we have examined the physicochemical properties of
      ubiquitin and its polymeric chains that lead to aggregate formation. We find that
      the folding stability of ubiquitin chains unexpectedly decreases with increasing
      chain length, resulting in the formation of amyloid-like fibrils. Furthermore,
      when expressed in cells, polyubiquitin chains covalently linked to EGFP also form
      aggregates depending on chain length. Notably, these aggregates are selectively
      degraded by autophagy. We propose a novel model in which the physical and
      chemical instability of polyubiquitin chains drives the formation of fibrils,
      which then serve as an initiation signal for autophagy. 

PMID- 25600780
TI  - Advanced therapeutic options in pulmonary hypertension: who, what and when?
AB  - Pulmonary hypertension (PH) is the common hemodynamic consequence of various
      pathophysiologic mechanisms. Since the publication of the most current American
      and European guidelines (2009) new agents were introduced into the clinical arena
      while data regarding former drugs has been substantiated. The therapeutic
      endeavor of evaluating new therapies for PH targets patients based on their PH
      type and symptom severity with the hope to demonstrate hemodynamic and functional
      benefits along with reduction in morbidity and mortality. Although patients'
      outcomes (predominantly among type I and IV) have improved, the hemodynamic and
      symptomatic benefit is modest and not uniform. The purpose of this review is to
      objectively assess the benefits of the currently available dedicated agents. It
      is our hope that with early detection and careful individual titration of new
      combination therapy in expert hands, we will better serve a larger proportion of
      our PH patients. 

PMID- 25600781
TI  - Sleep problems in children with autism spectrum disorder: examining the
      contributions of sensory over-responsivity and anxiety.
AB  - OBJECTIVES: Children with autism spectrum disorder (ASD) are at high risk for
      sleep problems. Previous research suggests that sensory problems and anxiety may
      be related to the development and maintenance of sleep problems in children with
      ASD. However, the relationships among these co-occurring conditions have not been
      previously studied. The current study examined the interrelations of these
      symptoms in a large well-characterized sample of children and adolescents with
      ASD. METHODS: The current study examined the relationships among sleep problems,
      sensory over-responsivity, and anxiety in 1347 children enrolled in the Autism
      Speaks Autism Treatment Network. The primary measures included the Children's
      Sleep Habits Questionnaire, the Child Behavior Checklist, and the Short Sensory
      Profile. RESULTS: In bivariate correlations and multivariate path analyses,
      anxiety was associated with all types of sleep problems (ie, bedtime resistance,
      sleep-onset delay, sleep duration, sleep anxiety, and night wakings; p < 0.01 to
      p < 0.001; small to medium effect sizes). Sensory over-responsivity (SOR) was
      correlated with all sleep problems in bivariate analyses (p < 0.01 to p < 0.001;
      small effect sizes). In multivariate path models, SOR remained significantly
      associated with all sleep problems except night awakenings for older children,
      while SOR was no longer significantly associated with bedtime resistance or sleep
      anxiety for younger children. CONCLUSIONS: Children with ASD who have anxiety and
      SOR may be particularly predisposed to sleep problems. These findings suggest
      that some children with ASD and sleep disturbance may have difficulties with
      hyperarousal. Future research using physiological measures of arousal and
      objective measures of sleep are needed.

PMID- 25600782
TI  - Pain perception in narcolepsy with cataplexy patients.

PMID- 25600783
TI  - Incidence of sudden unexpected death in nocturnal frontal lobe epilepsy: a cohort
      study.
AB  - OBJECTIVE: Most cases of sudden unexpected death in epilepsy (SUDEP) follow a
      seizure, and most deaths occur while people are in bed, presumably sleeping.
      Nocturnal seizures are reported to be a risk factor for SUDEP. People with
      nocturnal frontal lobe epilepsy (NFLE) have seizures predominantly or exclusively
      during sleep, often many times per night. The present study aimed to assess
      whether NFLE represents a high-risk condition for SUDEP. METHODS: The present
      study retrospectively assessed the incidence of SUDEP in a cohort reconstructed
      from a dedicated database of consecutive patients referred to the Epilepsy and
      Sleep Centres of the Institute of Neurological Sciences of Bologna from 1980 to
      2012 with: (1) a diagnosis of NFLE, (2) at least 90% of seizures during sleep,
      and (3) at least one-year of follow-up. RESULTS: One hundred and three people
      were included. The median time from seizure onset to last observation was 26
      years, equal to a follow-up of 2789 person-years. One person died of SUDEP during
      the follow-up period. The incidence rate of SUDEP was 0.36 per 1000 person-years
      (95% CI 0.01 to 2.0). CONCLUSIONS: The incidence of SUDEP in the participant
      population was not higher than the rates previously reported in prevalent
      epilepsy populations (0.4 to 2.3 per 1000 person-years). The low prevalence of
      SUDEP might reflect the low occurrence of generalised tonic-clonic seizures in
      people with NFLE.

PMID- 25600784
TI  - Dietary patterns and sleep symptoms in Japanese workers: the Furukawa Nutrition
      and Health Study.
AB  - OBJECTIVE: Experimental studies have shown that some nutrients are involved in
      initiating and maintaining sleep, but epidemiological evidence on overall dietary
      patterns and insomnia is scarce. We investigated the relationship between dietary
      patterns and sleep symptoms in a Japanese working population. METHODS: The
      participants were 2025 workers, aged 18-70 years, who participated in a health
      survey during a periodic checkup in 2012 and 2013. Dietary intake was assessed
      with a self-administered diet history questionnaire. Dietary patterns were
      extracted by principal component analysis on the basis of the energy-adjusted
      intake of 52 food and beverage items. Sleep duration, difficulty initiating and
      maintaining sleep, and poor quality of sleep were self-reported. Logistic
      regression was used to estimate the odds ratios of each sleep symptom according
      to quartile categories of each dietary pattern with adjustment for potential
      confounding variables. RESULTS: We identified three major dietary patterns. A
      healthy pattern, characterized by a high intake of vegetables, mushrooms,
      potatoes, seaweeds, soy products, and eggs, was associated with a decreased
      prevalence of difficulty initiating sleep once or more a week (P for trend =
      0.03); the multivariate adjusted odds ratio in the highest quartile of this score
      compared with the lowest was 0.75 (95% CI: 0.57-0.99). This association persisted
      after the exclusion of individuals with severe depressive symptoms. However,
      there was no significant association with difficulty initiating sleep at least
      three times a week. CONCLUSIONS: Our findings suggest that a healthy dietary
      pattern may be associated with difficulty initiating sleep at least once a week.

PMID- 25600786
TI  - Designing an algorithm to preserve privacy for medical record linkage with error
      prone data.
AB  - BACKGROUND: Linking medical records across different medical service providers is
      important to the enhancement of health care quality and public health
      surveillance. In records linkage, protecting the patients' privacy is a primary
      requirement. In real-world health care databases, records may well contain errors
      due to various reasons such as typos. Linking the error-prone data and preserving
      data privacy at the same time are very difficult. Existing privacy preserving
      solutions for this problem are only restricted to textual data. OBJECTIVE: To
      enable different medical service providers to link their error-prone data in a
      private way, our aim was to provide a holistic solution by designing and
      developing a medical record linkage system for medical service providers.
      METHODS: To initiate a record linkage, one provider selects one of its
      collaborators in the Connection Management Module, chooses some attributes of the
      database to be matched, and establishes the connection with the collaborator
      after the negotiation. In the Data Matching Module, for error-free data, our
      solution offered two different choices for cryptographic schemes. For error-prone
      numerical data, we proposed a newly designed privacy preserving linking algorithm
      named the Error-Tolerant Linking Algorithm, that allows the error-prone data to
      be correctly matched if the distance between the two records is below a
      threshold. RESULTS: We designed and developed a comprehensive and user-friendly
      software system that provides privacy preserving record linkage functions for
      medical service providers, which meets the regulation of Health Insurance
      Portability and Accountability Act. It does not require a third party and it is
      secure in that neither entity can learn the records in the other's database.
      Moreover, our novel Error-Tolerant Linking Algorithm implemented in this software
      can work well with error-prone numerical data. We theoretically proved the
      correctness and security of our Error-Tolerant Linking Algorithm. We have also
      fully implemented the software. The experimental results showed that it is
      reliable and efficient. The design of our software is open so that the existing
      textual matching methods can be easily integrated into the system. CONCLUSIONS:
      Designing algorithms to enable medical records linkage for error-prone numerical
      data and protect data privacy at the same time is difficult. Our proposed
      solution does not need a trusted third party and is secure in that in the linking
      process, neither entity can learn the records in the other's database.

PMID- 25600787
TI  - [Skincare in premature newborn infants: a joint goal for dermatologists and
      neonatologists].

PMID- 25600785
TI  - Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic
      culling in mouse hearts and cultured fibroblasts.
AB  - How mitochondrial dynamism (fission and fusion) affects mitochondrial quality
      control is unclear. We uncovered distinct effects on mitophagy of inhibiting Drp1
      mediated mitochondrial fission versus mitofusin-mediated mitochondrial fusion.
      Conditional cardiomyocyte-specific Drp1 ablation evoked mitochondrial
      enlargement, lethal dilated cardiomyopathy, and cardiomyocyte necrosis.
      Conditionally ablating cardiomyocyte mitofusins (Mfn) caused mitochondrial
      fragmentation with eccentric remodeling and no cardiomyocyte dropout. Parallel
      studies in cultured murine embryonic fibroblasts (MEFs) and in vivo mouse hearts
      revealed that Mfn1/Mfn2 deletion provoked accumulation of defective mitochondria
      exhibiting an unfolded protein response, without appropriately increasing
      mitophagy. Conversely, interrupting mitochondrial fission by Drp1 ablation
      increased mitophagy and caused a generalized loss of mitochondria. Mitochondrial
      permeability transition pore (MPTP) opening in Drp1 null mitochondria was
      associated with mitophagy in MEFs and contributed to cardiomyocyte necrosis and
      dilated cardiomyopathy in mice. Drp1, MPTP, and cardiomyocyte mitophagy are
      functionally integrated. Mitochondrial fission and fusion have opposing roles
      during in vivo cardiac mitochondrial quality control.

PMID- 25600788
TI  - [Iatrogenic skin lesions: a prospective study in premature infants born at less
      than 33 weeks of amenorrhea at Besancon university hospital].
AB  - BACKGROUND: Advances in neonatology have markedly improved prognosis for
      premature babies in recent years. However, they have also entailed the need for
      recourse to considerable intensive care involving potentially iatrogenic
      diagnostic and therapeutic acts. Among the resulting iatrogenic events, cutaneous
      lesions are the most frequent but have been the subject of very few studies. Our
      own study thus aimed to assess the rate of iatrogenic cutaneous events in
      premature infants born at less than 33 weeks of amenorrhea and hospitalised at
      Besancon university hospital and to identify the factors associated with the
      occurrence of these events. PATIENTS AND METHODS: This was a prospective study
      carried out in the department of paediatric intensive care and neonatology at
      Besancon university hospital between May 2011 and April 2012. All babies born
      before 33 weeks of amenorrhea hospitalised over this period were included. An
      iatrogenic event was defined as "an adverse event related to a medical
      procedure". Iatrogenic cutaneous events were reported to the dermatologist by
      medical and paramedical staff. RESULTS: One hundred and thirthteen newborn babies
      were included during the study period. Twenty-six iatrogenic cutaneous events
      were recorded in 19 infants, representing 16.8% of the population involved: nine
      were associated with ventilation techniques, six with the use of intravenous
      catheters, five with electrodes, two involved pressure sores, two were linked to
      the birth, one to disinfectants and one to dressings. The main risk factor was
      low birth weight (P=0.016). High prematurity and the duration of ventilation
      increased the risk, although not significantly. The death rate was higher in
      children with iatrogenic events but the difference was not significant. The
      duration of hospitalisation was unaffected by the presence or absence of an
      iatrogenic event. CONCLUSION: The frequency of iatrogenic cutaneous events is
      high in hospital departments in charge of very premature infants. Awareness by
      the medical and paramedical staff of the frequency of such iatrogenic events
      should improve the quality of care.

PMID- 25600789
TI  - [Indoor tanning: motivations and beliefs among users and non-users in the
      population of Lille (Northern France)].
AB  - BACKGROUND: Uncontrolled use of tanning beds is a major public health problem.
      The role of UV in skin carcinogenesis has in fact been clearly demonstrated.
      AIMS: The main purpose of the study was to assess the motivations and beliefs of
      the population concerning the use of indoor tanning. The secondary objectives
      were to compare the knowledge of users and non-users and to screen for addiction
      criteria among users. PATIENTS AND METHODS: This was a transversal descriptive
      study conducted between April and June 2013 in Lille town center. The motivations
      of the participants were determined using a multiple-choice questionnaire. A
      Likert scale was used to assess beliefs and an m-CAGE questionnaire was used to
      screen for addiction. RESULTS: Of the 200 respondents, 30% (n=60) had used
      tanning beds in a non-medical setting. The median age of first use was 23 years
      (15-59). 11.7% of respondents had started before the authorised age of 18 years.
      "To prepare the skin for exposure to the sun" was the main reason given (68.3%)
      for use of tanning beds. The population was aware that use of such apparatus
      favours onset of skin cancer and ageing of the skin. Users were more convinced
      than non-users that UV cabins "prepare the skin for exposure to the sun" (75% vs.
      49.6%, P=0.0009) and that they "favour skin cancer" (56.9% against 36.2%,
      P=0.0444). Addictive behaviour was detected in 3.3% (2/60) of users. CONCLUSION:
      Users are aware of the carcinogenic risk of UV cabins but expose themselves to
      such risk, as they believe it prepares their skin for sun exposure.

PMID- 25600790
TI  - [Efficacy of pulsed-dye laser on residual red lesions of cutaneous
      leishmaniasis].
AB  - BACKGROUND: Cutaneous leishmaniasis caused by Leishmania tropica can leave
      troublesome and unsightly lesions. Treatment of these scars remains difficult.
      Pulsed-dye laser (PDL) is one therapeutic approach that may improve the clinical
      appearance of erythematosus lesions. The purpose of this retrospective study was
      to evaluate the effectiveness of PDL on the residual red lesions of erythematous
      facial leishmaniasis in three patients. PATIENTS AND METHODS: Case no. 1: a 14
      year-old girl presented an ulcerative and erythematous nodular lesion on her left
      cheek. One month after treatment, an erythematous lesion measuring 3 cm persisted
      on the patient's cheek, without atrophy or hyperpigmentation. PDL 595nm was used
      at the following settings: duration: 3ms; spot size: 7mm; energy: 8 j/cm(2). Case
      no. 2: a 43-year-old woman presented an erythematous papular lesion on her right
      cheek. Following treatment, a 4-cm hypertrophic, red telangiectasic lesion
      remained. PDL 595nm was used with the following settings: pulse duration: 3 ms;
      spot-size: 10mm; energy: 8 j/cm(2). Case no. 3: a 60-year-old woman presented an
      erythematous papular lesion on her cheek. After treatment, an infiltrated
      erythematous macule with surface telangiectasia measuring 3.5cm remained. PDL
      595nm was also given using the following settings: pulse duration: 3 ms; spot
      size: 10mm; energy: 8 j/cm(2). All three patients underwent three sessions of
      PDL. The erythematous and telangiectasic lesions showed improvement after the
      initial session and had completely disappeared after the third session. Post
      laser purpura subsided within around 10 days. Therapeutic response was assessed
      clinically by comparing photographs taken before and after treatment and follow
      up lasted 12 months. DISCUSSION: Cutaneous leishmaniasis caused by L. tropica is
      endemo-epidemic in Morocco. A number of treatments are available for red residual
      lesions but thanks to its effect on erythematous and vascular lesions, PDL has
      been shown to provide the most reproducibly good results and is the laser method
      of choice for this type of scar. A recent study of the dermoscopic features of DL
      identified the presence of vascular patterns in 100% of cases in this infection,
      which may account for the efficacy of PDL. PDL results in selective thermolysis
      that destroys small vessels. Our study showed improvement with PDL regarding scar
      size, pliability, erythema and texture. Further larger-scale studies could better
      determine the place of PDL in treating the sequelae of cutaneous leishmaniasis.

PMID- 25600791
TI  - [Clinical characteristics of nail lichen planus and follow-up: a descriptive
      study of 20 patients].
AB  - BACKGROUND: Nail lichen planus (NLP) occurs in 10% of patients with disseminated
      disease but it can also occur in isolation. The outcome of treatment is usually
      disappointing and data about its long-term prognosis are lacking. STUDY AIM: To
      study clinical features, response to treatment and follow-up of a series of 20
      patients with NLP. PATIENTS AND METHODS: A descriptive study was conducted of 20
      patients with histologically confirmed NLP seen at consultations for nail
      disorders between September 2009 and April 2013. RESULTS: The mean age was 35
      years (9-56 years) with no gender preponderance. Forty percent of patients were
      children. Stress was an evident triggering factor in 20% of patients. The mean
      duration was around 48 months (2 months to 10 years). Only 25% of patients had
      extra-ungual lesions. All 20 nails were affected in 55% of patients. Nail matrix
      involvement was observed in 85% of cases and 55% had nail-bed involvement. Twenty
      five percent of patients were presenting severe involvement such as pterygium or
      anonychia. Intramuscular corticosteroids were given to 10 patients. In 80% of
      patients, the NLP was limited or regressed rapidly from the third injection. The
      average follow-up was 24 months. DISCUSSION: Our study highlights the frequency
      of paediatric forms and of often aesthetically unacceptable nail scarring. Early
      diagnosis of NLP, notably in children, would allow initiation of adequate
      treatment that could perhaps limit the risk of such sequelae.

PMID- 25600793
TI  - [Drug patch tests in the investigation of a fixed drug eruption subsequent to 2
      courses of cyclophosphamide in combination with mesna].
AB  - BACKGROUND: When fixed drug eruption occurs following use of cyclophosphamide and
      mesna, it is difficult to establish which drug is responsible. We report a new
      case of patch tests that resulted in withdrawal of mesna and enabled continued
      treatment with cyclophophamide. PATIENTS AND METHODS: A 57-year-old female
      patient with multiple sclerosis presented increasingly severe cutaneous lesions
      after successive courses of cyclophosphamide. Twenty-four hours after her latest
      treatment, she presented at the ER with a worse eruption than those to date and
      including facial lesions. The clinical diagnosis was a fixed drug eruption, and
      patch tests for mesna one month later were positive. CONCLUSION: Fixed drug
      eruption always occurs after recurrent treatment and the investigation must be
      precise. Patch tests may be used to determine which drug could be responsible.
      The most conclusive test comprises withdrawal of the incriminated drug with no
      further signs of drug eruption on resumption of the other medication.

PMID- 25600792
TI  - [Recommendations for genetic testing and management of individuals genetically at
      risk of cutaneous melanoma].
AB  - Cutaneous melanoma is a multifactorial disease resulting from both environmental
      and genetic factors. Five susceptibility genes have been identified over the past
      years, comprising high-risk susceptibility genes (CDKN2A, CDK4, and BAP1 genes)
      and intermediate-risk susceptibility genes (MITF, and MC1R genes). The aim of
      this expert consensus was to define clinical contexts justifying genetic
      analyses, to describe the conduct of these analyses, and to propose surveillance
      recommendations. Given the regulatory constraints, it is recommended that
      dermatologists work in tandem with a geneticist. Genetic analysis may be
      prescribed when at least two episodes of histologically proven invasive cutaneous
      melanoma have been diagnosed before the age of 75 years in two 1st or 2nd degree
      relatives or in the same individual. The occurrence in the same individual or in
      a relative of invasive cutaneous melanoma with ocular melanoma, pancreatic
      cancer, renal cancer, mesothelioma or a central nervous system tumour are also
      indications for genetic testing. Management is based upon properly managed
      photoprotection and dermatological monitoring according to genetic status.
      Finally, depending on the mutated gene and the familial history, associated
      tumour risks require specific management (e.g. ocular melanoma, pancreatic
      cancer). Due to the rapid progress in genetics, these recommendations will need
      to be updated regularly. 

PMID- 25600794
TI  - [PENS (papular epidermal nevus with "skyline" basal cell layer)].
AB  - BACKGROUND: PENS is a rare neuro-cutaneous syndrome that has been recently
      described. It involves one or more congenital epidermal hamartomas of the papular
      epidermal nevus with "skyline" basal cell layer type (PENS) as well as non
      specific neurological anomalies. Herein, we describe an original case in which
      the epidermal hamartomas are associated with autism spectrum disorder (ASD).
      PATIENTS AND METHODS: A 6-year-old boy with a previous history of severe ASD was
      referred to us for asymptomatic pigmented congenital plaques on the forehead and
      occipital region. Clinical examination revealed a light brown verrucous
      mediofrontal plaque in the form of an inverted comma with a flat striated surface
      comprising coalescent polygonal papules, and a clinically similar round occipital
      plaque. Repeated biopsies revealed the presence of acanthotic epidermis covered
      with orthokeratotic hyperkeratosis with occasionally broadened epidermal crests
      and basal hyperpigmentation, pointing towards an anatomoclinical diagnosis of
      PENS. DISCUSSION: A diagnosis of PENS hamartoma was made on the basis of the
      clinical characteristics and histopathological analysis of the skin lesions. This
      condition is defined clinically as coalescent polygonal papules with a flat or
      rough surface, a round or comma-like shape and light brown coloring.
      Histopathological examination showed the presence of a regular palisade "skyline"
      arrangement of basal cell epidermal nuclei which, while apparently pathognomonic,
      is neither a constant feature nor essential for diagnosis. Association of a PENS
      hamartoma and neurological disorders allows classification of PENS as a new
      keratinocytic epidermal hamartoma syndrome. The early neurological signs, of
      varying severity, are non-specific and include psychomotor retardation, learning
      difficulties, dyslexia, hyperactivity, attention deficit disorder and epilepsy.
      There have been no reports hitherto of the presence of ASD as observed in the
      case we present. CONCLUSION: This new case report of PENS confirms the autonomous
      nature of this neuro-cutaneous disorder associated with keratinocytic epidermal
      hamartoma syndromes.

PMID- 25600795
TI  - [Erythema nodosum during the course of idiopathic granulomatous mastitis].
AB  - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a benign, aseptic
      inflammatory disease of unknown origin, which must be distinguished from tumoral
      and infectious processes that affect the breast, including tuberculosis. IGM is a
      rare cause of erythema nodosum, but it is useful for dermatologists to be aware
      of this association. PATIENTS AND METHODS: A 32-year-old nulliparous woman
      presented with erythema nodosum, arthralgia and fever. On examination, she had a
      firm and painful mass of 5cm in the right breast with retraction and axillary
      adenopathy. The breast lump developed gradually over the preceding 4 months.
      Although two biopsies showed no evidence of atypical cells, inflammatory areas
      and a granulomatous process were seen. Culture of breast tissue for mycobacteria
      was negative. A diagnostic of idiopathic granulomatous mastitis was made.
      Systemic corticosteroids led to a reduction in size of the mass, but relapse
      occurred in the contralateral breast on dose-reduction of the corticosteroids.
      DISCUSSION: IGM is a rare disease of unknown aetiology. Diagnosis is based on
      characteristic histological features and exclusion of other granulomatous
      diseases. Extra-mammary signs are rare and include erythema nodosum, arthralgia
      and episcleritis. Management is poorly codified.

PMID- 25600796
TI  - [Characteristics of neurofibromatosis type 1 in Martinique: a preliminary
      report].

PMID- 25600797
TI  - [Diaper dermatitis].

PMID- 25600798
TI  - [Superficial spreading melanoma].

PMID- 25600799
TI  - [Contribution of reflectance confocal microscopy in the diagnosis of extra
      mammary Paget's disease].

PMID- 25600800
TI  - [Adverse effects of Aldara((r)): polymorphous erythema and chronic ulceration].

PMID- 25600801
TI  - Relationship between fluoride release rate and anti-cariogenic biofilm activity
      of glass ionomer cements.
AB  - OBJECTIVES: The aim of this study was to evaluate acidogenicity and composition
      of Streptococcus mutans biofilms on glass ionomer cements (GICs) and then to
      determine the relationship between the anti-S. mutans biofilm activity and
      fluoride release rate of the GICs. METHODS: S. mutans biofilms were formed on
      discs prepared using five commercial GICs. Acid production and fluoride release
      rates of the biofilms on the GIC discs during biofilm formation (0-94 h) were
      determined. Next, 94-h-old S. mutans biofilms on GIC discs were analyzed to
      evaluate the biofilm composition (dry weight, bacterial cell number, and extra
      cellular polysaccharide (EPS) amount) using microbiological, biochemical, and
      confocal laser scanning microscopy (CLSM) methods. Lastly, relationships between
      the fluoride release rate and changes in acidogenicity and composition of the
      biofilms were determined using a linear-fitting procedure. RESULTS: All of the
      tested GICs released fluoride ions. Of the GICs, the two that showed the highest
      fluoride release rates strongly affected acidogenicity, dry weight, and EPS
      formation of the biofilms. Furthermore, they reduced the bacterial and EPS bio
      volumes and EPS thickness. However, the number of colony forming units (CFUs) of
      the biofilms was higher than that of the control. Generally, changes in the
      acidogenicity and composition (except for CFU count) of the biofilms on the GICs
      followed a negative linear-pattern of fluoride release rate-dependence (R=-0.850
      to -0.995, R(2)=0.723-0.990). SIGNIFICANCE: These results suggest that the anti
      cariogenic biofilm activity of GICs is closely correlated with their fluoride
      release rate during biofilm formation.

PMID- 25600802
TI  - Silencing clusterin gene transcription on effects of multidrug resistance
      reversing of human hepatoma HepG2/ADM cells.
AB  - Abnormal clusterin (CLU) expression is associated with multidrug resistance (MDR)
      of hepatocellular carcinoma (HCC). In the present study, the CLU expression was
      analyzed in human hepatoma cells and chemoresistant counterpart HepG2/ADM cells.
      Compared with L02 cells, the overexpression of cellular CLU was identified in
      HepG2, HepG2/ADM, SMMC7721, Hep3B ,and PLC cells and relatively lower expression
      in Bel-7404, SNU-739, and MHCC97H cells. Specific short hairpin RNAs (shRNAs) to
      silence CLU gene transcription were designed, and the most effective sequences
      were screened. After the HepG2/ADM cells transfected with shRNA-1, the inhibition
      of CLU expression was 73.68 % at messenger RNA (mRNA) level by real-time
      quantitative RT-PCR with obvious enhancement in cell chemosensitivity, increasing
      apoptosis induced by doxorubicin using fluorescence kit, and Rh-123 retention
      qualified with flow cytometry. Knockdown CLU also significantly decreased the
      drug efflux pump activity through the depression of MDR1/P-glycoprotein (q =
      11.739, P < 0.001). Moreover, silencing CLU led to downregulation of beta-catenin
      (q = 13.544, P = 0.001), suggesting that downregulation of CLU might be a key
      point to reverse multidrug resistance of HepG2/ADM cells.

PMID- 25600803
TI  - Endothelial-monocyte-activating polypeptide II induces rat C6 glioma cell
      apoptosis via the mitochondrial pathway.
AB  - The present study was performed to examine whether Endothelial-monocyte
      activating polypeptide II (EMAP II) could inhibit glioma growth by inducing rat
      brain glioma C6 cells apoptosis. The results revealed that the EMAP II decreased
      cell viability of rat C6 glioma cells in a time-dependent manner. Apoptotic
      proportion was increased gradually after EMAP II. EMAP II induced the decrease in
      mitochondrial membrane potential and the release of cytochrome c into the
      cytosol, followed by activation of caspase-9 and caspase-3. Meanwhile, EMAP II
      induced apoptosis was accompanied by an increase of reactive oxygen species
      (ROS). The significant up-regulation in the expressions of Bax and Apaf-1 as well
      as down-regulation in the expression of Bcl-2 was observed. The time course
      change of ROS was prior to the changes of above investigated indexes. All of
      these results strongly suggest that EMAP II could induce rat C6 glioma cells
      apoptosis via the mitochondrial pathway, and ROS, Bax/Bcl-2 might be involved in
      this processing.

PMID- 25600804
TI  - Basic amino acid residues located in the N-terminal region of BEND3 are essential
      for its nuclear localization.
AB  - BEN domain-containing protein 3 (BEND3) has recently been reported to function as
      a heterochromatin-associated protein in transcriptional repression in the
      nucleus. BEND3 should have nuclear localization signals (NLSs) to localize to the
      nucleus in light of its molecular weight, which is higher than that allowed to
      pass through nuclear pore complexes. We here analyzed the subcellular
      localization of deletion/site-directed mutants of human BEND3 by an
      immunofluorescence assay in an attempt to identify the amino acids essential for
      its nuclear localization. We found that three basic amino acid residues located
      in the N-terminal region of BEND3 (BEND356-58, KRK) are essential, suggesting
      that these residues play a role as a functional NLS. These results provide
      valuable information for progressing research on BEND3.

PMID- 25600805
TI  - Heparin cofactor II is degraded by heparan sulfate and dextran sulfate.
AB  - Heparan sulfate normally binds to heparin cofactor II and modulates the
      coagulation pathway by inhibiting thrombin. However, when human heparin cofactor
      II was incubated with heparan sulfate, heparin cofactor II became degraded. Other
      glycosaminoglycans were tested, including hyaluronic acid, chondroitin sulfates,
      dermatan sulfate, and heparin, but only dextran sulfate also degraded heparin
      cofactor II. Pretreatment of heparan sulfate with heparinase reduced its heparin
      cofactor II-degrading activity. Heparan sulfate and dextran sulfate diminished
      the thrombin inhibitory activity of heparin cofactor II. Other serpins, including
      antithrombin III and pigment epithelium-derived factor, were also degraded by
      heparan sulfate. This is the first evidence of acidic polysaccharides exhibiting
      protein-degrading activity without the aid of other proteins. 

PMID- 25600806
TI  - Midazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich
      microdomains in presynaptic membranes through the gamma-aminobutyric acid A
      receptor.
AB  - Recent studies have suggested that a positive correlation exists between surgical
      interventions performed under general anesthesia and the risk of developing
      Alzheimer's disease (AD) in the late postoperative period. It has been reported
      that amyloid beta-protein (Alphabeta) fibrillogenesis, which is closely related
      to AD, is accelerated by exposure to anesthetics. However, the mechanisms
      underlying these effects remain uncertain. This study was designed to investigate
      whether the anesthetic midazolam affects Alphabeta fibrillogenesis, and if so,
      whether it acts through GM1 ganglioside (GM1) on the neuronal surface. Midazolam
      treatment decreased GM1 expression in the detergent-resistant membrane
      microdomains of neurons, and these effects were regulated by the gamma
      aminobutyric acid-A receptor. Midazolam inhibited Alphabeta fibril formation from
      soluble Alphabeta on the neuronal surface. In addition, midazolam suppressed GM1
      induced fibril formation in a cell-free system. Moreover, midazolam inhibited the
      formation of Alphabeta assemblies in synaptosomes isolated from aged mouse
      brains. These finding suggested that midazolam has direct and indirect inhibitory
      effects on Alphabeta fibrillogenesis. 

PMID- 25600807
TI  - TRAM1 protect HepG2 cells from palmitate induced insulin resistance through ER
      stress-JNK pathway.
AB  - Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of
      insulin resistance. Chronic endoplasmic reticulum (ER) stress is a major
      contributor to obesity-induced insulin resistance in the liver. With high-fat
      feeding (HFD), FFAs can activate chronic endoplasmic reticulum (ER) stress in
      target tissues, initiating negative crosstalk between FFAs and insulin signaling.
      However, the molecular link between insulin resistance and ER stress remains to
      be identified. We here reported that translocating chain-associated membrane
      protein 1 (TRAM1), an ER-resident membrane protein, was involved in the onset of
      insulin resistance in hepatocytes. TRAM1 was significantly up-regulated in
      insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In
      addition, we showed that depletion of TRAM1 led to hyperactivation of CHOP and
      GRP78, and the activation of downstream JNK pathway. Given the fact that the
      activation of ER stress played a facilitating role in insulin resistance, the
      phosphorylation of Akt and GSK-3beta was also analyzed. We found that depletion
      of TRAM1 markedly attenuated the phosphorylation of Akt and GSK-3beta in the
      cells. Moreover, application with JNK inhibitor SP600125 reversed the effect of
      TRAM1 interference on Akt phosphorylation. The accumulation of lipid droplets and
      expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also
      determined and found to display a similar tendency with the phosphorylation of
      Akt. Glucose uptake assay indicated that knocking down TRAM1 augmented PA-induced
      down-regulation of glucose uptake, and inhibition of JNK using SP600125 could
      block the effect of TRAM1 on glucose uptake. These data implicated that TRAM1
      might protect HepG2 cells against PA-induced insulin resistance through
      alleviating ER stress.

PMID- 25600808
TI  - Dissociation of glucocerebrosidase dimer in solution by its co-factor, saposin C.
AB  - Mutations in the gene for the lysosomal enzyme glucocerebrosidase (GCase) cause
      Gaucher disease and are the most common risk factor for Parkinson disease (PD).
      Analytical ultracentrifugation of 8 MUM GCase shows equilibrium between monomer
      and dimer forms. However, in the presence of its co-factor saposin C (Sap C),
      only monomer GCase is seen. Isothermal calorimetry confirms that Sap C associates
      with GCase in solution in a 1:1 complex (Kd = 2.1 +/- 1.1 MUM). Saturation cross
      transfer NMR determined that the region of Sap C contacting GCase includes
      residues 63-66 and 74-76, which is distinct from the region known to enhance
      GCase activity. Because alpha-synuclein (alpha-syn), a protein closely associated
      with PD etiology, competes with Sap C for GCase binding, its interaction with
      GCase was also measured by ultracentrifugation and saturation cross-transfer.
      Unlike Sap C, binding of alpha-syn to GCase does not affect multimerization.
      However, adding alpha-syn reduces saturation cross-transfer from Sap C to GCase,
      confirming displacement. To explore where Sap C might disrupt multimeric GCase,
      GCase x-ray structures were analyzed using the program PISA, which predicted
      stable dimer and tetramer forms. For the most frequently predicted multimer
      interface, the GCase active sites are partially buried, suggesting that Sap C
      might disrupt the multimer by binding near the active site.

PMID- 25600809
TI  - Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis.
AB  - Matrix metalloproteinases (MMPs) are zinc (Zn(2+)) and calcium (Ca(2+)) dependant
      endopeptidases, capable of degradation of numerous components of the
      extracellular matrix. Cadmium (Cd(2+)) is a well known environmental contaminant
      which could impair the activity of MMPs. In this sense, this study was conducted
      to evaluate if Cd(2+) intake inhibits these endopeptidases activities at the rat
      prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9
      at gelatinolytic assays when present in the incubation buffer. To investigate
      this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n =
      9), or 15 ppm CdCl2 diluted in drinking water, during 10 weeks (n = 9) and 20
      weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal
      prostate, and testicles were removed. These tissue samples were processed for
      protein extraction and subjected to gelatin zymography evaluation. Additionally,
      we performed an experiment of gelatin zymography in which 5 MUM or 2 mM cadmium
      chloride (CdCl2) was directly dissolved at the incubation buffer, using the
      prostatic tissue samples from untreated animals that exhibited the highest MMP2
      and MMP9 activities in the previous experiment. We have found that CdCl2 intake
      in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p <
      0.05) at the ventral prostate and testis, respectively, in Cd(2+) treated animals
      when compared to controls. Moreover, the activities of the referred enzymes were
      80% and 100% inhibited by 5 MUM and 2 mM of CdCl2, respectively, even in the
      presence of 10 mM of CaCl2 within the incubation buffer solution. These important
      findings demonstrate that environmental cadmium contamination may deregulate the
      natural balance in the extracellular matrix turnover, through MMPs
      downregulation, which could contribute to the toxic effects observed in prostatic
      and testicular tissue after its exposure.

PMID- 25600810
TI  - General order parameter based correlation analysis of protein backbone motions
      between experimental NMR relaxation measurements and molecular dynamics
      simulations.
AB  - Internal backbone dynamic motions are essential for different protein functions
      and occur on a wide range of time scales, from femtoseconds to seconds. Molecular
      dynamic (MD) simulations and nuclear magnetic resonance (NMR) spin relaxation
      measurements are valuable tools to gain access to fast (nanosecond) internal
      motions. However, there exist few reports on correlation analysis between MD and
      NMR relaxation data. Here, backbone relaxation measurements of (15)N-labeled SH3
      (Src homology 3) domain proteins in aqueous buffer were used to generate general
      order parameters (S(2)) using a model-free approach. Simultaneously, 80 ns MD
      simulations of SH3 domain proteins in a defined hydrated box at neutral pH were
      conducted and the general order parameters (S(2)) were derived from the MD
      trajectory. Correlation analysis using the Gromos force field indicated that S(2)
      values from NMR relaxation measurements and MD simulations were significantly
      different. MD simulations were performed on models with different charge states
      for three histidine residues, and with different water models, which were SPC
      (simple point charge) water model and SPC/E (extended simple point charge) water
      model. S(2) parameters from MD simulations with charges for all three histidines
      and with the SPC/E water model correlated well with S(2) calculated from the
      experimental NMR relaxation measurements, in a site-specific manner. 

PMID- 25600811
TI  - Sir2 links the unfolded protein response and the heat shock response in a stress
      response network.
AB  - The Heat Shock Response (HSR) in the cytosol and the Unfolded Protein Response
      (UPR) in the endoplasmic reticulum are major pathways of the cellular
      proteostasis network. In Saccharomyces cerevisiae, HSR is regulated by
      transcription factor Hsf1, and UPR Ire1 branch activates transcription factor
      Hac1. Here we demonstrate systemic regulation of proteostasis through a direct
      link between UPR and HSR. Hsf1 is activated by UPR and its HSR depends on intact
      UPR. This link is mediated by Sir2, which is not only essential for Hsf1 HSR but
      also required for Hsf1 activation by UPR. Excess Sir2 augments Hsf1 activation by
      UPR and can compensate for its impairment in UPR-defective strains. Sir2 is
      upregulated by UPR but, in turn, it also attenuates this pathway, ensuring that
      UPR functions only transiently. 

PMID- 25600812
TI  - Biochemical and molecular characterization of novel mutations in GLB1 and NEU1 in
      patient cells with lysosomal storage disorders.
AB  - Lysosomes are cytoplasmic compartments that contain many acid hydrolases and play
      critical roles in the metabolism of a wide range of macromolecules. Deficiencies
      in lysosomal enzyme activities cause genetic diseases, called lysosomal storage
      disorders (LSDs). Many mutations have been identified in the genes responsible
      for LSDs, and the identification of mutations is required for the accurate
      molecular diagnoses. Here, we analyzed cell lines that were derived from two
      different LSDs, GM1 gangliosidosis and sialidosis. GM1 gangliosidosis is caused
      by mutations in the GLB1 gene that encodes beta-galactosidase. A lack of beta
      galactosidase activity leads to the massive accumulation of GM1 ganglioside,
      which results in neurodegenerative pathology. Mutations in the NEU1 gene that
      encodes lysosomal sialidase cause sialidosis. Insufficient activity of lysosomal
      sialidase progressively increases the accumulation of sialylated molecules, and
      various clinical symptoms, including mental retardation, appear. We sequenced the
      entire coding regions of GLB1 and NEU1 in GM1 gangliosidosis and sialidosis
      patient cells, respectively. We found the novel mutations p.E186A in GLB1 and
      p.R347Q in NEU1, as well as many other mutations that have been previously
      reported. We also demonstrated that patient cells containing the novel mutations
      showed the molecular phenotypes of the corresponding disease. Further structural
      analysis suggested that these novel mutation sites are highly conserved and
      important for enzyme activity. 

PMID- 25600813
TI  - Adipocytokine, omentin inhibits doxorubicin-induced H9c2 cardiomyoblasts
      apoptosis through the inhibition of mitochondrial reactive oxygen species.
AB  - Omentin is a relatively novel adipocyte-derived cytokine mainly expressed in
      visceral adipose tissues. Blood omentin level decreases in the patients with
      obesity, hypertension, type 2 diabetes and atherosclerosis. We have previously
      demonstrated that omentin inhibits key pathological processes for hypertension
      development, including vascular inflammatory responses, contractile reactivity
      and structural remodeling. In addition, there are several reports demonstrating
      that omentin prevents cardiac hypertrophy and myocardial ischemic injury.
      Doxorubicin (DOX) is an effective anti-cancer drug with cardiotoxic side effect.
      Here we tested the hypothesis that omentin may prevent DOX-induced cardiac
      cytotoxicity. H9c2 rat cardiomyoblasts were treated with DOX in the absence or
      presence of omentin. Omentin (300 ng/ml, 3 h pretreatment) significantly
      inhibited DOX (1 MUM, 18 h)-induced decreases in living cell number as determined
      by a colorimetric cell counting assay. Omentin (300 ng/ml, 3 h) significantly
      inhibited DOX (1 MUM, 12 h)-induced cleaved caspase-3 expression as determined by
      Western blotting. Omentin (300 ng/ml, 3 h) significantly inhibited DOX (1 MUM, 6
      h)-induced mitochondrial reactive oxygen species (ROS) production as determined
      by a MitoSOX Red fluorescent staining. In addition, a mitochondrial respiratory
      chain complex I inhibitor, rotenone (0.5 MUM, 3 h pretreatment), significantly
      inhibited DOX (1 MUM, 6-18 h)-induced decreases of living cell number, cleaved
      caspase-3 expression and mitochondrial ROS production. In summary, we for the
      first time demonstrate that omentin prevents DOX-induced H9c2 cells apoptosis
      through the inhibition of mitochondrial ROS production. These results indicate
      omentin as an attractive pharmaco-therapeautic target against DOX-induced cardiac
      side effect.

PMID- 25600814
TI  - Mechanism of 1-Cys type methionine sulfoxide reductase A regeneration by
      glutaredoxin.
AB  - Glutaredoxin (Grx), a major redox regulator, can act as a reductant of methionine
      sulfoxide reductase A (MsrA). However, the biochemical mechanisms involved in
      MsrA activity regeneration by Grx remain largely unknown. In this study, we
      investigated the regeneration mechanism of 1-Cys type Clostridium oremlandii MsrA
      (cMsrA) lacking a resolving Cys residue in a Grx-dependent assay. Kinetic
      analysis showed that cMsrA could be reduced by both monothiol and dithiol Grxs as
      efficiently as by in vitro reductant dithiothreitol. Our data revealed that the
      catalytic Cys sulfenic acid intermediate is not glutathionylated in the presence
      of the substrate, and that Grx instead directly formed a complex with cMsrA. Mass
      spectrometry analysis identified a disulfide bond between the N-terminal
      catalytic Cys of the active site of Grx and the catalytic Cys of cMsrA. This
      mixed disulfide bond could be resolved by glutathione. Based on these findings,
      we propose a model for regeneration of 1-Cys type cMsrA by Grx that involves no
      glutathionylation on the catalytic Cys of cMsrA. This mechanism contrasts with
      that of the previously known 1-Cys type MsrB.

PMID- 25600815
TI  - Smartphone applications for melanoma detection by community, patient and
      generalist clinician users: a review.
AB  - Smartphone health applications ('apps') are widely available but experts remain
      cautious about their utility and safety. We reviewed currently available apps for
      the detection of melanoma (July 2014), aimed at general community, patient and
      generalist clinician users. A proforma was used to extract and assess each app
      that met the inclusion criteria, and we undertook content analysis to evaluate
      their content and the evidence applied in their development. Thirty-nine apps
      were identified with the majority available only for Apple users. Over half (n =
      22) provided information or education about melanoma, ultraviolet radiation
      exposure prevention advice, and skin self-examination strategies, mainly using
      the ABCDE (A, Asymmetry; B, Border; C, Colour; D, Diameter; E, Evolving) method.
      Half (n = 19) helped users take and store images of their skin lesions either for
      review by a dermatologist or for self-monitoring to identify change, an important
      predictor of melanoma; a similar number (n = 18) used reminders to help users
      monitor their skin lesions. A few (n = 9) offered expert review of images. Four
      apps provided a risk assessment to patients about the probability that a lesion
      was malignant or benign, and one app calculated users' future risk of melanoma.
      None of the apps appeared to have been validated for diagnostic accuracy or
      utility using established research methods. Smartphone apps for detecting
      melanoma by nonspecialist users have a range of functions including information,
      education, classification, risk assessment and monitoring change. Despite their
      potential usefulness, and while clinicians may choose to use apps that provide
      information to educate their patients, apps for melanoma detection require
      further validation of their utility and safety. 

PMID- 25600816
TI  - A cutaneous positioning system.
AB  - Our previous work revealed that torso cutaneous information contributes to the
      internal representation of the torso and plays a role in postural control. Hence,
      the aims of this study were to assess whether posture could be manipulated by
      patterns of vibrotactile stimulation and to determine whether resulting modified
      postures were associated with specific and consistent spatial attitudes. Ten
      healthy young adults stood in normal and Romberg stances with six vibrating
      actuators positioned on the torso in contact with the skin over the anatomical
      locations corresponding to left and right external oblique, internal oblique and
      erector spinae muscles at the L4/L5 vertebrae level. A 250-Hz tactile vibration
      was applied for 5 s either at a single location or consecutively at each location
      in clockwise or counterclockwise sequences. Kinematic analysis of the body
      segments indicated that postural responses observed in response to single and
      sequential stimulation patterns were similar, while the center of pressure
      remained unaltered in any situations. Moreover, torso inclinations followed
      rectilinear-like path segments chartered by stimuli loci during sequential
      stimulations. Comparison of torso attitudes with previous results obtained with
      co-vibration patterns of the same duration showed that torso inclination
      amplitudes are equivalent for single (one location) and co-vibration (pairs of
      locations) patterns inducing the same directional effect. Hence, torso cutaneous
      information exhibits kinesthetic properties, appears to provide a map of upper
      body spatial configuration, and could assume the role of an internal positioning
      system for the upper body.

PMID- 25600817
TI  - No effect of delay on the spatial representation of serial reach targets.
AB  - When reaching for remembered target locations, it has been argued that the brain
      primarily relies on egocentric metrics and especially target position relative to
      gaze when reaches are immediate, but that the visuo-motor system relies stronger
      on allocentric (i.e., object-centered) metrics when a reach is delayed. However,
      previous reports from our group have shown that reaches to single remembered
      targets are represented relative to gaze, even when static visual landmarks are
      available and reaches are delayed by up to 12 s. Based on previous findings which
      showed a stronger contribution of allocentric coding in serial reach planning,
      the present study aimed to determine whether delay influences the use of a gaze
      dependent reference frame when reaching to two remembered targets in a sequence
      after a delay of 0, 5 or 12 s. Gaze was varied relative to the first and second
      target and shifted away from the target before each reach. We found that
      participants used egocentric and allocentric reference frames in combination with
      a stronger reliance on allocentric information regardless of whether reaches were
      executed immediately or after a delay. Our results suggest that the relative
      contributions of egocentric and allocentric reference frames for spatial coding
      and updating of sequential reach targets do not change with a memory delay
      between target presentation and reaching.

PMID- 25600818
TI  - Transcranial direct current stimulation can selectively affect different
      processing channels in human visual cortex.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive brain
      stimulation technique that can modulate cortical activity. Nonetheless,
      information regarding its functional specificity and the extent by which visual
      performance can be modulated is still lacking. Here, we used vision as model to
      address if it differentially affects different cell groups in the stimulated
      area. We applied tDCS to the occiput and performed a series of visual tests in a
      sham-controlled repeated-measures design. Achromatic contrast sensitivity was
      assessed psychophysically during tDCS, with tasks designed to target specific
      spatial frequency (SF) channels, inferred ON, OFF channels and inferred
      magnocellular and parvocellular pathways of the visual system. Sweep visual
      evoked potential (sVEP) for contrast sensitivity and Vernier acuity was recorded
      before and after tDCS. Anodal tDCS significantly increased thresholds for
      luminance decrements (OFF) only for the inferred magnocellular thresholds.
      Although tDCS had no significant effects on Vernier or contrast sVEP thresholds,
      it modulated suprathreshold amplitudes for both tasks. Cathodal tDCS increased
      sVEP amplitudes at a low SF, decreased it at a medium, and had no effect at a
      high SF. Cathodal tDCS increased sVEP phase lags for low and decreased it for
      high SF (maximum change corresponding to change in apparent latency >6 ms).
      Cathodal and anodal stimulation decreased amplitudes of sVEP Vernier responses.
      Exclusive tDCS effects on magnocellular thresholds agree with reports of pathway
      specific tDCS effects. The dependence of tDCS effects on SF and contrast levels
      further suggests that tDCS differentially affects different cell groups in the
      visual cortex.

PMID- 25600819
TI  - Peripheral nerve injury activates convergent nociceptive input to dorsal horn
      neurons from neighboring intact nerve.
AB  - Previous studies demonstrated that peripheral nerve injury induced excessive
      nociceptive response of spinal cord dorsal horn neurons and such change has been
      proposed to reflect the development of neuropathic pain state. The aim of this
      study was to examine the spinal dorsal horn for convergence of nociceptive input
      to second-order neurons deafferented by peripheral nerve injury. Double
      immunofluorescence labeling for c-Fos and phosphorylated extracellular signal
      regulated kinase (p-ERK) was performed to detect convergent synaptic input to
      spinal dorsal horn neurons after the saphenous nerve injury. c-Fos expression and
      the phosphorylation of ERK were induced by noxious heat stimulation of the
      hindpaw and by electrical stimulation of the injured or uninjured saphenous
      nerve, respectively. Within the central terminal field of the saphenous nerve,
      the number of c-Fos protein-like immunoreactive (c-Fos-IR) cell profiles was
      significantly decreased at 3 days and returned to the control level by 14 days
      after the injury. p-ERK immunoreactive (p-ERK-IR) cell profiles were distributed
      in the central terminal field of the saphenous nerve, and the topographic
      distribution pattern and number of such p-ERK-IR cell profiles remained unchanged
      after the nerve injury. The time course of changes in the number of double
      labeled cell profiles was similar to that of c-Fos-IR cell profiles after the
      injury. These results indicate that convergent primary nociceptive input through
      neighboring intact nerves contributes to increased responsiveness of spinal
      dorsal horn nociceptive neurons.

PMID- 25600820
TI  - Performance Evaluation of a Salivary Amylase Biosensor for Stress Assessment in
      Military Field Research.
AB  - BACKGROUND: A convenient biosensor for real-time measurement of biomarkers for in
      field psychophysiological stress research and military operations is desirable.
      We evaluated a hand-held device for measuring salivary amylase as a stress marker
      in medical technicians undergoing combat casualty care training using two
      different modalities in operating room and field settings. METHODS: Salivary
      amylase activity was measured by two biosensor methods: directly sampling saliva
      with a test strip placed under the tongue or pipetting a fixed volume of
      precollected saliva onto the test strip, followed by analyzing the sample on the
      strip using a biosensor. The two methods were compared for their accuracy and
      sensitivity to detect the stress response using an enzyme assay method as a
      standard. RESULTS: The measurements from the under-the-tongue method were not as
      consistent with those from the standard assay method as the values obtained from
      the pipetting method. The under-the-tongue method did not detect any significant
      increase in the amylase activity due to stress in the operating room (P > 0.1),
      in contrast to the significant increases observed using the pipetting method and
      assay method with a significance level less than 0.05 and 0.1, respectively.
      Furthermore, the under-the-tongue method showed no increased amylase activity in
      the field testing, while both the pipetting method and assay method showed
      increased amylase activity in the same group (P < 0.1). CONCLUSION: The accuracy
      and consistency of the biosensors need to be improved when used to directly
      measure salivary amylase activity under the tongue for stress assessment in
      military medical training.

PMID- 25600821
TI  - Digested wheat gluten inhibits binding between leptin and its receptor.
AB  - BACKGROUND: Leptin resistance is considered a primary risk factor for obesity. It
      has been hypothesized that dietary cereal grain protein could cause leptin
      resistance by preventing leptin from binding to its receptor. Non-degraded
      dietary wheat protein has been found in human serum at a mean level of 41 ng/mL.
      Here, we report our findings from testing whether enzymatically digested gluten
      from wheat prevents leptin from binding to the leptin receptor in vitro. Gluten
      from wheat was digested with pepsin and trypsin under physiological conditions.
      Pepsin and trypsin activity was removed from the gluten digest with a 10 kDa spin
      filter or by heat treatment at 100 degrees C for 30 min. Binding to the leptin
      receptor of leptin mixed with gluten digest at a series of concentrations was
      measured using surface plasmon resonance technology. RESULTS: Binding of the
      gluten digest to the leptin receptor was not detected. Spin-filtered gluten
      digest inhibited binding of leptin to the leptin receptor, with 50% inhibition at
      a gluten digest concentration of ~10 ng/mL. Heat-treated gluten digest did not
      inhibit leptin binding. CONCLUSIONS: Digested wheat gluten inhibits binding of
      leptin to the leptin receptor, with half-maximal inhibition at 10 ng/mL. The
      inhibition is significant at clinically relevant concentrations and could
      therefore serve as a novel pathway to investigate to understand the molecular
      basis of leptin resistance, obesity and associated disorders.

PMID- 25600822
TI  - Glutamatergic and neurometabolic alterations in chronic cocaine users measured
      with (1) H-magnetic resonance spectroscopy.
AB  - Cocaine addiction is a chronically relapsing disorder that is associated with
      harmful consequences. Relapses occur frequently and effective pharmacotherapies
      are currently sparse. Preclinical studies suggest that altered glutamatergic
      signaling is crucial for the maintenance of cocaine self-administration. However,
      the translational validity of these models is currently unknown. Therefore, we
      investigated potential differences of glutamate, glutamine and further metabolite
      levels in the pregenual anterior cingulate cortex (pgACC) and the right
      dorsolateral prefrontal cortex (rDLPFC) of chronic cocaine users and controls
      using the PRior knOwledge FITting 2.0 tool in combination with two-dimensional J
      resolved single-voxel (1) H-magnetic resonance spectroscopy at 3T and voxel
      tissue composition and relaxation correction. Glutamate and glutamine levels did
      not differ between cocaine users and controls, but higher weekly cocaine use and
      higher cocaine hair concentrations were associated with lower glutamine/creatine
      ratios in the pgACC. Interestingly, cocaine users exhibited higher glucose/total
      creatine ratios than controls in the pgACC and higher choline/creatine ratios in
      the pgACC and rDLPFC. These results imply that cocaine use is associated with
      altered cortical glucose metabolism and membrane turnover. Finally, cocaine use
      over the past 6 months appears to decrease cortical glutamine levels indicating
      changes in glutamate cycling. 

PMID- 25600823
TI  - Femtosecond all-optical synchronization of an X-ray free-electron laser.
AB  - Many advanced applications of X-ray free-electron lasers require pulse durations
      and time resolutions of only a few femtoseconds. To generate these pulses and to
      apply them in time-resolved experiments, synchronization techniques that can
      simultaneously lock all independent components, including all accelerator modules
      and all external optical lasers, to better than the delivered free-electron laser
      pulse duration, are needed. Here we achieve all-optical synchronization at the
      soft X-ray free-electron laser FLASH and demonstrate facility-wide timing to
      better than 30 fs r.m.s. for 90 fs X-ray photon pulses. Crucially, our analysis
      indicates that the performance of this optical synchronization is limited
      primarily by the free-electron laser pulse duration, and should naturally scale
      to the sub-10 femtosecond level with shorter X-ray pulses. 

PMID- 25600824
TI  - Quantitative analysis for in situ sintering of 3% yttria-stablized zirconia in
      the transmission electron microscope.
AB  - Studying particle-agglomerate systems compared to two-particle systems elucidates
      different stages of sintering by monitoring both pores and particles. We report
      on in situ sintering of 3% yttria-stablized zirconia particle agglomerates in the
      transmission electron microscope (TEM). Real-time TEM observations indicate neck
      formation and growth, particle coalescence and pore closure. A MATLAB-based image
      processing tool was developed to calculate the projected area of the agglomerate
      with and without internal pores during in situ sintering. We demonstrate the
      first densification curves generated from sequentially acquired TEM images. The
      in situ sintering onset temperature was then determined to be at 960  degrees C.
      Densification curves illustrated that the agglomerate projected area which
      excludes the internal observed pores also shrinks during in situ sintering. To
      overcome the common projection problem for TEM analyses, agglomerate mass
      thickness maps were obtained from low energy-loss analysis combined with STEM
      imaging. The decrease in the projected area was directly related to the increase
      in mass-thickness of the agglomerate, likely caused by hidden pores existing in
      the direction of the beam. Access to shrinkage curves through in situ TEM
      analysis provides a new avenue to investigate fundamental mechanisms of sintering
      through directly correlating microstructural changes during consolidation with
      mesoscale densification behavior.

PMID- 25600826
TI  - Can masticatory electromyography be normalised to submaximal bite force?
AB  - The combination of bite force and jaw muscle electromyography (EMG) provides an
      insight into the performance of the stomatognathic system, especially in relation
      to dynamic movement tasks. Literature has extensively investigated possible
      methods for normalising EMG data encapsulating many different approaches.
      However, bite force literature trends towards normalising EMG to a maximal
      voluntary contraction (MVC), which could be difficult for ageing populations or
      those with poor dental health or limiting conditions such as temporomandibular
      disorder. The objectives of this study were to (i) determine whether jaw-closing
      muscle activity is linearly correlated with incremental submaximal and maximal
      bite force levels and (ii) assess whether normalising maximal and submaximal
      muscle activity to that produced when performing a low submaximal bite force (20
      N) improves repeatability of EMG values. Thirty healthy adults (15 men, 15 women;
      mean age 21 +/- 1.2 years) had bite force measurements obtained using a custom
      made button strain gauge load cell. Masseter and anterior temporalis muscle
      activities were collected bilaterally using surface EMG sensors whilst
      participants performed maximal biting and three levels of submaximal biting.
      Furthermore, a small group (n = 4 females) were retested for reliability
      purposes. Coefficients of variation and intra-class correlation coefficients
      showed markedly improved reliability when EMG data were normalised compared to
      non-normalised. This study shows that jaw muscle EMG may be successfully
      normalised to a very low bite force. This may open possibilities for comparisons
      between at-risk sample groups that may otherwise find it difficult to produce
      maximal bite force values.

PMID- 25600825
TI  - Optimizing detector geometry for trace element mapping by X-ray fluorescence.
AB  - Trace metals play critical roles in a variety of systems, ranging from cells to
      photovoltaics. X-Ray Fluorescence (XRF) microscopy using X-ray excitation
      provides one of the highest sensitivities available for imaging the distribution
      of trace metals at sub-100 nm resolution. With the growing availability and
      increasing performance of synchrotron light source based instruments and X-ray
      nanofocusing optics, and with improvements in energy-dispersive XRF detectors,
      what are the factors that limit trace element detectability? To address this
      question, we describe an analytical model for the total signal incident on XRF
      detectors with various geometries, including the spectral response of energy
      dispersive detectors. This model agrees well with experimentally recorded X-ray
      fluorescence spectra, and involves much shorter calculation times than with Monte
      Carlo simulations. With such a model, one can estimate the signal when a trace
      element is illuminated with an X-ray beam, and when just the surrounding non
      fluorescent material is illuminated. From this signal difference, a contrast
      parameter can be calculated and this can in turn be used to calculate the signal
      to-noise ratio (S/N) for detecting a certain elemental concentration. We apply
      this model to the detection of trace amounts of zinc in biological materials, and
      to the detection of small quantities of arsenic in semiconductors. We conclude
      that increased detector collection solid angle is (nearly) always advantageous
      even when considering the scattered signal. However, given the choice between a
      smaller detector at 90 degrees  to the beam versus a larger detector at 180
      degrees  (in a backscatter-like geometry), the 90 degrees  detector is better for
      trace element detection in thick samples, while the larger detector in 180
      degrees  geometry is better suited to trace element detection in thin samples. 

PMID- 25600827
TI  - Cellularity, characteristics of hematopoietic parameters and prognosis in
      myelodysplastic syndromes.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) present with a normo- or hyperplastic
      bone marrow in most cases. We aimed at a characterization of patients with
      different types of cellularity. METHODS: We assessed marrow cellularity both by
      histology and cytology in 1270 patients and analyzed hematologic, cytogenetic,
      and prognostic parameters accordingly. RESULTS: The concordance of the assessment
      of cellularity differed dramatically between histology and cytology as only 36.5%
      were described as hypocellular by both methods (P < 0.0005) (hypocellular 16.4%,
      normocellular 23.3%, hypercellular 60.3%). There were no major differences with
      regard to hematopoietic insufficiency. The presence of fibrosis was associated to
      hypercellular bone marrow. Median survival differed from 38 months in
      hypocellular, 42 months in normocellular, and 25 months in hypercellular MDS (P <
      0.0005). AML progression rates were 33% for hypercellular MDS after 2 yr, whereas
      hypo- and normocellular had a progression rate of 19% after 2 yr (P = 0.018).
      IPSS and IPSS-R were able to identify different risk groups within all three
      cellularity groups. CONCLUSION: Based on our data, hypocellular patients
      obviously do not present as a separate entity, as there were no striking
      differences with regard to cytogenetics and WHO types. Assessment of cellularity
      should be performed by histopathology.

PMID- 25600828
TI  - Etanercept for patients with psoriasis who did not respond or who lost their
      response to adalimumab or infliximab.
AB  - BACKGROUND: There is a paucity of data on the use of etanercept in patients who
      have previously failed a different tumour necrosis factor (TNF) alpha antagonist.
      OBJECTIVES: To study etanercept in patients who did not achieve a satisfactory
      response to adalimumab or who lost their response to adalimumab or infliximab and
      to explore the role of anti-adalimumab and anti-infliximab antibodies in
      etanercept response. METHODS: Patients with psoriasis who did not achieve a
      satisfactory response to adalimumab or who lost their response to adalimumab or
      infliximab were included. All patients received etanercept 50 mg twice a week for
      12 weeks followed by 50 mg once a week for 12 more weeks. Anti-infliximab and
      anti-adalimumab antibodies were measured at baseline. The primary objective was
      to study the efficacy of etanercept using the proportion of patients who achieved
      a physician global assessment (PGA) of 0 or 1. RESULTS: A total of 81 patients
      were included. The proportion of patients who achieved a PGA of 0 or 1 after 24
      weeks of etanercept was 20.0% (95% CI 4.8-35.2%) for patients who had an
      unsatisfactory response to adalimumab, 35.1% (95% CI 19.0-51.3%) and 35.7% (95%
      CI 7.0-64.4%) for patients who lost their response to adalimumab and infliximab
      respectively. The proportion of patients who achieved a PGA of 0 or 1 at week 24
      was numerically higher for patients who had anti-adalimumab or anti-infliximab
      antibodies (36.5%) as compared to those without (17.2%; P = 0.08). CONCLUSIONS:
      Etanercept can be effective in patients with psoriasis who failed a previous TNF
      alpha antagonist.

PMID- 25600829
TI  - Equality, accessibility, and availability of physical therapy services in Israel
      Perception of national directors.
AB  - To date no research has described Israeli physical therapy (PT) services to
      determine whether they are provided in the spirit intended by the National Health
      Insurance Law (NHIL). This study aimed to assess the equality, accessibility, and
      availability of PT services in Israel. Qualitative research was based on semi
      structured, personal interviews with all national directors of PT services in
      Israel, followed by content analysis of the data obtained. According to the
      findings, PT services are provided by all Health Maintenance Organisations (HMOs)
      throughout Israel. In peripheral areas, access to services is limited;
      availability of services at most clinics is poor, a problem which is solved
      mainly by referring patients to PT outsourcing. The number of treatment sessions
      is determined by the NHIL; however, all directors agreed that the number of
      treatments provided should be based on a professional decision following patient
      evaluation and progress, rather than on administrative considerations. Inequality
      of service to peripheral areas could be reduced by creating cooperation between
      HMOs, thereby establishing clinics capable of providing services that are both
      accessible and equitable. In addition, the number of sessions provided to
      patients in the health-care basket should be reassessed, and a set of uniform
      criteria should be created for determining the optimal number of PT sessions.
      This could lead to greater uniformity in distribution of PT services provided by
      the HMOs. 

PMID- 25600830
TI  - High performance organic-inorganic perovskite-optocoupler based on low-voltage
      and fast response perovskite compound photodetector.
AB  - Organic-inorganic hybrid photodetectors attract considerable attention because
      they can combine the advantages of both organic and inorganic systems. Here, a
      perovskite compound with a broad absorption spectrum and high power conversion
      efficiency is used as a photosensitive layer in an organic/inorganic hybrid
      heterojunction photodetector with a high and fast response. The high sensitivity
      exceeding 10(4) is obtained at bias of 0-4 V. Using a tandem organic light
      emitting diode (OLED) as the light source, we fabricated an optocoupler device.
      The optocoupler achieved a maximum photoresponsivity of 1.0 A W(-1) at 341.3
      MUWcm(-2) at an input voltage of 6 V. The device also exhibits rapid response
      times of tau(rise) ~ 20 MUs and tau(fall) ~ 17 MUs; as well as a high current
      transfer ratio (CTR) of 28.2%. After applying an amplification circuit, the CTR
      of the optocoupler increases to 263.3%, which is comparable with that of
      commercial inorganic optocouplers. The developed hybrid optocoupler thus shows
      great promise for use in photonics.

PMID- 25600831
TI  - Microwave-assisted synthesis of the anticancer drug cisplatin, cis-[Pt(NH3)2Cl2].
AB  - A microwave-assisted synthesis of cisplatin, cis-[Pt(NH3)2Cl2], has been
      developed and optimized on both a 0.2 and 0.05 millimolar scale. The optimized
      synthetic procedure was modeled after the Lebedinskii-Golovnya method and is
      suitable for incorporating the radionuclide, (195m)Pt, into cisplatin for
      biological studies. Highest yields (47%) and purity are obtained using a K2PtCl4
      : NH4OAc : KCl molar ratio of 1 : 4 : 2 at a temperature of 100  degrees C. The
      entire synthesis and purification procedure requires approximately 80 min. At a
      reaction temperature of 150  degrees C, the trans isomer is the exclusive
      product, suggesting that complexes of the general form, trans-[Pt(RNH2)2Cl2], can
      be synthesized directly from K2PtCl4 using [RNH3]OAc (R = alkyl or aryl moieties)
      via a microwave process. Two novel separation procedures have been developed
      which efficiently remove the major impurity (1 : 1 Magnus-type salt) from the
      crude reaction product, yielding a product of purity comparable to that obtained
      by the Dhara method and suitable for biological studies. These procedures are
      applicable to both the micro- and macro-scale of synthesis. The question of
      whether this microwave-assisted synthesis of cisplatin will be a preferred method
      for incorporating (195m)Pt into cisplatin is yet to be determined. 

PMID- 25600832
TI  - Bangkit: The Processes of Recovery from First Episode Psychosis in Java.
AB  - There is a growing literature on recovery from schizophrenia. Most studies,
      however, focused on outcome, with insufficient attention paid to the process of
      recovery. The aim of this study was to explore the process of recovery from first
      episode psychotic illness in a Javanese cultural setting. An ethnographic method
      was applied where researcher conducted a field work and followed seven
      participants in their natural setting. This study identified three phases of
      recovery process in the context of Javanese culture: Bangkit, gaining insight;
      Usaha, struggling to achieve recovery; and Rukun, harmonious integration with
      family and community integration. Recovery entails regaining insight, followed by
      simultaneous inward and outward efforts that reconstitute one's inner and outer
      world, respectively. Participants also expressed their recovery in terms of a
      movement through physical space, from confinement in their own home to the wider
      spaces shared with family and community. Movements in physical space parallel
      movements in social space, where participants accomplish a social recovery. The
      Javanese phase of recovery found in this study is comparable to the phase of
      recovery identified by previous literatures in the Western context. 

PMID- 25600833
TI  - Bcl-2-associated athanogene 2 prevents the neurotoxicity of MPP+ via interaction
      with DJ-1.
AB  - Bcl-2-associated athanogene 2 (BAG2) is an important member in the BAG family
      which is characterized by their property of interaction with a variety of
      partners involved in modulating the proliferation/death balance. The role of BAG
      family proteins in Parkinson's disease (PD) has not been elucidated. In this
      study, we demonstrated that overexpressing BAG2 ameliorates the effects of 1
      methyl-4-phenylpyridinium (MPP+) in mitochondrial membrane potential (MMP)
      collapse, reactive oxygen species (ROS) generation, and mitochondrial release of
      cytochrome C. However, knockdown of DJ-1 abolished the neuroprotective effects of
      BAG2 against MPP+-induced neuronal toxicity. With co-immunoprecipitation and
      pulldown experiments, we present a direct physical interaction between BAG2 and
      DJ-1. Co-expression of BAG-2 together with DJ-1 increased the ratio of
      dimer/monomer staining intensity at the basal level. Our results indicated that
      MPP+ treatment leads to the disassociation of the homodimer of DJ-1. When BAG2
      was overexpressed in cells, the homodimer of DJ-1 was increased. Importantly,
      BAG2 prevents MPP+-induced monomerization of DJ-1. Thus, our data showed that the
      neuroprotective effects of BAG2 are mediated by its interaction with DJ-1,
      strengthening the link between the BAG proteins and PD-related neurodegeneration.

PMID- 25600834
TI  - MS risk allele rs1883832T is associated with decreased mRNA expression of CD40.
AB  - CD40-CD40L interactions mediate T-dependent B cell response and efficient T cell
      priming. Therefore, genes encoding these molecules are attractive candidates for
      studies on autoimmune diseases, such as multiple sclerosis (MS), in which
      activated T and B cells are involved. Thus, we analyzed CD40 and CD40L mRNA
      expression in whole blood samples from MS patients and controls. Additionally, we
      examined the effect of three SNPs of CD40 (rs1883832C>T, rs11569343C>G, and
      rs752118C>T) and two SNPs of CD40L (rs3092923T>C and rs3092952A>G) on their mRNA
      expression. Our results showed that the rs1883832C>T SNP affects CD40 gene
      expression. Our analysis revealed that individuals possessing CT and TT genotypes
      (predisposing to MS) had decreased level of CD40 mRNA in comparison to those with
      CC. Moreover, we demonstrated the potential role of impaired CD40-CD40L
      interaction in developing of multiple sclerosis.

PMID- 25600836
TI  - Integration of transcriptomics and metabolomics data specifies the metabolic
      response of Chlamydomonas to rapamycin treatment.
AB  - Flux phenotypes predicted by constraint-based methods can be refined by the
      inclusion of heterogeneous data. While recent advances facilitate the integration
      of transcriptomics and proteomics data, purely stoichiometry-based approaches for
      the prediction of flux phenotypes by considering metabolomics data are lacking.
      Here we propose a constraint-based method, termed TREM-Flux, for integrating time
      resolved metabolomics and transcriptomics data. We demonstrate the applicability
      of TREM-Flux in the dissection of the metabolic response of Chlamydomonas
      reinhardtii to rapamycin treatment by integrating the expression levels of 982
      genes and the content of 45 metabolites obtained from two growth conditions. The
      findings pinpoint cysteine and methionine metabolism to be most affected by the
      rapamycin treatment. Our study shows that the integration of time-resolved
      unlabeled metabolomics data in addition to transcriptomics data can specify the
      metabolic pathways involved in the system's response to a studied treatment. 

PMID- 25600835
TI  - GRP75 Involves in Retinal Ganglion Cell Apoptosis After Rat Optic Nerve Crush.
AB  - Glucose-regulated protein 75 (GRP75), a member of the heat-shock protein 70
      family, is known to protect cells from stress-induced injury. However,
      information regarding its distribution and possible function in the retina is
      limited. In this study, we performed an optic nerve crush (ONC) model in adult
      rats and found that GRP75 was significantly upregulated in the retina after ONC.
      Double immunofluorescent staining revealed that GRP75 was localized in the
      retinal ganglion cells (RGCs). We also examined the expression profile of active
      caspase3, whose change was correlated with the expression profile of GRP75. In
      addition, we utilized co-staining of GRP75 and active caspase3 and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to study their
      correlation in the retina following ONC. Furthermore, the expressions of Bax,
      cytochrome c (Cytc), p-extracellular-signal-regulated kinases (ERK)1/2, and p-AKT
      were enhanced in the retina after ONC, and they were parallel with the expression
      profile of GRP75. Based on our data, we speculated that GRP75 might play an
      important role in RGCs apoptosis following ONC. 

PMID- 25600837
TI  - Snakes as hazards: modelling risk by chasing chimpanzees.
AB  - Snakes are presumed to be hazards to primates, including humans, by the snake
      detection hypothesis (Isbell in J Hum Evol 51:1-35, 2006; Isbell, The fruit, the
      tree, and the serpent. Why we see so well, 2009). Quantitative, systematic data
      to test this idea are lacking for the behavioural ecology of living great apes
      and human foragers. An alternative proxy is snakes encountered by primatologists
      seeking, tracking, and observing wild chimpanzees. We present 4 years of such
      data from Mt. Assirik, Senegal. We encountered 14 species of snakes a total of
      142 times. Almost two-thirds of encounters were with venomous snakes. Encounters
      occurred most often in forest and least often in grassland, and more often in the
      dry season. The hypothesis seems to be supported, if frequency of encounter
      reflects selective risk of morbidity or mortality.

PMID- 25600838
TI  - Economic burden of chemotherapy-induced febrile neutropenia in patients with
      lymphoma: a systematic review.
AB  - The primary objective of this review was to identify the cost components that
      were most frequently associated with the economic burden of febrile neutropenia
      (FN) among patients with lymphoma. The secondary objective was to identify any
      parameter associated with higher FN cost. Ten cost of illness (COI) studies were
      identified. General characteristics on study design, country, perspective, and
      patient population were extracted and systematically reported. It was observed
      that majority (70%) of the studies employed the perspective of healthcare
      provider. 20% of the studies considered long-term costs. Estimated costs were
      adjusted to 2013 US dollars and ranged from US$5819 to US$34,756. The cost
      components that were most frequently associated with economic burden were ward
      and medication costs. Inpatient management, male gender, discharged dead, and
      comorbidity were positively associated with higher FN costs. Future COI studies
      on FN should focus on the accurate estimation on ward and medication costs. 

PMID- 25600839
TI  - New perspectives in the treatment of adult medulloblastoma in the era of
      molecular oncology.
AB  - Medulloblastoma is the most common central nervous system tumor in children,
      while it is extremely rare in adults. Multimodal treatment involving surgery,
      radiotherapy and chemotherapy can improve the prognosis of this disease, and
      recent advances in molecular biology have allowed the identification of molecular
      subgroups (WNT, SHH, Groups 3 and 4), each of which have different cytogenetic,
      mutational and gene expression signatures, demographics, histology and prognosis.
      The present review focuses on the state of the art for adult medulloblastoma
      treatment and on novel molecular advances and their future implications in the
      treatment of this disease. 

PMID- 25600840
TI  - Whole pelvic intensity-modulated radiotherapy for gynecological malignancies: A
      review of the literature.
AB  - Radiation therapy has long played a major role in the treatment of gynecological
      malignancies. There is increasing interest in the utility of intensity-modulated
      radiotherapy (IMRT) and its application to treat gynecological malignancies.
      Herein, we review the state-of-the-art use of IMRT for gynecological malignancies
      and report how it is being used alone as well as in combination with chemotherapy
      in both the adjuvant and definitive settings. Based on dosimetric and clinical
      evidence, IMRT can reduce gastrointestinal, genitourinary, and hematological
      toxicities compared with 3D-conformal radiotherapy for gynecologic malignancies.
      We discuss how these attributes of IMRT may lead to improvements in disease
      outcomes by allowing for dose escalation of radiation therapy, intensification of
      chemotherapy, and limiting toxicity-related treatment breaks. Currently accruing
      trials investigating pelvic IMRT for cervical and endometrial cancers are
      discussed. 

PMID- 25600841
TI  - Carbapenem susceptibility among Escherichia coli, Klebsiella pneumoniae, and
      Enterobacter cloacae isolates obtained from patients in intensive care units in
      Taiwan in 2005, 2007, and 2009.
AB  - To investigate the evolutionary trends in non-susceptibility of carbapenems
      against the isolates of Escherichia coli, Klebsiella pneumoniae, and Enterobacter
      cloacae from patients hospitalized in intensive care units (ICUs) of major
      teaching hospitals throughout Taiwan during 2005-2009, we applied the breakpoints
      of MICs recommended by Clinical and Laboratory Standards Institute and European
      Committee on Antimicrobial Susceptibility Testing in 2013. Escalations in
      imipenem MIC levels for overall E. coli and E. cloacae isolates and extended
      spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates were noted during
      this period. The overall MIC levels against imipenem and meropenem for subgroups
      of ESBL producers of 3 Enterobacteriaceae species were significantly higher than
      those of respective overall groups in 2007 and 2009. Compared with meropenem, we
      found that significant evidence of imipenem MIC creep and evidence of
      extraordinarily high rates of non-susceptibility to ertapenem among isolates of 3
      species in 2009 existed. The prominent rises in rates of ertapenem non
      susceptibility for ESBL-producing E. coli and K. pneumoniae during 2005-2009 and
      rate of ESBL positivity for E. cloacae between 4 years were notably found. Based
      on our findings, ertapenem should be used cautiously in management of the ICU
      infections caused by these potentially ESBL-producing Enterobacteriaceae isolates
      in Taiwan.

PMID- 25600842
TI  - In vitro activity of a Hos2 deacetylase inhibitor, MGCD290, in combination with
      echinocandins against echinocandin-resistant Candida species.
AB  - MGCD290, a Hos2 fungal histone deacetylase inhibitor, showed modest activity when
      tested alone (MIC range, 0.12-4 MUg/mL; MIC50/90, 0.5/4 MUg/mL) against Candida
      glabrata (n=15; 14 fks mutants; 5 also fluconazole resistant), Candida albicans
      (8 fks mutants; 2 also fluconazole resistant), Candida tropicalis (4 fks
      mutants), and Candida krusei (3 fks mutants). However, MGCD290 showed synergy or
      partial synergy for 33.3%, 30.1%, 36.7%, and 80.0% of the isolates when tested
      with anidulafungin, caspofungin, micafungin, and fluconazole, respectively.
      Favorable interactions were achieved with low concentrations of MGCD290 (0.015
      0.25 MUg/mL), and categorical shifts were observed in 2 of 8 (25.0%) isolates of
      C. albicans and 2 of 3 (66.7%) isolates of C. krusei and in 4 of the 5 (80.0%)
      fluconazole-resistant isolates of C. glabrata. MGCD290 exerts a distinctly
      favorable influence on the MICs of fluconazole and the echinocandins, resulting
      in conversion from resistance to susceptibility regardless of fks mutations.

PMID- 25600843
TI  - Detection of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates
      using a combination of delta-hemolysis assay and Etest.
AB  - This study evaluated the delta-hemolysis assay for detection of heterogeneous
      vancomycin-intermediate Staphylococcus aureus (hVISA) isolates. The assay was
      performed using Columbia or trypticase soy blood agar plates without vancomycin
      at 37 degrees C with 5% CO2, and the test isolate was streaked perpendicularly
      1mm away from S. aureus RN4220. One hundred thirty-eight methicillin-resistant S.
      aureus (MRSA) bloodstream isolates with vancomycin MICs of 0.75-2 MUg/mL were
      screened for hVISA by the delta-hemolysis assay and Etest glycopeptide resistance
      detection (GRD) method. The delta-hemolysis assay could be read at 24h and was
      more sensitive and specific than the Etest GRD at 24h and 48 h for detection of
      hVISA. Because most hVISA isolates have a vancomycin MIC of 2 MUg/mL, we
      recommend screening MRSA isolates first using Etest for those with an MIC of 2
      MUg/mL and then performing the delta-hemolysis assay on these isolates for hVISA.

PMID- 25600844
TI  - Influence of spinal cord lesion level and severity on H-reflex excitability and
      recovery curve.
AB  - INTRODUCTION: Changes in spinal reflexes can result from alterations in the
      spinal cord and descending pathways. We studied whether H-reflex excitability and
      its recovery depend on the level and/or severity of spinal cord injury (SCI).
      METHODS: The soleus Hmax and Mmax responses and the H-reflex recovery curve (HRC)
      at interstimulus intervals (ISIs) ranging from 50 to 1,000 ms were recorded in 38
      SCI individuals and 18 healthy subjects. RESULTS: Amplitude of Mmax correlated
      with level and severity of lesion (smaller amplitude correlated with more severe
      SCI or with more caudal lesion). Hmax/Mmax correlated only with age in the SCI
      group. HRC was increased significantly in complete SCI at ISIs < 500 ms and in
      incomplete SCI at ISIs > 200 ms with respect to healthy subjects. CONCLUSIONS:
      The changes in spinal reflexes as measured by the H-reflex and its recovery curve
      after SCI depend on the severity, but not on the level of the lesion.

PMID- 25600845
TI  - Perceptions and experiences of community members serving on institutional review
      boards: a questionnaire based study.
AB  - The community representative plays a very important role in an institutional
      review board (IRB) but there is sparse data about their understanding of their
      role in an IRB. This study was conducted to assess perceptions of community
      members serving on IRBs of one region in India. A validated questionnaire
      (Cohen's kappa coefficient of 0.84) was administered to community members of IRBs
      in a prospective cross-sectional study. The questions related to demography,
      perceptions of their role in the IRB, experiences while serving on the IRBs,
      difficulties faced by them, and suggestions to improve their contributions. Of
      the 56 IRBs contacted, all 15 of the public institutions shared details of their
      community members, while only 26 of the 41 IRBs of private institutions
      responded. When questioned about why they joined the IRB, one third of the
      respondents said either that there was "no specific reason" for joining or that
      they accepted the invitation to serve on the insistence of other members of the
      IRBs or the head of their institution. All except one felt that community members
      were needed for optimal functioning. Six participants said that they did not
      review informed consent documents (ICD), and 10 were unaware that their presence
      was vital for quorum to be met. Twenty-eight said they participated actively in
      meetings and did not feel intimidated by the presence of clinicians. Twelve
      reported difficulties in understanding medical terminologies in ICDs. Although
      the majority of participants were aware about their role in an IRB, some did not
      review important documents such as ICDs. Restricted participation by private
      hospital IRBs was a striking observation in our study. There is a need to define
      eligibility criteria and develop targeted training modules for community members
      to ensure their effective contribution to effective oversight of clinical
      research. 

PMID- 25600847
TI  - Successful lung retransplantation in a patient with acute fibrinous and
      organizing pneumonia: a case report.
AB  - Acute fibrinous and organizing pneumonia (AFOP) is an unusual histopathologic
      pattern characterized by the formation of intra-alveolar plugs of fibrin
      deposition and associated organizing pneumonia. AFOP is considered to be a form
      of rejection and portends a dismal prognosis. Here, we present the case of a
      young male patient who initially underwent a double lung transplantation for
      cystic fibrosis. After 42 months of regular follow-up, he experienced rapidly
      progressive respiratory failure. Acute rejection and opportunistic lung
      infections were suspected. The clinical conditions rapidly deteriorated despite
      treatment with broad-spectrum antibiotics and high-dose steroids. Therefore, AFOP
      was suspected owing to: 1) acute clinical presentation; 2) pulmonary computerized
      tomographic data; 3) typical histopathologic findings on transbronchial
      biopsieseconds, and 4) lack of response to different treatments. The patient
      required an emergency bilateral lung retransplantation 44 months after the
      initial transplantation. The histopathologic analysis of the explanted lungs
      confirmed the diagnosis of AFOP. Two years after the 2nd transplant, the patient
      is alive and well. To the best of our knowledge, this is the 1st case of a
      patient experiencing AFOP following lung transplantation who was successfully
      rescued by a 2nd bilateral lung retransplantation. 

PMID- 25600848
TI  - Can dietary intake influence perception of and measured appearance? A systematic
      review.
AB  - Appearance-based interventions have had some success in reducing smoking and sun
      exposure. Appearance may also motivate dietary behavior change if it was
      established that dietary improvement had a positive impact on appearance. The
      aims of this review are to evaluate the current evidence examining the
      relationship between dietary intake and appearance and to determine the
      effectiveness of dietary interventions on perceived or actual appearance. An
      electronic search of English-language studies up to August 2012 was conducted
      using Cochrane, MEDLINE, Embase, CINAHL, Web of Science, SCOPUS, and PsycINFO
      databases. Studies that included participants aged at least 18 years, that
      observed or altered dietary intake from actual food or dietary supplement use,
      and assessed appearance-related outcomes were considered eligible. Data from 27
      studies were extracted and assessed for quality using standardized tools.
      Nineteen studies were assessed as being of "positive" and 4 of "neutral" quality.
      All observational studies (n = 4741 participants) indicated that there was a
      significant association between various aspects of dietary intake and skin
      coloration and skin aging. The majority (16 studies, 769 participants) evaluated
      the effect of dietary supplements on skin appearance among women. Only 1 study
      examined the effect of actual food intake on appearance. Significant improvements
      in at least 1 actual or perceived appearance-related outcome (facial wrinkling,
      skin elasticity, roughness, and skin color) following dietary intervention were
      shown as a result of supplementation. Further studies are needed in
      representative populations that examine actual food intake on appearance, using
      validated tools in well-designed high-quality randomized control trials. 

PMID- 25600849
TI  - Electron transfer rate modulation in a compact Re(I) donor-acceptor complex.
AB  - Formation of the charge transfer state with the rate constant of (10 ps)(-1) has
      recently been reported for the complex fac-[Re(I)(CO)3(DCEB)(3DMABN)] (ReEBA);
      where 3DMABN is 3-dimethylaminobenzonitrile, serving as an electron donor, and
      DCEB is 4,4'-(dicarboxyethyl)-2,2-bipyridine, serving as an electron acceptor (Y.
      Yue et al., J. Phys. Chem. A, 118, 10407). 3-Pulse UV-pump - IR-pump - IR-probe
      spectroscopy is used in this work to study how the charge separation reaction in
      ReEBA to form a ligand to ligand charge transfer state (LLCT) can be modulated by
      vibrational excitation of various modes of the complex. While no significant rate
      modulation was found when the cyano group stretching mode of the 3DMABN donor was
      excited, a sizable effect was found when the ring stretching mode of the DCEB
      acceptor was excited. The accumulation of the charge separated state (LLCT state)
      in the 3-pulse experiment was observed as a sharp excited-state vibrational peak
      of the symmetric stretch of the three facial carbonyl groups, nuSS(CO). Modeling
      indicates that the rate of charge separation is increased by ca. 28% when
      vibrational excitation is present. The vibronic coupling signal of the bpy ring
      mode and nuSS(CO) as well as the energy transport dynamics from bpy to carbonyl
      contributed to the 3-pulse signal and was studied as well using the 3-pulse
      method. Energy transport between the same modes in the ground electronic state
      was measured by relaxation-assisted two-dimensional infrared (RA 2DIR)
      spectroscopy. The energy transport times of 4 +/- 0.7 and 5 +/- 1.5 ps were found
      for the ground and excited electronic states. 

PMID- 25600851
TI  - Thumb carpometacarpal joint total arthroplasty: a systematic review.
AB  - Thumb carpometacarpal joint total arthroplasty has been undertaken for many
      years. The proponents believe the short-term outcomes are better than
      trapeziectomy and its variants, but the longer term complications are often
      higher. This systematic review of all peer reviewed articles on thumb
      carpometacarpal joint total arthroplasty for osteoarthritis shows that there are
      reports of many implants. Some are no longer available. The reported outcomes are
      very variable: for some there are good long-term outcomes to beyond 10 years ;
      for others there are unacceptably high early rates of failure. Overall the
      published evidence does not show that total arthroplasty is better than
      trapeziectomy and its variants yet there is a higher complication rate and
      significant extra cost of using an implant. Future research needs to compare
      total arthroplasty with trapeziectomy to assess short term results where the
      arthroplasties may be better, long-term outcomes and the healthcare and personal
      costs so that surgeons and patients can make fully informed choices about the
      treatment of symptomatic thumb carpometacarpal joint osteoarthritis.

PMID- 25600850
TI  - A cross-sectional study of pain sensitivity, disease-activity assessment, mental
      health, and fibromyalgia status in rheumatoid arthritis.
AB  - INTRODUCTION: Pain remains the most important problem for people with rheumatoid
      arthritis (RA). Active inflammatory disease contributes to pain, but pain due to
      non-inflammatory mechanisms can confound the assessment of disease activity. We
      hypothesize that augmented pain processing, fibromyalgic features, poorer mental
      health, and patient-reported 28-joint disease activity score (DAS28) components
      are associated in RA. METHODS: In total, 50 people with stable, long-standing RA
      recruited from a rheumatology outpatient clinic were assessed for pain-pressure
      thresholds (PPTs) at three separate sites (knee, tibia, and sternum), DAS28,
      fibromyalgia, and mental health status. Multivariable analysis was performed to
      assess the association between PPT and DAS28 components, DAS28-P (the proportion
      of DAS28 derived from the patient-reported components of visual analogue score
      and tender joint count), or fibromyalgia status. RESULTS: More-sensitive PPTs at
      sites over or distant from joints were each associated with greater reported
      pain, higher patient-reported DAS28 components, and poorer mental health. A high
      proportion of participants (48%) satisfied classification criteria for
      fibromyalgia, and fibromyalgia classification or characteristics were each
      associated with more sensitive PPTs, higher patient-reported DAS28 components,
      and poorer mental health. CONCLUSIONS: Widespread sensitivity to pressure-induced
      pain, a high prevalence of fibromyalgic features, higher patient-reported DAS28
      components, and poorer mental health are all linked in established RA. The
      increased sensitivity at nonjoint sites (sternum and anterior tibia), as well as
      over joints, indicates that central mechanisms may contribute to pain sensitivity
      in RA. The contribution of patient-reported components to high DAS28 should
      inform decisions on disease-modifying or pain-management approaches in the
      treatment of RA when inflammation may be well controlled.

PMID- 25600852
TI  - Zone 2 rupture of finger flexor tendons due to sharp bone spikes at volarly
      dislocated metacarpophalangeal joints in patients with rheumatoid arthritis.

PMID- 25600853
TI  - Efficacy of platelet-rich plasma injections for chronic medial epicondylitis.

PMID- 25600854
TI  - The performance of magnetic resonance imaging in the detection of triangular
      fibrocartilage complex injury: a meta-analysis.
AB  - The aim of this study was to evaluate the accuracy of magnetic resonance imaging
      in the detection of triangular fibrocartilage complex injury through a meta
      analysis. A comprehensive literature search was conducted before 1 April 2014.
      All studies comparing magnetic resonance imaging results with arthroscopy or open
      surgery findings were reviewed, and 25 studies that satisfied the eligibility
      criteria were included. Data were pooled to yield pooled sensitivity and
      specificity, which were respectively 0.83 and 0.82. In detection of central and
      peripheral tears, magnetic resonance imaging had respectively a pooled
      sensitivity of 0.90 and 0.88 and a pooled specificity of 0.97 and 0.97. Six high
      quality studies using Ringler's recommended magnetic resonance imaging parameters
      were selected for analysis to determine whether optimal imaging protocols yielded
      better results. The pooled sensitivity and specificity of these six studies were
      0.92 and 0.82, respectively. The overall accuracy of magnetic resonance imaging
      was acceptable. For peripheral tears, the pooled data showed a relatively high
      accuracy. Magnetic resonance imaging with appropriate parameters are an ideal
      method for diagnosing different types of triangular fibrocartilage complex tears.

PMID- 25600855
TI  - Post-activation depression in the human soleus muscle using peripheral nerve and
      transcutaneous spinal stimulation.
AB  - Transcutaneous stimulation of the human lumbar spine can be used to elicit root
      evoked potentials (REPs). These sensory-motor responses display notable
      similarities to the monosynaptic H-reflex. The purpose of this study was to
      compare post-activation depression of the soleus REP to that of the H-reflex,
      when conditioned by either an H-reflex or an REP. Paired pulses were delivered 25
      200ms apart and the recovery was characterized using three levels of stimulation.
      In all conditions, post-activation depression was reduced during contraction as
      compared to rest (P<0.001). REP doublets, delivered using an inter-pulse interval
      of 150ms, recovered to 68+/-8% of control during plantarflexion and 20+/-6% of
      control at rest. During contraction, recovery of a second REP was 65% of the
      corresponding recovery for a second H-reflex. The recovery of an H-reflex was
      equivalent, when conditioned by either an H-reflex or an REP, even though the
      spinal stimulus activated and/or engaged more afferent and efferent fibers. Our
      results suggest that the additional elements activated by the spinal stimulus did
      not affect the recovery of the H-reflex. However, the transcutaneous spinal
      stimulus produced more inhibition when it was assessed using two low-intensity
      REPs (P<0.05) suggesting that the pathway mediating the spinally-evoked response
      was more susceptible to being inhibited. 

PMID- 25600856
TI  - Self-perceived and actual ability in the functional reach test in patients with
      Parkinson's disease.
AB  - Falls frequently occur during daily activities such as reaching for an object in
      patients with Parkinson's disease (PD). Misjudgment is also reported to be one of
      the circumstances that lead to falls. The functional reach test is an indicator
      of dynamic balance. The primary objective was to establish whether there is a
      difference between self-perceived and actual ability to perform the functional
      reach test in patients with PD who have never fallen. Three groups of
      participants (all with no history of falls) were studied: young adults, elderly
      adults and PD patients. The participants first estimated their maximum reaching
      distance (but without performing the action, i.e. as a motor imagery task) and
      then actually performed the functional reach test (i.e. as a motor task). No
      significant overestimation or underestimation was observed. The reaching distance
      was lower in PD than in the two other groups. There were no differences between
      PD patients and elderly adults in terms of the forward centre of pressure
      displacement. Seven PD patients reported a fall in the year following the
      experiment. The fallers had a longer history of disease. Finally, PD patients
      adequately estimated their ability in the functional reach test and did not adopt
      an "at risk" strategy and appeared to be quite conservative (as were healthy
      elderly adults) in their postural control behavior. Ability to estimate self
      performance is preserved in PD patients with no clinical impairments of postural
      control although they are at risk of future falls. 

PMID- 25600857
TI  - Elevated serum leptin levels are associated with good nutritional status in non
      obese chronic hemodialysis patients.
AB  - OBJECTIVE: Leptin is a hormone and a proinflammatory cytokine secreted from
      adipocytes, which functions to suppress appetite in healthy persons. Serum leptin
      levels are significantly elevated in patients with end-stage renal disease (ESRD)
      primarily due to decreased clearance by the kidneys The consequence of
      hyperleptinemia in ESRD is not fully understood. We aimed to investigate the
      association between serum leptin levels and nutrition/inflammation status in non
      obese chronic hemodialysis (HD) patients. METHODS: 65 chronic, anuric, nonobese
      (body mass index (BMI) < 25 kg/m2) HD patients were included in this cross
      sectional study. Demographic, anthropometric, and biochemical data were obtained
      from all patients to determine nutrition and inflammation status. Patients were
      classified into the 3 groups according to serum leptin levels; group 1 (low
      leptin, n = 9), group 2 (normal leptin, n = 31), and group 3 (high leptin, n =
      25). RESULTS: Mean age and duration on dialysis of 65 patients (male/female:
      34/31) were 51.6 +/- 17.8 years and 78.0 +/- 67.9 months, respectively. Serum
      leptin levels increased with older age, female gender, higher BMI and triceps
      skinfold thickness. Elevated serum leptin levels were significantly associated
      with good nutritional status parameters, such as higher albumin (p = 0.001),
      prealbumin (p = 0.033), total iron binding capacity (p = 0.045), total
      cholesterol (p = 0.041), and lower malnutrition inflammation score (MIS) (p =
      0.002). Serum leptin levels remained a negative correlation with MIS after
      adjustments made for BMI. No correlation was established between leptin and
      inflammation parameters including ferritin, highly sensitive C-reactive protein
      (hs-CRP), and tumor necorsis factor alpha (TNF-alpha). CONCLUSION: Elevated serum
      leptin levels seem to be associated with good nutritional status. However, there
      was no correlation between leptin and inflammatory status.

PMID- 25600858
TI  - Saving two lives with one dialysis treatment.
AB  - Hemodialysis is the extracorporeal treatment of choice for various life
      threatening intoxications, with the exception of highly protein-bound substances,
      which are preferably removed by charcoal hemoperfusion. This technique, however,
      is limited by its availability and its significant side effects. We present a
      potentially lifethreatening diphenhydramine (DPH) overdose in a stuporous female
      patient in which high cut-off hemodialysis was used. Timely detoxification
      resulted in rapid gain of consciousness, allowing the patient to state the
      existence and location of another poison victim. 

PMID- 25600859
TI  - Glomerulonephritis and cryoglobulinemia: first manifestation of visceral
      leishmaniasis.
AB  - Visceral leishmaniasis due to Leishmania Infantum is an endemic parasitic
      infection in the Mediterranean area. Since 2009, Europe's largest outbreak of
      Leishmaniasis has been reported in the region of Madrid (Spain). Renal
      involvement is an unusual complication. Different forms of renal disease have
      been described: interstitial, glomerular, and vascular damage. Direct invasion of
      renal parenchyma by the parasite has been described as a mechanism of kidney
      damage, especially in the immunocompromised. Immune complex deposition and T
      cells adhesion molecules activation have demonstrated that a pathogenic role in
      glomerulonephritis related to visceral leishmaniasis. The association between
      mixed cryoglobulinemia and visceral leishmaniasis has been previously reported in
      six patients. Renal involvement is only described in one of them. From July 2009
      to October 2012, 4 patients with membranoproliferative glomerulonephritis and
      mixed cryoglobulinemia with negative serology for hepatitis B and C were
      diagnosed in our hospital. Serology of Leishmania in serum bank samples was
      performed; it was positive in 3 patients. Leishmania parasite was confirmed by
      other tests. We present 3 patients with mixed cryoglobulinemia and
      membranoproliferative glomerulonephritis as first clinical manifestation of
      visceral leishmaniasis. 

PMID- 25600860
TI  - Postoperative radiation therapy for patients at high-risk of recurrence after
      radical prostatectomy: does timing matter?
AB  - OBJECTIVE: To evaluate among radical prostatectomy (RP) patients at high-risk of
      recurrence whether the timing of postoperative radiation therapy (RT) (adjuvant,
      early salvage with detectable post-RP prostate-specific antigen [PSA], or 'late'
      salvage with a PSA level of >1.0 ng/mL) is significantly associated with overall
      survival (OS), prostate-cancer specific survival or metastasis-free survival, in
      a longitudinal cohort. PATIENTS AND METHODS: Of 6 176 RP patients in the Cancer
      of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 305 patients with
      high-risk pathological features (margin positivity, Gleason score 8-10, or pT3-4)
      who underwent postoperative RT were examined, either in the adjuvant (<=6 months
      after RP with undetectable PSA levels, 76 patients) or salvage setting (>6 months
      after RP or pre-RT PSA level of >0.1 ng/mL, 229 patients). Early (PSA level of
      <=1.0 ng/mL, 180 patients) or late salvage RT (PSA level >1.0 ng/mL, 49 patients)
      was based on post-RP, pre-RT PSA level. Multivariable Cox regression examined
      associations with all-cause mortality and prostate cancer-specific mortality
      and/or metastases (PCSMM). RESULTS: After a median of 74 months after RP, 65 men
      had died (with 37 events of PCSMM). Adjuvant and salvage RT patients had
      comparable high-risk features. Compared with adjuvant, salvage RT (early or late)
      had an increased association with all-cause mortality (hazard ratio [HR] 2.7, P =
      0.018) and with PCSMM (HR 4.0, P = 0.015). PCSMM-free survival differed by
      further stratification of timing, with 10-year estimates of 88%, 84%, and 71% for
      adjuvant, early salvage, and late salvage RT, respectively (P = 0.026). For PCSMM
      free survival and OS, compared with adjuvant RT, late salvage RT had
      statistically significantly increased risk; however, early salvage RT did not.
      CONCLUSION: This analysis suggests that patients who underwent early salvage RT
      with PSA levels of <1.0 ng/mL may have comparable metastasis-free survival and OS
      compared with adjuvant RT; however, late salvage RT with a PSA level of >1.0
      ng/mL is associated with worse clinical outcomes.

PMID- 25600861
TI  - The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive
      Medication Use.
AB  - OBJECTIVE: The objective of this study is to examine how nursing homes changed
      their use of antipsychotic and other psychoactive medications in response to
      Nursing Home Compare's initiation of publicly reporting antipsychotic use in July
      2012. RESEARCH DESIGN AND SUBJECTS: The study includes all state recertification
      surveys (n = 40,415) for facilities six quarters prior and post the initiation of
      public reporting. Using a difference-in-difference framework, the change in use
      of antipsychotics and other psychoactive medications is compared for facilities
      subject to public reporting and facilities not subject to reporting. PRINCIPAL
      FINDINGS: The percentage of residents using antipsychotics, hypnotics, or any
      psychoactive medication is found to decline after public reporting. Facilities
      subject to reporting experienced an additional decline in antipsychotic use (
      1.94 vs. -1.40 percentage points) but did not decline as much for hypnotics (
      0.60 vs. -1.21 percentage points). Any psychoactive use did not vary with
      reporting status, and the use of antidepressants and anxiolytics did not change.
      CONCLUSION: Public reporting of an antipsychotic quality measure can be an
      effective policy tool for reducing the use of antipsychotic medications--though
      the effect many only exist in the short run.

PMID- 25600863
TI  - Clinical data miner: an electronic case report form system with integrated data
      preprocessing and machine-learning libraries supporting clinical diagnostic model
      research.
AB  - BACKGROUND: Using machine-learning techniques, clinical diagnostic model research
      extracts diagnostic models from patient data. Traditionally, patient data are
      often collected using electronic Case Report Form (eCRF) systems, while
      mathematical software is used for analyzing these data using machine-learning
      techniques. Due to the lack of integration between eCRF systems and mathematical
      software, extracting diagnostic models is a complex, error-prone process.
      Moreover, due to the complexity of this process, it is usually only performed
      once, after a predetermined number of data points have been collected, without
      insight into the predictive performance of the resulting models. OBJECTIVE: The
      objective of the study of Clinical Data Miner (CDM) software framework is to
      offer an eCRF system with integrated data preprocessing and machine-learning
      libraries, improving efficiency of the clinical diagnostic model research
      workflow, and to enable optimization of patient inclusion numbers through study
      performance monitoring. METHODS: The CDM software framework was developed using a
      test-driven development (TDD) approach, to ensure high software quality.
      Architecturally, CDM's design is split over a number of modules, to ensure future
      extendability. RESULTS: The TDD approach has enabled us to deliver high software
      quality. CDM's eCRF Web interface is in active use by the studies of the
      International Endometrial Tumor Analysis consortium, with over 4000 enrolled
      patients, and more studies planned. Additionally, a derived user interface has
      been used in six separate interrater agreement studies. CDM's integrated data
      preprocessing and machine-learning libraries simplify some otherwise manual and
      error-prone steps in the clinical diagnostic model research workflow.
      Furthermore, CDM's libraries provide study coordinators with a method to monitor
      a study's predictive performance as patient inclusions increase. CONCLUSIONS: To
      our knowledge, CDM is the only eCRF system integrating data preprocessing and
      machine-learning libraries. This integration improves the efficiency of the
      clinical diagnostic model research workflow. Moreover, by simplifying the
      generation of learning curves, CDM enables study coordinators to assess more
      accurately when data collection can be terminated, resulting in better models or
      lower patient recruitment costs.

PMID- 25600864
TI  - Quantitative pediatric surgical skill assessment using a rapid-prototyped chest
      model.
AB  - INTRODUCTION: Though minimally invasive pediatric surgery has become more
      widespread, pediatric-specific surgical skills have not been quantitatively
      assessed. MATERIAL AND METHODS: As a first step toward the quantification of
      pediatric-specific surgical skills, a pediatric chest model comprising a three
      dimensional rapid-prototyped pediatric ribcage with accurate anatomical
      dimensions, a suturing skin model with force-sensing capability, and forceps with
      motion-tracking sensors were developed. A skill assessment experiment was
      conducted by recruiting 16 inexperienced pediatric surgeons and 14 experienced
      pediatric surgeons to perform an endoscopic intracorporeal suturing and knot
      tying task in both the pediatric chest model setup and the conventional box
      trainer setup. RESULTS: The instrument motion measurement was successful in only
      20 surgeons due to sensor failure. The task completion time, total path length of
      instruments, and applied force were compared between the inexperienced and
      experienced surgeons as well as between the box trainer and chest model setups.
      The experienced surgeons demonstrated better performance in all parameters for
      both setups, and the pediatric chest model was more challenging due to the
      pediatric features replicated by the model. CONCLUSION: The pediatric chest model
      was valid for pediatric skill assessment, and further analysis of the collected
      data will be conducted to further investigate pediatric-specific skills.

PMID- 25600862
TI  - Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the
      prediction of the skin sensitizing potential of chemicals.
AB  - INTRODUCTION: Allergic contact dermatitis (ACD) is a skin disease characterized
      by eczema and itching. A considerable proportion of chemicals induce ACD in
      humans. More than 10,000 substances should be tested for skin sensitization
      potential under the Registration, Evaluation, Authorization and Restriction of
      Chemical substances (REACH) regulation. The Local Lymph Node Assay (LLNA) has
      been designated as the first-choice in vivo assay for sensitization testing by
      REACH. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the
      LLNA. For both the LLNA and the LLNA:BrdU-ELISA, CBA/JN mouse is the preferred
      mouse strain recommended in the regulatory guidelines. However, the availability
      of CBA/JN mouse in China is only limited to a few animal suppliers, which makes
      the mouse difficult to obtain. BALB/c mouse, which is widely commercially
      available, is considered for alternative use but it can only be used in the assay
      after it has been evaluated by formal validation study. Thus, a validation study
      was conducted in our laboratory to determine if BALB/c mouse could also be used
      in the LLNA:BrdU-ELISA. METHODS: Forty-three test substances including 32 LLNA
      sensitizers and 11 LLNA non-sensitizers, their vehicles and each concentration
      used were the same as that used in the formal validation study for the LLNA:BrdU
      ELISA using CBA/JN mouse. Female BALB/c mice of 8-10 weeks old were randomly
      allocated to groups (four mice per group). The test substance (25 MUl) or the
      vehicle alone was applied to the dorsum of both ears daily for 3 consecutive
      days. A single intraperitoneal injection of 0.5 ml of BrdU (10mg/ml) solution was
      given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was
      excised, weighed and stored at -20 degrees C until BrdU-ELISA was conducted.
      RESULTS: This validation study for the LLNA:BrdU-ELISA using BALB/c mouse
      correctly identified 30 of 31 sensitizers and 8 of 11 non-sensitizers. The
      accuracy, sensitivity, specificity, false positive rate, false negative rate,
      positive predictivity values and negative predictivity values in this study,
      which could indicate the performance of the LLNA:BrdU-ELISA using BALB/c mouse,
      were not different statistically from that of the validation study for the
      LLNA:BrdU-ELISA using CBA/JN mouse. DISCUSSION: This validation study indicates
      that BALB/c mouse could be used alternatively in the LLNA:BrdU-ELISA for the
      prediction of the skin sensitizing potential of chemicals.

PMID- 25600865
TI  - Single-incision versus conventional three-port laparoscopic appendectomy: A meta
      analysis of randomized controlled trials.
AB  - PURPOSE: The aim of this article was to compare the advantages and disadvantages
      of single-incision laparoscopic appendectomy (SILA) and conventional three-port
      laparoscopic appendectomy (CTLA). MATERIAL AND METHODS: A meta-analysis was
      performed by analyzing all randomized controlled trials (RCTs) published in
      English that compared SILA and CTLA for appendicitis in adults and children.
      These studies compared these two methods from different angles including outcomes
      of interest, patient characteristics, operative time, pain visual analogue scales
      scores (VAS scores), length of hospital stay, time to return to full activity,
      resumption of diet, postoperative complications and cosmetic results The risk
      ratios (RR) and mean difference (MD) with 95% confidence intervals (CIs) were
      employed to assess the outcome. RESULTS: Seven recent RCTs encompassing 1170
      patients (586 SILA and 584 CTLA cases) were included in this meta-analysis. The
      pooled results demonstrated that conversion rate, drain inserted, reoperation,
      length of hospital stay, resumption of normal diet and postoperative
      complications were statistically comparable between the two groups. The
      postoperative abdominal pain within 24 h was -0.57 in favor of the SILA technique
      (p = 0.05). Compared with CTLA, SILA showed a better cosmetic satisfaction score
      (SMD, 0.58; 95% CI, 0.32-0.83; p < 0.0001) and shorter time to recover normal
      activity (WMD, -0.69; 95% CI, -1.11-0.26; p = 0.001). However, SILA has a longer
      operative time (WMD, 5.38; 95% CI, 2.94-7.83; p < 0.0001). CONCLUSIONS: In
      selected patients, SILA was confirmed to be as safe and effective as CTLA.
      Despite the longer operative time, SILA has higher cosmetic satisfaction and
      shorter recovery time to normal activity. Due to the limitations of the available
      data, further research is needed.

PMID- 25600866
TI  - Cooperation between Noncanonical Ras Network Mutations.
AB  - Cancer develops after the acquisition of a collection of mutations that together
      create the cancer phenotype. How collections of mutations work together within a
      cell and whether there is selection for certain combinations of mutations are not
      well understood. We investigated this problem with a mathematical model of the
      Ras signaling network, including a computational random mutagenesis. Modeling and
      subsequent experiments revealed that mutations of the tumor suppressor gene NF1
      can amplify the effects of other Ras pathway mutations, including weakly
      activating, noncanonical Ras mutants. Furthermore, analyzing recently available,
      large, cancer genomic data sets uncovered increased co-occurrence of NF1
      mutations with mutations in other Ras network genes. Overall, these data suggest
      that combinations of Ras pathway mutations could serve the role of cancer
      "driver." More generally, this work suggests that mutations that result in
      network instability may promote cancer in a manner analogous to genomic
      instability.

PMID- 25600867
TI  - The Edges of Pancreatic Islet beta Cells Constitute Adhesive and Signaling
      Microdomains.
AB  - Pancreatic islet beta cells are organized in rosette-like structures around blood
      vessels and exhibit an artery-to-vein orientation, but they do not display the
      typical epithelial polarity. It is unclear whether these cells present a
      functional asymmetry related to their spatial organization. Here, we identify
      murine beta cell edges, the sites at which adjacent cell faces meet at a sharp
      angle, as surface microdomains of cell-cell adhesion and signaling. The edges are
      marked by enrichment of F-actin and E-cadherin and are aligned between
      neighboring cells. The edge organization is E-cadherin contact dependent and
      correlates with insulin secretion capacity. Edges display elevated levels of
      glucose transporters and SNAP25 and extend numerous F-actin-rich filopodia. A
      similar beta cell edge organization was observed in human islets. When
      stimulated, beta cell edges exhibit high calcium levels. In view of the
      functional importance of intra-islet communication, the spatial architecture of
      their edges may prove fundamental for coordinating physiological insulin
      secretion.

PMID- 25600869
TI  - A Long Noncoding RNA on the Ribosome Is Required for Lifespan Extension.
AB  - The biogenesis of ribosomes and their coordination of protein translation consume
      an enormous amount of cellular energy. As such, it has been established that the
      inhibition of either process can extend eukaryotic lifespan. Here, we used next
      generation sequencing to compare ribosome-associated RNAs from normal strains of
      Caenorhabditis elegans to those carrying the life-extending daf-2 mutation. We
      found a long noncoding RNA (lncRNA), transcribed telomeric sequence 1 (tts-1), on
      ribosomes of the daf-2 mutant. Depleting tts-1 in daf-2 mutants increases
      ribosome levels and significantly shortens their extended lifespan. We find tts-1
      is also required for the longer lifespan of the mitochondrial clk-1 mutants but
      not the feeding-defective eat-2 mutants. In line with this, the clk-1 mutants
      express more tts-1 and fewer ribosomes than the eat-2 mutants. Our results
      suggest that the expression of tts-1 functions in different longevity pathways to
      reduce ribosome levels in a way that promotes life extension.

PMID- 25600868
TI  - The TMAO-Generating Enzyme Flavin Monooxygenase 3 Is a Central Regulator of
      Cholesterol Balance.
AB  - Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide
      (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we
      performed transcriptional profiling in mouse models of altered reverse
      cholesterol transport (RCT) and serendipitously identified the TMAO-generating
      enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol
      metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary
      lipid secretion, blunts intestinal cholesterol absorption, and limits the
      production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3
      knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT,
      thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates
      hepatic endoplasmic reticulum (ER) stress and inflammation in part by decreasing
      hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified
      as a central integrator of hepatic cholesterol and triacylglycerol metabolism,
      inflammation, and ER stress. These studies suggest that the gut microbiota-driven
      TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.

PMID- 25600870
TI  - Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons
      Impairs Cortical Map Development.
AB  - Polymorphisms that alter serotonin transporter SERT expression and functionality
      increase the risks for autism and psychiatric traits. Here, we investigate how
      SERT controls serotonin signaling in developing CNS in mice. SERT is transiently
      expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic
      serotonin during perinatal CNS development. We show that SERT expression in
      glutamatergic thalamocortical axons (TCAs) dictates sensory map architecture.
      Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial
      organizations of cortical neurons, and dendritic arborization in sensory cortex.
      Pharmacological reduction of serotonin synthesis during the first postnatal week
      rescues sensory maps in SERTGluDelta mice. Furthermore, knockdown of SERT
      expression in serotonin-producing neurons does not impair barrel maps. We propose
      that spatiotemporal SERT expression in non-serotonin-producing neurons represents
      a determinant in early life genetic programming of cortical circuits. Perturbing
      this SERT function could be involved in the origin of sensory and cognitive
      deficits associated with neurodevelopmental disorders.

PMID- 25600871
TI  - Network Diffusion Model of Progression Predicts Longitudinal Patterns of Atrophy
      and Metabolism in Alzheimer's Disease.
AB  - Alzheimer's disease pathology (AD) originates in the hippocampus and subsequently
      spreads to temporal, parietal, and prefrontal association cortices in a
      relatively stereotyped progression. Current evidence attributes this orderly
      progression to transneuronal transmission of misfolded proteins along the
      projection pathways of affected neurons. A network diffusion model was recently
      proposed to mathematically predict disease topography resulting from
      transneuronal transmission on the brain's connectivity network. Here, we use this
      model to predict future patterns of regional atrophy and metabolism from baseline
      regional patterns of 418 subjects. The model accurately predicts end-of-study
      regional atrophy and metabolism starting from baseline data, with significantly
      higher correlation strength than given by the baseline statistics directly. The
      model's rate parameter encapsulates overall atrophy progression rate; group
      analysis revealed this rate to depend on diagnosis as well as baseline
      cerebrospinal fluid (CSF) biomarker levels. This work helps validate the model as
      a prognostic tool for Alzheimer's disease assessment.

PMID- 25600873
TI  - Prolonged Ezh2 Depletion in Glioblastoma Causes a Robust Switch in Cell Fate
      Resulting in Tumor Progression.
AB  - EZH2 is frequently overexpressed in glioblastoma (GBM), suggesting an oncogenic
      function that could be a target for therapeutic intervention. However, reduced
      EZH2 activity can also promote tumorigenesis, leading to concerns about the use
      of EZH2 inhibitors. Here, we provide further insight about the effects of
      prolonged Ezh2 inhibition in glioblastoma using preclinical mouse models and
      primary tumor-derived human GBM cell lines. Using doxycycline-inducible shRNAs
      that mimic the effects of a selective EZH2 inhibitor, we demonstrate that
      prolonged Ezh2 depletion causes a robust switch in cell fate, including
      significantly enhanced proliferation, DNA damage repair, and activation of part
      of the pluripotency network, resulting in altered tumor cell identity and tumor
      progression. Short-term Ezh2 depletion significantly improved survival without
      the tumor progression observed upon prolonged Ezh2 depletion, suggesting that
      precise dosing regiments are very important. These results could be of high
      clinical relevance with regard to how glioblastomas should be treated with
      epigenetic therapies.

PMID- 25600872
TI  - The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor
      Function.
AB  - The T-type calcium channel Cav3.2 emerges as a key regulator of sensory
      functions, but its expression pattern within primary afferent neurons and its
      contribution to modality-specific signaling remain obscure. Here, we elucidate
      this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by
      a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a
      selective marker of two major low-threshold mechanoreceptors (LTMRs), Adelta- and
      C-LTMRs, innervating the most abundant skin hair follicles. The presence of
      Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at
      multiple sites, setting their strong excitability. Strikingly, the C-LTMR
      specific knockout uncovers that Cav3.2 regulates light-touch perception and
      noxious mechanical cold and chemical sensations and is essential to build up that
      debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be
      entirely A-LTMR specific. Collectively, our findings support a fundamental role
      for Cav3.2 in touch/pain pathophysiology, validating their critic pharmacological
      relevance to relieve mechanical and cold allodynia.

PMID- 25600874
TI  - Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive
      Migration.
AB  - Integrin trafficking is key to cell migration, but little is known about the
      spatiotemporal organization of integrin endocytosis. Here, we show that
      alpha5beta1 integrin undergoes tensin-dependent centripetal movement from the
      cell periphery to populate adhesions located under the nucleus. From here, ligand
      engaged alpha5beta1 integrins are internalized under control of the Arf subfamily
      GTPase, Arf4, and are trafficked to nearby late endosomes/lysosomes. Suppression
      of centripetal movement or Arf4-dependent endocytosis disrupts flow of ligand
      bound integrins to late endosomes/lysosomes and their degradation within this
      compartment. Arf4-dependent integrin internalization is required for proper
      lysosome positioning and for recruitment and activation of mTOR at this cellular
      subcompartment. Furthermore, nutrient depletion promotes subnuclear accumulation
      and endocytosis of ligand-engaged alpha5beta1 integrins via inhibition of mTORC1.
      This two-way regulatory interaction between mTORC1 and integrin trafficking in
      combination with data describing a role for tensin in invasive cell migration
      indicate interesting links between nutrient signaling and metastasis.

PMID- 25600876
TI  - SART3-Dependent Accumulation of Incomplete Spliceosomal snRNPs in Cajal Bodies.
AB  - Cajal bodies (CBs) are evolutionarily conserved nuclear structures involved in
      the metabolism of spliceosomal small nuclear ribonucleoprotein particles
      (snRNPs). CBs are not present in all cell types, and the trigger for their
      formation is not yet known. Here, we depleted cells of factors required for the
      final steps of snRNP assembly and assayed for the presence of stalled
      intermediates in CBs. We show that depletion induces formation of CBs in cells
      that normally lack these nuclear compartments, suggesting that CB nucleation is
      triggered by an imbalance in snRNP assembly. Accumulation of stalled
      intermediates in CBs depends on the di-snRNP assembly factor SART3. SART3 is
      required for both the induction of CB formation as well as the tethering of
      incomplete snRNPs to coilin, the CB scaffolding protein. We propose a model
      wherein SART3 monitors tri-snRNP assembly and sequesters incomplete particles in
      CBs, thereby allowing cells to maintain a homeostatic balance of mature snRNPs in
      the nucleoplasm.

PMID- 25600875
TI  - Heparan Sulfate Proteoglycans Regulate Fgf Signaling and Cell Polarity during
      Collective Cell Migration.
AB  - Collective cell migration is a highly regulated morphogenetic movement during
      embryonic development and cancer invasion that involves the precise orchestration
      and integration of cell-autonomous mechanisms and environmental signals.
      Coordinated lateral line primordium migration is controlled by the regulation of
      chemokine receptors via compartmentalized Wnt/beta-catenin and fibroblast growth
      factor (Fgf) signaling. Analysis of mutations in two exostosin
      glycosyltransferase genes (extl3 and ext2) revealed that loss of heparan sulfate
      (HS) chains results in a failure of collective cell migration due to enhanced Fgf
      ligand diffusion and loss of Fgf signal transduction. Consequently, Wnt/beta
      catenin signaling is activated ectopically, resulting in the subsequent loss of
      the chemokine receptor cxcr7b. Disruption of HS proteoglycan (HSPG) function
      induces extensive, random filopodia formation, demonstrating that HSPGs are
      involved in maintaining cell polarity in collectively migrating cells. The HSPGs
      themselves are regulated by the Wnt/beta-catenin and Fgf pathways and thus are
      integral components of the regulatory network that coordinates collective cell
      migration with organ specification and morphogenesis.

PMID- 25600877
TI  - Rapid and Efficient Direct Conversion of Human Adult Somatic Cells into Neural
      Stem Cells by HMGA2/let-7b.
AB  - A recent study has suggested that fibroblasts can be converted into mouse-induced
      neural stem cells (miNSCs) through the expression of defined factors. However,
      successful generation of human iNSCs (hiNSCs) has proven challenging to achieve.
      Here, using microRNA (miRNA) expression profile analyses, we showed that let-7
      microRNA has critical roles for the formation of PAX6/NESTIN-positive colonies
      from human adult fibroblasts and the proliferation and self-renewal of hiNSCs.
      HMGA2, a let-7-targeting gene, enables induction of hiNSCs that displayed
      morphological/molecular features and in vitro/in vivo differentiation potential
      similar to H9-derived NSCs. Interestingly, HMGA2 facilitated the efficient
      conversion of senescent somatic cells or blood CD34+ cells into hiNSCs through an
      interaction with SOX2, whereas other combinations or SOX2 alone showed a limited
      conversion ability. Taken together, these findings suggest that HMGA2/let-7
      facilitates direct reprogramming toward hiNSCs in minimal conditions and
      maintains hiNSC self-renewal, providing a strategy for the clinical treatment of
      neurological diseases.

PMID- 25600878
TI  - Lipoprotein in the cell wall of Staphylococcus aureus is a major inducer of
      nitric oxide production in murine macrophages.
AB  - Staphylococcus aureus is a Gram-positive bacterium that causes inflammation at
      infection sites by inducing various inflammatory mediators such as nitric oxide
      (NO). To identify the staphylococcal virulence factors contributing to NO
      production, we compared the ability of ethanol-killed wild-type S. aureus and
      mutant strains lacking lipoteichoic acid (DeltaltaS), lipoproteins (Deltalgt), or
      d-alanine (DeltadltA) to stimulate NO production in a murine macrophage cell
      line, RAW 264.7, and the primary macrophages derived from C57BL/6 mice. Wild
      type, DeltaltaS, and DeltadltA strains induced NO production in a dose-dependent
      manner but this response was not observed when the cells were stimulated with the
      Deltalgt strain. Moreover, purified lipoproteins triggered NO production in
      macrophages. Coincident with NO induction, the wild-type, DeltaltaS, and
      DeltadltA strains induced expression of inducible NO synthase (iNOS) at both mRNA
      and protein levels whereas Deltalgt failed to induce iNOS protein or mRNA.
      Transient transfection followed by a reporter gene assay and Western blotting
      experiments demonstrated that wild-type, DeltaltaS, and DeltadltA strains, but
      not the Deltalgt strain, induced substantial activation of NF-kappaB and STAT1
      phosphorylation, both of which are known to be crucial for iNOS expression.
      Moreover, wild-type, DeltaltaS, and DeltadltA strains increased Toll-like
      receptor 2 (TLR2) activation, which is known to mediate S. aureus-induced innate
      immunity, whereas the Deltalgt strain did not. Collectively, these results
      suggest that lipoproteins in the cell wall of S. aureus play a major role in the
      induction of NO production in murine macrophages through activation of the TLR2
      receptor. 

PMID- 25600880
TI  - Contact allergy trends in Sweden - a retrospective comparison of patch test data
      from 1992, 2000, and 2009.
AB  - BACKGROUND: Contact allergy prevalence rates change over time as a result of
      variations in allergen exposure. Data from patch test clinics are often used as
      markers for allergy trends. OBJECTIVES: The aim of the present retrospective
      study was to describe trends in rates of sensitization to allergens in the
      Swedish baseline series. PATIENTS/MATERIALS/METHODS: Prevalence rates are
      described by comparing consecutive patch test data from 1992, 2000 and 2009 in
      Swedish patch test clinics. In total, 3680 patients were included in 1992, 3825
      in 2000, and 3112 in 2009. RESULTS: Among test substances with a sensitization
      rate above 2% in 2009, significant decreases were noted for nickel sulfate,
      cobalt chloride, colophonium, and methylchloroisothiazolinone
      (MCI)/methylisothiazolinone (MI), and a significant increase for p
      phenylenediamine, as compared with 1992. Potassium dichromate reactions had
      increased among younger women, whereas reactions to nickel and cobalt had
      decreased in this group. Sensitization to chromium, cobalt and fragrance mix I
      had decreased among older men, and sensitization to nickel had decreased among
      younger men. CONCLUSIONS: It is probable that these changes in 1992-2009 reflect
      both changes in regulations for nickel, lower levels of chromium in cement and of
      MCI/MI in cosmetics, and increasing use of hair dyes.

PMID- 25600879
TI  - Predicting inadequate bowel preparation for colonoscopy in participants receiving
      split-dose bowel preparation: development and validation of a prediction score.
AB  - BACKGROUND: Adequate bowel preparation is important for optimal colonoscopy. It
      is important to identify patients at risk for inadequate bowel preparation
      because this allows taking precautions in this specific group. OBJECTIVE: To
      develop a prediction score to identify patients at risk for inadequate bowel
      preparation who may benefit from an intensified bowel cleansing regimen. DESIGN:
      Patient and colonoscopy data were prospectively collected, whereas clinical data
      were retrospectively collected for a total of 1996 colonoscopies in participants
      who received split-dose bowel preparation. Multivariate logistic regression
      analyses were conducted in a random two-thirds of the cohort to develop a
      prediction model. Validation and evaluation of the discriminative power of the
      prediction model were performed within the remaining one-third of the cohort.
      SETTING: Four centers, including one academic and three medium-to-large size
      nonacademic centers. PATIENTS: Consecutive colonoscopies in November and December
      2012. Mean age was 57.3 +/- 15.9 years, 45.8% were male and indications for
      colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/or
      blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%).
      INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Inadequate bowel
      preparation defined as Boston Bowel Preparation Scale score <6. RESULTS: A total
      of 1331 colonoscopies were included in the development cohort, of which 172
      (12.9%) had an inadequate bowel preparation. Independent factors included in the
      prediction model were American Society of Anesthesiologists Physical Status
      Classification System score >=3, use of tricyclic antidepressants, use of
      opioids, diabetes, chronic constipation, history of abdominal and/or pelvic
      surgery, history of inadequate bowel preparation, and current hospitalization.
      The discriminative ability of the scale was good, with an area under the curve of
      0.77 in the validation cohort. LIMITATIONS: Study design partially retrospective,
      no data on patient compliance. CONCLUSION: We developed a validated, easy-to-use
      prediction scale that can be used to identify subjects with an increased risk of
      inadequate bowel preparation with good accuracy.

PMID- 25600881
TI  - Acceptability of financial incentives for encouraging uptake of healthy
      behaviours: A critical review using systematic methods.
AB  - OBJECTIVE: Financial incentives are effective in encouraging healthy behaviours,
      yet concerns about acceptability remain. We conducted a systematic review
      exploring acceptability of financial incentives for encouraging healthy
      behaviours. METHODS: Database, reference, and citation searches were conducted
      from the earliest available date to October 2014, to identify empirical studies
      and scholarly writing that: had an English language title, were published in a
      peer-reviewed journal, and explored acceptability of financial incentives for
      healthy behaviours in members of the public, potential recipients, potential
      practitioners or policy makers. Data was analysed using thematic analysis.
      RESULTS: Eighty one papers were included: 59 pieces of scholarly writing and 22
      empirical studies, primarily exploring acceptability to the public. Five themes
      were identified: fair exchange, design and delivery, effectiveness and cost
      effectiveness, recipients, and impact on individuals and wider society. Although
      there was consensus that if financial incentives are effective and cost effective
      they are likely to be considered acceptable, a number of other factors also
      influenced acceptability. CONCLUSIONS: Financial incentives tend to be acceptable
      to the public when they are effective and cost-effective. Programmes that benefit
      recipients and wider society; are considered fair; and are delivered to
      individuals deemed appropriate are likely to be considered more acceptable.

PMID- 25600882
TI  - The therapeutic impact of HNP-1 in condyloma acuminatum.
AB  - BACKGROUND: Condyloma acuminatum is one of the most commonly occurring sexually
      transmitted diseases. HNP1 is a small antimicrobial peptide that has been
      reported to have antiviral activities. AIM: Using the condyloma acuminatum tissue
      culture to resemble the situation more closely in vivo, we investigate the
      therapeutic effect of a recombinant plasmid encoding HNP1 gene in condyloma
      acuminatum tissue. METHODS: Recombinant plasmid DNA carrying HNP1 cDNA was
      constructed and identified. Then the recombinant plasmid was transfected into a
      condyloma acuminatum tissue fragment, and the HNP1 expression was determined on
      these tissue fragments by immunohistochemistry. TUNEL staining and flow cytometry
      techniques were used to examine cell apoptosis of condyloma acuminatum tissue.
      Relative real-time polymerase chain reaction was used to validate antihuman
      papillomavirus therapeutics of the treatment groups. RESULTS: Transfected HNP1
      gene was expressed mainly in the cytoplasmic granules of the condyloma acuminatum
      tissues. Positive apoptotic cells were observed in condyloma acuminatum tissues
      transfected with the HNP1 gene. In addition, the HPV expression was lower in the
      HNP1 treatment tissues as compared to their corresponding control tissues.
      CONCLUSION: The results indicate that HNP1 can directly promote condyloma
      acuminatum cell apoptosis and play an antivirus role in the condyloma acuminatum
      tissue by limiting viral replication. These observations suggest a possible
      application for human HNP1 on condyloma acuminatum therapy.

PMID- 25600883
TI  - Effects of trunk posture in Fowler's position on hemodynamics.
AB  - We speculated that stroke volume would be higher and heart rate would be lower
      when the head and upper trunk were mainly upright in the Fowler's position. We
      therefore analyzed the effects of three trunk postures in Fowler's position on
      heart rate, blood pressure and circulatory volume. Heart rate (HR), blood
      pressure (BP), stroke volume (SV), cardiac output (Q), systemic vascular
      resistance (SVR), ejection time (ET) and pre-ejection period (PEP) were measured
      in 10 healthy male volunteers (mean age +/- SEM, 20.7 +/- 0.5 y; range, 19-23 y)
      while in three trunk postures in Fowler's position. Stroke volume and Q were
      measured using impedance cardiography. The three trunk postures were 30 degrees 
      of lower and upper trunk inclination (WT30 degrees ), 30 degrees  and 60 degrees 
      of lower and upper trunk inclination (UT 60 degrees ), respectively and 60
      degrees  of upper and lower trunk inclination (WT60 degrees ). Both SV and ET
      were significantly higher and HR and PEP were lower at UT60 degrees  than at WT60
      degrees  (p < 0.01) whereas these values did not significantly differ between
      WT30 degrees  and UT60 degrees  (p > 0.05). None of Q, SVR and BP significantly
      differed among the three conditions (p > 0.05). These findings suggested that SV
      and preload are higher when the upper trunk is upright (UT60 degrees ) than when
      the entire trunk is upright (WT60 degrees ) while in Fowler's position. In
      addition, Q might be maintained without increasing HR through vagal withdrawal
      when only the upper trunk is upright in healthy young males in Fowler's position.

PMID- 25600884
TI  - Stimulation of the mesencephalic ventral tegmental area blunts the sensitivity of
      cardiac baroreflex in decerebrate cats.
AB  - We have examined for the first time whether electrical stimulation of the
      mesencephalic ventral tegmental area (VTA) or the substantia nigra (SN) was
      capable of suppressing cardiac baroreflex sensitivity in decerebrate cats. After
      decerebration was performed by electrocoagulation at the precollicular
      premammillary level and inhalation anesthesia was stopped, the animals were able
      to show spontaneous motor activity intermittently. Electrical stimulations of the
      mesencephalic areas (the VTA and SN) for 30s were conducted with a monopolar
      tungsten microelectrode (current intensity of pulse trains, 50-100 MUA;
      frequency, 40-50 Hz; pulse duration, 0.5-1.0 ms), without producing tibial motor
      discharge. Stimulation of the VTA evoked the significant increases in heart rate
      (HR, 12 +/- 2 beats/min) and mean arterial blood pressure (MAP, 12 +/- 3 mm Hg).
      When the baroreflex bradycardia and the slope of the cardiac baroreflex curve
      were examined using a pressor response with brief occlusion of the abdominal
      aorta, the VTA stimulation blunted both the baroreflex bradycardia and the
      maximal slope of the baroreflex MAP-HR curve by 63-74% in the same manner as
      spontaneously-evoked motor activity. In contrast, stimulation of the SN elicited
      no modulation of cardiac baroreflex. It is likely that stimulation of the
      mesencephalic VTA suppresses cardiac baroreflex sensitivity and has the similar
      features of the effects on the cardiac baroreflex function as those during
      spontaneously-evoked motor activity.

PMID- 25600885
TI  - Development and preliminary assessment of a robotic platform for neuroendoscopy
      based on a lightweight robot.
AB  - BACKGROUND: Ventriculostomy is a widely performed neurosurgical procedure; some
      risk factors can be mitigated by computer/robot-assisted approaches. Platforms
      fostering synergistic robot-surgeon integration are pursued, for which
      lightweight robots with compliant controlled joints must be assessed (because
      compliance hampers accuracy). METHODS: We developed a platform encompassing, in
      particular, a lightweight robot and an optical tracker also used to enhance robot
      accuracy. Based on specifications by neurosurgeons, we designed a neuroendoscope
      handling interface and assessed targeting accuracy in a model ventriculostomy
      where the robot was operated both autonomously and in hands-on (i.e. co
      operative) mode. RESULTS: Targeting errors were systematically below the
      procedure accuracy threshold (1 mm); the rms targeting errors were 0.51 and 0.54
      mm for autonomous and hands-on control, respectively. No significant difference
      was observed between the considered control modes. Very positive feedback was
      gathered from neurosurgeons. CONCLUSIONS: Accurate tool targeting under both
      autonomous and hands-on control was achieved.

PMID- 25600886
TI  - Comment on "Discovery of a tetracontinuous, aqueous lyotropic network phase with
      unusual 3D-hexagonal symmetry" by M. Mahanthappa, G. Sorenson and A. Schmitt.
AB  - The article by Sorenson et al. (Soft Matter10, 8229, 2014) reports a novel phase
      formed by gemini surfactants in water, of symmetry P63/mcm and based on a triple
      intergrowth of three identical degree-three networks, known as 3etc(193). This
      phase is the first lyotropic liquid crystalline phase based on the intergrowth of
      a triplet of network- or labyrinth-like hydrophobic domains. We provide here
      results from self-consistent field theory that demonstrate that the same
      morphology is almost stable in standard AB diblock copolymer melts; at the phase
      transition between the double gyroid phase and the hexagonal columnar phase, the
      3etc(193) morphology only incurs a marginal free energy penalty compared to the
      equilibrium phases. Interestingly, the ratio of lattice parameters c/a = 0.955 of
      the 3etc(193) as a diblock morphology is very close to that of the gemini
      surfactant phase and of the related IBN-9 mesoporous silicate phase (Han et al.,
      Nat. Chem.1, 123, 2009). Based on the combination of these results, we
      hypothesise that the 3etc(193) morphology is likely a generic phase in soft
      materials, rather than an oddity. 

PMID- 25600887
TI  - Agronomical and chemical characterisation of Thymbra capitata (L.) Cav. biotypes
      from Sicily, Italy.
AB  - In this study, the agronomical and chemical characterisation of 13 Sicilian
      biotypes of Thymbra capitata (L.) Cav., grown under the same agricultural and
      environmental condition, are reported. The main morpho-productive parameters and
      quali-quantitative profile of essential oils (EOs) were determined. The EOs were
      analysed by gas chromatography-flame ionisation detector and gas chromatography
      mass spectrometry. Hierarchical cluster analysis and principal component analysis
      statistical methods were used to group biotypes according to the EOs chemical
      composition. The EO yield ranged between 4.6 and 8.1 (v/w). A total of 38 EO
      compounds have been identified. The compounds mostly represented were alpha
      pinene, myrcene, alpha-terpinene, p-cymene, gamma-terpinene, borneol, carvacrol
      and beta-caryophyllene. In all biotypes, the carvacrol (67.4-79.5%) was the main
      compound, confirming that T. capitata is a carvacrol chemotype. The results
      showed that all Sicilian Thymbra biotypes have a good adaptation to the climatic
      conditions of the test environment. 

PMID- 25600888
TI  - Two forensic autopsy cases of death due to upper gastrointestinal hemorrhage: a
      comparison of postmortem computed tomography and autopsy findings.
AB  - In this report, we describe two autopsy cases of death due to upper
      gastrointestinal hemorrhage (Case 1: gastric ulcer, Case 2: aortoduodenal
      fistula). Postmortem computed tomography (CT) images from both cases revealed
      pooling of gastric fluid, which contained high attenuation areas, although these
      images also mirrored the different sources of the gastrointestinal hemorrhage.
      Fluid collection was observed in the small intestine for both cases, although the
      high attenuation areas were only remarkable in Case 2. The autopsy in Case 1
      revealed a peptic ulcer, with small vessels exposed on the surface of the ulcer.
      Melena was also observed throughout the intestine, although clotting was only
      observed inside the stomach. The autopsy in Case 2 revealed diffuse massive
      clotting from the stomach to the upper portion of the ileum, which was due to a
      primary aortoduodenal fistula. Given our autopsy findings, the extent of the high
      attenuation areas in the digestive tract during postmortem CT scanning may be
      correlated with the speed of the gastrointestinal hemorrhage before death.
      Carefully evaluating the radiodensity of the gastrointestinal contents during
      postmortem CT scanning may indicate the primary site of the hemorrhage before the
      autopsy, thereby facilitating the accurate identification of the cause of death
      during forensic autopsy. 

PMID- 25600889
TI  - NiO-decorated mesoporous TiO2 flowers for an improved photovoltaic dye sensitized
      solar cell.
AB  - Reducing light-induced e-h recombination is important for a dye sensitized solar
      cell (DSSC); the p-type NiO component in TiO2-NiO nanoparticles was reported to
      significantly decrease charge recombination, but its photovoltaic efficiency
      remains below 4% owing to a small surface area. In this work, we used a one-pot
      self-assembly process to fabricate flower-like mesoporous TiO2 decorated by NiO
      oxides, employing a pluronic polymer P123 as a structure directing and pore
      forming agent. The flower-like porous TiO2-NiO nanoparticles (F-TiO2-NiO NPs),
      possessing a high BET surface of 130 m(2) g(-1), are first used as a photoanode
      in DSSCs. These hybrid nanoparticles, decorated with NiO islands, are beneficial
      for improving photocurrent by increasing dye absorption and suppressing electron
      hole recombination. The optimized F-TiO2-NiO NP anode (10 MUm thick) achieved a
      power conversion efficiency of 8.20%, which is 26% and 47% higher than pristine
      flower-like TiO2 and commercially available P25 anodes, respectively. This
      efficiency is the highest among the reported TiO2-NiO hybrid anodes. 

PMID- 25600890
TI  - In vitro activity of flomoxef and comparators against Escherichia coli,
      Klebsiella pneumoniae and Proteus mirabilis producing extended-spectrum beta
      lactamases in China.
AB  - The objective of this study was to better understand the in vitro activity of
      flomoxef against clinical extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae. A total of 401 ESBL-producing isolates, including 196
      Escherichia coli, 124 Klebsiella pneumoniae and 81 Proteus mirabilis, were
      collected consecutively from 21 hospitals in China in 2013. Minimum inhibitory
      concentrations (MICs) were determined by broth microdilution methods. Phenotypic
      identification of ESBL production was detected as recommended by the Clinical and
      Laboratory Standards Institute (CLSI). ESBL genes were detected by PCR and
      sequencing. Flomoxef, doripenem, meropenem, ertapenem, cefmetazole and
      piperacillin/tazobactam exhibited good activity against ESBL-producing isolates,
      with susceptibility rates >90%. Tigecycline showed good activity against E. coli
      and K. pneumoniae (100% and 97.6%, respectively). Cefotaxime and cefepime showed
      very low activities against ESBL-producing isolates, with susceptibility rates of
      0-0.8% and 1.0-13.6%, respectively. blaCTX-M were the major ESBL genes, with
      occurrence in 99.5% of E. coli, 91.1% of K. pneumoniae and 97.5% of P. mirabilis.
      blaCTX-M-14 was the predominant ESBL gene, detected in 46.9% (188/401) of the
      isolates, followed by blaCTX-M-15 (21.4%), blaCTX-M-55 (17.2%), blaCTX-M-65
      (12.7%) and blaCTX-M-3 (6.7%). Flomoxef exhibited excellent activity against the
      different CTX-M-type ESBL-producing isolates, with MIC50 and MIC90 values of
      0.064-0.125MUg/mL and 0.25-0.5MUg/mL, respectively. Against the isolates solely
      producing CTX-M-14, -15, -55, -3 or -65, flomoxef showed susceptibility rates of
      98.6%, 98.0%, 98.1%, 100.0% and 97.4%, respectively. In conclusion, flomoxef
      showed good activity against ESBL-producing Enterobacteriaceae and may be a
      choice to treat infections caused by these isolates in China. 

PMID- 25600891
TI  - Co-administration of glycyrrhizic acid with the antileishmanial drug sodium
      antimony gluconate (SAG) cures SAG-resistant visceral leishmaniasis.
AB  - Since there are very few affordable antileishmanial drugs available, antimonial
      resistance has crippled antileishmanial therapy, thereby emphasising the need for
      development of novel therapeutic strategies. This study aimed to evaluate the
      antileishmanial role of combined therapy with sodium antimony gluconate (SAG) and
      the triterpenoid glycyrrhizic acid (GA) against infection with SAG-resistant
      Leishmania (GE1F8R). Combination therapy with GA and SAG successfully limited
      infection with SAG-resistant Leishmania in a synergistic manner (fractional
      inhibitory concentration index <1.0). At the same time, mice infected with SAG
      resistant Leishmania and co-treated with GA and SAG exhibited a significant
      reduction in hepatic and splenic parasite burden. In probing the mechanism, it
      was observed that GA treatment suppressed the expression and efflux activity of P
      glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), two
      host ABC transporters responsible for antimony efflux from host cells infected
      with SAG-resistant parasites. This suppression correlated with greater
      intracellular antimony retention during SAG therapy both in vitro and in vivo,
      which was reflected in the reduced parasite load. Furthermore, co-administration
      of GA and SAG induced a shift in the cytokine balance towards a Th1 phenotype by
      augmenting pro-inflammatory cytokines (such as IL-12, IFNgamma and TNFalpha) and
      inducing nitric oxide generation in GE1F8R-infected macrophages as well as GE1F8R
      infected mice. This study aims to provide an affordable leishmanicidal
      alternative to expensive antileishmanial drugs such as miltefosine and
      amphotericin B. Furthermore, this report explores the role of GA as a resistance
      modulator in MRP1- and P-gp-overexpressing conditions. 

PMID- 25600892
TI  - The clinical positioning of telavancin in Europe.
AB  - Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe
      in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant
      Staphylococcus aureus (MRSA), it did not become clinically available until March
      2014. Given the limited clinical experience with telavancin in Europe, this
      review provides an overview of its antimicrobial and clinical activity as well as
      its position among today's antimicrobials, with particular focus on the
      implications of its licensing requirements. Telavancin has potent in vitro
      activity against isolates of Gram-positive pathogens, including MRSA and
      glycopeptide-intermediate S. aureus strains. In addition, at clinically
      attainable doses telavancin inhibits Gram-positive isolates of antibiotic
      resistant strains from biofilm models. The in vitro potency of telavancin has
      been corroborated in the clinical setting. Comparative clinical studies of
      telavancin demonstrate non-inferiority compared with vancomycin in the treatment
      of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin
      treated patients with monomicrobial S. aureus infection, including isolates with
      reduced vancomycin susceptibility. These studies also demonstrate an overall
      similar safety profile for telavancin and vancomycin, although importantly,
      patients with moderate-to-severe renal impairment at baseline are at greater risk
      for mortality with telavancin and this feature must be taken into account when
      selecting patients for its usage. In Europe, telavancin is a useful alternative
      for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there
      are very few alternatives. For example, it should be considered in such patients
      when vancomycin and linezolid are not suitable and where renal function permits. 

PMID- 25600898
TI  - Transparent Reporting of a multivariable prediction model for Individual
      Prognosis or Diagnosis (TRIPOD): the TRIPOD statement.
AB  - Prediction models are developed to aid healthcare providers in estimating the
      probability or risk that a specific disease or condition is present (diagnostic
      models) or that a specific event will occur in the future (prognostic models), to
      inform their decision-making. However, the overwhelming evidence shows that the
      quality of reporting of prediction model studies is poor. Only with full and
      clear reporting of information on all aspects of a prediction model can risk of
      bias and potential usefulness of prediction models be adequately assessed. The
      Transparent Reporting of a multivariable prediction model for Individual
      Prognosis or Diagnosis (TRIPOD) initiative developed a set of recommendations for
      the reporting of studies developing, validating or updating a prediction model,
      whether for diagnostic or prognostic purposes. This article describes how the
      TRIPOD Statement was developed. An extensive list of items based on a review of
      the literature was created, which was reduced after a web-based survey and
      revised during a 3-day meeting in June 2011 with methodologists, healthcare
      professionals and journal editors. The list was refined during several meetings
      of the steering group and in e-mail discussions with the wider group of TRIPOD
      contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study, regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. To aid the
      editorial process and readers of prediction model studies, it is recommended that
      authors include a completed checklist in their submission (also available at
      www.tripod-statement.org). 

PMID- 25600893
TI  - Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control
      study in Italy.
AB  - The aim of this multicentre study was to analyse the characteristics of patients
      with bloodstream infections due to staphylococcal strains resistant to linezolid.
      This was a retrospective case-case-control study of patients hospitalised in
      three large teaching hospitals in Italy. A linezolid-resistant (LIN-R)
      Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp.
      group were compared with control patients to determine the clinical features and
      factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp.
      strains underwent molecular typing. Compared with the LIN-S group, central venous
      catheters were the main source of infection in the LIN-R group. The LIN-R and LIN
      S groups showed a similar incidence of severe sepsis or septic shock, and both
      showed a higher incidence of these compared with the control group. Overall,
      patients in the LIN-R group had a higher 30-day mortality rate. Multivariate
      analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic
      therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at
      least two antibiotics and hospitalisation in the previous 90 days as independent
      risk factors associated with isolation of a LIN-R strain. The G2576T mutation in
      domain V of 23S rRNA was the principal mechanism of resistance; only one strain
      of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together
      with L4 insertion (71GGR72) and L3 substitution (H146Q). LIN-R strains are
      associated with severe impairment of clinical conditions and unfavourable patient
      outcomes. Reinforcement of infection control measures may have an important role
      in preventing these infections. 

PMID- 25600900
TI  - Tissue sodium storage: evidence for kidney-like extrarenal countercurrent
      systems?
AB  - Recent evidence from chemical analysis of tissue electrolyte and water
      composition has shown that body Na(+) content in experimental animals is not
      constant, does not always readily equilibrate with water, and cannot be
      exclusively controlled by the renal blood purification process. Instead, large
      amounts of Na(+) are stored in the skin and in skeletal muscle. Quantitative non
      invasive detection of Na(+) reservoirs with sodium magnetic resonance imaging
      ((23)NaMRI) suggests that this mysterious Na(+) storage is not only an animal
      research curiosity but also exists in humans. In clinical studies, tissue Na(+)
      storage is closely associated with essential hypertension. In animal experiments,
      modulation of reservoir tissue Na(+) content leads to predictable blood pressure
      changes. The available evidence thus suggests that the patho(?)-physiological
      process of Na(+) storage might be of relevance for human health and disease. 

PMID- 25600902
TI  - Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative
      review.
AB  - BACKGROUND: Although vegan-vegetarian diets are increasingly popular, no recent
      systematic reviews on vegan-vegetarian diets in pregnancy exist. OBJECTIVES: To
      review the literature on vegan-vegetarian diets and pregnancy outcomes. SEARCH
      STRATEGY: PubMed, Embase, and the Cochrane library were searched from inception
      to September 2013 for pregnancy and vegan or vegetarian Medical Subject Headings
      (MeSH) and free-text terms. SELECTION CRITERIA: Vegan or vegetarian diets in
      healthy pregnant women. We excluded case reports and papers analysing vegan
      vegetarian diets in poverty and malnutrition. Searching, paper selection, and
      data extraction were performed in duplicate. DATA COLLECTION AND ANALYSIS: The
      high heterogeneity of the studies led to a narrative review. MAIN RESULTS: We
      obtained 262 full texts from 2329 references; 22 selected papers reporting
      maternal-fetal outcomes (13) and dietary deficiencies (nine) met the inclusion
      criteria. None of the studies reported an increase in severe adverse outcomes or
      in major malformations, except one report of increased hypospadias in infants of
      vegetarian mothers. Five studies reported vegetarian mothers had lower
      birthweight babies, yet two studies reported higher birthweights. The duration of
      pregnancy was available in six studies and was similar between vegan-vegetarians
      and omnivores. The nine heterogeneous studies on microelements and vitamins
      suggest vegan-vegetarian women may be at risk of vitamin B12 and iron
      deficiencies. AUTHOR'S CONCLUSIONS: The evidence on vegan-vegetarian diets in
      pregnancy is heterogeneous and scant. The lack of randomised studies prevents us
      from distinguishing the effects of diet from confounding factors. Within these
      limits, vegan-vegetarian diets may be considered safe in pregnancy, provided that
      attention is paid to vitamin and trace element requirements.

PMID- 25600901
TI  - Toll-like receptor 2 mediates vascular contraction and activates RhoA signaling
      in vascular smooth muscle cells from STZ-induced type 1 diabetic rats.
AB  - Increased vascular smooth muscle cell (VSMC) contraction is an early and critical
      contributor to the pathogenesis of vascular dysfunction in diabetes; however,
      knowledge regarding the underlying mechanisms is scarce. Toll-like receptor 2
      (TLR2), a well-known component of the innate immunity, is expressed in VSMC and
      recently has been identified to be systemically activated in diabetes. Whether
      TLR2 is locally activated in the diabetic blood vessels and have effect on
      contraction is not known. In the current study, we examined the role of TLR2 in
      increased vascular contraction in diabetes. Utilizing rat model of type 1
      diabetes (induced by streptozotocin (STZ)), we demonstrated that aortas from STZ
      diabetic rats exhibit increased expression of TLR2 and its adaptor protein,
      myeloid differentiation primary response 88 (MyD88), as well as enhanced protein
      protein interaction between TLR2 and MyD88, suggesting a TLR2 signaling
      activation. Blockade of TLR2 in intact aortas using anti-TLR2 antibody attenuated
      increased vascular contraction in STZ-diabetic rat as assessed by wire myograph.
      Activation of TLR2 by specific ligand in primary aortic VSMC cultures triggered
      activation of RhoA which was exacerbated in cells from STZ-diabetic rats than
      control rats. Activation of RhoA was accompanied by phosphorylation and therefore
      activation of its downstream targets myosin phosphatase target subunit I and
      myosin light chain (markers of VSMC contraction). Taken together, these results
      provide evidence for the role of TLR2 in increased contraction in diabetic blood
      vessels that involves RhoA signaling. Thus, targeting vascular TLR2 offers a
      promising drug target to treat vascular dysfunction in diabetes. 

PMID- 25600903
TI  - Tuberculosis-related stigma leading to an incomplete contact investigation in a
      low-incidence country.
AB  - A contact investigation following a case of infectious tuberculosis (TB) reported
      in a call centre in Milan (Italy) led to the identification of three additional
      cases that had occurred in employees of the same workplace during the previous 5
      years, one of whom was the probable source case. Thirty-three latent infections
      were also identified. At the time of diagnosis, the source case, because of fear
      of stigma related to TB, claimed to be unemployed and a contact investigation was
      not performed in the workplace. Cases were linked through genotyping of
      Mycobacterium tuberculosis. TB stigma has been described frequently, mainly in
      high-incidence settings, and is known to influence health-seeking behaviours and
      treatment adherence. The findings in this report highlight that TB-associated
      stigma may also lead to incomplete contact investigations. Little is known about
      the causes and impact of TB-related stigma in low-incidence countries and this
      warrants further exploration. Research is also needed to evaluate the
      effectiveness of specific interviewing techniques and training interventions for
      staff in reducing feelings of stigma in TB patients. Finally, the outbreak
      emphasizes the importance of integrating routine contact investigations with
      genotyping. 

PMID- 25600904
TI  - Technical player profiles related to the physical fitness of young female
      volleyball players predict team performance.
AB  - AIM: This study is divided into three sequential stages: identification of
      fitness and game performance profiles (individual player performance), an
      assessment of the relationship between these profiles, and an assessment of the
      relationship between individual player profiles and team performance during play
      (in championship performance). METHODS: The overall study sample comprised 525
      (19 teams) female volleyball players aged 12-16 years and a subsample (N.=43)
      used to examine study aims one and two was selected from overall sample.
      Anthropometric, fitness and individual player performance (actual game) data were
      collected in the subsample. These data were analyzed through clustering methods,
      ANOVA and independence chi-square test. Then, we investigated whether the
      proportion of players with the highest individual player performance profile
      might predict a team's results in the championship. Cluster analysis identified
      three volleyball fitness profiles (high, medium, and low) and two individual
      player performance profiles (high and low). RESULTS: The results showed a
      relationship between both types of profile (fitness and individual player
      performance). Then, linear regression revealed a moderate relationship between
      the number of players with a high volleyball fitness profile and a team's results
      in the championship (R2=0.23). CONCLUSION: The current study findings may enable
      coaches and trainers to manage training programs more efficiently in order to
      obtain tailor-made training, identify volleyball-specific physical fitness
      training requirements and reach better results during competitions.

PMID- 25600905
TI  - Effect of L-carnitine supplementation in comparison with moderate aerobic
      training on serum inflammatory parameters in healthy obese women.
AB  - AIM: Obesity is an important worldwide public health problem and considered a
      disease of chronic low-grade inflammation. The aim of this study was to evaluate
      the effect of L-carnitine supplementation in comparison with moderate aerobic
      exercise training on serum inflammatory parameters in healthy obese women.
      METHODS: In this double-blind randomized controlled clinical trial, 44 obese
      women were randomly assigned to 4 groups (N.=11) as follows: 1: L-carnitine
      supplementation (2 g/day) (CAR), 2: aerobic training + placebo (EXR+PLA), 3: L
      carnitine supplementation + aerobic training (CAR+EXR) and 4: placebo (PLA). All
      intervention periods were eight weeks and subjects of aerobic training groups
      underwent 8-week aerobic training protocol (3 sessions a week [24 sessions]).
      Body Mass Index, daily dietary intake and serum free L-carnitine, IL-6, high
      sensitivity C-reactive protein (Hs-CRP) and IL-10 levels of subjects were
      measured before and after interventions. RESULTS: Interventions had no
      significant effects on body weight, BMI, daily dietary intake and serum IL-10
      levels of subjects in all groups. Serum free L-carnitine concentration increased
      significantly after interventions in CAR and CAR+EXR groups. Significant
      decreases of IL-6 were observed in EXR+PLA and CAR+EXR groups compared with
      placebo group. L-carnitine supplementation plus aerobic training led to
      significant decrease of serum Hs-CRP levels in CAR+EXR group compared with
      baseline values. CONCLUSION: L-carnitine supplementation did not affect serum IL
      6, Hs-CRP and IL-10 levels in obese women. Aerobic training alone or in
      combination with L-carnitine had favorable effect on serum Il-6 and Hs-CRP levels
      as markers of inflammation in studied subjects.

PMID- 25600906
TI  - Cardiac dimensions and function in female handball players.
AB  - AIM: Long-term intensive endurance training leads to increased left ventricular
      mass and increased left ventricular end-diastolic and left atrial end-systolic
      diameters. Different types of sports tend to give rise to distinct morphological
      forms of the athlete's heart. However, the sport-specific aspects have not been
      fully investigated in female athletes. The purpose of the present study was to
      investigate differences in left and right cardiac dimensions, cardiac volumes,
      and systolic and diastolic function in elite female handball players compared to
      sedentary controls. METHODS: A cross-sectional study of 33 elite female handball
      players was compared to 33 matched sedentary controls. Mean age was 21.5+/-2
      years. The subjects underwent echocardiography examinations, both 2-dimensional
      (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified
      using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were
      also evaluated. All cardiac dimensions and volumes were adjusted for body surface
      area (BSA). RESULTS: Left atrium and left ventricle volumes were significantly
      (P<0.001) larger in elite female handball players compared with sedentary
      controls. Even right atrium area as well as right ventricular end-diastolic and
      end-systolic area were significantly (P<0.001) larger in elite female handball
      players. Significant differences were observed in three out of five systolic
      parameters. Most diastolic function parameters did not differ between the two
      groups. CONCLUSION: The findings from the present study suggest that similar
      cardiac remodeling takes place in elite female handball players as it does in
      athletes pursuing endurance or team game sports.

PMID- 25600907
TI  - Graphene-modified nanostructured vanadium pentoxide hybrids with extraordinary
      electrochemical performance for Li-ion batteries.
AB  - The long-standing issues of low intrinsic electronic conductivity, slow lithium
      ion diffusion and irreversible phase transitions on deep discharge prevent the
      high specific capacity/energy (443 mAh g(-1) and 1,550 Wh kg(-1)) vanadium
      pentoxide from being used as the cathode material in practical battery
      applications. Here we develop a method to incorporate graphene sheets into
      vanadium pentoxide nanoribbons via the sol-gel process. The resulting graphene
      modified nanostructured vanadium pentoxide hybrids contain only 2 wt. % graphene,
      yet exhibits extraordinary electrochemical performance: a specific capacity of
      438 mAh g(-1), approaching the theoretical value (443 mAh g(-1)), a long
      cyclability and significantly enhanced rate capability. Such performance is the
      result of the combined effects of the graphene on structural stability,
      electronic conduction, vanadium redox reaction and lithium-ion diffusion
      supported by various experimental studies. This method provides a new avenue to
      create nanostructured metal oxide/graphene materials for advanced battery
      applications. 

PMID- 25600908
TI  - Targeting the invasive phenotype of cisplatin-resistant non-small cell lung
      cancer cells by a novel histone deacetylase inhibitor.
AB  - Non-Small Cell Lung Cancer (NSCLC) remains an aggressive and fatal disease with
      low responsiveness to chemotherapy, frequent drug resistance development and
      metastatic behavior. Platinum-based therapy is the standard of care for NSCLC
      with limited benefits. Since epigenetic alterations have been implicated in the
      aggressive behavior of lung cancer, the purpose of the present study was to
      examine the capability of the pan-histone deacetylase inhibitor SAHA and of
      ST3595, a novel hydroxamate-based compound, to interfere with the proliferative
      and invasive potential of NSCLC cells. We used two NSCLC cell lines (H460 and
      A549) and the cisplatin-resistant variants (H460/Pt and A549/Pt), to mimic a
      frequent clinical condition. The resistant models exhibited increased invasive
      properties as compared to parental cells, features associated with a wide
      modulation of the level of angiogenesis- and invasion-related factors in the cell
      conditioned media. The levels of urokinase-type plasminogen activator, IL-8, and
      macrophage migration inhibitory factor were increased in the conditioned media
      from both H460/Pt and A549/Pt cells. SAHA and ST3595 induced a strong inhibition
      of cell invasive properties, which was more marked after ST3595 exposure. Both
      HDAC inhibitors up-regulated the metastasis suppressor KiSS1 at the mRNA level.
      Forced expression of KiSS1 significantly decreased the invasive capability of
      drug-resistant cells. ST3595 displayed an anti-metastatic effect in tumors
      associated with decreased of phosphorylation of Src. Our data indicate that HDAC
      inhibitors are effective in NSCLC cell systems. The ability of ST3595 to
      counteract the invasive potential of resistant cells through mechanisms involving
      KiSS1 is an interesting novel finding. 

PMID- 25600909
TI  - Intestinal interleukin-10 mobilization as a contributor to the anti-arthritis
      effect of orally administered madecassoside: a unique action mode of saponin
      compounds with poor bioavailability.
AB  - Madecassoside, a triterpenoid saponin present in Centella asiatica herbs with
      extremely low bioavailability, possesses excellent anti-rheumatoid arthritis
      property after oral administration. Such a disconnection between poor
      pharmacokinetic property and undoubted bioactivity also exists in many other
      herbal medicines. However, there is no reasonable explanation for this phenomenon
      to date. Here we showed that orally administered madecassoside displayed marked
      therapeutic effect on collagen-induced arthritis (CIA) in rats, which was
      accompanied by a systemic downregulation of inflammatory cytokines and an
      upregulation of anti-inflammatory cytokine IL-10. In vitro assays demonstrated
      that neither madecassoside nor its main metabolite madecassic acid could directly
      interfere with the secretion of inflammatory cytokines and IL-10. Intraperitoneal
      injection of madecassoside or madecassic acid was absent of significant effects
      on CIA progression, which further excluded the possibility of systemic action and
      highlighted the indispensable role of intestinal tracts. Notably, madecassoside
      could dramatically enhance the secretion of IL-10 from the small intestine of CIA
      rats probably through increasing the number of Foxp3(+) T lymphocytes in the
      lamina propria. In conclusion, madecassoside displays anti-arthritis property not
      by absorption into blood or by its metabolite, but through an intestine-dependent
      manner. The action can be mediated by, at least partially, the mobilization of IL
      10 that originates from small intestines. 

PMID- 25600910
TI  - Escherichia coli-induced temporal and differential secretion of heat-shock
      protein 70 and interleukin-1beta by human fetal membranes in a two-compartment
      culture system.
AB  - INTRODUCTION: Escherichia coli is recognized as an etiological bacteria
      associated with chorioamnionitis and the preterm premature rupture of fetal
      membranes. This pathological condition induces pro-inflammatory cytokines and
      degradative metalloproteinases, which are considered biological markers secreted
      in an acute stage of infection. Heat-shock proteins (HSPs) are an important
      component of the innate immunity response and are found in different pathological
      conditions. They have not been previously measured in human fetal membranes in
      response to infectious conditions. We hypothesized that the choriodecidual tissue
      and amniotic epithelium secreted temporal and differential Hsp-60, Hsp-70, and
      interleukin (IL)-1beta mediated by E. coli infection. METHODS: Fetal membranes
      were mounted in a two-compartment culture system and infected with two passes of
      live E. coli at different doses (102, 104, 105, and 106 colony-forming units
      (CFU)/mL) and intervals of incubation (3, 6, and 24 h). The culture medium was
      collected, and Hsp-60, Hsp-70, and IL-1beta were assessed using the enzyme-linked
      immunosorbent assay (ELISA) method. RESULTS: After 3 and 6 h of infection, E.
      coli induced an increase in Hsp-70 secretion in the choriodecidual tissue.
      However, after 24 h of incubation, Hsp-70 was downregulated and we observed an
      increase in IL-1beta secretion. By contrast, E. coli induced a lower Hsp-60
      secretion in the amnion compared to Hsp-70. DISCUSSION: Human fetal membranes
      responded actively to E. coli infection, with an increase in Hsp-70 during the
      first hours of infection. After 24 h, there was an increase in the liberation of
      IL-1beta.

PMID- 25600912
TI  - Typing of Propionibacterium acnes: a review of methods and comparative analysis.
AB  - Propionibacterium acnes is a major commensal of the human skin. However, it is
      also the pathogen responsible for acne vulgaris and other diseases, such as
      medical-device infections. Strains of Propionibacterium acnes have long been
      classified into several different types. Recently, typing systems for this
      bacterium have taken on an increased importance as different types of P. acnes
      have been found to be associated with different disease states, including acne.
      Genetic approaches based on individual or multiple genes have classified P. acnes
      into types, which have been supported by the sequencing of nearly 100 P. acnes
      genomes. These types have distinct genetic, transcriptomic and proteomic
      differences. Additionally, they may have different immune response profiles.
      Taken together, these factors may account for the different disease associations
      of P. acnes types.

PMID- 25600913
TI  - First neonatal organ donation in the UK.

PMID- 25600915
TI  - Investigations on contribution of glial inwardly-rectifying K(+) current to
      membrane potential and ion flux: an experimental and theoretical study.
AB  - The inwardly rectifying K(+) current [IK(IR)] allows large inward K(+) currents
      at potentials negative to K(+) equilibrium potential (EK) and it becomes small
      outward K(+) currents at those positive to EK. How changes of such currents
      enriched in glial cells can influence the functions of glial cell, neurons, or
      both is not clearly defined, although mutations of Kir4.1 channels have been
      demonstrated to cause serious neurological disorders. In this study, we
      identified the presence of IK(IR) in human glioma cells (U373 and U87 cells). The
      amplitude of IK(IR) in U373 cells was subject to inhibition by amitriptyline,
      arecoline, or BaCl2. The activity of inwardly rectifying K(+) channels was also
      clearly detected, and single-channel conductance of these channels was calculated
      to be around 23 pS. Moreover, based on a simulation model derived from neuron
      glial interaction mediated by ion flux, we further found out that incorporation
      of glial IK(IR) conductance into the model can significantly contribute to
      regulation of extracellular K(+) concentrations and glial resting potential,
      particularly during high-frequency stimulation. Glial cells and neurons can
      mutually modulate their expression of ion channels through K(+) ions released
      into the extracellular space. It is thus anticipated that glial IK(IR) may be a
      potential target utilized to influence the activity of neuronal and glial cells
      as well as their interaction. 

PMID- 25600911
TI  - Strain hypothesis of Toxoplasma gondii infection on the outcome of human
      diseases.
AB  - The intracellular protozoan Toxoplasma gondii is an exceptionally successful food
      and waterborne parasite that infects approximately 1 billion people worldwide.
      Genotyping of T. gondii isolates from all continents revealed a complex
      population structure. Recent research supports the notion that T. gondii genotype
      may be associated with disease severity. Here, we (1) discuss molecular and
      serological approaches for designation of T. gondii strain type, (2) overview the
      literatures on the association of T. gondii strain type and the outcome of human
      disease and (3) explore possible mechanisms underlying these strain-specific
      pathology and severity of human toxoplasmosis. Although no final conclusions can
      be drawn, it is clear that virulent strains (e.g. strains containing type I or
      atypical alleles) are significantly more often associated with increased
      frequency and severity of human toxoplasmosis. The significance of highly
      virulent strains can cause severe diseases in immunocompetent patients and might
      implicated in brain disorders such as schizophrenia should led to reconsideration
      of toxoplasmosis. Further studies that combine parasite strain typing and human
      factor analysis (e.g. immune status and genetic background) are required for
      better understanding of human susceptibility or resistance to toxoplasmosis. 

PMID- 25600914
TI  - Ca(2+) movement and apoptosis induced by deltamethrin in Madin-Darby canine
      kidney canine renal tubular cells.
AB  - This study explored the effect of deltamethrin, a pesticide, on free Ca(2+)
      concentration [Ca(2+)]i, viability, and apoptosis in Madin-Darby canine kidney
      (MDCK) canine renal tubular cells. Deltamethrin at concentrations between 10MUM
      and 40MUM evoked [Ca(2+)]i rises in a concentration-dependent manner. The Ca(2+)
      entry was inhibited by nifedipine, econazole, phorbol 12-myristate 13-acetate,
      and SKF96365. Treatment with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5
      di-tert-butylhydroquinone (BHQ) in a Ca(2+)-free medium abolished deltamethrin
      induced [Ca(2+)]i rise. Treatment with deltamethrin also abolished BHQ-induced
      [Ca(2+)]i rise. Inhibition of phospholipase C (PLC) activity with U73122
      abolished deltamethrin-evoked [Ca(2+)]i rise. Deltamethrin killed cells at 30
      60MUM in a concentration-dependent manner. The cytotoxic effect of deltamethrin
      was not reversed by prechelating cytosolic Ca(2+) with the acetoxymethyl ester of
      1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Annexin V/propidium
      iodide staining data suggest that 30-50MUM deltamethrin induced apoptosis.
      Together, in MDCK renal tubular cells, deltamethrin induced [Ca(2+)]i rises that
      involved Ca(2+) entry through protein kinase C-mediated store-operated Ca(2+)
      channels, and PLC-dependent Ca(2+) release from the endoplasmic reticulum.
      Deltamethrin also induced Ca(2+)-independent cell death that might involve
      apoptosis. 

PMID- 25600916
TI  - Antigen-extracted xenogeneic cancellous bone graft with recombinant human bone
      morphogenetic protein-2 enhances bone regeneration in repair of mandibular defect
      in rabbits.
AB  - The effects of a large-piece of xenogeneic bone that was separated from healthy
      pigs as a scaffold for the repair of a mandibular defect was investigated, and
      the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked
      with recombinant human bone morphogenetic protein-2 (rhBMP-2) in bone defect
      repair was assessed. Mandibular defects were created in 48 New Zealand rabbits,
      and the animals were randomly divided into four groups, in which the mandibular
      defects were grafted with AXCB, AXCB soaked with rhBMP-2, and autograft bone, or
      left blank. An equal number of animals from each group were classified into three
      time points (4, 8, and 12 weeks) after surgery for gross pathological
      observation, hematoxylin and eosin (H and E) staining, radiographic examination,
      and bone density measurement. H and E staining revealed that the area percentage
      of bone regeneration in the group of the AXCB/rhBMP-2 graft was 27.72 +/- 4.68,
      53.90 +/- 21.92, and 77.35 +/- 9.83 at 4 weeks, 8 weeks, and 12 weeks,
      respectively. These results were better than those of the autogenous bone graft,
      suggesting that the group of the AXCB/rhBMP-2 graft achieved a good osteogenic
      effect. With regard to the AXCB graft without rhBMP-2, the area percentage of
      bone regeneration was only 14.03 +/- 5.02, 28.49 +/- 11.35, and 53.90 +/- 21.92.
      Therefore, the osteogenic effect of the AXCB/rhBMP-2 graft was demonstrated to
      have the best effect. In the group of the AXCB/rhBMP-2 graft, the area percentage
      of bone regeneration increased, and the implanted materials were gradually
      degraded and replaced by autogenous bone regeneration over time. We conclude that
      the AXCB graft soaked with rhBMP-2 showed good osteogenic effect in the repair of
      bone defects and good biocompatibility. AXCB serves as a good carrier of rhBMP-2,
      which promotes bone formation. 

PMID- 25600917
TI  - Clinical performance of a new hepatitis B surface antigen quantitative assay with
      automatic dilution.
AB  - Hepatitis B virus surface antigen (HBsAg) levels reflect disease status and can
      predict the clinical response to antiviral treatment; however, the emergence of
      HBsAg mutant strains has become a challenge. The Abbott HBsAg quantification
      assay provides enhanced detection of HBsAg and HBsAg mutants. We aimed to
      evaluate the performance of the Abbott HBsAg quantification assay with automatic
      sample dilutions (shortened as automatic Architect assay), compared with the
      Abbott HBsAg quantification assay with manual sample dilutions (shortened as
      manual Architect assay) and the Roche HBsAg quantification assay with automatic
      sample dilutions (shortened as Elecsys). A total of 130 sera samples obtained
      from 87 hepatitis B virus (HBV)-infected patients were collected to assess the
      correlation between the automatic and manual Architect assays. Among the 87
      patients, 41 provided 42 sera samples to confirm the linearity and
      reproducibility of the automatic Architect assay, and find out the correlation
      among the Elecsys and two Architect assays. The coefficients of variation (0.44
      9.53%) and R(2) = 0.996-1, which were both determined using values obtained from
      the automatic Architect assay, showed good reproducibility and linearity. Results
      of the two Architect assays demonstrated a feasible correlation (n = 130 samples;
      R = 0.898, p < 0.01). With regard to subgroups, correlations between the two
      Architect assays were better in the hepatitis B e antigen (HBeAg)-negative group
      (HBeAg-negative group vs. HBeAg-positive group: R = 0.885 vs. R = 0.865, both p <
      0.01) and low HBV DNA group (low DNA group vs. high DNA group: R = 0.886 vs. R =
      0.844, both p < 0.01). Significant correlations were also found between the
      results of the Elecsys and Architect assays (R > 0.93 in all cases). In
      conclusion, the correlation between the automatic and manual dilution Architect
      assays was feasible, particularly in the HBeAg-negative and low DNA groups. With
      lower labor costs and less human error than the manual version, the Abbott
      automatic dilution Architect assay provided a good clinical performance with
      regard to the HBsAg levels.

PMID- 25600918
TI  - Noncontrast computed tomography can predict the outcome of shockwave lithotripsy
      via accurate stone measurement and abdominal fat distribution determination.
AB  - Urolithiasis is a common disease of the urinary system. Extracorporeal shockwave
      lithotripsy (SWL) has become one of the standard treatments for renal and
      ureteral stones; however, the success rates range widely and failure of stone
      disintegration may cause additional outlay, alternative procedures, and even
      complications. We used the data available from noncontrast abdominal computed
      tomography (NCCT) to evaluate the impact of stone parameters and abdominal fat
      distribution on calculus-free rates following SWL. We retrospectively reviewed
      328 patients who had urinary stones and had undergone SWL from August 2012 to
      August 2013. All of them received pre-SWL NCCT; 1 month after SWL, radiography
      was arranged to evaluate the condition of the fragments. These patients were
      classified into stone-free group and residual stone group. Unenhanced computed
      tomography variables, including stone attenuation, abdominal fat area, and skin
      to-stone distance (SSD) were analyzed. In all, 197 (60%) were classified as stone
      free and 132 (40%) as having residual stone. The mean ages were 49.35 +/- 13.22
      years and 55.32 +/- 13.52 years, respectively. On univariate analysis, age, stone
      size, stone surface area, stone attenuation, SSD, total fat area (TFA), abdominal
      circumference, serum creatinine, and the severity of hydronephrosis revealed
      statistical significance between these two groups. From multivariate logistic
      regression analysis, the independent parameters impacting SWL outcomes were stone
      size, stone attenuation, TFA, and serum creatinine. [Adjusted odds ratios and
      (95% confidence intervals): 9.49 (3.72-24.20), 2.25 (1.22-4.14), 2.20 (1.10
      4.40), and 2.89 (1.35-6.21) respectively, all p < 0.05]. In the present study,
      stone size, stone attenuation, TFA and serum creatinine were four independent
      predictors for stone-free rates after SWL. These findings suggest that
      pretreatment NCCT may predict the outcomes after SWL. Consequently, we can use
      these predictors for selecting the optimal treatment for patients with urinary
      stones. 

PMID- 25600919
TI  - Severe pneumonia in mycophenolate mofetil combined with low-dose corticosteroids
      treated patients with immunoglobulin A nephropathy.
AB  - The tolerance of mycophenolate mofetil (MMF; Shanghai Roche, China) in Lee
      Classes III, IV, and V immunoglobulin A nephropathy (IgAN) remains unclear. This
      article reports nine cases of severe pneumonia (SP), including pneumocystis
      pneumonia (PCP) and cytomegalovirus (CMV) pneumonia, and its risk factors in MMF
      plus low-dose corticosteroid-treated patients with Lee Classes III, IV, and V
      IgAN. Fifty-three patients with IgAN were included in this single-center study.
      The treatment regimen was MMF (1-1.5 g/d) plus low-dose corticosteroids (0.5
      mg/kg/d). SP was defined as diffuse bilateral lung infiltrate with respiratory
      failure. PCP was diagnosed by detecting the organisms in the sputum and
      bronchoalveolar lavage. CMV infection was diagnosed through serum screening for
      CMV-IgG and IgM antibodies and CMV-DNA testing by a real-time polymerase chain
      reaction assay. The risk factors of SP were analyzed. Nine cases (16.9%) of SP
      occurred in this study. All SP developed at approximately the 10(th)-14(th) week
      after the initiation of the regimen: PCP was diagnosed in four cases and CMV
      infection in two cases. Renal function impairing was more serious in patients
      with SP than in those without SP, as evidenced by estimated glomerular filtration
      rate (p = 0.019) and serum creatinine level (p = 0.016). Six of the nine SPs
      occurred in MMP plus low-dose methylprednisolone group, which was statistically
      higher than that in the MMF plus low-dose prednisone group (p = 0.000). The
      incidence of SP in this study was 16.9%. Chronically impaired renal function and
      the use of methylprednisolone may be the risk factors for SP.

PMID- 25600920
TI  - Dimensional approach to symptom factors of major depressive disorder in Koreans,
      using the Brief Psychiatric Rating Scale: the Clinical Research Center for
      Depression of South Korea study.
AB  - Although major depressive disorder (MDD) has a variety of symptoms beyond the
      affective dimensions, the factor structure and contents of comprehensive
      psychiatric symptoms of this disorder have rarely been explored using the 18-item
      Brief Psychiatric Rating Scale (BPRS). We aimed to identify the factor structure
      of the 18-item BPRS in Korean MDD patients. A total of 258 MDD patients were
      recruited from a multicenter sample of the Clinical Research Center for
      Depression of South Korea study. Psychometric scales were used to assess overall
      psychiatric symptoms (BPRS), depression (Hamilton Depression Rating Scale),
      anxiety (Hamilton Anxiety Rating Scale), global severity (Clinical Global
      Impression of Severity Scale), suicidal ideation (Scale for Suicide Ideation),
      functioning (Social and Occupational Functioning Assessment Scale), and quality
      of life (World Health Organization Quality of Life Assessment-abbreviated
      version). Common factor analysis with oblique rotation was used to yield factor
      structure. A four-factor structure was designed and interpreted by the symptom
      dimensions to reflect mood disturbance, positive symptoms/apathy, bipolarity, and
      thought distortion/mannerism. These individual factors were also significantly
      correlated with clinical variables. The findings of this study support the view
      that the BPRS may be a promising measuring tool for the initial assessment of MDD
      patients. In addition, the four-factor structure of the BPRS may be useful in
      understanding the mood and psychotic characteristics of these patients. 

PMID- 25600921
TI  - Primary cerebellopontine angle lymphoma.

PMID- 25600922
TI  - Fatal outcome of persistent/recurrent Cushing's disease after pituitary surgery.

PMID- 25600923
TI  - Severe complication of catatonia in a young patient with Hashimoto's
      encephalopathy comorbid with Cornelia de Lange syndrome.

PMID- 25600924
TI  - Growth inhibition and altered gene transcript levels in earthworms (Eisenia
      fetida) exposed to 2,2',4,4'-tetrabromodiphenyl ether.
AB  - The toxic effects of the ubiquitous pollutant 2,2',4,4'-tetrabromodiphenyl ether
      (BDE-47) on the earthworm Eisenia fetida were assessed by determining growth
      inhibition and gene transcript levels of superoxide dismutase (SOD), catalase
      (CAT), glutathione transferase (GST), and transcriptional changes of the stress
      response gene (heat-shock protein 70 [Hsp70]). Somatic growth and growth
      inhibition rates in all BDE-47-treated groups were significantly different from
      those of the controls. The SOD gene transcripts were upregulated at all exposure
      doses and reached the maximum at the concentration of 400 mg/kg dry weight (dw)
      (3.84-fold, P < 0.01), which protected earthworms from oxidative stresses.
      However, downregulation of CAT and Hsp70 was present in all exposure doses and
      reached to the minimum at concentrations of 400 mg/kg dw (0.07-fold, P < 0.01 and
      0.06-fold, P < 0.01, respectively). Upregulation of GST gene transcript level
      presented significant changes at concentrations of 10 (2.69-fold, P < 0.05) and
      100 mg/kg dw (2.55-fold, P < 0.05). SOD maintained a dynamic balance to
      upregulate SOD expression to eliminate superoxide radicals in all dosage
      treatments, but downregulation of CAT decreased the ability to eliminate hydrogen
      peroxide. These changes could result in biochemical and physiological
      disturbances in earthworms.

PMID- 25600925
TI  - A software system to collect expert relevance ratings of medical record items for
      specific clinical tasks.
AB  - Development of task-specific electronic medical record (EMR) searches and user
      interfaces has the potential to improve the efficiency and safety of health care
      while curbing rising costs. The development of such tools must be data-driven and
      guided by a strong understanding of practitioner information requirements with
      respect to specific clinical tasks or scenarios. To acquire this important data,
      this paper describes a model by which expert practitioners are leveraged to
      identify which components of the medical record are most relevant to a specific
      clinical task. We also describe the computer system that was created to
      efficiently implement this model of data gathering. The system extracts medical
      record data from the EMR of patients matching a given clinical scenario, de
      identifies the data, breaks the data up into separate medical record items (eg,
      radiology reports, operative notes, laboratory results, etc), presents each
      individual medical record item to experts under the hypothetical of the given
      clinical scenario, and records the experts' ratings regarding the relevance of
      each medical record item to that specific clinical scenario or task. After an
      iterative process of data collection, these expert relevance ratings can then be
      pooled and used to design point-of-care EMR searches and user interfaces tailored
      to the task-specific needs of practitioners. 

PMID- 25600926
TI  - Congenital epulis of the newborn: difficult to diagnose but easy to treat. A case
      of unusual size.
AB  - The epulis or giant cell granuloma is a benign tumor of the connective tissue of
      the gingival mucosa frequent in an advanced period of life but much more rare in
      its congenital form. We present the case of a female newborn, otherwise healthy,
      presenting with a giant swelling protruding from her mouth and originating from
      upper left alveolar ridge. The size of the mass has created great anxiety in
      parents and pediatricians, however this clinical presentation suggested us a
      diagnosis of congenital epulis with a differential diagnosis of teratoma. We
      perform surgical resection of the mass under general anesthesia, through
      diathermy. There wasn't blood loss and postoperative recovery was uneventful. A
      definite diagnosis of giant congenital epulis was disclosed by histopathological
      and immunohistochemical analysis. Although it has not been yet clarified the
      etiology of this tumor and the role of hormonal influences on its appearance and
      development and despite have been reported cases of spontaneous regression, the
      treatment of choice is the early surgical excision. Nevertheless, particularly in
      the small centers, due to the rarity and large size of presentation, the
      diagnosis is often delayed or wrong, exposing so the newborn parents to useless
      days of waiting and anxiety In our opinion all pediatricians and surgeons should
      be aware of this malformation and of its simple, safe and effective surgical
      treatment, considering the excellent prognosis of this rare disease.

PMID- 25600927
TI  - Bordetella trematum in chronic ulcers: report on two cases and review of the
      literature.
AB  - We report on two new cases Bordetella trematum in chronic ulcers. Literature
      shows that this species is infrequently isolated from clinical samples. Only a
      few cases have been reported so far. B. trematum may be underdiagnosed because of
      its problematic identification. Today, MALDI-TOF MS allows for an accurate
      discrimination of these bacteria. Overall, B. trematum was typically associated
      with severe skin and soft tissue infections, particularly in diabetic patients.
      The intrinsic resistance to some antibiotics commonly used to treat these
      infections makes the isolation of B. trematum significant. 

PMID- 25600928
TI  - Lack of awareness in both patients and physicians contributes to a high rate of
      late presentation in a South West German HIV patient cohort.
AB  - PURPOSE: To assess rate of late presentation with HIV in Southwestern Germany and
      to identify patient characteristics correlated with CD4 nadir. METHODS: Patients
      with primary diagnosis who presented to one of ten participating clinics rated on
      knowledge and behavior towards HIV testing on a self-developed questionnaire,
      whereas clinical data was assessed by the physician. RESULTS: 161 patients were
      included. Risk factors were homosexual (59.5 %) or heterosexual contacts (26.8
      %), drug use (2.0 %), migration (3.9 %), or others (7.8 %). 63.5 % had a CD4 T
      cell count < 350/ul. 52.5, 17.4, and 31.1 % were diagnosed in CDC stadium A, B or
      C, respectively. 209 disease episodes were reported, from whom 83.7 % had led to
      the diagnosis of HIV. 75.2 and 68.3 % said to have been well-informed about ways
      of transmission and testing offerings, respectively, and 20.4 % admitted to have
      psychologically repressed the possibility of being infected. 48 patients rated
      their personal behavioral risk as "high" or "very high". Of these, however, only
      ten had performed at test in the precedent year. Performing a regression
      analysis, younger age and previous testing were correlated with a higher CD4 T
      cell nadir (p = 0.005, and 0.018, resp.). CONCLUSION: The rate of late
      presentation in this region was even higher compared to national or European
      surveys. Most infected patients perceived to have had only a low risk. Several
      disease episodes did not lead to the initiation of HIV testing by the physician.

PMID- 25600929
TI  - Severe neurologic syndrome associated with Middle East respiratory syndrome
      corona virus (MERS-CoV).
AB  - BACKGROUND: Since the identification of the first case of infection with the
      Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June
      2012, the number of laboratory-confirmed cases has exceeded 941 cases globally,
      of which 347 died. The disease presents as severe respiratory infection often
      with shock, acute kidney injury, and coagulopathy. Recently, we observed three
      cases who presented with neurologic symptoms. These are so far the first reported
      cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was
      retrospectively collected from three patients admitted with MERS-CoV infection to
      Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were
      managed separately in three different wards prior to their admission to ICU.
      FINDING: The three patients presented with severe neurologic syndrome which
      included altered level of consciousness ranging from confusion to coma, ataxia,
      and focal motor deficit. Brain MRI revealed striking changes characterized by
      widespread, bilateral hyperintense lesions on T2-weighted imaging within the
      white matter and subcortical areas of the frontal, temporal, and parietal lobes,
      the basal ganglia, and corpus callosum. None of the lesions showed gadolinium
      enhancement. INTERPRETATION: CNS involvement should be considered in patients
      with MERS-CoV and progressive neurological disease, and further elucidation of
      the pathophysiology of this virus is needed.

PMID- 25600930
TI  - Subcutaneous abscess due to the basidiomycete Phellinus mori in a patient with
      chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD), a primary immunodeficiency caused by
      impaired phagocyte killing of intracellular pathogens, is characterized by
      recurrent, life-threatening, bacterial and fungal infections. As a result of
      improvements in microbiologic culture and identification techniques, a number of
      unique filamentous fungi have been reported as significant pathogens in patients
      with CGD. We report a case of subcutaneous basidiomycete Phellinus mori infection
      in a patient with CGD. To the best of our knowledge, this is the first reported
      case of human infection by this fungus. The causative fungus was identified on
      the basis of its morphological characteristics and nucleotide sequence on the
      internal transcribed spacer region of the ribosomal RNA gene. This is the fifth
      case report of filamentous basidiomycetes infecting a patient with CGD; all of
      these cases have been caused by Phellinus species. We highlight the importance of
      recognizing filamentous basidiomycetes Phellinus species as possible agents of
      non-Aspergillus fungal infections in patients with CGD. 

PMID- 25600931
TI  - Effect of cotrimoxazole prophylaxis on malaria occurrence in HIV-infected
      patients on antiretroviral therapy in sub-Saharan Africa.
AB  - OBJECTIVE: To systematically review the evidence on the effect of cotrimoxazole
      (CTX) on malaria in HIV-positive individuals on antiretroviral therapy (ART).
      METHODS: Web of Science, PubMed and MEDLINE, EMBASE, Global Health and Cochrane
      Library databases were searched using terms for malaria, HIV and CTX. Studies
      meeting the inclusion criteria were reviewed and assessed for bias and
      confounding. RESULTS: Six studies (in Uganda, Kenya, Malawi, Zambia and Zimbabwe)
      had relevant data on the effect of CTX on malaria in patients on ART: four were
      observational cohort studies (OCS) and two were randomised controlled trials
      (RCTs); two were in children and one in women only. Samples sizes ranged from 265
      to 2200 patients. Four studies compared patients on ART and CTX with patients on
      ART alone; 2 (RCTs) found a significant increase in smear-positive malaria on ART
      alone: (IRR 32.5 CI = 8.6-275.0 and HR 2.2 CI = 1.5-3.3) and 2 (OCS) reported
      fewer parasitaemia episodes on CTX and ART (OR 0.85 CI = 0.65-1.11 and 3.6% vs.
      2.4% of samples P = 0.14). One OCS found a 76% (95% CI = 63-84%) vs. 83% (95% CI
      = 74-89%) reduction in malaria incidence in children on CTX and ART vs. on CTX
      only, when both were compared with HIV-negative children. The other reported a
      64% reduction in malaria incidence after adding ART to CTX (RR = 0.36, 95% CI =
      0.18-0.74). The 2 RCTs were unblinded. Only one study reported adherence to CTX
      and ART, and only two controlled for baseline CD4 count. CONCLUSION: Few studies
      have investigated the effect of CTX on malaria in patients on ART. Their findings
      suggest that CTX is protective against malaria even among patients on ART.

PMID- 25600932
TI  - A dynamically coupled allosteric network underlies binding cooperativity in Src
      kinase.
AB  - Protein tyrosine kinases are attractive drug targets because many human diseases
      are associated with the deregulation of kinase activity. However, how the
      catalytic kinase domain integrates different signals and switches from an active
      to an inactive conformation remains incompletely understood. Here we identify an
      allosteric network of dynamically coupled amino acids in Src kinase that connects
      regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants
      (ATP and peptide substrates) bind with negative cooperativity to Src kinase while
      products (ADP and phosphopeptide) bind with positive cooperativity. We confirm
      the molecular details of the signal relay through the allosteric network by
      biochemical studies. Experiments on two additional protein tyrosine kinases
      indicate that the allosteric network may be largely conserved among these
      enzymes. Our work provides new insights into the regulation of protein tyrosine
      kinases and establishes a potential conduit by which resistance mutations to ATP
      competitive kinase inhibitors can affect their activity. 

PMID- 25600933
TI  - Stability of (13) C-Urea Breath Test Samples Over Time in the Diagnosis of
      Helicobacter pylori.
AB  - BACKGROUND: The accuracy and repeatability of breath test in the diagnosis of
      Helicobacter pylori infection have not been adequately investigated. Although it
      has been shown that storage for long periods does not affect the analysis
      results, no data are available on the effect of repetitive testing. In this
      study, our aim was to evaluate the repeatability of the analyses of breath
      samples at room temperature. METHODS: A total of 202 positive breath samples were
      collected in duplicates, before and after administration of 75 mg (13) C- urea
      dissolved in 100 ml of orange juice. Breath test results were expressed as delta
      (13) CO2 . The cut-off value was 3.5 parts per thousand. Each sample was analyzed
      in a mass spectrometer 7, 14, 21, and 28 days after collection. The accuracy
      calculation was based on the comparison of the delta (13) CO2 obtained in the
      three consecutive weeks following the first test run to the delta (13) CO2
      obtained in the first test run. RESULTS: Two hundred (99%), 197 (97.52%), and 196
      (97%) of the 202 samples tested positive in the second, third, and fourth test
      runs, respectively. The accuracy of the delta (13) CO2 was 98.6%, 99.2%, and
      96.7% in the three consecutive runs, respectively. CONCLUSION: Short-term storage
      of 1 month does not affect sample stability or the results of (13) C-urea breath
      tests in up to three consecutive repeats.

PMID- 25600934
TI  - Morphogens, modeling and patterning the neural tube: an interview with James
      Briscoe.
AB  - James Briscoe has a BSc in Microbiology and Virology (from the University of
      Warwick, UK) and a PhD in Molecular and Cellular Biology (from the Imperial
      Cancer Research Fund, London, now Cancer Research UK). He started working on the
      development of the neural tube in the lab of Tom Jessel as a postdoctoral fellow,
      establishing that there was graded sonic hedgehog signaling in the ventral neural
      tube. He is currently a group leader and Head of Division in Developmental
      Biology at the MRC National Institute for Medical Research (which will become
      part of the Francis Crick Institute in April 2015). He is working to understand
      the molecular and cellular mechanisms of graded signaling in the vertebrate
      neural tube.We interviewed him about the development of ideas on morphogenetic
      gradients and his own work on modeling the development of the neural tube for our
      series on modeling in biology. 

PMID- 25600935
TI  - Reduced mandibular range of motion in Duchenne Muscular Dystrophy: predictive
      factors.
AB  - Patients with Duchenne muscular dystrophy (DMD) experience negative effects upon
      feeding and oral health. We aimed to determine whether the mandibular range of
      motion in DMD is impaired and to explore predictive factors for the active
      maximum mouth opening (aMMO). 23 patients with DMD (mean age 16.7 +/- 7.7 years)
      and 23 controls were assessed using a questionnaire about mandibular function and
      impairments. All participants underwent a clinical examination of the masticatory
      system, including measurement of mandibular range of motion and variables related
      to mandibular movements. In all patients, quantitative ultrasound of the
      digastric muscle and the geniohyoid muscle and the motor function measure (MFM)
      scale were performed. The patients were divided into early and late ambulatory
      stage (AS), early non-ambulatory stage (ENAS) and late non-ambulatory stage
      (LNAS). All mandibular movements were reduced in the patient group (P < 0.001)
      compared to the controls. Reduction in the aMMO (<40 mm) was found in 26% of the
      total patient group. LNAS patients had significantly smaller mandibular movements
      compared to AS and ENAS (P < 0.05). Multiple linear regression analysis for aMMO
      revealed a positive correlation with the body height and disease progression,
      with MFM total score as the strongest independent risk factor (R(2) = 0.71).
      Mandibular movements in DMD are significantly reduced and become more hampered
      with loss of motor function, including the sitting position, arm function, and
      neck and head control. We suggest that measurement of the aMMO becomes a part of
      routine care of patients with DMD.

PMID- 25600936
TI  - High-temperature supercapacitor with a proton-conducting metal pyrophosphate
      electrolyte.
AB  - Expanding the range of supercapacitor operation to temperatures above 100 
      degrees C is important because this would enable capacitors to operate under the
      severe conditions required for next-generation energy storage devices. In this
      study, we address this challenge by the fabrication of a solid-state
      supercapacitor with a proton-conducting Sn(0.95)Al(0.05)H(0.05)P(2)O(7) (SAPO)
      polytetrafluoroethylene (PTFE) composite electrolyte and a highly condensed H3PO4
      electrode ionomer. At a temperature of 200  degrees C, the SAPO-PTFE electrolyte
      exhibits a high proton conductivity of 0.02 S cm(-1) and a wide withstanding
      voltage range of +/- 2 V. The H3PO4 ionomer also has good wettability with
      micropore-rich activated carbon, which realizes a capacitance of 210 F g(-1) at
      200  degrees C. The resulting supercapacitor exhibits an energy density of 32 Wh
      kg(-1) at 3 A g(-1) and stable cyclability after 7000 cycles from room
      temperature to 150  degrees C.

PMID- 25600938
TI  - Serum endothelin 1 levels before, during and after mechanochemical endovenous
      ablation with foam and surgical correction of incompetent great saphenous veins.

PMID- 25600937
TI  - Arabidopsis thaliana MSI4/FVE associates with members of a novel family of plant
      specific PWWP/RRM domain proteins.
AB  - AtMSI4/FVE/ACG1, one of five Arabidopsis thaliana genes encoding MSI1-like
      proteins, helps determine plant growth and development (including control of
      flowering), as well as responses to certain biotic and abiotic stresses. We
      reasoned that the product of this gene, AtMSI4, acts through protein partners,
      which we have co-immunopurified with AtMSI4 from A. thaliana suspension culture
      cells and identified by liquid chromatography-mass spectrometry (LC-MS). Many of
      the proteins associated with AtMSI4 have distinct RNA recognition motif (RRM)
      domains, which we determined to be responsible for association with AtMSI4; and
      most of the associated RRM domain proteins also contain PWWP domains that are
      specific to plants. We propose these novel ATMSI4-associated proteins help form
      nucleoprotein complexes that determine pleiotropic functional properties of
      AtMSI4/FVE/ACG1 involving plant development and responses to stress. 

PMID- 25600939
TI  - Takotsubo syndrome due to 4-fluoroamphetamine.

PMID- 25600940
TI  - Electronic structure engineering of Cu2O film/ZnO nanorods array all-oxide p-n
      heterostructure for enhanced photoelectrochemical property and self-powered
      biosensing application.
AB  - We have engineered the electronic structure at the interface between Cu2O and ZnO
      nanorods (NRs) array, through adjusting the carrier concentration of Cu2O. The
      electrodeposition of Cu2O at pH 11 acquired the highest carrier concentration,
      resulting in the largest interfacial electric field between Cu2O and ZnO, which
      finally led to the highest separation efficiency of photogenerated charge
      carriers. The optimized Cu2O/ZnO NRs array p-n heterostructures exhibited
      enhanced PEC performance, such as elevated photocurrent and photoconversion
      efficiency, as well as excellent sensing performance for the sensitive detection
      of glutathione (GSH) in PBS buffer even at applied bias of 0 V which made the
      device self-powered. Besides, the favorable selectivity, high reproducibility and
      extremely wide detection range, make such heterostructure a promising candidate
      for PEC biosensing applications, probably for the extended field of PEC water
      splitting or other solar photovoltaic beacons. 

PMID- 25600941
TI  - Enabling systematic, harmonised and large-scale biofilms data computation: the
      Biofilms Experiment Workbench.
AB  - BACKGROUND AND OBJECTIVE: Biofilms are receiving increasing attention from the
      biomedical community. Biofilm-like growth within human body is considered one of
      the key microbial strategies to augment resistance and persistence during
      infectious processes. The Biofilms Experiment Workbench is a novel software
      workbench for the operation and analysis of biofilms experimental data. The goal
      is to promote the interchange and comparison of data among laboratories,
      providing systematic, harmonised and large-scale data computation. METHODS: The
      workbench was developed with AIBench, an open-source Java desktop application
      framework for scientific software development in the domain of translational
      biomedicine. Implementation favours free and open-source third-parties, such as
      the R statistical package, and reaches for the Web services of the BiofOmics
      database to enable public experiment deposition. RESULTS: First, we summarise the
      novel, free, open, XML-based interchange format for encoding biofilms
      experimental data. Then, we describe the execution of common scenarios of
      operation with the new workbench, such as the creation of new experiments, the
      importation of data from Excel spreadsheets, the computation of analytical
      results, the on-demand and highly customised construction of Web publishable
      reports, and the comparison of results between laboratories. CONCLUSIONS: A
      considerable and varied amount of biofilms data is being generated, and there is
      a critical need to develop bioinformatics tools that expedite the interchange and
      comparison of microbiological and clinical results among laboratories. We propose
      a simple, open-source software infrastructure which is effective, extensible and
      easy to understand. The workbench is freely available for non-commercial use at
      http://sing.ei.uvigo.es/bew under LGPL license.

PMID- 25600942
TI  - Identification of three potent hydroxyproline O-galactosyltransferases in
      Arabidopsis.
AB  - Arabinogalactan proteins (AGPs) are plant-specific extracellular glycoproteins
      implicated in a variety of processes during growth and development. AGP
      biosynthesis involves O-galactosylation of hydroxyproline (Hyp) residues followed
      by a stepwise elongation of the complex sugar chains. However, functionally
      dominant Hyp O-galactosyltransferases, such that their disruption produces
      phenocopies of AGP-deficient mutants, remain to be identified. Here, we purified
      and identified three potent Hyp O-galactosyltransferases, HPGT1, HPGT2 and HPGT3,
      from Arabidopsis microsomal fractions. Loss-of-function analysis indicated that
      approximately 90% of the endogenous Hyp O-galactosylation activity is
      attributable to these three enzymes. AGP14 expressed in the triple mutant
      migrated much faster on SDS-PAGE than when expressed in wild-type, confirming a
      considerable decrease in levels of glycosylation of AGPs in the mutant. Loss-of
      function mutant plants exhibited a pleiotropic phenotype of longer lateral roots,
      longer root hairs, radial expansion of the cells in the root tip, small leaves,
      shorter inflorescence stems, reduced fertility and shorter siliques. Our findings
      provide genetic evidence that Hyp-linked arabinogalactan polysaccharide chains
      are critical for AGP function and clues to how arabinogalactan moieties of AGPs
      contribute to cell-to-cell communication during plant growth and development. 

PMID- 25600944
TI  - Functional Gene Networks: R/Bioc package to generate and analyse gene networks
      derived from functional enrichment and clustering.
AB  - Functional Gene Networks (FGNet) is an R/Bioconductor package that generates gene
      networks derived from the results of functional enrichment analysis (FEA) and
      annotation clustering. The sets of genes enriched with specific biological terms
      (obtained from a FEA platform) are transformed into a network by establishing
      links between genes based on common functional annotations and common clusters.
      The network provides a new view of FEA results revealing gene modules with
      similar functions and genes that are related to multiple functions. In addition
      to building the functional network, FGNet analyses the similarity between the
      groups of genes and provides a distance heatmap and a bipartite network of
      functionally overlapping genes. The application includes an interface to directly
      perform FEA queries using different external tools: DAVID, GeneTerm Linker, TopGO
      or GAGE; and a graphical interface to facilitate the use.

PMID- 25600943
TI  - "I Created Something New with Something that Had Died": Photo-Narratives of
      Positive Transformation Among Women with HIV.
AB  - A dearth of research describes the strengths of women living with HIV (WLH), yet
      understanding these strengths can promote women's well-being and healthy
      behavior. This analysis explores positive life transformations among WLH through
      photo-stories. WLH (N = 30) from three U.S. cities participated in a pilot
      photovoice project to tell their story of HIV. The project included three group
      meetings, an individual interview, and a public exhibit. Using qualitative
      strategies of theme and narrative analysis we identified positive transformations
      in women's photo-stories. Participants were African American (83 %) and low
      income (83 %). Women described four major positive transitions in their lives
      including transformations related to healthfulness, spirituality, self
      acceptance, and confidence. Despite challenges, WLH experience positive
      transformation and growth experiences. Understanding these transformative changes
      can shed light on women's motivation to make healthy life changes and thus frame
      strengths-based interventions for WLH. Photovoice itself is a potential strategy
      to promote WLH's strengths and health.

PMID- 25600945
TI  - WALTZ-DB: a benchmark database of amyloidogenic hexapeptides.
AB  - Accurate prediction of amyloid-forming amino acid sequences remains an important
      challenge. We here present an online database that provides open access to the
      largest set of experimentally characterized amyloid forming hexapeptides. To this
      end, we expanded our previous set of 280 hexapeptides used to develop the Waltz
      algorithm with 89 peptides from literature review and by systematic experimental
      characterisation of the aggregation of 720 hexapeptides by transmission electron
      microscopy, dye binding and Fourier transform infrared spectroscopy. This brings
      the total number of experimentally characterized hexapeptides in the WALTZ-DB
      database to 1089, of which 244 are annotated as positive for amyloid formation.

PMID- 25600946
TI  - drexplorer: A tool to explore dose-response relationships and drug-drug
      interactions.
AB  - MOTIVATION: Nonlinear dose-response models are primary tools for estimating the
      potency [e.g. half-maximum inhibitory concentration (IC) known as IC50] of anti
      cancer drugs. We present drexplorer software, which enables biologists to
      evaluate replicate reproducibility, detect outlier data points, fit different
      models, select the best model, estimate IC values at different percentiles and
      assess drug-drug interactions. drexplorer serves as a computation engine within
      the R environment and a graphical interface for users who do not have programming
      backgrounds.

PMID- 25600947
TI  - Deep profiling of multitube flow cytometry data.
AB  - MOTIVATION: Deep profiling the phenotypic landscape of tissues using high
      throughput flow cytometry (FCM) can provide important new insights into the
      interplay of cells in both healthy and diseased tissue. But often, especially in
      clinical settings, the cytometer cannot measure all the desired markers in a
      single aliquot. In these cases, tissue is separated into independently analysed
      samples, leaving a need to electronically recombine these to increase
      dimensionality. Nearest-neighbour (NN) based imputation fulfils this need but can
      produce artificial subpopulations. Clustering-based NNs can reduce these, but
      requires prior domain knowledge to be able to parameterize the clustering, so is
      unsuited to discovery settings. RESULTS: We present flowBin, a parameterization
      free method for combining multitube FCM data into a higher-dimensional form
      suitable for deep profiling and discovery. FlowBin allocates cells to bins
      defined by the common markers across tubes in a multitube experiment, then
      computes aggregate expression for each bin within each tube, to create a matrix
      of expression of all markers assayed in each tube. We show, using simulated
      multitube data, that flowType analysis of flowBin output reproduces the results
      of that same analysis on the original data for cell types of >10% abundance. We
      used flowBin in conjunction with classifiers to distinguish normal from cancerous
      cells. We used flowBin together with flowType and RchyOptimyx to profile the
      immunophenotypic landscape of NPM1-mutated acute myeloid leukemia, and present a
      series of novel cell types associated with that mutation.

PMID- 25600949
TI  - Comment on "Nasal bone length: prenasal thickness ratio: a strong 2D ultrasound
      marker for Down syndrome".

PMID- 25600950
TI  - Cyclopropanation using flow-generated diazo compounds.
AB  - We have devised a room temperature process for the cyclopropanation of electron
      poor olefins using unstabilised diazo compounds, generated under continuous flow
      conditions. This protocol was applied to a wide range of different diazo species
      to generate functionalised cyclopropanes which are valuable 3D building blocks. 

PMID- 25600948
TI  - Iron homeostasis: a new job for macrophages in adipose tissue?
AB  - Elevated serum ferritin and increased cellular iron concentrations are risk
      factors for diabetes; however, the etiology of this association is unclear.
      Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as
      the immune cells resident in these tissues, may be involved. Recent studies
      demonstrate that the polarization status of macrophages has important relevance
      to their iron-handling capabilities. Furthermore, a subset of macrophages in AT
      have elevated iron concentrations and a gene expression profile indicative of
      iron handling, a capacity diminished in obesity. Because iron overload in
      adipocytes increases systemic insulin resistance, iron handling by AT macrophages
      may have relevance not only to adipocyte iron stores but also to local and
      systemic insulin sensitivity. 

PMID- 25600951
TI  - Segmental cholangiectasia clinically worrisome for cholangiocarcinoma: comparison
      with recurrent pyogenic cholangitis.
AB  - The aim of this study was to review the clinical, radiographic, and pathologic
      features of cases of benign segmental cholangiectasia in non-Asian US patients
      with clinical concern for cholangiocarcinoma and compare these features with
      cases of recurrent pyogenic cholangitis (RPC) in Asian patients. A total of 10
      non-Asian US patients with benign segmental cholangiectasia were included in this
      study. Nine of them underwent partial hepatic resection due to cholangiographic
      findings of segmental cholangiectasia with mural thickening and/or proximal
      biliary stricture. One was found to have markedly dilated and thickened
      intrahepatic bile ducts at the time of autopsy. Clinical and radiographic
      findings were reviewed. Elastin stains and immunostains for immunoglobulin G4,
      cluster of differentiation (CD1a), and Langerin were performed. Six comparison
      cases of RPC in Asian US patients were also examined. Histologic examination of
      resection specimens revealed markedly dilated large intrahepatic bile ducts with
      variable degrees of mural fibrosis, periductal gland hyperplasia, inflammation,
      and liver parenchymal atrophy. These changes were not associated with a ductular
      reaction. There was no evidence of biliary dysplasia or biliary cirrhosis in any
      cases. No gross or microscopic feature definitively separated the Asian from non
      Asian patients. The etiology of this disorder in non-Asian US patients is
      unclear. It does not appear to represent a localized variant of Caroli disease or
      primary sclerosing cholangitis. The high degree of similarity shared by these
      cases and classic RPC suggests a common pathogenic mechanism, although the
      pathologic features tend to be less well developed in the cases from the non
      Asian US patients. 

PMID- 25600952
TI  - Toward a modern era in clinical prediction: the TRIPOD statement for reporting
      prediction models.

PMID- 25600953
TI  - Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic
      Kidney Disease at Various Levels of Kidney Function.
AB  - BACKGROUND: A recent study showed that tolvaptan, a vasopressin V2 receptor
      antagonist, decreased total kidney volume (TKV) growth and estimated glomerular
      filtration rate (GFR) loss in autosomal dominant polycystic kidney disease
      (ADPKD) with creatinine clearance>=60mL/min. The aim of our study was to
      determine whether the renal hemodynamic effects and pharmacodynamic efficacy of
      tolvaptan in ADPKD are dependent on GFR. STUDY DESIGN: Clinical trial with
      comparisons before and after treatment. SETTING & PARTICIPANTS: Patients with
      ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital
      setting. INTERVENTION: Participants were studied at baseline and after 3 weeks of
      treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60,
      90, and 120mg/d in weeks 1, 2, and 3, respectively). OUTCOMES: Change in markers
      for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine
      volume, and plasma copeptin) and kidney injury (TKV and kidney injury
      biomarkers). MEASUREMENTS: GFR was measured by (125)I-iothalamate clearance; TKV,
      by magnetic resonance imaging; biomarker excretion, by enzyme-linked
      immunosorbent assay; and osmolality, by freezing point depression. RESULTS: In 27
      participants (52% men; aged 46+/-10 years; mGFR, 69+/-39mL/min; TKV, 2.15 [IQR,
      1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and
      free-water clearance and a decrease in urine osmolality, TKV, and kidney injury
      marker excretion. Changes in urine volume and osmolality with treatment were less
      in participants with lower baseline mGFRs (both P<0.01). However, change in
      fractional free-water clearance was greater at lower baseline mGFRs (P=0.001),
      suggesting that participants with decreased GFRs responded more to tolvaptan per
      functioning nephron. LIMITATIONS: Limited sample size, no control group.
      CONCLUSIONS: In patients with ADPKD with decreased kidney function, response to
      tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for
      fractional free-water clearance. This latter finding suggests that patients with
      ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as
      has been observed for patients with preserved GFRs.

PMID- 25600954
TI  - A 3-year hygiene and safety monitoring of a meat processing plant which uses raw
      materials of global origin.
AB  - A systematic approach in monitoring the hygiene of a meat processing plant using
      classical microbiological analyses combined with molecular characterization tools
      may assist in the safety of the final products. This study aimed: (i) to evaluate
      the total hygiene level and, (ii) to monitor and characterize the occurrence and
      spread of Salmonella spp. and Listeria monocytogenes in the environment and the
      final products of a meat industry that processes meat of global origin. In total,
      2541 samples from the processing environment, the raw materials, and the final
      products were collected from a Greek meat industry in the period 2011-2013. All
      samples were subjected to enumeration of total viable counts (TVC), Escherichia
      coli (EC) and total coliforms (TCC) and the detection of Salmonella spp., while
      709 of these samples were also analyzed for the presence L. monocytogenes.
      Pathogen isolates were serotyped and further characterized for their antibiotic
      resistance and subtyped by PFGE. Raw materials were identified as the primary
      source of contamination, while improper handling might have also favored the
      proliferation of the initial microbial load. The occurrence of Salmonella spp.
      and L. monocytogenes reached 5.5% and 26.9%, respectively. Various (apparent)
      cross-contamination or persistence trends were deduced based on PFGE analysis
      results. Salmonella isolates showed wide variation in their innate antibiotic
      resistance, contrary to L. monocytogenes ones, which were found susceptible to
      all antibiotics except for cefotaxime. The results emphasize the biodiversity of
      foodborne pathogens in a meat industry and may be used by meat processors to
      understand the spread of pathogens in the processing environment, as well as to
      assist the Food Business Operator (FBO) in establishing effective criteria for
      selection of raw materials and in improving meat safety and quality. This
      approach can limit the increase of microbial contamination during the processing
      steps observed in our study as well as the cross contamination of meat products. 

PMID- 25600955
TI  - Relationships among medication adherence, insight, and neurocognition in chronic
      schizophrenia.
AB  - AIMS: In order to improve long-term prognosis in schizophrenia, enhancing
      medication adherence is essential. The aim of this study was thus to identify the
      association between medication non-adherence and possible risk factors in a large
      sample of patients with chronic schizophrenia. METHODS: One hundred and four
      patients with schizophrenia with a disease duration of over 10 years were
      enrolled in this cross-sectional study. The subjects were assessed with the Scale
      to Assess Unawareness of Mental Disease-Korean version, the Korean version of the
      Medication Adherence Rating Scale, a neurocognition battery designed for this
      study, and the Positive and Negative Symptoms Scale. An anova and multiple
      regression models were conducted to identify the correlations among variables and
      the factors that contribute to medication adherence. RESULTS: The adherence score
      measured on the Korean version of the Medication Adherence Rating Scale was 7.60
      +/- 2.12; 88 (84.62%) patients were categorized as well-adherent and 16 (15.38%)
      as poorly adherent to their medication. Patients with good insight were more
      likely to maintain their medication (P = 0.0005), and better executive function
      was associated with increased medication adherence (P = 0.0008). Furthermore,
      fewer depressive symptoms were associated with good medication adherence (P =
      0.0304). CONCLUSIONS: This study is the first in the Republic of Korea to
      identify the relationship between medication adherence, insight, and
      neurocognition in a large sample of patients with chronic schizophrenia. These
      results could be used to establish a strategy for improving the prognosis of
      chronic schizophrenia.

PMID- 25600957
TI  - Clinical decision support system to enhance quality control of spirometry using
      information and communication technologies.
AB  - BACKGROUND: We recently demonstrated that quality of spirometry in primary care
      could markedly improve with remote offline support from specialized
      professionals. It is hypothesized that implementation of automatic online
      assessment of quality of spirometry using information and communication
      technologies may significantly enhance the potential for extensive deployment of
      a high quality spirometry program in integrated care settings. OBJECTIVE: The
      objective of the study was to elaborate and validate a Clinical Decision Support
      System (CDSS) for automatic online quality assessment of spirometry. METHODS: The
      CDSS was done through a three step process including: (1) identification of
      optimal sampling frequency; (2) iterations to build-up an initial version using
      the 24 standard spirometry curves recommended by the American Thoracic Society;
      and (3) iterations to refine the CDSS using 270 curves from 90 patients. In each
      of these steps the results were checked against one expert. Finally, 778
      spirometry curves from 291 patients were analyzed for validation purposes.
      RESULTS: The CDSS generated appropriate online classification and certification
      in 685/778 (88.1%) of spirometry testing, with 96% sensitivity and 95%
      specificity. CONCLUSIONS: Consequently, only 93/778 (11.9%) of spirometry testing
      required offline remote classification by an expert, indicating a potential
      positive role of the CDSS in the deployment of a high quality spirometry program
      in an integrated care setting.

PMID- 25600956
TI  - Identifying Predictors of Longitudinal Decline in the Level of Medical Care
      Received by Adult Survivors of Childhood Cancer: A Report from the Childhood
      Cancer Survivor Study.
AB  - OBJECTIVES: Characterize longitudinal changes in the use of medical care in adult
      survivors of childhood cancer. DATA SOURCES: The Childhood Cancer Survivor Study,
      a retrospective cohort study of 5+ year survivors of childhood cancer. STUDY
      DESIGN: Medical care was assessed at entry into the cohort (baseline) and at most
      recent questionnaire completion. Care at each time point was classified as no
      care, general care, or survivor-focused care. DATA COLLECTION: There were 6,176
      eligible survivors. Multivariable models evaluated risk factors for reporting
      survivor-focused care or general medical care at baseline and no care at follow
      up; and survivor-focused care at baseline and general care at follow-up.
      PRINCIPAL FINDINGS: Males (RR, 2.3; 95 percent CI 1.8-2.9), earning <$20,000/year
      (RR, 1.6; 95 percent CI 1.2-2.3) or <= high school education (RR, 2.5; 95 percent
      CI 1.6-3.8 and RR 2.0; 95 percent CI 1.5-2.7 for <high school and high school,
      respectively) were associated with no care at follow-up. Survivors with severe or
      life-threatening conditions at baseline (RR 0.5; 95 percent CI 0.3-0.6) were less
      likely to report no care at follow-up. CONCLUSIONS: While the incidence of late
      effects increases over time for survivors, the likelihood of receiving survivor
      focused care decreases for vulnerable populations.

PMID- 25600958
TI  - Damage effect of interleukin (IL)-23 on oxygen-glucose-deprived cells of the
      neurovascular unit via IL-23 receptor.
AB  - Interleukin-23/interleukin-23 receptor (IL-23/IL-23R) has been implicated in many
      inflammatory diseases. Previous research mainly focused on its ability to induce
      IL-17 production from T cells. However, few studies have investigated its role in
      cerebral ischemic injury. The aim of our study was to explore the potential
      effect of IL-23 on cells of the neurovascular unit (NVU) under an oxygen-glucose
      deprivation (OGD) condition and the role of IL-23R in IL-23-mediated effect. OGD
      of primary cells of the NVU and permanent middle cerebral artery occlusion
      (pMCAO) were used to produce experimental stroke in vitro and in vivo,
      respectively. IL-23 and IL-23R were detected by immunohistochemistry and western
      blot in pMCAO mice. Metabolic viability of cultured cells was assessed by MTT
      assay. The cell-associated proteins (Bcl-2, AQP4 and ET-1) were determined by
      western blot and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence
      staining and western blot were used to detect the IL-23R expression. The results
      showed that the expression of IL-23/IL-23R was elevated in pMCAO mice. IL-23
      could aggravate neuron damage, astrocyte swelling, and further impair the
      integrity of blood-brain barrier induced by OGD. In addition, the effect of IL-23
      on cells of the NVU is mediated by IL-23R and is likely IL-23R-expression-level
      dependent. However, there are no such biological properties for the IL-23p19
      subunit alone. Our study provides the first evidence that IL-23 has a toxic
      effect on cells of the NVU under OGD stress, which is mediated by IL-23R. These
      results not only help us better understand the role of IL-23/IL-23R in brain
      ischemia, but also provide a potential therapeutic target in stroke. 

PMID- 25600959
TI  - Forkhead box protein P3 (Foxp3) expression serves as an early chronic
      inflammation marker of squamous cell differentiation and aggressive pathology of
      urothelial carcinomas in neurological patients.
AB  - OBJECTIVE: To establish whether the expression of forkhead box protein P3 (Foxp3)
      provides specific diagnostic information about neurological patients with
      urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: UCB tissue
      samples from neurological patients were retrieved and compared with control
      samples. The expression of Foxp3 was analysed via immunohistochemistry of
      microarray tissue sections. The correlation between Foxp3 expression,
      histological parameters and tumour stage was assessed. RESULTS: Overall, 20 UCB
      tissue samples and 20 others without UCB from neurological patients, and 46 UCB
      tissue samples from non-neurological patients were analysed. The distribution of
      pT of UCB in the neurological patients was as follows: one low-grade pTa (5%),
      three high-grade pTa (15%), three pT1(15%), one pT2(5%), seven pT3(35%) and five
      pT4(25%). Squamous cell differentiation was seen in nine UCB samples (45%). Foxp3
      expression was detected in tumour tissues, including one pTa high grade, one pT1,
      one pT2, five pT3 and five pT4 tumours. Foxp3 was expressed in 11/13 muscle
      invasive tumours. All tumours displaying squamous cell differentiation expressed
      Foxp3. Foxp3 was not expressed in the pT3 tumours that displayed sarcomatoid and
      micropapillary properties. Among the bladder samples without UCB from
      neurological patients, no expression of Foxp3 was observed. Among the UCB samples
      from the non-neurological patients, only seven displayed squamous cell
      differentiation. All tumours that displayed squamous cell differentiation
      expressed Foxp3, including one pTa high grade, four pT3 and two pT4 tumours.
      Other tumours displaying urothelial differentiation did not express Foxp3. The
      expression of Foxp3 correlated to squamous cell differentiation in neurological
      (P = 0.004) and non-neurological UCB tissue (P < 0.001). In neurological, but not
      non-neurological UCB tissue, the expression of Foxp3 correlated with the muscle
      invasive stage (P = 0.022). CONCLUSIONS: Elevated expression of Foxp3 appears to
      be a characteristic of neurological patients presenting with aggressive UCB and
      squamous cell differentiation. Targeting Foxp3 may represent a novel strategy to
      improve anti-tumour immunotherapy for UCB.

PMID- 25600960
TI  - Cartilage-specific ablation of XBP1 signaling in mouse results in a
      chondrodysplasia characterized by reduced chondrocyte proliferation and delayed
      cartilage maturation and mineralization.
AB  - OBJECTIVE: To investigate the in vivo role of the IRE1/XBP1 unfolded protein
      response (UPR) signaling pathway in cartilage. DESIGN: Xbp1(flox/flox).Col2a1-Cre
      mice (Xbp1(CartDeltaEx2)), in which XBP1 activity is ablated specifically from
      cartilage, were analyzed histomorphometrically by Alizarin red/Alcian blue
      skeletal preparations and X-rays to examine overall bone growth, histological
      stains to measure growth plate zone length, chondrocyte organization, and
      mineralization, and immunofluorescence for collagen II, collagen X, and IHH.
      Bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) analyses were used to measure chondrocyte proliferation and cell
      death, respectively. Chondrocyte cultures and microdissected growth plate zones
      were analyzed for expression profiling of chondrocyte proliferation or
      endoplasmic reticulum (ER) stress markers by Quantitative PCR (qPCR), and of Xbp1
      mRNA splicing by RT-PCR to monitor IRE1 activation. RESULTS: Xbp1(CartDeltaEx2)
      displayed a chondrodysplasia involving dysregulated chondrocyte proliferation,
      growth plate hypertrophic zone shortening, and IRE1 hyperactivation in
      chondrocytes. Deposition of collagens II and X in the Xbp1(CartDeltaEx2) growth
      plate cartilage indicated that XBP1 is not required for matrix protein deposition
      or chondrocyte hypertrophy. Analyses of mid-gestation long bones revealed delayed
      ossification in Xbp1(CartDeltaEx2) embryos. The rate of chondrocyte cell death
      was not significantly altered, and only minimal alterations in the expression of
      key markers of chondrocyte proliferation were observed in the Xbp1(CartDeltaEx2)
      growth plate. IRE1 hyperactivation occurred in Xbp1(CartDeltaEx2) chondrocytes
      but was not sufficient to induce regulated IRE1-dependent decay (RIDD) or a
      classical UPR. CONCLUSION: Our work suggests roles for XBP1 in regulating
      chondrocyte proliferation and the timing of mineralization during endochondral
      ossification, findings which have implications for both skeletal development and
      disease.

PMID- 25600961
TI  - Enhanced beta-adrenergic cardiac reserve in Trpm4-/- mice with ischaemic heart
      failure.
AB  - AIMS: Heart failure (HF) is a complex syndrome characterized by critically
      reduced cardiac contractility and function. We have shown previously that
      Transient Receptor Potential Melastatin 4 protein (TRPM4) functions as a Ca(2+)
      activated non-selective cation channel and constitutes a novel regulator of
      ventricular contractility. In healthy Trpm4-deficient (Trpm4(-/-)) mice, we
      observed increased cardiac contractile function after beta-adrenergic
      stimulation. In the current study, cardiac performance was examined in wild-type
      (WT) and Trpm4(-/-) mice with severe ischaemic HF. METHODS AND RESULTS:
      Myocardial infarction (MI) was induced in WT and Trpm4(-/-) C57Bl6/N mice by
      ligation of the left anterior descending artery. During the first week after MI,
      mortality was higher in WT mice. Both groups showed similar infarct-typical ECG
      patterns during follow-up period. After 10 weeks, reduced ejection fraction and
      severe dilatation, determined by cardiac MRI, confirmed the development of HF in
      both genotypes. In vivo pressure-conductance analysis revealed no differences in
      cardiac contractility in basal conditions. However, during beta-adrenergic
      stimulation, cardiac performance was significantly different between WT and
      Trpm4(-/-) mice. In contrast to increasing contractility in Trpm4(-/-) mice, WT
      mice showed a deteriorated cardiac performance. Also 30% of WT animals died
      during isoprenaline infusion vs. no Trpm4(-/-) mice. Infarct size, determined
      post mortem, was equal in WT and Trpm4(-/-) hearts. CONCLUSION: Deletion of the
      Trpm4 gene in mice improved survival and significantly enhanced beta-adrenergic
      cardiac reserve after inducing ischaemic HF. This suggests that pharmacological
      or genetic down-regulation of TRPM4 function might be a novel strategy in the
      management of HF.

PMID- 25600963
TI  - Controlling ligand density on nanoparticles as a means to enhance biological
      activity.

PMID- 25600964
TI  - Highlights from the latest articles in nanoparticles, nanomaterials and
      nanotoxicity testing.

PMID- 25600962
TI  - Animal and in silico models for the study of sarcomeric cardiomyopathies.
AB  - Over the past decade, our understanding of cardiomyopathies has improved
      dramatically, due to improvements in screening and detection of gene defects in
      the human genome as well as a variety of novel animal models (mouse, zebrafish,
      and drosophila) and in silico computational models. These novel experimental
      tools have created a platform that is highly complementary to the naturally
      occurring cardiomyopathies in cats and dogs that had been available for some
      time. A fully integrative approach, which incorporates all these modalities, is
      likely required for significant steps forward in understanding the molecular
      underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies,
      including CRISPR/Cas9, which have already been proved to work in zebrafish, are
      currently being employed to engineer sarcomeric cardiomyopathy in larger animals,
      including pigs and non-human primates. In the mouse, the increased speed with
      which these techniques can be employed to engineer precise 'knock-in' models that
      previously took years to make via multiple rounds of homologous recombination
      based gene targeting promises multiple and precise models of human cardiac
      disease for future study. Such novel genetically engineered animal models
      recapitulating human sarcomeric protein defects will help bridging the gap to
      translate therapeutic targets from small animal and in silico models to the human
      patient with sarcomeric cardiomyopathy. 

PMID- 25600965
TI  - Computational modeling in nanomedicine: prediction of multiple antibacterial
      profiles of nanoparticles using a quantitative structure-activity relationship
      perturbation model.
AB  - AIMS: We introduce the first quantitative structure-activity relationship (QSAR)
      perturbation model for probing multiple antibacterial profiles of nanoparticles
      (NPs) under diverse experimental conditions. MATERIALS & METHODS: The dataset is
      based on 300 nanoparticles containing dissimilar chemical compositions, sizes,
      shapes and surface coatings. In general terms, the NPs were tested against
      different bacteria, by considering several measures of antibacterial activity and
      diverse assay times. The QSAR perturbation model was created from 69,231
      nanoparticle-nanoparticle (NP-NP) pairs, which were randomly generated using a
      recently reported perturbation theory approach. RESULTS: The model displayed an
      accuracy rate of approximately 98% for classifying NPs as active or inactive, and
      a new copper-silver nanoalloy was correctly predicted by this model with
      consensus accuracy of 77.73%. CONCLUSION: Our QSAR perturbation model can be used
      as an efficacious tool for the virtual screening of antibacterial nanomaterials.

PMID- 25600966
TI  - Enhanced biostability of nanoparticle-based drug delivery systems by albumin
      corona.
AB  - AIMS: The long-term efficacy of nanoparticles is limited by their rapid
      metabolism in tissues. In this work, we aim to enhance nanoparticle biostability
      by preforming a bovine serum albumin (BSA) corona. MATERIALS & METHODS: A BSA
      corona was formed by incubating poly-3-hydroxybutyrate-co-3-hydroxyhexanoate
      nanoparticles with BSA solution and confirmed by SDS-PAGE and x-ray photoelectron
      spectroscopy. The impacts of the BSA corona on the drug release, biostability and
      biodistribution of nanoparticles were investigated. RESULTS: In the presence of
      the BSA corona, the drug release (coumarin-6 was used as the model drug) of
      nanoparticles was significantly slower and their stability in liver homogenate
      and in organs was enhanced. CONCLUSION: Preformation of a BSA corona may be a
      promising approach for enhancing drug biostability and for developing long-acting
      nanoparticle formulations.

PMID- 25600967
TI  - Crucial role of the protein corona for the specific targeting of nanoparticles.
AB  - AIMS: We aimed to investigate the physicochemical effects of superparamagnetic
      iron oxide nanoparticles (SPIONs) on the composition of the protein corona and
      their correspondence toxicological issues. MATERIALS & METHODS: SPIONs of
      different sizes and surface charges were exposed to fetal bovine serum. The
      structure/composition and biological effects of the protein corona-SPION
      complexes were probed. RESULTS & DISCUSSION: The affinity and level of adsorption
      of specific proteins is strongly dependent on the size and surface charge of the
      SPIONs. In vivo experiments on the mouse blood-brain barrier model revealed that
      nontargeted SPIONs containing specific proteins will enter the brain endothelial
      barrier cells. CONCLUSION: Some commercially available nanoparticles used for
      target-specific applications may have unintended uptake in the body (e.g., brain
      tissue) with potential cytotoxity.

PMID- 25600968
TI  - Developing cutaneous applications of paromomycin entrapped in stimuli-sensitive
      block copolymer nanogel dispersions.
AB  - AIM: A new paromomycin micellar nanogel based on poloxamer 407 was developed.
      MATERIALS & METHODS:  In vitro release and ex vivo permeation/retention studies
      were conducted. In vivo tolerance was assayed by transepidermal water loss. Ex
      vivo cytotoxicity on RAW and VERO cells and antileishmanial activity on
      Leishmania promastigotes was tested. RESULTS: The particle size was 9.19 nm (99%
      loading efficiency) exhibiting Newtonian behavior at 4 degrees C and was
      pseudoplastic at 25 and 40 degrees C. Drug release followed a Weibull model and
      the drug remaining in the skin was 31.652 ug/g/cm(2). In vivo tolerance achieved
      excellent results with negligible cellular toxicity and the best antileishmanial
      efficiency. CONCLUSION: The nanogel provided controlled, effective and safe
      delivery of paromomycin for the treatment of cutaneous leishmaniasis.

PMID- 25600969
TI  - A strategy for combating melanoma with oncogenic c-Myc inhibitors and targeted
      nanotherapy.
AB  - AIMS: The activity of the transcription factor c-Myc is dependent upon
      heterodimerization with Max to control target gene transcription. Small-molecule
      inhibitors of c-Myc-Max have exhibited low potency and poor water solubility and
      are therefore unsuitable for in vivo application. We hypothesized that a
      nanomedicine approach incorporating a cryptic c-Myc inhibitor prodrug could be
      delivered and enzymatically released in order to effectively inhibit melanoma.
      MATERIALS & METHODS: An Sn-2 lipase-labile Myc inhibitor prodrug was synthesized
      and included in two alphavbeta3-targeted nanoparticle platforms (20 and 200 nm).
      The inherent antiproliferate potency was compared with the lipid-free compound
      using human and mouse melanoma cell lines. RESULTS & CONCLUSION: These data
      demonstrate for the first time a successful nanodelivery of c-Myc inhibitors and
      their potential use to prevent melanoma.

PMID- 25600970
TI  - Lipid nanoparticles for the topical delivery of retinoids and derivatives.
AB  - Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics
      for skin disorders. Conventional formulations are limited by poor water
      solubility, high chemical/photochemical instability and the irritation of
      retinoids. Interestingly, lipid nanoparticles enable the administration of
      retinoids in aqueous media, providing drug stabilization and controlled release.
      Recently, it has been demonstrated that retinoids in solid lipid nanoparticles,
      nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease
      degradation, improve targeting and enhance efficacy for the treatment of skin
      disorders. This article focuses on the formulation, fabrication, characterization
      and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured
      lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin
      administration. Furthermore, the incorporation of these lipid nanoparticles into
      secondary vehicles is discussed. 

PMID- 25600971
TI  - Micro/nano-structured superhydrophobic surfaces in the biomedical field: part II:
      applications overview.
AB  - The properties of surfaces define the acceptance and integration of biomaterials
      in vivo, as well as the material's efficiency when used at research or
      manufacturing levels. The presence of micro/nano-topographical structures and low
      surface energies could bring several advantages when highly repellent surfaces
      are employed in the biomedical field. Biomimetic superhydrophobic surfaces have
      been explored for diverse applications: as an intrinsic characteristic of
      biomaterials to be implanted; as materials that exhibit special interactions with
      biological entities; or to be used in ex vivo applications. This article aims to
      focus on the main motivations and requirements in the biomedical field that
      pushed for the utilization of superhydrophobic surfaces as suitable alternatives,
      as well as the great evolution of applications that have emerged in the last few
      years. 

PMID- 25600973
TI  - Gold nanoparticles as contrast agents in x-ray imaging and computed tomography.
AB  - Computed tomography enables 3D anatomic imaging at a high spatial resolution, but
      requires delivery of an x-ray contrast agent to distinguish tissues with similar
      or low x-ray attenuation. Gold nanoparticles (AuNPs) have gained recent attention
      as an x-ray contrast agent due to exhibiting a high x-ray attenuation,
      nontoxicity and facile synthesis and surface functionalization for colloidal
      stability and targeted delivery. Potential diagnostic applications include blood
      pool imaging, passive targeting and active targeting, where actively targeted
      AuNPs could enable molecular imaging by computed tomography. This article
      summarizes the current state of knowledge for AuNP x-ray contrast agents within a
      paradigm of key structure-property-function relationships in order to provide
      guidance for the design of AuNP contrast agents to meet the necessary functional
      requirements in a particular application. Functional requirements include
      delivery to the site of interest (e.g., blood, tumors or microcalcifications),
      nontoxicity during delivery and clearance, targeting or localization at the site
      of interest and contrast enhancement for the site of interest compared with
      surrounding tissues. Design is achieved by strategically controlling structural
      characteristics (composition, mass concentration, size, shape and surface
      functionalization) for optimized properties and functional performance. Examples
      from the literature are used to highlight current design trade-offs that exist
      between the different functional requirements. 

PMID- 25600975
TI  - De-mythifying breast reconstruction: a review of common misconceptions about
      breast reconstruction.

PMID- 25600972
TI  - Gold nanoparticles for photoacoustic imaging.
AB  - Photoacoustic (PA) imaging is a biomedical imaging modality that provides
      functional information regarding the cellular and molecular signatures of tissue
      by using endogenous and exogenous contrast agents. There has been tremendous
      effort devoted to the development of PA imaging agents, and gold nanoparticles as
      exogenous contrast agents have great potential for PA imaging due to their
      inherent and geometrically induced optical properties. The gold-based
      nanoparticles that are most commonly employed for PA imaging include spheres,
      rods, shells, prisms, cages, stars and vesicles. This article provides an
      overview of the current state of research in utilizing these gold nanomaterials
      for PA imaging of cancer, atherosclerotic plaques, brain function and image
      guided therapy. 

PMID- 25600974
TI  - A nationwide comparison of laparoscopic and open distal pancreatectomy for benign
      and malignant disease.
AB  - BACKGROUND: Cohort studies from expert centers suggest that laparoscopic distal
      pancreatectomy (LDP) is superior to open distal pancreatectomy (ODP) regarding
      postoperative morbidity and length of hospital stay. But the generalizability of
      these findings is unknown because nationwide data on LDP are lacking. STUDY
      DESIGN: Adults who had undergone distal pancreatectomy in 17 centers between 2005
      and 2013 were analyzed retrospectively. First, all LDPs were compared with all
      ODPs. Second, groups were matched using a propensity score. Third, the attitudes
      of pancreatic surgeons toward LDP were surveyed. The primary outcome was major
      complications (Clavien-Dindo grade >=III). RESULTS: Among 633 included patients,
      64 patients (10%) had undergone LDP and 569 patients (90%) had undergone ODP.
      Baseline characteristics were comparable, except for previous abdominal surgery
      and mean tumor size. In the full cohort, LDP was associated with fewer major
      complications (16% vs 29%; p = 0.02) and a shorter median [interquartile range,
      IQR] hospital stay (8 days [7-12 days] vs 10 days [8-14 days]; p = 0.03). Of all
      LDPs, 33% were converted to ODP. Matching succeeded for 63 LDP patients. After
      matching, the differences in major complications (9 patients [14%] vs 19 patients
      [30%]; p = 0.06) and median [IQR] length of hospital stay (8 days [7-12 days] vs
      10 days [8-14 days]; p = 0.48) were not statistically significant. The survey
      demonstrated that 85% of surgeons welcomed LDP training. CONCLUSIONS: Despite
      nationwide underuse and an impact of selection bias, outcomes of LDP seemed to be
      at least noninferior to ODP. Specific training is welcomed and could improve both
      the use and outcomes of LDP.

PMID- 25600976
TI  - Prevalence and Trends in Domestic Violence in South Korea: Findings From National
      Surveys.
AB  - To examine trends in the prevalence of domestic violence since 1997, 1 year prior
      to the introduction of legislative countermeasures and accompanying services in
      South Korea, and to analyze what socio-demographic characteristics of
      perpetrators contribute to spousal violence and whether there were any changes in
      risk factors over time. This study used two sets of nationally representative
      household samples: married or cohabiting couples of 1,540 from the 1999 national
      survey and 3,269 from the 2010 National Survey of Domestic Violence. Frequency
      analysis was used to measure the prevalence of intimate partner violence (IPV),
      and cross-tabulation, correlation, and logistic regression analyses were used to
      look for socio-demographic risk factors of spousal physical violence and patterns
      of change over time. The frequency analysis showed that the IPV prevalence
      dropped by approximately 50%, from 34.1% in 1999 to 16.5% in 2010, though it was
      still higher than many other countries. The cross-tabulation and logistic
      regression analyses suggested that men with low socio-demographic characteristics
      were generally more violent, though this tendency did not apply to women.
      Instead, younger women seemed to be more violent than older women. Last,
      different levels of household income were associated with different levels of IPV
      in 2010, but no linear trend was detected. In this study, IPV prevalence trends
      and risk factors of two different time periods were discussed to provide
      implications for tackling the IPV problem. Future countermeasures must build on
      understanding about men with low socio-demographic status and younger women, who
      were more violent in marital relationships. 

PMID- 25600977
TI  - A randomized, three-treatment, three-period, six-sequence-crossover, single
      center, bioequivalence study to evaluate the impact of different 10-mg
      crystalline forms on the pharmacokinetics of lenvatinib in healthy volunteers.
AB  - OBJECTIVE: This study assessed the impact of varying lenvatinib crystalline forms
      in 10-mg lenvatinib capsules on drug bioavailability in healthy volunteers.
      MATERIALS: Lenvatinib 10-mg capsules (low C and high C forms). METHODS: This
      randomized, three-period- crossover study compared the pharmacokinetics and
      safety of two crystalline forms of capsules (low C-form, <4% crystalline; high C
      form, 38% crystalline) to a standard (ref Cform, 15% crystalline). RESULTS: 59
      subjects were evaluable for pharmacokinetics. Test/reference ratios of the
      geometric least squares means (LSM) and 90% confidence intervals (CI) for AUC0-t
      (t up to 120 hours), AUC0-infinity, and Cmax for low C-form vs. ref C-form were
      101 (94.8, 107), 101 (95.3, 107), and 98.7 (88.6, 110), respectively; and for
      high C-form vs. ref C-form were 96.0 (92.1, 100), 96.5 (92.5, 101), and 90.6
      (83.5, 98.4), respectively. The incidence of treatment-emergent adverse events
      (TEAE) and treatment-related adverse events (TRAE) were comparable between all
      formulations (TEAE range 20-24%; TRAE range 15-19%). One serious TRAE
      (spontaneous abortion) occurred in the low C-form group. CONCLUSIONS: For both
      comparisons, the 90% CIs of the test/reference ratios were within the regulatory
      acceptance range (80-125%), suggesting that both test formulations (low Cform and
      high C-form) were bioequivalent to the reference formulation for Cmax, AUC0-t,
      and AUC0-infinity.

PMID- 25600978
TI  - Texture analysis of mandibular cortical bone on digital dental panoramic
      radiographs for the diagnosis of osteoporosis in Korean women.
AB  - OBJECTIVE: To determine whether individual measurements or a combination of
      textural features and mandibular cortical width (MCW) derived from digital dental
      panoramic radiographs (DPRs) are more useful in assessment of osteoporosis. STUDY
      DESIGN: Textural features were obtained by using fractal dimension (FD) and gray
      level co-occurrence matrix (GLCM). Digital DPRs and bone mineral densities (BMDs)
      of the lumbar spine and the femoral neck were obtained from 141 female patients.
      A naive Bayes classifier, a k-nearest neighbor (k-NN) algorithm, and a support
      vector machine were assessed for classifying osteoporosis. RESULTS: The
      combinations of FD plus MCW (95.3%, 92.1%, 96.8%) and GLCM plus MCW (93.7%,
      89.5%, 94.2%) for femoral neck BMD showed the highest diagnostic accuracy with
      the use of the naive Bayes, k-NN, and support vector machine classifiers,
      respectively. CONCLUSIONS: The combination of textural features and MCW
      contributed a better assessment of osteoporosis compared with the use of only
      individual measurements.

PMID- 25600979
TI  - Twenty-first-century oral hairy leukoplakia--a non-HIV-associated entity.
AB  - OBJECTIVE: This study presents the clinicopathologic features of a series (N =
      35) of patients with non-human immunodeficiency virus (HIV)-associated oral hairy
      leukoplakia (OHL). METHODS: Patients with non-HIV-associated OHL were identified
      from three centers. Epstein-Barr virus infection was demonstrated by using EBV
      early ribonucleic acid in situ hybridization. The presence of Candida co
      infection was evaluated by diastase periodic acid-Schiff staining. The clinical
      features were determined by review of the medical records. RESULTS: Twenty-eight
      patients had intercurrent respiratory problems requiring long-term steroid
      inhaler use, four suffered from autoimmune diseases requiring immunosuppressant
      therapy, and four had diabetes. The majority of lesions were located on the
      tongue, and 24 showed evidence of Candida co-infection. CONCLUSIONS: In the
      twenty-first century, the presence of OHL should not be regarded as pathognomic
      for HIV infection or significant systemic immunosuppression. Local and systemic
      immunosuppression, in the form of steroid inhaler use, is a risk factor for the
      development of OHL.

PMID- 25600980
TI  - Comparison of the prevalence of human papilloma virus infection in
      histopathologically confirmed premalignant oral lesions and healthy oral mucosa
      by brush smear detection.
AB  - OBJECTIVE: The role of human papilloma virus (HPV) infections in oral
      carcinogenesis is an important topic of research in maxillofacial oncology.
      Nevertheless, the association between such infections in the oral cavity and the
      development of oral precancerous lesions remains unclear. The aim of this study
      was to evaluate the association between oral HPV infections and oral leukoplakia
      or erythroplakia. STUDY DESIGN: The case control study included 118 patients with
      manifest oral leukoplakia or erythroplakia, who underwent surgical biopsy,
      including a histopathologic grading of the lesion, and 100 control patients
      without any oral lesions. HPV detection was achieved with a noninvasive brush
      smear method (Digene Cervical Sampler, Hybrid Capture II-Test). Logistic
      regression analysis was performed to assess the associations. RESULTS: A
      significant association was found between high-risk oral HPV infection and the
      presence of oral premalignant lesions (P = .001). Among all other evaluated
      parameters, only smoking showed a significant association with the presence of
      oral lesions. CONCLUSIONS: Oral HPV infections may play a role in the
      pathogenesis of premalignant oral lesions.

PMID- 25600981
TI  - Gemcitabine interacts with carbonate apatite with concomitant reduction in
      particle diameter and enhancement of cytotoxicity in breast cancer cells.
AB  - Substantial amount of research has been done in recent decades for the
      development of nanoparticle systems to selectively deliver drugs to cancer cells
      for concurrently enhancing and reducing anti-cancer and off-target effects,
      respectively. pH-sensitive carbonate apatite (CA) was originally developed for
      efficient and targeted delivery of DNA, siRNA and proteins to various cancer cell
      lines. Recently, the CA particles were employed to deliver anti-cancer drugs,
      cyclophosphamide, doxorubicin and methotrexate to cancer cells. Here, we report
      on the fabrication and characterization of gemcitabine- loaded CA particles,
      followed by the evaluation of their roles in enhancement of cytotoxicity in two
      human and one murine breast cancer cell lines. HPLC was performed to measure
      binding efficiency of the drug to the apatite particles whereas particle size and
      zeta potential were evaluated to characterize drug/apatite complex. Depending on
      the initial doses of the drug, its bind binding affinity towards the particles
      varied from 3.85% to 4.45%. The particle size was found to surprisingly decrease
      with an increase of the initial drug concentration. In vitro chemosensitivity
      assay revealed that apatite/drug nanoparticle complexes presented significantly
      higher cytotoxicity to breast cancer cells compared to free drugs, which could be
      correlated with the enhanced cellular uptake of the small size drug-loaded
      particles through endocytosis compared to the passive diffusion of the free drug.

PMID- 25600982
TI  - Development and Pharmacokinetic Evaluation of Industrially Viable Self
      microemulsifying Drug Delivery Systems (SMEDDS) for Terbinafine.
AB  - Objective: The aim of this study was to develop a formulation for lymphatic
      uptake with enhanced solubility of antifungal drug, terbinafine by use of self
      microemulsifying drug delivery system (SMEDDS); suitable enough to be an
      industrially feasible and acceptable dosage form. Methods: Fabrication of pseudo
      ternary phase diagram was done with suitable oils, surfactants and co
      surfactants. The optimized formulation was characterised for droplet size,
      polydispersity index, zeta potential, cross-polarized light microscopy,
      thermodynamic stability, viscosity, capsule compatibility and evaluated for in
      vitro- in vivo parameters. The formulation was tested in animal model for
      lymphatic uptake with and without chylomicron blocking agent followed by the
      pharmacokinetic evaluation of the same. Results: The self-emulsification time,
      droplet size, polydispersity index of the optimized formulation remained
      unaffected in different media (water, 0.1N HCl and phosphate buffer pH 6.8) over
      stability conditions and with time. Crossed-polarized light microscopy
      examination of diluted SMEDDS formulation indicated that the dispersion was an
      isotropically stable system. The rate of dissolution for SMEDDS formulation was
      almost double as compared to marketed formulation (Lamisil(r)). Current
      investigation indicated a potential for lymphatic uptake of lipid based SMEDDS
      formulation with enhanced solubility of the candidate drug terbinafine. The
      optimum formulation of terbinafine SMEDDS when orally administered to rat with
      and without chylomicron flow blocking agent (cycloheximide) showed the area under
      the curve (AUC0-48hrs) as 10168.17 ng h/ml and 7425.44 ng h/ml respectively
      indicating the absorption through the lymphatic route. Thus, the study shows use
      of SMEDDS formulation for the drug delivery by lymphatic uptake.

PMID- 25600983
TI  - Clinical trials of helminth therapy in autoimmune diseases: rationale and
      findings.
AB  - Some helminths are major human pathogens. Recently, however, increased
      understanding of the immunoregulatory responses induced by this class of
      parasites, in combination with epidemiologic and animal studies, suggests that
      helminths may have therapeutic potential in autoimmune diseases (AD) and other
      conditions. This article reviews the rationale for and results of clinical trials
      to test the safety and efficacy of helminth therapy in AD. Also discussed are
      future prospects for investigation and the possibility that helminth treatment
      may serve as a probe to help reveal the pathogenesis of AD. 

PMID- 25600984
TI  - Sulfur and selenium antioxidants: challenging radical scavenging mechanisms and
      developing structure-activity relationships based on metal binding.
AB  - Because sulfur and selenium antioxidants can prevent oxidative damage, numerous
      animal and clinical trials have investigated the ability of these compounds to
      prevent the oxidative stress that is an underlying cause of cardiovascular
      disease, Alzheimer's disease, and cancer, among others. One of the most common
      sources of oxidative damage is metal-generated hydroxyl radical; however, very
      little research has focused on determining the metal-binding abilities and
      structural attributes that affect oxidative damage prevention by sulfur and
      selenium compounds. In this review, we describe our ongoing investigations into
      sulfur and selenium antioxidant prevention of iron- and copper-mediated oxidative
      DNA damage. We determined that many sulfur and selenium compounds inhibit Cu(I)
      mediated DNA damage and that DNA damage prevention varies dramatically when
      Fe(II) is used in place of Cu(I) to generate hydroxyl radical. Oxidation
      potentials of the sulfur or selenium compounds do not correlate with their
      ability to prevent DNA damage, highlighting the importance of metal coordination
      rather than reactive oxygen species scavenging as an antioxidant mechanism.
      Additional gel electrophoresis, mass spectrometry, and UV-visible studies
      confirmed sulfur and selenium antioxidant binding to Cu(I) and Fe(II).
      Ultimately, our studies established that both the hydroxyl-radical-generating
      metal ion and the chemical environment of the sulfur or selenium significantly
      affect DNA damage prevention and that metal coordination is an essential
      mechanism for these antioxidants. 

PMID- 25600985
TI  - In vitro antioxidant and antidiabetic activities of biomodified lignin from
      Acacia nilotica wood.
AB  - The antioxidant and antidiabetic activity of biomodified alkali lignin extracted
      from a deciduous plant Acacia nilotica, was evaluated in vitro. The extracted
      alkali lignin was subjected to microbial biotransformation by ligninolytic fungus
      Aspergillus flavus and Emericella nidulans. These modifications were done under
      varying concentration of carbon to nitrogen sources. The structural feature of
      the lignin samples were compared by FTIR, functional group analysis and (13)C
      solid state NMR. All lignin samples were tested for antioxidant efficiency,
      reducing power and H2O2 scavenging power. Modifications in all lignin samples
      showed correlation with their antioxidant scavenging activity and reducing power.
      Antidiabetic properties were evaluated in terms of in vitro glucose movement
      inhibition and alpha-amylase inhibition assay. Modified samples exhibited
      increased glucose binding efficiency as demonstrated by the decreased glucose
      diffusion (55.5-76.3%) and 1.16-1.18-fold enhanced alpha-amylase inhibition in
      comparison to their control samples. The results obtained demonstrate that the
      structure and functional modifications in lignin significantly affects its
      bioefficacy in term of antioxidant and antidiabetic activities. 

PMID- 25600986
TI  - Extracted polysaccharide from Nyctanthes arbor-tristis leaves: chemical and
      antitussive properties.
AB  - The prevalence of cough is reflected in antitussives being one of the most widely
      used therapies in the world; however no new class of drugs has been introduced
      into the market for many years. Water decoction of the leaves of Nyctanthes arbor
      tristis L. is used in Indian Ayurvedic system to alleviate a wide range of
      diseases including cough. Herein, we have isolated a carbohydrate polymer (CP)
      containing fraction from its leaves by aqueous extraction method. CP is a
      branched polysaccharide containing, amongst others, 1,3-/1,3,6-linked
      galactopyranosyl, 1,5-/1,3,5-linked arabinofuranosyl and 1,2-/1,2,4-linked
      rhamnopyranosyl residues. Oral administration of CP fraction in doses of 25 and
      50 mg kg(-1) body weight significantly inhibited the number of citric acid
      induced cough efforts in guinea pigs in a dose dependent manner. Remarkably, CP
      did not altered specific airway resistance of animals significantly.
      Consequently, aqueous extraction method provided a molecular entity, which
      exhibited the cough suppressive activity: this could symbolize an attractive
      approach in phytotherapeutic treatment.

PMID- 25600987
TI  - Mitochondrial membrane disruption by aggregation products of ALS-causing
      superoxide dismutase-1 mutants.
AB  - More than 140 mutations in the SOD1 gene cause aggregation of the affected
      protein in familial forms of amyotrophic lateral sclerosis (fALS) which is a
      fatal progressive neurodegenerative disorder selectively affecting motor neurons.
      The causes of motor neuron death in ALS are poorly understood in general, but for
      fALS, aberrant oligomerization of SOD1 mutant proteins has been strongly
      concerned. Increasing evidences indicate that the interaction of amyloid
      aggregates with membranes is critical in the onset and progression of amyloid
      diseases. In spite of gathering reports describing mechanisms of membrane
      permeabilization by aggregates in model membranes, studies focused at
      characterizing the events occurring in biological membranes are exceptional. To
      gain insight into possible mechanisms of cytotoxicity at the membrane level, we
      describe interaction of the fibrillation products of the wild type (WT) and two
      mutants (E100K, D125H) of SOD1 obtained under destabilizing conditions with
      mitochondrial membranes. Release of mitochondrial enzymes, malate dehydrogenase
      (MDH) and adenylate kinase (AK), upon exposure to SOD1 aggregates demonstrates
      that these aggregates could affect membrane integrity. This effect correlates
      with the surface hydrophobicity of oligomers and their tendency toward amyloid
      formation, with the most toxic oligomers having high hydrophobicity and increased
      amount of amyloid formation. 

PMID- 25600988
TI  - Enhancement of thermal reversibility and stability of human carbonic anhydrase II
      by mesoporous nanoparticles.
AB  - Aminopropyl functionalized PEGylated mesoporous silica nanoparticles [H2N
      Pr@PEGylated SBA-15] were synthesized and evaluated as a promising biocompatible
      additive to study the activity and thermal reversibility and stability of human
      carbonic anhydrase II (HCA II). For this purpose, the additive was prepared by
      covalent amino propyl functionalization of mesoporous silica nanoparticles (MSNs)
      bearing PEG moiety as linker. The MSNs was fully characterized using different
      techniques including transmission electron microscopy, N2 adsorption-desorption
      measurements, thermal gravimetric analysis, Fourier transform infrared
      spectroscopy and dynamic light scattering. The average particle size of [H2N
      Pr@PEGylated SBA-15] was about 80 nm and showed high loading capacity for HCA II
      at pH 7.75 as a target protein. The efficiency of [H2N-Pr@PEGylated SBA-15] in
      improving reversibility of HCA II was investigated by various techniques
      including UV-vis, 1,8-Anilinonaphtalene Sulfonate (ANS) fluorescence, circular
      dichroism (CD), and differential scanning calorimetry. Our results showed that
      [H2N-Pr@PEGylated SBA-15] can increase the protein thermal reversibility and
      stability. Herein, kinetic studies were applied to confirm the ability of [H2N
      Pr@PEGylated SBA-15] in increasing the activity of HCA II at high temperatures.
      Together our results present the [H2N-Pr@PEGylated SBA-15] as a water-dispersible
      and efficient additive for improving the activity, and thermal reversibility and
      stability of enzyme.

PMID- 25600989
TI  - Exopolysaccharide produced by Pleurotus sajor-caju: its chemical structure and
      anti-inflammatory activity.
AB  - Edible mushrooms are high nutritional value foods, which contain proteins,
      fibers, minerals, vitamins, and carbohydrates. Among their carbohydrates are some
      polysaccharides with recognized therapeutic effects. It was reported in this
      manuscript the structural characterization and antinociceptive and anti
      inflammatory activities of an exopolysaccharide (EPS) produced by Pleurotus sajor
      caju. The purified EPS was a mannogalactan (PEIsR), which was composed by mannose
      (37.0%), galactose (39.7%), and 3-O-methyl-galactose (23.3%). The polysaccharide
      was purified by freeze-thawing and dialysis, and it was characterized by GC-MS
      analysis and NMR spectroscopy. The mannogalactan is constituted by a main chain
      of (1 -> 6)-linked alpha-D-Galp and 3-O-methyl-alpha-D-Galp units. Some of the
      alpha-D-Galp units were substituted at O-2 by non-reducing end units of beta-D
      Manp. According to the literature review conducted, this is the first time that a
      methylated polysaccharide was observed on EPS of P. sajor-caju. The mannogalactan
      was able to reduce the nociception, in vivo, in the writhing and formalin tests
      and also reduced the carrageenan-induced paw edema, which indicates that it could
      be an effective antinociceptive and anti-inflammatory agent.

PMID- 25600990
TI  - Long-term results of the use of oxybutynin for the treatment of plantar
      hyperhidrosis.
AB  - BACKGROUND: Plantar hyperhidrosis is a common illness with significant impact on
      quality of life. Oxybutynin presents good short-term results, but longer follow
      up results are lacking. We evaluated oxybutynin effectiveness in patients who
      were not surgically treated and who had at least six months of follow-up.
      METHODS: From September 2007 to September 2013, 85 consecutive patients were
      enrolled in our institutional protocol for the "pharmacological-first" treatment
      of primary plantar hyperhidrosis with oxybutynin. Eight patients were lost to
      follow-up, 15 patients have not yet been under treatment for six months, and data
      were available for 39 patients (all female) treated for at least six months. Data
      at the start of the protocol, six weeks after beginning treatment, and at their
      final visit were analyzed. RESULTS: Twenty-three of the 77 patients (29.87%) did
      not improve after pharmacological therapy. From the 39 patients with more than
      six months of follow-up (median 16.9 months, range 9-71), 79.5% reported
      moderate/great improvement in excessive plantar sweating after six weeks of
      treatment, and this rate increased to 84.7% in the last follow-up visit; 82.85%
      showed improvement in other sites presenting hyperhidrosis. Dry mouth was the
      most common side effect; 51.6% of patients reported it to be moderate/severe at
      the last visit. CONCLUSION: In patients with good initial response to oxybutynin,
      more than 82% presented moderate or great improvement in plantar and other sites'
      excessive sweating; dry mouth was the most common side effect but was tolerable
      and did not lead any patient to interrupt treatment.

PMID- 25600991
TI  - Trapping and assembly of living colloids at water-water interfaces.
AB  - We study the assembly of inert and living colloids in a two-phase water-water
      system that provides an environment that can sustain bacteria, providing a new
      structure with rich potential to confine and structure microbial communities. The
      water-water system, formed via phase separation of a casein and xanthan mixture,
      forms a 3-D structure of coexisting casein-rich and xanthan-rich phases.
      Fluorescent labelling and confocal microscopy reveal the attachment of these
      living colloids, including Escherichia coli and Pseudomonas aeruginosa, at the
      interface between the two phases. Inert colloids also become trapped at the
      interfaces, suggesting that the observed attachment can be attributed to
      capillarity. Over time, these structures coarsen and eventually degrade,
      illustrating the dynamic nature of these systems. This system lays the foundation
      for future studies of the interplay of physicochemical properties of the fluid
      interfaces and bulk phases and microbial responses they provoke to induce complex
      spatial organization, to study species which occupy distinct niches, and to
      optimize efficient microbial cross-feeding or protection from competitors. 

PMID- 25600992
TI  - Volatile constituents of Amomum maximum Roxb and Amomum microcarpum C. F. Liang &
      D. Fang: two Zingiberaceae grown in Vietnam.
AB  - The chemical composition of essential oils obtained from the hydrodistillation of
      different parts of Amomum maximum Roxb and Amomum muricarpum C. F. Liang & D.
      Fang (Zingiberaceae) grown in Vietnam are reported. The analysis was performed by
      means of gas chromatography-flame ionisation detectoorand gas chromatography
      coupled with mass spectrometry. The major compounds identified in the oils of A.
      maximum were beta-pinene (20.4-40.8%), alpha-pinene (6.8-15.0%), beta-elemene
      (2.5-12.8%) and beta-caryophyllene (2.3-10.3%). Moreover, beta-phellandrene
      (11.6%) was present in the root oil. The main compound identified in all the oil
      samples of A. muricarpum was alpha-pinene (24.1-54.7%) and beta-pinene (9.2
      25.9%). In addition, limonene (7.4%) and delta-3-carene (9.4%) were present in
      the leaves and stem oils, respectively. However, while beta-phellandrene (8.3%)
      could be seen prominent in the root oil, the fruits contained significant amount
      of zingiberene (6.3%). The largest amount of tau-muurolol (13.0%) was found in
      the flower oil.

PMID- 25600993
TI  - Catalytic activity of acid and base with different concentration on sol-gel
      kinetics of silica by ultrasonic method.
AB  - The effects of both acid (acetic acid) and base (ammonia) catalysts in varying on
      the sol-gel synthesis of SiO2 nanoparticles using tetra ethyl ortho silicate
      (TEOS) as a precursor was determined by ultrasonic method. The ultrasonic
      velocity was received by pulsar receiver. The ultrasonic velocity in the sol and
      the parameter DeltaT (time difference between the original pulse and first back
      wall echo of the sol) was varied with time of gelation. The graphs of
      ln[ln1/DeltaT] vs ln(t), indicate two region - nonlinear region and a linear
      region. The time corresponds to the point at which the non-linear region change
      to linear region is considered as gel time for the respective solutions. Gelation
      time is found to be dependent on the concentration and types of catalyst and is
      found from the graphs based on Avrami equation. The rate of condensation is found
      to be faster for base catalyst. The gelation process was also characterized by
      viscosity measurement. Normal sol-gel process was also carried out along with the
      ultrasonic one to compare the effectiveness of ultrasonic. The silica gel was
      calcined and the powdered sample was characterized with scanning electron
      microscopy, energy dispersive spectra, X-ray diffractogram, and FTIR
      spectroscopy. 

PMID- 25600994
TI  - Interaction of collagen like peptides with gold nanosurfaces: a molecular
      dynamics investigation.
AB  - In this study, an attempt has been made to understand the interaction between
      collagen like peptides (CPs) with a gold nanosurface (AuNS) using a classical
      molecular dynamics simulation. Results reveal that the adsorption of CPs onto the
      gold surface depends on the amino acid composition of the collagen like peptides.
      It is evident from the findings that the Hyp residue of collagen interacts
      favorably with the AuNS. It is interesting to note that the model CP without a
      Hyp residue does not adsorb well on the surface. Results indicate that gold
      nanosurfaces or gold nanoparticles can be exploited to detect breast cancer due
      to the increased content of Hyp residues in the Gly-XAA-YAA triplet of collagen
      in breast cancer tissues. These results provide useful information for designing
      collagen based scaffolds for tissues engineering applications. 

PMID- 25600995
TI  - Improvement of dizocilpine-induced social recognition deficits in mice by
      brexpiprazole, a novel serotonin-dopamine activity modulator.
AB  - Cognitive impairment, including impaired social cognition, is largely responsible
      for the deterioration in social life suffered by patients with psychiatric
      disorders, such as schizophrenia and major depressive disorder (MDD).
      Brexpiprazole (7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)
      one), a novel serotonin-dopamine activity modulator, was developed to offer
      efficacious and tolerable therapy for different psychiatric disorders, including
      schizophrenia and adjunctive treatment of MDD. In this study, we investigated
      whether brexpiprazole could improve social recognition deficits (one of social
      cognition deficits) in mice, after administration of the N-methyl-d-aspartate
      (NMDA) receptor antagonist MK-801 (dizocilpine). Dosing with dizocilpine
      (0.1mg/kg) induced significant impairment of social recognition in mice.
      Brexpiprazole (0.01, 0.03, 0.1mg/kg, p.o.) significantly ameliorated dizocilpine
      induced social recognition deficits, without sedation or a reduction of
      exploratory behavior. In addition, brexpiprazole alone had no effect on social
      recognition in untreated control mice. By contrast, neither risperidone
      (0.03mg/kg, p.o.) nor olanzapine (0.03mg/kg, p.o.) altered dizocilpine-induced
      social recognition deficits. Finally, the effect of brexpiprazole on dizocilpine
      induced social recognition deficits was antagonized by WAY-100,635, a selective
      serotonin 5-HT1A antagonist. These results suggest that brexpiprazole could
      improve dizocilpine-induced social recognition deficits via 5-HT1A receptor
      activation in mice. Therefore, brexpiprazole may confer a beneficial effect on
      social cognition deficits in patients with psychiatric disorders.

PMID- 25600996
TI  - Response to Dallosso et al. Self-monitoring of blood glucose versus self
      monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes
      receiving structured education: a cluster randomized controlled trial.

PMID- 25600998
TI  - Sulfate influx transporters in Arabidopsis thaliana are not involved in arsenate
      uptake but critical for tissue nutrient status and arsenate tolerance.
AB  - MAIN CONCLUSION: Arsenic, a non-nutrient metalloid is toxic to plants but many
      details on the physiology of plant adaptation to arsenic stress are not well
      understood. This work provides new insights about the role of sulfur assimilation
      in arsenate uptake, growth and arsenic tolerance. Research reported here
      indicates that two high affinity sulfate transporters in Arabidopsis thaliana are
      not involved in root uptake of arsenate. Further this study revealed that sulfate
      status influenced thiol levels, elemental nutrients, growth and arsenate
      tolerance. The hypothesis that arsenate may be transported via sulfate
      transporters, SULTR1;1 and SULTR1;2 in Arabidopsis, was tested. The double mutant
      of sultr1;1 sultr1;2 exhibited significantly less growth than the wild-type or
      the single mutants. The double mutant's sulfur content was significantly lower
      than the wild-type but the single mutants were similar to the wild-type
      confirming the redundant functions of SULTR1;1 and SULTR1;2. Gene expression
      analyses indicated that the double mutant's sulfate uptake could be explained by
      the expressions of SULTR1;3, SULTR2;1, and SULTR2;2 in its roots. Following
      arsenate supply to the roots, the double mutant accumulated significantly less
      arsenic in the roots and the shoots than did the single mutants and the wild
      type. The double mutant accumulated significantly less potassium and phosphorus
      also. (35)S sulfate supplied to wild-type or double mutant roots showed that
      sulfate uptake was not inhibited by arsenate. Taken together, these results
      indicate that root uptake of arsenate is probably not via sulfate transporters,
      but the poor growth of the double mutant of sultr1;1 and sultr1;2 was due to its
      poor sulfate status and decreased levels of thiols, which had pleiotropic effects
      on the root uptake and translocation of potassium and phosphorus and arsenic
      tolerance.

PMID- 25600997
TI  - Linked circadian outputs control elongation growth and flowering in response to
      photoperiod and temperature.
AB  - Clock-regulated pathways coordinate the response of many developmental processes
      to changes in photoperiod and temperature. We model two of the best-understood
      clock output pathways in Arabidopsis, which control key regulators of flowering
      and elongation growth. In flowering, the model predicted regulatory links from
      the clock to cycling DOF factor 1 (CDF1) and flavin-binding, KELCH repeat, F-box
      1 (FKF1) transcription. Physical interaction data support these links, which
      create threefold feed-forward motifs from two clock components to the floral
      regulator FT. In hypocotyl growth, the model described clock-regulated
      transcription of phytochrome-interacting factor 4 and 5 (PIF4, PIF5), interacting
      with post-translational regulation of PIF proteins by phytochrome B (phyB) and
      other light-activated pathways. The model predicted bimodal and end-of-day PIF
      activity profiles that are observed across hundreds of PIF-regulated target
      genes. In the response to temperature, warmth-enhanced PIF4 activity explained
      the observed hypocotyl growth dynamics but additional, temperature-dependent
      regulators were implicated in the flowering response. Integrating these two
      pathways with the clock model highlights the molecular mechanisms that coordinate
      plant development across changing conditions.

PMID- 25600999
TI  - Rice RING E3 ligase may negatively regulate gamma-ray response to mediate the
      degradation of photosynthesis-related proteins.
AB  - MAIN CONCLUSION: In this study, our findings regarding the regulation of GA
      irradiation-induced OsGIRP1 in relation to the levels of photosynthesis-related
      proteins such as OsrbcL1 and OsrbcS1 and hypersensitive responses of
      overexpressing plants to GR irradiation provide insight into the molecular
      functions of OsGIRP1 as a negative regulator in response to the stress of
      radiation. The RING (Really Interesting New Gene) finger proteins are known to
      play crucial roles in various abiotic stresses in plants. Here, we report on RING
      finger E3 ligase, Oryza sativa gamma rays-induced RING finger protein1 gene
      (OsGIRP1), which is highly induced by gamma rays (GR) irradiation. In vitro
      ubiquitination assay demonstrated that a single amino acid substitution
      (OsGIRP1(C196A)) of the RING domain showed no E3 ligase activity, supporting the
      notion that the activity of most E3s is specified by a RING domain. We isolated
      at least 6 substrate proteins of OsGIRP1, including 2 Rubisco subunits, OsrbcL1
      and OsrbcSl, via yeast two-hybridization and bimolecular fluorescence
      complementation assays. OsGIRP1 and its partner proteins were targeted to the
      cytosol and the cytosol or chloroplasts, respectively; however, florescence
      signals of the complexes with OsGIPR1 were observed in the cytosol. Protein
      degradation in cell extracts showed that OsGIRP1 mediates proteolysis of 2
      substrates, OsrbcS1 and OsrbcL1, via the 26S proteasome degradation pathway. The
      Arabidopsis plants overexpressing OsGIRP1 clearly exhibited increased sensitivity
      to GR irradiation. These results might suggest that OsGIRP1 acts as a negative
      regulator of GR response to mediate the degradation of photosynthesis-related
      proteins.

PMID- 25601000
TI  - Identification and characterization of mRNA-like noncoding RNAs in Salvia
      miltiorrhiza.
AB  - MAIN CONCLUSION: Identification and characterization of 5,446 mlncRNAs from
      Salvia miltiorrhiza showed that the majority of identified mlncRNAs were stress
      responsive, providing a framework for elucidating mlncRNA functions in S.
      miltiorrhiza. mRNA-like noncoding RNAs (mlncRNAs) are transcribed by RNA
      polymerase II and are polyadenylated, capped and spliced. They play important
      roles in plant development and defense responses. However, there is no
      information available for mlncRNAs in Salvia miltiorrhiza Bunge, the first
      Chinese medicinal material entering the international market. To perform a
      transcriptome-wide identification of S. miltiorrhiza mlncRNAs, we assembled over
      8 million RNA-seq reads from GenBank database and 5,624 ESTs from PlantGDB into
      44422 unigenes. Using a computational identification pipeline, we identified 5446
      S. miltiorrhiza mlncRNA candidates from the assembled unigenes. Of the 5446
      mlncRNAs, 2 are primary transcripts of conserved miRNAs, and 2030 can be grouped
      into 470 families with at least two members in a family. Quantitative real-time
      PCR analysis of mlncRNAs with at least 900 nt showed that the majority were
      differentially expressed in roots, stems, leaves and flowers and responsive to
      methyl jasmonate (MeJA) treatment in S. miltiorrhiza. Analysis of published RNA
      seq data showed that a total of 3,044 mlncRNAs were expressed in hairy roots of
      S. miltiorrhiza and the expression of 1,904 of the 3,044 mlncRNAs was altered by
      yeast extract and Ag(+) treatment. The results indicate that the majority of
      mlncRNAs are involved in plant response to stress. This study provides a
      framework for understanding the roles of mlncRNAs in S. miltiorrhiza.

PMID- 25601002
TI  - Ultrastructural analysis of five patients with total sperm immotility.
AB  - Asthenozoospermia has been related to structural defects of the sperm flagellum.
      However, few reports have studied in detail the ultrastructure of sperm with
      total immotility. We present an ultrastructural study of sperm from five patients
      with total sperm immotility, four due to dysplasia of the fibrous sheath (DFS)
      and one with situs-inversus. Of the four patients with DFS, three cases presented
      a hypertrophic and hyperplastic fibrous sheath that invaded the midpiece space,
      absence of the annulus, and a short midpiece containing a few disorganized and
      pale mitochondria. Of these cases, two presented absence of the central complex
      and radial spokes; another additionally presented absence of dynein arms and
      nexin bridges; and the other patient presented an intact annulus with a
      dysplastic fibrous sheath restricted to the principal piece with disorganized
      microtubule doublets. The patient with situs-inversus presented severe
      respiratory symptoms, with absence of dynein arms and nexin bridges. In
      conclusion, we present three cases with DFS associated with total sperm
      immotility, abnormal mitochondria, and absence of the annulus, central pair
      complex and radial spokes, of which one had in addition absence of dynein arms
      and nexin bridges. We also describe a patient, with total sperm immotility and a
      different presentation of DFS, as the annulus was present and the dysplastic
      fibrous sheath was restricted to the principal piece. These findings thus confirm
      the heterogeneity of the DFS condition. The changes observed in the patient with
      situs-inversus also further support previous observations. 

PMID- 25601001
TI  - When is birthweight at term (>=37 weeks' gestation) abnormally low? A systematic
      review and meta-analysis of the prognostic and predictive ability of current
      birthweight standards for childhood and adult outcomes.
AB  - BACKGROUND: Health outcomes throughout the life course have been linked to fetal
      growth restriction and low birthweight. A variety of measures exist to define low
      birthweight, with a lack of consensus regarding which predict adverse outcome.
      OBJECTIVES: To evaluate the relationship between birthweight standards and
      childhood and adult outcomes in term-born infants (>=37 weeks' gestation). SEARCH
      STRATEGY: MEDLINE (1966-January 2011), EMBASE (1980-January 2011), and the
      Cochrane Library (2011:1) and MEDION were included. SELECTION CRITERIA: Studies
      comprising live term-born infants (gestation >=37 completed weeks), with weight
      or other anthropometric measurements recorded at birth along with childhood and
      adult outcomes. DATA COLLECTION AND ANALYSIS: Data were extracted to populate 2 *
      2 tables relating birthweight standard with outcome, and meta-analysis was
      performed where possible. MAIN RESULTS: Fifty-nine articles (2 600 383
      individuals) were selected. There was no significant relationship between
      birthweight <2.5 kg (odds ratio [OR] 0.98, 95% confidence intervals [CI] 0.87
      1.10) and composite measure of childhood morbidity. Weight <10th centile on the
      population nomogram showed a small association (OR 1.49, 95% CI 1.02-2.19) for
      the same outcome. There was no significant association between either of the
      above measures and adult morbidity. The relationship between other measures and
      individual outcomes varied. AUTHOR'S CONCLUSIONS: The association between low
      birthweight, by any definition, and childhood and adult morbidity was
      inconsistent. None of the current standards of low birthweight was a good
      predictor of adverse outcome.

PMID- 25601004
TI  - Reputation can enhance or suppress cooperation through positive feedback.
AB  - One possible explanation for the widespread existence of cooperation in nature is
      that individuals cooperate to establish reputations and so benefit in future
      interactions with others. We consider a class of games in which individuals
      contribute to a common good at a cost to themselves. Population members vary in
      type, that is, in the cost paid for a given level of contribution. We consider a
      form of indirect reciprocity in which the contribution of an individual depends
      on their partner's reputation and their own type. Here we show that for such
      games, reputation destabilizes the selfish equilibrium through a novel and robust
      feedback mechanism. For those games in which the selfish optimal contribution to
      the common good increases as the contribution of the partner increases, the
      feedback mechanism enhances cooperation levels. In contrast, when the optimal
      contribution decreases as partner's contribution increases, cooperation levels
      are reduced still further. 

PMID- 25601005
TI  - Configural and featural face processing are differently modulated by attentional
      resources at early stages: an event-related potential study with rapid serial
      visual presentation.
AB  - It is widely reported that face recognition relies on two dissociable mechanisms,
      the featural and the configural processing. However, it is unclear whether these
      two processing types involve different neural mechanisms and are differently
      modulated by attentional resources. Using the attentional blink (AB) paradigm, we
      aimed to investigate the effect of attentional resources on configural and
      featural face processing by recording event-related potentials (ERPs). The amount
      of attentional resources was manipulated as deficient or sufficient by presenting
      the second target (T2) in or out of the AB period, respectively. We found that in
      addition to a traditional P3 attention effect, the amplitude of N170/VPP to the
      T2 stimuli was also sensitive to attentional resources, suggesting that attention
      affects face processing at an earlier perceptual processing stage. More
      importantly, configural face processing elicited a larger posterior P1 compared
      to featural face processing, but only when the attentional resources were
      sufficient. In contrast, the anterior N1 was larger for configural relative to
      featural face processing only when the attentional resources were deficient.
      These results suggest that early stages of configural and featural face
      processing are differently modulated by attentional resources, possibly with
      different underlying mechanisms. 

PMID- 25601003
TI  - The relationship between gamma frequency and running speed differs for slow and
      fast gamma rhythms in freely behaving rats.
AB  - In hippocampal area CA1 of rats, the frequency of gamma activity has been shown
      to increase with running speed (Ahmed and Mehta, 2012). This finding suggests
      that different gamma frequencies simply allow for different timings of
      transitions across cell assemblies at varying running speeds, rather than serving
      unique functions. However, accumulating evidence supports the conclusion that
      slow (~25-55 Hz) and fast (~60-100 Hz) gamma are distinct network states with
      different functions. If slow and fast gamma constitute distinct network states,
      then it is possible that slow and fast gamma frequencies are differentially
      affected by running speed. In this study, we tested this hypothesis and found
      that slow and fast gamma frequencies change differently as a function of running
      speed in hippocampal areas CA1 and CA3, and in the superficial layers of the
      medial entorhinal cortex (MEC). Fast gamma frequencies increased with increasing
      running speed in all three areas. Slow gamma frequencies changed significantly
      less across different speeds. Furthermore, at high running speeds, CA3 firing
      rates were low, and MEC firing rates were high, suggesting that CA1 transitions
      from CA3 inputs to MEC inputs as running speed increases. These results support
      the hypothesis that slow and fast gamma reflect functionally distinct states in
      the hippocampal network, with fast gamma driven by MEC at high running speeds and
      slow gamma driven by CA3 at low running speeds.

PMID- 25601006
TI  - The notion of the motion: the neurocognition of motion lines in visual
      narratives.
AB  - Motion lines appear ubiquitously in graphic representation to depict the path of
      a moving object, most popularly in comics. Some researchers have argued that
      these graphic signs directly tie to the "streaks" appearing in the visual system
      when a viewer tracks an object (Burr, 2000), despite the fact that previous
      studies have been limited to offline measurements. Here, we directly examine the
      cognition of motion lines by comparing images in comic strips that depicted
      normal motion lines with those that either had no lines or anomalous, reversed
      lines. In Experiment 1, shorter viewing times appeared to images with normal
      lines than those with no lines, which were shorter than those with anomalous
      lines. In Experiment 2, measurements of event-related potentials (ERPs) showed
      that, compared to normal lines, panels with no lines elicited a posterior
      positivity that was distinct from the frontal positivity evoked by anomalous
      lines. These results suggested that motion lines aid in the comprehension of
      depicted events. LORETA source localization implicated greater activation of
      visual and language areas when understanding was made more difficult by anomalous
      lines. Furthermore, in both experiments, participants' experience reading comics
      modulated these effects, suggesting motion lines are not tied to aspects of the
      visual system, but rather are conventionalized parts of the "vocabulary" of the
      visual language of comics.

PMID- 25601007
TI  - A functional magnetic resonance imaging study on the effect of acupuncture at
      GB34 (Yanglingquan) on motor-related network in hemiplegic patients.
AB  - BACKGROUND: Functional disability of stroke patients, especially limb motor
      function, seriously impacts the quality of life. Although acupuncture at GB34
      (Yang-ling-quan) has been shown to be effective on the recovery of motor
      function, the underlying mechanism has not been well explored. OBJECTIVE: To
      explore the central mechanisms of immediate effect of acupuncture at GB34 on
      motor-related network of stroke patients with hemiplegia. METHODS: A repeated
      measures ANOVA method was employed to investigate the effect of acupuncture at
      GB34 on functional connectivity of motor-related network. Six stroke patients
      with left hemiplegia were recruited. A left hand motor task fMRI experiment was
      performed before and right after acupuncture. Sham point acupuncture was taken as
      control. The most significant fMRI signal changes during motor task in the right
      precentral gyrus were identified, which was selected as a seed point for
      connectivity analysis. Then the functional connectivity of this seed point was
      compared between verum and sham point acupuncture. RESULTS: Compared to sham,
      acupuncture at GB34 showed positive interaction effect at right temporal pole,
      left lingual gyrus, and left cerebellum. While negative interaction effect mainly
      occurred at contralateral motor cortex and ipsilateral motor cortex of lower
      limb. CONCLUSIONS: Acupuncture at GB34 may increase motor-cognition connectivity
      meanwhile decrease compensation of unaffected motor cortex and homolateral
      synkinesis, which can definitely promote the rehabilitation of hemiplegia and
      spasm.

PMID- 25601009
TI  - Protective effect of rhGLP-1 (7-36) on brain ischemia/reperfusion damage in
      diabetic rats.
AB  - In recent years, GLP-1 and its analogs have been developed for the treatment of
      type 2 diabetes. It has been reported that stimulating the GLP-1 receptor can
      protect neurons against metabolic and oxidative insults, and therefore can be
      used in the treatment of stroke and Parkinson's disease. The present study aimed
      to examine the neuroprotective effects of rhGLP-1 (7-36) and its possible
      mechanisms against acute ischemia/reperfusion injuries induced by middle cerebral
      artery occlusion (MCAO) in diabetic rats. The type 2 diabetic rat model was
      established by a combination of a high-fat diet and low-dose streptozotocin
      (STZ). RhGLP-1 (7-36) (20, 40, 80MUg/kg) was given intraperitoneally before
      reperfusion. The neuroprotective effects of rhGLP-1 (7-36) were evaluated by
      changes in neurological deficit scores and 2,3,5-Triphenyltetrazolium chloride
      (TTC) staining. Changes in blood glucose were used to assess hypoglycemic
      effects. The content of malondialdehyde (MDA) and the activities of superoxide
      dismutase (SOD), glutathione peroxidase (GSH-PX), inducible nitric oxide
      syntheses (iNOS) and endothelial nitric oxide syntheses (eNOS) after MCAO/R
      administration (2h and 46h) were examined to investigate the possible mechanisms
      of RhGLP-1 (7-36). Haematoxylin and eosin (H&E) staining was used for
      histopathological observation. Compared with the control group, rhGLP-1 (7-36)
      treated groups decreased nerve function deficiency scores; significantly reduced
      infarction volume percentage, MDA, iNOS and blood glucose; and significantly
      increased SOD, GSH-PX and eNOS. In addition, rhGLP-1 (7-36) groups enhanced the
      density of surviving neurons and increased vascular proliferation. The current
      study suggests a neuroprotective effect of rhGLP-1 (7-36) in diabetic MCAO/R rats
      since anti-oxidative and anti-nitrosative stress effects can contribute to
      beneficial effects against ischemia/reperfusion injury. 

PMID- 25601011
TI  - First nicastrin mutation in PASH (pyoderma gangrenosum, acne and suppurative
      hidradenitis) syndrome.

PMID- 25601010
TI  - Expression of ocular albinism 1 (OA1), 3, 4- dihydroxy- L-phenylalanine (DOPA)
      receptor, in both neuronal and non-neuronal organs.
AB  - Oa1 is the casual gene for ocular albinism-1 in humans. The gene product OA1,
      alternatively designated as GPR143, belongs to G-protein coupled receptors. It
      has been reported that OA1 is a specific receptor for 3, 4-dihydroxy- L
      phenylalanine (DOPA) in retinal pigmental epithelium where DOPA facilitates the
      pigmentation via OA1 stimulation. We have recently shown that OA1 mediates DOPA
      induced depressor response in rat nucleus tractus solitarii. However, the
      distribution and function of OA1 in other regions are largely unknown. We have
      generated oa1 knockout mice and examined OA1 expression in both neuronal and non
      neuronal tissues by immunohistochemical analyses using anti-mouse OA1 monoclonal
      antibodies. In the telencephalon, OA1 was expressed in cerebral cortex and
      hippocampus. Predominant expression of OA1 was observed in the pyramidal neurons
      in these regions. OA1 was also expressed in habenular nucleus, hypothalamus,
      substantia nigra, and medulla oblongata. The expression of OA1 in the nucleus
      tractus solitarii of medulla oblongata may support the reduction of blood
      pressure by the microinjection of DOPA into this region. Outside of the nervous
      system, OA1 was expressed in heart, lung, liver, kidney and spleen. Abundant
      expression was observed in the renal tubules and the splenic capsules. These
      peripheral regions are innervated by numerous sympathetic nerve endings. In
      addition, substantia nigra contains a large population of dopaminergic neurons.
      Thus, the immunohistochemical analyses suggest that OA1 may modulate the
      monoaminergic functions in both peripheral and central nervous systems. 

PMID- 25601012
TI  - Commissural localization of squamocellular carcinoma of the lip Our experience.
AB  - AIM: Lip cancer is the most common malignant tumour of the oral cavity and the
      oral commissure is the origin of the tumour in 6% to 8.5% of cases.
      Reconstruction of oral commissure defects aims at securing oral competence and
      providing an acceptable appearance. Satisfactory reconstruction of defects
      affecting the lip commissure is always challenging. MATERIAL OF STUDY: The
      authors present a selected group of 22 patients, who, between November 2005 and
      31st October 2012, underwent reconstruction for primary or secondary defects
      involving the oral commissure. RESULTS: The results were generally satisfactory,
      both functionally and cosmetically. The patients had been followed up for 5
      years. CONCLUSIONS: All patients had excellent oral competence during rest,
      speaking and eating. Good sphinteric function was obtained in early postoperative
      days. No drooling or air leakage. The aesthetic results were good in all
      patients.

PMID- 25601008
TI  - Females uniquely vulnerable to alcohol-induced neurotoxicity show altered
      glucocorticoid signaling.
AB  - Women are more sensitive to the harmful effects of alcohol (EtOH) abuse than men,
      yet the underlying mechanisms remain poorly understood. Previous gene expression
      analysis of the medial prefrontal cortex (mPFC) following a chronic intoxication
      paradigm using continuous 72 h vapor inhalation found that females, but not
      males, exhibit an inflammatory response at peak withdrawal that is associated
      with cell damage. Given that glucocorticoids can function as anti-inflammatories,
      are known to increase with EtOH exposure, and influence neurotoxicity, we
      hypothesized that males and females may exhibit an altered corticosterone (CORT)
      response following chronic intoxication. Analysis of serum CORT levels revealed
      the expected increase during withdrawal with no difference between males and
      females, while control males but not females exhibited higher CORT concentrations
      than naive animals. Glucocorticoid signaling characterized using focused qPCR
      arrays identified a sexually dimorphic response in the mPFC during withdrawal,
      particularly among astrocyte-enriched genes. These genes include aquaporin-1
      (Aqp1), sphingosine kinase 1 (Sphk1) and connective tissue growth factor (Ctgf);
      genes associated with inflammatory signaling, and tissue damage and repair.
      Bioinformatic analysis also revealed activation of inflammatory signaling and
      cell death pathways in females. Confirmation studies showed that female mice
      exhibited significant neuronal degeneration within the anterior cingulate cortex
      (ACC). By contrast, EtOH exposure lead to a significant reduction in cell death
      in males. Thus, distinct glucocorticoid signaling pathways are associated with
      sexually dimorphic neurotoxicity, suggesting one mechanism by which EtOH-exposed
      females are particularly vulnerable to the damaging effects of alcohol in the
      CNS.

PMID- 25601013
TI  - Population-Based Lynch Syndrome Screening by Microsatellite Instability in
      Patients <=50: Prevalence, Testing Determinants, and Result Availability Prior to
      Colon Surgery.
AB  - OBJECTIVES: As there are no US population-based studies examining Lynch syndrome
      (LS) screening frequency by microsatellite instability (MSI) and
      immunohistochemistry (IHC), we seek to quantitate statewide rates in patients
      aged <=50 years using data from a Centers for Disease Control and Prevention
      funded Comparative Effectiveness Research (CER) project and identify factors
      associated with testing. Screening rates in this young, high-risk population may
      provide a best-case scenario as older patients, potentially deemed lower risk,
      may undergo testing less frequently. We also seek to determine how frequently
      MSI/IHC results are available preoperatively, as this may assist with decisions
      regarding colonic resection extent. METHODS: Data from all Louisiana colorectal
      cancer (CRC) patients aged <=50 years diagnosed in 2011 were obtained from the
      Louisiana Tumor Registry CER project. Registry researchers and physicians
      analyzed data, including pathology and MSI/IHC. RESULTS: Of the 2,427 statewide
      all-age CRC patients, there were 274 patients aged <=50 years, representing
      health care at 61 distinct facilities. MSI and/or IHC were performed in 23.0% of
      patients. Testing-associated factors included CRC family history (P<0.0045),
      urban location (P<0.0370), and care at comprehensive cancer centers (P<0.0020)
      but not synchronous/metachronous CRC or MSI-like histology. Public hospital
      screening was disproportionately low (P<0.0217). Of those tested, MSI and/or IHC
      was abnormal in 21.7%. Of those with abnormal IHC, staining patterns were
      consistent with LS in 87.5%. MSI/IHC results were available preoperatively in
      16.9% of cases. CONCLUSIONS: Despite frequently abnormal MSI/IHC results, LS
      screening in young, high-risk patients is low. Provider education and disparities
      in access to specialized services, particularly in underserved populations, are
      possible contributors. MSI/IHC results are infrequently available preoperatively.

PMID- 25601015
TI  - Gender differences in patients with first-episode psychosis in the Singapore
      Early Psychosis Intervention Programme.
AB  - AIMS: This study aimed to identify the gender differences among multi-ethnic,
      Asian patients with first-episode psychosis attending the Early Psychosis
      Intervention Programme (EPIP) in Singapore. METHODS: Data for this study were
      derived from 533 (258 female, 275 male) patients aged 16-41 years old in the EPIP
      database. Socio-demographic data, Positive and Negative Syndrome Scale for
      schizophrenia (PANSS) and Global Assessment of Functioning (GAF) scores at
      baseline, 3 months, 6 months and 1 year were obtained. RESULTS: Significant
      gender differences were identified in terms of age, marital status, referral
      source, PANSS scores, GAF scores, remission and recovery over 1 year in the
      cohort. At service entry, female participants were older, more likely to be
      married and more likely to be referred from general practitioner/polyclinics (P <
      0.0001). They showed better improvement over 1 year in PANSS positive, PANSS
      total, GAF disability and GAF total scores. CONCLUSIONS: Overall, female
      participants in this sample show better improvement than male participants. They
      showed a better course of illness over 1 year with one-third (33.3%) of female
      participants achieving recovery compared with approximately a quarter (23.6%) of
      male participants.

PMID- 25601014
TI  - Impact of chromoscopy on adenoma detection in patients with Lynch syndrome: a
      prospective, multicenter, blinded, tandem colonoscopy study.
AB  - OBJECTIVES: In Lynch syndrome, flat and diminutive adenomas are particularly
      prone to malignant transformation, but they can be missed by standard
      colonoscopy. It is not known whether chromocolonoscopy is able to detect more
      adenomas than standard colonoscopy in patients with Lynch syndrome. METHODS: We
      conducted a prospective, multicenter, randomized trial to compare standard
      colonoscopy with standard colonoscopy followed by pancolonic chromoscopy with
      indigo carmine in patients with a proven germline mutation in a mismatch-repair
      gene related to Lynch syndrome and who were undergoing screening or surveillance
      colonoscopy. Standard colonoscopy was used first to detect visible lesions.
      Colonoscopy with chromoscopy was then performed by a second gastroenterologist
      (blinded to the findings of the first colonoscopy) to detect additional lesions.
      The primary end point was the number of patients in whom at least one adenoma was
      detected. RESULTS: A total of 78 eligible patients (median age, 45 years) were
      enrolled at 10 centers from July 2008 to August 2009. Significantly more patients
      with at least one adenoma were identified by chromocolonoscopy (32/78 (41%)) than
      by standard colonoscopy (18/78 (23%); P<0.001). The percentage of patients in
      whom at least one additional adenoma was detected during the chromoscopy was 31%
      (24/78). Overall, chromocolonoscopy plus colonoscopy detected a total of 55
      adenomas in 32 patients (mean number of adenomas detected per patient: 0.7 vs.
      standard colonoscopy alone: 0.3; P<0.001). CONCLUSION: The results support the
      proposition that chromocolonoscopy may significantly improve the detection rate
      of colorectal adenomas in patients undergoing screening or surveillance
      colonoscopy for Lynch syndrome.

PMID- 25601016
TI  - Immediate effects of Kinesio Taping((r)) on neuromuscular performance of
      quadriceps and balance in individuals submitted to anterior cruciate ligament
      reconstruction: A randomized clinical trial.
AB  - OBJECTIVES: Investigate the immediate effects of Kinesio Taping((r)) on
      neuromuscular performance of femoral quadriceps and balance in individuals
      submitted to anterior cruciate ligament reconstruction. DESIGN: This is a
      randomized clinical trial. METHODS: Forty-seven male participants, between 12 and
      17 weeks after anterior cruciate ligament reconstruction, underwent initial
      assessment consisting of postural balance analysis using baropodometry, followed
      by eccentric and concentric isokinetic assessment at 60 degrees /s of knee
      extensors, concomitant to electromyographic signals captured from the vastus
      lateralis muscle. They were then randomly allocated to one of the following
      groups: control, placebo and Kinesio Taping((r)). Kinesio Taping((r)) group
      participants were submitted to Kinesio Taping((r)) on the femoral quadriceps of
      the affected limb, while placebo group subjects used the same procedure without
      the tension proposed by the method. The control group remained at rest for 10min.
      All participants were reassessed following the same procedure as the initial
      evaluation. The following variables were analyzed: peak torque/body weight and
      muscle potential using dynamometry; amplitude of antero-posterior and latero
      lateral displacement from the center of pressure using baropodometry; and
      amplitude of muscle activation (root mean square) applying surface
      electromyography. RESULTS: None of the variables analyzed showed significant
      intergroup or intragroup differences. CONCLUSIONS: Kinesio Taping((r)) does not
      alter the neuromuscular performance of femoral quadriceps or balance of subjects
      submitted to anterior cruciate ligament reconstruction, for any of the variables
      analyzed.

PMID- 25601017
TI  - Introduction. DNA in Forensics 2014,.

PMID- 25601018
TI  - Use of expert relevancy ratings to validate task-specific search strategies for
      electronic medical records.
AB  - As electronic medical records (EMRs) grow in size and complexity, there is
      increasing need for automated EMR tools that highlight the medical record items
      most germane to a practitioner's task-specific needs. The development of such
      tools would be aided by gold standards of information relevance for a series of
      different clinical scenarios. We have previously proposed a process in which
      exemplar medical record data are extracted from actual patients' EMRs,
      anonymized, and presented to clinical experts, who then score each medical record
      item for its relevance to a specific clinical scenario. In this paper, we present
      how that body of expert relevancy data can be used to create a test framework to
      validate new EMR search strategies. 

PMID- 25601019
TI  - Effects of motor action on affective preferences in autism spectrum disorders:
      different influences of embodiment.
AB  - In the embodied cognition framework, sensory, motor and emotional experiences are
      encoded along with sensorimotor cues from the context in which information was
      acquired. As such, representations retain an initial imprint of the manner in
      which information was acquired. The current study reports results indicating a
      lack of embodiment effects in ASD and, further, an association between embodiment
      differences and ASD symptomatology. The current results are consistent with an
      embodied account of ASD that goes beyond social experiences and could be driven
      by subtle deficits in sensorimotor coordination.

PMID- 25601021
TI  - Correction to Differential diagnosis of vertical root fractures using
      reconstructed three-dimensional models of bone defects.

PMID- 25601020
TI  - High peak alanine aminotransferase determines extra risk for nonanastomotic
      biliary strictures after liver transplantation with donation after circulatory
      death.
AB  - Orthotopic liver transplantation (OLT) with donation after circulatory death
      (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and
      a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation
      after brain death (DBD). This retrospective study was to evaluate whether an
      association exists between peak ALT and the development of NAS in OLT with livers
      from DBD (n = 399) or DCD (n = 97) from two transplantation centers. Optimal
      cutoff value of peak ALT for risk of development of NAS post-DCD-OLT was 1300
      IU/l. The 4-year cumulative incidence of NAS after DCD-OLT was 49.5% in patients
      with a high ALT peak post-OLT, compared with 11.3% in patients with a low ALT
      peak. (P < 0.001). No relation between peak ALT and NAS was observed after DBD
      OLT. Multivariate analysis revealed peak ALT >=1300 IU/l [adjusted hazard ratio
      (aHR) = 3.71, confidence interval (CI) (1.26-10.91)] and donor age [aHR = 1.04,
      CI 1.00-1.07] to be independently associated with development of NAS post-DCD
      OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD-OLT. Thus, in
      DCD-OLT, but not in DBD-OLT, peak ALT discriminates patients at high or low risk
      for NAS. 

PMID- 25601024
TI  - Structural and biochemical characterization of VIM-26 shows that Leu224 has
      implications for the substrate specificity of VIM metallo-beta-lactamases.
AB  - During the last decades antimicrobial resistance has become a global health
      problem. Metallo-beta-lactamases (MBLs) which are broad-spectrum beta-lactamases
      that inactivate virtually all beta-lactams including carbapenems, are
      contributing to this health problem. In this study a novel MBL variant, termed
      VIM-26, identified in a Klebsiella pneumoniae isolate was studied. VIM-26 belongs
      to the Verona integron-encoded metallo-beta-lactamase (VIM) family of MBLs and is
      a His224Leu variant of the well-characterized VIM-1 variant. In this study, we
      report the kinetic parameters, minimum inhibitory concentrations and crystal
      structures of a recombinant VIM-26 protein, and compare them to previously
      published data on VIM-1, VIM-2 and VIM-7. The kinetic parameters and minimum
      inhibitory concentration determinations show that VIM-26, like VIM-7, has higher
      penicillinase activity but lower cephalosporinase activity than VIM-1 and VIM-2.
      The four determined VIM-26 crystal structures revealed mono- and di-zinc forms,
      where the Zn1 ion has distorted tetrahedral coordination geometry with an
      additional water molecule (W2) at a distance of 2.6-3.7 A, which could be
      important during catalysis. The R2 drug binding site in VIM-26 is more open
      compared to VIM-2 and VIM-7 and neutrally charged due to Leu224 and Ser228. Thus,
      the VIM-26 drug binding properties are different from the VIM-2 (Tyr224/Arg228)
      and VIM-7 (His224/Arg228) structures, indicating a role of these residues in the
      substrate specificity. 

PMID- 25601023
TI  - Comparative RNA-Seq analysis reveals pervasive tissue-specific alternative
      polyadenylation in Caenorhabditis elegans intestine and muscles.
AB  - BACKGROUND: Tissue-specific RNA plasticity broadly impacts the development,
      tissue identity and adaptability of all organisms, but changes in composition,
      expression levels and its impact on gene regulation in different somatic tissues
      are largely unknown. Here we developed a new method, polyA-tagging and sequencing
      (PAT-Seq) to isolate high-quality tissue-specific mRNA from Caenorhabditis
      elegans intestine, pharynx and body muscle tissues and study changes in their
      tissue-specific transcriptomes and 3'UTRomes. RESULTS: We have identified
      thousands of novel genes and isoforms differentially expressed between these
      three tissues. The intestine transcriptome is expansive, expressing over 30% of
      C. elegans mRNAs, while muscle transcriptomes are smaller but contain
      characteristic unique gene signatures. Active promoter regions in all three
      tissues reveal both known and novel enriched tissue-specific elements, along with
      putative transcription factors, suggesting novel tissue-specific modes of
      transcription initiation. We have precisely mapped approximately 20,000 tissue
      specific polyadenylation sites and discovered that about 30% of transcripts in
      somatic cells use alternative polyadenylation in a tissue-specific manner, with
      their 3'UTR isoforms significantly enriched with microRNA targets. CONCLUSIONS:
      For the first time, PAT-Seq allowed us to directly study tissue specific gene
      expression changes in an in vivo setting and compare these changes between three
      somatic tissues from the same organism at single-base resolution within the same
      experiment. We pinpoint precise tissue-specific transcriptome rearrangements and
      for the first time link tissue-specific alternative polyadenylation to miRNA
      regulation, suggesting novel and unexplored tissue-specific post-transcriptional
      regulatory networks in somatic cells.

PMID- 25601025
TI  - Photoprotection in sequestered plastids of sea slugs and respective algal
      sources.
AB  - Some sea slugs are capable of retaining functional sequestered chloroplasts
      (kleptoplasts) for variable periods of time. The mechanisms supporting the
      maintenance of these organelles in animal hosts are still largely unknown. Non
      photochemical quenching (NPQ) and the occurrence of a xanthophyll cycle were
      investigated in the sea slugs Elysia viridis and E. chlorotica using chlorophyll
      fluorescence measurements and pigment analysis. The photoprotective capacity of
      kleptoplasts was compared to that observed in their respective algal source,
      Codium tomentosum and Vaucheria litorea. A functional xanthophyll cycle and a
      rapidly reversible NPQ component were found in V. litorea and E. chlorotica but
      not in C. tomentosum and E. viridis. To our knowledge, this is the first report
      of the absence of a functional xanthophyll cycle in a green macroalgae. The
      absence of a functional xanthophyll cycle in C. tomentosum could contribute to
      the premature loss of photosynthetic activity and relatively short-term retention
      of kleptoplasts in E. viridis. On the contrary, E. chlorotica displays one of the
      longest functional examples of kleptoplasty known so far. We speculate that
      different efficiencies of photoprotection and repair mechanisms of algal food
      sources play a role in the longevity of photosynthetic activity in kleptoplasts
      retained by sea slugs. 

PMID- 25601026
TI  - Inhibition of KCa3.1 by depolarisation and 2-aminoethoxydiphenyl borate (2-APB)
      during Ca2+ release activated Ca2+ (CRAC) entry in human erythroleukemia (HEL)
      cells: Implications for the interpretation of 2-APB inhibition of CRAC entry.
AB  - In the present experiments in HEL cells, we have investigated the requirement for
      a hyperpolarised resting membrane potential for the initial activation of the
      Ca(2+) activated K(+) channel, KCa3.1, following activation of the Ca(2+) release
      activated Ca(2+) (CRAC) entry pathway. In intact cells, fluorimetric measurements
      of [Ca(2+)]i following thapsigargin-mediated activation of CRAC entry revealed a
      sustained increase in [Ca(2+)]i. Block of KCa3.1 by application of charybdotoxin
      resulted in a 50% reduction in the steady-state [Ca(2+)]i, consistent with the
      well established role for KCa3.1-mediated hyperpolarisation in augmenting CRAC
      entry. Interestingly, subsequent depolarisation to 0mV by application of
      gramicidin resulted in a fall in steady-state Ca(2+) levels to values
      theoretically below that required for activation of KCa3.1. Whole cell patch
      clamp experiments confirmed the lack of KCa3.1 activation at 0mV following
      activation of the CRAC entry pathway, indicating an absolute requirement for a
      hyperpolarised resting membrane potential for the initial activation of KCa3.1
      leading to hyperpolarisation and augmented Ca(2+) entry. Current clamp
      experiments confirmed the requirement for a hyperpolarised resting membrane
      potential in KCa3.1 activation by CRAC entry. Given the critical role played by
      KCa3.1 and membrane potential in general in the control of CRAC-mediated
      [Ca(2+)]i changes, we investigated the hypothesis that inhibition of the CRAC
      mediated changes in [Ca(2+)]i observed following 2-APB addition may in part arise
      from direct inhibition of KCa3.1 by 2-APB. Under whole cell patch clamp, 2-APB,
      at concentrations typically used to block the CRAC channel, potently inhibited
      KCa3.1 in a reversible manner (half maximal inhibition 14.2 MUM). This block was
      accompanied by a marked shift in the reversal potential to depolarised values
      approaching that set by endogenous membrane conductances. At the single channel
      level, 2-APB applied to the cytosolic face resulted in a significant reduction in
      open channel probability and a fall in the mean open time of the residual channel
      activity. Our data highlight the absolute requirement for a hyperpolarising
      resting membrane conductance for the initial activation of KCa3.1 by CRAC entry.
      Additionally, our results document direct inhibition of KCa3.1 by 2-APB, thus
      highlighting the need for caution when ascribing the site of inhibition of 2-APB
      exclusively to the CRAC entry pathway in experiments where membrane potential is
      not controlled.

PMID- 25601027
TI  - Molecular aspects of calcium signalling at the crossroads of unikont and bikont
      eukaryote evolution--the ciliated protozoan Paramecium in focus.
AB  - The ciliated protozoan, Paramecium tetraurelia has a high basic Ca(2+) leakage
      rate which is counteracted mainly by export through a contractile vacuole
      complex, based on its V-type H(+)-ATPase activity. In addition Paramecium cells
      dispose of P-type Ca(2+)-ATPases, i.e. a plasmamembrane and a
      sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (PMCA, SERCA). Antiporter
      systems are to be expected, as inferred from indirect evidence. Among the best
      known cytosolic Ca(2+)-binding proteins, calmodulin activates Ca(2+) influx
      channels in the somatic cell membrane, but inactivates Ca(2+) influx channels in
      cilia, where it, thus, ends ciliary reversal induced by depolarization via
      channels in the somatic cell membrane. Centrin inactivates Ca(2+) signals after
      stimulation by its high capacity/low affinity binding sites, whereas its high
      affinity sites regulate some other functions. Cortical Ca(2+) stores (alveolar
      sacs) are activated during stimulated trichocyst exocytosis and thereby mediate
      store-operated Ca(2+) entry (SOCE). Ca(2+) release channels (CRCs) localised to
      alveoli and underlying SOCE are considered as Ryanodine receptor-like proteins
      (RyR-LPs) which are members of a CRC family with 6 subfamilies. These also
      encompass genuine inositol 1,4,5-trisphosphate receptors (IP3Rs) and
      intermediates between the two channel types. All IP3R/RyR-type CRCs possess six
      carboxyterminal transmembrane domains (TMD), with a pore domain between TMD 5 and
      6, endowed with a characteristic selectivity filter. There are reasons to assume
      a common ancestor molecule for such channels and diversification further on in
      evolution. The distinct distribution of specific CRCs in the different vesicles
      undergoing intracellular trafficking suggests constitutive formation of very
      locally restricted Ca(2+) signals during vesicle-vesicle interaction. In summary,
      essential steps of Ca(2+) signalling already occur at this level of evolution,
      including an unexpected multitude of CRCs. For dis-/similarities with other
      bikonts see "Conclusions". 

PMID- 25601028
TI  - PFKFB4 controls embryonic patterning via Akt signalling independently of
      glycolysis.
AB  - How metabolism regulators play roles during early development remains elusive.
      Here we show that PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
      4), a glycolysis regulator, is critical for controlling dorsal ectoderm global
      patterning in gastrulating frog embryos via a non-glycolytic function. PFKFB4 is
      required for dorsal ectoderm progenitors to proceed towards more specified fates
      including neural and non-neural ectoderm, neural crest or placodes. This function
      is mediated by Akt signalling, a major pathway that integrates cell homeostasis
      and survival parameters. Restoring Akt signalling rescues the loss of PFKFB4 in
      vivo. In contrast, glycolysis is not essential for frog development at this
      stage. Our study reveals the existence of a PFKFB4-Akt checkpoint that links cell
      homeostasis to the ability of progenitor cells to undergo differentiation, and
      uncovers glycolysis-independent functions of PFKFB4. 

PMID- 25601029
TI  - Impact of Community Interventions on the Social Representation of Depression in
      Rural Gujarat.
AB  - There is a pressing need to develop community interventions that will address
      stigma against mental illness in rural India. This cross-sectional study will
      compare social representations of depression in villages where educational
      programs have targeted mental illness and stigma versus control villages.
      Participants from the villages exposed to the educational interventions (n = 146)
      will be compared with a sample from six control villages (n = 187) in the same
      geographic region, using a structured questionnaire. The impact of the
      intervention as a predictor for questionnaire score will be assessed along with
      socio-demographic variables. The intervention villages showed higher levels of
      literacy regarding depression and lower levels of stigma, after adjusting for all
      other socio-demographic variables. While some demographic factors associated with
      the knowledge and attitudes towards depression are not modifiable, our research
      provides evidence in favor of the positive influence a community grassroots
      intervention can have on mental health literacy in rural settings.

PMID- 25601030
TI  - The Polish Academic Version of the MATRICS Consensus Cognitive Battery (MCCB):
      Evaluation of Psychometric Properties.
AB  - Work and social functioning in schizophrenia are strongly influenced by cognitive
      impairment so improving cognition is a priority in the treatment of
      schizophrenia. Until recently the lack of a widely accepted index of cognitive
      change for use in schizophrenia was a major obstacle to the development of
      cognition enhancing treatments. The MATRICS (measurement and treatment research
      to improve cognition in schizophrenia) consensus cognitive battery (MCCB) was
      developed as a standard cognitive battery for use in clinical trials of cognition
      enhancing treatments for schizophrenia and has attracted worldwide interest. To
      analyze the reliability and validity of a translated and adapted Polish approved
      academic version of the MCCB. Sixty one patients were assessed at baseline and
      again after 30 days. The study protocol approximated the MATRICS psychometric and
      standardization study; the 10 tests that comprise the MCCB were administered to
      participants. Functioning and psychopathological symptoms were also assessed.
      Patients and test administrators also assessed the tolerability and practicality
      of all the cognitive tests. All tests in the battery were found to have high test
      retest reliability. All the tests were rated as tolerable and practical by
      patients and administrators. However practice effects were generally higher in
      the Polish version of the MCCB than in the original version. Our analysis
      corroborates previous evidence that the MCCB represents a good tool for assessing
      cognitive deficits in research studies of schizophrenia also in non-English
      speaking countries.

PMID- 25601031
TI  - Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through
      expression of caveolin-1.
AB  - Fatty acid-binding proteins (FABPs) bind and solubilize long-chain fatty acids,
      controlling intracellular lipid dynamics. FABP7 is expressed by astrocytes in the
      developing brain, and suggested to be involved in the control of astrocyte lipid
      homeostasis. In this study, we sought to examine the role of FABP7 in astrocytes,
      focusing on plasma membrane lipid raft function, which is important for receptor
      mediated signal transduction in response to extracellular stimuli. In FABP7
      knockout (KO) astrocytes, the ligand-dependent accumulation of Toll-like receptor
      4 (TLR4) and glial cell-line-derived neurotrophic factor receptor alpha 1 into
      lipid raft was decreased, and the activation of mitogen-activated protein kinases
      and nuclear factor-kappaB was impaired after lipopolysaccharide (LPS) stimulation
      when compared with wild-type astrocytes. In addition, the expression of caveolin
      1, not cavin-1, 2, 3, caveolin-2, and flotillin-1, was found to be decreased at
      the protein and transcriptional levels. FABP7 re-expression in FABP7-KO
      astrocytes rescued the decreased level of caveolin-1. Furthermore, caveolin-1
      transfection into FABP7-KO astrocytes significantly increased TLR4 recruitment
      into lipid raft and tumor necrosis factor-alpha production after LPS stimulation.
      Taken together, these data suggest that FABP7 controls lipid raft function
      through the regulation of caveolin-1 expression and is involved in the response
      of astrocytes to the external stimuli. GLIA 2015;63:780-794. 

PMID- 25601034
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical challenges in
      a changing disease spectrum.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an
      inherited cardiomyopathy characterized by fibro-fatty replacement of
      predominantly the right ventricle (RV), which predisposes patients to life
      threatening ventricular arrhythmias and usually slowly progressive ventricular
      dysfunction. The disease is inherited as an autosomal dominant trait with
      incomplete penetrance and variable expressivity. Increased appreciation of ARVD/C
      as a "disease of the desmosome" has fueled research into possible disease
      mechanisms, and insights into ARVD/C pathogenesis are rapidly advancing. Although
      ARVD/C is known to preferentially affect the RV, early and/or predominant left
      ventricular involvement is increasingly recognized. Diagnosis is made by
      combining multiple sources of diagnostic information as prescribed by the
      consensus-based Task Force criteria. Affected individuals typically present in
      the third to fifth decade of life with palpitations, lightheadedness, or syncope
      due to frequent ventricular ectopy or arrhythmias originating from the RV.
      However, disease expression is highly variable, even among subjects from the same
      family or those carrying the same mutation. Since sudden cardiac death can be the
      first manifestation of the disease, optimizing the approach to early detection
      and risk stratification of ARVD/C is of utmost importance. This review will
      discuss the changing spectrum of ARVD/C based on recent advances in diagnosis,
      genetics, and improved understanding of disease pathophysiology. 

PMID- 25601032
TI  - The myth of the "vulnerable plaque": transitioning from a focus on individual
      lesions to atherosclerotic disease burden for coronary artery disease risk
      assessment.
AB  - The cardiovascular science community has pursued the quest to identify vulnerable
      atherosclerotic plaque in patients for decades, hoping to prevent acute coronary
      events. However, despite major advancements in imaging technology that allow
      visualization of rupture-prone plaques, clinical studies have not demonstrated
      improved risk prediction compared with traditional approaches. Considering the
      complex relationship between plaque rupture and acute coronary event risk
      suggested by pathology studies and confirmed by clinical investigations, these
      results are not surprising. This review summarizes the evidence supporting a
      multifaceted hypothesis of the natural history of atherosclerotic plaque rupture.
      Managing patients at risk of acute coronary events mandates a greater focus on
      the atherosclerotic disease burden rather than on features of individual plaques.

PMID- 25601035
TI  - Prevention of cardiovascular disease.
AB  - Meaningful prevention of cardiovascular disease (CVD) requires prolongation of
      life to age 90 or 100 free of morbid events. This requires early detection of the
      CVD phenotypes and effective treatment to slow their progression. We present a
      strategy for screening and evaluation of the population that should accomplish
      that goal with potential benefits on both cost and cardiovascular health. Studies
      to document the effectiveness of this strategy are urgently needed. 

PMID- 25601036
TI  - From an evolutionary perspective, all 'new' antimicrobial targets are old: time
      to think outside the box.

PMID- 25601037
TI  - Meeting the societal need for new antibiotics: the challenges for the
      pharmaceutical industry.
AB  - The rise of antibiotic resistance is leading to clinicians being increasingly
      faced with clinical failure due to the lack of effective and safe treatment
      options. New antibiotics are needed now for current multi-drug resistant
      infections but also in preparation for emerging and anticipated threats. There
      are significant challenges for the pharmaceutical industry to discover and
      develop new antibiotics including a business model that balances reasonable
      reimbursement with appropriate use. This summary reviews the key challenges and
      collaborative interventions that may contribute to addressing a societal problem.

PMID- 25601038
TI  - Ancient human genomics: the methodology behind reconstructing evolutionary
      pathways.
AB  - High-throughput sequencing (HTS) has radically altered approaches to human
      evolutionary research. Recent contributions highlight that HTS is able to reach
      depths of the human lineage previously thought to be impossible. In this paper,
      we outline the methodological advances afforded by recent developments in DNA
      recovery, data output, scalability, speed, and resolution of the current
      sequencing technology. We review and critically evaluate the 'DNA pipeline' for
      ancient samples: from DNA extraction, to constructing immortalized sequence
      libraries, to enrichment strategies (e.g., polymerase chain reaction [PCR] and
      hybridization capture), and finally, to bioinformatic analyses of sequence data.
      We argue that continued evaluations and improvements to this process are
      essential to ensure sequence data validity. Also, we highlight the role of
      contamination and authentication in ancient DNA-HTS, which is particularly
      relevant to ancient human genomics, since sequencing the genomes of hominins such
      as Homo erectus and Homo heidelbergensis may soon be within the realm of
      possibility. 

PMID- 25601040
TI  - Supervised near-peer clinical teaching in the ambulatory clinic: an exploratory
      study of family medicine residents' perspectives.
AB  - Near-peer teaching is used extensively in hospital-based rotations but its use in
      ambulatory care is less well studied. The objective of this study was to verify
      the benefits of near-peer teaching found in other contexts and to explore the
      benefits and challenges of near-peer clinical supervision unique to primary care.
      A qualitative descriptive design using semi-structured interviews was chosen to
      accomplish this. A faculty preceptor supervised senior family medicine residents
      as they supervised a junior resident. We then elicited residents' perceptions of
      the experience. The study took place at a family medicine teaching unit in
      Canada. Six first-year and three second-year family medicine residents
      participated. Both junior and senior residents agreed that near-peer clinical
      supervision should be an option during family medicine residency training. The
      senior resident was perceived to benefit the most. Near-peer teaching was found
      to promote self-reflection and confidence in the supervising resident. Residents
      felt that observation by a faculty preceptor was required. In conclusion, the
      benefits of near-peer teaching previously described in hospital settings can be
      extended to ambulatory care training programmes. However, the perceived need for
      direct observation in a primary care context may make it more challenging to
      implement. 

PMID- 25601039
TI  - Rice stripe virus affects the viability of its vector offspring by changing
      developmental gene expression in embryos.
AB  - Plant viruses may affect the viability and development process of their herbivore
      vectors. Small brown planthopper (SBPH) is main vector of Rice stripe virus
      (RSV), which causes serious rice stripe disease. Here, we reported the effects of
      RSV on SBPH offspring by crossing experiments between viruliferous and non
      viruliferous strains. The life parameters of offspring from different cross
      combinations were compared. The hatchability of F1 progeny from viruliferous
      parents decreased significantly, and viruliferous rate was completely controlled
      by viruliferous maternal parent. To better elucidate the underlying biological
      mechanisms, the morphology of eggs, viral propagation and distribution in the
      eggs and expression profile of embryonic development genes were investigated. The
      results indicated that RSV replicated and accumulated in SBPH eggs resulting in
      developmental stunt or delay of partial eggs; in addition, RSV was only able to
      infect ovum but not sperm. According to the expression profile, expression of 13
      developmental genes was regulated in the eggs from viruliferous parents, in which
      two important regulatory genes (Ls-Dorsal and Ls-CPO) were most significantly
      down-regulated. In general, RSV exerts an adverse effect on SBPH, which is
      unfavourable for the expansion of viruliferous populations. The viewpoint is also
      supported by systematic monitoring of SBPH viruliferous rate. 

PMID- 25601042
TI  - "3 + 1 = 6 + 2" in Cu(II) coordination chemistry of 1H-pyrazole aza cryptands.
AB  - A polyazamacrocycle formed from two tris(2-aminoethyl)amine units connected by 1H
      pyrazole units shows unique hexanuclear Cu(ii) complexes by combination of two
      binuclear Cu(ii) cryptand complexes through pyrazolate moieties belonging to both
      cryptands. The formation of these dimeric entities has been proven both in
      solution by potentiometric studies and mass spectroscopy and in the solid state
      by X-ray diffraction of crystals of three different batches of formulae [Cu6(H
      3)2(H2O)2](TsO)6.22H2O (), [Cu6(H-3)2(NO3)2](NO3)4.2H2O () and [Cu6(H
      3)2Cl2]Cl4.(C4H5N3O2)2.14.35H2O (). The hexanuclear unit in and can be viewed
      like three magnetically independent binuclear complexes with J = -366(3) cm(-1),
      g = 2.08(1) for and J = -360(3) cm(-1), g = 2.07(1) for . 

PMID- 25601041
TI  - Normative biometrics for fetal ocular growth using volumetric MRI reconstruction.
AB  - OBJECTIVE: To determine normative ranges for fetal ocular biometrics between 19
      and 38 weeks gestational age (GA) using volumetric MRI reconstruction. METHOD:
      The 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created
      using super-resolution volume reconstructions from MRI slice acquisitions. These
      3D images were semi-automatically segmented to measure fetal orbit volume,
      binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD).
      RESULTS: All biometry correlated with GA (Volume, Pearson's correlation
      coefficient (CC) = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC =
      0.8429), and growth curves were plotted against linear and quadratic growth
      models. Regression analysis showed quadratic models to best fit BOD, IOD, and OD
      and a linear model to best fit volume. CONCLUSION: Orbital volume had the
      greatest correlation with GA, although BOD and OD also showed strong correlation.
      The normative data found in this study may be helpful for the detection of
      congenital fetal anomalies with more consistent measurements than are currently
      available. (c) 2015 John Wiley & Sons, Ltd.

PMID- 25601043
TI  - Comparison of treatment selections by Japanese and US psychiatrists for major
      depressive disorder: A case vignette study.
AB  - AIMS: A review of the published work on treatments for major depressive disorder
      suggests that there is an alarming gap between guideline recommendations and
      actual clinical practices worldwide. The purpose of this study was to compare
      early-career psychiatrists' selections of treatment for mild to moderate major
      depression in Japan and the USA. METHODS: The authors surveyed 120 early-career
      psychiatrists from two residency programs in Japan and the USA using web-based
      questionnaires. In response to two case vignettes of mild to moderate major
      depression, the subjects selected treatment modalities and first- and second-line
      pharmacotherapy. RESULTS: Eighty-one psychiatrists (68%) returned surveys, of
      whom 42 (52%) were Japanese and 39 (48%) American. Fewer Japanese subjects
      selected psychotherapy than Americans. The Japanese psychiatrists favored
      benzodiazepine monotherapy for the treatment of mild depression, whereas the
      American psychiatrists favored antidepressant monotherapy. For the initial
      treatment of moderate depression, approximately half of the Japanese selected
      antidepressant monotherapy, and a quarter selected benzodiazepine monotherapy,
      whereas the Americans unanimously selected selective serotonin reuptake
      inhibitors monotherapy. As a second-line strategy, the Japanese were more likely
      to augment medication and less likely to increase dosage for moderate depression
      than their American counterparts. CONCLUSIONS: Differences were found between the
      treatment selections of early-career psychiatrists in Japan and the USA, despite
      comparable guidelines and postgraduate training. The results suggest that the gap
      between guidelines and practice may also be shaped by physician workload,
      attitudes toward side-effects, and the sociocultural contexts in which clinical
      decisions are made.

PMID- 25601044
TI  - Fluorescent silver nanocluster DNA probes for multiplexed detection using
      microfluidic capillary electrophoresis.
AB  - DNA-stabilized fluorescent silver nanoclusters (AgNC DNA) are a new class of
      fluorophore that are formed by sequence specific interactions between silver and
      single-stranded DNA. By incorporating both target-binding and fluorescent
      reporting sequences into a single synthetic DNA oligomer, AgNC DNA probes
      eliminate the need to conjugate dye or quencher molecules. In this study, we
      modify a AgNC DNA probe to demonstrate single-color multiplexed detection of DNA
      targets. We show that appending different lengths of poly-dT to the probe
      sequences tunes the electrophoretic mobility of AgNC DNA probes without affecting
      their fluorescence spectra. We use this to introduce a set of AgNC DNA probes
      selective for Hepatitis A, B and C target sequences that can be processed
      together in a simple, single-step protocol and distinguished with a resolution of
      3.47 and signal to noise ratio of 17.23 in under 10 seconds by microfluidic
      capillary electrophoresis. 

PMID- 25601045
TI  - Novel device for expanding Schlemm's canal: a morphological study: Implantation
      of the Stegmann Canal Expander following viscodilation of Schlemm's canal
      resulted in permanent expansion of the canal lumen and distension of the
      trabecular meshwork without complications.
AB  - This study was performed to assess any changes in Schlemm's canal (SC) in human
      autopsy eyes possibly resulting from the injection of a viscoelastic substance
      and implantation of a new device (the Stegmann Canal Expander, SCE) into SC.
      After the surgical procedure, eyes were fixed, dissected into quartered segments
      and examined using light and scanning electron microscopy. Tissue sections
      displayed a marked dilation of SC and of the collector channels compared with
      untreated control sections. The SC walls were disrupted in some areas due to
      viscodilation, but not due to SCE implantation. In all eyes, the entire 9-mm
      length of the SCE was positioned inside the canal, keeping the canal wide open.
      The SCE diameter of 240 MUm remained unchanged after implantation. Injection of a
      viscoelastic substance into SC leads to marked dilation of SC and collector
      channels. Implanting the SCE into SC allowed persistent expansion of SC and
      stretching of the trabecular meshwork. This may increase the permeability of the
      trabecular meshwork, reduce its resistance to aqueous humour and maintain
      circumferential flow within SC. Experimental and clinical studies should
      determine the impact of this new canal expander in terms of lowering intraocular
      pressure in glaucoma surgery. 

PMID- 25601046
TI  - Zoledronate inhibits receptor activator of nuclear factor kappa-B ligand-induced
      osteoclast differentiation via suppression of expression of nuclear factor of
      activated T-cell c1 and carbonic anhydrase 2.
AB  - Bisphosphonates (BPs) are widely used in the prevention of skeletal-related
      events (SRE), including osteoporosis, skeletal metastases of malignant tumours,
      and multiple myeloma. Osteonecrosis of the jaw (ONJ) is frequently reported as a
      major adverse effect induced by BP treatment. The receptor activator of the
      nuclear factor kappa-B ligand (RANKL) inhibitor, denosumab, has recently been
      used to prevent SRE, but the frequency of ONJ induced by denosumab is similar to
      that by BPs. This finding suggests that the inhibition of RANKL-mediated
      osteoclastogenesis may have a close relationship with the occurrence of ONJ. We
      therefore investigated the expression status of RANKL-inducible genes in
      zoledronate-treated mouse osteoclast precursor cells. The molecular targets of
      zoledronate in the RANKL signal pathway and additional factors associated with
      osteoclastogenesis were analysed by genome-wide screening. Microarray analysis
      identified that among 31 genes on 44 entities of RANKL-inducible genes, the mRNA
      expression level of two genes, i.e., nuclear factor of activated T-cells c1
      (NFATc1) and carbonic anhydrase 2 (CAII), was decreased in zoledronate-treated
      cells. Subsequent analyses verified that these two genes were significantly
      silenced by zoledronate treatment and that their expression was restored
      following inhibition of zoledronate action by geranylgeraniol. Zoledronate
      inhibited RANKL-induced osteoclast differentiation by suppression of NFATc1 and
      CAII gene expression. Our results suggest that these genes might be common
      targets for zoledronate and denosumab in the mechanism underlying RANKL-induced
      osteoclast differentiation. A clear understanding of the common molecular
      mechanisms of bone-remodelling agents is thus essential for prevention of ONJ. 

PMID- 25601047
TI  - Colwellia arctica sp. nov., isolated from Arctic marine sediment.
AB  - Strain 435(T), a catalase- and oxidase-positive, beige-pigmented, facultatively
      anaerobic and Gram-stain-negative marine bacterium, was isolated from marine
      sediment collected in the Arctic (8 degrees 21'629''E 72 degrees 8'827''N). The
      cells of the type strain are short- to curve-rods and able to grow at 4-25 
      degrees C, pH 6.0-9.0 and in the presence of 0.5-6.0 % (w/v) NaCl. It can reduce
      nitrate to nitrite. The predominant isoprenoid quinone was identified as Q-8 and
      the polar lipids are comprised of phosphatidylethanolamine and
      phosphatidylglycerol. The DNA G+C content is 38.7 mol%. Phylogenetic analysis
      based on 16S rRNA gene sequences revealed that strain 435(T) belongs to the genus
      Colwellia. Strain 435(T) was found to exhibit 92.1-95.6 % 16S rRNA gene sequence
      similarities with other species of the genus Colwellia. The differential
      phenotypic properties, together with the phylogenetic and genetic distinctiveness
      indicated that strain 435(T) can be considered to represent a novel species,
      Colwellia arctica sp. nov., of the genus Colwellia. The type strain is 435(T)
      (=CICC 10860(T) = ATCC BAA-2609(T)). 

PMID- 25601048
TI  - Relationship between honeybee nutrition and their microbial communities.
AB  - The microbiota and the functional genes actively involved in the process of
      breakdown and utilization of pollen grains in beebread and bee guts are not yet
      understood. The aim of this work was to assess the diversity and community
      structure of bacteria and archaea in Africanized honeybee guts and beebread as
      well as to predict the genes involved in the microbial bioprocessing of pollen
      using state of the art 'post-light' based sequencing technology. A total of 11
      bacterial phyla were found within bee guts and 10 bacterial phyla were found
      within beebread. Although the phylum level comparison shows most phyla in common,
      a deeper phylogenetic analysis showed greater variation of taxonomic composition.
      The families Enterobacteriaceae, Ricketsiaceae, Spiroplasmataceae and
      Bacillaceae, were the main groups responsible for the specificity of the bee gut
      while the main families responsible for the specificity of the beebread were
      Neisseriaceae, Flavobacteriaceae, Acetobacteraceae and Lactobacillaceae. In terms
      of microbial community structure, the analysis showed that the communities from
      the two environments were quite different from each other with only 7 % of
      species-level taxa shared between bee gut and beebread. The results indicated the
      presence of a highly specialized and well-adapted microbiota within each bee gut
      and beebread. The beebread community included a greater relative abundance of
      genes related to amino acid, carbohydrate, and lipid metabolism, suggesting that
      pollen biodegradation predominantly occurs in the beebread. These results
      suggests a complex and important relationship between honeybee nutrition and
      their microbial communities. 

PMID- 25601049
TI  - Antibiotic residue monitoring results for pork, chicken, and beef samples in
      Vietnam in 2012-2013.
AB  - A monitoring plan of residual antibiotics in food of animal origin was conducted
      in Vietnam from 2012 to 2013. Meat samples were collected from slaughterhouses
      and retail stores in Ho Chi Minh City and Nha Trang. A total of 28 antibiotics
      were analyzed using a LC-MS/MS screening method. Sulfonamides, fluoroquinolones,
      and tilmicosin were detected in some of the samples. Sulfaclozine and
      fluoroquinolones were mainly detected in chicken samples, and sulfamethazine was
      mainly detected in pork samples. High levels of sulfonamide residues, ranging
      between 2500 and 2700 MUg/kg sulfaclozine and between 1300 and 3600 MUg/kg
      sulfamethazine, were present in two chicken and three pork samples, respectively.
      Tilmicosin was detected at ranges of 150-450 MUg/kg in 10 chicken samples.
      Positive percentages were 17.3, 8.8, and 7.4% for chicken, pork, and beef,
      respectively, for an average of 11.9%. The results suggest an appropriate
      withdrawal period after drug administration had not been observed in some
      livestock. 

PMID- 25601050
TI  - A fuzzy-match search engine for physician directories.
AB  - BACKGROUND: A search engine to find physicians' information is a basic but
      crucial function of a health care provider's website. Inefficient search engines,
      which return no results or incorrect results, can lead to patient frustration and
      potential customer loss. A search engine that can handle misspellings and
      spelling variations of names is needed, as the United States (US) has culturally,
      racially, and ethnically diverse names. OBJECTIVE: The Marshfield Clinic website
      provides a search engine for users to search for physicians' names. The current
      search engine provides an auto-completion function, but it requires an exact
      match. We observed that 26% of all searches yielded no results. The goal was to
      design a fuzzy-match algorithm to aid users in finding physicians easier and
      faster. METHODS: Instead of an exact match search, we used a fuzzy algorithm to
      find similar matches for searched terms. In the algorithm, we solved three types
      of search engine failures: "Typographic", "Phonetic spelling variation", and
      "Nickname". To solve these mismatches, we used a customized Levenshtein distance
      calculation that incorporated Soundex coding and a lookup table of nicknames
      derived from US census data. RESULTS: Using the "Challenge Data Set of Marshfield
      Physician Names," we evaluated the accuracy of fuzzy-match engine-top ten (90%)
      and compared it with exact match (0%), Soundex (24%), Levenshtein distance (59%),
      and fuzzy-match engine-top one (71%). CONCLUSIONS: We designed, created a
      reference implementation, and evaluated a fuzzy-match search engine for physician
      directories. The open-source code is available at the codeplex website and a
      reference implementation is available for demonstration at the datamarsh website.

PMID- 25601051
TI  - Gender differences in the human brain.

PMID- 25601057
TI  - Three-year risk of cardiovascular disease among intensive care patients with
      acute kidney injury: a population-based cohort study.
AB  - INTRODUCTION: Acute kidney injury (AKI) is common among intensive care unit (ICU)
      patients, but follow-up data on subsequent risk of cardiovascular disease remain
      sparse. We examined the impact of AKI on three-year risk of first-time heart
      failure, myocardial infarction (MI), and stroke among ICU patients surviving to
      hospital discharge, and whether this risk is modified by renal recovery before
      hospital discharge. METHODS: We used population-based medical registries to
      identify all adult patients admitted to an ICU in Northern Denmark between 2005
      and 2010 who survived to hospital discharge and who had no previous or concurrent
      diagnosis of heart failure, MI, or stroke. AKI was defined according to the
      creatinine criteria in the Kidney Disease Improving Global Outcomes
      classification. We computed the three-year cumulative risk of hospitalization
      with heart failure, MI, and stroke for patients with and without AKI and the
      hazard ratios (HRs), using a Cox model adjusted for potential confounders.
      RESULTS: Among 21,556 ICU patients surviving to hospital discharge, 4,792 (22.2%)
      had an AKI episode. Three-year cumulative risk of heart failure was 2.2% in
      patients without AKI, 5.0% for AKI stage 1, and 5.0% for stages 2 to 3. The
      corresponding adjusted HRs were 1.33 (95% confidence interval (CI), 1.06 to 1.66)
      for patients with AKI stage 1 and 1.45 (95% CI, 1.14 to 1.84) for AKI stages 2 to
      3, compared to patients without AKI. The three-year cumulative MI risk was 1.0%
      for patients without AKI, 1.8% for patients with AKI stage 1 and 2.3% for
      patients with AKI stages 2 to 3. The adjusted HR for MI was 1.04 (95% CI, 0.71 to
      1.51) for patients with AKI stage 1 and 1.51 (95% CI, 1.05 to 2.18) for patients
      with AKI stages 2 to 3, compared with patients without AKI. We found no
      association between AKI and stroke. The increased risk of heart failure and MI
      persisted in patients with renal recovery before discharge, although it was less
      pronounced than in patients without renal recovery. CONCLUSIONS: ICU patients
      surviving any stage of AKI are at increased three-year risk of heart failure, but
      not stroke. Only AKI stages 2 to 3 are associated with increased MI risk.

PMID- 25601058
TI  - Melatonin reduces lead levels in blood, brain and bone and increases lead
      excretion in rats subjected to subacute lead treatment.
AB  - Melatonin, a hormone known for its effects on free radical scavenging and
      antioxidant activity, can reduce lead toxicity in vivo and in vitro.We examined
      the effects of melatonin on lead bio-distribution. Rats were intraperitoneally
      injected with lead acetate (10, 15 or 20mg/kg/day) with or without melatonin
      (10mg/kg/day) daily for 10 days. In rats intoxicated with the highest lead doses,
      those treated with melatonin had lower lead levels in blood and higher levels in
      urine and feces than those treated with lead alone, suggesting that melatonin
      increases lead excretion. To explore the mechanism underlying this effect, we
      first assessed whether lead/melatonin complexes were formed directly. Electronic
      density functional (DFT) calculations showed that a lead/melatonin complex is
      energetically feasible; however, UV spectroscopy and NMR analysis showed no
      evidence of such complexes. Next, we examined the liver mRNA levels of
      metallothioneins (MT) 1 and 2. Melatonin cotreatment increased the MT2 mRNA
      expression in the liver of rats that received the highest doses of lead. The
      potential effects of MTs on the tissue distribution and excretion of lead are not
      well understood. This is the first report to suggest that melatonin directly
      affects lead levels in organisms exposed to subacute lead intoxication. 

PMID- 25601059
TI  - Posterior fossa tumor with distinct choroid plexus papilloma and ependymoma
      components.
AB  - Synchronous occurrence of multiple primary central nervous system (CNS) tumors of
      different histological types is uncommon in patients without radiation history or
      genetic syndrome association. We herein report a sporadic case of posterior fossa
      tumor with synchronous choroid plexus papilloma (CPP) and ependymoma (EP)
      components. A 7-year-old girl with no significant past or familial medical
      history presented with 2 years of migraine type headaches. Brain magnetic
      resonance imaging showed a cystic mass with a mural enhancing nodule centered
      within the cerebellar vermis. The patient underwent gross total resection of the
      tumor. Histologic examination showed a tumor with two distinct components. The
      predominant component demonstrated classic morphological and immunohistochemical
      characteristics of choroid plexus papilloma CPP, WHO grade I. However, there were
      a few discrete foci, where tumor cells showed architectural, cytological, and
      immunohistochemical features characteristic of an ependymoma, WHO grade II. In
      addition, there was exuberant piloid gliosis secondary to infiltration of the CPP
      component into the adjacent brain parenchyma. Followup brain imaging at 14 months
      after surgery showed no evidence of residual or recurrent tumor. To the best of
      our knowledge, this is the first reported case of synchronous CPP and EP in the
      posterior fossa. 

PMID- 25601060
TI  - Focal cortical dysplasia in meningioangiomatosis.
AB  - Meningioangiomatosis is a rare, benign, developmental, or hamartomatous lesion
      which may involve the leptomeninges and underlying brain parenchyma.
      Histologically, meningioangiomatosis is marked by a proliferation of blood
      vessels in the parenchyma, rimmed by collars of spindled meningothelial cells.
      There are anecdotal reports of an association of meningioangiomatosis with focal
      cortical dysplasia. We retrospectively analyzed the clinical, histopathologic,
      and treatment outcomes of 16 patients with a diagnosis of meningioangiomatosis,
      specifically investigating these cases for evidence of adjacent focal cortical
      dysplasia. Patients ranged in age from 1 to 34 years (median 18), 12 of whom had
      medically-intractable epilepsy as their presenting symptom. No patients in this
      study had a confirmed diagnosis of neurofibromatosis type II. Four patients (25%)
      were found to have fibrous meningiomas associated with the meningioangiomatosis.
      Ten of the 12 patients (83%) who had adequate tissue excised adjacent to the
      meningioangiomatosis demonstrated evidence of focal cortical dysplasia, with 6 of
      those (60%) classified as Palmini type IA, and 4 patients (40%) classified as
      Palmini type IIA. Seven of the patients (44%) had no post-operative seizures, and
      were off anti-epileptic drugs, while 2 patients relapsed, and required
      pharmacologic treatment for seizure control. This study therefore presents
      evidence to support inclusion of meningioangiomatosis as a focal cortical
      dysplasia-associated entity, as suggested by the ILAE classification (type IIIc).
      As focal cortical dysplasia is a developmental malformation, its association with
      meningioangiomatosis supports a developmental etiology of sporadic
      meningioangiomatosis. 

PMID- 25601061
TI  - Spontaneous passage of long, sharp gastrointestinal foreign body in a child.
AB  - Foreign body (FB) ingestion is a common problem in children. Up to 90% of these
      FBs pass spontaneously. FBs reaching the stomach usually pass out spontaneously.
      Exceptions to this spontaneous passage include a long FB that cannot cross the
      pylorus, duodenum or ileocaecal junction. We present a case of a 9-year boy who
      accidentally ingested a long paper pin, which spontaneously passed in 26 h. This
      case is being reported to highlight the successful spontaneous passage of a 4 cm
      long sharp foreign body in a child.

PMID- 25601062
TI  - Disulphide-thiol chemistry: a multi-faceted tool for macromolecular design and
      synthesis of polyfunctional materials for specialized drug delivery.
AB  - This review highlights recent interests and applications of disulphide and thiol
      chemistry in creating contemporary macromolecular designs. Due to the chemical
      nature of disulphides and thiols a wide range of chemical species react with
      these functional groups to yield a variety of polymers extending their
      applications in chemical, biological, physical, material engineering and material
      sciences. The review aims to illustrate the versatility and demonstrate the
      potential of thiol-based chemistries. The focus is on exploring bio-cleavable
      disulphides and linking by "clicking" thiols via thiol/other functional group
      exchange reactions. Thiol synthesis, modification and functionalization are
      demonstrated to be highly attractive and efficient in polymer and material
      science which in turn have immense application in biological therapeutics and
      drug delivery. The review also illustrates the remarkable pliability of synthetic
      and natural approaches to designing, optimizing and functionalizing
      nanostructures and conjugates by thiol chermistry modification. The examples
      quoted in the review illustrate the power and versatility of thiols for site
      specific functionalization, the construction of complex macromolecules and the
      generation of both biodegradable disulphides and non-biodegradable bonds which
      are the tools for constructing specific therapeutic/drug delivery systems. In
      addition, the ability of thiols to react with various functional groups found in
      a variety of polymer science materials and biological entities such as peptide
      and related structures will also be demonstrated. Despite of the fact that
      research efforts in thiol chemistry are still at the early stages, it is likely
      that its true potential will be developed. 

PMID- 25601063
TI  - Soft governance, restratification and the 2004 general medical services contract:
      the case of UK primary care organisations and general practice teams.
AB  - In the UK National Health Service, primary care organisation (PCO) managers have
      traditionally relied on the soft leadership of general practitioners based on
      professional self-regulation rather than direct managerial control. The 2004
      general medical services contract (nGMS) represented a significant break from
      this arrangement by introducing new performance management mechanisms for PCO
      managers to measure and improve general practice work. This article examines the
      impact of nGMS on the governance of UK general practice by PCO managers through a
      qualitative analysis of data from an empirical study in four UK PCOs and eight
      general practices, drawing on Hood's four-part governance framework. Two hybrids
      emerged: (i) PCO managers emphasised a hybrid of oversight, competition
      (comptrol) and peer-based mutuality by granting increased support, guidance and
      autonomy to compliant practices; and (ii) practices emphasised a broad acceptance
      of increased PCO oversight of clinical work that incorporated a restratified
      elite of general practice clinical peers at both PCO and practice levels. Given
      the increased international focus on the quality, safety and efficiency in
      primary care, a key issue for PCOs and practices will be to achieve an effective,
      contextually appropriate balance between the counterposing governance mechanisms
      of peer-led mutuality and externally led comptrol. 

PMID- 25601064
TI  - Understanding health through social practices: performance and materiality in
      everyday life.
AB  - The importance of recognising structure and agency in health research to move
      beyond methodological individualism is well documented. To progress incorporating
      social theory into health, researchers have used Giddens' and Bourdieu's
      conceptualisations of social practice to understand relationships between agency,
      structure and health. However, social practice theories have more to offer than
      has currently been capitalised upon. This article delves into contemporary
      theories of social practice as used in consumption and sustainability research to
      provide an alternative, and more contextualised means, of understanding and
      explaining human action in relation to health and wellbeing. Two key observations
      are made. Firstly, the latest formulations of social practice theory distinguish
      moments of practice performance from practices as persistent entities across time
      and space, allowing empirical application to explain practice histories and
      future trajectories. Secondly, they emphasise the materiality of everyday life,
      foregrounding things, technologies and other non-humans that cannot be ignored in
      a technologically dependent social world. In concluding, I argue the value of
      using contemporary social practice theories in health research is that they
      reframe the way in which health outcomes can be understood and could inform more
      effective interventions that move beyond attitudes, behaviour and choices.

PMID- 25601065
TI  - On interviewing people with pets: reflections from qualitative research on people
      with long-term conditions.
AB  - There is mounting evidence that pets are associated with physiological,
      psychological and social benefits for humans. Much of this research has come from
      western countries, where there have been consistent calls for greater engagement
      with pet ownership and health. Drawing on a secondary analysis of 61 in-depth
      interviews with people, or carers of people, with long-term conditions, we
      explore how pets feature in people's narrative accounts of their experiences. Our
      findings demonstrate the multifaceted nature of people's relationships with pets,
      and the embedded and embodied ways in which human-nonhuman interactions are
      played out in narratives of chronic illness. Our study differs from other work on
      pets and health in that, by returning to the interview video recordings, we were
      able to explore the sometimes three-way interactions, the co(a)gency, between
      participants, pets and researchers. Pets were often presented as important family
      members, yet the researchers' responses to the presence or talk about pets was
      often markedly different from their reactions to other household members. We
      conclude with cautioning against the downgrading of pets in narrative health
      research. Narrative approaches may invite participants to talk about what is
      important to them, yet they clearly have limitations in practice.

PMID- 25601066
TI  - Unstable terminality: negotiating the meaning of chronicity and terminality in
      motor neurone disease.
AB  - This paper explores the meaning of chronicity and terminality in motor neurone
      disease (MND), also known as amyotrophic lateral sclerosis (ALS). There is no
      known cause or cure for MND, and expected survival is 2-5 years, but several
      interventions may improve or prolong life. This study draws on qualitative
      interview data with health professionals in hospitals and primary care, and
      family carers, in Norway. The actors emphasised chronic and terminal aspects in
      subtly different ways along the entire illness trajectory, also when recounting
      the trajectory in retrospect. As a consequence of improved health services and
      medical technology the distinction between chronicity and terminality has become
      more vague and sometimes ambiguous. We suggest the concept unstable terminality
      to describe this ambiguity. While MND is a fatal diagnosis; it may be contested,
      as contingencies and interventions create an indefinite time scope. The
      instability creates challenges for primary care which is dependent on prognostic
      information to organise their effort; hospitals tackle the instability by pre
      scheduled consultations allowing for avoidance of an explicit prognosis. Some
      carers experienced what we understand as a disruption within the disruption,
      living with chronic and terminal illness simultaneously, which made the limbo
      phase more challenging to overcome.

PMID- 25601067
TI  - Male combat veterans' narratives of PTSD, masculinity, and health.
AB  - This article uniquely examines the ways a group of male combat veterans talk
      about masculinity and how, following post-traumatic stress disorder (PTSD), they
      performed masculinities in the context of a surfing group, and what effects this
      had upon their health and wellbeing. Participant observations and life history
      interviews were conducted with a group of combat veterans who belonged to a
      surfing charity for veterans experiencing PTSD. Data were rigorously explored via
      narrative analysis. Our findings revealed the ways in which veterans enacted
      masculinities in accordance with the values that were cultivated during military
      service. These masculine performances in the surfing group had important effects
      both on and for the veterans' wellbeing. Significantly, the study highlights how
      masculine performances can be seen alternately as a danger and as a resource for
      health and wellbeing in relation to PTSD. The article advances knowledge on
      combat veterans and mental health with critical implications for the promotion of
      male veterans' mental health. These include the original suggestion that health
      promoting masculine performances might be recognised and supported in PTSD
      treatment settings. Rather than automatically viewing masculinity as problematic,
      this article moves the field forward by highlighting how hegemonic masculinities
      can be reconstructed in positive ways which might improve veterans' health and
      wellbeing. A video abstract of this article can be found at:
      https://www.youtube.com/watch?v=BaYzaOP1kAY.

PMID- 25601068
TI  - The business of care: the moral labour of care workers.
AB  - Drawing on a case study conducted in a private residential care home, this
      article examines the emotional labour of care workers in relation to the moral
      construction of care and the practical experiences of work. An examination of the
      company's discursive attempts to construct, manage and demarcate its employees'
      emotional labour was carried out alongside an exploration of the carers' own
      interpretations of, and enrolment in, the care-giving role. The potential
      economic and emotional consequences of these occurrences were a key focus of the
      inquiry. The study found that carers, encouraged by the company, naturalised
      their emotional labour, and that this had contradictory consequences. On the one
      hand it justified the economic devaluation of the carer's work and left her
      vulnerable to emotional over-involvement and client aggression. On the other, it
      allowed the worker to defend the moral interests of those within her care and to
      see when those interests were in conflict with the economic motivations of her
      employer. 

PMID- 25601070
TI  - Patterns and causes of health inequalities in later life: a Bourdieusian
      approach.
AB  - This study explores the relationship between social class and health change in
      older people in a path analysis, using data from the English Longitudinal Study
      of Ageing (n = 6241) in a Bourdieusian theoretical framework. Bourdieu drew a
      distinction between the occupational characteristics by which people are
      classified and the secondary properties of class that relate to lifestyle
      (economic, cultural and social capitals). Our path model includes both
      occupational and secondary characteristics of objective social class as well as a
      measure of subjective social class. We investigate the effects of the predictors
      on change in three health outcomes (self-rated health, number of symptoms of
      depression and number of difficulties with the activities of daily living). The
      analysis adds to Bourdieusian research by showing how the effects of objective
      social class on health are partially mediated by perceived social status. It also
      adds to substantive research on the relationship between class and health by
      suggesting that class-related health inequalities do persist for older people,
      even for those who are not in paid employment. It suggests that a large amount of
      the effect of occupation on the health of older people is not direct but
      indirect; through their personal wealth and lifestyle. 

PMID- 25601069
TI  - Stopped hearts, amputated toes and NASA: contemporary legends among healthy
      volunteers in US phase I clinical trials.
AB  - The first stage of testing new pharmaceuticals in humans is referred to as a
      phase I clinical trial. The purpose of these studies is to test the safety of the
      drugs and to establish appropriate doses that can later be given to patients.
      Most of these studies are conducted under controlled, in-patient conditions using
      healthy volunteers who are paid for their participation. To explore healthy
      volunteers' experiences in clinical trials, an ethnographic study was conducted
      at six in-patient phase I clinics in the USA. In addition to the observation of
      clinic activities (from informed consent procedures to dosing to blood draws),
      268 semi-structured interviews were conducted, 33 with clinic staff and 235 with
      healthy volunteers. Drawing on this dataset, this article explores healthy
      volunteers' exchange of contemporary legends about phase I clinical trials. In
      addition to potentially scaring the listener and communicating distrust in the
      medical community, these incredible stories help participants cope with perceived
      stigma and establish a gradient of risk of trial participation, creating
      potential boundaries to their participation in medical research. The article
      argues that contemporary legends play a productive role in society, shaping how
      people view themselves and others and influencing their decisions about risky
      activities. 

PMID- 25601072
TI  - Complications following artificial urinary sphincter placement after radical
      prostatectomy and radiotherapy: a meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis of artificial urinary
      sphincter (AUS) placement after radical prostatectomy (RP) and external beam
      radiotherapy (EBRT). PATIENTS AND METHODS: There were 1 886 patients available
      for analysis of surgical revision outcomes and 949 for persistent urinary
      incontinence (UI) outcomes from 15 and 11 studies, respectively. The mean age
      (sd) was 66.9 (1.4) years and the number of patients per study was 126.6 (41.7).
      The mean (sd, range) follow-up was 36.7 (3.9, 18-68) months. A systematic
      database search was conducted using keywords, according to Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published
      series of AUS implantations were retrieved, according to the inclusion criteria.
      The Newcastle-Ottawa Score was used to ascertain the quality of evidence for each
      study. Surgical results from each case series were extracted. Data were analysed
      using CMA statistical software. RESULTS: AUS revision was higher in RP + EBRT vs
      RP alone, with a random effects risk ratio of 1.56 (95% confidence interval [CI]
      1.02-2.72; P < 0.050; I(2) = 82.0%) and a risk difference of 16.0% (95% CI 2.05
      36.01; P < 0.080). Infection/erosion contributed to the majority of surgical
      revision risk compared with urethral atrophy (P = 0.020). Persistent UI after
      implantation was greater in patients treated with EBRT (P < 0.001). CONCLUSIONS:
      Men receiving RP + EBRT appear at increased risk of infection/erosion and
      urethral atrophy, resulting in a greater risk of surgical revision compared with
      RP alone. Persistent UI is more common with RP + EBRT.

PMID- 25601073
TI  - Antigenic potential of a highly conserved Neisseria meningitidis
      lipopolysaccharide inner core structure defined by chemical synthesis.
AB  - Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We
      studied the potential of synthetic lipopolysaccharide (LPS) inner core structures
      as broadly protective antigens against N. meningitidis. Based on the specific
      reactivity of human serum antibodies to synthetic LPS cores, we selected a highly
      conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core
      tetrasaccharide induced a robust IgG response in mice when formulated as an
      immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection
      of N. meningitidis strains demonstrated the accessibility of the LPS core on
      viable bacteria. The distal trisaccharide was identified as the crucial epitope,
      whereas the proximal Kdo moiety was immunodominant and induced mainly
      nonprotective antibodies that are responsible for lack of functional protection
      in polyclonal serum. Our results identified key antigenic determinants of LPS
      core glycan and, hence, may aid the design of a broadly protective immunization
      against N. meningitidis.

PMID- 25601076
TI  - Flu epidemic rages across the USA.

PMID- 25601075
TI  - CDy6, a photostable probe for long-term real-time visualization of mitosis and
      proliferating cells.
AB  - Long-term real-time visualization of lysosomal dynamics has been challenging at
      the onset of mitosis due to the lack of fluorescent probes enabling convenient
      imaging of dividing cells. We developed a long-term real-time photostable mitotic
      or proliferating marker, CDy6, a BODIPY-derived compound of designation yellow 6,
      which labels lysosome. In long-term real-time, CDy6 displayed a sharp increase in
      intensity and change in localization in mitosis, improved photostability, and
      decreased toxicity compared with other widely used lysosomal and DNA markers, and
      the ability to label cells in mouse xenograft models. Therefore, CDy6 may open
      new possibilities to target and trace lysosomal contents during mitosis and to
      monitor cell proliferation, which can further our knowledge of the basic
      underlying biological mechanisms in the management of cancer. 

PMID- 25601074
TI  - Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual
      lasso Peptide from an understudied halophilic actinomycete.
AB  - Natural products are the most historically significant source of compounds for
      drug development. However, unacceptably high rates of compound rediscovery
      associated with large-scale screening of common microbial producers have resulted
      in the abandonment of many natural product drug discovery efforts, despite the
      increasing prevalence of clinically problematic antibiotic resistance. Screening
      of underexplored taxa represents one strategy to avoid rediscovery. Herein we
      report the discovery, isolation, and structural elucidation of streptomonomicin
      (STM), an antibiotic lasso peptide from Streptomonospora alba, and report the
      genome for its producing organism. STM-resistant clones of Bacillus anthracis
      harbor mutations to walR, the gene encoding a response regulator for the only
      known widely distributed and essential two-component signal transduction system
      in Firmicutes. To the best of our knowledge, Streptomonospora had been hitherto
      biosynthetically and genetically uncharacterized, with STM being the first
      reported compound from the genus. Our results demonstrate that understudied
      microbes remain fruitful reservoirs for the rapid discovery of novel, bioactive
      natural products. 

PMID- 25601077
TI  - New antibiotic discovered for Gram-positive bacteria.

PMID- 25601078
TI  - Smoking cessation efforts targeted at low-income smokers.

PMID- 25601079
TI  - Syria: the ongoing crisis.

PMID- 25601080
TI  - One in seven US adults has lung disease.

PMID- 25601081
TI  - Self-assembled nanoparticle micro-shells templated by liquid crystal sorting.
AB  - A current goal in nanotechnology focuses on the assembly of different
      nanoparticle types into 3D organized structures. In this paper we report the use
      of a liquid crystal host phase in a new process for the generation of micron
      scale vesicle-like nanoparticle shells stabilized by ligand-ligand interactions.
      The constructs formed consist of a robust, thin spherical layer, composed of
      closely packed quantum dots (QDs) and stabilized by local crystallization of the
      mesogenic ligands. Ligand structure can be tuned to vary QD packing within the
      shell and made UV cross-linkable to allow for intact shell extraction into
      toluene. The assembly method we describe could be extended to other nanoparticle
      types (metallic, magnetic etc.), where hollow shell formation is controlled by
      thermally sorting mesogen-functionalized nanoparticles in a liquid crystalline
      host material at the isotropic to nematic transition. This process represents a
      versatile method for making non-planar 3D nano-assemblies. 

PMID- 25601082
TI  - Category generalization in a new context: the role of visual attention.
AB  - Infants and children have difficulty categorizing objects in new contexts.
      However, learning in both same and varied contexts can help young word learners
      overcome contextual learning difficulties. We examined the relation between
      infants' visual attention to the category member and background context during
      learning and their ability to generalize a new category member in a new context.
      Of particular interest is how this relation is affected by learning in various
      contextual conditions. Infants (16-20 months; n=48) were presented with eight
      novel noun categories in one of three contextual conditions (same context, varied
      context, or a combination of same and varied contexts), and tested for their
      generalization ability in a new context. Context was defined as the colored and
      patterned fabric upon which the object was presented. Results suggest that visual
      attention during learning is associated with category generalization ability in a
      new context only for infants whose learning took place in a combination of same
      and varied background contexts. The results are discussed in terms of the
      mechanisms by which context affects generalization. 

PMID- 25601083
TI  - A novel link between Fic (filamentation induced by cAMP)-mediated
      adenylylation/AMPylation and the unfolded protein response.
AB  - The maintenance of endoplasmic reticulum (ER) homeostasis is a critical aspect of
      determining cell fate and requires a properly functioning unfolded protein
      response (UPR). We have discovered a previously unknown role of a post
      translational modification termed adenylylation/AMPylation in regulating signal
      transduction events during UPR induction. A family of enzymes, defined by the
      presence of a Fic (filamentation induced by cAMP) domain, catalyzes this
      adenylylation reaction. The human genome encodes a single Fic protein, called
      HYPE (Huntingtin yeast interacting protein E), with adenylyltransferase activity
      but unknown physiological target(s). Here, we demonstrate that HYPE localizes to
      the lumen of the endoplasmic reticulum via its hydrophobic N terminus and
      adenylylates the ER molecular chaperone, BiP, at Ser-365 and Thr-366. BiP
      functions as a sentinel for protein misfolding and maintains ER homeostasis. We
      found that adenylylation enhances BiP's ATPase activity, which is required for
      refolding misfolded proteins while coping with ER stress. Accordingly, HYPE
      expression levels increase upon stress. Furthermore, siRNA-mediated knockdown of
      HYPE prevents the induction of an unfolded protein response. Thus, we identify
      HYPE as a new UPR regulator and provide the first functional data for Fic
      mediated adenylylation in mammalian signaling. 

PMID- 25601085
TI  - Outcome of the management of open ankle fractures in an ortho-plastic specialist
      centre.
AB  - INTRODUCTION: We reviewed the functional outcome of 68 patients with open ankle
      fractures managed in an orthoplastic specialist centre. MATERIALS AND METHODS:
      Patients managed at Frenchay Hospital over a 6 year period were divided into 3
      groups: group P were patients initially seen and managed at Frenchay Hospital (an
      orthoplastic specialist centre), group S were patients stabilised at a different
      unit and referred for definitive management, while group R were patients managed
      in a different unit and referred following complications. Injuries were graded
      using the AO score and outcome was measured using the Enneking score (both
      validated). RESULTS: 19 patients (group P, mean age: 43 years), 26 patients
      (group S, mean age: 41 years) and 23 patients (group R, mean age: 41.9 years)
      made the cohort. 82.4% patients required free tissue transfer. Mean AO scores of
      groups P, S and R were 11.5, 12.3 and 9.7 (p+0.03). Mean number of procedures for
      P, S and R were 2.6, 3.5 and 4.2 (p = 0.0006). Mean follow up time was 55.5, 61.0
      and 57.0 weeks respectively (p = 0.72). Mean Enneking scores for groups P, S and
      R were 63.3, 74.8 and 73.5 (p = 0.16). CONCLUSION: Patients from groups S and R
      underwent more procedures. However, a similar outcome can be achieved,
      highlighting the importance of managing such injuries in an orthoplastic
      specialist centre.

PMID- 25601084
TI  - Structural basis of plant homeodomain finger 6 (PHF6) recognition by the
      retinoblastoma binding protein 4 (RBBP4) component of the nucleosome remodeling
      and deacetylase (NuRD) complex.
AB  - The NuRD complex is a conserved transcriptional coregulator that contains both
      chromatin-remodeling and histone deacetylase activities. Mutations of PHF6 are
      found in patients with Borjeson-Forssman-Lehmann syndrome, T-cell acute
      lymphoblastic leukemia, or acute myeloid leukemia. Recently, PHF6 was identified
      to interact with the NuRD complex, and this interaction is mediated by the RBBP4
      component. However, little is known about the molecular basis for the
      interaction. Here, we present the crystal structure of the complex of the NuRD
      subunit RBBP4 bound to the PHF6 peptide (residues 162-170). The PHF6 peptide
      binds to the top surface of the RBBP4 beta-propeller. A pair of positively
      charged residues of the PHF6 peptide insert into the negatively charged pocket of
      RBBP4, which is critical for the interaction between PHF6 and RBBP4.
      Corresponding PHF6 mutants impair this interaction in vitro and in vivo.
      Structural comparison shows that the PHF6-binding pocket overlaps with FOG1 and
      histone H3 on RBBP4/Nurf55, but it is distinct from the pocket recognizing
      histone H4, Su(z)12, and MTA1. We further show that the middle disordered region
      (residues 145-207, containing the RBBP4-binding motif) is sufficient for the
      transcriptional repression mediated by PHF6 on the GAL4 reporter, and knockdown
      of RBBP4 diminished the PHF6-mediated repression. Our RBBP4-PHF6 complex
      structure provides insights into the molecular basis of PHF6-NuRD complex
      interaction and implicates a role for PHF6 in chromatin structure modulation and
      gene regulation. 

PMID- 25601086
TI  - Late implant sepsis after fracture surgery in HIV positive patients.
AB  - A prospective cohort study was undertaken to assess the incidence of late-implant
      sepsis after internal fixation in HIV-positive patients. A total of 91 HIV
      positive patients (67 males and 24 females) who underwent 103 procedures (111
      implants) were followed up for a mean period of 27 months (range 12-66 months).
      No occurrences of late implant sepsis were found in 100 implants (94 procedures)
      in 82 patients at 27 months' follow-up (range 12-66 months). Nine patients (9
      procedures, 9 implants) developed early infections within 6 weeks and were
      treated with antibiotics (6 patients), amputation (1 patient) or removal of metal
      work (2 patients). There was no evidence of subsequent late implant sepsis in any
      of these patients, at a mean follow-up of 25 months (range 12-52 months). This
      study demonstrates that it is safe to perform internal fixation in HIV-positive
      patients, with no observed increase risk of late implant sepsis. There is no
      indication to remove implants after fracture union, other than for the general
      clinical indications that may lead to removal of metal work in any patient. 

PMID- 25601087
TI  - Three new flavans in dragon's blood from Daemonorops draco.
AB  - Three new flavans were isolated from chloroform extracts of dragon's blood from
      Daemonorops draco, together with eight known compounds. The structures of the new
      flavans were determined by 1D and 2D NMR spectroscopic analysis. These compounds
      are the first examples of 2-methoxyflavans from D. draco and regarded as
      derivatives of biogenetic intermediates from flavans to chalcones, which are
      characteristic of the dragon's blood. 

PMID- 25601088
TI  - The neuroscience of musical improvisation.
AB  - Researchers have recently begun to examine the neural basis of musical
      improvisation, one of the most complex forms of creative behavior. The emerging
      field of improvisation neuroscience has implications not only for the study of
      artistic expertise, but also for understanding the neural underpinnings of domain
      general processes such as motor control and language production. This review
      synthesizes functional magnetic resonance imagining (fMRI) studies of musical
      improvisation, including vocal and instrumental improvisation, with samples of
      jazz pianists, classical musicians, freestyle rap artists, and non-musicians. A
      network of prefrontal brain regions commonly linked to improvisatory behavior is
      highlighted, including the pre-supplementary motor area, medial prefrontal
      cortex, inferior frontal gyrus, dorsolateral prefrontal cortex, and dorsal
      premotor cortex. Activation of premotor and lateral prefrontal regions suggests
      that a seemingly unconstrained behavior may actually benefit from motor planning
      and cognitive control. Yet activation of cortical midline regions points to a
      role of spontaneous cognition characteristic of the default network. Together,
      such results may reflect cooperation between large-scale brain networks
      associated with cognitive control and spontaneous thought. The improvisation
      literature is integrated with Pressing's theoretical model, and discussed within
      the broader context of research on the brain basis of creative cognition. 

PMID- 25601089
TI  - Topical steroid-induced tinea pseudoimbricata: a striking form of tinea
      incognito.

PMID- 25601090
TI  - The role of hydrophobic alkyl chains in the physicochemical properties of
      poly(beta-amino ester)/DNA complexes.
AB  - Two degradable poly(beta-amino ester)s with an average molecular weight of 2kDa,
      referred to as B1 and B2, have been synthesized to be tested as non-viral gene
      delivery systems. B2 polymer exhibits two additional non-polar ethyl groups at
      both ends. This paper describes the influence of that subtle difference on the
      compaction ability and temporal stability of the complexes formed with plasmid
      DNA. Our results suggest that the inclusion of those small hydrophobic fragments
      into the polycation backbone improves its suitability as synthetic DNA carrier.
      The improvement is related to the formation and physicochemical properties of the
      complexes. B2 polyplexes were more stable, the polymer hydrolysis was slowed down
      and plasmid DNA was better protected which was translated into better
      transfection efficiencies. Although still not totally understood, the role played
      by hydrophobic forces is ubiquitous in chemical, biological and physical systems,
      and they must be considered to design future polymers for gene delivery. 

PMID- 25601091
TI  - One-step synthesized immunostimulatory oligonucleotides-functionalized quantum
      dots for simultaneous enhanced immunogenicity and cell imaging.
AB  - Unmethylated cytosine-phosphate-guanine (CpG) dinucleotides, normally occur in
      natural bacterial and viral genomes, show strong immunostimulatory activities to
      invading pathogens and have found widespread applications in both basic research
      and clinical trials. For the first time, we design a simple one-step synthesis of
      CpG-functionalized quantum dots (QDs), combining fascinating features of enhanced
      immunogenicity and cell imaging. The induction of QDs can greatly increase CpG
      uptake ability by TLR9-positive cells and elevate CpG stability against nuclease
      degradation. What is more, the outstanding optical properties also suggest that
      the CpG-QDs can serve as promising optical probes for the evaluation of the
      cellular uptake efficiency of the CpG motifs. To our best knowledge, this is the
      first report to use a facile one-pot synthesis strategy that allows the CpG
      functionalized QDs to be prepared, which are able to serve as both the potent
      platform for immunotherapy and the fluorescent probes for intracellular imaging. 

PMID- 25601092
TI  - Tailored polymer-lipid hybrid nanoparticles for the delivery of drug conjugate:
      dual strategy for brain targeting.
AB  - The object of the present study was to investigate the glioma targeting
      propensity of folic acid (F) decorated polymer-lipid hybrid nanoparticles (PLNs)
      encapsulating cyclo-[Arg-Gly-Asp-D-Phe-Lys] (cRGDfK) modified paclitaxel (PtxR
      FPLNs). The prepared PLNs were supposed to bypass the blood-brain barrier (BBB)
      efficiently and subsequently target integrin rich glioma cells. The developed
      formulations were characterized for size, shape, drug entrapment efficiency, and
      in vitro release profile. PtxR-FPLNs demonstrated highest in vitro inhibitory
      effect, cell apoptosis and cell uptake. Pharmacokinetics and biodistribution
      studies showed efficacy of PtxR-FPLNs in vivo. In vivo anti-tumor studies clearly
      revealed that the median survival time for Balb/C mice treated with PtxR-FPLNs
      (42 days) was extended significantly as compared to PtxR-PLNs (35 days), free
      PtxR (18 days), Ptx-FPLNs (38 days), Ptx-PLNs (30 days), free Ptx (14 days) and
      control group (12 days). From the results it can be concluded that the developed
      dual targeted nanoformulation was able to efficiently cross the BBB and
      significantly deliver higher amounts of drug to brain tumor for better
      therapeutic outcome.

PMID- 25601093
TI  - Gold nanoparticles coated zinc oxide nanorods as the matrix for enhanced L
      lactate sensing.
AB  - In this study, an enzymatic electrochemical biosensor for L-lactate detection was
      proposed. The device was developed based on gold nanoparticles (Au NPs) modified
      zinc oxide nanorods (ZnO NRs). The sensing performance of the device was examined
      by cyclic voltammetry and amperometry. Compared with pristine ZnO based
      biosensor, Au/ZnO based sensor exhibited higher sensitivity of 24.56 MUA cm(-2)
      mM(-1), smaller K(M)(app) of 1.58 mM, lower detection limit of 6 MUM and wider
      linear range of 10 MUM-0.6 mM for L-lactate detection. The introduction of Au NPs
      enhances electro-catalytic ability and electron migration, which contributes to
      the improvement of the sensing performance. Hence, the results confirm the
      essential character of Au NPs in such semiconductor based electrochemical
      biosensing system.

PMID- 25601094
TI  - 5-Fluorouracil delivery from metal-ion mediated molecularly imprinted cryogel
      discs.
AB  - The objective of this study is to prepare imprinted cryogel discs for delivery of
      5-fluorouracil. The coordinate bond interactions are utilized to accomplish a
      coordination complex between metal-chelate monomer N-methacryloyl-L-histidine and
      5-FU with the assistance of Cu(2+) ion. The complex is copolymerized with
      hydroxyethyl methacrylate to produce poly(hydroxyethyl methacrylate-N
      methacryloyl-(L)-histidine methyl ester) cryogel discs. The cryogel discs are
      characterized thoroughly by performing swelling tests, scanning electron
      microscopy, differential scanning calorimetry and X-ray diffraction studies. In
      vitro delivery studies are performed to investigate the effects of cross-linker
      ratio, medium pH and drug concentration. 5-FU imprinted cryogel discs have highly
      macroporous structures. Drug molecules are homogeneously dispersed in the 5-FU
      imprinted cryogel matrix. The cumulative release of 5-FU decreased by increasing
      the cross-linker density in the polymer matrix. Delivery rate of 5-FU varied with
      different pH values in a coordination complex since metal ion acts as a Lewis
      acid, and the ligand, i.e. 5-FU acts as a Lewis base. The cumulative release of 5
      FU increased with increasing drug concentration in polymer matrix. The nature of
      the 5-FU transport mechanism is non-Fickian.

PMID- 25601095
TI  - Construction of pH-sensitive lysozyme/pectin nanogel for tumor methotrexate
      delivery.
AB  - Novel nano-particles were developed from lysozyme-pectin through self-assembly,
      and the nanogels could be used as a carrier for the antitumor agent, methotrexate
      (MTX). The nanogels exhibited spherical with diameters about 109 +/- 2 nm and
      narrow particle size distribution, as well as negative surface charge.
      Furthermore, the particle size and morphology of the nanogels hardly changed with
      the incorporation of MTX. The loading capacity of MTX in nanogels could reach
      17.58 +/- 0.85%. MTX-loaded nanogels were pH-dependent, accelerated release of
      MTX at a decreasing pH from 7.4 to 5.3. The MTT assay indicated that encapsulated
      MTX exhibited higher anticancer activity than free MTX. Meanwhile, MTX-loaded
      nanogels could be effectively endocytosed by HepG2 cells, resulting in enhanced
      cancer-cell apoptosis comparing to free MTX. It indicated that the nanogels had
      good biocompatibility and low toxicity. The obtained nanogels had great potential
      in the development of a new nanocarrier for anti-cancer drug delivery.

PMID- 25601096
TI  - Effect of organic-ligands on the toxicity profiles of CdS nanoparticles and
      functional properties.
AB  - CdS nanoparticles are one among the most promising agents for fluorescent
      imaging. Hence, it is essential to develop new strategies to overcome the
      cytotoxicity of these nanoparticles. Surface modification is one of the simplest
      and effective techniques. This paper assesses the effect of surface modification
      on toxicity of the CdS nanoparticles. Unmodified CdS and surface-modified CdS
      nanoparticles were synthesized in an aqueous medium using a wet chemical route at
      room temperature. The surface modification of the CdS nanoparticles with
      polyvinylpyrrolidone (PVP) and cysteine was confirmed using infrared absorption
      studies. The diameters of unmodified CdS, PVP-modified CdS, and cysteine-modified
      CdS nanoparticles were determined using HRTEM. They exhibited luminescence in the
      range from 500 to 800 nm. The cytotoxic effects of these CdS nanoparticles were
      investigated in cultures of Vero cells. The results indicated that Vero cell
      viability was higher for the surface-modified CdS nanoparticles than for the
      unmodified CdS nanoparticles. The reduction in the toxicity was related to the
      nature of the capping agents used for the surface modification, and the particle
      size.

PMID- 25601097
TI  - Novel anti-infective implant substrates: controlled release of antibiofilm
      compounds from mesoporous silica-containing macroporous titanium.
AB  - Bone implants with open porosity enable fast osseointegration, but also present
      an increased risk of biofilm-associated infections. We design a novel implant
      material consisting of a mesoporous SiO2 diffusion barrier (pore diameter: 6.4
      nm) with controlled drug release functionality integrated in a macroporous Ti
      load-bearing structure (fully interconnected open porosity: 30%; pore window
      size: 0.5-2.0 MUm). Using an in vitro tool consisting of Ti/SiO2 disks in an
      insert set-up, through which molecules can diffuse from feed side to release
      side, a continuous release without initial burst effect of the antibiofilm
      compound toremifene is sustained for at least 9 days, while release
      concentrations (up to 17 MUM daily) increase with feed concentrations (up to
      4mM). Toremifene diffusivity through the SiO2 phase into H2O is estimated around
      10(-13)m(2)/s, suggesting configurational diffusion through mesopores. Candida
      albicans biofilm growth on the toremifene-release side is significantly
      inhibited, establishing a proof-of-concept for the drug delivery functionality of
      mesoporous SiO2 incorporated into a high-strength macroporous Ti carrier. Next
      generation implants made of this composite material and equipped with an internal
      reservoir (feed side) can yield long-term controlled release of antibiofilm
      compounds, effectively treating infections on the implant surface (release side)
      over a prolonged time.

PMID- 25601098
TI  - How does current diabetes care compare with landmark clinical studies?

PMID- 25601099
TI  - Selection and Socialization Effects in Early Adolescent Alcohol Use: A Propensity
      Score Analysis.
AB  - The robust correlation between peer and adolescent alcohol use (AU) has been
      taken as evidence for both socialization and selection processes in the etiology
      of adolescent AU. Accumulating evidence from studies using a diverse range of
      methodological and statistical approaches suggests that both processes are
      involved. A major challenge in testing whether peer AU predicts an adolescent's
      drinking (socialization) or whether an adolescent's drinking predicts peer AU
      (selection) is the myriad of potentially confounding factors that might lead to
      an overestimation of socialization and selection effects. After creating AU
      transition groups based on peer and adolescent AU across two waves (N = 765; age
      = 10-15; 53% female), we test whether transitions into AU by adolescents and
      peers predict later peer and adolescent AU respectively, using (1) propensity
      score analysis to balance transition groups on 26 potential confounds, (2) a
      longitudinal design with three waves to establish temporal precedence, and (3)
      both adolescent (target) and peer self-report of peer AU to disentangle effects
      attributable to shared reporter bias. Both selection and socialization were
      supported using both peer self-report of AU and adolescent-report of peer AU.
      Although cross-sectional analyses suggested peer self-reported models were
      associated with smaller effects than perceived peer AU, longitudinal analyses
      suggest a similar sized effect across reporter of peer AU for both selection and
      socialization. The implications of these findings for the etiology and treatment
      of adolescent AU are discussed.

PMID- 25601100
TI  - Partial dosage compensation in Strepsiptera, a sister group of beetles.
AB  - Sex chromosomes have evolved independently in many different taxa, and so have
      mechanisms to compensate for expression differences on sex chromosomes in males
      and females. Different clades have evolved vastly different ways to achieve
      dosage compensation, including hypertranscription of the single X in male
      Drosophila, downregulation of both X's in XX Caenorhabditis, or inactivation of
      one X in female mammals. In the flour beetle Tribolium, the X appears
      hyperexpressed in both sexes, which might represent the first of two steps to
      evolve dosage compensation along the paths mammals may have taken (i.e.,
      upregulation of X in both sexes, followed by inactivation of one X in females).
      Here we test for dosage compensation in Strepsiptera, a sister taxon to beetles.
      We identify sex-linked chromosomes in Xenos vesparum based on genomic analysis of
      males and females, and show that its sex chromosome consists of two chromosomal
      arms in Tribolium: The X chromosome that is shared between Tribolium and
      Strepsiptera, and another chromosome that is autosomal in Tribolium and another
      distantly related Strepsiptera species, but sex-linked in X. vesparum. We use RNA
      seq (RNA sequencing) to show that dosage compensation along the X of X. vesparum
      is partial and heterogeneous. In particular, genes that are X-linked in both
      beetles and Strepsiptera appear fully dosage compensated probably through
      downregulation in both sexes, whereas genes on the more recently added X segment
      have evolved only partial dosage compensation. In addition, reanalysis of
      published RNA-seq data suggests that Tribolium has evolved dosage compensation,
      without hypertranscribing the X in females. Our results demonstrate that patterns
      of dosage compensation are highly variable across sex-determination systems and
      even within species.

PMID- 25601101
TI  - Genome rearrangements can make and break small RNA genes.
AB  - Small RNAs (sRNAs) are short, transcribed regulatory elements that are typically
      encoded in the intergenic regions (IGRs) of bacterial genomes. Several sRNAs,
      first recognized in Escherichia coli, are conserved among enteric bacteria, but
      because of the regulatory roles of sRNAs, differences in sRNA repertoires might
      be responsible for features that differentiate closely related species. We
      scanned the E. coli MG1655 and Salmonella enterica Typhimurium genomes for
      nonsyntenic IGRs as a potential source of uncharacterized, species-specific sRNAs
      and found that genome rearrangements have reconfigured several IGRs causing the
      disruption and formation of sRNAs. Within an IGR that is present in E. coli but
      was disrupted in Salmonella by a translocation event is an sRNA that is
      associated with the FNR/CRP global regulators and influences E. coli biofilm
      formation. A Salmonella-specific sRNA evolved de novo through point mutations
      that generated a sigma(70) promoter sequence in an IGR that arose through genome
      rearrangement events. The differences in the sRNA pools among bacterial species
      have previously been ascribed to duplication, deletion, or horizontal
      acquisition. Here, we show that genomic rearrangements also contribute to this
      process by either disrupting sRNA-containing IGRs or creating IGRs in which novel
      sRNAs may evolve.

PMID- 25601103
TI  - Clinical and immunological evidence that low doses of pentavalent antimonials are
      effective in maintaining long-term cure of Leishmania (Viannia) braziliensis
      cutaneous lesions.

PMID- 25601102
TI  - Eumetazoan cryptochrome phylogeny and evolution.
AB  - Cryptochromes (Crys) are light sensing receptors that are present in all
      eukaryotes. They mainly absorb light in the UV/blue spectrum. The extant Crys
      consist of two subfamilies, which are descendants of photolyases but are now
      involved in the regulation of circadian rhythms. So far, knowledge about the
      evolution, phylogeny, and expression of cry genes is still scarce. The inclusion
      of cry sequences from a wide range of bilaterian species allowed us to analyze
      their phylogeny in detail, identifying six major Cry subgroups. Selective gene
      inactivations and stabilizations in multiple chordate as well as arthropod
      lineages suggest several sub- and/or neofunctionalization events. An expression
      study performed in zebrafish, the model organism harboring the largest amount of
      crys, showed indeed only partially overlapping expression of paralogous mRNA,
      supporting gene sub- and/or neofunctionalization. Moreover, the daily cry
      expression in the adult zebrafish retina indicated varying oscillation patterns
      in different cell types. Our extensive phylogenetic analysis provides for the
      first time an overview of cry evolutionary history. Although several, especially
      parasitic or blind species, have lost all cry genes, crustaceans have retained up
      to three crys, teleosts possess up to seven, and tetrapods up to four crys. The
      broad and cyclic expression pattern of all cry transcripts in zebrafish retinal
      layers implies an involvement in retinal circadian processes and supports the
      hypothesis of several autonomous circadian clocks present in the vertebrate
      retina. 

PMID- 25601104
TI  - Cyborg beast: a low-cost 3d-printed prosthetic hand for children with upper-limb
      differences.
AB  - BACKGROUND: There is an increasing number of children with traumatic and
      congenital hand amputations or reductions. Children's prosthetic needs are
      complex due to their small size, constant growth, and psychosocial development.
      Families' financial resources play a crucial role in the prescription of
      prostheses for their children, especially when private insurance and public
      funding are insufficient. Electric-powered (i.e., myoelectric) and body-powered
      (i.e., mechanical) devices have been developed to accommodate children's needs,
      but the cost of maintenance and replacement represents an obstacle for many
      families. Due to the complexity and high cost of these prosthetic hands, they are
      not accessible to children from low-income, uninsured families or to children
      from developing countries. Advancements in computer-aided design (CAD) programs,
      additive manufacturing, and image editing software offer the possibility of
      designing, printing, and fitting prosthetic hands devices at a distance and at
      very low cost. The purpose of this preliminary investigation was to describe a
      low-cost three-dimensional (3D)-printed prosthetic hand for children with upper
      limb reductions and to propose a prosthesis fitting methodology that can be
      performed at a distance. RESULTS: No significant mean differences were found
      between the anthropometric and range of motion measurements taken directly from
      the upper limbs of subjects versus those extracted from photographs. The Bland
      and Altman plots show no major bias and narrow limits of agreements for lengths
      and widths and small bias and wider limits of agreements for the range of motion
      measurements. The main finding of the survey was that our prosthetic device may
      have a significant potential to positively impact quality of life and daily
      usage, and can be incorporated in several activities at home and in school.
      CONCLUSIONS: This investigation describes a low-cost 3D-printed prosthetic hand
      for children and proposes a distance fitting procedure. The Cyborg Beast
      prosthetic hand and the proposed distance-fitting procedures may represent a
      possible low-cost alternative for children in developing countries and those who
      have limited access to health care providers. Further studies should examine the
      functionality, validity, durability, benefits, and rejection rate of this type of
      low-cost 3D-printed prosthetic device.

PMID- 25601105
TI  - Formation of a built-in field at the porphyrin/ITO interface directly proven by
      the time-resolved photovoltage technique.
AB  - Two assemblies, porphyrin powder/ITO and porphyrin film/ITO, were built by a
      facile method. The time-resolved photovoltage technique was utilized to prove the
      behaviour of photo-induced charges in the two assemblies. The photovoltage
      results show that the porphyrin film/ITO assembly displays a reversal polarity
      response, which is different from the response of porphyrin powder/ITO. This
      phenomenon is due to the effect of a built-in field on photo-induced charge
      behaviour at the porphyrin film/ITO interface. This result is beneficial for the
      development of a measuring method for detecting heterojunction interface
      formation and understanding the photoelectric process in photoelectric materials
      and devices. 

PMID- 25601107
TI  - [Sonothrombolysis for acute ischemic stroke].
AB  - BACKGROUND: Sonothrombolysis (ST) is an emerging modality for the treatment of
      stroke. AIM: To assess the feasibility to perform ST in a Chilean hospital.
      MATERIAL AND METHODS: Patients attended at a private clinic with an acute
      ischemic stroke, between September 2002 and May 2013 and eligible for endovenous
      thrombolysis, were studied with a transcranial Doppler (Spencer PMD 100 or
      150(r)). Those with an adequate sonographic window and a demonstrated arterial
      occlusion were monitored continuously with transcranial Doppler at the site of
      worst residual flow following the CLOTBUST study protocol. RESULTS: One thousand
      twenty six patients were studied, of whom 136 received intravenous thrombolysis
      (rt-PA) and 61, aged 66 +/- 18 years (59% males), were subjected to ST (7% of
      total). Their median National Institutes of Health Stroke Scale score was 14, the
      lapse from symptom onset to rt-PA was 127 minutes (43-223). Middle cerebral
      artery (MCA) occlusion was found in 88.5% of patients. Complete recanalization
      was achieved in 44.3% of patients. Sixty percent had Modified Rankin Scale of 0
      to 2 at 3 months (95% confidence intervals (CI) 48.1 to 72). Case fatality was
      9.8% and asymptomatic intracranial hemorrhage occurred in 9.8% (95% CI: 4.3 to
      20.2). CONCLUSIONS: ST can be carried out in a complex medical center and is
      safe.

PMID- 25601106
TI  - [Outcomes using two preservation solutions (UW/HTK) in liver transplantation from
      brain death donors].
AB  - BACKGROUND: Preservation solutions are critical for organ transplantation. In
      liver transplant (LT), the solution developed by the University Of Wisconsin (UW)
      is the gold-standard to perfuse deceased brain death donor (DBD) grafts.
      Histidine-Tryptophan-Ketoglutarate (HTK), formerly a cardioplegic infusion, has
      been also used in solid organ transplantation. AIM: To compare the outcomes of LT
      in our center using either HTK or UW solution. PATIENTS AND METHODS:
      Retrospective study including 93 LT DBD liver grafts in 89 patients transplanted
      between March 1994 and July 2010. Forty-eight grafts were preserved with UW and
      45 with HTK. Donor and recipient demographics, total infused volume, cold
      ischemia time, post-reperfusion biopsy, liver function tests, incidence of
      biliary complications, acute rejection and 12-month graft and patient survival
      were assessed. Preservation solution costs per liver graft were also recorded.
      RESULTS: Donor and recipient demographics were similar. When comparing UW and
      HTK, no differences were observed in cold ischemia time (9.6 +/- 3 and 8.7 +/- 2
      h respectively, p = 0.23), biliary complications, the incidence of acute
      rejection, primary or delayed graft dysfunction. Histology on post-reperfusion
      biopsies revealed no differences between groups. The infused volume was
      significantly higher with HTK than with UW (9 (5-16) and 6 (3-11) l, p < 0.001).
      The cost per procurement was remarkably lower using HTK. CONCLUSIONS: Perfusion
      of DBD liver grafts with HTK is clinically equivalent to UW, with a significant
      cost reduction.

PMID- 25601108
TI  - [Influence of psychosocial factors on adherence to antihypertensive drug therapy:
      results from a Cardiovascular Health Program cohort followed in the Metropolitan
      Region of Santiago, Chile].
AB  - BACKGROUND: Inadequate blood pressure control in hypertensive patients remains a
      persistent health problem in Chile and worldwide. Poor adherence to
      antihypertensive drug therapy is one of the frequently cited factors. OBJECTIVES:
      To determine the influence of psychosocial factors in the adherence to drug
      therapy in hypertensive patients followed through a Cardiovascular Health Program
      (CHP) that provides free access to primary care centers located in the
      Metropolitan Region of Santiago, Chile. METHODS: Cross sectional study. A
      randomized sample of 513 hypertensive patients (30 to 68 years) was obtained from
      a universe of 1.484 patients. Adherence to treatment was determined by the
      Morisky-Green-Levine test. Demographic, socioeconomic and average values of blood
      pressure were recorded. Validated questionnaires were utilized to assess the
      patient-physician relationship, awareness of being hypertensive, patient
      perception of social support, family cohesion, patient self-health assessment and
      symptoms of emotional stress and depression. RESULTS: The drug therapy adherence
      was 36.6%, higher in women (38.4% vs 28.9%; p < 0.001). After multivariate
      analysis, absence of adherence was associated with male gender (OR: 1.76 [95% CI
      1.21-2.56]), low education (OR: 1.72 [95% CI 1.18 to 2.53]), inadequate patient
      physician relationship (OR: 1.56 [95% CI 1.13 to 2.27]), and high level of
      emotional stress and depression (OR: 1.93 [95% CI 1.27 to 2.94]). CONCLUSIONS:
      Our study highlights the influence of inadequate patient-physician relation, high
      level of emotional stress and depression, low education level and income and male
      gender in the lack of adherence to antihypertensive drug therapy in hypertensive
      patients followed throughout the CHP.

PMID- 25601109
TI  - [Eating disorders risk among obese adolescents].
AB  - BACKGROUND: Preliminary research suggests that eating disorders (ED) are common
      among overweight teenagers. Missing the diagnosis is a poor prognostic factor.
      AIM: To quantify the risk of ED and the effects of age, sex and severity of
      obesity in obese adolescents. PATIENTS AND METHODS: We studied 99 obese
      adolescents with a body mass index (BMI) > percentile 95 of CDC-NCHS, 51%
      females, aged between 11 and 19 years, attending an obesity clinic. The Eating
      Disorders Inventory-2 (EDI-2) was used to evaluate the risk of ED. A score equal
      or higher than 110, corresponding to the 85th percentile, was considered as
      risky. RESULTS: Sixteen percent of studied adolescents had EDI scores > 110. No
      statistically significant differences were observed by age, sex or severity of
      obesity. EDI-2 scores in participants with a BMI z score over and under 4 were
      93.6 +/- 33.9 and 78.2 +/- 38.8 respectively (p = 0.02). A high percentage of
      participants had body dissatisfaction (BD) and drive for thinness. Bulimic
      symptoms, inefficacy, fear of maturity, and impulsivity scores were significantly
      higher among participants with a high risk of developing ED. CONCLUSIONS: Obese
      adolescents have a high risk for ED, regardless of their age and sex. The risk
      increases along with higher BMI. The routine use of screening tests is
      fundamental for an early detection of ED.

PMID- 25601110
TI  - [Parental perceptions and expectations about sexual and reproductive health care
      for urban adolescents].
AB  - Studies have reported which expectations and demands adolescents have for more
      accessible sexual and reproductive health (SRH) services. However, there is
      limited information regarding parents' requirements and demands for SRH services
      their adolescents need. AIM: To explore the knowledge of parents regarding SRH
      needs of their adolescent daughters and sons and what they demand from primary
      health care services (PHCS). MATERIAL AND METHODS: A quali-quantitative,
      descriptive, cross-sectional study was performed. Nine fathers and 24 mothers
      were interviewed to design a survey. In the quantitative phase, 125 mothers
      voluntarily, anonymously and confidentially were interviewed. All participants
      were users of PHCS of urban communities in the Metropolitan Area showing a high
      percentage of births by adolescents' mothers. Data analysis was descriptive and
      analytical. RESULTS: Interviews served as input to design the questionnaire.
      Seventy seven percent (77,6%) of interviewed mothers knew that their
      sons/daughters, regardless of their gender, had concern about sexuality; their
      main fear was adolescent pregnancy. Seventy six percent (76%) was aware that
      their sons/daughters might request attention in SRH clinics and 97% agreed that
      they should require these services during early adolescence. The most desirable
      features of such services were identified. CONCLUSIONS: Parents recognize that
      they would prefer their sons/daughters postponed sexual initiation; however, they
      are aware that pregnancy prevention is needed. Mothers approve SRH services. They
      agree that counseling to prevent pregnancies and sexual transmitted diseases
      (STD) and AIDS was an important issue. They require support for themselves and
      their sons/daughters.

PMID- 25601111
TI  - [Treatment of diabetic ketoacidosis using 2009 American Diabetes Association
      guidelines].
AB  - BACKGROUND: During 2009, new guidelines for the treatment of diabetic
      ketoacidosis were published by the American Diabetes Association. AIM: To assess
      the impact of new treatment guidelines on the evolution of patients treated for
      diabetic ketoacidosis (KAD). PATIENTS AND METHODS: Anonymous data was obtained
      from computational medical records of patients treated for KAD at our institution
      two years before ("Traditional Protocol") and TWO years after ("ADA-2009
      Protocol") the publication of the 2009 American Diabetes Association (ADA) KAD
      guidelines. RESULTS: Twenty three patients aged 36.5 +/- 15.1 years were treated
      with the traditional method and 23 patients aged 44.4 +/- 21.1 years were treated
      following 2009 ADA guidelines. Among patients treated with the traditional
      protocol and treated following ADA 2009 guidelines, the diabetes type 1/type 2
      ratio was 18/5 and 19/16 respectively (p = NS), the glycosylated hemoglobin on
      admission was 12.6 +/- 2.5 and 14.3 +/- 2.7% respectively (p = 0.03), minimal
      blood pH was 7.15 +/- 0.14 and 7.19 +/- 0.09 respectively (p = NS), bicarbonate
      was required in seven and no patient respectively (p = 0.01), hypokalemia < 3.5
      mEq/L occurred in 78.2 and 48.5% of patients (p = 0.03), the lapse until
      resolution was 28.7 +/- 28.0 and 28.8 +/- 20.6 hours (p = NS). Only one patient,
      treated following ADA 2009 guidelines, died. CONCLUSIONS: Introduction of the ADA
      2009 protocol for the treatment of KAD resulted in decrease in the use of
      intravenous bicarbonate and a reduction in the incidence of hypokalemia. There
      was no impact neither in the lapse until resolution or lethality.

PMID- 25601113
TI  - [Recommendations of health care users and professionals to achieve a timely
      access to HIV diagnosis].
AB  - BACKGROUND: Early HIV (human immunodeficiency virus) diagnosis optimizes
      therapies aimed at reducing viral load, increasing survival, lowering health
      costs and reducing the number of people infected with the virus. In Chile,
      despite widespread and readily available HIV testing, infected people continue to
      get tested in a late fashion and are usually diagnosed in advanced stages of the
      disease. AIM: To determine the elements that facilitate or impede a timely HIV
      testing and to evaluate how to improve the access to HIV testing. MATERIAL AND
      METHODS: Descriptive, in-depth interviews to 30 participants with unknown
      serology, 15 participants diagnosed at AIDS stage and 15 health care
      professionals working at a primary healthcare settings. RESULTS: Users and
      professionals formulated three suggestions to improve timely access to ELISA test
      for HIV diagnosis. Namely, to inform users and professionals about the
      characteristics of the disease and diagnostic test, to offer fast and easy access
      to HIV testing, and to train the whole healthcare team about obtaining informed
      consent for testing. CONCLUSIONS: These recommendations should be implemented at
      healthcare centers to attain a timely HIV diagnosis.

PMID- 25601112
TI  - [Evaluation of the SF-12: usefulness of the mental health scale].
AB  - BACKGROUND: The SF-12 is one of the most used questionnaires to evaluate the
      multidimensional health related quality of life, worldwide. However, the factor
      structure does not match the structure of the original instrument. Besides, most
      studies centered in the physical dimension paying less attention to mental health
      related quality of life. AIM: To evaluate the psychometric properties of the SF
      12 and to validate the mental health dimension of this questionnaire. MATERIAL
      AND METHODS: Two studies were conducted, the first consisting of 840 people aged
      between 18 and 60 years, who answered the SF-12. In the second study, 970 people
      aged between 18 and 60 years answered the SF-12 questionnaire, the Beck
      Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI).
      Reliability (internal consistency and temporal stability) was analyzed, along
      with construct and criterion validity for the mental health dimension. RESULTS:
      The reliability estimate using Cronbach's alpha in both studies was higher than
      0.74 in both dimensions (physical and psychological). Construct validity analysis
      yielded a three factor complex solution. Finally the criterion validity analysis
      showed appropriate and significant correlations with depression and anxiety.
      CONCLUSIONS: The SF-12 and its mental health scale are suitable for
      epidemiological characterization studies.

PMID- 25601114
TI  - [A survey about client orientation and wayfinding in Chilean hospitals].
AB  - BACKGROUND: Sense of orientation in hospitals can be tricky considering the large
      extension of buildings and the inadequate signage. AIM: To report some of the
      findings of a larger research project on wayfinding and patient navigation in
      Chilean hospitals. MATERIAL AND METHODS: Five hundred nine hospital users waiting
      for attention in three hospitals were contacted and asked to answer a survey that
      lasted 10 minutes, about wayfinding and sense of orientation within the hospital.
      RESULTS: Users declared to have a good opinion of existing signage in the three
      hospitals analyzed as well as their architectural organization in terms of their
      capacity to orient people. However, the vast majority of users asked for
      directions to navigate within the hospital to staff and medical personnel.
      CONCLUSIONS: Patient navigation problems are imposing a great "hidden" cost to
      hospitals management due to missed appointments.

PMID- 25601115
TI  - [A new proposal for the diagnosis of depression].
AB  - Depression has a high impact on mental health. However its diagnosis is a
      challenge even for specialists. This problem derives from a failure in an
      adequate description and differentiation of the disease. This inadequate
      conceptualization generates these difficulties. Our thesis is that depression
      should be understood as a complex phenomenon that can be analyzed from multiple
      perspectives, from genes to behavior, including personality and interaction with
      the sociocultural environment. The aim of this paper is to review the
      psychopathological construct of depression from a multidimensional point of view,
      considering clinical, sociocultural, characterological and pathogenic variables.
      Finally we provide a proposal for an adequate diagnostic approach. 

PMID- 25601116
TI  - [Breaking bad news in clinical practice].
AB  - Breaking bad news is a complex task that requires multiple communication skills
      from health professionals. Clinical practice demands to communicate all type of
      bad news, from a diagnosis of cancer to adverse effects of a treatment. On the
      other hand, since the beginning of the health reform in 2003, the need to improve
      the quality of services was proposed, among which the concern about the rights
      and duties of patients stands out. Therefore, the health care provider-patient
      relationship becomes again the subject of discussion and study, and a topic of
      great importance for clinical work. We revise the consequences of breaking bad
      news for the patient and for the health care provider, as well as the current
      protocols available for this purpose. The importance of developing communication
      skills both for future health professionals as for those who currently work in
      the area is emphasized. 

PMID- 25601117
TI  - [Positive psychosocial factors and cardiovascular health].
AB  - Health is defined as a state of complete physical, mental and social wellbeing
      and not merely as the absence of disease. Thus, medical practice must not only
      deal with diagnosis and treatment of pathological conditions and solve physical
      ailments, but also promote a comprehensive wellbeing state -including the
      psychological domain- to achieve positive health. Therefore, it is necessary to
      scientifically identify the psychological and social determinants that contribute
      more effectively to prevent disease and achieve optimal health. This article
      reviews the most recent evidence showing the importance of positive psychological
      and social resources on cardiovascular disease, the leading cause of morbidity
      and mortality as well as health care costs worldwide. Evidence is summarized
      regarding the role of positive psychosocial factors as health promoters and
      protectors against cardiovascular risk, the possible mechanisms that explain this
      association, and the practical implications and future research arising from this
      perspective. The development of interdisciplinary research in this field,
      incorporating the area of psychological wellbeing, should help to generate and
      test new strategies aimed at more effective cardiovascular disease prevention and
      treatment. 

PMID- 25601118
TI  - [The virtuous doctor in cinema: the final examination].
AB  - The virtuous doctor has subscribed an oath and by subscribing to this solemn
      promise, he is committed to live in accordance with the purposes, obligations and
      virtues established in the medical profession. Cinematic art has shown only a
      superficial interest in complex aspects of medical profession. An exception is
      Ingmar Bergman's film "Wild Strawberries", where Professor Isak Borg, a widowed
      76-year-old physician, is to be awarded the Doctor Jubilaris degree, 50 years
      after he received his doctorate at Lund University. During the trip, Isak is
      forced by a nightmare to reevaluate his professional life as not being a virtuous
      doctor.

PMID- 25601119
TI  - [Resistant human fasciolasis: report of four patients].
AB  - Human fascioliasis is a parasitic zoonosis that affects the liver of human and
      herbivorous animals. In chronic cases, its diagnosis is confirmed by direct
      visualization of parasitic eggs in stool examination, by positive testing for
      Fasciola hepatica antigens in stools, or by direct observation of parasites by
      endoscopic retrograde cholangiography or surgery. In acute cases, serological
      reactions as immunoblothing or detection of parasite antigens in the blood are
      useful. The treatment of choice is triclabendazole. However, parasite resistance
      in animals, as well as in man, has been reported to this drug. We report four
      patients in whom the parasitic infection persisted despite a course of treatment
      with triclabendazole.

PMID- 25601120
TI  - [Hemolysis, serositis and exanthema induced by Mycoplasma pneumoniae infection.
      Report of one case].
AB  - Mycoplasma infections have extrapulmonary manifestations that may be associated
      with respiratory symptoms and may have skin, heart, gastrointestinal,
      rheumatologic, neurologic, hematologic involvement. Cold agglutinin mediated
      autoimmune hemolytic anemia is the most common hematological manifestation. We
      report a 27-year-old woman infected with Mycoplasma pneumoniae, who presented
      respiratory involvement with pneumonia, exanthema, serositis and acute hemolytic
      anemia that required transfusion. The key for the diagnosis were the
      extrapulmonary manifestations associated with respiratory involvement after five
      days of hospitalization. 

PMID- 25601121
TI  - [Armand Trousseau (1801-1867), his history and the signs of hypocalcemia].
AB  - Armand Trousseau (1801-1867) was born in Tours, France on October 14, 1801. He
      graduated as a physician in the same city under the direction of Pierre
      Bretonneau and received his doctorate in 1825 in Paris. He was the first
      physician to practice tracheotomy in diphtheria and perform thoracenteses to
      remove air or fluid from the pleural space. He recommended tracheal intubation in
      different scenarios. He described the first cases of laryngeal tuberculosis and
      the presence of carpopedal spasm in hypocalcemia, a sign that has his name. He
      also described the association between migratory thrombophlebitis and neoplasia,
      which is known as Trousseau's syndrome. Ironically, on January 1, 1867 he
      diagnosed in himself a deep vein thrombosis of the left upper limb and told one
      of his disciples "I am lost; I have no doubt about the nature of my disease". He
      died of gastric cancer at the age of 66 years on June 23, 1867. He carried out an
      educational and medical work. He instructed his students about the rather
      instantaneous thought process in clinical medicine. He always conducted his
      clinical work with the certainty of a sound scientific background. Contemporary
      physicians should take advantage of the example and lessons of Armand Trousseau. 

PMID- 25601123
TI  - [Specifying the "environmental effect on the incidence of Hantavirus
      cardiopulmonary syndrome in Chile"].

PMID- 25601124
TI  - [IgG4 related disease: extrapancreatic manifestations in autoinmune
      pancreatitis].

PMID- 25601125
TI  - [First subregional meeting of health sciences students' scientific journal
      editors, Arequipa, Peru, 2014].

PMID- 25601126
TI  - [XXXV Chilean congress of Internal Medicine].

PMID- 25601127
TI  - Number of embryos biopsied as a predictive indicator for the outcome of
      preimplantation genetic diagnosis by fluorescence in situ hybridisation in
      translocation cases.
AB  - This study aimed to investigate the optimum number of embryos to be biopsied in
      order to increase the likelihood of obtaining a balanced/normal embryo following
      preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridisation
      (FISH) for translocation carriers. Patients with low number of fertilised oocytes
      (<=5) or low number of embryos available for PGD (<7) underwent multiple hormonal
      stimulation cycles and their embryos from each cycle were vitrified and
      accumulated to obtain at least three embryos for PGD. Fifty-seven PGD cycles were
      performed for translocation carriers by FISH on day 3 of embryo development. PGD
      and pregnancy outcomes were examined according to the number of embryos biopsied.
      The cancellation rates of embryo transfer for the reciprocal translocation
      carriers were 40% when more than eight embryos were biopsied and it was as high
      as 78% when low number of embryos (less than nine) were biopsied. For
      Robertsonian translocation carriers, when more than eight embryos were biopsied,
      there were no embryo transfer cancellations. This study showed that when there
      are more than nine embryos biopsied for PGD, the likelihood of obtaining a
      balanced embryo and positive pregnancy outcome is significantly higher (P < 0.05)
      in such the overall pregnancy rate was 63% for reciprocal and 86% for
      Robertsonian carriers. This was reduced to only 7% for reciprocal and 14% for
      Robertsonian translocation carriers when less than nine embryos were biopsied.
      One of the limitations of this study was that the analysis was performed by FISH
      and more studies should investigate the outcomes of embryo accumulation following
      comprehensive chromosome analysis. 

PMID- 25601128
TI  - Rasagiline for the treatment of parkinsonism in Huntington's disease.

PMID- 25601129
TI  - Feedforward somatosensory inhibition is normal in cervical dystonia.
AB  - BACKGROUND: Insufficient cortical inhibition is a key pathophysiological finding
      in dystonia. Subliminal sensory stimuli were reported to transiently inhibit
      somatosensory processing. Here we investigated whether such subliminal
      feedforward inhibition is reduced in patients with cervical dystonia. METHODS:
      Sixteen cervical dystonia patients and 16 matched healthy controls performed a
      somatosensory detection task. We measured the drop in sensitivity to detect a
      threshold-level digital nerve shock when it was preceded by a subliminal
      conditioning shock, compared to when it was not. RESULTS: Subliminal conditioning
      shocks reduced sensitivity to threshold stimuli to a similar extent in both
      patients and controls, suggesting that somatosensory subliminal feedforward
      inhibition is normal in cervical dystonia. CONCLUSION: Somatosensory feedforward
      inhibition was normal in this group of cervical dystonia patients. Our results
      qualify previous concepts of a general dystonic deficit in sensorimotor
      inhibitory processing.

PMID- 25601130
TI  - A novel homozygous PLA2G6 mutation causes dystonia-parkinsonism.

PMID- 25601131
TI  - Three-dimensionally bonded spongy graphene material with super compressive
      elasticity and near-zero Poisson's ratio.
AB  - It is a challenge to fabricate graphene bulk materials with properties arising
      from the nature of individual graphene sheets, and which assemble into monolithic
      three-dimensional structures. Here we report the scalable self-assembly of
      randomly oriented graphene sheets into additive-free, essentially homogenous
      graphene sponge materials that provide a combination of both cork-like and rubber
      like properties. These graphene sponges, with densities similar to air, display
      Poisson's ratios in all directions that are near-zero and largely strain
      independent during reversible compression to giant strains. And at the same time,
      they function as enthalpic rubbers, which can recover up to 98% compression in
      air and 90% in liquids, and operate between -196 and 900  degrees C. Furthermore,
      these sponges provide reversible liquid absorption for hundreds of cycles and
      then discharge it within seconds, while still providing an effective near-zero
      Poisson's ratio. 

PMID- 25601132
TI  - Orexin A expression in the ovary of dog and cat.
AB  - Orexin A and B, also known as hypocretin A and B, are hypothalamic neuropeptides
      arising from a precursor to the 130 amino acid, called pre-pro orexin. They are
      synthesized mainly in lateral and posterior hypothalamus and are involved in
      different functions such as regulation of food intake and energy balance. Orexins
      and orexin receptors were previously described also in different tissues and
      organs outside the brain. The aim of this study was to demonstrate by means of
      the immunofluorescence technique, the presence of orexin A in the ovary of cat
      and dog, to support the hypothesis of the role of this substance also at the
      level of the female genital system. The presence of orexin A in the ovary either
      in dog or in cat is in agreement with previous data on the presence and role of
      orexins in the female genital system of other species. 

PMID- 25601133
TI  - CT perfusion imaging in response assessment of pulmonary metastases undergoing
      stereotactic ablative radiotherapy.
AB  - INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is an emerging
      treatment technique for pulmonary metastases in which conventional Response
      Evaluation Criteria in Solid Tumours (RECIST) may be inadequate. This study aims
      to assess the utility of CT perfusion imaging in response assessment of pulmonary
      metastases after SABR. METHODS: In this ethics board-approved prospective study,
      11 patients underwent a 26-Gy single fraction of SABR to pulmonary metastases. CT
      perfusion imaging occurred prior to and at 14 and 70 days post-SABR. Blood flow
      (mL/100 mL/min), blood volume (mL/100 mL), time to peak (seconds) and surface
      permeability (mL/100 mL/min), perfusion parameters of pulmonary metastases
      undergoing SABR, were independently assessed by two radiologists. Inter-observer
      variability was analysed. CT perfusion results were analysed for early response
      assessment comparing day 14 with baseline scans and for late response by
      comparing day 70 with baseline scans. The largest diameter of the pulmonary
      metastases undergoing SABR was recorded. RESULTS: Ten patients completed all
      three scans and one patient had baseline and early response assessment CT
      perfusion scans only. There was strong level of inter-observer agreement of CT
      perfusion interpretation with a median intraclass coefficient of 0.87 (range 0.20
      0.98). Changes in all four perfusion parameters and tumour sizes were not
      statistically significant. CONCLUSION: CT perfusion imaging of pulmonary
      metastases is a highly reproducible imaging technique that may provide additional
      response assessment information above that of conventional RECIST, and it
      warrants further study in a larger cohort of patients undergoing SABR.

PMID- 25601134
TI  - The relationship of periaortic fat thickness and cardiovascular risk factors in
      children with Turner syndrome.
AB  - Children with Turner syndrome (TS) have a broad range of later health problems,
      including an increased risk of cardiovascular morbidity and mortality. The aim of
      this study was to evaluate the relationship between periaortic fat thickness
      (PAFT) and metabolic and cardiovascular profiles in children with TS. Twenty-nine
      TS and 29 healthy children and adolescents were enrolled in the study.
      Anthropometric measurements, pubertal staging, and blood pressure measurements
      were performed. Fasting serum glucose, insulin, and lipid profile were measured.
      Periaortic fat thickness was measured using an echocardiography method, which has
      not previously been applied in children with TS. No difference was found between
      TS and control subject (CS) in age, weight, waist/hip ratio, HDL cholesterol and
      LDL cholesterol levels. However, in TS subjects, total cholesterol (p = 0.045)
      was greater than that in controls. It was determined that 13.7 % (N: 4) of TS
      subjects had dyslipidemia. Mean fasting glucose, fasting insulin, QUICK-I, HOMA,
      and FGIR index were similar in TS and in CS, whereas 17.2 % (N: 5) of TS subjects
      had insulin resistance (IR) and 13.7 % (N: 4) had impaired glucose tolerance. Six
      subjects (20.6 %) were diagnosed as hypertensive. Periaortic fat thickness was
      significantly higher in the TS group (p < 0.001) (0.1694 +/- 0.025 mm in the TS
      group and 0.1416 +/- 0.014 mm in the CS group) In children with TS, PAFT was
      positively correlated with fasting insulin, body mass index, and diastolic blood
      pressure. Our results provide additional evidence for the presence of subclinical
      cardiovascular disease in TS. In addition to existing methods, we recommend the
      measurement of periaortic fat thickness in children with TS to reveal the
      presence of early atherosclerosis.

PMID- 25601135
TI  - White matter injury and the inflammatory response following neonatal cardiac
      surgery.
AB  - White matter injury (WMI) is a known complication following neonatal heart
      surgery in term infants. In preterm infants, WMI has been associated with the
      degree of systemic inflammation. It is not known whether inflammation is an
      important mechanism of WMI as documented by magnetic resonance imaging (MRI)
      following neonatal heart surgery with cardiopulmonary bypass. Term neonates with
      congenital heart disease were enrolled in a prospective study with postoperative
      MRI. White matter injury was recorded by the number of T1 hyperintense foci with
      >5 foci consistent with significant WMI. Eleven candidate cytokine markers (INF
      gamma, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL
      13) were assayed preoperatively and daily for 5 days following surgery. Multiple
      clinical factors were recorded and correlated with WMI. Ninety-two subjects were
      enrolled in the study. The median age at surgery was 5 days (interquartile range
      4-7 days). Compared with the presurgery level, there were statistically
      significant increases (p < 0.005) for 8 out of 11 inflammatory markers. In all,
      64 postoperative MRIs were performed. No significant correlation was detected
      between WMI and clinical variables or inflammatory markers assessed immediately
      postoperative and on postoperative days 1 and 3, with exception of IL-1 beta on
      postoperative day 1. WMI correlates poorly with the systemic inflammatory
      response after congenital heart surgery and a number of herein measured clinical
      factors. WMI following neonatal heart surgery is a complex, still incompletely
      understood phenomenon that warrants continued investigation.

PMID- 25601137
TI  - Next generation phenotyping using the unified medical language system.
AB  - BACKGROUND: Structured information within patient medical records represents a
      largely untapped treasure trove of research data. In the United States, privacy
      issues notwithstanding, this has recently become more accessible thanks to the
      increasing adoption of electronic health records (EHR) and health care data
      standards fueled by the Meaningful Use legislation. The other side of the coin is
      that it is now becoming increasingly more difficult to navigate the profusion of
      many disparate clinical terminology standards, which often span millions of
      concepts. OBJECTIVE: The objective of our study was to develop a methodology for
      integrating large amounts of structured clinical information that is both
      terminology agnostic and able to capture heterogeneous clinical phenotypes
      including problems, procedures, medications, and clinical results (such as
      laboratory tests and clinical observations). In this context, we define
      phenotyping as the extraction of all clinically relevant features contained in
      the EHR. METHODS: The scope of the project was framed by the Common Meaningful
      Use (MU) Dataset terminology standards; the Systematized Nomenclature of Medicine
      Clinical Terms (SNOMED CT), RxNorm, the Logical Observation Identifiers Names and
      Codes (LOINC), the Current Procedural Terminology (CPT), the Health care Common
      Procedure Coding System (HCPCS), the International Classification of Diseases
      Ninth Revision Clinical Modification (ICD-9-CM), and the International
      Classification of Diseases Tenth Revision Clinical Modification (ICD-10-CM). The
      Unified Medical Language System (UMLS) was used as a mapping layer among the MU
      ontologies. An extract, load, and transform approach separated original
      annotations in the EHR from the mapping process and allowed for continuous
      updates as the terminologies were updated. Additionally, we integrated all
      terminologies into a single UMLS derived ontology and further optimized it to
      make the relatively large concept graph manageable. RESULTS: The initial
      evaluation was performed with simulated data from the Clinical Avatars project
      using 100,000 virtual patients undergoing a 90 day, genotype guided, warfarin
      dosing protocol. This dataset was annotated with standard MU terminologies,
      loaded, and transformed using the UMLS. We have deployed this methodology to
      scale in our in-house analytics platform using structured EHR data for 7931
      patients (12 million clinical observations) treated at the Froedtert Hospital. A
      demonstration limited to Clinical Avatars data is available on the Internet using
      the credentials user "jmirdemo" and password "jmirdemo". CONCLUSIONS: Despite its
      inherent complexity, the UMLS can serve as an effective interface terminology for
      many of the clinical data standards currently used in the health care domain.

PMID- 25601138
TI  - Pd-nanoparticle-supported, PDDA-functionalized graphene as a promising catalyst
      for alcohol oxidation.
AB  - Poly(diallyldimethylammonium chloride) (PDDA) has been employed as a modifying
      material for the development of new functional materials; then, the
      functionalized graphene was employed as a support for Pd nanoparticles through a
      facile method. The structures and morphologies of the as-synthesized Pd/PDDA
      graphene composites were extensively characterized by Raman spectroscopy, XRD,
      XPS, and TEM. Morphological observation showed that Pd NPs with average diameters
      of 4.4 nm were evenly deposited over the functionalized graphene sheets.
      Moreover, the electrochemical experiments indicated that the Pd/PDDA-graphene
      catalyst showed improved electrocatalytic activity toward alcohol-oxidation
      reactions compared to the Pd/graphene and commercial Pd/C systems, as well as
      previously reported Pd-based catalysts. This study demonstrates the great
      potential of PDDA-functionalized graphene as a support for the development of
      metal-graphene nanocomposites for important applications in fuel cells. 

PMID- 25601139
TI  - Chemical, radiochemical and biological studies of new gallium(III) complexes with
      hexadentate chelators.
AB  - New N4O2-donor acyclic chelators 2-[[2-[2-(3,5-dimethylpyrazol-1-yl)ethyl-[2-[(2
      hydroxyphenyl)methylamino]ethyl]amino]ethylamino]methyl]phenol (H2L(pz*,NH)) and
      2-[[2-[2-[(2-hydroxyphenyl)methylamino]ethyl-(2
      pyridylmethyl)amino]ethylamino]methyl]phenol (H2L(py,NH)) were obtained upon
      introduction of pyridyl or pyrazolyl coordinating units at the central nitrogen
      atom of diethylenetriamine (dien) and by functionalization of its terminal amines
      with phenol groups. The coordination behavior of H2L(pz*,NH) and H2L(py,NH) was
      evaluated towards (nat)Ga/(67)Ga, aiming to assess their suitability to obtain
      Ga(iii) chelates relevant for biomedical applications. Single crystal X-ray
      diffraction analysis of the complexes [GaL(pz*,NH)](ClO4) and [GaL(py,NH)](ClO4)
      confirmed the presence of N4O2-hexadentate chelators with the phenoxide groups
      coordinated cis relatively to the pyridyl/pyrazolyl arms. Unlike
      [GaL(pz*,NH)](ClO4), [GaL(py,NH)](ClO4) exists in solution as a mixture of
      isomers, as confirmed by several NMR techniques. The corresponding radiocomplex
      [(67)GaL(py,NH)](+) was obtained smoothly in almost quantitative radiochemical
      yield, contrary to [(67)GaL(pz*,NH)](+) that seems to be (hemi)labile under the
      same conditions. [(67)GaL(py,NH)](+) presents a high in vivo stability and a
      favourable biodistribution profile in mice. The imine congeners 2-[(E)-2-[2-(3,5
      dimethylpyrazol-1-yl)ethyl-[2-[(E)-(2
      hydroxyphenyl)methyleneamino]ethyl]amino]ethyliminomethyl]phenol
      (H2L(pz*,C[double bond, length as m-dash]N)) and 2-[(E)-2-[2-[(E)-(2
      hydroxyphenyl)methyleneamino]ethyl-(2-pyridylmethyl)amino]ethyliminomethyl]phenol
      (H2L(py,C[double bond, length as m-dash]N)) were also evaluated but they did not
      form complexes compatible for biomedical applications owing to their high
      reactivity. 

PMID- 25601140
TI  - Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells
      and mononuclear cells and the impact of the administration route in an intact
      porcine model.
AB  - BACKGROUND AIMS: Bone marrow mononuclear cells (BM-MNCs) and bone marrow-derived
      mesenchymal stem stromal cells (BM-MSCs) could have therapeutic potential for
      numerous conditions, including ischemia-related injury. Cells transplanted
      intravascularly may become entrapped in the lungs, which potentially decreases
      their therapeutic effect and increases the risk for embolism. METHODS: Twelve
      pigs were divided into groups of 3 and received (99m)Tc- hydroxymethyl-propylene
      amine-oxime-labeled autologous BM-MNCs or allogeneic BM-MSCs by either
      intravenous (IV) or intra-arterial (IA) transplantation. A whole body scan and
      single photon emission computed tomography/computed tomography (SPECT/CT) were
      performed 8 h later, and tissue biopsies were collected for gamma counting. A
      helical CT scan was also performed on 4 pigs to detect possible pulmonary
      embolism, 2 after IV BM-MSC injection and 2 after saline injection. RESULTS: The
      transplantation route had a greater impact on the biodistribution of the BM-MSCs
      than the BM-MNCs. The BM-MNCs accumulated in the spleen and bones, irrespective
      of the administration route. The BM-MSCs had relatively higher uptake in the
      kidneys. The IA transplantation decreased the deposition of BM-MSCs in the lungs
      and increased uptake in other organs, especially in the liver. Lung atelectases
      were frequent due to mechanical ventilation and attracted transplanted cells. CT
      did not reveal any pulmonary embolism. CONCLUSIONS: Both administration routes
      were found to be safe, but iatrogenic atelectasis might be an issue when cells
      accumulate in the lungs. The IA administration is effective in avoiding pulmonary
      entrapment of BM-MSCs. The cell type and administration method both have a major
      impact on the acute homing.

PMID- 25601141
TI  - Residues that influence coenzyme preference in the aldehyde dehydrogenases.
AB  - To find out the residues that influence the coenzyme preference of aldehyde
      dehydrogenases (ALDHs), we reviewed, analyzed and correlated data from their
      known crystal structures and amino-acid sequences with their published kinetic
      parameters for NAD(P)(+). We found that the conformation of the Rossmann-fold
      loops participating in binding the adenosine ribose is very conserved among
      ALDHs, so that coenzyme specificity is mainly determined by the nature of the
      residue at position 195 (human ALDH2 numbering). Enzymes with glutamate or
      proline at 195 prefer NAD(+) because the side-chains of these residues
      electrostatically and/or sterically repel the 2'-phosphate group of NADP(+). But
      contrary to the conformational rigidity of proline, the conformational
      flexibility of glutamate may allow NADP(+)-binding in some enzymes by moving the
      carboxyl group away from the 2'-phosphate group, which is possible if a small
      neutral residue is located at position 224, and favored if the residue at
      position 53 interacts with Glu195 in a NADP(+)-compatible conformation. Of the
      residues found at position 195, only glutamate interacts with the NAD(+)
      adenosine ribose; glutamine and histidine cannot since their side-chain points
      are opposite to the ribose, probably because the absence of the electrostatic
      attraction by the conserved nearby Lys192, or its electrostatic repulsion,
      respectively. The shorter side-chains of other residues-aspartate, serine,
      threonine, alanine, valine, leucine, or isoleucine-are distant from the ribose
      but leave room for binding the 2'-phosphate group. Generally, enzymes having a
      residue different from Glu bind NAD(+) with less affinity, but they can also bind
      NADP(+) even sometimes with higher affinity than NAD(+), as do enzymes containing
      Thr/Ser/Gln195. Coenzyme preference is a variable feature within many ALDH
      families, consistent with being mainly dependent on a single residue that
      apparently has no other structural or functional roles, and therefore can easily
      be changed through evolution and selected in response to physiological needs. 

PMID- 25601142
TI  - Short look-back periods in pharmacoepidemiologic studies of new users of
      antibiotics and asthma medications introduce severe misclassification.
AB  - PURPOSE: The aim of this study was to quantify the effect of the look back period
      on the misclassification of new users of antibiotics and asthma medications.
      METHODS: We included all children born in Denmark from 1995 through 2006 and all
      prescriptions of antibiotics and asthma medication from 1995 through 2011. The
      study period was 2007 through 2011. True new users redeemed their first
      prescription in the study period whereas prior users redeemed their first
      prescription before the study period. Look-back periods ranged from 30 days up to
      12 years prior to the study period, and we defined new users as those without a
      prescription in the look-back period. The relative misclassification (RM) was
      estimated as the number of defined new users divided by the number of true new
      users. RESULTS: For antibiotics, the RM decreased from 4.75 for look-back periods
      of 30 days to 2.36 for 2 years and 1.33 for 5 years. For asthma medication, the
      RM decreased from 2.53 for look-back periods of 30 days to 1.48 for 2 years and
      1.20 for 5 years. Older age, male gender, and absence of treatment-related
      diagnoses were associated with higher RM. CONCLUSIONS: Studies applying the new
      user design are strongly dependent on the available information on prescriptions.
      For drug classes with intermittent use such as asthma medications, even a 2-year
      look-back period produced severe misclassification. Excluding children with a
      prior treatment-related diagnosis can reduce the level of misclassification.

PMID- 25601143
TI  - Prolonged second stage of labour, maternal infectious disease, urinary retention
      and other complications in the early postpartum period.
AB  - OBJECTIVE: To study the association between duration of second stage of labour
      and risks of maternal complications (infection, urinary retention, haematoma or
      ruptured sutures) in the early postpartum period. DESIGN: Population-based cohort
      study. SETTING AND SAMPLE: We included 72 593 mothers with singleton vaginal
      deliveries at >=37 weeks of gestation in cephalic presentation, using the
      obstetric database from the Stockholm-Gotland region in Sweden, 2008-12. METHODS:
      Logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals
      (95% CI) were calculated and adjustments were made for maternal age, body mass
      index, height, smoking, cohabitation, gestational age, labour induction, epidural
      analgesia and oxytocin augmentation. RESULTS: Rates of any complication varied by
      parity from 7.3% in parous women with previous caesarean section, 4.8% in
      primiparas and 1.7% in parous women with no previous caesarean section. Compared
      with a second stage <1 hour, the adjusted ORs for any complication (95% CI) in
      primiparas were for 1 to <2 hours 1.28 (1.11-1.47); 2 to <3 hours 1.54 (1.32
      1.79), 3 to <4 hours 1.63 (1.38-1.93) and >=4 hours 2.08 (1.74-2.49). The
      corresponding adjusted ORs for parous women without previous caesarean were 2.27
      (1.78-2.90), 2.97 (2.09-4.22), 3.65 (2.25-5.94) and 3.16 (1.44-6.94),
      respectively. The adjusted ORs for women with previous caesarean were for 1 to <2
      hours 1.62 (1.13-2.32); 2 to <3 hours 1.56 (1.00-2.43), 3 to <4 hours 2.42 (1.52
      3.87), and >=4 hours 2.31 (1.25-4.24). CONCLUSIONS: Risks of maternal
      complications in the postpartum period increase with duration of second stage of
      labour also after accounting for maternal, pregnancy and delivery
      characteristics. Special attention has to be given to parous women with previous
      caesarean deliveries.

PMID- 25601144
TI  - Living with chronic neuropathic pain after spinal cord injury: an interpretative
      phenomenological analysis of community experience.
AB  - PURPOSE: This article presents an in-depth, idiographic study examining the lived
      experience of chronic pain following spinal cord injury (SCI). Neuropathic pain
      (NP) occurs in a large majority of the SCI population and is particularly
      intractable to treatment. It can be both psychologically and physically
      debilitating. This study examines how the experience of NP is mediated by its
      meaning to the sufferer. METHODS: Semi-structured interviews were conducted with
      eight people with SCI and chronic NP, attending outpatient clinics at a
      specialist SCI Centre in the UK. Verbatim transcripts were subjected to
      interpretative phenomenological analysis to further understand the experience.
      RESULTS: Analysis suggested that NP has powerful consequences upon the sufferer's
      physical, psychological and social well-being, in line with a biopsychosocial
      understanding of pain. Three super-ordinate themes were identified: a perceived
      gap between treatments received and participants' views of what they wanted and
      needed; a fight for life control and acceptance; and feeling understood by others
      with SCI, but isolated from the non-understanding able-bodied. CONCLUSIONS: The
      results are discussed in terms of the possible application of acceptance-based
      therapy to NP and the potential for the alleviation of the debilitating
      consequences of NP. IMPLICATIONS FOR REHABILITATION: Chronic NP after SCI is
      often described as worse than the injury itself, often impacting upon the
      sufferers physical and psychological health. The experiences of persons with SCI
      specific NP highlight the impact of pain on their physical, psychological and
      social health. This indicates that healthcare professionals should incorporate a
      biopsychosocial approach for managing pain post-SCI. Routine clinical follow-up
      of SCI patients with chronic NP, as well as comprehensive pain management
      treatment programmes, could address the three themes evidenced in the current
      study, by moving routine intervention with NP away from pain relief, towards pain
      management. Continued education for patients, friends, family members and
      healthcare professionals may be beneficial in promoting understanding and
      awareness of NP and its consequences following SCI.

PMID- 25601145
TI  - Biological control of Rigidoporus lignosus in Hevea brasiliensis in Nigeria.
AB  - The study was conducted to evaluate in vitro and in vivo control of fungal
      antagonists on Rigidoporus lignosus (klotzsch) Imaz in Hevea brasiliensis (Willd.
      ex A. Juss.) Muell. Arg. in the rain forest zone of Nigeria. In vitro assessments
      of biological agents were carried out in dixenic cultures in Petri plates. In
      vivo tests were carried out in the nursery using Hypocrea virens and Hypocrea
      jecorina. Significant differences were observed with the dual inoculations of
      fungal antagonists and R. lignosus inoculated the same day, and the antagonists
      inoculated 24 h before inoculation of R. lignosus. Hypocrea jecorina was most
      effective in the control of R. lignosus with percentage inhibition of 86.83 %.
      Hypocrea virens, H. jecorina, Trichoderma spirale, Trichoderma sp., Trichoderma
      sp. Pers, and Hypocrea lixii were effective on R. lignosus. Fungal antagonists
      inoculated 24 h before inoculation of R. lignosus exhibited higher inhibitory
      efficacies than antagonists and R. lignosus inoculated the same day. In the in
      vivo evaluation of fungi antagonists on R. lignosus, seedlings in H. jecorina
      treatment at 60 d and H. virens treatment at 150 d after inoculations
      respectively had the highest plant heaths (highest length of stem and length of
      tap rot, lowest plant death, and least foliar symptom) compared to the control.
      Mortality rate was higher at 60 d after inoculation and decline from the third
      months onward. Significant differences were observed between the control and R.
      lignosus treatment in all the parameters evaluated.

PMID- 25601146
TI  - Delimitation of cryptic species inside Claviceps purpurea.
AB  - Claviceps purpurea is an ovarian parasite infecting grasses (Poaceae) including
      cereals and forage plants. This fungus produces toxic alkaloids and consumption
      of contaminated grains can cause ergotism in humans and other mammals. Recent
      molecular genetics studies have indicated that it included three cryptic species
      (G1, G2, G3). In this study, reproductive isolation amongst these groups and
      among material from Phragmites and Molinia was tested using gene flow statistics
      for five polymorphic loci, and to support these data, phylogenetic affiliations
      based on gene trees and a multigene phylogeny were used. The four recognized
      species are characterized based on morphology and host spectrum and formal
      taxonomic names are proposed. Claviceps purpurea sensu stricto (G1 group)
      represents a typical rye ergot, but infects various other grasses. Typical hosts
      of Claviceps humidiphila (new name for G2 species), like Phalaris arundinacea,
      belong to grasses preferring humid locations. Claviceps spartinae (G3) is
      specific to chloridoid grasses from salt barches. The material from Phragmites
      and Molinia can be authenticated with the species Claviceps microcephala for
      which the new name Claviceps arundinis is proposed here. The divergence time
      between species was estimated and the tools for species identification are
      discussed. 

PMID- 25601148
TI  - New species of Ophiocordyceps unilateralis, an ubiquitous pathogen of ants from
      Thailand.
AB  - Ophiocordyceps unilateralis is an ubiquitous pathogen of ants with hidden
      phylogenetic diversity associated with host specificity. In this study, we
      describe two new species to this species complex: Ophiocordyceps septa and
      Ophiocordyceps rami. Both were found on unidentified ants of the genus Camponotus
      (C. sp.1 and C. sp2 respectively). Ophiocordyceps septa is very similar to
      Ophiocordyceps polyrhachis-furcata, Ophiocordyceps camponoti-leonardi, and
      Ophiocordyceps camponoti-saundersi (found respectively on the ants Polyrhachis
      furcata, Camponotus leonardi, and Camponotus saundersi) but differs in the size,
      the shape and the septation of the ascospores, while O. rami is clearly
      identifiable with macro-morphological features including multiple stromata
      similar to Ophiocordyceps halabalaensis on Camponotus gigas. A thorough
      morphological examination was also provided for O. polyrhachis-furcata, O.
      camponoti-leonardi, and O. camponoti saundersi, showing that the first was
      apparently distinguishable from the others by the absence of septation of the
      ascospores. A combined molecular phylogeny also supports O. septa and O. rami as
      distinct new species.

PMID- 25601147
TI  - Species composition of the genus Saprolegnia in fin fish aquaculture
      environments, as determined by nucleotide sequence analysis of the nuclear rDNA
      ITS regions.
AB  - The ITS region of the rDNA gene was compared for Saprolegnia spp. in order to
      improve our understanding of nucleotide sequence variability within and between
      species of this genus, determine species composition in Canadian fin fish
      aquaculture facilities, and to assess the utility of ITS sequence variability in
      genetic marker development. From a collection of more than 400 field isolates,
      ITS region nucleotide sequences were studied and it was determined that there was
      sufficient consistent inter-specific variation to support the designation of
      species identity based on ITS sequence data. This non-subjective approach to
      species identification does not rely upon transient morphological features.
      Phylogenetic analyses comparing our ITS sequences and species designations with
      data from previous studies generally supported the clade scheme of Dieguez
      Uribeondo et al. (2007) and found agreement with the molecular taxonomic cluster
      system of Sandoval-Sierra et al. (2014). Our Canadian ITS sequence collection
      will thus contribute to the public database and assist the clarification of
      Saprolegnia spp. taxonomy. The analysis of ITS region sequence variability
      facilitated genus- and species-level identification of unknown samples from
      aquaculture facilities and provided useful information on species composition. A
      unique ITS-RFLP for the identification of S. parasitica was also described. 

PMID- 25601149
TI  - Cadophora species associated with wood-decay of grapevine in North America.
AB  - Cadophora species are reported from grapevine (Vitis vinifera L.) in California,
      South Africa, Spain, Uruguay, and Canada. Frequent isolation from vines co
      infected with the Esca pathogens (Togninia minima and Phaeomoniella
      chlamydospora), and confirmation of its ability to cause wood
      lesions/discoloration in pathogenicity tests, suggest that C. luteo-olivacea is
      part of the trunk pathogen complex. In North America, little is known regarding
      the diversity, geographic distribution, and roles of Cadophora species as trunk
      pathogens. Accordingly, we characterized 37 Cadophora isolates from ten US states
      and two Canadian provinces, based on molecular and morphological comparisons, and
      pathogenicity. Phylogenetic analysis of three loci (ITS, translation elongation
      factor 1-alpha (TEF1-alpha) and beta-tubulin (BT)) distinguished two known
      species (C. luteo-olivacea and Cadophora melinii) and three newly-described
      species (Cadophora orientoamericana, Cadophora novi-eboraci, and Cadophora
      spadicis). C. orientoamericana, C. novi-eboraci, and C. spadicis were restricted
      to the northeastern US, whereas C. luteo-olivacea was only recovered from
      California. C. melinii was present in California and Ontario, Canada.
      Morphological characterization was less informative, due to significant overlap
      in dimensions of conidia, hyphae, conidiophores, and conidiogenous cells.
      Pathogenicity tests confirmed the presence of wood lesions after 24 m, suggesting
      that Cadophora species may have a role as grapevine trunk pathogens. 

PMID- 25601150
TI  - Effect of ultraviolet radiation A and B on growth and mycotoxin production by
      Aspergillus carbonarius and Aspergillus parasiticus in grape and pistachio media.
AB  - The effects of two exposure times per day (6 and 16 h) of UV-A or UV-B radiation,
      combined with dark and dark plus light incubation periods during 7-21 d on fungal
      growth and mycotoxins production of Aspergillus species were studied. Aspergillus
      carbonarius and Aspergillus parasiticus were inoculated on grape and pistachio
      media under diurnal and nocturnal temperatures choosing light photoperiod
      according to harvest conditions of these crops in Spain. Ultraviolet irradiation
      had a significant effect on A. carbonarius and A. parasiticus colony size
      (diameter, biomass dry weight, and colony density) and mycotoxin accumulation,
      although intraspecies differences were observed. Inhibition of A. carbonarius
      fungal growth decreased when exposure time was reduced from 16 h to 6 h, but this
      was not always true for ochratoxin A (OTA) production. OTA reduction was higher
      under UV-A than UV-B radiation and the reduction increased along time conversely
      to the aflatoxins (AFs). Aflatoxin B1 (AFB1) was the main toxin produced by A.
      parasiticus except in the UV-B light irradiated colonies which showed a higher
      percentage of AFG than AFB. Morphological changes were observed in colonies grown
      under UV-B light.

PMID- 25601151
TI  - Generally detected genes in comparative transcriptomics in bivalves: toward the
      identification of molecular markers of cellular stress response.
AB  - The specificity and representativeness of protein-coding genes identified by
      transcriptomics as biomarkers for environmental toxicological stress is crucial.
      We extracted the differential gene expression profile data from 49 published
      comparative transcriptomic studies of bivalves from January 2004 till November
      2014 performed in 15 different bivalve species. Among the studies, 77 protein
      coding genes were frequently detected when we use threefold of the average
      detection frequency as cut-off. Cellular organization and communication, protein
      and energy metabolism, stress response are the main functional classes of these
      proteins. We consider if these protein-coding genes represent common cellular
      stress responses of bivalves. 

PMID- 25601152
TI  - Major dietary patterns and risk of frailty in older adults: a prospective cohort
      study.
AB  - BACKGROUND: There is emerging evidence of the role of certain nutrients as risk
      factors for frailty. However, people eat food, rather than nutrients, and no
      previous study has examined the association between dietary patterns empirically
      derived from food consumption and the risk of frailty in older adults. METHODS:
      This is a prospective cohort study of 1,872 non-institutionalized individuals
      aged >=60 years recruited between 2008 and 2010. At baseline, food consumption
      was obtained with a validated diet history and, by using factor analysis, two
      dietary patterns were identified: a 'prudent' pattern, characterized by high
      intake of olive oil and vegetables, and a 'Westernized' pattern, with a high
      intake of refined bread, whole dairy products, and red and processed meat, as
      well as low consumption of fruit and vegetables. Participants were followed-up
      until 2012 to assess incident frailty, defined as at least three of the five
      Fried criteria (exhaustion, weakness, low physical activity, slow walking speed,
      and unintentional weight loss). RESULTS: Over a 3.5-year follow-up, 96 cases of
      incident frailty were ascertained. The multivariate odds ratios (95% confidence
      interval) of frailty among those in the first (lowest), second, and third tertile
      of adherence to the prudent dietary pattern were 1, 0.64 (0.37-1.12), and 0.40
      (0.2-0.81), respectively; P-trend = 0.009. The corresponding values for the
      Westernized pattern were 1, 1.53 (0.85-2.75), and 1.61 (0.85-3.03); P-trend =
      0.14. Moreover, a greater adherence to the Westernized pattern was associated
      with an increasing risk of slow walking speed and weight loss. CONCLUSIONS: In
      older adults, a prudent dietary pattern showed an inverse dose-response
      relationship with the risk of frailty while a Westernized pattern had a direct
      relationship with some of their components. Clinical trials should test whether a
      prudent pattern is effective in preventing or delaying frailty.

PMID- 25601153
TI  - Acute neuroinflammation in a clinically relevant focal cortical ischemic stroke
      model in rat: longitudinal positron emission tomography and immunofluorescent
      tracking.
AB  - Adequate estimation of neuroinflammatory processes following ischemic stroke is
      essential for better understanding of disease mechanisms, and for the development
      of treatment strategies. With the TSPO (18 kDa translocator protein) positron
      emission tomography (PET) radioligand [(11)C]PBR28, we monitored longitudinally
      the inflammatory response post-transient cerebral ischemia in rats, using a
      recently developed rat stroke model that produces isolated focal cortical
      infarcts with clinical relevance in size and pathophysiology. Six Sprague-Dawley
      rats were subjected to 90 min transient endovascular occlusion of the M2 segment
      of the middle cerebral artery (M2CAO). Animals were imaged with a nanoScan((r))
      PET/MRI system at 1, 4, 7 and 14 days after M2CAO with a bolus injection of
      [(11)C]PBR28. In the infarct region, we found a significantly increased uptake of
      [(11)C]PBR28 on day 4, 7 and 14 compared to day 1 as well as compared to the
      contralateral cortex. No significant increase was detected in the contralateral
      cortex during the 14 days of imaging. The activation in the infarct region
      gradually decreased between day 4 and day 14. In an additional group of animals
      (n = 26), immunofluorescence studies were performed with antibodies for activated
      microglia/monocytes (Cd11b), phagocytes (Cd68), astrocytes (glial fibrillary
      acidic protein) and TSPO. The TSPO immunofluorescence signal indicated reactive
      microgliosis post injury, corresponding to PET findings. The present clinically
      relevant animal model and TSPO PET ligand appear to be well suited for studies on
      neuroinflammation after ischemic stroke.

PMID- 25601154
TI  - Mathematical modelling suggests a differential impact of beta-transducin repeat
      containing protein paralogues on Wnt/beta-catenin signalling dynamics.
AB  - The Wnt/beta-catenin signalling pathway is involved in the regulation of a
      multitude of cellular processes by controlling the concentration of the
      transcriptional regulator beta-catenin. Proteasomal degradation of beta-catenin
      is mediated by two beta-transducin repeat-containing protein paralogues,
      homologous to Slimb protein (HOS) and F-box/WD repeat-containing protein 1A
      (FWD1), which are functionally interchangeable and thereby considered to function
      redundantly in the pathway. HOS and FWD1 are both regulated by Wnt/beta-catenin
      signalling, albeit in opposite directions, thus establishing interlocked negative
      and positive feedback loops. The functional relevance of the opposite regulation
      of HOS and FWD1 by Wnt/beta-catenin signalling in conjunction with their
      redundant activities in proteasomal degradation of beta-catenin remains
      unresolved. Using a detailed ordinary differential equation model, we
      investigated the specific influence of each individual feedback mechanism and
      their combination on Wnt/beta-catenin signal transduction under wild-type and
      cancerous conditions. We found that, under wild-type conditions, the signalling
      dynamics are predominantly affected by the HOS feedback as a result of a higher
      concentration of HOS than FWD1. Transcriptional up-regulation of FWD1 by other
      signalling pathways reduced the impact of the HOS feedback. The opposite
      regulation of HOS and FWD1 expression by Wnt/beta-catenin signalling allows the
      FWD1 feedback to be employed as a compensation mechanism against aberrant pathway
      activation as a result of a reduced HOS concentration. By contrast, the FWD1
      feedback provides no protection against aberrant activation in adenomatous
      polyposis coli protein mutant cancer cells. 

PMID- 25601155
TI  - Computed tomography navigation combined with endoscope guidance for the removal
      of projectiles in the maxillofacial area: a study of 24 patients.
AB  - The aim of this study was to review recent records on the removal of projectiles
      in the maxillofacial area from patients with firearm wounds, and to summarize our
      experience in the use of computed tomography (CT) navigation combined with an
      endoscope in the treatment of these patients. Twenty-four patients injured by
      firearms and with projectile retention were identified. For surgical planning and
      intraoperative navigation, an iCT system integrating navigation with
      intraoperative CT scanning (iPlan) and an electronic endoscope were used. The
      records of the 24 patients were reviewed retrospectively. All projectiles in
      these cases were accessed and removed with CT navigation combined with endoscope
      guidance; no major complications occurred and the surgery time was reduced
      compared to conventional procedures. Additional incisions were used in 10
      patients; removal of the retained projectile through the original wound is not
      appropriate in certain cases. There was no excessive intraoperative bleeding
      except in one case, and no patient experienced postoperative bleeding. In 29.2%
      of cases, the foreign projectiles involved occupied more than one space. CT
      navigation combined with endoscope guidance is a useful method for removing most
      projectiles retained in the maxillofacial and neck area. 

PMID- 25601156
TI  - Signal clarity: an account of the variability in infant quantity discrimination
      tasks.
AB  - Infants have shown variable success in quantity comparison tasks, with infants of
      a given age sometimes successfully discriminating numerical differences at a 2:3
      ratio but requiring 1:2 and even 1:4 ratios of change at other times. The current
      explanations for these variable results include the two-systems proposal - a
      theoretical framework that suggests that there are multiple systems at play and
      that these systems do not communicate early in infancy, leading to failure in
      certain numerical comparisons. An alternative proposal is that infants may be
      attending to continuous extent dimensions in these tasks rather than number per
      se. However, neither of these two main proposals is independently capable of
      accounting for the previously published data. Recently the Signal Clarity
      Hypothesis was proposed to account for and predict the variability (Cantrell &
      Smith, 2013). According to this hypothesis, infants' variable success may be
      understood from a framework of statistical learning taken together with the
      signal-to-noise ratio generated by control procedures in habituation tasks. Here
      we test specific predictions made by the Signal Clarity Hypothesis. Across four
      experiments assessing 9-month old discriminations of small and large sets (2 vs.
      4 and 3 vs. 4), we demonstrate that infant success can be predicted by this novel
      approach and, further, that infants may discriminate smaller ratios of change
      than previously believed (3:4 numerical change and 2:3 cumulative area change).

PMID- 25601158
TI  - Abundance of live 244Pu in deep-sea reservoirs on Earth points to rarity of
      actinide nucleosynthesis.
AB  - Half of the heavy elements including all actinides are produced in r-process
      nucleosynthesis, whose sites and history remain a mystery. If continuously
      produced, the Interstellar Medium is expected to build-up a quasi-steady state of
      abundances of short-lived nuclides (with half-lives <=100 My), including
      actinides produced in r-process nucleosynthesis. Their existence in today's
      interstellar medium would serve as a radioactive clock and would establish that
      their production was recent. In particular (244)Pu, a radioactive actinide
      nuclide (half-life=81 My), can place strong constraints on recent r-process
      frequency and production yield. Here we report the detection of live interstellar
      (244)Pu, archived in Earth's deep-sea floor during the last 25 My, at abundances
      lower than expected from continuous production in the Galaxy by about 2 orders of
      magnitude. This large discrepancy may signal a rarity of actinide r-process
      nucleosynthesis sites, compatible with neutron-star mergers or with a small
      subset of actinide-producing supernovae. 

PMID- 25601160
TI  - The prevalence of sexual dysfunction in the female health care providers in
      Jeddah, Saudi Arabia.
AB  - The objective of this study was to determine the prevalence of sexual dysfunction
      in Saudi and non-Saudi female health care providers in Jeddah, Saudi Arabia. One 
      hundred twenty (60 Saudi and 60 non-Saudi) sexually active female health care
      professionals in Jeddah, Saudi Arabia, were anonymously surveyed using the
      English version of the female sexual function index questionnaire. The individual
      domain scores for pain, arousal, lubrication, orgasm, satisfaction, pain, and
      overall score for the Saudi and non-Saudi women were calculated and compared. The
      two groups were comparable in demographic characteristics. No statistically
      significant differences were found between Saudi and non-Saudi women in desire (P
      = .22) and arousal scores (P = .47). However, non-Saudi women had significantly
      higher lubrication (P < .001), orgasm (P = .015), satisfaction (P = .004), and
      pain scores (P = .015). The overall scores in Saudi and non-Saudi women were low
      (23.40 +/- 4.50 compared with 26.18 +/- 5.97), but non-Saudi women had a
      significantly higher overall score (P = .005). Taken together, sexual dysfunction
      is prevalent among Saudi and non-Saudi female health care providers, with Saudi
      women demonstrating lower scores in four sexual function domains and the overall
      score. 

PMID- 25601161
TI  - Iliopsoas abscess associated with endovascular infection: an acute case of
      chronic Q fever.
AB  - fever is a zoonosis caused by Coxiella burnetii, which occurs worldwide. After
      acute Q fever infection, 1% to 5% of patients develop chronic Q fever. Chronic Q
      fever usually presents as endocarditis or endovascular infection. The diagnosis
      and localization of chronic Q fever are challenging, as most patients present
      with nonspecific symptoms. Moreover, it often occurs in patients without a known
      episode of acute infection.

PMID- 25601157
TI  - Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical
      use and outcome prediction.
AB  - Hypomethylating agents are able to prolong the overall survival of some patients
      diagnosed with acute myeloid leukemia. The aim of this study was to evaluate the
      clinical use of azacitidine as front-line therapy in unfit acute myeloid leukemia
      (AML) patients and to develop a clinical prediction model to identify which
      patients may benefit more from the drug. One hundred and ten untreated unfit AML
      patients received front-line azacitidine therapy in Spain, and response and
      survival were evaluated in them following European LeukemiaNet (ELN) guidelines.
      A clinical prediction rule was obtained from this population that was validated
      and refined in 261 patients treated in France, Austria and Italy. ELN response
      was achieved in 21.0% of the 371 patients (CI95% 17.0-25.5) and did not depend on
      bone marrow blast cell percentage. Median overall survival was 9.6 months (CI95%
      8.5-10.8) and 40.6% of the patients were alive at 1 year (CI95% 35.5-45.7).
      European ALMA score (E-ALMA), based on performance status, white blood cell
      counts at azacitidine onset and cytogenetics, discriminated three risk groups
      with different survival and response rates. Azacitidine seems a reasonable
      therapeutic option for most unfit AML patients, i.e. those displaying a favorable
      or intermediate E-ALMA score. 

PMID- 25601159
TI  - Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response.
AB  - Ataxia telangiectasia mutated (ATM) mediates DNA damage response by controling
      irradiation-induced foci formation, cell cycle checkpoint, and apoptosis.
      However, how upstream signaling regulates ATM is not completely understood. Here,
      we show that upon irradiation stimulation, ATM associates with and is
      phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the
      site of DNA double-strand breaks. Depletion of endogenous EGFR impairs ATM
      mediated foci formation, homologous recombination, and DNA repair. Moreover,
      pretreatment with an EGFR kinase inhibitor, gefitinib, blocks EGFR and ATM
      association, hinders CHK2 activation and subsequent foci formation, and increases
      radiosensitivity. Thus, we reveal a critical mechanism by which EGFR directly
      regulates ATM activation in DNA damage response, and our results suggest that the
      status of ATM Y370 phosphorylation has the potential to serve as a biomarker to
      stratify patients for either radiotherapy alone or in combination with EGFR
      inhibition. 

PMID- 25601162
TI  - Meteorologic parameters and migraine headache: ED study.
AB  - AIM: Migraine is common in society and is one of the primary causes of chronic
      headache with episodes. In this study, we aimed to determine the role of
      meteorologic parameters and moon phase on triggering migraine attacks and effects
      on the number of patients presenting to the emergency department with migraine
      headaches. MATERIALS AND METHODS: Patients admitted to the emergency department
      due to a migraine headache during a 1-year period were studied retrospectively.
      Correlation between moon phases, pressure, temperature, humidity, wind speed
      values of meteorologic observation, and recording station located in the same
      city and daily number of patients was analyzed. RESULTS: A total of 3491
      patients, of whom 72% (n = 2518) were women, were enrolled. The average daily
      number of patients was 9.6 +/- 4 (3-24). A statistically significant correlation
      was found between the number of daily patients and daily maximum temperature (P =
      .005), mean temperature (P = .013), minimum temperature (P = .041), and daily
      temperature change (P = .003). In addition, a negative correlation was found
      between the daily number of patients presenting to the emergency department and
      daily relative humidity (in percentage; P = .031). No significant relationship
      was found between moon phases and the number of patients. CONCLUSION: We have
      determined that the number of patients admitted to the emergency department with
      migraine headache has increased with high temperature and low humidity and that
      there is no relationship between the number of patients and moon phases.

PMID- 25601163
TI  - The first description of cardiac magnetic resonance findings in a severe scorpion
      envenomation: Is it a stress-induced (Takotsubo) cardiomyopathy like?
AB  - There are more than 1 million cases of scorpion envenomation worldwide. Severe
      complications due to myocardial depression can happen in some patients, mainly
      children. A catecholamine-induced myocarditis probably causes this cardiac
      dysfunction. We describe a case of a 7-year-old boy with a severe scorpion
      envenomation complicated by pulmonary edema in which the cardiac magnetic
      resonance (CMR)was performed during the acute phase. The CMR showed an apical
      ballooning in the left ventricle associated with a left ventricle ejection
      fraction of 29% and a global edema of the midmyocardium and apical myocardiumin
      the T2-weighted triple inversion recovery images. The CMR was repeated after 7
      months and showed complete recovery of the wall motion in the apical region and
      of the myocardial function (left ventricle ejection fraction, 60%) associated
      with normalization of the signal in the T2-weighted triple inversion recovery
      images. These clinical and laboratory findings, mainly the CMR images, are
      similar to those observed in stress-induced cardiomyopathy (Takotsubo)
      reinforcing the hypothesis that the catecholamine's excess has a pivotal function
      in the pathophysiology of the cardiac dysfunction in these 2 conditions.

PMID- 25601164
TI  - Recidivism among ED super users after implementation of a pain protocol.

PMID- 25601165
TI  - One step creation of multifunctional 3D architectured hydrogels inducing bone
      regeneration.
AB  - Structured hydrogels showing form stability and elastic properties individually
      tailorable on different length scales are accessible in a one-step process. They
      support cell adhesion and differentiation and display growing pore size during
      degradation. In vivo experiments demonstrate their efficacy in biomaterial
      induced bone regeneration, not requiring addition of cells or growth factors. 

PMID- 25601166
TI  - Testing item response theory invariance of the standardized Quality-of-life
      Disease Impact Scale (QDIS((r))) in acute coronary syndrome patients:
      differential functioning of items and test.
AB  - PURPOSE: The Quality-of-life (QOL) Disease Impact Scale (QDIS((r))) standardizes
      the content and scoring of QOL impact attributed to different diseases using item
      response theory (IRT). This study examined the IRT invariance of the QDIS
      standardized IRT parameters in an independent sample. METHOD: The differential
      functioning of items and test (DFIT) of a static short-form (QDIS-7) was examined
      across two independent sources: patients hospitalized for acute coronary syndrome
      (ACS) in the TRACE-CORE study (N = 1,544) and chronically ill US adults in the
      QDIS standardization sample. "ACS-specific" IRT item parameters were calibrated
      and linearly transformed to compare to "standardized" IRT item parameters.
      Differences in IRT model-expected item, scale and theta scores were examined. The
      DFIT results were also compared in a standard logistic regression differential
      item functioning analysis. RESULTS: Item parameters estimated in the ACS sample
      showed lower discrimination parameters than the standardized discrimination
      parameters, but only small differences were found for thresholds parameters. In
      DFIT, results on the non-compensatory differential item functioning index (range
      0.005-0.074) were all below the threshold of 0.096. Item differences were further
      canceled out at the scale level. IRT-based theta scores for ACS patients using
      standardized and ACS-specific item parameters were highly correlated (r = 0.995,
      root-mean-square difference = 0.09). Using standardized item parameters, ACS
      patients scored one-half standard deviation higher (indicating greater QOL
      impact) compared to chronically ill adults in the standardization sample.
      CONCLUSION: The study showed sufficient IRT invariance to warrant the use of
      standardized IRT scoring of QDIS-7 for studies comparing the QOL impact
      attributed to acute coronary disease and other chronic conditions.

PMID- 25601167
TI  - Reliability of automatic vibratory equipment for ultrasonic strain measurement of
      the median nerve: common mistake.

PMID- 25601168
TI  - Wheat allergy in children evaluated with challenge and IgE antibodies to wheat
      components.
AB  - INTRODUCTION: Wheat sensitization is common but IgE antibodies (IgE-abs) to wheat
      are not predictive of clinical symptoms in children with suspected wheat allergy.
      Wheat allergen components other than omega-5 gliadin have not been well studied.
      Our aim was to characterize the clinical profile and investigate the value of
      adding measurements of IgE-abs to wheat components in a group of children with a
      doctor's diagnosed wheat allergy. METHOD: Sixty-three children with a doctor's
      diagnosis of wheat allergy confirmed sensitization to wheat and, on a wheat
      elimination diet, went through oral wheat challenges or had a convincing recent
      history of wheat allergy. IgE-ab to omega-5 gliadin, low molecular weight
      glutenin (LMW-glutenin), high molecular weight glutenin (HMW-glutenin) and a
      native gliadin preparation containing alpha-, beta-, gamma-, and omega-gliadin
      (gliadin) were analyzed. RESULTS: Twenty-six children were positive in challenge,
      while six children were regarded as wheat allergic due to recent anaphylactic
      reactions. The IgE-ab levels to all four wheat components were significantly
      higher in the group with wheat allergy compared to the group with no wheat
      allergy (p < 0.0001). Also, the severity of symptoms at challenge correlated with
      the IgE-ab levels to all four components (p < 0.05). IgE-ab levels to omega-5
      gliadin correlated best with challenge outcome, and by additional analysis of
      gliadin, HMW- and LMW-glutenin IgE-abs all challenge positive children could be
      identified. CONCLUSION: Many children diagnosed as wheat allergic have outgrown
      their allergy and are unnecessarily on a wheat-free diet. The levels of IgE-ab to
      wheat gluten-derived components correlated well with wheat challenge outcome and
      severity.

PMID- 25601169
TI  - Self-powered microneedle-based biosensors for pain-free high-accuracy measurement
      of glycaemia in interstitial fluid.
AB  - In this work a novel self-powered microneedle-based transdermal biosensor for
      pain-free high-accuracy real-time measurement of glycaemia in interstitial fluid
      (ISF) is reported. The proposed transdermal biosensor makes use of an array of
      silicon-dioxide hollow microneedles that are about one order of magnitude both
      smaller (borehole down to 4um) and more densely-packed (up to
      1*10(6)needles/cm(2)) than state-of-the-art microneedles used for biosensing so
      far. This allows self-powered (i.e. pump-free) uptake of ISF to be carried out
      with high efficacy and reliability in a few seconds (uptake rate up to 1ul/s) by
      exploiting capillarity in the microneedles. By coupling the microneedles
      operating under capillary-action with an enzymatic glucose biosensor integrated
      on the back-side of the needle-chip, glucose measurements are performed with high
      accuracy (+/-20% of the actual glucose level for 96% of measures) and
      reproducibility (coefficient of variation 8.56%) in real-time (30s) over the
      range 0-630mg/dl, thus significantly improving microneedle-based biosensor
      performance with respect to the state-of-the-art. 

PMID- 25601170
TI  - Prevalence and risk factors of atherothrombotic events among 1054 hemophilia
      patients: a population-based analysis.
AB  - INTRODUCTION: Reports on the prevalence and risk factors of atherothrombotic
      events (AEs) are conflicting in persons with hemophilia (PWH). METHODS: This
      study evaluated the prevalence and risk factors of AEs among 1054 male hemophilia
      patients, using data collected from Taiwan's National Health Insurance Research
      Database between 1997 and 2010, by comparing variable to those of an unaffected
      10540 age- and gender-matched general population. RESULTS: The proportions of all
      AEs among PWH, including 26 ischemic stroke, 29 coronary artery disease and 5
      peripheral arterial disease were comparable to those in the general population.
      The mean age at diagnosis of AE among PWH was younger than that in the general
      population: 49.0 (95% CI, 43.6-54.5) and 55.8 years (95% CI, 54.5-57.0), P =
      0.019, respectively. PWH with Chronic Obstructive Pulmonary Disease (COPD),
      hypertension, and hyperlipidemia were associated with greater risk for the
      occurrence of AEs, with hazard ratios (95% CI) of 3.42 (1.25-9.38), 4.15 (2.11
      8.17), and 2.84 (1.39-5.79), respectively. PWH who needed replacement therapy had
      a lower risk of AEs than those who did not need, with a hazard ratio (95% CI) of
      0.41 (0.21-0.81). CONCLUSIONS: The study indicated the prevalence of AEs among
      PWH was comparable to that of the general population. AEs appeared at an earlier
      age among PWH. COPD, hypertension, and hyperlipidemia were risk factors for AEs.
      PWH who needed replacement therapy may have a lower risk of AEs.

PMID- 25601171
TI  - Response of platelet concentrates to pressure and temperature changes without
      impairment of the in vitro function.
AB  - BACKGROUND: Rapid platelet concentrate (PC) transfusion is crucial for hemostatic
      resuscitation. Pressure-aided and warmed transfusion combined with pneumatic tube
      system (PTS) transport from the laboratory to the operating theatre offers a
      potentially rapid delivery technique. The aim of this study is a quantitative
      assessment of in vitro platelet function after PTS transport followed by warmed
      and/or pressure-aided mock transfusions. METHODS: Ten PC samples entered a single
      PTS run and were subsequently aliquoted for testing. PCs were warmed in a blood
      warmer and/or subjected to pressure-aided mock transfusion at 300 mm Hg on day 2
      or day 7 after collection. Platelet function was assessed using light
      transmission aggregometry and multiple-electrode aggregometry to measure the
      response to ADP, arachidonic acid, collagen, and thrombin-receptor activating
      peptide. Data were analyzed with non-parametric testing; P<0.05 was considered
      statistically significant. RESULTS: Single PTS transport markedly reduced ADP
      response in fresh PCs. Seven-day storage had a pronounced effect on both ADP and
      collagen response. All other tested platelet agonists revealed preserved
      function. Subsequent warming and/or application of pressure did not significantly
      compromise platelet function. CONCLUSIONS: Pressure-aided plus warmed transfusion
      and PTS transport was not found to be detrimental to the PC. Further clinical
      studies are required to determine safety and efficacy of the product.

PMID- 25601172
TI  - Metabolic syndrome, platelet activation and the development of transient ischemic
      attack or thromboembolic stroke.
AB  - Stroke is the second most common cause of mortality in the world today, where
      transient ischemic attack (TIA) is a period of focal ischemia, the symptoms of
      which resemble a thromboembolic stroke. Contrary to stroke, TIA symptoms
      typically last less than one hour and necrosis is absent. Stroke is often
      preceded by TIA, making it an important predictor of future ischemic events. The
      causal role of atherosclerosis in the development of TIA is well established,
      however, research indicates that the atherosclerotic process begins years earlier
      with the development of metabolic syndrome, which affects approximately 45% of
      the adult population worldwide. Metabolic syndrome is present if three or more of
      the following is present: increased waist circumference, increased triglycerides,
      decreased HDL, increased fasting glucose and hypertension. This syndrome causes
      systemic inflammation that activates the coagulation system and may cause the
      formation of pathological thrombi. The role of platelets in stroke has been
      studied and platelet activation pathways identified. ADP and thromboxane A(2) are
      the most common activators of platelets in normal physiology. Several
      pharmacological treatments have been employed to prevent the activation of
      platelets, the most common of which include aspirin and P2Y(12)-inhibitors.
      Although treatment is administered strokes and subsequent TIAs are very common in
      individuals that suffered an initial event. This indicates that research needs to
      be done in order to elucidate new therapeutic targets, but also to better treat
      ischemic events to not only decrease the amount of recurring events but also
      decrease stroke mortality worldwide.

PMID- 25601173
TI  - A simple prediction score for developing a hospital-acquired infection after
      acute ischemic stroke.
AB  - BACKGROUND: Hospital-acquired infections (HAIs) are a major cause of morbidity
      and mortality in acute ischemic stroke patients. Although prior scoring systems
      have been developed to predict pneumonia in ischemic stroke patients, these
      scores were not designed to predict other infections. We sought to develop a
      simple scoring system for any HAI. METHODS: Patients admitted to our stroke
      center (July 2008-June 2012) were retrospectively assessed. Patients were
      excluded if they had an in-hospital stroke, unknown time from symptom onset, or
      delay from symptom onset to hospital arrival greater than 48 hours. Infections
      were diagnosed via clinical, laboratory, and imaging modalities using standard
      definitions. A scoring system was created to predict infections based on baseline
      patient characteristics. RESULTS: Of 568 patients, 84 (14.8%) developed an
      infection during their stays. Patients who developed infection were older (73
      versus 64, P < .0001), more frequently diabetic (43.9% versus 29.1%, P = .0077),
      and had more severe strokes on admission (National Institutes of Health Stroke
      Scale [NIHSS] score 12 versus 5, P < .0001). Ranging from 0 to 7, the overall
      infection score consists of age 70 years or more (1 point), history of diabetes
      (1 point), and NIHSS score (0-4 conferred 0 points, 5-15 conferred 3 points, >15
      conferred 5 points). Patients with an infection score of 4 or more were at 5
      times greater odds of developing an infection (odds ratio, 5.67; 95% confidence
      interval, 3.28-9.81; P < .0001). CONCLUSION: In our sample, clinical, laboratory,
      and imaging information available at admission identified patients at risk for
      infections during their acute hospitalizations. If validated in other
      populations, this score could assist providers in predicting infections after
      ischemic stroke.

PMID- 25601174
TI  - iScore for predicting institutional care after ischemic stroke: a population
      based study.
AB  - BACKGROUND: We assessed whether the iScore could predict the need for poststroke
      institutional care. METHODS: Patients with acute ischemic stroke living in Dijon,
      France, were recorded between 2006 and 2011, using a population-based stroke
      registry. The iScore was calculated for each patient. A logistic regression model
      was used to assess the performance of the iScore for predicting the need for
      placement in a care institution. The discrimination and calibration of the model
      were assessed using the c statistic and the Hosmer-Lemeshow goodness-of-fit test,
      respectively. RESULTS: Of the 1199 patients recorded, 124 were excluded because
      of early death and 95 because of missing for variables included in the iScore. Of
      the remaining 980 patients, 522 (53.3%) returned home and 458 (46.7%) required
      placement in a care institution. The median iScore was 123 (interquartile range,
      97-148), and the proportion of patients who required placement in a care
      institution increased with each quintile of risk score. The discrimination of the
      model was good with a c statistic of .75 (95% confidence interval, .72-.78), as
      was calibration (P = .35). CONCLUSIONS: The iScore could be useful for predicting
      the need for placement in a care institution in ischemic stroke patients. Further
      studies are required to confirm this finding.

PMID- 25601175
TI  - Awareness of stroke risk factors and warning signs in Nigerian adolescents
      compared with adults.
AB  - BACKGROUND: Stroke, a significant health problem affecting adults, is increasing
      among younger age groups, particularly because of changing lifestyles. The aim of
      the study was to compare the awareness of stroke risk factors and warning signs
      among students and teachers in selected secondary schools in Osun State, Nigeria.
      METHODS: This was a cross-sectional survey involving 703 (589 students and 114
      teachers) respondents in selected secondary schools in Osun, Nigeria. Information
      on the awareness of stroke risk factors and warning signs was collected with the
      aid of a structured questionnaire. RESULTS: Hypertension (69.4%) was the most
      commonly identified stroke risk factor, with more teachers (79.8%) identifying
      correctly than the students (67.4%). Weakness (51.9%) was the most commonly
      identified warning sign of stroke with more students (53.8%) identifying
      correctly than the teachers (42.1%). There were significant differences in the
      awareness of some risk factors (age, obesity, family history, alcohol use, diet,
      transient ischemic attack, and hyperlipidemia) and warning signs (dizziness,
      weakness, and vision problems) between students and teachers. Predictors for
      adequate awareness of risk factors were being a teacher, not being obese and
      being hypertensive, whereas predictors for adequate awareness of warning signs
      were stroke in the family and being hypertensive. CONCLUSIONS: There was
      inadequate awareness of risk factors and warning signs among the respondents with
      students having better awareness of warning signs and teachers having better
      awareness of risk factors. Stroke campaigns should emphasize stroke risk factors
      particularly among adolescents and warning signs in adults. The use of media,
      particularly television, is recommended.

PMID- 25601177
TI  - Intravenous versus intra-arterial thrombolysis for anterior circulation stroke
      secondary to large vessel occlusion.

PMID- 25601176
TI  - Increased VEGF and decreased SDF-1alpha in patients with silent brain infarction
      are associated with better prognosis after first-ever acute lacunar stroke.
AB  - BACKGROUND: Pre-existing silent brain infarctions (SBIs) have been reported to be
      associated with better outcomes after first-ever symptomatic ischemic stroke,
      although the mechanism of this remains unclear. We investigated the association
      between SBIs, outcomes of acute lacunar infarction, and biomarkers including
      vascular endothelial growth factor (VEGF), stromal cell-derived factor-1alpha
      (SDF-1alpha), macrophage migration inhibitory factor (MIF), and high-mobility
      group box-1 (HMGB1). METHODS: A total of 68 consecutive patients diagnosed with
      first-ever lacunar infarction (<20 mm) within 24 hours of symptom onset were
      included in this study. Clinical, laboratory, and imaging data were obtained.
      Plasma levels of VEGF, SDF-1alpha, MIF, and HMGB1 were assessed using Enzyme
      Linked Immunosorbent Assay kits. RESULTS: SBIs were noted in 31 of the 68
      patients. Although the initial National Institutes of Health Stroke Scale scores
      were not related with the presence of SBIs (P = .313), patients with SBIs had
      better outcomes at 3 months (P = .029). Additionally, plasma VEGF levels were
      higher (P = .035) and SDF-1alpha levels were lower (P < .001) in patients with
      SBIs. Logistic regression analysis indicated that VEGF and SDF-1alpha were
      independently associated with the presence of SBIs. CONCLUSIONS: SBIs are
      associated with favorable outcomes in patients with first-ever acute lacunar
      infarction and higher levels of VEGF, and lower levels of SDF-1alpha in these
      patients may contribute to their more favorable prognosis.

PMID- 25601178
TI  - Cardiac troponin I after carotid endarterectomy in different cardiac risk
      patients.
AB  - BACKGROUND: We compared postoperative cardiac damage, defined as cardiac troponin
      I (cTnI) elevation, in low, medium, and high cardiac risk patients, after carotid
      endarterectomy (CEA). METHODS: The Vascular Study Group of New England Cardiac
      Risk Index (VSG-CRI) criteria for stratifying patients considered for vascular
      surgery into low, medium, and high cardiac risk groups were used prospectively.
      For all patients (n = 324), cTnI value assessments were made before surgery and
      on postoperative days 1, 3, and 7. Postoperative cTnI values ranging from .05 to
      .5 ng/mL were classified as myocardial ischemia; values more than .5 ng/mL were
      classified as myocardial infarction. Cardiac damage was defined as either
      myocardial ischemia or infarction. RESULTS: Mortality was .003%, stroke rate was
      null, and symptomatic myocardial infarction was null as well. Low-risk patients
      (16 of 140) and medium-risk patients (28 of 160) increased their troponin levels
      on days 1 and 3 postoperatively. However, none of the high-risk patients (n = 24)
      showed any postoperative cardiac damage. Low and medium cardiac risk patients
      showed higher troponin values on each separate day, in comparison with high
      cardiac risk patients. CONCLUSIONS: CEA is followed by a high incidence of
      asymptomatic cTnI increase that is associated with late cardiac events. However,
      high cardiac risk patients as defined by the VSG-CRI criteria do not seem to
      suffer higher cardiac damage after CEA compared with low and medium cardiac risk
      patients.

PMID- 25601179
TI  - Influence of antithrombotics on the etiology of intracerebral hemorrhage.
AB  - BACKGROUND: To determine the influence of antithrombotic use on the etiology of
      primary intracerebral hemorrhage (ICH). METHODS: We conducted a retrospective
      review of consecutive patients admitted with primary ICH from 2009 to 2012. Data
      recorded included age, history of hypertension, and use of antithrombotic
      medications. Imaging was reviewed to determine hemorrhage location and the
      presence and the location of any microhemorrhages. Etiologies were classified
      using a predetermined algorithm, which was based on existing literature. RESULTS:
      In total, 292 patients were included. Median age was 74 years (range, 18-101),
      and 52% were male (n = 151). Hemorrhage etiology was hypertension in 50.6% (n =
      148), indeterminate in 29.5% (n = 86), and cerebral amyloid angiopathy (CAA) in
      19.9% (n = 58). Most patients were on antithrombotics (61.3%, n = 179). Nearly
      half of the patients (49%) were 75 years of age or older, and the most common
      etiology in this group was hypertension (n = 77, 53%). There was a nonsignificant
      trend toward older age and CAA-ICH (median age, 77 years; interquartile range
      [IQR], 70-82 years) compared with other causes (median age, 74 years; IQR, 61-82
      years; P = .07). There was no difference between CAA-ICH and other-cause ICH with
      respect to proportion of patients on antithrombotics in general (67% versus 60%;
      P = .367) or anticoagulants in particular (24% versus 25%; P = 1.000).
      CONCLUSIONS: The most common ICH etiology in this study was hypertension,
      regardless of age. Our findings do not suggest that the higher occurrence of ICH
      in older patients or in patients with CAA-associated ICH is because of a higher
      frequency of anticoagulant use.

PMID- 25601180
TI  - Cerebral amyloid angiopathy causing large contralateral hemorrhage during surgery
      for lobar hemorrhage: a case report.
AB  - We report a rare case of cerebral amyloid angiopathy (CAA) causing large
      contralateral hemorrhage during surgery for lobar hemorrhage. A 62-year-old woman
      presented with lobar hemorrhage in the left frontal and parietal lobes recurring
      over the previous 1 month. Because we could not detect the origin of the lobar
      hemorrhage, we performed a biopsy around the lobar hemorrhage site with the
      removal of a hematoma. During the surgery, we identified acute brain swelling
      without bleeding from the operative field. Intraoperative computed tomography
      demonstrated new large lobar hemorrhage of the right parietal lobe, which we
      could promptly remove. Specimens around hematomas on both sides were
      pathologically diagnosed as CAA on immunohistochemical examination. After the
      surgery, she suffered from lobar hemorrhage three times in the space of only 3
      months. To the best of our knowledge, there has been no reported case of CAA
      causing intracranial hemorrhage of another lesion during surgery. Neurosurgeons
      should know a possibility of intraoperative hemorrhage in surgeries for lobar
      hemorrhage caused by CAA.

PMID- 25601181
TI  - Methylene Blue Improves Brain Mitochondrial ABAD Functions and Decreases Abeta in
      a Neuroinflammatory Alzheimer's Disease Mouse Model.
AB  - Methylene blue (MB) phase II clinical trials reported improvements in cognitive
      functions of Alzheimer's disease (AD) patients. Regarding MB mechanism of action,
      its antioxidant and mitochondrial protective effects have been previously
      described. In relation to AD, it has been recently reported that MB reduced
      amyloid beta (Abeta) levels in AD models. The mitochondrial enzyme amyloid
      binding alcohol dehydrogenase (ABAD) has been shown to bind Abeta inducing
      mitochondrial dysfunction, providing a direct relation between Abeta toxicity and
      mitochondrial dysfunction occurring in AD. Since it has been reported that
      inhibiting ABAD protects mitochondrial functions and prevents Abeta-induced
      toxicity, the aim of the current study was to investigate if the protective
      effects of MB could be associated with an effect on ABAD levels and functions.
      The current study shows that MB is able to enhance cell viability, reduce both
      reactive oxygen species levels and importantly Abeta oligomers in a
      lipopolysaccharide (LPS) mouse model. Interestingly, ABAD levels were increased
      in the brains of the LPS mouse model and MB treatment was able to reduce its
      levels. Given that regulation of the estradiol level is a well-established
      function of ABAD, brain estradiol level was compared in LPS mouse model and in MB
      treated mice. The results of the current study show that MB treatment is able to
      improve significantly the LPS-induced decrease of estradiol levels in mice
      brains, indicating its ability to modulate both levels and function of ABAD.
      These results give a new insight to possible mechanisms of MB in AD. 

PMID- 25601183
TI  - Origin of degradation phenomenon under drain bias stress for oxide thin film
      transistors using IGZO and IGO channel layers.
AB  - Top-gate structured thin film transistors (TFTs) using In-Ga-Zn-O (IGZO) and In
      Ga-O (IGO) channel compositions were investigated to reveal a feasible origin for
      degradation phenomenon under drain bias stress (DBS). DBS-driven instability in
      terms of V(TH) shift, deviation of the SS value, and increase in the on-state
      current were detected only for the IGZO-TFT, in contrast to the IGO-TFT, which
      did not demonstrate V(TH) shift. These behaviors were visually confirmed via
      nanoscale transmission electron microscopy and energy-dispersive x-ray
      spectroscopy observations. To understand the degradation mechanism, we performed
      ab initio molecular dynamic simulations on the liquid phases of IGZO and IGO. The
      diffusivities of Ga and In atoms were enhanced in IGZO, confirming the
      degradation mechanism to be increased atomic diffusion.

PMID- 25601184
TI  - Prescribing behavior of general practitioners: competition matters.
AB  - BACKGROUND: General Practitioners (GP) have limited means to compete. As quality
      is hard to observe by patients, GPs have incentives to signal quality by using
      instruments patients perceive as quality. OBJECTIVES: I investigate whether GPs
      prescribe more units when confronted with more competition. As there is no
      monetary benefit in doing so, this type of (perceived) quality competition
      originates from GPs satisfying patients' expectations. METHOD: Market level data
      on per capita and per contact number of items prescribed by GPs is studied for
      the Belgian market of General Practitioners. I hypothesize that GP competition
      has a positive impact on the prescribed volume, after controlling for medical
      needs and GP characteristics. Properly controlling for medical needs implies the
      use of a two-stage linear regression model. FINDINGS: The analysis indicates that
      a higher number of GPs per capita results in a higher number of units prescribed
      by GPs, both per capita and per contact. This is consistent with quality
      competition in the GP market, while inconsistent with alternatives explanations
      (GP scarcity, GP inducement and GP dispersing prescription in time). CONCLUSION:
      GPs prescribe more units when there is more competition to satisfy patients'
      expectations. The paper thus presents empirical evidence of (perceived) quality
      competition.

PMID- 25601182
TI  - Is there evidence that walking groups have health benefits? A systematic review
      and meta-analysis.
AB  - OBJECTIVE: To assess the health benefits of outdoor walking groups. DESIGN:
      Systematic review and meta-analysis of walking group interventions examining
      differences in commonly used physiological, psychological and well-being outcomes
      between baseline and intervention end. DATA SOURCES: Seven electronic databases,
      clinical trial registers, grey literature and reference lists in English language
      up to November 2013. ELIGIBILITY CRITERIA: Adults, group walking outdoors with
      outcomes directly attributable to the walking intervention. RESULTS: Forty-two
      studies were identified involving 1843 participants. There is evidence that
      walking groups have wide-ranging health benefits. Meta-analysis showed
      statistically significant reductions in mean difference for systolic blood
      pressure -3.72 mm Hg (-5.28 to -2.17) and diastolic blood pressure -3.14 mm Hg (
      4.15 to -2.13); resting heart rate -2.88 bpm (-4.13 to -1.64); body fat -1.31% (
      2.10 to -0.52), body mass index -0.71 kg/m(2) (-1.19 to -0.23), total cholesterol
      -0.11 mmol/L (-0.22 to -0.01) and statistically significant mean increases in
      VO(2max) of 2.66 mL/kg/min (1.67-3.65), the SF-36 (physical functioning) score
      6.02 (0.51 to 11.53) and a 6 min walk time of 79.6 m (53.37-105.84). A
      standardised mean difference showed a reduction in depression scores with an
      effect size of -0.67 (-0.97 to -0.38). The evidence was less clear for other
      outcomes such as waist circumference fasting glucose, SF-36 (mental health) and
      serum lipids such as high-density lipids. There were no notable adverse side
      effects reported in any of the studies. CONCLUSIONS: Walking groups are effective
      and safe with good adherence and wide-ranging health benefits. They could be a
      promising intervention as an adjunct to other healthcare or as a proactive health
      promoting activity.

PMID- 25601185
TI  - Photosensitized oxidation of aryl benzyl sulfoxides. Evidence for nucleophilic
      assistance to the C-s bond cleavage of aryl benzyl sulfoxide radical cations.
AB  - The radical cations of a series of aryl benzyl sulfoxides (4-X
      C6H4CH2SOC6H4Y(+*)) have been generated by photochemical oxidation of the parent
      sulfoxides sensitized by 3-cyano-N-methylquinolinium perchlorate (3-CN
      NMQ(+)ClO4(-)). Steady-state photolysis experiments showed the prevailing
      formation of benzylic products deriving from the C-S fragmentation in the radical
      cations, together with sulfur-containing products. Formation of sulfoxide radical
      cations was unequivocally established by laser flash photolysis experiments
      showing the absorption bands of 3-CN-NMQ(*) (lambdamax = 390 nm) and of the
      radical cations (lambdamax = 500-620 nm). The decay rate constants of radical
      cations, determined by LFP experiments, decrease by increasing the electron
      donating power of the arylsulfinyl Y substituent and to a smaller extent by
      increasing the electron-withdrawing power of the benzylic X substituent. A
      solvent nucleophilic assistance to the C-S bond cleavage has been suggested,
      supported by the comparison of substituent effects on the same process occurring
      in aryl tert-butyl sulfoxide radical cations. DFT calculations, performed to
      determine the bond dissociation free energy in the radical cations, the
      transition state energies associated with the unimolecular C-S bond cleavage, and
      the charge and spin delocalized on their structures, were also useful to endorse
      the nucleophilic assistance to the C-S scission. 

PMID- 25601186
TI  - The use of imaging technology in the assessment of the fetal inflammatory
      response syndrome-imaging of the fetal thymus.
AB  - The fetal inflammatory response syndrome (FIRS) describes a state of extensive
      fetal multi organ involvement during chorioamnionitis, and is associated with
      grave implications on perinatal outcome. The syndrome has been linked to the
      preterm parturition syndrome and is associated with inflammation/infection
      processes in most of the fetal organs. The fetal thymus, a major organ in the
      developing immune system involutes during severe neonatal disease and has been
      shown to be smaller in fetuses with FIRS. Various methods for imaging of the
      fetal thymus and measurement are described. Currently the only method to diagnose
      FIRS prenatally is through amniocentesis. We suggest that women who are admitted
      with preterm labor with intact membranes and those with PPROM should have a
      detailed sonographic examination of the fetal thymus as a surrogate marker of
      fetal involvement in intrauterine infection/inflammation processes.

PMID- 25601187
TI  - Ruxolitinib: a review of its use in patients with myelofibrosis.
AB  - Ruxolitinib (Jakavi((r)), Jakafi((r))) is an orally administered inhibitor of
      Janus kinases (JAK) 1 and 2 used in the management of patients with
      myelofibrosis. Clinical trials with ruxolitinib, notably the phase III COMFORT-I
      and -II studies and their extensions, have demonstrated marked and durable
      clinical benefits in terms of reductions in splenomegaly and disease-related
      symptoms in patients with intermediate-2 or high-risk myelofibrosis. Ruxolitinib
      was also associated with improvements in health-related quality of life and
      functioning. Despite the crossover of patients in control groups to ruxolitinib,
      results of the COMFORT studies and their extensions indicate a survival advantage
      for patients randomized to ruxolitinib. The beneficial effects of ruxolitinib
      were observed across subgroups of myelofibrosis patients, including those not
      harbouring the JAK2V617F mutation. Improvements in splenomegaly and disease
      related symptoms were also observed in a trial in Japanese/Asian patients with
      myelofibrosis and in myelofibrosis patients with a low baseline platelet count.
      Dose-related anaemia and thrombocytopenia were common in clinical trials with
      ruxolitinib, but rarely led to discontinuation of therapy and were managed with
      dosage modifications and/or transfusions of packed red blood cells. In addition
      to the USA and EU, ruxolitinib is now approved in a number of other countries,
      including Japan, and remains the only approved drug for the treatment of
      myelofibrosis, although various other agents are undergoing investigation.
      Appropriate monitoring and dosage titration are important to achieve optimal
      clinical benefits of ruxolitinib. Further research, including studies evaluating
      ruxolitinib-based combination therapy, may also help to optimise treatment. 

PMID- 25601188
TI  - Favorable response to trastuzumab plus irinotecan combination therapy in two
      patients with HER2-positive relapsed small-cell lung cancer.
AB  - Small-cell lung cancer (SCLC) easily recurs with multidrug resistance phenotype.
      However, standard therapeutic strategies for relapsed-SCLC remain unestablished.
      Human epidermal growth factor receptor 2 (HER2) expression correlates with poor
      prognosis in extensive disease-SCLC. We have reported previously that HER2
      expression is upregulated when HER2-positive SCLC cells acquire chemoresistance,
      and also demonstrated that trastuzumab exerts significant antitumor activity
      toward HER2-upregulated chemoresistant SCLC, mainly via antibody-dependent cell
      mediated cytotoxicity mechanism. Based on these preclinical data, we treated two
      patients with HER2-positive SCLC by combination of trastuzumab (6 mg/kg, day 1)
      and irinotecan (80 mg/m(2), days 1 and 8) every 21 days as the third-line
      chemotherapy following two prior regimens, first-line carboplatin plus etoposide
      and second-line amrubicin. One patient achieved partial response after the first
      cycle and received 6 cycles in total without disease progression for 4.5 months.
      The other also received 4 cycles and kept stable disease for 3.5 months. This
      treatment can be continued safely at an outpatient clinic without any severe
      adverse event. In conclusion, trastuzumab plus irinotecan chemotherapy is
      promising and feasible against HER2-positive relapsed SCLC. Further clinical
      studies are encouraged to confirm the antitumor efficacy of trastuzumab in SCLC.

PMID- 25601189
TI  - Rare heterozygous truncating variations and risk of autism spectrum disorder:
      Whole-exome sequencing of a multiplex family and follow-up study in a Japanese
      population.
AB  - AIMS: Rare heterozygous truncating variations in multiplex families with autism
      spectrum disorder (ASD) are suggested to play a major role in the genetic
      etiology of ASD. To further investigate the role of rare heterozygous truncating
      variations, we performed whole-exome sequencing (WES) in a multiplex ASD family
      with four affected individuals (two siblings and two maternal cousins), and a
      follow-up case-control study in a Japanese population. METHODS: WES was performed
      in four individuals (a proband, his affected and unaffected siblings, and their
      putative carrier mother) from the multiplex ASD family. Rare heterozygous
      truncating variations prioritized in WES were genotyped in 243 patients and 667
      controls. RESULTS: By WES of the multiplex family, we prioritized two rare
      heterozygous truncating variations, RPS24 Q191X and CD300LF P261fsX266. However,
      we did not identify these variations in patients or controls in the follow-up
      study. CONCLUSIONS: Our findings suggest that two rare heterozygous truncating
      variations (RPS24 Q191X and CD300LF P261fsX266) are risk candidates for ASD.

PMID- 25601190
TI  - Let bone and muscle talk together: a study of real and virtual dissection and its
      implications for femoral musculoskeletal structure of chimpanzees.
AB  - Proximal femoral morphology and associated musculature are of special relevance
      to the understanding of hominoid locomotor systems. Knowledge of bone-muscle
      correspondence in extant hominoids forms an important comparative basis for
      inferring structure-function relationships in fossil hominids. However, there is
      still a lack of consensus on the correspondence between muscle attachment sites
      and surface morphology of the proximal femoral diaphysis in chimpanzees. Two
      alternative observations have been proposed regarding the attachment site
      positions of gluteus maximus (GM) and vastus lateralis (VL) relative to two
      prominent surface features of the proximal femoral diaphysis, the lateral spiral
      pilaster and the inferolateral fossa. Here, we use a combination of virtual and
      physical dissection in an attempt to identify the exact correspondence between
      muscle attachment sites and osteological features in two specimens of Pan
      troglodytes verus. The results show that the insertion of the GM tendon is
      consistently inferolateral to the lateral spiral pilaster, and that a part of the
      inferolateral fossa consistently forms the attachment site of the VL muscular
      fibers. While overall musculoskeletal features are similar in the two specimens
      examined in this study, GM and VL exhibit different degrees of segregation at the
      level of the inferolateral fossa. One specimen exhibited tendinous GM fibers
      penetrating the posteromedial part of VL, with both GM and VL inserting at the
      inferolateral fossa. In the other specimen, GM and VL were separated by a lateral
      intermuscular septum, which inserted into the inferolateral fossa. Variation of
      proximal femoral muscle attachments in chimpanzees is thus greater than
      previously thought. Our results indicate that a conspicuous osteological feature
      such as the inferolateral fossa does not necessarily correspond to the attachment
      site of a single muscle, but could serve as a boundary region between two
      muscles. Caution is thus warranted when interpreting the surface topography of
      muscle attachment sites and inferring locomotor functions. 

PMID- 25601191
TI  - NF-kappaB-direct activation of microRNAs with repressive effects on monocyte
      specific genes is critical for osteoclast differentiation.
AB  - BACKGROUND: Monocyte-to-osteoclast conversion is a unique terminal
      differentiation process that is exacerbated in rheumatoid arthritis and bone
      metastasis. The mechanisms implicated in upregulating osteoclast-specific genes
      involve transcription factors, epigenetic regulators and microRNAs (miRNAs). It
      is less well known how downregulation of osteoclast-inappropriate genes is
      achieved. RESULTS: In this study, analysis of miRNA expression changes in
      osteoclast differentiation from human primary monocytes revealed the rapid
      upregulation of two miRNA clusters, miR-212/132 and miR-99b/let-7e/125a. We
      demonstrate that they negatively target monocyte-specific and immunomodulatory
      genes like TNFAIP3, IGF1R and IL15. Depletion of these miRNAs inhibits osteoclast
      differentiation and upregulates their targets. These miRNAs are also upregulated
      in other inflammatory monocytic differentiation processes. Most importantly, we
      demonstrate for the first time the direct involvement of Nuclear Factor kappa B
      (NF-kappaB) in the regulation of these miRNAs, as well as with their targets,
      whereby NF-kappaB p65 binds the promoters of these two miRNA clusters and NF
      kappaB inhibition or depletion results in impaired upregulation of their
      expression. CONCLUSIONS: Our results reveal the direct involvement of NF-kappaB
      in shutting down certain monocyte-specific genes, including some anti
      inflammatory activities, through a miRNA-dependent mechanism for proper
      osteoclast differentiation.

PMID- 25601193
TI  - Matching for Human Leukocyte Antigens (HLA) in corneal transplantation - to do or
      not to do.
AB  - As many patients with severe corneal disease are not even considered as
      candidates for a human graft due to their high risk of rejection, it is essential
      to find ways to reduce the chance of rejection. One of the options is proper
      matching of the cornea donor and recipient for the Human Leukocyte Antigens
      (HLA), a subject of much debate. Currently, patients receiving their first
      corneal allograft are hardly ever matched for HLA and even patients undergoing a
      regraft usually do not receive an HLA-matched graft. While anterior and posterior
      lamellar grafts are not immune to rejection, they are usually performed in low
      risk, non-vascularized cases. These are the cases in which the immune privilege
      due to the avascular status and active immune inhibition is still intact. Once
      broken due to infection, sensitization or trauma, rejection will occur. There is
      enough data to show that when proper DNA-based typing techniques are being used,
      even low risk perforating corneal transplantations benefit from matching for HLA
      Class I, and high risk cases from HLA Class I and probably Class II matching.
      Combining HLA class I and class II matching, or using the HLAMatchmaker could
      further improve the effect of HLA matching. However, new techniques could be
      applied to reduce the chance of rejection. Options are the local or systemic use
      of biologics, or gene therapy, aiming at preventing or suppressing immune
      responses. The goal of all these approaches should be to prevent a first
      rejection, as secondary grafts are usually at higher risk of complications
      including rejections than first grafts. 

PMID- 25601192
TI  - Modeling the Impact of School-Based Universal Depression Screening on Additional
      Service Capacity Needs: A System Dynamics Approach.
AB  - Although it is widely known that the occurrence of depression increases over the
      course of adolescence, symptoms of mood disorders frequently go undetected. While
      schools are viable settings for conducting universal screening to systematically
      identify students in need of services for common health conditions, particularly
      those that adversely affect school performance, few school districts routinely
      screen their students for depression. Among the most commonly referenced barriers
      are concerns that the number of students identified may exceed schools' service
      delivery capacities, but few studies have evaluated this concern systematically.
      System dynamics (SD) modeling may prove a useful approach for answering questions
      of this sort. The goal of the current paper is therefore to demonstrate how SD
      modeling can be applied to inform implementation decisions in communities. In our
      demonstration, we used SD modeling to estimate the additional service demand
      generated by universal depression screening in a typical high school. We then
      simulated the effects of implementing "compensatory approaches" designed to
      address anticipated increases in service need through (1) the allocation of
      additional staff time and (2) improvements in the effectiveness of mental health
      interventions. Results support the ability of screening to facilitate more rapid
      entry into services and suggest that improving the effectiveness of mental health
      services for students with depression via the implementation of an evidence-based
      treatment protocol may have a limited impact on overall recovery rates and
      service availability. In our example, the SD approach proved useful in informing
      systems' decision-making about the adoption of a new school mental health
      service. 

PMID- 25601194
TI  - Clinical and morphological features of fibronectin glomerulopathy: a report of
      ten patients from a single institution.
AB  - AIMS: Fibronectin glomerulopathy is a rare glomerular disease caused by the
      progressive deposition of fibronectin. We report 10 Chinese patients with
      fibronectin glomerulopathy. METHODS: Renal biopsies were performed on all
      patients, and the clinical and pathological parameters for all patients were
      analyzed. RESULTS: There were 6 males and 4 females, with an average age of 29+/
      8 years. One patient had a family history of renal disease, all patients
      presented with proteinuria, and 80% of them suffered nephrotic range proteinuria.
      No patient demonstrated gross hematuria. The levels of serum creatinine were
      elevated, and the eGFR was decreased in 5 patients. Renal biopsy revealed a
      lobulated glomerular tuft. Patients showed numerous periodic acid-Schiff-positive
      and fuchsinophilic deposits in the mesangial area and along the capillary loops.
      Immense levels of fibronectin were detected in the glomerulus after
      immunofluorescence analysis. An electron microscopy scan found numerous electron
      dense deposits in the mesangial and subendothelial areas. Immune-electron
      microscopy confirmed that the deposits consisted of fibronectin. CONCLUSION:
      Nephrotic proteinuria and massive intraglomerular fibronectin deposits are the
      most significant features of fibronectin glomerulopathy.

PMID- 25601195
TI  - Design and development of a linked open data-based health information
      representation and visualization system: potentials and preliminary evaluation.
AB  - BACKGROUND: Healthcare organizations around the world are challenged by pressures
      to reduce cost, improve coordination and outcome, and provide more with less.
      This requires effective planning and evidence-based practice by generating
      important information from available data. Thus, flexible and user-friendly ways
      to represent, query, and visualize health data becomes increasingly important.
      International organizations such as the World Health Organization (WHO) regularly
      publish vital data on priority health topics that can be utilized for public
      health policy and health service development. However, the data in most portals
      is displayed in either Excel or PDF formats, which makes information discovery
      and reuse difficult. Linked Open Data (LOD)-a new Semantic Web set of best
      practice of standards to publish and link heterogeneous data-can be applied to
      the representation and management of public level health data to alleviate such
      challenges. However, the technologies behind building LOD systems and their
      effectiveness for health data are yet to be assessed. OBJECTIVE: The objective of
      this study is to evaluate whether Linked Data technologies are potential options
      for health information representation, visualization, and retrieval systems
      development and to identify the available tools and methodologies to build Linked
      Data-based health information systems. METHODS: We used the Resource Description
      Framework (RDF) for data representation, Fuseki triple store for data storage,
      and Sgvizler for information visualization. Additionally, we integrated SPARQL
      query interface for interacting with the data. We primarily use the WHO health
      observatory dataset to test the system. All the data were represented using RDF
      and interlinked with other related datasets on the Web of Data using Silk-a link
      discovery framework for Web of Data. A preliminary usability assessment was
      conducted following the System Usability Scale (SUS) method. RESULTS: We
      developed an LOD-based health information representation, querying, and
      visualization system by using Linked Data tools. We imported more than 20,000 HIV
      related data elements on mortality, prevalence, incidence, and related variables,
      which are freely available from the WHO global health observatory database.
      Additionally, we automatically linked 5312 data elements from DBpedia, Bio2RDF,
      and LinkedCT using the Silk framework. The system users can retrieve and
      visualize health information according to their interests. For users who are not
      familiar with SPARQL queries, we integrated a Linked Data search engine interface
      to search and browse the data. We used the system to represent and store the
      data, facilitating flexible queries and different kinds of visualizations. The
      preliminary user evaluation score by public health data managers and users was 82
      on the SUS usability measurement scale. The need to write queries in the
      interface was the main reported difficulty of LOD-based systems to the end user.
      CONCLUSIONS: The system introduced in this article shows that current LOD
      technologies are a promising alternative to represent heterogeneous health data
      in a flexible and reusable manner so that they can serve intelligent queries, and
      ultimately support decision-making. However, the development of advanced text
      based search engines is necessary to increase its usability especially for
      nontechnical users. Further research with large datasets is recommended in the
      future to unfold the potential of Linked Data and Semantic Web for future health
      information systems development.

PMID- 25601196
TI  - A perfectly aligned 63 helical tubular cuprous bromide single crystal for
      selective photo-catalysis, luminescence and sensing of nitro-explosives.
AB  - A perfectly aligned 63 helical tubular cuprous bromide single crystal has been
      synthesized and characterized, which can selectively decompose negatively charged
      dyes of Methyl Orange (MO) and Kermes Red (KR), and the photocatalytic efficiency
      is higher than that of nanosized (~25 nm) TiO2 and ZnO. The direction and
      magnitude of the dipole moments as well as the band structure were calculated to
      reveal high photocatalytic efficiency. Moreover, luminescence studies indicate
      that the CuBr tube materials show very strong yellowish green emissions in the
      solid state and emulsion even at room temperature, and exhibit extremely high
      detection sensitivity towards nitro-explosives via fluorescence quenching.
      Detectable luminescence responses were observed at a very low concentration of 20
      ppm with a high quenching efficiency of 94.90%. The results suggest that they may
      be promising multifunctional materials for photo-catalysis, luminescence and
      sensing of nitro-explosives. 

PMID- 25601197
TI  - Carbon encapsulated iron oxide nanoparticles surface engineered with polyethylene
      glycol-folic acid to induce selective hyperthermia in folate over expressed
      cancer cells.
AB  - Carbon encapsulated iron oxide nanoparticles (CEIO-NPs) prepared by carbon arc
      method were successfully applied for in vitro magnetic hyperthermia. The CEIO-NPs
      were chemically oxidized and surface modified with PEG-FA for selective tumor
      localization in cancer cells that over expresses the folate receptors (FR(+)).
      The size, morphology, heating efficiency, biocompatibility and in vitro cell
      uptake of CEIO-PEG-FA NPs are extensively characterized. The as-prepared
      nanoparticles have generated quick heating (43-45 degrees C) upon exposure to an
      alternating magnetic field (AMF) with the saturation magnetization of 25emu/g.
      The LDH cytotoxic assay demonstrated that the nanoparticle did not affect the
      viability of normal human fibroblast. The quantitative and cellular uptake
      studies by TEM confirmed the selective and increased uptake of CEIO-PEG-FA NPs
      when compared to the CEIO-nanoparticles. In conclusion, CEIO-PEG-FA NPs have the
      potential to induce magnetic hyperthermia in FR(+) cells via the receptor
      mediated endocytosis uptake mechanism. 

PMID- 25601198
TI  - Fabrication of drug-loaded edible carrier substrates from nanosuspensions by
      flexographic printing.
AB  - The main goal of the current work was to investigate the possible use of
      flexographic printing for the conversion of nanosuspensions into solid dosage
      forms. Aqueous nanosuspensions of indomethacin (IND) and itraconazole (ITR) with
      Poloxamer 407 as the stabilizer agent were prepared by wet ball-milling. The
      nanosuspensions were flexographically printed on three different substrates,
      including two commercially available edible substrates. The printed formulations
      were characterized with X-ray diffractometry (XRD) and scanning electron
      microscopy (SEM). In addition, dissolution studies for the printed IND and ITR
      formulations were conducted. The mean particle size of milled nanosuspensions of
      IND and ITR was 422.6 +/- 7.7 nm and 698.1 +/- 14.0 nm, respectively. The SEM
      imaging showed even distribution of nanosuspensions on the substrates after
      printing without any evident agglomeration. The printed formulations contained
      drug at least partially in crystalline form. The drug dissolution rate from the
      prepared formulations was improved compared to the pure drug. The drug release
      from the preparations on edible substrates was slightly slower due to the
      incorporation of the drug particles into the substrate matrix. In conclusion, the
      results indicated that flexographic printing can be considered as a promising
      fabrication method of solid nanoparticulate systems with enhanced dissolution
      behavior.

PMID- 25601199
TI  - Biorelevant media resistant co-culture model mimicking permeability of human
      intestine.
AB  - Cell culture models are currently used to predict absorption pattern of new
      compounds and formulations in the human gastro-intestinal tract (GIT). One major
      drawback is the lack of relevant apical incubation fluids allowing mimicking
      luminal conditions in the GIT. Here, we suggest a culture model compatible with
      biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and
      Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2
      and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability
      and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF
      with co-culture. Influence of biorelevant fluids on paracellular permeability or
      transporter proteins were also evaluated. Results were compared with Caco-2 and
      HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF,
      no toxic effect was detected for the co-cultures in terms of viability and
      lactate dehydrogenase release. The addition of FeSSIF to the basolateral
      compartment of the co-culture induced cytotoxic effects which suggested the
      apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced
      a slight increase of the paracellular transport and both tested media inhibited
      partially the P-gp-mediated efflux in the co-culture. Additionally, the
      absorptive transport of propranolol hydrochloride, a lipophilic beta-blocker, was
      strongly affected by biorelevant fluids. This study demonstrated the
      compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant
      media. Combining biorelevant intestinal fluids with features such as mucus
      secretion, adjustable paracellular and P-gp mediated transports, is a step
      forward to more realistic in-vitro models of the human intestine.

PMID- 25601200
TI  - Antiseptic mouthwashes could worsen xerostomia in patients taking polypharmacy.
AB  - OBJECTIVE: Polypharmacy is a common cause of xerostomia. This study aimed to
      investigate whether xerostomia could be an adverse drug event of mouthwashes,
      when they are used for longer than 2 weeks by patients taking polypharmacy.
      MATERIALS AND METHODS: This cross-sectional observational study included 120
      hospitalized patients (60 middle-aged and 60 elderly patients), taking
      polypharmacy (>=4 drugs daily) and at risk of drug-induced xerostomia. Xerostomia
      was assessed by questioning participants. RESULTS: A total of 62.5% of patients
      complained of xerostomia. In the middle-aged group (mean age=44.0 (8.7) years;
      35.0% women) xerostomia seemed independently associated to mouthwashes, at the
      limit of significance (OR=5.00, 95% CI=0.99-25.3, p=0.052). Active principles in
      mouthwashes were mainly quaternary ammonium compounds (91.9%). Mouthwashes may
      disturb the healthy balance of the biofilm moisturizing the oral mucosa. The
      biofilm contains mucins, salivary glycoproteins with oligosaccharides side chains
      able to sequester water and endogenous bacteria surrounded by a glycocalyx. Oral
      bacteria are fully susceptible to quaternary ammonium (chlorhexidine, hexetidine,
      cetylpyridinium chloride) and to other antiseptics used in mouthwashes, such as
      betain, resorcin, triclosan, essential oils and alcohol. However, caregivers
      currently recommend such dental plaque control products to patients suffering
      from xerostomia in order to reduce the risk of caries and periodontitis.
      CONCLUSION: This study is the first report that use of antiseptic mouthwashes for
      more than 2 weeks could worsen xerostomia in patients taking polypharmacy. Oral
      care protocols should avoid this iatrogenic practice, particularly when
      xerostomia alters the quality-of-life and worsens malnutrition.

PMID- 25601201
TI  - The current use of active surveillance in an Australian cohort of men: a pattern
      of care analysis from the Victorian Prostate Cancer Registry.
AB  - OBJECTIVES: To ascertain the treatment trends and patterns of care, for men with
      prostate cancer on active surveillance (AS) in Victoria, Australia. PATIENTS AND
      METHODS: De-identified data was obtained for 6424 men from the Victorian Prostate
      Cancer Registry. Men included in this study were diagnosed with prostate cancer
      from 2008 to August 2012 with >= 12-months of follow-up. Patients were stratified
      using the National Comprehensive Cancer Network (NCCN) risk grouping system and
      those who were not actively treated were identified. Data was acquired to
      describe the trends and uptake of AS according to public vs private hospital
      sector, and regional vs metropolitan regions. RESULTS: In all, 1603/6424 (24.9%)
      men received no treatment with curative intent at 12-months follow-up. This
      cohort included patients in whom the chosen management plan was recorded as AS
      (980/1603, 61.1%), watchful waiting (341/1603, 21.3%), or no management plan
      (282/1603, 17.6%). From this, 980/6424(15.3%) of the patients were recorded as
      being on AS across all NCCN categories at 12 months after diagnosis. This
      included 653/1816 (35.9%) of very low- and low-risk men, and 251/2820 (8.9%) of
      intermediate-risk men. Of our patients on AS, 169/980 (17.2%) progressed onto
      active treatment after 12 months. This active treatment included radical
      prostatectomy in 116 (68.6%), 32 (18.9%) undergoing external beam radiation
      therapy, 12 (7.1%) undergoingt brachytherapy and nine (5.3%) undergoing androgen
      deprivation therapy. Overall, 629/979 (64.2%) of the AS patients were notified
      from a private hospital, with 350/979 (35.7%) of the patients notified from a
      public hospital (one patient unclassified). Of these, 202/652 (30.9%) of the AS
      patients with very low-/low-risk disease were managed in the public sector, vs
      450/652 (69%) of very low-/low-risk AS patients being managed in the private
      sector. In our cohort, patients with very low- and low-risk disease, managed in a
      private hospital, were more likely to be on AS (P = 0.005). AS patients in the
      private sector were also a median of 2.8 years younger (median 65.6 vs 68.4
      years, P < 0.001); had a lower median PSA level (5.3 vs 6.7 ng/mL, P < 0.001);
      and had lower biopsy Gleason score and clinical staging. There was no significant
      difference in the uptake of AS demographically, in our cohort of men between
      metropolitan and regional areas. CONCLUSION: In this contemporary registry-based
      population, AS is being used in a significant proportion of patients. The
      proportion of men progressing to intervention is lower than that reported in the
      current literature. Patients are more likely to be on AS if they are managed in a
      private hospital, with no differences in the uptake of AS, from metropolitan to
      regional areas.

PMID- 25601202
TI  - Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced
      lifespan in Drosophila fed a lipid-rich diet.
AB  - Long-term consumption of fatty foods is associated with obesity, macrophage
      activation and inflammation, metabolic imbalance, and a reduced lifespan. We took
      advantage of Drosophila genetics to investigate the role of macrophages and the
      pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich
      diet presented with increased fat storage, systemic activation of JAK-STAT
      signaling, reduced insulin sensitivity, hyperglycemia, and a shorter lifespan.
      Drosophila macrophages produced the JAK-STAT-activating cytokine upd3, in a
      scavenger-receptor (crq) and JNK-dependent manner. Genetic depletion of
      macrophages or macrophage-specific silencing of upd3 decreased JAK-STAT
      activation and rescued insulin sensitivity and the lifespan of Drosophila, but
      did not decrease fat storage. NF-kappaB signaling made no contribution to the
      phenotype observed. These results identify an evolutionarily conserved "scavenger
      receptor-JNK-type 1 cytokine" cassette in macrophages, which controls glucose
      metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via
      activation of the JAK-STAT pathway.

PMID- 25601204
TI  - Electrospinning polyelectrolyte complexes: pH-responsive fibers.
AB  - Fibers were electrospun from a solution comprised of oppositely charged
      polyelectrolytes, in efforts to achieve highly confined macromolecular packaging.
      A stoichiometric ratio of poly(allylamine hydrochloride) and poly(acrylic acid)
      solution was mixed in an ethanol-water co-solvent. Differential scanning
      calorimetry (DSC) analysis of electrospun fibers demonstrated no indication of
      glass transition, Tg. Infrared spectroscopy (FTIR) analysis of the fibers as a
      function of temperature, demonstrated an amidation process at lower temperature
      compared to cast film. Polarized FTIR indicated a preference of the functional
      groups to be perpendicular to the fiber axis. These results imply formation of
      mixed phase fibers with enhanced conditions for intermolecular interactions, due
      to the highly aligned and confined assembly of the macromolecules. The tunable
      intermolecular interactions between the functional groups of the
      polyelectrolytes, impact pH-driven, reversible swelling-deswelling of the fibers.
      The degree of ionization of PAA at pH 5.5 and pH 1.8 varied from 85% to 18%,
      correspondingly, causing transformation of ionic interactions to hydrogen bonding
      between the functional groups. The chemical change led to a massive water
      diffusion of 500% by weight and to a marked increase of 400% in fiber diameter,
      at a rate of 0.50 MUm s(-1). These results allow for manipulation and tailoring
      of key fiber properties for tissue engineering, membranes, and artificial muscle
      applications. 

PMID- 25601205
TI  - Endothelial cells control pancreatic cell fate at defined stages through EGFL7
      signaling.
AB  - Although endothelial cells have been shown to affect mouse pancreatic
      development, their precise function in human development remains unclear. Using a
      coculture system containing human embryonic stem cell (hESC)-derived progenitors
      and endothelial cells, we found that endothelial cells play a stage-dependent
      role in pancreatic development, in which they maintain pancreatic progenitor (PP)
      self-renewal and impair further differentiation into hormone-expressing cells.
      The mechanistic studies suggest that the endothelial cells act through the
      secretion of EGFL7. Consistently, endothelial overexpression of EGFL7 in vivo
      using a transgenic mouse model resulted in an increase of PP proliferation rate
      and a decrease of differentiation toward endocrine cells. These studies not only
      identified the role of EGFL7 as the molecular handle involved in the crosstalk
      between endothelium and pancreatic epithelium, but also provide a paradigm for
      using hESC stepwise differentiation to dissect the stage-dependent roles of
      signals controlling organogenesis.

PMID- 25601203
TI  - T cell receptor cross-reactivity between similar foreign and self peptides
      influences naive cell population size and autoimmunity.
AB  - T cell receptor (TCR) cross-reactivity between major histocompatibility complex
      II (MHCII)-binding self and foreign peptides could influence the naive CD4(+) T
      cell repertoire and autoimmunity. We found that nonamer peptides that bind to the
      same MHCII molecule only need to share five amino acids to cross-react on the
      same TCR. This property was biologically relevant because systemic expression of
      a self peptide reduced the size of a naive cell population specific for a related
      foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an
      incompletely deleted naive T cell population specific for a tissue-restricted
      self peptide could be triggered by related microbial peptides to cause
      autoimmunity. Thus, TCR cross-reactivity between similar self and foreign
      peptides can reduce the size of certain foreign peptide-specific T cell
      populations and might allow T cell populations specific for tissue-restricted
      self peptides to cause autoimmunity after infection.

PMID- 25601206
TI  - EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1
      dependent manner.
AB  - Glioblastoma (GBM)-derived tumorigenic stem-like cells (GSCs) may play a key role
      in therapy resistance. Previously, we reported that the mitotic kinase MELK binds
      and phosphorylates the oncogenic transcription factor FOXM1 in GSCs. Here, we
      demonstrate that the catalytic subunit of Polycomb repressive complex 2, EZH2, is
      targeted by the MELK-FOXM1 complex, which in turn promotes resistance to
      radiation in GSCs. Clinically, EZH2 and MELK are coexpressed in GBM and
      significantly induced in postirradiation recurrent tumors whose expression is
      inversely correlated with patient prognosis. Through a gain-and loss-of-function
      study, we show that MELK or FOXM1 contributes to GSC radioresistance by
      regulation of EZH2. We further demonstrate that the MELK-EZH2 axis is
      evolutionarily conserved in Caenorhabditis elegans. Collectively, these data
      suggest that the MELK-FOXM1-EZH2 signaling axis is essential for GSC
      radioresistance and therefore raise the possibility that MELK-FOXM1-driven EZH2
      signaling can serve as a therapeutic target in irradiation-resistant GBM tumors. 

PMID- 25601207
TI  - Nonirradiated NOD,B6.SCID Il2rgamma-/- Kit(W41/W41) (NBSGW) mice support
      multilineage engraftment of human hematopoietic cells.
AB  - In this study, we demonstrate a newly derived mouse model that supports
      engraftment of human hematopoietic stem cells (HSCs) in the absence of
      irradiation. We cross the NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) strain with
      the C57BL/6J-Kit(W-41J)/J (C57BL/6.Kit(W41)) strain and engraft, without
      irradiation, the resulting NBSGW strain with human cord blood CD34+ cells. At 12
      weeks postengraftment in NBSGW mice, we observe human cell chimerism in marrow
      (97% +/- 0.4%), peripheral blood (61% +/- 2%), and spleen (94% +/- 2%) at levels
      observed with irradiation in NSG mice. We also detected a significant number of
      glycophorin-A-positive expressing cells in the developing NBSGW marrow. Further,
      the observed levels of human hematopoietic chimerism mimic those reported for
      both irradiated NSG and NSG-transgenic strains. This mouse model permits HSC
      engraftment while avoiding the complicating hematopoietic, gastrointestinal, and
      neurological side effects associated with irradiation and allows investigators
      without access to radiation to pursue engraftment studies with human HSCs. 

PMID- 25601208
TI  - Disequilibrium of BMP2 levels in the breast stem cell niche launches epithelial
      transformation by overamplifying BMPR1B cell response.
AB  - Understanding the mechanisms of cancer initiation will help to prevent and manage
      the disease. At present, the role of the breast microenvironment in
      transformation remains unknown. As BMP2 and BMP4 are important regulators of stem
      cells and their niches in many tissues, we investigated their function in early
      phases of breast cancer. BMP2 production by tumor microenvironment appeared to be
      specifically upregulated in luminal tumors. Chronic exposure of immature human
      mammary epithelial cells to high BMP2 levels initiated transformation toward a
      luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under
      physiological conditions, BMP2 controlled the maintenance and differentiation of
      early luminal progenitors, while BMP4 acted on stem cells/myoepithelial
      progenitors. Our data also suggest that microenvironment-induced overexpression
      of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the
      breast microenvironment in the initiation of stem cell transformation, thus
      providing insight into the etiology of luminal breast cancer. 

PMID- 25601210
TI  - The genus Machaerium (Fabaceae): taxonomy, phytochemistry, traditional uses and
      biological activities.
AB  - Machaerium, in the family Fabaceae, predominantly is a genus of a Neotropical
      distribution of trees, shrubs, and lianas occurring from southern Mexico to
      Brazil and northern Argentina and as far as South America. Several Machaerium
      species are widely used in traditional medicine and are considered to have
      multiple medicinal properties. This review aims to provide up-to-date and
      comprehensive information on the taxonomy, phytochemistry, traditional uses and
      biological activities of plants in the genus Machaerium. 

PMID- 25601211
TI  - A case of rupioid psoriasis exacerbated by systemic glucocorticosteroids.

PMID- 25601209
TI  - Using an Emic lens to understand how Latino families cope with dementia
      behavioral problems.
AB  - Focus group data collected for a larger project to develop a fotonovela for
      Latino caregivers was used to conduct a meaning-centered thematic analysis in
      order to elicit Latino family caregiver perspectives on how behavior problems
      occurring in the context of dementia are perceived and managed. A sample of 42
      Spanish-speaking Latino caregivers were recruited from organizations affiliated
      with the Alzheimer's Association near San Diego, California. Caregivers were
      queried on challenging behaviors, coping strategies, as well as other daily
      challenges. Focus group sessions were conducted in Spanish, translated and
      transcribed into English, and analyzed using qualitative, grounded
      anthropological methods. In addition to a range of behavior problems, five
      indigenous approaches to managing challenging behaviors were identified:
      acceptance, love, patience, adaptability, and establishing routines of care.
      Additionally, participants identified persistent challenges which deter effective
      coping. These include: issues with providers, problems with family members,
      limited knowledge of resources, emotional distress, and financial strain. To our
      knowledge, this is one of the few qualitative studies to report indigenous coping
      strategies for dementia behavioral problems. These findings have the potential to
      inform culturally-tailored intervention. 

PMID- 25601212
TI  - Strain energy density gradients in bone marrow predict osteoblast and osteoclast
      activity: a finite element study.
AB  - Huiskes et al. hypothesized that mechanical strains sensed by osteocytes residing
      in trabecular bone dictate the magnitude of load-induced bone formation. More
      recently, the mechanical environment in bone marrow has also been implicated in
      bone's response to mechanical stimulation. In this study, we hypothesize that
      trabecular load-induced bone formation can be predicted by mechanical signals
      derived from an integrative uFE model, incorporating a description of both the
      bone and marrow phase. Using the mouse tail loading model in combination with in
      vivo micro-computed tomography (uCT) we tracked load induced changes in the sixth
      caudal vertebrae of C57BL/6 mice to quantify the amount of newly mineralized and
      eroded bone volumes. To identify the mechanical signals responsible for
      adaptation, local morphometric changes were compared to micro-finite element
      (uFE) models of vertebrae prior to loading. The mechanical parameters calculated
      were strain energy density (SED) on trabeculae at bone forming and resorbing
      surfaces, SED in the marrow at the boundary between bone forming and resorbing
      surfaces, along with SED in the trabecular bone and marrow volumes. The gradients
      of each parameter were also calculated. Simple regression analysis showed mean
      SED gradients in the trabecular bone matrix to significantly correlate with newly
      mineralized and eroded bone volumes R(2)=0.57 and 0.41, respectively, p<0.001).
      Nevertheless, SED gradients in the marrow were shown to be the best predictor of
      osteoblastic and osteoclastic activity (R(2)=0.83 and 0.60, respectively,
      p<0.001). These data suggest that the mechanical environment of the bone marrow
      plays a significant role in determining osteoblast and osteoclast activity. 

PMID- 25601213
TI  - Chronic nicotine administration does not alter cognitive or mood associated
      behavioural parameters.
AB  - Nicotine, the major specific alkaloid in tobacco smoke, exhibits widespread
      pharmacological effects and may contribute to deterioration in behaviour. The
      present study thus examined the effects of its chronic administration on some
      cognitive and mood associated behaviours. Adult rats weighing between 150 and
      200g were randomly divided into 4 groups each of 5 females and 5 males. Three
      groups were administered graded doses of nicotine at 0.25, 2 and 4mg/kg body
      weight via subcutaneous injections. One group served as control and received
      normal saline (vehicle for nicotine). Behavioural tests were performed using the
      Y-maze, elevated-plus maze (EPM) and tail suspension tests (TST) at various time
      points. Nicotine produced no significant effect in spontaneous alternation on Y
      maze, nor on six parameters scored on EPM (open arm entries, time spent in open
      arms, time per open arm entries, open/closed arm quotient, closed arm entries,
      and total arm entries), and also no significant effect on immobility time in TST.
      This lack of effects was observed to be independent of sex and dose administered.
      The study shows that nicotine does not produce long-term changes in some
      cognitive and mood associated behaviours, thus suggesting it could be well
      tolerated even following chronic administration. 

PMID- 25601214
TI  - Flexible guided self-determination intervention for younger adults with poorly
      controlled Type 1 diabetes, decreased HbA1c and psychosocial distress in women
      but not in men: a real-life RCT.
AB  - AIM: To report results from an 18-month randomized controlled trial (RCT) testing
      the effectiveness of a flexible guided self-determination (GSD) intervention on
      glycaemic control and psychosocial distress in younger adults with poorly
      controlled Type 1 diabetes. METHODS: Between January 2010 and February 2012, we
      randomly allocated two hundred 18-35-year-olds [mean age 25.7 (5.1) years, 50%
      men] with Type 1 diabetes for >= 1 year [mean duration 13.7 (6.8) years] and
      HbA1c  >= 64 mmol/mol (8.0%) to either an immediate GSD (intervention; n = 134)
      or 18-months delayed GSD group (control; n = 66). Group-based or individual GSD
      sessions were offered, drawing on reflection sheets and advanced professional
      communication. The primary outcome was HbA1c (measured at baseline and every
      three months thereafter) and among secondary outcomes was psychosocial distress
      (self-reported at baseline and after nine and 18 months). Intention-to-treat
      analyses included linear regression and repeated measurement analyses. RESULTS: A
      borderline significant decrease in HbA1c in the intervention group compared with
      the control group ( - 4 vs - 1 mmol/mol or - 0.4% vs - 0.1%; P = 0.073) was
      driven by a significantly greater reduction in the GSD women ( - 5 vs + 1
      mmol/mol or - 0.5% vs + 0.1%; P = 0.017); parallel decreases were observed in the
      GSD and control men ( - 3 mmol/mol or  - 0.3%; P = 0.955). Significantly greater
      reduction in the GSD group's psychosocial distress was again driven by
      differences between the GSD and the control women. The men's improvements were
      not connected with the intervention. CONCLUSIONS: The flexible GSD intervention
      benefitted younger adult women by significantly improving glycaemic control and
      decreasing diabetes related distress. No effect was seen among men.

PMID- 25601215
TI  - High Throughput Screen Identifies Natural Product Inhibitor of Phenylalanyl-tRNA
      Synthetase from Pseudomonas aeruginosa and Streptococcus pneumoniae.
AB  - Pseudomonas aeruginosa and Streptococcus pneumoniae are causative agents in a
      wide range of infections. Genes encoding proteins corresponding to phenylalanyl
      tRNA synthetase (PheRS) were cloned from both bacteria. The two forms of PheRS
      were kinetically evaluated and the K(m)'s for P. aeruginosa PheRS with its three
      substrates, phenylalanine, ATP and tRNA(Phe) were determined to be 48, 200, and
      1.2 uM, respectively, while the K(m)'s for S. pneumoniae PheRS with respect to
      phenylalanine, ATP and tRNA(Phe) were 21, 225 and 0.94 uM, respectively. P.
      aeruginosa and S. pneumoniae PheRS were used to screen a natural compound library
      and a single compound was identified that inhibited the function of both enzymes.
      The compound inhibited P. aeruginosa and S. pneumoniae PheRS with IC50's of 2.3
      and 4.9 uM, respectively. The compound had a K(I) of 0.83 and 0.98 uM against P.
      aeruginosa and S. pneumoniae PheRS, respectively. The minimum inhibitory
      concentration (MIC) of the compound was determined against a panel of Gram
      positive and negative bacteria including efflux pump mutants and hyper-sensitive
      strains. MICs against wild-type P. aeruginosa and S. pneumoniae cells in culture
      were determined to be 16 and 32 ug/ml, respectively. The mechanism of action of
      the compound was determined to be competitive with the amino acid, phenylalanine,
      and uncompetitive with ATP. There was no inhibition of cytoplasmic protein
      synthesis, however, partial inhibition of the human mitochondrial PheRS was
      observed.

PMID- 25601217
TI  - The Power of Positivity: Predictors of Relationship Satisfaction for Parents of
      Children with Autism Spectrum Disorder.
AB  - The current study uses the actor-partner interdependence model to examine the
      predictors of relationship satisfaction for mothers and fathers of children with
      autism spectrum disorder. Sixty-seven couples completed measures of optimism,
      benefit finding, coping strategies, social support, and relationship
      satisfaction. Results indicated that parent's positive strengths predicted better
      personal relationship satisfaction. Moreover, parents' benefit finding, use of
      emotional support, and perceived social support from their partner also predicted
      their partner's relationship satisfaction. The results of this study highlight
      the importance of focusing on positive factors that can enhance relationship
      quality. Implications for the development of parent-focused interventions are
      discussed. 

PMID- 25601216
TI  - Compassionate Parenting as a Key to Satisfaction, Efficacy and Meaning Among
      Mothers of Children with Autism.
AB  - Two studies examine the role of compassionate and self-image parenting goals in
      the experience of mothers of children with autism. In Study 1, a comparison
      sample was included. Study 1 included measures of parenting goals, life
      satisfaction, family life satisfaction, parenting satisfaction, and meaning in
      life. Study 2 incorporated a measure of parenting efficacy. Study 1 showed that
      mothers of children with autism were higher than comparison mothers in
      compassionate parenting goals. In both studies, compassionate parenting predicted
      positive outcomes including higher parenting satisfaction (both studies), family
      life satisfaction, meaning in life (Study 1) and higher parenting efficacy (Study
      2). These studies support the notion that compassionate parenting is a key to
      satisfaction for mothers of children with autism. 

PMID- 25601218
TI  - The Treg/Th17 cell ratio is reduced in the skin lesions of patients with pyoderma
      gangrenosum.

PMID- 25601219
TI  - Measuring social capital through multivariate analyses for the IQ-SC.
AB  - BACKGROUND: Social capital can be viewed as a societal process that works toward
      the common good as well as toward the good of the collective based on trust,
      reciprocity, and solidarity. Our study aimed to present two multivariate
      statistical analyses to examine the formation of latent classes of social capital
      using the IQ-SC and to identify the most important factors in building an
      indicator of individual social capital. FINDINGS: A cross-sectional study was
      conducted in 2009 among working adolescents supported by a Brazilian NGO. The
      sample consisted of 363 individuals, and data were collected using the World Bank
      Questionnaire for measuring social capital. First, the participants were grouped
      by a segmentation analysis using the Two Step Cluster method based on the
      Euclidian distance and the centroid criteria as the criteria for aggregate
      answers. Using specific weights for each item, discriminant analysis was used to
      validate the cluster analysis in an attempt to maximize the variance among the
      groups with respect to the variance within the clusters. "Community
      participation" and "trust in one's neighbors" contributed significantly to the
      development of the model with two distinct discriminant functions (p < 0.001).
      The majority of cases (95.0%) and non-cases (93.1%) were correctly classified by
      discriminant analysis. CONCLUSIONS: The two multivariate analyses (segmentation
      analysis and canonical discriminant analysis), used together, can be considered
      good choices for measuring social capital. Our results indicate that it is
      possible to form three social capital groups (low, medium and high) using the IQ
      SC.

PMID- 25601221
TI  - LEIS and XPS investigation into the growth of cerium and cerium dioxide on
      Cu(111).
AB  - The controlled growth of Ce and CeO2 on Cu(111) was investigated applying low
      energy ion scattering spectroscopy (LEIS) and X-ray photoelectron spectroscopy
      (XPS). Previous LEIS studies on metallic and oxidised cerium deposits using other
      metallic substrates reported serious difficulties related to the neutralization
      of noble gas ions. For this reason, special attention was paid here to reveal
      possible matrix effects for the neutralization ("neutralization effects"), which
      would severely hinder quantitative evaluation of the LEIS data. The adsorption of
      O2 on Cu(111) induced no neutralization effects either with He(+) or Ne(+).
      Similarly, no neutralization effects were identified using He(+) upon the
      deposition of metallic Ce on Cu(111), but it arises for the Ce peak monitored
      with Ne(+). The initial growth of Ce is two dimensional up to ThetaCe ~ 0.5 ML,
      while almost complete coverage of Cu(111) is achieved at ThetaCe = 2 ML.
      CeO2(111) was deposited evaporating Ce in a background of O2 at a sample
      temperature of 523 K. No neutralization effects were observed either with He(+)
      or Ne(+). In harmony with literature data, the growth mode is three dimensional.
      Here it was demonstrated that the continuity of the film, which could be
      efficiently checked by LEIS, is influenced by the applied oxygen pressure in the
      range of 5 * 10(-7)-3 * 10(-6) mbar. At pO2 = 3 * 10(-6) mbar the film was not
      completely closed even at relatively large coverages (16 ML), and a significant
      part of copper atoms were oxidized to Cu(1+). Deposition of CeO2 at pO2 = 5 * 10(
      7) mbar was characterized by a nearly perfect wetting, with metallic copper atoms
      at the interface, and with a slightly more reduced ceria layer. 

PMID- 25601220
TI  - Gene expression profiling of lobular carcinoma in situ reveals candidate
      precursor genes for invasion.
AB  - PURPOSE: Lobular carcinoma in situ (LCIS) is both a risk indicator and non
      obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize
      the transcriptomic features of LCIS and ILC, with a focus on the identification
      of intrinsic molecular subtypes of LCIS and the changes involved in the
      progression from normal breast epithelium to LCIS and ILC. METHODS: Fresh-frozen
      classic LCIS, classic ILC, and normal breast epithelium (N) from women undergoing
      prophylactic or therapeutic mastectomy were prospectively collected, laser
      capture microdissected, and subjected to gene expression profiling using
      Affymetrix HG-U133A 2.0 microarrays. RESULTS: Unsupervised hierarchical
      clustering of 40 LCIS samples identified 2 clusters of LCIS distinguished by 6431
      probe sets (p < 0.001). Genes identifying the clusters included proliferation
      genes and other genes related to cancer canonical pathways such as TGF beta
      signaling, p53 signaling, actin cytoskeleton, apoptosis and Wnt-Signaling
      pathway. A supervised analysis to identify differentially expressed genes (p <
      0.001) between normal epithelium, LCIS, and ILC, using 23 patient-matched
      triplets of N, LCIS, and ILC, identified 169 candidate precursor genes, which
      likely play a role in LCIS progression, including PIK3R1, GOLM1, and GPR137B.
      These potential precursor genes map significantly more frequently to 1q and 16q,
      regions frequently targeted by gene copy number alterations in LCIS and ILC.
      CONCLUSION: Here we demonstrate that classic LCIS is a heterogeneous disease at
      the transcriptomic level and identify potential precursor genes in lobular
      carcinogenesis. Understanding the molecular heterogeneity of LCIS and the
      potential role of these potential precursor genes may help personalize the
      therapy of patients with LCIS.

PMID- 25601222
TI  - A comparison of delirium diagnosis in elderly medical inpatients using the CAM,
      DRS-R98, DSM-IV and DSM-5 criteria.
AB  - BACKGROUND: The recently published DSM-5 criteria for delirium may lead to
      different case identification and rates of delirium than previous
      classifications. The aims of this study are to determine how the new DSM-5
      criteria compare with DSM-IV in identification of delirium in elderly medical
      inpatients and to investigate the agreement between different methods, using CAM,
      DRS-R98, DSM-IV, and DSM-5 criteria. METHODS: Prospective, observational study of
      elderly patients aged 70+ admitted under the acute medical teams in a regional
      general hospital. Each participant was assessed within 3 days of admission using
      the DSM-5, and DSM-IV criteria plus the DRS-R98, and CAM scales. RESULTS: We
      assessed 200 patients [mean age 81.1+/-6.5; 50% female; pre-existing cognitive
      impairment in 63%]. The prevalence rates of delirium for each diagnostic method
      were: 13.0% (n = 26) for DSM-5; 19.5% (n = 39) for DSM-IV; 13.5% (n = 27) for DRS
      R98 and 17.0%, (n = 34) for CAM. Using tetrachoric correlation coefficients the
      agreement between DSM-5 and DSM-IV was statistically significant (rhotetr = 0.64,
      SE = 0.1, p < 0.0001). Similar significant agreement was found between the four
      methods. CONCLUSIONS: DSM-IV is the most inclusive diagnostic method for
      delirium, while DSM-5 is the most restrictive. In addition, these classification
      systems identify different cases of delirium. This could have clinical,
      financial, and research implications. However, both classification systems have
      significant agreement in the identification of the same concept (delirium).
      Clarity of diagnosis is required for classification but also further research
      considering the relevance in predicting outcomes can allow for more detailed
      evaluation of the DSM-5 criteria.

PMID- 25601224
TI  - Interview with Jorge J. Casal.

PMID- 25601223
TI  - From microRNA target validation to therapy: lessons learned from studies on BDNF.
AB  - During the past decade, the identification of microRNA (miR) targets has become
      common laboratory practice, and various strategies are now used to detect
      interactions between miRs and their mRNA targets. However, the current lack of a
      standardized identification process often leads to incomplete and/or conflicting
      results. Here, we review the problems most commonly encountered when verifying
      miR-mRNA interactions, and we propose a workflow for future studies. To
      illustrate the challenges faced when validating a miR target, we discuss studies
      in which the regulation of brain-derived neurotrophic factor by miRs was
      investigated, and we highlight several controversies that emerged from these
      studies. Finally, we discuss the therapeutic use of miR inhibitors, and we
      discuss several questions that should be addressed before proceeding to
      preclinical testing. 

PMID- 25601225
TI  - Visualization of data in radiotherapy using web services for optimization of
      workflow.
AB  - BACKGROUND: Every day a large amount of data is produced within a radiotherapy
      department. Although this data is available in one form or other within the
      centralised systems, it is often not in the form which is of interest to the
      departmental staff. This work presents a flexible browser based reporting and
      visualization system for clinical and scientific use, not currently found in
      commercially available software such as MOSAIQ(TM) or ARIA(TM). Moreover, the
      majority of user merely wish to retrieve data and not record and/or modify data.
      Thus the idea was conceived, to present the user with all relevant information in
      a simple and effective manner in the form of web-services. Due to the widespread
      availability of the internet, most people can master the use of a web-browser.
      Ultimately the aim is to optimize clinical procedures, enhance transparency and
      improve revenue. METHODS: Our working group (BAS) examined many internal
      procedures, to find out whether relevant information suitable for our purposes
      lay therein. After the results were collated, it was necessary to select an
      effective software platform. After a more detailed analysis of all data, it
      became clear that the implementation of web-services was appropriate. In our
      institute several such web-based information services had already been developed
      over the last few years, with which we gained invaluable experience. Moreover, we
      strived for high acceptance amongst staff members. RESULTS: By employing web
      services, we attained high effectiveness, transparency and efficient information
      processing for the user. Furthermore, we achieved an almost maintenance-free and
      low support system. The aim of the project, making web-based information
      available to the user from the departmental system MOSAIQ, physician letter
      system MEDATEC(R) and the central finding server MiraPlus (laboratory, pathology
      and radiology) were implemented without restrictions. CONCLUSION: Due to
      widespread use of web-based technology the training effort was effectively nil,
      since practically every member of staff can master the use of a web-browser.
      Moreover, we have achieved high acceptance amongst staff members and have
      improved our effectiveness resulting in a considerable time saving. The many
      MOSAIQ-specific parts of the system can be readily used by departments which use
      MOSAIQ as the departmental system.

PMID- 25601226
TI  - B-mode and Doppler sonography of the mammary glands in dairy goats for mastitis
      diagnosis.
AB  - This study aimed to evaluate the sonographic characteristics of the udder and
      teats and to determine the Doppler indexes of mammary artery in healthy and
      undergoing subclinical and clinical mastitis goats. Thirty animals among Saanen
      and Alpine Brown goats were arranged in three groups, healthy goats (HG), goats
      with subclinical mastitis (SMG) and goats with clinical mastitis (CMG). Using the
      B-mode, the sonographic characteristics (echotexture and echogenicity) and
      biometry (diameter and area of the udder cistern, diameter and area of the teat
      cistern and thickness of the teat wall) were evaluated. Using Doppler
      ultrasonography, the vascular indexes of the mammary artery were obtained. It was
      observed hyperechogenicity with solid component in the gland cistern when
      comparing animals with clinical mastitis and healthy mammary tissue. Regarding
      the echotexture of the breast tissue, there was heterogeneity in the mammary
      parenchyma on the three groups, for the milk, it was observed homogeneity for
      animals on HG and SMG and heterogeneity for animals on CMG. Grey-scale
      quantitative assessment revealed increase in echogenicity (mean value) for all
      the structures when comparing the three groups. Biometry did not reveal
      statistical difference between groups, for none of the evaluated structures.
      Doppler examination of the mammary artery showed the decrease of end diastolic
      velocity and raise of pulsatility index between groups. The association of B-mode
      and Doppler ultrasonography is useful for the evaluation of the udder of dairy
      goats with mastitis. It is a sensitive and specific method for the study of this
      disease. Doppler mode was unable to establish reliable criteria for diagnosis of
      subclinical mastitis. Moreover, the quantification of echogenicity is a useful
      technique for the evaluation of the milk in animals with mastitis; therefore, it
      is suggested that it can be used as complementary technique for the diagnosis of
      mastitis in goats. 

PMID- 25601227
TI  - Effect of hyaluronic acid on tear film thickness as assessed with ultra-high
      resolution optical coherence tomography.
AB  - PURPOSE: The aim of this study was to assess the effect of a single drop of
      hyaluronic acid on tear film thickness (TFT) in healthy subjects. METHODS:
      Sixteen healthy subjects (eight male/eight female) aged between 20 and 36 years
      were included in this randomized, double-masked placebo-controlled study. One eye
      received a single dose of hyaluronic acid (Olixia pure((r)) ; Croma Pharma,
      Korneuburg, Austria) eye drops, and the fellow eye received physiologic saline
      solution as placebo control. The study eye was chosen randomly. TFT as measured
      with a custom-built Fourier-domain optical coherence tomography (FD-OCT) system
      was the main outcome variable and measured before and every 10 min until 1 hr
      after topical administration. RESULTS: Baseline TFT was 4.8 +/- 0.5 MUm in the
      study eye and 5.0 +/- 0.4 MUm in the control eyes. Hyaluronic acid significantly
      increased TFT (p = 0.008 versus placebo) with a maximum effect 10 min after
      instillation (13.9 +/- 11.9%). Post hoc analysis revealed that an increase in TFT
      was seen until 30 min after administration compared to placebo. Data in the
      placebo group show high reproducibility with an intraclass correlation
      coefficient of 0.93 and a coefficient of variation of 5.4 +/- 3.3%. CONCLUSION:
      The data of this study indicate that hyaluronic acid increases TFT for as long as
      30 min in healthy subjects. In addition, our data provide evidence that our
      custom-built OCT system is capable of measuring residence time of lubricants on
      the ocular surface.

PMID- 25601228
TI  - Detecting neuroimaging biomarkers for schizophrenia: a meta-analysis of
      multivariate pattern recognition studies.
AB  - Multivariate pattern recognition approaches have recently facilitated the search
      for reliable neuroimaging-based biomarkers in psychiatric disorders such as
      schizophrenia. By taking into account the multivariate nature of brain functional
      and structural changes as well as their distributed localization across the whole
      brain, they overcome drawbacks of traditional univariate approaches. To evaluate
      the overall reliability of neuroimaging-based biomarkers, we conducted a
      comprehensive literature search to identify all studies that used multivariate
      pattern recognition to identify patterns of brain alterations that differentiate
      patients with schizophrenia from healthy controls. A bivariate random-effects
      meta-analytic model was implemented to investigate the sensitivity and
      specificity across studies as well as to assess the robustness to potentially
      confounding variables. In the total sample of n=38 studies (1602 patients and
      1637 healthy controls), patients were differentiated from controls with a
      sensitivity of 80.3% (95% CI: 76.7-83.5%) and a specificity of 80.3% (95% CI:
      76.9-83.3%). Analysis of neuroimaging modality indicated higher sensitivity
      (84.46%, 95% CI: 79.9-88.2%) and similar specificity (76.9%, 95% CI: 71.3-81.6%)
      of rsfMRI studies as compared with structural MRI studies (sensitivity: 76.4%,
      95% CI: 71.9-80.4%, specificity of 79.0%, 95% CI: 74.6-82.8%). Moderator analysis
      identified significant effects of age (p=0.029), imaging modality (p=0.019), and
      disease stage (p=0.025) on sensitivity as well as of positive-to-negative symptom
      ratio (p=0.022) and antipsychotic medication (p=0.016) on specificity. Our
      results underline the utility of multivariate pattern recognition approaches for
      the identification of reliable neuroimaging-based biomarkers. Despite the
      clinical heterogeneity of the schizophrenia phenotype, brain functional and
      structural alterations differentiate schizophrenic patients from healthy controls
      with 80% sensitivity and specificity. 

PMID- 25601229
TI  - Enhancement of fear extinction with deep brain stimulation: evidence for medial
      orbitofrontal involvement.
AB  - Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS)
      reduces anxiety, fear, and compulsive symptoms in patients suffering from
      refractory obsessive-compulsive disorder. In a rodent model, DBS-like high
      frequency stimulation of VS can either enhance or impair extinction of
      conditioned fear, depending on the location of electrodes within VS (dorsal vs
      ventral). As striatal DBS activates fibers descending from the cortex, we
      reasoned that the differing effects on extinction may reflect differences in
      cortical sources of fibers passing through dorsal-VS and ventral-VS. In agreement
      with prior anatomical studies, we found that infralimbic (IL) and anterior
      insular (AI) cortices project densely through ventral-VS, the site where DBS
      impaired extinction. Contrary to IL and AI, we found that medial orbitofrontal
      cortex (mOFC) projects densely through dorsal-VS, the site where DBS enhanced
      extinction. Furthermore, pharmacological inactivation of mOFC reduced conditioned
      fear and DBS of dorsal-VS-induced plasticity (pERK) in mOFC neurons. Our results
      support the idea that VS DBS modulates fear extinction by stimulating specific
      fibers descending from mOFC and prefrontal cortices. 

PMID- 25601232
TI  - Assimilation of web-based urgent stroke evaluation: a qualitative study of two
      networks.
AB  - BACKGROUND: Stroke is a leading cause of death and serious, long-term disability
      across the world. Urgent stroke care treatment is time-sensitive and requires a
      stroke-trained neurologist for clinical diagnosis. Rural areas, where
      neurologists and stroke specialists are lacking, have a high incidence of stroke
      related death and disability. By virtually connecting emergency department
      physicians in rural hospitals to regional medical centers for consultations,
      specialized Web-based stroke evaluation systems (telestroke) have helped address
      the challenge of urgent stroke care in underserved communities. However, many
      rural hospitals that have deployed telestroke have not fully assimilated this
      technology. OBJECTIVE: The objective of this study was to explore potential
      sources of variations in the utilization of a Web-based telestroke system for
      urgent stroke evaluation and propose a telestroke assimilation model to improve
      stroke care performance. METHODS: An exploratory, qualitative case study of two
      telestroke networks, each comprising an academic stroke center (hub) and
      connected rural hospitals (spokes), was conducted. Data were collected from 50
      semistructured interviews with 40 stakeholders, telestroke usage logs from 32
      spokes, site visits, published papers, and reports. RESULTS: The two networks
      used identical technology (called Remote Evaluation of Acute isCHemic stroke,
      REACH) and were of similar size and complexity, but showed large variations in
      telestroke assimilation across spokes. Several observed hub- and spoke-related
      characteristics can explain these variations. The hub-related characteristics
      included telestroke institutionalization into stroke care, resources for the
      telestroke program, ongoing support for stroke readiness of spokes, telestroke
      performance monitoring, and continuous telestroke process improvement. The spoke
      related characteristics included managerial telestroke championship, stroke
      center certification, dedicated telestroke coordinator, stroke committee of key
      stakeholders, local neurological expertise, and continuous telestroke process
      improvement. CONCLUSIONS: Rural hospitals can improve their stroke readiness with
      use of telestroke systems. However, they need to integrate the technology into
      their stroke delivery processes. A telestroke assimilation model may improve
      stroke care performance.

PMID- 25601233
TI  - Asymmetric total synthesis of (-)-lundurine B and determination of its absolute
      stereochemistry.
AB  - A total synthesis of the Kopsia tenuis alkaloid (-)-lundurine B has been
      achieved. A quaternary chiral carbon has been created by an asymmetric
      deprotonation using a symmetric spiro cyclohexanone intermediate with a chiral
      lithium amide. The hexacyclic skeleton was sequentially constructed through metal
      mediated reactions. The absolute stereochemistry of intermediate 5 has been
      unambiguously established by X-ray crystallographic analysis. This is the first
      description of the absolute stereochemistry of Kopsia tenuis alkaloids based on
      chemical synthesis. 

PMID- 25601230
TI  - Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in
      Animals with Varied HPA Axis Function.
AB  - Previous work has demonstrated the importance of genetic factors and stress
      sensitive circuits in the development of affective disorders. Anxiety and
      numerous psychological disorders are comorbid with substance abuse, and
      noradrenergic signaling in the bed nucleus of the stria terminalis (BNST) is
      thought to be a source of this convergence. Here, we examined the effects of
      different stressors on behavior and norepinephrine dynamics in the BNST of rat
      strains known to differ in their HPA-axis function. We compared the effects of
      acute morphine dependence and social isolation in non-anxious Sprague Dawley (SD)
      rats, and a depression model, Wistar-Kyoto (WKY) rats. We found a shared
      phenotype in drug-dependent and singly housed SD rats, characterized by slowed
      norepinephrine clearance, decreased autoreceptor function, and elevated anxiety.
      WKY rats exhibited changes in anxiety and autoreceptor function only following
      morphine dependence. To ascertain the influence of LC inhibition on this
      plasticity, we administered the LC-terminal-selective toxin DSP-4 to SD and WKY
      rats. DSP-4-treated SD rats demonstrated a dependence-like phenotype, whereas WKY
      rats were unchanged. Overall, our findings suggest that individuals with varying
      stress susceptibilities have different noradrenergic signaling changes in
      response to stress. These changes may establish conditions that favor stress
      induced reinstatement and increase the risk for addiction. 

PMID- 25601231
TI  - Acquisition of responses to a methamphetamine-associated cue in healthy humans:
      self-report, behavioral, and psychophysiological measures.
AB  - Drug-associated cues elicit conditioned responses in human drug users, and are
      thought to facilitate a drug-seeking behavior. Yet, little is known about how
      these associations are acquired, or about the specificity of the conditioned
      response modalities. In this study, healthy, nondependent volunteers (N=90)
      completed a conditioning paradigm in which they received a moderate dose of
      methamphetamine paired with one stimulus and placebo with another stimulus, each
      on two separate occasions. Their responses to these cues were measured with a
      behavioral preference, self-reported 'liking', emotional reactivity, and
      attentional bias measures, both before and after the conditioning. Following the
      conditioning procedure, subjects exhibited a behavioral preference, positive
      emotional reactivity, and attentional bias toward the methamphetamine-associated
      cue, compared with the placebo stimulus. In addition, subjects who reported
      greater positive subjective drug effects during the conditioning displayed a more
      robust conditioning. This work demonstrates that healthy nondependent volunteers
      readily acquire conditioned responses to neutral stimuli paired with a drug. The
      procedure has significant value to study individual variation in acquisition of
      conditioned responses as a possible risk factor for drug taking, and to study the
      neural basis of conditioned drug responses. 

PMID- 25601234
TI  - Long term reference change value of creatinine in HIV-positive patients with anti
      retroviral therapy: A new tool in clinical practice.
AB  - BACKGROUND: The use of reference change value (RCV) instead of reference interval
      emerged as an alternative approach for longitudinal interpretation of biological
      marker. Follow-up of creatinine variation in HIV-positive adults remains a
      challenge in order to prevent renal complications. OBJECTIVES: To determine the
      long term RCV of creatinine in HIV-positive adults receiving anti-retroviral
      therapy (ART) according to the use of tenofovir or ritonavir. DESIGN AND METHODS:
      Longitudinal study of 24 months that include 124 HIV-positive patients followed
      in HIV outpatient unit. Plasma creatinine was measured at 0, 6, 12 and 24 months
      in order to calculate the RCV. RESULTS: In the whole group, a 24-month RCV of
      creatinine was 22.5%. Whatever the ART, the index of individuality was <0.6.
      Significantly higher RCV of creatinine was observed in patients receiving the
      association tenofovir and ritonavir (28%) compared to the patients receiving i)
      tenofovir without ritonavir (21.9%), ii) no tenofovir but ritonavir (22.2%), and
      iii) no tenofovir and no ritonavir (19.7%). CONCLUSIONS: The low value of index
      of individuality pinpointed that RCV should be used to identify critical change
      in serial creatinine results in HIV-positive adults. RCV of creatinine under ART
      was around 20% but reached 28% in case of association of tenofovir and ritonavir.

PMID- 25601235
TI  - Examining pain, body image, and depressive symptoms in patients with lymphedema
      secondary to breast cancer.
AB  - OBJECTIVE: Depression and reduced quality of life are often reported in patients
      with upper-extremity lymphedema secondary to breast cancer treatment. Little is
      known about how pain and body image influence depression in patients with
      lymphedema. The current study examined the association of pain intensity and body
      integrity beliefs with depressive symptoms and the extent to which body image
      dissatisfaction mediated these associations. METHODS: A cross-sectional sample of
      patients with lymphedema secondary to breast cancer treatment completed self
      report questionnaires of pain, body image, and depressive symptoms. Hierarchical
      regression analyses and tests of mediation were conducted to examine the
      associations among the variables of interest. RESULTS: Pain intensity and body
      integrity beliefs were positively associated with depressive symptoms. Further,
      body image dissatisfaction mediated the relationship between pain and depressive
      symptoms, indicating that higher levels of pain led to higher states of body
      image dissatisfaction, which, in turn, led to greater depressive symptoms. Body
      image dissatisfaction also mediated the relationship between body integrity
      beliefs and depressive symptoms, suggesting that greater body integrity beliefs
      led to higher dissatisfaction with one's body and subsequently to greater
      depressive symptoms. CONCLUSIONS: Our findings provide preliminary evidence that
      pain intensity and body image are important factors in understanding depressive
      symptoms in patients with lymphedema. Clinical implications include screening for
      pain and body image concerns in this population to identify patients who are in
      distress. Counseling interventions targeting body image dissatisfaction can also
      be potentially helpful for patients with lymphedema.

PMID- 25601236
TI  - The Organization of Right Prefrontal Networks Reveals Common Mechanisms of
      Inhibitory Regulation Across Cognitive, Emotional, and Motor Processes.
AB  - Inhibitory control/regulation is critical to adapt behavior in accordance with
      changing environmental circumstances. Dysfunctional inhibitory regulation is
      ubiquitous in neurological and psychiatric populations. These populations exhibit
      dysfunction across psychological domains, including memory/thought,
      emotion/affect, and motor response. Although investigation examining inhibitory
      regulation within a single domain has begun outlining the basic neural mechanisms
      supporting regulation, it is unknown how the neural mechanisms of these domains
      interact. To investigate the organization of inhibitory neural networks within
      and across domains, we used neuroimaging to outline the functional and anatomical
      pathways that comprise inhibitory neural networks regulating cognitive,
      emotional, and motor processes. Networks were defined at the group level using an
      array of analyses to indicate their intrinsic pathway structure, which was
      subsequently assessed to determine how the pathways explained individual
      differences in behavior. Results reveal how neural networks underlying inhibitory
      regulation are organized both within and across domains, and indicate
      overlapping/common neural elements. 

PMID- 25601239
TI  - What is the future of the PhD dissertation?

PMID- 25601240
TI  - Integrating interprofessional collaboration skills into the advanced practice
      registered nurse socialization process.
AB  - The emergence of interprofessional collaboration and practice as a means to
      provide patient-centered care and to decrease the current fragmentation of health
      care services in the 21st century provides a clear and unique opportunity for the
      advanced practice registered nurse (APRN) to assume a key role. For APRNs and
      other health care providers, to participate effectively as team members requires
      an interprofessional mindset. Development of interprofessional skills and
      knowledge for the APRN has been hindered by a silo approach to APRN role
      socialization. The Institute of Medicine Report (IOM; 2010) states that current
      health care systems should focus on team collaboration to deliver accessible,
      high-quality, patient-centered health care that addresses wellness and prevention
      of illness and adverse events, management of chronic illness, and increased
      capacity of all providers on the team. The purpose of this article is to
      demonstrate the need to incorporate interprofessional education (IPE) into the
      socialization models used in advanced practice nursing programs. IPE requires
      moving beyond profession-specific educational efforts to engage students of
      different health care professions in interactive learning. Being able to work
      effectively as member of a clinical team while a student is a fundamental part of
      that learning (Interprofessional Education Collaborative Expert Panel, 2011). The
      objective of IPE curriculum models in graduate nursing programs is to educate
      APRNs in the development of an interprofessional mindset. Interprofessional
      collaboration and coordination are needed to achieve seamless transitions for
      patients between providers, specialties, and health care settings (IOM, 2010).
      Achieving the vision requires the continuous development of interprofessional
      competencies by APRNs as part of the learning process, so that upon entering the
      workforce, APRNs are ready to practice effective teamwork and team-based care.
      Socialization of the professional APRN role must integrate interprofessional
      competencies and interactions to prepare APRNs accordingly. 

PMID- 25601241
TI  - Creating a faculty community that values curricular assessment and improvement:
      one DNP program's experience.
AB  - Developing faculty ownership of ongoing curricular improvement presents
      educational and management challenges for schools of nursing, yet little has been
      published about which components help build a faculty community that values
      curricular assessment and improvement. The purpose of this case study was to
      describe key features of and faculty satisfaction with one school of nursing's
      doctor of nursing practice curricular assessment process, with a description of
      key considerations for developing an ePortfolio-supported curricular assessment
      process. ePortfolio matrices were used as a curricular organizing structure for
      mapping and scoring each completed student assignment to an American Association
      of Colleges of Nursing Essential descriptor using a rubric that measured evidence
      of student learning. Faculty satisfaction with the process was also evaluated.
      First-year results indicated high levels of faculty satisfaction with the
      assessment process. The initial findings led to four actions for curricular
      improvement and agreement to continue the assessment process biannually. The
      curricular assessment was successful in generating faculty satisfaction,
      identifying needed areas to improve the curriculum, and obtaining faculty
      agreement to continue the process. A faculty community supportive of curricular
      assessment is essential to a transformational learning environment that prepares
      future nursing leaders. 

PMID- 25601242
TI  - The simulated hospital environment: a qualitative study applying space industry
      techniques.
AB  - Patterned after the integrated simulation approach utilized in the space
      industry, we report results of an innovative simulation in nursing, a 96-hour
      continuous simulated hospital environment. Training objectives for our study
      emphasized the integrative and critical thinking skills needed by new graduate
      nurses. The purpose of this study was to determine the process for development
      and the experience of participating in a simulated hospital environment. We
      sought to (a) translate space industry-integrated simulation techniques into
      development of a simulated hospital environment and (b) determine the experience
      of participating in an integrated simulation experience among undergraduate (UG)
      and graduate nursing students and nursing faculty. We used a qualitative mixed
      methods design. Data were collected from participant focus groups, debriefing
      sessions, research team field notes, and electronic health record documentation.
      The sample, 72 student focus group participants, consisted of 12 baccalaureate
      level soon-to-graduate students and 60 graduate nurse practitioner students as
      patient actors and providers. Important themes emerged from the project. We were
      able to design a simulated hospital environment that was true to life. Notably,
      student knowledge-practice gap was a major theme of the study, consistent with
      studies of employer concerns of new graduate nurses. 

PMID- 25601243
TI  - The process of adopting and incorporating simulation into undergraduate nursing
      curricula: a grounded theory study.
AB  - The aim of this study is to explain the process of adopting and incorporating
      simulation as a teaching strategy in undergraduate nursing programs, define
      uptake, and discuss potential outcomes. In many countries, simulation is
      increasingly adopted as a common teaching strategy. However, there is a dearth of
      knowledge related to the process of adoption and incorporation. We used an
      interpretive, constructivist approach to grounded theory to guide this research
      study. We conducted the study was in Ontario, Canada, during 2011-2012. Using
      multiple data sources, we informed the development of this theory including in
      depth interviews (n = 43) and a review of key organizational documents, such as
      mission and vision statements (n = 67) from multiple nursing programs (n = 13).
      The adoption and uptake of mid- to high-fidelity simulation equipment is a
      multistep iterative process involving various organizational levels within the
      institution that entails a seven-phase process: (a) securing resources, (b)
      nursing leaders working in tandem, (c) getting it out of the box, (d) learning
      about simulation and its potential for teaching, (e) finding a fit, (f) trialing
      the equipment, and (g) integrating into the curriculum. These findings could
      assist nursing programs in Canada and internationally that wish to adopt or
      further incorporate simulation into their curricula and highlight potential
      organizational and program level outcomes. 

PMID- 25601237
TI  - Reward Motivation Enhances Task Coding in Frontoparietal Cortex.
AB  - Reward motivation often enhances task performance, but the neural mechanisms
      underlying such cognitive enhancement remain unclear. Here, we used a
      multivariate pattern analysis (MVPA) approach to test the hypothesis that
      motivation-related enhancement of cognitive control results from improved
      encoding and representation of task set information. Participants underwent two
      fMRI sessions of cued task switching, the first under baseline conditions, and
      the second with randomly intermixed reward incentive and no-incentive trials.
      Information about the upcoming task could be successfully decoded from cue
      related activation patterns in a set of frontoparietal regions typically
      associated with task control. More critically, MVPA classifiers trained on the
      baseline session had significantly higher decoding accuracy on incentive than non
      incentive trials, with decoding improvement mediating reward-related enhancement
      of behavioral performance. These results strongly support the hypothesis that
      reward motivation enhances cognitive control, by improving the discriminability
      of task-relevant information coded and maintained in frontoparietal brain
      regions. 

PMID- 25601245
TI  - Using partnerships to advance nursing practice and education: the precious prints
      project.
AB  - With the release of the Institute of Medicine's (2011) Future of Nursing report,
      nursing leaders recognized that strong academic-practice partnerships are
      critical to advancing the report's recommendations. Using established principles
      for academic-practice partnerships, a manufacturer, children's hospital, student
      nurses organization, and college of nursing created the Precious Prints Project
      (P(3)) to give families who have experienced the death of a child a sterling
      silver pendant of the child's fingerprint. This article outlines the background,
      implementation, and benefits of the P(3) partnership with the aim of encouraging
      readers to consider how similar programs might be implemented in their
      organizations. To date, the program has given pendants to more than 90 families.
      In addition, nurses and nursing students have been introduced to the provision of
      a tangible keepsake for families experiencing the loss of a child and
      participation in philanthropy and an academic practice partnership. 

PMID- 25601244
TI  - The effects of scenario-based simulation course training on nurses' communication
      competence and self-efficacy: a randomized controlled trial.
AB  - Studies have shown that an underappreciation of the importance of person-centered
      communication and inappropriate communication training could result in
      unsatisfactory communication performance from nurses. There are a large number of
      studies about communication training for nurses, but not so many about
      communication training in early stages of nursing career. The purpose of this
      study is to compare the effect of a traditional course versus scenario-based
      simulation training on nurses' communication competency, communication self
      efficacy, and communication performance in discharge planning Objective
      Structured Clinical Examination (OSCE). A randomized controlled trial was used
      with a pretest and two posttests. The experimental group underwent the scenario
      based simulation course, whereas the control group received the traditional
      course. A convenience sample of 116 nurses with qualifications ranging from N0
      level (novice nurses) to N2 level (competent nurses) in Taiwan's clinical nursing
      ladder system was recruited from a medical center in northern Taiwan. Analysis of
      covariance was used to determine between-subjects effects on communication
      competency and self-efficacy, whereas independent t test and Mann-Whitney U test
      were used to examine between-subjects effects on learner satisfaction and
      discharge planning communication performance. Paired t test was used to determine
      communication self-efficacy. In this study, the nurses and independent raters
      found scenario-based simulation training more effective than traditional
      communication course. However, standardized patients reported no significant
      difference in communication performance between the two groups of nurses. Despite
      that traditional classroom lectures and simulation-based communication training
      could both produce enhanced communication competency and self-efficacy among
      nurses, this study has established that the latter may be better than the former
      in terms of learner satisfaction and communication performance improvement.
      Therefore, introduction of simulation-based training to in-service nursing
      education could enhance nurses' communication performance in clinical practice. 

PMID- 25601246
TI  - Partnership to improve quality care for veterans: the VA Nursing Academy.
AB  - More than 22 million living veterans reside in the United States. In fact,
      understanding military culture and the experiences of these veterans is important
      to their ongoing health care and the unique challenges faced by many. The
      Veterans Affairs (VA) Nursing Academy began in 2007 to fund pilot partnerships
      between schools of nursing and local VA health care facilities to better serve
      our veteran population. Fifteen academic/service partnerships were selected for
      funding between 2007 and 2009 with the goals of expanding faculty and
      professional development, increasing nursing student enrollment, providing
      opportunities for educational and practice innovations, and increasing the
      recruitment and retention of VA nurses. This article details critical components
      of the partnership developed between the Birmingham VA Medical Center and the
      University of Alabama at Birmingham School of Nursing, a VA Nursing Academy
      partnership funded in the 2009 cohort. Site-specific goals of the partnership are
      described along with a discussion of the framework used to develop the Birmingham
      VA Nursing Academy, which includes relationship building, engagement, governance,
      evaluation of outcomes, and sustainability. The logic model developed for the
      partnership is included, and the interim outputs and outcomes of this practice
      academic partnership are detailed, a number of which can be replicated by VAs and
      schools of nursing across the country. 

PMID- 25601247
TI  - Utilizing an interdisciplinary approach to increase student writing abilities in
      doctor of nurse practice programs.
AB  - This article describes the process and initial outcome of an interdisciplinary
      approach to the development of a writing-enriched curriculum in a doctor of
      nursing practice program at a regional institution in the upper Midwest. 

PMID- 25601248
TI  - A comparative analysis of demographic and academic success characteristics of on
      line and on-campus RN-to-BSN students.
AB  - Despite their proliferation, little is known about how registered nurse-to
      bachelor of science in nursing (RN-to-BSN) students enrolled in on-line programs
      compare to those in on-campus programs. This article reports on a comparative
      analysis of 3,802 students (332 on-campus, 3,470 on-line) conducted to better
      understand characteristics and educational outcomes of individuals who select on
      line learning options. Programs were compared for student demographic
      characteristics (gender, race, age, and prior degree status) and outcome
      variables (progression to graduation and time to completion). Students in the on
      line program were significantly older than on-campus students, and significantly
      more Caucasian/White students were in the on-line program. There were no
      significant differences in gender between groups. Among only those students who
      had already graduated, on-campus students took significantly less time to
      graduate than on-line students and had a higher graduation rate. However, the
      rate of program discontinuation was similar in both groups, and most on-line
      students who had not graduated were still progressing in the program.
      Implications of these findings are that students enrolled in an on-line RN-to-BSN
      program specifically designed to provide them with flexible 5-week terms and
      substantive student supports can have similar educational outcomes. 

PMID- 25601249
TI  - Images in emergency medicine. Acute generalized exanthematous pustulosis.

PMID- 25601250
TI  - Trust me, this is the worst "acne" of your life!

PMID- 25601252
TI  - Commentary: Side impact air bags: mitigating risk in the era of the SUV.

PMID- 25601251
TI  - Are we there yet? Early stopping in clinical trials.

PMID- 25601253
TI  - Love.

PMID- 25601254
TI  - We gotta walk that lonesome valley.

PMID- 25601255
TI  - Annals of Emergency Medicine Journal Club. Full of hot air? Do patients with
      large spontaneous pneumothoraces require hospitalization?: answers to the
      September 2014 Journal Club questions.

PMID- 25601256
TI  - Images in emergency medicine. Pemphigus vulgaris.

PMID- 25601257
TI  - Congruency of disposition after emergency department intubation in a regional
      database.

PMID- 25601258
TI  - In reply.

PMID- 25601259
TI  - The elbow extension test remains a useful adjunct to clinical judgment in elbow
      trauma.

PMID- 25601260
TI  - Intravenous cobinamide versus hydroxocobalamin for acute treatment of severe
      cyanide poisoning in a swine (Sus scrofa) model.

PMID- 25601261
TI  - Auscultation without contamination: a solution for stethoscope use with personal
      protective equipment.

PMID- 25601263
TI  - Images in emergency medicine. Extra-axial intracranial hematoma, midline shift,
      and severe intracranial hypertension detected by transcranial color-coded duplex
      sonography.

PMID- 25601262
TI  - In reply.

PMID- 25601264
TI  - Brucellosis, genital campylobacteriosis and other factors affecting calving rate
      of cattle in three states of Northern Nigeria.
AB  - BACKGROUND: Reproductive diseases limit the productivity of cattle worldwide and
      represent an important obstacle to profitable cattle enterprise. In this study,
      herd brucellosis and bovine genital campylobacteriosis (BGC) status, and
      demographic and management variables were determined and related to predicted
      calving rate (PrCR) of cattle herds in Adamawa, Kaduna and Kano states, Nigeria.
      Serum samples, preputial scrapings, questionnaire data, trans-rectal palpation
      and farm records were used from 271 herds. The Rose-Bengal plate test and
      competitive enzyme-linked immunosorbent assay were used for Brucella serology and
      culture and identification from preputial samples for BGC. A herd was classified
      as positive if one or more animals tested positive. The PrCR was determined as
      the number of calvings expected during the previous 6 and next 6 months as a
      percentage of the number of postpubertal heifers and cows in the herd. A
      multilevel linear regression model was used to estimate the herd-level effect of
      Brucella abortus seropositivity, Campylobacter fetus infection and other factors
      on calculated PrCR. RESULTS: The reproductive performance of the cattle herds was
      generally poor: Only 6.5% of the nursing cows were pregnant and 51.1% were non
      pregnant and acyclic; the mean annual PrCR was 51.4%. Brucella abortus and C.
      fetus infection of herds were independently associated with absolute reduction in
      PrCR of 14.9% and 8.4%, respectively. There was also a strong negative
      association between within-herd Brucella seroprevalence and PrCR. Presence of
      small ruminants, animal introduction without quarantine and the presence of
      handling facilities were associated with lower PrCR, whereas larger herd size,
      supplementary feeding, routine mineral supplementation and care during
      parturition were associated with higher PrCR. CONCLUSIONS: Brucellosis and BGC
      may be largely responsible for the poor reproductive performance of indigenous
      Nigerian cattle. Farmer education and measures to improve the fertility of cattle
      herds are suggested.

PMID- 25601265
TI  - Qualitative research methods in renal medicine: an introduction.
AB  - Qualitative methodologies are becoming increasingly widely used in health
      research. However, within some specialties, including renal medicine, qualitative
      approaches remain under-represented in the high-impact factor journals.
      Qualitative research can be undertaken: (i) as a stand-alone research method,
      addressing specific research questions; (ii) as part of a mixed methods approach
      alongside quantitative approaches or (iii) embedded in clinical trials, or during
      the development of complex interventions. The aim of this paper is to introduce
      qualitative research, including the rationale for choosing qualitative
      approaches, and guidance for ensuring quality when undertaking and reporting
      qualitative research. In addition, we introduce types of qualitative data
      (observation, interviews and focus groups) as well as some of the most commonly
      encountered methodological approaches (case studies, ethnography, phenomenology,
      grounded theory, thematic analysis, framework analysis and content analysis). 

PMID- 25601266
TI  - The long-term outcomes of systemic vasculitis.
AB  - Patients with generalized ANCA-associated small vessel vasculitis (AAV) have a
      very poor outcome if the ANCA-associated vasculitis is not diagnosed, evaluated
      and treated properly. The introduction of treatment with immunosuppressive
      therapy has improved patient survival dramatically but with considerable side
      effects. Besides, almost 50% of surviving patients experience a relapse of
      vasculitis. Since 1995, the European Vasculitis Society (EUVAS) has designed and
      conducted several clinical trials on patients with AAV independently of
      pharmaceutical companies. The studies included patients with newly diagnosed AAV
      and were stratified according to renal function and generalized versus more
      localized forms. As the immediate patient survival has improved, the longer term
      outcome has become more important. There are several reports on outcome of
      patients with ANCA-associated vasculitis, but the patient groups were
      heterogeneous regarding diagnosis as well as treatment and follow-up. Therefore,
      EUVAS decided to further evaluate the effect and possible adverse events of the
      original randomized trials. This review presents an overview on long-term follow
      up of patients with ANCA-associated vasculitis, with focus on relapse rate,
      patient and renal survival and development of cardiovascular disease and
      malignancy. 

PMID- 25601267
TI  - Achieving competency in wound care: an innovative training module using the long
      term care setting.
AB  - Structured academic teaching on wound care was developed, based on the long-term
      care (LTC) setting, with the goal of ensuring that postgraduate family medicine
      residents attain competency in assessment and treatment of wounds and pressure
      ulcers (PUs). The curriculum for the 1-month learning module was based on
      clinical practice guidelines for the prevention, assessment, and treatment of PUs
      and wounds. The learning techniques used include a learners' needs assessment, a
      small-group didactic session, interdisciplinary bedside case discussions and a
      toolkit. The curriculum is delivered in four weekly, 90-minute interdisciplinary
      teaching sessions during the mandatory 1-month geriatrics rotation for
      postgraduate family medicine trainees. Competency is evaluated by the end of the
      module by reviewing trainees' documentation of a thorough objective clinical
      wound assessment, diagnosis of underlying cause, significant contributing risk
      factors and proposed treatment plan. This approach can be used to train family
      medicine, hospitalist, and geriatric residents in other acute or LTC teaching
      facilities where there is a prevalence of PUs. 

PMID- 25601268
TI  - Eccentric morphology of jailed side-branch ostium after stent crossover in
      coronary bifurcation lesions: a three-dimensional optical coherence tomographic
      analysis.
AB  - BACKGROUND: Angiographic stenosis of a jailed side-branch ostium is usually
      observed after a single-stent crossover at coronary bifurcation lesions. However,
      the stenosis severity is typically overestimated due to the limited information
      obtained from two-dimensional morphology by angiography. We evaluated the actual
      stenosis of jailed side-branch ostium using three-dimensional (3D) optical
      coherence tomography (OCT). METHODS: Using 3D reconstructions of OCT data, we
      analyzed minimal lumen area (MLA) and eccentricity of the jailed side-branch
      ostium in 41 patients who were treated with single stent crossover at coronary
      bifurcation lesions and subsequently underwent serial OCT follow-up. RESULTS: The
      MLA of jailed side-branch ostium calculated from quantitative coronary
      angiography (QCA) assuming a circular lumen markedly decreased after stent
      implantation (1.73+/-1.22mm(2) pre-intervention to 0.84+/-0.91mm(2) post
      intervention, p<0.001). However, the MLA of jailed side-branch ostium measured at
      post-intervention by 3D-OCT (2.67+/-1.75mm(2)) was significantly larger than that
      measured by QCA (p<0.001). There were no statistically significant changes in MLA
      of jailed side-branch ostium based on 3D-OCT measurements during the follow-up
      (2.35+/-1.50mm(2) at 3-6 months post-intervention; 2.44+/-1.27mm(2) at 1-2 years
      post-intervention, p=0.098). The shapes of the jailed side-branch ostium were
      nearly elliptical (mean eccentricity index: 2.97+/-1.27 post-intervention; 2.79+/
      1.17 at 3-6 months post-intervention; 2.59+/-1.02 at 1-2 years post
      intervention). CONCLUSIONS: Compared to 3D-OCT measurements, QCA measurements
      overestimated the jailed side-branch ostial stenosis after single stent crossover
      due to eccentric morphology from orthogonal projection in coronary angiography.
      Significant changes in the MLA of jailed side-branch ostium by 3D-OCT were not
      observed during the follow-up.

PMID- 25601270
TI  - Deviation from high-entropy configurations in the atomic distributions of a multi
      principal-element alloy.
AB  - The alloy-design strategy of combining multiple elements in near-equimolar ratios
      has shown great potential for producing exceptional engineering materials, often
      known as 'high-entropy alloys'. Understanding the elemental distribution, and,
      thus, the evolution of the configurational entropy during solidification, is
      undertaken in the present study using the Al1.3CoCrCuFeNi model alloy. Here we
      show that, even when the material undergoes elemental segregation, precipitation,
      chemical ordering and spinodal decomposition, a significant amount of disorder
      remains, due to the distributions of multiple elements in the major phases. The
      results suggest that the high-entropy alloy-design strategy may be applied to a
      wide range of complex materials, and should not be limited to the goal of
      creating single-phase solid solutions.

PMID- 25601269
TI  - Simeprevir and sofosbuvir for treatment of chronic hepatitis C infection.
AB  - PURPOSE: Chronic hepatitis C infection affects a large proportion of the world's
      population and can lead to significant morbidity and mortality. The standard of
      care for treatment of hepatitis C infection has been peginterferon and ribavirin,
      with or without a first-generation protease inhibitor. In late 2013 and early
      2014, sofosbuvir and simeprevir obtained regulatory approval, offering the first
      possibility for all-oral treatment regimens. We provide a review of the clinical
      efficacy and safety of sofosbuvir- and simeprevir-containing regimens. METHODS:
      Studies were identified in PubMed using the terms sofosbuvir and simeprevir in
      combination with hepatitis C. Abstracts of additional studies presented at
      professional meetings but not yet published were also reviewed. All Phase 3
      trials published by August 1, 2014, as well as Phase 2 studies for which there
      was not a corresponding Phase 3 trial, were included in the review. FINDINGS:
      Simeprevir was studied with peginterferon and ribavirin in 7 published Phase 3
      trials, with overall efficacy rates of 59% to 100%. Sofosbuvir was studied with
      ribavirin and with or without peginterferon in 6 Phase 3 trials with overall
      efficacy rates of 50% to 93%. Patient groups with lower response rates tended to
      have cirrhosis and be older, men, and previous null responders. Simeprevir and
      sofosbuvir were studied in combination in 1 Phase 2a study with overall efficacy
      of 92%. Additional studies demonstrated the efficacy and safety of sofosbuvir
      regimens in patients before and after liver transplantation. Overall, the
      simeprevir- and sofosbuvir-containing regimens were tolerated better or as well
      as peginterferon and ribavirin regimens, with fatigue, headache, and nausea the
      most common adverse events. IMPLICATIONS: Results from numerous Phase 3 clinical
      trials indicate that sofosbuvir- and simeprevir-containing regimens are highly
      effective and safe for the treatment of chronic hepatitis C infection. The
      approval of these 2 agents has led to a complete overhaul of published
      guidelines, with sofosbuvir- and simeprevir-containing regimens included in
      preferred regimens.

PMID- 25601271
TI  - An epigenetic view of B-cell disorders.
AB  - B-cell development is a multistep process sustained by a highly coordinated
      transcriptional network under the control of a limited set of transcription
      factors. Epigenetic mechanisms, including DNA methylation, histone
      posttranslational modifications and microRNAs act in concert with transcription
      factors to promote lineage commitment, define and sustain cell identity and
      establish heritable cell-type- and stage-specific gene expression profiles.
      Epigenetic modifiers have recently emerged as key regulators of B-cell
      development and activation. Central to B-cell-mediated immunity are germinal
      centers, transient structures formed in secondary lymphoid organs where antigen
      specific B cells undergo intense proliferation, immunoglobulin somatic
      hypermutation and isotype switching, to generate ultimately long-lived memory B
      cells and terminally differentiated plasma cells expressing high-affinity
      antibodies. Deregulation of one or more epigenetic axes represents a common
      feature of several B-cell disorders arising from germinal center B cells,
      including autoimmunity and lymphoma. Moreover, the hijacking of epigenetic
      determinants is central to the ability of the B-lymphotropic Epstein-Barr virus
      (EBV) to establish, via the germinal center reaction, life-long latency and
      occasionally contribute to malignant B-cell transformation. In the light of
      recent findings, this review will discuss the relevance of epigenetic
      deregulation in the pathogenesis of B-cell diseases. Understanding how specific
      epigenetic alterations contribute to the development of lymphomas, autoimmunity
      and EBV-associated disorders is instrumental to develop novel therapeutic
      interventions for the cure of these often fatal pathologies.

PMID- 25601272
TI  - Non-transcriptional regulation of NLRP3 inflammasome signaling by IL-4.
AB  - Th2 cytokine IL-4 has been previously shown to suppress the production of
      proinflammatory cytokines in monocytes. However, the underlying molecular
      mechanism by which IL-4 signaling antagonizes proinflammatory responses is poorly
      characterized. In particular, whether IL-4 can modulate inflammasome signaling
      remains unknown. Here, we provide evidence that IL-4 suppresses NLRP3-dependent
      caspase-1 activation and the subsequent IL-1beta secretion but does not inhibit
      absent in melanoma 2 (AIM2)- or NLRC4 (NOD-like receptor family, CARD domain
      containing 4)-dependent caspase-1 activation in THP-1 and mouse bone marrow
      derived macrophages. Upon lipopolysaccharide (LPS) or LPS/ATP stimulation, IL-4
      markedly inhibited the assembly of NLRP3 inflammasome, including NLRP3-dependent
      ASC (apoptosis-associated speck-like protein containing a caspase recruitment
      domain) oligomerization, NLRP3-ASC interaction and NLRP3 speck-like oligomeric
      structure formation. The negative regulation of NLRP3 inflammasome by IL-4 was
      not due to the impaired mRNA or protein production of NLRP3 and proinflammatory
      cytokines. Supporting this observation, IL-4 attenuated NLRP3 inflammasome
      activation even in reconstituted NLRP3-expressing macrophages in which NLRP3
      expression is not transcriptionally regulated by TLR-NF-kappaB signaling.
      Furthermore, the IL-4-mediated suppression of NLRP3 inflammasome was independent
      of STAT6-dependent transcription and mitochondrial reactive oxygen species (ROS).
      Instead, IL-4 inhibited subcellular redistribution of NLRP3 into mitochondria and
      microtubule polymerization upon NLRP3-activating stimulation. Our results
      collectively suggest that IL-4 could suppress NLRP3 inflammasome activation in a
      transcription-independent manner, thus providing an endogenous regulatory
      machinery to prevent excessive inflammasome activation. 

PMID- 25601273
TI  - A Zap70-dependent feedback circuit is essential for efficient selection of CD4
      lineage thymocytes.
AB  - During positive selection of CD4(+), CD8(+) double positive (DP) thymocytes,
      expression of the tyrosine kinase Zap70 is subject to developmental regulation.
      Signalling downstream of T-cell receptor (TCR) induces Zap70 expression, forming
      a positive feedback circuit. Although previous studies show this circuit is
      required for generation of CD8 lineage cells, it is not known whether selection
      of CD4 T cells also depends on intact developmental regulation of Zap70. To
      address this, we analysed development of Class II-restricted thymocytes in mice
      lacking the Zap70 transcriptional circuitry. Rescue of Zap70 expression in Zap70(
      /-) mice using a tetracycline-inducible Zap70 transgene, that is not subject to
      positive feedback by TCR signalling, restored positive selection of Class-II
      restricted thymocytes. However, in conditions of static Zap70 expression,
      approximately half of selecting thymocytes failed to commit normally to the CD4
      lineage. Instead, cells that failed to develop into CD4 T cells resembled CD8
      lineage precursor DP thymocytes but failed to survive in vivo. Therefore, the
      Zap70 feedback circuit is essential to efficiently mediate the CD4 lineage
      differentiation programme in response to Class II selecting ligands. 

PMID- 25601274
TI  - HPV16 E7 expression in skin induces TSLP secretion, type 2 ILC infiltration and
      atopic dermatitis-like lesions.
AB  - Atopic dermatitis is a common pruritic and inflammatory skin disorder with
      unknown etiology. Most commonly occurring during early childhood, atopic
      dermatitis is associated with eczematous lesions and lichenification, in which
      the epidermis becomes hypertrophied resulting in thickening of the skin. In this
      study, we report an atopic dermatitis-like pathophysiology results in a murine
      model following the expression of the high-risk human papillomavirus (HPV) 16
      oncoprotein E7 in keratinocytes under the keratin 14 promoter. We show that HPV16
      E7 expression in the skin is associated with skin thickening, acanthosis and
      light spongiosis. Locally, HPV16 E7-expressing skin secreted high levels of
      thymic stromal lymphopoietin (TSLP) and contained increased numbers of innate
      lymphoid cells (ILCs). High levels of circulating immunoglobulin E were
      associated with increased susceptibility to skin allergy in a model of cutaneous
      challenge, and to airway bronchiolar inflammation, enhanced airway goblet cell
      metaplasia and mucus production in a model of atopic march. Surprisingly, skin
      pathology occurred independently of T cells and mast cells. Thus, our findings
      suggest that the expression of a single HPV oncogene in the skin can drive the
      onset of atopic dermatitis-like pathology through the induction of TSLP and type
      2 ILC infiltration. 

PMID- 25601277
TI  - Functional loop dynamics of the streptavidin-biotin complex.
AB  - Accelerated molecular dynamics (aMD) simulation is employed to study the
      functional dynamics of the flexible loop(3-4) in the strong-binding streptavidin
      biotin complex system. Conventional molecular (cMD) simulation is also performed
      for comparison. The present study reveals the following important properties of
      the loop dynamics: (1) The transition of loop(3-4) from open to closed state is
      observed in 200 ns aMD simulation. (2) In the absence of biotin binding, the open
      state streptavidin is more stable, which is consistent with experimental
      evidences. The free energy (DeltaG) difference is about 5 kcal/mol between two
      states. But with biotin binding, the closed state is more stable due to
      electrostatic and hydrophobic interactions between the loop(3-4) and biotin. (3)
      The closure of loop(3-4) is concerted to the stable binding of biotin to
      streptavidin. When the loop(3-4) is in its open-state, biotin moves out of the
      binding pocket, indicating that the interactions between the loop(3-4) and biotin
      are essential in trapping biotin in the binding pocket. (4) In the tetrameric
      streptavidin system, the conformational change of the loop(3-4) in each monomer
      is independent of each other. That is, there is no cooperative binding for biotin
      bound to the four subunits of the tetramer.

PMID- 25601275
TI  - NOD mice are functionally deficient in the capacity of cross-presentation.
AB  - Cross-presentation by CD8(+) conventional dendritic cells (cDCs) is involved in
      the maintenance of peripheral tolerance and this process is termed cross
      tolerance. Previous reports showed that non-obese diabetic (NOD) mice have
      reduced number of splenic CD8(+) cDCs compared with non-diabetic strains, and
      that the administration of Flt3L to enhance DC development resulted in reduced
      diabetes incidence. As CD8(+) cDCs are the most efficient antigen cross
      presenting cells, it was assumed that reduced cross-presentation by non
      activated, tolerogenic CD8(+) cDC predisposes to autoimmune diabetogenesis. Here
      we show for the first time that indeed NOD mice have a defect in autoantigen
      cross-presentation capacity. First, we showed that NOD CD8(+) cDCs were less
      sensitive to iatrogenic cytochrome c, which had previously been shown to
      selectively deplete CD8(+) cDCs that functionally cross-present. Second, we found
      that proliferation of islet-specific glucose-6-phosphatase catalytic subunit
      related protein (IGRP)-specific CD8(+) T cells was impaired in NOD compared with
      non-obese diabetes resistant mice after immunization with cell associated
      recombinant fusion protein containing the cognate IGRP peptide. This study,
      therefore, suggests that the reduced number of CD8(+) cDCs in NOD mice, coupled
      with the reduced capacity to cross-present self-antigens, reduces the overall
      capacity to maintain peripheral tolerance in the spontaneous autoimmune type 1
      diabetes mice. 

PMID- 25601278
TI  - Liver hydatidosis: reasoned indications of surgical treatment. Comparison between
      conservative and radical techniques Retrospective study.
AB  - Liver hydatidosis is a focal benign parasitic disease that still cause high rate
      of morbidity particularly in the Mediterranean area. A retrospective study
      comparing conservative and radical techniques in a General and Urgent Surgery
      operative unit was carried out in order to find signs of its surgical treatment.
      A total of 50 patients, 24 men and 26 women, who experienced a surgical treatment
      from 2000 to 2011, participated, and through the Fisher's Exact Test
      characteristics of the cysts, post-operative complications and relapse were
      compared. As a result, 29 patients undertook conservative surgery, while 21
      radical surgery. There was a relationship between characteristics of the cysts
      and the technique chosen, (p<0.001). Likewise, whenever the diameter was smaller
      than 10cm or localized in the left lobe a radical technique was used. Conversely,
      a conservative technique was used when the diameter was bigger than 10 cm or they
      were localized in the right lobe or complicated by intra-biliary or intra
      peritoneal rupture as well as in contiguity with major vascular and biliary
      structures. In this regard, while the post-operative morbidity was related to the
      conservative techniques (p<0.004), the relapses tended to not be related to any
      techniques in our case (p<0.14). In conclusion, in a non hepato-bilio-pancreatic
      center a radical surgery including liver resection is suggested for left lobe's
      cysts, while a conservative technique tends to be more effective for right lobe's
      cysts mainly if complex. Consequently, patients with complicated presentation
      could explain why conservative treatment causes higher rate of morbidity.

PMID- 25601276
TI  - The deubiquitinating enzyme CYLD regulates the differentiation and maturation of
      thymic medullary epithelial cells.
AB  - The cross talk between thymocytes and the thymic epithelium is critical for T
      cell development and the establishment of central tolerance. Medullary thymic
      epithelial cells (mTECs) are located in the thymic medulla and mediate the
      elimination of self-reactive thymocytes, thereby preventing the onset of
      autoimmunity. Previous studies identified the deubiquitinating enzyme CYLD as a
      critical regulator of T-cell development by activating proximal T-cell receptor
      signaling during the transition of double-positive to single-positive thymocytes.
      Here we evaluated the impact of the naturally occurring short-splice variant of
      the cyld gene (sCYLD) on the development and maturation of mTECs. We found that
      thymi of CYLD(ex7/8) mice, solely expressing sCYLD, displayed a reduced number of
      mature mTECs caused by a developmental block during the transition of immature to
      mature mTECs. Further, we could demonstrate an impaired negative selection of
      thymocytes in these mice. Our data demonstrate that inefficient negative
      selection in the thymus of CYLD(ex7/8) mice result from a defect in mTEC
      maturation. 

PMID- 25601280
TI  - Laparoscopic retroperitoneal radical nephrectomy in a pregnant woman with
      retrocaval artery.

PMID- 25601279
TI  - A mixed methods study of patient-provider communication about opioid analgesics.
AB  - OBJECTIVE: To describe patient-provider communication about opioid pain medicine
      and explore how these discussions affect provider attitudes toward patients.
      METHODS: We audio-recorded 45 HIV providers and 423 patients in routine
      outpatient encounters at four sites across the country. Providers completed post
      visit questionnaires assessing their attitudes toward patients. We identified
      discussions about opioid pain management and analyzed them qualitatively. We used
      logistic regression to assess the association between opioid discussion and
      providers' attitudes toward patients. RESULTS: 48 encounters (11% of the total
      sample) contained substantive discussion of opioid-related pain management. Most
      conversations were initiated by patients (n=28, 58%) and ended by the providers
      (n=36, 75%). Twelve encounters (25%) contained dialog suggesting a difference of
      opinion or conflict. Providers more often agreed than disagreed to give the
      prescription (50% vs. 23%), sometimes reluctantly; in 27% (n=13) of encounters,
      no decision was made. Fewer than half of providers (n=20, 42%) acknowledged the
      patient's experience of pain. Providers had a lower odds of positive regard for
      the patient (adjusted OR=0.51, 95% CI: 0.27-0.95) when opioids were discussed.
      CONCLUSIONS: Pain management discussions are common in routine outpatient HIV
      encounters and providers may regard patients less favorably if opioids are
      discussed during visits. The sometimes-adversarial nature of these discussions
      may negatively affect provider attitudes toward patients. PRACTICE IMPLICATIONS:
      Empathy and pain acknowledgment are tools that clinicians can use to facilitate
      productive discussions of pain management.

PMID- 25601281
TI  - Air exchange rates and migration of VOCs in basements and residences.
AB  - Basements can influence indoor air quality by affecting air exchange rates (AERs)
      and by the presence of emission sources of volatile organic compounds (VOCs) and
      other pollutants. We characterized VOC levels, AERs, and interzonal flows between
      basements and occupied spaces in 74 residences in Detroit, Michigan. Flows were
      measured using a steady-state multitracer system, and 7-day VOC measurements were
      collected using passive samplers in both living areas and basements. A walk
      through survey/inspection was conducted in each residence. AERs in residences and
      basements averaged 0.51 and 1.52/h, respectively, and had strong and opposite
      seasonal trends, for example, AERs were highest in residences during the summer,
      and highest in basements during the winter. Airflows from basements to occupied
      spaces also varied seasonally. VOC concentration distributions were right-skewed,
      for example, 90th percentile benzene, toluene, naphthalene, and limonene
      concentrations were 4.0, 19.1, 20.3, and 51.0 MUg/m(3), respectively; maximum
      concentrations were 54, 888, 1117, and 134 MUg/m(3). Identified VOC sources in
      basements included solvents, household cleaners, air fresheners, smoking, and
      gasoline-powered equipment. The number and type of potential VOC sources found in
      basements are significant and problematic, and may warrant advisories regarding
      the storage and use of potentially strong VOCs sources in basements. PRACTICAL
      IMPLICATIONS: Few IAQ studies have examined basements. A sizable volume of air
      can flow between the basement and living area, and AERs in these two zones can
      differ considerably. In many residences, the basement contains significant
      emission sources and contributes a large fraction of VOC concentrations found in
      the living area. Exposures can be lowered by removing VOC sources from the
      basement; other exposure management options, such as local ventilation or
      isolation, are unlikely to be practical.

PMID- 25601282
TI  - Expression of cholecystokinin2-receptor in rat and human L cells and the
      stimulation of glucagon-like peptide-1 secretion by gastrin treatment.
AB  - Gastrin is a gastrointestinal hormone secreted by G cells. Hypergastrinemia can
      improve blood glucose and glycosylated hemoglobin levels. These positive effects
      are primarily due to the trophic effects of gastrin on beta-cells. In recent
      years, many receptors that regulate secretion of glucagon-like peptide 1 (GLP-1)
      have been identified in enteroendocrine L cell lines. This led us to hypothesize
      that, in addition to the trophic effects of gastrin on beta-cells, L cells also
      express cholecystokinin2-receptor (CCK2R), which may regulate GLP-1 secretion and
      have synergistic effects on glucose homeostasis. Our research provides a
      preliminary analysis of CCK2R expression and the stimulating effect of gastrin
      treatment on GLP-1 secretion in a human endocrine L cell line, using RT-PCR,
      Western blot, immunocytochemistry, and ELISA analyses. The expression of
      proglucagon and prohormone convertase 3, which regulate GLP-1 biosynthesis, were
      also analyzed by real-time PCR. Double immunofluorescence labeling was utilized
      to assess the intracellular localization of CCK2R and GLP-1 in L cells harvested
      from rat colon tissue. Our results showed that CCK2R was expressed in both the
      human L cell line and the rat L cells. We also showed that treatment with
      gastrin, a CCK2R agonist, stimulated the secretion of GLP-1, and that this effect
      was likely due to increased expression of proglucagon and PCSK1 (also known as
      prohormone convertase 3 (PC3 gene)). These results not only provide a basis for
      the role gastrin may play in intestinal L cells, and may also provide the basis
      for the development of a method of gastrin-mediated glycemic regulation. 

PMID- 25601283
TI  - Nasal Eosinophilic Angiocentric Fibrosis with Orbital Extension.
AB  - Eosinophilic angiocentric fibrosis (EAF) is an extremely rare, chronic, benign,
      idiopathic disorder that mostly affects the upper respiratory tract, particularly
      the nasal cavity, and features progressive submucosal perivascular fibrosis. To
      the best of our knowledge, only seven cases of EAF with orbital involvement have
      been reported. We report a case of sinonasal EAF with orbital extension that
      presented with left nasolacrimal duct obstruction. A 35-year-old man presented
      with left epiphora, proptosis, anterolateral globe displacement and nasal
      obstruction. Endoscopic sinus examination showed a firm, gritty, creamy, yellow,
      fibrous, adherent mass of maxillary sinus. Diagnosis was established with
      histopathological examination of excisional biopsy of the lesion. Although EAF is
      very rare, it should be considered in the differential diagnosis of lesions of
      upper airway tract, particularly the nasal cavity. Biopsy is necessary for
      diagnosis and treatment planning. Resecting of the involved tissues completely is
      essential for prevention of recurrence.

PMID- 25601284
TI  - Simultaneous impairment of mitochondrial fission and fusion reduces mitophagy and
      shortens replicative lifespan.
AB  - Aging of biological systems is accompanied by degeneration of mitochondrial
      functions. Different pathways are active to counteract the processes which lead
      to mitochondrial dysfunction. Mitochondrial dynamics, the fission and fusion of
      mitochondria, is one of these quality control pathways. Mitophagy, the controlled
      degradation of mitochondria, is another one. Here we show that these pathways are
      linked. A double deletion mutant of Saccharomyces cerevisiae in which two
      essential components of the fission and fusion machinery, Dnm1 and Mgm1, are
      simultaneously ablated, contain wild-type like filamentous mitochondria, but are
      characterized by impaired respiration, an increased sensitivity to different
      stressors, increased mitochondrial protein carbonylation, and a decrease in
      mitophagy and replicative lifespan. These data show that a balanced mitochondrial
      dynamics and not a filamentous mitochondrial morphotype per se is the key for a
      long lifespan and demonstrate a cross-talk between two different mitochondrial
      quality control pathways. 

PMID- 25601286
TI  - A comparison of energy flow in micelle and vesicle structures.
AB  - We have investigated the vibrational population relaxation dynamics and state
      dependent orientational relaxation behavior of perylene in micelles and vesicles
      formed using the same amphiphile(s). Decanoic acid and its conjugate base sodium
      decanoate can form either micelle or vesicle structures in aqueous solution
      depending on amphiphile concentration and solution pH. The issue of interest in
      this work is whether or not different assemblies of a given amphiphile manifest
      different efficiencies with the dissipation of energy. Vibrational population
      relaxation data show that initial energy flow from the chromophore to the
      amphiphile aliphatic chains is more efficient in micelles than in vesicles.
      Longer time scale relaxation, gauged by transient local heating induced by the
      dissipation of excess energy from perylene shows that the local environment
      formed by micelles experiences greater temperature change than the local
      environment formed by vesicles. This finding suggests that the strength of
      coupling between the bath and the amphiphiles differs for the two structural
      motifs. 

PMID- 25601285
TI  - The H3Africa policy framework: negotiating fairness in genomics.
AB  - Human Heredity and Health in Africa (H3Africa) research seeks to promote fair
      collaboration between scientists in Africa and those from elsewhere. Here, we
      outline how concerns over inequality and exploitation led to a policy framework
      that places a firm focus on African leadership and capacity building as guiding
      principles for African genomics research. 

PMID- 25601287
TI  - Gut microbial metabolism and colon cancer: can manipulations of the microbiota be
      useful in the management of gastrointestinal health?
AB  - The gut microbiota is an important component of the human body and its immune
      modulating and metabolic activities are critical to maintain good health. Gut
      microbes, however, are sensitive to changes in diet, exposure to antibiotics, or
      infections, all of which cause transient disruptions in the microbial
      composition, a phenomenon known as dysbiosis. It is now recognized that microbial
      dysbiosis is at the root of many gastrointestinal disorders. However, the
      mechanisms through which bacterial dysbiosis initiates disease are not fully
      understood. Microbially-derived metabolites and their role in disease have also
      attracted significant attention. Identification of cancer-associated bacteria and
      understanding the contributions of microbial metabolism in health and disease are
      exciting but challenging areas that will allow defining microbial biomarkers for
      predicting gastrointestinal disorders. Understanding the complex interactions
      between gut microbiota, diet, host immune system and host genetics will be
      critical to developing more personalized therapies and approaches to treat
      disease. 

PMID- 25601288
TI  - Exploring structural uncertainty in model-based economic evaluations.
AB  - Given the inherent uncertainty in estimates produced by decision analytic models,
      the assessment of uncertainty in model-based evaluations is an essential part of
      the decision-making process. Although the impact of uncertainty around the choice
      of model structure and making incorrect structural assumptions on model
      predictions is noted, relatively little attention has been paid to characterising
      this type of uncertainty in guidelines developed by national funding bodies such
      as the Australian Pharmaceutical Benefits Advisory Committee (PBAC). The absence
      of a detailed description and evaluation of structural uncertainty can add
      further uncertainty to the decision-making process, with potential impact on the
      quality of funding decisions. This paper provides a summary of key elements of
      structural uncertainty describing why it matters and how it could be
      characterised. Five alternative approaches to characterising structural
      uncertainty are discussed, including scenario analysis, model selection, model
      averaging, parameterization and discrepancy. We argue that the potential effect
      of structural uncertainty on model predictions should be considered in
      submissions to national funding bodies; however, the characterisation of
      structural uncertainty is not well defined within the guidelines of these bodies.
      There has been little consideration of the forms of structural sensitivity
      analysis that might best inform applied decision-making processes, and empirical
      research in this area is required. 

PMID- 25601290
TI  - Metabolic bacterial genes and the construction of high-level composite lineages
      of life.
AB  - Understanding how major organismal lineages originated is fundamental for
      understanding processes by which life evolved. Major evolutionary transitions,
      like eukaryogenesis, merging genetic material from distantly related organisms,
      are rare events, hence difficult ones to explain causally. If most archaeal
      lineages emerged after massive acquisitions of bacterial genes, a rule however
      arises: metabolic bacterial genes contributed to all major evolutionary
      transitions. 

PMID- 25601291
TI  - Psychotropic dose equivalence in Japan.
AB  - Psychotropic dose equivalence is an important concept when estimating the
      approximate psychotropic doses patients receive, and deciding on the approximate
      titration dose when switching from one psychotropic agent to another. It is also
      useful from a research viewpoint when defining and extracting specific subgroups
      of subjects. Unification of various agents into a single standard agent
      facilitates easier analytical comparisons. On the basis of differences in
      psychopharmacological prescription features, those of available psychotropic
      agents and their approved doses, and racial differences between Japan and other
      countries, psychotropic dose equivalency tables designed specifically for
      Japanese patients have been widely used in Japan since 1998. Here we introduce
      dose equivalency tables for: (i) antipsychotics; (ii) antiparkinsonian agents;
      (iii) antidepressants; and (iv) anxiolytics, sedatives and hypnotics available in
      Japan. Equivalent doses for the therapeutic effects of individual psychotropic
      compounds were determined principally on the basis of randomized controlled
      trials conducted in Japan and consensus among dose equivalency tables reported
      previously by psychopharmacological experts. As these tables are intended to
      merely suggest approximate standard values, physicians should use them with
      discretion. Updated information of psychotropic dose equivalence in Japan is
      available at http://www.jsprs.org/en/equivalence.tables/. [Correction added on 8
      July 2015, after first online publication: A link to the updated information has
      been added.]. 

PMID- 25601292
TI  - Three-dimensional morphological modelling of concrete using multiscale Poisson
      polyhedra.
AB  - This paper aims at developing a random morphological model for concrete
      microstructures. A 3D image of concrete is obtained by microtomography and is
      used in conjunction with the concrete formulation to build and validate the model
      through morphological measurements. The morphological model is made up of two
      phases, corresponding to the matrix, or cement paste and to the aggregates. The
      set of aggregates in the sample is modelled as a combination of Poisson polyhedra
      of different scales. An algorithm is introduced to generate polyhedra packings in
      the continuum space. The latter is validated with morphological measurements. 

PMID- 25601293
TI  - Liver-specific Fas silencing prevents galactosamine/lipopolysaccharide-induced
      liver injury.
AB  - Acute liver failure (ALF) is a life threatening disease for which only few
      treatment options exist. The molecular pathways of disease progression are not
      well defined, but the death receptor Fas (CD95/Apo-1) appears to play a pivotal
      role in hepatocyte cell death and the development of ALF. Here, we explored
      posttranscriptional gene silencing of Fas by RNAi to inhibit pathophysiological
      gene expression. For targeting Fas expression in mice, Fas siRNA was formulated
      with the liver-specific siRNA delivery system DBTC. Treatment of mice with
      DBTC/siRNA(Fas) reduced Fas expression in the liver, but not in the spleen, lung,
      kidney or heart. Furthermore, silencing of Fas receptor was effective in blocking
      or reducing several aspects of ALF when it was tested in mice exposed to
      galactosamine/lipopolysaccharide (G/L), a well-known model of ALF. The
      application of DBTC/siRNA(Fas) 48 h prior G/L exposure resulted in amelioration
      of hepatic perfusion, reduction of hepatocellular death and increase of survival
      rate. The administration of DBTC/siRNA(Fas) formulation further diminished the
      inflammatory response upon G/L challenge, as indicated by a marked decrease of
      TNFalpha mRNA expression. However, IL-6 plasma concentration remained
      unaffectedly by DBTC/siRNA(Fas) formulation. Since the specific silencing of
      hepatic Fas expression only partially protected from inflammation, but completely
      attenuated apoptotic and necrotic cell death as well as microcirculatory
      dysfunction, the development of therapeutic strategies with DBTC lipoplex
      formulations to treat ALF should be combined with anti-inflammatory strategies to
      reach maximal therapeutic efficacy. 

PMID- 25601294
TI  - Exposure treatment in multiple contexts attenuates return of fear via renewal in
      high spider fearful individuals.
AB  - BACKGROUND AND OBJECTIVES: Research has demonstrated that after exposure
      treatment, re-exposure to a previously feared stimulus outside of the treatment
      context can result in renewal of fear. The current study investigated whether
      conducting exposure treatment in multiple real-life contexts can attenuate
      renewal of fear. METHODS: Forty-six moderate to high spider fearful individuals
      were randomly allocated to groups that received exposure treatment in either one
      context or three contexts. Follow-up testing was conducted one week and four
      weeks after exposure in the treatment context or a novel context. RESULTS:
      Renewal of fear was found for the single extinction context group when exposed to
      the feared object in a novel context with self-report of fear, heart rate, and
      behavioural avoidance. However, renewal of fear was attenuated for the multiple
      extinction context group. LIMITATIONS: The sample included moderate to high
      spider fearful participants rather than clients with spider phobia, potentially
      limiting the generalisability of the findings to clinical populations.
      CONCLUSIONS: Using multiple extinction contexts in combination with other methods
      of attenuating renewal (e.g., context similarity) may provide a means to reduce
      the risk of renewal of fear.

PMID- 25601295
TI  - LukS-PV, a component of Panton-Valentine leukocidin, exerts potent activity
      against acute myeloid leukemia in vitro and in vivo.
AB  - LukS-PV, a component of Panton-Valentine leukocidin (PVL) secreted by
      Staphylococcus aureus, has been shown to inhibit proliferation and induce
      apoptosis in acute myeloid leukemia (AML) THP-1 cells. Here we investigated anti
      leukemia activities of LukS-PV in HL-60 cells, using in vitro assays to assess
      the ability of LukS-PV to mediate cell viability, apoptosis and differentiation;
      and developing a Severe Combined Immunodeficiency (SCID) mouse model of
      disseminated AML with the HL-60 cells to examine in vivo anti-leukemia activity.
      LukS-PV inhibited viability and induced differentiation and apoptosis in the HL
      60 AML cell line. In the SCID mice, LukS-PV potently inhibited tumor growth,
      decreased tumor cell infiltration into peripheral blood and tissues, and
      significantly increased mean survival time. No severe adverse effects, such as
      death, weight loss, or pathological changes in livers or spleens were observed in
      the toxicity test group. These results indicate that LukS-PV may be a novel and
      effective chemotherapeutic agent against AML. 

PMID- 25601296
TI  - CohortExplorer: A Generic Application Programming Interface for Entity Attribute
      Value Database Schemas.
AB  - BACKGROUND: Most electronic data capture (EDC) and electronic data management
      (EDM) systems developed to collect and store clinical data from participants
      recruited into studies are based on generic entity-attribute-value (EAV) database
      schemas which enable rapid and flexible deployment in a range of study designs.
      The drawback to such schemas is that they are cumbersome to query with structured
      query language (SQL). The problem increases when researchers involved in multiple
      studies use multiple electronic data capture and management systems each with
      variation on the EAV schema. OBJECTIVE: The aim of this study is to develop a
      generic application which allows easy and rapid exploration of data and metadata
      stored under EAV schemas that are organized into a survey format
      (questionnaires/events, questions, values), in other words, the Clinical Data
      Interchange Standards Consortium (CDISC) Observational Data Model (ODM). METHODS:
      CohortExplorer is written in Perl programming language and uses the concept of
      SQL abstract which allows the SQL query to be treated like a hash (key-value
      pairs). RESULTS: We have developed a tool, CohortExplorer, which once configured
      for a EAV system will "plug-n-play" with EAV schemas, enabling the easy
      construction of complex queries through an abstracted interface. To demonstrate
      the utility of the CohortExplorer system, we show how it can be used with the
      popular EAV based frameworks; Opal (OBiBa) and REDCap. CONCLUSIONS: The
      application is available under a GPL-3+ license at the CPAN website. Currently
      the application only provides datasource application programming interfaces
      (APIs) for Opal and REDCap. In the future the application will be available with
      datasource APIs for all major electronic data capture and management systems such
      as OpenClinica and LabKey. At present the application is only compatible with EAV
      systems where the metadata is organized into surveys, questionnaires and events.
      Further work is needed to make the application compatible with EAV schemas where
      the metadata is organized into hierarchies such as Informatics for Integrating
      Biology & the Bedside (i2b2). A video tutorial demonstrating the application
      setup, datasource configuration, and search features is available on YouTube. The
      application source code is available at the GitHub website and the users are
      encouraged to suggest new features and contribute to the development of APIs for
      new EAV systems.

PMID- 25601297
TI  - Six Zn(II) and Cd(II) coordination polymers assembled from a similar binuclear
      building unit: tunable structures and luminescence properties.
AB  - Six Zn(ii) and Cd(ii) coordination polymers were constructed by treating a 2
      substituted 8-hydroxyquinolinate ligand containing a pyridyl group with zinc or
      cadmium salts, and characterized by a variety of techniques. Interestingly, based
      on a similar binuclear Zn(ii) or Cd(ii) building unit, the supramolecular
      structures of the six coordination polymers () exhibit an unprecedented
      structural diversification due to the different choices of metal salts. and
      represent a novel 2D framework containing 1D infinite right- and left-handed
      helical chains. and are 2D coordination frameworks based on binuclear Cd(ii)
      building units. For and , the L ligands can bridge binuclear building units
      forming a 1D infinite chain. Interestingly, the adjacent Cd2O2 planes of the 1D
      chain in are in parallel with each other, while the dihedral angle between the
      two Zn2O2 planes in is 83.43 degrees . Photoluminescence properties revealed that
      the six coordination polymers exhibit redshifted emission maximum compared with
      the free ligand HL, which can be ascribed to an increased conformational rigidity
      and the fabrication of coplanar binuclear building units M2L2 in . Coordination
      polymers also display distinct fluorescence lifetimes and quantum yields because
      of their different metal centers and supramolecular structures. 

PMID- 25601298
TI  - Considering optogenetic stimulation for cochlear implants.
AB  - Electrical cochlear implants are by far the most successful neuroprostheses and
      have been implanted in over 300,000 people worldwide. Cochlear implants enable
      open speech comprehension in most patients but are limited in providing music
      appreciation and speech understanding in noisy environments. This is generally
      considered to be due to low frequency resolution as a consequence of wide current
      spread from stimulation contacts. Accordingly, the number of independently usable
      stimulation channels is limited to less than a dozen. As light can be
      conveniently focused, optical stimulation might provide an alternative approach
      to cochlear implants with increased number of independent stimulation channels.
      Here, we focus on summarizing recent work on optogenetic stimulation as one way
      to develop optical cochlear implants. We conclude that proof of principle has
      been presented for optogenetic stimulation of the cochlea and central auditory
      neurons in rodents as well as for the technical realization of flexible MULED
      based multichannel cochlear implants. Still, much remains to be done in order to
      advance the technique for auditory research and even more for eventual clinical
      translation. This article is part of a Special Issue entitled <Lasker Award>. 

PMID- 25601299
TI  - Dietary treatment of irritable bowel syndrome.
AB  - INTRODUCTION: Food is a recognized trigger for most patients with irritable bowel
      syndrome (IBS). In recent years, an emerging evidence base has identified dietary
      manipulation as an important therapeutic approach in IBS. SOURCES OF DATA:
      Original and review articles were identified through selective searches performed
      on PubMed and Google Scholar. AREAS OF AGREEMENT: Randomized controlled trials
      have supported the use of a diet that restricts a group of short-chain
      carbohydrates known collectively as fermentable oligosaccharides, disaccharides,
      monosaccharides and polyols (FODMAPs). There is evidence that specific probiotics
      may improve symptoms in IBS. AREAS OF CONTROVERSY: The role of a high-fibre diet
      remains subject to ongoing debate with a lack of high-quality evidence. The long
      term durability and safety of a low FODMAP diet are unclear. GROWING POINTS: A
      paradigm shift has led to a focus on the relationship between diet and
      pathophysiological mechanisms in IBS such as effects on intestinal microbiota,
      inflammation, motility, permeability and visceral hypersensitivity. AREAS TIMELY
      FOR DEVELOPING RESEARCH: Future large, randomized controlled trials with rigorous
      end points are required. In addition, predictors of response need to be
      identified to offer personalized therapy.

PMID- 25601300
TI  - Sexually transmitted infections, benign prostatic hyperplasia and lower urinary
      tract symptom-related outcomes: results from the Prostate, Lung, Colorectal and
      Ovarian Cancer Screening Trial.
AB  - OBJECTIVE: To examine whether a history of sexually transmitted infections (STIs)
      or positive STI serology is associated with prevalent and incident benign
      prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS)-related outcomes
      in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. METHODS:
      Self-reported history of STIs (gonorrhoea, syphilis) was ascertained at baseline,
      and serological evidence of STIs (Chlamydia trachomatis, Trichomonas vaginalis,
      human papillomavirus (HPV)-16, HPV-18, herpes simplex virus type 2, human
      herpesvirus type 8 and cytomegalovirus) was detected in baseline serum specimens.
      We used data collected on the baseline questionnaire, as well as results from the
      baseline prostate-specific antigen (PSA) test and digital rectal examination
      (DRE), to define prevalent BPH/LUTS-related outcomes as evidence of LUTS (self
      reported diagnosis of an enlarged prostate/BPH, BPH surgery or nocturia [waking
      >=2 times/night to urinate]) and evidence of prostate enlargement (PSA > 1.4
      ng/mL or prostate volume >=30 mL) in men without prostate cancer. We created a
      similar definition of incident BPH using data from the follow-up questionnaire
      completed 5-13 years after enrolment (self-reported diagnosis of an enlarged
      prostate/BPH or nocturia), data on finasteride use during follow-up, and results
      from the follow-up PSA tests and DREs. We used Poisson regression with robust
      variance estimation to calculate prevalence ratios (PRs) in our cross-sectional
      analysis of self-reported (n = 32 900) and serologically detected STIs (n = 1
      143) with prevalent BPH/LUTS, and risk ratios in our prospective analysis of self
      reported STIs with incident BPH/LUTS (n = 5 226). RESULTS: Generally null results
      were observed for associations of a self-reported history of STIs and positive
      STI serologies with prevalent and incident BPH/LUTS-related outcomes, with the
      possible exception of T. vaginalis infection. This STI was positively associated
      with prevalent nocturia (PR 1.36, 95% confidence interval (CI) 1.18-1.65),
      prevalent large prostate volume (PR 1.21 95% CI 1.02-1.43), and any prevalent
      BPH/LUTS (PR 1.32 95% CI 1.09-1.61); too few men had information on both STI
      serologies and incident BPH/LUTS to investigate the associations between T.
      vaginalis infection and incident BPH/LUTS-related outcomes. CONCLUSIONS: Our
      findings do not support associations of several known STIs with BPH/LUTS-related
      outcomes, although T. vaginalis infection may warrant further study.

PMID- 25601301
TI  - Acute stroke imaging: feasibility and value of MR angiography with high spatial
      and temporal resolution for vessel assessment and perfusion analysis in patients
      with wake-up stroke.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging (MRI) provides
      information that can be used to estimate the symptom onset in patients with wake
      up stroke (WUS). Time-resolved MR angiography (MRA) is the fastest available MR
      sequence technique for vessel assessment, and the different phases acquired can
      provide information about cerebral perfusion. The aim of this study was to
      evaluate the diagnostic performance of time-resolved MRA both for the assessment
      of vessel morphology and for the feasibility of perfusion. MATERIALS AND METHODS:
      Nineteen patients with WUS were included. Image quality and vessel pathologies
      were evaluated and correlated to time-of-flight-MRA (n = 14), computed tomography
      angiography (n = 4), sonography (n = 12), and conventional angiography (n = 6).
      The temporal delay of signal enhancement in all pixels of the time-resolved MRA
      measurement after contrast injection was evaluated and compared to dynamic
      susceptibility contrast-enhanced (DSC) perfusion imaging (n = 13). RESULTS: Time
      resolved MRA resulted in the diagnosis of large vessel disease in 14 of 19
      patients, involving the internal carotids (n = 4), the vertebral arteries (n =
      3), and the circle of Willis (n = 10). All severe vascular pathologies which
      influence patients' acute stroke therapy were obtained by time-resolved MRA.
      Overestimation of stenoses in two of 14 patients resulted in sensitivity and
      specificity of 100% and 71%, respectively. Time-to-peak (TTP) estimations were
      hampered by movement artifacts in four patients (31%). Compared to DSC, the area
      of TTP delay was comparable in size and localization without relevant
      overestimation or underestimation. CONCLUSIONS: Time-resolved MRA is a valuable
      technique in patients with WUS with high sensitivity and high negative predictive
      value. Cerebral perfusion estimation can be performed in selected cases for
      therapy decision but can be hampered by patient movement.

PMID- 25601302
TI  - Imaging-histologic discordance at percutaneous biopsy of the lung.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to quantify the degree of
      imaging-histologic discordance in a cohort of patients undergoing computed
      tomography (CT)-guided lung biopsy for focal lung disease. MATERIALS AND METHODS:
      A retrospective review was performed of 186 patients who underwent percutaneous
      lung biopsy of a parenchymal lesion at our institution between January and
      December 2009. Diagnostic radiology reports of CT or positron emission tomography
      CTs performed before biopsy were used to classify the lesion as malignant or
      benign by five readers. Pathology reports of the biopsied lesions were classified
      by three readers. Inter-reader agreement and imaging-histologic concordance were
      quantified using kappa statistics. Discordant benign cases were then revisited to
      determine downstream effects. RESULTS: Inter-reader agreement on report content
      was substantial or almost perfect with kappas >0.783. Kappas for concordance were
      as follows: malignant (0.448), primary lung cancer (0.517), metastatic disease to
      lung (0.449), benign (0.510), and overall agreement (0.381). Of the twelve
      discordant benign cases that were revisited, four were found to be false
      negatives, resulting in a delay in diagnosis. CONCLUSIONS: Our study of imaging
      histologic discordance in percutaneous biopsy of lung lesions supports the need
      for imaging report standardization and improved integration and communication
      between the fields of radiology and pathology.

PMID- 25601304
TI  - Noncontrast MRA of pedal arteries in type II diabetes: effect of disease load on
      vessel visibility.
AB  - RATIONALE AND OBJECTIVES: Noncontrast magnetic resonance angiography (NC-MRA) of
      pedal artery remains challenging because of the global and regional disease load,
      tissue integrity, and altered microcirculation. This study aims to investigate
      the feasibility of the NC-MRA of pedal arteries with flow-sensitive dephasing
      prepared steady-state free precession (FSD-SSFP) and to explore the effect of
      disease load of type II diabetes on the vessel depiction. MATERIALS AND METHODS:
      FSD-SSFP was performed on a 1.5-T magnetic resonance system before the contrast
      enhanced MRA (CE-MRA) as a reference standard in 39 consecutive diabetic subjects
      (29 men and 16 women, aged 57.9 +/- 11.4 years). Two experienced radiologists
      evaluated the overall artery visibility (VA) and the contamination from soft
      tissue (SC) and veins (VC) with a four-point scale. Chronic complications and
      measures including random blood glucose (RBG), lipid panel, body mass index, risk
      of diabetic foot ulcers (RDF), and glycated hemoglobin (HbA1c) by the imaging
      were recorded as disease load indicators. Spearman rank correlation and ordinal
      regression were performed to investigate the effect of disease load on the
      depiction of pedal arteries. RESULTS: The measurement of RBG and RDF were
      significantly correlated with the VC in CE-MRA and with the overall visibility of
      pedal arteries in NC-MRA (P < .025 and P < .001, respectively). Blood pressure
      was the only parameter that was significantly associated with SC in NC-MRA with
      FSD-SSFP (P < .025). For CE-MRA the effect of RDF on the overall VA manifested a
      significant linear trend (P < .001), and the level of RBG was substantially
      associated with the VC (P < .025) without significantly impacting VA and SC.
      Hypertension only correlated with SC in NC-MRA. VA was found independent of the
      presence of diabetic nephropathy, coronary artery disease, abnormal lipid panel,
      HbA1c (75.0%), or optimized m1 value that ranged from 70 to 160 mT?ms(2)/m (mean,
      125 +/- 18 mT?ms(2)/m) in this study. CONCLUSIONS: FSD-SSFP proved to be a useful
      modality of NC-MRA for pedal artery imaging in diabetic patients. The vessel
      depiction is subject to the local and systemic disease load of type II diabetes.
      Technical optimization of the flow-sensitive dephasing gradient moment and
      properly choosing candidate would help augment the potential of this technique in
      patient care of peripheral artery disease.

PMID- 25601303
TI  - Evaluation of accuracy and precision of manual size measurements in chest
      tomosynthesis using simulated pulmonary nodules.
AB  - RATIONALE AND OBJECTIVES: To investigate the accuracy and precision of pulmonary
      nodule size measurements on chest tomosynthesis images. MATERIALS AND METHODS:
      Artificial ellipsoid-shaped nodules with known sizes were inserted in clinical
      chest tomosynthesis images. The volume of the nodules corresponded to that of a
      sphere with a diameter of 4.0, 8.0, or 12.0 mm. Four thoracic radiologists were
      given the task to determine the longest diameter of the nodules. All nodules were
      measured twice. Measurement accuracy in terms of the mean measurement error was
      determined. Intraobserver and interobserver variabilities, as well as variability
      because of differences between nodules and their locations, were used as measures
      of precision. RESULTS: The mean measurement error ranged from -0.3 to 0.1 mm for
      the nodule size groups and observers. Of the smallest nodules, the observers
      found 7-17 of total 50 nodules nonmeasurable. The intraobserver and interobserver
      variabilities were of similar magnitude, indicating relatively small differences
      between the observers. The internodule variability was in general larger,
      indicating that the different characteristics of the nodules and their location
      are sources of variability. CONCLUSIONS: The results suggest a high accuracy and
      precision for manual measurements of the nodules in chest tomosynthesis images.
      However, small nodules (<5.0 mm) may be difficult to measure at all because of
      poor visibility.

PMID- 25601305
TI  - Assessment of liver function and liver fibrosis with dynamic Gd-EOB-DTPA-enhanced
      MRI.
AB  - RATIONALE AND OBJECTIVES: To evaluate the ability of segmental linear fitting
      analysis of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid liver
      perfusion magnetic resonance imaging (MRI) to assess liver function and liver
      fibrosis. MATERIALS AND METHODS: Gadolinium ethoxybenzyl diethylenetriamine
      pentaacetic acid liver perfusion MRI was performed in 41 patients, and perfusion
      estimates were generated by segmental linear fitting analysis of the time
      intensity curves. The relationships of Tin, Tout, Kup, and the ratio between the
      signal intensities of the peak and the last phase with liver fibrosis stage and
      laboratory measurements of liver function were evaluated. RESULTS: Serum
      prealbumin concentration was significantly positively correlated with Kup and the
      signal intensity ratio and was significantly negatively correlated with Tin and
      Tout. Tin and Tout were significantly higher and Kup and the signal intensity
      ratio were significantly lower in patients with advanced fibrosis than those
      without. Tout was the best predictor of advanced fibrosis, with an area under the
      receiving operating characteristic curve of 0.843, a sensitivity of 100%, and a
      specificity of 80%. CONCLUSIONS: A new procedure of quantifying the hepatocyte
      specific uptake of a T1-enhancing contrast agent can be used to assess impaired
      hepatobiliary function. The parameters obtained from perfusion MRI have the
      potential to predict advanced fibrosis.

PMID- 25601306
TI  - Data analysis of the Lung Imaging Database Consortium and Image Database Resource
      Initiative.
AB  - RATIONALE AND OBJECTIVES: The Lung Image Database Consortium (LIDC) and Image
      Database Resource Initiative (IDRI) is the largest publicly available computed
      tomography (CT) image reference data set of lung nodules. In this article, a
      comprehensive data analysis of the data set and a uniform data model are
      presented with the purpose of facilitating potential researchers to have an in
      depth understanding to and efficient use of the data set in their lung cancer
      related investigations. MATERIALS AND METHODS: A uniform data model was designed
      for representation and organization of various types of information contained in
      different source data files. A software tool was developed for the processing and
      analysis of the database, which 1) automatically aligns and graphically displays
      the nodule outlines marked manually by radiologists onto the corresponding CT
      images; 2) extracts diagnostic nodule characteristics annotated by radiologists;
      3) calculates a variety of nodule image features based on the outlines of
      nodules, including diameter, volume, and degree of roundness, and so forth; 4)
      integrates all the extracted nodule information into the uniform data model and
      stores it in a common and easy-to-access data format; and 5) analyzes and
      summarizes various feature distributions of nodules in several different
      categories. Using this data processing and analysis tool, all 1018 CT scans from
      the data set were processed and analyzed for their statistical distribution.
      RESULTS: The information contained in different source data files with different
      formats was extracted and integrated into a new and uniform data model. Based on
      the new data model, the statistical distributions of nodules in terms of nodule
      geometric features and diagnostic characteristics were summarized. In the
      LIDC/IDRI data set, 2655 nodules >=3 mm, 5875 nodules <3 mm, and 7411 non-nodules
      are identified, respectively. Among the 2655 nodules, 1) 775, 488, 481, and 911
      were marked by one, two, three, or four radiologists, respectively; 2) most of
      nodules >=3 mm (85.7%) have a diameter <10.0 mm with the mean value of 6.72 mm;
      and 3) 10.87%, 31.4%, 38.8%, 16.4%, and 2.6% of nodules were assessed with a
      malignancy score of 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: This study
      demonstrates the usefulness of the proposed software tool to the potential users
      for an in-depth understanding of the LIDC/IDRI data set, therefore likely to be
      beneficial to their future investigations. The analysis results also demonstrate
      the distribution diversity of nodules characteristics, therefore being useful as
      a reference resource for assessing the performance of a new and existing nodule
      detection and/or segmentation schemes.

PMID- 25601307
TI  - Interpretive versus noninterpretive content in top-selling radiology textbooks:
      what are we teaching medical students?
AB  - RATIONALE AND OBJECTIVES: There are little data as to whether appropriate, cost
      effective, and safe ordering of imaging examinations are adequately taught in US
      medical school curricula. We sought to determine the proportion of
      noninterpretive content (such as appropriate ordering) versus interpretive
      content (such as reading a chest x-ray) in the top-selling medical student
      radiology textbooks. MATERIALS AND METHODS: We performed an online search to
      identify a ranked list of the six top-selling general radiology textbooks for
      medical students. Each textbook was reviewed including content in the text,
      tables, images, figures, appendices, practice questions, question explanations,
      and glossaries. Individual pages of text and individual images were
      semiquantitatively scored on a six-level scale as to the percentage of material
      that was interpretive versus noninterpretive. The predominant imaging modality
      addressed in each was also recorded. Descriptive statistical analysis was
      performed. RESULTS: All six books had more interpretive content. On average, 1.4
      pages of text focused on interpretation for every one page focused on
      noninterpretive content. Seventeen images/figures were dedicated to interpretive
      skills for every one focused on noninterpretive skills. In all books, the largest
      proportion of text and image content was dedicated to plain films (51.2%), with
      computed tomography (CT) a distant second (16%). The content on radiographs
      (3.1:1) and CT (1.6:1) was more interpretive than not. CONCLUSIONS: The current
      six top-selling medical student radiology textbooks contain a preponderance of
      material teaching image interpretation compared to material teaching
      noninterpretive skills, such as appropriate imaging examination selection,
      rational utilization, and patient safety.

PMID- 25601308
TI  - Multiple-division of self-propelled oil droplets through acetal formation.
AB  - We demonstrate a novel system that exhibits both self-propelled motion and
      division of micrometer-sized oil droplets induced by chemical conversion of the
      system components. Such unique dynamics were observed in an oil-in-water emulsion
      of a benzaldehyde derivative, an alkanol and a cationic surfactant at a low pH. 

PMID- 25601309
TI  - Bipolar disorder subtypes in children and adolescents: demographic and clinical
      characteristics from an Australian sample.
AB  - BACKGROUND: Bipolar disorder (BD) phenomenology in children and adolescents
      remains contentious. The study investigated Australian children and adolescents
      with bipolar I disorder (BD-I), bipolar II disorder (BD-II), or BD not otherwise
      specified (BD-NOS). METHODS: Index episode demographics, symptomatology,
      functioning and diagnostic data were compared for 88 participants (63 female)
      aged 8-18 years (M=14.8, SD=2.5) meeting DSM-IV-TR criteria for BD-I (n=24), BD
      II (n=13) or BD-NOS (n=51). RESULTS: BD-I had higher rates of previous episodes,
      psychotropic medication (compared to BD-II but not BD-NOS), rates of inpatient
      admissions (compared to BD-NOS), and number of inpatient admissions (compared to
      BD-II). BD-II had lower rates of lifetime depression and anxiety disorders,
      higher frequency of hypomania, shorter duration of illness, and fewer previous
      episodes. BD-NOS had younger age of onset, chronic course, irritability and mixed
      presentation. All BD subtypes had high rates of self-harm (69.3%), suicidal
      ideation (73.9%), suicide attempts (36.4%), psychiatric admission (55.7%), and
      psychosis (36.4%). LIMITATIONS: There were relatively small numbers of BD-I and
      BD-II. Diagnoses were based on retrospective recall. CONCLUSIONS: All BD subtypes
      had high levels of acuity and clinical risk. In accord with previous results, BD
      I and BD-II participants' phenomenology was consistent with classical
      descriptions of these subtypes. BD-NOS participants were younger, with less
      euphoric mania but otherwise phenomenologically on a continuum with BD-I,
      suggesting that child and adolescent BD-NOS may be an early and less
      differentiated phase of illness of BD-I or BD-II and hence a target for early
      intervention.

PMID- 25601310
TI  - Lamotrigine and GABAA receptor modulators interact with menstrual cycle phase and
      oral contraceptives to regulate mood in women with bipolar disorder.
AB  - OBJECTIVES: To examine the occurrence of menstrually-entrained mood cycling in
      women with treated bipolar disorder as compared to healthy controls, and to
      explore whether there is a specific effect of lamotrigine in dampening
      menstrually-entrained cyclicity of mood. METHODS: Observational comparison study
      of daily self-ratings of mood, sleep, and insomnia obtained over a mean of four
      menstrual cycles in 42 women with bipolar disorder taking lamotrigine as part of
      their treatment, 30 women with bipolar disorder receiving mood stabilizing
      regimens without lamotrigine, and 13 healthy controls, all with physiological
      menstrual cycles. Additional exploratory analysis of interactions between
      psychopharmacological regimen and hormonal contraceptive use in the group of
      women with bipolar disorder, with the addition of 19 women with bipolar disorder
      who were using hormonal contraceptives. RESULTS: Women treated for bipolar
      disorder manifested lower average mood, longer average nightly sleep duration,
      and greater fluctuations in mood and sleep across menstrual cycle phases than
      healthy controls. Women with bipolar disorder who were taking lamotrigine had
      less fluctuation in mood both within and across menstrual cycle phases, and were
      more similar to the control group than to women with bipolar disorder who were
      not taking lamotrigine in this respect. In addition, medications with GABA-A
      receptor modulating effects were found to result in improved mood ratings when
      combined with hormonal contraceptives. CONCLUSIONS: Menstrually-entrained mood
      fluctuation is present in women treated for bipolar disorder to a greater degree
      than in healthy controls. Lamotrigine may be of use in mitigating this
      fluctuation. GABA-A receptor modulators in general may act synergistically with
      hormonal contraceptives to enhance mood in women with bipolar disorder; this
      hypothesis merits further study.

PMID- 25601311
TI  - Public beliefs about and attitudes towards bipolar disorder: testing theory based
      models of stigma.
AB  - BACKGROUND: Given the vast literature into public beliefs and attitudes towards
      schizophrenia and depression, there is paucity of research on attitudes towards
      bipolar disorder despite its similar prevalence to schizophrenia. This study
      explored public beliefs and attitudes towards bipolar disorder and examined the
      relationship between these different components of stigma. METHOD: Using an
      online questionnaire distributed via email, social networking sites and public
      institutions, 753 members of the UK population were presented with a vignette
      depicting someone who met DSM-IV criteria for bipolar disorder. Causal beliefs,
      beliefs about prognosis, emotional reactions, stereotypes, and social distance
      were assessed in response to the vignette. Preacher and Hayes procedure for
      estimating direct and indirect effects of multiple mediators was used to examine
      the relationship between these components of stigma. RESULTS: Bipolar disorder
      was primarily associated with positive beliefs and attitudes and elicited a
      relatively low desire for social distance. Fear partially mediated the
      relationship between stereotypes and social distance. Biomedical causal beliefs
      reduced desire for social distance by increasing compassion, whereas fate causal
      beliefs increased it through eliciting fear. Psychosocial causal beliefs had
      mixed effects. LIMITATIONS: The measurement of stigma using vignettes and self
      report questionnaires has implications for ecological validity and participants
      may have been reluctant to reveal the true extent of their negative attitudes.
      CONCLUSIONS: Dissemination of these findings to people with bipolar disorder has
      implications for the reduction of internalised stigma in this population. Anti
      stigma campaigns should attend to causal beliefs, stereotypes and emotional
      reactions as these all play a vital role in discriminatory behaviour towards
      people with bipolar disorder.

PMID- 25601312
TI  - Group metacognitive therapy for repetitive negative thinking in primary and non
      primary generalized anxiety disorder: an effectiveness trial.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is a common and highly comorbid
      anxiety disorder characterized by repetitive negative thinking (RNT). Treatment
      trials tend to exclude individuals with non-primary GAD, despite this being a
      common presentation in real world clinics. RNT is also associated with multiple
      emotional disorders, suggesting that it should be targeted regardless of the
      primary disorder. This study evaluated the acceptability and effectiveness of
      brief group metacognitive therapy (MCT) for primary or non-primary GAD within a
      community clinic. METHODS: Patients referred to a specialist community clinic
      attended six, two-hour weekly sessions plus a one-month follow-up (N=52).
      Measures of metacognitive beliefs, RNT, symptoms, positive and negative affect,
      and quality of life were completed at the first, last, and follow-up sessions.
      RESULTS: Attrition was low and large intent-to-treat effects were observed on
      most outcomes, particularly for negative metacognitive beliefs and RNT. Treatment
      gains increased further to follow-up. Benchmarking comparisons demonstrated that
      outcomes compared favorably to longer disorder-specific protocols for primary
      GAD. LIMITATIONS: No control group or independent assessment of protocol
      adherence. CONCLUSIONS: Brief metacognitive therapy is an acceptable and powerful
      treatment for patients with primary or non-primary GAD.

PMID- 25601313
TI  - The isolation and antimicrobial activities of three monocylic sesquiterpenes from
      Syringa pinnatifolia.
AB  - We report the isolation of a new sesquiterpene, named as syripinol (1), and two
      known compounds from the volatile oil of the stems of Syringa pinnatifolia, for
      the first time. The structures of the isolated compounds were elucidated on the
      basis of spectroscopic methods including UV, IR, ESI-MS, 1D and 2D NMR
      techniques. The antibacterial activities of the compounds were also evaluated
      against various bacteria which showed good results. 

PMID- 25601314
TI  - Antimicrobial efficacy of granulysin-derived synthetic peptides in acne vulgaris.
AB  - BACKGROUND: Antimicrobial peptides are considered as a potential alternative to
      antibiotic treatment in acne vulgaris because the development of a resistant
      strain of Propionibacterium acnes is problematic. Granulysin can be regarded as
      an ideal substance with which to treat acne because it has antimicrobial and anti
      inflammatory effects. OBJECTIVES: This study was performed to explore the
      effectiveness of granulysin-derived peptides (GDPs) in killing P. acnes in vitro
      under a standard microbiologic assay and to evaluate their potential use in a
      topical agent for the treatment of acne vulgaris. METHODS: Twenty different
      peptides based on the known sequence of a GDP were synthesized and tested in
      vitro for antimicrobial activity. Thirty patients with facial acne vulgaris were
      instructed to apply a topical formulation containing synthetic GDP to acne
      lesions twice per day for 12 weeks. RESULTS: A newly synthesized peptide in which
      aspartic acid was substituted with arginine, and methionine was substituted with
      cysteine, showed the highest antimicrobial activity against P. acnes. Moreover,
      it was effective against both Gram-positive and Gram-negative bacteria in vitro.
      After treatment with the topical formulation containing 50 ppm of synthetic
      peptide for 12 weeks, a significant reduction in the number of pustules was
      observed, regardless of the increase in the number of comedones. In addition, a
      significant reduction in the clinical grade of acne based on the Korean Acne
      Grading System (KAGS) was evident. CONCLUSIONS: Synthesized GDP shows strong
      antimicrobial activity against P. acnes in vitro. The clinical improvement
      observed suggests a topical formulation containing the GDP has therapeutic
      potential for the improvement of inflammatory-type acne vulgaris by its
      antimicrobial activity.

PMID- 25601316
TI  - [25 years "Zeitschrift fur Medizinische Physik"].
AB  - The journal "Zeitschrift fur Medizinische Physik" was founded in 1990. The
      original idea of having a member journal for medical physicists in the German
      speaking region has been developed into an international notable journal over the
      last 25 years, being the official science journal of the German, Austrian, and
      Swiss societies of Medical Physics. In this article the evolution of our journal
      over the past 25 years is presented. 

PMID- 25601317
TI  - Determination of 2-, 3-, 4-methylpentanoic and cyclohexanecarboxylic acids in
      wine: development of a selective method based on solid phase extraction and gas
      chromatography-negative chemical ionization mass spectrometry and its application
      to different wines and alcoholic beverages.
AB  - A method to analyse 2-methylpentanoic, 3-methylpentanoic and 4-methylpentanoic
      acids as well as cyclohexanecarboxylic acid has been developed and applied to
      wine and other alcoholic beverages. Selective isolation with solid phase
      extraction, derivatization with 2,3,4,5,6-pentafluorobenzyl bromide at room
      temperature for 30 minutes, and further analysis by gas chromatography-mass
      spectrometry in negative chemical ionization mode provides detection limits
      between 0.4 and 2.4 ng/L. Good linearity up to 3.6 MUg/L, satisfactory
      reproducibility (RSD<10%) and signal recovery of around 100% represent a robust
      method of analysis. Concentration data of these analytes in wine and other
      alcoholic beverages are reported for the first time. The levels found ranged from
      the method detection limits to 2630 ng/L, 2040 ng/L and 3810 ng/L for 2-, 3- and
      4-methylpentanoic acids, respectively, and to 1780 ng/L for cyclohexanecarboxylic
      acid. There are significant differences depending on the type of wine or
      beverage. Distilled beverages, beer and aged wines have higher contents in
      methylpentanoic and cyclohexanecarboxylic acids.

PMID- 25601318
TI  - Possibilities of retention modeling and computer assisted method development in
      supercritical fluid chromatography.
AB  - The multi-modal retention mechanism in supercritical fluid chromatography (SFC)
      results in a non-linear dependency of log(k) on the fraction of organic solvent
      phi and log(phi). In the present study, the possibility of retention modeling for
      method development purposes in SFC was investigated, considering several non
      linear isocratic relationships. Therefore, both isocratic and gradient runs were
      performed, involving different column chemistries and analytes possessing diverse
      physico-chemical properties. The isocratic retention data of these compounds
      could be described accurately using the non-linear retention models typically
      used in HILIC and reversed-phase LC. The interconversion between isocratic and
      gradient retention data was found to be less straightforward than in RPLC and
      HILIC because of pressure effects. The possibility of gradient predictions using
      gradient scouting runs to estimate the retention parameters was investigated as
      well, showing that predictions for other gradients with the same starting
      conditions were acceptable (always below 5%), whereas prediction errors for
      gradients with a different starting condition were found to be highly dependent
      on the compound. The second part of the study consisted of the gradient
      optimization of two pharmaceutical mixtures (one involving atorvastatin and four
      related impurities, and one involving a 16 components mixture including eight
      drugs and their main phase I metabolites). This could be done via individual
      retention modeling based on gradient scouting runs. The best linear gradient was
      found via a grid search and the best multi-segment gradient via the previously
      published one-segment-per-component search. The latter improved the resolution
      between the critical pairs for both mixtures, while still giving accurate
      prediction errors (using the same starting concentrations as the gradient
      scouting runs used to build the model). The optimized separations were found in
      less than 3 h and 8 h of analysis time (including equilibration times),
      respectively.

PMID- 25601315
TI  - Structure and function of serotonin G protein-coupled receptors.
AB  - Serotonin receptors are prevalent throughout the nervous system and the
      periphery, and remain one of the most lucrative and promising drug discovery
      targets for disorders ranging from migraine headaches to neuropsychiatric
      disorders such as schizophrenia and depression. There are 14 distinct serotonin
      receptors, of which 13 are G protein-coupled receptors (GPCRs), which are targets
      for approximately 40% of the approved medicines. Recent crystallographic and
      biochemical evidence has provided a converging understanding of the basic
      structure and functional mechanics of GPCR activation. Currently, two GPCR
      crystal structures exist for the serotonin family, the 5-HT1B and 5-HT2B
      receptor, with the antimigraine and valvulopathic drug ergotamine bound. The
      first serotonin crystal structures not only provide the first evidence of
      serotonin receptor topography but also provide mechanistic explanations into
      functional selectivity or biased agonism. This review will detail the findings of
      these crystal structures from a molecular and mutagenesis perspective for driving
      rational drug design for novel therapeutics incorporating biased signaling.

PMID- 25601319
TI  - Protein behavior at surfaces: orientation, conformational transitions and
      transport.
AB  - Chromatography is the key technology in protein purification as well as in
      protein refolding. Taking the scientific development and technological innovation
      of protein chromatography as the objective, this article is devoted to an
      overview of protein behavior at chromatographic surfaces, including protein
      orientation, conformational transitions (unfolding and refolding), and protein
      transport. Recent advances achieved by using molecular simulations as well as
      theoretical and experimental investigations are elaborated and discussed with
      emphasis on their implications to the rational design of novel chromatographic
      surfaces or materials and mobile phase conditions for the development of high
      performance protein chromatography. 

PMID- 25601321
TI  - Palliative Care Caregivers' Grief Mediators: A Prospective Study.
AB  - The aim of the study is to identify the mediators of complicated grief in a
      Portuguese sample of caregivers. Grief mediators were prospectively evaluated
      using a list of risk factors completed by the palliative care team members,
      during the predeath and bereavement period. More than 6 months after the death,
      we applied PG-13 to diagnose prolonged grief disorder (PGD). The sample was
      composed of 64 family caregivers. Factors associated with PGD were insecure and
      dependent relationship, unresolved family crisis, and the perceived deterioration
      and disfigurement of the patient. The results show relational factors are
      relevant, but we must consider the reciprocal influence among factors, as well as
      their impact on specific symptoms. 

PMID- 25601320
TI  - Latent autoimmune diabetes of the adult: current knowledge and uncertainty.
AB  - Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen
      (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies
      compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at
      diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis
      to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes
      of the adult (LADA). This latter phenotype is the most prevalent form of adult
      onset autoimmune diabetes and probably the most prevalent form of autoimmune
      diabetes in general. Although LADA is associated with the same genetic and
      immunological features as childhood-onset Type 1 diabetes, it also shares some
      genetic features with Type 2 diabetes, which raises the question of genetic
      heterogeneity predisposing to this form of the disease. The potential value of
      screening patients with adult-onset diabetes for diabetes-associated
      autoantibodies to identify those with LADA is emphasized by their lack of
      clinically distinct features, their different natural history compared with Type
      2 diabetes and their potential need for a dedicated management strategy. The fact
      that, in some studies, patients with LADA show worse glucose control than
      patients with Type 2 diabetes, highlights the need for further therapeutic
      studies. Challenges regarding classification, epidemiology, genetics, metabolism,
      immunology, clinical presentation and treatment of LADA were discussed at a 2014
      workshop arranged by the Danish Diabetes Academy. The presentations and
      discussions are summarized in this review, which sets out the current ideas and
      controversies surrounding this form of diabetes. 

PMID- 25601322
TI  - Improving fertilization rate in ICSI cycles by adding myoinositol to the semen
      preparation procedures: a prospective, bicentric, randomized trial on sibling
      oocytes.
AB  - PURPOSE: To evaluate whether the in vitro incubation of spermatozoa with
      myoinositol may improve the fertilization rate in ICSI cycles. METHODS: This is a
      prospective, bicentric, randomized study on 500 MII sibling oocytes injected in
      78 ICSI cycles performed between March and October 2013. Randomization of the
      oocytes into two groups was performed at the time of the denudation.
      Fertilization rates (per oocyte injected with spermatozoa treated with
      myoinositol versus per oocyte injected with spermatozoa treated with placebo)
      were measured as primary outcome and embryo morphology as secondary outcome.
      Clinical outcomes were also documented. RESULT (S): Fertilization rate (78.9 +/-
      28.6% vs 63.2 +/- 36.7, P = 0.002) and percentage of grade A embryos on day 3
      (59.8 +/- 35.6% vs 43.5 +/- 41.5, P = 0.019) were significantly higher when
      spermatozoa were treated in vitro with myoinositol versus placebo. No differences
      were found for the expanded blastocyst formation rate. CONCLUSION (S): In vitro
      treatment of spermatozoa with myoinositol may optimize ICSI outcomes by improving
      the fertilization rate and embryo quality on day 3. The improvement of the number
      and the quality of embryos available in an ICSI cycle may have clinical utility
      if these findings can be confirmed.

PMID- 25601323
TI  - How are we using systemic drugs to treat psoriasis in children? An insight into
      current clinical U.K. practice.

PMID- 25601324
TI  - Physical education or playtime: which is more effective at promoting physical
      activity in primary school children?
AB  - BACKGROUND: School physical education (PE) and playtime provide important
      opportunities for physical activity (PA). However, little research has assessed
      PA during primary school PE using accelerometry or compared PA during different
      lesson types. There is also a lack of research comparing PA during PE and
      playtime, despite suggestions that playtime promotes more PA. The primary aim of
      this study was to determine which types of PE lesson are most facilitative of PA.
      The secondary aim was to determine whether children are more active during PE or
      playtime. METHODS: Descriptive and fitness data were assessed in 20 children aged
      8-9years from a single school. Over eight consecutive weeks PA was assessed
      during PE lessons, which were classified as either team games or movement
      activities. At the mid-week of data collection playtime PA was also assessed. PA
      was assessed using accelerometry and the percentage of time spent in moderate to
      vigorous PA (MVPA) calculated. Paired t-tests were used to compare MVPA during
      movement lessons and team games lessons and during PE and playtime. RESULTS:
      Children spent 9.5% of PE lessons in MVPA and engaged in significantly more MVPA
      during team games (P < 0.001). MVPA was also significantly higher during PE than
      playtime (P < 0.01). CONCLUSIONS: Children do not engage in sufficient PA during
      PE, but are most active during team games lessons; whilst PA during playtime is
      lower than PE. Interventions to increase PA during both PE and playtime are
      therefore required. PE interventions should target games lessons as they dominate
      the curriculum, encourage most PA and present the greatest potential for change.
      Playtime interventions should encourage participation in active games through the
      provision of playground equipment and markings.

PMID- 25601325
TI  - A molecular view of cisplatin's mode of action: interplay with DNA bases and
      acquired resistance.
AB  - The interaction of the widely used anticancer drug cisplatin with DNA bases was
      studied by EXAFS and vibrational spectroscopy (FTIR, Raman and INS), coupled with
      DFT/plane-wave calculations. Detailed information was obtained on the local
      atomic structure around the Pt(ii) centre, both in the cisplatin-purine (adenine
      and guanine) and cisplatin-glutathione adducts. Simultaneous neutron and Raman
      scattering experiments allowed us to obtain a reliable and definite picture of
      this cisplatin interplay with its main pharmacological target (DNA), at the
      molecular level. The vibrational experimental spectra were fully assigned in the
      light of the calculated pattern for the most favoured geometry of each drug
      purine adduct, and cisplatin's preference for guanine (G) relative to adenine (A)
      within the DNA double helix was experimentally verified: a complete N by S
      substitution in the metal coordination sphere was only observed for [cDDP-A2],
      reflecting a somewhat weaker Pt-A binding relative to Pt-G. The role of
      glutathione on the drug's pharmacokinetics, as well as on the stability of
      platinated DNA adducts, was evaluated as this is the basis for glutathione
      mediated intracellular drug scavenging and in vivo resistance to Pt-based
      anticancer drugs. Spectroscopic evidence of the metal's preference for
      glutathione's sulfur over purine's nitrogen binding sites was gathered, at least
      two sulfur atoms being detected in platinum's first coordination sphere. 

PMID- 25601326
TI  - (1->3)-alpha-D-Glucans from Aspergillus spp.: Structural Characterization and
      Biological Study on their Carboxymethylated Derivatives.
AB  - Alkali-soluble polysaccharides (ASPs) were isolated from the cell wall of four
      Aspergillus species (A. fumigatus, A. nidulans, A. niger, and A. wentii). The
      chemical and spectroscopic investigations (immunofluorescent labelling,
      composition analysis, methylation analysis, FTIR, and 1H NMR) indicated that the
      ASPs were polymers composed almost exclusively of (1->3)-linked alpha-D-glucose.
      After carboxymethylation (CM), the activity of (1->3)-alpha-D-glucans on three
      human cell lines (HSF, HeLa, and Jurkat) was assessed. Anti-proliferative,
      cytotoxic, and free radical scavenging action of CM-alpha-D-glucans was analysed.
      All the tested CM-alpha-D-glucans decreased cellular metabolism. However,
      incubation with CM-alpha-D-glucan from A. wentii and A. niger increased (by ca.
      50%) the viability of HSF cells. Moreover, an over 5-fold increase in the
      viability was found for Jurkat cells incubated with CM-alpha-D-glucans from A.
      fumigatus and A. nidulans. The CM-(1->3)-alpha-D-glucans from the tested
      Aspergillus species expressed no free radical scavenging action. Fluorescent
      staining revealed that CM-alpha-D-glucans exerted slight toxic effects on cell
      viability and no action on F-actin filaments of cellular cytoskeleton
      organization. 

PMID- 25601327
TI  - Targets Involved in Cardioprotection by the Non-Anesthetic Noble Gas Helium.
AB  - Research data from the past decade indicate that noble gases like xenon and
      helium exert profound cardioprotection when applied before, during or after organ
      ischemia. Of all noble gases, especially helium, has gained interest in the past
      years because it does not have an anesthetic "side effect" like xenon, allowing
      application of this specific gas in numerous clinical ischemia/reperfusion
      situations. Because helium has several unique characteristics and no hemodynamic
      side effects, helium could be administered in severely ill patients.
      Investigations in animals as well as in humans have proven that this noble gas is
      not completely inert and can induce several biological effects. Though the
      underlying molecular mechanisms of helium-induced cardiac protection are still
      not yet fully understood, recently different signaling pathways have been
      elucidated.

PMID- 25601328
TI  - Intestinal microbiota: a regulator of intestinal inflammation and cardiac
      ischemia?
AB  - Inflammatory bowel diseases (IBD) are chronic, relapsing and remitting
      gastrointestinal (GI) disorders of unknown etiology. IBD patients commonly
      exhibit extra-intestinal manifestations and complications of an inflammatory
      nature, presenting with disorders such as ankylosing spondylitis, uveitis and
      vasculitis. Although the metabolic syndrome is less prevalent in patients with
      IBD, they are at an increased risk for atherosclerosis and cardiovascular events.
      Considerable evidence supports the role of GI microbiota in the development of
      IBD. Recent studies have also shown a significant interaction between the
      metabolites of gut microbiota and the development of cardiovascular disease. Here
      we hypothesize that dysbiosis and/or abnormalities in the function of the
      intestinal microbiota promote cardiovascular disease in IBD patients, explaining
      the increased risk of cardiovascular events in these patients. 

PMID- 25601329
TI  - The Impact of the Emerging Genomics Data on the Management of Agerelated
      Phenotypes in the Context of Cellular Senescence.
AB  - Before the last decade, attempts to identify the genetic factors involved in the
      susceptibility to age-related complex diseases such as cardiovascular disease,
      diabetes and cancer had very limited success. Recently, two important
      advancements have provided new opportunities to improve our knowledge in this
      field. Firstly, it has emerged the concept of studying the molecular mechanisms
      underlying the age related decline of the organism (such as cellular senescence),
      rather than the genetics of single disorders. In addition, advances in DNA
      technology have uncovered an incredible number of common susceptibility variants
      for several complex traits. Despite these progresses, the translation of these
      discoveries into clinical practice has been very difficult. To date, several
      attempts in translating genomics to medicine are being carried out to look for
      the best way by which genomic discoveries may improve our understanding of
      fundamental issues in the prediction and prevention of some complex diseases. The
      successful strategy seems to be testing simultaneously multiple susceptibility
      variants in combination with traditional risk factors. In fact, such approach
      showed that genetic factors substantially improve the prediction of complex
      diseases especially for coronary heart disease and prostate cancer, making
      possible appropriate behavioural and medical interventions. In the future, the
      identification of new genetic variants and their inclusion into current risk
      profile models will probably improve the discrimination power of these models for
      other complex diseases such as type 2 diabetes mellitus and breast cancer. On the
      other hand, for traits with low heritability, this improvement will probably be
      negligible, and this will urge further researches on the role played by
      traditional and newly discovered non-genetic risk factors.

PMID- 25601330
TI  - BNP in children with congenital cardiac disease: is there now sufficient evidence
      for its routine use?
AB  - Interest in brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic
      peptide (NT-proBNP) in the management of children with CHD has increased. There
      are, however, no current guidelines for their routine use. The aim of this review
      article is to provide an update on the data regarding the use of BNP/NT-proBNP in
      the evaluation and surgical treatment of children with CHD. BNP/NT-proBNP levels
      in children with CHD vary substantially according to age, laboratory assay
      methods, and the specific haemodynamics associated with the individual congenital
      heart lesion. The accuracy of BNP/NT-proBNP as supplemental markers in the
      integrated screening, diagnosis, management, and follow-up of CHD has been
      established. In particular, the use of BNP/NT-proBNP as a prognostic indicator in
      paediatric cardiac surgery has been widely demonstrated, as well as its role in
      the subsequent follow-up of surgical patients. Most of the data, however, are
      derived from single-centre retrospective studies using multivariable analysis;
      prospective, randomised clinical trials designed to evaluate the clinical utility
      and cost-effectiveness of routine BNP/NT-proBNP use in CHD are lacking. The
      results of well-designed, prospective clinical trials should assist in
      formulating guidelines and expert consensus recommendations for its use in
      patients with CHD. Finally, the use of new point-of-care testing methods that use
      less invasive sampling techniques - capillary blood specimens - may contribute to
      a more widespread use of the BNP assay, especially in neonates and infants, as
      well as contribute to the development of screening programmes for CHD using this
      biomarker. 

PMID- 25601331
TI  - The impact of digital media on health: children's perspectives.
AB  - OBJECTIVES: Previous research has mainly focused on the effects of excessive
      digital media use or overuse on the health of children, primarily utilizing
      quantitative designs. More research should be conducted on general populations of
      children, rather than focusing exclusively on excessive technology users. This
      qualitative study describes technology's impact on physical and mental health
      from children's perspectives. METHODS: Focus groups and interviews were conducted
      with children between the ages of 9 and 16 in 9 European countries (N = 368).
      During focus groups and interviews, researchers asked what children perceive as
      being potentially negative or problematic while using the internet and
      technology. RESULTS: In this study, children reported several physical and mental
      health problems without indicating internet addiction or overuse. Physical health
      symptoms included eye problems, headaches, not eating, and tiredness. For mental
      health symptoms, children reported cognitive salience of online events,
      aggression, and sleeping problems. Sometimes they reported these problems within
      30 min of technology usage. This suggests that even shorter time usage can cause
      self-reported health problems for some children. CONCLUSIONS: Qualitative
      methodology helps to understand what children's perspectives are concerning the
      impact of digital media on health. We recommend future studies focused on average
      technology users and low technology users to determine whether average levels of
      technology usage relate to health problems of children. Parents and teachers
      should also be informed about the possible physical and mental health issues
      associated with children's average usage of technology.

PMID- 25601332
TI  - The organizational and clinical impact of integrating bedside equipment to an
      information system: a systematic literature review of patient data management
      systems (PDMS).
AB  - OBJECTIVE: The introduction of an information system integrated to bedside
      equipment requires significant financial and resource investment; therefore
      understanding the potential impact is beneficial for decision-makers. However, no
      systematic literature reviews (SLRs) focus on this topic. This SLR aims to gather
      evidence on the impact of the aforementioned system, also known as a patient data
      management system (PDMS) on both organizational and clinical outcomes. MATERIALS
      AND METHODS: A literature search was performed using the databases Medline/PubMed
      and CINHAL for English articles published between January 2000 and December 2012.
      A quality assessment was performed on articles deemed relevant for the SLR.
      RESULTS: Eighteen articles were included in the SLR. Sixteen articles
      investigated the impact of a PDMS on the organizational outcomes, comprising
      descriptive, quantitative and qualitative studies. A PDMS was found to reduce the
      charting time, increase the time spent on direct patient care and reduce the
      occurrence of errors. Only two articles investigated the clinical impact of a
      PDMS. Both reported an improvement in clinical outcomes when a PDMS was
      integrated with a clinical decision support system (CDSS). CONCLUSIONS: A PDMS
      has shown to offer many advantages in both the efficiency and the quality of care
      delivered to the patient. In addition, a PDMS integrated to a CDSS may improve
      clinical outcomes, although further studies are required for validation.

PMID- 25601333
TI  - Cataract surgery and age-related macular degeneration. An evidence-based update.
AB  - PURPOSE: Age-related macular degeneration (AMD) and cataract often coexist in
      patients and concerns that cataract surgery is associated with an increased risk
      of incidence or progression of existing AMD has been raised. This systematic
      review and meta-analysis is focused on presenting the evidence concerning
      progression of AMD in patients undergoing cataract surgery. METHODS: We performed
      a systematic literature search in the PubMed, Medline, Cochrane Library and
      CINAHL databases. Two randomized trials and two case-control trials were
      identified. Quality of the studies was assessed using the Cochrane risk of bias
      tool, data were extracted, and meta-analyses were performed. Quality of the
      available evidence was evaluated using the GRADE system. RESULTS: We found that
      visual acuity at 6-12 months follow-up was significantly better (6.5-7.5 letters)
      in eyes that had undergone cataract surgery than in unoperated eyes, but the
      included number of subjects was small, and hence, the quality of evidence was
      downgraded to moderate. We did not find an increased risk of progression to
      exudative AMD 6-12 months after cataract surgery [RR 3.21 (0.14-75.68)], but the
      included number of subjects was small, and thus, the quality of the evidence was
      moderate. CONCLUSION: Cataract surgery increases visual acuity without an
      increased risk of progression to exudative AMD, but further research with longer
      follow-up is encouraged.

PMID- 25601334
TI  - Induction of gynogenetic and androgenetic haploid and doubled haploid development
      in the brown trout (Salmo trutta Linnaeus 1758).
AB  - Gynogenetic and androgenetic brown trout (Salmo trutta Linnaeus 1758) haploids
      (Hs) and doubled haploids (DHs) were produced in the present research. Haploid
      development was induced by radiation-induced genetic inactivation of spermatozoa
      (gynogenesis) or eggs (androgenesis) before insemination. To provide DHs,
      gynogenetic and androgenetic haploid zygotes were subjected to the high pressure
      shock to suppress the first mitotic cleavage. Among haploids, gynogenetic embryos
      were showing lower mortality when compared to the androgenetic embryos; however,
      most of them die before the first feeding stage. Gynogenetic doubled haploids
      provided in the course of the brown trout eggs activation performed by homologous
      and heterologous sperm (rainbow trout) were developing equally showing hatching
      rates of 14.76 +/- 2.4% and 16.14 +/- 2.90% and the survival rates at the first
      feeding stage of 10.48 +/- 3.48% and 12.78 +/- 2.18%, respectively.
      Significantly, lower survival rate was observed among androgenetic progenies from
      the diploid groups with only few specimens that survived to the first feeding
      stage. Cytogenetic survey showed that among embryos from the diploid variants of
      the research, only gynogenetic individuals possessed doubled sets of chromosomes.
      Thus, it is reasonable to assume that radiation employed for the genetic
      inactivation of the brown trout eggs misaligned mechanism responsible for the
      cell divisions and might have delayed or even arrested the first mitotic cleavage
      in the androgenetic brown trout zygotes. Moreover, protocol for the radiation
      induced inactivation of the paternal and maternal genome should be adjusted as
      some of the cytogenetically surveyed gynogenetic and androgenetic embryos
      exhibited fragments of the irradiated chromosomes.

PMID- 25601335
TI  - Randomized multicenter follow-up trial on the effect of radiotherapy for plantar
      fasciitis (painful heels spur) depending on dose and fractionation - a study
      protocol.
AB  - BACKGROUND: An actual clinical trial showed the effect of low dose radiotherapy
      in painful heel spur (plantar fasciitis) with single doses of 1.0 Gy and total
      doses of 6.0 Gy applied twice weekly. Furthermore, a lot of animal experimental
      and in vitro data reveals the effect of lower single doses of 0.5 Gy which may be
      superior in order to ease pain and reduce inflammation in patients with painful
      heel spur. Our goal is therefore to transfer this experimentally found effect
      into a randomized multicenter trial. STUDY DESIGN/METHODS: This was a controlled,
      prospective, two-arm phase III-multicenter trial. The standard arm consisted of
      single fractions of 1.0 Gy applied two times a week, for a total dose of 6.0 Gy
      (total therapy time: 3 weeks). The experimental arm consisted of single fractions
      of 0.5 Gy applied 3 times a week, for a total dose of 6.0 Gy (total therapy time:
      4 weeks). Following a statistical power calculation, there were 120 patients for
      each investigation arm. The main inclusion criteria were: age > = 40 years,
      clinical and radiologically diagnosed painful heel spur (plantar fasciitis), and
      current symptoms for at least 6 months. The main exclusion criteria were: former
      local trauma, surgery or radiotherapy of the heel; pregnant or breastfeeding
      women; and a pre-existing severe psychiatric or psychosomatic disorder. METHODS:
      After approving a written informed consent the patients are randomized by a
      statistician into one of the trial arms. After radiotherapy, the patients are
      seen after six weeks, after twelve weeks and then every twelve weeks up to 48
      weeks. Additionally, they receive a questionnaire every six weeks after the
      follow-up examinations up to 48 weeks. The effect is measured using the visual
      analogue scale of pain (VAS), the calcaneodynia score according to Rowe and the
      SF-12 score. The primary endpoint is the pain relief three months after therapy.
      Patients of both therapy arms with an insufficient result are offered a second
      radiotherapy series applying the standard dose (equally in both arms). This trial
      protocol has been approved by the expert panel of the DEGRO as well as by the
      Ethics committee of the Saarland Physicians' chamber. TRIAL REGISTRATION: Current
      trial registration at German Clinical Trials Register with the number
      DRKS00004458.

PMID- 25601336
TI  - [18F]FE@SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo
      study in rodents.
AB  - PURPOSE: The adenosine A3 receptor (A3R) is involved in cardiovascular,
      neurological and tumour-related pathologies and serves as an exceptional
      pharmaceutical target in the clinical setting. A3R antagonists are considered
      antiinflammatory, antiallergic and anticancer agents, and to have potential for
      the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET
      tracer would be highly beneficial for the diagnosis and therapy monitoring of
      these diseases. Therefore, in this preclinical in vivo study we evaluated the
      potential as a PET tracer of the A3R antagonist [(18)F]FE@SUPPY. METHODS: Rats
      were injected with [(18)F]FE@SUPPY for baseline scans and blocking scans (A3R
      with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each).
      Additionally, metabolism was studied in plasma and brain. In a preliminary
      experiment in a mouse xenograft model (mice injected with cells expressing the
      human A3R; three animals), the animals received [(18)F]FE@SUPPY and [(18)F]FDG.
      Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice).
      In vitro stability of [(18)F]FE@SUPPY in human and rat plasma was also evaluated.
      RESULTS: [(18)F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in
      the brain. Pretreatment with MRS1523 led to a decrease in [(18)F]FE@SUPPY uptake
      (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24
      fold increase in [(18)F]FE@SUPPY uptake (p = 0.09) in rat brain. There was no
      significant difference in metabolites in plasma and brain in the treatment
      groups. However, plasma concentrations of [(18)F]FE@SUPPY were reduced to levels
      similar to those in rat brain after blocking. In contrast to [(18)F]FDG uptake (p
      = 0.12), the xenograft model showed significantly increased uptake of
      [(18)F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p =
      0.03). [(18)F]FE@SUPPY was stable in human plasma. CONCLUSION: Selective and
      significant tracer uptake of [(18)F]FE@SUPPY was found in xenografted mice
      injected with cells expressing human A3R. This finding supports the strategy of
      evaluating [(18)F]FE@SUPPY in "humanized animal models". In conclusion,
      preclinical evaluation points to the suitability of [(18)F]FE@SUPPY as an A3R PET
      tracer in humans.

PMID- 25601337
TI  - Assessment of bone marrow inflammation in patients with myelofibrosis: an 18F
      fluorodeoxyglucose PET/CT study.
AB  - PURPOSE: Myelofibrosis is a haematopoietic stem cell neoplasm characterized by
      bone marrow inflammation, reactive marrow fibrosis and extramedullary
      haematopoiesis. The aim of this study was to determine if (18)F-FDG PET/CT can be
      used to noninvasively visualize and quantify the extent and activity of bone
      marrow involvement. METHODS: In 30 patients, the biodistribution of (18)F-FDG was
      analysed by measuring the standardized uptake value in the bone marrow
      compartment and spleen. Imaging findings were compared with laboratory,
      cytogenetic and histopathological data. RESULTS: Retention of (18)F-FDG was
      observed in bone marrow and spleen. Bone marrow involvement varied, ranging from
      mildly increased uptake in the central skeleton to extensive uptake in most parts
      of the skeleton. The extent of bone marrow involvement decreased over time from
      initial diagnosis (r s  = -0.43, p = 0.019). Metabolic activity of the bone
      marrow decreased as the histopathological grade of fibrosis increased (r s  = 
      0.37, p = 0.04). There was a significant positive correlation between the
      metabolic activity of the bone marrow and that of the spleen (p = 0.04).
      CONCLUSION: (18)F-FDG PET/CT is as a promising technique for the quantitation of
      bone marrow inflammation in myelofibrosis. Our data indicate that the intensity
      of bone marrow (18)F-FDG uptake decreases as bone marrow fibrosis increases.
      Further evaluation in prospective studies is required to determine the potential
      clinical impact and prognostic significance of PET.

PMID- 25601338
TI  - Abiraterone's efficacy confirmed; time to aim higher.

PMID- 25601339
TI  - Immunotherapy improves overall survival in pancreatic cancer.

PMID- 25601340
TI  - Dose escalation in lung cancer: have we gone full circle?

PMID- 25601343
TI  - Adjuvant treatment for HER2-positive breast cancer.

PMID- 25601344
TI  - Combined treatment for only half of Hodgkin's patients.

PMID- 25601342
TI  - Standard-dose versus high-dose conformal radiotherapy with concurrent and
      consolidation carboplatin plus paclitaxel with or without cetuximab for patients
      with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two
      by-two factorial phase 3 study.
AB  - BACKGROUND: We aimed to compare overall survival after standard-dose versus high
      dose conformal radiotherapy with concurrent chemotherapy and the addition of
      cetuximab to concurrent chemoradiation for patients with inoperable stage III non
      small-cell lung cancer. METHODS: In this open-label randomised, two-by-two
      factorial phase 3 study in 185 institutions in the USA and Canada, we enrolled
      patients (aged >= 18 years) with unresectable stage III non-small-cell lung
      cancer, a Zubrod performance status of 0-1, adequate pulmonary function, and no
      evidence of supraclavicular or contralateral hilar adenopathy. We randomly
      assigned (1:1:1:1) patients to receive either 60 Gy (standard dose), 74 Gy (high
      dose), 60 Gy plus cetuximab, or 74 Gy plus cetuximab. All patients also received
      concurrent chemotherapy with 45 mg/m(2) paclitaxel and carboplatin once a week
      (AUC 2); 2 weeks after chemoradiation, two cycles of consolidation chemotherapy
      separated by 3 weeks were given consisting of paclitaxel (200 mg/m(2)) and
      carboplatin (AUC 6). Randomisation was done with permuted block randomisation
      methods, stratified by radiotherapy technique, Zubrod performance status, use of
      PET during staging, and histology; treatment group assignments were not masked.
      Radiation dose was prescribed to the planning target volume and was given in 2 Gy
      daily fractions with either intensity-modulated radiation therapy or three
      dimensional conformal radiation therapy. The use of four-dimensional CT and image
      guided radiation therapy were encouraged but not necessary. For patients assigned
      to receive cetuximab, 400 mg/m(2) cetuximab was given on day 1 followed by weekly
      doses of 250 mg/m(2), and was continued through consolidation therapy. The
      primary endpoint was overall survival. All analyses were done by modified
      intention-to-treat. The study is registered with ClinicalTrials.gov, number
      NCT00533949. FINDINGS: Between Nov 27, 2007, and Nov 22, 2011, 166 patients were
      randomly assigned to receive standard-dose chemoradiotherapy, 121 to high-dose
      chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab, and 110
      to high-dose chemoradiotherapy and cetuximab. Median follow-up for the
      radiotherapy comparison was 22.9 months (IQR 27.5-33.3). Median overall survival
      was 28.7 months (95% CI 24.1-36.9) for patients who received standard-dose
      radiotherapy and 20.3 months (17.7-25.0) for those who received high-dose
      radiotherapy (hazard ratio [HR] 1.38, 95% CI 1.09-1.76; p=0.004). Median follow
      up for the cetuximab comparison was 21.3 months (IQR 23.5-29.8). Median overall
      survival in patients who received cetuximab was 25.0 months (95% CI 20.2-30.5)
      compared with 24.0 months (19.8-28.6) in those who did not (HR 1.07, 95% CI 0.84
      1.35; p=0.29). Both the radiation-dose and cetuximab results crossed protocol
      specified futility boundaries. We recorded no statistical differences in grade 3
      or worse toxic effects between radiotherapy groups. By contrast, the use of
      cetuximab was associated with a higher rate of grade 3 or worse toxic effects
      (205 [86%] of 237 vs 160 [70%] of 228 patients; p<0.0001). There were more
      treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups
      (radiotherapy comparison: eight vs three patients; cetuximab comparison: ten vs
      five patients). There were no differences in severe pulmonary events between
      treatment groups. Severe oesophagitis was more common in patients who received
      high-dose chemoradiotherapy than in those who received standard-dose treatment
      (43 [21%] of 207 patients vs 16 [7%] of 217 patients; p<0.0001). INTERPRETATION:
      74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not
      better than 60 Gy plus concurrent chemotherapy for patients with stage III non
      small-cell lung cancer, and might be potentially harmful. Addition of cetuximab
      to concurrent chemoradiation and consolidation treatment provided no benefit in
      overall survival for these patients. FUNDING: National Cancer Institute and
      Bristol-Myers Squibb.

PMID- 25601345
TI  - Commercial solariums banned in Australia.

PMID- 25601341
TI  - Abiraterone acetate plus prednisone versus placebo plus prednisone in
      chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU
      AA-302): final overall survival analysis of a randomised, double-blind, placebo
      controlled phase 3 study.
AB  - BACKGROUND: Abiraterone acetate plus prednisone significantly improved
      radiographic progression-free survival compared with placebo plus prednisone in
      men with chemotherapy-naive castration-resistant prostate cancer at the interim
      analyses of the COU-AA-302 trial. Here, we present the prespecified final
      analysis of the trial, assessing the effect of abiraterone acetate plus
      prednisone on overall survival, time to opiate use, and use of other subsequent
      therapies. METHODS: In this placebo-controlled, double-blind, randomised phase 3
      study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive
      prostate cancer stratified by Eastern Cooperative Oncology performance status (0
      vs 1) were randomly assigned with a permuted block allocation scheme via a web
      response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg
      once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or
      placebo plus prednisone (placebo group). Coprimary endpoints were radiographic
      progression-free survival and overall survival analysed in the intention-to-treat
      population. The study is registered with ClinicalTrials.gov, number NCT00887198.
      FINDINGS: At a median follow-up of 49.2 months (IQR 47.0-51.8), 741 (96%) of the
      prespecified 773 death events for the final analysis had been observed: 354 (65%)
      of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the
      placebo group. 238 (44%) patients initially receiving prednisone alone
      subsequently received abiraterone acetate plus prednisone as crossover per
      protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365
      (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo
      group received subsequent treatment with one or more approved agents. Median
      overall survival was significantly longer in the abiraterone acetate group than
      in the placebo group (34.7 months [95% CI 32.7-36.8] vs 30.3 months [28.7-33.3];
      hazard ratio 0.81 [95% CI 0.70-0.93]; p=0.0033). The most common grade 3-4
      adverse events of special interest were cardiac disorders (41 [8%] of 542
      patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the
      placebo group), increased alanine aminotransferase (32 [6%] vs four [<1%]), and
      hypertension (25 [5%] vs 17 [3%]). INTERPRETATION: In this randomised phase 3
      trial with a median follow-up of more than 4 years, treatment with abiraterone
      acetate prolonged overall survival compared with prednisone alone by a margin
      that was both clinically and statistically significant. These results further
      support the favourable safety profile of abiraterone acetate in patients with
      chemotherapy-naive metastatic castration-resistant prostate cancer. FUNDING:
      Janssen Research & Development.

PMID- 25601346
TI  - The rise of Astyanax cavefish.
AB  - Numerous animals have invaded subterranean caverns and evolved remarkably similar
      features. These features include loss of vision and pigmentation, and gains in
      nonvisual sensation. This broad convergence echoes smaller-scale convergence, in
      which members of the same species repeatedly evolve the same cave-associated
      phenotypes. The blind Mexican tetra of the Sierra de El Abra region of
      northeastern Mexico has a complex origin, having recurrently colonized
      subterranean environments through numerous invasions of surface-dwelling fish.
      These colonizations likely occurred ~1-5 MYa. Despite evidence of historical and
      contemporary gene flow between cave and surface forms, the cave-associated
      phenotype appears to remain quite stable in nature. This model system has
      provided insight to the mechanisms of phenotypic regression, the genetic basis
      for constructive trait evolution, and the origin of behavioral novelties. Here,
      we document the rise of this model system from its discovery by a Mexican
      surveyor in 1936, to a powerful system for cave biology and contemporary genetic
      research. The recently sequenced genome provides exciting opportunities for
      future research, and will help resolve several long-standing biological problems.
      Developmental Dynamics 244:1031-1038, 2015. (c) 2015 Wiley Periodicals, Inc.

PMID- 25601348
TI  - Retraction note to: Randomized clinical trial of arginine-supplemented enteral
      nutrition versus standard enteral nutrition in patients undergoing gastric cancer
      surgery.

PMID- 25601349
TI  - Genetics: TTR and HF in black Americans.

PMID- 25601347
TI  - Overexpression of eukaryotic elongation factor 1 alpha-2 is associated with
      poorer prognosis in patients with gastric cancer.
AB  - PURPOSE: Eukaryotic elongation factor 1 alpha-2 (eEF1A2) is a protein translation
      factor involved in protein synthesis. It is overexpressed in various cancers,
      which indicates potential vital functions in tumorigenesis and progression. Our
      study aims to investigate the expression levels of eEF1A2 in gastric cancer and
      its roles in clinical practice. METHODS: A total of 129 patients with
      pathologically confirmed gastric cancer and 24 normal controls were recruited for
      this study. The expression levels of eEF1A2 in gastric cancer and normal tissues
      were evaluated by tissue microarrays, quantitative real-time PCR, and western
      blot analysis. Kaplan-Meier analysis and Cox's proportional hazards model were
      used in survival analysis. RESULTS: Compared with corresponding controls, gastric
      cancer specimens had significantly increased expressions of eEF1A2 at mRNA and
      protein levels (both P < 0.05). Moreover, multivariate analysis confirmed that
      overexpression of eEF1A2 was a significant and independent indicator for
      predicting poor prognosis of gastric cancer. CONCLUSIONS: Our results showed for
      the first time that overexpression of eEF1A2 was correlated with worse outcomes
      in gastric cancer patients, suggesting its critical roles in the carcinogenesis
      of gastric cancer.

PMID- 25601350
TI  - Comparative contraceptive effectiveness of levonorgestrel-releasing and copper
      intrauterine devices: the European Active Surveillance Study for Intrauterine
      Devices.
AB  - OBJECTIVES: The objective was to measure the rate of unintended pregnancies in
      women using levonorgestrel-releasing intrauterine systems (LNG IUSs, releasing 20
      mcg LNG daily) and copper intrauterine devices (IUDs) in a typical population of
      IUD users and to describe associated complications. METHODS: A multinational,
      prospective, non-interventional cohort study of new users of LNG IUS and copper
      IUDs was performed. Following a baseline survey, study participants and their
      physicians completed one follow-up questionnaire after 12 months. A multifaceted
      four-level follow-up procedure minimized loss to follow-up. Patient-reported
      outcomes were validated by the treating physicians. RESULTS: A total of 61,448
      women with a newly inserted IUD were enrolled in six European countries between
      2006 and 2012. The copper IUD cohort contained more than 30 different types.
      Validated 1-year follow-up information for 58,324 users between 18 and 50 years
      of age (70% using LNG IUS, 30% using copper IUDs) was collected. A total of 118
      contraceptive failures occurred (26 LNG, 92 copper). Both types of IUD were
      highly effective, with overall Pearl indices of 0.06 [95% confidence interval
      (CI): 0.04-0.09] and 0.52 (95% CI: 0.42-0.64) for LNG IUS and copper IUDs,
      respectively. The adjusted hazard ratio for LNG IUS vs. copper IUDs was 0.16 (95%
      CI: 0.10-0.25). Tenty-one pregnancies (7 LNG IUS, 14 copper IUD) were ectopic,
      yielding an adjusted hazard ratio for ectopic pregnancy of 0.26 (95% CI: 0.10
      0.66). CONCLUSIONS: The contraceptive failure rate was low with both IUDs.
      However, the LNG IUS was associated with a significantly lower risk of pregnancy,
      including ectopic pregnancy, than the copper IUDs. IMPLICATIONS: To our
      knowledge, this is the first large-scale, multinational, prospective
      epidemiological study to measure and compare the contraceptive effectiveness of
      LNG IUSs and copper IUDs during routine clinical practice. Clinicians and
      patients should be aware of differences in rates of unintended pregnancies and
      associated complications in relation to IUD us.

PMID- 25601351
TI  - The levonorgestrel intrauterine system: cohort study to assess satisfaction in a
      postpartum population in Kenya.
AB  - BACKGROUND: The levonorgestrel intrauterine system (LNG IUS) may become the next
      long-acting contraceptive to be introduced in public sector programs of resource
      poor countries. Whereas service provision for subdermal implants and intrauterine
      devices is growing, little is known about how the LNG IUS might fit in. STUDY
      DESIGN: We conducted a cohort study of 313 women in Kenya who were 6-12 weeks
      postpartum when they started using these methods: subdermal implant (205), LNG
      IUS (93), and copper intrauterine device (15). Participants returned for visits
      at 6 and 12 months to share information on bleeding patterns, side effects,
      satisfaction, and continued use of the products. We used Kaplan-Meier techniques
      to estimate method continuation rates and chi-square tests of association to
      identify differences in experiences with the methods. RESULTS: The 12-month
      continuation rate for the LNG IUS was 89.1 (95% confidence interval [CI] = 86.9
      94.9) and statistically equivalent to that of the subdermal implant (91.8: 95% CI
      = 80.6-94.0). Nearly 87% of LNG IUS users were very satisfied with the method at
      6 months compared to 75% of implant users; this gap closed somewhat at 12 months
      as satisfaction levels of implant users rose. At 12 months 78% of LNG IUS users
      felt that their bleeding pattern was highly acceptable compared with about 66% of
      implant users. CONCLUSIONS: This study found that the LNG IUS compared favorably
      to the subdermal implant in terms of satisfaction levels and continued use. The
      LNG IUS will provide another long-acting option for postpartum women.
      IMPLICATIONS: The LNG IUS may soon be purchased by international donor agencies
      for use in public sector programs in sub-Saharan Africa and other resource-poor
      countries. The results of this study suggest that the product will be successful
      in future introduction activities.

PMID- 25601352
TI  - Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine
      devices in the European Active Surveillance Study on Intrauterine Devices.
AB  - OBJECTIVES: The objectives were to identify and compare the incidence of uterine
      perforation and other medically adverse events associated with levonorgestrel
      releasing intrauterine systems (LNG-IUSs, releasing 20 mcg LNG daily) and copper
      intrauterine devices (IUDs) under routine conditions of use in a study population
      representative of typical users. METHODS AND MATERIALS: This is a multinational,
      prospective, non-interventional cohort study with new users of LNG-IUSs and
      copper IUDs. In addition to a baseline questionnaire, women and their treating
      health care professional completed a single follow-up questionnaire after 12
      months. All patient-reported outcomes were validated by the treating physicians.
      RESULTS: A total of 61,448 women in six European countries were followed between
      2006 and 2013 for more than 68,000 women-years of observation (70% LNG, 30%
      copper devices). Overall, 81 uterine perforations were reported: 61 for LNG-IUSs
      [1.4 per 1000 insertions (95% confidence interval {CI}: 1.1-1.8)] and 20 for
      copper IUDs [1.1 per 1000 insertions (95% CI: 0.7-1.7)], for an adjusted risk
      ratio (RRadj) of 1.6 (95% CI: 1.0-2.7) when adjusted for age, body mass index,
      breastfeeding at time of insertion and parity. Breastfeeding at time of insertion
      was associated with a sixfold increase (RR 6.1, 95% CI: 3.9-9.6), with no
      differences between LNG and copper IUD users. Sixty-three of the total 81
      perforations were associated with previously suspected risk factors (e.g.,
      breastfeeding, time since last delivery <=36 weeks). No perforations led to
      serious illness or to injury of intra-abdominal or pelvic structures.
      CONCLUSIONS: Uterine perforation incidence in this study was low, with a benign
      clinical course thereafter. The LNG-IUSs and copper IUDs did not have clinically
      important differences in perforation rates. IMPLICATIONS: The European Active
      Surveillance Study on Intrauterine Devices is the first large-scale, prospective,
      non-interventional study to compare the perforation risk in LNG-IUS and copper
      IUD users. It is the first to examine the independent roles that breastfeeding
      status and postpartum status have on perforation risk. Conducted during routine
      clinical practice, the findings are generalizable to broader populations.

PMID- 25601353
TI  - Wavelength optimized cross-polarized wide-field imaging for noninvasive and rapid
      evaluation of dermal structures.
AB  - Changes in the morphology of dermal collagen may indicate aging or pathological
      processes. At present, there is no technology for in vivo real-time assessment of
      collagen structures. Our goal was to introduce and validate polarization optical
      imaging for noninvasive quantitative evaluation of dermal collagen. Seventeen
      volunteers participated in the study. Cross-polarized 440 nm images were acquired
      noninvasively from facial skin of the study subjects. Collagen content and
      intensity histogram were computed from the optical images. Quantitative results
      showed a decrease in the collagen content with increasing age of the subjects.
      Analysis of the collagen image histogram parameters demonstrated decreasing mean
      pixel value and increasing full width at half maximum (FWHM) with increasing age.
      Polarization optical imaging has the potential for rapid noninvasive in vivo
      evaluation of human dermis. Cross-polarized imaging at different wavelengths
      emphasizes different features of human skin. (A) Skin photograph. (B) In vivo
      cross-polarized image at 440 nm. (C) In vivo cross-polarized image at 570 nm. (D)
      In vivo cross-polarized image at 690 nm. 

PMID- 25601354
TI  - Seroprevalence and risk factors of Chlamydia abortus infection in free-ranging
      white yaks in China.
AB  - BACKGROUND: Chlamydia is gram-negative obligate bacteria which causes a wide
      variety of diseases in humans and animals. To date, there are a few reports about
      the seroprevalence of Chlamydia and the risk factors associated with Chlamydia
      infection in yaks in the world. In this study, 974 blood samples were collected
      from white yaks (Bos grunniens) in Tianzhu Tibetan Autonomous County, Gansu
      province, northwest China from June 2013 to April 2014. RESULTS: Antibodies
      against Chlamydia abortus were examined by the indirect hemagglutination (IHA)
      test, and 158 of 974 (16.22%) white yaks were seropositive for C. abortus
      antibodies at the cut-off of 1:16. The risk factors associated with
      seroprevalence were evaluated by a multivariate logistic regression analysis.
      Region, gender and age of white yak were left out of the final model, due to its
      insignificance in the logistic regression analysis (P > 0.05). However, season
      was considered as a major risk factor associated with C. abortus infection in
      white yaks. CONCLUSIONS: To our knowledge, this is the first survey of C. abortus
      seroprevalence in white yaks in China, which extends the host range for C.
      abortus and has important implications for public health and the local Tibetan
      economy.

PMID- 25601355
TI  - Homelessness and stakeholders' involvement in the Grand Duchy of Luxembourg: a
      qualitative study.
AB  - BACKGROUND: In 2013, between 150 and 200 people per night in the Grand Duchy of
      Luxembourg are estimated roofless. Abilities to respond to emergencies in the GDL
      are perceptibly decreased due to longer stays in emergency shelters. This study
      aimed to analyse the needs of long-term homeless (LTH) individuals and to put
      forward professional recommendations to improve support and care for homeless
      individuals. METHODS: A local, cross-sectional, qualitative study carried out
      between February and September 2013 in the GDL. Semi-structured interviews and
      focus groups were conducted with homeless people living in Caritas housing
      facilities permanently over a period of 2 years or temporarily over a period of 3
      years, as well as Caritas professionals and Luxembourgish psychiatrists. They
      mainly focused on the homeless person's life pathways, needs and expectations,
      and difficulties encountered. RESULTS: Twenty-two homeless persons, 13
      professionals from Caritas and three Luxembourgish psychiatrists participated.
      Homeless persons' needs and expectations consist of the following: (i) seeking
      freedom and peacefulness, (ii) having their own space, being independent and
      (iii) living like everyone else. Professionals mainly complained about
      difficulties for supporting LTH persons and the lack of collaboration with
      Luxembourg stakeholders from social and psychiatric departments. CONCLUSION: This
      study has found that the current approach is not appropriate for the management
      of LTHness in the country. This study recommends changes within the Caritas
      facilities and outside, on the basis of three concepts: (i) a decent home as an
      essential need, (ii) respect of freedom of choice and (iii) a housing-first
      model.

PMID- 25601356
TI  - Carbon nanotubes part I: preparation of a novel and versatile drug-delivery
      vehicle.
AB  - INTRODUCTION: It is 23 years since carbon allotrope known as carbon nanotubes
      (CNT) was discovered by Iijima, who described them as "rolled graphite sheets
      inserted into each other". Since then, CNTs have been studied in nanoelectronic
      devices. However, CNTs also possess the versatility to act as drug- and gene
      delivery vehicles. AREAS COVERED: This review covers the synthesis, purification
      and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor
      deposition are the principle synthesis methods. Non-covalent functionalization
      relies on attachment of biomolecules by coating the CNT with surfactants,
      synthetic polymers and biopolymers. Covalent functionalization often involves the
      initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3
      dipolar cycloaddition or reductive alkylation. The aim is to produce functional
      groups to attach the active cargo. EXPERT OPINION: In this review, the
      feasibility of CNT being used as a drug-delivery vehicle is explored. The
      molecular composition of CNT is extremely hydrophobic and highly aggregation
      prone. Therefore, most of the efforts towards drug delivery has centered on
      chemical functionalization, which is usually divided in two categories; non
      covalent and covalent. The biomedical applications of CNT are growing apace, and
      new drug-delivery technologies play a major role in these efforts.

PMID- 25601357
TI  - Renal denervation in treatment-resistant hypertension: a reappraisal.
AB  - The Symplicity HTN-1 and 2 studies proposed renal denervation (RDN) as an
      effective and safe approach to treat patients with resistant hypertension, and
      were followed by an unprecedented wave of enthusiasm. The announcement that
      Symplicity HTN-3 failed to meet its primary efficacy endpoint put an abrupt stop
      to these overoptimistic expectations. The use of a sound methodology was enough
      to see the typical 25-30mmHg systolic blood pressure decrease observed after RDN
      melt down to <3mmHg. RDN certainly deserves further investigation but is not
      ready for wide clinical application. For the time being, physicians should focus
      on improvement of drug adherence and skilful drug treatment adjustment, which
      allow reaching blood pressure target in the large majority of hypertensive
      patients. 

PMID- 25601358
TI  - The impact of foot ulceration and amputation on mortality in diabetic patients.
      I: From ulceration to death, a systematic review.
AB  - A great deal of emphasis, clinical and financial, is placed on limb salvage
      efforts in diabetic patients suffering from lower extremity ulceration. This is
      because of the impression that amputation in such patients may be a proximal
      cause of death. While amputation is certainly a negative clinical outcome, it is
      not entirely clear that it causes death. In this systematic review, we examine
      the available literature to attempt to understand the role that the ulceration
      itself may play in mortality. In brief, we searched for human studies in OVID,
      CINAHL and the COCHRANE CENTRAL DATABASE from 1980 to 2013, looking for articles
      related to ulcer or wound of the foot, in patients with diabetes or peripheral
      vascular disease, and death. We looked for articles with 5 years of follow-up, or
      Kaplan-Meier estimates of 5-year mortality, and excluded reviews and letters.
      Articles were assessed for quality and potential bias using the Newcastle-Ottawa
      scale. We find that while the patient populations studied varied widely in terms
      of demographics and comorbidities, limiting generalisability, 5-year mortality
      rates after ulceration were around 40%. Risk factors for death commonly
      identified were increased age, male gender, peripheral vascular disease and renal
      disease. 

PMID- 25601359
TI  - Comment on "Contaminant levels in Norwegian farmed Atlantic salmon (Salmo salar)
      in the 13-year period from 1999 to 2011" by Nostbakken et al.

PMID- 25601360
TI  - Nacre-mimetics with synthetic nanoclays up to ultrahigh aspect ratios.
AB  - Nacre-mimetics hold great promise as mechanical high-performance and functional
      materials. Here we demonstrate large progress of mechanical and functional
      properties of self-assembled polymer/nanoclay nacre-mimetics by using synthetic
      nanoclays with aspect ratios covering three orders in magnitude (25-3,500). We
      establish comprehensive relationships among structure formation,
      nanostructuration, deformation mechanisms and mechanical properties as a function
      of nanoclay aspect ratio, and by tuning the viscoelastic properties of the soft
      phase via hydration. Highly ordered, large-scale nacre-mimetics are obtained even
      for low aspect ratio nanoplatelets and show pronounced inelastic deformation with
      very high toughness, while those formed by ultralarge nanoplatelets exhibit
      superb stiffness and strength, previously only reachable for highly crosslinked
      materials. Regarding functionalities, we report formerly impossible glass-like
      transparency, and excellent gas barrier considerably exceeding earlier nacre
      mimetics based on natural nanoclay. Our study enables rational design of future
      high-performance nacre-mimetic materials and opens avenues for ecofriendly,
      transparent, self-standing and strong advanced barrier materials. 

PMID- 25601361
TI  - Increased postural sway predicts negative symptom progression in youth at
      ultrahigh risk for psychosis.
AB  - Impaired ability to maintain an upright posture may reflect impairment in the
      cerebellum, a critical structure for the fluid coordination of neural
      information, thought to be disrupted in psychosis. The current study utilized an
      instrumental measure of posture in individuals at ultrahigh risk (UHR) for
      psychosis (n=43) and healthy controls (n=44). Positive and negative symptoms were
      assessed twice over 12months. Results showed that increased postural sway in the
      UHR group predicted changes in negative symptoms. This study provides an
      important prospective view on the relationship between cerebellar-sensitive
      behavior and integral symptoms, which until now has received limited biomarker
      research. 

PMID- 25601363
TI  - Social jetlag, obesity and metabolic disorder: investigation in a cohort study.
AB  - BACKGROUND: Obesity is one of the leading causes of preventable death worldwide.
      Circadian rhythms are known to control both sleep timing and energy homeostasis,
      and disruptions in circadian rhythms have been linked with metabolic dysfunction
      and obesity-associated disease. In previous research, social jetlag, a measure of
      chronic circadian disruption caused by the discrepancy between our internal
      versus social clocks, was associated with elevated self-reported body mass index,
      possibly indicative of a more generalized association with obesity and metabolic
      dysfunction. METHODS: We studied participants from the population-representative
      Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was
      associated with clinically assessed measurements of metabolic phenotypes and
      disease indicators for obesity-related disease, specifically, indicators of
      inflammation and diabetes. RESULTS: Our analysis was restricted to N=815 non
      shift workers in our cohort. Among these participants, we found that social
      jetlag was associated with numerous clinically assessed measures of metabolic
      dysfunction and obesity. We distinguished between obese individuals who were
      metabolically healthy versus unhealthy, and found higher social jetlag levels in
      metabolically unhealthy obese individuals. Among metabolically unhealthy obese
      individuals, social jetlag was additionally associated with elevated glycated
      hemoglobin and an indicator of inflammation. CONCLUSIONS: The findings are
      consistent with the possibility that 'living against our internal clock' may
      contribute to metabolic dysfunction and its consequences. Further research aimed
      at understanding that the physiology and social features of social jetlag may
      inform obesity prevention and have ramifications for policies and practices that
      contribute to increased social jetlag, such as work schedules and daylight
      savings time.

PMID- 25601364
TI  - Spin pumping in ferromagnet-topological insulator-ferromagnet heterostructures.
AB  - Topological insulators (TIs) are enticing prospects for the future of spintronics
      due to their large spin-orbit coupling and dissipationless, counter-propagating
      conduction channels in the surface state. However, a means to interact with and
      exploit the topological surface state remains elusive. Here, we report a study of
      spin pumping at the TI-ferromagnet interface, investigating spin transfer
      dynamics in a spin-valve like structure using element specific time-resolved x
      ray magnetic circular dichroism, and ferromagnetic resonance. Gilbert damping
      increases approximately linearly with increasing TI thickness, indicating
      efficient behaviour as a spin sink. However, layer-resolved measurements suggest
      that a dynamic coupling is limited. These results shed new light on the spin
      dynamics of this novel material class, and suggest great potential for TIs in
      spintronic devices, through their novel magnetodynamics that persist even up to
      room temperature. 

PMID- 25601362
TI  - Losing the sugar coating: potential impact of perineuronal net abnormalities on
      interneurons in schizophrenia.
AB  - Perineuronal nets (PNNs) were shown to be markedly altered in subjects with
      schizophrenia. In particular, decreases of PNNs have been detected in the
      amygdala, entorhinal cortex and prefrontal cortex. The formation of these
      specialized extracellular matrix (ECM) aggregates during postnatal development,
      their functions, and association with distinct populations of GABAergic
      interneurons, bear great relevance to the pathophysiology of schizophrenia. PNNs
      gradually mature in an experience-dependent manner during late stages of
      postnatal development, overlapping with the prodromal period/age of onset of
      schizophrenia. Throughout adulthood, PNNs regulate neuronal properties, including
      synaptic remodeling, cell membrane compartmentalization and subsequent regulation
      of glutamate receptors and calcium channels, and susceptibility to oxidative
      stress. With the present paper, we discuss evidence for PNN abnormalities in
      schizophrenia, the potential functional impact of such abnormalities on
      inhibitory circuits and, in turn, cognitive and emotion processing. We integrate
      these considerations with results from recent genetic studies showing genetic
      susceptibility for schizophrenia associated with genes encoding for PNN
      components, matrix-regulating molecules and immune system factors. Notably, the
      composition of PNNs is regulated dynamically in response to factors such as fear,
      reward, stress, and immune response. This regulation occurs through families of
      matrix metalloproteinases that cleave ECM components, altering their functions
      and affecting plasticity. Several metalloproteinases have been proposed as
      vulnerability factors for schizophrenia. We speculate that the physiological
      process of PNN remodeling may be disrupted in schizophrenia as a result of
      interactions between matrix remodeling processes and immune system dysregulation.
      In turn, these mechanisms may contribute to the dysfunction of GABAergic neurons.

PMID- 25601366
TI  - Laparoscopic cholecystectomy: evaluation of liver function tests.
AB  - AIM: The changes in liver function tests (LFTs) after laparoscopic
      cholecystectomy (LC) have been described in the literature. The aims of this
      study are to value the increases of the LFTs and its clinical appearance after
      LC. Furthermore we studied the correlation of the changes of LFTs with the
      operative time and the role of elevated BMI. MATERIAL OF STUDY: In the period
      October 2012 - May 2013, 81 patients undergone to elective LC were analyzed by
      examining bilirubin, AST, ALT, ALP, GGT at the admission, 1 and 3 days after
      surgery. Correlations of the length of intervention and BMI with changes of LFTs
      are evaluated. During surgery, the intrabdominal pressure has been 12 mmHg in all
      patients. The Student t test, PCC (Pearson's correlation coefficient) OR (odds
      ratio) were performed to determine statistical significance. RESULTS: The level
      of (serum) AST, ALT increased significantly during 24-48 hours after LC (p <
      0,0001). The increase of (total and direct) bilirubin has not the statistical
      significance. On the contrary ALP, GGT was significantly decreased (p < 0,001).
      Three days after surgery LFTs returned to normal level in the patients with
      previous normal level of tests. The length of intervention doesn't show
      correlations with changes of LFTs (PCC 0.2). the BMI >28 led increased risk of
      changes of LFTs (OR 2.44). CONCLUSIONS: The changes of LFTs are transient and
      clinically silent in patients with a normal liver function. Nevertheless must be
      evaluated preoperative BMI and liver dysfunction.

PMID- 25601365
TI  - Discontinuation of buprenorphine maintenance therapy: perspectives and outcomes.
AB  - Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid
      maintenance agent due to its reduced toxicity and availability in an office-based
      setting in the United States. Although BMT has been shown to be highly
      efficacious, it is often discontinued soon after initiation. No current
      systematic review has yet investigated providers' or patients' reasons for BMT
      discontinuation or the outcomes that follow. Hence, provider and patient
      perspectives associated with BMT discontinuation after a period of stable
      buprenorphine maintenance and the resultant outcomes were systematically reviewed
      with specific emphasis on pre-buprenorphine-taper parameters predictive of
      relapse following BMT discontinuation. Few identified studies address provider or
      patient perspectives associated with buprenorphine discontinuation. Within the
      studies reviewed providers with residency training in BMT were more likely to
      favor long term BMT instead of detoxification, and providers were likely to
      consider BMT discontinuation in the face of medication misuse. Patients often
      desired to remain on BMT because of fear of relapse to illicit opioid use if they
      were to discontinue BMT. The majority of patients who discontinued BMT did so
      involuntarily, often due to failure to follow strict program requirements, and 1
      month following discontinuation, rates of relapse to illicit opioid use exceeded
      50% in every study reviewed. Only lower buprenorphine maintenance dose, which may
      be a marker for attenuated addiction severity, predicted better outcomes across
      studies. Relaxed BMT program requirements and frequent counsel on the high
      probability of relapse if BMT is discontinued may improve retention in treatment
      and prevent the relapse to illicit opioid use that is likely to follow BMT
      discontinuation.

PMID- 25601371
TI  - Study of phenanthrene utilizing bacterial consortia associated with cowpea (Vigna
      unguiculata) root nodules.
AB  - Many legumes have been selected as model plants to degrade organic contaminants
      with their special associated rhizosphere microbes in soil. However, the function
      of root nodules during microbe-assisted phytoremediation is not clear. A pot
      study was conducted to examine phenanthrene (PHE) utilizing bacteria associated
      with root nodules and the effects of cowpea root nodules on phytoremediation in
      two different types of soils (freshly contaminated soil and aged contaminated
      soil). Cowpea nodules in freshly-contaminated soil showed less damage in
      comparison to the aged-contaminated soil, both morphologically and ultra
      structurally by scanning electron microscopy. The study of polycyclic aromatic
      hydrocarbon (PAH) attenuation conducted by high performance liquid chromatography
      revealed that more PAH was eliminated from liquid culture around nodulated roots
      than nodule-free roots. PAH sublimation and denaturation gradient gel
      electrophoresis were applied to analyze the capability and diversity of PAH
      degrading bacteria from the following four parts of rhizo-microzone: bulk soil,
      root surface, nodule surface and nodule inside. The results indicated that the
      surface and inside of cowpea root nodules were colonized with bacterial consortia
      that utilized PHE. Our results demonstrated that root nodules not only fixed
      nitrogen, but also enriched PAH-utilizing microorganisms both inside and outside
      of the nodules. Legume nodules may have biotechnological values for PAH
      degradation. 

PMID- 25601372
TI  - [Place of persistence trouble during oral contraception and subsequent use of
      emergency contraception].
AB  - OBJECTIVE: In order to improve the understanding of hormonal contraceptive
      failures, this study evaluates the persistence of oral contraception and the use
      of emergency contraception (EC) during persistence incidents. We made the
      hypothesis of the existence of a strong link between the risk of unplanned
      pregnancies and these two parameters. In this study, we also evaluated women's
      perception of EC in order to elucidate the reasons of EC insufficient use.
      METHODS: One survey was carried out on Internet on a representative sample of
      women, aged 16-45. RESULTS: In this survey, 3775 French women were interviewed
      (source-population). We defined a target population of 2415 fertile women who had
      heterosexual intercourse during the last 12 months, and a population of 760 women
      at risk of unintended pregnancy who had unprotected sexual intercourse during the
      last 12 months(risk-population). A little more than 30% of the target population,
      meaning 20% of the source-population (n=745) stopped their contraceptive method
      temporarily for an average time of two months. Almost 60% of women had a risk of
      unwanted pregnancy during this period without contraception, which is 59% of the
      risk-population. Only 20% of women among the population at risk used EC. The main
      reasons given for EC insufficient use were the misperception of the risk of
      pregnancy, the lack of knowledge about EC and its way of use. CONCLUSION: For the
      first time, this survey shows that 13% of women (of the source population) decide
      to stop temporarily their contraceptive method for an average time of two months
      per year. Fifty-nine percent of unplanned pregnancy situations are due to this
      poor contraception persistence. Although there is a need to reduce the risk of
      women being at risk, it seems also highly desirable to overcome the consequences
      of this poor persistence. Giving information about EC and a systematic
      prescription during contraception consultations would lead to an increased use of
      EC.

PMID- 25601373
TI  - [Small birth weights and weight of words].

PMID- 25601379
TI  - Reply: To PMID 24954263.

PMID- 25601374
TI  - Indoor fungi: companions and contaminants.
AB  - This review discusses the role of fungi and fungal products in indoor
      environments, especially as agents of human exposure. Fungi are present
      everywhere, and knowledge for indoor environments is extensive on their
      occurrence and ecology, concentrations, and determinants. Problems of dampness
      and mold have dominated the discussion on indoor fungi. However, the role of
      fungi in human health is still not well understood. In this review, we take a
      look back to integrate what cultivation-based research has taught us alongside
      more recent work with cultivation-independent techniques. We attempt to summarize
      what is known today and to point out where more data is needed for risk
      assessment associated with indoor fungal exposures. New data have demonstrated
      qualitative and quantitative richness of fungal material inside and outside
      buildings. Research on mycotoxins shows that just as microbes are everywhere in
      our indoor environments, so too are their metabolic products. Assessment of
      fungal exposures is notoriously challenging due to the numerous factors that
      contribute to the variation of fungal concentrations in indoor environments. We
      also may have to acknowledge and incorporate into our understanding the
      complexity of interactions between multiple biological agents in assessing their
      effects on human health and well-being. 

PMID- 25601380
TI  - Occupational asthma is a cause of adult-onset asthma with poor prognosis.

PMID- 25601381
TI  - Neuropsychological differences between obsessive-compulsive washers and checkers:
      a systematic review and meta-analysis.
AB  - Inconsistent results in neuropsychological research of obsessive-compulsive
      disorder (OCD) may be the result of the heterogeneous nature of OCD symptoms. The
      most frequently investigated symptoms are contamination/cleaning and
      doubt/checking. The aim of this review was to determine whether OCD washers and
      checkers differ in their neuropsychological performance. We conducted a meta
      analysis of 13 studies (including 535 patients) comprising tests in 10 different
      neuropsychological domains. Washers showed significant better task performance
      than checkers in 8 of 10 cognitive domains. Large effect sizes were found in
      planning/problem solving and response inhibition. Effect size in set shifting was
      medium, whereas effect sizes in attention, processing speed, encoding, verbal
      memory and nonverbal memory were small. Limitations consisted in a relatively
      small number of primary studies. In line with current neurobiological findings,
      the results provide further evidence for the validity of different symptom
      dimensions in OCD. Clinical and theoretical implications are discussed. 

PMID- 25601382
TI  - The effects of progressive lateralization of the joint center of rotation of
      reverse total shoulder implants.
AB  - BACKGROUND: There has been a renewed interest in lateralizing the center of
      rotation (CoR) in implants used in reverse shoulder arthroplasty. The aim of this
      study was to determine the sensitivity of lateralization of the CoR on the
      glenohumeral joint contact forces, muscle moment arms, torque across the bone
      implant interface, and the stability of the implant. METHODS: A 3-dimensional
      virtual model was used to investigate how lateralization affects deltoid muscle
      moment arm and glenohumeral joint contact forces. This model was virtually
      implanted with 5 progressively lateralized reverse shoulder prostheses. The joint
      contact loads and deltoid moment arms were calculated for each lateralization
      over the course of 3 simulated standard humerothoracic motions. RESULTS:
      Lateralization of the CoR leads to an increase in the overall joint contact
      forces across the glenosphere. Most of this increased loading occurred through
      compression, although increases in anterior/posterior and superior/inferior shear
      were also observed. Moment arms of the deltoid consistently decreased with
      lateralization. Bending moments at the implant interface increased with
      lateralization. Progressive lateralization resulted in improved stability ratios.
      CONCLUSIONS: Lateralization results in increased joint loading. Most of that
      loading occurs through compression, although there were also increases in shear
      forces. Anterior/posterior shear is currently not accounted for in implant
      fixation studies, leaving its effect on implant fixation unknown. Future studies
      should incorporate shear forces into their models to more accurately assess
      fixation methods.

PMID- 25601383
TI  - Surface replacement arthroplasty for glenohumeral arthropathy in patients aged
      younger than fifty years: results after a minimum ten-year follow-up.
AB  - BACKGROUND: The role of cementless surface replacement arthroplasty (CSRA) in
      young individuals is currently unclear. The aim of this study was to evaluate
      CSRA long-term results for glenohumeral arthritis in young patients. METHODS:
      Between 1990 and 2003, 54 CSRAs were performed on 49 patients (25 men, 24 women)
      aged younger than 50 years. Mean age was 38.9 years (range, 22-50 years). Three
      patients (4 shoulders) died over time and 8 were lost to follow-up, leaving 38
      patients (42 shoulders) with a mean follow-up of 14.5 years (range, 10-25 years).
      There were 17 total shoulder replacements with metal back glenoid, and 37
      underwent humeral head resurfacing with microfracture of the glenoid. RESULTS:
      The indications were avascular necrosis, 16; rheumatoid arthritis, 20;
      instability arthropathy, 7; primary osteoarthritis, 5; fracture sequelae, 3;
      postinfection arthritis, 2; and psoriatic arthritis, 1. The mean relative
      Constant score increased from 11.5% to 71.8% (P < .0001), and the mean patient
      satisfaction at final follow-up was 8.7 of 10. The mean relative Constant score
      for the humeral head resurfacing with microfracture of the glenoid improved to
      77.7% compared with 58.1% for total resurfacing arthroplasty. Two required early
      arthrodesis due to instability and deep infection. Seven were revised to stemmed
      prosthesis: 1 for traumatic fracture and 1 for glenoid erosion 16 years after the
      index procedure. Five shoulders in 4 patients (4 rheumatoid arthritis, 1
      avascular necrosis) were revised at 8 to 14 years after surgery for cuff failure
      and loosening. Three were revised to stemless reverse total shoulder arthroplasty
      due to rotator cuff failure at 23, 16, and 13 years after surgery. CONCLUSIONS:
      CSRA provides good long-term symptomatic and functional results in the treatment
      of glenohumeral arthropathy in patients aged younger than 50 years in 81.6% of
      the patients. This improvement is maintained over more than 10 years after
      surgery, with high patient satisfaction (8.7 of 10). However, 10 shoulders (of
      54) (18.5%) underwent revision arthroplasty. Resurfacing offers a valuable tool
      in treating young patients with glenohumeral arthritis, providing reasonably good
      long-term results in 81.6% of the patients, while allowing preservation of bone
      stock if the need for revision arises. All the revision arthroplasty options are
      preserved, including less invasive procedures.

PMID- 25601384
TI  - Heterotopic ossification formation after fracture-dislocations of the elbow.
AB  - BACKGROUND: Heterotopic ossification (HO) is a serious complication of traumatic
      elbow injuries, particularly fracture-dislocations. Limited data exist in the
      literature regarding the risk factors associated with HO formation in these
      injuries. The purpose of this study was to review the incidence of HO after
      fracture-dislocation of the elbow and to identify potential risk factors
      associated with its formation. METHODS: Twenty-seven patients (28 elbows) were
      surgically treated for elbow fracture-dislocations during 8 years, with an
      average follow-up of 14 months. Records were reviewed with attention paid to
      several factors: demographic data, comorbidities, time interval from injury to
      surgical intervention, number of closed reductions attempted before surgery,
      surgical approach, management of the radial head, treatment of the anterior
      capsular injury, and coronoid fixation. RESULTS: Of the 28 elbows, 12 (43%)
      developed HO postoperatively; 9 of 28 elbows underwent multiple attempted closed
      reductions before definitive surgical stabilization, with HO formation in 7 of
      the 9 (77%). Time to surgery, age, gender, radial head fixation or replacement,
      coronoid open reduction and internal fixation, capsular repair, and medical
      comorbidities were not found to influence HO formation, although the performance
      of multiple reductions was identified as a risk factor. DISCUSSION: HO developed
      in 77% of patients with multiple attempted closed reductions. We found a 43%
      incidence of HO in patients surgically treated for elbow fracture-dislocations.
      Neither time to surgery after the injury nor demographic or other factors
      relating to the manner in which associated osseous or soft tissue injuries were
      managed influenced the formation of HO.

PMID- 25601386
TI  - Treatment of a suspension of PCB contaminated soil using iron nanoparticles and
      electric current.
AB  - Contaminated soils and sediments with polychlorinated biphenyls (PCB) are an
      important environmental problem due to the persistence of these synthetic
      aromatic compounds and to the lack of a cost-effective and sustainable
      remediation technology. Recently, a new experimental setup has been proposed
      using electrodialytic remediation and iron nanoparticles. The current work
      compares the performance of this new setup (A) with conventional electrokinetics
      (setup B). An historically contaminated soil with an initial PCB concentration of
      258 MUg kg(-1) was treated during 5, 10, 20 and 45 d using different amounts of
      iron nanoparticles in both setups A and B. A PCB removal of 83% was obtained in
      setup A compared with 58% of setup B. Setup A also showed additional advantages,
      such as a higher PCB dechlorination, in a shorter time, with lower nZVI
      consumption, and with the use of half of the voltage gradient when compared with
      the traditional setup (B). Energy and nZVI costs for a full-scale reactor are
      estimated at 72 ? for each cubic meter of PCB contaminated soil treated on-site,
      making this technology competitive when compared with average off-site
      incineration (885 ? m(-3)) or landfilling (231 ? m(-3)) cost in Europe and in the
      USA (327 USD m(-3)).

PMID- 25601385
TI  - Checkpoint-dependent RNR induction promotes fork restart after replicative
      stress.
AB  - The checkpoint kinase Rad53 is crucial to regulate DNA replication in the
      presence of replicative stress. Under conditions that interfere with the
      progression of replication forks, Rad53 prevents Exo1-dependent fork degradation.
      However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does
      not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor
      hydroxyurea (HU). In this case, the inability to restart stalled forks is likely
      to account for the lethality of rad53 mutant cells after replication blocks. Here
      we show that Rad53 regulates replication restart through the checkpoint-dependent
      transcriptional response, and more specifically, through RNR induction. Thus, in
      addition to preventing fork degradation, Rad53 prevents cell death in the
      presence of HU by regulating RNR-expression and localization. When RNR is induced
      in the absence of Exo1 and RNR negative regulators, cell viability of rad53
      mutants treated with HU is increased and the ability of replication forks to
      restart after replicative stress is restored. 

PMID- 25601387
TI  - Effect of Psychosocial Skills Training on Disease Symptoms, Insight, Internalized
      Stigmatization, and Social Functioning in Patients with Schizophrenia.
AB  - PURPOSE: This study was performed for the purpose of determining the effect of
      psychosocial skills training (PSST) on disease symptoms, insight, internalized
      stigmatization, and social functioning in patients with schizophrenia. DESIGN:
      One group pretest-posttest model. METHOD: The study was carried out with 25
      outpatients who were diagnosed with schizophrenia. The PSST was given to three
      groups of eight to nine patients once a week in 24 sessions, each lasting 90-120
      minutes for a period of 6 months. FINDINGS: The program had significant results
      in schizophrenic patients in improving the level of symptoms, increasing the
      level of functioning, and coping with stigmatization. CONCLUSION: The PSST
      program, adjuvant to pharmacological treatments, can be considered as a
      significant modality in daily practice due to its effect on improving symptoms,
      insight, and level of functioning and decreasing internalized stigmatization.
      CLINICAL RELEVANCES: PSST in patients with schizophrenia can contribute to the
      use of evidence-based education strategies in psychiatric nursing practice to
      improve coping skills with the disease.

PMID- 25601388
TI  - Photophysical and quantum chemical studies on the interactions of oxazine-1 dye
      with cucurbituril macrocycles.
AB  - Supramolecular host-guest interaction of cationic oxazine-1 (OX1) dye with two
      cucurbit[n]uril (CBn) hosts, namely, CB7 and CB8, has been investigated using
      photophysical and quantum chemical studies. Both CB7 and CB8 display much
      stronger binding affinities for OX1 dye compared to conventional cyclodextrin
      (CD) hosts, which arises due to strong ion-dipole interaction in stabilizing the
      dye-host inclusion complexes in the present systems. From photophysical studies
      supported by (1)H NMR results and quantum chemical calculations, it is inferred
      that 1:1 inclusion complexes are mainly formed in the present systems, though a
      small percentage of 1:2 (dye.host2) complexes are also indicated from time
      resolved (TR) fluorescence studies. Longer rotational relaxation times for dye
      CBn systems compared to the free dye as estimated from TR anisotropy studies
      support the inclusion complex formation in the present systems. The binding
      constant value is estimated to be significantly higher for the OX1-CB7 system
      than the OX1-CB8 system, and these results are in accordance with compatible
      portal diameter of CB7 cavity compared to the much larger portal diameter of CB8
      cavity relative to the width of the OX1 molecule. Accordingly, CB7 cavity renders
      a relatively stronger binding than the CB8 cavity for an axially incorporated OX1
      dye into the host cavity. Results from the quantum chemical calculations are
      overall supportive to the inferences drawn from photophysical measurements.
      Observed results clearly suggest that the dimensions of the CBn cavities play an
      important role in determining the interaction strength and stoichiometry of the
      host-guest complexes formed and thus bring out significant changes in the
      photophysical properties of the bound dye. The host-assisted modulation in the
      photophysical properties of the dye, as observed in the present study, has a
      direct relevance to applications like aqueous dye lasers, sensors, fluorescence
      assays, and so on. 

PMID- 25601390
TI  - The dopamine D3 receptor regulates the effects of methamphetamine on LPS-induced
      cytokine production in murine mast cells.
AB  - Previous studies have demonstrated that methamphetamine (METH) alter inflammatory
      and anti-inflammatory cytokine production in the periphery. However, the effect
      of METH on lipopolysaccharide (LPS)-induced immune responses and its underlying
      mechanism of action remains unclear. The dopamine D3 receptor (D3R) plays an
      important role in METH addiction, indicating that the D3R may regulate METH
      mediated immune responses. In this study, we examined the effect of METH on mast
      cell released cytokines in the lungs and thymi of mice stimulated by LPS, and on
      LPS-induced murine bone marrow-derived mast cells (BMMCs). Moreover, we used D3R
      deficient mice to investigate the effect of this receptor on LPS-stimulated mast
      cell released cytokine production after METH treatment in the lungs and thymi.
      The effects of a D3R agonist and antagonist on LPS-induced cytokine production
      after METH treatment in murine BMMCs were also evaluated. METH suppressed LPS
      induced cytokine production in the lungs and thymi of wild-type (WT) mice and
      BMMCs. However, METH did not alter LPS-induced cytokine production in the lungs
      and thymi of D3R-deficient mice. When BMMCs were treated with the D3R receptor
      antagonist, NGB2904 hydrochloride (NGB-2904), METH did not alter LPS-induced
      cytokine production. However, treatment with the D3R agonist, 7-hydroxy-(di-n
      propylamino) tetralin (7-OH-DPAT), significantly enhanced the effects of METH on
      LPS-induced cytokine production. Our results suggest that METH regulates mast
      cell released cytokines production in an LPS-induced mouse model via the D3R. 

PMID- 25601389
TI  - Depressive Symptoms Among Older Adults Who Do Not Drive: Association With
      Mobility Resources and Perceived Transportation Barriers.
AB  - PURPOSE OF THE STUDY: To examine alternative means of mobility that nondriving
      older adults rely on and their impact on well-being. DESIGN AND METHODS: Data
      from the 2011 (T1, N = 6,680) and 2012 (T2, N = 5,413) interview waves of the
      National Health and Aging Trends Study were used to examine sample
      characteristics by driving status, use of alternative mobility resources, and
      perceived transportation-related barriers among ex-drivers and nondrivers, and
      their association with depressive symptoms. RESULTS: A majority of nondrivers
      relied on their informal support system and/or paid assistance to drive them to
      places. About half reported walking/using a wheelchair or scooter. A significant
      proportion of never drivers also used public transportation and van/shuttle
      services, whereas a smaller proportion of ex-drivers used them. Nondrivers who
      walked for transport had lower depressive symptoms than those who did not walk at
      either T1 or T2, and perception of transportation barriers to visiting
      friends/family was associated with higher depressive symptoms at T1 only.
      IMPLICATIONS: Older adults' mobility needs should be met through increasing
      walkability, public and paratransit transportation, supplemental senior
      transportation, and increasing informal caregivers-transportation providers'
      ability to aid older adults.

PMID- 25601391
TI  - Escherichia coli maltose-binding protein (MBP) directly induces mouse Th1
      activation through upregulating TLR2 and downregulating TLR4 expressions.
AB  - Maltose-binding protein (MBP), a component of the maltose transport system of
      Escherichia coli, has been commonly thought to have minimal bioactivity. Our
      previous studies demonstrated that MBP could significantly enhance Bacillus
      Calmette-Guerin (BCG)-induced T helper 1 (Th1) cell activation in mice. In the
      present study, we analyzed the effect of MBP on mouse T cells and found that MBP
      promoted the proliferation and IFN-gamma production of CD4(+) T cells, suggesting
      that MBP directly induces Th1 activation. To explore the mechanism of Th1
      activation, the expression of Toll-like receptor 2/4 (TLR2/4) on purified mouse
      CD4(+) T cells was detected. The results showed that MBP up-regulated TLR2 while
      down-regulated TLR4 expression, accompanied by a clear increase in MyD88
      expression and IkappaB phosphorylation. Notably, the addition of anti-TLR2
      antibody abrogated the MBP-induced CD4(+) T cells proliferation, IFN-gamma
      secretion and MyD88 expression, whereas the addition of anti-TLR4 antibody
      exhibited a contradictive effect. Besides, the block of either TLR2 or TLR4 both
      reduced IkappaB phosphorylation. These results above suggest that TLR2-mediated
      MyD88-dependent pathway contributes to MBP-induced Th1 activation, while TLR4
      appears to counteract this effect via MyD88-independent pathway. 

PMID- 25601392
TI  - Zinc transporter found attached to N-methyl-D-aspartate receptors.

PMID- 25601394
TI  - Effect of repetition duration during resistance training on muscle hypertrophy: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Maximizing the hypertrophic response to resistance training (RT) is
      thought to be best achieved by proper manipulation of exercise program variables
      including exercise selection, exercise order, length of rest intervals, intensity
      of maximal load, and training volume. An often overlooked variable that also may
      impact muscle growth is repetition duration. Duration amounts to the sum total of
      the concentric, eccentric, and isometric components of a repetition, and is
      predicated on the tempo at which the repetition is performed. OBJECTIVE: We
      conducted a systematic review and meta-analysis to determine whether alterations
      in repetition duration can amplify the hypertrophic response to RT. METHODS:
      Studies were deemed eligible for inclusion if they met the following criteria:
      (1) were an experimental trial published in an English-language refereed journal;
      (2) directly compared different training tempos in dynamic exercise using both
      concentric and eccentric repetitions; (3) measured morphologic changes via
      biopsy, imaging, and/or densitometry; (4) had a minimum duration of 6 weeks; (5)
      carried out training to muscle failure, defined as the inability to complete
      another concentric repetition while maintaining proper form; and (6) used human
      subjects who did not have a chronic disease or injury. A total of eight studies
      were identified that investigated repetition duration in accordance with the
      criteria outlined. RESULTS: Results indicate that hypertrophic outcomes are
      similar when training with repetition durations ranging from 0.5 to 8 s.
      CONCLUSIONS: From a practical standpoint it would seem that a fairly wide range
      of repetition durations can be employed if the primary goal is to maximize muscle
      growth. Findings suggest that training at volitionally very slow durations (>10s
      per repetition) is inferior from a hypertrophy standpoint, although a lack of
      controlled studies on the topic makes it difficult to draw definitive
      conclusions.

PMID- 25601395
TI  - Role of endocannabinoid signalling in the dorsolateral periaqueductal grey in the
      modulation of distinct panic-like responses.
AB  - Panic attacks, a major feature of panic disorder, can be modelled in rats by
      exposing animals to stimuli that induce escape reactions, such as the elevated T
      maze or the activation of the dorsolateral periaqueductal grey. Since the
      cannabinoid CB1 receptor modulates various types of aversive responses, this
      study tested the hypothesis that enhancement of endocannabinoid signalling in the
      dorsolateral periaqueductal grey inhibits panic-like reactions in rats. Local
      injection of the CB1 agonist, arachidonoyl 2-Chloroethylamide (0.005-0.5 pmol),
      attenuated the escape response from the open arm of the elevated T-maze, a
      panicolytic effect. The anandamide hydrolysis inhibitor, URB597 (0.3-3 nmol), did
      not induce consistent results. In the test of dorsolateral periaqueductal grey
      stimulation with d,l-homocysteic acid, arachidonoyl 2-Chloroethylamide, at the
      lowest dose, attenuated the escape reaction. The highest dose of URB597 also
      inhibited this response, contrary to the result obtained in the elevated T-maze.
      This effect was reversed by the CB1 antagonist, AM251 (100 pmol). The present
      results confirm the anti-aversive property of direct CB1 receptor activation in
      the dorsolateral periaqueductal grey. The effect of the anandamide hydrolysis
      inhibitor, however, could be detected only in a model employing direct
      stimulation of this structure. Altogether, these results suggest that anandamide
      signalling is recruited only under certain types of aversive stimuli. 

PMID- 25601397
TI  - Healthy diet markedly reduces type 2 diabetes risk in ethnic minority women,
      study finds.

PMID- 25601396
TI  - Schizophrenia biomarkers: translating the descriptive into the diagnostic.
AB  - While schizophrenia and mental health are qualitatively distinct at the level of
      clinical presentation, the specific molecular signatures that underlie, or
      associate with, illness are not. Biomarker identification in schizophrenia is
      intended to offer a number of important benefits to patient well-being including
      prediction of future illness, diagnostic clarity and a level of disease
      description that would guide treatment choice. However, the choice of sample and
      form of analysis used to produce useful biomarkers is still uncertain. In this
      review, advances from recent studies spanning the technical spectrum are
      presented together with comment on their comparative strengths and weaknesses. To
      date, these studies have aided our understanding of the pathological processes
      associated with illness much more than they have provided robust biomarkers. A
      number of reasons for this observation are suggested, as are new strategies for
      the extraction of biomarkers from large '-omics' datasets. 

PMID- 25601398
TI  - Oxygen desaturation and adverse events during 6-min walk testing in patients with
      COPD.
AB  - BACKGROUND AND OBJECTIVE: The 6-min walk test (6MWT) is a simple test assessing
      functional capacity, but concerns about risks of substantial oxygen desaturation
      in pulmonary patients have led to non-adherence to the standardised American
      Thoracic Society guideline. We evaluated the safety of the 6MWT in stable COPD
      patients and compared the incidence of adverse events in patients with and
      without substantial exertional hypoxaemia. METHODS: 6MWT data were obtained for
      1136 patients with moderate to very severe COPD. Demographics, adverse events,
      oxygen saturation (SpO2), 6-min walk distance, lung function and quality of life
      measures were compared between patients with substantial exertional hypoxaemia
      (nadir SpO2 < 85%) and those without (SpO2 >= 85%). Comparisons were made using
      Mann-Whitney U-test for continuous variables and Fisher's exact test for
      categorical variables. RESULTS: Twenty-five patients (2.2%) had adverse events,
      the most common being dizziness, chest tightness, chest pain and palpitations.
      Substantial exertional hypoxaemia did not increase the incidence of adverse
      events. No significant morbidity or mortality was recorded. Patients with adverse
      events had lower baseline SpO2, worse quality of life scores, and higher
      depression and anxiety scores. However, no significant differences were seen in
      anthropometric data, spirometric values or SpO2 during and after the 6MWT.
      CONCLUSIONS: Asymptomatic exertional hypoxaemia is not associated with an
      increased incidence of adverse events during 6MWT in COPD patients. Our data
      support the ATS guideline that the 6MWT should be continued in the absence of
      symptoms and that intermittent oximetry monitoring does not assist in preventing
      adverse events.

PMID- 25601399
TI  - Cole Haynes: on the trail of mitochondrial dysfunction.

PMID- 25601400
TI  - Moving beyond molecular mechanisms.
AB  - A major goal in cell biology is to bridge the gap in our understanding of how
      molecular mechanisms contribute to cell and organismal physiology. Approaches
      well established in the physical sciences could be instrumental in achieving this
      goal. A better integration of the physical sciences with cell biology will
      therefore be an important step in our quest to decipher how cells work together
      to construct a living organism. 

PMID- 25601402
TI  - The Nck-interacting kinase NIK increases Arp2/3 complex activity by
      phosphorylating the Arp2 subunit.
AB  - The nucleating activity of the Arp2/3 complex promotes the assembly of branched
      actin filaments that drive plasma membrane protrusion in migrating cells. Arp2/3
      complex binding to nucleation-promoting factors of the WASP and WAVE families was
      previously thought to be sufficient to increase nucleating activity. However,
      phosphorylation of the Arp2 subunit was recently shown to be necessary for Arp2/3
      complex activity. We show in mammary carcinoma cells that mutant Arp2 lacking
      phosphorylation assembled with endogenous subunits and dominantly suppressed
      actin filament assembly and membrane protrusion. We also report that Nck
      interacting kinase (NIK), a MAP4K4, binds and directly phosphorylates the Arp2
      subunit, which increases the nucleating activity of the Arp2/3 complex. In cells,
      NIK kinase activity was necessary for increased Arp2 phosphorylation and plasma
      membrane protrusion in response to epidermal growth factor. NIK is the first
      kinase shown to phosphorylate and increase the activity of the Arp2/3 complex,
      and our findings suggest that it integrates growth factor regulation of actin
      filament dynamics. 

PMID- 25601403
TI  - Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions.
AB  - Antigen processing and presentation and cytotoxic targeting depend on the
      activities of several lysosomal enzymes that require mannose 6-phosphate (M6P)
      sorting signals for efficient intracellular transport and localization. In this
      paper, we show that mice deficient in the formation of M6P residues exhibit
      significant loss of cathepsin proteases in B cells, leading to lysosomal
      dysfunction with accumulation of storage material, impaired antigen processing
      and presentation, and subsequent defects in B cell maturation and antibody
      production. The targeting of lysosomal and granular enzymes lacking M6P residues
      is less affected in dendritic cells and T cells and sufficient for maintenance of
      degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin
      levels and antibody responses to vaccination in patients. Our data demonstrate
      the critical role of M6P-dependent transport routes for B cell functions in vivo
      and humoral immunity in mice and human. 

PMID- 25601401
TI  - Peaks cloaked in the mist: the landscape of mammalian replication origins.
AB  - Replication of mammalian genomes starts at sites termed replication origins,
      which historically have been difficult to locate as a result of large genome
      sizes, limited power of genetic identification schemes, and rareness and
      fragility of initiation intermediates. However, origins are now mapped by the
      thousands using microarrays and sequencing techniques. Independent studies show
      modest concordance, suggesting that mammalian origins can form at any DNA
      sequence but are suppressed by read-through transcription or that they can
      overlap the 5' end or even the entire gene. These results require a critical
      reevaluation of whether origins form at specific DNA elements and/or epigenetic
      signals or require no such determinants. 

PMID- 25601404
TI  - Multiple assembly mechanisms anchor the KMN spindle checkpoint platform at human
      mitotic kinetochores.
AB  - During mitosis, the spindle checkpoint senses kinetochores not properly attached
      to spindle microtubules and prevents precocious sister-chromatid separation and
      aneuploidy. The constitutive centromere-associated network (CCAN) at inner
      kinetochores anchors the KMN network consisting of Knl1, the Mis12 complex
      (Mis12C), and the Ndc80 complex (Ndc80C) at outer kinetochores. KMN is a critical
      kinetochore receptor for both microtubules and checkpoint proteins. Here, we show
      that nearly complete inactivation of KMN in human cells through multiple
      strategies produced strong checkpoint defects even when all kinetochores lacked
      microtubule attachment. These KMN-inactivating strategies reveal multiple KMN
      assembly mechanisms at human mitotic kinetochores. In one mechanism, the
      centromeric kinase Aurora B phosphorylates Mis12C and strengthens its binding to
      the CCAN subunit CENP-C. In another, CENP-T contributes to KMN attachment in a
      CENP-H-I-K-dependent manner. Our study provides insights into the mechanisms of
      mitosis-specific assembly of the checkpoint platform KMN at human kinetochores. 

PMID- 25601406
TI  - Biventricular pacing for bradycardia: are we there yet?

PMID- 25601405
TI  - A DPP-mediated feed-forward loop canalizes morphogenesis during Drosophila dorsal
      closure.
AB  - Development is robust because nature has selected various mechanisms to buffer
      the deleterious effects of environmental and genetic variations to deliver
      phenotypic stability. Robustness relies on smart network motifs such as feed
      forward loops (FFLs) that ensure the reliable interpretation of developmental
      signals. In this paper, we show that Decapentaplegic (DPP) and JNK form a
      coherent FFL that controls the specification and differentiation of leading edge
      cells during Drosophila melanogaster dorsal closure (DC). We provide molecular
      evidence that through repression by Brinker (Brk), the DPP branch of the FFL
      filters unwanted JNK activity. High-throughput live imaging revealed that this
      DPP/Brk branch is dispensable for DC under normal conditions but is required when
      embryos are subjected to thermal stress. Our results indicate that the wiring of
      DPP signaling buffers against environmental challenges and canalizes cell
      identity. We propose that the main function of DPP pathway during Drosophila DC
      is to ensure robust morphogenesis, a distinct function from its well-established
      ability to spread spatial information. 

PMID- 25601407
TI  - Smartphone ECG for evaluation of STEMI: results of the ST LEUIS Pilot Study.
AB  - BACKGROUND: 12-lead ECG is a critical component of initial evaluation of cardiac
      ischemia, but has traditionally been limited to large, dedicated equipment in
      medical care environments. Smartphones provide a potential alternative platform
      for the extension of ECG to new care settings and to improve timeliness of care.
      OBJECTIVE: To gain experience with smartphone electrocardiography prior to
      designing a larger multicenter study evaluating standard 12-lead ECG compared to
      smartphone ECG. METHODS: 6 patients for whom the hospital STEMI protocol was
      activated were evaluated with traditional 12-lead ECG followed immediately by a
      smartphone ECG using right (VnR) and left (VnL) limb leads for precordial
      grounding. The AliveCorTM Heart Monitor was utilized for this study. All tracings
      were taken prior to catheterization or immediately after revascularization while
      still in the catheterization laboratory. RESULTS: The smartphone ECG had
      excellent correlation with the gold standard 12-lead ECG in all patients. Four
      out of six tracings were judged to meet STEMI criteria on both modalities as
      determined by three experienced cardiologists, and in the remaining two,
      consensus indicated a non-STEMI ECG diagnosis. No significant difference was
      noted between VnR and VnL. CONCLUSIONS: Smartphone based electrocardiography is a
      promising, developing technology intended to increase availability and speed of
      electrocardiographic evaluation. This study confirmed the potential of a
      smartphone ECG for evaluation of acute ischemia and the feasibility of studying
      this technology further to define the diagnostic accuracy, limitations and
      appropriate use of this new technology.

PMID- 25601408
TI  - Early resolution of ST-segment elevation after reperfusion therapy for acute
      myocardial infarction: Its relation to echocardiography-determined left
      ventricular global and regional function and deformation.
AB  - AIMS: To evaluate the relationships between ST-segment resolution (STR) and
      echocardiography-determined left ventricular (LV) global and regional function
      and deformation in the sub-acute phase of STEMI. METHODS AND RESULTS: STR,
      defined as either complete (>=70%) or incomplete (<70%), was evaluated 60minutes
      after primary percutaneous coronary intervention (PCI) of 84 STEMI patients.
      Conventional two-dimensional (2D) echocardiography and 2D speckle-tracking
      echocardiography (STE) were performed at 3-7days after reperfusion. LV
      deformation [including the infarction-related regional longitudinal (RLS),
      circumferential (RCS), and radial (RRS) strains, and global longitudinal (GLS),
      circumferential (GCS), and radial (GRS) strains] was measured by 2D STE. LV
      segmental function was assessed by wall motion score index (WMSI). Patients in
      incomplete vs. complete STR groups had higher WMSI (p<0.001); decreased peak
      amplitude of RLS (p<0.001), RCS (p=0.008), RRS (p=0.002); and decreased peak
      amplitude of GLS (p<0.001), GCS (p<0.001), GRS (p=0.003). RLS (r=0.27, p=0.015)
      and GLS (r=0.33, p=0.003) were best correlates of STR at the regional and global
      level, respectively. CONCLUSIONS: STR correlated with global and regional LV
      function and deformation in patients with sub-acute phase of STEMI after PCI. RLS
      and GLS were the strongest correlates of STR at the regional and global levels,
      respectively.

PMID- 25601410
TI  - Electrocardiogram score for the selection of reperfusion strategy in early
      latecomers with ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: The clinical benefit of percutaneous coronary intervention (PCI) is
      controversial in ST-segment elevation myocardial infarction (STEMI) patients
      presenting 12-72 hours after symptom onset. Several studies suggested this
      conflicting result was associated with myocardial area at risk (MaR) of enrolled
      patients. MaR could be estimated by the electrocardiogram (ECG) score. Our
      objective was to evaluate the benefits of PCI in STEMI latecomers with different
      MaR. METHODS: We constructed a prospective cohort involving 436 patients
      presenting 12-72 hours after STEMI onset and who met an inclusion criteria. 218
      underwent PCI and 218 received the optimal medical therapy (OMT) alone.
      Individual MaR was quantified by the combined Aldrich ST and Selvester QRS score.
      The primary endpoint was a composite of cardiovascular death, reinfarction or
      revascularization within two years. RESULTS: The 2-year cumulative primary
      endpoint rate was respectively 9.2% in PCI group and 5.3% in OMT group when
      MaR<35% (adjusted hazard ratio for PCI vs. OMT, 1.855; 95% confidence interval
      [CI], 0.617-5.575; P=0.271), and was 12.8% in PCI group and 23.1% in OMT group
      when MaR >=35% (adjusted hazard ratio for PCI vs. OMT, 0.448; 95% CI, 0.228
      0.884; P=0.021). CONCLUSION: The benefit of PCI for the STEMI latecomers was
      associated with the MaR. PCI, compared with OMT, could significantly reduce the 2
      year primary outcomes in patients with MaR>=35%, but not in ones with MaR<35%.

PMID- 25601409
TI  - Reproducibility of QTc interval changes after meal intake.
AB  - BACKGROUND: Detection of QTc decreases after meal intake was proposed as a
      possible proof of assay sensitivity in studies of drug-induced QTc changes.
      However, day-to-day reproducibility of QTc decreases after meal intake has not
      been established. METHODS: Holter recordings were available from 4 different
      baseline drug-free days of a thorough QT study in 157 females and 164 males.
      During each of the baselines, subjects were fasting in the morning and were
      served standardized lunch. Heart rates and QTc intervals were measured during
      repeated time-points throughout each study day. Two investigations were
      performed. In the first investigation, 3 heart rate and QTc measurements 1, 2,
      and 3h after lunch were averaged in each subject and corrected for the morning
      fasting baseline. Reproducibility of heart rate and QTc changes after the meal on
      different days X and Y was assessed by normalized repeatability coefficients
      2*|MX-MY|/|MX+MY|, where MX and MY are measurements in the same subject on days X
      and Y, respectively. These were compared for heart rate and QTc changes after
      meal for different pairs of baseline days. In the second investigation, 36
      females and 41 males were considered who received moxifloxacin during the source
      thorough QT study. The QTc increases after moxifloxacin were expressed by
      averaging 3 time-point values and corrected for placebo QTc values measured
      25days apart. In the same subjects, QTc readings after lunch were also corrected
      for fasting baseline readings 25days apart. QTc responses to moxifloxacin and to
      meal intake were compared. RESULTS: Repeatability of QTc decreases after meal was
      significantly (p<0.0000001) poorer than that of heart rate increases after meal.
      Of the subjects receiving moxifloxacin during the study, 6% did not show QTc
      prolongation on moxifloxacin while 39% have not shown QTc shortening after lunch
      (p<0.00001). CONCLUSION: The reproducibility of QTc changes after meal is
      limited. The power of proving QTc assay sensitivity by the detection of QTc
      changes after meal is poorer than the power of the standard moxifloxacin-based
      assay sensitivity.

PMID- 25601411
TI  - Pharmaceutical and biomedical applications of surface engineered carbon
      nanotubes.
AB  - Surface engineered carbon nanotubes (CNTs) are attracting recent attention of
      scientists owing to their vivid biomedical and pharmaceutical applications. The
      focus of this review is to highlight the important role of surface engineered
      CNTs in the highly challenging but rewarding area of nanotechnology. The major
      strength of this review lies in highlighting the exciting applications of CNTs to
      boost the research efforts, which unfortunately are otherwise scattered in the
      literature making the reading non-coherent and non-homogeneous. 

PMID- 25601412
TI  - Fructose 1,6-bisphosphatase deficiency: clinical, biochemical and genetic
      features in French patients.
AB  - Fructose-1,6-bisphosphatase (FBPase) deficiency is a very rare autosomal
      recessive disorder caused by a mutation of the fructose-1,6-bisphosphatase
      gene(FBP1). Disease is mainly revealed by hypoglycemia and lactic acidosis, both
      symptoms being characteristic for an enzymatic block in the last steps of the
      gluconeogenesis. Twelve patients with FBPase deficiency were diagnosed in France
      in the 2001-2013 period, using a diagnostic system based on a single blood sample
      which allows simultaneous enzyme activity measurement on mononuclear white blood
      cells and molecular analysis. Sequencing of exons and intron-exon junctions of
      FBP1 gene was completed in unsolved cases by a gene dosage assay developed for
      each exon. For most patients, first metabolic decompensation occurred before two
      years of age with a similar sequence: the triggering factors were fever, fasting,
      or decrease of food intake. However, diagnosis was made late at a mean age of 3
      years, as mitochondrial defects or glycogen storage diseases were firstly
      suspected. Enzyme activity in leukocytes was dramatically decreased (<10%).
      Twelve different mutations were identified in 22 alleles among them seven were
      novels: one missense mutation c.472C > T, one point deletion c.48del, one point
      duplication c.865dupA, one deletion-insertion, and two splice mutations (c.427
      1del and c.825 + 1G > A). We described the first intragenic deletion in FBP1
      (g.97,364,754_97,382,011del) in homozygous state. Our report also confirms that
      this very rare disease is misdiagnosed, as other energetic defects are firstly
      suspected.

PMID- 25601415
TI  - [Ln(III)-Mn(II)-Ln(III)] heterometallic compounds: rare linear SMMs with divalent
      manganese ions.
AB  - The reaction of Mn(OAc)2.4H2O and Ln(NO3)3.6H2O with N-(2-aminopropyl)-2
      hydroxybenzamide and salicylic aldehyde in methanol/methylene dichloride produces
      yellow crystals of Ln2Mn(C7H5O2)8 (Ln = Gd (), Tb (), Dy (), Ho () and Er ()), in
      the presence of triethylamine. Three metal ions are connected by six MU2
      phenolate oxygen atoms of six salicylic aldehyde ligands, resulting in perfect
      linear [Ln(III)-Mn(II)-Ln(III)] structures. Magnetic studies of these complexes
      have been performed and AC susceptibility measurements show the presence of a
      temperature-dependent out-of-phase ac signal for complexes and indicating single
      molecule magnet (SMM) behavior. The Dy(III)2Mn(II) compound shows double
      relaxation pathways which may originate from the single ion behavior of
      individual Dy(III) ions and the weak coupling between Dy(III) and Mn(II) ions,
      respectively. The Ueff of 92.4(2) K is a relatively high value among 3d-4f SMMs.
      Moreover, complexes and represent the first linear Mn-Ln SMMs containing only
      divalent manganese ions as far as we know. The result suggests the positive
      effects of magnetic coupling to enhance their SMM behavior, presenting a
      promising strategy for constructing efficient heterometallic SMMs. 

PMID- 25601413
TI  - Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate
      dehydrogenase complex activity by combination with dichloroacetate.
AB  - Pyruvate dehydrogenase complex (PDHC) is a key enzyme in metabolism linking
      glycolysis to tricarboxylic acid cycle and its activity is tightly regulated by
      phosphorylation catalyzed by four pyruvate dehydrogenase kinase (PDK) isoforms.
      PDKs are pharmacological targets for several human diseases including cancer,
      diabetes, obesity, heart failure, and inherited PDHC deficiency. We investigated
      the inhibitory activity of phenylbutyrate toward PDKs and found that PDK isoforms
      1-to-3 are inhibited whereas PDK4 is unaffected. Moreover, docking studies
      revealed putative binding sites of phenylbutyrate on PDK2 and 3 that are located
      on different sites compared to dichloroacetate (DCA), a previously known PDK
      inhibitor. Based on these findings, we showed both in cells and in mice that
      phenylbutyrate combined to DCA results in greater increase of PDHC activity
      compared to each drug alone. These results suggest that therapeutic efficacy can
      be enhanced by combination of drugs increasing PDHC enzyme activity. 

PMID- 25601414
TI  - Controlling fertilization and cAMP signaling in sperm by optogenetics.
AB  - Optogenetics is a powerful technique to control cellular activity by light. The
      light-gated Channelrhodopsin has been widely used to study and manipulate
      neuronal activity in vivo, whereas optogenetic control of second messengers in
      vivo has not been examined in depth. In this study, we present a transgenic mouse
      model expressing a photoactivated adenylyl cyclase (bPAC) in sperm. In transgenic
      sperm, bPAC mimics the action of the endogenous soluble adenylyl cyclase (SACY)
      that is required for motility and fertilization: light-stimulation rapidly
      elevates cAMP, accelerates the flagellar beat, and, thereby, changes swimming
      behavior of sperm. Furthermore, bPAC replaces endogenous adenylyl cyclase
      activity. In mutant sperm lacking the bicarbonate-stimulated SACY activity, bPAC
      restored motility after light-stimulation and, thereby, enabled sperm to
      fertilize oocytes in vitro. We show that optogenetic control of cAMP in vivo
      allows to non-invasively study cAMP signaling, to control behaviors of single
      cells, and to restore a fundamental biological process such as fertilization. 

PMID- 25601416
TI  - Combined exposure to bacteria and cigarette smoke resembles characteristic
      phenotypes of human COPD in a murine disease model.
AB  - Abundant microbial colonization is a hallmark of COPD and smoke exposure likely
      increases the susceptibility to colonization and infection. The aim of the
      present study was to characterize the pulmonary changes of a combined exposure to
      cigarette smoke (CS) and microbial challenge in a preclinical murine COPD model.
      Animals were exposed to CS for 2 weeks, 3, and 6 months. Low and high doses of
      heat inactivated nontypeable Haemophilus influenzae (NTHi) were administered by
      inhalation during the whole exposure time. Pulmonary changes were analyzed by
      stereology, pulmonary function tests, measurements of inflammatory cells and
      mediators, and histopathology. Exposure of smoke in a relatively low
      concentration caused COPD-like changes of pulmonary function and only little
      inflammation. The coadministration of low dose NTHi (ld-NTHi) augmented a
      macrophage dominated inflammatory profile, while high dose NTHi (hd-NTHi) induced
      a neutrophilic inflammatory pattern. IL-17A secretion was solely dependent on the
      exposure to NTHi. Also goblet cell metaplasia and the formation of lymphoid
      aggregates depended on exposure to bacteria. In conclusion, the combination of
      exposure to smoke and bacterial compounds resulted in a mouse model that
      resembles several aspects of human disease. Exposure to microbial structural
      components appears necessary to model important pathologic features of the
      disease and the quantity of the exposure with microorganisms has a strong effect
      on the phenotype. 

PMID- 25601417
TI  - A novel homozygous mutation in the SLCO2A1 gene is associated with severe primary
      hypertrophic osteoarthropathy phenotype in a Saudi patient.

PMID- 25601418
TI  - A summary of the Proceedings of the Twelfth International Symposium on the
      Neurobiology and Neuroendocrinology of Aging, Bregenz, Austria July 27-August 1,
      2014.
AB  - A summary of the Twelfth International Symposium on the Neurobiology and
      Neuroendocrinology of Aging that was held July 27-August 1, 2014 in Bregenz,
      Austria, is presented. Fifteen of the speakers that presented at the conference
      submitted review papers covering the topic of their presentation as well as an
      overview of their respective fields and are included in this special issue. The
      abstracts from each poster presentation as well as seven of the speakers'
      abstracts are also included at the end of the preface to the special issue. 

PMID- 25601419
TI  - A validation of an intelligent decision-making support system for the nutrition
      diagnosis of bariatric surgery patients.
AB  - BACKGROUND: Bariatric surgery is an important method for treatment of morbid
      obesity. It is known that significant nutritional deficiencies might occur after
      surgery, such as, calorie-protein malnutrition, iron deficiency anemia, and lack
      of vitamin B12, thiamine, and folic acid. OBJECTIVE: The objective of our study
      was to validate a computerized intelligent decision support system that suggests
      nutritional diagnoses of patients submitted to bariatric surgery. METHODS: There
      were fifteen clinical cases that were developed and sent to three dietitians in
      order to evaluate and define a nutritional diagnosis. After this step, the cases
      were sent to four bariatric surgery expert dietitians who were aiming to
      collaborate on a gold standard. The nutritional diagnosis was to be defined
      individually, and any disagreements were solved through a consensus. The final
      result was used as the gold standard. Bayesian networks were used to implement
      the system, and database training was done with Shell Netica. For the system
      validation, a similar answer rate was calculated, as well as the specificity and
      sensibility. Receiver operating characteristic (ROC) curves were projected to
      each nutritional diagnosis. RESULTS: Among the four experts, the rate of similar
      answers found was 80% (48/60) to 93% (56/60), depending on the nutritional
      diagnosis. The rate of similar answers of the system, compared to the gold
      standard, was 100% (60/60). The system sensibility and specificity were 95.0%.
      The ROC curves projection showed that the system was able to represent the expert
      knowledge (gold standard), and to help them in their daily tasks. CONCLUSIONS:
      The system that was developed was validated to be used by health care
      professionals for decision-making support in their nutritional diagnosis of
      patients submitted to bariatric surgery.

PMID- 25601420
TI  - Unraveling oxidative stress. From yeast to human therapy.

PMID- 25601422
TI  - Oral erythromycin therapy in epidermolysis bullosa simplex generalized severe.

PMID- 25601421
TI  - Increase of Framingham cardiovascular disease risk score is associated with
      severity of lower urinary tract symptoms.
AB  - OBJECTIVE: To determine the relationship between lower urinary tract symptoms
      (LUTS)/benign prostatic hyperplasia (BPH) and 10-year risk of cardiovascular
      disease (CVD) assessed by the Framingham CVD risk score in a cohort of patients
      without previous episodes of stroke and/or acute myocardial infarction. PATIENTS
      AND METHODS: From September 2010 to September 2014, 336 consecutive patients with
      BPH-related LUTS were prospectively enrolled. The general 10-year Framingham CVD
      risk score, expressed as percentage and assessing the risk of atherosclerotic CVD
      events, was calculated for each patient. Individuals with low risk had <=10% CVD
      risk at 10 years, with intermediate risk 10-20% and with high risk >=20%.
      Logistic regression analyses were used to identify variables for predicting a
      Framingham CVD risk score of >=10% and moderate-severe LUTS (International
      Prostate Symptom Score [IPSS] >=8), adjusted for confounding factors. RESULTS: As
      category of Framingham CVD risk score increased, we observed higher IPSS (18.0 vs
      18.50 vs 19.0; P < 0.05), high IPSS-voiding (6.0 vs 9.0 vs 9.5; P < 0.05) and
      worse sexual function. Prostate volume significantly increased in those with
      intermediate- vs low-risk scores (54.5 vs 44.1 mL; P < 0.05). Multivariate
      logistic regression analysis showed that intermediate- [odds ratio (OR) 8.65; P <
      0.01) and high-risk scores (OR 1.79; P < 0.05) were independently associated with
      moderate-severe LUTS. At age-adjusted logistic regression analysis, moderate
      severe LUTS was independently associated with Framingham CVD risk score of >=10%
      (OR 5.91; P < 0.05). CONCLUSION: Our cross-sectional study in a cohort of
      patients with LUTS-BPH showed an increase of more than five-fold of having a
      Framingham CVD risk score of >=10% in men with moderate-severe LUTS.

PMID- 25601423
TI  - Entropic self-assembly of freely rotating polyhedral particles confined to a flat
      interface.
AB  - The self-assembly of hard polyhedral particles confined to a flat interface is
      studied using Monte Carlo simulations. The particles are pinned to the interface
      by restricting their movement in the direction perpendicular to it while allowing
      their free rotations. The six different polyhedral shapes studied in this work
      are selected from a family of truncated cubes defined by a truncation parameter,
      s, which varies from cubes (s = 0) via cuboctahedra (s = 0.5) to octahedra (s =
      1). Our results suggest that shapes with small values of s show square-like
      behavior whereas shapes with large values of s tend to show more disc-like
      behavior. At an intermediate value of s = 0.4, the phase behavior of the system
      shows both square-like and disc-like features. The results are also compared with
      the phase behavior of 3D bulk polyhedra and of 2D rounded hard squares. Both
      comparisons reveal key similarities in the number and sequence of mesophases and
      solid phases observed. These insights on 2D entropic self-assembly of polyhedral
      particles is a first step toward understanding the self-assembly of particles at
      fluid-fluid interfaces, which is driven by a complex interplay of entropic and
      enthalpic forces. A first-order analysis of the particle-surface energies
      associated with a fluid-fluid interface indicates that such enthalpic
      interactions will be particularly important in determining particle orientation
      behavior at low to intermediate concentrations. 

PMID- 25601424
TI  - Safe identification of the ERI state in St. Jude Medical Identity(r) family
      pacemakers.

PMID- 25601425
TI  - Assessing treatment-as-usual provided to control groups in adherence trials:
      Exploring the use of an open-ended questionnaire for identifying behaviour change
      techniques.
AB  - OBJECTIVE: Reporting guidelines call for descriptions of control group support in
      equal detail as for interventions. However, how to assess the active content
      (behaviour change techniques (BCTs)) of treatment-as-usual (TAU) delivered to
      control groups in trials remains unclear. The objective of this study is to pre
      test a method of assessing TAU in a multicentre cost-effectiveness trial of an
      HIV-treatment adherence intervention. DESIGN: HIV-nurses (N = 21) completed a
      semi-structured open-ended questionnaire enquiring about TAU adherence
      counselling. Two coders independently coded BCTs. MAIN OUTCOME MEASURES:
      Completeness and clarity of nurse responses, inter-coder reliabilities and the
      type of BCTs reported were examined. RESULTS: The clarity and completeness of
      nurse responses were adequate. Twenty-three of the 26 identified BCTs could be
      reliably coded (mean kappa = .79; mean agreement rate = 96%) and three BCTs
      scored below kappa = .60. Total number of BCTs reported per nurse ranged between
      7 and 19 (M = 13.86, SD = 3.35). CONCLUSIONS: This study suggests that the TAU
      open-ended questionnaire is a feasible and reliable tool to capture active
      content of support provided to control participants in a multicentre adherence
      intervention trial. Considerable variability in the number of BCTs provided to
      control patients was observed, illustrating the importance of reliably collecting
      and accurately reporting control group support.

PMID- 25601426
TI  - Re: 'Assessment of long-term donor-site morbidity after harvesting the latissimus
      dorsi flap for neonatal myelomeningocele repair'.

PMID- 25601427
TI  - Human genetics of HDL: Insight into particle metabolism and function.
AB  - Levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to
      cardiovascular disease risk and HDL particles possess a variety of anti
      atherosclerotic properties. However, several recent clinical trials aimed at
      raising HDL-C levels have failed to yield the expected improvement in clinical
      outcomes, highlighting the need for a better understanding of HDL particle
      function and metabolism. Human genetic studies have proven to be an outstanding
      source of insight regarding the biology of this complex lipoprotein class. In
      particular, the study of rare genetic disorders of HDL has identified a number of
      key players in HDL metabolism, some of which represent current or future
      therapeutic targets. More recently, genetic association studies have identified a
      large number of additional genes and proteins involved in HDL metabolism. The
      purpose of this review is to summarize progress in the study of HDL genetics and
      how these insights have contributed to our understanding of the metabolic
      pathways and function of HDL leading to opportunities for the long-elusive HDL
      based therapies. 

PMID- 25601428
TI  - Nurses' perceived benefits of trauma nursing rounds (TNR) on clinical practice in
      an Australian emergency department: a mixed methods study.
AB  - BACKGROUND: Trauma nursing rounds (TNR) are a unique type of bedside teaching
      round that facilitate discussion of individual trauma patient's condition and
      care, and provide a novel and innovative approach to nursing education in an
      informal setting. This study introduced TNR to the emergency department in an
      Australian metropolitan hospital. METHODS: Registered nurses, assistants-in
      nursing, and nursing students participated in seven TNR over a 12-week period.
      The primary care nurse presented the trauma case utilising a modified handover
      tool. This was followed by discussion of the patient's condition and management
      among all those present including the patient. A participant questionnaire
      provided feedback from the nurses about TNR perceived benefits. A representative
      sample of participants was subsequently interviewed. RESULTS: Fifty-three
      participants attended the rounds, 47 responded to the questionnaire, and nine
      were interviewed. Participants were universally positive about the TNR structure
      and its potential impact on clinical practice. Interviewees indicated that TNR
      have the potential to enhance collegiality, and allow the patients and their
      families to be involved and informed in their care. CONCLUSIONS: The introduction
      of TNR was successful. TNR provide the potential to improve assessment and care
      of trauma patients, promote collaborative learning, and promote patients'
      understanding and involvement in their care.

PMID- 25601429
TI  - Is the Modified Early Warning Score able to enhance clinical observation to
      detect deteriorating patients earlier in an Accident & Emergency Department?
AB  - BACKGROUND: Currently there is no study to prove the accuracy of any early
      warning system on a group of patients who are waiting for in-patient beds in
      emergency department (ED). The study objective is to compare the performances of
      detecting patient deterioration with and without using the Modified Early Warning
      Score for a group of patients who are waiting for in-patient beds in a public ED.
      METHODS: An observational study was conducted in a public ED in Hong Kong between
      January and March 2013. During this period, the Modified Early Warning Score
      (MEWS) was incorporated into current nursing practice for patient monitoring in
      selected days. Nurses then made decision according to the MEWS to notify senior
      nurses or senior doctors of patient deterioration. There was a comparison group
      with target patients being monitored without using the MEWS. RESULTS: A total of
      545 patients were recruited, with 269 patients in the MEWS group. Using the MEWS
      for patient observation had a 100% sensitivity and a 98.3% specificity in
      detecting patient deterioration, while there was also a high sensitivity and a
      high specificity (100% and 97.8%) in the comparison group. The findings also
      showed that respiratory rate was a significant vital sign to detect patient
      deterioration. CONCLUSIONS: Using the MEWS for patient monitoring did not
      significantly enhance the performance in detecting patient deterioration for a
      group of patients who are waiting for in-patient beds in a public ED. However,
      the MEWS may be beneficial to less experienced nurses who have less clinical
      experience to identify patient deterioration.

PMID- 25601430
TI  - Flow reduction of a neonatal stented arterial duct by covered coronary stent.
AB  - The final flow rate through a stented duct is variable and depends on stent
      diameter, ductal length, and ductal tissue protrusion after ductal constriction.
      Typically after duct stenting, there is initially mild overperfusion which may
      require some antifailure treatment. Severe heart failure is uncommon, but in some
      cases flow reduction is required. We present a case of overperfusion after
      arterial duct stent implantation which was successfully managed with implantation
      of covered stents.

PMID- 25601431
TI  - Lysosomes and unfolded protein response, determinants of differential resistance
      of melanoma cells to vinca alkaloids.
AB  - On account of its strong ability to become chemoresistant after a primary
      response to drugs, malignant melanoma (MM) remains a therapeutic challenge. This
      study focuses on acquired resistance to vinca alkaloids (VAs) using VA-resistant
      MM cell lines (CAL1R-VCR, CAL1R-VDS, and CAL1R-VRB), established by long-term
      continuous exposure of parental CAL1-wt cells to vincristine (VCR), vindesine
      (VDS), or vinorelbine (VRB), respectively. Transcriptomic profiling using rma and
      rdam methods led to distinguish two cell groups: CAL1R-VCR and CAL1R-VDS, CAL1R
      VRB, and CAL1-wt. mgsa of the specifically altered genes in the first group
      evidenced the GO terms 'lysosomal lumen' and 'vacuolar lumen' linked to
      underexpressed genes, and 'endoplasmic reticulum (ER) stress response' associated
      with overexpressed genes. A specific reduction of lysosomal enzymes, independent
      of acidic vacuole organelle (AVO) turnover, was observed (LTG probe) in CAL1R-VCR
      and CAL1R-VDS cells. It was associated with the specific lowering of cathepsin B
      and L, known to be involved in the lysosomal pathway of apoptosis. Confirming
      gene profiling, the same groups (CAL1R-VCR and CAL1R-VDS, CAL1-wt and CAL1R-VRB)
      could be distinguished regarding the VA-mediated changes on mean size areas and
      on acidic compartment volumes. These two parameters were reduced in CAL1R-VCR and
      CAL1R-VDS cells, suggesting a smaller AVO accumulation and thus a reduced
      sensitivity to lysosomal membrane permeabilization-mediated apoptosis. In
      addition, 'ER stress response' inhibition by tauroursodeoxycholic acid induced a
      higher VA sensitization of the first cell group. In conclusion, lysosomes and
      unfolded protein response could be key determinants of the differential
      resistance of MM to VAs. 

PMID- 25601432
TI  - Knitting up 2,7-disubstituted carbazole based oligomers through supramolecular
      interactions for their application in organic thin film transistors.
AB  - For the design and development of organic electronic devices, the main focus is
      particularly on the synthesis of new organic semiconductors and dielectric
      materials. Molecular engineering is another effective strategy, in this direction
      which has been explored successfully in this study through synthesis of a pi
      conjugated oligomer CbzTPAU2, with Mw = 2169. This bow shaped oligomer has its
      core unit made of 2,7-disubstituted carbazole which further has been connected to
      its end-terminal unit TPAU2 by 1,4-bis(decyloxy)-2,5-diethynylbenzene. The
      presence of a uracil moiety on end terminals of CbzTPAU2 has triggered the self
      assembly of CbzTPAU2 molecules through knitting up of each of these single units
      through four Uracil-Uracil intermolecular hydrogen bonds (UU) per CbzTPAU2 unit.
      An Atomic Force Microscope (AFM) study was employed to explore the directionality
      of hydrogen bonding. Further, the effect of solvent polarity on the stability of
      UU bonding in CbzTPAU2 oligomers has also been reported here in this study. The
      potential of these self-assembled CbzTPAU2 oligomers when explored as charge
      transporting layers in OTFTs has shown p-type behaviour. The OTFT device bottom
      gate, top-contact when fabricated on the heavily doped n-type Si wafer with SiO2
      as a gate dielectric (200 nm) has shown a good on/off ratio 3.43 * 10(3) and with
      an average hole mobility of 0.167 cm(2) V(-1) s(-1). 

PMID- 25601433
TI  - Genetic modifiers of secondary iron overload in beta thalassemia major.

PMID- 25601434
TI  - Compound IMM-H004, a novel coumarin derivative, protects against CA1 cell loss
      and spatial learning impairments resulting from transient global ischemia.
AB  - AIMS: Compound IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]
      2H-chromen-2-one) is a new synthetic derivative of coumarin, and previous studies
      showed that it exhibited antioxidant and neuroprotective roles in focal cerebral
      ischemia. However, we know little about the compound's function in transient
      global ischemia. This study is to investigate whether compound IMM-H004 can
      protect against transient global ischemic injury. METHODS: Four-vessel occlusion
      (4VO) rat model was induced for a 20-min occlusion and different times of
      reperfusion to mimic transient global cerebral ischemia. IMM-H004 (3, 6, 9 mg/kg)
      or Edaravone (6 mg/kg) was administered after 30 min of reperfusion. Morris water
      maze tests were used to estimate the ability of spatial learning and memory.
      Nissl staining, TUNEL assay and Immunoblot for Bax/Bcl-2 and activated caspase-3
      were used to detect hippocampal neuron injury. Immunoblot for PSD-95 and synapsin
      1, and electron microscopy were used to observe synaptic function. RESULTS:
      Compared with vehicle group, IMM-H004 significantly improved the spatial learning
      performance and exhibited less CA1 neurons loss. The expressions of Bax/Bcl-2 and
      activated caspase-3 were decreased. IMM-H004 also ameliorated synaptic structure,
      decreased PSD-95 and increased synapsin 1 expression. CONCLUSION: These findings
      suggested that IMM-H004 exerted neuroprotective role in global ischemia by
      reducing apoptosis and maintaining the integrity of synaptic structure.

PMID- 25601435
TI  - Some Problems with Randomized Controlled Trials and Some Viable Alternatives.
AB  - Randomized controlled trials (RCTs) are currently the dominant methodology for
      evaluating psychological treatments. They are widely regarded as the gold
      standard, and in the current climate, it is unlikely that any particular
      psychotherapy would be considered evidence-based unless it had been subjected to
      at least one, and usually more, RCTs. Despite the esteem within which they are
      held, RCTs have serious shortcomings. They are the methodology of choice for
      answering some questions but are not well suited for answering others. In
      particular, they seem poorly suited for answering questions related to why
      therapies work in some situations and not in others and how therapies work in
      general. Ironically, the questions that RCTs cannot answer are the questions that
      are of most interest to clinicians and of most benefit to patients. In this
      paper, we review some of the shortcomings of RCTs and suggest a number of other
      approaches. With a more nuanced understanding of the strengths and weaknesses of
      RCTs and a greater awareness of other research strategies, we might begin to
      develop a more realistic and precise understanding of which treatment options
      would be most effective for particular clients with different problems and in
      different circumstances. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY
      PRACTITIONER MESSAGE: Practitioners can think more critically about evidence
      provided by RCTs and can contribute to progress in psychotherapy by conducting
      research using different methodologies.

PMID- 25601436
TI  - Determination of formulation factors that affect oral medicines acceptability in
      a domiciliary paediatric population.
AB  - Acceptability of medicines for children is a challenge, yet critical to ensure
      adherence to treatment. There is very little literature on formulation factors
      that influence acceptability of medicines, particularly in the domiciliary
      environment. This pragmatic study was conducted at University Hospital Coventry
      and Warwickshire (UHCW) with the aim of identifying the prevalence and nature of
      oral formulation-related barriers to medicines administration in children
      suffering from long-term conditions. This study used semi-structured face-to-face
      interviews with 221 parents/carers of children (0-18 years) and 57 young people
      (12-18 years). RESULT: showed significant medicines refusal and manipulation in
      the domiciliary environment. Nearly one-third (71/232) of respondents reported
      medicines refusal. This was associated significantly with the age of child
      (p=0.016), socioeconomic status (IMD 2010 score) (p=0.002), taste (p<0.001),
      texture (p=0.017), and volume (of liquid/powder) or quantity (of solid dosage
      form) (p<0.001). 29% (74/252) of respondents reported manipulating medicines. P
      values are based on multivariable statistical analysis models. This study has
      indicated that formulations prescribed to children with chronic conditions are
      not meeting the needs of a significant number of patients based on self-report.
      Age-appropriate medicines are required to provide suitable dose units with an
      acceptable taste for children. This study should aid pharmaceutical companies to
      prioritise paediatric formulation work.

PMID- 25601437
TI  - [Short of breath?].

PMID- 25601438
TI  - Ablation therapy of hepatocellular carcinoma: a comparative study between
      radiofrequency and microwave ablation.
AB  - PURPOSE: The aim of the study is to retrospectively evaluate and compare the
      therapeutic response of Radiofrequency (RF) and Microwave (MW) ablation therapy
      of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 53 consecutive patients
      (42 males, 11 females; mean age 59 years, range: 40-68, SD: 4.2) underwent CT
      guided percutaneous RF and MW ablation of 68 HCC liver lesions. The morphologic
      tumor response (number, location and size) was evaluated by magnetic resonance
      imaging. The follow-up protocol was 24 h post-ablation then within 3 monthly
      intervals post-ablation in the first year and 6 monthly intervals thereafter.
      RESULTS: Complete therapeutic response was noted in 84.4% (27/32) of lesions
      treated with RFA and in 88.9% (32/36) of lesions treated with MW ablation (P =
      0.6). Complete response was achieved in all lesions <=2.0 cm in diameter in both
      groups. There was no significant difference in rates of residual foci of HCC
      lesions between RF and MW ablation groups (P = 0.15, Log-rank test). Recurrence
      rate for 3, 6, 9, and 12 months in patients with HCC who underwent RF ablation
      compared with MW ablation were 6.3%, 3.1%, 3.1% versus 0%, 5.6%, 2.8%, and 2.8%.
      Progression-Free Survival rates for treated patients with RF ablation of 1, 2,
      and 3 years were 96.9%, 93.8%, and 90.6% and treated with MW ablation therapy
      were 97.2%, 94.5%, and 91.7, respectively (P = 0.98). CONCLUSION: In conclusion,
      RF and MW ablation therapy showed no significant difference in the treatment of
      HCC regarding the complete response, rates of residual foci of untreated disease,
      and recurrence rate.

PMID- 25601440
TI  - Editorial overview: neurosciences: targeting glutamatergic signaling in CNS
      diseases: new hopes?

PMID- 25601439
TI  - Oxidative stress conditions increase the frequency of de novo formation of the
      yeast [PSI+] prion.
AB  - Prions are self-perpetuating amyloid protein aggregates which underlie various
      neurodegenerative diseases in mammals and heritable traits in yeast. The
      molecular basis of how yeast and mammalian prions form spontaneously into
      infectious amyloid-like structures is poorly understood. We have explored the
      hypothesis that oxidative stress is a general trigger for prion formation using
      the yeast [PSI(+)] prion, which is the altered conformation of the Sup35
      translation termination factor. We show that the frequency of [PSI(+)] prion
      formation is elevated under conditions of oxidative stress and in mutants lacking
      key antioxidants. We detect increased oxidation of Sup35 methionine residues in
      antioxidant mutants and show that overexpression of methionine sulphoxide
      reductase abrogates both the oxidation of Sup35 and its conversion to the
      [PSI(+)] prion. [PSI(+)] prion formation is particularly elevated in a mutant
      lacking the Sod1 Cu,Zn-superoxide dismutase. We have used fluorescence microscopy
      to show that the de novo appearance of [PSI(+)] is both rapid and increased in
      frequency in this mutant. Finally, electron microscopy analysis of native Sup35
      reveals that similar fibrillar structures are formed in both the wild-type and
      antioxidant mutants. Together, our data indicate that oxidative stress is a
      general trigger of [PSI(+) formation, which can be alleviated by antioxidant
      defenses.

PMID- 25601441
TI  - Mukia maderaspatana (Cucurbitaceae) extract-mediated synthesis of silver
      nanoparticles to control Culex quinquefasciatus and Aedes aegypti (Diptera:
      Culicidae).
AB  - Mosquitoes and mosquito-borne diseases are prone to raise health and economic
      impacts. Synthetic insecticide-based interventions are indeed in situations of
      epidemic outbreak and sudden increases of adult mosquitoes. Nanoparticles are
      being used in many commercial applications and were found that aqueous silver
      ions can be reduced by an aqueous extract of plant parts to generate extremely
      stable silver nanoparticles in water. Based on this, silver nanoparticles (SNPs)
      were synthesized using leaf aqueous extract (LAE) of Mukia maderaspatana.
      Further, the synthesized SNPs were characterized by UV-visible spectrum, which
      indicated a strong plasmon resonance at 427 nm. X-ray diffraction (XRD) analysis
      revealed the average crystalline size of the synthesized SNPs was approximately
      64 nm by Debye-Scherrer formulae. Fourier transform infrared (FTIR) spectroscopy
      analysis revealed the presence of different functional groups like amines,
      halides, alkanes, alkynes, amides, and esters with respective stretches, which
      are responsible for the bio-reduction of silver ions. Field emission scanning
      electron microscopy (FESEM) depicted the spherical morphology of SNPs with size
      range of 13-34 nm. The larvicidal activity of LAE and SNPs exhibited an effective
      mortality to Aedes aegypti and Culex quinquefasciatus. The lethal concentration
      (LC50; LC90) of LAE and SNPs were found to be 0.506; 1.082, 0.392; 0.870 ppm and
      0.211; 0.703, 0.094; 0.482 ppm, respectively on A. aegypti and C.
      quinquefasciatus. Thus, the synthesized SNPs have shown preponderant larvicidal
      activity, but further studies are needed to formulate the potential larvicidal
      agents.

PMID- 25601445
TI  - Surgery: palliative primary tumour resection in mCRC-debate continues.

PMID- 25601446
TI  - Image-guided ablation of primary liver and renal tumours.
AB  - Image-guided ablation (IGA) techniques have evolved considerably over the past 20
      years and are increasingly used to definitively treat small primary cancers of
      the liver and kidney. IGA is recommended by most guidelines as the best
      therapeutic choice for patients with early stage hepatocellular carcinoma (HCC)
      defined as either a single tumour smaller than 5 cm or up to three nodules
      smaller than 3 cm-when surgical options are precluded, and has potential as first
      line therapy, in lieu of surgery, for patients with very early stage tumours
      smaller than 2 cm. With regard to renal cell carcinoma, despite the absence of
      any randomized trial comparing the outcomes of IGA with those of standard partial
      nephrectomy, a growing amount of data demonstrate robust oncological outcomes for
      this minimally invasive approach and testify to its potential as a standard-of
      care treatment. Herein, we review the various ablation techniques, the supporting
      evidence, and clinical application of IGA in the treatment of primary liver and
      kidney cancers. 

PMID- 25601442
TI  - Exploiting the critical perioperative period to improve long-term cancer
      outcomes.
AB  - Evidence suggests that the perioperative period and the excision of the primary
      tumour can promote the development of metastases-the main cause of cancer-related
      mortality. This Review first presents the assertion that the perioperative
      timeframe is pivotal in determining long-term cancer outcomes, disproportionally
      to its short duration (days to weeks). We then analyse the various aspects of
      surgery, and their consequent paracrine and neuroendocrine responses, which could
      facilitate the metastatic process by directly affecting malignant tissues, and/or
      through indirect pathways, such as immunological perturbations. We address the
      influences of surgery-related anxiety and stress, nutritional status,
      anaesthetics and analgesics, hypothermia, blood transfusion, tissue damage, and
      levels of sex hormones, and point at some as probable deleterious factors.
      Through understanding these processes and reviewing empirical evidence, we
      provide suggestions for potential new perioperative approaches and interventions
      aimed at attenuating deleterious processes and ultimately improving treatment
      outcomes. Specifically, we highlight excess perioperative release of
      catecholamines and prostaglandins as key deleterious mediators of surgery, and we
      recommend blockade of these responses during the perioperative period, as well as
      other low-risk, low-cost interventions. The measures described in this Review
      could transform the perioperative timeframe from a prominent facilitator of
      metastatic progression, to a window of opportunity for arresting and/or
      eliminating residual disease, potentially improving long-term survival rates in
      patients with cancer.

PMID- 25601447
TI  - Using tumour phylogenetics to identify the roots of metastasis in humans.
AB  - In cancer, much uncertainty remains regarding the origins of metastatic disease.
      Models of metastatic progression offer competing views on when dissemination
      occurs (at an early or late stage of tumour development), whether metastases at
      different sites arise independently and directly from the primary tumour or give
      rise to each other, and whether dynamic cell exchange occurs between
      synchronously growing lesions. Although it is probable that many routes can lead
      to the establishment of systemic disease, clinical observations suggest that
      distinct modes of metastasis might prevail in different tumour types. Gaining a
      more-comprehensive understanding of the evolutionary processes that underlie
      metastasis is not only relevant from a basic biological perspective, but also has
      profound clinical implications. The 'tree of life' of metastatic cancer contains
      answers to many outstanding questions about the development of systemic disease,
      but has only been reconstructed in a limited number of patients. Here we review
      available data on the phylogenetic relationships between primary solid tumours
      and their metastases, and examine to what degree they support different models of
      metastatic progression. We provide a description of experimental methods for
      lineage tracing in human cancer, ranging from broad DNA-sequencing approaches to
      more-targeted techniques, and discuss their respective benefits and caveats.
      Finally, we propose future research questions in the area of cancer
      phylogenetics. 

PMID- 25601449
TI  - Semi-solid tumor model in Xenopus laevis/gilli cloned tadpoles for intravital
      study of neovascularization, immune cells and melanophore infiltration.
AB  - Tumors have the ability to grow as a self-sustaining entity within the body. This
      autonomy is in part accomplished by the tumor cells ability to induce the
      formation of new blood vessels (angiogenesis) and by controlling cell trafficking
      inside the tumor mass. These abilities greatly reduce the efficacy of many cancer
      therapies and pose challenges for the development of more effective cancer
      treatments. Hence, there is a need for animal models suitable for direct
      microscopy observation of blood vessel formation and cell trafficking, especially
      during early stages of tumor establishment. Here, we have developed a reliable
      and cost effective tumor model system in tadpoles of the amphibian Xenopus
      laevis. Tadpoles are ideally suited for direct microscopy observation because of
      their small size and transparency. Using the thymic lymphoid tumor line 15/0
      derived from, and transplantable into, the X. laevis/gilli isogenic clone LG-15,
      we have adapted a system that consists in transplanting 15/0 tumor cells embedded
      into rat collagen under the dorsal skin of LG-15 tadpole recipients. This system
      recapitulates many facets of mammalian tumorigenesis and permits real time
      visualization of the active formation of the tumor microenvironment induced by
      15/0 tumor cells including neovascularization, collagen rearrangements as well as
      infiltration of immune cells and melanophores.

PMID- 25601450
TI  - Ontogeny of the mouse vocal fold epithelium.
AB  - This investigation provides the first systematic determination of the cellular
      and molecular progression of vocal fold (VF) epithelium development in a murine
      model. We define five principal developmental events that constitute the
      progression from VF initiation in the embryonic anterior foregut tube to fully
      differentiated and functional adult tissue. These developmental events include
      (1) the initiation of the larynx and vocal folds with apposition of the lateral
      walls of the primitive laryngopharynx (embryonic (E) day 10.5); (2) the
      establishment of the epithelial lamina with fusion of the lateral walls of the
      primitive laryngopharynx (E11.5); (3) the epithelial lamina recanalization and
      separation of VFs (E13.5-18.5); (4) the stratification of the vocal folds (E13.5
      18.5); and (5) the maturation of vocal fold epithelium (postnatal stages). The
      illustration of these morphogenetic events is substantiated by dynamic changes in
      cell proliferation and apoptosis, as well as the expression pattern of key
      transcription factors, FOXA2, SOX2 and NKX2-1 that specify and pattern the
      foregut endoderm. Furthermore, we documented the gradual conversion of VF
      epithelial cells from simple precursors expressing cytokeratins 8 and 18 in the
      embryo into mature stratified epithelial cells also expressing cytokeratins 5 and
      14 in the adult. Interestingly, in the adult, cytokeratins 5 and 14 appear to be
      expressed in all cell layers in the VF, in contrast to their preferential
      localization to the basal cell layer in surrounding epithelium. To begin
      investigating the role of signaling molecules in vocal fold development, we
      characterized the expression pattern of SHH pathway genes, and how loss of Shh
      affects vocal fold development in the mutant. This study defines the cellular and
      molecular context and serves as the necessary foundation for future functional
      investigations of VF formation. 

PMID- 25601452
TI  - HER3 expression in primary colorectal cancer including corresponding metastases
      in lymph node and liver.
AB  - BACKGROUND: The human epidermal growth factor receptor complex (EGFR-1, HER2,
      HER3 and HER4) plays an important role in pathogenesis of solid tumours. We have
      previously reported high expression of HER3 in 70% of primary colorectal cancer
      (CRC) and that high expression were linked to a worse clinical outcome. The
      purpose of this study is to evaluate the HER3 expression in primary CRC and
      metastases. MATERIAL AND METHODS: Tissue samples from primary CRC, corresponding
      lymph node metastases and liver metastases from 107 patients were analysed by
      immunohistochemistry. RESULTS: Of 107 patients, 80% showed high HER3 expression
      in primary CRC tumours and 81% of the stage III patients presented high
      expression in the lymph node metastases. All patients had liver metastases and
      82% presented high HER3 expression. HER3 expression in primary tumour correlated
      with expression in the corresponding lymph node metastases (r = 0.65, p < 0.001)
      and in the liver metastases (r = 0.45, p < 0.001). A correlation between HER3
      expression in corresponding lymph node and liver metastases (r = 0.65, p < 0.001)
      was seen. CONCLUSION: High HER3 expression is seen in about 80% of primary CRC,
      corresponding lymph node metastases and liver metastases. There is a correlation
      between HER3 expression in primary tumour and metastases in CRC.

PMID- 25601451
TI  - The organizer in evolution-gastrulation and organizer gene expression highlight
      the importance of Brachyury during development of the coral, Acropora millepora.
AB  - Organizer activity, once thought to be restricted to vertebrates, has ancient
      origins. However, among non-bilaterians, it has only been subjected to detailed
      investigation during embryonic development of the sea anemone, Nematostella
      vectensis. As a step toward establishing the extent to which findings in
      Nematostella can be generalized across the large and diverse phylum Cnidaria, we
      examined the expression of some key organizer and gastrulation genes during the
      embryonic development of the coral Acropora millepora. Although anemones and
      corals both belong to the cnidarian class Anthozoa, the two lineages diverged
      during the Cambrian and the morphological development of Acropora differs in
      several important respects from that of Nematostella. While the expression
      patterns of the key genes brachyury, bmp2/4, chordin, goosecoid and forkhead are
      broadly similar, developmental differences between the two species enable novel
      observations, and new interpretations of their significance. Specifically,
      brachyury expression during the flattened prawnchip stage before gastrulation, a
      developmental peculiarity of Acropora, leads us to suggest that it is the key
      gene demarcating ectoderm from endoderm in Acropora, and by implication in other
      cnidarians, whereas previous studies in Nematostella proposed that forkhead plays
      this role. Other novel observations include the transient expression of Acropora
      forkhead in scattered ectodermal cells shortly after gastrulation, and in the
      developing mesenterial filaments, with no corresponding expression reported in
      Nematostella. In addition, the expression patterns of goosecoid and bmp2/4
      confirm the fundamental bilaterality of the Anthozoa. 

PMID- 25601453
TI  - Structurally simple complexes of CO2.
AB  - The ability to bind CO2 through the formation of low-energy, easily-broken, bonds
      could prove invaluable in a variety of chemical contexts. For example, weak bonds
      to CO2 would greatly decrease the cost of the energy-intensive sorbent
      regeneration step common to most carbon capture technologies. Furthermore,
      exploration of this field could lead to the discovery of novel CO2 chemistry.
      Reduction of complexed carbon dioxide might generate chemical feedstocks for the
      preparation of value-added products, particularly transportation fuels or fuel
      precursors. Implementation on a large scale could help to drastically reduce CO2
      concentrations in the atmosphere. However, literature examples of weakly bonded
      complexes of CO2 are relatively few and true coordination complexes to a 'naked'
      CO2 fragment are nearly unheard of. In this review article, a variety of
      complexes of CO2 featuring diverse binding modes and reactivity will be examined.
      Topics covered include: (A) inclusion complexes of CO2 in porous materials. (B)
      Zwitterionic carbamates produced from the reaction of CO2 with polyamines. (C)
      Carbamate salts produced from reaction of CO2 with two equivalents of an amine.
      (D) Insertion products of CO2 into acid-base adducts (e.g., metal complexes). (E)
      Lewis acid-base activated CO2, such as frustrated Lewis pair complexes. (F)
      Simple base-CO2 adducts, wherein the base-CO2 bond is the only interaction
      formed. Complexes in the last category are of particular interest, and include
      imidazol-2-carboxylates (N-heterocyclic carbene adducts of CO2) as well as a few
      other examples that lie outside NHC chemistry. 

PMID- 25601454
TI  - Tolerance of benznidazole in a United States Chagas Disease clinic.
AB  - The US-based Center of Excellence for Chagas Disease performed an observational
      study on the safety and tolerance of benznidazole 5 mg/kg/day for 60 days in 30
      adults with chronic Chagas disease. The side-effect profile was suboptimal,
      including 5 cases of debilitating neuropathy and an unusually high angioedema
      rate. 

PMID- 25601455
TI  - Miltefosine for visceral and cutaneous leishmaniasis: drug characteristics and
      evidence-based treatment recommendations.
AB  - Miltefosine is the only recognized oral agent with potential to treat
      leishmaniasis. Miltefosine had demonstrated very good cure rates for visceral
      leishmaniasis (VL) in India, Nepal, and Bangladesh, but high rates of clinical
      failures have been recently reported. Moderate efficacy has been observed for VL
      in East Africa, whereas data from Mediterranean countries and Latin America are
      scarce. Results have not been very promising for patients coinfected with VL and
      human immunodeficiency virus. However, miltefosine's long half-life and its oral
      administration could make it a good option for maintenance prophylaxis. Good
      evidence of efficacy has been documented in Old World cutaneous leishmaniasis
      (CL), and different cure rates among New World CL have been obtained depending on
      the geographical areas and species involved. Appropriate regimens for New World
      mucocutaneous leishmaniasis need to be established, although longer treatment
      duration seems to confer better results. Strategies to prevent the development
      and spread of miltefosine resistance are urgently needed. 

PMID- 25601457
TI  - 4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the
      platypus (Ornithorhynchus anatinus) and its evolutionary significance.
AB  - Monotremes (echidnas and platypus) retain an ancestral form of reproduction: egg
      laying followed by secretion of milk onto skin and hair in a mammary patch, in
      the absence of nipples. Offspring are highly immature at hatching and depend on
      oligosaccharide-rich milk for many months. The primary saccharide in long-beaked
      echidna milk is an acidic trisaccharide Neu4,5Ac2(alpha2-3)Gal(beta1-4)Glc (4-O
      acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized
      in platypus milk. In this study, acidic oligosaccharides purified from the
      carbohydrate fraction of platypus milk were characterized by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry and (1)H-nuclear
      magnetic resonance spectroscopy. All identified structures, except Neu5Ac(alpha2
      3)Gal(beta1-4)Glc (3'-sialyllactose) contained Neu4,5Ac2 (4-O-acetyl-sialic
      acid). These include the trisaccharide 4-O-acetyl 3'-sialyllactose, the
      pentasaccharide Neu4,5Ac2(alpha2-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (4
      O-acetyl-3'-sialyllacto-N-tetraose d) and the hexasaccharide Neu4,5Ac2(alpha2
      3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc (4-O-acetyl-3'
      sialyllacto-N-fucopentaose III). At least seven different octa- to deca
      oligosaccharides each contained a lacto-N-neohexaose core (LNnH) and one or two
      Neu4,5Ac2 and one to three fucose residues. We conclude that platypus milk
      contains a diverse (>= 20) array of neutral and acidic oligosaccharides based
      primarily on lactose, lacto-N-neotetraose (LNnT) and LNnH structural cores and
      shares with echidna milk the unique feature that all identified acidic
      oligosaccharides (other than 3'-sialyllactose) contain the 4-O-acetyl-sialic acid
      moiety. We propose that 4-O-acetylation of sialic acid moieties protects acidic
      milk oligosaccharides secreted onto integumental surfaces from bacterial
      hydrolysis via steric interference with bacterial sialidases. This may be of
      evolutionary significance since taxa ancestral to monotremes and other mammals
      are thought to have secreted milk, or a milk-like fluid containing
      oligosaccharides, onto skin surfaces.

PMID- 25601456
TI  - Incidence of herpes zoster in HIV-infected adults in the combined antiretroviral
      therapy era: results from the FHDH-ANRS CO4 cohort.
AB  - BACKGROUND: Recent studies have shown a decrease in the incidence of herpes
      zoster (HZ) among human immunodeficiency virus (HIV)-infected patients since the
      combined antiretroviral therapy (cART) era, but more data are needed on a
      possible increase in the risk early after cART initiation. METHODS: We studied HZ
      incidence and risk factors among patients followed in the French Hospital
      Database on HIV (FHDH) between 1992 and 2011. Standardized incidence ratios
      (SIRs) were used for comparison with the general population between 2005 and
      2008. The risk of HZ following cART initiation (0-5 and >=6 months) was studied
      with Poisson regression models. RESULTS: A total of 7167 cases of incident HZ
      were diagnosed among 91 044 individuals (583 125 person-years [PY]). The
      incidence declined significantly, from 2955 per 100 000 PY in 1992-1996 to 628
      per 100 000 PY in 2009-2011. This decline was mainly explained by cART (relative
      risk [RR], 0.60; 95% confidence interval {CI}, .57-.64). The risk of HZ was
      associated with low CD4 cell counts, high HIV RNA levels, low CD4/CD8 ratios, and
      prior AIDS. Compared to the general population, the risk of HZ was higher in HIV
      infected patients (overall SIR, 2.7; 95% CI, 2.6-2.9), particularly those aged 15
      44 years (SIR, 4-6). In ART-naive patients, a moderate increase in the HZ risk
      was observed during the first 6 months of cART, with a peak at 3 months (RR,
      1.47; 95% CI, 1.26-1.73), a finding that disappeared after adjustment for the
      current CD4 cell count (RR, 1.03; 95% CI, .81-1.32). CONCLUSIONS: The risk of HZ
      has declined markedly among HIV-infected patients in the cART era, but remains 3
      times higher than in the general population. The risk increases moderately during
      the first 6 months of cART.

PMID- 25601458
TI  - Time to Guideline-Based Empiric Antibiotic Therapy in the Treatment of Pneumonia
      in a Community Hospital: A Retrospective Review.
AB  - PURPOSE: The 2005 American Thoracic Society/Infectious Diseases Society of
      America (ATS/IDSA) guidelines for hospital-acquired pneumonia (HAP), ventilator
      associated pneumonia (VAP), and health care-associated pneumonia (HCAP) stress
      the importance of initiating prompt appropriate empiric antibiotic therapy. This
      study's purpose was to determine the percentage of patients with HAP, VAP, and
      HCAP who received guideline-based empiric antibiotic therapy and to determine the
      average time to receipt of an appropriate empiric regimen. METHODS: A
      retrospective chart review of adults with HAP, VAP, or HCAP was conducted at a
      community hospital in suburban Birmingham, Alabama. The hospital's electronic
      medical record system utilized International Classification of Diseases, Ninth
      Revision (ICD-9) codes to identify patients diagnosed with pneumonia. The
      percentage of patients who received guideline-based empiric antibiotic therapy
      was calculated. The mean time from suspected diagnosis of pneumonia to initial
      administration of the final antibiotic within the empiric regimen was calculated
      for patients who received guideline-based therapy. RESULTS: Ninety-three patients
      met the inclusion criteria. The overall guideline adherence rate for empiric
      antibiotic therapy was 31.2%. The mean time to guideline-based therapy in
      hours:minutes was 7:47 for HAP and 28:16 for HCAP. For HAP and HCAP combined, the
      mean time to appropriate therapy was 21:55. CONCLUSION: Guideline adherence rates
      were lower and time to appropriate empiric therapy was greater for patients with
      HCAP compared to patients with HAP.

PMID- 25601459
TI  - Short-term and long-term storage stability of heparin plasma ammonia.
AB  - AIMS: Ammonia is an extremely unstable analyte and requires special attention
      during sampling, transport and storage. The aim of this study was to evaluate the
      stability of ammonia in lithium-heparin plasma during short-term (at +4 degrees
      C) and long-term (at -20 degrees C) storage. METHODS: Twenty plasma samples were
      used for short-term stability assessment. Each sample was divided into five
      aliquots and stored in stoppered tubes at +4 degrees C, for 1, 2, 3, 4 and 24 h
      from initial testing. Fifteen plasma samples were used for long-term stability
      assessment. Each sample was divided into eight aliquots and stored in stoppered
      tubes at -20 degrees C for 3, 24, 48 h and 1, 2, 4, 8 and 12 weeks from initial
      testing. Ammonia concentration was determined on a Beckman Coulter AU2700
      chemistry analyser using Randox ammonia enzymatic UV method. Bias was calculated
      from initial value for each time point and compared with quality specifications
      defined by Royal College of Pathologists of Australasia. RESULTS: The average
      bias exceeded the total allowable error after storage of samples for 1 h at +4
      degrees C and 3 h at -20 degrees C. CONCLUSION: Ammonia is not stable during
      storage at +4 degrees C and -20 degrees C in lithium-heparinised plasma and
      should therefore be analysed immediately.

PMID- 25601462
TI  - More doctors should be trained in identifying female genital mutilation in
      children, says judge.

PMID- 25601460
TI  - Elimination of unfit cells maintains tissue health and prolongs lifespan.
AB  - Viable yet damaged cells can accumulate during development and aging. Although
      eliminating those cells may benefit organ function, identification of this less
      fit cell population remains challenging. Previously, we identified a molecular
      mechanism, based on "fitness fingerprints" displayed on cell membranes, which
      allows direct fitness comparison among cells in Drosophila. Here, we study the
      physiological consequences of efficient cell selection for the whole organism. We
      find that fitness-based cell culling is naturally used to maintain tissue health,
      delay aging, and extend lifespan in Drosophila. We identify a gene, azot, which
      ensures the elimination of less fit cells. Lack of azot increases morphological
      malformations and susceptibility to random mutations and accelerates tissue
      degeneration. On the contrary, improving the efficiency of cell selection is
      beneficial for tissue health and extends lifespan. 

PMID- 25601461
TI  - Extracellular metabolic energetics can promote cancer progression.
AB  - Colorectal cancer primarily metastasizes to the liver and globally kills over
      600,000 people annually. By functionally screening 661 microRNAs (miRNAs) in
      parallel during liver colonization, we have identified miR-551a and miR-483 as
      robust endogenous suppressors of liver colonization and metastasis. These miRNAs
      convergently target creatine kinase, brain-type (CKB), which phosphorylates the
      metabolite creatine, to generate phosphocreatine. CKB is released into the
      extracellular space by metastatic cells encountering hepatic hypoxia and
      catalyzes production of phosphocreatine, which is imported through the SLC6A8
      transporter and used to generate ATP-fueling metastatic survival. Combinatorial
      therapeutic viral delivery of miR-551a and miR-483-5p through single-dose adeno
      associated viral (AAV) delivery significantly suppressed colon cancer metastasis,
      as did CKB inhibition with a small-molecule inhibitor. Importantly, human liver
      metastases express higher CKB and SLC6A8 levels and reduced miR-551a/miR-483
      levels relative to primary tumors. We identify the extracellular space as an
      important compartment for malignant energetic catalysis and therapeutic
      targeting.

PMID- 25601463
TI  - Sonothrombolysis: the contribution of stable and inertial cavitation to clot
      lysis.
AB  - Microbubble-mediated sonothrombolysis (STL) is a remarkable approach to vascular
      occlusion therapy. However, STL remains a complex process with multiple
      interactions between clot, ultrasound (US), microbubbles (MB) and thrombolytic
      drug. The aim of this study was to evaluate the ability of combining US and MB to
      degrade fibrin and, more specifically, to assess the roles of both stable (SC)
      and inertial (IC) cavitation. Human blood clots containing radiolabeled fibrin
      were exposed to different combinations of recombinant tissue plasminogen
      activator (rtPA), US (1 MHz) and phospholipid MB. Three acoustic pressures were
      tested: 200, 350 and 1,300 kPa (peak-negative pressure). Clot lysis was assessed
      by diameter loss and release of radioactive fibrin degradation products. The
      combination rtPA + US + MB clearly revealed that IC (1,300 kPa) was able to
      enhance fibrin degradation significantly (66.3 +/- 1.8%) compared with rtPA alone
      (51.7 +/- 2.0%, p < 0.001). However, SC failed to enhance fibrin degradation at
      an acoustic pressure of 200 kPa. At 350 kPa, a synergistic effect between rtPA
      and US + MB was observed with an absolute increase of 6% compared to rtPA alone
      (p < 0.001). Conversely, without rtPA, the combination of US + MB was unable to
      degrade the fibrin network (0.3 +/- 0.1%, p > 0.05 vs. control), but induced a
      distinct loss of red blood cells throughout the entire thickness of the clot,
      implying that MB were able to penetrate and cavitate inside the clot.

PMID- 25601464
TI  - Still water runs deep.

PMID- 25601465
TI  - Understanding nutritional interventions and physical exercise in non-alcoholic
      fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in
      adults and its prevalence is rising around the world. This pathology is
      characterized by accumulation of liver fat, which exceeds 5% of liver weight in
      absence of alcohol consumption, viral infection or other hepatic etiology. Since
      NAFLD has been associated with obesity, insulin resistance, diabetes or
      alteration of lipid profiles, it is considered as the liver manifestation of
      metabolic syndrome. Pathogenic mechanisms of NAFLD have not been clearly
      elucidated, but different events such as lipid accumulation, insulin resistance,
      oxidative and endoplasmic reticulum stress, mitochondrial dysfunction and
      inflammation are involved. Modifications in lifestyle constitute the first line
      for the management of NAFLD. Nutritional interventions include low fat and
      carbohydrate diet with higher polyunsaturated fatty acids ingestion. Moreover,
      supplementation with antioxidant and cytoprotective agents could be useful to
      decrease oxidative stress, inflammation and fibrosis. Physical activity enables
      to reduce the expression of lipogenic genes, fat accumulation, or insulin
      resistance and improves cardiorespiratory fitness. Benefits have been found
      following both aerobic exercise and resistance training, and remain even after
      exercise cessation. However, more studies are required to analyze the molecular
      and cellular mechanisms involved in nutritional and physical intervention, and to
      define the volume of activity required and its association with weight loss. In
      this paper, we offer an updated overview of the mechanisms implicated in the
      progression of NAFLD, and analyze the beneficial effects of nutritional
      interventions and physical exercise in the prevention and treatment of this
      condition. 

PMID- 25601466
TI  - Intracellular signaling of the aging suppressor protein Klotho.
AB  - The Klotho protein deficiency is known to participate in premature aging. As an
      aging suppressor, Klotho is an important molecule in aging processes and its
      overexpression results in longevity. Due to many reasons, the insulin/insulin
      like growth factor-1 (IGF-1) has been considered as a key pathway in aging
      research. The Klotho gene is closely related to this pathway. The Klotho gene
      encodes a transmembrane protein that after cleavage is also found as a secreted
      protein. Importantly, its overexpression suppresses insulin/IGF-1 signaling and
      thus extends the lifespan. In addition, Klotho participates in the regulation of
      several other intracellular signaling pathways, including regulation of FGF23
      signaling, cAMP, PKC, transforming growth factor-beta (TGF-beta), p53/p21, and
      Wnt signaling. The aim of this review is to summarize current literature that
      shows the involvement of Klotho in the regulation of several intracellular
      pathways. The results of our review clearly indicate that Klotho participates in
      several intracellular signaling pathways, and by regulating them, Klotho is
      involved in aging and longevity. 

PMID- 25601467
TI  - Small heat shock proteins and the endoplasmic reticulum: potential attractive
      therapeutic targets?
AB  - The endoplasmic reticulum(ER) is crucial for protein and lipid synthesis, folding
      and cellular homeostasis. Function impairment of ER would induce ER stress, which
      might play an important role in many different pathological states. Small heat
      shock proteins (sHsps) are known to be widely expressed throughout many tissues.
      SHsps are found to regulate many different pathological and pathophysiological
      processes and they are supposed to be potential therapeutic targets. Recent
      studies indicate that multiple sHsps localize to the mammalian and plant ER and
      sHsps confer protection against ER stress in multiple cellular processes. The
      mechanisms responsible for the cytoprotective effects of sHsps are related to
      maintaining ER homeostasis. Improved understanding of sHsps-related
      cytoprotective action on ER and successful strategies which could specifically
      target components of ER stress signalling responses amelioration of their toxic
      effects by sHsps is of great importance in the development of therapeutic
      approach for the disorders induced by dysfunction of ER. 

PMID- 25601468
TI  - Emerging role for alphaB-crystallin as a therapeutic agent: pros and cons.
AB  - HSPB5 or alphaB-crystallin (alphaBC) is a major protein of the vertebrate eye
      lens belonging to the small heat-shock protein family of proteins that respond to
      various stressful conditions. alphaBC also is found outside the lens in various
      non-ocular tissues and acts as a molecular chaperone by preventing aggregation of
      proteins, inhibits apoptosis and inflammation, and maintains cytoskeletal
      architecture. The alphaBC protein is phosphorylated on three serine residues S59,
      S45, and S19, and several functions of alphaBC are modulated by phosphorylation.
      Numerous studies have revealed the upregulation of alphaBC in pathological
      conditions such as neurodegenerative diseases, cancers, diabetes, retinal
      diseases, cataracts, ischemia/repurfusion, aging, and others. However, it is
      unknown whether the up-regulation of alphaBC is causative or protective for these
      pathological conditions. Although alphaBC has been shown to provide a protective
      effect in neurodegenerative diseases, inflammation, diabetes, and retinal
      diseases, other studies have described a deleterious role of alphaBC in cancers
      and pulmonary fibrosis. The therapeutic potential of alphaBC alone or in
      combination with alphaA-crystallin has been reported. Acetylated alphaBC peptides
      have been shown to be more potent than native alphaBC for chaperone as well as
      therapeutic activities using both in vitro and in vivo models. Further, for
      efficient delivery of alpha BC into cells, carrier molecules such as
      polylacticcoglycolic acid, polycaprolactone and cell penetration peptides have
      been used. In this review, we have summarized current data from emerging and
      exciting studies of the therapeutic strategies of alpha BC and alpha BC peptides
      and the efficient delivery strategies of these proteins in various disease
      models, including neurodegenerative diseases, retinal diseases, platelet
      aggregation, inflammation, and ischemia. 

PMID- 25601469
TI  - Serotonin and cancer: what is the link?
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine that acts as a
      neurotransmitter in the central nervous system, local mediator in the gut and
      vasoactive agent in the blood. Serotonin exerts its multiple, sometimes opposing
      actions through interaction with a multiplicity of receptors coupled to various
      signalling pathways. In addition to its well-known functions, serotonin has been
      shown to be a mitogenic factor for a wide range of normal and tumoral cells.
      Serotonin exhibits a growth stimulatory effect in aggressive cancers and
      carcinoids more often through 5- HT1 and 5-HT2 receptors. In contrast, low doses
      of serotonin can inhibit tumour growth via the decrease of blood supply to the
      tumour, suggesting that the role of serotonin on tumour growth is concentration
      dependent. Data are also available on serotonin involvement in cancer cell
      migration, metastatic processes and as a mediator of angiogenesis. Moreover, the
      progression of some tumours is accompanied by a dysregulation of the pattern of
      serotonin receptor expressions. Serum serotonin level was found to be suitable
      for prognosis evaluation of urothelial carcinoma in the urinary bladder,
      adenocarcinoma of the prostate and renal cell carcinoma. In some cases,
      antagonists of serotonin receptors, inhibitors of selective serotonin transporter
      and of serotonin synthesis have been successfully used to prevent cancer cell
      growth. This review revaluates serotonin involvement in several types of cancer
      and at different stages of their progression. 

PMID- 25601470
TI  - Immune tolerance elicited via unique ocular and oral routes.
AB  - Immune tolerance can be induced by numerous methods. This review article aims to
      draw lines of similarity and contrast between two unique models of immune
      tolerance, namely Anterior Chamber Associated Immune Deviation (ACAID) and Nickel
      induced oral tolerance. ACAID is an immune tolerance model that leads to the
      generation of CD4(+) T regulatory cells and CD8(+) T regulatory cells in the
      periphery after the injection of an antigen into the anterior chamber of the eye.
      Nickel-induced oral tolerance is another immune tolerance model that is induced
      by the contact allergen Nickel and leads to the generation of Nickel-specific
      CD4(+) CD25(+) T regulatory cells after oral exposure. The goal of comparing
      different models of immune tolerance is to identify which mechanisms are
      universal and which mechanisms are model-specific. The knowledge of such
      mechanisms would allow scientists and clinicians to better intervene in different
      immune deregulation scenarios. 

PMID- 25601471
TI  - Targeting the PI3K/AKT/mTOR signaling pathway in medulloblastoma.
AB  - Medulloblastoma is the most common malignant childhood brain tumor and is
      associated with a poor outcome. There is an urgent need to develop novel targeted
      therapeutic approaches for medulloblastoma, which will arise from an enhanced
      understanding of the disease at the molecular level. Medulloblastoma has been
      recognized to be a heterogeneous disease, and no recurrent cancer gene mutations
      have been found, although many of the mutations described so far affect key
      intracellular signaling pathways, such as sonic hedgehog (SHH) and Wnt/beta
      catenin. The PI3K/AKT/mTOR (PAM) signaling pathway controls key cellular
      responses, such as cell growth and proliferation, survival, migration and
      metabolism. Over the last decades, it has been recognized that this intracellular
      signaling pathway is frequently activated by genetic and epigenetic alterations
      in malignant brain tumors, including medulloblastoma. Clinical trials have
      started to evaluate the safety and efficacy of agents targeting this pathway in
      malignant brain tumors. Due to the complexity of the PAM signaling pathway, there
      remain significant difficulties in the development of novel therapeutic
      approaches. The future challenges in developing effective treatments for cancer
      patients include the development of predictive biomarkers and combinatorial
      approaches to effectively target multiple signal transduction pathways. In this
      review article, we will summarize the current knowledge about the role of PAM
      signaling in medulloblastoma and discuss the strategies that are currently being
      evaluated with targeted agents against this pathway. 

PMID- 25601472
TI  - Long noncoding RNA GAS5: a novel marker involved in glucocorticoid response.
AB  - Glucocorticoids (GCs) exert their effects through regulation of gene expression
      after activation in the cytoplasm of the glucocorticoid receptor (GR) encoded by
      NR3C1 gene. A negative feedback mechanism resulting in GR autoregulation has been
      demonstrated through the binding of the activated receptor to intragenic
      sequences called GRE-like elements, contained in GR gene. The long noncoding RNA
      growth arrest-specific transcript 5 (GAS5) interacts with the activated GR
      suppressing its transcriptional activity. The aim of this study was to evaluate
      the possible role of GAS5 and NR3C1 gene expression in the antiproliferative
      effect of methylprednisolone in peripheral blood mononuclear cells and to
      correlate the expression with individual sensitivity to GCs. Subjects being poor
      responders to GCs presented higher levels of GAS5 and NR3C1 in comparison with
      good responders. We suggest that abnormal levels of GAS5 may alter GC
      effectiveness, probably interfering with the mechanism of GR autoregulation. 

PMID- 25601473
TI  - Wip1-deficient neutrophils significantly promote intestinal ischemia/reperfusion
      injury in mice.
AB  - Wip1 is a serine/threonine protein phosphatase which plays a critical role in
      neutrophil development and maturation. In the present study, we used a neutrophil
      dependent model of intestinal ischemia/reperfusion (I/R) injury to identify the
      role of Wip1 in neutrophil function under the condition of oxidative stress and
      inflammation. Wip1- deficient mice displayed more severe intestinal I/R injury
      with increased infiltration of neutrophils and higher expression of chemokines
      like CXCL-1, CXCL-2 and CCL-2, as well as inflammatory cytokine like TNF-alpha
      and IL-17. Studies in Wip1KOa->WT full hematopoietic chimera mice showed that
      Wip1 intrinsically regulated the function of immune cells after intestinal I/R
      injury. Through adoptive transfer of neutrophils from WT mice or mice with
      deficiency of IL-17, IL-17/Wip1 or Wip1, we demonstrated that Wip1KO neutrophils
      produced more IL-17 and eventually led to more severe intestinal I/R injury.
      Thus, our findings identify Wip1 as an intrinsic negative regulator of neutrophil
      inflammation in intestinal I/R injury process.

PMID- 25601474
TI  - Tear functions in patients with vitiligo.
AB  - BACKGROUND: Vitiligo is a common, acquired, pigmentary disorder characterized by
      the loss of melanocytes. In this study, we evaluated the ophthalmalogic
      abnomalies of patients with vitiligo with regard to tear functions. METHODS: The
      patients and control subjects underwent examinations via the Schirmer's test,
      tear film break-up time (BUT), and Rose Bengal staining. RESULTS: Schirmer test
      values in patients with vitiligo were lower than those in the control subjects,
      but the differences were not statistically significant (P = 0.200). In addition,
      the BUT values of patients with vitiligo were also significantly lower (P <
      0.001), and the Rose Bengal scores of patients with vitiligo were significantly
      higher (P < 0.001) than the scores of the control subjects. When comparing only
      the vitiligo subgroups, the Schirmer test scores and BUT values of patients with
      acrofacial vitiligo were significantly lower than those of patients with
      generalized vitiligo (P = 0.001). Furthermore, the Rose Bengal scores of patients
      with acrofacial vitiligo were significantly higher than the scores of patients in
      the generalized subgroup (P = 0.011). CONCLUSION: This study revealed that there
      is a decrease in tear production in patients with vitiligo, particularly in those
      with the acrofacial type of vitiligo.

PMID- 25601475
TI  - A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated
      repression at the INK4 locus.
AB  - Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and
      function. Senescence, a strong anti-proliferative process and a major anticancer
      barrier, is associated with dramatic chromatin reorganization in heterochromatin
      foci. Here we analyze strand-specific transcriptome changes during oncogene
      induced human senescence. Strikingly, while differentially expressed RNAs are
      mostly repressed during senescence, ncRNAs belonging to the recently described
      vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that
      VAD, a novel antisense vlincRNA strongly induced during senescence, is required
      for the maintenance of senescence features. VAD modulates chromatin structure in
      cis and activates gene expression in trans at the INK4 locus, which encodes cell
      cycle inhibitors important for senescence-associated cell proliferation arrest.
      Importantly, VAD inhibits the incorporation of the repressive histone variant
      H2A.Z at INK4 gene promoters in senescent cells. Our data underline the
      importance of vlincRNAs as sensors of cellular environment changes and as
      mediators of the correct transcriptional response. 

PMID- 25601477
TI  - Impact of immersion oils and mounting media on the confocal imaging of dendritic
      spines.
AB  - BACKGROUND: Structural plasticity, such as changes in dendritic spine morphology
      and density, reflect changes in synaptic connectivity and circuitry. Procedural
      variables used in different methods for labeling dendritic spines have been
      quantitatively evaluated for their impact on the ability to resolve individual
      spines in confocal microscopic analyses. In contrast, there have been
      discussions, though no quantitative analyses, of the potential effects of
      choosing specific mounting media and immersion oils on dendritic spine
      resolution. NEW METHOD: Here we provide quantitative data measuring the impact of
      these variables on resolving dendritic spines in 3D confocal analyses. Medium
      spiny neurons from the rat striatum and nucleus accumbens are used as examples.
      RESULTS: Both choice of mounting media and immersion oil affected the
      visualization of dendritic spines, with choosing the appropriate immersion oil as
      being more imperative. These biologic data are supported by quantitative measures
      of the 3D diffraction pattern (i.e. point spread function) of a point source of
      light under the same mounting medium and immersion oil combinations. COMPARISON
      WITH EXISTING METHOD: Although not a new method, this manuscript provides
      quantitative data demonstrating that different mounting media and immersion oils
      can impact the ability to resolve dendritic spines. These findings highlight the
      importance of reporting which mounting medium and immersion oil are used in
      preparations for confocal analyses, especially when comparing published results
      from different laboratories. CONCLUSION: Collectively, these data suggest that
      choosing the appropriate immersion oil and mounting media is critical for
      obtaining the best resolution, and consequently more accurate measures of
      dendritic spine densities.

PMID- 25601478
TI  - Modified Richardson's method versus the box-counting method in neuroscience.
AB  - BACKGROUND: The morphology of dendrites, including apical dendrites of pyramidal
      neurons, is already well-known. However, the quantification of their complexity
      still remains open. Fractal analysis has proven to be a valuable method of
      analyzing the degree of complexity of dendrite morphology. NEW METHOD:
      Richardson's method is a technique of measuring the fractal dimension of open and
      closed lines of objects. This method was modified in order to measure the fractal
      dimension of neuronal arborization. The focus of this experiment was on the
      apical dendrites of superficial and deep pyramidal neurons in the rat cerebral
      cortex. RESULTS: Apical dendrites of superficial cortical pyramidal neurons have
      a higher mean value of the fractal dimension as compared to deep pyramidal
      neurons. COMPARISON WITH EXISTING METHOD: Using the modified Richardson's method
      we showed that the mean value of the fractal dimension of apical dendrites in
      superficial pyramidal neurons is highly statistically significant as compared to
      the value of the fractal dimension in deep pyramidal neurons. On the other hand,
      the mean values of the fractal dimension between the same groups of apical
      dendrites measured by the most popular box-counting method showed merely a
      statistically significant difference. CONCLUSION: The modified Richardson's
      method of fractal analysis is an efficient mathematical method for calculating
      the fractal dimension of dendrites and could be used in order to calculate the
      complexity of dendrite arborization.

PMID- 25601476
TI  - A new approach for optical assessment of directional anisotropy in turbid media.
AB  - A study of polarized light transport in scattering media exhibiting directional
      anisotropy or linear birefringence is presented in this paper. Novel theoretical
      and experimental methodologies for the quantification of birefringent alignment
      based on out-of-plane polarized light transport are presented here. A polarized
      Monte Carlo model and a polarimetric imaging system were devised to predict and
      measure the impact of birefringence on an impinging linearly polarized light
      beam. Ex-vivo experiments conducted on bovine tendon, a biological sample
      consisting of highly packed type I collagen fibers with birefringent property,
      showed good agreement with the analytical results.

PMID- 25601480
TI  - Malignant degeneration of scars in elderly people (Marjolin's ulcers).

PMID- 25601479
TI  - Highly sensitive and multifunctional tactile sensor using free-standing ZnO/PVDF
      thin film with graphene electrodes for pressure and temperature monitoring.
AB  - We demonstrate an 80-MUm-thick film (which is around 15% of the thickness of the
      human epidermis), which is a highly sensitive hybrid functional gauge sensor, and
      was fabricated from poly(vinylidene fluoride) (PVDF) and ZnO nanostructures with
      graphene electrodes. Using this film, we were able to simultaneously measure
      pressure and temperature in real time. The pressure was monitored from the change
      in the electrical resistance via the piezoresistance of the material, and the
      temperature was inferred based on the recovery time of the signal. Our thin film
      system enabled us to detect changes in pressure as small as 10 Pa which is
      pressure detection limit was 10(3)-fold lower than the minimum level required for
      artificial skin, and to detect temperatures in the range 20-120  degrees C.

PMID- 25601481
TI  - A reduction for spiking integrate-and-fire network dynamics ranging from
      homogeneity to synchrony.
AB  - In this paper we provide a general methodology for systematically reducing the
      dynamics of a class of integrate-and-fire networks down to an augmented 4
      dimensional system of ordinary-differential-equations. The class of integrate-and
      fire networks we focus on are homogeneously-structured, strongly coupled, and
      fluctuation-driven. Our reduction succeeds where most current firing-rate and
      population-dynamics models fail because we account for the emergence of 'multiple
      firing-events' involving the semi-synchronous firing of many neurons. These
      multiple-firing-events are largely responsible for the fluctuations generated by
      the network and, as a result, our reduction faithfully describes many dynamic
      regimes ranging from homogeneous to synchronous. Our reduction is based on first
      principles, and provides an analyzable link between the integrate-and-fire
      network parameters and the relatively low-dimensional dynamics underlying the 4
      dimensional augmented ODE. 

PMID- 25601483
TI  - Community translation of the Math Interactive Learning Experience Program for
      children with FASD.
AB  - The Math Interactive Learning Experience (MILE), a program designed to address
      academic and behavioral problems found in children with Fetal Alcohol Spectrum
      Disorders (FASD), was found to be effective in a randomized clinical trials with
      results that persisted at a 6-month follow-up. The current study evaluated the
      effectiveness of a community translation, in partnership with several community
      sites in the metropolitan Atlanta area. A total of 60 participants were randomly
      assigned to one of the three treatment groups: the MILE program administered at a
      specialty care center (Center MILE) or in the community (Community MILE), or to
      parent math instruction only (Parent Instruction). This study evaluated
      instructor satisfaction with the training program, knowledge related to FASD and
      the MILE program, adherence to the MILE teaching methodology, participant math
      outcomes, and parents' satisfaction with their treatment experience. Instructors
      reported a high degree of satisfaction with the overall training and mean site
      fidelity ratings were positively correlated with change in math performance.
      Those in the MILE intervention groups demonstrated more positive gains in math
      skills than those in the Parent Instruction group but did not differ from each
      other. Parents in the Parent Instruction group reported less satisfaction with
      their intervention than those assigned to the Center MILE group but satisfaction
      ratings did not differ between those in the MILE intervention groups. These
      results indicate that the community translation and the MILE instructor training
      program developed as part of this process were well-received and effective in
      producing positive treatment outcomes. 

PMID- 25601482
TI  - Effects of spike-triggered negative feedback on receptive-field properties.
AB  - Sensory neurons are often described in terms of a receptive field, that is, a
      linear kernel through which stimuli are filtered before they are further
      processed. If information transmission is assumed to proceed in a feedforward
      cascade, the receptive field may be interpreted as the external stimulus' profile
      maximizing neuronal output. The nervous system, however, contains many feedback
      loops, and sensory neurons filter more currents than the ones representing the
      transduced external stimulus. Some of the additional currents are generated by
      the output activity of the neuron itself, and therefore constitute feedback
      signals. By means of a time-frequency analysis of the input/output
      transformation, here we show how feedback modifies the receptive field. The model
      is applicable to various types of feedback processes, from spike-triggered
      intrinsic conductances to inhibitory synaptic inputs from nearby neurons. We
      distinguish between the intrinsic receptive field (filtering all input currents)
      and the effective receptive field (filtering only external stimuli). Whereas the
      intrinsic receptive field summarizes the biophysical properties of the neuron
      associated to subthreshold integration and spike generation, only the effective
      receptive field can be interpreted as the external stimulus' profile maximizing
      neuronal output. We demonstrate that spike-triggered feedback shifts low-pass
      filtering towards band-pass processing, transforming integrator neurons into
      resonators. For strong feedback, a sharp resonance in the spectral neuronal
      selectivity may appear. Our results provide a unified framework to interpret a
      collection of previous experimental studies where specific feedback mechanisms
      were shown to modify the filtering properties of neurons. 

PMID- 25601484
TI  - Future options for ALK-positive non-small cell lung cancer.
AB  - Recent advances in the understanding of non-small cell lung cancer (NSCLC)
      biology have revealed a number of 'targetable' genetic alterations that underlie
      cancer growth and survival in specific patients subgroups. The anaplastic
      lymphoma kinase (ALK) gene rearrangement identifies a population of NSCLCs in
      whom dysregulation of ALK-tyrosine kinase (-TK) leads to uncontrolled
      proliferation of cancer cells, thus providing the basis for the therapeutic use
      of ALK-TK inhibitors (-TKIs) in ALK-rearranged (-positive) disease. Crizotinib
      was the first ALK-TKI to undergo clinical development in ALK-positive advanced
      NSCLC, in which it has been shown to greatly outperform the best available
      chemotherapy regimen in either second- or first-line setting. More recently, the
      novel second-generation ALK-TKI ceritinib has been shown to be highly active in
      either crizotinib-pretreated or -naive population. Nevertheless, as mechanisms of
      resistance to crizotinib and ALK-TKIs in general are being progressively
      elucidated, the treatment landscape of ALK-positive NSCLC is expected to evolve
      rapidly. In the present review we will briefly discuss the current knowledge of
      ALK-positive advanced non-small cell lung cancer. Also, we will touch upon new
      developments on drugs/combination regimens aimed at inhibiting the ALK-TK, in an
      attempt to delineate how treatment of ALK-positive disease may change in the next
      future. 

PMID- 25601485
TI  - Targeting HER2 in the treatment of non-small cell lung cancer.
AB  - Oncogenic driver mutations have emerged as major treatment targets for molecular
      therapies in a variety of cancers. HER2 positivity has been well-studied in
      breast cancer, but its importance is still being explored in non-small cell lung
      cancer (NSCLC). Laboratory methods for assessment of HER2 positivity in NSCLC
      include immunohistochemistry (IHC) for protein overexpression, fluorescent in
      situ hybridization (FISH) for gene amplification, and next generation sequencing
      (NGS) for gene mutations. The prognostic and predictive significance of these
      tests remain to be validated, with an emerging association between HER2 gene
      mutations and response to HER2 targeted therapies. Despite the assay used to
      determine the HER2 status of lung tumors, all patients with advanced HER2
      positive lung adenocarcinoma should be evaluated for treatment with targeted
      agents. Several clinical approaches for inclusion of these drugs into patient
      treatment plans exist, but there is no defined algorithm specific to NSCLC. 

PMID- 25601486
TI  - Role of nicotinic acetylcholine receptors in cell proliferation and tumour
      invasion in broncho-pulmonary carcinomas.
AB  - OBJECTIVES: Nicotine and its associated nicotinic acetylcholine receptors
      (nAChRs) are believed to be involved in the progression of lung carcinomas. This
      study aimed at examining the localization of nAChRs in human lung tumours and, by
      using primary cultures of tumour cells derived from these tumours, determining
      the nAChR roles in cell proliferation and tumour invasion. MATERIALS AND METHODS:
      Immunohistochemistry was used to assess nAChR expression in non-small cell lung
      carcinomas (NSCLC). Primary cultures of tumour cells were established from NSCLC
      tissue samples and the effects of nicotine and nAChR antagonists on cell
      proliferation and invasion were assessed. RESULTS: alpha5, alpha7, beta2 and
      beta4 nAChR subunits were expressed in all adenocarcinomas (AC) and squamous cell
      carcinomas (SCC) tissue samples. In AC, all subunits were identified in glandular
      structures. In SCC, alpha5, beta2 and beta4 subunits were essentially identified
      in tumour cells at invasive fronts, whereas alpha7 subunit was mainly present in
      the most differentiated tumour cells and less frequently at invasive fronts. In
      AC and SCC, there was an inverse distribution of cell proliferation marker Ki-67
      and alpha7 nAChR. Both alpha7 nAChR and heteromeric nAChRs positively regulated
      in vitro tumour invasion in NSCLC. Heteromeric nAChRs had a limited activity in
      regulating tumour cell proliferation in vitro. In contrast, alpha7 nAChR was a
      repressor of proliferation in tumour cells isolated from well differentiated
      NSCLC but mediated the pro-proliferative activity of nicotine in cells isolated
      from poorly differentiated NSCLC. CONCLUSION: alpha7 nAChR and heteromeric
      alpha5*beta2*beta4* nAChRs play a role in ex vivo tumour progression by
      stimulating invasion and, depending on the differentiation status of the tumour,
      by regulating proliferation. Our results suggest that the use of alpha7 nAChR
      antagonists to prevent lung cancer progression should be restricted to poorly
      differentiated tumours.

PMID- 25601487
TI  - Maintenance chemotherapy in advanced NSCLC: a population-based assessment of
      eligibility.
AB  - BACKGROUND: Maintenance chemotherapy has been incorporated into treatment
      paradigms for advanced NSCLC. Eligibility criteria include stable disease/partial
      response and PS 0-1 after a first line platinum doublet. In practice, maintenance
      can be difficult to deliver due to patient factors and preferences. We propose to
      examine the proportion of patients eligible for maintenance and factors
      associated with the delivery of subsequent lines of chemotherapy. METHODS: The BC
      Cancer Agency provides care to a population of 4.5 million. A retrospective
      review was conducted of all referred Stage IIIB/IV patients in 2009 who received
      first line systemic therapy. Baseline characteristics, PS and response after
      first line and subsequent systemic therapy details were recorded. Patients were
      deemed potentially maintenance eligible or not based on clinical trial criteria;
      however maintenance therapy was not delivered to these patients as it was not yet
      available. RESULTS: 330 patients were identified; 98 were potentially maintenance
      eligible. The reason for maintenance ineligibility in n = 232; no upfront doublet
      (n = 41), PS >= 2 (n = 38), progressive disease (PD) (n = 53), PS >= 2 and PD (n
      = 62), PS >= 2 and unknown response (n = 35), PD and unknown PS (n = 3). Further
      chemotherapy (2nd line or beyond) was administered in maintenance eligible 68% vs
      ineligible 56%. Reasons for no further chemotherapy were predominantly decline in
      PS and brain metastasis. Median OS: 7 m for 1st line only versus 16.8m for >= 2
      nd line (p < 0.001). CONCLUSIONS: In our population based study, 30% of advanced
      NSCLC patients were eligible to receive maintenance chemotherapy based on the
      clinical trial criteria. Despite a good initial PS and disease control only 68%
      of maintenance eligible patients received subsequent therapy. A clear survival
      benefit was seen with >= 2 nd line treatment. Maintenance therapy or initiation
      of early second line therapy should be considered for advanced NSCLC patients to
      improve survival outcomes.

PMID- 25601488
TI  - Identification of atypical ATRNL1 insertion to EML4-ALK fusion gene in NSCLC.
AB  - We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man
      was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR
      mutations were detected, and therefore the ALK rearrangement was evaluated using
      immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the
      reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a
      positive result and, therefore, the patient was treated with crizotinib with a
      good therapeutic response. However, a detailed RT-PCR analysis and sequencing
      revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into
      the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests
      that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. This
      case shows great EML4-ALK heterogeneity and also that basic detection methods
      (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full
      specification seems to be important for an effective TKI indication, and
      sequencing ALK variants might contribute to optimized patient selection.

PMID- 25601489
TI  - Risk of device malfunction in cancer patients with implantable cardiac device
      undergoing radiotherapy: a population-based cohort study.
AB  - BACKGROUND: Pacemakers (PMs) and implantable cardioverter defibrillators (ICDs)
      may develop malfunction during external beam radiotherapy (RT). We aimed to
      describe clinical practice in PM/ICD patients undergoing RT and to assess the
      rate and predictors of device malfunctions. METHODS: We reviewed medical records
      of all PM/ICD patients undergoing RT at four centers in Western Denmark during
      2003-2012. Logistic regression was applied to identify predictors of PM/ICD
      malfunctions. RESULTS: Five hundred sixty patients were included. The annual rate
      of RT courses in PM/ICD patients increased by 199% from 1.45 treatments per
      100,000 person-years in 2003 to 4.33 in 2012. Safety measures included
      supplementary evaluations of PM/ICD (38.3%), reprogramming (1.5%), relocation of
      the device (3.5%), and application of a magnet to the ICD during RT (10.8%). At
      device evaluations after the RT (n = 453), malfunctions were detected in 10
      (2.5%) PMs and four (6.8%) ICDs. Electrical resets constituted 11 (78.6%) of the
      malfunctions, and no failures were life-threatening or warranted PM/ICD removal.
      Factors associated with device malfunctions in logistic regression analysis were
      beam energy >=15 MV (odds ratio [OR] 5.73; 95% confidence interval [CI], 1.58
      20.76) and location of tumor below the diaphragm (OR 4.31; 95% CI, 1.42-13.12).
      However, the effect of tumor location declined (OR 2.27; 95% CI, 0.65-7.95) after
      adjustment for beam energy. CONCLUSIONS: Although the rate of RT in PM/ICD
      patients is increasing, the damaging effects of RT on the devices seem to be
      usually transient. Our data suggest that high beam energy plays the pivotal role
      in inducing impairments in these devices.

PMID- 25601491
TI  - A novel quantitative model of cell cycle progression based on cyclin-dependent
      kinases activity and population balances.
AB  - Cell cycle regulates proliferative cell capacity under normal or pathologic
      conditions, and in general it governs all in vivo/in vitro cell growth and
      proliferation processes. Mathematical simulation by means of reliable and
      predictive models represents an important tool to interpret experiment results,
      to facilitate the definition of the optimal operating conditions for in vitro
      cultivation, or to predict the effect of a specific drug in normal/pathologic
      mammalian cells. Along these lines, a novel model of cell cycle progression is
      proposed in this work. Specifically, it is based on a population balance (PB)
      approach that allows one to quantitatively describe cell cycle progression
      through the different phases experienced by each cell of the entire population
      during its own life. The transition between two consecutive cell cycle phases is
      simulated by taking advantage of the biochemical kinetic model developed by
      Gerard and Goldbeter (2009) which involves cyclin-dependent kinases (CDKs) whose
      regulation is achieved through a variety of mechanisms that include association
      with cyclins and protein inhibitors, phosphorylation-dephosphorylation, and
      cyclin synthesis or degradation. This biochemical model properly describes the
      entire cell cycle of mammalian cells by maintaining a sufficient level of detail
      useful to identify check point for transition and to estimate phase duration
      required by PB. Specific examples are discussed to illustrate the ability of the
      proposed model to simulate the effect of drugs for in vitro trials of interest in
      oncology, regenerative medicine and tissue engineering. 

PMID- 25601492
TI  - Mapping the caregiving process in paediatric asthma: Parental burden, acceptance
      and denial coping strategies and quality of life.
AB  - Based on a multidimensional model of the caregiving process, the main goal of
      this study was to examine the direct and indirect links, via acceptance and
      denial coping, between the caregiving burden and the quality of life (QoL) in
      parents of children with asthma. The sample was composed of 182 parents of a
      child/adolescent between 8 and 18 years of age with a clinical diagnosis of
      asthma. Data were obtained via self-report questionnaires assessing the
      caregiving burden, acceptance and denial coping strategies and QoL. Results from
      structural equation modelling indicated a good fit for the mediation model, which
      explained 30% of the variability of the parents' QoL. Higher levels of caregiving
      burden were negatively and indirectly associated with the parents' QoL, via less
      use of acceptance and greater use of denial coping strategies. Multigroup
      analyses ascertained the invariance of these links across the children's asthma
      severity, age and socio-economic groups. These findings emphasise acceptance and
      denial as important coping mechanisms in the caregiving process. Thus, broad
      spectrum family-centred interventions in paediatric asthma settings can target
      the development of the parents' coping tendencies characterised by greater
      acceptance and less denial as a way of reappraising caregiving demands as less
      burdensome and improving their QoL. 

PMID- 25601490
TI  - Effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1
      and cysteine/glutamate exchanger as well as ethanol drinking behavior in male,
      alcohol-preferring rats.
AB  - Alcohol consumption is largely associated with alterations in the extracellular
      glutamate concentrations in several brain reward regions. We recently showed that
      glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to
      ethanol for 5 weeks in alcohol-preferring (P) rats and that upregulation of the
      GLT-1 levels in nucleus accumbens and prefrontal cortex results, in part, in
      attenuating ethanol consumption. Cystine glutamate antiporter (xCT) is also
      downregulated after chronic ethanol exposure in P rats, and its upregulation
      could be valuable in attenuating ethanol drinking. This study examines the effect
      of a synthetic compound, (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on
      ethanol drinking and expressions of GLT-1 and xCT in the amygdala and the
      hippocampus of P rats. P rats were exposed to continuous free-choice access to
      water, 15% and 30% ethanol, and food for 5 weeks, after which they received
      treatments of MS-153 or vehicle for 5 days. The results show that MS-153
      treatment significantly reduces ethanol consumption. It was revealed that GLT-1
      and xCT expressions were downregulated in both the amygdala and the hippocampus
      of ethanol-vehicle-treated rats (ethanol-vehicle group) compared with water
      control animals. MS-153 treatment upregulated GLT-1 and xCT expressions in these
      brain regions. These findings demonstrate an important role for MS-153 in these
      glutamate transporters for the attenuation of ethanol-drinking behavior.

PMID- 25601493
TI  - Light induced modulation of charge transport phenomena across the bistability
      region in [Fe(Htrz)2(trz)](BF4) spin crossover micro-rods.
AB  - We studied the effect of light irradiation on the electrical conductance of micro
      rods of the spin crossover [Fe(Htrz)2(trz)](BF4) network, organized between
      interdigitated gold electrodes. By irradiating the sample with different
      wavelengths (between 295 and 655 nm) either in air or under a nitrogen atmosphere
      we observed both a reversible and an irreversible change of the current flowing
      in the device. The reversible process consists of an abrupt decrease of the
      current intensity (ca. 10-50%) upon light irradiation, while the irreversible
      process is characterized by a slow, but continuous increase in time of the
      current, which persists also in the dark. These photo-induced processes were only
      detected in the high conductance low-spin (LS) state of the complex. On switching
      the rods to the high spin (HS) state the conductance decreases two orders of
      magnitude (at the same temperature) and - as a consequence - the photo-effect
      vanishes. 

PMID- 25601494
TI  - Structure and properties of orthoborate glasses in the Eu2O3-(Sr,Eu)O-B2O3
      quaternary.
AB  - The structure and properties of melt-quenched glasses and partially crystallized
      samples from the borate series (1-2x)Eu2O3-x((Eu,Sr)O-B2O3) were investigated in
      the supermodified regime of x < 0.5, using Raman, infrared (IR), electron spin
      resonance (ESR), and UV-vis absorption and fluorescence spectroscopic techniques.
      ESR and optical spectroscopy showed that, despite the strongly reducing synthesis
      conditions, the Eu(2+)/Eu(3+) equilibrium remained shifted to the side of
      trivalent Eu(3+). Stable and transparent overmodified borate glasses were
      produced for compositions with x >= 0.36. Higher europium oxide concentrations
      resulted in precipitation of crystalline Eu2Sr3(BO3)4 and EuBO3 phases, as traced
      by X-ray diffraction. Raman and IR spectroscopy showed that the metaborate
      configuration which is present at x = 0.46 transforms gradually, with increasing
      Eu2O3 levels, into orthoborate [BO3](3-) triangular units. At higher europium
      oxide content (x <= 0.36), the presence of Eu(3+) supports the formation of
      orthoborate [BO2O2](3-) tetrahedral species. These units organize into [B3O9](9-)
      rings, which exist in equilibrium with [BO3](3-) triangles. As a consequence,
      distinct variations can be observed also in the macroscopic properties such as
      density, glass transition temperature, refractive index, optical basicity, and
      oxygen polarizability. This observation confirms previous findings on manganese
      strontium borates with high modification levels. 

PMID- 25601495
TI  - Lysophosphatidylcholine exacerbates Leishmania major-dendritic cell infection
      through interleukin-10 and a burst in arginase1 and indoleamine 2,3-dioxygenase
      activities.
AB  - Leishmania major is an obligate intracellular parasite hosted by phagocytes,
      including dendritic cells (DCs). Lysophosphatidylcholine (LPC) a pro-oxidant by
      product of phospholipase A2 activity can modulate the maturation and function of
      DCs. However, little is known about its role in L. major infection. This study
      examined the effects of LPC and lipopolysaccharide (LPS) in BALB/c mouse-derived
      DC infection by L. major promastigotes, in vitro. Our results showed early
      divergent effects of LPS and LPC, which lasted up to 24h. In contrast to LPS, LPC
      worsened DC infection by reversing the immune balance IL-10 vs. TNF-alpha and IL
      6, and inducing a sharp down regulation of CD40 and iNOsynthase activity. In
      addition, LPC potentiated xanthine oxidase stress, the production of kynurenine
      by indoleamine 2,3 dioxygenase (IDO), and arginase1 activity in the expense of
      iNOsynthase. Taken together, our results highlight some biochemical events
      bypassing the protective Th1 response. They suggest that LPC could facilitate the
      proliferation of this obligate intracellular parasite by neutralizing oxidative
      and nitrosative stresses and sustaining both IDO and arginase1 activities.

PMID- 25601497
TI  - Therapeutic effects of baicalin on monocrotaline-induced pulmonary arterial
      hypertension by inhibiting inflammatory response.
AB  - BACKGROUND: Baicalin has been shown to possess various pharmacological actions, a
      recent study revealed that baicalin can attenuate pulmonary hypertension and
      pulmonary vascular remodeling through the inhibition of pulmonary artery smooth
      muscle cell proliferation, however, the potential mechanism remains unexplored.
      In this study, we investigated the therapeutic effect of baicalin on a rat model
      of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and
      attempted to further clarify the possible mechanisms underlying the anti
      inflammatory. METHODS AND RESULTS: Our research showed that compared with MCT
      induced PAH model rats, rats administered intragrastically with 100mg/kg baicalin
      showed the following after two weeks: the right ventricular systolic pressure
      (RVSP) and the right ventricle/left ventricle plus septum (RV/LV+S) ratio were
      lower (P<0.05); the intima thickening and luminal stenosis were improved
      (P<0.05); the mRNA levels of tumor necrosis factor alpha (TNF-alpha), interleukin
      11beta (IL-1beta), IL-6, and endothelin-1 (ET-1) were obviously reduced by
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR); the
      protein expression of transforming growth factor-beta1 (TGF-beta1), intercellular
      cell adhesion molecule-1 (ICAM-1) and nuclear factor-kappaB (NF-kappaB) were
      significantly decreased (P<0.05); and the expression of inhibitor of NF-kappaB (I
      kappaB) was increased (P<0.05) through immunohistochemical and western blot.
      CONCLUSION: We studied the protective effects of baicalin against the lung and
      heart damage in experimental PAH rats; the therapeutic effects maybe through
      inhibiting vascular endothelial inflammatory response.

PMID- 25601496
TI  - Androctonus australis hector venom contributes to the interaction between
      neuropeptides and mast cells in pulmonary hyperresponsiveness.
AB  - Lung injury and respiratory distress syndrome are frequent symptoms observed in
      the most severe cases of scorpion envenomation. The uncontrolled transmigration
      of leukocyte cells into the lung interstitium and alveolar space and pulmonary
      edema may be the cause of death. Mast cells can release various inflammatory
      mediators known to be involved in the development of lung edema following
      scorpion venom injection. The present study was designed to determine the
      evidence of neurokinin 1 (NK1) receptor and the involvement of mast cell
      activation to induce pulmonary edema and to increase vascular permeability after
      Androctonus australis hector (Aah) venom administration. To this end, mast cells
      were depleted using compound 48/80 (C48/80). Furthermore, the involvement of
      tachykinin NK1 receptors expressed on mast cell membranes was elucidated by their
      blocking with an antagonist. On the other hand, the ability of Aah venom to
      increase vascular permeability and to induce edema was also assessed by measuring
      the amount of Evans blue dye (EBD) extravasation in bronchoalveolar lavage (BAL)
      fluid and in the lungs of mice. Pulmonary edema, as assessed by the levels of EBD
      extravasation, was completely inhibited in compound 48/80-treated animals.
      Depletion by stimuli non-immunological C48/80 component markedly reduced induced
      inflammatory response following the venom administration. The mast cells seem to
      play an important role in the development of lung injury and the increase of
      vascular permeability in mice following the subcutaneous administration of Aah
      scorpion venom through the NK1 receptor. 

PMID- 25601498
TI  - Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis
      through modulating oxidative stress and suppressing nuclear factor-kappa B
      pathway.
AB  - It has been demonstrated that circulating FGF21 levels are elevated in the serum
      and synovial fluid of patients with rheumatoid arthritis (RA). The aim of this
      study is to investigate efficacy of FGF21 for treatment of RA and the molecular
      mechanisms of the therapeutic effect on collagen-induced arthritis (CIA). Mice
      with CIA were subcutaneously administered with FGF21 (5, 2 or 1mg.kg(-1).d(-1)),
      IL-1beta antibody (5mg.kg(-1).d(-1)), IL-17A antibody (5mg.kg(-1).d(-1)) and
      dexamethasone (DEX) (1mg.kg(-1).d(-1)), respectively. The effects of treatment
      were determined by arthritis severity score, histological damage and cytokine
      production. The activation of NF-kappaB was analyzed by Western blotting. We also
      detected the levels of oxidative stress parameters. Our results showed that FGF21
      had beneficial effects on clinical symptom and histological lesion of CIA mice.
      Similar to antibody and DEX, FGF21 treatment alleviated the severity of arthritis
      by reducing humoral and cellular immune responses and down-regulating the
      expression of pro-inflammatory cytokines. FGF21 treatment also reduced the
      expression of TNF-alpha, IL-1beta, IL-6, IFN-gamma and MMP-3 and increased level
      of IL-10 in the spleen tissue or the plasma of CIA mice in a dose-dependent
      manner. Furthermore, FGF21 inhibited IkappaBalpha degradation and NF-kappaB p65
      nuclear translocation and induced significant changes of oxidative stress
      parameters (MDA, SOD, CAT, GSH-PX and GSH) in the plasma. FGF21 exerts
      therapeutic efficacy for RA through antioxidant reaction and inhibiting NF-kappaB
      inflammatory pathway. This study provides evidence that FGF21 may be a promising
      therapeutic agent for RA patients. 

PMID- 25601499
TI  - Geometry and respiratory-induced deformation of abdominal branch vessels and
      stents after complex endovascular aneurysm repair.
AB  - OBJECTIVE: This study quantified the geometry and respiration-induced deformation
      of abdominal branch vessels and stents after fenestrated (F-) and snorkel (Sn-)
      endovascular aneurysm repair (EVAR). METHODS: Twenty patients (80% male; mean
      age, 75.2 +/- 7.4 years; mean aneurysm diameter, 6.2 +/- 1.8 cm) underwent
      computed tomography angiography during inspiratory and expiratory breath hold
      protocols after F-EVAR (n = 11) or Sn-EVAR (n = 9). Centerlines for the aorta and
      visceral vessels were extracted from three-dimensional models. Branch angles were
      computed relative to the orthogonal plane at the branch ostia, and end-stent
      angles of the left renal artery (LRA) and right renal artery (RRA) were computed
      relative to the distal stent orientation. The radius of peak curvature was
      defined by the circumscribed circle at the highest curvature. RESULTS: Sn-renal
      branches were more downward-angled than F-renal branches (P < .04). At the distal
      ends of the RRA stents, Sn-RRAs were angled greater than F-RRAs (P < .03) and had
      a smaller radius of peak curvature (P < .03). With expiration, the end-stent
      angle of Sn-LRAs increased by 4 degrees  +/- 4 degrees  (P < .02) and exhibited a
      significant reduction of radius of curvature (P < .04). The unstented celiac
      arteries were more downward-angled (P < .02, inspiration), with a smaller radius
      of curvature (P < .00001), than the unstented superior mesenteric arteries. With
      expiration, the celiac arteries angled upwards by 9 degrees  +/- 9 degrees  (P <
      .0005), which was greater than the superior mesenteric arteries (P < .03). At a
      median postoperative follow-up of 12.6 months (range, 1.0-37.1 months), branch
      vessel patency was 100%, serum creatinine levels remained stable, and one
      reintervention was required for a type III endoleak at the main body-LRA stent
      interface. CONCLUSIONS: Sn-renals were angled more inferiorly at the branch and
      more angulated at the stent end than F-renals due to stent placement strategies.
      Sn-LRAs exhibited a significant change in end-stent angle and curvature during
      respiration, a finding that may compromise long-term durability for parallel
      stent graft configurations. Further investigation is warranted to better optimize
      anatomic, patient, and branch vessel stent selection between fenestrated and
      snorkel strategies and their relationship to long-term patency.

PMID- 25601501
TI  - Role of type II endoleak in sac regression after endovascular repair of
      infrarenal abdominal aortic aneurysms.
AB  - OBJECTIVE: Endovascular repair (EVAR) of infrarenal aortic aneurysms (AAA) is
      increasingly used in patients with suitable aortic morphology conforming to
      device-specific instructions for use. Despite improvements in graft design, type
      II endoleak (EL-2) from the inferior mesenteric artery (EL-IMA) or the lumbar
      artery (EL-LA) remains the Achilles' heel of EVAR. The objective of this study
      was to evaluate the natural history of the AAA sac after EVAR. We hypothesized
      that persistent EL-2 would be associated with inferior AAA sac volume regression.
      METHODS: A retrospective analysis was performed on all nonruptured AAA treated by
      elective EVAR using Food and Drug Administration-approved endografts from January
      2005 to December 2008 in our facility. Review of medical records and preoperative
      and follow-up computed tomography angiograms at 1, 6, and 12 months was
      performed. Patients with type I, III, and IV endoleaks were excluded, as were
      those lost to all follow-up. AAA size and volume were analyzed using TeraRecon
      software (Aquarius Intuition, Foster City, Calif). Change in AAA sac volume was
      compared in patients with and without EL-2, and with an occluded vs patent IMA.
      RESULTS: The study cohort comprised 191 patients (161 men, 30 women) with a mean
      age of 74 years. The mean preoperative AAA diameter was 5.5 cm (range, 4-11 cm),
      and mean volume was 137.45 cm(3). EL-2 was present in 24% at completion of EVAR
      and in 9% at a mean follow-up of 6 months (range 4-8 months). Completion
      angiography at 1 month showed 63% of EL-2 had resolved. Those with EL-2 present
      at 1 month had statistically inferior sac regression compared with those who did
      not (23% reduction vs 2% increase at 1 year; P = .002). Preoperatively, the IMA
      was occluded by coils or was chronically occluded in 82 patients vs 109 patients
      who had a patent IMA. At the 6-month follow-up, patients with an occluded IMA had
      an EL-2 rate of 2.4% vs 14.7% in those with a patent IMA (P = .005 by t-test).
      Sac volume regression was 21.8% in those with an occluded IMA vs 13.2% in those
      with a patent IMA (P = .004 by t-test). Regression in AAA sac volume was highly
      significant in patients with occluded IMA, at 30% vs 16% at 1 year (P = .0018 by
      two-sided t-test). CONCLUSIONS: The presence of persistent EL-2 after EVAR
      results in inferior AAA sac regression. A preoperatively patent IMA is associated
      with increased rates of EL-2 and inferior AAA sac regression. Consideration
      should be given to preoperative occlusion of a patent IMA before EVAR.

PMID- 25601500
TI  - Deterministic effects after fenestrated endovascular aortic aneurysm repair.
AB  - BACKGROUND: Endovascular aortic aneurysm repairs (EVARs) with fenestrated (FEVAR)
      stent grafts are high radiation dose cases, yet no skin injuries were found
      retrospectively in our 61 cases with a mean peak skin dose (PSD) of 6.8 Gy. We
      hypothesize that skin injury is under-reported. This study examined deterministic
      effects in FEVARs after procedural changes implemented to detect skin injury.
      METHODS: All FEVARs during a 6-month period with a radiation dose of 5 Gy
      reference air kerma (RAK; National Council on Radiation Protection and
      Measurements threshold for substantial radiation dose level [SRDL]) were
      included. Patients were questioned about skin erythema, epilation, and necrosis,
      with a physical examination of the back completed daily until discharge and then
      at 2 and 4 weeks and at 3 and 6 months. PSD distributions were calculated with
      custom software using input data from fluoroscopic machine logs. These
      calculations have been validated against Gafchromic (Ashland Inc, Covington, Ky)
      film measurements. Dose was summed for the subset of patients with multiple
      procedures <=6 months of the SRDL event, consistent with the joint commission
      recommendations. RESULTS: Twenty-two patients, 21 FEVARs and one embolization,
      reached an RAK of 5 Gy. The embolization procedure was excluded from review. The
      average RAK was 7.6 +/- 2.0 Gy (range, 5.1-11.4 Gy), with a mean PSD of 4.8 +/-
      2.0 Gy (range, 2.3-10.4 Gy). Fifty-two percent of patients had multiple
      endovascular procedures <=6 months of the SRDL event. The mean RAK for this
      subset was 10.0 +/- 2.9 Gy (range, 5.5-15.1 Gy), with a mean PSD of 6.6 +/- 1.9
      Gy (range, 3.4-9.4 Gy). One patient died before the first postoperative visit. No
      radiation skin injuries were found. Putative risk factors for skin injury were
      evaluated and included smoking (32%), diabetes (14%), cytotoxic drugs (9%), and
      fair skin type (91%). No other risk factors were present (hyperthyroidism,
      collagen vascular disorders). CONCLUSIONS: Deterministic skin injuries are
      uncommon after FEVAR, even at high RAK levels, regardless of cumulative dose
      effects. This study addresses the concern of missed injuries based on the
      retrospective clinical examination findings that were published in our previous
      work. Even with more comprehensive postoperative skin examinations and patient
      questioning, the fact that no skin injuries were found suggests that radiation
      induced skin injuries are multifactorial and not solely dose dependent.

PMID- 25601502
TI  - Discussion.

PMID- 25601503
TI  - Selective shunting for carotid endarterectomy in patients with recent stroke.
AB  - OBJECTIVE: Many surgeons favor routine shunting during carotid endarterectomy
      (CEA) in patients with recent stroke who otherwise prefer selective shunt
      placement for other indications of CEA. We analyzed the results of CEA in this
      group of patients with the strategy of selective shunting. METHODS: A
      retrospective review was performed of 59 patients (group A) undergoing CEA <=8
      weeks of a stroke (2000-2014) from two midsized teaching hospitals with stroke
      certification; of these, 38 patients had CEA <=2 weeks and 21 other had CEA >2
      weeks but <8 weeks. All patients sustained a middle cerebral artery stroke with
      >=70% ipsilateral internal carotid artery stenosis. Cervical block anesthesia was
      used in 43 patients and general anesthesia in 16. During the same period, 1036
      CEAs were performed for other indications (group B). All patients in group A were
      evaluated by stroke neurologist with a National Institutes of Health stroke scale
      score of 1 to 4 in 22 patients (minor stroke) and 5 to 15 in 37 patients
      (moderate stroke). A shunt was placed if neurologic changes (contralateral motor
      weakness, aphasia, loss of consciousness) occurred with the carotid cross
      clamping or ischemic electroencephalogram changes under general anesthesia were
      observed. RESULTS: The study population consisted of 59 patients (36 males and 23
      females) in group A with mean age of 70.5 +/- 10.7 years. Carotid duplex imaging
      revealed contralateral internal carotid artery stenosis of <50% in 36 patients,
      50% to 70% in 13, 71% to 99% in 9, and occlusion in 1. Ten patients (16.9%)
      required shunt placement, which was similar to the shunt in group B (11.8% for
      remote stroke, 10.2% for focal transient ischemic attack/monocular blindness, and
      10.9% for asymptomatic carotid stenosis). Two patients in group A had
      perioperative stroke and died (3.4% stroke/mortality). There were no incidences
      of permanent cranial nerve palsy, myocardial infarction (MI), or hematoma
      requiring re-exploration in patients undergoing CEA in group A. Postoperative
      complications in group B included new neurologic deficits (postoperative stroke)
      in 16 (1.6%), MI in 2 (0.2%), permanent cranial nerve palsy in 3 (0.3%), and re
      exploration for neck hematoma in 7 (0.7%). Six patients died after CEA in group
      B, for a combined stroke/death rate of 2.0%. Seizures after CEA for a recent
      stroke occurred in three patients (5.1%) in group A and in none in group B (P <
      .002). Postoperative complications (new neurologic deficits, MI, cranial nerve
      palsy, and re-exploration for neck hematoma) were similar in both groups (P >
      .05). CONCLUSIONS: Shunt requirement during CEA for acute stroke is similar to
      other indications of CEA. Patients undergoing CEA for recent stroke had similar
      incidence of postoperative new neurologic deficit/mortality, MI, and cranial
      nerve palsy compared with other indications of CEA but had a higher incidence of
      perioperative seizures.

PMID- 25601504
TI  - Discussion.

PMID- 25601505
TI  - Isolated celiac artery dissection.
AB  - OBJECTIVE: Spontaneous celiac artery dissection is rare, and its natural history
      is not well studied. The objective of this study was to review our experience
      with the evaluation and management of this condition. METHODS: During the last 8
      years, 19 patients (14 men, five women) presented with the diagnosis of
      spontaneous celiac artery dissection. Each patient's clinical course was
      retrospectively reviewed, and patients were contacted for assessment of current
      symptoms. RESULTS: All patients had computed tomography scans documenting a
      celiac artery dissection without concomitant aortic dissection. Ages ranged from
      39 to 76 years. Seven patients presented with abdominal pain, and 12 were
      diagnosed incidentally. All patients were initially treated with observation
      because none had threatened end organs. Patients presenting with aspirin or
      clopidogrel therapy were continued on these medications, but no patients were
      prescribed any medications due to their dissection. Three patients continued to
      have abdominal pain and eventually underwent celiac artery stenting. Pain
      improved after the intervention in all three. One patient with aneurysmal
      degeneration of the celiac artery underwent surgical repair. No other patients
      required intervention. Eighteen patients had follow-up within a year of data
      collection in the clinic or over the phone. The average time from the initial
      diagnosis to follow-up for the entire cohort was 46 months. None had abdominal or
      back pain related to the celiac dissection, had lost weight, or had to change
      their eating habits. CONCLUSIONS: Celiac artery dissection can be safely managed
      initially with observation. If abdominal pain is persistent, endovascular
      stenting may stabilize or improve the pain, and surgical reconstruction can be
      done for aneurysmal degeneration or occlusion, both unusual events. Long-term
      anticoagulation does not appear necessary in these patients.

PMID- 25601506
TI  - Participation in the Vascular Quality Initiative is associated with improved
      perioperative medication use, which is associated with longer patient survival.
AB  - OBJECTIVE: Medical management (MM) with antiplatelet (AP) and statin therapy is
      recommended for most patients undergoing vascular surgery and has been advocated
      by the Vascular Quality Initiative (VQI). We analyzed the effect of VQI
      participation on perioperative (preoperative and postoperative) MM use over time
      and the effect of discharge MM on patient survival. METHODS: We studied VQI
      patients treated with MM preoperatively and at discharge from 2005 to 2014,
      including all elective carotid endarterectomy/carotid stenting (n = 28,092),
      suprainguinal/infrainguinal bypass (n = 11,362), peripheral vascular
      interventions (n = 24,476), open/endovascular abdominal aortic aneurysm repair (n
      = 13,503), and thoracic endovascular aneurysm repair (n = 702). We examined
      trends of MM use over time, as well as the effect of duration of VQI
      participation on MM use. Multivariable logistic regression analysis was performed
      to identify factors associated with MM use. In addition, the Cox proportional
      hazards model was used to identify factors associated with 5-year survival.
      RESULTS: MM with AP and statin preoperatively and postoperatively across VQI
      centers improved from 55% in 2005 to 68% in 2009, with a subsequent overall
      decline to 62% by 2014, coincident with many new centers with lower MM rates
      joining VQI in 2010. Longer center participation in VQI was associated with
      improved perioperative MM overall. This was also noted across all procedure
      types, with MM increasing from 47% to 82% for aneurysm repairs and 69% to 83% for
      carotid procedures from 1 to 12 years of participation in VQI. After
      multivariable adjustment, centers in VQI >=3 years were 30% more likely to have
      patients on MM (odds ratio, 1.3, 95% confidence interval [CI], 1.3-1.4).
      Importantly, discharge on AP and statin therapy was associated with improved 5
      year survival, compared with discharge on neither medication (82% [95% CI, 81%
      83%] vs 67% [95% CI, 62%-72%]), and an adjusted hazard ratio for death of 0.6
      (95% CI, 0.5-0.7; P < .001). Discharge on a single medication was associated with
      intermediate survival at 5 years (AP only: 77% [95% CI, 75%-79%]; statin only:
      73% [95% CI, 68%-77%]). CONCLUSIONS: These data demonstrate that MM is associated
      with improved survival after a number of vascular procedures. Importantly, VQI
      participation improves the use of MM, demonstrating that involvement in an
      organized quality effort can affect patient outcomes.

PMID- 25601507
TI  - Discussion.

PMID- 25601508
TI  - Effect of caffeic acid phenethyl ester on Prevotella intermedia
      lipopolysaccharide-induced production of proinflammatory mediators in murine
      macrophages.
AB  - BACKGROUND AND OBJECTIVE: Caffeic acid phenethyl ester (CAPE) has numerous
      potentially beneficial properties, including antioxidant, immunomodulatory and
      anti-inflammatory activities. However, the effect of CAPE on periodontal disease
      has not been studied before. This study was designed to investigate the efficacy
      of CAPE in ameliorating the production of proinflammatory mediators in
      macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a
      pathogen implicated in periodontal disease. MATERIAL AND METHODS: LPS from P.
      intermedia ATCC 25611 was isolated by using the standard hot phenol-water method.
      Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1beta
      and IL-6. We used real-time polymerase chain reaction to quantify inducible NO
      synthase, IL-1beta, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine
      signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of
      signaling proteins were assessed by immunoblot analysis. DNA-binding activities
      of NF-kappaB subunits were analyzed by using the enzyme-linked immunosorbent
      assay-based kits. RESULTS: CAPE exerted significant inhibitory effects on P.
      intermedia LPS-induced production of NO, IL-1beta and IL-6 as well as their mRNA
      expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated
      with P. intermedia LPS, and selective inhibition of HO-1 activity by tin
      protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO
      production. CAPE did not interfere with IkappaB-alpha degradation induced by P.
      intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-kappaB p65
      and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity.
      Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer
      and activator of transcription 1 and 3 phosphorylation. Besides, CAPE
      significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated
      cells. CONCLUSION: Modulation of host response by CAPE may represent an
      attractive strategy towards the treatment of periodontal disease. In vivo studies
      are required to appraise the potential of CAPE further as an immunomodulator in
      the treatment of periodontal disease.

PMID- 25601509
TI  - Covalent modification of graphene oxide with carbazole groups for laser
      protection.
AB  - In the past decades, significant effort has been invested into the research and
      development of optical limiting materials and processes in order to develop
      practical solutions for the protection from laser beams. In this study, a new
      soluble graphene oxide based material (GO-Cz) has been synthesized through the
      covalent modification of graphene oxide (GO) with a carbazole derivative (Cz).
      The formation of an amido bond between the Cz group and GO has been confirmed by
      X-ray photoelectron and Fourier transform infrared spectroscopy. At the same
      concentration, both the nonlinear extinction coefficient and the imaginary third
      order susceptibility were increased by a factor of ~6.93 at 532 nm and ~6.07 at
      1064 nm relative to those of GO, as a result of the covalent grafting of the Cz
      moieties onto the GO surface. The GO-Cz dispersions exhibit a much better optical
      limiting performance than GO and GO/Cz blends at both 532 and 1064 nm due to the
      possible intramolecular electron-transfer between the GO and Cz moieties and the
      effective combination of the different nonlinear optical mechanisms. 

PMID- 25601510
TI  - Seeing it through their eyes: a qualitative study of the pregnancy experiences of
      women with a body mass index of 30 or more.
AB  - BACKGROUND: Maternal obesity [body mass index (BMI) >= 30 kg/m(2)] is associated
      with numerous complications, but currently, little is known about the pregnancy
      experiences of these women. OBJECTIVE: To gain insight into the experience of
      pregnant women with BMI >= 30 kg/m(2), when accessing maternity services and
      attending a community lifestyle programme. DESIGN: Qualitative methodology,
      utilizing focus groups and semi-structured interviews with post-natal women who
      had an antenatal BMI >= 30 kg/m(2). The sample was obtained from a larger study.
      RESULTS: Thirty-four women participated. Three main themes were identified using
      thematic analysis. Women described disappointment with their pregnancy. In
      particular, their informational expectations were not met; some health
      professionals appeared uninterested, insensitive or unconfident. Women described
      readiness to make a lifestyle change, but this was not encouraged during routine
      care. Attending the programme began the process of behavioural change. Women's
      beliefs that small changes make a big difference led to them being spurred on by
      success; driven by a desire to improve the health of their family. DISCUSSION AND
      CONCLUSION: Pregnant women who are obese know this is the case and expect to be
      provided with information to assist them in making lifestyle changes. Health
      professionals should be aware of women's readiness for change and view pregnancy
      as an ideal time to communicate. Pregnant women with a BMI >= 30 kg/m(2) should
      contribute to health professional training, to highlight the reality of the
      maternity system journey; first-hand accounts may improve the way health
      professionals' approach these women. Lifestyle interventions should be developed
      with input from the intended target group.

PMID- 25601511
TI  - Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea: a HuGE
      review and meta-analysis.
AB  - BACKGROUND: Several epidemiological studies have been conducted to examine the
      association between leptin and leptin receptor (LEPR) gene polymorphisms and risk
      of obstructive sleep apnea (OSA). However, the results remain conflicting rather
      than conclusive. OBJECTIVE: The aim of this study was to investigate associations
      of leptin and LEPR polymorphisms and risk of OSA. METHODS: We carried out a
      search in MEDLINE, EMBASE, and Chinese National Knowledge Infrastructure (CNKI)
      databases for relevant studies. Data were extracted using a standardized form and
      pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to
      assess the strength of the association. RESULTS: Overall, no statistically
      significant association of OSA risk and polymorphisms of Gln233Arg, Lys109Arg,
      Lys656Asn, 19A/G, Pro1019Arg, and 2548G/A was found. However, in the stratified
      analysis by ethnicity, Gln233Arg polymorphism was associated with a significantly
      decreased risk of OSA in European (homozygote comparison: OR = 0.35, 95% CI =
      0.14-0.85, P = 0.02), but not for Asian population. CONCLUSIONS: Our study
      suggested that leptin and LEPR polymorphisms had no association with OSA risk in
      all examined patients, whereas there was an association between Gln233Arg
      polymorphism and OSA risk in Europeans.

PMID- 25601512
TI  - Characterization of obstructive sleep apnea in patients with insomnia across
      gender and age.
AB  - OBJECTIVES: A large number of clinical observational studies have suggested that
      women patients with obstructive sleep apnea (OSA) have a higher presence of
      insomnia symptoms compared to men with OSA. There is no study that has examined
      the effect of age and gender on the relationship between OSA and chronic insomnia
      in a large number of patients with insomnia. METHODS: We collected data on 860
      patients with chronic insomnia and included both sexes and a wide range of ages
      (mean age 43.0 +/- 12.1 (range 18-81) years, 409 men). All participants underwent
      overnight polysomnography (PSG) in a sleep medicine center. RESULTS: The
      prevalence of OSA based on three different apnea-hypopnea index (AHI) categories
      (events/h >5, >15, and >30) were 42.5, 21.8, and 8.3% in men and 19.1, 6.2, and
      1.8% in women, respectively. Across age ranges of <35, 35~<45, 45~<55, and >=55
      years, the prevalence of OSA was remarkably greater in men than in women up to 55
      years of age, but not in subjects with ages >=55 years. AHI was a significant
      risk factor for hypertension; the odds ratio of hypertension in patients with
      high AHI (>30) compared to patients in the lowest AHI category (<5) was 3.68 (95%
      confidence interval [CI], 1.47-9.21), after adjusting for all other factors.
      CONCLUSION: Similar to the gender differences reported in general population
      studies, men had a much greater OSA prevalence than women prior to 55 years of
      age, but not at ages greater than 55 years.

PMID- 25601513
TI  - Noninvasive, in vivo assessment of comedone re-formation.

PMID- 25601514
TI  - Reply to the 'Comment on "Discovery of a tetracontinuous, aqueous lyotropic
      network phase with unusual 3D-hexagonal symmetry"' by G. Schroder-Turk, M.
      Fischer and S. Hyde.
AB  - A new calculation by Fischer et al. suggests that the 3etc network phase with 3D
      hexagonal symmetry (space group #193: P63/mcm) may be a generic structure adopted
      by self-assembling soft materials, thereby broadening the context for our recent
      report of its spontaneous formation in lyotropic liquid crystals. The
      experimental observation of the 3etc phase further validates previous theoretical
      models used to predict its stability, provocatively suggesting that other
      polycontinuous network phases predicted by these methods may be discovered in the
      future. While these network phase morphologies are often mathematically described
      in terms of their underlying triply periodic minimal surfaces (TPMS), the
      numerous potential applications of these functional nanostructured soft materials
      require the development of a concise, consistent, and unambiguous nomenclature
      for their complete description. In this comment, we propose adoption of a
      nomenclature that describes each mesophase more generally in terms of the total
      number of non-intersecting domains into which three-dimensional space is
      partitioned. 

PMID- 25601515
TI  - Production methods and stabilization strategies for polymer-based nanoparticles
      and microparticles for parenteral delivery of peptides and proteins.
AB  - INTRODUCTION: Therapeutic proteins and peptides often require parenteral
      administration, which compels frequent administration and patient discomfort.
      This ultimately decreases compliance and leads to therapy failure. Biocompatible
      and biodegradable polymers offer a versatile matrix for particles suitable for
      the parenteral delivery of these biomacromolecules, with the added possibility of
      long-term controlled release. During the past decade, research on polymeric
      microparticles and nanoparticles as delivery vehicles has intensified;
      nevertheless, only few products have been commercialized. AREAS COVERED: This
      review discusses the different production techniques for microparticles and
      nanoparticles suitable for peptide and protein delivery, including examples of
      recently developed formulations. Stability of the biomacromolecules related to
      these production techniques is evaluated, as it is a critical parameter to be
      considered during product development. Additionally, several strategies to
      improve stability are described in detail, providing insight and guidance for
      further formulation development. EXPERT OPINION: In the conventionally used and
      thoroughly investigated emulsification method, stability of peptides and proteins
      is still a challenge. Emerging methods like solvent displacement, layer-by-layer
      polymer deposition, electrospraying and supercritical fluid technologies have the
      potential to improve stability of the protein and peptide. Nonetheless, these
      methods are still under development and they need critical evaluation to improve
      production efficiency before proceeding to in vivo efficacy studies. Improvement
      should be achieved by strengthening cooperation between academic research groups,
      pharmaceutical companies and regulatory authorities.

PMID- 25601516
TI  - [Unusual appearance of a copper anterior chamber foreign body].

PMID- 25601517
TI  - [Fluocinolone acetonide (ILUVIEN(r)) micro-implant for chronic diabetic macular
      edema].
AB  - Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy
      and may cause severe visual loss. In this article, we examine the pathophysiology
      of DME and review various treatment options, such as laser photocoagulation, anti
      vascular endothelial growth factor (VEGF) receptor antibodies, and steroids
      including ILUVIEN((r)), which is a new sustained-release, non biodegradable,
      injectable, intravitreal micro-implant containing fluocinolone acetonide. The
      results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies,
      conducted to evaluate the efficacy and safety of ILUVIEN((r)) in DME, are
      discussed. 

PMID- 25601518
TI  - The association between lipid parameters and obesity in university students.
AB  - BACKGROUND: Abdominal obesity is associated with high plasma triglyceride and
      with low plasma high-density lipoprotein cholesterol levels. AIM AND METHODS:
      Objective of the study was to find an association between plasma lipid and
      lipoprotein levels and anthropometric parameters in abdominal obesity in
      Slovakian university students. Lipid profile and anthropometric parameters of
      obesity were studied in a sample of 419 probands, including 137 men and 282
      women. RESULTS: Males had higher values of non-high-density lipoprotein
      cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C),
      triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) than
      females, but these differences were not significant. Females had significantly (P
      < 0.05) higher TC and HDL-C (P < 0.001) than males. In comparison, all
      anthropometric parameters in the males were significantly (P < 0.001) higher than
      in the females. A positive correlation between non-HDL-C, TG, VLDL-C and
      anthropometric parameters (BMI, WC, WHR, WHtR) was found at P < 0.001. LDL was
      positively correlated with BMI, WCF, WHtR and TC with BMI, WHtR at P < 0.001. We
      also observed a correlation between TC-WCF and LDL-WHR at P < 0.01. A negative
      correlation was found between HDL and all monitored anthropometric parameters at
      P < 0.001. On the other hand, no correlation between TC and WHR was detected.
      CONCLUSION: This study shows an association between plasma lipid and lipoprotein
      levels and anthropometric parameters in abdominal obesity in young people,
      predominantly university students.

PMID- 25601519
TI  - Transforming growth factor beta2 (TGF-beta2)-induced connective tissue growth
      factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in
      human mesangial cells.
AB  - Transforming growth factor beta2 (TGF-beta2) is well known to stimulate the
      expression of pro-fibrotic connective tissue growth factor (CTGF) in several cell
      types including human mesangial cells. The present study demonstrates that TGF
      beta2 enhances sphingosine 1-phosphate receptor 5 (S1P5) mRNA and protein
      expression in a time and concentration dependent manner. Pharmacological and
      siRNA approaches reveal that this upregulation is mediated via activation of
      classical TGF-beta downstream effectors, Smad and mitogen-activated protein
      kinases. Most notably, inhibition of Gi with pertussis toxin and downregulation
      of S1P5 by siRNA block TGF-beta2-stimulated upregulation of CTGF, demonstrating
      that Gi coupled S1P5 is necessary for TGF-beta2-triggered expression of CTGF in
      human mesangial cells. Overall, these findings indicate that TGF-beta2 dependent
      upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF
      beta. Targeting S1P5 might be an attractive novel approach to treat renal
      fibrotic diseases. 

PMID- 25601520
TI  - Transcriptome profiling of the hypothalamus during prelaying and laying periods
      in Sichuan white geese (Anser cygnoides).
AB  - The Sichuan White goose is a Chinese breed well known for the quality of its
      meat. However, reproductive performance in this goose is not ideal, and little
      information is available regarding the abundance of transcripts. To better
      understand the molecular mechanism(s) underpinning prelaying and laying periods
      in the Sichuan white goose, high-throughput RNA sequencing was performed to
      analyze the transcriptome in the hypothalamus. After sequencing and annotation,
      26,921 unigenes were obtained, with 48 transcripts up-regulated in the prelaying
      period and 180 transcripts up-regulated during the laying period. These
      transcripts were primarily related to diseases, cancers, signaling molecules and
      interactions, the nervous system and the immune system. Eight transcripts were
      selected for further analyses with quantitative reverse-transcription polymerase
      chain reaction (qRT-PCR). The qRT-PCR results were mostly consistent with those
      from the high-throughput RNA sequencing. Among these transcripts,
      serine/threonine-protein kinase (AMPK), heat shock protein 70 (HSP70) and NADH
      dehydrogenase 1 (ND1) were differentially expressed during the prelaying and
      laying periods. The results of this study provide a useful resource for future
      studies examining the hypothalamus in geese.

PMID- 25601525
TI  - Dysregulation of microRNA expression in human cervical preneoplastic and
      neoplastic lesions.
AB  - Data discussed in recent reviews demonstrated that dysregulation of microRNA
      (miRNA) expression profiles occurs during cervical carcinogenesis and
      characteristic up- or downregulation of certain miRNAs might be used as
      biomarkers. The majority of altered miRNAs, however were found to be inconsistent
      upon comparison with cancerous and normal cervical epithelia in the discussed
      studies due to several reasons. The results obtained in this present review
      suggest the need for further investigations on miRNAs on larger sample sizes in
      order to indicate sensitivity and specificity by means of well defined, "unified"
      methods. In addition, obtaining further data on the clinical course and outcome
      of patients in comparison to the dysregulation of miRNA expression profile could
      turn miRNAs into prognostic and/or progression markers. Inhibition of
      overexpressed miRNAs, as suggested by some authors, might even serve as target
      for cancer therapy.

PMID- 25601526
TI  - Intrinsic correction of system delays for radial magnetic resonance imaging.
AB  - INTRODUCTION: When using radial MR image acquisition techniques gradient or
      sampling delays due to hardware imperfections can cause mismatch between the
      expected and the actual k-space trajectory along the readout direction. To
      provide a robust and simple correction of such system delays we developed a new
      calibration method which is independent of using any reference data or applying
      sequence modifications. MATERIAL AND METHODS: Radial data obtained with 180
      degrees , 360 degrees  and golden-angle radial ordering schemes were deliberately
      shifted along the readout direction for a discrete range of gradient delays.
      Following 2D regridding, images were reconstructed and analyzed in image space
      for all applied shifts to estimate the optimal system delay. Phantom and in vivo
      measurements were performed to test the robustness of the algorithm. RESULTS:
      Using the 360 degrees  and golden-angle radial ordering schemes system delays in
      the range of 3.3MUs to 6.3MUs were estimated and corrected for several imaging
      applications and different conditions, including cardiac and real-time MRI as
      well as multiple acquisitions using different imaging parameters and slice
      orientations. When using the standard 180 degrees  radial acquisition scheme no
      automated correction was possible. With a mean computation time of 23.2+/-14.0s
      for the delay estimation computational demands were moderate allowing
      implementation of the algorithm on the image reconstruction system of any modern
      MR system. CONCLUSION: We have demonstrated that radial data acquired with a 360
      degrees  or golden-angle ordering scheme can be used for reliable intrinsic
      correction of system delays. The proposed technique enables a per-scan correction
      of system delays without the need for additional calibration data or
      modifications of the radial imaging sequence.

PMID- 25601527
TI  - Feasibility of magnetic resonance imaging (MRI) in obtaining nucleus pulposus
      (NP) water content with changing postures.
AB  - Opportunities to evaluate spinal loading in vivo are limited and a large majority
      of studies on the mechanical functions of the spine have been in vitro cadaveric
      studies and/or models based on many assumptions that are difficult to validate.
      The purpose of this study was to investigate the feasibility of magnetic
      resonance imaging (MRI) in obtaining nucleus pulposus (NP) water content
      measurements with changing postures. MRI studies were conducted on 25 healthy
      males with no history of low back pain (age 20-38). The L1 to S1 intradiscal
      levels were imaged in supine, sitting and standing postures using an upright 0.6
      Tesla magnet, where a set of H2O: D2O7 phantoms were mounted on the back of the
      subjects. A calibration curve, provided from these phantoms, was applied to the
      absolute proton density image, yielding a pixel-by-pixel map of the water content
      of the NP. The NP at all levels showed a highly significant water loss (p<0.001)
      in sitting and standing postures compared with the supine posture. A trend
      towards higher levels of water was observed at all levels in the standing posture
      relative to sitting postures, however statistically significant differences were
      found only at L4-L5 and L5-S1 levels. This study demonstrates that variations in
      water content of the NP in different postures are in agreement with those
      determined from published invasive disc pressure measurements. The result of
      study demonstrates the feasibility of using MRI to determine the water content of
      the NP with changing postures and to use these data to evaluate spinal loading in
      these postures. This measurement method of water content by quantitative MR
      imaging could become a powerful tool for both clinical and ergonomic
      applications. The proposed methodology does not require invasive pressure
      measurement techniques. 

PMID- 25601528
TI  - Sub-pixel shifted acquisitions for super-resolution proton magnetic resonance
      spectroscopy (1H MRS) mapping.
AB  - PURPOSE: (1)H MRS typical studies lead to low-resolution maps (voxels
      size>1cm(3)). The low-resolution maps may involve the presence of two or more
      different tissues in a single voxel which gives partial volume effects. Such
      insufficient spatial resolution remains an obstacle for most routine clinical
      examinations and restricts the ability in the detection of small lesions.
      MATERIALS AND METHODS: The proposed algorithm is based on the combination of
      three ideas: controlled sub-pixel shift, averaging, and initial pixel size
      reduction until the spectrum extinction because initial pixel size will determine
      the final spatial resolution. Frequency range limits are studied to determine the
      optimal window of spectral peak (WSP). This method is validated in-vitro and in
      vivo. RESULTS: The results in-vitro allowed us to consolidate the theoretical
      one. Results in-vivo are compared with the clinical protocol to demonstrate the
      increase in spatial resolution. The proposed method allowed us to reduce the
      pixel size to1/16 of its initial pixel size in total scan time (TS) of 17min 10s.
      We demonstrated that the optimal WSP is 80% of its initial value and the
      interpolation "Bilinear" has the minimum error. CONCLUSION: A novel approach is
      established for processing images and reconstructing high-resolution map from low
      resolution maps. We have presented a robust algorithm for high spatial resolution
      in-vivo (1)H MRS, and have achieved a super spatial resolution up to 0.034cm(3)
      to overcome the major technical challenges.

PMID- 25601529
TI  - Automated analysis of perfusion weighted MRI using asymmetry in vascular
      territories.
AB  - PURPOSE: To determine the feasibility of automatic vascular territory region of
      interest (ROI) construction as a method for standardized quantification of
      cerebral blood flow (CBF) images. MATERIALS AND METHODS: An algorithm for
      automatic construction of vascular territory ROIs was performed on 10 healthy
      controls and 25 patients with perfusion abnormalities identified by retrospective
      chart review. The ROIs were used to quantify perfusion asymmetry for each
      territory, and perfusion asymmetry was compared in the two cohorts and against
      blinded neuroradiologist interpretation. The algorithm was additionally applied
      to a separate cohort of 23 prospectively enrolled patients and perfusion
      asymmetry was correlated against clinical variables. RESULTS: There was
      significantly greater perfusion asymmetry in territories graded by
      neuroradiologists as hypoperfused compared to those graded as normally perfused
      (p<.05) and compared to healthy volunteers (p<.01). An ROC analysis showed that
      perfusion asymmetry was sensitive and specific for identifying hypoperfusion in
      vascular territories (84.9% sensitivity and 90.5% specificity for a threshold
      asymmetry index of .829). In the prospective cohort, perfusion asymmetry was
      correlated with initial NIH stroke scale (NIHSS) (p<.01) and length of stay
      (p<.05). CONCLUSIONS: Automatic construction of vascular territory ROIs and
      calculation of perfusion asymmetry is a feasible method for analyzing CBF images.
      Because the technique is rapid and minimizes bias, it can facilitate analysis of
      larger scale research studies.

PMID- 25601530
TI  - Detection of OXA-48-like carbapenemase genes by the Xpert(r) Carba-R test: room
      for improvement.

PMID- 25601531
TI  - Pre-treatment with probiotics prolongs survival after experimental infection by
      multidrug-resistant Pseudomonas aeruginosa in rodents: an effect on sepsis
      induced immunosuppression.
AB  - Based on several randomised clinical studies indicating benefit from oral
      probiotic intake for the prevention of hospital-acquired infections in critically
      ill patients, this study aimed to explain the mechanism of action of probiotics
      for the prevention of lethal experimental infection by multidrug-resistant (MDR)
      Pseudomonas aeruginosa. Experiments using an Escherichia coli strain susceptible
      to all antimicrobials were also conducted. C57BL/6 mice were pre-treated
      intraperitoneally with sterile water for injection or Lactobacillus plantarum.
      Survival was recorded and mice were sacrificed for measurement of apoptosis and
      tissue bacterial overgrowth and for isolation and culture of splenocytes for
      cytokine production. Experiments were repeated after pre-treatment with a
      commercial preparation of four probiotics (L. plantarum, Lactobacillus
      acidophilus, Saccharomyces boulardii and Bifidobacterium lactis;
      LactoLevure((r))). Peripheral blood mononuclear cells (PBMCs) of healthy
      volunteers were stimulated by heat-killed P. aeruginosa following pre-treatment
      with medium or probiotics. Pre-treatment with L. plantarum significantly
      prolonged survival after challenge by either MDR P. aeruginosa (66.7% vs. 31.3%;
      P=0.026) or E. coli (56.0% vs. 12.0%, P=0.003). Survival benefit was even more
      pronounced when mice were pre-treated with LactoLevure((r)). Tissue bacterial
      outgrowth and apoptosis of white blood cells and splenocytes were not altered.
      TNFalpha and IL-10 production by splenocytes of mice pre-treated with probiotic
      was increased and IFNgamma production was decreased. Pre-treatment with
      LactoLevure((r)) restored production of IL-17. Stimulation of human PBMCs after
      probiotic pre-treatment was accompanied by reduced gene expression of SOCS3. The
      results suggest that the protective effect of probiotics is mediated through
      prevention of sepsis-induced immunosuppression. 

PMID- 25601532
TI  - Risk and outcomes of complications during and after MitraClip implantation:
      Experience in 828 patients from the German TRAnscatheter mitral valve
      interventions (TRAMI) registry.
AB  - AIMS: To analyze risk and outcomes of complications during and after MitraClip
      implantation using multicenter data from the prospective German Transcatheter
      Mitral Valve Interventions (TRAMI) registry. METHODS AND RESULTS: Data of 828
      patients (mean age: 76.0 [71-81] years, 327 (40%) females) undergoing MitraClip
      implantation in Germany between 2010 and 2013 were analyzed. Most patients (85%)
      underwent elective procedures with on average implantation of 1.4 +/- 0.6 clips.
      Emergent cardiac surgery was not required; a single patient died
      intraoperatively. During the in-hospital period, complications occurred in 215
      (25.9%) patients, of which 106 (12.8%) were considered major. Major bleeding
      complications were among the most frequent major complications (7.4%), while
      rates of pericardial tamponade (1.9%) and clip-specific complications
      (embolization: 0%, partial clip detachment: 1.9%) were low. In-hospital death,
      stroke or myocardial infarction (MACCE) occurred in 2.2, 0.9, and 0% patients,
      respectively. Patients with complications appeared to be older and more
      critically ill pre-interventionally; in-hospital mortality was significantly
      higher as compared to those without procedural complications. CONCLUSIONS:
      MitraClip implantation appears to be a safe treatment option with low rates of
      MACCE and clip-specific complications. Nevertheless, MitraClip therapy is not
      without complications. Careful patient selection and improvements in preventing
      peri-procedural bleeding have the potential of reducing post-procedural
      complications and improving outcomes.

PMID- 25601534
TI  - Intraocular Lens Power Selection after Radial Keratotomy: Topography, Manual, and
      IOLMaster Keratometry Results Using Haigis Formulas.
AB  - PURPOSE: To compare final spherical equivalent (SE) refractions in patients who
      previously underwent radial keratotomy (RK) undergoing routine cataract surgery
      using keratometry (K) values from the Tomey (Topographic Modeling System [TMS];
      Tomey Corp., Phoenix, AZ) Placido topographer, manual keratometer, and IOLMaster
      (Carl Zeiss Meditec AG, Jena, Germany) keratometer using the Haigis formulas.
      DESIGN: Retrospective case series. SUBJECTS: A total of 26 RK eyes (20 patients)
      with a minimum of 3 months postoperative follow-up. METHODS: The following K
      values were evaluated: TMS topography (flattest K within first 9 rings, average
      K, minimum K), manual K, IOLMaster K. The final refractive goal was -0.50
      diopters (D) for all eyes. The Haigis formula with target refraction -0.50 D was
      used. In addition, because of observed hyperopic overcorrections, IOLMaster K
      with the Haigis formula set to -1.00 D but with a final refractive goal of -0.50
      D was also tested. The Haigis-L formula using IOLMaster K values was separately
      evaluated. MAIN OUTCOME MEASURES: Mean final SE refraction, percent final SE
      within ideal (-0.12 to -1.00 D), acceptable (0.25 to -1.50 D), or unacceptable (<
      1.50 or >0.25 D) range and within +/-0.50 D and +/-1.00 D of the intended result.
      RESULTS: Best results with minimal overcorrections were achieved with TMS
      flattest K (mean -0.68+/-0.60 D, 73% within +/-0.50 D, and 88% within +/-1.00 D
      of the surgical goal) and IOLMaster K set for target -1.00 D (mean -0.66+/-0.61
      D, 69% within +/-0.50 D, and 88% within +/-1.00 D of the surgical goal). Other
      values produced more hyperopic (manual, IOLMaster K set for target -0.50 D,
      average topography) or higher myopic (minimum topography, Haigis-L) results.
      CONCLUSIONS: For simplicity, using the IOLMaster K values combined with the
      Haigis formula set for target refraction -1.00 D produces acceptable results
      aiming for -0.50 D final SE refractions in former RK patients undergoing routine
      cataract surgery.

PMID- 25601535
TI  - Effects of intravitreal ranibizumab on retinal hard exudate in diabetic macular
      edema: findings from the RIDE and RISE phase III clinical trials.
AB  - PURPOSE: To evaluate the effect of monthly intravitreal ranibizumab on hard
      exudate (HE) area and the impact of HE on visual acuity (VA) outcomes in diabetic
      macular edema (DME) patients using data from 2 phase III clinical trials. DESIGN:
      Exploratory analyses of phase III, randomized, double-masked, sham-controlled,
      multicenter clinical trials. PARTICIPANTS: Adults with DME, baseline best
      corrected VA 20/40 to 20/320 Snellen equivalent, and central foveal thickness of
      >=275 MUm. METHODS: Between the 2 studies, 759 patients with DME were randomized
      to receive monthly 0.3 or 0.5 mg intravitreal ranibizumab (Lucentis; Genentech,
      Inc., South San Francisco, CA) or sham injections. MAIN OUTCOME MEASURES: Hard
      exudate area was assessed from color fundus stereophotographs both on an ordinal
      scale and using continuous estimates of areas within the Early Treatment Diabetic
      Retinopathy Study grid. RESULTS: Data from 739 eyes were available for analysis.
      Mean baseline HE area was similar across treatment groups, ranging from 0.65 to
      0.82 mm(2). Through month 24, the percentage of eyes without HE increased from
      20.9% to 36.3% in the sham group and from 22.1% to 61.3% and 23.6% to 62.0% in
      the ranibizumab 0.3-mg and 0.5-mg groups, respectively. Resolution of HE became
      apparent sometime after month 6 in ranibizumab-treated eyes. At baseline, there
      was no meaningful correlation between VA and presence or absence of HE. After
      baseline, there also was no consistent correlation between presence or absence of
      HE and change in VA over time. CONCLUSIONS: In this exploratory analysis, monthly
      intravitreal ranibizumab resulted in significantly greater reduction of HE area
      compared with sham (P < 0.0001). In contrast to the rapid effects of ranibizumab
      on macular edema, changes in HE area were more gradual. Contrary to prior
      expectations, the presence and area of HE did not increase as DME resolved
      (either in the ranibizumab or sham groups). Importantly, baseline VA was not
      correlated with presence of HE, nor was the therapeutic benefit of ranibizumab on
      VA affected negatively by the presence of HE. These data suggest that in the
      context of intravitreal anti-vascular endothelial growth factor therapy, the
      presence of HE is not a prognostic indicator of poor visual outcomes.

PMID- 25601536
TI  - Factors affecting visual acuity after cataract surgery in patients with retinitis
      pigmentosa.
AB  - PURPOSE: To investigate the factors affecting visual acuity after cataract
      surgery in patients with retinitis pigmentosa (RP). DESIGN: Retrospective,
      observational study. PARTICIPANTS: We retrospectively reviewed the charts of a
      consecutive series of 40 patients with RP who underwent cataract surgery.
      METHODS: The changes in preoperative and postoperative best-corrected visual
      acuity (BCVA) were measured. We investigated the relation between preoperative
      mean deviation (MD) value on the Humphrey Field Analyzer (HFA: the central 10-2
      program; Humphrey Instruments, Inc, San Leandro, CA) and final BCVA. We also
      investigated the relationship between preoperative ellipsoid zone (EZ; also
      called the inner/outer segment junction) conditions and final BCVA. In addition,
      we showed the prevalence of macular complications and capsule complications. MAIN
      OUTCOME MEASURES: The BCVA, slit-lamp biomicroscopic analysis, visual field, and
      optical coherence tomography (OCT) were obtained. RESULTS: The mean of the BCVA
      significantly improved after cataract surgery from 0.76 (range, -0.08 to 2.30) to
      0.45 (range, -0.18 to 2.00) (P < 0.005). However, final BCVA did not improve in
      30 eyes (53.6%). The preoperative MD value and the final BCVA were significantly
      correlated, and the final BCVA significantly improved in the less advanced RP
      group (MD was >=-15 decibels [dB]). The final BCVA was significantly better in
      the group in which preoperative OCT showed a normal EZ than in the groups in
      which the EZ was abnormal or not visible. Posterior capsular opacification was
      observed in 47 eyes (83.9%), and 23 eyes (41.1%) underwent YAG laser capsulotomy
      within a mean follow-up time of 3 years. CONCLUSIONS: Final BCVA in approximately
      half of the eyes improved after cataract surgery in patients with RP. The
      preoperative ophthalmic examinations that may reflect macular (or foveal)
      function, such as HFA 10-2 program and OCT, are important parameters to assess
      postoperative visual outcome.

PMID- 25601533
TI  - Multimodal characterization of proliferative diabetic retinopathy reveals
      alterations in outer retinal function and structure.
AB  - PURPOSE: To identify changes in retinal function and structure in persons with
      proliferative diabetic retinopathy (PDR), including the effects of panretinal
      photocoagulation (PRP). DESIGN: Cross-sectional study. PARTICIPANTS: Thirty
      adults who underwent PRP for PDR, 15 adults with untreated PDR, and 15 age
      matched controls. METHODS: Contrast sensitivity, frequency doubling perimetry
      (FDP), Humphrey visual fields, photostress recovery, and dark adaptation were
      assessed. Fundus photography and macular spectral-domain optical coherence
      tomography (SD OCT) were performed. To quantify retinal layer thicknesses, SD OCT
      scans were segmented semiautomatically. MAIN OUTCOME MEASURES: Visual function
      measures were compared among patients with PDR and PRP, untreated patients with
      PDR, and controls. Mean retinal layer thicknesses were compared between groups.
      Correlation analyses were performed to evaluate associations between visual
      function measures and retinal layer thicknesses. RESULTS: A significant reduction
      of FDP mean deviation (MD) was exhibited in PRP-treated patients with PDR (MD +/-
      standard deviation, -8.20+/-5.76 dB; P < 0.0001) and untreated patients (-5.48+/
      4.48 dB; P < 0.0001) relative to controls (1.07+/-2.50 dB). Reduced log contrast
      sensitivity compared with controls (1.80+/-0.14) also was observed in both PRP
      treated patients (1.42+/-0.17; P < 0.0001) and untreated patients (1.56+/-0.20; P
      = 0.001) with PDR. Compared with controls, patients treated with PRP demonstrated
      increased photostress recovery time (151.02+/-104.43 vs. 70.64+/-47.14 seconds; P
      = 0.001) and dark adaptation speed (12.80+/-5.15 vs. 9.74+/-2.56 minutes; P =
      0.022). Patients who underwent PRP had diffusely thickened nerve fiber layers (P
      = 0.024) and diffusely thinned retinal pigment epithelium (RPE) layers (P =
      0.009) versus controls. Untreated patients with PDR also had diffusely thinned
      RPE layers (P = 0.031) compared with controls. CONCLUSIONS: Patients with
      untreated PDR exhibited inner retinal dysfunction, as evidenced by reduced
      contrast sensitivity and FDP performance, accompanied by alterations in inner and
      outer retinal structure. Patients who underwent PRP had more profound changes in
      outer retinal structure and function. Distinguishing the effects of PDR and PRP
      may guide the development of restorative vision therapies for patients with
      advanced diabetic retinopathy.

PMID- 25601537
TI  - [Lactococcus lactis thyroid abscess in an immunocompetent patient].

PMID- 25601538
TI  - Effectiveness of ecallantide in treating angiotensin-converting enzyme inhibitor
      induced angioedema in the emergency department.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-AE)
      is mediated by bradykinin. There remains an unmet treatment need because these
      patients, when presenting to the emergency department (ED), do not respond to
      conventional therapies, such as antihistamines and corticosteroids. OBJECTIVE: To
      estimate the treatment effect of ecallantide, a recombinant plasma kallikrein
      inhibitor, in ED patients with ACEI-AE in whom conventional therapy fails.
      METHODS: This was a triple-blind (patient, physician, and statistician),
      randomized, controlled, phase 2 study to estimate the magnitude of safety and
      efficacy signals for designing a definitive phase 3 trial comparing conventional
      therapy with ecallantide to conventional therapy with placebo. Patients were
      enrolled from April 1, 2010, through January 31, 2013. The primary efficacy study
      end point was achieving discharge criteria from the ED within 4 hours after
      initiating study-related treatment. RESULTS: Discharge criteria from the ED was
      met in 4 hours or less for 8 (31%) of 26 patients receiving ecallantide vs 5 of
      (21%) 24 patients receiving placebo (difference in proportions, 10%; 95%
      confidence interval, -14% to 34%). Ecallantide was well tolerated in both groups.
      CONCLUSION: The results from this preliminary study reveal that ecallantide is
      safe to use and may increase the proportion of patients who meet early discharge
      criteria by approximately10%. A larger phase 3 study is necessary to confirm the
      efficacy and evaluate the cost-effectiveness of ecallantide use for ACEI-AE in
      the ED setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01036659.

PMID- 25601539
TI  - Allergy after ingestion of bee-gathered pollen: influence of botanical origins.

PMID- 25601540
TI  - Accuracy of Doppler echocardiographic estimates of pulmonary artery pressures in
      a canine model of pulmonary hypertension.
AB  - OBJECTIVES: To compare noninvasive estimates of pulmonary artery pressure (PAP)
      obtained via echocardiography (ECHO) to invasive measurements of PAP obtained
      during right heart catheterization (RHC) across a range of PAP. To examine the
      accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP
      measured by RHC (RAPRHC), and determine if adding RAPECHO improves the accuracy
      of noninvasive PAP estimations. ANIMALS: 14 healthy female beagle dogs. METHODS:
      Comparison of ECHO and RHC measures of PAP, both at normal PAP and increased PAP
      generated by microbead embolization. RESULTS: Noninvasive estimates of PAP were
      moderately but significantly correlated (r of 0.68-0.78; p < 0.0006) with
      invasive measurements of PAP. Wide variance was noted for all estimations, with
      increased variance at higher PAP. The addition of RAPECHO improved correlation
      and bias in all cases. RAPRHC was significantly correlated with RAPECHO (r =
      0.38; p = 0.04) as estimated by the ellipse area method. Median RAPRHC was
      significantly different between 3 subjective assessments of right atrial size (p
      = 0.037). CONCLUSIONS: Spectral Doppler assessments of tricuspid and pulmonic
      regurgitation are imperfect methods for predicting PAP as measured by
      catheterization despite an overall moderate correlation between invasive and
      noninvasive values. Noninvasive measurements may be better utilized as part of a
      comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated
      based on subjective assessment of RA size. Including estimated RAPECHO in
      estimates of PAP improves the correlation and relatedness between noninvasive and
      invasive measures of PAP, but notable variability in accuracy of estimations
      persists.

PMID- 25601543
TI  - Intermediate analysis of a phase II trial assessing gemcitabine and cisplatin in
      locoregional or metastatic penile squamous cell carcinoma.
AB  - OBJECTIVE: To perform a phase II study evaluating a combination of gemcitabine
      and cisplatin in a population of patients with squamous cell carcinoma (SCC) of
      the penis and unresected locoregional lymph nodes and/or distant metastases, who
      had a poor prognosis with no standard of chemotherapy. PATIENTS AND METHODS:
      Eligible patients had histologically confirmed SCC of the penis with unresected
      locoregional lymph nodes and/or distant metastases, at initial diagnosis or at
      relapse, and measurable disease as defined by Response Evaluation Criteria in
      Solid Tumors (RECIST) criteria. Patients were treated with a combination of
      gemcitabine 1250 mg/m(2) on day 1 over 30 min and cisplatin 50 mg/m(2) on day 1
      over 1 h, every 2 weeks. The primary endpoint was the objective response rate;
      secondary endpoints were time to progression (TTP) and overall survival (OS).
      RESULTS: In all, 25 patients were included in the first phase of the study
      between February 2004 and January 2010 and received a median of five cycles. For
      the intent-to-treat population, two patients (95% confidence interval [CI] 0.98
      26.0) presented an objective response and 13 patients (52%) had stable disease
      (95% CI 35.5-76.8). The median TTP was at 5.48 months (95% CI 2.40-11.73). After
      a median follow-up of 26.97 months (95% CI 17.77, not reached), nine patients
      were still alive. The median OS and 2-year OS rate were respectively estimated at
      14.98 months (95% CI 9.76-32.9) and 39.32% (95% CI 19.15-59.03). Eleven patients
      had a serious adverse event (44%), 24% being relied to chemotherapy. CONCLUSION:
      Every 2 weeks' administration of the combination of gemcitabine and cisplatin
      showed non-significant responses in patients with unresected locoregional or
      metastatic penile SCC. Despite manageable side-effects, this combination cannot
      be recommended as a standard of care, due to disappointing response rates seen in
      this negative study. Further regimens should be explored to improve the OS of
      these patients with poor prognosis.

PMID- 25601541
TI  - Targeting T cell metabolism for therapy.
AB  - In the past several years a wealth of evidence has emerged illustrating how
      metabolism supports many aspects of T cell biology, as well as how metabolic
      changes drive T cell differentiation and fate. We outline developing principles
      in the regulation of T cell metabolism, and discuss how these processes are
      affected in settings of inflammation and cancer. In this context we discuss how
      metabolic pathways might be manipulated for the treatment of human disease,
      including how metabolism may be targeted to prevent T cell dysfunction in
      inhospitable microenvironments, to generate more effective adoptive cellular
      immunotherapies in cancer, and to direct T cell differentiation and function
      towards non-pathogenic phenotypes in settings of autoimmunity. 

PMID- 25601545
TI  - Activation of dorsal raphe serotonergic neurons promotes waiting but is not
      reinforcing.
AB  - BACKGROUND: The central neuromodulator serotonin (5-HT) has been implicated in a
      wide range of behaviors and affective disorders, but the principles underlying
      its function remain elusive. One influential line of research has implicated 5-HT
      in response inhibition and impulse control. Another has suggested a role in
      affective processing. However, whether and how these effects relate to each other
      is still unclear. RESULTS: Here, we report that optogenetic activation of 5-HT
      neurons in the dorsal raphe nucleus (DRN) produces a dose-dependent increase in
      mice's ability to withhold premature responding in a task that requires them to
      wait several seconds for a randomly delayed tone. The 5-HT effect had a rapid
      onset and was maintained throughout the stimulation period. In addition, movement
      speed was slowed, but photostimulation did not affect reaction time or time spent
      at the reward port. Using similar photostimulation protocols in place preference
      and value-based choice tests, we found no evidence of either appetitive or
      aversive effects of DRN 5-HT neuron activation. CONCLUSIONS: These results
      provide strong evidence that the efficacy of DRN 5-HT neurons in promoting
      waiting for delayed reward is independent of appetitive or aversive effects and
      support the importance of 5-HT in behavioral persistence and impulse control.

PMID- 25601544
TI  - NDR functions as a physiological YAP1 kinase in the intestinal epithelium.
AB  - BACKGROUND: Phosphorylation of the transcriptional coactivator YAP1 is a key
      event in defining Hippo signaling outputs. Previous studies demonstrated that
      phosphorylation of YAP1 at serine 127 (S127) sequesters YAP1 in the cytoplasm and
      consequently inhibits YAP1 transcriptional activity. Mammalian tissue-culture
      experiments suggest that downstream of MST1/2 signaling, LATS1/2 function as YAP1
      S127 kinases. However, studies of Mst1/2 knockout mouse models revealed that the
      identity of the physiological YAP1-S127 kinase(s) in certain tissues, such as the
      intestine, remains unknown. RESULTS: We show that mammalian NDR1/2 kinases
      phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in
      tissue-cultured cells. By studying NDR1/2-deficient mice, we demonstrate the in
      vivo relevance of NDR1/2-mediated regulation of YAP1. Specifically, upon loss of
      NDR1/2 in the intestinal epithelium, endogenous S127 phosphorylation is decreased
      whereas total YAP1 levels are increased. Significantly, ablation of NDR1/2 from
      the intestinal epithelium renders mice exquisitely sensitive to chemically
      induced colon carcinogenesis. Analysis of human colon cancer samples further
      revealed that NDR2 and YAP1 protein expression are inversely correlated in the
      majority of samples with high YAP1 expression. Collectively, we report NDR1/2 as
      physiological YAP1-S127 kinases that might function as tumor suppressors upstream
      of YAP1 in human colorectal cancer. CONCLUSIONS: We establish mammalian NDR1/2 as
      bona fide kinases that target YAP1 on S127 in vitro and in vivo. Our findings
      therefore have important implications for a broad range of research efforts aimed
      at decoding and eventually manipulating YAP1 biology in cancer settings,
      regenerative medicine, and possibly also noncancer human diseases.

PMID- 25601546
TI  - Evidence for geomagnetic imprinting and magnetic navigation in the natal homing
      of sea turtles.
AB  - Natal homing is a pattern of behavior in which animals migrate away from their
      geographic area of origin and then return to reproduce in the same location where
      they began life [1-3]. Although diverse long-distance migrants accomplish natal
      homing [1-8], little is known about how they do so. The enigma is epitomized by
      loggerhead sea turtles (Caretta caretta), which leave their home beaches as
      hatchlings and migrate across entire ocean basins before returning to nest in the
      same coastal area where they originated [9, 10]. One hypothesis is that turtles
      imprint on the unique geomagnetic signature of their natal area and use this
      information to return [1]. Because Earth's field changes over time, geomagnetic
      imprinting should cause turtles to change their nesting locations as magnetic
      signatures drift slightly along coastlines. To investigate, we analyzed a 19-year
      database of loggerhead nesting sites in the largest sea turtle rookery in North
      America. Here we report a strong association between the spatial distribution of
      turtle nests and subtle changes in Earth's magnetic field. Nesting density
      increased significantly in coastal areas where magnetic signatures of adjacent
      beach locations converged over time, whereas nesting density decreased in places
      where magnetic signatures diverged. These findings confirm central predictions of
      the geomagnetic imprinting hypothesis and provide strong evidence that such
      imprinting plays an important role in natal homing in sea turtles. The results
      give credence to initial reports of geomagnetic imprinting in salmon [11, 12] and
      suggest that similar mechanisms might underlie long-distance natal homing in
      diverse animals.

PMID- 25601547
TI  - Reducing social stress elicits emotional contagion of pain in mouse and human
      strangers.
AB  - Empathy for another's physical pain has been demonstrated in humans [1] and mice
      [2]; in both species, empathy is stronger between familiars. Stress levels in
      stranger dyads are higher than in cagemate dyads or isolated mice [2, 3],
      suggesting that stress might be responsible for the absence of empathy for the
      pain of strangers. We show here that blockade of glucocorticoid synthesis or
      receptors for adrenal stress hormones elicits the expression of emotional
      contagion (a form of empathy) in strangers of both species. Mice and
      undergraduates were tested for sensitivity to noxious stimulation alone and/or
      together (dyads). In familiar, but not stranger, pairs, dyadic testing was
      associated with increased pain behaviors or ratings compared to isolated testing.
      Pharmacological blockade of glucocorticoid synthesis or glucocorticoid and
      mineralocorticoid receptors enabled the expression of emotional contagion of pain
      in mouse and human stranger dyads, as did a shared gaming experience (the video
      game Rock Band) in human strangers. Our results demonstrate that emotional
      contagion is prevented, in an evolutionarily conserved manner, by the stress of a
      social interaction with an unfamiliar conspecific and can be evoked by blocking
      the endocrine stress response.

PMID- 25601548
TI  - A unique apposition compound eye in the mesopelagic hyperiid amphipod
      Paraphronima gracilis.
AB  - The mesopelagic habitat is a vast space that lacks physical landmarks and is
      structured by depth, light penetration, and horizontal currents. Solar
      illumination is visible in the upper 1,000 m of the ocean, becoming dimmer and
      spectrally filtered with depth-generating a nearly monochromatic blue light
      field. The struggle to perceive dim downwelling light and bioluminescent sources
      and the need to remain unseen generate contrasting selective pressures on the
      eyes of mesopelagic inhabitants. Hyperiid amphipods are cosmopolitan members of
      the mesopelagic fauna with at least ten different eye configurations across the
      family-ranging from absent eyes in deep-living species to four enlarged eyes in
      mesopelagic individuals. The hyperiid amphipod Paraphronima gracilis has a pair
      of bi-lobed apposition compound eyes, each with a large upward-looking portion
      and a small lateral-looking portion. The most unusual feature of the P. gracilis
      eye is that its upward-looking portion is resolved into a discontinuous retina
      with 12 distinct groups, each serving one transverse row of continuously spaced
      facets. On the basis of eye morphology, we estimated spatial acuity (2.5 degrees 
      +/- 0.11 degrees , SEM; n = 25) and optical sensitivity (30 +/- 3.4 MUm(2) ? sr,
      SEM; n = 25). Microspectrophotometry showed that spectral sensitivity of the eye
      peaked at 516 nm (+/-3.9 nm, SEM; n = 6), significantly offset from the peak of
      downwelling irradiance in the mesopelagic realm (480 nm). Modeling of spatial
      summation within the linear retinal groups showed that it boosts sensitivity with
      less cost to spatial acuity than more typical configurations.

PMID- 25601549
TI  - Continuous updating of visuospatial memory in superior colliculus during slow eye
      movements.
AB  - BACKGROUND: Primates can remember and spatially update the visual direction of
      previously viewed objects during various types of self-motion. It is known that
      the brain "remaps" visual memory traces relative to gaze just before and after,
      but not during, discrete gaze shifts called saccades. However, it is not known
      how visual memory is updated during slow, continuous motion of the eyes. RESULTS:
      Here, we recorded the midbrain superior colliculus (SC) of two rhesus monkeys
      that were trained to spatially update the location of a saccade target across an
      intervening smooth pursuit (SP) eye movement. Saccade target location was varied
      across trials so that it passed through the neuron's receptive field at different
      points of the SP trajectory. Nearly all (99% of) visual responsive neurons, but
      no motor neurons, showed a transient memory response that continuously updated
      the saccade goal during SP. These responses were gaze centered (i.e., shifting
      across the SC's retinotopic map in opposition to gaze). Furthermore, this
      response was strongly enhanced by attention and/or saccade target selection.
      CONCLUSIONS: This is the first demonstration of continuous updating of visual
      memory responses during eye motion. We expect that this would generalize to other
      visuomotor structures when gaze shifts in a continuous, unpredictable fashion.

PMID- 25601550
TI  - RGS proteins and septins cooperate to promote chemotropism by regulating polar
      cap mobility.
AB  - BACKGROUND: Septins are well known to form a boundary between mother and daughter
      cells in mitosis, but their role in other morphogenic states is poorly
      understood. RESULTS: Using microfluidics and live-cell microscopy, coupled with
      new computational methods for image analysis, we investigated septin function
      during pheromone-dependent chemotropic growth in yeast. We show that septins
      colocalize with the regulator of G protein signaling (RGS) Sst2, a GTPase
      activating protein that dampens pheromone receptor signaling. We show further
      that the septin structure surrounds the polar cap, ensuring that cell growth is
      directed toward the source of pheromone. When RGS activity is abrogated, septins
      are partially disorganized. Under these circumstances, the polar cap travels
      toward septin structures and away from sites of exocytosis, resulting in a loss
      of gradient tracking. CONCLUSIONS: Septin organization is dependent on RGS
      protein activity. When assembled correctly, septins promote turning of the polar
      cap and proper tracking of a pheromone gradient.

PMID- 25601552
TI  - alpha-SMA-Cre-mediated excision of PDK1 reveals an essential role of PDK1 in
      regulating morphology of cardiomyocyte and tumor progression in tissue
      microenvironment.
AB  - The phosphoinositide-3 kinase (PI3K) - phosphoinositide-dependent protein kinase
      1 (PDK1)-Akt/protein kinase B (PKB) cascade plays a critical role in
      cardiovascular development and tumor genesis. But the role of PDK1 in the
      microenvironment of heart and tumor remains unknown. To clarify the effects of
      PDK1 on tissue microenvironment in vivo, here, we created alpha-SMA-Cre-mediated
      excision of PDK1 mice. And the mice were injected subcutaneously with Lewis lung
      carcinoma (LLC) cells. We found PDK1-deficient mice had post-natal praecox
      dilated cardiomyopathy, decelerated tumor growth and severe tumor metastasis.
      Histopathological analysis revealed abnormality of vascular microenvironment in
      heart and primary tumor. In conclusion, PDK1 plays a pivotal role in regulating
      cardiac function and tumor metastasis by interfering with microenvironment. 

PMID- 25601551
TI  - Preservation of vision by the pulvinar following early-life primary visual cortex
      lesions.
AB  - BACKGROUND: Conscious vision is believed to depend upon an intact primary visual
      cortex (V1), although injury in early life is often accompanied by the
      preservation of visual capacity, unlike in adulthood. The middle temporal area
      (MT) receives input from the retinorecipient koniocellular layers of the lateral
      geniculate nucleus (LGN) and the more recently described medial subdivision of
      the inferior pulvinar (PIm) of the thalamus, pathways that potentially contribute
      to preservation of vision after early damage to V1. RESULTS: We examined the
      potential of these pathways to the long-term preservation of vision after
      permanent lesions of primate V1 in early and adult life by using a combination of
      neural tracing and diffusion MRI. We show that early-life V1 lesions lead to less
      pruning of the retina-pulvinar-MT pathway than is observed in control or adult
      lesion animals. CONCLUSIONS: These findings suggest that sustained visual input
      through the pulvinar to MT following a lesion of V1 in early life has the
      capacity to afford improved visual outcomes.

PMID- 25601553
TI  - Colonisation of the gut by bifidobacteria is much more common in vaginal
      deliveries than Caesarean sections.

PMID- 25601554
TI  - Magnetization reversal using excitation of collective modes in nanodot matrices.
AB  - The large arrays of magnetic dots are the building blocks of magnonic crystals
      and the emerging bit patterned media for future recording technology. In order to
      fully utilize the functionalities of high density magnetic nanodots, a method for
      the selective reversal of a single nanodot in a matrix of dots is desired. We
      have proposed a method for magnetization reversal of a single nanodot with
      microwave excitation in a matrix of magneto-statically interacting dots. The
      method is based on the excitation of collective modes and the spatial anomaly in
      the microwave power absorption. We perform numerical simulations to demonstrate
      the possibility of switching a single dot from any initial state of a 3 by 3
      matrix of dots, and develop a theoretical model for the phenomena. We discuss the
      applicability of the proposed method for introducing defect modes in magnonic
      crystals as well as for future magnetic recording. 

PMID- 25601555
TI  - Large number of putative chemoreception and pheromone biosynthesis genes revealed
      by analyzing transcriptome from ovipositor-pheromone glands of Chilo
      suppressalis.
AB  - The chemoreception role of moth ovipositor has long been suggested, but its
      molecular mechanism is mostly unknown. By transcriptomic analysis of the female
      ovipositor-pheromone glands (OV-PG) of Chilo suppressalis, we obtained 31
      putative chemoreception genes (9 OBPs, 10 CSPs, 2 ORs, 1 SNMP, 8 CXEs and 1 AOX),
      in addition to 32 genes related to sex pheromone biosynthesis (1 FAS, 6 Dess, 10
      FARs, 2 ACOs, 1 ACC, 4 FATPs, 3 ACBPs and 5 ELOs). Tissue expression profiles
      further revealed that CsupCSP2 and CsupCSP10 were OV-PG biased, while most
      chemoreception genes were highly and preferably expressed in antennae. This
      suggests that OV-PG employs mostly the same chemoreception proteins as in
      antennae, although the physiological roles of these proteins might be different
      in OV-PG. Of the 32 pheromone biosynthesis related genes, CsupDes4, CsupDes5 and
      CsupFAR2 are strongly OV-PG biased, and clustered with functionally validated
      genes from other moths, strongly indicating their involvement in specific step of
      the pheromone biosynthesis. Our study for the first time identified a large
      number of putative chemoreception genes, and provided an important basis for
      exploring the chemoreception mechanisms of OV-PG in C. suppressalis, as well as
      other moth species. 

PMID- 25601556
TI  - Simultaneous resection for rectal cancer with synchronous liver metastasis is a
      safe procedure.
AB  - BACKGROUND: One quarter of colorectal cancer patients will present with liver
      metastasis at the time of diagnosis. Recent studies have shown that simultaneous
      resections are safe and feasible for stage IV colon cancer. Limited data are
      available for simultaneous surgery in stage IV rectal cancer patients. METHODS:
      One hundred ninety-eight patients underwent surgical treatment for stage IV
      rectal cancer. In 145 (73%) patients, a simultaneous procedure was performed.
      Fifty-three (27%) patients underwent staged liver resection. A subpopulation of
      69 (35%) patients underwent major liver resection (3 segments or more) and 30
      (44%) patients with simultaneous surgery. RESULTS: The demographics of the 2
      groups were similar. Complication rates were comparable for simultaneous or
      staged resections, even in the group subjected to major liver resection. Total
      hospital stay was significantly shorter for the simultaneously resected patients
      (P < .01). CONCLUSIONS: Simultaneous resection of rectal primaries and liver
      metastases is a safe procedure in carefully selected patients at high-volume
      institutions, even if major liver resections are required.

PMID- 25601558
TI  - Surgical resident perspective on deceased donor organ procurement.
AB  - BACKGROUND: Deceased donor organ procurement provides unparalleled opportunity
      for surgical residents with extensive surgical exposure. We hypothesize that
      surgical residents regard organ donation positively and organ procurement
      enhances their education. METHODS: We conducted an institutional review board
      approved anonymous national survey to evaluate organ procurement experiences and
      attitudes of general surgical residents. RESULTS: Three hundred ninety-seven
      residents representing all postgraduate years responded, with 97% completion
      rate. Organ procurement increased with training level (92% seniors vs. 53%
      interns). Over 85% agree organ procurement is a good educational and operative
      experience, and 73% believe that it will benefit their future surgical career.
      About 68% agree that organ procurement provided knowledge of anatomy and
      exposures; under 10% felt organ procurement could be duplicated with simulation.
      Presence of transplant program did not affect attitudes or experience. Eighty
      eight percent women versus77% men plan to donate their own organs. CONCLUSION:
      Results indicate that surgical residents value organ procurement, and it remains
      an essential encounter that applies to general surgery.

PMID- 25601557
TI  - Tumor size predicts long-term survival in colon cancer: an analysis of the
      National Cancer Data Base.
AB  - BACKGROUND: American Joint Committee on Cancer uses tumor size for "T" staging of
      many solid tumors for its effect on prognosis. However, tumor size has not been
      incorporated in tumor (T), nodal status (N), metastasis (M) staging for colon
      cancer. Hence, the National Cancer Data Base was used to determine whether tumor
      size correlates with TNM staging and survival. METHODS: For the 300,386 patients,
      tumor size was divided into S1 (0 to 2 cm), S2 (>2 to 4 cm), S3 (>4 to 6 cm), and
      S4 (>6 cm). Statistical comparison was done for TNM stage, grade, and nodal
      status with tumor size. Kaplan-Meier survival analysis was done for each "S"
      stage. RESULTS: Of the 300,386 patients, 13% were classified as S1, 39% S2, 30%
      S3 and 18% as S4. Right colon was the most common site (48%). Tumor size
      positively correlated with grade, T stage, and nodal stage. Tumor size was
      inversely associated with survival. CONCLUSION: Tumor size is positively
      correlated with important prognostic factors and negatively impacted survival.

PMID- 25601559
TI  - Gastric bypass improves survival compared with propensity-matched controls: a
      cohort study with over 10-year follow-up.
AB  - BACKGROUND: The purpose of this study is to evaluate the long-term survival
      following gastric bypass using propensity-matched controls. METHODS: We
      identified all patients who either received a gastric bypass (GBP) or met
      criteria to receive a GBP between January 1, 2002 and December 31, 2003.
      Propensity matching was performed. Long-term, all-cause mortality data were
      collected and evaluated using Kaplan-Meier curves. RESULTS: Four hundred thirty
      GBP cases and 5,323 controls were identified from the enrollment period.
      Ultimately, 802 cases and controls (1:1 matching, 93.2% match rate) were
      identified using propensity matching. Median follow-up was similar between
      groups. Overall mortality was lower for the GBP group (odds ratio .48, 95%
      confidence interval .29 to .78). GBP demonstrated significantly increased
      survival when compared with controls (P = .002). Similar patterns were noted
      among diabetics. CONCLUSION: We have demonstrated that gastric bypass provides a
      clear long-term survival advantage compared with nonsurgical propensity-matched
      controls.

PMID- 25601561
TI  - Coupling unstable agents in biological control.
AB  - It has long been a goal of farm policy to manage production in such a way that
      expensive off-farm inputs and negative environmental consequences can be
      simultaneously minimized. One generalized philosophy that has gained currency in
      recent years is autonomous pest control, in which complex ecological interactions
      are encouraged to maintain the ecosystem in a state of permanence with the pest
      below economic thresholds. Early experience with biological control was hampered
      significantly by the inherent instability of many of the control agents,
      suggesting that pursuit of the autonomous strategy could be difficult. Here we
      show that combining two unstable two-dimensional systems (pest-predator and pest
      pathogen) produces a stable three-dimensional system (pest-predator-pathogen)
      that is robust to perturbations in initial conditions. Contrary to expectations,
      the inclusion of negative interactions, which are arguably a necessary
      consequence of increased complexity, can stabilize unstable conditions and rescue
      biological control of simpler, ineffective pest management systems. 

PMID- 25601562
TI  - Determination of left atrium volume by fast anatomical mapping and intracardiac
      echocardiography. The contribution of respiratory gating.
AB  - BACKGROUND: The anatomical reconstruction of the left atrium (LA) and pulmonary
      veins with fast anatomical mapping (FAM) and intracardiac echocardiography (ICE)
      using the Carto 3 system (Biosense Webster, Inc) provides real-time guidance to
      catheter manipulation during ablation of atrial fibrillation (AF). The present
      study compared real-time LA volume reconstruction using FAM and ICE. In addition,
      the contribution of respiratory gating was assessed. METHODS: LA reconstruction
      was created using FAM and ICE in 60 consecutive patients (mean age 63 +/- 9
      years; 38 males) undergoing AF ablation. In the first 30 patients, FAM and ICE
      were performed without respiratory gating. In the last 30 patients, FAM and ICE
      were performed with respiratory gating. RESULTS: LA volumes determined by FAM
      were larger than those obtained with ICE in the absence of respiratory gating (n
      = 30; 129.5 +/- 44 vs 110 +/- 39.7 cm(3); p = 0.001). However, respiratory gating
      reduced LA volume determined with FAM by 17.7 +/- 6.6% resulting in similar LA
      volumes to those obtained using ICE [n = 30; 100 +/- 29.7 (61-154) vs 101.53 +/-
      40.1 (56-212) cm(3), p = 0.7, NS]. CONCLUSIONS: In the absence of respiratory
      gating, LA volumes determined by FAM are larger than those obtained with ICE. In
      contrast, with the addition of respiratory gating, both FAM and ICE provide
      similar real-time LA volumes.

PMID- 25601560
TI  - Sub-cellular location of FtsH proteases in the cyanobacterium Synechocystis sp.
      PCC 6803 suggests localised PSII repair zones in the thylakoid membranes.
AB  - In cyanobacteria and chloroplasts, exposure to HL damages the photosynthetic
      apparatus, especially the D1 subunit of Photosystem II. To avoid chronic
      photoinhibition, a PSII repair cycle operates to replace damaged PSII subunits
      with newly synthesised versions. To determine the sub-cellular location of this
      process, we examined the localisation of FtsH metalloproteases, some of which are
      directly involved in degrading damaged D1. We generated transformants of the
      cyanobacterium Synechocystis sp. PCC6803 expressing GFP-tagged versions of its
      four FtsH proteases. The ftsH2-gfp strain was functional for PSII repair under
      our conditions. Confocal microscopy shows that FtsH1 is mainly in the cytoplasmic
      membrane, while the remaining FtsH proteins are in patches either in the
      thylakoid or at the interface between the thylakoid and cytoplasmic membranes. HL
      exposure which increases the activity of the Photosystem II repair cycle led to
      no detectable changes in FtsH distribution, with the FtsH2 protease involved in
      D1 degradation retaining its patchy distribution in the thylakoid membrane. We
      discuss the possibility that the FtsH2-GFP patches represent Photosystem II
      'repair zones' within the thylakoid membranes, and the possible advantages of
      such functionally specialised membrane zones. Anti-GFP affinity pull-downs
      provide the first indication of the composition of the putative repair zones. 

PMID- 25601563
TI  - Coupling of disulfide bond and distal histidine dissociation in human ferrous
      cytoglobin regulates ligand binding.
AB  - Earlier kinetics studies on cytoglobin did not assign functional properties to
      specific structural forms. Here, we used defined monomeric and dimeric forms and
      cysteine mutants to show that an intramolecular disulfide bond (C38-C83) alters
      the dissociation rate constant of the intrinsic histidine (H81) (~1000 fold),
      thus controlling binding of extrinsic ligands. Through time-resolved spectra we
      have unequivocally assigned CO binding to hexa- and penta-coordinate forms and
      have made direct measurement of histidine rebinding following photolysis. We
      present a model that describes how the cysteine redox state of the monomer
      controls histidine dissociation rate constants and hence extrinsic ligand
      binding.

PMID- 25601564
TI  - MiR-155 targets TP53INP1 to regulate liver cancer stem cell acquisition and self
      renewal.
AB  - In liver cancer, miR-155 up-regulation can regulate cancer-cell invasion.
      However, whether miR-155 expression is associated with liver cancer stem cells
      (CSCs) remains unknown. Here, we show that miR-155 expression is up-regulated in
      tumor spheres. Knock-down of miR-155 resulted in suppression of tumor sphere
      formation, through a decrease in the proportion of CD90(+) and CD133(+) CSCs and
      in the expression of Oct4, whereas miR-155 overexpression had the opposite
      effect. TP53INP1 was determined to be involved in the CSCs-like properties that
      were regulated by miR-155. Thus, miR-155 may play an important role in promoting
      the generation of stem cell-like cells and their self-renewal by targeting the
      gene TP53INP1. 

PMID- 25601566
TI  - Unfolded DapA forms aggregates when diluted into free solution, confounding
      comparison with folding by the GroEL/GroES chaperonin system.
AB  - A recent hydrogen-deuterium exchange study of folding of the GroEL/GroES
      dependent bacterial enzyme DapA has suggested that the DapA folding pathway when
      free in solution may differ from the folding pathway used in the presence of the
      GroEL/GroES chaperonin. Here, we have investigated whether DapA aggregation might
      be occurring in free solution under the conditions of the exchange experiment, as
      this would confound interpretation of the pathway predictions. Dynamic light
      scattering (DLS) data, sedimentation analysis and refolding yield indicate that
      significant aggregation occurs upon dilution of DapA from denaturant, bringing
      into question the earlier conclusion that different folding pathways occur in the
      absence and presence of the chaperonin system. 

PMID- 25601567
TI  - Diabetes: Hepatic lipogenesis independent of insulin in type 2 diabetes mellitus-
      a paradox clarified.

PMID- 25601565
TI  - Ssn6 has dual roles in Candida albicans filament development through the
      interaction with Rpd31.
AB  - Ssn6 is a crucial regulator of morphological transition and virulence in the
      fungal pathogen Candida albicans. Ssn6 has previously been reported to act in
      complex with the transcriptional repressor Tup1. Here, we report that Ssn6 also
      interacts with the histone deacetylase Rpd31, independently of Tup1. The
      ssn6/rpd31 double mutant strain formed elongated filaments, but failed to form
      filament extension, and this coincided with the down-regulation of the filament
      extension gene UME6. Occupancy patterns of Ssn6 and Rpd31 differed at the
      promoters of UME6 and the metabolic gene INO1. These findings indicate that, in
      C. albicans, Ssn6 has dual roles in filament development, depending on the
      interaction with Rpd31. 

PMID- 25601568
TI  - Infection: Resistance to infection--skin adipocytes in the spotlight.

PMID- 25601569
TI  - Optimization of complex medium composition for heterotrophic cultivation of
      Euglena gracilis and paramylon production.
AB  - Heterotrophic cultivation of Euglena gracilis was carried out on synthetic
      (Hutner medium) and complex cultivation media in order to optimize production of
      beta-1,3-glucan (paramylon). For preparation of complex media, various industrial
      by-products (e.g., molasses, corn steep solid, yeast extract, and beef extract)
      were used with or without addition of pure compounds [glucose, galactose,
      fructose, lactose, maltose, sucrose, and (NH4)2HPO4]. Heterotrophic cultivation
      of E. gracilis was performed in Erlenmeyer flasks and additionally confirmed
      during research in the stirred tank bioreactor. The results clearly show that E.
      gracilis can easily metabolize glucose and fructose as carbon sources and corn
      steep solid as complex nitrogen and growth factors source for biomass growth and
      paramylon synthesis. Furthermore, it was also proved that addition of (NH4)2HPO4,
      beef extract, or gibberellic acid did not have positive effect on the biomass
      growth and paramylon synthesis. After optimization of complex medium composition
      and verification in the stirred tank bioreactor, it was concluded that medium
      composed of glucose (20 g/L) and corn steep solid (30 g/L) is the most suitable
      complex medium for industrial cultivation of E. gracilis and paramylon
      production.

PMID- 25601570
TI  - Sequential pretreatment strategies under mild conditions for efficient enzymatic
      hydrolysis of wheat straw.
AB  - This work studies the sequential execution of dilute sulfuric acid (DAP) (0.1
      0.75 %, v/v) and dilute sodium hydroxide (AKP) (0.25-3 %, w/v) [i.e., DAP
      followed by AKP (DAP+AKP) and vice versa (AKP+DAP)] at low temperatures (<121 
      degrees C) and short reaction times (5-60 min) for maximizing sugar recovery in
      the enzymatic hydrolysis of wheat straw with low enzyme dosage. The pretreatment
      effectiveness was measured by the sum of the severity factors of both
      pretreatments and the saccharification yield achieved in the subsequent stage of
      enzymatic hydrolysis. Degradation compounds were quantified and mass balance
      calculations were carried out for each pretreatment sequence to verify the
      correct account of the input biomass and output products. Results show that
      sequential pretreatments (AKP+DAP and DAP+AKP) had a positive effect in enzyme
      accessibility thus improving monosaccharide yields compared to single DAP and AKP
      pretreatments. DAP+AKP achieved a high xylose yield (ca. 0.867 of theoretical) at
      the DAP stage, while no xylose monosaccharides were detected in the subsequent
      AKP. After enzyme saccharification of double-pretreated solids, the total
      monosaccharide yield was 0.786 (of theoretical). For AKP+DAP sequence, lower
      results were obtained (total monosaccharide yield 0.783 of theoretical).
      Sequential pretreatments total yields increased by 21 % compared to single
      pretreatments. AKP removed more than half of the lignin from the wheat straw in
      all cases. Acid and alkali concentrations played a relevant role in all
      pretreatment sequences, while reaction time and temperature were less important
      with an almost-linear effect on the total monosaccharide yields.

PMID- 25601571
TI  - Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction
      in collagen-induced arthritis.
AB  - OBJECTIVES: Recent studies have suggested immunomodulatory and anti-inflammatory
      effects of cannabinoid receptor 2 (CB2R) activation, which is devoid of
      psychoactivity. We have demonstrated the expression of CB2R in synovial tissue
      from patients with rheumatoid arthritis (RA), and its specific activation shows
      inhibitory effects on fibroblast-like synoviocytes. However, it is still unclear
      whether selective activation of CB2R inhibits joint inflammation or protects
      joint damage in RA. METHODS: A murine model of collagen-induced arthritis (CIA)
      was used to evaluate the therapeutic efficacy of HU-308, a selective CB2R
      agonist. The disease severity was evaluated by semi-quantitative scoring of joint
      swelling, histological assessment of joint inflammation and structure, and
      radiographic assessment of joint destruction by using digital plain radiographs
      and micro-CT scans. The concentrations of various isotypes of anti-collagen II
      antibodies in sera and the levels of cytokines in culture supernatants were
      determined by ELISA. RESULTS: Compared with vehicle treatment, protective
      treatment with intraperitoneal injection of HU-308 (0.3-1.0 mg/kg) failed to
      decrease the incidence of the development of CIA, but it effectively suppressed
      the severity of the disease. In CIA mice, treatment with HU-308 significantly
      decreased joint swelling, synovial inflammation, and joint destruction, as well
      as serum levels of anti-collagen II antibodies. In vitro, HU-308 (1-10 MUM)
      significantly suppressed the production of proinflammatory cytokines IL-6 and TNF
      alpha from lipopolysaccharide-stimulated murine peritoneal macrophages with
      intact CB2R in dose-dependent manners. HU-308 failed to elicit any inhibitory
      effect of on lipopolysaccharide-stimulated macrophages from CB2R-knockout mice.
      CONCLUSIONS: Activation of CB2R by HU-308 has therapeutic potential for RA to
      suppress synovitis and alleviate joint destruction by inhibiting the production
      of autoantibodies and proinflammatory cytokines.

PMID- 25601572
TI  - Unexpected tackifiers from isosorbide.
AB  - Molecularly well-defined tackifiers with up to 100 % bio-content were prepared
      from isosorbide and various cyclic anhydrides. These tackifiers are tacky over a
      broad temperature range and exhibit high maximum tack (ca. 2000 kPa). Structural
      modifications shift the temperature at which maximum tack is observed and change
      the viscosity of the tackifiers. 

PMID- 25601573
TI  - Age dependent levels of plasma homocysteine and cognitive performance.
AB  - Elevated plasma homocysteine (hcy) levels, also known as hyperhomocysteinemia
      (hhcy), have been associated with cognitive impairment and neurodegenerative
      disorders. Hhcy has been attributed to deficiency of B vitamins which can
      adversely affect the brain and result in memory loss and poor attention power.
      Monitoring hcy levels and the use of vitamin supplementation to treat hhcy may
      therefore prove advantageous for the prevention and management of cognitive
      impairment. With this in consideration, we measured plasma hcy, folate and
      vitamin B12 levels in 639 subjects from different age groups in two sub-regions
      of India. Cognitive function was also measured using attention span and immediate
      and delayed memory recall tests. Depression scores were obtained using the Beck
      Depression Inventory-II and functional impairment was assessed using the
      functional activities questionnaire (FAQ) score. As hhcy has also been linked to
      inflammation, plasma levels of high sensitivity C-reactive protein (hsCRP) and
      interleukin-6 (IL-6) were also measured. The results demonstrated significant
      negative correlations between hcy levels and folic acid levels, vitamin B12
      levels and cognitive performance (attention span and delayed but not immediate
      memory recall) along with significant positive correlations between hcy levels
      and depression scores and hsCRP (but not IL-6) levels. A positive correlation was
      also observed between hcy levels and FAQ scores, however this was not found to be
      significant. Based on these results, folic acid and vitamin B12 intervention in
      people with elevated hcy levels in India could prove to be effective in lowering
      hcy levels and help maintain or improve cognitive function.

PMID- 25601575
TI  - Conditioned same-sex partner preference in male rats is facilitated by oxytocin
      and dopamine: effect on sexually dimorphic brain nuclei.
AB  - Conditioned same-sex partner preference can develop in male rats that undergo
      cohabitation under the effects of quinpirole (QNP, D2 agonist). Herein, we
      assessed the development of conditioned same-sex social/sexual preference in
      males that received either nothing, saline, QNP, oxytocin (OT), or QNP+OT during
      cohabitation with another male (+) or single-caged (-). This resulted in the
      following groups: (1) Intact-, (2) Saline+, (3) QNP-, (4) OT-, (5) QNP+, (6) OT+
      and (7) QNP/OT+. Cohabitation occurred during 24h in a clean cage with a male
      partner that bore almond scent on the back as conditioned stimulus. This was
      repeated every 4 days for a total of three trials. Social and sexual preference
      were assessed four days after the last conditioning trial in a drug-free test in
      which experimental males chose between the scented familiar male and a novel
      sexually receptive female. Results showed that males from groups Intact-,
      Saline+, QNP- and OT- displayed a clear preference for the female (opposite-sex),
      whereas groups QNP+, OT+ and QNP/OT+ displayed socio/sexual preference for the
      male partner (same-sex). In Experiment 2, the brains were processed for Nissl dye
      and the area size of two sexually dimorphic nuclei (SDN-POA and SON) was compared
      between groups. Males from groups OT-, OT+ and QNP/OT+ expressed a smaller SDN
      POA and groups QNP+ and QNP/OT+ expressed a larger SON. Accordingly, conditioned
      same-sex social/sexual partner preference can develop during cohabitation under
      enhanced D2 or OT activity but such preference does not depend on the area size
      of those sexually dimorphic nuclei.

PMID- 25601574
TI  - Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult
      vocal learning.
AB  - Vocal learning underlies acquisition of both language in humans and vocal signals
      in some avian taxa. These bird groups and humans exhibit convergent developmental
      phases and associated brain pathways for vocal communication. The transcription
      factor FoxP2 plays critical roles in vocal learning in humans and songbirds.
      Another member of the forkhead box gene family, FoxP1 also shows high expression
      in brain areas involved in vocal learning and production. Here, we investigate
      FoxP2 and FoxP1 mRNA and protein in adult male budgerigars (Melopsittacus
      undulatus), a parrot species that exhibits vocal learning as both juveniles and
      adults. To examine these molecules in adult vocal learners, we compared their
      expression patterns in the budgerigar striatal nucleus involved in vocal
      learning, magnocellular nucleus of the medial striatum (MMSt), across birds with
      different vocal states, such as vocalizing to a female (directed), vocalizing
      alone (undirected), and non-vocalizing. We found that both FoxP2 mRNA and protein
      expressions were consistently lower in MMSt than in the adjacent striatum
      regardless of the vocal states, whereas previous work has shown that songbirds
      exhibit down-regulation in the homologous region, Area X, only after singing
      alone. In contrast, FoxP1 levels were high in MMSt compared to the adjacent
      striatum in all groups. Taken together these results strengthen the general
      hypothesis that FoxP2 and FoxP1 have specialized expression in vocal nuclei
      across a range of taxa, and suggest that the adult vocal plasticity seen in
      budgerigars may be a product of persistent down-regulation of FoxP2 in MMSt.

PMID- 25601576
TI  - Mechanisms of insulin resistance in the amygdala: influences on food intake.
AB  - Obesity is increasing worldwide and is triggered, at least in part, by enhanced
      caloric intake. Food intake is regulated by a complex mechanism involving the
      hypothalamus and hindbrain circuitries. However, evidences have showing that
      reward systems are also important in regulating feeding behavior. In this
      context, amygdala is considered a key extra-hypothalamic area regulating feeding
      behavior in human beings and rodents. This review focuses on the regulation of
      food intake by amygdala and the mechanisms of insulin resistance in this brain
      area. Similar to the hypothalamus the anorexigenic effect of insulin is mediated
      via PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) pathway in the
      amygdala. Insulin decreases NPY (neuropeptide Y) and increases oxytocin mRNA
      levels in the amygdala. High fat diet and saturated fatty acids induce
      inflammation, ER (endoplasmic reticulum) stress and the activation of serine
      kinases such as PKCtheta (protein kinase C theta), JNK (c-Jun N-terminal kinase)
      and IKKbeta (inhibitor of nuclear factor kappa-B kinase beta) in the amygdala,
      which have an important role in insulin resistance in this brain region.
      Overexpressed PKCtheta in the CeA (central nucleus of amygdala) of rats increases
      weight gain, food intake, insulin resistance and hepatic triglycerides content.
      The inhibition of ER stress ameliorates insulin action/signaling, increases
      oxytocin and decreases NPY gene expression in the amygdala of high fat feeding
      rodents. Those data suggest that PKCtheta and ER stress are main mechanisms of
      insulin resistance in the amygdala of obese rats and play an important role
      regulating feeding behavior. 

PMID- 25601577
TI  - A 1-night operant learning task without food-restriction differentiates among
      mouse strains in an automated home-cage environment.
AB  - Individuals are able to change their behavior based on its consequences, a
      process involving instrumental learning. Studying instrumental learning in mice
      can provide new insights in this elementary aspect of cognition. Conventional
      appetitive operant learning tasks that facilitate the study of this form of
      learning in mice, as well as more complex operant paradigms, require labor
      intensive handling and food deprivation to motivate the animals. Here, we
      describe a 1-night operant learning protocol that exploits the advantages of
      automated home-cage testing and circumvents the interfering effects of food
      restriction. The task builds on behavior that is part of the spontaneous
      exploratory repertoire during the days before the task. We compared the behavior
      of C57BL/6J, BALB/cJ and DBA/2J mice and found various differences in behavior
      during this task, but no differences in learning curves. BALB/cJ mice showed the
      largest instrumental learning response, providing a superior dynamic range and
      statistical power to study instrumental learning by using this protocol. Insights
      gained with this home-cage-based learning protocol without food restriction will
      be valuable for the development of other, more complex, cognitive tasks in
      automated home-cages.

PMID- 25601578
TI  - Modifications of carbohydrate residues in the sheep oviductal ampulla after
      superovulation.
AB  - Epithelium of oviductal ampulla was studied in normal and in superovulated sheep
      using morphologic analysis and lectin glycohistochemistry. The lining epithelium
      consisted of two types of cells, ciliated and nonciliated cells. Unlike
      superovulated samples, the nonciliated cells from control ewes showed apical
      protrusions indicating an apocrine secretory activity. The ciliated cells showed
      lectin-binding sites mainly at the level of the cilia which bound all the used
      lectins except Peanut agglutinin, suggesting the lack of glycans terminating with
      Galbeta1,3GalNAc. In superovulated specimens, the ciliated cells with high
      mannosylated glycans Concanavalin A (Con A) and GlcNAc and GalNac termini
      Griffonia simplicifolia agglutinin II (GSA II) and Dolicurus biflorus agglutinin
      (DBA) decreased. The luminal surface of nonciliated cells showed all investigated
      sugar residues in controls, whereas it was lacking in high mannosylated (Con A)
      and terminal GalNAcalpha1,3(LFucalpha1,2)Galbeta1,3/4GlcNAcbeta1 sequence (DBA)
      in superovulated ewes. Apical protrusions from control ampullae nonciliated cells
      showed glycans containing mannose, GlcNac, GalNAc, galactose, and alpha2,3-linked
      sialic acid (Con A, KOH-sialidase- Wheat germ agglutnin [WGA], GSA II, SBA,
      Griffonia simplicifolia agglutinin-isolectin B4 [GSA I-B4], Maackia amurensis
      agglutinin II [MAL II]). The supranuclear cytoplasm of nonciliated cells
      expressed terminal GlcNAc (GSA II) in all specimens, also O-linked glycans (mucin
      type glycans) with GalNAc and sialic acid termini (Helix pomatia agglutinin [HPA]
      and MAL II) in control animals, and also N-linked glycans with fucose, galactose,
      lactosamine, and alpha2,3-linked sialic acid termini (Ulex europaeus agglutinin I
      [UEA I], GSA I-B4, Ricinus communis agglutinin120 [RCA120], and Sambucus nigra
      agglutinin [SNA] ) in superovulated ewes. These results report for the first time
      that the superovulation treatment affects the secretory activity and the glycan
      pattern of the epithelium lining the sheep oviductal ampulla. 

PMID- 25601579
TI  - The role of vitamin D in psoriasis: a review.
AB  - BACKGROUND AND OBJECTIVE: Psoriasis is a common, chronic autoimmune inflammatory
      skin disorder, which has potential systemic complications and is clinically
      defined by sharply demarcated, erythematous patches and plaques covered by a
      characteristic silvery white scale. Topical corticosteroids have widely been
      regarded as the mainstay first line of treatment. Recently, topical vitamin D
      analogs have been added to the first-line treatment repertoire as well, either as
      monotherapy or in combination with topical steroids due to synergistic,
      complementary effectiveness. In this paper, we review the role of vitamin D in
      the pathophysiology and treatment of psoriasis. METHODS: A comprehensive search
      of the Cochrane Library, MEDLINE, and PUBMED databases were performed to identify
      relevant basic science and clinical trial literature investigating the role of
      vitamin D in psoriasis. Primary endpoints in clinical trials were largely based
      on clinical improvement as assessed by the psoriasis area severity index score or
      physician's global assessment. RESULTS AND CONCLUSION: The role of vitamin D in
      psoriasis is complex and extensive. Oral and topical vitamin D therapies provide
      comparable efficacies to corticosteroids when used as monotherapy and may be
      superior when used in combination with a potent topical steroid. Additionally
      topical vitamin D analogs demonstrate a favorable safety profile with "steroid
      sparing" effects. Thus, topical vitamin D derivatives should be considered an
      indispensable component of the current physician's arsenal in the treatment of
      psoriasis.

PMID- 25601580
TI  - Erratum to: An endoscopic and anatomical approach to the septal papillary muscle
      of the conus.

PMID- 25601581
TI  - Single-molecule magnet behavior in three cyano-bridged heterometallic Fe(III)
      Ni(II) clusters.
AB  - One trinuclear and two tetranuclear cyanide-bridged Fe(III)-Ni(II) complexes were
      synthesized via treatment of a tricyanometallate with divalent Ni salts in the
      presence of 1-butylimidazole, 2,2-bipyrimidyl and 1,10-phenanthroline,
      respectively. Magnetic property studies demonstrated that the three complexes
      exhibit single-molecule magnet behavior as a result of strong intracluster
      ferromagnetic coupling and weak intercluster magnetic interactions. 

PMID- 25601584
TI  - Impaired performance on advanced Theory of Mind tasks in children with epilepsy
      is related to poor communication and increased attention problems.
AB  - Children with epilepsy (CWE) have social difficulties that can persist into
      adulthood, and this could be related to problems with understanding others'
      thoughts, feelings, and intentions. This study assessed children's ability to
      interpret and reason on mental and emotional states (Theory of Mind) and examined
      the relationships between task scores and reports of communication and behavior.
      Performance of 56 CWE (8-16years of age) with below average IQ (n=17) or an
      average IQ (n=39) was compared with that of 62 healthy controls with an average
      IQ (6-16years of age) on cognition, language, and two advanced Theory of Mind
      (ToM) tasks that required children to attribute mental or emotional states to eye
      regions and to reason on internal mental states in order to explain behavior. The
      CWE-below average group were significantly poorer in both ToM tasks compared with
      controls. The CWE - average group showed a significantly poorer ability to reason
      on mental states in order to explain behavior, a difference that remained after
      accounting for lower IQ and language deficits. Poor ToM skills were related to
      increased communication and attention problems in both CWE groups. There is a
      risk for atypical social understanding in CWE, even for children with average
      cognitive function. 

PMID- 25601583
TI  - Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae)
      on pentylenetetrazole-induced kindling, oxidative stress, and cognitive
      impairment in mice.
AB  - Feretia apodanthera Del. (Rubiaceae) is extensively used in ethnomedicine in
      Cameroon and Nigeria for epilepsy, febrile convulsions, and rheumatic pains and
      for enhancing cognitive performance. The aim of the present study was to examine
      the effects of a lyophilized aqueous extract of F. apodanthera on the course of
      kindling development, kindling-induced learning deficit, oxidative stress
      markers, and cholinesterase activity in pentylenetetrazole (PTZ)-kindled mice.
      Pentylenetetrazole, 30mg/kg, induced kindling in mice after 30.00+/-1.67days. The
      aqueous extract of F. apodanthera showed dose-dependent antiseizure effects.
      Feretia apodanthera (150-200mg/kg) significantly increased the latency to
      myoclonic jerks, clonic seizures, and generalized tonic-clonic seizures. The
      extract also improved the seizure score and decreased the number of myoclonic
      jerks. Pentylenetetrazole kindling induced significant oxidative stress and
      cognitive impairment which were reversed by pretreatment with F. apodanthera in a
      dose-dependent manner. The significant decrease in cholinesterase activity
      observed in the PTZ-kindled mice was reversed by pretreatment with the F.
      apodanthera extract. The results indicated that pretreatment with the aqueous
      extract of F. apodanthera antagonizes seizures, oxidative stress, and cognitive
      impairment in PTZ-kindled mice. The aqueous extract of F. apodanthera also showed
      anxiolytic activities, but the inhibition of memory impairment was not attributed
      to the anxiolytic activities of the plant. These results thus suggest the
      potential of F. apodanthera as an adjuvant in epilepsy both to prevent seizures
      as well as to protect against seizure-induced oxidative stress and memory
      impairment. 

PMID- 25601586
TI  - Does intraoperative nerve monitoring reliably aid in staging of total
      thyroidectomies?
AB  - OBJECTIVES/HYPOTHESIS: Demonstrate whether intraoperative nerve monitoring is an
      effective tool in staging bilateral thyroid and neck surgeries in cases of
      intraoperative injury to the recurrent laryngeal nerve on the side of initial
      dissection. We hypothesized that IONM provides reliable and appropriate feedback
      on the functional status of the RLN on side of initial dissection during total
      thyroidectomy and central neck surgery. STUDY DESIGN: Case series with planned
      data collection. METHODS: All patients receiving total thyroidectomies or central
      neck surgeries were reviewed. The outcomes of patients treated whose procedures
      were staged based on intraoperative nerve monitoring are described. RESULTS: Ten
      (4.9%) of 206 procedures were staged based on unfavorable signal change including
      six patients with thyroid cancers and four with compressive substernal goiters.
      The overall signal drop in the 10 patients with unfavorable signal change was
      63%. Three patients had complete loss of signal. In the other seven patients, the
      signal dropped by a mean of 48%. In the eight patients with laryngoscopy-proven
      vocal fold paresis, the signal dropped by a mean of 68%. CONCLUSIONS:
      Intraoperative nerve monitoring results accurately indicated postoperative
      ipsilateral vocal cord dysfunction with high reliability. Intraoperative nerve
      monitoring is a reliable tool in staging thyroid surgery. LEVEL OF EVIDENCE: 4.

PMID- 25601585
TI  - Brief clinical screening for academic underachievement in new-onset childhood
      epilepsy: utility and longitudinal results.
AB  - OBJECTIVE: This study was conducted to determine the lifetime rate and
      distribution of supportive academic and educational services provided to children
      with new- or recent-onset epilepsy and typically developing controls, the
      relationship of this history to objective academic test performance, and the
      course of performance over serial evaluations (baseline and 2 and 5years later).
      METHODS: Research participants were 91 children aged 8-18 at study entry,
      including 50 youth with recent-onset epilepsy (28 focal [FE] and 22 generalized
      [GE] epilepsy) and healthy first-degree cousin controls (n=41). The sample with
      epilepsy included children with uncomplicated epilepsy and normal imaging and
      development. Lifetime history of a diversity of supportive educational services
      was determined via a structured interview with parents at the baseline study
      visit. Associations were examined between these support services and
      participants' academic performance in reading, spelling, and arithmetic (Wide
      Range Achievement Test-Revision 3 [WRAT3] [12]) during three serial study visits
      including baseline and 2 and 5years later. RESULTS: Children with epilepsy had a
      higher lifetime rate of provision of diverse academic supportive services
      compared to controls at the baseline visit (52% vs. 18%). These services
      antedated epilepsy diagnosis in the majority (80.8%) of the children with
      epilepsy. Among children with epilepsy, children who presented with academic
      services had significantly lower WRAT3 reading, spelling, and arithmetic
      performance at baseline and at 2- and 5-year follow-ups. CONCLUSION: A brief
      structured clinical interview conducted with parents identifies children with
      epilepsy who are at academic risk at the time of diagnosis, with that risk
      persisting up to 5years later.

PMID- 25601587
TI  - [Laryngeal mask : off to new horizons?].

PMID- 25601589
TI  - [Erratum to: Interdisciplinary management of trauma patients : Update 3 years
      after implementation of the S3 guidelines on treatment of patients with severe
      and multiple injuries].

PMID- 25601588
TI  - [Second generation laryngeal masks : expanded indications].
AB  - Since the development of the classic laryngeal mask airway (LMA) in the late
      1980s, there has been a continuous increase in the frequency of its use as well
      as areas of application. While contraindications to its use for elective
      procedures must be recognized, there are an increasing number of clinical studies
      on expanded indications for the use of supraglottic airway (SGA) devices,
      particularly those of the second generation. The present article describes the
      added features of the second generation LMAs, with special emphasis on the
      behavior of these devices in position and performance tests. An appraisal is
      conducted based on the currently available literature on the value of the utility
      for indications, such as prolonged use, laparoscopic surgery, obesity, prone
      position and Cesarean section. 

PMID- 25601590
TI  - [Intravascular volume therapy].

PMID- 25601591
TI  - Potential of neural stem cell-based therapies for Alzheimer's disease.
AB  - Alzheimer's disease (AD), known to be a leading cause of dementia that causes
      heavy social and financial burdens worldwide, is characterized by progressive
      loss of neurons and synaptic connectivity after depositions of amyloid-beta
      (Abeta) protein. Current therapies for AD patients can only alleviate symptoms
      but cannot deter the neural degeneration, thus providing no long-term recovery.
      Neural stem cells (NSCs), capable of self-renewal and of differentiation into
      functional neurons and glia, have been shown to repair damaged networks and
      reverse memory and learning deficits in animal studies, providing new hope for
      curing AD patients by cell transplantation. Under AD pathology, the
      microenvironment also undergoes great alterations that affect the propagation of
      NSCs and subsequent therapeutic efficiency, calling for measures to improve the
      hostile environment for cell transplantation. This article reviews the
      therapeutic potential of both endogenous and exogenous NSCs in the treatment of
      AD and the challenges to application of stem cells in AD treatment, particularly
      those from the microenvironmental alterations, in the hope of providing more
      information for future research in exploiting stem cell-based therapies for AD.
      (c) 2015 Wiley Periodicals, Inc. 

PMID- 25601592
TI  - Identification and management of noncompliance in atrial fibrillation patients
      receiving dabigatran: the role of a drug monitor.
AB  - BACKGROUND: Noncompliant patients might be at risk of thromboembolism because of
      the short half-life and rapid offset of dabigatran etexilate. The assessment and
      management of dabigatran noncompliance should be optimized. METHODS AND RESULTS:
      A total of 150 nonvalvular atrial fibrillation patients receiving dabigatran were
      prospectively enrolled and followed for drug compliance and persistence.
      Noncompliance was identified by questionnaires and interviews. The hemoclot
      thrombin inhibitor (HTI) assay was used for monitoring the plasma dabigatran
      levels. Sixteen patients were noncompliant (10.7%). None of the clinical
      characteristics were significantly relevant to noncompliance after multivariate
      analysis. The dabigatran plasma level based on HTI was the only independent
      predictor of noncompliance (odds ratio: 0.97 per ng/mL, P = 0.003). The
      prothrombin time (PT), international normalized ratio of PT (INR [PT]), and
      activated partial thromboplastin time did not differ between compliant and
      noncompliant patients. During the follow-up, the persistent prescription of
      dabigatran was noted in 75% of noncompliant patients without improvement in
      compliance. The drug discontinuation rate was higher in the noncompliant than
      compliant patients (6.7% vs. 25%, P = 0.035). None of the patients in either
      group received warfarin after discontinuing dabigatran. CONCLUSIONS: The
      assessment and management of dabigatran noncompliance is generally ignored in
      clinical practice. The measurement of dabigatran plasma levels by HTI could be a
      reliable and simple method to identify noncompliant patients.

PMID- 25601593
TI  - Classification tree analysis to examine influences on colorectal cancer
      screening.
AB  - PURPOSE: Identifying correlates of colorectal cancer screening (CRCS) is critical
      for cancer control and prevention. Classification tree analysis (CTA) is a
      potentially powerful analytic tool that can identify distinct population
      subgroups for which CRCS is influenced by any number of multivariable
      interactions. This study used CTA to identify correlates of CRCS for exclusive
      population subgroups. METHODS: Data were obtained from the 2007 Health
      Information National Trends Survey (HINTS) and analyzed in 2014. CTA was employed
      to determine the association between demographic (n = 11), psychosocial (n = 6),
      and numeracy (n = 3) variables and CRCS status of adults >=50 years (n = 3,769).
      RESULTS: Overall CRCS rate was 66.9 %. Level of doctor avoidance (three
      categories) was the initial splitting variable, leading to a total of 21 terminal
      node subgroups of CRCS utilization: (1) avoid doctor, not for fear of
      illness/death [n = 625 (16.5 %), four subgroups]; (2) avoid doctor, fear
      illness/death [n = 366 (9.7 %), two subgroups]; (3) do not avoid doctor [n =
      2,778 (73.7 %), 15 subgroups]. CONCLUSIONS: Doctor avoidance was an important
      behavioral influence on CRCS adherence. Use of CTA to identify unique
      characteristics within population subgroups has merit for tailoring future
      intervention strategies. Community-based approaches may be effective for reaching
      individuals who avoid routine doctor visits.

PMID- 25601594
TI  - Pressure-sensitive reaction yield of the TePixD blue-light sensor protein.
AB  - The effect of pressure on the dissociation reaction of the TePixD decamer was
      investigated by high-pressure transient grating (TG). The TG signal intensity
      representing the dissociation reaction of the TePixD decamer significantly
      decreased by applying a relatively small pressure. On the other hand, the
      reaction rate increased with increasing pressure. The equilibrium between the
      pentamer and the decamer was investigated by high-pressure dynamic light
      scattering. The results indicated that the fraction of the decamer slightly
      increased in the high-pressure region. From these measurements, it was concluded
      that the pressure-dependent signal intensity originated from the decrease of the
      quantum yield of the dissociation reaction of the decamer, indicating that this
      reaction efficiency is very sensitive to pressure. Using densimetry at high
      pressures, the compressibility was found to be pressure dependent even in a
      relatively low pressure range. We attributed the origin of the pressure-sensitive
      reaction yield to the decrease of compressibility at high pressure. Because the
      compressibility is related to the volume fluctuation, this observation suggests
      that the driving force for this reaction is fluctuation of the protein. The
      relationship between the cavities at the interfaces of the monomer units and the
      reactivity is also discussed. 

PMID- 25601595
TI  - Crystal-plane-dependent metal-support interaction in Au/TiO2.
AB  - Metal-support interactions between Au and TiO2 are studied based on Au/TiO2
      catalysts with different TiO2 crystal planes exposed. With ex situ XPS, TEM and
      in situ DRIFTS, we have investigated the crystal-plane-dependent metal-support
      interaction effects on the physiochemical properties of Au/TiO2 catalysts. Based
      on the structural characterization and spectroscopic results, we can observe
      chemical oscillations (including the electronic structures of Au nanoparticles
      and the interaction between Au/TiO2 catalysts and CO molecules) during alternate
      H2 and O2 pre-treatments. Their variation tendencies of oscillations are greatly
      dependent on the crystal planes of TiO2 and the pre-treatment temperature.
      Furthermore, their surface and electronic changes after H2 and O2 pre-treatments
      can be well correlated with their catalytic activities in CO oxidation. Electron
      transfer processes across the Au-TiO2 interface are proved to be the origin
      accounting for their changes after H2 and O2 pre-treatments. The different
      electronic structures of different TiO2 crystal planes should have relationships
      with the crystal-plane-dependent metal-support interaction effects in Au/TiO2. 

PMID- 25601596
TI  - HeartWare Ventricular Assist Device Placement in a Patient With Corrected Dextro
      Transposition of Great Arteries: A Case Report and Its Clinical Challenges.
AB  - Given the improved survival in patients with corrected dextro-transposition of
      great arteries (D-TGA), it has evolved into an adult congenital heart defect. It
      is important to understand the management and complications observed in this
      population that eventually progresses to systemic ventricular failure requiring
      cardiac transplantation. Our case focuses on the rapid right ventricle (RV)
      deterioration of a patient with corrected D-TGA following a surgical procedure
      requiring systemic support. With such patients awaiting heart transplantation,
      there are limited assist devices available for RV support and no right
      ventricular assist device is approved for destination therapy yet. Current
      indications for implantation of the HeartWare ventricular assist device (HVAD)
      are limited by the Food and Drug Administration (FDA) to the left ventricle
      support as a bridge to transplantation. However, its use in the United States for
      right-sided support has rarely been described for adult congenital defects. In
      this case, a HeartWare assist device was used to provide systemic support as a
      bridge to cardiac transplant. The size and implantation design of the HVAD makes
      it a promising option for patients with this challenging patient population and
      RV failure as a late complication. 

PMID- 25601597
TI  - An elderly woman with chest pain and constipation.

PMID- 25601598
TI  - Folate receptor targeted liposomes encapsulating anti-cancer drugs.
AB  - Among all available lipid based nanoparticulate systems, the success of liposomal
      drug delivery system is evident by the number of liposomal products available in
      the market or under advanced stages of preclinical and clinical trials. Liposome
      has the ability to deliver chemotherapeutic agents to the targeted tissues or
      even inside the cancerous cells by enhanced intracellular penetration or improved
      tumour targeting. In the last decade, folate receptor mediated tumour targeting
      has emerged as an attractive alternative method of active targeting of cancer
      cells through liposomes due to its numerous advantages over other targeting
      methods. Folate receptors, also known as folate binding proteins, allow the
      binding and internalization of folate or folic acid into the cells by a method
      called folate receptor mediated endocytosis. They have restricted presence in
      normal cells and are mostly expressed during malignant transformation. In this
      review article, folate receptor targeting capability of liposomes has been
      described. This review article has focussed on the different cancer drugs which
      have been encapsulated in folate receptor targeted liposomes and their in vitro
      as well as in vivo efficacies in several tumour models. 

PMID- 25601599
TI  - Nanostructured cubosomes as a platform for oral drug delivery.
AB  - Cubosomes are formed by amphiphilic molecules, with the bicontinuous contortions
      of inter-connecting hydrophilic and hydrophobic domains. The inner cubic-phase
      structure of cubosomes makes it an attractive drug-delivery system in
      pharmaceutical applications. This review mainly describes the potential
      applications of cubosomes as a drug delivery system for oral administration,
      highlights the mechanisms involved in the transcellular transport and digestive
      process, challenges involved in formulation development and evaluations of the in
      vivo and in vitro study. As pointed out throughout this review, a number of
      critical points on cubosome products need to be solved in order to attain
      practical applications. 

PMID- 25601601
TI  - Lipid nanoparticles for the delivery of biopharmaceuticals.
AB  - Biopharmaceuticals comprise therapeutic protein-based, nucleic acids and cell
      based products. According to their therapeutic success, the clinical use of these
      products has been growing. Therefore, the development of efficient
      biopharmaceuticals delivery systems, which overcome their limitations for
      administration, remains an excellent prospect for pharmaceutical technologists.
      In this area, lipid nanoparticles have been increasingly recognized as one of the
      most promising delivery systems, due to their exclusive advantages. However, no
      clinical biopharmaceutical lipid nanoparticle-based products are yet available.
      This fact could be explained by the lack or failure of in vivo studies, regarding
      stability and toxicological concerns, and also by the complex regulatory issues
      that must be accomplished. The present review article focuses on the different
      classes of biopharmaceuticals, their characteristics and limitations for
      administration. A state of the art regarding the use of lipid nanoparticles to
      improve biopharmaceuticals delivery is presented and a critical prospect of the
      future directions that should be addressed by pharmaceutical technologists is
      also discussed. 

PMID- 25601600
TI  - Proliposomes for oral delivery: progress and challenges.
AB  - Proliposomes are phospholipid based drug delivery systems that are finding
      important applications in the field of pharmaceutics. Proliposomes have been
      extensively studied as a potential carrier for oral delivery of drugs with poor
      bioavailability, but the mechanism of absorption and cellular uptake pathways has
      not yet been clearly understood. An in-depth insight into the physical and
      biological behavior of proliposomes is necessary for designing an effective
      delivery system for enhancing the availability of drug at the intended site.
      Reformulation of sub optimal drugs using proliposomes has given an opportunity to
      improve the therapeutic indices of various drugs predominantly by altering their
      uptake mechanism. This work reviews the proliposomal drug delivery field,
      summarizes the success of proliposomes for the oral delivery of drugs with poor
      bioavailability; indicating the key issues to be addressed to affirm that
      proliposomes can effectively work as a drug carrier in clinical settings with a
      clear understanding of its behavior in biological environment, as they are now an
      established platform technology with considerable clinical acceptance. 

PMID- 25601602
TI  - Exploring the nutraceutical potential of polyphenols from black, green and white
      tea infusions - an overview.
AB  - Black, green, and white teas are the main commercial teas obtained from buds and
      leaves of Camellia sinensis (L.). The postharvest processing treatments, together
      with genotype and growing techniques, may strongly affect the chemical
      composition of the tea infusion and, thereby, its potential effects on health.
      Catechins constituted up to 30% of tea leaves dry weight. During fermentation,
      polyphenols undergo enzymatic oxidation, leading to the formation of condensed
      polymeric compounds regarded as responsible for the typical organoleptic
      properties of black tea leaves and related infusions. Scientific studies has been
      recently focusing on the possibility that tea polyphenols, particularly those of
      black and green tea, may lead to healthy properties in individuals affected by
      diseases correlated to metabolic syndrome. In vivo experiments reveal that green
      and black tea polyphenols may be able to reduce hyperglycemia and insulin
      resistance. Other works suggest that black tea polymeric products may be
      effective in decreasing blood cholesterol levels and hypertriacylglycerolemia. To
      this regard, very few data about white tea, being the rarest and the least
      handled tea, are available so far. It has been reported that white tea could show
      higher antioxidative capacity than green tea and to exert in vitro lipolytic
      activity. Considering the increasing interest towards healthy potential through
      diet and natural medicaments, the aim of the present review was to overview the
      nutraceutical potential of polyphenols from tea after various degrees of
      fermentation. 

PMID- 25601603
TI  - Polyphenols and depression: from chemistry to medicine.
AB  - Polyphenols are an extensive group of substances present in plants. Animals and
      humans achieve them through the diet. Polyphenols have been related to several
      processes, such as oxidative stress and signaling pathways modulating gene
      expression that promote an anti-inflammatory environment. Moreover, polyphenols
      also have a possible role in the protection of several diseases, including major
      depression. Depression is an important public-health problem with a
      multifactorial etiology and lots of pathways that can be altered in affected
      subjects. Moreover, this disease can be affected by exercise, sleep and diet.
      There are animal works studying polyphenols and depression, but human studies are
      scarce. This review summarizes recent evidences in relation to the effects of
      polyphenols as antidepressant agents in the depression. 

PMID- 25601604
TI  - The effect of on-demand caffeine consumption on treating patients with premature
      ejaculation: a double-blind randomized clinical trial.
AB  - Premature ejaculation (PE) is an important and common sexual issue in male
      adults, since its etiology is still unknown. There are many suggested treatments
      such as paroxetine, clomipramine, dapoxetine, tramadol and topical agents; all of
      them have stigma or considerable side effects. Therefore, present study aimed to
      examine the effect of on-demand caffeine consumption on treating patients with
      PE. In this double blind RCT, 40 otherwise healthy individuals with PE were
      allocated into 2 groups of caffeine and placebo group. The caffeine group
      received 100 mg encapsulated caffeine for 3 weeks, 2 hours prior to each
      intercourse. Intravaginal ejaculation latency time (IELT) and index of sexual
      satisfaction (ISS) were measured before and after treatment in both groups.
      Suitable statistical analysis was performed. (Registration code:
      IRCT2013091614677N1). Mean age of the participants was 39.88+/-8.72 years. No
      significant difference was found between pre-treatment and post-treatment values
      of both IELT and ISS in the placebo group, but significant difference was seen in
      post treatment values between our two groups and pre-treatment and post-treatment
      values of the caffeine group (IELT: 144s vs 312s, p<0.001 and ISS: 77 vs 97,
      p<0.001; respectively). Furthermore, high significant correlation was found in
      post-treatment values (r>0.07, p<0.05). There are negligible scientific evidences
      regarding the beneficial effects of caffeine on several aspects of sexual life,
      which makes comparison impossible. Considering the fact that caffeine is a well
      known and widely used drug in common disease, using this compound will not result
      in any stigma. Our study demonstrates that 100mg on-demand caffeine can
      significantly increase both IELT and ISS. Furthermore, the slope of these
      increasings is correlated with each other. More studies are needed to make
      stronger conclusions. 

PMID- 25601606
TI  - Natural compounds used as therapies targeting to amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease that occurs
      throughout the world with no racial, ethnic or socioeconomic boundaries. Despite
      its high morbidity and mortality, there are limited medications available for ALS
      that may increase survival in patients with amyotrophic lateral sclerosis by
      approximately 2-3 months. Inasmuch as negative effects of riluzole on muscle
      atrophy and wasting, weakness, muscle spasticity, dysarthria, dysphagia, and
      overall patient quality of life and its different adverse effects, much attention
      has been paid to natural products and herbal medicines. Overall scientific
      reports indicate that natural products have beneficial effects on patients with
      ALS low side effects and multiple targets. In the present paper, we review the
      scientific reports on beneficial role of natural polyphenolic compounds in
      treatment of ALS. 

PMID- 25601605
TI  - Common pathways in health benefit properties of RSV in cardiovascular diseases,
      cancers and degenerative pathologies.
AB  - Lots of epidemiological studies have put forward the beneficial effects of
      dietary polyphenols consumption in the prevention of diseases related to aging
      i.e vascular pathologies, neurodegeneration, cancers and associated inflammatory
      processes. Among polyphenols, resveratrol (trans-3,4',5- trihydroxystilbene,
      RSV), a naturally occurring stilbene widely distributed in foodstuffs such as
      grapes and wine, has been the most studied. Researches performed since the last
      decades in vitro, in animal models and in (pre)clinical studies have pointed out
      its pleiotropic health benefits by acting on multiple signaling pathways which go
      beyond its originally described direct antioxidant activity. However, its low
      bioavailability upon oral ingestion and lack of specificity may hamper the
      translation of the encouraging experimental data into human health benefits.
      Herein we provide an overview on the capacity of RSV to regulate oxidative stress
      induced signaling and to modulate key components of signal transduction pathways
      which are commonly altered in cardiovascular, neurodegenerative and cancer
      pathologies. We also have attempted to provide a comprehensive outlook on RSV
      metabolism and biological activity of its main metabolites and discussed about
      the new strategies developed to circumvent its poor bioavailability and to
      improve its therapeutic efficacy, including synthesis of new derivatives and new
      formulations for its cell delivery. 

PMID- 25601607
TI  - The role of dietary polyphenols in the management of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is an idiopathic chronic, relapsing inflammation
      of the bowel which is caused by dysregulation of the mucosal immune system.
      Polyphenols as the secondary plant metabolites universally present in vegetables
      and fruits and are the most abundant antioxidants in the human diet. There is
      evidence demonstrating the beneficial health effects of dietary polyphenols. This
      review criticizes the potential of commonly used polyphenols including apple
      polyphenol, bilberry anthocyanin, curcumin, epigallocatechin-3-gallate (EGCG) and
      green tea polyphenols, naringenin, olive oil polyphenols, pomegranate polyphenols
      and ellagic acid, quercetin, as well as resveratrol specifically in IBD with an
      emphasis on cellular mechanisms and pharmaceutical aspects. Scientific research
      confirmed that dietary polyphenols possess both protective and therapeutic
      effects in the management of IBD mediated via down-regulation of inflammatory
      cytokines and enzymes, enhancing antioxidant defense, and suppressing
      inflammatory pathways and their cellular signaling mechanisms. Further
      preclinical and clinical studies are needed in order to understand safety,
      bioavailability and bioefficacy of dietary polyphenols in IBD patients. 

PMID- 25601608
TI  - Magnetic resonance imaging of suspected idiopathic bilateral C2 hypertrophic
      ganglioneuritis in dogs.
AB  - OBJECTIVES: To report the magnetic resonance imaging and clinical features of
      suspected idiopathic bilaterally symmetric hypertrophic ganglioneuritis affecting
      the C2 nerve roots. METHODS: Retrospective analysis of case records of dogs with
      imaging findings suggestive of idiopathic bilateral C2 neuritis. Data analysed
      included signalment, history, clinical signs, clinical pathology results and
      magnetic resonance imaging findings. Nerve root enlargement and spinal cord
      changes were classified as clinically significant or incidental, and further
      graded as mild, moderate or severe based on the degree of spinal cord
      distortion/compression. Imaging features were also correlated with severity of
      neurological deficits. RESULTS: Twelve dogs, including nine Staffordshire bull
      terriers showed magnetic resonance imaging features suggestive of idiopathic
      hypertrophic neuritis of C2 nerve roots. Findings were considered incidental
      (4/12) or clinically significant (8/12) based on prior neurological examination.
      Changes were best visualised on transverse images at the level of the C1-2
      intervertebral foramina. The degree of associated spinal cord compression
      subjectively correlated with the severity of the neurological deficits. All cases
      with clinically significant lesions that were treated with corticosteroids
      responded favourably. CLINICAL SIGNIFICANCE: Bilaterally symmetric C2 neuritis
      likely represents idiopathic hypertrophic ganglioneuritis. Staffordshire bull
      terriers appear over represented. Immunosuppressive doses of corticosteroids
      should be considered for clinically significant lesions.

PMID- 25601609
TI  - Hepatitis B virus infection status and risk of type 2 diabetes mellitus: A meta
      analysis.
AB  - AIM: Whether hepatitis B virus (HBV) infection increases the risk of type 2
      diabetes mellitus (T2DM) is controversial. We carried out a meta-analysis to
      evaluate the association between HBV infection status and the risk of T2DM.
      METHODS: The PubMed, Embase and Ovid databases were searched for relevant studies
      on an association between HBV infection and the risk of diabetes. Methodological
      quality was assessed using the adapted Newcastle-Ottawa Quality Assessment Scale.
      A fix- or random-effects model was used to summarize odd ratios (OR) and 95%
      confidence intervals (CI). RESULTS: We included seven cohort studies, four case
      control and four cross-sectional studies, involving 118 530 participants. The
      prevalence of T2DM differs by HBV infection status. Pooled estimators indicated a
      nearly twofold excess T2DM risk with hepatitis B cirrhosis (HBC) status. The
      summary OR of the risk of T2DM for HBC patients was 1.99 (95% CI, 1.08-3.65) when
      compared with the non-HBV individuals, and 1.74 (95% CI, 1.43-2.13) when compared
      with non-cirrhotic chronic hepatitis B (NC-CHB) patients. In contrast, no
      significant correlation was found between asymptomatic HBV carriers or NC-CHB
      patients and the incidence of diabetes, compared with non-HBV controls.
      CONCLUSION: Our findings suggest that while HBV itself may not be pro-diabetic,
      the HBV-derived cirrhosis is an independent risk factor for T2DM.

PMID- 25601610
TI  - Tumor volume as a prognostic factor was superior to the seventh edition of the pT
      classification in resectable gastric cancer.
AB  - PURPOSE: To demonstrate that the seventh edition of the tumor-node-metastasis
      (TNM) classification for gastric cancer (GC) should be updated with the tumor
      volume (pTV) for the improvement of its prognostic prediction accuracy. METHODS:
      A total of 497 stage TNM I-III GC patients who underwent curative gastrectomy
      between January 2003 and December 2007 in our center were enrolled in this study.
      pTV equals to (tumor diameter/2)(2) * pT stage. RESULTS: In the step 1
      multivariate analysis, depth of invasion (pT) was confirmed to be an independent
      prognostic factors. However, when pTV was included in the step 2 multivariate
      analysis, pTV classification became significant, while pT classification
      disappeared. pT classification was substituted by pTV. For patients in each of
      the pT, significant differences in survival could always be observed among
      patients in different pTV classification. For patients in each pTV
      classification, prognosis was highly homologous between those in different pT
      classifications. TNM classification and the tumor volume-node-metastasis (TvNM)
      classification were directly compared for convenience. We found the TvNM
      classification (HR = 1.687, P < 0.001) was the most appropriately prognostic
      classification for predicting the OS of gastric cancer patients after curative
      surgery. CONCLUSIONS: pTV maybe an independent prognostic factor in overall
      survival in GC, and pTV staging system maybe more reliable than the Union
      International Center Cancer and American Joint Committee (UICC/AJCC) on cancer pT
      system for prognostic assessment. pTV should be recommended as an important
      clinicopathologic variable for enhancement the accuracy of the prognostic
      prediction of GC patients in clinic.

PMID- 25601611
TI  - Single-walled metal-organic nanotube built from a simple synthon.
AB  - A conformationally flexible triazole-carboxylic acid ligand derived from an L
      amino acid, namely, 4 H-1,2,4-triazol-4-yl-acetic acid (alphaHGlytrz), has been
      exploited to synthesize a structurally diverse and functionally intriguing metal
      organic framework with CuSiF6. The crystal structure reveals a novel single
      walled metal-organic nanotube (SWMONT), namely, {[Cu3(MU3
      OH)(H2O)3(Glytrz)3]?SiF6?8 H2O?X}infinity (1), (where X = disordered lattice
      water molecules) having a pore size as large as zeolites. Compound 1 was
      synthesized as crystals, as powder, or as layers by
      precipitation/electrodeposition. Mercury intrusion porosimetry demonstrates the
      ability of this material to store metallic mercury, after a pressure treatment,
      contrary to previous literature examples.

PMID- 25601612
TI  - Characterising the fate of nitrogenous waste from the sea-cage aquaculture of
      spiny lobsters using numerical modelling.
AB  - Although the aquaculture of spiny lobsters has been expanding since the 1970s,
      very little is known about the potential environmental impacts on water quality
      of this activity. This study quantified the production of dissolved inorganic
      nitrogen (DIN) from Australasian red spiny lobsters, Jasus edwardsii, in the
      laboratory, and these data were then used in a numerical model to predict the
      dispersal pattern of DIN from a hypothetical commercial spiny lobster farm for a
      coastal site where such a farm would typically be located. Modelling scenarios
      were set up with combinations of two different stocking densities (3 and 5 kg m(
      3)), two different diets (mussels and moist artificial diet) and three different
      feed conversion ratios (FCR = 3, 5 and 28). DIN excretion rate from unfed
      lobsters in the laboratory on average was 1.10 +/- 0.12 MUg N g(-1) h(-1) while
      feeding lobsters on mussels and artificial diet increased DIN excretion
      significantly by around eightfold and twofold, respectively. Ammonia was
      consistently the dominant contributor to measured DIN output from lobsters.
      Modelling results indicated that the mean elevated DIN from a hypothetical farm
      where the lobsters were fed with mussels ranged from 7 up to 20 MUg N L(-1) with
      increasing stocking density and FCR and was 30-150 % higher than the mean
      elevated DIN resulting from lobsters fed with artificial diet. Overall, the
      results indicated that DIN output from the hypothetical spiny lobster sea-cage
      farming is unlikely to be problematic using the FCR, stocking density, and the
      number of cages modelled at the coastal site in this study. Furthermore, feeding
      lobsters with artificial diet can help maintain a lower DIN output than seafood,
      such as mussels or trash fish.

PMID- 25601613
TI  - Characterization and environmental risk assessment of heavy metals in
      construction and demolition wastes from five sources (chemical, metallurgical and
      light industries, and residential and recycled aggregates).
AB  - Total concentrations of heavy metals (Cu, Zn, Pb, Cr, Cd, and Ni) were measured
      among 63 samples of construction and demolition (C&D) wastes collected from
      chemical, metallurgical and light industries, and residential and recycled
      aggregates within China for risk assessment. The heavy metal contamination was
      primarily concentrated in the chemical and metallurgical industries, especially
      in the electroplating factory and zinc smelting plant. High concentrations of Cd
      were found in light industry samples, while the residential and recycled
      aggregate samples were severely polluted by Zn. Six most polluted samples were
      selected for deep research. Mineralogical analysis by X-ray fluorescence (XRF)
      spectrometry and X-ray diffraction (XRD), combined with element speciation
      through European Community Bureau of Reference (BCR) sequential extraction,
      revealed that a relatively slight corrosion happened in the four samples from
      electroplating plants but high transfer ability for large quantities of Zn and
      Cu. Lead arsenate existed in the acid extractable fraction in CI7-8 and potassium
      chromium oxide existed in the mobility fraction. High concentration of Cr could
      be in amorphous forms existing in CI9. The high content of sodium in the two
      samples from zinc smelter plants suggested severe deposition and erosion on the
      workshop floor. Large quantities of Cu existed as copper halide and most of the
      Zn appeared to be zinc, zinc oxide, barium zinc oxide, and zincite. From the
      results of the risk assessment code (RAC), the samples from the electroplating
      factory posed a very high risk of Zn, Cu, and Cr, a high risk of Ni, a middle
      risk of Pb, and a low risk of Cd. The samples from the zinc smelting plant
      presented a high risk of Zn, a middle risk of Cu, and a low risk of Pb, Cr, Cd,
      and Ni.

PMID- 25601614
TI  - Emission characteristics of VOCs emitted from consumer and commercial products
      and their ozone formation potential.
AB  - The characteristics of volatile organic compounds (VOCs) emitted from several
      consumer and commercial products (body wash, dishwashing detergent, air
      freshener, windshield washer fluid, lubricant, hair spray, and insecticide) were
      studied and compared. The spray products were found to emit the highest amount of
      VOCs (~96 wt%). In contrast, the body wash products showed the lowest VOC
      contents (~1.6 wt%). In the spray products, 21.6-96.4 % of the VOCs were propane,
      iso-butane, and n-butane, which are the components of liquefied petroleum gas.
      Monoterpene (C10H16) was the dominant component of the VOCs in the non-spray
      products (e.g., body wash, 53-88 %). In particular, methanol was present with the
      highest amount of VOCs in windshield washer fluid products. In terms of the
      number of carbon, the windshield washer fluids, lubricants, insecticides, and
      hair sprays comprised >95 % of the VOCs in the range C2-C5. The VOCs in the range
      C6-C10 were predominantly found in the body wash products. The dishwashing
      detergents and air fresheners contained diverse VOCs from C2 to C11. Besides
      comprising hazardous VOCs, VOCs from consumer products were also ozone
      precursors. The ozone formation potential of the consumer and commercial spray
      products was estimated to be higher than those of liquid and gel materials. In
      particular, the hair sprays showed the highest ozone formation potential.

PMID- 25601615
TI  - Modeling of high sodium intake effects on left ventricular hypertrophy.
AB  - Many clinical studies suggest that chronic high sodium intake contributes to the
      development of essential hypertension and left ventricular (LV) hypertrophy. In
      the present study, a system-level computer model has been developed to simulate
      the long-term effects of increased sodium intake on the LV mechanical functions
      and the body-fluid homeostasis. The new model couples a cardiovascular
      hemodynamics function model with an explicit account of the LV wall thickness
      variation and a long-term renal system model. The present model is validated with
      published results of clinical studies. The results suggest that, with increased
      sodium intake, the renal system function, the plasma hormone concentrations, and
      the blood pressure adapt to new levels of equilibrium. The LV work output and the
      relative wall thickness increase due to the increase of sodium intake. The
      results of the present model match well with the patient data. 

PMID- 25601616
TI  - Microparticle shape effects on margination, near-wall dynamics and adhesion in a
      three-dimensional simulation of red blood cell suspension.
AB  - We present a 3D computational modeling study of the transport of micro-scale drug
      carriers modeled as microparticles of different shapes (spherical, oblate, and
      prolate) in whole blood represented as a suspension of deformable red blood
      cells. The objective is to quantify the effect of microparticle shapes on their
      margination, near-wall dynamics and adhesion. We observe that the near-wall
      accumulation is highest for oblate particles of moderate aspect ratio, followed
      by spherical particles, and lowest for very elongated prolate particles. The
      result is explained using micro-scale dynamics of individual particles, and their
      interaction with red blood cells. We observe that the orientation of
      microparticles in 3D space and the frequency of their collisions with red blood
      cells are the key factors affecting their margination. We show that due to
      repeated collisions with red blood cells in the presence of a bounding wall, the
      axes of revolution of oblate particles align near the plane of the shear flow,
      but those of prolate particles shift towards the vorticity axis with a wider
      distribution. Such specific orientations lead to more frequent collisions and a
      greater lateral drift for oblate particles than microspheres, but less frequent
      collisions and a reduced lateral drift for elongated prolate particles, resulting
      in the observed differences in their near-wall accumulation. Once marginated, the
      particle shape has an entirely different effect on the likelihood of making
      particle-wall contacts. We find that marginated prolate particles, due to their
      alignment along the vorticity axis and large angular fluctuations, are more
      likely to make contacts with the wall than spherical and oblate particles. We
      further simulate the adhesion between flowing microparticles and the wall in the
      presence of red blood cells, and observe that once wall contacts are established,
      the likelihood of firm adhesion is greater for disk-like particles, followed by
      elongated prolates, and microspheres. Consequently, this study suggests that the
      local hemorheological conditions near the targeted sites must be taken into
      consideration while selecting the optimum shape of micro-scale vascular drug
      carriers. 

PMID- 25601617
TI  - Validation of image analysis techniques to measure skin aging features from
      facial photographs.
AB  - BACKGROUND: Accurate measurement of the extent skin has aged is crucial for skin
      aging research. Image analysis offers a quick and consistent approach for
      quantifying skin aging features from photographs, but is prone to technical bias
      and requires proper validation. METHODS: Facial photographs of 75 male and 75
      female North-European participants, randomly selected from the Rotterdam Study,
      were graded by two physicians using photonumeric scales for wrinkles (full face,
      forehead, crow's feet, nasolabial fold and upper lip), pigmented spots and
      telangiectasia. Image analysis measurements of the same features were optimized
      using photonumeric grades from 50 participants, then compared to photonumeric
      grading in the 100 remaining participants stratified by sex. RESULTS: The inter
      rater reliability of the photonumeric grades was good to excellent (intraclass
      correlation coefficients 0.65-0.93). Correlations between the digital measures
      and the photonumeric grading were moderate to excellent for all the wrinkle
      comparisons (Spearman's rho rho = 0.52-0.89) bar the upper lip wrinkles in the
      men (fair, rho = 0.30). Correlations were moderate to good for pigmented spots
      and telangiectasia (rho = 0.60-0.75). CONCLUSION: These comparisons demonstrate
      that all the image analysis measures, bar the upper lip measure in the men, are
      suitable for use in skin aging research and highlight areas of improvement for
      future refinements of the techniques.

PMID- 25601618
TI  - Promising alternative clinical uses of prostaglandin F2alpha analogs: beyond the
      eyelashes.
AB  - Prostaglandin F2alpha analogs, commonly prescribed for glaucoma treatment, have
      been shown to induce side effects such as cutaneous hypertrichosis and
      hyperpigmentation. Therefore, these medications have theoretic applications in
      the treatment of alopecia and disorders of hypopigmentation. We reviewed the
      literature to find original studies assessing the use of prostaglandin F2alpha
      analogs in these settings. Studies and reports were analyzed in regards to
      androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo,
      and hypopigmented scarring. Based on the results of these studies, and
      consideration of pathophysiologic mechanism, the most promising applications for
      prostaglandin F2alpha analogs include androgenic alopecia, chemotherapy-induced
      alopecia, and alopecia areata concurrently treated with corticosteroids. 

PMID- 25601619
TI  - Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery
      approach.
AB  - INTRODUCTION: Cancer stem cells (CSCs) play an important role in the development
      of drug resistance, metastasis and recurrence. Current conventional therapies do
      not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer
      cells have entered a new era of treatment, where specific targeting to CSCs may
      offer superior outcomes to efficient cancer therapies. AREAS COVERED: This review
      discusses the involvement of CSCs in tumor progression and relevant mechanisms
      associated with CSCs resistance to conventional chemo- and radio-therapies. It
      highlights CSCs-targeted strategies that are either under evaluation or could be
      explored in the near future, with a focus on various nanocarrier-based delivery
      systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are
      presented in a cancer-specific way to provide a current perspective on anti-CSCs
      therapeutics. EXPERT OPINION: The field of CSCs-targeted therapeutics is still
      emerging with a few small molecules and macromolecules currently proving efficacy
      in clinical trials. However considering the complexities of CSCs and existing
      delivery difficulties in conventional anticancer therapies, CSC-specific delivery
      systems would face tremendous technical and clinical challenges. Nanocarrier
      based approaches have demonstrated significant potential in specific drug
      delivery and targeting; their success in CSCs-targeted drug delivery would not
      only significantly enhance anticancer treatment but also address current
      difficulties associated with cancer resistance, metastasis and recurrence.

PMID- 25601620
TI  - In-situ hybridization-based quantification of hTR: a possible biomarker in
      malignant melanoma.
AB  - AIMS: Telomerase is reactivated in most cancers and there is accumulating
      evidence that this is a driver event in malignant melanoma (MM). Thus, our aim
      was to evaluate if in-situ hybridization (ISH)-based quantification of telomerase
      RNA (hTR) could be used to distinguish MM from naevi, and if there was a
      correlation with the Breslow thickness. RESULTS AND METHODS: We created a tissue
      microarray (TMA) from formalin-fixed and paraffin-embedded tissue samples from 17
      MM and 23 naevi, performed ISH targeting hTR, and quantified the signals. We
      found a more than eightfold greater number of hTR signals per nucleus in the MM
      samples compared to the naevi, and a positive correlation (P = 0.0381) between
      the number of hTR signals per nucleus and the Breslow thickness. CONCLUSION:
      Quantification of hTR ISH signals clearly distinguish MM from naevi (P < 0.0001)
      and the number of signals per nucleus correlates with the Breslow thickness,
      suggesting that hTR might be a valuable biomarker in MM. Furthermore, as ISH
      based detection requires the presence of both hTR and telomerase reverse
      transcriptase (hTERT), it might be an indicator of active telomerase and thus
      have future relevance as a predictive biomarker for anti-telomerase treatment.

PMID- 25601622
TI  - [The journal in 2014].

PMID- 25601621
TI  - [Sale].

PMID- 25601623
TI  - ['Multi-moment non-invasive neurostimulation' - a controlled study of a new
      treatment for depression].
AB  - BACKGROUND: Depressive symptoms occur frequently in Dutch society. Recently a new
      method for treating depressive symptoms was introduced in the Netherlands. The
      method, known as 'multi-moment non-invasive neurostimulation' (MNNS), involves
      presenting patients with a series of photographs, each picture having a positive
      valence. The purpose of this method is to improve the mood of patients. So far,
      however, the method has not been thoroughly tested. AIM: To conduct a pilot study
      designed to compare the effectiveness of MNNS pictures with pictures from the
      International Affective Pictures System (IAPS) by means of a double-blind
      randomised controlled trial. METHOD: Thirty-three patients with depressive
      symptoms were randomly assigned to two groups, one representing the experimental
      condition (MNNS) and the other the control condition (IAPS). Patients were
      treated for six weeks in one mood-inductive session per week. The severity of the
      patients' depressive symptoms was assessed before the mood-induction treatment
      began and again at one week and at three months after the final session. RESULTS:
      Each group showed a significant reduction in depressive symptoms. There were no
      significant differences between the MNNS condition and the control condition with
      regard to the reduction of depressive symptoms over time. CONCLUSION: There was a
      marked reduction in the depressive symptoms of the patients of both groups which
      had received short-term treatments involving the viewing of pictures with a
      positive valence. This reduction was still apparent three months after the
      treatment. The positive pictures presented in the MNNS method were found to be
      just as effective in reducing depressive symptoms as the positive pictures
      presented by the IAPS.

PMID- 25601624
TI  - [The incubus phenomenon: A sleep-related condition, not to be confused with
      psychosis].
AB  - BACKGROUND: The incubus phenomenon is a paroxysmal condition characterised by
      sleep paralysis coinciding with a sensed presence and the frightening sensation
      that something or somebody is exerting pressure on the thorax. AIM: To present an
      overview of the literature on the incubus phenomenon and to provide practical
      advice regarding diagnosis and treatment. METHOD: To obtain information for our
      paper we carried out a search in PubMed and the historical literature. RESULTS:
      The incubus phenomenon is a relatively unknown condition, even though, world
      wide, it has a lifetime prevalence rate of 30% in the general population. The
      prevalence is even higher among students, psychiatric patients and patients with
      narcolepsy. It is attributed to a dissociation of the rem sleep phase and the
      subsequent intrusion of endogenously mediated percepts. The condition rarely
      requires treatment because it is self-limiting, and generally occurs only once in
      a lifetime. Repeated attacks, however, may warrant additional diagnostic testing
      with the aid of polysomnography and may require treatment with anxiolytics,
      antidepressants, anticholinergics or anti-epileptics. CONCLUSION: The incubus
      phenomenon is an intrusive condition, but, as far as we currently know, it is
      benign. Nevertheless, it is important that the condition is recognised and not
      confused with a psychotic disorder or any other type of severe mental illness.
      When necessary, it should be treated lege artis.

PMID- 25601625
TI  - [Postpartum psychosis in clinical practice: diagnostic considerations, treatment
      and prevention].
AB  - BACKGROUND: Postpartum psychosis is a severe psychiatric disease which occurs in
      the early postpartum period after 1 - 2 per 1000 deliveries. Patients with a
      history of postpartum psychosis and/or bipolar disorder are at extreme high risk
      of relapse postpartum. AIM: To discuss diagnostic considerations, treatment and
      the prevention of postpartum psychosis, and to give clinical recommendations.
      METHOD: Literature search with PubMed and relevant textbooks. RESULTS: Inpatient
      psychiatric admission enables the clinician to ensure the safety of mother and
      baby, perform physical and neurological examination, and laboratory analysis to
      exclude known organic causes for acute psychosis. Antipsychotic and lithium and
      ECT are effective treatment options. Women with postpartum psychosis compared to
      those with bipolar disorder had a substantial difference in their clinical
      outcomes and prophylaxis requirements. CONCLUSION: Inpatient screening for
      somatic (co)morbidity is essential in patients with postpartum psychosis. With
      adequate treatment, almost all patients achieve complete remission and the
      prognosis is optimistic. Initiation of prophylaxis immediately postpartum in
      women with a history of postpartum psychosis with lithium was highly effective
      for preventing postpartum relapse.

PMID- 25601626
TI  - [The morning report - an important item in the training of psychiatrists in
      residence at psychiatric hospitals].
AB  - BACKGROUND: In this article we focus on the role, function and composition of the
      morning report in the training of psychiatrists in residence at psychiatric
      hospitals. We also pay attention to the way in which the case should be presented
      in the morning report. AIM: To make some proposals regarding ways in which the
      efficiency of the morning report and the case presented in that report can be
      improved. METHOD: We studied currently available literature and publications
      about the morning report and we also drew on our own experience with the morning
      report. RESULTS: We found very few publications that dealt specifically with
      morning report in the psychiatric teaching hospital. However, our studies have
      shown that the morning report should not be regarded purely as an instrument for
      passing on care details about the patient; it should also be seen as an essential
      link in the chain of instruction required by trainee psychiatrist. On the basis
      of rhetoric, constructivism and social-constructionism, we present a model for
      case presentation. CONCLUSION: Making improvements in the quality of the morning
      report is an important way of contributing to the learning process of trainee
      psychiatrists and staff members and should therefore enhance the status of the
      psychiatric hospital as a teaching community.

PMID- 25601628
TI  - [New interventions in psychiatry: careful evaluation and a fair chance].

PMID- 25601627
TI  - [Ethical considerations regarding the use of transcranial magnetic stimulation in
      the treatment of depression].
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) has proved effective in the
      treatment of depression. However, the step that was needed to progress from
      positive research results to the actual use of TMS to treat patients has raised a
      number of ethical concerns. The concerns extend beyond matters such as the safety
      of the technique, the patient's right of access to therapy and the patient's
      informed consent; ethics are involved because the new treatment can be mind
      bending and can interfere with the patient's autonomy and decision-making
      capacity. AIM: To discuss ethical issues raised by the use of TMS in the
      treatment of depression. METHOD: We reviewed the relevant scientific literature.
      RESULTS: The effects of the treatment on the patient's genuine wishes and on his
      or her views on the efficacy of the treatment are technique-related ethical
      issues that have not yet been adequately addressed. Furthermore, the effects of
      TMS on the patient's autonomy and mental capacity and the 'last resort' argument
      in relation to the effectiveness of the therapy are context-related
      considerations that warrant further discussion. CONCLUSION: There will have to be
      more research and discussion among researchers and clinicians about specific
      ethical questions before TMS can take its rightful place in clinical practice.

PMID- 25601629
TI  - [Downbeat nystagmus - a rare side-effect of lithium carbonate].
AB  - A 52-year-old woman who had been treated with lithium carbonate for 10 years
      developed a downbeat nystagmus. The literature describes downbeat nystagmus as a
      rare side-effect of lithium carbonate. In this patient other causes of downbeat
      nystagmus were ruled out. In most cases stopping lithium carbonate does not
      alleviate the symptoms, which are often debilitating. At the moment there is no
      adequate treatment for the condition. In some cases, however, the symptoms
      subside after the patient stops taking lithium. Therefore, we consider that early
      recognition of downbeat nystagmus in patients being treated with lithium
      carbonate is vitally important.

PMID- 25601630
TI  - [Reaction on 'Involuntary medication as the intervention of choice; from
      seclusion to treatment?].

PMID- 25601631
TI  - Self-resistance mechanisms of actinomycetes producing lipid II-targeting
      antibiotics.
AB  - Glycopeptides and several lantibiotics are lipid II-targeting antibiotics
      produced by actinomycetes. To protect themselves from their own product,
      antibiotic producers developed self-resistance mechanisms. Inspection of
      different producer strains revealed that their resistance is not only based on a
      single determinant but on the synergistic action of different factors.
      Glycopeptide producers possess different ways to synthesize a modified
      peptidoglycan to prevent the binding of the glycopeptide antibiotic. One possible
      modification is the synthesis of peptidoglycan precursors terminating with a D
      alanyl-D-lactate (D-Ala-D-Lac) rather than with a D-alanyl-D-alanine (D-Ala-D
      Ala) resulting in a 1000-fold decreased binding affinity of the glycopeptide to
      its target. The reprogramming of the peptidoglycan precursor biosynthesis is
      based on the action of VanHAX or paralogous enzymes as it was shown for
      Amycolatopsis balhimycina. A second peptidoglycan modification resulting in
      glycopeptide resistance was investigated in the glycopeptide A40926 producer
      Nonomuraea ATCC 39727. Nonomuraea eliminates the glycopeptide target by
      synthesizing a peptidoglycan with 3-3 cross-linked peptide stems. The
      carboxypeptidase VanYn provides tetrapeptides which serve as substrates for the
      L,D-transpeptidase catalyzing the formation of 3-3 cross-links. The occurrence of
      3-3 cross-linked dimers is also an important feature of the lantibiotic NAI-107
      producer Microbispora ATCC PTA-5024. Moreover, the D-Ala in the fourth position
      in the acceptor peptide of muropeptides is exchanged to glycine or serine in
      Microbispora, a side reaction of the L,D-transpeptidase. Together with the
      lipoprotein MlbQ, the ABC transporter MlbYZ and the transmembrane protein MlbJ it
      might contribute to the self-resistance in Microbispora ATCC PTA-5024.

PMID- 25601632
TI  - Sirt1 protects pig oocyte against in vitro aging.
AB  - Sirtuins have been widely reported to be involved in multiple biological
      processes. However, their function during pig oocyte aging has not been reported
      yet. Here, we first identify that sirt1 expression is dramatically reduced in pig
      in vitro-aged oocytes. Furthermore, by confocal scanning and quantitative
      analysis, we find the increased frequency of spindle defects and chromosome
      misalignment, disturbed redistribution of cortical granules and mitochondria
      during oocyte in vitro-aging. Importantly, these aging-associated defective
      phenotypes can be ameliorated through resveratrol (sirt1 activator) treatment
      during pig oocyte maturation, providing the evidence for the hypothesis that
      decreased sirt1 is one of a number of factors contributing to oocyte in vitro
      aging. In summary, our data indicate a role for sirt1 in pig oocytes and uncover
      a striking beneficial effect of sirt1 expression on aged oocytes.

PMID- 25601633
TI  - Giant stick insects reveal unique ontogenetic changes in biological attachment
      devices.
AB  - A strong modification of tarsal and pretarsal attachment pads during the
      postembryonic development is described for the first time. In the exceptionally
      large thorny devil stick insect Eurycantha calcarata a functional arolium is only
      present in the immature instars, enabling them to climb on smooth surfaces,
      especially leaves. Nymphs are also characterized by greyish and hairy euplantulae
      on tarsomeres 1-4. The gradual modifications of the arolium and the euplantula of
      tarsomere 5 in the nymphal development are probably mainly related to increased
      weight. The distinct switch in the life style between the leaf-dwelling nymphal
      stages and the ground-dwelling adults results in the final abrupt change of the
      adhesive devices, resulting in a far-reaching reduction of the arolium, the
      presence of a fully-developed, elongated euplantula on tarsomere 5, and white and
      smooth euplantulae on tarsomeres 1-4. The developmental remodelling of attachment
      pads also reflects a phylogenetic pattern. The attachment devices of the earlier
      instars are similar to those found in the basalmost lineage of extant stick
      insects, Timema, which is characterized by a very large pan-shaped arolium and a
      hairy surface of the tarsal and pretarsal attachment pads. 

PMID- 25601634
TI  - The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with
      visceral fat accumulation and alterations in postprandial glucose and lipid
      metabolism.
AB  - Large-scale meta-analyses of genome-wide association studies have recently
      confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is
      associated with fasting glycemia and type 2 diabetes mellitus; however, the
      mechanism of this link was not well established. The aim of our study was to
      evaluate the functional/phenotypic differences related to rs340874 PROX1
      variants. The study group comprised 945 subjects of Polish origin (including 634
      with BMI > 25) without previously known dysglycemia. We analyzed behavioral
      patterns (diet, physical activity), body fat distribution and glucose/fat
      metabolism after standardized meals and during the oral glucose tolerance test.
      We found that the carriers of the rs340874 PROX1 CC genotype had higher
      nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower
      glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with
      subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we
      found higher accumulation of visceral fat (p < 0.02), but surprisingly lower
      daily food consumption (p < 0.001). We hypothesize that lipid metabolism
      alterations in subjects with the PROX1 CC genotype may be a primary cause of
      higher glucose levels after glucose load, since the fatty acids can inhibit
      insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our
      observations suggest that the PROX1 variants have pleiotropic effect on disease
      pathways and it seem to be a very interesting goal of research on prevention of
      obesity and type 2 diabetes mellitus. The study may help to understand the
      mechanisms of visceral obesity and type 2 diabetes mellitus risk development. 

PMID- 25601635
TI  - Effects on cognitive and clinical insight with the use of Guided Self
      Determination in outpatients with schizophrenia: A randomized open trial.
AB  - Poor insight has a negative impact on the outcome in schizophrenia; consequently,
      poor insight is a logical target for treatment. However, neither medication nor
      psychosocial interventions have been demonstrated to improve poor insight. A
      method originally designed for diabetes patients to improve their illness
      management, Guided Self-Determination (GSD), has been adapted for use in patients
      with schizophrenia (GSD-SZ). The purpose of this study was to investigate the
      effect on insight of GSD-SZ as a supplement to treatment as usual (TAU) as
      compared to TAU alone in outpatients diagnosed with schizophrenia. The design was
      an open randomized trial. The primary hypothesis was cognitive insight would
      improve in those patients who received GSD-SZ+TAU as assessed by the BCIS. We
      additionally explored whether the intervention led to changes in clinical
      insight, self-perceived recovery, self-esteem, social functioning and symptom
      severity. Assessments were conducted at baseline, and at 3-, 6- and 12-month
      follow-up. Analysis was based on the principles of intention to treat and
      potential confounders were taken into account through applying a multivariate
      approach. A total of 101 participants were randomized to GSD-SZ+TAU (n=50) or to
      TAU alone (n=51). No statistically significant differences were found on the
      cognitive insight. However, at 12-month follow-up, clinical insight (measured by
      G12 from the Positive and Negative Syndrome Scale), symptom severity, and social
      functioning had statistically significantly improved in the intervention group as
      compared to the control group. "Improving insight in patients diagnosed with
      schizophrenia", NCT01282307, http://clinicaltrials.gov/. 

PMID- 25601636
TI  - Association between antiviral treatment and extrahepatic outcomes in patients
      with hepatitis C virus infection.

PMID- 25601637
TI  - A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively
      on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling.
AB  - OBJECTIVE: Oncogenic Kras-activated robust Mek/Erk signals phosphorylate to the
      tuberous sclerosis complex (Tsc) and deactivates mammalian target of rapamycin
      (mTOR) suppression in pancreatic ductal adenocarcinoma (PDAC); however, Mek and
      mTOR inhibitors alone have demonstrated minimal clinical antitumor activity.
      DESIGN: We generated transgenic mouse models in which mTOR was hyperactivated
      either through the Kras/Mek/Erk cascade, by loss of Pten or through Tsc1
      haploinsufficiency. Primary cancer cells were isolated from mouse tumours.
      Oncogenic signalling was assessed in vitro and in vivo, with and without single
      or multiple targeted molecule inhibition. Transcriptional profiling was used to
      identify biomarkers predictive of the underlying pathway alterations and of
      therapeutic response. Results from the preclinical models were confirmed on human
      material. RESULTS: Reduction of Tsc1 function facilitated activation of
      Kras/Mek/Erk-mediated mTOR signalling, which promoted the development of
      metastatic PDACs. Single inhibition of mTOR or Mek elicited strong feedback
      activation of Erk or Akt, respectively. Only dual inhibition of Mek and PI3K
      reduced mTOR activity and effectively induced cancer cell apoptosis. Analysis of
      downstream targets demonstrated that oncogenic activity of the Mek/Erk/Tsc/mTOR
      axis relied on Aldh1a3 function. Moreover, in clinical PDAC samples, ALDH1A3
      specifically labelled an aggressive subtype. CONCLUSIONS: These results advance
      our understanding of Mek/Erk-driven mTOR activation and its downstream targets in
      PDAC, and provide a mechanistic rationale for effective therapeutic matching for
      Aldh1a3-positive PDACs.

PMID- 25601639
TI  - Transcutaneous removal of an intravenous catheter fragment using a spider FXTM
      Embolic Protection device.
AB  - Long-term use of intravenous catheters can lead to catheter fracture and
      embolization of fragments. Transcutaneous retrieval of these catheter fragments
      can be challenging because of their fragility. We report an 8-year-old boy with
      Hemophilia disease who underwent removal of intravenous Port catheter after 7
      years of use, resulting in embolization of fractured catheter fragments into the
      distal pulmonary arteries. The snare technique to pull the snared fragment into a
      sheath was unsuccessful, and it leads to further breakdown due to its fragility.
      An alternative technique using a combination of a snare kit and a Spider FXTM
      Embolic Protection Device was employed. This technique allowed the fragments to
      be secured proximally with the basket device and distally with the snare. The
      unit was then pulled through a sheath and removed from the body. To our
      knowledge, Spider FXTM Device has not been used in this way before.

PMID- 25601640
TI  - Benign intermittent upbeat nystagmus in infancy: a new clinical entity.
AB  - BACKGROUND: Upbeat nystagmus in childhood is a rare phenomenon, which is
      classically associated with neurological or anterior visual pathway dysfunction.
      METHODS: We report a series of five infants with an intermittent upbeat
      nystagmus, without any other ocular or neurological abnormality, having
      spontaneously resolved before the age of 14 months. RESULTS: Nystagmus beating
      frequency was between 1.5 and 2.5 Hz for all patients, amplitude was remarkably
      large due to a baseline position in downgaze. The nystagmus mostly occurred in
      supine position and could be triggered by head rotations in the supine position.
      Age of onset was from the first weeks of life to two months; age of resolution
      was 5-14 months. All infants underwent complete clinical examination with
      ophthalmological, oto-neurological and neurological assessments and MRI-scan.
      CONCLUSIONS: Clinical characteristics of the nystagmus suggest an involvement of
      the otolithic system, with a secondary recalibration of the vestibulo-ocular
      pathways; however, no obvious vestibular abnormality was found. The
      pathophysiology of this nystagmus therefore remains unclear.

PMID- 25601641
TI  - B-chromosome and V-shaped spot asymmetry in the common frog (Rana temporaria L.)
      populations.
AB  - The common frog Rana temporaria is characterised by a large variety of
      colorations and dorsal patterns manifested by a V-shaped spot, which differs in
      the form, the number of elements and in the regularity. Some populations of R.
      temporaria are polymorphic for B-chromosome. V-shaped spot asymmetry and B
      chromosome occurrence was studied in seven R. temporaria populations inventoried
      from Belarus country. The analysis of the dorsal V-shaped spot pattern asymmetry
      in brown frog populations implies that the persistence of additional chromosomes
      in populations may be one of the factors disturbing the developmental stability
      of some individuals. Although, Bs may confer some selective advantage to their
      carriers, which makes them react differently to environmental changes from do non
      carriers.

PMID- 25601638
TI  - Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women
      from a fertility clinic.
AB  - Total hair mercury (Hg) was measured among 205 women undergoing in vitro
      fertilization (IVF) treatment and the association with prospectively collected
      IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62ppm,
      range: 0.03-5.66ppm) correlated with fish intake (r=0.59), and exceeded the
      recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed
      models with random intercepts accounting for within-woman correlations across
      treatment cycles were used to evaluate the association of hair Hg with IVF
      outcomes adjusted for age, body mass index, race, smoking status, infertility
      diagnosis, and protocol type. Hair Hg levels were not related to ovarian
      stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or
      to fertilization rate, embryo quality, clinical pregnancy rate or live birth
      rate. 

PMID- 25601642
TI  - Characterization and biotransformation in the plasma and red blood cells of
      V(IV)O(2+) complexes formed by ceftriaxone.
AB  - The coordination mode and geometry in aqueous solution of oxidovanadium(IV)
      complexes formed by a third-generation cephalosporin, ceftriaxone (H3cef), were
      studied by spectroscopic (EPR, electron paramagnetic resonance), pH
      potentiometric and computational (DFT, density functional theory) methods. The
      behavior of the model systems containing 6-hydroxy-2-methyl-3-thioxo-3,4-dihydro
      1,2,4-triazine-5(2H)-one (H2hmtdt) and 3-benzylthio-6-hydroxy-2-methyl-1,2,4
      triazine-5(2H)-one (Hbhmt) was examined for comparison. The stability of the
      tautomers of ceftriaxone and 6-hydroxy-2-methyl-3-thioxo-3,4-dihydro-1,2,4
      triazine-5(2H)-one in the neutral, mono- and bi-anionic form was calculated by
      DFT methods, both in the gas phase and in aqueous solution, and the electron
      density on the oxygen atoms of the hydroxytriazinone ring was related to the pKa
      of the ligands. The data demonstrate that ceftriaxone coordinates V(IV)O(2+)
      forming mono- and bis-chelated complexes with (Oket, O(-)) donor set and
      formation of five-membered chelate rings. The geometry of the bis-chelated
      complex, cis-[VO(Hcef)2(H2O)](2-), is cis-octahedral and this species can
      deprotonate, around physiological pH, to form the corresponding mono-hydroxido
      cis-[VO(Hcef)2(OH)](3-). The interaction of cis-[VO(Hcef)2(H2O)](2-) with apo
      transferrin (apo-hTf) was studied and the results suggest that V(IV)O(2+)
      distributes between (VO)apo-hTf/(VO)2apo-hTf and cis-[VO(Hcef)2(H2O)](2-),
      whereas mixed complexes are not formed for charge and steric effects. The
      interaction of cis-[VO(Hcef)2(H2O)](2-) with red blood cells shows that
      ceftriaxone helps V(IV)O(2+) ion to cross the erythrocyte membrane. Inside the
      cell cis-[VO(Hcef)2(H2O)](2-) decomposes and the same species formed by inorganic
      V(IV)O(2+) are observed. The relationship between the biotransformation in the
      plasma and red blood cells and the potential pharmacological activity of
      V(IV)O(2+) species of ceftriaxone is finally discussed. 

PMID- 25601643
TI  - Nongenetic inheritance and transgenerational epigenetics.
AB  - The idea that inherited genotypes define phenotypes has been paramount in modern
      biology. The question remains, however, whether stable phenotypes could be also
      inherited from parents independently of the genetic sequence per se. Recent data
      suggest that parental experiences can be transmitted behaviorally, through in
      utero exposure of the developing fetus to the maternal environment, or through
      either the male or female germline. The challenge is to delineate a plausible
      mechanism. In the past decade it has been proposed that epigenetic mechanisms are
      involved in multigenerational transmission of phenotypes and transgenerational
      inheritance. The prospect that ancestral experiences are written in our epigenome
      has immense implications for our understanding of human behavior, health, and
      disease. 

PMID- 25601644
TI  - Accommodating family life: mentoring future female faculty members.
AB  - The demands of family life are crucial factors in successfully retaining women in
      science. Retention efforts should focus on creating a family-friendly environment
      within the laboratory and the institute. Based on my own experiences, I suggest
      ways to attract top young scientists and support their development into leading
      researchers. 

PMID- 25601645
TI  - Persistence of psychotic symptoms as an indicator of cognitive impairment in
      methamphetamine users.
AB  - BACKGROUND: Prolonged exposure to methamphetamine (meth) has neurotoxic effects
      and impairs neurocognitive functions. This study aims to ascertain whether meth
      users who experience persistent psychosis suffer more severe cognitive impairment
      than those not experiencing persistent psychosis. METHODS: This cross-sectional
      study includes 252 participants: 25 meth users without psychosis (METH-P), 50
      with brief psychosis (METH+BP), and 56 with persistent psychosis (METH+PP), as
      well as 54 patients with schizophrenia and 67 healthy controls. The
      neurocognitive function and clinical psychopathology of each patient were
      evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the
      Brief Psychiatric Rating Scale (BPRS), respectively. RESULTS: All cognitive
      domains evaluated with BACS (verbal memory, working memory, motor speed, verbal
      fluency, attention and processing speed, executive function, and composite
      scores) in METH+PP patients were similar to those in the schizophrenia patients
      and were worse than those in METH-P, METH+BP, and the healthy control subjects.
      Furthermore, cognitive functioning in meth users that did not experience
      persistent psychosis showed no statistically significant difference compared with
      the healthy control subjects. Among the meth users in this study, the negative
      symptom scores in the BPRS correlated to cognitive performance on the BACS, with
      the exception of motor speed. CONCLUSIONS: Meth users display heterogeneity in
      their psychotic symptoms and cognitive profiles. Therefore, persistent psychotic
      symptoms may denote a risk for cognitive decline among meth users. Further
      longitudinal studies should be performed in the future to clarify the causal
      relationship between cognitive deficits and the development of persistent
      psychosis.

PMID- 25601646
TI  - Letter by Wang regarding article, "efficacy and safety of catheter-based
      radiofrequency renal denervation in stented renal arteries".

PMID- 25601647
TI  - Low signal quality pulse oximetry measurements in newborn infants are reliable
      for oxygen saturation but underestimate heart rate.
AB  - AIM: We assessed the influence of system messages (SyMs) on oxygen saturation
      (SpO2 ) and heart rate measurements after birth to see whether clinical decision
      making changed if clinicians included SyM data. METHODS: The heart rate and SpO2
      of term infants were recorded using Masimo pulse oximeters. Differences in means
      and standard deviations (SD) were calculated. Permutation corrected the nonrandom
      distribution and intersubject variation. SpO2 and heart rate centile charts were
      computed with, and without, SyMs. RESULTS: Pulse oximetry measurements from 117
      neonates provided 28 477 data points. SyMs occurred in 46% of measurements. Low
      signal quality accounted for 99.9% of SyMs. The mean SpO2 was lower with SyMs (p
      < 0.001), while the SpO2 SD was similar to data without SyMs. The SpO2 centile
      charts were approximately 2% lower with SyMs included, but they were not more
      dispersed. Mean heart rate was lower (p < 0.001) and more dispersed (p < 0.001)
      when a SyM occurred. The heart rate centile charts were lower, with increased
      variability, when SyMs were included. CONCLUSION: A SyM occurred frequently
      during pulse oximetry in term infants after birth. SpO2 measurements with low
      signal quality proved reliable for monitoring an infant's clinical condition.
      However, heart rate could be underestimated by low signal quality measurements.

PMID- 25601648
TI  - Control of orbital reconstruction in (LaAlO3)M/(SrTiO3)N(001) quantum wells by
      strain and confinement.
AB  - The diverse functionality emerging at oxide interfaces calls for a fundamental
      understanding of the mechanisms and control parameters of electronic
      reconstructions. Here, we explore the evolution of electronic phases in
      (LaAlO3)M/(SrTiO3)N (001) superlattices as a function of strain and confinement
      of the SrTiO3 quantum well. Density functional theory calculations including a
      Hubbard U term reveal a charge ordered Ti(3+) and Ti(4+) state for N = 2 with an
      unanticipated orbital reconstruction, displaying alternating d(xz) and d(yz)
      character at the Ti(3+) sites, unlike the previously reported d(xy) state,
      obtained only for reduced c-parameter at a(STO). At aLAO c-compression leads to a
      Dimer-Mott insulator with alternating d(xz), d(yz) sites and an almost zero band
      gap. Beyond a critical thickness of N = 3 (a(STO)) and N = 4 (aLAO) an insulator
      to-metal transition takes place, where the extra e/2 electron at the interface is
      redistributed throughout the STO slab with a d(xy) interface orbital occupation
      and a mixed d(xz) + d(yz) occupation in the inner layers. Chemical variation of
      the SrTiO3 counterpart (LaAlO3 vs. NdGaO3) proves that the significant octahedral
      tilts and distortions in the SrTiO3 quantum well are induced primarily by the
      electrostatic doping at the polar interface and not by variation of the SrTiO3
      counterpart.

PMID- 25601649
TI  - TRIB3 mediates the expression of Wnt5a and activation of nuclear factor-kappaB in
      Porphyromonas endodontalis lipopolysaccharide-treated osteoblasts.
AB  - Porphyromonas endodontalis lipopolysaccharide (LPS) is considered to be
      correlated with the progression of bone resorption in periodontal and periapical
      diseases. Wnt5a has recently been implicated in inflammatory processes, but its
      role is unclear as a P. endodontalis LPS-induced mediator in osteoblasts.
      Tribbles homolog 3 (TRIB3) encodes a pseudokinase and has been linked to
      inflammation in certain situations. Here, we found that P. endodontalis LPS
      induced Wnt5a expression in a dose- and time-dependent manner and it also
      upregulated translocation, phosphorylation and transcriptional activity of
      nuclear factor-kappaB (NF-kappaB) in MC3T3-E1 cells. Bay 11-7082 blocked the
      translocation of NF-kappaB and Wnt5a expression induced by P. endodontalis LPS.
      Chromatin immunoprecipitation assay further established that induction of Wnt5a
      by P. endodontalis LPS was mediated through the NF-kappaB p65 subunit.
      Additionally, P. endodontalis LPS increased expression of TRIB3 in osteoblasts
      after 10 h simulated time. Overexpression of TRIB3 enhanced NF-kappaB
      phosphorylation and Wnt5a induction, whereas knockdown of TRIB3 inhibited NF
      kappaB phosphorylation and Wnt5a expression in P. endodontalis LPS-stimulated
      osteoblasts. These results suggest that P. endodontalis LPS has the ability to
      promote the expression of Wnt5a in mouse osteoblasts, and this induction is
      mainly mediated by NF-kappaB pathway. TRIB3 seems to modulate the sustained
      expression of Wnt5a in osteoblasts stimulated by P. endodontalis LPS, as well as
      regulating NF-kappaB phosphorylation.

PMID- 25601650
TI  - Dynamic properties of excitons in ZnO/AlGaN/GaN hybrid nanostructures.
AB  - Hybrid samples based on ZnO colloidal nanocrystals (NCs) deposited on AlGaN/GaN
      quantum well (QW) structures with different top barrier thickness d = 3, 6 and 9
      nm are studied by time-resolved photoluminescence. Thermal behavior of the QW
      exciton lifetime in the hybrids and in the bare QW structures has been compared
      and it has been found that the QW exciton recombination rate increases in the
      hybrid having d = 3 nm and decreases in the hybrid with d = 6 nm, while no change
      has been observed for the structure with d = 9 nm. It is suggested that non
      radiative resonance energy transfer from the QW excitons to the ZnO NCs and a
      variation of the surface potential can both influence the QW exciton lifetime in
      the hybrids.

PMID- 25601652
TI  - VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors.
AB  - Immune escape is a prerequisite for tumor development. To avoid the immune
      system, tumors develop different mechanisms, including T cell exhaustion, which
      is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA
      4, Tim-3, and a progressive loss of function. The recent development of therapies
      targeting PD-1 and CTLA-4 have raised great interest since they induced long
      lasting objective responses in patients suffering from advanced metastatic
      tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is
      unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key
      role in the development of an immunosuppressive microenvironment. We report in
      the present work that VEGF-A produced in the tumor microenvironment enhances
      expression of PD-1 and other inhibitory checkpoints involved in CD8(+) T cell
      exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A
      VEGFR. In view of these results, association of anti-angiogenic molecules with
      immunomodulators of inhibitory checkpoints may be of particular interest in VEGF
      A-producing tumors. 

PMID- 25601654
TI  - The influence of hemostatic agents on bone healing after sternotomy in a porcine
      model.
AB  - BACKGROUND: Sternotomy is the preferred access to the mediastinum. During
      sternotomy, trabecular bone is exposed, often resulting in bleeding, which can be
      treated with mechanical hemostatic agents; however, their influence on the
      healing process is relatively unexplored. The aim of this study was to
      investigate the influence of two hemostatic agents: bone wax (BW) and a water
      soluble polymer wax, Ostene (WSW), on the mechanical and histologic
      characteristics of healing sternal bone. METHODS: Twenty-four pigs underwent
      sternotomy and were randomized into three groups: WSW, BW, or no hemostatic
      treatment (control). Bone samples were obtained 6 weeks postoperatively. RESULTS:
      Fracture strength (Fmax) and maximum stiffness (dF/dx) was lower in the BW group
      than in controls (Fmax: 175.2 vs. 255.8 N, dF/dx: 165.2 vs. 375.4 N/mm,) (p <
      0.05). The stiffness did not differ statistically between the WSW and BW groups
      (298.4 vs 165.2 N/mm) nor did the fracture strength (211.4 vs 175.2 N). The
      fraction of granulomatous tissue was higher in the BW group compared with both
      the WSW group (79.1 vs. 16.52%) (p < 0.001) and controls (79.1 vs. 11.2%) (p <
      0.001). There was more calcified tissue in controls than in the BW group (23.4
      vs. 10.8%) (p < 0.05). CONCLUSIONS: In a porcine model, BW significantly
      inhibited sternal healing and was associated with chronic inflammation and
      reduced mechanical integrity. The WSW did not, to the same degree as BW, inhibit
      bone healing and thus presents an alternative treatment option for sternal
      bleeding.

PMID- 25601651
TI  - Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic
      gradient.
AB  - Neutrophils respond to invading bacteria by adopting a polarized morphology,
      migrating in the correct direction, and engulfing the bacteria. How neutrophils
      establish and precisely orient this polarity toward pathogens remains unclear.
      Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin)
      protein moesin in its active form (phosphorylated and membrane bound) prevented
      cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. Attractant
      induced activation of myosin phosphatase deactivated moesin at the prospective
      leading edge to break symmetry and establish polarity. Subsequent translocation
      of moesin to the trailing edge confined the formation of a prominent pseudopod
      directed toward pathogens and prevented secondary pseudopod formation in other
      directions. Therefore, both moesin-mediated inhibition and its localized
      deactivation by myosin phosphatase are essential for neutrophil polarization and
      effective neutrophil tracking of pathogens. 

PMID- 25601655
TI  - Acute degradation of the endothelial glycocalyx in infants undergoing cardiac
      surgical procedures.
AB  - BACKGROUND: There is no doubt today about the existence of the endothelial
      glycocalyx (EG) and its decisive role in maintaining vascular homeostasis in
      adult humans. Shedding of the EG has been demonstrated in adults with sepsis or
      trauma, in patients undergoing major operations, and after ischemia/reperfusion.
      The aim of the present study was to demonstrate whether shedding of the EG also
      occurs in infants undergoing heart operations. METHODS: Two major constituents of
      the EG (syndecan-1 and hyaluronan) were measured in the arterial serum of 42
      infants during cardiac operations in a prospective observational study. The
      groups were defined according to the ischemic impact: cardiac operations with
      cardiopulmonary bypass under beating heart conditions (CPB group, regional
      ischemia of lungs, n = 10), operations with cardiopulmonary bypass and aortic
      clamping (CPB+AC group, regional ischemia of heart and lungs, n = 24), and
      cardiac operations with deep hypothermic circulatory arrest (CPB+AC+DHCA group,
      whole-body ischemia, n = 8). RESULTS: Syndecan-1 and hyaluronan were detected in
      all infants, providing an indication for the presence of a glycocalyx. During the
      operations, no significant difference in syndecan-1 concentration was observed in
      the CPB group, but levels increased significantly in both other groups (maximum
      increases: CPB+AC 3.0-fold, CPB+AC+DHCA 3.7-fold, p < 0.05). Hyaluronan increased
      significantly in the course of the operation in all groups (maximum increases:
      CPB 1.2-fold, CPB+AC 1.4-fold, CPB+AC+DHCA 1.7-fold, p < 0.05). CONCLUSIONS: The
      present data provides the first evidence for basal turnover of vascular EG in
      infants. Similarly to the process in adults, the shedding of this structure
      increases with ischemia/reperfusion, the extent being dependent on the degree of
      ischemic challenge.

PMID- 25601656
TI  - Physical activity in school-age children born preterm.
AB  - OBJECTIVES: To compare objectively measured physical activity in 11- and 15-year
      old children who were born preterm with term-born controls and related physical
      activity measures to lung function measures. STUDY DESIGN: We used data from the
      Avon Longitudinal Study of Parents and Children. We compared total physical
      activity, moderate-to-vigorous physical activity, and sedentary behavior between
      children born at 25-32, 33-34, 35-36, and 37-43 weeks' gestation at ages 11 and
      15 years. At age 11 years, physical activity measures were correlated with lung
      spirometry recorded at age 7-9 years. RESULTS: Valid physical activity data at
      age 11 years were available for 5025, 197, 57, and 48 children born at 37-43, 35
      36, 33-34, and 25-32 weeks' gestation, respectively. At age 15 years, valid
      physical activity data were available for 1829, 62, 32, and 24 children born at
      37-43, 35-36, 33-34, and 25-32 weeks' gestation. Boys were more physically active
      than girls at both ages. There were no differences in total physical activity,
      moderate-to-vigorous physical activity, or sedentary behavior in children between
      the different gestation groups. Physical activity at age 11 years did not
      correlate with spirometry measures at age 7-9 years. CONCLUSIONS: Physical
      activity was similar for the different gestational groups and did not correlate
      with lung spirometry. Physical activity does not appear to be limited in preterm
      born children despite lung function deficits noted in childhood.

PMID- 25601657
TI  - Open saphenous vein harvest.

PMID- 25601653
TI  - Defective lymphoid organogenesis underlies the immune deficiency caused by a
      heterozygous S32I mutation in IkappaBalpha.
AB  - Patients with ectodermal dysplasia with immunodeficiency (ED-ID) caused by
      mutations in the inhibitor of NF-kappaB alpha (IkappaBalpha) are susceptible to
      severe recurrent infections, despite normal T and B cell numbers and intact in
      vitro lymphocyte function. Moreover, the outcome of hematopoietic stem cell
      transplantation (HSCT) in these patients is poor despite good engraftment. Mice
      heterozygous for the IkappaBalpha S32I mutation found in patients exhibited
      typical features of ED-ID. Strikingly, the mice lacked lymph nodes, Peyer's
      patches, splenic marginal zones, and follicular dendritic cells and failed to
      develop contact hypersensitivity (CHS) or form germinal centers (GCs), all
      features not previously recognized in patients and typical of defective
      noncanonical NF-kappaB signaling. Lymphotoxin beta receptor (LTbetaR)-driven
      induction of chemokines and adhesion molecules mediated by both canonical and
      noncanonical NF-kappaB pathways was impaired, and levels of p100 were markedly
      diminished in the mutant. IkappaBalpha mutant -> Rag2(-/-), but not WT
      >IkappaBalpha mutant, bone marrow chimeras formed proper lymphoid organs and
      developed CHS and GCs. Defective architectural cell function explains the
      immunodeficiency and poor outcome of HSCT in patients with IkappaBalpha
      deficiency and suggests that correction of this niche is critical for
      reconstituting their immune function.

PMID- 25601658
TI  - Development of a time sensitivity score for frequently occurring motor vehicle
      crash injuries.
AB  - BACKGROUND: Injury severity alone is a poor indicator of the time sensitivity of
      injuries. The purpose of the study was to quantify the urgency with which the
      most frequent motor vehicle crash injuries require treatment, according to expert
      physicians. STUDY DESIGN: The time sensitivity was quantified for the top 95%
      most frequently occurring Abbreviated Injury Scale (AIS) 2+ injuries in the
      National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) 2000
      2011. A Time Sensitivity Score was developed using expert physician survey data
      in which physicians were asked to determine whether a particular injury should go
      to a Level I/II trauma center and the urgency with which that injury required
      treatment. RESULTS: When stratifying by AIS severity, the mean Time Sensitivity
      Score increased with increasing AIS severity. The mean Time Sensitivity Scores by
      AIS severity were as follows: 0.50 (AIS 2); 0.78 (AIS 3); 0.92 (AIS 4); 0.97 (AIS
      5); and 0.97 (AIS 6). When stratifying by anatomical region, the head, thorax,
      and abdomen were the most time sensitive. CONCLUSIONS: Appropriate triage depends
      on multiple factors, including the severity of an injury, the urgency with which
      it requires treatment, and the propensity of a significant injury to be missed.
      The Time Sensitivity Score did not correlate highly with the widely used AIS
      severity scores, which highlights the inability of AIS scores to capture all
      aspects of injury severity. The Time Sensitivity Score can be useful in Advanced
      Automatic Crash Notification systems for identifying highly time sensitive
      injuries in motor vehicle crashes requiring prompt treatment at a trauma center.

PMID- 25601660
TI  - Winning the colonoscopy revaluation delay.

PMID- 25601659
TI  - Comprehensive bioimaging with fluorinated nanoparticles using breathable liquids.
AB  - Fluorocarbons are lipophobic and non-polar molecules that exhibit remarkable
      biocompatibility, with applications in liquid ventilation and synthetic blood.
      The unique properties of these compounds have also enabled mass spectrometry
      imaging of tissues where the fluorocarbons act as a Teflon-like coating for
      nanostructured surfaces to assist in desorption/ionization. Here we report
      fluorinated gold nanoparticles (f-AuNPs) designed to facilitate nanostructure
      imaging mass spectrometry. Irradiation of f-AuNPs results in the release of the
      fluorocarbon ligands providing a driving force for analyte desorption. The f
      AuNPs allow for the mass spectrometry analysis of both lipophilic and polar
      (central carbon) metabolites. An important property of AuNPs is that they also
      act as contrast agents for X-ray microtomography and electron microscopy, a
      feature we have exploited by infusing f-AuNPs into tissue via fluorocarbon
      liquids to facilitate multimodal (molecular and anatomical) imaging. 

PMID- 25601661
TI  - Gastrointestinal bleeding. Gastrointestinal bleeding risk is increased by novel
      anticoagulants.
AB  - A report has demonstrated that in patients with atrial fibrillation the novel
      oral anticoagulant, dabigatran, increases the risk of gastrointestinal bleeding
      by nearly twofold compared with warfarin. Here, the risk of gastrointestinal
      bleeding associated with anticoagulants and antiplatelet agents is placed into
      clinical context and key management principles are emphasized.

PMID- 25601667
TI  - IBD: Strategic management of postoperative Crohn's disease.

PMID- 25601668
TI  - Pancreatic cancer: From normal to metastases--a whole gamut of pancreatic
      organoids.

PMID- 25601664
TI  - The concept of gut rehabilitation and the future of visceral transplantation.
AB  - In the 1990s, the introduction of visceral transplantation fuelled interest in
      other innovative therapeutic modalities for gut rehabilitation. Ethanol lock and
      omega-3 lipid formulations were introduced to reduce the risks associated with
      total parenteral nutrition (TPN). Autologous surgical reconstruction and bowel
      lengthening have been increasingly utilized for patients with complex abdominal
      pathology and short-bowel syndrome. Glucagon-like peptide 2 analogue, along with
      growth hormone, are available to enhance gut adaptation and achieve nutritional
      autonomy. Intestinal transplantation continues to be limited to a rescue therapy
      for patients with TPN failure. Nonetheless, survival outcomes have substantially
      improved with advances in surgical techniques, immunosuppressive strategies and
      postoperative management. Furthermore, both nutritional autonomy and quality of
      life can be restored for more than two decades in most survivors, with social
      support and inclusion of the liver being favourable predictors of long-term
      outcome. One of the current challenges is the discovery of biomarkers to diagnose
      early rejection and further improve liver-free allograft survival. Currently,
      chronic rejection with persistence of preformed and development of de novo donor
      specific antibodies is a major barrier to long-term graft function; this issue
      might be overcome with innovative immunological and tolerogenic strategies. This
      Review discusses advances in the field of gut rehabilitation, including
      intestinal transplantation, and highlights future challenges. With the growing
      interest in individualized medicine and the value of health care, a novel
      management algorithm is proposed to optimize patient care through an integrated
      multidisciplinary team approach. 

PMID- 25601670
TI  - Mechanical failure of metal-polyethylene sandwich liner in metal-on-metal total
      hip replacement.
AB  - Metal-on-metal had been proposed as an optimal articulation in THRs, however,
      many monoblock prostheses have been recalled in the USA because of significant
      high rates of early failure. Metal-on-metal prostheses had been implanted in our
      institution, and this is a case history of a single patient, in whom metal-on
      metal THRs with different femoral sizes of heads were implanted. A 57-year-old
      female patient underwent bilateral total hip replacements with metal-on-metal
      prostheses using metal-polyethylene "sandwich" liners 9 years ago on the right
      side and 7 years ago on the left side respectively. The only difference in both
      sides was the femoral head diameter of 28 mm in right and 34 mm in left. Seven
      years after the left surgery, the acetabular liner was dissociated, however,
      metallosis was not detected. Although the larger femoral head was thought to
      increase hip joint stability, it dictated a reduction in polyethylene thickness
      in this prosthesis design, and it was 4 mm in the left hip. Recently, metal-on
      metal articulations are thought not to be optimal for hip joint bearing surface,
      however, this clinical failure was due to the polyethylene thickness and quality.

PMID- 25601669
TI  - Ultrasonic mediated synthesis of monodispersed lanthanum hydroxide nanorods for
      possible bioimplant application.
AB  - Monodispersed lanthanum hydroxide nano-rods (LaNRs) were synthesized for
      prospective biomedical application using a microwave heating and ultrasonic
      agitation methodology which does not require any toxic stabilizing agent. The
      average length and diameter of the LaNRs thus obtained were 183.4 +/- 3.6 and 9.9
      +/- 0.2 nm respectively, as analyzed by HRTEM. FTIR spectrum confirmed the
      presence of OH groups. The thermal transformation of lanthanum hydroxide
      (La(OH)3) was studied by thermogravimetric analysis. The synthesized LaNRs were
      found to be stable for a period of 1 month at room temperature. They were
      biocompatible as evaluated by haemocompatibility assay and viability assay using
      human peripheral blood mononuclear cells. The pro-angiogenic property of LaNRs
      was demonstrated by in vivo chick chorioallantoic membrane assay. The LaNRs
      induced osteoblast differentiation of human adipose derived stem cells with
      significant calcium (Ca(2+)) deposition indicating potential applications in bone
      tissue engineering.

PMID- 25601673
TI  - A critique on the structural analysis of lignins and application of novel tandem
      mass spectrometric strategies to determine lignin sequencing.
AB  - This review is devoted to the application of MS using soft ionization methods
      with a special emphasis on electrospray ionization, atmospheric pressure
      photoionization and matrix-assisted laser desorption/ionization MS and tandem MS
      (MS/MS) for the elucidation of the chemical structure of native and modified
      lignins. We describe and critically evaluate how these soft ionization methods
      have contributed to the present-day knowledge of the structure of lignins.
      Herein, we will introduce new nomenclature concerning the chemical state of
      lignins, namely, virgin released lignins (VRLs) and processed modified lignins
      (PML). VRLs are obtained by liberation of lignins through degradation of
      vegetable matter by either chemical hydrolysis and/or enzymatic hydrolysis. PMLs
      are produced by subjecting the VRL to a series of further chemical
      transformations and purifications that are likely to alter their original
      chemical structures. We are proposing that native lignin polymers, present in the
      lignocellulosic biomass, are not made of macromolecules linked to cellulose
      fibres as has been frequently reported. Instead, we propose that the lignins are
      composed of vast series of linear related oligomers, having different lengths
      that are covalently linked in a criss-cross pattern to cellulose and
      hemicellulose fibres forming the network of vegetal matter. Consequently,
      structural elucidation of VRLs, which presumably have not been purified and
      processed by any other type of additional chemical treatment and purification,
      may reflect the structure of the native lignin. In this review, we present an
      introduction to a MS/MS top-down concept of lignin sequencing and how this
      technique may be used to address the challenge of characterizing the structure of
      VRLs. Finally, we offer the case that although lignins have been reported to have
      very high or high molecular weights, they might not exist on the basis that such
      polymers have never been identified by the mild ionizing techniques used in
      modern MS.

PMID- 25601674
TI  - In ESI-source H/D exchange under atmospheric pressure for peptides and proteins
      of different molecular weights from 1 to 66 kDa: the role of the temperature of
      the desolvating capillary on H/D exchange.
AB  - Transition of proteins from the solution to the gas phase during electrospray
      ionization remains a challenging problem despite the large amount of attention it
      has received during the past few decades. One of the major questions relates to
      the extent to which proteins in the gas phase retain their condensed phase
      structures. We have used in-electrospray source hydrogen/deuterium exchange to
      determine the number of deuterium incorporations as a function of protein mass,
      charge state and temperature of the desolvating capillary where the reaction
      occurs. All experiments were performed on a Thermo LTQ FT Ultra equipped with a 7
      T superconducting magnet. Ions were generated by an IonMax Electrospray ion
      source operated in the positive ESI mode. Deuterium exchange was performed by
      introducing a droplet of D2 O beneath the ESI capillary. We systematically
      investigated gas phase hydrogen/deuterium (H/D) exchange under atmospheric
      pressure for peptides and proteins of different molecular weights from 1 to 66
      kDa. We observed that almost all proteins demonstrate similar exchange rates for
      all charge states and that these rates increase exponentially with the
      temperature of the desolvating capillary. We did not observe any clear
      correlation of the number of H/D exchanges with the value of the cross section
      for a corresponding charge state. We have demonstrated the possibility of
      performing in-ESI source H/D exchange of large proteins under atmospheric
      pressure. The simplicity of the experimental setup makes it a useful experimental
      technique that can be applied for the investigation of gas phase conformations of
      proteins.

PMID- 25601671
TI  - Electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) for
      endothelial cell growth.
AB  - Electrospun scaffolds of silk fibroin (SF) and poly(lactide-co-glycolide) (PLGA)
      were prepared to mimic the morphology and chemistry of the extracellular matrix.
      The SF/PLGA scaffolds were treated with ethanol to improve their usability. After
      ethanol treatment the scaffolds exhibited a smooth surface and uniform fibers. SF
      transformed from random coil conformation to beta-sheet structure after ethanol
      treatment, so that the SF/PLGA scaffolds showed low hydrophilicity and dissolving
      rate in water. The mechanical properties and the hydrophilicity of the blended
      fibrous scaffolds were affected by the weight ratio of SF and PLGA. During
      degradation of ethanol-treated SF/PLGA scaffolds in vitro, the fibers became thin
      along with the degradation time. Human umbilical vein endothelial cells (HUVECs)
      were seeded onto the ethanol-treated nanofibrous scaffolds for cell viability,
      attachment and morphogenesis studies. These SF/PLGA scaffolds could enhance the
      viability, spreading and attachment of HUVECs. Based on these results, these
      ethanol-treated scaffolds are proposed to be a good candidate for endothelial
      cell growth. 

PMID- 25601675
TI  - Volatile compound changes during shelf life of dried Boletus edulis: comparison
      between SPME-GC-MS and PTR-ToF-MS analysis.
AB  - Drying process is commonly used to allow long time storage of valuable porcini
      mushrooms (Boletus edulis). Although considered a stable product dried porcini
      flavour changes during storage. Monitoring of volatile compounds during shelf
      life may help to understand the nature of the observed changes. In the present
      work two mass spectrometric techniques were used to monitor the evolution of
      volatile compounds during commercial shelf life of dried porcini. Solid phase
      microextraction (SPME) coupled to gas chromatography - mass spectrometry (GC-MS)
      allowed the identification of 66 volatile compounds, 36 of which reported for the
      first time, monitored during the commercial shelf life of dried porcini. Proton
      transfer reaction - time of flight - mass spectrometry (PTR-ToF-MS) , a direct
      injection mass spectrometric technique, was shown to be a fast and sensitive
      instrument for the general monitoring of volatile compound evolution during
      storage of dried porcini. Furthermore, PTR-ToF-MS grants access to compounds
      whose determination would otherwise require lengthy pre-concentration and/or
      derivatization steps such as ammonia and small volatile amines. The two
      techniques, both used for the first time to study dried porcini, provided
      detailed description of time evolution of volatile compounds during shelf life.
      Alcohols, aldehydes, ketones and monoterpenes diminish during the storage while
      carboxylic acids, pyrazines, lactones and amines increase. The storage
      temperature modifies the rate of the observed changes influencing the final
      quality of the dried porcini. We showed the advantages of both techniques,
      suggesting a strategy to be adopted to follow time evolution of volatile
      compounds in food products during shelf life, based on the identification of
      compounds by GC-MS and the rapid time monitoring by PTR-ToF-MS measurements in
      order to maximize the advantages of both techniques.

PMID- 25601676
TI  - Atmospheric pressure laser desorption/ionization using a 6-7 um-band mid-infrared
      tunable laser and liquid water matrix.
AB  - Due to the characteristic absorption peaks in the IR region, various molecules
      can be used as a matrix for infrared matrix-assisted laser desorption/ionization
      (IR-MALDI). Especially in the 6-7 um-band IR region, solvents used as the mobile
      phase for liquid chromatography have absorption peaks that correspond to their
      functional groups, such as O-H, C=O, and CH3. Additionally, atmospheric pressure
      (AP) IR-MALDI, which is applicable to liquid-state samples, is a promising
      technique to directly analyze untreated samples. Herein we perform AP-IR-MALDI
      mass spectrometry of a peptide, angiotensin II, using a mid-IR tunable laser with
      a tunable wavelength range of 5.50-10.00 um and several different matrices. The
      wavelength dependences of the ion signal intensity of [M + H](+) of the peptide
      are measured using a conventional solid matrix, alpha-cyano-4-hydroxycinnamic
      acid (CHCA) and a liquid matrix composed of CHCA and 3-aminoquinoline. Other than
      the O-H stretching and bending vibration modes, the characteristic absorption
      peaks are useful for AP-IR-MALDI. Peptide ions are also observed from an aqueous
      solution of the peptide without an additional matrix, and the highest peak
      intensity of [M + H](+) is at 6.00 um, which is somewhat shorter than the
      absorption peak wavelength of liquid water corresponding to the O-H bending
      vibration mode. Moreover, long-lasting and stable ion signals are obtained from
      the aqueous solution. AP-IR-MALDI using a 6-7 um-band IR tunable laser and
      solvents as the matrix may provide a novel on-line interface between liquid
      chromatography and mass spectrometry.

PMID- 25601677
TI  - Mass spectrometric profiling of flavonoid glycoconjugates possessing isomeric
      aglycones.
AB  - In fields such as food and nutrition science or plant physiology, interest in
      untargeted profiling of flavonoids continues to expand. The group of flavonoids
      encompasses several thousands of chemically distinguishable compounds, among
      which are a number of isobaric compounds with the same elemental composition.
      Thus, the mass spectrometric identification of these compounds is challenging,
      especially when reference standards are not available to support their
      identification. Many different types of isomers of flavonoid glycoconjugates are
      known, i.e. compounds that differ in their glycosylation position, glycan
      sequence or type of interglycosidic linkage. This work focuses on the mass
      spectrometric identification of flavonoid glycoconjugate isomers possessing the
      same glycan mass and differing only in their aglycone core. A non-targeted HPLC
      ESI-MS/MS profiling method using a triple quadrupole MS is presented herein,
      which utilizes in-source fragmentation and a pseudo-MS(3) approach for the
      selective analysis of flavonoid glycoconjugates with isomeric/isobaric aglycones.
      A selective MRM-based identification of the in-source formed isobaric aglycone
      fragments was established. Additionally, utilizing the precursor scanning
      capability of the employed triple quadrupole instrument, the developed method
      enabled the determination of the molecular weight of the studied intact flavonoid
      glycoconjugate. The versatility of the method was proven with various types of
      flavonoid aglycones, i.e. anthocyanins, flavonols, flavones, flavanones and
      isoflavones, along with their representative glycoconjugates. The developed
      method was also successfully applied to a commercially available sour cherry
      sample, in which 16 different glycoconjugates of pelargonidin, genistein,
      cyanidin, kaempferol and quercetin could be tentatively identified, including a
      number of compounds containing isomeric/isobaric aglycones.

PMID- 25601678
TI  - Chlorine substitution promotes phenyl radical loss from C8-phenoxy-2'
      deoxyguanosine adducts: implications for biomarker identification from
      chlorophenol exposure.
AB  - Chlorophenols are persistent organic pollutants, which undergo peroxidase
      mediated oxidation to afford phenolic radical intermediates that react at the C8
      site of 2'-deoxyguanosine (dG) to generate oxygen-linked C8-dG adducts. Such
      adducts are expected to contribute to chlorophenol toxicity and serve as
      effective dose biomarkers for chlorophenol exposure. Electrospray ionization mass
      spectrometry (ESI-MS) was employed to study collision induced dissociation (CID)
      for a family of such phenolic O-linked C8-dG adducts. Fragmentation of the
      deprotonated nucleosides demonstrates that an unexpected homolytic cleavage of
      the ether linkage to release phenyl radicals and a nucleoside distonic ion with
      m/z 281 competes effectively with commonly observed breakage of the glycosidic
      bond to release the deprotonated nucleobase. Increased chlorination of the phenyl
      ring enhances phenyl radical loss. Density functional theory calculations
      demonstrate that Cl-substitution decreases phenyl radical stability but promotes
      homolytic breakage of the C8-phenyl bond in the C8-dG adduct. The calculations
      suggest that phenyl radical loss is driven by destabilizing steric (electrostatic
      repulsion) interactions between the ether oxygen atom and ortho-chlorines on the
      phenyl ring. The distonic ion at m/z 281 represents a unique dissociation product
      for deprotonated O-linked C8-dG adducts and may prove useful for selective
      detection of relevant biomarkers for chlorophenol exposure by tandem mass
      spectrometry using selective reaction monitoring.

PMID- 25601680
TI  - Realistic modeling of ion-neutral collisions in quadrupole ion traps.
AB  - In this study, three ion-neutral collision models have been discussed and
      compared, including the Langevin, the hard-sphere and the mixed collision models.
      With the pseudo-potential approximation, analytical expressions of ion secular
      motions with the hard-sphere and mixed collision models have been obtained for
      the first time. Through numerical simulations and theoretical calculations, it is
      found that the mixed collision model could be used as a general description of
      ion-neutral collisions under different conditions. Langevin collision model is a
      good description of low energy collisions between small ions and neutrals, while
      hard-sphere collision model could be used to describe high energy collisions
      and/or ions with higher masses (larger physical sizes). These analytical
      expressions of ion motion decay profiles enable the creation of direct
      relationships between time-domain image currents with ion collision cross
      sections.

PMID- 25601679
TI  - Changes in lipid distribution in E. coli strains in response to norfloxacin.
AB  - Bacterial resistance to antibiotics has become an increasing threat, requiring
      not only the development of new targets in drug discovery, but more importantly,
      a better understanding of cellular response. In the current study, three closely
      related Escherichia coli strains, a wild type (MG1655) and an isogenic pair
      derived from the wild type (DPB635 and DPB636) are studied following exposure to
      sub lethal concentrations of antibiotic (norfloxacin) over time. In particular,
      genotype similarities between the three strains were assessed based on the lipid
      regulation response (e.g. presence/absence and up/down regulation). Lipid
      identification was performed using direct surface probe analysis (matrix-assisted
      laser desorption/ionization, MALDI), coupled to high-resolution mass spectrometry
      (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR MS) followed
      by statistical analysis of variability and reproducibility across batches using
      internal standards. Inspection of the lipid profile showed that for the MG1655,
      DPB635 and DPB636 E. coli strains, a similar distribution of the altered lipids
      was observed after exposure to norfloxacin antibiotic (e.g. fatty acids and
      glycerol phospholipids are up and down regulated, respectively). Additionally,
      variations in the lipid distribution resemble the extent to which each strain can
      combat the antibiotic exposure. That is, the topA66 topoisomerase I mutation of
      DPB636 translates into diminished response related to antibiotic sensitivity when
      compared to MG1655 and the DPB635 strains.

PMID- 25601681
TI  - Mass spectrometry detection of minor new meridianins from the Antarctic colonial
      ascidians Aplidium falklandicum and Aplidium meridianum.
AB  - Taking into account the broad biological activities found in the meridianin
      indole alkaloids isolated to date, we have re-examined the organic extracts of an
      Antarctic collection of the tunicates Aplidium meridianum and A. falklandicum
      (Chordata: Ascidiacea) by HPLC in conjunction with a high-resolution mass
      spectrometer (HPLC-MS). A new set of analogs of meridianins A-G has been
      detected, and their structures are proposed on the basis of the molecular
      formulae identified by LC-HRMS analysis using a C18 column with a gradient of
      water/acetonitrile and an LTQ-FT-MS Orbitrap detector. Remarkably, dimers derived
      from meridianin A and from meridianin B or E were also detected. Our findings
      provide further evidence of the broad variability within the meridianin-like
      derivatives of this highly bioactive alkaloid family.

PMID- 25601682
TI  - Development and validation of a high-resolution LTQ Orbitrap MS method for the
      quantification of isoflavones in wastewater effluent.
AB  - Isoflavones and coumestranes are the most important classes of compounds among
      phytoestrogens; by binding to estrogen receptors, they mimic or modulate the
      effect on the endogenous receptors. Little information can be found in literature
      about the presence of isoflavones and coumestrol in the environment, even if it
      is known that this may have significance, being these substances classified as
      endocrine disrupting compounds. In this research, we aim to explore the
      capabilities of the LTQ Orbitrap Discovery hybrid MS in full-scan acquisition
      mode, with high resolution, to validate an analytical method for the
      quantification of nine isoflavones (genistein, genistin, glycitein, daidzein,
      daidzin, (R,S)-equol, biochanin A, formononetin and coumestrol) in wastewater
      samples. The correlation coefficients of calibration curves of the nine analyzed
      compounds were in a range of 0.996-0.999; recoveries at two different levels of
      concentration (0.05 and 0.5 ug/l) were in the range 73-98%, and the limits of
      detection ranged between 0.0014 and 0.017 ug/l, proving that this method is
      sensitive enough in comparison with other methods available in literature. This
      method has been applied for the analysis of 20 wastewater treatment plants in
      County Cork, Ireland.

PMID- 25601683
TI  - Lysine residues in the N-terminal huntingtin amphipathic alpha-helix play a key
      role in peptide aggregation.
AB  - Huntington's disease is a genetic neurodegenerative disorder caused by an
      expansion in a polyglutamine domain near the N-terminus of the huntingtin (htt)
      protein that results in the formation of protein aggregates. Here, htt aggregate
      structure has been examined using hydrogen-deuterium exchange techniques coupled
      with tandem mass spectrometry. The focus of the study is on the 17-residue N
      terminal flanking region of the peptide that has been shown to alter htt
      aggregation kinetics and morphology. A top-down sequencing strategy employing
      electron transfer dissociation is utilized to determine the location of
      accessible and protected hydrogens. In these experiments, peptides aggregate in a
      deuterium-rich solvent at neutral pH and are subsequently subjected to deuterium
      hydrogen back-exchange followed by rapid quenching, disaggregation, and tandem
      mass spectrometry analysis. Electrospray ionization of the peptide solution
      produces the [M + 5H](5+) to [M + 10H](10+) charge states and reveals the
      presence of multiple peptide sequences differing by single glutamine residues.
      The [M + 7H](7+) to [M + 9](9+) charge states corresponding to the full peptide
      are used in the electron transfer dissociation analyses. Evidence for protected
      residues is observed in the 17-residue N-terminal tract and specifically points
      to lysine residues as potentially playing a significant role in htt aggregation.

PMID- 25601684
TI  - Clustering of sulfamic acid: ESI MS and theoretical study.
AB  - Sulfamic acid has wide application in industry and has been suggested to act as
      an effective nucleation agent for the formation of aerosols and cloud particles.
      From the point of view of the role that sulfamic acid may play in aerosol
      formation, the study of its homoaggregation is important. Gas phase clustering
      study was performed for sulfamic acid H3N.SO3, (ASA), from water and methanol
      water solutions, by help of a TOF-Q spectrometer equipped with electrospray
      ionization source, in the negative-ion mode. The structure and stability of the
      (H3N.SO3)n and [(H3N.SO3)n-H](-) (n = 1-6) were studied using DFT/B3LYP/aug-cc
      pVDZ method. The ESI MS study evidenced that both singly and doubly charged
      clusters are formed when the acids are electrosprayed from water solutions; they
      may be described as [(H3N.SO3)n-zH](z-) where z = 1 or 2. The largest identified
      clusters are built of 20 monomers. The theoretical studies showed that formation
      of higher order (ASA)n aggregates in the gas phase is energetically profitable.
      In contrast with the gas phase, aqueous solution does not favor the formation of
      (ASA)n aggregates. The study led to the conclusion that the ASA clusters are
      formed in the gas phase under the experimental conditions of the mass
      spectrometer. A hypothetical mechanism concerning the formation of the doubly
      negatively charged anionic aggregates is discussed. The obtained data suggest
      that small (NH3.SO3)n aggregates may also contribute to formation of aerosols in
      heavily polluted atmospheres with relatively large NH3 concentration.

PMID- 25601685
TI  - A mass spectrometry-based method for differentiation of positional isomers of
      monosubstituted pyrazine N-oxides using metal ion complexes.
AB  - A series of 11 pairs of substituted pyrazine N-oxides, differing in the
      substituent position, were examined using electrospray ionization mass
      spectrometry (ESI-MS) in order to use spectra to assess the differentiation of
      positional isomers. For each compound, mass spectra were recorded with three
      different metal cations, namely calcium (II), copper (II) and aluminum (III),
      with characterization of the observed peaks. Differentiation between
      regioisomeric N-oxides has been achieved by comparison of the identity and
      relative intensities of the peaks originating from the adduct ions formed with
      the metal ions. Principal component analysis (PCA) has been employed to assist in
      the interpretation of the results obtained with each metal ion, exploring
      possible trends according to the nature and position of the substituent in the
      pyrazine N-oxide.

PMID- 25601686
TI  - Gas-phase copper and silver complexes with phosphorothioate and
      phosphorodithioate pesticides investigated using electrospray ionization mass
      spectrometry.
AB  - Efforts to improve agricultural productivity have led to a growing dependency on
      organophosphorus pesticides. Phosphorothioate and phosphorodithioate pesticides
      are organophosphorus pesticide subclasses with widespread application for the
      control of insects feeding on vegetables and fruits. However, even low doses of
      these pesticides can cause neurological problems in humans; thus, their
      determination and monitoring in agricultural foodstuffs is important for human
      health. Phosphorothioate and phosphorodithioate pesticides may be poorly ionized
      during electrospray, adversely affecting limits of detection. These pesticides
      can form complexes with Cu(2+) and Ag(+) , however, potentially improving
      ionization. In the present work, we used electrospray ionization/mass
      spectrometry (ESI/MS) to study fenitrothion, parathion, diazinon, and malathion
      coordination complexes with silver and copper ions. Stable 1 : 1 and 1 : 2
      metal/pesticide complexes were detected. Mass spectra acquired from pesticide
      solutions containing Ag(+) or Cu(2+) showed a significant increase in signal-to
      background ratio over those acquired from solutions containing only the
      pesticides, with Ag(+) improving detection more effectively than Cu(2+). Addition
      of Ag(+) to a pesticide solution improved the limit of detection by ten times.
      The relative affinity of each pesticide for Ag(+) was related to complex
      stability, following the order diazinon > malathion > fenitrothion > parathion.
      The formation of Ag(+)-pesticide complexes can significantly improve the
      detection of phosphorothioate and phosphorodithioate pesticides using ESI/MS. The
      technique could potentially be used in reactive desorption electrospray
      ionization/mass spectrometry to detect phosphorothioate and phosphorodithioate
      pesticides on fruit and vegetable skins.

PMID- 25601688
TI  - Laser desorption lamp ionization source for ion trap mass spectrometry.
AB  - A two-step laser desorption lamp ionization source coupled to an ion trap mass
      spectrometer (LDLI-ITMS) has been constructed and characterized. The pulsed
      infrared (IR) output of an Nd:YAG laser (1064 nm) is directed to a target inside
      a chamber evacuated to ~15 Pa causing desorption of molecules from the target's
      surface. The desorbed molecules are ionized by a vacuum ultraviolet (VUV) lamp
      (filled with xenon, major wavelength at 148 nm). The resulting ions are stored
      and detected in a three-dimensional quadrupole ion trap modified from a Finnigan
      Mat LCQ mass spectrometer operated at a pressure of >= 0.004 Pa. The limit of
      detection for desorbed coronene molecules is 1.5 pmol, which is about two orders
      of magnitude more sensitive than laser desorption laser ionization mass
      spectrometry using a fluorine excimer laser (157 nm) as the ionization source.
      The mass spectrum of four standard aromatic compounds (pyrene, coronene, rubrene
      and 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine (OPC)) shows that
      parent ions dominate. By increasing the infrared laser power, this instrument is
      capable of detecting inorganic compounds.

PMID- 25601687
TI  - New potential biomarkers for mesterolone misuse in human urine by liquid
      chromatography quadrupole time-of-flight mass spectrometry.
AB  - In this paper, mesterolone metabolic profiles were investigated carefully.
      Mesterolone was administered to one healthy male volunteer. Urinary extracts were
      analyzed by liquid chromatography quadruple time-of-flight mass spectrometry (LC
      QTOFMS) for the first time. Liquid-liquid extraction was applied to processing
      urine samples, and dilute-shoot analyses of intact metabolites were also
      presented. In LC-QTOFMS analysis, chromatographic peaks for potential metabolites
      were hunt down by using the theoretical [M-H](-) as target ions in full scan
      experiment, and their actual deprotonated ions were analyzed in targeted MS/MS
      mode. Ten metabolites including seven new sulfate and three glucuronide
      conjugates were found for mesterolone. Because of no useful fragment ion for
      structural elucidation, gas chromatography-mass spectrometry instrumentation was
      employed to obtain structural details of the trimethylsilylated phase I
      metabolite released after solvolysis. Thus, their potential structures were
      proposed particularly by a combined MS approach. All the metabolites were also
      evaluated in terms of how long they could be detected, and S1 (1alpha-methyl
      5alpha-androst-3-one-17beta-sulfate) together with S2 (1alpha-methyl-5alpha
      androst-17-one-3beta-sulfate) was detected up to 9 days after oral
      administration, which could be the new potential biomarkers for mesterolone
      misuse.

PMID- 25601689
TI  - GridMass: a fast two-dimensional feature detection method for LC/MS.
AB  - One of the initial and critical procedures for the analysis of metabolomics data
      using liquid chromatography and mass spectrometry is feature detection. Feature
      detection is the process to detect boundaries of the mass surface from raw data.
      It consists of detected abundances arranged in a two-dimensional (2D) matrix of
      mass/charge and elution time. MZmine 2 is one of the leading software
      environments that provide a full analysis pipeline for these data. However, the
      feature detection algorithms provided in MZmine 2 are based mainly on the
      analysis of one-dimension at a time. We propose GridMass, an efficient algorithm
      for 2D feature detection. The algorithm is based on landing probes across the
      chromatographic space that are moved to find local maxima providing accurate
      boundary estimations. We tested GridMass on a controlled marker experiment, on
      plasma samples, on plant fruits, and in a proteome sample. Compared with other
      algorithms, GridMass is faster and may achieve comparable or better sensitivity
      and specificity. As a proof of concept, GridMass has been implemented in Java
      under the MZmine 2 environment and is available at
      http://www.bioinformatica.mty.itesm.mx/GridMass and MASSyPup. It has also been
      submitted to the MZmine 2 developing community.

PMID- 25601691
TI  - MALDI-MS of flavonoids: a systematic investigation of ionization and in-source
      dissociation mechanisms.
AB  - Matrix assisted laser desorption ionization (MALDI) is a technique widely
      employed in the analysis of proteins and peptides, and nowadays it has also been
      applied to small molecules. There is little significant information regarding the
      in-source dissociation processes on MALDI for natural products. Twenty-six
      flavonoids (flavanones, flavones and flavonols) were analyzed by MALDI using
      different methods (with different matrices) and without matrix to comprehend the
      in-source reactions and establish good analysis methods for these compounds.
      Depending on the class, structure and the laser intensity applied, methoxylated
      flavonoid aglycones can eliminate methyl radicals (CH3) in the source, such as
      flavonols, but lithium 2,4-dihydroxybenzoate matrix suppresses the CH3
      eliminations and retro-Diels-Alder cleavages in the source. All of the flavonoid
      O-glycosides evaluated herein eliminated the sugar in source, even in the
      presence of the matrix, and its product radical ions ([M-H-sugar](-)) were
      observed in the negative mode. The flavone C-glycosides suffered intense
      dissociation, which was reduced by the addition of a matrix and the application
      of low laser intensity, mainly in the negative mode. Depending on the hydroxyl
      substituents, the [M-H-H](-) ion was observed with variable relative intensity in
      the spectra.

PMID- 25601690
TI  - Identification and separation of saxitoxins using hydrophilic interaction liquid
      chromatography coupled to traveling wave ion mobility-mass spectrometry.
AB  - The aim of this work was to develop a reliable and efficient analytical method to
      characterise and differentiate saxitoxin analogues (STX), including sulphated
      (gonyautoxins, GTX) and non-sulphated analogues. For this purpose, hydrophilic
      interaction liquid chromatography (HILIC) was used to separate sulphated
      analogues. We also resorted to ion mobility spectrometry to differentiate the STX
      analogues because this technique adds a new dimension of separation based on ion
      gas phase conformation. Positive and negative ionisation modes were used for
      gonyautoxins while positive ionisation mode was used for non-sulphated analogues.
      Subsequently, the coupling of these three complementary techniques, HILIC-IM-MS,
      permitted the separation and identification of STX analogues; isomer
      differentiation was achieved in HILIC dimension while non-sulphated analogues
      were separated in the IM-MS dimension. Additional structural characteristics
      concerning the conformation of STXs could be obtained using IM-MS measurements.
      Thus, the collision cross sections (CCS) of STXs are reported for the first time
      in the positive ionisation mode. These experimental CCSs correlated well with the
      calculated CCS values using the trajectory method.

PMID- 25601692
TI  - New clostebol metabolites in human urine by liquid chromatography time-of-flight
      tandem mass spectrometry and their application for doping control.
AB  - In this study, clostebol metabolic profiles were investigated carefully.
      Clostebol was administered to one healthy male volunteer. Urinary extracts were
      analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry
      (MS) using full scan and targeted MS/MS techniques with accurate mass measurement
      for the first time. Liquid-liquid extraction and direct injection were applied to
      processing urine samples. Chromatographic peaks for potential metabolites were
      found by using the theoretical [M-H](-) as target ion in full scan experiment,
      and their actual deprotonated ions were analyzed in targeted MS/MS mode. Fourteen
      metabolites were found for clostebol, and nine unreported metabolites (two free
      ones and seven sulfate conjugates) were identified by MS, and their potential
      structures were proposed based on fragmentation and metabolism pathways. Four
      glucuronide conjugates were also first reported. All the metabolites were
      evaluated in terms of how long they could be detected and S1 (4xi-chloro-5xi
      androst-3xi-ol-17-one-3xi-sulfate) was considered to be the long-term metabolite
      for clostebol misuse detected up to 25 days by liquid-liquid extraction and 14
      days by direct injection analysis after oral administration. Five conjugated
      metabolites (M2, M5, S2, S6 and S7) could also be the alternative biomarkers for
      clostebol misuse.

PMID- 25601693
TI  - Precise determination of nonlinear function of ion mobility for explosives and
      drugs at high electric fields for microchip FAIMS.
AB  - High-field asymmetric waveform ion mobility spectrometry (FAIMS) separates ions
      by utilizing the characteristics of nonlinear ion mobility at high and low
      electric fields. Accurate ion discrimination depends on the precise solution of
      nonlinear relationships and is essential for accurate identification of ion
      species for applications. So far, all the nonlinear relationships of ion mobility
      obtained are based at low electric fields (E/N <65 Td). Microchip FAIMS (MU
      FAIMS) with small dimensions has high electric field up to E/N = 250 Td, making
      the approximation methods and conclusions for nonlinear relationships
      inappropriate for these systems. In this paper, we deduced nonlinear functions
      based on the first principle and a general model. Furthermore we considered the
      hydrodynamics of gas flow through microchannels. We then calculated the specific
      alpha coefficients for cocaine, morphine, HMX, TNT and RDX, respectively, based
      on their FAIMS spectra measured by MU-FAIMS system at ultra-high fields up to 250
      Td. The results show that there is no difference in nonlinear alpha functions
      obtained by the approximation and new method at low field (<120 Td), but the
      error induced by using approximation method increases monotonically with the
      increase in field, and could be as much as 30% at a field of 250 Td.

PMID- 25601694
TI  - Enhanced simulation of an RF ion funnel including gas turbulence.
AB  - Electrodynamic ion funnels are used to enhance the transmission of ions in
      electrospray-based ion injection systems in 0.1 to 30 Torr pressure range. Jet
      disrupters are commonly employed to prevent droplets and high pressure jets from
      entering subsequent vacuum regions. This study presents the simulation and
      testing of an ion funnel containing a jet disrupter using computational fluid
      dynamics (CFD) and SIMION ion trajectory simulations. Traditional modeling
      approaches have utilized approximations for the bulk fluid flow fields without
      including the time-varying nature of the turbulent flow present in the system,
      thus yielding idealized results. In this study, the fluid flow fields are
      calculated using CFD. In an effort to include time dependence, a random velocity
      vector, whose magnitude is proportional to the square root of the turbulence
      kinetic energy, was calculated at each time step and added to the velocity of the
      background gas. These simulations predicted that the transmitted ion current is
      effectively modulated by the variation of the jet disrupter voltage. The addition
      of the random velocity vector produced results that closely matched the
      experiments. The simulations yielded the dependence of the transmission on the
      jet disrupter voltage, and the voltage necessary for maximum ion throughput was
      accurately predicted. In addition, the magnitude of the predicted transmission
      closely matched that of the experimental results. This modeling approach could be
      extended to similar ion transport and filtering systems in which the effects of
      turbulent fluid flow cannot be ignored.

PMID- 25601695
TI  - Structure and further fragmentation of significant [a3 + Na - H]+ ions from
      sodium-cationized peptides.
AB  - A good understanding of gas-phase fragmentation chemistry of peptides is
      important for accurate protein identification. Additional product ions obtained
      by sodiated peptides can provide useful sequence information supplementary to
      protonated peptides and improve protein identification. In this work, we first
      demonstrate that the sodiated a3 ions are abundant in the tandem mass spectra of
      sodium-cationized peptides although observations of a3 ions have rarely been
      reported in protonated peptides. Quantum chemical calculations combined with
      tandem mass spectrometry are used to investigate this phenomenon by using a model
      tetrapeptide GGAG. Our results reveal that the most stable [a3 + Na - H](+) ion
      is present as a bidentate linear structure in which the sodium cation coordinates
      to the two backbone carbonyl oxygen atoms. Due to structural inflexibility,
      further fragmentation of the [a3 + Na - H](+) ion needs to overcome several
      relatively high energetic barriers to form [b2 + Na - H](+) ion with a
      diketopiperazine structure. As a result, low abundance of [b2 + Na - H](+) ion is
      detected at relatively high collision energy. In addition, our computational data
      also indicate that the common oxazolone pathway to generate [b2 + Na - H](+) from
      the [a3 + Na - H](+) ion is unlikely. The present work provides a mechanistic
      insight into how a sodium ion affects the fragmentation behaviors of peptides.

PMID- 25601696
TI  - The role of basic residues in the fragmentation process of the lysine rich cell
      penetrating peptide TP10.
AB  - Selective cleavage effect of basic residues in the fragmentation of short
      peptides has been studied intensively. In contrast, the role of basic residues in
      the degradation of large peptides, such as cell-penetrating peptides, is largely
      unknown. In this work, the fragmentation of a 21 residues cell-penetrating
      peptide TP10 containing four lysine residues was studied by collision-induced
      dissociation mass spectrometry and computation methods. The influence of lysine
      residues on amide bond cleavage and fragmentation products was investigated. The
      results revealed that the selective cleavage effect of lysine residue did not
      present when the adjacent lysine residues in TP10 were both protonated. The
      localized high positive charge density might be the reason of preventing the
      mobile proton from migrating to the amide bonds in this part of the peptide. In
      contrast, the mobile proton preferred to reside in the N-terminal part of TP10
      which had less positive charge. This preference gave more information of the
      peptide sequence in the mass spectrometry study and was helpful for stabilizing
      the C-terminal part of TP10, in which the basic lysine residues were preserved
      and crucial to the cell-penetrating process.

PMID- 25601697
TI  - Acid-catalysed glucose dehydration in the gas phase: a mass spectrometric
      approach.
AB  - Understanding on a molecular level the acid-catalysed decomposition of the sugar
      monomers from hemicellulose and cellulose (e.g. glucose, xylose), the main
      constituent of lignocellulosic biomass is very important to increase selectivity
      and reaction yields in solution, key steps for the development of a sustainable
      renewable industry. In this work we reported a gas-phase study performed by
      electrospray triple quadrupole mass spectrometry on the dehydration mechanism of
      D-glucose. In the gas phase, reactant ions corresponding to protonated D-glucose
      were obtained in the ESI source and were allowed to undergo collisionally
      activated decomposition (CAD) into the quadrupole collision cell. The CAD mass
      spectrum of protonated D-glucose is characterized by the presence of ionic
      dehydrated daughter ion (ionic intermediates and products), which were
      structurally characterized by their fragmentation patterns. In the gas phase D
      glucose dehydration does not lead to the formation of protonated 5-hydroxymethyl
      2-furaldehyde, but to a mixed population of m/z 127 isomeric ions. To elucidate
      the D-glucose dehydration mechanism, 3-O-methyl-D-glucose was also submitted to
      the mass spectrometric study; the results suggest that the C3 hydroxyl group
      plays a key role in the reaction mechanism. Furthermore, protonated levulinic
      acid was found to be formed from the monodehydrated D-glucose ionic intermediate,
      an alternative pathway other than the known route consisting of 5-hydroxymethyl-2
      furaldehyde double hydration.

PMID- 25601698
TI  - Stability of high-mass molecular libraries: the role of the oligoporphyrin core.
AB  - Molecular beam techniques are a key to many experiments in physical chemistry and
      quantum optics. In particular, advanced matter-wave experiments with high-mass
      molecules profit from the availability of slow, neutral and mass-selected
      molecular beams that are sufficiently stable to remain intact during laser
      heating and photoionization mass spectrometry. We present experiments on the
      photostability with molecular libraries of tailored oligoporphyrins with masses
      up to 25,000 Da. We compare two fluoroalkylsulfanyl-functionalized libraries
      based on two different molecular cores that offer the same number of anchor
      points for functionalization but differ in their geometry and electronic
      properties. A pentaporphyrin core stabilizes a library of chemically well-defined
      molecules with more than 1600 atoms. They can be neutrally desorbed with
      velocities as low as 20 m/s and efficiently analyzed in photoionization mass
      spectrometry.

PMID- 25601699
TI  - Chiral differentiation of the noscapine and hydrastine stereoisomers by
      electrospray ionization tandem mass spectrometry.
AB  - Energy-dependent collision-induced dissociation (CID) of the dimers [2 M +
      Cat](+) of the noscapine and hydrastine stereoisomers was studied where Cat
      stands for Li(+), Na(+), K(+) and Cs(+) ions. These dimers were generated 'in
      situ' from the electrosprayed solution. The survival yield (SY) method was used
      for distinguishing the noscapine and hydrastine dimers. Significant differences
      were found between the characteristic collision energies (CE50, i.e. the
      collision energy necessary to obtain 50% fragmentation) of the homo- (R,R; S,S)
      and heterochiral (R,S; S,R) stereoisomers. To distinguish the enantiomer pairs L
      , D-tyrosine ([M + Tyr + Cat](+)) and L-, D-lysine ([M + Lys + Cat](+)) were used
      as chiral selectors. Furthermore, these heterodimers [M + amino acid + Cat](+)
      were also applied to determine the stereoisomeric composition. It was found that
      the characteristic collision energy (CE50) of the noscapine and hydrastine
      homodimers ([2 M + Cat](+)) was inversely proportional to the ionic radius of the
      cations. Furthermore, the structures of the dimers [2 M + Cat](+) were studied by
      high level quantum chemical calculations.

PMID- 25601700
TI  - Negative electrospray ionization mass spectrometry: a method for sequencing and
      determining linkage position in oligosaccharides from branched hemicelluloses.
AB  - Xyloglucans of apple, tomato, bilberry and tamarind were hydrolyzed by commercial
      endo beta-1-4-D-endoglucanase. The xylo-gluco-oligosaccharides (XylGos) released
      were separated on CarboPac PA 200 column in less than 15 min, and, after
      purification, they were structurally characterized by negative electrospray
      ionization mass spectrometry using a quadrupole time-of-flight (ESI-Q-TOF), a
      hybrid linear ion trap (LTQ)/Orbitrap and a hybrid quadrupole Fourier transform
      ion cyclotron resonance (FT-ICR) mass spectrometers. In order to corroborate the
      fragmentation routes observed on XylGos, some commercial galacto-manno
      oligosaccharides (GalMOs) and glucurono-xylo-oligosaccharides were also studied.
      The fragmentation pathways of the ionized GalMos were similar to those of XylGos
      ones. The product ion spectra were mainly characterized by prominent double
      cleavage (D) ions corresponding to the entire inner side chains. The directed
      fragmentation from the reducing end to the other end was observed for the main
      glycosylated backbone but also for the side-chains, allowing their complete
      sequencing. Relevant cross-ring cleavage ions from (0,2)X(j)-type revealed to be
      diagnostic of the 1-2-linked- glycosyl units from XylGos together with the 1-2
      linked glucuronic acid unit from glucuronoxylans. Resonant activation in the LTQ
      Orbitrap allowed not only determining the type of all linkages but also the O
      acetyl group location on fucosylated side-chains. Moreover, the fragmentation of
      the different side chains using the MS(n) capabilities of the LTQ/Orbitrap
      analyzer also allowed differentiating terminal arabinosyl and xylosyl
      substituents inside S and U side-chains of XylGos, respectively. The CID spectra
      obtained were very informative for distinction of isomeric structures differing
      only in their substitution pattern. These features together makes the
      fragmentation in negative ionization mode a relevant and powerful technique
      useful to highlight the subtle structural changes generally observed during the
      development of plant organs such as during fruit ripening and for the screening
      of cell wall mutants with altered hemicellulose structure.

PMID- 25601701
TI  - Differentiation of cefaclor and its delta-3 isomer by electrospray mass
      spectrometry, infrared multiple photon dissociation spectroscopy and theoretical
      calculations.

PMID- 25601702
TI  - Usnic acid and its versatility as MALDI matrix.

PMID- 25601703
TI  - A simple micro-extraction plate assay for automated LC-MS/MS analysis of human
      serum 25-hydroxyvitamin D levels.
AB  - This short application note describes a simple and automated assay for
      determination of 25-hydroxyvitamin D (25(OH)D) levels in very small volumes of
      human serum. It utilizes commercial 96-well micro-extraction plates with
      commercial 25(OH)D isotope calibration and quality control kits. Separation was
      achieved using a pentafluorophenyl liquid chromatography column followed by
      multiple reaction monitoring-based quantification on an electrospray triple
      quadrupole mass spectrometer. Emphasis was placed on providing a simple assay
      that can be rapidly established in non-specialized laboratories within days,
      without the need for laborious and time consuming sample preparation steps,
      advanced calibration or data acquisition routines. The analytical figures of
      merit obtained from this assay compared well to established assays. To
      demonstrate the applicability, the assay was applied to analysis of serum samples
      from patients with chronic liver diseases and compared to results from a routine
      clinical immunoassay.

PMID- 25601704
TI  - Improved ion optics for introduction of ions into a 9.4-T Fourier transform ion
      cyclotron resonance mass spectrometer.
AB  - Enhancements to the ion source and transfer optics of our 9.4 T Fourier transform
      ion cyclotron resonance (ICR) mass spectrometer have resulted in improved ion
      transmission efficiency for more sensitive mass measurement of complex mixtures
      at the MS and MS/MS levels. The tube lens/skimmer has been replaced by a dual ion
      funnel and the following octopole by a quadrupole for reduced ion cloud radial
      expansion before transmission into a mass-selective quadrupole. The number of
      ions that reach the ICR cell is increased by an order of magnitude for the
      funnel/quadrupole relative to the tube lens/skimmer/octopole.

PMID- 25601707
TI  - Renal transplantation in children weighing <15 kg: does concomitant lower urinary
      tract dysfunction influence the outcome?
AB  - BACKGROUND: We reviewed our experience with renal transplantation (RTx) in
      children weighing <15 kg to determine if the presence of lower urinary tract
      dysfunction (LUTD) influenced the outcome. METHODS: Between 1987 and 2012, 68 RTx
      were performed in patients weighing less than 15 kg, including 17 with associated
      LUTD and 51 without. We detailed the lower urinary tract management in these
      patients, and compared graft survival rates and estimated clearance 12 and 60
      months after RTx between groups. RESULTS: None of the patients without LUTD
      required any lower urinary tract surgery vs 8 out of 17 (47 %) with LUTD (p =
      0.0001). The latter included a temporary incontinent urinary diversion in 5 cases
      (29 %), namely 2 vesicostomies and 3 cutaneous ureterostomies. After comparable
      follow-ups, there was no difference in patient survival, graft survival, and
      glomerular filtration rates between groups. CONCLUSIONS: Provided that there is
      appropriate bladder management, a concomitant LUTD does not adversely influence
      the outcome of RTx in patients weighing less than 15 kg. However, 50 % of our
      patients required lower urinary tract reconstruction and, in 30 %, a temporary
      incontinent urinary diversion was placed at RTx, since lower urinary tract
      function could not be assessed reliably, the patient was not collaborative enough
      to be involved in a voiding program, and/or the RTx was prioritized.

PMID- 25601708
TI  - [Hypertensive choroidopathy under malignant hypertension].

PMID- 25601709
TI  - [Favorable outcome in a case of bilateral chronic ocular ischemic syndrome
      treated by emergency carotid revascularization surgery].

PMID- 25601710
TI  - [Imaging of Vogt's striae].

PMID- 25601711
TI  - [The stele of the eye doctor in the Museum of Bar and the logo of the French
      Language Society for the History of Ophthalmology].
AB  - The objectives are to: recall the circumstances of discovery of two corner
      pillars 45 years apart and other objects belonging to a circa second century
      Gallo-Roman temple; analyze the sculptures, of which the best known is the "stele
      of the eye doctor", which the French Language Society for the History of
      Ophthalmology took as inspiration for its logo; discuss the significance of
      instruments and procedures within a markedly religious context at a time when the
      mystery cults appeared; provide elements for discussion on the interpretation of
      the scenes depicted on the two pillars.

PMID- 25601713
TI  - Fascin actin bundling controls podosome turnover and disassembly while cortactin
      is involved in podosome assembly by its SH3 domain in THP-1 macrophages and
      dendritic cells.
AB  - Podosomes are dynamic degrading devices present in myeloid cells among other cell
      types. They consist of an actin core with associated regulators, surrounded by an
      adhesive ring. Both fascin and cortactin are known constituents but the role of
      fascin actin bundling is still unclear and cortactin research rather focuses on
      its homologue hematopoietic lineage cell-specific protein-1 (HS1). A fascin
      nanobody (FASNb5) that inhibits actin bundling and a cortactin nanobody (CORNb2)
      specifically targeting its Src-homology 3 (SH3) domain were used as unique tools
      to study the function of these regulators in podosome dynamics in both THP-1
      macrophages and dendritic cells (DC). Upon intracellular FASNb5 expression, the
      few podosomes present were aberrantly stable, long-living and large, suggesting a
      role for fascin actin bundling in podosome turnover and disassembly. Fascin
      modulates this by balancing the equilibrium between branched and bundled actin
      networks. In the presence of CORNb2, the few podosomes formed show disrupted
      structures but their dynamics were unaffected. This suggests a role of the
      cortactin SH3 domain in podosome assembly. Remarkably, both nanobody-induced
      podosome-losses were compensated for by focal adhesion structures. Furthermore,
      matrix degradation capacities were altered and migratory phenotypes were lost. In
      conclusion, the cortactin SH3 domain contributes to podosome assembly while
      fascin actin bundling is a master regulator of podosome disassembly in THP-1
      macrophages and DC. 

PMID- 25601715
TI  - A survey for endodontists in today's economy: exploring the current state of
      endodontics as a profession and the relationship between endodontists and their
      referral base.
AB  - INTRODUCTION: The purpose of this study was to assess the perceptions, referral
      trends, and practice patterns of practicing endodontists in the United States and
      any effect the recent economy may have had on these. METHODS: A 24-question
      survey was formulated and sent via www.surveymonkey.com to 3255 active members of
      the American Association of Endodontists. Overall, 875 participants completed the
      survey, a response rate of 26.9%. RESULTS: The average number of treatment cases
      per day was 5.7. Average work hours per week were 34.3 for men and 30.7 for women
      (P < .05). Among all treatment cases, 46% were nonsurgical retreatment, and 7.2%
      were apical surgical procedures. Procedural misadventure accounted for 10.8% of
      all treatment cases, with the most common referral reason being unable to locate
      canals (75.0%) followed by separated instruments (15.3%). Of all respondents,
      49.9% performed regenerative endodontic procedures, and 7.7% placed implants.
      Among endodontists who practice in urban areas, 69.7% believed there were too
      many endodontists, and 50% have delayed their retirement plans because of recent
      economic impact, compared with their suburban and rural counterparts at 66.1% and
      38%, 25.9% and 33.1%, respectively (P < .05). Fifty-nine percent of respondents
      were optimistic about the future of endodontics as a specialty, but those who
      have practiced more than 20 years were more pessimistic than those with less
      experience (P < .05). CONCLUSIONS: Recent economic impacts appear to have had an
      effect on the perceptions of active endodontists regarding practice success, the
      future of the specialty, and their retirement plans. Those who have been in
      practice longest (>20 years), practice in urban settings, and practice in a solo
      environment are most significantly affected.

PMID- 25601716
TI  - Pulpal response after acute dental injury in the permanent dentition: clinical
      implications-a review.
AB  - INTRODUCTION: Pulpal reactions after acute dental injury have been puzzling for
      many clinicians. The management of dental trauma and an understanding of clinical
      and treatment factors in outcomes arose from multivariate statistical analyses of
      archive material from Copenhagen. METHODS: The aim of this article was to review
      the works of this period with respect to pulpal reaction after acute mechanical
      trauma. These traumas include luxation, avulsion, root fracture, and crown
      fracture. A PubMed search identified other literature where multivariate analysis
      was used, and these results were compared with earlier pioneering studies.
      RESULTS AND CONCLUSIONS: This article will describe pulpal responses after the
      said acute injuries and outline the competition that takes place between ingrowth
      of a new neurovascular system into the traumatized tissue versus bacterial
      invasion. If there is an intact neurovascular supply to the pulp, then the same
      immunologic defenses that are found in the rest of the body can function and
      defend against infection. If this is disturbed in any way, alterations in the
      pulp (eg, pulp canal obliteration, resorption processes) or pulp death (pulp
      necrosis) will occur. Intermediary stations in pulpal response (ie, transient
      apical breakdown) mimicked the cardinal signs of pulp necrosis, which could be
      reversible and lead to pulpal healing. These processes will also be addressed
      with respect to a more conservative treatment approach. In young patients, it is
      of the utmost importance that pulp vitality be maintained to ensure continued
      root growth and development and an intact dentition.

PMID- 25601714
TI  - Hsf4 counteracts Hsf1 transcription activities and increases lens epithelial cell
      survival in vitro.
AB  - The interplay between Hsf4 and Hsf1 plays an important role in the regulation of
      lens homeostasis. However, the mechanism of the intermolecular association
      involved is still unclear. In this paper, we find that reconstitution of Hsf4b
      into Hsf4-/- lens epithelial (mLEC/Hsf4-/-) cells can simultaneously downregulate
      Hsp70 expression and upregulate the expression of small heat shock proteins Hsp25
      and alphaB-crystallin at both RNA and protein levels. ChIP assay results indicate
      Hsf4b, which binds to the promoters of Hsp90alpha, Hsp70.3, Hsp25 and alphaB
      crystallin but not Hsp70.1, can inhibit Hsf1 binding to Hsp70.3 promoter and the
      heat shock mediated Hsp70 promoter activity by reducing Hsf1 protein expression.
      Hsf4b N-terminal hydrophobic region can interact with Hsf1 N-terminal hydrophobic
      region. Their interaction impairs Hsf1's intramolecular interaction between the N
      and C-terminal hydrophobic regions, leading to Hsf1's cytosolic retention and
      protein degradation. Both lysosome inhibitors (chloroquine, pepstatin A plus
      E64d) and proteasome inhibitor MG132 can inhibit Hsf4-mediated Hsf1 protein
      degradation, but MG132 can induce Hsf1 activation as well. Upregulation of Hsf4b
      can significantly inhibit cisplatin and staurosporine induced lens epithelial
      cell apoptosis through direct upregulation of Hsp25 and alphaB-crystallin
      expression. Taken together, our results imply that upregulation of Hsf4b
      modulates the expression pattern of heat shock proteins in lens tissue by either
      directly binding to their promoters or promoting Hsf1 protein degradation.
      Moreover, upregulation of Hsf4b protects lens cell survival by upregulating anti
      apoptotic pathways. These studies reveal a novel regulatory mechanism between
      Hsf1 and Hsf4b in modulating lens epithelial cell homeostasis.

PMID- 25601712
TI  - Acute ethanol induces apoptosis by stimulating TRPC6 via elevation of superoxide
      in oxygenated podocytes.
AB  - Our recent studies indicate that hydrogen peroxide (H2O2) only at high
      concentrations can cause oxidative stress in renal epithelial cells and induce
      apoptosis of podocytes. Consistently, the present study shows that H2O2, even at
      1 mM, failed to induce intracellular oxidative stress and apoptosis of the
      podocytes due to efficient activity of catalase, an enzyme which degrades H2O2 to
      produce water and oxygen (O2). However, H2O2 acted as a source of O2 to allow
      acute ethanol to induce superoxide production and cause apoptosis of the
      podocytes. In contrast, acute ethanol alone did not elevate intracellular
      superoxide, even though it stimulates expression and translocation of p47phox to
      the plasma membrane. Inhibition of catalase abolished not only O2 production from
      H2O2 degradation, but also NOX2-dependent superoxide production in the podocytes
      challenged by both H2O2 and acute ethanol. In parallel, acute ethanol in the
      presence of H2O2, but neither ethanol nor H2O2 alone, stimulated transient
      receptor potential canonical 6 (TRPC6) channels and caused TRPC6-dependent
      elevation of intracellular Ca2+. These data suggest that exogenous H2O2 does not
      induce oxidative stress due to rapid degradation to produce O2 in the podocytes,
      but the oxygenated podocytes become sensitive to acute ethanol challenge and
      undergo apoptosis via a TRPC6-dependent elevation of intracellular Ca2+. Since
      cultured podocytes are considered in hypoxic conditions, H2O2 may be used as a
      source of O2 to establish an ischemia-reperfusion model in some type of cultured
      cells in which H2O2 does not directly induce intracellular oxidative stress.

PMID- 25601717
TI  - Evaluation of a new protocol for removing metal retainers from multirooted teeth.
AB  - INTRODUCTION: The aim of this study was to evaluate in vitro a new protocol for
      removing intraradicular retainers from multirooted teeth applying ultrasonic
      vibration. METHODS: Forty mandibular molars were endodontically treated to
      receive cast intraradicular retainers, which were distributed into the following
      4 groups: group 1: control without a slot and without ultrasound, group 2:
      control with a slot and without ultrasound, group 3: ultrasonic vibration in the
      core without a slot, and group 4: ultrasonic vibration in the core with a slot.
      After the intraradicular retainers were cemented with zinc phosphate, ultrasonic
      vibration was applied for 1 minute. The test specimens were then submitted to the
      traction test in the universal testing machine at a speed of 1 mm/min. The
      maximum traction force required to remove the intraradicular retainer was
      recorded in newtons, and the data were statistically analyzed using analysis of
      variance and the Tukey-Kramer test (P < .05). RESULTS: The results showed
      statistically significant differences among the groups tested (group 1 = 234.34
      N, group 2 = 201.67 N, group 3 = 139.57 N, and group 4 = 83.23 N). The lowest
      mean value of traction force recorded was when ultrasonic vibration was applied
      on the core with a slot. CONCLUSIONS: Creating a slot in the core and the
      ultrasound application on all surfaces and inside the slot reduced the force
      required for removing intraradicular metal retainers from multirooted teeth
      cemented with zinc phosphate.

PMID- 25601718
TI  - Designing a deep brain stimulator to suppress pathological neuronal synchrony.
AB  - Some of neuropathologies are believed to be related to abnormal synchronization
      of neurons. In the line of therapy, designing effective deep brain stimulators to
      suppress the pathological synchrony among neuronal ensembles is a challenge of
      high clinical relevance. The stimulation should be able to disrupt the synchrony
      in the presence of latencies due to imperfect knowledge about parameters of a
      neuronal ensemble and stimulation impacts on the ensemble. We propose an adaptive
      desynchronizing deep brain stimulator capable of dealing with these
      uncertainties. We analyze the collective behavior of the stimulated neuronal
      ensemble and show that, using the designed stimulator, the resulting asynchronous
      state is stable. Simulation results reveal the efficiency of the proposed
      technique. 

PMID- 25601719
TI  - Evaluation of an otoscopy simulator to teach otoscopy and normative anatomy to
      first year medical students.
AB  - OBJECTIVE/HYPOTHESIS: Our study evaluates the effectiveness of the OtoSim as an
      educational tool for teaching otoscopy and normal middle ear anatomy to first
      year medical students. STUDY DESIGN: Cross-sectional survey design. METHODS: A
      large group otoscopy simulator teaching session was held in January 2014 for 29
      first-year medical students at the University of Toronto. Following the training
      session, survey questions were administered to assess the student experience.
      RESULTS: A total of 29 students completed the survey. All respondents rated the
      overall quality of the event as very good or excellent. Ninety-three percent of
      respondents indicated that the simulator increased their confidence in otoscopy.
      Students also commented that they were able to learn normal middle ear anatomy
      without causing discomfort to patients. CONCLUSIONS: The use of otoscopy
      simulation is a novel addition to traditional learning methods for undergraduate
      medical students. Students can effectively learn normal external and middle ear
      anatomy and improve their confidence in performing otoscopy examination. LEVEL OF
      EVIDENCE: NA.

PMID- 25601720
TI  - Clearly written, easily comprehended? The readability of websites providing
      information on epilepsy.
AB  - There is a general need for high-quality, easily accessible, and comprehensive
      health-care information on epilepsy to better inform the general population about
      this highly stigmatized neurological disorder. The aim of this study was to
      evaluate the health literacy level of eight popular English-written websites that
      provide information on epilepsy in quantitative terms of readability. Educational
      epilepsy material on these websites, including 41 Wikipedia articles, were
      analyzed for their overall level of readability and the corresponding academic
      grade level needed to comprehend the published texts on the first reading. The
      Flesch Reading Ease (FRE) was used to assess ease of comprehension while the
      Gunning Fog Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Automated
      Readability Index, and Simple Measure of Gobbledygook scales estimated the
      corresponding academic grade level needed for comprehension. The average
      readability of websites yielded results indicative of a difficult-to-fairly
      difficult readability level (FRE results: 44.0+/-8.2), with text readability
      corresponding to an 11th academic grade level (11.3+/-1.9). The average FRE score
      of the Wikipedia articles was indicative of a difficult readability level (25.6+/
      9.5), with the other readability scales yielding results corresponding to a 14th
      grade level (14.3+/-1.7). Popular websites providing information on epilepsy,
      including Wikipedia, often demonstrate a low level of readability. This can be
      ameliorated by increasing access to clear and concise online information on
      epilepsy and health in general. Short "basic" summaries targeted to patients and
      nonmedical users should be added to articles published in specialist websites and
      Wikipedia to ease readability. 

PMID- 25601721
TI  - [Allergic contact eczema to a long-used cosmetic: Methylisothiazolinon, a type IV
      allergen].
AB  - Methylisothiazolinone was permitted in 2004 as preservative in rinse-off and
      leave-on products by the European cosmetics directive. This led to a dramatic
      increase in contact eczemas induced by MI in the past few years. Here, we report
      a patient who developed a spreading contact eczema of the face, neck and proximal
      arms mimicking a photodermatosis. The reaction was caused by use of a facial
      ointment that only recently started to contain MI. Type IV-sensitization to MI
      was verified by patch testing.

PMID- 25601722
TI  - Analysis of Coupled Reaction-Diffusion Equations for RNA Interactions.
AB  - We consider a system of coupled reaction-diffusion equations that models the
      interaction between multiple types of chemical species, particularly the
      interaction between one messenger RNA and different types of non-coding microRNAs
      in biological cells. We construct various modeling systems with different levels
      of complexity for the reaction, nonlinear diffusion, and coupled reaction and
      diffusion of the RNA interactions, respectively, with the most complex one being
      the full coupled reaction-diffusion equations. The simplest system consists of
      ordinary differential equations (ODE) modeling the chemical reaction. We present
      a derivation of this system using the chemical master equation and the mean-field
      approximation, and prove the existence, uniqueness, and linear stability of
      equilibrium solution of the ODE system. Next, we consider a single, nonlinear
      diffusion equation for one species that results from the slow diffusion of the
      others. Using variational techniques, we prove the existence and uniqueness of
      solution to a boundary-value problem of this nonlinear diffusion equation.
      Finally, we consider the full system of reaction-diffusion equations, both steady
      state and time-dependent. We use the monotone method to construct iteratively
      upper and lower solutions and show that their respective limits are solutions to
      the reaction-diffusion system. For the time-dependent system of reaction
      diffusion equations, we obtain the existence and uniqueness of global solutions.
      We also obtain some asymptotic properties of such solutions.

PMID- 25601723
TI  - Mild and selective activation and substitution of strong aliphatic C-F bonds.
AB  - A procedure for chemoselectively manipulating the strong aliphatic C-F bond with
      direct transformation into a C-N bond under mild conditions is reported. The
      activation and subsequent substitution of primary alkyl fluorides is mediated by
      La[N(SiMe3)2]3, and results in high to excellent yields of tertiary amines. The
      methodology displays high selectivity towards the C(sp(3))-F bond, and a variety
      of secondary amines are applicable as nucleophiles. Mechanistic investigations
      reveal a reaction that is first order with respect to [La[N(SiMe3)2]3],
      [R(1)R(2)NH], and [alkyl fluoride], and a 6-membered cyclic transition state is
      proposed. In addition, (1)H NMR spectroscopy shows that La[N(SiMe3)2]3 is the
      active species involved in the substitution and that protonolysis of the amine,
      yielding La[NR(1)R(2)]3, lowers the reactivity.

PMID- 25601724
TI  - Secular changes in prediabetes indicators among older-adult Americans, 1999-2010.
AB  - BACKGROUND: Sex-specific prediabetes estimates are not available for older-adult
      Americans. PURPOSE: To estimate prediabetes prevalence, using nationally
      representative data, in civilian, non-institutionalized, older U.S. adults.
      METHODS: Data from 7,995 participants aged >=50 years from the 1999-2010 National
      Health and Nutrition Examination Surveys were analyzed in 2013. Prediabetes was
      defined as hemoglobin A1c=5.7%-6.4% (39-47 mmol/mol [HbA1c5.7]), fasting plasma
      glucose of 100-125 mg/dL (impaired fasting glucose [IFG]), or both. Crude and age
      adjusted prevalences for prediabetes, HbA1c5.7, and IFG by sex and three age
      groups were calculated, with additional adjustment for sex, age, race/ethnicity,
      poverty status, education, living alone, and BMI. RESULTS: From 1999 to 2005 and
      2006 to 2010, prediabetes increased for adults aged 50-64 years (38.5% [95%
      CI=35.3, 41.8] to 45.9% [42.3, 49.5], p=0.003) and 65-74 years (41.3% [37.2,
      45.5] to 47.9% [44.5, 51.3]; p=0.016), but not significantly for adults aged >=75
      years (45.1% [95% CI=41.1, 49.1] to 48.9% [95% CI=45.2, 52.6]; p>0.05).
      Prediabetes increased significantly for women in the two youngest age groups, and
      HbA1c5.7 for both sexes (except men aged >=75 years), but IFG remained stable for
      both sexes. Men had higher prevalences than women for prediabetes and IFG among
      adults aged 50-64 years, and for IFG among adults aged >=75 years. Across
      demographic subgroups, adjusted prevalence gains for both sexes were similar and
      most pronounced for HbA1c5.7, virtually absent for IFG, but greater for women
      than men for prediabetes. CONCLUSIONS: Given the large, growing prediabetes
      prevalence and its anticipated burden, older adults, especially women, are likely
      intervention targets.

PMID- 25601727
TI  - Temporal-spatial variations of the physicochemical characteristics of air
      pollution Particulate Matter (PM2.5-0.3) and toxicological effects in human
      bronchial epithelial cells (BEAS-2B).
AB  - While the evidence for the health adverse effects of air pollution Particulate
      Matter (PM) has been growing, there is still uncertainty as to which constituents
      within PM are most harmful. Hence, to contribute to fulfill this gap of
      knowledge, some physicochemical characteristics and toxicological endpoints (i.e.
      cytotoxicity, oxidative damage, cytokine secretion) of PM2.5-0.3 samples produced
      during two different seasons (i.e. spring/summer or autumn/winter) in three
      different surroundings (i.e. rural, urban, or industrial) were studied, thereby
      expecting to differentiate their respective adverse effects in human bronchial
      epithelial cells (BEAS-2B). Physicochemical characteristics were closely related
      to respective origins and seasons of the six PM2.5-0.3 samples, highlighting the
      respective contributions of industrial and heavy motor vehicle traffic sources.
      Space- and season-dependent differences in cytotoxicity of the six PM2.5-0.3
      samples could only be supported by considering both the physicochemical
      properties and the variance in air PM concentrations. Whatever spaces and
      seasons, dose- and even time-dependent increases in oxidative damage and cytokine
      secretion were reported in PM2.5-0.3-exposed BEAS-2B cells. However, the
      relationship between the chemical composition of each of the six PM2.5-0.3
      samples and their oxidative or inflammatory potentials seemed to be very complex.
      These results supported the role of inorganic, ionic and organic components as
      exogenous source of Reactive Oxygen Species and, thereafter, cytokine secretion.
      Nevertheless, one of the most striking observation was that some inorganic, ionic
      and organic chemical components were preferentially associated with early
      oxidative events whereas others in the later oxidative damage and/or cytokine
      secretion. Taken together, these results indicated that PM mass concentration
      alone might not be able to explain the health outcomes, because PM is chemically
      nonspecific, and supported growing evidence that PM-size, composition and
      emission source, together with sampling season, interact in a complex manner to
      produce PM2.5-0.3-induced human adverse health effects. 

PMID- 25601729
TI  - The associations between ambient air pollution and adult respiratory mortality in
      32 major Chinese cities, 2006-2010.
AB  - BACKGROUND: China has experienced increasingly severe levels of air pollution in
      the past decades, yet studies on the health effects of air pollution in China at
      a national study level, remain limited. This study assess the sub-chronic effect
      of ambient air pollution on respiratory mortality in the 32 largest Chinese
      cities. METHODS: We employ two-way fixed effects panel data analysis and monthly
      air pollution and mortality panel data. We estimate associations between monthly
      respiratory mortality and air pollution; pollution is defined as particulate
      matter with aerodynamic diameter <10MUm. We adjust for city characteristics,
      seasonality (monthly effects), and weather conditions (precipitation and
      temperature). We examine the associations between monthly injury mortality and
      air pollution to check for robustness. RESULTS: The results show positive and
      statistically significant associations of air pollution with respiratory
      mortality. During the study period (2006-2010) a 10MUg/m(3) increase in monthly
      PM10 concentration is associated with a 1.05% (95% CI, 0.08-2.04%) increase in
      adult respiratory mortality rate. The air pollution effect is the most salient in
      northern cities (with central heating system) during the cold season (October
      April); a 10MUg/m(3) increase in monthly PM10 concentrations is associated with a
      1.62% (95% CI, 0.22-3.46%) increase in the elderly respiratory mortality rate.
      There is no statistically significant association between the young adult
      respiratory mortality and air pollution. CONCLUSIONS: The elderly respiratory
      mortality rate in China is positively and statistically significantly associated
      with air pollution. The effect is largest in northern cities during cold months
      when coal is burned for heating.

PMID- 25601730
TI  - Penile density and globally used chemicals in Canadian and Greenland polar bears.
AB  - Industrially produced chemicals have been a major environmental concern across
      our entire Globe since the onset of rapid industrial development around the early
      1900. Many of the substances being used are known to be endocrine disrupting
      chemicals (EDCs) and are also known to be long-range dispersed and to biomagnify
      to very high concentrations in the tissues of Arctic apex predators such as polar
      bears (Ursus maritimus). A major concern relating to EDCs is their effects on
      vital organ-tissues such as bone and it is possible that EDCs represent a more
      serious challenge to the species' survival than the more conventionally proposed
      prey reductions linked to climate change. We therefore analyzed penile bone
      mineral density (BMD) as a key phenotype for reproductive success in 279 polar
      bear samples born 1990-2000 representing eight polar bear subpopulations. Since
      EDC concentrations were not available from the same specimens, we compared BMD
      with published literature information on EDC concentrations. Latitudinal and
      longitudinal BMD and EDC gradients were clearly observed, with Western Hudson
      bears having the highest BMD and lowest EDCs, and North East Greenland polar
      bears carrying the lowest BMD and highest EDCs. A BMD vs. polychlorinated
      biphenyls (PCB) regression analysis showed that BMD decreased as a function of
      the eight subpopulations' PCB concentrations and this relationship was close to
      being significant (p=0.10, R(2)=0.39). Risk quotient (RQ) estimation demonstrated
      that PCBs could be in a range that may lead to disruption of normal reproduction
      and development. It is therefore likely that EDCs directly affect development and
      bone density in polar bears. Canadian bears had in general the best health and
      the North East Greenland subpopulation being at the highest risk of having
      negative health effects. While reductions in BMD is in general unhealthy,
      reductions in penile BMD could lead to increased risk of species extinction
      because of mating and subsequent fertilization failure as a result of weak penile
      bones and risk of fractures. Based on this, future studies should assess how
      polar bear subpopulations respond upon EDC exposure since information and
      understanding about their circumpolar reproductive health is vital for future
      conservation. 

PMID- 25601728
TI  - Associations between prenatal traffic-related air pollution exposure and birth
      weight: Modification by sex and maternal pre-pregnancy body mass index.
AB  - BACKGROUND: Prenatal traffic-related air pollution exposure is linked to adverse
      birth outcomes. However, modifying effects of maternal body mass index (BMI) and
      infant sex remain virtually unexplored. OBJECTIVES: We examined whether
      associations between prenatal air pollution and birth weight differed by sex and
      maternal BMI in 670 urban ethnically mixed mother-child pairs. METHODS: Black
      carbon (BC) levels were estimated using a validated spatio-temporal land-use
      regression (LUR) model; fine particulate matter (PM2.5) was estimated using a
      hybrid LUR model incorporating satellite-derived Aerosol Optical Depth measures.
      Using stratified multivariable-adjusted regression analyses, we examined whether
      associations between prenatal air pollution and calculated birth weight for
      gestational age (BWGA) z-scores varied by sex and maternal pre-pregnancy BMI.
      RESULTS: Median birth weight was 3.3+/-0.6kg; 33% of mothers were obese (BMI
      >=30kg/m(3)). In stratified analyses, the association between higher PM2.5 and
      lower birth weight was significant in males of obese mothers (-0.42 unit of BWGA
      z-score change per IQR increase in PM2.5, 95%CI: -0.79 to -0.06) (
      PM2.5*sex*obesity Pinteraction=0.02). Results were similar for BC models
      (Pinteraction=0.002). CONCLUSIONS: Associations of prenatal exposure to traffic
      related air pollution and reduced birth weight were most evident in males born to
      obese mothers.

PMID- 25601726
TI  - Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the
      Regulation of Brain Immune Responses.
AB  - The concept of the central nervous system (CNS) as an immune-privileged site,
      essentially due to the presence of the blood brain barrier, appears to be overly
      simplistic. Indeed, within healthy CNS immune activities are permitted and are
      required for neuronal function and host defense, not only due to the presence of
      the resident innate immune cells of the brain, but also by virtue of a complex
      cross-talk of the CNS with peripheral immune cells. Nonetheless, long-standing
      and persisting neuroinflammatory responses are most often detrimental and
      characterize several neuroinflammatory diseases, including multiple sclerosis,
      Alzheimer's disease and amyotrophic lateral sclerosis. A growing body of evidence
      suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic
      cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory
      properties, both in peripheral tissues and in the CNS, through the activation of
      cannabinoid receptors. In this review, the immunomodulatory effects of
      cannabinoid signaling on the most relevant brain immune cells will be discussed.
      In addition, the impact of cannabinoid regulation on the overall integration of
      the manifold brain immune responses will also be highlighted, along with the
      implication of these compounds as potential agents for the management of
      neuroinflammatory disorders. 

PMID- 25601731
TI  - Associations between urinary organophosphate pesticide metabolite levels and
      reproductive parameters in men from an infertility clinic.
AB  - Organophosphate (OP) pesticides are compounds used for pest control at home or in
      agriculture activities. Almost all OP pesticides are metabolized to at least one
      of six possible dialkylphosphates (DAPs). Despite wide use, their potential
      effects on human reproductive health have not yet been fully characterized. The
      aim of this study was to evaluate the associations between urinary concentrations
      of six DAP metabolites and reproductive parameters in men. All men were attended
      an infertility clinic and provided urine, serum and semen samples on the same
      day. Six DAP metabolites were measured in urine (dimethylphosphate [DMP],
      dimethylthiophosphate [DMTP], dimethyldithiophosphate [DMDTP], diethylphosphate
      [DEP], diethylthiophosphate [DETP], and diethyldithiophosphate [DEDTP]). Sperm
      quality was assessed by measuring volume, concentration, total sperm count (TSC),
      motility and morphology, and serum samples were analyzed for reproductive
      hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      testosterone, prolactin and estradiol. Pearson correlations were used for
      unadjusted analyses, and multiple linear regression analysis was performed
      controlling for appropriate covariates. All men presented detectable
      concentrations of at least one urinary OP metabolite. After adjustment by
      important covariates, there was a significant positive association between DEDTP
      concentrations and LH [(beta)=11.4; 95% CI 0.81-22.1] as well as FSH levels
      [(beta)=3.2; 95% CI 0.08-6.2]. Sperm concentration and TSC were both
      significantly inversely associated with DMP, DMDP, DMDTP and ?DAP in multivariate
      analysis. Besides, there was a significant inverse association between percentage
      of motile sperm and DMTP, DMDTP and DEP metabolite concentrations. Our results
      suggest that exposure to OP pesticides may be associated with decreased sperm
      counts and motility and altered reproductive hormone levels in male partners of
      couples seeking for infertility treatment. However, further studies are warranted
      to confirm and extent these findings. 

PMID- 25601732
TI  - Nitrate in drinking water and bladder cancer risk in Spain.
AB  - BACKGROUND: Nitrate is a widespread contaminant in drinking water and ingested
      nitrate under conditions resulting in endogenous nitrosation is suspected to be
      carcinogenic. However, the suggested association between nitrate in drinking
      water and bladder cancer remains inconsistent. We evaluated the long-term
      exposure to drinking water nitrate as a risk factor for bladder cancer,
      considering endogenous nitrosation modifiers and other covariables. METHODS: We
      conducted a hospital-based case-control study of bladder cancer in Spain (1998
      2001). Residential histories and water consumption information were ascertained
      through personal interviews. Historical nitrate levels (1940-2000) were estimated
      in study municipalities based on monitoring records and water source. Residential
      histories of study subjects were linked with nitrate estimates by year and
      municipality to calculate individual exposure from age 18 to recruitment. We
      calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer
      among 531 cases and 556 controls with reliable interviews and nitrate exposure
      information covering at least 70% of years from age 18 to interview. RESULTS:
      Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions.
      Adjusted OR (95%CI) for average residential levels relative to <= 5 mg/L were 1.2
      (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with
      longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9
      2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer
      diagnosis did not modify these results. A non-significant negative association
      was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs.
      <= 4 mg/day. Adjustment for several covariables showed similar results to crude
      analyses. CONCLUSION: Bladder cancer risk was inconsistently associated with
      chronic exposure to drinking water nitrate at levels below the current regulatory
      limit. Elevated risk is suggested only among subjects with longest exposure
      duration to the highest levels. No evidence of interaction with endogenous
      nitrosation modifiers was observed.

PMID- 25601733
TI  - A land use regression model for estimating the NO2 concentration in Shanghai,
      China.
AB  - Limited by data accessibility, few exposure assessment studies of air pollutants
      have been conducted in China. There is an urgent need to develop models for
      assessing the intra-urban concentration of key air pollutants in Chinese cities.
      In this study, a land use regression (LUR) model was established to estimate NO2
      during 2008-2011 in Shanghai. Four predictor variables were left in the final LUR
      model: the length of major road within the 2-km buffer around monitoring sites,
      the number of industrial sources (excluding power plants) within a 10-km buffer,
      the agricultural land area within a 5-km buffer, and the population counts. The
      model R(2) and the leave-one-out-cross-validation (LOOCV) R(2) of the NO2 LUR
      models were 0.82 and 0.75, respectively. The prediction surface of the NO2
      concentration based on the LUR model was of high spatial resolution. The 1-year
      predicted concentration based on the ratio and the difference methods fitted well
      with the measured NO2 concentration. The LUR model of NO2 outperformed the
      kriging and inverse distance weighed (IDW) interpolation methods in Shanghai. Our
      findings suggest that the LUR model may provide a cost-effective method of air
      pollution exposure assessment in a developing country. 

PMID- 25601735
TI  - Estimating risk of emergency room visits for asthma from personal versus fixed
      site measurements of NO2.
AB  - BACKGROUND: We examined the impact of data source and exposure measurement error
      for ambient NO2 on risk estimates derived from a case-crossover study of
      emergency room visits for asthma in Windsor, Canada between 2002 and 2009.
      METHODS: Paired personal and fixed-site NO2 data were available from an
      independent population (47 children and 48 adults) in Windsor between 2005 and
      2006. We used linear regression to estimate the relationship and measurement
      error variance induced between fixed site and personal measurements of NO2, and
      through a series of simulations, evaluated the potential for a Bayesian model to
      adjust for this change in scale and measurement error. Finally, we re-analyzed
      data from the previous case-crossover study adjusting for the estimated change in
      slope and measurement error. RESULTS: Correlations between paired NO2
      measurements were weak (R(2)<=0.08) and slopes were far from unity
      (0.0029<=beta<=0.30). Adjusting the previous case-crossover analysis suggested a
      much stronger association between personal NO2 (per 1ppb) (Odds Ratio (OR)=1.276,
      95% Credible Interval (CrI): 1.034, 1.569) and emergency room visits for asthma
      among children relative to the fixed-site estimate (OR=1.024, 95% CrI 1.004
      1.045). CONCLUSIONS: Our findings suggest that risk estimates based on fixed-site
      NO2 concentrations may differ substantially from estimates based on personal
      exposures if the change in scale and/or measurement error is large. In practice,
      one must always keep the scale being used in mind when interpreting risk
      estimates and not assume that coefficients for ambient concentrations reflect
      risks at the personal level.

PMID- 25601734
TI  - Preconception and early pregnancy air pollution exposures and risk of gestational
      diabetes mellitus.
AB  - BACKGROUND: Air pollution has been linked to gestational diabetes mellitus (GDM)
      but no studies have evaluated impact of preconception and early pregnancy air
      pollution exposures on GDM risk. METHODS: Electronic medical records provided
      data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM
      (n=208,618). Average maternal exposures to particulate matter (PM) <= 2.5MUm
      (PM2.5) and PM2.5 constituents, PM <= 10MUm (PM10), nitrogen oxides (NOx), carbon
      monoxide, sulfur dioxide (SO2) and ozone (O3) were estimated for the 3-month
      preconception window, first trimester, and gestational weeks 1-24 based on
      modified Community Multiscale Air Quality models for delivery hospital referral
      regions. Binary regression models with robust standard errors estimated relative
      risks (RR) for GDM per interquartile range (IQR) increase in pollutant
      concentrations adjusted for study site, maternal age and race/ethnicity. RESULTS:
      Preconception maternal exposure to NOX (RR=1.09, 95% CI: 1.04, 1.13) and SO2
      (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and
      risk estimates remained elevated for first trimester exposure. Preconception O3
      was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks
      increased later in pregnancy. CONCLUSION: Maternal exposures to NOx and SO2
      preconception and during the first few weeks of pregnancy were associated with
      increased GDM risk. O3 appeared to increase GDM risk in association with mid
      pregnancy exposure but not in earlier time windows. These common exposures merit
      further investigation.

PMID- 25601736
TI  - Neurobehavioral effects of arsenic exposure among secondary school children in
      the Kandal Province, Cambodia.
AB  - The research was carried out at 3 study sites with varying groundwater arsenic
      (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen
      as a highly contaminated site (300-500MUg/L), Svay Romiet Commune was chosen as a
      moderately contaminated site (50-300MUg/L) and Anlong Romiet Commune was chosen
      as a control site. Neurobehavioral tests on the 3 exposure groups were conducted
      using a modified WHO neurobehavioral core test battery. Seven neurobehavioral
      tests including digit symbol, digit span, Santa Ana manual dexterity, Benton
      visual retention, pursuit aiming, trail making and simple reaction time were
      applied. Children's hair samples were also collected to investigate the influence
      of hair As levels on the neurobehavioral test scores. The results from the
      inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples
      showed that hair As levels at the 3 study sites were significantly different
      (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a
      median hair As level of 0.93MUg/g, while the moderately contaminated site (n=151)
      had a median hair As level of 0.22MUg/g, and the control site (n=214) had a
      median hair As level of 0.08MUg/g. There were significant differences among the 3
      study sites for all the neurobehavioral tests scores, except for digit span
      (backward) test. Multiple linear regression clearly shows a positive significant
      influence of hair As levels on all the neurobehavioral test scores, except for
      digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn)
      and cadmium (Cd). Children with high hair As levels experienced 1.57-4.67 times
      greater risk of having lower neurobehavioral test scores compared to those with
      low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status.
      In conclusion, arsenic-exposed school children from the Kandal Province of
      Cambodia with a median hair As level of 0.93ug/g among those from the highly
      contaminated study site, showed clear evidence of neurobehavioral effects. 

PMID- 25601737
TI  - Women exposure during pregnancy to haloacetaldehydes and haloacetonitriles in
      drinking water and risk of small-for-gestational-age neonate.
AB  - BACKGROUND: Past studies have examined the effects of maternal exposure to water
      chlorination disinfection by-products (DBPs), such as trihalomethanes (THMs) and
      haloacetic acids (HAAs) during pregnancy. However, no human-based study has yet
      evaluated the effect of emerging DBPs, such as haloacetaldehydes (HAs) and
      haloacetonitriles (HANs) on small-for-gestational-age (SGA) status in newborns.
      OBJECTIVE: This study aims to assess the association between maternal multiroute
      exposure to HAs and HANs during the third trimester of pregnancy and SGA status
      at birth, among neonates delivered by women residing in the Quebec City area
      (Province of Quebec, Canada). We also evaluated the interaction between exposure
      to these emerging unregulated by-products and regulated DBPs also found in
      drinking water (THMs and HAAs), for which a positive association with adverse
      reproductive outcomes has been suggested in previous studies. METHODS: We
      conducted a population-based case-control study in the Quebec City area. SGA
      newborns (n=330) were compared to 1100 controls, with matching based on calendar
      week of birth. HA and HAN concentrations in drinking water at participant's tap
      were estimated using spatio-temporal strategy based on bimonthly measurements
      carried out at several locations in the participant's distribution system. A
      computer-assisted telephone interview was completed to collect information on
      individual habits of water consumption and water related activities in order to
      determine individual multiroute exposure. This enabled us to estimate the dose of
      HAs and HANs absorbed daily by each participant. Associations between total HA,
      HAN concentrations in drinking water and SGA were analyzed. Associations between
      the daily-absorbed doses of these emerging DBPs and SGA were also analyzed. Odds
      ratios (ORs) comparing the 4th quartile of exposure to the reference group (the
      first three quartiles) were obtained by means of conditional logistic regression,
      and controlling for potential confounders. RESULTS: Globally, no evidence of
      increased risk of SGA was found with total HA and HAN concentrations in tap water
      when participants in the 4th quartile of exposure were compared to the first
      three quartiles (OR=1.0; 95% CI [0.7-1.5] and OR=0.8; 95% CI [0.6-1.2],
      respectively). Similarly, no association was found with the daily-absorbed doses
      of total HAs or HANs (OR=0.9; 95% CI [0.6-1.3] and OR=1.1; 95% CI [0.7-1.6],
      respectively). However, a small non statistically significant association was
      found between the dose of brominated HA and SGA (OR=1.4; 95% CI [0.9-2.1]). Also,
      in spite of the lack of interaction between other DBP classes, an unexpected
      negative interaction was observed between concentration of chloral hydrate (CH)
      (which represents the main HA species), and regulated DBPs (P=0.006). CONCLUSION:
      In this population, exposure to low levels of HAs and HANs during the third
      trimester of pregnancy through drinking water was not associated to SGA status in
      newborns. Nonetheless, more research is needed to clarify possible effect of
      brominated compounds and interaction between different DBPs.

PMID- 25601739
TI  - Exposure to visible mould or dampness at home and sleep problems in children:
      Results from the LISAplus study.
AB  - BACKGROUND: Exposure to mould or dampness at home has been associated with
      adverse respiratory effects in all age groups. This exposure has also been
      related to insomnia in adults. We aimed to investigate the association between
      exposure to visible mould or dampness at home and sleep problems in children.
      METHODS: The study population consisted of 1719 10-year-old children from the
      German population-based birth cohort LISAplus with available data on current
      mould or dampness at home and sleep problems. The presence of visible mould or
      dampness at home was assessed by questionnaire. Parent-reported sleep problems of
      their child were analysed by four binary variables: presence of any sleep
      problems, problems to fall asleep, problems sleeping through the night and a 24h
      sleep time of less than 9h. Logistic regression models adjusted for study centre,
      sex, age and level of parental education were applied to examine the association
      between visible mould or dampness at home and sleep problems. Sensitivity
      analyses included a further adjustment for bedroom sharing and subgroup analyses
      in children without current allergic diseases. RESULTS: Thirteen percent of
      parents reported visible mould or dampness at home. We observed increased risks
      for all four sleep problem variables for children exposed to visible mould or
      dampness at home. Results were significant for any sleep problems (odds ratio
      (OR)=1.77 (95%-confidence interval (CI): 1.21-2.60), problems sleeping through
      the night (OR=2.52(1.27-5.00) and a short sleep time (OR=1.68(1.09-2.61)). While
      a further adjustment for bedroom sharing and the exclusion of children with
      asthma or eczema led to similar results, only the association with a short sleep
      time was still present in children without allergic rhinoconjunctivitis.
      CONCLUSION: Our data suggests that visible mould or dampness at home might
      negatively influence sleep in children. The influence of allergic
      rhinoconjunctivitis on this association needs to be investigated in future
      studies.

PMID- 25601740
TI  - Gaseous chemical compounds in indoor and outdoor air of 602 houses throughout
      Japan in winter and summer.
AB  - A nationwide survey of indoor air quality in Japan was conducted using four types
      of diffusive samplers. Gaseous chemical compounds such as carbonyls, volatile
      organic compounds (VOC), acid gases, basic gases, and ozone were measured in
      indoor and outdoor air of 602 houses throughout Japan in winter and summer. Four
      kinds of diffusive samplers were used in this study: DSD-BPE/DNPH packed with 2,4
      dinitrophenyl hydrazine and trans-1,2-bis(2-pyridyl)ethylene coated silica for
      ozone and carbonyls; VOC-SD packed with Carboxen 564 particles for volatile
      organic compounds; DSD-TEA packed with triethanolamine impregnated silica for
      acid gases; and DSD-NH3 packed with phosphoric acid impregnated silica for basic
      gases. These samplers are small and lightweight and do not require a power
      source, hence, it was possible to obtain a large number of air samples via mail
      from throughout Japan. Almost all compounds in indoor air were present at higher
      levels in summer than in winter. In particular, formaldehyde, toluene, and
      ammonia were strongly dependent on temperature, and their levels increased with
      temperature. The nitrogen dioxide concentration in indoor air particularly
      increased only during winter and was well correlated with the formic acid
      concentration (correlation coefficient=0.959). Ozone concentrations in indoor air
      were extremely low compared with the outdoor concentrations. Ozone flowing from
      outdoor air may be decomposed quickly by chemical compounds in indoor air;
      therefore, it is suggested that the indoor/outdoor ratio of ozone represents the
      ventilation of the indoor environment. 

PMID- 25601738
TI  - Early hematological and immunological alterations in gasoline station attendants
      exposed to benzene.
AB  - INTRODUCTION: Elucidation of effective biomarkers may provide tools for the early
      detection of biological alterations caused by benzene exposure and may contribute
      to the reduction of occupational diseases. This study aimed to assess early
      alterations on hematological and immunological systems of workers exposed to
      benzene. METHODS: Sixty gasoline station attendants (GSA group) and 28 control
      subjects were evaluated. Environmental and biological monitoring of benzene
      exposure was performed in blood and urine. The potential effect biomarkers
      evaluated were delta-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86
      expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The
      influence of confounding factors and toluene co-exposure were considered.
      RESULTS: Although exposures were below ACGIH (American Conference of Governmental
      Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86
      expression in monocytes and increased IL-8 levels were found in the GSA group
      compared to the control subjects. Furthermore, according to multiple linear
      regression analysis, benzene exposure was associated to a decrease in CD80 and
      CD86 expression in monocytes. CONCLUSIONS: These findings suggest, for the first
      time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86
      expression, IL-8 levels, which could be suggested as potential markers for the
      early detection of benzene-induced alterations.

PMID- 25601741
TI  - Manganese and selenium concentrations in umbilical cord serum and attention
      deficit hyperactivity disorder in childhood.
AB  - Existing evidence on the effects of manganese and selenium during fetal life on
      neurodevelopmental disorders is inadequate. This study aims to investigate the
      hypothesized relationship between fetal exposure to manganese and selenium and
      attention deficit hyperactivity disorder (ADHD) diagnosis in childhood. Children
      born between 1978 and 2000 with ADHD (n=166) were identified at the Department of
      Child and Adolescent Psychiatry in Malmo, Sweden. Controls from the same region
      (n=166) were selected from the Medical Birth Register and were matched for year
      of birth and maternal country of birth. Manganese and selenium were measured in
      umbilical cord serum. The median cord serum concentrations of manganese were
      4.3MUg/L in the cases and 4.1MUg/L in the controls. The corresponding
      concentrations of selenium were 47 and 48MUg/L. When the exposures were analyzed
      as continuous variables no associations between cord manganese or selenium
      concentration and ADHD were observed. However, children with selenium
      concentrations above the 90th percentile had 2.5 times higher odds (95%
      confidence interval 1.3-5.1) of having ADHD compared to those with concentrations
      between the 10th and 90th percentiles. There was no significant interaction
      between manganese and selenium exposure (p=0.08). This study showed no
      association between manganese concentrations in umbilical cord serum and ADHD.
      The association between ADHD diagnoses in children with relatively high cord
      selenium was unexpected and should be interpreted with caution. 

PMID- 25601742
TI  - Inverse sampling regression for pooled data.
AB  - Because pools are tested instead of individuals in group testing, this technique
      is helpful for estimating prevalence in a population or for classifying a large
      number of individuals into two groups at a low cost. For this reason, group
      testing is a well-known means of saving costs and producing precise estimates. In
      this paper, we developed a mixed-effect group testing regression that is useful
      when the data-collecting process is performed using inverse sampling. This model
      allows including covariate information at the individual level to incorporate
      heterogeneity among individuals and identify which covariates are associated with
      positive individuals. We present an approach to fit this model using maximum
      likelihood and we performed a simulation study to evaluate the quality of the
      estimates. Based on the simulation study, we found that the proposed regression
      method for inverse sampling with group testing produces parameter estimates with
      low bias when the pre-specified number of positive pools (r) to stop the sampling
      process is at least 10 and the number of clusters in the sample is also at least
      10. We performed an application with real data and we provide an NLMIXED code
      that researchers can use to implement this method.

PMID- 25601743
TI  - Integrating intensive care unit (ICU) surveillance into an ICU clinical care
      electronic system.
AB  - The intensive care unit (ICU) is the specialty with the highest prevalence of
      healthcare-associated infection (HCAI) in European hospitals and therefore a
      priority for surveillance of HCAI. Whereas surveillance is an essential part of
      an effective infection prevention and control (IPC) programme, all too often it
      consumes too much clinician and IPC team time, limiting the time available for
      quality improvement. The case for electronic surveillance is made in the
      literature from several countries on this basis. These studies indicate that
      electronic surveillance can improve validity, reduce time spent on surveillance,
      and provide opportunities for improvement in clinical decision-making and IPC
      action arising from surveillance. The Scottish ICU HAI surveillance system was
      established as part of an integrated audit and clinical care system. Investment
      in this technology infrastructure reduced the burden of data collection and has
      resulted in a focus on driving improvement in all Scottish ICUs. The experience
      in Scotland indicates that several critical components are necessary to optimize
      ICU HCAI surveillance, including: nationally agreed definitions and methods;
      national investment in information technology infrastructure to make it easier to
      follow clinical care pathways; leadership of surveillance by intensivists;
      piloting and validation to ensure confidence in the system; and strategic
      integration of national and local programmes. These elements have helped improve
      surveillance data locally, nationally, and at a European level, allowing clinical
      attention to be focused on the data rather than on the process of data
      collection. 

PMID- 25601744
TI  - Norovirus introduction routes into nursing homes and risk factors for spread: a
      systematic review and meta-analysis of observational studies.
AB  - Norovirus causes substantial morbidity and mortality in nursing homes, with high
      attack rates in residents and staff. Immediate implementation of infection
      control measures is crucial. The aim of this review was to assess the evidence
      for sources and modes of introduction of norovirus, and factors contributing to
      spread. A systematic review of the literature was performed, including peer
      reviewed original studies on outbreaks confirmed by reverse transcriptase
      polymerase chain reaction. Data on source, index case, transmission mode, attack
      rate, outbreak duration, and risk factors were extracted. Attack rate and
      outbreak duration were compared by mode of introduction. Based on the selection
      criteria, 40 outbreak reports and 18 surveillance studies were included. There is
      little systematic information available on norovirus introduction into nursing
      homes, but, from evidence obtained from outbreak reports, it was determined that
      outbreaks often start with single index cases (57.5%), associated with higher
      attack rates among residents (P = 0.02). Foodborne introduction was described for
      7% of outbreak reports that were characterized by finding multiple index cases.
      In surveillance studies only 0.7% of outbreaks was reported to be foodborne,
      28.5% as person-to-person, and 70.8% remained unknown or not mentioned. Risk
      factor analyses suggested that transmission was associated with bedside care and
      exposure to vomit. These findings lead to the following recommendations: (i) to
      standardize outbreak reports; (ii) to improve early detection and isolation of
      sporadic cases; (iii) to improve personal hygiene of staff especially with highly
      dependent residents; and (iv) to comply with protocols to avoid exposure to
      vomit.

PMID- 25601747
TI  - As number of uninsured falls, more US people report they can afford care, survey
      finds.

PMID- 25601745
TI  - Challenges of controlling a large outbreak of OXA-48 carbapenemase-producing
      Klebsiella pneumoniae in a French university hospital.
AB  - A large outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae at
      Nantes University Hospital was investigated. The index case had no history of
      travel or hospitalization abroad and had been hospitalized in the internal
      medicine department for more than one month when the epidemic strain was isolated
      from a urine sample in June 2013. Seventy-two secondary cases were detected by
      weekly screening for gastrointestinal colonization during the two phases of the
      outbreak from June to October 2013 (33 cases) and from November 2013 to August
      2014 (39 cases). Spread of the epidemic strain was attributed to the proximity
      of, and staff movement between, the infectious diseases (32 cases) and the
      internal medicine (26 cases) departments; 14 secondary cases were also observed
      in the renal transplant department following the transfer of an exposed patient
      from the infectious diseases department. Most of the patients (90%) were
      colonized and no death was linked to the epidemic strain. More than 3000 contact
      patients were reviewed and 6000 rectal swabs were performed. Initial control
      measures failed to control the outbreak owing to the late detection of the index
      case. The late implementation of three successive cohort units, the large number
      of transfers between wards, and the frequent readmission of cases contributed to
      the incomplete success of control measures. 

PMID- 25601748
TI  - Transfer and effects of 1,2,3,5,7-pentachloronaphthalene in an experimental food
      chain.
AB  - Polychlorinated naphthalenes are environmentally relevant compounds that are
      measured in biota at concentrations in the MUg/kg lipid range. Despite their
      widespread occurrence, literature data on the accumulation and effects of these
      compounds in aquatic ecosystems are sparsely available. The goal of this study
      was to gain insights into the biomagnification and effects of 1,2,3,5,7
      pentachloronaphthalene (PeCN52) in an experimental food chain consisting of
      benthic worms and juvenile rainbow trout. Worms were contaminated with PeCN52 by
      passive dosing from polydimethylsiloxane silicone. The contaminated worms were
      then used to feed the juvenile rainbow trout at 0.12, 0.25 or 0.50 MUg/g fish wet
      weight/day, and the resulting internal whole-body concentrations of the
      individual fish were linked to biological responses. A possible involvement of
      the cellular detoxification system was explored by measuring PeCN52-induced
      expression of the phase I biotransformation enzyme gene cyp1a1 and the ABC
      transporter gene abcb1a. At the end of the 28-day study, biomagnification factors
      were similar for all dietary intake levels with values between 0.5 and 0.7 kg
      lipid(fish)/kg lipid(worm). The average uptake efficiency of 60% indicated that a
      high amount of PeCN52 was transferred from the worms to the fish. Internal
      concentrations of up to 175 mg/kg fish lipid in the highest treatment level did
      not result in effects on survival, behavior, or growth of the juvenile trout, but
      were associated with the induction of phase I metabolism which was evident from
      the significant up-regulation of cyp1a1 expression in the liver. In contrast, no
      changes were seen in abcb1a transcript levels.

PMID- 25601750
TI  - Mussel-inspired adhesive and transferable free-standing films by self-assembling
      dexamethasone encapsulated BSA nanoparticles and vancomycin immobilized oxidized
      alginate.
AB  - This study developed an adhesive and transferable free-standing (FS) film with
      dual function of osteoinductivity and antibacterial activity, which was obtained
      by sequentially assembling vancomycin immobilized oxidized sodium alginate and
      dexamethasone encapsulated chitosan coated BSA nanoparticles on a poly-dopamine
      layer. The FS films enabled the dual release of vancomycin and dexamethasone. The
      FS films had excellent osteoinductivity and antibacterial activity by cell
      culture and antibacterial assay. The FS film was detached from substrates and
      transferred to non-fouling surfaces by a wet transfer method, which demonstrated
      that the adhesive FS film is potential to modify biopolymers with non-fouling
      surfaces in mild and biocompatible conditions for biomedical applications. 

PMID- 25601751
TI  - Evaluating the applicability of a semi-continuous aerosol sampler to measure
      Asian dust particles.
AB  - A Korean prototype semi-continuous aerosol sampler was used to measure Asian dust
      particles. During two dust-storm periods, concentrations of crustal and trace
      elements were significantly enriched. Dust storms are one of the most significant
      natural sources of air pollution in East Asia. The present study aimed to
      evaluate use of a Korean semi-continuous aerosol sampler (K-SAS) in observation
      of mineral dust particles during dust storm events. Aerosol slurry samples were
      collected at 60 min intervals using the K-SAS, which was operated at a sampling
      flow rate of 16.7 L min(-1) through a PM10 cyclone inlet. The measurements were
      made during dust storm events at an urban site, Gwangju in Korea, between April
      30 and May 5, 2011. The K-SAS uses particle growth technology as a means of
      collecting atmospheric aerosol particles. Concentrations of 16 elements (Al, Fe,
      Mn, Ca, K, Cu, Zn, Pb, Cd, Cr, Ti, V, Ni, Co, As, and Se) were determined off
      line in the collected slurry samples by inductively coupled plasma-mass
      spectrometry (ICP-MS). The sampling periods were classified into two types, based
      on the source regions of the dust storms and the transport pathways of the air
      masses reaching the sampling site. The first period "A" was associated with dust
      particles with high Ca content, originating from the Gobi desert regions of
      northern China and southern Mongolia. The second period "B" was associated with
      dust particles with low Ca content, originating from northeastern Chinese sandy
      deserts. The results from the K-SAS indicated noticeable differences in
      concentrations of crustal and trace elements in the two sampling periods, as a
      result of differences in the source regions of the dust storms, the air mass
      transport pathways, and the impact of smoke from forest fires. The concentrations
      of the crustal (Al, Ca, Ti, Mn, and Fe) and anthropogenic trace elements (Vi, Ni,
      Cu, Zn, As, Se, and Pb) were enriched significantly during the two dust storm
      periods. However, the crustal elements were enriched more during dust storm
      period "A", whereas concentrations of the trace elements were higher during
      period "B". Higher concentrations of K during dust storm period "B" could be
      ascribed to smoke from forest fires, in addition to soil dust emissions. This
      result is supported by a strong correlation between the crustal elements and the
      K concentrations, higher K/Al and K/Fe ratios in period "B" than those detected
      in the soil samples from the Gobi desert regions and Chinese sandy deserts, and
      the smoke from forest fires. The results of this study indicate that the K-SAS is
      a good candidate for revealing the dynamics in the concentrations of elemental
      species in Asian dust particles, as well as in urban and industrial aerosols, and
      for developing insight into their sources. 

PMID- 25601749
TI  - Modification of nanocellulose by poly-lysine can inhibit the effect of fumonisin
      B1 on mouse liver cells.
AB  - Fumonisin B1 is an important mycotoxin, mainly produced by Fusarium
      verticillioides. It has toxic effects on liver, brain, and kidney cells. The
      first aim of this study was to synthesize nanocellulose modified with poly-lysine
      (NMPL), and the second aim was to evaluate the adsorption of fumonisin B1 by
      NMPL. As third aim, the function of mouse liver cells was investigated after
      exposure to fumonisin B1, and fumonisin B1+ NMPL. In this study, NMPL was
      prepared using cross-linker, and then incubated with fumonisin B1 at controlled
      conditions. After incubation, the adsorption and release of fumonisin B1 were
      evaluated in each condition. Next, mouse liver cells were separately exposed to
      fumonisin B1, NMPL, and (fumonisin B1+NMPL). Then, the level of aniline
      aminotransferase (ALT) and aspartate aminotransferase (AST) was evaluated. It was
      found that both adsorption and release of fumonisin B1 were not affected by
      temperature and incubation time, but affected by pH and concentration of NMPL.
      Also, this study showed NMPL could adsorb fumonisin B1 in different foodstuffs.
      Importantly, although the levels of ALT and AST were increased when the cells
      were treated with fumonisin B1 alone, they were not affected when exposed to NMPL
      or (fumonisin B1+NMPL). The authors suggest that NMPL is a good adsorbent to
      remove and inhibit fumonisin B1. 

PMID- 25601752
TI  - The "Chimney approach" for transcatheter aortic valve implantation: A strategy
      for trans axillarian bareback approach in patients with no other access options.
AB  - AIM: to describe the procedural steps and to report the short term follow up of
      our initial experience with an axillarian bareback Dacron graft based technique
      that could potentially reduce the rate of vascular and ischemic complications
      during transcatheter aortic valve implantation in patients with contraindications
      to trans-femoral approach and with patent left internal mammary arterial graft to
      left anterior descending coronary artery (LIMA-LAD) or small caliber
      axillarian/subclavian arteries. METHODS AND RESULTS: Four patients were treated
      with TAVI implantation with a trans axillarian bareback approach. Three out of
      four had a patent LIMA-LAD graft. In three patients, femoral approach was not
      considered as an option for the presence of diffuse peripheral vascular disease,
      while in one for the small caliber of iliac-femoral arteries. All procedures were
      performed under general anaesthesia. No procedural complications occurred.
      CONCLUSIONS: In this initial experience, the axillarian bareback approach
      technique allowed a safe and successful TAVI implant in a subgroup of patients
      with a high risk of procedural complications due to the presence of a patent LIMA
      LAD or vessels of small caliber. Considering the increasing number of patients
      referred for TAVI, in the next future the axillarian bareback approach could
      represent a safer alternative to direct cannulation in patients with severe
      aortic stenosis with no other access options.

PMID- 25601753
TI  - ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions
      of lowered NADPH oxidase activity.
AB  - The aim of this study was to elucidate the mechanisms involved in the inhibition
      of renal gluconeogenesis occurring under conditions of lowered activity of NADPH
      oxidase (Nox), the enzyme considered to be one of the main sources of reactive
      oxygen species in kidneys. The in vitro experiments were performed on primary
      cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox
      inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent
      superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty
      (ZDF) rats, a well established model of diabetes type 2, were treated with
      apocynin solution in drinking water. The main in vitro findings are the
      following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis,
      inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key
      enzyme of the process; (2) in the presence of the above-noted compounds the
      expression of PEPCK and the phosphorylation of transcription factor CREB and
      ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5
      ((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the
      rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL.
      The observed apocynin in vivo effects include: (1) slight attenuation of
      hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal
      PEPCK activity and content. In view of the results summarized above, it can be
      concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance
      for the inhibition of renal gluconeogenesis found under conditions of lowered
      superoxide radical production by Nox; (2) the mechanism of this phenomenon
      includes decreased PEPCK expression, resulting from diminished activity of
      transcription factor CREB; (3) apocynin-evoked inhibition of renal
      gluconeogenesis contributes to the hypoglycemic action of this compound observed
      in diabetic animals. Thus, the study has delivered some new insights into the
      recently discussed issue of the usefulness of Nox inhibition as a potential
      antidiabetic strategy. 

PMID- 25601754
TI  - Deacetylation of nuclear LC3 drives autophagy initiation under starvation.
AB  - Shuttling of macromolecules between different cellular compartments helps
      regulate the timing and extent of different cellular activities. Here, we report
      that LC3, a key initiator of autophagy that cycles between the nucleus and
      cytoplasm, becomes selectively activated in the nucleus during starvation through
      deacetylation by the nuclear deacetylase Sirt1. Deacetylation of LC3 at K49 and
      K51 by Sirt1 allows LC3 to interact with the nuclear protein DOR and return to
      the cytoplasm with DOR, where it is able to bind Atg7 and other autophagy factors
      and undergo phosphatidylethanolamine conjugation to preautophagic membranes. The
      association of deacetylated LC3 with autophagic factors shifts LC3's distribution
      from the nucleus toward the cytoplasm. Thus, an acetylation-deacetylation cycle
      ensures that LC3 effectively redistributes in an activated form from nucleus to
      cytoplasm, where it plays a central role in autophagy to enable the cell to cope
      with the lack of external nutrients.

PMID- 25601755
TI  - Cryo-EM of ribosomal 80S complexes with termination factors reveals the
      translocated cricket paralysis virus IRES.
AB  - The cricket paralysis virus (CrPV) uses an internal ribosomal entry site (IRES)
      to hijack the ribosome. In a remarkable RNA-based mechanism involving neither
      initiation factor nor initiator tRNA, the CrPV IRES jumpstarts translation in the
      elongation phase from the ribosomal A site. Here, we present cryoelectron
      microscopy (cryo-EM) maps of 80S?CrPV-STOP ? eRF1 ? eRF3 ? GMPPNP and 80S?CrPV
      STOP ? eRF1 complexes, revealing a previously unseen binding state of the IRES
      and directly rationalizing that an eEF2-dependent translocation of the IRES is
      required to allow the first A-site occupation. During this unusual translocation
      event, the IRES undergoes a pronounced conformational change to a more stretched
      conformation. At the same time, our structural analysis provides information
      about the binding modes of eRF1 ? eRF3 ? GMPPNP and eRF1 in a minimal system. It
      shows that neither eRF3 nor ABCE1 are required for the active conformation of
      eRF1 at the intersection between eukaryotic termination and recycling.

PMID- 25601758
TI  - The ratcheted and ratchetable structural states of RNA polymerase underlie
      multiple transcriptional functions.
AB  - DNA-dependent RNA polymerase (RNAP) accomplishes multiple tasks during
      transcription by assuming different structural forms. Reportedly, the "tight"
      form performs nucleotide addition to nascent RNA, while the "ratcheted" form is
      adopted for transcription inhibition. In this study, we performed Cys-pair
      crosslinking (CPX) analyses of various transcription complexes of a bacterial
      RNAP and crystallographic analyses of its backtracked and Gre-factor-bound states
      to clarify which of the two forms is adopted. The ratcheted form was revealed to
      support GreA-dependent transcript cleavage, long backtracking, hairpin-dependent
      pausing, and termination. In contrast, the tight form correlated with nucleotide
      addition, mismatch-dependent pausing, one-nucleotide backtracking, and factor
      independent transcript cleavage. RNAP in the paused/backtracked state, but not
      the nucleotide-addition state, readily transitions to the ratcheted form
      ("ratchetable"), indicating that the tight form represents two distinct
      regulatory states. The 3' end and the hairpin structure of the nascent RNA
      promote the ratchetable nature by modulating the trigger-loop conformation. 

PMID- 25601756
TI  - Interdependence of the rad50 hook and globular domain functions.
AB  - Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that
      functions as a homodimerization interface. Hook ablation phenocopies Rad50
      deficiency in all respects. Here, we focused on rad50 mutations flanking the
      Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated
      dimerization, but recombination between sister chromatids was largely unaffected.
      This may reflect that cohesin-mediated sister chromatid interactions are
      sufficient for double-strand break repair. However, Mre11 complex functions
      specified by the globular domain, including Tel1 (ATM) activation, nonhomologous
      end joining, and DNA double-strand break end resection were affected, suggesting
      that dimerization exerts a broad influence on Mre11 complex function. These
      phenotypes were suppressed by mutations within the coiled-coil and globular
      ATPase domains, suggesting a model in which conformational changes in the hook
      and globular domains are transmitted via the extended coils of Rad50. We propose
      that transmission of spatial information in this manner underlies the regulation
      of Mre11 complex functions. 

PMID- 25601760
TI  - The experience of purchaser-provider split in the implementation of family
      physician and rural health insurance in Iran: an institutional approach.
AB  - BACKGROUND: The Iranian health system, under the banner of family physician (FP)
      programme, has undergone substantial reforms to change utilization of health
      services, improve quality of care and enhance affordability. The national
      implementation of FP initiated in 2005 in parallel with rural health insurance
      (RHI) in rural areas and cities of <20 000 populations in Iran. The
      implementation of FP was the first national attempt to split the purchaser and
      provider of the primary health-care services in Iran. Using an adapted
      institutional approach, this article aims to explore the process of purchaser
      provider split (PPS) during the implementation of FP and RHI reforms, and its
      consequences for the health system in Iran. METHODS: We conducted 71 face-to-face
      interviews and three focus group discussions at national, provincial and local
      levels with policy makers, managers, researchers, health-care practitioners and
      representatives of the public. Interviews and focus groups were digitally
      recorded and transcribed verbatim. Data collection was supplemented by the review
      of relevant documents at all three levels. We analysed the data using an
      inductive-deductive framework analysis approach. RESULTS: Views towards PPS and
      its consequences on the implementation of FP were diverse. Some participants
      identified the PPS as an essential reform for undertaking the parallel
      implementation of FP and RHI. Others wondered whether the split has been
      beneficial as expected and asked for more scrutiny. CONCLUSIONS: The
      implementation of FP and RHI in Iran demonstrated the mixed effects of PPS on
      health system performance. Our research revealed that PPS did not succeed in
      changing the status quo, became a reason for fighting, misunderstanding, lack of
      co-operation and failure of the fragile partnership between the purchaser and
      provider. We advocate careful contextual preparation prior to large-scale
      application of PPS during nationwide implementation of FP in Iran as well as
      other settings.

PMID- 25601759
TI  - Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA.
AB  - Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for
      epigenetic silencing during development and cancer. Early works suggested binding
      specificity of PRC2 to certain long non-coding RNAs for recruitment to chromatin.
      More recent studies provided evidence both in favor and against this idea. Here,
      we bridge the two existing models of PRC2-RNA interaction. RepA RNA is a good
      binding partner for PRC2, while multiple non-relevant RNAs, including bacterial
      mRNAs, also bind PRC2; Kds depend to some extent on the experimental conditions.
      Human and mouse PRC2 have broadly similar RNA-binding properties in vitro.
      Examination of evidence supporting an existing model for site-specific
      recruitment of PRC2 by a well-defined RNA motif in cells reveals that results are
      PRC2 independent. We conclude that promiscuous and specific RNA-binding
      activities of PRC2 in vitro are not mutually exclusive, and that binding
      specificity in vivo remains to be demonstrated.

PMID- 25601757
TI  - WT1 recruits TET2 to regulate its target gene expression and suppress leukemia
      cell proliferation.
AB  - The TET2 DNA dioxygenase regulates cell identity and suppresses tumorigenesis by
      modulating DNA methylation and expression of a large number of genes. How TET2,
      like most other chromatin-modifying enzymes, is recruited to specific genomic
      sites is unknown. Here we report that WT1, a sequence-specific transcription
      factor, is mutated in a mutually exclusive manner with TET2, IDH1, and IDH2 in
      acute myeloid leukemia (AML). WT1 physically interacts with and recruits TET2 to
      its target genes to activate their expression. The interaction between WT1 and
      TET2 is disrupted by multiple AML-derived TET2 mutations. TET2 suppresses
      leukemia cell proliferation and colony formation in a manner dependent on WT1.
      These results provide a mechanism for targeting TET2 to a specific DNA sequence
      in the genome. Our results also provide an explanation for the mutual exclusivity
      of WT1 and TET2 mutations in AML, and suggest an IDH1/2-TET2-WT1 pathway in
      suppressing AML. 

PMID- 25601761
TI  - Cytochrome P450 2J2, a new key enzyme in cyclophosphamide bioactivation and a
      potential biomarker for hematological malignancies.
AB  - The role of cytochrome P450 2J2 (CYP2J2) in cyclophosphamide (Cy) bioactivation
      was investigated in patients, cells and microsomes. Gene expression analysis
      showed that CYP2J2 mRNA expression was significantly (P<0.01) higher in 20
      patients with hematological malignancies compared with healthy controls. CYP2J2
      expression showed significant upregulation (P<0.05) during Cy treatment before
      stem cell transplantation. Cy bioactivation was significantly correlated to
      CYP2J2 expression. Studies in HL-60 cells expressing CYP2J2 showed reduced cell
      viability when incubated with Cy (half maximal inhibitory concentration=3.6 mM).
      Inhibition of CYP2J2 using telmisartan reduced Cy bioactivation by 50% and
      improved cell survival. Cy incubated with recombinant CYP2J2 microsomes has
      resulted in apparent Km and Vmax values of 3.7-6.6 mM and 2.9-10.3
      pmol/(min.pmol) CYP, respectively. This is the first study demonstrating that
      CYP2J2 is equally important to CYP2B6 in Cy metabolism. The heart, intestine and
      urinary bladder express high levels of CYP2J2; local Cy bioactivation may explain
      Cy-treatment-related toxicities in these organs.

PMID- 25601762
TI  - Pharmacodynamic genome-wide association study identifies new responsive loci for
      glucocorticoid intervention in asthma.
AB  - Asthma is a chronic lung disease that has a high prevalence. The therapeutic
      intervention of this disease can be made more effective if genetic variability in
      patients' response to medications is implemented. However, a clear picture of the
      genetic architecture of asthma intervention response remains elusive. We
      conducted a genome-wide association study (GWAS) to identify drug response
      associated genes for asthma, in which 909 622 SNPs were genotyped for 120
      randomized participants who inhaled multiple doses of glucocorticoids. By
      integrating pharmacodynamic properties of drug reactions, we implemented a
      mechanistic model to analyze the GWAS data, enhancing the scope of inference
      about the genetic architecture of asthma intervention. Our pharmacodynamic model
      observed associations of genome-wide significance between dose-dependent response
      to inhaled glucocorticoids (measured as %FEV1) and five loci (P=5.315 * 10(-7) to
      3.924 * 10(-9)), many of which map to metabolic genes related to lung function
      and asthma risk. All significant SNPs detected indicate a recessive effect, at
      which the homozygotes for the mutant alleles drive variability in %FEV1.
      Significant associations were well replicated in three additional independent
      GWAS studies. Pooled together over these three trials, two SNPs, chr6 rs6924808
      and chr11 rs1353649, display an increased significance level (P=6.661 * 10(-16)
      and 5.670 * 10(-11)). Our study reveals a general picture of pharmacogenomic
      control for asthma intervention. The results obtained help to tailor an optimal
      dose for individual patients to treat asthma based on their genetic makeup.

PMID- 25601764
TI  - The importance of ligands for G protein-coupled receptor stability.
AB  - Traditionally, G protein-coupled receptor (GPCR) activity has been characterized
      by ligand properties including affinity (Ki), potency (IC50/EC50), efficacy
      (Emax), and kinetics (Kon/Koff). These properties are related to ligand residence
      time, a general index of drug-target interaction in vivo. Recent GPCR structure
      function breakthroughs have all required ligand stabilization of the receptor in
      some manner, highlighting the natural instability of these important cell surface
      receptors. This research has initiated a new era of discovery that highlights the
      importance of ligand-receptor interactions beyond the traditional mindset. We
      propose that receptor stability is related to receptor folding and residence in
      the cell membrane, affording a new dimension that should be considered when
      studying receptor function. 

PMID- 25601763
TI  - Recurrent Tako-Tsubo cardiomyopathy (TTC) in a pre-menopausal woman: late
      sequelae of a traumatic event?
AB  - BACKGROUND: "Tako-Tsubo cardiomyopathy" (TTC) is a syndrome characterized by left
      ventricular (LV) wall motion abnormalities, usually without coronary artery
      disease, mimicking the diagnosis of acute coronary syndrome. It most often
      affects post-menopausal women and TTC tends to run a benign course with very low
      rates of recurrence, complications or mortality. The condition is also called
      "stress-induced cardiomyopathy" because acute physical or emotional stress
      appears to be frequently related to its onset. The pathogenic role of premorbid
      or comorbid psychiatric illnesses has been discussed controversially. For the
      first time, we present a case of fourfold recurrent TTC with severe complications
      in a pre-menopausal woman. Furthermore, a long history of flaring posttraumatic
      stress symptoms anteceded the first event. CASE PRESENTATION: A 43-year old, pre
      menopausal Caucasian woman was hospitalized with symptoms of acute coronary
      syndrome. Clinical examination revealed hypokinetic wall motion in the apical
      ventricular region with no signs of coronary artery disease and diagnosis of TTC
      was established. She experienced recurrence three times within the following ten
      months, which led to thrombembolism and myocardial scarring among others. The
      circumstances of chronic distress were striking. 16 years ago she miscarried
      after having removed a myoma according to her doctor's suggestion. Since then,
      she has suffered from symptoms of posttraumatic distress which peaked annually at
      the day of abortion. Chronic distress became even more pronounced after the
      premature birth of a daughter some years later. The first event of TTC occurred
      after a family dispute about parenting. CONCLUSION: This is the first case report
      of fourfold TTC in a pre-menopausal woman. From somatic perspectives, the course
      of the disease with recurrences and complications underlines the fact that TTC is
      not entirely benign. Furthermore, it is the first case report of long lasting
      symptoms of traumatic stress anteceding TTC. Close connections between adrenergic
      signaling and late onset of clinical stress symptoms are well known in the
      psychopathology of traumatization. Although larger clinical trials are needed to
      elucidate possible interactions of premorbid psychiatric illnesses and TTC,
      cardiologists should be vigilant especially in cases of recurrent TTC.

PMID- 25601766
TI  - Asystole complicating acalculous cholecystitis, the "Cope's sign" revisited.

PMID- 25601767
TI  - Spin-glass behavior of a hierarchically-organized, hybrid microporous material,
      based on an extended framework of octanuclear iron-oxo units.
AB  - Inspired by the stepwise addition of octanuclear iron units into mammalian
      ferritin, a "stop-and-go" synthesis strategy was used to prepare two microporous
      (Langmuir surface area, 490 m(2) g(-1); effective pore size, 4-5 A) hierarchical
      materials {[Fe8(MU4-O)4(MU-pz)12Cl0.3(MU-O)1.85}n () and {[Fe8(MU4-O)4(MU-4-Me
      pz)12Cl0.4(MU-O)1.8}n (), which are new members of the EO2 family of polymeric
      materials (E = C, Si and Ge). The secondary building units (SBUs) E = [Fe8(MU4
      O)4(MU-4-R-pz)12] (Fe8) are nanoscale pseudo-spherical clusters, rather than
      single atoms, forming MU-oxo Fe-O-Fe linkages between Fe8-SBUs. The
      characteristic Fe-O-Fe asymmetric stretching mode in the infrared (IR) spectra of
      these compounds appearing at around 800 cm(-1) suggest the formation of
      approximately linear MU-oxo Fe-O-Fe linkages between Fe8-SBUs in and . We employ
      the concept of continuous random network (CRN) to describe for the first time the
      framework features of a Fe8-based amorphous materials, in which the average
      connecting numbers of each Fe8-cluster are ~3.7 and ~3.6 for and , respectively.
      (57)Fe-Mossbauer spectroscopic analysis provides insights to the intercluster
      connectivity of and on one hand and to their magnetic properties on the other,
      evident by a magnetic split sextet below 30 K. The combination of Mossbauer
      spectroscopy and magnetism measurements reveals a spin-glass behavior with Tg of
      ~30 K. The hierarchical porous materials and straddle the gap between metal
      oxides and metal-organic frameworks (MOFs). This study may open an alternative
      way for the development of multifunctional materials based on high nuclearity
      metal clusters. 

PMID- 25601765
TI  - Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia
      induced brain damage.
AB  - Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral
      ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim
      was to determine wether Sema3A functions as a vascular permeability factor and
      contributes to ischemic brain damage. Recombinant Sema3A injected intradermally
      to mouse skin, or stereotactically into the cerebral cortex, caused dose- and
      time-dependent increases in vascular permeability, with a degree comparable to
      that caused by injection of a known vascular permeability factor vascular
      endothelial growth factor receptors (VEGF). Application of Sema3A to cultured
      endothelial cells caused disorganization of F-actin stress fibre bundles and
      increased endothelial monolayer permeability, confirming Sema3A as a permeability
      factor. Sema3A-mediated F-actin changes in endothelial cells were through binding
      to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates
      Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA,
      alleviated Sema3A-induced F-actin disorganization, cellular morphology changes
      and endothelial permeability. Importantly, ablation of Sema3A expression,
      cerebrovascular permeability and brain damage were significantly reduced in
      response to transient middle cerebral artery occlusion (tMCAO) and in a mouse
      model of cerebral ischemia/haemorrhagic transformation. Together, these studies
      demonstrated that Sema3A is a key mediator of cerebrovascular permeability and
      contributes to brain damage caused by cerebral ischemia. 

PMID- 25601768
TI  - The natural history of renal functional decline in patients undergoing
      surveillance in the DISSRM registry.
AB  - OBJECTIVE: To describe the natural history of renal function in patients on
      active surveillance (AS) for small renal masses (SRM) in the Delayed Intervention
      and Surveillance for Small Renal Masses Registry. METHODS: Delayed Intervention
      and Surveillance for Small Renal Masses is a prospective, multi-institutional
      registry of patients with SRM (<= 4 cm) who choose intervention or AS. Of these,
      64 patients on AS had longitudinal serum creatinine (sCr) values and underwent
      analysis of estimated glomerular filtration rate (eGFR). eGFR was calculated
      using the Modification of Diet in Renal Disease formula. The Kidney Disease
      Outcomes Quality Initiative chronic kidney disease (CKD) classification was used
      to categorize patients' eGFR values. RESULTS: Median age was 74 (range: 34-88)
      years at onset of AS. Overall, 9% (6/64) of patients had CKD at baseline. Median
      initial tumor size was 2.1cm (range: 0.8-4.0). Median Charlson comorbidity index
      score was 4 (range: 0-8). Median baseline sCr was 1.0mg/dl (range: 0.4-2.1) and
      median baseline eGFR was 70.25 (range: 24.07-165.52). After a median follow-up of
      17 (range: 2-46) months, 64% of patients experienced a decrease in eGFR, with
      average yearly decrease in eGFR of 1.82 ml/min/1.73 m(2) (P = 0.092) and average
      yearly increase in sCr of 0.046 (P = 0.012). A total of 15 (24%) patients
      experienced an upstaging in classification of CKD. DISCUSSION: Nearly two-thirds
      of patients on AS experienced a decrease in eGFR and nearly one-fourth had
      upstaging of CKD classification. The annual eGFR decline experienced by patients
      on AS minimally exceeded the annual decline of 1.49 +/- 0.3 ml/min/1.73 m(2) that
      an individual who was 70 to 79 years of age can expect from aging alone. Further
      follow-up is necessary to assess this in a more definitive manner, but this trend
      should be considered when evaluating AS as an alternative to interventional
      therapies for SRM.

PMID- 25601769
TI  - Retrospective analysis of long-term outcome of chronic progressive neurological
      manifestations in Behcet's disease.
AB  - OBJECTIVES: Chronic progressive neuro-Behcet's disease (CPNBD) is characterized
      by progressive deterioration leading to disability and death. Although
      methotrexate has been found effective for CPNBD, its influences on the long-term
      outcome remain unclear. We therefore explored the effects of various treatments
      on the prognosis. METHODS: Thirty-seven patients, who met the international
      classification criteria for BD and developed chronic progressive neuropsychiatric
      manifestations after 1988, were followed up until October 2013. The effects of
      various treatments on prevention of death or severe disability of bedridden state
      were examined by Kaplan-Meier analysis and Cox's proportional hazard model.
      RESULTS: Twenty-eight of 37 patients with CPNBD (75.7%) received methotrexate.
      Among the 28 patients, none died and only 5 patients progressed to disability
      with bedridden state. By contrast, among the 9 patients without methotrexate, 5
      patients died and 3 patients progressed to bedridden state. Thus, methotrexate
      significantly improved the survival of patients with CPNBD (HR 0.0507, p=0.020)
      as well as reduced the rate of progression into bedridden state or death (HR
      0.2082, p=0.0126), but none of high doses of steroids, azathioprine or
      cyclophosphamide did. CONCLUSION: The results indicate that methotrexate, but not
      high doses of steroids, azathioprine or cyclophosphamide, is effective to prevent
      the progression of CPNBD.

PMID- 25601770
TI  - Clinical utility of triptans in the management of headache attributed to dural
      arteriovenous fistula involving the cavernous sinus.

PMID- 25601771
TI  - Pain: converging on LTP.

PMID- 25601772
TI  - Behavioural neuroscience: Swarming away from smells.

PMID- 25601773
TI  - Neurodegenerative disease: Restoring balance in Huntington disease.

PMID- 25601774
TI  - Neurodegenerative disease: Factoring in astrocytes.

PMID- 25601780
TI  - Spatial cognition in bats and rats: from sensory acquisition to multiscale maps
      and navigation.
AB  - Spatial orientation and navigation rely on the acquisition of several types of
      sensory information. This information is then transformed into a neural code for
      space in the hippocampal formation through the activity of place cells, grid
      cells and head-direction cells. These spatial representations, in turn, are
      thought to guide long-range navigation. But how the representations encoded by
      these different cell types are integrated in the brain to form a neural 'map and
      compass' is largely unknown. Here, we discuss this problem in the context of
      spatial navigation by bats and rats. We review the experimental findings and
      theoretical models that provide insight into the mechanisms that link sensory
      systems to spatial representations and to large-scale natural navigation. 

PMID- 25601781
TI  - Influence of atmospheric properties on detection of wood-warbler nocturnal flight
      calls.
AB  - Avian migration monitoring can take on many forms; however, monitoring active
      nocturnal migration of land birds is limited to a few techniques. Avian nocturnal
      flight calls are currently the only method for describing migrant composition at
      the species level. However, as this method develops, more information is needed
      to understand the sources of variation in call detection. Additionally, few
      studies examine how detection probabilities differ under varying atmospheric
      conditions. We use nocturnal flight call recordings from captive individuals to
      explore the dependence of flight call detection on atmospheric temperature and
      humidity. Height or distance from origin had the largest influence on call
      detection, while temperature and humidity also influenced detectability at higher
      altitudes. Because flight call detection varies with both atmospheric conditions
      and flight height, improved monitoring across time and space will require
      correction for these factors to generate standardized metrics of songbird
      migration. 

PMID- 25601782
TI  - Modeling the effects of climate on date palm scale (Parlatoria blanchardi)
      population dynamics during different phenological stages of life history under
      hot arid conditions.
AB  - The date palm scale (DPS) Parlatoria blanchardi is a serious pest due to the
      damage it inflicts on its host tree (Phoenix dactylifera). To develop an
      effective control against DPS in arid regions, it is essential to know its bio
      ecology including population dynamics and climatic factors influencing the
      duration and timing of life history and also the densities of different
      phenological stages (crawlers, first and second instars nymphs, adult males, and
      adult females). Monitoring of biological cycle and population dynamics of the
      pest were achieved through weekly counts of DPS densities on leaflets sampled at
      different position of date palm trees in an oasis of Ouargla region (Algerian
      Sahara Desert). Within this hyper-arid region, DPS established four generations
      per year, the most important was the spring generation. Two overlapping
      generations occurred in spring-early summer and two in autumn-early winter; these
      two pairs of generations were interspersed by two phases of high-mortality rates,
      the first corresponds to winter cold and the second refers to the extreme heat of
      summer. Statistical analysis of the effects of the studied climatic conditions
      (minimum, maximum and mean temperatures, precipitation, humidity, wind, rain
      days, and climatic indices) on the DPS densities at different phenological stages
      showed great variability from one stage to another. Among these, adult females
      were the most affected by climate factors. For the total DPS population, high
      values of minimum temperatures negatively affected population density, while high
      maximum temperatures, hygrometry, and De Martonne aridity index showed a positive
      influence.

PMID- 25601779
TI  - Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell
      microcircuits.
AB  - The adult mammalian cerebellar cortex is generally assumed to have a uniform
      cytoarchitecture. Differences in cerebellar function are thought to arise
      primarily through distinct patterns of input and output connectivity rather than
      as a result of variations in cortical microcircuitry. However, evidence from
      anatomical, physiological and genetic studies is increasingly challenging this
      orthodoxy, and there are now various lines of evidence indicating that the
      cerebellar cortex is not uniform. Here, we develop the hypothesis that regional
      differences in properties of cerebellar cortical microcircuits lead to important
      differences in information processing. 

PMID- 25601783
TI  - Oxidant/antioxidant status in lambs and sheep with liver and lung cystic
      echinococcosis diagnosed by ultrasonography and necropsy.
AB  - The aim of this study was to evaluate total antioxidant capacity (TAC), total
      oxidant status (TOS), and oxidative stress index (OSI) in sheep and lambs with
      cyctic eccinocoocosis (CE) diagnosed by ultrasonography and necropsy findings. A
      total of 9 sheep and 17 lambs with CE were used in this study and the findings
      were compared to those of 6 healthy control sheep. Ultrasonography were used for
      the diagnosis of CE in sheep and lambs, and necropsy was performed to check the
      presence of cysts in liver and lungs. Serum TOS and TAC were measured by a novel
      colorimetric method. The TOS-to-TAC ratios were also calculated as OSI values.
      Serum biochemical profiles were determined by conventional measurement methods as
      well. The mean values for TOS, TAC and OSI were significantly (p<0.001) lower in
      sheep and lambs with CE when compared with those of the control sheep, and they
      were also significantly lower in lambs with CE in comparison to the mean values
      obtained in sheep with CE. The levels of serum albumin, total cholesterol,
      creatinine, and triglycerides in lambs with CE were found out to decrease
      significantly (p<0.001) when compared with those of both sheep with EC and the
      control group. There were no significant differences between the groups in terms
      of other serum parameters. In addition, when clinically and some biochemical
      values were evaluated, CE was found to be more severe in lambs than in sheep. It
      was concluded that although common diagnostic cyst detection is performed by
      postmortem examination, ultrasonography could successfully be used in conjunction
      with serum biochemical profile detection and serum TOS, TAC and OSI measurements
      for diagnosis of cysts in liver and lungs of severely infected living sheep and
      lambs. Serum albumin, total cholesterol, creatinine, total protein and
      triglycerides might be used as indicators in sheep and particularly in lambs for
      the diagnosis of CE. 

PMID- 25601784
TI  - Where do we go from here? A comment on 'Emotional processing in a ten-session
      general psychiatric treatment for borderline personality disorder: a case study'.

PMID- 25601785
TI  - Molecular systems governing leaf growth: from genes to networks.
AB  - Arabidopsis leaf growth consists of a complex sequence of interconnected events
      involving cell division and cell expansion, and requiring multiple levels of
      genetic regulation. With classical genetics, numerous leaf growth regulators have
      been identified, but the picture is far from complete. With the recent advances
      made in quantitative phenotyping, the study of the quantitative, dynamic, and
      multifactorial features of leaf growth is now facilitated. The use of high
      throughput phenotyping technologies to study large numbers of natural accessions
      or mutants, or to screen for the effects of large sets of chemicals will allow
      for further identification of the additional players that constitute the leaf
      growth regulatory networks. Only a tight co-ordination between these numerous
      molecular players can support the formation of a functional organ. The
      connections between the components of the network and their dynamics can be
      further disentangled through gene-stacking approaches and ultimately through
      mathematical modelling. In this review, we describe these different approaches
      that should help to obtain a holistic image of the molecular regulation of organ
      growth which is of high interest in view of the increasing needs for plant
      derived products. 

PMID- 25601786
TI  - Ebola vaccine trials back on track.

PMID- 25601787
TI  - Drug-eluting stents--SORTed.

PMID- 25601788
TI  - Acute fulminant endophthalmitis complicating traditional lens couching.

PMID- 25601791
TI  - Proteome mining for drug target identification in Listeria monocytogenes strain
      EGD-e and structure-based virtual screening of a candidate drug target penicillin
      binding protein 4.
AB  - We used a combination of in-silico approaches to identify 168 promising drug
      targets in the proteome of a multidrug-resistant Listeria monocytogenes strain;
      of these, one (PBP4) was particularly promising. Virtual screening using it,
      followed by reverse docking, revealed four compounds namely NCI524121, CAP332797,
      NCI524136 and ZINC00518462 as good multi-target leads. 

PMID- 25601790
TI  - Methodological issues in the quantification of subgingival microorganisms using
      the checkerboard technique.
AB  - The reproducibility and reliability of quantitative microbiological assessments
      using the DNA-DNA hybridization "checkerboard method" (CKB) were assessed. The
      data originated from 180 chronic periodontitis patients, who were enrolled in a
      clinical trial and sampled at baseline, and 3 and 12m post-therapy. The samples
      were divided into two portions allowing evaluation of reproducibility. In total,
      531 samples were analyzed in a first run, using standard bacterial preparations
      of cells and 513 samples were accessible for analysis in the second, using
      standards based on purified DNA from the species. The microbial probe panel
      consisted of periodontitis marker bacteria as well as non-oral microorganisms.
      Three different ways of quantifying and presenting data; the visual scoring
      method, VSM, the standard curve method, SCM, and the percent method, PM, were
      compared. The second set of analyses based on the use of standard preparations of
      pure DNA was shown to be more consistent than the first set using standards based
      on cells, while the effect of storage time per se up to 2.5y seemed to be
      marginal. The best reproducibility was found for Tannerella forsythia,
      irrespective of quantification technique (Spearman's rho=0.587, Pearson's
      r>=0.540). The percent method (PM) based on percent of High Standard (10(6)
      cells) was more reliable than SCM based on a linear calibration of the High
      Standard and a Low Standard (10(5) cells). It was concluded that the
      reproducibility of the CBK method varied between different bacteria. High quality
      and pure specific DNA whole genomic probes and standards may have a stronger
      impact on the precision of the data than storage time and conditions. 

PMID- 25601792
TI  - Identification and validation of polymorphic microsatellite loci for the analysis
      of Phytophthora nicotianae populations.
AB  - A large number of SSR loci were screened in the genomic assemblies of 14
      different isolates of Phytophthora nicotianae and primers were developed for
      amplification of 17 markers distributed among different contigs. These loci were
      highly polymorphic and amplified from genetically distant isolates of the
      pathogen. Among these, nine were further validated using a multiplexed genotyping
      assay with differentially labeled primers (FAM or HEX) to allow for duplex PCR
      amplification. The use of reverse primers with a 5' PIG tail was important to
      increase the quality and reliability of the analyses. A total of 46 alleles were
      detected in 5 tester isolates of P. nicotianae representing the breadth of
      diversity in the species. Furthermore, a high incidence of heterozygosity was
      determined with two alleles detected in 67% of the primer/isolate combinations.
      Three different alleles where detected for a single locus/isolate combination,
      indicating variation in ploidy. These markers represent a valuable new tool for
      the characterization of populations of P. nicotianae. 

PMID- 25601789
TI  - Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting
      biodegradable-polymer-coated stent in unselected patients undergoing percutaneous
      coronary intervention (SORT OUT VI): a randomised non-inferiority trial.
AB  - BACKGROUND: New-generation drug-eluting coronary stents have reduced the risk of
      coronary events, especially in patients with complex disease or lesions. To what
      extent different stent platforms, polymers, and antiproliferative drugs affect
      outcomes, however, is unclear. We investigated the safety and efficacy of a third
      generation stent by comparing a highly biocompatible durable-polymer-coated
      zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting
      stent. METHODS: This open-label, randomised, multicentre, non-inferiority trial
      was done at three sites across western Denmark. All patients who presented with
      stable coronary artery disease or acute coronary syndromes and at least one
      coronary artery lesion (more than 50% stenosis) from March, 2011, to August,
      2012, were assessed for eligibility. Patients were randomly assigned in a 1:1
      ratio to receive either the durable-polymer zotarolimus-eluting stent or the
      biodegradable-polymer biolimus-eluting stent. The primary endpoint was a
      composite of safety (cardiac death and myocardial infarction not clearly
      attributable to a non-target lesion) and efficacy (target-lesion
      revascularisation) at 12 months, analysed by intention to treat. The trial was
      powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent
      compared with the biodegradable-polymer biolimus-eluting stent with a
      predetermined non-inferiority margin of 0.025. This trial is registered with
      ClinicalTrials.gov, number NCT01956448. FINDINGS: Of 7103 screened, 1502 patients
      with 1883 lesions were assigned to receive the durable-polymer zotarolimus
      eluting stent and 1497 patients with 1791 lesions to receive the biodegradable
      polymer biolimus-eluting stent. 79 (5.3%) and 75 (5.0%) patients, respectively,
      met the primary endpoint (absolute risk difference 0.0025, upper limit of one
      sided 95% CI 0.016%; p=0.004). The individual components of the primary endpoint
      did not differ significantly between stent types at 12 months. INTERPRETATION:
      The durable-polymer-coated zotarolimus-eluting stent was non-inferior to the
      biodegradable-polymer-coated biolimus-eluting stent in unselected patients.
      FUNDING: Medtronic Cardiovascular and Biosensors Interventional Technologies.

PMID- 25601793
TI  - Influence of Benzannulation on Metal Coordination Geometries: Synthesis and
      Structural Characterization of Tris(2-mercapto-1-methylbenzimidazolyl)hydroborato
      Cadmium Bromide, {[TmMeBenz]Cd(MU-Br)}2.
AB  - The tris(2-mercapto-1-methylbenzimidazolyl)hydroborato cadmium complex,
      {[TmMeBenz]Cd(MU-Br)}2, may be synthesized via the reaction of [TmMeBenz]K with
      CdBr2. X-ray diffraction demonstrates that {[TmMeBenz]Cd(MU-Br)}2 exists as a
      dimer, which is in marked contrast to the monomeric structure of the non
      benzannulated counterpart, [TmMe]CdBr, and thereby demonstrates that
      benzannulation of tris(2-mercapto-1-methylbenzimidazolyl)hydroborato ligands can
      have a distinct impact on the molecular structure of their metal complexes. In
      accord with this observation, density functional theory calculations indicate
      that the benzannulated dimers, {[TmMeBenz]Cd(MU-X)}2 (X = Cl, Br, I), are more
      stable with respect to dissociation than are their non-benzannulated
      counterparts, {[TmMe]Cd(MU-X)}2. Furthermore, the calculations also indicate that
      the stability of the dimer depends on the nature of X, such that the dimer
      becomes more stable in the sequence I < Br < Cl.

PMID- 25601794
TI  - Surface modification of tri-calcium phosphate nanoparticles by DOPE and/or anti
      E6 antibody to enhance uptake of antisense of E6 mRNA.
AB  - The main aim of this study was to evaluate the uptake of E6 mRNA antisense into
      cervical cancer cells, induced by human papilloma virus (HPV). In this study, the
      carrier of the antisense was tri-calcium phosphate nanoparticles (TCP NPs)
      conjugated with dioleoyl phosphatidyl ethanolamine (DOPE) and/or anti-E6
      antibody. At first, TCP NPs were synthesized, coated with carboxy-polyethylene
      glycol, and then conjugated with anti-E6 antibody and/or DOPE by carbodiimide
      cross-linker. Then, a single stranded DNA, which was complementary (antisense) of
      E6 mRNA, was attached to each one. Finally, the uptake of conjugated and
      unconjugated TCP NPs into HelaS3 cells was separately evaluated by Fourier
      transform infrared spectroscopy, optical microscopy, and fluorescent microscopy.
      Also, the cytotoxicity of these carriers was measured by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Overall, 4 types of TCP NPs
      were used in this study, including 1) TCP NPs conjugated with DOPE (TCP
      NPs/DOPE), 2) TCP NPs conjugated with DOPE and antibody (TCP NPs/DOPE/Anti-E6
      Ab), 3) TCP NPs conjugated with antibody (TCP NPs/Anti-E6 Ab), and 4) TCP NPs
      which not conjugated with DOPE and antibody (unconjugated TCP NPs). Uptake tests
      showed that although all types of TCP NPs could transfer antisense of E6 mRNA
      into HelaS3 cells, TCP NPs/DOPE and TCP NPs/DOPE/Anti-E6 Ab had more uptake than
      TCP NPs/Anti-E6 Ab and unconjugated TCP NPs. Moreover, MTT assay showed that TCP
      NPs/DOPE was more toxic than TCP NPs/DOPE/Anti-E6 Ab, TCP NPs/Anti-E6 Ab, and
      unconjugated TCP NPs. It can be concluded that TCP NPs/DOPE/Anti-E6 Ab is a good
      choice for oligonucleotide delivery, because of higher uptake and less toxicity,
      compared with other formulations. 

PMID- 25601795
TI  - Cardiorespiratory fitness and cognitive function in midlife: neuroprotection or
      neuroselection?
AB  - OBJECTIVE: A study was undertaken to determine whether better cognitive
      functioning at midlife among more physically fit individuals reflects
      neuroprotection, by which fitness protects against age-related cognitive decline,
      or neuroselection, by which children with higher cognitive functioning select
      more active lifestyles. METHODS: Children in the Dunedin Longitudinal Study (N =
      1,037) completed the Wechsler Intelligence Scales and the Trail Making, Rey
      Delayed Recall, and Grooved Pegboard tasks as children and again at midlife (age
      = 38 years). Adult cardiorespiratory fitness was assessed using a submaximal
      exercise test to estimate maximum oxygen consumption adjusted for body weight in
      milliliters/minute/kilogram. We tested whether more fit individuals had better
      cognitive functioning than their less fit counterparts (which could be consistent
      with neuroprotection), and whether better childhood cognitive functioning
      predisposed to better adult cardiorespiratory fitness (neuroselection). Finally,
      we examined possible mechanisms of neuroselection. RESULTS: Participants with
      better cardiorespiratory fitness had higher cognitive test scores at midlife.
      However, fitness-associated advantages in cognitive functioning were already
      present in childhood. After accounting for childhood baseline performance on the
      same cognitive tests, there was no association between cardiorespiratory fitness
      and midlife cognitive functioning. Socioeconomic and health advantages in
      childhood and healthier lifestyles during young adulthood explained most of the
      association between childhood cognitive functioning and adult cardiorespiratory
      fitness. INTERPRETATION: We found no evidence for a neuroprotective effect of
      cardiorespiratory fitness as of midlife. Instead, children with better cognitive
      functioning are selecting healthier lives. Fitness interventions may enhance
      cognitive functioning. However, observational and experimental studies testing
      neuroprotective effects of physical fitness should consider confounding by
      neuroselection.

PMID- 25601797
TI  - A critical appraisal of the updated 2014 Nice Pulmonary Hypertension
      Classification System.
AB  - In 2013, the Fifth World Symposium on Pulmonary Hypertension (PH) was held in
      Nice, France. This meeting has been held every 5 years since the Second World
      Symposium in 1998, when the modern-day classification system of PH was initially
      conceived. PH is a pathophysiologic state of the pulmonary circulation
      characterized by an increased mean pulmonary artery pressure >= 25 mm Hg at rest,
      and can be the consequence of a variety of distinct disease entities. The
      rationale of a classification system for PH was to group together disease
      entities that share similar pathomechanisms, clinical presentation, and
      therapeutic approaches. Refinements of the classification system have been made
      at each subsequent World Symposium, reflecting the ongoing research and new
      knowledge acquired in the science of PH. We provide an update of the recent
      changes made to the PH classification system from the Nice meeting. 

PMID- 25601796
TI  - Dynamics of CYP51: implications for function and inhibitor design.
AB  - Sterol 14alpha-demethylase (cytochrome P450 family 51 (CYP51)) is an essential
      enzyme occurring in all biological kingdoms. In eukaryotes, it is located in the
      membrane of the endoplasmic reticulum. Selective inhibitors of trypanosomal
      CYP51s that do not affect the human CYP51 have been discovered in vitro and found
      to cure acute and chronic mouse Chagas disease without severe side effects in
      vivo. Crystal structures indicate that CYP51 may be more rigid than most CYPs,
      and it has been proposed that this property may facilitate antiparasitic drug
      design. Therefore, to investigate the dynamics of trypanosomal CYP51, we built a
      model of membrane-bound Trypanosoma brucei CYP51 and then performed molecular
      dynamics simulations of T. brucei CYP51 in membrane-bound and soluble forms. We
      compared the dynamics of T. brucei CYP51 with those of human CYP51, CYP2C9, and
      CYP2E1. In the simulations, the CYP51s display low mobility in the buried active
      site although overall mobility is similar in all the CYPs studied. The
      simulations suggest that in CYP51, pathway 2f serves as the major ligand access
      tunnel, and both pathways 2f (leading to membrane) and S (leading to solvent) can
      serve as ligand egress tunnels. Compared with the other CYPs, the residues at the
      entrance of the ligand access tunnels in CYP51 have higher mobility that may be
      necessary to facilitate the passage of its large sterol ligands. The water (W)
      tunnel is accessible to solvent during most of the simulations of CYP51, but its
      width is affected by the conformations of the heme's two propionate groups. These
      differ from those observed in the other CYPs studied because of differences in
      their hydrogen-bonding network. Our simulations give insights into the dynamics
      of CYP51 that complement the available experimental data and have implications
      for drug design against CYP51 enzymes.

PMID- 25601798
TI  - Breast milk from women living near Lake Malawi is high in docosahexaenoic acid
      and arachidonic acid.
AB  - Adequate long-chain polyunsaturated fatty acid (LCPUFA) intake is critical during
      the fetal and infant periods. We quantified fatty acid content of breast milk
      (n=718) and plasma from six month old infants (n=412) in southern Malawi, and in
      usipa (n=3), a small dried fish from Lake Malawi. Compared to global norms,
      Malawian breast milk fatty acid content (% of total fatty acids) was well above
      average levels of arachidonic acid [ARA] (0.69% vs. 0.47%) and docosahexaenoic
      acid [DHA] (0.73% vs. 0.32%). Average Malawian infant plasma ARA (7.5%) and DHA
      (3.8%) levels were comparable to those reported in infants consuming breast milk
      with similar fatty acid content. The amounts (mg) of DHA, EPA and ARA provided by
      a 3 oz (85 g) portion of dried usipa (1439, 659 and 360, respectively) are
      considerably higher than those for dried salmon. Usipa may be an important source
      of LCPUFA for populations in this region.

PMID- 25601799
TI  - Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine.
AB  - In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached
      pandemic status and was soon after detected in pigs worldwide. The objective of
      this study was to evaluate whether differences in the HA protein can affect
      pathogenicity and antigenicity of H1N1pdm09 in swine. We compared lung pathology,
      viral replication and shedding and the antigenic relationships of four wild-type
      H1N1pdm09 viruses in pigs: one human (CA/09) and three isolated in swine after
      the pandemic (IL/09, IL/10, and MN/10). The swine strains were selected based
      upon unique amino acid substitutions in the HA protein. All selected viruses
      resulted in mild disease and viral shedding through nasal and oral fluids,
      however, viral replication and the degree of pathology varied between the
      isolates. A/Swine/IL/5265/2010 (IL/10), with substitutions I120M, S146G, S186P,
      V252M, had lower viral titers in the lungs and nasal secretions and fewer lung
      lesions. The other two swine viruses caused respiratory pathology and replicated
      to titers similar to the human CA/09, although MN/10 (with mutations D45Y, K304E,
      A425S) had lower nasal shedding. Swine-adapted H1N1pdm09 have zoonotic potential,
      and have reassorted with other co-circulating swine viruses, influencing the
      evolution of IAV in swine globally. Further, our results suggest that amino acid
      changes in the HA gene have the potential to alter the virulence of H1N1pdm09 in
      swine. Importantly, the limited clinical signs in pigs could result in continued
      circulation of these viruses with other endemic swine IAVs providing
      opportunities for reassortment. 

PMID- 25601801
TI  - Previous infection of sows with a "mild" strain of porcine epidemic diarrhea
      virus confers protection against infection with a "severe" strain.
AB  - Porcine epidemic diarrhea virus (PEDv) infected approximately 50% of the US swine
      breeding herds from July 2013 to July 2014 as estimated by the Swine Health
      Monitoring Project. In the absence of effective vaccines or standard control
      protocols, there is an urgent need for evidence of cross-protective immune
      countermeasures. Here, we evaluated the response of 3-day-old piglets born to
      sows exposed seven months earlier to a mild strain of PEDv to challenge with a
      virulent PEDv isolate. Piglet survival to one week of age was 100% compared to
      67% in piglets born to sows not previously exposed, and morbidity was 43%
      compared to 100%, respectively. At necropsy at 7 days of age, the PEDv Ct value
      was 23.6 (range 16.6-30.6) in intestinal contents, compared to 17.2 (range 15.9
      18.5) (p<0.06) in litters from sows with no previous exposure to PEDv. The
      findings indicated that durable lactogenic immunity was present in sows
      previously exposed to a mild strain of PEDv and this immunity induced cross
      protection to representative virulent PEDv. Thus, a naturally attenuated form of
      PEDv provided significant passive immune protection for seven months against
      piglet challenge with virulent PEDv. 

PMID- 25601800
TI  - Identification of an outer membrane protein of Fusobacterium necrophorum subsp.
      necrophorum that binds with high affinity to bovine endothelial cells.
AB  - Fusobacterium necrophorum, a Gram-negative anaerobe, is the primary etiologic
      agent of liver abscesses in cattle. There are two subspecies; subsp. necrophorum
      and subsp. funduliforme, which differ in morphological, biochemical, molecular
      characteristics, and virulence. The subsp. necrophorum, which is more virulent,
      occurs more frequently in liver abscesses than the subsp. funduliforme. Bacterial
      adhesion to the host cell surface is critical to the pathogenesis of several
      bacterial infections, and in F. necrophorum, outer membrane proteins (OMP) have
      been shown to mediate adhesion to bovine endothelial cells. The objective of this
      study was to identify potential adhesins that are involved in adhesion of F.
      necrophorum subsp. necrophorum to the host cells. An OMP of 42.4 kDa, which binds
      with high affinity to the bovine endothelial cells and is recognized by the sera
      from cattle with liver abscesses, was identified. N-terminal sequencing of the
      protein showed 96% homology to the FomA protein of F. nucleatum. The PCR analysis
      showed that this fomA gene was present in several strains of subsp. necrophorum,
      subsp. funduliforme of bovine and subsp. funduliforme of human origin. The
      purified native and recombinantly expressed protein when preincubated with the
      endothelial cells, prevented the attachment of subsp. necrophorum significantly.
      In addition, the polyclonal antibody produced against the protein prevented the
      binding of subsp. necrophorum to bovine endothelial cells.

PMID- 25601803
TI  - Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for
      Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable
      Polymeric Nanoparticles.
AB  - A novel polyphosphoester (PPE) with vinyl ether side chain functionality was
      developed as a versatile template for postpolymerization modifications, and its
      degradability and biocompatibility were evaluated. An organo-catalyzed ring
      opening polymerization of ethylene glycol vinyl ether-pendant cyclic
      phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl
      ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was
      coupled with hydroxyl- or thiol-containing model small molecules via three
      different types of conjugation chemistries-thiol-ene "click" reaction,
      acetalization, or thio-acetalization reaction-to afford modified polymers that
      accommodated either stable thio-ether or hydrolytically labile acetal or thio
      acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and
      PEVEP formed well-defined micelles with a narrow and monomodal size distribution
      in water, as confirmed by dynamic light scattering (DLS), transmission electron
      microscopy, and atomic force microscopy. The stability of the micelles and the
      hydrolytic degradability of the backbone and side chains of the PEVEP block
      segment were assessed by DLS and nuclear magnetic resonance spectroscopy (1H and
      31P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and
      at temperatures of 25 and 37  degrees C. The hydrolytic degradation products of
      the PEVEP segments of the block copolymers were then identified by electrospray
      ionization, gas chromatography, and matrix-assisted laser desorption/ionization
      mass spectrometry. The parent micelles and their degradation products were found
      to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW
      264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells.

PMID- 25601804
TI  - Prevention of type 2 diabetes - where is the evidence?

PMID- 25601802
TI  - Cognitive control of gaze in bipolar disorder and schizophrenia.
AB  - The objective of the present study was to compare two components of executive
      functioning, response monitoring and inhibition, in bipolar disorder (BP) and
      schizophrenia (SZ). The saccadic countermanding task is a translational paradigm
      optimized for detecting subtle abnormalities in response monitoring and response
      inhibition. We have previously reported countermanding performance abnormalities
      in SZ, but the degree to which these impairments are shared by other psychotic
      disorders is unknown. 18 BP, 17 SZ, and 16 demographically matched healthy
      controls (HC) participated in a saccadic countermanding task. Performance on the
      countermanding task is approximated as a race between movement generation and
      inhibition processes; this model provides an estimate of the time needed to
      cancel a planned movement. Response monitoring was assessed by the reaction time
      (RT) adjustments based on trial history. Like SZ patients, BP patients needed
      more time to cancel a planned movement. The two patient groups had equivalent
      inhibition efficiency. On trial history-based RT adjustments, however, we found a
      trend towards exaggerated trial history-based slowing in SZ compared to BP.
      Findings have implications for understanding the neurobiology of cognitive
      control, for defining the etiological overlap between schizophrenia and bipolar
      disorder, and for developing pharmacological treatments of cognitive impairments.

PMID- 25601805
TI  - Continuing progress in the priority health areas: actions for Member States and
      WHO.

PMID- 25601806
TI  - Confidentiality, informed consent and children's participation in the Saudi
      biobank governance: a comparative study.
AB  - The growth of research biobanks has created many new ethical challenges
      worldwide. This article outlines and discusses key issues in the governance of
      Saudi Biobank, a newly established national biobank in Saudi Arabia launched in
      2014. The Saudi Biobank project includes human biological samples from
      participants aged 10-70 years and aims to conduct an extensive study on the
      influence of genes, environment and lifestyle in common diseases. We examined the
      strengths and weaknesses of Saudi Biobank's governance as well as the
      similarities and differences with 4 other biobanks (in the United Kingdom,
      Iceland, Estonia and Canada). Three different ethical issues are discussed in
      detail: confidentiality, informed consent and children's participation in
      research. We evaluated these issues in relation to international ethical
      guidelines and Islamic law. The insights gained may be useful in developing
      national biobanking regulations in other Islamic countries, particularly in
      countries of the Eastern Mediterranean Region. 

PMID- 25601807
TI  - Adjustment factors to per capita health-care indicators in countries with
      expatriate male-majority populations.
AB  - From 2000 to 2010, the population in the Gulf Cooperation Council (GCC) countries
      underwent an increase of 53%, compared with an average global increase of 13%.
      The rates varied by country, ranging from 23% in Oman to 198% in Qatar. The main
      driving force for this sharp increase in population was the high demand for
      immigrant labour. The aim of this study was to adjust the population in the GCC
      countries in order to ensure that the comparisons of health-care key performance
      indicators with other countries account for the composition of the populations.
      The conclusion of the study was that adjusting the population in the GCC is
      instrumental for determining health spending and health outcomes, and that
      inaccurate forecasting would result in serious overestimation of the need for GCC
      countries to invest in the health-care sector. Policy-makers can utilize the
      population models in this study to accurately plan for health-care delivery. 

PMID- 25601808
TI  - Household food insecurity in the Islamic Republic of Iran: a systematic review
      and meta-analysis.
AB  - Using a systematic review of all available studies between 1991 and 2011, the
      prevalence of food insecurity in the Islamic Republic of Iran was estimated.
      After document evaluation and data aggregation, studies were analysed in separate
      categories based on the methods used: dietary recall, household
      income/expenditure or experiential/perception-based surveys. Meta-analysis of
      dietary-recall studies showed small non-significant increases between 1994 and
      2004 in the prevalence of mild (from 8.8% to 9.3%) and moderate food insecurity
      (from 5.4% to 5.6%). Severe food insecurity was 3.8% and 3.7% in 1994 and 2004
      respectively. Prevalence of food insecurity (moderate to severe) based on
      household income/expenditure surveys was consistently reported to be 10%. A
      separate meta-analysis of experiential/perception-based studies revealed rates of
      mild, moderate and severe food insecurity of 28.6%, 14.9% and 6.0% respectively.
      By combining study results in this manner makes it possible to come up with more
      realistic estimates for evidence-informed policy-making, until development of a
      national food insecurity surveillance system. 

PMID- 25601810
TI  - Adverse health effects of spousal violence among women attending Saudi Arabian
      primary health-care clinics.
AB  - This study aimed to investigate the frequency of spousal violence among Saudi
      women and document the related health effects and injuries, as well as their
      attitudes to gender and violence. Structured interviews were conducted with 200
      ever-married women recruited from primary-care centres in Jeddah. Nearly half of
      the surveyed women (44.5%) reported ever experiencing physical violence from
      their spouse. Although 37 women (18.5%) had received violence-related injuries,
      only 6.5% had reported these injuries to a health-care provider. Victims of
      spousal violence had poor perceptions of their overall health, and reported pain
      or discomfort, antidepressant use and suicidal thoughts. Women mostly disagreed
      with the presented justifications for wife-beating. However, the association
      between gender attitudes and spousal violence was not significant. The results of
      this study support calls for integration of education about partner violence into
      health-care curricula to enhance the access and quality of services. 

PMID- 25601809
TI  - Determinants of consultation, diagnosis and treatment delays among new smear
      positive pulmonary tuberculosis patients in Morocco: a cross-sectional study.
AB  - We conducted a cross-sectional survey in 2012 in 12 selected provinces and
      prefectures in Morocco to determine consultation delay (patient delay), diagnosis
      delay and treatment delay (health system delays), and factors relating to these
      delays. The sample included 250 eligible and consenting newly diagnosed
      smearpositive pulmonary tuberculosis patients who were interviewed at the time of
      their registration within Diagnosis of Tuberculosis and Respiratory Diseases
      Reference Centers (CDTMR) or Integrated Health Centers (CSI) using a pretested
      and structured questionnaire. The median total delay was 46 days [inter-quartile
      interval (IQI) = 29-84 days]. Patient delay (median = 20; IQI = 8-47 days) was
      higher than health system delay (median=15; IIQ = 7-35 days). Being illiterate,
      thinking symptoms will disappear by themselves; having financial constraints and
      feeling fear of diagnosis or social isolation were associated with patient delay.
      Consulting first in the private sector or having 3 or more consultations before
      diagnosis was associated with health system delay. 

PMID- 25601811
TI  - Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate
      dehydrogenase deficiency among Arab migrating nomad children, southern Islamic
      Republic of Iran.
AB  - This study investigated the prevalence of iron-deficiency anaemia, glucose-6
      phosphate dehydrogenase (G6PD) deficiency and beta-thalassaemia trait among Arab
      migrating nomad children in southern Islamic Republic of Iran. Blood samples were
      analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low
      serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females
      and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low
      serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had
      HbA2 >= 3.5 g/dL, indicating beta-thalassaemia trait (10.8% in females and 7.8%
      in males). Mean serum iron, serum ferritin and total iron binding capacity were
      similar in males and females. Serum ferritin index was as accurate as Hb index in
      the diagnosis of iron-deficiency anaemia. A high prevalence of beta-thalassaemia
      trait was the major potential risk factor in this population. 

PMID- 25601812
TI  - Oral health status of 12-year-old male schoolchildren in Medina, Saudi Arabia.
AB  - Studies from Saudi Arabia have reported that the prevalence of dental caries
      among children is relatively high compared with other developing countries The
      aim was to determine the oral hygiene status and significant caries (SiC) index
      of 12-year-old males in Medina . In a cross-sectional, analytical study 360
      students participated from 4 boys' schools. Dental caries, plaque, gingivitis,
      fluorosis and malocclusion were recorded using standard methods and indices. The
      mean DMFT score was 1.53 (SD 1.88). Caries prevalence was low (57.2%) but the
      mean SiC index was relatively high [3.63 (SD 1.66)]. The prevalences of plaque
      and gingivitis were high (82.8% and 70.8% respectively). Lower molars had the
      highest rate of caries. No children presented with dental fluorosis and 82.5% had
      a class I jaw relationship. Oral hygiene awareness programmes at schools,
      together with brushing and flossing programmes, are recommended in order to
      maintain and improve the oral health of young children in Medina. 

PMID- 25601814
TI  - Regional committee decisions.

PMID- 25601813
TI  - Pattern of beverage intake and milk and dairy products sufficiency among high
      school students in Kuwait.
AB  - High consumption of soft drinks has been associated with lower intakes of milk
      and calcium-rich foods and higher body mass index (BMI). This study aimed to
      explore the pattern of beverage intake among Kuwaiti high-school students. A
      questionnaire on knowledge, attitudes and practices concerning beverages and milk
      and dairy products intake was completed by 190 Kuwaiti students aged 16-18 years
      and BMI was calculated for 181 of them. Intake of sweetened carbonated beverages
      and to a lesser extent packaged fruit juices affected the sufficiency of milk and
      dairy products intake among the sample of high-school students in Kuwait.
      Although BMI was not related to milk and dairy insufficiency, more of the
      overweight and obese students displayed incorrect practices. Nutritional
      education of high-school students on the importance of milk and dairy products as
      well as the hazards of excess sweetened carbonated beverages and packaged juice
      is recommended to prevent the obesity epidemic prevailing in Kuwait. 

PMID- 25601815
TI  - Emergency preparedness and response.

PMID- 25601816
TI  - WHO events addressing public health priorities.

PMID- 25601817
TI  - Bone marrow mononuclear cell therapy for acute myocardial infarction: we know
      what we want, but we just don't know how yet.

PMID- 25601818
TI  - Facile syntheses of functionalized toll-like receptor 7 agonists.
AB  - Protein conjugates of toll-like receptor 7 agonists have been shown to elicit
      powerful immune responses. In order to facilitate our studies in this area our
      group has developed efficient syntheses for a number of functionalized
      derivatives that retain immune stimulatory activity.

PMID- 25601819
TI  - Somali Immigrant New Mothers' Childbirth Experiences in Minnesota.
AB  - PURPOSE: To explore Somali immigrant new mothers' experience of childbirth in
      Minnesota. DESIGN: The ethnonursing research method was used. Semistructured
      interviews with 12 immigrant Somali mothers in a Midwestern metropolitan area
      were conducted. Analysis of the data followed Leininger and McFarland's four
      phase ethnonursing data analysis guide. RESULTS: Six themes were identified in
      relation to Somali immigrant new mothers' experience of childbirth in the United
      States: the limitations of support due to separation from family, the importance
      of cultural and religious beliefs and practices, the desired relationships with
      nurses, the fear of Cesarean section, the value of education, and views on
      postpartum blues/depression. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Nurses
      should develop trusting relationships with Somali mothers and facilitate cultural
      and religious practices. Information regarding support resources in the community
      should be provided to Somali mothers.

PMID- 25601820
TI  - President's message: Reducing health disparities: transcultural nurses leading
      the way.

PMID- 25601821
TI  - The Role of Stress Exposure and Family Functioning in Internalizing Outcomes of
      Urban Families.
AB  - Although research suggests that stress exposure and family functioning are
      associated with internalizing problems in adolescents and caregivers,
      surprisingly few studies have investigated the mechanisms that underlie this
      association. To determine whether family functioning buffers the development of
      internalizing problems in stress-exposed families, we assessed the relation
      between stress exposure, family functioning, and internalizing symptoms among a
      large sample of inner-city male youth and their caregivers living in poverty
      across five waves of data collection. We hypothesized that stress exposure and
      family functioning would predict development of subsequent youth and caregiver
      internalizing problems and that family functioning would moderate this relation,
      with higher functioning families demonstrating greater resiliency to stress
      exposure. We used a longitudinal, prospective design to evaluate whether family
      functioning (assessed at waves one through four) activated or buffered the
      effects of stress exposure (assessed at wave one) on subsequent internalizing
      symptoms (assessed at waves four and five). Stress from Developmental Transitions
      and family functioning were significant predictors of depressive symptoms and
      anxiety in youth; however, family functioning did not moderate the relation.
      Family functioning mediated the relation between stress from Daily Hassles and
      internalizing outcomes suggesting that poor parenting practices, low structure,
      and low emotional cohesion activate depression and anxiety in youth exposed to
      chronic and frequent everyday stressors. Surprisingly, only family functioning
      predicted depressive symptoms in caregivers. Results validate the use of a
      comprehensive, multi-informant assessment of stress when investigating
      internalizing outcomes in youth and support using family-based interventions in
      the treatment and prevention of internalizing.

PMID- 25601822
TI  - High compliance vascular grafts based on semi-interpenetrating networks.
AB  - Current synthetic vascular grafts have poor patency rates in small diameter
      applications (<6 mm) due to intimal hyperplasia arising from a compliance
      mismatch between the graft and native vasculature. Enormous efforts have focused
      on improving biomechanical properties; however, polymeric grafts are often
      constrained by an inverse relationship between burst pressure and compliance. We
      have developed a new, semi-interpenetrating network (semi-IPN) approach to
      improve compliance without sacrificing burst pressure. The effects of heat
      treatment on graft morphology, fiber architecture, and resultant biomechanical
      properties are presented. In addition, biomechanical properties after
      equilibration at physiological temperature were investigated in relation to
      polyurethane microstructure to better predict in vivo performance. Compliance
      values as high as 9.2 +/- 2.7 %/mmHg x 10-4 were observed for the semi-IPN graft
      while also maintaining high burst pressure, 1780 +/- 230 mm Hg. The high
      compliance of these heat-treated poly(carbonate urethane) (PCU) and semi-IPN
      grafts is expected to improve long-term patency rates beyond even saphenous vein
      autografts by preventing intimal hyperplasia. The fundamental structure-property
      relationships gained from this work may also be utilized to advance biomedical
      device designs based on thermoplastic polyurethanes.

PMID- 25601823
TI  - The role of membrane acid/base transporters and carbonic anhydrases for cellular
      pH and metabolic processes.

PMID- 25601824
TI  - Cognitive, behavioral, and autonomic correlates of mind wandering and
      perseverative cognition in major depression.
AB  - Autonomic dysregulation has been hypothesized to play a role in the relationships
      between psychopathology and cardiovascular risk. An important transdiagnostic
      factor that has been associated with autonomic dysfunction is perseverative
      cognition (PC), mainly present in Major Depressive Disorder (MDD) in the form of
      rumination. As the ability to adaptively let our mind wander without ruminating
      is critical to mental health, this study aimed to examine the autonomic
      concomitants of functional vs. dysfunctional intrusive thoughts in MDD.
      Ambulatory heart rate (HR) and variability (HRV) of 18 MDD subjects and 18
      healthy controls were recorded for 24 h. Approximately every 30 min during waking
      hours subjects reported their ongoing thoughts and moods using electronic
      diaries. Random regression models were performed. Compared to controls, MDD
      subjects were more often caught during episodes of PC. In both groups, PC
      required more effort to be inhibited and interfered more with ongoing activities
      compared to mind wandering (MW) (ps < 0.0001). This cognitive rigidity was
      mirrored by autonomic inflexibility, as PC was characterized by lower HRV (p <
      0.0001) compared to MW. A worse mood was reported by MDD patients compared to
      controls, independently of their ongoing cognitive process. Controls, however,
      showed the highest mood worsening during PC compared to being on task and MW. HRV
      during rumination correlated with self-reported somatic symptoms on the same day
      and several dispositional traits. MDD subjects showed lower HRV during sleep,
      which correlated with hopelessness rumination. Results show that PC is associated
      with autonomic dysfunctions in both healthy and MDD subjects. Understanding when
      spontaneous thought is adaptive and when it is not may clarify its role in the
      etiology of mood disorders, shedding light on the still unexplained association
      between psychopathology, chronic stress, and risk for health. 

PMID- 25601825
TI  - Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system
      using an enhanced 2-point Dixon attenuation correction method.
AB  - PURPOSE: To evaluate a potential approach for improved attenuation correction
      (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach
      that adds bone information missing on Dixon AC was explored. METHODS: Bone
      information derived from individual T1-weighted MRI data using segmentation tools
      in SPM8, were added to the standard Dixon AC map. Percent relative difference
      between PET reconstructed with Dixon+bone and with Dixon AC maps were compared
      across brain regions of 13 oncology patients. The clinical potential of the
      improved Dixon AC was investigated by comparing relative perfusion (rCBF)
      measured with arterial spin labeling to relative glucose uptake (rPETdxbone)
      measured simultaneously with (18)F-flurodexoyglucose in several regions across
      the brain. RESULTS: A gradual increase in PET signal from center to the edge of
      the brain was observed in PET reconstructed with Dixon+bone. A 5-20% reduction in
      regional PET signals were observed in data corrected with standard Dixon AC maps.
      These regional underestimations of PET were either reduced or removed when
      Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF
      and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to
      rPET correlation were observed, with the highest associations in the caudate and
      cingulate and the lowest in limbic structures. All findings were well matched to
      observations from previous studies conducted with PET data reconstructed with
      computed tomography derived AC maps. CONCLUSION: Adding bone information derived
      from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity
      in hybrid PET-MRI neuroimaging.

PMID- 25601826
TI  - Pharmacotherapy for anxiety and comorbid alcohol use disorders.
AB  - BACKGROUND: Anxiety disorders are a potentially disabling group of disorders that
      frequently co-occur with alcohol use disorders. Comorbid anxiety and alcohol use
      disorders are associated with poorer outcomes, and are difficult to treat with
      standard psychosocial interventions. In addition, improved understanding of the
      biological basis of the conditions has contributed to a growing interest in the
      use of medications for the treatment of people with both diagnoses. OBJECTIVES:
      To assess the effects of pharmacotherapy for treating anxiety in people with
      comorbid alcohol use disorders, specifically: to provide an estimate of the
      overall effects of medication in improving treatment response and reducing
      symptom severity in the treatment of anxiety disorders in people with comorbid
      alcohol use disorders; to determine whether specific medications are more
      effective and tolerable than other medications in the treatment of particular
      anxiety disorders; and to identify which factors (clinical, methodological)
      predict response to pharmacotherapy for anxiety disorders. SEARCH METHODS: Review
      authors searched the specialized registers of The Cochrane Collaboration
      Depression, Anxiety and Neurosis Review Group (CCDANCTR, to January 2014) and the
      Cochrane Drugs and Alcohol Group (CDAG, to March 2013) for eligible trials. These
      registers contain reports of relevant randomized controlled trials (RCT) from:
      the Cochrane Central Register of Controlled Trials (CENTRAL, all years), MEDLINE
      (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). Review authors
      ran complementary searches on EMBASE, PubMed, PsycINFO and the Alcohol and
      Alcohol Problems Science Database (ETOH) (to August 2013). We located unpublished
      trials through the National Institutes of Health (NIH) RePORTER service and the
      World Health Organization (WHO) International Clinical Trials Registry Platform
      (to August 2013). We screened reference lists of retrieved articles for
      additional studies. SELECTION CRITERIA: All true RCTs of pharmacotherapy for
      treating anxiety disorders with comorbid alcohol use disorders. Trials assessing
      drugs administered for the treatment of drinking behaviour, such as naltrexone,
      disulfiram and acomprosate were not eligible for inclusion in this systematic
      review. DATA COLLECTION AND ANALYSIS: A systematic review is a standardised
      evaluation of all research studies that address a particular clinical issue.Two
      review authors independently assessed RCTs for inclusion in the review, collated
      trial data and assessed trial quality. We contacted investigators to obtain
      missing data. We calculated categorical and continuous treatment effect estimates
      and their 95% confidence intervals (CI) for treatment using a random-effects
      model with effect-size variability expressed using Chi(2) and I(2) heterogeneity
      statistics. MAIN RESULTS: We included five placebo-controlled pharmacotherapy
      RCTs (with 290 participants) in the review. Most of the trials provided little
      information on how randomization was performed or on whether both participants
      and study personnel were blinded to the intervention. Two of the three trials
      reporting superiority of medication compared with placebo on anxiety symptom
      outcomes were industry funded. We regarded one trial as being at high risk of
      bias due to selective reporting.Study participants had Diagnostic and Statistical
      Manual (DSM) III- and DSM IV-diagnosed alcohol use disorders and post-traumatic
      stress disorder (two studies), social anxiety disorder (SAD; two studies) or
      generalized anxiety disorder (GAD; one study). Four trials assessed the efficacy
      of the selective serotonin re-uptake inhibitors (SSRIs: sertraline, paroxetine);
      one RCT investigated the efficacy of buspirone, a 5-hydroxytryptamine (5-HT)
      partial agonist. Treatment duration lasted between eight and 24 weeks. Overall,
      70% of participants included in the review were male.There was very low quality
      evidence for an effect of paroxetine on global clinical response to treatment, as
      assessed by the Clinical Global Impressions - Improvement scale (CGI-I). Global
      clinical response was observed in more than twice as many participants with
      paroxetine than with placebo (57.7% with paroxetine versus 25.8% with placebo;
      risk ratio (RR) 2.23, 95% CI 1.13 to 4.41; 2 trials, 57 participants). However,
      there was substantial uncertainty regarding the size of the effect of paroxetine
      due to the small number of studies providing data on clinically diverse patient
      samples. The second primary outcome measure was reduction of anxiety symptom
      severity. Although study investigators reported that buspirone (one trial) was
      superior to placebo in reducing the severity of anxiety symptoms over 12 weeks,
      no evidence of efficacy was observed for paroxetine (mean difference (MD) -14.70,
      95% CI -33.00 to 3.60, 2 trials, 44 participants) and sertraline (one trial).
      Paroxetine appeared to be equally effective in reducing the severity of post
      traumatic stress disorder (PTSD) symptoms as the tricyclic antidepressant
      desipramine in one RCT. The maximal reduction in anxiety disorder symptom
      severity was achieved after six weeks with paroxetine (two RCTs) and 12 weeks
      with buspirone (one RCT), with maintenance of medication efficacy extending to 16
      with paroxetine and 24 weeks with buspirone. There was no evidence of an effect
      for any of the medications tested on abstinence from alcohol use or depression
      symptoms. There was very low quality evidence that paroxetine was well tolerated,
      based on drop-out due to treatment-emergent adverse effects. Nevertheless, levels
      of treatment discontinuation were high, with 43.1% of the participants in the
      studies withdrawing from medication treatment. Certain adverse effects, such as
      sexual problems, were commonly reported after treatment with paroxetine and
      sertraline. AUTHORS' CONCLUSIONS: The evidence-base for the effectiveness of
      medication in treating anxiety disorders and comorbid alcohol use disorders is
      currently inconclusive. There was a small amount of evidence for the efficacy of
      medication, but this was limited and of very low quality. The majority of the
      data for the efficacy and tolerability of medication were for SSRIs; there were
      insufficient data to establish differences in treatment efficacy between
      medication classes or patient subgroups. There was a small amount of very low
      quality evidence that medication was well tolerated. There was no evidence that
      alcohol use was responsive to medication.Large, rigorously conducted RCTs would
      help supplement the small evidence-base for the efficacy and tolerability of
      pharmacotherapy for anxiety and comorbid alcohol use disorders. Further research
      on patient subgroups who may benefit from pharmacological treatment, as well as
      novel pharmacological interventions, is warranted.

PMID- 25601827
TI  - GABAergic alterations in neocortex of patients with pharmacoresistant temporal
      lobe epilepsy can explain the comorbidity of anxiety and depression: the
      potential impact of clinical factors.
AB  - Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high
      prevalence of psychiatric disorders. Temporal neocortex contributes to either
      seizure propagation or generation in TLE, a situation that has been associated
      with alterations of the gamma-amino-butyric acid (GABA) system. On the other
      hand, an impaired neurotransmission mediated by GABA in temporal neocortex has
      also been involved with the pathophysiology of psychiatric disorders. In spite of
      these situations, the role of the necortical GABA system in the comorbidity of
      TLE and mood disorders has not been investigated. The present study was designed
      to identify alterations in the GABA system such as binding to GABAA and GABAB
      receptors and benzodiazepine site, the tissue content of GABA and the expression
      of the mRNA encoding the alpha1-6, beta1-3, and gamma GABAA subunits, in the
      temporal neocortex of surgically treated patients with TLE with and without
      anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety
      and/or depression showed increased expression of the mRNA encoding the gamma2
      subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB
      binding, and lower tissue content of GABA when compared to autopsy controls. Some
      of these changes significantly correlated with seizure frequency and duration of
      epilepsy. The results obtained suggest a dysfunction of the GABAergic
      neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety
      and/or depression that could be also influenced by clinical factors such as
      seizure frequency and duration of illness. 

PMID- 25601828
TI  - Cortical connectivity maps reveal anatomically distinct areas in the parietal
      cortex of the rat.
AB  - A central feature of theories of spatial navigation involves the representation
      of spatial relationships between objects in complex environments. The parietal
      cortex has long been linked to the processing of spatial visual information and
      recent evidence from single unit recording in rodents suggests a role for this
      region in encoding egocentric and world-centered frames. The rat parietal cortex
      can be subdivided into four distinct rostral-caudal and medial-lateral regions,
      which includes a zone previously characterized as secondary visual cortex. At
      present, very little is known regarding the relative connectivity of these
      parietal subdivisions. Thus, we set out to map the connectivity of the entire
      anterior-posterior and medial-lateral span of this region. To do this we used
      anterograde and retrograde tracers in conjunction with open source neuronal
      segmentation and tracer detection tools to generate whole brain connectivity maps
      of parietal inputs and outputs. Our present results show that inputs to the
      parietal cortex varied significantly along the medial-lateral, but not the
      rostral-caudal axis. Specifically, retrosplenial connectivity is greater
      medially, but connectivity with visual cortex, though generally sparse, is more
      significant laterally. Finally, based on connection density, the connectivity
      between parietal cortex and hippocampus is indirect and likely achieved largely
      via dysgranular retrosplenial cortex. Thus, similar to primates, the parietal
      cortex of rats exhibits a difference in connectivity along the medial-lateral
      axis, which may represent functionally distinct areas. 

PMID- 25601829
TI  - Life-long environmental enrichment counteracts spatial learning, reference and
      working memory deficits in middle-aged rats subjected to perinatal asphyxia.
AB  - Continuous environmental stimulation induced by exposure to enriched environment
      (EE) has yielded cognitive benefits in different models of brain injury.
      Perinatal asphyxia results from a lack of oxygen supply to the fetus and is
      associated with long-lasting neurological deficits. However, the effects of EE in
      middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of
      the present study was to assess whether life-long exposure to EE could counteract
      the cognitive and behavioral alterations in middle-aged asphyctic rats.
      Experimental groups consisted of rats born vaginally (CTL), by cesarean section
      (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were
      assigned to standard (SE) or enriched environment (EE) for 18 months. During the
      last month of housing, animals were submitted to a behavioral test battery
      including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris
      water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE,
      exhibited an impaired performance in the spatial reference and working memory
      versions of the MWM. EE was able to counteract these cognitive impairments.
      Moreover, EE improved the spatial learning performance of middle-aged CTL and C+
      rats. On the other hand, all groups reared in SE did not differ in locomotor
      activity and anxiety levels, while EE reduced locomotion and anxiety, regardless
      of birth condition. Recognition memory was altered neither by birth condition nor
      by housing environment. These results support the importance of environmental
      stimulation across the lifespan to prevent cognitive deficits induced by
      perinatal asphyxia. 

PMID- 25601830
TI  - Neural sensitivity to social reward and punishment anticipation in social anxiety
      disorder.
AB  - An imbalance in the neural motivational system may underlie Social Anxiety
      Disorder (SAD). This study examines social reward and punishment anticipation in
      SAD, predicting a valence-specific effect: increased striatal activity for
      punishment avoidance compared to obtaining a reward. Individuals with SAD (n =
      20) and age, gender, and education case-matched controls (n = 20) participated in
      a functional magnetic resonance imaging (fMRI) study. During fMRI scanning,
      participants performed a Social Incentive Delay (SID) task to measure the
      anticipation of social reward and punishment. The left putamen (part of the
      striatum) showed a valence-specific interaction with group after correcting for
      medication use and comorbidity. The control group showed a relatively stronger
      activation for reward vs. punishment trials, compared to the social anxiety
      group. However, post-hoc pairwise comparisons were not significant, indicating
      that the effect is driven by a relative difference. A connectivity analysis
      (Psychophysiological interaction) further revealed a general salience effect: SAD
      patients showed decreased putamen-ACC connectivity compared to controls for both
      reward and punishment trials. Together these results suggest that the usual
      motivational preference for social reward is absent in SAD. In addition, cortical
      control processes during social incentive anticipation may be disrupted in SAD.
      These results provide initial evidence for altered striatal involvement in both
      valence-specific and valence-nonspecific processing of social incentives, and
      stress the relevance of taking motivational processes into account when studying
      social anxiety. 

PMID- 25601831
TI  - Effectiveness of an impairment-based individualized rehabilitation program using
      an iPad-based software platform.
AB  - The delivery of tablet-based rehabilitation for individuals with post-stroke
      aphasia is relatively new, therefore, this study examined the effectiveness of an
      iPad-based therapy to demonstrate improvement in specific therapy tasks and how
      the tasks affect overall language and cognitive skills. Fifty-one individuals
      with aphasia due to a stroke or traumatic brain injury (TBI) were recruited to
      use an iPad-based software platform, Constant Therapy, for a 10 week therapy
      program. Participants were split into an experimental (N = 42) and control (N =
      9) group. Both experimental and control participants received a 1 h clinic
      session with a clinician once a week, the experimental participants additionally
      practiced the therapy at home. Participants did not differ in the duration of the
      therapy and both groups of participants showed improvement over time in the tasks
      used for the therapy. However, experimental participants used the application
      more often and showed greater changes in accuracy and latency on the tasks than
      the control participants; experimental participants' severity level at baseline
      as measured by standardized tests of language and cognitive skills were a factor
      in improvement on the tasks. Subgroups of task co-improvement appear to occur
      between different language tasks, between different cognitive tasks, and across
      both domains. Finally, experimental participants showed more significant and
      positive changes due to therapy in their standardized tests than control
      participants. These results provide preliminary evidence for the usefulness of a
      tablet-based platform to deliver tailored language and cognitive therapy to
      individuals with aphasia. 

PMID- 25601832
TI  - Beta oscillations, timing, and stuttering.

PMID- 25601834
TI  - Does our brain use the same policy for interacting with people and manipulating
      different objects?

PMID- 25601833
TI  - Robot-assisted training of the kinesthetic sense: enhancing proprioception after
      stroke.
AB  - Proprioception has a crucial role in promoting or hindering motor learning. In
      particular, an intact position sense strongly correlates with the chances of
      recovery after stroke. A great majority of neurological patients present both
      motor dysfunctions and impairments in kinesthesia, but traditional robot and
      virtual reality training techniques focus either in recovering motor functions or
      in assessing proprioceptive deficits. An open challenge is to implement effective
      and reliable tests and training protocols for proprioception that go beyond the
      mere position sense evaluation and exploit the intrinsic bidirectionality of the
      kinesthetic sense, which refers to both sense of position and sense of movement.
      Modulated haptic interaction has a leading role in promoting sensorimotor
      integration, and it is a natural way to enhance volitional effort. Therefore, we
      designed a preliminary clinical study to test a new proprioception-based motor
      training technique for augmenting kinesthetic awareness via haptic feedback. The
      feedback was provided by a robotic manipulandum and the test involved seven
      chronic hemiparetic subjects over 3 weeks. The protocol included evaluation
      sessions that consisted of a psychometric estimate of the subject's kinesthetic
      sensation, and training sessions, in which the subject executed planar reaching
      movements in the absence of vision and under a minimally assistive haptic
      guidance made by sequences of graded force pulses. The bidirectional haptic
      interaction between the subject and the robot was optimally adapted to each
      participant in order to achieve a uniform task difficulty over the workspace. All
      the subjects consistently improved in the perceptual scores as a consequence of
      training. Moreover, they could minimize the level of haptic guidance in time.
      Results suggest that the proposed method is effective in enhancing kinesthetic
      acuity, but the level of impairment may affect the ability of subjects to retain
      their improvement in time. 

PMID- 25601835
TI  - Long-term moderate alcohol consumption does not exacerbate age-related cognitive
      decline in healthy, community-dwelling older adults.
AB  - Recent census data has found that roughly 40% of adults 65 years and older not
      only consume alcohol but also drink more of it than previous generations. Older
      drinkers are more vulnerable than younger counterparts to the psychoactive
      effects of alcohol due to natural biological changes that occur with aging. This
      study was specifically designed to measure the effect of long-term moderate
      alcohol consumption on cognitive health in older adult drinkers. An extensive
      battery of validated tests commonly used in aging and substance use literature
      was used to measure performance in specific cognitive domains, including working
      memory and attention. An age (young, old) (*) alcohol consumption (light,
      moderate) factorial study design was used to evaluate the main effects of age and
      alcohol consumption on cognitive performance. The focus of the study was then
      limited to light and moderate older drinkers, and whether or not long-term
      moderate alcohol consumption exacerbated age-related cognitive decline. No
      evidence was found to support the idea that long-term moderate alcohol
      consumption in older adults exacerbates age-related cognitive decline. Findings
      were specific to healthy community dwelling social drinkers in older age and they
      should not be generalized to individuals with other consumption patterns, like
      heavy drinkers, binge drinkers or ex-drinkers. 

PMID- 25601837
TI  - Frontier impact of microRNAs in skeletal muscle research: a future perspective.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that can regulate the expression of mRNAs
      and proteins by degrading mRNA molecules or by inhibiting their translation. It
      has been predicted that miRNAs regulate approximately 60% of protein-coding genes
      that could be involved in a wide range of biological processes. Research over the
      last 5 years suggests that miRNAs play important roles in skeletal muscle
      function and several miRNAs have been identified as modulators of myogenesis,
      muscle mass, and nutrient metabolism in physiological and pathological states. In
      addition, some miRNAs can be incorporated into intracellular vesicles, released
      into the circulation, transported to other cells, and possibly function in other
      organs in an endocrine manner. This phenomenon might explain the interactions
      between skeletal muscles and other organs. Thus, far, several muscle-secreted
      miRNAs have been identified and their involvement in muscle biology has been
      debated. Based on the recent understanding, this perspective article describes
      the potential valuable role of miRNAs in skeletal muscle function, delineates its
      limitations, and outlines its future perspectives. 

PMID- 25601836
TI  - Encapsulating peritoneal sclerosis-a rare but devastating peritoneal disease.
AB  - Encapsulating peritoneal sclerosis (EPS) is a devastating but, fortunately, rare
      complication of long-term peritoneal dialysis. The disease is associated with
      extensive thickening and fibrosis of the peritoneum resulting in the formation of
      a fibrous cocoon encapsulating the bowel leading to intestinal obstruction. The
      incidence of EPS ranges between 0.7 and 3.3% and increases with duration of
      peritoneal dialysis therapy. Dialysis fluid is hyperosmotic, hyperglycemic, and
      acidic causing chronic injury and inflammation in the peritoneum with loss of
      mesothelium and extensive tissue fibrosis. The pathogenesis of EPS, however,
      still remains uncertain, although a widely accepted hypothesis is the "two-hit
      theory," where, the first hit is chronic peritoneal membrane injury from long
      standing peritoneal dialysis followed by a second hit such as an episode of
      peritonitis, genetic predisposition and/or acute cessation of peritoneal
      dialysis, leading to EPS. Recently, EPS has been reported in patients shortly
      after transplantation suggesting that this procedure may also act as a possible
      second insult. The process of epithelial-mesenchymal transition of mesothelial
      cells is proposed to play a central role in the development of peritoneal
      sclerosis, a common characteristic of patients on dialysis, however, its
      importance in EPS is less clear. There is no established treatment for EPS
      although evidence from small case studies suggests that corticosteroids and
      tamoxifen may be beneficial. Nutritional support is essential and surgical
      intervention (peritonectomy and enterolysis) is recommended in later stages to
      relieve bowel obstruction. 

PMID- 25601838
TI  - Platelet hemostasis in patients with metabolic syndrome and type 2 diabetes
      mellitus: cGMP- and NO-dependent mechanisms in the insulin-mediated platelet
      aggregation.
AB  - Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have
      high risk of microcirculation complications and microangiopathies. An increase in
      thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation,
      and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM
      comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation,
      oxidative stress, and inflammation. This review discusses the role of nitric
      oxide (NO) in the regulation of platelet adhesion and aggregation processes. NO
      is synthesized both in endotheliocytes, smooth muscle cells, macrophages, and
      platelets. Modification of platelet NO-synthase (NOS) activity in MetS patients
      can play a central role in the manifestation of platelet hyperactivation.
      Metabolic changes, accompanying T2DM, can lead to an abnormal NOS expression and
      activity in platelets. Hyperhomocysteinemia, often accompanying T2DM, is a risk
      factor for cardiovascular accidents. Homocysteine can reduce NO production by
      platelets. This review provides data on the insulin effects in platelets.
      Decrease in a number and sensitivity of the insulin receptors on platelets in
      T2DM can cause platelet hyperactivation. Various intracellular mechanisms of anti
      aggregating insulin effects are discussed. Anti-aggregating effects of insulin
      are mediated by a NO-induced elevation of cGMP and upregulation of cAMP- and cGMP
      dependent pathways. The review presents data suggesting an ability of platelets
      to synthesize humoral factors stimulating thrombogenesis and inflammation.
      Proinflammatory cytokines are considered as markers of T2DM and cardiovascular
      complications and are involved in the development of dyslipidemia and insulin
      resistance. The article provides an evaluation of NO-mediated signaling pathway
      in the effects of cytokines on platelet aggregation. The effects of the
      proinflammatory cytokines on functional activity of platelets are demonstrated. 

PMID- 25601839
TI  - Generation of a conditional knockout allele for the NFAT5 gene in mice.
AB  - The osmosensitive transcription factor nuclear factor of activated T-cells 5
      (NFAT5), also known as tonicity enhancer element binding protein (TonEBP) plays a
      crucial role in protection of renal medullary cells against hyperosmotic stress,
      urinary concentration, the adaptive immune response, and other physiological
      systems. Since it is also important for development, conventional homozygous-null
      mutations result in perinatal death, which hinders the analysis of NFAT5 function
      in specific tissues in vivo. Here we describe the generation of mice with a
      conditional-null allele, in which loxP sites are inserted around exon 4. Mice
      harboring the floxed allele (NFAT5(flx) ) were mated to a strain expressing a
      tamoxifen-inducible derivative of the Cre-recombinase (Cre (+)) under the control
      of the ubiqitinC promoter. The resultant homozygous conditional knockout mice
      (Cre (+) NFAT5 (flx/flx) ) are viable, fertile, and show normal expression of
      NFAT5 and NFAT5 target genes, indicating that the conditional alleles retain
      their wild-type function. Induction of Cre-mediated recombination by
      administration of tamoxifen in 8-week-old mice resulted in a decrease in NFAT5
      expression of about 70-90% in all tested tissues (renal cortex, renal outer
      medulla, renal inner medulla, heart, lung, spleen, skeletal muscle). Accordingly,
      the expression of the NFAT5 target genes aldose reductase and heat shock protein
      70 in the renal medulla was also significantly decreased. Mice harboring this
      conditional knockout allele should be useful in future studies for gaining a
      better understanding of tissue and cell-type specific functions of NFAT5 in adult
      animals under physiological and pathophysiological conditions. 

PMID- 25601841
TI  - Mitochondrial efficiency and insulin resistance.
AB  - Insulin resistance, "a relative impairment in the ability of insulin to exert its
      effects on glucose, protein and lipid metabolism in target tissues," has many
      detrimental effects on metabolism and is strongly correlated to deposition of
      lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted
      to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial
      dysfunction in the onset of skeletal muscle insulin resistance has been proposed
      and many studies have dealt with possible alteration in mitochondrial function in
      obesity and diabetes, both in humans and animal models. Data reporting evidence
      of mitochondrial dysfunction in type two diabetes mellitus are numerous, even
      though the issue that this reduced mitochondrial function is causal in the
      development of the disease is not yet solved, also because a variety of
      parameters have been used in the studies carried out on this subject. By
      assessing the alterations in mitochondrial efficiency as well as the impact of
      this parameter on metabolic homeostasis of skeletal muscle cells, we have
      obtained results that allow us to suggest that an increase in mitochondrial
      efficiency precedes and therefore can contribute to the development of high-fat
      induced insulin resistance in skeletal muscle. 

PMID- 25601840
TI  - MSX2 in ameloblast cell fate and activity.
AB  - While many effectors have been identified in enamel matrix and cells via genetic
      studies, physiological networks underlying their expression levels and thus the
      natural spectrum of enamel thickness and degree of mineralization are now just
      emerging. Several transcription factors are candidates for enamel gene expression
      regulation and thus the control of enamel quality. Some of these factors, such as
      MSX2, are mainly confined to the dental epithelium. MSX2 homeoprotein controls
      several stages of the ameloblast life cycle. This chapter introduces MSX2 and its
      target genes in the ameloblast and provides an overview of knowledge regarding
      its effects in vivo in transgenic mouse models. Currently available in vitro data
      on the role of MSX2 as a transcription factor and its links to other players in
      ameloblast gene regulation are considered. MSX2 modulations are relevant to the
      interplay between developmental, hormonal and environmental pathways and in vivo
      investigations, notably in the rodent incisor, have provided insight into dental
      physiology. Indeed, in vivo models are particularly promising for investigating
      enamel formation and MSX2 function in ameloblast cell fate. MSX2 may be central
      to the temporal-spatial restriction of enamel protein production by the dental
      epithelium and thus regulation of enamel quality (thickness and mineralization
      level) under physiological and pathological conditions. Studies on MSX2 show that
      amelogenesis is not an isolated process but is part of the more general
      physiology of coordinated dental-bone complex growth. 

PMID- 25601844
TI  - The D-linking effect on extraction from islands and non-islands.
AB  - "D-linked" wh-phrases such as which car are known to increase the acceptability
      of sentences with island violations. One influential account of this attributes
      the effect to working memory: the D-linked filler is easier to retrieve at the
      site of the gap and this leads to the amelioration in acceptability. Such an
      account predicts that this effect should occur in general with non-trivial wh
      dependencies, not just in island environments. An experiment is presented here to
      test this prediction. Wh-questions with both D-linked and bare wh-phrases and
      with both island and non-island embedded clauses are presented to participants,
      who rate their acceptability on a 7-point scale. Results show that D-linking
      significantly increases acceptability in both island and non-island environments,
      in accord with analyses that attribute the effect to working memory. In addition,
      the increase in acceptability is uniform in both types of environments,
      suggesting that the island effect itself may not be attributable to working
      memory. 

PMID- 25601843
TI  - The modulatory role of second language proficiency on performance monitoring:
      evidence from a saccadic countermanding task in high and low proficient
      bilinguals.
AB  - We compared Hindi-English bilinguals differing in their L2 proficiency on a
      saccadic countermanding task which taps inhibitory control as well as monitoring.
      We particularly explored whether response inhibition and performance monitoring
      within the oculomotor domain are affected by language proficiency in bilinguals.
      There were two different oculomotor redirect tasks: Visually Guided Redirect
      (VGR) task (Experiment1) and Memory Guided Redirect (MGR) task (Experiment 2). In
      the redirect task, typically a target is presented and the subject is required to
      make a saccade (no-step trials), unless a new target appears on a different
      location after some delay from the first target onset (step trials). On such
      trials participants are required to inhibit and cancel the saccade to the first
      target and programme a saccade to the new target. Using trial switch reaction
      time (TSRT), the time taken to inhibit the initiated saccade to the first target
      as a measure of response inhibition and post-step slowing as a measure of
      performance monitoring. The results showed the high proficient bilinguals
      displayed more post-step slowing on the no-step trials as compared to the low
      proficient bilinguals for both VGR and MGR versions of the task. Secondly, both
      the high and low proficient bilinguals exhibited comparable TSRT in both VGR and
      MGR task, showing no modulatory effects of language proficiency on the response
      inhibition. These results suggest that language proficiency may have an effect on
      performance monitoring, but not the inhibitory control per se. Thus, we infer
      that higher proficiency may lead to superior cognitive flexibility and an ability
      to adjust behavior that facilitates the attainment of the cognitive goal. These
      findings are in consonance with other current studies that suggest a top-down
      effect of bilingualism on action control systems. 

PMID- 25601842
TI  - Physical Activity in Schizophrenia is Higher in the First Episode than in
      Subsequent Ones.
AB  - Schizophrenia is frequently associated with abnormal motor behavior, particularly
      hypokinesia. The course of the illness tends to deteriorate in the first years.
      We aimed to assess gross motor activity in patients with a first episode (n = 33)
      and multiple episodes (n = 115) of schizophrenia spectrum disorders using wrist
      actigraphy. First episode patients were younger, had higher motor activity and
      reduced negative symptom severity. Covarying for age, chlorpromazine equivalents,
      and negative symptoms, first episode patients still had higher motor activity.
      This was also true after excluding patients with schizophreniform disorder from
      the analyses. In first episode patients, but not in patients with multiple
      episodes, motor activity was correlated with antipsychotic dosage. In conclusion,
      after controlling for variables related to disorder chronicity, patients with
      first episodes were still more active than patients with multiple episodes. Thus,
      reduced motor activity is a marker of deterioration in the course of
      schizophrenia spectrum disorders. 

PMID- 25601845
TI  - Does listening to action-related sentences modulate the activity of the motor
      system? Replication of a combined TMS and behavioral study.
AB  - The neurophysiological and behavioral correlates of action-related language
      processing have been debated for long time. A precursor in this field was the
      study by Buccino et al. (2005) combining transcranial magnetic stimulation (TMS)
      and behavioral measures (reaction times, RTs) to study the effect of listening to
      hand- and foot-related sentences. In the TMS experiment, the authors showed a
      decrease of motor evoked potentials (MEPs) recorded from hand muscles when
      processing hand-related verbs as compared to foot-related verbs. Similarly, MEPs
      recorded from leg muscles decreased when participants processed foot-related as
      compared to hand-related verbs. In the behavioral experiment, using the same
      stimuli and a semantic decision task the authors found slower RTs when the
      participants used the body effector (hand or foot) involved in the actual
      execution of the action expressed by the presented verb to give their motor
      responses. These findings were interpreted as an interference effect due to a
      simultaneous involvement of the motor system in both a language and a motor task.
      Our replication aimed to enlarge the sample size and replicate the findings with
      higher statistical power. The TMS experiment showed a significant modulation of
      hand MEPs, but in the sense of a motor facilitation when processing hand-related
      verbs. On the contrary, the behavioral experiment did not show significant
      results. The results are discussed within the general debate on the time-course
      of the modulation of motor cortex during implicit and explicit language
      processing and in relation to the studies on action observation/understanding. 

PMID- 25601846
TI  - Warsaw set of emotional facial expression pictures: a validation study of facial
      display photographs.
AB  - Emotional facial expressions play a critical role in theories of emotion and
      figure prominently in research on almost every aspect of emotion. This article
      provides a background for a new database of basic emotional expressions. The goal
      in creating this set was to provide high quality photographs of genuine facial
      expressions. Thus, after proper training, participants were inclined to express
      "felt" emotions. The novel approach taken in this study was also used to
      establish whether a given expression was perceived as intended by untrained
      judges. The judgment task for perceivers was designed to be sensitive to subtle
      changes in meaning caused by the way an emotional display was evoked and
      expressed. Consequently, this allowed us to measure the purity and intensity of
      emotional displays, which are parameters that validation methods used by other
      researchers do not capture. The final set is comprised of those pictures that
      received the highest recognition marks (e.g., accuracy with intended display)
      from independent judges, totaling 210 high quality photographs of 30 individuals.
      Descriptions of the accuracy, intensity, and purity of displayed emotion as well
      as FACS AU's codes are provided for each picture. Given the unique methodology
      applied to gathering and validating this set of pictures, it may be a useful tool
      for research using face stimuli. The Warsaw Set of Emotional Facial Expression
      Pictures (WSEFEP) is freely accessible to the scientific community for non
      commercial use by request at http://www.emotional-face.org. 

PMID- 25601847
TI  - Toward psychiatry as a 'human' science of mind. The case of depressive disorders
      in DSM-5.
AB  - The aim of this paper is to argue that a strictly reductionist approach to
      psychiatry represents a theoretical and clinical obstacle to a fruitful synthesis
      between neurobiological and sociocultural aspects of the sciences of mind. We
      examine the theoretical and practical motivations underlying this approach, by
      analyzing the case of depressive disorders, as defined in the fifth edition of
      the Diagnostic and Statistical Manual of Mental Disorders (DSM), and the related
      removal of the "bereavement exclusion clause." We first explore the claim that
      DSM is atheoretical, observing that, far from being atheoretical, DSM adopts an
      implicit, biologically inspired view of the mind; we show that such a view leads
      to a sort of circularity in the definition of depressive disorders, in which
      psychopharmacology seems to play a key role. We then turn to further problems
      deriving from this position, analyzing the issue of placebo effects in the
      treatment of depressive disorders and the philosophical question of normative
      preconditions for psychopathological diagnosis. Finally, we address the issue of
      subjectivity, which, together with the related aspect of the subject's relational
      context, appears to be crucial to any scientific theorizing about mental
      disorders, despite DSM's attempt to exclude it. Our defense of a non-reductionist
      view of mental disorders, however, does not imply that we endorse any sort of
      metaphysical dualism, or anti-diagnostic or anti-psychiatric positions. On the
      contrary, we argue that the adoption of a reductionist position actually
      undermines the theoretical and clinical accuracy in explaining depressive
      disorders. 

PMID- 25601848
TI  - Children do not exhibit ambiguity aversion despite intact familiarity bias.
AB  - The phenomenon of ambiguity aversion, in which risky gambles with known
      probabilities are preferred over ambiguous gambles with unknown probabilities,
      has been thoroughly documented in adults but never measured in children. Here, we
      use two distinct tasks to investigate ambiguity preferences of children (8- to 9
      year-olds) and a comparison group of adults (19- to 27-year-olds). Across three
      separate measures, we found evidence for significant ambiguity aversion in adults
      but not in children and for greater ambiguity aversion in adults compared to
      children. As ambiguity aversion in adults has been theorized to result from a
      preference to bet on the known and avoid the unfamiliar, we separately measured
      familiarity bias and found that children, like adults, are biased towards the
      familiar. Our findings indicate that ambiguity aversion emerges across the course
      of development between childhood and adolescence, while a familiarity bias is
      already present in childhood. 

PMID- 25601849
TI  - metaSEM: an R package for meta-analysis using structural equation modeling.
AB  - The metaSEM package provides functions to conduct univariate, multivariate, and
      three-level meta-analyses using a structural equation modeling (SEM) approach via
      the OpenMx package in the R statistical platform. It also implements the two
      stage SEM approach to conducting fixed- and random-effects meta-analytic SEM on
      correlation or covariance matrices. This paper briefly outlines the theories and
      their implementations. It provides a summary on how meta-analyses can be
      formulated as structural equation models. The paper closes with a conclusion on
      several relevant topics to this SEM-based meta-analysis. Several examples are
      used to illustrate the procedures in the supplementary material. 

PMID- 25601850
TI  - A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by
      interfering with sensory hair cell and supporting cell cilia length regulation.
AB  - Hearing loss is the most common sensory deficit in humans. We show that a point
      mutation in DCDC2 (DCDC2a), a member of doublecortin domain-containing protein
      superfamily, causes non-syndromic recessive deafness DFNB66 in a Tunisian family.
      Using immunofluorescence on rat inner ear neuroepithelia, DCDC2a was found to
      localize to the kinocilia of sensory hair cells and the primary cilia of
      nonsensory supporting cells. DCDC2a fluorescence is distributed along the length
      of the kinocilium with increased density toward the tip. DCDC2a-GFP
      overexpression in non-polarized COS7 cells induces the formation of long
      microtubule-based cytosolic cables suggesting a role in microtubule formation and
      stabilization. Deafness mutant DCDC2a expression in hair cells and supporting
      cells causes cilium structural defects, such as cilium branching, and up to a 3
      fold increase in length ratios. In zebrafish, the ortholog dcdc2b was found to be
      essential for hair cell development, survival and function. Our results reveal
      DCDC2a to be a deafness gene and a player in hair cell kinocilia and supporting
      cell primary cilia length regulation likely via its role in microtubule formation
      and stabilization. 

PMID- 25601851
TI  - An ER-directed gelsolin nanobody targets the first step in amyloid formation in a
      gelsolin amyloidosis mouse model.
AB  - Hereditary gelsolin amyloidosis is an autosomal dominantly inherited amyloid
      disorder. A point mutation in the GSN gene (G654A being the most common one)
      results in disturbed calcium binding by the second gelsolin domain (G2). As a
      result, the folding of G2 is hampered, rendering the mutant plasma gelsolin
      susceptible to a proteolytic cascade. Consecutive cleavage by furin and MT1-MMP
      like proteases generates 8 and 5 kDa amyloidogenic peptides that cause
      neurological, ophthalmological and dermatological findings. To this day, no
      specific treatment is available to counter the pathogenesis. Using GSN nanobody
      11 as a molecular chaperone, we aimed to protect mutant plasma gelsolin from
      furin proteolysis in the trans-Golgi network. We report a transgenic, GSN
      nanobody 11 secreting mouse that was used for crossbreeding with gelsolin
      amyloidosis mice. Insertion of the therapeutic nanobody gene into the gelsolin
      amyloidosis mouse genome resulted in improved muscle contractility. X-ray crystal
      structure determination of the gelsolin G2:Nb11 complex revealed that Nb11 does
      not directly block the furin cleavage site. We conclude that nanobodies can be
      used to shield substrates from aberrant proteolysis and this approach might
      establish a novel therapeutic strategy in amyloid diseases.

PMID- 25601853
TI  - Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost
      for Multiple Brain Metastases From Lung Adenocarcinoma: Early Response and
      Dosimetric Evaluation.
AB  - In this study, the volume response and treatment outcome after hippocampus
      sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost
      (SIB) using tomotherapy were evaluated. Patients with primary lung adenocarcinoma
      and multiple brain metastases who had a Karnofsky performance status >= 70 and
      exhibited well-controlled extracranial disease were treated. The prescribed dose
      was administered in 10 to 14 fractions as 25 to 28 Gy to whole-brain parenchyma,
      as 40 to 48 Gy to the gross metastatic lesion, and as 30 to 42 Gy to a 5-mm
      margin to the metastatic lesion. Double-dose gadolinium contrast-enhanced
      magnetic resonance imaging at 1-mm slice thickness was performed before treatment
      and at 1, 4, and 7 months post-treatment. The tumor volume reduction ratio was
      calculated for each follow-up. Between July 2011 and September 2012, 11 patients
      with 70 lesions were included in this analysis. The median number of lesions per
      patient was 4 (range, 2-15). The median initial tumor volume was 0.235 cm(3)
      (range, 0.020-10.140 cm(3)). The treatment plans were evaluated regarding
      conformation number (CN), target coverage (TC), and homogeneity index (HI). The
      median follow-up duration was 14 months (range, 3-25 months) and the 1-year
      intracranial control rate was 67%. The tumor volume reduction was most prominent
      during the first month with a median reduction rate of 0.717 (range, -0.190 to
      1.000). Complete remission was seen in 22 (33%) lesions, and 45 (64%) lesions
      showed more than 65% reduction in tumor volume. The CN, TC, and HI values were
      comparable to that of previous studies, and the mean hippocampal dose was 13.65
      Gy. No treatment breaks or >= G3 acute toxicities were observed during or after
      treatment. The HS-WBRT with SIB in patients with multiple brain metastases was
      effective and feasible for volume reduction and showed excellent intracranial
      control.

PMID- 25601852
TI  - Constructing Carbon Fiber Motion-Detection Loops for Simultaneous EEG-fMRI.
AB  - One of the most significant impediments to high-quality EEG recorded in an MRI
      scanner is subject motion. Availability of motion artifact sensors can
      substantially improve the quality of the recorded EEG. In the study of epilepsy,
      it can also dramatically increase the confidence that one has in discriminating
      true epileptiform activity from artifact. This is due both to the reduction in
      artifact and the ability to visually inspect the motion sensor signals when
      reading the EEG, revealing whether or not head motion is present. We have
      previously described the use of carbon fiber loops for detecting and correcting
      artifact in EEG acquired simultaneously with MRI. The loops, attached to the
      subject's head, are electrically insulated from the scalp. They provide a simple
      and direct measure of specific artifact that is contaminating the EEG, including
      both subject motion and residual artifact arising from magnetic field gradients
      applied during MRI. Our previous implementation was used together with a custom
      built EEG-fMRI system that differs substantially from current commercially
      available EEG-fMRI systems. The present technical note extends this work,
      describing in more detail how to construct the carbon fiber motion-detection
      loops, and how to interface them with a commercially available simultaneous EEG
      fMRI system. We hope that the information provided may help those wishing to
      utilize a motion-detection/correction solution to improve the quality of EEG
      recorded within an MRI scanner. 

PMID- 25601854
TI  - Hypoxic Microenvironment Induces EMT and Upgrades Stem-Like Properties of Gastric
      Cancer Cells.
AB  - Hypoxia microenvironment, as a major feature of solid tumors, increases tumors
      progression and metastasis. To research whether hypoxia influences the epithelial
      mesenchymal transition (EMT) and cancer stem cells (CSCs) of gastric cancer cells
      and their cell biological behaviors. Human gastric cancer cell lines BGC823 and
      SGC7901 were cultivated in different oxygen tensions for proliferation, colony
      formation, soft agar formation, migration, and invasion analyses. Markers of EMT
      (E-cadherin, N-cadherin, Vimentin, and Snail) and markers of CSCs (Sox2, Oct4,
      and Bmi1) were investigated by real-time polymerase chain reaction, Western
      blotting, and immunofluorescent analysis. Cultivated at hypoxic condition, BGC823
      and SGC7901 cells morphology began to change significantly. The cells pretreated
      under hypoxia grew faster than those cells always cultivated in normoxia.
      Meanwhile, hypoxia pretreatment dramatically promoted cell proliferation,
      migration and invasion, and increased capability of colony and soft agar colony
      formation. Furthermore, under hypoxia, E-cadherin decreased and N-cadherin,
      Vimentin, Snail, Sox2, Oct4, and Bmi1 increased both on the level of messenger
      RNA and protein. We drew a conclusion that the hypoxic microenvironment induced
      EMT, upgraded stem-like properties of gastric cancer cells, promoted invasion and
      metastasis, and behaved more malignantly.

PMID- 25601855
TI  - Differential Effects of Insulin-Like Growth Factor Binding Protein-6 (IGFBP-6) on
      Migration of Two Ovarian Cancer Cell Lines.
AB  - INTRODUCTION: IGFBP-6 inhibits angiogenesis as well as proliferation and survival
      of rhabdomyosarcoma cells. However, it promotes migration of these cells in an
      IGF-independent manner. The IGF system is implicated in ovarian cancer, so we
      studied the effects of IGFBP-6 in ovarian cancer cells. METHODS: The effects of
      wild type (wt) and a non-IGF-binding mutant (m) of IGFBP-6 on migration of HEY
      and SKOV3 ovarian cancer cells, which, respectively, represent aggressive and
      transitional cancers, were studied. ERK and JNK phosphorylation were measured by
      Western blotting. RESULTS: IGF-II, wt-, and mIGFBP-6 each promoted SKOV3 cell
      migration by 77-98% (p < 0.01). In contrast, IGF-II also increased HEY cell
      migration to 155 +/- 13% of control (p < 0.001), but wt-IGFBP-6 and mIGFBP-6
      decreased migration to 62 +/- 5 and 66 +/- 3%, respectively (p < 0.001). In these
      cells, coincubation of IGF-II with wt but not mIGFBP-6 increased migration. MAP
      kinase pathways are involved in IGFBP-6-induced rhabdomyosarcoma cell migration,
      so activation of these pathways was studied in HEY and SKOV3 cells. Wt and mIGFBP
      6 increased ERK phosphorylation by 62-99% in both cell lines (p < 0.05). Wt-IGFBP
      6 also increased JNK phosphorylation by 139-153% in both cell lines (p < 0.05),
      but the effect of mIGFBP-6 was less clear. ERK and JNK inhibitors partially
      inhibited the migratory effects of wt and mIGFBP-6 in SKOV3 cells, whereas the
      ERK inhibitor partially restored wt and mIGFBP-6-induced inhibition of HEY cell
      migration. The JNK inhibitor had a lesser effect on the actions of wtIGFBP-6 and
      no effect on the actions of mIGFBP-6 in HEY cells. CONCLUSION: IGFBP-6 has
      opposing effects on migration of HEY and SKOV3 ovarian cancer cells, but
      activates MAP kinase pathways in both. Delineating the pathways underlying the
      differential effects on migration will increase our understanding of ovarian
      cancer metastasis and shed new light on the IGF-independent effects of IGFBP-6.

PMID- 25601856
TI  - Biogeographic patterns of bacterial microdiversity in Arctic deep-sea sediments
      (HAUSGARTEN, Fram Strait).
AB  - Marine bacteria colonizing deep-sea sediments beneath the Arctic ocean, a rapidly
      changing ecosystem, have been shown to exhibit significant biogeographic patterns
      along transects spanning tens of kilometers and across water depths of several
      thousand meters (Jacob et al., 2013). Jacob et al. (2013) adopted what has become
      a classical view of microbial diversity - based on operational taxonomic units
      clustered at the 97% sequence identity level of the 16S rRNA gene - and observed
      a very large microbial community replacement at the HAUSGARTEN Long Term
      Ecological Research station (Eastern Fram Strait). Here, we revisited these data
      using the oligotyping approach and aimed to obtain new insight into ecological
      and biogeographic patterns associated with bacterial microdiversity in marine
      sediments. We also assessed the level of concordance of these insights with
      previously obtained results. Variation in oligotype dispersal range, relative
      abundance, co-occurrence, and taxonomic identity were related to environmental
      parameters such as water depth, biomass, and sedimentary pigment concentration.
      This study assesses ecological implications of the new microdiversity-based
      technique using a well-characterized dataset of high relevance for global change
      biology. 

PMID- 25601857
TI  - Endogenous cross-talk of fungal metabolites.
AB  - Non-ribosomal peptide (NRP) synthesis in fungi requires a ready supply of
      proteogenic and non-proteogenic amino acids which are subsequently incorporated
      into the nascent NRP via a thiotemplate mechanism catalyzed by NRP synthetases.
      Substrate amino acids can be modified prior to or during incorporation into the
      NRP, or following incorporation into an early stage amino acid-containing
      biosynthetic intermediate. These post-incorporation modifications involve a range
      of additional enzymatic activities including but not exclusively, monooxygenases,
      methyltransferases, epimerases, oxidoreductases, and glutathione S-transferases
      which are essential to effect biosynthesis of the final NRP. Likewise, polyketide
      biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded
      ancillary decorating enzymes. Additionally, a suite of additional primary
      metabolites, for example: coenzyme A (CoA), acetyl CoA, S-adenosylmethionine,
      glutathione (GSH), NADPH, malonyl CoA, and molecular oxygen, amongst others are
      required for NRP and polyketide synthesis (PKS). Clearly these processes must
      involve exquisite orchestration to facilitate the simultaneous biosynthesis of
      different types of NRPs, polyketides, and related metabolites requiring identical
      or similar biosynthetic precursors or co-factors. Moreover, the near identical
      structures of many natural products within a given family (e.g., ergot
      alkaloids), along with localization to similar regions within fungi (e.g.,
      conidia) suggests that cross-talk may exist, in terms of biosynthesis and
      functionality. Finally, we speculate if certain biosynthetic steps involved in
      NRP and PKS play a role in cellular protection or environmental adaptation, and
      wonder if these enzymatic reactions are of equivalent importance to the actual
      biosynthesis of the final metabolite. 

PMID- 25601859
TI  - Campylobacter jejuni acquire new host-derived CRISPR spacers when in association
      with bacteriophages harboring a CRISPR-like Cas4 protein.
AB  - Campylobacter jejuni is a worldwide cause of human diarrhoeal disease. Clustered
      Repetitively Interspaced Palindromic Repeats (CRISPRs) and associated proteins
      allow Bacteria and Archaea to evade bacteriophage and plasmid infection. Type II
      CRISPR systems are found in association with combinations of genes encoding the
      CRISPR-associated Cas1, Cas2, Cas4 or Csn2, and Cas9 proteins. C. jejuni
      possesses a minimal subtype II-C CRISPR system containing cas1, cas2, and cas9
      genes whilst cas4 is notably absent. Cas4 proteins possess 5'-3' exonuclease
      activity to create recombinogenic-ends for spacer acquisition. Here we report a
      conserved Cas4-like protein in Campylobacter bacteriophages that creates a novel
      split arrangement between the bacteriophage and host that represents a new twist
      in the bacteriophage/host co-evolutionary arms race. The continuous association
      of bacteriophage and host in the carrier state life cycle of C. jejuni provided
      an opportunity to study spacer acquisition in this species. Remarkably all the
      spacer sequences observed were of host origin. We hypothesize that Campylobacter
      bacteriophages can use Cas4-like protein to activate spacer acquisition to use
      host DNA as an effective decoy to bacteriophage DNA. Bacteria that acquire self
      spacers and escape phage infection must overcome CRISPR-mediated autoimmunity
      either by loss of the interference functions leaving them susceptible to foreign
      DNA incursion or tolerate changes in gene regulation. 

PMID- 25601858
TI  - Endothelial cell dysfunction in viral hemorrhage and edema.
AB  - The endothelium maintains a vascular barrier by controlling platelet and immune
      cell interactions, capillary tone and interendothelial cell (EC) adherence. Here
      we suggest common elements in play during viral infection of the endothelium that
      alter normal EC functions and contribute to lethal hemorrhagic or edematous
      diseases. In viral reservoir hosts, infection of capillaries and lymphatic
      vessels may direct immunotolerance without disease, but in the absence of these
      cognate interactions they direct the delayed onset of human disease characterized
      by thrombocytopenia and vascular leakage in a severe endothelial dysfunction
      syndrome. Here we present insight into EC controls of hemostasis, immune response
      and capillary permeability that are altered by viral infection of the
      endothelium. 

PMID- 25601860
TI  - The importance of mouse models to define immunovirologic determinants of
      progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a severely debilitating and
      often fatal demyelinating disease of the central nervous system (CNS) in
      immunosuppressed individuals caused by JC polyomavirus (JCV), a ubiquitous human
      pathogen. Demyelination results from lytically infected oligodendrocytes, whose
      clearance is impaired in the setting of depressed JCV-specific T cell-mediated
      CNS surveillance. Although mutations in the viral capsid and genomic
      rearrangements in the viral non-coding region appear to set the stage for PML in
      the immunosuppressed population, mechanisms of demyelination and CNS antiviral
      immunity are poorly understood in large part due to absence of a tractable animal
      model that mimics PML neuropathology in humans. Early studies using mouse
      polyomavirus (MPyV) in T cell-deficient mice demonstrated productive viral
      replication in the CNS and demyelination; however, these findings were confounded
      by spinal cord compression by virus-induced vertebral bone tumors. Here, we
      review current literature regarding animal models of PML, focusing on current
      trends in antiviral T cell immunity in non-lymphoid organs, including the CNS.
      Advances in our understanding of polyomavirus lifecycles, viral and host
      determinants of persistent infection, and T cell-mediated immunity to viral
      infections in the CNS warrant revisiting polyomavirus CNS infection in the mouse
      as a bona fide animal model for JCV-PML. 

PMID- 25601861
TI  - Molecules and Mechanisms Implicated in the Peculiar Antigenic Activation Process
      of Human Vgamma9Vdelta2 T Cells.
AB  - In human beings, as well as in most non-human primates, the major peripheral
      gammadelta T cell subset, which accounts several percent of the whole lymphoid
      cells pool in adults, carries an heterodimeric TCR composed of Vgamma9 and
      Vdelta2 chains. Vgamma9Vdelta2 T cells are specifically and strongly activated by
      small organic pyrophosphate molecules termed phosphoantigens (phosphoAg). These
      low molecular weight compounds are metabolites that are produced by either
      microbes or endogenously, as intermediates of the mammalian mevalonate pathway,
      and can accumulate intracellularly during cell stress like transformation or
      infection. Despite the characterization of numerous natural and synthetic
      phosphoAg, the mechanism(s) underlying the unique and specific antigenic
      activation process induced by these compounds remains poorly understood.
      Activation is both TCR- and cell-to-cell contact-dependent, and results of
      previous studies have also strongly suggested a key contribution of membrane
      associated molecules of primate origin expressed on target cells. The recent
      identification of B7-related butyrophilin (BTN) molecules CD277/BTN3A, and more
      precisely their BTN3A1 isoforms, as mandatory molecules in the phosphoAg-induced
      recognition of target cells by Vgamma9Vdelta2 T cells opens important
      opportunities for research and applications in this field. Here, we review the
      unusual and complex antigenic reactivity of human Vgamma9Vdelta2 T cells. We
      highlight the recent advances in our understanding of this process, and propose a
      model that integrates the type I glycoprotein BTN3A1 and its intracellular B30.2
      domain as a physical intermediate implicated in the detection of dysregulated
      intracellular levels of phosphoAg and the sensing of cell stress by
      Vgamma9Vdelta2T cells. A better understanding of this mechanism will help
      optimize novel immunotherapeutical approaches that utilize the unique functional
      potential of this major gammadelta T cell subset. 

PMID- 25601862
TI  - Systems Biology Strategy Reveals PKCdelta is Key for Sensitizing TRAIL-Resistant
      Human Fibrosarcoma.
AB  - Cancer cells are highly variable and largely resistant to therapeutic
      intervention. Recently, the use of the tumor necrosis factor related apoptosis
      inducing ligand (TRAIL) induced treatment is gaining momentum due to TRAIL's
      ability to specifically target cancers with limited effect on normal cells.
      Nevertheless, several malignant cancer types still remain non-sensitive to TRAIL.
      Previously, we developed a dynamic computational model, based on perturbation
      response differential equations approach, and predicted protein kinase C (PKC) as
      the most effective target, with over 95% capacity to kill human fibrosarcoma
      (HT1080) in TRAIL stimulation (1). Here, to validate the model prediction, which
      has significant implications for cancer treatment, we conducted experiments on
      two TRAIL-resistant cancer cell lines (HT1080 and HT29). Using PKC inhibitor
      bisindolylmaleimide I, we demonstrated that cell viability is significantly
      impaired with over 95% death of both cancer types, in consistency with our
      previous model. Next, we measured caspase-3, Poly (ADP-ribose) polymerase (PARP),
      p38, and JNK activations in HT1080, and confirmed cell death occurs through
      apoptosis with significant increment in caspase-3 and PARP activations. Finally,
      to identify a crucial PKC isoform, from 10 known members, we analyzed each
      isoform mRNA expressions in HT1080 cells and shortlisted the highest 4 for
      further siRNA knock-down (KD) experiments. From these KDs, PKCdelta produced the
      most cancer cell death in conjunction with TRAIL. Overall, our approach combining
      model predictions with experimental validation holds promise for systems biology
      based cancer therapy. 

PMID- 25601864
TI  - Gamma interferon: from antimicrobial activity to immune regulation.

PMID- 25601863
TI  - Regulation of immune responses by the neonatal fc receptor and its therapeutic
      implications.
AB  - As a single receptor, the neonatal Fc receptor (FcRn) is critically involved in
      regulating albumin and IgG serum concentrations by protecting these two ligands
      from degradation. In addition to these essential homeostatic functions, FcRn
      possesses important functions in regulating immune responses that are equally as
      critical and are increasingly coming to attention. During the first stages of
      life, FcRn mediates the passive transfer of IgG across the maternal placenta or
      neonatal intestinal walls of mammals, thereby conferring passive immunity to the
      offspring before and after birth. In fact, FcRn is one of the very few molecules
      that are known to move from luminal to serosal membranes of polarized cells that
      form epithelial barriers of the lung and intestines. Together with FcRn's
      recently explored critical role in eliciting MHC II presentation and MHC class I
      cross-presentation of IgG-complexed antigen, this renders FcRn capable of
      exerting broad and potent functions in regulating immune responses and
      immunosurveillance at mucosal sites. Further, it is now clear that FcRn dependent
      mucosal absorption of therapeutic molecules is a clinically feasible and potent
      novel route of non-invasive drug delivery, and the interaction between FcRn and
      IgG has also been utilized for the acquisition of humoral immunity at mucosal
      sites. In this review, we begin by briefly summarizing the basic knowledge on
      FcRn expression and IgG binding, then describe more recent discoveries pertaining
      to the mechanisms by which FcRn orchestrates IgG related mucosal immune responses
      and immunosurveillance at host-environment interfaces within the adult organism.
      Finally, we outline how the knowledge of actions of FcRn at mucosal boundaries
      can be capitalized for the development and engineering of powerful mucosal
      vaccination strategies and novel routes for the non-invasive delivery of Fc-based
      therapeutics. 

PMID- 25601865
TI  - Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab.
AB  - Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain,
      has been approved for the treatment of active multiple sclerosis, but expose to
      the onset of a rare side effect, progressive multifocal leukoencephalopathy
      (PML). Estimating the individual risk of PML in NTZ-treated patients is a major
      challenge, and therapeutic strategies are mainly guided by the overall PML risk
      assessed by identified risk factors: JC virus (JCV) seropositivity, treatment
      duration (with peak incidence after 24 months), and the previous use of
      immunosuppressive therapies. Given that this stratification does not yet allow a
      precise individual prediction of PML, other predictive markers are needed, and
      several immunological biomarkers have been described. Quantification of anti-JCV
      antibody levels may improve individual predictive value, with higher baseline
      titers indicating increased risk. Other immunological biomarkers such as
      leukocyte cell membrane markers (CD49d, CD11a, and CD62L), detection of
      circulating JCV-specific activated T effector memory cells (TEM) or genetic
      screening have been proposed. In this review, we discuss how recent progress in
      immunology has paved the way for "new combined monitoring", which will include
      immunological screening, in NTZ-treated patients. 

PMID- 25601866
TI  - Prediction of the Pharmacokinetics, Pharmacodynamics, and Efficacy of a
      Monoclonal Antibody, Using a Physiologically Based Pharmacokinetic FcRn Model.
AB  - Although advantages of physiologically based pharmacokinetic models (PBPK) are
      now well established, PBPK models that are linked to pharmacodynamic (PD) models
      to predict pharmacokinetics (PK), PD, and efficacy of monoclonal antibodies
      (mAbs) in humans are uncommon. The aim of this study was to develop a PD model
      that could be linked to a physiologically based mechanistic FcRn model to predict
      PK, PD, and efficacy of efalizumab. The mechanistic FcRn model for mAbs with
      target-mediated drug disposition within the Simcyp population-based simulator was
      used to simulate the pharmacokinetic profiles for three different single doses
      and two multiple doses of efalizumab administered to virtual Caucasian healthy
      volunteers. The elimination of efalizumab was modeled with both a target-mediated
      component (specific) and catabolism in the endosome (non-specific). This model
      accounted for the binding between neonatal Fc receptor (FcRn) and efalizumab
      (protective against elimination) and for changes in CD11a target concentration.
      An integrated response model was then developed to predict the changes in mean
      Psoriasis Area and Severity Index (PASI) scores that were measured in a clinical
      study as an efficacy marker for efalizumab treatment. PASI scores were
      approximated as continuous and following a first-order asymptotic progression
      model. The reported steady state asymptote (Y ss) and baseline score [Y (0)] was
      applied and parameter estimation was used to determine the half-life of
      progression (T p) of psoriasis. Results suggested that simulations using this
      model were able to recover the changes in PASI scores (indicating efficacy)
      observed during clinical studies. Simulations of both single dose and multiple
      doses of efalizumab concentration-time profiles as well as suppression of CD11a
      concentrations recovered clinical data reasonably well. It can be concluded that
      the developed PBPK FcRn model linked to a PD model adequately predicted PK, PD,
      and efficacy of efalizumab. 

PMID- 25601867
TI  - Antigen Presentation by MHC-Dressed Cells.
AB  - Professional antigen-presenting cells (APCs) such as conventional dendritic cells
      (DCs) process protein antigens to MHC-bound peptides and then present the peptide
      MHC complexes to T cells. In addition to this canonical antigen presentation
      pathway, recent studies have revealed that DCs and non-APCs can acquire MHC class
      I (MHCI) and/or MHC class II (MHCII) from neighboring cells through a process of
      cell-cell contact-dependent membrane transfer called trogocytosis. These MHC
      dressed cells subsequently activate or regulate T cells via the preformed antigen
      peptide-MHC complexes without requiring any further processing. In addition to
      trogocytosis, intercellular transfer of MHCI and MHCII can be mediated by
      secretion of membrane vesicles such as exosomes from APCs, generating MHC-dressed
      cells. This review focuses on the physiological role of antigen presentation by
      MHCI- or MHCII-dressed cells, and also discusses differences and similarities
      between trogocytosis and exosome-mediated transfer of MHC. 

PMID- 25601868
TI  - Analysis of specific IgG titers against tick-borne encephalitis in patients with
      primary antibody deficiency under immunoglobulin substitution therapy: impact of
      plasma donor origin.
AB  - Immunoglobulin (Ig) replacement therapy is effective in reducing infections in
      patients with primary antibody deficiency (PAD). Diversity of specific antibodies
      is achieved by pooling plasma from over 1000 donors usually of a given geographic
      region. However, there is no agreement with regard to an optimal vaccination
      schedule for plasma donors. Especially for tick-borne encephalitis (TBE),
      regional vaccination rates differ widely among populations due to the
      epidemiology of the disease. We analyzed specific antibody titers against TBE in
      comparison to total IgG levels in 162 serum samples collected from 110 PAD
      patients substituted with polyvalent intravenous IgG or subcutaneous IgG. Some
      patients received different IgG products over time leading to a total number of
      122 different patient-IgG product combinations. Positive TBE-specific IgG levels
      were detected in 35 cases when measured by standard ELISA and could be confirmed
      by demonstration of neutralizing antibodies in 31 cases. The detection of
      specific antibody levels correlated with the geographic origin of the IgG
      preparations. No titers were detectable in patients substituted with IgG products
      from North-American donors, whereas variable degrees of anti-TBE titers were
      observed in patients receiving products from different European countries. We
      suggest considering the patients' personal risk for TBE when selecting an
      appropriate Ig preparation. These data support regional plasma donation in order
      to address the diverse local infection profile. 

PMID- 25601869
TI  - Metabolic syndrome and the immunological affair with the blood-brain barrier.
AB  - Epidemiological studies reveal an increased incidence of obesity worldwide, which
      is associated with increased prevalence and severity of cognitive disorders. The
      blood-brain barrier (BBB) represents the interface between the peripheral
      circulation and the brain, and plays a fundamental role in the cross-talk between
      these two compartments. The homeostatic function of the BBB is the protection of
      the brain from peripheral insult/inflammation. Alterations in the function of the
      BBB lead to pathologies of the central nervous system. Recently, metabolic
      imbalance has been shown to be an important risk factor associated with the
      decline of BBB integrity and function. This has direct etiological consequences
      on a variety of cerebrovascular and neurodegenerative pathologies with great
      impact to society. Priority areas for future preclinical research include
      strategies to improve clinicians' ability to diagnose, prevent, and manage BBB
      abnormalities. In sharp contrast with epidemiological studies and clinical needs,
      little is known about the mechanisms that link metabolic syndrome to BBB
      functionality and cognitive disorders. Our view is that immune responses caused
      by metabolic stress might play a major role in this conundrum. 

PMID- 25601870
TI  - Novel connections and gaps in ethylene signaling from the ER membrane to the
      nucleus.
AB  - The signaling of the plant hormone ethylene has been studied genetically,
      resulting in the identification of signaling components from membrane receptors
      to nuclear effectors. Among constituents of the hormone signaling pathway,
      functional links involving a putative mitogen-activated protein kinase kinase
      CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) and a membrane transporter-like protein
      ETHYLENE INSENSITIVE2 (EIN2) have been missing for a long time. We now learn that
      EIN2 is cleaved and its C-terminal end moves to the nucleus upon ethylene
      perception at the membrane receptors, and then the C-terminal end of EIN2 in the
      nucleus supports EIN3-dependent ethylene-response gene expression. CTR1 kinase
      activity negatively controls the EIN2 cleavage process through direct
      phosphorylation. Despite the novel connection of CTR1 with EIN2 that explains a
      large portion of the missing links in ethylene signaling, our understanding still
      remains far from its completion. This focused review will summarize recent
      advances in the EIN3-dependent ethylene signaling mechanisms including CTR1-EIN2
      functions with respect to EIN3 regulation and ethylene responses. This will also
      present several emerging issues that need to be addressed for the comprehensive
      understanding of signaling pathways of the invaluable plant hormone ethylene. 

PMID- 25601871
TI  - Image-based phenotyping of plant disease symptoms.
AB  - Plant diseases cause significant reductions in agricultural productivity
      worldwide. Disease symptoms have deleterious effects on the growth and
      development of crop plants, limiting yields and making agricultural products
      unfit for consumption. For many plant-pathogen systems, we lack knowledge of the
      physiological mechanisms that link pathogen infection and the production of
      disease symptoms in the host. A variety of quantitative high-throughput image
      based methods for phenotyping plant growth and development are currently being
      developed. These methods range from detailed analysis of a single plant over time
      to broad assessment of the crop canopy for thousands of plants in a field and
      employ a wide variety of imaging technologies. Application of these methods to
      the study of plant disease offers the ability to study quantitatively how host
      physiology is altered by pathogen infection. These approaches have the potential
      to provide insight into the physiological mechanisms underlying disease symptom
      development. Furthermore, imaging techniques that detect the electromagnetic
      spectrum outside of visible light allow us to quantify disease symptoms that are
      not visible by eye, increasing the range of symptoms we can observe and
      potentially allowing for earlier and more thorough symptom detection. In this
      review, we summarize current progress in plant disease phenotyping and suggest
      future directions that will accelerate the development of resistant crop
      varieties. 

PMID- 25601872
TI  - Positive-negative-selection-mediated gene targeting in rice.
AB  - Gene targeting (GT) refers to the designed modification of genomic sequence(s)
      through homologous recombination (HR). GT is a powerful tool both for the study
      of gene function and for molecular breeding. However, in transformation of higher
      plants, non-homologous end joining (NHEJ) occurs overwhelmingly in somatic cells,
      masking HR-mediated GT. Positive-negative selection (PNS) is an approach for
      finding HR-mediated GT events because it can eliminate NHEJ effectively by
      expression of a negative-selection marker gene. In rice-a major crop worldwide
      reproducible PNS-mediated GT of endogenous genes has now been successfully
      achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment
      as a negative marker, and has succeeded in the directed modification of several
      endogenous rice genes in various ways. In addition to gene knock-outs and knock
      ins, a nucleotide substitution in a target gene was also achieved recently. This
      review presents a summary of the development of the rice PNS system, highlighting
      its advantages. Different types of gene modification and gene editing aimed at
      developing new plant breeding technology based on PNS are discussed. 

PMID- 25601873
TI  - Fires in the Cenozoic: a late flowering of flammable ecosystems.
AB  - Modern flammable ecosystems include tropical and subtropical savannas, steppe
      grasslands, boreal forests, and temperate sclerophyll shrublands. Despite the
      apparent fiery nature of much contemporary vegetation, terrestrial fossil
      evidence would suggest we live in a time of low fire activity relative to the
      deep past. The inertinite content of coal, fossil charcoal, is strikingly low
      from the Eocene to the Pleistocene and no charcoalified mesofossils have been
      reported for the Cenozoic. Marine cores have been analyzed for charcoal in the
      North Pacific, the north and south Atlantic off Africa, and the south China sea.
      These tell a different story with the oldest records indicating low levels of
      fire activity from the Eocene but a surge of fire from the late Miocene (~7 Ma).
      Phylogenetic studies of woody plants adapted to frequent savanna fires show them
      beginning to appear from the Late Miocene with peak origins in the late Pliocene
      in both South American and African lineages. Phylogenetic studies indicate
      ancient origins (60 Ma+) for clades characteristic of flammable sclerophyll
      vegetation from Australia and the Cape region of South Africa. However, as for
      savannas, there was a surge of speciation from the Late Miocene associated with
      the retreat of closed fire-intolerant forests. The wide geographic spread of
      increased fire activity in the last few million years suggests a global cause.
      However, none of the potential global factors (oxygen, rainfall seasonality, CO2,
      novel flammable growth forms) provides an adequate explanation as yet. The global
      patterns and processes of fire and flammable vegetation in the Cenozoic,
      especially since the Late Miocene, deserve much more attention to better
      understand fire in the earth system. 

PMID- 25601874
TI  - Alternative translational initiation of ATP sulfurylase underlying dual
      localization of sulfate assimilation pathways in plastids and cytosol in
      Arabidopsis thaliana.
AB  - Plants assimilate inorganic sulfate into sulfur-containing vital metabolites. ATP
      sulfurylase (ATPS) is the enzyme catalyzing the key entry step of the sulfate
      assimilation pathway in both plastids and cytosol in plants. Arabidopsis thaliana
      has four ATPS genes (ATPS1, -2, -3, and -4) encoding ATPS pre-proteins containing
      N-terminal transit peptide sequences for plastid targeting, however, the genetic
      identity of the cytosolic ATPS has remained unverified. Here we show that
      Arabidopsis ATPS2 dually encodes plastidic and cytosolic ATPS isoforms,
      differentiating their subcellular localizations by initiating translation at
      AUG(Met1) to produce plastid-targeted ATPS2 pre-proteins or at AUG(Met52) or
      AUG(Met58) within the transit peptide to have ATPS2 stay in cytosol.
      Translational initiation of ATPS2 at AUG(Met52) or AUG(Met58) was verified by
      expressing a tandem-fused synthetic gene, ATPS2 (5'UTR-His12) :Renilla
      luciferase:ATPS2 (Ile13-Val77) :firefly luciferase, under a single constitutively
      active CaMV 35S promoter in Arabidopsis protoplasts and examining the activities
      of two different luciferases translated in-frame with split N-terminal portions
      of ATPS2. Introducing missense mutations at AUG(Met52) and AUG(Met58)
      significantly reduced the firefly luciferase activity, while AUG(Met52) was a
      relatively preferred site for the alternative translational initiation. The
      activity of luciferase fusion protein starting at AUG(Met52) or AUG(Met58) was
      not modulated by changes in sulfate conditions. The dual localizations of ATPS2
      in plastids and cytosol were further evidenced by expression of ATPS2-GFP fusion
      proteins in Arabidopsis protoplasts and transgenic lines, while they were also
      under control of tissue-specific ATPS2 promoter activity found predominantly in
      leaf epidermal cells, guard cells, vascular tissues and roots. 

PMID- 25601875
TI  - Ecopiling: a combined phytoremediation and passive biopiling system for
      remediating hydrocarbon impacted soils at field scale.
AB  - Biopiling is an ex situ bioremediation technology that has been extensively used
      for remediating a wide range of petrochemical contaminants in soils. Biopiling
      involves the assembling of contaminated soils into piles and stimulating the
      biodegrading activity of microbial populations by creating near optimum growth
      conditions. Phytoremediation is another very successful bioremediation technique
      and involves the use of plants and their associated microbiomes to degrade,
      sequester or bio-accumulate pollutants from contaminated soil and water. The
      objective of this study was to investigate the effectiveness of a combined
      phytoremediation/biopiling system, termed Ecopiling, to remediate hydrocarbon
      impacted industrial soil. The large scale project was carried out on a sandy
      loam, petroleum impacted soil [1613 mg total petroleum hydrocarbons (TPHs) kg(-1)
      soil]. The contaminated soil was amended with chemical fertilizers, inoculated
      with TPH degrading bacterial consortia and then used to construct passive
      biopiles. Finally, a phyto-cap of perennial rye grass (Lolium perenne) and white
      clover (Trifolium repens) was sown on the soil surface to complete the Ecopile.
      Monitoring of important physico-chemical parameters was carried out at regular
      intervals throughout the trial. Two years after construction the TPH levels in
      the petroleum impacted Ecopiles were below detectable limits in all but one
      subsample (152 mg TPH kg(-1) soil). The Ecopile system is a multi-factorial
      bioremediation process involving bio-stimulation, bio-augmentation and
      phytoremediation. One of the key advantages to this system is the reduced costs
      of the remediation process, as once constructed, there is little additional cost
      in terms of labor and maintenance (although the longer process time may incur
      additional monitoring costs). The other major advantage is that many ecological
      functions are rapidly restored to the site and the process is esthetically
      pleasing. 

PMID- 25601877
TI  - Forced adaptation: plant proteins to fight climate change.

PMID- 25601878
TI  - Hybrid origin of European commercial pigs examined by an in-depth haplotype
      analysis on chromosome 1.
AB  - Although all farm animals have an original source of domestication, a large
      variety of modern breeds exist that are phenotypically highly distinct from the
      ancestral wild population. This phenomenon can be the result of artificial
      selection or gene flow from other sources into the domesticated population. The
      Eurasian wild boar (Sus scrofa) has been domesticated at least twice in two
      geographically distinct regions during the Neolithic revolution when hunting
      shifted to farming. Prior to the establishment of the commercial European pig
      breeds we know today, some 200 years ago Chinese pigs were imported into Europe
      to improve local European pigs. Commercial European domesticated pigs are
      genetically more diverse than European wild boars, although historically the
      latter represents the source population for domestication. In this study we
      examine the cause of the higher diversity within the genomes of European
      commercial pigs compared to their wild ancestors by testing two different
      hypotheses. In the first hypothesis we consider that European commercial pigs are
      a mix of different European wild populations as a result of movement throughout
      Europe, hereby acquiring haplotypes from all over the European continent. As an
      alternative hypothesis, we examine whether the introgression of Asian haplotypes
      into European breeds during the Industrial Revolution caused the observed
      increase in diversity. By using re-sequence data for chromosome 1 of 136 pigs and
      wild boars, we show that an Asian introgression of about 20% into the genome of
      European commercial pigs explains the majority of the increase in genetic
      diversity. These findings confirm that the Asian hybridization, that was used to
      improve production traits of local breeds, left its signature in the genome of
      the commercial pigs we know today. 

PMID- 25601876
TI  - Serpentine bacteria influence metal translocation and bioconcentration of
      Brassica juncea and Ricinus communis grown in multi-metal polluted soils.
AB  - The aim of this study was to assess the effects of inoculation of rhizosphere or
      endophytic bacteria (Psychrobacter sp. SRS8 and Pseudomonas sp. A3R3,
      respectively) isolated from a serpentine environment on the plant growth and the
      translocation and accumulation of Ni, Zn, and Fe by Brassica juncea and Ricinus
      communis on a multi-metal polluted serpentine soil (SS). Field collected SS was
      diluted to 0, 25, 50, and 75% with pristine soil in order to obtain a range of
      heavy metal concentrations and used in microcosm experiments. Regardless of
      inoculation with bacteria, the biomass of both plant species decreased with
      increase of the proportion of SS. Inoculation of plants with bacteria
      significantly increased the plant biomass and the heavy metal accumulation
      compared with non-inoculated control in the presence of different proportion of
      SS, which was attributed to the production of plant growth promoting and/or metal
      mobilizing metabolites by bacteria. However, SRS8 showed a maximum increase in
      the biomass of the test plants grown even in the treatment of 75% SS. In turn,
      A3R3 showed maximum effects on the accumulation of heavy metals in both plants.
      Regardless of inoculation of bacteria and proportion of SS, both plant species
      exhibited low values of bioconcentration factor (<1) for Ni and Fe. The
      inoculation of both bacterial strains significantly increased the translocation
      factor (TF) of Ni while decreasing the TF of Zn in both plant species. Besides
      this contrasting effect, the TFs of all metals were <1, indicating that all
      studied bacteria-plant combinations are suitable for phytostabilization. This
      study demonstrates that the bacterial isolates A3R3 and SRS8 improved the growth
      of B. juncea and R. communis in SS soils and have a great potential to be used as
      inoculants in phytostabilization scenarios of multi-metal contaminated soils. 

PMID- 25601879
TI  - Neotropical mammal diversity and the Great American Biotic Interchange: spatial
      and temporal variation in South America's fossil record.
AB  - The vast mammal diversity of the Neotropics is the result of a long evolutionary
      history. During most of the Cenozoic, South America was an island continent with
      an endemic mammalian fauna. This isolation ceased during the late Neogene after
      the formation of the Isthmus of Panama, resulting in an event known as the Great
      American Biotic Interchange (GABI). In this study, we investigate biogeographic
      patterns in South America, just before or when the first immigrants are recorded
      and we review the temporal and geographical distribution of fossil mammals during
      the GABI. We performed a dissimilarity analysis which grouped the faunal
      assemblages according to their age and their geographic distribution. Our data
      support the differentiation between tropical and temperate assemblages in South
      America during the middle and late Miocene. The GABI begins during the late
      Miocene (~10-7 Ma) and the putative oldest migrations are recorded in the
      temperate region, where the number of GABI participants rapidly increases after
      ~5 Ma and this trend continues during the Pleistocene. A sampling bias toward
      higher latitudes and younger records challenges the study of the temporal and
      geographic patterns of the GABI. 

PMID- 25601881
TI  - Disseminated cysticercosis.

PMID- 25601880
TI  - Ethical, legal and social implications of incorporating personalized medicine
      into healthcare.
AB  - As research focused on personalized medicine has developed over the past decade,
      bioethics scholars have contemplated the ethical, legal and social implications
      of this type of research. In the next decade, there will be a need to broaden the
      focus of this work as personalized medicine moves into clinical settings. We
      consider two broad issues that will grow in importance and urgency. First, we
      analyze the consequences of the significant increase in health information that
      will be brought about by personalized medicine. Second, we raise concerns about
      the potential of personalized medicine to exacerbate existing disparities in
      healthcare.

PMID- 25601882
TI  - Levamisole-induced leukoencephalopathy mimicking Balo disease.

PMID- 25601885
TI  - Influence of hospital-level practices on readmission after ischemic stroke.

PMID- 25601884
TI  - Joint effect of mid- and late-life blood pressure on the brain: the AGES
      Reykjavik Study.

PMID- 25601883
TI  - Pyridoxine responsiveness in novel mutations of the PNPO gene.

PMID- 25601886
TI  - Pearls & Oy-sters: Pisa syndrome: an unusual feature of adult-onset fulminant
      SSPE.

PMID- 25601887
TI  - Teaching NeuroImages: the lentiform fork sign: an MRI pattern of metformin
      associated encephalopathy.

PMID- 25601888
TI  - Breastfeeding in public: "You can do it?".
AB  - On a regular basis there is an outcry about a mother who has been told to cover
      up or move away from a public area while she is breastfeeding. Mothers should
      feel free to breastfeed whenever they need to. However, the increasing market for
      "nursing covers" to hide the breast while feeding is evidence of changing
      perceptions. Discomfort with the idea of breastfeeding in public has been cited
      as a reason for some women choosing not to initiate breastfeeding or planning a
      shorter duration of breastfeeding. Other women are choosing to express and bottle
      feed their expressed milk when they are in public. In many cultures today there
      is a conflict between the concept of breast milk being pure (like tears), and
      contaminated or "dirty" (like genital secretions or vomit). In these settings the
      female breast may be considered primarily a sexual organ, and therefore a private
      part of the body, which needs to be invisible in the public arena. In order to
      increase breastfeeding initiation and duration and to reduce health inequities
      breastfeeding needs to be more visible. Let's strive together to make
      breastfeeding in public unremarkable. 

PMID- 25601890
TI  - Giant molluscum contagiosum: an unusual presenting complaint of paediatric HIV
      disease.
AB  - We report a widely disseminated, disfiguring facial molluscum contagiosum (MC) as
      a presenting complaint in an 11-year-old girl secondary to human immune
      deficiency virus infection. A biopsy specimen demonstrated lobulated epidermal
      growth consisting of keratinocytes with large intracytoplasmic eosinophilic
      inclusion bodies. The patient was treated with highly active anti-retroviral
      therapy (HAART). The extent of MC in our patient was remarkable and subsequently
      improved dramatically after starting HAART. Normally MC does not similarly
      respond in patients with AIDS. 

PMID- 25601889
TI  - A health economic evaluation of screening and treatment in patients with
      adolescent idiopathic scoliosis.
AB  - SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis can progress and
      affect the health related quality of life of the patients. Research shows that
      screening is effective in early detection, which allows for bracing and reduced
      surgical rates, and may save costs, but is still controversial from a health
      economic perspective. STUDY DESIGN: Model based cost minimisation analysis using
      hospital's costs, administrative data, and market prices to estimate costs in
      screening, bracing and surgical treatment. Uncertainty was characterised by
      deterministic and probabilistic sensitivity analyses. Time horizon was 6 years
      from first screening at 11 years of age. OBJECTIVE: To compare estimated costs in
      screening and non-screening scenarios (reduced treatment rates of 90%, 80%, 70%
      of screening, and non-screening Norway 2012). METHODS: Data was based on
      screening and treatment costs in primary health care and in hospital care
      settings. Participants were 4000, 12-year old children screened in Norway, 115190
      children screened in Hong Kong and 112 children treated for scoliosis in Norway
      in 2012. We assumed equivalent outcome of health related quality of life, and
      compared only relative costs in screening and non-screening settings. Incremental
      cost was defined as positive when a non-screening scenario was more expensive
      relative to screening. RESULTS: Screening per child was ? 8.4 (95% CrI 6.6
      to10.6), ? 10350 (8690 to 12180) per patient braced, and ? 45880 (39040 to 55400)
      per child operated. Incremental cost per child in non-screening scenario of 90%
      treatment rate was ? 13.3 (1 to 27), increasing from ? 1.3 (-8 to 11) to ? 27.6
      (14 to 44) as surgical rates relative to bracing increased from 40% to 80%. For
      the 80% treatment rate non-screening scenario, incremental cost was ? 5.5 (-6 to
      18) when screening all, and ? 11.3 (2 to 22) when screening girls only. For the
      non-screening Norwegian scenario, incremental cost per child was ? -0.1(-14 to
      16). Bracing and surgery were the main cost drivers and contributed most to
      uncertainty. CONCLUSIONS: With the assumptions applied in the present study,
      screening is cost saving when performed in girls only, and when it leads to
      reduced treatment rates. Cost of surgery was dominating in non-screening whilst
      cost of bracing was dominating in screening. The economic gain of screening
      increases when it leads to higher rates of bracing and reduced surgical rates.

PMID- 25601891
TI  - Expression of bcl-2 and p53 in bovine cutaneous fibropapillomas.
AB  - BACKGROUND: Bovine cutaneous fibropapillomas are benign hyperproliferative
      lesions induced by Bovine Papillomaviruses (BPVs). Bcl-2 is an important anti
      apoptotic protein which is expressed in several cancer types. In contrary, p53 is
      a tumour suppressor protein that mediates cell cycle arrest, apoptosis and
      senescence in response to cellular stresses. FINDINGS: Here, we investigated
      immunohistochemically and biochemically, the expression of bcl-2 and p53 in a
      subset of BPV positive fibropapillomas and bovine normal skin. Normal skin
      samples showed a weak signal for both proteins in the cytoplasm of the basal
      cells. Nine out of twelve (75%) tumour samples stained positive for bcl-2
      throughout basal and parabasal layers, with most of cells showing strong
      cytoplasmic immunoreactivity. Nine out of twelve (75%) fibropapillomas were found
      to be positive for p53 expression, showing a strong cytoplasmic and perinuclear
      staining of p53 protein mainly in the basal and parabasal layers. CONCLUSIONS:
      Our data reveal an altered bcl-2 and p53 immunoreactivity in bovine cutaneous
      fibropapillomas, suggesting involvement of these two proteins in the cutaneous
      neoplastic transformation through an impaired apoptotic process.

PMID- 25601892
TI  - Existing public health surveillance systems for mental health in China.
AB  - Mental health is a challenging public health issue worldwide and surveillance is
      crucial for it. However, mental health surveillance has not been developed until
      recently in certain developed countries; many other countries, especially
      developing countries, have poor or even no health information systems. This paper
      presents surveillance related to mental health in China, a developing country
      with a large population of patients with mental disorders. Detailed information
      of seven relevant surveillance systems is introduced respectively. From the
      perspective of utilization, problems including accessibility, comprehensiveness
      and data quality are discussed. Suggestions for future development are proposed. 

PMID- 25601893
TI  - How Do Management Fees Affect Retirement Wealth under Mexico's Personal
      Retirement Accounts System?
AB  - In 1997, Mexico transformed its pay-as-you-go social security system to a fully
      funded system with personal retirement accounts, including management fees. This
      article examines changes in retirement wealth resulting from this new system. It
      shows that management fees have drained a significant proportion of individuals'
      retirement wealth and have increased the number of persons claiming a government
      subsidized minimum pension, particularly from the time the system was introduced
      in 1997 until adjustment to management fees in 2008. Since 2008, retirement
      wealth accumulation has been similar to that of the previous system. En 1997,
      Mexico transformo su sistema de pensiones basado en cotizaciones individuales a
      uno de ahorro para el retiro que incluyen cuotas por la administracion de las
      cuentas. El presente estudio examina los cambios en el monto de las pensiones
      como resultado de la introduccion del nuevo sistema. Los resultados muestran que
      las cuotas de administracion han drenado una proporcion significativa del ahorro
      para el retiro de los individuos por lo que ha aumentado el numero de personas
      que solicita la pension minima garantizada subsidiada por el gobierno desde que
      se introdujo el sistema en 1997 hasta que se hicieron ajustes en las cuotas de
      administracion de los fondos de pensiones en 2008. A partir de 2008, la
      acumulacion del ahorro para el retiro ha sido similar que la del sistema
      anterior.

PMID- 25601894
TI  - Microinjection of specific anti-IMPDH2 antibodies induces disassembly of
      cytoplasmic rods/rings that are primarily stationary and stable structures.
AB  - BACKGROUND: Our laboratory previously reported interesting rods 3-10 MUm long and
      rings 2-5 MUm diameter (RR) in the cytoplasm of mammalian cells. Experimental
      evidence show that both inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and
      cytidine triphosphate synthetase (CTPS) are components of RR structures. Several
      cell types, including mouse embryonic stem cells, and cell lines, such as mouse 3
      T3 and rat NRK, naturally present RR structures, while other cells can present RR
      when treated with compounds interfering with GTP/CTP biosynthetic pathways. In
      this study, we aimed to investigate the dynamic behavior of these RR in live
      cells. RESULTS: RR were detected in >90% of COS-7 and HeLa cells treated with 1
      mM ribavirin or 6-Diazo-5-oxo-L-norleucine (DON) for 24 h, and in 75% of COS-7
      cells treated with 1 mM mycophenolic acid (MPA) for the same period of time.
      Microinjection of affinity-purified anti-IMPDH2 antibodies in live COS-7 cells
      treated with ribavirin, DON, or MPA showed mature forms of RR presented as stable
      and stationary structures in 71% of cells. In the remaining 29% of cells, RR
      acquired erratic movement and progressively disassembled into fragments and
      disappeared within 10 min. The specific stationary state and antibody-dependent
      disassembling of RR structures was independently confirmed in COS-7 and HeLa
      cells transfected with GFP-tagged IMPDH2. CONCLUSIONS: This is the first
      demonstration of disassembly of RR structures upon microinjection of anti-IMPDH2
      antibodies that led to the disappearance of the molecular aggregates. The
      disassembly of RR after microinjection of anti-IMPDH2 antibody further
      strengthens the notion that IMPDH2 are major building blocks of RR. Using two
      independent methods, this study demonstrated that the induced RR are primarily
      stationary structures in live cells and that IMPDH2 is a key component of RR.

PMID- 25601895
TI  - Elevated Levels of LDL-C are Associated With ApoE4 but Not With the rs688
      Polymorphism in the LDLR Gene.
AB  - INTRODUCTION: Apolipoprotein E (ApoE) 4 isoform has been associated with elevated
      levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), and
      triglycerides (TGs), meanwhile several polymorphisms in the LDL receptor (LDLR)
      gene have been associated with increased levels of total cholesterol and LDL-C.
      MATERIAL AND METHODS: We studied 400 women from Southwest Mexico. Anthropometric
      features and biochemical profile were evaluated, and genotyping of single
      nucleotide polymorphisms rs429358 and rs7412 in the APOE gene and rs688 in the
      LDLR gene was determined by TaqMan assays. RESULTS: We found significant
      association between LDL-C (odds ratio [OR] = 3.3, 95% confidence interval [CI]:
      1.9-5.7) and marginal association with TG (OR = 1.7, 95% CI: 1.0-2.9) of
      atherogenic risk in women carriers of the ApoE4 isoform compared to ApoE3. The TT
      genotype of rs688 in the LDLR gene was not found to be associated with elevated
      levels of total cholesterol or LDL-C. CONCLUSION: Our results show that carrier
      women of the ApoE4 isoform are more likely to have elevated levels of LDL-C and
      therefore increased risk of developing atherosclerosis.

PMID- 25601896
TI  - The Effect of High-Dose Vitamin D3 on Soluble P-Selectin and hs-CRP Level in
      Patients With Venous Thromboembolism: A Randomized Clinical Trial.
AB  - High plasma level of P-selectin is associated with the development of venous
      thromboembolism (VTE). Furthermore, supplementation of vitamin D could decrease
      thrombotic events. Hence, this study was designed to examine whether the
      administration of vitamin D can influence the plasma level of P-selectin in
      patients with VTE. In the randomized controlled trial, 60 patients with confirmed
      acute deep vein thrombosis and/or pulmonary embolism (PE) were randomized into
      the intervention (n = 20) and control (n = 40) groups. The intervention arm was
      given an intramuscular single dose of 300 000 IU vitamin D3 Plasma level of 25
      hydroxy vitamin D, P-selectin, and high-sensitive C-reactive protein (hs-CRP) was
      measured at baseline and 4 weeks after. The plasma level of P-selectin (95%
      confidence interval = -5.99 to -1.63, P = .022) and hs-CRP (P = .024)
      significantly declined in vitamin D-treated group, while only hs-CRP was
      significantly decreased in the control group (P = .011). However, the magnitude
      of these reductions was not statistically significant. This study could not
      support the potential benefit of the high-dose vitamin D on plasma level of P
      selectin and hs-CRP in patients with VTE. 

PMID- 25601897
TI  - Modulation of Sickle Red Blood Cell Adhesion and its Associated Changes in
      Biomarkers by Sulfated Nonanticoagulant Heparin Derivative.
AB  - Abnormal cellular adhesion is one of the primary causes of vaso-occlusive crisis
      in sickle cell disease (SCD). Levels of intercellular adhesion molecule 1 (ICAM
      1) and P-selectin are upregulated, resulting in increased adhesion of leukocytes
      and sickle red blood cells (RBCs) to endothelium. This study compares the
      inhibitory effect of a sulfated nonanticoagulant heparin (S-NACH) derivative with
      a low-molecular-weight heparin, tinzaparin, on the adhesion of sickle RBCs to
      endothelium. The S-NACH exhibits minimum effects on hemostasis and bleeding and
      interferes with the binding of pancreatic cancer cells to endothelial cells via P
      selectin. We show by static binding assay that pretreatment of both erythrocytes
      and endothelial cells with S-NACH significantly inhibits the increased adhesion
      of sickle RBCs to endothelial cells. The S-NACH treatment also decreases the
      higher plasma levels of (adhesion biomarkers) ICAM-1 and P-selectin in SCD mice.
      This investigation signals further research into the potential use of S-NACH in
      treating vaso-occlusions with minimal bleeding events in patients with SCD. 

PMID- 25601899
TI  - Leukocyte infiltration across the blood-spinal cord barrier is modulated by sleep
      fragmentation in mice with experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: We have recently shown that mice with experimental autoimmune
      encephalomyelitis (EAE) have increased sleep fragmentation (SF) and reduced sleep
      efficiency, and that the extent of SF correlates with the severity of disease. It
      is not yet clear whether and how sleep promotes recovery from autoimmune attacks.
      We hypothesized that SF promotes leukocyte infiltration across the blood-spinal
      cord barrier, impairs immune regulation, and thus worsens EAE. METHODS: Three
      groups of C57 mice were studied: Resting EAE; SF EAE with the mice subjected to
      the SF maneuver 12 h /day during zeitgeber time (ZT) 0-12 h; and naive controls
      with neither EAE nor SF. Besides monitoring of the incidence and severity of EAE,
      the immune profiles of leukocytes in the spinal cord as well as those in the
      spleen were determined. RESULTS: When analyzed 16 days after EAE induction, at
      which time the SF was terminated, the SF group had a greater number of CD4(+) T
      cells and a higher percent of CD4(+) cells among all leukocytes in the spinal
      cord than the resting EAE group. When allowed to recover to 28 days after EAE
      induction, the SF mice had lower EAE scores than the resting EAE group. EAE
      induced splenomegaly and an increase of Gr1(+)CD11b(+) myeloid-derived suppressor
      cells in the splenocytes. However, SF treatment had no additional effect on
      either peripheral splenocytes or granulocytes that reached the spinal cord.
      CONCLUSION: The SF maneuver facilitated the migration of encephalopathic
      lymphocytes into the spinal cord. Paradoxically, these mice had a better EAE
      score after cessation of SF compared with mice without SF.

PMID- 25601898
TI  - Evaluation and Pharmacokinetics of Treatment Dose Enoxaparin in Hospitalized
      Patients With Morbid Obesity.
AB  - BACKGROUND: The pharmacokinetic properties of enoxaparin may lead to
      supratherapeutic antifactor Xa (anti-Xa) levels and increased bleeding when
      standard treatment doses are used in patients with morbid obesity. OBJECTIVE: To
      evaluate the dose of enoxaparin needed to achieve therapeutic anti-Xa levels in a
      prospective, masked observational cohort of heterogeneous inpatients with morbid
      obesity and to determine whether patients with morbid obesity treated with 1
      mg/kg of enoxaparin are at increased risk of supratherapeutic levels and bleeding
      events compared to patients receiving lower doses. METHODS: Hospitalized patients
      with a body mass index >=40 kg/m(2) or actual body weight >=140 kg and prescribed
      treatment doses of enoxaparin >60 mg per day were enrolled and consented to
      phlebotomy for determination of anti-Xa levels. RESULTS: Forty-one patients were
      included for data analysis. The dose of enoxaparin that resulted in therapeutic
      and supratherapeutic anti-Xa levels at steady state was 0.83 mg/kg and 0.98 mg/kg
      (-0.11; 95% confidence interval [CI] -0.20 to -0.01, P = .02), respectively.
      Enoxaparin dose as mg/kg of actual body weight was an independent predictor of
      having a supratherapeutic anti-Xa level. Patients with doses <0.95 mg/kg versus
      >=0.95 mg/kg were less likely to have supratherapeutic levels (odds ratio 0.21
      [95% CI 0.05-0.84], P = .02) and had similar rates of subtherapeutic levels.
      Doses <0.95 mg/kg and >=0.95 mg/kg resulted in similar bleeding rates of 17.9%
      and 22.2% (P = .71), respectively. CONCLUSION: Patients with morbid obesity
      required less than the recommended 1 mg/kg enoxaparin dose to achieve therapeutic
      peak anti-Xa levels; therefore, initiation with lower dosages is prudent and anti
      Xa monitoring should guide dosage adjustments.

PMID- 25601900
TI  - Comparative study of the effect of rivaroxaban and fondaparinux on monocyte's
      coagulant activity and cytokine release.
AB  - OBJECTIVES: Tissue factor (TF) exposed on activated monocytes and macrophages is
      involved in thrombosis through activation of factor X and cytokine release,
      responsible for inflammation and thrombosis. We investigated the effect of two
      anti-factor Xa drugs: rivaroxaban, a direct anti-Xa inhibitor, and fondaparinux,
      an antithrombin dependent anti-Xa inhibitor, on monocyte/macrophage procoagulant
      activity and cytokine release. METHODS: Rivaroxaban and fondaparinux were tested
      at pharmacological concentrations on LPS-activated monocytes and on THP-1 cells,
      a human monocytic cell line, to assess 1) TF expression by flow cytometry 2)
      prothrombinase activity by its coagulant activity and 3) cytokine release in cell
      supernatants by antibody based cytokine array and ELISA for IL-8 and TNFalpha.
      RESULTS AND CONCLUSION: Rivaroxaban and fondaparinux did not modify TF expression
      level on activated cells. In contrast procoagulant activity associated to
      monocytes and macrophages was dose dependently inhibited by rivaroxaban, but not
      significantly by fondaparinux. These results could explain why patients
      undergoing major orthopedic surgery with rivaroxaban prophylaxis were able to
      achieve significant reductions in venous thromboembolism, compared with drugs
      commonly used, i.e. fondaparinux and low molecular weight heparin. In addition,
      rivaroxaban and fondaparinux suppressed some chemokine secretion produced by
      activated macrophages. This may also contribute to their antithrombotic effect in
      clinic.

PMID- 25601902
TI  - Optimizing the detection of venous invasion in colorectal cancer: the ontario,
      Canada, experience and beyond.
AB  - Venous invasion (VI) is a well-established independent prognostic indicator in
      colorectal cancer (CRC). Its accurate detection is particularly important in
      stage II CRC as it may influence the decision to administer adjuvant therapy. The
      Royal College of Pathologists (RCPath) of the United Kingdom state that VI should
      be detected in at least 30% of CRC resection specimens. However, our experience
      in Ontario, Canada suggests that this (conservative) benchmark is rarely met.
      This article highlights the "Ontario experience" with respect to VI reporting and
      the key role that careful morphologic assessment, elastin staining and knowledge
      transfer has played in improving VI detection provincially and beyond. 

PMID- 25601901
TI  - Notching on Cancer's Door: Notch Signaling in Brain Tumors.
AB  - Notch receptors play an essential role in the regulation of central cellular
      processes during embryonic and postnatal development. The mammalian genome
      encodes for four Notch paralogs (Notch 1-4), which are activated by three Delta
      like (Dll1/3/4) and two Serrate-like (Jagged1/2) ligands. Further, non-canonical
      Notch ligands such as epidermal growth factor like protein 7 (EGFL7) have been
      identified and serve mostly as antagonists of Notch signaling. The Notch pathway
      prevents neuronal differentiation in the central nervous system by driving neural
      stem cell maintenance and commitment of neural progenitor cells into the glial
      lineage. Notch is therefore often implicated in the development of brain tumors,
      as tumor cells share various characteristics with neural stem and progenitor
      cells. Notch receptors are overexpressed in gliomas and their oncogenicity has
      been confirmed by gain- and loss-of-function studies in vitro and in vivo. To
      this end, special attention is paid to the impact of Notch signaling on stem-like
      brain tumor-propagating cells as these cells contribute to growth, survival,
      invasion, and recurrence of brain tumors. Based on the outcome of ongoing studies
      in vivo, Notch-directed therapies such as gamma-secretase inhibitors and blocking
      antibodies have entered and completed various clinical trials. This review
      summarizes the current knowledge on Notch signaling in brain tumor formation and
      therapy.

PMID- 25601903
TI  - The Tumor Cytosol miRNAs, Fluid miRNAs, and Exosome miRNAs in Lung Cancer.
AB  - The focus of this review is to provide an update on the progress of microRNAs
      (miRNAs) as potential biomarkers for lung cancer. miRNAs are single-stranded,
      small non-coding RNAs that regulate gene expression and show tissue-specific
      signatures. Accumulating evidence indicates that miRNA expression patterns
      represent the in vivo status in physiology and disease. Moreover, miRNAs are
      stable in serum and other clinically convenient and available tissue sources, so
      they are being developed as biomarkers for cancer and other diseases. Cancer is
      currently the primary driver of the field, but miRNA biomarkers are being
      developed for many other diseases such as cardiovascular and central nervous
      system diseases. Here, we examine the framework and scope of the miRNA landscape
      as it specifically relates to the translation of miRNA expression
      patterns/signatures into biomarkers for developing diagnostics for lung cancer.
      We focus on examining tumor cytosol miRNAs, fluid miRNAs, and exosome miRNAs in
      lung cancer, the connections among these miRNAs, and the potential of miRNA
      biomarkers for the development of diagnostics. In lung cancer, miRNAs have been
      studied in both cell populations and in the circulation. However, a major
      challenge is to develop biomarkers to monitor cancer development and to identify
      circulating miRNAs that are linked to cancer stage. Importantly, the fact that
      miRNAs can be successfully harvested from biological fluids allows for the
      development of biofluid biopsies, in which miRNAs as circulating biomarkers can
      be captured and analyzed ex vivo. Our hope is that these minimally invasive
      entities provide a window to the in vivo milieu of the patients without the need
      for costly, complex invasive procedures, rapidly moving miRNAs from research to
      the clinic. 

PMID- 25601904
TI  - P-Cadherin Linking Breast Cancer Stem Cells and Invasion: A Promising Marker to
      Identify an "Intermediate/Metastable" EMT State.
AB  - Epithelial-mesenchymal transition (also known as EMT) is a fundamental mechanism
      occurring during embryonic development and tissue differentiation, being also
      crucial for cancer progression. Actually, the EMT program contributes to the
      dissemination of cancer cells from solid tumors and to the formation of micro
      metastasis that subsequently develop into clinically detectable metastases.
      Besides being a process that is defined by the progressive loss of epithelial
      cell characteristics and the acquisition of mesenchymal features, EMT has also
      been implicated in therapy resistance, immune escape, and maintenance of cancer
      stem cell properties, such as self-renewal capacity. However, the majority of the
      studies usually neglect the progressive alterations occurring during intermediate
      EMT states, which imply a range of phenotypic cellular heterogeneity that can
      potentially generate more metastable and plastic tumor cells. In fact, few
      studies have tried to identify these transitory states, partly due to the current
      lack of a detailed understanding of EMT, as well as of reliable readouts for its
      progression. Herein, a brief review of evidences is presented, showing that P
      cadherin expression, which has been already identified as a breast cancer stem
      cell marker and invasive promoter, is probably able to identify an intermediate
      EMT state associated with a metastable phenotype. This hypothesis is based on our
      own work, as well as on the results described by others, which suggest the use of
      P-cadherin as a promising EMT marker, clearly functioning as an important
      clinical prognostic factor and putative therapeutic target in breast
      carcinogenesis. 

PMID- 25601906
TI  - Undergraduate training in public health should prepare graduates for the
      workforce.

PMID- 25601905
TI  - Radon sources and associated risk in terms of exposure and dose.
AB  - Radon concerns the international scientific community from the early twentieth
      century, initially as radium emanation and nearly the second half of the century
      as a significant hazard to human health. The initial brilliant period of its use
      as medicine was followed by a period of intense concern for its health effects.
      Miners in Europe and later in the U.S were the primary target groups surveyed.
      Nowadays, there is a concrete evidence that radon and its progeny can cause lung
      cancer (1). Human activities may create or modify pathways increasing indoor
      radon concentration compared to outdoor background. These pathways can be
      controlled by preventive and corrective actions (2). Indoor radon and its short
      lived progeny either attached on aerosol particles or free, compose an air
      mixture that carries a significant energy amount [Potential Alpha-Energy
      Concentration (PAEC)]. Prior research at that topic focused on the exposure on
      PAEC and the dose delivered by the human body or tissues. Special mention was
      made to the case of water workers due to inadequate data. Furthermore, radon risk
      assessment and relevant legislation for the dose delivered by man from radon and
      its progeny has been also reviewed. 

PMID- 25601907
TI  - Developing leaders: implementation of a peer advising program for a public health
      sciences undergraduate program.
AB  - Peer advising is an integral part of our undergraduate advising system in the
      Public Health Sciences major at the University of Massachusetts Amherst. The
      program was developed in 2009 to address the advising needs of a rapidly growing
      major that went from 25 to over 530 majors between 2007 and 2014. Each year, 9-12
      top performing upper-level students are chosen through an intensive application
      process. A major goal of the program is to provide curriculum and career guidance
      to students in the major and empower students in their academic and professional
      pursuits. The year-long program involves several components, including: staffing
      the drop-in advising center, attending training seminars, developing and
      presenting workshops for students, meeting prospective students and families,
      evaluating ways to improve the program, and collaborating on self-directed
      projects. The peer advisors (PAs) also provide program staff insight into the
      needs and perspectives of students in the major. In turn, PAs gain valuable
      leadership and communication skills, and learn strategies for improving student
      success. The Peer Advising Program builds community and fosters personal and
      professional development for the PAs. In this paper, we will discuss the
      undergraduate peer advising model, the benefits and challenges of the program,
      and lessons learned. Several methods were used to understand the perceived
      benefits and challenges of the program and experiences of students who utilized
      the Peer Advising Center. The data for this evaluation were drawn from three
      sources: (1) archival records from the Peer Advising Center; (2) feedback from
      PAs who completed the year-long internship; and (3) a survey of students who
      utilized the Peer Advising Center. Results of this preliminary evaluation
      indicate that PAs gain valuable skills that they can carry into their
      professional world. The program is also a way to engage students in building
      community within the major. 

PMID- 25601908
TI  - Determination of genotoxic effects of fipronil in Vicia faba using random
      amplified polymorphic DNA analysis.
AB  - This study was undertaken to appreciate genotoxic potential of fipronil
      herbicides in the roots of Vicia faba seedlings. Fipronil was clearly dose
      dependent on root growth inhibitors, total soluble protein, and random amplified
      polymorphic DNA (RAPD) assays. Increase in concentration of fipronil resulted in
      decreased amount of root length and increased level of protein. For the RAPD
      analyses, 15 RAPD primers were found to produce unique polymorphic band patterns
      and were subsequently used to produce a total of 110 bands of 45-1250 bp. Each
      primer generated 4-11 RAPD bands across 15 primers. The changes occurring in RAPD
      profiles following fipronil treatment included variation becoming evident as
      disappearance and/or appearance of DNA bands compared with the normal seedlings.
      These results indicated that genomic template stability was significantly
      affected at the above fipronil concentration. This study further confirmed that
      the RAPD assays are useful in determining potential genotoxicity of fipronil.

PMID- 25601909
TI  - Total synthesis of natural products using hypervalent iodine reagents.
AB  - We present a review of natural product syntheses accomplished in our laboratory
      during the last 5 years. Each synthetic route features a phenol dearomatization
      promoted by an environmentally benign hypervalent iodine reagent. The
      dearomatizations demonstrate the "aromatic ring umpolung" concept, and involve
      stereoselective remodeling of the inert unsaturations of a phenol into a highly
      functionalized key intermediate that may contain a quaternary carbon center and a
      prochiral dienone system. Several new oxidative strategies were employed,
      including transpositions (1,3-alkyl shift and Prins-pinacol), a polycyclization,
      an ipso rearrangement, and direct nucleophilic additions at the phenol para
      position. Several alkaloids, heterocyclic compounds, and a polycyclic core have
      been achieved, including sceletenone (a serotonin reuptake inhibitor),
      acetylaspidoalbidine (an antitumor agent), fortucine (antiviral and antitumor),
      erysotramidine (curare-like effect), platensimycin (an antibiotic), and the main
      core of a kaurane diterpene (immunosuppressive agent and stimulator of
      apoptosis). These concise and in some cases enantioselective syntheses
      effectively demonstrate the importance of hypervalent iodine reagents in the
      total synthesis of bioactive natural products. 

PMID- 25601911
TI  - Using CellML with OpenCMISS to Simulate Multi-Scale Physiology.
AB  - OpenCMISS is an open-source modeling environment aimed, in particular, at the
      solution of bioengineering problems. OpenCMISS consists of two main parts: a
      computational library (OpenCMISS-Iron) and a field manipulation and visualization
      library (OpenCMISS-Zinc). OpenCMISS is designed for the solution of coupled multi
      scale, multi-physics problems in a general-purpose parallel environment. CellML
      is an XML format designed to encode biophysically based systems of ordinary
      differential equations and both linear and non-linear algebraic equations. A
      primary design goal of CellML is to allow mathematical models to be encoded in a
      modular and reusable format to aid reproducibility and interoperability of
      modeling studies. In OpenCMISS, we make use of CellML models to enable users to
      configure various aspects of their multi-scale physiological models. This avoids
      the need for users to be familiar with the OpenCMISS internal code in order to
      perform customized computational experiments. Examples of this are: cellular
      electrophysiology models embedded in tissue electrical propagation models;
      material constitutive relationships for mechanical growth and deformation
      simulations; time-varying boundary conditions for various problem domains; and
      fluid constitutive relationships and lumped-parameter models. In this paper, we
      provide implementation details describing how CellML models are integrated into
      multi-scale physiological models in OpenCMISS. The external interface OpenCMISS
      presents to users is also described, including specific examples exemplifying the
      extensibility and usability these tools provide the physiological modeling and
      simulation community. We conclude with some thoughts on future extension of
      OpenCMISS to make use of other community developed information standards, such as
      FieldML, SED-ML, and BioSignalML. Plans for the integration of accelerator code
      (graphical processing unit and field programmable gate array) generated from
      CellML models is also discussed. 

PMID- 25601912
TI  - Initiation of antiretroviral therapy and viral suppression after home HIV testing
      and counselling in KwaZulu-Natal, South Africa, and Mbarara district, Uganda: a
      prospective, observational intervention study.
AB  - OBJECTIVE: Antiretroviral therapy (ART) significantly decreases HIV-associated
      morbidity, mortality, and HIV transmission through HIV viral load suppression. In
      high HIV prevalence settings, outreach strategies are needed to find asymptomatic
      HIV positive persons, link them to HIV care and ART, and achieve viral
      suppression. METHODS: We conducted a prospective intervention study in two rural
      communities in KwaZulu-Natal, South Africa, and Mbabara district, Uganda. The
      intervention included home HIV testing and counseling (HTC), point-of-care CD4
      count testing for HIV positive persons, referral to care, and one month then
      quarterly lay counselor follow-up visits. The outcomes at 12 months were linkage
      to care, and ART initiation and viral suppression among HIV positive persons
      eligible for ART (CD4<=350 cells/MUL). FINDINGS: 3,393 adults were tested for HIV
      (96% coverage), of whom 635 (19%) were HIV positive. At baseline, 36% of HIV
      positive persons were newly identified (64% were previously known to be HIV
      positive) and 40% were taking ART. By month 12, 619 (97%) of HIV positive persons
      visited an HIV clinic, and of 123 ART eligible participants, 94 (76%) initiated
      ART by 12 months. Of the 77 participants on ART by month 9, 59 (77%) achieved
      viral suppression by month 12. Among all HIV positive persons, the proportion
      with viral suppression (<1,000 copies/mL) increased from 50% to 65% (p=<0.001) at
      12 months. INTERPRETATION: Community-based HTC in rural South Africa and Uganda
      achieved high testing coverage and linkage to care. Among those eligible for ART,
      a high proportion initiated ART and achieved viral suppression, indicating high
      adherence. Implementation of this HTC approach by existing community health
      workers in Africa should be evaluated to determine effectiveness and costs.

PMID- 25601910
TI  - Succinate Overproduction: A Case Study of Computational Strain Design Using a
      Comprehensive Escherichia coli Kinetic Model.
AB  - Computational strain-design prediction accuracy has been the focus for many
      recent efforts through the selective integration of kinetic information into
      metabolic models. In general, kinetic model prediction quality is determined by
      the range and scope of genetic and/or environmental perturbations used during
      parameterization. In this effort, we apply the k-OptForce procedure on a kinetic
      model of E. coli core metabolism constructed using the Ensemble Modeling (EM)
      method and parameterized using multiple mutant strains data under aerobic
      respiration with glucose as the carbon source. Minimal interventions are
      identified that improve succinate yield under both aerobic and anaerobic
      conditions to test the fidelity of model predictions under both genetic and
      environmental perturbations. Under aerobic condition, k-OptForce identifies
      interventions that match existing experimental strategies while pointing at a
      number of unexplored flux re-directions such as routing glyoxylate flux through
      the glycerate metabolism to improve succinate yield. Many of the identified
      interventions rely on the kinetic descriptions that would not be discoverable by
      a purely stoichiometric description. In contrast, under fermentative (anaerobic)
      condition, k-OptForce fails to identify key interventions including up-regulation
      of anaplerotic reactions and elimination of competitive fermentative products.
      This is due to the fact that the pathways activated under anaerobic condition
      were not properly parameterized as only aerobic flux data were used in the model
      construction. This study shed light on the importance of condition-specific model
      parameterization and provides insight on how to augment kinetic models so as to
      correctly respond to multiple environmental perturbations. 

PMID- 25601913
TI  - Diversity and composition of the adult fecal microbiome associated with history
      of cesarean birth or appendectomy: Analysis of the American Gut Project.
AB  - BACKGROUND: Cesarean birth is associated with altered composition of the
      neonate's microbiota and with increased risk for obesity and other diseases later
      in life. The mechanisms of these associations, and whether cesarean birth is
      associated with an altered adult microbiota, are unknown. METHODS: In 1097 adult
      volunteers without diabetes, inflammatory bowel disease, or recent antibiotic
      use, fecal microbiome metrics were compared by history of cesarean birth (N=92)
      or appendectomy (N=115). Associations with potential confounders, microbiome
      alpha diversity, and individual microbial taxa were estimated by logistic
      regression. Permutation tests assessed differences in microbial composition (beta
      diversity) based on Jensen-Shannon divergence. FINDINGS: Cesarean birth history
      was associated with younger age; appendectomy with older age and higher body mass
      index. Neither was associated with fecal microbiome alpha diversity. Microbial
      composition at all taxonomic levels differed significantly with cesarean birth
      (P<=0.008) but not with appendectomy (P>=0.29). Relative abundance differed
      nominally for 17 taxa with cesarean birth and for 22 taxa with appendectomy, none
      of which was significant with adjustment for multiple comparisons.
      INTERPRETATION: Adults born by cesarean section appear to have a distinctly
      different composition of their fecal microbial population. Whether this
      distinction was acquired during birth, and whether it affects risk of disease
      during adulthood, are unknown.

PMID- 25601914
TI  - A cohort incidence study of workers exposed to perfluorooctanoic acid (PFOA).
AB  - OBJECTIVES: Determine if perfluorooctanoic acid (PFOA) is associated with an
      incident disease in an occupational cohort. METHODS: We interviewed 3713 workers
      or their next of kin in 2008-2011, and sought medical records for self-reported
      disease. These workers were a subset of a previously studied cohort of 32,254
      community residents and workers. We estimated historical PFOA serum levels via a
      job-exposure matrix based on over 2000 serum measurements. Non-occupational
      exposure from drinking water was also estimated. Lifetime serum cumulative dose
      (combining occupational and non-occupational exposure) was our exposure metric.
      We studied 17 disease outcomes with more than 20 validated cases. RESULTS: The
      median measured serum level was 113 ng/mL in 2005 (n=1881), compared with 4 ng/mL
      in the US. Ulcerative colitis (10-year lag) showed a significant trend (p<=0.05)
      with increasing dose (quartile rate ratios (RRs)=1.00, 3.00, 3.26, 6.57, n=28, p
      for trend=0.05), similar to earlier findings in the community study. Rheumatoid
      arthritis (no lag) showed a positive trend in a categorical trend test (RRs=1.00,
      2.11, 4.08, 4.45, n=23, p for trend=0.04). Positive non-significant trends were
      also observed for prostate cancer, non-hepatitis liver disease and male
      hypothyroidism, which have been implicated in other studies. A significant
      negative trend was found for bladder cancer and asthma with medication. No marked
      trends were seen for high cholesterol, which had been seen in the community
      study. CONCLUSIONS: Ulcerative colitis and rheumatoid arthritis were positively
      linked to PFOA exposure among workers. Data were limited by small numbers, under
      representation of hard-to-trace decedents and few low-exposed referents.

PMID- 25601916
TI  - Acetyl-l-carnitine versus placebo for migraine prophylaxis: A randomized, triple
      blind, crossover study.
AB  - BACKGROUND: Preventive medication is indicated for many migraine patients, but is
      used in relatively few. The aim of the present study was to evaluate the efficacy
      of acetyl-l-carnitine as a prophylactic drug in migraine patients. METHODS: A
      single-center, randomized, triple-blind, placebo-controlled, crossover study was
      carried out. Men and women, age 18-65 years, with episodic migraine but otherwise
      healthy, were recruited mostly through advertisements. After a four-week run-in
      phase, 72 participants were randomized to receive either placebo or 3 g acetyl-l
      carnitine for 12 weeks. After a four-week washout, treatment was switched. The
      primary outcome was days with moderate or severe headache per four weeks.
      Secondary outcomes were days with headache, hours with headache, proportion of
      responders (>50% reduction in migraine days from baseline) and adverse events.
      RESULTS: In the complete case analyses, no statistically significant differences
      were found between acetyl-l-carnitine and placebo in severe or moderate headache
      days per month (3.0 versus 3.1, p = 0.80), headache days per month (5.1 versus
      5.2, p = 0.73) or for the other secondary outcome measures. CONCLUSION: In this
      triple-blind crossover study no differences were found in headache outcomes
      between acetyl-l-carnitine and placebo. Our results do not provide evidence of
      benefit for efficacy of acetyl-l-carnitine as prophylactic treatment for
      migraine. TRIAL REGISTRATION: EUDRACT (2012-001624-36), ClinicalTrials.gov
      (NCT01695317).

PMID- 25601915
TI  - Meningeal norepinephrine produces headache behaviors in rats via actions both on
      dural afferents and fibroblasts.
AB  - BACKGROUND: Stress is commonly reported to contribute to migraine although
      mechanisms by which this may occur are not fully known. The purpose of these
      studies was to examine whether norepinephrine (NE), the primary sympathetic
      efferent transmitter, acts on processes in the meninges that may contribute to
      the pain of migraine. METHODS: NE was applied to rat dura using a behavioral
      model of headache. Primary cultures of rat trigeminal ganglia retrogradely
      labeled from the dura mater and of rat dural fibroblasts were prepared. Patch
      clamp electrophysiology, Western blot, and ELISA were performed to examine the
      effects of NE. Conditioned media from NE-treated fibroblast cultures was applied
      to the dura using the behavioral headache model. RESULTS: Dural injection both of
      NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw
      allodynia in awake rats. NE application to cultured dural afferents increased
      action potential firing in response to current injections. Application of NE to
      dural fibroblasts increased phosphorylation of ERK and caused the release of
      interleukin-6 (IL-6). CONCLUSIONS: These data demonstrate that NE can contribute
      to pro-nociceptive signaling from the meninges via actions on dural afferents and
      dural fibroblasts. Together, these actions of NE may contribute to the headache
      phase of migraine.

PMID- 25601918
TI  - Images in Vascular Medicine. Infrarenal inferior vena cava injury after blunt
      trauma.

PMID- 25601917
TI  - Postoperative prophylaxis of venous thromboembolism (VTE) in patients undergoing
      high ligation and stripping of the great saphenous vein (GSV).
AB  - To analyze the necessity of venous thromboembolism (VTE) prophylaxis for patients
      undergoing high ligation and stripping of the great saphenous vein (GSV) and to
      estimate the efficacy and safety of different anticoagulant protocols in a single
      center randomized controlled trial with large sample size. A total of 2196
      patients undergoing high ligation and stripping of the GSV were randomized to one
      of the following postoperative VTE prophylaxis protocols: group A, no VTE
      prophylaxis (n=542); group B, subcutaneous low-dose unfractionated heparin (LDUH)
      hypodermic injection, 125 U/kg per day in three divided doses (n=531); group C,
      low-molecular-weight heparin (LMWH) 6000 IU once a day (n=573); and group D, LMWH
      4000 IU twice daily (n=550). Groups were compared for the incidence of VTE and
      major hemorrhage within 1 month following surgery. Varicose vein severity was
      classified by CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic elements)
      score. The clinical characteristics of the patients were equally matched between
      groups. Postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) were
      significantly higher in group A (DVT 5.17%, PE 1.48%) compared to groups B
      (0.56%, 0%), C (0.35%, 0%) and D (0.36%, 0%) (p<0.01). The incidence of VTE did
      not differ between the three active chemoprophylaxis arms. Hemorrhagic
      complications were low for each group but higher in group B (0.75%) compared to
      the other groups (group A 0.18%; group C 0.17%; group D 0.18%, p<0.01).
      Hemorrhagic complications did not differ amongst groups A, C and D. In
      conclusion, postoperative VTE chemoprophylaxis following high ligation and GSV
      stripping effectively reduces the venous thrombosis complications of this
      procedure. Of the three active strategies tested, no difference in efficacy was
      noted; however, thrice daily LDUH did increase bleeding complications. 

PMID- 25601919
TI  - Physiopathology of dementia from the perspective of traditional Persian medicine.
AB  - The most common cognitive disorder that is disabling is dementia. During the
      medieval period, traditional Persian medicine was an outstanding source of
      medicine that was used as standard references in medical schools of in the West
      and Middle East. In ancient manuscripts of traditional Persian medicine, a
      condition has been introduced similar to dementi (raoonat and homgh). In this
      article, by collecting materials of traditional medicine texts on dementia, we
      aim to provide theories for further studies on this topics, as there is an
      obvious difference between traditional Persian medicine and modern medicine with
      regard to dementia; however, since modern medicine has not found a suitable
      response to treatment for all diseases, reviewing traditional Persian medicine
      for finding better treatment strategies is wise. Use of all medical potentials
      approved by the World Health Organization beside classic medicine like
      traditional medicine and considering the availability and acceptability among
      people is recommended. 

PMID- 25601921
TI  - Porcine beta-defensin 2 attenuates inflammation and mucosal lesions in dextran
      sodium sulfate-induced colitis.
AB  - Intestinal permeability plays a critical role in the etiopathogenesis of
      ulcerative colitis. Defensins, including porcine beta-defensin (pBD)2, are
      crucial antimicrobial peptides for gut protection owing to their antibacterial
      and immunomodulatory activities. The purpose of this study was to investigate the
      protective effects of pBD2 on mucosal injury and the disruption of the epithelial
      barrier during the pathological process of dextran sodium sulfate (DSS)-induced
      colitis. The effects and mechanism of pBD2 were evaluated both using a DSS
      induced C57BL/6 mouse model and, in vitro, using Caco-2 and RAW264.7 cells. DSS
      induced colitis was characterized by higher disease activity index, shortened
      colon length, elevated activities of myeloperoxidase and eosinophil peroxidase,
      histologic evidence of inflammation, and increased expression levels of TNF
      alpha, IL-6, and IL-8. pBD2 increased the expression of zonula occludens-1,
      zonula occludens-2, claudin-1, mucin-1, and mucin-2 mRNA and proteins, and it
      decreased permeability to FITC-D, as well as apoptosis, in DSS-treated mice. pBD2
      also decreased inflammatory infiltrates of the colon epithelium. In Caco-2 cells,
      pBD2 increased transepithelial electrical resistance and mucin mRNA expression,
      and it decreased the permeability of FITC-D while preserving the structural
      integrity of the tight junctions. The effects of pBD2 appeared to be through
      upregulation of the expression of genes associated with tight junctions and
      mucins, and by suppressing DSS-induced increases in inflammation, inducible NO
      synthase, cyclooxygenase-2, and apoptosis. These results show that pBD2 improves
      DSS-induced changes in mucosal lesions and paracellular permeability, possibly by
      affecting the activation of NF-kappaB signaling. The present study demonstrates
      that intrarectal administration of pBD2 may be a novel preventive option for
      ulcerative colitis. 

PMID- 25601920
TI  - Unique ligand-binding property of the human IgM Fc receptor.
AB  - The IgM Fc receptor (FcMUR) is the newest FcR, and coligation of FcMUR and
      Fas/CD95 on Jurkat cells with agonistic IgM anti-Fas mAb was shown to inhibit Fas
      induced apoptosis. The ligand-binding activity of human FcMUR was further
      examined. FcMUR-mediated protection from apoptosis was partially blocked by
      addition of 10(4) molar excess of IgM or its soluble immune complexes, but it
      could be inhibited by addition of 10-fold excess of IgM anti-CD2 mAb. This
      suggests that FcMUR binds more efficiently to the Fc portion of IgM reactive with
      plasma-membrane proteins than to the Fc portion of IgM in solution. The former
      interaction occurred in cis on the same cell surface, but not in trans between
      neighboring cells. This cis engagement of FcMUR resulted in modulation of Ca(2+)
      mobilization via CD2 on Jurkat cells or BCRs on blood B cells upon cross-linkage
      with the corresponding IgM mAbs. Several functional changes were observed with
      FcMUR mutants: 1) significant increase in IgM ligand binding in the cytoplasmic
      tail-deletion mutant, 2) enhanced cap formation in FcMUR upon IgM binding at 4
      degrees C with a point mutation of the transmembrane His to Phe, and 3) less
      protective activity of FcMUR in IgM anti-Fas mAb-mediated apoptosis assays with a
      point mutation of the membrane-proximal Tyr to Phe. These findings show the
      importance of the cis engagement of FcMUR and its critical role in receptor
      function. Hence, FcMUR on B, T, and NK cells may modulate the function of surface
      proteins recognized by natural or immune IgM Abs on the shared membrane cell
      surface. 

PMID- 25601922
TI  - Transplanted bone marrow-derived circulating PDGFRalpha+ cells restore type VII
      collagen in recessive dystrophic epidermolysis bullosa mouse skin graft.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is an intractable genetic
      blistering skin disease in which the epithelial structure easily separates from
      the underlying dermis because of genetic loss of functional type VII collagen
      (Col7) in the cutaneous basement membrane zone. Recent studies have demonstrated
      that allogeneic bone marrow transplantation (BMT) ameliorates the skin blistering
      phenotype of RDEB patients by restoring Col7. However, the exact therapeutic
      mechanism of BMT in RDEB remains unclear. In this study, we investigated the
      roles of transplanted bone marrow-derived circulating mesenchymal cells in RDEB
      (Col7-null) mice. In wild-type mice with prior GFP-BMT after lethal irradiation,
      lineage-negative/GFP-positive (Lin(-)/GFP(+)) cells, including platelet-derived
      growth factor receptor alpha-positive (PDGFRalpha(+)) mesenchymal cells,
      specifically migrated to skin grafts from RDEB mice and expressed Col7. Vascular
      endothelial cells and follicular keratinocytes in the deep dermis of the skin
      grafts expressed SDF-1alpha, and the bone marrow-derived PDGFRalpha(+) cells
      expressed CXCR4 on their surface. Systemic administration of the CXCR4 antagonist
      AMD3100 markedly decreased the migration of bone marrow-derived PDGFRalpha(+)
      cells into the skin graft, resulting in persistent epidermal detachment with
      massive necrosis and inflammation in the skin graft of RDEB mice; without AMD3100
      administration, Col7 was significantly supplemented to ameliorate the pathogenic
      blistering phenotype. Collectively, these data suggest that the SDF1alpha/CXCR4
      signaling axis induces transplanted bone marrow-derived circulating PDGFRalpha(+)
      mesenchymal cells to migrate and supply functional Col7 to regenerate RDEB skin. 

PMID- 25601923
TI  - Engulfment of activated apoptotic cells abolishes TGF-beta-mediated
      immunoregulation via the induction of IL-6.
AB  - Phagocytosis of apoptotic cells (ACs) is usually a potent immunoregulatory signal
      but can also promote inflammation. In this article, we show that administration
      of apoptotic dendritic cells (DCs) inhibited inflammation in vivo through
      increasing production of TGF-beta from intrinsic DCs and B cells. However, ACs
      derived from LPS-activated DCs failed to restrain inflammation because of a short
      lived but marked IL-6 response, which abolished the increase in TGF-beta.
      Inhibition of IL-6 restored the protective anti-inflammatory properties of aACs
      and the TGF-beta response. DCs isolated from mice that had received resting but
      not activated ACs could transfer the suppression of inflammation to recipient
      mice. These transferred DCs stimulated B cell TGF-beta production and relied on
      an intact B cell compartment to limit inflammation. These results highlight how
      the activation state of AC governs their ability to control inflammation through
      reciprocal regulation of IL-6 and TGF-beta. 

PMID- 25601924
TI  - Cutting Edge: DNase II deficiency prevents activation of autoreactive B cells by
      double-stranded DNA endogenous ligands.
AB  - In mice that fail to express the phagolysosomal endonuclease DNase II and the
      type I IFN receptor, excessive accrual of undegraded DNA results in a STING
      dependent, TLR-independent inflammatory arthritis. These double-knockout (DKO)
      mice develop additional indications of systemic autoimmunity, including anti
      nuclear autoantibodies and splenomegaly, that are not found in Unc93b1(3d/3d) DKO
      mice and, therefore, are TLR dependent. The DKO autoantibodies predominantly
      detect RNA-associated autoantigens, which are commonly targeted in TLR7-dominated
      systemic erythematosus lupus-prone mice. To determine whether an inability of
      TLR9 to detect endogenous DNA could explain the absence of dsDNA-reactive
      autoantibodies in DKO mice, we used a novel class of bifunctional autoantibodies,
      IgM/DNA dual variable domain Ig molecules, to activate B cells through a BCR/TLR9
      dependent mechanism. DKO B cells could not respond to the IgM/DNA dual variable
      domain Ig molecule, despite a normal response to both anti-IgM and CpG ODN 1826.
      Thus, DKO B cells only respond to RNA-associated ligands because DNase II
      mediated degradation of self-DNA is required for TLR9 activation. 

PMID- 25601925
TI  - A nonhuman primate scrub typhus model: protective immune responses induced by
      pKarp47 DNA vaccination in cynomolgus macaques.
AB  - We developed an intradermal (ID) challenge cynomolgus macaque (Macaca
      fascicularis) model of scrub typhus, the leading cause of treatable
      undifferentiated febrile illness in tropical Asia, caused by the obligate
      intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal
      model is required for the development of clinically relevant diagnostic assays
      and evaluation of therapeutic agents and candidate vaccines. We investigated
      scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa,
      Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus
      vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle)
      for safety, immunogenicity, and efficacy against homologous ID challenge with O.
      tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars,
      lymphadenopathy, bacteremia, altered liver function, increased WBC counts,
      pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses.
      Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly
      increased O. tsutsugamushi-specific, IFN-gamma-producing PBMCs (p = 0.04),
      reduced eschar frequency and bacteremia duration (p <= 0.01), delayed bacteremia
      onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater
      reduction of liver transaminase levels (p < 0.03) than controls. This study
      demonstrates a vaccine-induced immune response capable of conferring sterile
      immunity against high-dose homologous ID challenge of O. tsutsugamushi in a
      nonhuman primate model, and it provides insight into cell-mediated immune control
      of O. tsutsugamushi and dissemination dynamics, highlights the importance of
      bacteremia indices for evaluation of both natural and vaccine-induced immune
      responses, and importantly, to our knowledge, has determined the first phenotypic
      correlates of immune protection in scrub typhus. We conclude that this model is
      suitable for detailed investigations into vaccine-induced immune responses and
      correlates of immunity for scrub typhus. 

PMID- 25601926
TI  - JNK regulatory molecule G5PR induces IgG autoantibody-producing plasmablasts from
      peritoneal B1a cells.
AB  - Peritoneal B1a cells expressing CD5 and CD11b generate autoantibody-producing
      precursors in autoimmune-prone mice. Previous studies show reduced JNK signaling
      in peritoneal B1a cells of female New Zealand Black mice and an abnormal increase
      of protein phosphatase 2A subunit G5PR that regulates BCR-mediated JNK signaling
      as a cause of autoimmunity. To investigate the mechanism regulating B1a
      differentiation into autoantibody-secreting plasmablasts (PBs), we applied an in
      vitro culture system that supports long-term growth of germinal center (GC) B
      cells (iGB) with IL-4, CD40L, and BAFF. Compared with spleen B2 cells, B1a cells
      differentiated into GC-like B cells, but more markedly into PBs, and underwent
      class switching toward IgG1. During iGB culture, B1a cells expressed GC
      associated aicda, g5pr, and bcl6, and markedly PB-associated prdm1, irf4, and
      xbp1. B1a-derived iGB cells from New Zealand Black * New Zealand White F1 mice
      highly differentiated into autoantibody-secreting PBs in vitro and localized to
      the GC area in vivo. In iGB culture, JNK inhibitor SP600125 augmented the
      differentiation of C57BL/6 B1a cells into PBs. Furthermore, B1a cells from G5PR
      transgenic mice markedly differentiated into IgM and IgG autoantibody-secreting
      PBs. In conclusion, JNK regulation is critical to suppress autoantibody-secreting
      PBs from peritoneal B1a cells. 

PMID- 25601927
TI  - miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory
      cells.
AB  - Micro-RNAs (miRNAs) are small noncoding RNAs that regulate various biological
      pathways. As their role in phagocytosis remains poorly understood, we
      investigated their impact on phagocytosis in myeloid inflammatory cells. Seven
      miRNAs (miR-24, -30b, -101, 142-3p, -652-3p, -652-5p, and -1275) that were
      differentially expressed during monocyte to macrophage (Mphi) and monocyte to
      dendritic cell (DC) differentiation were screened for their potential role in
      phagocytosis. Among these, overexpression of miR-24, miR-30b, and miR-142-3p in
      human monocyte-derived Mphi, DC, monocytes, and PBMCs significantly attenuate
      phagocytosis of Escherichia coli and Staphylococcus aureus, as well as the
      secretion of inflammatory mediators, including TNF-alpha, IL-6, and IL-12p40.
      miRNA-mediated changes in cytokine profiles were observed at transcriptional
      and/or posttranscriptional levels and importantly exhibit miRNA-specific impact.
      To examine the underlying mechanism, we monitored the expression of phagocytosis
      pathway-associated genes and identified several genes that were altered in Mphi
      and DC transfected with miR-24, miR-30b, and miR-142-3p mimics. Some of these
      genes with altered expression also harbor putative miRNA binding sites. We show
      that miR-142-3p directly regulates protein kinase Calpha (PKCalpha), a key gene
      involved in phagocytosis. Interestingly, miR-142-3p and PKCalpha exhibit
      antagonistic expression during Mphi and DC differentiation. Short interfering RNA
      mediated knockdown of PKCalpha in Mphi leads to reduced bacterial uptake, further
      highlighting the role of the gene in phagocytosis. Overall, these results
      demonstrate that miR-24, miR-30b, and miR-142-3p regulate phagocytosis and
      associated cytokine production in myeloid inflammatory cells through modulation
      of various genes involved in the pathway. 

PMID- 25601928
TI  - In vivo 4-1BB deficiency in myeloid cells enhances peripheral T cell
      proliferation by increasing IL-15.
AB  - 4-1BB signals are considered positive regulators of T cell responses against
      viruses and tumors, but recent studies suggest that they have more complex roles
      in modulating T cell responses. Although dual roles of 4-1BB signaling in T cell
      responses have been suggested, the underlying mechanisms are still not fully
      understood. In this study, we tested whether 4-1BB expression affected T cell
      responses differently when expressed in myeloid versus lymphoid cells in vivo. By
      assessing the proliferation of 4-1BB(+/+) and 4-1BB(-/-) T cells in lymphocyte
      deficient RAG2(-/-) and RAG2(-/-)4-1BB(-/-) mice, we were able to compare the
      effects on T cell responses of 4-1BB expression on myeloid versus T cells.
      Surprisingly, adoptively transferred T cells were more responsive in tumor
      bearing RAG2(-/-)4-1BB(-/-) mice than in RAG2(-/-) mice, and this enhanced T cell
      proliferation was further enhanced if the T cells were 4-1BB deficient. Dendritic
      cells (DCs) rather than NK or tissue cells were the myeloid lineage cells
      primarily responsible for the enhanced T cell proliferation. However, individual
      4-1BB(-/-) DCs were less effective in T cell priming in vivo than 4-1BB(+/+) DCs;
      instead, more DCs in the secondary lymphoid organs of RAG2(-/-)4-1BB(-/-) mice
      appeared to induce the enhanced T cell proliferation by producing and
      transpresenting more IL-15. Therefore, we conclude that in vivo 4-1BB signaling
      of myeloid cells negatively regulates peripheral T cell responses by limiting the
      differentiation of DCs and their accumulation in secondary lymphoid organs. 

PMID- 25601929
TI  - Combined effect of blood pressure and total cholesterol levels on long-term risks
      of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from
      Observational Cohorts in Japan.
AB  - No large-scale, longitudinal studies have examined the combined effects of blood
      pressure (BP) and total cholesterol levels on long-term risks for subtypes of
      cardiovascular death in an Asian population. To investigate these relationships,
      a meta-analysis of individual participant data, which included 73 916 Japanese
      subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a
      mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic
      stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases,
      respectively. Cohort-stratified Cox proportional hazard models were used. After
      stratifying the participants by 4 systolic BP *4 total cholesterol categories,
      the group with systolic BP >=160 mm Hg with total cholesterol >=5.7 mmol/L had
      the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39;
      P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7
      mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with
      increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group
      with total cholesterol >=5.7 mmol/L). Similarly, the adjusted hazard ratios of
      total cholesterol increased with increases in systolic BP categories (P for
      interaction <=0.04). Systolic BP was positively associated with ischemic stroke
      and intraparenchymal hemorrhage death, and total cholesterol was inversely
      associated with intraparenchymal hemorrhage, but no significant interactions
      between BP and total cholesterol were observed for stroke. High BP and high total
      cholesterol can synergistically increase the risk for coronary heart disease
      death but not for stroke in the Asian population. 

PMID- 25601930
TI  - Ambulatory blood pressure and its variability in adults born preterm.
AB  - Adults born preterm have higher blood pressure (BP) than those born at term. Most
      studies have focused on preterm birth, and few have assessed BP variability, an
      independent risk factor of cardiovascular disease. We studied the association of
      preterm birth with 24-hour ambulatory BP, measured by an oscillometric device, in
      42 young adults born early preterm (<34 weeks), 72 born late preterm (34-36
      weeks), and 103 controls (>=37 weeks). Sleep was confirmed with accelerometry in
      72.4% of subjects. The 24-hour systolic BP of adults born early preterm was 5.5
      mm Hg higher (95% confidence interval, 1.9-9.3), awake systolic BP was 6.4 mm Hg
      higher (95% confidence interval, 2.8-10.1), and sleeping systolic BP was 2.9 mm
      Hg higher (95% confidence interval 0.3-7.5) when adjusted for age, sex, and use
      of accelerometry. The differences remained similar when adjusted for height, body
      mass index, physical activity, smoking, parental education, maternal body mass
      index, smoking during pregnancy, and gestational diabetes mellitus and attenuated
      slightly when adjusted for maternal hypertensive pregnancy disorders. Adults born
      early preterm also had higher BP variability as indicated by higher individual
      standard deviations of systolic BP and diastolic BP. Although our results were
      consistent with a dose-response relationship between shorter gestation and higher
      BP, the difference between the late preterm and term groups was not statistically
      significant. Our results suggest that the higher BP in adults born early preterm
      is present during both waking and sleeping hours, may be more pronounced during
      waking hours, and is accompanied by higher individual BP variability. 

PMID- 25601931
TI  - Foxp3+ regulatory T cells play a protective role in angiotensin II-induced aortic
      aneurysm formation in mice.
AB  - Although regulatory T cells (Tregs) have been shown to play a protective role in
      abdominal aortic aneurysm (AAA) formation, it remains unclear whether expansion
      of endogenous Foxp3(+) Tregs prevents AAA. In the current study, we determined
      the effects of endogenous Foxp3(+) Treg expansion or depletion in an experimental
      model of AAA. We continuously infused 12-week-old apolipoprotein E-deficient mice
      fed a high-cholesterol diet with angiotensin II (n=60) or normal saline (n=12) by
      implanting osmotic mini-pumps and evaluated AAA formation at 16 weeks. The
      angiotensin II-infused mice received interleukin-2/anti-interleukin-2 monoclonal
      antibody complex (interleukin-2 complex; n=31) or PBS (n=29). Eighty-one percent
      of angiotensin II-infused mice developed AAA, with 42% mortality possibly because
      of aneurysm rupture. Interleukin-2 complex treatment systemically increased the
      number of Foxp3(+) Tregs and significantly decreased the incidence (52%) and
      mortality (17%) of AAA. Immunohistochemical analysis showed reduced accumulation
      of macrophages and increased numbers of Foxp3(+) Tregs in aneurysmal tissues,
      suggesting that expansion of Tregs may suppress local inflammation in the vessel
      wall and provide protection against AAA formation. Furthermore, genetic depletion
      of Foxp3(+) Tregs led to a significant increase in the mortality of AAA,
      suggesting the protective role of Foxp3(+) Tregs against AAA. Our findings
      suggest that Foxp3(+) Tregs may play a protective role in AAA formation and that
      promotion of an endogenous regulatory immune response may be a potentially
      valuable therapeutic approach for preventing AAA. 

PMID- 25601933
TI  - Effects of continuous positive airway pressure treatment on clinic and ambulatory
      blood pressures in patients with obstructive sleep apnea and resistant
      hypertension: a randomized controlled trial.
AB  - The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs)
      in patients with resistant hypertension and obstructive sleep apnea is not
      established. We aimed to evaluate it in a randomized controlled clinical trial,
      with blinded assessment of outcomes. Four hundred thirty-four resistant
      hypertensive patients were screened and 117 patients with moderate/severe
      obstructive sleep apnea, defined by an apnea-hypopnea index >=15 per hour, were
      randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients),
      while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs
      were obtained before and after 6-month treatment. Primary outcomes were changes
      in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to
      treat and per-protocol (limited to those with uncontrolled ambulatory BPs)
      analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm
      Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea-hypopnea index was 41 per
      hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat
      analysis, there was no significant difference in any BP change, neither in
      nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was
      on night-time systolic blood pressure in per-protocol analysis, with greater
      reduction of 4.7 mm Hg (95% confidence interval, -11.3 to +3.1 mm Hg; P=0.24) and
      an increase in nocturnal BP fall of 2.2% (95% confidence interval, -1.6% to
      +5.8%; P=0.25), in comparison with control group. In conclusion, CPAP treatment
      had no significant effect on clinic and ambulatory BPs in patients with resistant
      hypertension and moderate/severe obstructive sleep apnea, although a beneficial
      effect on night-time systolic blood pressure and on nocturnal BP fall might exist
      in patients with uncontrolled ambulatory BP levels.

PMID- 25601934
TI  - Renin, genes, microRNAs, and renal mechanisms involved in hypertension.

PMID- 25601932
TI  - Renal transporter activation during angiotensin-II hypertension is blunted in
      interferon-gamma-/- and interleukin-17A-/- mice.
AB  - Ample genetic and physiological evidence establishes that renal salt handling is
      a critical regulator of blood pressure. Studies also establish a role for the
      immune system, T-cell infiltration, and immune cytokines in hypertension. This
      study aimed to connect immune cytokines, specifically interferon-gamma (IFN
      gamma) and interleukin-17A (IL-17A), to sodium transporter regulation in the
      kidney during angiotensin-II (Ang-II) hypertension. C57BL/6J (wild-type) mice
      responded to Ang-II infusion (490 ng/kg per minute, 2 weeks) with a rise in blood
      pressure (170 mm Hg) and a significant decrease in the rate of excretion of a
      saline challenge. In comparison, mice that lacked the ability to produce either
      IFN-gamma (IFN-gamma(-/-)) or IL-17A (IL-17A(-/-)) exhibited a blunted rise in
      blood pressure (<150 mm Hg), and both the genotypes maintained baseline diuretic
      and natriuretic responses to a saline challenge. Along the distal nephron, Ang-II
      infusion increased abundance of the phosphorylated forms of the Na-K-2Cl
      cotransporter, Na-Cl cotransporter, and Ste20/SPS-1-related proline-alanine-rich
      kinase, in both the wild-type and the IL-17A(-/-) but not in IFN-gamma(-/-) mice;
      epithelial Na channel abundance increased similarly in all the 3 genotypes. In
      the proximal nephron, Ang-II infusion significantly decreased abundance of Na/H
      exchanger isoform 3 and the motor myosin VI in IL-17A(-/-) and IFN-gamma(-/-),
      but not in wild-type; the Na-phosphate cotransporter decreased in all the 3
      genotypes. Our results suggest that during Ang-II hypertension both IFN-gamma and
      IL-17A production interfere with the pressure natriuretic decrease in proximal
      tubule sodium transport and that IFN-gamma production is necessary to activate
      distal sodium reabsorption. 

PMID- 25601935
TI  - Science on a Shoestring: Building Nursing Knowledge With Limited Funding.
AB  - Building the science for nursing practice has never been more important. However,
      shrunken federal and state research budgets mean that investigators must find
      alternative sources of financial support and develop projects that are less
      costly to carry out. New investigators often build beginning programs of research
      with limited funding. This article provides an overview of some cost-effective
      research approaches and gives suggestions for finding other sources of funding.
      Examples of more cost-effective research approaches include adding complementary
      questions to existing funded research projects; conducting primary analysis of
      electronic patient records and social media content; conducting secondary
      analysis of data from completed studies; reviewing and synthesizing previously
      completed research; implementing community-based participatory research;
      participating in collaborative research efforts such as inter-campus team
      research, practice-based research networks (PBRNs), and involving undergraduate
      and doctoral students in research efforts. Instead of relying on funding from the
      National Institutes of Health (NIH) and other government agencies, nurse
      researchers may be able to find support for research from local sources such as
      businesses, organizations, or clinical agencies. Investigators will increasingly
      have to rely on these and other creative approaches to fund and implement their
      research programs if granting agency budgets do not significantly expand. 

PMID- 25601936
TI  - Evaluation of a BCMA's Electronic Medication Administration Record.
AB  - Barcode medication administration (BCMA) systems can reduce medication errors,
      but sociotechnical issues are quite common. Although crucial to nurses' work, few
      usability evaluations are available for electronic medication administration
      record (eMARs) screens. The purpose of this research was to identify current
      usability problems in the Veterans Administration's (VA) eMAR/BCMA system and
      explore how these might affect nurses' situation awareness (SA). Three expert
      evaluators used 10 tasks/elements, heuristic evaluation techniques, and explored
      potential impacts using a SA perspective. The results yielded 99 usability
      problems categorized into 440 heuristic violations with the largest volume in the
      category of Match With the Real World. Fifteen usability issues were rated as
      catastrophic with the Administer/Chart medications task having the most.
      Situational awareness was affected at all levels, especially at Level 2,
      Comprehension. Usability problems point to important areas for improvement,
      because these issues have the potential to affect nurses' SA, "at a glance"
      information, nurse productivity, and patient safety. 

PMID- 25601937
TI  - The association of the rapid assessment of supervision scale score and
      unintentional childhood injury.
AB  - Supervisory neglect is often considered in medical settings when a child presents
      with an unintentional injury. The Rapid Assessment of Supervision Scale (RASS) is
      a clinical decision-making tool for the assessment of supervision of young
      children. As the next step in the development of the RASS, we assessed the
      association of RASS scores with unintentional injury. This study was a secondary
      analysis of data from a case-crossover study, which examined the association of
      parental supervision and unintentional injury in children. Data on supervision
      characteristics for 3 time periods for each child were available, that is, one
      injury scenario and two "control" time periods when no injury occurred. Blinded
      to injury status, four raters independently evaluated adequacy of supervision in
      132 supervision scenarios using the RASS. The individual RASS scores of the four
      raters and the group (mean) RASS score of the four raters were evaluated for
      associations with injury status. Individual scores from three of the four raters
      demonstrated significant associations of increasing RASS scores with injury.
      Increasing group RASS scores (odds ratio = 2.8; 95% confidence interval [1.5,
      5.1]) were associated with greater likelihood of injury. Further testing may
      result in a tool that aids medical personnel in the evaluation of adequacy of
      supervision. 

PMID- 25601938
TI  - Commentary on the Report of the APSAC Task Force on evidence-based service
      planning guidelines for child welfare.

PMID- 25601939
TI  - A comparison of self-reported emotional and trauma-related concerns among
      sexually abused children with and without sexual behavior problems.
AB  - Numerous studies document concomitant features of sexual behavior problems (SBPs)
      among children 12 years of age or younger, but rarely does research involve child
      self-report assessments. This study provides the most comprehensive examination
      to date of self-reported concerns among children with SBP, using a large sample
      (N = 392) of clinically referred participants who reported sexual abuse
      histories. Children between the ages of 8 and 12 were categorized as
      demonstrating SBP (n = 203) or not demonstrating SBP (n = 189) as determined by
      scores on the Child Sexual Behavior Inventory. Children completed the Trauma
      Symptom Checklist for Children, and caregivers completed the Child Behavior
      Checklist. Self-reports of children showed that those with SBP reported
      significantly greater concerns in all areas, including sexual preoccupation and
      sexual distress, than their peers not demonstrating SBP. Caregivers of children
      in the SBP group reported greater concerns of internalizing and externalizing
      problems than the caregivers of children who did not have SBP. Implications for
      clinical practice and future research are discussed. Specifically, it is
      recommended that future research improve on the manner in which sexual abuse and
      SBPs were defined and assessed. 

PMID- 25601940
TI  - Genomic epidemiology of multidrug-resistant Mycobacterium tuberculosis during
      transcontinental spread.
AB  - The transcontinental spread of multidrug-resistant (MDR) tuberculosis is poorly
      characterized in molecular epidemiologic studies. We used genomic sequencing to
      understand the establishment and dispersion of MDR Mycobacterium tuberculosis
      within a group of immigrants to the United States. We used a genomic epidemiology
      approach to study a genotypically matched (by spoligotype, IS6110 restriction
      fragment length polymorphism, and mycobacterial interspersed repetitive units
      variable number of tandem repeat signature) lineage 2/Beijing MDR strain
      implicated in an outbreak of tuberculosis among refugees in Thailand and
      consecutive cases within California. All 46 MDR M. tuberculosis genomes from both
      Thailand and California were highly related, with a median difference of 10
      single-nucleotide polymorphisms (SNPs). The Wat Tham Krabok (WTK) strain is a new
      sequence type distinguished from all known Beijing strains by 55 SNPs and a
      genomic deletion (Rv1267c) associated with increased fitness. Sequence data
      revealed a highly prevalent MDR strain that included several closely related but
      distinct allelic variants within Thailand, rather than the occurrence of a single
      outbreak. In California, sequencing data supported multiple independent
      introductions of WTK with subsequent transmission and reactivation within the
      state, as well as a potential super spreader with a prolonged infectious period.
      Twenty-seven drug resistance-conferring mutations and 4 putative compensatory
      mutations were found within WTK strains. Genomic sequencing has substantial
      epidemiologic value in both low- and high-burden settings in understanding
      transmission chains of highly prevalent MDR strains. 

PMID- 25601943
TI  - Model inadequacy and mistaken inferences of trait-dependent speciation.
AB  - Species richness varies widely across the tree of life, and there is great
      interest in identifying ecological, geographic, and other factors that affect
      rates of species proliferation. Recent methods for explicitly modeling the
      relationships among character states, speciation rates, and extinction rates on
      phylogenetic trees- BiSSE, QuaSSE, GeoSSE, and related models-have been widely
      used to test hypotheses about character state-dependent diversification rates.
      Here, we document the disconcerting ease with which neutral traits are inferred
      to have statistically significant associations with speciation rate. We first
      demonstrate this unfortunate effect for a known model assumption violation:
      shifts in speciation rate associated with a character not included in the model.
      We further show that for many empirical phylogenies, characters simulated in the
      absence of state-dependent diversification exhibit an even higher Type I error
      rate, indicating that the method is susceptible to additional, unknown model
      inadequacies. For traits that evolve slowly, the root cause appears to be a
      statistical framework that does not require replicated shifts in character state
      and diversification. However, spurious associations between character state and
      speciation rate arise even for traits that lack phylogenetic signal, suggesting
      that phylogenetic pseudoreplication alone cannot fully explain the problem. The
      surprising severity of this phenomenon suggests that many trait-diversification
      relationships reported in the literature may not be real. More generally, we
      highlight the need for diagnosing and understanding the consequences of model
      inadequacy in phylogenetic comparative methods. 

PMID- 25601942
TI  - A Japanese Encephalitis Vaccine From India Induces Durable and Cross-protective
      Immunity Against Temporally and Spatially Wide-ranging Global Field Strains.
AB  - BACKGROUND: Japanese encephalitis (JE) is a vaccine-preventable acute disease. We
      report the results of a phase 2/3 trial of JENVAC, a Vero cell-derived vaccine
      developed using an Indian strain of JE virus (JEV). METHODS: JENVAC was
      administered in 2 doses 28 days apart, and immunogenicity was compared to that
      from a single dose of SA-14-14-2, the only approved JE vaccine and regimen at the
      time in India. RESULTS: After both the doses, seroconversion and seroprotection
      were >90% for JENVAC. For SA-14-14-2, seroconversion and seroprotection were
      57.69% and 77.56%, respectively, on day 28 and 39.74% and 60.26%, respectively,
      on day 56. The geometric mean titers at day 28 and day 56 were 145.04 and 460.53,
      respectively, for JENVAC and 38.56 and 25.29, respectively, for SA-14-14-2. With
      a single dose of JENVAC, seroprotection titers lasted at least 12 months in >80%
      of the subjects. Following receipt of 2 doses, 61.17% of subjects retained
      seroprotection titers at 24 months, and immunogenicity criteria were higher than
      that for SA-14-14-2 at 12, 18, and 24 months each. Sera from JENVAC subjects
      neutralized JEV genotypes I, II, III, and IV equally well. Adverse events were
      not significantly different between the 2 vaccines. CONCLUSIONS: JENVAC elicits
      long-lasting, broadly protective immunity. CLINICAL TRIALS REGISTRATION:
      CTRI/2011/07/001855.

PMID- 25601945
TI  - Anxiety and depression among amyloid light-chain cardiac amyloidosis patients:
      The role of life satisfaction.
AB  - BACKGROUND: The present study aimed to provide a contribution to the study of a
      rare disease, amyloid light-chain (AL) cardiac amyloidosis, which is the most
      common type of systemic amyloidosis. In AL amyloidosis prognosis is determined by
      cardiac involvement. Although the association between psychological distress
      (e.g. anxiety and depression) and AL cardiac amyloidosis is documented, very
      little is known about the psychosocial variables that may mediate the
      association. AIMS: The aim of the study is therefore to examine the potential
      mediating role of life satisfaction in the relationship between cardiac symptom
      severity (independent variable) and anxious and depressive symptoms (dependent
      variables) in AL patients. METHOD: Forty-three AL amyloidosis patients (57.1%
      males) with cardiac amyloidosis were administered the Satisfaction with Life
      Scale, the State-Trait Anxiety Inventory and the Centre for Epidemiological Study
      Depression Scale. Clinical variables such as months since cardiac symptom onset
      and cardiac symptom severity were collected. RESULTS: Findings showed significant
      relationships between symptom severity and psychological disorders (e.g. anxiety
      and depression) and these were mediated by life satisfaction. CONCLUSION:
      Overall, findings highlight the importance of subjective well-being (e.g. life
      satisfaction) to reduce anxious and depressive symptoms and to improve general
      health in AL patients.

PMID- 25601944
TI  - Delimiting Species-Poor Data Sets using Single Molecular Markers: A Study of
      Barcode Gaps, Haplowebs and GMYC.
AB  - Most single-locus molecular approaches to species delimitation available to date
      have been designed and tested on data sets comprising at least tens of species,
      whereas the opposite case (species-poor data sets for which the hypothesis that
      all individuals are conspecific cannot by rejected beforehand) has rarely been
      the focus of such attempts. Here we compare the performance of barcode gap
      detection, haplowebs and generalized mixed Yule-coalescent (GMYC) models to
      delineate chimpanzees and bonobos using nuclear sequence markers, then apply
      these single-locus species delimitation methods to data sets of one, three, or
      six species simulated under a wide range of population sizes, speciation rates,
      mutation rates and sampling efforts. Our results show that barcode gap detection
      and GMYC models are unable to delineate species properly in data sets composed of
      one or two species, two situations in which haplowebs outperform them. For data
      sets composed of three or six species, bGMYC and haplowebs outperform the single
      threshold and multiple-threshold versions of GMYC, whereas a clear barcode gap is
      only observed when population sizes and speciation rates are both small. The
      latter conditions represent a "sweet spot" for molecular taxonomy where all the
      single-locus approaches tested work well; however, the performance of these
      methods decreases strongly when population sizes and speciation rates are high,
      suggesting that multilocus approaches may be necessary to tackle such cases. 

PMID- 25601946
TI  - Helicoverpa zea (Lepidoptera: Noctuidae) and Spodoptera frugiperda (Lepidoptera:
      Noctuidae) Responses to Sorghum bicolor (Poales: Poaceae) Tissues From Lowered
      Lignin Lines.
AB  - The presence of lignin within biomass impedes the production of liquid fuels.
      Plants with altered lignin content and composition are more amenable to
      lignocellulosic conversion to ethanol and other biofuels but may be more
      susceptible to insect damage where lignin is an important resistance factor.
      However, reduced lignin lines of switchgrasses still retained insect resistance
      in prior studies. Therefore, we hypothesized that sorghum lines with lowered
      lignin content will also retain insect resistance. Sorghum excised leaves and
      stalk pith Sorghum bicolor (L.) Moench (Poales: Poaceae) from near isogenic brown
      midrib (bmr) 6 and 12 mutants lines, which have lowered lignin content and
      increased lignocellulosic ethanol conversion efficiency, were examined for insect
      resistance relative to wild-type (normal BTx623). Greenhouse and growth chamber
      grown plant tissues were fed to first-instar larvae of corn earworms, Helicoverpa
      zea (Boddie) and fall armyworms Spodoptera frugiperda (J.E. Smith) (Lepidoptera:
      Noctuidae), two sorghum major pests. Younger bmr leaves had significantly greater
      feeding damage in some assays than wild-type leaves, but older bmr6 leaves
      generally had significantly less damage than wild-type leaves. Caterpillars
      feeding on the bmr6 leaves often weighed significantly less than those feeding on
      wild-type leaves, especially in the S. frugiperda assays. Larvae fed the pith
      from bmr stalks had significantly higher mortality compared with those larvae fed
      on wild-type pith, which suggested that bmr pith was more toxic. Thus, reducing
      lignin content or changing subunit composition of bioenergy grasses does not
      necessarily increase their susceptibility to insects and may result in increased
      resistance, which would contribute to sustainable production. 

PMID- 25601947
TI  - Quality assessment and improvement of nationwide cancer registration system in
      Taiwan: a review.
AB  - Cancer registration provides core information for cancer surveillance and
      control. The population-based Taiwan Cancer Registry was implemented in 1979.
      After the Cancer Control Act was promulgated in 2003, the completeness (97%) and
      data quality of cancer registry database has achieved at an excellent level.
      Hospitals with 50 or more beds, which provide outpatient and hospitalized cancer
      care, are recruited to report 20 items of information on all newly diagnosed
      cancers to the central registry office (called short-form database). The Taiwan
      Cancer Registry is organized and funded by the Ministry of Health and Welfare.
      The National Taiwan University has been contracted to operate the registry and
      organized an advisory board to standardize definitions of terminology, coding and
      procedures of the registry's reporting system since 1996. To monitor the cancer
      care patterns and evaluate the cancer treatment outcomes, central cancer registry
      has been reformed since 2002 to include detail items of the stage at diagnosis
      and the first course of treatment (called long-form database). There are 80
      hospitals, which count for >90% of total cancer cases, involved in the long-form
      registration. The Taiwan Cancer Registry has run smoothly for >30 years, which
      provides essential foundation for academic research and cancer control policy in
      Taiwan. 

PMID- 25601948
TI  - Using "big data" to dissect clinical heterogeneity.

PMID- 25601949
TI  - A new phenotypic lexicon for accelerated translation: rise of the machines.

PMID- 25601941
TI  - Diminished impact of ethnicity as a risk factor for chronic kidney disease in the
      current HIV treatment era.
AB  - BACKGROUND: Chronic kidney disease (CKD) is an important comorbidity during human
      immunodeficiency virus (HIV) infection. Historically, HIV-associated nephropathy
      has been the predominant cause of CKD and has primarily been observed in people
      of African ancestry. This study aims to investigate the role of ethnicity in
      relation to CKD risk in recent years. METHODS: Analyses were performed including
      16 836 patients from the Dutch AIDS Therapy Evaluation in the Netherlands
      (ATHENA) cohort. Baseline was defined as the first available creatinine level
      measurement after 1 January 2007; CKD was defined as a glomerular filtration rate
      of <60 mL/min/1.73 m(2). The associations between ethnicity and both prevalent
      CKD at baseline and incident CKD during follow-up were analyzed. RESULTS: The
      prevalence of baseline CKD was 2.7% (460 of 16 836 patients). Birth in a sub
      Saharan African country (hereafter, "SSA origin") was significantly associated
      with baseline CKD (adjusted odds ratio 1.49; 95% confidence interval [CI], 1.04
      2.13). During follow-up (median duration, 4.7 years; interquartile range, 2.4
      5.2), the rate of incident CKD was 6.0 events per 1000 person-years. The risk of
      newly developing CKD was similar between patients of SSA origin and those born in
      Western Europe, Australia, or New Zealand (adjusted hazard ratio, 1.00; 95% CI,
      .63-1.59). CONCLUSIONS: Among HIV-infected patients in the Netherlands, being of
      SSA origin was associated with a higher baseline CKD prevalence but had no impact
      on newly developing CKD over time. This suggests a shift in the etiology of CKD
      from HIV-associated nephropathy toward other etiologies.

PMID- 25601950
TI  - Aneurysms of the pulmonary artery.

PMID- 25601951
TI  - Fat embolism syndrome.

PMID- 25601953
TI  - Hypersensitivity reaction in the US Food and Drug Administration-approved second
      generation drug-eluting stents: histopathological assessment with ex vivo optical
      coherence tomography.

PMID- 25601954
TI  - Rare case of cardiac hemangioma causing massive pericardial effusion: can a left
      atrial tumor produce pericardial effusion?

PMID- 25601955
TI  - Letter by Kumar regarding article, "contribution of intimal smooth muscle cells
      to cholesterol accumulation and macrophage-like cells in human atherosclerosis".

PMID- 25601956
TI  - Response to letter regarding article, "contribution of intimal smooth muscle
      cells to cholesterol accumulation and macrophage-like cells in human
      atherosclerosis".

PMID- 25601957
TI  - A Rare Disorder Masquerading as Osteomyelitis. Diagnosis: Multicentric
      Myofibromatosis.

PMID- 25601958
TI  - A Balanced Protocol for Return to School for Children and Youth Following
      Concussive Injury.
AB  - BACKGROUND: Few protocols exist for returning children/youth to school after
      concussion. Childhood concussion can significantly affect school performance,
      which is vital to social development, academic learning, and preparation for
      future roles. The goal of this knowledge translation research was to develop
      evidence based materials to inform physicians about pediatric concussion.
      METHODS: The Return to School (RTS) concussion protocol was developed following
      the National Institute for Health and Care Excellence procedures. RESULTS: Based
      on a scoping review, and stakeholder opinions, an RTS protocol was developed for
      children/youth. This unique protocol focuses on school adaptation in 4 main
      areas: (a) timetable/attendance, (b) curriculum, (c) environmental modifications,
      and (d) activity modifications. CONCLUSION: A balance of cognitive rest and
      timely return to school need to be considered for returning any student to school
      after a concussion. Implementation of these new recommendations may be an
      important tool in prevention of prolonged absence from school and academic
      failure while supporting brain recovery.

PMID- 25601959
TI  - FDA approval: siltuximab for the treatment of patients with multicentric
      Castleman disease.
AB  - On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for
      injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to
      IL6, for the treatment of patients with multicentric Castleman disease (MCD) who
      are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8)
      negative. The approval was primarily based on the results of a randomized, double
      blind trial in which 79 symptomatic patients with MCD were allocated (2:1) to
      siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary
      efficacy endpoint was the proportion of patients in each arm achieving a durable
      tumor and symptomatic response that persisted for a minimum of 18 weeks without
      treatment failure. Tumor response was based on independent review of CT scans
      using the revised Response Criteria for Malignant Lymphoma, and symptomatic
      response was defined as complete resolution or stabilization of 34 MCD-related
      signs and symptoms as reported by the investigator. Thirty-four percent of
      patients in the siltuximab arm and no patients in the placebo arm met the primary
      endpoint (P = 0.0012). The most common adverse reactions (>10% compared with
      placebo) during treatment with siltuximab were pruritus, increased weight, rash,
      hyperuricemia, and upper respiratory tract infection.

PMID- 25601960
TI  - ABCB4 exports phosphatidylcholine in a sphingomyelin-dependent manner.
AB  - ABCB4, which is specifically expressed on the canalicular membrane of
      hepatocytes, exports phosphatidylcholine (PC) into bile. Because SM depletion
      increases cellular PC content and stimulates PC and cholesterol efflux by ABCA1,
      a key transporter involved in generation of HDL, we predicted that SM depletion
      also stimulates PC efflux through ABCB4. To test this prediction, we compared the
      lipid efflux activity of ABCB4 and ABCA1 under SM depletion induced by two
      different types of inhibitors for SM synthesis, myriocin and (1R,3S)-N-(3-hydroxy
      1-hydroxymethyl-3-phenylpropyl)dodecanamide, in human embryonic kidney 293 and
      baby hamster kidney cells. Unexpectedly, SM depletion exerted opposite effects on
      ABCB4 and ABCA1, suppressing PC efflux through ABCB4 while stimulating efflux
      through ABCA1. Both ABCB4 and ABCA1 were recovered from Triton-X-100-soluble
      membranes, but ABCB4 was mainly recovered from CHAPS-insoluble SM-rich membranes,
      whereas ABCA1 was recovered from CHAPS-soluble membranes. These results suggest
      that a SM-rich membrane environment is required for ABCB4 to function. ABCB4 must
      have evolved to exert its maximum activity in the SM-rich membrane environment of
      the canalicular membrane, where it transports PC as the physiological substrate. 

PMID- 25601962
TI  - Breaking down the evidence for bevacizumab in ovarian cancer.

PMID- 25601961
TI  - The implication of cigarette smoking and cessation on macrophage cholesterol
      efflux in coronary artery disease patients.
AB  - We investigated ATP-binding cassette transporters A1/G1 expression and function
      in mediating cholesterol efflux by examining the macrophages of cigarette-smoking
      patients with coronary artery disease (CAD) before and after smoking abstinence.
      Peripheral blood monocyte cells were collected from nonsmokers (n = 17), non-CAD
      (NCAD) smokers (n = 35), and CAD smokers (n = 32) before and after 3 months of
      smoking cessation. We found that the ABCA1 expression level was lower in
      macrophages from NCAD and CAD smokers than from nonsmokers at baseline. The ABCA1
      function of mediating cholesterol efflux was reduced in NCAD and CAD smokers as
      compared with nonsmokers. After 3 months of smoking cessation, ABCA1 expression
      and function were improved in CAD smokers. However, ABCG1 expression and function
      did not change after smoking cessation. Furthermore, ABCA1 expression was
      inhibited by tar in human acute monocytic leukemia cell line THP-1-derived
      macrophages through the inhibition of liver X receptors. Nicotine and carbon
      monoxide did not inhibit ABCA1 expression. Our results indicate that chronic
      cigarette smoking impaired ABCA1-mediated cholesterol efflux in macrophages and
      that tobacco abstinence reversed the function and expression of ABCA1, especially
      in CAD patients. It was tobacco tar, rather than nicotine or carbon monoxide,
      that played a major role in the tobacco-induced disturbance of cellular
      cholesterol homeostasis. 

PMID- 25601963
TI  - A meta-analysis on the impact of platinum-based adjuvant treatment on the outcome
      of borderline ovarian tumors with invasive implants.
AB  - BACKGROUND: Treatment of borderline ovarian tumors (BOTs) remains contentious,
      and there is no consensus regarding therapy for BOTs with invasive implants
      (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in
      patients with BOTi at primary diagnosis. METHODS: The PubMed database was
      systematically searched for articles using the following terms: ((borderline) OR
      (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive
      implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR
      (adjuvant treatment) OR (surgery) OR (surgical treatment)). RESULTS: We
      identified 27 articles including 3,124 patients, 181 with invasive implants. All
      studies provided information regarding mortality or recurrence rates. Central
      pathological examination was performed in 19 studies. Eight studies included more
      than 75% stage I patients; 7 included only advanced-stage patients, and 14
      included only serous BOT. The pooled recurrence estimates for both treatment
      groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ
      significantly (p = .114). A meta-analysis of the 6 studies providing separate
      mortality data for both treatment groups favored surgical treatment only, but
      this difference did not reach statistical significance (.05 < p < .1; odds ratio:
      0.33; 95% confidence interval: 0.09-1.71; p = .086). We were unable to pool the
      results of the included studies because not all studies registered events in both
      treatment groups. Egger's regression indicated low asymmetry of the studies (p =
      .39), and no heterogeneity was found (I(2) = 0%). CONCLUSION: We did not find
      evidence supporting platinum-based adjuvant therapy for BOT with invasive
      implants.

PMID- 25601964
TI  - Dose-dense nonpegylated liposomal Doxorubicin and docetaxel combination in breast
      cancer: dose-finding study.
AB  - BACKGROUND: Anthracyclines and taxanes are effective drugs in breast cancer (BC),
      but their toxicity profiles limit their use in combination. A dose-finding study
      was performed to determine maximum tolerated doses (MTDs) of nonpegylated
      liposomal doxorubicin (TLC-D99) and docetaxel (DTX) as a dose-dense schedule, to
      maintain dose intensity, and to limit toxicity, particularly cardiac. METHODS:
      Twenty-four patients were enrolled, 12 with metastatic BC, 5 with locally
      advanced BC, and 7 with early BC. An intra- and interpatient approach was planned
      in two sequential steps. In the first step, TLC-D99 was administered at dose
      levels of 40, 45, and 50 mg/m(2) plus DTX at a fixed dose of 50 mg/m(2). In the
      second step, TLC-D99 was administered at the dose established in the first step
      plus DTX at dose levels of 55, 60, and 65 mg/m(2). Every treatment cycle was
      delivered on day 1 every 14 days. Pegylated granulocyte colony-stimulating factor
      was scheduled on day 2. Dose-limiting toxicities (DLTs) were defined as G4
      hematological; G3 nonhematological; >=10% or >=20% left ventricular ejection
      fraction (LVEF) reduction if the final value was <50% or >=50%, respectively;
      severe arrhythmia; and symptomatic heart failure. LVEF was evaluated by
      echocardiography every two cycles, and precursor brain natriuretic peptide (pBNP)
      and cardiac troponin I (cTnI) were monitored on days 1 and 2. RESULTS: Five DLTs
      occurred (20.8%). No cardiac event of congestive heart failure was reported; 2
      events of grade 3 cardiac dysfunction (8.3%), including a >=20% LVEF reduction in
      1 patient and symptomatic arrhythmia in another; 2 incidences of G4 neutropenia
      (8.3%); and 1 occurrence of G3 asthenia (4.2%) were reported. MTDs were not
      reached. The recommended doses were established as TLC-D99 50 mg/m(2) and DTX 65
      mg/m(2). Cumulatively, mild (G1-G2) cardiac dysfunction was observed in 58.4% of
      patients: G1 cardiac arrhythmia was noted in 50%, G1-G2 general cardiac toxicity
      occurred in 25%, and concomitant toxicity was present in 17%. cTnI never
      increased. pBNP was increased in 25% and was associated with limiting arrhythmia
      in 4% and cardiac dysfunction in 16%. CONCLUSION: Dose-dense TLC-D99 50 mg/m(2)
      and DTX 65 mg/m(2) can be safely administered in combination every 2 weeks for
      breast cancer, with the highest projected dose intensity for each drug at 25 and
      32.5 mg/m(2) per week, respectively.

PMID- 25601966
TI  - Standard versus continuous administration of capecitabine in metastatic breast
      cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a
      pharmacogenetic analysis.
AB  - BACKGROUND: The approved capecitabine regimen as monotherapy in metastatic breast
      cancer (MBC) is 1,250 mg/m(2) twice daily for 2 weeks on and 1 week off (Cint).
      Dose modifications are often required because of severe hand-foot syndrome (HFS).
      We tested a continuous regimen with a lower daily dose but a similar cumulative
      dose in an attempt to reduce the severity of adverse events (AEs) while
      maintaining efficacy. METHODS: We randomized 195 patients with HER-2/neu-negative
      MBC to capecitabine 800 mg/m(2) twice daily throughout the 21-day cycle (Ccont)
      or to Cint to assess noninferiority in the percentage of patients free of
      progression at 1 year. Secondary endpoints included efficacy and safety.
      Associations between polymorphisms in capecitabine metabolism-related genes and
      drug response were assessed. RESULTS: The percentage of patients free of
      progression at 1 year was 27.3% with Cint versus 25.3% with Ccont (difference of 
      2.0%; 95% confidence interval: -15.5% to 11.5%, exceeding the 15% deemed
      noninferior). Differences regarding other efficacy variables were also not found.
      Grade 3-4 HFS was the most frequent AE (41.1% in Cint vs. 42.3% in Ccont). Grade
      3-4 neutropenia, thrombocytopenia, diarrhea, and stomatitis were more frequent
      with Cint. A 5' untranslated region polymorphism in the carboxylesterase 2 gene
      was associated with HFS. One polymorphism in cytidine deaminase and two in
      thymidine phosphorylase were associated with survival. CONCLUSION: Our study was
      unable to show noninferiority with the continuous capecitabine regimen (Ccont)
      compared with the approved intermittent regimen (Cint). Further investigation is
      required to improve HFS. Polymorphisms in several genes might contribute to
      interindividual differences in response to capecitabine.

PMID- 25601965
TI  - Is there a role for oral or intravenous ascorbate (vitamin C) in treating
      patients with cancer? A systematic review.
AB  - BACKGROUND: Many cancer patients receive supplemental ascorbate (vitamin C) in
      the belief that it synergizes the anticancer effects of chemotherapy and reduces
      its toxicity. METHODS: A systematic review was performed to evaluate the
      antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March
      2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to
      March 2014) were searched for randomized and observational studies. RESULTS: Of
      696 identified records, 61 full-text articles were screened and 34 were included.
      In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials
      (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267)
      were identified. Because of study heterogeneity, no meta-analyses were performed.
      No RCTs reported any statistically significant improvements in overall or
      progression-free survival or reduced toxicity with ascorbate relative to control
      arm. Evidence for ascorbate's antitumor effects was limited to case reports and
      observational and uncontrolled studies. CONCLUSION: There is no high-quality
      evidence to suggest that ascorbate supplementation in cancer patients either
      enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the
      high financial and time costs to patients of this treatment, high-quality placebo
      controlled trials are needed.

PMID- 25601967
TI  - A survey on characteristics of Japanese academic job market and evaluation.
AB  - BACKGROUND: During the Meiji era, at the end of the 19th century, Japan
      introduced western systems into many fields, economically developing later than
      other industrially developed countries. Japan introduced a higher education
      system modeled on the German system, focusing not on education but on research.
      The historical background has shaped contemporary Japanese academia differently
      from that of the United States and the European Union. In addition, because of
      geographical and linguistic barriers in Asia, intercommunication with researchers
      in other developed countries has been much less than that between the United
      States and the European Union, leaving Japanese academia relatively isolated.
      METHOD: We survey the characteristics of the Japanese academic system in higher
      education, using the latest published data. RESULT: This article indicates a
      concentration of research at former imperial universities and a rigidity of
      movement among universities both internationally and domestically. Furthermore,
      small differences in salary levels have provided little incentive to perform
      research. However, while most universities in Japan have not introduced
      evaluation systems for promotion and salary that are heavily dependent on journal
      rankings, as in the European Union and United States, Japanese academic
      performance has not declined. CONCLUSION: This article suggests that in Japan,
      salary incentives, the impact factor, and so on have had little influence on
      academic performance. Even though cultural and historical differences between
      countries affect academic behaviors, we hope that this article might trigger
      consideration of other possible evaluation schemes for the future.

PMID- 25601968
TI  - Integrative therapies in cancer: modulating a broad spectrum of targets for
      cancer management.
AB  - Integrative medicine is an approach to health and healing that "makes use of all
      appropriate therapeutic approaches, health care professionals, and disciplines to
      achieve optimal health and healing." A comprehensive integrative medicine
      intervention for cancer patients typically includes nutritional counseling,
      biobehavioral strategies, and promotion of physical activity, as well as dietary
      supplements including herbs, nutraceuticals, and phytochemicals. A broad-spectrum
      intervention of this type may contribute uniquely to improvement in cancer
      outcomes through its impact on a wide variety of relevant molecular targets,
      including effects on multiple cancer hallmarks. Hallmarks that may be
      particularly affected include genetic instability, tumor-promoting inflammation,
      deregulated metabolism, and immune system evasion. Because of their
      susceptibility to manipulation by diet, exercise, and supplementation, these may
      be characterized as metabolic hallmarks. Research on the use of comprehensive
      integrative approaches can contribute to the development of systems of
      multitargeted treatment regimens and would help clarify the combined effect of
      these approaches on cancer outcomes. 

PMID- 25601969
TI  - Analgesic effect of Chinese herbal formula Hua-Jian-Ba-Du ointment on visceral
      pain in mice induced by acetic acid.
AB  - INTRODUCTION: Visceral pain is one of the most important pains caused by cancer
      or other diseases, and most of the medications may lead to tolerance, addiction,
      and toxic side effects. Hua-Jian-Ba-Du Ointment (HJBDO), which is a commonly used
      conjugate based on traditional Chinese medicine theory, has been effective
      against visceral pain. Here, we verify the efficacy and underlying mechanism of
      HJBDO in an acetic-acid induced visceral pain model. METHODS: Mice were subjected
      to acetic acid with or without HJBDO. Hua-Jian-Ba-Du Ointment at low (7.5
      mL/kg*d), moderate (15 mL/kg*d), and high (30 mL/kg*d) dosages was applied on the
      abdomen, 3 times per day for 3 days. The acetic acid writhing test was used to
      evaluate antinociception. Interleukin-2 (IL-2) in serum, tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in
      peritoneal fluid were detected by ELISA. 5-hydroxytryptamine (5-HT),
      norepinephrine (NE), dopamine (DA), and beta-endorphin (beta-EP) were examined by
      high performance liquid chromatography and radioimmunoassay, respectively. N
      methyl-D-aspartic acid receptor (NMDAR1) and c-fos expressions in both rostral
      ventromedial medulla (RVM) and spinal dorsal horn were determined by western
      blot. RESULTS: Hua-Jian-Ba-Du Ointment at 3 dosage levels produced dose-dependent
      antinociception and shortened the latent time. Hua-Jian-Ba-Du Ointment at high or
      moderate dosage inhibited the release of TNF-alpha, IL-6, and PGE2, as well as
      increased the release of IL-2. Hua-Jian-Ba-Du Ointment could also increase NE and
      5-HT contents and decrease the NE content. No effect of HJBDO at 3 dosages on the
      DA system was detected. Furthermore, HJBDO could suppress the expressions of
      NMDAR and c-fos in both RVM and spinal dorsal horn. CONCLUSION: Our results
      exhibited the analgesic effect of HJBDO on visceral pain in mice, and this effect
      might be mediated by the regulation of inflammation and neurotransmitters.

PMID- 25601970
TI  - Serum sCD95L concentration in patients with spinal cord injury.
AB  - OBJECTIVE: To determine serum concentrations of soluble CD95 ligand (sCD95L) in
      patients with traumatic spinal cord injury. METHODS: Patients with traumatic
      spinal cord injury were recruited. Blood was collected on admission to hospital
      and at 4 h, 9 h, 12 h, 24 h, 3 days, 7 days, and 2, 4, 8 and 12 weeks
      postadmission. Serum concentrations of sCD95L were determined via immunoassay.
      RESULT: The study included 23 patients. Mean sCD95L concentrations were
      significantly lower at 4 h, 9 h, 12 h and 24 h than at admission, and were
      significantly higher at 8 and 12 weeks, compared with admission. CONCLUSION: The
      serum sCD95L concentration fell significantly during the first 24 h after
      traumatic spinal cord injury. Concentrations then rose, becoming significantly
      higher than admission levels at 8 weeks. sCD95L may represent a possible
      therapeutic target for traumatic spinal cord injury.

PMID- 25601971
TI  - Geographic clusters in underimmunization and vaccine refusal.
AB  - BACKGROUND AND OBJECTIVE: Parental refusal and delay of childhood vaccines has
      increased in recent years and is believed to cluster in some communities. Such
      clusters could pose public health risks and barriers to achieving immunization
      quality benchmarks. Our aims were to (1) describe geographic clusters of
      underimmunization and vaccine refusal, (2) compare clusters of underimmunization
      with different vaccines, and (3) evaluate whether vaccine refusal clusters may
      pose barriers to achieving high immunization rates. METHODS: We analyzed
      electronic health records among children born between 2000 and 2011 with
      membership in Kaiser Permanente Northern California. The study population
      included 154,424 children in 13 counties with continuous membership from birth to
      36 months of age. We used spatial scan statistics to identify clusters of
      underimmunization (having missed 1 or more vaccines by 36 months of age) and
      vaccine refusal (based on International Classification of Diseases, Ninth
      Revision, Clinical Modification codes). RESULTS: We identified 5 statistically
      significant clusters of underimmunization among children who turned 36 months old
      during 2010-2012. The underimmunization rate within clusters ranged from 18% to
      23%, and the rate outside them was 11%. Children in the most statistically
      significant cluster had 1.58 (P < .001) times the rate of underimmunization as
      others. Underimmunization with measles, mumps, rubella vaccine and varicella
      vaccines clustered in similar geographic areas. Vaccine refusal also clustered,
      with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them.
      CONCLUSIONS: Underimmunization and vaccine refusal cluster geographically.
      Spatial scan statistics may be a useful tool to identify locations with
      challenges to achieving high immunization rates, which deserve focused
      intervention.

PMID- 25601972
TI  - Redefining success in the PICU: new patient populations shift targets of care.

PMID- 25601973
TI  - Energy and nutrient intake from pizza in the United States.
AB  - BACKGROUND AND OBJECTIVE: Pizza consumption is a top contributor to children's
      and adolescents' caloric intake. The objective of this study was to examine
      children's and adolescents' pizza consumption patterns and its impact on their
      energy and nutrient intake. METHODS: Twenty-four-hour dietary recall data for
      children aged 2 to 11 and adolescents aged 12 to 19 were drawn from the 2003
      2004, 2005-2006, 2007-2008, and 2009-2010 National Health and Nutrition
      Examination Survey. We tested changes in consumption patterns, including by
      race/ethnicity, income, meal occasion, and source. Individual-level fixed effects
      regression models estimated the impact of pizza consumption on total energy
      intake (TEI) and intakes of sugar, saturated fat, and sodium. RESULTS: From 2003
      2004 to 2009-2010, overall energy intake from pizza declined 25% among children
      (110 to 83 kcal, P <= .05). Among adolescents, although caloric intake from pizza
      among those who consumed pizza fell (801 to 624 kcal, P <= .05), overall pizza
      intake remained unchanged due to slightly higher pizza consumption prevalence.
      For children and adolescents, pizza intake fell (P <= .05) at dinner time and
      from fast food. For children and adolescents, respectively, pizza consumption was
      significantly associated with higher net daily TEI (84 kcal and 230 kcal) and
      higher intakes of saturated fat (3 g and 5 g) and sodium (134 mg and 484 mg) but
      not sugar intake, and such affects generally did not differ by sociodemographic
      characteristics. Pizza consumption as a snack or from fast-food restaurants had
      the greatest adverse impact on TEI. CONCLUSIONS: The adverse dietary effects of
      pizza consumption found in this study suggest that its consumption should be
      curbed and its nutrient content improved.

PMID- 25601974
TI  - Regional variation in antenatal corticosteroid use: a network-level quality
      improvement study.
AB  - BACKGROUND AND OBJECTIVES: Examination of regional care patterns in antenatal
      corticosteroid use (ACU) rates may be salient for the development of targeted
      interventions. Our objective was to assess network-level variation using
      California perinatal care regions as a proxy. We hypothesized that (1)
      significant variation in ACU exists within and between California perinatal care
      regions, and (2) lower performing regions exhibit greater NICU-level variability
      in ACU than higher performing regions. METHODS: We undertook cross-sectional
      analysis of 33,610 very low birth weight infants cared for at 120 hospitals in 11
      California perinatal care regions from 2005 to 2011. We computed risk-adjusted
      median ACU rates and interquartile ranges (IQR) for each perinatal care region.
      The degree of variation was assessed using hierarchical multivariate regression
      analysis with NICU as a random effect and region as a fixed effect. RESULTS: From
      2005 to 2011, mean ACU rates across California increased from 82% to 87.9%.
      Regional median (IQR) ACU rates ranged from 68.4% (24.3) to 92.9% (4.8). We found
      significant variation in ACU rates among regions (P < .0001). Compared with Level
      IV NICUs, care in a lower level of care was a strongly significant predictor of
      lower odds of receiving antenatal corticosteroids in a multilevel model (Level
      III, 0.65 [0.45-0.95]; Level II, 0.39 [0.24-0.64]; P < .001). Regions with lower
      performance in ACU exhibited greater variability in performance. CONCLUSIONS: We
      found significant variation in ACU rates among California perinatal regions.
      Regional quality improvement approaches may offer a new avenue to spread best
      practice.

PMID- 25601975
TI  - Transcutaneous bilirubin measurement: does it work in the real world?

PMID- 25601976
TI  - Diagnosing significant PDA using natriuretic peptides in preterm neonates: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVES: Echocardiogram is the gold standard for the diagnosis
      of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm
      neonates. A simple blood assay for brain natriuretic peptide (BNP) or amino
      terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in the
      diagnosis and management of hsPDA. Our objectives were to determine the
      diagnostic accuracy of BNP and NT-proBNP for hsPDA in preterm neonates and to
      explore heterogeneity by analyzing subgroups. METHODS: The systematic review was
      performed as recommended by the Cochrane Diagnostic Test Accuracy Working Group.
      Electronic databases, conference abstracts, and cross-references were searched.
      We included studies that evaluated BNP or NT-proBNP (index test) in preterm
      neonates with suspected hsPDA (participants) in comparison with echocardiogram
      (reference standard). A bivariate random effects model was used for meta
      analysis, and summary receiver operating characteristic curves were generated.
      RESULTS: Ten BNP and 11 NT-proBNP studies were included. Studies varied by
      methodological quality, type of commercial assay, thresholds, age at testing,
      gestational age, and whether the assay was used to initiate medical or surgical
      therapy. Sensitivity and specificity for BNP at summary point were 88% and 92%,
      respectively, and for NT-proBNP they were 90% and 84%, respectively. CONCLUSIONS:
      The studies evaluating the diagnostic accuracy of BNP and NT-proBNP for hsPDA
      varied widely by assay characteristics (assay kit and threshold) and patient
      characteristics (gestational and chronological age); therefore, generalizability
      between centers is not possible. We recommend that BNP or NT-proBNP assays be
      locally validated for specific patient population and outcomes, to initiate
      therapy or follow response to therapy.

PMID- 25601978
TI  - Cardiovascular risk factors in children after repeat doses of antenatal
      glucocorticoids: an RCT.
AB  - BACKGROUND: Treatment of women at risk for preterm birth with repeat doses of
      glucocorticoids reduces neonatal morbidity but could have adverse long-term
      effects on cardiometabolic health in offspring. We assessed whether exposure to
      repeat antenatal betamethasone increased risk factors for later cardiometabolic
      disease in children whose mothers participated in the Australasian Collaborative
      Trial of Repeat Doses of Corticosteroids. METHODS: Women were randomized to
      betamethasone or placebo treatment, >= 7 days after an initial course of
      glucocorticoids, repeated each week that they remained at risk for preterm birth
      at <32 weeks' gestation. In this follow-up study, children were assessed at 6 to
      8 years' corrected age for body composition, insulin sensitivity, ambulatory
      blood pressure, and renal function. RESULTS: Of 320 eligible childhood survivors,
      258 were studied (81%; 123 repeat betamethasone group; 135 placebo [single
      course] group). Children exposed to repeat antenatal betamethasone and those
      exposed to placebo had similar total fat mass (geometric mean ratio 0.98, 95%
      confidence interval [CI] 0.78 to 1.23), minimal model insulin sensitivity
      (geometric mean ratio 0.89, 95% CI 0.74 to 1.08), 24-hour ambulatory blood
      pressure (mean difference systolic 0 mm Hg, 95% CI -2 to 2; diastolic 0 mm Hg,
      95% CI -1 to 1), and estimated glomerular filtration rate (mean difference 1.2
      mL/min/1.73 m(2), 95% CI -3.2 to 5.6). CONCLUSIONS: Exposure to repeat doses of
      antenatal betamethasone compared with a single course of glucocorticoids does not
      increase risk factors for cardiometabolic disease at early school age.

PMID- 25601980
TI  - Tapentadol toxicity in children.
AB  - BACKGROUND: Tapentadol (Nucynta) is indicated for the treatment of moderate to
      severe pain in adults. Tapentadol's mechanism of action consists of acting as an
      agonist on the MU-opioid receptor and by inhibiting the reuptake of
      norepinephrine. There are no published reports on the toxicity of tapentadol in
      pediatric patients. The goals of this study are to describe the incidence,
      medical outcomes, clinical effects, and treatment secondary to tapentadol
      exposure. METHODS: This retrospective observational study used data from the
      National Poison Data System. Inclusion criteria were exposure to tapentadol from
      November 1, 2008 to December 31, 2013; age 0 to 17 years; single ingestion; and
      followed to a known outcome. RESULTS: There were 104 patients who met the
      inclusion criteria. Eighty patients were aged <= 6, 2-year-olds the most common
      age group (60.6%). There were 52 male and 52 female patients. Of the 104
      patients, 93 had unintentional exposures. No deaths were reported. Sixty-two of
      the patients had no effect, 34 had minor effects, 6 had moderate and 2 had major
      effects. Thirty patients reported drowsiness and lethargy. Other effects reported
      included nausea, vomiting, miosis, tachycardia, respiratory depression,
      dizziness/vertigo, coma, dyspnea, pallor, vomiting, edema, hives/welts, slurred
      speech, pruritus, and hallucinations/delusions. Fifty-three patients were
      reported to have no medical intervention. CONCLUSIONS: This is the first study
      examining the toxic effects of tapentadol in a pediatric population. Although a
      majority of the patients in this review developed no effect from their exposure,
      two had life-threatening events. The most common effects reported were
      opioidlike.

PMID- 25601979
TI  - Quality of life and obstructive sleep apnea symptoms after pediatric
      adenotonsillectomy.
AB  - BACKGROUND AND OBJECTIVES: Data from a randomized, controlled study of
      adenotonsillectomy for obstructive sleep apnea syndrome (OSAS) were used to test
      the hypothesis that children undergoing surgery had greater quality of life (QoL)
      and symptom improvement than control subjects. The objectives were to compare
      changes in validated QoL and symptom measurements among children randomized to
      undergo adenotonsillectomy or watchful waiting; to determine whether race,
      weight, or baseline OSAS severity influenced changes in QoL and symptoms; and to
      evaluate associations between changes in QoL or symptoms and OSAS severity.
      METHODS: Children aged 5 to 9.9 years with OSAS (N = 453) were randomly assigned
      to undergo adenotonsillectomy or watchful waiting with supportive care.
      Polysomnography, the Pediatric Quality of Life inventory, the Sleep-Related
      Breathing Scale of the Pediatric Sleep Questionnaire, the 18-item Obstructive
      Sleep Apnea QoL instrument, and the modified Epworth Sleepiness Scale were
      completed at baseline and 7 months. Changes in the QoL and symptom surveys were
      compared between arms. Effect modification according to race and obesity and
      associations between changes in polysomnographic measures and QoL or symptoms
      were examined. RESULTS: Greater improvements in most QoL and symptom severity
      measurements were observed in children randomized to undergo adenotonsillectomy,
      including the parent-completed Pediatric Quality of Life inventory (effect size
      [ES]: 0.37), the 18-item Obstructive Sleep Apnea QoL instrument (ES: -0.93), the
      modified Epworth Sleepiness Scale score (ES: -0.42), and the Sleep-Related
      Breathing Scale of the Pediatric Sleep Questionnaire (ES: -1.35). Effect
      modification was not observed by obesity or baseline severity but was noted for
      race in some symptom measures. Improvements in OSAS severity explained only a
      small portion of the observed changes. CONCLUSIONS: Adenotonsillectomy compared
      with watchful waiting resulted in significantly more improvements in parent-rated
      generic and OSAS-specific QoL measures and OSAS symptoms.

PMID- 25601981
TI  - Discrepancies between transcutaneous and serum bilirubin measurements.
AB  - OBJECTIVE: To characterize discrepancies between transcutaneous bilirubin (TcB)
      measurements and total serum bilirubin (TSB) levels among newborns receiving care
      at multiple nursery sites across the United States. METHODS: Medical records were
      reviewed to obtain data on all TcB measurements collected during two 2-week
      periods on neonates admitted to participating newborn nurseries. Data on TSB
      levels obtained within 2 hours of a TcB measurement were also abstracted. TcB-
      TSB differences and correlations between the values were determined. Data on
      demographic information for individual newborns and TcB screening practices for
      each nursery were also collected. Multivariate regression analysis was used to
      identify characteristics independently associated with the TcB--TSB difference.
      RESULTS: Data on 8319 TcB measurements were collected at 27 nursery sites; 925
      TSB levels were matched to a TcB value. The mean TcB--TSB difference was 0.84 +/-
      1.78 mg/dL, and the correlation between paired measurements was 0.78. In the
      multivariate analysis, TcB--TSB differences were 0.67 mg/dL higher in African
      American newborns than in neonates of other races (P < .001). The TcB--TSB
      difference also varied significantly based on brand of TcB meter used and hour of
      age of the infant. For 2.2% of paired measurements, the TcB measurement
      underestimated the TSB level by >= 3 mg/dL. CONCLUSIONS: During routine clinical
      care, TcB measurement provided a reasonable estimate of TSB levels in healthy
      newborns. Discrepancies between TcB and TSB levels were increased in African
      American newborns and varied based on brand of meter used.

PMID- 25601982
TI  - Development of hospital-based guidelines for skeletal survey in young children
      with bruises.
AB  - OBJECTIVE: To develop guidelines for performing an initial skeletal survey (SS)
      for children <24 months of age presenting with bruising in the hospital setting,
      combining available evidence with expert opinion. METHODS: Applying the Rand/UCLA
      Appropriateness Method, a multispecialty panel of 10 experts relied on evidence
      from the literature and their own clinical expertise in rating the
      appropriateness of performing SS for 198 clinical scenarios characterizing
      children <24 months old with bruising. After a moderated discussion of initial
      ratings, the scenarios were revised. Panelists re-rated SS appropriateness for
      219 revised scenarios. For the 136 clinical scenarios in which SS was deemed
      appropriate, the panel finally assessed the necessity of SS. RESULTS: Panelists
      agreed that SS is "appropriate" for 62% (136/219) of scenarios, and
      "inappropriate" for children >= 12 months old with nonpatterned bruising on bony
      prominences. Panelists agreed that SS is "necessary" for 95% (129/136) of the
      appropriate scenarios. SS was deemed necessary for infants <6 months old
      regardless of bruise location, with rare exceptions, but the necessity of SS in
      older children depends on bruise location. According to the panelists, bruising
      on the cheek, eye area, ear, neck, upper arm, upper leg, hand, foot, torso,
      buttock, or genital area necessitates SS in children <12 months. CONCLUSIONS: The
      appropriateness and necessity of SS in children presenting for care to the
      hospital setting with bruising, as determined by a diverse panel of experts,
      depends on age of the child and location of bruising.

PMID- 25601983
TI  - Cognitive ability at kindergarten entry and socioeconomic status.
AB  - OBJECTIVE: To examine how gradients in socioeconomic status (SES) impact US
      children's reading and math ability at kindergarten entry and determine the
      contributions of family background, health, home learning, parenting, and early
      education factors to those gradients. METHODS: Analysis of 6600 children with
      cognitive assessments at kindergarten entry from the US Early Childhood
      Longitudinal Birth Cohort Study. A composite SES measure based on parent's
      occupation, education, and income was divided into quintiles. Wald F tests
      assessed bivariate associations between SES and child's cognitive ability and
      candidate explanatory variables. A decomposition methodology examined mediators
      of early cognitive gradients. RESULTS: Average reading percentile rankings
      increased from 34 to 67 across SES quintiles and math from 33 to 70. Children in
      lower SES quintiles had younger mothers, less frequent parent reading, less home
      computer use (27%-84%), and fewer books at home (26-114). Parent's supportive
      interactions, expectations for their child to earn a college degree (57%-96%),
      and child's preschool attendance (64%-89%) increased across quintiles. Candidate
      explanatory factors explained just over half the gradients, with family
      background factors explaining 8% to 13%, health factors 4% to 6%, home learning
      environment 18%, parenting style/beliefs 14% to 15%, and early education 6% to 7%
      of the gaps between the lowest versus highest quintiles in reading and math.
      CONCLUSIONS: Steep social gradients in cognitive outcomes at kindergarten are due
      to many factors. Findings suggest policies targeting levels of socioeconomic
      inequality and a range of early childhood interventions are needed to address
      these disparities.

PMID- 25601984
TI  - Quality improvement measures in pulse-oximetry newborn heart screening: a time
      series analysis.
AB  - BACKGROUND AND OBJECTIVES: The use of pulse-oximetry screening to detect critical
      congenital heart defects in newborns has gained national and international
      momentum in the past decade. Our hospital system began screening in 2008. Since
      then, our program has undergone leadership changes and multiple quality
      improvement interventions. The aims of this study are to evaluate the evolution
      of our pulse-oximetry program and to provide insights from lessons learned over
      the course of a long-standing program. METHODS: We reviewed 6 years of screening
      data and evaluated trends of missed screens, false-positives, protocol
      violations, and parental decline of screening. We implemented 3 quality
      improvement interventions (change in protocol, redesign of an electronic medical
      record documentation system to autocalculate results, and transition from
      research to standard-of-care) and reviewed the impact of a rigorous quality
      assurance review process. We used linear regression and statistical process
      control charts to evaluate the data. RESULTS: A total of 18,363 newborns were
      screened; we identified 5 critical cases. We observed a significant decrease in
      missed (P < .001) and false-positive (P = .03) screens over time but found no
      significant trend in the rate of percentage of protocol violations (P = .26) or
      decline of screening (P = .99). Each metric showed behavior attributable to at
      least 1 quality improvement intervention. CONCLUSIONS: We established a
      sustainable pulse-oximetry screening program in our community hospital system,
      and the screening has now become routine. The quality of our screening was
      influenced by choice of screening protocol, rigor of quality assurance reviews,
      and the process used to interpret screening results.

PMID- 25601985
TI  - Heterogeneity in asthma care in a statewide collaborative: the Ohio Pediatric
      Asthma Repository.
AB  - BACKGROUND AND OBJECTIVE: Asthma heterogeneity causes difficulty in studying and
      treating the disease. We built a comprehensive statewide repository linking
      questionnaire and medical record data with health outcomes to characterize the
      variability of clinical practices at Ohio children's hospitals for the treatment
      of hospitalized asthma. METHODS: Children hospitalized at 6 participating Ohio
      children's hospitals for asthma exacerbation or reactive airway disease aged 2 to
      17 were eligible. Medical, social, and environmental histories and past asthma
      admissions were collected from questionnaires and the medical record. RESULTS:
      From December 2012 to September 2013, 1012 children were enrolled. There were
      significant differences in the population served, emergency department and
      inpatient practices, intensive care unit usage, discharge criteria, and length of
      stay across the sites (all P < .0001, total n = 1012). Public insurance was
      highest in Cleveland and Cincinnati (72 and 65%). In the emergency department,
      Cincinnati and Akron had the highest intravenous magnesium sulfate use (37% and
      33%); Columbus administered the most intramuscular epinephrine (15%). Cleveland
      and Columbus had the highest intensive care unit admittance (44% and 41%) and
      proportion of long-stay patients (95% and 85%). Moderate/severe asthma severity
      classification was associated with discharge prescription for inhaled
      corticosteroids (odds ratio = 2.7; 95% confidence interval: 1.6-4.5; P = .004)
      but not stay length. CONCLUSIONS: These data highlight the need for
      standardization of treatment practices for inpatient asthma care. There is
      considerable opportunity for personalized care plans that incorporate a patient's
      asthma impairment, risk, and treatment response history into hospital practices
      for asthma exacerbation treatment. The Ohio Pediatric Asthma Repository is a
      unique statewide resource in which to conduct observational, comparative
      effectiveness, and ultimately intervention studies for pediatric asthma.

PMID- 25601987
TI  - Orotic acid induces hypertension associated with impaired endothelial nitric
      oxide synthesis.
AB  - Orotic acid (OA) is an intermediate of pyrimidine nucleotide biosynthesis.
      Hereditary deficiencies in some enzymes associated with pyrimidine synthesis or
      the urea cycle induce OA accumulation, resulting in orotic aciduria. A link
      between patients with orotic aciduria and hypertension has been reported;
      however, the molecular mechanisms remain elusive. In this study, to elucidate the
      role of OA in vascular insulin resistance, we investigated whether OA induced
      endothelial dysfunction and hypertension. OA inhibited insulin- or metformin
      stimulated nitric oxide (NO) production and endothelial NO synthase (eNOS)
      phosphorylation in human umbilical vein endothelial cells. A decreased insulin
      response by OA was mediated by impairment of the insulin-stimulated
      phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB/Akt) signaling pathway in
      cells overexpressing the p110-PI3K catalytic subunit. Impaired effects of
      metformin on eNOS phosphorylation and NO production were reversed in cells
      transfected with constitutively active AMP-activated protein kinase. Moreover,
      experimental induction of orotic aciduria in rats caused insulin resistance,
      measured as a 125% increase in the homeostasis model assessment, and
      hypertension, measured as a 25% increase in systolic blood pressure. OA increased
      the plasma concentration of endothelin-1 by 201% and significantly inhibited
      insulin- or metformin-induced vasodilation. A compromised insulin or metformin
      response on the Akt/eNOS and AMP-activated protein kinase/eNOS pathway was
      observed in aortic rings of OA-fed rats. Taken together, we showed that OA
      induces endothelial dysfunction by contributing to vascular and systemic insulin
      resistance that affects insulin- or metformin-induced NO production, leading to
      the development of hypertension. 

PMID- 25601986
TI  - Oral methylphenidate alleviates the fine motor dysfunction caused by chronic
      postnatal manganese exposure in adult rats.
AB  - Developmental manganese (Mn) exposure is associated with motor dysfunction in
      children and animal models, but little is known about the underlying
      neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We
      investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due
      to chronic postnatal Mn exposure, and whether Mn exposure impairs brain
      extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex
      (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg
      Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The
      staircase test was used to assess skilled forelimb function. Oral MPH (2.5
      mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA
      and NE levels were measured by dual probe microdialysis. Results show that Mn
      exposure impaired reaching and grasping skills and the evoked release of DA and
      NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully
      alleviated the fine motor deficits in the Mn-exposed animals, but did not affect
      forelimb skills of control rats not exposed to Mn. These results suggest that
      catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn
      induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective
      treatment approach for alleviating this dysfunction in adult animals. The
      therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed
      children and adults appears promising pending further characterization of MPH
      efficacy in other functional areas (eg, attention) believed to be affected by
      developmental Mn exposure.

PMID- 25601989
TI  - Human inhalation exposures to toluene, ethylbenzene, and m-xylene and
      physiologically based pharmacokinetic modeling of exposure biomarkers in exhaled
      air, blood, and urine.
AB  - Urinary biomarkers of exposure are used widely in biomonitoring studies. The
      commonly used urinary biomarkers for the aromatic solvents toluene (T),
      ethylbenzene (E), and m-xylene (X) are o-cresol, mandelic acid, and m
      methylhippuric acid. The toxicokinetics of these biomarkers following inhalation
      exposure have yet to be described by physiologically based pharmacokinetic (PBPK)
      modeling. Five male volunteers were exposed for 6 h in an inhalation chamber to
      1/8 or 1/4 of the time-weighted average exposure value (TWAEV) for each solvent:
      toluene, ethylbenzene, and m-xylene were quantified in blood and exhaled air and
      their corresponding urine biomarkers were measured in urine. Published PBPK model
      for parent compounds was used and simulations were compared with experimental
      blood and exhaled air concentration data. If discrepancies existed, Vmax and Km
      were optimized. Urinary excretion was modeled using parameters found in
      literature assuming simply stoichiometric yields from parent compound metabolism
      and first-order urinary excretion rate. Alternative models were also tested for
      (1) the possibility that CYP1A2 is the only enzyme implicated in o-cresol and (2)
      a 2-step model for describing serial metabolic steps for mandelic acid. Models
      adapted in this study for urinary excretion will be further used to interpret
      urinary biomarker kinetic data from mixed exposures of these solvents. 

PMID- 25601988
TI  - Methylmercury impairs canonical dopamine metabolism in rat undifferentiated
      pheochromocytoma (PC12) cells by indirect inhibition of aldehyde dehydrogenase.
AB  - The environmental neurotoxicant methylmercury (MeHg) disrupts dopamine (DA)
      neurochemical homeostasis by stimulating DA synthesis and release. Evidence also
      suggests that DA metabolism is independently impaired. The present investigation
      was designed to characterize the DA metabolomic profile induced by MeHg, and
      examine potential mechanisms by which MeHg inhibits the DA metabolic enzyme
      aldehyde dehydrogenase (ALDH) in rat undifferentiated PC12 cells. MeHg decreases
      the intracellular concentration of 3,4-dihydroxyphenylacetic acid (DOPAC). This
      is associated with a concomitant increase in intracellular concentrations of the
      intermediate metabolite 3,4-dihydroxyphenylaldehyde (DOPAL) and the reduced
      metabolic product 3,4-dihydroxyethanol. This metabolomic profile is consistent
      with inhibition of ALDH, which catalyzes oxidation of DOPAL to DOPAC. MeHg does
      not directly impair ALDH enzymatic activity, however MeHg depletes cytosolic
      levels of the ALDH cofactor NAD(+), which could contribute to impaired ALDH
      activity following exposure to MeHg. The observation that MeHg shunts DA
      metabolism along an alternative metabolic pathway and leads to the accumulation
      of DOPAL, a reactive species associated with protein and DNA damage, as well as
      cell death, is of significant consequence. As a specific metabolite of DA, the
      observed accumulation of DOPAL provides evidence for a specific mechanism by
      which DA neurons may be selectively vulnerable to MeHg. 

PMID- 25601992
TI  - Correction.

PMID- 25601990
TI  - N-hydroxylation of 4-aminobiphenyl by CYP2E1 produces oxidative stress in a mouse
      model of chemically induced liver cancer.
AB  - 4-Aminobiphenyl (ABP) is a trace component of cigarette smoke and hair dyes, a
      suspected human carcinogen and a potent rodent liver carcinogen. Postnatal
      exposure of mice to ABP results in a higher incidence of liver tumors in males
      than in females, paralleling the sex difference in human liver cancer incidence.
      A traditional model of ABP tumorigenesis involves initial CYP1A2-mediated N
      hydroxylation, which eventually leads to production of mutagenic ABP-DNA adducts
      that initiate tumor growth. However, several studies have found no correlation
      between sex or CYP1A2 function and the DNA-damaging, mutagenic, or tumorigenic
      effects of ABP. Oxidative stress may be an important etiological factor for liver
      cancer, and it has also been linked to ABP exposure. The goals of this study were
      to identify novel enzyme(s) that contribute to ABP N-oxidation, and to
      investigate a potential role for oxidative stress in ABP liver tumorigenicity.
      Isozyme-selective inhibition experiments using liver microsomes from wild-type
      and genetically modified mice identified CYP2E1 as a major ABP N-hydroxylating
      enzyme. The N-hydroxylation of ABP by transiently expressed CYP2E1 produced
      oxidative stress in cultured mouse hepatoma cells. In vivo postnatal exposure of
      mice to a tumorigenic dose of ABP also produced oxidative stress in male wild
      type mice, but not in male Cyp2e1(-/-) mice or in female mice. However, a
      stronger NRF2-associated antioxidant response was observed in females. Our
      results identify CYP2E1 as a novel ABP-N-oxidizing enzyme, and suggest that sex
      differences in CYP2E1-dependent oxidative stress and antioxidant responses to ABP
      may contribute to the observed sex difference in tumor incidence.

PMID- 25601977
TI  - Age at gluten introduction and risk of celiac disease.
AB  - OBJECTIVES: The goal of this study was to determine whether age at introduction
      to gluten was associated with risk for celiac disease (CD) in genetically
      predisposed children. METHODS: TEDDY (The Environmental Determinants of Diabetes
      in the Young) is a prospective birth cohort study. Newborn infants (N = 6436)
      screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany,
      Sweden, and the United States. Information about infant feeding was collected at
      clinical visits every third month. The first outcome was persistent positive for
      tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second
      outcome was CD, defined as either a diagnosis based on intestinal biopsy results
      or on persistently high levels of tTGA. RESULTS: Swedish children were introduced
      to gluten earlier (median: 21.7 weeks) compared with children from Finland
      (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P
      < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773
      (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at
      increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard
      ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P <
      .0001).Gluten introduction before 17 weeks or later than 26 weeks was not
      associated with increased risk for tTGA or CD, adjusted for country, HLA, gender,
      and family history of CD, neither in the overall analysis nor on a country-level
      comparison. CONCLUSIONS: In TEDDY, the time to first introduction to gluten
      introduction was not an independent risk factor for developing CD.

PMID- 25601991
TI  - Cell type-dependent changes in CdSe/ZnS quantum dot uptake and toxic endpoints.
AB  - Toxicity of nanoparticles (NPs) is often correlated with the physicochemical
      characteristics of the materials. However, some discrepancies are noted in in
      vitro studies on quantum dots (QDs) with similar physicochemical properties. This
      is partly related to variations in cell type. In this study, we show that
      epithelial (BEAS-2B), fibroblast (HFF-1), and lymphoblastoid (TK6) cells show
      different biological responses following exposure to QDs. These cells represented
      the 3 main portals of NP exposure: bronchial, skin, and circulatory. The uptake
      and toxicity of negatively and positively charged CdSe:ZnS QDs of the same core
      size but with different surface chemistries (carboxyl or amine polymer coatings)
      were investigated in full and reduced serum containing media following 1 and 3
      cell cycles. Following thorough physicochemical characterization, cellular
      uptake, cytotoxicity, and gross chromosomal damage were measured. Cellular damage
      mechanisms in the form of reactive oxygen species and the expression of
      inflammatory cytokines IL-8 and TNF-alpha were assessed. QDs uptake and toxicity
      significantly varied in the different cell lines. BEAS-2B cells demonstrated the
      highest level of QDs uptake yet displayed a strong resilience with minimal
      genotoxicity following exposure to these NPs. In contrast, HFF-1 and TK6 cells
      were more susceptible to toxicity and genotoxicity, respectively, as a result of
      exposure to QDs. Thus, this study demonstrates that in addition to nanomaterial
      physicochemical characterization, a clear understanding of cell type-dependent
      variation in uptake coupled to the inherently different capacities of the cell
      types to cope with exposure to these exogenous materials are all required to
      predict genotoxicity. 

PMID- 25601993
TI  - Therapeutic efficacy of chloroquine for the treatment of uncomplicated Plasmodium
      falciparum in Haiti after many decades of its use.
AB  - Chloroquine (CQ) has been used for malaria treatment in Haiti for several
      decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients
      with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was
      evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a
      42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The
      P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was
      seasonal, with peak observations between October and January; 88% (107 of 121) of
      patients consented to participate. Sixty patients successfully completed the 42
      day follow-up, whereas 47 patients withdrew consent or were lost to follow-up.
      The mean parasite density declined rapidly within the first few days after
      treatment. Seven patients did not clear their malaria infections and were
      clinically asymptomatic; therefore, they were considered late parasitological
      failures. About 90% (95% confidence interval = 84.20-97.90) of patients had no
      detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for
      recrudescence, reinfection, and CQ serum levels was not done in the seven
      patients, and therefore, their CQ resistance status is unresolved. CQ resistance
      surveillance by patient follow-up, in vitro drug sensitivity studies, and
      molecular markers is urgently needed in Haiti. 

PMID- 25601994
TI  - Risk factors for border malaria in a malaria elimination setting: a retrospective
      case-control study in Yunnan, China.
AB  - A retrospective case-control study was conducted to identify risk factors for
      border malaria in a malaria elimination setting of Yunnan Province, China. The
      study comprised 214 cases and 428 controls. The controls were individually
      matched to the cases on the basis of residence, age, and gender. In addition,
      statistical associations are based on matched analyses. The frequencies of
      imported, male, adult, and vivax malaria cases were respectively 201 (93.9%), 194
      (90.7%), 210 (98.1%), and 176 (82.2%). Overnight stay in Myanmar within the prior
      month was independently associated with malaria infection (odds ratio [OR] 159.5,
      95% confidence interval [CI] 75.1-338.9). In particular, stays in lowland and
      foothill (OR 5.5, 95% CI 2.5-11.8) or mid-hill (OR 42.8, 95% CI 5.1-319.8) areas,
      or near streamlets (OR 15.3, 95% CI 4.3-55.2) or paddy field or pools (OR10.1,
      95% CI 4.4-55.8) were found to be independently associated with malaria. Neither
      forest exposure nor use of vector control measures was associated with malaria.
      In conclusion, travel to lowland and foothill or mid-hill hyperendemic areas,
      especially along the waterside in Myanmar, was found to be the highest risk
      factor for malaria. In considering the limitations of the study, further
      investigations are needed to identify the major determinants of malaria risk and
      develop new strategies for malaria elimination on China-Myanmar border. 

PMID- 25601997
TI  - Exploring physician compensation.

PMID- 25601996
TI  - Chikungunya virus infection: first detection of imported and autochthonous cases
      in Panama.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne pathogen that was only endemic in
      Africa and south Asia until 2005 and 2006, when the virus spread into the Indian
      Ocean islands, Europe, and Asia. Autochthonous CHIKV transmission in the
      Caribbean islands was reported in December of 2013. In Panama, two febrile cases
      were detected in May of 2014: one traveling from Haiti, and the other traveling
      from the Dominican Republic. After other imported cases were detected, the first
      autochthonous case was reported in August of the same year. We detected CHIKV
      viral RNA and isolated the virus from serum samples. The phylogenetic analysis of
      the two imported isolates and one autochthonous CHIKV isolate indicated that the
      viruses belong to the Asian lineage in the Caribbean clade and are related to
      viruses recently identified in Saint Martin island, British Virgin Islands,
      China, and the Philippines. Although the circulating CHIKV lineages in the
      Americas have not yet been described, our results suggest that the Asian lineage
      is circulating in most American countries reporting autochthonous infection. 

PMID- 25601998
TI  - Lessons from health research luminaries.

PMID- 25601995
TI  - The ongoing revolution of MALDI-TOF mass spectrometry for microbiology reaches
      tropical Africa.
AB  - Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS) represents a revolution in routine pathogen identification in
      clinical microbiology laboratories. A MALDI-TOF MS was introduced to tropical
      Africa in the clinical microbiology laboratory of the Hopital Principal de Dakar
      (Senegal) and used for routine pathogen identification. Using MS, 2,429 bacteria
      and fungi isolated from patients were directly assayed, leading to the
      identification of 2,082 bacteria (85.7%) and 206 fungi (8.5%) at the species
      level, 109 bacteria (4.5%) at the genus level, and 16 bacteria (0.75%) at the
      family level. Sixteen isolates remained unidentified (0.75%). Escherichia coli
      was the most prevalent species (25.8%) followed by Klebsiella pneumoniae (14.8%),
      Streptococcus agalactiae (6.2%), Acinetobacter baumannii (6.1%), Pseudomonas
      aeruginosa (5.9%), and Staphylococcus aureus (5.9%). MALDI-TOF MS has also
      enabled the detection of rare bacteria and fungi. MALDI-TOF MS is a powerful tool
      for the identification of bacterial and fungal species involved in infectious
      diseases in tropical Africa. 

PMID- 25601999
TI  - Hypothyroidism.

PMID- 25602000
TI  - Restricting private-sector practice using contracts.

PMID- 25602002
TI  - St. Vitus' dance.

PMID- 25602001
TI  - Old meets new: identifying founder mutations in genetic disease.

PMID- 25602003
TI  - Where there's smoke, there's respiratory risk.

PMID- 25602004
TI  - 10 health stories that mattered: Jan. 10-16.

PMID- 25602005
TI  - Caring for Aboriginal patients requires trust and respect, not courtrooms.

PMID- 25602006
TI  - Right atrial mass in a 23-year-old woman with molar pregnancy.

PMID- 25602007
TI  - IVF booster offered in Canada but not US.

PMID- 25602008
TI  - A founder AGL mutation causing glycogen storage disease type IIIa in Inuit
      identified through whole-exome sequencing: a case series.
AB  - BACKGROUND: Glycogen storage disease type III is caused by mutations in both
      alleles of the AGL gene, which leads to reduced activity of glycogen-debranching
      enzyme. The clinical picture encompasses hypoglycemia, with glycogen accumulation
      leading to hepatomegaly and muscle involvement (skeletal and cardiac). We sought
      to identify the genetic cause of this disease within the Inuit community of
      Nunavik, in whom previous DNA sequencing had not identified such mutations.
      METHODS: Five Inuit children with a clinical and biochemical diagnosis of
      glycogen storage disease type IIIa were recruited to undergo genetic testing: 2
      underwent whole-exome sequencing and all 5 underwent Sanger sequencing to confirm
      the identified mutation. Selected DNA regions near the AGL gene were also
      sequenced to identify a potential founder effect in the community. In addition,
      control samples from 4 adults of European descent and 7 family members of the
      affected children were analyzed for the specific mutation by Sanger sequencing.
      RESULTS: We identified a homozygous frame-shift deletion, c.4456delT, in exon 33
      of the AGL gene in 2 children by whole-exome sequencing. Confirmation by Sanger
      sequencing showed the same mutation in all 5 patients, and 5 family members were
      found to be carriers. With the identification of this mutation in 5 probands, the
      estimated prevalence of genetically confirmed glycogen storage disease type IIIa
      in this region is among the highest worldwide (1:2500). Despite identical
      mutations, we saw variations in clinical features of the disease. INTERPRETATION:
      Our detection of a homozygous frameshift mutation in 5 Inuit children determines
      the cause of glycogen storage disease type IIIa and confirms a founder effect.

PMID- 25602009
TI  - Helicobacter pylori infection as a protective factor against multiple sclerosis
      risk in females.
AB  - BACKGROUND: In recent years, a relationship between Helicobacter pylori and many
      disease conditions has been reported, however, studies in its relationship with
      multiple sclerosis (MS) have had contradictory results. OBJECTIVE: To determine
      the association between the H. pylori infection and MS. METHODS: 550 patients
      with MS were included in the study and were matched by gender and year of birth
      to 299 controls. Patients were assessed for clinical and demographic parameters.
      An enzyme immunoassay was used to detect the presence of specific IgG antibodies
      against H. pylori in the serum sample of both groups. RESULTS: H. pylori
      seropositivity was found to be lower in the patients with MS than in controls
      (16% vs 21%) with the decrease pertaining to females (14% vs 22%, p=0.027) but
      not males (19% vs 20%, p=1.0). When adjusted for age at onset, year of birth and
      disease duration, H. pylori seropositive females presented with a lower
      disability score than seronegative females (p=0.049), while among males the
      reverse was true (p=0.025). There was no significant association between H.
      pylori seropositivity and relapse rate. CONCLUSIONS: Our results could reflect a
      protective role of H. pylori in the disease development. However, it may be that
      H. pylori infection is a surrogate marker for the 'hygiene hypothesis', a theory
      which postulates that early life infections are essential to prime the immune
      system and thus prevent allergic and autoimmune conditions later in life. The
      fact that the association between H. pylori seropositivity and MS risk was seen
      almost exclusively in females requires further investigation.

PMID- 25602010
TI  - Helicobacter pylori infection might prove the hygiene hypothesis in multiple
      sclerosis.

PMID- 25602011
TI  - Strength training under hypoxic conditions.

PMID- 25602012
TI  - Endurance exercise training programs intestinal lipid metabolism in a rat model
      of obesity and type 2 diabetes.
AB  - Endurance exercise has been shown to improve metabolic outcomes in obesity and
      type 2 diabetes; however, the physiological and molecular mechanisms for these
      benefits are not completely understood. Although endurance exercise has been
      shown to decrease lipogenesis, promote fatty acid oxidation (FAO), and increase
      mitochondrial biosynthesis in adipose tissue, muscle, and liver, its effects on
      intestinal lipid metabolism remain unknown. The absorptive cells of the small
      intestine, enterocytes, mediate the highly efficient absorption and processing of
      nutrients, including dietary fat for delivery throughout the body. We
      investigated how endurance exercise altered intestinal lipid metabolism in
      obesity and type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
      We assessed mRNA levels of genes associated with intestinal lipid metabolism in
      nonhyperphagic, sedentary Long-Evans Tokushima Otsuka (LETO) rats (L-Sed),
      hyperphagic, sedentary OLETF rats (O-Sed), and endurance exercised OLETF rats (O
      EndEx). O-Sed rats developed hyperphagia-induced obesity (HIO) and type 2
      diabetes compared with L-Sed rats. O-EndEx rats gained significantly less weight
      and fat pad mass, and had improved serum metabolic parameters without change in
      food consumption compared to O-Sed rats. Endurance exercise resulted in dramatic
      up-regulation of a number of genes in intestinal lipid metabolism and
      mitochondrial content compared with sedentary rats. Overall, this study provides
      evidence that endurance exercise programs intestinal lipid metabolism, likely
      contributing to its role in improving metabolic outcomes in obesity and type 2
      diabetes. 

PMID- 25602013
TI  - Recording, labeling, and transfection of single neurons in deep brain structures.
AB  - Genetic tools that permit functional or connectomic analysis of neuronal circuits
      are rapidly transforming neuroscience. The key to deployment of such tools is
      selective transfection of target neurons, but to date this has largely been
      achieved using transgenic animals or viral vectors that transduce subpopulations
      of cells chosen according to anatomical rather than functional criteria. Here, we
      combine single-cell transfection with conventional electrophysiological recording
      techniques, resulting in three novel protocols that can be used for reliable
      delivery of conventional dyes or genetic material in vitro and in vivo. We report
      that techniques based on single cell electroporation yield reproducible
      transfection in vitro, and offer a simple, rapid and reliable alternative to
      established dye-labeling techniques in vivo, but are incompatible with targeted
      transfection in deep brain structures. In contrast, we show that intracellular
      electrophoresis of plasmid DNA transfects brainstem neurons recorded up to 9 mm
      deep in the anesthetized rat. The protocols presented here require minimal, if
      any, modification to recording hardware, take seconds to deploy, and yield high
      recovery rates in vitro (dye labeling: 89%, plasmid transfection: 49%) and in
      vivo (dye labeling: 66%, plasmid transfection: 27%). They offer improved
      simplicity compared to the juxtacellular labeling technique and for the first
      time offer genetic manipulation of functionally characterized neurons in
      previously inaccessible brain regions. 

PMID- 25602014
TI  - Low glucose microenvironment of normal kidney cells stabilizes a subset of
      messengers involved in angiogenesis.
AB  - As glucose is a mandatory nutrient for cell proliferation and renewal, it is
      suspected that glucose microenvironment is sensed by all cell types to regulate
      angiogenesis. Several glucose-sensing components have been partially described to
      respond to high glucose levels. However, little is known about the response to
      low glucose. Here, we used well-differentiated isolated normal rat renal tubules
      under normal oxygenation conditions to assess the angiogenic response to low
      glucose. In apparent paradox, but confirming observations made separately in
      other models, high glucose but also low glucose increased mRNA level of vascular
      endothelial growth factor A (VEGFA). A subset of mRNAs including hypoxia
      inducible factor 1A (HIF1A), angiopoietin receptor (TIE-2), and VEGF receptor 2
      (FLK1) were similarly glucose-sensitive and responded to low glucose by increased
      stability independently of HIF1A and HIF2A proteins. These results contribute to
      gain some insights as to how normal cells response to low glucose may play a role
      in the tumor microenvironment. 

PMID- 25602015
TI  - Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia
      phenotypes.
AB  - Preeclampsia is a cardiovascular disorder of late pregnancy that is, commonly
      characterized by hypertension, renal structural damage and dysfunction, and fetal
      growth restriction. Prevailing etiologic models of this disorder include T-cell
      dysfunction as an initiating cause of preeclampsia. Indoleamine 2,3-dioxygenase
      (IDO), an enzyme that mediates the conversion of tryptophan to kynurenine, has
      been linked to preeclampsia in humans, and is known to regulate T-cell activity
      and an endothelial-derived relaxing factor. To test the hypothesis that IDO is
      causally involved in the pathogenesis of preeclampsia, mice deficient for IDO
      (IDO-KO) were generated on a C57BL/6 background. IDO-KO and wild-type C57BL/6
      mice were bred, and preeclampsia phenotypes were evaluated during pregnancy.
      Pregnant IDO-KO mice exhibited pathognomonic renal glomerular endotheliosis,
      proteinuria, pregnancy-specific endothelial dysfunction, intrauterine growth
      restriction, and mildly elevated blood pressure compared to wild-type mice.
      Together these findings highlight an important role for IDO in the generation of
      phenotypes typical of preeclampsia. Loss of IDO function may represent a risk
      factor for the development of preeclampsia. By extension, increased IDO activity,
      reductions in IDO reactants, or increases in IDO products may represent novel
      therapeutic approaches for this disorder. 

PMID- 25602016
TI  - Renal hemodynamics, function, and oxygenation during cardiac surgery performed on
      cardiopulmonary bypass: a modeling study.
AB  - Acute kidney injury, a prevalent complication of cardiac surgery performed on
      cardiopulmonary bypass (CPB), is thought to be driven partly by hypoxic damage in
      the renal medulla. To determine the causes of medullary hypoxia during CPB, we
      modeled its impact on renal hemodynamics and function, and thus oxygen delivery
      and consumption in the renal medulla. The model incorporates autoregulation of
      renal blood flow and glomerular filtration rate and the utilization of oxygen for
      tubular transport. The model predicts that renal medullary oxygen delivery and
      consumption are reduced by a similar magnitude during the hypothermic (down to 28
      degrees C) phase of CPB. Thus, the fractional extraction of oxygen in the
      medulla, an index of hypoxia, is increased only by 58% from baseline. However,
      during the rewarming phase (up to 37 degrees C), oxygen consumption by the
      medullary thick ascending limb increases 2.3-fold but medullary oxygen delivery
      increases only by 33%. Consequently, the fractional extraction of oxygen in the
      medulla is increased 2.7-fold from baseline. Thus, the renal medulla is
      particularly susceptible to hypoxia during the rewarming phase of CPB.
      Furthermore, autoregulation of both renal blood flow and glomerular filtration
      rate is blunted during CPB by the combined effects of hemodilution and
      nonpulsatile blood flow. Thus, renal hypoxia can be markedly exacerbated if
      arterial pressure falls below its target level of 50 mmHg. Our findings suggest
      that tight control of arterial pressure, and thus renal oxygen delivery, may be
      critical in the prevention of acute kidney injury associated with cardiac surgery
      performed on CPB. 

PMID- 25602017
TI  - Plasma irisin in runners and nonrunners: no favorable metabolic associations in
      humans.
AB  - Irisin is a hormone which mimics the favorable metabolic effects associated with
      regular exercise, by converting subcutaneous white fat into brownish fat, in
      rodents. Thirty-three human subjects (16 runners, 17 nonrunners) were measured
      for: resting energy expenditure (REE), body composition, VO2 Peak test,
      [irisin]p, and plasma metabolic profile. Nine female nonrunners then participated
      in a 10-week supervised 5 km training program and tested after the race. Two
      runners underwent (18)F-FDG-PET scans to quantify brown fat. No gender or age (28
      +/- 10 years) differences noted between matched cohorts. Runners averaged 58 +/-
      26 miles/week for 13 +/- 6 years and had lower bodyweight (63 vs. 88 kg; P <
      0.001), BMI (21 vs. 30 kg/m(2); P < 0.0001), triglycerides (58 vs. 123 mg/dL; P <
      0.01), total (white) fat (14 vs. 32%; P < 0.0001), and had higher VO2 Peak (63
      vs. 34 mL/kg-min; P < 0.0001) and HDL (65 vs. 48 mg/dL; P < 0.01) compared with
      nonrunners. [Irisin]p was lower in runners versus nonrunners both before (179 vs.
      197 ng/mL; NS) and after (207 vs. 226 ng/mL; NS) the VO2 Peak test. Significant
      (P < 0.05) positive correlations were noted between [irisin]p versus BMI (r(2) =
      0.15), triglycerides (r(2) = 0.40), and total body fat(g) (r(2) = 0.24) with a
      significant negative correlation between [irisin]p versus respiratory quotient
      (r(2) = 0.33). Total lean mass significantly correlated with REE (r(2) = 0.58)
      while total fat mass inversely correlated with VO2 Peak (r(2) = 0.64). Nonrunners
      had lower [irisin]p after completion of the training program (194 vs.181 ng/mL;
      pre- to post-training; P > 0.05). Neither runner selected for (18)F-FDG-PET scans
      had brown fat. Runners demonstrated significantly healthier metabolic and body
      composition profiles compared with nonrunners. None of these favorable exercise
      effects were positively associated with [irisin]p.. 

PMID- 25602018
TI  - Histopathological, biomechanical, and behavioral pain findings of Achilles
      tendinopathy using an animal model of overuse injury.
AB  - Animal models of forced running are used to study overuse tendinopathy, a common
      health problem for which clear evidence for effective and accessible treatments
      is still lacking. In these models, pain evaluation is necessary to better
      understand the disease, help design and evaluate therapies, and ensure humane
      treatment of the animals. Therefore, the main objective of this study was to
      evaluate pain and pathologic findings in an animal model of moderate Achilles
      tendinopathy induced by treadmill running. Air puffs, instead of electrical
      shocks, were used to stimulate running so that pain associated with stimulation
      would be avoided. Pressure pain sensitivity was evaluated in vivo using a new
      instrumented plier, whereas spinal cord peptides were analyzed ex vivo with high
      performance liquid chromatography tandem mass spectrometry. Tendon histologic
      slides were semiquantitatively evaluated, using the Bonar score technique and
      biomechanical properties, using the traction test. After 8 weeks of treadmill
      running (2 weeks for adaptation and 6 weeks for the lesion protocol), the
      protocol was stopped because the air puffs became ineffective to stimulate
      running. We, nevertheless, observed some histologic changes characteristic of
      overuse tendinopathy as well as decreased mechanical properties, increased
      Substance P and dynorphin A peptides but without pressure pain sensitivity. These
      results suggest that air-puffs stimulation is sufficient to induce an early stage
      tendinopathy to study new therapeutic drugs without inducing unnecessary pain.
      They also indicate that pain-associated peptides could be related with movement
      evoked pain and with the sharp breakdown of the running performance. 

PMID- 25602019
TI  - Expression of pigment epithelium-derived factor and thrombospondin-1 regulate
      proliferation and migration of retinal pigment epithelial cells.
AB  - Age-related macular degeneration (AMD) is the leading cause of vision loss among
      elderly. Although the pathogenesis of AMD is associated with retinal pigmented
      epithelium (RPE) dysfunction and abnormal neovascularization the detailed
      mechanisms remain unresolved. RPE is a specialized monolayer of epithelial cells
      with important functions in ocular homeostasis. Pathological RPE damage
      contributes to major ocular conditions including retinal degeneration and
      irreversible loss of vision in AMD. RPE cells also assist in the maintenance of
      the ocular angiogenic balance by production of positive and negative regulatory
      factors including vascular endothelial growth factor (VEGF), thrombospondin-1
      (TSP1), and pigment epithelium-derived factor (PEDF). The altered production of
      PEDF and TSP1, as endogenous inhibitors of angiogenesis and inflammation, by RPE
      cells have been linked to pathogenesis of AMD and choroidal and retinal
      neovascularization. However, lack of simple methods for isolation and culture of
      mouse RPE cells has resulted in limited knowledge regarding the cell autonomous
      role of TSP1 and PEDF in RPE cell function. Here, we describe a method for
      routine isolation and propagation of RPE cells from wild-type, TSP1, and PEDF
      deficient mice, and have investigated their impact on RPE cell function. We
      showed that expression of TSP1 and PEDF significantly impacted RPE cell
      proliferation, migration, adhesion, oxidative state, and phagocytic activity with
      minimal effect on their basal rate of apoptosis. Together, our results indicated
      that the expression of PEDF and TSP1 by RPE cells play crucial roles not only in
      regulation of ocular vascular homeostasis but also have significant impact on
      their cellular function. 

PMID- 25602020
TI  - Effects of systemic hypoxia on human muscular adaptations to resistance exercise
      training.

PMID- 25602021
TI  - Suppressed autophagy flux in skeletal muscle of an amyotrophic lateral sclerosis
      mouse model during disease progression.
AB  - Accumulation of abnormal protein inclusions is implicated in motor neuron
      degeneration in amyotrophic lateral sclerosis (ALS). Autophagy, an intracellular
      process targeting misfolded proteins and damaged organelles for lysosomal
      degradation, plays crucial roles in survival and diseased conditions. Efforts
      were made to understand the role of autophagy in motor neuron degeneration and to
      target autophagy in motor neuron for ALS treatment. However, results were quite
      contradictory. Possible autophagy defects in other cell types may also complicate
      the results. Here, we examined autophagy activity in skeletal muscle of an ALS
      mouse model G93A. Through overexpression of a fluorescent protein LC3-RFP, we
      found a basal increase in autophagosome formation in G93A muscle during disease
      progression when the mice were on a regular diet. As expected, an autophagy
      induction procedure (starvation plus colchicine) enhanced autophagy flux in
      skeletal muscle of normal mice. However, in response to the same autophagy
      induction procedure, G93A muscle showed significant reduction in the autophagy
      flux. Immunoblot analysis revealed that increased cleaved caspase-3 associated
      with apoptosis was linked to the cleavage of several key proteins involved in
      autophagy, including Beclin-1, which is an essential molecule connecting
      autophagy and apoptosis pathways. Taking together, we provide the evidence that
      the cytoprotective autophagy pathway is suppressed in G93A skeletal muscle and
      this suppression may link to the enhanced apoptosis during ALS progression. The
      abnormal autophagy activity in skeletal muscle likely contributes muscle
      degeneration and disease progression in ALS. 

PMID- 25602022
TI  - Differentiating peer and friend social information-processing effects on stress
      and glycemic control among youth with type 1 diabetes.
AB  - OBJECTIVE: Many adolescents with Type 1 diabetes (T1D) find adherence difficult
      in social situations because they fear negative evaluations by others. These
      negative reaction attributions are associated with anticipated adherence
      difficulties, stress, and glycemic control. It is unclear whether peer versus
      friend attributions are distinct constructs, or whether there is a differential
      impact on glycemic control moderated by youth characteristics. METHOD: Youth with
      T1D (n = 142; 58% female; 84% Caucasian, mean = 13.79 years, standard deviation =
      2.10) completed the Peer Attribution and Diabetes Stress Questionnaires. HbA1cs
      were obtained from medical records. RESULTS: Negative peer versus friend
      attributions appear distinct and were differentially related to anticipated
      adherence difficulties, stress, and glycemic control, with peer attributions
      having the strongest effect. Grade, age, and sex were not moderators for these
      relationships. CONCLUSION: Peer-related attributions may be a particularly
      salient target for interventions to improve adherence and distress among youth
      with T1D.

PMID- 25602023
TI  - The second European evidenced-based consensus on reproduction and pregnancy in
      inflammatory bowel disease.
AB  - Trying to conceive and being pregnant is an emotional period for those involved.
      In the majority of patients suffering from inflammatory bowel disease,
      maintenance therapy is required during pregnancy to control the disease, and
      disease control might necessitate introduction of new drugs during a vulnerable
      period. In this updated consensus on the reproduction and pregnancy in
      inflammatory bowel disease reproductive issues including fertility, the safety of
      drugs during pregnancy and lactation are discussed.

PMID- 25602024
TI  - Long-term clinical outcomes of urban versus rural environment in Korean patients
      with Crohn's disease: results from the CONNECT study.
AB  - BACKGROUND AIMS: Environmental factors and genetic predisposition are thought to
      play important roles in the pathogenesis of Crohn's disease [CD]. Although
      numerous studies have reported the positive association between urban environment
      and CD development, few studies have compared the clinical outcomes between urban
      and rural environments. Therefore, this study aimed to compare the clinical
      characteristics and long-term prognosis between urban and rural populations of
      patients with CD. METHODS: This retrospective multicenter cohort study included
      1002 Korean patients diagnosed with CD [743 urban residents and 259 rural
      residents] between 1982 and 2008 from 32 medical centers. The clinical outcomes
      of urban versus rural populations were compared using the KaplanMeier method and
      log-rank test. RESULTS: Disease distribution and behavior of the urban population
      did not differ from those of the rural population. There were no significant
      differences in the cumulative probabilities of perianal fistula [P = 0.086] and
      intestinal complications such as stricture [P = 0.109], fistula [P = 0.952],
      abscess [P = 0.227], and perforation [P = 0.382] between the two groups. In
      addition, no significant differences were observed between the two groups with
      regard to the cumulative probabilities of immunosuppressant use [P = 0.527] and
      biologic agent use [P = 0.731]. Although the cumulative probability of surgery in
      the urban population was significantly higher than that in the rural population
      [P = 0.040], this difference was mainly established within the first year from
      diagnosis [19.1% vs 13.5%, P = 0.042] and observed only among patients diagnosed
      in 2005-2008 [P = 0.033]. CONCLUSIONS: There were no differences in terms of
      disease presentation and natural history between urban and rural populations,
      except for a higher rate of surgery in the urban population who were recently
      diagnosed with CD.

PMID- 25602026
TI  - Productive performance of brown-egg laying pullets from hatching to 5 weeks of
      age as affected by fiber inclusion, feed form, and energy concentration of the
      diet.
AB  - The effects of fiber inclusion, feed form, and energy concentration of the diet
      on the growth performance of pullets from hatching to 5 wk age were studied in 2
      experiments. In Experiment 1, there was a control diet based on cereals and
      soybean meal, and 6 extra diets that included 2 or 4% of cereal straw, sugar beet
      pulp (SBP), or sunflower hulls (SFHs) at the expense (wt/wt) of the whole control
      diet. From hatching to 5 wk age fiber inclusion increased (P<0.05) ADG and ADFI,
      and improved (P<0.05) energy efficiency (EnE; kcal AMEn/g ADG), but body weight
      (BW) uniformity was not affected. Pullets fed SFH tended to have higher ADG than
      pullets fed SBP (P=0.072) with pullets fed straw being intermediate. The feed
      conversion ratio (FCR) was better (P<0.05) with 2% than with 4% fiber inclusion.
      In Experiment 2, 10 diets were arranged as a 2*5 factorial with 2 feed forms
      (mash vs. crumbles) and 5 levels of AMEn (2,850, 2,900, 2,950, 3,000, and 3,050
      kcal/kg). Pullets fed crumbles were heavier and had better FCR than pullets fed
      mash (P<0.001). An increase in the energy content of the crumble diets reduced
      ADFI and improved FCR linearly, but no effects were detected with the mash diets
      (P<0.01 and P<0.05 for the interactions). Feeding crumbles tended to improve BW
      uniformity at 5 wk age (P=0.077) but no effects were detected with increases in
      energy concentration of the diet. In summary, the inclusion of moderate amounts
      of fiber in the diet improves pullet performance from hatching to 5 wk age. The
      response of pullets to increases in energy content of the diet depends on feed
      form with a decrease in feed intake when fed crumbles but no changes when fed
      mash. Feeding crumbles might be preferred to feeding mash in pullets from
      hatching to 5 wk age.

PMID- 25602025
TI  - Alcohol consumption and risk of heart failure: the Atherosclerosis Risk in
      Communities Study.
AB  - AIM: Alcohol is a known cardiac toxin and heavy consumption can lead to heart
      failure (HF). However, the relationship between moderate alcohol consumption and
      risk for HF, in either men or women, remains unclear. METHODS AND RESULTS: We
      examined 14 629 participants of the Atherosclerosis Risk in Communities (ARIC)
      study (54 +/- 6 years, 55% women) without prevalent HF at baseline (1987-89) who
      were followed for 24 +/- 1 years. Self-reported alcohol consumption was assessed
      as the number of drinks/week (1 drink = 14 g of alcohol) at baseline, and updated
      cumulative average alcohol intake was calculated over 8.9 +/- 0.3 years. Using
      multivariable Cox proportional hazards models, we examined the relation of
      alcohol intake with incident HF and assessed whether associations were modified
      by sex. Overall, most participants were abstainers (42%) or former drinkers
      (19%), with 25% reporting up to 7 drinks per week, 8% reporting >=7 to 14 drinks
      per week, and 3% reporting >=14-21 and >=21 drinks per week, respectively.
      Incident HF occurred in 1271 men and 1237 women. Men consuming up to 7
      drinks/week had reduced risk of HF relative to abstainers (hazard ratio, HR 0.80,
      95% CI 0.68-0.94, P = 0.006); this effect was less robust in women (HR 0.84, 95%
      CI 0.71-1.00, P = 0.05). In the higher drinking categories, the risk of HF was
      not significantly different from abstainers, either in men or in women.
      CONCLUSION: In the community, alcohol consumption of up to 7 drinks/week at early
      middle age is associated with lower risk for future HF, with a similar but less
      definite association in women than in men. These findings suggest that despite
      the dangers of heavy drinking, modest alcohol consumption in early-middle age may
      be associated with a lower risk for HF.

PMID- 25602027
TI  - Assessing patient safety competencies using Objective Structured Clinical Exams:
      a new twist on an old tool.

PMID- 25602028
TI  - Lack of fructose 2,6-bisphosphate compromises photosynthesis and growth in
      Arabidopsis in fluctuating environments.
AB  - The balance between carbon assimilation, storage and utilisation during
      photosynthesis is dependent on partitioning of photoassimilate between starch and
      sucrose, and varies in response to changes in the environment. However, the
      extent to which the capacity to modulate carbon partitioning rapidly through
      short-term allosteric regulation may contribute to plant performance is unknown.
      Here we examine the physiological role of fructose 2,6-bisphosphate (Fru-2,6-P2 )
      during photosynthesis, growth and reproduction in Arabidopsis thaliana (L.). In
      leaves this signal metabolite contributes to coordination of carbon assimilation
      and partitioning during photosynthesis by allosterically modulating the activity
      of cytosolic fructose-1,6-bisphosphatase. Three independent T-DNA insertional
      mutant lines deficient in 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
      (F2KP), the bifunctional enzyme responsible for both the synthesis and
      degradation of Fru-2,6-P2 , lack Fru-2,6-P2 . These plants have normal steady
      state rates of photosynthesis, but exhibit increased partitioning of
      photoassimilate into sucrose and have delayed photosynthetic induction kinetics.
      The F2KP-deficient plants grow normally in constant environments, but show
      reduced growth and seed yields relative to wildtype plants in fluctuating light
      and/or temperature. We conclude that Fru-2,6-P2 is required for optimum
      regulation of photosynthetic carbon metabolism under variable growth conditions.
      These analyses suggest that the capacity of Fru-2,6-P2 to modulate partitioning
      of photoassimilate is an important determinant of growth and fitness in natural
      environments. 

PMID- 25602029
TI  - A tonoplast Glu/Asp/GABA exchanger that affects tomato fruit amino acid
      composition.
AB  - Vacuolar accumulation of acidic metabolites is an important aspect of tomato
      fruit flavour and nutritional quality. The amino acids Asp and Glu accumulate to
      high concentrations during ripening, while gamma-aminobutyrate (GABA) shows an
      approximately stoichiometric decline. Given that GABA can be catabolised to form
      Glu and subsequently Asp, and the requirement for the fruit to maintain osmotic
      homeostasis during ripening, we hypothesised the existence of a tonoplast
      transporter that exports GABA from the vacuole in exchange for import of either
      Asp or Glu. We show here that the tomato vacuolar membrane possesses such a
      transport property: transport of Glu across isolated tonoplast vesicle membranes
      was trans-stimulated in counterexchange mode by GABA, Glu and Asp. We identified
      SlCAT9 as a candidate protein for this exchanger using quantitative proteomics of
      a tonoplast-enriched membrane fraction. Transient expression of a SlCAT9-YFP
      fusion in tobacco confirmed a tonoplast localisation. The function of the protein
      was examined by overexpression of SlCAT9 in transgenic tomato plants. Tonoplast
      vesicles isolated from transgenic plants showed higher rates of Glu and GABA
      transport than wild-type (WT) only when assayed in counterexchange mode with Glu,
      Asp, or GABA. Moreover, there were substantial increases in the content of all
      three cognate amino acids in ripe fruit from the transgenic plants. We conclude
      that SlCAT9 is a tonoplast Glu/Asp/GABA exchanger that strongly influences the
      accumulation of these amino acids during fruit development. 

PMID- 25602030
TI  - Do we have predictors of therapy responsiveness for a multimodal therapy concept
      and aerobic training in breast cancer survivors with chronic cancer-related
      fatigue?
AB  - Cancer-related fatigue (CRF) is a burdensome symptom for breast cancer (BC)
      patients. In this pilot study, we tested several questionnaires as predictors for
      treatment responsiveness, along with the implementation of a multimodal therapy
      concept consisting of sleep, psycho-education, eurythmy, painting therapy and
      standard aerobic training. At the Community Hospital Havelhohe and the Hannover
      Medical School, 31 BC patients suffering from CRF could be evaluated in a 10-week
      intervention study. CRF was assessed by the Cancer Fatigue Scale (CFS-D). Further
      questionnaires were the Pittsburgh Sleep Quality Index, the autonomic regulation
      scale, Self-Regulation Scale (SRS), the Internal Coherence Scale (ICS) and the
      European Organization of Research and Treatment Health-Related Quality of Life
      Core Questionnaire scale. We estimated the regression coefficients of all scales
      on CFS-D by simple and multiple linear regression analyses and compared
      regression slopes and variances between the different questionnaires on CFS-D at
      the end of treatment. We found a significant impact of SRS and ICS at baseline on
      CFS-D at the end of the intervention [absolute standardised multiple regression
      coefficient values ranging from 0.319 (SRS) to 0.269 (ICS)] but not for the other
      questionnaires. In conclusion, this study supports the hypothesis that the SRS or
      ICS measuring adaptive capacities could be more appropriate as outcome predictors
      than classical questionnaire measures in complex interventions studies. 

PMID- 25602031
TI  - Why are marine adaptive radiations rare in Hawai'i?
AB  - Islands can be sites of dynamic evolutionary radiations, and the Hawaiian Islands
      have certainly given us a bounty of insights into the processes and mechanisms of
      diversification. Adaptive radiations in silverswords and honeycreepers have
      inspired a generation of biologists with evidence of rapid diversification that
      resulted in exceptional levels of ecological and morphological diversity. In this
      issue of Molecular Ecology, tiny waterfall-climbing gobies make a case for their
      place among Hawaiian evolutionary elite. Moody et al. (2015) present an analysis
      of gene flow and local adaptation in six goby populations on Kaua'i and Hawai'i
      measured in three consecutive years to try to disentangle the relative role of
      local adaptation and gene flow in shaping diversity within Sicyopterus stimpsoni.
      Their study shows that strong patterns of local selection result in streams with
      gobies adapted to local conditions in spite of high rates of gene flow between
      stream populations and no evidence for significant genetic population structure.
      These results help us understand how local adaptation and gene flow are balanced
      in gobies, but these fishes also offer themselves as a model that illustrates why
      adaptive diversification in Hawai'i's marine fauna is so different from the
      terrestrial fauna.

PMID- 25602033
TI  - Involvement of TLR7 and TLR8 in conceptus development and establishment of
      pregnancy in sheep.
AB  - Toll-like receptors (TLRs) belong to the innate immune system and regulate
      inflammatory events that affect mammalian reproduction. In Study 1, we
      demonstrated that abundance of ovine TLR1-TLR9 mRNAs in the uterus differs due to
      reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle
      and pregnancy (TLR1-TLR3, TLR5-TLR7, and TLR9). Expression of TLR7 and TLR8
      proteins was localized primarily to uterine epithelia and stroma and regulated in
      a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7
      and TLR8 on all days studied and that expression of the envelope protein of ovine
      endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day
      13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were
      conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected
      into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually
      and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO
      treated conceptuses were developmentally retarded, produced less interferon tau
      (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls.
      Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than
      that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8
      conceptuses. Results of this study indicated differences in TLR1-TLR9 expression
      due to reproductive status and the day of the estrous cycle and pregnancy. TLR7
      and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and
      formation of BNCs by conceptuses. These findings corroborate our hypothesis that
      TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation
      events in conceptus development and differentiated functions of trophectoderm
      cells. 

PMID- 25602035
TI  - Regulation of the ovarian oxidative status by leptin during the ovulatory process
      in rats.
AB  - Leptin exerts both stimulatory and inhibitory effects on the ovulatory process.
      In this study, we investigated whether these opposite effects involve changes in
      the oxidative status in response to different levels of leptin. To this end, we
      performed both in vivo and in vitro assays using ovaries of immature rats primed
      with gonadotropins to induce ovulation. Superoxide dismutase (SOD) and catalase
      (CAT) activity, lipid peroxidation, glutathione (GSH) content, and reactive
      oxygen species (ROS) were studied as oxidative damage-related parameters. The
      expression of BCL2, BAX, and caspase 3 were measured by western blot as apoptosis
      related biomarkers. The acute treatment with leptin, which inhibits ovulation,
      decreased SOD activity and increased active caspase 3 expression. No differences
      were found in CAT activity, lipid peroxidation, or total GSH. In contrast, the
      daily administration of leptin, which induces ovulation, decreased GSH content,
      ROS levels, and Bax and active caspase 3 expression, but caused no changes in
      other parameters. In addition, the daily administration of leptin induced
      follicular growth, measured by the number of antral follicles in ovarian
      sections. Using ovarian explant cultures, we found increased BCL2 expression and
      decreased SOD activity at low and high concentrations of leptin respectively.
      Thus, leptin can modulate the oxidative status of the ovarian tissue, during the
      ovulatory process, by acting on different targets according to its circulating
      levels. At low concentration, leptin seems to play a protective role against the
      oxidative stress, whereas at high concentrations, this protein seems to be
      involved in cell death. 

PMID- 25602034
TI  - Murine binder of sperm protein homolog 1: a new player in HDL-induced
      capacitation.
AB  - Binder of sperm (BSP) proteins are ubiquitous among mammals and are exclusively
      expressed in male genital tract. The main function associated with BSP proteins
      is their ability to promote sperm capacitation. In mice, two proteins (BSP
      protein homolog 1 (BSPH1) and BSPH2) have been studied. Using recombinant
      strategies, BSPH1 was found to bind to epididymal sperm membranes and promote
      sperm capacitation in vitro. The goal of this study was to evaluate the role of
      native murine BSPH1 protein in sperm capacitation induced by BSA and HDLs. The
      effect of antibodies, antigen-binding fragments (Fabs), and F(ab')2 specific for
      murine BSPH1 on BSA- and HDL-induced capacitation was tested. Results indicate
      that BSPH1 has no direct role in BSA-induced capacitation. However, antibodies,
      Fabs, and F(ab')(2) could block capacitation induced by HDLs and could inhibit
      the HDL-induced increase in tyrosine phosphorylation, suggesting a specific
      interaction between HDLs and BSPH1. Results indicate that murine BSPH1 proteins
      in mice could be a new important piece of the puzzle in sperm capacitation
      induced by HDLs. As murine BSPH1 is orthologous to human BSPH1, this study could
      also lead to new insights into the functions and the importance of the human
      protein in male fertility.

PMID- 25602036
TI  - Anakinra and etanercept prevent embryo loss in pregnant nonobese diabetic mice.
AB  - Bacteria and viruses activate the host innate immune response via Toll-like
      receptor (TLR)-involved signaling and potentially cause pregnancy failure. TLR7
      and TLR9 respond to single-stranded RNA (a viral intermediate) and hypomethylated
      CpG DNA motifs (specific molecular constituents of bacteria) respectively. In
      this study, we treated murine RAW264.7 cells with R837, CpG1826, or a combination
      of the two. RT-PCR was performed to detect cytokines, Tlr7, and Tlr9. WT and
      nonobese diabetic murine embryo resorption models were established by i.p.
      injections of TLR7 and TLR9 ligands. Neutralizing antibodies and the IL1beta and
      TNFalpha inhibitors were used. The specific inhibitors anakinra and etanercept
      effectively prevented TLR7 and TLR9 ligand-induced embryo loss. Notably, this
      effect was not observed in decidual NK cell-depleted mice. Our findings suggest
      that anakinra and etanercept may have potential for preventing TLR7 or TLR9
      ligand-induced abortion in the presence of decidual NK cells. 

PMID- 25602032
TI  - Evolutionary and biogeographical patterns of barnacles from deep-sea hydrothermal
      vents.
AB  - The characterization of evolutionary and biogeographical patterns is of
      fundamental importance to identify factors driving biodiversity. Due to their
      widespread but discontinuous distribution, deep-sea hydrothermal vent barnacles
      represent an excellent model for testing biogeographical hypotheses regarding the
      origin, dispersal and diversity of modern vent fauna. Here, we characterize the
      global genetic diversity of vent barnacles to infer their time of radiation,
      place of origin, mode of dispersal and diversification. Our approach was to
      target a suite of multiple loci in samples representing seven of the eight
      described genera. We also performed restriction-site associated DNA sequencing on
      individuals from each species. Phylogenetic inferences and topology hypothesis
      tests indicate that vent barnacles have colonized deep-sea hydrothermal vents at
      least twice in history. Consistent with preliminary estimates, we find a likely
      radiation of barnacles in vent ecosystems during the Cenozoic. Our analyses
      suggest that the western Pacific was the place of origin of the major vent
      barnacle lineage, followed by circumglobal colonization eastwards through the
      Southern Hemisphere during the Neogene. The inferred time of radiation rejects
      the classic hypotheses of antiquity of vent taxa. The timing and the mode of
      origin, radiation and dispersal are consistent with recent inferences made for
      other deep-sea taxa, including nonvent species, and are correlated with the
      occurrence of major geological events and mass extinctions. Thus, we suggest that
      the geological processes and dispersal mechanisms discussed here can explain the
      current distribution patterns of many other marine taxa and have played an
      important role shaping deep-sea faunal diversity. These results also constitute
      the critical baseline data with which to assess potential effects of
      anthropogenic disturbances on deep-sea ecosystems. 

PMID- 25602038
TI  - Transition of China's drug policy: problems in practice.

PMID- 25602039
TI  - Neuroimaging of cigarette cravings: individual differences matter: commentary.

PMID- 25602037
TI  - Contrasting definitive hosts as determinants of the genetic structure in a
      parasite with complex life cycle along the south-eastern Pacific.
AB  - The spatial genetic structure (and gene flow) of parasites with complex life
      cycles, such as digeneans, has been attributed mainly to the dispersion ability
      of the most mobile host, which most often corresponds to the definitive host
      (DH). In this study, we compared the genetic structure and diversity of adult
      Neolebouria georgenascimentoi in two fish species (DHs) that are extensively
      distributed along the south-eastern Pacific (SEP). The analysis was based on the
      cytochrome oxidase subunit I gene sequences of parasites collected between 23
      degrees S and 45 degrees S. In total, 202 sequences of N. georgenascimentoi in
      Pinguipes chilensis isolated from nine sites and 136 sequences of Prolatilus
      jugularis from five sites were analysed. Our results showed that N.
      georgenascimentoi is a species complex that includes three different parasite
      species; however, in this study, only lineage 1 and 2 found in P. chilensis and
      P. jugularis, respectively, were studied because they are widely distributed
      along the coastline. Lineage 1 parasites had two common haplotypes with wide
      distribution and unique haplotypes in northern sites. Lineage 2 had only one
      common haplotype with wide distribution and a large number of unique haplotypes
      with greater genetic diversity. Both lineages have experienced recent population
      expansion. Only lineage 1 exhibited a genetic structure that was mainly
      associated with a biogeographical break at approximately 30 degrees S along the
      SEP. Our finding suggests that host access to different prey (=intermediate
      hosts) could affect the genetic structure of the parasite complex discovered
      here. Consequently, difference between these patterns suggests that factors other
      than DH dispersal are involved in the genetic structure of autogenic parasites. 

PMID- 25602040
TI  - Multiple ambiguities in the measurement of drug craving.

PMID- 25602041
TI  - Importance of construct validity in functional neuroimaging of craving.

PMID- 25602042
TI  - All cravings are not created equal.

PMID- 25602043
TI  - Commentary on Degenhardt et al (2015): a new formulation for research.

PMID- 25602044
TI  - Commentary on Salom et al. (2015): Examining the developmental underpinnings of
      comorbid mental health and substance use outcomes in young adults.

PMID- 25602045
TI  - Commentary on Pennay et al. (2015): Measuring the effects of alcohol mixed with
      energy drinks on intoxication with real-world data.

PMID- 25602046
TI  - Synthetic growth hormone releasers detected in seized drugs: new trends in the
      use of drugs for performance enhancement.

PMID- 25602047
TI  - New alcohol policies appear to have reduced traffic casualties in Chile.

PMID- 25602049
TI  - A rare cardiac haemangioma in the right ventricle diagnosed accurately using 18F
      fluorodeoxyglucose-positron emission tomography.
AB  - A right ventricular cardiac tumour was incidentally detected in a 61-year-old man
      during a preoperative examination for coronary artery bypass grafting (CABG).
      Findings on computed tomography and magnetic resonance imaging suggested the
      differential diagnoses of myxoma, haemangioma and haemangiosarcoma, and it was
      difficult to identify whether the tumour was benign or malignant. (18)F
      fluorodeoxyglucose-positron emission tomography strongly suggested a benign
      tumour. We enucleated the tumour, because an intraoperative frozen section also
      strongly suggested a benign origin. After resection, CABG under cardiopulmonary
      bypass was performed. Histopathological and immunohistochemical analysis
      indicated a cavernous haemangioma without evidence of malignant tissue. The
      patient has survived 20 months after surgery with no evidence of tumour
      recurrence. 

PMID- 25602050
TI  - Preservation of the subvalvular apparatus during mitral valve replacement of
      rheumatic valves does not affect long-term survival.
AB  - OBJECTIVES: The importance of preservation of the subvalvular apparatus (PSVA)
      during mitral valve replacement (MVR) in non-rheumatic mitral valves is well
      recognized. Our aim was to analyse the impact of PSVA in MVR for rheumatic valves
      on long-term survival. METHODS: From January 1992 to December 2012, 605
      consecutive patients with rheumatic mitral valve disease were submitted to MVR.
      PSVA (limited to the posterior leaflet) was achieved in 224 (37.7%) patients.
      Follow-up was 4259 patient-years, and complete for 97% of the patients.
      Propensity score analysis was introduced to reduce selection bias. RESULTS:
      Patients with PSVA were slightly older (61.9 vs 59.8 years, P = 0.014), with
      lower incidence of calcification (54.9 vs 63.0%, P = 0.05), pure mitral stenosis
      (29.9 vs 38.9%, P = 0.014) and history of rheumatic fever (44.6 vs 53.9%, P =
      0.028). Mechanical prostheses were more frequently implanted in the Non-PSVA
      group (75.1 vs 65.6%, P = 0.013). Thirty-day mortality was 1.1%. Late survival
      rates at 5, 10 and 18 years were 86.6 +/- 2.0, 70.8 +/- 3.2 and 48.0 +/- 5.1%,
      respectively, with no difference between groups. Both groups had compromised late
      survival when compared with the general population (age and gender matched, P <
      0.001). Only age, large left atrium, pulmonary hypertension and 'pure' MR
      appeared as independent predictors for late mortality. There was no difference
      regarding adverse valve-related events between groups. CONCLUSIONS: Patients
      submitted to MVR for rheumatic mitral valve disease have a poor prognosis,
      independently of having the subvalvular apparatus preserved. PSVA did not improve
      late survival in this setting.

PMID- 25602051
TI  - The effect of haemostatic devices on bone healing 6 months postoperatively in
      sternotomized pigs.
AB  - OBJECTIVES: Bone wax is frequently used to diminish bleeding after sternotomy.
      Water-soluble polymer wax has been shown to diminish postoperative bleeding and,
      unlike traditional bone wax, to be absorbed and removed by the organism in an
      unchanged state. We have previously shown that bone wax impairs early bone
      healing after sternotomy, whereas polymer wax does not. This difference was
      observed 6 weeks postoperatively and questions arose as to whether these effects
      were long term. Therefore, we hypothesized that bone wax impairs bone healing in
      sternotomized pigs 6 months postoperatively, whereas polymer wax does not.
      METHODS: Fourteen Landrace/Yorkshire pigs were sternotomized and then randomly
      assigned to haemostasis by either bone wax (WAX-group) or water-soluble polymer
      wax (POL-group). After 6 months, the pigs were euthanized and the sternum was
      removed and prepared for further assessment. Bone fracture strength and bone
      stiffness were determined using a modified three-point bending test, whereas bone
      healing was examined by means of quantitative histology. Six pigs died before the
      end of the study due to failure to thrive, valve prosthesis endocarditis and
      coronary artery occlusion. RESULTS: The mechanical testing showed no difference
      between groups with regard to fracture strength [WAX-group versus POL-group;
      214.8 (85.5-478.5) vs 203.8 (90.4-478.5) N, P = 0.986] or maximum stiffness
      [213.0 (81.5-409.5) vs 348.5 (23.3-689.5) N/mm, P = 0.128]. Histology showed
      predominance of fibroblast-covered surfaces [10.6% (1.8-23.3%) vs 4.1% (0.0
      13.0%), P < 0.001] and fibrous tissue volume [45.4% (6.9-82.0%) vs 17.4% (2.9
      55.0%), P < 0.001] in animals treated with bone wax. The volume fraction of
      calcified bone tended to be higher in the POL-group [26.8% (4.3-35.8%) vs 16.7%
      (1.5-35.8%), P = 0.065]. Granulomas comprised 12.5% (0.0-78.9%) of the volume
      fraction in the WAX-group compared with 0.0% (0.0-0.0%) in the POL-group (P <
      0.001). CONCLUSION: Bone wax and water-soluble polymer wax had similar long-term
      effects on bone mechanical properties. Histology confirmed our hypothesis and
      showed a more extensive foreign body reaction in animals treated with bone wax
      than in those treated with water-soluble polymer wax.

PMID- 25602052
TI  - New-onset atrial fibrillation at discharge in patients after coronary artery
      bypass surgery: short- and long-term morbidity and mortality.
AB  - OBJECTIVES: Atrial fibrillation (AF) after coronary artery bypass surgery is
      often considered a non-harmful and self-terminating condition. We studied the
      mortality and morbidity in patients with new-onset AF (NOAF) present at the time
      of hospital discharge. METHODS: We conducted a retrospective follow-up study of
      138 patients discharged in NOAF (NOAF group) and a propensity score-matched
      control group of 138 patients who were in sinus rhythm (SR) at the time of
      discharge (SR group). Follow-up data were obtained from the hospitals' records,
      from the national registry of hospital discharge diagnoses and death records from
      the Finnish Statistical Bureau. RESULTS: At 3 and 12 months after surgery, AF was
      present in 20.3 and 23.2% of patients in the NOAF group, respectively, but in
      none of the patients in the SR group (P < 0.001). At the end of follow-up (8.5 +/
      2.8 years), 28.3 and 5.1% of the patients who survived in the NOAF and SR
      groups, respectively, were in chronic AF (P < 0.001). All-cause mortality (33.3
      vs 18.8%, P = 0.002) and cardiac mortality (15.2 vs 4.3%, P = 0.001) were higher
      in the NOAF group when compared with the SR group. The incidence of
      cerebrovascular disorders in the NOAF and SR groups did not differ from each
      other (13.8 vs 10.9%, P = NS). Independent risk factors for all-cause death were
      NOAF [P = 0.024, hazard ratio (HR) 1.828, 95% CI 0.547-3.09], age (P = 0.0025, HR
      1.074, 95% CI 1.026-1.13), diabetes (P = 0.015, HR 1.965, 95% CI 1.142-3.38) and
      prolonged respiratory support (P = 0.00024, HR 3.394, 95% CI 1.767-6.52). In
      addition, patients in the NOAF group had more hospitalizations due to heart
      failure (7.2 vs 0.7%, P < 0.001) and had a higher rate of implantation of
      permanent pacemakers (6.5 vs 0.4%, P < 0.001). CONCLUSIONS: A majority of NOAF
      patients revert to SR during the first months after surgery. On the other hand,
      20-25% of NOAF patients develop chronic AF during long-term follow-up. Almost
      half of the NOAF patients were hospitalized during follow-up due to
      cardiovascular causes. Similarly, NOAF was associated with increased mortality
      due to cardiac causes, but not increased risk of stroke. This highlights the need
      for proper oral anticoagulation therapy in these patients.

PMID- 25602053
TI  - New-onset atrial fibrillation following coronary bypass surgery predicts long
      term mortality: a systematic review and meta-analysis.
AB  - Atrial fibrillation (AF) is one of the most common postoperative complications
      following cardiac surgery. Recent evidence suggests that postoperative atrial
      fibrillation (POAF) may be more 'malignant' than previously thought, associated
      with follow-up mortality and morbidity. To evaluate the long-term survival of
      POAF versus No-POAF cohorts following coronary bypass surgery, the current meta
      analysis with reconstructed individual patient data was performed. Electronic
      searches were performed using six databases from their inception to August 2014.
      Relevant studies with long-term survival data presented for POAF versus No-POAF
      were identified. Data were extracted by two independent reviewers and analysed
      according to predefined clinical endpoints. The pooled hazard ratio (HR)
      significantly favoured higher survival in No-POAF over POAF (HR 1.28; 95% CI,
      1.19-1.37; I(2) = 96%; P < 0.00001). Individual patient data of 69 518 patients
      were available for inverted Kaplan-Meier survival curve analysis. Analysis of
      aggregate data using Kaplan-Meier curve methods for POAF versus No-POAF groups
      determined survival rates at the 1-year (95.7 vs 98%), 2-year (92.3 vs 95.4%), 3
      year (88.7 vs 93.9%), 5-year (82.6 vs 89.4%) and 10-year (65.5 vs 75.3%) follow
      up. Other complications including 30-day mortality, strokes, respiratory failure,
      pneumonia and hospitalization were significantly higher in the POAF group. New
      onset AF following coronary bypass surgery is associated with significantly
      higher risk of mortality in short- and long-term follow-up. Current evidence
      suggests the need for stricter surveillance and monitoring of POAF following
      coronary bypass surgery.

PMID- 25602054
TI  - Suprasternal direct aortic approach transcatheter aortic valve replacement avoids
      sternotomy and thoracotomy: first-in-man experience?.
AB  - OBJECTIVES: Direct aortic deployment of a transcatheter aortic valve eliminates
      the need to traverse the aortic arch with the valve delivery system, enables
      placement of large sheaths in the aorta and innominate artery, provides maximal
      precision during deployment and ensures a safe, conventional surgical aortotomy
      closure. We describe the initial experience with the Suprasternal Aortic Access
      System (SuprAA System, Aegis Surgical Ltd, Dublin, Ireland) for direct
      transaortic/innominate valve delivery. METHODS: Patients with severe, symptomatic
      aortic stenosis who were candidates for transcatheter aortic valve replacement
      (TAVR) via a direct transaortic approach were enrolled in the SuprAA-TAVR First
      in-Man Study. Under general anaesthesia, the innominate artery and aortic arch
      were exposed in each patient, using the SuprAA System via a 2.5-cm incision
      directly above the sternal notch. The TAVR delivery sheath was positioned and the
      transcatheter valve deployed routinely under fluoroscopic guidance. Upon sheath
      removal, haemostasis at the aortotomy site was confidently secured using a double
      purse-string suture closure. All were extubated immediately. A meta-analysis of
      the direct aortic approach was done for comparison. RESULTS: Four male patients
      (mean 82.5 years) underwent SuprAA-TAVR (2 CoreValve; 2 SAPIEN). Anatomical
      visualization was excellent and suprasternal valve deployment was accurate
      regardless of sheath size with 100% Valve Academic Research Consortium-2
      procedural success. The average total procedure time was 109.5 min without
      perioperative wound or vascular complications. CONCLUSIONS: The SuprAA System
      provides direct aortic/innominate access without sternal or thoracotomy incision.
      Patient recovery to normal activity is maximized, sheath size limitations are
      eliminated and valve deployment is precise. This innovative system creates a new
      and exciting minimally invasive approach for high-risk patients with aortic
      stenosis.

PMID- 25602055
TI  - Results of heart transplantation following failed staged palliation of
      hypoplastic left heart syndrome and related single ventricle anomalies.
AB  - OBJECTIVES: Multistage palliation is the mainstay management strategy of children
      with hypoplastic left heart syndrome (HLHS) and related single ventricle
      anomalies. If this palliation strategy fails, heart transplantation (HT) is
      required. The results of HT in children who had a prior Norwood operation are
      reportedly poor due to several immune, clinical and anatomical risk factors. We
      report our institutional outcomes following HT in children who had a prior
      Norwood operation. METHODS: Between 1994 and 2013, 107 children with congenital
      heart disease underwent HT. We examined early and late outcomes in our study
      cohort of children who had a prior Norwood operation (n = 24), and analysed risk
      factors affecting survival. Survival was subsequently compared with a control
      group of 83 children with congenital heart disease without a prior Norwood
      operation who received HT. RESULTS: Twenty-four children with a prior Norwood
      operation underwent HT. The majority (22/24, 92%) had HLHS. Children were listed
      following Norwood (n = 2, 8.3%), Glenn (n = 17, 70.8%) or Fontan (n = 5, 20.8%)
      operation. Ten (42%) patients had panel reactive antibodies (PRAs) >10%. Median
      age at listing was 2.7 (range 0.4-16.8) years and median age at the time of HT
      was 3.0 (range 0.6-16.8) years, with the median waiting list duration of 63.5
      (range 1-554) days. Hospital mortality was 1/24 (4%). Overall parametric survival
      estimates at 1, 5 and 10 years were 85, 65 and 52%. Survival was not affected by
      listing status, last palliation stage, age or high PRA. The only significant
      factor affecting survival was the later era in our series with significantly
      superior 5-year survival (100 vs 42%, P = 0.0003). Overall survival was
      comparable with the control group of children with congenital heart disease and
      no prior Norwood operation (52 vs 53% at 10 years, P = 0.97). Overall, 3 of 24
      patients required retransplantation with only one late survivor. CONCLUSIONS:
      Children failing multistage palliation of HLHS may require HT, often following
      the Glenn operation. HT results in this group are comparable with those in other
      children with congenital heart disease. Improvements in pretransplant management,
      immune suppression and outpatient care in the later era might have specifically
      benefited this particularly risky group of patients.

PMID- 25602057
TI  - V-composite grafting using the right internal thoracic artery grafts anastomosed
      to aorto-coronary bypass grafts.
AB  - OBJECTIVES: Composite grafting using the right internal thoracic artery (RITA) is
      occasionally performed when the in situ RITA does not have sufficient length to
      reach the target vessel. In this study, we assessed the clinical and angiographic
      outcomes of coronary artery bypass grafting (CABG) with V-composite grafting
      (defined as a distance between the proximal anastomosis of the RITA and the
      ascending aorta of <=1 cm) using the RITA anastomosed to aortocoronary (A-C)
      bypass grafts. METHODS: Between September 2004 and December 2012, 177 patients
      underwent CABG with V-composite grafting using the RITA and the A-C bypass graft
      [radial artery (RA) or saphenous vein graft (SVG)] at our institution. The mean
      age was 69.2 +/- 8.5 years and 149 (84.2%) were men. The clinical outcomes and
      patency rates of distal anastomoses of the composite RITA were retrospectively
      evaluated. RESULTS: Mean distal anastomoses per patient were 4.6 +/- 1.0, and
      mean distal anastomoses of the RITA per patient were 1.3 +/- 0.5. Inflow conduit
      of the RITA was the RA in 16 (9.0%) patients and an SVG in 161 (91.0%) patients.
      The 30-day mortality rate was 1.1% (2/177). The overall patency rate of distal
      anastomoses of the composite RITA on early (before discharge) and follow-up (at 1
      year) angiography was 97.6 and 93.6%, respectively. The inflow conduit (RA or
      SVG), stenosis grade of target vessel and sequential grafting did not affect the
      patency rate of the composite RITA. CONCLUSIONS: V-composite grafting using the
      RITA and the A-C bypass graft provides excellent clinical outcomes with
      satisfactory early and 1-year patency rates.

PMID- 25602056
TI  - Lung transplantation for emphysema: impact of age on short- and long-term
      survival.
AB  - OBJECTIVES: Overall, emphysema (EMP) is the most common indication for lung
      transplantation. The majority of patients present with chronic obstructive
      pulmonary disease (COPD) and less frequently with alpha-1 antitrypsin deficiency
      (A1ATD). We analysed the results of lung transplants performed for EMP in order
      to identify the impact of age on short- and long-term outcome. METHODS: A
      retrospective analysis was undertaken of the 108 consecutive lung transplants for
      EMP performed at our institution from November 1992 to August 2013 (77 COPD, 31
      A1ATD). Retransplantations were excluded. RESULTS: The median age was 56 years
      (range 31-68). Thirty-day mortality rate was 3.7%. One- and 5-year survival rates
      in COPD and A1ATD recipients were comparable (P = 0.8). The 1- and 5-year
      survival rates for recipients aged <60 years old were significantly better than
      the age group of >=60 years (91 and 79 vs 84 and 54%, P = 0.05). Since 2007, the
      1- and 5-year survival for these two age groups were 96 and 92 vs 86 and 44%,
      respectively, P = 0.04, log-rank test). For the following parameters, we were not
      able to find any difference to affect survival rates: use of intraoperative
      extracorporeal membrane oxygenation, waiting list time, sex, graft size
      reduction, body mass index and diagnosis. In multivariate analysis, age at
      transplantation (>=60 years old) (HR 2.854; 95% confidence interval (CI) 1.338
      6.08, P = 0.008) and unilateral lung transplantation (HR 15.2; 95% CI 3.2-71.9, P
      = 0.009) were independent risk factors for mortality. CONCLUSIONS: COPD and A1ATD
      recipients have similar overall long-term survival. Recipients aged >=60 years
      and unilateral lung transplants were risk factors for mortality.

PMID- 25602058
TI  - Acute type A aortic dissection repair in elderly patients.
AB  - OBJECTIVES: We evaluated our experience in acute type A aortic dissection (ATAAD)
      repair in elderly patients. The role of clinical presentation and surgical
      strategies in determining patients' outcome was further assessed. METHODS: A
      retrospective analysis of patients over 75 years who underwent emergency repair
      of ATAAD at our institution during 2000-13 was performed. Forty-five patients
      (mean age = 79 +/- 3 years; 26 females) were identified. Aortic dissection was
      complicated in 17 (37%) patients with new neurological deficit (n = 5), cardiac
      tamponade (n = 12), acute myocardial infarction (n = 5) and acute renal failure
      (n = 2). The ascending aorta was replaced in all patients and hypothermic
      circulatory arrest was employed in 22 patients. The aortic replacement needed
      extension to the hemiarch in 11 patients and the aortic valve was replaced in 9
      patients; in 3 cases, full root replacement was performed. RESULTS: The in
      hospital mortality rate was 15% (n = 7). Preoperative acute neurological deficit
      was the only independent risk factor for mortality (P = 0.03). Age >80 years old
      per se was not associated with a poor outcome. Surgical strategies and extension
      of aortic wall resection did not affect the operative mortality. The
      postoperative course was complicated in 23 (52%) patients. During the median
      follow-up of 57 months, there were 4 late deaths. The cumulative 1-, 5- and 8
      year survival rates were 82, 76 and 67%, respectively. CONCLUSIONS: Emergency
      surgical repair of ATAAD in elderly patients resulted in an acceptable early
      mortality rate and satisfactory intermediate survival. Preoperative acute
      neurological deficit predicts a worse outcome. Advanced age alone should not be
      considered as a contraindication to AAD repair.

PMID- 25602059
TI  - Comprehensive rhythm evaluation in a large contemporary Fontan population.
AB  - OBJECTIVES: Rhythm disturbances are an important cause of morbidity in Fontan
      patients. Currently, the total cavopulmonary connection is performed by using the
      intra-atrial lateral tunnel (ILT) ('baffle ILT' or 'prosthetic ILT'), or the
      extracardiac conduit (ECC). The aim of the study was to evaluate rhythm
      abnormalities and compare the surgical techniques in a contemporary cohort.
      METHODS: In a cross-sectional multicentre study, 115 patients (age 12.5 +/- 3.1
      years) underwent rhythm evaluation using ECG, exercise testing and Holter,
      including heart rate variability. Medical history was reviewed for episodes of
      arrhythmia. RESULTS: Sinus node dysfunction (SND) was found in 29%, 3 of whom
      required pacemaker therapy. No difference was found in the incidence of SND
      between ILT and ECC patients. Sinus pauses occurred only in the ILT group.
      Exercise testing showed no difference in peak heart rate between the groups.
      Heart rate reserve (P = 0.023) and heart rate recovery (HRrecovery) (P < 0.001)
      were lower in ILT patients. Atrial arrhythmias were more common in ILT patients
      (15 vs 1%, P = 0.004), but only in those with a baffle ILT. One patient had
      symptomatic ventricular tachycardia (VT). Holter recordings showed sub-clinical
      VT in 6% of patients, which was associated with larger end-diastolic (P = 0.035)
      and end-systolic volumes (P = 0.029). CONCLUSIONS: The overall incidence of
      arrhythmia was low, although SND was frequently present in both Fontan groups.
      ILT patients had slower HRrecovery, and ILT patients with the more extensive
      baffle technique had more atrial arrhythmias and more sinus pauses. The
      significance of asymptomatic ventricular arrhythmias in this young population
      remains to be determined.

PMID- 25602060
TI  - Impact of the entry site on late outcome in acute Stanford type B aortic
      dissection?.
AB  - OBJECTIVES: This study aimed to investigate whether the entry site of acute type
      B aortic dissection affects late outcomes. METHODS: Inpatient and outpatient
      records were retrospectively reviewed. RESULTS: We identified 224 cases of acute
      type B aortic dissection between 1998 and 2013. Of these 224 patients, 168 were
      men and the age was 64.2 +/- 12.6 (range 23-94) years, from which 130 presented
      with the entry at a location downstream of the distal aortic arch, 67 with the
      entry at the outer curvature of the distal aortic arch and 27 with the entry at
      the inner curvature. At the initial presentation, 127 patients had descending
      false lumen thrombosis. The 30-day mortality rate was 2%, and 8% of patients had
      malperfusion. The entry at the outer curvature was associated with a higher risk
      of 30-day mortality. Patients with the entry at a location downstream were
      significantly older, and had a higher chance for primarily thrombosed descending
      false lumen and a lower risk of malperfusion. At follow-up (6.0 +/- 4.1 years),
      the actuarial survival rates were 97, 83 and 60%, freedoms from open aortic
      surgery were 96, 91 and 86%, aortic intervention were 73, 66 and 63% and aortic
      events were 71, 60 and 52% at 1, 5 and 10 years, respectively. Multivariate
      logistic regression analysis revealed that the outer curvature entry and maximum
      aortic diameter were correlated with open aortic surgery, aortic intervention and
      aortic events. Of the 127 patients with primarily thrombosed false lumen, the
      outer curvature entry was significantly correlated with aortic events.
      CONCLUSIONS: The primary entry at the outer curvature of the distal aortic arch,
      as well as the large aortic diameter, is associated with a higher risk of late
      open aortic surgery, aortic intervention and aortic events in acute type B aortic
      dissection. Thus, the entry site should be taken into consideration in the
      establishment of an appropriate treatment indication of type B aortic dissection.

PMID- 25602061
TI  - Abnormalities of selenium but not of copper homeostasis may drive tissue fibrosis
      in patients with systemic sclerosis.

PMID- 25602062
TI  - Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like
      phenotype in PSTPIP2-deficient mice.
AB  - OBJECTIVE: Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2)
      is involved in macrophage activation, neutrophil motility and osteoclast
      differentiation. However, the role of PSTPIP2 in inflammation and
      autoinflammatory diseases is still not clear. In this study, we generated PSTPIP2
      knockout (Pstpip2(-/-)) mice to investigate its phenotype and role in
      autoinflammatory diseases. METHODS: We constructed a Pstpip2-targeting vector and
      generated Pstpip2(-/-) mice. The phenotype and immunopathology of Pstpip2(-/-)
      mice were analysed. RESULTS: All Pstpip2(-/-) mice developed paw swelling,
      synovitis, hyperostosis and osteitis, resembling SAPHO syndrome, an inflammatory
      disorder of the bone, skin and joints. Multifocal osteomyelitis was found in
      inflamed paws, with increased macrophage and marked neutrophil infiltrations in
      the bone, joint and skin. Profound osteolytic lesions with markedly decreased
      bone volume density developed in paws and limbs. Neutrophil-attracting chemokines
      and IL-1beta were markedly elevated in inflamed tissues. CONCLUSION: Our study
      suggests that PSTPIP2 could play a role in innate immunity and development of
      autoinflammatory bone disorders, and may be associated with the pathogenesis of
      human SAPHO syndrome.

PMID- 25602063
TI  - Comment on: tocilizumab induces corticosteroid sparing in rheumatoid arthritis
      patients in clinical practice: reply.

PMID- 25602064
TI  - Comment on: tocilizumab induces corticosteroid sparing in rheumatoid arthritis
      patients in clinical practice.

PMID- 25602065
TI  - Human evolution: brain, birthweight and the immune system.

PMID- 25602066
TI  - Brain ontogeny and life history in Pleistocene hominins.
AB  - A high level of encephalization is critical to the human adaptive niche and
      emerged among hominins over the course of the past 2 Myr. Evolving larger brains
      required important adaptive adjustments, in particular regarding energy
      allocation and life history. These adaptations included a relatively small brain
      at birth and a protracted growth of highly dependent offspring within a complex
      social environment. In turn, the extended period of growth and delayed maturation
      of the brain structures of humans contribute to their cognitive complexity. The
      current palaeoanthropological evidence shows that, regarding life history and
      brain ontogeny, the Pleistocene hominin taxa display different patterns and that
      one cannot simply contrast an 'ape-model' to a 'human-model'. Large-brained
      hominins such as Upper Pleistocene Neandertals have evolved along their own
      evolutionary pathway and can be distinguished from modern humans in terms of
      growth pattern and brain development. The life-history pattern and brain ontogeny
      of extant humans emerged only recently in the course of human evolution.

PMID- 25602067
TI  - The evolution of the human pelvis: changing adaptations to bipedalism, obstetrics
      and thermoregulation.
AB  - The fossil record of the human pelvis reveals the selective priorities acting on
      hominin anatomy at different points in our evolutionary history, during which
      mechanical requirements for locomotion, childbirth and thermoregulation often
      conflicted. In our earliest upright ancestors, fundamental alterations of the
      pelvis compared with non-human primates facilitated bipedal walking. Further
      changes early in hominin evolution produced a platypelloid birth canal in a
      pelvis that was wide overall, with flaring ilia. This pelvic form was maintained
      over 3-4 Myr with only moderate changes in response to greater habitat diversity,
      changes in locomotor behaviour and increases in brain size. It was not until Homo
      sapiens evolved in Africa and the Middle East 200 000 years ago that the narrow
      anatomically modern pelvis with a more circular birth canal emerged. This major
      change appears to reflect selective pressures for further increases in neonatal
      brain size and for a narrow body shape associated with heat dissipation in warm
      environments. The advent of the modern birth canal, the shape and alignment of
      which require fetal rotation during birth, allowed the earliest members of our
      species to deal obstetrically with increases in encephalization while maintaining
      a narrow body to meet thermoregulatory demands and enhance locomotor performance.

PMID- 25602068
TI  - A synthesis of the theories and concepts of early human evolution.
AB  - Current evidence suggests that many of the major events in hominin evolution
      occurred in East Africa. Hence, over the past two decades, there has been
      intensive work undertaken to understand African palaeoclimate and tectonics in
      order to put together a coherent picture of how the environment of Africa has
      varied over the past 10 Myr. A new consensus is emerging that suggests the
      unusual geology and climate of East Africa created a complex, environmentally
      very variable setting. This new understanding of East African climate has led to
      the pulsed climate variability hypothesis that suggests the long-term drying
      trend in East Africa was punctuated by episodes of short alternating periods of
      extreme humidity and aridity which may have driven hominin speciation,
      encephalization and dispersals out of Africa. This hypothesis is unique as it
      provides a conceptual framework within which other evolutionary theories can be
      examined: first, at macro-scale comparing phylogenetic gradualism and punctuated
      equilibrium; second, at a more focused level of human evolution comparing
      allopatric speciation, aridity hypothesis, turnover pulse hypothesis, variability
      selection hypothesis, Red Queen hypothesis and sympatric speciation based on
      sexual selection. It is proposed that each one of these mechanisms may have been
      acting on hominins during these short periods of climate variability, which then
      produce a range of different traits that led to the emergence of new species. In
      the case of Homo erectus (sensu lato), it is not just brain size that changes but
      life history (shortened inter-birth intervals, delayed development), body size
      and dimorphism, shoulder morphology to allow thrown projectiles, adaptation to
      long-distance running, ecological flexibility and social behaviour. The future of
      evolutionary research should be to create evidence-based meta-narratives, which
      encompass multiple mechanisms that select for different traits leading ultimately
      to speciation. 

PMID- 25602069
TI  - Primate pelvic anatomy and implications for birth.
AB  - The pelvis performs two major functions for terrestrial mammals. It provides
      somewhat rigid support for muscles engaged in locomotion and, for females, it
      serves as the birth canal. The result for many species, and especially for
      encephalized primates, is an 'obstetric dilemma' whereby the neonate often has to
      negotiate a tight squeeze in order to be born. On top of what was probably a
      baseline of challenging birth, locomotor changes in the evolution of bipedalism
      in the human lineage resulted in an even more complex birth process. Negotiation
      of the bipedal pelvis requires a series of rotations, the end of which has the
      infant emerging from the birth canal facing the opposite direction from the
      mother. This pattern, strikingly different from what is typically seen in monkeys
      and apes, places a premium on having assistance at delivery. Recently reported
      observations of births in monkeys and apes are used to compare the process in
      human and non-human primates, highlighting similarities and differences. These
      include presentation (face, occiput anterior or posterior), internal and external
      rotation, use of the hands by mothers and infants, reliance on assistance, and
      the developmental state of the neonate. 

PMID- 25602070
TI  - The placenta: a multifaceted, transient organ.
AB  - The placenta is arguably the most important organ of the body, but paradoxically
      the most poorly understood. During its transient existence, it performs actions
      that are later taken on by diverse separate organs, including the lungs, liver,
      gut, kidneys and endocrine glands. Its principal function is to supply the fetus,
      and in particular, the fetal brain, with oxygen and nutrients. The placenta is
      structurally adapted to achieve this, possessing a large surface area for
      exchange and a thin interhaemal membrane separating the maternal and fetal
      circulations. In addition, it adopts other strategies that are key to
      facilitating transfer, including remodelling of the maternal uterine arteries
      that supply the placenta to ensure optimal perfusion. Furthermore, placental
      hormones have profound effects on maternal metabolism, initially building up her
      energy reserves and then releasing these to support fetal growth in later
      pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic
      challenges to the placental circulation, as pressure applied to the vena cava by
      the pregnant uterus may compromise venous return to the heart. These challenges,
      along with the immune interactions involved in maternal arterial remodelling, may
      explain complications of pregnancy that are almost unique to the human, including
      pre-eclampsia. Such complications may represent a trade-off against the provision
      for a large fetal brain. 

PMID- 25602071
TI  - Between Scylla and Charybdis: renegotiating resolution of the 'obstetric dilemma'
      in response to ecological change.
AB  - Hominin evolution saw the emergence of two traits-bipedality and encephalization
      that are fundamentally linked because the fetal head must pass through the
      maternal pelvis at birth, a scenario termed the 'obstetric dilemma'. While
      adaptive explanations for bipedality and large brains address adult phenotype, it
      is brain and pelvic growth that are subject to the obstetric dilemma. Many
      contemporary populations experience substantial maternal and perinatal
      morbidity/mortality from obstructed labour, yet there is increasing recognition
      that the obstetric dilemma is not fixed and is affected by ecological change.
      Ecological trends may affect growth of the pelvis and offspring brain to
      different extents, while the two traits also differ by a generation in the timing
      of their exposure. Two key questions arise: how can the fit between the maternal
      pelvis and the offspring brain be 'renegotiated' as the environment changes, and
      what nutritional signals regulate this process? I argue that the potential for
      maternal size to change across generations precludes birthweight being under
      strong genetic influence. Instead, fetal growth tracks maternal phenotype, which
      buffers short-term ecological perturbations. Nevertheless, rapid changes in
      nutritional supply between generations can generate antagonistic influences on
      maternal and offspring traits, increasing the risk of obstructed labour. 

PMID- 25602072
TI  - Uterine artery blood flow, fetal hypoxia and fetal growth.
AB  - Evolutionary trade-offs required for bipedalism and brain expansion influence the
      pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive
      success. We consider the importance of UtA blood flow by reviewing its
      determinants and presenting data from 191 normotensive (normal, n = 125) or
      hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean
      residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior
      studies show that UtA blood flow is reduced in pregnancies with intrauterine
      growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia
      is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia
      in normotensive women at high versus low altitude but similar fetal growth. UtA
      blood flow was markedly lower in early-onset PE versus normal high-altitude
      women, and their fetuses more hypoxic as indicated by lower fetal heart rate,
      Doppler indices and greater IUGR. We concluded that, despite greater fetal
      hypoxia, fetal growth was well defended by higher UtA blood flows in normal
      Andeans at high altitude but when compounded by lower UtA blood flow in early
      onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing
      cardiac output and redistributing blood flow to help maintain brain development
      at the expense of growth elsewhere. We speculate that UtA blood flow is not only
      an important supply line but also a trigger for stimulating the metabolic and
      other processes regulating feto-placental metabolism and growth. Studies using
      the natural laboratory of high altitude are valuable for identifying the
      physiological and genetic mechanisms involved in human reproductive success. 

PMID- 25602073
TI  - Genetic recapitulation of human pre-eclampsia risk during convergent evolution of
      reduced placental invasiveness in eutherian mammals.
AB  - The relationship between phenotypic variation arising through individual
      development and phenotypic variation arising through diversification of species
      has long been a central question in evolutionary biology. Among humans, reduced
      placental invasion into endometrial tissues is associated with diseases of
      pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also
      evolved, convergently, in at least 10 lineages of eutherian mammals. We tested
      the hypothesis that a common genetic basis underlies both reduced placental
      invasion arising through a developmental process in human placental disease and
      reduced placental invasion found as a derived trait in the diversification of
      Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based
      on whole-genome analyses across 18 taxa, we identified 1254 genes as having
      evolved adaptively across all three lineages exhibiting independent evolutionary
      transitions towards reduced placental invasion. These genes showed strong
      evidence of enrichment for associations with pre-eclampsia, based on genetic
      association studies, gene-expression analyses and gene ontology. We further used
      in silico prediction to identify a subset of 199 genes that are likely targets of
      natural selection during transitions in placental invasiveness and which are
      predicted to also underlie human placental disorders. Our results indicate that
      abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian
      evolution, identify new candidate genes for involvement in pre-eclampsia, imply
      that study of species with less-invasive placentation will provide useful
      insights into the regulation of placental invasion and pre-eclampsia, and
      recommend a novel comparative functional-evolutionary approach to the study of
      genetically based human disease and mammalian diversification. 

PMID- 25602074
TI  - The role of invasive trophoblast in implantation and placentation of primates.
AB  - We here review the evolution of invasive placentation in primates towards the
      deep penetration of the endometrium and its arteries in hominoids. The
      strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial
      placentation, although this is thought to be derived from a more invasive type.
      In haplorhine primates, there is differentiation of trophoblast at the blastocyst
      stage into syncytial and cellular trophoblast. Implantation involves
      syncytiotrophoblast that first removes the uterine epithelium then consolidates
      at the basal lamina before continuing into the stroma. In later stages of
      pregnancy, especially in Old World monkeys and apes, cytotrophoblast plays a
      greater role in the invasive process. Columns of trophoblast cells advance to the
      base of the implantation site where they spread out to form a cytotrophoblastic
      shell. In addition, cytotrophoblasts advance into the lumen of the spiral
      arteries. They are responsible for remodelling these vessels to form wide, low
      resistance conduits. In human and great apes, there is additional invasion of the
      endometrium and its vessels by trophoblasts originating from the base of the
      anchoring villi. Deep trophoblast invasion that extends remodelling of the spiral
      arteries to segments in the inner myometrium evolved in the common ancestor of
      gorilla, chimp and human. 

PMID- 25602075
TI  - The role of the maternal immune system in the regulation of human birthweight.
AB  - Human birthweight is subject to stabilizing selection. Large babies are at risk
      of obstetric complications such as obstructed labour, which endangers both mother
      and child. Small babies are also at risk with reduced survival. Fetal growth
      requires remodelling of maternal spiral arteries to provide an adequate maternal
      blood supply to the placenta. This arterial transformation is achieved by
      placental trophoblast cells, which invade into the uterine wall. Under-invasion
      is associated with fetal growth restriction; but if invasion is excessive large
      babies can result. A growing body of evidence suggests that this process is
      controlled by interactions between killer-cell immunoglobulin-like receptors
      (KIRs) expressed on maternal uterine natural killer cells (uNK) and their
      corresponding human leukocyte antigen-C (HLA-C) ligands on invading trophoblast.
      Mothers with the KIR AA genotype and a fetus with a paternal HLA-C2 allele tend
      to have small babies, because this combination inhibits cytokine secretion by
      uNK. Mothers with the activating KIR2DS1 gene and an HLA-C2 fetus are more likely
      to have large babies. When KIR2DS1 binds to HLA-C2 this increases secretion of
      cytokines that enhance trophoblast invasion. We conclude that specific
      combinations of the highly polymorphic gene systems, KIR and HLA-C, contribute to
      successful reproduction by maintaining birthweight between two extremes. 

PMID- 25602076
TI  - A review of inter- and intraspecific variation in the eutherian placenta.
AB  - The placenta is one of the most morphologically variable mammalian organs. Four
      major characteristics are typically discussed when comparing the placentas of
      different eutherian species: placental shape, maternal-fetal interdigitation,
      intimacy of the maternal-fetal interface and the pattern of maternal-fetal blood
      flow. Here, we describe the evolution of three of these features as well as other
      key aspects of eutherian placentation. In addition to interspecific anatomical
      variation, there is also variation in placental anatomy and function within a
      single species. Much of this intraspecific variation occurs in response to
      different environmental conditions such as altitude and poor maternal nutrition.
      Examinations of variation in the placenta from both intra- and interspecies
      perspectives elucidate different aspects of placental function and dysfunction at
      the maternal-fetal interface. Comparisons within species identify candidate
      mechanisms that are activated in response to environmental stressors ultimately
      contributing to the aetiology of obstetric syndromes such as pre-eclampsia.
      Comparisons above the species level identify the evolutionary lineages on which
      the potential for the development of obstetric syndromes emerged. 

PMID- 25602078
TI  - Correction to 'Neural systems for landmark-based wayfinding in humans'.

PMID- 25602079
TI  - Public effective doses from environmental natural gamma exposures indoors and
      outdoors in Iran.
AB  - The effective doses of public in Iran due to external gamma exposures from
      terrestrial radionuclides and from cosmic radiation indoors and outdoors of
      normal natural background radiation areas were determined by measurements and by
      calculations. For direct measurements, three measurement methods were used
      including a NaI(TI) scintillation survey meter for preliminary screening, a
      pressurised ionising chamber for more precise measurements and early warning
      measurement equipment systems. Measurements were carried out in a large number of
      locations indoors and outdoors ~1000 houses selected randomly in 36 large cities
      of Iran. The external gamma doses of public from living indoors and outdoors were
      also calculated based on the radioactivity measurements of samples taken from
      soil and building materials by gamma spectrometry using a high-resolution HPGe
      system. The national mean background gamma dose rates in air indoors and outdoors
      based on measurements are 126.9+/-24.3 and 111.7+/-17.72 nGy h(-1), respectively.
      When the contribution from cosmic rays was excluded, the values indoors and
      outdoors are 109.2+/-20.2 and 70.2+/-20.59.4 nGy h(-1), respectively. The dose
      rates determined for indoors and outdoors by calculations are 101.5+/-9.2 and
      72.2+/-9.4 nGy h(-1), respectively, which are in good agreement with directly
      measured dose rates within statistical variations. By considering a population
      weighted mean for terrestrial radiation, the ratio of indoor to outdoor dose
      rates is 1.55. The mean annual effective dose of each individual member of the
      public from terrestrial radionuclides and cosmic radiation, indoors and outdoors,
      is 0.86+/-0.16 mSv y(-1) by measurements and 0.8+/-0.2 mSv y(-1) by calculations.
      The results of this national survey of public annual effective doses from
      national natural background external gamma radiation determined by measurements
      and calculations indoors and outdoors of 1000 houses in 36 cities of Iran are
      presented and discussed.

PMID- 25602077
TI  - The role and interaction of imprinted genes in human fetal growth.
AB  - Identifying the genetic input for fetal growth will help to understand common,
      serious complications of pregnancy such as fetal growth restriction. Genomic
      imprinting is an epigenetic process that silences one parental allele, resulting
      in monoallelic expression. Imprinted genes are important in mammalian fetal
      growth and development. Evidence has emerged showing that genes that are
      paternally expressed promote fetal growth, whereas maternally expressed genes
      suppress growth. We have assessed whether the expression levels of key imprinted
      genes correlate with fetal growth parameters during pregnancy, either early in
      gestation, using chorionic villus samples (CVS), or in term placenta. We have
      found that the expression of paternally expressing insulin-like growth factor 2
      (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly
      correlate with crown-rump length and birthweight, whereas term placenta
      expression shows no correlation. For the maternally expressing pleckstrin
      homology-like domain family A, member 2 (PHLDA2), there is no correlation early
      in pregnancy in CVS but a highly significant negative relationship in term
      placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to
      a maternally and compounded grand-maternally controlled genetic effect with a
      birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2
      promoter variant is inherited. Expression of the growth factor receptor-bound
      protein 10 (GRB10) in term placenta is significantly negatively correlated with
      head circumference. Analysis of the paternally expressing delta-like 1 homologue
      (DLK1) shows that the paternal transmission of type 1 diabetes protective G
      allele of rs941576 single nucleotide polymorphism (SNP) results in significantly
      reduced birth weight (-132 g). In conclusion, we have found that the expression
      of key imprinted genes show a strong correlation with fetal growth and that for
      both genetic and genomics data analyses, it is important not to overlook parent
      of-origin effects. 

PMID- 25602083
TI  - The status of the species Hyphomonas rosenbergii Weiner et al. 2000. Request for
      an Opinion.
AB  - On the basis of 16S rRNA gene sequence analysis and several key phenotypic
      features, it was ascertained that the culture cited as the type strain of the
      species Hyphomonas rosenbergii, ATCC 43869(T), does not conform to the
      description of the species, [Weiner, R. M., Melick, M., O'Neill, K. & Quintero,
      E. (2000). Int J Syst Evol Microbiol 50, 459-469]. The type strain does not exist
      in any other established culture collection or with the authors who described
      this species. Therefore, it cannot be included in any scientific study. It is
      proposed that the Judicial Commission place the name Hyphomonas rosenbergii on
      the list of rejected names if a suitable replacement type strain is not found or
      a neotype is not proposed within two years following the publication of this
      Request for an Opinion. 

PMID- 25602085
TI  - Wilbrand's knee and the dilemma of textbooks.

PMID- 25602084
TI  - The relationship of weekend admission and mortality on the public medical wards
      at a Kenyan referral hospital.
AB  - BACKGROUND: Research has demonstrated disparities in the outcomes of patients
      admitted to hospital on weekends in high-income countries. No published research
      has evaluated if any similar discrepancy exists in low-resource settings.
      METHODS: To determine if any difference in mortality exists between weekend and
      weekday admissions on the public medical wards at a Kenyan referral hospital, we
      performed a retrospective observational study of inpatients over a 3-month study
      period. RESULTS: During the study period, 261 (27.3%) of the 956 patients were
      admitted over the weekend. The mortality rates for patients admitted on weekends
      and weekdays did not differ with 156 (22.4%) of the 695 patients admitted on
      weekdays dying compared to 55 (21.1%) of the 261 patients admitted on weekends.
      After adjusting for age, insurance status, co-morbid illness, HIV status,
      employment, referral status and gender, still no association existed between
      weekend admission and mortality. CONCLUSIONS: Among adult patients on the medical
      wards, patients admitted on weekends had similar mortality rates to those
      admitted on weekdays. This similarity may reflect a stable level of care or a
      generalized shortage of resources and staffing that subsumes any impact of weekly
      variations. Future research examining optimal staffing and resource levels is
      needed in such settings.

PMID- 25602087
TI  - An unusual mechanism of asystole.

PMID- 25602086
TI  - [Albert Jovell (1962-2013), doctor and patient].

PMID- 25602088
TI  - Work-life balance: Lab life with kids.

PMID- 25602089
TI  - Dynamic size responses to climate change: prevailing effects of rising
      temperature drive long-term body size increases in a semi-arid passerine.
AB  - Changes in animal body size have been widely reported as a correlate of
      contemporary climate change. Body size affects metabolism and fitness, so
      changing size has implications for resilience, yet the climatic factors that
      drive size variation remain poorly understood. We test the role of mean and
      extreme temperature, rainfall, and remotely sensed primary productivity (NDVI) as
      drivers of body size in a sedentary, semi-arid Australian passerine, Ptilotula
      (Lichenostomus)penicillatus, over 23 years. To distinguish effects due to
      differential growth from changes in population composition, we analysed first
      year birds and adults separately and considered climatic variation at three
      temporal scales (current, previous, and preceding 5 years). The strongest effects
      related to temperature: in both age classes, larger size was associated with
      warmer mean temperatures in the previous year, contrary to Bergmann's Rule.
      Moreover, adults were larger in warmer breeding seasons, while first years was
      larger after heat waves; these effects are more likely to be mediated through
      size-dependent mortality, highlighting the role of body size in determining
      vulnerability to extinction. In addition to temperature, larger adult size was
      associated with lower primary productivity, which may reflect a trade-off between
      vegetative growth and nectar production, on which adults rely. Finally, lower
      rainfall was associated with decreasing size in first year and adults, most
      likely related to decreased food availability. Overall,body size increased over
      23 years, strongly in first-year birds (2.7%) compared with adults (1%), with
      size outcomes a balance between competing drivers. As rainfall declined over time
      and productivity remained fairly stable, the temporal increase in body size
      appears largely driven by rising mean temperature and temperature extremes. Body
      size responses to environmental change are thus complex and dynamic, driven by
      effects on growth as well as mortality.

PMID- 25602090
TI  - Highlights in B-cell malignancies from the 2012 American Society of Hematology
      (ASH) Meeting.

PMID- 25602091
TI  - Ronald James (Jim) Methven.

PMID- 25602092
TI  - James Blaul Kriechbaum.

PMID- 25602093
TI  - Literature review: use of respite by carers of people with dementia.
AB  - Respite care is a cornerstone service for the home management of people with
      dementia. It is used by carers to mitigate the stress related to the demands of
      caring by allowing time for them to rest and do things for themselves, thus
      maintaining the caring relationship at home and perhaps forestalling long-term
      placement in a residential aged care facility. Despite numerous anecdotal reports
      in support of respite care, its uptake by carers of people with dementia remains
      relatively low. The aim of this paper was to examine the factors that constitute
      the use of respite by carers of people with dementia by reviewing quantitative
      and qualitative research predominantly from the years 1990 to 2012. Seventy-six
      international studies of different types of respite care were included for this
      review and their methods were critically appraised. The key topics identified
      were in relation to information access, the barriers to carers realising need for
      and seeking respite, satisfaction with respite services including the outcomes
      for carers and people with dementia, the characteristics of an effective respite
      service and the role of health workers in providing appropriate respite care.
      Finally, limitations with considering the literature as a whole were highlighted
      and recommendations made for future research.

PMID- 25602094
TI  - [Reply].

PMID- 25602095
TI  - European euthanasia laws: questions of compassion.

PMID- 25602096
TI  - 56th ASTRO annual meeting.

PMID- 25602099
TI  - ESMO 2014 Congress.

PMID- 25602098
TI  - Earlier cancer diagnosis would reduce NHS costs.

PMID- 25602097
TI  - Lung cancer screening less accurate with endemic lung disease.

PMID- 25602100
TI  - Maintenance pazopanib in ovarian cancer.

PMID- 25602101
TI  - Assessment and approval of drugs to be reviewed in the UK.

PMID- 25602102
TI  - Testing urine for cervical human papillomavirus.

PMID- 25602103
TI  - UK Early Access to Medicines Scheme.

PMID- 25602104
TI  - France announces tobacco legislation plan.

PMID- 25602105
TI  - US legislation has little eff ect on chemotherapy prescribing.

PMID- 25602106
TI  - New therapeutic target for non-small-cell lung cancer.

PMID- 25602107
TI  - Quality of life with treated acute promyelocytic leukaemia.

PMID- 25602108
TI  - Inadequate funding for rare cancers in Australia.

PMID- 25602109
TI  - Antibody-drug conjugate for advanced melanoma?

PMID- 25602110
TI  - Vemurafenib and cobimetinib in BRAF-mutated melanoma.

PMID- 25602111
TI  - Thoracoscopic lobectomy versus thoracotomy for NSCLC.

PMID- 25602112
TI  - T-cell therapy for paediatric acute lymphoblastic leukaemia.

PMID- 25602113
TI  - Intratumour heterogeneity in lung cancer.

PMID- 25602114
TI  - Prediction model for heart failure in childhood cancer survivors.

PMID- 25602116
TI  - [On the special issue on "therapeutic strategy for left-sided cardiac
      hypoplasia"].

PMID- 25602115
TI  - Guanylin hormone loss could trigger colon cancer.

PMID- 25602117
TI  - Ultrasensitive in vivo detection of primary gastric tumor and lymphatic
      metastasis using upconversion nanoparticles.
AB  - Lymphatic metastasis is an important prognostic factor regarding long-term
      survival rate of gastric cancer (GC) patients. Pretreatment knowledge of lymph
      node status is extremely helpful for planning treatment and prognosis. However,
      to date, no imaging method has been demonstrated to be effective for detecting
      lymphatic metastasis in GC. Molecular imaging probes based on upconversion
      nanoparticles with unique optical and magnetic properties have provided great
      hope for early tumor detection. Herein we report highly sensitive detection of
      lymphatic spread using core@shell structured NaGdF4:Yb,Er@NaGdF4 upconversion
      nanoparticles coated with polyethylene glycol (PEG). A GC-specific probe was
      constructed through "click" reaction between the maleimide moiety of PEG ligand
      and the thiol group from partly reduced antigastric cancer antibody MGb2. The
      primary tumor and adjacent lymphatic metastasis site were clearly differentiated
      by upconversion luminescence imaging after the GC-specific probe was delivered
      through tail vein injection into tumor-bearing mice. Moreover, lymphatic
      metastases smaller than 1 mm were successfully detected, owing to the ultralow
      background under 980 nm excitation. It has been demonstrated that both primary
      and lymphatic metastatic sites in an orthotopic mouse model of human gastric
      cancer can be optically detected by using GC-specific upconversion luminescence
      nanoprobes. The current studies may therefore provide a highly effective approach
      for GC diagnosis. 

PMID- 25602118
TI  - Electrolytically exfoliated graphene-loaded flame-made Ni-doped SnO2 composite
      film for acetone sensing.
AB  - In this work, flame-spray-made SnO2 nanoparticles are systematically studied by
      doping with 0.1-2 wt % nickel (Ni) and loading with 0.1-5 wt % electrolytically
      exfoliated graphene for acetone-sensing applications. The sensing films (~12-18
      MUm in thickness) were prepared by a spin-coating technique on Au/Al2O3
      substrates and evaluated for acetone-sensing performances at operating
      temperatures ranging from 150 to 350  degrees C in dry air. Characterizations by
      X-ray diffraction, transmission/scanning electron microscopy, Brunauer-Emmett
      Teller analysis, X-ray photoelectron spectroscopy and Raman spectroscopy
      demonstrated that Ni-doped SnO2 nanostructures had a spheriodal morphology with a
      polycrystalline tetragonal SnO2 phase, and Ni was confirmed to form a solid
      solution with SnO2 lattice while graphene in the sensing film after annealing and
      testing still retained its high-quality nonoxidized form. Gas-sensing results
      showed that SnO2 sensing film with 0.1 wt % Ni-doping concentration exhibited an
      optimal response of 54.2 and a short response time of ~13 s toward 200 ppm
      acetone at an optimal operating temperature of 350  degrees C. The additional
      loading of graphene at 5 wt % into 0.1 wt % Ni-doped SnO2 led to a drastic
      response enhancement to 169.7 with a very short response time of ~5.4 s at 200
      ppm acetone and 350  degrees C. The superior gas sensing performances of Ni-doped
      SnO2 nanoparticles loaded with graphene may be attributed to the large specific
      surface area of the composite structure, specifically the high interaction rate
      between acetone vapor and graphene-Ni-doped SnO2 nanoparticles interfaces and
      high electronic conductivity of graphene. Therefore, the 5 wt % graphene loaded
      0.1 wt % Ni-doped SnO2 sensor is a promising candidate for fast, sensitive and
      selective detection of acetone.

PMID- 25602119
TI  - Job insecurity and organizational citizenship behavior: exploring curvilinear and
      moderated relationships.
AB  - This article examined a curvilinear relationship between job insecurity and
      organizational citizenship behavior (OCB). Drawing from social exchange theory
      and research on personal control, we developed and tested an explanation for
      employees' reactions to job insecurity based on their conceptualization of their
      social exchange relationship with the organization at different levels of job
      insecurity. Using data from 244 Chinese employees and 102 supervisory ratings of
      OCB, we found support for a U-shaped relationship between job insecurity and OCB.
      Moreover, 2 factors--psychological capital and subordinate-supervisor guanxi-
      moderated the curvilinear relationship, such that the curvilinear relationship is
      more pronounced among those with lower psychological capital or less positive
      subordinate-supervisor guanxi.

PMID- 25602120
TI  - Work demands, family demands, and BMI in dual-earners families: A 16-year
      longitudinal study.
AB  - Many scholars assert that work and family demands are negatively related to
      individuals' long-term physical health, but few studies have explicitly examined
      this relationship. Among these exceptions, most have employed a cross-sectional
      design that is limited in its ability to establish causality. We use body mass
      index (BMI) that generally increases during one's lifetime as an indicator of
      physical health, and seek to explore the amount of control individuals may have
      on this seemingly inevitable progression. Drawing on conservation of resources
      theory, we propose that an increase in demands-both in the work realm (e.g., the
      number of work hours) and in the family realm (e.g., the number of spouse work
      hours)-is likely to speed up the increase of BMI. Using a nationally
      representative sample of 4,264 individuals who were part of a dual-earner family
      between 1994 and 2010, we find that a within-person increase in weekly work
      hours, an increase in spouse weekly work hours, and an increase in the number of
      children are all related to a small within-person increase of the BMI growth
      trajectory. Within-person increase in work responsibility demands is related to a
      small within-person decrease in the BMI growth trajectory. We discuss
      implications of the relationships between work and family demands and long-term
      physical health.

PMID- 25602121
TI  - Sinking slowly: Diversity in propensity to trust predicts downward trust spirals
      in small groups.
AB  - This paper examines the phenomenon of trust spirals in small groups. Drawing on
      literature on the spiral reinforcement of trust, we theorize that diversity in
      propensity to trust has affective and cognitive consequences related to trust
      (i.e., feelings of frustration and perceptions of low similarity), reducing the
      level of experienced intragroup trust early in a group's development. Reduced
      experienced trust then fuels relationship conflict and lowers trust even further
      over time, ultimately having a negative effect on group performance. These ideas
      are tested using a sample of MBA student groups surveyed at 3 time periods over 4
      months. Results confirm our hypothesis that diversity in propensity to trust is
      sufficient to trigger a downward trust spiral and poor performance in small
      groups.

PMID- 25602122
TI  - It is worse when you do it: Examining the interactive effects of coworker
      presenteeism and demographic similarity.
AB  - Presenteeism (showing up for work while sick) is detrimental for employee
      productivity, yet little is known about its impact on coworkers. Presenteeism may
      be particularly important when considering coworker reactions that may depend on
      how similar the sick person is to the coworker. The black sheep hypothesis
      suggests that the detrimental effects of coworker presenteeism on emotional and
      behavioral reactions will be exacerbated when there is greater demographic
      similarity to the perpetrator because the violation of norms of reciprocity,
      empathy, and concern for others' well-being reflects negatively on one's in
      group. We tested the black sheep hypothesis in 2 samples: (a) 81 short-term teams
      (N = 254) where we manipulated presenteeism using confederates who acted as
      either sick or healthy coworkers and (b) 34 student project teams (N = 104) that
      collaborated for 3 months and we measured coworker presenteeism. Across the
      studies, mediated moderation results yielded some support for the black sheep
      hypothesis. When they were of the same race or sex, coworker presenteeism led
      participants to feel less positively and exhibit lower physical engagement and
      more organizational deviance (Study 1). When coworkers were more racially similar
      to the participant, coworker presenteeism triggered fear of contagion and
      negative affect resulting in more organizational and interpersonal deviance
      (Study 2).

PMID- 25602123
TI  - It's all in the attitude: The role of job attitude strength in job attitude
      outcome relationships.
AB  - Integrating attitude theory with the job attitudes literature, we position job
      attitude strength (JAS) as a missing yet important theoretical concept in the
      study of job attitudes. We examine JAS as a moderator of the relationship between
      job satisfaction and several criteria of interest to organizational scholars (job
      performance, organizational citizenship behavior, withdrawal). We also examine
      multiple relevant indicators of JAS (i.e., attitude certainty, attitude
      extremity, latitude of rejection, and structural consistency), both to shed light
      on its conceptual nature and to provide meaningful practical direction to
      researchers interested in incorporating JAS into job attitude research. Data were
      collected in five field samples (total N = 816). Results support our hypotheses:
      JAS moderates the relationships between job satisfaction and performance,
      organizational citizenship behavior, and turnover intentions; in each case, these
      relationships are significantly stronger for employees with stronger job
      satisfaction attitudes. However, as expected, not all JAS indicators are equally
      effective as moderators. We discuss our findings in terms of their theoretical,
      empirical, and practical implications for the future study of job attitudes.

PMID- 25602124
TI  - Cross-lagged relations between mentoring received from supervisors and employee
      OCBs: Disentangling causal direction and identifying boundary conditions.
AB  - Although mentoring has documented relationships with employee attitudes and
      outcomes of interest to organizations, neither the causal direction nor boundary
      conditions of the relationship between mentoring and organizational citizenship
      behaviors (OCBs) has been fully explored. On the basis of Social Learning Theory
      (SLT; Bandura, 1977, 1986), we predicted that mentoring received by supervisors
      would causally precede OCBs, rather than employee OCBs resulting in the receipt
      of more mentoring from supervisors. Results from cross-lagged data collected at 2
      points in time from 190 intact supervisor-employee dyads supported our
      predictions; however, only for OCBs directed at individuals (OCB-Is) and not for
      OCBs directed at the organization (OCB-Os). Further supporting our theoretical
      rationale for expecting mentoring to precede OCBs, we found that coworker support
      operates as a substitute for mentoring in predicting OCB-Is. By contrast, no
      moderating effects were found for perceived organizational support. The results
      are discussed in terms of theoretical implications for mentoring and OCB
      research, as well as practical suggestions for enhancing employee citizenship
      behaviors.

PMID- 25602125
TI  - Toward a meaningful metric of implicit prejudice.
AB  - [Correction Notice: An Erratum for this article was reported in Vol 100(5) of
      Journal of Applied Psychology (see record 2015-40760-001). there are errors in
      some of the values listed in Table 6 that do not alter any of the conclusions or
      substantive statements in the original article. The corrected portion of Table 6
      is in the correction. The positive intercepts in this table represent the
      estimated IAT score when the criterion has a value of zero (suggesting
      attitudinal neutrality), except in the equation examining voter preference in
      Greenwald et al. (2009), where the intercept estimated the IAT score of Obama
      voters.] The modal distribution of the Implicit Association Test (IAT) is
      commonly interpreted as showing high levels of implicit prejudice among
      Americans. These interpretations have fueled calls for changes in organizational
      and legal practices, but such applications are problematic because the IAT is
      scored on an arbitrary psychological metric. The present research was designed to
      make the IAT metric less arbitrary by determining the scores on IAT measures that
      are associated with observable racial or ethnic bias. By reexamining data from
      published studies, we found evidence that the IAT metric is "right biased," such
      that individuals who are behaviorally neutral tend to have positive IAT scores.
      Current scoring conventions fail to take into account these dynamics and can lead
      to faulty inferences about the prevalence of implicit prejudice.

PMID- 25602127
TI  - Adrenal reserve following treatment of Graves' orbitopathy with intravenous
      glucocorticoids.

PMID- 25602128
TI  - The effect of metronidazole on the presence of P. gingivalis and T. forsythia at
      3 and 12 months after different periodontal treatment strategies evaluated in a
      randomized, clinical trial.
AB  - OBJECTIVE: The benefit of full-mouth disinfection (FDIS) over traditional scaling
      and root planing (SRP) in the treatment of chronic, destructive periodontitis
      remains equivocal and it is not known whether the use of adjunctive antibiotics
      may enhance the effect of FDIS. Therefore, the aim of this study was to evaluate
      the effect of conventional SRP completed over 21 days or 1-day FDIS, with or
      without systemically delivered adjunctive metronidazole (MET) on the presence of
      P. gingivalis and T. forsythia after 3 and 12 months. MATERIALS AND METHODS: One
      hundred and eighty-four patients with moderate-to-severe periodontitis were
      randomly allocated to one of four treatment groups; (1) FDIS+MET; (2)
      FDIS+placebo; (3) SRP+MET; (4) SRP+placebo. Prior to treatment, pooled
      subgingival samples were obtained from the five deepest pockets. The same sites
      were sampled again 3 and 12 months after treatment. All samples were analyzed for
      P. gingivalis and T. forsythia by PCR, whereas A. actinomycetemcomitans and other
      bacteria were identified by culture techniques. RESULTS: At baseline, 47% of the
      samples were positive for P. gingivalis, while almost all samples were positive
      for T. forsythia. The occurrence of P. gingivalis and T. forsythia was
      significantly reduced at 3 and 12 months after treatment in the FDIS+MET group,
      but not in the other treatment groups. CONCLUSION: FDIS+MET had a significant
      effect in patients with P. gingivalis and T. forsythia, resulting in a
      significant reduction in number of patients where these micro-organisms could be
      detected at 3 and 12 months post-therapy.

PMID- 25602126
TI  - Synthesis and pharmacological characterization of C4-disubstituted analogs of
      1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate: identification of a
      potent, selective metabotropic glutamate receptor agonist and determination of
      agonist-bound human mGlu2 and mGlu3 amino terminal domain structures.
AB  - As part of our ongoing research to identify novel agents acting at metabotropic
      glutamate 2 (mGlu2) and 3 (mGlu3) receptors, we have previously reported the
      identification of the C4alpha-methyl analog of mGlu2/3 receptor agonist 1
      (LY354740). This molecule, 1S,2S,4R,5R,6S-2-amino-4-methylbicyclo[3.1.0]hexane
      2,6-dicarboxylate 2 (LY541850), exhibited an unexpected mGlu2 agonist/mGlu3
      antagonist pharmacological profile, whereas the C4beta-methyl diastereomer (3)
      possessed dual mGlu2/3 receptor agonist activity. We have now further explored
      this structure-activity relationship through the preparation of cyclic and
      acyclic C4-disubstituted analogs of 1, leading to the identification of C4
      spirocyclopropane 5 (LY2934747), a novel, potent, and systemically bioavailable
      mGlu2/3 receptor agonist which exhibits both antipsychotic and analgesic
      properties in vivo. In addition, through the combined use of protein-ligand X-ray
      crystallography employing recombinant human mGlu2/3 receptor amino terminal
      domains, molecular modeling, and site-directed mutagenesis, a molecular basis for
      the observed pharmacological profile of compound 2 is proposed. 

PMID- 25602129
TI  - DRIFTS evidence for facet-dependent adsorption of gaseous toluene on TiO2 with
      relative photocatalytic properties.
AB  - Effective adsorption is of great importance to the photocatalytic degradation of
      volatile organic compounds. Herein, we succeeded in the preparation of anatase
      TiO2 with clean dominant {001} and {101} facets. By using in situ diffuse
      reflectance infrared Fourier transform spectroscopy (DRIFTS) equipped with a
      homemade reaction system and a coupling gas-dosing system, we found that TiO2
      with dominant {001} facets exhibits higher toluene adsorption capacity than TiO2
      with dominant {101} facets, which may be attributed to the different number of
      unsaturated 5c-Ti capable of forming the main active adsorption sites (terminal
      Ti-OH species). TiO2 with dominant {001} facets shows a significantly high
      photocatalytic degradation performance, with its degradation rate being 6 times
      higher than that of dominant {101} facets. Combined with simulation results, it
      is suggested that the synergetic effects of the formation of specific active
      adsorption sites, the low adsorption energy for toluene, and preservation of the
      free molecularly adsorbed water on the surface promote the degradation of gaseous
      toluene on the dominant {001} facets. This study exemplifies that the facet
      dependent adsorption of volatile organic compounds is one of the most important
      factors to effectively engineer photocatalysts for air purification. 

PMID- 25602130
TI  - Nanoparticles in photodynamic therapy.

PMID- 25602131
TI  - Steps to strengthen ethics in organizations: research findings, ethics placebos,
      and what works.
AB  - Research shows that many organizations overlook needs and opportunities to
      strengthen ethics. Barriers can make it hard to see the need for stronger ethics
      and even harder to take effective action. These barriers include the
      organization's misleading use of language, misuse of an ethics code, culture of
      silence, strategies of justification, institutional betrayal, and ethical
      fallacies. Ethics placebos tend to take the place of steps to see, solve, and
      prevent problems. This article reviews relevant research and specific steps that
      create change. 

PMID- 25602133
TI  - Conservative management for postprostatectomy urinary incontinence.
AB  - BACKGROUND: Urinary incontinence is common after radical prostatectomy and can
      also occur in some circumstances after transurethral resection of the prostate
      (TURP). Conservative management includes pelvic floor muscle training with or
      without biofeedback, electrical stimulation, extra-corporeal magnetic innervation
      (ExMI), compression devices (penile clamps), lifestyle changes, or a combination
      of methods. OBJECTIVES: To determine the effectiveness of conservative management
      for urinary incontinence up to 12 months after transurethral, suprapubic,
      laparoscopic, radical retropubic or perineal prostatectomy, including any single
      conservative therapy or any combination of conservative therapies. SEARCH
      METHODS: We searched the Cochrane Incontinence Group Specialised Register (5
      February 2014), CENTRAL (2014, Issue 1), EMBASE (January 2010 to Week 3 2014),
      CINAHL (January 1982 to 18 January 2014), ClinicalTrials.gov and World Health
      Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (both
      searched 29 January 2014), and the reference lists of relevant articles.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating
      conservative interventions for urinary continence in men after prostatectomy.
      DATA COLLECTION AND ANALYSIS: Two or more review authors assessed the
      methodological quality of the trials and abstracted data. We tried to contact
      several authors of included studies to obtain extra information. MAIN RESULTS:
      Fifty trials met the inclusion criteria, 45 in men after radical prostatectomy,
      four trials after TURP and one trial after either operation. The trials included
      4717 men of whom 2736 had an active conservative intervention. There was
      considerable variation in the interventions, populations and outcome measures.
      Data were not available for many of the pre-stated outcomes. Men's symptoms
      improved over time irrespective of management.There was no evidence from eight
      trials that pelvic floor muscle training with or without biofeedback was better
      than control for men who had urinary incontinence up to 12 months after radical
      prostatectomy; the quality of the evidence was judged to be moderate (for example
      57% with urinary incontinence in the intervention group versus 62% in the control
      group, risk ratio (RR) for incontinence after 12 months 0.85, 95% confidence
      interval (CI) 0.60 to 1.22). One large multi-centre trial of one-to-one therapy
      showed no difference in any urinary or quality of life outcome measures and had
      narrow CIs. It seems unlikely that men benefit from one-to-one PFMT therapy after
      TURP. Individual small trials provided data to suggest that electrical
      stimulation, external magnetic innervation, or combinations of treatments might
      be beneficial but the evidence was limited. Amongst trials of conservative
      treatment for all men after radical prostatectomy, aimed at both treatment and
      prevention, there was moderate evidence of an overall benefit from pelvic floor
      muscle training versus control management in terms of reduction of urinary
      incontinence (for example 10% with urinary incontinence after one year in the
      intervention groups versus 32% in the control groups, RR for urinary incontinence
      0.32, 95% CI 0.20 to 0.51). However, this finding was not supported by other data
      from pad tests. The findings should be treated with caution because the risk of
      bias assessment showed methodological limitations. Men in one trial were more
      satisfied with one type of external compression device, which had the lowest
      urine loss, compared to two others or no treatment. The effect of other
      conservative interventions such as lifestyle changes remained undetermined as no
      trials involving these interventions were identified. AUTHORS' CONCLUSIONS: The
      value of the various approaches to conservative management of postprostatectomy
      incontinence after radical prostatectomy remains uncertain. The evidence is
      conflicting and therefore rigorous, adequately powered randomised controlled
      trials (RCTs) which abide by the principles and recommendations of the CONSORT
      statement are still needed to obtain a definitive answer. The trials should be
      robustly designed to answer specific well constructed research questions and
      include outcomes which are important from the patient's perspective in decision
      making and are also relevant to the healthcare professionals. Long-term
      incontinence may be managed by an external penile clamp, but there are safety
      problems.

PMID- 25602132
TI  - Distinct features of lamin A-interacting chromatin domains mapped by ChIP
      sequencing from sonicated or micrococcal nuclease-digested chromatin.
AB  - The nuclear lamina has been shown to interact with the genome through lamina
      associated domains (LADs). LADs have been identified by DamID, a proximity
      labeling assay, and more recently by chromatin immunoprecipitation-sequencing
      (ChIP-seq) of A- and B-type lamins. LADs form megabase-size domains at the
      nuclear periphery, they are gene-poor and mostly heterochromatic. Here, we show
      that the mode of chromatin fragmentation for ChIP, namely bath sonication or
      digestion with micrococcal nuclease (MNase), leads to the discovery of common but
      also distinct sets of lamin-interacting domains, or LiDs. Using ChIP-seq, we show
      the existence of lamin A/C (LMNA) LiDs with distinct gene contents, histone
      composition enrichment and relationships to lamin B1-interacting domains. The
      extent of genome coverage of lamin A/C (LMNA) LiDs in sonicated or MNase-digested
      chromatin is similar (~730 megabases); however over half of these domains are
      uniquely detected in sonicated or MNase-digested chromatin. Sonication-specific
      LMNA LiDs are gene-poor and devoid of a broad panel of histone modifications,
      while MNase-specific LMNA LiDs are of higher gene density and are enriched in
      H3K9me3, H3K27me3 and in histone variant H2A.Z. LMNB1 LiDs are gene-poor and show
      no or little enrichment in these marks. Comparison of published LMNB1 DamID LADs
      with LMNB1 and LMNA LiDs identified here by ChIP-seq further shows that LMNA can
      associate with 'open' chromatin domains displaying euchromatin characteristics,
      and which are not associated with LMNB1. The differential genomic and epigenetic
      properties of lamin-interacting domains reflect the existence of distinct LiD
      populations identifiable in different chromatin contexts, including nuclease
      accessible regions presumably localized in the nuclear interior. 

PMID- 25602135
TI  - Comparison of invasive and non-invasive pressure gradients in aortic arch
      obstruction.
AB  - BACKGROUND: Aortic arch obstruction can be evaluated by catheter peak-to-peak
      gradient or by Doppler peak instantaneous pressure gradient. Previous studies
      have shown moderate correlation in discrete coarctation, but few have assessed
      correlation in patients with more complex aortic reconstruction. METHODS: We
      carried out retrospective comparison of cardiac catheterisations and pre- and
      post-catheterisation echocardiograms in 60 patients with native/recurrent
      coarctation or aortic reconstruction. Aortic arch obstruction was defined as peak
      to-peak gradient ?25 mmHg in patients with native/recurrent coarctation and ?10
      mmHg in aortic reconstruction. RESULTS: Diastolic continuation of flow was not
      associated with aortic arch obstruction in either group. Doppler peak
      instantaneous pressure gradient, with and without the expanded Bernoulli
      equation, weakly correlated with peak-to-peak gradient even in patients with a
      normal cardiac index (r=0.36, p=0.016, and r=0.49, p=0.001, respectively).
      Receiver operating characteristic curve analysis identified an area under the
      curve of 0.61 for patients with all types of obstruction, with a cut-off point of
      45 mmHg correctly classifying 64% of patients with arch obstruction (sensitivity
      39%, specificity 89%). In patients with aortic arch reconstruction who had a
      cardiac index ?3 L/min/m2, a cut-off point of 23 mmHg correctly classified 69% of
      patients (71% sensitivity, 50% specificity) with an area under the curve of 0.82.
      CONCLUSION: The non-invasive assessment of aortic obstruction remains
      challenging. The greatest correlation of Doppler indices was noted in patients
      with aortic reconstruction and a normal cardiac index.

PMID- 25602136
TI  - A reproducible method for the expansion of mouse CD8+ T lymphocytes.
AB  - Murine adoptive CD8+ T-cell immunotherapy studies require the generation of large
      numbers of high viability CD8+ cells. Here we report a tissue culture protocol
      for the reliable expansion of CD8+ T-cells derived from murine spleen to give a
      20-fold expansion after 4 days in culture. The cells were transfected with an
      mRNA GFP construct and transferred into NOD mice. GFP positive cells could be
      detected 7 days after transfer thus confirming that the cells survive and are
      functional for up to 1 week.

PMID- 25602134
TI  - Serotonin deficiency alters susceptibility to the long-term consequences of
      adverse early life experience.
AB  - Brain 5-HT deficiency has long been implicated in psychiatric disease, but the
      effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early
      life stress (ELS) has been suggested to contribute to adult psychopathology, but
      efforts to study the long-term consequences of ELS have been limited by a lack of
      appropriate preclinical models. Here, we evaluated the effects of 5-HT deficiency
      on several long-term cellular, molecular, and behavioral responses of mice to a
      new model of ELS that combines early-life maternal separation (MS) of pups and
      postpartum learned helplessness (LH) training in dams. Our data demonstrate that
      this paradigm (LH/MS) induces depressive-like behavior and impairs pup retrieval
      in dams. In addition, we show that brain 5-HT deficiency exacerbates anxiety-like
      behavior induced by LH/MS and blunts the effects of LH/MS on acoustic startle
      responses in adult offspring. Although the mechanisms underlying these effects
      remain unclear, following LH/MS, 5-HT-deficient animals had significantly less
      mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type
      animals. In addition, 5-HT-deficient mice exhibited reduced mRNA levels of the 5
      HT2a receptor and p11 in the hippocampus regardless of stress. LH/MS decreased
      the number of doublecortin+ immature neurons in the hippocampus in both wild-type
      (WT) and 5-HT-deficient animals. Our data emphasize the importance of complex
      interactions between genetic factors and early life experience in mediating long
      term changes in emotional behavior. These findings may have important
      implications for our understanding of the combinatorial roles of 5-HT deficiency,
      ELS, and postpartum depression in the development of neuropsychiatric disorders. 

PMID- 25602138
TI  - The physical self in motion: within-person change and associations of change in
      self-esteem, physical self-concept, and physical activity in adolescent girls.
AB  - The purpose of this study was to examine patterns of within-person change, and
      associations of change, in global self-esteem (GSE), physical self-perceptions
      (PSP), and physical activity in a sample of 705 Canadian adolescent girls over
      three measurements points and 24 months. The Physical Self-Perceptions Profile
      (PSPP) was used to measure GSE and PSP, and the Physical Activity Questionnaire
      for Adolescents (PAQ-A) was used to assess physical activity. Latent growth curve
      models were used to analyze the data. All PSP variables except for body
      attractiveness demonstrated significant average decline, but also significant was
      the change in between-person heterogeneity. Change in GSE and PSP was moderately
      to strongly related on a between-person level and weakly to moderately associated
      on a within-person level. Change in physical activity was related to change in
      the majority of the PSP variables but not to change in GSE. 

PMID- 25602137
TI  - A fit-for-purpose strategy for the risk-based immunogenicity testing of
      biotherapeutics: a European industry perspective.
AB  - There is much debate in the pharmaceutical industry on how to translate the
      current guidelines on immunogenicity testing for biotherapeutics into a testing
      strategy that suits the specific requirements of individual drug candidates. In
      this paper, member companies from the European immunogenicity platform (EIP)
      present a consensus view on the essential requirements for immunogenicity testing
      of a biotherapeutic throughout the various phases of drug development, to ensure
      patient safety and to enable successful market entry. Our aim is to open the
      debate and provoke discussion on this important topic which is unique to
      biotherapeutic drug development. The scope of this paper is limited to aspects
      relevant to biotherapeutic drug development and does not include fundamental
      academic studies of immunogenicity. Here, we propose two pre-defined testing
      strategies for the detection and characterization of anti-drug antibody (ADA)
      responses where the different strategies are based on the phase of development
      for a biotherapeutic, a. without (category 1) and b. with (category 2) the
      expected potential to elicit ADA mediated severe clinical consequences. The harm
      of a potential ADA response determines which of the two testing strategies is
      adopted. Rather than replacing the overall risk assessment which is known to be
      challenging and multi-factorial, the testing strategy selection is a starting
      point for immunogenicity testing which adapts throughout drug development as more
      information becomes available. The scientific rationale on which the "case-by
      case" approach advocated in white papers and guidance documents may be translated
      for each individual drug development program is provided and, underpins the
      recommendations made here. 

PMID- 25602139
TI  - Breast cancer survivors' decisions to join a dragon boating team.
AB  - Physical activity is associated with psychosocial and physical health benefits
      for breast cancer survivors. Little is known, however, about survivors' decision
      making processes when considering joining group physical activity programs
      designed for survivors. Guided by interpretive description methodology (Thorne,
      2008), N = 15 breast cancer survivors who were considering or had made the
      decision to join a dragon boating team were interviewed about their decisions to
      participate. Four patterns of decision making were identified: searching for a
      way to care for physical and social needs, taking advantage of opportunities
      created by breast cancer, dove in with little contemplation, and hesitant to
      connect with other survivors. Results have implications for understanding
      decisions to participate in physical activity groups in this population and
      overcoming challenges to participation. 

PMID- 25602140
TI  - The influence of the physical education environment on children's well-being and
      physical activity across the transition from primary to secondary school.
AB  - The purpose of the study was to explore change in children's physical self
      concept and self-reported physical activity over a school transition period, as
      well as motivational and interpersonal influences on these two outcomes. Data
      were collected from 545 children (mean age = 10.82, SD = 0.39, 51% female) at
      three time points before and after the United Kingdom secondary school
      transition. Multilevel modeling revealed that physical self-concept and physical
      activity showed different patterns of decline over the course of the study.
      Changes in the extent to which physical education teachers were perceived to
      provide psychological need support, peer focus on self-referenced learning and
      mastery, and changes in autonomous motives toward physical education classes were
      positively associated with these outcome variables. The present study provides
      novel insight into important motivational and interpersonal factors that may need
      to be targeted to prevent negative developmental patterns over a potentially
      challenging period for children. 

PMID- 25602141
TI  - Participation in organized sport and self-esteem across adolescence: the
      mediating role of perceived sport competence.
AB  - The purpose of the study was to test longitudinal (2 years across three
      occasions) associations between sport participation (SP) and self-esteem (SE)
      across adolescence (10-18 years), addressing the mediating role of perceived
      sport competence (PSC) from a developmental perspective. Three waves of data were
      collected from three age cohorts (10-12, 13-15, and 16-18 years) of school-aged
      youth (N = 1358). The results demonstrate that SP and SE are related across time
      and that PSC has an important mediating role in this relationship, both from a
      skill development and a self-enhancement perspective. In the skill development
      model, the mediating role of PSC was significantly stronger in the youngest
      cohort whereas the effect of PSC on subsequent SP in the self-enhancement model
      was significantly stronger in the 13-15 age group compared with the youngest age
      group. 

PMID- 25602142
TI  - Fostering a need-supportive teaching style: intervention effects on physical
      education teachers' beliefs and teaching behaviors.
AB  - The present intervention study examined whether physical education (PE) teachers
      can learn to make use of autonomy-supportive and structuring teaching strategies.
      In a sample of 39 teachers (31 men, M = 38.51 +/- 10.44 years) and 669 students
      (424 boys, M = 14.58 +/- 1.92 years), we investigated whether a professional
      development training grounded in self-determination theory led to changes in (a)
      teachers' beliefs about the effectiveness and feasibility of autonomy-supportive
      and structuring strategies and (b) teachers' in-class reliance on these
      strategies, as rated by teachers, external observers, and students. The
      intervention led to positive changes in teachers' beliefs regarding both autonomy
      support and structure. As for teachers' actual teaching behavior, the
      intervention was successful in increasing autonomy support according to students
      and external observers, while resulting in positive changes in teacher-reported
      structure. Implications for professional development and recommendations for
      future research are discussed. 

PMID- 25602143
TI  - Effect of six weeks of sprint interval training on mood and perceived health in
      women at risk for metabolic syndrome.
AB  - The purpose of this investigation was to determine whether 6 weeks of sprint
      interval training (SIT) is associated with changes in mood and perceived health
      in women at risk for developing metabolic syndrome (MetS). Physically inactive
      women (30-65 years) were randomized to 6 weeks of nutrition meetings and SIT (n =
      23; 3 bouts/week of 4-8 30-s cycle sprints with 4-min recovery) or a nonexercise
      control condition (CON; n = 24). Before and after the 6-week intervention,
      perceived health status and mood were assessed. Clinically relevant increases in
      role-physical scores (ES = 0.64) and vitality (ES = 0.52) were found after 6
      weeks of SIT compared with a nonexercise control group. For middle-aged women at
      risk for MetS, it is concluded that high-intensity, low-volume SIT (1) increases
      feelings of vitality and perceptions of having fewer physical limitations and (2)
      does not induce mood disturbances as occurs with high-volume, high-intensity
      training. 

PMID- 25602144
TI  - Athlete social support, negative social interactions and psychological health
      across a competitive sport season.
AB  - Social support and negative social interactions have implications for athlete
      psychological health, with potential to influence the links of stress-related
      experiences with burnout and well-being over time. Using a longitudinal design,
      perceived social support and negative social interactions were examined as
      potential moderators of the temporal stress-burnout and burnout-well-being
      relationships. American collegiate athletes (N = 465) completed reliable and
      valid online assessments of study variables at four time points during the
      competitive season. After controlling for dispositional and conceptually
      important variables, social support and negative social interactions did not
      moderate the stress-burnout or burnout-well-being relationships, respectively,
      but did simultaneously contribute to burnout and well-being across the
      competitive season. The results showcase the importance of sport-related social
      perceptions to athlete psychological outcomes over time and inform development of
      socially driven interventions to improve the psychological health of competitive
      athletes. 

PMID- 25602145
TI  - Automatic evaluations and exercise setting preference in frequent exercisers.
AB  - The goals of this study were to test whether exercise-related stimuli can elicit
      automatic evaluative responses and whether automatic evaluations reflect exercise
      setting preference in highly active exercisers. An adapted version of the Affect
      Misattribution Procedure was employed. Seventy-two highly active exercisers (26
      years +/- 9.03; 43% female) were subliminally primed (7 ms) with pictures
      depicting typical fitness center scenarios or gray rectangles (control primes).
      After each prime, participants consciously evaluated the "pleasantness" of a
      Chinese symbol. Controlled evaluations were measured with a questionnaire and
      were more positive in participants who regularly visited fitness centers than in
      those who reported avoiding this exercise setting. Only center exercisers gave
      automatic positive evaluations of the fitness center setting (partial eta squared
      = .08). It is proposed that a subliminal Affect Misattribution Procedure paradigm
      can elicit automatic evaluations to exercising and that, in highly active
      exercisers, these evaluations play a role in decisions about the exercise setting
      rather than the amounts of physical exercise. Findings are interpreted in terms
      of a dual systems theory of social information processing and behavior. 

PMID- 25602148
TI  - Simultaneous determination of acidic pesticides in vegetables and fruits by
      liquid chromatography--tandem mass spectrometry.
AB  - A sensitive and efficient method has been developed for the simultaneous
      determination of 73 multi-class acidic pesticides, such as phenoxy acid and
      sulfonylurea herbicides, in vegetables and fruits. The sample preparation
      procedure was carefully optimized for the efficient removal of co-extracted
      matrix components. The method involves extraction of acidic pesticides with
      acetonitrile containing hydrochloric acid, removal of water from crude extract by
      salting out, and sequential cleanup by octadecylsilyl silica gel and silica gel
      columns. For samples containing high amounts of pigments, such as spinach,
      additional cleanup using a graphitized carbon column was performed prior to
      liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Recovery tests were
      performed for five times for each sample of cabbage, spinach, potato, eggplant,
      orange, and apple fortified at 0.01 mg kg-1. Out of the 73 tested pesticides, 70
      for cabbage, 67 for spinach, 69 for potato, 67 for eggplant, 64 for orange, and
      70 for apple were within the range of 70-120%, with relative standard deviations
      below 25%. Nitenpyram and pyrasulfotole showed low recoveries for all the samples
      tested, probably due to low recoveries from silica gel column. The developed
      method effectively removed co-extracted matrix components and was highly
      selective, with no interfering peaks found in the chromatograms of blank samples.
      The overall results indicate that the developed method is suitable for the
      quantitative analysis of acidic pesticide residues in vegetables and fruits.

PMID- 25602149
TI  - Residues and potential health risks of DDTs and HCHs in commercial seafoods from
      two coastal cities near Yangtze River Estuary.
AB  - Five species of commercial seafoods collected from the local markets in two
      coastal cities near Yangtze River Estuary (Ningbo and Zhoushan) in 2010 were
      analyzed to study the residues, potential sources, and health risks of
      dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) in
      these areas. The total levels of DDTs and HCHs in the samples ranged from 1.13
      20.2 ng g(-1) and 1.23-3.05 ng g(-1) wet weight, respectively, and were at a
      middle level compared with those from other marine systems. Results from one-way
      analysis of variance (ANOVA) indicated species-specific distributions of DDTs and
      HCHs in the seafoods of the studied area, which may be related to their different
      lipid contents and ecological characteristics. Compositional analysis suggested
      that historical usage dominates in this area, and fresh inputs of lindane and
      dicofol may also have part contributions. With respect to DDTs, it can be
      metabolized into both DDD and DDE simultaneously in seafoods tested. Assessment
      based on maximum residue levels, acceptable or tolerable daily intakes, and
      hazard ratios for non-carcinogens suggested no obvious adverse health effects,
      while the lifetime cancer risks may be increased from dietary exposure to DDTs
      and HCHs.

PMID- 25602147
TI  - A delay prior to mitotic entry triggers caspase 8-dependent cell death in p53
      deficient Hela and HCT-116 cells.
AB  - Stathmin/Oncoprotein 18, a microtubule destabilizing protein, is required for
      survival of p53-deficient cells. Stathmin-depleted cells are slower to enter
      mitosis, but whether delayed mitotic entry triggers cell death or whether
      stathmin has a separate pro-survival function was unknown. To test these
      possibilities, we abrogated the cell cycle delay by inhibiting Wee1 in
      synchronized, stathmin-depleted cells and found that apoptosis was reduced to
      control levels. Synchronized cells treated with a 4 hour pulse of inhibitors to
      CDK1 or both Aurora A and PLK1 delayed mitotic entry and apoptosis was triggered
      only in p53-deficient cells. We did not detect mitotic defects downstream of the
      delayed mitotic entry, indicating that cell death is activated by a mechanism
      distinct from those activated by prolonged mitotic arrest. Cell death is
      triggered by initiator caspase 8, based on its cleavage to the active form and by
      rescue of viability after caspase 8 depletion or treatment with a caspase 8
      inhibitor. In contrast, initiator caspase 9, activated by prolonged mitotic
      arrest, is not activated and is not required for apoptosis under our experimental
      conditions. P53 upregulates expression of cFLIPL, a protein that blocks caspase 8
      activation. cFLIPL levels are lower in cells lacking p53 and these levels are
      reduced to a greater extent after stathmin depletion. Expression of FLAG-tagged
      cFLIPL in p53-deficient cells rescues them from apoptosis triggered by stathmin
      depletion or CDK1 inhibition during G2. These data indicate that a cell cycle
      delay in G2 activates caspase 8 to initiate apoptosis specifically in p53
      deficient cells. 

PMID- 25602150
TI  - Toxicity of copper hydroxide, dithianon, fluazinam, tebuconazole and
      pyraclostrobin to Didymella applanata isolates from Serbia.
AB  - A study of the in vitro sensitivity of 10 isolates of Didymella applanata to
      copper hydroxide, dithianon, fluazinam, tebuconazole and pyraclostrobin, was
      conducted. The isolates were derived from diseased raspberry canes sampled during
      2013 at five localities in western part of Serbia, known as the main raspberry
      growing region of the country. Prior to sensitivity testing experimental
      conditions for radial growth assay were optimized. The results showed that the
      temperature of 22  degrees C, oatmeal agar medium and 12/12 hrs light/ darkness
      light regimen provided the best conditions for sensitivity tests. Most of D.
      applanata isolates were sensitive to the tested fungicides. The narrowest range
      of EC50 values was recorded for tebuconazole (1.42-2.66 mg L(-1)). The widest
      range of EC50 values was obtained for pyraclostrobin, ranging from 0.17 mg L(-1)
      to 55.33 mg L(-1). The EC50 values for the studied isolates were 39.48-51.19 mg
      L(-1) for copper hydroxide, 12.12-18.73 mg L(-1) for dithianon and 5.72-42.56 mg
      L(-1) for fluazinam. According to resistance factor values, all D. applanata
      isolates were sensitive to copper hydroxide, dithianon and tebuconazole. Among
      tested isolates, six were highly resistant to pyraclostrobin (RFs in the range of
      207.1-325.5) and two moderately resistant to fluazinam (RFs were 3 and 7.4),
      respectively.

PMID- 25602151
TI  - Structural changes in soil communities after triclopyr application in soils
      invaded by Acacia dealbata Link.
AB  - Triclopyr is a commonly used herbicide in the control of woody plants and can
      exhibit toxic effects to soil microorganisms. However, the impact on soils
      invaded by plant exotics has not yet been addressed. Here, we present the results
      of an 18-month field study conducted to evaluate the impact of triclopyr on the
      structure of fungal and bacterial communities in soils invaded by Acacia dealbata
      Link, through the use of denature gradient gel electrophoresis. After triclopyr
      application, analyses of bacterial fingerprints suggested a change in the
      structure of the soil bacterial community, whereas the structure of the soil
      fungal community remained unaltered. Bacterial density and F:B ratio values
      changed across the year but were not altered due to herbicide spraying. On the
      contrary, fungal diversity was increased in plots sprayed with triclopyr 5 months
      after the first application. Richness and diversity (H') of both bacteria and
      fungi were not modified after triclopyr application.

PMID- 25602152
TI  - Winery vermicomposts to control the leaching of diuron, imidacloprid and their
      metabolites: role of dissolved organic carbon content.
AB  - Soil organic amendment addition is an effective practice in Mediterranean areas
      due to its associated high agricultural benefits and its potential to reduce the
      pesticide impact on water resources. However, their metabolites have received
      scarce attention, even when they may pose more risk than their parent compounds.
      Two winery vermicomposts obtained from spent grape marc (V1) and the mixture vine
      shoot-biosolid vinasses (V2) have been investigated as low cost organic
      amendments to minimize the leaching of diuron, imidacloprid and their metabolites
      in columns packed with a sandy loam (S1) and a silty-clay loam soil (S2) under
      steady state flow conditions. In the unamended soil columns, leached amounts of
      diuron were 75% and 53% in S1 and S2, respectively. Its metabolites (3-(3,4
      dichlorophenyl)-1-methylurea, DPMU; and 3,4-dichlorophenylurea, DPU) percolated
      less than 35% of the total applied amount. The amount of the metabolite 3,4
      dichloroaniline (DCA) was 2% and 30% for S1 and S2, respectively. Leaching of
      imidacloprid was 79% and 96% for S1 and S2, respectively, while its metabolite 6
      chloronicotinic acid (CNA) was entirely leached. In the vermicompost-amended
      columns, the leaching of diuron was reduced 2 to 3-fold. DPMU and DPU were also
      significantly reduced (more than 6-fold). DCA did not appear in any of the
      leachates of the amended soil columns. Imidacloprid leaching was reduced 1 to 2
      folds in the amended columns. The amendments did not affect the transport of CNA.
      The dissolved organic carbon (DOC) from the vermicomposts did not enhance
      pesticide transport throughout the soil in any case. This qualitative study
      presents these vermicomposts as an effective potential low-cost tool in reducing
      pesticide and metabolite leaching. The next step would be to test them under more
      realistic conditions. 

PMID- 25602153
TI  - Changes in antioxidant status of porcine ovarian granulosa cells after quercetin
      and T-2 toxin treatment.
AB  - The aim of this study was to determine the activity of superoxide dismutase
      (SOD), glutathione peroxidase (GPx), production of reactive oxygen species (ROS),
      and total antioxidant status (TAS) in porcine ovarian granulosa cells after
      quercetin and T-2 toxin exposure in vitro. Porcine ovarian granulosa cells were
      incubated with quercetin and T-2 toxin separately or in mutual combination at the
      doses of 1 ng/mL, 10 ng/mL, 100 ng/mL, and the control group without any
      additions for 24 h. In this study T-2 toxin developed stress reaction in porcine
      ovarian granulosa cells and increased generation of ROS. Quercetin had no effect
      in elimination of ROS generation induced by T-2 toxin, but was effective in
      maintaining and increasing of TAS, activities of SOD and GPx in porcine granulosa
      cells in vitro. These results contribute towards the understanding of cellular
      stress and its response.

PMID- 25602154
TI  - Bioaccumulation of elements in three selected mushroom species from southwest
      Poland.
AB  - The contents of 16 minerals and trace elements (Ag, As, Ca, Cd, Co, Cr, Cu, Fe,
      Hg, Mg, Mn, Ni, Pb, Pt, Ti and Zn) were analyzed in edible mushrooms (Leccinum
      scabrum, Boletus edulis and Boletus badius) collected in southwest Poland.
      Content of Co, Ni and Pb was similar in all tested mushroom species, while
      content of Ag, Ca, Cd, Hg and Ti was significantly higher in B. edulis than in L.
      scabrum and B. badius. The largest differences between these species were
      observed for Fe and Zn accumulation. The highest contents of these elements were
      noted in B. badius bodies (202 +/- 88 and 137 +/- 24 mg kg(-1) dry matter,
      respectively), lower in B. edulis (131 +/- 99 and 89 +/- 26 mg kg(-1) dry matter,
      respectively) and lowest in L. scabrum. Differences in As, Cu and Cr content
      between tested species were observed mainly between L. scabrum and B. badius
      fruiting bodies. Content of Pt was below 0.01 mg kg(-1) dry matter). In the case
      of Mg and Mn accumulation, differences between B. edulis and B. badius were not
      observed (478 and 440 mg kg(-1) dry matter for Mg and 23 and 19 mg kg(-1) dry
      matter for Mn), and the results showed significantly higher content of these
      elements than in L. scabrum bodies (312 and 10 mg kg(-1) dry matter,
      respectively). It is worth underlining that clear accumulation shown by the
      bioconcentration factor (BCF>1) observed for all three mushroom species was noted
      in the case of elements Ag, Cd, Co, Cu, Hg, Ni and Zn only.

PMID- 25602155
TI  - Evaluation of anaerobic co-digestion of dairy manure with food wastes via bio
      methane potential assay and CSTR reactor.
AB  - The introduction of food wastes into anaerobic digestion (AD) brings a promising
      scenario of increasing feedstock availability and overall energy production from
      AD. This study evaluated the biodegradability and methane potential from co
      digestion of two typical food wastes, kitchen waste and chicken fat, with dairy
      manure. For single substrate, the bio-methane potential assays showed that
      kitchen waste had the highest methane yield of 352 L-CH4 kg(-1)-VS added, 92%
      more than dairy manure alone. Chicken fat at the same Volatile Solid (VS) level
      (2 g L(-1)) inhibited bio-methane production. Addition of kitchen waste and
      chicken fat to a VS percentage of up to 40% improved overall methane yield by 44%
      and 34%, respectively. Synergistic effect was observed when either combining two
      or three substrates as AD feedstock, possibly as a result of increased
      biodegradability of organic materials in chicken fat and kitchen waste compared
      with dairy manure. Addition of chicken fat improved methane yield more than
      kitchen waste. However, addition of chicken fat VS over 0.8 g L(-1) should be
      cautiously done because it may cause reactor failure due to decrease in pH. The
      maximum methane yield was 425 L-CH4 kg(-1)-VS, achieved at a VS ratio of 2:2:1
      for kitchen waste, chicken fat, and dairy manure. Results from batch AD
      experiment demonstrated that supplementing dairy manure to chicken fat and/or
      kitchen waste improved alkalinity of substrate due to the inclusion of more
      titratable bases in dairy manure, and therefore stabilized the methanogenesis and
      substantially improved biogas yield. A mixture of substrates of kitchen waste,
      chicken fat, and dairy manure at a ratio of 1:1:3 was fed to a continuously
      stirred tank reactor operated at organic loading rates of 3.28, 6.55, and 2.18 g
      COD L(-1)-day (hydraulic retention time of 20, 10, and 30 days, respectively)
      under mesophilic condition, and methane production rate reached 0.65, 0.95, and
      0.34 L-CH4 L(-1)-reactor-day.

PMID- 25602156
TI  - Factor inhibiting HIF1alpha (FIH-1) functions as a tumor suppressor in human
      colorectal cancer by repressing HIF1alpha pathway.
AB  - Colorectal cancer (CRC) is one of the most common cancers worldwide. The
      molecular mechanisms underlying CRC development involve a multistep process with
      the accumulation of both genetic and epigenetic changes. To deeply understand CRC
      tumorigenesis and progression, advances in identification of novel mechanisms and
      key factors are therefore in an urgent need. Here, we examined the correlation of
      factor inhibiting HIF-1alpha (FIH-1) expression with clinicopathological features
      of CRC. The finding that FIH-1 was not only significantly decreased in tumor
      tissue but also was significantly correlated with tumor invading depth, lymph
      node involvement, and metastasis suggested the role of FIH-1 as a tumor
      suppressor in CRC development. To further support the above hypothesis, we
      performed both in vitro and in vivo experiments to identify the role of FIH-1 in
      CRC development. FIH-1 was found to inhibit CRC cell proliferation, migration,
      invasion, and colony formation in vitro. FIH-1 was also shown to repress LOVO
      xenograft tumor growth in vivo. To decipher the mechanism, we examined the
      expression level of HIF-1alpha and its target genes. We found that FIH-1 was able
      to inhibit HIF1alpha mediated transcription of GLUT1 and VEGF in CRC cells. The
      above observation points to the possibility that loss or decreased expression of
      FIH-1 gene may lead to a constitutive activation of HIF1alpha and an alteration
      of HIF-1 targets such as GLUT-1 and VEGF. These findings highlight the critical
      role of FIH-1 in CRC and indicate FIH-1 functions as a tumor suppressor in human
      CRC by repressing HIF1alpha pathway. 

PMID- 25602159
TI  - Rhodium nanoparticles for ultraviolet plasmonics.
AB  - The nonoxidizing catalytic noble metal rhodium is introduced for ultraviolet
      plasmonics. Planar tripods of 8 nm Rh nanoparticles, synthesized by a modified
      polyol reduction method, have a calculated local surface plasmon resonance near
      330 nm. By attaching p-aminothiophenol, local field-enhanced Raman spectra and
      accelerated photodamage were observed under near-resonant ultraviolet
      illumination, while charge transfer simultaneously increased fluorescence for up
      to 13 min. The combined local field enhancement and charge transfer demonstrate
      essential steps toward plasmonically enhanced ultraviolet photocatalysis. 

PMID- 25602158
TI  - Fibroadipose hyperplasia versus Proteus syndrome: segmental overgrowth with a
      mosaic mutation in the PIK3CA gene.

PMID- 25602157
TI  - Genetic and pharmacological analysis identifies a physiological role for the AHR
      in epidermal differentiation.
AB  - Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to
      affect epidermal differentiation and skin barrier formation. The physiological
      role of endogenous AHR signaling in keratinocyte differentiation is not known. We
      used murine and human skin models to address the hypothesis that AHR activation
      is required for normal keratinocyte differentiation. Using transcriptome analysis
      of Ahr(-/-) and Ahr(+/+) murine keratinocytes, we found significant enrichment of
      differentially expressed genes linked to epidermal differentiation. Primary Ahr(
      /-) keratinocytes showed a significant reduction in terminal differentiation gene
      and protein expression, similar to Ahr(+/+) keratinocytes treated with AHR
      antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM) SGA360.
      In vitro keratinocyte differentiation led to increased AHR levels and subsequent
      nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer
      cultured primary human keratinocytes treated with AHR antagonists also showed an
      impaired terminal differentiation program. Inactivation of AHR activity during
      human skin equivalent development severely impaired epidermal stratification,
      terminal differentiation protein expression, and stratum corneum formation. As
      disturbed epidermal differentiation is a main feature of many skin diseases,
      pharmacological agents targeting AHR signaling or future identification of
      endogenous keratinocyte-derived AHR ligands should be considered as potential new
      drugs in dermatology. 

PMID- 25602160
TI  - An improved high throughput sequencing method for studying oomycete communities.
AB  - Culture-independent studies using next generation sequencing have revolutionized
      microbial ecology, however, oomycete ecology in soils is severely lagging behind.
      The aim of this study was to improve and validate standard techniques for using
      high throughput sequencing as a tool for studying oomycete communities. The well
      known primer sets ITS4, ITS6 and ITS7 were used in the study in a semi-nested PCR
      approach to target the internal transcribed spacer (ITS) 1 of ribosomal DNA in a
      next generation sequencing protocol. These primers have been used in similar
      studies before, but with limited success. We were able to increase the proportion
      of retrieved oomycete sequences dramatically mainly by increasing the annealing
      temperature during PCR. The optimized protocol was validated using three mock
      communities and the method was further evaluated using total DNA from 26 soil
      samples collected from different agricultural fields in Denmark, and 11 samples
      from carrot tissue with symptoms of Pythium infection. Sequence data from the
      Pythium and Phytophthora mock communities showed that our strategy successfully
      detected all included species. Taxonomic assignments of OTUs from 26 soil sample
      showed that 95% of the sequences could be assigned to oomycetes including
      Pythium, Aphanomyces, Peronospora, Saprolegnia and Phytophthora. A high
      proportion of oomycete reads was consistently present in all 26 soil samples
      showing the versatility of the strategy. A large diversity of Pythium species
      including pathogenic and saprophytic species were dominating in cultivated soil.
      Finally, we analyzed amplicons from carrots with symptoms of cavity spot. This
      resulted in 94% of the reads belonging to oomycetes with a dominance of species
      of Pythium that are known to be involved in causing cavity spot, thus
      demonstrating the usefulness of the method not only in soil DNA but also in a
      plant DNA background. In conclusion, we demonstrate a successful approach for
      pyrosequencing of oomycete communities using ITS1 as the barcode sequence with
      well-known primers for oomycete DNA amplification. 

PMID- 25602162
TI  - Cytochrome P450 1A2 co-determines neuroleptic load and may diminish tardive
      dyskinesia by increased inducibility.
AB  - OBJECTIVES: The aim of this study was to investigate a possible association
      between tardive dyskinesia (TD) and CYP1A2 (*1F, -163C>A, rs762551) polymorphism
      in Russian psychiatric inpatients. METHODS: TD was assessed cross-sectionally
      using the Abnormal Involuntary Movement Scale (AIMS). Orofacial and limb-truncal
      dyskinesia were assessed with AIMS 1-4 and 5-7, respectively. Standard protocols
      were applied for genotyping. Analysis of covariance (ANCOVA) was used to compare
      the mean AIMS scores for each of the genotypic classes. RESULTS: A total of 319
      Caucasian patients from West Siberia with schizophrenia and 117 healthy
      volunteers were investigated. No significant differences between the patients and
      the controls in genotype frequencies were found. Analysis of covariance (ANCOVA)
      with age, sex, duration of disease, chlorpromazine equivalent (CPZEQ)
      incorporated as covariates showed that limb-truncal, but not orofacial TD, is
      associated with CYP1A2 (-163C>, rs762551) polymorphism (F = 3.27, P = 0.039).
      Patients with the C/C genotype had a higher mean AIMS 5-7 score than those with
      the A/C or the A/A genotype. CONCLUSIONS: Our results support the hypothesis that
      not only with clozapine, but also with other classical and atypical
      antipsychotics, smoking may decrease plasma levels; this is most extensively
      expressed in carriers of the CYP1A2*1F (-163C> A) polymorphism.

PMID- 25602161
TI  - Differential specificity of selective culture media for enumeration of pathogenic
      vibrios: advantages and limitations of multi-plating methods.
AB  - Plating environmental samples on vibrio-selective chromogenic media is a commonly
      used technique that allows one to quickly estimate concentrations of putative
      vibrio pathogens or to isolate them for further study. Although this approach is
      convenient, its usefulness depends directly on how well the procedure selects
      against false positives. We tested whether a chromogenic medium, CHROMagar Vibrio
      (CaV), used alone (single-plating) or in combination (double-plating) with a
      traditional medium thiosulfate-citrate-bile-salts (TCBS), could improve the
      discrimination among three pathogenic vibrio species (Vibrio cholerae, Vibrio
      parahaemolyticus, and Vibrio vulnificus) and thereby decrease the number of false
      positive colonies that must be screened by molecular methods. Assays were
      conducted on water samples from two estuarine environments (one subtropical, one
      tropical) in a variety of seasonal conditions. The results of the double-plating
      method were confirmed by PCR and 16S rRNA sequencing. Our data indicate that
      there is no significant difference in the false-positive rate between CaV and
      TCBS when using a single-plating technique, but determining color changes on the
      two media sequentially (double-plating) reduced the rate of false positive
      identification in most cases. The improvement achieved was about two-fold on
      average, but varied greatly (from 0- to 5-fold) and depended on the sampling time
      and location. The double-plating method was most effective for V. vulnificus in
      warm months, when overall V. vulnificus abundance is high (false positive rates
      as low as 2%, n=178). Similar results were obtained for V. cholerae (minimum
      false positive rate of 16%, n=146). In contrast, the false positive rate for V.
      parahaemolyticus was always high (minimum of 59%, n=109). Sequence analysis of
      false-positive isolates indicated that the majority of confounding isolates are
      from the Vibrionaceae family, however, members of distantly related bacterial
      groups were also able to grow on vibrio-selective media, even when using the
      double-plating method. In conclusion, the double-plating assay is a simple means
      to increase the efficiency of identifying pathogenic vibrios in aquatic
      environments and to reduce the number of molecular assays required for identity
      confirmation. However, the high spatial and temporal variability in the
      performance of the media mean that molecular approaches are still essential to
      obtain the most accurate vibrio abundance estimates from environmental samples. 

PMID- 25602163
TI  - Two Phase III randomised double-blind studies of fixed-dose TC-5214
      (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with
      major depressive disorder and an inadequate response to prior antidepressant
      therapy.
AB  - OBJECTIVES: To evaluate the neuronal nicotinic channel modulator TC-5214
      (dexmecamylamine) as adjunct therapy in patients with major depressive disorder
      (MDD) and inadequate response to prior antidepressant treatment. METHODS: Study
      004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label
      antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised,
      active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or
      4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy
      endpoint was change in MADRS total score from randomisation (Week 8) to treatment
      end (Week 16). Secondary endpoints included MADRS response and remission, and
      changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored
      throughout. RESULTS: Studies 004 and 005 randomised 640 and 696 patients,
      respectively, to TC-5214 or placebo. No statistically significant improvements in
      MADRS total score or any secondary endpoints were seen with TC-5214 versus
      placebo in either study at treatment end. The most commonly reported adverse
      events (> 10%) with TC-5214 were constipation, dizziness and dry mouth.
      CONCLUSIONS: TC-5214 adjunct to antidepressant was generally well tolerated.
      However, the studies were not supportive of an antidepressant effect for TC-5214
      in patients with MDD and inadequate response to prior antidepressant therapy.

PMID- 25602165
TI  - Platelets: the end of an era, start of a new beginning.

PMID- 25602164
TI  - Lipid extract from hard-shelled mussel (Mytilus coruscus) improves clinical
      conditions of patients with rheumatoid arthritis: a randomized controlled trial.
AB  - Studies have suggested a lipid extract from hard-shelled mussel (Mytilus
      coruscus) (HMLE) possessed strong anti-inflammatory activity in arthritis model
      of rats. This study investigated whether HMLE could improve clinical conditions
      of rheumatoid arthritis patients. Fifty rheumatoid arthritis patients (28-75
      years) were randomly assigned to receive HMLE capsules or receive placebo
      capsules for 6 months. Forty-two subjects and 50 subjects were included in per
      protocol and intention-to-treat analysis, respectively. Significant differences
      in changes on disease activity score (DAS28) and clinical disease activity index
      (CDAI) after 6-month intervention (p < 0.01) were observed in both analyses with
      more evident efficacy shown in per-protocol population (?DAS28 = 0.47; ?CDAI =
      4.17), which favored the benefits of the HMLE group. TNF-alpha (tumor necrosis
      factor alpha), interleukin (IL)-1beta and PGE2 (prostaglandin E2) but not IL-6,
      were significantly decreased in both groups, and the decrements were much larger
      in the HMLE group for TNF-alpha and PGE2 after 6 months from baseline (p < 0.05).
      IL-10 was significantly increased in both groups and the change was much more
      evident in the HMLE group (p < 0.05). In conclusion, HMLE exhibited benefits for
      the clinical conditions of rheumatoid patients in relation to improvement in the
      balance between pro- and anti-inflammatory factors, which indicated its potential
      to serve as adjunctive treatment for rheumatoid arthritis. (ClinicalTrials.gov
      NCT02173587). 

PMID- 25602166
TI  - Multidisciplinary ALS clinics in the USA: A comparison of those who attend and
      those who do not.
AB  - Optimization of quality of life (QoL) is perceived by many as the primary goal
      for patients with amyotrophic lateral sclerosis (ALS), often via
      multidisciplinary clinics (MDCs). The aim of this study was to examine the
      differences in QoL, physical function, and social problem-solving skills for
      individuals with ALS attending MDCs compared to non-attenders. An online survey
      was completed by 295 people with ALS in the United States. Results showed there
      were no differences between the groups in global QoL, measures of physical
      function, or social problem-solving skills. Attenders and non-attenders of MDCs
      reported similar use of treatments for their ALS, although attenders received
      more health care services from nurses, therapists, social workers, dieticians,
      and in-home care providers. In conclusion, oher instruments may be needed to
      assess the benefits of MDCs. Qualitative studies of attenders and non-attenders
      of MDCs may reveal important differences that could guide care. 

PMID- 25602167
TI  - Zn3P2-Zn3As2 solid solution nanowires.
AB  - Semiconductor alloy nanowires (NWs) have recently attracted considerable
      attention for applications in optoelectronic nanodevices because of many notable
      properties, including band gap tunability. Zinc phosphide (Zn3P2) and zinc
      arsenide (Zn3As2) belong to a unique pseudocubic tetragonal system, but their
      solid solution has rarely been studied. Here In this study, we synthesized
      composition-tuned Zn3(P1-xAsx)2 NWs with different crystal structures by
      controlling the growth conditions during chemical vapor deposition. A first type
      of synthesized NWs were single-crystalline and grew uniformly along the [110]
      direction (in a cubic unit cell) over the entire compositional range (0 <= x <=
      1) explored. The use of an indium source enabled the growth of a second type of
      NWs, with remarkable cubic-hexagonal polytypic twinned superlattice and
      bicrystalline structures. The growth direction of the Zn3P2 and Zn3As2 NWs was
      also switched to [111] and [112], respectively. These structural changes are
      attributable to the Zn-depleted indium catalytic nanoparticles which favor the
      growth of hexagonal phases. The formation of a solid solution at all compositions
      allowed the continuous tuning of the band gap (1.0-1.5 eV). Photocurrent
      measurements were performed on individual NWs by fabricating photodetector
      devices; the single-crystalline NWs with [110] growth direction exhibit a higher
      photoconversion efficiency compared to the twinned crystalline NWs with [111] or
      [112] growth direction. 

PMID- 25602168
TI  - Salivary alpha-amylase and cortisol after exercise in menopause: influence of
      long-term HRT.
AB  - OBJECTIVES: This observational prospective study analyzed the effect of an
      incremental cardiopulmonary exercise test (CPET) on the secretion of salivary
      biomarkers of the adrenergic nervous system and hypothalamus-pituitary-adrenal
      (HPA) axis activity by measuring salivary alpha-amylase and cortisol diurnal
      trajectories in the setting of long-term hormone replacement therapy (HRT).
      METHODS: Fifteen healthy sedentary postmenopausal women who were current HRT
      users and 15 women who had never used HRT were consecutively recruited. alpha
      Amylase and cortisol were measured in salivary samples collected on the CPET day
      and on a rest day. Cardiovascular and respiratory fitness parameters were
      recorded during the CPET challenge. RESULTS: The participants had very
      homogeneous somatic characteristics, and they were all in generally good health.
      The postmenopausal never-HRT users presented an abnormal diurnal pattern of alpha
      amylase at baseline and a flattened response to CPET. In contrast, women on HRT
      had a physiological alpha-amylase diurnal pattern and increased salivary alpha
      amylase production during the CPET-induced challenge. The CPET challenge
      physiologically activated the HPA axis activity, as shown by the increase in the
      concentration of salivary cortisol during the effort test. HPA axis activity was
      not affected by long-term HRT. Postmenopausal women using HRT exhibited a
      cardiorespiratory functional capacity that was significantly (p < 0.05) higher
      than that of non-users. CONCLUSIONS: Our findings show that healthy
      postmenopausal women present an asymmetry between adrenergic nervous system and
      HPA axis activities under both basal and stress conditions. HRT was able to
      modify the abnormal adrenergic nervous system activity, most likely by reducing
      the sympathetic hyperactivity that characterizes menopause.

PMID- 25602169
TI  - Yeast-based high-throughput screen identifies Plasmodium falciparum equilibrative
      nucleoside transporter 1 inhibitors that kill malaria parasites.
AB  - Equilibrative transporters are potential drug targets; however, most functional
      assays involve radioactive substrate uptake that is unsuitable for high
      throughput screens (HTS). We developed a robust yeast-based growth assay that is
      potentially applicable to many equilibrative transporters. As proof of principle,
      we applied our approach to Equilibrative Nucleoside Transporter 1 of the malarial
      parasite Plasmodium falciparum (PfENT1). PfENT1 inhibitors might serve as novel
      antimalarial drugs since PfENT1-mediated purine import is essential for parasite
      proliferation. To identify PfENT1 inhibitors, we screened 64 560 compounds and
      identified 171 by their ability to rescue the growth of PfENT1-expressing
      fui1Delta yeast in the presence of a cytotoxic PfENT1 substrate, 5-fluorouridine
      (5-FUrd). In secondary assays, nine of the highest activity compounds inhibited
      PfENT1-dependent growth of a purine auxotrophic yeast strain with adenosine as
      the sole purine source (IC50 0.2-2 MUM). These nine compounds completely blocked
      [(3)H]adenosine uptake into PfENT1-expressing yeast and erythrocyte-free
      trophozoite-stage parasites (IC50 5-50 nM), and inhibited chloroquine-sensitive
      and -resistant parasite proliferation (IC50 5-50 MUM). Wild-type (WT) parasite
      IC50 values were up to 4-fold lower compared to PfENT1-knockout (pfent1Delta)
      parasites. pfent1Delta parasite killing showed a delayed-death phenotype not
      observed with WT. We infer that, in parasites, the compounds inhibit both PfENT1
      and a secondary target with similar efficacy. The secondary target identity is
      unknown, but its existence may reduce the likelihood of parasites developing
      resistance to PfENT1 inhibitors. Our data support the hypothesis that blocking
      purine transport through PfENT1 may be a novel and compelling approach for
      antimalarial drug development.

PMID- 25602170
TI  - The Adolescent Behavioral Activation Program: Adapting Behavioral Activation as a
      Treatment for Depression in Adolescence.
AB  - This study aimed to examine implementation feasibility and initial treatment
      outcomes of a behavioral activation (BA) based treatment for adolescent
      depression, the Adolescent Behavioral Activation Program (A-BAP). A randomized,
      controlled trial was conducted with 60 clinically referred adolescents with a
      depressive disorder who were randomized to receive either 14 sessions of A-BAP or
      uncontrolled evidenced-based practice for depression. The urban sample was 64%
      female, predominantly Non-Hispanic White (67%), and had an average age of 14.9
      years. Measures of depression, global functioning, activation, and avoidance were
      obtained through clinical interviews and/or through parent and adolescent self
      report at preintervention and end of intervention. Intent-to-treat linear mixed
      effects modeling and logistic regression analysis revealed that both conditions
      produced statistically significant improvement from pretreatment to end of
      treatment in depression, global functioning, and activation and avoidance. There
      were no significant differences across treatment conditions. These findings
      provide the first step in establishing the efficacy of BA as a treatment for
      adolescent depression and support the need for ongoing research on BA as a way to
      enhance the strategies available for treatment of depression in this population. 

PMID- 25602171
TI  - Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic
      inflammation and lipid accumulation through NLRP3 inflammasome activation.
AB  - AIMS: Increased fructose consumption predisposes the liver to nonalcoholic fatty
      liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting
      protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain
      containing 3 (NLRP3) inflammasome activation and this signaling axis may be
      involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen
      species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3
      inflammasome activation, inflammation, and lipid accumulation. RESULTS: Rats were
      fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin
      during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes
      (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2)
      were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP
      or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and
      pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers
      and activators of transcription 3-mediated inflammatory signaling, and expression
      alteration of lipid metabolism-related genes in cultured hepatocytes and rat
      livers. NLRP3 silencing and caspase-1 suppression blocked these effects in
      primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters
      hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in
      animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation,
      inflammation, and lipid metabolism perturbations but not ROS induction in
      fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP
      induction and diminished the detrimental effects in fructose-exposed hepatocytes
      and rat livers. INNOVATION AND CONCLUSIONS: This study provides a novel mechanism
      for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates
      hepatocellular NLRP3 inflammasome activation, inflammation and lipid
      accumulation. Antioxidant-based interventions can inhibit the ROS-TXNIP pathway.

PMID- 25602172
TI  - Identification as overweight by medical professionals: relation to eating
      disorder diagnosis and risk.
AB  - PURPOSE: Discussions about weight between medical professionals and young adults
      may increase risk of eating disorders (EDs). Clarifying the relation between
      screening for overweight and ED risk is needed. METHODS: 548 college-age women
      were classified as at-risk (n=441) or with an ED (n=107), and were assessed for
      disordered eating attitudes, behaviors, and relevant history, including, "Has a
      doctor, nurse, or other medical professional ever told you that you were
      overweight?" Regression analyses were used to evaluate the relations between
      being identified as overweight and current disordered eating behaviors,
      attitudes, and ED diagnosis, without and with covariates (history of weight
      related teasing, history of an ED, family history of being identified as
      overweight, and current body mass index). RESULTS: 146 (26.6%) women reported
      being previously identified as overweight by a medical professional. There was no
      relation between being previously identified as overweight and having an ED.
      Those identified as overweight were more likely to have weight/shape concerns
      above a high-risk cutoff, but showed no difference in dietary restraint, binge
      eating, purging behaviors, or excessive exercise compared to those not
      identified. CONCLUSIONS: Being previously identified as overweight by a medical
      professional was associated with increased weight/shape concerns but not with
      current disordered eating behaviors or ED status. Minimizing the potential
      negative effects of overweight screening on weight and shape concerns by
      providing patients with strategies to increase healthy lifestyle behaviors and
      long-term support for healthy weight loss goals may have a positive impact on
      reducing the public health problem of overweight and obesity.

PMID- 25602174
TI  - Quality of life in pediatric patients affected by electrophysiologic disease.
AB  - BACKGROUND: Treatment of electrophysiologic (EP) disease in pediatric patients
      has improved; however, the effects on quality of life (QOL) are unknown.
      OBJECTIVE: The purpose of this study was to compare QOL within EP disease groups
      and to other congenital heart diseases, to evaluate the effects of cardiac rhythm
      devices on QOL, and to identify drivers of QOL in EP disease. METHODS: Cross
      sectional study of patient/parent proxy-reported Pediatric Cardiac Quality of
      Life Inventory scores (Total, Disease Impact, Psychosocial Impact) in subjects
      aged 8 to 18 years from 11 centers with congenital complete heart block (CCHB),
      ventricular tachycardia (VT), supraventricular tachycardia (SVT), and long QT
      syndrome (LQTS). QOL was compared between EP disease groups and congenital heart
      disease groups [bicuspid aortic valve (BAV), tetralogy of Fallot (TOF), and
      Fontan]. General linear modeling was used to perform group comparisons and to
      identify predictors of QOL variation. RESULTS: Among 288 patient-parent pairs,
      mean age was 12.8 +/- 3.0 years. CCHB (MU = 83) showed higher patient Total QOL
      than other EP disease cohorts (P <= .02; LQTS MU = 73; SVT MU = 74). SVT (MU =
      75) and LQTS (MU = 75) had lower patient Total scores than BAV (MU = 81; P <=
      .008). Patient/parent-proxy QOL scores for all EP disease groups were not
      different than TOF and higher than Fontan. The presence of a cardiac rhythm
      device was associated with lower QOL scores in LQTS (MU = 66 vs MU = 76; P <
      .01). Predictors of lower patient/parent-proxy QOL included EP disease type (P <=
      .03), increased medical care utilization (P <= .04), and no parental college
      degree (P <= .001). CONCLUSION: Given the significant variation in QOL in EP
      disease type, stratification by EP disease type and increased medical care
      utilization may allow for targeted interventions to improve QOL.

PMID- 25602173
TI  - Serial measures of cardiac troponin T levels by a highly sensitive assay and
      incident atrial fibrillation in a prospective cohort of ambulatory older adults.
AB  - BACKGROUND: Various mechanisms in cardiac remodeling related to atrial
      fibrillation (AF) lead to elevated circulating cardiac troponin levels, but
      little is known about such elevations upstream to AF onset. OBJECTIVE: The
      purpose of this study was to study the association between circulating troponin
      levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and
      incident atrial fibrillation (AF). METHODS: In a large prospective cohort of
      ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels
      were measured in sera that were collected at enrollment from 4262 participants
      without AF (2871 with follow-up measurements). Incident AF was identified by
      electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare
      files, including outpatient and physician claims diagnoses. RESULTS: Over median
      follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0%)
      developed AF. Higher baseline levels of hs-cTnT were associated with incident AF
      in covariate-adjusted analyses accounting for demographics, traditional risk
      factors, and incident heart failure in time-dependent analyzes (hazard ratio for
      3rd tertile vs undetectable 1.75, 95% confidence interval 1.48-2.08). This
      association was statistically significant in analyses that additionally adjusted
      for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd
      tertile vs undetectable 1.38, 95% confidence interval 1.16-1.65). Significant
      associations were also found when hs-cTnT levels were treated as a continuous
      variable and when examining change from baseline of hs-cTnT levels and incident
      AF. CONCLUSION: The findings show a significant association of circulating
      troponin levels in ambulatory older adults with incident AF beyond that of
      traditional risk factors, incident heart failure, and biomarkers of inflammation
      and hemodynamic strain.

PMID- 25602176
TI  - Characterising human atherosclerotic carotid plaque tissue composition and
      morphology using combined spectroscopic and imaging modalities.
AB  - Calcification is a marked pathological component in carotid artery plaque.
      Studies have suggested that calcification may induce regions of high stress
      concentrations therefore increasing the potential for rupture. However, the
      mechanical behaviour of the plaque under the influence of calcification is not
      fully understood. A method of accurately characterising the calcification coupled
      with the associated mechanical plaque properties is needed to better understand
      the impact of calcification on the mechanical behaviour of the plaque during
      minimally invasive treatments. This study proposes a comparison of biochemical
      and structural characterisation methods of the calcification in carotid plaque
      specimens to identify plaque mechanical behaviour. Biochemical analysis, by
      Fourier Transform Infrared (FTIR) spectroscopy, was used to identify the key
      components, including calcification, in each plaque sample. However, FTIR has a
      finite penetration depth which may limit the accuracy of the calcification
      measurement. Therefore, this FTIR analysis was coupled with the identification of
      the calcification inclusions located internally in the plaque specimen using
      micro x-ray computed tomography (MUX-CT) which measures the calcification volume
      fraction (CVF) to total tissue content. The tissue characterisation processes
      were then applied to the mechanical material plaque properties acquired from
      experimental circumferential loading of human carotid plaque specimen for
      comparison of the methods. FTIR characterised the degree of plaque progression by
      identifying the functional groups associated with lipid, collagen and
      calcification in each specimen. This identified a negative relationship between
      stiffness and 'lipid to collagen' and 'calcification to collagen' ratios.
      However, MUX-CT results suggest that CVF measurements relate to overall
      mechanical stiffness, while peak circumferential strength values may be dependent
      on specific calcification geometries. This study demonstrates the need to fully
      characterise the calcification structure of the plaque tissue and that a
      combination of FTIR and MUX-CT provides the necessary information to fully
      understand the mechanical behaviour of the plaque tissue.

PMID- 25602177
TI  - Re: Antiplatelet and Anticoagulative Medication During Shockwave Lithotripsy.

PMID- 25602178
TI  - Molecular organization of nalidixate conjugated calixarenes in bacterial model
      membranes probed by molecular dynamics simulation and Langmuir monolayer studies.
AB  - Two p-tert-butylcalix[4]arene derivatives bearing one or two nalidixic acid
      groups connected to the lower rim of p-tert-butylcalix[4]arene through the
      propylenic spacer were studied upon interaction with model bacterial membranes.
      Indeed, these derivatives were developed recently as new macrocyclic antibiotic
      carriers for antibacterial therapy. To obtain molecular level information about
      the interaction between the calixarene conjugates and a membrane lipid, atomistic
      molecular dynamics simulation, as well as surface pressure, surface potential,
      polarization modulation infrared reflection-absorption spectroscopy, and Brewster
      angle microscopy studies of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine
      (DMPE)-calixarene derivative films were performed. The results obtained indicate
      that the interaction between the calixarene derivatives and DMPE occurs via the
      phosphate and carbonyl groups present in the lipid. Although both calixarene
      derivatives increase the chain tilt and conformational disordering of the DMPE
      molecules, these effects are more important in the case of the monosubstituted
      derivative. Importantly, the two derivatives have an opposite impact on hydration
      of the phosphoglyceride polar head. 

PMID- 25602179
TI  - Gluten-free diet in the management of patients with irritable bowel syndrome,
      fibromyalgia and lymphocytic enteritis.
AB  - An evaluation of the effect of 1 year of a gluten-free diet was performed in
      patients with irritable bowel syndrome and fibromyalgia syndrome displaying
      lymphocytic enteritis. Gluten withdrawal produced a slight but significant
      improvement of the functional symptoms, suggesting that gluten might be partly
      responsible for this clinical picture. This hypothesis should be confirmed by a
      double-blind placebo-controlled trial since it cannot be ruled out that the
      studied patients displayed a subjective sensation of improvement due to the
      placebo effect of gluten withdrawal. Further investigations are needed before
      recommending gluten withdrawal in patients with fibromyalgia and lymphocytic
      enteritis. 

PMID- 25602175
TI  - Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging
      RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL
      CardiOversion) study.
AB  - BACKGROUND: Currently available antiarrhythmic agents for the treatment of atrial
      fibrillation (AF) have important limitations, leaving an unmet need for safe and
      effective therapy. Ranolazine is an approved antianginal agent with a favorable
      safety profile and electrophysiologic properties suggesting a potential role in
      the treatment of AF. OBJECTIVE: The purpose of this study was to assess the
      safety and efficacy of ranolazine in the prevention of AF recurrence after
      successful electrical cardioversion and to ascertain the most appropriate dose of
      this agent. METHODS: This prospective, multicenter, randomized, double-blind,
      placebo-control parallel group phase II dose-ranging trial randomized patients
      with persistent AF (7 days to 6 months) 2 hours after successful electrical
      cardioversion to placebo, or ranolazine 375 mg, 500 mg, or 750 mg bid. Patients
      were monitored daily by transtelephonic ECG. The primary end-point was the time
      to first AF recurrence. RESULTS: Of 241 patients randomized, 238 took at least 1
      drug dose. Ranolazine proved to be safe and tolerable. No dose of the drug
      significantly prolonged time to AF recurrence. AF recurred in 56.4%, 56.9%,
      41.7%, and 39.7% of patients in the placebo, ranolazine 375 mg, ranolazine 500
      mg, and ranolazine 750 mg groups, respectively. The reduction in overall AF
      recurrence in the combined 500-mg and 750-mg groups was of borderline
      significance compared to the placebo group (P = .053) and significant compared to
      375-mg group (P = .035). CONCLUSION: No dose of ranolazine significantly
      prolonged time to AF recurrence. However, the 500-mg and 750 mg-groups combined
      reduced AF recurrences, suggesting a possible role for this agent in the
      treatment of AF.

PMID- 25602180
TI  - Psychotherapy: process, mechanisms, and science-practice integration.
AB  - I received the Early Career Award from Division 29 and the American Psychological
      Foundation in 2013. In this article, I briefly review some of my research areas,
      relevant issues, and future directions. Specifically, I focus on 3 core research
      areas: psychotherapy process-outcome, psychotherapy integration, and science
      practice integration. Within each of these core areas, I also touch on important
      methodological issues. In addition, I argue that progress in the field will
      require the application of diverse research methods, spanning basic and applied
      areas, as well as interdisciplinary and interinstitutional collaboration.

PMID- 25602181
TI  - Misinterpreting eyewitness expressions of confidence: The featural justification
      effect.
AB  - How do we know eyewitness statements of confidence are interpreted accurately by
      others? When eyewitnesses provide a verbal expression of confidence about a
      lineup identification, such as I'm fairly certain it's him, how well do others
      understand the intended meaning of this statement of confidence? And, how is this
      perception of the meaning influenced by justifications of the level of
      confidence, such as when eyewitnesses say, I remember his chin? The answers to
      these questions are unknown, as there is no research on how others interpret the
      intended meaning of eyewitness confidence. Three experiments show that an
      additional justification of confidence, relative to seeing a confidence statement
      alone, can increase misunderstanding in others' estimation of the meaning of the
      expression of confidence. Moreover, this justification-induced increase in
      misunderstanding only occurs when the justification refers to an observable
      facial feature and not when it refers to an unobservable quality (e.g., He is
      very familiar). Even more noteworthy, both Experiments 2 and 3 show that this
      featural justification effect is strongest when eyewitnesses express absolute
      certainty in an identification, such as by stating I am positive. When a highly
      confident assertion is accompanied by a featural justification others will be
      most likely to misinterpret the intended meaning.

PMID- 25602182
TI  - The world is not fair: an examination of innocent and guilty suspects' waiver
      decisions.
AB  - Suspects' decisions to waive or invoke their interrogation rights can have a
      considerable impact on their eventual legal fate. Although innocent and guilty
      suspects show differences in waiver rates, research has yet to examine whether
      innocent and guilty individuals' waiver decisions are differentially influenced
      by dispositional and situational factors. The current research examined the
      relationship among a dispositional factor (just world beliefs), a situational
      factor (social proof pressures-i.e., influencing others to believe that certain
      behaviors are normative) and innocent and guilty individuals' waiver decisions.
      Social proof pressures influenced the preinterrogation decisions of guilty
      individuals holding strong just world beliefs but not guilty individuals holding
      weak just world beliefs. However, social proof pressures influenced the
      preinterrogation decisions of innocent individuals holding weak just world
      beliefs but not innocent individuals holding strong just world beliefs. Results
      also indicated that strong just world beliefs are associated with attenuated
      stress responses to an accusation among innocent individuals but exacerbated
      stress responses among guilty individuals, thereby helping to explain why guilty
      and innocent individuals are differentially influenced by situational and
      dispositional factors. The theoretical and applied implications of these effects
      are discussed with an emphasis on the consequences of suspects' mindset during
      the preinterrogation decision-making process.

PMID- 25602185
TI  - Hailey-Hailey disease improved by fractional CO2 laser.
AB  - Hailey-Hailey disease (HHD), also known as benign familial pemphigus, is an
      autosomal dominant skin condition that affects the adhesion of epidermal
      keratinocytes. Although the initial manifestation of flaccid vesicles on
      erythematous or normal skin in flexure sites frequently goes unnoticed, large,
      macerated, exudative plaques of superficial erosions with crusting are observed
      at the time of diagnosis. There is no specific treatment for HHD, and most cases
      are symptomatically supported. However, infrared laser ablation has been somewhat
      helpful. We present a case successfully treated with fractional CO2 laser showing
      a long-term favourable outcome and no adverse effects. Thus, this modality could
      be an alternative to full ablation for this condition. 

PMID- 25602183
TI  - Molecular characterization and functional expression of the Apis mellifera
      voltage-dependent Ca2+ channels.
AB  - Voltage-gated Ca(2+) channels allow the influx of Ca(2+) ions from the
      extracellular space upon membrane depolarization and thus serve as a transducer
      between membrane potential and cellular events initiated by Ca(2+) transients.
      Most insects are predicted to possess three genes encoding Cavalpha, the main
      subunit of Ca(2+) channels, and several genes encoding the two auxiliary
      subunits, Cavbeta and Cavalpha2delta; however very few of these genes have been
      cloned so far. Here, we cloned three full-length cDNAs encoding the three
      Cavalpha subunits (AmelCav1a, AmelCav2a and AmelCav3a), a cDNA encoding a novel
      variant of the Cavbeta subunit (AmelCavbetac), and three full-length cDNAs
      encoding three Cavalpha2delta subunits (AmelCavalpha2delta1 to 3) of the honeybee
      Apis mellifera. We identified several alternative or mutually exclusive exons in
      the sequence of the AmelCav2 and AmelCav3 genes. Moreover, we detected a stretch
      of glutamine residues in the C-terminus of the AmelCav1 subunit that is
      reminiscent of the motif found in the human Cav2.1 subunit of patients with
      Spinocerebellar Ataxia type 6. All these subunits contain structural domains that
      have been identified as functionally important in their mammalian homologues. For
      the first time, we could express three insect Cavalpha subunits in Xenopus
      oocytes and we show that AmelCav1a, 2a and 3a form Ca(2+) channels with
      distinctive properties. Notably, the co-expression of AmelCav1a or AmelCav2a with
      AmelCavbetac and AmCavalpha2delta1 produces High Voltage-Activated Ca(2+)
      channels. On the other hand, expression of AmelCav3a alone leads to Low Voltage
      Activated Ca(2+) channels. 

PMID- 25602186
TI  - [Fortschritte neurologie - psychiatrie in 2014].

PMID- 25602187
TI  - [Myotonic dystrophies: clinical presentation, pathogenesis, diagnostics and
      therapy].
AB  - The autosomal-dominant myotonic dystrophies dystrophia myotonica type-1 (DM1,
      Curschmann-Steinert disease) and dystrophia myotonica type-2 (DM2, proximal
      myotonic myopathy (PROMM)), are, contrary to the non-dystrophic myotonias,
      progressive multisystem disorders. DM1 and DM2 are the most frequent of the
      muscular dystrophies. In both diseases the skeletal muscle is the most severely
      affected organ (weakness, wasting, myotonia, myalgia). Additionally, they
      manifest in the eye, heart, brain, endocrine glands, gastrointestinal tract,
      skin, skeleton, and peripheral nerves. Phenotypes of DM1 may be classified as
      congenital, juvenile, classical, or late onset. DM2 is a disorder of the middle
      or older age and usually has a milder course compared to DM1. DM1 is due to a CTG
      repeat expansion > 50 repeats in the non-coding 3' UTR of the DMPK-gene. DM2 is
      caused by a CCTG-repeat expansion to 75 - 11 000 repeats in intron-1 of the
      CNBP/ZNF9 gene. Mutant pre-mRNAs of both genes aggregate within the nucleus
      (nuclear foci), which sequester RNA-binding proteins and result in an abnormal
      protein expression via alternative splicing in downstream effector genes (toxic
      RNA diseases). Other mechanisms seem to play an additional pathogenetic role.
      Clinical severity of DM1 increases from generation to generation (anticipation).
      The higher the repeat expansion the more severe the DM1 phenotype. In DM2
      severity of symptoms and age at onset do not correlate with the expansion size.
      Contrary to DM2, there is a congenital form and anticipation in DM1. 

PMID- 25602188
TI  - [Effects of combined cognitive and physical training on cognition of healthy
      older adults: a literature review].
AB  - There is significant evidence for the positive effects of cognitive and physical
      training on cognition in healthy older adults. Recently, it has been discussed
      whether stronger effects could be reached with a combination of both
      interventions. This review analyses the current state of research about this
      topic. Four randomised controlled trials (RCTs) and four controlled trials were
      found. Three of these studies (none of which were RCTs) in fact showed the
      superiority of combined training when compared to single interventions. However,
      even if positive evidence exists, the current state of research has to be
      evaluated as insufficient due to the small number of studies, the lack of
      evidence from RCTs and the lack of comparability of study designs, types of
      interventions, and test intervals used so far. Gaps in the current state of
      research are identified, relevant aspects of future studies are listed and
      possible neurobiological mechanisms of training effects are discussed. 

PMID- 25602189
TI  - [Influence of post-traumatic stress disorder on heart rate variability as marker
      of the autonomic nervous system - a systematic review].
AB  - INTRODUCTION: PTSD is associated with comprehensive disruption of several
      neurobiological regulation mechanisms and with a disruption in the
      parasympathetic-sympathetic balance. This can be measured with the heart rate
      variability (HRV). METHODS: A systematic review in PubMed using the keywords
      "hrv" or "heart rate variability" and "PTSD" or "posttraumatic stress disorder"
      was performed. RESULTS: Overall 15 original studies were identified. In most
      cases a significant relationship of PTSD for reduction of HRV was demonstrated (9
      studies) or, respectively, a reduction by trends was shown in 3 studies.
      Limitations were discussed. DISCUSSION: In spite of the limitations, most of the
      studies have shown a relationship between PTSD and HRV. However, an assessment of
      this potential marker as a supplement for clinical diagnosis and therapy follow
      up in patients with PTSD seems to be premature on the basis of the data obtained
      so far. Further research is required.

PMID- 25602190
TI  - [Characteristics of forensic patients assigned to forensic outpatient treatment].
AB  - OBJECTIVE: In the Federal State of Baden-Wurttemberg an administrative regulation
      specifies which patients should be assigned to forensic outpatient treatment.
      Empirically, little is known about the clinical and criminological factors
      supporting these decisions. METHODS: A complete survey of forensic inpatients in
      Baden-Wurttemberg was undertaken. RESULTS: From 476 patients released from
      unlimited detention (S 63 StGB) 235 (45.6 %) received a court order for forensic
      aftercare between 2009 and 2012. Social, forensic, and psychiatric history
      differed only slightly compared with patients not assigned. Schizophrenia as
      diagnosis was overrepresented, personality disorder and paraphilia
      underrepresented. Both groups differed most with respect to the duration of
      detention. CONCLUSIONS: The decision for forensic outpatient treatment seems to
      be determined by process variables of inpatient treatment but not by
      criminological risk factors. This contradicts the R-N-R principles by Andrews and
      Bonta.

PMID- 25602191
TI  - [Akinetic mutism due to fulminant multilocular cerebral venous thrombosis,
      including the vein of Galen].
AB  - Cerebral venous thrombosis may present with multifaceted symptoms and therefore
      be difficult to diagnose. Only few evidence-based data exist with respect to
      therapy and prognosis, especially concerning the deep cerebral venous system. A
      thrombosis of the vein of Galen is deemed to have a poorer prognosis. Our case
      report describes the local combined neuro-interventional therapy as an individual
      attempt to cure a patient with a fulminant disease course. 

PMID- 25602192
TI  - [Depressive disorders in juveniles: diagnosis and therapy].

PMID- 25602193
TI  - Modular synthesis of metal-organic complex arrays containing precisely designed
      metal sequences.
AB  - A modular synthetic approach is reported for the synthesis of heterometallic
      metal-organic complex arrays (MOCAs). Modules of four metal centers containing
      three different metals copper(II), nickel(II), platinum(II), or ruthenium(II) are
      prepared using a solid-phase polypeptide synthesis technique and then linked in
      solution to make MOCAs of eight metal centers as linear, T-branched, and H
      branched compounds. The MOCA molecular topologies thus have specific unique
      linear and branched sequences of metals along the peptide backbone. 

PMID- 25602194
TI  - Prediction of Henry's Law Constants via group-specific quantitative structure
      property relationships.
AB  - Henry's Law Constants (HLCs) for several hundred organic compounds in water at 25
      degrees C were predicted by Quantitative Structure Property Relationship (QSPR)
      models, with the division of organic compounds into specific classes to yield
      more accurate models than generalised ones. Both multiple linear regression (MLR)
      and artificial neural network (ANN) versions of models were produced for three
      general cases, encompassing the entire data set; one used the six best
      descriptors, as determined by maximising the correlation coefficient; another
      used the twelve best descriptors in a similar manner, whilst the third used the
      same twelve descriptors as English and Carroll (2001). These achieved,
      respectively, root-mean square errors (RMSEs) of 0.719, 0.52 and 0.607 log(Hcc)
      units for the MLR version and 0.601, 0.394 and 0.431 for the test set of the ANN
      models, where Hcc is the ratio of the compound's concentration in the vapour
      phase to that in the liquid phase. These were compared with models for six
      specific chemical classes: (i) alkanes, (ii) cyclic alkanes, (iii) alkenes, (iv)
      halogenated compounds, (v) aldehydes, ketones and esters grouped together, and
      (vi) monoaromatics. These group-specific models had RMSEs of 0.153, 0.141. 0.097,
      0.168, 0.122 and 0.104 respectively for the MLR versions and 0.684, 0.719, 0.856,
      0.784, 0.875 and 0.861 for the test set of the ANN models. It was found that the
      class-specific models achieved lower RMSEs than the general models, when using
      MLR models. The use of ANN was found to improve the predictive accuracy of the
      general models but failed to improve that for the class-specific models vis-a-vis
      MLR.

PMID- 25602195
TI  - Protocolized sedation in critically ill children.

PMID- 25602196
TI  - Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey.
AB  - BACKGROUND: Atherosclerosis is one of the main risk factors cause acute cerebral
      cardio vascular diseases. It's of great significance to establish an
      atherosclerosis animal model that can mimic the characteristics and nature course
      of human patients. Therefore, a rhesus monkey model was induced by high-fat diet
      to monitor their lipid profile and intima-media thickness (IMT) of artery walls
      and study atherosclerosis progression. METHODS: Fifty male rhesus monkeys were
      enrolled in this study. All of these monkeys were aged 7 to 14 years with BMI >30
      kg/m2. They were fed with high-fat diet containing 10% of fat for the first 48
      weeks. Use ultrasound to measure the IMT at bilateral common carotid arteries and
      their bifurcations and aorta (AO) of the monkeys, and screen out the individuals
      with thickened IMT for the next phase. In the next 48 weeks, some of these
      monkeys (n = 4) were fed with standard diet containing 3% fat. Meanwhile the
      other monkeys (n = 5) were fed with high-fat diet for another 48 weeks. Their
      serum lipid level was monitored and arterial IMT was also determined
      periodically. RESULTS: Serum lipid level of all 50 monkeys elevated after fed
      with high-fat diet for the first 48 weeks. IMT thickening at right common carotid
      bifurcation and aorta (AO) was thickened in 9 monkeys. Furthermore, 4 of these 9
      monkeys were fed with standard diet and other 5 monkeys were fed with high-fat
      diet in the following 48 weeks. The serum lipid level of the 4 monkeys recovered
      and their IMT at RBIF and AO did not progress. However, the lipid level of other
      5 monkeys remained high, and their IMT thickening of AO progressed, and plaques
      and calcification focuses were found at the anterior wall of aorta near the
      bifurcation of common iliac artery. CONCLUSIONS: After high-fat diet induction
      for 96 weeks, serum lipid levels of rhesus monkeys elevated significantly, which
      subsequently caused IMT thickening and plaques formation. When IMT thickening
      occurred, further vascular injury may be prevented by reducing diet fat content.
      Our study indicates that vascular injury of high-fat diet induced rhesus monkey
      is similar to that of human in position and progression.

PMID- 25602197
TI  - Does previous corticosteroid treatment affect the inflammatory infiltrate found
      in polymyositis muscle biopsies?
AB  - OBJECTIVES: The aim of the study was to evaluate the effect of the prior use of
      corticosteroids (CS) on the presence of inflammatory infiltrates (InI) in muscle
      biopsies of polymyositis (PM). METHODS: We retrospectively evaluated 60 muscle
      biopsy samples that had been obtained at the time of the diagnosis of PM. The
      patients were divided into three groups according to the degree of the InI
      present in the muscle biopsies: (a) minimal InI present only in an interstitial
      area of the muscle biopsy (endomysium, perimysium) or in a perivascular area; (B)
      moderate InI in one or two areas of the interstitium or of the perivascular area;
      and (C) moderate InI throughout the interstitium or intense inflammation in at
      least one area of the interstitium or of the perivascular area. RESULTS: The
      three groups were comparable regarding the demographic, clinical and laboratory
      features (p>0.05). Approximately half of the patients in each group were using CS
      at the time of the muscle biopsy. The median (interquartile) duration of CS use
      [4 (0-38), 4 (0-60) and 5 (0-60) days: groups A, B and C, respectively] and the
      median cumulative CS dose used [70 (0-1200), 300 (0-1470) and 300 (0-1800)mg]
      were similar between the groups (p>0.05). CONCLUSIONS: Previous CS use did not
      influence the presence or the degree of InI found in muscle biopsies in PM with
      clinical and laboratory disease activity. Our study showed that muscle biopsies
      should be performed this population, even in individuals who have already been
      taking CSs.

PMID- 25602198
TI  - Internet-Based Partner Services in US Sexually Transmitted Disease Prevention
      Programs: 2009-2013.
AB  - BACKGROUND: Social networking sites have become increasingly popular venues for
      meeting sex partners. Today, some sexually transmitted disease (STD) programs
      conduct Internet-based partner services (IPS). The purpose of the study was to
      explore how the Internet is being used by STD prevention programs to perform
      partner services. METHODS: We assessed US STD prevention programs receiving funds
      through the 2008-2013 Comprehensive STD Prevention Systems cooperative agreement.
      We (1) reviewed 2009 IPS protocols in 57 funding applications against a benchmark
      of national guidelines and (2) surveyed persons who conducted IPS in
      jurisdictions conducting IPS in 2012. RESULTS: Of the 57 project areas receiving
      Comprehensive STD Prevention Systems funds, 74% provided an IPS protocol. States
      with IPS protocols had larger populations and more gonorrhea and syphilis cases
      (t = 2.2-2.6; all Ps < .05), although not higher rates of infection. Most
      protocols included staffing (92%) and IPS documentation (87%) requirements, but
      fewer had evaluation plans (29%) or social networking site engagement strategies
      (16%). Authority to perform a complete range of IPS activities (send e-mail, use
      social networking sites) was associated with contacting more partners via IPSs (P
      < .05). CONCLUSIONS: This study provides a snapshot of IPS activities in STD
      programs in the United States. Further research is needed to move from assessment
      to generating data that can assist training efforts and program action and,
      finally, to enable efficient IPS programs that are integrated into STD prevention
      and control efforts.

PMID- 25602199
TI  - Nitrous Oxide Fluxes in Fertilized L. Plantations across a Gradient of Soil
      Drainage Classes.
AB  - The effect of fertilizer management on nitrous oxide (NO) fluxes in agricultural
      ecosystems is well documented; however, our knowledge of these effects in managed
      forests is minimal. We established a comprehensive research study to address this
      knowledge gap across a range of soil drainage classes (poorly, moderately, and
      well drained) common in southern pine plantation management. Fertilizer
      treatments in each drainage class comprised of control (no fertilizer), urea +
      phosphorus (P), and P-coated urea fertilizer (CUF). Fertilization (168 kg N ha)
      occurred independently during the spring, summer, and fall to assess the effects
      of application timing. Nitrous oxide sampling, using vented static chambers,
      started immediately after seasonal fertilizer application and was performed every
      6 wk for more than 1 yr. Time-integrated net annual NO emissions increased with
      urea (1.15 kg NO-N ha) and CUF (0.88 kg NO-N ha) application compared with
      unfertilized control (0.22 kg NO-N ha). Mean annual NO flux was significantly
      increased with fall fertilization (1.17 kg NO-N ha) relative to spring (0.73 kg
      NO-N ha) or summer (0.33 kg NO-N ha). Similarly, average annual NO flux was
      higher in poorly drained soils (1.40 kg NO-N ha) than in moderately drained (0.46
      kg NO-N ha) and well-drained soils (0.39 kg NO-N ha). This study suggests that NO
      emissions after fertilization can be minimized by avoiding fall fertilization and
      poorly drained soils and by selecting enhanced-efficiency N fertilizers over
      urea. 

PMID- 25602200
TI  - Seasonal nitrous oxide and methane fluxes from grain- and forage-based production
      systems in wisconsin, USA.
AB  - Agriculture in the midwestern United States is a major anthropogenic source of
      nitrous oxide (NO) and is both a source and sink for methane (CH), but the degree
      to which cropping systems differ in emissions of these gases is not well
      understood. Our objectives were to determine if fluxes of NO and CH varied among
      cropping systems and among crop phases within a cropping system. We compare NO
      and CH fluxes over the 2010 and 2011 growing seasons from the six cropping
      systems at the Wisconsin Integrated Cropping Systems Trial (WICST), a 20-yr-old
      cropping systems experiment. The study is composed of three grain and three
      forage cropping systems spanning a spectrum of crop diversity and perenniality
      that model a wide range of realistic cropping systems that differ in management,
      crop rotation, and fertilizer regimes. Among the grain systems, cumulative
      growing season NO emissions were greater for continuous corn ( L.) (3.7 kg NO-N
      ha) than corn-soybean [ (L.) Merr.] (2.0 kg NO-N ha) or organic corn-soybean
      wheat ( L.) (1.7 kg NO-N ha). Among the forage systems, cumulative growing-season
      NO emissions were greater for organic corn-alfalfa ( L.)-alfalfa (2.9 kg NO-N ha)
      and conventional corn-alfalfa-alfalfa-alfalfa (2.5 kg NO-N ha), and lower for
      rotational pasture (1.9 kg NO-N ha). Application of mineral or organic N
      fertilizer was associated with elevated NO emissions. Yield-scaled emissions (kg
      NO-N Mg) did not differ by cropping system. Methane fluxes were highly variable
      and no effect of cropping system was observed. These results suggest that
      extended and diversified cropping systems could reduce area-scaled NO emissions
      from agriculture, but none of the systems studied significantly reduced yield
      scaled NO emissions. 

PMID- 25602201
TI  - Resurgent beaver ponds in the northeastern United States: implications for
      greenhouse gas emissions.
AB  - Beaver ponds, a wetland type of increasing density in the northeastern United
      States, vary spatially and temporally, creating high uncertainty in their impact
      to greenhouse gas (GHG) emissions. We used floating static gas chambers to assess
      diffusive fluxes of methane (CH), carbon dioxide (CO), and nitrous oxide (NO)
      from the air-water interface of three beaver ponds (0.05-8 ha) in Rhode Island
      from fall 2012 to summer 2013. Gas flux was based on linear changes of gas
      concentrations in chambers over 1 h. Our results show that these beaver ponds
      generated considerable CH and CO emissions. Methane flux (18-556 mg m d) showed
      no significant seasonal differences, but the shallowest pond generated
      significantly higher CH flux than the other ponds. Carbon dioxide flux (0.5-22.0
      g m d) was not significantly different between sites, but it was significantly
      higher in the fall, possibly due to the degradation of fresh leaves. Nitrous
      oxide flux was low (0-2.4 mg m d). Overall, CH and CO comprised most of the
      global warming potential, 61 and 38%, respectively. The shallowness of the beaver
      ponds may have limited the time needed for CH oxidation to CO before CH escaped
      to the atmosphere. Beaver dams also increase the aerial extent of hydric soils,
      which may transform riparian areas from upland GHG sinks to wetland GHG sources
      thereby changing the net global warming potential. Further studies tracking the
      pattern and conditions of beaver pond creation and abandonment will be essential
      to understanding their role as GHG sources. 

PMID- 25602202
TI  - Spatial and seasonal variations of the air pollution index and a driving factors
      analysis in china.
AB  - In this study, the daily air pollution index (API) of 110 cities based on ground
      monitoring was conducted on the 2011 data set from the Ministry of Environmental
      Protection of China. The pollutant concentrations, seasonal variations, and
      spatial autocorrelations were evaluated. The results show that the major
      principal pollutants in China are inhalable particles. In addition, the total
      number of clean days (API <= 50) is apparently smaller in the northern cities
      than in the southern cities as a result of fuel utilization and large-scale
      organized central heating. Seasonally, air pollution is most severe in winter and
      is caused by low-frequency rainfall, strong northwest winds, dry climate, and
      high energy consumption; this is followed by spring, which is a season of
      frequent sandstorms. According to spatial autocorrelation analysis, clusters with
      high API value agglomeration (High-High clusters) are mainly concentrated in the
      middle and northern parts of China, whereas clusters with low API agglomeration
      (Low-Low clusters) are principally concentrated in the southern parts of China
      due to a favorable climate and abundant rainfall. Meteorological data, including
      wind speed and temperature, have great impacts on API. The air quality effects of
      industrial structure, energy use, urban greening, and traffic congestion were
      also analyzed. With the ecological function of purifying the air, industries that
      use natural resources and urban greening could help to reduce API, whereas
      secondary industry and gas use, which have a positive coefficient, increase the
      API value. The risk of exposure to poor air quality is largest in the winter,
      smallest in the summer, and remains relatively unchanged in the spring and
      autumn. 

PMID- 25602203
TI  - Ammonia volatilization after surface application of laying-hen and broiler
      chicken manures.
AB  - Ammonia (NH) losses after field application of animal manure are affected by
      manure characteristics. The objectives of this study were to quantify NH losses
      from poultry manures obtained from varied handling and storage systems commonly
      found in eastern Canada and to relate NH emissions to manure characteristics. We
      measured NH volatilization using wind tunnels for 22 d after soil-surface
      application of seven solid poultry manures originating from farms varying in
      production type (laying hens and broiler chickens) and in storage duration and
      conditions. Cumulative emissions (2.7-7.0 g NH-N m) accounted for 13.6 to 35.0%
      of the total N applied and 51 to 84% (mean, 70%) of the sum of ammoniacal N, urea
      N, and uric acid N applied (TAUA). On average, 20% of these losses occurred
      during the first 4.5 h after application for manures that were not dried in the
      barn shortly after excretion. Production type and storage durations could not
      explain differences in NH volatilization between manures. Volatilization losses
      were linearly related to manure dry matter and to manure-derived NH-N, but
      sources of N changed with time after application. During the first 7 d,
      variations in total ammoniacal N applied (TANA) among manures explained most of
      the variations in cumulative NH losses ( = 0.85 after 26 h and 0.92 after 7 d).
      After a simulated rainfall (5 mm) on Day 7 that stimulated the decomposition of
      uric acid in manures, TAUA rather than TANA was related to cumulative emissions (
      = 0.77 after 14 and 22 d). Our results indicate that reliable estimates of NH
      volatilization after land spreading of poultry manures should be based not only
      on TANA but also on NH-N derived from the decomposition of uric acid, that
      volatilization losses reported in the literature (including the present study)
      averaged 50% of TAUA, and that estimates for a given situation also need to
      account for local environmental conditions. 

PMID- 25602204
TI  - Meteorological influences on nitrogen dynamics of a coastal onsite wastewater
      treatment system.
AB  - On-site wastewater treatment systems (OWTS) can contribute nitrogen (N) to
      coastal waters. In coastal areas with shallow groundwater, OWTS are likely
      affected by meteorological events. However, the meteorological influences on
      temporal variability of N exports from OWTS are not well documented.
      Hydrogeological characterization and seasonal monitoring of wastewater and
      groundwater quality were conducted at a residence adjacent to the Pamlico River
      Estuary, North Carolina, during a 2-yr field study (October 2009-2011). Rainfall
      was elevated during the first study year, relative to the annual mean. In the
      second year, drought was followed by extreme precipitation from Hurricane Irene.
      Recent meteorological conditions influenced N speciation and concentrations in
      groundwater. Groundwater total dissolved nitrogen (TDN) beneath the OWTS
      drainfield was dominated by nitrate during the drought; during wetter periods,
      ammonium and organic N were common. Effective precipitation (precipitation [P]
      minus evapotranspiration [ET]) affected OWTS TDN exports because of its influence
      on groundwater recharge and discharge. Groundwater nitrate-N concentrations
      beneath the drainfield were typically higher than 10 mg/L when total biweekly
      precipitation was less than evapotranspiration (precipitation deficit: P < ET).
      Overall, groundwater TDN concentrations were elevated above background
      concentrations at distances >15 m downgradient of the drainfield. Although OWTS
      nitrate inputs caused elevated groundwater nitrate concentrations between the
      drainfield and the estuary, the majority of nitrate was attenuated via
      denitrification between the OWTS and 48 m to the estuary. However, DON
      originating from the OWTS was mobile and contributed to elevated TDN
      concentrations along the groundwater flowpath to the estuary. 

PMID- 25602205
TI  - Biochar Reduces Zinc and Cadmium but not Copper and Lead Leaching on a Former
      Sewage Field.
AB  - The leaching of trace metals from anthropogenically contaminated sites poses the
      risk of groundwater pollution. Biochar has recently been proposed as a soil
      additive to reduce trace-metal concentrations in the soil solution and to
      increase water retention, thus reducing drainage. However, field studies on the
      effects of biochar addition on trace-metal leaching are scarce. Therefore, we
      added 0, 1, 2.5, and 5 g 100 g of biochar derived from giant miscanthus ( * J.M.
      Greef & Deuter ex Hodk. & Renvoize) to soil contaminated by former wastewater
      irrigation and examined water retention and cumulative leaching of Zn, Cd, Cu,
      and Pb in a 2-yr field study. Cumulative trace-metal leaching was determined by
      self-integrating accumulators (SIAs) based on ion-exchange resins and compared
      with data calculated from mean concentrations in the soil solution collected with
      tension lysimeter plates and groundwater recharge rate. The highest rate of
      biochar addition increased water retention and thus reduced the amount of
      drainage water. Mean cumulative Zn and Cd fluxes decreased due to both reduced
      concentrations in the soil solution and reduced drainage. Although Cu and Pb
      concentrations in the soil solution increased with biochar addition, the reduced
      drainage resulted in similar fluxes in the biochar and the control treatment. The
      cumulative Zn, Cd, and Cu fluxes determined with SIAs were in the same range as
      the calculated values, while SIA-based Pb fluxes were much higher than those
      calculated. Since the suction plates excluded colloids, the high SIA-based Pb
      fluxes indicate colloidal transport and reveal the importance to elucidate the
      colloidal pathway for risk assessment. 

PMID- 25602206
TI  - Biochar amendment affects leaching potential of copper and nutrient release
      behavior in contaminated sandy soils.
AB  - Copper (Cu) contamination to soil and water is a worldwide concern. Biochar has
      been suggested to remediate degraded soils. In this study, column leaching and
      chemical characterization were conducted to assess effects of biochar amendment
      on Cu immobilization and subsequent nutrient release in Cu-contaminated Alfisol
      and Spodosol. The results indicate that biochar is effective in binding Cu (30
      and 41%, respectively, for Alfisol with and without spiked Cu; 36 and 43% for
      Spodosol) and reducing Cu leaching loss (from ~47 to 10% for the Cu-spiked
      Alfisol and from 48 to 9% for the Cu-spiked Spodosol). Copper was likely retained
      on biochar surfaces through complexation, as suggested by Fourier-transform
      infrared spectra. Biochar amendment converts a portion of Cu from available pool
      to more stable forms, thus resulting in decreased activities of free Cu and
      increased activity of organic Cu complexes in leachate. Reduction of >0.45-MUm
      solids and nanoparticles concentrations in leachate was also observed. In
      addition, biochar application rate was correlated negatively with P, Ca, Mg, Zn,
      Mn, and NH-N concentration ( < 0.05) but positively with K and Na concentration (
      < 0.05) in leachates. These results documented the potential of biochar as an
      effective amendment for Cu immobilization and mitigation of leaching risk for
      some nutrients. 

PMID- 25602207
TI  - Effects of agricultural conservation practices on N loads in the Mississippi
      atchafalaya river basin.
AB  - A modeling framework consisting of a farm-scale model, Agricultural Policy
      Environmental Extender (APEX); a watershed-scale model, Soil and Water Assessment
      Tool (SWAT); and databases was used in the Conservation Effects Assessment
      Project to quantify the environmental benefits of conservation practices on
      cropland. APEX is used to simulate conservation practices on cultivated cropland
      and Conservation Reserve Program land to assess the edge-of-field water-quality
      benefits. Flow and pollutant loadings from APEX are input to SWAT. SWAT simulates
      the remaining noncultivated land and routes flow and loads generated from
      noncultivated land, point sources, and cropland to the basin outlet. SWAT is used
      for assessing the effects of practices on local and in-stream water-quality
      benefits. Each river basin is calibrated and validated for streamflow and loads
      at multiple gauging stations. The objectives of the current study are to estimate
      the effects of currently existing and additional conservation practices on total
      N (TN) loads in the Mississippi-Atchafalaya River Basin (MARB) and draw insights
      on TN load reductions necessary for reducing the hypoxic zone in the Gulf of
      Mexico. The effects of conservation practice scenarios on local and in-stream
      (riverine) water quality are evaluated. Model results indicate that conservation
      practices currently on cropland have reduced the TN losses to local waters
      between 20 and 59% in the six river basins within MARB and the TN load discharged
      to the Gulf by 17%. Further water-quality improvement can be obtained in the MARB
      with additional conservation treatment. 

PMID- 25602208
TI  - The use of phytometers for evaluating restoration effects on riparian soil
      fertility.
AB  - The ecological restoration of streams in Sweden has become increasingly important
      to counteract effects of past timber floating. In this study, we focused on the
      effect on riparian soil properties after returning coarse sediment (cobbles and
      boulders) to the channel and reconnecting riparian with in-stream habitats.
      Restoration increases habitat availability for riparian plants, but its effects
      on soil quality are unknown. We also analyzed whether the restoration effect
      differs with variation in climate and stream size. We used standardized plant
      species to measure the performance of a grass ( L.) and a forb ( L.) in soils
      sampled in the riparian zones of channelized and restored streams and rivers.
      Furthermore, we analyzed the mass fractions of carbon (C) and nitrogen (N) along
      with the proportions of the stable isotopes C and N in the soil, as well as its
      grain size composition. We found a positive effect of restoration on biomass of
      phytometers grown in riparian soils from small streams, indicating that
      restoration enhanced the soil properties favoring plant performance. We suggest
      that changed flooding with more frequent but less severe floods and slower flows,
      enhancing retention, could explain the observed patterns. This positive effect
      suggests that it may be advantageous to initiate restoration efforts in small
      streams, which make up the highest proportion of the stream network in a
      catchment. Restoration responses in headwater streams may then be transmitted
      downstream to facilitate recovery of restored larger rivers. If the larger rivers
      were restored first, a slower reaction would be expected. 

PMID- 25602209
TI  - Release of Pharmaceuticals under Reducing Conditions in a Wastewater-Irrigated
      Mexican Soil.
AB  - Wastewater irrigation is often performed by flood irrigation, leading to changes
      in redox potential (Eh) of irrigated soils. In addition to soil organic matter,
      Fe-(hydr)oxides are important sorbents for pollutants, and biotransformation of
      pollutants can be accelerated under reducing conditions. Here, the influence of
      reducing conditions on the release of sorbed pharmaceuticals from soil and their
      potential accelerated dissipation was investigated in a microcosm study. Samples
      of a soil from the Mezquital Valley (Mexico) irrigated for 85 yr with untreated
      wastewater were incubated under oxidizing (Eh of 500 +/- 20 mV), weakly reducing
      (Eh of 100 +/- 20 mV), and moderately reducing (Eh of -100 +/- 20 mV) soil
      conditions for 30 to 31 d. The concentrations of nine pharmaceuticals
      (bezafibrate, carbamazepine, ciprofloxacin, sulfamethoxazole, trimethoprim,
      enrofloxacin, clarithromycin, diclofenac, and naproxen) were extracted via solid
      phase extraction from soil slurries and analyzed by liquid chromatography-tandem
      mass spectrometry. Low Eh did not lead to a release of formerly sorbed
      pharmaceuticals from the wastewater irrigated soil. High pH values (>8) of the
      examined soil resulting from denitrification under reducing conditions prevented
      the dissolution of Fe-(hydr)oxides and, hence, the potential release of
      pharmaceuticals. A trend of decreasing concentrations of sulfamethoxazole and
      bezafibrate with time under moderately reducing conditions supports previous
      findings of a transformation of these compounds under anaerobic conditions. 

PMID- 25602210
TI  - Vadose Zone Transport of Natural and Synthetic Estrogen Hormones at Penn State's
      "Living Filter" Wastewater Irrigation Site.
AB  - The increase in endocrine-disrupting compounds in the environment has generated
      research focused on the behavior of these compounds in natural soil and water
      ecosystems. To understand how estrogens behave in the soil environment as a
      result of 25+ yr of wastewater irrigation, soils from Penn State's "Living
      Filter" wastewater irrigation site were extracted and analyzed for two natural
      estrogens (17beta-estradiol and estrone) and one synthetic estrogen (17alpha
      ethynylestradiol). Soil estrogen concentrations were compared for two independent
      variables: type of land cover and sampling time. Soils were sampled from cropped
      and forested land areas, and soils were sampled 2 d and 3 wk after a single 12-h
      effluent irrigation event. A nonirrigated control site was sampled to provide
      natural background data. For 17beta-estradiol, the nonirrigated mean
      concentration was 0.68 +/- 0.11 ng cm, and the irrigated values, including
      samples from both land areas and time frames, ranged from 0.99 +/- 0.11 to 1.82
      +/- 0.69 ng cm. For estrone, the nonirrigated mean concentration was 2.36 +/-
      0.22 ng cm, and the irrigated values, including samples from both land areas
      collected and time frames, ranged from 2.18 +/- 0.20 to 6.24 +/- 3.14 ng cm. The
      17alpha-ethynylestradiol nonirrigated mean concentration was 0.47 +/- 0.40 ng cm.
      The irrigated values, including samples from both land areas and time frames,
      ranged from 0.25 +/- 0.06 to 1.37 +/- 0.39 ng cm. This study found that time of
      sampling, land cover, and irrigation can affect estrogen concentrations in soils,
      resulting in levels that exceed natural background and require improvements in
      management practices. 

PMID- 25602211
TI  - Distribution and source apportionment of polycyclic aromatic hydrocarbons in
      soils and leaves from high-altitude mountains in southwestern china.
AB  - Several studies have investigated the distribution patterns and geographic
      sources of polycyclic aromatic hydrocarbons (PAHs) in mountainous areas. Little
      is known about how different sources contribute to PAH concentrations at
      different elevations along mountain slopes. To estimate the distribution and
      sources of PAHs at different altitudes in mountainous areas of southwestern
      China, samples of soils and leaves from trees were collected from 1000 to 1500 m
      asl in the Dawangling forest and analyzed for PAHs. Total PAH concentrations
      ranged from 93.9 to 802.3 ng g (average, 252.3 ng g) in soils and from 4.1 to
      100.9 ng g (average, 23.1 ng g) in leaves. Our results suggest that soil PAH
      levels in the study area could be classified as "weakly contaminated." The PAH
      levels in leaves from the Dawangling forest were lower than those found in
      Himalayan spruce needles from the central Himalayas in China and from an
      agricultural station in southern England. Total PAHs in the Dawangling forest
      soils increased with elevation, primarily due to the low-molecular-weight PAHs,
      which accumulated in samples from higher altitudes. In contrast, high-molecular
      weight PAHs were inversely related to or unrelated to elevation. The PAH profiles
      were similar in soils and leaves from all mountainous regions. Diagnostic ratios
      showed that the PAHs in soils at different altitudes were from different
      pollution emission sources; therefore, PAHs in the entire study area were
      probably derived from mixed sources. Cluster analyses confirmed that liquefied
      petroleum gas, coal/wood combustion, and petroleum combustion were likely the
      predominant PAH sources in this region. 

PMID- 25602212
TI  - Effects of heavy metals on the sorption of polycyclic aromatic hydrocarbons by.
AB  - To date, little is known about the effects of heavy metals on the sorption of
      organic contaminants by phytoplankton. In this study, the effects of Cu, Cd, and
      Ag on the sorption of polycyclic aromatic hydrocarbons (PAHs) by were studied.
      Phenanthrene sorption was facilitated by low concentrations of metal salts (<=20
      MUmol L) and was significantly suppressed in the presence of 50 to 200 MUmol L
      metal salts and rebounded and exceeded the control in the presence of 500 to 5000
      MUmol L Cu(NO) and AgNO, respectively. Although the ionic strengths of the
      solutions were the same, phenanthrene sorption was different in the presence of
      the same concentrations of Cu(NO) and Cd(NO) especially in the high concentration
      range. In the high concentration range, Ag was much more effective than Cu and Cd
      to increase phenanthrene sorption. In contrast to phenanthrene, sorption of both
      pyrene and benzo[a]pyrene increased dramatically in the presence of Cu(NO). The
      cation-pi interactions between the metal cations and PAHs facilitated the
      sorption of the PAHs. Sorption enhancement of the PAHs caused by the cation-pi
      interactions increased with the softness order of the metals (Cd < Cu < Ag) and
      the pi donor strength order of the PAHs (phenanthrene < pyrene < benzo[a]pyrene).
      This study suggests that sorption of PAHs by cyanobacteria can be significantly
      altered by concentrations and properties of both heavy metals and PAHs. 

PMID- 25602213
TI  - Grazing and no-till cropping impacts on nitrogen retention in dryland
      agroecosystems.
AB  - As the world's population increases, marginal lands such as drylands are likely
      to become more important for food production. One proven strategy for improving
      crop production in drylands involves shifting from conventional tillage to no
      till to increase water use efficiency, especially when this shift is coupled with
      more intensive crop rotations. Practices such as no-till that reduce soil
      disturbance and increase crop residues may promote C and N storage in soil
      organic matter, thus promoting N retention and reducing N losses. By sampling
      soils 15 yr after a N tracer addition, this study compared long-term soil N
      retention across several agricultural management strategies in current and
      converted shortgrass steppe ecosystems: grazed and ungrazed native grassland,
      occasionally mowed planted perennial grassland, and three cropping intensities of
      no-till dryland cropping. We also examined effects of the environmental variables
      site location and topography on N retention. Overall, the long-term soil N
      retention of >18% in these managed semiarid ecosystems was high compared with
      published values for other cropped or grassland ecosystems. Cropping practices
      strongly influenced long-term N retention, with planted perennial grass systems
      retaining >90% of N in soil compared with 30% for croplands. Grazing management,
      topography, and site location had smaller effects on long-term N retention.
      Estimated 15-yr N losses were low for intact and cropped systems. This work
      suggests that semiarid perennial grass ecosystems are highly N retentive and that
      increased intensity of semiarid land management can increase the amount of
      protein harvested without increasing N losses. 

PMID- 25602214
TI  - Granular and Dissolved Polyacrylamide Effects on Erosion and Runoff under
      Simulated Rainfall.
AB  - Polyacrylamide (PAM) has been demonstrated to reduce erosion under many
      conditions, but less is known about the effects of its application method on
      erosion and concentrations in the runoff water. A rainfall simulation study was
      conducted to evaluate the performance of an excelsior erosion control blanket
      (cover) and two PAM application methods. The treatments were (i) no cover + no
      PAM (control), (ii) cover + no PAM, (iii) cover + granular PAM (GPAM), and (iv)
      cover + dissolved PAM (DPAM) applied to soil packed in wooden runoff boxes. The
      GPAM or DPAM (500 mg L) was surface-applied at a rate of 30 kg ha 1 d before
      rainfall simulation. Rainfall was applied at 83 mm h for 50 min and then repeated
      for another 20 min after a 30-min rest period. Runoff samples were analyzed for
      volume, turbidity in nephelometric turbidity units (NTU), total suspended solids
      (TSS), sediment particle size distribution, and PAM concentration. The cover
      alone reduced turbidity and TSS in runoff by >60% compared with the control (2315
      NTU, 2777 mg TSS L). The PAM further reduced turbidity and TSS by >30% regardless
      of the application method. The median particle diameter of eroded sediments for
      PAM treatments was seven to nine times that of the control (12.4 MUm). Loss of
      applied PAM in the runoff water (not sediment) was 19% for the GPAM treatment but
      only 2% for the DPAM treatment. Both GPAM and DPAM were effective at improving
      groundcover performance, but DPAM resulted in much less PAM loss. 

PMID- 25602215
TI  - Low transient storage and uptake efficiencies in seven agricultural streams:
      implications for nutrient demand.
AB  - We used mass load budgets, transient storage modeling, and nutrient spiraling
      metrics to characterize nitrate (NO), ammonium (NH), and inorganic phosphorus
      (SRP) demand in seven agricultural streams across the United States and to
      identify in-stream services that may control these conditions. Retention of one
      or all nutrients was observed in all but one stream, but demand for all nutrients
      was low relative to the mass in transport. Transient storage metrics (/, , , and
      ) correlated with NO retention but not NH or SRP retention, suggesting in-stream
      services associated with transient storage and stream water residence time could
      influence reach-scale NO demand. However, because the fraction of median reach
      scale travel time due to transient storage () was <=1.2% across the sites, only a
      relatively small demand for NO could be generated by transient storage. In
      contrast, net uptake of nutrients from the water column calculated from nutrient
      spiraling metrics were not significant at any site because uptake lengths
      calculated from background nutrient concentrations were statistically
      insignificant and therefore much longer than the study reaches. These results
      suggest that low transient storage coupled with high surface water NO inputs have
      resulted in uptake efficiencies that are not sufficient to offset groundwater
      inputs of N. Nutrient retention has been linked to physical and hydrogeologic
      elements that drive flow through transient storage areas where residence time and
      biotic contact are maximized; however, our findings indicate that similar
      mechanisms are unable to generate a significant nutrient demand in these streams
      relative to the loads. 

PMID- 25602216
TI  - River bank materials as a source and as carriers of phosphorus to lake pepin.
AB  - Lake Pepin, a natural impoundment on the Upper Mississippi River, has water
      quality problems of high sedimentation rates and elevated phosphorus (P) levels.
      The majority of sediments in Lake Pepin come from river banks consisting of fine
      tills in the Minnesota River Basin. Since 1850, inorganic P concentrations in
      lake sediments have continuously increased. This study explored whether the
      increase in inorganic P concentrations can be explained through selective
      transport of fine particles combined with in-stream P adsorption. The
      measurements included total P (TP) content, P adsorption/desorption isotherms,
      and the solution equilibrium P concentration at zero adsorption (EPC) for various
      bank materials. Results showed that till bank materials are inherently high in TP
      (>400 mg kg), have strong P binding ability, and have low EPC (<0.1 mg L).
      Selective transport of fine particles from bank materials explained the inorganic
      P concentrations of Lake Pepin sediments before 1850. After 1850, P adsorption
      from the water column simulating historic river pollution and additional
      selective transport of fine particles further explained the increasing inorganic
      P concentrations in lake sediments. We conclude that the increasing P
      concentrations in Lake Pepin sediments are largely the sewage and industrial
      waste P that was picked up by fine particles of bank materials from river waters.
      Because a substantial reduction in sediment load from bank materials may be
      difficult to achieve, we suggest directing efforts toward insuring that P
      additions to rivers upstream of Lake Pepin do not result in P concentration
      greater than the EPC value of bank materials. 

PMID- 25602217
TI  - Adhesion of and to soil in runoff as influenced by polyacrylamide.
AB  - Polyacrylamide (PAM) is used in agriculture to reduce soil erosion and has been
      reported to reduce turbidity, nutrients, and pollutants in surface runoff water.
      The objective of this work was to determine the effect of PAM on the
      concentration of enteric bacteria in surface runoff by comparing four enteric
      bacteria representing phenotypically different motility and hydrophobicity from
      three soils. Results demonstrated that bacterial surface runoff was
      differentially influenced by the PAM treatment. Polyacrylamide treatment
      increased surface runoff for adhered and planktonic cells from a clay soil;
      significantly decreased surface runoff of adhered bacteria, while no difference
      was observed for planktonic bacteria from the sandy loam; and significantly
      decreased the surface runoff of planktonic cells, while no difference was
      observed for adhered bacteria from the clay loam. Comparing strains from a final
      water sample collected after 48 h showed a greater loss of while serovar Poona
      was almost not detected. Thus, (i) the PAM efficiency in reducing the
      concentration of enteric bacteria in surface runoff was influenced by soil type
      and (ii) variation in the loss of enteric bacteria highlights the importance of
      strain-specific properties that may not be captured with general fecal indicator
      bacteria. 

PMID- 25602218
TI  - Intensive management in grasslands causes diffuse water pollution at the farm
      scale.
AB  - Arable land use is generally assumed to be the largest contributor to
      agricultural diffuse pollution. This study adds to the growing evidence that
      conventional temperate intensively managed lowland grasslands contribute
      significantly to soil erosion and diffuse pollution rates. This is the first
      grassland study to monitor hydrological characteristics and multiple pollutant
      fluxes (suspended sediment [SS] and the macronutrients: total oxidized nitrogen-N
      [TON], total phosphorus [TP], and total carbon [TC]) at high temporal resolution
      (monitoring up to every 15 min) over 1 yr. Monitoring was conducted across three
      fields (6.5-7.5 ha) on the North Wyke Farm Platform, UK. The estimated annual
      erosion rates (up to 527.4 kg ha), TP losses (up to 0.9 kg ha), and TC losses (up
      to 179 kg ha) were similar to or exceeded the losses reported for other
      grassland, mixed land-use, and arable sites. Annual yields of TON (up to 3 kg ha)
      were less than arable land-use fluxes and earlier grassland N studies, an
      important result as the study site is situated within a Nitrate Vulnerable Zone.
      The high-resolution monitoring allowed detailed "system's functioning"
      understanding of hydrological processes, mobilization- transport pathways of
      individual pollutants, and the changes of the relative importance of diffuse
      pollutants through flow conditions and time. Suspended sediment and TP
      concentrations frequently exceeded water quality guidelines recommended by the
      European Freshwater Fisheries Directive (25 mg L) and the European Water
      Framework Directive (0.04 mg soluble reactive P L), suggesting that intensively
      managed grasslands pose a significant threat to receiving surface waters. Such
      sediment and nutrient losses from intensively managed grasslands should be
      acknowledged in land management guidelines and advice for future compliance with
      surface water quality standards. 

PMID- 25602219
TI  - Nitrate-nitrogen export: magnitude and patterns from drainage districts to
      downstream river basins.
AB  - Alteration of the prairie pothole ecosystem through installation of subsurface
      tile drains has enabled the U.S. Corn Belt to become one of the most
      agriculturally productive areas in the world but has also led to increased
      nitrogen losses to surface water. The literature contains numerous field plot
      studies but few in-depth studies of nitrate exports from small, tile-drained
      catchments representative of agricultural drainage districts. The objectives of
      this study were to quantify hydrology and nitrate-nitrogen (NO-N) export patterns
      from three tile-drained catchments and the downstream river over a 5-yr period,
      compare results to prior plot-, field-, and watershed-scale studies, and discuss
      implications for water quality improvement in these landscapes. The tile-drained
      catchments had an annual average water yield of 247 mm yr, a flow-weighted NO-N
      concentration of 17.1 mg L, and an average NO-N loss of nearly 40 kg ha yr.
      Overall, water yields were consistent with prior tile drainage studies in Iowa
      and the upper Midwest, but associated NO-N concentrations and losses were among
      the highest reported for plot studies and higher than those found in small
      watersheds. More than 97% of the nitrate export occurs during the highest 50% of
      flows, at both the small catchment and river basin scale. Findings solidified the
      importance of working at the drainage district scale to achieve nitrate
      reductions necessary to meet water quality goals. They also point to the need for
      implementing strategies that address both hydrology and nitrogen supply in tile
      drained landscapes. 

PMID- 25602220
TI  - Hydrometeorological and physicochemical drivers of fecal indicator bacteria in
      urban stream bottom sediments.
AB  - High levels of fecal indicator bacteria (FIB) are the leading cause of surface
      water quality impairments in the United States. Watershed-scale models are
      commonly used to identify relative contributions of watershed sources and to
      evaluate the effectiveness of remediation strategies. However, most existing
      models simplify FIB transport behavior as equivalent to that of dissolved-phase
      contaminants, ignoring the impacts of sediment on the fate and transport of FIB.
      Implementation of sediment-related processes within existing models is limited by
      minimal available monitoring data on sediment FIB concentrations for model
      development, calibration, and validation purposes. The purpose of the present
      study is to evaluate FIB levels in the streambed sediments as compared to those
      in the water column and to identify environmental variables that influence water
      and underlying sediment FIB levels. Concentrations of and enterococci in the
      water column and sediments of an urban stream were monitored weekly for 1 yr and
      correlated with a variety of potential hydrometeorological and physicochemical
      variables. Increased FIB concentrations in both the water column and sediments
      were most strongly correlated with increased antecedent 24-h rainfall, increased
      stream water temperature, decreased dissolved oxygen, and decreased specific
      conductivity. These observations will support future efforts to incorporate
      sediment-related processes in existing models through the identification of key
      FIB relationships with other model inputs, and the provision of sediment FIB
      concentrations for direct model calibration. In addition, identified key
      variables can be used in quick evaluation of the effectiveness of potential
      remediation strategies. 

PMID- 25602221
TI  - A cost-effective management practice to decrease phosphorus loss from dairy
      farms.
AB  - Phosphorus (P) loss from land can impair surface water quality. A paired
      catchment study was conducted on a grazed dairy farm that tested the hypothesis
      that cultivating and sowing a low-P-requiring grass in near stream areas and high
      P-requiring clover ( L.) elsewhere lost less P to water and was potentially more
      profitable than a mixed grass-clover pasture managed for the cover component. Two
      catchments were treated the same for 2 yr, after which 40% of the treatment
      catchment was cultivated around the stream, sown in ryegrass ( L.) and fertilized
      with 150 kg nitrogen (N) ha yr and 10 kg P ha yr. White clover was established in
      the remainder of the catchment and received no N but 30 kg P ha yr. The control
      catchment received 150 kg N ha yr and 30 kg P ha yr. After the monocultures were
      installed, filterable reactive P and total P concentrations decreased by 44 and
      26% respectively, while the better-quality forage suggested a possible
      improvement in profitability. We concluded that with some caveats (e.g., a 2%
      increase in modeled N loss), using grass-clover monocultures strategically across
      a dairy farm may decrease P loss to surface water and improve profitability
      compared with a mixed pasture. 

PMID- 25602222
TI  - Effects of sewage effluents on water quality in tropical streams.
AB  - Increased urbanization in many tropical regions has led to an increase in
      centralized treatment of sewage effluents. Research regarding the effects of
      these wastewater treatment plants (WWTPs) on the ecology of tropical streams is
      sparse, so we examined the effects of WWTPs on stream water quality on the
      Caribbean island of Puerto Rico. Nutrient concentrations, discharge, dissolved
      oxygen (DO), biochemical oxygen demand (CBOD), and specific UV absorbance (SUVA)
      at 254 nm were measured upstream from the WWTP effluent, at the WWTP effluent,
      and below the WWTP effluent. All parameters measured (except DO) were
      significantly affected by discharge of WWTP effluent to the stream. The values of
      SUVA at 254 nm were typically lower (<2.5 m mg L) in WWTP effluents than those
      measured upstream of the WWTP, suggesting that WWTP effluents are contributing
      labile carbon fractions to receiving streams, thus changing the chemical
      composition of dissolved organic carbon in downstream reaches. Effluents from
      WWTP contributed on average 24% to the stream flow at our tropical streams. More
      than 40% of the nutrient loads in receiving streams came from WWTP effluents,
      with the effects on NO-N and PO-P loads being the greatest. The effect of WWTPs
      on nutrient loads was significantly larger than the effect of flow due to the
      elevated nutrient concentrations in treated effluents. Our results demonstrate
      that inputs from WWTPs to streams contribute substantially to changes in water
      quality, potentially affecting downstream ecosystems. Our findings highlight the
      need to establish nutrient criteria for tropical streams to minimize degradation
      of downstream water quality of the receiving streams. 

PMID- 25602223
TI  - Safety of gardening on lead- and arsenic-contaminated urban brownfields.
AB  - Elevated levels of lead (Pb) and arsenic (As) are not uncommon for urban soils.
      Test plots were established at urban gardens in Tacoma and Seattle, WA. The
      Tacoma site was contaminated with Pb (51-312 mg kg) and As (39-146 mg kg), and
      the Seattle site had high Pb soil concentrations ranging from 506 to 2022 mg kg
      and As concentrations of <20 mg kg. The efficacy of biosolids mix and compost
      amendment in reducing Pb and As concentrations in three vegetables (carrots,
      lettuce, and tomatoes) and the bioaccessibility of soil Pb and As were evaluated.
      Food-chain transfer of Pb and As were evaluated by measuring plant Pb and As
      concentrations after kitchen-style washing, a laboratory cleaning procedure, or
      peeling. The experimental design was a randomized complete block with a split
      plot arrangement. Tacoma site treatments included a Class A biosolids mix (TAGRO)
      with dolomite, and soil at the Seattle site was amended with Cedar-Grove compost
      (CGC) plus dolomite. TAGRO amendment diluted soil Pb by 10 to 23% and As by 12 to
      25% at the Tacoma site, and CGC + dolomite resulted in 20 to 50% dilution in soil
      Pb at the Seattle site. Both amendments reduced Pb concentrations in vegetables
      by 50 to 71%, and As reductions ranged from 46 to 80%. At the Tacoma site, Pb
      concentrations (dry weight basis) in carrots, lettuce, and tomatoes ranged from
      8.89 to 25.0, from 0.37 to 3.83, and from 0.54 to 1.24 mg kg, respectively. Plant
      As concentrations were below 703 MUg kg (dry weight) for the vegetables and
      followed the order lettuce > carrot > tomato. Food-chain transfer of Pb and As in
      vegetables grown in contaminated urban soils were reduced by laboratory cleaning.

PMID- 25602224
TI  - Sorption of tetracycline to varying-sized montmorillonite fractions.
AB  - The influence of particle sizes on sorption of tetracycline by clay minerals is
      poorly understood. In this study, montmorillonite clay fractions with varying
      particle sizes were prepared by successive centrifugation, and the effects of
      particle sizes on sorption of tetracycline were evaluated using an equilibrium
      dialysis method. Sorption isotherms were nearly overlapped for size fractions
      ranging from 6.38 to 16.00 MUm, except for the finest clay fraction (0.41 MUm).
      The relatively low sorption by the fraction with the smallest particles could be
      attributed to the colloidal nature and high edge-to-surface ratio, which could
      lead to reduced accessibility of tetracycline to sorption sites (particularly
      those at the edges). The impact of solution pH and coexisting Na and Ca ions on
      tetracycline sorption was found to differ between the finest fraction and other
      clay fractions. The results demonstrated for the first time that clay particle
      size greatly influenced tetracycline sorption to clay minerals and consequently
      might affect their transport and bioavailability in the environment. 

PMID- 25602225
TI  - Effects of Acidifying Pig Diets on Emissions of Ammonia, Methane, and Sulfur from
      Slurry during Storage.
AB  - Ammonia (NH) volatilization from intensive livestock production is a threat to
      natural ecosystems. This study investigated pig diet manipulation by 1% (w/w)
      benzoic acid (BA) amendment and lowering of dietary electrolyte balance through
      substituting 1.4% (w/w) CaCO with 2.0% (w/w) CaCl. Urine and feces were collected
      separately from 24 pigs fed one of four diets (Control, +BA, +CaCl, +BA+CaCl) in
      metabolic cages and mixed as slurry. During 103 d of storage, all acidifying
      diets consistently reduced pH in the slurry by 0.4 to 0.6 units. There was a
      strong relationship between slurry pH and NH emissions, which were considerably
      reduced by the three acidifying diets. The +BA diet decreased NH emission by 28%,
      the +CaCl diet by 37%, and the combined +BA and +CaCl diet by 40%. Acidifying
      diets had no effect on S cycling or emission of volatile S compounds under the
      prevailing conditions of restricted S feeding. Methane (CH) emissions were
      increased by 73% in diets with CaCl. An initial delay in CH emissions was
      investigated in a separate experiment with manipulation of pH (5.4, 6.7, or 8.8)
      and inoculation with adapted pig slurry (0, 4, 11, or 19%), which showed that
      methanogenic potential, rather than inhibitory effects of the chemical
      environment, caused the delay. In conclusion, NH emissions from slurry could be
      reduced by addition of BA to pig diets or by controlling the dietary electrolyte
      balance, but there was no additive effect of combining the two strategies.
      However, CH emissions from slurry may increase with acidifying diets. 

PMID- 25602226
TI  - Removal of from saturated sand columns supplemented with hydrochar produced from
      maize.
AB  - Despite numerous studies on hydrochar use, its application in water treatment for
      pathogen removal remains unexplored. In this study, we evaluated the efficiency
      of hydrochar produced from crop residue of maize for water treatment by
      determining breakthrough from sand columns supplemented with hydrochar. To
      enhance the adsorptive capacity, raw hydrochar was activated by 1 mol L KOH at
      room temperature. The experiments conducted in a 10-cm sand bed with 1.5% (w/w)
      activated and raw hydrochar supplements, not activated by KOH, showed 93 and 72%
      of removal efficiencies, respectively. Activation of KOH not only enhanced the
      removal but also increased the strength of the attachment: 96% of the retained in
      the column with activated hydrochar supplements was shown to be irreversibly
      attached, compared with only 65% for the raw hydrochar. Scanning electron
      microscopy/energy-dispersive X-ray spectroscopy, Fourier transform infrared
      spectroscopy, and zeta-potential analyses suggested that these improvements were
      mainly due to the development of a well-formed porous surface structure and less
      negative surface charges on the activated hydrochar. 

PMID- 25602227
TI  - Effects of biochar amendments on soil microbial biomass and activity.
AB  - Environmental benefits reported in the literature of using biochar as a soil
      amendment are generally increased microbial activity and reduced greenhouse gas
      (GHG) emissions. This study determined the effects of amendment with biomass
      feedstocks (spent coffee grounds, wood pellets, and horse bedding compost) and
      that of biochars (700 degrees C) produced from these feedstocks on soil microbial
      biomass (C and N) and activity. Soils were amended with these substrates at 0.75%
      by weight and incubated for up to 175 d under laboratory conditions. Biochar
      residual effects on soil microbial activity were also studied by amending these
      soils with either ammonium nitrate (NHNO, 35 mg N kg) or with glucose (864 mg C
      kg) plus NHNO. Soil microbial biomass C and N, net N mineralization, and CO, NO,
      and CH emissions were measured. Amendment with biomass feedstocks significantly
      increased soil microbial biomass and activity, whereas amendment with the
      biochars had no significant effect. Also, biochar amendment had no significant
      effect on either net N mineralization or NO and CH emissions from soil. These
      results indicate that production of biochars at this high temperature eliminated
      potential substrates. Microbial biomass C in biochar-amended and unamended soils
      was not significantly different following additions of NHNO or glucose plus NHNO,
      suggesting that microbial access to otherwise labile C and N was not affected.
      This study shows that biochars produced at 700 degrees C, regardless of feedstock
      source, do not enhance soil microbial biomass or activity. 

PMID- 25602228
TI  - Physical and thermal characteristics of dairy cattle manure.
AB  - Greenhouse and regulated gas emissions from animal waste are naturally mediated
      by moisture content and temperature. As with soils, emissions from manure could
      be readily estimated given the physical, hydraulic, and thermal properties are
      described by models and microbes and nutrients are not limiting factors. The
      objectives of this study were to measure and model physical, hydraulic, and
      thermal properties of dairy manure to support advanced modeling of gas and water
      fluxes in addition to solute, colloid, and heat transport. A series of soil
      science measurement techniques were applied to determine a set of fundamental
      properties of as-excreted dairy cattle manure. Relationships between manure
      dielectric permittivity and volumetric water content (theta) were obtained using
      time-domain reflectometry and capacitance-based dielectric measurements. The
      measured water retention characteristic for cattle manure was similar to organic
      peat soil. The unsaturated hydraulic conductivity function of dairy manure was
      inferred from inverse numerical fitting of laboratory manure evaporation results.
      The thermal properties of dairy manure, including thermal conductivity, thermal
      diffusivity, and bulk volumetric heat capacity, were also determined using three
      penta-needle heat pulse probes. The accuracy of the heat capacity measurements
      was determined from a comparison of theoretical theta, estimated from the
      measured thermal properties with that determined by the capacitance-based
      dielectric measurement. These data represent a novel and unique contribution for
      advancing prediction and modeling capabilities of gas emissions from cattle
      manure, although the uncertainties associated with the complexities of shrinkage,
      surface crust formation, and cracking must also be considered. 

PMID- 25602229
TI  - Mechanisms of ammonium transformation and loss in intermittently aerated
      leachfield soil.
AB  - Optimization of N removal in soil-based wastewater treatment systems requires an
      understanding of the microbial processes involved in N transformations. We
      examined the fate of NH in intermittently aerated leachfield mesocosms over a 24
      h period. Septic tank effluent (STE) was amended with NHCl to help determine N
      speciation and distribution in drainage water, soil, and headspace gases. Our
      results show that 5.7% of the N was found in soil, 10.0% in drainage water, and
      84.3% in the gas pool. Ammonium accounted for 41.7% of the soil N pool, followed
      by NO (29.2%), organic N (21.7%), and microbial biomass N (7.5%). In drainage
      water, NO constituted ~80% of the N pool, whereas NH was absent from this pool.
      Nitrous oxide was the dominant form of N in the gas phase 6 h after addition of
      NH-amended STE to the mesocosms, after which its mass declined exponentially; by
      contrast, the mass of N was initially low but increased linearly with time to
      become the dominant form of N after 24 h. Analysis based on the isotopic
      enrichment of NO and N indicates that nitrification contributed 98.8 and 23.1% of
      the NO flux after 6 and 24 h, respectively. Our results show that gaseous losses
      are the main mechanism for NH removal from wastewater in intermittently aerated
      soil. In addition, nitrification, which is generally not considered a significant
      pathway for N loss in soil-based wastewater treatment, is an important source
      process for NO. 

PMID- 25602230
TI  - Nitrogen in stored poultry litter: uric Acid and xanthine.
AB  - Laboratory incubations of four broiler litter (BL) samples at 30 degrees C were
      performed to investigate the effect of water content on the decay of uric acid
      nitrogen (UAN) and xanthine nitrogen (XN). UAN and XN concentrations increased in
      all samples during a period of 1 to 8 d before declining for the remaining 30 d.
      The increases may be the result of guanine and adenine catabolism. The slopes of
      linear equations fit to the natural log of the observations from 16 sampling
      points over 38 d were compared using the GLM procedure in SAS and results
      indicate that both UAN and XN decay significantly ( = 0.05) more rapidly with
      increasing water content (theta). A second study showed significant effects in
      one of three samples on the decay rate of UAN with additions of flue-gas
      desulfurization (FGD) gypsum or alum at a water content of 750 g kg BL. The decay
      rate of XN was not significantly affected. Finally, a simple two-point sampling
      study on the effect of water potential for the estimation of first order rate
      equation constants showed a positive relationship between the rate of UAN and XN
      decay over 28 d as a function of water potential (psi): UAN = 0.0054 * psi +
      0.1010 ( = 0.9987) and XN = 0.0066 * psi + 0.1101 ( = 0.9285). This is the first
      study of UAN and XN decay in BL and the findings add to our understanding of
      mineralizable N from BL. 

PMID- 25602231
TI  - Sources of variation in home lawn soil nitrogen dynamics.
AB  - Urban, suburban, and exurban lawns are an increasingly important ecosystem type
      in the United States. There is great concern about the environmental performance
      of lawns, especially nitrate (NO) leaching and nitrous oxide (NO) flux associated
      with nitrogen (N) fertilizer use. Previous studies of lawn N dynamics have
      produced conflicting results, with some studies showing high NO leaching and NO
      flux and others showing lower losses and high retention and cycling of N inputs.
      We hypothesized that this variation is caused by differences in lawn management
      and soil properties that control root and soil organic matter (SOM) dynamics that
      influence N cycling processes. We tested these hypotheses by making measurements
      of soil NO, root biomass, rates of potential net N mineralization and
      nitrification, NO flux, and SOM levels in samples from the front and backyards of
      residential homes in suburban and exurban neighborhoods with contrasting soil
      types in the Baltimore metropolitan area. There were no differences between front
      and backyards, between suburban and exurban neighborhoods, or between different
      soil types. Further, there were no significant relationships between root
      biomass, SOM, soil NO levels, and NO fluxes. These results suggest that lawns
      have uniformly high rates of plant productivity that underlies high levels of SOM
      and N retention in these ecosystems across the Baltimore metropolitan area. 

PMID- 25602232
TI  - Charging up batteries.

PMID- 25602235
TI  - Subjective versus objective accommodative amplitude: preschool to presbyopia.
AB  - PURPOSE: This study compared subjective and objective accommodative amplitudes to
      characterize changes from preschool to presbyopia. METHODS: Monocular
      accommodative amplitude was measured with three techniques in random order
      (subjective push-up, objective minus lens stimulated, and objective proximal
      stimulated) on 236 subjects aged 3 to 64 years using a 1.5-mm letter. Subjective
      push-up amplitudes were the dioptric distance at which the target first blurred
      along a near-point rod. Objective minus lens stimulated amplitudes were the
      greatest accommodative response obtained by Grand Seiko autorefraction as
      subjects viewed the stimulus at 33 cm through increasing minus lens powers.
      Objective proximal stimulated amplitudes were the greatest accommodative response
      obtained by Grand Seiko autorefraction as subjects viewed the stimulus at
      increasing proximity from 40 cm up to 3.33 cm. RESULTS: In comparison with
      subjective push-up amplitudes, objective amplitudes were lower at all ages, with
      the most dramatic difference occurring in the 3- to 5-year group (subjective push
      up, 16.00 +/- 4.98 diopters [D] vs. objective proximal stimulated, 7.94 +/- 2.37
      D, and objective lens stimulated, 6.20 +/- 1.99 D). Objective proximal and lens
      stimulated amplitudes were largest in the 6- to 10-year group (8.81 +/- 1.24 D
      and 8.05 +/- 1.82 D, respectively) and gradually decreased until the fourth
      decade of life when a rapid decline to presbyopia occurred. There was a
      significant linear relationship between objective techniques (y = 0.74 + 0.96x,
      R2 = 0.85, p < 0.001) with greater amplitudes measured for the proximal
      stimulated technique (mean difference, 0.55 D). CONCLUSIONS: Objective
      measurements of accommodation demonstrate that accommodative amplitude is
      substantially less than that measured by the subjective push-up technique,
      particularly in young children. These findings have important clinical
      implications for the management of uncorrected hyperopia.

PMID- 25602238
TI  - Letter to the editor: Test-retest reliability of retinal oxygen saturation
      measurement.

PMID- 25602239
TI  - Authors' response.

PMID- 25602241
TI  - Computerized and on-line neuropsychological testing for late-life cognition and
      neurocognitive disorders: are we there yet?
AB  - PURPOSE OF REVIEW: Cost-effective, valid, efficient and accessible tests for the
      detection of late-life neurocognitive disorders are crucial, as early
      identification facilitates appropriate early intervention. Proponents of
      computerized neuropsychological assessment devices (CNADs) assert that technology
      based assessments improve upon traditional neuropsychological tests. However,
      there remain fundamental questions of validity, reliability, normative data and
      administration, raising the question of whether CNADs are appropriate
      alternatives. RECENT FINDINGS: Since publication of the 2012 American Academy of
      Clinical Neuropsychology and National Academy of Neuropsychology joint position
      paper outlining appropriate standards for CNAD development, the field has not
      significantly advanced, with the majority of recommendations inadequately
      addressed. SUMMARY: Whilst there is a pressing need for innovative and readily
      applicable cognitive tests, these requirements do not outweigh the necessity for
      valid measures. Overall, the psychometric quality, standardization, normative
      data and administration advice of CNADs for neurocognitive disorders are lacking.
      Therefore, the risk of diagnostic errors is potentially high and poor clinical
      decisions could potentially arise, having significant impact upon individuals in
      terms of their well being and access to treatment. We recommend clinicians and
      researchers make informed decisions about CNAD suitability for their clients and
      their individual requirements based upon published psychometric and other test
      information.

PMID- 25602242
TI  - Nutritional supplementation for Alzheimer's disease?
AB  - PURPOSE OF REVIEW: Evidence for the benefit of nutrition in Alzheimer's disease
      continues to accumulate. Many studies with individual vitamins or supplements
      show marginal, if any, benefit. However, new findings with combinatorial
      formulations demonstrate improvement in cognitive performance and behavioral
      difficulties that accompany Alzheimer's disease. Herein, we review some of the
      most recent clinical advances and summarize supportive preclinical studies.
      RECENT FINDINGS: We present novel positive effects on Alzheimer's disease derived
      from diet, trace elements, vitamins and supplements. We discuss the inherent
      difficulty in conducting nutritional studies because of the variance in
      participants' nutritional history, versus pharmacological interventions in which
      participants are naive to the intervention. We examine the evidence that
      epigenetics play a role in Alzheimer's disease and how nutritional intervention
      can modify the key epigenetic events to maintain or improve cognitive
      performance. SUMMARY: Overall consideration of the most recent collective
      evidence suggests that the optimal approach for Alzheimer's disease would seem to
      combine early, multicomponent nutritional approaches (a Mediterranean-style diet,
      multivitamins and key combinatorial supplements), along with lifestyle
      modifications such as social activity and mental and physical exercise, with
      ultimate addition of pharmacological agents when warranted.

PMID- 25602245
TI  - Advances in the treatment of tuberous sclerosis complex.
AB  - PURPOSE OF REVIEW: Tuberous sclerosis complex (TSC) is a multisystem genetic
      disorder with physical and neuropsychiatric manifestations and significant
      research progress has been made in recent years. Here, we focus on the key
      advances over the last 18 months. RECENT FINDINGS: Three main themes were
      identified in the literature. Firstly, the diagnostic criteria and surveillance
      guidelines for TSC were revised, incorporating a genetic criterion alongside
      clinical criteria, and making a positive step towards evidence-based treatment of
      TSC. Secondly, a new term - TSC-associated neuropsychiatric disorders (TAND) -
      was introduced as an umbrella term for all possible neuropsychiatric difficulties
      seen in TSC, and a TAND Checklist was developed as a screening tool. Thirdly, the
      risks and benefits of molecularly targeted treatments of the neuropsychiatric
      manifestations of TSC are being debated. SUMMARY: The updated diagnostic criteria
      and management guidelines, the new concept of TAND and the TAND Checklist should
      lead to significant improvements in the quality of care for individuals with TSC.
      The promise of mammalian target of rapamycin inhibitors and other molecular
      treatments are still to be confirmed. We suggest that great care should be taken
      to identify 'optimal mammalian target of rapamycin signalling' in the therapeutic
      approach to the neuropsychiatric features of the disorder.

PMID- 25602243
TI  - Brain imaging research in autism spectrum disorders: in search of neuropathology
      and health across the lifespan.
AB  - PURPOSE OF REVIEW: Advances in brain imaging research in autism spectrum
      disorders (ASD) are rapidly occurring, and the amount of neuroimaging research
      has dramatically increased over the past 5 years. In this review, advances during
      the past 12 months and longitudinal studies are highlighted. RECENT FINDINGS:
      Cross-sectional neuroimaging research provides evidence that the neural
      underpinnings of the behavioral signs of ASD involve not only dysfunctional
      integration of information across distributed brain networks but also basic
      dysfunction in primary cortices.Longitudinal studies of ASD show abnormally
      enlarged brain volumes and increased rates of brain growth during early childhood
      in only a small minority of ASD children. There is evidence of disordered
      development of white matter microstructure and amygdala growth, and at 2 years of
      age, network inefficiencies in posterior cerebral regions.From older childhood
      into adulthood, atypical age-variant and age-invariant changes in the
      trajectories of total and regional brain volumes and cortical thickness are
      apparent at the group level. SUMMARY: There is evidence of abnormalities in
      posterior lobes and posterior brain networks during the first 2 years of life in
      ASD and, even in older children and adults, dysfunction in primary cortical
      areas.

PMID- 25602246
TI  - Inflammation and neurodegenerative disorders: is there still hope for therapeutic
      intervention?
AB  - PURPOSE OF REVIEW: This review aims to describe the current understanding of
      neuroinflammation in neurodegeneration and evaluate the value of various anti
      inflammatory treatments. RECENT FINDINGS: Inflammation plays important roles in
      common disease such as dementia and depression. Underlying mechanisms including
      the role of inflammasomes in these diseases have been recently described.
      Interventions using Omega-3 polyunsaturated fatty acids, NSAIDs and targeted
      antagonists (e.g., etanercept) show no convincing clinical efficacy in
      inflammation-associated depression, cognitive decline and dementia. SUMMARY:
      Therapeutic targeting of inflammation appears to be relevant in brain conditions
      characterized by neuroinflammation and neurodegeneration, although published anti
      inflammatory interventions have shown no relevant clinical efficacy. Newly
      described pharmacological targets in the neuroinflammation pathways may not only
      offer a more profound understanding of the underlying pathophysiology but also
      raise hope for the development of novel pharmacological agents.

PMID- 25602247
TI  - Accelerating Alzheimer's research through 'natural' animal models.
AB  - PURPOSE OF REVIEW: Alzheimer's disease is a complex multifactorial age-related
      neurodegenerative disorder. Current transgenic animal models do not fully
      recapitulate human Alzheimer's disease at the molecular, cellular and behavioural
      levels. This review aims to address the clinical relevance of using
      'physiologically' aged rats, dogs and Octodon degus, as more representative
      'natural' ecologically valid models to elucidate mechanistic aspects of
      Alzheimer's disease, and for the development of therapeutic agents to attenuate
      age-related cognitive decline. RECENT FINDINGS: Aged rats, dogs and O. degus
      decline cognitively and ultimately develop Alzheimer's disease-like symptoms in
      response to the natural ageing process. Aged rats provide a tractable and popular
      model to examine the neurobiological basis underlying cognitive decline with age,
      but they do not develop Alzheimer's disease pathology. Progressive accumulation
      of abnormal amyloid-beta in extracellular plaques and surrounding cerebral
      vasculature is a common feature in human Alzheimer's disease, aged canine model
      and most nonhuman primates. Interestingly, the O. degus develops amyloid-beta
      deposits, neurofibrillary tangles containing hyperphosphorylated tau protein,
      altered cholinergic transmission and cognitive deficits analogous to those
      observed in Alzheimer's disease. Natural animal models better represent the full
      pathophysiology of Alzheimer's disease and are not only a viable alternative to
      transgenic models, but also are arguably the preferable model. SUMMARY: 'Natural'
      models are useful to elucidate the neurobiological basis of Alzheimer's disease
      and develop effective therapeutic strategies that can be translated into human
      clinical trials.

PMID- 25602248
TI  - An update on pharmacotherapy for autism spectrum disorder in children and
      adolescents.
AB  - PURPOSE OF REVIEW: Although there is no known efficacious pharmacotherapy for
      core symptoms of autism spectrum disorder (ASD), psychotropic medications are
      commonly prescribed for behavioral/emotional symptoms associated with ASD. We
      reviewed current evidence-based pharmacotherapy options and updates from recent
      noteworthy studies. RECENT FINDINGS: Atypical antipsychotics, particularly
      risperidone and aripiprazole, are effective in reducing irritability, stereotypy
      and hyperactivity. Metabolic adverse events, including weight gain and
      dyslipidemia, are common. Methylphenidate is effective in reducing attention
      deficit hyperactivity disorder (ADHD) symptoms. Atomoxetine and alpha-2 agonists
      appear effective in reducing ADHD symptoms. Selective serotonin reuptake
      inhibitors are not effective in improving repetitive behaviors in children with
      ASD, and frequently cause activating adverse events. Efficacy of antiepileptic
      drugs is inconclusive. Overall, efficacy and tolerability of pharmacotherapy in
      children with ASD are less favorable than data seen in typically developing
      children with similar symptoms. Newer agents, including glutamatergic agents and
      oxytocin, appear promising albeit with mixed results. SUMMARY: Current evidence
      based pharmacotherapy options in children with ASD are very limited, and many
      have substantial adverse events. Clinicians should use pharmacotherapy as a part
      of comprehensive treatment, and judiciously weigh risks and benefits. New
      pharmacotherapy options for core symptoms as well as co-occurring symptoms of ASD
      are in urgent need.

PMID- 25602249
TI  - An update on anxiety in youth with autism spectrum disorders.
AB  - PURPOSE OF REVIEW: Anxiety is one of the most common co-occurring psychiatric
      conditions in youth with autism spectrum disorders (ASDs). This article reviews
      recent evidence as well as earlier relevant studies regarding the
      characteristics, assessment, and treatment of anxiety in youth with ASD. RECENT
      FINDINGS: It is well established that the prevalence of anxiety in youth with an
      ASD is significantly greater than the prevalence of anxiety in the general
      population. Recent studies have highlighted the importance of informant, method,
      and instrument when measuring anxiety in this population. Despite the high
      prevalence, findings to date have been unable to identify any consistent risk
      factors for anxiety. New psychological treatments, including modified cognitive
      behavioral therapy for youth with high functioning ASD and co-occurring anxiety,
      are emerging. Pharmacological data, however, are scant. Existing studies show
      that youth with ASD are at increased risk for behavioral activation when taking
      SSRIs. SUMMARY: Clinicians working with youth with ASD are encouraged to
      routinely screen for anxiety. Until further data are available, clinical judgment
      is needed when prescribing treatments, particularly selective serotonin reuptake
      inhibitors, which require close monitoring of side-effects. Research on risk
      factors, pathophysiology, and treatment of this condition is needed.

PMID- 25602251
TI  - Sexual behavior and its correlates after traumatic brain injury.
AB  - PURPOSE OF REVIEW: Traumatic brain injury (TBI) is one of the leading causes of
      permanent disability in young adults and is frequently accompanied by changes in
      sexual behaviors. Satisfying sexuality is an important factor for overall quality
      of life in people with disabilities. The purpose of this article is to review the
      studies evaluating the assessment, correlates and management of sexuality
      following TBI. RECENT FINDINGS: The Brain Injury Questionnaire of Sexuality is
      the first validated questionnaire specifically developed for adults with TBI. A
      considerable amount of individuals with TBI show inappropriate sexual behaviors
      and sexual dysfunctions. Whereas inappropriate sexual behaviors are related to
      younger age, less social participation and more severe injuries, sexual
      dysfunctions show an association with higher fatigue, higher depression scores,
      less self-esteem and female sex. Healthcare professionals have suggested that
      because of discomfort at the individual or institutional level, sexual problems
      are often not sufficiently addressed and have suggested that a specialist should
      treat sexual problems. SUMMARY: Although some important correlates of sexual
      problems could be identified, methodological differences across studies limit
      their comparability. Furthermore, there is an absence of evidence-based treatment
      strategies for addressing sexual problems. Therapeutic efforts should take into
      account the identified correlates of sexual problems following TBI.

PMID- 25602250
TI  - Treatment of the psychiatric problems associated with fragile X syndrome.
AB  - PURPOSE OF REVIEW: This work reviews recent research regarding treatment of
      fragile X syndrome (FXS), the most common inherited cause of intellectual
      disability and autism spectrum disorder. The phenotype includes anxiety linked to
      sensory hyperarousal, hyperactivity, and attentional problems consistent with
      attention deficit hyperactivity disorder and social deficits leading to autism
      spectrum disorder in 60% of boys and 25% of girls with FXS. RECENT FINDINGS:
      Multiple targeted treatments for FXS have rescued the phenotype of the fmr1
      knockout mouse, but few have been beneficial to patients with FXS. The failure of
      the metabotropic glutamate receptor 5 antagonists falls on the heels of the
      failure of Arbaclofen's efficacy in children and adults with autism or FXS. In
      contrast, efficacy has been demonstrated in a controlled trial of minocycline in
      children with FXS. Minocycline lowers the abnormally elevated levels of matrix
      metalloproteinase 9 in FXS. Acamprosate and lovastatin have been beneficial in
      open-label trials in FXS. The first 5 years of life may be the most efficacious
      time for intervention when combined with behavioral and/or educational
      interventions. SUMMARY: Minocycline, acamprosate, lovastatin, and sertraline are
      treatments that can be currently prescribed and have shown benefit in children
      with FXS. Use of combined medical and behavioral interventions will likely be
      most efficacious for the treatment of FXS.

PMID- 25602252
TI  - Advances in therapeutic interventions for neurodevelopmental disorders.

PMID- 25602253
TI  - Mesenchymal stem cells engrafted in a fibrin scaffold stimulate Schwann cell
      reactivity and axonal regeneration following sciatic nerve tubulization.
AB  - The present study investigated the effectiveness of mesenchymal stem cells (MSCs)
      associated with a fibrin scaffold (FS) for the peripheral regenerative process
      after nerve tubulization. Adult female Lewis rats received a unilateral sciatic
      nerve transection followed by repair with a polycaprolactone (PCL)-based tubular
      prosthesis. Sixty days after injury, the regenerated nerves were studied by
      immunohistochemistry. Anti-p75NTR immunostaining was used to investigate the
      reactivity of the MSCs. Basal labeling, which was upregulated during the
      regenerative process, was detected in uninjured nerves and was significantly
      greater in the MSC-treated group. The presence of GFP-positive MSCs was detected
      in the nerves, indicating the long term survival of such cells. Moreover, there
      was co-localization between MSCs and BNDF immunoreactivity, showing a possible
      mechanism by which MSCs improve the reactivity of SCs. Myelinated axon counting
      and morphometric analyses showed that MSC engrafting led to a higher degree of
      fiber compaction combined with a trend of increased myelin sheath thickness, when
      compared with other groups. The functional result of MSC engrafting was that the
      animals showed higher motor function recovery at the seventh and eighth week
      after lesion. The findings herein show that MSC+FS therapy improves the nerve
      regeneration process by positively modulating the reactivity of SCs. 

PMID- 25602254
TI  - A low-cost, hands-on module to characterize antimicrobial compounds using an
      interdisciplinary, biophysical approach.
AB  - We have developed a hands-on experimental module that combines biology
      experiments with a physics-based analytical model in order to characterize
      antimicrobial compounds. To understand antibiotic resistance, participants
      perform a disc diffusion assay to test the antimicrobial activity of different
      compounds and then apply a diffusion-based analytical model to gain insights into
      the behavior of the active antimicrobial component. In our experience, this
      module was robust, reproducible, and cost-effective, suggesting that it could be
      implemented in diverse settings such as undergraduate research, STEM (science,
      technology, engineering, and math) camps, school programs, and laboratory
      training workshops. By providing valuable interdisciplinary research experience
      in science outreach and education initiatives, this module addresses the paucity
      of structured training or education programs that integrate diverse scientific
      fields. Its low-cost requirements make it especially suitable for use in resource
      limited settings. 

PMID- 25602255
TI  - A meta-analysis of high dose, intermittent vitamin D supplementation among older
      adults.
AB  - BACKGROUND: The effects of intermittent, high dose vitamin D treatment in older
      adults have not been documented. We conducted a meta-analysis to provide a
      quantitative assessment of the efficiency of intermittent, high dose vitamin D
      treatment on falls, fractures, and mortality among older adults. METHODS:
      Electronic databases were searched for randomized controlled trials (RCTs) on
      high dose, intermittent vitamin D supplementation among older adults. Two
      researchers independently screened the literature according to specified
      inclusive and exclusive criteria to extract the data. Meta-analysis was performed
      by using Review Manager 5.1.0 software. RESULTS: Nine trials were included in
      this meta-analysis. High dose, intermittent vitamin D therapy did not decrease
      all-cause mortality among older adults. The risk ratio (95% CI) was 1.04 (0.91
      1.17). No benefit was seen in fracture or fall prevention. The risk ratio for hip
      fractures (95% CI) was 1.17 (0.97-1.41) while for non-vertebral fractures (95%
      CI) it was 1.06 (0.91-1.22), and the risk ratio for falls (95% CI) was 1.02 (0.96
      1.08). Results remained robust after sensitivity analysis. CONCLUSION:
      Supplementation of intermittent, high dose vitamin D may not be effective in
      preventing overall mortality, fractures, or falls among older adults. The route
      of administration of vitamin D supplements may well change the physiological
      effects.

PMID- 25602256
TI  - Quantification and qualification of bacteria trapped in chewed gum.
AB  - Chewing of gum contributes to the maintenance of oral health. Many oral diseases,
      including caries and periodontal disease, are caused by bacteria. However, it is
      unknown whether chewing of gum can remove bacteria from the oral cavity. Here, we
      hypothesize that chewing of gum can trap bacteria and remove them from the oral
      cavity. To test this hypothesis, we developed two methods to quantify numbers of
      bacteria trapped in chewed gum. In the first method, known numbers of bacteria
      were finger-chewed into gum and chewed gums were molded to standard dimensions,
      sonicated and plated to determine numbers of colony-forming-units incorporated,
      yielding calibration curves of colony-forming-units retrieved versus finger
      chewed in. In a second method, calibration curves were created by finger-chewing
      known numbers of bacteria into gum and subsequently dissolving the gum in a
      mixture of chloroform and tris-ethylenediaminetetraacetic-acid (TE)-buffer. The
      TE-buffer was analyzed using quantitative Polymerase-Chain-Reaction (qPCR),
      yielding calibration curves of total numbers of bacteria versus finger-chewed in.
      Next, five volunteers were requested to chew gum up to 10 min after which numbers
      of colony-forming-units and total numbers of bacteria trapped in chewed gum were
      determined using the above methods. The qPCR method, involving both dead and live
      bacteria yielded higher numbers of retrieved bacteria than plating, involving
      only viable bacteria. Numbers of trapped bacteria were maximal during initial
      chewing after which a slow decrease over time up to 10 min was observed. Around
      10(8) bacteria were detected per gum piece depending on the method and gum
      considered. The number of species trapped in chewed gum increased with chewing
      time. Trapped bacteria were clearly visualized in chewed gum using scanning
      electron-microscopy. Summarizing, using novel methods to quantify and qualify
      oral bacteria trapped in chewed gum, the hypothesis is confirmed that chewing of
      gum can trap and remove bacteria from the oral cavity.

PMID- 25602257
TI  - Clinical manifestations of non-O1 Vibrio cholerae infections.
AB  - BACKGROUND: Infections caused by non-O1 Vibrio cholera are uncommon. The aim of
      our study was to investigate the clinical and microbiological characteristics of
      patients with non-O1 V. cholera infections. METHODS: The clinical charts of all
      patients with non-O1 V. cholera infections and who were treated in two hospitals
      in Taiwan were retrospectively reviewed. RESULTS: From July 2009 to June 2014, a
      total of 83 patients with non-O1 V. cholera infections were identified based on
      the databank of the bacteriology laboratories of two hospitals. The overall mean
      age was 53.3 years, and men comprised 53 (63.9%) of the patients. Liver cirrhosis
      and diabetes mellitus were the two most common underlying diseases, followed by
      malignancy. The most common type of infection was acute gastroenteritis (n = 45,
      54.2%), followed by biliary tract infection (n = 12, 14.5%) and primary
      bacteremia (n = 11, 13.3%). Other types of infection, such as peritonitis (n = 5,
      6.0%), skin and soft tissue infection (SSTI) (n = 5, 6.0%), urinary tract
      infection (n = 3, 3.6%) and pneumonia (2, 2.4%), were rare. July and June were
      the most common months of occurrence of V. cholera infections. The overall in
      hospital mortality of 83 patients with V. cholera infections was 7.2%, but it was
      significantly higher for patients with primary bacteremia, hemorrhage bullae,
      acute kidney injury, acute respiratory failure, or admission to an ICU.
      Furthermore, multivariate analysis showed that in-hospital mortality was
      significantly associated with acute respiratory failure (odds ratio, 60.47; 95%
      CI, 4.79-763.90, P = 0.002). CONCLUSIONS: Non-O1 V. cholera infections can cause
      protean disease, especially in patients with risk factors and during warm-weather
      months. The overall mortality of 83 patients with non-O1 V. cholera infections
      was only 7.2%; however, this value varied among different types of infection.

PMID- 25602258
TI  - The association between NQO1 Pro187Ser polymorphism and bladder cancer
      susceptibility: a meta-analysis of 15 studies.
AB  - BACKGROUND:  NAD(P)H: quinone oxidoreductase 1 (NQO1), an obligate two-electron
      reductase, plays an important role in reducing reactive quinones to less reactive
      and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its
      enzyme function may be considered as putative risk factor for cancer. Numerous
      studies have been performed to investigate the association between NQO1 Pro187Ser
      polymorphism and bladder cancer risk; nevertheless, the results remain
      controversial. METHODS: We indentified eligible publications from PubMed, Embase
      and CBM databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs)
      were used to access the strength of the associations. False-positive report
      probability (FPRP) analysis was also performed for all statistically significant
      findings. RESULTS: We collected a total of 15 studies including 4298 cases and
      4275 controls in the final meta-analysis. Overall, the NQO1 187Ser carriers were
      associated with an increased bladder cancer risk (homozygous: OR = 1.43, 95% CI =
      1.08-1.90; recessive: OR = 1.33, 95% CI = 1.03-1.72; dominant: OR = 1.19, 95% CI
      = 1.04-1.37, and allele comparing: OR = 1.18, 95% CI = 1.06-1.33). Stratification
      analyses showed a statistically significant association among Asians (homozygous:
      OR = 1.82, 95% CI = 1.39-2.38; recessive: OR = 1.52, 95% CI = 1.20-1.93,
      dominant: OR = 1.40, 95% CI = 1.05-1.88, and allele comparing: OR = 1.35, 95% CI
      = 1.15-1.58), never smokers (homozygous: OR = 2.30, 95% CI = 1.14-4.65;
      heterozygous: OR = 2.26, 95% CI = 1.43-3.56; dominant model: OR = 1.59, 95% CI =
      1.14-2.21, and allele comparing: OR = 1.72, 95% CI = 1.27-2.33), hospital-based
      studies (homozygous: OR = 1.46, 95% CI = 1.09-1.94; recessive: OR = 1.32, 95% CI
      = 1.02-1.69; dominant: OR = 1.28, 95% CI = 1.05-1.56, and allele comparing: OR =
      1.24, 95% CI = 1.07-1.43), studies with genotyping performed by PCR-RFLP under
      all genetic models, and studies with minor allele frequency >0.30 (homozygous: OR
      = 1.69, 95% CI = 1.25-2.27; recessive: OR = 1.46, 95% CI = 1.10-1.95, and allele
      comparing: OR = 1.25, 95% CI = 1.04-1.51), respectively. CONCLUSIONS: Despite
      some limitations, our meta-analysis provides sufficient evidence that NQO1
      Pro187Ser polymorphism may contribute to bladder cancer risk. These findings need
      further validation in well-designed prospective studies with larger sample size
      and different ethnicities, especially for Asians.

PMID- 25602260
TI  - Electrophilic halogenation-reductive elimination chemistry of organopalladium and
      -platinum complexes.
AB  - CONSPECTUS: Transition metal-catalyzed organic transformations often reveal
      competing reaction pathways. Determining the factors that control the selectivity
      of such reactions is of extreme importance for the design of reliable synthetic
      protocols. Herein, we present the account of our studies over the past decade
      aimed at understanding the selectivity of reductive elimination chemistry of
      organotransition metal complexes under electrophilic halogenation conditions.
      Much of our effort has focused on finding the conditions for selective formation
      of carbon (aryl)-halogen bonds in the presence of competing C-C reductive
      elimination alternatives. In most cases, the latter was the thermodynamically
      preferred pathway; however, we found that the reactions could be diverted toward
      the formation of aryl-iodine and aryl-bromine bonds under kinetic conditions. Of
      particular importance was to maintain the complex geometry that prohibits C-C
      elimination while allowing for the elimination of carbon-halogen bonds. This was
      achieved by employing sterically rigid diphosphine ligands which prevented
      isomerization within a series of Pt(IV) complexes. It was also important to
      understand that the neutral M(IV) products often observed or isolated in the
      oxidative addition reactions are not necessarily the intermediates in the
      reductive elimination chemistry as it generally takes place from unsaturated
      species formed en route to relatively stable M(IV) complexes. While aryl-halide
      reductive elimination for heavier halogens can be competitive with aryl-aryl
      coupling in diaryl M(IV) complexes, the latter reaction always prevails over aryl
      fluoride bond formation. Even when one of the aryl groups is a part of a rigid
      cyclometalated ligand C-C coupling is still the dominant reaction pathway.
      However, when one of the aryl groups is replaced with a phenolate donor aryl-F
      bond formation becomes preferred over C-O bond elimination. During our studies,
      other interesting reactions have been discovered. For example, the fluorination
      of the C(sp(3))-H bond can be very selective and compete favorably with C-C
      coupling. Also, in electron-poor complexes, metal oxidation can have higher
      energy than oxidation of the coordinated iodo ligand resulting in I-F elimination
      instead of the formation of aryl-I bond. Overall, electrophilic fluorination can
      lead to often very selective elimination reactions giving new C-C, C-I, C-F, or I
      F bonds, with this selectivity dependent on the metal center, supporting ligands,
      complex geometry, and electrophilic fluorine source. Together with the many
      reports on the halogenation of organometallic compounds that appeared in recent
      years, our results contribute to understanding the requirements for selective
      transformations under electrophilic conditions and design of new synthetic
      methods for making organohalogen compounds.

PMID- 25602259
TI  - Emerging role of linker histone variant H1x as a biomarker with prognostic value
      in astrocytic gliomas. A multivariate analysis including trimethylation of H3K9
      and H4K20.
AB  - Although epigenetic alterations play an essential role in gliomagenesis, the
      relevance of aberrant histone modifications and the respective enzymes has not
      been clarified. Experimental data implicates histone H3 lysine (K)
      methyltransferases SETDB1 and SUV39H1 into glioma pathobiology, whereas linker
      histone variant H1.0 and H4K20me3 reportedly affect prognosis. We investigated
      the expression of H3K9me3 and its methyltransferases along with H4K20me3 and H1x
      in 101 astrocytic tumors with regard to clinicopathological characteristics and
      survival. The effect of SUV39H1 inhibition by chaetocin on the proliferation,
      colony formation and migration of T98G cells was also examined. SETDB1 and
      cytoplasmic SUV39H1 levels increased from normal brain through low-grade to high
      grade tumors, nuclear SUV39H1 correlating inversely with grade. H3K9me3
      immunoreactivity was higher in normal brain showing no association with grade,
      whereas H1x and H4K20me3 expression was higher in grade 2 than in normal brain or
      high grades. These expression patterns of H1x, H4K20me3 and H3K9me3 were verified
      by Western immunoblotting. Chaetocin treatment significantly reduced
      proliferation, clonogenic potential and migratory ability of T98G cells. H1x was
      an independent favorable prognosticator in glioblastomas, this effect being
      validated in an independent set of 66 patients. Diminished nuclear SUV39H1
      expression adversely affected survival in univariate analysis. In conclusion,
      H4K20me3 and H3K9 methyltransferases are differentially implicated in astroglial
      tumor progression. Deregulation of H1x emerges as a prognostic biomarker. 

PMID- 25602261
TI  - Self-assembly of PEI/SiO2 on polyethylene separators for Li-ion batteries with
      enhanced rate capability.
AB  - A simple and environmentally friendly self-assembly process of oppositely charged
      polymer PEI and inorganic oxide SiO2 was demonstrated for the construction of an
      ultrathin layer on the surface of PE separator. The XPS, FT-IR, SEM, and EDS
      characterizations give clear evidence of the successful self-assembly of PEI and
      SiO2 without significantly increasing the thickness and sacrificing the pristine
      porous structure of PE separator. This process improves a variety of crucial
      properties of PE separator such as the electrolyte wetting, the electrolyte
      uptake, the thermal stability, the ionic conductivity, Li+ transference number,
      the electrochemical stability and the compatibility with lithium electrode,
      endowing lithium-ion battery (Li as anode and LiCoO2 as cathode) with excellent
      capacity retention at high C-rates and superior cycling performance. At the
      current density of 5 C, the cell with PE separator almost loses all the capacity.
      In contrast, the cell with (PEI/SiO2)-modified PE separator still holds 45.2% of
      the discharge capacity at 0.2 C. The stabilized SEI formation and high Li+
      transference number of (PEI/SiO2)-modified PE separator were interpreted to be
      the substantial reasons leading to the remarkably enhanced battery performance,
      rendering some new insights into the role of the separator in lithium-ion
      batteries.

PMID- 25602263
TI  - Inertial sensor self-calibration in a visually-aided navigation approach for a
      micro-AUV.
AB  - This paper presents a new solution for underwater observation, image recording,
      mapping and 3D reconstruction in shallow waters. The platform, designed as a
      research and testing tool, is based on a small underwater robot equipped with a
      MEMS-based IMU, two stereo cameras and a pressure sensor. The data given by the
      sensors are fused, adjusted and corrected in a multiplicative error state Kalman
      filter (MESKF), which returns a single vector with the pose and twist of the
      vehicle and the biases of the inertial sensors (the accelerometer and the
      gyroscope). The inclusion of these biases in the state vector permits their self
      calibration and stabilization, improving the estimates of the robot orientation.
      Experiments in controlled underwater scenarios and in the sea have demonstrated a
      satisfactory performance and the capacity of the vehicle to operate in real
      environments and in real time. 

PMID- 25602262
TI  - Comprehensive feedback on trainee surgeons' non-technical skills.
AB  - OBJECTIVE: This study aimed to explore the content of conversations, feedback
      style, and perceived usefulness of feedback to trainee surgeons when
      conversations were stimulated by a tool for assessing surgeons' non-technical
      skills. METHODS: Trainee surgeons and their supervisors used the Non-Technical
      Skills for Surgeons in Denmark tool to stimulate feedback conversations. Audio
      recordings of post-operation feedback conversations were collected. Trainees and
      supervisors provided questionnaire responses on the usefulness and
      comprehensiveness of the feedback. The feedback conversations were qualitatively
      analyzed for content and feedback style. Usefulness was investigated using a
      scale from 1 to 5 and written comments were qualitatively analyzed. RESULTS: Six
      trainees and six supervisors participated in eight feedback conversations. Eighty
      questionnaires (response rate 83 percent) were collected from 13 trainees and 12
      supervisors. Conversations lasted median eight (2-15) minutes. Supervisors used
      the elements and categories in the tool to structure the content of the
      conversations. Supervisors tended to talk about the trainees' actions and their
      own frames rather than attempting to understand the trainees' perceptions.
      Supervisors and trainees welcomed the feedback opportunity and agreed that the
      conversations were useful and comprehensive. CONCLUSIONS: The content of the
      feedback conversations reflected the contents of the tool and the feedback was
      considered useful and comprehensive. However, supervisors talked primarily about
      their own frames, so in order for the feedback to reach its full potential,
      supervisors may benefit from training techniques to stimulate a deeper reflection
      among trainees.

PMID- 25602264
TI  - Resource-efficient fusion over fading and non-fading reporting channels for
      cooperative spectrum sensing.
AB  - Recently, a novel resource-efficient technique for the reporting channel
      transmissions in cooperative spectrum sensing was proposed. In this technique,
      secondary users are allowed to simultaneously send their local decisions to the
      fusion center, saving time and frequency resources. Expressions for the
      probabilities of detection and false alarm for the unitary-gain AWGN reporting
      channels were derived, while simulation results were given for both the AWGN and
      Rayleigh fading channels. Here, we provide an expression that is applicable to
      AWGN channels with different real-valued gains and to time-varying real-valued
      gains. A simple suboptimum receiver is proposed for the general complex-valued
      fading and non-fading channels, with an improved performance in the low signal-to
      noise ratio condition. Numerical results are shown for both the AWGN and Rayleigh
      fading reporting channels, demonstrating the accuracy of the derived expressions
      and the attractive performance of the proposed receiver. 

PMID- 25602265
TI  - Development of fabric-based chemical gas sensors for use as wearable electronic
      noses.
AB  - Novel gas sensors embroidered into fabric substrates based on polymers/ SWNT-COOH
      nanocomposites were proposed in this paper, aiming for their use as a wearable
      electronic nose (e-nose). The fabric-based chemical gas sensors were fabricated
      by two main processes: drop coating and embroidery. Four potential polymers (PVC,
      cumene-PSMA, PSE and PVP)/functionalized-SWCNT sensing materials were deposited
      onto interdigitated electrodes previously prepared by embroidering conductive
      thread on a fabric substrate to make an optimal set of sensors. After preliminary
      trials of the obtained sensors, it was found that the sensors yielded a
      electrical resistance in the region of a few kilo-Ohms. The sensors were tested
      with various volatile compounds such as ammonium hydroxide, ethanol, pyridine,
      triethylamine, methanol and acetone, which are commonly found in the wastes
      released from the human body. These sensors were used to detect and discriminate
      between the body odors of different regions and exist in various forms such as
      the urine, armpit and exhaled breath odor. Based on a simple pattern recognition
      technique, we have shown that the proposed fabric-based chemical gas sensors can
      discriminate the human body odor from two persons. 

PMID- 25602266
TI  - A cognitively-motivated framework for partial face recognition in unconstrained
      scenarios.
AB  - Humans perform and rely on face recognition routinely and effortlessly throughout
      their daily lives. Multiple works in recent years have sought to replicate this
      process in a robust and automatic way. However, it is known that the performance
      of face recognition algorithms is severely compromised in non-ideal image
      acquisition scenarios. In an attempt to deal with conditions, such as occlusion
      and heterogeneous illumination, we propose a new approach motivated by the global
      precedent hypothesis of the human brain's cognitive mechanisms of perception. An
      automatic modeling of SIFT keypoint descriptors using a Gaussian mixture model
      (GMM)-based universal background model method is proposed. A decision is, then,
      made in an innovative hierarchical sense, with holistic information gaining
      precedence over a more detailed local analysis. The algorithm was tested on the
      ORL, ARand Extended Yale B Face databases and presented state-of-the-art
      performance for a variety of experimental setups. 

PMID- 25602267
TI  - Improvement of the trapezoid method using raw landsat image digital count data
      for soil moisture estimation in the Texas (USA) high plains.
AB  - Variations in soil moisture strongly affect surface energy balances, regional
      runoff, land erosion and vegetation productivity (i.e., potential crop yield).
      Hence, the estimation of soil moisture is very valuable in the social, economic,
      humanitarian (food security) and environmental segments of society. Extensive
      efforts to exploit the potential of remotely sensed observations to help quantify
      this complex variable are ongoing. This study aims at developing a new index, the
      Thermal Ground cover Moisture Index (TGMI), for estimating soil moisture content.
      This index is based on empirical parameterization of the relationship between raw
      image digital count (DC) data in the thermal infrared spectral band and ground
      cover (determined from raw image digital count data in the red and near-infrared
      spectral bands).The index uses satellite-derived information only, and the
      potential for its operational application is therefore great. This study was
      conducted in 18 commercial agricultural fields near Lubbock, TX (USA). Soil
      moisture was measured in these fields over two years and statistically compared
      to corresponding values of TGMI determined from Landsat image data. Results
      indicate statistically significant correlations between TGMI and field
      measurements of soil moisture (R2 = 0.73, RMSE = 0.05, MBE = 0.17 and AAE =
      0.049), suggesting that soil moisture can be estimated using this index. It was
      further demonstrated that maps of TGMI developed from Landsat imagery could be
      constructed to show the relative spatial distribution of soil moisture across a
      region. 

PMID- 25602268
TI  - Fluorescent cellular assay for screening agents inhibiting Pseudomonas aeruginosa
      adherence.
AB  - Antibodies against Pseudomonas aeruginosa (PA) lectin, PAIIL, which is a
      virulence factor mediating the bacteria binding to epithelium cells, were
      prepared in chickens and purified from egg yolks. To examine these antibodies as
      a prophylactic agent preventing the adhesion of PA we developed a well plate
      assay based on fluorescently labeled bacteria and immortalized epithelium cell
      lines derived from normal and cystic fibrosis (CF) human lungs. The antibodies
      significantly inhibited bacteria adhesion (up to 50%) in both cell lines. In
      agreement with in vivo data, our plate assay showed higher susceptibility of CF
      cells towards the PA adhesion as compared to normal epithelium. This finding
      proved the reliability of the developed experimental system. 

PMID- 25602269
TI  - A novel vibration mode testing method for cylindrical resonators based on
      microphones.
AB  - Non-contact testing is an important method for the study of the vibrating
      characteristic of cylindrical resonators. For the vibratory cylinder gyroscope
      excited by piezo-electric electrodes, mode testing of the cylindrical resonator
      is difficult. In this paper, a novel vibration testing method for cylindrical
      resonators is proposed. This method uses a MEMS microphone, which has the
      characteristics of small size and accurate directivity, to measure the vibration
      of the cylindrical resonator. A testing system was established, then the system
      was used to measure the vibration mode of the resonator. The experimental results
      show that the orientation resolution of the node of the vibration mode is better
      than 0.1 degrees . This method also has the advantages of low cost and easy
      operation. It can be used in vibration testing and provide accurate results,
      which is important for the study of the vibration mode and thermal stability of
      vibratory cylindrical gyroscopes. 

PMID- 25602270
TI  - A novel joint spatial-code clustered interference alignment scheme for large
      scale wireless sensor networks.
AB  - Interference alignment (IA) has been put forward as a promising technique which
      can mitigate interference and effectively increase the throughput of wireless
      sensor networks (WSNs). However, the number of users is strictly restricted by
      the IA feasibility condition, and the interference leakage will become so strong
      that the quality of service will degrade significantly when there are more users
      than that IA can support. In this paper, a novel joint spatial-code clustered
      (JSCC)-IA scheme is proposed to solve this problem. In the proposed scheme, the
      users are clustered into several groups so that feasible IA can be achieved
      within each group. In addition, each group is assigned a pseudo noise (PN) code
      in order to suppress the inter-group interference via the code dimension. The
      analytical bit error rate (BER) expressions of the proposed JSCC-IA scheme are
      formulated for the systems with identical and different propagation delays,
      respectively. To further improve the performance of the JSCC-IA scheme in
      asymmetric networks, a random grouping selection (RGS) algorithm is developed to
      search for better grouping combinations. Numerical results demonstrate that the
      proposed JSCC-IA scheme is capable of accommodating many more users to
      communicate simultaneously in the same frequency band with better performance. 

PMID- 25602271
TI  - Design and Fabrication of Interdigital Nanocapacitors Coated with HfO2.
AB  - In this article nickel interdigital capacitors were fabricated on top of silicon
      substrates. The capacitance of the interdigital capacitor was optimized by
      coating the electrodes with a 60 nm layer of HfO2. An analytical solution of the
      capacitance was compared to electromagnetic simulations using COMSOL and with
      experimental measurements. Results show that modeling interdigital capacitors
      using Finite Element Method software such as COMSOL is effective in the design
      and electrical characterization of these transducers. 

PMID- 25602272
TI  - Design and testing of an agricultural implement for underground application of
      rodenticide bait.
AB  - An agricultural implement for underground application of rodenticide bait to
      control the Mediterranean pocket gopher (Microtus Duodecimcostatus) in fruit
      orchards has been designed and tested. The main objective of this research was to
      design and test the implement by using the finite element method (FEM) and
      considering a range of loads generated on most commonly used furrow openers in
      agricultural implements. As a second step, the prototype was tested in the field
      by analysing the effects of forward speed and application depth on the mechanical
      behaviour of the implement structure. The FEM was used in the design phase and a
      prototype was manufactured. The structural strains on the prototype chassis under
      working conditions were tested by using strain gauges to validate the design
      phase. Three forward speeds (4.5, 5.5, and 7.0 km/h), three application depths
      (0.12, 0.15, and 0.17 m), and two types of soil (clayey-silty-loam and clayey
      silty-sandy) were considered. The prototype was validated successfully by
      analysing the information obtained from the strain gauges. The Von Mises stresses
      indicated a safety coefficient of 1.9 for the most critical load case. Although
      both forward speed and application depth had a significant effect on the stresses
      generated on the chassis, the latter parameter critically affected the structural
      behaviour of the implement. The effects of the application depth on the strains
      were linear such that strains increased with depth. In contrast, strains remained
      roughly constant regardless of variation in the forward speed. 

PMID- 25602273
TI  - Leisure engagement and subjective well-being: A meta-analysis.
AB  - Numerous studies show a link between leisure engagement and subjective well-being
      (SWB). Drawing on common experiential features of leisure, psychological need
      theories, and bottom-up models of SWB, we suggest that leisure engagement
      influences SWB via leisure satisfaction. We examine the proposed cross-sectional
      relations and mediation model using random-effects meta-analyses that include all
      available populations. To provide a stronger test of causal influence, we also
      examine longitudinal relations between leisure satisfaction and SWB and effects
      of experimental leisure interventions on SWB using random effects meta-analyses
      of all available populations. Findings based on 37 effect sizes and 11,834
      individuals reveal that leisure engagement and SWB are moderately associated
      (inverse-variance weighted r = .26) and mediated by leisure satisfaction. Cross
      lagged regression analyses of longitudinal studies, controlling for prior SWB,
      reveal bottom-up effects of leisure satisfaction on SWB (beta = .15) and top-down
      effects of SWB on leisure satisfaction (beta = .16). Experimental studies reveal
      that leisure interventions enhance SWB (d = 1.02). Compared with working samples,
      retired samples exhibit a stronger relation between leisure engagement and SWB,
      and between leisure satisfaction and SWB. Measures of the frequency and diversity
      of leisure engagement are more strongly associated with SWB than measures of time
      spent in leisure. Overall, although not minimizing top-down influences, results
      are consistent with bottom-up models of SWB and suggest that the leisure domain
      is a potentially important target for enhancing SWB.

PMID- 25602274
TI  - Synthetic study toward the misassigned (+/-)-tronoharine.
AB  - The synthesis of a pentacyclic indole compound corresponding to the core
      structure of the misassigned indole alkaloid, tronoharine (1), is presented. The
      key reactions were a formal [3 + 3] cycloaddition of an indol-2-yl carbinol with
      an azadiene for the construction of the 6/5/6/6 tetracyclic system containing an
      all-carbon quaternary center and an intramolecular substitution reaction of an
      amine and a triflate for the creation of the bridged azepine ring. In addition,
      some other interesting transformations discovered during the synthetic studies
      are also discussed. 

PMID- 25602275
TI  - The meaning and measurement of work fatigue: Development and evaluation of the
      Three-Dimensional Work Fatigue Inventory (3D-WFI).
AB  - Although work fatigue represents an important construct in several substantive
      areas, prior conceptual definitions and measures have been inadequate in a number
      of ways. The goals of the present study were to develop a conceptual definition
      and outline the desirable characteristics of a work fatigue measure, briefly
      examine several prior measures of work fatigue-related constructs, and develop
      and evaluate a new measure of work fatigue. The Three-Dimensional Work Fatigue
      Inventory (3D-WFI) provides separate and commensurate assessments of physical,
      mental, and emotional work fatigue. Results from a pilot study (n = 207) and a
      broader evaluative study of U.S. wage and salary workers (n = 2,477) suggest that
      the 3D-WFI is psychometrically sound and evinces a meaningful pattern of
      relations with variables that comprise the nomological network of work fatigue.
      As with all new measures, additional research is required to evaluate fully the
      utility of the 3D-WFI in research on work fatigue.

PMID- 25602276
TI  - On the front lines: Stakeholder threat cues determine how identified employees
      cope with scandal.
AB  - When organizational identity is threatened as a result of scandal, highly
      identified members who represent the threatened organization to stakeholders have
      a particularly challenging and overlooked experience. Addressing a theoretical
      paradox, we propose that organizational identification interacts with the threat
      cues from stakeholders to determine employee responses. We conducted a
      multimethod, in vivo test of these ideas with university fundraising employees
      after events threatened the university's moral identity. Interview and archival
      data demonstrated that stakeholders expressed identity threat to fundraisers, who
      experienced their own identity-related distress and engaged in both group
      dissociative and group-affirming responses. Surveys of professional and student
      university fundraisers demonstrated that more identified employees were more
      distressed (e,g., felt anxious, grief, betrayed) regardless of stakeholder threat
      cues. Yet, when employees perceived weak threat cues from stakeholders, more
      identified members were less likely to dissociate from the group and more likely
      to affirm the group's positive identity with stakeholders. These benefits of
      identification were not present when the stakeholder threat cues were strong. We
      discuss future research and practical implications of front-line employee
      identification and stakeholder cues during scandal.

PMID- 25602277
TI  - When confidence comes and goes: How variation in self-efficacy moderates stressor
      strain relationships.
AB  - Inconsistent published findings regarding a proposed buffering role of self
      efficacy in stress coping led us to develop a model in which within-person
      variability in self-efficacy over time affects how individuals' mean levels of
      self-efficacy moderate the relationship between demands and psychological
      symptoms. Results from two independent samples (manufacturing workers and college
      students) supported the hypothesized interaction between demands, self-efficacy
      mean level, and self-efficacy variability. Demands were more positively
      associated with psychological strain among those with high and stable self
      efficacy than those with high and variable self-efficacy. We discuss the
      implications of intrapersonal variability in self-efficacy for research on stress
      coping.

PMID- 25602278
TI  - Spillover of interpersonal conflicts from work into nonwork: A daily diary study.
AB  - [Correction Notice: An Erratum for this article was reported in Vol 20(3) of
      Journal of Occupational Health Psychology (see record 2015-15847-001). There was
      a misspelling in the figures. The legends for Figure 1 and Figure 2 should read
      "High Daily Resilience".] This study among a heterogeneous sample of employees
      expands the Job-Demands (JD-R) theory by examining how interpersonal conflicts at
      work-task and relationship conflict-spillover into the nonwork domain on a daily
      basis. We hypothesized that daily personal resources can buffer the daily
      negative spillover of interpersonal conflicts from work into the nonwork domain.
      A total of 113 employees (n = 565 occasions) filled in a daily diary
      questionnaire in the evening before bedtime over 5 consecutive working days.
      Results of multilevel analysis showed that the presence of daily personal
      resources is essential to buffer the spillover of interpersonal conflict at work
      to the nonwork domain. Specifically, on days that employees were not very
      optimistic or resilient, interpersonal conflicts resulted in higher strain-based
      work-life conflict experiences. These findings contribute to the JD-R theory and
      show how the unfavorable effects of daily interpersonal conflicts in the work
      domain may be avoided in the nonwork domain through enhancing personal resources.
      We discuss the implications for theory and practice. (PsycINFO Database Record 

PMID- 25602279
TI  - Killing mechanism of stable N-halamine cross-linked polymethacrylamide
      nanoparticles that selectively target bacteria.
AB  - Increased resistance of bacteria to disinfection and antimicrobial treatment
      poses a serious public health threat worldwide. This has prompted the search for
      agents that can inhibit both bacterial growth and withstand harsh conditions
      (e.g., high organic loads). In the current study, N-halamine-derivatized cross
      linked polymethacrylamide nanoparticles (NPs) were synthesized by
      copolymerization of the monomer methacrylamide (MAA) and the cross-linker monomer
      N,N-methylenebis(acrylamide) (MBAA) and were subsequently loaded with oxidative
      chlorine using sodium hypochlorite (NaOCl). The chlorinated NPs demonstrated
      remarkable stability and durability to organic reagents and to repetitive
      bacterial loading cycles as compared with the common disinfectant NaOCl (bleach),
      which was extremely labile under these conditions. The antibacterial mechanism of
      the cross-linked P(MAA-MBAA)-Cl NPs was found to involve generation of reactive
      oxygen species (ROS) only upon exposure to organic media. Importantly, ROS were
      not generated upon suspension in water, revealing that the mode of action is
      target-specific. Further, a unique and specific interaction of the chlorinated
      NPs with Staphylococcus aureus was discovered, whereby these microorganisms were
      all specifically targeted and marked for destruction. This bacterial encircling
      was achieved without using a targeting module (e.g., an antibody or a ligand) and
      represents a highly beneficial, natural property of the P(MAA-MBAA)-Cl
      nanostructures. Our findings provide insights into the mechanism of action of
      P(MAA-MBAA)-Cl NPs and demonstrate the superior efficacy of the NPs over bleach
      (i.e., stability, specificity, and targeting). This work underscores the
      potential of developing sustainable P(MAA-MBAA)-Cl NP-based devices for
      inhibiting bacterial colonization and growth. 

PMID- 25602281
TI  - Knowledge and uses of African pangolins as a source of traditional medicine in
      Ghana.
AB  - Traditional medicine has been practised in Ghana for centuries with the majority
      of Ghanaians still patronising the services of traditional healers. Throughout
      Africa a large number of people use pangolins as a source of traditional
      medicine, however, there is a dearth of information on the use of animals in folk
      medicine in Ghana, in particular the use of pangolins. The aim of this study was
      to determine the prevalent use of pangolins and the level of knowledge of
      pangolin use among traditional healers in Ghana for the treatment of human
      ailments. Data was gathered from 48 traditional healers using semi-structured
      interviews on the traditional medicinal use of pangolin body parts in the Kumasi
      metropolis of Ghana. The cultural importance index, relative frequency of
      citation, informant agreement ratio and use agreement values were calculated to
      ascertain the most culturally important pangolin body part as well as the level
      of knowledge dissemination among traditional healers with regards pangolin body
      parts. Our study revealed that 13 body parts of pangolins are used to treat
      various medicinal ailments. Pangolin scales and bones were the most prevalent
      prescribed body parts and indicated the highest cultural significance among
      traditional healing practices primarily for the treatment of spiritual
      protection, rheumatism, financial rituals and convulsions. Despite being
      classified under Schedule 1 of Ghana's Wildlife Conservation Act of 1971 (LI
      685), that prohibits anyone from hunting or being in possession of a pangolin,
      our results indicated that the use of pangolins for traditional medicinal
      purposes is widespread among traditional healers in Ghana. A study on the
      population status and ecology of the three species of African pangolins occurring
      in Ghana is urgently required in order to determine the impact this harvest for
      traditional medical purposes has on their respective populations as current
      levels appear to be unmonitored and unsustainable. 

PMID- 25602283
TI  - Where next for microbiome research?
AB  - The development of high-throughput sequencing technologies has transformed our
      capacity to investigate the composition and dynamics of the microbial communities
      that populate diverse habitats. Over the past decade, these advances have yielded
      an avalanche of metagenomic data. The current stage of "van Leeuwenhoek"-like
      cataloguing, as well as functional analyses, will likely accelerate as DNA and
      RNA sequencing, plus protein and metabolic profiling capacities and computational
      tools, continue to improve. However, it is time to consider: what's next for
      microbiome research? The short pieces included here briefly consider the
      challenges and opportunities awaiting microbiome research. 

PMID- 25602282
TI  - Evaluation of the DNA barcodes in Dendrobium (Orchidaceae) from mainland Asia.
AB  - DNA barcoding has been proposed to be one of the most promising tools for
      accurate and rapid identification of taxa. However, few publications have
      evaluated the efficiency of DNA barcoding for the large genera of flowering
      plants. Dendrobium, one of the largest genera of flowering plants, contains many
      species that are important in horticulture, medicine and biodiversity
      conservation. Besides, Dendrobium is a notoriously difficult group to identify.
      DNA barcoding was expected to be a supplementary means for species
      identification, conservation and future studies in Dendrobium. We assessed the
      power of 11 candidate barcodes on the basis of 1,698 accessions of 184 Dendrobium
      species obtained primarily from mainland Asia. Our results indicated that five
      single barcodes, i.e., ITS, ITS2, matK, rbcL and trnH-psbA, can be easily
      amplified and sequenced with the currently established primers. Four barcodes,
      ITS, ITS2, ITS+matK, and ITS2+matK, have distinct barcoding gaps. ITS+matK was
      the optimal barcode based on all evaluation methods. Furthermore, the efficiency
      of ITS+matK was verified in four other large genera including Ficus, Lysimachia,
      Paphiopedilum, and Pedicularis in this study. Therefore, we tentatively recommend
      the combination of ITS+matK as a core DNA barcode for large flowering plant
      genera. 

PMID- 25602285
TI  - Magic-size II-VI nanoclusters as synthons for flat colloidal nanocrystals.
AB  - Five new, discretely sized, magic-size II-VI nanoclusters are synthesized in
      primary-amine bilayer templates and are isolated as the derivatives [(CdS)(34)(n
      butylamine)(18)], [(ZnS)(34)(n-butylamine)(34)], [(ZnSe)(13)(n-butylamine)(13)],
      [(CdTe)(13)(n-propylamine)(13)], and [(ZnTe)(13)(n-butylamine)(13)]. The
      nanoclusters are characterized by elemental analysis, UV-visible absorption
      spectroscopy, laser-desorption-ionization mass spectrometry, and transmission
      electron microscopy. Four of the nanocluster precursors are converted to
      wurtzitic CdS, ZnS, and ZnSe quantum platelets and CdTe quantum belts,
      respectively, under mild conditions.

PMID- 25602284
TI  - Proportions of Staphylococcus aureus and methicillin-resistant Staphylococcus
      aureus in patients with surgical site infections in mainland China: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Sufficient details have not been specified for the epidemiological
      characteristics of Staphylococcus aureus (S. aureus) and methicillin-resistant
      Staphylococcus aureus (MRSA) among surgical site infections (SSIs) in mainland
      China. This systematic review aimed to estimate proportions of S. aureus and MRSA
      in SSIs through available published studies. METHODS: PubMed, Embase and four
      Chinese electronic databases were searched to identify relevant primary studies
      published between 2007 and 2012. Meta-analysis was conducted on the basis of
      logit-transformed metric for proportions of S. aureus and MRSA, followed by pre
      defined subgroup meta-analysis. Random-effects meta-regression was also conducted
      to explore the impact of possible factors on S. aureus proportions. RESULTS: 106
      studies were included, of which 38 studies involved MRSA. S. aureus accounted for
      19.1% (95%CI 17.2-21.0%; I(2) = 84.1%) of all isolates in SSIs, which was roughly
      parallel to 18.5% in the United States (US) (P-value = 0.57) but significantly
      exceeded those calculated through the surveillance system in China (P
      value<0.001). In subgroup analysis, S. aureus in patients with thoracic surgery
      (41.1%, 95%CI 26.3-57.7%; I(2) = 74.4%) was more common than in those with
      gynecologic surgery (20.1%, 95%CI 15.6-25.6%; I(2) = 33.0%) or abdominal surgery
      (13.8%, 95%CI 10.3-18.4%; I(2) = 70.0%). Similar results were found in meta
      regression. MRSA accounted for 41.3% (95%CI 36.5-46.3%; I(2) = 64.6%) of S.
      aureus, significantly lower than that in the US (P-value = 0.001). MRSA was
      sensitive to vancomycin (522/522) and linezolid (93/94), while 79.9% (95%CI 67.4
      88.4%; I(2) = 0%) and 92.0% (95%CI 80.2-97.0%; I(2) = 0%) of MRSA was resistant
      to clindamycin and erythromycin respectively. CONCLUSION: The overall proportion
      of S. aureus among SSIs in China was similar to that in the US but seemed higher
      than those reported through the Chinese national surveillance system. Proportions
      of S. aureus SSIs may vary with different surgery types. Commonly seen in SSIs,
      MRSA tended to be highly sensitive to vancomycin and linezolid but mostly
      resistant to clindamycin and erythromycin.

PMID- 25602287
TI  - A review of conventional and drug-eluting chemoembolization in the treatment of
      colorectal liver metastases: principles and proof.
AB  - The management of colorectal liver metastasis has undergone a significant change
      since the development of novel ablation and embolization. Drug-eluting
      microsphere platforms, designed to deliver targeted concentrations of systemic
      therapy directly into the tumor via its arterial vasculature, have garnered
      interest and gained in popularity in recent years. Based on in vitro and in vivo
      data, multiple factors contribute to locoregional exposure including carrier
      base, smaller particle size (larger surface area), chemotherapeutic and
      chemotherapeutic intensity. Based on the current published clinical data, therapy
      appears well tolerated but the questions remain as to the ideal technique,
      patient population and overall efficacy. The purpose of this article is to
      provide a perspective on the scientific basis, and clinical review of the current
      data supporting the use of this platform in the setting of metastatic colorectal
      carcinoma.

PMID- 25602288
TI  - Molecular orientational order probed by coherent anti-Stokes Raman scattering
      (CARS) and stimulated Raman scattering (SRS) microscopy: a spectral comparative
      study.
AB  - We investigate how to extract information on the orientational order of molecular
      bonds in biological samples from polarized coherent anti-Stokes Raman scattering
      (CARS) and stimulated Raman scattering (SRS) microscopy. Experimentally, the mean
      orientation of the molecular angular distribution, as well as its second and
      fourth orders of symmetry, are estimated by monitoring intensity signals under a
      varying incident polarization. We provide a generic method of analysis of
      polarized signals in both CARS and SRS contrasts, and apply it to imaging of
      lipid bonds' orientational order in multilamellar vesicles. A comparison of the
      two contrasts in the lipid region around 3000 cm(-1) shows that while SRS allows
      retrieving pure molecular order information, CARS is generally tainted by a bias
      from the nonresonant contribution. 

PMID- 25602289
TI  - Morphology and activity tuning of Cu3Pt/C ordered intermetallic nanoparticles by
      selective electrochemical dealloying.
AB  - Improving the catalytic activity of Pt-based bimetallic nanoparticles is a key
      challenge in the application of proton-exchange membrane fuel cells.
      Electrochemical dealloying represents a powerful approach for tuning the surface
      structure and morphology of these catalyst nanoparticles. We present a
      comprehensive study of using electrochemical dealloying methods to control the
      morphology of ordered Cu3Pt/C intermetallic nanoparticles, which could
      dramatically affect their electrocatalytic activity for the oxygen reduction
      reaction (ORR). Depending on the electrochemical dealloying conditions, the
      nanoparticles with Pt-rich core-shell or porous structures were formed. We
      further demonstrate that the core-shell and porous morphologies can be combined
      to achieve the highest ORR activity. This strategy provides new guidelines for
      optimizing nanoparticles synthesis and improving electrocatalytic activity. 

PMID- 25602286
TI  - Correlation of hypertension and proteinuria with outcome in elderly bevacizumab
      treated patients with metastatic colorectal cancer.
AB  - BACKGROUND: Studies suggest a relationship between hypertension and outcome in
      bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We
      performed a retrospective analysis of two phase II studies (BECA and BECOX) to
      determine if hypertension and proteinuria predict outcome in elderly patients
      with mCRC treated with bevacizumab. PATIENTS AND METHODS: Patients >= 70 years of
      age received either capecitabine 1250 mg/m(2) bid days 1-14 + bevacizumab 7.5
      mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m(2) bid days 1-14
      with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) day 1 (BECOX study). The
      primary objective was to correlate hypertension and proteinuria with overall
      response rate (ORR), time to progression (TTP) and overall survival (OS).
      Secondary objectives included identification of risk factors associated with the
      development of hypertension and proteinuria and determining whether development
      of hypertension or proteinuria in the first 2 cycles was related to ORR, disease
      control rate (DCR), TTP or OS. RESULTS: In total, 127 patients (median age 75.5
      years) were included in the study. Hypertension correlated with DCR and OS;
      proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first
      2 cycles did not correlate with efficacy. Risk factors for hypertension were
      female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR
      1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P =
      0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis
      identified as having prognostic value: baseline lactate dehydrogenase,
      haemoglobin, number of metastatic lesions and DCR. CONCLUSION: This analysis of
      two phase II studies suggests that hypertension is significantly correlated with
      OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not
      with OS and TTP. Both hypertension and proteinuria are associated with the
      duration of bevacizumab treatment and do not represent an independent prognostic
      factor.

PMID- 25602290
TI  - Helping Aged Victims of Crime (the HAVoC Study): Common Crime, Older People and
      Mental Illness.
AB  - BACKGOUND: Limited data suggest that crime may have a devastating impact on older
      people. Although identification and treatment may be beneficial, no well-designed
      studies have investigated the prevalence of mental disorder and the potential
      benefits of individual manualized CBT in older victims of crime. AIMS: To
      identify mental health problems in older victims of common crime, provide
      preliminary data on its prevalence, and conduct a feasibility randomized
      controlled trial (RCT) using mixed methods. METHOD: Older victims, identified
      through police teams, were screened for symptoms of anxiety, depression or post
      traumatic stress disorder (PTSD) one (n = 581) and 3 months (n = 486) after
      experiencing a crime. Screen positive participants were offered diagnostic
      interviews. Of these, 26 participants with DSM-IV diagnoses agreed to be
      randomized to Treatment As Usual (TAU) or TAU plus our manualized CBT informed
      Victim Improvement Package (VIP). The latter provided feedback on the VIP.
      RESULTS: Recruitment, assessment and intervention are feasible and acceptable. At
      3 months 120/486 screened as cases, 33 had DSM-IV criteria for a psychiatric
      disorder; 26 agreed to be randomized to a pilot trial. There were trends in
      favour of the VIP in all measures except PTSD at 6 months post crime.
      CONCLUSIONS: This feasibility RCT is the first step towards improving the lives
      of older victims of common crime. Without intervention, distress at 3 and 6
      months after a crime remains high. However, the well-received VIP appeared
      promising for depressive and anxiety symptoms, but possibly not posttraumatic
      stress disorder.

PMID- 25602291
TI  - Adherence to biologic therapies and associated factors in rheumatoid arthritis,
      spondyloarthritis and psoriatic arthritis: a systematic literature review.
AB  - OBJECTIVES: To analyse the evidence on adherence to biologic therapies in
      rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA).
      METHODS: Systematic review of studies retrieved by a sensitive search strategy in
      MEDLINE database (1961 through March 2012). To be selected, studies had to
      include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous
      biologic therapies, and had to report on measures of adherence. By design, only
      randomised controlled trials (RCT) or high quality cohort studies with a control
      group were selected. RESULTS: A total of 24 studies were included, of which 12
      reported results from national or local biologic registers, 9 were retrospective
      studies, 2 prospective studies, and only one was an RCT. Patients included were
      mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a
      great variability in the definition of adherence, measurement methods, and
      associated factors analysed. In general, adherence to etanercept was superior to
      that of other biologics, by the measures utilised. The main predictive factors -
      age, sex, comorbidity, baseline clinical condition, previous or concomitant use
      of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse,
      even divergent results across studies. CONCLUSIONS: There is a wide variability
      related to the adherence concept and its measurement, reflecting the complexity
      of the phenomenon. In order to draw more consistent conclusions about the
      relative value of predictive factors on adherence and persistence of biological
      therapy, larger controlled studies with better selection of variables and
      analysis of interactions are needed.

PMID- 25602292
TI  - Systematic drug repositioning for a wide range of diseases with integrative
      analyses of phenotypic and molecular data.
AB  - Drug repositioning, or the application of known drugs to new indications, is a
      challenging issue in pharmaceutical science. In this study, we developed a new
      computational method to predict unknown drug indications for systematic drug
      repositioning in a framework of supervised network inference. We defined a
      descriptor for each drug-disease pair based on the phenotypic features of drugs
      (e.g., medicinal effects and side effects) and various molecular features of
      diseases (e.g., disease-causing genes, diagnostic markers, disease-related
      pathways, and environmental factors) and constructed a statistical model to
      predict new drug-disease associations for a wide range of diseases in the
      International Classification of Diseases. Our results show that the proposed
      method outperforms previous methods in terms of accuracy and applicability, and
      its performance does not depend on drug chemical structure similarity. Finally,
      we performed a comprehensive prediction of a drug-disease association network
      consisting of 2349 drugs and 858 diseases and described biologically meaningful
      examples of newly predicted drug indications for several types of cancers and
      nonhereditary diseases. 

PMID- 25602293
TI  - The rise of two-dimensional materials.

PMID- 25602295
TI  - Abortive and propagating intracellular calcium waves: analysis from a hybrid
      model.
AB  - The functional properties of inositol(1,4,5)-triphosphate (IP3) receptors allow a
      variety of intracellular Ca(2+) phenomena. In this way, global phenomena, such as
      propagating and abortive Ca(2+) waves, as well as local events such as puffs,
      have been observed. Several experimental studies suggest that many features of
      global phenomena (e.g., frequency, amplitude, speed wave) depend on the interplay
      of biophysical processes such as diffusion, buffering, efflux and influx rates,
      which in turn depend on parameters such as buffer concentration, Ca(2+) pump
      density, cytosolic IP3 level, and intercluster distance. Besides, it is known
      that cells are able to modify some of these parameters in order to regulate the
      Ca(2+) signaling. By using a hybrid model, we analyzed different features of the
      hierarchy of calcium events as a function of two relevant parameters for the
      calcium signaling, the intercluster distance and the pump strength or intensity.
      In the space spanned by these two parameters, we found two modes of calcium
      dynamics, one dominated by abortive calcium waves and the other by propagating
      waves. Smaller distances between the release sites promote propagating calcium
      waves, while the increase of the efflux rate makes the transition from
      propagating to abortive waves occur at lower values of intercluster distance. We
      determined the frontier between these two modes, in the parameter space defined
      by the intercluster distance and the pump strength. Furthermore, we found that
      the velocity of simulated calcium waves accomplishes Luther's law, and that an
      effective rate constant for autocatalytic calcium production decays linearly with
      both the intercluster distance and the pump strength.

PMID- 25602294
TI  - Acute cutaneous wounds treated with human decellularised dermis show enhanced
      angiogenesis during healing.
AB  - BACKGROUND: The influence of skin substitutes upon angiogenesis during wound
      healing is unclear. OBJECTIVES: To compare the angiogenic response in acute
      cutaneous human wounds treated with autogenic, allogenic and xenogenic skin
      substitutes to those left to heal by secondary intention. METHODS: On day 0, four
      5mm full-thickness punch biopsies were harvested from fifty healthy volunteers
      (sites 1-4). In all cases, site 1 healed by secondary intention (control), site 2
      was treated with collagen-GAG scaffold (CG), cadaveric decellularised dermis
      (DCD) was applied to site 3, whilst excised tissue was re-inserted into site 4
      (autograft). Depending on study group allocation, healing tissue from sites 1-4
      was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used
      in histological and immunohistochemical evaluation whilst extracted RNA from the
      remainder enabled whole genome microarrays and qRT-PCR of highlighted
      angiogenesis-related genes. All wounds were serially imaged over 6 weeks using
      laser-doppler imaging and spectrophotometric intracutaneous analysis. RESULTS:
      Inherent structural differences between skin substitutes influenced the
      distribution and organisation of capillary networks within regenerating dermis.
      Haemoglobin flux (p = 0.0035), oxyhaemoglobin concentration (p = 0.0005), and
      vessel number derived from CD31-based immunohistochemistry (p = 0.046) were
      significantly greater in DCD wounds at later time points. This correlated with
      time-matched increases in mRNA expression of membrane-type 6 matrix
      metalloproteinase (MT6-MMP) (p = 0.021) and prokineticin 2 (PROK2) (p = 0.004).
      CONCLUSION: Corroborating evidence from invasive and non-invasive modalities
      demonstrated that treatment with DCD resulted in increased angiogenesis after
      wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and
      extracellular matrix protease MT6-MMP seen only in the DCD group may contribute
      to observed responses.

PMID- 25602296
TI  - An unusual cause of right heart failure.

PMID- 25602298
TI  - Cumulative analysis on 4802 patients confirming that women benefit more than men
      from cardiac resynchronization therapy.

PMID- 25602299
TI  - Clarithromycin for stable coronary heart disease increases all-cause and
      cardiovascular mortality and cerebrovascular morbidity over 10years in the
      CLARICOR randomised, blinded clinical trial.
AB  - BACKGROUND: The CLARICOR trial reported that clarithromycin compared with placebo
      increased all-cause mortality in patients with stable coronary heart disease.
      This study investigates the effects of clarithromycin versus placebo during
      10years follow up. METHODS: The CLARICOR trial is a randomised, placebo
      controlled trial including 4373 patients with stable coronary heart disease. The
      interventions were 2weeks of clarithromycin 500mg a day versus placebo. 10year
      follow up was performed through Danish public registers and analysed with Cox
      regression. RESULTS: Clarithromycin increased all-cause mortality (hazard ratio
      (HR): 1.10, 95% confidence interval (CI): 1.00-1.21) and cerebrovascular disease
      during 10years (HR: 1.19, 95% CI: 1.02-1.38). The increased mortality and
      morbidity were restricted to patients not on statin at entry (HR: 1.16, 95% CI:
      1.04-1.31, and HR: 1.25, 95% CI: 1.03-1.50). The assumption of constant HR during
      the 10years was violated for cardiovascular death (P=0.01) and cardiovascular
      death outside hospital (P<0.0005). Analyses of the effects over time showed that
      clarithromycin increased cardiovascular mortality during the first three years
      (HR: 1.42, 95% CI: 1.09-1.84) due to increased cardiovascular mortality outside
      hospital in patients not on statin (HR: 2.36, 95% CI: 1.60-3.50). During the last
      4years, cardiovascular death outside hospital was lower in the clarithromycin
      group (HR: 0.64, 95% CI: 0.46-0.88). CONCLUSION: Clarithromycin increased
      mortality due to cardiovascular death outside hospital and cerebrovascular
      morbidity in patients with stable coronary heart disease who were not on statin.
      The increased cardiovascular mortality was years later compensated, likely
      through frailty attrition.

PMID- 25602300
TI  - Evaluation of age-dependent response to NMDA receptor antagonism in zebrafish.
AB  - Imbalances in glutamatergic signaling have been proposed as the cause of several
      neurological disturbances. The use of MK-801, an N-methyl-D-aspartate (NMDA)
      receptor antagonist, to mimic features of these neurological disorders is
      effective both in mammals and in fish. However, the variability of the subunits
      comprising the NMDA receptor during development alters the pharmacokinetic
      properties of the receptor and leads to different responses to this drug. Here,
      we evaluated the locomotor response of zebrafish to MK-801 (1, 5, and 20 MUM)
      through the development (30 days postfertilization [dpf] to 2 years
      postfertilization [ypf]). The NMDA receptor subunit gene expression was also
      analyzed through the development (7 dpf to 2 ypf). Zebrafish displayed an age
      related response to MK-801 with a higher response at 60 and 120 dpf. The
      magnitude of hyperlocomotion promoted by MK-801 seems to be less powerful for
      zebrafish in relation to rodents. The verification of expression levels in
      zebrafish NMDA receptor subunits shows that NR1.1 had a slight reduction
      throughout the development, while the NR2 subunits, especially NR2A.2 and NR2C.1,
      vary their expression levels according to the stage of development. The time
      specific locomotor response to MK-801 through the development could be a
      consequence of differential NMDA receptor subunit expression. This result of
      developmental response to MK-801 is a crucial component in the consolidation of
      zebrafish as a suitable model to study glutamatergic neurotransmission in early
      phases.

PMID- 25602301
TI  - Deimatic displays.

PMID- 25602297
TI  - Utility of the SENIORS elderly heart failure risk model applied to the RICA
      registry of acute heart failure.
AB  - BACKGROUND: Heart failure (HF) is predominantly a disease of the elderly.
      Reliable risk stratification would help in the management of this population, but
      no model has been well evaluated in elderly HF patients in both acute and chronic
      settings and not being restricted by ejection fraction. To evaluate the utility
      of the SENIORS risk model, developed from a clinical trial of elderly patients
      with chronic HF, in an independent cohort (National Spanish Registry: RICA) of
      elderly acute HF patients. METHODS: We applied the SENIORS risk model to 926
      patients in RICA to estimate risk at one year of a) composite outcome of all
      cause mortality or cardiovascular hospital admission and b) all-cause mortality.
      RESULTS: In the RICA registry mean age was 78years, mean ejection fraction 51%
      and 87% were in NYHA II and III. At one year death/CV hospitalization occurred in
      31.9% and all-cause mortality in 19.5%. The risk model provided good separation
      of Kaplan Meier curves stratified by tertile for death/CV hospitalization and all
      cause mortality. The observed versus expected rates of death/CV hospitalization
      in the lowest, middle and highest risk tertiles were (%) 34/24, 45/41 and 57/67,
      and for death 13/16, 32/38 and 44/70 respectively. C-statistic for all-cause
      mortality or CV hospitalization was 0.60 and for all-cause mortality 0.66.
      CONCLUSION: The SENIORS risk model was a reliable tool for relative risk
      stratification among acute heart failure patients in a "real world" registry, but
      predicted versus observed risk showed some variability. The model provides a
      useful basis for clinical risk prediction.

PMID- 25602302
TI  - Visual rhythm perception improves through auditory but not visual training.

PMID- 25602303
TI  - Evolution: they never come back, or do they?
AB  - There is a notion in evolution that traits, once lost, cannot re-evolve. A new
      species of bone-eating worm defies this notion. Its males are free-living and
      look nothing like the dwarfed bags of sperm of its relatives. 

PMID- 25602304
TI  - Animal cognition: monkeys pass the mirror test.
AB  - A new study finds that rhesus monkeys display self-recognition behaviors toward a
      mirror after multimodal sensory-motor training. This finding closes a prior gap
      in the evolutionary continuity of animal cognition and opens new frontiers for
      exploring the neurobiological basis of self-awareness. 

PMID- 25602305
TI  - Membrane trafficking: licensing a cargo receptor for ER export.
AB  - Quality control in the endoplasmic reticulum prevents packaging of immature and
      misfolded proteins into vesicles, but the actual mechanisms involved in this
      process have not been defined for most cargos. A recent study demonstrates that
      the engagement of mature cargo with its receptor triggers the recruitment of a
      vesicle cargo adaptor. 

PMID- 25602306
TI  - Corvid cognition: something to crow about?
AB  - New research indicates that crows are capable of matching stimuli on the basis of
      analogical relations: that is, similarity of size, color and shape. This may be
      the first evidence for spontaneous analogical reasoning outside of the primate
      order. 

PMID- 25602307
TI  - Stress signaling: serotonin spreads systemic stress.
AB  - Cells respond to elevated temperatures through a well-characterized heat-shock
      response that enables short-term survival, long-term adaptation and mitigation of
      macromolecular damage. New work reveals a cell non-autonomous layer of stress
      response regulation between neurons and the gonad involving serotonin. 

PMID- 25602308
TI  - Mechanotransduction: feeling the squeeze in the C. elegans reproductive system.
AB  - A new study reports that the RhoGAP SPV-1 senses membrane curvature and cell
      stretch in the Caenorhabditis elegans spermatheca. Without SPV-1, the cells of
      the spermatheca are hypercontractile, leading to deformation and rapid ejection
      of the fertilized eggs. The spermatheca may provide a paradigm for understanding
      how cells detect mechanical stimuli in vivo.

PMID- 25602309
TI  - Multisensory integration: how sound alters sight.
AB  - What we hear can rapidly alter what we see. A new study provides evidence for a
      mechanism in which 10 Hz oscillations in the visual system define the time window
      for integrating auditory and visual information.

PMID- 25602310
TI  - Mitochondrial biogenesis: cell-cycle-dependent investment in making mitochondria.
AB  - Mitochondria cannot be made de novo, so pre-existing mitochondria must be
      inherited at each cell division. A new study demonstrates cell-cycle-dependent
      regulation of the activity of the TOM translocase complex to induce mitochondrial
      biogenesis during the M phase of the cell cycle. 

PMID- 25602311
TI  - Zebrafish stripes as a model for vertebrate colour pattern formation.
AB  - Colour patterns are prominent features of many animals and have important
      functions in communication, such as camouflage, kin recognition and mate choice.
      As targets for natural as well as sexual selection, they are of high evolutionary
      significance. The molecular mechanisms underlying colour pattern formation in
      vertebrates are not well understood. Progress in transgenic tools, in vivo
      imaging and the availability of a large collection of mutants make the zebrafish
      (Danio rerio) an attractive model to study vertebrate colouration. Zebrafish
      display golden and blue horizontal stripes that form during metamorphosis as
      mosaics of yellow xanthophores, silvery or blue iridophores and black
      melanophores in the hypodermis. Lineage tracing revealed the origin of the adult
      pigment cells and their individual cellular behaviours during the formation of
      the striped pattern. Mutant analysis indicated that interactions between all
      three pigment cell types are required for the formation of the pattern, and a
      number of cell surface molecules and signalling systems have been identified as
      mediators of these interactions. The understanding of the mechanisms that
      underlie colour pattern formation is an important step towards deciphering the
      genetic basis of variation in evolution.

PMID- 25602312
TI  - Quality of life in patients with benign nontoxic goiter: impact of disease and
      treatment response, and comparison with the general population.
AB  - BACKGROUND: While health-related quality of life (HRQoL) issues often prompt
      treatment of benign nontoxic goiter (NTG), few clinical studies have
      systematically assessed HRQoL in patients with this condition. The purpose of the
      present study was to evaluate thyroid-related and generic HRQoL in patients with
      benign NTG, as compared to the general population, before and six months after
      treatment. METHODS: Thyroid-related and generic HRQoL were assessed with Thyroid
      Patient-Reported Outcome (ThyPRO) and Medical Outcomes Study 36-item Short Form
      (SF-36), respectively. Baseline and six-month post-treatment HRQoL assessments
      were obtained from 111 patients with NTG who underwent radioiodine therapy (32%),
      hemithyroidectomy (53%), total thyroidectomy (12%), or cyst aspiration with
      ethanol sclerotherapy (4%). Euthyroid patients were enrolled at baseline, 80% of
      whom remained euthyroid six months post-treatment, with 20% experiencing
      subclinical thyroid dysfunction. Normative ThyPRO (n=739) and SF-36 (n=6638) data
      were collected from representative general population samples. Score differences
      between patients and the general population were analyzed with multivariate
      linear regression analysis, adjusting for age, sex, comorbidity, and educational
      status. Changes in scores between baseline and follow-up were analyzed with the
      paired t-test, and magnitudes of score changes were evaluated as effect sizes
      (mean difference/SDbaseline; 0.2-0.5 indicating small, 0.5-0.8 moderate, and >0.8
      large effects). RESULTS: Patients' baseline scores were significantly worse than
      those in the general population on 9 of the 13 ThyPRO scales. Six months after
      treatment, the patients' ThyPRO scores had improved on six scales, with
      large/moderate effects on the Goiter Symptoms and Anxiety scales. However, on
      eight scales, the post-treatment patient scores were still significantly worse
      than the general population scores. At baseline, patients had worse scores than
      the general population on four of the eight SF-36 scales and the SF-36 Mental
      Component Summary, none of which improved after treatment. CONCLUSIONS: Compared
      with the general population, patients with NTG had greatest HRQoL impairment at
      baseline on the Goiter Symptoms and Anxiety scales, which also demonstrated the
      largest post-treatment improvements. However, both disease-specific and generic
      HRQoL deficits persisted six months after treatment. In order to improve
      individualized care, future studies should focus on identifying risk factors for
      persistent HRQoL deficits and compare HRQoL effects of the various goiter
      treatment modalities in relation to thyroid phenotype.

PMID- 25602314
TI  - Dataset papers.

PMID- 25602313
TI  - Preclinical Safety Evaluation of ASCs Engineered by FLPo/Frt-Based Hybrid
      Baculovirus: In Vitro and Large Animal Studies.
AB  - We recently developed hybrid baculovirus (BV) vectors that exploited FLPo/Frt
      mediated DNA minicircle formation. Engineering of adipose-derived stem cells
      (ASCs) with the FLPo/Frt-based BV vectors enabled prolonged transgene expression
      and, after cell implantation into rabbits, ameliorated cartilage regeneration and
      bone repair. To translate the hybrid BV one step further toward clinical
      applications, here we assessed the biosafety profiles of the hybrid BV-engineered
      human ASCs (hASCs) in vitro and evaluated the immune responses elicited by the
      engineered porcine ASCs (pASCs) in large animals. We confirmed that the hybrid BV
      did not compromise the hASCs viability, immunosuppressive capacity, and surface
      characteristics. Neither did the hybrid BV cause chromosomal
      abnormality/transgene integration in vitro nor did it induce tumorigenicity in
      vivo. In the large animal study, pASCs were engineered with the hybrid BV
      expressing bone morphogenetic protein 2 (BMP2) and vascular endothelial growth
      factor (VEGF) and implanted into femoral bone defects in mini pigs. The hybrid BV
      engineered pASCs enabled prolonged BMP2/VEGF expression and triggered the healing
      of massive segmental bone defects, while only eliciting transient antibody,
      cytokine, and local cellular immune responses stemming from the implantation
      procedure itself. These data altogether demonstrated the safety of the hybrid BV
      vectors for ASCs engineering and bone healing in large animals, hence implicating
      the potential in clinical applications. 

PMID- 25602315
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      introduction, establishment, and overview.
AB  - Many challenges currently facing agriculture require long-term data on landscape
      scale hydrologic responses to weather, such as from the Goodwater Creek
      Experimental Watershed (GCEW), located in northeastern Missouri, USA. This
      watershed is prone to surface runoff despite shallow slopes, as a result of a
      significant smectitic clay layer 30 to 50 cm deep that restricts downward flow of
      water and gives rise to a periodic perched water table. This paper is the first
      in a series that documents the database developed from GCEW. The objectives of
      this paper are to (i) establish the context of long-term data and the federal
      infrastructure that provides it, (ii) describe the GCEW/ Central Mississippi
      River Basin (CMRB) establishment and the geophysical and anthropogenic context,
      (iii) summarize in brief the collected research results published using data from
      within GCEW, (iv) describe the series of papers this work introduces, and (v)
      identify knowledge gaps and research needs. The rationale for the collection
      derives from converging trends in data from long-term research, integration of
      multiple disciplines, and increasing public awareness of increasingly larger
      problems. The outcome of those trends includes being selected as the CMRB site in
      the USDA-ARS Long-Term Agro-Ecosystem Research (LTAR) network. Research needs
      include quantifying watershed scale fluxes of N, P, K, sediment, and energy,
      accounting for fluxes involving forest, livestock, and anthropogenic sources,
      scaling from near-term point-scale results to increasingly long and broad scales,
      and considering whole-system interactions. This special section informs the
      scientific community about this database and provides support for its future use
      in research to solve natural resource problems important to US agricultural,
      environmental, and science policy. 

PMID- 25602316
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      goodwater creek experimental watershed weather data.
AB  - Knowledge of weather, particularly precipitation, is fundamental to interpreting
      watershed and hydrologic processes. The long-term weather record in the Goodwater
      Creek Experimental Watershed (GCEW) complements hydrologic and water quality data
      in the region. The GCEW also is the core of the Central Mississippi River Basin
      (CMRB) node of the Long-Term Agroecosystem Research network. Our objectives are
      to (i) describe the climatological context of the GCEW and CMRB settings, (ii)
      document instrumentation and the data collection, quality assurance, and
      reduction processes; (iii) provide examples of the data obtained and descriptive
      statistics; and (iv) document the availability of and access methods to obtain
      the data from the web-based data access portal at . These objectives support an
      overall goal to make these long-term data available to the public for use in
      further analyses and modeling in support of research and public policy on
      watershed management. 

PMID- 25602317
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      goodwater creek experimental watershed flow data.
AB  - Flow monitoring in Goodwater Creek Experimental Watershed started in 1971 at
      three nested watersheds ranging from 12 to 73 km. Since then, runoff or stream
      flow has been measured at 14 plots, three fields, and 12 additional stream sites
      ranging from 0.0034 to 6067 km in the Central Mississippi River Basin. Long-term
      data sets are important to document the changes resulting from anthropogenic and
      natural drivers. The data set presented here documents discharge across a range
      of catchment sizes in an area known for its high runoff potential. It constitutes
      the flow database of the Central Mississippi River Basin site of the Long-Term
      Agricultural Research network. Like the other sites of this network, data are
      accessible through the STEWARDS web interface (). Here we (i) describe the data
      collection methods, (ii) document the data available at plot, field, and
      watershed scales, and (iii) provide the main characteristics of discharge.
      General characteristics of discharge per unit area for different cropping system
      management systems show that in this claypan soil setting, management and tillage
      of row crop systems do not affect surface flow during the growing season (April
      October). Data from fields and stream sites show the dampening of peak flow
      values and lengthening of storm hydrographs caused by mixed land uses and longer
      times of concentration. Overall, stream flow accounts for a third of the
      precipitation, of which 80% is from surface runoff and 20% is from groundwater. 

PMID- 25602318
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      goodwater creek experimental watershed and regional herbicide water quality data.
AB  - Goodwater Creek Experimental Watershed (GCEW) has been the focus area of a long
      term effort to document the extent of and to understand the factors controlling
      herbicide transport. We document the datasets generated in the 20-yr-long
      research effort to study the transport of herbicides to surface and groundwater
      in the GCEW. This long-term effort was augmented with a spatially broad effort
      within the Central Mississippi River Basin encompassing 12 related claypan
      watersheds in the Salt River Basin, two cave streams on the fringe of the Central
      Claypan Areas in the Bonne Femme watershed, and 95 streams in northern Missouri
      and southern Iowa. Details of the analytical methods, periods of record, number
      of samples, study locations, and means of accessing these data are provided. In
      addition, a brief overview of significant findings is presented. A key finding
      was that near-surface restrictive soil layers, such as argillic horizons of
      smectitic mineralogy, result in greater herbicide transport than soils with high
      percolation and low clay content. Because of this, streams in the claypan soil
      watersheds of northeastern Missouri have exceptionally high herbicide
      concentrations and relative loads compared with other areas of the Corn Belt. 

PMID- 25602319
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      goodwater creek experimental watershed and regional nutrient water quality data.
AB  - We document the 20-yr-long research effort to study the transport of N and P to
      surface and groundwater in Goodwater Creek Experimental Watershed. We also
      document related efforts in nearby claypan watersheds and watersheds with
      contrasting soil and hydrologic conditions across the northern Missouri-southern
      Iowa region. Details of the analytical methods, instrumentation, method detection
      limits, and quality assurance program used to generate the data are described
      along with a brief overview of significant findings. Nutrient concentrations in
      streams were in the range associated with nuisance algal growth and presumed loss
      of aquatic invertebrate diversity. Incorporation of fertilizers was shown to be
      the most effective practice for reducing nutrient transport in runoff. Despite
      the claypan soils, NO leaching was a major fate for fertilizer N, and significant
      contamination of the glacial till aquifer has occurred when long-term fertilizer
      and manure N inputs exceeded crop N requirements. A key finding of these studies
      was that field areas with the poorest crop growth were also the most vulnerable
      to nutrient as well as sediment and herbicide transport. 

PMID- 25602320
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      dissolved nitrogen and phosphorus transport in a high-runoff-potential watershed.
AB  - Long-term monitoring data from agricultural watersheds are needed to determine if
      efforts to reduce nutrient transport from crop and pasture land have been
      effective. Goodwater Creek Experimental Watershed (GCEW), located in northeastern
      Missouri, is a high-runoff-potential watershed dominated by claypan soils. The
      objectives of this study were to: (i) summarize dissolved NH-N, NO-N, and PO-P
      flow-weighted concentrations (FWC), daily loads, and yields (unit area loads) in
      GCEW from 1992 to 2010; (ii) assess time trends and relationships between
      precipitation, land use, and fertilizer inputs and nutrient transport; and (iii)
      provide context to the GCEW data by comparisons with other Corn Belt watersheds.
      Significant declines in annual and quarterly FWCs and yields occurred for all
      three nutrient species during the study, and the decreases were most evident for
      NO-N. Substantial decreases in first- and fourth-quarter NO-N FWCs and daily
      loads and modest decreases in first-quarter PO-P daily loads were observed.
      Declines in NO-N and PO-P transport were attributed to decreased winter wheat (
      L.) and increased corn ( L.) production that shifted fertilizer application from
      fall to spring as well as to improved management, such as increased use of
      incorporation. Regression models and correlation analyses indicated that
      precipitation, land use, and fertilizer inputs were critical factors controlling
      transport. Within the Mississippi River Basin, NO-N yields in GCEW were much
      lower than in tile-drained areas, but PO-P yields were among the highest in the
      basin. Overall, results demonstrated that reductions in fall-applied fertilizer
      and improved fertilizer management reduced N and P transport in GCEW. 

PMID- 25602321
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      hydrogeologic controls and crop management influence on nitrates in loess and
      fractured glacial till.
AB  - Nitrogen from agriculture is known to be a primary source of groundwater NO-N.
      Research was conducted in a northeastern Missouri watershed to assess the impact
      of cropping systems on NO-N for a loess and fractured glacial till aquifer
      underlying claypan soils. Three cropped fields with 10 yr of similar management
      were each instrumented with 20 to 25 monitoring wells, 3 to 15 m in depth, in
      1991 to 1992. Wells were sampled and analyzed for NO-N at least annually from
      1991 to 2004. Initial NO-N concentrations were variable, ranging from
      undetectable to >24 mg L but averaged 7.0 mg L. Groundwater NO-N was
      significantly higher in Field 3, probably the result of concurrent applications
      of manure and N fertilizer before 1980. Overall changes in NO-N levels in Fields
      1 and 2 were generally small; however, NO-N levels for Field 3 have decreased an
      average of 0.28 mg L yr. Excessive loading of N into the matrix of the glacial
      till may have had a long-term impact on NO-N for this field. Despite the presence
      of dissolved O in the aquifer, evidence of denitrification in some upper
      landscape groundwater wells was found. The greatest decreases in NO-N
      concentration occurred as groundwater moved through an in-field tree line or
      through a riparian zone. While overall conclusions were complicated by the long
      term impact of past management, the capacity of the till to buffer changes,
      hydrogeologic variability found among wells, and the activity of biological
      processes, we conclude that cropping practices during this study did not increase
      glacial till NO-N. 

PMID- 25602322
TI  - Long-term agroecosystem research in the central Mississippi river basin:
      hyperspectral remote sensing of reservoir water quality.
AB  - In situ methods for estimating water quality parameters would facilitate efforts
      in spatial and temporal monitoring, and optical reflectance sensing has shown
      potential in this regard, particularly for chlorophyll, suspended sediment, and
      turbidity. The objective of this research was to develop and evaluate
      relationships between hyperspectral remote sensing and lake water quality
      parameters-chlorophyll, turbidity, and N and P species. Proximal hyperspectral
      water reflectance data were obtained on seven sampling dates for multiple arms of
      Mark Twain Lake, a large man-made reservoir in northeastern Missouri. Aerial
      hyperspectral data were also obtained on two dates. Water samples were collected
      and analyzed in the laboratory for chlorophyll, nutrients, and turbidity.
      Previously reported reflectance indices and full-spectrum (i.e., partial least
      squares regression) methods were used to develop relationships between spectral
      and water quality data. With the exception of dissolved NH, all measured water
      quality parameters were strongly related ( >= 0.7) to proximal reflectance across
      all measurement dates. Aerial hyperspectral sensing was somewhat less accurate
      than proximal sensing for the two measurement dates where both were obtained.
      Although full-spectrum calibrations were more accurate for chlorophyll and
      turbidity than results from previously reported models, those previous models
      performed better for an independent test set. Because extrapolation of estimation
      models to dates other than those used to calibrate the model greatly increased
      estimation error for some parameters, collection of calibration samples at each
      sensing date would be required for the most accurate remote sensing estimates of
      water quality. 

PMID- 25602323
TI  - Long-Term Agroecosystem Research in the Central Mississippi River Basin: SWAT
      Simulation of Flow and Water Quality in the Goodwater Creek Experimental
      Watershed.
AB  - Starting in 1971, stream flow and climatologic data have been collected in the
      Goodwater Creek Experimental Watershed, which is part of the Central Mississippi
      River Basin (CMRB) Long-Term Agroecosystem Research (LTAR) site. Since 1992,
      water quality and socio-economic data have complemented these data sets. Previous
      modeling efforts highlighted the challenges created by the presence of a claypan.
      Specific changes were introduced in the Soil and Water Assessment Tool (SWAT) (i)
      to better simulate percolation through and saturation above the claypan and (ii)
      to simulate the spatial and temporal distributions of the timing of field
      operations throughout the watershed. Our objectives were to document the changes
      introduced into the code, demonstrate that these changes improved simulation
      results, describe the model's parameterization, calibration, and validation, and
      assess atrazine [6-chloro--ethyl-'-(1-methylethyl)-1,3,5-triazine-2,4-diamine]
      management practices in the hydrologic context of claypan soils. Model
      calibration was achieved for 1993 to 2010 at a daily time step for flow and at a
      monthly time step for water quality constituents. The new percolation routines
      ensured correct balance between surface runoff and groundwater. The temporal
      heterogeneity of atrazine application ensured the correct frequency of daily
      atrazine loads. Atrazine incorporation by field cultivation resulted in a 17%
      simulated reduction in atrazine load without a significant increase in sediment
      yields. Reduced atrazine rates produced proportional reductions in simulated
      atrazine transport. The model can be used to estimate the impact of other
      drivers, e.g., changing aspects of climate, land use, cropping systems, tillage,
      or management practices, in this context. 

PMID- 25602324
TI  - Evaluating dispersion modeling options to estimate methane emissions from grazing
      beef cattle.
AB  - Enteric methane (CH) emission from cattle is a source of greenhouse gas and is an
      energy loss that contributes to production inefficiency for cattle. Direct
      measurements of enteric CH emissions are useful to quantify the magnitude and
      variation and to evaluate mitigation of this important greenhouse gas source. The
      objectives of this study were to evaluate the impact of stocking density of
      cattle and source configuration (i.e., point source vs. area source and elevation
      of area source) on CH emissions from grazing beef cattle in Queensland,
      Australia. This was accomplished using nonintrusive atmospheric measurements and
      a gas dispersion model. The average measured CH emission for the point and area
      source was between 240 and 250 g animal d over the entire study. There was no
      difference ( > 0.05) in emission when using an elevated area source (0.5 m) or a
      ground area source (0 m). For the point-source configuration, there was a
      difference in CH emission due to stocking density; likewise, some differences
      existed for the area-source emissions. This study demonstrates the flexibility of
      the area-source configuration of the dispersion model to estimate CH emissions
      even at a low stocking density. 

PMID- 25602325
TI  - Seasonal methane and nitrous oxide emissions of several rice cultivars in direct
      seeded systems.
AB  - An understanding of cultivar effects on field greenhouse gas (GHG) emissions in
      rice ( L.) systems is needed to improve the accuracy of predictive models used
      for estimating GHG emissions and to evaluate the GHG mitigation potential of
      different cultivars. We compared CH and NO emissions, global warming potential
      (GWP = NO + CH), yield-scaled GWP (GWP = GWP Mg grain), and plant growth
      characteristics of eight cultivars within four study sites in California and
      Arkansas. Nitrous oxide emissions were negligible (<10% of GWP) and were not
      different among cultivars. Seasonal CH emissions differed between cultivars by a
      factor of 2.1 and 1.4 at one California and one Arkansas site, respectively.
      Plant growth characteristics were generally not correlated with seasonal CH
      emissions; however, the strongest correlations were observed for shoot and total
      plant (root + shoot) biomass at heading ( = 0.60) at one California site and for
      grain at maturity ( = -0.95) at one Arkansas site. Although differences in GWP
      and GWP were observed, there were inconsistencies across sites, indicating the
      importance of the genotype * environment interaction. Overall, the cultivars with
      the lowest CH emissions, GWP, and GWP at the California and Arkansas sites were
      the lowest and highest yielding, respectively. These findings highlight the
      potential for breeding high-yielding cultivars with low GWP, the ideal scenario
      to achieve low GWP, but environmental conditions must also be considered. 

PMID- 25602326
TI  - Soil respiration as affected by long-term broiler litter application to a udult
      in the ozark highlands.
AB  - The United States produced 8.4 billion broiler chickens () and an estimated 10.1
      to 14.3 million Mg of broiler litter (BL) in 2012. Arkansas' production of 1
      billion broilers in 2012 produced an estimated 1.2 to 1.7 million Mg of BL, most
      of which was concentrated in the Ozark Highlands region of northwest Arkansas.
      Increased CO release from soils associated with agricultural practices has
      generated concerns regarding the contribution of certain agricultural management
      practices to global warming. The objectives of this study were to evaluate the
      effects of long-term (>6 yr) BL application to a Udult on soil respiration and
      annual C emissions and to determine the predictability of soil respiration based
      on soil temperature and moisture in the Ozark Highlands region of northwest
      Arkansas. Soil respiration was measured routinely between May 2009 and May 2012
      in response to annual BL application rates of 0, 5.6, and 11.2 Mg dry litter ha
      that began in 2003. Soil respiration varied ( < 0.01) with BL rate, measurement
      date, and year. Additions of BL stimulated respiration after application, and
      rainfall events after dry-soil conditions stimulated respiration in all years.
      Soil temperature at the 10-cm depth, 0- to 6-cm soil volumetric water content
      (VWC), and annual CO-C emissions were unaffected ( > 0.05) by BL application rate
      but differed ( < 0.01) among study years. Multiple regression indicated that soil
      respiration could be reasonably predicted using 2-cm-depth soil temperature (T)
      and the product of T and VWC as predictors ( = 0.52; < 0.01). Results indicate
      that organic amendments, such as BL, can stimulate release of CO from the soil to
      the atmosphere, potentially negatively affecting atmospheric greenhouse gas
      concentrations; thus, there may be application rates above which the benefits of
      organic amendments may be diminished by adverse environmental effects. Improved
      BL management strategies are needed to lessen the loss of CO from BL-amended
      soils. 

PMID- 25602327
TI  - Manure ammonia and hydrogen sulfide emissions from a Western dairy storage basin.
AB  - The reporting of ammonia (NH) and hydrogen sulfide (HS) emissions from dairies to
      the federal government depends on the magnitude of the emissions. However, little
      is known about their daily NH and HS emissions and what influences those
      emissions. Emissions of NH and HS from two manure storage basins at a 4400-head
      western free-stall dairy were measured intermittently over 2 yr. Each basin went
      through stages of filling, drying, and then removal of the manure during the
      study period. Emissions were determined using backward Lagrangian Stochastic and
      vertical radial plume methods. Ammonia emissions ranged from 35 to 59 kg d in one
      basin and from 86 to 90 kg d in a second basin, corresponding to a range of 7 to
      19 g d head. Basin NH emissions were highest during initial filling and when the
      manure was removed. Mean HS emissions ranged from 5 to 22 kg d (1.1-4.6 g d
      head). Basin HS emissions were highest when the basin was filling. Crusting of
      the basin surface reduced NH but not HS emissions. The cessation of basin filling
      reduced HS but not NH emissions. Air temperature and wind conditions were
      correlated with NH emissions. Barometric pressure decreases were correlated with
      episodic HS emissions. The variability in emissions with stage of manure handling
      and storage and meteorological conditions indicates that determining the maximum
      daily emissions and the annual emissions from such waste basins requires
      consideration of each stage in conjunction with the climatic conditions during
      the stage. 

PMID- 25602328
TI  - Effect of soil aeration and phosphate addition on the microbial bioavailability
      of carbon-14-glyphosate.
AB  - The adsorption, desorption, degradation, and mineralization of C-glyphosate [
      (phosphonomethyl)glycine] were examined in Catlin (a fine-silty, mixed,
      superactive, mesic Oxyaquic Argiudoll), Flanagan (a fine, smectitic, mesic Aquic
      Argiudoll), and Drummer (a fine-silty, mixed, superactive, mesic Typic
      Endoaquoll) soils under oxic and anoxic soil conditions. With the exception of
      the Drummer soil, soil aeration did not significantly alter the adsorption
      pattern of C-glyphosate to soils. Herbicide desorption was generally enhanced
      with anaerobiosis in all the soil types. Anoxic soils demonstrated slower
      microbial degradation and mineralization kinetics of C-glyphosate than oxic soils
      in all the soil types studied. Phosphate additions significantly reduced the
      adsorption of C-glyphosate to soils irrespective of soil aeration and confirmed
      the well-established competitive adsorption theory. The addition of soil
      phosphate stimulated degradation only in anoxic soils. The results from this
      research highlight the importance of soil redox conditions as an important factor
      affecting the bioavailability and mobility of glyphosate in soils. 

PMID- 25602329
TI  - Microbial metabolism alters pore water chemistry and increases consolidation of
      oil sands tailings.
AB  - Tailings produced during bitumen extraction from surface-mined oil sands ores
      (tar sands) comprise an aqueous suspension of clay particles that remain
      dispersed for decades in tailings ponds. Slow consolidation of the clays hinders
      water recovery for reuse and retards volume reduction, thereby increasing the
      environmental footprint of tailings ponds. We investigated mechanisms of tailings
      consolidation and revealed that indigenous anaerobic microorganisms altered
      porewater chemistry by producing CO and CH during metabolism of acetate added as
      a labile carbon amendment. Entrapped biogenic CO decreased tailings pH, thereby
      increasing calcium (Ca) and magnesium (Mg) cations and bicarbonate (HCO)
      concentrations in the porewater through dissolution of carbonate minerals.
      Soluble ions increased the porewater ionic strength, which, with higher
      exchangeable Ca and Mg, decreased the diffuse double layer of clays and increased
      consolidation of tailings compared with unamended tailings in which little
      microbial activity was observed. These results are relevant to effective tailings
      pond management strategies. 

PMID- 25602330
TI  - Assessment of potential soil degradation on agricultural land in the czech
      republic.
AB  - Many attempts have been made worldwide to develop methods to identify the areas
      most threatened by soil degradation. Some soils in afflicted areas may be
      irreversibly degraded and thus have very little resilience (the ability to
      restore themselves). For the purpose of assessing the current state of soil
      degradation in the Czech Republic (CZ) we have developed an overall indicator of
      land vulnerability to the threat of soil degradation on the basis of individual
      factors that contribute to soil degradation and are monitored on a long-term
      basis in various research worksites in the CZ. Individual degradation factors
      were divided into two groups: chemical and physical degradation. On the basis of
      principal component analysis, individual degradation factors were assigned a
      specific weight of influence. With the use of a GIS, the input factors of
      degradation were combined to create maps of chemical and physical soil
      degradation, and consequently a map of overall degradation-threatened soils for
      the CZ, along with a map of areas differentiated according to the prevailing type
      of degradation. Results showed that, at present, the most important degradation
      factor in the CZ is water erosion, followed by loss of organic matter.
      Statistical analysis showed that approximately 51% of agricultural land is
      moderately threatened in the CZ. 

PMID- 25602331
TI  - Environmental vulnerability and phosphorus fractions of areas with pig slurry
      applied to the soil.
AB  - The application of pig slurry as a fertilizer can cause soil and water
      contamination. Intrinsic characteristics of the environment may enhance this
      effect and influence the vulnerability of the agricultural system. The goal of
      this study was to evaluate the accumulation of soil P fractions in areas treated
      with pig slurry and in forest areas and to propose an evaluation of the areas'
      vulnerability to P contamination. Soil samples were collected from 10 areas with
      pig slurry applied to the soil and one in forest without a history of pig slurry
      application, all located in the Coruja and Bonito rivers microbasin at Braco do
      Norte, Santa Catarina, southern Brazil. Samples were prepared and subjected to P
      chemical fractionation. Two versions of the P index method, based on soil P forms
      or only on P extracted by Mehlich-1, were used to evaluate the environmental risk
      of the studied areas. Estimated soil losses were lower for the forest and natural
      pasture and highest in areas with black oat ( Schreb.)-corn ( L.) crop
      cultivation. Concentrations of P fractions, especially of organic and inorganic P
      extracted by 0.1 and 0.5 mol L NaOH and NaHCO and of inorganic P extracted by
      anion exchange resin and HCl, were higher in areas with a longer history and
      higher frequency of pig slurry applications. Vulnerability to P contamination was
      mainly influenced by soil P concentrations and soil losses in the studied areas.
      The P index based on Hedley's fractionation P forms resulted in a more accurate
      risk scoring of the studied areas than the P index based on the concentration of
      available P extracted by Mehlich-1. 

PMID- 25602332
TI  - Concentration and fractionation of heavy metals in the old yellow river estuary,
      china.
AB  - A sequential extraction procedure was applied to determine the concentration and
      fractionation characteristics of eight heavy metals (HMs) (Cu, Zn, Pb, Cd, Cr,
      Fe, Mn, and Ni) in a sediment core collected from the old Yellow River Estuary,
      China. The results revealed that the mean deposition rate of this sediment core,
      which spanned 87 yr (1925-2012), was approximately 0.5 cm yr. The mean
      concentrations and ranges of HMs were Cu: 26.9 (18.3-38.5), Zn: 76.4 (51.0-107),
      Pb: 37.3 (17.8-53.8), Cd: 0.23 (0.20-0.27), Cr: 84.7 (45.5-116), Fe: 24,000
      (16,500-31,700), Mn: 709 (388-1020), and Ni: 36.1 (24.8-47.2) mg kg (dry weight).
      Six HMs (Cu, Zn, Cr, Cd, Fe, and Ni) were present in their highest proportion in
      the residual fraction; their lowest proportion was observed in the exchangeable
      fraction. Lead primarily existed in the oxidizable or residual fraction.
      Manganese was mainly presented in the exchangeable fraction. The risk assessment
      code results revealed that the sediments displayed a low risk for Cu, Zn, Pb, Cr,
      Cd, Fe, Mn, and Ni. The HMs Cu, Zn, Cr, Cd, Mn, and Ni displayed minor enrichment
      in the sediment core, whereas for Pb, moderate contamination enrichment was
      observed. Overall, an increase in and total concentration of HMs occurred since
      1925 and reached a maximum value around 1980, after which there was a larger
      fluctuation or decline until 2012. We also found that the degree of HM pollution
      during the 1976-1996 period was less serious than before 1976. All the sediment
      samples exceeded the effect range low (ERL) for Ni, whereas 56.1, 7.32, and 17.1%
      exceeded the ERL values for Cr, Cu, and Pb; no samples exceeded the ERL for Zn or
      Cd. 

PMID- 25602333
TI  - Lead immobilization and phosphorus availability in phosphate-amended, mine
      contaminated soils.
AB  - Over a century of mining activities in the Coeur d'Alene mining district in Idaho
      have contaminated soils of the downstream basin with lead, arsenic, zinc, and
      cadmium. Elevated soil-Pb levels are a significant hazard to the health of humans
      and wildlife in the region. One in situ treatment approach for remediating Pb
      contaminated soils is application of phosphorus to promote the formation of lead
      phosphate minerals that have low solubility. However, this remediation strategy
      may result in excess P runoff to surface waters, which can lead to
      eutrophication, particularly when used in riparian areas. Research presented in
      this paper describes experiments in which monopotassium phosphate (KHPO) solution
      was applied to two Pb-contaminated soils from the Coeur d'Alene River valley to
      determine how P loading rates affect both Pb immobilization and P mobility and to
      determine if an optimal P amendment rate can be predicted. Toxicity
      characteristic leaching procedure extractions were used to assess changes in Pb
      availability for uptake by an organism or mobilization through the soil, and Bray
      extractions were used to assess P availability for leaching out of the soil
      system. For the two soils tested, increasing phosphate amendment caused
      decreasing Pb extractability. Phosphorus amendment rates above approximately 70
      mg kg, however, did not provide any additional Pb immobilization. Phosphorus
      availability increased with increasing phosphate application rate. An empirical
      relationship is presented that predicts extractable Pb as a function of
      extractable P. This relationship allows for prediction of the amount of Pb that
      can be immobilized at specified P leaching amounts, such as regulatory levels
      that have been established to minimize risks for surface water degradation.
      Results suggest that phosphate can be used to immobilize Pb in contaminated
      wetland or riparian areas without posing risks of P loading to surface waters. 

PMID- 25602334
TI  - Comparing nitrate sink strength in perennial filter strips at toeslopes of
      cropland watersheds.
AB  - Integration of perennial filter strips (PFS) into the toeslopes of agricultural
      watersheds may decrease downstream nitrate (NO) losses. However, long-term NO
      removal depends on the relative importance of several NO sinks in the PFS. Plant
      biomass and labile soil organic matter (SOM) are temporary NO sinks, while stable
      SOM is a long-term, but potentially finite, NO sink. In contrast, denitrification
      is a permanent NO sink. We investigated the relative importance of these NO sinks
      in PFS at the toeslope of row crop watersheds in Iowa. Using 25- * 30-cm in situ
      mesocosms, we added NO to PFS soils and quantified NO-N recovery in plant biomass
      and SOM after one growing season. Further, we compared NO-N recovery in
      particulate (relatively labile) and mineral-associated (relatively stable) SOM in
      mesocosms with and without growing perennial vegetation. To determine the
      potential importance of denitrification, we compared denitrification enzyme
      activity in soils from paired watersheds with and without PFS. Transfer of NO-N
      into labile and stable SOM pools was rapid and initially independent of growing
      vegetation. However, SOM and plant biomass were both relatively minor NO sinks,
      accounting for <30% of NO-N inputs. Denitrification enzyme activity data
      indicated that dissolved organic carbon derived from perennial vegetation
      increased potential denitrifier activity in PFS soils compared with row crop
      soils. Together, these results constrain SOM and plant biomass as NO sinks and
      indicate that denitrification was the most important NO sink in perennial filter
      strips over one growing season. 

PMID- 25602335
TI  - A STELLA Model to Estimate Water and Nitrogen Dynamics in a Short-Rotation Woody
      Crop Plantation.
AB  - Although short-rotation woody crop biomass production technology has demonstrated
      a promising potential to supply feedstocks for bioenergy production, the water
      and nutrient processes in the woody crop planation ecosystem are poorly
      understood. In this study, a computer model was developed to estimate the
      dynamics of water and nitrogen (N) species (e.g., NH-N, NO-N, particulate organic
      N, and soluble organic N [SON]) in a woody crop plantation using STELLA
      (tructural hinking and xperiential earning aboratory with nimation) software. A
      scenario was performed to estimate diurnal and monthly water and N variations of
      a 1-ha mature cottonwood plantation over a 1-yr simulation period. A typical
      monthly variation pattern was found for soil water evaporation, leaf water
      transpiration, and root water uptake, with an increase from winter to summer and
      a decrease from summer to the following winter. Simulations further revealed that
      the rate of soil water evaporation was one order of magnitude lower than that of
      leaf water transpiration. In most cases, the relative monthly water loss rates
      could be expressed as evapotranspiration > root uptake > percolation > runoff.
      Leaching of NO-N and SON depended not only on soil N content but also on rainfall
      rate and duration. Leaching of NO-N from the cottonwood plantation was about two
      times higher than that of SON. The relative monthly rate of N leaching was NO-N >
      SON > NH-N. This study suggests that the STELLA model developed is a useful tool
      for estimating water and N dynamics from a woody crop plantation. 

PMID- 25602336
TI  - Reactive nitrogen in turfgrass systems: relations to soil physical, chemical, and
      biological properties.
AB  - Turfgrass systems contribute to the loading of reactive N to water and air via
      runoff, leaching, and gas emission. Yet, a comprehensive approach has never been
      developed to assess N loss potential from turfgrass systems. We used pools and
      production of reactive N (inorganic N, extractable organic N, and NO) to estimate
      N loss potential and hypothesized that this potential could be predicated by
      basic soil properties. A total of 68 soil samples were taken from 17 bermudagrass
      sites in North Carolina. Basic soil properties were analyzed, including soil C
      and N, C:N ratio, microbial biomass, moisture, pH, and percent silt/clay/sand.
      Soil samples varied most widely in texture, followed by soil C and N, microbial
      biomass, moisture, pH, and C:N ratio. The pools of extractable organic N and
      inorganic N were comparable, indicating that soluble organic N should be
      considered as a pathway of N loss from turfgrass. Turfgrass with large pools and
      production of reactive N was characterized by high soil C and N, microbial
      biomass, and moisture. Because soil C and N accumulate over time after turfgrass
      establishment, turfgrass age could be a suitable practical indicator of N loss
      potential and thus could be used to implement changes in management. Pools and
      production of reactive N in liquid and gas phases were well correlated,
      suggesting that if a turfgrass system has a high potential of N loss via leaching
      and runoff, it may also be of a high potential for NO emissions. 

PMID- 25602337
TI  - Low-molecular-weight organic acids influence the sorption of phenanthrene by
      different soil particle size fractions.
AB  - The impact of low-molecular-weight organic acids (LMWOAs) on the sorption of
      phenanthrene (a representative polycyclic aromatic hydrocarbon) by different
      particle size fractions of a soil was investigated using a batch technique.
      Citric and malic acids were used in experiments. Four soil fractions were
      fractionated: fine sand, silt, coarse clay, and fine clay. Laser granulometry
      confirmed the suitability of the fractionation method used for the particle size
      distributions in this investigation. The sorption of phenanthrene by the
      different soil fractions was described well using a linear distribution-type
      model, and the distribution coefficients () followed a descending order of fine
      sand > fine clay > coarse clay > silt, irrespective of the addition of organic
      acids. This order was significantly positively correlated with the organic carbon
      content of test soil solids. The values for phenanthrene sorption by soil
      fractions initially increased but then decreased as the concentrations of citric
      and malic acids increased (0-1000 mmol L). The presence of citric and malic acid
      at lower concentrations (<100 mmol L) generally promoted the sorption of
      phenanthrene, while higher concentrations (>100 mmol L) inhibited sorption
      irrespective of the soil fraction. The mechanism of the LMWOA-influenced sorption
      of phenanthrene by test solids is discussed based on the observed sorption of
      organic acid, the dissolution of metal cations and minerals in soil, and the
      competition from dissolved organic matter in solution that were released from
      soil solids. 

PMID- 25602338
TI  - Optimal Thermolysis Conditions for Soil Carbon Storage on Plant Residue Burning:
      Modeling the Trade-Off between Thermal Decomposition and Subsequent
      Biodegradation.
AB  - Field burning of plant biomass is a widespread practice that provides charred
      materials to soils. Its impact on soil C sequestration remains unclear due to the
      heterogeneity of burning products and difficulty in monitoring the material's
      biodegradation in fields. Basic information is needed on the relationship between
      burning conditions and the resulting quantity/quality of residue-derived C
      altered by thermal decomposition and biodegradation. In this study, we
      thermolyzed residues (rice straw and husk) at different temperatures (200-600
      degrees C) under two oxygen availability conditions and measured thermal mass
      loss, C compositional change by solid-state C NMR spectroscopy, and
      biodegradability of the thermally altered residues by laboratory aerobic
      incubation. A trade-off existed between thermal and microbial decomposition: when
      burned at higher temperatures, residues experience a greater mass loss but become
      more recalcitrant via carbonization. When an empirical model accounting for the
      observed trade-off was projected over 10 to 10 yr, we identified the threshold
      temperature range (330-400 degrees C) above and below which remaining residue C
      is strongly reduced. This temperature range corresponded to the major loss of O
      alkyl C and increase in aromatic C. The O/C molar ratios of the resultant
      residues decreased to 0.2 to 0.4, comparable to those of chars in fire-prone
      field soils reported previously. Although the negative impacts of biomass burning
      need to be accounted for, the observed relationship may help to assess the long
      term fate of burning-derived C and to enhance soil C sequestration. 

PMID- 25602339
TI  - Rainfall-induced runoff from exposed streambed sediments: an important source of
      water pollution.
AB  - When surface water levels decline, exposed streambed sediments can be mobilized
      and washed into the water course when subjected to erosive rainfall. In this
      study, rainfall simulations were conducted over exposed sediments along stream
      banks at four distinct locations in an agriculturally dominated river basin with
      the objective of quantifying the potential for contaminant loading from these
      often overlooked runoff source areas. At each location, simulations were
      performed at three different sites. Nitrogen, phosphorus, sediment, fecal
      indicator bacteria, pathogenic bacteria, and microbial source tracking (MST)
      markers were examined in both prerainfall sediments and rainfall-induced runoff
      water. Runoff generation and sediment mobilization occurred quickly (10-150 s)
      after rainfall initiation. Temporal trends in runoff concentrations were highly
      variable within and between locations. Total runoff event loads were considered
      large for many pollutants considered. For instance, the maximum observed total
      phosphorus runoff load was on the order of 1.5 kg ha. Results also demonstrate
      that runoff from exposed sediments can be a source of pathogenic bacteria. spp.
      and spp. were present in runoff from one and three locations, respectively.
      Ruminant MST markers were also present in runoff from two locations, one of which
      hosted pasturing cattle with stream access. Overall, this study demonstrated that
      rainfall-induced runoff from exposed streambed sediments can be an important
      source of surface water pollution. 

PMID- 25602340
TI  - A farm-scale risk-index for reducing fecal contamination of surface waters.
AB  - There is increasing recognition of the adverse impacts of agricultural practices
      on microbial water quality leading to increased expectation on farmers to manage
      environmental impacts on water quality. Therefore, farmers require a tool to help
      them prioritize mitigations targeted at reducing fecal contamination of surface
      water. A farm-scale risk-index was developed from modeled data on the predicted
      losses of from selected farm practices. The farm-scale data were then converted
      to a catchment scale risk value and calibrated against stream concentration data
      measured in five catchments. The data from the five catchments indicate that
      there is a relationship between the risk of losses from some farm practices and
      the resulting levels in the streams. The results show that the adoption of
      existing mitigation options for fecal contamination should result in a
      substantial reduction of concentrations in streams flowing through catchments
      used for intensive dairy farming. However, the relatively high concentrations in
      the stream when the calculated risk-index values are low indicate that currently
      available mitigation practices may not be sufficient to achieve contact
      recreational water quality standards in many catchments due to other sources of .
      This risk-index approach can be incorporated into existing decision support tools
      to enable farmers to manage fecal contamination impacts from their farming
      operations. 

PMID- 25602341
TI  - Reducing nitrogen loss with managed drainage and polymer-coated urea.
AB  - Continuous corn ( L.) production during dry years combined with high N fertilizer
      rates can have a high potential for NO-N loss through tile drainage water.
      Claypan soils can further increase the potential for NO-N loss through tile
      drainage water due to the claypan layer that restricts N leaching below the tile
      drains. The objective of this 4-yr study was to determine whether use of managed
      subsurface drainage (MD) in combination with a controlled-release N fertilizer
      could reduce the annual amount of NO-N loss through tile drainage water compared
      with free subsurface tile drainage (FD) with a noncoated urea application. Due to
      dry conditions over the summer and fall months, MD reduced the annual amount of
      water drained by at least 73% compared with FD in two of the four crop years. Low
      N loss and reduced corn N uptake possibly resulted in carry-over N and high soil
      N concentrations throughout the study, which may have limited the effect of N
      fertilizer source on annual NO-N loss in the tile drainage water. Use of MD
      reduced annual NO-N loss in the tile drainage water by 78 to 85% in two of the
      four years. High NO-N loss reduction with MD compared with FD was largely due to
      dry growing season conditions in combination with wet conditions over the
      noncropping period. 

PMID- 25602342
TI  - Determining pathogen and indicator levels in class B municipal organic residuals
      used for land application.
AB  - Biosolids are nutrient-rich organic residuals that are currently used to amend
      soils for food production. Treatment requirements to inactivate pathogens for
      production of Class A biosolids are energy intensive. One less energy intensive
      alternative is to treat biosolids to Class B standards, but it could result in
      higher pathogen loads. Quantitative microbial risk assessments models have been
      developed on land application of Class B biosolids but contain many uncertainties
      because of limited data on specific pathogen densities and the use of fecal
      indicator organisms as accurate surrogates of pathogen loads. To address this
      gap, a 12-mo study of the levels and relationships between , , and human
      adenovirus (HAdV) with fecal coliform, somatic, and F-RNA coliphage levels in
      Class B biosolids from nine wastewater treatment plants throughout the United
      States was conducted. Results revealed that fecal coliform, somatic, and F-RNA
      coliphage densities were consistent throughout the year. More important, results
      revealed that HAdV ( = 2.5 * 10 genome copies dry g) and ( = 4.14 * 10 cysts dry
      g) were in all biosolids samples regardless of treatment processes, location, or
      season. oocysts were also detected (38% positive; range: 0-1.9 * 10 oocysts dry
      g), albeit sporadically. Positive correlations among three fecal indicator
      organisms and HAdV, but not protozoa, were also observed. Overall, this study
      reveals that high concentrations of enteric pathogens (e.g., , , and HAdV) are
      present in biosolids throughout the United States. Microbial densities found can
      further assist management and policymakers in establishing more accurate risk
      assessment models associated with land application of Class B biosolids. 

PMID- 25602343
TI  - Metal leaching in mine tailings: short-term impact of biochar and wood ash
      amendments.
AB  - Biochar is perceived as a promising amendment to reclaim degraded, metal
      contaminated lands. The objective of this study was to compare the potential of
      biochar and wood ash amendments to reduce metal(loid) leaching in mine tailings.
      A 2-mo leaching experiment was conducted in duplicate on acidic and alkaline
      tailings, each mixed with 5 wt.% of one of the following amendments: three wood
      derived, fast-pyrolysis biochars (OC > 57 wt.%) and two wood ash materials
      (organic carbon [OC] <= 16 wt.%); a control test with no carbon input was also
      added. The columns were leached with water after 1, 2, 4, 8, 16, 32, and 64 d,
      and the leachates were monitored for dissolved metals, OC, and pH. For the acidic
      and alkaline tailings, the most significant impact on metal mobility was observed
      with wood ash materials due to their greater neutralization potential (>15% CaCO
      eq.) compared with biochar (<=3.3% CaCO eq.). An increase of 1 pH unit in the
      wood ash-treated alkaline tailings led to an undesirable mobilization of As and
      Se. The addition of biochar did not significantly reduce the leaching of the main
      contaminants (Cu and Ni in the acidic tailings and As in the alkaline tailings)
      over 2 mo. The Se attenuation noted in some biochar-treated acid tailings may be
      mainly due to a slight alkaline effect rather than Se removal by biochar, given
      the low capacity for the fresh biochars to retain Se under acidic conditions (pH
      4.5). The increased loss of dissolved OC in the biochar-amended systems was of
      short duration and was not associated with metal(loid) mobilization. 

PMID- 25602344
TI  - Uptake coefficients for biosolids-amended dryland winter wheat.
AB  - The USEPA adapted a risk assessment approach in biosolids regulations that
      includes the use of an uptake coefficient (UC) (i.e., the ratio of plant
      concentration to quantity of element added) to determine limitations on selected
      elemental additions. The nature of the risk assessment requires UCs to be
      constants. Our hypothesis was that the UC for Cu, Fe, Mo, Ni, P, and Zn for
      biosolids-amended dryland winter wheat ( L.) decreases with multiple biosolids
      applications at the same location. We applied up to 10 applications to two sites
      (designated North Bennett A and B) in eastern Colorado at rates from 2.24 to 11.2
      Mg ha per application from 1993 to 2013. Results indicated that grain
      concentrations for all six elements followed no discernible trend as the number
      of biosolids applications increased. The UC values for these elements compared
      with the number of biosolids applications followed exponential decay models (
      ranged from 0.329 to 0.879). Consequently, UC values will likely not provide
      constants for risk assessment where multiple biosolids applications are made on
      the same site. We found that the slope between cumulative elemental removal by
      grain (kg ha) to the cumulative amount of element added with biosolids (kg ha)
      provides a constant over the number of biosolids additions ( ranged from 0.471 to
      0.990). As compared with the USEPA approach, our strategy of looking at
      cumulative changes may provide better estimations of wheat-grain concentrations
      for risk assessment of biosolids-borne elements. 

PMID- 25602345
TI  - Measuring solid percentage of oil sands mature fine tailings using the dual probe
      heat pulse method.
AB  - The reclamation of mature fine tailings (MFT) is a critical challenge for the oil
      sands industry in western Canada, and a nonradioactive, automated, and
      inexpensive method to monitor the MFT solidification is needed. The objective of
      this paper is to evaluate the feasibility of a dual-probe heat pulse (DPHP)
      method to measure MFT solid percentage. Dual-probe heat pulse measurements were
      performed on three MFT samples, each at various solid percentages. A linear
      relationship ( = 0.9495 + 0.0558) was established between the DPHP-measured solid
      percentage () and that of oven-dry method (). Six additional MFT samples were
      collected and measured to validate the DPHP method. The specific heats of the six
      MFT solids were measured independently using a modulated differential scanning
      calorimetry method, and the sensitivity of DPHP-measured MFT solid percentage to
      the specific heat of MFT solids was evaluated. The result shows that the DPHP
      method can be used to accurately measure MFT solid percentages, and the accuracy
      can be further improved if the specific heat of the MFT solids is measured
      independently. 

PMID- 25602346
TI  - Persistence of pharmaceuticals in effluent-dominated surface waters.
AB  - Pharmaceutical fate in surface water depends on a combination of physical and
      chemical processes, but currently, little information is available on cumulative
      dissipation rates in effluent-dominated receiving waters. In this study,
      dissipation rates were calculated for pharmaceutical compounds in two streams
      receiving municipal wastewater effluents using results from passive samplers.
      Seventeen pharmaceuticals were detected at the two sampling locations, and first
      order dissipation rates were found to range between 0.03 and -0.02 h, indicating
      that some compounds were conserved, while others rapidly dissipated over several
      kilometers downstream of the source. 

PMID- 25602347
TI  - Growth hormone receptor gene expression in puberty.
AB  - The mechanisms regulating the synergic effect of growth hormone and other
      hormones during pubertal spurt are not completely clarified. We enrolled 64
      females of Caucasian origin and normal height including 22 prepubertal girls, 26
      pubertal girls, and 16 adults to evaluate the role of Growth Hormone/Insulin-like
      growth factor-I axis (GH/IGF-I) during the pubertal period. In these subjects
      both serum IGF-I and growth hormone binding protein levels, as well as
      quantitative growth hormone receptor (GHR) gene expression were evaluated in
      peripheral lymphocytes of all individuals by real-time PCR. Our results showed
      significantly lower IGF-I levels in women (148+/-10 ng/ml) and prepubertal girls
      (166.34+/-18.85 ng/ml) compared to pubertal girls (441.95+/-29.42 ng/ml;
      p<0.0001). Serum GHBP levels were significantly higher in prepubertal (127.02+/
      20.76 ng/ml) compared to pubertal girls (16.63+/-2.97 ng/ml; p=0.0001) and adult
      women (19.95+/-6.65 ng/ml; p=0.0003). We also found higher GHR gene expression
      levels in pubertal girls [174.73+/-80.22 ag (growth hormone receptor)/5*10(5) ag
      (glyceraldehyde 3-phosphate dehydrogenase)] compared with other groups of
      subjects [women: 42.52+/-7.66 ag (growth hormone receptor)/5*10(5) ag
      (glyceraldehyde 3-phosphate dehydrogenase); prepubertal girls: 58.45+/-0.18.12 ag
      (growth hormone receptor)/5*10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)],
      but the difference did not reach statistical significance. These results suggest
      that sexual hormones could positively influence GHR action, during the pubertal
      period, in a dual mode, that is, increasing GHR mRNA production and reducing GHR
      cleavage leading to GHBP variations. 

PMID- 25602348
TI  - The VGF-Derived Neuropeptide TLQP-21 Shows No Impact on Hormone Secretion in the
      Isolated Perfused Rat Pancreas.
AB  - TLQP-21 is a VGF-derived neuropeptide proposed to be involved in regulation of
      metabolism. More specifically it has been suggested that TLQP-21 has the ability
      to enhance glucose stimulated insulin secretion, making it a candidate for
      treatment of patients with type 2 diabetes.In this study, we investigated the
      impact of TLQP-21 on insulin, glucagon, and somatostatin secretion in the
      perfused rat pancreas. We found that administration of 5 and 50 nM TLQP-21 had no
      impact on pancreatic hormone secretion at 3.5 or 8 mM glucose levels. Increasing
      TLQP-21 (200 nM) and glucose concentration (3.5 and 16 mM) led to a
      nonsignificant decrease in glucagon secretion, though insulin and somatostatin
      secretory patterns remained unaffected. In a final set of experiments, perfusions
      were performed with infusion of 50 and 1 000 nM TLQP-21 to ensure sufficient
      stimulation. However, administration of TLQP-21 under this setup showed no impact
      on the pancreatic hormone secretion either. In conclusion, the outcome of this
      study does not concur with previous findings, suggesting that the effect of TLQP
      21 does not directly involve silent hormone secretion. 

PMID- 25602349
TI  - Crosstalk Between Glycoxidative Modification of Low-Density Lipoprotein,
      Angiotensin II-Sensitization, and Adrenocortical Aldosterone Release.
AB  - Low-density lipoprotein (LDL) is considered to be a risk factor for
      atherosclerosis. In the presence of hyperglycemia, LDL undergoes glycoxidative
      modification and this glycoxidized (glycox) LDL promotes atherosclerosis in type
      2 diabetic (T2D) individuals. Moreover, because of its cholesterol content, LDL
      contributes to aldosterone biosynthesis, which is modulated by angiotensin II
      (AngII) and has been implicated in cardiovascular complications of T2D. However,
      the molecular mechanism of the crosstalk between glycoxLDL, AngII, and
      aldosterone has not been explained clearly. Therefore, this study has been aimed
      to investigate the impact of in vitro modified glycoxLDL on aldosterone release
      in an AngII-sensitized adrenocortical carcinoma cell line (NCI H295R). Native LDL
      (natLDL), isolated from healthy volunteers by sequential density gradient
      ultracentrifugation, was subjected to d-glucose (200 mmol/l), for glycoxidative
      modification, at 37  degrees C for 6 days. The AngII-sensitized H295R cells were
      treated with natLDL and glycoxLDL for 24 h and the supernatant was used for
      aldosterone measurement. The treated cells were utilized for protein isolation
      and mRNA quantification. Compared to natLDL, glycoxLDL produced a significantly
      greater effect on aldosterone release from AngII-sensitized cells. The treatment
      with specific pharmacological inhibitors suggests that modified LDL recruits
      ERK1/2 and janus kinase-2 for transcriptional regulation of aldosterone synthase.
      Moreover, glycoxLDL modulates aldosterone release via cAMP-dependent protein
      kinase A (PKA) pathway. However, glycoxLDL induces ERK phosphorylation
      independent of PKA activation and this novel mechanism could be targeted for
      therapeutic trials. In conclusion, this in vitro study emphasizes a possible
      causal relationship between LDL glycoxidative modification, AngII-sensitization,
      and adrenocortical steroid hormone release.

PMID- 25602350
TI  - Marginal Leakage of Class V Composite Restorations Assessed Using Microcomputed
      Tomography and Scanning Electron Microscope.
AB  - OBJECTIVE: The aim of the study was to compare in Class V composite restorations
      marginal leakage measurements obtained with microcomputed tomography (micro-CT)
      and scanning electron microscopy (SEM) observations. METHODS: Class V cavities
      were prepared on 10 human molars and restored using Optibond FL (Kerr, Orange,
      CA, USA) and Premise Flowable (Kerr). Sealing ability was evaluated by assessing
      silver-nitrate penetration depth along enamel and dentin margins. Leakage was
      quantified using a scoring system. Micro-CT analysis provided 502 cross-sectional
      images for each tooth. Microleakage evaluation was performed first on three cross
      sections corresponding to the sections examined by SEM, then on all 502 of the
      obtained micro-CT images. SEM observations were performed first at 20*
      magnification, then, if showing a zero score, at 80* magnification. Enamel and
      dentin microleakage scores assigned to corresponding sections through micro-CT
      and SEM (20*) were compared (Wilcoxon signed-rank test, alpha=0.05). RESULTS: No
      statistically significant difference in leakage scores emerged between micro-CT
      and 20*-magnification SEM. Eight tooth sections that were given a zero score
      under SEM at 20* magnification showed to be infiltrated at the higher
      magnification (80*). For five teeth a higher score was assigned following
      scanning of 502 cross-sections than based on the observation of three sections.
      CONCLUSIONS: Micro-CT presents as a valid, nondestructive in vitro method to
      quantitatively evaluate marginal leakage of adhesive restorations.

PMID- 25602352
TI  - Deep in the heart of Texas: A phenomenological exploration of unsheltered
      homelessness.
AB  - The purpose of this qualitative study was to develop an in-depth understanding of
      the experience of unsheltered homelessness in Fort Worth, Texas. Eighteen
      individuals participated in the study; 13 were full-time residents of Fort Worth
      and 5 were traveling through the area via freight train. All reported long-term
      histories of unsheltered homelessness. Interviews were conducted in naturalistic
      settings; for example, on the street, under bridges, and in camps. Results
      indicated that the participants entered homelessness through diverse paths, but
      all of these paths were characterized by loss and social isolation. Many
      described homelessness as a threatening and dangerous experience; relying on
      strong street-based social networks and their own personal strengths for
      survival. Participants viewed shelter service providers as sources of stress and
      stigma to be avoided but heavily utilized street outreach services and faith
      based missions. The overemphasis by providers on "fixing" people, rather than
      addressing immediate needs, made many participants ambivalent about traditional
      services. This study supports the use of nontraditional housing interventions and
      robust community-based approaches to care for individuals experiencing
      unsheltered homelessness.

PMID- 25602353
TI  - Thermally highly stable amorphous zinc phosphate intermediates during the
      formation of zinc phosphate hydrate.
AB  - The mechanisms by which amorphous intermediates transform into crystalline
      materials are still poorly understood. Here we attempt to illuminate the
      formation of an amorphous precursor by investigating the crystallization process
      of zinc phosphate hydrate. This work shows that amorphous zinc phosphate (AZP)
      nanoparticles precipitate from aqueous solutions prior to the crystalline hopeite
      phase at low concentrations and in the absence of additives at room temperature.
      AZP nanoparticles are thermally stable against crystallization even at 400 
      degrees C (resulting in a high temperature AZP), but they crystallize rapidly in
      the presence of water if the reaction is not interrupted. X-ray powder
      diffraction with high-energy synchrotron radiation, scanning and transmission
      electron microscopy, selected area electron diffraction, and small-angle X-ray
      scattering showed the particle size (~20 nm) and confirmed the noncrystallinity
      of the nanoparticle intermediates. Energy dispersive X-ray, infrared, and Raman
      spectroscopy, inductively coupled plasma mass spectrometry, and optical emission
      spectrometry as well as thermal analysis were used for further compositional
      characterization of the as synthesized nanomaterial. (1)H solid-state NMR allowed
      the quantification of the hydrogen content, while an analysis of (31)P{(1)H} C
      rotational echo double resonance spectra permitted a dynamic and structural
      analysis of the crystallization pathway to hopeite. 

PMID- 25602354
TI  - Heredity of port-wine stains: investigation of families without a RASA1 mutation.
AB  - BACKGROUND: The prevalence of capillary malformations, also known as port-wine
      stains (PWS), is 0.3%. Familial segregation can occur. The capillary malformation
      arteriovenous malformation (CM-AVM) phenotype is caused by mutations in the RASA1
      gene. In PWS familial cases, the inheritance is considered to be autosomal
      dominant with variable penetrance. OBJECTIVE: Investigation of the heredity of
      PWS among patients who attended the vascular anomaly section at the Department of
      Dermatology in Malmoe, Southern Sweden, between 1993 and 2004 and to study the
      involvement of the RASA1 gene in patients with a positive family history of PWS.
      SUBJECTS AND METHODS: A total of 254 patients were examined and given a
      questionnaire regarding family history of PWS. The first group of 175 patients
      (109 females and 66 males) reported a negative family history. The other group of
      65 patients (46 females and 19 males) reported a positive family history (50%
      parents or brothers and sisters). RESULTS: The heredity of PWS was 27% (65/240).
      Twenty-one patients with a positive family history and relatives had no CM-AVM
      phenotype for mutations in the RASA1 gene. CONCLUSION: PWS may have a stronger
      heredity component than it was reported earlier and inheritance should be
      considered when counseling a patient. RASA1 mutations do not explain the PWS in
      our patients.

PMID- 25602355
TI  - Low-pulse energy Q-switched Nd:YAG laser treatment for hair-dye-induced Riehl's
      melanosis.
AB  - Riehl's melanosis, a form of dermatitis characterized by reticulate pigmentation,
      typically presents as a gray-brown to black hyperpigmentation on the face and
      neck. Among the various etiologic factors suggested, photoallergic reaction and
      pigmented contact dermatitis resulting from exposure to drugs, coal tar dyes,
      optical whitener, or other ingredients found in cosmetics are believed to be the
      major contributing factors in this disease. The histopathological features of
      Riehl's melanosis mainly consist of pigmentary incontinence along with
      infiltration of numerous dermal melanophages and lymphohistiocytes.1,2
      Additionally, notable clinical improvements in the treatment of this condition
      have been reported for intense pulsed light (IPL) therapy, in comparison to long
      term topical application of bleaching agents.2 Here, we report the cases of two
      Asian patients treated with a low-pulse energy 1,064-nm Q-switched (QS) Nd:YAG
      laser for hair dye-induced Riehl's melanosis on the face and neck. In conclusion,
      we observed that Riehl's melanosis on the face and neck was effectively and
      safely treated with a low-pulse energy 1,064-nm QS Nd:YAG laser. We suggest that
      this method can be used in Asian patients with Riehl's melanosis at risk of
      postinflammatory hyperpigmentation from excessive light or laser energy delivery.

PMID- 25602351
TI  - Creating an African HIV clinical research and prevention trials network: HIV
      prevalence, incidence and transmission.
AB  - HIV epidemiology informs prevention trial design and program planning. Nine
      clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational
      epidemiology studies in populations at risk for HIV infection as part of an HIV
      prevention and vaccine trial network. Annual HIV incidence ranged from below 2%
      to above 10% and varied by CRC and risk group, with rates above 5% observed in
      Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria
      fishing communities, men who have sex with men, and several cohorts of women. HIV
      incidence tended to fall after the first three months in the study and over
      calendar time. Among suspected transmission pairs, 28% of HIV infections were not
      from the reported partner. Volunteers with high incidence were successfully
      identified and enrolled into large scale cohort studies. Over a quarter of new
      cases in couples acquired infection from persons other than the suspected
      transmitting partner. 

PMID- 25602356
TI  - Three-dimensional volumetric assessment of body sculpting using a uniform heating
      radio frequency device in Asians.
AB  - BACKGROUND AND OBJECTIVES: A uniform heating radio frequency (RF) device induces
      thermal damage to adipose tissue by a controlled electric field that heats up fat
      preferentially. The objective of the study was to investigate the effect of RF
      treatments on body sculpting, as assessed by objective volumetric assessments.
      MATERIALS AND METHODS: Twenty Japanese patients were treated on requested body
      areas. A monopolar 1-MHz RF device with uniform heating and perpendicular
      internal electric fields was used to achieve greater heating within the fat. Two
      treatments were performed 6 weeks apart using a stamp method with 0-20% overlap.
      Depending on patient comfort, the temperatures were set between 44 and 46 degrees
      C. No topical anesthetics or any adjunctive treatment were administered before,
      during, or after the treatment. Super-imposable three-dimensional (3D)
      photographs were taken at baseline and 12 weeks post-second treatment. Patients
      rated their satisfaction using a 5-point scale. RESULTS: Objective assessments
      with super-imposable 3D color images showed statistically significant median
      volume reduction of 52.9 mL after treatments. Eighty percent of the patients were
      either "satisfied" or "very satisfied" with the results. No epidermal burns,
      sensory changes, and muscle contractions were observed. CONCLUSIONS: The uniform
      heating RF treatment is safe and effective for non-invasive body sculpting.

PMID- 25602357
TI  - Amphiphilic and Thermoresponsive Conjugated Block Copolymer with Its Solvent
      Dependent Optical and Photoluminescence Properties: Toward Sensing Applications.
AB  - Herein, we present a new class of amphiphilic, thermoresponsive rod-coil
      conjugated block copolymer having regioregular poly(3-hexyl thiophene) and poly(N
      isopropylacrylamide). Optical and luminescence properties of theses polymers
      significantly depend on the self-assembled nanostructures formed in different
      solvent and are easily tailored by chnaging the solvent composition or external
      stimuli like heat. Unique optical and electronic properties of this block
      copolymer are believed to make it promising for applications like sensor,
      fluorescence thermometer, optoelectronic, and bioelectronics devices. 

PMID- 25602359
TI  - Assessment of Alzheimer's disease symptom recognition in Korean Americans and
      psychometric analysis of Alzheimer's Disease Symptom Recognition Scale (ADSRS).
AB  - This study examined recognition of Alzheimer's disease symptoms among Korean
      Americans (KAs) and assessed psychometric properties of the Alzheimer's Disease
      Symptom Recognition Scale (ADSRS). A cross-sectional survey collected data from
      209 KAs, using a self-administered questionnaire. Results show that KAs
      recognized symptoms related to memory and cognitive functioning well, but had
      very limited recognition of neuropsychiatric symptoms. Psychometric analysis of
      ADSRS identified 4 factors in their symptom recognition. Findings suggest a need
      to raise awareness of Alzheimer's symptoms over the course of the disease.
      Assessment using ADSRS can be incorporated in communication in the practice
      context and public outreach. 

PMID- 25602360
TI  - Absence of pharmacodynamic interaction between inclacumab and heparin in healthy
      smokers.
AB  - Inclacumab is a novel monoclonal antibody directed against P-selectin in
      development for the prevention and treatment of atherosclerotic cardiovascular
      diseases. It is likely to be used concomitantly with heparin in patients
      undergoing percutaneous coronary intervention. Coadministration of both drugs may
      potentially increase the bleeding risk associated with heparin. This crossover
      study evaluated the potential pharmacodynamic interaction between inclacumab and
      unfractionated heparin in 18 healthy smokers. Owing to the long elimination of
      inclacumab (half-life of approximately 18 days), a 2-period, one-sequence study
      design was used. Subjects received an intravenous bolus injection of
      unfractionated heparin (5000 IU) on days 1 and 8 and an intravenous infusion of
      inclacumab (20 mg/kg) on day 8. Blood samples were collected on days 1 and 8 for
      pharmacodynamic effects of unfractionated heparin (anti-FXa and anti-FIIa
      activities, activated partial thromboplastin time and tissue factor pathway
      inhibitor) and over 6 months for pharmacokinetics of inclacumab. Sixteen subjects
      were eligible for pharmacodynamic analysis. Inclacumab had no clinically
      significant pharmacodynamic interaction with unfractionated heparin. With the
      exception of the minor but statistically significant increase of the maximum
      effect [Emax] of anti-FIIa activity, pharmacodynamic parameters (areas under the
      effect curve [AUElast] and Emax of anti-FXa) were almost similar on days 1 and 8.
      The 90% confidence intervals of geometric mean ratios of day 8 to day 1 for
      AUElast and Emax were however all contained within bioequivalence boundaries. The
      data demonstrate that the anticoagulant effect of unfractionated heparin was not
      affected by the administration of inclacumab. 

PMID- 25602358
TI  - Protocolized sedation vs usual care in pediatric patients mechanically ventilated
      for acute respiratory failure: a randomized clinical trial.
AB  - IMPORTANCE: Protocolized sedation improves clinical outcomes in critically ill
      adults, but its effect in children is unknown. OBJECTIVE: To determine whether
      critically ill children managed with a nurse-implemented, goal-directed sedation
      protocol experience fewer days of mechanical ventilation than patients receiving
      usual care. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial conducted
      in 31 US pediatric intensive care units (PICUs). A total of 2449 children (mean
      age, 4.7 years; range, 2 weeks to 17 years) mechanically ventilated for acute
      respiratory failure were enrolled in 2009-2013 and followed up until 72 hours
      after opioids were discontinued, 28 days, or hospital discharge. INTERVENTION:
      Intervention PICUs (17 sites; n = 1225 patients) used a protocol that included
      targeted sedation, arousal assessments, extubation readiness testing, sedation
      adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; n = 1224
      patients) managed sedation per usual care. MAIN OUTCOMES AND MEASURES: The
      primary outcome was duration of mechanical ventilation. Secondary outcomes
      included time to recovery from acute respiratory failure, duration of weaning
      from mechanical ventilation, neurological testing, PICU and hospital lengths of
      stay, in-hospital mortality, sedation-related adverse events, measures of
      sedative exposure (wakefulness, pain, and agitation), and occurrence of
      iatrogenic withdrawal. RESULTS: Duration of mechanical ventilation was not
      different between the 2 groups (intervention: median, 6.5 [IQR, 4.1-11.2] days;
      control: median, 6.5 [IQR, 3.7-12.1] days). Sedation-related adverse events
      including inadequate pain and sedation management, clinically significant
      iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were
      not significantly different between the 2 groups. Intervention patients
      experienced more postextubation stridor (7% vs 4%; P = .03) and fewer stage 2 or
      worse immobility-related pressure ulcers (<1% vs 2%; P = .001). In exploratory
      analyses, intervention patients had fewer days of opioid administration (median,
      9 [IQR, 5-15] days vs 10 [IQR, 4-21] days; P = .01), were exposed to fewer
      sedative classes (median, 2 [IQR, 2-3] classes vs 3 [IQR, 2-4] classes; P <
      .001), and were more often awake and calm while intubated (median, 86% [IQR, 67%
      100%] of days vs 75% [IQR, 50%-100%] of days; P = .004) than control patients,
      respectively; however, intervention patients had more days with any report of a
      pain score >= 4 (median, 50% [IQR, 27%-67%] of days vs 23% [IQR, 0%-46%] of days;
      P < .001) and any report of agitation (median, 60% [IQR, 33%-80%] vs 40% [IQR,
      13%-67%]; P = .003), respectively. CONCLUSIONS AND RELEVANCE: Among children
      undergoing mechanical ventilation for acute respiratory failure, the use of a
      sedation protocol compared with usual care did not reduce the duration of
      mechanical ventilation. Exploratory analyses of secondary outcomes suggest a
      complex relationship among wakefulness, pain, and agitation. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00814099.

PMID- 25602362
TI  - Self-efficacy and outcome expectations in cardiac rehabilitation: associations
      with women's physical activity.
AB  - OBJECTIVE: Little is known regarding the social-cognitive correlates of physical
      activity (PA) during and after cardiac rehabilitation (CR) in a female sample.
      The objective of the current study was to identify distinct trajectories for task
      self-efficacy, barrier self-efficacy, and outcome expectations and examine their
      association with PA. METHOD: A total of 203 women with cardiovascular disease
      completed a survey that included the self-efficacy, outcome-expectation, and PA
      measures at the beginning and end of CR, and 6 and 12 months after completing CR.
      RESULTS: Latent class growth analyses showed that multiple trajectories existed
      for task self-efficacy, barrier self-efficacy, and outcome expectations. Dual
      trajectory analyses showed that women in less favorable task self-efficacy,
      barrier self-efficacy, and outcome-expectation trajectories had a greater
      probability of being in an inactive PA trajectory. CONCLUSION/IMPLICATIONS: Women
      in trajectories with higher task and barrier self-efficacy and outcome
      expectations are more likely to be active, whereas the opposite is true for women
      with lower efficacy and outcome expectancies. As such, it is critical that health
      care practitioners incorporate strategies into their CR programs or professional
      practice after CR to increase women's confidence in engaging in PA, overcome
      barriers to engage in PA, and promote positive outcomes related to PA to increase
      their PA levels.

PMID- 25602361
TI  - Pain affects depression through anxiety, fatigue, and sleep in multiple
      sclerosis.
AB  - OBJECTIVE: Over a quarter million individuals in the United States have multiple
      sclerosis (MS). Chronic pain and depression are disproportionately high in this
      population. The purpose of this study was to examine the relationship between
      chronic pain and depression in MS and to examine potentially meditational effects
      of anxiety, fatigue, and sleep. METHOD: We used cross-sectional data from self
      reported instruments measuring multiple symptoms and quality of life indicators
      in this study. We used structural equation modeling to model direct and indirect
      effects of pain on depression in a sample of 1,245 community-dwelling individuals
      with MS. Pain interference, depression, fatigue, and sleep disturbance were
      modeled as latent variables with 2 to 3 indicators each. The model controlled for
      age, sex, disability status (Expanded Disability Status Scale), and social
      support. RESULTS: A model with indirect effects of pain on depression had
      adequate fit and accounted for nearly 80% of the variance in depression. The
      effects of chronic pain on depression were almost completely mediated by fatigue,
      anxiety, and sleep disturbance. Higher pain was associated with greater fatigue,
      anxiety, and sleep disturbance, which in turn were associated with higher levels
      of depression. The largest mediating effect was through fatigue. Additional
      analyses excluded items with common content and suggested that the meditational
      effects observed were not attributable to content overlap across scales.
      CONCLUSION: Individuals living with MS who report high levels of chronic pain and
      depressive symptoms may benefit from treatment approaches that can address sleep,
      fatigue, and anxiety.

PMID- 25602363
TI  - Synthesis and evaluation of 4-halogeno-N-[4-[6-(isopropylamino)pyrimidin-4-yl]
      1,3-thiazol-2-yl]-N-[11C]methylbenzamide for imaging of metabotropic glutamate 1
      receptor in melanoma.
AB  - Metabotropic glutamate 1 (mGlu1) receptor is found not only in the brain but also
      in melanomas and breast cancers. mGlu1 is a promising target for molecular
      imaging-based diagnosis and treatment of melanoma because its overexpression
      induces melanocyte carcinogenesis. Here we developed three PET tracers: 4
      halogeno-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol- 2-yl]-N
      [(11)C]methylbenzamide ([(11)C]4-6), which exhibited high uptake in target tumor
      and decreased uptake in nontarget brain tissues. In vitro binding assay indicated
      high to moderate binding affinities of 4-6 (Ki, 22-143 nM) for mGlu1 receptor. In
      vivo biodistribution studies in mice implanted with B16F10 melanoma cells
      confirmed high radioactive uptake in tumor and low uptake in blood, skin, and
      muscles. Inhibition of mGlu1 receptor using an mGlu1-selective ligand led to
      reduced radioactive uptake in the tumor. [(11)C]6 displayed the highest ratio of
      uptake between tumor and nontarget tissue and may prove useful as a PET tracer
      for mGlu1 imaging in melanoma. 

PMID- 25602364
TI  - GPs' negotiation strategies regarding sick leave for subjective health
      complaints.
AB  - OBJECTIVES: To explore general practitioners' (GPs') specific negotiation
      strategies regarding sick-leave issues with patients suffering from subjective
      health complaints. DESIGN: Focus-group study. SETTING: Nine focus-group
      interviews in three cities in different regions of Norway. PARTICIPANTS: 48 GPs
      (31 men, 17 women; age 32-65), participating in a course dealing with diagnostic
      practice and assessment of sickness certificates related to patients with
      subjective health complaints. RESULTS: The GPs identified some specific
      strategies that they claimed to apply when dealing with the question of sick
      leave for patients with subjective health complaints. The first step would be to
      build an alliance with the patient by complying with the wish for sick leave, and
      at the same time searching for information to acquire the patient's perspective.
      This position would become the basis for the main goal: motivating the patient
      for a rapid return to work by pointing out the positive effects of staying at
      work, making legal and moral arguments, and warning against long-term sick leave.
      Additional solutions might also be applied, such as involving other stakeholders
      in this process to provide alternatives to sick leave. CONCLUSIONS AND
      IMPLICATIONS: GPs seem to have a conscious approach to negotiations of sickness
      certification, as they report applying specific strategies to limit the duration
      of sick leave due to subjective health complaints. This give-and-take way of
      handling sick-leave negotiations has been suggested by others to enhance return
      to work, and should be further encouraged. However, specific effectiveness of
      this strategy is yet to be proven, and further investigation into the actual
      dealings between doctor and patients in these complex encounters is needed.

PMID- 25602366
TI  - MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by
      regulating the MAP4K4/c-Jun/MDM2 signaling pathway.
AB  - Tumor growth cascade is a complicated and multistep process with numerous
      obstacles. Until recently, evidences have shown the involvement of microRNAs
      (miRNAs) in tumorigenesis and tumor progression of various cancers, including
      colorectal cancer (CRC). In this study, we explored the role of miR-194 and its
      downstream pathway in CRC. We acquired data through miRNA microarray profiles,
      showing that the expression of miR-194 was significantly suppressed in CRC
      tissues compared with corresponding noncancerous tissues. Decreased miR-194
      expression was obviously associated with tumor size and tumor differentiation, as
      well as TNM stage. Both Kaplan-Meier and multivariate survival analysis showed
      that downregulated miR-194 was associated with overall survival. Moreover,
      functional assays indicated that overexpression of miR-194 in CRC cell lines
      inhibited cell proliferation both in vitro and in vivo. In addition, using dual
      luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194.
      Silencing of MAP4K4 resulted in similar biological behavior changes to that of
      overexpression of miR-194. We also observed through Human Gene Expression Array
      that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4
      downregulated MDM2 expression through transcription factor c-Jun binding to the 
      1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating
      the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and
      serve as a novel target for CRC prevention and therapy. 

PMID- 25602367
TI  - Ca2+ and endoplasmic reticulum Ca2+-ATPase regulate the formation of silk fibers
      with favorable mechanical properties.
AB  - Calcium ions (Ca(2+)) are crucial for the conformational transition of silk
      fibroin in vitro, and silk fibroin conformations correlate with the mechanical
      properties of silk fibers. To investigate the relationship between Ca(2+) and
      mechanical properties of silk fibers, CaCl2 was injected into silkworms (Bombyx
      mori). Fourier-transform infrared spectroscopy (FTIR) analysis and mechanical
      testing revealed that injection of CaCl2 solution (7.5mg/g body weight)
      significantly increased the levels of alpha-helix and random coil structures of
      silk proteins. In addition, extension of silk fibers increased after CaCl2
      injection. In mammals, sarcoplasmic reticulum Ca(2+)-ATPase in muscle and
      endoplasmic reticulum Ca(2+)-ATPase in other tissues (together denoted by SERCA)
      are responsible for calcium balance. Therefore, we analyzed the expression
      pattern of silkworm SERCA (BmSERCA) in silk glands and found that BmSERCA was
      abundant in the anterior silk gland (ASG). After injection of thapsigargin (TG)
      to block SERCA activity, silkworms showed a silk-spinning deficiency and their
      cocoons had higher calcium content compared to that of controls. Moreover, FTIR
      analysis revealed that the levels of alpha-helix and beta-sheet structures
      increased in silk fibers from TG-injected silkworms compared to controls. The
      results provide evidence that BmSERCA has a key function in calcium
      transportation in ASG that is related to maintaining a suitable ionic
      environment. This ionic environment with a proper Ca(2+) concentration is crucial
      for the formation of silk fibers with favorable mechanical performances. 

PMID- 25602365
TI  - Causes and consequences of protein folding stress in aneuploid cells.
AB  - Imbalanced chromosomal content, or aneuploidy, strongly affects the physiology of
      eukaryotic cells. The consequences of these effects are frequently detrimental,
      in particular in Metazoans. In humans, aneuploidy has been causatively linked to
      pathological conditions such as spontaneous abortions, trisomy syndromes and
      cancer. However, only in recent years have we witnessed an unraveling of the
      complex phenotypes that are caused by aneuploidy. Importantly, it has become
      apparent that aneuploidy evokes global and uniform changes that cannot be
      explained by the altered expression of the specific genes located on aneuploid
      chromosomes. Recent discoveries show that aneuploidy negatively affects protein
      folding; in particular, the functions of the molecular chaperone Heat Shock
      Protein 90 (HSP90) and the upstream regulator of heat shock-induced
      transcription, Heat Shock Factor 1 (HSF1), are impaired. Here we discuss the
      possible causes and consequences of this impairment and propose that the protein
      folding stress instigated by aneuploidy may be a common feature of conditions as
      variable as cancer and trisomy syndromes. 

PMID- 25602368
TI  - Selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3
      that impairs cancer cell survival.
AB  - Platelet-activating factor acetylhydrolases (PAFAHs) 1b2 and 1b3 are poorly
      characterized serine hydrolases that form a complex with a noncatalytic protein
      (1b1) to regulate brain development, spermatogenesis, and cancer pathogenesis.
      Determining physiological substrates and biochemical functions for the PAFAH1b
      complex would benefit from selective chemical probes that can perturb its
      activity in living systems. Here, we report a class of tetrahydropyridine
      reversible inhibitors of PAFAH1b2/3 discovered using a fluorescence polarization
      activity-based protein profiling (fluopol-ABPP) screen of the NIH 300,000+
      compound library. The most potent of these agents, P11, exhibited IC50 values of
      ~40 and 900 nM for PAFAH1b2 and 1b3, respectively. We confirm selective
      inhibition of PAFAH1b2/3 in cancer cells by P11 using an ABPP protocol adapted
      for in situ analysis of reversible inhibitors and show that this compound impairs
      tumor cell survival, supporting a role for PAFAH1b2/3 in cancer.

PMID- 25602371
TI  - Self-assembled metallic nanowire-based vertical organic field-effect transistor.
AB  - We report on in situ, self-assembly, solution-processing of metallic (Au/Ag)
      nanowire-based transparent electrodes integrated to vertical organic field-effect
      transistors (VOFETs). In the VOFET architecture, the nanowires' microstructure
      facilitates current modulation by the gate across the otherwise shielding
      sandwiched source electrode. We show N-type VOFETs operation with on/off ratio ~1
      * 10(5) and high current density (>1 mA cm(-2) at VDS = 5 V). The integration of
      the device design and the transparent electrode deposition methods offers a
      potential route for all-solution processing-based, large-area, high-efficiency
      organic electronics. 

PMID- 25602369
TI  - CHIP Is an Essential Determinant of Neuronal Mitochondrial Stress Signaling.
AB  - AIMS: Determine the mechanism by which C-terminus of HSC70-interacting protein
      (CHIP) induction alters neuronal survival under conditions of mitochondrial
      stress induced by oxygen glucose deprivation. RESULTS: We report that animals
      deficient in the E3 ubiquitin ligase, CHIP, have high baseline levels of central
      nervous system protein oxidation and lipid peroxidation, reduced antioxidant
      defenses, and decreased energetic status. Stress-associated molecules typically
      linked to Parkinson's disease such as the mitochondrial kinase, PTEN-inducible
      putative kinase 1 (PINK1), and another E3 ligase, Parkin, are upregulated in
      brains from CHIP knockout (KO) animals. Utilizing a novel biotin-avidin capture
      technique, we found that the oxidation status of Parkin and the mitochondrial
      fission protein, dynamin-related protein 1 (Drp1), are altered in a CHIP
      dependent manner. We also found that following oxygen-glucose deprivation (OGD),
      the expression of CHIP, PINK1, and the autophagic marker, LC3, increase and there
      is activation of the redox-sensitive kinase p66(shc). Under conditions of OGD,
      CHIP relocalizes from the cytosol to mitochondria. Mitochondria from CHIP KO mice
      have profound impairments in stress response induced by calcium overload,
      resulting in accelerated permeability transition activity. While CHIP-deficient
      neurons are morphologically intact, they are more susceptible to OGD consistent
      with a previously unknown neuroprotective role for CHIP in maintaining
      mitochondrial homeostasis. INNOVATION: CHIP relocalization to the mitochondria is
      essential for the regulation of mitochondrial integrity and neuronal survival
      following OGD. CONCLUSIONS: CHIP is an essential regulator of neuronal
      bioenergetics and redox tone. Altering the expression of this protein has
      profound effects on neuronal survival when cells are exposed to OGD.

PMID- 25602370
TI  - Influence of model boundary conditions on blood flow patterns in a patient
      specific stenotic right coronary artery.
AB  - BACKGROUND: In literature, the effect of the inflow boundary condition was
      investigated by examining the impact of the waveform and the shape of the spatial
      profile of the inlet velocity on the cardiac hemodynamics. However, not much work
      has been reported on comparing the effect of the different combinations of the
      inlet/outlet boundary conditions on the quantification of the pressure field and
      flow distribution patterns in stenotic right coronary arteries. METHOD: Non
      Newtonian models were used to simulate blood flow in a patient-specific stenotic
      right coronary artery and investigate the influence of different boundary
      conditions on the phasic variation and the spatial distribution patterns of blood
      flow. The 3D geometry of a diseased artery segment was reconstructed from a
      series of IVUS slices. Five different combinations of the inlet and the outlet
      boundary conditions were tested and compared. RESULTS: The temporal distribution
      patterns and the magnitudes of the velocity, the wall shear stress (WSS), the
      pressure, the pressure drop (PD), and the spatial gradient of wall pressure (WPG)
      were different when boundary conditions were imposed using different
      pressure/velocity combinations at inlet/outlet. The maximum velocity magnitude in
      a cardiac cycle at the center of the inlet from models with imposed inlet
      pressure conditions was about 29% lower than that from models using fully
      developed inlet velocity data. Due to the fact that models with imposed pressure
      conditions led to blunt velocity profile, the maximum wall shear stress at inlet
      in a cardiac cycle from models with imposed inlet pressure conditions was about
      29% higher than that from models with imposed inlet velocity boundary conditions.
      When the inlet boundary was imposed by a velocity waveform, the models with
      different outlet boundary conditions resulted in different temporal distribution
      patterns and magnitudes of the phasic variation of pressure. On the other hand,
      the type of different boundary conditions imposed at the inlet and the outlet did
      not have significant effect on the spatial distribution patterns of the PD, the
      WPG and the WSS on the lumen surface, regarding the locations of the maximum and
      the minimum of each quantity. CONCLUSIONS: The observations from this study
      indicated that the ways how pressure and velocity boundary conditions are imposed
      in computational models have considerable impact on flow velocity and shear
      stress predictions. Accuracy of in vivo measurements of blood pressure and
      velocity is of great importance for reliable model predictions.

PMID- 25602373
TI  - With appreciation and expectation.

PMID- 25602375
TI  - Clinical and biochemical tear lipid parameters in contact lens wearers.
AB  - PURPOSE: Alterations in tear film lipids may be important in modulating
      discomfort during contact lens wear. This study investigates associations between
      clinical and biological components of the lipid layer and seeks to determine the
      effect of lipid supplementation on contact lens wear comfort. METHODS:
      Participants were grouped into symptomatic (n = 10) and asymptomatic (n = 10)
      contact lens wearers according to the Contact Lens Dry Eye Questionnaire. After 6
      hours of lens wear, noninvasive surface drying time (NISDT) and the lipid layer
      grade were assessed using a Tearscope. Basal tears were collected using a
      microcapillary tube and assayed for concentration and activity of the secretory
      phospholipase A2 enzyme and concentration of the lipid aldehyde malondialdehyde.
      Mass spectrometry was used to characterize the tear lipidome. In the second
      phase, a liposomal spray (Tears Again, BioRevive) or a saline spray was sprayed
      over the upper eyelids of each subject during their down gaze and during lens
      wear. Noninvasive surface drying time and ocular comfort were obtained soon after
      spraying and again at 2 and 6 hours after the initial spray. Statistical tests
      included the Student t test, repeated-measures analysis of variance, and the
      Pearson correlation test where appropriate. RESULTS: Noninvasive surface drying
      time was lower (p = 0.01) in symptomatic (4.5 +/- 0.6 seconds) than in
      asymptomatic (9.9 +/- 3.1 seconds) contact lens wearers. The mole percentage of
      wax esters in the total lipidome increased with NISDT (R = 0.70, p = 0.01).
      Secretory phospholipase A2 enzyme activity in tears was associated with higher
      levels of malondialdehyde (R = 0.65, p = 0.01) and shorter NISDT (R = 0.84, p =
      0.001). Noninvasive surface drying time reduced over the time course for the
      saline spray (p = 0.01) but did not reduce until the 6-hour time point with the
      liposomal spray. With liposomal spray, NISDT was higher (p = 0.03) immediately
      after instillation compared with 6 hours later (9.5 +/- 1.9 vs. 5.2 +/- 2.1
      seconds). A longer NISDT was associated with improved ocular comfort for those
      using the liposomal spray (R = 0.25, p = 0.005) but not with saline. CONCLUSIONS:
      Degraded lipids and a lower mole percentage of wax esters in the tear film may be
      associated with a lower NISDT. Lipid supplements may improve ocular comfort
      during lens wear by increasing NISDT.

PMID- 25602372
TI  - The standard scrapie cell assay: development, utility and prospects.
AB  - Prion diseases are a family of fatal neurodegenerative diseases that involve the
      misfolding of a host protein, PrPC. Measuring prion infectivity is necessary for
      determining efficacy of a treatment or infectivity of a prion purification
      procedure; animal bioassays are, however, very expensive and time consuming. The
      Standard Scrapie Cell Assay (SSCA) provides an alternative approach. The SSCA
      facilitates quantitative in vitro analysis of prion strains, titres and
      biological properties. Given its robust nature and potential for high throughput,
      the SSCA has substantial utility for in vitro characterization of prions and can
      be deployed in a number of settings. Here we provide an overview on establishing
      the SSCA, its use in studies of disease dissemination and pathogenesis, potential
      pitfalls and a number of remaining challenges. 

PMID- 25602381
TI  - An implantable active-targeting micelle-in-nanofiber device for efficient and
      safe cancer therapy.
AB  - Nanocarriers have attracted broad attention in cancer therapy because of their
      ability to carry drugs preferentially into cancer tissue, but their application
      is still limited due to the systemic toxicity and low delivery efficacy of
      intravenously delivered chemotherapeutics. In this study, we develop a localized
      drug delivery device with combination of an active-targeting micellar system and
      implantable polymeric nanofibers. This device is achieved first by the formation
      of hydrophobic doxorubicin (Dox)-encapsulated active-targeting micelles assembled
      from a folate-conjugated PCL-PEG copolymer. Then, fabrication of the core-shell
      polymeric nanofibers is achieved with coaxial electrospinning in which the core
      region consists of a mixture of poly(vinyl alcohol) and the micelles and the
      outer shell layer consists of cross-linked gelatin. In contrast to the systematic
      administration of therapeutics via repeatedly intravenous injections of micelles,
      this implantable device has these capacities of greatly reducing the drug dose,
      the frequency of administration and side effect of chemotherapeutic agents while
      maintaining highly therapeutic efficacy against artificial solid tumors. This
      micelle-based nanofiber device can be developed toward the next generation of
      nanomedicine for efficient and safe cancer therapy. 

PMID- 25602383
TI  - Reversing a block on nerve growth.

PMID- 25602384
TI  - Pinpointing the neurons that signal hunger in mice.

PMID- 25602386
TI  - Toward a better understanding of tau.

PMID- 25602379
TI  - Development of genetic markers in Eucalyptus species by target enrichment and
      exome sequencing.
AB  - The advent of next-generation sequencing has facilitated large-scale discovery,
      validation and assessment of genetic markers for high density genotyping. The
      present study was undertaken to identify markers in genes supposedly related to
      wood property traits in three Eucalyptus species. Ninety four genes involved in
      xylogenesis were selected for hybridization probe based nuclear genomic DNA
      target enrichment and exome sequencing. Genomic DNA was isolated from the leaf
      tissues and used for on-array probe hybridization followed by Illumina
      sequencing. The raw sequence reads were trimmed and high-quality reads were
      mapped to the E. grandis reference sequence and the presence of single nucleotide
      variants (SNVs) and insertions/ deletions (InDels) were identified across the
      three species. The average read coverage was 216X and a total of 2294 SNVs and
      479 InDels were discovered in E. camaldulensis, 2383 SNVs and 518 InDels in E.
      tereticornis, and 1228 SNVs and 409 InDels in E. grandis. Additionally, SNV
      calling and InDel detection were conducted in pair-wise comparisons of E.
      tereticornis vs. E. grandis, E. camaldulensis vs. E. tereticornis and E.
      camaldulensis vs. E. grandis. This study presents an efficient and high
      throughput method on development of genetic markers for family- based QTL and
      association analysis in Eucalyptus. 

PMID- 25602387
TI  - Telomerase limits damage after heart attack.

PMID- 25602389
TI  - 65th AALAS National Meeting.

PMID- 25602390
TI  - Marsupials that model melanoma.

PMID- 25602391
TI  - FOIA in your state.

PMID- 25602392
TI  - Protocol amendment for an unrelated study.

PMID- 25602393
TI  - Response to protocol review scenario: IACUC should vote.

PMID- 25602394
TI  - Response to protocol review scenario: submit a new proposal.

PMID- 25602396
TI  - The presence and management of contaminants in non-certified, agriculturally
      sourced food items used as enrichment for laboratory animals.
AB  - One enrichment strategy for laboratory animals is the provision of food variety
      and foraging opportunities. Fresh agricultural items, including produce or
      packaged human food items, provide variation in palatability, texture and
      complexity and can therefore be used as enrichment for lab animals. But concerns
      are often raised that these food items might sometimes carry contaminants that
      could affect research subjects and confound experimental results. The author
      discusses the potential for agriculturally sourced foods used as enrichment for
      lab animals to be contaminated with mycotoxins, microorganisms and pesticide
      residues and the effects these contaminants might have on lab animals. He also
      suggests strategies for reducing the risk of contamination. 

PMID- 25602398
TI  - Humane endpoints for animals used in training.

PMID- 25602399
TI  - A future in zebrafish.

PMID- 25602397
TI  - Effects of experimental housing conditions on recovery of laboratory mice.
AB  - The beneficial effects of environment and social support during disease recovery
      in humans are widely accepted. Because laboratory mice are social animals and are
      highly motivated to interact with each other and with their environment, it is
      very likely that environmental and social factors are also beneficial to their
      recovery from experimental interventions or spontaneous diseases. The beneficial
      effects of enriched environments have been particularly well analyzed in the
      field of brain disorders, but several studies suggest that positive social
      contact and a complex and familiar environment may also support recovery from
      injury, from invasive procedures such as surgery or from spontaneously occurring
      diseases. The author reviews relevant publications on the effects of environment
      and social housing on recovery from disease or surgery in laboratory mice and
      other rodents. She concludes that in addition to promoting animal welfare,
      provision of optimal experimental housing conditions might also contribute to the
      clinical relevance of preclinical animal models by more closely simulating the
      environmental and social characteristics of disease recovery in humans. 

PMID- 25602400
TI  - Therapist characteristics and their effect on training outcomes: what counts?
AB  - BACKGROUND: Evidence exists for a relationship between individual characteristics
      and both job and training performance; however relationships may not be
      generalizable. Little is known about the impact of therapist characteristics on
      performance in postgraduate therapist training programmes. AIMS: The aim of this
      study was to investigate associations between the grades of trainee Low-Intensity
      and High-Intensity cognitive behavioural therapists and individual
      characteristics. METHOD: Trainee Low-Intensity (n = 81) and High-Intensity (n =
      59) therapists completed measures of personality and cognitive ability;
      demographic and course grade data for participants were collected. RESULTS:
      Degree classification emerged as the only variable to be significantly associated
      with performance across assessments and courses. Higher undergraduate degree
      classifications were associated with superior academic and clinical performance.
      Agreeableness was the only dimension of personality to be associated (positively)
      with clinical skill. Age was weakly and negatively associated with performance.
      CONCLUSIONS: Relationships between individual characteristics and training
      outcomes are complex and may be context specific. These results could have
      important implications for the selection and development of therapists for Low or
      High-Intensity cognitive behavioural therapy (CBT) training.

PMID- 25602401
TI  - Science, policy, and management of irrigation-induced selenium contamination in
      california.
AB  - Selenium was recognized as an important aquatic contaminant following the
      identification of widespread deformities in waterfowl at the agricultural
      drainage evaporation ponds of the Kesterson Reservoir (California) in 1983. Since
      then, California has been the focal point for global research and management of
      Se contamination. We analyzed the history and current developments in science,
      policy, and management of irrigation-induced Se contamination in California. In
      terms of management, we evaluated the effects of improvements in the design of
      local attenuation methods (drainage reuse and evaporation ponds) in conjunction
      with the development of programs for Se load reductions at the regional scale
      (namely the Grassland Bypass Project). In terms of policy, the USEPA is currently
      working on site-specific water quality criteria for the San Francisco Bay Delta
      that may be a landmark for future legislation on Se in natural water bodies. We
      provide a critical analysis of this approach and discuss challenges and
      opportunities in expanding it to other locations such as the Salton Sea.
      Management lessons learned in California and the novel policy approach may help
      prevent future events of Se contamination. 

PMID- 25602402
TI  - Volatilization of pesticides from golf courses in the United States: mass fluxes
      and inhalation health risks.
AB  - Golfers may be subject to chronic health risks from inhalation of vapors from
      pesticides applied to turf surfaces. The objective of this study was to provide a
      comprehensive evaluation of the volatilization potential of pesticides used on
      golf courses in the United States and to assess the resulting inhalation health
      risks. Long-term exposures were simulated using a fate and transport model for
      inhaled concentrations. The model was tested using data from field experiments
      for eight pesticides. Mean concentrations were overestimated by a factor of two,
      and the model explained 82% of observed variations. The model was subsequently
      used to estimate volatilization mass fluxes and air concentrations for 37
      chemicals using weather information from nine climatic zones in the United
      States. Simulation results indicated substantial regional variations in
      volatilization fluxes, concentrations, and health risks, largely due to weather
      and pesticide application variations. Hazard quotients associated with chronic
      noncarcinogenic health risks were found to be less than 10 for all chemicals and
      locations. Similarly, carcinogenic health risks for the 10 pesticides considered
      likely or possible carcinogens were determined to be less than 10. Based on
      currently available levels of chronic toxicity endpoints for human health
      (chronic reference doses and cancer potency factors), we could find no evidence
      of health risk to golfers from inhalation of these 37 pesticides. 

PMID- 25602403
TI  - Optimal fertilizer nitrogen rates and yield-scaled global warming potential in
      drill seeded rice.
AB  - Drill seeded rice ( L.) is the dominant rice cultivation practice in the United
      States. Although drill seeded systems can lead to significant CH and NO emissions
      due to anaerobic and aerobic soil conditions, the relationship between high
      yielding management practices, particularly fertilizer N management, and total
      global warming potential (GWP) remains unclear. We conducted three field
      experiments in California and Arkansas to test the hypothesis that by optimizing
      grain yield through N management, the lowest yield-scaled global warming
      potential (GWP = GWP Mg grain) is achieved. Each growing season, urea was applied
      at rates ranging from 0 to 224 kg N ha before the permanent flood. Emissions of
      CH and NO were measured daily to weekly during growing seasons and fallow
      periods. Annual CH emissions ranged from 9.3 to 193 kg CH-C ha yr across sites,
      and annual NO emissions averaged 1.3 kg NO-N ha yr. Relative to NO emissions, CH
      dominated growing season (82%) and annual (68%) GWP. The impacts of fertilizer N
      rates on GHG fluxes were confined to the growing season, with increasing N rate
      having little effect on CH emissions but contributing to greater NO emissions
      during nonflooded periods. The fallow period contributed between 7 and 39% of
      annual GWP across sites years. This finding illustrates the need to include
      fallow period measurements in annual emissions estimates. Growing season GWP
      ranged from 130 to 686 kg CO eq Mg season across sites and years. Fertilizer N
      rate had no significant effect on GWP; therefore, achieving the highest
      productivity is not at the cost of higher GWP. 

PMID- 25602404
TI  - Ammonia volatilization and nitrogen retention: how deep to incorporate urea?
AB  - Incorporation of urea decreases ammonia (NH) volatilization, but field
      measurements are needed to better quantify the impact of placement depth. In this
      study, we measured the volatilization losses after banding of urea at depths of
      0, 2.5, 5, 7.5, and 10 cm in a slightly acidic (pH 6) silt loam soil using wind
      tunnels. Mineral nitrogen (N) concentration and pH were measured in the top 2 cm
      of soil to determine the extent of urea N migration and the influence of
      placement depth on the availability of ammoniacal N for volatilization near the
      soil surface. Ammonia volatilization losses were 50% of applied N when urea was
      banded at the surface, and incorporation of the band decreased emissions by an
      average of 7% cm (14% cm when expressed as a percentage of losses after surface
      banding). Incorporating urea at depths >7.5 cm therefore resulted in negligible
      NH emissions and maximum N retention. Cumulative losses increased exponentially
      with increasing maximum NH-N and pH values measured in the surface soil during
      the experiment. However, temporal variations in these soil properties were poorly
      related to the temporal variations in NH emission rates, likely as a result of
      interactions with other factors (e.g., water content and NH-N adsorption) on, and
      fixation by, soil particles. Laboratory and field volatilization data from the
      literature were summarized and used to determine a relationship between NH losses
      and depth of urea incorporation. When emissions were expressed as a percentage of
      losses for a surface application, the mean reduction after urea incorporation was
      approximately 12.5% cm. Although we agree that the efficiency of urea
      incorporation to reduce NH losses varies depending on several soil properties,
      management practices, and climatic conditions, we propose that this value
      represents an estimate of the mean impact of incorporation depth that could be
      used when site-specific information is unavailable. 

PMID- 25602405
TI  - Large-chamber methane and nitrous oxide measurements are comparable to the
      backward lagrangian stochastic method.
AB  - Measurement of individual emission sources (e.g., animals or pen manure) within
      intensive livestock enterprises is necessary to test emission calculation
      protocols and to identify targets for decreased emissions. In this study, a
      vented, fabric-covered large chamber (4.5 * 4.5 m, 1.5 m high; encompassing
      greater spatial variability than a smaller chamber) in combination with on-line
      analysis (nitrous oxide [NO] and methane [CH] via Fourier Transform Infrared
      Spectroscopy; 1 analysis min) was tested as a means to isolate and measure
      emissions from beef feedlot pen manure sources. An exponential model relating
      chamber concentrations to ambient gas concentrations, air exchange (e.g., due to
      poor sealing with the surface; model linear when ~ 0 m s), and chamber dimensions
      allowed data to be fitted with high confidence. Alternating manure source
      emission measurements using the large-chamber and the backward Lagrangian
      stochastic (bLS) technique (5-mo period; bLS validated via tracer gas release,
      recovery 94-104%) produced comparable NO and CH emission values (no significant
      difference at < 0.05). Greater precision of individual measurements was achieved
      via the large chamber than for the bLS (mean +/- standard error of variance
      components: bLS half-hour measurements, 99.5 +/- 325 MUg CH s and 9.26 +/- 20.6
      MUg NO s; large-chamber measurements, 99.6 +/- 64.2 MUg CH s and 8.18 +/- 0.3 MUg
      NO s). The large-chamber design is suitable for measurement of emissions from
      manure on pen surfaces, isolating these emissions from surrounding emission
      sources, including enteric emissions. 

PMID- 25602406
TI  - Reduction of methyl isothiocyanate atmospheric emissions after application of
      metam sodium by shank injection.
AB  - Regulatory initiatives in the United States have created the impetus to reassess
      application methods for metam sodium (sodium -methyldithiocarbamate), a methyl
      isothiocyanate (MITC) generator, to reduce flux to the atmosphere. This paper
      compares flux rates in the years 1990 through 2002 with flux rates based on four
      studies conducted during the period 2008 through 2010 in California, Michigan,
      Wisconsin, and Washington using current shank-injection/compaction methods. Up to
      a 100-fold reduction in peak flux rates and total loss of MITC have been
      observed. A combination of the following factors led to these reductions in flux:
      soil moisture goals set at 70% of the field water holding capacity; improved
      design of shank-injection systems to break up the voids after injection;
      effective shank compaction to further reduce volatilization; and the use of water
      sealing, where applicable. These refinements in the application methods for metam
      sodium provide a means to merge environmental and agricultural goals in the
      United States and in other countries that use metam sodium. This paper documents
      the reduced atmospheric emissions of MITC under commercial production conditions
      when applied using good agricultural practices. This research also shows that
      MITC flux can be effectively managed without the use of high barrier tarp
      material. 

PMID- 25602407
TI  - Controlled-release urea commingled with rice seeds reduced emission of ammonia
      and nitrous oxide in rice paddy soil.
AB  - Reduction of ammonia (NH) and nitrous oxide (NO) emission and enhanced nitrogen
      (N) fertilizer use efficiency have been investigated with different N fertilizer
      management and application methods for irrigated rice production. Few studies
      have examined NH and NO emissions from rice paddy soil when commingling
      controlled release urea with rice seeds. The objective of this study was to
      assess NH volatilization and NO emission from a novel controlled-release urea
      formulation (CRU-180) when commingled at the full application rate with seeds in
      a single application during the preparation of plant plugs at the nursery stage.
      The experiment was conducted as a factorial design with two fertilizer sources
      (conventional urea and CRU-180), four rates (0, 100, 200, and 300 kg N ha), and
      three replicates. The entire amount of CRU-180 was incorporated into each plug
      with germinated seed. The conventional urea was split into four applications
      based on the standard practice for fertilizer application. The CRU-180 treatments
      reduced the NH and NO concentration in the paddy flood water and paddy soil
      solution as compared with the conventional urea treatments. The percentage of
      applied N fertilizer emitted as NH volatilization and NO emission in the CRU-180
      treatments was only about 10% of that from the conventional urea treatments at
      the same N application rate. The application of CRU-180 with seeds offers a novel
      N fertilizer management technique, a method to reduce environmental impacts
      associated with rice production and the cost of rice production. 

PMID- 25602409
TI  - Three-dimensional lake water quality modeling: sensitivity and uncertainty
      analyses.
AB  - Two sensitivity and uncertainty analysis methods are applied to a three
      dimensional coupled hydrodynamic-ecological model (ELCOM-CAEDYM) of a
      morphologically complex lake. The primary goals of the analyses are to increase
      confidence in the model predictions, identify influential model parameters,
      quantify the uncertainty of model prediction, and explore the spatial and
      temporal variabilities of model predictions. The influence of model parameters on
      four model-predicted variables (model output) and the contributions of each of
      the model-predicted variables to the total variations in model output are
      presented. The contributions of predicted water temperature, dissolved oxygen,
      total phosphorus, and algal biomass contributed 3, 13, 26, and 58% of total model
      output variance, respectively. The fraction of variance resulting from model
      parameter uncertainty was calculated by two methods and used for evaluation and
      ranking of the most influential model parameters. Nine out of the top 10
      parameters identified by each method agreed, but their ranks were different.
      Spatial and temporal changes of model uncertainty were investigated and
      visualized. Model uncertainty appeared to be concentrated around specific water
      depths and dates that corresponded to significant storm events. The results
      suggest that spatial and temporal variations in the predicted water quality
      variables are sensitive to the hydrodynamics of physical perturbations such as
      those caused by stream inflows generated by storm events. The sensitivity and
      uncertainty analyses identified the mineralization of dissolved organic carbon,
      sediment phosphorus release rate, algal metabolic loss rate, internal phosphorus
      concentration, and phosphorus uptake rate as the most influential model
      parameters. 

PMID- 25602408
TI  - Hydrogen Sulfide Emissions from Sow Farm Lagoons across Climates Zones.
AB  - Hydrogen sulfide (HS) emissions were measured periodically over the course of 2
      yr at three sow waste lagoons representing humid mesothermal (North Carolina,
      NC), humid microthermal (Indiana, IN), and semiarid (Oklahoma, OK) climates.
      Emissions were determined using a backward Lagrangian stochastic model in
      conjunction with line-sampled HS concentrations and measured turbulence. The
      median annual sow-specific (area-specific) lagoon emissions at the OK farm were
      approximately 1.6 g head [hd] d (5880 ug m s), whereas those at the IN and NC sow
      farms were 0.035 g hd d (130 ug m s), and 0.041 g hd d (260 ug m s),
      respectively. Hydrogen sulfide emissions generally increased with wind speed. The
      daily HS emissions from the OK lagoon were greatest during the first half of the
      year and decreased as the year progressed. Emissions were episodic at the NC and
      IN lagoons. The generally low emissions at the NC and IN lagoons were probably a
      result of significant populations of purple sulfur bacteria maintained in the
      humid mesothermal and humid microthermal climates. Most of the large HS emission
      events at the NC and IN lagoons appeared to be a result of either precipitation
      events or liquid pump-out events. The high emissions at the OK lagoon in a
      semiarid climate were largely a result of high wind speeds enhancing both lagoon
      and air boundary layer mixing. The climate (air temperature, winds, and
      precipitation) appeared to influence the HS emissions from lagoons. 

PMID- 25602410
TI  - Evaluation of the hooghoudt and kirkham tile drain equations in the soil and
      water assessment tool to simulate tile flow and nitrate-nitrogen.
AB  - Subsurface tile drains in agricultural systems of the midwestern United States
      are a major contributor of nitrate-N (NO-N) loadings to hypoxic conditions in the
      Gulf of Mexico. Hydrologic and water quality models, such as the Soil and Water
      Assessment Tool, are widely used to simulate tile drainage systems. The Hooghoudt
      and Kirkham tile drain equations in the Soil and Water Assessment Tool have not
      been rigorously tested for predicting tile flow and the corresponding NO-N
      losses. In this study, long-term (1983-1996) monitoring plot data from southern
      Minnesota were used to evaluate the SWAT version 2009 revision 531 (hereafter
      referred to as SWAT) model for accurately estimating subsurface tile drain flows
      and associated NO-N losses. A retention parameter adjustment factor was
      incorporated to account for the effects of tile drainage and slope changes on the
      computation of surface runoff using the curve number method (hereafter referred
      to as Revised SWAT). The SWAT and Revised SWAT models were calibrated and
      validated for tile flow and associated NO-N losses. Results indicated that, on
      average, Revised SWAT predicted monthly tile flow and associated NO-N losses
      better than SWAT by 48 and 28%, respectively. For the calibration period, the
      Revised SWAT model simulated tile flow and NO-N losses within 4 and 1% of the
      observed data, respectively. For the validation period, it simulated tile flow
      and NO-N losses within 8 and 2%, respectively, of the observed values. Therefore,
      the Revised SWAT model is expected to provide more accurate simulation of the
      effectiveness of tile drainage and NO-N management practices. 

PMID- 25602411
TI  - Pesticide and Nitrate Trends in Domestic Wells where Pesticide Use Is Regulated
      in Fresno and Tulare Counties, California.
AB  - The California Department of Pesticide Regulation initiated regulations on
      pesticide use in 1989 to mitigate groundwater contamination by atrazine [6-chloro
      -ethyl-'-(1-methylethyl)-1,3,5-triazine-2,4-diamine] and subsequently for
      simazine (6-chloro-,'-diethyl-1,3,5-triazine-2,4-diamine), diuron ['-(3,4
      dichlorophenyl)-,-dimethylurea], bromacil [5-bromo-6-methyl-3-(1-methylpropyl)
      2,4(1,3)-pyrimidinedione], and norflurazon [4-chloro-5-(methylamino)-2-[3
      (trifluoromethyl)phenyl]-3(2)-pyridazinone]. Annual water samples from 2000 to
      2012 were obtained from domestic wells in Fresno and Tulare counties in regulated
      areas designated either as leaching groundwater protection areas (GWPAs), where
      residues move downward in percolating water, or runoff GWPAs, where residues move
      offsite in rain or irrigation runoff water to sensitive sites such drainage
      wells. Concentrations decreased below the reporting limit, so maximum likelihood
      estimation methodology for left-censored data was used. Decreasing trends in
      concentration were measured in both GWPA designations for simazine, its breakdown
      products desisopropyl atrazine (ACET, 2-amino-4-chloro-6-ethylamino--triazine)
      and diamino chlorotriazine (DACT, 2,4-diamino-6-chloro--triazine), and diuron.
      Bromacil crop use was predominant in runoff GWPAs, where decreases over time were
      also measured. In contrast, increased trends were observed for norflurazon and
      its breakdown product desmethyl norflurazon [DMN, 4-chloro-5(amino)-2
      (alpha,alpha,alpha trifluorometa-tolyl] in runoff GWPAs. Use of simazine, diuron,
      and bromacil was regulated before norflurazon, so patterns of detection represent
      a shift to use of unregulated products. For NO, 22 of 67 wells indicated linear
      decreases in concentration coinciding with decreases in pesticide residues in
      those wells. Concentration of ACET, DACT, diuron, and NO in well water was two to
      five times greater when located in runoff GWPAs. Greater amounts of herbicide
      were applied to crops grown in runoff GWPAs, but high concentrations in runoff
      water entering ponds or drainage wells could also be a factor for increased well
      water concentration. Initial regulatory measures appear to have been effective in
      reducing groundwater concentrations, but continued monitoring is needed to
      evaluate changes made to the regulatory approach in 2004. 

PMID- 25602412
TI  - Heavy Metal Contamination and Assessment of Roadside and Foliar Dust along the
      Outer-Ring Highway of Shanghai, China.
AB  - Foliar and roadside dust samples were collected from five sites along the outer
      ring highway of Shanghai, one of the biggest metropolitan areas of China, to
      assess heavy/toxic metal contamination. Concentrations of Zn, Cu, Ni, As, and Hg
      in foliar dust were higher than in roadside dust, whereas concentrations of Pb
      and Cd were higher in roadside dust. In the roadside dust, average concentrations
      of all metals except As in foliar and roadside dust samples were significantly
      above the background values of soil in Shanghai: the ratios between the average
      of samples and background values of Shanghai were in the order: Cd (25.1) > Zn
      (12.2) > Cu (6.16) > Pb (5.74) > Ni (5.50) > Hg (5.18) > As (1.05). By using the
      geo-accumulation index, the pollution grades of seven heavy metals at five
      sampling sites were calculated. Roadside dust was heavily to extremely
      contaminated with Cd; moderately to heavily contaminated with Zn; and moderately
      contaminated with Cu, Hg, Pb, and Ni. Foliar dust was heavily contaminated with
      Cd; moderately to heavily contaminated with Zn and Cu; and moderately
      contaminated with Hg, Pb, and Ni. The contamination level of heavy metals in the
      Puxi area was greater than that in the Pudong area, which might be related to the
      industrial distribution and land use. Combined with correlation analysis,
      hierarchical cluster analysis indicated that atmospheric deposition is the main
      source of Cd, Hg, As, and Pb in dust and that Cu and Zn in dust are mainly from
      heavy traffic on the highway. A portion of Ni in dust also comes from the parent
      soil. 

PMID- 25602413
TI  - Arsenic removal from flowing irrigation water in bangladesh: impacts of channel
      properties.
AB  - Across Bangladesh, dry-season irrigation with arsenic-contaminated well water is
      loading arsenic onto rice paddies, leading to increased arsenic concentrations in
      plants, diminished crop yields, and increased human health risks. As irrigation
      water flows through conveyance channels between wells and rice fields, arsenic
      concentrations change over space and time, indicating that channels may provide a
      location for removing arsenic from solution. However, few studies have
      systematically evaluated the processes controlling arsenic concentrations in
      irrigation channels, limiting the ability to manipulate these systems and enhance
      arsenic removal from solution. The central goal of this study was to quantify how
      channel design affected removal of dissolved arsenic from flowing irrigation
      water. Field experiments were conducted in Bangladesh using a chemically constant
      source of arsenic-contaminated irrigation water and an array of constructed
      channels with varying geometries. The resulting hydraulic conditions affected the
      quantity of arsenic removed from solution within the channels by promoting known
      hydrogeochemical processes. Channels three times the width of control channels
      removed ~3 times the mass of arsenic over 32 min of flowing conditions, whereas
      negligible arsenic removal was observed in tarp-lined channels, which prevented
      soil-water contact. Arsenic removal from solution was ~7 times higher in a
      winding, 200-m-long channel than in the straight, 45-m-long control channels.
      Arsenic concentrations were governed by oxidative iron-arsenic coprecipitation
      within the water column, sorption to soils, and phosphate competition.
      Collectively, these results suggest that better design and management of
      irrigation channels may play a part in arsenic mitigation strategies for rice
      fields in Southern Asia. 

PMID- 25602414
TI  - Formation of Manganese Oxide Coatings onto Sand for Adsorption of Trace Metals
      from Groundwater.
AB  - Manganese oxide (MnO) occurs naturally in soil and has a high affinity for trace
      metals adsorption. In this work, we quantified the factors (pH; flow rate; use of
      oxidants such as bleach, HO, and O; initial Mn(II) concentrations; and two types
      of geologic media) affecting MnO coatings onto Ottawa and aquifer sand using
      batch and column experiments. The batch experiments consisted of manual and
      automated titration, and the column experiments mimicked natural MnO adsorption
      and oxidation cycles as a strategy for in situ adsorption. A Pb solution of 50 mg
      L was passed through MnO-coated sand at a flow rate of 4 mL min to determine its
      adsorption capacity. Batch experimental results showed that MnO coatings
      increased from pH 6 to 8, with maximum MnO coating occurring at pH 8. Regarding
      MnO coatings, bleach and O were highly effective compared with HO. The Ottawa
      sand had approximately twice the MnO coating of aquifer sand. The sequential
      increase in initial Mn(II) concentrations on both sands resulted in incremental
      buildup of MnO. The automated procedure enhanced MnO coatings by 3.5 times
      compared with manual batch experiments. Column results showed that MnO coatings
      were highly dependent on initial Mn(II) and oxidant concentrations, pH, flow
      rate, number of cycles (h), and the type of geologic media used. Manganese oxide
      coating exceeded 1700 mg kg for Ottawa sand and 130 mg kg for aquifer sand. The
      Pb adsorption exceeded 2200 mg kg for the Ottawa sand and 300 mg kg for the
      aquifer sand. 

PMID- 25602415
TI  - Determination of lead, cadmium, copper, and nickel in the tonghui river of
      beijing, china, by cloud point extraction-high resolution continuum source
      graphite furnace atomic absorption spectrometry.
AB  - Heavy metal contamination of water has become an important problem in recent
      years. Most hazardous heavy metals exist in environmental water in trace or ultra
      trace amounts, which requires establishing highly sensitive analytical methods.
      In this research, quantitative analyses were performed using high-resolution
      continuum source graphite furnace atomic absorption spectrometry combined with
      cloud point extraction (CPE) to determine Pb, Cd, Cu, and Ni levels in
      environmental surface water. By optimizing the CPE conditions, the enrichment
      factors were 29 for Pb, Cd, and Cu and 25 for Ni. The limits of detection (LOD)
      were 0.080, 0.010, 0.035, and 0.014 MUg L for Pb, Cd, Cu, and Ni, respectively.
      The sensitivity of the method is comparable with those reported in previous
      investigations using various methods and improves outcome by 2 to 3 orders of
      magnitude compared with the LODs of the current national standard methods of
      China. Our method was used to determine Pb, Cd, Cu, and Ni in 55 water samples
      collected from the Tonghui River, which is the principal river in the urban area
      of Beijing, China. The results indicated that the distributions of the four heavy
      metals in the Tonghui River were related with the environments. The levels of Pb
      and Ni exhibit increasing trends along the river from upstream to downstream
      possibly due to the existence of some chemical factories in the downstream area.
      Lead, Cd, Cu, and Ni averaged 13.9, 0.8, 46.8, and 38.5%, respectively, of the
      total amount of the determined heavy metals. The levels of the four heavy metals
      conformed to the Environmental Quality Standards for Surface Water (Grade I) of
      China. This work provides a reliable quantitative method to determine trace
      amount heavy metals in water, which lays a foundation for establishing standards
      and regulations for environmental water protection. 

PMID- 25602416
TI  - Complementary Phosphorus Speciation in Agricultural Soils by Sequential
      Fractionation, Solution P Nuclear Magnetic Resonance, and Phosphorus K-edge X-ray
      Absorption Near-Edge Structure Spectroscopy.
AB  - Ultisols in China need phosphorus (P) fertilization to sustain crop production
      but are prone to P loss in runoff. Balancing P inputs and loss requires detailed
      information about soil P forms because P speciation influences P cycling.
      Analytical methods vary in the information they provide on P speciation; thus, we
      used sequential fractionation (SF), solution P nuclear magnetic resonance (P
      NMR), and P K-edge X-ray absorption near-edge structure (XANES) spectroscopy to
      investigate organic P (P) and inorganic P (P) species in Chinese Ultisols managed
      for different crops and with different fertilizer inputs in the first study to
      combine these techniques to characterize soil P. Sequential fractionation showed
      that moderately labile NaOH-P was the largest P pool in these soils, P varied
      from 20 to 47%, and residual P ranged from 9 to 31%. Deoxyribonucleic acid (1-5%)
      and -inositol hexakisphosphate (-IHP, 4-10%) were the major P forms from P-NMR.
      Orthophosphate diesters determined by NMR were significantly correlated with
      labile NaHCO-P in SF ( > 0.981; < 0.001). Soil P was shown to be predominantly
      associated with iron and soluble calcium (Ca) by XANES. Furthermore, XANES
      identified hydroxyapatite in the soil receiving the highest rates of Ca-phosphate
      fertilizer, which had the highest HCl-P pool by SF, and also identified IHP (7%)
      in the soil with the highest proportion of -IHP from P-NMR. These results
      strongly suggest that a combined use of SF, solution P-NMR, and P K-edge XANES
      spectroscopy will provide the comprehensive information about soil P species
      needed for effective soil P management. 

PMID- 25602417
TI  - Evaluation of modified boehm titration methods for use with biochars.
AB  - The Boehm titration, originally developed to quantify organic functional groups
      of carbon blacks and activated carbons in discrete pK ranges, has received
      growing attention for analyzing biochar. However, properties that distinguish
      biochar from carbon black and activated carbon, including greater carbon
      solubility and higher ash content, may render the original Boehm titration method
      unreliable for use with biochars. Here we use seven biochars and one reference
      carbon black to evaluate three Boehm titration methods that use (i) acidification
      followed by sparging (sparge method), (ii) centrifugation after treatment with
      BaCl (barium method), and (iii) a solid-phase extraction cartridge followed by
      acidification and sparging (cartridge method) to remove carbonates and dissolved
      organic compounds (DOC) from the Boehm extracts before titration. Our results for
      the various combinations of Boehm reactants and methods indicate that no one
      method was free of bias for all three Boehm reactants and that the cartridge
      method showed evidence of bias for all pK ranges. By process of elimination, we
      found that a combination of the sparge method for quantifying functional groups
      in the lowest pK range (~5 to 6.4), and the barium method for quantifying
      functional groups in the higher pK ranges (~6.4 to 10.3 and ~10.3 to 13) to be
      free of evidence for bias. We caution, however, that further testing is needed
      and that all Boehm titration results for biochars should be considered suspect
      unless efforts were undertaken to remove ash and prevent interference from DOC. 

PMID- 25602418
TI  - Oxidative enzymes, the ultimate regulator: implications for factors affecting
      their efficiency.
AB  - Soil enzymes influence the distribution of organic matter (OM) and play a
      decisive role in the retention of OM in soil ecosystems. The present study was
      conducted to assess the role of oxidative and hydrolytic enzymes in OM
      decomposition under dry and submerged moisture conditions and to examine factors
      affecting their activity in Red and Brown soils. An incubation experiment of 6 mo
      duration was performed in a randomized complete block design with 10 treatments
      in triplicates. Rice straw (RS) and green manure (GM) were used at three rates
      (0, 5, and 25 mg g soil, expressed as control [CK], RS1, RS2, GM1, and GM2,
      respectively). The soils were maintained at two water levels: 25% (W1) and 200%
      (W2). All soil chemical properties and enzymatic activities were measured by
      standard methods. We found that the activities of soil phenol oxidase and
      catalase in the Brown soil were 2- and 1.5-fold higher than in the Red soil,
      respectively. This led to high OM decomposition, resulting in 1.23- and 1.2-fold
      higher carbon (C) and nitrogen (N) mineralization and 1.23- and 1.21-fold more
      dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) in the Brown
      soil. In contrast, low oxidative enzyme activities in the Red soil decreased C
      and N mineralization, DOC, DON, reducing sugars (2.58-fold), and amino acids
      (2.22-fold) but increased the phenolic compounds (1.36-fold). The hydrolytic
      enzymes (i.e., urease and neutral phosphatase) showed significant correlation ( <
      0.01) to amino acids and reducing sugars but showed no correlation to phenolic
      compounds and soil organic matter (SOM). Conversely, oxidative enzymes (i.e.,
      phenol oxidase and catalase) showed significant correlation ( < 0.01) to phenolic
      compounds, amino acids, reducing sugars, and SOM. Our results suggest that
      oxidative enzymes are key components of the pathways involved in the breakdown of
      organic compounds and OM in soils and consequently act as an "enzymatic latch."
      We observed that soil water and pH have significant ( < 0.01) effects on soil
      enzyme activity. 

PMID- 25602420
TI  - Soil carbon change and net energy associated with biofuel production on marginal
      lands: a regional modeling perspective.
AB  - The use of marginal lands for biofuel production has been proposed as a promising
      solution for meeting biofuel demands while avoiding food-feed-fuel conflicts.
      However, uncertainty surrounds whether marginal lands can be reliably located, as
      well as their inherent biofuel potential and the possible environmental impacts.
      We developed a quantitative approach that integrates high-resolution land cover
      and land productivity to classify productive croplands and nonarable marginal
      lands in a nine-county region in southern Michigan. The classified lands were
      then examined with the spatially explicit modeling framework using the
      Environmental Policy Integrated Climate (EPIC) model to estimate net energy (NE)
      and soil organic carbon (SOC) changes associated with the cultivation of
      different annual and perennial production systems. Simulation results suggest
      that biofuel production systems underperform on marginal lands when compared to
      productive croplands. However, we found perennial grasses could perform better
      than annual crops. Hence, when growing perennial bioenergy crops on marginal
      lands instead of productive croplands, less additional land (about 0.09 ha per
      each hectare planted) would be needed to achieve the same NE than if growing
      annual bioenergy crops (additional 0.17 ha per hectare planted). Miscanthus ( * )
      and switchgrass ( L.) can produce 112.43 and 74.61 GJ ha yr NE, respectively, and
      have the potential to sequester, on average, 0.59 and 0.23 Mg C ha yr SOC,
      respectively. Notably, simulation results indicate substantial variability of the
      NE and SOC storage potential across the study region. Thus, although perennial
      energy crops are promising options for biofuel production on marginal lands,
      given the large spatial variability, regional- and site-specific management
      strategies are required for sustainable biofuel production. 

PMID- 25602419
TI  - Fate of soil-applied olive mill wastewater and potential phytotoxicity assessed
      by two bioassay methods.
AB  - Controlled land spreading of untreated olive mill wastewater (OMW) has been
      widely practiced as a means of its disposal. However, potential phytotoxic
      effects are critical for the selection of sites and crop types and for proper
      synchronization between land application and cropping. This study traced the fate
      of dissolved organic carbon (DOC), total phenols (TP), electrical conductivity,
      pH, microbial counts, and phytotoxicity to cress ( L.) after soil application at
      doses equivalent to 80, 160, and 320 m ha. Vertisol (fine-clayey) and Loess
      (sandy loam) soils were treated and incubated at 12 or 25 degrees C and at
      moisture contents maintained at 70% of field water capacity or gradually reduced
      from 70 to 20% without compensation. Temperature, rather than moisture content,
      had a major effect on removal rates of DOC and TP. The maximum combined effect of
      warm temperature and higher moisture content resulted in removal rates greater
      than those under cooler, drier conditions by factors of up to 1.8 and 4.1 for DOC
      and TP, respectively. Favorable biodegradation conditions were indicated by
      increased numbers of total soil microorganisms and fungi by factors of up to 26
      and 5, respectively. A whole-soil bioassay was developed to assess the dynamics
      of residual soil phytotoxicity after OMW application. Phytotoxicity measurement
      in soil extract generally showed stronger inhibition or stimulation activity than
      measurement in whole soil, depending on soil type and OMW dose. The newly
      developed bioassay seems to be useful for the refinement of general
      recommendations regarding permitted OMW application doses. 

PMID- 25602421
TI  - The effect of coal-bed methane water on spearmint and peppermint.
AB  - Coal bed methane is extracted from underground coal seams that are flooded with
      water. To reduce the pressure and to release the methane, the water needs to be
      pumped out. The resulting waste water is known as coal bed methane water (CBMW).
      Major concerns with the use of CBMW are its high concentrations of S, Na,
      dissolved Ca, Mg, SO, and bicarbonate (HCO). Irrigation water is a scarce
      resource in most of the western states. The objective of this study was to
      evaluate the effect of various amounts of CBMW on the growth, essential oil
      content, composition, and antioxidant activity of spearmint ( L.) and peppermint
      ( L.) crops that were irrigated with the water. These two crops are grown in some
      western states and are potential specialty crops to Wyoming farmers. The
      irrigation treatments were 0% CBMW (tap water only), 25% CBMW (25% CBMW plus 75%
      tap water), 50% CBMW (50% CBMW and 50% tap water), 75% CBMW (75% CBMW plus 25%
      tap water), and 100% CBMW. Analyses of the data revealed that the CBMW treatments
      did not affect the antioxidant capacity of spearmint or peppermint oil (242 and
      377 MUmol L Trolox g, respectively) or their major oil constituents (carvone or
      menthol). Coal bed methane water at 100% increased total phenols and total
      flavonoids in spearmint but not in peppermint. Coal bed methane water also
      affected oil content in peppermint but not in spearmint. Spearmint and peppermint
      could be watered with CBMW at 50% without suppression of fresh herbage yields.
      However, CBMW at 75 and 100% reduced fresh herbage yields of both crops and oil
      yields of peppermint relative to the control. 

PMID- 25602422
TI  - Nitrate Concentration Trends in Iowa's Rivers, 1998 to 2012: What Challenges
      Await Nutrient Reduction Initiatives?
AB  - Nitrate-nitrogen (NO-N) concentrations threaten water supplies and contribute to
      impairments of surface water resources. In this study, we analyzed concentration
      trends at 60 ambient river monitoring sites in Iowa for the years 1998 to 2012 to
      assess the presence of linear trends in the NO-N concentration data using a time
      series method that accounted for temporal correlation and combined the trend
      information from individual sites into an assessment of the state-wide rate of
      change in river NO-N concentrations. Forty-six of the sites had sufficient
      records for trend analysis. Study results indicated that 37 out of 46 sites (80%)
      did not have statistically significant trends over the monitoring period ( >
      0.1). Six monitoring sites in western Iowa had statistically significant
      increasing trends ( < 0.05), and three additional sites located in western and
      southern Iowa showed nominally significant increasing trends ( < 0.1). The rate
      of statistically significant increases ranged from 0.15 to 0.33 mg L yr.
      Aggregated across the state, the overall trend of NO-N concentrations in Iowa
      rivers is increasing, with an average and median rate of 0.05 and 0.03 mg L yr,
      respectively. Increasing concentration is likely associated with increasing
      trends in fertilizer sales and animal production, but better tracking is needed
      to establish a definitive relation. Reducing NO-N concentrations using
      conservation practices is a major focus of the recently proposed Iowa Nutrient
      Reduction Strategy, and our study provides an important milestone preceding
      implementation of the strategy. 

PMID- 25602423
TI  - Effects of long-term poultry litter application on phosphorus soil chemistry and
      runoff water quality.
AB  - Continuous application of poultry litter (PL) significantly changes many soil
      properties, including soil test P (STP); Al, Fe, and Ca concentrations; and pH,
      which can affect the potential for P transport in surface runoff water. We
      conducted rainfall simulations on three historically acidic silt loam soils in
      Arkansas, Missouri, and Virginia to establish if long-term PL applications would
      affect soil inorganic P fractions and the resulting dissolved reactive P (DRP) in
      runoff water. Soil samples (0-5 cm depth) were taken to find sites ranging in
      Mehlich-3 STP from 20 to 1154 mg P kg. Simulated rainfall events were conducted
      on 3-m plots at 6.7 cm h, and runoff was collected for 30 min. Correlation
      between Mehlich-3 and runoff DRP indicated a linear relationship to 833 mg
      Mehlich-3 P kg. As Mehlich-3 STP increased, a concomitant increase in soil pH and
      Ca occurred on all soils. Soil P fractionation demonstrated that, as Mehlich-3
      STP generally increased above 450 mg P kg (from high to very high), the easily
      soluble and loosely bound P fractions decreased by 3 to 10%. Water-insoluble
      complexes of P bound to Al and Ca were the main drivers in the reduction of DRP
      in runoff, accounting for up to 43 and 38% of total P, respectively. Basing
      runoff DRP concentration projections solely on Mehlich-3 STP may overestimate
      runoff P losses from soils receiving long-term PL applications due to dissolution
      of water-insoluble Ca-P compounds. 

PMID- 25602424
TI  - Watershed Regressions for Pesticides (WARP) Models for Predicting Stream
      Concentrations of Multiple Pesticides.
AB  - Watershed Regressions for Pesticides for multiple pesticides (WARP-MP) are
      statistical models developed to predict concentration statistics for a wide range
      of pesticides in unmonitored streams. The WARP-MP models use the national
      atrazine WARP models in conjunction with an adjustment factor for each additional
      pesticide. The WARP-MP models perform best for pesticides with application timing
      and methods similar to those used with atrazine. For other pesticides, WARP-MP
      models tend to overpredict concentration statistics for the model development
      sites. For WARP and WARP-MP, the less-than-ideal sampling frequency for the model
      development sites leads to underestimation of the shorter-duration concentration;
      hence, the WARP models tend to underpredict 4- and 21-d maximum moving-average
      concentrations, with median errors ranging from 9 to 38% As a result of this
      sampling bias, pesticides that performed well with the model development sites
      are expected to have predictions that are biased low for these shorter-duration
      concentration statistics. The overprediction by WARP-MP apparent for some of the
      pesticides is variably offset by underestimation of the model development
      concentration statistics. Of the 112 pesticides used in the WARP-MP application
      to stream segments nationwide, 25 were predicted to have concentration statistics
      with a 50% or greater probability of exceeding one or more aquatic life
      benchmarks in one or more stream segments. Geographically, many of the modeled
      streams in the Corn Belt Region were predicted to have one or more pesticides
      that exceeded an aquatic life benchmark during 2009, indicating the potential
      vulnerability of streams in this region. 

PMID- 25602425
TI  - Effects of past copper contamination and soil structure on copper leaching from
      soil.
AB  - Copper contamination affects biological, chemical, and physical soil properties
      and associated ecological functions. Changes in soil pore organization as a
      result of Cu contamination can dramatically affect flow and contaminant transport
      in polluted soils. This study assessed the influence of soil structure on the
      movement of water and Cu in a long-term polluted soil. Undisturbed soil cores
      collected along a Cu gradient (from about 20 to about 3800 mg Cu kg soil) were
      scanned using X-ray computed tomography (CT). Leaching experiments were performed
      to analyze tracer transport, colloid leaching, and dissolved organic carbon (DOC)
      and Cu losses. The 5% arrival time () and apparent dispersivity (lambda) for
      tracer breakthrough were calculated by fitting the experimental data to a
      nonparametric, double-lognormal probability density function. Soil bulk density,
      which did not follow the Cu gradient, was the main driver of preferential flow,
      while macroporosity determined by X-ray CT (for pores >180 MUm) proved the best
      predictor of solute transport. Higher preferential flow due to the presence of
      well-aligned pores and small cracks controlled water movement in compacted soil.
      Transport of Cu was rapid during the first flush (~1 pore volume) in association
      with the movement of colloid particles, followed by slower transport in
      association with the movement of DOC in the soil solution. The relative amount of
      Cu released was strongly correlated with macroporosity as determined by X-ray CT,
      indicating the promising potential of this visualization technique for predicting
      contaminant transport through soil. 

PMID- 25602426
TI  - Phosphorus fractions in solid and liquid separates of Swine slurry separated
      using different technologies.
AB  - Solid-liquid separation is a manure management option whereby P-rich solid is
      separated from N-rich liquid, allowing the separated liquid to be used as a
      fertilizer without oversupplying P. Little information is available on how the
      different P fractions in manures are partitioned to solid and liquid during
      separation. We examined the distribution of various P fractions in liquid and
      solid separates of swine manure, separated using different techniques, to gain
      information useful for making choices regarding the optimum use of manure
      separates. Samples of raw manure (RM) and their separated solid (SS) and liquid
      (SL) were obtained using three different separation techniques: (i)
      centrifugation without flocculant (CNF), (ii) centrifugation with a flocculant
      (CFL), and (iii) rotary press with a flocculant (RFL). These were subsequently
      analyzed for P using a modified Hedley fractionation scheme. Only a small
      proportion of RM, ranging from 5 to 12%, was recovered in SS, an advantage if SS
      is to be transported off-site. Concentrations of molybdate-reactive P and total P
      in all P fractions were less in SL than in the corresponding RM on a fresh-weight
      basis. The separation index (percentage partitioned to SS) for total labile P
      (water-extractable + NaHCO-extractable P) was 63, 81, and 75% for CNF, CFL, and
      RFL, respectively. The proportion of total P in labile form was significantly
      lower in SL than in RM. Therefore, using SL as a fertilizer instead of RM may
      help to avoid excessive buildup of soil test P with manure applications. 

PMID- 25602427
TI  - Long-term crop and soil response to biosolids applications in dryland wheat.
AB  - Biosolids have the potential to improve degraded soils in grain-fallow rotations.
      Our objectives were to determine if repeated biosolids applications in wheat (
      L.)-fallow could supply adequate but not excessive N for grain production and
      increase soil C without creating a high risk of P loss. A replicated on-farm
      experiment was established in 1994 in central Washington, comparing anaerobically
      digested biosolids with anhydrous NH and a zero-N control. Biosolids were applied
      at 5, 7, and 9 Mg ha every fourth year through 2010 and incorporated 10 cm deep,
      while anhydrous NH plots received 56 kg ha N every second year. Grain yield and
      protein were determined. Soil chemical, biological, and bulk density analyses
      were made in 2012. Medium and high biosolids rates significantly increased grain
      yield (3.63 vs. 3.13 Mg ha) and protein (103 vs. 85 g kg) compared with anhydrous
      NH averaged across all crops. The medium biosolids rate had significantly lower
      bulk density (1.05 vs. 1.22 g kg) and greater total C (0-10-cm depth) (16.9 vs.
      9.4 g kg), mineralizable N (156 vs. 52 mg kg), and extractable P (114 vs. 16 mg
      kg) than anhydrous NH. The P index site vulnerability increased from low for
      anhydrous NH to medium for the biosolids treatments. Soil NO-N was nearly always
      <10 mg N kg soil (0-30-cm depth). Medium and high biosolids rates significantly
      increased bacteria/fungi ratios, Gram-negative bacteria, and anaerobic bacteria
      markers compared with anhydrous NH. Biosolids can be an agronomically and
      environmentally sound management practice in wheat-fallow systems. 

PMID- 25602428
TI  - Transport of Residual Nitrogen and Carbon through Intact Soil Cores Amended with
      Stockpiled Feedlot Manure with Wood-Chip or Straw Bedding.
AB  - The environmental impact of using wood chips instead of straw bedding with
      feedlot manure on transport and leaching potential from feedlot manure is
      unknown. Our main objective was to determine if transport of total N, total
      organic N, NO-N, and nonpurgeable organic C (NPOC) to subsurface soil was lower
      for soils amended with feedlot manure if combined with wood chips compared with
      straw. A secondary objective was to compare transport of N and NPOC with organic
      amendments versus inorganic fertilizer. Stockpiled feedlot manure (SM) with wood
      chip (SM-WD) or barley straw (SM-ST) bedding at 39 Mg (dry wt.) ha, and inorganic
      fertilizer (IN) at 100 kg N ha, was applied annually for 13 yr to a clay loam
      soil in a replicated field experiment in southern Alberta, Canada. Intact soil
      cores were taken in fall 2011 (0-30 cm depth) from the three treatments, and the
      residual N and NPOC were eluted from the soil cores. Total N, total organic N,
      and NPOC were determined on filtered (1.0 MUm) effluent samples that are
      primarily dissolved fraction but may contain some small particulate N and C. Peak
      concentrations, flow-weighted mean concentrations, and mass loss of total N,
      total organic N, NO-N, and NPOC were significantly ( <= 0.05) lower by 35 to 86%
      for SM-WD compared with SM-ST. Mean recoveries were also significantly lower for
      SM-WD than SM-ST by 0.07 to 8% (absolute difference). The transport behavior was
      similar for SM-WD and IN treatment, but solute transport was greater for SM-ST
      than for IN. Application of stockpiled feedlot manure with wood chips instead of
      straw bedding may be a beneficial management practice to reduce transport and
      leaching potential of N fractions and NPOC. 

PMID- 25602429
TI  - Mitigation of biocide and fungicide concentrations in flow-through vegetated
      stream mesocosms.
AB  - Organic chemicals entering surface waters may interact with aquatic macrophytes,
      which in turn may reduce potential negative effects on aquatic organisms. The
      overall objective of the present study was to determine the significance of
      aquatic macrophytes to the retention of organic chemicals in slow-flowing streams
      and thus their contribution to the mitigation of the risks that these compounds
      may pose to aquatic ecosystems. Hence, we conducted a study on the mitigation of
      the biocides triclosan and triclocarban and the fungicides imazalil,
      propiconazole and thiabendazole, which were experimentally spiked to five flow
      through stream mesocosms (45 m length, 0.4 m width, 0.26 m water depth, discharge
      1 L/s), four of which were planted with the submerged macrophyte (Planch.).
      Chemical analyses were performed using liquid chromatography-tandem mass
      spectrometry following solid-phase extraction for water samples and accelerated
      solvent extraction for macrophyte and sediment samples. The peak reductions of
      biocide and fungicide concentrations from the inlet to the outlet sampling sites
      were >=48% in all stream mesocosms, and the peak reductions in the vegetated
      stream mesocosms were 20 to 25% greater than in the unvegetated mesocosm. On
      average, 7 +/- 3 to 10 +/- 3% and 28 +/- 8 to 34 +/- 14% of the initially applied
      amount of fungicides and biocides, respectively, were retained by macrophytes.
      There was a significant correlation between retention by macrophytes and the
      lipophility of the compounds. 

PMID- 25602430
TI  - Addressing the fouling of in situ ultraviolet-visual spectrometers used to
      continuously monitor water quality in brackish tidal marsh waters.
AB  - The introduction of portable in situ ultraviolet-visual spectrometers has made
      possible the collection of water quality parameters at a high frequency in
      dynamic systems such as tidal marshes. The usefulness of this technology is
      inhibited by fouling of the instrument's optics. In this study, a spectrometer
      fitted with manufacturer-recommended compressed air optical cleaning was
      installed in a brackish marsh to determine if fouling interfered with
      measurements between bi-weekly servicing. During a 2-wk period, the absorbance
      measured in air at 220 nm increased from 9 to 549 m, indicating major fouling. An
      antifouling system was developed that reduced the time of exposure of the optics
      to stream water and used a pressurized fresh water cleaning. After implementation
      of the system, the absorbance in air increased to at most 63 m after 2 wk of data
      collection. The dramatic reduction in fouling will allow quality long-term data
      to be collected using this technology. 

PMID- 25602431
TI  - Turbidimetric determination of anionic polyacrylamide in low carbon soil
      extracts.
AB  - Concerns over runoff water quality from agricultural lands and construction sites
      have led to the development of improved erosion control practices, including
      application of polyacrylamide (PAM). We developed a quick and reliable method for
      quantifying PAM in soil extracts at low carbon content by using a turbidimetric
      reagent, Hyamine 1622. Three high-molecular weight anionic PAMs differing in
      charge density (7, 20, and 50 mol%) and five water matrices, deionized (DI) water
      and extracts from four different soils, were used to construct PAM calibration
      curves by reacting PAM solutions with hyamine and measuring turbidity development
      from the PAM-hyamine complex. The PAM calibration curve with DI water showed a
      strong linear relationship ( = 0.99), and the sensitivity (slope) of calibration
      curves increased with increasing PAM charge density with a detection limit of 0.4
      to 0.9 mg L. Identical tests with soil extracts showed the sensitivity of the
      hyamine method was dependent on the properties of the soil extract, primarily
      organic carbon concentration. Although the method was effective in mineral soils,
      the highest charge density PAM yielded a more reliable linear relationship ( >
      0.97) and lowest detection limit (0.3 to 1.2 mg L), compared with those of the
      lower charge density PAMs (0.7 to 23 mg L). Our results suggest that the hyamine
      test could be an efficient method for quantifying PAM in environmental soil water
      samples as long as the organic carbon in the sample is low, such as in subsurface
      soil material often exposed at construction sites. 

PMID- 25602432
TI  - Greening vermont: the search for a sustainable state.

PMID- 25602433
TI  - Soils and human health.

PMID- 25602434
TI  - Magnetic microbubble-mediated ultrasound-MRI registration based on robust optical
      flow model.
AB  - BACKGROUND: As a dual-modality contrast agent, magnetic microbubbles (MMBs) can
      not only improve contrast of ultrasound (US) image, but can also serve as a
      contrast agent of magnetic resonance image (MRI). With the help of MMBs, a new
      registration method between US image and MRI is presented. METHODS: In this
      method, MMBs were used in both ultrasound and magnetic resonance imaging process
      to enhance the most important information of interest. In order to reduce the
      influence of the speckle noise to registration, semi-automatic segmentations of
      US image and MRI were carried out by using active contour model. After that, a
      robust optical flow model between US image segmentation (floating image) and MRI
      segmentation (reference image) was built, and the vector flow field was estimated
      by using the Coarse-to-fine Gaussian pyramid and graduated non-convexity (GNC)
      schemes. RESULTS: Qualitative and quantitative analyses of multiple group
      comparison experiments showed that registration results using all methods tested
      in this paper without MMBs were unsatisfactory. On the contrary, the proposed
      method combined with MMBs led to the best registration results. CONCLUSION: The
      proposed algorithm combined with MMBs contends with larger deformation and
      performs well not only for local deformation but also for global deformation. The
      comparison experiments also demonstrated that ultrasound-MRI registration using
      the above-mentioned method might be a promising method for obtaining more
      accurate image information.

PMID- 25602435
TI  - Assembly of indoline-2-carboxylate-embodied dipeptides via Pd-catalyzed C(sp2)-H
      bond direct functionalization.
AB  - Intramolecular dehydrogenative cyclization of 2-methoxyiminoacyl-protected
      phenylalanine derivatives proceeded at 110  degrees C under catalysis of Pd(OAc)2
      in the presence of 1-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate to afford
      substituted indoline-2-carboxylates that were converted into indoline-2
      carboxylate-embodied dipeptides via Raney Ni-catalyzed hydrogenation. 

PMID- 25602436
TI  - Bortezomib inhibits gastric carcinoma HGC-27 cells through the phospho-Jun N
      terminal kinase (p-JNK) pathway in vitro.
AB  - The study is designed to explore the anticancer mechanism of Bortezomib. The
      effects of Bortezomib on the proliferation of human gastric cancer cells HGC-27
      and expression levels of the phospho-Jun N-terminal kinase (p-JNK) pathway
      related proteins in vitro were investigated. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay revealed that the Bortezomib
      significantly decreased the viability of HGC-27 cells and induced apoptosis.
      Western blot showed that the Bortezomib strongly increased the levels of p-JNK,
      caspase-3, PARP, and bax proteins while it increased the level of bcl-2. However,
      SP600125 can significantly decrease antitumour effects of Bortezomib in HGC-27
      cells. It can be concluded that Bortezomib has significant inhibitory effects on
      the growth of HGC-27 cells. The effect may be achieved partly via upregulating
      JNK pathway and its down-stream apoptosis-related proteins. Therefore, Bortezomib
      may be beneficial in gastric carcinoma treatment. 

PMID- 25602438
TI  - Avian Influenza in wild birds from Chile, 2007-2009.
AB  - Aquatic and migratory birds, the main reservoir hosts of avian influenza viruses
      including those with high pathogenic potential, are the wildlife species with the
      highest risk for viral dissemination across countries and continents. In 2002,
      the Chilean poultry industry was affected with a highly pathogenic avian
      influenza strain, which created economic loss and triggered the establishment of
      a surveillance program in wild birds. This effort consisted of periodic samplings
      of sick or suspicious animals found along the coast and analyses with
      standardized techniques for detection of influenza A virus. The aim of this work
      is to report the detection of three avian influenza strains (H13N2, H5N9, H13N9)
      in gulls from Chile between 2007-2009, which nucleotide sequences showed highest
      similitudes to viruses detected in wild birds from North America. These results
      suggest a dissemination route for influenza viruses along the coasts of Americas.
      Migratory and synanthropic behaviors of birds included in this study support
      continued monitoring of avian influenza viruses isolated from wild birds in The
      Americas and the establishment of biosecurity practices in farms. 

PMID- 25602437
TI  - Analysis of the initiation of nuclear pore assembly by ectopically targeting
      nucleoporins to chromatin.
AB  - Nuclear pore complexes (NPCs) form the gateway to the nucleus, mediating
      virtually all nucleocytoplasmic trafficking. Assembly of a nuclear pore complex
      requires the organization of many soluble sub-complexes into a final massive
      structure embedded in the nuclear envelope. By use of a LacI/LacO reporter
      system, we were able to assess nucleoporin (Nup) interactions, show that they
      occur with a high level of specificity, and identify nucleoporins sufficient for
      initiation of the complex process of NPC assembly in vivo. Eleven nucleoporins
      from different sub-complexes were fused to LacI-CFP and transfected separately
      into a human cell line containing a stably integrated LacO DNA array. The LacI
      Nup fusion proteins, which bound to the array, were examined for their ability to
      recruit endogenous nucleoporins to the intranuclear LacO site. Many could recruit
      nucleoporins of the same sub-complex and a number could also recruit other sub
      complexes. Strikingly, Nup133 and Nup107 of the Nup107/160 subcomplex and Nup153
      and Nup50 of the nuclear pore basket recruited a near full complement of
      nucleoporins to the LacO array. Furthermore, Nup133 and Nup153 efficiently
      targeted the LacO array to the nuclear periphery. Our data support a
      hierarchical, seeded assembly pathway and identify Nup133 and Nup153 as effective
      "seeds" for NPC assembly. In addition, we show that this system can be applied to
      functional studies of individual nucleoporin domains as well as to specific
      nucleoporin disease mutations. We find that the R391H cardiac arrhythmia/sudden
      death mutation of Nup155 prevents both its subcomplex assembly and nuclear rim
      targeting of the LacO array. 

PMID- 25602439
TI  - SVP-like MADS-box protein from Carya cathayensis forms higher-order complexes.
AB  - To properly regulate plant flowering time and construct floral pattern, MADS
      domain containing transcription factors must form multimers including homo- and
      hetero-dimers. They are also active in forming hetero-higher-order complexes with
      three to five different molecules. However, it is not well known if a MADS-box
      protein can also form homo-higher-order complex. In this study a biochemical
      approach is utilized to provide insight into the complex formation for an SVP
      like MADS-box protein cloned from hickory. The results indicated that the protein
      is a heterogeneous higher-order complex with the peak population containing over
      20 monomers. Y2H verified the protein to form homo-complex in yeast cells.
      Western blot of the hickory floral bud sample revealed that the protein exists in
      higher-order polymers in native. Deletion assays indicated that the flexible C
      terminal residues are mainly responsible for the higher-order polymer formation
      and the heterogeneity. Current results provide direct biochemical evidences for
      an active MADS-box protein to be a high order complex, much higher than a
      quartermeric polymer. Analysis suggests that a MADS-box subset may be able to
      self-assemble into large complexes, and thereby differentiate one subfamily from
      the other in a higher-order structural manner. Present result is a valuable
      supplement to the action of mechanism for MADS-box proteins in plant development.

PMID- 25602440
TI  - Severe drought stress is affecting selected primary metabolites, polyphenols, and
      volatile metabolites in grapevine leaves (Vitis vinifera cv. Pinot noir).
AB  - Extreme weather conditions with prolonged dry periods and high temperatures as
      well as heavy rain events can severely influence grapevine physiology and grape
      quality. The present study evaluates the effects of severe drought stress on
      selected primary metabolites, polyphenols and volatile metabolites in grapevine
      leaves. Among the 11 primary metabolites, 13 polyphenols and 95 volatiles which
      were analyzed, a significant discrimination between control and stressed plants
      of 7 primary metabolites, 11 polyphenols and 46 volatile metabolites was
      observed. As single parameters are usually not specific enough for the
      discrimination of control and stressed plants, an unsupervised (PCA) and a
      supervised (PLS-DA) multivariate approach were applied to combine results from
      different metabolic groups. In a first step a selection of five metabolites,
      namely citric acid, glyceric acid, ribose, phenylacetaldehyde and 2-methylbutanal
      were used to establish a calibration model using PLS regression to predict the
      leaf water potential. The model was strong enough to assign a high number of
      plants correctly with a correlation of 0.83. The PLS-DA provides an interesting
      approach to combine data sets and to provide tools for the specific evaluation of
      physiological plant stresses. 

PMID- 25602442
TI  - Diagnostic accuracies of procalcitonin and C-reactive protein for bacterial
      infection in patients with systemic rheumatic diseases: a meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to compare the diagnostic performance
      of procalcitonin and C-reactive protein (CRP) for bacterial infection in patients
      with systemic rheumatic diseases. METHODS: We searched Medline, Embase, and the
      Cochran library, and performed two meta-analyses on the diagnostic accuracy of
      procalcitonin and CRP for bacterial infection in systemic rheumatic disease
      patients. RESULTS: A total of eight studies including 668 patients in whom the
      patients with bacterial infection were 208 were available for the meta-analysis.
      The pooled sensitivity and specificity of procalcitonin were 66.8% (95%
      confidence interval [CI] 60.0-73.2) and 89.8% (86.6-92.4), respectively, and
      those of CRP were 81.3% (75.3-86.3) and 63.0% (58.5-67.5). Procalcitonin PLR,
      NLR, and DOR were 5.930 (3.593-9.786), 0.352 (0.229-0.539), and 19.33 (10.25
      36.45), respectively, and those for CRP were 2.228 (1.376-3.608), 0.367 (0.252
      0.534), and 7.066 (3.559-14.03), respectively. The AUC of procalcitonin was 0.884
      and the Q* index was 0.814, while the AUC of CRP was 0.789 and the Q* index was
      0.726, which indicated that the diagnostic accuracy of procalcitonin in patients
      with systemic rheumatic diseases is higher than that of CRP (difference of AUC
      0.095, 95% CI 0.004-0.185, p=0.039). When the data were limited to SLE, the
      specificity of procalcitonin was also significantly higher than that of CRP
      (difference 0.219, 95% CI 0.127-0.310, p<0.0001). CONCLUSIONS: Our meta-analysis
      of published studies demonstrates that procalcitonin is more specific and has
      better diagnostic accuracy than CRP for bacterial infection in systemic rheumatic
      diseases.

PMID- 25602441
TI  - Zearalenone and its metabolites in urine and breast cancer risk: a case-control
      study in Tunisia.
AB  - Zearalenone (ZON) is a non-steroidal estrogenic mycotoxin produced by Fusarium
      species. The exposure risk to humans and animals is the consumption of
      contaminated food and animal feeds. It has been reported that ZON and some of its
      metabolites promote the development of hormone-dependent tumors. The aim of this
      case-control study was to estimate exposure to ZON and its five metabolites
      (alpha-zearalenol [alpha-ZOL], beta-zearalenol [beta-ZOL], alpha-zearalanol
      [zeranol, alpha-ZAL], beta-zearalanol [teranol, beta-ZAL] and zearalanone [ZAN])
      by measuring urinary concentrations of these compounds, and to evaluate the risk
      of breast cancer related to this exposure. Chemical analyses were carried out by
      liquid-liquid extraction (LLE) and ultra-high performance liquid chromatography
      with tandem mass spectrometry detection (UHPLC-MS/MS). Statistical analyses were
      performed in order to determine the association between exposure to these
      compounds and the development of breast cancer. Crude and adjusted odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated by unconditional
      logistic regression to estimate the magnitude of the associations. The obtained
      results (adjusted OR=1.54, 95% CI=1.10-2.77) suggest a potential role of alpha
      ZAL in the risk of developing breast cancer. 

PMID- 25602443
TI  - Exploring Primary and Secondary Variants of Psychopathy in Adolescents in
      Detention and in the Community.
AB  - The current study aims to ascertain how different variants of callous-unemotional
      traits differ in their psychopathology, exposure to aggression and violence, and
      aggressive and violent behavior. If secondary/distressed variants (high in
      callous-unemotional traits and high in anxiety) and primary/traditional variants
      (high in callous-unemotional traits and low in anxiety) differ along these
      dimensions, it may speak to their different etiologies, treatment needs (e.g.,
      trauma focused), and responsiveness to treatment. The current sample consisted of
      799 adolescents from high schools (n = 419) and juvenile detention centers (n =
      380). Participants were interviewed regarding their callous-unemotional traits,
      psychopathology, exposure to aggression and violence, and aggressive and violent
      behavior. Parents/guardians and teachers/staff members also reported on
      participants' callous-unemotional traits and aggressive and violent behavior. A
      model-based cluster analysis indicated that there were four clusters in the data
      set, based on callous-unemotional traits and anxiety: a nonvariant cluster, a
      primary/traditional callous-unemotional cluster, a secondary/distressed callous
      unemotional cluster, and a "fearful" cluster. Secondary/distressed variants of
      psychopathy exhibited significantly greater symptoms of depression and
      psychoticism, more exposure to low level aggression and neighborhood violence,
      and more aggressive and violent behavior, as compared to the other clusters.
      Adolescents with callous-unemotional traits might not be a homogeneous group, but
      rather may differ in attitudes, behaviors, and exposure to risk, therefore
      differing in their treatment needs and responsiveness.

PMID- 25602445
TI  - Syntheses, structural, magnetic, and electron paramagnetic resonance studies of
      monobridged cyanide and azide dinuclear copper(II) complexes: antiferromagnetic
      superexchange interactions.
AB  - The reactions of Cu(ClO4)2 with NaCN and the ditopic ligands m-bis[bis(1
      pyrazolyl)methyl]benzene (Lm) or m-bis[bis(3,5-dimethyl-1
      pyrazolyl)methyl]benzene (Lm*) yield [Cu2(MU-CN)(MU-Lm)2](ClO4)3 (1) and [Cu2(MU
      CN)(MU-Lm*)2](ClO4)3 (3). In both, the cyanide ligand is linearly bridged (MU
      1,2) leading to a separation of the two copper(II) ions of ca. 5 A. The geometry
      around copper(II) in these complexes is distorted trigonal bipyramidal with the
      cyanide group in an equatorial position. The reaction of [Cu2(MU-F)(MU
      Lm)2](ClO4)3 and (CH3)3SiN3 yields [Cu2(MU-N3)(MU-Lm)2](ClO4)3 (2), where the
      azide adopts end-on (MU-1,1) coordination with a Cu-N-Cu angle of 138.0 degrees 
      and a distorted square pyramidal geometry about the copper(II) ions. Similar
      chemistry in the more sterically hindered Lm* system yielded only the
      coordination polymer [Cu2(MU-Lm*)(MU-N3)2(N3)2]. Attempts to prepare a dinuclear
      complex with a bridging iodide yield the copper(I) complex [Cu5(MU-I4)(MU
      Lm*)2]I3. The complexes 1 and 3 show strong antiferromagnetic coupling, -J = 135
      and 161 cm(-1), respectively. Electron paramagnetic resonance (EPR) studies
      coupled with density functional theory (DFT) calculations show that the exchange
      interaction is transmitted through the dz(2) and the bridging ligand s and px
      orbitals. High field EPR studies confirmed the dz(2) ground state of the
      copper(II) ions. Single-crystal high-field EPR has been able to definitively show
      that the signs of D and E are positive. The zero-field splitting is dominated by
      the anisotropic exchange interactions. Complex 2 has -J = 223 cm(-1) and DFT
      calculations indicate a predominantly d(x(2)-y(2)) ground state.

PMID- 25602444
TI  - The association between preoperative serum C-reactive protein and hepatocellular
      carcinoma recurrence in patients with chronic hepatitis B virus (HBV) infection-
      a retrospective study.
AB  - The prognosis of the patients with hepatocellular carcinoma (HCC) recurrence
      following curative hepatectomy is usually dismal. Whether preoperative serum C
      reactive protein (CRP) can predict the recurrence of HCC in patients with chronic
      HBV infection is not clear. Total 232 patients with chronic HBV infection were
      included in this retrospective study. We investigated the association between
      detailed preoperative serum CRP levels and early (<= 2 year) and late (> 2 year)
      HCC recurrence following curative hepatectomy. After adjusting for potential
      confounders, we found a saturation effect for preoperative serum CRP of 2.1 mg/dl
      existed for early HCC recurrence (ER). The incidence of ER increased with
      preoperative serum CRP less than 2.1 mg/dl (OR = 3.5, 95% CI 1.6-7.6, P = 0.001),
      and higher preoperative serum CRP (>2.1 mg/dl) did not increase the incidence of
      ER (OR = 0.8, 95% CI 0.2-2.7, P = 0.703). Whereas there is a linear relationship
      between preoperative serum CRP and late HCC recurrence (LR) (OR = 0.2, 95% CI,
      0.1- 0.4) (OR = 1.8, 95% CI, 1.2-2.5, P = 0.002). In addition, the optimal cutoff
      point for serum CRP level was 1.5 mg/dl, instead of 1.0 mg/dl, in predicting both
      ER and LR. Patients with higher preoperative serum CRP level (>1.5 mg/dl) had
      lower recurrence free survival rates and overall survival rates (P<0.01). These
      results suggest that preoperative serum CRP played different roles on ER and LR
      following curative hepatectomy, thus further predicting the prognosis in patients
      with chronic HBV infection.

PMID- 25602446
TI  - Images of otoscopy: rate and extent of non-compliance with good practice
      standards.
AB  - BACKGROUND: The British Society of Audiology has produced clear guidelines as to
      how otoscopy should be undertaken; however, no nationally recognised guidelines
      exist for the wider clinical community. Images of otoscopy appear in many books,
      journals, magazines and websites. OBJECTIVE: This study aimed to determine the
      rate of non-compliance with good practice in images of otoscopy, the seriousness
      of the breach, and whether this is more common in sites for professionals or the
      general public. METHOD: Google Images was searched using the terms 'otoscopy' and
      'ear examination'. A total of 200 images were identified and collated. The images
      were reviewed for compliance with good practice standards. RESULTS: Only 12.75
      per cent of the images were graded as having no breach of good practice
      standards. CONCLUSION: Professional websites have a responsibility to show best
      practice. When choosing an image, the source of the image needs to be carefully
      considered.

PMID- 25602447
TI  - Forward to the past.

PMID- 25602448
TI  - An update of the role of renin angiotensin in cardiovascular homeostasis.
AB  - The renin angiotensin system (RAS) is thought to be the body's main
      vasoconstrictor system, with physiological effects mediated via the interaction
      of angiotensin II with angiotensin I receptors (the "classic" RAS model).
      However, since the discovery of the heptapeptide angiotensin 1-7 and the
      development of the concept of the "alternate" RAS system, with its ability to
      reduce arterial blood pressure, our understanding of this physiologic system has
      changed dramatically. In this review, we focus on the newly discovered functions
      of the RAS, particularly the potential clinical significance of these
      developments, especially in the realm of new pharmacologic interventions for
      treating cardiovascular disease. 

PMID- 25602449
TI  - Cardiac rupture from blunt chest trauma diagnosed on transesophageal
      echocardiography.

PMID- 25602450
TI  - Fulminant myocarditis: the role of perioperative echocardiography.

PMID- 25602451
TI  - Coronary artery to left ventricle fistulas after septal myectomy.

PMID- 25602452
TI  - Gas analysis using Raman spectroscopy demonstrates the presence of
      intraperitoneal air (nitrogen and oxygen) in a cohort of children undergoing
      pediatric laparoscopic surgery.
AB  - Clinically significant gas embolism during laparoscopy is a rare but potentially
      catastrophic event. Case reports suggest that air, in addition to the
      insufflation gas, may be present. We studied the effects of equipment design and
      flushing techniques on the composition of gas present under experimental and
      routine pediatric surgical conditions. Concentrations of nitrogen (N2), oxygen
      (O2), and carbon dioxide (CO2) were measured by Raman spectroscopy in gas
      delivered to and retrieved from a mock peritoneum during simulated laparoscopy.
      We then analyzed the composition of insufflated and recovered gases during
      elective laparoscopic procedures conducted with CO2-preflushed and unflushed
      tubing to determine the presence of significant (10%) quantities of air. In
      vitro, CO2 was not detected at the distal end of insufflator tubing until after
      delivery of approximately 0.2 L of gas, and N2 persisted until >0.4 L was
      delivered, with 40% +/- 8% (mean +/- SD, range 33%-49%) recovered from the mock
      peritoneum at the termination of initial insufflation. In clinical studies,
      preflushing reduced the initial concentration of N2 from 78% +/- 0.5% to 23% +/-
      15%, but >10% air was detected in all subsequent samples, regardless of
      insufflation technique. Laparoscopic equipment and practice routinely permit
      delivery of air to the insufflated cavity. Purging the equipment with CO2 reduces
      but does not eliminate air (N2, O2) within the peritoneal cavity during
      laparoscopy. Thus, when vascular injury occurs, embolized gases will contain
      variable quantities of N2, O2, and CO2. As the initial insufflation volume
      diminishes and approaches the volume of the insufflation tubing, which occurs in
      infants and young pediatric patients, the concentration of N2 will approximate
      that of room air in an unflushed system. Small insufflation volumes containing
      high N2 concentrations can contribute to catastrophic air emboli in neonates and
      small pediatric patients. 

PMID- 25602453
TI  - The impact of targeted therapies for pulmonary hypertension on pediatric
      intraoperative morbidity or mortality.
AB  - BACKGROUND: Pulmonary hypertension (PHT) is a significant risk factor for major
      adverse events during anesthesia, with a reported incidence of 5% to 7%,
      secondary to acute pulmonary hypertensive crises or right ventricular ischemia.
      Newer therapies for treating PHT have reduced mortality. In this single-center
      study, we investigated the frequency of major and minor events during anesthesia
      under the current strategies to manage PHT. METHODS: We reviewed the records of
      children with PHT who underwent noncardiopulmonary bypass procedures from 2008 to
      2012. Clinically important symptoms, physical signs, and results of
      investigations present before anesthesia were recorded. The incidence and type of
      intraoperative complications and death (up to 7 days) were collected. RESULTS:
      Data were collected for 122 patients undergoing 284 procedures. Minor (3.9%) and
      major (3.2%) complication rates were unchanged from previous publications. The
      etiology of PHT was not significant for complications (P = 0.14). Disease
      modifying agents were not associated with reduced complications: 4.1% in treated
      versus 8.6% untreated (all P > 0.14). Patients receiving home oxygen had more
      complications (P = 0.02). Multiple logistic regression identified age and degree
      of PHT as significant predictors of complications (all P <= 0.03). CONCLUSIONS:
      The risk for adverse events during anesthesia in patients with PHT remains high,
      despite newer disease-modifying treatments. Risk factors for complications
      include age and severity of PHT.

PMID- 25602454
TI  - What can the national quality forum tell us about performance measurement in
      anesthesiology?
AB  - BACKGROUND: Anesthesiologists face increasing pressure to demonstrate the value
      of the care they provide, whether locally or nationally through public reporting
      and payor requirements. In this article, we describe the current state of
      performance measurement in anesthesia care at the national level and highlight
      gaps and opportunities in performance measurement for anesthesiologists. METHODS:
      We evaluated all endorsed performance measures in the National Quality Forum
      (NQF), the clearinghouse for all federal performance measures, and classified all
      measures as follows: (1) anesthesia-specific; (2) surgery-specific; (3) jointly
      attributable; or (4) other. We used NQF-provided descriptors to characterize
      measures in terms of (1) structure, process, outcome, or efficiency; (2)
      patients, disease, and events targeted; (3) procedural specialty; (4) reporting
      eligibility; (5) measures stewards; and (6) timing in the care stream. RESULTS:
      Of the 637 endorsed performance measures, few (6, 1.0%) were anesthesia-specific.
      An additional 39 measures (6.1%) were surgery-specific, and 67 others (10.5%)
      were jointly attributable. "Anesthesia-specific" measures addressed preoperative
      antibiotic timing (n = 4), normothermia (n = 1), and protocol use for the
      placement of central venous catheter (n = 1). Jointly attributable measures
      included outcome measures (n = 49/67, 73.1%), which were weighted toward
      mortality alone (n = 24) and cardiac surgery (n = 14). Other jointly attributable
      measures addressed orthopedic surgery (n = 4), general surgical oncologic
      resections (n = 12), or nonspecified surgeries (n = 15), but none specifically
      addressed anesthesia care outside the operating room such as for endoscopy. Only
      4 measures were eligible for value-based purchasing. No named anesthesiology
      professional groups were among measure stewards, but surgical professional groups
      (n = 33/67, 47%) were frequent measure stewards. CONCLUSIONS: Few NQF performance
      measures are specific to anesthesia practice, and none of these appears to
      demonstrate the value of anesthesia care or differentiate high-quality providers.
      To demonstrate their role in patient-centered, outcome-driven care,
      anesthesiologists may consider actively partnering in jointly attributable or
      team-based reporting. Future measures may incorporate surgical procedures not
      proportionally represented, as well as procedural and sedation care provided in
      nonoperating room settings.

PMID- 25602455
TI  - Deliberate practice for achieving and maintaining expertise in anesthesiology.
AB  - For the dedicated anesthesiologist, a high level of expertise is needed to
      deliver good care to patients and to provide excellent service to surgeons,
      anesthesia colleagues, and others. Expertise helps the anesthesiologist recover
      from difficult situations and generally makes the practice run more effectively.
      Expertise also contributes to quality of life through higher self-esteem and long
      term career satisfaction. We begin by reviewing the attributes that characterize
      expert performance and discussing how a specific training format, known as
      deliberate practice, contributes to acquisition and maintenance of expertise.
      Deliberate practice involves rehearsal of specific tasks to mastery, ideally
      under the eye of a mentor to provide feedback. This amounts to an orchestrated
      effort to improve that enables trainees to progress to expert levels of
      performance. With few exceptions, people who become recognized experts have
      pursued deliberate practice on the order of 4 hours per day for 10 to 15 years.
      In contrast, those who practice their profession in a rote manner see their
      skills plateau well below the level of top performers. Anesthesiology instruction
      with attending supervision provides all of the necessary components for
      deliberate practice, and it can be effective in anesthesia. Using deliberate
      practice in teaching requires organization in selecting training topics, effort
      in challenging students to excel, and skill in providing feedback. In this
      article, we discuss how educational programs can implement deliberate practice in
      anesthesiology training, review resources for instructors, and suggest how
      anesthesiologists can continue the practice after residency. 

PMID- 25602456
TI  - A pilot study on the effect of nasal continuous positive airway pressure on
      arterial partial pressure of carbon dioxide during spinal anesthesia with
      intravenous sedation for total knee arthroplasty.
AB  - BACKGROUND: Deep sedation of surgical patients may be associated with
      hypoventilation, airway collapse, and hypercarbia, although the extent of
      hypercarbia is rarely quantified. In this prospective, randomized, controlled
      clinical pilot study, we assessed the efficacy of nasal continuous positive
      airway pressure (nCPAP) for reducing arterial partial pressure of carbon dioxide
      (PaCO2) among deeply sedated, spontaneously ventilated patients undergoing total
      knee arthroplasty (TKA) under subarachnoid block (SAB), versus standard airway
      management in a control group. METHODS: Forty ASA status I-III patients underwent
      deep sedation with propofol to level 2 on the Modified Observers Assessment of
      Alertness/Sedation Scale during TKA performed under SAB. Nasal or oral airways
      were placed at the discretion of the anesthesia team, but they were not used in
      conjunction with nCPAP. Baseline arterial blood gas analysis (ABG-1) was
      performed after Modified Observers Assessment of Alertness/Sedation Scale level 2
      was reached. Patients were then randomized to receive nCPAP (nCPAP group, N = 20)
      or standard oxygen mask management (control group, N = 20). A second ABG (ABG-2)
      was performed 30 minutes later to assess the effect of nCPAP on PaCO2. The
      primary efficacy end point was change in PaCO2 from baseline to the 30-minute
      time point. RESULTS: Baseline (ABG-1) PaCO2 values were similar between nCPAP and
      control groups with median values of 54.5 and 56.1 mm Hg, respectively. There was
      a significant decline in PaCO2 in the nCPAP group (median of -4.6 mm Hg [10th
      90th quantile, -14.55 to 3.85]) as compared with the control group (median of
      0.95 mm Hg [-4.75 to 9.85]; P = 0.015; 95% confidence interval [CI] for location
      shift = -9.5 to -1.3). Within the control group, PaCO2 was similar from ABG-1 to
      ABG-2 (median [10th-90th quantile] = 56.1 mm Hg [47.2-67.0] vs 56.6 mm Hg [46
      68.8]; P = 0.52; 95% CI for the median = -3.4 to 3.4). Forty percent of all
      patients received an airway before ABG-1. The baseline PaCO2 value of patients
      receiving an airway was not different from that of patients without an airway
      (median [10th-90th quantile] = 56.0 mm Hg [46.0-68.4] vs 54.1 mm Hg [45.6-65.6],
      respectively; P = 0.33; 95% CI for location shift = -2.30 to 7.20). CONCLUSIONS:
      Deep sedation of TKA patients during SAB resulted in moderate hypercarbia (mean
      and median PaCO2 = 55). There was a trend showing that nCPAP treatment reduced
      PaCO2 versus treatment for control group patients receiving standard airway
      management; however, estimated treatment difference varied widely, from 1.4 to
      12.6 mm Hg. Among control group patients, the initial PaCO2 during deep sedation
      was similar to the PaCO2 when measured after a 30-minute period of continued deep
      sedation. Finally, baseline PaCO2 among deeply sedated patients who received an
      airway was not different from that of patients who did not receive an airway.

PMID- 25602457
TI  - Can anesthesiologists help? Analysis of the american heart association-emergency
      cardiac care recommendations for cardiopulmonary resuscitation, with a focus on
      management of airway and breathing.

PMID- 25602458
TI  - The elephant in the room is bigger than you think: finding obstructive sleep
      apnea patients dead in bed postoperatively.

PMID- 25602459
TI  - In response.

PMID- 25602460
TI  - Low vitamin D level: cause or marker for perioperative complications?

PMID- 25602461
TI  - In response.

PMID- 25602462
TI  - Engineering light outcoupling in 2D materials.
AB  - When light is incident on 2D transition metal dichalcogenides (TMDCs), it engages
      in multiple reflections within underlying substrates, producing interferences
      that lead to enhancement or attenuation of the incoming and outgoing strength of
      light. Here, we report a simple method to engineer the light outcoupling in
      semiconducting TMDCs by modulating their dielectric surroundings. We show that by
      modulating the thicknesses of underlying substrates and capping layers, the
      interference caused by substrate can significantly enhance the light absorption
      and emission of WSe2, resulting in a ~11 times increase in Raman signal and a ~30
      times increase in the photoluminescence (PL) intensity of WSe2. On the basis of
      the interference model, we also propose a strategy to control the photonic and
      optoelectronic properties of thin-layer WSe2. This work demonstrates the
      utilization of outcoupling engineering in 2D materials and offers a new route
      toward the realization of novel optoelectronic devices, such as 2D LEDs and solar
      cells. 

PMID- 25602463
TI  - Association between rice consumption and selected indicators of dietary and
      nutritional status using National Health and Nutrition Examination Survey 2007
      2008.
AB  - The present study was aimed at evaluating whether white rice, brown rice, and
      rice flour consumption has any association with selected measures of dietary
      intake and nutritional status, including various variables of energy intake,
      major vitamin and mineral intakes, weigh status, blood pressure, cholesterol
      level, and serum folate level for adults 20 years and older. Data from the
      National Health and Nutrition Examination Survey (NHANES) 2007-2008 and the Food
      Commodity Intake Database were used. Rice consumers had a significantly higher
      energy intake, yet they had lower percentage calorie intake from fat and
      saturated fat. Rice consumers also had significantly higher intakes of a range of
      nutrients. Rice consumers had lower waist circumference, triceps skinfold, and
      were significantly more likely to have a body mass index less than or equal to
      25. 

PMID- 25602464
TI  - Maximum common substructure-based data fusion in similarity searching.
AB  - Data fusion has been shown to work very well when applied to fingerprint-based
      similarity searching, yet little is known of its application to maximum common
      substructure (MCS)-based similarity searching. Two similarity search applications
      of the MCS will be focused on here. Typically, the number of bonds in the MCS, as
      well as the bonds in the two molecules being compared, are used in a similarity
      coefficient. The power of this technique can be extended using data fusion, where
      the MCS similarities of a set of reference molecules against one database
      molecule are fused. This "group fusion" technique forms the first application of
      the MCS in this work. The other application is that of the chemical
      hyperstructure. The hyperstructure concept is an alternative form of data fusion,
      being a hypothetical molecule that is constructed from the overlap of a set of
      existing molecules. This paper compares fingerprint group fusion (extended
      connectivity fingerprints), MCS similarity group fusion, and hyperstructure
      similarity searching, and describes their relative merits and complementarity in
      virtual screening. It is concluded that the hyperstructure approach as
      implemented here is less generally effective than conventional fingerprint
      approaches. 

PMID- 25602466
TI  - Anxiety and depression among African American women: The costs of strength and
      negative attitudes toward psychological help-seeking.
AB  - The Strong Black Woman (SBW) race-gender schema prompts African American women to
      use self-reliance and self-silence as coping strategies in response to stressors.
      Utilizing the coping strategies associated with the SBW race-gender schema could
      trigger anxiety and depression symptoms that may intensify when coupled with
      negative attitudes toward professional psychological help. The present study
      investigated whether African American women's endorsement of the SBW race-gender
      schema predicted increased symptoms of anxiety and depression and whether
      attitudes toward professional psychological help-seeking intensified
      psychological distress. Data were collected from 95 participants ranging in age
      from 18 to 65. Hierarchical regression analysis demonstrated significant main
      effects for the SBW race-gender schema and greater anxiety and depression,
      respectively. Greater indifference to stigma, 1 dimension of help-seeking
      attitudes, predicted lower levels of anxiety. African American women's attitudes
      toward professional help-seeking did not moderate the associations between
      endorsement of the SBW race-gender schema and anxiety or depression,
      respectively. Finally, endorsement of the SBW race-gender schema was inversely
      and significantly associated with 2 facets of help-seeking attitudes: (a)
      psychological openness and (b) help-seeking propensity. Taken together, these
      findings provide empirical support for the role of cultural factors, like the SBW
      race-gender schema, in African American women's experience of psychological
      distress and potential underutilization of mental health services. Future
      research directions are discussed. (PsycINFO Database Record 

PMID- 25602465
TI  - Cultural accommodation of group substance abuse treatment for Latino adolescents:
      Results of an RCT.
AB  - Comparative studies examining the difference between empirically supported
      substance abuse treatments versus their culturally accommodated counterparts with
      participants from a single ethnic minority group are frequently called for in the
      literature but infrequently conducted in practice. This randomized clinical trial
      was conducted to compare the efficacy of an empirically supported standard
      version of a group-based cognitive-behavioral treatment (S-CBT) to a culturally
      accommodated version (A-CBT) with a sample of Latino adolescents primarily
      recruited from the juvenile justice system. Development of the culturally
      accommodated treatment and testing was guided by the Cultural Accommodation Model
      for Substance Abuse Treatment (CAM-SAT). Seventy Latino adolescents (mean age =
      15.2; 90% male) were randomly assigned to 1 of 2 group-based treatment conditions
      (S-CBT = 36; A-CBT = 34) with assessments conducted at pretreatment,
      posttreatment, and 3-month follow-up. Longitudinal Poisson mixed models for count
      data were used to conduct the major analyses. The primary outcome variable in the
      analytic models was the number of days any substance was used (including alcohol,
      except tobacco) in the past 90 days. In addition, the variables ethnic identity,
      familism, and acculturation were included as cultural moderators in the analysis.
      Although both conditions produced significant decreases in substance use, the
      results did not support a time by treatment condition interaction; however,
      outcomes were moderated by ethnic identity and familism. The findings are
      discussed with implications for research and practice within the context of
      providing culturally relevant treatment for Latino adolescents with substance use
      disorders.

PMID- 25602467
TI  - Racial differences in sexual prejudice and its correlates among heterosexual men.
AB  - Previous research has consistently found sexual prejudice to be a predictor of
      antigay aggression and has also revealed specific correlates and antecedents of
      sexual prejudice. However, extant literature reveals mixed findings about
      potential racial group differences in sexual prejudice, and few studies have
      examined racial differences in the correlates of sexual prejudice. The aims of
      this descriptive study were to determine whether there are (a) racial group
      differences in reports of sexual prejudice and (b) racial group differences in
      previously identified correlates of sexual prejudice. Participants were 195
      heterosexual males, ages 18 to 30 (98 Blacks and 97 Whites), recruited from a
      large metropolitan city in the southeastern United States. Based on cultural
      differences in the influence of religion and in attitudes about male sexuality,
      it was hypothesized that Black participants would report higher sexual prejudice
      than White participants. Additionally, based on cultural differences in racial
      views on masculinity and in sociocultural experiences of male gender roles, it
      was hypothesized that Blacks would report greater endorsement of religious
      fundamentalism and the traditional male role norm of status than Whites. Results
      confirmed all of the hypothesized racial differences and revealed additional
      differences, including a differential effect of the traditional male role norm of
      status on sexual prejudice, which explains, at least in part, the racial
      differences found in sexual prejudice. These findings may reflect underlying
      cultural differences between Black and White males and may aid in the development
      of future efforts to reduce sexual prejudice and consequently antigay aggression
      toward sexual minorities.

PMID- 25602468
TI  - Ethnic discrimination and Latino depression: The mediating role of traumatic
      stress symptoms and alcohol use.
AB  - Previous research has established a link between ethnic discrimination and poor
      mental health, yet the process by which this relationship occurs remains unclear.
      It has been hypothesized that the potential mechanisms accounting for the
      negative consequences of ethnic discrimination may be through stress responses
      and health behaviors (Pascoe & Smart Richman, 2009). The present study sought to
      examine the role of traumatic stress symptoms and alcohol use in mediating the
      relationship between ethnic discrimination and depressive symptoms. Two aspects
      of ethnic discrimination were assessed, namely source of discrimination and
      reaction to discrimination. The sample for the current study included 244 adult
      Latinos averaging approximately 40 years of age (SD = 15.29; range 18-85).
      Participants, which were comprised of mainly women (66%, n = 156), completed a
      series of paper-and-pencil questionnaires. Multiple mediator analyses revealed
      that, among U.S.-born but not foreign-born Latinos, both source of discrimination
      and reaction to discrimination were related to increased traumatic stress
      symptoms, which, in turn, was associated with depressive symptomatology. The
      traumatic stress symptoms pathway showed a robust indirect effect while alcohol
      use was not a statistically significant mediator. These major findings suggest
      that, while ethnic discrimination has a direct effect on depression, increased
      traumatic stress can account for this relationship particularly for U.S.-born
      Latinos. The findings are discussed within a stress and coping framework.
      (PsycINFO Database Record 

PMID- 25602469
TI  - Attributions and emotions regarding health care mistreatment impact continuity of
      care among Latino and Anglo American women.
AB  - Ethnic minority and lower socioeconomic status (SES) populations report less
      positive health care encounters and lower continuity of health care compared with
      higher SES and non-Latino White (Anglo) Americans. This study examined
      similarities and differences concerning the influence of patients' causal
      attributions for health care mistreatment and related emotions on continuity of
      health care among 335 Latin American (Latinas) and Anglo American women in
      Southern California. A mixed methods research approach was implemented to
      identify and assess perceptions of health care mistreatment, causal attributions
      for mistreatment, negative emotions, and continuity of cancer screening care.
      Multigroup structural equation modeling revealed that causal attributions for
      health care mistreatment and related emotions explained continuity of care above
      and beyond what was explained by patients' exposure to health care mistreatment
      alone, for both ethnic groups. Still, the improvement in variance accounted for
      by including attributions and emotions was considerably more for Latinas (194%)
      than Anglo women (109%). Compared with attributions having to do with the health
      care environment (e.g., time constraints), attributions to the health care
      professional (e.g., uncompassionate) were related to higher levels of negative
      emotions for both Latinas and Anglo women and lower continuity of care,
      particularly for Anglo women. Results also suggest that for Latinas continuity of
      care was more a function of the attribution-emotion process, particularly the
      negative emotions associated with attributions concerning mistreatment, whereas
      for Anglo women it was more a function of mistreatment and the attribution
      itself. Interventions designed to improve professionals' communication and
      interpersonal skills may help enhance continuity of health care and reduce health
      disparities. (PsycINFO Database Record 

PMID- 25602470
TI  - Effects of temperature on the morphological, polymeric, and mechanical properties
      of Staphylococcus epidermidis bacterial biofilms.
AB  - Changes in temperature were found to affect the morphology, cell viability, and
      mechanical properties of Staphylococcus epidermidis bacterial biofilms. S.
      epidermidis biofilms are commonly associated with hospital-acquired medical
      device infections. We observed the effect of heat treatment on three physical
      properties of the biofilms: the bacterial cell morphology and viability, the
      polymeric properties of the extracellular polymeric substance (EPS), and the
      rheological properties of the bulk biofilm. After application of a 1 h heat
      treatment at 45  degrees C, cell reproduction had ceased, and at 60  degrees C,
      cell viability was significantly reduced. Size exclusion chromatography was used
      to fractionate the extracellular polymeric substance (EPS) based on size.
      Chemical analysis of each fraction showed that the relative concentrations of the
      polysaccharide, protein, and DNA components of the EPS were unchanged by the heat
      treatment at 45 and 60  degrees C. The results suggest that the EPS molecular
      constituents are not significantly degraded by the temperature treatment.
      However, some aggregation on the scale of 100 nm was found by dynamic light
      scattering at 60  degrees C. Finally, relative to control biofilms maintained at
      37  degrees C, we observed an order of magnitude reduction in the biofilm yield
      stress after 60  degrees C temperature treatment. No such difference was found
      for treatment at 45  degrees C. From these results, we conclude that the yield
      stress of bacterial biofilms is temperature-sensitive and that this sensitivity
      is correlated with cell viability. The observed significant decrease in yield
      stress with temperature suggests a means to weaken the mechanical integrity of S.
      epidermidis biofilms with applications in areas such as the treatment of biofilm
      infected medical devices. 

PMID- 25602471
TI  - Ethical responsibilities of caring for patients with incidental thyroid nodules.

PMID- 25602472
TI  - Evolutionary divergence among Oligosarcus spp. (Ostariophysi, Characidae) from
      the Sao Francisco and Doce River basins: Oligosarcus solitarius Menezes, 1987
      shows the highest rates of chromosomal evolution in the Neotropical Region.
AB  - The Doce River, in southeastern Brazil, is a coastal drainage, configured since
      the Late Cretaceous, when South America separated from Africa. Of the 77 native
      fish species of the Doce River Basin, 37 are potentially endangered-Oligosarcus
      solitarius, Menezes 1987, is the only endemic species of the quaternary lakes in
      the middle portion of this drainage and Oligosarcus argenteus, Gunther 1864, is
      distributed in the Doce River channel and headwaters. This study characterizes
      the morphological, cytogenetic, and mitochondrial DNA variation in the
      Oligosarcus spp. populations from the Doce and Sao Francisco River Basins. The
      principal component analysis indicates three morphological groups. Cytogenetic
      data corroborate existence of the O. solitarius and O. argenteus fish species in
      the Doce River Basin, with high levels of population cytogenetic polymorphism.
      Taking into consideration the Pleistocene-Holocene formation of the lacustrine
      system in the middle Doce River, with low molecular differentiation and high
      levels of chromosomal variation among the O. solitarius populations, we concluded
      that O. solitarius has the highest rate of chromosomal evolution observed in
      Neotropical freshwater fishes. The morphological and cytogenetic patterns of the
      Oligosarcus sp. population collected at the Das Velhas River headwaters suggest
      that it may represent an undescribed species. 

PMID- 25602473
TI  - Zirconium ions up-regulate the BMP/SMAD signaling pathway and promote the
      proliferation and differentiation of human osteoblasts.
AB  - Zirconium (Zr) is an element commonly used in dental and orthopedic implants
      either as zirconia (ZrO2) or in metal alloys. It can also be incorporated into
      calcium silicate-based ceramics. However, the effects of in vitro culture of
      human osteoblasts (HOBs) with soluble ionic forms of Zr have not been determined.
      In this study, primary culture of human osteoblasts was conducted in the presence
      of medium containing either ZrCl4 or Zirconium (IV) oxynitrate (ZrO(NO3)2) at
      concentrations of 0, 5, 50 and 500 uM, and osteoblast proliferation,
      differentiation and calcium deposition were assessed. Incubation of human
      osteoblast cultures with Zr ions increased the proliferation of human osteoblasts
      and also gene expression of genetic markers of osteoblast differentiation. In 21
      and 28 day cultures, Zr ions at concentrations of 50 and 500 uM increased the
      deposition of calcium phosphate. In addition, the gene expression of BMP2 and BMP
      receptors was increased in response to culture with Zr ions and this was
      associated with increased phosphorylation of SMAD1/5. Moreover, Noggin suppressed
      osteogenic gene expression in HOBs co-treated with Zr ions. In conclusion, Zr
      ions appear able to induce both the proliferation and the differentiation of
      primary human osteoblasts. This is associated with up-regulation of BMP2
      expression and activation of BMP signaling suggesting this action is, at least in
      part, mediated by BMP signaling. 

PMID- 25602474
TI  - Relationship between molecular association and re-entrant phenomena in polar
      calamitic liquid crystals.
AB  - The relationship between molecular association and re-entrant phase behavior in
      polar calamitic liquid crystals has been explored in two families of materials:
      the 4'-alkoxy-4-cyanobiphenyls (6OCB and 8OCB) and the 4'-alkoxy-4
      nitrobiphenyls. Although re-entrant nematic phase behavior has previously been
      observed in the phase diagram of 6OCB/8OCB, this is not observed in mixtures of
      the analogous nitro materials. As there is no stabilization of the smectic A
      phase in mixture studies, it was conjectured that the degree of association for
      the nitro systems is greater than that for the cyano analogues. This hypothesis
      was tested by using measured dielectric anisotropies and computed molecular
      properties to obtain a value of the Kirkwood factor, g, which describes the
      degree of association of dipoles in a liquid. These computed values of g confirm
      that the degree of association for nitro materials is greater than that for cyano
      and offer a useful method for quantifying molecular association in systems
      exhibiting a re-entrant polymorphism. 

PMID- 25602475
TI  - [The urinary bacterial flora in patients with cutaneous ureterostomy].
AB  - Twenty-four patients with cutaneous ureterostomy at least 6 months after surgery
      were included in this study. Single-J ureteral catheters were indwelt in 7
      patients. Pouch urine was cultured and analyzed from asymptomatic patients and
      from those with pyelonephritis. Forty-eight bacterial strains were isolated from
      asymptomatic patients. Thirty-five of these strains consisting of 18 species were
      isolated from the patients without ureteral catheters. Enterococcus (E.) faecalis
      (20.0%), Klebsiella pneumoniae (11.4%) and Proteus (P.) mirabilis (11. 4%) were
      isolated at high frequency. One methicilline-resistant coagulase-negative
      Staphylococcus (MRCNS) strain was isolated. Thirteen bacterial strains consisting
      of 8 species were isolated from the patients with ureteral catheters. E. faecalis
      (23.1%), Eschericia (E.) coli (23.1%) and Pseudomonas (P.) aeruginosa (15.4%)
      were isolated at high frequency. One E. coli strain harboring extended-spectrum
      beta lactamase (ESBL) and one MRCNS strain were isolated. Pyelonephritis occurred
      in 5 patients 14 times during follow-up for at least 6 months after surgery. The
      patients with ureteral catheters suffered from pyelonephritis (4/7, 57.1%) more
      frequently as compared to the patients without catheters (1/17, 5.9%) (p =
      0.014). P. aeruginosa (26.9%), E. faecium (15.4%), and P. mirabilis (11.5%) were
      isolated inhigh frequency. One E. coli strain harboring ESBL and one P. mirabilis
      strain harboring ESBL were isolated. In conclusion, insertion of ureteral
      catheters in a cutaneous ureterostomy is a strong risk factor for pyelonephritis
      and development of antibiotic-resistant bacteria. Therefore, urine culture is
      important in these patients who are under surveillance.

PMID- 25602476
TI  - [Unilateral adrenal tuberculosis: a case report].
AB  - Computed tomography (CT) performed for a 75-year-old man as a follow-up
      examination for deep vein thrombosis in October 2010 revealed a left adrenal mass
      (diameter, 8 mm). In December 2012, the adrenal mass increased to 28 mm in
      diameter, and he was referred to our department. Several blood examinations
      revealed that the adrenal mass was non-functioning, and only peripheral lesions
      were observed to be enhanced by using CT in the arterial phase. Malignancy was
      suspected due to the irregular shape and growth of the mass, and left
      adrenalectomy was performed in February 2013. The histopathological diagnosis was
      adrenal mycobacteriosis, and clinical diagnosis was adrenal tuberculosis. No
      other tuberculosis infection-related lesion was detected, and the patient was
      treated with multidrug antituberculous chemotherapy. 

PMID- 25602477
TI  - [Conservative management of symptomatic or asymptomatic urinoma after grade III
      blunt renal trauma: a report of three cases].
AB  - The management of urinoma after blunt renal trauma is still controversial,
      ranging from percutaneous drainage or ureteral stent placement for the
      symptomatic urinoma and waiting for spontaneous vanishment of the asymptomatic
      urinoma. We present two cases of symptomatic urinoma and a case of asymptomatic
      urinoma after renal laceration. All patients underwent selective renal arterial
      embolization for vascular complications, including active bleeding,
      pseudoaneurysm and arteriovenous fistula. Urinomas, which had been observed in
      all cases gradually reduced and vanished 1-24 months later. All cases were
      successfully managed without catheterization or percutaneous drainage for
      urinoma. 

PMID- 25602478
TI  - [Presurgical treatment of axitinib reduced operation risk by downsizing the vena
      cava tumor thrombus in advanced renal cell carcinomas: two case reports].
AB  - In cases of advanced renal cell carcinoma with inferior vena cava (IVC) thrombus,
      surgical resection of both tumor and thrombus contributes to the improvement of
      patient's prognosis, but the risk of perioperative complication is still high. We
      experienced two cases of advanced renal tumors with IVC tumor thrombus down-sized
      by presurgical treatment of axitinib. Axitinib treatment showed a marked tumor
      reduction effect without any severe adverse event. We could remove both tumor and
      thrombus without perioperative complications. In these two cases, downsizing of
      IVC thrombus enabled us to reduce the extent of the surgery.

PMID- 25602479
TI  - [Perirenal malignant perivascular epithelioid cell tumor originating from right
      retroperitoneum: a case report].
AB  - A 51-year-old woman was admitted to our hospital for detailed examinations and
      medical treatment against the right retroperitoneum tumor and liver lesions.
      Computed tomography showed a 20 cm diameter enhanced mass in the right perirenal
      space and multiple liver metastases. Pathological examination by needle biopsy
      revealed a perivascular epithelioid cell tumor (PEComa). With weekly
      administration of a mTOR inhibitor, Temsirolimus, the tumor was reduced by about
      20% one month later. The maximal response was stable disease due to RECIST v 1.
      1. However, shortly after the minimal response, the disease showed progression.
      She died about five months after the start of molecular targeted therapy. In
      regard to the origin of PEComa, our report is the fifth in Japan as a case of
      retroperitoneal origin to the best of our knowledge. 

PMID- 25602480
TI  - [An ileal neobladder-enteric fistula 10 years after a radical cystectomy with
      ileal neobladder construction].
AB  - A 67-year-old male underwent a radical cystectomy and ileal neobladder
      construction in September 2002. He developed adhesive ileus postoperatively and
      underwent an intestine-ascending colon bypass operation with a side-to-side
      anastomosis in December of 2002. Subsequently, the patient developed ileus
      frequently, which improved with conservative management. In February 2013, he had
      fecaluria and was diagnosed with an ileal neobladder-enteric fistula based on
      computed tomography 2 hours after contrast medium injection. He underwent closure
      of the intestinal anal side of the anastomosis between the intestine and
      ascending colon. The fecaluria disappeared and he is making steady progress. An
      ileal neobladderenteric fistula as a long-term postoperative complication of
      ileal neobladder construction is extremely rare, with no other reports to our
      knowledge. Here, we discuss its cause, diagnosis and treatment, with reference to
      previous reports. 

PMID- 25602481
TI  - [A case of eosinophilic cystitis mimicking an invasive bladder cancer].
AB  - A 60-year-old woman was referred to our hospital because of gross hematuria,
      right lumbar pain and lower abdominal pain. Computed tomography (CT) scan
      revealed hydronephrosis of the right kidney, irregular bladder wall thickening at
      the right lateral and posterior portion and external iliac lymph node swelling of
      the right side. Laboratory data revealed disseminated intravascular coagulation
      syndrome (DIC) and eosinophilia. Because she developed a high fever that was
      caused by acute obstructive pyelonephritis of the right kidney, percutaneous
      nephrostomy was placed and the therapy for DIC was initiated. Pathological
      examination of transurethral resection of bladder tumor performed twice showed no
      malignancy but inflammatory infiltration of many eosinocytes, leading to the
      diagnosis of eosinophilic cystitis (EC). We considered the possibility of
      allergic reaction to the drugs she was taking as the etiology of EC and
      discontinued all drugs. Although eosinophilia was resolved afterward, she then
      developed brain infarction, followed by cerebral hemorrhage. She was transferred
      to a rehabilitation hospital for long-term care. CT scan that was performed 4
      months after the initial presentation showed the resolution of hydronephrosis of
      the right kidney and external iliac lymph node swelling and the improvement of
      bladder wall thickness. Hydronephrosis of the right kidney has not recurred after
      removing the nephrostomy catheter. EC is a rare condition that could mimic an
      invasive bladder cancer. EC should be considered if bladder tumor is associated
      with eosinophilia. Therapeutic consideration for thromboembolic events should be
      made in patients with EC. 

PMID- 25602482
TI  - [Docetaxel for small cell carcinoma of the prostate with a metastatic pelvic
      tumor: a case report].
AB  - Small cell carcinoma of the prostate is known to have a poor prognosis. We report
      a case of a large pelvic tumor with small cell carcinoma, which responded well to
      docetaxel. A 72-year-old man who was receiving androgen-deprivation therapy for
      prostatic adenocarcinoma presented with constipation. Although the prostate
      specific antigen level had decreased, a large pelvic tumor was detected between
      the prostate and the rectum, which caused bowel obstruction. A biopsy of the
      pelvic tumor revealed small cell carcinoma of the prostate, and chemotherapy with
      docetaxel and prednisolone was administered. Five months after the administration
      of docetaxel, the pelvic tumor disappeared completely. At the time of the last
      follow up, the response was still maintained. 

PMID- 25602483
TI  - [Small cell carcinoma of the prostate: a case report--a prognostic analysis of
      case reports and literature in Japan].
AB  - A 62-year-old Japanese man had been suffering from dysuria since January 2011.
      Since symptoms persisted regardless of antibiotics therapy at a urological
      clinic, he consulted our clinic in February 2011. Digital rectal examination
      revealed a large irregular and stony hard prostatic mass, with the serum
      prostated specific antigen (PSA) of 2.76 ng/ml. T2-weighted magnetic reasonance
      imaging showed diffuse hypointensity and sharp margin in prostatic peripheral
      zone. Transperineal biopsy of the prostate was performed in March 2011.
      Considering histopathological findings of tumor cells in all specimens combined
      with positive immunoreactivity of neoplastic cells to chromogranin A but negative
      immunoreactivity to PSA, we diagnosed him with small cell carcinoma. The whole
      body computed tomography showed no metastatic lesion, he was diagnosed with small
      cell carcinoma of the prostate at clinical stage T2cN0M0. He received 4 cycles of
      chemotherapy (cisplatinum and etoposide) and underwent external beam radiotherapy
      to the pelvis and prostate, up to a total dose of 64 Gy. The urologic and
      radiologic outcomes including the serum levels of neuron-specific enolase and pro
      gastrin releasing peptide have been satisfactory after more than 3 years of
      follow-up.

PMID- 25602484
TI  - [Burned-out testicular tumor diagnosed triggered by paraneoplastic neurological
      syndrome: a case report].
AB  - We report a case of burned-out testicular tumor. A 41-year-old man was referred
      to our department with swelling of iliac lymph nodes detected by computed
      tomography screening for cerebellar atrophy. Lymph node biopsy revealed
      metastasis of seminoma. Ultrasound examination showed an irregular hypoechoic
      area in his left testis. We diagnosed paraneoplastic neurological syndrome
      secondary to burned-out testicular tumor. So, we underwent left orchiectomy and
      chemotherapy. He remains free from disease recurrence 15 months after treatment.

PMID- 25602485
TI  - Role of the NO/cGMP pathway in postoperative vasodilation in perforator flaps.
AB  - BACKGROUND: The nitric oxide (NO)/cyclic guanylyl monophosphate (cGMP) pathway is
      one of the most important regulators of tissue perfusion. Here, we sought to
      elucidate the protective effects of the NO/cGMP pathway on the microcirculation
      of axial pattern skin flaps. MATERIAL AND METHODS: Overall 40 rats were divided
      into four groups (n = 10 each): group A, sildenafil was administered orally at 10
      mg/kg daily; group B, sildenafil citrate (10 mg/kg, oral) and nitro-amino-methyl
      L-arginine (L-NAME, intraperitoneal injection), a nitric oxide synthase
      inhibitor, were administered daily; group C, L-NAME was administered alone; and
      group D, no drugs were administered. After surgery, the surviving flap area was
      calculated as a percentage of total flap dimensions using the paper template
      technique. Angiography and imaging were performed to compare the macrovascular
      changes of the choke zones in the flaps. Histological examinations were performed
      to compare the differences in microvascular changes between the two choke zones.
      RESULTS: A significant improvement of flap survival area and a significant
      dilation of vessels in both choke zones were found after administration of
      sildenafil. We also found that the postoperative vasodilation of choke vessels
      could be altered by inhibition of NO synthase (NOS). Moreover, the vasodilatory
      effect prolonged by the phosphodiesterase 5 inhibitor sildenafil was attenuated
      after administration of L-NAME. L-NAME significantly reversed the protection
      afforded by sildenafil. CONCLUSIONS: Targeting the NO/cGMP pathway can dilate
      vessels along the axis of the flap, including the choke vessels, thus augmenting
      flap viability. Therefore, targeting of this pathway may have therapeutic
      applications.

PMID- 25602486
TI  - In Vitro Effects of Mucus from the Mantle of Compatible (Lymnaea elodes) and
      Incompatible (Helisoma trivolvis) Snail Hosts on Fascioloides magna Miracidia.
AB  - The epidermal mucus covering the surface of a snail represents an important
      barrier to trematode larvae attempting to penetrate the snail and may play a role
      in mediating snail-trematode compatibility. In this study, Facioloides magna
      miracidia were exposed to mucus harvested from a compatible snail host, Lymnaea
      elodes (palustris), and from an incompatible snail, Helisoma trivolvis . In vitro
      treatment of freshly hatched miracidia with snail-derived mucus exerted
      dramatically different effects on larvae depending on snail species. At the
      lowest dilution of mucus tested (1:3) mean damage rates (tegumental damage and/or
      larval lysis and death) were as high as 100% for miracidia exposed to H.
      trivolvis mucus, while none of F. magna miracidia were damaged in L. elodes
      mucus. A dilution series for each snail species, and treatments with heat and
      proteinase K were performed to characterize the component(s) of mucus inducing
      the observed morphological changes. The damaging effects of H. trivolvis mucus
      were concentration dependent and completely abrogated by heat (65 C, 30 min) and
      proteinase treatment, strongly implicating a heat-labile protein(s) in mucus as
      the active cytotoxic agent(s). In contrast to our prediction that miracidial
      contact with mucus of compatible L. elodes would trigger larval transformation,
      mucus from either snail species tested exhibited little to no activity. Overall
      these data demonstrate the presence of a potent cytotoxic protein-like factor in
      the mucus of F. magna -incompatible H. trivolvis , and its absence in the mucus
      of the compatible snail, L. elodes . This finding supports the notion that the
      epidermal mucus layer may be serving as an important determinant of larval
      trematode-snail compatibility. 

PMID- 25602487
TI  - Nanotoxicity of silver nanoparticles to red blood cells: size dependent
      adsorption, uptake, and hemolytic activity.
AB  - Silver nanoparticles (AgNPs) are increasingly being used as antimicrobial agents
      and drug carriers in biomedical fields. However, toxicological information on
      their effects on red blood cells (RBCs) and the mechanisms involved remain
      sparse. In this article, we examined the size dependent nanotoxicity of AgNPs
      using three different characteristic sizes of 15 nm (AgNPs15), 50 nm (AgNPs50),
      and 100 nm (AgNPs100) against fish RBCs. Optical microscopy and transmission
      electron microscopy observations showed that AgNPs exhibited a size effect on
      their adsorption and uptake by RBCs. The middle sized AgNPs50, compared with the
      smaller or bigger ones, showed the highest level of adsorption and uptake by the
      RBCs, suggesting an optimal size of ~50 nm for passive uptake by RBCs. The toxic
      effects determined based on the hemolysis, membrane injury, lipid peroxidation,
      and antioxidant enzyme production were fairly size and dose dependent. In
      particular, the smallest sized AgNPs15 displayed a greater ability to induce
      hemolysis and membrane damage than AgNPs50 and AgNPs100. Such cytotoxicity
      induced by AgNPs should be attributed to the direct interaction of the
      nanoparticle with the RBCs, resulting in the production of oxidative stress,
      membrane injury, and subsequently hemolysis. Overall, the results suggest that
      particle size is a critical factor influencing the interaction between AgNPs and
      the RBCs. 

PMID- 25602488
TI  - Engineering vascularized adipose tissue using the stromal-vascular fraction and
      fibrin hydrogels.
AB  - The development of vascularized and functional adipose tissue substitutes is
      required to improve soft tissue augmentation. In this study, vascularized adipose
      tissue constructs were generated using uncultured cells from the stromal-vascular
      fraction (SVF) of adipose tissue as an alternative cell source to adipose-derived
      stem cells. SVF cell behavior and tissue formation were compared in a stable
      fibrin formulation developed by our group and a commercial fibrin sealant
      (TissuCol; Baxter) upon direct subcutaneous implantation in a nude mouse model.
      Further, the effect of in vitro adipogenic induction on SVF cell development was
      investigated by implanting stable fibrin constructs after 1 week of
      precultivation (adipogenic vs. noninduced control). Constructs were thoroughly
      analyzed before implantation regarding adipogenic differentiation status, cell
      viability, and distribution as well as the presence of endothelial cells. Before
      implantation, in vitro precultivation strongly promoted adipogenesis (under
      adipogenic conditions) and the formation of CD31(+) prevascular structures by SVF
      cells (under nonadipogenic conditions). Tissue development in vivo was determined
      after 4 weeks by histology (hematoxylin and eosin, human vimentin) and quantified
      histomorphometrically. In stable fibrin gels, adipogenic precultivation was
      superior to noninduced conditions, resulting in mature adipocytes and the
      formation of distinct vascular structures of human origin in vivo. Strong
      neovascularization by the implanted cells predominated in noninduced constructs.
      Without pretreatment, the SVF in stable fibrin gels displayed only a weak
      differentiation capability. In contrast, TissuCol gels strongly supported the
      formation of coherent and well-vascularized adipose tissue of human origin,
      displaying large unilocular adipocytes. The developed native-like tissue
      architecture was highlighted by a whole mount staining technique. Taken together,
      SVF cells from human adipose tissue were shown to successfully lead to adipose
      tissue formation in fibrin hydrogels in vivo. The results render the SVF a
      promising cell source for subsequent studies both in vitro and in vivo with the
      aim of engineering clinically applicable soft tissue substitutes. 

PMID- 25602489
TI  - Interactive effects of working memory and trial history on Stroop interference in
      cognitively healthy aging.
AB  - Past studies have suggested that Stroop interference increases with age; however
      the robustness of this effect after controlling for processing speed has been
      questioned. Both working memory (WM) and the congruency of the immediately
      preceding trial have also been shown to moderate the magnitude of Stroop
      interference. Specifically, interference is smaller both for individuals with
      higher working memory capacity and following an incongruent trial. At present, it
      is unclear whether and how these 3 variables (age, WM and previous congruency)
      interact to predict interference effects in the standard Stroop color-naming
      task. We present analyses of Stroop interference in a large database of Stroop
      color-naming trials from a lifespan sample of well-screened, cognitively healthy,
      older adults. Our results indicated age-related increases in interference (after
      controlling for processing speed) that were exaggerated for individuals with low
      WM. This relationship between age and WM occurred primarily when the immediately
      preceding trial was congruent. Following an incongruent trial, interference
      increased consistently with age, regardless of WM. Taken together, these results
      support previous accounts of multiple mechanisms underlying control in the Stroop
      task and provide insight into how each component is jointly affected by age, WM,
      and trial history.

PMID- 25602490
TI  - Doubly blessed: older adults know more vocabulary and know better what they know.
AB  - This study examined age-related differences in the ability to judge one's
      vocabulary. Young, middle-age, and older adults completed a multiple-choice test
      of vocabulary, judged their confidence in each answer, and estimated their
      overall performance. Older adults performed better and were more confident in
      their knowledge than were the other 2 groups. Importantly, relative to young
      adults, older adults demonstrated better calibration both on item-by-item
      confidence judgments and on global estimates. Resolution, as defined by
      correlations between item-by-item performance and confidence judgments, was age
      invariant. We suggest that age-related accumulation of vocabulary is accompanied
      by enhanced perception of mastery in one's knowledge.

PMID- 25602491
TI  - Older adults can suppress unwanted memories when given an appropriate strategy.
AB  - Memory suppression refers to the ability to exclude distracting memories from
      conscious awareness, and this ability can be assessed with the think/no-think
      paradigm. Recent research with older adults has provided evidence suggesting both
      intact and deficient memory suppression. The present studies seek to understand
      the conditions contributing to older adults' ability to suppress memories
      voluntarily. We report 2 experiments indicating that the specificity of the
      think/no-think task instructions contributes to older adults' suppression
      success: When older adults receive open-ended instructions that require them to
      develop a retrieval suppression strategy on their own, they show diminished
      memory suppression compared with younger adults. Conversely, when older adults
      receive focused instructions directing them to a strategy thought to better
      isolate inhibitory control, they show suppression-induced forgetting similar to
      that exhibited by younger adults. Younger adults demonstrate memory suppression
      regardless of the specificity of the instructions given, suggesting that the
      ability to select a successful suppression strategy spontaneously may be
      compromised in older adults. If so, this deficit may be associated with
      diminished control over unwanted memories in naturalistic settings if impeded
      strategy development reduces the successful deployment of inhibitory control.

PMID- 25602492
TI  - Older adults' affective experiences across 100 days are less variable and less
      complex than younger adults'.
AB  - Older adults are often described as being more emotionally competent than younger
      adults, and higher levels of affect complexity are seen as an indicator of this
      competence. We argue, however, that once age differences in affect variability
      are taken into account, older adults' everyday affective experiences will be
      characterized by lower affect complexity when compared with younger adults'. In
      addition, reduced affect complexity seems more likely from a theoretical point of
      view. We tested this hypothesis with a study in which younger and older adults
      reported their momentary affect on 100 days. Affect complexity was examined using
      clusterwise simultaneous component analysis based on covariance matrices to take
      into account differences in affect variability. We found that in the majority of
      older adults (55%), structures of affect were comparatively simpler than those of
      younger adults because they were reduced to a positive affect component. Most
      remaining older adults (35%) were characterized by differentiated rather than
      undifferentiated affective responding, as were a considerable number of younger
      adults (43%). When affect variability was made comparable across age groups,
      affect complexity also became comparable across age groups. It is interesting
      that individuals with the least complex structures had the highest levels of well
      being. We conclude that affective experiences are not only less variable in the
      majority of older adults, but also less complex. Implications for understanding
      emotions across the life span are discussed.

PMID- 25602493
TI  - The longer-term effects of a brief hazard perception training intervention in
      older drivers.
AB  - Previous research has shown that drivers aged over 65 years can improve their
      scores in video-based hazard perception tests following training interventions.
      In order to examine the longer-term effects of hazard perception training, we
      recruited 75 drivers aged 65 and over. They either received a 35-min hazard
      perception training intervention or a placebo intervention. Significant decreases
      in hazard perception response time as a result of the training were found
      immediately after the intervention, and approximately 1 month and 3 months later.
      There was no significant decay in the training effect over this time period.

PMID- 25602494
TI  - Birth cohort differences in fluid cognition in old age: comparisons of trends in
      levels and change trajectories over 30 years in three population-based samples.
AB  - Later-born cohorts of older adults tend to outperform earlier born on fluid
      cognition (i.e., Flynn effect) when measured at the same chronological ages. We
      investigated cohort differences in level of performance and rate of change across
      three population-based samples born in 1901, 1906, and 1930, drawn from the
      Gerontological and Geriatric Population Studies in Gothenburg, Sweden (H70), and
      measured on tests of logical reasoning and spatial ability at ages 70, 75, and 79
      years. Estimates from multiple-group latent growth curve models (LGCM) revealed,
      in line with previous studies, substantial differences in level of performance
      where later-born cohorts outperformed earlier born cohorts. Somewhat
      surprisingly, later-born cohorts showed, on average, a steeper decline than the
      earlier-born cohort. Gender and education only partially accounted for observed
      cohort trends. Men outperformed women in the 1906 and 1930 cohorts but no
      difference was found in the 1901 cohort. More years of education was associated
      with improved performance in all three cohorts. Our findings confirm the presence
      of birth cohort effects also in old age but indicate a faster rate of decline in
      later-born samples. Potential explanations for these findings are discussed.

PMID- 25602495
TI  - Trap states in lead iodide perovskites.
AB  - Recent discoveries of highly efficient solar cells based on lead iodide
      perovskites have led to a surge in research activity on understanding photo
      carrier generation in these materials, but little is known about trap states that
      may be detrimental to solar cell performance. Here we provide direct evidence for
      hole traps on the surfaces of three-dimensional (3D) CH3NH3PbI3 perovskite thin
      films and excitonic traps below the optical gaps in these materials. The
      excitonic traps possess weak optical transition strengths, can be populated from
      the relaxation of above gap excitations, and become more significant as
      dimensionality decreases from 3D CH3NH3PbI3 to two-dimensional (2D)
      (C4H9NH3I)2(CH3NH3I)(n-1)(PbI2)(n) (n = 1, 2, 3) perovskites and, within the 2D
      family, as n decreases from 3 to 1. We also show that the density of excitonic
      traps in CH3NH3PbI3 perovskite thin films grown in the presence of chloride is at
      least one-order of magnitude lower than that grown in the absence of chloride,
      thus explaining a widely known mystery on the much better solar cell performance
      of the former. The trap states are likely caused by electron-phonon coupling and
      are enhanced at surfaces/interfaces where the perovskite crystal structure is
      most susceptible to deformation.

PMID- 25602497
TI  - Assessment of Nutrient Value and Microbiological Safety of Pomacea lineata.
AB  - Pomacea lineata is a fresh water shellfish that is utilized as food, medicinal
      portions, or licking remedies. The objective of this study was to evaluate the
      nutritional and microbiological aspects of P. lineata and spawning. The samples
      were collected in the Jaguaribe River (Paraiba, Brazil) during the rainy and dry
      seasons. The biochemical composition, mineral composition, total mesophilic
      bacteria (TMB), total coliforms (TC), fecal coliforms (FC), Salmonella sp.,
      Staphylococcus aureus, and Vibrio presence were determined. Each 100 g of P.
      lineata presented 3.1 g of ashes; 9.4 g of proteins; 2.7 g of lipids; 0.6 g of
      carbohydrates; 1800.0 mg of calcium; 78.0 mg of phosphorus, and 58.4 mg of iron.
      Each 100 g of spawning presented 10.4 g of ashes; 4.5 g of proteins; 2.8 g of
      lipids; 1.3 g of carbohydrates; 3633.0 mg of calcium; 39.4 mg of phosphorus; and
      4.6 mg of iron. Each 100 g of P. lineata provided 65.7 kcal and spawning 48.3
      kcal. In the dry season P. lineata and spawning showed no TMB and TC, FC, S.
      aureus, Salmonella, or Vibrio. In the rainy season P. lineata and spawning
      presented increase in TMB and TC, FC, S. aureus, and Salmonella. The presence of
      Vibrio was not detected. P. lineata presented proteins, low lipid, and
      carbohydrate content, energy values close to those of lean meats, high contents
      of calcium and iron, and presented low contamination level with pathogenic
      bacteria. Since P. lineata substances may be useful in the treatment of
      respiratory and gastrointestinal diseases without presenting toxic or cytotoxic
      effects already described in the literature, it may be considered as a potential
      functional food.

PMID- 25602496
TI  - Chlorhexidine bathing and health care-associated infections: a randomized
      clinical trial.
AB  - IMPORTANCE: Daily bathing of critically ill patients with the broad-spectrum,
      topical antimicrobial agent chlorhexidine is widely performed and may reduce
      health care-associated infections. OBJECTIVE: To determine if daily bathing of
      critically ill patients with chlorhexidine decreases the incidence of health care
      associated infections. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic cluster
      randomized, crossover study of 9340 patients admitted to 5 adult intensive care
      units of a tertiary medical center in Nashville, Tennessee, from July 2012
      through July 2013. INTERVENTIONS: Units performed once-daily bathing of all
      patients with disposable cloths impregnated with 2% chlorhexidine or
      nonantimicrobial cloths as a control. Bathing treatments were performed for a 10
      week period followed by a 2-week washout period during which patients were bathed
      with nonantimicrobial disposable cloths, before crossover to the alternate
      bathing treatment for 10 weeks. Each unit crossed over between bathing
      assignments 3 times during the study. MAIN OUTCOMES AND MEASURES: The primary
      prespecified outcome was a composite of central line-associated bloodstream
      infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs),
      ventilator-associated pneumonia (VAP), and Clostridium difficile infections.
      Secondary outcomes included rates of clinical cultures that tested positive for
      multidrug-resistant organisms, blood culture contamination, health care
      associated bloodstream infections, and rates of the primary outcome by ICU.
      RESULTS: During the chlorhexidine bathing period, 55 infections occurred: 4
      CLABSI, 21 CAUTI, 17 VAP, and 13 C difficile. During the control bathing period,
      60 infections occurred: 4 CLABSI, 32 CAUTI, 8 VAP, and 16 C difficile. The
      primary outcome rate was 2.86 per 1000 patient-days during the chlorhexidine and
      2.90 per 1000 patient-days during the control bathing periods (rate difference, 
      0.04; 95% CI, -1.10 to 1.01; P = .95). After adjusting for baseline variables, no
      difference between groups in the rate of the primary outcome was detected.
      Chlorhexidine bathing did not change rates of infection-related secondary
      outcomes including hospital-acquired bloodstream infections, blood culture
      contamination, or clinical cultures yielding multidrug-resistant organisms. In a
      prespecified subgroup analysis, no difference in the primary outcome was detected
      in any individual intensive care unit. CONCLUSION AND RELEVANCE: In this
      pragmatic trial, daily bathing with chlorhexidine did not reduce the incidence of
      health care-associated infections including CLABSIs, CAUTIs, VAP, or C difficile.
      These findings do not support daily bathing of critically ill patients with
      chlorhexidine. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02033187.

PMID- 25602498
TI  - Automatic framework for extraction and characterization of wetting front
      propagation using tomographic image sequences of water infiltrated soils.
AB  - This paper presents a new automatic framework for extracting and characterizing
      the dynamic shape of the 3D wetting front and its propagation, based in a
      sequence of tomographic images acquired as water (moisture) infiltrates in
      unsaturated soils. To the best of the authors' knowledge, the shape of the 3D
      wetting front and its propagation and progress over time has not been previously
      produced as a whole by methods in existing literature. The proposed automatic
      framework is composed two important and integrated modules: i) extraction of the
      3D wetting front, and ii) characterization and description of the 3D wetting
      front to obtain important information about infiltration process. The 3D wetting
      front surface is segmented from 3D CT imagery provided as input via a 3D
      stochastic region merging strategy using quadric-regressed bilateral space-scale
      representations. Based on the 3D segmentation results, the normal directions at
      local curvature maxima of the wetting front surface are computed for 3D images of
      soil moisture, and its propagation is analyzed at the local directions in sites
      of maximal water adsorption, and described using histograms of curvature changes
      over time in response to sample saturation. These curvature change descriptors
      provide indirect measurements of moisture infiltration in soils, and soil
      saturation. Results using a field tomograph equipment specific for soil studies
      are encouraging, and suggest that the proposed automatic framework can be applied
      to estimate the infiltration of water in soils in 3D and in time. 

PMID- 25602499
TI  - Comparison of confocal microscopy and two-photon microscopy in mouse cornea in
      vivo.
AB  - High-resolution imaging of the cornea is important for studying corneal diseases
      at cellular levels. Confocal microscopy (CM) has been widely used in the clinic,
      and two-photon microscopy (TPM) has recently been introduced in various pre
      clinical studies. We compared the performance of CM and TPM in normal mouse
      corneas and neovascularized mouse corneas induced by suturing. Balb/C mice and
      C57BL/6 mice expressing green fluorescent protein (GFP) were used to compare
      modalities based on intrinsic contrast and extrinsic fluorescence contrast. CM
      based on reflection (CMR), CM based on fluorescence (CMF), and TPM based on
      intrinsic/extrinsic fluorescence and second harmonic generation (SHG) were
      compared by imaging the same sections of mouse corneas sequentially in vivo. In
      normal mouse corneas, CMR visualized corneal cell morphologies with some
      background noise, and CMF visualized GFP expressing corneal cells clearly. TPM
      visualized corneal cells and collagen in the stroma based on fluorescence and
      SHG, respectively. However, in neovascularized mouse corneas, CMR could not
      resolve cells deep inside the cornea due to high background noise from the
      effects of increased structural irregularity induced by suturing. CMF and TPM
      visualized cells and induced vasculature better than CMR because both collect
      signals from fluorescent cells only. Both CMF and TPM had signal decays with
      depth due to the structural irregularity, with CMF having faster signal decay
      than TPM. CMR, CMF, and TPM showed different degrees of image degradation in
      neovascularized mouse corneas. 

PMID- 25602500
TI  - Genetic Characterization of ST195 and ST365 Carbapenem-Resistant Acinetobacter
      baumannii Harboring blaOXA-23 in Guangzhou, China.
AB  - We investigated the distribution of resistance genes and the clonal relationships
      among carbapenem-resistant Acinetobacter baumannii isolates from the intensive
      care unit wards of two hospitals in Guangzhou, China. From 2012 to 2013, 57 A.
      baumannii isolates were obtained from blood cultures from two hospitals in
      Guangzhou. The antibiotic resistance profiles were determined by using the Vitek2
      system and Etest strips. PCR was used to detect the genes encoding OXA-type
      carbapenemases and metallo-beta-lactamases and the presence of ISAba1 upstream of
      the bla(OXA-51-like) gene and the bla(OXA-23-like) gene. Multilocus sequence
      typing (MLST) and sequence-based typing of bla(OXA-51-like) genes (SBT-bla(OXA-51
      like )genes) were performed to analyze the genetic relationship of the isolates.
      Among the 57 isolates, 46 were carbapenem-resistant A. baumannii (CRAB) isolates.
      The bla(OXA-51-like) gene was identified in all 57 isolates, while the bla(OXA-23
      like) gene was present in all 46 CRAB isolates. The MLST analysis grouped the A.
      baumannii isolates into five existing sequence types (STs) and five new STs.
      Fifty-two isolates belonged to the worldwide spread of clonal complex 92 (CC92),
      among which ST195 and ST365 were the most common STs. The MLST data and SBT
      bla(OXA-51-like) genes showed that all isolates harboring the major bla(OXA-51
      like) alleles, such as bla(OXA-66), belonged to CC92.

PMID- 25602501
TI  - Relationship of tooth wear to chronological age among indigenous Amazon
      populations.
AB  - In indigenous populations, age can be estimated based on family structure and
      physical examination. However, the accuracy of such methods is questionable. The
      aim of this cross-sectional study was to evaluate occlusal tooth wear related to
      estimated age in the remote indigenous populations of the Xingu River, Amazon.
      Two hundred and twenty three semi-isolated indigenous subjects with permanent
      dentition from the Arara (n = 117), Xicrin-Kayapo (n = 60) and Assurini (n = 46)
      villages were examined. The control group consisted of 40 non-indigenous
      individuals living in an urban area in the Amazon basin (Belem). A modified tooth
      wear index was applied and then associated with chronological age by linear
      regression analysis. A strong association was found between tooth wear and
      chronological age in the indigenous populations (p <0.001). Tooth wear
      measurements were able to explain 86% of the variation in the ages of the Arara
      sample, 70% of the Xicrin-Kaiapo sample and 65% of the Assurini sample. In the
      urban control sample, only 12% of ages could be determined by tooth wear. These
      findings suggest that tooth wear is a poor estimator of chronological age in the
      urban population; however, it has a strong association with age for the more
      remote indigenous populations. Consequently, these findings suggest that a simple
      tooth wear evaluation method, as described and applied in this study, can be used
      to provide a straightforward and efficient means to assist in age determination
      of newly contacted indigenous groups. 

PMID- 25602502
TI  - Racial/ethnic differences in parent-reported barriers to accessing children's
      health services.
AB  - The goals of this study were to identify whether barriers that parents perceived
      to using health care differed by service type (medical vs. mental health care)
      and whether there were racial/ethnic differences in barriers. Participants were a
      community sample of 275 parents (34.2% African American, 36.7% Caucasian, and
      29.1% Hispanic) of children ages 9-13 years old who rated the extent to which
      potential barriers in 3 broad domains (stigma-related, logistical, and
      socioeconomic) would prevent or delay them from obtaining services. They also
      rated internalizing and externalizing problems exhibited by their child. Overall,
      parents reported greater socioeconomic and stigma-related barriers to obtaining
      mental health services than medical services. Hispanic parents reported
      socioeconomic and stigma-related barriers as more inhibiting than did African
      American parents. Findings highlight the importance of strengthening
      relationships between mental health care providers and the community to reduce
      the stigma associated with seeking mental health treatment for children and
      better educating parents about the potential benefits of treatment. Policy
      focused on educating parents about their insurance options and improving
      insurance coverage may help to reduce socioeconomic barriers.

PMID- 25602503
TI  - Using telepsychology to provide a group parenting program: A preliminary
      evaluation of effectiveness.
AB  - Telepsychology offers the potential to reach rural and underserved children and
      families with mental health concerns. The current study evaluated the effects of
      using videoconferencing technology to deliver an evidence-based parenting
      program, the Group Triple P Positive Parenting Program (Group Triple P; Turner,
      Markie-Dadds, & Sanders, 2002), with families who had a child experiencing
      behavioral problems. Using a pre/post design, families (N = 13) from low
      socioeconomic backgrounds in Kentucky completed the Group Triple P via a
      videoconferencing delivery format. A benchmarking strategy (Weersing & Hamilton,
      2005) indicated that treatment effect sizes for the videoconferencing format were
      generally comparable to treatment effect sizes for Group Triple P studies
      conducted in-person. Specifically, child behavior and parenting outcomes were
      similar across delivery formats. Implications of the study's findings and future
      directions for telepsychology research and practice with underserved families and
      children are discussed.

PMID- 25602504
TI  - The relationship between stigma and self-reported willingness to use mental
      health services among rural and urban older adults.
AB  - The large number of rural older adults suffering from untreated psychiatric
      illnesses suggests that stigma may be a significant barrier to the utilization of
      mental health services in this population. The current study examines self
      stigma, public stigma, and attitudes toward specialty mental health care in a
      community sample of older adults living in a geographically isolated rural area,
      a rural area adjacent to a metropolitan area, and an urban area. One hundred and
      29 older adults age 60 and above from the 3 geographic areas completed self
      report measures of these constructs, and differences on the measures were
      assessed among the groups. Results indicated that older adults living in isolated
      rural counties demonstrated higher levels of public and self-stigma and lower
      levels of psychological openness than older adults in urban areas even after
      accounting for education, employment, and income. However, no differences emerged
      in reported willingness to use specialized mental health care in the event of
      significant distress. Results are discussed in the context of rural values,
      beliefs, and community structural factors. We further suggest that conventional
      binary rural/urban distinctions are not sufficient to understand the relationship
      between rurality and stigma.

PMID- 25602505
TI  - Folic acid-conjugated europium complexes as luminescent probes for selective
      targeting of cancer cells.
AB  - We report the synthesis of three optical probes (Eu(3+)?1, Eu(3+)?2, and
      Eu(3+)?3) having a luminescent Eu complex (signaling unit) bonded in different
      positions to folic acid (FA), the folate receptor (FR) targeting unit. The
      structures of the two regioisomers Eu(3+)?1 and Eu(3+)?2 were assigned by mass
      spectrometric experiments. The optical properties and stability of these probes
      were assessed in phosphate-buffered saline, cell culture medium, rat serum, and
      cellular lysate, and results indicated that they are chemically and
      photophysically stable. Cytotoxicity was studied with ovarian cancer cells having
      high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression
      of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells,
      was in the order Eu(3+)?2 > Eu(3+)?1 > Eu(3+)?3. No internalization was observed
      for A2780 cells. Such results, together with those obtained in competition
      experiments of FA versus Eu(3+)?2 and FA or Eu(3+)?2 versus (3)H-FA, indicate
      that internalization is receptor-mediated and that Eu(3+)?2 shows high
      selectivity and specificity for FR. 

PMID- 25602507
TI  - Parkinson Disease: Diffusion MR Imaging to Detect Nigrostriatal Pathway Loss in a
      Marmoset Model Treated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AB  - PURPOSE: To investigate the use of diffusion-tensor imaging (DTI) to detect
      denervation of the nigrostriatal pathway in a nonhuman primate model of Parkinson
      disease (PD) after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). MATERIALS AND METHODS: This study was approved by the institutional
      committee for animal experiments. DTI was performed in marmosets (n = 6) by using
      a 7-T magnetic resonance (MR) imager before and 10 weeks after administration of
      MPTP. Fixed brains of a normal marmoset and a marmoset model of PD (n = 1) were
      analyzed by using microscopic tractography. Tyrosine-hydroxylase staining of
      dopaminergic neurons and three-dimensional histologic analysis also were
      performed in normal marmosets (n = 2) and a PD marmoset model (n = 2) to validate
      the course of the nigrostriatal pathway revealed at tractography. Statistical
      analysis of voxel-based and post hoc region-of-interest analyses of DTI maps was
      performed by using a paired t test. RESULTS: At voxel-based analysis of DTI
      before and after treatment, MPTP-treated marmoset brains showed significantly
      increased axial and radial diffusivity in the bilateral nigrostriatal pathway (P
      < .05, false discovery rate corrected). The largest area of significantly
      increased diffusivity was an area of axial diffusivity in the right hemispere
      (177 mm(3)) that corresponded to the location of dopaminergic neurodegeneration
      at histologic evaluation. Region-of-interest analysis revealed a 27% increase in
      axial diffusivity in the right hemisphere (1.198 mm(2)/sec +/- 0.111 to 1.522
      mm(2)/sec +/- 0.118; P = .002). Three-dimensional histologic analysis with
      tyrosine-hydroxylase staining showed the course of the nigrostriatal pathway and
      degeneration in the PD marmoset model as the absence of a tyrosine-hydroxylase
      stained region. Microscopic tractography showed that the connection of the
      substantia nigra to the striatum followed the same course as the nigrostriatal
      pathway and fewer fiber tracts in the PD marmoset model. CONCLUSION: DTI and
      microscopic tractography showed the loss of fiber structures of the nigrostriatal
      pathway in the marmoset model of PD. The results of this study provide a
      potential basis for the use of DTI in the clinical diagnosis of PD.

PMID- 25602511
TI  - Temperature-sensitive fluorescent organic nanoparticles with aggregation-induced
      emission for long-term cellular tracing.
AB  - Temperature-sensitive organic nanoparticles with AIE effect were assembled in
      water from tetraphenylethene-based poly(N-isopropylacrylamide) (TPE-PNIPAM),
      which was synthesized by ATRP using TPE derivative as initiator. The size and
      fluorescence of TPE-PNIPAM nanoparticles can be tuned by varying the temperature.
      These nanoparticles can be internalized readily by HeLa cells and can be used as
      long-term tracer in live cells to be retained for as long as seven passages. 

PMID- 25602506
TI  - RecQ4 promotes the conversion of the pre-initiation complex at a site-specific
      origin for DNA unwinding in Xenopus egg extracts.
AB  - Eukaryotic DNA replication is initiated through stepwise assembly of
      evolutionarily conserved replication proteins onto replication origins, but how
      the origin DNA is unwound during the assembly process remains elusive. Here, we
      established a site-specific origin on a plasmid DNA, using in vitro replication
      systems derived from Xenopus egg extracts. We found that the pre-replicative
      complex (pre-RC) was preferentially assembled in the vicinity of GAL4 DNA-binding
      sites of the plasmid, depending on the binding of Cdc6 fused with a GAL4 DNA
      binding domain in Cdc6-depleted extracts. Subsequent addition of nucleoplasmic S
      phase extracts to the GAL4-dependent pre-RC promoted initiation of DNA
      replication from the origin, and components of the pre-initiation complex (pre
      IC) and the replisome were recruited to the origin concomitant with origin
      unwinding. In this replication system, RecQ4 is dispensable for both recruitment
      of Cdc45 onto the origin and stable binding of Cdc45 and GINS to the pre-RC
      assembled plasmid. However, both origin binding of DNA polymerase alpha and
      unwinding of DNA were diminished upon depletion of RecQ4 from the extracts. These
      results suggest that RecQ4 plays an important role in the conversion of pre-ICs
      into active replisomes requiring the unwinding of origin DNA in vertebrates. 

PMID- 25602513
TI  - Template-free synthesis of hollow-structured Co3O4 nanoparticles as high
      performance anodes for lithium-ion batteries.
AB  - We have developed a template-free procedure to synthesize Co3O4 hollow-structured
      nanoparticles on a Vulcan XC-72 carbon support. The material was synthesized via
      an impregnation-reduction method followed by air oxidation. In contrast to
      spherical particles, the hollow-structured Co3O4 nanoparticles exhibited
      excellent lithium storage capacity, rate capability, and cycling stability when
      used as the anode material in lithium-ion batteries. Electrochemical testing
      showed that the hollow-structured Co3O4 particles delivered a stable reversible
      capacity of about 880 mAh/g (near the theoretical capacity of 890 mAh/g) at a
      current density of 50 mA/g after 50 cycles. The superior electrochemical
      performance is attributed to its unique hollow structure, which combines nano-
      and microscale properties that facilitate electron transfer and enhance
      structural robustness. 

PMID- 25602512
TI  - Observation of sGAG content of human hip joint cartilage in different old age
      groups based on EPIC micro-CT.
AB  - OBJECTIVES: To observe the age-related changes of sulfated glycosaminoglycan
      (sGAG) content of hip joint cartilage of elderly people based on Equilibrium
      Partitioning of an Ionic Contrast Agent (EPIC) micro-CT. METHODS: Seventy human
      hip cartilage-bone samples were collected from hip-fracture patients (ages 51-96)
      and divided into five groups (10 years in an age group). They were first immersed
      in 20% concentration of the contrast agent Meglumine Diatrizoate (MD) for 6 h at
      37  degrees C, and then scanned by micro-CT. Following scanning, samples were
      stained for sGAG with toluidine blue. The X-ray attenuation and sGAG optical
      density were calculated by image processing. The correlation between X-ray
      attenuation and sGAG optical density was then analyzed. RESULTS: The X-ray mean
      attenuation of the cartilage increased by 18.81% from the 50-80 age groups (p <
      0.01), but decreased by 7.15% in the 90 age group compared to the 80 age group.
      The X-ray mean attenuation of the superficial layer and middle layer increased by
      31.60 % and 44.68% from the 50-80 age groups, respectively (p < 0.01), but
      reduced by 4.67% and 6.05% separately in the 90 age group. However, the deep
      layer showed no significant change with aging. The sGAG optical density showed a
      linear correlation (r = -0.91, p < 0.01) with the X-ray attenuation. CONCLUSION:
      The sGAG content of hip joint cartilage varied with aging in elderly people. The
      changes in superficial layer and middle layer were more evident than deep layer.

PMID- 25602515
TI  - Simulation of human atherosclerotic femoral plaque tissue: the influence of
      plaque material model on numerical results.
AB  - BACKGROUND: Due to the limited number of experimental studies that mechanically
      characterise human atherosclerotic plaque tissue from the femoral arteries, a
      recent trend has emerged in current literature whereby one set of material data
      based on aortic plaque tissue is employed to numerically represent diseased
      femoral artery tissue. This study aims to generate novel vessel-appropriate
      material models for femoral plaque tissue and assess the influence of using
      material models based on experimental data generated from aortic plaque testing
      to represent diseased femoral arterial tissue. METHODS: Novel material models
      based on experimental data generated from testing of atherosclerotic femoral
      artery tissue are developed and a computational analysis of the revascularisation
      of a quarter model idealised diseased femoral artery from a 90% diameter stenosis
      to a 10% diameter stenosis is performed using these novel material models. The
      simulation is also performed using material models based on experimental data
      obtained from aortic plaque testing in order to examine the effect of employing
      vessel appropriate material models versus those currently employed in literature
      to represent femoral plaque tissue. RESULTS: Simulations that employ material
      models based on atherosclerotic aortic tissue exhibit much higher maximum
      principal stresses within the plaque than simulations that employ material models
      based on atherosclerotic femoral tissue. Specifically, employing a material model
      based on calcified aortic tissue, instead of one based on heavily calcified
      femoral tissue, to represent diseased femoral arterial vessels results in a 487
      fold increase in maximum principal stress within the plaque at a depth of 0.8 mm
      from the lumen. CONCLUSIONS: Large differences are induced on numerical results
      as a consequence of employing material models based on aortic plaque, in place of
      material models based on femoral plaque, to represent a diseased femoral vessel.
      Due to these large discrepancies, future studies should seek to employ vessel
      appropriate material models to simulate the response of diseased femoral tissue
      in order to obtain the most accurate numerical results.

PMID- 25602514
TI  - Combined sub-optimal doses of rosuvastatin and bexarotene impair angiotensin II
      induced arterial mononuclear cell adhesion through inhibition of Nox5 signaling
      pathways and increased RXR/PPARalpha and RXR/PPARgamma interactions.
AB  - AIM: Mononuclear cell (MC) infiltration into the arterial subendothelium is a key
      event in atherogenesis. Rosuvastatin (Rosu) and bexarotene (Bex) exert anti
      inflammatory activity, but serious dose-related adverse effects have emerged. The
      need for safer and effective strategies to prevent and treat atherosclerosis led
      us to test the effect of combined use of both drugs on angiotensin II (Ang-II)
      induced arterial MC recruitment. RESULTS: Vehicle, Rosu (10-30 nM), Bex (0.3-1
      MUM), or a combination of both were administered to human umbilical arterial
      endothelial cells (HUAECs) 20 h before stimulation with 1 MUM Ang-II (4 h).
      Surprisingly, a combination of Rosu (10 nM)+Bex (0.3 MUM), which did not
      influence Ang-II-induced MC recruitment when either stimulus was studied alone,
      significantly reduced this response. This effect was accompanied by diminished
      Ang-II-induced ICAM-1, VCAM-1, and CX3CL1 endothelial expression and CXCL1,
      CXCL8, CCL2, and CCL5 production. Preincubation of HUAECs with Rosu+Bex inhibited
      Nox5 expression and Nox5-induced RhoA activation stimulated by Ang-II through
      increased RXRalpha, PPARalpha, and PPARgamma expression in addition to
      RXRalpha/PPARalpha and RXRalpha/PPARgamma interactions. In vivo, combined but not
      single administration of Rosu (1.25 mg/kg/day) and Bex (10 mg/kg/day)
      significantly diminished Ang-II-induced arteriolar leukocyte adhesion in the
      cremasteric microcirculation of C57BL/6 mice and atherosclerotic lesion formation
      in apoE(-/-) mice subjected to an atherogenic diet. INNOVATION AND CONCLUSION:
      Combined administration of Bex+Rosu at suboptimal doses may constitute a new
      alternative and effective therapy in the control of the vascular inflammation
      associated to cardiometabolic disorders, since they synergize in their anti
      inflammatory actions and may counteract their associated adverse effects.

PMID- 25602516
TI  - Contrast-induced acute kidney injury: potential new strategies.
AB  - PURPOSE OF REVIEW: Contrast-induced acute kidney injury (CI-AKI) is an impairment
      of renal function following contrast media administration in the absence of an
      alternative cause. It represents a powerful predictor of poor early and late
      outcomes. Here, we review the major strategies to prevent CI-AKI. RECENT
      FINDINGS: Hydration represents the gold standard as a prophylactic measure to
      prevent CI-AKI, acting by increasing urine flow rate and, thereby, by limiting
      the time of contact between the contrast media and the tubular epithelial cells.
      An optimal hydration regimen should be defined according to predefined clinical
      markers, such as urine flow rate, or left ventricular end-diastolic pressure.
      Recently, high-dose statins pretreatment has been included in the guidelines of
      CI-AKI prevention. However, uncertainty still exists on the efficacy of several
      compounds tested in both observational trials and randomized studies to prevent
      CI-AKI. Compounds evaluated include diuretics (furosemide), antioxidants (i.e. N
      acetylcysteine and statins) and vasodilators (i.e. calcium antagonists, dopamine
      and fenoldopam). SUMMARY: Hydration still represents the most reliable strategy
      to prevent CI-AKI. New prophylactic strategies for acute kidney injury are still
      under investigation.

PMID- 25602517
TI  - NEDD4-2 and salt-sensitive hypertension.
AB  - PURPOSE OF REVIEW: NEDD4-2 is an ubiquitin-protein ligase that was originally
      identified as an interactor of the epithelial Na+ channel (ENaC); this
      interaction is defective in Liddle's syndrome, causing elevated ENaC activity and
      salt-sensitive hypertension. In this review we aim to highlight progress achieved
      in recent years demonstrating that NEDD4-2 is involved in the control of Na+
      transporters that are different from ENaC, but which also play a role in salt
      sensitive hypertension. RECENT FINDINGS: It has been shown that NEDD4-2 interacts
      with ubiquitylates and negatively regulates the thiazide-sensitive NCC (Na+,Cl- 
      cotransporter), both in vitro and in vivo in inducible, nephron-specific Nedd4-2
      knockout mice. Moreover, evidence has been provided that NEDD4-2 is also involved
      in the regulation of human NHE3 (Na+,H+-exchanger 3) and NKCC2 (Na+,K+,2Cl- 
      cotransporter 2). SUMMARY: The emerging role of NEDD4-2 in the regulation of
      different Na+ transporters along the nephron and the identification of human
      polymorphisms in the NEDD4-2 gene (Nedd4L) related to salt-sensitive hypertension
      makes this ubiquitin-protein ligase an interesting target for the development of
      antihypertensive drugs.

PMID- 25602518
TI  - Mutation spectrum of RB1 gene in unilateral retinoblastoma cases from Tunisia and
      correlations with clinical features.
AB  - Retinoblastoma, an embryonic neoplasm of retinal origin, is the most common
      primary intraocular malignancy in children. Somatic inactivation of both alleles
      of the RB1 tumor suppressor gene in a retinal progenitor cell through diverse
      mechanisms including genetic and epigenetic modifications, is the crucial event
      in initiation of tumorigenesis in most cases of isolated unilateral
      retinoblastoma. We analyzed DNA from tumor tissue and from peripheral blood to
      determine the RB1 mutation status and seek correlations with clinical features of
      37 unrelated cases of Tunisian origin with sporadic retinoblastoma. All cases
      were unilateral except one who presented with bilateral disease, in whom no
      germline coding sequence alteration was identified. A multi-step mutation
      scanning protocol identified bi-allelic inactivation of RB1 gene in 30 (81%) of
      the samples tested. A total of 7 novel mutations were identified. There were
      three tumors without any detectable mutation while a subset contained multiple
      mutations in RB1 gene. The latter group included tumors collected after treatment
      with chemotherapy. There were seven individuals with germline mutations and all
      presented with advanced stage of tumor. There was no difference in age of onset
      of RB based on the germline mutation status. Thus 20% of the individuals with
      sporadic unilateral RB in this series carried germline mutations and indicate the
      importance of genetic testing all children with sporadic retinoblastoma. These
      findings help to characterize the spectrum of mutations present in the Tunisian
      population and can improve genetic diagnosis of retinoblastoma. 

PMID- 25602519
TI  - CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly
      factor I with chromatin.
AB  - Chromatin Assembly Factor I (CAF-I) plays a key role in the replication-coupled
      assembly of nucleosomes. It is expected that its function is linked to the
      regulation of the cell cycle, but little detail is available. Current models
      suggest that CAF-I is recruited to replication forks and to chromatin via an
      interaction between its Cac1p subunit and the replication sliding clamp, PCNA,
      and that this interaction is stimulated by the kinase CDC7. Here we show that
      another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S
      phase and regulates its association with chromatin, but not its association with
      PCNA. Mutations in the Cac1p-phosphorylation sites of CDC28 but not of CDC7
      substantially reduce the in vivo phosphorylation of Cac1p. However, mutations in
      the putative CDC7 target sites on Cac1p reduce its stability. The association of
      CAF-I with chromatin is impaired in a cdc28-1 mutant and to a lesser extent in a
      cdc7-1 mutant. In addition, mutations in the Cac1p-phosphorylation sites by both
      CDC28 and CDC7 reduce gene silencing at the telomeres. We propose that this
      phosphorylation represents a regulatory step in the recruitment of CAF-I to
      chromatin in early S phase that is distinct from the association of CAF-I with
      PCNA. Hence, we implicate CDC28 in the regulation of chromatin reassembly during
      DNA replication. These findings provide novel mechanistic insights on the links
      between cell-cycle regulation, DNA replication and chromatin reassembly. 

PMID- 25602520
TI  - RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates
      ATR-Chk1 signaling.
AB  - The ATR-Chk1 signaling pathway mediates cellular responses to DNA damage and
      replication stress and is composed of a number of core factors that are conserved
      throughout eukaryotic organisms. However, humans and other higher eukaryotic
      species possess additional factors that are implicated in the regulation of this
      signaling network but that have not been extensively studied. Here we show that
      RHINO (for Rad9, Rad1, Hus1 interacting nuclear orphan) forms complexes with both
      the 9-1-1 checkpoint clamp and TopBP1 in human cells even in the absence of
      treatments with DNA damaging agents via direct interactions with the Rad9 and
      Rad1 subunits of the 9-1-1 checkpoint clamp and with the ATR kinase activator
      TopBP1. The interaction of RHINO with 9-1-1 was of sufficient affinity to allow
      for the purification of a stable heterotetrameric RHINO-Rad9-Hus1-Rad1 complex in
      vitro. In human cells, a portion of RHINO localizes to chromatin in the absence
      of DNA damage, and this association is enriched following UV irradiation.
      Furthermore, we find that the tethering of a Lac Repressor (LacR)-RHINO fusion
      protein to LacO repeats in chromatin of mammalian cells induces Chk1
      phosphorylation in a Rad9- and Claspin-dependent manner. Lastly, the loss of
      RHINO partially abrogates ATR-Chk1 signaling following UV irradiation without
      impacting the interaction of the 9-1-1 clamp with TopBP1 or the loading of 9-1-1
      onto chromatin. We conclude that RHINO is a bona fide regulator of ATR-Chk1
      signaling in mammalian cells. 

PMID- 25602521
TI  - RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative
      breast cancer.
AB  - Triple negative breast cancer (TNBC) is characterized by multiple genetic events
      occurring in concert to drive pathogenic features of the disease. Here we
      interrogated the coordinate impact of p53, RB, and MYC in a genetic model of
      TNBC, in parallel with the analysis of clinical specimens. Primary mouse mammary
      epithelial cells (mMEC) with defined genetic features were used to delineate the
      combined action of RB and/or p53 in the genesis of TNBC. In this context, the
      deletion of either RB or p53 alone and in combination increased the proliferation
      of mMEC; however, the cells did not have the capacity to invade in matrigel. Gene
      expression profiling revealed that loss of each tumor suppressor has effects
      related to proliferation, but RB loss in particular leads to alterations in gene
      expression associated with the epithelial-to-mesenchymal transition. The
      overexpression of MYC in combination with p53 loss or combined RB/p53 loss drove
      rapid cell growth. While the effects of MYC overexpression had a dominant impact
      on gene expression, loss of RB further enhanced the deregulation of a gene
      expression signature associated with invasion. Specific RB loss lead to enhanced
      invasion in boyden chambers assays and gave rise to tumors with minimal
      epithelial characteristics relative to RB-proficient models. Therapeutic
      screening revealed that RB-deficient cells were particularly resistant to agents
      targeting PI3K and MEK pathway. Consistent with the aggressive behavior of the
      preclinical models of MYC overexpression and RB loss, human TNBC tumors that
      express high levels of MYC and are devoid of RB have a particularly poor outcome.
      Together these results underscore the potency of tumor suppressor pathways in
      specifying the biology of breast cancer. Further, they demonstrate that MYC
      overexpression in concert with RB can promote a particularly aggressive form of
      TNBC. 

PMID- 25602522
TI  - The impact of the HIRA histone chaperone upon global nucleosome architecture.
AB  - HIRA is an evolutionarily conserved histone chaperone that mediates replication
      independent nucleosome assembly and is important for a variety of processes such
      as cell cycle progression, development, and senescence. Here we have used a
      chromatin sequencing approach to determine the genome-wide contribution of HIRA
      to nucleosome organization in Schizosaccharomyces pombe. Cells lacking HIRA
      experience a global reduction in nucleosome occupancy at gene sequences,
      consistent with the proposed role for HIRA in chromatin reassembly behind
      elongating RNA polymerase II. In addition, we find that at its target promoters,
      HIRA commonly maintains the full occupancy of the -1 nucleosome. HIRA does not
      affect global chromatin structure at replication origins or in rDNA repeats but
      is required for nucleosome occupancy in silent regions of the genome. Nucleosome
      organization associated with the heterochromatic (dg-dh) repeats located at the
      centromere is perturbed by loss of HIRA function and furthermore HIRA is required
      for normal nucleosome occupancy at Tf2 LTR retrotransposons. Overall, our data
      indicate that HIRA plays an important role in maintaining nucleosome architecture
      at both euchromatic and heterochromatic loci. 

PMID- 25602523
TI  - Patterning in time and space: HoxB cluster gene expression in the developing
      chick embryo.
AB  - The developing embryo is a paradigmatic model to study molecular mechanisms of
      time control in Biology. Hox genes are key players in the specification of tissue
      identity during embryo development and their expression is under strict temporal
      regulation. However, the molecular mechanisms underlying timely Hox activation in
      the early embryo remain unknown. This is hindered by the lack of a rigorous
      temporal framework of sequential Hox expression within a single cluster. Herein,
      a thorough characterization of HoxB cluster gene expression was performed over
      time and space in the early chick embryo. Clear temporal collinearity of HoxB
      cluster gene expression activation was observed. Spatial collinearity of HoxB
      expression was evidenced in different stages of development and in multiple
      tissues. Using embryo explant cultures we showed that HoxB2 is cyclically
      expressed in the rostral presomitic mesoderm with the same periodicity as somite
      formation, suggesting a link between timely tissue specification and somite
      formation. We foresee that the molecular framework herein provided will
      facilitate experimental approaches aimed at identifying the regulatory mechanisms
      underlying Hox expression in Time and Space. 

PMID- 25602525
TI  - Regioselective synthesis of tetraphenyl-1,3-butadienes with aggregation-induced
      emission.
AB  - In the presence of substoichiometric amounts of Co2(CO)8, internal bisarylalkynes
      undergo reductive dimerization with good to excellent yields. The Co2(CO)8
      induced reactions described are experimentally quite simple and provide a very
      useful synthetic procedure for the synthesis of tetraphenylbutadienes which
      exhibit aggregation-induced emission enhancement, i.e., weak emission in good
      solvents but strong fluorescence in solvents that lead toward formation of
      aggregates or in the solid state. 

PMID- 25602524
TI  - Characterization of TAZ domains important for the induction of breast cancer stem
      cell properties and tumorigenesis.
AB  - The Hippo pathway is an evolutionarily conserved regulator of tissue growth and
      cell fate during development and regeneration. Conversely, deregulation of the
      Hippo pathway has been reported in several malignancies. Here, we used
      integrative functional genomics approaches to identify TAZ, a transcription co
      activator and key downstream effector of the Hippo pathway, as an essential
      driver for the propagation of TNBC malignant phenotype. We further showed in non
      transformed human mammary basal epithelial cells that expression of
      constitutively active TAZ confers cancer stem cell (CSC) traits that are
      dependent on the TAZ and TEAD interacting domains. In addition, to gain a better
      understanding of how TAZ functions, we performed genetic-function analysis of
      TAZ. Significantly, we identified that both the WW and transcriptional activation
      domains of TAZ are critical for the induced CSC properties as well as tumorigenic
      potential as manifested in vitro and in human breast cancer xenograft in vivo.
      Collectively, our data suggest that pharmacological inhibition of TAZ activity
      may provide a novel means of targeting and eliminating breast CSCs. 

PMID- 25602526
TI  - Illegal drug use among female university students in Slovakia.
AB  - BACKGROUND: This study is focused on the issue of illegal drug use among female
      university students preparing to become teachers. The main aim was to determine
      the frequency of drug abuse in a group of young women (n=215, mean age 20.44
      years). MATERIAL/METHODS: Using survey methods, we determined that 33.48% of
      female university students in Slovakia use illegal drugs and 66.51% of students
      have never used illegal drugs. Differences between these groups were determined
      using statistical analysis, mostly in 4 areas of survey questions. RESULTS: We
      determined that education of parents has a statistically significant influence on
      use of illegal drugs by their children (chi2=10.14; P<0.05). Communication
      between parents and children and parental attention to children have a
      significant role in determining risky behavior (illegal drug use, chi2=8.698,
      P<0.05). Parents of students not using illegal drugs were interested in how their
      children spend their free time (68.53%). We confirmed the relationship between
      consumption of alcohol and illegal drug use (chi2=16.645; P<0.001) and smoking
      (chi2=6.226; P<0.05). The first contact with drugs occurs most frequently at high
      school age. The most consumed "soft" drug in our group of female university
      students is marijuana. CONCLUSIONS: Our findings are relevant for comparison and
      generalization regarding causes of the steady increase in number of young people
      using illegal drugs.

PMID- 25602529
TI  - Interaction of C60 with water: first-principles modeling and environmental
      implications.
AB  - The nature of fullerene-water interactions has been the subject of much research
      and debate. Specifically, the presence of a stabilizing, negative surface
      potential on colloidal aggregates of C60 in water is unexpected, given the
      neutral nature of pure carbon, and is not well understood. Previous simulation
      efforts have focused on the C60-water interaction using molecular dynamics
      simulations that lacked the ability to account for charge transfer and
      distribution interactions. In this study, first-principles density functional
      theory was used to analyze the fundamental electronic interactions to elucidate
      the polarization and charge transfer between water and C60. Simulations show that
      charge is inductively transferred to the C60 from water molecules, with
      subsequent polarization of the C60 molecule. In a case with two neighboring C60
      molecules, the charge polarization induces a charge onto the second C60.
      Simulation suggests that this charge transfer and polarization may contribute at
      least partly to the observed negative surface potential of fullerene aggregates
      and, combined with hydrogen bonding network formation around C60, provides a
      fundamental driving force for aggregate formation in water. 

PMID- 25602527
TI  - The watering of tall trees--embolization and recovery.
AB  - We can propound a thermo-mechanical understanding of the ascent of sap to the top
      of tall trees thanks to a comparison between experiments associated with the
      cohesion-tension theory and the disjoining pressure concept for liquid thin
      films. When a segment of xylem is tight-filled with crude sap, the liquid
      pressure can be negative although the pressure in embolized vessels remains
      positive. Examples are given that illustrate how embolized vessels can be
      refilled and why the ascent of sap is possible even in the tallest trees avoiding
      the problem due to cavitation. However, the maximum height of trees is limited by
      the stability domain of liquid thin-films. 

PMID- 25602530
TI  - The rs13064411 polymorphism in the WDR52 gene, associated with PCSK9 levels,
      modifies statin-induced changes in serum total and LDL cholesterol levels.
AB  - OBJECTIVE: Recently, the minor allele of the rs13064411A>G polymorphism in the WD
      repeat domain 52 (WDR52) gene was associated with increased statin-induced
      proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and with LDL
      cholesterol response to statins. PCSK9 promotes LDL receptor degradation, leading
      to increased serum LDL cholesterol. We investigated whether the polymorphism was
      associated with cholesterol response to statins. METHODS: We identified 1105
      current, 322 past, and 4831 never statin users during follow-up in the
      prospective population-based Rotterdam Study. The mean delta total, LDL, and HDL
      cholesterol levels between current and no current statin users with the same
      number of minor alleles were analyzed using random-effect repeated measurements.
      We adjusted for age, sex, number of cholesterol measurements, and follow-up time.
      RESULTS: Compared with no users with the same genotype, current statin users
      carrying a minor allele showed a statistically significantly lower delta total
      and LDL cholesterol compared with reference homozygous major allele carriers
      [total: Delta=0.551 mmol/l (AG+GG) vs. Delta=0.732 mmol/l (AA), Pinteraction:
      5.2*10(-7); LDL: Delta=0.566 mmol/l (AG+GG) vs. Delta=0.720 mmol/l (AA),
      Pinteraction: 1.8*10(-5)]. The effect was stronger in women (Pinteraction:
      2.0*10(-5) for LDL cholesterol, 8.0*10(-6) for total cholesterol) and in high
      dose users (defined daily doses>1.00) (Pinteraction: 7.0*10(-5) for LDL
      cholesterol, Pinteraction: 0.081 for total cholesterol). The polymorphism was not
      associated with HDL cholesterol in current statin users, or with total, LDL and
      HDL cholesterol in never statin users. CONCLUSION: The minor G allele of the
      rs13064411 polymorphism, associated with statin-induced PCSK9-levels, was
      associated with a decreased LDL-lowering and total cholesterol-lowering response
      to statins.

PMID- 25602531
TI  - Limited efficacy of platinum-based adjuvant treatment on the outcome of
      borderline ovarian tumors.
AB  - Adjuvant treatment of borderline ovarian tumors (BOT) remains highly debatable.
      This article evaluates the benefits of platinum-based adjuvant treatment in
      patients with BOT. The PubMed and Cochrane Library databases were systematically
      searched for articles using the terms ((Borderline) OR (low malignant potential)
      AND (ovarian)) AND ((tumor) OR (cancer)) AND ((follow-up) OR (survival) OR
      (treatment) OR (chemotherapy) OR (adjuvant treatment)). We identified 31 articles
      including 4965 patients. Together, 592 patients presented non-invasive-, 244
      invasive- and 77 unspecified implants. Central pathological examination was
      performed in 23 studies. Nine studies included more than 90% stage I patients,
      while 11 included only advanced stage patients. Nineteen studies reported
      patients undergoing complete cytoreduction, ten reported response rates and eight
      compared survival outcomes. All studies provided information regarding either
      mortality or recurrence rates. A meta-analysis of the 13 studies providing
      separate mortality data for both treatment groups, including 2206 women, favored
      surgical treatment only (OR=7.44; 95% CI=3.39-16.32; p<0.0005) albeit with
      moderate heterogeneity of the studies (I(2)=35.0%) but no asymmetry (Egger's test
      p=0.44). Regarding survival data, 4 studies reported no difference between
      groups. In the adjuvant setting, 4 reported worse outcome and 1 reported a
      nonsignificant trend to worse outcome. At present, there is no evidence to
      support the use of adjuvant treatment in patients with BOT. 

PMID- 25602532
TI  - A method of extending the depth of focus of the high-resolution X-ray imaging
      system employing optical lens and scintillator: a phantom study.
AB  - BACKGROUND: The high-resolution X-ray imaging system employing synchrotron
      radiation source, thin scintillator, optical lens and advanced CCD camera can
      achieve a resolution in the range of tens of nanometers to sub-micrometer. Based
      on this advantage, it can effectively image tissues, cells and many other small
      samples, especially the calcification in the vascular or in the glomerulus. In
      general, the thickness of the scintillator should be several micrometers or even
      within nanometers because it has a big relationship with the resolution. However,
      it is difficult to make the scintillator so thin, and additionally thin
      scintillator may greatly reduce the efficiency of collecting photons. METHODS: In
      this paper, we propose an approach to extend the depth of focus (DOF) to solve
      these problems. We develop equation sets by deducing the relationship between the
      high-resolution image generated by the scintillator and the degraded blur image
      due to defect of focus first, and then we adopt projection onto convex sets
      (POCS) and total variation algorithm to get the solution of the equation sets and
      to recover the blur image. RESULTS: By using a 20 MUm thick unmatching
      scintillator to replace the 1 MUm thick matching one, we simulated a high
      resolution X-ray imaging system and got a degraded blur image. Based on the
      algorithm proposed, we recovered the blur image and the result in the experiment
      showed that the proposed algorithm has good performance on the recovery of image
      blur caused by unmatching thickness of scintillator. CONCLUSIONS: The method
      proposed is testified to be able to efficiently recover the degraded image due to
      defect of focus. But, the quality of the recovery image especially of the low
      contrast image depends on the noise level of the degraded blur image, so there is
      room for improving and the corresponding denoising algorithm is worthy for
      further study and discussion.

PMID- 25602534
TI  - Applications of the SWAT Model Special Section: Overview and Insights.
AB  - The Soil and Water Assessment Tool (SWAT) model has emerged as one of the most
      widely used water quality watershed- and river basin-scale models worldwide,
      applied extensively for a broad range of hydrologic and/or environmental
      problems. The international use of SWAT can be attributed to its flexibility in
      addressing water resource problems, extensive networking via dozens of training
      workshops and the several international conferences that have been held during
      the past decade, comprehensive online documentation and supporting software, and
      an open source code that can be adapted by model users for specific application
      needs. The catalyst for this special collection of papers was the 2011
      International SWAT Conference & Workshops held in Toledo, Spain, which featured
      over 160 scientific presentations representing SWAT applications in 37 countries.
      This special collection presents 22 specific SWAT-related studies, most of which
      were presented at the 2011 SWAT Conference; it represents SWAT applications on
      five different continents, with the majority of studies being conducted in Europe
      and North America. The papers cover a variety of topics, including hydrologic
      testing at a wide range of watershed scales, transport of pollutants in northern
      European lowland watersheds, data input and routing method effects on sediment
      transport, development and testing of potential new model algorithms, and
      description and testing of supporting software. In this introduction to the
      special section, we provide a synthesis of these studies within four main
      categories: (i) hydrologic foundations, (ii) sediment transport and routing
      analyses, (iii) nutrient and pesticide transport, and (iv) scenario analyses. We
      conclude with a brief summary of key SWAT research and development needs. 

PMID- 25602533
TI  - Using health and demographic surveillance system (HDSS) data to analyze
      geographical distribution of socio-economic status; an experience from KEMRI/CDC
      HDSS.
AB  - Continuous monitoring in health and demographic surveillance sites (HDSS) allows
      for collection of longitudinal demographic data, health related, and socio
      economic indicators of the site population. We sought to use household survey
      data collected between 2002 and 2006 in the Kenya Medical Research Institute in
      collaboration with Centers for Disease Control and prevention (KEMRI/CDC) HDSS
      site in Asembo and Gem Western Kenya to estimate socio-economic status (SES) and
      assess changes of SES over time and space. Data on household assets and
      characteristics, mainly source of drinking water, cooking fuel, and occupation of
      household head was annually collected from 44,313 unique households during the
      study period. An SES index was calculated as a weighted average of assets using
      weights generated via Principal Component Analysis (PCA), Polychoric PCA, and
      Multiple Correspondence Analysis (MCA) methods applied to the pooled data. The
      index from the best method was used to rank households into SES quintiles and
      assess their transition over time across SES categories. Kriging was employed to
      produce SES maps at the start and the end of the study period. First component of
      PCA, Polychoric PCA, and MCA accounted for 13.7%, 31.8%, and 47.3%, respectively
      of the total variance of all variables. The gap between the poorest and the least
      poor increased from 1% at the start to 6% at the end of the study period. Spatial
      analysis revealed that the increase in least poor households was centered in the
      lower part of study area (Asembo) over time. No significant changes were observed
      in Gem. The HDSS sites can provide a platform to assess spatial-temporal changes
      in the SES status of the population. Evidence on how SES varied over time and
      space within the same geographical area may provide a useful tool to design
      interventions in health and other areas that have a close bearing to the SES of
      the population.

PMID- 25602535
TI  - Use of the soil and water assessment tool to scale sediment delivery from field
      to watershed in an agricultural landscape with topographic depressions.
AB  - For two watersheds in the northern Midwest United States, we show that landscape
      depressions have a significant impact on watershed hydrology and sediment yields
      and that the Soil and Water Assessment Tool (SWAT) has appropriate features to
      simulate these depressions. In our SWAT models of the Willow River in Wisconsin
      and the Sunrise River in Minnesota, we used Pond and Wetland features to capture
      runoff from about 40% of the area in each watershed. These depressions trapped
      considerable sediment, yet further reductions in sediment yield were required for
      calibration and achieved by reducing the Universal Soil Loss Equation (USLE)
      cropping-practice (P) factor to 0.40 to 0.45. We suggest terminology to describe
      annual sediment yields at different conceptual spatial scales and show how SWAT
      output can be partitioned to extract data at each of these scales. These scales
      range from plot-scale yields calculated with the USLE to watershed-scale yields
      measured at the outlet. Intermediate scales include field, upland, pre-riverine,
      and riverine scales, in descending order along the conceptual flow path from plot
      to outlet. Sediment delivery ratios, when defined as watershed-scale yields as a
      percentage of plot-scale yields, ranged from 1% for the Willow watershed (717 km)
      to 7% for the Sunrise watershed (991 km). Sediment delivery ratios calculated
      from published relations based on watershed area alone were about 5 to 6%, closer
      to pre-riverine-scale yields in our watersheds. 

PMID- 25602536
TI  - Modeling water quality to improve agricultural practices and land management in a
      tunisian catchment using the soil and water assessment tool.
AB  - Agriculture intensification has impaired water quality. In this study, the risk
      of pollution by nitrates was assessed by experimental monitoring, spatial
      integration of farm census, and modeling of water quality using the Soil and
      Water Assessment Tool (SWAT), version 2009, over the period of 1990 to 2006 for a
      catchment located northern Tunisia. Under a semiarid climate, the water quality
      is influenced by the predominating agriculture activities. The hydrological
      results are compared with the observed flows derived from measurements at the
      outlet of the Joumine watershed. Model performance showed good statistical
      agreements, with a Nash-Sutcliffe efficiency of 0.9 and a value of 0.92 after
      monthly calibration. The model predicted the timing of monthly peak flow values
      reasonably well. During the validation period, SWAT simulations were nearly as
      accurate, with Nash-Sutcliffe efficiency and values of 0.89 and 0.92,
      respectively. The model was used to simulate NO concentrations. The predicted NO
      concentration values were compared with in situ measured concentrations. The
      simulated and measured NO-N concentrations varied in the same range of 0 to 5 mg
      L at the E3 and E5 locations. The calibrated model was then used for simulating
      the impact of the best management practice scenarios to reduce NO loads to the
      river. The first set-up consisted of reducing the N fertilizer application by 20
      and 100% from the current state. These two scenarios induced a reduction in NO
      loads by 22 and 72%, respectively. The second set-up consisted of using
      vegetation filter strips. The last scenario combined filter strips and a
      reduction of 20% in N fertilizer application. Results showed NO reduction rates
      of 20 and 36%, respectively. The SWAT model allowed managers to have several
      options to improve the water quality in the Joumine watershed. 

PMID- 25602537
TI  - Sediment delivery estimates in water quality models altered by resolution and
      source of topographic data.
AB  - Moderate-resolution (30-m) digital elevation models (DEMs) are normally used to
      estimate slope for the parameterization of non-point source, process-based water
      quality models. These models, such as the Soil and Water Assessment Tool (SWAT),
      use the Universal Soil Loss Equation (USLE) and Modified USLE to estimate
      sediment loss. The slope length and steepness factor, a critical parameter in
      USLE, significantly affects sediment loss estimates. Depending on slope range, a
      twofold difference in slope estimation potentially results in as little as 50%
      change or as much as 250% change in the LS factor and subsequent sediment
      estimation. Recently, the availability of much finer-resolution (~3 m) DEMs
      derived from Light Detection and Ranging (LiDAR) data has increased. However, the
      use of these data may not always be appropriate because slope values derived from
      fine spatial resolution DEMs are usually significantly higher than slopes derived
      from coarser DEMs. This increased slope results in considerable variability in
      modeled sediment output. This paper addresses the implications of parameterizing
      models using slope values calculated from DEMs with different spatial resolutions
      (90, 30, 10, and 3 m) and sources. Overall, we observed over a 2.5-fold increase
      in slope when using a 3-m instead of a 90-m DEM, which increased modeled soil
      loss using the USLE calculation by 130%. Care should be taken when using LiDAR
      derived DEMs to parameterize water quality models because doing so can result in
      significantly higher slopes, which considerably alter modeled sediment loss. 

PMID- 25602538
TI  - Simulation of streamflow and sediment with the soil and water assessment tool in
      a data scarce catchment in the three gorges region, china.
AB  - The Three Gorges Region in China is currently subject to a large-scale land use
      change, which was induced by the construction of the Three Gorges Dam on the
      Yangtze River. The relocation of towns, villages, and agricultural areas is
      expected to affect the water balance and increase erosion rates and sediment
      yields in the affected catchments. Hydrologic and water quality models are
      frequently used to assess the impact of land use changes on water resources. In
      this study, the eco-hydrological Soil and Water Assessment Tool (SWAT) model is
      applied to the Xiangxi Catchment in the Three Gorges Region. This paper presents
      the calibration and validation of streamflow and sediment loads at Xingshan
      gauging station. The calibration of daily streamflow resulted in a satisfactory
      fit of simulated and observed data, which is indicated by Nash-Sutcliffe
      efficiency (NSE) values of 0.69 and 0.67 for the calibration (1981-1986) and
      validation (1988-1993) periods, respectively. In contrast, the model was not able
      to simulate the monthly average sediment loads correctly, as indicated by very
      low NSE values of 0.47 (calibration) and 0.08 (validation). This might be due to
      inadequate representation of spatial rainfall variability by the available
      climate stations, insufficient input data, uncertainties in the model structure,
      or uncertainties in the observed sediment loads. The discussion of these possible
      reasons for the incorrect prediction of sediment loads by SWAT reveals the need
      for further research in the field of hydrological and water quality modeling in
      China. 

PMID- 25602539
TI  - Daily nitrate losses: implication on long-term river quality in an intensive
      agricultural catchment of southwestern france.
AB  - High nitrate concentrations in streams have become a widespread problem
      throughout Europe in recent decades, damaging surface water and groundwater
      quality. The European Nitrate Directive fixed a potability threshold of 50 mg L
      for European rivers. The performance of the Soil and Water Assessment Tool model
      was assessed in the 1110-km Save catchment in southwestern France for predicting
      water discharge and nitrate loads and concentrations at the catchment outlet,
      considering observed data set uncertainty. Simulated values were compared with
      intensive and extensive measurement data sets. Daily discharge fitted
      observations (Nash-Sutcliffe efficiency coefficient = 0.61, = 0.7, and PBIAS = 
      22%). Nitrate simulation (1998-2010) was within the observed range (PBIAS = 10
      21%, considering observed data set uncertainty). Annual nitrate load at the
      catchment outlet was correlated to the annual water yield at the outlet ( =
      0.63). Simulated annual catchment nitrate exportation ranged from 21 to 49 kg ha
      depending on annual hydrological conditions (average, 36 kg ha). Exportation
      rates ranged from 3 to 8% of nitrogen inputs. During floods, 34% of the nitrate
      load was exported, which represented 18% of the 1998-2010 period. Average daily
      nitrate concentration at the outlet was 29 mg L (1998-2010), ranging from 0 to
      270 mg L. Nitrate concentration exceeded the European 50 mg L potability
      threshold during 244 d between 1998 and 2010. A 20% reduction of nitrogen input
      reduced crop yield by between 5 and 9% and reduced by 62% the days when the 50 mg
      L threshold was exceeded. 

PMID- 25602540
TI  - Simulating Landscape Sediment Transport Capacity by Using a Modified SWAT Model.
AB  - Sediment delivery from hillslopes to rivers is spatially variable and may lead to
      long-term delays between initial erosion and related sediment yield at the
      watershed outlet. Consideration of spatial variability is important for
      developing sound strategies for water quality improvement and soil protection at
      the watershed scale. Hence, the Soil and Water Assessment Tool (SWAT) was
      modified and tested in this study to simulate the landscape transport capacity of
      sediment. The study area was the steeply sloped Arroio Lino watershed in southern
      Brazil. Observed sediment yield data at the watershed outlet were used to
      calibrate and validate a modified SWAT model. For the calibration period, the
      modified model performed better than the unaltered SWAT2009 version; the models
      achieved Nash-Sutcliffe efficiency (NSE) values of 0.7 and -0.1, respectively.
      Nash-Sutcliffe efficiencies were less for the validation period, but the modified
      model's NSE was higher than the unaltered model (-1.4 and -12.1, respectively).
      Despite the relatively low NSE values, the results of this first test are
      promising because the model modifications lowered the percent bias in sediment
      yield from 73 to 18%. Simulation results for the modified model indicated that
      approximately 60% of the mobilized soil is deposited along the landscape before
      it reaches the river channels. This research demonstrates the modified model's
      ability to simulate sediment yield in watersheds with steep slopes. The results
      suggest that integration of the sediment deposition routine in SWAT increases
      accuracy in steeper areas while significantly improving its ability to predict
      the spatial distribution of sediment deposition areas. Further work is needed
      regarding (i) improved strategies for spatially distributed sediment transport
      measurements (for improving process knowledge and model evaluation) and (ii)
      extensive model tests in other well instrumented experimental watersheds with
      differing topographic configurations and land uses. 

PMID- 25602541
TI  - Simulating land management options to reduce nitrate pollution in an agricultural
      watershed dominated by an alluvial aquifer.
AB  - The study area (Alegria watershed, Basque Country, Northern Spain) considered
      here is influenced by an important alluvial aquifer that plays a significant role
      in nitrate pollution from agricultural land use and management practices.
      Nitrates are transported primarily from the soil to the river through the
      alluvial aquifer. The agricultural activity covers 75% of the watershed and is
      located in a nitrate-vulnerable zone. The main objective of the study was to find
      land management options for water pollution abatement by using model systems. In
      a first step, the SWAT model was applied to simulate discharge and nitrate load
      in stream flow at the outlet of the catchment for the period between October 2009
      and June 2011. The LOADEST program was used to estimate the daily nitrate load
      from measured nitrate concentration. We achieved satisfactory simulation results
      for discharge and nitrate loads at monthly and daily time steps. The results
      revealed clear variations in the seasons: higher nitrate loads were achieved for
      winter (20,000 kg mo NO-N), and lower nitrate loads were simulated for the summer
      (<1000 kg mo NO-N) period. In a second step, the calibrated model was used to
      evaluate the long-term effects of best management practices (BMPs) for a 50-yr
      period by maintaining actual agricultural practices, reducing fertilizer
      application by 20%, splitting applications (same total N but applied over the
      growing period), and reducing 20% of the applied fertilizer amount and splitting
      the fertilizer doses. The BMPs were evaluated on the basis of local experience
      and farmer interaction. Results showed that reducing fertilizer amounts by 20%
      could lead to a reduction of 50% of the number of days exceeding the nitrate
      concentration limit value (50 mg L) set by the European Water Framework
      Directive. 

PMID- 25602542
TI  - Assessment of the Environmental Fate of the Herbicides Flufenacet and Metazachlor
      with the SWAT Model.
AB  - This study aims to assess the environmental fate of the commonly used herbicides
      flufenacet and metazachlor in the Northern German Lowlands with the
      ecohydrological Soil and Water Assessment Tool (SWAT model) and to test the
      sensitivity of pesticide-related input parameters on the modeled transport
      dynamics. The river discharge of the Kielstau watershed was calibrated (Nash
      Sutcliffe efficiency [NSE], 0.83; = 0.84) and validated (NSE, 0.76; = 0.77) for a
      daily time step. The environmental fate of metazachlor (NSE, 0.68; = 0.62) and
      flufenacet (NSE, 0.13; = 0.51) was simulated adequately. In comparison to
      metazachlor, the simulated flufenacet concentration and loads show a lower model
      efficiency due to the weaker simulation of the stream flow. The in-stream
      herbicide loads were less than 0.01% of the applied amount in the observed time
      period and thus not in conflict with European Environmental Legislation. The
      sensitivity analysis showed that, besides the accurate simulation of stream flow,
      the parameterization of the temporal and spatial distribution of the herbicide
      application throughout the watershed is the key factor for appropriate modeling
      results, whereas the physicochemical properties of the pesticides play a minor
      role in the modeling process. 

PMID- 25602543
TI  - Comparison and evaluation of model structures for the simulation of pollution
      fluxes in a tile-drained river basin.
AB  - The European Union Water Framework Directive requires an integrated pollution
      prevention plan at the river basin level. Hydrological river basin modeling tools
      are therefore promising tools to support the quantification of pollution
      originating from different sources. A limited number of studies have reported on
      the use of these models to predict pollution fluxes in tile-drained basins. This
      study focused on evaluating different modeling tools and modeling concepts to
      quantify the flow and nitrate fluxes in the Odense River basin using DAISY-MIKE
      SHE (DMS) and the Soil and Water Assessment Tool (SWAT). The results show that
      SWAT accurately predicted flow for daily and monthly time steps, whereas
      simulation of nitrate fluxes were more accurate at a monthly time step. In
      comparison to the DMS model, which takes into account the uncertainty of soil
      hydraulic and slurry parameters, SWAT results for flow and nitrate fit well
      within the range of DMS simulated values in high-flow periods but were slightly
      lower in low-flow periods. Despite the similarities of simulated flow and nitrate
      fluxes at the basin outlet, the two models predicted very different separations
      into flow components (overland flow, tile drainage, and groundwater flow) as well
      as nitrate fluxes from flow components. It was concluded that the assessment on
      which the model provides a better representation of the reality in terms of flow
      paths should not only be based on standard statistical metrics for the entire
      river basin but also needs to consider additional data, field experiments, and
      opinions of field experts. 

PMID- 25602545
TI  - Multiobjective calibration for comparing channel sediment routing models in the
      soil and water assessment tool.
AB  - Sediment transport is important for ecology and water quality in receiving
      waters. Physically based channel erosion methods were implemented in the Soil and
      Water Assessment Tool version 2009 (SWAT2009) to improve sediment concentration
      (SS) results. In the study, the default simplified Bagnold sediment routing
      method (EQN-0) and the physically based simplified Bagnold sediment routing
      method (EQN-1) were compared with Pareto fronts from multiobjective calibration.
      Two SWAT models using EQN-0 and EQN-1 were set up for a small agricultural Danish
      catchment and calibrated with multiobjective calibration on daily and weekly flow
      weighted SS (WF SS). Results showed that the Pareto front of EQN-1 was slightly
      closer to the optimal point than EQN-0 in the objective space. Trade-off between
      WF SS and daily flow in EQN-1 was smaller than in EQN-0. The EQN-0 method
      generated more surface erosion to improve WF SS. The EQN-1 method generated more
      base flow to improve WF SS. The EQN-1 method was less dependent on surface
      erosion and simulated peak and low values of WF SS better than EQN-0. Therefore,
      EQN-1 is more suitable than EQN-0 in modeling SS in small lowland catchments. 

PMID- 25602544
TI  - Effects of urbanization and climate change on stream health in north-central
      Texas.
AB  - Estimation of stream health involves the analysis of changes in aquatic species,
      riparian vegetation, microinvertebrates, and channel degradation due to
      hydrologic changes occurring from anthropogenic activities. In this study, we
      quantified stream health changes arising from urbanization and climate change
      using a combination of the widely accepted Indicators of Hydrologic Alteration
      (IHA) and Dundee Hydrologic Regime Assessment Method (DHRAM) on a rapidly
      urbanized watershed in the Dallas-Fort Worth metropolitan area in Texas.
      Historical flow data were split into pre-alteration and post-alteration periods.
      The influence of climate change on stream health was analyzed by dividing the
      precipitation data into three groups of dry, average, and wet conditions based on
      recorded annual precipitation. Hydrologic indicators were evaluated for all three
      of the climate scenarios to estimate the stream health changes brought about by
      climate change. The effect of urbanization on stream health was analyzed for a
      specific subwatershed where urbanization occurred dramatically but no stream flow
      data were available using the widely used watershed-scale Soil and Water
      Assessment Tool (SWAT) model. The results of this study identify negative impacts
      to stream health with increasing urbanization and indicate that dry weather has
      more impact on stream health than wet weather. The IHA-DHRAM approach and SWAT
      model prove to be useful tools to estimate stream health at the watershed scale. 

PMID- 25602546
TI  - Hydrologic modeling in a small mediterranean basin as a tool to assess the
      feasibility of a limno-reservoir.
AB  - The SWAT model was applied to the Ompolveda River Basin (Guadalajara, central
      Spain) to assess the hydrological feasibility of the Pareja Limno-reservoir. A
      limno-reservoir is a water management infrastructure designed to counteract some
      negative impacts caused by large reservoirs under Mediterranean climate. Highly
      detailed inputs were selected to set up the model. Its performance was evaluated
      by graphical and statistical techniques and compared with the previous knowledge
      of the basin. An overall good performance was obtained during the calibration and
      validation periods (monthly and annual NSE values of 0.67 and 0.60, respectively,
      for calibration and 0.70 and 0.83, respectively, for validation). Total discharge
      was well simulated, and flow components prediction was acceptable. However, the
      model is not accurate at predicting evapotranspiration. Once evaluated, the model
      was used to simulate the water discharge into the Pareja Limno-reservoir during
      2008 and 2009, establishing a water balance and assessing its hydrologic
      feasibility. The water balance predicted the absence of surplus during summer
      (2008 and 2009) and autumn (2009), matching up with the decrease of water level
      and demonstrating the usefulness of SWAT as a tool to evaluate the hydrologic
      feasibility of the Pareja Limno-reservoir. Very low discharges from the Ompolveda
      River after a sequence of normal and dry years are the main factors responsible
      of this phenomenon, whereas the effect of the wastewater flow redirection in the
      Pareja village is negligible. These results question the usefulness of the Pareja
      Limno-reservoir during summer, the most favorable season for recreational
      activities. 

PMID- 25602547
TI  - Soil and water assessment tool model calibration results for different catchment
      sizes in poland.
AB  - The watershed model SWAT (Soil and Water Assessment Tool) can be used to
      implement the requirements of international agreements that Poland has ratified.
      Among these requirements are the establishment of catchment-based, rather than
      administrative-based, management plans and spatial information systems.
      Furthermore, Polish law requires that management of water resources be based on
      catchment systems. This article explores the use of the SWAT model in the
      implementation of catchment-based water management in Poland. Specifically, the
      impacts of basin size on calibration and on the results of the simulation process
      were analyzed. SWAT was set up and calibrated for three Polish watersheds of
      varying sizes: (i) Gasawka, a small basin (>593.7 km), (ii) Rega, a medium-sized
      basin (2766.8 km), and (iii) Warta, a large basin (54,500 km) representing about
      17.4% of Polish territory. The results indicated that the size of the catchment
      has an impact on the calibration process and simulation outputs. Several factors
      influenced by the size of the catchment affected the modeling results. Among
      these factors are the number of measurement points within the basin and the
      length of the measuring period and data quality at checkpoints as determined by
      the position of the measuring station. It was concluded that the SWAT model is a
      suitable tool for the implementation of catchment-based water management in
      Poland regardless of watershed size. 

PMID- 25602548
TI  - Large-scale hydrological simulations using the soil water assessment tool,
      protocol development, and application in the danube basin.
AB  - The Water Framework Directive of the European Union requires member states to
      achieve good ecological status of all water bodies. A harmonized pan-European
      assessment of water resources availability and quality, as affected by various
      management options, is necessary for a successful implementation of European
      environmental legislation. In this context, we developed a methodology to predict
      surface water flow at the pan-European scale using available datasets. Among the
      hydrological models available, the Soil Water Assessment Tool was selected
      because its characteristics make it suitable for large-scale applications with
      limited data requirements. This paper presents the results for the Danube pilot
      basin. The Danube Basin is one of the largest European watersheds, covering
      approximately 803,000 km and portions of 14 countries. The modeling data used
      included land use and management information, a detailed soil parameters map, and
      high-resolution climate data. The Danube Basin was divided into 4663
      subwatersheds of an average size of 179 km. A modeling protocol is proposed to
      cope with the problems of hydrological regionalization from gauged to ungauged
      watersheds and overparameterization and identifiability, which are usually
      present during calibration. The protocol involves a cluster analysis for the
      determination of hydrological regions and multiobjective calibration using a
      combination of manual and automated calibration. The proposed protocol was
      successfully implemented, with the modeled discharges capturing well the overall
      hydrological behavior of the basin. 

PMID- 25602549
TI  - Effect of climate change on environmental flow indicators in the narew basin,
      poland.
AB  - Environmental flows-the quantity of water required to maintain a river ecosystem
      in its desired state-are of particular importance in areas of high natural value.
      Water-dependent ecosystems are exposed to the risk of climate change through
      altered precipitation and evaporation. Rivers in the Narew basin in northeastern
      Poland are known for their valuable river and wetland ecosystems, many of them in
      pristine or near-pristine condition. The objective of this study was to assess
      changes in the environmental flow regime of the Narew river system, caused by
      climate change, as simulated by hydrological models with different degrees of
      physical characterization and spatial aggregation. Two models were assessed: the
      river basin scale model Soil and Water Assessment Tool (SWAT) and the continental
      model of water availability and use WaterGAP. Future climate change scenarios
      were provided by two general circulation models coupled with the A2 emission
      scenario: IPSL-CM4 and MIROC3.2. To assess the impact of climate change on
      environmental flows, a method based conceptually on the "range of variability"
      approach was used. The results indicate that the environmental flow regime in the
      Narew basin is subject to climate change risk, whose magnitude and spatial
      variability varies with climate model and hydrological modeling scale. Most of
      the analyzed sites experienced moderate impacts for the Generic Environmental
      Flow Indicator (GEFI), the Floodplain Inundation Indicator, and the River Habitat
      Availability Indicator. The consistency between SWAT and WaterGAP for GEFI was
      medium: in 55 to 66% of analyzed sites, the models suggested the same level of
      impact. Hence, we suggest that state-of-the-art, high-resolution, global- or
      continental-scale models, such as WaterGAP, could be useful tools for water
      management decision-makers and wetland conservation practitioners, whereas models
      such as SWAT should serve as a complementary tool for more specific, smaller
      scale, local assessments. 

PMID- 25602550
TI  - Using the soil and water assessment tool to estimate dissolved inorganic nitrogen
      water pollution abatement cost functions in central portugal.
AB  - Coastal aquatic ecosystems are increasingly affected by diffuse source nutrient
      water pollution from agricultural activities in coastal catchments, even though
      these ecosystems are important from a social, environmental and economic
      perspective. To warrant sustainable economic development of coastal regions, we
      need to balance marginal costs from coastal catchment water pollution abatement
      and associated marginal benefits from coastal resource appreciation. Diffuse
      source water pollution abatement costs across agricultural sectors are not easily
      determined given the spatial heterogeneity in biophysical and agro-ecological
      conditions as well as the available range of best agricultural practices (BAPs)
      for water quality improvement. We demonstrate how the Soil and Water Assessment
      Tool (SWAT) can be used to estimate diffuse-source water pollution abatement cost
      functions across agricultural land use categories based on a stepwise adoption of
      identified BAPs for water quality improvement and corresponding SWAT-based
      estimates for agricultural production, agricultural incomes, and water pollution
      deliveries. Results for the case of dissolved inorganic nitrogen (DIN) surface
      water pollution by the key agricultural land use categories ("annual crops,"
      "vineyards," and "mixed annual crops & vineyards") in the Vouga catchment in
      central Portugal show that no win-win agricultural practices are available within
      the assessed BAPs for DIN water quality improvement. Estimated abatement costs
      increase quadratically in the rate of water pollution abatement, with largest
      abatement costs for the "mixed annual crops & vineyards" land use category
      (between 41,900 and 51,900 ? tDIN yr) and fairly similar abatement costs across
      the "vineyards" and "annual crops" land use categories (between 7300 and 15,200 ?
      tDIN yr). 

PMID- 25602551
TI  - An integrated modeling approach for estimating the water quality benefits of
      conservation practices at the river basin scale.
AB  - The USDA initiated the Conservation Effects Assessment Project (CEAP) to quantify
      the environmental benefits of conservation practices at regional and national
      scales. For this assessment, a sampling and modeling approach is used. This paper
      provides a technical overview of the modeling approach used in CEAP cropland
      assessment to estimate the off-site water quality benefits of conservation
      practices using the Ohio River Basin (ORB) as an example. The modeling approach
      uses a farm-scale model, Agricultural Policy Environmental Extender (APEX), and a
      watershed scale model (the Soil and Water Assessment Tool [SWAT]) and databases
      in the Hydrologic Unit Modeling for the United States system. Databases of land
      use, soils, land use management, topography, weather, point sources, and
      atmospheric depositions were developed to derive model inputs. APEX simulates the
      cultivated cropland, Conserve Reserve Program land, and the practices implemented
      on them, whereas SWAT simulates the noncultivated land (e.g., pasture, range,
      urban, and forest) and point sources. Simulation results from APEX are input into
      SWAT. SWAT routes all sources, including APEX's, to the basin outlet through each
      eight-digit watershed. Each basin is calibrated for stream flow, sediment, and
      nutrient loads at multiple gaging sites and turned in for simulating the effects
      of conservation practice scenarios on water quality. Results indicate that
      sediment, nitrogen, and phosphorus loads delivered to the Mississippi River from
      ORB could be reduced by 16, 15, and 23%, respectively, due to current
      conservation practices. Modeling tools are useful to provide science-based
      information for assessing existing conservation programs, developing future
      programs, and developing insights on load reductions necessary for hypoxia in the
      Gulf of Mexico. 

PMID- 25602552
TI  - Comparison of Temperature-Index Snowmelt Models for Use within an Operational
      Water Quality Model.
AB  - The accurate prediction of snowmelt runoff is a critical component of integrated
      hydrological and water quality models in regions where snowfall constitutes a
      significant portion of the annual precipitation. In cold regions, the
      accumulation of a snowpack and the subsequent spring snowmelt generally
      constitutes a major proportion of the annual water yield. Furthermore, the
      snowmelt runoff transports significant quantities of sediment and nutrients to
      receiving streams and strongly influences downstream water quality. Temperature
      index models are commonly used in operational hydrological and water quality
      models to predict snowmelt runoff. Due to their simplicity, computational
      efficiency, low data requirements, and ability to consistently achieve good
      results, numerous temperature-index models of varying complexity have been
      developed in the past few decades. The objective of this study was to determine
      how temperature-index models of varying complexity would affect the performance
      of the water quality model SWAT (a modified version of SWAT that was developed
      for watersheds dominated by boreal forest) for predicting runoff. Temperature
      index models used by several operational hydrological models were incorporated
      into SWAT. Model performance was tested on five watersheds on the Canadian Boreal
      Plain whose hydrologic response is dominated by snowmelt runoff. The results of
      this study indicate that simpler temperature-index models can perform as well as
      more complex temperature-index models for predicting runoff from the study
      watersheds. The outcome of this study has important implications because the
      incorporation of simpler temperature-index snowmelt models into hydrological and
      water quality models can lead to a reduction in the number of parameters that
      need to be optimized without sacrificing predictive accuracy. 

PMID- 25602553
TI  - SWAT Check: A Screening Tool to Assist Users in the Identification of Potential
      Model Application Problems.
AB  - The Soil and Water Assessment Tool (SWAT) is a basin-scale hydrologic model
      developed by the United States Department of Agriculture Agricultural Research
      Service. SWAT's broad applicability, user-friendly model interfaces, and
      automatic calibration software have led to a rapid increase in the number of new
      users. These advancements also allow less experienced users to conduct SWAT
      modeling applications. In particular, the use of automated calibration software
      may produce simulated values that appear appropriate because they adequately
      mimic measured data used in calibration and validation. Autocalibrated model
      applications (and often those of unexperienced modelers) may contain input data
      errors and inappropriate parameter adjustments not readily identified by users or
      the autocalibration software. The objective of this research was to develop a
      program to assist users in the identification of potential model application
      problems. The resulting "SWAT Check" is a stand-alone Microsoft Windows program
      that (i) reads selected SWAT output and alerts users of values outside the
      typical range; (ii) creates process-based figures for visualization of the
      appropriateness of output values, including important outputs that are commonly
      ignored; and (iii) detects and alerts users of common model application errors.
      By alerting users to potential model application problems, this software should
      assist the SWAT community in developing more reliable modeling applications. 

PMID- 25602554
TI  - Development and testing of an in-stream phosphorus cycling model for the soil and
      water assessment tool.
AB  - The Soil and Water Assessment Tool is widely used to predict the fate and
      transport of phosphorus (P) from the landscape through streams and rivers. The
      current in-stream P submodel may not be suitable for many stream systems,
      particularly those dominated by attached algae and those affected by point
      sources. In this research, we developed an alternative submodel based on the
      equilibrium P concentration concept coupled with a particulate scour and
      deposition model. This submodel was integrated with the SWAT model and applied to
      the Illinois River Watershed in Oklahoma, a basin influenced by waste water
      treatment plant discharges and extensive poultry litter application. The model
      was calibrated and validated using measured data. Highly variable in-stream P
      concentrations and equilibrium P concentration values were predicted spatially
      and temporally. The model also predicted the gradual storage of P in streambed
      sediments and the resuspension of this P during periodic high-flow flushing
      events. Waste water treatment plants were predicted to have a profound effect on
      P dynamics in the Illinois River due to their constant discharge even under base
      flow conditions. A better understanding of P dynamics in stream systems using the
      revised submodel may lead to the development of more effective mitigation
      strategies to control the impact of P from point and nonpoint sources. 

PMID- 25602555
TI  - Validation of a quantitative phosphorus loss assessment tool.
AB  - Pasture Phosphorus Management Plus (PPM Plus) is a tool that allows nutrient
      management and conservation planners to evaluate phosphorus (P) loss from
      agricultural fields. This tool uses a modified version of the widely used Soil
      and Water Assessment Tool model with a vastly simplified interface. The
      development of PPM Plus has been fully described in previous publications; in
      this article we evaluate the accuracy of PPM Plus using 286 field-years of
      runoff, sediment, and P validation data from runoff studies at various locations
      in Oklahoma, Texas, Arkansas, and Georgia. Land uses include pasture, small
      grains, and row crops with rainfall ranging from 630 to 1390 mm yr, with and
      without animal manure application. PPM Plus explained 68% of the variability in
      total P loss, 56% of runoff, and 73% of the variability of sediment yield. An
      empirical model developed from these data using soil test P, total applied P,
      slope, and precipitation only accounted for 15% of the variability in total P
      loss, which implies that a process-based model is required to account for the
      diversity present in these data. PPM Plus is an easy-to-use conservation planning
      tool for P loss prediction, which, with modification, could be applicable at the
      regional and national scales. 

PMID- 25602556
TI  - Simulation climate change impact on runoff and sediment yield in a small
      watershed in the basque country, northern Spain.
AB  - Climate change is likely to have an impact on runoff and fluvial sediments in
      watersheds. These factors are among those used to characterize water bodies in
      relation to the European Water Framework Directive (WFD). Hence, it is important
      to investigate the extent to which climate change may hinder the achievement of
      the objectives of the WFD. We explored the potential impact of climate change on
      runoff and sediment yield for the Aixola watershed using the Soil and Water
      Assessment Tool (SWAT). The model calibration (2007-2010) and validation (2005
      2006) results were rated as satisfactory. Subsequently, simulations were run for
      four climate change model-scenario combinations based on two general circulation
      models (CGCM2 and ECHAM4) under two emissions scenarios (A2 and B2) from 2011 to
      2100. All combinations predicted that runoff and sediment yield would decrease
      compared with baseline (1961-1990). Three combinations suggested that runoff and
      sediments would decrease by 0.13 to 0.45 m s and 0.11 to 0.43 t every year from
      2011 to 2100. However, the CGCM2-B2 scenario resulted in an "extremely likely"
      increase in runoff and sediments of 0.94 m s and 0.57 t every year. These
      variations in annual sediment yield are closely related to changes in
      precipitation. The high degree of uncertainty in the results must be considered
      when assessing potential impacts and making decisions about adaptation measures.
      Nevertheless, this first attempt to estimate future sediment yields in our region
      could be a useful starting point to explore future hydrological impacts in the
      area. 

PMID- 25602557
TI  - Sustainable Uses of FGD Gypsum in Agricultural Systems: Introduction.
AB  - Interest in using gypsum as a management tool to improve crop yields and soil and
      water quality has recently increased. Abundant supply and availability of flue
      gas desulfurization (FGD) gypsum, a by-product of scrubbing sulfur from
      combustion gases at coal-fired power plants, in major agricultural producing
      regions within the last two decades has attributed to this interest. Currently,
      published data on the long-term sustainability of FGD gypsum use in agricultural
      systems is limited. This has led to organization of the American Society of
      Agronomy's Community "By-product Gypsum Uses in Agriculture" and a special
      collection of nine technical research articles on various issues related to FGD
      gypsum uses in agricultural systems. A brief review of FGD gypsum, rationale for
      the special collection, overviews of articles, knowledge gaps, and future
      research directions are presented in this introductory paper. The nine articles
      are focused in three general areas: (i) mercury and other trace element impacts,
      (ii) water quality impacts, and (iii) agronomic responses and soil physical
      changes. While this is not an exhaustive review of the topic, results indicate
      that FGD gypsum use in sustainable agricultural production systems is promising.
      The environmental impacts of FGD gypsum are mostly positive, with only a few
      negative results observed, even when applied at rates representing cumulative 80
      year applications. Thus, FGD gypsum, if properly managed, seems to represent an
      important potential input into agricultural systems. 

PMID- 25602558
TI  - Investigation of the potential for mercury release from flue gas desulfurization
      solids applied as an agricultural amendment.
AB  - The potential for beneficial use of flue gas desulfurization-derived gypsum
      (FGDG), a coal combustion byproduct, as an agricultural soil amendment is
      currently being debated. This study investigated the hypothesis that Hg released
      to air from FGDG will be reduced when amended to planted and bare soils. The
      potential for enhanced methylmercury (MeHg) production and Hg uptake by plants in
      soils amended with FGDG was also investigated. Flue gas desulfurization-derived
      gypsum from three sources was homogenized into three soils at 4.5, 45, and 170 t
      ha and applied at 4.9 t ha as a thin layer to simulate tilled and no-till
      applications, respectively. Twenty-four-hour Hg flux was measured from unamended
      and FGDG-amended soils on a seasonal time step over 1 yr and after disturbing,
      watering, and planting. Methylmercury in soil, irrigation drainage, and total Hg
      in plant tissues were quantified. Results should be interpreted within the
      confines of the experimental setting and materials used for this study. Total Hg
      concentrations in soils, homogenized with FGDG, were below that considered
      representative of soil with background values (<100 ng g). Emissions from amended
      soils were higher initially relative to unamended soils but became similar over
      time. Significantly less Hg (2%) was lost to the air from FGDG-amended soils (90
      g FGDG added for lowest application) than that released from the FGDG alone (30
      70%) (50 g FGDG) over 1 yr. Total Hg and MeHg in irrigation drainage and total Hg
      concentrations measured in plants were similar for amended and unamended soils. 

PMID- 25602559
TI  - Effects of gypsum on trace metals in soils and earthworms.
AB  - Mined gypsum has been beneficially used for many years as an agricultural
      amendment. A large amount of flue gas desulfurization (FGD) gypsum is produced by
      removal of SO from flue gas streams when fuels with high S content are burned.
      The FGD gypsum, similar to mined gypsum, can enhance crop production. However,
      information is lacking concerning the potential environmental impacts of trace
      metals, especially Hg, in the FGD gypsum. Flue gas desulfurization and mined
      gypsums were evaluated to determine their ability to affect concentrations of Hg
      and other trace elements in soils and earthworms. The study was conducted at four
      field sites across the United States (Ohio, Indiana, Alabama, and Wisconsin). The
      application rates of gypsums ranged from 2.2 Mg ha in Indiana to 20 Mg ha in Ohio
      and Alabama. These rates are 2 to 10 times higher than typically recommended. The
      lengths of time from gypsum application to soil and earthworm sampling were 5 and
      18 mo in Ohio, 6 mo in Indiana, 11 mo in Alabama, and 4 mo in Wisconsin.
      Earthworm numbers and biomass were decreased by FGD and mined gypsums in Ohio.
      Among all the elements examined, Hg was slightly increased in soils and
      earthworms in the FGD gypsum treatments compared with the control and the mined
      gypsum treatments. The differences were not statistically significant except for
      the Hg concentration in the soil at the Wisconsin site. Selenium in earthworms in
      the FGD gypsum treatments was statistically higher than in the controls but not
      higher than in the mined gypsum treatments at the Indiana and Wisconsin sites.
      Bioaccumulation factors for nondepurated earthworms were statistically similar or
      lower for the FGD gypsum treatments compared with the controls for all elements.
      Use of FGD gypsum at normal recommended agricultural rates seems not to have a
      significant impact on concentrations of trace metals in earthworms and soils. 

PMID- 25602560
TI  - Impact of flue gas desulfurization gypsum application on water quality in a
      coastal plain soil.
AB  - There are growing concerns regarding the fate of nutrients, especially phosphorus
      (P), from land application of animal waste. One approach being studied to reduce
      runoff losses of P is to treat manure or the soil receiving manure with chemical
      amendments such as gypsum. This study used rainfall simulations to examine the
      impact of flue gas desulfurization (FGD) gypsum application on runoff nutrient
      losses on a Coastal Plains soil (Luverne sandy loam; fine, mixed, semiactive,
      thermic Typic Hapludults). Four rates of FGD gypsum (0, 2.2, 4.4, and 8.9 Mg ha)
      were applied to plots of Coastal Bermudagrass ( L.) that had received application
      of 13.4 Mg ha poultry litter. Plots with 8.9 Mg ha FGD gypsum but no poultry
      litter and plots with neither poultry litter nor FGD gypsum were also used.
      Rainfall simulation was used to generate water runoff for 60 min, and samples
      were analyzed for soluble reactive P (SRP) and soluble Al, B, Ca, Cu, Fe, K, Mg,
      Mn, Na, and Zn. Total concentration of Ca, Mg, K, Na, Fe, Mn, and Zn and
      concentration of heavy metals Ar, Hg, Al, Sb, Ba, Be, Cd, Cr, Co, Cu, Pb, Ni, Si,
      V, Se, Tl, and hexavalent chromium were also analyzed. Results indicated a
      maximum of 61% reduction in SRP concentration in runoff with the application of
      8.9 Mg ha FGD gypsum. This translated to a 51% reduction in total SRP load during
      the 60-min runoff event. Concentrations of heavy metals in runoff were all found
      to be below detection limits. The results indicated that use of 4.4 Mg ha FGD
      gypsum on Coastal Plains pastures receiving poultry litter could be an effective
      method of reducing SRP losses to the environment. 

PMID- 25602561
TI  - Flue gas desulfurization gypsum: implication for runoff and nutrient losses
      associated with broiler litter use on pastures on ultisols.
AB  - Gypsum has been shown to reduce runoff on soils prone to crust formation in the
      southeastern United States. Increased infiltration from gypsum applications could
      therefore help reduce runoff P and other nutrient losses from application of
      broiler litter (BL), a nutrient-rich fertilizer. In rainfall simulation
      experiments in June 2009 and May 2011, runoff and nutrient (N, P, Ca, Mg) losses
      in runoff were compared among treatments consisting of 0, 2.2, 4.5, and 9.0 Mg ha
      flue gas desulfurization gypsum (FGDG) combined with 13.5 Mg ha of BL and two
      control treatments of (0-0) and (9.0-0.0) Mg ha (FGDG-BL). A randomized block
      design with three replications was set up on a Cecil (Typic Kanhapludult) soil
      growing Coastal bermudagrass ( L.) for hay near Watkinsville, Georgia. Amendments
      were applied each April from 2009 to 2011. A reduction in runoff of 30% each year
      from the (9.0-13.5) compared with the (0-0) treatment was not statistically
      significant. Gypsum was effective in reducing concentration and load in one of
      the two study years: P and NH-N in 2009 (up to 83%) and NO-N in 2011 (up to 73%).
      A combination of factors related to weather extremes, timing of FGDG and BL
      applications, and their implication on soil and vegetation responses at different
      landscape positions might have caused the different responses between years.
      Additional studies focused on isolating the impacts of such factors would be
      helpful to ascertain the effectiveness of multiyear applications of FGDG as a
      best management practice to reduce P and other nutrient losses in soils of the
      southeastern United States. 

PMID- 25602562
TI  - Effects of bedding materials in applied poultry litter and immobilizing agents on
      runoff water, soil properties, and bermudagrass growth.
AB  - Poultry producers in the United States have begun using different types of
      bedding materials in production houses. Release into the environment of nutrients
      from applied poultry litter (PL) made with different bedding materials has not
      been investigated, and little information is available on nutrient concentrations
      in soils that receive broiler litter made with such materials. In this greenhouse
      study, two bedding materials (rice hulls and pine chips) in PL and two nutrient
      immobilizing agents (gypsum and biochar) were applied to bermudagrass, and
      chemical and microbial contents of runoff water, soil properties, and plant
      growth were evaluated. Treatments with rice hull bedding material in PL had less
      runoff nutrient and greater soil soluble N and P compared with pine chip bedding.
      Gypsum and biochar both significantly reduced C, N, P, Cu, and Zn losses from the
      first runoff event, which were reduced by 26, 30, 37, 38, and 38% and by 25, 24,
      30, 29, and 35%, respectively, but only gypsum obviously reduced these nutrients
      from later events. Potassium, Ca, Mg, and Mn increased by 2, 36, 11, and 9 times,
      respectively, and soluble P, Cu, and Fe significantly decreased by 68, 72, and
      98%, respectively, in soil amended with gypsum. Rice hull PL in combination with
      gypsum significantly increased the growth of bermudagrass. Our results indicate
      that rice hull PL posed less risk for nutrient loss than pine chip PL when
      applied to fields and that gypsum was better than biochar for reducing runoff C,
      N, P, and Cu. 

PMID- 25602563
TI  - Hydrologic transport of fecal bacteria attenuated by flue gas desulfurization
      gypsum.
AB  - Flue gas desulfurization (FGD) gypsum is a byproduct of coal-fired power plants.
      Its application to agricultural fields may increase water infiltration, reduce
      soil erosion, and decrease nutrient losses from applications of animal manures.
      It may also reduce fecal bacterial contamination of surface waters. We tested the
      hypothesis that FGD gypsum applications would decrease the load of and the fecal
      indicator bacterium from poultry litter applications. Two rainfall simulation
      experiments were undertaken: one in spring 2009 and one in spring 2011. Six
      treatments consisted of four rates of FGD gypsum (0, 2.2, 4.5, and 9.0 Mg ha)
      with poultry litter (13.5 Mg ha and two controls) in a randomized, complete-block
      design with three replications. Each replicate 4- * 6-m plot contained a single 1
      * 2-m subplot that was delineated by metal plates and a flume that captured
      total overland flow or runoff. Rainfall was applied at ~64 mm h. Volume of
      overland runoff was measured and subsampled for analysis every 10 min for 1 h.
      Flow-weighted concentrations, total loads, and soil concentrations of were
      determined. was not detected in runoff. No significant differences between
      treatments were observed for the 2009 rainfall simulation. However, after 3 yr of
      FGD gypsum applications, the highest rate of FGD gypsum resulted in decreased
      flow-weighted concentrations and total loads of . Flue gas desulfurization gypsum
      applications may be a management practice that reduces microbial contamination of
      surface waters from manure applied to agricultural fields in the southeastern
      United States. 

PMID- 25602564
TI  - Application of flue gas desulfurization gypsum and its impact on wheat grain and
      soil chemistry.
AB  - The 11 major electricity-generating coal combustion stations in the northern
      Great Plains have the potential to produce almost 1 million Mg of flue gas
      desulfurization gypsum (FGDG) annually, which is a very attractive fertilizer (Ca
      and S) and amendment for sodic and acid soils. The potential environmental
      impacts of applying FGDG to soils in this region have not been fully
      investigated. The objectives of this research were to determine the influence of
      FGDG on soil chemical characteristics and to determine the impact that FGDG has
      on hard red spring wheat ( L.) yields and element analysis of the grain. Flue gas
      desulfurization gypsum and commercial gypsum were applied at rates of 0, 2.24,
      11.2, and 22.4 Mg ha to two soils in southwestern North Dakota in the spring of
      2007. Soil and grain chemistries were monitored for two growing seasons. Wheat
      grain yields and elemental analysis of the grain were generally not affected by
      the gypsum treatments, indicating that the gypsum products did not negatively
      affect plant productivity. In addition, soil elemental analysis was similar
      across the treatments at both sites in both years. The results from this study
      indicate that its application to soil at rates used for sodic soil remediation
      (Mg ha) did not negatively affect the chemistries of either the soils or the
      wheat evaluated in this study compared with a commercial gypsum product or
      control soils. 

PMID- 25602565
TI  - Effects of flue gas desulfurization and mined gypsums on soil properties and on
      hay and corn growth in eastern ohio.
AB  - Gypsum (CaSO.2HO) is a quality source of Ca and S and has various beneficial uses
      that can improve agricultural production. This study was conducted to compare
      rates of flue gas desulfurization (FGD) gypsum and commercially available
      agricultural (i.e., mined) gypsum as soil amendments on soils typical of eastern
      Ohio or western Pennsylvania. Two field experiments were conducted, one involving
      a mixed grass hay field and the other corn ( L.). Gypsum was applied once at
      rates of 0.2, 2.0, and 20 Mg ha and a seventh treatment was a zero rate control.
      Corn grain yields response to gypsum was mixed with significant differences
      between low and high gypsum rates in 2010 but not between gypsum and no gypsum
      treatments. In the hay study, the low and intermediate gypsum rates generally did
      not result in any significant changes compared with the control treatment. At the
      high rate of 20 Mg ha, the following results were observed for the hay study: (i)
      both gypsums generally increased Ca, S, and soluble salts (electrical
      conductivity) in the topsoil and subsoil, when compared with the control; (ii)
      the FGD gypsum decreased Mg in soil when compared with all other treatments, and
      mined gypsum decreased Mg when compared with the control; and (iii) there were
      few effects on soil concentrations of trace elements, including Hg. Also at the
      high application rate, hay yield for the first cutting (May) in 2009 and 2010 was
      significantly less for mined and FGD gypsum compared with the control, but
      increased yields in subsequent cutting resulted in no significant treatment
      differences in total annual hay yield for 2008, 2009, or 2010 or cumulative yield
      for 2008 to 2010. Overall, for the hay study, the absence of significant soil
      chemical effects for the intermediate gypsum rate and the decrease in soil Mg
      concentrations for the high gypsum rate indicate that an application rate of
      approximately 2.0 Mg ha would be optimal for this soil. 

PMID- 25602566
TI  - In-season effect of flue gas desulfurization gypsum on soil physical properties.
AB  - There is renewed interest in the application of gypsum to agricultural lands,
      particularly of gypsum produced during flue gas desulfurization (FGD) at coal
      burning power plants. We studied the effects of land application of FGD gypsum to
      corn ( L.) in watersheds draining to the Great Lakes. The FGD gypsum was surface
      applied at 11 sites at rates of 0, 1120, 2240, and 4480 kg ha after planting to 3
      m by 7.6-m field plots. Approximately 12 wk after application, penetration
      resistance and hydraulic conductivity were measured in situ, and samples were
      collected for determination of bulk density and aggregate stability. No treatment
      effect was detected for penetration resistance or hydraulic conductivity. A
      positive treatment effect was seen for bulk density at only 2 of 10 sites tested.
      Aggregate stability reacted similarly across all sites and was decreased with the
      highest application of FGD gypsum, whereas the lower rates were not different
      from the control. Overall, there were few beneficial effects of the FGD gypsum to
      soil physical properties in the year of application. 

PMID- 25602568
TI  - Nitrous oxide emission from cropland and adjacent riparian buffers in contrasting
      hydrogeomorphic settings.
AB  - Riparian buffers are important nitrate (NO) sinks in agricultural watersheds, but
      limited information is available regarding the intensity and control of nitrous
      oxide (NO) emission from these buffers. This study monitored (December 2009-May
      2011) NO fluxes at two agricultural riparian buffers in the White River watershed
      in Indiana to assess the impact of land use and hydrogeomorphologic (HGM)
      attributes on emission. The study sites included a riparian forest in a glacial
      outwash/alluvium setting (White River [WR]) and a grassed riparian buffer in tile
      drained till plains (Leary Weber Ditch [LWD]). Adjacent corn ( L.) fields were
      monitored for land use assessment. Analysis of variance identified season, land
      use (riparian buffer vs. crop field), and site geomorphology as major drivers of
      NO fluxes. Strong relationships between N mineralization and NO fluxes were found
      at both sites, but relationships with other nutrient cycling indicators (C/N
      ratio, dissolved organic C, microbial biomass C) were detected only at LWD.
      Nitrous oxide emission showed strong seasonal variability; the largest NO peaks
      occurred in late spring/early summer as a result of flooding at the WR riparian
      buffer (up to 27.8 mg NO-N m d) and N fertilizer application to crop fields.
      Annual NO emission (kg NO-N ha) was higher in the crop fields (WR: 7.82; LWD:
      6.37) than in the riparian areas. A significant difference ( < 0.02) in annual NO
      emission between the riparian buffers was detected (4.32 vs. 1.03 kg NO-N ha at
      WR and LWD, respectively), and this difference was attributed to site
      geomorphology and flooding (WR is flood prone; no flooding occurred at tile
      drained LWD). The study results demonstrate the significance of landscape
      geomorphology and land-stream connection (i.e., flood potential) as drivers of NO
      emission in riparian buffers and therefore argue that an HGM-based approach
      should be especially suitable for determination of regional NO budget in riparian
      ecosystems. 

PMID- 25602567
TI  - Study of Cloud Water Samples Collected over Northern Poland.
AB  - The paper gives the results of the first studies on the chemistry of cloud water
      collected during 3 mo (Aug.-Oct. 2010) in the free atmosphere over the area to
      the south of the Tri-City (Gdansk-Sopot-Gdynia) conurbation on the Gulf of
      Gdansk, Poland. Taken from cumulus, stratus, and stratocumulus clouds by means of
      an aircraft-mounted collector, the water samples were analyzed for the following
      contaminants: anions (chlorides, fluorides, nitrates, sulfates, and phosphates),
      cations (lithium, sodium, potassium, ammonium, calcium, and magnesium), and trace
      metals. In addition, pH values were measured, and the type and composition of
      suspended particulate matter was determined. We discuss the relationship between
      the concentration of inorganic ions and the type of cloud from which water was
      sampled. The chemistry is also likely related to the circulation pattern and
      inflow of clean air masses from the Baltic Sea. Moreover, a relationship was
      found between the composition of the samples examined and the location of
      pollutant emission sources. 

PMID- 25602569
TI  - Biodegradation of Polychlorinated Dibenzo--Dioxins by Strain NSYSU.
AB  - The dioxin-degrading bacterium strain NSYSU (NSYSU strain) has been isolated from
      dioxin-contaminated soil by selective enrichment techniques. In the present
      study, the NSYSU strain was investigated for its capability to biodegrade
      polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) under aerobic and anaerobic conditions. High-resolution gas
      chromatography-mass spectrometry and a chemically activated luciferase gene
      expression bioassay were performed to determine the presence of dioxin compounds.
      The results indicate that the NSYSU strain could degrade PCDDs and PCDFs under
      anaerobic conditions in liquid cultures. The main intermediates of the
      dechlorination process were identified. The results of the bioreactor test
      indicate that the NSYSU strain could also degrade PCDDs and PCDFs effectively in
      soil slurries under aerobic conditions. Results from the bioreactor experiment
      show that approximately 98 and 97% of octachlorodibenzofuran and OCDD were
      degraded, respectively. The dioxin concentrations in soil slurry decreased from
      5823 to 1198 pg toxic equivalency g, resulting in total dioxin removal of 79%.
      These first findings suggest that the NSYSU strain has the potential to be an
      effective tool for the bioremediation of soils contaminated with highly
      recalcitrant organic compounds. 

PMID- 25602570
TI  - Application of multivariate statistical methodology to model factors influencing
      fate and transport of fecal pollution in surface waters.
AB  - The increasing number of polluted watersheds and water bodies with total maximum
      daily loads (TMDLs) has resulted in increased research to find methods that
      effectively and universally identify fecal pollution sources. A fundamental
      requirement to identify such methods is understanding the microbial and chemical
      processes that influence fate and transport of fecal indicators from various
      sources to receiving streams. Using the Watauga River watershed in northeast
      Tennessee as a model to better understand these processes, multivariate
      statistical analyses were conducted on data collected from four creeks that have
      or are expected to have pathogen TMDLs. The application of canonical correlation
      and discriminant analyses revealed spatial and temporal variability in the
      microbial and chemical parameters influencing water quality, suggesting that
      these creeks differ in terms of the nature and extent of fecal pollution. The
      identification of creeks within a watershed that have similar sources of fecal
      pollution using this data analysis approach could change prioritization of best
      management practices selection and placement. Furthermore, this suggests that
      TMDL development may require multiyear and multisite data using a targeted
      sampling approach instead of a 30-d geometric mean in large, complex watersheds.
      This technique may facilitate the choice between watershed TMDLs and single
      segment or stream TMDLs. 

PMID- 25602571
TI  - Transport of , , and microspheres in biochar-amended soils with different
      textures.
AB  - The incorporation of biochar into soils has been proposed as a means to sequester
      carbon from the atmosphere. An added environmental benefit is that biochar has
      been shown to increase soil retention of agrochemicals, and recent research has
      indicated that biochar may be effective in increasing soil retention of bacteria.
      In this study we investigate the transport behavior of O157:H7, serovar
      Typhimurium, and carboxylated polystyrene microspheres in water-saturated column
      experiments for two soils (fine sand and sandy loam) amended with 2% poultry
      litter or pine chip biochars pyrolyzed at 350 and 700 degrees C. Adding poultry
      litter biochar pyrolyzed at 350 degrees C did not improve soil retention of
      either bacteria in fine sand and even facilitated their transport in sandy loam.
      Addition of either biochar pyrolyzed at 700 degrees C generally improved
      retention of bacteria in fine sand, with the pine chip biochars being more
      effective in limiting their transport. Results from the column studies and
      auxiliary batch studies suggest that changes in cell retention after biochar
      amendments were likely due to changes in bacterial attachment in the column and
      not to physical straining or changes in survivability. We also found that changes
      in bacterial hydrophobicity after biochar amendments were generally correlated
      with changes in bacterial retention. The influence of biochar amendment in
      increasing retention of both bacteria was generally more pronounced in fine sand
      and indicates that soil texture affects the transport behavior of bacteria
      through biochar-amended soils. 

PMID- 25602572
TI  - Arsenic Retention in Foliage and Soil after Monosodium Methyl Arsenate (MSMA)
      Application to Turfgrass.
AB  - Monosodium methyl arsenate (MSMA) is a commonly used herbicide for weed control
      in turfgrass systems. There is concern that arsenic from applied MSMA could leach
      to groundwater or run off into surface water, thereby threatening human and
      ecosystem health. The USEPA has proposed a phase-out of the herbicide but is
      seeking additional research about the toxicity and environmental impacts of MSMA
      before establishing a final ruling. Little research has systematically
      investigated MSMA in field-based settings; instead, risks have been inferred from
      isolated field measurements or model-system studies. Accordingly, the overall
      goal of this study was to quantify the fate of arsenic after MSMA application to
      a managed turfgrass system. After MSMA application to turfgrass-covered and
      bareground lysimeters, the majority of arsenic was retained in turfgrass foliage
      and soils throughout year-long experiments, with 50 to 101% of the applied
      arsenic recovered in turfgrass systems and 55 to 66% recovered in bareground
      systems. Dissolved arsenic concentrations from 76.2-cm-depth pore water in the
      MSMA-treated soils were consistently <2 MUg L, indistinguishable from background
      concentrations. As measured by adsorption isotherm experiments, MSMA retention by
      the sandy soil from our field site was markedly less than retention by a washed
      sand and a clay loam. Collectively, these results suggest that under aerobic
      conditions, minimal arsenic leaching to groundwater would occur after a typical
      application of MSMA to turfgrass. However, repeated MSMA application may pose
      environmental risks. Additional work is needed to examine arsenic cycling near
      the soil surface and to define arsenic speciation changes under different soil
      conditions. 

PMID- 25602573
TI  - Effect of pH on Metal Lability in Drinking Water Treatment Residuals.
AB  - Drinking water treatment residuals (WTRs), by-products generated during treatment
      of drinking water, can be reused as environmental amendments to remediate
      contamination. However, this beneficial reuse may be hampered by the potential
      release of toxic contaminants (e.g., metals) in the WTRs. In present study, batch
      tests and then fractionation, in vitro digestion, and the toxicity characteristic
      leaching procedure were used to investigate the release and extractability of
      metals in the Fe/Al hydroxides comprised WTRs under differing pH. The results
      demonstrated that significant release from WTRs for Ba, Be, Ca, Cd, Co, Cr, Fe,
      Mg, Mn, Pb, Sr, and Zn occurred under low pH (acid condition); for As, Mo, and V
      under high pH (alkaline condition); and for Al, Cu, and Ni under both conditions.
      In comparison, most metals in the WTRs were more easily released under low pH,
      but the release was stable at a relatively low level between pH 6 and 9,
      especially under alkaline conditions. Further analysis indicated that the
      chemical extractability and bioaccessibility of many metals was found to increase
      in the WTRs after being leached, even though the leached WTRs could still be
      considered nonhazardous. These results demonstrated that pH had a substantial
      effect on the lability of metals in WTRs. Overall, caution should be used when
      considering pH conditions during WTRs reuse to avoid potential metal pollution. 

PMID- 25602574
TI  - Effects of dietary protein concentration on ammonia volatilization, nitrate
      leaching, and plant nitrogen uptake from dairy manure applied to lysimeters.
AB  - This lysimeter experiment was designed to investigate the effects of dietary
      crude protein (CP) concentration on nitrate-N (NO-N) and ammonia (NH) losses from
      dairy manure applied to soil and manure N used for plant growth. Lactating dairy
      cows were fed diets with 16.7% CP (HighCP) or 14.8% CP (LowCP) content. Feces and
      urine were labeled with N by ruminal pulse-doses of NHCl. Unlabeled and N-labeled
      feces and urine were used to produce manure for a study with 21 lysimeters in a
      greenhouse. Manure application rate was 277 kg N ha. Ammonia emissions were
      measured at 3, 8, 23, 28, 54, and 100 h after manure application. Manure was
      incorporated into the soil, and a leaching event was simulated. Spring barley was
      planted (387 plants per m) 7 d after the leaching event and harvested at
      senescence. Ammonia emission rates and the contribution of urinary N to NO-N were
      on average about 100% greater for HighCP vs. LowCP manures. With both LowCP and
      HighCP manures, a greater proportion of urinary vs. fecal N was recovered in
      leachate NO-N. There was no difference in whole-crop barley N yields between
      LowCP and HighCP manures, but barley kernel N yield tended to be greater ( =
      0.09) for lysimeters treated with HighCP manures. Using a unique labeling
      approach, this lysimeter experiment demonstrated that when applied at equal soil
      N application rates, manure from cows fed the HighCP diet resulted in markedly
      greater NH emissions and urinary N losses with leachate NO-N than manure from
      cows fed the LowCP diet. 

PMID- 25602575
TI  - Functional Differences between Natural and Restored Wetlands in the Glaciated
      Interior Plains.
AB  - We measured soil properties, carbon and nutrient (nitrogen, phosphorus) pools,
      ambient and potential denitrification, and phosphorus sorption index (PSI) in
      natural depressional wetlands and depressional wetlands restored through the U.S.
      Department of Agriculture (USDA) Wetland Reserve Program. We measured the same
      suite of variables in natural and USDA Conservation Reserve Program-restored
      riparian buffers and in agricultural fields adjacent to both systems to determine
      the degree to which ecosystem services are being provided through restoration in
      different hydrogeomorphic settings. Organic carbon and nutrient pools, PSI, and
      denitrification were greater in natural than in 5- to 10-yr-old restored
      depressional wetlands. In riparian soils, carbon and nutrient pools, PSI, and
      denitrification were comparable between restored and natural systems, suggesting
      that these services develop quickly after restoration. Restored depressional
      wetlands had lower soil organic C, N, and P relative to agricultural soils,
      whereas the opposite trend was observed in restored riparian soils. Four-year-old
      restored riparian buffers achieved equivalence to natural riparian buffers within
      4 yr, whereas restored depressional wetlands took longer to provide these
      ecosystem services (i.e., PSI, denitrification, C storage) at levels comparable
      to natural wetlands. Restored depressional wetlands and riparian buffers provide
      ecosystem services lost through previous conversion to agriculture throughout the
      Midwest; however, the development of these services depends on hydrodynamics
      (pulsed versus nonpulsed), parent material, soil texture (sand, clay), and
      disturbance regime (prescribed fire) of the site. As restoration continues
      throughout the region, C sequestration and nutrient removal in these systems is
      expected to increase water quality at the local and regional levels. 

PMID- 25602576
TI  - Soils and human health.

PMID- 25602578
TI  - Response of growing ruminants to diet in warm climates: a meta-analysis.
AB  - The aim of this work was to establish the response of growing sheep, goats and
      cattle to different nutritional environments. Data from 590 publications
      representing 2225 treatments were analysed. The results showed that each 10%
      increase in NDF was accompanied by 0.11 g/kg live weight (LW) and 0.32 g/kg
      metabolic live weight (LW0.75) decreases in DMI. Otherwise, the response of DMI
      to CP (CP%DM) content was curvilinear (P1.4, corresponding to maximum growth
      (HE+)). No significant difference was observed between LE-- and LE-, and no
      significant difference was observed between ME+- and HE+. For nitrogen balance,
      no difference was observed between species for a given level of nitrogen intake. 

PMID- 25602579
TI  - Preliminary study of high mobility group box chromosomal protein 1(HMGB1) in
      ankylosing spondylitis patients.
AB  - OBJECTIVES: To compare the serum levels of high mobility group box chromosomal
      protein 1 (HMGB1) between patients with AS and healthy controls, and evaluate its
      association with disease activities and functional abilities; to investigate the
      cell surface receptors related to HMGB1 in AS patients. METHODS: The HMGB1 serum
      levels from71 previously untreated AS patients and 40 healthy controls were
      detected by ELISA method. Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing
      Spondylitis Functional Index (BASFI), erythrocytesedimentationrate (ESR), and C
      reactive protein (CRP) levels were assessed on these participants. The mRNA
      expression of HMGB1 and its relevant cell surface receptors RAGE, TLR2, TLR4, and
      IL-1Racp complex were analysed by RT-PCR. RESULTS: The HMGB1 serum levels from AS
      patients were significantly higher than those from healthy controls and
      remarkably positive correlated with BASDAI, ASDAS, BASFI, CRP, and ESR. ASDAS
      showed more correlated to HMGB1 serum levels than BASDAI. Besides, the expression
      of TLR2, TLR4, and IL-1Racp from PBMCs revealed significant correlations with the
      expression of HMGB1. CONCLUSIONS: HMGB1 might be a good laboratory index for the
      evaluation of disease activities and disease severity in AS patients. Further,
      extracellular HMGB1 play its inflammatory role mainly via the expression of cell
      surface receptors TLR2, TLR4 and IL-1RAcP complex.

PMID- 25602577
TI  - Auditory deficits of Kcna1 deletion are similar to those of a monaural hearing
      impairment.
AB  - Kv1.1 subunits of low voltage-activated (Kv) potassium channels are encoded by
      the Kcna1 gene and crucially determine the synaptic integration window to control
      the number and temporal precision of action potentials in the auditory brainstem
      of mammals and birds. Prior electrophysiological studies showed that auditory
      signaling is compromised in monaural as well as in binaural neurons of the
      auditory brainstem in Kv1.1 knockout mice (Kcna1(-/-)). Here we examine the
      behavioral effects of Kcna1 deletion on sensory tasks dependent on either
      binaural processing (detecting the movement of a sound source across the
      azimuth), monaural processing (detecting a gap in noise), as well as binaural
      summation of the acoustic startle reflex (ASR). Hearing thresholds measured by
      auditory brainstem responses (ABR) do not differ between genotypes, but our data
      show a much stronger performance of wild type mice (+/+) in each test during
      binaural hearing which was lost by temporarily inducing a unilateral hearing loss
      (through short term blocking of one ear) thus remarkably, leaving no significant
      difference between binaural and monaural hearing in Kcna1(-/-) mice. These data
      suggest that the behavioral effect of Kv1.1 deletion is primarily to impede
      binaural integration and thus to mimic monaural hearing. 

PMID- 25602581
TI  - Feasibility and acceptability of web-based enhanced relapse prevention for
      bipolar disorder (ERPonline): trial protocol.
AB  - BACKGROUND: Relapse prevention interventions for Bipolar Disorder are effective
      but implementation in routine clinical services is poor. Web-based approaches
      offer a way to offer easily accessible access to evidence based interventions at
      low cost, and have been shown to be effective for other mood disorders.
      METHODS/DESIGN: This protocol describes the development and feasibility testing
      of the ERPonline web-based intervention using a single blind randomised
      controlled trial. Data will include the extent to which the site was used,
      detailed feedback from users about their experiences of the site, reported
      benefits and costs to mental health and wellbeing of users, and costs and savings
      to health services. We will gain an estimate of the likely effect size of
      ERPonline on a range of important outcomes including mood, functioning, quality
      of life and recovery. We will explore potential mechanisms of change, giving us a
      greater understanding of the underlying processes of change, and consequently how
      the site could be made more effective. We will be able to determine rates of
      recruitment and retention, and identify what factors could improve these rates.
      DISCUSSION: The findings will be used to improve the site in accordance with user
      needs, and inform the design of a large scale evaluation of the clinical and cost
      effectiveness of ERPonline. They will further contribute to the growing evidence
      base for web-based interventions designed to support people with mental health
      problems.

PMID- 25602580
TI  - Extended-release naltrexone to prevent relapse among opioid dependent, criminal
      justice system involved adults: rationale and design of a randomized controlled
      effectiveness trial.
AB  - BACKGROUND: Extended-release naltrexone (XR-NTX, Vivitrol; Alkermes Inc.) is an
      injectable monthly sustained-release mu opioid receptor antagonist. XR-NTX is a
      potentially effective intervention for opioid use disorders and as relapse
      prevention among criminal justice system (CJS) populations. METHODS: This 5-site
      open-label randomized controlled effectiveness trial examines whether XR-NTX
      reduces opioid relapse compared with treatment as usual (TAU) among community
      dwelling, non-incarcerated volunteers with current or recent CJS involvement. The
      XR-NTX arm receives 6 monthly XR-NTX injections at Medical Management visits; the
      TAU group receives referrals to available community treatment options.
      Assessments occur every 2 weeks during a 24-week treatment phase and at 12- and
      18-month follow-ups. The primary outcome is a relapse event, defined as either
      self-report or urine toxicology evidence of >=10 days of opioid use in a 28-day
      (4 week) period, with a positive or missing urine test counted as 5 days of
      opioid use. RESULTS: We describe the rationale, specific aims, and design of the
      study. Alternative design considerations and extensive secondary aims and
      outcomes are discussed. CONCLUSIONS: XR-NTX is a potentially important treatment
      and relapse prevention option among persons with opioid dependence and CJS
      involvement. ClinicalTrials.gov: NCT00781898.

PMID- 25602582
TI  - Predictive dose-based estimation of systemic exposure multiples in mouse and
      monkey relative to human for antisense oligonucleotides with 2'-o-(2
      methoxyethyl) modifications.
AB  - Evaluation of species differences and systemic exposure multiples (or ratios) in
      toxicological animal species versus human is an ongoing exercise during the
      course of drug development. The systemic exposure ratios are best estimated by
      directly comparing area under the plasma concentration-time curves (AUCs), and
      sometimes by comparing the dose administered, with the dose being adjusted either
      by body surface area (BSA) or body weight (BW). In this study, the association
      between AUC ratio and the administered dose ratio from animals to human were
      studied using a retrospective data-driven approach. The dataset included nine
      antisense oligonucleotides (ASOs) with 2'-O-(2-methoxyethyl) modifications,
      evaluated in two animal species (mouse and monkey) following single and repeated
      parenteral administrations. We found that plasma AUCs were similar between ASOs
      within the same species, and are predictable to human exposure using a single
      animal species, either mouse or monkey. Between monkey and human, the plasma
      exposure ratio can be predicted directly based on BW-adjusted dose ratios,
      whereas between mouse and human, the exposure ratio would be nearly fivefold
      lower in mouse compared to human based on BW-adjusted dose values. Thus,
      multiplying a factor of 5 for the mouse BW-adjusted dose would likely provide a
      reasonable AUC exposure estimate in human at steady-state. 

PMID- 25602583
TI  - Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA.
AB  - Using pre-miR-451 as a model molecule, we have characterized the general
      molecular properties of small hairpin RNAs that are processed into potent small
      interfering RNAs (siRNA) by Argonaute2 (Ago2). The Ago2-sliced siRNAs (sli
      siRNAs) have the same silencing potency as the classical Dicer diced siRNAs (di
      siRNAs) but have dramatically reduced unwanted sense strand activities. We have
      built vectors with the constitutive or inducible U6 promoter that can express sli
      siRNAs in mammalian cells, in which the sli-siRNAs can be correctly processed to
      repress target genes. As a proof of principle for potential applications of sli
      siRNAs in vivo, we show that the expression of one Ago2 shRNA-1148 in HCT-116
      colon cancer cells knocked down RRM2 expression and reduced the proliferation and
      invasiveness of the cells. The defined sli-siRNA model molecules and the
      expression systems established in this study will facilitate the design and
      application of sli-siRNAs as novel potent RNAi triggers with reduced off-target
      effects. 

PMID- 25602584
TI  - Using medical incidents to teach: effects of vicarious experience on nursing
      students' self-efficacy in performing urinary catheterization.
AB  - This study compared the effects of instruction on nursing students' self-efficacy
      in urinary catheterization, using positively and negatively worded examples after
      vicarious experience of a medical incident. Nursing students (n = 128) completed
      measures on urinary catheterization performance, general self-efficacy, and self
      efficacy in urinary catheterization before being assigned to one of three groups:
      the instruction with negative examples (NE), the instruction with positive
      examples (PE), or the control group. Each group read the same medical incident.
      The instruction with NE and PE groups read negatively and positively worded
      examples, respectively, about urinary catheterization, and the control group read
      a summary of the incident. All students indicated their self-efficacy in urinary
      catheterization. A statistically significant increase in self-efficacy was noted
      in the PE and NE groups but was significantly higher in the NE group, compared
      with the control group. Implications for nurse educators using medical incidents
      to increase nursing students' self-efficacy are discussed.

PMID- 25602585
TI  - Onboarding new adjunct clinical nursing faculty using a quality and safety
      education for nurses-based orientation model.
AB  - In light of the nursing faculty shortage, many clinical nurses are transitioning
      to adjunct clinical faculty roles. This transition requires formal orientation
      programs that are based on an established framework that links academic and
      practice competencies. The authors propose that linking academic and practice
      competencies will enhance students' education and promote patient safety. The
      model described in this article uses the Quality and Safety Education for Nurses
      (QSEN) competencies to design and deliver an onboarding orientation model for new
      adjunct clinical faculty. For each QSEN competency, orientation topics, learning
      objectives for new faculty, and orientation activities are offered. This model
      serves as a template on which new adjunct clinical faculty can be onboarded, thus
      lessening role-transition stressors. Adequately prepared adjunct clinical faculty
      offer students a clinical expert who has received an orientation built on the
      QSEN competencies.

PMID- 25602586
TI  - Model for teaching population health and community-based care across diverse
      clinical experiences.
AB  - The pillars constructivist model is designed to offer a unifying clinical
      paradigm to support consistent learning opportunities across diverse
      configurations of community and public health clinical sites. Thirty-six students
      and six faculty members participated in a mixed methods evaluation to assess the
      model after its inaugural semester of implementation. The evaluation methods
      included a rating scale that measures the model's ability to provide consistent
      learning opportunities at both population health and direct care sites, a case
      study to measure student growth within the five conceptual pillars, and a faculty
      focus group. Results revealed that the model served as an effective means of
      clinical education to support the use of multiple, small-scale public health
      sites. Although measurements of student growth within the pillars are
      inconclusive, the findings suggest efficacy. The authors recommend the continued
      use of the pillars constructivist model in baccalaureate programs, with further
      study of the author-designed evaluation tools.

PMID- 25602587
TI  - Objective structured video examination in psychiatric and mental health nursing:
      a learning and assessment method.
AB  - In the current study, the Objective Structured Video Examination (OSVE) was
      conducted to assess undergraduate nursing students' knowledge, observation, and
      clinical reasoning related to clinical psychiatric nursing competencies. The OSVE
      showed acceptable reliability and validity (Cronbach's alpha = 0.714, r = 0.6,
      respectively). Students highly appraised the OSVE because it covered a wide area
      of knowledge and clinical skills; the examination instructions were clear,
      concrete, and easily understood; the sounds and pictures of the videos were
      clear; and the videos simulated real patients. The examination was fair, well
      administered, well-structured, and well-sequenced. The OSVE reflected learned
      skills, it provided opportunities for learning, grades were clearly identified,
      and it eliminated personal bias. Overall, the OSVE provided a practical and
      useful experience. On the other hand, some students negatively perceived the OSVE
      as being stressful and requiring more time.

PMID- 25602588
TI  - Black African nurses educated in the United States.
AB  - Black Africans are one of the fastest growing immigrant and refugee populations
      in the United States, having increased by 100% in the 2000s. The purpose of this
      study was to gain an understanding of how Black African nurses experience nursing
      education within the United States. This qualitative study provided a rich
      description of the phenomenon. Nine Black African nurses from the midwestern
      United States participated. Five male and four female participants represented
      the countries of Sierra-Leone, Kenya, Liberia, Eritrea, and Ethiopia. Seven
      participants had been in the country less than 2 years, and two had been in the
      country less than 4 years. Optimistic determination was the essence of how
      participants adapted to challenges while in their nursing programs, and four
      themes emerged relating to academics, competing demands, culture, and
      relationships. Through an awareness of the unique needs of this student
      population, educators can develop strategies to improve retention.

PMID- 25602589
TI  - Unfolding case studies as a formative teaching methodology for novice nursing
      students.
AB  - Nurse educators are challenged to incorporate evidence-based practice initiatives
      into content-laden curricula in a manner that supports learner-centered teaching
      environments. This article describes a technique for using unfolding case studies
      to include such initiatives in the teaching of novice nursing students, as
      opposed to summative evaluation of their knowledge. Modeled after Kolb's
      experiential learning theory, a framework for unfolding case studies is
      presented, which proposes that instead of faculty selecting scenarios for
      students, they should instead challenge students to directly and creatively
      develop their own. Small student groups used creative collaboration to create
      well-planned, complex case study scenarios that unfolded in surprising, realistic
      ways. This instructional method was met with positive student feedback; however,
      the authors suggest several recommendations for educators considering this
      approach. The authors found this framework to be a successful and effective
      strategy for undergraduate novice nursing students.

PMID- 25602590
TI  - The role of lamin B1 for the maintenance of nuclear structure and function.
AB  - Lamins constitute an integral structural component of the nuclear lamina.
      However, their impact on the structure and stability of chromosome territories,
      and on the regulation of gene expression is explored to a lesser extent. By 3D
      FISH, Camps and colleagues showed that lamin B1 (LMNB1) is required for proper
      chromosome condensation in interphase nuclei, and deficiency of LMNB1 triggers
      the relocation of the epigenetic mark of facultative heterochromatin, H3K27me3,
      toward the interior of the nucleus. Additionally, LMNB1 repression slowed
      cellular growth due to S-phase delays and increased genomic instability. Finally,
      silencing of LMNB1 resulted in enlarged nuclear speckles and in extensive changes
      in alternative splicing of multiple genes. Altogether, the data suggest a central
      role of LMNB1 for the condensation of chromosome territories, for the
      distribution of heterochromatin, and for the regulation of gene expression and
      splicing. 

PMID- 25602591
TI  - Thermal expansivities of peptides, polypeptides and proteins as measured by
      pressure perturbation calorimetry.
AB  - The main goal of this work was to provide direct experimental evidence that the
      expansivity of peptides, polypeptides and proteins as measured by pressure
      perturbation calorimetry (PPC), can serve as a proxy to characterize relative
      compactness of proteins, especially the denatured state ensemble. This is very
      important as currently only small angle X-ray scattering (SAXS), intrinsic
      viscosity and, to a lesser degree, fluorescence resonance transfer (FRET)
      experiments are capable of reporting on the compactness of denatured state
      ensembles. We combined the expansivity measurements with other biophysical
      methods (far-UV circular dichroism spectroscopy, differential scanning
      calorimetry, and small angle X-ray scattering). Three case studies of the effects
      of conformational changes on the expansivity of polypeptides in solution are
      presented. We have shown that expansivity appears to be insensitive to the helix
      coil transition, and appears to reflect the changes in hydration of the side
      chains. We also observed that the expansivity is sensitive to the global
      conformation of the polypeptide chain and thus can be potentially used to probe
      hydration of different collapsed states of denatured or even intrinsically
      disordered proteins. 

PMID- 25602592
TI  - S-K Smartphone Barcode Reader for the Blind.
AB  - We describe a new smartphone app called BLaDE (Barcode Localization and Decoding
      Engine), designed to enable a blind or visually impaired user find and read
      product barcodes. Developed at The Smith-Kettlewell Eye Research Institute, the
      BLaDE Android app has been released as open source software, which can be used
      for free or modified for commercial or non-commercial use. Unlike popular
      commercial smartphone apps, BLaDE provides real-time audio feedback to help
      visually impaired users locate a barcode, which is a prerequisite to being able
      to read it. We describe experiments performed with five blind/visually impaired
      volunteer participants demonstrating that BLaDE is usable and that the audio
      feedback is key to its usability.

PMID- 25602593
TI  - Can NASH lipidome provide insight into the pathogenesis of obesity-related non
      alcoholic fatty liver disease?

PMID- 25602594
TI  - Predictors of Youths' Posttraumatic Stress Symptoms Following a Natural Disaster:
      The 2010 Nashville, Tennessee, Flood.
AB  - Framed by a previously established conceptual model of youths' posttraumatic
      stress (PTS) responses following a disaster, the current longitudinal study
      examined the relation of predisaster child characteristics (age, gender,
      depressive symptoms, ruminative coping), predisaster environmental
      characteristics (negative life events and supportive and negative friendship
      interactions), and level of disaster exposure to youths' PTS symptoms in the wake
      of a natural disaster. Prior to the 2010 Nashville, Tennessee, flood, 239
      predominantly Caucasian youth from four elementary and middle schools (ages = 10
      15, 56% girls) completed measures of depressive symptoms, rumination, negative
      life events, and social support in the form of both supportive and negative
      friendship interactions. Approximately 10 days after returning to school, 125
      completed measures of disaster exposure and postflood PTS symptoms. Bivariate
      correlations revealed that disaster-related PTS symptoms were unrelated to age,
      gender, or predisaster supportive friendship interactions and significantly
      positively related to level of disaster exposure and predisaster levels of
      negative life events, depressive symptoms, rumination, and negative friendship
      interactions. After controlling for level of disaster exposure and other
      predisaster child and environmental characteristics, depressive symptoms and
      negative friendship interactions predicted postdisaster PTS symptoms. The effect
      of child's flood-related experiences on PTS symptoms was not moderated by any of
      the preexisting child characteristics or environmental indicators. Faced with
      limited resources after a natural disaster, school counselors and other health
      professionals should focus special attention on youths who experienced high
      levels of disaster-related losses and whose predisaster emotional and
      interpersonal lives were problematic. 

PMID- 25602595
TI  - A health risk assessment of Arabian incense (Bakhour) smoke in the United Arab
      Emirates.
AB  - Burning Arabian incense (Bakhour) is a common practice in the Middle East and
      Arabian Gulf. Although the incense generates large amounts of chemicals and air
      pollutants, little is known with regard to the nature of these chemicals and
      their potential health risks. The aim of this study is to provide a comprehensive
      characterization of the chemical constituents emitted in Bakhour smoke, and
      subsequently to examine the associated health implications of these components.
      Thermo-gravimetric analysis was used to investigate the presence and the thermal
      profile of volatile organic compounds in three different samples of Bakhour
      smoke. Thermal desorption-gas chromatography-mass spectrometry was then applied
      to isolate all the volatile and semi-volatile compounds present in the Bakhour
      smoke samples. Using a spectral library and an extensive literature search, all
      organic compounds detected were analyzed for potential health risks. A total of
      859 compounds were emitted from burning the different Bakhour samples. The novel
      finding of this research shows that 42 detected compounds are suspected/known
      carcinogens, 20 are known to have toxic effects, and at least 200 compounds are
      known irritants to the eyes, skin, respiratory and digestive tracts, as reported
      in human and/or animal studies. Our study suggests that inhaled Bakhour smoke
      contains a substantial number of adverse compounds, which are known to be
      detrimental to human health. Moreover, the evidence presented shows that incense
      burning is a significant source of environmental pollution; with the potential of
      significant health concerns particularly with long term exposure. As the majority
      of the compounds detected have no reported clinical data, there is an urgent need
      for significant research in this field. 

PMID- 25602596
TI  - Comparative study of sliced tragal cartilage and temporalis fascia in type I
      tympanoplasty.
AB  - OBJECTIVE: To compare anatomical and audiological results using sliced tragal
      cartilage and temporalis fascia in type I tympanoplasty. METHOD: A retrospective
      review was undertaken of primary tympanoplasties using sliced tragal cartilage
      and temporalis fascia from May 2005 to January 2008. In total, 223 ears were
      operated on using sliced tragal cartilage graft and 167 using temporalis fascia.
      Statistical analysis of the outcome data was performed. RESULTS: At the two-year
      and four-year follow ups, successful closure of the tympanic membrane was
      achieved in 98.20 per cent and 97.75 per cent, respectively, of the cartilage
      group compared with 87.42 per cent and 82.63 per cent, respectively, of the
      temporalis fascia group. At the four-year follow up, the average air-bone gap was
      7.10 +/- 3.01 dB in the cartilage group and 8.05 +/- 3.22 dB in the temporalis
      fascia group. CONCLUSION: The overall success rate for primary cartilage
      tympanoplasty is higher when using sliced cartilage than with temporalis fascia
      grafting.

PMID- 25602597
TI  - Coronary artery disease and transcatheter aortic valve replacement: current
      treatment paradigms.
AB  - Aortic stenosis is the most common form of valvular heart disease in the elderly
      population and is often diagnosed in individuals who also have coronary artery
      disease. Surgical aortic valve replacement has been the standard of care for the
      treatment of aortic stenosis during the past decades, but the availability of
      transcatheter aortic valve replacement has now allowed different options for high
      or extreme surgical risk patients. The management of coronary artery disease in
      patients undergoing transcatheter aortic valve replacement remains a
      controversial issue, as available studies in the literature have generated
      conflicting results. This review offers a comprehensive portrait of coronary
      artery disease management in the presence of concomitant aortic stenosis and
      proposes treatment approaches for patients presenting both diseases. 

PMID- 25602598
TI  - Nature of AX centers in antimony-doped cadmium telluride nanobelts.
AB  - Single crystalline p-type CdTe:Sb nanobelts were fabricated using an Au-catalyzed
      chemical vapor deposition method. Low carrier concentration and low mobility even
      at high Sb incorporation manifest compensation in the system. From cross
      examination of temperature-dependent charge transport and photoluminescence
      measurements, two major acceptor levels induced by Sb doping are determined: a
      shallow level attributed to substitutional Sb dopants without lattice relaxation
      and an associated deeper level resulted from large lattice relaxation-AX centers.
      Persistent photoconductivity and hysteresis photoconductance under the thermal
      cycle elucidate the nature of AX centers. This comprehensive investigation of the
      impurity levels in the material system is essential for the design and
      development of nanoelectronic devices based on the CdTe nanostructures. 

PMID- 25602599
TI  - Copper-organic cationic ring with an inserted arsenic-vanadium polyanionic
      cluster for efficient catalytic Cr(VI) reduction using formic acid.
AB  - Polyanionic cluster [beta-As8V14O42(H2O)](4-) is well embedded in a large porous
      eight-membered cationic ring of the copper ligand, giving a stable host-guest
      supramolecular system. The assembly exhibits an efficient heterogeneous catalytic
      performance for the reduction of Cr(VI) using formic acid at ambient temperature.

PMID- 25602600
TI  - A low pulse food intake may contribute to the poor nutritional status and low
      dietary intakes of adolescent girls in rural southern Ethiopia.
AB  - Poor nutrition in adolescent girls poses critical health risks on future
      pregnancy and birth outcomes especially in developing countries. Our purpose was
      to assess nutritional status and dietary intake of rural adolescent girls and
      determine pulse and food intake patterns associated with poor nutritional status.
      A cross-sectional community-based study was conducted in a traditional pulse
      growing region of southern Ethiopia on 188 girls between 15 to 19 years of age,
      with 70% being from food insecure families. Prevalence of stunting (30.9%) and
      underweight (13.3%) were associated with low food and nutrient intake. Diets were
      cereal-based, with both animal source foods and pulses rarely consumed. Improving
      dietary intakes of female adolescents with nutrient dense foods would ensure
      better health for themselves and for the next generation. 

PMID- 25602601
TI  - Directed Growth of Virus Nanofilaments on a Superhydrophobic Surface.
AB  - The evaporation of single droplets of colloidal tobacco mosaic virus (TMV)
      nanoparticles on a superhydrophobic surface with a hexagonal pillar-pattern
      results in the formation of coffee-ring type residues. We imaged surface features
      by optical, scanning electron, and atomic force microscopies. Bulk features were
      probed by raster-scan X-ray nanodiffraction. At ~100 pg/MUL nanoparticle
      concentration, the rim of the residue connects to neighboring pillars via fibrous
      extensions containing flow-aligned crystalline domains. At ~1 pg/MUL nanoparticle
      concentration, nanofilaments of >=80 nm diameter and ~20 MUm length are formed,
      extending normal to the residue-rim across a range of pillars. X-ray scattering
      is dominated by the nanofilament form-factor but some evidence for crystallinity
      has been obtained. The observation of sheets composed of stacks of self-assembled
      nanoparticles deposited on pillars suggests that the nanofilaments are drawn from
      a structured droplet interface. 

PMID- 25602602
TI  - Persistent high IgG phase I antibody levels against Coxiella burnetii among
      veterinarians compared to patients previously diagnosed with acute Q fever after
      three years of follow-up.
AB  - BACKGROUND: Little is known about the development of chronic Q fever in
      occupational risk groups. The aim of this study was to perform long-term follow
      up of Coxiella burnetii seropositive veterinarians and investigate the course of
      IgG phase I and phase II antibodies against C. burnetii antigens and to compare
      this course with that in patients previously diagnosed with acute Q fever.
      METHODS: Veterinarians with IgG phase I >= 1:256 (immunofluorescence assay) that
      participated in a previous seroprevalence study were asked to provide a second
      blood sample three years later. IgG antibody profiles were compared to a group of
      acute Q fever patients who had IgG phase I >= 1:256 twelve months after
      diagnosis. RESULTS: IgG phase I was detected in all veterinarians (n = 76) and in
      85% of Q fever patients (n = 98) after three years (p<0.001). IgG phase I >=
      1:1,024, indicating possible chronic Q fever, was found in 36% of veterinarians
      and 12% of patients (OR 3.95, 95% CI: 1.84-8.49). CONCLUSIONS: IgG phase I
      persists among veterinarians presumably because of continuous exposure to C.
      burnetii during their work. Serological and clinical follow-up of occupationally
      exposed risk groups should be considered.

PMID- 25602603
TI  - Is training effective? A study of counseling psychology doctoral trainees in a
      psychodynamic/interpersonal training clinic.
AB  - We investigated changes over 12 to 42 months in 23 predoctoral trainees during
      their externship training in a psychodynamic/interpersonal psychotherapy clinic.
      Over time, trainees increased in client-rated working alliance and real
      relationship, therapist-rated working alliance, client-rated interpersonal
      functioning, ability to use helping skills (e.g., challenges, immediacy), higher
      order functioning (e.g., conceptualization ability, countertransference
      management), feelings about themselves as therapists (e.g., more authentic, more
      self-aware), and understanding about being a therapist (e.g., theoretical
      orientation, curiosity about client dynamics). In contrast, trainees did not
      change in engaging clients (return after intake or for at least 8 sessions),
      judge-rated psychodynamic techniques in third and ninth sessions across clients
      (although trainees used more cognitive-behavioral techniques over time in third
      but not ninth sessions), or changes in client-rated symptomatology. Trainees
      primarily attributed changes to graduate training, individual and group
      supervision, research participation, and working with clients. Implications for
      training and research are discussed.

PMID- 25602604
TI  - Development and validation of the Patriarchal Beliefs Scale.
AB  - The purpose of this research was to develop and validate a conceptually and
      psychometrically solid measure for patriarchal beliefs in samples of U.S.
      American adults from diverse demographic and geographic backgrounds. In Study 1,
      we identified 3 correlated factors of the Patriarchal Beliefs Scale (PBS) in data
      collected from the Internet (N = 279): Institutional Power of Men, Inferiority of
      Women, and Gendered Domestic Roles. In Study 2, data collected from the Internet
      (N = 284) supported both an oblique 3-factor structure and a bifactor structure
      of the PBS, through confirmatory factor analyses. Construct validity of the PBS
      was supported in relation to other gender-related measures. The PBS was
      correlated in expected directions with modern sexism, antifeminist attitudes, and
      egalitarian attitudes toward women. In Study 3, we examined measurement
      invariance across gender by using combined data from Study 1 and Study 2. All 3
      factors of the oblique 3-factor model indicated measurement invariance, whereas
      the general factor represented in the bifactor model indicated nonequivalence.
      Mean differences in patriarchal beliefs were found for such demographic variables
      as gender, sexual orientation, education, and social class. Recommendations for
      using the PBS, as well as implications for research and practice, are discussed.

PMID- 25602605
TI  - Structured supervision of graduate clinicians in psychodynamic psychotherapy:
      alliance and technique.
AB  - This is the first study to examine longitudinal differences in alliance and
      technique across multiple cases, controlling for client distress and therapist
      effects, during structured supervision in psychodynamic psychotherapy. Patient
      and therapist ratings of alliance as well as independent clinical ratings of
      psychodynamic interventions were assessed during the 3rd and 9th sessions in the
      psychotherapy of 58 outpatients, conducted by 24 graduate clinicians. Findings
      demonstrated that patient-rated alliance was higher across cases at both the 3rd
      and 9th sessions. These differences in alliance were paralleled by trainees'
      using significantly more psychodynamic techniques across cases during the 3rd
      session. All of these differences were in evidence, controlling for patient level
      of pathology. It is also important to note that there were no significant
      differences during the course of training for cognitive-behavioral techniques.
      This is consistent with the specific supervision provided to the graduate
      clinicians in this training practicum. Practical implications for the use of
      structured clinical training and issues pertinent to supervision in graduate
      education are reviewed. Finally, the relationship that structured training may
      have to graduate clinicians' ability to form a positive alliance with their
      patients is also discussed.

PMID- 25602606
TI  - Racial/ethnic discrimination, posttraumatic stress symptoms, and alcohol problems
      in a longitudinal study of Hispanic/Latino college students.
AB  - Racial/ethnic discrimination has been identified as a risk factor in the
      development of posttraumatic stress disorder (PTSD) symptoms in persons of color
      (Carter, 2007). Many persons, regardless of race/ethnicity, with PTSD symptoms
      resulting from combat, violent crimes, sexual assault, or natural disasters use
      alcohol in an attempt to cope. This longitudinal study surveyed 203
      Hispanic/Latino students twice at approximately a 1-year interval, and used a
      cross-lagged design to compare Time 1 links from alcohol use and experiences of
      discrimination with the same variables at Time 2, plus symptoms of PTSD. Each
      survey included the General Ethnic Discrimination scale and the Alcohol Use
      Disorders Identification Test. Only Time 2 packets contained the Posttraumatic
      Stress Disorder Checklist-Civilian. Cross-lagged analyses conducted by comparing
      nested structural equation models found that fixing the causal paths to zero from
      Time 1 experiences of discrimination to Time 2 alcohol problems and PTSD resulted
      in a significantly worse fit of the data. However, fixing the paths to zero from
      Time 1 maladaptive alcohol use to Time 2 PTSD and experiences of discrimination
      resulted in no significant difference in model fit. Thus, this pattern of
      findings is consistent with an inference that Hispanic/Latino college students
      who experience racial/ethnic discrimination are at risk for developing symptoms
      of posttraumatic stress and increased maladaptive alcohol use; conversely,
      maladaptive alcohol use does not appear to be a risk factor for later experiences
      of discrimination or PTSD symptoms.

PMID- 25602607
TI  - Enhancing psychological capital and personal growth initiative: working on
      strengths or deficiencies.
AB  - Personal growth initiative (PGI), defined as being proactive about one's personal
      development, is critical to graduate students' academic success. Prior research
      has shown that students' PGI can be enhanced through interventions that focus on
      stimulating developmental activities. Within this study, we aimed to investigate
      whether an intervention that stimulates development in the area of one's personal
      strengths (strengths intervention) has more beneficial effects on students' PGI
      than an intervention that stimulates development in the area of individual
      deficiencies (deficiency intervention). We conducted 2 longitudinal field
      experiments to investigate the effects of the 2 interventions on students' PGI
      (Experiment 1) and the potential mediating role of psychological capital (PsyCap)
      in this regard (Experiment 2). In Experiment 1, 105 (N = 105) university students
      participated in either a strengths intervention or a deficiency intervention.
      Results indicated that the strengths intervention increased the students' PGI in
      the short but not in the long term, whereas the deficiency intervention did not
      affect PGI. Ninety students (N = 90) participated in Experiment 2, in which we
      slightly refined both interventions by putting a stronger emphasis on the ongoing
      development of strengths (strengths intervention) or correction of deficiencies
      (deficiency intervention) by adding posttraining assignments. Results suggested
      that participating in both interventions led to increases in PGI over a 3-month
      period, but that these increases were bigger for the strengths intervention
      group. Furthermore, the relationship between the strengths intervention and PGI
      was mediated by hope as one component of PsyCap.

PMID- 25602608
TI  - How group factors affect adolescent change talk and substance use outcomes:
      implications for motivational interviewing training.
AB  - Clients who verbalize statements arguing for change (change talk [CT]) in
      psychotherapy are more likely to decrease alcohol and other drug use (AOD)
      compared with clients who voice statements in opposition of change (sustain talk
      [ST]). Little is known about how CT and ST are expressed in groups in which
      adolescents may vary in their AOD use severity and readiness to change. First, we
      examined how session content was associated with CT/ST, and then we looked at
      whether different subtypes of CT/ST were associated with subsequent AOD outcomes
      3 months later. Audio recordings (N = 129 sessions) of a 6-session group
      motivational interviewing (MI) intervention, Free Talk, were coded. Session
      content was not associated with CT; however, some session content was associated
      with higher percentages of ST (e.g., normative feedback). Subtypes of CT
      (Commitment and Reason) were associated with improved AOD outcomes, whereas
      Ability subtype remarks were related to increased marijuana use, intentions, and
      consequences. Findings offer helpful guidance for clinical training and narrow in
      on the type of CT to try to elicit in Group MI sessions. Regardless of session
      content, adolescents can benefit from hearing CT during the group.

PMID- 25602609
TI  - Religious coping moderates the relation between racism and psychological well
      being among Christian Asian American college students.
AB  - The authors examined the moderating role of positive and negative religious
      coping in the relation between racism and psychological well-being in a sample of
      Catholic and Protestant Asian American college students (N = 107). On the basis
      of prior theorizing on the 2 types of religious coping, combined with some
      limited empirical evidence, they predicted that positive religious coping would
      have a buffering effect (Hypothesis 1) on the racism-mental health relation and
      that negative religious coping would have an exacerbating effect (Hypothesis 2).
      Participants completed an online survey containing measures corresponding to the
      study variables. Results indicated that the interaction between positive
      religious coping and racism was nonsignificant, so Hypothesis 1 was not
      supported. For Hypothesis 2, the negative religious coping and racism interaction
      term was statistically significant, but the moderating effect was in an
      unexpected direction, such that negative religious coping actually protected
      against the deleterious impact of racism on mental health. The findings suggest
      that the theorized deleterious influence of negative religious coping may need to
      be reconsidered in an Asian American setting. The findings have the potential to
      inform practitioners who work with Asian American college students to better cope
      with the detrimental consequences of racism.

PMID- 25602610
TI  - Correction to hook, davis, owen, worthington, and utsey.
AB  - Reports an error in "Cultural humility: Measuring openness to culturally diverse
      clients" by Joshua N. Hook, Don E. Davis, Jesse Owen, Everett L. Worthington Jr.
      and Shawn O. Utsey (Journal of Counseling Psychology, 2013[Jul], Vol 60[3], 353
      366). A syntax error was made when calculating the cultural humility total score.
      Instead of calculating the score with 12 items, the total score was calculated
      with 13 items (the 12 correct items plus one incorrect item). The two total
      scores are very similar (correlations between the two are above .99 in all three
      samples); however, the mean is higher due to the extra item added. All of the
      results are almost identical, and none of the conclusions in the article changed.
      The corrected statistics are included in the erratum. (The following abstract of
      the original article appeared in record 2013-15106-001.) Building on recent
      theory stressing multicultural orientation, as well as the development of virtues
      and dispositions associated with multicultural values, we introduce the construct
      of cultural humility, defined as having an interpersonal stance that is other
      oriented rather than self-focused, characterized by respect and lack of
      superiority toward an individual's cultural background and experience. In 4
      studies, we provide evidence for the estimated reliability and construct validity
      of a client-rated measure of a therapist's cultural humility, and we demonstrate
      that client perceptions of their therapist's cultural humility are positively
      associated with developing a strong working alliance. Furthermore, client
      perceptions of their therapist's cultural humility were positively associated
      with improvement in therapy, and this relationship was mediated by a strong
      working alliance. We consider implications for research, practice, and training.
      (PsycINFO Database Record (c) 2015 APA, all rights reserved). 

PMID- 25602612
TI  - Molecular characterization of the cold- and heat-induced Arabidopsis PXL1 gene
      and its potential role in transduction pathways under temperature fluctuations.
AB  - LRR-RLK (Leucine-Rich Repeat Receptor-Like Kinase) proteins are believed to play
      essential roles in cell-to-cell communication during various cellular processes
      including development, hormone perception, and abiotic stress responses. We
      isolated an LRR-RLK gene previously named Arabidopsis PHLOEM INTERCALATED WITH
      XYLEM-LIKE 1 (AtPXL1) and examined its expression patterns. AtPXL1 was highly
      induced by cold and heat stress, but not by drought. The fluorescence signal of
      35S::AtPXL1-EGFP was closely localized to the plasma membrane. A yeast two-hybrid
      and bimolecular fluorescence complementation assay exhibited that AtPXL1
      interacts with both proteins, A. thaliana histidine-rich dehydrin1 (AtHIRD1) and
      A. thaliana light-harvesting protein complex I (AtLHCA1). We found that AtPXL1
      possesses autophosphorylation activity and phosphorylates AtHIRD1 and AtLHCA1 in
      an in vitro assay. Subsequently, we found that the knockout line (atpxl1) showed
      hypersensitive phenotypes when subjected to cold and heat during the germination
      stage, while the AtPXL1 overexpressing line as well as wild type plants showed
      high germination rates compared to the knockout plants. These results provide an
      insight into the molecular function of AtPXL1 in the regulation of signal
      transduction pathways under temperature fluctuations. 

PMID- 25602613
TI  - Robust polydiacetylene-based colorimetric sensing material developed with amyloid
      fibrils of alpha-synuclein.
AB  - Robust polydiacetylene-based colorimetric sensing material has been developed
      with amyloid fibrils of alpha-synuclein in the presence of 10,12-pentacosadiynoic
      acid (PCDA) by taking advantage of the specific fatty acid interaction of alpha
      synuclein and structural regularity of the self-assembled product of amyloid
      fibrils. PCDA facilitated not only self-oligomerization of alpha-synuclein but
      also its fibrillation into the fibrils with increased thickness. Upon UV
      irradiation, the PCDA-containing amyloid fibrils (AF-PCDAs) turned blue, which
      then became red following heat treatment. The blue-to-red color transition was
      also observed with other stimuli of pH and ethanol. AF-PCDAs were demonstrated to
      be mechanically stable since not only the individual colors of blue and red but
      also their colorimetric transition were not affected by a number of sonications
      which readily disrupted the polydiaceylene (PDA) vesicles with the instant loss
      of color. Therefore, AF-PCDA can be considered to be a novel PDA-based
      colorimetric sensing material with high mechanical strength, which has the
      potential to be employed in various areas involving advanced sensing
      technologies. 

PMID- 25602611
TI  - Lower cell wall pectin solubilisation and galactose loss during early fruit
      development in apple (Malus x domestica) cultivar 'Scifresh' are associated with
      slower softening rate.
AB  - Substantial differences in softening behaviour can exist between fruit even
      within the same species. Apple cultivars 'Royal Gala' and 'Scifresh' soften at
      different rates despite having a similar genetic background and producing similar
      amounts of ethylene during ripening. An examination of cell wall metabolism from
      the fruitlet to the ripe stages showed that in both cultivars pectin
      solubilisation increased during cell expansion, declined at the mature stage and
      then increased again during ripening. This process was much less pronounced in
      the slower softening 'Scifresh' than in 'Royal Gala' at every developmental stage
      examined, consistent with less cell separation and softening in this cultivar.
      Both cultivars also exhibited a progressive loss of pectic galactan and arabinan
      side chains during development. The cell wall content of arabinose residues was
      similar in both cultivars, but the galactose residue content in 'Scifresh'
      remained higher than that of 'Royal Gala' at every developmental stage. The
      higher content of cell wall galactose residue in 'Scifresh' cell walls correlated
      with a lower beta-galactosidase activity and more intense immunolabelling of RG-I
      galactan side chains in both microscopy sections and glycan microarrays. A high
      cell wall galactan content has been associated with reduced cell wall porosity,
      which may restrict access of cell wall-modifying enzymes and thus maintain better
      structural integrity later in development. The data suggest that the composition
      and structure of the cell wall at very early development stages may influence
      subsequent cell wall loosening, and may even predispose the wall's ensuing
      properties. 

PMID- 25602614
TI  - Why does Asn71 deamidate faster than Asn15 in the enzyme triosephosphate
      isomerase? Answers from microsecond molecular dynamics simulation and QM/MM free
      energy calculations.
AB  - Deamidation is the uncatalyzed process by which asparagine or glutamine can be
      transformed into aspartic acid or glutamic acid, respectively. In its active
      homodimeric form, mammalian triosephosphate isomerase (TPI) contains two
      deamidation sites per monomer. Experimental evidence shows that the primary
      deamidation site (Asn71-Gly72) deamidates faster than the secondary deamidation
      site (Asn15-Gly16). To evaluate the factors controlling the rates of these two
      deamidation sites in TPI, we have performed graphics processing unit-enabled
      microsecond long molecular dynamics simulations of rabbit TPI. The kinetics of
      asparagine dipeptide and two deamidation sites in mammalian TPI are also
      investigated using quantum mechanical/molecular mechanical tools with the
      umbrella sampling technique. Analysis of the simulations has been performed using
      independent global and local descriptors that can influence the deamidation
      rates: desolvation effects, backbone acidity, and side chain conformations. Our
      findings show that all the descriptors add up to favor the primary deamidation
      site over the secondary one in mammalian TPI: Asn71 deamidates faster because it
      is more solvent accessible, the adjacent glycine NH backbone acidity is enhanced,
      and the Asn side chain has a preferential near attack conformation. The crucial
      impact of the backbone amide acidity of the adjacent glycine on the deamidation
      rate is shown by kinetic analysis. Our findings also shed light on the effect of
      high-order structure on deamidation: the deamidation in a small peptide is
      favored first because of the higher reactivity of the asparagine residue and then
      because of the stronger stability of the tetrahedral intermediate. 

PMID- 25602615
TI  - The Health Literacy and ESL study: a community-based intervention for Spanish
      speaking adults.
AB  - Although Hispanics have a documented high risk of limited health literacy, there
      is a scarcity of research with this population group, and particularly with
      Hispanic immigrants who generally confront language barriers that have been
      related to low health literacy. The National Action Plan to Improve Health
      Literacy identified community-based English-language instruction as a strategy
      that can facilitate a health literate society. However, the literature lacks
      discussion on this type of intervention. This randomized control trial aimed to
      test the feasibility of using conventional English-as-a-second-language (ESL)
      instruction for improving health literacy among Spanish-speaking adults.
      Objectives included the development, implementation, and evaluation of a health
      literacy/ESL curriculum. The Test of Functional Health Literacy in Adults
      (TOFHLA) in English was used to assess health literacy levels. Analyses included
      independent sample t test, chi-square, and multiple linear regression. A total of
      155 people participated. Results showed a significantly higher increase in the
      TOFHLA posttest score in the intervention group (p = .01), and noticeable
      differences in health literacy levels between groups. Results indicate that ESL
      constitutes a promising venue for improving health literacy among Spanish
      speaking adults. Incorporating health literacy-related content may provide
      additional benefits. 

PMID- 25602616
TI  - Geographic wormhole detection in wireless sensor networks.
AB  - Wireless sensor networks (WSNs) are ubiquitous and pervasive, and therefore;
      highly susceptible to a number of security attacks. Denial of Service (DoS)
      attack is considered the most dominant and a major threat to WSNs. Moreover, the
      wormhole attack represents one of the potential forms of the Denial of Service
      (DoS) attack. Besides, crafting the wormhole attack is comparatively simple;
      though, its detection is nontrivial. On the contrary, the extant wormhole defense
      methods need both specialized hardware and strong assumptions to defend against
      static and dynamic wormhole attack. The ensuing paper introduces a novel scheme
      to detect wormhole attacks in a geographic routing protocol (DWGRP). The main
      contribution of this paper is to detect malicious nodes and select the best and
      the most reliable neighbors based on pairwise key pre-distribution technique and
      the beacon packet. Moreover, this novel technique is not subject to any specific
      assumption, requirement, or specialized hardware, such as a precise synchronized
      clock. The proposed detection method is validated by comparisons with several
      related techniques in the literature, such as Received Signal Strength (RSS),
      Authentication of Nodes Scheme (ANS), Wormhole Detection uses Hound Packet
      (WHOP), and Wormhole Detection with Neighborhood Information (WDI) using the NS-2
      simulator. The analysis of the simulations shows promising results with low False
      Detection Rate (FDR) in the geographic routing protocols. 

PMID- 25602618
TI  - Inferring the distribution and demography of an invasive species from sighting
      data: the red fox incursion into Tasmania.
AB  - A recent study has inferred that the red fox (Vulpes vulpes) is now widespread in
      Tasmania as of 2010, based on the extraction of fox DNA from predator scats.
      Heuristically, this inference appears at first glance to be at odds with the lack
      of recent confirmed discoveries of either road-killed foxes--the last of which
      occurred in 2006, or hunter killed foxes--the most recent in 2001. This paper
      demonstrates a method to codify this heuristic analysis and produce inferences
      consistent with assumptions and data. It does this by formalising the analysis in
      a transparent and repeatable manner to make inference on the past, present and
      future distribution of an invasive species. It utilizes Approximate Bayesian
      Computation to make inferences. Importantly, the method is able to inform
      management of invasive species within realistic time frames, and can be applied
      widely. We illustrate the technique using the Tasmanian fox data. Based on the
      pattern of carcass discoveries of foxes in Tasmania, we infer that the population
      of foxes in Tasmania is most likely extinct, or restricted in distribution and
      demographically weak as of 2013. It is possible, though unlikely, that that
      population is widespread and/or demographically robust. This inference is largely
      at odds with the inference from the predator scat survey data. Our results
      suggest the chances of successfully eradicating the introduced red fox population
      in Tasmania may be significantly higher than previously thought.

PMID- 25602619
TI  - The bias and signal attenuation present in conventional pollen-based climate
      reconstructions as assessed by early climate data from Minnesota, USA.
AB  - The inference of past temperatures from a sedimentary pollen record depends upon
      the stationarity of the pollen-climate relationship. However, humans have altered
      vegetation independent of changes to climate, and consequently modern pollen
      deposition is a product of landscape disturbance and climate, which is different
      from the dominance of climate-derived processes in the past. This problem could
      cause serious signal distortion in pollen-based reconstructions. In the north
      central United States, direct human impacts have strongly altered the modern
      vegetation and hence the pollen rain since Euro-American settlement in the mid
      19th century. Using instrumental temperature data from the early 1800 s from Fort
      Snelling (Minnesota), we assessed the signal distortion and bias introduced by
      using the conventional method of inferring temperature from pollen assemblages in
      comparison to a calibration set from pre-settlement pollen assemblages and the
      earliest instrumental climate data. The early post-settlement calibration set
      provides more accurate reconstructions of the 19th century instrumental record,
      with less bias, than the modern set does. When both modern and pre-industrial
      calibration sets are used to reconstruct past temperatures since AD 1116 from
      pollen counts from a varve-dated record from Lake Mina, Minnesota, the
      conventional inference method produces significant low-frequency (centennial
      scale) signal attenuation and positive bias of 0.8-1.7  degrees C, resulting in
      an overestimation of Little Ice Age temperature and likely an underestimation of
      the extent and rate of anthropogenic warming in this region. However, high
      frequency (annual-scale) signal attenuation exists with both methods. Hence, we
      conclude that any past pollen spectra from before Euro-American settlement in
      this region should be interpreted using a pre-Euro-American settlement pollen
      set, paired to the earliest instrumental climate records. It remains to be
      explored how widespread this problem is when conventional pollen-based inference
      methods are used, and consequently how seriously regional manifestations of
      global warming have been underestimated with traditional pollen-based techniques.

PMID- 25602620
TI  - Structural basis of cofactor-mediated stabilization and substrate recognition of
      the alpha-tubulin acetyltransferase alphaTAT1.
AB  - The functions of microtubules are controlled in part by tubulin post
      translational modification including acetylation of Lys40 in alpha-tubulin.
      alphaTAT1 (alpha-tubulin acetyltransferase 1), an enzyme evolutionarily conserved
      among eukaryotes, has recently been identified as the major alpha-tubulin Lys40
      acetyltransferase, in which AcCoA (acetyl-CoA) serves as an acetyl group donor.
      The regulation and substrate recognition of this enzyme, however, have not been
      fully understood. In the present study, we show that AcCoA and CoA each form a
      stable complex with human alphaTAT1 to maintain the protein integrity both in
      vivo and in vitro. The invariant residues Arg132 and Ser160 in alphaTAT1
      participate in the stable interaction not only with AcCoA but also with CoA,
      which is supported by analysis of the present crystal structures of the alphaTAT1
      catalytic domain in complex with CoA. Alanine substitution for Arg132 or Ser160
      leads to a drastic misfolding of the isolated alphaTAT1 catalytic domain in the
      absence of CoA and AcCoA but not in the presence of excess amounts of either
      cofactor. A mutant alphaTAT1 carrying the R132A or S160A substitution is degraded
      much faster than the wild-type protein when expressed in mammalian Madin-Darby
      canine kidney cells. Furthermore, alanine-scanning experiments using Lys40
      containing peptides reveal that alpha-tubulin Ser38 is crucial for substrate
      recognition of alphaTAT1, whereas Asp39, Ile42, the glycine stretch (amino acid
      residues 43-45) and Asp46 are also involved. The requirement for substrate
      selection is totally different from that in various histone acetyltransferases,
      which appears to be consistent with the inability of alphaTAT1 to acetylate
      histones.

PMID- 25602617
TI  - Molecular epidemiology and phylogenetic analyses of influenza B virus in Thailand
      during 2010 to 2014.
AB  - Influenza B virus remains a major contributor to the seasonal influenza outbreak
      and its prevalence has increased worldwide. We investigated the epidemiology and
      analyzed the full genome sequences of influenza B virus strains in Thailand
      between 2010 and 2014. Samples from the upper respiratory tract were collected
      from patients diagnosed with influenza like-illness. All samples were screened
      for influenza A/B viruses by one-step multiplex real-time RT-PCR. The whole
      genome of 53 influenza B isolates were amplified, sequenced, and analyzed. From
      14,418 respiratory samples collected during 2010 to 2014, a total of 3,050 tested
      positive for influenza virus. Approximately 3.27% (471/14,418) were influenza B
      virus samples. Fifty three isolates of influenza B virus were randomly chosen for
      detailed whole genome analysis. Phylogenetic analysis of the HA gene showed
      clusters in Victoria clades 1A, 1B, 3, 5 and Yamagata clades 2 and 3. Both
      B/Victoria and B/Yamagata lineages were found to co-circulate during this time.
      The NA sequences of all isolates belonged to lineage II and consisted of viruses
      from both HA Victoria and Yamagata lineages, reflecting possible reassortment of
      the HA and NA genes. No significant changes were seen in the NA protein. The
      phylogenetic trees generated through the analysis of the PB1 and PB2 genes
      closely resembled that of the HA gene, while trees generated from the analysis of
      the PA, NP, and M genes showed similar topology. The NS gene exhibited the
      pattern of genetic reassortment distinct from those of the PA, NP or M genes.
      Thus, antigenic drift and genetic reassortment among the influenza B virus
      strains were observed in the isolates examined. Our findings indicate that the co
      circulation of two distinct lineages of influenza B viruses and the limitation of
      cross-protection of the current vaccine formulation provide support for
      quadrivalent influenza vaccine in this region. 

PMID- 25602621
TI  - An iodide-based Li7P2S8I superionic conductor.
AB  - In an example of stability from instability, a Li(7)P(2)S(8)I solid-state Li-ion
      conductor derived from beta-Li(3)PS(4) and LiI demonstrates electrochemical
      stability up to 10 V vs Li/Li(+). The oxidation instability of I is subverted via
      its incorporation into the coordinated structure. The inclusion of I also creates
      stability with the metallic Li anode while simultaneously enhancing the
      interfacial kinetics and ionic conductivity. Low-temperature membrane
      processability enables facile fabrication of dense membranes, making this
      conductor suitable for industrial adoption.

PMID- 25602622
TI  - Shared Brain Connectivity Issues, Symptoms, and Comorbidities in Autism Spectrum
      Disorder, Attention Deficit/Hyperactivity Disorder, and Tourette Syndrome.
AB  - The prevalence of neurodevelopmental disorders, including autism spectrum
      disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and Tourette
      syndrome (TS), has increased over the past two decades. Currently, about one in
      six children in the United States is diagnosed as having a neurodevelopmental
      disorder. Evidence suggests that ASD, ADHD, and TS have similar neuropathology,
      which includes long-range underconnectivity and short-range overconnectivity.
      They also share similar symptomatology with considerable overlap in their core
      and associated symptoms and a frequent overlap in their comorbid conditions.
      Consequently, it is apparent that ASD, ADHD, and TS diagnoses belong to a broader
      spectrum of neurodevelopmental illness. Biologically, long-range
      underconnectivity and short-range overconnectivity are plausibly related to
      neuronal insult (e.g., neurotoxicity, neuroinflammation, excitotoxicity,
      sustained microglial activation, proinflammatory cytokines, toxic exposure, and
      oxidative stress). Therefore, these disorders may a share a similar etiology. The
      main purpose of this review is to critically examine the evidence that ASD, ADHD,
      and TS belong to a broader spectrum of neurodevelopmental illness, an abnormal
      connectivity spectrum disorder, which results from neural long-range
      underconnectivity and short-range overconnectivity. The review also discusses the
      possible reasons for these neuropathological connectivity findings. In addition,
      this review examines the role and issue of axonal injury and regeneration in
      order to better understand the neuropathophysiological interplay between short-
      and long-range axons in connectivity issues. 

PMID- 25602623
TI  - The Effects of Flumazenil After Midazolam Sedation on Cerebral Blood Flow and
      Dynamic Cerebral Autoregulation in Healthy Young Males.
AB  - BACKGROUND: It is unknown whether flumazenil antagonizes the decrease in cerebral
      blood flow or the alteration in dynamic cerebral autoregulation induced by
      midazolam. We, therefore, investigated the effects on cerebral circulation of
      flumazenil administered after midazolam, to test our hypothesis that, along with
      complete reversal of sedation, flumazenil antagonizes the alterations in cerebral
      circulation induced by midazolam. METHODS: Sixteen healthy young male subjects
      received midazolam followed by flumazenil. The modified Observer's Assessment of
      Alertness/Sedation (OAA/S) scale and bispectral index (BIS) were used to assess
      levels of sedation/awareness. For evaluation of cerebral circulation, steady
      state mean cerebral blood flow velocity (MCBFV) was measured by transcranial
      Doppler ultrasonography. In addition, dynamic cerebral autoregulation was
      assessed by spectral and transfer function analysis between mean arterial
      pressure (MAP) variability and MCBFV variability. RESULTS: During midazolam
      sedation, defined by an OAA/S score of 3 (responds only after name is called
      loudly and/or repeatedly), BIS, steady-state MAP, steady-state CBFV, and transfer
      function gain decreased significantly compared with baseline. After flumazenil
      administration, an OAA/S score of 5 (responds readily to name spoken in a normal
      tone) was confirmed. Then, BIS and MAP returned to the same level as baseline.
      However, steady-state MCBFV showed a further significant decrease compared with
      that under midazolam sedation, and the decreased transfer function gain
      persisted. CONCLUSIONS: Contrary to our hypothesis, the present results suggest
      that despite complete antagonism of the sedative effects of midazolam, flumazenil
      would not reverse the alterations in cerebral circulation induced by midazolam.

PMID- 25602624
TI  - Beware of Changes in Intracranial Compliance During Cranioplasty.

PMID- 25602625
TI  - Blowing off the Retained CO2 During Spontaneous Respiration in Neurosurgery: A
      Novel Way!

PMID- 25602626
TI  - Trigeminocardiac reflex: the current clinical and physiological knowledge.
AB  - The trigeminocardiac reflex (TCR) is defined as the sudden onset of
      parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric
      hypermotility during stimulation of any of the sensory branches of the trigeminal
      nerve. Clinically, the TCR has been reported in all the surgical procedures in
      which a structure innervated by the trigeminal nerve is involved. Although, there
      is an abundant literature with reports of incidences and risk factors of the TCR;
      the physiological significance and function of this brainstem reflex has not yet
      been fully elucidated. In addition, there are complexities within the TCR that
      requires examination and clarification. There is also a growing need to discuss
      its cellular mechanism and functional consequences. Therefore, the current review
      provides an updated examination of the TCR with a particular focus on the
      mechanisms and diverse nature of the TCR. 

PMID- 25602627
TI  - [Hepatopulmonary hydatidosis: pediatric case report and literature review].
AB  - Hydatidosis is a parasitic zoonosis of the genus Echinococcus that infects
      herbivores and humans in its larvae stage (hydatid). Pediatric hydatidosis
      usually presents with involvement of the lung, in contrast to the adult clinical
      picture. Therefore, hepatopulmonary hydatidosis is an unusual entity in children.
      A clinical case is presented, along with a short review of available literature.
      A thirteen-year-old male child, who lives in Cauquenes, a rural area of Central
      Chile, presents with three months of cough, fever, malaise, and an abdominal
      mass. Imaging reveals multiple cystic images, located mostly in the right lung
      and the liver. The patient is started on albendazole (15 mg/kg/day) and
      transferred to the Pediatric Surgery Unit in Hospital de Talca. He underwent
      thoracotomy and laparotomy for the removal of the hydatid cysts. He recovered
      from surgery and continued his pharmacological treatment. Hydatidosis is a public
      healthcare problem, and a major cause of morbidity and mortality. It can be
      asymptomatic; thus, its diagnosis requires a high level of suspicion.

PMID- 25602628
TI  - In situ surface-enhanced Raman scattering spectroscopy exploring molecular
      changes of drug-treated cancer cell nucleus.
AB  - Investigating the molecular changes of cancer cell nucleus with drugs treatment
      is crucial for the design of new anticancer drugs, the development of novel
      diagnostic strategies, and the advancement of cancer therapy efficiency. In order
      to better understand the action effects of drugs, accurate location and in situ
      acquisition of the molecular information of the cell nuclei are necessary. In
      this work, we report a microspectroscopic technique called dark-field and
      fluorescence coimaging assisted surface-enhanced Raman scattering (SERS)
      spectroscopy, combined with nuclear targeting nanoprobes, to in situ study Soma
      Gastric Cancer (SGC-7901) cell nuclei treated with two model drugs, e.g., DNA
      binder (Hoechst33342) and anticancer drug (doxorubicin, Dox) via spectral
      analysis at the molecular level. Nuclear targeting nanoprobes with an assembly
      structure of thiol-modified polyethylene glycol polymers (PEG) and nuclear
      localizing signal peptides (NLS) around gold nanorods (AuNRs) were prepared to
      achieve the amplified SERS signals of biomolecules in the cell nuclei. With the
      assistance of dark field/fluorescence imaging with simultaneous location, in situ
      SERS spectra in one cell nucleus were measured and analyzed to disclose the
      effects of Hoechst33342 and Dox on main biomolecules in the cell nuclei. The
      experimental results show that this method possesses great potential to
      investigate the targets of new anticancer drugs and the real-time monitoring of
      the dynamic changes of cells caused by exogenous molecules. 

PMID- 25602629
TI  - An integrated approach to universal prevention: Independent and combined effects
      of PBIS and SEL on youths' mental health.
AB  - Mental health among children and adolescents is a growing national concern and
      schools have taken center stage in efforts to prevent problems and promote
      wellness. Although research and policymakers support the integration of mental
      health services into the schools, there is limited agreement on the ways to
      package or combine existing supports to achieve prevention-oriented goals.
      Positive Behavioral Interventions and Supports (PBIS) and Social Emotional
      Learning (SEL) are 2 of the most widely adopted, evidence-based approaches that
      have been advocated to address student mental health. These universal prevention
      approaches, however, stem from different theoretical camps and are often
      advocated and implemented apart from one another. The purpose of this study was
      to examine the independent and combined effects of PBIS and SEL on student mental
      health outcomes. A quasi-randomized control design at the classroom level was
      used to make comparisons across 4 conditions: business-as-usual (BAU), PBIS
      alone, SEL alone, and COMBO condition with regard to their acceptability to
      teachers, integrity of program delivery, and student outcomes. As predicted, the
      COMBO condition produced significantly greater improvements in overall mental
      health and reductions in externalizing behaviors when compared to all other
      conditions. The results also indicated that the PBIS- and SEL-only conditions
      were both able to produce significant improvements in overall mental health
      functioning as compared with the BAU control. The implications of an integrated
      approach for school-based universal prevention and directions for future research
      are discussed.

PMID- 25602631
TI  - Clinical management of proliferative vitreoretinopathy: an update.
AB  - BACKGROUND: Proliferative vitreoretinopathy (PVR) remains the most significant
      obstacle to successful retinal reattachment surgery. Preclinical studies continue
      to add insights into the complex molecular events leading to PVR development,
      helping to identify new targets for potential prophylactic or therapeutic agents.
      This article reviews the recent evidence supporting surgical and medical
      treatments for PVR. METHODS: PUBMED was used for literature search. Clinical
      studies regarding surgical management of PVR from January 1, 2000 to August 1,
      2014 were included. Clinical studies regarding medical management of PVR from
      January 1, 2000 to August 1, 2014 were included if the design of study was a
      randomized controlled trial. RESULTS: Many recent studies have evaluated surgical
      and medical strategies for the treatment and prevention of PVR. Newer
      vitreoretinal surgery technology (23- and 25-gauge vitrectomy) and tamponade
      agents (heavy silicone oils) have been studied. Medical therapies evaluated
      include antiinflammatory agents, low molecular weight heparin, 5-fluorouracil, 13
      cis-retinoic acid, and daunorubicin, amongst others. CONCLUSION: Surgical
      management with pars plana vitrectomy, with or without scleral buckle or inferior
      retinectomy, remains an effective treatment for PVR-related detachments.
      Consensus regarding a preferred surgical strategy remains controversial. Many
      medical therapies have been studied but fail to demonstrate a statistically
      significant benefit in clinical trials. Further studies to clarify the efficacy
      of available and novel treatment options are warranted.

PMID- 25602630
TI  - PRP4K is a HER2-regulated modifier of taxane sensitivity.
AB  - The taxanes are used alone or in combination with anthracyclines or platinum
      drugs to treat breast and ovarian cancer, respectively. Taxanes target
      microtubules in cancer cells and modifiers of taxane sensitivity have been
      identified in vitro, including drug efflux and mitotic checkpoint proteins. Human
      epidermal growth factor receptor 2 (HER2/ERBB2) gene amplification is associated
      with benefit from taxane therapy in breast cancer yet high HER2 expression also
      correlates with poor survival in both breast and ovarian cancer. The pre-mRNA
      splicing factor 4 kinase PRP4K (PRPF4B), which we identified as a component of
      the U5 snRNP also plays a role in regulating the spindle assembly checkpoint
      (SAC) in response to microtubule-targeting drugs. In this study, we found a
      positive correlation between PRP4K expression and HER2 status in breast and
      ovarian cancer patient tumors, which we determined was a direct result of PRP4K
      regulation by HER2 signaling. Knock-down of PRP4K expression reduced the
      sensitivity of breast and ovarian cancer cell lines to taxanes, and low PRP4K
      levels correlated with in vitro-derived and patient acquired taxane resistance in
      breast and ovarian cancer. Patients with high-grade serous ovarian cancer and
      high HER2 levels had poor overall survival; however, better survival in the low
      HER2 patient subgroup treated with platinum/taxane-based therapy correlated
      positively with PRP4K expression (HR = 0.37 [95% CI 0.15-0.88]; p = 0.03). Thus,
      PRP4K functions as a HER2-regulated modifier of taxane sensitivity that may have
      prognostic value as a marker of better overall survival in taxane-treated ovarian
      cancer patients. 

PMID- 25602632
TI  - Optical coherence tomography-based positioning regimen for macular hole surgery.
AB  - PURPOSE: To evaluate an optical coherence tomography (OCT)-based positioning
      regimen for patients undergoing macular hole surgery. METHOD: We reviewed the
      medical records of all patients in our practice who underwent macular hole
      repair, instituting a modified OCT-based positioning regimen from November 1,
      2011 through July 31, 2013. The regimen consisted of prone positioning at the
      conclusion of surgery with daily OCT imaging until the hole was confirmed closed
      at which point positioning was halted. Clinical data that were collected and
      recorded included visual acuities, stage of hole, size of hole, chronicity,
      preoperative and postoperative OCT imaging, and length of follow-up. RESULTS: We
      identified 33 patients (35 eyes) with a mean baseline visual acuity of 20/220, a
      mean hole size of 465 MUm. The mean final (postoperative) visual acuity was
      20/135 with a mean follow-up of 7.7 months. Six patients (17%) in our study were
      diagnosed with myopic degeneration. Thirteen patients (37%) were found to have
      chronic (>=12 months) holes, and 19 (54%) were found to have large holes (>400
      MUm). Overall, 28 eyes (80%) had persistent closure of macular holes with an OCT
      based positioning regimen. In the absence of high risk factors, such as myopic
      degeneration, chronic or large holes, the closure rate was 92%. In the presence
      of 2 or 3 of these risk factors, the closure rate was 85% and 74%, respectively.
      CONCLUSION: The presence of 2 or 3 high risk factors, such as myopic
      degeneration, chronic holes (>=12 months), or large holes (>400 MUm) can
      compromise outcomes resulting in reopening after apparent early closure. Based on
      the presence of these risk factors, a modified postoperative positioning regimen
      can be used to obtain complete and persistent closure.

PMID- 25602633
TI  - AIR VERSUS GAS TAMPONADE IN RHEGMATOGENOUS RETINAL DETACHMENT WITH INFERIOR
      BREAKS AFTER 23-GAUGE PARS PLANA VITRECTOMY: A Prospective, Randomized
      Comparative Interventional Study.
AB  - PURPOSE: To compare the efficacy of air and octafluoropropane (C3F8) in treating
      rhegmatogenous retinal detachments with inferior breaks after 23-gauge pars plana
      vitrectomy. METHODS: A prospective, randomized comparative interventional study.
      Sixty-four patients with rhegmatogenous retinal detachment with inferior breaks
      underwent pars plana vitrectomy with air (32 eyes) or gas (32 eyes) tamponade.
      Anatomical and visual outcomes of the two groups were compared. RESULTS: The mean
      follow-up period was 13.09 +/- 1.90 months. Significant differences were
      identified regarding prone positioning period (P < 0.01), intraocular pressure (P
      < 0.01), and gas volume (P = 0.03) on the first postoperative day. The single
      operation success rates for the air and gas groups were 84.38% and 78.13% (P =
      0.522), and the final surgery success rates increased to 100% and 96.88% (P =
      0.313), respectively. The single-operation success rate between the groups was
      not statistically significant, even after adjustment for confounding factors.
      Multivariate logistic regression also indicated that the number of involved
      retinal quadrants (odds ratio = 19.88, P = 0.01) was an independent predictor of
      surgery failure. The only postoperative complication observed was new or missed
      breaks, which occurred in 12 patients (18.75%). CONCLUSION: Air had equivalent
      tamponade effects to C3F8, with a shorter prone positioning period, fewer
      complications, and less expense, in the surgical management of rhegmatogenous
      retinal detachment with inferior breaks.

PMID- 25602636
TI  - Exploring Skills-Based Competencies Through Geriatric Care Management Modules.
AB  - As educational competencies in gerontology continue to evolve, skills-based
      competencies (from beginner to expert level) endure as the hallmarks of the
      field. This study explored the impact of exposure to "active learning" modules
      for the practice of professional geriatric care management (GCM) on beginning
      gerontology students and their ability to acquire core knowledge and more
      advanced skills related to assessment and counseling community-based older
      adults. Working with a group of "nontraditional" students, many having previous
      caregiving experience and working with older adults in direct care and allied
      health care roles, evaluation of these modules show that early exposure to
      "advanced" professional practice can be an effective approach for introducing
      higher-level competencies to beginning gerontology students.

PMID- 25602635
TI  - Measurement of the membrane dipole electric field in DMPC vesicles using
      vibrational shifts of p-cyanophenylalanine and molecular dynamics simulations.
AB  - The magnitude of the membrane dipole field was measured using vibrational Stark
      effect (VSE) shifts of nitrile oscillators placed on the unnatural amino acid p
      cyanophenylalanine (p-CN-Phe) added to a peptide sequence at four unique
      positions. These peptides, which were based on a repeating alanine-leucine motif,
      intercalated into small unilamellar DMPC vesicles which formed an alpha-helix as
      confirmed by circular dichroic (CD) spectroscopy. Molecular dynamics simulations
      of the membrane-intercalated helix containing two of the nitrile probes, one near
      the headgroup region of the lipid (alphaLAX(25)) and one buried in the interior
      of the bilayer (alphaLAX(16)), were used to examine the structure of the nitrile
      with respect to the membrane normal, the assumed direction of the dipole field,
      by quantifying both a small tilt of the helix in the bilayer and conformational
      rotation of the p-CN-Phe side chain at steady state. Vibrational absorption
      energies of the nitrile oscillator at each position showed a systematic blue
      shift as the nitrile was stepped toward the membrane interior; for several
      different concentrations of peptide, the absorption energy of the nitrile located
      in the middle of the bilayer was ~3 cm(-1) greater than that of the nitrile
      closest to the surface of the membrane. Taken together, the measured VSE shifts
      and nitrile orientations within the membrane resulted in an absolute magnitude of
      8-11 MV/cm for the dipole field, at the high end of the range of possible values
      that have been accumulated from a variety of indirect measurements. Implications
      for this are discussed. 

PMID- 25602638
TI  - Introduction to papers published from the AIRMON symposium, Marseille, France, 15
      19 June 2014.

PMID- 25602639
TI  - Cobalt-catalyzed C-H cyanation of (hetero)arenes and 6-arylpurines with N
      cyanosuccinimide as a new cyanating agent.
AB  - A cobalt-catalyzed C-H cyanation reaction of arenes has been developed using N
      cyanosuccinimide as a new electrophilic cyanating agent. The reaction proceeds
      with high selectivity to afford monocyanated products with excellent functional
      group tolerance. Substrate scope was found to be broad enough to include a wide
      range of heterocycles including 6-arylpurines. 

PMID- 25602640
TI  - Fabrication of spinel one-dimensional architectures by single-spinneret
      electrospinning for energy storage applications.
AB  - A facile and general method is developed to fabricate one-dimensional (1D) spinel
      composite oxides with complex architectures by using a facile single-spinneret
      electrospinning technique. It is found that precursor polymers and heating rates
      could control the structures of the products, such as 1D solid, nanotube and tube
      in-tubes structures. Especially, the tube-in-tube structures have been
      successfully fabricated for various mixed metal oxide, including CoMn2O4,
      NiCo2O4, CoFe2O4, NiMn2O4 and ZnMn2O4. Benefiting from the unique structure
      features, the tube-in-tube hollow nanostructures possess superior electrochemical
      performances in asymmetric supercapacitors and Li-O2 batteries. 

PMID- 25602637
TI  - Novel 5-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of glycinamide
      ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide
      ribonucleotide formyltransferase and as potential antitumor agents.
AB  - A new series of 5-substituted thiopheneyl pyrrolo[2,3-d]pyrimidines 6-11 with
      varying chain lengths (n = 1-6) were designed and synthesized as hybrids of the
      clinically used anticancer drug pemetrexed (PMX) and our 6-substituted
      thiopheneyl pyrrolo[2,3-d]pyrimidines 2c and 2d with folate receptor (FR) alpha
      and proton-coupled folate transporter (PCFT) uptake specificity over the reduced
      folate carrier (RFC) and inhibition of de novo purine nucleotide biosynthesis at
      glycinamide ribonucleotide formyltransferase (GARFTase). Compounds 6-11 inhibited
      KB human tumor cells in the order 9 = 10 > 8 > 7 > 6 = 11. Compounds 8-10 were
      variously transported by FRalpha, PCFT, and RFC and, unlike PMX, inhibited de
      novo purine nucleotide rather than thymidylate biosynthesis. The
      antiproliferative effects of 8 and 9 appeared to be due to their dual inhibitions
      of both GARFTase and 5-aminoimidazole-4-carboxamide ribonucleotide
      formyltransferase. Our studies identify a unique structure-activity relationship
      for transport and dual target inhibition. 

PMID- 25602642
TI  - Isotopic and elemental profiling of ammonium nitrate in forensic explosives
      investigations.
AB  - Ammonium nitrate (AN) is frequently encountered in explosives in forensic
      casework. It is widely available as fertilizer and easy to implement in explosive
      devices, for example by mixing it with a fuel. Forensic profiling methods to
      determine whether material found on a crime scene and material retrieved from a
      suspect arise from the same source are becoming increasingly important. In this
      work, we have explored the possibility of using isotopic and elemental profiling
      to discriminate between different batches of AN. Variations within a production
      batch, between different batches from the same manufacturer, and between batches
      from different manufacturers were studied using a total of 103 samples from 19
      different fertilizer manufacturers. Isotope-ratio mass spectrometry (IRMS) was
      used to analyze AN samples for their (15)N and (18)O isotopic composition. The
      trace-elemental composition of these samples was studied using inductively
      coupled plasma-mass spectrometry (ICP-MS). All samples were analyzed for the
      occurrence of 66 elements. 32 of these elements were useful for the
      differentiation of AN samples. These include magnesium (Mg), calcium (Ca), iron
      (Fe) and strontium (Sr). Samples with a similar elemental profile may be
      differentiated based on their isotopic composition. Linear discriminant analysis
      (LDA) was used to calculate likelihood ratios and demonstrated the power of
      combining elemental and isotopic profiling for discrimination between different
      sources of AN. 

PMID- 25602643
TI  - Novel shortcut estimation method for regeneration energy of amine solvents in an
      absorption-based carbon capture process.
AB  - Among various CO2 capture processes, the aqueous amine-based absorption process
      is considered the most promising for near-term deployment. However, the
      performance evaluation of newly developed solvents still requires complex and
      time-consuming procedures, such as pilot plant tests or the development of a
      rigorous simulator. Absence of accurate and simple calculation methods for the
      energy performance at an early stage of process development has lengthened and
      increased expense of the development of economically feasible CO2 capture
      processes. In this paper, a novel but simple method to reliably calculate the
      regeneration energy in a standard amine-based carbon capture process is proposed.
      Careful examination of stripper behaviors and exploitation of energy balance
      equations around the stripper allowed for calculation of the regeneration energy
      using only vapor-liquid equilibrium and caloric data. Reliability of the proposed
      method was confirmed by comparing to rigorous simulations for two well-known
      solvents, monoethanolamine (MEA) and piperazine (PZ). The proposed method can
      predict the regeneration energy at various operating conditions with greater
      simplicity, greater speed, and higher accuracy than those proposed in previous
      studies. This enables faster and more precise screening of various solvents and
      faster optimization of process variables and can eventually accelerate the
      development of economically deployable CO2 capture processes. 

PMID- 25602641
TI  - Right ventricle-pulmonary circulation dysfunction: a review of energy-based
      approach.
AB  - Patients with repaired or palliated right heart congenital heart disease (CHD)
      are often left with residual lesions that progress and can result in significant
      morbidity. However, right ventricular-pulmonary arterial evaluation and the
      timing of reintvervention is still subjective. Currently, it relies on
      symptomology, or RV imaging-based metrics from echocardiography or MR derived
      parameters including right ventricular (RV) ejection fraction (EF), end-systolic
      pressure (ESP), and end-diastolic volume (EDV). However, the RV is coupled to the
      pulmonary vasculature, and they are not typically evaluated together. For
      example, the dysfunctional right ventricular-pulmonary circulation (RV-PC)
      adversely affects the RV myocardial performance resulting in decreased
      efficiency. Therefore, comprehensive hemodynamic assessment should incorporate
      changes in RV-PC and energy efficiency for CHD patients. The ventricular pressure
      volume relationship (PVR) and other energy-based endpoints derived from PVR, such
      as stroke work (SW) and ventricular elastance (Ees), can provide a measure of RV
      performance. However, a detailed explanation of the relationship between RV
      performance and pulmonary arterial hemodynamics is lacking. More importantly, PVR
      is impractical for routine longitudinal evaluation in a clinical setting, because
      it requires invasive catheterization. As an alternative, analytical methods and
      computational fluid dynamics (CFD) have been used to compute energy endpoints,
      such as power loss or energy dissipation, in abnormal physiologies. In this
      review, we review the causes of RV-PA failure and the limitation of current
      clinical parameters to quantify RV-PC dysfunction. Then, we describe the
      advantage of currently available energy-based endpoints and emerging energy
      endpoints, such as energy loss in the Pas or kinetic energy, obtained from a new
      non-invasive imaging technique, i.e. 4D phase contrast MRI.

PMID- 25602644
TI  - Modeling microorganism transport and survival in the subsurface.
AB  - An understanding of microbial transport and survival in the subsurface is needed
      for public health, environmental applications, and industrial processes. Much
      research has therefore been directed to quantify mechanisms influencing microbial
      fate, and the results demonstrate a complex coupling among many physical,
      chemical, and biological factors. Mathematical models can be used to help
      understand and predict the complexities of microbial transport and survival in
      the subsurface under given assumptions and conditions. This review highlights
      existing model formulations that can be used for this purpose. In particular, we
      discuss models based on the advection-dispersion equation, with terms for kinetic
      retention to solid-water and/or air-water interfaces; blocking and ripening;
      release that is dependent on the resident time, diffusion, and transients in
      solution chemistry, water velocity, and water saturation; and microbial decay
      (first-order and Weibull) and growth (logistic and Monod) that is dependent on
      temperature, nutrient concentration, and/or microbial concentration. We highlight
      a two-region model to account for microbe migration in the vicinity of a solid
      phase and use it to simulate the coupled transport and survival of species under
      a variety of environmentally relevant scenarios. This review identifies
      challenges and limitations of models to describe and predict microbial transport
      and survival. In particular, many model parameters have to be optimized to
      simulate a diversity of observed transport, retention, and survival behavior at
      the laboratory scale. Improved theory and models are needed to predict the fate
      of microorganisms in natural subsurface systems that are highly dynamic and
      heterogeneous. 

PMID- 25602646
TI  - Effect of hillslope position and manure application rates on the persistence of
      fecal source tracking indicators in an agricultural soil.
AB  - The influence of liquid dairy manure (LDM) application rates (12.5 and 25 kL ha)
      and soil type on the decay rates of library-independent fecal source tracking
      markers (host-associated and mitochondrial DNA) and persistent (>58 d) population
      structure was examined in a field study. The soils compared were an Aquic
      Haplorthod and a Typic Haplorthod in Nova Scotia, Canada, that differed according
      to landscape position and soil moisture regime. Soil type and LDM application
      rate did not influence decay rates (0.045-0.057 d). population structure, in
      terms of the occurrence of abundance of strain types, varied according to soil
      type ( = 0.012) but did not vary by LDM application rate ( = 0.121). Decay of
      ruminant-specific (BacR), bovine-specific (CowM2), and mitochondrial DNA (AcytB)
      markers was analyzed for 13 d after LDM application. The decay rates of BacR were
      greater under high-LDM application rates (0.281-0.358 d) versus low-LDM
      application rates (0.212-0.236 d) but were unaffected by soil type. No decay
      rates could be calculated for the CowM2 marker because it was undetectable within
      6 d after manure application. Decay rates for AcytB were lower for the Aquic
      Haplorthod (0.088-0.100 d), with higher moisture status compared with the Typic
      Haplorthod (0.135 d). Further investigation into the decay of fecal source
      tracking indicators in agricultural field soils is warranted to assess the
      influence of soil type and agronomic practice on the differential decay of
      relevant markers and the likelihood of transport in runoff. 

PMID- 25602645
TI  - Biodegradation of nitroglycerin from propellant residues on military training
      ranges.
AB  - Nitroglycerin (NG) is often present in soils and sometimes in pore water at
      antitank firing positions due to incomplete combustion of propellants. Various
      degradation processes can contribute to the natural attenuation of NG in soils
      and pore water, thus reducing the risks of groundwater contamination. However,
      until now these processes have been sparsely documented. This study aimed at
      evaluating the ability of microorganisms from a legacy firing position to degrade
      dissolved NG, as well as NG trapped within propellant particles. Results from the
      shake-flask experiments showed that the isolated culture is capable of degrading
      dissolved NG but not the nitrocellulose matrix of propellant particles, so that
      the deeply embedded NG molecules cannot be degraded. Furthermore, the results
      from column experiments showed that in a nutrient-poor sand, degradation of
      dissolved NG may not be sufficiently rapid to prevent groundwater contamination.
      Therefore, the results from this study indicate that, under favorable soil
      conditions, biodegradation can be an important natural attenuation process for NG
      dissolving out of fresh propellant residues. In contrast, biodegradation does not
      contribute to the long-term attenuation of NG within old, weathered propellant
      residues. Although NG in these old residues no longer poses a threat to
      groundwater quality, if soil clean-up of a legacy site is required, active
      remediation approaches should be sought. 

PMID- 25602647
TI  - Chloride Dispersion across Silt Deposits in a Glaciated Bedrock River Valley.
AB  - Soil and groundwater from the Neponset River floodplain deposit that receive high
      concentrations of deicing agents from nearby highways were investigated. The
      silty sand floodplain is separated by a silty aquitard from the underlying
      aquifer that serves as a public water supply. We made a transport-based
      assessment of the capacity of the aquitard to protect the underlying aquifer. One
      hundred seventeen soil samples and 469 groundwater samples collected during a
      period of 4 yr from boreholes and 10 wells grouped in two well clusters were
      analyzed for dissolved Cl concentration. The soil characterization and
      groundwater monitoring results agreed, showing a very slow change in subsurface
      Cl contamination with time. These data also calibrated a vertical one-dimensional
      advective-dispersive transport model across the deposits. Advective transport
      dominated only in the top 3.37 m of the floodplain deposit, with dispersion being
      the main transport mechanism below this depth. Due to the silty nature of the
      aquitard, dispersion rather than diffusion was the main transport mechanism into
      the floodplain-aquitard system. Soil and groundwater quality data confirmed a Cl
      concentration at the floodplain surface near the highway runoff drainage outlets
      of 2450 mg L. The model estimated a vertical dispersivity at the site of 8 mm and
      a vertical hydrodynamic dispersion coefficient of 3.71 * 10 m s. These data
      confirmed the aquitard's capacity to contain deicing agents, protecting the
      underlying aquifer from contamination. 

PMID- 25602648
TI  - Immobilization of lead in soil influenced by soluble phosphate and calcium: lead
      speciation evidence.
AB  - We investigated the effect of soluble Ca on the speciation of Pb in phosphate
      amended soils. A calcareous soil was amended in sequence with soluble phosphate
      (0 and 299 mg kg P), calcium nitrate (0, 200, and 400 mg kg Ca), and/or lead
      nitrate (0 and 1000 mg kg Pb) and incubated for 50 d. Extractable Ca was
      relatively similar across all samples, with a minor reduction in Ca release for
      treatments amended with P possibly from the formation of Ca-phosphate minerals.
      Olsen-P extractability from P-added treatments was highest in the non-Pb-amended
      soils and was about 40% lower when Pb was added as a result of Pb-phosphate
      formation. In the absence of P, diethylene triamine pentaacetic acid (DTPA)-Pb
      extractability increased with increasing Ca amendment; however, in the P-amended
      treatments, DTPA-Pb decreased with increasing Ca addition. X-ray absorption
      spectroscopy results of the Pb spiked soils indicate that adsorbed Pb is the
      primary phase (up to 92%) in non-P-amended soils with minor distribution to
      hydrocerussite and Pb-phosphate phases. In the P-amended treatments, Pb
      speciation shifted to Pb-phosphate [chloropyromorphite and Pb(PO)] (42-48%) and
      adsorbed Pb (44-50%). As Ca concentration increased in the P-amended soils, Pb
      phosphate speciation moved from combined chloropyromorphite and Pb(PO) (0 mg kg
      Ca) to exclusively chloropyromorphite. The study demonstrates that soluble Ca
      enhances Pb immobilization with P amendments. 

PMID- 25602649
TI  - Field evaluations on soil plant transfer of lead from an urban garden soil.
AB  - Lead (Pb) is one of the most common contaminants in urban soils. Gardening in
      contaminated soils can result in Pb transfer from soil to humans through
      vegetable consumption and unintentional direct soil ingestion. A field experiment
      was conducted in 2009 and 2010 in a community urban garden with a soil total Pb
      concentration of 60 to 300 mg kg. The objectives of this study were to evaluate
      soil-plant transfer of Pb, the effects of incorporation of a leaf compost as a
      means of reducing Pb concentrations in vegetables and the bioaccessibility of
      soil Pb, and the effects of vegetable cleaning techniques on the Pb
      concentrations in the edible portions of vegetables. The amount of compost added
      was 28 kg m. The tested plants were Swiss chard, tomato, sweet potato, and
      carrots. The vegetable cleaning techniques were kitchen cleaning, laboratory
      cleaning, and peeling. Compost addition diluted soil total Pb concentration by 29
      to 52%. Lead concentrations of the edible portions of vegetables, except carrot,
      were below the maximum allowable limits of Pb established by the Food and
      Agriculture Organization and the World Health Organization. Swiss chard and
      tomatoes subjected to kitchen cleaning had higher Pb concentrations than
      laboratory-cleaned plants. Cleaning methods did not affect Pb concentrations in
      carrots. Bioaccessible Pb in the compost-added soils was 20 to 30% less than that
      of the no-compost soils; compost addition reduced the potential of transferring
      soil Pb to humans via vegetable consumption and direct soil ingestion. Thorough
      cleaning of vegetables further reduced the potential of transferring soil Pb to
      humans. 

PMID- 25602650
TI  - Micro-x-ray fluorescence, micro-x-ray absorption spectroscopy, and micro-x-ray
      diffraction investigation of lead speciation after the addition of different
      phosphorus amendments to a smelter-contaminated soil.
AB  - The stabilization of Pb on additions of P to contaminated soils and mine spoil
      materials has been well documented. It is clear from the literature that
      different P sources result in different efficacies of Pb stabilization in the
      same contaminated material. We hypothesized that the differences in the efficacy
      of Pb stabilization in contaminated soils on fluid or granular P amendment
      addition is due to different P reaction processes in and around fertilizer
      granules and fluid droplets. We used a combination of several synchrotron-based
      techniques (i.e., spatially resolved micro-X-ray fluorescence, micro-X-ray
      absorption near-edge structure spectroscopy, and micro-X-ray diffraction) to
      speciate Pb at two incubation times in a smelter-contaminated soil on addition of
      several fluid and granular P amendments. The results indicated that the Pb
      phosphate mineral plumbogummite was an intermediate phase of pyromorphite
      formation. Additionally, all fluid and granular P sources were able to induce Pb
      phosphate formation, but fluid phosphoric acid (PA) was the most effective with
      time and distance from the treatment. Granular phosphate rock and triple super
      phosphate (TSP) amendments reacted to generate Pb phosphate minerals, with TSP
      being more effective at greater distances from the point of application. As a
      result, PA and TSP were the most effective P amendments at inducing Pb phosphate
      formation, but caution needs to be exercised when adding large amounts of soluble
      P to the environment. 

PMID- 25602651
TI  - Zinc and cadmium adsorption to aluminum oxide nanoparticles affected by naturally
      occurring ligands.
AB  - Nanoparticles of aluminum oxide (AlO) are efficient in removing Cd, Zn, and other
      heavy metals from wastewaters and soil solutions due to their high specific
      surface area and surface area to volume ratio. Naturally occurring ligands, such
      as phosphate (PO), citrate, and humic acid (HA), may affect the efficiency of AlO
      nanoparticles in adsorption of Cd and Zn. The objective of this study was to
      investigate Zn and Cd adsorption to AlO nanoparticles as influenced by PO,
      citrate, and HA. Adsorption of Zn and Cd was performed in mono-metal and binary
      metal systems at pH 6.5 with initial metal concentration of 1.0 mmol L and
      varying ligand concentration at a solid:solution ratio of 1:1000. Adsorption
      isotherms showed that Zn had higher affinity to the AlO nanoparticle surface than
      Cd and that adsorption of Zn and Cd in the binary-metal system was lower than in
      the respective mono-metal systems. Phosphate and HA enhanced Zn and Cd adsorption
      in all systems, whereas citrate reduced Zn adsorption in the mono-metal system by
      25% and increased adsorption in the other metal systems. Removal of Zn or Cd from
      the systems was generally accompanied by enhanced removal of PO and HA, which may
      indicate enhanced adsorption due to ternary complex formation or metal-ligand
      precipitation. Phosphate was the most effective among the three ligands in
      enhancing Zn and Cd adsorption. Overall, AlO nanoparticles are suitably used for
      Zn and Cd adsorption, which can be significantly enhanced by the presence of PO
      or HA and to a lesser degree by citrate at low concentrations. 

PMID- 25602634
TI  - Topical nepafenec in eyes with noncentral diabetic macular edema.
AB  - PURPOSE: To evaluate the effect of a topical, nonsteroidal antiinflammatory drug,
      nepafenac 0.1%, in eyes with noncentral diabetic macular edema. METHODS:
      Multicenter, double-masked randomized trial. Individuals with good visual acuity
      and noncentral-involved diabetic macular edema were randomly assigned to
      nepafenac 0.1% (N = 61) or placebo (nepafenac vehicle, N = 64) 3 times a day for
      12 months. The primary outcome was mean change in optical coherence tomography
      retinal volume at 12 months. RESULTS: Mean baseline retinal volume was 7.8 mm. At
      12 months, in the nepafenac and placebo groups respectively, mean change in
      retinal volume was -0.03 mm and -0.02 mm (treatment group difference: -0.02, 95%
      confidence interval: -0.27 to 0.23, P = 0.89). Central-involved diabetic macular
      edema was present in 7 eyes (11%) and 9 eyes (14%) at the 12-month visit (P =
      0.79), respectively. No differences in visual acuity outcomes were identified.
      One study participant developed a corneal melt after using nepafenac in the
      nonstudy eye, which had a history of severe dry eye. No additional safety
      concerns were evident. CONCLUSION: In eyes with noncentral diabetic macular edema
      and good visual acuity, topical nepafenac 0.1% 3 times daily for 1 year likely
      does not have a meaningful effect on optical coherence tomography-measured
      retinal thickness.

PMID- 25602652
TI  - Chromium-resistant bacteria promote the reduction of hexavalent chromium in
      soils.
AB  - Knowledge of the chromium (Cr) redox process in soil is important in addressing
      Cr bioavailability and risk assessment of contaminated soils. In this study,
      seven representative agricultural soils with different physicochemical properties
      were used to investigate the importance of microbially mediated Cr(VI) reduction
      and the response of soil bacterial community to Cr contamination. Chromium
      application increased soil bacterial diversity in Periudic Argosols, Calcaric
      Regosols, Stagnic Anthrosols, Mollisols, Typic Haplustalfs, and Ustic Cambosols,
      with an exception of Udic Ferrisols. The soil bacterial community responded to Cr
      contamination through changes in bacterial community structure, with Cr-resistant
      bacteria becoming the dominant species, and the percentage of Cr-resistant
      bacteria of total cultivable bacteria was 89.9, 75.2, 92.8, 65.3, 72.8, 77.3, and
      65.4%, respectively, for Periudic Argosols, Udic Ferrisols, Calcaric Regosols,
      Stagnic Anthrosols, Mollisols, Typic Haplustalfs, and Ustic Cambosols. , , , , ,
      , , , , and were identified as the Cr-resistant bacteria. Moreover, our results
      demonstrated that microbial reduction was an important Cr(VI) reduction pathway,
      and the relative contribution of microorganisms to Cr(VI) reduction was 14.4,
      44.0, 20.6, 34.9, 21.9, 21.7, and 22.0%, respectively for Periudic Argosols, Udic
      Ferrisols, Calcaric Regosols, Stagnic Anthrosols, Mollisols, Typic Haplustalfs,
      and Ustic Cambosols. Soil properties, especially Fe(II) and soil particle
      distribution, affected the microbially mediated Cr(VI) reduction. These results
      provide useful information for the bioremediation of Cr-contaminated soils under
      a wide range of environmental conditions. 

PMID- 25602653
TI  - Repeated annual paper mill and alkaline residuals application affects soil metal
      fractions.
AB  - The application of industrial residuals in agriculture may raise concerns about
      soil and crop metal accumulation. A complete study using a fractionation scheme
      would reveal build-up in metal pools occurring after material addition and
      predict the transformation of metals in soil between the different forms and
      potential metal release into the environment. An experimental study was conducted
      from 2000 to 2008 on a loamy soil at Yamachiche, Quebec, Canada, to evaluate the
      effects of repeated annual addition of combined paper mill biosolids when applied
      alone or with several liming by-products on soil Cu, Zn, and Cd fractions. Wet
      paper mill biosolids at 0, 30, 60, or 90 Mg ha and calcitic lime, lime mud, or
      wood ash, each at 3 Mg ha with 30 Mg paper mill biosolids ha, were surface
      applied after seeding. The soils were sampled after 6 (soybean [ (L.) Merr.]) and
      9 [corn ( L.)] crop years and analyzed using the Tessier fractionation procedure.
      Results indicated that biosolids addition increased exchangeable Zn and Cd,
      carbonate-bound Cd, Fe-Mn oxide-bound Zn and Cd, organically bound Cu and Zn, and
      total Zn and Cd fractions but decreased Fe-Mn oxide-bound Cu in the uppermost 30
      cm layer. With liming by-products, there was a shift from exchangeable to
      carbonate-bound forms. Even with very small metals addition, paper mill and
      liming materials increased the mobility of soil Zn and Cd after 9 yr of
      application, and this metal redistribution resulted into higher crop grain
      concentrations. 

PMID- 25602654
TI  - Leaching of from stony soils after effluent application.
AB  - Irrigation of dairy shed effluent (DSE) onto land is an integral part of New
      Zealand's farming practice. The use of inappropriate soils can result in
      contamination of ground waters with microbes and nutrients. A gap in our
      knowledge is the ability of stony soils to safely treat DSE. Replicates of four
      stony soils were collected from the Canterbury region of New Zealand as intact
      soil lysimeters 460 mm in diameter and up to 750 mm deep. The soils had either
      stones to the surface or 300 to 600 mm fines over stones. To determine
      breakthrough characteristics, a pulse of DSE (25 mm depth) spiked with bromide
      (2000 mg L) was applied to the soil cores followed by continuous artificial
      rainfall, for one pore volume, at 5 mm h. Leachate aliquots were analyzed for ,
      bromide, and NH-N. The lysimeters were then subjected to hoof pugging using a
      mechanical hoof, and the leaching characteristics of the soil were determined
      again. breakthrough curves revealed that the potential for to leach through the
      soils was high for Selwyn very stony soil and low for other soils analyzed. After
      pugging, leaching of increased in Mackenzie soil with stones to the surface. For
      most other soil cores, concentrations in soil leachates were low. In soils where
      stones are close to the surface, especially where the soil matrix is sandy, we
      anticipate that shallow groundwater is vulnerable to microbial contamination
      under some land management practices. 

PMID- 25602655
TI  - Quantifying the Contribution of On-Site Wastewater Treatment Systems to Stream
      Discharge Using the SWAT Model.
AB  - In the southeastern United States, on-site wastewater treatment systems (OWTSs)
      are widely used for domestic wastewater treatment. The degree to which OWTSs
      represent consumptive water use has been questioned in Georgia. The goal of this
      study was to estimate the effect of OWTSs on streamflow in a gauged watershed in
      Gwinnett County, Georgia using the Soil and Water Assessment Tool (SWAT)
      watershed-scale model, which includes a new OWTS algorithm. Streamflow was
      modeled with and without the presence of OWTSs. The model was calibrated using
      data from 1 Jan. 2003 to 31 Dec. 2006 and validated from 1 Jan. 2007 to 31 Dec.
      2010 using the auto-calibration tool SWAT-CUP 4. The daily and monthly streamflow
      Nash-Sutcliffe coefficients were 0.49 and 0.71, respectively, for the calibration
      period and 0.37 and 0.68, respectively, for the validation period, indicating a
      satisfactory fit. Analysis of water balance output variables between simulations
      showed a 3.1% increase in total water yield at the watershed scale and a 5.9%
      increase at the subbasin scale for a high-density OWTS area. The percent change
      in water yield between simulations was the greatest in dry years, implying that
      the influence of OWTSs on the water yield is greatest under drought conditions.
      Mean OWTS water use was approximately 5.7% consumptive, contrary to common
      assumptions by water planning agencies in Georgia. Results from this study may be
      used by OWTS users and by watershed planners to understand the influence of OWTSs
      on water quantity within watersheds in this region. 

PMID- 25602656
TI  - Runoff losses of excreted chlortetracycline, sulfamethazine, and tylosin from
      surface-applied and soil-incorporated beef cattle feedlot manure.
AB  - Veterinary antimicrobials in land-applied manure can move to surface waters via
      rain or snowmelt runoff, thus increasing their dispersion in agro-environments.
      This study quantified losses of excreted chlortetracycline, sulfamethazine, and
      tylosin in simulated rain runoff from surface-applied and soil-incorporated beef
      cattle ( L.) feedlot manure (60 Mg ha, wet wt.). Antimicrobial concentrations in
      runoff generally reflected the corresponding concentrations in the manure. Soil
      incorporation of manure reduced the concentrations of chlortetracycline (from 75
      to 12 MUg L for a 1:1 mixture of chlortetracycline and sulfamethazine and from 43
      to 17 MUg L for chlortetracycline alone) and sulfamethazine (from 3.9 to 2.6 MUg
      L) in runoff compared with surface application. However, there was no significant
      effect of manure application method on tylosin concentration (range, 0.02-0.06
      MUg L) in runoff. Mass losses, as a percent of the amount applied, for
      chlortetracycline and sulfamethazine appeared to be independent of their
      respective soil sorption coefficients. Mass losses of chlortetracycline were
      significantly reduced with soil incorporation of manure (from 6.5 to 1.7% when
      applied with sulfamethazine and from 6.5 to 3.5% when applied alone). Mass losses
      of sulfamethazine (4.8%) and tylosin (0.24%) in runoff were not affected by
      manure incorporation. Although our results confirm that cattle-excreted
      veterinary antimicrobials can be removed via surface runoff after field
      application, the magnitudes of chlortetracycline and sulfamethazine losses were
      reduced by soil incorporation of manure immediately after application. 

PMID- 25602657
TI  - Carbon-14-glyphosate behavior in relationship to pedoclimatic conditions and crop
      sequence.
AB  - The recognition of glyphosate [(-phosphonomethyl) glycine] behavioral patterns
      can be readily examined using a pedoclimatic gradient. In the present study,
      glyphosate adsorption-desorption and degradation were examined under different
      scenarios in relationship to soil properties and soil use applications. Three
      sites with varied pedoclimatic conditions and two crop sequences were selected.
      Adsorption-desorption and glyphosate distribution in mineralized, extractable,
      and nonextractable fractions were assessed under laboratory conditions.
      Glyphosate sorption was characterized by isotherms and glyphosate degradation
      using the distribution of C-glyphosate radioactivity among mineralized fractions,
      two extractable fractions (in water, ER1; in NHOH, ER2), and nonextractable
      fractions. Results showed sorption indices (distribution coefficient and
      Freundlich sorption coefficient : 13.4 +/- 0.3-64.1 +/- 0.9 L kg and 16.2-60.6,
      respectively), and hysteresis increased among soil sites associated with
      decreasing soil particle size <2 MUm, soil organic matter, and other soil
      properties associated with soil granulometry. A multiple stepwise regression
      analysis was applied to estimate the relationship between values and soil
      properties. Cation exchange capacity, water field capacity, and Bray-1 P were the
      soil properties retained in the equation. Soils under continuous soybean [ (L.)
      Merr.] (monoculture) treatment exhibited reduced glyphosate adsorption and
      decreased hysteresis desorption relative to soils under rotation. To our
      knowledge, these results are the first to demonstrate that soils with identical
      properties exhibited different glyphosate retention capacities based on crop
      sequence. We propose possible explanations for this observation. Our results
      suggested that characterization of the variability in soil property gradients can
      serve to determine glyphosate behavioral patterns, which can establish a
      criterion for use in reducing potential environmental risks. 

PMID- 25602658
TI  - Estimating estrogen release and load from humans and livestock in shanghai,
      china.
AB  - The estrogens estrone (E1), 17beta-estradiol (E2), and 17alpha-ethynylestradiol
      (EE2) cause potent endocrine disruptive effects on aquatic wildlife. Currently,
      four sources of released estrogens exist in Shanghai: treated effluent from
      municipal wastewater treatment plants (WTPs); wastewater discharge from livestock
      farms; untreated or simply digested sewage from rural households; and runoff from
      farmland with livestock manure (LM) applied and irrigated with livestock
      wastewater (LW). A modified estimation method for estrogen release, in
      consideration of the difference in estrogen excretion rates between Caucasian and
      Oriental people and estrogen reduction in livestock wastes, was presented in the
      study. Based on the estimation method, we estimated the amount of estrogen
      release from humans and livestock and analyzed the spatially explicit
      distribution of estrogen loads. By comparing the four estrogen sources, the
      amount of estrogens released to water environments from livestock (56.8 g d), in
      terms of E2 equivalents (EEQ), was nearly twofold higher than the EEQ from humans
      (35.2 g d), which accounted for 61.0% of the total EEQ in Shanghai. Regarding the
      livestock EEQ, land-applied and irrigated EEQ via surface runoff to water
      environments (0.11 g d) was obviously low compared with the EEQ of LW directly
      released into adjacent waterways (56.7 g d). Therefore, the LW was the major
      contributor to estrogenic risk to the water environment in Shanghai. The spatial
      distribution of estrogen loads indicated that the highest EEQ loads were in the
      southern region of Pudong New Area and the eastern and central regions of
      Fengxian District. 

PMID- 25602659
TI  - Responses of Rat Root ( Raf.) Plants to Salinity and pH Conditions.
AB  - Growth and physiological parameters were examined in rat root ( Raf.) plants
      grown under controlled environment conditions in hydroponics and subjected to
      different pH and salinity treatments to determine whether these environmental
      factors may contribute to poor establishment of in oil sands constructed
      wetlands. When plants were subjected to a root zone pH ranging from 6.0 to 9.5,
      the plants that were growing at pH 7.0 showed the highest relative growth rates
      and chlorophyll concentrations compared with lower and higher pH levels. The
      greatest inhibition of growth occurred at pH ranging from 8.0 to 9.5. High pH
      also triggered significant reductions in tissue concentrations of N, P, and
      microelements, whereas the concentrations of Mg increased at pH >8. When NaCl
      (25, 50, and 100 mmol L) was added to the nutrient solution at pH 7.0 and 8.5,
      higher mortality and greater tissue concentrations of Na and Cl were measured in
      plants growing at pH 8.5 compared with pH 7.0. The results show that plants
      growing at the optimum pH of 7.0 can better tolerate salinity compared with
      plants exposed to high root zone pH. Both pH and salinity may present important
      environmental constraints to growth and establishment of plants in oil sands
      constructed wetlands. 

PMID- 25602660
TI  - Reducing nitrate loss in tile drainage water with cover crops and water-table
      management systems.
AB  - Nitrate lost from agricultural soils is an economic cost to producers, an
      environmental concern when it enters rivers and lakes, and a health risk when it
      enters wells and aquifers used for drinking water. Planting a winter wheat cover
      crop (CC) and/or use of controlled tile drainage-subirrigation (CDS) may reduce
      losses of nitrate (NO) relative to no cover crop (NCC) and/or traditional
      unrestricted tile drainage (UTD). A 6-yr (1999-2005) corn-soybean study was
      conducted to determine the effectiveness of CC+CDS, CC+UTD, NCC+CDS, and NCC+UTD
      treatments for reducing NO loss. Flow volume and NO concentration in surface
      runoff and tile drainage were measured continuously, and CC reduced the 5-yr flow
      weighted mean (FWM) NO concentration in tile drainage water by 21 to 38% and
      cumulative NO loss by 14 to 16% relative to NCC. Controlled tile drainage
      subirrigation reduced FWM NO concentration by 15 to 33% and cumulative NO loss by
      38 to 39% relative to UTD. When CC and CDS were combined, 5-yr cumulative FWM NO
      concentrations and loss in tile drainage were decreased by 47% (from 9.45 to 4.99
      mg N L and from 102 to 53.6 kg N ha) relative to NCC+UTD. The reductions in
      runoff and concomitant increases in tile drainage under CC occurred primarily
      because of increases in near-surface soil hydraulic conductivity. Cover crops
      increased corn grain yields by 4 to 7% in 2004 increased 3-yr average soybean
      yields by 8 to 15%, whereas CDS did not affect corn or soybean yields over the 6
      yr. The combined use of a cover crop and water-table management system was highly
      effective for reducing NO loss from cool, humid agricultural soils. 

PMID- 25602661
TI  - Linking Spatial Variations in Water Quality with Water and Land Management using
      Multivariate Techniques.
AB  - Most studies using multivariate techniques for pollution source evaluation are
      conducted in free-flowing rivers with distinct point and nonpoint sources. This
      study expanded on previous research to a managed "canal" system discharging into
      the Indian River Lagoon, Florida, where water and land management is the single
      most important anthropogenic factor influencing water quality. Hydrometric and
      land use data of four drainage basins were uniquely integrated into the analysis
      of 25 yr of monthly water quality data collected at seven stations to determine
      the impact of water and land management on the spatial variability of water
      quality. Cluster analysis (CA) classified seven monitoring stations into four
      groups (CA groups). All water quality parameters identified by discriminant
      analysis showed distinct spatial patterns among the four CA groups. Two-step
      principal component analysis/factor analysis (PCA/FA) was conducted with (i)
      water quality data alone and (ii) water quality data in conjunction with
      rainfall, flow, and land use data. The results indicated that PCA/FA of water
      quality data alone was unable to identify factors associated with management
      activities. The addition of hydrometric and land use data into PCA/FA revealed
      close associations of nutrients and color with land management and storm-water
      retention in pasture and citrus lands; total suspended solids, turbidity, and NO
      + NO with flow and Lake Okeechobee releases; specific conductivity with
      supplemental irrigation supply; and dissolved O with wetland preservation. The
      practical implication emphasizes the importance of basin-specific land and water
      management for ongoing pollutant loading reduction and ecosystem restoration
      programs. 

PMID- 25602662
TI  - Predicting trihalomethanes in the new york city water supply.
AB  - Chlorine, a commonly used disinfectant in most water supply systems, can combine
      with organic carbon to form disinfectant byproducts, including carcinogenic
      trihalomethanes. We used water quality data from 24 monitoring sites within the
      New York City water supply distribution system, measured between January 2009 and
      April 2012, to develop an empirical model for predicting total trihalomethane
      (TTHM) levels. Terms in the model included the following water quality
      parameters: total organic carbon, pH, water age (reaction time), and water
      temperature. Reasonable estimates of TTHM levels were achieved with overall of
      about 0.75, and predicted values on average were within 6 MUg L of measured
      values. A sensitivity analysis indicated that total organic carbon and water age
      are the most important factors for TTHM formation, followed by water temperature;
      pH was the least important factor within the boundary conditions of observed
      water quality. Although never out of compliance in 2011, the TTHM levels in the
      water supply increased after tropical storms Irene and Lee, with 45% of the
      samples exceeding the 80 MUg L maximum contaminant level in October and November.
      This increase was explained by changes in water quality parameters, particularly
      by the increase in total organic carbon concentration during this period. This
      study demonstrates the use of an empirical model to understand TTHM formative
      factors and their relative importance in a drinking water supply. This has
      implications for simulating management scenarios and real-time estimation of
      TTHMs in water supply systems under changing environmental conditions. 

PMID- 25602663
TI  - Comprehensive nitrogen budgets for controlled tile drainage fields in eastern
      ontario, Canada.
AB  - Excessive N loading from subsurface tile drainage has been linked to water
      quality degradation. Controlled tile drainage (CTD) has the potential to reduce N
      losses via tile drainage and boost crop yields. While CTD can reduce N loss from
      tile drainage, it may increase losses through other pathways. A multiple-year
      field-scale accounting of major N inputs and outputs during the cropping season
      was conducted on freely drained and controlled tile drained agricultural fields
      under corn ( L.)-soybean [ (L.) Merr.] production systems in eastern Ontario,
      Canada. Greater predicted gaseous N emissions for corn and soybean and greater
      observed lateral seepage N losses were observed for corn and soybean fields under
      CTD relative to free-draining fields. However, observed N losses from tile were
      significantly lower for CTD fields, in relation to freely drained fields. Changes
      in residual soil N were essentially equivalent between drainage treatments, while
      mass balance residual terms were systematically negative (slightly more so for
      CTD). Increases in plant N uptake associated with CTD were observed, probably
      resulting in higher grain yields for corn and soybean. This study illustrates the
      benefits of CTD in decreasing subsurface tile drainage N losses and boosting crop
      yields, while demonstrating the potential for CTD to increase N losses via other
      pathways related to gaseous emissions and groundwater seepage. 

PMID- 25602664
TI  - Reconnecting tile drainage to riparian buffer hydrology for enhanced nitrate
      removal.
AB  - Riparian buffers are a proven practice for removing NO from overland flow and
      shallow groundwater. However, in landscapes with artificial subsurface (tile)
      drainage, most of the subsurface flow leaving fields is passed through the
      buffers in drainage pipes, leaving little opportunity for NO removal. We
      investigated the feasibility of re-routing a fraction of field tile drainage as
      subsurface flow through a riparian buffer for increasing NO removal. We
      intercepted an existing field tile outlet draining a 10.1-ha area of a row
      cropped field in central Iowa and re-routed a fraction of the discharge as
      subsurface flow along 335 m of an existing riparian buffer. Tile drainage from
      the field was infiltrated through a perforated pipe installed 75 cm below the
      surface by maintaining a constant head in the pipe at a control box installed in
      line with the existing field outlet. During 2 yr, >18,000 m (55%) of the total
      flow from the tile outlet was redirected as infiltration within the riparian
      buffer. The redirected water seeped through the 60-m-wide buffer, raising the
      water table approximately 35 cm. The redirected tile flow contained 228 kg of NO.
      On the basis of the strong decrease in NO concentrations within the shallow
      groundwater across the buffer, we hypothesize that the NO did not enter the
      stream but was removed within the buffer by plant uptake, microbial
      immobilization, or denitrification. Redirecting tile drainage as subsurface flow
      through a riparian buffer increased its NO removal benefit and is a promising
      management practice to improve surface water quality within tile-drained
      landscapes. 

PMID- 25602665
TI  - Nitrate in shallow groundwater associated with residential land use in central
      Florida.
AB  - The primary objective of this study was to quantify the effects of residential
      fertilizer use on groundwater quality, which have not been well defined by field
      scale investigations. Concentrations of constituents associated with fertilizer
      use were monitored in shallow groundwater in residential areas in Orange and
      Seminole Counties of Central Florida. The study area is within the Wekiva River
      basin, a river that is primarily spring fed. Sampling locations were selected to
      represent land in residential use for more than 5 yr and to avoid septic systems
      and areas recently used for citrus production. Twenty-six wells were installed in
      the surficial aquifer, screened within approximately 3 m of the water table,
      which was encountered between 0.3 and 11.5 m below land surface. Of these wells,
      24 were in residential areas, scattered over an area of about 2600 ha, and two
      were in nearby undeveloped areas. Samples were collected four times between
      October 2008 and July 2009. Concentrations of nitrate plus nitrite nitrogen (NO
      N) averaged 2.0 +/- 0.2 mg L in the residential areas and were significantly
      higher ( < 0.01) than observed in undeveloped areas (0.3 +/- 0.1 mg L).
      Groundwater was also analyzed for stable isotopes of nitrogen and oxygen and has
      been analyzed for bacteria (by others), which corroborated that these wells were
      not affected by human or animal waste. Levels of NO-N in the residential areas
      are primarily attributed to residential fertilizer use, considering the control
      for and exclusion of other plausible sources. 

PMID- 25602666
TI  - Effects of biochar on air and water permeability and colloid and phosphorus
      leaching in soils from a natural calcium carbonate gradient.
AB  - Application of biochar to agricultural fields to improve soil quality has
      increased in popularity in recent years, but limited attention is generally paid
      to existing field conditions before biochar application. This study examined the
      short-term physicochemical effects of biochar amendment in an agricultural field
      in Denmark with a calcium carbonate (CaCO) gradient. The field comprised four
      reference plots and four plots to which biochar (birch wood pyrolyzed at 500
      degrees C) was applied at a rate of 20 t ha. Five undisturbed soil columns (10 cm
      diam., 8 cm height) were sampled from each plot 7 mo after biochar application,
      and a series of leaching experiments was conducted. The leachate was analyzed for
      tritium (used as a tracer), colloids, and phosphorus concentration. The results
      revealed that the presence of CaCO has resulted in marked changes in soil
      structure (bulk density) and soil chemical properties (e.g., pH and ionic
      strength), which significantly affected air and water transport and colloid and
      phosphorous leaching. In denser soils (bulk density, 1.57-1.69 g cm) preferential
      flow dominated the transport and caused an enhanced movement of air and water,
      whereas in less dense soils (bulk density, 1.38-1.52 g cm) matrix flow
      predominated the transport. Compared with reference soils, biochar-amended soils
      showed slightly lower air permeability and a shorter travel time for 5% of the
      applied tracer (tritium) to leach through the soil columns. Colloid and
      phosphorus leaching was observed to be time dependent in soils with low CaCO.
      Biochar-amended soils showed higher colloid and P release than reference soils.
      Field-scale variations in total colloid and P leaching reflected clear effects of
      changes in pH and ionic strength due to the presence of CaCO. There was a linear
      relationship between colloid and P concentrations in the leachate, suggesting
      that colloid-facilitated P leaching was the dominant P transport mechanism. 

PMID- 25602667
TI  - Field-scale monitoring of pharmaceutical compounds applied to active golf courses
      by recycled water.
AB  - The scarcity of potable water in arid and semiarid environments has led to the
      wider use of recycled water for irrigating agricultural fields, parks, golf
      courses, and other areas. One concern using recycled water as a source of
      irrigation has been the presence, fate, and transport of pharmaceutical compounds
      in water that percolates below the root zone of plants; however, very few
      multiyear field studies have been reported in the peer-reviewed literature. Here,
      we assessed compound mass flux of 13 pharmaceuticals in the fairways of four golf
      courses in the southwestern United States during a 2-yr field study. The sites
      varied by climate and soil type but were similar regarding turfgrass management.
      The results showed the presence of at least one pharmaceutical compound in nearly
      all samples collected, although concentrations were substantially lower after
      transport through the soil. Percent reduction in compound mass fluxes in drainage
      water was effectively 100% in 22 of 52 cases, 98 to 100% in 27 of 52 cases, and
      73 to 94% in 3 of 52 cases (a case is defined as a specific compound measured at
      a specific site). Mass fluxes migrating below the root zone were calculated as
      <250 * 10 g ha for all compounds and >100 * 10 g ha in only two cases. For cases
      where the majority of the analyses were reportable, all fluxes were <8.80 * 10 g
      ha. Carbamazepine, meprobamate, and sulfamethoxazole were most commonly found in
      drainage water, representing nearly 80% of all reportable detections. This
      research demonstrates the potential of turfgrass/soil systems to reduce
      contaminant loading below the root zone and potentially toward groundwater. 

PMID- 25602668
TI  - Nitrogen and phosphorus in runoff from cattle manure compost windrows of
      different maturities.
AB  - Manure composting has become commonplace in the beef cattle ( L.) feedlot
      industry in Alberta. However, the nitrogen (N) and phosphorus (P) characteristics
      of runoff from windrows subjected to heavy rainfall at different compost
      maturities are unknown. On Days 18, 26, 40, 54, 81, 109, and 224 of composting, a
      rainfall simulator generated runoff, which was collected in timed 5-L increments,
      creating the variable "time during runoff event" (TDRE). The volumetric runoff
      coefficient of windrows increased from 24% of incident rainfall on Day 0 to 69%
      by Day 90. Ammonium-nitrogen showed a significant maturity * TDRE interaction on
      Day 18, increasing from 46 mg L for the 0- to 5-L increment to 172 mg L for the
      25- to 30-L increment, as did total dissolved phosphorus (TDP), increasing from
      36 to 61 mg L. Nitrate-nitrogen had a runoff export coefficient of 19.5 mg m min
      on Day 224, which was significantly higher than 1.8 to 6.3 mg m min on Days 18 to
      54. Across the 224-d composting period, compost NO-N concentration explained 87%
      of runoff NO-N, whereas compost water-soluble P explained 68% of runoff TDP. The
      occurrence and duration of rainfall events relative to the compost maturity
      spectrum has implications for the magnitude of N and P mobility and overall
      nutrient losses. 

PMID- 25602669
TI  - Hardwood biochar influences calcareous soil physicochemical and microbiological
      status.
AB  - The effects of biochar application to calcareous soils are not well documented.
      In a laboratory incubation study, a hardwood-based, fast pyrolysis biochar was
      applied (0, 1, 2, and 10% by weight) to a calcareous soil. Changes in soil
      chemistry, water content, microbial respiration, and microbial community
      structure were monitored over a 12-mo period. Increasing the biochar application
      rate increased the water-holding capacity of the soil-biochar blend, a trait that
      could be beneficial under water-limited situations. Biochar application also
      caused an increase in plant-available Fe and Mn, soil C content, soil respiration
      rates, and bacterial populations and a decrease in soil NO-N concentration.
      Biochar rates of 2 and 10% altered the relative proportions of bacterial and
      fungal fatty acids and shifted the microbial community toward greater relative
      amounts of bacteria and fewer fungi. The ratio of fatty acid 19:0 cy to its
      precursor, 18:1omega7c, was higher in the 10% biochar rate soil than in all other
      soils, potentially indicating an environmental stress response. The 10%
      application rate of this particular biochar was extreme, causing the greatest
      change in microbial community structure, a physiological response to stress in
      Gram-negative bacteria, and a drastic reduction in soil NO-N (85-97% reduction
      compared with the control), all of which were sustained over time. 

PMID- 25602670
TI  - Characterization of organic matter in beef feedyard manure by ultraviolet-visible
      and fourier transform infrared spectroscopies.
AB  - Manure from beef cattle feedyards is a valuable source of nutrients and assists
      with maintaining soil quality. However, humification and decomposition processes
      occurring during feedyard manure's on-farm life cycle influence the forms,
      concentrations, and availability of carbon (C) and nutrients such as nitrogen (N)
      and phosphorus (P). Improved understanding of manure organic matter (OM)
      chemistry will provide better estimates of potential fertilizer value of manure
      from different feedyard sources (e.g., manure accumulated in pens, stockpiled
      manure after pen scraping) and in settling basin and retention pond sediments.
      This will also assist with identifying factors related to nutrient loss and
      environmental degradation via volatilization of ammonia and nitrous oxide and
      nitrate leaching. We used Fourier-transform infrared (FTIR) and ultraviolet
      visible (UV-vis) spectroscopies to characterize structural and functional
      properties of OM and water-extractable OM (WEOM) from different sources (surface
      manure, manure pack, settling basin, retention pond) on a typical commercial beef
      feedyard in the Texas Panhandle. Results showed that as beef manure completes its
      on-farm life cycle, concentrations of dissolved organic C and N decrease up to 98
      and 95%, respectively. The UV-vis analysis of WEOM indicated large differences in
      molecular weight, lignin content, and proportion of humified OM between manures
      from different sources. The FTIR spectra of OM and WEOM indicate preferential
      decomposition of fats, lipids, and proteins over aromatic polysaccharides such as
      lignin. Further work is warranted to evaluate how application of feedyard manure
      from different sources influences soil metabolic functioning and fertility. 

PMID- 25602671
TI  - Fate of 17beta-estradiol in anaerobic lagoon digesters.
AB  - The fate of [C]17beta-estradiol ([C]E2) was monitored for 42 d in triplicate 10-L
      anaerobic digesters. Total radioactive residues decreased rapidly in the liquid
      layer of the digesters and reached a steady-state value of 22 to 26% of the
      initial dose after 5 d. High-performance liquid chromatography and liquid
      chromatography-tandem mass spectrometry analyses of the liquid layer of the
      anaerobic digesters indicated a rapid degradation of E2 to estrone (E1), which
      readily adsorbed to the sludge layer subsequent to its formation. Estrone was the
      predominant steroid identified under anaerobic digestion in the liquid layer or
      sorbed to sludge at 42 d. Methane formation represented 11.1 +/- 5.7% of the
      initial E2 fortification with 0.3 to 0.5% of the starting E2 mineralized to
      carbon dioxide. Maximum [C]methane production appeared between Days 4 and 7. An
      estimate of estrogenicity of the final product based on reported estrogen
      equivalents for E1 and E2 was 2% of the original in active digesters. Anaerobic
      digestion of swine waste has several management benefits; moreover, this study
      demonstrated that it reduces the potential of environmental release of estrogens,
      which are known endocrine disruptors. 

PMID- 25602672
TI  - Life cycle assessment of fertilization of corn and corn-soybean rotations with
      Swine manure and synthetic fertilizer in iowa.
AB  - Life cycle assessment is the predominant method to compare energy and
      environmental impacts of agricultural production systems. In this life cycle
      study, we focused on the comparison of swine manure to synthetic fertilizer as
      nutrients for corn production in Iowa. Deep pit (DP) and anaerobic lagoon (AL)
      treatment systems were compared separately, and urea ammonium nitrate (UAN) was
      chosen as the representative synthetic fertilizer. The two functional units used
      were fertilization of 1000 kg of corn in a continuous corn system and
      fertilization of a crop yielding 1000 kg of corn and a crop yielding 298 kg of
      soybean in a 2-yr corn-soybean rotation. Iowa-specific versions of emission
      factors and energy use were used when available and compared with
      Intergovernmental Panel on Climate Change values. Manure was lower than synthetic
      fertilizer for abiotic depletion and about equal with respect to eutrophication.
      Synthetic fertilizer was lower than manure for global warming potential (GWP) and
      acidification. The choice of allocation method and life cycle boundary were
      important in understanding the context of these results. In the DP system,
      methane (CH) from housing was the largest contributor to the GWP, accounting for
      60% of the total impact. When storage systems were compared, the DP system had
      50% less GWP than the AL system. This comparison was due to reduction in CH
      emissions from the storage system and conservation of nitrogen. Nitrous oxide
      emissions were the biggest contributor to the GWP of UAN fertilization and the
      second biggest contributor to the GWP of manure. Monte Carlo and scenario
      analyses were used to test the robustness of the results and sensitivity to
      methodology and important impact factors. The available crop-land and associated
      plant nutrient needs in Iowa was compared with manure production for the current
      hog population. On a state- or county-wide level, there was generally an excess
      of available land. On a farm level, there is often an excess of manure, which
      necessitates long-distance transport. 

PMID- 25602673
TI  - Evaluating responses of four wetland plant species to different hydroperiods.
AB  - Previous work has estimated the hydroperiod requirements (saturation duration and
      frequency) of wetland plant communities by modeling their hydrologic regimes in
      natural (never drained) wetlands for a 40-yr period. This study tested the
      modeled predictions in a controlled greenhouse study using tree species
      representing three of the plant communities plus an additional species from
      another community. Bald cypress ( L. Rich.), sweet bay ( L.), pond pine (
      Michx.), and swamp chestnut oak ( Nutt.) were grown under three hydroperiods
      (continuously ponded for 100 d, intermittently ponded for 14 d, and unsaturated)
      in loamy sand and sapric (organic) materials. Bald cypress (representing a
      Nonriverine Swamp Forest community) adapted well to 100 d of ponding by producing
      lateral roots near the soil surface and aerenchyma tissue in roots and stem.
      Sweet bay (Bay Forest community) also adapted well to 100 d of ponding by
      producing adventitious roots on the submerged portion of the stem. Pond pine
      (Pond Pine Woodland) and swamp chestnut oak (Nonriverine Wet Hardwood Forest)
      were intolerant of 100 d of ponded conditions. Seventy-five percent of the pond
      pine seedlings and 87% of the swamp chestnut oak seedlings died in the
      continuously ponded treatment level, whereas 100% of the bald cypress and 88% of
      the sweet bay seedlings survived. Results from this study suggest that modeled
      long-term hydroperiods of natural wetland plant communities can be used for
      restoration of these communities. 

PMID- 25602674
TI  - Shallow groundwater denitrification in riparian zones of a headwater agricultural
      landscape.
AB  - Riparian zones adjacent to cropped lands are effective at reducing nitrate (NO)
      loads to receiving water bodies primarily through plant assimilation and
      denitrification. Denitrification represents a permanent removal pathway and a
      greenhouse gas source, converting NO to inert N gas or nitrous oxide (NO), and
      has been the subject of many studies in agricultural landscapes. Despite the
      prevailing notion that riparian zones can be areas of enhanced denitrification,
      there is a lack of in situ denitrification measurements from these areas that
      buffer streams and rivers from NO originating in upland cropped soils, especially
      over time scales that capture seasonal dynamics. We measured in situ groundwater
      denitrification rates in two riparian zones of an intensive dairy farm located in
      the headwaters of the Susquehanna River. Denitrification rates determined monthly
      over a 1-yr period with the N-NO push-pull method ranged from 0 to 4177 MUg N kg
      soil d (mean, 830 +/- 193 MUg N kg soil d). Denitrification showed a distinct
      seasonal pattern, with highest rates observed in the spring and summer,
      concomitant with warmer temperatures and decreasing dissolved oxygen. We estimate
      an annual N loss of 470 +/- 116 kg yr ha of riparian zone via denitrification in
      the shallow saturated zone, with the potential for >20% of this amount occurring
      as NO. Total denitrification from shallow groundwater in the riparian zone was
      equivalent to 32% of manure N spread on the adjacent upland field, confirming the
      importance of riparian zones in agricultural landscapes at controlling N loads
      entering downstream waters. 

PMID- 25602675
TI  - Vertical dissolved inorganic nitrogen fluxes in marsh and mudflat areas of the
      yangtze estuary.
AB  - Nitrogen (N) is a dominant macronutrient in many river-dominated coastal systems,
      and excess concentrations can drive eutrophication, the effects of which can
      include hypoxia and algal blooms. The Yangtze River in China transports a large
      amount of dissolved inorganic N. Therefore, it is important to understand the
      role of the marsh and mudflat areas within the estuary on processing this
      exogenous N load. In situ dissolved inorganic nitrogen (DIN) fluxes across the
      sediment-water interface were determined monthly at Chongming Island at two sites
      (a vegetated marsh and an unvegetated mudflat) and were compared with rates from
      a previously published laboratory incubation study by our research group. Results
      from the in situ study showed that NO flux rates comprised the major component of
      total DIN flux, ranging from 55 to 97%. No significant difference was observed in
      the N flux rates between the marsh and mudflat sites. Overall, sediment at both
      sites served as a sink of DIN from surface water with mean flux rates of -178
      MUmol m h and -165 MUmol m h for the marsh and mudflat, respectively. In general,
      DIN flux rates were not significantly correlated with DIN concentrations and
      other measured parameters (temperature, dissolved oxygen, salinity, and pH) of
      surface water. The in situ measured fluxes of NO and NO in this study were not
      significantly different from those of our previous laboratory incubation ( >
      0.05), whereas NH fluxes in situ were significantly lower than those from the
      laboratory core incubations ( < 0.05). This result suggests that caution should
      be used when extrapolating rates from laboratory incubation methods to the field
      because the rates might not be equivalent. 

PMID- 25602676
TI  - Reducing monitoring costs in industrially contaminated rivers: cluster and
      regression analysis approach.
AB  - Monitoring contamination in river water is an expensive procedure, particularly
      for developing countries where pollution is a significant problem. This study was
      conducted to provide a pollution monitoring strategy that reduces the cost of
      laboratory analysis. The new monitoring strategy was designed as a result of
      cluster and regression analysis on field data collected from an industrially
      influenced river. Pollution sources in the study site were coal mining,
      metallurgy, chemical industry, and metropolitan sewage. This river resembles
      those in other areas of the world, including developing countries where
      environmental monitoring is financially constrained. Data were collected on
      variability of contaminant concentrations during four seasons at the same points
      on tributaries of the river. The variables described in the study are pH,
      electrical conductivity, inorganic ions, trace elements, and selected organic
      pollutants. These variables were divided into groups using cluster analysis.
      These groups were then tested using regression models to identify how the
      behavior of one variable changes in relation to another. It was found that up to
      86.8% of variability of one parameter could be determined by another in the
      dataset. We adopted 60, 65, and 70% determination levels () for accepting a
      regression model. As a result, monitoring could be reduced by 15 (60% level) and
      10 variables (65 and 70%) out of 43, which comprises 35 and 23% of the monitored
      variable total. Cost reduction would be most effective if trace elements or
      organic pollutants were excluded from monitoring because these are the
      constituents most expensive to analyze. 

PMID- 25602678
TI  - Biochar and manure affect calcareous soil and corn silage nutrient concentrations
      and uptake.

PMID- 25602677
TI  - Mathematical decision theory applied to land capability: a case study in the
      community of madrid.
AB  - In land evaluation science, a standard data set is obtained for each land unit to
      determine the land capability class for various uses, such as different farming
      systems, forestry, or the conservation or suitability of a specific crop. In this
      study, we used mathematical decision theory (MDT) methods to address this task.
      Mathematical decision theory has been used in areas such as management, finance,
      industrial design, rural development, the environment, and projects for future
      welfare to study quality and aptness problems using several criteria. We also
      review MDT applications in soil science and discuss the suitability of MDT
      methods for dealing simultaneously with a number of problems. The aim of the work
      was to show how MDT can be used to obtain a valid land quality index and to
      compare this with a traditional land capability method. Therefore, an additive
      classification method was applied to obtain a land quality index for 122 land
      units that were compiled for a case study of the Community of Madrid, Spain, and
      the results were compared with a previously assigned land capability class using
      traditional methods based on the minimum requirements for land attributes. 

PMID- 25602679
TI  - Dually fixed SnO2 nanoparticles on graphene nanosheets by polyaniline coating for
      superior lithium storage.
AB  - Dually fixed SnO2 nanoparticles (DF-SnO2 NPs) on graphene nanosheets by a
      polyaniline (Pani) coating was successfully fabricated via two facile wet
      chemistry processes, including anchoring SnO2 NPs onto graphene nanosheets via
      reducing graphene oxide by Sn(2+) ion, followed by in situ surface sealing with
      the Pani coating. Such a configuration is very appealing anode materials in LIBs
      due to several structural merits: (1) it prevents the aggregation of SnO2 NPs,
      (2) accommodates the structural expanding of SnO2 NPs during lithiation, (3)
      ensures the stable as-formed solid electrolyte interface films, and (4)
      effectively enhances the electronic conductivity of the overall electrode.
      Therefore, the final DF-SnO2 anode exhibits stable cycle performance, such as a
      high capacity retention of over 90% for 400 cycles at a current density of 200 mA
      g(-1) and a long cycle life up to 700 times at a higher current density of 1000
      mA g(-1). 

PMID- 25602680
TI  - Critical care evidence--new directions.

PMID- 25602682
TI  - Novel angiogenesis inhibitors in nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: The fact that growth and spread of tumours are dependent on
      angiogenesis has led to the investigation of the role of antiangiogenic agents in
      the therapeutic strategies for thoracic tumours such as nonsmall cell lung cancer
      (NSCLC). This review summarizes and evaluates the recent developments in this
      field. RECENT FINDINGS: Bevacizumab, an antivascular endothelial growth factor
      antibody, has been approved for the treatment of patients with advanced NSCLC of
      nonsquamous histology in combination with a platinum-containing chemotherapy.
      Like in other cancer entities, the antiangiogenic concept in NSCLC comprises
      maintenance therapy with the antiangiogenic compound until disease progression.
      Moreover, over the last years, new antiangiogenic agents have been tested in
      clinical trials in NSCLC patients. Recent trials have demonstrated the efficacy
      of antiangiogenic agents in combination with docetaxel in the second-line
      setting. SUMMARY: These studies - together with experiences from other cancer
      entities - have revived the field of antiangiogenic treatment in lung cancer.

PMID- 25602683
TI  - Immune checkpoint inhibitors in advanced nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: Targeting immune checkpoints has led to promising results in
      metastatic nonsmall cell lung cancer (NSCLC). By restoring antitumor immunity,
      these treatments are able to induce prolonged clinical responses. The level of
      activity and the durability of responses observed in phase I trials has led most
      companies to launch phases II and III trials whose results are highly expected.
      RECENT FINDINGS: In this review, we present efficacy and toxicity results of the
      different immune checkpoint inhibitors (ICIs) currently developed in NSCLC and
      report other checkpoints currently explored. The specific profile of tumor
      responses and immune-related toxicity observed with immunotherapy will be
      addressed. Finally, to illustrate the new insights into the development of these
      drugs, we will give an overview of the different ICIs combination studies
      evaluated in NSCLC and will discuss the role of programmed cell death-L1 as a
      potential biomarker. SUMMARY: This review will address some of the future
      challenges of ICIs in NSCLC.

PMID- 25602681
TI  - Select host restriction factors are associated with HIV persistence during
      antiretroviral therapy.
AB  - OBJECTIVE: The eradication of HIV necessitates elimination of the HIV latent
      reservoir. Identifying host determinants governing latency and reservoir size in
      the setting of antiretroviral therapy (ART) is an important step in developing
      strategies to cure HIV infection. We sought to determine the impact of cell
      intrinsic immunity on the HIV latent reservoir. DESIGN: We investigated the
      relevance of a comprehensive panel of established anti-HIV-1 host restriction
      factors to multiple established virologic and immunologic measures of viral
      persistence in HIV-1-infected, ART-suppressed individuals. METHODS: We measured
      the mRNA expression of 42 anti-HIV-1 host restriction factors, levels of cell
      associated HIV-1 RNA, levels of total pol and 2-long terminal repeat (2-LTR)
      circle HIV-1 DNA and immunophenotypes of CD4 T cells in 72 HIV-1-infected
      individuals on suppressive ART (23 individuals initiated ART less than 1 year
      post-infection, and 49 individuals initiated ART greater than 1 year post
      infection). Correlations were analysed using nonparametric tests. RESULTS: The
      enhanced expression of a few select host restriction factors, p21, schlafen 11
      and PAF1, was strongly associated with reduced CD4 T-cell associated HIV RNA
      during ART (P < 0.001). In addition, our data suggested that ART perturbs the
      regulatory relationship between CD4 T-cell activation and restriction factor
      expression. Lastly, cell-intrinsic immune responses were significantly enhanced
      in individuals who initiated ART during early versus chronic infection and may
      contribute to the reduced reservoir size observed in these individuals.
      CONCLUSION: Intrinsic immune responses modulate HIV persistence during
      suppressive ART and may be manipulated to enhance the efficacy of ART and promote
      viral eradication through reversal of latency in vivo.

PMID- 25602684
TI  - Combination therapy of melanoma using kinase inhibitors.
AB  - PURPOSE OF REVIEW: Treatment options for metastatic melanoma depend on the
      clinical course of the disease and the molecular profile such as mutations of the
      BRAF gene. In this article, we review the current state of targeted therapy with
      kinase inhibitors. RECENT FINDINGS: Despite major advancements in targeted
      therapy of metastatic melanoma, most patients relapse and show progressive
      disease after 5-7 months with single inhibition of BRAF or MEK. Acquired
      resistance is virtually universal and mediated by diverse mitogen-activated
      protein kinase-dependent or independent mechanisms. Recent evidence favours
      concurrent targeting of BRAF and MEK in patients with BRAFV600-mutated melanoma
      instead of BRAF inhibitor monotherapy. The combination delays the onset of
      acquired resistance, resulting in increased progression-free and overall
      survival. A growing number of early trials evaluate the efficacy of inhibitors
      targeting additional pathways such as phospho-inositide 3-kinase/AKT in
      conjunction with BRAF or MEK. Even though consistent and mature phase III study
      results are not yet available for these combinations, the repertoire of targeted
      therapy in metastatic melanoma is wide and promising. SUMMARY: The short era of
      single BRAF inhibition in BRAF-mutated melanoma is soon taken over by dual
      concurrent inhibition of MEK and BRAF.

PMID- 25602685
TI  - Numerical simulation on the effects of drug eluting stents at different Reynolds
      numbers on hemodynamic and drug concentration distribution.
AB  - BACKGROUND: The changes of hemodynamics and drug concentration distribution
      caused by the implantation of drug eluting stents (DESs) in curved vessels have
      significant effects on In-Stent Restenosis. METHODS: A 3D virtual stent with 90
      degrees  curvature was modelled and the distribution of wall shear stress (WSS)
      and drug concentration in this model were numerically studied at Reynolds numbers
      of 200, 400, 600, 800. RESULTS: The results showed that (1) the intensity of
      secondary flow at the 45 degrees  cross-section was stronger than that at the 90
      degrees  cross-section; (2) As the Reynolds number increases, the WSS decreases.
      When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of
      the total area. (3) The effects of Reynolds number on drug concentration in the
      vascular wall decreases in proportionally and then the blood velocity increased 4
      times, the drug concentration in the vascular wall decreased by about 30%. (4)
      The size of the high drug concentration region is inversely proportional to the
      Reynolds number. As the blood velocity increases, the drug concentration in the
      DES decreases, especially at the outer bend. CONCLUSIONS: It is beneficial for
      the patient to decrease vigorous activities and keep calm at the beginning of the
      stent implantation, because a substantial amount of the drug is released in the
      first two months of stent implantation, thus a calm status is conducive to drug
      release and absorption; Subsequently, appropriate exercise which increases the
      blood velocity is helpful in decreasing regions of low-WSS.

PMID- 25602686
TI  - A robust adaptive sampling method for faster acquisition of MR images.
AB  - A robust adaptive k-space sampling method is proposed for faster acquisition and
      reconstruction of MR images. In this method, undersampling patterns are generated
      based on magnitude profile of a fully acquired 2-D k-space data. Images are
      reconstructed using compressive sampling reconstruction algorithm. Simulation
      experiments are done to assess the performance of the proposed method under
      various signal-to-noise ratio (SNR) levels. The performance of the method is
      better than non-adaptive variable density sampling method when k-space SNR is
      greater than 10dB. The method is implemented on a fully acquired multi-slice raw
      k-space data and a quality assurance phantom data. Data reduction of up to 60% is
      achieved in the multi-slice imaging data and 75% is achieved in the phantom
      imaging data. The results show that reconstruction accuracy is improved over non
      adaptive or conventional variable density sampling method. The proposed sampling
      method is signal dependent and the estimation of sampling locations is robust to
      noise. As a result, it eliminates the necessity of mathematical model and
      parameter tuning to compute k-space sampling patterns as required in non-adaptive
      sampling methods. 

PMID- 25602687
TI  - Oligonol supplementation modulates plasma volume and osmolality and sweating
      after heat load in humans.
AB  - Oligonol is a low-molecular-weight polyphenol that possesses antioxidant and anti
      inflammatory properties. This study investigated the effects of Oligonol
      supplementation on sweating response, plasma volume (PV), and osmolality (Osm)
      after heat load in human volunteers. We conducted a placebo-controlled crossover
      trial. Participants took a daily dose of 200 mg Oligonol or placebo for 1 week.
      After a 2-week washout period, the subjects were switched to the other study arm.
      As a heat load, half-body immersion into hot water (42 degrees C+/-0.5 degrees C
      for 30 min) was performed in an automated climate chamber. Tympanic and mean body
      temperature (Tty, mTb) and whole-body sweat loss volume (WBSLV) were measured.
      Changes in PV, Osm, and serum levels of aldosterone and sodium were analyzed.
      Oligonol intake attenuated increases in Tty, mTb, and WBSLV after heat load
      compared with the placebo (P<.01, P<.05, and P<.01, respectively). In addition,
      serum aldosterone was maintained at a relatively low degree and serum sodium was
      maintained at a relatively high degree with Oligonol compared to the placebo
      (P<.01 and P<.05, respectively). However, PV decreased and Osm increased
      significantly with Oligonol compared to the placebo (P<.05 and P<.05,
      respectively). This study demonstrates that Oligonol supplementation for 1 week
      can attenuate elevation of body temperature and excessive sweating under heat
      load in healthy humans, but interpretation of the results requires caution due to
      the potent diuretic effect of Oligonol.

PMID- 25602688
TI  - Extraordinary improvement of gas-sensing performances in SnO2 nanofibers due to
      creation of local p-n heterojunctions by loading reduced graphene oxide
      nanosheets.
AB  - We propose a novel approach to improve the gas-sensing properties of n-type
      nanofibers (NFs) that involves creation of local p-n heterojunctions with p-type
      reduced graphene oxide (RGO) nanosheets (NSs). This work investigates the sensing
      behaviors of n-SnO2 NFs loaded with p-RGO NSs as a model system. n-SnO2 NFs
      demonstrated greatly improved gas-sensing performances when loaded with an
      optimized amount of p-RGO NSs. Loading an optimized amount of RGOs resulted in a
      20-fold higher sensor response than that of pristine SnO2 NFs. The sensing
      mechanism of monolithic SnO2 NFs is based on the joint effects of modulation of
      the potential barrier at nanograin boundaries and radial modulation of the
      electron-depletion layer. In addition to the sensing mechanisms described above,
      enhanced sensing was obtained for p-RGO NS-loaded SnO2 NFs due to creation of
      local p-n heterojunctions, which not only provided a potential barrier, but also
      functioned as a local electron absorption reservoir. These mechanisms markedly
      increased the resistance of SnO2 NFs, and were the origin of intensified
      resistance modulation during interaction of analyte gases with preadsorbed oxygen
      species or with the surfaces and grain boundaries of NFs. The approach used in
      this work can be used to fabricate sensitive gas sensors based on n-type NFs. 

PMID- 25602689
TI  - Are dietary antioxidant intake indices correlated to oxidative stress and
      inflammatory marker levels?
AB  - Epidemiologic and experimental studies have shown that a high intake of
      individual dietary antioxidants is associated with a reduced risk of cancers. Few
      studies, however, have investigated the influences of a combination of dietary
      antioxidants. We evaluated the association of two dietary antioxidant indices,
      the Dietary Antioxidant Quality Score (DAQS) and the Composite Dietary
      Antioxidant Index (CDAI), with 10 oxidative stress or inflammation biomarkers
      (urinary F2-isoprostanes [15-F2t-IsoP]; urinary F2-isoprostane metabolites [15
      F2t-IsoPM]; urinary prostaglandin E2 metabolite [PGEM]; C-reactive protein [CRP];
      interleukin-1beta [IL-1beta]; interleukin-6 [IL-6]; tumor necrosis factor-alpha
      [TNF-alpha]; soluble TNF-receptor 1 [sTNF-R1]; soluble TNF-receptor 2 [sTNF-R2];
      and soluble GP130 [sGP130]) in 3853 participants of the Shanghai Women's Health
      Study (SWHS). We found the DAQS and CDAI to be highly correlated (r=0.72), and
      both were inversely associated with levels of IL-1beta (ptrend=0.02 and 0.03,
      respectively) and TNF-alpha (ptrend=0.005 and 0.003, respectively). In addition,
      IL-6 and sTNF-R2 levels were inversely associated with the DAQS score; beta
      coefficient(+/-SE) for average-quality and high-quality group versus low-quality
      group were -0.22(+/-0.13) and -0.30(+/-0.13) (ptrend=0.06) for IL-6; -0.06(+/
      0.04) and -0.10(+/-0.04) (ptrend=0.01) for sTNF-R2. Neither the DAQS nor CDAI
      score was significantly associated with oxidative stress or other inflammatory
      biomarkers. Our observations lead us to hypothesize that these two indices offer
      a potential aggregate method of measuring dietary anti-inflammation, but not anti
      oxidation properties.

PMID- 25602690
TI  - Further clarifying prospective and inhibitory intolerance of uncertainty:
      Factorial and construct validity of test scores from the Intolerance of
      Uncertainty Scale.
AB  - The Intolerance to Uncertainty Scale (IUS) was developed to measure a
      dispositional tendency to react negatively to uncertain events, regardless of the
      occurrence probability of those events. Recent evidence suggests a 2-factor
      structure underlying the IUS; 1 factor measuring a prospective aspect (i.e.,
      desire for predictability) and the other assessing an inhibitory aspect (i.e.,
      uncertainty paralysis). The factorial and construct validity of the IUS test
      scores among undergraduate students in Singapore were examined in the present
      research using exploratory (n = 565) and confirmatory (n = 898) factor analyses.
      Results indicated that a 2-factor model was preferred over a unitary-factor
      model. The construct validity of the IUS (and subscale) scores was examined using
      a comprehensive nomological network of psychopathology and
      personality/affectivity variables. Differential relations were observed for the
      prospective and inhibitory components, providing support that the 2 subscales
      assessed unique aspects of the intolerance of uncertainty construct. An 18-item
      modified version of IUS was also proposed and its test scores had stronger
      validity evidence than scores from the widely used 12-item version.

PMID- 25602691
TI  - The South African Personality Inventory (SAPI): a culture-informed instrument for
      the country's main ethnocultural groups.
AB  - We present the development and the underlying structure of a personality
      inventory for the main ethnocultural groups of South Africa, using an emic-etic
      approach. The South African Personality Inventory (SAPI) was developed based on
      an extensive qualitative study of the implicit personality conceptions in the
      country's 11 official languages (Nel et al., 2012). Items were generated and
      selected (to a final set of 146) with a continuous focus on cultural adequacy and
      translatability. Students and community adults (671 Blacks, 198 Coloreds, 104
      Indians, and 391 Whites) completed the inventory. A 6-dimensional structure
      (comprising a positive and a negative Social-Relational factor, Neuroticism,
      Extraversion, Conscientiousness, and Openness) was equivalent across groups and
      replicated in an independent sample of 139 Black and 270 White students. The SAPI
      correlated highly overall with impression-management aspects, but lower with
      lying aspects of social desirability. The SAPI social-relational factors were
      distinguishable from the Big Five in a joint factor analysis; the multiple
      correlations with the Big Five were .64 (positive) and .51 (negative social
      relational). Implications and suggestions for emic-etic instrument and model
      development are discussed.

PMID- 25602692
TI  - Psychometric validation of the Dysexecutive Questionnaire (DEX).
AB  - This study reported on the validation of the psychometric properties, the
      factorability, validity, and sensitivity of the Dysexecutive Questionnaire (DEX)
      in 3 clinical and nonclinical samples. A mixed sample of 997 participants-
      community (n = 663), psychiatric (depressed [n = 92] and anxious [n = 122]), and
      neurologically impaired (n = 120)--completed self-report questionnaires assessing
      executive dysfunction, depression, anxiety, stress, general self-efficacy, and
      satisfaction with life. Before analyses the data were randomly split into 2
      subsets (A and B). Exploratory factor analysis performed on Subset A produced a 3
      factor model (Factor 1: Inhibition, Factor 2: Volition, and Factor 3: Social
      Regulation) in which 15 of the original 20 items provided a revised factor
      structure that was superior to all other structures. A series of confirmatory
      factor analyses performed on Subset B confirmed that this revised factor
      structure was valid and reliable. The revised structure, labeled the DEX-R, was
      found to be a reliable and valid tool for assessing behavioral symptoms of
      dysexecutive functioning in mixed community, psychiatric, and neurological
      samples.

PMID- 25602693
TI  - The dimensionality of defense-mechanism parcels in the Defense Style
      Questionnaire-40.
AB  - The Defense Style Questionnaire-40 (DSQ-40; Andrews, Singh, & Bond, 1993) uses
      pairs of items to measure 20 individual defense mechanisms. In a statistical
      sense, these item pairs represent parcels and are subject to the standards of
      unidimensionality demanded of parcels in general. Using a 2-facet modeling
      approach (N = 672), the present study examined the dimensionality of the defense
      mechanism parcels in the DSQ-40 and found that the majority of the parcels did
      not satisfy the criteria for unidimensionality. In addition, the original 3
      factor model of defense styles was not tenable with the present data. Overall,
      the results suggest caution when attempting to assess individual defense
      mechanisms using the DSQ-40.

PMID- 25602694
TI  - Assessing youth offenders in a non-Western context: The predictive validity of
      the YLS/CMI ratings.
AB  - Empirical support for the usage of the Youth Level of Service measures has been
      reported in studies conducted in the North America, United Kingdom, and
      Australia. Recent meta-analytic studies on the Youth Level of Service/Case
      Management Inventory (YLS/CMI) have revealed that the measure has modest to
      moderate predictive validity for general recidivism, but there are very few
      studies on the predictive validity of the YLS/CMI ratings for recidivism in non
      Western contexts. This study examined the predictive validity of the YLS/CMI 2.0
      ratings for general recidivism in a sample of 3,264 youth offenders within a
      Singaporean context (Mfollow-up = 1,764.5 days; SDfollow-up = 521.5). Results
      showed that the YLS/CMI 2.0 overall risk ratings and total scores significantly
      predicted general recidivism for both male and female youth offenders. Overall,
      the results suggest that the YLS/CMI 2.0 is suited for assessing youth offenders
      in terms of their risk for general recidivism within a non-Western context.

PMID- 25602695
TI  - Integrated satellite data fusion and mining for monitoring lake water quality
      status of the Albufera de Valencia in Spain.
AB  - Lake eutrophication is a critical issue in the interplay of water supply,
      environmental management, and ecosystem conservation. Integrated sensing,
      monitoring, and modeling for a holistic lake water quality assessment with
      respect to multiple constituents is in acute need. The aim of this paper is to
      develop an integrated algorithm for data fusion and mining of satellite remote
      sensing images to generate daily estimates of some water quality parameters of
      interest, such as chlorophyll a concentrations and water transparency, to be
      applied for the assessment of the hypertrophic Albufera de Valencia. The Albufera
      de Valencia is the largest freshwater lake in Spain, which can often present
      values of chlorophyll a concentration over 200 mg m(-3) and values of
      transparency (Secchi Disk, SD) as low as 20 cm. Remote sensing data from Moderate
      Resolution Imaging Spectroradiometer (MODIS) and Landsat Thematic Mapper (TM) and
      Enhance Thematic Mapper (ETM+) images were fused to carry out an integrative near
      real time water quality assessment on a daily basis. Landsat images are useful to
      study the spatial variability of the water quality parameters, due to its spatial
      resolution of 30 m, in comparison to the low spatial resolution (250/500 m) of
      MODIS. While Landsat offers a high spatial resolution, the low temporal
      resolution of 16 days is a significant drawback to achieve a near real-time
      monitoring system. This gap may be bridged by using MODIS images that have a high
      temporal resolution of 1 day, in spite of its low spatial resolution. Synthetic
      Landsat images were fused for dates with no Landsat overpass over the study area.
      Finally, with a suite of ground truth data, a few genetic programming (GP) models
      were derived to estimate the water quality using the fused surface reflectance
      data as inputs. The GP model for chlorophyll a estimation yielded a R(2) of 0.94,
      with a Root Mean Square Error (RMSE) = 8 mg m(-3), and the GP model for water
      transparency estimation using Secchi disk showed a R(2) of 0.89, with an RMSE = 4
      cm. With this effort, the spatiotemporal variations of water transparency and
      chlorophyll a concentrations may be assessed simultaneously on a daily basis
      throughout the lake for environmental management.

PMID- 25602696
TI  - Mechanisms of antimony adsorption onto soybean stover-derived biochar in aqueous
      solutions.
AB  - Limited mechanistic knowledge is available on the interaction of biochar with
      trace elements (Sb and As) that exist predominantly as oxoanions. Soybean stover
      biochars were produced at 300  degrees C (SBC300) and 700  degrees C (SBC700),
      and characterized by BET, Boehm titration, FT-IR, NMR and Raman spectroscopy.
      Bound protons were quantified by potentiometric titration, and two acidic sites
      were used to model biochar by the surface complexation modeling based on Boehm
      titration and NMR observations. The zero point of charge was observed at pH 7.20
      and 7.75 for SBC300 and SBC700, respectively. Neither antimonate (Sb(V)) nor
      antimonite (Sb(III)) showed ionic strength dependency (0.1, 0.01 and 0.001 M
      NaNO3), indicating inner sphere complexation. Greater adsorption of Sb(III) and
      Sb(V) was observed for SBC300 having higher -OH content than SBC700. Sb(III)
      removal (85%) was greater than Sb(V) removal (68%). Maximum adsorption density
      for Sb(III) was calculated as 1.88 * 10(-6) mol m(-2). The Triple Layer Model
      (TLM) successfully described surface complexation of Sb onto soybean stover
      derived biochar at pH 4-9, and suggested the formation of monodentate mononuclear
      and binuclear complexes. Spectroscopic investigations by Raman, FT-IR and XPS
      further confirmed strong chemisorptive binding of Sb to biochar surfaces.

PMID- 25602697
TI  - MelanA-negative spindle-cell associated melanoma, a distinct inflammatory
      phenotype correlated with dense infiltration of CD163 macrophages and loss of E
      cadherin.
AB  - MelanA is a known melanocyte marker and is important in melanoma diagnostics.
      Some tumours, however, show loss of MelanA expression and may therefore be
      difficult to distinguish from tumours of mesenchymal origin. Pure spindle-cell
      melanoma is a rare event, and little is known about its biological background and
      prognosis. However, morphological changes towards a more mesenchymal shape and
      cellular dedifferentiation may correlate with reactivation of important
      developmental programmes (epithelial-to-mesenchymal transition) and disseminative
      tumour cell properties. Inflammation and CD163+ macrophages have been shown to be
      important inducers of E-cadherin and cell-to-cell adhesion loss, a pivotal and
      final event of epithelial-to-mesenchymal transition. In a cohort of 385 patients
      with melanoma, we located nine tumours with a clonal MelanA expression, defined
      as a tumour section with a distinct MelanA-negative clone next to a MelanA
      positive clone. Interestingly, MelanA-negative clones correlated significantly
      with an augmented inflammatory response of tumour-infiltrating macrophages
      (CD163+), complete loss of E-cadherin and a spindle-shaped morphology,
      irrespective of ulcerated status. These cases show the inflammatory heterogeneity
      of melanoma, which may have important diagnostic, prognostic and therapeutic
      implications for the patients. We show that melanomas harbour cell clones that
      bear strong resemblance to tumour-associated macrophages, a pivotal player in a
      tumour-supporting microenvironment. Interestingly, this distinct inflammatory
      phenotype is associated with loss of MelanA expression, the presence of spindle
      shape morphology and complete loss of E-cadherin, considered as possible markers
      of poorly differentiated and more invasive tumour cells. 

PMID- 25602698
TI  - Hemostasis and thrombosis in trauma patients.
AB  - Hemostasis and thrombosis in trauma patients consist of physiological hemostasis
      for wound healing and the pathological reaction of disseminated intravascular
      coagulation (DIC). Whole body trauma, isolated brain injury, and fat embolism
      syndrome, if extremely severe, can cause DIC and affect a patient's prognosis.
      Shock-induced hyperfibrinolysis causes DIC with the fibrinolytic phenotype,
      contributing to oozing-type severe bleeding. If uncontrolled, this phenotype
      progresses to thrombotic phenotype at the late stage of trauma, followed by
      microvascular thrombosis, leading to organ dysfunction. Another type of
      pathological hemostatic change is acute coagulopathy of trauma shock (ACOTS),
      which gives rise to activated protein C-mediated systemic hypocoagulation,
      resulting in bleeding. ACOTS occurs only in trauma associated with shock-induced
      hypoperfusion and there is nothing to suggest DIC in this phenomenon. This review
      will provide information about the recent advances in hemostasis and thrombosis
      in trauma and will clarify the pathogeneses of the pathological processes
      observed in trauma patients. 

PMID- 25602700
TI  - Structure and heme-binding properties of HemQ (chlorite dismutase-like protein)
      from Listeria monocytogenes.
AB  - Chlorite dismutase-like proteins are structurally closely related to functional
      chlorite dismutases which are heme b-dependent oxidoreductases capable of
      reducing chlorite to chloride with simultaneous production of dioxygen. Chlorite
      dismutase-like proteins are incapable of performing this reaction and their
      biological role is still under discussion. Recently, members of this large
      protein family were shown to be involved in heme biosynthesis in Gram-positive
      bacteria, and thus the protein was renamed HemQ in these organisms. In the
      present work the structural and heme binding properties of the chlorite dismutase
      like protein from the Gram-positive pathogen Listeria monocytogenes (LmCld) were
      analyzed in order to evaluate its potential role as a regulatory heme sensing
      protein. The homopentameric crystal structure (2.0A) shows high similarity to
      chlorite-degrading chlorite dismutases with an important difference in the
      structure of the putative substrate and heme entrance channel. In solution LmCld
      is a stable hexamer able to bind the low-spin ligand cyanide. Heme binding is
      reversible with KD-values determined to be 7.2MUM (circular dichroism
      spectroscopy) and 16.8MUM (isothermal titration calorimetry) at pH 7.0. Both
      acidic and alkaline conditions promote heme release. Presented biochemical and
      structural data reveal that the chlorite dismutase-like protein from L.
      monocytogenes could act as a potential regulatory heme sensing and storage
      protein within heme biosynthesis. 

PMID- 25602701
TI  - Elastic proteins in the flight muscle of Manduca sexta.
AB  - The flight muscles (DLM1) of the Hawkmoth, Manduca sexta are synchronous,
      requiring a neural spike for each contraction. Stress/strain curves of skinned
      DLM1 showed hysteresis indicating the presence of titin-like elastic proteins.
      Projectin and kettin are titin-like proteins previously identified in Lethocerus
      and Drosophila flight muscles. Analysis of Manduca muscles with 1% SDS-agarose
      gels and western blots showed two bands near 1 MDa that cross-reacted with
      antibodies to Drosophila projectin. Antibodies to Drosophila kettin cross-reacted
      to bands at ~500 and ~700 kDa, but also to bands at ~1.6 and ~2.1 MDa, that had
      not been previously observed in insect flight muscles. Mass spectrometry
      identified the 2.1 MDa protein as a product of the Sallimus (sls) gene. Analysis
      of the gene sequence showed that all 4 putative Sallimus and kettin isoforms
      could be explained as products of alternative splicing of the single sls gene.
      Both projectin and sallimus isoforms were expressed to higher levels in ventrally
      located DLM1 subunits, primarily responsible for active work production, as
      compared to dorsally located subunits, which may act as damped springs. The
      different expression levels of the 2 projectin isoforms and 4 sallimus/kettin
      isoforms may be adaptations to the specific requirements of individual muscle
      subunits.

PMID- 25602702
TI  - Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat
      model.
AB  - Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in
      humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a
      unique animal model to study RCC since these rats develop spontaneous renal
      tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation
      resulting in the activation of the mammalian target of rapamycin (mTOR) pathway.
      This study examines the role of a lycopene-rich diet in the development of RCC in
      the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n=90) were
      assigned in equal numbers to receive 0, 100 or 200mg/kg of lycopene as part of
      their daily diet. After 18 months the rats were sacrificed and the kidneys were
      removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6
      and EGFR were performed, as well as hematoxylin-eosin staining for histologic
      examination of the tumors. Tumors were counted and measured in individual
      kidneys. Presence of tumor decreased from 94% in control animals to 65% in the
      experimental group, but the difference was not statistically significant
      (P<0.12). However, mean numbers of renal carcinomas were statistically
      significantly decreased in the lycopene-treated rats (P<0.008) when compared to
      untreated controls. In the lycopene group, tumor numbers decreased (P<0.002) and
      the numbers tended to decrease linearly (P<0.003) as supplemental lycopene
      increased from 0 to 200. Control rats fed only basal diet had a greater length of
      tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07
      mm) (P<0.05). Moreover tumor length decreased (P<0.02) and tumor length tended to
      decrease linearly (P<0.03) as supplemental lycopene increased from 0 to 200mg/kg.
      All tumors showed strong staining with antibodies against mTOR, phospho-S6 and
      EGFR. In conclusion, dietary supplementation with lycopene attenuates the
      development of renal cell cancers in the predisposed TSC2 mutant Eker rat model.
      These results suggest that lycopene may play a role in the prevention of RCC.

PMID- 25602703
TI  - Actions of beta-apo-carotenoids in differentiating cells: differential effects in
      P19 cells and 3T3-L1 adipocytes.
AB  - beta-Apo-carotenoids, including beta-apo-13-carotenone and beta-apo-14'
      carotenal, are potent retinoic acid receptor (RAR) antagonists in transactivation
      assays. We asked how these influence RAR-dependent processes in living cells.
      Initially, we explored the effects of beta-apo-13-carotenone and beta-apo-14'
      carotenal on P19 cells, a mouse embryonal carcinoma cell line that differentiates
      into neurons when treated with all-trans-retinoic acid. Treatment of P19 cells
      with either compound failed to block all-trans-retinoic acid induced
      differentiation. Liquid chromatography tandem mass spectrometry studies, however,
      established that neither of these beta-apo-carotenoids accumulates in P19 cells.
      All-trans-retinoic acid accumulated to high levels in P19 cells. This suggests
      that the uptake and metabolism of beta-apo-carotenoids by some cells does not
      involve the same processes used for retinoids and that these may be cell type
      specific. We also investigated the effects of two beta-apo-carotenoids on 3T3-L1
      adipocyte marker gene expression during adipocyte differentiation. Treatment of
      3T3-L1 adipocytes with either beta-apo-13-carotenone or beta-apo-10'-carotenoic
      acid, which lacks RAR antagonist activity, stimulated adipocyte marker gene
      expression. Neither blocked the inhibitory effects of a relatively large dose of
      exogenous all-trans-retinoic acid on adipocyte differentiation. Our data suggest
      that in addition to acting as transcriptional antagonists, some beta-apo
      carotenoids act through other mechanisms to influence 3T3-L1 adipocyte
      differentiation.

PMID- 25602704
TI  - Imaging and characterizing cells using tomography.
AB  - We can learn much about cell function by imaging and quantifying sub-cellular
      structures, especially if this is done non-destructively without altering said
      structures. Soft X-ray tomography (SXT) is a high-resolution imaging technique
      for visualizing cells and their interior structure in 3D. A tomogram of the cell,
      reconstructed from a series of 2D projection images, can be easily segmented and
      analyzed. SXT has a very high specimen throughput compared to other high
      resolution structure imaging modalities; for example, tomographic data for
      reconstructing an entire eukaryotic cell is acquired in a matter of minutes. SXT
      visualizes cells without the need for chemical fixation, dehydration, or staining
      of the specimen. As a result, the SXT reconstructions are close representations
      of cells in their native state. SXT is applicable to most cell types. The deep
      penetration of soft X-rays allows cells, even mammalian cells, to be imaged
      without being sectioned. Image contrast in SXT is generated by the differential
      attenuation soft X-ray illumination as it passes through the specimen.
      Accordingly, each voxel in the tomographic reconstruction has a measured linear
      absorption coefficient (LAC) value. LAC values are quantitative and give rise to
      each sub-cellular component having a characteristic LAC profile, allowing
      organelles to be identified and segmented from the milieu of other cell contents.
      In this chapter, we describe the fundamentals of SXT imaging and how this
      technique can answer real world questions in the study of the nucleus. We also
      describe the development of correlative methods for the localization of specific
      molecules in a SXT reconstruction. The combination of fluorescence and SXT data
      acquired from the same specimen produces composite 3D images, rich with detailed
      information on the inner workings of cells. 

PMID- 25602705
TI  - Tissue- and sex-specific effects of beta-carotene 15,15' oxygenase (BCO1) on
      retinoid and lipid metabolism in adult and developing mice.
AB  - In mammals, beta-carotene-15,15'-oxygenase (BCO1) is the main enzyme that cleaves
      beta-carotene, the most abundant vitamin A precursor, to generate retinoids
      (vitamin A derivatives), both in adult and developing tissues. We previously
      reported that, in addition to this function, BCO1 can also influence the
      synthesis of retinyl esters, the storage form of retinoids, in the mouse embryo
      at mid-gestation. Indeed, lack of embryonic BCO1 impaired both lecithin-dependent
      and acyl CoA-dependent retinol esterification, mediated by lecithin:retinol
      acyltransferase (LRAT) and acyl CoA:retinol acyltransferase (ARAT), respectively.
      Furthermore, embryonic BCO1 also influenced the ester pools of cholesterol and
      diacylglycerol. In this report, we gained novel insights into this alternative
      function of BCO1 by investigating whether BCO1 influenced embryonic retinoid and
      lipid metabolism in a tissue-dependent manner. To this end, livers and brains
      from wild-type and BCO1-/- embryos at mid-gestation were analyzed for retinoid
      and lipid content, as well as gene expression levels. We also asked whether or
      not the role of BCO1 as a regulator of lecithin- and acyl CoA-dependent retinol
      esterification was exclusively restricted to the developing tissues. Thus, a
      survey of retinol and retinyl ester levels in adult tissues of wild-type, BCO1-/
      , LRAT-/- and LRAT-/-BCO1-/- mice was performed. We showed that the absence of
      BCO1 affects embryonic retinoid and lipid homeostasis in a tissue-specific manner
      and that retinyl ester formation is also influenced by BCO1 in a few adult
      tissues (pancreas, lung, heart and adipose) in a sex-dependent manner.

PMID- 25602708
TI  - Empowering people to be healthier: public health nutrition through the Ottawa
      Charter.
AB  - The WHO's Ottawa Charter highlights five priority areas for taking action in
      public health. Only one of them is at the individual level as action at more
      upstream intervention levels, such as community or policy levels, is critical for
      enabling individuals to succeed. The objective of the present paper is to give
      insight into the many complex processes involved in public health nutrition by
      describing the Ottawa Charter's five priority areas for taking action using
      public health nutrition initiatives I have been involved in. Evidence-based
      guidelines for healthy eating and infant feeding provide an essential basis for
      individuals to 'develop personal skills' (Action Area 1). 'Re-orienting health
      services' (Action Area 2) can address the needs of vulnerable population
      subgroups, such as the culturally sensitive diabetes prevention programme
      established for an Indo-Asian community in Canada. Identifying geographic areas
      at high risk of childhood obesity enables better strategic planning and targeting
      of resources to 'strengthen community action' (Action Area 3). Calorie menu
      labelling can 'create supportive environments' (Action Area 4) through
      encouraging a demand for less energy-dense, healthier food options. 'Building
      healthy public policy' (Action Area 5) to implement mandatory folic acid food
      fortification for prevention of birth defects has many advantages over a
      voluntary approach. In conclusion, evaluation and evidence-based decision-making
      needs to take account of different strategies used to take action in each of
      these priority areas. For this, the randomised control trial needs adaptation to
      determine the best practice in public health nutrition where interventions play
      out in real life with all its confounding factors. 

PMID- 25602707
TI  - Identification of a Serum amyloid A gene and the association of SNPs with Vibrio
      resistance and growth traits in the clam Meretrix meretrix.
AB  - Serum amyloid A (SAA), an acute response protein as well as an apolipoprotein, is
      considered to play crucial roles in both innate immunity and lipid metabolism. In
      this study, a SAA gene (MmSAA) was identified in the clam Meretrix meretrix. The
      full length DNA of MmSAA was 1407bp, consisting of three exons and two introns.
      The distribution of MmSAA in clam tissues was examined with the highest
      expression in hepatopancreas. In response to the Vibrio parahaemolyticus
      challenge, MmSAA mRNA showed significantly higher expression at 24 h post
      challenge in experimental clams (P < 0.05). Forty-eight single nucleotide
      polymorphisms (SNPs) in the DNA partial sequence of MmSAA were discovered and
      examined for their association with Vibrio-resistance and growth traits,
      respectively. The single SNP association analysis indicated that five single SNPs
      (g.42, g.72, g.82, g.147 and g.165) were significantly associated with Vibrio
      resistance (P < 0.05). Haplotype analysis produced additional support for
      association with the Chi-square values 6.393 (P = 0.012). Among the five selected
      SNPs, the effect of a missense mutation (g.82, A -> G) was detected by site
      directed mutagenesis with fusion expression of protein assay, and the result
      showed that the recombinant plasmids containing wild-type pET30a-MmSAA had more
      inhibition effect than the mutant ones on the growth rate of the host bacteria.
      In addition, four growth traits of the clams in 09G3SPSB population were recorded
      and the SNP g.176 was found to be significantly associated with the growth traits
      with the Global score value 0.790 (P = 0.015). Our findings suggested that common
      genetic variation in MmSAA might contribute to the risk of susceptibility to
      Vibrio infection and might be associated with the growth traits in the clams M.
      meretrix, and more works are still needed to validate these SNPs as potential
      markers for actual selective breeding. 

PMID- 25602706
TI  - TDP-43 regulates beta-adducin (Add2) transcript stability.
AB  - TDP-43 is an RNA-binding protein involved in several steps of mRNA metabolism
      including transcription, splicing and stability. It is also involved in ALS and
      FTD, neurodegenerative diseases characterized by TDP-43 nuclear depletion. We
      previously identified TDP-43 as a binder of the downstream element (DSE) of the
      beta-Adducin (Add2) brain-specific polyadenylation site (A4 PAS), suggesting its
      involvement in pre-mRNA 3' end processing. Here, by using chimeric minigenes, we
      showed that TDP-43 depletion in HeLa and HEK293 cells resulted in down-regulation
      of both the chimeric and endogenous Add2 transcripts. Despite having confirmed
      TDP-43-DSE in vitro interaction, we demonstrated that the in vivo effect was not
      mediated by the TDP-43-DSE interaction. In fact, substitution of the Add2 DSE
      with viral E-SV40 and L-SV40 DSEs, which are not TDP-43 targets, still resulted
      in decreased Add2 mRNA levels after TDP-43 downregulation. In addition, we failed
      to show interaction between TDP-43 and key polyadenylation factors, such as CstF
      64 and CPSF160 and excluded TDP-43 involvement in pre-mRNA cleavage and
      regulation of polyA tail length. These evidences allowed us to exclude the pre
      hypothesized role of TDP43 in modulating 3' end processing of Add2 pre-mRNA.
      Finally, we showed that TDP-43 regulates Add2 gene expression levels by
      increasing Add2 mRNA stability. Considering that Add2 in brain participates in
      synapse assembly, synaptic plasticity and their stability, and its genetic
      inactivation in mice leads to LTP, LTD, learning and motor-coordination deficits,
      we hypothesize that a possible loss of Add2 function by TDP-43 depletion may
      contribute to ALS and FTD disease states. 

PMID- 25602709
TI  - Nanoparticle biphasic calcium phosphate loading on gelatin-pectin scaffold for
      improved bone regeneration.
AB  - Biphasic calcium phosphate (BCP) nanoparticles were loaded with porous gelatin
      pectin (GE-P) scaffolds. The biodegradable gelatin-pectin-BCP scaffolds were
      produced as miscible mixtures with well-defined interconnected pores to
      facilitate osteoconductivity and enhance bone formation. It was observed that the
      compressive strength increased with the loading of BCP nanoparticles. From in
      vitro results, cell adhesion, viability, and proliferation were found in the GE-P
      10 scaffolds in comparison with those without BCP, resulting in high alkaline
      phosphate (ALP), and osteopontin (OPN) expression at 21 days. Micro-computed
      tomography data, hematoxylin and eosin staining, and immunohistochemistry (OPN,
      OCN, COL I, and COL II) confirmed rapid new bone formation in rabbit models. Our
      results provide a novel and simple method to provide an adequate scaffold, and
      thus GE-P-BCP porous scaffolds may be appropriate candidates for bone tissue
      engineering. 

PMID- 25602712
TI  - Exploring molecular insights into aggregation of hydrotrope sodium cumene
      sulfonate in aqueous solution: a molecular dynamics simulation study.
AB  - Hydrotropes are an important class of molecules that enhance the solubility of an
      otherwise insoluble or sparingly soluble solute in water. Besides this,
      hydrotropes are also known to self-assemble in aqueous solution and form
      aggregates. It is the hydrotrope aggregate that helps in solubilizing a solute
      molecule in water. In view of this, we try to understand the underlying mechanism
      of self-aggregation of hydrotrope sodium cumene sulfonate (SCS) in water. We have
      carried out classical molecular dynamics simulations of aqueous SCS solutions
      with a regime of concentrations. Moreover, to examine the effect of temperature
      change on SCS aggregation, if any, we consider four different temperatures
      ranging from 298 to 358 K. From the estimation of densities of different
      solutions we calculate apparent and partial molal volumes of the hydrotrope. The
      changes in these quantities increase sharply at a characteristic minimum
      hydrotrope concentration. The determination of molal expansibility at infinite
      dilution for different temperatures indicates the water structure breaking by SCS
      molecules, which is further confirmed by the calculations of water-water pair
      correlation functions. In comparison with typical surfactants in micelles, a
      slightly lower value of volumetric change upon aggregation per carbon atom
      suggests the formation of a more closely packed structure of hydrotrope
      aggregates. A close examination of different structural properties of hydrotrope
      solutions reveals that the hydrophobic interactions through their hydrophobic
      tails significantly contribute in hydrotrope aggregation,and the dehydration of
      hydrophobic tail at elevated temperatures is also visible. Remarkably, the
      aggregates have little or no impact on the average number of water-SCS hydrogen
      bonds. 

PMID- 25602713
TI  - In situ observation of divergent phase transformations in individual sulfide
      nanocrystals.
AB  - Inorganic nanocrystals have attracted widespread attention both for their size
      dependent properties and for their potential use as building blocks in an array
      of applications. A complete understanding of chemical transformations in
      nanocrystals is important for controlling structure, composition, and electronic
      properties. Here, we utilize in situ high-resolution transmission electron
      microscopy to study structural and morphological transformations in individual
      sulfide nanocrystals (copper sulfide, iron sulfide, and cobalt sulfide) as they
      react with lithium. The experiments reveal the influence of structure and
      composition on the transformation pathway (conversion versus displacement
      reactions), and they provide a high-resolution view of the unique displacement
      reaction mechanism in copper sulfide in which copper metal is extruded from the
      crystal. The structural similarity between the initial and final phases, as well
      as the mobility of ions within the crystal, are seen to exert a controlling
      influence on the reaction pathway. 

PMID- 25602710
TI  - Evaluation of the dopamine beta-hydroxylase (DbetaH) inhibitor nepicastat in
      participants who meet criteria for cocaine use disorder.
AB  - In the present study, we tested the hypothesis that the potent and selective
      dopamine-beta-hydroxylase (DbetaH) inhibitor nepicastat would have minimal
      effects on cardiovascular and pharmacokinetic parameters associated with cocaine
      administration and would reduce the positive subjective effects produced by
      cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral
      nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20
      and 40mg) in non-treatment seeking participants who metcriteria for cocaine use
      disorder. Safety analyses revealed that nepicastat was well-tolerated and there
      were no differences in adverse events observed after nepicastat plus cocaine vs.
      cocaine alone. In addition, the pharmacokinetic properties of cocaine
      administration were not altered by nepicastat treatment. Cocaine-induced
      cardiovascular and subjective effects were evaluated for completers in the cohort
      randomized to nepicastat (n=13) using a within-subjects statistical analysis
      strategy. Specifically, the cardiovascular and subjective effects of cocaine were
      assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of
      nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main
      effect of nepicastat to reduce several cocaine-induced positive subjective
      effects. Taken together, these data indicate that nepicastat is safe when co
      administered with cocaine and may suppress its positive subjective effects, and
      may be viable as a pharmacotherapy for treatment of cocaine use disorder. 

PMID- 25602711
TI  - Pain in Canadian Veterans: analysis of data from the Survey on Transition to
      Civilian Life.
AB  - BACKGROUND: Little is known about the prevalence of chronic pain among Veterans
      outside the United States. OBJECTIVE: To describe the prevalence of chronic pain
      and associated sociodemographic, health behaviour, employment/income, disability,
      and physical and mental health factors in Canadian Veterans. METHODS: The 2010
      Survey on Transition to Civilian Life included a nationally representative sample
      of 3154 Canadian Armed Forces Regular Force Veterans released from service
      between 1998 and 2007. Data from a telephone survey of Veterans were linked with
      Department of National Defence and Veterans Affairs Canada administrative
      databases. Pain was defined as constant/reoccurring pain (chronic pain) and as
      moderate/severe pain interference with activities. RESULTS: Forty-one percent of
      the population experienced constant chronic pain and 23% experienced intermittent
      chronic pain. Twenty-five percent reported pain interference. Needing help with
      tasks of daily living, back problems, arthritis, gastrointestinal conditions and
      age >= 30 years were independently associated with chronic pain. Needing help
      with tasks of daily living, back problems, arthritis, mental health conditions,
      age >= 30 years, gastrointestinal conditions, low social support and
      noncommissioned member rank were associated with pain interference. CONCLUSIONS:
      These findings provide evidence for agencies and those supporting the well-being
      of Veterans, and inform longitudinal studies to better understand the
      determinants and life course effects of chronic pain in military Veterans.

PMID- 25602715
TI  - Frailty index predicts severe complications in gynecologic oncology patients.
AB  - OBJECTIVE: The purpose of this study was to quantify the predictive value of
      frailty index on 30-day Clavien class IV (requiring critical care support) and
      class V (30-day mortality) complications after gynecologic cancer surgery.
      METHODS: Patients included in the National Surgical Quality Improvement Program
      (NSQIP) 2008-2011 had a final diagnosis of gynecologic malignancy. Modified
      frailty index (mFI) was calculated with 11 variables. Higher mFI scores indicated
      more severe comorbidities. Logistic regression was used to control for known
      predictors of complications. RESULTS: Of the total 6551 patients, 188 (2.9%) of
      the patients experienced a Clavien IV/V complication. 2958 patients had a score
      of 0 (45.2%), 2405 patients had a score of 1 (36.7%), 985 patients had a score of
      2 (15%), 162 patients had a score of 3 (2.5%) and 41 patients had a score>=4
      (0.6%). The rates of Clavien IV/V complications were 2%, 2.7%, 4.4%, 7.4% and
      24.4% for mFI scores of 0, 1, 2, 3 and >=4, respectively (p<0.001). Variables
      found to be significant for predicting Clavien IV and V complications on logistic
      regression modeling were preoperative albumin<3g/dL (OR=6.5), operative time
      (OR=1.003 per min increase), non-laparoscopic surgery (OR=3.3), and frailty index
      (OR score 0=reference, score 1=1.26, score 2=1.9, score 3=2.33 and
      score>=4=12.5). Taking the two preoperative factors of albumin and mFI allowed
      for greater precision in identifying women who are at higher risk for requiring
      ICU care (>10% risk). CONCLUSIONS: Modified frailty index (mFI) is predictive of
      the need for critical care support and 30-day mortality after surgery for
      gynecologic cancer.

PMID- 25602714
TI  - HER2 over-expressing high grade endometrial cancer expresses high levels of
      p95HER2 variant.
AB  - BACKGROUND: Subsets of high grade endometrial cancer (EnCa) over-express HER2
      (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity
      utilizing trastuzumab, an approved platform for HER2 positive breast cancer
      (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may
      confer resistance. The objective of this investigation was to characterize the
      expression of the p95HER2 truncated variant in EnCa. MATERIALS AND METHODS: With
      institutional approval, 86 high grade EnCa tumors were identified with tumor
      specimens from surgeries performed between 2000 and 2011. Clinical data were
      collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry
      (IHC, HercepTest(r)), HER2 fluorescent in situ hybridization (FISH), along with
      total HER2 (H2T) and p95HER2 assessment with VeraTag(r) testing. Regression
      models were used to compare a cohort of 86 breast tumors selected for equivalent
      HER2 protein expression. RESULTS: We identified 44 high grade endometrioid and 42
      uterine serous carcinomas (USC). IHC identified high HER2 expression (2+ or 3+)
      in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC,
      4 endometrioid). Both HER2 gene amplification and protein expression correlated
      with H2T values. High p95HER2 expression above 2.8RF/mm2 was observed in 53%
      (n=54) with significant correlation with H2T levels. When matched to a cohort of
      107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented
      with higher p95 levels (p<0.001). CONCLUSIONS: These data demonstrate that
      compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly
      providing rationale for the trastuzumab resistance observed in EnCa.

PMID- 25602716
TI  - The missing picture: blindness in giant cell arteritis.

PMID- 25602717
TI  - Chondrodysplasia punctata tibia metacarpal type: report of a 1.5 year old child
      with severe short stature and extensive calcific stippling.

PMID- 25602718
TI  - Distribution of Fasciola hepatica and F. gigantica in the endemic area of Guilan,
      Iran: Relationships between zonal overlap and phenotypic traits.
AB  - Fascioliasis is a zoonotic disease emerging in numerous parts of the world. In
      any endemic area, the characterisation of scenarios and patterns of infection
      must always be considered the starting point before implementing any control
      measure. Fascioliasis is a parasitic disease of different epidemiological,
      pathological and control characteristics depending on the endemic area and the
      causal agent, Fasciola hepatica and Fasciolagigantica. Classically it has been
      accepted that F. hepatica is present worldwide, while the distribution of the two
      species overlaps in many areas of Africa and Asia. Fascioliasis caused by F.
      hepatica, F. gigantica and intermediate forms is present in Guilan province, a
      complicated epidemiological situation where the highest human infection rates
      have been described in Iran. Morphometric tools were used to analyse the possible
      relationship between liver-fluke metric traits and geographical and altitudinal
      distribution. This is the first study in which a detailed distribution of both
      Fasciola species is analysed in a human fascioliasis endemic area with a zonal
      overlap transmission pattern. An accurate analysis was conducted to
      phenotypically discriminate between fasciolids from naturally infected livestock
      (cattle, buffaloes, sheep and goats). The distribution of the % F. hepatica-like
      (F.h.) and F. gigantica-like (F.g.) flukes detected in each liver versus altitude
      (m) in each group was analysed. The presence of F.g. specimens mainly in
      locations below sea level (average: 11.23% F.h., 88.77% F.g.), the presence of
      both species with similar intensity at 1-99m (average: 56.95% F.h., 43.05% F.g.)
      and the presence of F.h. specimens mainly from 100 to 999m (average: 71.69% F.h.,
      28.31% F.g.) as well as in locations with an altitude above 1000m (average:
      97.48% F.h., 2.52% F.g.) are noteworthy. A significant positive correlation was
      obtained between altitude and % F.h., and a significant negative correlation was
      obtained between altitude and % F.g. The results show that F.g. populations in
      cattle, buffaloes and sheep share larger size values, but smaller specimens are
      present mainly in lowland populations located below sea level, independently of
      the host species (cattle, buffalo). F.g. from lowland cattle presented larger
      worm size variability. Four different fascioliasis transmission areas may be
      distinguished in Guilan: (a) lowland coastal areas neighbouring the Caspian Sea
      shore, below sea level, where basically F. gigantica-like specimens are found;
      (b) a coastal plain with an altitude between 1 and 100m where both species co
      exist; (c) areas with altitude values of 100-999m where mainly F. hepatica-like
      specimens are found; (d) highland mountainous areas, where basically F. hepatica
      like specimens are found. The study of the influence of the host species on the
      liver fluke was also carried out by a size-out analysis. This is the first report
      concerning the decisive influence exercised by the host species on the metric
      traits of F. gigantica adults. 

PMID- 25602719
TI  - A meta-analysis of nutrient intake, feed efficiency and performance in cattle
      grazing on tropical grasslands.
AB  - It is essential to quantify the potential of tropical grasslands to allow
      significant feed efficiency for grazing livestock in controlled conditions such
      as at pasture. We conducted a quantitative analysis of published studies
      reporting the experimental results of average daily gains (ADG) and diet
      characteristics obtained specifically under grazing conditions (17 publications
      and 41 experiments), which have been less studied compared with controlled
      conditions in stalls. The database was analyzed to determine the average and
      range of values obtained for ADG (g/kg BW), dry matter digestibility, intake
      (DMI) and digestible DMI (DDMI, g/kg BW) and feed conversion efficiencies (FCE),
      as well as to predict the response of these parameters to the main strategies
      investigated in the literature - that is, mainly the stocking rate (SR) and the
      concentrate intake (CI). The ADG reached 1.2 kg BW per day and was directly
      linked to DDMI (ADG=-1.63+0.42 DDMI -0.0084 DDMI2, n=90, r.m.s.e=0.584, R
      2=0.93). The DDMI, which was representative of the nutrient input, was driven
      mainly by DMI rather than dry matter digestibility, whereas these two parameters
      did not correlate (r=0.068, P=0.56). The average global FCE (0.11 g ADG/g DDMI)
      showed a greater association with the metabolic FCE (0.17 g ADG/g DMI) than the
      digestive FCE (0.62). The CI (g DM/kg BW) increased ADG (ADG=2376+CI 56.1, n=16,
      r.m.s.e.=441, R 2=0.95). The SR expressed as kg BW/ha decreased the individual
      ADG by 1.19 g/kg BW per additional ton of BW/ha, whereas the global ADG
      calculated per ha increased by 0.57 per additional ton BW/ha. When the SR was
      expressed as kg BW/ton DM and per ha rather than as kg BW/ha, the impact on the
      individual ADG decreased by 0.18 or 0.86 g per additional ton BW/ha, depending on
      the initial BW of the cattle. These results provide a better view of the
      potential performance and feeding of cattle in tropical grasslands. The results
      provide an improved quantification of the relationships between diet and
      performance, as well as the overall quantitative impact of SR and
      supplementation. 

PMID- 25602720
TI  - Plants used as food and medicine by Polish migrants in Misiones, Argentina.
AB  - In this article we discuss the importance of food plants, both introduced and
      native, in the pharmacopoeia of the Polish community in Misiones, Argentina. Food
      species constitute a relevant portion of all botanicals used by Polish settlers
      in home therapies (41%), while introduced food species prevail among the
      continued herbal remedies used by the study group. We explain this pattern of use
      by food plant availability, their versatility as reflected in the number of
      medicinal applications, and also their importance in cross-cultural relations.
      Finally, we conclude that several food plants used by Polish migrants (e.g.,
      Allium sativum, Mentha xpiperita, and Camellia sinensis) may have served to
      "strengthen" migrants' identity within the host country. 

PMID- 25602721
TI  - Chemical biologists rush to San Francisco for the ICBS.

PMID- 25602728
TI  - Phospholipids: a neuroinflammation emerging target.

PMID- 25602729
TI  - Noncoding RNA: linking microRNAs to their targets.

PMID- 25602734
TI  - Cell-permeable inhibitors of neuronal nitric oxide synthase open new prospects
      for the treatment of neurological disorders.
AB  - The disubstituted pyrimidines based SAR study by Silverman et al. ( J. Med. Chem.
      2014 , DOI: 10.1021/jm501719e ) was focused on improving bioavailability and
      physicochemical properties of the designed inhibitors while retaining the potency
      for neural nitric oxide synthase (nNOS) and selectivity over the other two nitric
      oxide synthase (NOS) isoforms (endothelial NOS and inducible NOS). One of the new
      promising lead compounds, compound 7, displayed nanomolar potency for nNOS (Ki =
      19 nM), good selectivity over endothelial (260-fold), and inducible (41-fold) NOS
      isoforms and also showed potential for oral bioavailability (good cell
      permeability with efflux ratio of 1.8) and broad safety profile with minimal off
      target activities at 50 CNS based receptors. This remarkable achievement not only
      serves as a template for next generation selective NOS inhibitor design but also
      opens new prospects for the treatment of neurological disorders. 

PMID- 25602735
TI  - Structure-property-composition relationships in doped zinc oxides: enhanced
      photocatalytic activity with rare earth dopants.
AB  - In this paper, we demonstrate the use of continuous hydrothermal flow synthesis
      (CHFS) technology to rapidly produce a library of 56 crystalline (doped) zinc
      oxide nanopowders and two undoped samples, each with different particle
      properties. Each sample was produced in series from the mixing of an aqueous
      stream of basic zinc nitrate (and dopant ion or modifier) solution with a flow of
      superheated water (at 450  degrees C and 24.1 MPa), whereupon a crystalline
      nanoparticle slurry was rapidly formed. Each composition was collected in series,
      cleaned, freeze-dried, and then characterized using analytical methods, including
      powder X-ray diffraction, transmission electron microscopy, Brunauer-Emmett
      Teller surface area measurement, X-ray photoelectron spectroscopy, and UV-vis
      spectrophotometry. Photocatalytic activity of the samples toward the
      decolorization of methylene blue dye was assessed, and the results revealed that
      transition metal dopants tended to reduce the photoactivity while rare earth
      ions, in general, increased the photocatalytic activity. In general, low dopant
      concentrations were more beneficial to having greater photodecolorization in all
      cases. 

PMID- 25602737
TI  - Thermochromic and mechanochromic luminescence umpolung in isostructural metal
      organic frameworks based on Cu6I6 clusters.
AB  - Two isostructural metal-organic framework (MOF) materials, namely,
      {[MeSi((3)Py)3]6(Cu6I6)}n (1) and {[ MeSi((3)Qy)3]6(Cu6I6)}n (2), featuring Cu6I6
      clusters were synthesized from tridentate arylsilane ligands of the type
      MeSi((3)Py)3 ((3)Py = 3-pyridyl) and MeSi((3)Qy)3 ((3)Qy = 3-quinolyl),
      respectively. While the MOF 1 displays the usual thermochromism associated with
      traditional Cu4I4Py4 clusters, the MOF 2 shows (3)XLCT/(3)MLCT emission due to
      the Cu6I6 cluster core at both 298 and 77 K, albeit with some marginal variations
      in its emission wavelengths. Interestingly, an unusual reversal in the
      mechanochromic luminescent behavior was observed for these isostructural MOFs at
      298 K wherein a pronounced blue-shifted high energy emission for 1 (from orange
      to yellowish-orange) and a red-shifted low-energy emission for 2 (from green to
      orange) were obtained upon grinding these samples. This is primarily due to the
      variations in their cuprophilic interactions as 1 displays shorter Cu...Cu
      distances (2.745(1) A) in comparison with those present in 2 (3.148(0) A). As a
      result, the ground sample of 2 exhibits a prominent red shift in luminescence
      owing to the reduction of its Cu...Cu distances to an unknown value closer to the
      sum of van der Waals radii between two Cu(I) atoms (2.80 A). However, the blue
      shifted emission in 1 is presumably attributed to the rise in its lowest
      unoccupied molecular orbital energy levels caused by changes in the secondary
      packing forces. Furthermore, the absorption and emission characteristics of 1 and
      2 were substantiated by time-dependent density functional theory calculations on
      their discrete-model compounds. In addition, the syntheses, reactivity studies,
      and photophysical properties of two one-dimensional MOFs, namely,
      {[MeSi((3)Qy)3]2(Cu2I2)}n (3) and {[MeSi((3)Qy)3](CuI)}n (4), having dimeric
      Cu2I2 and monomeric CuI moieties, respectively, were examined. 

PMID- 25602736
TI  - Does 5HTTLPR Genotype Moderate the Association of Family Environment With Child
      Attention-Deficit Hyperactivity Disorder Symptomatology?
AB  - Problematic family dynamics are common among youth with attention-deficit
      hyperactivity disorder (ADHD). Multiple mechanisms, including diathesis-stress
      (vulnerability) and differential susceptibility Gene * Environment interaction
      effects (G * E), have been proposed to account for this association. G * E
      effects for ADHD were examined via interactions between a genetic marker
      hypothesized to influence sensitivity to the environment (the promoter
      polymorphism of the serotonin transporter gene -5HTTLPR) and family conflict and
      cohesion in predicting ADHD symptoms. There were 498 youth ages 6-17 years (251
      ADHD, 213 non-ADHD) and their parents who completed a multistage, multi-informant
      assessment (including parent and youth reports on the Family Environment Scale),
      and saliva sample collection for genotyping. Linear regression analyses examined
      interactions between 5HTTLPR genotype and the Family Environment Scale scales of
      conflict and cohesion reported by parent and child. Criteria laid out by Roisman
      et al. ( 2012 ) were applied to evaluate diathesis stress versus differential
      susceptibility G * E mechanisms. Results demonstrated interactions between
      5HTTLPR genotype and both conflict and cohesion in predicting inattention but not
      hyperactivity-impulsivity. Both interactions were highly consistent with
      differential susceptibility models of G * E effects. 5HTTLPR genotype appeared to
      moderate the relationship between family conflict/cohesion and inattentive
      symptoms. Interactions highlight the role of 5HTTLPR genotype as a potential
      marker of environmental sensitivity and provide support for differential
      susceptibility models of G * E effects for ADHD. 

PMID- 25602738
TI  - Interaction of a patterned amphiphilic polyphenylene dendrimer with a lipid
      monolayer: electrostatic interactions dominate.
AB  - Dendrimeric macromolecules with defined shape and size are promising candidates
      for delivering drug or DNA molecules into cells. In this work we study the
      influence of an amphiphilic polyphenylene dendrimer on a model cell membrane
      consisting of a condensed 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)
      lipid monolayer. A small surface pressure decrease is observed when the dendrimer
      solution is injected into the aqueous phase below the monolayer. X-ray
      reflectivity measurements show that the surface monolayer remains intact. The
      molecular-scale picture is obtained with sum-frequency generation spectroscopy.
      With this technique, we observe that the tails of the surfactant molecules become
      less ordered upon interaction with the amphiphilic polyphenylene dendrimer. In
      contrast, the water molecules below the DPPC layer become more ordered. Our
      observations suggest that electrostatic interactions between the negative charge
      of the dendrimer and the positively charged part of the DPPC headgroup keep the
      dendrimer located below the headgroup. No evidence of dendrimer insertion into
      the membrane has been observed. Apparently before entering the cell membrane the
      dendrimer can stick at the hydrophilic part of the lipids. 

PMID- 25602740
TI  - Candida albicans OPI1 regulates filamentous growth and virulence in vaginal
      infections, but not inositol biosynthesis.
AB  - ScOpi1p is a well-characterized transcriptional repressor and master regulator of
      inositol and phospholipid biosynthetic genes in the baker's yeast Saccharomyces
      cerevisiae. An ortholog has been shown to perform a similar function in the
      pathogenic fungus Candida glabrata, but with the distinction that CgOpi1p is
      essential for growth in this organism. However, in the more distantly related
      yeast Yarrowia lipolytica, the OPI1 homolog was not found to regulate inositol
      biosynthesis, but alkane oxidation. In Candida albicans, the most common cause of
      human candidiasis, its Opi1p homolog, CaOpi1p, has been shown to complement a S.
      cerevisiae opi1? mutant for inositol biosynthesis regulation when heterologously
      expressed, suggesting it might serve a similar role in this pathogen. This was
      tested in the pathogen directly in this report by disrupting the OPI1 homolog and
      examining its phenotypes. It was discovered that the OPI1 homolog does not
      regulate INO1 expression in C. albicans, but it does control SAP2 expression in
      response to bovine serum albumin containing media. Meanwhile, we found that
      CaOpi1 represses filamentous growth at lower temperatures (30  degrees C) on
      agar, but not in liquid media. Although, the mutant does not affect virulence in
      a mouse model of systemic infection, it does affect virulence in a rat model of
      vaginitis. This may be because Opi1p regulates expression of the SAP2 protease,
      which is required for rat vaginal infections.

PMID- 25602742
TI  - Vibrational and electronic structure of the alpha- and beta-naphthyl radicals via
      slow photoelectron velocity-map imaging.
AB  - Slow photoelectron velocity-map imaging (SEVI) spectroscopy has been used to
      study the vibronic structure of gas-phase alpha- and beta-naphthyl radicals
      (C(10)H(7)). SEVI of cryogenically cooled anions yields spectra with <4 cm(-1)
      resolution, allowing for the observation and interpretation of congested
      vibrational structure. Isomer-specific photoelectron spectra of detachment to the
      radical ground electronic states show detailed structure, allowing assignment of
      vibrational fundamental frequencies. Transitions to the first excited states of
      both radical isomers are also observed; vibronic coupling and photodetachment
      threshold effects are considered to explain the structure of the excited bands.

PMID- 25602741
TI  - Carbon nanotube membrane stack for flow-through sequential regenerative electro
      Fenton.
AB  - Electro-Fenton is a promising advanced oxidation process for water treatment
      consisting a series redox reactions. Here, we design and examine an
      electrochemical filter for sequential electro-Fenton reactions to optimize the
      treatment process. The carbon nanotube (CNT) membrane stack (thickness ~ 200 MUm)
      used here consisted of 1) a CNT network cathode for O2 reduction to H2O2, 2) a
      CNT-COOFe(2+) cathode to chemical reduction H2O2 to (*)OH and HO(-) and to
      regenerate Fe(2+) in situ, 3) a porous PVDF or PTFE insulating separator, and 4)
      a CNT filter anode for remaining intermediate oxidation intermediates. The
      sequential electro-Fenton was compared to individual electrochemical and Fenton
      process using oxalate, a persistent organic, as a target molecule. Synergism is
      observed during the sequential electro-Fenton process. For example, when [DO]in =
      38 +/- 1 mg L(-1), J = 1.6 mL min(-1), neutral pH, and Ecell = 2.89 V, the
      sequential electro-Fenton oxidation rate was 206.8 +/- 6.3 mgC m(-2) h(-1), which
      is 4-fold greater than the sum of the individual electrochemistry (16.4 +/- 3.2
      mgC m(-2) h(-1)) and Fenton (33.3 +/- 1.3 mgC m(-2) h(-1)) reaction fluxes, and
      the energy consumption was 45.8 kWh kgTOC(-1). The sequential electro-Fenton was
      also challenged with the refractory trifluoroacetic acid (TFA) and
      trichloroacetic acid (TCA), and they can be transferred at a removal rate of 11.3
      +/- 1.2 and 21.8 +/- 1.9 mmol m(-2) h(-1), respectively, with different
      transformation mechanisms.

PMID- 25602743
TI  - Foliar bacterial communities of trembling aspen in a common garden.
AB  - Microbial associations with plants are widely distributed and are structured by a
      number of biotic and physical factors. Among biotic factors, the host plant
      genotype may be integral to these plant-microbe interactions. Trees in the genus
      Populus have become models for studies in scaling effects of host plant genetics
      and in plant-microbe interactions. Using 454 pyrosequencing of the 16S rRNA gene,
      we assessed the foliar bacterial community of 7 genotypes of mature trembling
      aspen trees (Populus tremuloides Michx.) grown in a common garden. Trees were
      selected based on prior analyses showing clonal variation in their concentration
      of chemicals conferring resistance against insect herbivores. At broad taxonomic
      designations, the bacterial community of trembling aspen was similar across all
      plant genotypes. At a finer taxonomic scale, the foliage of these trees varied in
      their community composition, but there was no distinct pattern to colonization or
      abundance related to plant genotype. The most abundant operational taxonomic
      units (OTUs) were classified as Ralstonia, Bradyrhizobium, Pseudomonas, and
      Brucella. These OTUs varied across the common garden, but there was no
      significant effect of host plant genotype or spatial position on the abundance of
      these members. Our results suggest that aspen genotype is less important in the
      structuring of its foliar bacterial communities than are other, poorly understood
      processes. 

PMID- 25602744
TI  - Effect of diabetes mellitus on giant cell arteritis.
AB  - BACKGROUND: To determine if Type 2 diabetes mellitus (DM) is protective against
      giant cell arteritis (GCA) and to estimate the incidence of GCA diagnosis from
      Medicare claims. METHODS: Medicare 5% claims files from 1991 to 2011 were used to
      identify beneficiaries diagnosed with DM, but not GCA, within a 3-year
      ascertainment period. Propensity score matching was used to define a control
      group of nondiabetics with comparable demographic covariates. Competing risk
      regression was then used to assess the impact of DM diagnosis on GCA diagnosis.
      To allow for a 3-year ascertainment period, the analysis sample was limited to
      beneficiaries older than 68 years at baseline. RESULTS: A total of 151,041
      beneficiaries diagnosed with DM were matched to an equal number of controls. Mean
      study follow-up was 67.75 months. GCA was diagnosed among 1116 beneficiaries with
      DM (0.73%) vs 465 (0.30%) controls. The risk of receiving a GCA diagnosis among
      patients with DM was increased by 100% (subhazard ratio, 2.00; 95% confidence
      interval, 1.78-2.25). The annual incidence of GCA diagnosis among claims for US
      Medicare beneficiaries older than 68 years old was 93 in 100,000. CONCLUSIONS: A
      DM diagnosis is not protective against a GCA diagnosis in the Medicare
      population. Our data suggest that a DM diagnosis increases the risk of GCA
      diagnosis within 5.7 years for Medicare beneficiaries older than 68 years.

PMID- 25602745
TI  - Smad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and
      positively relates to better clinical outcome in human hepatocellular carcinoma.
AB  - Transforming growth factor beta (TGF-beta) is cytostatic towards damage-induced
      compensatory hepatocyte proliferation. This function is frequently lost during
      hepatocarcinogenesis, thereby switching the TGF-beta role from tumour suppressor
      to tumour promoter. In the present study, we investigate Smad7 overexpression as
      a pathophysiological mechanism for cytostatic TGF-beta inhibition in liver damage
      and hepatocellular carcinoma (HCC). Transgenic hepatocyte-specific Smad7
      overexpression in damaged liver of fumarylacetoacetate hydrolase (FAH)-deficient
      mice increased compensatory proliferation of hepatocytes. Similarly, modulation
      of Smad7 expression changed the sensitivity of Huh7, FLC-4, HLE and HLF HCC cell
      lines for cytostatic TGF-beta effects. In our cohort of 140 HCC patients, Smad7
      transcripts were elevated in 41.4% of HCC samples as compared with adjacent
      tissue, with significant positive correlation to tumour size, whereas low Smad7
      expression levels were significantly associated with worse clinical outcome.
      Univariate and multivariate analyses indicate Smad7 levels as an independent
      predictor for overall (P<0.001) and disease-free survival (P=0.0123). Delineating
      a mechanism for Smad7 transcriptional regulation in HCC, we identified cold-shock
      Y-box protein-1 (YB-1), a multifunctional transcription factor. YB-1 RNAi reduced
      TGF-beta-induced and endogenous Smad7 expression in Huh7 and FLC-4 cells
      respectively. YB-1 and Smad7 mRNA expression levels correlated positively
      (P<0.0001). Furthermore, nuclear co-localization of Smad7 and YB-1 proteins was
      present in cancer cells of those patients. In summary, the present study provides
      a YB-1/Smad7-mediated mechanism that interferes with anti-proliferative/tumour
      suppressive TGF-beta actions in a subgroup of HCC cells that may facilitate
      aspects of tumour progression. 

PMID- 25602746
TI  - Assessment of the effect of trichostatin A on HeLa cells through FT-IR
      spectroscopy.
AB  - Trichostatin A (TSA) is one of histone deacetylase (HDAC) inhibitor drugs which
      can suppress the enzymatic activity of deacytylases and promote the acetylation
      of both histone and nonhistone proteins in cells. Investigation of the effect of
      TSA on cellular acetylation is critical for better understanding of the antitumor
      drug's mechanism interacting with cancer cells. As Fourier transform infrared
      spectroscopy (FT-IR) is a powerful analytical tool which can detect
      nondestructively and quantitatively biological samples without biotagging and
      biolabeling, here we employed FT-IR spectroscopy to probe the chemical and
      structural changes of proteins in the TSA treated cells, and with the aid of
      fluorescent microscopy, we could scrutinize the time-dependent and dose effects
      on the acetylation level promoted by TSA. Our results showed that TSA caused an
      elevated level of cellular acetylation and conformational/structural changes of
      proteins in the cells, and a higher dosage of TSA caused a higher percent of
      alpha-helix structure accompanied by an increment of acetylation level in both
      histones and cytoskeleton proteins. This work therefore not only validates the
      usefulness of FT-IR spectroscopy in the quantitative assessment of cellular
      acetylation but also may open an avenue to the in-depth investigation of the
      effect of HDAC inhibitor drugs such as TSA on cancer cells. 

PMID- 25602747
TI  - [Epidemiology of sexting].
AB  - AIM: Aim of the present study was to assess the prevalence of sexting, defined as
      "the sharing of images or videos of sexually explicit content", identifying the
      age groups involved and assessing the possible cultural ties. The study also
      aimed at providing a clear picture of the phenomenon to educators and parents, an
      essential starting point for planning any effective educational program. METHODS:
      We performed a literature search on Medline (PubMed) database. In addition, the
      2011 and 2012 surveys released by Eurispes and Telefono Azzurro were also
      consulted. "Google Trends" application provided additional details. RESULTS: In
      Italy teenagers from 12 to 18 years who received sexually oriented material
      increased from 10.2% in 2011 to 25.9% in 2012. In the USA 69.4% declared having
      received sexually oriented material, while 66.7% reported having sent it. In
      Italy, 1 out of 10 teenagers (age range 16-18) found himself in danger for having
      posted his nude photos online. CONCLUSION: The practice of sexting involves a
      wide age range with different legal implications. Teenagers practice sexting to
      attract attention and prove to be involved in a relationship. Sexting usually
      does not have any consequence but in rare cases, about 4%, malicious behavior
      such as sexting for money, to tease or take someone under threat has been
      reported. Moreover, during the past decade the cases of online harassment
      increased, especially involving young women. Only by closely monitoring the
      phenomenon and studying its deeper motivations it could be possible to plan
      effective educational programs, integrating sexting and the correct use of new
      media into a structured sexual education project.

PMID- 25602748
TI  - Relative frequency of norovirus infection in children with acute gastroenteritis.
AB  - AIM: The aim of this study was to determine the prevalence of norovirus among
      children with acute gastroenteritis in 2009 and 2010. We also aimed that, to
      detecting the possible clinical and laboratory differences among cases in 2009
      and 2010. METHODS: Fecal samples were collected from children under 16 years of
      age who were admitted for acute gastroenteritis. Norovirus was detected using
      immunochromatography. For the comparison of seasonal distribution, clinical
      manifestations, and laboratory results between cases, we divided subjects into
      two groups by year. RESULTS: Norovirus infection was detected in 112 of the 1027
      collected samples (10.9%). In three cases with norovirus, other enteric viruses
      like rotavirus and adenovirus are detected concurrently, and these were excluded.
      After the exclusion of three cases with co-infections, statistical analysis was
      made in 109 cases. Most of the positive cases were between 1-24 months of age
      (N.=75, 67%). The rate of norovirus infection peaked in winter in 2010 (P<0.05).
      However, the rates were not significantly different between seasons in 2009
      (P>0.05). We did not detect any positive cases in late summer and autumn in 2010.
      Diarrhea (97.2%), vomiting (95.4%), and abdominal pain (65.1%) were most
      frequently encountered symptoms of patients with norovirus. Leukocytosis and
      neutrophilia were significantly higher in 2010 than 2009 (P<0.05). CONCLUSION:
      The prevalence and clinical characteristics of norovirus in our study group is
      similar but seasonal distribution is different between two years. Most of the
      cases were <24 months of age. Like rotavirus, norovirus vaccine can be developed
      to prevent infection.

PMID- 25602749
TI  - [Differences in sports participation for children and adolescents with solitary
      kidney due to renal tumors across Europe. Time for harmonization].
AB  - As a result of advances in treatment, almost 90% of children diagnosed with Wilms
      tumor became long-term survivors, and have a sustainable quality of life. These
      patients' involvement in sports during their childhood is hopefully increasing
      too. The cornerstone of renal tumor cure remains radical nephrectomy, however, so
      survivors live with a solitary kidney. In most European countries and the USA,
      the involvement in sports of children with a solitary kidney depends on a
      responsible physician saying a "qualified yes", pending individual assessment.
      Unlike the case in the rest of Europe, in Italy having only one kidney
      automatically disqualifies an individual wishing to participate in any organized
      "competitive" sports carrying some risk of renal trauma, including basketball,
      soccer and sometime volleyball. This absolute restriction is based on ad hoc
      Ministerial rulings concerning "Health protection in sport activities". But
      available data do not seem to support such an absolute limitation on
      participation in sports based exclusively on the fact of having a single kidney.
      The sport-specific incidence of kidney injuries has been estimated at 2.3
      injuries per million male athlete/exposures for basketball (2.5 for females), and
      2.6 for soccer (6.0 for girls). Kidney injuries are significantly more rare than
      head or spine injuries. This article aims to provide Italian sport medicine
      specialists and policy-makers with the necessary background so that the current,
      over-protective "unquestionably no" response can be reconsidered, and converted
      into a still well-founded, more permissive attitude to the sports activities
      suitable for any children with a solitary normal kidney. 

PMID- 25602750
TI  - Mirror movements in patients with hemiplegic cerebral palsy and porencephaly:
      when one hand becomes two hands.

PMID- 25602751
TI  - Engineering of human bone with Plexur MTM in acetabular roof reconstruction after
      curettage of a giant aggressive aneurismal bone cyst of the left emypelvis.

PMID- 25602752
TI  - Afebrile convulsion: a rare complication of inactivated hepatitis A vaccine in
      childhood.

PMID- 25602753
TI  - Anxious and egocentric: how specific emotions influence perspective taking.
AB  - People frequently feel anxious. Although prior research has extensively studied
      how feeling anxious shapes intrapsychic aspects of cognition, much less is known
      about how anxiety affects interpersonal aspects of cognition. Here, we examine
      the influence of incidental experiences of anxiety on perceptual and conceptual
      forms of perspective taking. Compared with participants experiencing other
      negative, high-arousal emotions (i.e., anger or disgust) or neutral feelings,
      anxious participants displayed greater egocentrism in their mental-state
      reasoning: They were more likely to describe an object using their own spatial
      perspective, had more difficulty resisting egocentric interference when
      identifying an object from others' spatial perspectives, and relied more heavily
      on privileged knowledge when inferring others' beliefs. Using both experimental
      causal-chain and measurement-of-mediation approaches, we found that these effects
      were explained, in part, by uncertainty appraisal tendencies. Further supporting
      the role of uncertainty, a positive emotion associated with uncertainty (i.e.,
      surprise) produced increases in egocentrism that were similar to anxiety.
      Collectively, the results suggest that incidentally experiencing emotions
      associated with uncertainty increase reliance on one's own egocentric perspective
      when reasoning about the mental states of others.

PMID- 25602754
TI  - Emotional arousal and discount rate in intertemporal choice are reference
      dependent.
AB  - Many decisions involve weighing immediate gratification against future
      consequences. In such intertemporal choices, people often choose smaller,
      immediate rewards over larger delayed rewards. It has been proposed that
      emotional responses to immediate rewards lead us to choose them at our long-term
      expense. Here we utilize an objective measure of emotional arousal-pupil dilation
      to examine the role of emotion in these decisions. We show that emotional arousal
      responses, as well as choices, in intertemporal choice tasks are reference
      dependent and reflect the decision-maker's recent history of offers. Arousal
      increases when less predictable rewards are better than expected, whether those
      rewards are immediate or delayed. Furthermore, when immediate rewards are less
      predictable than delayed rewards, participants tend to be patient. When delayed
      rewards are less predictable, immediate rewards are preferred. Our findings
      suggest that we can encourage people to be more patient by changing the context
      in which intertemporal choices are made.

PMID- 25602755
TI  - Role of hexokinase-1 in the survival of HIV-1-infected macrophages.
AB  - Viruses have developed various strategies to protect infected cells from
      apoptosis. HIV-1 infected macrophages are long-lived and considered reservoirs
      for HIV-1. One significant deciding factor between cell survival and cell death
      is glucose metabolism. We hypothesized that HIV-1 protects infected macrophages
      from apoptosis in part by modulating the host glycolytic pathway specifically by
      regulating hexokinase-1 (HK-1) an enzyme that converts glucose to glucose-6
      phosphate. Therefore, we analyzed the regulation of HK-1 in HIV-1 infected PBMCs,
      and in a chronically HIV-1 infected monocyte-like cell line, U1. Our results
      demonstrate that HIV-1 induces a robust increase in HK-1 expression.
      Surprisingly, hexokinase enzymatic activity was significantly inhibited in HIV-1
      infected PBMCs and in PMA differentiated U1 cells. Interestingly, we observed
      increased levels of mitochondria-bound HK-1 in PMA induced U1 cells and in the
      HIV-1 accessory protein, viral protein R (Vpr) transduced U937 cell derived
      macrophages. Dissociation of HK-1 from mitochondria in U1 cells using a
      pharmacological agent, clotrimazole (CTZ) induced mitochondrial membrane
      depolarization and caspase-3/7 mediated apoptosis. Dissociation of HK-1 from
      mitochondria in Vpr transduced U937 also activated caspase-3/7 activity. These
      observations indicate that HK-1 plays a non-metabolic role in HIV-1 infected
      macrophages by binding to mitochondria thereby maintaining mitochondrial
      integrity. These results suggest that targeting the interaction of HK-1 with the
      mitochondria to induce apoptosis in persistently infected macrophages may prove
      beneficial in purging the macrophage HIV reservoir. 

PMID- 25602758
TI  - FastGCN: a GPU accelerated tool for fast gene co-expression networks.
AB  - Gene co-expression networks comprise one type of valuable biological networks.
      Many methods and tools have been published to construct gene co-expression
      networks; however, most of these tools and methods are inconvenient and time
      consuming for large datasets. We have developed a user-friendly, accelerated and
      optimized tool for constructing gene co-expression networks that can fully
      harness the parallel nature of GPU (Graphic Processing Unit) architectures.
      Genetic entropies were exploited to filter out genes with no or small expression
      changes in the raw data preprocessing step. Pearson correlation coefficients were
      then calculated. After that, we normalized these coefficients and employed the
      False Discovery Rate to control the multiple tests. At last, modules
      identification was conducted to construct the co-expression networks. All of
      these calculations were implemented on a GPU. We also compressed the coefficient
      matrix to save space. We compared the performance of the GPU implementation with
      those of multi-core CPU implementations with 16 CPU threads, single-thread C/C++
      implementation and single-thread R implementation. Our results show that GPU
      implementation largely outperforms single-thread C/C++ implementation and single
      thread R implementation, and GPU implementation outperforms multi-core CPU
      implementation when the number of genes increases. With the test dataset
      containing 16,000 genes and 590 individuals, we can achieve greater than 63 times
      the speed using a GPU implementation compared with a single-thread R
      implementation when 50 percent of genes were filtered out and about 80 times the
      speed when no genes were filtered out.

PMID- 25602757
TI  - Dose-dependent effects of a soluble dietary fibre (pectin) on food intake,
      adiposity, gut hypertrophy and gut satiety hormone secretion in rats.
AB  - Soluble fermentable dietary fibre elicits gut adaptations, increases satiety and
      potentially offers a natural sustainable means of body weight regulation. Here we
      aimed to quantify physiological responses to graded intakes of a specific dietary
      fibre (pectin) in an animal model. Four isocaloric semi-purified diets containing
      0, 3.3%, 6.7% or 10% w/w apple pectin were offered ad libitum for 8 or 28 days to
      young adult male rats (n = 8/group). Measurements were made of voluntary food
      intake, body weight, initial and final body composition by magnetic resonance
      imaging, final gut regional weights and histology, and final plasma satiety
      hormone concentrations. In both 8- and 28-day cohorts, dietary pectin inclusion
      rate was negatively correlated with food intake, body weight gain and the change
      in body fat mass, with no effect on lean mass gain. In both cohorts, pectin had
      no effect on stomach weight but pectin inclusion rate was positively correlated
      with weights and lengths of small intestine and caecum, jejunum villus height and
      crypt depth, ileum crypt depth, and plasma total glucagon-like peptide-1 (GLP-1)
      and peptide tyrosine tyrosine (PYY) concentrations, and at 8 days was correlated
      with weight and length of colon and with caecal mucosal depth. Therefore, the
      gut's morphological and endocrine adaptations were dose-dependent, occurred
      within 8 days and were largely sustained for 28 days during continued dietary
      intervention. Increasing amounts of the soluble fermentable fibre pectin in the
      diet proportionately decreased food intake, body weight gain and body fat
      content, associated with proportionately increased satiety hormones GLP-1 and PYY
      and intestinal hypertrophy, supporting a role for soluble dietary fibre-induced
      satiety in healthy body weight regulation. 

PMID- 25602756
TI  - Cell necrosis-independent sustained mitochondrial and nuclear DNA release
      following trauma surgery.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA), a potent proinflammatory damage-associated
      molecular pattern, is released in large titers following trauma. The effect of
      trauma surgery on mtDNA concentration is unknown. We hypothesized that mtDNA and
      nuclear DNA (nDNA) levels would increase proportionately with the magnitude of
      surgery and both would then decrease rapidly. METHODS: In this prospective pilot,
      plasma was sampled from 35 trauma patients requiring orthopedic surgical
      intervention at six perioperative time points. Healthy control subjects (n = 20)
      were sampled. DNA was extracted, and the mtDNA and nDNA were assessed using
      quantitative polymerase chain reaction. Markers of cell necrosis were also
      assayed (creatine kinase, lactate dehydrogenase, and aspartate aminotransferase).
      RESULTS: The free plasma mtDNA and nDNA levels (ng/mL) were increased in trauma
      patients compared with healthy controls at all time points (mtDNA: preoperative
      period, 108 [46-284]; postoperative period, 96 [29-200]; 7 hours postoperatively,
      88 [43-178]; 24 hours, 79 [36-172]; 3 days, 136 [65-263]; 5 days, 166 [101-434]
      [healthy controls, 11 (5-19)]) (nDNA: preoperative period, 52 [25-130];
      postoperative period, 100 [35-208]; 7 hours postoperatively, 75 [36-139]; 24
      hours postoperatively, 85 [47-133]; 3 days, 79 [48-117]; 5 days, 99 [41-154]
      [healthy controls, 29 (16-54)]). Elevated DNA levels did not correlate with
      markers of cellular necrosis. mtDNA was significantly elevated compared with nDNA
      at preoperative period (p = 0.003), 3 days (p = 0.003), and 5 days (p = 0.0014).
      Preoperative mtDNA levels were greater with shorter time from injury to surgery
      (p = 0.0085). Postoperative mtDNA level negatively correlated with intraoperative
      crystalloid infusion (p = 0.0017). Major pelvic surgery (vs. minor) was
      associated with greater mtDNA release 5 days postoperatively (p < 0.05).
      CONCLUSION: This pilot of heterogeneous orthopedic trauma patients showed that
      the release of mtDNA and nDNA is sustained for 5 days following orthopedic trauma
      surgery. Postoperative, circulating DNA is not associated with markers of tissue
      necrosis but is associated with surgical invasiveness and is inversely related to
      intraoperative fluid administration. Sustained elevation of mtDNA levels could be
      of inflammatory origin and may contribute to postinjury dysfunctional
      inflammation. LEVEL OF EVIDENCE: Prospective study, level III.

PMID- 25602759
TI  - Reconstructing genome-wide protein-protein interaction networks using multiple
      strategies with homologous mapping.
AB  - BACKGROUND: One of the crucial steps toward understanding the biological
      functions of a cellular system is to investigate protein-protein interaction
      (PPI) networks. As an increasing number of reliable PPIs become available, there
      is a growing need for discovering PPIs to reconstruct PPI networks of interesting
      organisms. Some interolog-based methods and homologous PPI families have been
      proposed for predicting PPIs from the known PPIs of source organisms. RESULTS:
      Here, we propose a multiple-strategy scoring method to identify reliable PPIs for
      reconstructing the mouse PPI network from two well-known organisms: human and
      fly. We firstly identified the PPI candidates of target organisms based on
      homologous PPIs, sharing significant sequence similarities (joint E-value <= 1 *
      10(-40)), from source organisms using generalized interolog mapping. These PPI
      candidates were evaluated by our multiple-strategy scoring method, combining
      sequence similarities, normalized ranks, and conservation scores across multiple
      organisms. According to 106,825 PPI candidates in yeast derived from human and
      fly, our scoring method can achieve high prediction accuracy and outperform
      generalized interolog mapping. Experiment results show that our multiple-strategy
      score can avoid the influence of the protein family size and length to
      significantly improve PPI prediction accuracy and reflect the biological
      functions. In addition, the top-ranked and conserved PPIs are often
      orthologous/essential interactions and share the functional similarity. Based on
      these reliable predicted PPIs, we reconstructed a comprehensive mouse PPI
      network, which is a scale-free network and can reflect the biological functions
      and high connectivity of 292 KEGG modules, including 216 pathways and 76
      structural complexes. CONCLUSIONS: Experimental results show that our scoring
      method can improve the predicting accuracy based on the normalized rank and
      evolutionary conservation from multiple organisms. Our predicted PPIs share
      similar biological processes and cellular components, and the reconstructed
      genome-wide PPI network can reflect network topology and modularity. We believe
      that our method is useful for inferring reliable PPIs and reconstructing a
      comprehensive PPI network of an interesting organism.

PMID- 25602760
TI  - Longitudinal stability in reading comprehension is largely heritable from grades
      1 to 6.
AB  - Reading comprehension is a foundational academic skill and significant attention
      has focused on reading development. This report is the first to examine the
      stability and change in genetic and environmental influences on reading
      comprehension across Grades 1 to 6. This developmental range is particularly
      important because it encompasses the timespan in which most children move from
      learning how to read to using reading for learning. Longitudinal simplex models
      were fitted separately for two independent twin samples (N = 706; N = 976).
      Results suggested that the shared environment contributed to variance in early
      but not later reading. Instead, stability in reading development was largely
      mediated by continuous genetic influences. Thus, although reading is clearly a
      learned skill and the environment remains important for reading development,
      individual differences in reading comprehension appear to be also influenced by a
      core of genetic stability that persists through the developmental course of
      reading. 

PMID- 25602762
TI  - Design and synthesis of potent and multifunctional aldose reductase inhibitors
      based on quinoxalinones.
AB  - Quinoxalin-2(1H)-one based design and synthesis produced several series of aldose
      reductase (ALR2) inhibitor candidates. In particular, phenolic structure was
      installed in the compounds for the combination of antioxidant activity and
      strengthening the ability to fight against diabetic complications. Most of the
      series 6 showed potent and selective effects on ALR2 inhibition with IC50 values
      in the range of 0.032-0.468 MUM, and 2-(3-(2,4-dihydroxyphenyl)-7-fluoro-2
      oxoquinoxalin-1(2H)-yl)acetic acid (6e) was the most active. More significantly,
      most of the series 8 revealed not only good activity in the ALR2 inhibition but
      also potent antioxidant activity, and 2-(3-(3-methoxy-4-hydroxystyryl)-2
      oxoquinoxalin-1(2H)-yl)acetic acid (8d) was even as strong as the well-known
      antioxidant Trolox at a concentration of 100 MUM, verifying the C3 p
      hydroxystyryl side chain as the key structure for alleviating oxidative stress.
      These results therefore suggest an achievement of multifunctional ALR2 inhibitors
      having both potency for ALR2 inhibition and as antioxidants. 

PMID- 25602764
TI  - Plasmonic control of radiative properties of semiconductor quantum dots coupled
      to plasmonic ring cavities.
AB  - In recent years, a lot of effort has been made to achieve controlled delivery of
      target particles to the hotspots of plasmonic nanoantennas, in order to probe
      and/or exploit the extremely large field enhancements produced by such
      structures. While in many cases such high fields are advantageous, there are
      instances where they should be avoided. In this work, we consider the
      implications of using the standard nanoantenna geometries when colloidal quantum
      dots are employed as target entities. We show that in this case, and for various
      reasons, dimer antennas are not the optimum choice. Plasmonic ring cavities are a
      better option despite low field enhancements, as they allow collective coupling
      of many quantum dots in a reproducible and predictable manner. In cases where
      larger field enhancements are required, or for larger quantum dots, nonconcentric
      ring-disk cavities can be employed instead. 

PMID- 25602761
TI  - Family Caregiver's Perception of Alzheimer's disease and caregiving in Chinese
      culture.
AB  - This study examined the perception of Alzheimer's disease (AD) and caregiving
      among family caregivers of individuals with mild cognitive impairment (MCI) and
      AD in China. In-depth semistructured interviews were conducted with 46 family
      caregivers of individuals with cognitive impairment in 2009 in Wuhan and Beijing,
      China. Participants included 38 spouses, 7 adult children, and 1 sibling, aged
      between 41 and 85 years old. The findings showed that all family caregivers
      thought the Chinese terminology of AD laonian chidai, brought discrimination to
      individuals with cognitive impairment. Caregivers of individuals with AD
      experienced burden and desired an increase of formal services. Traditional
      beliefs of respecting elders and caring for extended family members were held
      among family caregivers of individuals with cognitive impairment, and there was
      nearly no difference found between caregivers of AD and those of MCI. It implied
      that traditional culture provided positive influences on caring for elders with
      cognitive impairment. An alternative term for MCI may contribute to further
      reducing the discrimination brought by the old Chinese terminology of AD laonian
      chidai. Development of formal services for elders with cognitive impairment may
      contribute to reducing caregivers' worries about future caregiving. 

PMID- 25602765
TI  - Convergent strategy for the regioselective synthesis of nonaggregated alpha
      triaryl-beta-carboxy zinc phthalocyanines.
AB  - A new design of nonaggregated zinc(II) carboxyphthalocyanines with potential
      application in dye-sensitized solar cells has been developed. It is based on the
      introduction of bulky and rigid aryl groups at three alpha positions of the
      macrocycle. The synthesis has been carried out following a convergent route in
      which the bulky aryl groups are introduced by a Suzuki-Miyaura cross-coupling
      reaction on a preformed triiodophthalocyanine derivative. Two regioisomers of
      this alpha-triaryl-beta-carboxyphthalocyanine could be isolated by column
      chromatography. 

PMID- 25602766
TI  - Two-trace model for spike-timing-dependent synaptic plasticity.
AB  - We present an effective model for timing-dependent synaptic plasticity (STDP) in
      terms of two interacting traces, corresponding to the fraction of activated NMDA
      receptors and the [Formula: see text] concentration in the dendritic spine of the
      postsynaptic neuron. This model intends to bridge the worlds of existing
      simplistic phenomenological rules and highly detailed models, thus constituting a
      practical tool for the study of the interplay of neural activity and synaptic
      plasticity in extended spiking neural networks. For isolated pairs of pre- and
      postsynaptic spikes, the standard pairwise STDP rule is reproduced, with
      appropriate parameters determining the respective weights and timescales for the
      causal and the anticausal contributions. The model contains otherwise only three
      free parameters, which can be adjusted to reproduce triplet nonlinearities in
      hippocampal culture and cortical slices. We also investigate the transition from
      time-dependent to rate-dependent plasticity occurring for both correlated and
      uncorrelated spike patterns. 

PMID- 25602767
TI  - Structural intervention distance for evaluating causal graphs.
AB  - Causal inference relies on the structure of a graph, often a directed acyclic
      graph (DAG). Different graphs may result in different causal inference statements
      and different intervention distributions. To quantify such differences, we
      propose a (pre-)metric between DAGs, the structural intervention distance (SID).
      The SID is based on a graphical criterion only and quantifies the closeness
      between two DAGs in terms of their corresponding causal inference statements. It
      is therefore well suited for evaluating graphs that are used for computing
      interventions. Instead of DAGs, it is also possible to compare CPDAGs, completed
      partially DAGs that represent Markov equivalence classes. The SID differs
      significantly from the widely used structural Hamming distance and therefore
      constitutes a valuable additional measure. We discuss properties of this distance
      and provide a (reasonably) efficient implementation with software code available
      on the first author's home page. 

PMID- 25602768
TI  - On firing rate estimation for dependent interspike intervals.
AB  - If interspike intervals are dependent, the instantaneous firing rate does not
      catch important features of spike trains. In this case, the conditional
      instantaneous rate plays the role of the instantaneous firing rate for the case
      of samples of independent interspike intervals. If the conditional distribution
      of the interspikes intervals (ISIs) is unknown, it becomes difficult to evaluate
      the conditional firing rate. We propose a nonparametric estimator for the
      conditional instantaneous firing rate for Markov, stationary, and ergodic ISIs.
      An algorithm to check the reliability of the proposed estimator is introduced,
      and its consistency properties are proved. The method is applied to data obtained
      from a stochastic two-compartment model and to in vitro experimental data. 

PMID- 25602769
TI  - Memristor models for machine learning.
AB  - In the quest for alternatives to traditional complementary metal-oxide
      semiconductor, it is being suggested that digital computing efficiency and power
      can be improved by matching the precision to the application. Many applications
      do not need the high precision that is being used today. In particular, large
      gains in area and power efficiency could be achieved by dedicated analog
      realizations of approximate computing engines. In this work we explore the use of
      memristor networks for analog approximate computation, based on a machine
      learning framework called reservoir computing. Most experimental investigations
      on the dynamics of memristors focus on their nonvolatile behavior. Hence, the
      volatility that is present in the developed technologies is usually unwanted and
      is not included in simulation models. In contrast, in reservoir computing,
      volatility is not only desirable but necessary. Therefore, in this work, we
      propose two different ways to incorporate it into memristor simulation models.
      The first is an extension of Strukov's model, and the second is an equivalent
      Wiener model approximation. We analyze and compare the dynamical properties of
      these models and discuss their implications for the memory and the nonlinear
      processing capacity of memristor networks. Our results indicate that device
      variability, increasingly causing problems in traditional computer design, is an
      asset in the context of reservoir computing. We conclude that although both
      models could lead to useful memristor-based reservoir computing systems, their
      computational performance will differ. Therefore, experimental modeling research
      is required for the development of accurate volatile memristor models. 

PMID- 25602770
TI  - Range-based ICA using a nonsmooth quasi-newton optimizer for
      electroencephalographic source localization in focal epilepsy.
AB  - Independent component analysis (ICA) aims at separating a multivariate signal
      into independent nongaussian signals by optimizing a contrast function with no
      knowledge on the mixing mechanism. Despite the availability of a constellation of
      contrast functions, a Hartley-entropy-based ICA contrast endowed with the
      discriminacy property makes it an appealing choice as it guarantees the absence
      of mixing local optima. Fueled by an outstanding source separation performance of
      this contrast function in practical instances, a succession of optimization
      techniques has recently been adopted to solve the ICA problem. Nevertheless, the
      nondifferentiability of the considered contrast restricts the choice of the
      optimizer to the class of derivative-free methods. On the contrary, this letter
      concerns a Riemannian quasi-Newton scheme involving an explicit expression for
      the gradient to optimize the contrast function that is differentiable almost
      everywhere. Furthermore, the inexact line search insisting on the weak Wolfe
      condition and a terminating criterion befitting the partly smooth function
      optimization have been generalized to manifold settings, leaving the previous
      results intact. The investigations with diversified images and the
      electroencephalographic (EEG) data acquired from 45 focal epileptic subjects
      demonstrate the efficacy of our approach in terms of computational savings and
      reliable EEG source localization, respectively. Additional experimental results
      are available in the online supplement. 

PMID- 25602771
TI  - A study on the optimal double parameters for steepest descent with momentum.
AB  - This letter presents the stability analysis for two steepest descent algorithms
      with momentum for quadratic functions. The corresponding local optimal parameters
      in Torii and Hagan ( 2002 ) and Zhang ( 2013 ) are extended to the global optimal
      parameters, that is, both the optimal learning rates and the optimal momentum
      factors are obtained simultaneously which make for the fastest convergence. 

PMID- 25602772
TI  - Oscillator-interference models of path integration do not require theta
      oscillations.
AB  - Navigation and path integration in rodents seems to involve place cells, grid
      cells, and theta oscillations (4-12 Hz) in the local field potential. Two main
      theories have been proposed to explain the neurological underpinnings of how
      these phenomena relate to navigation and to each other. Attractor network (AN)
      models revolve around the idea that local excitation and long-range inhibition
      connectivity can spontaneously generate grid-cell-like activity patterns.
      Oscillator interference (OI) models propose that spatial patterns of activity are
      caused by the interference patterns between neural oscillators. In rats, these
      oscillators have a frequency close to the theta frequency. Recent studies have
      shown that bats do not exhibit a theta cycle when they crawl, and yet they still
      have grid cells. This has been interpreted as a criticism of OI models. However,
      OI models do not require theta oscillations. We explain why the absence of theta
      oscillations does not contradict OI models and discuss how the two families of
      models might be distinguished experimentally. 

PMID- 25602773
TI  - Spontaneous motion on two-dimensional continuous attractors.
AB  - Attractor models are simplified models used to describe the dynamics of firing
      rate profiles of a pool of neurons. The firing rate profile, or the neuronal
      activity, is thought to carry information. Continuous attractor neural networks
      (CANNs) describe the neural processing of continuous information such as object
      position, object orientation, and direction of object motion. Recently it was
      found that in one-dimensional CANNs, short-term synaptic depression can
      destabilize bump-shaped neuronal attractor activity profiles. In this article, we
      study two-dimensional CANNs with short-term synaptic depression and spike
      frequency adaptation. We found that the dynamics of CANNs with short-term
      synaptic depression and CANNs with spike frequency adaptation are qualitatively
      similar. We also found that in both kinds of CANNs, the perturbative approach can
      be used to predict phase diagrams, dynamical variables, and speed of spontaneous
      motion. 

PMID- 25602774
TI  - On resolving simultaneous congruences using belief propagation.
AB  - Graphical models and related algorithmic tools such as belief propagation have
      proven to be useful tools in (approximately) solving combinatorial optimization
      problems across many application domains. A particularly combinatorially
      challenging problem is that of determining solutions to a set of simultaneous
      congruences. Specifically, a continuous source is encoded into multiple residues
      with respect to distinct moduli, and the goal is to recover the source
      efficiently from noisy measurements of these residues. This problem is of
      interest in multiple disciplines, including neural codes, decentralized
      compression in sensor networks, and distributed consensus in information and
      social networks. This letter reformulates the recovery problem as an optimization
      over binary latent variables. Then we present a belief propagation algorithm, a
      layered variant of affinity propagation, to solve the problem. The underlying
      encoding structure of multiple congruences naturally results in a layered
      graphical model for the problem, over which the algorithms are deployed,
      resulting in a layered affinity propagation (LAP) solution. First, the
      convergence of LAP to an approximation of the maximum likelihood (ML) estimate is
      shown. Second, numerical simulations show that LAP converges within a few
      iterations and that the mean square error of LAP approaches that of the ML
      estimation at high signal-to-noise ratios. 

PMID- 25602775
TI  - What can neuromorphic event-driven precise timing add to spike-based pattern
      recognition?
AB  - This letter introduces a study to precisely measure what an increase in spike
      timing precision can add to spike-driven pattern recognition algorithms. The
      concept of generating spikes from images by converting gray levels into spike
      timings is currently at the basis of almost every spike-based modeling of
      biological visual systems. The use of images naturally leads to generating
      incorrect artificial and redundant spike timings and, more important, also
      contradicts biological findings indicating that visual processing is massively
      parallel, asynchronous with high temporal resolution. A new concept for acquiring
      visual information through pixel-individual asynchronous level-crossing sampling
      has been proposed in a recent generation of asynchronous neuromorphic visual
      sensors. Unlike conventional cameras, these sensors acquire data not at fixed
      points in time for the entire array but at fixed amplitude changes of their
      input, resulting optimally sparse in space and time-pixel individually and
      precisely timed only if new, (previously unknown) information is available (event
      based). This letter uses the high temporal resolution spiking output of
      neuromorphic event-based visual sensors to show that lowering time precision
      degrades performance on several recognition tasks specifically when reaching the
      conventional range of machine vision acquisition frequencies (30-60 Hz). The use
      of information theory to characterize separability between classes for each
      temporal resolution shows that high temporal acquisition provides up to 70% more
      information that conventional spikes generated from frame-based acquisition as
      used in standard artificial vision, thus drastically increasing the separability
      between classes of objects. Experiments on real data show that the amount of
      information loss is correlated with temporal precision. Our information-theoretic
      study highlights the potentials of neuromorphic asynchronous visual sensors for
      both practical applications and theoretical investigations. Moreover, it suggests
      that representing visual information as a precise sequence of spike times as
      reported in the retina offers considerable advantages for neuro-inspired visual
      computations. 

PMID- 25602776
TI  - Spontaneous action potentials and neural coding in unmyelinated axons.
AB  - The voltage-gated Na and K channels in neurons are responsible for action
      potential generation. Because ion channels open and close in a stochastic
      fashion, spontaneous (ectopic) action potentials can result even in the absence
      of stimulation. While spontaneous action potentials have been studied in detail
      in single-compartment models, studies on spatially extended processes have been
      limited. The simulations and analysis presented here show that spontaneous rate
      in unmyelinated axon depends nonmonotonically on the length of the axon, that the
      spontaneous activity has sub-Poisson statistics, and that neural coding can be
      hampered by the spontaneous spikes by reducing the probability of transmitting
      the first spike in a train. 

PMID- 25602777
TI  - Delay differential analysis of time series.
AB  - Nonlinear dynamical system analysis based on embedding theory has been used for
      modeling and prediction, but it also has applications to signal detection and
      classification of time series. An embedding creates a multidimensional
      geometrical object from a single time series. Traditionally either delay or
      derivative embeddings have been used. The delay embedding is composed of delayed
      versions of the signal, and the derivative embedding is composed of successive
      derivatives of the signal. The delay embedding has been extended to nonuniform
      embeddings to take multiple timescales into account. Both embeddings provide
      information on the underlying dynamical system without having direct access to
      all the system variables. Delay differential analysis is based on functional
      embeddings, a combination of the derivative embedding with nonuniform delay
      embeddings. Small delay differential equation (DDE) models that best represent
      relevant dynamic features of time series data are selected from a pool of
      candidate models for detection or classification. We show that the properties of
      DDEs support spectral analysis in the time domain where nonlinear correlation
      functions are used to detect frequencies, frequency and phase couplings, and
      bispectra. These can be efficiently computed with short time windows and are
      robust to noise. For frequency analysis, this framework is a multivariate
      extension of discrete Fourier transform (DFT), and for higher-order spectra, it
      is a linear and multivariate alternative to multidimensional fast Fourier
      transform of multidimensional correlations. This method can be applied to short
      or sparse time series and can be extended to cross-trial and cross-channel
      spectra if multiple short data segments of the same experiment are available.
      Together, this time-domain toolbox provides higher temporal resolution, increased
      frequency and phase coupling information, and it allows an easy and
      straightforward implementation of higher-order spectra across time compared with
      frequency-based methods such as the DFT and cross-spectral analysis. 

PMID- 25602778
TI  - MRI-based strain and strain rate analysis of left ventricle: a modified
      hierarchical transformation model.
AB  - BACKGROUND: Different from other indicators of cardiac function, such as ejection
      fraction and transmitral early diastolic velocity, myocardial strain is promising
      to capture subtle alterations that result from early diseases of the myocardium.
      In order to extract the left ventricle (LV) myocardial strain and strain rate
      from cardiac cine-MRI, a modified hierarchical transformation model was proposed.
      METHODS: A hierarchical transformation model including the global and local LV
      deformations was employed to analyze the strain and strain rate of the left
      ventricle by cine-MRI image registration. The endocardial and epicardial contour
      information was introduced to enhance the registration accuracy by combining the
      original hierarchical algorithm with an Iterative Closest Points using Invariant
      Features algorithm. The hierarchical model was validated by a normal volunteer
      first and then applied to two clinical cases (i.e., the normal volunteer and a
      diabetic patient) to evaluate their respective function. RESULTS: Based on the
      two clinical cases, by comparing the displacement fields of two selected
      landmarks in the normal volunteer, the proposed method showed a better
      performance than the original or unmodified model. Meanwhile, the comparison of
      the radial strain between the volunteer and patient demonstrated their apparent
      functional difference. CONCLUSIONS: The present method could be used to estimate
      the LV myocardial strain and strain rate during a cardiac cycle and thus to
      quantify the analysis of the LV motion function.

PMID- 25602779
TI  - Noninvasive diagnosis and therapeutic effect evaluation of deep vein thrombosis
      in clinics by near-infrared spectroscopy.
AB  - Deep vein thrombosis (DVT) has become a severe disease with a rising incidence
      rate. The conventional diagnosis relies on complicated imaging modalities that
      may also involve invasive contrast agent injection and ionizing procedures (e.g.,
      venography). Noninvasive near-infrared spectroscopy (NIRS) methods have been
      explored which required the DVT patients to follow some exercise protocols. Here,
      we attempt to use portable NIRS under patients' natural state for DVT diagnosis.
      Nine DVT patients and seven healthy subjects participated in NIRS measurements of
      concentration of oxy- and deoxy-hemoglobins (Delta[HbO2] and Delta[Hb]) relative
      to data on a tissue mimicking phantom at six particular sites of calves. It was
      found that Delta[HbO2] is significantly lower in DVT patients than healthy ones,
      whereas Delta[Hb] is distinctly higher. Moreover, after thrombolytic therapy,
      both Delta[HbO2] and Delta[Hb] in DVT calves assume a gradual convergence to the
      curves of healthy ones. This reveals the potential of NIRS for the noninvasive,
      continuous, and straightforward monitoring/therapeutic effect evaluation of DVT
      in clinics with appropriate bedside monitoring capability.

PMID- 25602780
TI  - Temperature-controlled in vivo ocular exposure to 1090-nm radiation suggests that
      near-infrared radiation cataract is thermally induced.
AB  - The damage mechanism for near-infrared radiation (IRR) induced cataract is
      unclear. Both a photochemical and a thermal mechanism were suggested. The current
      paper aims to elucidate a photochemical effect based on investigation of
      irradiance-exposure time reciprocity. Groups of 20 rats were unilaterally exposed
      to 96-W/cm(2) IRR at 1090 nm within the dilated pupil accumulating 57, 103, 198,
      and 344 kJ/cm(2), respectively. Temperature was recorded at the limbus of the
      exposed eye. Seven days after exposure, the lenses were macroscopically imaged
      and light scattering was quantitatively measured. The average maximum temperature
      increases for exposure times of 10, 18, 33, and 60 min were expressed as 7.0 +/-
      1.1, 6.8 +/- 1.1, 7.6 +/- 1.3, and 7.4 +/- 1.1  degrees C [CI (0.95)] at the
      limbus of the exposed eye. The difference of light scattering in the lenses
      between exposed and contralateral not-exposed eyes was 0.00 +/- 0.02, 0.01 +/-
      0.03, -0.01 +/- 0.02, and -0.01 +/- 0.03 transformed equivalent diazepam
      concentration (tEDC), respectively, and no apparent morphological changes in the
      lens were observed. An exposure to 96-W/cm(2) 1090-nm IRR projected on the cornea
      within the dilated pupil accumulating radiant exposures up to 344 kJ/cm(2) does
      not induce cataract if the temperature rise at the limbus is <8  degrees C. This
      is consistent with a thermal damage mechanism for IRR-induced cataract.

PMID- 25602781
TI  - Intrapulpal temperature changes during root surface irradiation with dual
      wavelength laser (2780 and 940 nm): in vitro study.
AB  - This work reports that the ablation volume and rate of porcine skin changed
      significantly with the change of skin water content. Under the same laser
      irradiation conditions (532 nm Nd:YAG laser, pulse width = 11.5 ns, pulse energy
      = 1.54 J, beam radius = 0.54 mm), the ablation volume dropped by a factor of 4 as
      the skin water content decreased from 40 wt. % (native) to 19 wt. % with a change
      in the ablation rate below and above around 25 wt. %. Based on the ablation
      characteristics observed by in situ shadowgraph images and the calculated tissue
      temperatures, it is considered that an explosive rupture by rapid volumetric
      vaporization of water is responsible for the ablation of the high water content
      of skin, whereas thermal disintegration of directly irradiated surface layer is
      responsible for the low water content of skin.

PMID- 25602782
TI  - Tadalafil, a Phosphodiesterase Inhibitor Protects Stem Cells over Longer Period
      Against Hypoxia/Reoxygenation Injury Through STAT3/PKG-I Signaling.
AB  - Pharmacological preconditioning (PC) with tadalafil, a PDE5A inhibitor, enhances
      protein kinase G-1 (PKG-I) activity, resulting in stem cell survival. Protection
      by PC had two different phases, early (2 h) and late (24 h). However, the
      mechanism of protection during these phases remained grossly unknown. Mesenchymal
      stem cells (MSCs) from adult male Fischer-344 rats were cultured and pretreated
      with tadalafil (100 MUM) for an hour and subjected to 2 h of hypoxia (1% O2),
      followed by reoxygenation (HR: in vitro model mimicking ischemia/reperfusion). We
      observed (i) increased MSC survival with reduced cell cytotoxicity as revealed by
      low lactate dehydrogenase release and trypan blue staining, respectively, in
      tadalafil-treated cells upon HR; (ii) decrease in TUNEL positivity as well as
      caspase activity; (iii) an increase in pAkt/Akt, iNOS, eNOS, and
      pGSK3beta/GSK3beta during the early protection phase of PC, and this protection
      seemed to be a spontaneous adaptive response of MSCs against HR and was
      independent of tadalafil, whereas an increase in Bcl2/Bax was tadalafil
      dependent; and (iv) during the late phase, we observed phosphorylation of STAT3
      at serine727, leading to its entry inside the nucleus and binding onto the
      promoter of PKG-I by three-fold (P<0.05). In conclusion, an increase in Bcl2/Bax
      during the early phase and transcriptional upregulation of PKG-I by STAT3 during
      the late phase were responsible for stem cell protection by tadalafil against
      ischemic injury. 

PMID- 25602785
TI  - Test of an hypothesized structural model of the relationships between cognitive
      style and social anxiety: a 12-month prospective study.
AB  - The aim of this study was to test whether social looming cognitive style accounts
      for the predictive association between early maladaptive schema domains and
      social anxiety. We predicted that early maladaptive schema domains would predict
      the increase of social anxiety over time and that social looming would act as a
      mediator between schema domains and social anxiety. A three-wave longitudinal
      design was used. The participants (N=471, 56.95% women) were Spanish adolescents
      and young adults aged between 16 and 25 years old (Mage=17.81, SD age=3.19). The
      results showed that three schema domains (impaired autonomy and performance,
      impaired limits, and other-directedness) predicted the increase in social anxiety
      and that LCS for social threat acted as a mediator between other-directedness and
      social anxiety at T3. These results are important to improve the knowledge of the
      cognitive mechanisms that are involved in the occurrence and development of
      social anxiety.

PMID- 25602784
TI  - Executive functions and social cognition in highly lethal self-injuring patients
      with borderline personality disorder.
AB  - Risk for potentially lethal self-injurious behavior in borderline personality
      disorder (BPD) may be associated with deficits in neuropsychological functions
      and social cognition. In particular, individuals with BPD engaging in more
      medically damaging self-injurious behaviors may have more severe executive
      function deficits and altered emotion perception as compared to patients engaging
      in less lethal acts. In the current study, 58 patients with BPD reporting a
      lifetime history of self-injurious behavior were administered neuropsychological
      measures of response inhibition, planning and problem-solving,and tests of facial
      emotion recognition and discrimination. Patients who engaged in more medically
      lethal self-injurious behaviors reported engaging in impulsive behaviors more
      frequently and displayed neuropsychological deficits in problem-solving and
      response inhibition. They were also less accurate in recognizing happy facial
      expressions and in discerning subtle differences in emotional intensity in sad
      facial expressions. These findings suggest that patients with BPD that engage in
      more physically damaging self-injurious behaviors may have greater difficulties
      with behavioral control and employ less efficient problem-solving strategies.
      Problems in facial emotion recognition and discrimination may contribute to
      interpersonal difficulties in patients with BPD who self-injure.

PMID- 25602783
TI  - Methionine sulfoxide reductase A negatively controls microglia-mediated
      neuroinflammation via inhibiting ROS/MAPKs/NF-kappaB signaling pathways through a
      catalytic antioxidant function.
AB  - AIMS: Oxidative burst is one of the earliest biochemical events in the
      inflammatory activation of microglia. Here, we investigated the potential role of
      methionine sulfoxide reductase A (MsrA), a key antioxidant enzyme, in the control
      of microglia-mediated neuroinflammation. RESULTS: MsrA was detected in rat
      microglia and its expression was upregulated on microglial activation. Silencing
      of MsrA exacerbated lipopolysaccharide (LPS)-induced activation of microglia and
      the production of inflammatory markers, indicating that MsrA may function as an
      endogenous protective mechanism for limiting uncontrolled neuroinflammation.
      Application of exogenous MsrA by transducing Tat-rMsrA fusion protein into
      microglia attenuated LPS-induced neuroinflammatory events, which was indicated by
      an increased Iba1 (a specific microglial marker) expression and the secretion of
      pro-inflammatory cytokines, and this attenuation was accompanied by inhibiting
      multiple signaling pathways such as p38 and ERK mitogen-activated protein kinases
      (MAPKs) and nuclear factor kappaB (NF-kappaB). These effects were due to MsrA
      mediated reactive oxygen species (ROS) elimination, which may be derived from a
      catalytic effect of MsrA on the reaction of methionine with ROS. Furthermore, the
      transduction of Tat-rMsrA fusion protein suppressed the activation of microglia
      and the expression of pro-inflammatory factors in a rat model of
      neuroinflammation in vivo. INNOVATION: This study provides the first direct
      evidence for the biological significance of MsrA in microglia-mediated
      neuroinflammation. CONCLUSION: Our data provide a profound insight into the role
      of endogenous antioxidative defense systems such as MsrA in the control of
      microglial function.

PMID- 25602787
TI  - Changes in antimicrobial susceptibility profile and prevalence of quinolone low
      sensitive strains in subgingival plaque from acute periodontal lesions after
      systemic administration of sitafloxacin.
AB  - This study aimed to assess changes in antimicrobial susceptibilities of
      subgingival bacteria in acute periodontal lesions following systemic
      administration of a new-generation fluoroquinolone, sitafloxacin and to monitor
      the occurrence and fate of quinolone low-sensitive strains. Patients with acute
      phase of chronic periodontitis were subjected to microbiological assessment of
      their subgingival plaque samples at baseline (A1). Sitafloxacin was then
      administered systemically (100 mg/day for 5 days). The microbiological
      examinations were repeated one week after administration (A2). Susceptibilities
      of clinical isolates from acute sites to various antimicrobials were determined
      using broth and agar dilution methods. At A2, subgingival bacteria with low
      sensitivity to levofloxacin were identified in four patients, and they were
      subjected to a follow-up microbiological examination at on the average 12 months
      after sitafloxacin administration (A3). The patients received initial and
      supportive periodontal therapy during the period A2 to A3. From the examined
      subgingival sites, 8 and 19 clinical isolates were obtained at A2 and A3,
      respectively. Some Streptococcus strains isolated at A2 were found to be
      resistant to levofloxacin (MIC 16-64 MUg/ml), azithromycin (MIC 2->128 MUg/ml) or
      clarithromycin (MIC 1->32 MUg/ml). At A3, isolated streptococci were highly
      susceptible to levofloxacin (MIC 0.5-2 MUg/ml), while those resistant to
      azithromycin or clarithromycin were still isolated. It is suggested that the
      presence of the quinolone low-sensitive strains in initially acute lesions after
      sitafloxacin administration was transient, and they do not persist in the
      subgingival milieu during the periodontal therapy.

PMID- 25602788
TI  - Chlorella ethanol extract induced phase II enzyme through NFE2L2 (nuclear factor
      [erythroid-derived] 2-like 2, NRF2) activation and protected ethanol-induced
      hepatoxicity.
AB  - In this study, we investigated the hepatoprotective effects of ethanol extracts
      from Chlorella vulgaris (CH) on animals. We measured its effect on the quinone
      reductase (QR) activity in Hepa1c1c7 cells, finding that CH induced a
      significantly higher QR activity in these cells. We isolated the active fraction
      (CH F4-2) from CH using chromatography methods. CH F4-2 may activate cellular
      antioxidant enzymes through upregulation of the Nrf2 pathway in hepatocarcinoma
      cells with CH F4-2 (25.0-200 MUg/mL) for 48 h. Furthermore, CH F4-2 increased the
      expression of NQO1 [ NAD(P)H: quinone oxidoreductase, also known as QR], heme
      oxygenase-1, and glutathione-S-transferase P. Moreover, we found that ethanol
      induced hepatic pathological changes-elevations in glutamic oxaloacetic
      transaminase, glutamic pyruvic transaminase, gamma-glutamyltransferase, and
      lactate dehydrogenase-were significantly decreased. The inhibitory effect of CH
      on alcohol-induced liver injury was associated with the suppression of alcohol
      induced increases in intestinal permeability. The ethanol extract from CH was
      found to induce QR activation, making it a potentially good candidate for a
      hepatoprotection agent.

PMID- 25602790
TI  - Quantification of human epidermal growth factor receptor 2 immunohistochemistry
      using the Ventana Image Analysis System: correlation with gene amplification by
      fluorescence in situ hybridization: the importance of instrument validation for
      achieving high (>95%) concordance rate.
AB  - The use of computer-based image analysis for scoring human epidermal growth
      factor receptor 2 (HER2) immunohistochemistry (IHC) has gained a lot of interest
      recently. We investigated the performance of the Ventana Image Analysis System
      (VIAS) in HER2 quantification by IHC and its correlation with fluorescence in
      situ hybridization (FISH). We specifically compared the 3+ IHC results using the
      manufacturer's machine score cutoffs versus laboratory-defined cutoffs with the
      FISH assay. Using the manufacturer's 3+ cutoff (VIAS score; 2.51 to 3.5), 181/536
      (33.7%) were scored 3+, and FISH was positive in 147/181 (81.2%), 2 (1.1%) were
      equivocal, and 32 (17.6%) were FISH (-). Using the laboratory-defined 3+ cutoff
      (VIAS score 3.5), 52 (28.7%) cases were downgraded to 2+, of which 29 (55.7%)
      were FISH (-), and 23 (44.2%) were FISH (+). With the revised cutoff, there were
      improvements in the concordance rate from 89.1% to 97.0% and in the positive
      predictive value from 82.1% to 97.6%. The false-positive rate for 3+ decreased
      from 9.0% to 0.8%. Six of 175 (3.4%) IHC (-) cases were FISH (+). Three cases
      with a VIAS score 3.5 showed polysomy of chromosome 17. In conclusion, the VIAS
      may be a valuable tool for assisting pathologists in HER2 scoring; however, the
      positive cutoff defined by the manufacturer is associated with a high false
      positive rate. This study highlights the importance of instrument
      validation/calibration to reduce false-positive results. 

PMID- 25602789
TI  - Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis.
AB  - Globular hepatic amyloid (GHA) is rare, and its clinical significance remains
      unclear. Recently, leukocyte chemotactic factor-associated amyloidosis (ALECT2)
      has been reported to involve the liver, showing a globular pattern. We reviewed
      70 consecutive cases of hepatic amyloidosis to determine the prevalence and
      morphology of hepatic amyloid subtypes, especially ALECT2 and its association
      with GHA. Each case was reviewed for amyloid subtype (immunohistochemistry and/or
      mass spectrometry), its pattern (linear or globular), and distribution (vascular,
      perisinusoidal, or stromal). In addition, 24 cases of confirmed hepatic ALECT2 on
      mass spectrometry from our consultation files were also reviewed. LECT2
      immunostaining was performed in 49 cases. Of the 70 cases, immunoglobulin light
      chain (AL) type was most common with 41 cases (59%), followed by transthyretin
      (ATTR) 15 cases (22%), 3 cases each of fibrinogen A (AFib) (4%), serum amyloid A
      (AA) (4%), and ALECT2 (4%), 2 cases of apolipoproteins (AApoA1) (3%), and 3 cases
      (4%) were unclassified. Three of our 70 cases (4%), with ALECT2, and all 24 cases
      (100%) of mass spectrometry-confirmed hepatic ALECT2 showed only GHA deposits in
      the hepatic sinusoids and portal tracts. Three (4%) other cases of AL type showed
      a focal globular pattern admixed with prominent linear amyloid. None of the other
      amyloid subtypes showed GHA. LECT2 immunostain was positive in all 27 cases
      (100%) of ALECT2 and negative in the other 22 non-ALECT2 cases (100%) (14 AL, 5
      ATTR, 1 AA, 1 AFib, 1 AApoA1). Pure GHA is uncommon (4%) but is highly specific
      for ALECT2, and LECT2 immunostain is helpful in confirming this amyloid type. 

PMID- 25602791
TI  - Risk stratification by p16 immunostaining of CIN1 biopsies: a retrospective study
      of patients from the quadrivalent HPV vaccine trials.
AB  - Previous studies of p16 immunohistochemistry (IHC) on CIN1 have suggested the
      likely utility of p16 in stratification of women at risk for subsequent CIN2/3.
      But those studies had limitations in statistical power, histologic diagnosis, and
      disease ascertainment. We conducted a retrospective study of p16 IHC on
      adjudicated CIN1 tissue diagnosed in young women participating in the placebo arm
      of the quadrivalent human papillomavirus (HPV) vaccine trials. Tissue sections
      were stained with p16 IHC and hematoxylin and eosin. p16 IHC was scored using
      LAST criteria, and hematoxylin and eosin-stained sections were reviewed for
      concordance with the adjudicated diagnosis. p16 IHC, antecedent high-grade
      cytology, review diagnosis, and HPV16 detection were assessed as independent risk
      factors for subsequent CIN2/3. Five hundred twenty-four patients with CIN1
      biopsies and complete data were identified, 63 (12.0%) of whom developed CIN2/3
      in follow-up. p16 positivity (P=0.06), review diagnosis of CIN2/3 (P=0.04), HPV16
      positivity (P=0.01), and antecedent high-grade cytology (P=0.02) were
      (marginally) associated with CIN2/3. In a logistic regression model, the
      associations with CIN2/3 (vs. other), expressed as odds ratios (95% confidence
      intervals), were 1.6 (0.91-2.8) for p16, 2.0 (1.0-3.7) for HPV16, and 2.2 (1.1
      2.4) for antecedent high-grade cytology. The mean risks for CIN2/3 estimated from
      the model ranged from 7.6% for negative for all markers to 36.3% for positive for
      all 3 markers. p16 IHC does not risk stratify CIN1 patients in a manner that
      would alter recommended management for CIN1. This reinforces the LAST
      recommendations that p16 should only be used selectively for problematic
      scenarios, such as CIN2 because of its inherent lack of reproducibility, cases in
      which one is struggling between CIN1 and CIN2, and benign mimics of CIN3.

PMID- 25602793
TI  - Sporadic microsatellite instability-high colon cancers rarely display
      immunohistochemical evidence of Wnt signaling activation.
AB  - Most sporadic colonic adenocarcinomas are microsatellite stable (MSS) and arise
      from conventional adenomas by dysregulation of the APC/beta-catenin/Wnt signaling
      pathway. Sporadic adenocarcinomas with a high degree of microsatellite
      instability (MSI) likely arise from sessile serrated polyps through the serrated
      neoplastic pathway. These polyps contain BRAF mutations and are prone to
      epigenetic methylation that ultimately silences MLH1, leading to MSI and
      heralding progression of dysplasia to invasive adenocarcinoma. Most investigators
      believe that these 2 models of cancer progression are mutually exclusive,
      although recent studies describe Wnt signaling activation in serrated polyps and
      propose that it plays a role in the development of sporadic colonic
      adenocarcinomas with MSI. We sought to test this hypothesis by evaluating beta
      catenin immunoexpression in 44 sporadic microsatellite unstable adenocarcinomas
      and 44 MSS colon cancers. We defined sporadic MSI-high carcinomas as those with
      loss of MLH1 and PMS2 immunostaining and BRAF V600E mutations that occurred in
      patients 50 years of age or older without a family history of colonic
      adenocarcinoma or Lynch syndrome. Forty-one (93%) of these carcinomas displayed
      membranous beta-catenin staining only, compared with 28 (64%) site-matched MSS
      tumors with abnormal nuclear beta-catenin staining. 

PMID- 25602792
TI  - Molecular and immunohistochemical characterization reveals novel BRAF mutations
      in metanephric adenoma.
AB  - Metanephric adenoma (MA) is a rare benign renal tumor comprised of a neoplastic
      proliferation of primitive metanephric tubular cells. A previous study identified
      BRAF V600E mutations in approximately 90% of MA and found that similar BRAF exon
      15 mutations are exceedingly rare in other common renal tumors, including renal
      cell carcinoma and oncocytoma. A recent follow-up study has validated mutation
      specific immunohistochemistry (IHC) for detection of BRAF V600E mutations in a
      small cohort of MA. Here, we extend these findings to a larger, independent
      cohort of MA, demonstrating an overall 88% sensitivity and 100% specificity for
      BRAF V600E IHC. In addition, we report 2 cases of MA with novel BRAF exon 15
      mutations, including a V600D missense mutation and a compound V600D and K601L
      missense mutation. Finally, we evaluate BRAF V600E IHC in a large tissue
      microarray cohort of common renal tumors and find no significant expression in
      several renal cell carcinoma subtypes. These data support a role for BRAF V600E
      IHC in diagnostically challenging cases of MA and expand the spectrum of BRAF
      exon 15 mutations in this uncommon but unique renal neoplasm. 

PMID- 25602794
TI  - Epithelioid malignant peripheral nerve sheath tumor: clinicopathologic analysis
      of 63 cases.
AB  - Epithelioid malignant peripheral nerve sheath tumor (EMPNST) is rare and differs
      from conventional malignant peripheral nerve sheath tumor by showing diffuse S
      100 protein positivity, infrequent association with NF1, and occasional origin in
      a schwannoma. Loss of INI1 expression is seen in a subset of tumors. The purpose
      of this study was to further define clinicopathologic features and outcome data
      in a large series of EMPNST. Sixty-three cases were identified in consultation
      files. The patient group consisted of 33 men and 30 women; the median age was 44
      years (range, 6 to 80 y). One patient was reported to have NF1. One patient had 3
      seemingly separate primary EMPNSTs during his 12-year clinical course. The median
      tumor size was 3.0 cm (range, 0.4 to 20 cm), and tumors were located most
      frequently on the lower extremity (30/63; 48%) and trunk (16/63; 25%). Most
      tumors were superficial (5 dermal, 38 subcutaneous); 15 were subfascial, and 5
      were visceral. Microscopically, tumors comprised a relatively uniform but clearly
      atypical population of epithelioid cells. The majority of tumors demonstrated a
      multilobular growth pattern, with lobules and nests surrounded by myxoid and/or
      fibrous stroma. Tumor cells were round, polygonal, or ovoid and had round
      vesicular nuclei and abundant amphophilic to palely eosinophilic cytoplasm. Focal
      spindled morphology was seen in one third of cases. Most tumors (55/63; 87%)
      showed marked cytologic atypia with irregular vesicular nuclei and prominent
      nucleoli. Mitotic rate ranged from 1 to 46/10 HPF (median, 5/10 HPF); atypical
      mitotic figures were seen in 7 cases. Necrosis was present in 17 tumors. Twelve
      tumors were associated with a nerve. Nine tumors arose in a schwannoma (6
      conventional type, 3 epithelioid) and 1 in a neurofibroma (in the NF1 patient).
      All tumors expressed S-100 protein, and the majority showed strong and diffuse
      staining (87%; 55/63). There was no expression of the melanocytic markers Mart
      1/Melan-A (0/58), HMB-45 (0/57), and MiTF (0/9). Other immunohistochemical
      results included variable staining for GFAP (24/40; 60%) and EMA (4/29; 14%),
      whereas keratin was consistently negative (0/33). INI1 expression was lost in 67%
      of tumors examined (35/52). Most tumors were treated by surgical resection; 13
      also received chemotherapy and/or radiation. Follow-up data were available for 31
      cases and ranged in duration from 3 months to 20 years (median, 36 mo). Twenty
      two patients have no evidence of disease at the time of follow-up. Nine patients
      developed local recurrence, 3 of whom were reported to be disease-free at the
      time of latest follow-up (44 mo, 19 y, and 20 y). Five patients developed distant
      metastases, and 4 patients died of disease (including 2 with unresectable
      recurrent tumors). Recurrence, metastasis, and disease-related death were
      observed independent of anatomic site or depth. In summary, EMPNST is a
      morphologically distinct variant that most commonly affects adults on the lower
      extremity or trunk, although a wide age range and site distribution are seen.
      Most tumors arise in superficial soft tissue, are diffusely S-100 positive, and
      two thirds show INI1 loss. On the basis of available follow-up information there
      is a comparatively low risk for recurrence and metastasis, irrespective of tumor
      depth. 

PMID- 25602795
TI  - Pediatric non-Helicobacter pylori atrophic gastritis: a case series.
AB  - Although autoimmune atrophic gastritis is classically a disease of elderly
      adults, recent studies have described the disease in younger adults, particularly
      in those with other autoimmune diseases and iron-deficiency anemia. Atrophic
      gastritis in pediatrics is a rare and possibly underdiagnosed entity that has
      been primarily reported as single-case reports. This retrospective study of
      atrophic gastritis not associated with Helicobacter pylori infection was
      performed to further expand the knowledge of clinical presentation, pathologic
      findings, and natural history of this disease in the pediatric population. Twelve
      patients with a histologic diagnosis of atrophic gastritis were identified, with
      an age range of 8 months to 18 years. Seven had other autoimmune diseases and/or
      immunodeficiency. Atrophy was confined to the oxyntic mucosa in 10 patients, with
      intramucosal inflammation in a diffuse or basal-predominant pattern. Active
      inflammation was present in 7 patients. Pseudopyloric, intestinal, or
      squamous/mucinous metaplasia was seen at initial biopsy or on follow-up in 8
      patients, and enterochromaffin-like cell hyperplasia was seen in 5. One patient
      developed an adenocarcinoma during the follow-up period of 10 years. Two false
      negative diagnoses were retrospectively identified. In the majority of cases, the
      possibility of atrophic gastritis was not raised by the submitting physician, and
      the endoscopic findings were not specific. Therefore, accurate diagnosis requires
      a high degree of suspicion on the part of the pathologist, and the diagnosis
      should be considered particularly in patients with a clinical history of other
      autoimmune diseases or iron-deficiency anemia. 

PMID- 25602796
TI  - The Interpretive Variability of Cervical Biopsies and Its Relationship to HPV
      Status.
AB  - Diagnostic interpretation of a cervical biopsy is a key element in the decision
      to treat or not to treat a woman with an abnormal screening test. This study
      assesses the variability of these diagnostic interpretations on a population
      basis using the New Mexico HPV Pap Registry database. An experienced panel of
      gynecologic pathologists reviewed a stratified random sample of 6272 biopsies,
      which was then extrapolated to the entire population of 21,297 biopsies read by
      the community pathologists. Diagnoses by the community and panel pathologists
      were compared, and paired diagnoses were correlated with positivity for human
      papillomavirus 16 (HPV16) and any high-risk HPV as objective measures of
      progressive potential. Panel agreement with the community diagnosis was 38.2% for
      cervical intraepithelial neoplasia grade 1 (CIN1), 38.0% for CIN grade 2 (CIN2),
      68.0% for CIN grade 3 (CIN3), and 70.6% for cancer. The kappa value was 0.46
      overall but higher for dichotomous categorization based on CIN2 or CIN3 cutoff
      points (0.68 and 0.67, respectively). On a population basis, there were fewer
      CIN1 and more negative diagnoses in the panel review but similar proportions of
      CIN2 and CIN3. HPV16 and high-risk HPV positivity increased with disease
      severity, but panel review did not improve the correlation of higher-grade
      disease with these objective measures. In this population-based study of the
      variability in cervical diagnoses, we noted significant variability in the
      community and panel diagnoses, especially for CIN2, the threshold for excisional
      treatment. New biomarkers are needed to more accurately stratify precursor
      lesions according to their malignant potential. 

PMID- 25602798
TI  - Primary hepatic tumors with myxoid change: morphologically unique hepatic
      adenomas and hepatocellular carcinomas.
AB  - Mucin production in primary liver neoplasms is typically interpreted as evidence
      for biliary differentiation. However, we have observed benign and malignant liver
      tumors that have abundant extracellular myxoid/mucinous material, yet have only
      evidence of hepatocellular differentiation. To further characterize these unusual
      findings, 9 cases were identified and further studied. Four cases were hepatic
      adenomas, whereas 5 were hepatocellular carcinomas. Extracellular myxoid/mucinous
      material was diffuse in 7 cases and patchy in 2 cases. The extracellular
      myxoid/mucinous material was typically weakly mucicarmine positive (N=6) and
      Alcian blue positive (N=8). All tumors were well differentiated, and none had
      evidence for biliary differentiation by morphology or immunohistochemistry. The
      hepatic adenomas arose in nondiabetic and nonobese patients. Both the hepatic
      adenomas and the hepatocellular carcinomas were strongly and diffusely HepPar1
      positive, CK19 negative, and showed loss of LFABP protein expression. These
      findings indicate that extracellular myxoid/mucinous material in isolation should
      not be interpreted as cholangiocarcinoma. Furthermore, the unique morphology, the
      clinical characteristics, and the immunophenotype results suggest that myxoid
      hepatic adenomas and hepatocellular carcinoma may be unique tumor variants. 

PMID- 25602797
TI  - Clinicopathologic and prognostic significance of multiple hormone expression in
      pancreatic neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors (PanNETs) produce variable peptide hormones. The
      expression status of some hormones has been linked to the biological and clinical
      behaviors of PanNETs. A total of 226 surgically resected PanNETs were selected.
      Immunolabeling for peptide hormones was compared with various clinicopathologic
      factors, including patient survival. Expression of insulin, glucagon-like peptide
      1, glucagon, gastrin, somatostatin, and serotonin were observed in 56 (24.8%), 41
      (18.1%), 25 (11.1%), 5 (2.2%), 5 (2.2%), and 4 (1.8%) cases, respectively.
      Expression of 1, 2, and 3 hormones was noted in 70 (31.0%), 28 (12.4%), and 3
      (1.3%) cases, respectively; 125 cases (55.3%) were negative for all hormones.
      PanNETs with insulin and glucagon-like peptide 1 expression were associated with
      a lower grade, smaller size, lower pT and pN classifications, absence of
      lymphovascular invasion, and lymph node metastasis and had better survival by
      univariate analysis, whereas PanNETs with gastrin expression were associated with
      a higher grade, larger size, higher pT and pN classifications, presence of
      lymphovascular invasion, and lymph node metastasis and had worse survival.
      Gastrin expression, increased age, and tumor grade were negative prognostic
      factors in multivariate analysis. As the number of hormones expressed increased,
      the survival rate of PanNET patients increased. In summary, PanNET patients
      showing insulin or glucagon-like peptide 1 expression and increased numbers of
      expressed hormones had a better survival outcome by univariate analysis, whereas
      gastrin expression was a negative prognostic indicator in surgically resected
      PanNET patients. 

PMID- 25602799
TI  - Characteristics of the gastric mucosa in patients with intestinal metaplasia.
AB  - Gastric intestinal metaplasia (IM) occurs in response to different injuries, some
      of which involve increased risk for gastric cancer, whereas others may not. The
      background in which IM arises has not been systematically investigated. This
      study was designed to determine the relative prevalence of the histopathologic
      conditions of the gastric mucosa associated with IM in a large cohort. We
      extracted from a database patients who had undergone esophagogastroduodenoscopy
      with gastric biopsies between January 2008 and December 2013 in endoscopy centers
      throughout the United States. For each subject we recorded demographic, clinical,
      and histopathologic information. We stratified patients according to the presence
      of IM and compared the prevalence of Helicobacter pylori infection, reactive
      gastropathy, minimal inflammatory and gastropathy changes, mucosal atrophy,
      gastric polyps, cancer, and lymphoma in the 2 groups. IM, present in 8.4% of the
      810,821 unique patients, increased with age and was more common in male than in
      female individuals. Compared with other Americans, East Asian ancestry was
      associated with a 5-fold risk for IM. Helicobacter gastritis and its sequelae
      were present in 42.2% of patients with IM, and reactive gastropathy in 17.3%. In
      >50% of patients under the age of 30 and in 26% of older adults, foci of IM
      occurred in an almost normal gastric mucosa. Thus, approximately half of the
      patients with IM had no histopathologic evidence of current or previous
      Helicobacter gastritis, whereas almost one fifth had a background of reactive
      gastropathy. Longitudinal studies are needed to determine the relative risk for
      gastric cancer in patients with IM associated and not with Helicobacter
      infection. 

PMID- 25602800
TI  - Peculiar histiocytic lesions with massive lanthanum deposition in dialysis
      patients treated with lanthanum carbonate.
AB  - Pathologic lesions caused by lanthanum carbonate (LC), a recently developed
      phosphate-binding agent, have not been recorded. A peculiar gastroduodenal
      histiocytic lesion associated with a mucosal lanthanum overload was reported. Our
      routine gastrointestinal biopsy series included 6 cases with heavy lanthanum
      burden in the gastroduodenal mucosa. In addition to routine histopathologic
      examinations, a series of immunohistochemical analysis and electron microscopic
      examinations associated with x-ray diffraction and elemental analysis were
      performed. Six cases, 3 of male and 3 of female individuals with ages from 59 to
      69 years, were all patients of end-stage renal diseases managed under dialysis
      and treated with LC for >21 months. Endoscopic examinations demonstrated gastric
      erosions in 3, gastric polyps in 2, and duodenal ulcer in 1. In the mucosal
      layer, there were numerous non-Langerhans cell histiocytes, stained with CD68 but
      not S100 protein, engulfing a large amount of mineral-like materials. An electron
      microscopic and elemental analysis revealed a similar distribution of lanthanum
      and phosphorus in the histiocytes. Long-standing LC administration can cause
      massive mucosal accumulation of lanthanum in the tissue histiocytes associated
      with several forms of gastroduodenal lesions. A long-standing outcome is not
      clear at present; hence, careful follow-up studies of these patients may be
      needed. 

PMID- 25602801
TI  - Clinical, histopathologic, and genomic features of Spitz tumors with ALK fusions.
AB  - Activating kinase fusions have recently been described as early oncogenic events
      that are mutually exclusive with HRAS and BRAF mutations in Spitz tumors. Here,
      we report a series of 32 Spitz tumors with ALK fusions (6 Spitz nevi, 22 atypical
      Spitz tumors, and 4 spitzoid melanomas) in patients ranging from 5 months to 64
      years (median=12 y) of age. The tumors typically presented as exophytic papules
      on the extremities and were occasionally darkly pigmented. In addition to ALK
      fusions previously described in other tumor types (NPM1-ALK, TPR-ALK), we
      identified 2 novel ALK fusions (CLIP1-ALK and GTF3C2-ALK) in our cohort of Spitz
      tumors. Array comparative genomic hybridization of 19 of these tumors
      demonstrated a high frequency of chromosome 2 aberrations (where ALK resides,
      63%) and chromosome 1p loss in 37% of the cases. Spitz tumors with ALK fusions
      demonstrated unique histopathologic features. Clefts and small vesicle-like
      spaces were arrayed between plump spindled melanocytes with fibrillar cytoplasm
      and enlarged nuclei. These melanocytes were typically arrayed in elongated and
      fusiform nests with radial orientation. The tumors often had extension into the
      dermis or subcutis with a wedge-shaped or bulbous lower border (45% and 17%,
      respectively). An infiltrative growth pattern was often present at the periphery
      of the tumor and was highlighted by ALK immunohistochemistry. In conclusion,
      Spitz tumors with ALK rearrangement show distinct histopathologic features that
      should aid in improving classification of these diagnostically challenging
      tumors. 

PMID- 25602803
TI  - Evaluation of the patient with an exposure-related disease: the occupational and
      environmental history.
AB  - PURPOSE OF REVIEW: Although the process of taking an occupational and
      environmental history has remained largely the same, the context in which it is
      done has changed dramatically over recent years. This review examines the role of
      the occupational and environmental history in the context of the changing nature
      of medical practice and discusses methods for evaluating patients with
      contemporary exposure-related respiratory illnesses. RECENT FINDINGS:
      Surveillance for occupational lung disease using mnemonic devices, screening
      questions and the use of structured questionnaires can significantly increase the
      likelihood and accuracy of detection. Electronic health records likewise can be
      adapted to include the most important elements of the occupational and
      environmental history. SUMMARY: The emergence of new technologies and industries
      will lead to respiratory diseases in novel occupational and environmental
      contexts. Using the methods described herein can make detecting these diseases
      easier and less time-consuming.

PMID- 25602802
TI  - Semiconductor-based sequencing of genome-wide DNA methylation states.
AB  - Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is a widely used
      approach to study DNA methylation genome-wide. Here, we developed a MeDIP-Seq
      protocol compatible with the Ion Torrent semiconductor-based sequencing platform
      that is low cost, rapid, and scalable. We applied this protocol to demonstrate
      MeDIP-Seq on the Ion Torrent platform provides adequate coverage of CpG
      cytosines, the methylation states of which we validated at single-base resolution
      on the Infinium HumanMethylation450 BeadChip array, and accurately identifies
      sites of differential DNA methylation. Furthermore, we applied an integrative
      approach to further investigate and confirm the role of DNA methylation in
      alternative splicing and to profile 5mC and 5hmC variants of DNA methylation in
      normal human brain tissue that is localized over distinct genomic regions. These
      applications of MeDIP-Seq on the Ion Torrent platform have broad utility and add
      to the current methodologies for profiling genome-wide DNA methylation states in
      normal and disease conditions. 

PMID- 25602804
TI  - Beryllium and other metal-induced lung disease.
AB  - PURPOSE OF REVIEW: Metals can cause disease of the upper and lower respiratory
      tract that mirror disease due to other causes, such as asthma, rhinosinusitis,
      acute bronchitis, chronic bronchitis, acute pneumonitis, bronchogenic carcinoma,
      and interstitial lung disease. This article will describe some uncommon and
      unique lung diseases that can be induced by metals. RECENT FINDINGS: Our
      understanding of old occupational lung diseases, such as chronic beryllium
      disease, continues to increase. New exposures in the workplace, such as indium,
      have been identified as novel occupational hazards. New forms of exposure, such
      as titanium dioxide nanoparticles, create risk of lung disease that is not seen
      with larger particles. SUMMARY: Knowledge of several unusual and/or unique
      occupational lung diseases should prompt questioning about a patient's
      occupational history, which may uncover an occupational, rather than an
      idiopathic, lung disease.

PMID- 25602805
TI  - Acute effect of cycling intervention on carotid arterial hemodynamics: basketball
      athletes versus sedentary controls.
AB  - OBJECTIVE: To compare the acute effects of a cycling intervention on carotid
      arterial hemodynamics between basketball athletes and sedentary controls.
      METHODS: Ten young long-term trained male basketball athletes (BA) and nine age
      matched male sedentary controls (SC) successively underwent four bouts of
      exercise on a bicycle ergometer at the same workload. Hemodynamic variables at
      right common carotid artery were determined at rest and immediately following
      each bout of exercise. An ANCOVA was used to compare differences between the BA
      and SC groups at rest and immediately following the cycling intervention. The
      repeated ANOVA was used to assess differences between baseline and each bout of
      exercise within the BA or SC group. RESULTS: In both groups, carotid hemodynamic
      variables showed significant differences at rest and immediately after the
      cycling intervention. At rest, carotid arterial stiffness was significantly
      decreased and carotid arterial diameter was significantly increased in the BA
      group as compared to the SC group. Immediately following the cycling
      intervention, carotid arterial stiffness showed no obvious changes in the BA
      group but significantly increased in the SC group. It is worth noting that while
      arterial stiffness was lower in the BA group than in the SC group, the
      oscillatory shear index (OSI) was significantly higher in the BA group than in
      the SC group both at rest and immediately following the cycling intervention.
      CONCLUSION: Long-term basketball exercise had a significant impact on common
      carotid arterial hemodynamic variables not only at rest but also after a cycling
      intervention. The role of OSI in the remodeling of arterial structure and
      function in the BA group at rest and after cycling requires clarification.

PMID- 25602807
TI  - Net global warming potential and greenhouse gas intensity influenced by
      irrigation, tillage, crop rotation, and nitrogen fertilization.
AB  - Little information exists about how global warming potential (GWP) is affected by
      management practices in agroecosystems. We evaluated the effects of irrigation,
      tillage, crop rotation, and N fertilization on net GWP and greenhouse gas
      intensity (GHGI or GWP per unit crop yield) calculated by soil respiration (GWP
      and GHGI) and organic C (SOC) (GWP and GHGI) methods after accounting for CO
      emissions from all sources (irrigation, farm operations, N fertilization, and
      greenhouse gas [GHG] fluxes) and sinks (crop residue and SOC) in a Lihen sandy
      loam from 2008 to 2011 in western North Dakota. Treatments were two irrigation
      practices (irrigated vs. nonirrigated) and five cropping systems (conventional
      till malt barley [ L.] with N fertilizer [CTBN], conventional-till malt barley
      with no N fertilizer [CTBO], no-till malt barley-pea [ L.] with N fertilizer [NTB
      P], no-till malt barley with N fertilizer, and no-till malt barley with no N
      fertilizer [NTBO]). While CO equivalents were greater with irrigation, tillage,
      and N fertilization than without, NO and CH fluxes were 2 to 218 kg CO eq. ha
      greater in nonirrigated NTBN and irrigated CTBN than in other treatments.
      Previous year's crop residue and C sequestration rate were 202 to 9316 kg CO eq.
      ha greater in irrigated NTB-P than in other treatments. Compared with other
      treatments, GWP and GWP were 160 to 9052 kg CO eq. ha lower in irrigated and
      nonirrigated NTB-P. Similarly, GHGI and GHGI were lower in nonirrigated NTB-P
      than in other treatments. Regardless of irrigation practices, NTB-P may lower net
      GHG emissions more than other treatments in the northern Great Plains. 

PMID- 25602808
TI  - Injection of Dicyandiamide-Treated Pig Slurry Reduced Ammonia Volatilization
      without Enhancing Soil Nitrous Oxide Emissions from No-Till Corn in Southern
      Brazil.
AB  - There is a lack of information on how placement in soil and nitrification
      inhibitors affects nitrous oxide (NO) and ammonia (NH) emissions from pig slurry
      (PS) applied under no-till (NT) conditions. Our objective was to determine the
      impact of injecting PS and treating it with the nitrification inhibitor
      dicyandiamide (DCD) on NH and NO emissions from soils under NT in subtropical
      southern Brazil. The emissions of these gases were compared for shallow (~ 10 cm)
      injection and surface broadcasting of PS with and without DCD (8.1-10.0 kg ha;
      6.5-8.4% of applied NH-N). Measurements were made at two sites during two summer
      growing seasons under NT corn crops. Injection reduced NH volatilization by 70%
      but increased NO emissions 2.4-fold (from 2628 to 6198 g NO N ha) compared with
      surface broadcast application. Adding DCD to PS inhibited nitrification and
      reduced NO emissions by an average of 28% (730 g NO-N ha) for surface broadcast
      and 66% (4105 g NO-N ha) for injection but did not increase NH volatilization.
      Consequently, NO emission factors were much higher for injection (3.6%) than for
      surface broadcast (1.3%) application and were reduced (0.9%) when DCD was added
      to injected PS. In conclusion, the injection of DCD-treated slurry is a
      recommendable practice for reducing NH and NO emissions when applying PS on NT
      corn in southern Brazil. 

PMID- 25602806
TI  - Autophagy and ubiquitination in cardiovascular diseases.
AB  - A main function of the heart is to pump blood to the tissues and organs of the
      body. Although formed by different types of cells, the cardiomyocytes are the
      ones responsible for the coordinated and synchronized heart contraction. Given
      their low mitotic activity, cardiomyocytes largely depend on protein degradation
      mechanisms to maintain proteostasis and energetic balance. Autophagy, one of the
      main pathways whereby cells eliminate damaged, nonfunctional, or obsolete
      proteins, and organelles, is vital to ensure cell function, including in
      cardiomyocytes, both in rest and stress conditions. However, the impact of
      autophagy activation in the heart, being either protective or harmful, is not
      consensual and likely depends upon the severity of the stimuli and consequently
      the autophagy players involved. One of the signals that direct proteins for
      autophagy degradation, namely in the context of heart disorders, is ubiquitin.
      Indeed, the attachment of ubiquitin moieties to a target substrate and further
      recognition by autophagy adaptors constitute a main regulatory pathway that
      directs proteins to the lysosome. Therefore, a better understanding of the
      mechanisms and signals that regulate the autophagy process in the heart,
      including substrates targeting, is of utmost importance to design new approaches
      directed to this degradation pathway. We have previously shown that
      ubiquitination of the gap junction (GJ) protein Connexin43 (Cx43) triggers its
      degradation by autophagy through a process that requires the ubiquitin adaptors
      epidermal growth factor receptor substrate 15 (Eps15) and p62. This is
      particularly relevant in the heart because GJs, that form intercellular channels,
      are responsible for the rapid and efficient anisotropic propagation of the
      electrical impulse through the cardiomyocytes, essential for synchronized
      contraction of the cardiac muscle. In this review, we present recent studies
      devoted to the involvement of autophagy in heart homeostasis, with a particular
      focus on ubiquitin and GJs. 

PMID- 25602809
TI  - Atmospheric dust accumulation on native and non-native species: effects on gas
      exchange parameters.
AB  - Plants are continuously exposed to atmospheric particulate matter (dust), and
      their leaves are the main receptors of deposited dust. The objective of this
      study was to assess the effects of dust deposition on leaf gas exchange
      parameters of 17 native and non-native tree and shrub species growing in Gran San
      Miguel de Tucuman in northwestern Argentina. Maximum assimilation rate (),
      stomatal conductance (), transpiration rate (), internal CO concentration (), and
      instantaneous water-use efficiency (WUE) were measured in cleaned leaves (CL) and
      dusted leaves (DL) of different species on November 2010, July 2011, and
      September 2011. In almost all studied species, gas exchange parameters were
      significantly affected by dust deposition. Values for , , and of DL were
      significantly reduced in 11, 12, and 14 species compared with CL. Morphological
      leaf traits seem to be related to reduction. Indeed, L. and (Mart. ex DC.)
      Standl. species with pubescent leaves and thick ribs showed the highest reduction
      percentages. Contrarily, and WUE were increased in DL but were less responsive to
      dust deposition than other parameters. Increases of and WUE were significant in 5
      and 11 species, respectively. Correlation analyses between /, /, and / pairs
      showed significant positive linear correlations in CL and DL of many studied
      species, including small and tall plants. These results suggest that leaf
      stomatal factors and shade-induced effect by accumulated dust are primarily
      responsible for the observed reductions in photosynthesis rate of DL. 

PMID- 25602810
TI  - Speciation and isotopic composition of sulfur in limestone soil and yellow soil
      in karst areas of southwest china: implications of different responses to Acid
      deposition.
AB  - The contents and stable S isotope ratio (deltaS) values of total S, organic S, SO
      S, and total reduced inorganic S (TRS) in typical limestone soil and yellow soil
      were analyzed in this study to examine the general distributions of S forms and
      their deltaS values in soils in karst areas of southwest China. Under a similar
      level of acid deposition, the vertical profiles of the S forms and their deltaS
      values differed in limesto?ne soil and yellow soil, indicating the different
      geochemical responses of these soils to acid deposition. The deposited SO was
      retained as organic S in both soils. The depletion in S of TRS relative to SO and
      the parallel increasing deltaS values of TRS and SO indicate a bacterial
      reduction process of sulfate in both soils. The different extents of C-bonded S
      mineralization and organic sulfate transport explain the different vertical
      profiles of total S and organic S contents in both soils. Sulfate adsorption in
      limestone soil was negligible because of high pH values. Sulfate adsorption in
      yellow soil was another important S retention process in addition to biological S
      retention to form organic S and TRS because of low pH values. The effect of acid
      deposition on yellow soil appeared more serious because of the accumulation and
      leaching of deposited SO, which can result in soil acidification and accelerate
      the loss of basic cations from yellow soil. However, compared with yellow soil,
      limestone soil released more S into rivers by organic S mineralization after a
      large decrease in annual S deposition rate. 

PMID- 25602811
TI  - Cattle methane emission and pasture carbon dioxide balance of a grazed grassland.
AB  - Grasslands constitute a major land use globally and are a potential sink of
      atmospheric carbon dioxide (CO). They are also an important habitat for wildlife
      and a source of feed that supports ruminant livestock production. However, the
      presence of ruminants grazing these grasslands is also a source of methane (CH)
      that contributes to buildup of greenhouse gases in the atmosphere. Our study
      measured enteric CH from 40 confined heifers in 1-ha paddocks using a dispersion
      model and CO exchange from an adjacent grassland site using a micrometeorological
      technique. The study was conducted at a mixed prairie grassland located in
      southern Alberta, Canada. The mean (standard error) CH emission was 189 (+/- 6) g
      animal d over four campaigns (over a 3-yr period). The daily averaged CO exchange
      from the grassland peaked at +2.2 g m h (sink) in early July and declined to
      negative values (source) in mid-August. Annually, the grazed grassland was either
      a net sink for carbon (C) at +40 kg C ha or a small source at -7 kg C ha
      depending on a cattle stocking density of 0.1 or 0.2 animals ha, respectively.
      However, in basing the exchange on CO equivalence (CO), both stocking densities
      resulted in the grazed grassland being a source of greenhouse gas of -9 or -338
      kg CO ha y. This study illustrates the need to consider the cattle CH emissions
      and the stocking density when evaluating the environmental sustainability of
      grazed grasslands. 

PMID- 25602812
TI  - Soil nitrous oxide emissions after deposition of dairy cow excreta in eastern
      Canada.
AB  - Urine and dung deposited by grazing dairy cows are a major source of nitrous
      oxide (NO), a potent greenhouse gas that contributes to stratospheric ozone
      depletion. In this study, we quantified the emissions of NO after deposition of
      dairy cow excreta onto two grassland sites with contrasting soil types in eastern
      Canada. Our objectives were to determine the impact of excreta type, urine-N
      rate, time of the year, and soil type on annual NO emissions. Emissions were
      monitored on sandy loam and clay soils after spring, summer, and fall urine (5
      and 10 g N patch) and dung (1.75 kg fresh weight dung) applications to perennial
      grasses in two successive years. The mean NO emission factor (EF) for urine was
      1.09% of applied N in the clay soil and 0.31% in the sandy loam soil, estimates
      much smaller than the default Intergovernmental Panel on Climate Change (IPCC)
      default value for total excreta N (2%). Despite variations in urine composition
      and in climatic conditions, these soil-specific EFs were similar for the two
      urine-N application rates. The time of the year when urine was applied had no
      impact on emissions from the sandy loam soil, but greater EFs were observed after
      summer (1.59%) than spring (1.14%) and fall (0.55%) applications in the clay
      soil. Dung deposition impact on NO emission was smaller than that of urine, with
      a mean EF of 0.15% in the sandy loam soil and 0.08% in the clay soil. Our results
      suggest (i) that the IPCC default EF overestimates NO emissions from grazing
      cattle excreta in eastern Canada by a factor of 4.3 and (ii) that a region
      specific inventory methodology should account for soil type and should use
      specific EFs for urine and dung. 

PMID- 25602813
TI  - Treatment of dissolved perchlorate, nitrate, and sulfate using zero-valent iron
      and organic carbon.
AB  - Waters containing ClO and dissolved NO, derived from detonated explosives and
      solid propellants, often also contain elevated concentrations of other dissolved
      constituents, including SO. Four column experiments, containing mixtures of
      silica sand, zero-valent Fe (ZVI) and organic C (OC) were conducted to evaluate
      the potential for simultaneous removal of NO, SO and ClO. Initially, the flow
      rate was maintained at 0.5 pore volumes (PV) d and then decreased to 0.1 PV d
      after 100 PV of flow. Nitrate concentrations decreased from 10.8 mg L (NO-N) to
      trace levels through NO reduction to NH using ZVI alone and through
      denitrification using OC. Observations from the mixture of ZVI and OC suggest a
      combination of NO reduction and denitrification. Up to 71% of input SO (24.5 +/-
      3.5 mg L) was removed in the column containing OC, and >99.7% of the input ClO
      (857 +/- 63 MUg L) was removed by the OC- and (ZVI + OC)-containing columns as
      the flow rate was maintained at 0.1 PV d. Nitrate and ClO removal followed first
      order and zero-order rates, respectively. Nitrate >2 mg L (NO-N) inhibited ClO
      removal in the OC-containing column but not in the (ZVI + OC)-containing column.
      Sulfate did not inhibit ClO degradation within any of the columns. 

PMID- 25602814
TI  - Effects of warming and nutrient enrichment on how grazing pressure affects leaf
      litter-colonizing bacteria.
AB  - In view of current scenarios of global environmental change, we investigated the
      effects of warming and nutrient addition (N and P) on the impact of detritivores
      on density and community composition of leaf litter-colonizing bacteria in a
      freshwater environment. Within 10 d, detritivorous amphipods () reduced bacterial
      numbers at 10 degrees C and to a lesser degree at 15 degrees C. However, the
      detritivore-induced decrease in bacterial numbers was compensated for by nutrient
      addition. After 31 d of incubation, amphipods reduced bacterial numbers only at
      15 degrees C, and nutrient addition did not counteract detritivore effects.
      Similarly, changes in bacterial numbers in response to nutrient addition were
      more pronounced at low temperature within 10 d, whereas nutrient effects were
      stronger at high temperature after 31 d of incubation. Thus, warming without
      detritivores did not affect bacterial numbers under low-nutrient conditions (10
      d). When detritivores were present, warming increased bacterial density
      significantly just under high-nutrient conditions ( < 0.05). After 31 d of
      incubation, warming did not affect bacterial density in detritivore-free controls
      in both nutrient conditions and did not affect bacterial density in both nutrient
      conditions in the presence of detritivores. Warming exhibited a significant
      effect on the composition of litter-associated bacterial communities irrespective
      of nutrient load ( < 0.05), whereas nutrients had less consistent effects. We
      conclude that warming, and to a lesser degree nutrient enrichment, may have
      influence on grazer-induced changes in bacterial biofilm composition, whereas
      nutrient enrichment may mostly interfere with those processes that depend on
      bacterial density. 

PMID- 25602815
TI  - Model-based Scenario Analysis of the Impact of Remediation Measures on Metal
      Leaching from Soils Contaminated by Historic Smelter Emissions.
AB  - A spatially distributed model for leaching of Cd from the unsaturated zone was
      developed for the Belgian-Dutch transnational Kempen region. The model uses as
      input land-use maps, atmospheric deposition data, and soil data and is part of a
      larger regional model that simulates transport of Cd in soil, groundwater, and
      surface water. A new method for deriving deposition from multiple sites was
      validated using soil data in different wind directions. Leaching was calculated
      for the period 1890 to 2010 using a reconstruction of metal loads in the region.
      The model was able to reproduce spatial patterns of concentrations in soil and
      groundwater and predicted the concentration in shallow groundwater adequately
      well for the purpose of evaluating management options. For 42% of the data
      points, measurements and calculations were within the same concentration class.
      The model was used for forecasting under a reference scenario, an autonomous
      development scenario including climate change, and a scenario with implementation
      of remediation measures. The impact of autonomous development (under the most
      extreme scenario of climatic change) amounted to an increase of 10% in cumulative
      Cd flux after 100 yr as compared with the reference scenario. The impact of
      remediation measures was mainly local and is less pronounced (i.e., only 3%
      change in cumulative flux at the regional scale). The integrated model served as
      a tool to assist in developing management strategies and prioritization of
      remediation of the wide-spread heavy metal contamination in the region. 

PMID- 25602816
TI  - Transferability of SWAT Models between SWAT2009 and SWAT2012.
AB  - In recent years, the Soil and Water Assessment Tool (SWAT) has experienced
      upgrades with enhanced functionalities and modeling capacities as it gets to the
      current version, SWAT2012. Changes in the SWAT code on a specific process may
      result in propagating influences in the output of other related processes. In
      this study, the characteristic significance of the enhancements in SWAT code was
      investigated using the two recent versions, SWAT2009 and SWAT2012. Using a global
      optimization technique, each model was calibrated for flow, sediment, and
      nutrient and then tested for transferability of parameters between the models.
      Results indicate that flow and water quality output were well calibrated with
      both models. However, the calibrated parameters determined by SWAT2009 and
      SWAT2012 were noticeably different, due mostly to the enhancements made in
      SWAT2012. Our results indicate that only the stream flow result was reliable when
      the models were upgraded or downgraded between the two versions after
      calibration. Sediment prediction was marginally reliable. SWAT parameters were
      nontransferrable if nutrient was the main output. The differences are due to
      various reasons, such as disparities in algorithms at the process level and
      propagation of the resulting uncertainty into higher-order processes. 

PMID- 25602817
TI  - Nitrate leaching in californian rice fields: a field- and regional-scale
      assessment.
AB  - Irrigated croplands can be a major source of nitrate-N (NO-N) in groundwater due
      to leaching. In California, where high NO-N levels have been found in some areas
      of the Central Valley aquifer, the contribution from rice systems has not been
      determined. Nitrate leaching from rice systems was evaluated from soil cores (0-2
      m), from the fate of N fertilizer in replicated microplots, and from about 145
      regional groundwater wells. Soil NO-N concentrations were <=3.3 mg kg (usually <1
      mg kg) below the root zone (below 33 cm depth). In pore-water samples, NO-N was
      observed only below the root zone during the first 2 wk after the onset of
      flooding in either the growing season or the winter fallow period and was always
      <=8.4 mg L. Fertilizer N accounted for 0 to 11.8% of NO-N in pore-water samples
      below the root zone. One year after application, based on an analysis of soil
      core samples, on average 2.5% of fertilizer N was recovered as N below the root
      zone (33-100 cm), possibly due to leaching in permeable soils or via preferential
      flow through cracks in heavy clay soils. Based on a regional assessment,
      groundwater samples from wells that are located in proximity to rice fields all
      had measured median NO-N and NO-N levels below 1 mg L. These results indicate
      that NO-N leaching from the majority of California rice systems poses little risk
      to groundwater under current crop management practices. 

PMID- 25602818
TI  - Agriculture's Contribution to Nitrate Contamination of Californian Groundwater
      (1945-2005).
AB  - Nitrogen (N) use in intensive agriculture can degrade groundwater resources.
      However, considerable time lags between groundwater recharge and extraction
      complicate source attribution and remedial responses. We construct a historic N
      mass balance of two agricultural regions of California to understand trends and
      drivers of past and present N loading to groundwater (1945-2005). Changes in
      groundwater N loading result from historic changes in three factors: the extent
      of agriculture (cropland area and livestock herd increased 120 and 800%,
      respectively), the intensity of agriculture (synthetic and manure waste effluent
      N input rates increased by 525 and 1500%, respectively), and the efficiency of
      agriculture (crop and milk production per unit of N input increased by 25 and
      19%, respectively). The net consequence has been a greater-than-order-of
      magnitude increase in nitrate (NO) loading over the time period, with 163 Gg N yr
      now being leached to groundwater from approximately 1.3 million ha of farmland
      (not including alfalfa [ L.]). Meeting safe drinking water standards would
      require NO leaching reductions of over 70% from current levels through reductions
      in excess manure applications, which accounts for nearly half of all groundwater
      N loading, and through synthetic N management improvements. This represents a
      broad challenge given current economic and technical conditions of California
      farming if farm productivity is to be maintained. The findings illustrate the
      growing tension-characteristic of agricultural regions globally-between
      intensifying food, feed, fiber, and biofuel production and preserving clean
      water. 

PMID- 25602820
TI  - Cadmium concentrations in new zealand pastures: relationships to soil and climate
      variables.
AB  - Cadmium (Cd) is a nonessential element that occurs at above-background
      concentrations in many New Zealand (NZ) soils. Most of this Cd is due to the
      historical application of single superphosphate that was made from Nauru
      phosphate rock containing between 400 and 600 mg Cd kg P. Pasture Cd uptake
      exacerbates the entry of Cd into animal products. We sought to determine the
      critical environmental factors affecting Cd uptake in NZ pastures and to
      calculate the likely Cd intake of sheep and cattle. We tested 69 pastures
      throughout NZ for a range of variables, including Cd. Soil Cd and pasture Cd were
      positively correlated with soil P and soil concentrations of other elements found
      in phosphate fertilizers. We found that no single environmental variable
      adequately predicted pasture Cd uptake. Nevertheless, pseudo-total soil Cd and Cd
      extracted using a 0.05 mol L Ca(NO) solution were positively correlated with
      pasture Cd. Although soil pH, soil Fe, and soil Cd provided an excellent
      predictor of the Ca(NO)-extractable soil Cd fraction, regression models explained
      just 38% of the variation of the Cd concentration in pasture grasses.
      Incorporating the effect of pasture species composition is a crucial next step in
      improving these models. A calculation of the likely exposure to Cd of sheep and
      cattle revealed that no pastures tested resulted in sheep and cattle ingesting Cd
      at a rate that would result in breaching muscle-tissue food standards. For offal
      products, which the NZ meat industry does not sell for human consumption, food
      safety standards exceedence was calculated in a few cases. 

PMID- 25602819
TI  - Integrated approaches of x-ray absorption spectroscopic and electron microscopic
      techniques on zinc speciation and characterization in a final sewage sludge
      product.
AB  - Integration of complementary techniques can be powerful for the investigation of
      metal speciation and characterization in complex and heterogeneous environmental
      samples, such as sewage sludge products. In the present study, we combined
      analytical transmission electron microscopy (TEM)-based techniques with X-ray
      absorption spectroscopy (XAS) to identify and characterize nanocrystalline zinc
      sulfide (ZnS), considered to be the dominant Zn-containing phase in the final
      stage of sewage sludge material of a full-scale municipal wastewater treatment
      plant. We also developed sample preparation procedures to preserve the organic
      and sulfur-rich nature of sewage sludge matrices for microscopic and
      spectroscopic analyses. Analytical TEM results indicate individual ZnS
      nanocrystals to be in the size range of 2.5 to 7.5 nm in diameter, forming
      aggregates of a few hundred nanometers. Observed lattice spacings match
      sphalerite. The ratio of S to Zn for the ZnS nanocrystals is estimated to be 1.4,
      suggesting that S is present in excess. The XAS results on the Zn speciation in
      the bulk sludge material also support the TEM observation that approximately 80%
      of the total Zn has the local structure of a 3-nm ZnS nanoparticle reference
      material. Because sewage sludge is frequently used as a soil amendment on
      agricultural lands, future studies that investigate the oxidative dissolution
      rate of ZnS nanoparticles as a function of size and aggregation state and the
      change of Zn speciation during post sludge-processing and soil residency are
      warranted to help determine the bioavailability of sludge-born Zn in the soil
      environment. 

PMID- 25602821
TI  - Forest Floor Lead Changes from 1980 to 2011 and Subsequent Accumulation in the
      Mineral Soil across the Northeastern United States.
AB  - Quantifying the transport rate of anthropogenic lead (Pb) in forest soils is
      essential for predicting air pollution impacts on northeastern United States soil
      quality. In 2011, we resampled the forest floor at 16 sites across the
      northeastern United States previously sampled in 1980, 1990, and 2002 and also
      sampled the upper two mineral soil horizons. The mean forest floor Pb
      concentration decreased from 151 +/- 29 mg kg in 1980 to 68 +/- 13 mg kg in 2011.
      However, the mean forest floor Pb amount per unit area remained similar (10 +/- 2
      kg ha in 1980 and 11 +/- 4 kg ha in 2011). Study sites were divided into three
      geographic regions: western, central, and northern. The modeled forest floor Pb
      response time (1/) was longer at frigid soil temperature regime sites (61 +/- 15
      yr) compared with mesic sites (29 +/- 4 yr). Mineral soil Pb concentration and
      amount were approximately four times greater at western and central sites
      compared with northern sites for both mineral horizons. Furthermore, mean isotope
      ratios of Pb/Pb (1.201 +/- 0.006) and Pb/Pb (2.060 +/- 0.021) indicated that Pb
      in the western and central forest floor and mineral soil was primarily gasoline
      derived. Our combined analytical approach using long-term forest floor monitoring
      and stable Pb isotopes suggest that the majority of anthropogenic Pb deposited on
      soils in the western and central sites has been transported to the mineral soil,
      whereas it continues to reside in the forest floor at northern sites. 

PMID- 25602822
TI  - Modeling spatial patterns in soil arsenic to estimate natural baseline
      concentrations.
AB  - Arsenic in soil is an important public health concern, but risk-based toxicity
      regulatory standards derived from laboratory studies should also consider
      concentrations measured away from obvious contamination (i.e., baseline
      concentrations that approximate natural background) to avoid unnecessary
      remediation burdens on society. We used soil and stream sediment samples from the
      USGS National Geochemical Survey to assess the spatial distribution of As over a
      1.16 * 10 km area corresponding to the state of Ohio. Samples were collected at
      348 soil and 144 stream sites at locations selected to minimize anthropogenic
      inputs. Total As was measured by sodium peroxide fusion with subsequent
      dissolution using concentrated HCl and analysis using hydride-generation atomic
      absorption spectrometry. Arsenic in the soil and streambed samples ranged from
      2.0 to 45.6 mg kg. Sequential Gaussian simulation was used to map the expected
      concentration of As and its uncertainty. Five areas of elevated concentration,
      greater than the median of 10 mg kg, were identified, and relationships to
      geologic parent materials, glacial sedimentation, and soil conditions
      interpreted. Arsenic concentrations <4 mg kg were rare, >10 mg kg common, and >20
      mg kg not unusual for the central and west central portions of Ohio.
      Concentrations typically exceeded the soil As human generic screening level of
      0.39 mg kg, a value corresponding to an increase in cancer risk of 1 in 1,000,000
      for soil ingestion. Such results call into question the utility of the USEPA and
      similarly low soil screening levels. The contrast between laboratory screens and
      concentrations occurring in nature argue for risk assessment on the basis of
      baseline concentrations. 

PMID- 25602823
TI  - Constraints on Precipitation of the Ferrous Arsenite Solid HFe(AsO).
AB  - Formation of Fe(II)-As(III) solids is suspected to limit dissolved As
      concentrations in anaerobic environments. Iron(II) precipitates enriched in
      As(III) have been observed after microbial reduction of As(V)-loaded
      lepidocrocite (gamma-FeOOH) and symplesite (Fe(II)(As(V)O)].8HO) and upon abiotic
      reaction of Fe(II) with As(III). However, the conditions favorable for Fe(II)
      As(III) precipitation and the long-term stability (relative to dissolution) of
      this phase are unknown. Here we examine the composition, local structure, and
      solubility of an Fe(II)-As(III) precipitate to determine environments where such
      a solid may form and persist. We reveal that the Fe(II)-As(III) precipitate has a
      composition of HFe(AsO) and a log of 34 for the dissolution reaction defined as:
      HFe(AsO) + 8H = 4Fe + 5HAsO. Extended X-ray absorption fine structure
      spectroscopic analysis of HFe(AsO) shows that the molecular environment of Fe is
      dominated by edge-sharing octahedra within an Fe(OH) sheet and that As is
      dominated by corner-sharing AsO pyramids, which are consistent with previously
      published structures of As(III)-rich Fe(II) solids. The HFe(AsO) solid has a pH
      dependent solubility and requires millimolar concentrations of dissolved Fe(II)
      and As(III) to precipitate at pH <7.5. By contrast, alkaline conditions are more
      conducive to formation of HFe(AsO); however, a high concentration of Fe(II) is
      required, which is unusual under alkaline conditions. 

PMID- 25602824
TI  - Differential Carbon and Nitrogen Controls of Denitrification in Riparian Zones
      and Streams along an Urban to Exurban Gradient.
AB  - Denitrification is an anaerobic microbial process that transforms nitrate (NO) to
      nitrogen (N) gas, preventing the movement of NO into coastal waters where it can
      lead to eutrophication. Urbanization can reduce the potential for denitrification
      in riparian zones and streams by altering the environmental conditions that
      foster denitrification (i.e., low oxygen and available C). Here we evaluated the
      factors limiting denitrification potential in forested and herbaceous riparian
      and stream pool and organic debris dam habitats in urban, suburban, exurban, and
      forested reference watersheds in the Baltimore, Maryland metropolitan area.
      Denitrification potential (with and without C and NO additions) and microbial
      biomass C and N content, potential net N mineralization and nitrification,
      microbial respiration, and inorganic N pools were measured in summer (June) and
      fall (November). Denitrification potentials were highest in the herbaceous
      riparian soils and lowest in pool sediments. Forested riparian soil
      denitrification potential was highest in the exurban watershed but in other
      habitats did not vary with watershed type. Nearly all variables were higher in
      June than in November. Overall, C was a more important driver of denitrification
      potential than N; potentials in unamended and N-amended treatments were very
      similar (<200 ng N g h) and were much lower than in the C-amended and C+N-amended
      treatments (>800 ng N g h). Our results suggest that efforts to enhance
      denitrification in urban watersheds need to focus on the differential controls of
      denitrification across habitats, urban land use types, and seasons. 

PMID- 25602825
TI  - Long-term Wastewater Irrigation Reduces Sulfamethoxazole Sorption, but Not
      Ciprofloxacin Binding, in Mexican Soils.
AB  - As a consequence of population growth and urbanization, arable fields are
      increasingly irrigated with wastewater, but the related environmental and health
      risks (e.g., pollution with antibiotics) are poorly understood. We performed
      batch sorption experiments with sulfamethoxazole (SMX) and ciprofloxacin (CIP)
      and soils that had been irrigated with untreated wastewater for 0, 14, 35, and
      100 yr. Sorption of CIP was always strong and largely irreversible irrespective
      of the duration of wastewater irrigation and the content and quality of soil
      organic matter (SOM) (Freundlich sorption coefficient, : 346-979 mg L kg; 1/:
      0.62-0.76) but decreased with increasing soil pH due to a decreasing fraction of
      the cationic species. Sorption of SMX and sorption hysteresis were stronger in
      the nonirrigated soil (: 4.14 mg L kg +/- 0.02; 1/: 0.69 +/- 0.02) than in the
      irrigated soils (: 0.65-1.38 mg L kg; 1/: 0.68-0.75). Irrigation (e.g.,
      competition with SMX accumulated in soil or with other organic compounds
      contained in wastewater) and SOM quality (i.e., increase of carboxylic moieties
      with increasing time of irrigation) had a stronger effect on SMX sorption and its
      hysteresis than soil organic carbon content. Whereas sorption of SMX can be
      reduced by long-term irrigation with wastewater, sorption of CIP is intense also
      after prolonged irrigation. 

PMID- 25602826
TI  - Greenhouse gas production in mixtures of soil with composted and noncomposted
      biochars is governed by char-associated organic compounds.
AB  - Biochar application to soil has the potential to increase soil productivity while
      reducing anthropogenic greenhouse gas (GHG) emissions to the atmosphere. However,
      techniques for conditioning this material for maximizing its effects as a soil
      amendment require elucidation. We examined changes of organic matter associated
      with two biochars after 175 d of composting and the resulting effects on GHG
      emissions during a 150-d incubation period. Composting decreased the amount of
      organic compounds that could be thermally released from the biochars and affected
      their molecular nature. These thermally desorbable organic compounds from initial
      biochars likely stimulated the oxidation of CH and inhibited the production of NO
      in soil-biochar mixtures. However, these reductions of GHG emissions disappeared
      together with thermally desorbable organic compounds after the composting of
      chars. Instead, addition of composted gasification coke and charcoal stimulated
      the formation of CH and increased NO emissions by 45 to 56%. Nitrous oxide
      emissions equaled 20% of the total amount of N added with composted biochars,
      suggesting that organic compounds and N sorbed by the chars during composting
      fueled GHG production. The transient nature of the suppression of CH and NO
      production challenges the long-term GHG mitigation potential of biochar in soil. 

PMID- 25602827
TI  - Soil, plant, and terrain effects on natural perchlorate distribution in a desert
      landscape.
AB  - Perchlorate (ClO) is a contaminant that occurs naturally throughout the world,
      but little is known about its distribution and interactions in terrestrial
      ecosystems. The objectives of this Amargosa Desert, Nevada study were to
      determine (i) the local-scale distribution of shallow-soil (0-30 cm) ClO with
      respect to shrub proximity (far and near) in three geomorphic settings (shoulder
      slope, footslope, and valley floor); (ii) the importance of soil, plant, and
      terrain variables on the hillslope-distribution of shallow-soil and creosote bush
      [ (Sesse & Moc. ex DC.) Coville] ClO; and (iii) atmospheric (wet plus dry,
      including dust) deposition of ClO in relation to soil and plant reservoirs and
      cycling. Soil ClO ranged from 0.3 to 5.0 MUg kg. Within settings, valley floor
      ClO was 17* less near shrubs due in part to enhanced leaching, whereas shoulder
      and footslope values were ~2* greater near shrubs. Hillslope regression models
      (soil, = 0.42; leaf, = 0.74) identified topographic and soil effects on ClO
      deposition, transport, and cycling. Selective plant uptake, bioaccumulation, and
      soil enrichment were evidenced by leaf ClO concentrations and Cl/ClO molar ratios
      that were ~8000* greater and 40* less, respectively, than soil values.
      Atmospheric deposition ClO flux was 343 mg ha yr, ~10* that for published
      southwestern wet-deposition fluxes. Creosote bush canopy ClO (1310 mg ha) was
      identified as a previously unrecognized but important and active reservoir.
      Nitrate deltaO analyses of atmospheric deposition and soil supported the leaf
      cycled-ClO input hypothesis. This study provides basic data on ClO distribution
      and cycling that are pertinent to the assessment of environmental impacts in
      desert ecosystems and broadly transferable to anthropogenically contaminated
      systems. 

PMID- 25602828
TI  - Does inorganic nitrogen fertilization improve soil aggregation? Insights from two
      long-term tillage experiments.
AB  - The relationship between inorganic fertilization and soil aggregation is not well
      understood. We studied cumulative nitrogen (N) fertilization impacts on
      aggregation, soil organic C (SOC), pH, and their relationships under irrigated
      and rainfed experiments in Nebraska after 27 and 28 yr, respectively. The
      dominant soil series were Crete silt loam at the irrigated site, and Coleridge
      silty clay loam at the rainfed site. We studied irrigated continuous corn ( L.)
      in chisel plow (CP) and ridge till (RidgeT) receiving 0, 75, 150, and 300 kg N ha
      yr and rainfed continuous corn and corn-soybean [ (L.) Merr.] in moldboard plow
      (MP), reduced till (RT), and no-till (NT) with corn receiving 0, 80, and 160 kg N
      ha yr. Fertilization altered soil aggregation in all tillage systems under
      continuous corn. Mean weight diameter of water-stable aggregates (MWDA) increased
      in the upper 7.5-cm depth in NT but decreased in the 7.5- to 60-cm depth by 1.5
      times with N application. Fertilization reduced pH but had little or no effect on
      SOC. Both MWDA and pH ( = 0.47***) decreased under irrigated corn, particularly
      in the 7.5- to 30-cm depth. No-till and RT had two to five times greater near
      surface MWDA than MP. Continuous corn had greater MWDA than corn-soybean in the
      upper 30-cm depth except in MP. Long-term N fertilization improves near-surface
      soil aggregation in NT continuous corn but reduces aggregation in the subsoil.
      Results also suggest that, if fertilizers are applied at rates of about 80 kg N
      ha, deterioration of soil aggregation would be minimal. 

PMID- 25602829
TI  - A Comparison of Fish-based Classification Schemes for Reference Streams and
      Rivers in Nebraska.
AB  - Proper assessments of lotic ecosystems depend on our ability to isolate natural
      differences from anthropogenic disturbances. We examined Nebraska river and
      stream classification strength, based on fish species, using multiple response
      permutation procedures for common classification strategies: ecoregions,
      watersheds, hydrologic-landscape regions, and assemblage structure from cluster
      analyses. Next, we tested the ecological interpretability of classification
      schemes using nonmetric multidimensional scaling ordinations and ANOVAs. Finally,
      we used nonparametric ANOVA to identify environmental predictors of overall fish
      assemblage structure. Hydrologic-landscape regions had the highest classification
      strength, but cluster groups had the most ecological interpretability based on
      the discreteness of the groups in ordination space and on the large number of
      common species that had different abundances across cluster groups. In addition,
      presence/absence data provided groups with more classification strength and
      interpretability than abundance data. Temperature, stream size, total phosphorus
      concentrations, and the percentage of fine substrates were significantly
      correlated to nonmetric multidimensional scaling ordinations and to overall fish
      structure in the multivariate ANOVA models. Cluster analyses using
      presence/absence were therefore the best classification scheme, and we identified
      the environmental variables that are likely to be useful for determining whether
      streams should have similar biotic assemblages. This information will be a
      valuable guide for separating natural variability in biotic assemblages from
      anthropogenic influences. 

PMID- 25602830
TI  - Measurement and Modeling of Denitrification in Sand-Bed Streams under Various
      Land Uses.
AB  - Although many studies have measured denitrification in stream sediments, few have
      utilized these data with local water column and sediment measurements to develop
      a predictive model for NO uptake. In this study, sediment denitrification was
      measured from cores in five streams under various land uses in south-central
      Minnesota using denitrification enzyme activity (DEA) assays and amplification of
      the gene via real-time, quantitative polymerase chain reaction. Hydraulic and
      environmental variables were measured in the vicinity of the sediment cores to
      evaluate the influence of fluid flow and chemical variables on denitrification
      activity. Potential denitrification rates measured using DEA assays ranged from
      0.02 to 10.1 mg N m h, and the abundance of the denitrifier gene was positively
      correlated with these measurements ( = 0.79, < 0.001) for most of the streams
      studied. A predictive model to determine NO uptake via denitrification was
      derived, implementing dimensional analysis of variables that mediate
      denitrification in sand-bed streams. The proposed model explained 75% of the
      variability in DEA rates. The results of this study show that denitrification is
      most dependent on the distribution of sediment organic matter, interstitial pore
      space, and stream hydraulic characteristics, including shear velocity at the
      sediment-water interface and stream depth. 

PMID- 25602831
TI  - Fertilization strategies affect phosphorus forms and release from soils and
      suspended solids.
AB  - The release of phosphorus from soils in surface runoff is strongly influenced by
      fertilizer inputs and contributes significantly to agriculturally driven
      eutrophication. This work evaluated the forms and availability of P in bulk soils
      and suspended solids (SS) produced by a water dispersion test that mimics the
      action of rain events and/or irrigation. This test was applied on soils
      cultivated with maize and fertilized with mineral N, P, and K (NPK); mineral P
      and K (PK); bovine slurry and P (S); or manure and P (M) for 15 yr. The P surplus
      in the treated soils was in the order NPK < PK < S < M. Forms and availability of
      P were analyzed in bulk soils, and their respective SS (<20 MUm) by the Hedley
      sequential P fractionation method and the isotopic exchange kinetics. The labile
      forms increased according to P surplus and represented up to 15 and 25% of total
      P in the bulk soil and in the SS, respectively, indicating a selective enrichment
      of the more labile P forms in the erodible particles. Exchangeability of P from
      SS was rapid and intense as a result of a shift of P solution equilibrium at the
      increased water/solid ratio and a larger accumulation of more labile P in the
      detached particles than in the bulk soil. Phosphorus saturation of iron and
      aluminum oxides and the enrichment of fertilizer-derived P salts in the suspended
      solids control P forms and exchangeability for mineral fertilizer treatments,
      whereas in M soil carbon content assumed a key role. 

PMID- 25602832
TI  - Investigation of ammonium ion removal from aqueous solutions using arene- and
      propylsulfonic Acid functionalized mesoporous silica adsorbents.
AB  - To counter environmental threats to the water resources polluted by NH, which is
      common in wastewaters and agricultural runoff, adsorption using mesoporous
      functional materials represents a promising alternative to existing treatment
      methods. In this study, adsorption of NH ions from aqueous solutions was
      investigated on arene- and propylsulfonic acid functionalized SBA-15 mesoporous
      silica materials. The adsorbents were synthesized via co-condensation and post
      synthesis grafting procedures. Adsorbents were characterized by means of X-ray
      diffraction, N physisorption, titration, and elemental analyses. The effects of
      pH, NH initial concentration, temperature, adsorbent loading, organosilane molar
      ratio, and presence of competitive species on the performance of the adsorbent
      materials were examined. All the adsorbents having an organosilane/silica molar
      ratio of 1:5 displayed maximum adsorption capacity around approximately 25 mg g
      NH at the lowest temperature investigated, 5 degrees C. This capacity decreased
      with increasing temperature. For a given initial NH concentration, the removal
      efficiency () increased with increasing adsorbent loading. For instance,
      increased from 24 to 59% when the adsorbent loading was increased from 2 to 10 g
      L at 25 degrees C. The adsorption isotherms were well described by a Langmuir
      model equation. Adsorption capacity improved with increasing organosilane/silica
      molar ratio, reaching 42 mg g NH with a ratio of 2:5 at 25 degrees C. Arene- and
      propylsulfonic acid functionalized SBA-15 materials synthesized via co
      condensation and post-synthesis grafting proved to be effective high-capacity
      adsorbents for the removal of NH ions from aqueous solutions. 

PMID- 25602833
TI  - Effect of Livestock Slurry Ozonation and Separation on pH, Particles, and
      Phosphate.
AB  - Applying slurry to arable land as fertilizer increases the risk of phosphorus (P)
      runoff and thereby increases the risk of eutrophication. Solid-liquid separation
      can reduce the excess application of P, and this study focused on the use of
      ozonation as an alternative chemical pretreatment for separation to improve P
      separation efficiency. Sow and cattle slurries were separated by screw press and
      flocculation+filtration. The screw press and flocculation liquid fractions and
      raw slurries were treated with no ozone or with low-, medium-, or high-ozone
      doses and then separated by centrifugation. The pH, particle size distribution,
      dry matter, and dissolved phosphate (PO) concentrations were measured. For
      separations without ozonation, pH increased by 0.15 to 0.87 pH units, and
      correlation analysis showed that the dissolved PO concentration decreased with
      increasing pH and particle removal efficiency. During ozonation, pH increased,
      and a shift in particle size distribution in the liquid fraction combined with an
      improved dry matter separation indicated particle aggregation. Ozonation thus
      affected the parameters found to affect dissolved PO separation, and at the
      highest ozone dose, dissolved PO separation efficiency increased by 7 to 81%. An
      ozonation pretreatment may therefore promote removal of dissolved PO from the
      liquid fraction during separation. 

PMID- 25602834
TI  - The molecular environment of phosphorus in sewage sludge ash: implications for
      bioavailability.
AB  - Producing a P fertilizer from sewage sludge ash (SSA) is a strategy to
      efficiently recycle P from a secondary raw material. The P speciation in four
      SSAs was characterized before and after the removal of heavy metals by a thermo
      chemical treatment that involved CaCl addition. We chose complementary techniques
      to determine the direct P speciation, including X-ray powder diffraction, solid
      state P direct-polarization magic-angle spinning nuclear magnetic resonance, and
      X-ray absorption near edge structure. Results from these techniques were compared
      with operational and functional speciation information obtained from a sequential
      P extraction and a plant biotest with Italian ryegrass grown on a soil-sand
      mixture with little available P. The speciation of P in untreated and thermo
      chemically treated SSAs depended on their elemental composition. At a molar ratio
      of Ca:P <= 2, SSAs contained combinations of polymorphs of AlPO, beta-tricalcium
      phosphate, and apatite-like P species. In SSAs with a molar ratio of Ca:P > 2, an
      apatite-like molecular environment was predominant. The thermo-chemical process
      induced an increase in crystalline phases and enhanced the crystallinity of the P
      species. The structural order of the bulk sample was the most decisive parameter
      in controlling the P availability of the studied SSAs to plants. We conclude
      that, to produce a high-quality fertilizer and despite of the successful heavy
      metal removal, the thermo-chemical process requires further development toward
      enhanced P bioavailability. 

PMID- 25602835
TI  - Dissipation of Three Veterinary Antimicrobials in Beef Cattle Feedlot Manure
      Stockpiled over Winter.
AB  - Dissipation of veterinary antimicrobials is known to occur during aerated windrow
      composting of beef cattle manure. However, it is unclear if a similar dissipation
      occurs during stockpiling. Chlortetracycline, tylosin, and sulfamethazine are
      three of the most commonly used veterinary antimicrobials in beef cattle
      production in western Canada. Their dissipation in stockpiled manure was
      investigated over 140 d during winter in Alberta, Canada. Beef cattle housed in
      pens were administered 44 mg of chlortetracycline kg feed (dry weight), 44 mg of
      chlortetracycline + 44 mg sulfamethazine kg feed, 11 mg of tylosin kg feed, or
      feed without antimicrobials (control). Manure samples were extracted using
      pressurized liquid extraction, and the extracts were analyzed for
      chlortetracycline, sulfamethazine, and tylosin by LC-MS-MS. Dissipation of all
      three antimicrobials in the manure was explained by exponential decay kinetics.
      Times for 50% dissipation (DT) were 1.8 +/- 0.1 d for chlortetracycline alone or
      6.0 +/- 0.8 d when mixed with sulfamethazine, 20.8 +/- 3.8 d for sulfamethazine,
      and 4.7 +/- 1.2 d for tylosin. After 77 d, <1% of initial chlortetracycline and
      <2% of sulfamethazine remained. Tylosin residues were more variable, decreasing
      to approximately 12% of initial levels after 28 d, with 20% present after 77 d
      and 13% after 140 d. Temperatures within stockpiles reached maximum values within
      6 d of establishment and varied with location (bottom, 62.5 degrees C; middle,
      63.8 degrees C; and top, 42.9 degrees C). Antimicrobials in the manure did not
      inhibit microbial activity, as indicated by temperature and mass losses of carbon
      (C) and nitrogen (N). The C/N ratio in the manure decreased over the stockpiling
      period, indicating decomposition of manure to a more stable state. Dissipation of
      excreted residues with DT values 1.8 to 20.8 d showed that stockpiling can be as
      effective as windrow composting in mitigating the transfer of these three
      veterinary antimicrobials into the environment during land application of
      processed manure. 

PMID- 25602836
TI  - Phosphorus removal in a surface-flow constructed wetland treating agricultural
      runoff.
AB  - Agricultural runoff is a leading source of phosphorus (P) pollution to lakes and
      streams. The objective of this study was to evaluate P removal dynamics in a
      constructed treatment wetland (CTW) treating agricultural irrigation return
      flows. The CTW included a sedimentation basin (SB) followed by two surface-flow
      wetlands in parallel. Typical retention times and total P (TP) loading were 1.4 d
      and 50 to 110 g m yr P, respectively, for the SB and 5 to 6 d and 4 to 10 g m yr
      P, respectively, for wetlands. On the basis of this multiyear study,
      concentration removal efficiency in the SB averaged 21% for TP and 32% for
      reactive phosphorus (RP). Concentration removal efficiency in wetlands averaged
      37 and 43% for TP and 22 and 33% for RP. Areal first-order removal rates for TP
      averaged 22 and 31 m yr in wetlands. Total P removal in wetlands exhibited a
      strong seasonal pattern, with minimum removal in the summer when high
      temperatures likely enhanced P release from decaying plant biomass. The
      performance of the CTW was stochastic, with removal unpredictably poorer in some
      years in part as a result of muskrat bioturbation and plant harvesting. In years
      before muskrat impacts, concentration removal efficiencies in wetlands were 50%
      for TP and 65% for RP. 

PMID- 25602838
TI  - Acs324.1 editorial board.

PMID- 25602837
TI  - Evaluation and application of a paper-based device for the determination of
      reactive phosphate in soil solution.
AB  - The evaluation and validation of a new low-cost microfluidic paper-based
      analytical device (MUPAD) for the determination of reactive phosphate in soil
      solution is described. This device allows up to 15 replicate measurements of
      reactive phosphate on one credit card-sized device and requires only a desktop or
      hand scanner for signal detection and quantification. The proposed method showed
      a linear response between 0.1 and 1.0 mg L and between 1.0 and 10.0 mg L P with a
      limit of detection of 0.05 mg L P. When applied to the analysis of soil solution,
      there was excellent agreement between results obtained using the MUPAD and those
      obtained by a reference spectrophotometric method, as indicated by the following
      regression equation: [P] = (0.997 +/- 0.005)[P] - (0.020 +/- 0.008) ( = 0.997; =
      110). It was found that the ambient temperature storage stability of the MUPAD
      could be extended to 15 d by incorporating a removable polymeric interleaving
      sheet between the adjacent paper layers of the device. The observed sensitivity
      of the MUPADs to sunlight, which was manifested by photoreduction of the
      chromogenic molybdate reagent used in the assay, was overcome by preparing the
      MUPADs with an ultraviolet-filtering laminating material. The proposed method is
      rapid, with a reaction time of only 10 min, is easy to perform, and is suitable
      for application in the field. 

PMID- 25602840
TI  - Residents' scholarly activity: a cost analysis with regard to its effects on
      departments.
AB  - PURPOSE OF REVIEW: Current financial strain on training departments may have a
      significantly negative impact on continuing support for residents' scholarly
      activity. A cost analysis with regard to residents' scholarly activity effects on
      anesthesiology training departments is performed. RECENT FINDINGS: The
      Accreditation Council for Graduate Medical Education has issued a new outcome
      focused scholarly activity requirement. Low scholarly achievement by
      anesthesiology faculty in the USA has been documented and needs transformation.
      It is evident that a structured scholarly activity support system is effective.
      To support such a system, training departments need to support anesthesiology
      residents' nonclinical time, which would cost an average of $13,500 per month per
      resident using nonresident hands-on care providers in operating rooms, resident's
      meeting attendance in average $1,424 per resident per meeting, and faculty
      mentorship and other infrastructure. It must also be taken into account that
      missed clinical opportunities by an anesthesiology resident during nonclinical
      time are an estimated average of 60 cases per month. SUMMARY: The importance of
      resident scholarly activity has never been so or as critical as in the present.
      Anesthesiology leadership must continue to invest to support resident scholarly
      activity for the future of the specialty while being mindful of costs incurred.

PMID- 25602841
TI  - Modulation doping of GaAs/AlGaAs core-shell nanowires with effective defect
      passivation and high electron mobility.
AB  - Reliable doping is required to realize many devices based on semiconductor
      nanowires. Group III-V nanowires show great promise as elements of high-speed
      optoelectronic devices, but for such applications it is important that the
      electron mobility is not compromised by the inclusion of dopants. Here we show
      that GaAs nanowires can be n-type doped with negligible loss of electron
      mobility. Molecular beam epitaxy was used to fabricate modulation-doped GaAs
      nanowires with Al0.33Ga0.67As shells that contained a layer of Si dopants. We
      identify the presence of the doped layer from a high-angle annular dark field
      scanning electron microscopy cross-section image. The doping density, carrier
      mobility, and charge carrier lifetimes of these n-type nanowires and nominally
      undoped reference samples were determined using the noncontact method of optical
      pump terahertz probe spectroscopy. An n-type extrinsic carrier concentration of
      1.10 +/- 0.06 * 10(16) cm(-3) was extracted, demonstrating the effectiveness of
      modulation doping in GaAs nanowires. The room-temperature electron mobility was
      also found to be high at 2200 +/- 300 cm(2) V(-1) s(-1) and importantly minimal
      degradation was observed compared with undoped reference nanowires at similar
      electron densities. In addition, modulation doping significantly enhanced the
      room-temperature photoconductivity and photoluminescence lifetimes to 3.9 +/- 0.3
      and 2.4 +/- 0.1 ns respectively, revealing that modulation doping can passivate
      interfacial trap states.

PMID- 25602842
TI  - High-performance, room-temperature, and no-humidity-impact ammonia sensor based
      on heterogeneous nickel oxide and zinc oxide nanocrystals.
AB  - NiO nanocones decorated with ZnO nanothorns on NiO foil substrates are shown to
      be an ammonia sensor with excellent comprehensive performance, which could, in
      real-time, detect and monitor NH3 in the surrounding environment. Gas-sensing
      measurements indicate that assembling nanocones decorated with nanothorns on NiO
      foil substrate is an effective strategy for simultaneously promoting the
      stability, reproducibility, and sensitivity of the sensor, because the NiO foil
      substrate as a whole can quickly and stably transfer electrons between the gas
      molecules and the sensing materials and the large specific surface area of both
      nanocones and nanothorns provide good accessibility of the gas molecules to the
      sensing materials. Moreover, p-type NiO, with majority charge carriers of holes,
      has higher binding affinity for the electron-donating ammonia, resulting in a
      significant increase in selectivity toward NH3 over other organic gases. Compared
      with the NiO nanowires and pure NiO nanocones, the heterogeneous NiO
      nanocones/ZnO nanothorns exhibit less dependence on the temperature and humidity
      in response/recovery speed and sensitivity of sensing NH3. Our investigation
      indicates that two factors are responsible for reducing the dependence on the gas
      sensing characteristics under various environmental conditions. One is that the n
      type ZnO nanothorns growing on the surface of nanocones, with majority charge
      carriers of electrons, speed up adsorption and desorption of gas molecules. The
      other is that the abundant cone-shaped and thornlike superstructures on the
      substrate are favorable for constructing a hydrophobic surface, which prevents
      the gas sensing material from being wetted. 

PMID- 25602843
TI  - Using "Rebar" to Stabilize Rigid Chest Wall Reconstruction.
AB  - After major chest wall resection, reconstruction of the bony defect with a rigid
      prosthesis is mandatory to protect the underlying thoracic organs, and to prevent
      flail chest physiology. Although many methods have been described for chest wall
      reconstruction, a commonly used technique employs a composite Marlex
      (polypropylene) mesh with methyl-methacrylate cement sandwiched between two
      layers of mesh (MMS), which is tailored to the defect size and shape. In building
      construction, steel "rebar" is used to strengthen and reinforce masonry
      structures. To avoid the initial residual motion of the rigid prosthesis used to
      reconstruct very large defects, particularly the sternum, we devised a simple
      technique of adding one or more Steinmann steel pins as "rebar" to strengthen and
      immediately stabilize the prosthesis to the surrounding ribs and sternum. For the
      very large defects, particularly over the heart and great vessels, titanium mesh
      may also be readily added into the sandwich construction for increased strength
      and to prevent late prosthetic fractures. Short- and long-term results of this
      inexpensive modification of the MMS reconstruction technique are excellent. This
      modified MMS tailor-made prosthesis is only one-third the cost of the recently
      popular prosthetic titanium systems, takes much less operative time to create and
      implant, and avoids the well-described complications of late titanium bar
      fracture and erosion/infection as well as loosening of screws and/or titanium
      bars. 

PMID- 25602844
TI  - First clinical experience with the Innova versus the Protege EverFlex self
      expanding bare metal stents in superficial femoral artery occlusions.
AB  - BACKGROUND: To evaluate outcomes of superficial femoral artery (SFA) stenting
      with Boston Scientific Innova stent system (Boston Scientific Corporation Place,
      Natick, Massachusetts, United States) compared with ev3 Protege stent system
      (Endovascular, Inc., Plymouth, Minnesota, United States) in terms of safety and
      effectiveness and to identify factors predictive of restenosis. METHODS: From
      March 2012 to January 2013, 71 patients with SFA TASC (Trans Atlantic Inter
      Societal Consensus)-II B and C occlusive lesions were treated by percutaneous
      transluminal angioplasty with stenting (30 patients in the Innova group and 41
      cases in the Protege group) and were evaluated by retrospective observational
      data analysis. Chi-square tests for categorical data and time to event provided
      two-sided p values with a level of significance at 0.05 and 95% confidence
      intervals (CIs). Survival curves for primary patency were plotted using the
      Kaplan-Meier method. Univariate analysis for diabetes, hypercholesterolemia,
      smoking, hypertension, and critical limb ischemia was performed according to the
      Cox proportional hazards model. RESULT: The mean follow-up was 14 months (range 1
      18 months). The occlusive lesions treated were <=15 cm in length. The 12-month
      primary patency rate was significantly higher in the Protege group (81.5%; 31/38)
      than the Innova group (43.3%; 13/30; hazard ratio [HR] 3.0; 95% CI: 1.38-6.8; p =
      0.005. The secondary patency was similar to the primary comparison data and
      showed a significant advantage for the Protege stent (HR 2.9; 95% CI: 1.21-6.99;
      p = 0.01). Univariate analysis demonstrated that diabetes and smoking were
      significantly related to patency failure in both groups. CONCLUSIONS: SFA
      stenting is generally a safe procedure, but the effectiveness and patency rates
      are significantly lower for Innova than Protege. Furthermore, preoperative
      diabetes and smoking continue to be associated with low primary patency rate.
      These preliminary data suggest that Innova stent is not the treatment of choice
      for SFA lesions.

PMID- 25602845
TI  - Acute Compartment Syndrome of the Lower Leg after Coronary Artery Bypass
      Grafting: A Silent but Dangerous Complication.
AB  - BACKGROUND: Acute compartment syndrome (ACoS) is a serious, limb-threatening
      condition, but ACoS after coronary artery bypass grafting (CABG) is rare. ACoS is
      diagnosed with the help of typical symptoms, but due to the use of analgesics in
      a postoperative setting, these symptoms may vary. Identifying risk factors for
      ACoS after CABG could reduce the risk of developing this complication. METHODS:
      We describe the clinical presentation, diagnosis, and management of five cases of
      ACoS arising from CABG procedures at our institution during the last 5 years. We
      also review all cases found in literature about this complication. DISCUSSION:
      Both systemic and local factors may contribute to ACoS of the lower leg. These
      factors include increased microvascular permeability caused by cardiopulmonary
      bypass (CPB), the use of cardiac-assist devices causing arterial occlusion and
      reperfusion injury, diminished arterial blood flow in patients with peripheral
      vascular disease due to lithotomy position and the use of elastic bandages and
      local trauma and hematoma formation due to the harvesting of the greater
      saphenous vein (GSV). CONCLUSION: To prevent this serious complication, we advise
      to pay extra attention to the patients with a greater risk. Hemostasis after
      venectomy in CABG surgery is mandatory, especially in the endoscopic harvesting
      of the GSV. Elastic bandages should be applied after weaning from CPB. Elevated
      creatine phosphokinase values may indicate ACoS. When suspicion arises,
      intracompartmental pressure measurement is the preferred tool for early
      recognition and diagnosis. To prevent irreversible, extensive tissue damage and
      permanent disability fasciotomy must be performed immediately after the diagnosis
      is made.

PMID- 25602846
TI  - A Cross-Sectional Study of Chest Wall Development in Patients with Pectus
      Excavatum.
AB  - BACKGROUND: We conducted a cross-sectional study to quantify the developmental
      changes of the thoracic cage in patients with pectus excavatum (PE). METHODS: The
      preoperative posteroanterior standing chest radiographs (chest PAs) of 1,197
      consecutive patients with PE, together with 1,661 age- and sex-matched minor
      surgery patients, as a control group, who were seen between June 2005 and
      February 2013, were reviewed. The maximum width of each rib pair and chest height
      (H) were measured on the chest PA. RESULTS: In the PE group, the normal thoracic
      contour in younger patients was replaced by a characteristic can-shaped chest
      wall, which showed protrusion of the upper ribs, an increased H, and a
      straightened lateral border of the chest cage, as they grew into adulthood. The
      chest height difference between the PE and control groups increased
      progressively, from the age of 8 years and most significantly from age 13 to 17
      years. No difference was observed in the middle and lower rib widths. Sex did not
      influence these trends. CONCLUSION: The PE chest wall shows a significant
      increment in chest height, and upper rib width starts during the period of rapid
      growth and is maintained into adulthood. The thoracic deformity in patients with
      PE includes more than just the sternal deformity.

PMID- 25602847
TI  - When Is the Optimal Timing of the Surgical Treatment for Secondary Spontaneous
      Pneumothorax?
AB  - Objectives The definition of spontaneous pneumothorax is accumulation of air in
      the pleural space, resulting in dyspnea or chest pain. Unlike primary spontaneous
      pneumothorax, secondary pneumothorax can be a life-threatening condition and
      spontaneous healing rate is uncommon. Although surgery is the most effective
      treatment modality for pneumothorax, surgical management and timing is difficult
      where there is underlying lung disease and/or medical comorbidities. Prolonged
      air leakage increases the morbidity and mortality in thoracic surgery. We
      hypothesized that duration of air leakage before operation may lead to increase
      in complications. Methods This study is a retrospective review of 155 consecutive
      patients with air leakage who underwent bullectomy for secondary spontaneous
      pneumothorax from January 2005 to July 2013. The patients were divided according
      to the duration of preoperative air leakage. The patients were followed-up until
      the time of last visit or death. Postoperative morbidity and mortality were
      assessed and the risk factors for complications were analyzed. Results The median
      age was 65 years (range, 52-88) with male predominance (96.13%). The median
      duration of preoperative air leakage was 6 days (range, 1-30). The median surgery
      time was 90 minutes (range, 25-300) and median hospital stay after operation was
      7 days (range, 3-75). Postoperative complications occurred in 38 patients
      (24.52%) and postoperative recurrence was shown to have occurred in 8 patients
      (5.16%). With multivariate analysis, risk factors for postoperative complications
      were: underlying interstitial lung disease and air leakage > 5 days before
      operation. Conclusion Persistent air leakage was a major surgical indication for
      pneumothorax. Early surgical treatment reduced postoperative complications for
      secondary spontaneous pneumothorax.

PMID- 25602848
TI  - Controlled-Release Oxycodone as "Gold Standard" for Postoperative Pain Therapy in
      Patients Undergoing Video-Assisted Thoracic Surgery or Thoracoscopy: A
      Retrospective Evaluation of 788 Cases.
AB  - BACKGROUND: To assess the clinical efficacy of controlled-release oxycodone for
      postoperative analgesia after video-assisted thoracic surgery (VATS) or
      thoracoscopy. METHODS: Pain therapy is standardized in our thoracic center
      throughout the complete postoperative stay. Patients receive immediately
      postoperative standardized oral analgesic protocol with controlled-released
      oxycodone (Oxy Group) or oxycodone with naloxone (Targin Group) and nonopioid
      every 6 h. We switched the opioid protocol from controlled-release oxycodone to
      Targin in January 2012. All patients are visited daily by a pain specialist
      throughout the whole stay. RESULTS: Data of 788 patients undergoing VATS (n =
      367) or thoracoscopy (n = 421) during January 2011 until March 2013 were
      analyzed. In VATS, patients with Targin had higher pain scores at rest (p < 0.02)
      and on coughing (p < 0.001) than patients with oxycodone alone and more patients
      with Targin were dismissed with oral opioid dose than patients with oxycodone
      alone (p < 0.001). No differences in pain scores on POD 5 and 6, or in length of
      hospital stay, incidence of nausea, time to first dejection or opioid dose after
      dismission were found between controlled-release oxycodone and Targin. After
      conventional thoracoscopy, 209 patients received controlled-release oxycodone and
      212 Targin. Patients with Targin had higher pain scores at rest (p < 0.004) and
      on coughing (p < 0.01) than patients with oxycodone alone and more patients with
      Targin were dismissed with oral opioid dose than patients with oxycodone alone (p
      < 0.004). There were no differences in pain scores on POD 5 and 6, or in length
      of hospital stay, incidence of nausea, time to first dejection or opioid dose
      after dismission. CONCLUSION: Oral opioid analgesia with controlled-release
      oxycodone is an effective postoperative regimen after VATS and thoracoscopies.
      Our retrospective data indicate that Targin might be less effective analgesic
      than oxycodone after VATS and thoracoscopies with no improvement in bowel
      function in the immediate postoperative period. STUDY LIMITATIONS: The study
      design is retrospective in nature.

PMID- 25602849
TI  - Experience with Vacuum-Assisted Closure in the Management of Postpneumonectomy
      Empyema: An Analysis of Eight Cases.
AB  - BACKGROUND: The treatment of postpneumonectomic empyema is challenging. The aim
      of this study was to test the efficacy of vacuum-assisted closure (VAC) in the
      treatment of patients with open window thoracostomy (OWT). METHODS: Between
      January 2010 and April 2014, eight patients developed empyema following
      pneumonectomy for malignant diseases in our department and then underwent an OWT
      with subsequent VAC therapy; their cases were retrospectively studied. Each
      session of VAC therapy lasted 72 hours, and therapy was completed after
      approximately 6 sessions. RESULTS:  OWT in six patients resulted in either
      decreased size or complete closure after VAC treatment. Five patients had a
      bronchopleural fistula (BPF), which was closed either with a tracheal stent
      (three patients), primary suture, or omentoplasty. The BPF in one of these
      patients closed during VAC therapy. The treatment failed in two patients due to
      the microfistula becoming obvious in one and persistence of the fistula in the
      other. CONCLUSION:  We believe that the use of VAC in the treatment of
      postpneumonectomy empyema is effective, except for patients with BPF.

PMID- 25602850
TI  - Single-Port Video-Assisted Thoracoscopic Major Lung Resections: Experience with
      150 Consecutive Cases.
AB  - Background Video-assisted thoracic surgery (VATS) for major lung resection has
      undergone major changes from three or four-port approach to the recently possible
      single-port VATS approach. Outcomes following single-port VATS major lung
      resection are analyzed to determine safety and efficacy. Methods A prospective
      database of 150 consecutive patients who underwent single-port VATS major lung
      resection between March 2012 and January 2014 was reviewed. Patient demographics,
      perioperative parameters, histopathology, and outcomes up to follow-up of 2 years
      were analyzed by descriptive and Kaplan-Meier survival statistics. Results Single
      port VATS major lung resection was successfully performed in 142 patients
      (conversion rate 5.3%) for both malignant and benign diseases of the lung.
      Overall, 130 patients (87%) had nonsmall-cell lung carcinoma (NSCLC), 9 (6%) had
      other types of primary lung cancer, and the remaining for secondary malignancies
      and benign diseases. Among the 130 patients with NSCLC, 93 (71.5%) were stage I,
      28 were stage II (21.5%), and 9 (7%) were stage III or greater. There was no
      intraoperative or 30-day mortality. However, one perioperative death occurred on
      day 49, and another on day 60 postoperatively due to infective causes. The
      overall 2-year mortality rate for all patients was 3%. The disease-free survival
      rate for subgroups, stage I NSCLC, and stage II or greater NSCLC were 96 and 83%,
      respectively. Conclusions Single-port VATS major lung resection for malignant and
      benign lung diseases is associated with low perioperative morbidity and
      mortality. Disease-free survival rates for NSCLC are acceptable and comparable
      with conventional VATS. 

PMID- 25602851
TI  - Unilateral Sympathectomy for Primary Palmar Hyperhidrosis.
AB  - BACKGROUND AND OBJECTIVE: Primary palmar hyperhidrosis that arises mostly during
      puberty and early adolescence has a tremendous impact on the quality of life in
      patients. This study aimed to investigate the effectiveness of unilateral video
      assisted thoracic sympathectomy for dominant hand in these patients. PATIENTS AND
      METHODS: From July 2010 to June 2013, 52 patients with primary palmar
      hyperhidrosis underwent unilateral video-assisted thoracoscopic sympathectomy for
      dominant hand. We analyzed the outcomes regarding the resolution of symptoms,
      occurrence of complications, recurrence rate, and compensatory hyperhidrosis, and
      need of operation for opposite side. FINDINGS: All patients were followed up from
      6 to 42 months. Palmar hyperhidrosis was completely alleviated and absolute
      dryness was achieved in all patients at the same hand after the operation. Palmar
      hyperhidrosis in the opposite hand was cured to a complete dryness in 24 (46.15%)
      patients. No change happened in the opposite hand in 22 (42.3%) patients, but an
      increase was seen in 6 (11.53%) patients. Only seven (13.46%) patients needed to
      undergo contralateral sympathectomy. Compensatory hyperhidrosis occurred in 13
      patients (25%) after unilateral sympathectomy. Another five patients (totally 18,
      34.6%) were involved with compensatory hyperhidrosis after contralateral
      sympathectomy. It was mainly on the trunk in all 18 patients. CONCLUSION:
      Unilateral dominant side thoracoscopic sympathectomy for patients with primary
      palmar hyperhidrosis is an effective, safe, and minimally invasive procedure.
      Only a small number of patients will eventually require a contralateral
      sympathectomy in nondominant hand.

PMID- 25602852
TI  - Curcumin induces glioma stem-like cell formation.
AB  - In recent times, dozens of articles have been rushing to report the excellent
      performance of curcumin in inhibiting the proliferation of glioma cells and in
      inducing apoptosis and autophagy. However, in this study, we found that curcumin
      could not only effectively inhibit the proliferation of glioma cells but also
      induce glioma cells to be stem-like, which showed that it caused some glioma
      cells to form spheres with CD133 and Nestin positive markers. Further research on
      its underlying mechanism showed that curcumin suppressed transition of the cells
      from G1 to S phase and enhanced the expression of Sox4, Sox2, and Oct4, which
      were essential to retain the stemness properties of glioma-initiating cells. In
      conclusion, we believe these findings can complement our knowledge on curcumin
      and arouse our attention to use curcumin for further research on glioma
      treatment. 

PMID- 25602853
TI  - Left hemispheric contributions to temporal perception: a resting
      electroencephalographic study.
AB  - Beta brain wave frequencies, theta brain wave frequencies, and interhemispheric
      transfer rates were investigated in individuals to explore components of time
      perception. Research suggests that the left hemisphere is highly involved in
      attention and language, which are important components of temporal processing
      mechanisms. Resting state electroencephalography was used to evaluate the
      relationship between right and left hemispheric brain wave frequencies and
      performance on a duration-discrimination task and an interhemispheric transfer
      rate task. A stepwise multiple regression was used to investigate the absolute
      spectral power of right minus left hemispheric activation for each frequency
      (alpha, beta, gamma, theta) at each of eight paired electrode locations onto d'
      data for a temporal discrimination task. Higher absolute spectral power in
      parietal and temporal left electrodes was predictive of better performance on the
      duration-discrimination task. Right-to-left interhemispheric transfer approached
      a significant correlation with performance on the duration-discrimination task.
      Our results indicate that sensitivity on a temporal task is positively correlated
      with beta and theta brain wave frequencies, and negatively correlated with right
      to-left interhemispheric transfer rates. The current study provides support for a
      left hemispheric advantage for temporal processing; this provides further
      explanation of temporal processing mechanisms and where deficits may occur in
      clinical populations. 

PMID- 25602854
TI  - Impact of cardiac magnetic resonance on endothelial function in type 2 diabetic
      patients.
AB  - OBJECTIVES: Recent studies have shown that cardiac magnetic resonance (CMR)
      scanning is associated with cellular DNA damage. The aim of the present study was
      to assess the impact of CMR scanning on endothelial function in Chinese men with
      type 2 diabetes. METHODS: A randomized, single-blind, parallel-group study was
      conducted in 60 Chinese men with type 2 diabetes treated with or without CMR (CMR
      and sham CMR group), and the changes of endothelial function before and after CMR
      were compared. High-resolution ultrasound was used to measure flow-mediated
      endothelium-dilation (FMD) of the brachial artery. RESULTS: The FMD in CMR group
      at Day 1 after CMR was 3.60%, which was significantly lower than that (3.85%) in
      sham CMR group (p < 0.001). The levels of C-reactive protein (CRP),
      thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor alpha (TNF
      alpha) and interleukin-6(IL-6) in CMR group were significantly higher than those
      in sham CMR group at Day 1 (p < 0.001). But these characteristics did not differ
      between two groups at baseline, Day 2 and Day 3 (p > 0.05). Linear correlation
      and multiple regression analyses showed that CRP, TBARS, TNF-alpha and IL-6 were
      associated with FMD in the CMR group (p < 0.01). CONCLUSIONS: The present data
      showed that CMR scanning can reversibly suppress endothelial function, probably
      through the increased production of oxygen-derived free radicals and inflammatory
      reactions in Chinese men with type 2 diabetes, indicating that CMR should be used
      with caution in order to avoid unnecessary damage to the endothelium. CLINICAL
      TRIAL REGISTRATION URL: https://register.clinicaltrials.gov/, Unique Identifier:
      NCT02001753.

PMID- 25602856
TI  - Increased discordance between HeartScore and coronary artery calcification score
      after introduction of the new ESC prevention guidelines.
AB  - OBJECTIVES: The European HeartScore has traditionally differentiated between low
      and high-risk countries. Until 2012 Germany and Denmark were considered to be
      high-risk countries but have now been defined as low-risk countries. In this
      survey we aim to address the consequences of this downgrading. METHODS: A
      screening of 3932 randomly selected (mean age 56 years, 46% male) individuals
      from Germany and Denmark free of cardiovascular disease was performed.
      Traditional risk factors were determined, and the HeartScore was measured using
      both the low-risk and the high-risk country models. A non-contrast Cardiac-CT
      scan was performed to detect coronary artery calcification (CAC). RESULTS:
      Agreement of HeartScore risk groups with CAC groups was poor, but higher when
      applying the algorithm for the low-risk compared to the high-risk country model
      (agreement rate: 77% versus 63%, and weighted Kappa: 0.22 versus 0.15). However,
      the number of subjects with severe coronary calcification (CAC score >=400)
      increased in the low and intermediate HeartScore risk group from 78 to 147
      participants (from 2.7 % to 4.2 %, p = 0.001), when estimating the risk based on
      the algorithm for low-risk countries. CONCLUSION: As a consequence of the
      reclassification of Germany and Denmark as low-risk countries more people with
      severe atherosclerosis will be classified as having a low or intermediate risk of
      fatal cardiovascular disease.

PMID- 25602855
TI  - Low-density lipoprotein cholesterol was inversely associated with 3-year all
      cause mortality among Chinese oldest old: data from the Chinese Longitudinal
      Healthy Longevity Survey.
AB  - OBJECTIVE: Low-density lipoprotein cholesterol (LDL-C) is a risk factor for
      survival in middle-aged individuals, but conflicting evidence exists on the
      relationship between LDL-C and all-cause mortality among the elderly. The goal of
      this study was to assess the relationship between LDL-C and all-cause mortality
      among Chinese oldest old (aged 80 and older) in a prospective cohort study.
      METHODS: LDL-C concentration was measured at baseline and all-cause mortality was
      calculated over a 3-year period. Multiple statistical models were used to adjust
      for demographic and biological covariates. RESULTS: During three years of follow
      up, 447 of 935 participants died, and the overall all-cause mortality was 49.8%.
      Each 1 mmol/L increase of LDL-C concentration corresponded to a 19% decrease in 3
      year all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI]
      0.71-0.92). The crude HR for abnormally higher LDL-C concentration (>=3.37
      mmol/L) was 0.65 (0.41-1.03); and the adjusted HR was statistically significant
      around 0.60 (0.37-0.95) when adjusted for different sets of confounding factors.
      Results of sensitivity analysis also showed a significant association between
      higher LDL-C and lower mortality risk. CONCLUSIONS: Among the Chinese oldest old,
      higher LDL-C level was associated with lower risk of all-cause mortality. Our
      findings suggested the necessity of re-evaluating the optimal level of LDL-C
      among the oldest old.

PMID- 25602857
TI  - Effect of exercise-based cardiac rehabilitation on arterial stiffness and
      inflammatory and endothelial dysfunction biomarkers: a randomized controlled
      trial of myocardial infarction patients.
AB  - BACKGROUND: Arterial stiffness have shown an independent predictive value for
      cardiovascular and all-cause mortality. OBJECTIVE: This study sought to evaluate
      the effects of an 8-week exercise-based cardiac rehabilitation program (ECR) on
      arterial stiffness, and on inflammatory and endothelial dysfunction biomarkers.
      Additionally, it was assessed two potential confounding variables, daily physical
      activity and dietary intake. METHODS: In this parallel-group trial, 96 patients
      (56 +/- 10 years) were randomized to either the exercise group (EG) or control
      group (CG) 4 weeks after suffering acute myocardial infarction (MI). ECR
      consisted of 8 weeks of aerobic exercise at 70-85% of maximal heart rate during 3
      sessions weekly, plus usual care. CG participants received only usual care.
      Baseline and final assessments included arterial stiffness through carotid
      femoral pulse wave velocity (cf-PWV), inflammatory and endothelial dysfunction
      biomarkers, daily physical activity, and dietary intake. (ClinicalTrials.gov:
      NCT01432639). RESULTS: After 8 weeks, no significant changes were found between
      groups in cf-PWV, inflammatory and endothelial dysfunction biomarkers, daily
      physical activity, or dietary intake. Excluding those patients (n = 7) who did
      not attend, at least 80% of the exercise sessions provided similar results,
      excepting a significant reduction in cf-PWV in the EG compared to the CG.
      CONCLUSIONS: A short-term ECR does not seem to reduce arterial stiffness and
      inflammatory and endothelial dysfunction biomarkers of post-MI patients under
      optimized medication. Nevertheless, the decrease of cf-PWV observed in the EG,
      when considering only those patients who attended at least 80% of exercise
      sessions, warrants further investigation.

PMID- 25602858
TI  - Golimumab, the newest TNF-alpha blocker, comes of age.
AB  - Golimumab, a fully human monoclonal antibody against tumour necrosis factor-alpha
      (TNF-alpha) is one of the newest biologics that has become available for the
      treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic
      arthritis. Following the initial randomised double-blind placebo-controlled
      clinical trials, which demonstrated the efficacy and safety of the drug in the
      context of a limited patient sample and a relatively short time frame, golimumab
      has been the focus of continuous investigation through the extensions of the
      above-mentioned trials, new clinical trials and registries of biologic drug use
      in daily clinical practice. The review of this data and their inclusion in meta
      analyses and indirect comparisons across TNF-alpha blockers suggest that
      golimumab possesses similar properties regarding efficacy and safety as the older
      monoclonal anti-TNF-alpha antibodies. The novelty of golimumab is perhaps its
      dosing regimen, i.e. subcutaneous self-administration once monthly, which allows
      for the least disturbance in the life of patients. 

PMID- 25602860
TI  - Combining clinical and population-level data to understand the health of
      neighborhoods.
AB  - From February through December 2012, we examined responses to health behavior
      questions integrated into the electronic medical record of primary care centers
      in the Bronx, New York in the context of New York City Community Health Survey
      data. We saw a higher proportion of unhealthy behaviors among patients than among
      the neighborhood population. Analyzing clinical data in the neighborhood context
      can better target at-risk populations. 

PMID- 25602859
TI  - A window of opportunity: maximizing the effectiveness of new HCV regimens in the
      United States with the expansion of the Affordable Care Act.
AB  - Patients with chronic HCV have predictable overlapping comorbidities that reduce
      access to care. The Affordable Care Act (ACA) presents an opportunity to focus on
      the benefits of the medical home model for integrated chronic disease management.
      New, highly effective HCV treatment regimens in combination with the medical home
      model could reduce disease prevalence. We sought to address challenges posed by
      comorbidities in patients with chronic HCV infection and limitations within our
      health care system, and recommend solutions to maximize the public benefit from
      ACA and the new drug regimen. 

PMID- 25602862
TI  - Nonprofit hospitals' approach to community health needs assessment.
AB  - OBJECTIVES: We sought a better understanding of how nonprofit hospitals are
      fulfilling the community health needs assessment (CHNA) provision of the 2010
      Patient Protection and Affordable Care Act to conduct CHNAs and develop CHNA and
      implementation strategies reports. METHODS: Through an Internet search of an
      estimated 179 nonprofit hospitals in Texas conducted between December 1, 2013,
      and January 5, 2014, we identified and reviewed 95 CHNA and implementation
      strategies reports. We evaluated and scored reports with specific criteria. We
      analyzed hospital-related and other report characteristics to understand
      relationships with report quality. RESULTS: There was wide-ranging diversity in
      CHNA approaches and report quality. Consultant-led CHNA processes and
      collaboration with local health departments were associated with higher-quality
      reports. CONCLUSIONS: At the time of this study, the Internal Revenue Service had
      not yet issued the final regulations for the CHNA requirement. This provides an
      opportunity to strengthen the CHNA guidance for the final regulations, clarify
      the purpose of the assessment and planning process and reports, and better align
      assessment and planning activities through a public health framework.

PMID- 25602861
TI  - Impact of a letter-grade program on restaurant sanitary conditions and diner
      behavior in New York City.
AB  - OBJECTIVES: We evaluated the impact of the New York City restaurant letter
      grading program on restaurant hygiene, food safety practices, and public
      awareness. METHODS: We analyzed data from 43,448 restaurants inspected between
      2007 and 2013 to measure changes in inspection score and violation citations
      since program launch in July 2010. We used binomial regression to assess
      probability of scoring 0 to 13 points (A-range score). Two population-based
      random-digit-dial telephone surveys assessed public perceptions of the program.
      RESULTS: After we controlled for repeated restaurant observations, season of
      inspection, and chain restaurant status, the probability of scoring 0 to 13
      points on an unannounced inspection increased 35% (95% confidence interval
      [CI]=31%, 40%) 3 years after compared with 3 years before grading. There were
      notable improvements in compliance with some specific requirements, including
      having a certified kitchen manager on site and being pest-free. More than 91%
      (95% CI=88%, 94%) of New Yorkers approved of the program and 88% (95% CI=85%,
      92%) considered grades in dining decisions in 2012. CONCLUSIONS: Restaurant
      letter grading in New York City has resulted in improved sanitary conditions on
      unannounced inspection, suggesting that the program is an effective regulatory
      tool.

PMID- 25602863
TI  - A minimal intervention to promote smoke-free homes among 2-1-1 callers: a
      randomized controlled trial.
AB  - OBJECTIVES: We tested the efficacy of a minimal intervention to create smoke-free
      homes in low-income households recruited through the United Way of Greater
      Atlanta 2-1-1, an information and referral system that connects callers to local
      social services. METHODS: We conducted a randomized controlled trial (n=498) from
      June 2012 through June 2013, with follow-up at 3 and 6 months. The intervention
      consisted of 3 mailings and 1 coaching call. RESULTS: Participants were mostly
      smokers (79.7%), women (82.7%), African American (83.3%), and not employed
      (76.5%), with an annual household income of $10,000 or less (55.6%). At 6-months
      postbaseline, significantly more intervention participants reported a full ban on
      smoking in the home than did control participants (40.0% vs 25.4%; P=.002). The
      intervention worked for smokers and nonsmokers, as well as those with or without
      children. CONCLUSIONS: Minimal intervention was effective in promoting smoke-free
      homes in low income households and offers a potentially scalable model for
      protecting children and adult nonsmokers from secondhand smoke exposure in their
      homes.

PMID- 25602864
TI  - Opportunities for public health to increase physical activity among youths.
AB  - Despite the well-known benefits of youths engaging in 60 or more minutes of daily
      physical activity, physical inactivity remains a significant public health
      concern. The 2008 Physical Activity Guidelines for Americans (PAG) provides
      recommendations on the amount of physical activity needed for overall health; the
      PAG Midcourse Report (2013) describes effective strategies to help youths meet
      these recommendations. Public health professionals can be dynamic change agents
      where youths live, learn, and play by changing environments and policies to
      empower youths to develop regular physical activity habits to maintain throughout
      life. We have summarized key findings from the PAG Midcourse Report and outlined
      actions that public health professionals can take to ensure that all youths
      regularly engage in health-enhancing physical activity. 

PMID- 25602865
TI  - Allostatic load in foreign-born and US-born blacks: evidence from the 2001-2010
      National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: We tested whether the immigrant health advantage applies to non
      Hispanic Black immigrants and examined whether nativity-based differences in
      allostatic load exist among non-Hispanic Blacks. METHODS: We used pooled data
      from the 2001-2010 National Health and Nutrition Examination Survey to compare
      allostatic load scores for US-born (n = 2745) and foreign-born (n = 152) Black
      adults. We used multivariate logistic regression techniques to assess the
      association between nativity and high allostatic load scores, controlling for
      gender, age, health behaviors, and socioeconomic status. RESULTS: For foreign
      born Blacks, length of stay and age were powerful predictors of allostatic load
      scores. For older US-born Blacks and those who were widowed, divorced, or
      separated, the risk of high allostatic load was greater. CONCLUSIONS: Foreign
      born Blacks have a health advantage in allostatic load. Further research is
      needed that underscores a deeper understanding of the mechanisms driving this
      health differential to create programs that target these populations differently.

PMID- 25602866
TI  - Toward improved public health outcomes from urban nature.
AB  - There is mounting concern for the health of urban populations as cities expand at
      an unprecedented rate. Urban green spaces provide settings for a remarkable range
      of physical and mental health benefits, and pioneering health policy is
      recognizing nature as a cost-effective tool for planning healthy cities. Despite
      this, limited information on how specific elements of nature deliver health
      outcomes restricts its use for enhancing population health. We articulate a
      framework for identifying direct and indirect causal pathways through which
      nature delivers health benefits, and highlight current evidence. We see a need
      for a bold new research agenda founded on testing causality that transcends
      disciplinary boundaries between ecology and health. This will lead to cost
      effective and tailored solutions that could enhance population health and reduce
      health inequalities. 

PMID- 25602867
TI  - Ethical Challenges in School-Based Immunization Programs for Adolescents: A
      Qualitative Study.
AB  - OBJECTIVES: We investigated ethical issues in school-based immunization programs
      for adolescents and how they are addressed. METHODS: We used qualitative methods
      and an ethnographic approach to observe 9 secondary schools on immunization days
      in South Australia in 2011; concurrently, we conducted 9 focus groups with female
      secondary school students, 6 semistructured interviews with parents, and 10
      interviews with nurses and teachers. We explored ethical challenges from the
      perspective of these groups. RESULTS: We identified ethical challenges for the
      delivery of adolescent immunization in a school-based setting in 3 main areas:
      informed consent, restrictions on privacy, and harm to students in the form of
      fear and anxiety. CONCLUSIONS: We found areas in which the design and delivery of
      school-based immunization programs can be improved. Information about
      immunization should be provided in ways that are appropriate to young people and
      their parents, and privacy protections should be enhanced when possible.
      Involving young people in the design and delivery of programs would assist with
      making these improvements.

PMID- 25602868
TI  - Changes in awareness and use of calorie information after mandatory menu labeling
      in restaurants in King County, Washington.
AB  - OBJECTIVES: We examined population-level impact on customer awareness and use and
      explored potential disparities in outcomes regarding the King County, Washington,
      regulation requiring chain restaurants to provide calorie information. METHODS:
      We analyzed 2008 to 2010 Behavioral Risk Factor Surveillance System data from
      3132 English-speaking King County residents aged 18 years and older who reported
      eating at a regulated chain. We used regression models to assess changes in
      calorie information awareness and use from prepolicy to postpolicy implementation
      by customer demographics, health status, and restaurant type. RESULTS: Calorie
      information awareness and use increased significantly from 2008 to 2010.
      Unadjusted analyses indicated that the proportion who saw and used calorie
      information tripled, from 8.1% to 24.8%. Fully adjusted analyses confirmed
      significant increases. After policy implementation, White, higher income, and
      obese respondents had greater odds of seeing calorie information. Women, higher
      income groups, and those eating at a fast-food versus a sit-down chain restaurant
      were more likely to use this information. CONCLUSIONS: Significant increases in
      calorie information awareness and use following regulation support the population
      wide value of this policy. However, improvements varied across race, income, and
      gender.

PMID- 25602870
TI  - Identifying a sample of HIV-positive beneficiaries from Medicaid claims data and
      estimating their treatment costs.
AB  - OBJECTIVES: We sought to identify people living with HIV/AIDS from Medicare and
      Medicaid claims data to estimate Medicaid costs for treating HIV/AIDS in
      California. We also examined how alternate methods of identifying the relevant
      sample affect estimates of per capita costs. METHODS: We analyzed data on
      Californians enrolled in Medicaid with an HIV/AIDS diagnosis reported in 2007
      Medicare or Medicaid claims data. We compared alternative selection criteria by
      examining use of antiretroviral drugs, HIV-specific monitoring tests, and medical
      costs. We compared the final sample and average costs with other estimates of the
      size of California's HIV/AIDS population covered by Medicaid in 2007 and their
      average treatment costs. RESULTS: Eighty-seven percent (18,290) of potentially
      identifiable HIV-positive individuals satisfied at least 1 confirmation
      criterion. Nearly 80% of confirmed observations had claims for HIV-specific
      tests, compared with only 3% of excluded cases. Female Medicaid recipients were
      particularly likely to be miscoded as having HIV. Medicaid treatment spending for
      Californians with HIV averaged $33,720 in 2007. CONCLUSIONS: The proposed
      algorithm displays good internal and external validity. Accurately identifying
      HIV cases in claims data is important to avoid drawing biased conclusions and is
      necessary in setting appropriate HIV managed-care capitation rates.

PMID- 25602869
TI  - Nativity and neighborhood characteristics and cervical cancer stage at diagnosis
      and survival outcomes among Hispanic women in California.
AB  - OBJECTIVES: We examined stage of diagnosis and survival after cervical cancer
      among Hispanic women, and their associations with Hispanic nativity, and explored
      whether neighborhood socioeconomic status (SES) and residence in a Hispanic
      enclave modify the association of nativity with stage and survival. METHODS: We
      used California Cancer Registry data (1994-2009) to identify 7958 Hispanic women
      aged 21 years and older with invasive cervical cancer. We used logistic and Cox
      proportional hazards models to estimate the associations between stage and
      mortality with nativity, neighborhood factors, and other covariates. RESULTS:
      Foreign-born women had similar adjusted relative odds of being diagnosed with
      stages II through IV (vs stage I) cervical cancer compared with US-born Hispanic
      women. However, among foreign-born women, those in low-SES-low-enclave
      neighborhoods were more likely to have late-stage disease than those in high-SES
      low-enclave neighborhoods (adjusted odds ratio=1.91; 95% confidence
      interval=1.18, 3.07). Foreign-born women had lower cervical cancer mortality
      (adjusted hazard ratio=0.67; 95% confidence interval=0.58, 0.76) than US-born
      women, but only in high enclaves. CONCLUSIONS: Among Hispanic women, nativity,
      neighborhood enclaves, and SES interact in their influence on stage and survival
      of cervical cancer.

PMID- 25602871
TI  - Agent-based modeling of noncommunicable diseases: a systematic review.
AB  - We reviewed the use of agent-based modeling (ABM), a systems science method, in
      understanding noncommunicable diseases (NCDs) and their public health risk
      factors. We systematically reviewed studies in PubMed, ScienceDirect, and Web of
      Sciences published from January 2003 to July 2014. We retrieved 22 relevant
      articles; each had an observational or interventional design. Physical activity
      and diet were the most-studied outcomes. Often, single agent types were modeled,
      and the environment was usually irrelevant to the studied outcome. Predictive
      validation and sensitivity analyses were most used to validate models. Although
      increasingly used to study NCDs, ABM remains underutilized and, where used, is
      suboptimally reported in public health studies. Its use in studying NCDs will
      benefit from clarified best practices and improved rigor to establish its
      usefulness and facilitate replication, interpretation, and application. 

PMID- 25602872
TI  - Postarrival Tuberculosis Screening of High-Risk Immigrants at a Local Health
      Department.
AB  - OBJECTIVES: We sought to characterize postimmigration tuberculosis (TB) care for
      Class B immigrants and refugees at the Baltimore City Health Department TB
      program (BCHD), and to determine the proportion of immigrants with active TB or
      latent TB infection (LTBI) in this high-risk population. METHODS: We conducted a
      retrospective chart review of Class B immigrants and refugees who reported to the
      BCHD for postimmigration TB evaluation from 2010 to 2012. RESULTS: We reviewed
      the clinical records of 153 Class B immigrants; 4% were diagnosed with active TB
      and 53% were diagnosed with LTBI. Fifty percent of active TB cases were culture
      positive, and 67% were asymptomatic; 100% received and completed active TB
      therapy at the BCHD. Among those diagnosed with LTBI, 87% initiated LTBI therapy
      and 91% completed treatment. CONCLUSIONS: The high prevalence of active TB and
      LTBI found among Class B immigrants underscore the importance for postarrival TB
      screening. The absence of reported symptoms among the majority of active cases
      identified during this study suggest that reliance on symptom-based screening
      protocols to prompt sputa testing may be inadequate for identifying active TB
      among this high-risk group.

PMID- 25602873
TI  - Self-help for weight loss in overweight and obese adults: systematic review and
      meta-analysis.
AB  - We conducted a systematic review and meta-analysis investigating the components
      and effectiveness of self-help weight-loss interventions and their applicability
      to less-advantaged populations. We searched (November 2013) for randomized
      controlled trials comparing self-help interventions with each other or with
      minimal controls in overweight and obese adults, with 6 months or longer follow
      up. We calculated mean difference between intervention and control for 6- and 12
      month weight change. Twenty-three studies met the inclusion criteria (9632
      participants; 39 intervention arms). Intervention participants lost significantly
      more weight than controls at 6 months (mean difference -1.85 kg; 95% confidence
      interval [CI]=-2.86, -0.83; 7 studies). No significant effect was detected at 12
      months but results were sensitive to the inclusion of 1 study at high risk of
      bias. Interactive programs appeared more effective than standard ones at 6 months
      (mean difference -0.94 kg; 95% CI=-1.50, -0.38). Evidence is insufficient to
      reach conclusions on effectiveness in socioeconomically disadvantaged people, but
      suggests self-help interventions may be less effective in this group.

PMID- 25602874
TI  - Higher price, fewer packs: evaluating a tobacco tax increase with cigarette sales
      data.
AB  - In 2013, Minnesota increased cigarette taxes by $1.75, the largest US state
      increase since 2000. We obtained convenience store data of cigarette sales from
      January 2012 to December 2013 from the Nielsen Company. Analysis revealed
      significantly greater year-to-year reductions in numbers of packs purchased
      during posttax (-12.1%) than pretax (-3.2%; P<.001) periods. The results provide
      contemporary evidence that, despite reduced prevalence and increased tobacco
      control efforts, tax increases remain an effective tobacco control strategy.

PMID- 25602875
TI  - Fast-food fights: news coverage of local efforts to improve food environments
      through land-use regulations, 2001-2013. [corrected].
AB  - Zoning and other land-use policies are a promising but controversial strategy to
      improve community food environments. To understand how these policies are
      debated, we searched existing databases and the Internet and analyzed news
      coverage and legal documentation of efforts to restrict fast-food restaurants in
      77 US communities in 2001 to 2013. Policies intended to improve community health
      were most often proposed in urban, racially diverse communities; policies
      proposed in small towns or majority-White communities aimed to protect community
      aesthetics or local businesses. Health-focused policies were subject to more
      criticism than other policies and were generally less successful. Our findings
      could inform the work of advocates interested in employing land-use policies to
      improve the food environment in their own communities. 

PMID- 25602876
TI  - Pictorial cigarette pack warnings have important effects.

PMID- 25602877
TI  - Assessing the effects of a complementary parent intervention and prior exposure
      to a preadolescent program of HIV risk reduction for mid-adolescents.
AB  - OBJECTIVES: We (1) evaluated the impact of an evidence-based HIV prevention
      program with and without a parent component among mid-adolescents living in the
      Caribbean and (2) determined the effect of prior receipt of a related
      intervention during preadolescence on intervention response. METHODS: A
      randomized, controlled 4-cell trial of a 10-session, theory-based HIV prevention
      intervention involving 2564 Bahamian grade-10 youths (some of whom had received a
      comparable intervention in grade 6) was conducted (2008-2011). Randomization
      occurred at the level of the classroom with follow-up at 6, 12, and 18 months
      after intervention. The 3 experimental conditions all included the youths'
      curriculum and either a youth-parent intervention emphasizing adolescent-parent
      communication, a parent-only goal-setting intervention, or no parent
      intervention. RESULTS: An intervention delivered to mid-adolescents in
      combination with a parent-adolescent sexual-risk communication intervention
      increased HIV/AIDS knowledge, condom-use skills, and self-efficacy and had a
      marginal effect on consistent condom use. Regardless of prior exposure to a
      similar intervention as preadolescents, youths benefited from receipt of the
      intervention. CONCLUSIONS: Preadolescents and mid-adolescents in HIV-affected
      countries should receive HIV prevention interventions that include parental
      participation.

PMID- 25602878
TI  - Relation between annual trends in food pantry use and long-term unemployment in
      New York State, 2002-2012.
AB  - We examined the correlation between trends in meals provided through food
      pantries and long-term unemployment from 2002 through 2012. The New York State
      Hunger Prevention and Nutrition Assistance Program provided about 192 million
      meals through food pantries in 2012-double the number before the Great Recession.
      Annual food pantry use was strongly correlated with long-term unemployment and
      remained on an upward trend from 2006 through 2012, even after the Great
      Recession had ended. These findings suggest that efforts to reduce hunger and
      food insecurity should continue to be priorities. 

PMID- 25602879
TI  - Too little, too late: ineffective regulation of dietary supplements in the United
      States.
AB  - Millions of people in the United States consume dietary supplements hoping to
      maintain or improve their health; however, extensive research has failed to
      demonstrate the efficacy of numerous supplements in disease prevention. In
      addition, concerns about the safety of routine and high-dose supplementation have
      been raised. The Food and Drug Administration regulates dietary supplement
      quality, safety, and labeling, and the Federal Trade Commission monitors
      advertisements and marketing; still, vast enforcement challenges remain, and
      optimal governmental oversight has not been achieved. If the composition and
      quality of ingredients cannot be reliably ensured, the validity of research on
      dietary supplements is questionable. Moreover, the health of the US public is put
      at risk. 

PMID- 25602880
TI  - A comprehensive approach to address the prescription opioid epidemic in
      Washington State: milestones and lessons learned.
AB  - An epidemic of morbidity and mortality has swept across the United States related
      to the use of prescription opioids for chronic noncancer pain. More than 100,000
      people have died from unintentional overdose, making this one of the worst
      manmade epidemics in history. Much of health care delivery in the United States
      is regulated at the state level; therefore, both the cause and much of the cure
      for the opioid epidemic will come from state action. We detail the strong
      collaborations across executive health care agencies, and between those public
      agencies and practicing leaders in the pain field that have led to a substantial
      reversal of the epidemic in Washington State.

PMID- 25602881
TI  - Acceptable interventions to reduce syphilis transmission among high-risk men who
      have sex with men in Los Angeles.
AB  - OBJECTIVES: We examined perceptions of and attitudes toward existing and
      potential syphilis interventions, including case management and Web-based
      programs, to increase syphilis testing among high-risk men who have sex with men
      (MSM). METHODS: Between October 2010 and June 2011, we conducted in-depth
      interviews with 19 MSM in Los Angeles, California, with repeat early syphilis
      infections (primary, secondary, and early latent syphilis) within the previous 5
      years. We analyzed the interviews inductively to determine the most acceptable
      potential interventions. RESULTS: Experiences with health department and
      community-based standard of care case management were generally positive. The
      most popular interventions among respondents included a Web site providing
      information on syphilis and syphilis testing, automated Web reminders to test,
      being paid to test, free online home testing kits, and preexposure prophylactic
      medication. Respondents' beliefs that they would continue to practice high-risk
      sexual behaviors reinforced their reasons for wanting increased accessibility and
      convenient testing strategies. CONCLUSIONS: Public health officials should
      consider participant responses to potential interventions for syphilis, which
      suggest that high-risk MSM would consider testing more often or using other
      interventions.

PMID- 25602882
TI  - Migrants in transit: the importance of monitoring HIV risk among migrant flows at
      the Mexico-US border.
AB  - We conducted a probability-based survey of migrant flows traveling across the
      Mexico-US border, and we estimated HIV infection rates, risk behaviors, and
      contextual factors for migrants representing 5 distinct migration phases. Our
      results suggest that the influence of migration is not uniform across genders or
      risk factors. By considering the predeparture, transit, and interception phases
      of the migration process, our findings complement previous studies on HIV among
      Mexican migrants conducted at the destination and return phases. Monitoring HIV
      risk among this vulnerable transnational population is critical for better
      understanding patterns of risk at different points of the migration process and
      for informing the development of protection policies and programs. 

PMID- 25602883
TI  - Accelerometer-monitored sedentary behavior and observed physical function loss.
AB  - OBJECTIVES: We examined whether objectively measured sedentary behavior is
      related to subsequent functional loss among community-dwelling adults with or at
      high risk for knee osteoarthritis. METHODS: We analyzed longitudinal data (2008
      2012) from 1659 Osteoarthritis Initiative participants aged 49 to 83 years in 4
      cities. Baseline sedentary time was assessed by accelerometer monitoring.
      Functional loss (gait speed and chair stand testing) was regressed on baseline
      sedentary time and covariates (baseline function; socioeconomics [age, gender,
      race/ethnicity, income, education], health factors [obesity, depression,
      comorbidities, knee symptoms, knee osteoarthritis severity, prior knee injury,
      other lower extremity pain, smoking], and moderate-to-vigorous activity).
      RESULTS: This cohort spent almost two thirds of their waking hours (average=9.8
      h) in sedentary behaviors. Sedentary time was significantly positively associated
      with subsequent functional loss in both gait speed (-1.66 ft/min decrease per 10%
      increment sedentary percentage waking hours) and chair stand rate (-0.75
      repetitions/min decrease), controlling for covariates. CONCLUSIONS: Being less
      sedentary was related to less future decline in function, independent of time
      spent in moderate-to-vigorous activity. Both limiting sedentary activities and
      promoting physical activity in adults with knee osteoarthritis may be important
      in maintaining function.

PMID- 25602884
TI  - Psychotropic drug use among preschool children in the Medicaid program from 36
      states.
AB  - OBJECTIVES: We determined the prevalence of and indications for psychotropic
      medication among preschool children in Medicaid. METHODS: We obtained 2000 to
      2003 Medicaid Analytic Extract data from 36 states. We followed children in 2
      cohorts, born in 1999 and 2000, up to age 4 years. We used logistic regression to
      model odds of receiving medications for (1) attention-deficit disorder/attention
      deficit hyperactivity disorder, (2) depression or anxiety, and (3) psychotic
      illness or bipolar. RESULTS: Overall, 1.19% of children received at least 1
      psychotropic drug. Medications for attention-deficit disorder/attention-deficit
      hyperactivity disorder treatment were most common (0.61% of all children),
      followed by depression or anxiety (0.59%) and psychotic illness or bipolar
      (0.24%). Among children, boys, those of other or unknown race compared with
      White, and those with other insurance compared with fee for service-only had
      higher odds of receiving a prescription (odds ratio [OR]=1.80 [95% confidence
      interval (CI)=1.74, 1.86], 1.75 [corrected] [1.66, 1.85], and 1.14 [1.01, 1.28],
      respectively), whereas Black and Hispanic children had lower odds (OR=0.51 [95%
      CI=0.48, 0.53] and 0.37 [0.34, 0.39], respectively). CONCLUSIONS: Preschoolers
      are receiving psychotropic medications despite limited evidence supporting safety
      or efficacy. Future research should focus on implementing medication use practice
      parameters in infant and toddler clinics, and expanding psychosocial
      interventions for young children with behavioral problems.

PMID- 25602885
TI  - Prospective association between negative life events and initiation of sexual
      intercourse: the influence of family structure and family income.
AB  - OBJECTIVES: We examined the prospective association between negative life events
      and time to initiation of sexual intercourse and the influence of family
      structure and family income on this association. METHODS: We followed up a
      randomly selected sample (n=649) of ethnically diverse parents and their children
      aged 12 to 17 years over a 5-year period. We conducted Cox proportional hazards
      regression analysis to examine the relation between negative life events and time
      to initiation of sexual intercourse. Family structure and family income were
      assessed as confounders. RESULTS: Negative life events were significant
      predictors of time to initiation of sexual intercourse in adolescents. After
      controlling for demographic variables, youths reporting 1 negative life event had
      a hazard of initiation of sexual intercourse 1.40 times greater and youths
      reporting 2 or more negative life events had a hazard of initiation of sexual
      intercourse 1.61 times greater compared with youths reporting no negative life
      events. Family structure and family income were not significant confounders of
      the relation between initiation of sexual intercourse and negative life events.
      CONCLUSIONS: Interventions to prevent initiation of sexual intercourse should
      focus on youths with recent negative life events, regardless of family income and
      structure.

PMID- 25602887
TI  - The impact of green stormwater infrastructure installation on surrounding health
      and safety.
AB  - OBJECTIVES: We investigated the health and safety effects of urban green
      stormwater infrastructure (GSI) installments. METHODS: We conducted a difference
      in-differences analysis of the effects of GSI installments on health (e.g., blood
      pressure, cholesterol and stress levels) and safety (e.g., felonies, nuisance and
      property crimes, narcotics crimes) outcomes from 2000 to 2012 in Philadelphia,
      Pennsylvania. We used mixed-effects regression models to compare differences in
      pre- and posttreatment measures of outcomes for treatment sites (n=52) and
      randomly chosen, matched control sites (n=186) within multiple geographic extents
      surrounding GSI sites. RESULTS: Regression-adjusted models showed consistent and
      statistically significant reductions in narcotics possession (18%-27% less)
      within 16th-mile, quarter-mile, half-mile (P<.001), and eighth-mile (P<.01)
      distances from treatment sites and at the census tract level (P<.01). Narcotics
      manufacture and burglaries were also significantly reduced at multiple scales.
      Nonsignificant reductions in homicides, assaults, thefts, public drunkenness, and
      narcotics sales were associated with GSI installation in at least 1 geographic
      extent. CONCLUSIONS: Health and safety considerations should be included in
      future assessments of GSI programs. Subsequent studies should assess mechanisms
      of this association.

PMID- 25602886
TI  - State and municipal innovations in obesity policy: why localities remain a
      necessary laboratory for innovation.
AB  - Municipal and state governments are surging ahead in obesity prevention,
      providing a testing ground for innovative policies and shifting social norms in
      the process. Though high-profile measures such as New York City's soda portion
      rule attract significant media attention, we catalog the broader array of
      initiatives in less-known localities. Local innovation advances prevention
      policy, but faces legal and political constraints-constitutional challenges,
      preemption, charges of paternalism, lack of evidence, and widening health
      inequalities. These arguments can be met with astute framing, empirical evidence,
      and policy design, enabling local governments to remain at the forefront in
      transforming obesogenic environments. 

PMID- 25602888
TI  - Weighing in: the taste-engineering frame in obesity expert discourse.
AB  - OBJECTIVES: We sought expert opinion on the problems with 2 dominant obesity
      prevention discourse frames-personal responsibility and the environment-and
      examined alternative frames for understanding and addressing obesity. METHODS: We
      conducted 60-minute, semistructured interviews with 15 US-based obesity experts.
      We manually coded and entered interview transcripts into software, generating
      themes and subthematic areas that captured the debate's essence. RESULTS:
      Although the environmental frame is the dominant model used in communications
      with the public and policymakers, several experts found that communicating key
      messages within this frame was difficult because of the enormity of the obesity
      problem. A subframe of the environmental frame--the taste-engineering frame-
      identifies food industry strategies to influence the overconsumption of certain
      foods and beverages. This emerging frame deconstructs the environmental frame so
      that causal attributes and responsible agents are more easily identifiable and
      proposed policies and public health interventions more salient. CONCLUSIONS:
      Expert interviews are an invaluable resource for understanding how experts use
      frames in discussing their work and in conversations with the public and
      policymakers. Future empirical studies testing the effectiveness of the taste
      engineering frame on public opinion and support for structural-level health
      policies are needed.

PMID- 25602889
TI  - Efficacy of a savings-led microfinance intervention to reduce sexual risk for HIV
      among women engaged in sex work: a randomized clinical trial.
AB  - OBJECTIVES: We tested whether a structural intervention combining savings-led
      microfinance and HIV prevention components would achieve enhanced reductions in
      sexual risk among women engaging in street-based sex work in Ulaanbaatar,
      Mongolia, compared with an HIV prevention intervention alone. METHODS: Between
      November 2011 and August 2012, we randomized 107 eligible women who completed
      baseline assessments to either a 4-session HIV sexual risk reduction intervention
      (HIVSRR) alone (n=50) or a 34-session HIVSRR plus a savings-led microfinance
      intervention (n=57). At 3- and 6-month follow-up assessments, participants
      reported unprotected acts of vaginal intercourse with paying partners and number
      of paying partners with whom they engaged in sexual intercourse in the previous
      90 days. Using Poisson and zero-inflated Poisson model regressions, we examined
      the effects of assignment to treatment versus control condition on outcomes.
      RESULTS: At 6-month follow-up, the HIVSRR plus microfinance participants reported
      significantly fewer paying sexual partners and were more likely to report zero
      unprotected vaginal sex acts with paying sexual partners. CONCLUSIONS: Findings
      advance the HIV prevention repertoire for women, demonstrating that risk
      reduction may be achieved through a structural intervention that relies on asset
      building, including savings, and alternatives to income from sex work.

PMID- 25602891
TI  - Translating a Fall Prevention Intervention Into Practice: A Randomized Community
      Trial.
AB  - OBJECTIVES: We examined whether community translation of an effective evidence
      based fall prevention program via standard monetary support can produce a
      community-wide reduction in fall injuries in older adults and evaluated whether
      an enhanced version with added technical support and capacity building amplified
      the fall reduction effect. METHODS: We completed a randomized controlled
      community trial among adults aged 65 and older in (1) 10 control communities
      receiving no special resources or guidance on fall prevention, (2) 5 standard
      support communities receiving modest funding to implement Stepping On, and (3) 5
      enhanced support communities receiving funding and technical support. The primary
      outcome was hospital inpatient and emergency department discharges for falls,
      examined with Poisson regression. RESULTS: Compared with control communities,
      standard and enhanced support communities showed significantly higher community
      wide reductions (9% and 8%, respectively) in fall injuries from baseline (2007
      2008) to follow-up (2010-2011). No significant difference was found between
      enhanced and standard support communities. CONCLUSIONS: Population-based fall
      prevention interventions can be effective when implemented in community settings.
      More research is needed to identify the barriers and facilitators that influence
      the successful adoption and implementation of fall prevention interventions into
      broad community practice.

PMID- 25602890
TI  - Household crowding and food insecurity among Inuit families with school-aged
      children in the Canadian Arctic.
AB  - OBJECTIVES: We examined the relation of household crowding to food insecurity
      among Inuit families with school-aged children in Arctic Quebec. METHODS: We
      analyzed data collected between October 2005 and February 2010 from 292 primary
      caregiver-child dyads from 14 Inuit communities. We collected information about
      household conditions, food security, and family socioeconomic characteristics by
      interviews. We used logistic regression models to examine the association between
      household crowding and food insecurity. RESULTS: Nearly 62% of Inuit families in
      the Canadian Arctic resided in more crowded households, placing them at risk for
      food insecurity. About 27% of the families reported reducing the size of their
      children's meals because of lack of money. The likelihood of reducing the size of
      children's meals was greater in crowded households (odds ratio=3.73; 95%
      confidence interval=1.96, 7.12). After we adjusted for different socioeconomic
      characteristics, results remained statistically significant. CONCLUSIONS:
      Interventions operating across different levels (community, regional, national)
      are needed to ensure food security in the region. Targeting families living in
      crowded conditions as part of social and public health policies aiming to reduce
      food insecurity in the Arctic could be beneficial.

PMID- 25602892
TI  - Racial/Ethnic Disparities in the Self-Reported Number of Drinks in 2 Hours Before
      Driving Becomes Impaired.
AB  - OBJECTIVES: We used data on self-reported impaired driving and the number of
      drinks the person states he or she can have in 2 hours before impairment to
      evaluate predictors of individuals' impairment thresholds by race/ethnicity.
      METHODS: Data come from the 2000, 2005, and 2010 US National Alcohol Surveys,
      with oversamples of Black and Hispanic populations. We estimated negative
      binomial models overall, by gender, and for those who reported impaired driving.
      Analyses focused primarily on 8553 respondents who drank alcohol and drove a car
      in the past year. RESULTS: In models that controlled for relevant available
      measures including body weight, sociodemographics, and drinking patterns, we
      found perceived impairment thresholds to be 30.3% (95% confidence interval = 23%,
      38%) higher for Black drinkers and 26.3% (95% confidence interval = 18%, 35%)
      higher for Hispanic drinkers compared with White drinkers. CONCLUSIONS: The
      greater number of standard drinks before perceived impairment reported by Black
      and Hispanic drivers implies a likely relative underreport of impaired driving
      and potentially higher severity of impairment when driving relative to White
      drivers.

PMID- 25602893
TI  - When advocacy obscures accuracy online: digital pandemics of public health
      misinformation through an antifluoride case study.
AB  - OBJECTIVES: In an antifluoridation case study, we explored digital pandemics and
      the social spread of scientifically inaccurate health information across the Web,
      and we considered the potential health effects. METHODS: Using the social
      networking site Facebook and the open source applications Netvizz and Gephi, we
      analyzed the connectedness of antifluoride networks as a measure of social
      influence, the social diffusion of information based on conversations about a
      sample scientific publication as a measure of spread, and the engagement and
      sentiment about the publication as a measure of attitudes and behaviors. RESULTS:
      Our study sample was significantly more connected than was the social networking
      site overall (P<.001). Social diffusion was evident; users were forced to
      navigate multiple pages or never reached the sample publication being discussed
      60% and 12% of the time, respectively. Users had a 1 in 2 chance of encountering
      negative and nonempirical content about fluoride unrelated to the sample
      publication. CONCLUSIONS: Network sociology may be as influential as the
      information content and scientific validity of a particular health topic
      discussed using social media. Public health must employ social strategies for
      improved communication management.

PMID- 25602894
TI  - The case for the World Health Organization's Commission on Social Determinants of
      Health to address gender identity.
AB  - We analyzed the case of the World Health Organization's Commission on Social
      Determinants of Health, which did not address gender identity in their final
      report. We argue that gender identity is increasingly being recognized as an
      important social determinant of health (SDH) that results in health inequities.
      We identify right to health mechanisms, such as established human rights
      instruments, as suitable policy tools for addressing gender identity as an SDH to
      improve health equity. We urge the World Health Organization to add gender
      identity as an SDH in its conceptual framework for action on the SDHs and to
      develop and implement specific recommendations for addressing gender identity as
      an SDH. 

PMID- 25602895
TI  - "Hidden" social networks in behavior change interventions.
AB  - We investigated whether "hidden" (or unobserved) social networks were evident in
      a 2011 physical activity behavior change intervention in Belfast, Northern
      Ireland. Results showed evidence of unobserved social networks in the
      intervention and illustrated how the network evolved over short periods and
      affected behavior. Behavior change interventions should account for the
      interaction among participants (i.e., social networks) and how such interactions
      affect intervention outcome. 

PMID- 25602896
TI  - Creating incentives to move upstream: developing a diversified portfolio of
      population health measures within payment and health care reform.
AB  - I examined the feasibility of developing a balanced portfolio of population
      health measures that would be useful within the current deliberations about
      health care and payment reform. My commentary acknowledges that an obstacle to
      the selection of population health metrics is the differing definitions of
      population health. Rather than choosing between these definitions, I identified
      five categories of indicators, ranging from traditional clinical care prevention
      interventions to those that measure investment in community-level nonclinical
      services, that in various combinations might yield the most promising results. I
      offer concrete examples of markers in each of the categories and show that there
      is a growing number of individuals eager to receive concrete recommendations and
      implement population health pilot programs. 

PMID- 25602897
TI  - Impact of regulatory interventions to reduce intake of artificial trans-fatty
      acids: a systematic review.
AB  - We examined the impact of regulatory action to reduce levels of artificial trans
      fatty acids (TFAs) in food. We searched Medline, Embase, ISI Web of Knowledge,
      and EconLit (January 1980 to December 2012) for studies related to government
      regulation of food- or diet-related health behaviors from which we extracted the
      subsample of legislative initiatives to reduce artificial TFAs in food. We
      screened 38 162 articles and identified 14 studies that examined artificial TFA
      controls limiting permitted levels or mandating labeling. These measures achieved
      good compliance, with evidence of appropriate reformulation. Regulations grounded
      on maximum limits and mandated labeling can lead to reductions in actual and
      reported TFAs in food and appear to encourage food producers to reformulate their
      products. 

PMID- 25602898
TI  - Redesigning primary care to tackle the global epidemic of noncommunicable
      disease.
AB  - Noncommunicable diseases (NCDs) have become the major contributors to death and
      disability worldwide. Nearly 80% of the deaths in 2010 occurred in low- and
      middle-income countries, which have experienced rapid population aging,
      urbanization, rise in smoking, and changes in diet and activity. Yet the health
      systems of low- and middle-income countries, historically oriented to infectious
      disease and often severely underfunded, are poorly prepared for the challenge of
      caring for people with cardiovascular disease, diabetes, cancer, and chronic
      respiratory disease. We have discussed how primary care can be redesigned to
      tackle the challenge of NCDs in resource-constrained countries. We suggest that
      four changes will be required: integration of services, innovative service
      delivery, a focus on patients and communities, and adoption of new technologies
      for communication. 

PMID- 25602899
TI  - HIV Prevalence and Awareness of Positive Serostatus Among Men Who Have Sex With
      Men and Transgender Women in Bogota, Colombia.
AB  - OBJECTIVES: We estimated HIV prevalence among men who have sex with men (MSM) and
      transgender women in Bogota, Colombia, and explored differences between HIV
      positive individuals who are aware and unaware of their serostatus. METHODS: In
      this cross-sectional 2011 study, we used respondent-driven sampling (RDS) to
      recruit 1000 MSM and transgender women, who completed a computerized
      questionnaire and received an HIV test. RESULTS: The RDS-adjusted prevalence was
      12.1% (95% confidence interval [CI] = 8.7, 15.8), comparable to a previous RDS
      derived estimate. Among HIV-positive participants, 39.7% (95% CI = 25.0, 54.8)
      were aware of their serostatus and 60.3% (95% CI = 45.2, 75.5) were unaware
      before this study. HIV-positive-unaware individuals were more likely to report
      inadequate insurance coverage, exchange sex (i.e., sexual intercourse in exchange
      for money, goods, or services), and substance use than other participants. HIV
      positive-aware participants were least likely to have had condomless anal
      intercourse in the previous 3 months. Regardless of awareness, HIV-positive
      participants reported more violence and forced relocation experiences than HIV
      negative participants. CONCLUSIONS: There is an urgent need to increase HIV
      detection among MSM and transgender women in Bogota. HIV-positive-unaware group
      characteristics suggest an important role for structural, social, and individual
      interventions.

PMID- 25602900
TI  - Putting the mouth back in the head: HEENT to HEENOT.
AB  - Improving oral health is a leading population health goal; however, curricula
      preparing health professionals have a dearth of oral health content and clinical
      experiences. We detail an educational and clinical innovation transitioning the
      traditional head, ears, eyes, nose, and throat (HEENT) examination to the
      addition of the teeth, gums, mucosa, tongue, and palate examination (HEENOT) for
      assessment, diagnosis, and treatment of oral-systemic health. Many New York
      University nursing, dental, and medical faculty and students have been exposed to
      interprofessional oral health HEENOT classroom, simulation, and clinical
      experiences. This was associated with increased dental-primary care referrals.
      This innovation has potential to build interprofessional oral health workforce
      capacity that addresses a significant public health issue, increases oral health
      care access, and improves oral-systemic health across the lifespan. 

PMID- 25602901
TI  - Program fidelity measures associated with an effective child restraint program:
      Buckle-Up Safely.
AB  - OBJECTIVES: We sought to identify the program fidelity factors associated with
      successful implementation of the Buckle-Up Safely program, targeting correct use
      of age-appropriate child car restraints. METHODS: In 2010, we conducted a cluster
      randomized controlled trial of 830 families with children attending preschools
      and long day care centers in South West Sydney, New South Wales, Australia.
      Families received the Buckle-Up Safely program in the intervention arm of the
      study (13 services). Independent observers assessed the type of restraint and
      whether it was used correctly. RESULTS: This detailed process evaluation showed
      that the multifaceted program was implemented with high fidelity. Program
      protocols were adhered to and messaging was consistently delivered. Results from
      multilevel and logistic regression analyses show that age-appropriate restraint
      use was associated with attendance at a parent information session hosted at the
      center (adjusted odd ratio [AOR]=3.66; 95% confidence interval [CI]=1.61, 8.29)
      and adversely affected by the child being aged 2 to 3 years (AOR=0.14; 95%
      CI=0.07, 0.30) or being from a family with more than 2 children (AOR=0.34; 95%
      CI=0.17, 0.67). CONCLUSIONS: Findings highlight the importance of parents
      receiving hands-on education regarding the proper use of age-appropriate child
      restraints.

PMID- 25602902
TI  - The impact of prices and taxes on the use of tobacco products in Latin America
      and the Caribbean.
AB  - We examined the impact of tobacco prices or taxes on tobacco use in Latin America
      and Caribbean countries. We searched MEDLINE, EconLit, LILACS, unpublished
      literature, 6 specialty journals, and reviewed references. We calculated pooled
      price elasticities using random-effects models. The 32 studies we examined found
      that cigarette prices have a negative and statistically significant effect on
      cigarette consumption. A change in price is associated with a less than
      proportional change in the quantity of cigarettes demanded. In most Latin
      American countries, own-price elasticity for cigarettes is likely below  -0.5 
      (pooled elasticities, short-run: -0.31; 95% confidence interval=-0.39, -0.24;
      long-run: -0.43; 95% CI=-0.51, -0.35). Tax increases effectively reduce cigarette
      use. Lack of studies using household- or individual-level data limits research's
      policy relevance.

PMID- 25602903
TI  - Adapting the Crisis Intervention Team (CIT) model of police-mental health
      collaboration in a low-income, post-conflict country: curriculum development in
      Liberia, West Africa.
AB  - OBJECTIVES: We sought to develop a curriculum and collaboration model for law
      enforcement and mental health services in Liberia, West Africa. METHODS: In 2013
      we conducted key informant interviews with law enforcement officers, mental
      health clinicians, and mental health service users in Liberia, and facilitated a
      3-day curriculum workshop. RESULTS: Mental health service users reported prior
      violent interactions with officers. Officers and clinicians identified
      incarceration and lack of treatment of mental health service users as key
      problems, and they jointly drafted a curriculum based upon the Crisis
      Intervention Team (CIT) model adapted for Liberia. Officers' mental health
      knowledge improved from 64% to 82% on workshop assessments (t=5.52; P<.01).
      Clinicians' attitudes improved (t=2.42; P=.03). Six months after the workshop,
      69% of clinicians reported improved engagement with law enforcement. Since the
      Ebola outbreak, law enforcement and clinicians have collaboratively addressed
      diverse public health needs. CONCLUSIONS: Collaborations between law enforcement
      and mental health clinicians can benefit multiple areas of public health, as
      demonstrated by partnerships to improve responses during the Ebola epidemic.
      Future research should evaluate training implementation and outcomes including
      stigma reduction, referrals, and use of force.

PMID- 25602904
TI  - Legal action against health claims on foods and beverages marketed to youth.
AB  - The prevalence of obesity among US children raises numerous health concerns. One
      pathway to reduce childhood obesity is by decreasing energy intake through the
      ingestion of fewer calories. Yet, food and beverage manufacturers often promote
      energy-dense items for children via varied health claims. Deceptive health claims
      are prohibited, and may be addressed through litigation or governmental
      regulatory efforts. While the amount of legal action against these potentially
      deceptive claims has increased, no comprehensive assessment has been conducted.
      This article, which analyzes litigation and governmental regulatory activities,
      considers key factors that may influence decisions to take legal action against
      potentially deceptive health claims on foods and beverages, including scientific
      support, forum selection, selection of plaintiffs, and potential public health
      impact. 

PMID- 25602905
TI  - Cyberbullying perpetration and victimization among middle-school students.
AB  - OBJECTIVES: We examined correlations between gender, race, sexual identity, and
      technology use, and patterns of cyberbullying experiences and behaviors among
      middle-school students. METHODS: We collected a probability sample of 1285
      students alongside the 2012 Youth Risk Behavior Survey in Los Angeles Unified
      School District middle schools. We used logistic regressions to assess the
      correlates of being a cyberbully perpetrator, victim, and perpetrator-victim
      (i.e., bidirectional cyberbullying behavior). RESULTS: In this sample, 6.6%
      reported being a cyberbully victim, 5.0% reported being a perpetrator, and 4.3%
      reported being a perpetrator-victim. Cyberbullying behavior frequently occurred
      on Facebook or via text messaging. Cyberbully perpetrators, victims, and
      perpetrators-victims all were more likely to report using the Internet for at
      least 3 hours per day. Sexual-minority students and students who texted at least
      50 times per day were more likely to report cyberbullying victimization. Girls
      were more likely to report being perpetrators-victims. CONCLUSIONS: Cyberbullying
      interventions should account for gender and sexual identity, as well as the
      possible benefits of educational interventions for intensive Internet users and
      frequent texters.

PMID- 25602906
TI  - RNAa in action: from the exception to the norm.
AB  - Small RNA programmed Argonautes are sophisticated cellular effector platforms
      known to be involved in a diverse array of functions ranging from mRNA cleavage,
      translational inhibition, DNA elimination, epigenetic silencing, alternative
      splicing and even gene activation. First observed in human cells, small RNA
      induced gene activation, also known as RNAa, involves the targeted recruitment of
      Argonaute proteins to specific promoter sequences followed by induction of stable
      epigenetic changes which promote transcription. The existence of RNAa remains
      contentious due to its elusive mechanism. A string of recent studies in C.
      elegans provides unequivocal evidence for RNAa's fundamental role in sculpting
      the epigenetic landscape and maintaining active transcription of endogenous genes
      and supports the presence of a functionally sophisticated network of small RNA
      Argonaute pathways consisting of opposite yet complementary "yin and yang"
      regulatory elements. In this review, we summarize key findings from recent
      studies of endogenous RNAa in C. elegans, with an emphasis on the Argonaute
      protein CSR-1. 

PMID- 25602907
TI  - Is change in availability of sports facilities associated with change in physical
      activity? A prospective cohort study.
AB  - OBJECTIVE: We examined whether change in distance to or number of sports
      facilities is related to change in metabolic equivalent task (MET) hours/week.
      METHOD: 25,834 Finnish Public Sector study cohort participants reported their
      weekly physical activity in 2000 and 2008. Distances from each participant's home
      to the nearest facility and number of facilities within 500m from home were
      calculated from geographic coordinates. We assessed changes in weekly MET hours
      of physical activity between the baseline and the follow-up in relation to change
      in distance to the nearest facility (remained close, decreased, remained distant,
      increased) and number of facilities <500m from home (remained high, increased,
      remained low, decreased). RESULTS: The average decrease in MET hours was greater
      for those whose distance to a sports facility increased (-1.4 (95% CI -3.8-
      0.96)) (vs. remained close). The same was observed for those for whom the number
      of facilities near home decreased (-2.35 (95% CI -4.84-0.14)) (vs. remained
      high). Increase in availability was not related to increase in MET hours.
      CONCLUSIONS: An increase in distance to and decrease in number of sports
      facilities were associated with a decrease in physical activity suggesting that
      changes in availability of facilities may affect physical activity levels.

PMID- 25602908
TI  - Invitation strategies for colorectal cancer screening programmes: The impact of
      an advance notification letter.
AB  - AIM: To estimate the impact of an advance notification letter on participation in
      sigmoidoscopy (FS) and fecal immunochemical test (FIT) screening. METHODS:
      Eligible subjects, invited in 3 Italian population based programmes using FS and
      in 5 using FIT, were randomised (1:1:1), within GP, to: A) standard invitation
      letter; B) advance notification followed after 1month by the standard invitation;
      and C) B+indication to contact the general practitioner (GP) to get advice about
      the decision to be screened. We calculated the 9-month attendance and the
      incremental cost of each strategy. We conducted a phone survey to assess GP's
      utilization and predictors of participation. RESULTS: The advance notification
      was associated with a 20% increase in the attendance among 15,655 people invited
      for FS (B vs A - RR: 1.17, 95% CI: 1.10-1.25; C vs A - RR: 1.19, 95% CI: 1.12
      1.27); the incremental cost ranged between 10 and 9 Euros. Participation in FIT
      screening (N=23,543) was increased only with simple pre-notification (B vs A -
      RR: 1.06, 95% CI: 1.02-1.10); the incremental cost was 22.5 Euros. GP
      consultation rate was not increased in group C. CONCLUSIONS: An advance
      notification represents a cost-effective strategy to increase participation in FS
      screening; its impact on the response to FIT screening was limited.

PMID- 25602909
TI  - Weighing in on the hidden Asian American obesity epidemic.
AB  - According to national estimates, obesity prevalence is lower in Asian Americans
      compared to other racial/ethnic groups, but this low prevalence may be misleading
      for three reasons. First, a lower body mass index (BMI) cutoff as proposed by the
      World Health Organization may be more appropriate to use in Asian populations.
      However, evidence is limited to substantiate the potential costs and burden of
      adopting these cutoffs. Increasing BMI in Asians (as in other racial/ethnic
      groups) should be considered across the spectrum of BMI, with a minimum awareness
      of these lower cutoffs among healthcare researchers. Second, the need for
      disaggregated data across Asian American subgroups is illustrated by the higher
      obesity (and diabetes) prevalence estimates observed in South Asian Americans.
      Third, prevalence of obesity should be placed in the larger context of
      immigration and globalization through cross-national comparisons and examination
      of acculturation-related factors. However these types of studies and collection
      of salient variables are not routinely performed. Data from a metropolitan area
      where many Asian Americans settle is presented as a case study to illustrate
      these points. Clear evidence that incorporates these three considerations is
      necessary for program planning and resource allocation for obesity-related
      disparities in this rapidly growing and diverse population. 

PMID- 25602911
TI  - The geographic distribution of eye care providers in the United States:
      Implications for a national strategy to improve vision health.
AB  - OBJECTIVE: To describe the patterns of local eye care provider availability in
      the US. METHODS: Data from 2011 on the number of ophthalmologists and
      optometrists in each of the 3143 counties in the US were drawn from the Area
      Health Resources File. Population-weighted quartiles of the county-level number
      of ophthalmologists per capita and the county-level number of optometrists per
      capita were defined. Descriptive statistics were calculated and a cross
      tabulation of quartiles of ophthalmologist availability and quartiles of
      optometrist availability was conducted for all the counties in the US and for the
      set of counties in each region of the US. RESULTS: 24.0% of US counties had no
      ophthalmologists or optometrists. 60.7% of counties in the US were in one of the
      lower two quartiles of both ophthalmologist availability and optometrist
      availability, and 24.1% of counties were in one of the lower two quartiles of
      ophthalmologist availability but in one of the upper two quartiles of optometrist
      availability. CONCLUSIONS: Public health interventions that are effective in a
      context of limited local eye care provider availability or that are able to
      leverage optometrist availability effectively in areas with limited
      ophthalmologist availability could be of widespread use in the US.

PMID- 25602910
TI  - The association between muscle strengthening activities and red blood cell
      distribution width among a national sample of U.S. adults.
AB  - Red blood cell distribution width (RDW) is a novel biomarker indicative of
      cardiovascular disease. However, little research has examined the association of
      muscle strengthening activities (MSA) on RDW. OBJECTIVE: Examine the association
      between MSA and RDW among a national sample of U.S. adults. METHODS: Data from
      the 2003-2006 (n=8257) National Health and Nutrition Examination Survey were
      used. Multivariable linear and logistic regression analyses were used to examine
      the association between MSA with RDW. Participants self-reported their extent of
      MSA (e.g., lifting weights, push-ups, and sit-ups) and RDW was assessed from a
      blood sample. RESULTS: Independent of demographics, aerobic-based physical
      activity and established cardiovascular disease risk factors, for every 1 MSA
      session per day increase, the odds of having an elevated RDW (>=14.1%) reduced by
      34% (p<0.05). In alignment with current resistance training guidelines by the
      government, for every increase of 2 MSA sessions per week, participants had an
      11% reduced odds of having an elevated RDW (p=0.006). CONCLUSION: Engagement in
      MSA is inversely associated with RDW. Although speculative, these findings
      suggest that changes in RDW may be one potential mechanism through which MSA may
      influence cardiovascular disease.

PMID- 25602912
TI  - A latent class model to identify city/town chronic disease patterns.
AB  - OBJECTIVE: Most departments of health grapple with how to most effectively
      allocate resources to address chronic diseases. We adapted a model created by
      Massachusetts to create customized city/town profiles in order to identify the
      patterns of chronic disease among 39 cities/towns in Rhode Island. METHODS: We
      used four data sources to identify 20 indicators of four domains: demographics
      and socioeconomic status; health behaviors and chronic diseases prevalence; no
      regular provider and non-emergent emergency department visits; and chronic
      disease-related hospitalizations. A latent class model was used to group
      cities/towns into distinct latent class memberships based on similar patterns of
      indicators. Data were analyzed in 2014. RESULTS: The latent class model
      differentiated three distinct classes of city/town, reflecting three levels of
      economic and health indicators. CONCLUSIONS: Our model was a simplified version
      of one constructed by Massachusetts that larger states can also use to understand
      chronic disease patterns among cities/towns. Chronic disease programs and
      policies can use the findings to direct resources toward targets not always
      identified by more traditional analyses.

PMID- 25602913
TI  - Longitudinal study of acculturation and BMI change among Asian American men.
AB  - BACKGROUND: Cross-sectional studies examining the association between Western
      acculturation and BMI in Asians have been inconsistent, and studies on BMI change
      are lacking. OBJECTIVE: This study examined the associations between indicators
      of acculturation (generational status, length of US residence, and age at
      immigration) and overweight (BMI >=25kg/m(2)) as well as 5-year BMI changes in
      7,073 Chinese, Japanese, Korean, Filipino, and Vietnamese men who lived in the US
      and were 44-71years old at baseline of the California Men's Health Study (2002
      2003). METHODS: Indicators of acculturation were reported at baseline. Repeated
      clinical measures of BMI were extracted from electronic health records (2005
      2012). RESULTS: Using generalized estimating equations we found that lower
      generational status, shorter duration of US residence and older age at
      immigration were inversely associated with being overweight. However, analysis of
      BMI curves using linear mixed models showed that shorter length of US residence
      and older age at immigration were associated with larger 5-year increases in BMI.
      CONCLUSIONS: Asian immigrants who were less acculturated had larger BMI increases
      as they became more acculturated but had not achieved overweight status. Healthy
      weight interventions among Asians immigrants may be most effective when targeting
      weight maintenance early in the process of acculturation.

PMID- 25602914
TI  - The organization of melatonin in lipid membranes.
AB  - Melatonin is a hormone that has been shown to have protective effects in several
      diseases that are associated with cholesterol dysregulation, including
      cardiovascular disease, Alzheimer's disease, and certain types of cancers. We
      studied the interaction of melatonin with model membranes made of
      dimyristoylphosphatidylcholine (DMPC) at melatonin concentrations ranging from
      0.5mol% to 30mol%. From 2-dimensional X-ray diffraction measurements, we find
      that melatonin induces a re-ordering of the lipid membrane that is strongly
      dependent on the melatonin concentration. At low melatonin concentrations, we
      observe the presence of melatonin-enriched patches in the membrane, which are
      significantly thinner than the lipid bilayer. The melatonin molecules were found
      to align parallel to the lipid tails in these patches. At high melatonin
      concentrations of 30mol%, we observe a highly ordered melatonin structure that is
      uniform throughout the membrane, where the melatonin molecules align parallel to
      the bilayers and one melatonin molecule associates with 2 lipid molecules.
      Understanding the organization and interactions of melatonin in membranes, and
      how these are dependent on the concentration, may shed light into its anti
      amyloidogenic, antioxidative and photoprotective properties and help develop a
      structural basis for these properties. 

PMID- 25602915
TI  - The role of the soluble urokinase plasminogen activator (suPAR) in children with
      pneumonia.
AB  - Although pneumonia is one of the most important health problems in children,
      there is still no widely accepted disease severity score, the data on the
      correlation between the conventional inflammatory markers or chest X-ray and the
      disease severity remain disputable, and thus, there is an urgent need for a new
      pneumonia biomarker. The soluble urokinase plasminogen activator (suPAR) is a
      soluble form of the urokinase plasminogen activator that plays an important role
      in the innate host defense in the pulmonary tissue. suPAR levels have been
      associated with a general activation of the immune system rather than with a
      particular etiological factor. suPAR has a high prognostic value in critically
      ill patients, especially with sepsis, but there is a growing number of studies
      focusing on suPAR in respiratory diseases. The aim of this review is to summarize
      the knowledge on the role of the suPAR/uPAR in lung pathology and its possible
      use in pneumonia in children. 

PMID- 25602916
TI  - Compartmental models of the chest wall and the origin of Hoover's sign.
AB  - First, one- and two-compartment models of the chest wall are reviewed. Then, a
      three-compartment model is described, and the predictions of the model are
      compared with data on pressure and volume relationships for different breathing
      maneuvers in dogs. Finally, the three-compartment model is scaled to apply to
      humans, and dynamic solutions for periodic breathing are obtained. To model COPD,
      the area of the zone of apposition is decreased, and to model COPD patients who
      show Hoover's sign, pulmonary resistance and abdominal compliance are increased.
      The resulting traces match those reported by Binazzi et al. (2008. Respir.
      Physiol. Neurobiol. 160: 325-333) for controls and patients with COPD, both
      without and with Hoover's sign. We conclude that Hoover's sign is a dynamic
      phenomenon that results from the decrease in the area of the zone of apposition
      that occurs in COPD and a larger pulmonary resistance and abdominal compliance in
      those patients who show Hoover's sign. 

PMID- 25602917
TI  - Role of in situ resultant H2O2 in the visible-light-driven photocatalytic
      inactivation of E. coli using natural sphalerite: a genetic study.
AB  - This study investigated how a natural sphalerite (NS) photocatalyst, under
      visible light irradiation, supports photocatalytic bacterial inactivation. This
      was done by comparing parent E. coli BW25113, and its two isogenic single-gene
      knock-out mutants, E. coli JW0797-1 (dps(-) mutant) and JW1721-1 (katE(-)
      mutant), where both dps and KatE genes are likely related to H2O2 production. NS
      could inactivate approximately 5-, 7- and 7-log of E. coli BW25113, JW0797-1, and
      JW1721-1 within 6 h irradiation, respectively. The two isogenic mutants were more
      susceptible to photocatalysis than the parental strain because of their lack of a
      defense system against H2O2 oxidative stress. The ability of in situ resultant
      H2O2 to serve as a defense against photocatalytic inactivation was also confirmed
      using scavenging experiments and partition system experiments. Studying catalase
      activity further revealed that in situ H2O2 played an important role in these
      inactivation processes. The destruction of bacterial cells from the cell envelope
      to the intracellular components was also observed using field emission-scanning
      electron microscopy. Moreover, FT-IR was used to monitor bacterial cell
      decomposition, key functional group evolution, and bacterial cell structures.
      This is the first study to investigate the photocatalytic inactivation mechanism
      of E. coli using single-gene deletion mutants under visible light irradiation. 

PMID- 25602918
TI  - Parental monitoring in late adolescence: relations to ADHD symptoms and
      longitudinal predictors.
AB  - In this study, we aimed to replicate Stattin and Kerr's (2000) study on parental
      monitoring and adolescents' deviant behavior, to extend their findings to ADHD
      symptoms, and to examine the longitudinal predictors (8-18 years) of parental
      knowledge and child disclosure. Results showed that conduct problems were
      primarily associated with parental knowledge and child disclosure, but not with
      parental solicitation and control. A similar pattern was observed for ADHD
      symptoms. However, while the relations for conduct problems were generally
      independent of ADHD symptoms, the relations for ADHD symptoms were primarily non
      significant after controlling for conduct problems. Moreover, early behavior
      problems, but not insecure/disorganized attachment, were associated with parental
      knowledge and child disclosure in adolescence. In conclusion, child disclosure is
      primarily associated with deviant behavior rather than ADHD, and early child
      problem behavior is a more important predictor of child disclosure (implicating
      reciprocal relations between these two constructs) than is insecure/disorganized
      attachment. 

PMID- 25602919
TI  - Clustering of CARMA1 through SH3-GUK domain interactions is required for its
      activation of NF-kappaB signalling.
AB  - CARMA1-mediated NF-kappaB activation controls lymphocyte activation through
      antigen receptors and survival of some malignant lymphomas. CARMA1 clusters are
      formed on physiological receptor-mediated activation or by its oncogenic mutation
      in activated B-cell-diffuse large B-cell lymphomas (ABC-DLBCLs) with constitutive
      NF-kappaB activation. However, regulatory mechanisms and relevance of CARMA1
      clusters in the NF-kappaB pathway are unclear. Here we show that SH3 and GUK
      domain interactions of CARMA1 link CARMA1 clustering to signal activation. SH3
      and GUK domains of CARMA1 interact by either intra- or intermolecular mechanisms,
      which are required for activation-induced assembly of CARMA1. Disruption of these
      interactions abolishes the formation of CARMA1 microclusters at the immunological
      synapse, CARMA-regulated signal activation following antigen receptor stimulation
      as well as spontaneous CARMA1 clustering and NF-kappaB activation by the
      oncogenic CARMA1 mutation in ABC-DLBCLs. Thus, the SH3-GUK interactions that
      regulate CARMA1 cluster formations are promising therapeutic targets for ABC
      DLBCLs. 

PMID- 25602920
TI  - Oral administration of hen egg white ovotransferrin attenuates the development of
      colitis induced by dextran sodium sulfate in mice.
AB  - Ovotransferrin (OVT), one of the major hen egg white proteins, was shown to
      possess antimicrobial and antioxidant activities in vitro. However, there is no
      information regarding the in vivo preventative effect in chronic inflammatory
      diseases such as inflammatory bowel disease (IBD). The aim of the present study
      is to evaluate the anti-inflammatory effects of OVT in a mouse model of dextran
      sodium sulfate (DSS)-induced colitis. OVT (50 or 250 mg/kg BW) was given orally
      for 14 days to female BALB/c mice, and 5% DSS (MW 36-50 kDa) was used to induce
      acute colitis (days 7-14) via drinking water. The current in vivo study
      demonstrated that OVT significantly reduced clinical signs, weight loss,
      shortening of the colon, and inflammatory cytokine markers of disease. The
      histopathological analysis of the colon revealed that OVT reduced histological
      scores. These results indicate that the use of OVT may be a potential promising
      candidate for the prevention of IBD. 

PMID- 25602921
TI  - Application of a new methodology for coastal multi-hazard-assessment & management
      on the state of Karnataka, India.
AB  - This paper presents the application of a new methodology for coastal multi-hazard
      assessment & management under a changing global climate on the state of
      Karnataka, India. The recently published methodology termed the Coastal Hazard
      Wheel (CHW) is designed for local, regional and national hazard screening in
      areas with limited data availability, and covers the hazards of ecosystem
      disruption, gradual inundation, salt water intrusion, erosion and flooding. The
      application makes use of published geophysical data and remote sensing
      information and is showcasing how the CHW framework can be applied at a scale
      relevant for regional planning purposes. It uses a GIS approach to develop
      regional and sub-regional hazard maps as well as to produce relevant hazard risk
      data, and includes a discussion of uncertainties, limitations and management
      perspectives. The hazard assessment shows that 61 percent of Karnataka's
      coastline has a high or very high inherent hazard of erosion, making erosion the
      most prevalent coastal hazard. The hazards of flooding and salt water intrusion
      are also relatively widespread as 39 percent of Karnataka's coastline has a high
      or very high inherent hazard for both of these hazard types. 

PMID- 25602922
TI  - Integration of ecosystem services into the carbon footprint of milk of South
      German dairy farms.
AB  - Allocation of greenhouse gas emissions (GHG) in Life Cycle Assessments (LCA) is
      challenging especially when multi-functionality of dairy farms, which do not only
      produce milk but also meat is considered. Moreover, some farms fulfill a wide
      range of additional services for society such as management of renewable natural
      resources as well as preservation of biodiversity and cultural landscapes. Due to
      the increasing degradation of ecosystems many industrialized as well as
      developing countries designed payment systems for environmental services. This
      study examines different allocation methods of GHG for a comparatively large
      convenience sample of 113 dairy farms located in grassland-based areas of
      southern Germany. Results are carbon footprints of 1.99 kg CO2eq/kg of fat and
      protein corrected milk (FPCM) on average if "no allocation" for coupled products
      is performed. "Physical allocation" results in 1.53 kg CO2eq/kg FPCM and
      "conventional economic allocation" in 1.66 kg CO2eq/kg FPCM on average if
      emissions are apportioned between milk and meat. Economic allocation which
      includes ecosystem services for society based on the farm net income as a new
      aspect in this study results in a carbon footprint of 1.5 kg CO2eq/kg FPCM on
      average. System expansion that puts greater emphasis on coupled beef production
      accounts for a carbon footprint of 0.68 kg CO2eq/kg FPCM on average. Intense milk
      production systems with higher milk yields show better results based on "no
      allocation", "physical allocation" and "conventional economic allocation". By
      contrast, economic allocation, which takes into account ecosystem services favors
      extensive systems, especially in less favored areas. This shows that carbon
      footprints of dairy farms should not be examined one-dimensionally based on the
      amount of milk and meat that is produced on the farm. Rather, a broader
      perspective is necessary that takes into account the multi-functionality of dairy
      farms especially in countries where a wide range of ecosystem services is
      provided. 

PMID- 25602923
TI  - Recovery of ammonia from swine manure using gas-permeable membranes: effect of
      aeration.
AB  - The gas-permeable membrane process can recover ammonia from manure, reducing
      pollution whilst converting ammonia into an ammonium salt fertilizer. The process
      involves manure pH control to increase ammonium (NH4(+)) recovery rate that is
      normally carried out using an alkali. In this study a new strategy to avoid the
      use of alkali was tested applying low-rate aeration and nitrification inhibition.
      The wastewater used was raw swine manure with 2390 mg NH4(+)-N/L. Results showed
      that aeration increased pH above 8.5 allowing quick transformation of NH4(+) into
      gaseous ammonia (NH3) and efficient recovery by permeation through the submerged
      membrane. The overall NH4(+) recovery obtained with aeration was 98% and ammonia
      emissions losses were less than 1.5%. The new approach can substitute large
      amounts of alkali chemicals needed to obtain high NH4(+) recovery with important
      economic and environmental savings. 

PMID- 25602924
TI  - Solid olive waste in environmental cleanup: enhanced nitrite ion removal by ZnCl2
      activated carbon.
AB  - This communication describes how olive solid wastes can be used to prepare
      activated carbon (AC), with soundly high surface areas, suitable to remove
      nitrite ions from water. Solid olive wastes, so called Jeft, separated as
      unwanted bi-products from olive oil mills, have been converted into charcoal. The
      charcoal was then physically and/or chemically activated using different
      compounds namely conc. H3PO4 or ZnCl2. Charcoal carbonization was performed under
      inert atmosphere to avoid loss of heated carbon by oxidation with air. Surface
      area measurements and SEM micrographs showed that activation using ZnCl2 yields
      AC with highest surface area and more porous surfaces. The ZnCl2-activated carbon
      was then used to remove nitrite ions from water by adsorption. Effects of
      different parameters on value of surface area and adsorption capacity of the AC
      were investigated. Commercial AC materials were used as reference for comparison.
      The AC showed higher adsorption capacity toward nitrite than other reported
      adsorbents. The results suggest that using 5 g of the ZnCl2-activated carbon per
      liter of heavily nitrite-contaminated water (50 ppm) may bring the contaminant
      concentration down to the WHO accepted concentration limits within 60 min. This
      work highlights the future feasibility of using olive waste as feed stocks to
      produce useful renewable materials while keeping in mind the wisdom "make wastes
      work in environmental protection".

PMID- 25602925
TI  - Neurobehavioral effects of concurrent exposure to cesium-137 and paraquat during
      neonatal development in mice.
AB  - As a result of nuclear power plants accidents such as Chernobyl or Fukushima,
      some people were exposed to external and internal ionizing radiation (IR). Human
      brain is highly sensitive to IR during fetal and postnatal period when the
      molecular processes are not completely finished. Various studies have shown that
      exposure to low doses of IR causes a higher incidence of cognitive impairment. On
      the other hand, in industrialized countries, people are daily exposed to a number
      of toxicant pollutants. Exposure to environmental chemicals, such as paraquat
      (PQ), may potentiate the toxic effects induced by radiation on brain development.
      In this study, we evaluated the cognitive effects of concomitant exposure to low
      doses of internal radiation ((137)Cs) and PQ during neonatal brain development.
      At the postnatal day 10 (PND10), two groups of mice (C57BL/6J) were exposed to
      (137)Cs (4000 and 8000 Bq/kg) and/or PQ (7 mg/kg). To investigate the spontaneous
      behavior, learning, memory capacities and anxiety, behavioral tests were
      conducted in the offspring at two months of age. The results showed that
      cognitive functions were not significantly affected when (137)Cs or PQ were
      administered alone. However, alterations in the working memory and anxiety were
      detected in mice exposed to (137)Cs combined with PQ.

PMID- 25602927
TI  - Facile solid-phase parallel synthesis of linear and cyclic peptoids for
      comparative studies of biological activity.
AB  - A series of linear and cyclic peptoids, which were expected to possess better
      pharmacokinetic properties and biological activities for blocking the interaction
      between apolipoprotein E and amyloid-beta, were designed and synthesized as
      possible therapeutic agents. Peptoids were easily synthesized on solid-phase by
      the submonomer strategy and polar side chain-containing amines were effectively
      introduced under the modified reaction conditions. For the synthesis of cyclic
      peptoids, beta-alanine protected with the 2-phenylisopropyl group, which could be
      selectively removed by 2% TFA, was used as a primary amine to afford a complete
      peptoid unit. The macrolactamization between the carboxylic acid of beta-alanine
      moiety and terminal amine of peptoids was successfully performed in the presence
      of the PyAOP coupling agent on solid-phase in all the cases, providing various
      sizes of cyclic peptoids. In particular, some cyclic peptoids prepared in this
      study are the largest in size among cyclic peptoids reported to date. The
      synthetic strategy which was adopted in this study can also provide a robust
      platform for solid-phase construction of cyclic peptoid libraries. Currently,
      synthetic peptoids have been used to test interesting biological activities
      including the ApoE/Abeta interaction inhibition, nontoxicity, the blood-brain
      barrier permeability, etc. 

PMID- 25602926
TI  - Pushing the envelope in tissue engineering: ex vivo production of thick
      vascularized cardiac extracellular matrix constructs.
AB  - Functional vascularization is a prerequisite for cardiac tissue engineering of
      constructs with physiological thicknesses. We previously reported the successful
      preservation of main vascular conduits in isolated thick acellular porcine
      cardiac ventricular ECM (pcECM). We now unveil this scaffold's potential in
      supporting human cardiomyocytes and promoting new blood vessel development ex
      vivo, providing long-term cell support in the construct bulk. A custom-designed
      perfusion bioreactor was developed to remodel such vascularization ex vivo,
      demonstrating, for the first time, functional angiogenesis in vitro with various
      stages of vessel maturation supporting up to 1.7 mm thick constructs. A robust
      methodology was developed to assess the pcECM maximal cell capacity, which
      resembled the human heart cell density. Taken together these results demonstrate
      feasibility of producing physiological-like constructs such as the thick pcECM
      suggested here as a prospective treatment for end-stage heart failure.
      Methodologies reported herein may also benefit other tissues, offering a valuable
      in vitro setting for "thick-tissue" engineering strategies toward large animal in
      vivo studies. 

PMID- 25602928
TI  - Impaired extinction of fear conditioning after REM deprivation is magnified by
      rearing in an enriched environment.
AB  - Evidence from both human and animal studies indicates that rapid eye movement
      sleep (REM) is essential for the acquisition and retention of information,
      particularly of an emotional nature. Learning and memory can also be impacted by
      manipulation of housing condition such as exposure to an enriched environment
      (EE). This study investigated the effects of REM deprivation and EE, both
      separately and combined, on the extinction of conditioned fear in rats.
      Consistent with prior studies, conditioning was enhanced in EE-reared rats and
      extinction was impaired in REM deprived rats. In addition, rats exposed to both
      REM deprivation and EE showed the greatest impairment in extinction, with effects
      persisting through the first two days of extinction training. This study is the
      first to explore the combination of REM deprivation and EE and suggests that
      manipulations that alter sleep, particularly REM, can have persisting deleterious
      effects on emotional memory processing. 

PMID- 25602929
TI  - REM sleep and memory reorganization: Potential relevance for psychiatry and
      psychotherapy.
AB  - Sleep can foster the reorganization of memory, i.e. the emergence of new memory
      content that has not directly been encoded. Current neurophysiological and
      behavioral evidence can be integrated into a model positing that REM sleep
      particularly promotes the disintegration of existing schemas and their
      recombination in the form of associative thinking, creativity and the shaping of
      emotional memory. Particularly, REM sleep related dreaming might represent a
      mentation correlate for the reconfiguration of memory. In a final section, the
      potential relevance for psychiatry and psychotherapy is discussed. 

PMID- 25602930
TI  - Orthorexia Nervosa in Turkish Dietitians.
AB  - The purpose of this study was to determine the prevalence of orthorexia nervosa
      in dietitians, as assessed by administering ORTO-15, Eating Attitudes Test-40
      (EAT-40) and Maudsley Obsessive-Compulsive Inventory (MOCI). Our study included
      117 dietitians (Ankara). Orto-15 test scores below 40 points was considered
      indicative of orthorexia, while higher scores indicated a normal eating behavior.
      It was found that participants with ORTO-15 scores less than 40 had higher scores
      for EAT-40 and MOCI (p < 0.05). The results showed a significant negative
      correlation between the ORTO-15 and EAT-40 scores and BMI values. In that
      respect, further investigation with dietitians into orthorexia nervosa is
      recommended. 

PMID- 25602931
TI  - Multiple myeloma.

PMID- 25602932
TI  - Synthesis and pharmacological evaluation of benzannulated derivatives as potent
      and selective sigma-1 protein ligands.
AB  - The sigma1 proteins are considered to be a new class of target structures for
      several central nervous system disorders, including depression, anxiety,
      psychosis, and Parkinson's and Alzheimer's diseases. Recently, the involvement of
      these receptors in neuropathic pain and cancer has also been observed. So far,
      only a few ligands are in clinical trials. In a continuation of our previous
      studies on the development of sigma1 ligands, a new series of benzannulated
      heterocycles was designed and synthesised. In vitro competition binding assays
      showed that many of them possessed high sigma1 receptor affinity (Ki = 0.6-10.3
      nM), and good sigma2/sigma1 subtype selectivity, without cytotoxic effects on
      SY5Y cells (human neuroblastoma cell line). 

PMID- 25602933
TI  - Design, synthesis and cytotoxic evaluation of 4-methylidenepyrazolidin-3-ones.
AB  - Three series of new 4-methylidenepyrazolidin-3-ones with various substitution
      patterns were synthesized and tested for the cytotoxic activity against two human
      leukemia cell lines NALM-6 and HL-60 as well as MCF-7 breast cancer cell line.
      Several obtained methylidenepyrazolidinones exhibited high cytotoxic activity
      with IC50 values below 10 MUM, mainly against HL-60 leukemia cell line and two of
      them, 18d,e, displayed IC50 <= 5 MUM, against all tested cell lines. Structure
      activity relationship studies revealed that the presence of phenyl substituents
      on both ring nitrogen atoms and vinyl or phenyl substituents in position 5 are
      crucial for high activity. Selected methylidenepyrazolidinones were also tested
      on normal human umbilical vein endothelial cells (HUVEC) and pyrazolidinone 18a
      was found to be 5-fold more toxic against HL-60 than normal cells. 

PMID- 25602934
TI  - Comment on "Structural characterization of dissolved organic matter: a review of
      current techniques for isolation and analysis" by E. C. Minor, M. M. Swenson, B.
      M. Mattson, and A. R. Oyler, Environ. Sci.: Processes Impacts, 2014, 16, 2064.

PMID- 25602935
TI  - Synthesis and tau RNA binding evaluation of ametantrone-containing ligands.
AB  - We describe the synthesis and characterization of ametantrone-containing RNA
      ligands based on the derivatization of this intercalator with two neamine
      moieties (Amt-Nea,Nea) or with one azaquinolone heterocycle and one neamine (Amt
      Nea,Azq) as well as its combination with guanidinoneamine (Amt-NeaG4).
      Biophysical studies revealed that guanidinylation of the parent ligand (Amt-Nea)
      had a positive effect on the binding of the resulting compound for Tau pre-mRNA
      target as well as on the stabilization upon complexation of some of the mutated
      RNA sequences associated with the development of tauopathies. Further studies by
      NMR revealed the existence of a preferred binding site in the stem-loop
      structure, in which ametantrone intercalates in the characteristic bulged region.
      Regarding doubly-functionalized ligands, binding affinity and stabilizing ability
      of Amt-Nea,Nea were similar to those of the guanidinylated ligand, but the two
      aminoglycoside fragments seem to interfere with its accommodation in a single
      binding site. However, Amt-Nea,Azq binds at the bulged region in a similar way
      than Amt-NeaG4. Overall, these results provide new insights on fine-tuning RNA
      binding properties of ametantrone by single or double derivatization with other
      RNA recognition motifs, which could help in the future design of new ligands with
      improved selectivity for disease-causing RNA molecules. 

PMID- 25602936
TI  - The complex nature of family support across the life span: Implications for
      psychological well-being.
AB  - This study examines the complex role of family networks in shaping adult
      psychological well-being over time. We examine the unique and interactive
      longitudinal influences of family structure (i.e., composition and size) and
      negative family relationship quality on psychological well-being among young
      (ages 18-34), middle-aged (ages 35-49), and older adults (ages 50+). A sample of
      881 adults (72% White; 26% Black) was drawn from the longitudinal Social
      Relations, Age, and Health Study. Structural equation modeling indicated that
      among young and middle-aged adults, increasing family negativity was associated
      with increases in depressive symptoms over time. In contrast, among older adults,
      lowered proportion of family in network and an increasing number of family
      members in the network (i.e., family size) were associated with decreases in
      depressive symptoms. These findings were moderated by family negativity. Among
      older adults with low family negativity, having a lower proportion of family and
      larger family size were associated with decreasing depressive symptoms, but there
      was no effect among those reporting high family negativity. Overall, these
      results contribute to an increased understanding of the complex, developmental
      nature of how family support influences well-being across the life span and
      highlights unique age differences.

PMID- 25602937
TI  - The role of parenting in the prediction of criminal involvement: findings from a
      nationally representative sample of youth and a sample of adopted youth.
AB  - The role of parenting in the development of criminal behavior has been the source
      of a vast amount of research, with the majority of studies detecting
      statistically significant associations between dimensions of parenting and
      measures of criminal involvement. An emerging group of scholars, however, has
      drawn attention to the methodological limitations-mainly genetic confounding-of
      the parental socialization literature. The current study addressed this
      limitation by analyzing a sample of adoptees to assess the association between 8
      parenting measures and 4 criminal justice outcome measures. The results revealed
      very little evidence of parental socialization effects on criminal behavior
      before controlling for genetic confounding and no evidence of parental
      socialization effects on criminal involvement after controlling for genetic
      confounding.

PMID- 25602939
TI  - Orthometalation of dibenzo[1,2]quinoxaline with ruthenium(II/III),
      osmium(II/III/IV), and rhodium(III) ions and orthometalated [RuNO](6/7)
      derivatives.
AB  - A new family of organometallics of ruthenium(II/III), osmium(II/III/IV), and
      rhodium(III) ions isolated from C-H activation reactions of
      dibenzo[1,2]quinoxaline (DBQ) using triphenylphosphine, carbonyl, and halides as
      coligands is reported. The CN-chelate complexes isolated are trans
      [Ru(III)(DBQ)(PPh3)2Cl2] (1), trans-[Ru(II)(DBQ)(CO)(PPh3)2Cl] (2), trans
      [Os(III)(DBQ)(PPh3)2Br2] (3), trans-[Os(II)(DBQ)(PPh3)2(CO)Br] (4), and trans
      [Rh(III)(DBQ)(PPh3)2Cl2] (5). Reaction of 1 with NO affords trans
      [Ru(DBQ)(NO)(PPh3)2Cl]Cl (6(+)Cl(-)), isoelectronic to 2, with a byproduct,
      [Ru(NO)(PPh3)2Cl3] (7). Complexes 1-5 and 6(+) were characterized by elemental
      analyses, mass, IR, NMR, and electron paramagnetic resonance (EPR) spectra
      including the single-crystal X-ray structure determinations of 1-3 and 5. The
      Ru(III)-C, Ru(II)-C, Os(III)-C, and Rh(III)-C lengths are 2.049(2), 2.074(3),
      2.105(16), and 2.012(3) A in 1, 2, 3, and 5. In cyclic voltammetry, 2, 3, and 4
      undergo oxidation at 0.59, 0.39, and 0.46 V, versus Fc(+)/Fc couple, to trans
      [Ru(III)(DBQ)(CO)(PPh3)2Cl](+) (2(+)), trans-[Os(IV)(DBQ)(PPh3)2Br2](+) (3(+)),
      and trans-[Os(III)(DBQ)(CO)(PPh3)2Br](+) (4(+)) ions. Complex 3(+) incorporates
      an Os(IV)(d(4) ion)-C bond. The 6(+)/trans-[Ru(DBQ)(NO)(PPh3)2Cl] (6) reduction
      couple at -0.65 V is reversible. 2(+), 3(+), 4(+) and 6 were substantiated by
      spectroelectrochemical measurements, EPR spectra, and density functional theory
      (DFT) and time-dependent (TD) DFT calculations. The frozen-glass EPR spectrum of
      the electrogenerated 6 exhibits hyperfine couplings due to (99,101)Ru and (14)N
      nuclei. DFT calculations on trans-[Os(III)(DBQ)(PMe3)2Br2] (3(Me)), St = 1/2 and
      trans-[Os(IV)(DBQ)(PMe3)2Br2](+) (3(Me+)), St = 0, trans
      [Ru(DBQ)(NO)(PMe3)2Cl](+) (6(Me+)), St = 0 and trans-[Ru(DBQ)(NO)(PMe3)2Cl]
      (6(Me)), St = 1/2, authenticated a significant mixing between dOs and piaromatic*
      orbitals, which stabilizes M(II/III/IV)-C bonds and the [RuNO](6) and [RuNO](7)
      states, respectively, in 6(+) and 6, which is defined as a hybrid state of trans
      [Ru(II)(DBQ)(NO(*))(PPh3)2Cl] and trans-[Ru(I)(DBQ)(NO(+))(PPh3)2Cl] states. 

PMID- 25602938
TI  - The development of categorization: effects of classification and inference
      training on category representation.
AB  - Does category representation change in the course of development? And if so, how
      and why? The current study attempted to answer these questions by examining
      category learning and category representation. In Experiment 1, 4-year-olds, 6
      year-olds, and adults were trained with either a classification task or an
      inference task and their categorization performance and memory for items were
      tested. Adults and 6-year-olds exhibited an important asymmetry: they relied on a
      single deterministic feature during classification training, but not during
      inference training. In contrast, regardless of the training condition, 4-year
      olds relied on multiple probabilistic features. In Experiment 2, 4-year-olds were
      presented with classification training and their attention was explicitly
      directed to the deterministic feature. Under this condition, their categorization
      performance was similar to that of older participants in Experiment 1, yet their
      memory performance pointed to a similarity-based representation, which was
      similar to that of 4-year-olds in Experiment 1. These results are discussed in
      relation to theories of categorization and the role of selective attention in the
      development of category learning.

PMID- 25602940
TI  - Monoclonal antibody-targeted fluorescein-5-isothiocyanate-labeled biomimetic
      nanoapatites: a promising fluorescent probe for imaging applications.
AB  - Multifunctional biomimetic nanoparticles (NPs) are acquiring increasing interest
      as carriers in medicine and basic research since they can efficiently combine
      labels for subsequent tracking, moieties for specific cell targeting, and
      bioactive molecules, e.g., drugs. In particular, because of their easy synthesis,
      low cost, good biocompatibility, high resorbability, easy surface
      functionalization, and pH-dependent solubility, nanocrystalline apatites are
      promising candidates as nanocarriers. This work describes the synthesis and
      characterization of bioinspired apatite nanoparticles to be used as fluorescent
      nanocarriers targeted against the Met/hepatocyte growth factor receptor, which is
      considered a tumor associated cell surface marker of many cancers. To this aim
      the nanoparticles have been labeled with Fluorescein-5-isothiocyanate (FITC) by
      simple isothermal adsorption, in the absence of organic, possibly toxic,
      molecules, and then functionalized with a monoclonal antibody (mAb) directed
      against such a receptor. Direct labeling of the nanoparticles allowed tracking
      the moieties with spatiotemporal resolution and thus following their interaction
      with cells, expressing or not the targeted receptor, as well as their fate in
      vitro. Cytofluorometry and confocal microscopy experiments showed that the
      functionalized nanocarriers, which emitted a strong fluorescent signal, were
      rapidly and specifically internalized in cells expressing the receptor. Indeed,
      we found that, once inside the cells expressing the receptor, mAb-functionalized
      FITC nanoparticles partially dissociated in their two components, with some mAbs
      being recycled to the cell surface and the FITC-labeled nanoparticles remaining
      in the cytosol. This work thus shows that FITC-labeled nanoapatites are very
      promising probes for targeted cell imaging applications. 

PMID- 25602941
TI  - First results from the oil sands passive air monitoring network for polycyclic
      aromatic compounds.
AB  - Results are reported from an ongoing passive air monitoring study for polycyclic
      aromatic compounds (PACs) in the Athabasca oil sands region in Alberta, Canada.
      Polyurethane foam (PUF) disk passive air samplers were deployed for consecutive 2
      month periods from November 2010 to June 2012 at 17 sites. Samples were analyzed
      for polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, dibenzothiophene and
      its alkylated derivatives (DBTs). Relative to parent PAHs, alkylated PAHs and
      DBTs are enriched in bitumen and therefore considered to be petrogenic markers.
      Concentrations in air were in the range 0.03-210 ng/m(3), 0.15-230 ng/m(3) and
      0.01-61 ng/m(3) for ?PAHs, ?alkylated PAHs and SigmaDBTs, respectively. An
      exponential decline of the PAC concentrations in air with distance from mining
      areas and related petrogenic sources was observed. The most significant
      exponential declines were for the alkylated PAHs and DBTs and attributed to their
      association with mining-related emissions and near-source deposition, due to
      their lower volatility and greater association with depositing particles.
      Seasonal trends in concentrations in air for PACs were not observed for any of
      the compound classes. However, a forest fire episode during April to July 2011
      resulted in greatly elevated PAH levels at all passive sampling locations.
      Alkylated PAHs and DBTs were not elevated during the forest fire period,
      supporting their association with petrogenic sources. Based on the results of
      this study, an "Athabasca PAC profile" is proposed as a potential source marker
      for the oil sands region. The profile is characterized by ?PAHs/?Alkylated PAHs =
      ~0.2 and ?PAHs/?DBTs = ~5. 

PMID- 25602942
TI  - Are common mental disorders more prevalent in the UK serving military compared to
      the general working population?
AB  - BACKGROUND: Although the military is considered to be a stressful occupation,
      there are remarkably few studies that compare the prevalence of common mental
      disorder (CMD) between the military and the general population. This study
      examined the prevalence of probable CMD in a serving UK military sample compared
      to a general population sample of employed individuals. METHOD: Data for the
      general population was from the 2003 and 2008 collections for the Health Survey
      for England (HSE) and for the serving military from phases 1 (2004-2006) and 2
      (2007-2009) of the King's Centre for Military Health Research (KCMHR) cohort
      study. Probable CMD was assessed by the General Health Questionnaire (GHQ-12).
      The datasets were appended to calculate the odds of CMD in the military compared
      to the general population. RESULTS: The odds of probable CMD was approximately
      double in the military, when comparing phase 1 of the military study to the 2003
      HSE [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.1-2.7], and phase 2 to
      the 2008 HSE (OR 2.3, 95% CI 2.0-2.6) after adjustment for sex, age, social
      class, education and marital status. CONCLUSIONS: Serving military personnel are
      more likely to endorse symptoms of CMD compared to those selected from a general
      population study as employed in other occupations, even after accounting for
      demographic characteristics. This difference may be partly explained by the
      context of the military study, with evidence from previous research for higher
      reports of symptoms from the GHQ in occupational compared to population studies,
      in addition to the role of predisposing characteristics.

PMID- 25602943
TI  - Emotion recognition impairment in traumatic brain injury compared with
      schizophrenia spectrum: similar deficits with different origins.
AB  - The aim of our study was to identify the common and separate mechanisms that
      might underpin emotion recognition impairment in patients with traumatic brain
      injury (TBI) and schizophrenia (Sz) compared with healthy controls (HCs). We
      recruited 21 Sz outpatients, 24 severe TBI outpatients, and 38 HCs, and we used
      eye-tracking to compare facial emotion processing performance. Both Sz and TBI
      patients were significantly poorer at recognizing facial emotions compared with
      HC. Sz patients showed a different way of exploring the Pictures of Facial
      Affects stimuli and were significantly worse in recognition of neutral
      expressions. Selective or sustained attention deficits in TBI may reduce
      efficient emotion recognition, whereas in Sz, there is a more strategic deficit
      underlying the observed problem. There would seem to be scope for adjustment of
      effective rehabilitative training focused on emotion recognition. 

PMID- 25602944
TI  - Analysis of genetic code ambiguity arising from nematode-specific misacylated
      tRNAs.
AB  - The faithful translation of the genetic code requires the highly accurate
      aminoacylation of transfer RNAs (tRNAs). However, it has been shown that nematode
      specific V-arm-containing tRNAs (nev-tRNAs) are misacylated with leucine in vitro
      in a manner that transgresses the genetic code. nev-tRNA(Gly) (CCC) and nev
      tRNA(Ile) (UAU), which are the major nev-tRNA isotypes, could theoretically
      decode the glycine (GGG) codon and isoleucine (AUA) codon as leucine, causing GGG
      and AUA codon ambiguity in nematode cells. To test this hypothesis, we
      investigated the functionality of nev-tRNAs and their impact on the proteome of
      Caenorhabditis elegans. Analysis of the nucleotide sequences in the 3' end
      regions of the nev-tRNAs showed that they had matured correctly, with the
      addition of CCA, which is a crucial posttranscriptional modification required for
      tRNA aminoacylation. The nuclear export of nev-tRNAs was confirmed with an
      analysis of their subcellular localization. These results show that nev-tRNAs are
      processed to their mature forms like common tRNAs and are available for
      translation. However, a whole-cell proteome analysis found no detectable level of
      nev-tRNA-induced mistranslation in C. elegans cells, suggesting that the genetic
      code is not ambiguous, at least under normal growth conditions. Our findings
      indicate that the translational fidelity of the nematode genetic code is strictly
      maintained, contrary to our expectations, although deviant tRNAs with
      misacylation properties are highly conserved in the nematode genome.

PMID- 25602945
TI  - Cardiovascular diseases and vulnerable plaques: data, modeling, predictions and
      clinical applications.

PMID- 25602946
TI  - Contemporary issues in rheumatic fever and chronic rheumatic heart disease.

PMID- 25602947
TI  - Advances in therapeutic interventions for patients with pulmonary arterial
      hypertension.

PMID- 25602949
TI  - Histopathological basis of myocardial late gadolinium enhancement in patients
      with systemic hypertension.

PMID- 25602950
TI  - Benign intramyocardial mesothelial cyst in the right ventricular outflow tract:
      computed tomography and cardiovascular magnetic resonance imaging appearances.

PMID- 25602951
TI  - Cardiology Patient Page: inflammation and myocardial infarction.

PMID- 25602952
TI  - Letter by Culic and Fabijanic regarding article, "visible age-related signs and
      risk of ischemic heart disease in the general population: a prospective cohort
      study".

PMID- 25602954
TI  - Letter by Einstein regarding article "comparison of cardiovascular magnetic
      resonance and single-photon emission computed tomography in women with suspected
      coronary artery disease from the Clinical Evaluation of Magnetic Resonance
      Imaging in Coronary Heart Disease (CE-MARC) trial".

PMID- 25602953
TI  - Response to letter regarding article, "visible age-related signs and risk of
      ischemic heart disease in the general population: a prospective cohort study".

PMID- 25602955
TI  - Response to letter regarding article "comparison of cardiovascular magnetic
      resonance and single-photon emission computed tomography in women with suspected
      coronary artery disease from the Clinical Evaluation of Magnetic Resonance
      Imaging in Coronary Heart Disease (CE-MARC) trial".

PMID- 25602956
TI  - Integration of retinal and extraretinal information across eye movements.
AB  - Visual perception is burdened with a highly discontinuous input stream arising
      from saccadic eye movements. For successful integration into a coherent
      representation, the visuomotor system needs to deal with these self-induced
      perceptual changes and distinguish them from external motion. Forward models are
      one way to solve this problem where the brain uses internal monitoring signals
      associated with oculomotor commands to predict the visual consequences of
      corresponding eye movements during active exploration. Visual scenes typically
      contain a rich structure of spatial relational information, providing additional
      cues that may help disambiguate self-induced from external changes of perceptual
      input. We reasoned that a weighted integration of these two inherently noisy
      sources of information should lead to better perceptual estimates. Volunteer
      subjects performed a simple perceptual decision on the apparent displacement of a
      visual target, jumping unpredictably in sync with a saccadic eye movement. In a
      critical test condition, the target was presented together with a flanker object,
      where perceptual decisions could take into account the spatial distance between
      target and flanker object. Here, precision was better compared to control
      conditions in which target displacements could only be estimated from either
      extraretinal or visual relational information alone. Our findings suggest that
      under natural conditions, integration of visual space across eye movements is
      based upon close to optimal integration of both retinal and extraretinal pieces
      of information. 

PMID- 25602957
TI  - Biochemical, histopathological and morphological profiling of a rat model of
      early immune stimulation: relation to psychopathology.
AB  - Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent
      immune dysregulation and abnormal behaviour, which have been shown to have
      translational validity to findings in human neuropsychiatric disorders (e.g.
      schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and
      Alzheimer's disease). The aim of this animal study was to elucidate the influence
      of early immune stimulation triggered by systemic postnatal lipopolysaccharide
      administration on biochemical, histopathological and morphological measures,
      which may be relevant to the neurobiology of human psychopathology. In the
      present study of adult male Wistar rats we examined the brain and plasma levels
      of monoamines (dopamine, serotonin), their metabolites, the levels of the main
      excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid
      and the levels of tryptophan and its metabolites from the kynurenine catabolic
      pathway. Further, we focused on histopathological and morphological markers
      related to pathogenesis of brain diseases--glial cell activation,
      neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the
      substantia nigra. Our results show that early immune stimulation in adult animals
      alters the levels of neurotransmitters and their metabolites, activates the
      kynurenine pathway of tryptophan metabolism and leads to astrogliosis,
      hippocampal volume reduction and a decrease of tyrosine hydroxylase
      immunoreactivity in the substantia nigra. These findings support the crucial
      pathophysiological role of early immune stimulation in the above mentioned
      neuropsychiatric disorders.

PMID- 25602958
TI  - RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins
      in human cells.
AB  - Though RecQL4 was shown to be essential for the initiation of DNA replication in
      mammalian cells, its role in initiation is poorly understood. Here, we show that
      RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical
      interactions and association with replication origins are controlled by the
      concerted action of both CDK and DDK activities. Although RecQL4-dependent
      binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre
      replicative complex, their association with replication origins requires the
      presence of the pre-replicative complex and CDK and DDK activities. Their
      association with replication origins and physical interactions are also targets
      of the DNA damage checkpoint pathways which prevent initiation of DNA replication
      at replication origins. Taken together, the RecQL4-dependent association of Mcm10
      and Ctf4 with replication origins appears to be the first important step
      controlled by S phase promoting kinases and checkpoint pathways for the
      initiation of DNA replication in human cells. 

PMID- 25602959
TI  - Application of a novel population of multipotent stem cells derived from skin
      fibroblasts as donor cells in bovine SCNT.
AB  - Undifferentiated stem cells are better donor cells for somatic cell nuclear
      transfer (SCNT), resulting in more offspring than more differentiated cells.
      While various stem cell populations have been confirmed to exist in the skin,
      progress has been restricted due to the lack of a suitable marker for their
      prospective isolation. To address this fundamental issue, a marker is required
      that could unambiguously prove the differentiation state of the donor cells. We
      therefore utilized magnetic activated cell sorting (MACS) to separate a
      homogeneous population of small SSEA-4(+) cells from a heterogeneous population
      of bovine embryonic skin fibroblasts (BEF). SSEA-4(+) cells were 8-10 MUm in
      diameter and positive for alkaline phosphatase (AP). The percentage of SSEA-4(+)
      cells within the cultured BEF population was low (2-3%). Immunocytochemistry and
      PCR analyses revealed that SSEA-4(+) cells expressed pluripotency-related
      markers, and could differentiate into cells comprising all three germ layers in
      vitro. They remained undifferentiated over 20 passages in suspension culture. In
      addition, cloned embryos derived from SSEA-4 cells showed significant differences
      in cleavage rate and blastocyst development when compared with those from BEF and
      SSEA-4(-) cells. Moreover, blastocysts derived from SSEA-4(+) cells showed a
      higher total cell number and lower apoptotic index as compared to BEF and SSEA-4(
      ) derived cells. It is well known that nuclei from pluripotent stem cells yield a
      higher cloning efficiency than those from adult somatic cells, however,
      pluripotent stem cells are relatively difficult to obtain from bovine. The SSEA
      4(+) cells described in the current study provide an attractive candidate for
      SCNT and a promising platform for the generation of transgenic cattle.

PMID- 25602960
TI  - Regulated expression of a cytokinin biosynthesis gene IPT delays leaf senescence
      and improves yield under rainfed and irrigated conditions in canola (Brassica
      napus L.).
AB  - Delay of leaf senescence through genetic modification can potentially improve
      crop yield, through maintenance of photosynthetically active leaves for a longer
      period. Plant growth hormones such as cytokinin regulate and delay leaf
      senescence. Here, the structural gene (IPT) encoding the cytokinin biosynthetic
      enzyme isopentenyltransferase was fused to a functionally active fragment of the
      AtMYB32 promoter and was transformed into canola plants. Expression of the
      AtMYB32xs::IPT gene cassette delayed the leaf senescence in transgenic plants
      grown under controlled environment conditions and field experiments conducted for
      a single season at two geographic locations. The transgenic canola plants
      retained higher chlorophyll levels for an extended period and produced
      significantly higher seed yield with similar growth and phenology compared to
      wild type and null control plants under rainfed and irrigated treatments. The
      yield increase in transgenic plants was in the range of 16% to 23% and 7% to 16%
      under rainfed and irrigated conditions, respectively, compared to control plants.
      Most of the seed quality parameters in transgenic plants were similar, and with
      elevated oleic acid content in all transgenic lines and higher oil content and
      lower glucosinolate content in one specific transgenic line as compared to
      control plants. The results suggest that by delaying leaf senescence using the
      AtMYB32xs::IPT technology, productivity in crop plants can be improved under
      water stress and well-watered conditions. 

PMID- 25602961
TI  - Comment on: alpha-smooth muscle actin expression and desmoplastic stromal
      reaction in pancreatic cancer: results from the CONKO-001 study.

PMID- 25602962
TI  - BRCA1 haplotype and clinical benefit of trabectedin in soft-tissue sarcoma
      patients.
AB  - BACKGROUND: This study aimed to determine whether the BRCA1 haplotype was
      associated with trabectedin efficacy in soft-tissue sarcoma (STS) patients.
      METHODS: We analysed BRCA1 single-nucleotide polymorphisms (SNPs) in tumour
      specimens from 135 advanced STS patients enrolled in published phase 2 trials or
      in a compassionate-use programme of trabectedin. Forty-four advanced STS patients
      treated with doxorubicin and 85 patients with localised STS served as controls.
      The 6-month nonprogression rate and overall survival (OS) were analysed according
      to BRCA1 haplotype using log-rank tests. RESULTS: A favourable BRCA1 haplotype
      (presence of at least one AAAG allele) was significantly associated with an
      improved 6-month nonprogression rate. It was the only variable significantly
      associated with OS. No correlations were found between outcomes for patients with
      localised or advanced STS treated with doxorubicin. CONCLUSIONS: The BRCA1
      haplotype represents a potential DNA repair biomarker that can be used for the
      prediction of response to trabectedin in STS patients.

PMID- 25602963
TI  - Impact of investigations in general practice on timeliness of referral for
      patients subsequently diagnosed with cancer: analysis of national primary care
      audit data.
AB  - BACKGROUND: For patients with symptoms of possible cancer who do not fulfil the
      criteria for urgent referral, initial investigation in primary care has been
      advocated in the United Kingdom and supported by additional resources. The
      consequence of this strategy for the timeliness of diagnosis is unknown. METHODS:
      We analysed data from the English National Audit of Cancer Diagnosis in Primary
      Care on patients with lung (1494), colorectal (2111), stomach (246), oesophagus
      (513), pancreas (327), and ovarian (345) cancer relating to the ordering of
      investigations by the General Practitioner and their nature. Presenting symptoms
      were categorised according to National Institute for Health and Care Excellence
      (NICE) guidance on referral for suspected cancer. We used linear regression to
      estimate the mean difference in primary-care interval by cancer, after adjustment
      for age, gender, and the symptomatic presentation category. RESULTS: Primary-care
      investigations were undertaken in 3198/5036 (64%) of cases. The median primary
      care interval was 16 days (IQR 5-45) for patients undergoing investigation and 0
      days (IQR 0-10) for those not investigated. Among patients whose symptoms
      mandated urgent referral to secondary care according to NICE guidelines, between
      37% (oesophagus) and 75% (pancreas) were first investigated in primary care. In
      multivariable linear regression analyses stratified by cancer site, adjustment
      for age, sex, and NICE referral category explained little of the observed
      prolongation associated with investigation. INTERPRETATION: For six specified
      cancers, investigation in primary care was associated with later referral for
      specialist assessment. This effect was independent of the nature of symptoms.
      Some patients for whom urgent referral is mandated by NICE guidance are
      nevertheless investigated before referral. Reducing the intervals between test
      order, test performance, and reporting can help reduce the prolongation of
      primary-care intervals associated with investigation use. Alternative models of
      assessment should be considered.

PMID- 25602964
TI  - Costs of cancer care for use in economic evaluation: a UK analysis of patient
      level routine health system data.
AB  - BACKGROUND: The rising financial burden of cancer on health-care systems
      worldwide has led to the increased demand for evidence-based research on which to
      base reimbursement decisions. Economic evaluations are an integral component of
      this necessary research. Ascertainment of reliable health-care cost and quality
      of-life estimates to inform such studies has historically been challenging, but
      recent advances in informatics in the United Kingdom provide new opportunities.
      METHODS: The costs of hospital care for breast, colorectal and prostate cancer
      disease-free survivors were calculated over 15 months from initial diagnosis of
      cancer using routinely collected data within a UK National Health Service (NHS)
      Hospital Trust. Costs were linked at patient level to patient-reported outcomes
      and registry-derived sociodemographic factors. Predictors of cost and the
      relationship between costs and patient-reported utility were examined. RESULTS:
      The study population included 223 breast cancer patients, 145 colorectal and 104
      prostate cancer patients. The mean 15-month cumulative health-care costs were L12
      595 (95% CI L11 517-L13 722), L12 643 (L11 282-L14 102) and L3722 (L3263-L4208),
      per-patient respectively. The majority of costs occurred within the first 6
      months from diagnosis. Clinical stage was the most important predictor of costs
      for all cancer types. EQ-5D score was predictive of costs in colorectal cancer
      but not in breast or prostate cancer. CONCLUSION: It is now possible to evaluate
      health-care cost using routine NHS data sets. Such methods can be utilised in
      future retrospective and prospective studies to efficiently collect economic
      data.

PMID- 25602965
TI  - ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of
      locally advanced pancreatic cancer.
AB  - BACKGROUND: Several clinical trials have compared chemotherapy alone and
      chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC) treatment.
      However, predictive biomarkers for optimal therapy of LAPC remain to be
      identified.We retrospectively estimated amplification of the ACTN4 gene to
      determine its usefulness as a predictive biomarker for LAPC. METHODS: The copy
      number of ACTN4 in 91 biopsy specimens of LAPC before treatment was evaluated
      using fluorescence in situ hybridisation (FISH). RESULTS: There were no
      statistically significant differences in overall survival (OS) or progression
      free survival (PFS) of LAPC between patients treated with chemotherapy alone or
      with CRT. In a subgroup analysis of patients treated with CRT, patients with a
      copy number increase (CNI) of ACTN4 had a worse prognosis of OS than those with a
      normal copy number (NCN) of ACTN4 (P=0.0005, log-rank test). However, OS in the
      subgroup treated with chemotherapy alone was not significantly different between
      patients with a CNI and a NCN of ACTN4. In the patients with a NCN of ACTN4, the
      median survival time of PFS in CRT-treated patients was longer than that of
      patients treated with chemotherapy alone (P=0.049). CONCLUSIONS: The copy number
      of ACTN4 is a predictive biomarker for CRT of LAPC.

PMID- 25602966
TI  - Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for
      advanced neuroblastoma.
AB  - BACKGROUND: (131)I-metaiodobenzylguanidine (MIBG) is an active
      radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG
      could be combined with vincristine and prolonged irinotecan, although 25% of
      first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG
      with vincristine and 5 days of higher-dose irinotecan. METHODS: Patients 1-30
      years old with advanced neuroblastoma were eligible. Patients received cefixime
      on days -1 to +6, irinotecan (50 mg m(-2) per dose IV) on days 0-4, vincristine
      (2 mg m(-2)) on day 0, MIBG (555 or 666 MBq kg(-1)) on day 1, and peripheral
      blood stem cells on day 13. UGT1A1 genotyping was performed in consenting
      patients. RESULTS: Thirty-two patients (12 phase I ; 20 phase II) received 42
      courses. No dose-limiting toxicities were seen during dose escalation and the
      recommended administered activity was 666 MBq kg(-1). Myelosuppression and
      diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first
      courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80%
      vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of
      32 (28%) patients. CONCLUSIONS: MIBG (666 MBq kg(-1)) with vincristine and this
      irinotecan schedule is tolerable and active, with less severe diarrhoea compared
      with a regimen using more protracted irinotecan.

PMID- 25602968
TI  - Object-based attention underlies the rehearsal of feature binding in visual
      working memory.
AB  - Feature binding is a core concept in many research fields, including the study of
      working memory (WM). Over the past decade, it has been debated whether keeping
      the feature binding in visual WM consumes more visual attention than the
      constituent single features. Previous studies have only explored the contribution
      of domain-general attention or space-based attention in the binding process; no
      study so far has explored the role of object-based attention in retaining binding
      in visual WM. We hypothesized that object-based attention underlay the mechanism
      of rehearsing feature binding in visual WM. Therefore, during the maintenance
      phase of a visual WM task, we inserted a secondary mental rotation (Experiments 1
      3), transparent motion (Experiment 4), or an object-based feature report task
      (Experiment 5) to consume the object-based attention available for binding. In
      line with the prediction of the object-based attention hypothesis, Experiments 1
      5 revealed a more significant impairment for binding than for constituent single
      features. However, this selective binding impairment was not observed when
      inserting a space-based visual search task (Experiment 6). We conclude that
      object-based attention underlies the rehearsal of binding representation in
      visual WM.

PMID- 25602967
TI  - The impact of age on changes in quality of life among breast cancer survivors
      treated with breast-conserving surgery and radiotherapy.
AB  - BACKGROUND: The purpose of the study was to determine the impact of young age on
      health-related quality of life (HRQoL) by comparing HRQoL of younger and older
      breast cancer patients, corrected for confounding, and of young patients and a
      general Dutch population. METHODS: The population consisted of breast cancer
      survivors (stage 0-III) after breast-conserving surgery and radiotherapy. Health
      related quality of life was prospectively assessed using the EORTC QLQ-C30 and
      QLQ-BR23 questionnaires. The association between age (?50; 51-70; ?70 years) and
      HRQoL over time was analysed with mixed modelling. The clinical relevance of
      differences between/within age groups was estimated with Cohen's D and consensus
      based guidelines. The HRQoL data from the young patient cohort were compared with
      Dutch reference data at 3 years after radiotherapy. RESULTS: A total of 1420
      patients completed 3200 questionnaires. Median follow-up was 34 (range 6-70)
      months. Median age was 59 (range 28-85) years. Compared with older subjects,
      young women reported worse HRQoL in the first year after radiotherapy, but
      clinical relevance was limited. Three years after radiotherapy, HRQoL values in
      the younger group were equal to those in the reference population. Pain and
      fatigue after radiotherapy improved, with medium clinical relevance. CONCLUSIONS:
      Three years after radiotherapy for breast cancer, young age was not a risk factor
      for decreased HRQoL.

PMID- 25602969
TI  - Stress affects articulatory planning in reading aloud.
AB  - Three experiments of pseudoword reading assessed whether stress assignment
      affects reading aloud at the level of articulation planning. In Experiment 1
      (immediate reading) both stimulus length (in syllables) and stress type affected
      reading latency and accuracy. Italian pseudowords were named faster and more
      accurately when they were assigned stress on the antepenultimate rather than on
      the penultimate syllable. In Experiment 2 (delayed reading) reading aloud of the
      same stimuli was not affected by length but was still affected by stress type,
      with shorter latencies for pseudowords stressed on the antepenultimate syllable.
      Experiment 3 replicated the results of the first two experiments with new
      materials and with a tightly controlled procedure. These results indicate that
      stress assignment exerts an effect in a processing component where articulation
      is planned since articulation cannot start until stress is assigned. Our results
      also suggest that, in reading aloud, the minimal planning unit for articulation
      is smaller than the whole stimulus, including the first syllable up to the
      stressed unit.

PMID- 25602970
TI  - Super-capacity me! Super-capacity and violations of race independence for self-
      but not for reward-associated stimuli.
AB  - Participants are biased in responding to stimuli associated with themselves
      compared with stimuli related to other people. This self-bias may reflect the
      reward value of self-related stimuli (Sui, He, & Humphreys, 2012). In this
      article, we examined the identification of self- and reward-associated stimuli
      under conditions in which either single or redundant stimuli were presented. The
      redundant stimuli could be the same shape or they could be different shapes both
      associated with either the self or a friend or high or low reward. We formally
      tested whether the redundant stimuli violated the independent race model for the
      identification of multiple stimuli (Miller, 1982) and whether the redundant
      stimuli were processed with super- or limited-capacity (Townsend & Eidels, 2011).
      We found that redundant self stimuli alone both violated the independent race
      model and were processed with super-capacity. In contrast, the redundant high
      reward stimuli did not show race inequality and were associated with limited
      capacity processing. The data advance our theoretical understanding of self bias
      both by demonstrating that it can be distinguished from effects of reward, and by
      suggesting that self-bias can result from the enhanced integration of stimuli
      associated with the self. The implications for understanding self bias effects
      are discussed.

PMID- 25602971
TI  - Exploring HIV prevention strategies among street-based female sex workers in
      Chongqing, China.
AB  - BACKGROUND: Commercial sex plays an increasingly important role in China's
      growing HIV and sexually transmitted infection (STI) epidemics. In China, street
      based sex workers (SSWs) are a subgroup of female sex workers with a particularly
      high risk of HIV/STI infections but are neglected in responses to HIV. This study
      assesses changes in HIV voluntary counseling and testing (VCT) utilization and
      high-risk sexual behaviors following a three-month HIV preventive intervention
      among SSWs in Chongqing, China. METHODS: A three-month intervention was conducted
      by a team of peer educators, outreach workers from community-based organizations
      and health professionals. It mainly included distribution of free pamphlets and
      condoms and delivery of onsite and clinic-based VCT. Cross-sectional surveys were
      conducted prior to (n = 100) and immediately following (n = 112) the intervention
      to assess its impact. In-depth interviews were conducted among 12 SSWs after the
      intervention to further explore potential barriers to HIV prevention. RESULTS:
      The intervention significantly increased SSWs' participation in VCT (from 2.0%
      15.2%, P < 0.001). Despite participants' improved HIV-related knowledge level
      (from 24.0%-73.2%, P < 0.001), there were minimal changes in the levels of condom
      use with clients. Qualitative research revealed that fear of police arrest and
      stigma were the main barriers to VCT utilization. Low condom use was associated
      with family financial constraints, inadequate power in condom negotiation, low
      awareness and misconceptions of HIV infection risks. CONCLUSION: HIV intervention
      improved VCT utilization and knowledge but we did not observe an increase in
      condom use after this short intervention. SSWs faced substantial economic, social
      and environmental barriers to VCT utilization and condom use.

PMID- 25602972
TI  - Prevalence and determinants of mucous membrane irritations in a community near a
      cement factory in Zambia: a cross sectional study.
AB  - Exposure to cement dust has been associated with deleterious health effects in
      humans. This study investigated whether residing near a cement factory increases
      the risk of irritations to the mucous membranes of the eyes and respiratory
      system. A cross sectional study was conducted in Freedom Compound, a community
      bordering a cement factory in Chilanga, Zambia and a control community, Bauleni,
      located 18 km from the cement plant. A modified American Thoracic Society
      questionnaire was administered to 225 and 198 respondents aged 15-59 years from
      Freedom and Bauleni, respectively, to capture symptoms of the irritations.
      Respondents from Freedom Compound, were more likely to experience the
      irritations; adjusted ORs 2.50 (95% CI: 1.65, 3.79), 4.36 (95% CI (2.96, 6.55))
      and 1.94 (95% CI (1.19, 3.18)) for eye, nose and sinus membrane irritations
      respectively. Cohort panel studies to determine associations of cement emissions
      to mucous membrane irritations and respiratory symptoms, coupled with field
      characterization of the exposure are needed to assess whether the excess
      prevalence of symptoms of mucous membrane irritations observed in Freedom
      compound are due to emissions from the cement factory. 

PMID- 25602973
TI  - Determination of total tritium in urine from residents living in the vicinity of
      nuclear power plants in Qinshan, China.
AB  - To estimate the tritium doses of the residents living in the vicinity of a
      nuclear power plant, urine samples of 34 adults were collected from residents
      living near the Qinshan nuclear power plant. The tritium-in-urine (HTO plus OBT)
      was measured by liquid scintillation counting. The doses of tritium-in-urine from
      participants living at 2, 10 and 22 km were in a range of 1.26-6.73 Bq/L, 1.31
      3.09 Bq/L and 2.21-3.81 Bq/L, respectively, while the average activity
      concentrations of participants from the three groups were 3.53 +/- 1.62, 2.09 +/-
      0.62 and 2.97 +/- 0.78 Bq/L, respectively. The personal committed effective doses
      for males were 2.5 +/- 1.7 nSv and for females they were 2.9 +/- 1.3 nSv. These
      results indicate that tritium concentrations in urine samples from residents
      living at 2 km from a nuclear power plant are significantly higher than those at
      10 km. It may be the downwind direction that caused a higher dose in participants
      living at 22 km. All the measured doses of tritium-in-urine are in a background
      level range. 

PMID- 25602974
TI  - BF3-Et2O mediated skeletal rearrangements of norbornyl appended
      cyclopentanediols.
AB  - An unusual cascade rearrangement has been noticed as a competitive reaction
      during the treatment of norbornyl appended cyclopentanediols with a Lewis acid
      (LA): a BF3-Et2O mediated pinacol-pinacolone rearrangement. Deketalization and
      pinacolone rearrangement occur at two different sites in the molecule and are
      responsible for the observed cascade rearrangement product. However,
      deketalization appears to be triggering the cascade steps. The kinetically more
      stable pinacolone product with an exo-Me group was observed in the case of the
      bromo analogue, whereas, the thermodynamically more stable pinacolone product
      with an endo-Me group was observed in the case of the chloro analogue.
      Epimerization via tautomerization of one diastereomer to the other diastereomer
      under Lewis acid reflux conditions is possible. On the contrary, the diol
      equivalent epoxides provide only the diastereomeric mixture of pinacolone
      products under similar LA reaction conditions. The lower yields observed in the
      case of the epoxides are due to unwanted side reactions taking place between the
      two competitive reactive centers, namely, ketal and epoxide. Further, a sequence
      of elimination, nucleophilic substitution and Ritter type hydrolysis reactions of
      the epoxides resulted in unexpected elimination products. This transformation not
      only facilitates a regioselective epoxide opening, but also provides a new route
      for the preparation of allylic amides of the norbornyl appended cyclopentane ring
      system. 

PMID- 25602975
TI  - Nanofibrous adhesion: the twin of gecko adhesion.
AB  - Inspired by dusty spider dragline silk, we studied the adhesive interaction
      between artificial nanofibers and their aerosol surroundings. The nanofibers are
      found to be able to actively capture particulate matters from the environment,
      exactly as the spider dragline silk does. Examinations prove that such
      nanofibrous adhesion is insensitive to the chemical nature of the fibers and the
      physical states of the particulate matter and depends only on the fiber
      diameters. Such facts indicate that nanofibrous adhesion is a case of dry
      adhesion, mainly governed by van der Waals force, sharing the same mechanism to
      gecko adhesion. Nanofibrous adhesion is of great importance and has promising
      potential. For instance, in this work, nanofibers are fabricated into a thin and
      translucent filter, which has a filtration performance, as high as 95%, that
      easily outperformed ordinary ones. We believe that this adhesive property of
      nanofibers will open up broader applications in both scientific and industrial
      fields. 

PMID- 25602976
TI  - Parental expectations of maternal and child health services.
AB  - This article reports on survey research (N = 1,418) aimed at examining whether
      parental expectations of maternal and child health (MCH) services are influenced
      by group characteristics (e.g., socioeconomic status [SES], ethnicity, at risk of
      poverty) and/or individual parenting context variables (e.g., received social
      support) in a context where these services are available to all. The findings
      reveal that parents have different expectations about the technical and
      relational expertise of MCH nurses. However, the authors found only very weak
      associations between family characteristics and parental expectations, suggesting
      that individual differences matter more than SES and other more traditional
      distinctions. Implications for MCH services are made.

PMID- 25602977
TI  - Prenylated benzophenones from Triadenum japonicum.
AB  - Six new prenylated benzophenones, (-)-nemorosonol (1) and trijapins A-E (2-6),
      were isolated from the aerial parts of Triadenum japonicum. (-)-Nemorosonol (1)
      and trijapins A-C (2-4) have a common tricyclo[4.3.1.0(3,7)]decane skeleton,
      while 1 is an enantiomer of (+)-nemorosonol previously isolated from Clusia
      nemorosa. The absolute configuration of (-)-nemorosonol (1) was assigned by ECD
      spectroscopy. Trijapins A-C (2-4) are analogues of 1 possessing an additional
      tetrahydrofuran ring. Trijapins D (5) and E (6) are prenylated benzophenones with
      a 1,2-dioxane moiety and a hydroperoxy group, respectively. (-)-Nemorosonol (1)
      exhibited antimicrobial activity against Escherichia coli (MIC, 8 MUg/mL),
      Staphylococcus aureus (MIC, 16 MUg/mL), Bacillus subtilis (MIC, 16 MUg/mL),
      Micrococcus luteus (MIC, 32 MUg/mL), Aspergillus niger (IC50, 16 MUg/mL),
      Trichophyton mentagrophytes (IC50, 8 MUg/mL), and Candida albicans (IC50, 32
      MUg/mL), while trijapin D (5) showed antimicrobial activity against C. albicans
      (IC50, 8 MUg/mL). 

PMID- 25602978
TI  - Taxes and subsidies to improve diet--reply.

PMID- 25602982
TI  - L'escalier canadien: Kathleen Daly.

PMID- 25602983
TI  - End-of-Life medications draw more attention, greater scrutiny.

PMID- 25602984
TI  - A new federal health care strategy.

PMID- 25602990
TI  - Improving long-term psychiatric care: bring back the asylum.

PMID- 25602991
TI  - Navigating the rise of high-deductible health insurance: childbirth in the bronze
      age.

PMID- 25602992
TI  - Legislative prescriptions for controlling nonmedical vaccine exemptions.

PMID- 25602993
TI  - A piece of my mind. Flamed on the Net.

PMID- 25602994
TI  - Hematopoietic stem cell transplantation for MS: extraordinary evidence still
      needed.

PMID- 25602996
TI  - Trends in use of and reproductive outcomes associated with intracytoplasmic sperm
      injection.
AB  - IMPORTANCE: Intracytoplasmic sperm injection (ICSI) is increasingly used in
      patients without severe male factor infertility without clear evidence of a
      benefit over conventional in vitro fertilization (IVF). OBJECTIVE: To assess
      national trends and reproductive outcomes for fresh IVF cycles (embryos
      transferred without being frozen) following the use of ICSI compared with
      conventional IVF with respect to clinical indications for ICSI use. DESIGN,
      SETTING, AND POPULATION: Retrospective cohort study using data on fresh IVF and
      ICSI cycles reported to the US National Assisted Reproductive Technology
      Surveillance System during 1996-2012. MAIN OUTCOMES AND MEASURES: Trends in ICSI
      use during 1996-2012 with respect to male factor infertility, unexplained
      infertility, maternal age 38 years or older, low oocyte yield, and 2 or more
      prior assisted reproductive technology cycles; reproductive outcomes for
      conventional IVF and ICSI cycles during 2008-2012, stratified by the presence or
      absence of male factor infertility. RESULTS: Of the 1,395,634 fresh IVF cycles
      from 1996 through 2012, 908,767 (65.1%) used ICSI and 499,135 (35.8%) reported
      male factor infertility. Among cycles with male factor infertility, ICSI use
      increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506) (P < .001) during
      1996-2012; for those without male factor infertility, ICSI use increased from
      15.4% (4197/27,191) to 66.9% (42,321/63,250) (P < .001). During 2008-2012, male
      factor infertility was reported for 35.7% (176,911/494,907) of fresh cycles.
      Among those cycles, ICSI use was associated with a lower multiple birth rate
      compared with conventional IVF (30.9% vs 34.2%; adjusted relative risk [RR],
      0.87; 95% CI, 0.83-0.91). Among cycles without male factor infertility (n =
      317,996), ICSI use was associated with lower rates of implantation (23.0% vs
      25.2%; adjusted RR, 0.93; 95% CI, 0.91-0.95), live birth (36.5% vs 39.2%;
      adjusted RR, 0.95; 95% CI, 0.93-0.97), and multiple live birth (30.1% vs 31.0%;
      adjusted RR, 0.93; 95% CI, 0.91-0.95) vs conventional IVF. CONCLUSIONS AND
      RELEVANCE: Among fresh IVF cycles in the United States, ICSI use increased from
      36.4% in 1996 to 76.2% in 2012, with the largest relative increase among cycles
      without male factor infertility. Compared with conventional IVF, ICSI use was not
      associated with improved postfertilization reproductive outcomes, irrespective of
      male factor infertility diagnosis.

PMID- 25602998
TI  - Association of nonmyeloablative hematopoietic stem cell transplantation with
      neurological disability in patients with relapsing-remitting multiple sclerosis.
AB  - IMPORTANCE: No current therapy for relapsing-remitting multiple sclerosis (MS)
      results in significant reversal of disability. OBJECTIVE: To determine the
      association of nonmyeloablative hematopoietic stem cell transplantation with
      neurological disability and other clinical outcomes in patients with MS. DESIGN,
      SETTING, AND PARTICIPANTS: Case series of patients with relapsing-remitting MS (n
      = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60
      years; 85 women) treated at a single US institution between 2003 and 2014 and
      followed up for 5 years. Final follow-up was completed in June 2014.
      INTERVENTIONS: Treatment with cyclophosphamide and alemtuzumab (22 patients) or
      cyclophosphamide and thymoglobulin (129 patients) followed by infusion of
      unmanipulated peripheral blood stem cells. MAIN OUTCOMES AND MEASURES: Primary
      end point was reversal or progression of disability measured by change in the
      Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0
      10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS)
      score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional
      Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and
      T2 lesion volume on brain magnetic resonance imaging scan. RESULTS: Outcome
      analysis was available for 145 patients with a median follow-up of 2 years and a
      mean of 2.5 years. Scores from the EDSS improved significantly from a
      pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n =
      82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each
      assessment). There was significant improvement in disability (decrease in EDSS
      score of >=1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23
      patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival
      was 80% and progression-free survival was 87%. The NRS scores improved
      significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n =
      78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at
      each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2
      years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of
      life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64
      (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P <
      .001). There was a decrease in T2 lesion volume from a pretransplant median of
      8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001)
      at the last posttransplant assessment (mean follow-up, 27 months; n = 128).
      CONCLUSIONS AND RELEVANCE: Among patients with relapsing-remitting MS,
      nonmyeloablative hematopoietic stem cell transplantation was associated with
      improvement in neurological disability and other clinical outcomes. These
      preliminary findings from this uncontrolled study require confirmation in
      randomized trials.

PMID- 25602997
TI  - Association between hospitalization for pneumonia and subsequent risk of
      cardiovascular disease.
AB  - IMPORTANCE: The risk of cardiovascular disease (CVD) after infection is poorly
      understood. OBJECTIVE: To determine whether hospitalization for pneumonia is
      associated with an increased short-term and long-term risk of CVD. DESIGN,
      SETTINGS, AND PARTICIPANTS: We examined 2 community-based cohorts: the
      Cardiovascular Health Study (CHS, n = 5888; enrollment age, >=65 years;
      enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study
      (ARIC, n = 15,792; enrollment age, 45-64 years; enrollment period, 1987-1989).
      Participants were followed up through December 31, 2010. We matched each
      participant hospitalized with pneumonia to 2 controls. Pneumonia cases and
      controls were followed for occurrence of CVD over 10 years after matching. We
      estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for
      demographics, CVD risk factors, subclinical CVD, comorbidities, and functional
      status. EXPOSURES: Hospitalization for pneumonia. MAIN OUTCOMES AND MEASURES:
      Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease).
      RESULTS: Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after
      pneumonia hospitalization. CVD risk after pneumonia was highest in the first
      year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95%
      CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI,
      2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10;
      95% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year,
      when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18-2.55). In
      ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization.
      CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI,
      1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23
      3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20
      3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10
      2.66). After the second year, the HRs were no longer statistically significant.
      CONCLUSIONS AND RELEVANCE: Hospitalization for pneumonia was associated with
      increased short-term and long-term risk of CVD, suggesting that pneumonia may be
      a risk factor for CVD.

PMID- 25602999
TI  - Resective epilepsy surgery for drug-resistant focal epilepsy: a review.
AB  - IMPORTANCE: Epilepsy surgery is indicated for patients with focal seizures who do
      not respond to appropriate antiepileptic drug therapy consisting of 2 or more
      medications. OBJECTIVES: To review resective surgery outcomes for focal epilepsy,
      to identify which patients benefit the most, and to discuss why epilepsy surgery
      may not be universally accepted. EVIDENCE REVIEW: Medline and Cochrane databases
      were searched between January 1993 and June 2014 for randomized clinical trials,
      meta-analyses, systematic reviews, and large retrospective case series (>300
      patients) using Medical Subject Headings and indexed text terms. Fifty-five
      articles were included. Subpopulations and prognostic factors were identified.
      Systematic reviews for cognitive, psychiatric, quality-of-life, and psychosocial
      outcomes were included. FINDINGS: Two randomized clinical trials enrolling 118
      patients with temporal lobe epilepsy found greater freedom from seizures with
      surgery when compared with continued medical treatment (58% vs 8% [n = 80] and
      73% vs 0% [n = 38], P < .001). Nine systematic reviews and 2 large case series of
      medically refractory patients treated with surgery reported seizure-free outcomes
      in 34% to 74% of patients (median, 62.4%). The remainder of systematic reviews
      and meta-analyses examined subpopulations. Epilepsy surgery was less effective
      when there were extratemporal lesions, the epilepsy was not associated with a
      structural lesion, or both. Seizure-free outcomes were similar between children
      and adults. Hippocampal sclerosis and benign tumors were associated with better
      outcomes relative to other pathologies. Similar procedures such as selective
      amygdalohippocampectomy and temporal lobectomy for temporal lobe epilepsy were
      associated with subtle differences in seizure and neuropsychological outcome.
      There is low perioperative mortality (0.1%-0.5%) from epilepsy surgery. The most
      frequent neurologic complication is visual field defect occurring from temporal
      lobe resection. Quality of life improved after surgery but improved the most in
      patients who were seizure-free after surgery. CONCLUSIONS AND RELEVANCE: Epilepsy
      surgery reduced seizure activity in randomized clinical trials when compared with
      continued medical therapy. Long-term cognitive, psychiatric, psychosocial, and
      quality-of-life outcomes were less well defined. Despite good outcomes from high
      quality clinical trials, referrals of patients with seizures refractory to
      medical treatment remain infrequent.

PMID- 25603000
TI  - Antibiotics for acute otitis media: yes or no.

PMID- 25603001
TI  - An overview of treatments for endometriosis.
AB  - CLINICAL QUESTION: What treatments are associated with improved outcomes for
      women with endometriosis? BOTTOM LINE: The levonorgestrel-releasing intrauterine
      system (LNG-IUD), gonadotropin-releasing hormone analogues (GnRHa; nafarelin,
      leuprolide, buserelin, goserelin, triptorelin), laparoscopic ablation, and
      excision are associated with relief of pain due to endometriosis. Gonadotropin
      releasing hormone analogues and laparoscopic ablation or excision are associated
      with increased clinical pregnancy rates in women with endometriosis. Gonadotropin
      releasing hormone analogues, danazol, and depot progestagens are associated with
      a higher incidence of adverse events.

PMID- 25603002
TI  - A crusted rash in a patient with AIDS.

PMID- 25603003
TI  - Diagnostic performance by medical students working individually or in teams.

PMID- 25603004
TI  - Long-acting beta-agonists with vs without inhaled corticosteroids for COPD.

PMID- 25603005
TI  - Long-acting beta-agonists with vs without inhaled corticosteroids for COPD-
      reply.

PMID- 25603006
TI  - Antenatal magnesium sulfate and outcomes for school-aged children.

PMID- 25603007
TI  - Antenatal magnesium sulfate and outcomes for school-aged children--reply.

PMID- 25603008
TI  - Taxes and subsidies to improve diet.

PMID- 25603010
TI  - Columbus and Vesalius--the age of discoverers.

PMID- 25603011
TI  - JAMA patient page. Treatments for infertility.

PMID- 25603013
TI  - Recovery narrative photovoice: Feasibility of a writing and photography
      intervention for serious mental illnesses.
AB  - OBJECTIVE: The primary purpose of this article is to describe the development and
      feasibility of the Recovery Narrative Photovoice intervention. The nature of this
      intervention will be discussed, including facilitating empowerment and a positive
      sense of identity among people with serious mental illnesses. We will also
      describe the integration of Photovoice methodology with psychoeducational
      components, informed by principles of the recovery movement and narrative
      therapy. METHODS: Sixteen participants with serious mental illnesses from a
      psychosocial rehabilitation and education center in the Northeast participated in
      a pilot study evaluating this new 10-week intervention with a pre-post test
      design. To assess feasibility, descriptive statistical analyses were conducted of
      attendance data and number of works produced. The pilot study was implemented in
      2 consecutive waves with 8 participants each. RESULTS: High rates of attendance
      (69%) and production of photovoice works (82%) were demonstrated over the course
      of the 2 waves of the pilot. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings
      support the feasibility and acceptability of the Recovery Narrative Photovoice
      for individuals with serious mental illnesses. These results reflect the
      potential for using this intervention in psychiatric rehabilitation settings to
      facilitate recovery-related outcomes, including empowerment, positive identity,
      and community integration. Future research will require a replication of pre-post
      assessment of this intervention to further establish the efficacy of this
      program.

PMID- 25603012
TI  - Near-Infrared Spectroscopy in the Monitoring of Adult Traumatic Brain Injury: A
      Review.
AB  - Cerebral near-infrared spectroscopy (NIRS) has long represented an exciting
      prospect for the noninvasive monitoring of cerebral tissue oxygenation and
      perfusion in the context of traumatic brain injury (TBI), although uncertainty
      still exists regarding the reliability of this technology specifically within
      this field. We have undertaken a review of the existing literature relating to
      the application of NIRS within TBI. We discuss current "state-of-the-art" NIRS
      monitoring, provide a brief background of the technology, and discuss the
      evidence regarding the ability of NIRS to substitute for established invasive
      monitoring in TBI. 

PMID- 25603014
TI  - Cheese and Cardiovascular Disease Risk: A Review of the Evidence and Discussion
      of Possible Mechanisms.
AB  - Currently, the effect of dairy products on cardiovascular risk is a topic much
      debated and with conflicting results. The purpose of this review is to give an
      overview of the existing literature regarding the effect of cheese intake and
      risk of cardiovascular disease (CVD). Studies included reporting the intake of
      cheese and risk of CVD or risk markers of CVD represent four human intervention
      studies, nine prospective studies, one prospective case-cohort study, one
      prospective nested case-control study, five case-control studies, five cross
      sectional studies and three correlation studies. The possible mechanisms that may
      be of importance include calcium, protein, fermentation and the fatty acid
      composition of cheese. Results from four prospective studies reported no
      association between cheese intake and CVD risk, whereas one reported an increased
      risk, two reported a decreased risk and one reported no association in men but a
      decreased risk in women. In addition, results from four intervention studies
      indicated no harmful effect on cholesterol concentrations when comparing fat
      intake from cheese with fat from butter. The underlying mechanisms for these
      findings still need to be elucidated. 

PMID- 25603017
TI  - Silicon-tethered strategy for copper(I)-catalyzed stereo- and regioselective
      alkylboration of alkynes.
AB  - Stereoselective silicon-tethered alkylboration of alkynes in the presence of a
      copper(I) catalyst and a diboron reagent provided the corresponding cyclic
      alkenylboronates in high yields (up to 99% yield) with excellent regio- and syn
      selectivities (E/Z = <1:99). The products, which can be considered as the formal
      alkyne intermolecular alkylboration products, undergo subsequent selective
      derivatization, including ring opening, to give functionalized trans-stilbene
      derivatives. 

PMID- 25603016
TI  - Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and
      progenitor cells.
AB  - Hematologic toxicity is a major cause of mortality in radiation emergency
      scenarios and a primary side effect concern in patients undergoing chemo
      radiotherapy. Therefore, there is a critical need for the development of novel
      and more effective approaches to manage this side effect. Catalase is a potent
      antioxidant enzyme that coverts hydrogen peroxide into hydrogen and water. In
      this study, we evaluated the efficacy of catalase as a protectant against
      ionizing radiation (IR)-induced toxicity in hematopoietic stem and progenitor
      cells (HSPCs). The results revealed that catalase treatment markedly inhibits IR
      induced apoptosis in murine hematopoietic stem cells and hematopoietic progenitor
      cells. Subsequent colony-forming cell and cobble-stone area-forming cell assays
      showed that catalase-treated HSPCs can not only survive irradiation-induced
      apoptosis but also have higher clonogenic capacity, compared with vehicle-treated
      cells. Moreover, transplantation of catalase-treated irradiated HSPCs results in
      high levels of multi-lineage and long-term engraftments, whereas vehicle-treated
      irradiated HSPCs exhibit very limited hematopoiesis reconstituting capacity.
      Mechanistically, catalase treatment attenuates IR-induced DNA double-strand
      breaks and inhibits reactive oxygen species. Unexpectedly, we found that the
      radioprotective effect of catalase is associated with activation of the signal
      transducer and activator of transcription 3 (STAT3) signaling pathway and
      pharmacological inhibition of STAT3 abolishes the protective activity of
      catalase, suggesting that catalase may protect HSPCs against IR-induced toxicity
      via promoting STAT3 activation. Collectively, these results demonstrate a
      previously unrecognized mechanism by which catalase inhibits IR-induced DNA
      damage and apoptosis in HSPCs. 

PMID- 25603020
TI  - Silibinin affects tumor cell growth because of reduction of stemness properties
      and induction of apoptosis in 2D and 3D models of MDA-MB-468.
AB  - Silibinin, with a strong antioxidant activity and a weak cytotoxic property, is
      considered a candidate for cancer prevention. As there is no information on its
      effect on breast cancer tumor-initiating cells [cancer stem cells (CSCs)] in a 3D
      culture model, which more closely mimic natural tissues, we carried out this
      study to determine whether silibinin can target breast CSCs in MDA-MB-468 cells
      cultured under 3D and 2D conditions. Silibinin was added to culture medium of MDA
      MB-468 at a half maximal inhibitory concentration (IC50) dose in 2D and 3D
      models. Then, stemness properties were assessed using colony and sphere-formation
      tests. Flow cytometry and real-time PCR were used to determine the different
      expression levels of stem cell-related marker at protein and mRNA levels under
      both culture conditions. Our results showed that silibinin inhibits cell growth
      in a dose-dependent manner by induction of apoptosis, alteration of the cell
      cycle, reduction of stemness properties and function, and induction of tumoral
      differentiation. The mechanism of silibinin action and also the response of tumor
      cells differed when cells were cultured in a 3D model compared with a 2D model.
      Silibinin may potentially target breast CSCs. Moreover, tumor-initiating cells
      are more sensitive to silibinin in a 3D culture than in a 2D culture. 

PMID- 25603021
TI  - Silymarin and hepatocellular carcinoma: a systematic, comprehensive, and critical
      review.
AB  - The blessed milk thistle (Silybum marianum L.), a flowering plant native to
      Mediterranean Europe, has been consumed and extensively used as a cure for
      various chronic liver ailments over several centuries. Milk thistle extract,
      known as silymarin, is a complex mixture of seven major flavonolignans and one
      flavonoid. The phytoconstituents of silymarin owe their therapeutic and
      hepatoprotective effects to their strong antioxidant and anti-inflammatory
      properties. Primary liver cancer, also known as hepatocellular carcinoma (HCC),
      occurs in a milieu of oxidative stress and inflammation. The etiology of HCC
      includes chronic infection with hepatitis B and C viruses, cirrhosis, and
      exposure to dietary and environmental hepatocarcinogens. Current therapeutic
      options for HCC, including surgical resection and liver transplantation, have
      limited benefits and are essentially ineffective. Chemoprevention, using
      phytochemicals with potent antioxidant and anti-inflammatory properties,
      represents a fascinating strategy, which has been a subject of intense
      investigation in the recent years. In this review, we explore the potential role
      of silymarin as a chemopreventive and therapeutic agent for HCC. The review
      systematically evaluates the preclinical in-vitro and in-vivo studies
      investigating the effects of silymarin and its constituents on HCC. The
      biochemical mechanisms involved in the anti-liver-cancer effects of silymarin
      have been presented. The current status of clinical studies evaluating the
      potential of role of silymarin in liver cancer, especially that caused by
      hepatitis C virus, has also been examined. Potential challenges and future
      directions of research involved in the 'bench-to-bedside' transition of silymarin
      phytoconstituents for the chemoprevention and treatment of HCC have also been
      discussed. 

PMID- 25603022
TI  - Pulsatile arterial wall-blood flow interaction with wall pre-stress computed
      using an inverse algorithm.
AB  - BACKGROUND: The computation of arterial wall deformation and stresses under
      physiologic conditions requires a coupled compliant arterial wall-blood flow
      interaction model. The in-vivo arterial wall motion is constrained by tethering
      from the surrounding tissues. This tethering, together with the average in-vivo
      pressure, results in wall pre-stress. For an accurate simulation of the
      physiologic conditions, it is important to incorporate the wall pre-stress in the
      computational model. The computation of wall pre-stress is complex, as the un
      loaded and un-tethered arterial shape with residual stress is unknown. In this
      study, the arterial wall deformation and stresses in a canine femoral artery
      under pulsatile pressure was computed after incorporating the wall pre-stresses.
      A nonlinear least square optimization based inverse algorithm was developed to
      compute the in-vivo wall pre-stress. METHODS: First, the proposed inverse
      algorithm was used to obtain the un-loaded and un-tethered arterial geometry from
      the unstressed in-vivo geometry. Then, the un-loaded, and un-tethered arterial
      geometry was pre-stressed by applying a mean in-vivo pressure of 104.5 mmHg and
      an axial stretch of 48% from the un-tethered length. Finally, the physiologic
      pressure pulse was applied at the inlet and the outlet of the pre-stressed
      configuration to calculate the in-vivo deformation and stresses. The wall
      material properties were modeled with an incompressible, Mooney-Rivlin model
      derived from previously published experimental stress-strain data (Attinger et
      al., 1968). RESULTS: The un-loaded and un-tethered artery geometry computed by
      the inverse algorithm had a length, inner diameter and thickness of 35.14 mm,
      3.10 mm and 0.435 mm, respectively. The pre-stressed arterial wall geometry was
      obtained by applying the in-vivo axial-stretch and average in-vivo pressure to
      the un-loaded and un-tethered geometry. The length of the pre-stressed artery,
      51.99 mm, was within 0.01 mm (0.019%) of the in-vivo length of 52.0 mm; the inner
      diameter of 3.603 mm was within 0.003 mm (0.08%) of the corresponding in-vivo
      diameter of 3.6 mm, and the thickness of 0.269 mm was within 0.0015 mm (0.55%) of
      the in-vivo thickness of 0.27 mm. Under physiologic pulsatile pressure applied to
      the pre-stressed artery, the time averaged longitudinal stress was found to be
      42.5% higher than the circumferential stresses. The results of this study are
      similar to the results reported by Zhang et al., (2005) for the left anterior
      descending coronary artery. CONCLUSIONS: An inverse method was adopted to compute
      physiologic pre-stress in the arterial wall before conducting pulsatile
      hemodynamic calculations. The wall stresses were higher in magnitude in the
      longitudinal direction, under physiologic pressure after incorporating the effect
      of in-vivo axial stretch and pressure loading.

PMID- 25603023
TI  - Fast learning of simple perceptual discriminations reduces brain activation in
      working memory and in high-level auditory regions.
AB  - Introducing simple stimulus regularities facilitates learning of both simple and
      complex tasks. This facilitation may reflect an implicit change in the strategies
      used to solve the task when successful predictions regarding incoming stimuli can
      be formed. We studied the modifications in brain activity associated with fast
      perceptual learning based on regularity detection. We administered a two-tone
      frequency discrimination task and measured brain activation (fMRI) under two
      conditions: with and without a repeated reference tone. Although participants
      could not explicitly tell the difference between these two conditions, the
      introduced regularity affected both performance and the pattern of brain
      activation. The "No-Reference" condition induced a larger activation in
      frontoparietal areas known to be part of the working memory network. However,
      only the condition with a reference showed fast learning, which was accompanied
      by a reduction of activity in two regions: the left intraparietal area, involved
      in stimulus retention, and the posterior superior-temporal area, involved in
      representing auditory regularities. We propose that this joint reduction reflects
      a reduction in the need for online storage of the compared tones. We further
      suggest that this change reflects an implicit strategic shift "backwards" from
      reliance mainly on working memory networks in the "No-Reference" condition to
      increased reliance on detected regularities stored in high-level auditory
      networks.

PMID- 25603024
TI  - How Early Does the Brain Distinguish between Regular Words, Irregular Words, and
      Pseudowords during the Reading Process? Evidence from Neurochronometric TMS.
AB  - Cognitive theories on reading propose that the characteristics of written stimuli
      determine how they are processed in the brain. However, whether the brain
      distinguishes between regular words, irregular words, and pseudowords already at
      an early stage of the reading process is still subject to debate. Here we used
      chronometric TMS to address this issue. During the first 140 msec of regular
      word, irregular word, and pseudoword reading, TMS was used to disrupt the
      function of the ventral occipitotemporal, posterior middle temporal, and
      supramarginal gyri, which are key areas involved in orthographic, semantic, and
      phonological processing, respectively. Early TMS stimulation delivered on
      posterior middle temporal and supramarginal gyri affected regular and irregular
      word, but not pseudoword, reading. In contrast, ventral occipitotemporal
      disruption affected both word and pseudoword reading. We thus found evidence for
      an early distinction between word and pseudoword processing in the semantic and
      phonological systems, but not in the orthographic system. 

PMID- 25603025
TI  - Neural reorganization and compensation in aging.
AB  - According to prominent theories of aging, the brain may reorganize to compensate
      for neural deterioration and prevent or offset cognitive decline. A frequent and
      striking finding in functional imaging studies is that older adults recruit
      additional regions relative to young adults performing the same task. This is
      often interpreted as evidence for functional reorganization, suggesting that, as
      people age, different regions or networks may support the same cognitive
      functions. Associations between additional recruitment and better performance in
      older adults have led to the suggestion that the additional recruitment may
      contribute to preserved cognitive function in old age and may explain some of the
      variation among individuals in preservation of function. However, many
      alternative explanations are possible, and recent findings and methodological
      developments have highlighted the need for more systematic approaches to
      determine whether reorganization occurs with age and whether it benefits
      performance. We reevaluate current evidence for compensatory functional
      reorganization in the light of recent moves to address these challenges.

PMID- 25603026
TI  - Metacognitive processes in executive control development: the case of reactive
      and proactive control.
AB  - Young children engage cognitive control reactively in response to events, rather
      than proactively preparing for events. Such limitations in executive control have
      been explained in terms of fundamental constraints on children's cognitive
      capacities. Alternatively, young children might be capable of proactive control
      but differ from older children in their metacognitive decisions regarding when to
      engage proactive control. We examined these possibilities in three conditions of
      a task-switching paradigm, varying in whether task cues were available before or
      after target onset. RTs, ERPs, and pupil dilation showed that 5-year-olds did
      engage in advance preparation, a critical aspect of proactive control, but only
      when reactive control was made more difficult, whereas 10-year-olds engaged in
      proactive control whenever possible. These findings highlight metacognitive
      processes in children's cognitive control, an understudied aspect of executive
      control development. 

PMID- 25603028
TI  - Rescaling retinal size into perceived size: evidence for an occipital and
      parietal bottleneck.
AB  - The spatial and temporal context of an object influence its perceived size. Two
      visual illusions illustrate this nicely: the size adaptation effect and the
      Ebbinghaus illusion. Whereas size adaptation affects size rescaling of a target
      circle via a previously presented, differently sized adaptor circle, the
      Ebbinghaus illusion alters perceived size by virtue of surrounding circles. In
      the classical Ebbinghaus setting, the surrounding circles are shown
      simultaneously with the target. However, size underestimation persists when the
      surrounding circles precede the target. Such a temporal separation of inducer and
      target circles in both illusions permits the comparison of BOLD signals elicited
      by two displays that, although objectively identical, elicit different percepts.
      The current study combined both illusions in a factorial design to identify a
      presumed common central mechanism involved in rescaling retinal into perceived
      size. At the behavioral level, combining both illusions did not affect perceived
      size further. At the neural level, however, this combination induced functional
      activation beyond that induced by either illusion separately: An underadditive
      activation pattern was found within left lingual gyrus, right supramarginal
      gyrus, and right superior parietal cortex. These findings provide direct
      behavioral and functional evidence for the presence of a neural bottleneck in
      rescaling retinal into perceived size, a process vital for visual perception.

PMID- 25603027
TI  - The default mode of human brain function primes the intentional stance.
AB  - Humans readily adopt an intentional stance to other people, comprehending their
      behavior as guided by unobservable mental states such as belief, desire, and
      intention. We used fMRI in healthy adults to test the hypothesis that this stance
      is primed by the default mode of human brain function present when the mind is at
      rest. We report three findings that support this hypothesis. First, brain regions
      activated by actively adopting an intentional rather than nonintentional stance
      to a social stimulus were anatomically similar to those demonstrating default
      responses to fixation baseline in the same task. Second, moment-to-moment
      variation in default activity during fixation in the dorsomedial PFC was related
      to the ease with which participants applied an intentional--but not
      nonintentional--stance to a social stimulus presented moments later. Finally,
      individuals who showed stronger dorsomedial PFC activity at baseline in a
      separate task were generally more efficient when adopting the intentional stance
      and reported having greater social skills. These results identify a biological
      basis for the human tendency to adopt the intentional stance. More broadly, they
      suggest that the brain's default mode of function may have evolved, in part, as a
      response to life in a social world.

PMID- 25603029
TI  - Rhythmic gamma stimulation affects bistable perception.
AB  - When our brain is confronted with ambiguous visual stimuli, perception
      spontaneously alternates between different possible interpretations although the
      physical stimulus remains the same. Both alpha (8-12 Hz) and gamma (>30 Hz)
      oscillations have been reported to correlate with such spontaneous perceptual
      reversals. However, whether these oscillations play a causal role in triggering
      perceptual switches remains unknown. To address this question, we applied
      transcranial alternating current stimulation (tACS) over the posterior cortex of
      healthy human participants to boost alpha and gamma oscillations. At the same
      time, participants were reporting their percepts of an ambiguous structure-from
      motion stimulus. We found that tACS in the gamma band (60 Hz) increased the
      number of spontaneous perceptual reversals, whereas no significant effect was
      found for tACS in alpha (10 Hz) and higher gamma (80 Hz) frequencies. Our results
      suggest a mechanistic role of gamma but not alpha oscillations in the resolution
      of perceptual ambiguity.

PMID- 25603030
TI  - Flexible information coding in human auditory cortex during perception, imagery,
      and STM of complex sounds.
AB  - Auditory cortex is the first cortical region of the human brain to process
      sounds. However, it has recently been shown that its neurons also fire in the
      absence of direct sensory input, during memory maintenance and imagery. This has
      commonly been taken to reflect neural coding of the same acoustic information as
      during the perception of sound. However, the results of the current study suggest
      that the type of information encoded in auditory cortex is highly flexible.
      During perception and memory maintenance, neural activity patterns are stimulus
      specific, reflecting individual sound properties. Auditory imagery of the same
      sounds evokes similar overall activity in auditory cortex as perception. However,
      during imagery abstracted, categorical information is encoded in the neural
      patterns, particularly when individuals are experiencing more vivid imagery. This
      highlights the necessity to move beyond traditional "brain mapping" inference in
      human neuroimaging, which assumes common regional activation implies similar
      mental representations.

PMID- 25603031
TI  - Generation of Bayesian prediction models for OATP-mediated drug-drug interactions
      based on inhibition screen of OATP1B1, OATP1B1*15 and OATP1B3.
AB  - Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are
      important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated
      drug-drug interactions (DDIs) is therefore important for successful drug
      development. A promising approach for early screening and prediction of DDIs is
      computational modeling. In this study we aimed to generate a rapid, single
      Bayesian prediction model for OATP1B1, OATP1B1*15 and OATP1B3 inhibition. Besides
      our previously generated HEK-OATP1B1 and HEK-OATP1B1*15 cells, we now generated
      and characterized HEK-OATP1B3 cells. Using these cell lines we investigated the
      inhibitory potential of 640 FDA-approved drugs from a commercial library (10MUM)
      on the uptake of [(3)H]-estradiol-17beta-d-glucuronide (1MUM) by OATP1B1,
      OATP1B1*15, and OATP1B3. Using a cut-off of ?60% inhibition, 8% and 7% of the 640
      drugs were potent OATP1B1 and OATP1B1*15 inhibitors, respectively. Only 1% of the
      tested drugs significantly inhibited OATP1B3, which was not sufficient for
      Bayesian modeling. Modeling of OATP1B1 and OATP1B1*15 inhibition revealed that
      presence of conjugated systems and (hetero)cycles with acceptor/donor atoms in-
      or outside the ring enhance the probability of a molecule binding these
      transporters. The overall performance of the model for OATP1B1 and OATP1B1*15 was
      ?80%, including evaluation with a true external test set. Our Bayesian
      classification model thus represents a fast, inexpensive and robust means of
      assessing potential binding of new chemical entities to OATP1B1 and OATP1B1*15.
      As such, this model may be used to rank compounds early in the drug development
      process, helping to avoid adverse effects in a later stage due to inhibition of
      OATP1B1 and/or OATP1B1*15. 

PMID- 25603032
TI  - Comment on: Diagnostic accuracies of sialography and salivary ultrasonography in
      Sjogren's syndrome patients: a meta-analysis. by Song and Lee (2014).

PMID- 25603033
TI  - Update on management of heart failure with preserved ejection fraction.
AB  - PURPOSE OF REVIEW: The number of patients developing heart failure is increasing
      dramatically, and will likely continue to do so for the next few decades. At
      least half of the patients with symptoms and signs of heart failure have a normal
      left ventricular ejection fraction on echocardiography [heart failure with
      preserved ejection fraction (HFPEF)]. This review updates the current management
      of patients with HFPEF and summarizes what is in development. RECENT FINDINGS:
      Many different pathophysiologies may result in HFPEF. No single imaging measure
      may reliably identify cardiac dysfunction, but plasma concentrations of
      natriuretic peptides, reflecting the final pathway of congestion, appear to.
      Natriuretic peptides are now an essential part of the diagnostic process and are
      increasingly used to select patients to be enrolled in clinical trials. No
      therapeutic intervention has unequivocally been shown to modify the natural
      history of HFPEF, although several improve symptoms and functional capacity,
      which are important targets in this population. The failure of many clinical
      trials may reflect the inclusion of patients who are at low risk of
      cardiovascular events or the diverse pathophysiology of HFPEF. When patients are
      congested (i.e. have elevated plasma concentrations of natriuretic peptides) a
      diagnosis of HFPEF can be made with some confidence, the patients will be at
      increased cardiovascular risk and treatments aimed at correcting congestion will
      probably be effective. Selection of treatment to target a specific underlying
      pathophysiology is an alternative, relatively untried approach. SUMMARY: Further
      clinical trials will provide new insights into the pathophysiology of this
      complex disease and, hopefully, identify therapies that also improve outcome.

PMID- 25603034
TI  - Plasma polymer-functionalized silica particles for heavy metals removal.
AB  - Highly negatively charged particles were fabricated via an innovative plasma
      assisted approach for the removal of heavy metal ions. Thiophene plasma
      polymerization was used to deposit sulfur-rich films onto silica particles
      followed by the introduction of oxidized sulfur functionalities, such as
      sulfonate and sulfonic acid, via water-plasma treatments. Surface chemistry
      analyses were conducted by X-ray photoelectron spectroscopy and time-of-flight
      secondary ion mass spectroscopy. Electrokinetic measurements quantified the zeta
      potentials and isoelectric points (IEPs) of modified particles and indicated
      significant decreases of zeta potentials and IEPs upon plasma modification of
      particles. Plasma polymerized thiophene-coated particles treated with water
      plasma for 10 min exhibited an IEP of less than 3.5. The effectiveness of
      developed surfaces in the adsorption of heavy metal ions was demonstrated through
      copper (Cu) and zinc (Zn) removal experiments. The removal of metal ions was
      examined through changing initial pH of solution, removal time, and mass of
      particles. Increasing the water plasma treatment time to 20 min significantly
      increased the metal removal efficiency (MRE) of modified particles, whereas
      further increasing the plasma treatment time reduced the MRE due to the influence
      of an ablation mechanism. The developed particulate surfaces were capable of
      removing more than 96.7% of both Cu and Zn ions in 1 h. The combination of plasma
      polymerization and oxidative plasma treatment is an effective method for the
      fabrication of new adsorbents for the removal of heavy metals. 

PMID- 25603035
TI  - Treating to target in psoriatic arthritis.
AB  - PURPOSE OF REVIEW: Psoriatic arthritis (PsA) is an inflammatory arthritis causing
      significant joint damage and impaired quality of life. A treat to target approach
      has revolutionized the care of patients with rheumatoid arthritis over the last
      decade. There is now increasing interest in a similar approach in PsA, as it
      seems that ongoing joint inflammation predicts subsequent damage and loss of
      function. RECENT FINDINGS: A 2011 European League Against Rheumatism review
      highlighted a lack of evidence for treat to target in PsA. However, with the
      development of the minimal disease activity criteria, a target is available and
      preliminary results from the first randomized treat-to target study (Tight
      Control of PsA Study) using these criteria have shown significant benefit in
      joint and skin disease activity and patient-reported outcomes. SUMMARY: Early
      evidence has shown the potential benefit of a treat-to-target approach in PsA and
      further research is needed to optimize treatment pathways for all subtypes of the
      disease.

PMID- 25603036
TI  - Targeting extra-articular manifestations in PsA: a closer look at enthesitis and
      dactylitis.
AB  - PURPOSE OF REVIEW: Enthesitis and dactylitis are cardinal manifestations of
      psoriatic arthritis (PsA), but a limited understanding of underlying
      pathophysiologic mechanisms has hindered development of targeted therapies. This
      gap is of clinical relevance because these manifestations are clinically relevant
      to patients. Herein, we discuss new exciting findings in animal models with
      enthesitis and dactylitis, summarize developments in clinical and imaging
      assessments and review recent clinical trial data on the efficacy of targeted
      therapies for enthesitis and dactylitis. RECENT FINDINGS: Several different
      animal models reveal that cytokines in the interleukin-23/Th17 pathway and
      mechanical stress are key events in the development of enthesitis and dactylitis.
      Elevated levels of interleukin-23, generated in the gut, joint or skin, trigger
      subsequent tissue inflammation. Both enthesitis and dactylitis involve
      heterogeneous tissues, associate with specific Class I Major Histocompatibility
      Complex alleles, and enthesitis may be critical for the development of PsA,
      although a causal pathway remains unproven. Diagnosis is based on clinical and
      imaging assessments; however, Power Doppler ultrasound (PDUS) is more sensitive
      for diagnosis and longitudinal follow-up of enthesitis. Agents targeting tumor
      necrosis factor, interleukin-12/23, interleukin-17, interleukin-17 receptor
      (interleukin-17R) and PDE4 are effective therapies for psoriatic enthesitis and
      dactylitis. SUMMARY: Novel preclinical models established, for the first time,
      the importance of the interleukin-23/Th17 pathway and mechanical stress in
      pathogenesis of dactylitis and enthesitis. Advances in imaging, particular
      (PDUS), may improve sensitivity and specificity for diagnosis and longitudinal
      assessments. Many targeted therapies are effective for enthesitis and dactylitis.

PMID- 25603037
TI  - Combination conventional DMARDs compared to biologicals: what is the evidence?
AB  - PURPOSE OF REVIEW: Dramatic improvement seen in the prognosis of rheumatoid
      arthritis has been driven by higher expectations, led by newer drugs and more
      intensive use of the older drugs. Although methotrexate has retained its place as
      the first-line agent, there has been great interest in comparing biologicals to
      conventional Disease Modifying Anti Rheumatic Drugs (DMARDs) over the past few
      years with the updated guidelines from both the American College of Rheumatology
      and European League Against Rheumatism. We have tried to critically summarize the
      findings of some landmark trials that compare these two approaches. RECENT
      FINDINGS: Treatment of Early Rheumatoid Arthritis, The Swedish Pharmacotherapy
      study and Rheumatoid Arthritis Comparison of Active Therapies are landmark trials
      that were designed to compare strategies using biologicals vs. conventional
      DMARDs. We will review the safety and efficacy data from these three trials here
      and also briefly the important cost differential. CONCLUSION: Methotrexate should
      be the first-line therapy for most rheumatoid arthritis patients and will produce
      the desired results in greater than one-third of the patients. When methotrexate
      is not adequate, triple DMARD therapy should be added which will result in
      control of approximately another one-third of the patients. Ultimately, and
      usually before 1 year of disease, the remainder of patients will require
      biological therapies usually added to conventional DMARDs. There is no evidence
      that this step-up approach results in any long-term disadvantage and good
      evidence that it results in substantial cost savings.

PMID- 25603038
TI  - Targeting cell migration in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: To provide an update of past failures, future prospects and
      key challenges facing the therapeutic targeting of chemokines and their receptors
      in rheumatoid arthritis. RECENT FINDINGS: Clinical trials in rheumatoid arthritis
      have been undertaken with small molecule antagonists or neutralizing antibodies
      targeting CCR1, CCR5 and CXCL10. Some encouraging results have emerged.
      Laboratory and clinical research has identified CCL19, CXCL13 and CXCL12, and
      their receptors, as potential future targets. Developments in our appreciation of
      posttranslational chemokine modification highlight the complexity of chemokine
      networks operating in inflamed tissues, and the substantial gaps in existing
      knowledge. SUMMARY: Despite previous disappointments, there are still reasons to
      be optimistic that drugs targeting chemokines and their receptors could be
      developed for the treatment of rheumatoid arthritis. However, a deeper
      understanding of the chemokine networks at work in inflamed joints is a necessary
      prerequisite.

PMID- 25603039
TI  - New medications in development for the treatment of hyperuricemia of gout.
AB  - PURPOSE OF REVIEW: To update recent developments in medications targeting
      hyperuricemia, but not including medications recently labelled in the European
      Union and the United States. RECENT FINDINGS: A new xanthine oxidase inhibitor,
      Topiloric (Fujiyakuhin Co., Ltd. Japan) Uriadec (Sanwa Kagaku Kenkyusho Co., Ltd.
      Japan), has been developed and labelled in Japan. An inhibitor of purine
      nucleoside phosphorylase, Ulodesine, is in development in combination with
      allopurinol. The rest of the medications in the pipeline for hyperuricemia are
      targeting renal transporters of uric acid, mainly URAT1 and OAT4, acting as
      uricosuric agents. Most of them, such as lesinurad and arhalofenate, are being
      tested in trials in combination with allopurinol and febuxostat. The most potent
      RDEA3170 is being tested in monotherapy, but also associated with febuxostat.
      Recently, medications showing dual activity, inhibiting both xanthine
      oxidoreductase and URAT1, have been communicated or started exploratory clinical
      trials. There is no report of medications targeting other transporters such as
      Glut9 or ABCG2. SUMMARY: There are a number of medications in the pipeline
      targeting hyperuricemia, mostly uricosurics in combination with xanthine oxidase
      inhibitors, but some targeting both xanthine oxidoreductase and URAT1. Increasing
      the number of available medications will ensure proper control of hyperuricemia
      to target serum urate levels in the near future for most, if not all, patients
      with hyperuricemia.

PMID- 25603040
TI  - Recognizing and managing comorbidities in psoriatic arthritis.
AB  - PURPOSE OF REVIEW: Many patients with psoriatic arthritis (PsA) have additional
      medical problems that can have an impact on morbidity and mortality. The goal of
      this review is to summarize the available evidence to date on the association of
      medical comorbidities with PsA and the implications these comorbidities have on
      prognosis, therapy selection and treatment response. RECENT FINDINGS:
      Cardiovascular disease, metabolic syndrome, obesity, diabetes, fatty liver
      disease Crohn's disease, ophthalmic disease, depression and anxiety are common
      comorbidities associated with PsA. Additional comorbidities may include an
      elevated risk for malignancy and osteoporosis; however, fewer studies have
      addressed these issues and the data available are sometimes conflicting. SUMMARY:
      All clinicians caring for patients with PsA should be aware of the relevant
      comorbidities affecting patients with PsA and should have an understanding of how
      these comorbidities affect management.

PMID- 25603041
TI  - The role of the synovial fibroblast in rheumatoid arthritis pathogenesis.
AB  - PURPOSE OF REVIEW: Synovial fibroblasts continue to grow in prominence both as
      the subjects of research into the pathogenesis of rheumatoid arthritis and as
      novel therapeutic targets. This timely review aims to integrate the most recent
      findings with existing paradigms of fibroblast-related mechanisms of disease.
      RECENT FINDINGS: Linking the role of synovial fibroblasts as innate sentinels
      expressing pattern recognition receptors such as toll-like receptors to their
      effector roles in joint damage and interactions with leukocyte subpopulations has
      continued to advance. Understanding of the mechanisms underlying increased
      fibroblast survival in the inflamed synovium has led to therapeutic strategies
      such as cyclin-dependent kinase inhibition. Major advances have taken place in
      understanding of the interactions between epigenetic and micro-RNA regulation of
      transcription in synovial fibroblasts, improving our understanding of the unique
      pathological phenotype of these cells. Finally, the impact of new markers for
      fibroblast subpopulations is beginning to become apparent, offering the potential
      for targeting of pathological cells as the roles of different populations become
      clearer. SUMMARY: Over the past 2 years, major advances have continued to emerge
      in understanding of the relationship between synovial fibroblasts and the
      regulation of inflammatory pathways in the rheumatoid arthritis synovium.

PMID- 25603042
TI  - FDA regulation of adult stem cell therapies as used in sports medicine.
AB  - In sports medicine, adult stem cells are the subject of great interest. Several
      uses of stem cells are under investigation including cartilage repair, meniscal
      regeneration, anterior cruciate ligament reconstruction, and tendinopathy.
      Extensive clinical and basic science research is warranted as stem cell therapies
      become increasingly common in clinical practice. In the United States, the Food
      and Drug Administration (FDA) is responsible for regulating the use of stem cells
      through its "Human Cells, Tissues, and Cellular and Tissue-Based Products"
      regulations. This report provides a brief overview of FDA regulation of adult
      stem cells. Several common clinical case scenarios are then presented that
      highlight how stem cells are currently being used in sports medicine and how
      current FDA regulations are likely to affect the physicians who use them. In the
      process, it explains how a variety of factors in sourcing and handling these
      cells, particularly the extent of cell manipulation, will affect what a physician
      can and cannot do without first obtaining the FDA's express approval. 

PMID- 25603043
TI  - Size-tuned ZnO nanocrucible arrays for magnetic nanodot synthesis via atomic
      layer deposition-assisted block polymer lithography.
AB  - Low-temperature atomic layer deposition of conformal ZnO on a self-assembled
      block polymer lithographic template comprising well-ordered, vertically aligned
      cylindrical pores within a poly(styrene) (PS) matrix was used to produce
      nanocrucible templates with pore diameters tunable via ZnO thickness. Starting
      from a PS template with a hexagonal array of 30 nm diameter pores on a 45 nm
      pitch, the ZnO thickness was progressively increased to narrow the pore diameter
      to as low as 14 nm. Upon removal of the PS by heat treatment in air at 500 
      degrees C to form an array of size-tunable ZnO nanocrucibles, permalloy
      (Ni80Fe20) was evaporated at normal incidence, filling the pores and creating an
      overlayer. Argon ion beam milling was then used to etch back the overlayer (a
      Damascene-type process), leaving a well-ordered array of isolated ZnO
      nanocrucibles filled with permalloy nanodots. Microscopy and temperature
      dependent magnetometry verified the diameter reduction with increasing ZnO
      thickness. The largest diameter (30 nm) dots exhibit a ferromagnetic
      multidomain/vortex state at 300 K, with relatively weakly temperature-dependent
      coercivity. Reducing the diameter leads to a crossover to a single-domain state
      and eventually superparamagnetism at sufficiently high temperature, in
      quantitative agreement with expectations. We argue that this approach could
      render this form of block polymer lithography compatible with high-temperature
      processing (as required for technologically important high perpendicular
      anisotropy ordered alloys, for instance), in addition to enabling separation
      dependent studies to probe interdot magnetostatic interactions. 

PMID- 25603044
TI  - Aberrant cerebellar development of transgenic mice expressing dominant-negative
      thyroid hormone receptor in cerebellar Purkinje cells.
AB  - To study the role of the thyroid hormone (TH) in cerebellar development, we
      generated transgenic mice expressing a dominant-negative TH receptor (TR) in
      cerebellar Purkinje cells. A mutant human TRbeta1 (G345R), which binds to the TH
      response element but cannot bind to T3, was subcloned into exon 4 of the full
      length L7/Pcp-2 gene, which is specifically expressed in Purkinje and retinal rod
      bipolar cells. The transgene was specifically expressed in Purkinje cells in the
      postnatal cerebellum. Purkinje cell dendrite arborization was significantly
      delayed in the transgenic mice. Surprisingly, granule cell migration was also
      significantly delayed. In the primary cerebellar culture, TH-induced Purkinje
      cell dendrite arborization was also suppressed. In quantitative real-time RT-PCR
      analysis, the expression levels of several TH-responsive genes were altered. The
      expression levels of inositol trisphosphate receptor type 1 and retinoic acid
      receptor-related orphan receptoralpha mRNAs, which are mainly expressed in
      Purkinje cells, and brain-derived neurotrophic factor mRNA, which is expressed in
      both Purkinje and granule cells, were significantly decreased. The expression
      levels of neurotrophin-3 and hairless mRNAs, which are mainly expressed in
      granule cells, and myelin basic protein mRNA, which is mainly expressed in
      oligodendrocytes, were also decreased. The motor coordination of transgenic mice
      was significantly disrupted. These results indicate that TH action through its
      binding to TR in Purkinje cells is required for the normal cerebellar
      development. TH action through TR in Purkinje cells is also important for the
      development of other subsets of cerebellar cells such as granule cells and
      oligodendrocytes. 

PMID- 25603045
TI  - Androgens inhibit aromatase expression through DAX-1: insights into the molecular
      link between hormone balance and Leydig cancer development.
AB  - Leydig cell tumors (LCTs) of the testis are steroid-secreting tumors associated
      with various steroid biosynthetic abnormalities and endocrine dysfunctions.
      Despite their overall rarity, LCTs are still of substantial interest owing to the
      paucity of information regarding their exact nature and malignant potential. In
      the present study, we disclose the ability of androgens to inhibit Leydig tumor
      cell proliferation by opposing to self-sufficient in situ estrogen production. In
      rat Leydig tumor cells, R2C, androgen treatment significantly decreases the
      expression and the enzymatic activity of cytocrome P450 aromatase, responsible
      for the local conversion of androgens into estrogens. This inhibitory effect
      relies on androgen receptor (AR) activation and involves negative regulation of
      the CYP19 gene transcriptional activity through the nuclear orphan receptor DAX-1
      (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome
      X, gene 1). Ligand-activated AR up-regulates the expression of DAX-1 and promotes
      its increased recruitment within the steroidogenic factor-1 site-containing
      region of the aromatase proximal promoter II in association with the nuclear
      receptor corepressor. The biological relevance in LCTs of the newly highlighted
      functional interplay between AR, DAX-1, and aromatase is underlined by our in
      vivo observations, revealing a marked down-regulation of AR and DAX-1 expression
      and a strong increase in aromatase levels in testes tissues from old Fischer rats
      with spontaneously developed Leydig cell neoplasia, compared with normal testes
      tissues from younger animals. In elucidating a mechanism by which androgens
      modulate the growth of Leydig tumor cells, our finding support the hypothesis
      that maintaining the adequate balance between androgen and estrogens may
      represent the key for blocking estrogen-secreting Leydigioma development, opening
      new prospects for therapeutic intervention. 

PMID- 25603047
TI  - Type II anti-CD20 mAb-induced lysosome mediated cell death is mediated through a
      ceramide-dependent pathway.
AB  - In the past decade, monoclonal antibodies (mAbs) have revolutionized the
      treatment of non-Hodgkin lymphomas (NHLs). Although Fc-dependent mechanisms of
      mAb-mediated tumor clearance have been extensively studied, the ability of mAbs
      to directly evoke programmed cell death (PCD) and the underlying mechanisms
      involved remain unclear. It is well established that type II anti-CD20 mAb
      (Tositumomab) potently evoked PCD through a caspases-independent, lysosome
      mediated process, which is related to homotypic adhesion (HA) in NHL cell lines.
      Herein, we reveal that the induction of ceramide generation by anti-CD20 mAbs
      directly correlates with their ability to induce PCD. The inhibition of ceramide
      abrogated Tositumomab-induced PCD indicating that ceramide is required for the
      execution of cell death. Further experimental results revealed that ceramide was
      generated downstream of mAb-induced HA and upstream of lysosome leakage. These
      findings provide further insights into a previously unrecognized role for
      ceramide generation in mediating PCD evoked by type II anti-CD20 mAbs in
      Burkitt's lymphoma cells. This newly characterized cell death pathway may
      potentially be exploited to eliminate malignant cells. 

PMID- 25603048
TI  - ABCB1, ABCC1, and LRP gene expressions are altered by LDL, HDL, and serum
      deprivation in a human doxorubicin-resistant uterine sarcoma cell line.
AB  - Multidrug resistance (MDR) is the major cause of cancer treatment failure. The
      ATP-binding cassette-B1 (ABCB1) transporter, also known as MDR1 or P
      glycoprotein, is thought to promote the efflux of drugs from cells. MDR is also
      associated with the multidrug resistance-associated protein 1 (ABCC1) and the
      lung resistance-related protein (LRP), a human major vault protein. Moreover, MDR
      has a complex relationship with lipids. The ABCB1 has been reported to modulate
      cellular cholesterol homeostasis. Conversely, cholesterol has been reported to
      modulate multidrug transporters. However, results reported to date are
      contradictory and confusing. The aim of this study was to investigate whether
      LDL, HDL, and serum deprivation could influence ABCB1, ABCC1, and LRP expression
      in a human doxorubicin-resistant uterine sarcoma cell line. ABCB1 and ABCC1
      expression increased after 24 h of serum deprivation, and expression returned to
      basal levels after 72 h. LDL, depending on concentration, increased ABCB1, ABCC1,
      and LRP expression. ABCB1 expression increased at low HDL, and decreased at high
      HDL concentrations. We demonstrated that serum deprivation and lipoproteins,
      particularly LDL, modulated ABCB1 expression and, to a lesser extent, ABCC1
      expression. This finding may link the phenomena of drug transport, cholesterol
      metabolism and cancer.

PMID- 25603046
TI  - Impact of gestational bisphenol A on oxidative stress and free fatty acids: Human
      association and interspecies animal testing studies.
AB  - Bisphenol A (BPA) is a high production volume chemical and an endocrine
      disruptor. Developmental exposures to BPA have been linked to adult metabolic
      pathologies, but the pathways through which these disruptions occur remain
      unknown. This is a comprehensive interspecies association vs causal study to
      evaluate risks posed by prenatal BPA exposure and to facilitate discovery of
      biomarkers of relevance to BPA toxicity. Samples from human pregnancies during
      the first trimester and at term, as well as fetal and/or adult samples from
      prenatally BPA-treated sheep, rats, and mice, were collected to assess the impact
      of BPA on free fatty acid and oxidative stress dynamics. Mothers exposed to
      higher BPA during early to midpregnancy and their matching term cord samples
      displayed increased 3-nitrotyrosine (NY), a marker of nitrosative stress.
      Maternal samples had increased palmitic acid, which was positively correlated
      with NY. Sheep fetuses and adult sheep and rats prenatally exposed to a human
      relevant exposure dose of BPA showed increased systemic nitrosative stress. The
      strongest effect of BPA on circulating free fatty acids was observed in adult
      mice in the absence of increased oxidative stress. This is the first multispecies
      study that combines human association and animal causal studies assessing the
      risk posed by prenatal BPA exposure to metabolic health. This study provides
      evidence of the induction of nitrosative stress by prenatal BPA in both the
      mother and fetus at time of birth and is thus supportive of the use of maternal
      NY as a biomarker for offspring health.

PMID- 25603049
TI  - High fat diet exacerbates vascular endothelial dysfunction in rats exposed to
      continuous hypobaric hypoxia.
AB  - Independently, a high fat diet and hypoxia are associated with vascular
      endothelial dysfunction (VED) and often occur concurrently in patients.
      Nevertheless, the effects of a high fat diet on vascular endothelial function
      combined with hypoxia, a situation occurring with increasing frequency in many
      parts of the world, remain largely unknown. We investigated the effects of a high
      fat diet on vascular endothelial function in rats exposed to continuous hypoxia
      for 4 weeks. Seventy two male Sprague-Dawley rats were randomly divided into 3
      groups: a hypoxia group fed regular chow, a combined hypoxia and high fat diet
      (HFD) group, and for comparison, rats maintained in normoxia, regular chow
      conditions were set as baseline (BL) group. The experimental data of BL group
      were obtained at beginning of hypoxia given in the other groups. Continuous
      hypoxia was induced in a hypobaric chamber maintained at an altitude of 5000 m.
      Compared to hypoxic conditions alone, hypoxia plus a HFD prevented adaptive
      changes in plasma nitric oxide (NOx) levels and caused earlier and more severe
      changes in aortic endothelial structures. Functionally, hypoxia plus a HFD
      resulted in impaired endothelium-dependent vasorelaxation responses to
      acetylcholine and altered the bioavailability of the nitric oxide synthase (NOS)
      substrate L-Arginine. At the molecular level, hypoxia plus a HFD blunted
      increases in endothelial NOS (eNOS) mRNA and protein in aortic endothelial
      tissue. Taken together, our findings demonstrate that in the setting of hypoxia,
      a high fat diet leads to earlier and more severe VED than hypoxia alone. These
      data have important implications for populations residing at high-altitude, as
      dietary patterns shift towards increased fat intake.

PMID- 25603050
TI  - MiR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary
      thyroid carcinoma.
AB  - microRNAs (miRNAs) are frequently dysregulated in human malignancies. It was
      recently shown that miR-204-5p is downregulated in papillary thyroid carcinoma
      (PTC); however, the functional significance of this observation is not known.
      This study investigated the role of miR-204-5p in PTC. Overexpressing miR-204-5p
      suppressed PTC cell proliferation and induced cell cycle arrest and apoptosis.
      The results of a luciferase reporter assay showed that miR-204-5p can directly
      bind to the 3' untranslated region (UTR) of insulin-like growth factor-binding
      protein 5 (IGFBP5) mRNA, and IGFBP5 overexpression partially reversed the growth
      inhibitory effects of miR-204-5p. These results indicate that miR-204-5p acts as
      a tumor suppressor in PTC by regulating IGFBP5 expression and that miR-204-5p can
      potentially serve as an antitumorigenic agent in the treatment of PTC. 

PMID- 25603051
TI  - Glycerol 3-phosphate dehydrogenase 1 deficiency enhances exercise capacity due to
      increased lipid oxidation during strenuous exercise.
AB  - A large percentage of energy produced during high-intensity exercise depends on
      the aerobic glycolytic pathway. Maintenance of a cytoplasmic redox balance
      ([NADH]/[NAD(+)] ratio) by the glycerophosphate shuttle involves sustained
      aerobic glycolysis. Glycerol 3-phosphate dehydrogenase 1 (GPD1) catalyzes an
      oxidation reaction in the glycerophosphate shuttle. In this study, we examined
      whether GPD1 deficiency decreases exercise capacity due to impairment of aerobic
      glycolysis by using the GPD1 null mouse model BALB/cHeA (HeA). Unexpectedly, we
      found that exercise endurance was significantly higher in HeA mice than in
      BALBc/By (By) mice used as controls. Furthermore, aerobic glycolysis in HeA mice
      was not impaired. During exercise, lipid oxidation was significantly higher in
      HeA mice than in By mice, concomitant with an increase in phosphorylation of AMP
      activated protein kinase (AMPK). HeA mice also showed a delay in the onset of
      muscle glycogen usage and lactate production during exercise. These data suggest
      that contribution of lipid oxidation as a fuel source for exercise is increased
      in HeA mice, and GPD1 deficiency enhances exercise capacity by increasing lipid
      oxidation, probably due to activation of AMPK. We propose that GPD1 deficiency
      induces an adaptation that enhances lipid availability in the skeletal muscle
      during exercise. 

PMID- 25603052
TI  - Increased extracellular and intracellular Ca2+ lead to adipocyte accumulation in
      bone marrow stromal cells by different mechanisms.
AB  - Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common
      progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis
      is associated with age-related osteopenia and anemia. Both extracellular and
      intracellular Ca(2+) ([Ca(2+)]o and [Ca(2+)]i) are versatile signaling molecules
      that are involved in the regulation of cell functions, including proliferation
      and differentiation. We have recently reported that upon treatment of BMSCs with
      insulin and dexamethasone, both high [Ca(2+)]o and high [Ca(2+)]i enhanced
      adipocyte accumulation, which suggested that increases in [Ca(2+)]o caused by
      bone resorption may accelerate adipocyte accumulation in aging and diabetic
      patients. In this study, we used primary mouse BMSCs to investigate the
      mechanisms by which high [Ca(2+)]o and high [Ca(2+)]i may enhance adipocyte
      accumulation. In the process of adipocyte accumulation, two important keys are
      adipocyte differentiation and the proliferation of BMSCs, which have the
      potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR
      revealed that high [Ca(2+)]i (ionomycin)-dependent adipocyte accumulation is
      caused by enhanced proliferation of BMSCs but not enhanced differentiation into
      adipocytes. Using fura-2 fluorescence-based approaches, we showed that high
      [Ca(2+)]o (addition of CaCl2) leads to increases in [Ca(2+)]i. Flow cytometric
      methods revealed that high [Ca(2+)]o suppressed the phosphorylation of ERK
      independently of intracellular Ca(2+). The inhibition of ERK by U0126 and
      PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data
      suggest that increased extracellular Ca(2+) provides the differentiation of BMSCs
      into adipocytes by the suppression of ERK activity independently of increased
      intracellular Ca(2+), which results in BMSC proliferation.

PMID- 25603053
TI  - Resveratrol induces cell apoptosis in adipocytes via AMPK activation.
AB  - Resveratrol is identified as polyphenolic compound with anti-inflammatory,
      antioxidant, anti-insulin resistance characteristics. Moreover, resveratrol
      exerts pro-apoptotic effects in varieties of cancer cell lines. However, effects
      and mechanisms of resveratrol on the regulation of adipocytes apoptosis remain
      largely unknown. In this study, we found that resveratrol treatment could induce
      cell apoptosis in murine 3T3-L1 adipocytes. Furthermore, resveratrol activated
      the mitochondrial apoptotic signaling pathway with the decrease in the
      mitochondrial membrane potential (MMP), and the activation of caspase 3.
      Mechanistically, we found that phosphorylation level of AMP-activated protein
      kinase alpha (AMPKalpha) was elevated, accompany with reduced level of
      phosphorylation of protein kinase B (AKT) when cells were exposed to resveratrol.
      By using small interfering RNAs of AMPKalpha and specific inhibitor for p-AKT, it
      was shown that activation of AMPKalpha could inhibit downstream of p-AKT,
      consequently activating mitochondrion-mediated apoptotic pathway. Additionally,
      we observed similar pro-apoptotic effects of Res on mouse primary adipocytes. Our
      findings clarified the apoptotic effects and underlying mechanisms of resveratrol
      in adipocytes, suggesting its potential therapeutic application in the treatment
      or prevention of obesity and related metabolic symptoms.

PMID- 25603054
TI  - The perivascular phenotype and behaviors of dedifferentiated cells derived from
      human mature adipocytes.
AB  - Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a
      special group of multipotent cells. However, their phenotype and cellular nature
      remain unclear. Our study found that human DFAT cells adopted perivascular
      characteristics and behaviors. Flow cytometry and immunofluorescent staining
      revealed that human DFAT cells positively expressed markers highly related to
      perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for
      common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT
      cells displayed vascular network formation ability in Matrigel, and they
      noticeably promoted and stabilized the vessel structures formed by human
      umbilical vascular endothelial cells (HUVECs) in vitro. These results provide
      novel evidence on the pericyte nature of human DFAT cells, further supporting the
      recent model for the perivascular origin of adult stem cells, in which tissue
      specific progenitor cells in mesenchymal tissues associate with blood vessels,
      exhibiting perivascular characteristics and functions.

PMID- 25603055
TI  - HIF-1alpha suppressing small molecule, LW6, inhibits cancer cell growth by
      binding to calcineurin b homologous protein 1.
AB  - Hypoxia inducible factor-1 alpha (HIF-1alpha) plays an important role in
      angiogenesis and metastasis and is a promising therapeutic target for the
      development of anti-cancer drugs. We recently developed a new synthetic small
      molecule inhibitor of HIF-1alpha, LW6, which results in inhibition of
      angiogenesis. To investigate its underlying mechanism, target protein
      identification was conducted by reverse chemical proteomics using phage display.
      We identified calcineurin b homologous protein 1 (CHP1) as a target protein of
      LW6, which specifically binds to CHP1 in a Ca(2+) dependent manner. Covalent
      labeling of LW6 using photoaffinity and click chemistry demonstrated its co
      localization with CHP1 in live cells. HIF-1alpha was decreased by CHP1 knockdown
      in HepG2 cells, and angiogenesis was not induced in HUVEC cells by treatment with
      conditioned media from CHP1 knockdown cells compared to the control. These data
      demonstrated that LW6 inhibited HIF-1alpha stability via direct binding with CHP1
      resulting in suppression of angiogenesis, providing a new insight into the role
      of CHP1 in HIF-1alpha regulation. LW6 could serve as a new chemical probe to
      explore CHP1 function. 

PMID- 25603056
TI  - In vitro selection and characterization of deoxyribonucleic acid aptamers against
      connective tissue growth factor.
AB  - Connective tissue growth factor (CTGF) is a secreted matricellular protein
      possessing complex biological functions. CTGF modulates a number of signaling
      pathways that are involved in cell adhesion, migration, angiogenesis,
      myofibroblast activation, extracellular matrix deposition and tissue remodeling.
      Aptamers are oligonucleic acid chains or polypeptides that bind with specific
      target molecules hence have the potential to be used in the detection and
      blockade of the targets. In this study, we selected CTGF-targeting DNA aptamers
      by using systematic evolution of ligands by exponential enrichment (SELEX). After
      8 iterative rounds of selection, cloning, DNA sequencing and affinity
      determination, six aptamers with high affinities to CTGF were obtained. Among
      them, one (C-ap17P) binds with the N-terminal region (aa 1-190) and the other
      five (C-ap11, 12, 14, 15 and 18) bind with the C-terminal region (aa 191-350) of
      hCTGF specifically. The biological stability assay indicated that a
      representative aptamer, C-ap17P, could keep its integrity at a rather high level
      for at least 24 h in complete DMEM cell culture medium. These CTGF aptamers might
      be used as a easy and fast detection tool for CTGF and be developed as CTGF
      specific inhibitors for both research works and clinical applications.

PMID- 25603058
TI  - Livestock GRACEnet: A Workgroup Dedicated to Evaluating and Mitigating Emissions
      from Livestock Production.
AB  - Ammonia, greenhouse gases, and particulate emissions from livestock operations
      can potentially affect air quality at local, regional, and even global scales.
      These pollutants, many of which are generated through various anthropogenic
      activities, are being increasingly scrutinized by regulatory authorities.
      Regulation of emissions from livestock production systems will ultimately
      increase on farm costs, which will then be passed onto consumers. Therefore, it
      is essential that scientifically based emission factors are developed for on-farm
      emissions of air quality constituents to improve inventories and assign
      appropriate reduction targets. To generate a larger database of on-farm
      emissions, the USDA-ARS created the workgroup Livestock GRACEnet (Greenhouse gas
      Reduction through Agricultural Carbon Enhancement Network). This introduction for
      the special section of papers highlights some of the research presently being
      conducted by members of Livestock GRACEnet with the intent of drawing attention
      to critical information gaps, such as (i) improving emissions measurements; (ii)
      developing emissions factors; (iii) developing and validating tools for
      estimating emissions; and (iv) mitigating emissions. We also provide a synthesis
      of the literature with respect to key research areas related to livestock
      emissions, including feeding strategies, animal housing, manure management, and
      manure land application, and discuss future research priorities and directions. 

PMID- 25603059
TI  - Optimal sensor locations for the backward lagrangian stochastic technique in
      measuring lagoon gas emission.
AB  - This study evaluated the impact of gas concentration and wind sensor locations on
      the accuracy of measuring gas emission rates from a lagoon environment using the
      backward Lagrangian stochastic (bLS) inverse-dispersion technique. Path
      integrated concentrations (PICs) and three-dimensional (3D) wind vector data were
      collected at different locations within the lagoon landscape. A floating 45 m *
      45 m perforated pipe network on an irrigation pond was used as a synthetic
      distributed emission source for the controlled release of methane. A total of 961
      15-min datasets were collected under different atmospheric stability conditions
      over a 2-yr period. The PIC location had a significant impact on the accuracy of
      the bLS technique. The location of the 3D sonic anemometer was generally not a
      factor for the measured accuracies with the PIC positioned on the downwind berm.
      The PICs across the middle of the pond consistently produced the lowest accuracy
      with any of the 3D anemometer locations (<69% accuracy). The PICs located on the
      downwind berm consistently yielded the best bLS accuracy regardless of whether
      the 3D sonic anemometer was located on the upwind, side, or downwind berm
      (accuracies ranged from 79 to 108%). The accuracies of the emission measurements
      with the berm PIC-berm 3D setting were statistically similar to that found in a
      more ideal homogeneous grass field. Considering the practical difficulties of
      setting up equipment and the accuracies associated with various sensor locations,
      we recommend that wind and concentration sensors be located on the downwind berm.

PMID- 25603060
TI  - Ammonia and nitrous oxide emissions from a commercial broiler house.
AB  - Complex variation in gas emissions from animal facilities has been shown in
      recent research reports. Uncertainties in these emission estimates are driving
      research activities concerning different animal species across the globe.
      Greenhouse gas (NO and CO) and NH concentrations were measured in a modern,
      tunnel-ventilated, commercial broiler house in Mississippi during five flocks
      (spanning approximately 1 yr). These were flocks 9 through 13 on reused pine
      shavings litter, representing litter reuse beyond 2 yr. Gas concentrations
      obtained from a photoacoustic multigas analyzer were coupled with ventilation
      measurements of air flow through the house to develop NH and NO emission rates.
      Ammonia emission during a flock (43 d) averaged approximately 14.8 +/- 9.8 kg d
      in the commercial house (equivalent to 23.5 g bird marketed or 0.54 g bird d).
      Nitrous oxide emission averaged 2.3 +/- 1.7 kg d in the house (equivalent to 3.64
      g bird marketed or 0.085 g bird d). Emission rates increased with time from Day 1
      to Day 43 and reached average values on Day 23 and 24 for NH and NO. Even with
      extended litter reuse, estimates of NH emissions from the broiler house agree
      well with recently published research that reused litter in eight or fewer
      flocks. This is important information for farmers who may not be able to afford
      to replace the litter with fresh bedding material annually. 

PMID- 25603057
TI  - Cholesterol reduces the sensitivity to platinum-based chemotherapy via
      upregulating ABCG2 in lung adenocarcinoma.
AB  - Inoperable lung adenocarcinoma is currently treated with platinum-based
      chemotherapy. However, the effectiveness of these chemotherapeutic agents is not
      the same for all patients. Patients either show quick chemoresistance (QCR) or
      delayed chemoresistance (DCR), which are defined by 87 and 242 days of
      progression-free survival (PFS) after initial platinum-based treatment,
      respectively. We found that QCR patients displayed an elevated level of serum
      cholesterol and that their tumors showed upregulated ABCG2 expression. We propose
      that chemoresistance may be attributed to cholesterol-induced ABCG2 expression
      and hypothesize that blocking ABCG2 may increase the efficacy of platinum-based
      chemotherapeutic agents. Using the MTT cell viability assay, we observed that
      cotreatment with ABCG2 blocker Nicardipine and platinum-based drugs Cisplatin,
      Oxaliplatin or Carboplatin significantly decreased cell viability of tumor cells.
      Importantly, our results also showed that incubating cells with cholesterol prior
      to chemotherapy treatment or cotreatment increased cell viability of tumor cells
      relative to the controls. 

PMID- 25603061
TI  - Methane Emissions from a Beef Cattle Feedyard during Winter and Summer on the
      Southern High Plains of Texas.
AB  - Methane (CH) emissions from enteric fermentation by livestock account for about
      2.1% of U.S. greenhouse gas emissions, with beef and dairy cattle being the most
      significant sources. A better understanding of CH emissions from beef cattle
      feedyards can help build more accurate emission inventories, improve predictive
      models, and meet potential regulatory requirements. Our objective was to quantify
      CH emissions during winter and summer at a typical beef cattle feedyard on the
      southern High Plains in Texas. Methane emissions were quantified over 32 d in
      winter and 44 d in summer using open-path lasers and inverse dispersion analysis.
      Methane per capita emission rate (PCER) ranged from 71 to 118 g animal d in
      winter and from 70 to 130 g animal d in summer. Mean CH PCER was similar in
      January, February, and May (average, 85.0 +/- 0.95 g animal d) and increased to
      93.4 g animal d during the June-July period. This increase coincided with
      increased dietary fiber. Methane loss ranged from 9.2 to 11.4 g CH kg dry matter
      intake, with lower values during winter. Gross energy intake (GEI) ranged from
      135.2 to 164.5 MJ animal d, and CH energy loss ranged from 4.5 to 4.9 MJ animal
      d. Fraction of GEI lost as CH (Y) averaged 2.8% in winter, 3.2% in summer, and
      3.0% overall. These values confirm the Y value currently recommended by the
      Intergovernmental Panel on Climate Change for Tier 2 estimates of enteric CH from
      feedlot fed cattle. 

PMID- 25603063
TI  - Ammonia emission model for whole farm evaluation of dairy production systems.
AB  - Ammonia (NH) emissions vary considerably among farms as influenced by climate and
      management. Because emission measurement is difficult and expensive, process
      based models provide an alternative for estimating whole farm emissions. A model
      that simulates the processes of NH formation, speciation, aqueous-gas
      partitioning, and mass transfer was developed and incorporated in a whole farm
      simulation model (the Integrated Farm System Model). Farm sources included manure
      on the floor of the housing facility, manure in storage (if used), field-applied
      manure, and deposits on pasture (if grazing is used). In a comprehensive
      evaluation of the model, simulated daily, seasonal, and annual emissions compared
      well with data measured over 2 yr for five free stall barns and two manure
      storages on dairy farms in the eastern United States. In a further comparison
      with published data, simulated and measured barn emissions were similar over
      differing barn designs, protein feeding levels, and seasons of the year.
      Simulated emissions from manure storage were also highly correlated with
      published emission data across locations, seasons, and different storage covers.
      For field applied manure, the range in simulated annual emissions normally
      bounded reported mean values for different manure dry matter contents and
      application methods. Emissions from pastures measured in northern Europe across
      seasons and fertilization levels were also represented well by the model. After
      this evaluation, simulations of a representative dairy farm in Pennsylvania
      illustrated the effects of animal housing and manure management on whole farm
      emissions and their interactions with greenhouse gas emissions, nitrate leaching,
      production costs, and farm profitability. 

PMID- 25603064
TI  - Process-based Modeling of Ammonia Emission from Beef Cattle Feedyards with the
      Integrated Farm Systems Model.
AB  - Ammonia (NH) volatilization from manure in beef cattle feedyards results in loss
      of agronomically important nitrogen (N) and potentially leads to
      overfertilization and acidification of aquatic and terrestrial ecosystems. In
      addition, NH is involved in the formation of atmospheric fine particulate matter
      (PM), which can affect human health. Process-based models have been developed to
      estimate NH emissions from various livestock production systems; however, little
      work has been conducted to assess their accuracy for large, open-lot beef cattle
      feedyards. This work describes the extension of an existing process-based model,
      the Integrated Farm Systems Model (IFSM), to include simulation of N dynamics in
      this type of system. To evaluate the model, IFSM-simulated daily per capita NH
      emission rates were compared with emissions data collected from two commercial
      feedyards in the Texas High Plains from 2007 to 2009. Model predictions were in
      good agreement with observations and were sensitive to variations in air
      temperature and dietary crude protein concentration. Predicted mean daily NH
      emission rates for the two feedyards had 71 to 81% agreement with observations.
      In addition, IFSM estimates of annual feedyard emissions were within 11 to 24% of
      observations, whereas a constant emission factor currently in use by the USEPA
      underestimated feedyard emissions by as much as 79%. The results from this study
      indicate that IFSM can quantify average feedyard NH emissions, assist with
      emissions reporting, provide accurate information for legislators and
      policymakers, investigate methods to mitigate NH losses, and evaluate the effects
      of specific management practices on farm nutrient balances. 

PMID- 25603065
TI  - Potential use of milk urea nitrogen to abate atmospheric nitrogen emissions from
      wisconsin dairy farms.
AB  - Urinary urea N (UUN) is the principal nitrogen (N) source controlling emissions
      of ammonia (NH) and nitrous oxide (NO) from dairy manure. The objectives of this
      study were (i) to study the integrative nature of dietary crude protein (CP)
      management, secretion of milk urea N (MUN), excretion of UUN, and N emissions
      from dairy production systems; (ii) to evaluate how associative changes in
      dietary CP, MUN, and UUN affect atmospheric N emissions from dairy farms; and
      (iii) to discuss some of the challenges and opportunities to an expanded use of
      MUN to enhance dietary CP use and decrease UUN excretion and N emissions from
      dairy farms. Milk urea N records of 37,889 cows in 197 herds in Wisconsin
      revealed that approximately one half of tested cows were likely consuming dietary
      CP in excess of requirement. Farm simulations were used to quantify the effect of
      dietary CP on whole-farm N emissions. At a statewide average MUN of 12.5 mg dL,
      48 to 87% of UUN was emitted as NH, with the lowest loss from pasture-based farms
      and the greatest loss from tie-stall farms. Each 1 mg dL decrease of MUN (range,
      16-10 mg dL) provided an associated daily decrease in UUN of 16.6 g per cow,
      which decreased NH and NO emissions from manure by 7 to 12%. Although more site
      specific information is required on herd MUN-UUN relationships and more a
      reliable interpretation of MUN assay results is needed, monitoring of MUN may be
      used to enhance dietary CP use and to reduce UUN excretion and N emissions from
      Wisconsin dairy farms. 

PMID- 25603066
TI  - Emissions of greenhouse gases, ammonia, and hydrogen sulfide from pigs fed
      standard diets and diets supplemented with dried distillers grains with solubles.
AB  - Swine producers are supplementing animal diets with increased levels of dried
      distillers grains with solubles (DDGS) to offset the cost of a standard corn
      soybean meal (CSBM) diet. However, the environmental impact of these diets on
      emissions of greenhouse gases, ammonia (NH), and hydrogen sulfide (HS) is largely
      unknown. Twenty-four pigs (103.6 kg initial body weight) were fed a standard CSBM
      diet or a CSBM diet containing 35% DDGS for 42 d. Pigs were fed and their manure
      was collected twice daily over the 42-d trial. Pigs fed diets containing DDGS had
      reduced manure pH ( < 0.01), increased surface crust coverage ( < 0.01),
      increased manure dry matter content ( < 0.01), and increased manure C ( < 0.01),
      N ( < 0.01), and S ( < 0.01) contents. Animals fed DDGS diets also had
      significantly higher concentrations of total ammoniacal nitrogen ( < 0.01) and
      sulfide ( < 0.01) in their manure compared with animals fed CSBM diets. Manure
      emissions of NH ( < 0.01) and HS ( < 0.05) were significantly higher in animals
      fed the CSBM diet. There was no dietary treatment effect for methane or nitrous
      oxide emissions from manure. This study demonstrates that diets containing DDGS
      can significantly affect manure composition and potentially lower emissions of NH
      and HS. 

PMID- 25603067
TI  - Use of wood-based materials in beef bedded manure packs: 1. Effect on ammonia,
      total reduced sulfide, and greenhouse gas concentrations.
AB  - The objectives of this study were to determine the effect of using corn stover or
      three different wood-based bedding materials (kiln-dried pine wood chips, dry
      cedar chips, or green cedar chips) on airborne concentrations of NH, total
      reduced sulfides (TRS), CO, CH, and NO above lab-scaled bedded manure packs. Four
      bedded packs of each bedding material were maintained for two 42-d periods.
      Airborne NH, TRS, CO, CH, and NO were measured weekly. Bedded packs containing
      dry or green cedar had lower concentrations of NH (350.8 and 357.3 mg m,
      respectively; < 0.05) than bedded packs containing pine chips or corn stover
      (466.0 and 516.7 mg m, respectively). Airborne CO was also lower from bedded
      packs containing dry and green cedar (1343.7 and 1232.3 mg m, respectively; <
      0.001) compared with bedded packs containing pine chips or corn stover (2000.2
      and 1659.8 mg m, respectively). Air samples from bedded packs containing green
      cedar chips had a higher ( < 0.01) concentration of CH than bedded packs
      containing dry cedar chips, corn stover, or pine chips at Day 35 and 42.
      Initially, TRS concentration was similar among all bedding materials; at 28 to 42
      d, TRS was higher ( < 0.001) from bedded packs containing the cedar products.
      Airborne NO was similar ( = 0.51) for all bedding materials. Pine chips and cedar
      products can be adequate substitutes for corn stover in deep-bedded barns, but
      cedar bedding may need to be removed more frequently. 

PMID- 25603068
TI  - Use of wood-based materials in beef bedded manure packs: 2. Effect on odorous
      volatile organic compounds, odor activity value, , and nutrient concentrations.
AB  - The objectives of this study were to determine the effects of three types of wood
      based bedding materials (kiln-dried pine wood chips, dry cedar chips, and green
      cedar chips) and corn stover on the concentration of odorous volatile organic
      compounds (VOCs) and total in bedded pack material. Four bedded packs of each
      bedding material were maintained for two 42-d periods ( = 32; eight
      replicates/bedding material). Straight- and branched-chained fatty acids,
      aromatic compounds, and sulfide compounds were measured from the headspace above
      each bedded pack. Green cedar bedding had the highest concentration of odorous
      VOCs, and pine chip bedding had the lowest ( < 0.01). Calculated odor activity
      values were highest for green cedar bedding, followed by dry cedar, corn stover,
      and pine chip bedding. As the bedded packs aged, the concentration of odorous
      VOCs increased, particularly in the bedded packs containing green cedar chips and
      dry cedar chips. Total concentrations increased from Days 0 to 21 and then began
      to decline and were similar among all bedding materials ( < 0.10). Results of
      this study indicate that producers using a long-term bedded pack management in
      their facility may benefit from using pine chips because they do not appear to
      increase odor over time. Cedar-based bedding materials may be better suited for a
      scrape-and-haul system, where the bedded pack is removed after 1 or 2 wk. Total
      concentrations did not differ between any of the four bedding materials over
      time. 

PMID- 25603069
TI  - Emission of volatile organic compounds after land application of cattle manure.
AB  - Beef cattle manure can serve as a valuable source of nutrients for crop
      production. However, emissions of volatile organic compounds (VOCs) after land
      application may pose an odor nuisance to downwind populations. This study was
      conducted to evaluate the effects of land application method, diet, soil moisture
      content, and time since manure application on VOC emissions. Manure was collected
      from feedlot pens where cattle were fed diets containing 0, 10, or 30% wet
      distillers grains with solubles (WDGS). Land application methods included surface
      applying manure (i.e., no-tillage) or incorporating manure using disk tillage.
      The effects of soil moisture content on VOC emissions was determined by adding
      water to each of the plots approximately 24 h after manure application.
      Isovaleric acid, butyric acid, and 4-methylphenol contributed 28.9, 18.0, and
      17.7%, respectively, of the total measured odor activity values. In general, the
      largest emissions of volatile fatty acids and aromatics were measured during the
      initial collection periods on the no-tillage plots under dry soil moisture
      conditions. Emissions of volatile fatty acids and aromatics were reduced after
      water additions because these compounds were stored in the soil-water matrix
      rather than released into the atmosphere. In contrast, sulfide emissions
      generally increased with the addition of the water, especially on the plots
      containing manure from the 30% WDGS diet. Sulfur content of manure increases with
      higher percentages of WDGS feed stock. Application method, diet, soil moisture
      content, and time since application should be considered when estimating VOC
      emissions. 

PMID- 25603070
TI  - Water quality and nitrogen mass loss from anaerobic lagoon columns receiving
      pretreated influent.
AB  - Control methods are needed to abate NH losses from swine anaerobic lagoons to
      reduce the contribution of confined swine operations to air pollution. In a 15-mo
      meso-scale column study, we evaluated the effect of manure pretreatment on water
      quality, reduction of N losses, and sludge accumulation in swine lagoons using
      (i) enhanced solid-liquid separation with polymer (SS) and (ii) solid-liquid
      separation plus biological N treatment using nitrification-denitrification (SS +
      NDN). A conventional anaerobic lagoon was included as a control. Concentrations
      of total Kjeldahl N (TKN), total ammoniacal N (TAN), and NO-N were monitored
      during the course of the study, and the volumes of column liquid and sludge were
      used to estimate N mass flows. At the end of the study, TKN and TAN
      concentrations in the liquid of SS columns were 35 and 37% lower than the
      control, respectively, and TKN and TAN concentrations in SS + NDN were 97 and 99%
      lower than the control. The N mass flow analysis revealed that SS reduced total N
      inflow by 30% and SS + NDN by 82% compared with the control. The SS was
      ineffective at reducing NH losses compared with the control. Instead, SS + NDN
      effectively reduced total NH losses by 50%, most of which occurred during the
      first 6 mo of the study. Although both pretreatments can stop the mass
      accumulation of total N in sludge, SS + NDN had the advantage of improving water
      quality and abating NH emissions from treated lagoons. As an additional
      environmental benefit, SS + NDN effluents could be used for crop irrigation
      without the risk of NH losses during land application. 

PMID- 25603071
TI  - Long-term environmental research: the upper washita river experimental
      watersheds, oklahoma, USA.
AB  - Water is central to life and earth processes, connecting physical, biological,
      chemical, ecological, and economic forces across the landscape. The vast scope of
      hydrologic sciences requires research efforts worldwide and across a wide range
      of disciplines. While hydrologic processes and scientific investigations related
      to sustainable agricultural systems are based on universal principles, research
      to understand processes and evaluate management practices is often site-specific
      to achieve a critical mass of expertise and research infrastructure to address
      spatially, temporally, and ecologically complex systems. In the face of dynamic
      climate, market, and policy environments, long-term research is required to
      understand and predict risks and possible outcomes of alternative scenarios. This
      special section describes the USDA-ARS's long-term research (1961 to present) in
      the Upper Washita River basin of Oklahoma. Data papers document datasets in
      detail (weather, hydrology, physiography, land cover, and sediment and nutrient
      water quality), and associated research papers present analyses based on those
      data. This living history of research is presented to engage collaborative
      scientists across institutions and disciplines to further explore complex,
      interactive processes and systems. Application of scientific understanding to
      resolve pressing challenges to agriculture while enhancing resilience of linked
      land and human systems will require complex research approaches. Research areas
      that this watershed research program continues to address include: resilience to
      current and future climate pressures; sources, fate, and transport of
      contaminants at a watershed scale; linked atmospheric-surface-subsurface
      hydrologic processes; high spatiotemporal resolution analyses of linked
      hydrologic processes; and multiple-objective decision making across linked farm
      to watershed scales. 

PMID- 25603072
TI  - Upper washita river experimental watersheds: meteorologic and soil climate
      measurement networks.
AB  - Hydrologic, watershed, water resources, and climate-related research conducted by
      the USDA-ARS Grazinglands Research Laboratory (GRL) are rooted in events dating
      back to the 1930s. In 1960, the 2927-km Southern Great Plains Research Watershed
      (SGPRW) was established to study the effectiveness of USDA flood control and soil
      erosion prevention programs. The size of the SGPRW was scaled back in 1978,
      leaving only the 610-km Little Washita River Experimental Watershed (LWREW) to be
      used as an outdoor hydrologic research laboratory. Since 1978, the number of
      measurement sites and types of instruments used to collect meteorologic and soil
      climate data have changed on the LWREW. Moreover, a second research watershed,
      the 786-km Fort Cobb Reservoir Experimental Watershed (FCREW), was added in 2004
      to the GRL's outdoor research laboratories to further study the effects of
      agricultural conservation practices on selected environmental endpoints. We
      describe the SGPREW, FCREW, and LWREW and the meteorologic measurement network
      (historic and present) deployed on them, provide descriptions of measurements,
      including information on accuracy and calibration, quality assurance measures
      (where known), and data archiving of the present network, give examples of data
      products and applications, and provide information for the public and research
      communities regarding access and availability of both the historic and recent
      data from these watersheds. 

PMID- 25603073
TI  - Upper washita river experimental watersheds: data screening procedure for data
      quality assurance.
AB  - The presence of non-stationary conditions in long-term hydrologic observation
      networks is associated with natural and anthropogenic stressors or network
      operation problems. Detection and identification of network operation drivers is
      fundamental in hydrologic investigation due to changes in systematic errors that
      can exacerbate modeling results or bias research conclusions. We applied a data
      screening procedure to the USDA-ARS experimental watersheds data sets () in
      Oklahoma. Detection of statistically significant monotonic trends and changes in
      mean and variance were used to investigate non-stationary conditions with network
      operation drivers to assess the impact of changes in the amount of systematic
      error. Detection of spurious data, filling in missing data, and data screening
      procedures were applied to >1000 time series, and processed data were made
      publicly available. The SPELLmap application was used for data processing and
      statistical tests on watershed segregated data sets and temporally aggregated
      data. A test for independency (Anderson test), normality, monotonic trend
      (Spearman test), detection of change point (Pettitt test), and split record test
      ( and -tests) were used to assess non-stationary conditions. Statistically
      significant (95% confidence limit) monotonic trends and changes in mean and
      variance were detected for annual maximum air temperature, rainfall, relative
      humidity, and solar radiation and in maximum and minimum soil temperature time
      series. Network operation procedures such as change in calibration protocols and
      sensor upgrades as well as natural regional weather trends were suspected as
      driving the detection of statistically significant trends and changes in mean and
      variance. We concluded that a data screening procedure that identifies changes in
      systematic errors and detection of false non-stationary conditions in hydrologic
      problems is fundamental before any modeling applications. 

PMID- 25603074
TI  - Upper washita river experimental watersheds: reservoir, groundwater, and stream
      flow data.
AB  - Surface and groundwater quantity and quality data are essential in many
      hydrologic applications and to the development of hydrologic and water quality
      simulation models. We describe the hydrologic data available in the Little
      Washita River Experimental Watershed (LWREW) of the Southern Great Plains
      Research Watershed (SGPRW) and Fort Cobb Reservoir Experimental Watershed
      (FCREW), both located in southwest Oklahoma. Specifically, we describe the flood
      retarding structures and corresponding stage, discharge, seepage, and consumptive
      use data (), stream gauges, and groundwater wells and their corresponding stream
      flow (; LWREW ARS 522-526 stream gauges) and groundwater level data (SGPRW
      groundwater levels data; LWREW groundwater data; ; ), respectively. Data
      collection is a collaborative effort between federal and state agencies. Stage,
      discharge, seepage, and consumptive use data for the Fort Cobb Reservoir are
      available from the Bureau of Reclamation and cover a period of 1959 to present.
      There are 15 stream gauges in the LWREW and six in the FCREW with varying data
      records. There were 479 observation wells with data in the SGPRW and 80 in the
      LWREW, with the latest records collected in 1992. In addition, groundwater level
      data are available from five real-time monitoring wells and 34 historical wells
      within the FCREW. These data sets have been used for several research
      applications. Plans for detailed groundwater data collection are underway to
      calibrate and validate the linked Soil and Water Assessment Tool (SWAT)-MODFLOW
      model. Also, plans are underway to conduct reservoir bathymetric surveys to
      determine the current reservoir capacity as affected by land use/land cover and
      overland and stream channel soil erosion. 

PMID- 25603075
TI  - Upper washita river experimental watersheds: sediment database.
AB  - One main objective for studying sediment in the Upper Washita River Experimental
      Watersheds was to improve the scientific understanding of the effectiveness of
      watershed conservation practices and floodwater-retardation structures in
      controlling floods and soil erosion in southwest Oklahoma. This paper summarizes
      the sediment data collection program in the watersheds during the 1961 to 2012
      time period. Gaging sites, record lengths, sampling procedures, data processing,
      and instrumentation are described. Examples of data use and analyses are
      presented to illustrate the potential use and relevance of the sediment data and
      to highlight past research findings. The sediment data, especially the breakpoint
      data from the unit source watersheds, are of great importance in understanding
      erosion processes, assessing the effectiveness of conservation practices, and
      evaluating and validating process-based soil erosion models. Data formats and
      availability are discussed, and the download URLs for accessing the data are
      specified. 

PMID- 25603076
TI  - Upper washita river experimental watersheds: nutrient water quality data.
AB  - Climate variability, changing land use and management, and dynamic policy
      environments are the main reasons why long-term research is needed to understand
      and predict possible water quality outcomes to alternative future scenarios. Long
      term water quality data sets are needed to address these water issues. Such data
      sets were acquired by the USDA-ARS in three watersheds in Oklahoma: the Southern
      Great Plains Research Watershed (SGPRW), the Little Washita River Experimental
      Watershed (LWREW), and the Fort Cobb Reservoir Experimental Watershed (FCREW). We
      provide: (i) a description of these water quality data sets, (ii) the sample
      collection and processing procedures used and an assessment of the data quality,
      (iii) summary analyses of the variability in each data set, and (iv) details
      about how to access these data sets. Water quality data collection in the SGPRW
      began in the 1960s and continued through 1978, while that in the LWREW covered
      the 1960s to 1990 period. Data collection began in the FCREW in 2004 and
      continues through the present. The data were collected from streams, unit source
      watersheds, groundwater wells, and reservoirs. The water quality data described
      for a given site are generally complete for a given period of record; however,
      not all sites were monitored continuously and were not necessarily analyzed for
      the same water quality parameters. These data sets are expected to improve
      modeling and assessments of conservation practices in relation to climate
      variability, land use changes, and other environmental factors and may be useful
      in developing strategies to mitigate these environmental impacts. 

PMID- 25603077
TI  - Upper washita river experimental watersheds: physiography data.
AB  - Physiographic data such as digital elevation models (DEMs), soils, geology,
      stream channel network characteristics, channel stability, and land use data are
      essential for understanding the complex hydrologic cycle and chemical transport
      processes of any given study area. We describe the physiographic data available
      in the Little Washita River Experimental Watershed (LWREW) and Fort Cobb
      Reservoir Experimental Watershed (FCREW) in Oklahoma. Specifically, we describe
      (i) available raw and post-processed DEM products (), (ii) available soils data (
      and ) and associated error analysis based on limited measured data, (iii)
      geologic formations in the LWREW and FCREW ( and ), and (iv) available rapid
      geomorphic assessment measurements () and their uses. Data collection is a
      collaborative effort among USGS, NRCS, and ARS. These data sets have been used
      for several research applications by USDA-ARS scientists and researchers from
      other institutions and agencies. Plans for detailed geomorphic assessment of
      stream channel networks in the FCREW are underway in collaboration with Oklahoma
      State University in Stillwater. The collected data will enable updating of the
      channel stability stage condition since there have been several major rainfall
      events in the watershed since the last geomorphic assessment. 

PMID- 25603078
TI  - Upper washita river experimental watersheds: land cover data sets (1974-2007) for
      two southwestern oklahoma agricultural watersheds.
AB  - Land cover data sets were developed for 1997, 1999, 2003, 2005, 2006, and 2007
      for the Little Washita River and Fort Cobb Reservoir experimental watersheds
      (LWREW and FCREW, respectively), located in southwestern Oklahoma, to support
      remote sensing based studies of soil water content. A previously unpublished
      retrospective land cover analysis covering the years 1974, 1981, 1985, 1989, and
      1994 was conducted to complement these data sets to gain a sense of the dynamics
      of land cover in both the LWREW and FCREW over the 33 yr. Each of these studies
      used satellite-based sensors of various spatial, radiometric, and spectral
      resolutions, but the number of images used, image date, and methods used to
      analyze the images varied from study to study. Our purpose was to document the
      details of the retrospective land cover study, to compare land cover between
      watersheds with time, and to compare findings from the various studies to
      elucidate changes or trends in land cover in each watershed during the 33 yr the
      data sets represent. Information on how to access to the data sets is also given.
      The LWREW was a grassland watershed that changed little during the study period.
      The FCREW was divided between grassland and cropland, but the cropland portion
      exhibited dynamic behavior that appeared correlated with peanut ( L.) price
      supports and Conservation Reserve programs. Dynamic land use information coupled
      with information concerning conservation practices will enhance assessment of
      conservation practice effectiveness as well as improve modeling of the fate and
      transport of chemicals and nutrients in watersheds. 

PMID- 25603079
TI  - Climate change and observed climate trends in the fort cobb experimental
      watershed.
AB  - Recurring droughts in the Southern Great Plains of the United States are
      stressing the landscape, increasing uncertainty and risk in agricultural
      production, and impeding optimal agronomic management of crop, pasture, and
      grazing systems. The distinct possibility that the severity of recent droughts
      may be related to a greenhouse-gas induced climate change introduces new
      challenges for water resources managers because the intensification of droughts
      could represent a permanent feature of the future climate. Climate records of the
      Fort Cobb watershed in central Oklahoma were analyzed to determine if recent
      decade-long trends in precipitation and air temperature were consistent with
      climate change projections for central Oklahoma. The historical precipitation
      record did not reveal any compelling evidence that the recent 20-yr-long decline
      in precipitation was related to climate change. Also, precipitation projections
      by global circulation models (GCMs) displayed a flat pattern through the end of
      the 21st century. Neither observed nor projected precipitation displayed a
      multidecadal monotonic rising or declining trend consistent with an ongoing
      warming climate. The recent trend in observed annual precipitation was probably a
      decade-scale variation not directly related to the warming climate. On the other
      hand, the observed monotonic warming trend of 0.34 degrees C decade that started
      around 1978 is consistent with GCM projections of increasing temperature for
      central Oklahoma. 

PMID- 25603080
TI  - Upper washita river experimental watersheds: multiyear stability of soil water
      content profiles.
AB  - Scaling in situ soil water content time series data to a large spatial domain is
      a key element of watershed environmental monitoring and modeling. The primary
      method of estimating and monitoring large-scale soil water content distributions
      is via in situ networks. It is critical to establish the stability of in situ
      networks when deploying them to study hydrologic systems. Two watersheds in
      Oklahoma, the Little Washita River Experimental Watershed (LWREW) and the Fort
      Cobb Reservoir Experimental Watershed (FCREW), are two prime examples of well
      equipped research watersheds that provide long-term measurements of atmospheric
      and soil water content from in situ networks. The soil water content measurement
      network on the LWREW has been in operation since 2002, with 20 stations available
      for investigating soil water dynamics at the watershed scale. Temporal stability
      analysis of the network is complicated by the changing configuration of the
      network, but it is possible to determine a singular long-term average for the
      network. The FCREW consists of 15 soil water content stations and began operation
      in 2007, providing detailed information across a mixed agricultural domain and
      was determined to be stable and representative of the region. This study
      reinforces the applicability of temporal stability analysis to very long time
      scales, which are now becoming available for soil moisture monitoring. Each of
      these networks is temporally stable with respect to soil water content at each
      depth on a spatial basis. The LWREW has a persistent pattern through the root
      zone profile, but the FCREW does not, which requires further investigation. 

PMID- 25603081
TI  - Seasonal sediment and nutrient transport patterns.
AB  - It is essential to understand sediment and nutrient sources and their spatial and
      temporal patterns to design effective mitigation strategies. However, long-term
      data sets to determine sediment and nutrient loadings are scarce and expensive to
      collect. The goal of this study was to determine seasonal patterns of suspended
      sediment (SS), total N (TN), and total P (TP) concentrations and loadings for
      three USGS gauge sites located at the Fort Cobb Reservoir Experimental watershed
      (FCREW) located in southwestern Oklahoma. Measured instantaneous discharge, SS,
      TN, and TP concentration data were used to develop lognormal water quality
      discharge relationships. The water quality-discharge relationships were used to
      generate estimated seasonal concentrations and loads based on hourly or 30-min
      interval discharge. The estimated concentrations and loads were used to determine
      seasonal patterns for SS, TN, and TP relative to the respective state water
      quality criteria. Decreasing and increasing monotonic trends were observed for
      the seasonal time series loads for all three sites, but they were insignificant
      based on the Spearman test (alpha = 0.05). The largest loads were estimated
      during the wet springs and summers. The study SS, TN, and TP target
      concentrations were exceeded in one season or another. The study results showed
      that the priority locations to implement the TN and TP conservation practices
      were the Lake Creek and Willow Creek subwatersheds during the winter and spring
      seasons. Common practices to mitigate nutrients and suspended sediments include
      nutrient management, no-till, conversion of cultivated land to pasture, riparian
      buffers, and animal exclusion. 

PMID- 25603082
TI  - Addition of straw or sawdust to mitigate greenhouse gas emissions from slurry
      produced by housed cattle: a field incubation study.
AB  - The use of housed wintering systems (e.g., barns) associated with dairy cattle
      farming is increasing in southern New Zealand. Typically, these wintering systems
      use straw or a woodmix as bedding material. Ammonia (NH) and greenhouse gas (GHG)
      emissions (nitrous oxide [NO] and methane [CH]) associated with storage of slurry
      + bedding material from wintering systems is poorly understood. A field
      incubation study was conducted to determine such emissions from stored slurry
      where bedding material (straw and sawdust) was added at two rates and stored for
      7 mo. During the first 4 mo of storage, compared with untreated slurry, the
      addition of sawdust significantly reduced NH and CH emissions from 29 to 3% of
      the initial slurry nitrogen (N) content and from 0.5 to <0.01% of the initial
      slurry carbon (C) content. However, sawdust enhanced NO emissions to 0.7% of the
      initial slurry-N content, compared with <0.01% for untreated slurry. Straw
      generally had an intermediate effect. Extending the storage period to 7 mo
      increased emissions from all treatments. Ammonia emissions were inversely related
      to the slurry C:N ratio and total solid (TS) content, and CH emissions were
      inversely related to slurry TS content. Mitigation of GHG emissions from stored
      slurry can be achieved by reducing the storage period as much as possible after
      winter slurry collection, providing ground conditions allow access for land
      spreading and nutrient inputs match pasture requirements. Although adding bedding
      material can reduce GHG emissions during storage, increased manure volumes for
      carting and spreading need to be considered. 

PMID- 25603083
TI  - A watershed modeling framework for phosphorus loading from residential and
      agricultural sources.
AB  - Phosphorus (P) loading from residential onsite wastewater systems (OWSs) into
      neighboring surface waters is a poorly understood process in rural watersheds;
      this can be further challenged when rural residential dwellings are intermixed
      with agricultural land use. The objectives of this research were (i) to design a
      P onsite wastewater simulator (POWSIM) to assess P loads from individual or
      clusters of residential OWSs typically used in Nova Scotia, Canada; and (ii) to
      simulate OWS P loads in a mixed agricultural watershed (Thomas Brook Watershed
      [TBW], NS) using the Soil and Water Assessment Tool (SWAT) model in conjunction
      with POWSIM, to predict and compare P loading from agricultural and residential
      sources. The POWSIM loading tool has three computational components: (i) disposal
      field selection and treatment media mass calculation, (ii) disposal field P
      treatment dynamics, and (iii) soil subsurface plume P treatment dynamics. The
      combination TBW POWSIM and SWAT modeling approach produced a better simulation of
      baseflow total P (TP) loads in both a predominantly residential subcatchment and
      one dominated by agriculture than the SWAT model without POWSIM. The residential
      subcatchment had 48% of its average annual land use TP load (simulated)
      contributed by OWSs, whereas the agricultural subcatchment had 39%. Watershed
      scale sensitivity analyses of POWSIM input parameters for 18- and 50-yr OWS
      operation periods found the P loading rate into the disposal field, long-term P
      removal rates in the disposal field and soil systems, soil maximum P sorption
      capacity, and mass of native soil involved in P treatment to be most sensitive. 

PMID- 25603084
TI  - Bayesian network for point and diffuse source phosphorus transfer from dairy
      pastures in South otago, new zealand.
AB  - Many factors affect the magnitude of nutrient losses from dairy farm systems.
      Bayesian Networks (BNs) are an alternative to conventional modeling that can
      evaluate complex multifactor problems using forward and backward reasoning. A BN
      of annual total phosphorus (TP) exports was developed for a hypothetical dairy
      farm in the south Otago region of New Zealand and was used to investigate and
      integrate the effects of different management options under contrasting rainfall
      and drainage regimes. Published literature was consulted to quantify the
      relationships that underpin the BN, with preference given to data and
      relationships derived from the Otago region. In its default state, the BN
      estimated loads of 0.34 +/- 0.42 kg TP ha for overland flow and 0.30 +/- 0.19 kg
      TP ha for subsurface flow, which are in line with reported TP losses in overland
      flow (0-1.1 kg TP ha) and in drainage (0.15-2.2 kg TP ha). Site attributes that
      cannot be managed, like annual rainfall and the average slope of the farm, were
      found to affect the loads of TP lost from dairy farms. The greatest loads (13.4
      kg TP ha) were predicted to occur with above-average annual rainfall (970 mm),
      where irrigation of farm dairy effluent was managed poorly, and where Olsen P
      concentrations were above pasture requirements (60 mg kg). Most of this loading
      was attributed to contributions from overland flow. This study demonstrates the
      value of using a BN to understand the complex interactions between site variables
      affecting P loss and their relative importance. 

PMID- 25603085
TI  - Evaluation of a Stepwise, Multiobjective, Multivariable Parameter Optimization
      Method for the APEX Model.
AB  - Hydrologic models are essential tools for environmental assessment of
      agricultural nonpoint-source pollution. The automatic calibration of hydrologic
      models, though efficient, demands significant computational power, limiting their
      application. The study objective was to develop and evaluate a stepwise,
      multiobjective, multivariable automatic calibration method for the Agricultural
      Environmental Policy eXtender (APEX) model for simulating runoff, sediment, total
      phosphorus (TP), and total nitrogen (TN). The most sensitive parameters were
      grouped according to the process they primarily affect (runoff, sediment
      transport, soil biological activity, TP transport, and TN transport) and were
      optimized separately and consecutively. Two multiobjective functions comprising
      combinations of coefficient of determination (), regression slope, and Nash
      Sutcliffe coefficient (NSC) and a global objective function, the Generalized
      Likelihood Uncertainty Estimation, were considered to select the optimal
      parameter combination. A previously manually calibrated and validated APEX model
      for three adjacent row-crop field-size watersheds in northeast Missouri was used
      as the baseline. The greatest improvements in model performance for sediment, TP,
      and TN, but not for runoff, were found after runoff parameter optimization,
      indicating that runoff parameter optimization was crucial for good simulation of
      sediment and nutrients. The values for sediment, TP, and TN improved from 0.59
      0.87 to 0.77-0.94. The NSC values for TP also improved after soil biological
      activity and TP parameter optimizations, but subsequent optimizations did not
      improve sediment or TN simulations. The objective function based on , slope, and
      NSC outperformed the other objective functions. Modelers can benefit from this
      cost-efficient optimization technique (2570 runs for 23 parameters). 

PMID- 25603086
TI  - Particle-facilitated transport of lindane in water-saturated tropical lateritic
      porous media.
AB  - The persistent insecticide lindane [(1alpha,2alpha,3beta,4alpha,5alpha,6beta)
      1,2,3,4,5,6-hexachlorocyclohexane] is still in use in many tropical countries and
      remains a threat to soil and water quality. We studied the sorption and transport
      of lindane onto and through lateritic soils in both the absence and presence of
      lignite particles, onto which lindane may preferably sorb. We determined a linear
      distribution coefficient of lindane onto the soil matrix of 3.38 +/- 0.16 L kg.
      Soil particles were not released from the porous medium on changing ionic
      strength, and also transport of lindane was not affected by changes in ionic
      strength. We fitted coupled transport models for lindane and the particles to the
      data, revealing that: (i) sorption kinetics of lindane onto the matrix is
      described best by intraparticle diffusion; (ii) 20% of the total porosity of the
      lateritic sample is intraparticle porosity; and (iii) only lignite particles with
      a median diameter <0.45 MUm were not retained in the porous medium and thus
      facilitated the transport of lindane. We conclude that although lindane and
      similar pollutants may sorb on tropical lateritic porous media, their transport
      may be facilitated by particles with high organic-C content or dissolved organic
      C (DOC). This may be of relevance in farmlands and swamp groundwater systems
      where DOC, produced by leaching or slow biodegradation of surface organic matter,
      could cause rapid groundwater contamination by sorbing pollutants. Moreover, the
      results of this study can help to understand nanoparticle behavior in lateritic
      soils as the size of particles that facilitate lindane transport approaches the
      nanoparticle size range. 

PMID- 25603087
TI  - Evaluation of long-term (1960-2010) groundwater fluoride contamination in Texas.
AB  - Groundwater quality degradation is a major threat to sustainable development in
      Texas. The aim of this study was to elucidate spatiotemporal patterns of
      groundwater fluoride (F) contamination in different water use classes in 16
      groundwater management areas in Texas between 1960 and 2010. Groundwater F
      concentration data were obtained from the Texas Water Development Board and
      aggregated over a decadal scale. Our results indicate that observations exceeding
      the drinking water quality threshold of World Health Organization (1.5 mg F L)
      and secondary maximum contaminant level (SMCL) (2 mg F L) of the USEPA increased
      from 26 and 19% in the 1960s to 37 and 23%, respectively, in the 2000s. In the
      2000s, F observations > SMCL among different water use classes followed the
      order: irrigation (39%) > domestic (20%) > public supply (17%). Extent and mode
      of interaction between F and other water quality parameters varied regionally. In
      western Texas, high F concentrations were prevalent at shallower depths (<50 m)
      and were positively correlated with bicarbonate (HCO) and sulfate anions. In
      contrast, in southern and southeastern Texas, higher F concentrations occurred at
      greater depths (>50 m) and were correlated with HCO and chloride anions. A
      spatial pattern has become apparent marked by "excess" F in western Texas
      groundwaters as compared with "inadequate" F contents in rest of the state.
      Groundwater F contamination in western Texas was largely influenced by
      groundwater mixing and evaporative enrichment as compared with water-rock
      interaction and mineral dissolution in the rest of the state. 

PMID- 25603088
TI  - Factors affecting arsenic and copper runoff from fields fertilized with poultry
      litter.
AB  - Arsenic (As) and copper (Cu) runoff from fields fertilized with poultry litter
      has received increasing attention in recent years, although it is not known if
      heavy metal runoff from poultry litter poses a significant threat to the
      environment. The objective of this study was to determine the main factors
      affecting As and Cu concentrations in runoff water from pastures receiving
      poultry litter applications. Rainfall simulation studies were conducted to
      determine the effects of the following treatments on metal runoff: (i) aluminum
      sulfate (alum) additions, (ii) diet modification using phytase or high available
      phosphorus corn, (iii) fertilizer type, (iv) poultry litter application rate, and
      (v) time until the first runoff event occurs after poultry litter application.
      Results showed that alum additions to poultry litter significantly decreased As
      and Cu concentrations in runoff water. Copper concentrations were highest in
      runoff from poultry litter from birds fed phytase diets compared with other
      diets; however, this effect may have been a result of wet storage conditions
      rather than diet. Triple superphosphate applications resulted in the lowest heavy
      metal concentrations in runoff water among all fertilizer treatments, while
      normal poultry litter resulted in the highest concentrations. Arsenic and Cu
      concentrations increased in runoff water as poultry litter application rates
      increased and decreased with increasing time until the first runoff event. These
      data indicate that adding alum to poultry litter, a cost-effective best
      management practice, which also results in lower P runoff and ammonia emissions,
      may also be an effective tool in reducing metal runoff. 

PMID- 25603089
TI  - Macroscopic assessment of nanosilver toxicity to soil denitrification kinetics.
AB  - A large increase in commercial and home use of silver nanoparticle (AgNP)
      products and technologies has raised concerns about their impact on environmental
      health. While several sources cite soils and sediments as the predominant sink
      for AgNPs in natural environments, few studies contribute to risk assessment of
      AgNPs in terrestrial environments. In this study, the effect of AgNPs ([Ag]: 1
      100 mg/kg, 15-50 nm with 0-90% polyvinylpyrrolidone [PVP] capping agent) on soil
      denitrification processes was investigated with batch kinetic experiments using
      well-characterized AgNPs. Although the effects on denitrification kinetics and
      equilibrium end-points were variable among the AgNPs, denitrification kinetics
      were limited under certain conditions (e.g., PVP-coated AgNPs >= 10 mg/kg). In
      assessing the impact of AgNPs on ecosystem processes, it is important to consider
      the interactions of AgNPs with soils and sediments in addition to the
      physicochemical properties (size, coating agents, sedimentation rate, solubility,
      surface charge properties, dispersibility) of AgNPs. 

PMID- 25603091
TI  - Subsidence Rates of Drained Agricultural Peatlands in New Zealand and the
      Relationship with Time since Drainage.
AB  - The drainage and conversion of peatlands to productive agro-ecosystems leads to
      ongoing surface subsidence because of densification (shrinkage and consolidation)
      and oxidation of the peat substrate. Knowing the ra0te of this surface subsidence
      is important for future land-use planning, carbon accounting, and economic
      analysis of drainage and pumping costs. We measured subsidence rates over the
      past decade at 119 sites across three large, agriculturally managed peatlands in
      the Waikato region, New Zealand. The average contemporary (2000s-2012) subsidence
      rate for Waikato peatlands was 19 +/- 2 mm yr (+/- SE) and was significantly less
      ( = 0.01) than the historic rate of 26 +/- 1 mm yr between the 1920s and 2000s. A
      reduction in the rate of subsidence through time was attributed to the transition
      from rapid initial consolidation and shrinkage to slower, long-term, ongoing
      oxidation. These subsidence rates agree well with a literature synthesis of
      temperate zone subsidence rates reported for similar lengths of time since
      drainage. A strong nonlinear relationship was found between temperate zone
      subsidence rates and time since initial peatland drainage: Subsidence (mm yr) =
      226 * (years since drained) ( = 0.88). This relationship suggests that time since
      drainage exerts strong control over the rate of peatland subsidence and that
      ongoing peatland subsidence rates can be predicted to gradually decline with time
      in the absence of major land disturbance. 

PMID- 25603090
TI  - Long-term impact of tillage practices and phosphorus fertilization on soil
      phosphorus forms as determined by p nuclear magnetic resonance spectroscopy.
AB  - Conservation tillage practices have become increasingly common in recent years to
      reduce soil erosion, improve water conservation, and increase soil organic
      matter. Research suggests that conservation tillage can stratify soil test
      phosphorus (P), but little is known about the effects on soil organic P. This
      study was conducted to assess the long-term effects of tillage practices (no-till
      [NT] and mouldboard plowing) and P fertilization (0 and 35 kg P ha) on the
      distribution of P species in the soil profile. Soil samples from a long-term corn
      soybean rotation experiment in Quebec, Canada, were collected from three depths
      (0-5, 5-10, and 10-20 cm). These samples were analyzed for total P (TP), total C
      (TC), total N (TN), pH, and Mehlich-3 P (PM3); P forms were characterized with
      solution phosphorus-31 nuclear magnetic resonance spectroscopy (P-NMR). Results
      showed a stratification of TP, TC, TN, pH, PM3, and Mehlich-3-extractable
      aluminum and magnesium under NT management. The PM3 and orthophosphate
      concentrations were greater at the soil surface (0-5 cm) of the NT-P (soil
      treatment with 35 kg P ha) treatment. Organic P forms (orthophosphate monoesters,
      especially -IP, and nucleotides) had accumulated in the deep layer of NT
      treatment possibly due to preferential movement. We found evidence that the NT
      system and P fertilization changed the distribution of P forms along the soil
      profile, potentially increasing soluble inorganic P loss in surface runoff and
      organic P in drainage and decreasing bioavailability of inorganic and organic P
      in deeper soil layers. 

PMID- 25603092
TI  - Atrazine soil core residue analysis from an agricultural field 21 years after its
      ban.
AB  - Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) groundwater
      monitoring in the Zwischenscholle aquifer in western Germany revealed
      concentrations exceeding the threshold value of 0.1 MUg L and increasing
      concentration trends even 20 yr after its ban. Accordingly, the hypothesis was
      raised that a continued release of bound atrazine residues from the soil into the
      Zwischenscholle aquifer in combination with the low atrazine degradation in
      groundwater contributes to elevated atrazine in groundwater. Three soil cores
      reaching down to the groundwater table were taken from an agricultural field
      where atrazine had been applied before its ban in 1991. Atrazine residues were
      extracted from eight soil layers down to 300 cm using accelerated solvent
      extraction and analyzed using liquid chromatography-tandem mass spectrometry.
      Extracted atrazine concentrations ranged between 0.2 and 0.01 MUg kg for topsoil
      and subsoil, respectively. The extracted mass from the soil profiles represented
      0.07% of the applied mass, with 0.01% remaining in the top layer. A complete and
      instantaneous remobilization of atrazine residues and vertical mixing with the
      groundwater body below would lead to atrazine groundwater concentrations of 0.068
      MUg L. Considering the area where atrazine was applied in the region and assuming
      instantaneous lateral mixing in the Zwischenscholle aquifer would result in a
      mean groundwater concentration of 0.002 MUg L. A conservative estimation suggests
      an atrazine half-life value of about 2 yr for the soil zone, which significantly
      exceeds highest atrazine half-lives found in the literature (433 d for subsurface
      soils). The long-term environmental behavior of atrazine and its metabolites thus
      needs to be reconsidered. 

PMID- 25603094
TI  - Variation in riverine nitrate flux and fall nitrogen fertilizer application in
      East-central illinois.
AB  - In east-central Illinois, fertilizer sales during the past 20 yr suggest that
      approximately half of the fertilizer nitrogen (N) applied to corn ( L.) occurs in
      the fall; however, fall fertilizer N sales were greatly reduced in 2009 as wet
      soil conditions restricted fall fieldwork, including fertilizer N applications.
      In 2010, we observed unusually low flow-weighted nitrate concentrations
      (approximately 40% below the long-term average) in two east-central Illinois
      rivers (5.7 mg N L in the Embarras River and 5.6 mg N L in the Lake Fork of the
      Kaskaskia River). Using long-term river nitrate data sets (1993-2012 for the
      Embarras and 1997-2012 for the Kaskaskia), we examined nitrate concentrations and
      developed regression models to estimate the association between fall fertilizer N
      application on riverine nitrate yields in these tile-drained watersheds. During
      these periods of record, annual riverine nitrate yields ranged from 8 to 57 kg N
      ha yr (30 kg N ha yr average) for the Embarras River and 2.6 to 59 kg N ha yr (32
      kg N ha yr average) for the Kaskaskia. Multivariate linear regression
      relationships with the current and previous year's annual water yields, previous
      year's corn yield, and nine-county fall fertilizer sales accounted for 96% of the
      annual variation in nitrate yield in both watersheds. Running the regression
      models with fall fertilizer sales set to the 2009 amount suggests that the
      average reduction in nitrate yield (for the period of record) would be 17 and 20%
      for the Embarras and Kaskaskia Rivers, respectively. These data suggest that
      shifting fertilizer N application to the spring can be detected in watersheds as
      large as 481 km. 

PMID- 25603093
TI  - High ozone increases soil perchlorate but does not affect foliar perchlorate
      content.
AB  - Ozone (O) is implicated in the natural source inventory of ClO, a hydrophilic
      salt that migrates to groundwater and interferes with the uptake of iodide in
      mammals, including humans. Tropospheric O is elevated in many urban and some
      rural areas in the United States and globally. We previously showed that
      controlled O exposure at near-ambient concentrations (up to 114 nL L, 12-h mean)
      did not increase foliar ClO. Under laboratory conditions, O has been shown to
      oxidize Cl to ClO. Plant tissues contain Cl and exhibit responses to O invoking
      redox reactions. As higher levels of O are associated with stratospheric
      incursion and with developing megacities, we have hypothesized that exposure of
      vegetation to such elevated O may increase foliar ClO. This would contribute to
      ClO in environments without obvious point sources. At these high O concentrations
      (up to 204 nL L, 12-h mean; 320 nL L maximum), we demonstrated an increase in the
      ClO concentration in surface soil that was linearly related to the O
      concentration. There was no relationship of foliar ClO with O exposure or dose
      (stomatal uptake). Accumulation of ClO varied among species at low O, but this
      was not related to soil surface ClO or to foliar ClO concentrations following
      exposure to O. These data extend our previous conclusions to the highest levels
      of plausible O exposure, that tropospheric O contributes to environmental ClO
      through interaction with the soil but not through increased foliar ClO. 

PMID- 25603095
TI  - Climate change and land use drivers of fecal bacteria in tropical hawaiian
      rivers.
AB  - Potential shifts in rainfall driven by climate change are anticipated to affect
      watershed processes (e.g., soil moisture, runoff, stream flow), yet few model
      systems exist in the tropics to test hypotheses about how these processes may
      respond to these shifts. We used a sequence of nine watersheds on Hawaii Island
      spanning 3000 mm (7500-4500 mm) of mean annual rainfall (MAR) to investigate the
      effects of short-term (24-h) and long-term (MAR) rainfall on three fecal
      indicator bacteria (FIB) (enterococci, total coliforms, and ). All sample sites
      were in native Ohia dominated forest above 600 m in elevation. Additional samples
      were collected just above sea level where the predominant land cover is pasture
      and agriculture, permitting the additional study of interactions between land use
      across the MAR gradient. We found that declines in MAR significantly amplified
      concentrations of all three FIB and that FIB yield increased more rapidly with 24
      h rainfall in low-MAR watersheds than in high-MAR watersheds. Because storm
      frequency decreases with declining MAR, the rate of change in water potential
      affects microbial growth, whereas increased rainfall intensity dislodges more
      soil and bacteria as runoff compared with water-logged soils of high-MAR
      watersheds. As expected, declines in % forest cover and increased urbanization
      increased FIB. Taken together, shifts in rainfall may alter bacterial inputs to
      tropical streams, with land use change also affecting water quality in streams
      and near-shore environments. 

PMID- 25603096
TI  - Transport and persistence of tylosin-resistant enterococci, genes, and tylosin in
      soil and drainage water from fields receiving Swine manure.
AB  - Land application of manure from tylosin-treated swine introduces tylosin, tylosin
      resistant enterococci, and erythromycin resistant rRNA methylase () genes, which
      confer resistance to tylosin. This study documents the persistence and transport
      of tylosin-resistant enterococci, genes, and tylosin in tile-drained chisel plow
      and no-till agricultural fields treated with liquid swine manure in alternating
      years. Between 70 and 100% of the enterococci in manure were resistant to tylosin
      and B concentrations exceeded 10 copies g manure, while the mean F concentrations
      exceeded 10 copies g manure (T was not detected). The mean concentration of
      tylosin was 73 ng g manure. Soil collected from the manure injection band closely
      following application contained >10 copies g soil of both B and F in 2010 and >10
      copies g soil after the 2011 application compared to 3 * 10 to 3 * 10 copies g
      soil in the no-manure control plots. Gene abundances declined over the subsequent
      2-yr period to levels similar to those in the no-manure controls. Concentrations
      of enterococci in tile water were low, while tylosin-resistant enterococci were
      rarely detected. In approximately 75% of tile water samples, B was detected, and
      F was detected in 30% of tile water samples, but levels of these genes were not
      elevated due to manure application, and no difference was found between tillage
      practices. These results show that tylosin usage increased the short-term
      occurrence of tylosin-resistant enterococci, genes, and tylosin in soils but had
      minimal effect on tile drainage water quality in years of average to below
      average precipitation. 

PMID- 25603097
TI  - Antecedent moisture controls on stream nitrate flux in an agricultural watershed.
AB  - Evaluating nitrate-N fluxes from agricultural landscapes is inherently complex
      due to the wide range of intrinsic and dynamic controlling variables. In this
      study, we investigate the influence of contrasting antecedent moisture conditions
      on nitrate-N flux magnitude and dynamics in a single agricultural watershed on
      intra-annual and rainfall-event temporal scales. High temporal resolution
      discharge and nitrate concentration data were collected to evaluate nitrate-N
      flux magnitude associated with wet (2009) and dry (2012) conditions. Analysis of
      individual rainfall events revealed a marked and consistent difference in nitrate
      N flux response attributed to wet/dry cycles. Large-magnitude dilutions (up to 10
      mg N L) persisted during the wet antecedent conditions (2009), consistent with a
      dominant baseflow contribution and excess groundwater release in relation to
      precipitation volume (discharge > > precipitation). Smaller-magnitude
      concentrations (<7 mg N L) were observed during the drought conditions of 2012,
      consistent with a quickflow-dominated response to rain events and
      infiltration/storage of precipitation resulting in discharge < precipitation.
      Nitrate-N loads and yields from the watershed were much higher (up to an order of
      magnitude) in the wet year vs. the dry year. Our results suggest that the
      response of nitrate-N loading to rain events is highly dependent on intra-annual
      antecedent moisture conditions and subsurface hydrologic connectivity, which
      together dictate the dominant hydrologic pathways for stream recharge.
      Additionally, the results of our study indicate that continued pronounced wet/dry
      cycles may become more dominant as the short-term driver of future nitrate-N
      exports. 

PMID- 25603098
TI  - Phosphorus release from dairy manure, the manure-derived biochar, and their
      amended soil: effects of phosphorus nature and soil property.
AB  - Land application of animal manure often risks excessive phosphorus (P) release
      into the surrounding water. The aim of this study was to convert the dairy manure
      into biochar, followed by their application into soil, and then to investigate P
      release from the manure and its derived biochar as well as from the manure- and
      biochar-amended soil. The results showed that P release was reduced when the
      manure was converted into biochar due to formation of less-soluble whitlockite
      [(Ca, Mg)(PO)]. The cumulative P released from biochar over 240 h was 0.26 g kg,
      a 76% reduction of that from the manure (1.07 g kg). The kinetic release of P
      from the manure was determined by the fast desorption process and was better
      fitted to Elovich equation, whereas P release from biochar was initially
      controlled by the diffusion process and then by slow but steady dissolution of
      (Ca,Mg)(PO), following the parabolic diffusion and linear models, respectively.
      When the manure or biochar was incorporated into the soil, P release in the CaCl
      and simulated acid rain water extraction from biochar-amended soil was
      consistently lower than that from the manure-amended soil during 210-d
      incubation. The lower P release in the biochar-amended soil was determined by
      stable P form (Ca, Mg)(PO) in the biochar itself, but less from the soil property
      effect. Results indicated that initial high P release from manure can be
      mitigated by converting the manure into biochar. 

PMID- 25603099
TI  - Dry mature fine tailings as oil sands reclamation substrates for three native
      grasses.
AB  - Mature fine tailings (MFT) are a by-product of oil sands mining that must be
      reclaimed through capping or use as a reclamation substrate. Some chemical and
      physical properties of MFT make it inhospitable for plant growth, such as high
      concentrations of sodium, sulfate, chloride, and hydrocarbons. A greenhouse study
      assessed whether substrates of various mixes of dry MFT, overburden sand, and
      peat mineral soil mix (PMM) and caps of forest floor organic material (LFH) and
      PMM would support the emergence and growth of three native grass species commonly
      used in land reclamation. Select vegetation properties were monitored for 16 wk
      in the greenhouse; select chemical and physical substrate properties were
      determined in the laboratory. was more tolerant of dry MFT than and . Mean
      aboveground and belowground biomass were more than twice as high on substrates
      with <60% MFT than on 100% MFT. Aboveground biomass was two to four times greater
      with capping than without and 30% greater on LFH than PMM caps. Cover and density
      followed similar trends. Belowground biomass on capped substrates was at least
      double that on uncapped substrates. Aboveground biomass was almost doubled with
      the use of fertilizer. High concentrations of hydrocarbons and exchangeable ions
      were associated with reduced plant growth and health. Results from this study
      show that capping, amendments, and fertilizer may improve the reclamation
      potential of dry MFT. 

PMID- 25603101
TI  - Association of leishmaniasis with TNF alpha promoter and SLC11A1 gene
      polymorphisms in patients of two endemic areas in Mexico.
AB  - Some Single Nucleotide Polymorphisms (SNPs) of interleukins and other modulatory
      molecules of the immune response play an important role in susceptibility to
      infectious diseases, particularly those involving intracellular parasites. In
      this study, we evaluated allele, genotype and haplotype associations of two SNPs
      of the TNF-alpha promoter and seven of the SLC11A1 gene in 79 patients with
      localized cutaneous leishmaniasis (CL) and 15 with visceral leishmaniasis (VL),
      compared with 127 and 89 locality paired controls, respectively, from two endemic
      areas of Chiapas State, Mexico. None of the TNF-alpha alleles and genotypes was
      associated either to CL or to VL. Alleles rs2276631-C (P = 0.02; OR [95%CI] =
      2.11 [1.16-3.86]) and rs2279015-G (P = 0.005; OR [95%CI] = 2.42 [1.33-4.41]) of
      SLC11A1, were associated with susceptibility to VL, whereas genotypes rs2276631
      C/C (P = 0.003; OR [95%CI] = 2.65 [1.41-5.00]) and rs2279015 G/G (P = 0.018; OR
      [95%CI] = 2.05 [1.15-3.64]) were significantly increased in CL and VL patients,
      respectively. Complete haplotypes involved in susceptibility were CGCCGDins with
      VL and CGCCADins with CL. CGCCA was the minimal susceptibility haplotype for CL
      and CCG for VL. Our data suggest that SLC11A1 gene polymorphisms might have a
      relevant role in the pathology of leishmaniasis, directing towards susceptibility
      outcome of this disease in residents of an endemic area.

PMID- 25603102
TI  - (Ubi)quitin' the h2bit: recent insights into the roles of H2B ubiquitylation in
      DNA replication and transcription.
AB  - The reversible ubiquitylation of histone H2B has long been known to regulate gene
      transcription, and is now understood to modulate DNA replication as well. In this
      review, we describe how recent, genome-wide analyses have demonstrated that this
      histone mark has further reaching effects on transcription and replication than
      once thought. We also consider the ongoing efforts to elucidate the molecular
      mechanisms by which H2B ubiquitylation affects processes on the DNA template, and
      outline the various hypothetical scenarios. 

PMID- 25603103
TI  - Evaluation of surgical freedom for microscopic and endoscopic transsphenoidal
      approaches to the sella.
AB  - BACKGROUND: Microscopic and endoscopic transsphenoidal approaches to the sellar
      are well established. Surgical freedom is an important skull base principle that
      can be measured objectively and used to compare approaches. OBJECTIVE: To compare
      the surgical freedom of 4 transsphenoidal approaches to the sella turcica to aid
      in surgical approach selection. METHODS: Four transsphenoidal approaches to the
      sella were performed on 8 silicon-injected cadaveric heads. Surgical freedom was
      determined with stereotactic image guidance using previously established
      techniques. The results are presented as the area of surgical freedom and angular
      surgical freedom (angle of attack) in the axial and sagittal planes. RESULTS:
      Mean total exposed area surgical freedom for the microscopic sublabial,
      endoscopic binostril, endoscopic uninostril, and microscopic endonasal approaches
      were 102 +/- 13, 89 +/- 6, 81 +/- 4, and 69 +/- 10 cm2, respectively. The
      endoscopic binostril approach had the greatest surgical freedom at the pituitary
      gland and ipsilateral and contralateral internal carotid arteries (25.7 +/- 5.4,
      28.0 +/- 4.0, and 23.0 +/- 3.0 cm2) compared with the microscopic sublabial (21.8
      +/- 3.5, 21.3 +/- 2.4, and 19.5 +/- 6.3 cm2), microscopic endonasal (14.2 +/-
      2.7, 14.1 +/- 3.2, and 16.3 +/- 4.0 cm2), and endoscopic uninostril (19.7 +/-
      4.8, 22.4 +/- 2.3, and 19.5 +/- 2.9 cm2) approaches. Axial angle of attack was
      greatest for the microscopic sublabial approach to the same targets (14.7 +/- 1.3
      degrees , 11.0 +/- 1.5 degrees , and 11.8 +/- 1.1 degrees ). For the sagittal
      angle of attack, the endoscopic binostril approach was superior for all 3 targets
      (16.6 +/- 1.7 degrees , 17.2 +/- 0.70 degrees , and 15.5 +/- 1.2 degrees ).
      CONCLUSION: Microscopic sublabial and endoscopic binostril approaches provided
      superior surgical freedom compared with the endonasal microscopic and uninostril
      endoscopic approaches. This work provides objective baseline values for the
      quantification and evaluation of future refinements in surgical technique or
      instrumentation.

PMID- 25603104
TI  - Insurance status influences the rates of reportable quality metrics in brain
      tumor patients: a nationwide inpatient sample study.
AB  - BACKGROUND: In 2010, the Patient Protection and Affordable Care Act was passed to
      expand health insurance, narrow health care disparities, and improve health care
      quality in the United States. As part of this initiative, the Agency for
      Healthcare Research and Quality and the Centers for Medicare and Medicaid
      Services are now tracking quality metrics. OBJECTIVE: To analyze the effects of
      insurance on the incidence of patient safety indicators (PSIs) and hospital
      acquired conditions (HACs) using the Nationwide Inpatient Sample for patients who
      have brain tumors. METHODS: The Nationwide Inpatient Sample was queried for all
      hospitalizations between 2002 and 2011 involving patients with brain tumors.
      Because of the confounding age restriction with Medicare, comparisons were made
      between Medicaid/self-pay and private insurance. To determine which factors
      contributed to HACs and PSIs, odds ratios were calculated for each risk factor.
      Logistic regression models were used to assess the effect of payer status on
      individual PSIs, HACs, and patient outcomes. RESULTS: Medicaid/self-pay patients
      had a higher PSI and HAC incidence compared with private insurance patients. The
      greater incidence of PSIs and HACs correlated with increased length of stay,
      worse discharge outcomes, and increased in-hospital mortality. CONCLUSION:
      Variability exists in the incidence of PSIs and HACs in patients with brain
      tumors based on insurance status. Controlling for both patient and hospital
      factors can explain these differences. The cause of these disparities should be
      studied prospectively to begin the process of improving quality metrics in
      vulnerable patient populations.

PMID- 25603105
TI  - Endoscopically assisted piriformis-to-knee surgery of sciatic, peroneal, and
      tibial nerves: technical note.
AB  - BACKGROUND: Proximal lesions of the sciatic nerve are often difficult to diagnose
      and to treat properly. In particular, if there are posttraumatic or postoperative
      alterations, imaging might not identify the level and location of lesion. Due to
      the sciatic nerve anatomy, the same is true for clinical and electrophysiological
      evaluation with a risk of delayed surgery and, thus, unsuccessful surgery.
      Therefore, in some unclear cases, surgical exploration of the whole sciatic nerve
      and its divisions could be the only means to determine the correct diagnosis and
      allow prompt treatment to produce the best clinical outcome. OBJECTIVE: To
      describe a novel minimally invasive technique to explore and treat patients with
      proximal sciatic, peroneal, and tibial nerve lesions. Intraoperative findings,
      surgical considerations, and complications are presented. METHODS: From January
      2012 to November 2013, 9 consecutive patients with lesions of the sciatic,
      peroneal, and tibial nerves underwent endoscopy and were treated. The technical
      considerations of these cases are presented with regard to the retrospectively
      collected clinical and surgical data to evaluate the pros and cons of the
      technique. RESULTS: A subgluteal incision, as the primary endoscopic port, was
      used in all 9 patients. An additional mid-thigh and fibular head incision was
      thought necessary in 3 patients. An extension of the approach by a secondary
      transgluteal incision was performed in 4 patients. In 2 of these sciatic lesions,
      autologous nerve grafts were placed. One perineurioma was detected and
      bioptically secured. There were no complications. Six patients experienced pain
      relief; in 6, we observed motor improvement. The mean follow-up was 9.5 months.
      CONCLUSION: The endoscopically assisted single- to multiportal sciatic
      exploration technique provides excellent visualization that enables nerve
      inspection, lesion detection, and decompression, and obviates the need for more
      extensive approaches in cases of unclear sciatic nerve pathology. By adding
      several ports, whole-length exploration of the sciatic from the notch to fibular
      head level is feasible.

PMID- 25603106
TI  - Computed tomography-based image-guided system in spinal surgery: state of the art
      through 10 years of experience.
AB  - BACKGROUND: Image-guided navigation systems (IGS) grant excellent clinical and
      radiological results, minimizing risks correlated with spinal instrumentation.
      However, there is some concern regarding the real need for IGS and its
      indications. OBJECTIVE: To analyze the accuracy, technical aspect, and radiation
      exposure data of the principal IGS based on computed tomography (CT) imaging.
      METHODS: The data of all patients treated for spinal instrumentation with the aid
      of an IGS system from January 2003 to March 2013 were retrospectively analyzed.
      We defined 2 groups: group I with an IGS system based on a preoperative CT scan;
      group II relied on an intraoperative CT scan. Screw accuracy was assessed with a
      postoperative CT scan control. Radiation dosage for patients was defined by using
      the technical parameters and dose report data. Statistical analysis was performed
      using the Fisher exact test with a significance of 5% (P value < .05). RESULTS:
      Two thousand twenty patients and 11,144 screws were analyzed. Group I had 794
      patients (4246 screws); the accuracy was 96.1%. Group II had 1226 patients (6898
      screws) treated, with 98.5% accuracy (P = .001). The radiation dose analysis
      showed better results in group II, with significant reduction of the effective
      dose to the patient. CONCLUSION: The IGS based on an intraoperative CT scan
      grants excellent results, eliminating the rate of reoperation for misplaced
      instrumentations (screws, plate, and cage) or for inadequate bone decompression.
      However, this technology cannot replace the surgical skills, experience, and
      knowledge necessary for spine surgery.

PMID- 25603108
TI  - Impact of body mass index on adjacent segment disease after lumbar fusion for
      degenerative spine disease.
AB  - BACKGROUND: Adjacent segment disease is an important complication after fusion of
      degenerative lumbar spines. However, the role of body mass index (BMI) in
      adjacent segment disease has been addressed less. OBJECTIVE: To examine the
      relationship between BMI and adjacent segment disease after lumbar fusion for
      degenerative spine diseases. METHODS: For this retrospective study, we enrolled
      190 patients undergoing lumbar fusion surgery for degeneration. BMI at admission
      was documented. Adjacent segment disease was defined by integration of the
      clinical presentations and radiographic criteria based on the morphology of the
      dural sac on magnetic resonance images. RESULTS: Adjacent segment disease was
      identified in 13 of the 190 patients, accounting for 6.8%. The interval between
      surgery and diagnosis as adjacent segment disease ranged from 21 to 66 months.
      Five of the 13 patients required subsequent surgical intervention for clinically
      relevant adjacent segment disease. In the logistic regression model, BMI was a
      risk factor for adjacent segment disease after lumbar fusion for degenerative
      spine diseases (odds ratio, 1.68; 95% confidence interval, 1.27-2.21; P < .001).
      Any increase of 1 mean value in BMI would increase the adjacent segment disease
      rate by 67.6%. The patients were subdivided into 2 groups based on BMI, and up to
      11.9% of patients with BMI >= 25 kg/m were diagnosed as having adjacent segment
      disease at the last follow-up. CONCLUSION: BMI is a risk factor for adjacent
      segment disease in patients undergoing lumbar fusion for degenerative spine
      diseases. Because BMI is clinically objective and modifiable, controlling body
      weight before or after surgery may provide opportunities to reduce the rate of
      adjacent segment disease and to improve the outcome of fusion surgery.

PMID- 25603107
TI  - Pediatric low-grade ganglioglioma: epidemiology, treatments, and outcome analysis
      on 348 children from the surveillance, epidemiology, and end results database.
AB  - BACKGROUND: Low-grade gangliogliomas/gangliocytomas (GGs) are rare tumors of the
      central nervous system that occur mostly in young people. Because of their
      rarity, large-scale, population-based studies focusing on epidemiology and
      outcomes are lacking. OBJECTIVE: To use the Surveillance, Epidemiology, and End
      Results (SEER) data sets of the National Cancer Institute to study demographics,
      tumor location, initial treatment, and outcome data on low-grade GGs in children.
      METHODS: SEER-STAT v8.1.2 identified all patients aged 0 to 19 years in the SEER
      data sets with low-grade GGs. Using the Kaplan-Meier method and Cox proportional
      hazard regression, we examined associations between these characteristics and
      survival. RESULTS: There were 348 children with low-grade GGs diagnosed from 2004
      to 2010, with a median follow-up of 37 months. Tumors were more prevalent in
      males (n = 208, 59.8%) than females (n = 140, 40.2%) (P < .001). Almost 63%
      occurred in children >10 years, whereas only 3.5% were found in those <1 year
      old. Approximately 50% were located in the temporal lobes, and only 3.7% and 3.5%
      were located in the brainstem and spinal cord, respectively. Surgery was
      performed on 91.6% of cases, with gross total resection achieved in 68.3%.
      Radiation was used in 3.2%. Young age (<1 year) and brainstem location were
      associated with worse overall survival. CONCLUSION: This study shows that low
      grade GGs occur in older children with a male preference. Gross total resection
      is achieved in the majority of cases, and radiation is rarely used. Although the
      majority of patients have an excellent prognosis, infants and patients with
      brainstem tumors have worse survival rates.

PMID- 25603109
TI  - Surgical management of ruptured middle cerebral artery aneurysms with large
      intraparenchymal or sylvian fissure hematomas.
AB  - BACKGROUND: Craniotomy for hematoma evacuation and aneurysm clipping is the
      treatment modality of choice for ruptured middle cerebral artery (MCA) aneurysms
      with intracranial hematomas. Recent literature suggests that endovascular coil
      embolization followed by hematoma evacuation can be an acceptable alternative.
      OBJECTIVE: To determine neurological outcomes in patients with ruptured MCA
      aneurysms and intraparenchymal or sylvian fissure hematomas. METHODS: The records
      of 49 patients with ruptured MCA aneurysms with large intracranial hematomas
      treated with hematoma evacuation and aneurysm clipping between January 2000 and
      December 2013 were retrospectively reviewed. RESULTS: Within this cohort, 35
      patients (71.4%) were Hunt and Hess grade IV or V on presentation. The mean
      hematoma volume was 100.4 +/- 77.2 mL. Craniectomy was performed in 40 patients
      (81.6%). Angiographic vasospasm developed in 15 patients (30.6%). The in-hospital
      mortality rate was 28.6% (14 patients). At a mean of 25.3 +/- 34.0 months follow
      up, a good outcome (modified Rankin Scale [mRS] score 0-3) was observed in 18
      patients (36.7%). Significant factors associated with poor outcome or death (mRS
      scores of 4-6) included increasing age (P < .01), increasing Hunt and Hess grade
      (P = .03), increasing modified Fisher grade (P = .01), presence of
      intraventricular hemorrhage (P < .01), decreasing percentage of hematoma
      evacuation (P < .05), need for craniectomy (P <. 01), need for external
      ventricular drainage (P = .04), and angiographic vasospasm (P = .02). CONCLUSION:
      MCA aneurysm rupture with concomitant large intraparenchymal or sylvian fissure
      hematoma formation carries a grave prognosis. Simultaneous hematoma evacuation
      and aneurysm clipping with or without craniectomy can be an effective treatment
      modality.

PMID- 25603110
TI  - Usefulness of cordotomy in patients with cancer who experience bilateral pain:
      implications of increased pain and new pain.
AB  - BACKGROUND: Although mirror pain occurs after cordotomy in patients experiencing
      unilateral pain via a referred pain mechanism, no studies have examined whether
      this pain mechanism operates in patients who have bilateral pain. OBJECTIVE: To
      assess the usefulness of cordotomy for bilateral pain from the viewpoint of
      increased pain or new pain caused by a referred pain mechanism. METHODS: Twenty
      six patients who underwent percutaneous cordotomy through C1-C2 for severe
      bilateral cancer pain in the lumbosacral nerve region were enrolled. Pain was
      dominant on 1 side in 23 patients, and pain was equally severe on both sides in 3
      patients. Unilateral cordotomy was performed for the dominant side of pain, and
      bilateral cordotomy was performed for 13 patients in whom pain on the nondominant
      side developed or remained severe after cordotomy. RESULTS: After unilateral
      cordotomy, 19 patients (73.1%) exhibited increased pain, which for 14 patients
      was as severe as the original dominant pain. After bilateral cordotomy, 7
      patients (53.4%) exhibited new pain, which was located cephalad to the region
      rendered analgesic by cordotomy and was better controlled than the original pain.
      No pathological organic causes of new pain were found in any patient, and
      evidence of a referred pain mechanism was found in 3 patients after bilateral
      cordotomy. CONCLUSION: These results show that a referred pain mechanism causes
      increased or new pain after cordotomy in patients with bilateral pain.
      Nevertheless, cordotomy can still be indicated for patients with bilateral pain
      because postoperative pain is better controlled than the original pain.

PMID- 25603111
TI  - Letter: malignant craniopharyngioma and radiotherapy: the missing link.

PMID- 25603112
TI  - In reply: facetal orientation in congenital atlantoaxial dislocation: there are
      angles and there are "angles".

PMID- 25603114
TI  - Revealing letters in rolled Herculaneum papyri by X-ray phase-contrast imaging.
AB  - Hundreds of papyrus rolls, buried by the eruption of Mount Vesuvius in 79 AD and
      belonging to the only library passed on from Antiquity, were discovered 260 years
      ago at Herculaneum. These carbonized papyri are extremely fragile and are
      inevitably damaged or destroyed in the process of trying to open them to read
      their contents. In recent years, new imaging techniques have been developed to
      read the texts without unwrapping the rolls. Until now, specialists have been
      unable to view the carbon-based ink of these papyri, even when they could
      penetrate the different layers of their spiral structure. Here for the first
      time, we show that X-ray phase-contrast tomography can reveal various letters
      hidden inside the precious papyri without unrolling them. This attempt opens up
      new opportunities to read many Herculaneum papyri, which are still rolled up,
      thus enhancing our knowledge of ancient Greek literature and philosophy. 

PMID- 25603113
TI  - Topographic diversity of the respiratory tract mycobiome and alteration in HIV
      and lung disease.
AB  - RATIONALE: Microbiome studies typically focus on bacteria, but fungal species are
      common in many body sites and can have profound effects on the host. Wide gaps
      exist in the understanding of the fungal microbiome (mycobiome) and its
      relationship to lung disease. OBJECTIVES: To characterize the mycobiome at
      different respiratory tract levels in persons with and without HIV infection and
      in HIV-infected individuals with chronic obstructive pulmonary disease (COPD).
      METHODS: Oral washes (OW), induced sputa (IS), and bronchoalveolar lavages (BAL)
      were collected from 56 participants. We performed 18S and internal transcribed
      spacer sequencing and used the neutral model to identify fungal species that are
      likely residents of the lung. We used ubiquity-ubiquity plots, random forest,
      logistic regression, and metastats to compare fungal communities by HIV status
      and presence of COPD. MEASUREMENTS AND MAIN RESULTS: Mycobiomes of OW, IS, and
      BAL shared common organisms, but each also had distinct members. Candida was
      dominant in OW and IS, but BAL had 39 fungal species that were disproportionately
      more abundant than in the OW. Fungal communities in BAL differed significantly by
      HIV status and by COPD, with Pneumocystis jirovecii significantly overrepresented
      in both groups. Other fungal species were also identified as differing in HIV and
      COPD. CONCLUSIONS: This study systematically examined the respiratory tract
      mycobiome in a relatively large group. By identifying Pneumocystis and other
      fungal species as overrepresented in the lung in HIV and in COPD, it is the first
      to determine alterations in fungal communities associated with lung dysfunction
      and/or HIV, highlighting the clinical relevance of these findings. Clinical trial
      registered with www.clinicaltrials.gov (NCT00870857).

PMID- 25603116
TI  - Preparation, characterization, and preliminary antibrowning evaluations of
      norartocarpetin microemulsions.
AB  - Norartocarpetin is a flavone widely distributed in Moraceae plants with strong
      tyrosinase inhibitory activity. However, its poor solubility in aqueous systems
      and in food grade solvents (oils) limits its extensive applications. The aim of
      this study was to improve the solubility of norartocarpetin by developing an oil
      in-water (o/w) microemulsion with food grade components. A microemulsion was
      developed and characterized, and its chemical and physical stabilities were also
      evaluated within 8 weeks. Using the construction of pseudoternary phase diagrams,
      the optimized formulation of 2% w/w of ethyl oleate, 12% w/w of Tween 80, 6% w/w
      of polyethylene glycol 400, and 80% w/w of water was obtained, with a maximum
      solubility of norartocarpetin up to 1.73 +/- 0.21 mg/mL, at least a 1000-fold
      increase in solubility. The microemulsion base and norartocarpetin-loaded
      microemulsion were demonstrated to be stable after accelerated and long-term
      conditions (8 weeks). The norartocarpetin microemulsion still showed strong
      tyrosinase inhibitory activity and antibrowning effect on fresh-cut apple slices.
      These combined results indicated that norartocarpetin microemulsion may be
      suitable as an antibrowning agent for fresh-cut fruits.

PMID- 25603115
TI  - Births: final data for 2013.
AB  - OBJECTIVES: This report presents 2013 data on U.S. births according to a wide
      variety of characteristics. Data are presented for maternal age, live-birth
      order, race and Hispanic origin, marital status, attendant at birth, method of
      delivery, period of gestation, birthweight, and plurality. Birth and fertility
      rates are presented by age, live-birth order, race and Hispanic origin, and
      marital status. Selected data by mother's state of residence and birth rates by
      age and race of father also are shown. Trends in fertility patterns and maternal
      and infant characteristics are described and interpreted. METHODS: Descriptive
      tabulations of data reported on the birth certificates of the 3.93 million U.S.
      births that occurred in 2013 are presented. RESULTS: A total of 3,932,181 births
      were registered in the United States in 2013, down less than 1% from 2012. The
      general fertility rate declined to 62.5 per 1,000 women aged 15-44. The teen
      birth rate fell 10%, to 26.5 per 1,000 women aged 15-19. Birth rates declined for
      women in their 20s and increased for most age groups of women aged 30 and over.
      The total fertility rate (estimated number of births over a woman's lifetime)
      declined 1% to 1,857.5 per 1,000 women. Measures of unmarried childbearing were
      down in 2013 from 2012. The cesarean delivery rate declined to 32.7%. The preterm
      birth rate declined for the seventh straight year to 11.39%, but the low
      birthweight rate was essentially unchanged at 8.02%. The twin birth rate rose 2%
      to 33.7 per 1,000 births; the triplet and higher-order multiple birth rate
      dropped 4% to 119.5 per 100,000 total births.

PMID- 25603117
TI  - Formation mechanisms of GaN nanowires grown by selective area growth homoepitaxy.
AB  - This work provides experimental evidence and theoretical explanations regarding
      the formation mechanisms of GaN nanowires grown by selective area growth on GaN
      on-sapphire templates. The first growth stage, driven by selective area growth
      kinetics, consists of initial nucleation (along the nanohole inner periphery),
      coalescence onset and full coalescence, producing a single nanocrystal within
      each nanohole. In the second growth stage, driven by free-surface-energy
      minimization, the formed nanocrystal undergoes morphological evolution,
      exhibiting initial cylindrical-like shape, intermediate dodecagonal shape and a
      final, thermodynamically stable hexagonal shape. From this point on, the nanowire
      vertical growth proceeds while keeping the stable hexagonal form. 

PMID- 25603118
TI  - Identity elements for the aminoacylation of metazoan mitochondrial tRNA(Arg) have
      been widely conserved throughout evolution and ensure the fidelity of the AGR
      codon reassignment.
AB  - Eumetazoan mitochondrial tRNAs possess structures (identity elements) that
      require the specific recognition by their cognate nuclear-encoded aminoacyl-tRNA
      synthetases. The AGA (arginine) codon of the standard genetic code has been
      reassigned to serine/glycine/termination in eumetazoan organelles and is
      translated in some organisms by a mitochondrially encoded tRNA(Ser)UCU. One
      mechanism to prevent mistranslation of the AGA codon as arginine would require a
      set of tRNA identity elements distinct from those possessed by the cytoplasmic
      tRNAArg in which the major identity elements permit the arginylation of all 5
      encoded isoacceptors. We have performed comparative in vitro aminoacylation using
      an insect mitochondrial arginyl-tRNA synthetase and tRNAArgUCG structural
      variants. The established identity elements are sufficient to maintain the
      fidelity of tRNASerUCU reassignment. tRNAs having a UCU anticodon cannot be
      arginylated but can be converted to arginine acceptance by identity element
      transplantation. We have examined the evolutionary distribution and functionality
      of these tRNA elements within metazoan taxa. We conclude that the identity
      elements that have evolved for the recognition of mitochondrial tRNAArgUCG by the
      nuclear encoded mitochondrial arginyl-tRNA synthetases of eumetazoans have been
      extensively, but not universally conserved, throughout this clade. They ensure
      that the AGR codon reassignment in eumetazoan mitochondria is not compromised by
      misaminoacylation. In contrast, in other metazoans, such as Porifera, whose
      mitochondrial translation is dictated by the universal genetic code, recognition
      of the 2 encoded tRNAArgUCG/UCU isoacceptors is achieved through structural
      features that resemble those employed by the yeast cytoplasmic system. 

PMID- 25603119
TI  - Impaired tropomyosin-troponin interactions reduce activation of the actin thin
      filament.
AB  - Tropomyosin and troponin are bound to the actin filament to control the
      contraction of striated muscle in the Ca-dependent manner. The interactions
      between both regulatory proteins important for the regulation process are not
      fully understood. To gain more insight into the mechanisms of the thin filament
      regulation by skeletal alpha-tropomyosin and troponin, we analyzed effects of
      seven myopathy-related substitutions: Leu99Met, Ala155Thr, Arg167Gly, Arg167Cys,
      Arg167His, Lys168Glu, and Arg244Gly. All substitutions reduced Ca-dependent
      activation of the actomyosin ATPase. The effects of mutations in Arg167 and
      Lys168 were the most severe. The amino acid substitutions did not significantly
      affect troponin binding to the whole filament, but reduced 1.2-2.8 fold the
      affinity of troponin to tropomyosin alone. The excimer fluorescence of N-(1
      pyrene)iodoacetamide, a probe attached to the central Cys190, demonstrated that
      substitutions located near the troponin core domain-binding region strongly
      affected conformational changes accompanying the tropomyosin-troponin
      interactions. The thermal stability of all tropomyosin mutants was lower than the
      stability of the wild type tropomyosin, with TM reduced by 5.3-8.5 degrees C.
      Together the analyses demonstrated that the myopathy-causing mutations affected
      tropomyosin structure and led to changes in interactions between tropomyosin and
      troponin, which impaired the transition of the thin filament from the inactive
      off to the active on state. 

PMID- 25603120
TI  - The information value of non-genetic inheritance in plants and animals.
AB  - Parents influence the development of their offspring in many ways beyond the
      transmission of DNA. This includes transfer of epigenetic states, nutrients,
      antibodies and hormones, and behavioural interactions after birth. While the
      evolutionary consequences of such non-genetic inheritance are increasingly well
      understood, less is known about how inheritance mechanisms evolve. Here, we
      present a simple but versatile model to explore the adaptive evolution of non
      genetic inheritance. Our model is based on a switch mechanism that produces
      alternative phenotypes in response to different inputs, including genes and non
      genetic factors transmitted from parents and the environment experienced during
      development. This framework shows how genetic and non-genetic inheritance
      mechanisms and environmental conditions can act as cues by carrying correlational
      information about future selective conditions. Differential use of these cues is
      manifested as different degrees of genetic, parental or environmental morph
      determination. We use this framework to evaluate the conditions favouring non
      genetic inheritance, as opposed to genetic determination of phenotype or within
      generation plasticity, by applying it to two putative examples of adaptive non
      genetic inheritance: maternal effects on seed germination in plants and
      transgenerational phase shift in desert locusts. Our simulation models show how
      the adaptive value of non-genetic inheritance depends on its mechanism, the pace
      of environmental change, and life history characteristics. 

PMID- 25603121
TI  - Resuscitation algorithms-linear or circular?

PMID- 25603122
TI  - A series of novel terpyridine-skeleton molecule derivants inhibit tumor growth
      and metastasis by targeting topoisomerases.
AB  - A series of novel terpyridine-skeleton molecules containing conformational
      rigidity, 14 containing benzo[4,5]furo[3,2-b]pyridine core and 15 comprising
      chromeno[4,3-b]pyridine core, were synthesized, and their biological activities
      were evaluated. 3-(4-Phenylbenzo[4,5]furo[3,2-b]pyridin-2-yl)phenol (8) was
      determined to be a nonintercalative topo I and II dual catalytic inhibitor and 3
      (4-phenylchromeno[4,3-b]pyridine-2-yl)phenol (22) was determined to be a
      nonintercalative topo IIalpha specific catalytic inhibitor by various assays.
      These two catalytic inhibitors induced apoptosis in addition to G1 arrest in T47D
      human breast cancer cells with much less DNA toxicity than etoposide. Compounds 8
      and 22 significantly inhibited tumor growth in HCT15 subcutaneously implanted
      xenografted mice. The modification of compounds 8 and 22 with the introduction of
      a methoxy instead of a hydroxy group enhanced endogenous topo inhibitory
      activity, metabolic stability in diverse types of liver microsomes and improved
      pharmacokinetic parameters in rat plasma such as augmentation of bioavailability
      (41.3% and 33.2% for 2-(3-methoxyphenyl)-4-phenylbenzofuro[3,2-b]pyridine (8-M)
      and 3-(4-phenylchromeno[4,3-b]pyridine-2-yl)methoxybenzene (22-M), respectively).

PMID- 25603123
TI  - Intra-arterial DynaCT angiography: an alternative tool to assess the patency of
      intracranial stent lumen.
AB  - OBJECTIVE: The aim of this retrospective study was to assess the clinical utility
      of intra-arterial DynaCT angiographic imaging for the evaluation of intracranial
      stent patency. METHODS: Between July 2011 and May 2014, 35 patients with
      symptomatic intracranial atherosclerotic stenosis (ICAS) were treated with
      percutaneous transluminal angioplasty and stents. All were evaluated with intra
      arterial DynaCT angiographic imaging during the operations and follow-up. All
      images were further processed with three different kernels (sharp, normal, or
      smooth). RESULTS: Thirty-six stents were implanted into the parent arteries.
      DynaCT provided "good" quality images (median score of 2 or 3 on a 5-point scale)
      with minimal artifact interference as rated by observers blind to treatment
      history and other imaging results. The median subjective visibility score was
      highest (3) using the sharp kernel. CONCLUSIONS: DynaCT with sharp kernel image
      processing achieved good visualization of luminal patency following intracranial
      stents.

PMID- 25603124
TI  - Autonomic predominant multiple system atrophy in the context of Parkinsonian and
      cerebellar variants.
AB  - OBJECTIVES: Autonomic dysfunction is often a late feature of multiple system
      atrophy (MSA). Based on early features, MSAp (Parkinsonian) and MSAc (cerebellar)
      variants are known. We studied the severity of autonomic dysfunction at first
      examination in MSA patient that may have relevance in its early diagnosis.
      METHODS: Clinical (including autonomic), radiological and lab features of 53 MSA
      patients were analyzed in the context of MSAp (16 patients) and MSAc (37
      patients). RESULTS: Most frequent autonomic symptoms were erectile dysfunction in
      30 out of 38 males (78.9%), bladder symptoms in 35 (66%), followed by
      blackouts/fainting attacks in 33 (62.3%). Autonomic abnormalities were detected
      in hand grip test (86.8%), deep breathing test (79.2%), cold pressor test
      (71.7%), Valsalva maneuver (75.5%), heart rate variability at 30:15 beats after
      standing (50.9%) and systolic BP on standing (41.5%). Six (16.2%) MSAp and 1
      (6.3%) MSAc patients continued to have autonomic symptoms for several months
      (38.7+/-26.11, median 36 months) before the appearance of cerebellar (1 patient)
      or Parkinsonian (6 patients) features. CONCLUSION: Autonomic dysfunction may be
      the only presenting feature in some patients with MSA. Routine autonomic testing
      may help in the early diagnosis of MSA in patients presenting with Parkinsonian
      or cerebellar features.

PMID- 25603125
TI  - Functional and sensory evaluation of patients with idiopathic trigeminal
      neuralgia: comparison with controls.
AB  - BACKGROUND: Idiopathic trigeminal neuralgia (ITN) can be associated with
      orofacial and sensory comorbidities. OBJECTIVE: To evaluate the masticatory
      functional and sensory characteristics of patients with ITN compared with
      controls. METHODS: We enrolled 119 patients and 30 healthy controls. They were
      evaluated with a systematic protocol: clinical orofacial evaluation
      questionnaire; a systematic approach of the mandibular function and the
      investigation of musculoskeletal comorbidities by the research diagnostic
      criteria for temporomandibular disorders (RDC/TMD) and the Helkimo indexes; and
      quantitative sensory testing (corneal reflex and gustative, olfactory, thermal,
      mechanical and pain thresholds). RESULTS: The study group had more loss of
      vertical dimension than the controls (p=0.011) and restriction of the maximum
      mouth opening (p=0.024); they had more pain on mandibular movements (p=0.001),
      limitation of mandibular function (p<0.001), masticatory discomfort (p<0.001) and
      myofascial pain (p=0.001). Occlusion Helkimo index was lower in controls than
      patients. The study group had high tactile (p=0.025), warm (p=0.020) and cold
      (p=0.003) thresholds. CONCLUSION: ITN may cause severe mandibular limitations
      that can be associated with the pain episodes and with sensory abnormalities.
      These findings indicate the affection of small and large nerve fibers and support
      the neuropathic nature of ITN. Sensory alterations can be part of the natural
      history of ITN and can be associated with the previous treatments including
      medication. They cause a high impact in quality of life.

PMID- 25603126
TI  - Altered spontaneous brain activity in patients with hemifacial spasm: a resting
      state functional MRI study.
AB  - Resting-state functional magnetic resonance imaging (fMRI) has been used to
      detect the alterations of spontaneous neuronal activity in various neurological
      and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous
      system disorder. We used resting-state fMRI with regional homogeneity (ReHo)
      analysis to investigate changes in spontaneous brain activity of patients with
      HFS and to determine the relationship of these functional changes with clinical
      features. Thirty patients with HFS and 33 age-, sex-, and education-matched
      healthy controls were included in this study. Compared with controls, HFS
      patients had significantly decreased ReHo values in left middle frontal gyrus
      (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior
      temporal gyrus (STG) and right precuneus; and increased ReHo values in left
      precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right
      cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive
      correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo
      value in MFG was inversely related with spasm severity in HFS group (r = -0.398,
      p = 0.028). This study reveals that HFS is associated with abnormal spontaneous
      brain activity in brain regions most involved in motor control and blinking
      movement. The disturbances of spontaneous brain activity reflected by ReHo
      measurements may provide insights into the neurological pathophysiology of HFS. 

PMID- 25603127
TI  - Determination of Dietary Status as a Risk Factor of Cardiovascular Heart Disease
      in Turkish Elderly People.
AB  - This study was performed to determine the status of diet as a risk factor of
      cardiovascular heart disease in a group of Turkish elderly people. We performed a
      cross-sectional study using the data of voluntary participants aged between 65-74
      years old. Participants completed 3-day diet records. Of participants, 64.1% of
      the men and 62.2% of the women reported their daily dietary fat intake as being >
      30% of total energy (p > .05). More than 20% of these elderly respondents' daily
      intakes of vitamin E, vitamin B6, vitamin B12, and folate were found to be under
      the recommended values. As a result, the total fat intake of these elderly people
      was found to be high; while their intake of fiber and vitamin B6, vitamin B12
      were found to be low, compared to American Heart Association recommendations. In
      conclusion, it is recommended that developing sufficient and balanced diets may
      decrease cardiovascular risk factors. 

PMID- 25603128
TI  - The Qiagen Investigator(r) Quantiplex HYres as an alternative kit for DNA
      quantification.
AB  - The Investigator(r) Quantiplex HYres kit was evaluated as a potential replacement
      for dual DNA quantification of casework samples. This kit was determined to be
      highly sensitive with a limit of quantification and limit of detection of
      0.0049ng/MUL and 0.0003ng/MUL, respectively, for both human and male DNA, using
      full or half reaction volumes. It was also accurate in assessing the amount of
      male DNA present in 96 mock and actual casework male:female mixtures (various
      ratios) processed in this exercise. The close correlation between the male/human
      DNA ratios expressed in percentages derived from the Investigator(r) Quantiplex
      HYres quantification results and the male DNA proportion calculated in mixed
      AmpFlSTR(r) Profiler(r) Plus or AmpFlSTR(r) Identifiler(r) Plus profiles, using
      the Amelogenin Y peak and STR loci, allowed guidelines to be developed to
      facilitate decisions regarding when to submit samples to Y-STR rather than
      autosomal STR profiling. The internal control (IC) target was shown to be more
      sensitive to inhibitors compared to the human and male DNA targets included in
      the Investigator(r) Quantiplex HYres kit serving as a good quality assessor of
      DNA extracts. The new kit met our criteria of enhanced sensitivity, accuracy,
      consistency, reliability and robustness for casework DNA quantification.

PMID- 25603129
TI  - Molecular structure and pronounced conformational flexibility of doxorubicin in
      free and conjugated state within a drug-peptide compound.
AB  - The search for targeted drug delivery systems requires the design of drug-carrier
      complexes, which could both reach the malignant cells and preserve the
      therapeutic substance activity. A promising strategy aimed at enhancing the
      uptake and reducing the systemic toxicity is to bind covalently the drug to a
      cell-penetrating peptide. To understand the structure-activity relationship in
      such preparations, the chemotherapeutic drug doxorubicin was investigated by
      unrestrained molecular dynamics simulations, supported by NMR, which yielded its
      molecular geometry in aqueous environment. Furthermore, the structure and
      dynamics of a conjugate of the drug with a cell-penetrating peptide was obtained
      from molecular dynamics simulations in aqueous solution. The geometries of the
      unbound compounds were characterized at different temperatures, as well as the
      extent to which they change after covalent binding and whether/how they influence
      each other in the drug-peptide conjugate. The main structural fragments that
      affect the conformational ensemble of every molecule were found. The results show
      that the transitions between different substructures of the three compounds
      require a modest amount of energy. At increased temperature, either more
      conformations become populated as a result of the thermal fluctuations or the
      relative shares of the various conformers equalize at the nanosecond scale. These
      frequent structural interconversions suggest expressed conformational freedom of
      the molecules. Conjugation into the drug-peptide compound partially immobilizes
      the molecules of the parent compounds. Nevertheless, flexibility still exists, as
      well as an effective intra- and intermolecular hydrogen bonding that stabilizes
      the structures. We observe compact packing of the drug within the peptide that is
      also based on stacking interactions. All this outlines the drug-peptide conjugate
      as a prospective building block of a more complex drug-carrier system. 

PMID- 25603130
TI  - Psychophysiological responses to unpredictable threat: effects of cue and
      temporal unpredictability.
AB  - Although threat unpredictability plays an important role in determining emotional
      responses, little is known about what elements of unpredictability are
      responsible for these results. The current study examined the single and combined
      effects of two elements of unpredictable threat: (a) uncertainty about the timing
      of an aversive event (temporal unpredictability), and (b) uncertainty about
      whether an aversive event will occur at all (cue unpredictability). Seventy-two
      healthy young adult participants were randomly assigned to receive either
      temporally predictable or unpredictable shocks at varying levels of cue
      unpredictability. Dependent variables included skin conductance responses (SCRs)
      and eyeblink startle reflex. Combined cue and temporal unpredictability elicited
      weaker SCRs than either element of unpredictability alone, indicating that high
      unpredictability may induce anxiety-like physiological inhibition. Combined cue
      and temporal unpredictability and combined cue and temporal predictability
      produced the largest startle. Findings provide evidence that both cue and
      temporal unpredictability should be included in human models of anxiety.

PMID- 25603131
TI  - Quality of social experience explains the relation between extraversion and
      positive affect.
AB  - The personality trait extraversion is associated with higher positive affect, and
      individuals who behave in an extraverted way experience increased positive
      affect. Across 2 studies, we examine whether the positive affectivity of
      extraverts can be explained in terms of qualitative aspects of social experience
      resulting from extraverted (i.e., bold, assertive) behavior. In our first study
      (N = 225, 58% female), we found that social well-being, a broad measure of
      quality of social life (Keyes, 1998) was a significant mediator of the relation
      between trait extraversion and trait positive affect. This effect was specific to
      1 aspect of social well-being-social contribution, one's sense of making an
      impact on one's social world. In our second study (N = 81, 75% female), we found
      that a momentary assessment of social well-being mediated the effect of
      experimentally manipulated extraverted behavior (in the context of 2 brief
      discussion tasks) on state positive affect. Furthermore, perceived contribution
      to the discussion tasks accounted for up to 70% of the effect of enacted
      extraversion on positive affect. This is the first identified mediator of the
      effect of enacted extraversion on positive affect. Implications and suggestions
      for extensions of this research are discussed.

PMID- 25603132
TI  - Attentional and emotional prioritization of the sounds occurring outside the
      visual field.
AB  - The ability to detect and localize sounds in an environment is critical for
      survival. Localizing sound sources is a computational challenge for the human
      brain because the auditory cortex seems to lack a topographical space
      representation. However, attention and task demands can modulate localization
      performance. Here, we investigated whether the localization performance for
      sounds occurring directly in front of or behind people could be modulated by
      emotional salience and sound-source location. We measured auditory-induced
      emotion by ecological sounds occurring in the frontal or rear perceptual fields,
      and employed a speeded localization task. The results showed that both
      localization speed and accuracy were higher, and that stronger negative emotions
      were induced when sound sources were behind the participants. Our results provide
      clear behavioral evidence that auditory attention can be influenced by sound
      source location. Importantly, we also show that the effect of spatial location on
      attention is mediated by emotion, which is in line with the argument that
      emotional information is prioritized in processing. Auditory system functions as
      an alarm system and is in charge of detecting possible salient events, and
      alarming for an attention shift. Further, spatial processing in the auditory
      dorsal pathway has a function of guiding the visual system to a particular
      location of interest. Thus, an auditory bias toward the space outside the visual
      field can be useful, so that visual attention could be quickly shifted in case of
      emotionally significant information.

PMID- 25603133
TI  - Positive affect and markers of inflammation: discrete positive emotions predict
      lower levels of inflammatory cytokines.
AB  - Negative emotions are reliably associated with poorer health (e.g., Kiecolt
      Glaser, McGuire, Robles, & Glaser, 2002), but only recently has research begun to
      acknowledge the important role of positive emotions for our physical health
      (Fredrickson, 2003). We examine the link between dispositional positive affect
      and one potential biological pathway between positive emotions and health
      proinflammatory cytokines, specifically levels of interleukin-6 (IL-6). We
      hypothesized that greater trait positive affect would be associated with lower
      levels of IL-6 in a healthy sample. We found support for this hypothesis across
      two studies. We also explored the relationship between discrete positive emotions
      and IL-6 levels, finding that awe, measured in two different ways, was the
      strongest predictor of lower levels of proinflammatory cytokines. These effects
      held when controlling for relevant personality and health variables. This work
      suggests a potential biological pathway between positive emotions and health
      through proinflammatory cytokines.

PMID- 25603136
TI  - Self-affirmation breaks the link between the behavioral inhibition system and the
      threat-potentiated startle response.
AB  - Reflecting on core personal values is a common means of self-affirmation that can
      change how a person responds to threatening events. Specifically, self
      affirmation has been found to reduce psychological defenses against self-esteem
      threats. The current research examined the effects of self-affirmation on more
      basic reflexive mechanisms of motivation and emotion. The startle-eyeblink
      response is a defensive reflex that can be elicited by loud bursts of noise and
      is potentiated in the presence of threatening stimuli. Individual differences in
      anxiety-related traits, including behavioral inhibition-system (BIS) sensitivity,
      predict the magnitude of threat-potentiated startle responses, such that higher
      BIS sensitivity corresponds with more intense responses to threatening stimuli.
      The current experiment (N = 100) tested the hypothesis that affirming a core
      personal value breaks the link between BIS sensitivity and threat responsiveness.
      We measured individual differences in BIS, manipulated the opportunity for self
      affirmation, and assessed eyeblink responses to startle probes during negative,
      neutral, and positive emotional picture viewing. In the no-affirmation condition,
      BIS sensitivity predicted the magnitude of startle-eyeblink responses during
      negative pictures, consistent with previous research. In the self-affirmation
      condition, the relationship between BIS sensitivity and threat-potentiated
      startle responding was eliminated. This finding suggests that self-affirmation's
      effects extend beyond self-esteem defenses to influence basic defensive reflexes
      in threat-prone individuals. (PsycINFO Database Record 

PMID- 25603134
TI  - Valuing happiness is associated with bipolar disorder.
AB  - Although people who experience happiness tend to have better psychological
      health, people who value happiness to an extreme tend to have worse psychological
      health, including more depression. We propose that the extreme valuing of
      happiness may be a general risk factor for mood disturbances, both depressive and
      manic. To test this hypothesis, we examined the relationship between the extreme
      valuing of happiness and risk for, diagnosis of, and illness course for bipolar
      disorder (BD). Supporting our hypothesis, the extreme valuing of happiness was
      associated with a measure of increased risk for developing BD (Studies 1 and 2),
      increased likelihood of past diagnosis of BD (Studies 2 and 3), and worse
      prospective illness course in BD (Study 3), even when controlling for current
      mood symptoms (Studies 1-3). These findings indicate that the extreme valuing of
      happiness is associated with and even predicts BD. Taken together with previous
      evidence, these findings suggest that the extreme valuing of happiness is a
      general risk factor for mood disturbances. More broadly, what emotions people
      strive to feel may play a critical role in psychological health.

PMID- 25603135
TI  - Why do fearful facial expressions elicit behavioral approach? Evidence from a
      combined approach-avoidance implicit association test.
AB  - Despite communicating a "negative" emotion, fearful facial expressions
      predominantly elicit behavioral approach from perceivers. It has been
      hypothesized that this seemingly paradoxical effect may occur due to fearful
      expressions' resemblance to vulnerable, infantile faces. However, this hypothesis
      has not yet been tested. We used a combined approach-avoidance/implicit
      association test (IAT) to test this hypothesis. Participants completed an
      approach-avoidance lever task during which they responded to fearful and angry
      facial expressions as well as neutral infant and adult faces presented in an IAT
      format. Results demonstrated an implicit association between fearful facial
      expressions and infant faces and showed that both fearful expressions and infant
      faces primarily elicit behavioral approach. The dominance of approach responses
      to both fearful expressions and infant faces decreased as a function of
      psychopathic personality traits. Results suggest that the prosocial responses to
      fearful expressions observed in most individuals may stem from their associations
      with infantile faces. (PsycINFO Database Record 

PMID- 25603137
TI  - Lean on me: susceptibility to partner affect attenuates psychological distress
      over a 12-month period.
AB  - Symptoms of psychological distress are associated with the experience of
      heightened negative affect, and the inability to successfully regulate one's
      emotions. Romantic partners can, however, influence and regulate each other's
      emotional experiences, especially during times of distress. Using daily diary
      measures taken 4 times per day over a 10-day period, we examined whether
      susceptibility to partner affect was associated with levels and trajectories of
      psychological distress over 12 months. Results from both partners of 103
      committed relationships (206 individuals) found that men and women showed
      decreased levels of distress over the year when they were more susceptible to
      their partner's positive affect, but the degree of susceptibility varied with
      respect to negative affect. Examining susceptibility to partner affect may be a
      valuable complementary approach to studying relational contributions to the
      social regulation of emotions, especially in understanding the progression of
      psychological distress.

PMID- 25603138
TI  - Experimental study of hemodynamics in the Circle of Willis.
AB  - BACKGROUND: The Circle of Willis (CoW) is an important collateral pathway of the
      cerebral blood flow. An experimental study of the cerebral blood flow (CBF)
      distribution in different anatomical variations may help to a better
      understanding of the collateral mechanism of the CoW. METHODS: An in-vitro test
      rig was developed to simulate the physiological cerebral blood flow in the CoW.
      Ten anatomical variations were considered in this study, include a set of
      different degrees of stenosis in L-ICA and L-ICA occlusion coexist with common
      anatomical variations. Volume flow rates of efferent arteries and pressure
      signals at the end of communicating arteries of each case were recorded.
      Physiological pressure waveforms were applied as inlet boundary condition.
      RESULTS: In the development of L-ICA stenosis, the total CBF decreases with the
      increase of stenosis degree. The blood supply of ipsilateral middle cerebral
      artery (MCA) was affected most by the stenosis of L-ICA. Anterior communicating
      artery (ACoA) and ipsilateral posterior communicating artery (PCoA) function as
      important collateral pathways of cerebral collateral circulation when unilateral
      stenosis occurred. The blood supply of anterior cerebral circulation was
      compensated by the posterior cerebral circulation through ipsilateral PCoA when L
      ICA stenosis degree is greater than 40% and the affected side was compensated
      immediately by the unaffected side through ACoA. Blood flow of the anterior
      circulation and the total CBF reached the minimum among all cases studied when L
      ICA occlusion coexist with the absence of PCoA. CONCLUSION: The results
      demonstrated the flow distribution patterns of the CoW under anatomical
      variations and clarified the collateral mechanism of the CoW. The flow ACoA is
      the most sensitive indexes to the morphology change of ipsilateral ICA. The
      relative independence of the circulation in anterior and posterior sections of
      the CoW is not broken and the function of ipsilateral PCoA is not activated until
      a severe stenosis of unilateral ICA occurs. PCoA is the most important collateral
      pathway of the collateral circulation and the missing of PCoA has the highest
      risk of stroke when the ipsilateral ICA has severe stenosis. These findings may
      provide the basis for future therapeutic and diagnosis applications.

PMID- 25603140
TI  - Role of seaweed laminaran from Saccharina longicruris on matrix deposition during
      dermal tissue-engineered production.
AB  - Our laboratory has developed a technique to reconstruct in vitro tissue from
      human cells using the self-assembly tissue-engineering method, which utilizes the
      ability of fibroblasts to deposit the matrix they secrete. The time necessary for
      tissue construction, several weeks, is a drawback for many clinical uses. We
      hypothesized that the addition of laminaran can increase the deposition of
      matrix, speeding up the production of the tissue. Laminaran was isolated from the
      brown seaweed Saccharina longicruris harvested in Canada and its structure was
      evaluated. Laminaran is a small molecular weight polysaccharide composed of
      linear glucose chains. Monolayer-cultured human skin fibroblasts were cultured in
      the presence of laminaran with ascorbate for 7 or 35 days to produce a dermis.
      Treatment did not induce any variation in the growth rate or alpha smooth muscle
      actin content but it did increase the deposition of collagen I in a dose
      dependent manner. After 35 days, the reconstructed dermal thickness was increased
      when laminaran was added, and collagen I deposition and MMP activity were also
      significantly increased. Thus, laminaran can be used to increase the rate of
      production of reconstructed self-assembled dermis and can also potentially be
      used in cosmetic or therapeutic creams to stimulate matrix production. 

PMID- 25603139
TI  - Asp residues of betaDELSEED-motif are required for peptide binding in the
      Escherichia coli ATP synthase.
AB  - This study demonstrates the requirement of Asp-380 and Asp-386 in the betaDELSEED
      motif of Escherichia coli ATP synthase for peptide binding and inhibition. We
      studied the inhibition profiles of wild-type and mutant E. coli ATP synthase in
      presence of c-terminal amide bound melittin and melittin related peptide.
      Melittin and melittin related peptide inhibited wild-type ATPase almost
      completely while only partial inhibition was observed in single mutations with
      replacement of Asp to Ala, Gln, or Arg. Additionally, very little or no
      inhibition occurred among double mutants betaD380A/betaD386A,
      betaD380Q/betaD386Q, or betaD380R/betaD386R signifying that removal of one Asp
      residue allows limited peptide binding. Partial or substantial loss of oxidative
      phosphorylation among double mutants demonstrates the functional requirement of
      betaD380 and betaD386 Asp residues. Moreover, abrogation of wild-type E. coli
      cell growth and normal growth of mutant cells in presence of peptides provides
      strong evidence for the requirement of betaDELSEED-motif Asp residues for peptide
      binding. It is concluded that while presence of one Asp residue may allow partial
      peptide binding, both Asp residues, betaD380 and betaD386, are essential for
      proper peptide binding and inhibition of ATP synthase. 

PMID- 25603141
TI  - An enhanced protein-protein interaction based on enzymatic complex through
      replacement of the recognition site.
AB  - Clostridium cellulovorans, produce multi-enzymatic complexes known as
      cellulosomes, which assemble via the interaction of a dockerin module in the
      cellulosomal subunit with one of the several cohesin modules in the scaffolding
      protein, to degrade the plant cell wall polymer. An enhanced cohesin-dockerin
      interaction was demonstrated by modified certain cellulosomal enzymes with
      altered amino acid residues at the crucial binding site, 11th and 12th positions
      in dockerin module. In fluorescence intensity analyses using the cellulosome
      based biomarker system, the modified cellulosomal enzymes (EngE SL to AI and EngH
      SM to AI) showed an increased intensity (1.4- to 2.2-fold) compared with the wild
      type proteins. Conversely, modified ExgS (AI to SM) exhibited a reduced intensity
      (0.6- to 0.7-fold) compared with the wild type. In enzyme-linked and competitive
      enzyme-linked interaction assays, the some modified protein (EngE SL to AI and
      EngH SM to AI) showed their increased binding affinity toward the cohesins (Coh2
      and Coh9). Surface plasmon resonance analysis quantitatively demonstrated the
      binding affinity of these two modified proteins toward cohesins showed similar or
      higher affinity comparing with its with wild type proteins. These results suggest
      the replacement of amino acid residues in the certain recognition site
      significantly affects the binding affinity of the cohesin-dockerin interaction. 

PMID- 25603142
TI  - Structural characterization of lignin: a potential source of antioxidants
      guaiacol and 4-vinylguaiacol.
AB  - The structure of lignin obtained from the ozone and soaking aqueous ammonia
      pretreatment of wheat straw has been characterized utilizing chemical analytical
      methods in order to reveal its antioxidant characteristics, including attenuated
      total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), pyrolysis
      gas chromatography/mass spectrometry (Py-GC/MS), pyrolysis/tetramethylammonium
      hydroxide-gas chromatography/mass spectrometry (Py/TMAH-GC/MS), gel permeation
      chromatography (GPC), ultra violet-visible spectroscopy (UV-vis), and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) antioxidant evaluation assay. The results
      demonstrated that the isolated lignin is a rho-hydroxyphenyl- guaiacyl-syringyl
      (H-G-S) lignin, with S/G ratio of 0.35 and significant amounts of phenol 2
      methoxy (guaiacol) and phenol 2-methoxy-4-vinyl (4-vinylguaiacol). The Py-GC/MS
      and Py/TMAH-GC/MS pyrograms indicated that the major units in this lignin are
      derived from hydroxycinnamic acids. The GPC results revealed the molecular weight
      of the lignin was considerably low and also the FTIR analysis showed that the
      lignin possessed hydroxyl and methoxy functional groups; the factors led to the
      extracted lignin having a comparable antioxidant activity to that of currently
      used commercial antioxidants. The UV-vis and DPPH antioxidant assay results
      suggested a percentage of inhibition of the DPPH radicals in the following order:
      guaiacol (103.6 +/- 1.36)>butylated hydroxytoluene (103.3 +/- 1)>ferulic acid
      (102.6 +/- 0.79)>pretreated lignin (86.9 +/- 0.34).

PMID- 25603143
TI  - Agar-agar entrapment increases the stability of endo-beta-1,4-xylanase for
      repeated biodegradation of xylan.
AB  - Microbial xylanases, specially endo-beta-1,4-xylanase catalyzes the hydrolysis of
      xylan, is considered one of the most significant hydrolases. It has numerous
      applications but most extensively is utilized in paper and pulp industry as a bio
      bleaching agent. Immobilization technique is comprehensively studied with the
      expectation of modifying and improving enzyme stability and characteristics for
      commercial purposes. Currently, matrix entrapment technique is applied to
      immobilize endo-beta-1,4-xylanase within agar-agar gel beads produced by
      Geobacillus stearothermophilus KIBGE-IB29. Maximal enzyme immobilization yield
      was achieved at 2.5% of agar-agar concentration. Optimized conditions
      demonstrated an increase in the optimal reaction time from 05 min to 30 min and
      incubation temperature from 50  degrees C to 60  degrees C with reference to free
      enzyme whereas; no effect was observed for optimum pH. Entrapment technique
      uniquely changed the kinetic parameters of immobilized endo-beta-1,4-xylanase
      (Km: 0.5074 mg min(-1) to 0.5230 mg min(-1) and Vmax: 4773 U min(-1) to 968 U
      min(-1)) as compared to free enzyme. However, immobilized enzyme displayed broad
      thermal stability and retained 79.0% of its initial activity at 80  degrees C up
      to 30 min whereas; free enzyme completely lost its activity at this temperature.
      With respect to economic feasibility, the immobilized enzyme showed impressive
      recycling efficiency up to six reaction cycles.

PMID- 25603144
TI  - The extraction process optimization of antioxidant polysaccharides from
      Marshmallow (Althaea officinalis L.) roots.
AB  - Response surface methodology (RSM) with a central composite rotatable design
      (CCRD) based on five levels was employed to model and optimize four experimental
      operating conditions of extraction temperature (10-90  degrees C) and time (6-30
      h), particle size (6-24 mm) and water to solid (W/S, 10-50) ratio, obtaining
      polysaccharides from Althaea officinalis roots with high yield and antioxidant
      activity. For each response, a second-order polynomial model with high R(2)
      values (> 0.966) was developed using multiple linear regression analysis. Results
      showed that the most significant (P < 0.05) extraction conditions that affect the
      yield and antioxidant activity of extracted polysaccharides were the main effect
      of extraction temperature and the interaction effect of the particle size and W/S
      ratio. The optimum conditions to maximize yield (10.80%) and antioxidant activity
      (84.09%) for polysaccharides extraction from A. officinalis roots were extraction
      temperature 60.90  degrees C, extraction time 12.01 h, particle size 12.0mm and
      W/S ratio of 40.0. The experimental values were found to be in agreement with
      those predicted, indicating the models suitability for optimizing the
      polysaccharides extraction conditions.

PMID- 25603145
TI  - Ag(0) nanoparticles containing cotton fabric: Synthesis, characterization, color
      data and antibacterial action.
AB  - The main objective of the current research was to successfully employ the
      reducing and stabilizing features of xanthan gum to synthesize nanosilver, then
      coating cotton fabrics with the net produced nanosilver in order to obtain
      finished fabrics valuable in medical applications. Pre-hydrolyzed xanthan gum was
      used to reduce Ag(+) to Ag(0) in nano size using a simple one-step rapid
      synthetic route. The reduction step was followed up by measuring the
      concentration of reducing sugars eliminated in the reaction medium. The optimum
      concentration of xanthan gum was 3g/L to reduce 1 mmol/L Ag(+), as 2.66 +/- 0.4
      g/L was the maximum concentration of reducing sugars obtained in the reaction.
      Transmission microscope images show that the AgNPs are spherical in shape with
      mean size 9.1 +/- 4.8 nm. Cotton fabrics were then coated with the produced AgNPs
      using pad-dry-cure method. Well dispersed layer from Ag(0) on cotton surface was
      showed under electron microscope. The biocidal activities of the coated fabrics
      were tested against Staphylococcus aureus and showed excellent results for
      antibacterial even after 20 washing cycles. This method has the advantage of not
      necessitating aggressive conditions such as the presence of organic solvents to
      produce durable antibacterial cotton fabrics.

PMID- 25603146
TI  - Structure of KRT4 binding domain of Srr-1 from Streptococcus agalactiae reveals a
      novel beta-sheet complementation.
AB  - The serine rich repeat protein-1 (Srr-1) is an adhesive protein of Streptococcus
      agalactiae. It is the first bacterial protein identified to interact with human
      keratin 4 (K4 or KRT4). Within Srr-1, the residues 311-641 constitute the non
      repeat ligand binding region (Srr-1-BR(311-641)). The C-terminal part of Srr-1
      BR(311-641), comprising of residues 485-642 (termed Srr-1-K4BD), have been
      identified to bind to K4. Here we report the crystal structure of recombinant Srr
      1-K4BD(485-642) and its possible mode of interaction with K4 through docking
      studies. The dimeric structure of Srr-1-K4BD(485-642) reveals a novel two way
      "slide lock" parallel beta-sheet complementation where the C-terminal strand of
      one monomer is positioned anti-parallel to the N-terminal strand of the adjacent
      monomer and this arrangement is not seen so far in any of the homologous
      structures. The dimerization of Srr-1-K4BD(485-642) observed both in the crystal
      structure and in solution suggests that similar domain association could also be
      possible in in vivo and we propose this association would likely generate a new
      binding site for another host molecule. It is likely that the adhesin can
      recognize multiple ligands using its ligand binding sub-domains through their
      intra and inter domain association with one another.

PMID- 25603147
TI  - Ultrasonic and free-radical degradation of mannan from Candida albicans.
AB  - Mannan from pathogenic Candida albicans serotype A was degraded by means of
      ultrasound and/or OH generated in situ by Fenton reaction. The kinetics of
      degradation was monitored by HPLC analysis and the weight-average molecular
      weights (Mw) and index of polydispersity (PDI) were compared. A well-defined low
      molecular-weight mannan (~ 30 kDa) with narrowed PDI of 1.8 was obtained after
      120 min of ultrasonication. Similar or even lower Mw (up to 16 kDa) was achieved
      upon free-radical exposure depending on Fe(2+) concentration used; however, this
      was accompanied by overall broadening of PDI and distinct changes in polymer
      structure as indicated by NMR analysis.

PMID- 25603148
TI  - Preparation Fe3O4@chitosan magnetic particles for covalent immobilization of
      lipase from Thermomyces lanuginosus.
AB  - Magnetic Fe3O4@chitosan nanoparticles were prepared by a simple in situ co
      precipitation method and characterized by transmission electron microscope (TEM)
      and Fourier transform infrared spectroscopy (FTIR). The prepared Fe3O4@chitosan
      nanoparticles were used for covalent immobilization of lipase from Thermomyces
      lanuginosus by chemical conjugation after electrostatic entrapment (CCEE). The
      optimal immobilization conditions were obtained as follows: enzyme/support 19.8
      mg/g, pH 5.0, time 4h and temperature 30  degrees C. Under these conditions, a
      high immobilization efficiency of 75% and a protein loading of 16.8 mg/g-support
      were obtained. Broad pH tolerance and high thermostability could be achieved by
      immobilization. The immobilized lipase retained 70% initial activity after ten
      cycles. Kinetic parameters Vmax and Km of free and immobilized lipase were
      determined as 5.72 mM/min, 2.26 mM/min and 21.25 mM, 28.73 mM, respectively.
      Ascorbyl palmitate synthesis with immobilized lipase was carried out in tert
      butanol at 50  degrees C, and the conversion of ascorbic acid was obtained higher
      than 50%. These results showed that the immobilization of lipase onto magnetic
      chitosan nanoparticles by the method of CCEE is an efficient and simple way for
      preparation of stable lipase.

PMID- 25603149
TI  - Metagenomics shows that low-energy anaerobic-aerobic treatment reactors reduce
      antibiotic resistance gene levels from domestic wastewater.
AB  - Effective domestic wastewater treatment is among our primary defenses against the
      dissemination of infectious waterborne disease. However, reducing the amount of
      energy used in treatment processes has become essential for the future. One low
      energy treatment option is anaerobic-aerobic sequence (AAS) bioreactors, which
      use an anaerobic pretreatment step (e.g., anaerobic hybrid reactors) to reduce
      carbon levels, followed by some form of aerobic treatment. Although AAS is common
      in warm climates, it is not known how its compares to other treatment options
      relative to disease transmission, including its influence on antibiotic
      resistance (AR) in treated effluents. Here, we used metagenomic approaches to
      contrast the fate of antibiotic-resistant genes (ARG) in anaerobic, aerobic, and
      AAS bioreactors treating domestic wastewater. Five reactor configurations were
      monitored for 6 months, and treatment performance, energy use, and ARG abundance
      and diversity were compared in influents and effluents. AAS and aerobic reactors
      were superior to anaerobic units in reducing ARG-like sequence abundances, with
      effluent ARG levels of 29, 34, and 74 ppm (198 ppm influent), respectively. AAS
      and aerobic systems especially reduced aminoglycoside, tetracycline, and beta
      lactam ARG levels relative to anaerobic units, although 63 persistent ARG
      subtypes were detected in effluents from all systems (of 234 assessed).
      Sulfonamide and chloramphenicol ARG levels were largely unaffected by treatment,
      whereas a broad shift from target-specific ARGs to ARGs associated with multi
      drug resistance was seen across influents and effluents. AAS reactors show
      promise for future applications because they can reduce more ARGs for less energy
      (32% less energy here), but all three treatment options have limitations and need
      further study. 

PMID- 25603150
TI  - The deletion of rnhB in Mycobacterium smegmatis does not affect the level of
      RNase HII substrates or influence genome stability.
AB  - RNase HII removes RNA from RNA/DNA hybrids, such as single ribonucleotides and
      RNA primers generated during DNA synthesis. Both, RNase HII substrates and RNase
      HII deficiency have been associated with genome instability in several organisms,
      and genome instability is a major force leading to the acquisition of drug
      resistance in bacteria. Understanding the mechanisms that underlie this
      phenomenon is one of the challenges in identifying efficient methods to combat
      bacterial pathogens. The aim of the present study was set to investigate the role
      of rnhB, presumably encoding RNase HII, in maintaining genome stability in the M.
      tuberculosis model organism Mycobacterium smegmatis. We performed gene
      replacement through homologous recombination to obtain mutant strains of
      Mycobacterium smegmatis lacking the rnhB gene. The mutants did not present an
      altered phenotype, according to the growth rate in liquid culture or
      susceptibility to hydroxyurea, and did not show an increase in the spontaneous
      mutation rate, determined using the Luria-Delbruck fluctuation test for
      streptomycin resistance in bacteria. The mutants also did not present an increase
      in the level of RNase HII substrates, measured as the level of alkaline
      degradation of chromosomal DNA or determined through immunodetection. We conclude
      that proteins other than RnhB proteins efficiently remove RNase HII substrates in
      M. smegmatis. These results highlight differences in the basic biology between
      Mycobacteria and eukaryotes and between different species of bacteria. 

PMID- 25603152
TI  - A one-pot direct iodination of the Fischer-Borsche ring using molecular iodine
      and its utility in the synthesis of 6-oxygenated carbazole alkaloids.
AB  - An efficient regioselective iodination of the Fischer-Borsche ring has been
      achieved using molecular iodine, in a one-pot synthesis. The acid-, metal-, and
      oxidant-free conditions of the present method are highly convenient and
      practical. Furthermore, the one-pot direct iodination process is extended to the
      concise synthesis of glycozoline, 3-formyl-6-methoxy-carbazole, and 6-methoxy
      carbazole-3-methylcarboxylate natural alkaloids. This method has been proven to
      be tolerant to a broad range of functional groups, with good to excellent yields.

PMID- 25603151
TI  - Gene therapy studies in a canine model of X-linked severe combined
      immunodeficiency.
AB  - Since the occurrence of T cell leukemias in the original human gamma-retroviral
      gene therapy trials for X-linked severe combined immunodeficiency (XSCID),
      considerable effort has been devoted to developing safer vectors. This review
      summarizes gene therapy studies performed in a canine model of XSCID to evaluate
      the efficacy of gamma-retroviral, lentiviral, and foamy viral vectors for
      treating XSCID and a novel method of vector delivery. These studies demonstrate
      that durable T cell reconstitution and thymopoiesis with no evidence of any
      serious adverse events and, in contrast to the human XSCID patients, sustained
      marking in myeloid cells and B cells with reconstitution of normal humoral immune
      function can be achieved for up to 5 years without any pretreatment conditioning.
      The presence of sustained levels of gene-marked T cells, B cells, and more
      importantly myeloid cells for almost 5 years is highly suggestive of transduction
      of either multipotent hematopoietic stem cells or very primitive committed
      progenitors. 

PMID- 25603153
TI  - Tramadol-related psychosis in a patient with bipolar I disorder.
AB  - INTRODUCTION: Tramadol hydrochloride (HCl) is a centrally acting synthetic opioid
      analgesic. Psychotic symptoms are relatively rare in reported adverse events.
      Here, we report a patient who presented with tramadol-related psychotic symptoms.
      CASE: A 59-year-old female had underlying bipolar I disorder and received lithium
      treatment with stable affective status. 1 month before hospitalisation, she had
      been taking tramadol HCl/acetaminophen for joint pain. She then developed obvious
      persecutory delusion. However, her clinical picture did not meet the criteria of
      any mood episode. After treatment of risperidone in addition to lithium, she was
      discharged without any psychotic symptom. She remained euthymic without any
      psychotic symptom on monotherapy of lithium (300 mg) three tablets once daily.
      CONCLUSIONS: Tramadol HCl is commonly prescribed in clinical practice and
      psychotic symptoms related to it are uncommon. We should be careful about the
      rare but important adverse events while prescribing tramadol HCl.

PMID- 25603154
TI  - Succession of microbial functional communities in response to a pilot-scale
      ethanol-blended fuel release throughout the plume life cycle.
AB  - GeoChip, a comprehensive gene microarray, was used to examine changes in
      microbial functional gene structure throughout the 4-year life cycle of a pilot
      scale ethanol blend plume, including 2-year continuous released followed by plume
      disappearance after source removal. Canonical correlation analysis (CCA) and
      Mantel tests showed that dissolved O2 (which was depleted within 5 days of
      initiating the release and rebounded 194 days after source removal) was the most
      influential environmental factor on community structure. Initially, the abundance
      of anaerobic BTEX degradation genes increased significantly while that of aerobic
      BTEX degradation genes decreased. Gene abundance for N fixation, nitrification, P
      utilization, sulfate reduction and S oxidation also increased, potentially
      changing associated biogeochemical cycle dynamics. After plume disappearance,
      most genes returned to pre-release abundance levels, but the final functional
      structure significantly differed from pre-release conditions. Overall, observed
      successions of functional structure reflected adaptive responses that were
      conducive to biodegradation of ethanol-blend releases. 

PMID- 25603155
TI  - The effects of lead sources on oral bioaccessibility in soil and implications for
      contaminated land risk management.
AB  - Lead (Pb) is a non-threshold toxin capable of inducing toxic effects at any blood
      level but availability of soil screening criteria for assessing potential health
      risks is limited. The oral bioaccessibility of Pb in 163 soil samples was
      attributed to sources through solubility estimation and domain identification.
      Samples were extracted following the Unified BARGE Method. Urban, mineralisation,
      peat and granite domains accounted for elevated Pb concentrations compared to
      rural samples. High Pb solubility explained moderate-high gastric (G)
      bioaccessible fractions throughout the study area. Higher maximum G
      concentrations were measured in urban (97.6 mg kg(-1)) and mineralisation (199.8
      mg kg(-1)) domains. Higher average G concentrations occurred in mineralisation
      (36.4 mg kg(-1)) and granite (36.0 mg kg(-1)) domains. Findings suggest diffuse
      anthropogenic and widespread geogenic contamination could be capable of
      presenting health risks, having implications for land management decisions in
      jurisdictions where guidance advises these forms of pollution should not be
      regarded as contaminated land.

PMID- 25603157
TI  - Chemical and anatomical changes in Liquidambar styraciflua L. xylem after long
      term exposure to elevated CO2.
AB  - The anatomical and chemical characteristics of sweetgum were studied after 11
      years of elevated CO2 (544 ppm, ambient at 391 ppm) exposure. Anatomically,
      branch xylem cells were larger for elevated CO2 trees, and the cell wall
      thickness was thinner. Chemically, elevated CO2 exposure did not impact the
      structural components of the stem wood, but non-structural components were
      significantly affected. Principal component analysis (PCA) was employed to detect
      differences between the CO2 treatments by considering numerous structural and
      chemical variables, as well as tree size, and data from previously published
      sources (i.e., root biomass, production and turnover). The PCA results indicated
      a clear separation between trees exposed to ambient and elevated CO2 conditions.
      Correlation loadings plots of the PCA revealed that stem structural components,
      ash, Ca, Mg, total phenolics, root biomass, production and turnover were the
      major responses that contribute to the separation between the elevated and
      ambient CO2 treated trees.

PMID- 25603156
TI  - Occurrence and spatial distribution of organophosphate ester flame retardants and
      plasticizers in 40 rivers draining into the Bohai Sea, north China.
AB  - Organophosphate esters (OPEs) are alternatives to polybrominated diphenyl ethers,
      often used as flame-retardants and plasticizers. There are few reports of OPEs in
      river water. This study focused on the occurrence and spatial distribution of 11
      OPE congeners and one synthetic intermediate triphenylphosphine oxide (TPPO) in
      40 major rivers entering into the Bohai Sea. Total OPEs ranged from 9.6 to 1549
      ng L(-1), with an average of 300 ng L(-1). Tris(1-chloro-2-propyl) phosphate
      (TCPP) (4.6-921 ng L(-1), mean: 186 ng L(-1)) and tris(2-choroethyl) phosphate
      (TCEP) (1.3-268 ng L(-1), mean: 80.2 ng L(-1)) were the most abundant OPEs and
      their distribution patterns are similar, indicating the same source (r = 0.61, P
      < 0.05) and the influence of large production and consumption of chlorinated OPEs
      in the region. Priority should be given to TCPP, PCEP and TPPO due to their high
      concentrations in the rivers and potential threat to aquatic organisms.

PMID- 25603158
TI  - Parameter estimation of fractional-order chaotic systems by using quantum
      parallel particle swarm optimization algorithm.
AB  - Parameter estimation for fractional-order chaotic systems is an important issue
      in fractional-order chaotic control and synchronization and could be essentially
      formulated as a multidimensional optimization problem. A novel algorithm called
      quantum parallel particle swarm optimization (QPPSO) is proposed to solve the
      parameter estimation for fractional-order chaotic systems. The parallel
      characteristic of quantum computing is used in QPPSO. This characteristic
      increases the calculation of each generation exponentially. The behavior of
      particles in quantum space is restrained by the quantum evolution equation, which
      consists of the current rotation angle, individual optimal quantum rotation
      angle, and global optimal quantum rotation angle. Numerical simulation based on
      several typical fractional-order systems and comparisons with some typical
      existing algorithms show the effectiveness and efficiency of the proposed
      algorithm. 

PMID- 25603162
TI  - Slow magnetization relaxation in Ni(II)Dy(III)Fe(III) molecular cycles.
AB  - Two cyano- and phenoxo-bridged hexanuclear Ni(II)2Dy(III)2Fe(III)2 (1) and
      octanuclear Ni(II)4Dy(III)2Fe(III)2 (2) trimetallic cyclic complexes have been
      obtained. They are the first trimetallic metallocycles. Magnetic studies reveal
      that 1 and 2 exhibit single-molecule-magnet behavior with an energy barrier of
      17.9 K for complex 1 in a 2000 Oe static field and 25.0 K for complex 2 in a zero
      static field. 

PMID- 25603159
TI  - The EPCOR model: a model for promoting the successful implementation of evidence
      based nursing in hospital-based settings.
AB  - BACKGROUND: An effective organizational infrastructure is essential to
      successfully implement and sustain an evidence-based nursing (EBN) practice.
      Although EBN has been promoted in Taiwan for more than 10 years, variations in
      the organizational policies and strategies necessary to support EBN among
      healthcare organizations have prevented effective implementation. Barriers to the
      implementation of EBN located at the organizational level have also been
      reported. The need for a model that focuses on the organizational infrastructure
      to promote EBN in Taiwan has therefore become increasingly apparent. PURPOSE:
      This study aims to develop a model that contains the key contextual elements of
      organizational infrastructure necessary to effectively promote EBN, especially in
      hospital settings. METHODS: A steering committee drafted the components and
      related strategies of the proposed model. Delphi technique was used to obtain
      consensus on the proposed model among a group of experts with expertise in EBN.
      Thirty experts participated in all three rounds of the Delphi survey. To confirm
      the appropriateness of the proposed model for clinical settings, the model was
      further reviewed by a focus group composed of experts with experience in
      implementing EBN or evidence-based medicine in hospitals. The strategies were
      then further modified based on the suggestions of this focus group, and only
      those strategies that best fit hospital settings were retained. RESULTS: Five key
      contextual elements and related strategic processes were identified, including
      equipment, policy, training courses, outcome indicators, and reward plans. The
      resultant model was named EPCOR, an acronym composed of the names of each
      identified element. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: EPCOR is a
      comprehensive model of organizational infrastructure and strategic procedures for
      implementing EBN in hospital-based settings in Taiwan. Organizations may use the
      EPCOR model to initiate and implement EBN practices and then to evaluate their
      effectiveness.

PMID- 25603163
TI  - Ultra-low-dose estradiol and norethisterone acetate: bleeding patterns and other
      outcomes over 52 weeks of therapy.
AB  - BACKGROUND: Continuous combined hormone replacement therapy (HRT) with 0.5 mg
      17beta-estradiol (E2) + 0.1 mg norethisterone acetate (NETA) received marketing
      approval based on 24-week results. The current study collected data up to 52
      weeks, including consideration of bleeding, a major reason for stopping HRT.
      METHODS: This 52-week (13 lunar-month), non-interventional, prospective study
      involved 169 women from Norway and Sweden receiving daily oral 0.5 mg E2 + 0.1 mg
      NETA to treat menopausal symptoms. Incidences and cumulative rates of amenorrhea
      (no bleeding or spotting) and no bleeding (women could have spotting) were
      evaluated, together with hot flushes and quality of life. RESULTS: Overall, > 78%
      and > 90% of subjects were amenorrheic or had no bleeding, respectively, in each
      of the first 3 lunar months, while > 88% and > 96% were amenorrheic or had no
      bleeding, respectively, in each of lunar months 10, 11 and 12. Cumulative rates
      of amenorrhea and no bleeding were 67% and 83%, respectively, in lunar months 1
      3, and 84% and 94%, respectively, in lunar months 10-12. The number of hot
      flushes declined during treatment (means at weeks 1, 12 and 52, respectively:
      15.5, 5.0 and 4.1 [mild]; 19.0, 3.0 and 2.3 [moderate]; 10.8, 1.1 and 0.9
      [severe]). Improvement in all four domains of the Menopause-Specific Quality of
      Life-Intervention questionnaire (vasomotor, psychosocial, physical and sexual)
      was evident by week 26. CONCLUSION: For women receiving 0.5 mg E2 + 0.1 mg NETA,
      lack of bleeding-related side-effects, together with beneficial effects on hot
      flush symptoms and quality of life, may promote treatment continuance.

PMID- 25603164
TI  - GHSR hypermethylation: a promising pan-cancer marker.

PMID- 25603165
TI  - Hierarchical Bayesian models of subtask learning.
AB  - The current study used Bayesian hierarchical methods to challenge and extend
      previous work on subtask learning consistency. A general model of individual
      level subtask learning was proposed focusing on power and exponential functions
      with constraints to test for inconsistency. To study subtask learning, we
      developed a novel computer-based booking task, which logged participant actions,
      enabling measurement of strategy use and subtask performance. Model comparison
      was performed using deviance information criterion (DIC), posterior predictive
      checks, plots of model fits, and model recovery simulations. Results showed that
      although learning tended to be monotonically decreasing and decelerating, and
      approaching an asymptote for all subtasks, there was substantial inconsistency in
      learning curves both at the group- and individual-levels. This inconsistency was
      most apparent when constraining both the rate and the ratio of learning to
      asymptote to be equal across subtasks, thereby giving learning curves only 1
      parameter for scaling. The inclusion of 6 strategy covariates provided improved
      prediction of subtask performance capturing different subtask learning processes
      and subtask trade-offs. In addition, strategy use partially explained the
      inconsistency in subtask learning. Overall, the model provided a more nuanced
      representation of how complex tasks can be decomposed in terms of simpler
      learning mechanisms.

PMID- 25603166
TI  - The contribution of encoding and retrieval processes to proactive interference.
AB  - Proactive interference (PI) refers to the finding that memory for recently
      studied (target) material can be impaired by the prior study of other (nontarget)
      material. Previous accounts of PI differed in whether they attributed PI to
      impaired retrieval or impaired encoding. Here, we suggest an integrated encoding
      retrieval account, which assigns a role for each of the 2 types of processes in
      buildup of PI. Employing a typical PI task, we examined (a) the role of encoding
      processes in PI by recording scalp EEG during study of nontarget and target
      lists, and (b) the role of retrieval processes in PI by measuring recall totals
      and response latencies in target list recall. In addition, we measured subjects'
      working memory capacity (WMC). Behaviorally, the PI effect arose in both recall
      totals and response latencies, indicating PI at the sampling and the recovery
      stage of recall. Neurally, we found an increase in electrophysiological
      activities in the theta frequency band (5-8 Hz) from nontarget to target list
      encoding, indicating an increase in memory load during target list encoding. The
      results demonstrate that impaired retrieval and impaired encoding can contribute
      to PI. They also show that WMC affects PI. For both encoding and retrieval
      processes, PI was reduced in high-WMC subjects, suggesting that these subjects
      are able to separate target from nontarget information and create stronger focus
      on the target material.

PMID- 25603167
TI  - Deductive updating is not Bayesian.
AB  - One of the major debates concerning the nature of inferential reasoning is
      between counterexample-based theories such as mental model theory and
      probabilistic theories. This study looks at conclusion updating after the
      addition of statistical information to examine the hypothesis that deductive
      reasoning cannot be explained by probabilistic inferences. In Study 1,
      participants were given an initial "If P then Q rule" for a phenomenon on a
      recently discovered planet, told that "Q was true," and asked to make a judgment
      of either deductive validity or probabilistic likelihood of the putative
      conclusion that "P is true." They were then told the results of 1,000
      observations. In the low-probability problem, 950 times P was false and Q was
      true, whereas 50 times P was true and Q was true. In the high-probability
      problem, these proportions were inverted. On the low-probability problem,
      probabilistic ratings and judgments of logical validity decreased. However, on
      the high-probability problem, probabilistic ratings remained high whereas
      judgments of logical validity significantly decreased. Confidence ratings were
      consistent with this different pattern for probabilistic and for deductive
      inferences. Study 2 replicated this result with another form of inference, "If P
      then Q. P is false." These results show that deductive updating is not explicable
      by Bayesian updating.

PMID- 25603168
TI  - Event structure and cognitive control.
AB  - Recently, a great deal of research has demonstrated that although everyday
      experience is continuous in nature, it is parsed into separate events. The aim of
      the present study was to examine whether event structure can influence the
      effectiveness of cognitive control. Across 5 experiments we varied the structure
      of events within the AX-CPT by shifting the spatial location of cues and probes
      on a computer screen. When location shifts were present, a pattern of AX-CPT
      performance consistent with enhanced cognitive control was found. To test whether
      the location shift effects were caused by the presence of event boundaries per
      se, other aspects of the AX-CPT were manipulated, such as the color of cues and
      probes and the inclusion of a distractor task during the cue-probe delay. Changes
      in cognitive control were not found under these conditions, suggesting that the
      location shift effects were specifically related to the formation of separate
      event models. Together, these results can be accounted for by the Event Horizon
      Model and a representation-based theory of cognitive control, and suggest that
      cognitive control can be influenced by the surrounding environmental structure.

PMID- 25603170
TI  - Effect of H2 binding on the nonadiabatic transition probability between singlet
      and triplet states of the [NiFe]-hydrogenase active site.
AB  - We investigate the effect of H2 binding on the spin-forbidden nonadiabatic
      transition probability between the lowest energy singlet and triplet electronic
      states of [NiFe]-hydrogenase active site model, using a velocity averaged Landau
      Zener theory. Density functional and multireference perturbation theories were
      used to provide parameters for the Landau-Zener calculations. It was found that
      variation of the torsion angle between the terminal thiolate ligands around the
      Ni center induces an intersystem crossing between the lowest energy singlet and
      triplet electronic states in the bare active site and in the active site with
      bound H2. Potential energy curves between the singlet and triplet minima along
      the torsion angle and H2 binding energies to the two spin states were calculated.
      Upon H2 binding to the active site, there is a decrease in the torsion angle at
      the minimum energy crossing point between the singlet and triplet states. The
      probability of nonadiabatic transitions at temperatures between 270 and 370 K
      ranges from 35% to 32% for the active site with bound H2 and from 42% to 38% for
      the bare active site, thus indicating the importance of spin-forbidden
      nonadiabatic pathways for H2 binding on the [NiFe]-hydrogenase active site. 

PMID- 25603169
TI  - Cloning and characterization of a Weissella confusa dextransucrase and its
      application in high fibre baking.
AB  - Wheat bran offers health benefits as a baking ingredient, but is detrimental to
      bread textural quality. Dextran production by microbial fermentation improves
      sourdough bread volume and freshness, but extensive acid production during
      fermentation may negate this effect. Enzymatic production of dextran in wheat
      bran was tested to determine if dextran-containing bran could be used in baking
      without disrupting bread texture. The Weissella confusa VTT E-90392
      dextransucrase gene was sequenced and His-tagged dextransucrase Wc392-rDSR was
      produced in Lactococcus lactis. Purified enzyme was characterized using (14)C
      sucrose radioisotope and reducing value-based assays, the former yielding K(m)
      and V(max) values of 14.7 mM and 8.2 MUmol/(mg ? min), respectively, at the pH
      optimum of 5.4. The structure and size of in vitro dextran product was similar to
      dextran produced in vivo. Dextran (8.1% dry weight) was produced in wheat bran in
      6 h using Wc392-rDSR. Bran with and without dextran was used in wheat baking at
      20% supplementation level. Dextran presence improved bread softness and
      neutralized bran-induced volume loss, clearly demonstrating the potential of
      using dextransucrases in bran bioprocessing for use in baking.

PMID- 25603171
TI  - Conformational nanobodies reveal tethered epidermal growth factor receptor
      involved in EGFR/ErbB2 predimers.
AB  - The epidermal growth factor receptor (EGFR) is a cell-surface receptor with a
      single transmembrane domain and tyrosine kinase activity carried by the
      intracellular domain. This receptor is one of the four members of the ErbB family
      including ErbB2, ErbB3, and ErbB4. Ligand binding, like EGF binding, induces a
      conformational rearrangement of the receptor and induces a homo/hetero
      dimerization essentially with ErbB family receptors that leads to the
      phosphorylation of the kinase domain, triggering a signaling cascade. EGFR can
      also form inactive dimers in a ligand-independent way through interactions
      between cytoplasmic domains. To date, the conformation of EGFR extracellular
      domain engaged in these inactive dimers remains unclear. In this study, we
      describe the successful selection and characterization of llama anti-EGFR
      nanobodies and their use as innovative conformational sensors. We isolated three
      different specific anti-EGFR clones binding to three distinct epitopes.
      Interestingly, the binding of all three nanobodies was found highly sensitive to
      ligand stimulation. Two nanobodies, D10 and E10, can only bind the ligand-free
      EGFR conformation characterized by an intramolecular tether between domains II
      and IV, whereas nanobody G10 binds both ligand-free and ligand activated EGFR,
      with an 8-fold higher affinity for the extended conformation in the presence of
      ligand. Here we took advantage of these conformational probes to reveal the
      existence of tethered EGFR in EGFR/ErbB2 predimers. These biosensors represent
      important tools allowing the determination of EGFR conformations and should help
      the design of relevant inhibitors. 

PMID- 25603172
TI  - Copper(I)-taniaphos catalyzed enantiodivergent hydroboration of bicyclic alkenes.
AB  - In this study, highly enantioselective copper(I)-catalyzed hydroboration of
      bicyclic alkenes is reported. Using a copper-taniaphos complex, excellent
      enantioselectivities up to >99% ee were obtained for bicyclic alkenes including
      oxa- and azabicyclic alkenes. Furthermore, copper-catalyzed enantiodivergent
      hydroboration methods with the same chiral ligand-copper precursors were
      developed using different boron sources based on alternative mechanistic
      pathways. 

PMID- 25603173
TI  - Reply to the Comment on "Structural characterization of dissolved organic matter:
      a review of current techniques for isolation and analysis" by E. C. Minor, M. M.
      Swenson, B. M. Mattson, and A. R. Oyler, Environ. Sci.: Processes Impacts, 2014,
      16, 2064.

PMID- 25603174
TI  - Phytotoxic eremophilane sesquiterpenes from the coprophilous fungus Penicillium
      sp. G1-a14.
AB  - Bioassay-directed fractionation of an extract from the grain-based culture of the
      coprophilous fungus Penicillium sp. G1-a14 led to the isolation of a new
      eremophilane-type sesquiterpene, 3R,6R-dihydroxy-9,7(11)-dien-8-oxoeremophilane
      (1), along with three known analogues, namely, isopetasol (2), sporogen AO-1 (3),
      and dihydrosporogen AO-1 (4). The structure of 1 was elucidated using 1D and 2D
      NMR and single-crystal X-ray diffraction. Assignment of absolute configuration at
      the stereogenic centers of 1 was achieved using ECD spectroscopy combined with
      time-dependent density functional theory calculations. Sporogen AO-1 (3) and
      dihydrosporogen AO-1 (4) caused significant inhibition of radicle growth against
      Amaranthus hypochondriacus (IC50 = 0.17 mM for both compounds) and Echinochloa
      crus-galli (IC50 = 0.17 and 0.30 mM, respectively). 

PMID- 25603175
TI  - Minority stress and binge eating among lesbian and bisexual women.
AB  - Previous research demonstrates that lesbian and bisexual (LB) women report more
      binge eating behaviors compared to heterosexual women although the explanations
      for this disparity are not well understood. LB women also experience distal
      (e.g., discrimination) and proximal (e.g., expectations of rejection) minority
      stressors that are related to negative mental and physical health outcomes. The
      present study investigated the association between minority stressors and binge
      eating behaviors in LB women. A sample of 164 LB women completed an online survey
      that included measures of distal and proximal sexual minority stressors,
      emotional-focused coping, social isolation, negative affect, and binge eating.
      The resultant model partially supported both the psychological mediation
      framework and the affect regulation model. The principal finding was that among
      LB women, proximal stressors were associated with social isolation and emotion
      focused coping, which in turn were associated with negative affect and ultimately
      binge eating. Overall, the study provides evidence that minority stress is
      associated with binge eating and may partially explain the disparity in binge
      eating between LB and heterosexual women. 

PMID- 25603176
TI  - Melatonin stimulates dendrite formation and complexity in the hilar zone of the
      rat hippocampus: participation of the Ca++/Calmodulin complex.
AB  - Melatonin (MEL), the main product synthesized by the pineal gland, stimulates
      early and late stages of neurodevelopment in the adult brain. MEL increases
      dendrite length, thickness and complexity in the hilar and mossy neurons of
      hippocampus. Dendrite formation involves activation of Ca2+/Calmodulin (CaM)
      dependent kinase II (CaMKII) by CaM. Previous work showed that MEL increased the
      synthesis and translocation of CaM, suggesting that MEL activates CaM-dependent
      enzymes by this pathway. In this work we investigated whether MEL stimulates
      dendrite formation by CaMKII activation in organotypic cultures from adult rat
      hippocampus. We found that the CaMKII inhibitor, KN-62, abolished the MEL
      stimulatory effects on dendritogenesis and that MEL increased the relative amount
      of CaM in the soluble fraction of hippocampal slices. Also, PKC inhibition
      abolished dendritogenesis, while luzindole, an antagonist of MEL receptors
      (MT1/2), partially blocked the effects of MEL. Moreover, autophosphorylation of
      CaMKII and PKC was increased in presence of MEL, as well as phosphorylation of
      ERK1/2. Our results indicate that MEL stimulates dendrite formation through
      CaMKII and the translocation of CaM to the soluble fraction. Dendritogenesis
      elicited by MEL also required PKC activation, and signaling through MT1/2
      receptors was partially involved. Data strongly suggest that MEL could repair the
      loss of hippocampal dendrites that occur in neuropsychiatric disorders by
      increasing CaM levels and activation of CaMKII. 

PMID- 25603177
TI  - BRD4 inhibitor inhibits colorectal cancer growth and metastasis.
AB  - Post-translational modifications have been identified to be of great importance
      in cancers and lysine acetylation, which can attract the multifunctional
      transcription factor BRD4, has been identified as a potential therapeutic target.
      In this paper, we identify that BRD4 has an important role in colorectal cancer;
      and that its inhibition substantially wipes out tumor cells. Treatment with
      inhibitor MS417 potently affects cancer cells, although such effects were not
      always outright necrosis or apoptosis. We report that BRD4 inhibition also limits
      distal metastasis by regulating several key proteins in the progression of
      epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is
      demonstrated via liver metastasis in animal model as well as migration and
      invasion experiments in vitro. Together, our results demonstrate a new
      application of BRD4 inhibitor that may be of clinical use by virtue of its
      ability to limit metastasis while also being tumorcidal. 

PMID- 25603180
TI  - Meshless method with operator splitting technique for transient nonlinear bioheat
      transfer in two-dimensional skin tissues.
AB  - A meshless numerical scheme combining the operator splitting method (OSM), the
      radial basis function (RBF) interpolation, and the method of fundamental
      solutions (MFS) is developed for solving transient nonlinear bioheat problems in
      two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity
      caused by linear and exponential relationships of temperature-dependent blood
      perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is
      used first to separate the Laplacian operator and the nonlinear source term, and
      then the second-order time-stepping schemes are employed for approximating two
      splitting operators to convert the original governing equation into a linear
      nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step.
      Subsequently, the RBF interpolation and the MFS involving the fundamental
      solution of the Laplace equation are respectively employed to obtain approximated
      particular and homogeneous solutions of the nonhomogeneous Helmholtz-type
      governing equation. Finally, the full fields consisting of the particular and
      homogeneous solutions are enforced to fit the NHGE at interpolation points and
      the boundary conditions at boundary collocations for determining unknowns at each
      time step. The proposed method is verified by comparison of other methods.
      Furthermore, the sensitivity of the coefficients in the cases of a linear and an
      exponential relationship of TDBPR is investigated to reveal their bioheat effect
      on the skin tissue. 

PMID- 25603178
TI  - Ligand-induced dynamics of neurotrophin receptors investigated by single-molecule
      imaging approaches.
AB  - Neurotrophins are secreted proteins that regulate neuronal development and
      survival, as well as maintenance and plasticity of the adult nervous system. The
      biological activity of neurotrophins stems from their binding to two membrane
      receptor types, the tropomyosin receptor kinase and the p75 neurotrophin
      receptors (NRs). The intracellular signalling cascades thereby activated have
      been extensively investigated. Nevertheless, a comprehensive description of the
      ligand-induced nanoscale details of NRs dynamics and interactions spanning from
      the initial lateral movements triggered at the plasma membrane to the
      internalization and transport processes is still missing. Recent advances in high
      spatio-temporal resolution imaging techniques have yielded new insight on the
      dynamics of NRs upon ligand binding. Here we discuss requirements, potential and
      practical implementation of these novel approaches for the study of neurotrophin
      trafficking and signalling, in the framework of current knowledge available also
      for other ligand-receptor systems. We shall especially highlight the correlation
      between the receptor dynamics activated by different neurotrophins and the
      respective signalling outcome, as recently revealed by single-molecule tracking
      of NRs in living neuronal cells. 

PMID- 25603181
TI  - Designed surface residue substitutions in [NiFe] hydrogenase that improve
      electron transfer characteristics.
AB  - Photobiological hydrogen production is an attractive, carbon-neutral means to
      convert solar energy to hydrogen. We build on previous research improving the
      Alteromonas macleodii "Deep Ecotype" [NiFe] hydrogenase, and report progress
      towards creating an artificial electron transfer pathway to supply the
      hydrogenase with electrons necessary for hydrogen production. Ferredoxin is the
      first soluble electron transfer mediator to receive high-energy electrons from
      photosystem I, and bears an electron with sufficient potential to efficiently
      reduce protons. Thus, we engineered a hydrogenase-ferredoxin fusion that also
      contained several other modifications. In addition to the C-terminal ferredoxin
      fusion, we truncated the C-terminus of the hydrogenase small subunit, identified
      as the available terminus closer to the electron transfer region. We also
      neutralized an anionic patch surrounding the interface Fe-S cluster to improve
      transfer kinetics with the negatively charged ferredoxin. Initial screening
      showed the enzyme tolerated both truncation and charge neutralization on the
      small subunit ferredoxin-binding face. While the enzyme activity was relatively
      unchanged using the substrate methyl viologen, we observed a marked improvement
      from both the ferredoxin fusion and surface modification using only dithionite as
      an electron donor. Combining ferredoxin fusion and surface charge modification
      showed progressively improved activity in an in vitro assay with purified enzyme.

PMID- 25603179
TI  - Medullary thymic epithelial cells and central tolerance in autoimmune hepatitis
      development: novel perspective from a new mouse model.
AB  - Autoimmune hepatitis (AIH) is an immune-mediated disorder that affects the liver
      parenchyma. Diagnosis usually occurs at the later stages of the disease,
      complicating efforts towards understanding the causes of disease development.
      While animal models are useful for studying the etiology of autoimmune disorders,
      most of the existing animal models of AIH do not recapitulate the chronic course
      of the human condition. In addition, approaches to mimic AIH-associated liver
      inflammation have instead led to liver tolerance, consistent with the high
      tolerogenic capacity of the liver. Recently, we described a new mouse model that
      exhibited spontaneous and chronic liver inflammation that recapitulated the known
      histopathological and immunological parameters of AIH. The approach involved
      liver-extrinsic genetic engineering that interfered with the induction of T-cell
      tolerance in the thymus, the very process thought to inhibit AIH induction by
      liver-specific expression of exogenous antigens. The mutation led to depletion of
      specialized thymic epithelial cells that present self-antigens and eliminate
      autoreactive T-cells before they exit the thymus. Based on our findings, which
      are summarized below, we believe that this mouse model represents a relevant
      experimental tool towards elucidating the cellular and molecular aspects of AIH
      development and developing novel therapeutic strategies for treating this
      disease. 

PMID- 25603183
TI  - [Clobetasol unnecessarily narrows the foreskin].

PMID- 25603182
TI  - Efficient synthesis of a maghemite/gold hybrid nanoparticle system as a magnetic
      carrier for the transport of platinum-based metallotherapeutics.
AB  - The preparation and thorough characterization of a hybrid magnetic carrier system
      for the possible transport of activated platinum-based anticancer drugs, as
      demonstrated for cisplatin (cis-[Pt(NH3)2Cl2], CDDP), are described. The final
      functionalized mag/Au-LA-CDDP* system consists of maghemite/gold nanoparticles
      (mag/Au) coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic
      acid) and functionalized by activated cisplatin in the form of cis
      [Pt(NH3)2(H2O)2]2+ (CDDP*). The relevant techniques (XPS, EDS, ICP-MS) proved the
      incorporation of the platinum-containing species on the surface of the studied
      hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical
      with an average size of 12 nm, while their superparamagnetic feature was proven
      by 57Fe Mossbauer spectroscopy. In the case of mag/Au, mag/Au-HLA and mag/Au-LA
      CDDP*, weaker magnetic interactions among the Fe3+ centers of maghemite, as
      compared to maghemite nanoparticles (mag), were detected, which can be associated
      with the non-covalent coating of the maghemite surface by gold. The pH and time
      dependent stability of the mag/Au-LA-CDDP* system in different media, represented
      by acetate (pH 5.0), phosphate (pH 7.0) and carbonate (pH 9.0) buffers and
      connected with the release of the platinum-containing species, showed the ability
      of CDDP* to be released from the functionalized nanosystem. 

PMID- 25603184
TI  - [When Sweden's point was health care--Swedish medical efforts in the Finnish
      Winter War in 1939-1940].
AB  - More than 400 Swedish volunteers participated in medical units in the Finnish
      Winter War 1939-40. The Swedish sympathies for Finland were strong and the
      medical contribution was seen both as a humanitarian and a military action. The
      Swedish red cross was one of the participating organizations but the red crosses
      where removed from the vehicles. Much of the medical equipment came from the
      Swedish army. The link to the Swedish voluntary corps was very strong and many of
      the treated patients were Swedes. The contribution met with great acclaim while
      it lasted. Afterwards, however, only a third of the doctors declared their
      participation. Perhaps they wanted to avoid being associated with the war.

PMID- 25603186
TI  - [Studies of antidotes for NOAK show good results].

PMID- 25603187
TI  - [Female doctors' association: the right to abortion must be defended].

PMID- 25603188
TI  - Effect of protein incorporation on the nanostructure of the bicontinuous
      microemulsion phase of Winsor-III systems: a small-angle neutron scattering
      study.
AB  - Small-angle neutron scattering (SANS) analysis using the Teubner-Strey model has
      been employed to evaluate the effect of protein incorporation into the middle,
      bicontinuous microemulsion (BMUE) phase of Winsor-III (WIII) systems formed by an
      aerosol-OT (AOT)/alkyl ethoxylate mixed surfactant system to understand better
      the extraction of proteins into and out of BMUEs and to study the effect of
      proteins on a system that serves as a biomimetic analog of cell membranes. Under
      conditions of high salinity, the incorporation of positively charged proteins
      cytochrome c, lysozyme, and alpha-chymotrypsin, near their solubilization limit
      in the BMUEs promoted the release of water and oil from the BMUEs, a decrease in
      the quasi-periodic repeat distance (d), an increase in ordering (a decrease in
      the amphiphilicity factor, fa) for the surfactant monolayers, and a decrease in
      the surface area per surfactant headgroup, suggesting that the proteins affected
      the self-assembly of components in the BMUE phase and produced Debye shielding of
      AOT's sulfonate headgroup. For WIII systems possessing lower salinity, cytochrome
      c reduced the efficiency of surfactant in the BMUE phase, noted by increases in d
      and fa, suggesting that the enzyme and AOT underwent ion pairing. The results of
      this study demonstrate the importance of ionic strength to modulate protein
      surfactant interactions, which in turn will control the release of proteins
      encapsulated in the BMUEs, relevant to WIII-based protein extraction and
      controlled release from BMUE delivery systems, and demonstrate the utility of
      BMUEs as a model system to understand the effect of proteins on biomembranes. 

PMID- 25603189
TI  - Estimating Contact Exposure in Football Using the Head Impact Exposure Estimate.
AB  - Over the past decade, there has been significant debate regarding the effect of
      cumulative subconcussive head impacts on short and long-term neurological
      impairment. This debate remains unresolved, because valid epidemiological
      estimates of athletes' total contact exposure are lacking. We present a measure
      to estimate the total hours of contact exposure in football over the majority of
      an athlete's lifespan. Through a structured oral interview, former football
      players provided information related to primary position played and participation
      in games and practice contacts during the pre-season, regular season, and post
      season of each year of their high school, college, and professional football
      careers. Spring football for college was also included. We calculated contact
      exposure estimates for 64 former football players (n = 32 college football only,
      n = 32 professional and college football). The head impact exposure estimate
      (HIEE) discriminated between individuals who stopped after college football, and
      individuals who played professional football (p < 0.001). The HIEE measure was
      independent of concussion history (p = 0.82). Estimating total hours of contact
      exposure may allow for the detection of differences between individuals with
      variation in subconcussive impacts, regardless of concussion history. This
      measure is valuable for the surveillance of subconcussive impacts and their
      associated potential negative effects.

PMID- 25603190
TI  - Antimicrobial Packaging for Extending the Shelf Life of Bread-A Review.
AB  - Antimicrobial packaging is an important form of active packaging that can release
      antimicrobial substances for enhancing the quality and safety of food during
      extended storage. It is in response to consumers demand for preservative-free
      food as well as more natural, disposable, biodegradable, and recyclable food
      packaging materials. The potential of a combination of allyl isothiocyanate and
      potassium sorbate incorporated into polymers in providing the needed natural
      antimicrobial protection for bread products is discussed. The role of double
      extrusion process as a means for obtaining a homogeneous mix of the sorbate into
      the polymer (polyethylene or ethylenevinyalcohol), is highlighted. 

PMID- 25603194
TI  - Unveiling nanometer scale extinction and scattering phenomena through combined
      electron energy loss spectroscopy and cathodoluminescence measurements.
AB  - Plasmon modes of the exact same individual gold nanoprisms are investigated
      through combined nanometer-resolved electron energy-loss spectroscopy (EELS) and
      cathodoluminescence (CL) measurements. We show that CL only probes the radiative
      modes, in contrast to EELS, which additionally reveals dark modes. The
      combination of both techniques on the same particles thus provides complementary
      information and also demonstrates that although the radiative modes give rise to
      very similar spatial distributions when probed by EELS or CL, their resonant
      energies appear to be different. We trace this phenomenon back to plasmon
      dissipation, which affects in different ways the plasmon signatures probed by
      these techniques. Our experiments are in agreement with electromagnetic numerical
      simulations and can be further interpreted within the framework of a quasistatic
      analytical model. We therefore demonstrate that CL and EELS are closely related
      to optical scattering and extinction, respectively, with the addition of
      nanometer spatial resolution. 

PMID- 25603192
TI  - An assessment of intra-patient variability on observed relationships between wall
      shear stress and plaque progression in coronary arteries.
AB  - BACKGROUND: Wall shear stress (WSS) has been associated with sites of plaque
      localization and with changes in plaque composition in human coronary arteries.
      Different values have been suggested for categorizing WSS as low, physiologic or
      high; however, uncertainties in flow rates, both across subjects and within a
      given individual, can affect the classification of WSS and thus influence the
      observed relationships between local hemodynamics and plaque changes over time.
      This study examines the effects of uncertainties in flow rate boundary conditions
      upon WSS values and investigates the influence of this variability on the
      observed associations of WSS with changes in VH-IVUS derived plaque components.
      METHODS: Three patients with coronary artery disease underwent baseline and 12
      month follow-up angiography and virtual histology-intravascular ultrasound (VH
      IVUS) measurements. Coronary artery models were reconstructed from the data and
      models with and without side-branches were created. Patient-specific Doppler
      ultrasound (DUS) data were employed as inflow boundary conditions and
      computational fluid dynamics was used to calculate the WSS in each model.
      Further, the influence of representative coronary artery flow waveforms upon WSS
      values was investigated and the concept of treating WSS using relative, rather
      than actual, values was explored. RESULTS: Models that included side-branch
      outflows and subject-specific DUS velocities were considered to be the reference
      cases. Hemodynamic differences were caused by the exclusion of side-branches and
      by imposing alternative velocity waveforms. One patient with fewer side-branches
      and a scaled generic waveform had little deviation from the reference case, while
      another patient with several side-branches excluded showed much larger departures
      from the reference situation. Differences between models and the respective
      reference cases were reduced when data were analyzed using relative, rather than
      actual, WSS. CONCLUSIONS: When considering individual subjects, large variations
      in patient-specific flow rates and exclusion of multiple side-branches in
      computational models can cause significant differences in observed associations
      between plaque evolution and ranges of computed WSS. These differences may
      contribute to the large variability typically found among subjects in pooled
      populations. Relative WSS may be more useful than actual WSS as a correlative
      variable when there is a large degree of uncertainty in flow rate data.

PMID- 25603195
TI  - All Behcet's cases with intracardiac thrombus should be evaluated for pulmonary
      and vascular involvement.

PMID- 25603197
TI  - Characterisation of human saliva as a platform for oral dissolution medium
      development.
AB  - Human saliva is a biological fluid of great importance in the field of
      dissolution testing. However, until now, no consensus has been reached on its key
      characteristics relevant to dissolution testing. As a result, it is difficult to
      select or develop an in vitro dissolution medium to best represent human saliva.
      In this study, the pH, buffer capacity, surface tension, viscosity and flow rate
      of both unstimulated (US) and stimulated (SS) human saliva were investigated in
      order to provide a platform of reference for future dissolution studies using
      simulated salivary fluids. Age and gender related differences in a sample size of
      30 participants for each parameter were investigated. Significant differences
      were established between US and SS for all characteristics except surface
      tension. Therefore, the requirement for using two simulated salivary fluids
      should be considered when developing an oral dissolution model. 

PMID- 25603198
TI  - Intravitreal clearance and volume of distribution of compounds in rabbits: In
      silico prediction and pharmacokinetic simulations for drug development.
AB  - The aims of this research were to (1) create a curated universal database of
      intravitreal volumes of distribution (Vss, ivt) and clearances (CL ivt) of small
      molecular weight compounds and macromolecules and (2) to develop quantitative
      structure property relationship (QSPR) and pharmacokinetic models for the
      estimation of vitreal drug concentrations based on the compound structure. Vss,
      ivt and CL ivt values were determined from the available literature on
      intravitreal drug administration using compartmental models and curve fitting. A
      simple QSPR model for CL ivt of small molecular weight compounds was obtained
      with two descriptors: Log D7.4 and hydrogen bond donor capacity. The model
      predicted the internal and external test sets reliably with a mean fold error of
      1.50 and 1.33, respectively (Q(2)Y=0.62). For 80% of the compounds the Vss, ivt
      was 1.18-2.28 ml; too narrow range for QSPR model building. Integration of the
      estimated Vss, ivt and predicted CL ivt parameters into pharmacokinetic
      simulation models allows prediction of vitreous drug concentrations after
      intravitreal administration. The present work presents for the first time a
      database of CL ivt and Vss, ivt values and the dependence of the CL ivt values on
      the molecular structure. The study provides also useful in silico tools to
      investigate a priori the intravitreal pharmacokinetic profiles for intravitreally
      injected candidate compounds and drug delivery systems.

PMID- 25603196
TI  - The role of reactive oxygen species in mesenchymal stem cell adipogenic and
      osteogenic differentiation: a review.
AB  - Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering
      and regenerative medicine. The multipotent stem cell component of MSC isolates is
      able to differentiate into derivatives of the mesodermal lineage including
      adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have
      been described in the regulation of adipogenesis and osteogenesis. However,
      stimulation of osteogenesis appears to suppress adipogenesis and vice-versa.
      Increasing evidence implicates a tight regulation of these processes by reactive
      oxygen species (ROS). ROS are short-lived oxygen-containing molecules that
      display high chemical reactivity toward DNA, RNA, proteins, and lipids.
      Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major
      sources of ROS production during MSC differentiation. ROS are thought to interact
      with several pathways that affect the transcription machinery required for MSC
      differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the
      other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest
      of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are
      therefore critical for MSC terminal differentiation, although the precise
      sources, localization, levels and the exact species of ROS implicated remain to
      be determined. This review provides a detailed overview of the influence of ROS
      on adipogenic and osteogenic differentiation in MSCs. 

PMID- 25603199
TI  - Mucus permeating thiomer nanoparticles.
AB  - The aim of this study was to develop and evaluate a novel mucoadhesive drug
      delivery system based on thiolated poly(acrylic acid) nanoparticles exhibiting
      mucolytic properties to enhance particle diffusion into deeper mucus regions
      before adhesion. Mediated by a carbodiimide, cysteine and the mucolytic enzyme
      papain were covalently attached to poly(acrylic acid) via amide bond formation.
      The conjugates were co-precipitated with calcium chloride in order to obtain
      papain modified (PAA-pap) and thiolated nanoparticles (PAA-cys) as well as
      particles containing both conjugates (PAA-cys-pap). The nanoparticulate systems
      were characterized regarding particle size distribution and zeta potential.
      Particle transport was investigated by diffusion studies across intestinal mucus
      using two different techniques. Furthermore, mucoadhesive properties of all
      particles were evaluated via rheological measurements. Results demonstrated that
      all nanoparticles were in a size range of 158-214 nm and showed negative zeta
      potentials. Due to the presence of papain, the PAA-cys-pap particles were capable
      of cleaving mucoglycoprotein substructures and consequently exhibited a 2.0-fold
      higher penetration into the mucus layer in comparison with PAA-cys particles.
      Within the rheological studies, an 1.9-fold increase in mucoadhesion could be
      achieved for the nanoparticulate system based on thiolated PAA compared to papain
      modified particles (PAA-pap). Therefore, the newly developed particulate system
      (PAA-cys-pap) is characterized by mucoadhesive as well as mucolytic properties.
      The combination of both effects - mucus-permeating and mucoadhesive properties -
      might be a promising strategy for the development of oral drug delivery systems
      to overcome the mucus barrier and providing a prolonged residence time close to
      the absorption membrane.

PMID- 25603200
TI  - Perioperative temperature management: time for a new standard of care?

PMID- 25603201
TI  - Tilting at aortocaval compression.

PMID- 25603202
TI  - Intraoperative core temperature patterns, transfusion requirement, and hospital
      duration in patients warmed with forced air.
AB  - BACKGROUND: Core temperature patterns in patients warmed with forced air remain
      poorly characterized. Also unknown is the extent to which transient and mild
      intraoperative hypothermia contributes to adverse outcomes in broad populations.
      METHODS: We evaluated esophageal (core) temperatures in 58,814 adults having
      surgery lasting >60 min who were warmed with forced air. Independent associations
      between hypothermic exposure and transfusion requirement and duration of
      hospitalization were evaluated. RESULTS: In every percentile subgroup, core
      temperature decreased during the first hour and subsequently increased. The mean
      lowest core temperature during the first hour was 35.7 +/- 0.6 degrees C. Sixty
      four percent of the patients reached a core temperature threshold of <36 degrees
      C 45 min after induction; 29% reached a core temperature threshold of <35.5
      degrees C. Nearly half the patients had continuous core temperatures <36 degrees
      C for more than an hour, and 20% of the patients were <35.5 degrees C for more
      than an hour. Twenty percent of patients had continuous core temperatures <36
      degrees C for more than 2 h, and 8% of the patients were below 35.5 degrees C for
      more than 2 h. Hypothermia was independently associated with both transfusions
      and duration of hospitalization, although the prolongation of hospitalization was
      small. CONCLUSIONS: Even in actively warmed patients, hypothermia is routine
      during the first hour of anesthesia. Thereafter, average core temperatures
      progressively increase. Nonetheless, intraoperative hypothermia was common, and
      often prolonged. Hypothermia was associated with increased transfusion
      requirement, which is consistent with numerous randomized trials.

PMID- 25603203
TI  - Effect of lateral tilt angle on the volume of the abdominal aorta and inferior
      vena cava in pregnant and nonpregnant women determined by magnetic resonance
      imaging.
AB  - BACKGROUND: Left-lateral tilt position is used to reduce assumed aortocaval
      compression by the pregnant uterus. METHODS: Magnetic resonance images of 10
      singleton parturients at full term and 10 healthy nonpregnant women were obtained
      for measurement of the abdominal aorta and inferior vena cava volume between the
      L1-L2 disk and L3-L4 disk levels in both the supine and left-lateral tilt
      positions (15 degrees , 30 degrees , and 45 degrees ) maintained by insertion of
      a 1.5-m-long polyethylene foam placed under the right side of the parturient's
      body. RESULTS: Aortic volume did not differ significantly between parturients and
      nonpregnant women in the supine position (12.7 +/- 2.0 vs.12.6 +/- 2.1 ml, mean
      +/- SD; mean difference, -0.1; 95% confidence interval [CI], -2.0 to 1.9; P =
      0.95). Inferior vena cava volume in the supine position was significantly lower
      in parturients than in nonpregnant women (3.2 +/- 3.4 vs.17.5 +/- 7.8 ml; mean
      difference, 14.3; 95% CI, 8.3-20.2; P < 0.001). Aortic volume in parturients did
      not differ among left-lateral tilt positions. Inferior vena cava volume in the
      parturients was not increased at 15 degrees  (3.0 +/- 2.1 ml; mean difference, 
      0.2; 95% CI, -1.5 to 1.2; P > 0.99), but was significantly increased at 30
      degrees  (11.5 +/- 8.6 ml; mean difference, 8.3; 95% CI, 2.3-14.2; P = 0.009) and
      45 degrees  (10.9 +/- 6.8 ml; mean difference, 7.7; 95% CI, 2.2-13.1; P = 0.015).
      CONCLUSIONS: In parturients, the aorta was not compressed, and a 15 degrees  left
      lateral tilt position did not effectively reduce inferior vena cava compression.

PMID- 25603204
TI  - From Paris to Tunis: bellon advertising xylocaine.

PMID- 25603206
TI  - SPAR(klet) WARS: Erie's Duncan et al. vs. Cleveland's Hingson et al.

PMID- 25603207
TI  - A Floridian Salute to a Clevelander: Liberty Ship SS Harvey Cushing.

PMID- 25603205
TI  - Discovery of a novel general anesthetic chemotype using high-throughput
      screening.
AB  - BACKGROUND: The development of novel anesthetics has historically been a process
      of combined serendipity and empiricism, with most recent new anesthetics
      developed via modification of existing anesthetic structures. METHODS: Using a
      novel high-throughput screen employing the fluorescent anesthetic 1
      aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein
      target(s), we screened a 350,000 compound library for competition with 1
      aminoanthracene-apoferritin binding. Hit compounds meeting structural criteria
      had their binding affinities for apoferritin quantified with isothermal titration
      calorimetry and were tested for gamma-aminobutyric acid type A receptor binding
      using a flunitrazepam binding assay. Chemotypes with a strong presence in the top
      700 and exhibiting activity via isothermal titration calorimetry were selected
      for medicinal chemistry optimization including testing for anesthetic potency and
      toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity
      and high potency were tested for anesthetic potency in mice. RESULTS: From an
      initial chemical library of more than 350,000 compounds, we identified 2,600
      compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A
      subset of compounds chosen by structural criteria (700) was successfully
      reconfirmed using the initial assay. Based on a strong presence in both the
      initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was
      assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts
      identified four compounds with high potency and low toxicity in tadpoles, two
      were found to be effective novel anesthetics in mice. CONCLUSION: The authors
      demonstrate the first use of a high-throughput screen to successfully identify a
      novel anesthetic chemotype and show mammalian anesthetic activity for members of
      that chemotype.

PMID- 25603208
TI  - Management of difficult airways: which is the safest approach after reviewing
      virtual laryngo-tracheo-bronchoscopy imaging?

PMID- 25603209
TI  - In reply.

PMID- 25603210
TI  - Duration of hypotension (still) matters.

PMID- 25603211
TI  - In reply.

PMID- 25603212
TI  - Aspiration during monitored anesthesia care.

PMID- 25603213
TI  - In reply.

PMID- 25603214
TI  - Role of recruitment maneuvers for lung-protective ventilation in the operating
      room remains unclear.

PMID- 25603215
TI  - In reply.

PMID- 25603223
TI  - MR1 presentation of vitamin B-based metabolite ligands.
AB  - The major histocompatibility complex class I-related molecule MR1 can bind a
      novel class of antigens, namely a family of related small organic vitamin B
      metabolites. When bound to MR1 these metabolites are presented to a population of
      innate-like T cells, mucosal-associated invariant T (MAIT) cells that express a
      semi-invariant T cell receptor (TCR). Several non-activating and activating MR1
      restricted ligands have been described, which are the degradation products of, or
      intermediates of, vitamin B9 (folic acid) or vitamin B2 (riboflavin),
      respectively. The MAIT-activating intermediates of the riboflavin synthesis
      pathway are unique to a wide range of microbes, and accordingly represent a
      molecular signature of microbial infection. Recently insights into the binding of
      these vitamin B metabolites to MR1, and subsequent recognition by the MAIT TCR,
      have been gleaned, illustrating a novel antigen presentation system. 

PMID- 25603224
TI  - Differences in pain subtypes between Hispanic and non-Hispanic white women with
      chronic vulvar pain.
AB  - OBJECTIVES: Compared with non-Hispanic Whites, Hispanic women have significantly
      higher prevalence of chronic vulvar pain (CVP), which is known to have
      heterogeneous subtypes. However, it is not known whether subtypes differ by
      ethnicity, and improved understanding of subtypes may allow for targeted clinical
      assessment and therapies. We examined subtypes to determine whether they differed
      by ethnicity. METHODS: Data were from 1,551 women who reported chronic vulvar
      pain consistent with vulvodynia in a population-based, cross-sectional study of
      women from the Minneapolis/St. Paul metropolitan area, during the years 2010
      2013, who returned a validated screener survey about vulvar pain. RESULTS: Among
      women with CVP, Hispanics reported more primary vulvodynia (adjusted [adj.] risk
      ratio=1.47; p<0.01), defined as pain with first intercourse or tampon use, and
      tended to be more likely to describe a burning pain (adj. risk ratio=1.45;
      p=0.06). Hispanic women with CVP were 17% more likely than non-Hispanic Whites
      with CVP to have their pain alleviated with some type of behavior/remedy
      (p=0.01); for example, among the subgroup of women with CVP who used yeast cream,
      Hispanics more often reported benefit to their pain (adj. risk ratio=1.51;
      p<0.01). DISCUSSION: We examined women with CVP and found that in comparison to
      their non-Hispanic White counterparts, Hispanic women are more likely to report a
      burning sensation and more likely to have primary vulvodynia, a subtype that is
      associated with great burden on the lives of affected women.

PMID- 25603225
TI  - Facile fabrication of robust silk nanofibril films via direct dissolution of silk
      in CaCl2-formic acid solution.
AB  - In this study, we report for the first time a novel silk fibroin (SF) nanofibrous
      films with robust mechanical properties that was fabricated by directly
      dissolving silk in CaCl2-formic acid solution. CaCl2-FA dissolved silk rapidly at
      room temperature, and more importantly, it disintegrated silk into nanofibrils
      instead of separate molecules. The morphology of nanofibrils crucially depended
      on CaCl2 concentrations, which resulted in different aggregation nanostructure in
      SF films. The SF film after drawing had maximum elastic modulus, ultimate tensile
      strength, and strain at break reaching 4 GPa, 106 MPa, and 29%, respectively, in
      dry state and 206 MPa, 28 MPa, and 188%, respectively, in wet state. Moreover,
      multiple yielding phenomena and substantially strain-hardening behavior was also
      observed in the stretched films, indicating the important role played by
      preparation method in regulating the mechanical properties of SF films. These
      exceptional and unique mechanical properties were suggested to be caused by
      preserving silk nanofibril during dissolution and stretching to align these
      nanofibrils. Furthermore, the SF films exhibit excellent biocompatibility,
      supporting marrow stromal cells adhesion and proliferation. The film preparation
      was facile, and the resulting SF films manifested enhanced mechanical properties,
      unique nanofibrous structures, and good biocompability. 

PMID- 25603226
TI  - Gastrointestinal dysfunction relating to the provision of nutrition in the
      critically ill.
AB  - PURPOSE OF REVIEW: During critical illness, enteral nutrition remains central to
      clinical care and an understanding of gut dysfunction is therefore important.
      Contemporary data have contributed to our knowledge in this area and this review
      will concentrate on recently published studies. RECENT FINDINGS: It is difficult
      to precisely measure gastric emptying and nutrient absorption as part of routine
      clinical care. However, techniques for the measurement of these parameters for
      research purposes have been refined, studied and validated. These methodologies
      allow the evaluation of novel treatments that modulate gastric emptying.
      Quantification and an understanding of the mechanisms of nutrient malabsorption
      may facilitate the development of therapeutic agents to improve absorption and/or
      formulae, which are more readily absorbed, thereby improving nutritional and
      clinical outcomes. SUMMARY: Improved understanding of gut pathophysiology in
      critical illness provides opportunities for the development and testing of novel
      and targeted treatment strategies, with the objective to improve clinical
      outcomes in this group.

PMID- 25603227
TI  - Muscle weakness and nutrition therapy in ICU.
AB  - PURPOSE OF REVIEW: Muscle wasting is common in severe critical illness. ICU
      acquired weakness (ICU-AW) contributes to acute and long-term morbidity and
      mortality. The question remains whether nutrition therapy in ICU can prevent or
      attenuate these complications. This review aims at integrating the most recent
      clinical data in order to answer this important clinical and research question.
      Clinical evidence was obtained from randomized controlled trials (RCTs). Results
      from animal experiments and observational studies are referred to when -
      respectively - providing possible explanatory mechanisms or new hypotheses.
      RECENT FINDINGS: Although muscle wasting has been reproducibly quantified early
      in ICU, its relationship with ICU-AW has not yet been convincingly established.
      All recent RCTs evaluating increased energy/protein intake during ICU week 1
      failed to demonstrate a protective effect against ICU-AW or physical function
      limitations. In one RCT, early parenteral nutrition increased the incidence of
      ICU-AW. The latter finding might be explained by suppressed autophagy. SUMMARY:
      Current evidence does not support improved physical function with increased
      energy/protein provision in the first ICU week. Future RCTs aimed at reducing the
      burden of ICU-AW and improving long-term function should particularly focus on
      nutrition beyond the acute phase of critical illness and on non-nutritional
      interventions such as early mobilization.

PMID- 25603228
TI  - Defect-induced photoluminescence in monolayer semiconducting transition metal
      dichalcogenides.
AB  - It is well established that defects strongly influence properties in two
      dimensional materials. For graphene, atomic defects activate the Raman-active
      centrosymmetric A1g ring-breathing mode known as the D-peak. The relative
      intensity of this D-peak compared to the G-band peak is the most widely accepted
      measure of the quality of graphene films. However, no such metric exists for
      monolayer semiconducting transition metal dichalcogenides such as WS2 or MoS2.
      Here we intentionally create atomic-scale defects in the hexagonal lattice of
      pristine WS2 and MoS2 monolayers using plasma treatments and study the evolution
      of their Raman and photoluminescence spectra. High-resolution transmission
      electron microscopy confirms plasma-induced creation of atomic-scale point
      defects in the monolayer sheets. We find that while the Raman spectra of
      semiconducting transition metal dichalcogenides (at 532 nm excitation) are
      insensitive to defects, their photoluminescence reveals a distinct defect-related
      spectral feature located ~0.1 eV below the neutral free A-exciton peak. This peak
      originates from defect-bound neutral excitons and intensifies as the two
      dimensional (2D) sheet is made more defective. This spectral feature is
      observable in air under ambient conditions (room temperature and atmospheric
      pressure), which allows for a relatively simple way to determine the
      defectiveness of 2D semiconducting nanosheets. Controlled defect creation could
      also enable tailoring of the optical properties of these materials in
      optoelectronic device applications. 

PMID- 25603229
TI  - Comparison of laser in situ keratomileusis flaps created by 2 femtosecond lasers.
AB  - PURPOSE: To compare flap morphology created by the WaveLight FS200 femtosecond
      laser and the VisuMax femtosecond laser, assessing the uniformity, accuracy, and
      predictability of flap creation. METHODS: A total of 400 eyes had corneal flaps
      created with the WaveLight FS200 femtosecond laser (200 eyes) or the VisuMax
      femtosecond laser (200 eyes). The desired flap thickness was 110 MUm. At 1 week
      postoperatively, all eyes were evaluated with RTVue Fourier-domain optical
      coherence tomography. Dimensions of the flaps were tested for their regularity,
      uniformity, accuracy, and predictability comparison. RESULTS: One week after
      surgery, the central flap thickness and the mean flap thickness of the FS200
      group were 105.4 +/- 3.4 MUm and 105.7 +/- 2.6 MUm, respectively. They were both
      thinner than those of the VisuMax group, which were 110.8 +/- 3.9 MUm and 111.3
      +/- 2.3 MUm, respectively. The mean deviation between the achieved and attempted
      flap thickness of the FS200 group (5.2 +/- 1.9 MUm) was greater than that of the
      VisuMax group (3.2 +/- 1.8 MUm). Flap thickness measurements at 36 points in both
      groups were close to the intended thickness. Morphology of the flaps in the 0-,
      45-, 90-, and 135-degree lines created by the FS200 femtosecond laser and VisuMax
      femtosecond laser were uniform and regular. CONCLUSIONS: Flap dimensions created
      by the WaveLight FS200 femtosecond laser and VisuMax femtosecond laser were
      uniform and regular. Although the flap thickness created by the FS200 was less
      than that created by the VisuMax, measurements of both femtosecond lasers were
      close to the intended thickness.

PMID- 25603230
TI  - Onset of ocular graft-versus-host disease symptoms after allogeneic hematopoietic
      stem cell transplantation.
AB  - OBJECTIVE: To study the factors affecting the time to onset of ocular graft
      versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). METHODS: A retrospective chart review of 200
      patients with ocular GVHD was performed to evaluate the association between
      various donor-recipient characteristics and the time to onset of ocular GVHD
      after allo-HSCT. RESULTS: The median time to onset of chronic ocular GVHD after
      allo-HSCT was 293 days (range, 26-2308 days). Patients receiving fully human
      leukocyte antigen (HLA)-matched transplants had a delayed onset of ocular GVHD
      (median, 294 days) compared with mismatched transplants (219 days; P = 0.029).
      HLA-matched transplants from related donors had delayed onset of ocular GVHD (307
      days) compared with HLA-matched (286 days; P = 0.168) and HLA-mismatched (231
      days; P = 0.015) transplants from unrelated donors. Ocular GVHD followed systemic
      GVHD in 76% of patients but preceded systemic disease in 7%, occurred
      concurrently in 15%, and was not associated with systemic GVHD in 2% of patients.
      The time elapsed between the occurrence of systemic and ocular GVHD was
      significantly longer in matched-related transplants (250 days) than in matched
      unrelated transplants (120 days; P = 0.004). CONCLUSIONS: The onset of ocular
      GVHD after allo-HSCT is variable and is influenced by donor-recipient matching
      characteristics. In the majority of patients with GVHD, ocular involvement
      follows the occurrence of systemic manifestations; however, importantly, it can
      also precede or develop independently of systemic disease in a minority of
      patients. Regular ophthalmic follow-up is recommended after allo-HSCT regardless
      of concurrent systemic GVHD status.

PMID- 25603231
TI  - Seasonal, geographic, and antimicrobial resistance patterns in microbial
      keratitis: 4-year experience in eastern Pennsylvania.
AB  - PURPOSE: The aim of this study was to review the demographics, causative
      organisms, seasonal and geographic variation, and antimicrobial resistance
      patterns of microbial keratitis at our institution over a 4-year period. METHODS:
      Electronic medical records of all patients with microbial keratitis who underwent
      corneal culturing at a single institution in eastern Pennsylvania between January
      1, 2009 and December 31, 2012 were reviewed. RESULTS: A total of 311 patients
      representing 323 instances of infectious keratitis were analyzed. The most
      frequently implicated organisms in contact lens-related infections were
      Pseudomonas aeruginosa for bacteria and Fusarium species for fungus, compared
      with Staphylococcus aureus and Candida species in non-contact lens-associated
      bacterial infections. Bacterial keratitis occurred most frequently in spring and
      least frequently in winter (P = 0.024). Patients who live in large fringe metro
      (suburban) areas accounted for the highest proportion of infectious keratitis
      cases. P. aeruginosa and methicillin-sensitive S. aureus isolates were highly
      susceptible to fluoroquinolones, whereas 32% of coagulase-negative staphylococcus
      isolates tested were resistant to moxifloxacin and gatifloxacin, and all
      methicillin-resistant S. aureus organisms tested were resistant to these 2
      fluoroquinolones. No organisms tested were resistant to tobramycin, gentamicin,
      or vancomycin. No fungal infections tested were resistant to voriconazole.
      CONCLUSIONS: Most infectious keratitis occurred in nonwinter months and in
      patients from suburban counties. Although fluoroquinolones were effective against
      the most common bacteria, staphylococcal species exhibited a high rate of
      resistance, representing a therapeutic challenge given the increasing use of
      fluoroquinolones as first-line monotherapy. No organisms tested were resistant to
      tobramycin, gentamicin, vancomycin, or voriconazole.

PMID- 25603232
TI  - In vivo confocal microscopy of pine processionary caterpillar hair-induced
      keratitis.
AB  - PURPOSE: Multimodal imaging of processionary caterpillar hair-induced keratitis
      with anterior segment optical coherence tomography and in vivo confocal
      microscopy. METHODS: Case report. RESULTS: A 25-year-old woman presented with
      acute keratitis induced by multiple tiny processionary caterpillar hairs. She
      initially experienced severe pain and moderate vision loss, which gradually
      improved within a few weeks. Diagnosis was confirmed by in vivo confocal
      microscopy showing a pathognomonic image strictly comparable with ex vivo
      microscopy photography. CONCLUSIONS: To the best of our knowledge, this is the
      first case of corneal in vivo confocal imaging of a caterpillar hair with
      confirmation by ex vivo microscopy.

PMID- 25603233
TI  - Association of IL-21 cytokine with severity of primary Sjogren syndrome dry eye.
AB  - PURPOSE: IL-21 plays an important role in primary Sjogren syndrome (SS)
      pathogenesis. The purpose of this study was to evaluate IL-21 expression in tears
      and the conjunctiva and to analyze the impact of IL-21 on primary SS dry eyes.
      METHODS: Eighty subjects were enrolled in this study: 30 patients with primary SS
      dry eye (30 eyes); 30 patients with non-SS dry eye (30 eyes), and 20 normal
      controls. Tear IL-21 levels were measured by flow cytometry, and IL-21 gene
      expression in the conjunctiva from impression cytology was evaluated by
      quantitative polymerase chain reaction. Ocular Surface Disease Index, tear film
      breakup time, Schirmer I test, and ocular surface staining scores were obtained
      for all patients. RESULTS: Primary SS dry eyes had significantly higher tear IL
      21 levels than non-SS dry eyes and normal controls (P < 0.01). In addition, IL-21
      gene expression in the conjunctiva was also higher in primary SS dry eyes than in
      non-SS dry eyes and normal controls (P < 0.01). However, there were no
      significant differences in IL-21 expression in tears and the conjunctiva between
      non-SS dry eyes and controls. The tear IL-21 level was significantly correlated
      with ocular surface stain scores (r = 0.54, P < 0.01) and Schirmer I test values
      (r = -0.23, P < 0.05) in primary SS dry eyes. CONCLUSIONS: Our findings suggest
      that severity of primary SS dry eye is associated with IL-21.

PMID- 25603234
TI  - Capsaicin protects endothelial cells and macrophage against oxidized low-density
      lipoprotein-induced injury by direct antioxidant action.
AB  - Atherosclerosis is a chronic inflammatory vascular disease. It is characterized
      by endothelial dysfunction, lipid accumulation, leukocyte activation, and the
      production of inflammatory mediators and reactive oxygen species (ROS).
      Capsaicin, a biologically active compound of the red pepper and chili pepper, has
      several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic
      biological effects. However, its protective effects on foam cell formation and
      endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain
      unclear. In this study, we evaluated the anti-oxidative activity of capsaicin,
      and determined the mechanism by which capsaicin rescues human umbilical vein
      endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative
      activity of capsaicin was defined by Apo B fragmentation and conjugated diene
      production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS
      generation, as well as subsequent mitochondrial membrane potential collapse,
      cytochrome c expression, chromosome condensation, and caspase-3 activation
      induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in
      macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL
      induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation. 

PMID- 25603235
TI  - Identification of new inhibitors for human hematopoietic prostaglandin D2
      synthase among FDA-approved drugs and other compounds.
AB  - OBJECTIVE: Hematopoietic prostaglandin D2 synthase (HPGDS) is a member of the
      Sigma class glutathione transferases (GSTs) catalyzing the isomerization of
      prostaglandin H2 to prostaglandin D2, a mediator of allergy and inflammation
      responses. Selective inhibitors of human HPGDS are expected to be of therapeutic
      importance in relieving symptoms related to allergy and asthma. Hence, a
      collection of diverse FDA-approved compounds was screened for potential novel
      applications as inhibitors of HPGDS. METHODS: The catalytic activity of purified
      HPGDS was used for inhibition studies in vitro. RESULTS: Our inhibition studies
      revealed 23 compounds as effective inhibitors of HPGDS with IC50 values in the
      low micromolar range. Erythrosine sodium, suramin, tannic acid and sanguinarine
      sulfate were characterized with IC50 values of 0.2, 0.3, 0.4, and 0.6 MUM,
      respectively. Kinetic inhibition analysis showed that erythrosine sodium is a
      nonlinear competitive inhibitor of HPGDS, while suramin, tannic acid and
      sanguinarine sulfate are linear competitive inhibitors. CONCLUSION: The results
      show that certain FDA-approved compounds may have pharmacological effects not
      previously realized that warrant further consideration in their clinical use.

PMID- 25603237
TI  - Characteristics of atmospheric visibility and its relationship with air pollution
      in Korea.
AB  - Although analysis of long-term data is necessary to obtain reliable information
      on characteristics of atmospheric visibility and its relationship with air
      pollution, it has rarely been performed. Therefore, a long-term evaluation of
      atmospheric visibility in characteristically different Korean cities, as well as
      a remote island, during 2001 to 2009, was performed in this study. In general,
      visibility decreased in the studied areas during the 9-yr study period. In
      addition, all areas displayed a distinct seasonal trend, with high visibility in
      the cold season relative to the warm season. Weekday visibility, however, did not
      significantly differ from weekend visibility. Similarly, the number of days per
      year for both low (<10 km) and high visibility (>19 km) fluctuated during the
      study period. Busan (a coastal city) exhibited the highest visibility, with an
      overall average of 17.6 km, followed by Daegu (a basin city), Ulsan (with
      concentrated petrochemical industries), Ullungdo (a remote island), and Seoul
      (the capital of Korea). Visibility was found to be significantly correlated with
      target air pollutants, except for ozone, for all metropolitan cities, whereas it
      was significantly correlated only with particulate matter with an aerodynamic
      diameter <10 MUm (PM10) and ozone on the remote island (Ullungdo). Among the
      metropolitan cities, Seoul exhibited the lowest visibility for both the PM10
      standard exceedance and non-exceedance days, followed by Ulsan, Daegu, and Busan.
      The results of this study can be used to establish effective strategies for
      improving urban visibility and air quality. 

PMID- 25603236
TI  - Reversal of radiocontrast medium toxicity in human renal proximal tubular cells
      by white grape juice extract.
AB  - Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical
      problem accounting for 12% of all hospital-acquired cases of acute kidney injury.
      The pathophysiology of CIN is not well understood, but direct toxic effects on
      renal cells have been postulated as contributing to CIN. We have investigated the
      effect of a white grape (Vitis vinifera) juice extract (WGJe) on human renal
      proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium
      diatrizoate. WGJe caused an increase in phosphorylation of the prosurvival
      kinases Akt and ERK1/2 in HK-2 cells. Treatment of HK-2 cells with 75 mgI/ml
      sodium diatrizoate for 2.5h and then further incubation (for 27.5h) after removal
      of the RCM caused a drastic decrease in cell viability. However, pre-treatment
      with WGJe, prior to incubation with diatrizoate, dramatically improved cell
      viability. Analysis of key signaling molecules by Western blotting showed that
      diatrizoate caused a drastic decrease in phosphorylation of Akt (Ser473), FOXO1
      (Thr24) and FOXO3a (Thr32) during the initial 2.5h incubation period, and WGJe
      pre-treatment caused a reversal of these effects. Further analysis by Western
      blotting of samples from HK-2 cells cultured for longer periods of time (for up
      to 27.5h after an initial 2.5h exposure to diatrizoate with or without WGJe pre
      treatment) showed that WGJe pre-treatment caused a negative effect on
      phosphorylation of p38, NF-kappaB (Ser276) and pERK1/2 whilst having a positive
      effect on the phosphorylation of Akt, FOXO1/FOXO3a and maintained levels of Pim-1
      kinase. WGJe may alleviate RCM toxicity through modulation of signaling molecules
      that are known to be involved in cell death and cell survival and its possible
      beneficial effects should be further investigated.

PMID- 25603238
TI  - Anhydrous Ammonia Injection Depth Does Not Affect Nitrous Oxide Emissions in a
      Silt Loam over Two Growing Seasons.
AB  - Anhydrous ammonia (AA) is a major fertilizer source in North America that can
      promote greater emissions of nitrous oxide (NO) than other nitrogen (N)
      fertilizers. Previous studies found that injection of AA at a shallow depth (0.1
      m) decreased NO in a rainfed clay loam but increased NO in an irrigated loamy
      sand compared with the standard injection depth of 0.2 m. The objective of this
      study was to evaluate the effects of AA injection depth in a silt loam soil used
      for corn ( L.) production and managed under two contrasting tillage regimes over
      two consecutive growing seasons (2010 and 2011) in Minnesota. In contrast with
      previous studies, AA placement depth did not affect NO emissions in either
      tillage system or in either growing season. Tillage by itself affected NO
      emissions only in the drier of two seasons, during which NO emissions under no
      tillage (NT) exceeded those under conventional tillage (CT) by 55%. Soil moisture
      content under NT was also greater than under CT only in the drier of the two
      seasons. Effects of AA placement depth and long-term tillage regime on NO
      emissions exhibit intersite as well as interannual variation, which should be
      considered when developing NO mitigation strategies. Further study is needed to
      identify specific soil, climate, or other factors that mediate the contrasting
      responses to management practices across sites. 

PMID- 25603239
TI  - Bioremediation of metal-rich effluents: could the invasive bivalve work as a
      biofilter?
AB  - Industrial effluents are important sources of contamination of water and
      sediments, frequently causing serious damage at different levels of biological
      organization. Management and treatment of harmful industrial wastes is thus a
      major concern. Metal-bearing effluents, such as acid mine drainage (AMD), are
      particularly problematic because metals can easily bioaccumulate in organisms and
      biomagnify across the trophic chain. Several solutions have been proposed to
      treat AMD, including active methods involving the addition of neutralizing agents
      and passive techniques that use natural energy sources for remediation. However,
      increasing environmental and economic requirements lead the constant search for
      more sustainable solutions. The present study explores the possibility of using ,
      an invasive freshwater bivalve, as a bioremediation tool using AMD as a model,
      metal-bearing effluent. The study compares untreated and biotreated effluents at
      two dilution levels (4 and 10% v/v) following two distinct approaches: (i)
      chemical characterization of the metal concentrations in water complemented by
      determination of the accumulation in the clams' soft tissues and shells; and (ii)
      ecotoxicity assessment using standard organisms (the bacterium , the microalgae ,
      and the cladoceran ). Significant removal of metals from water was recorded for
      both effluent dilutions, with higher purification levels found for the 4%
      effluent. The environmental toxicity of the effluents generally decreased after
      the treatment with the clams. Thus, this study provides evidence for the
      suitability of as a bioremediator for metal-bearing effluents, especially if the
      treatment can be materialized in a multistage configuration system. 

PMID- 25603240
TI  - Detection of pathogens, indicators, and antibiotic resistance genes after land
      application of poultry litter.
AB  - Poultry litter (PL) is a by-product of broiler production. Most PL is land
      applied. Land-applied PL is a valuable nutrient source for crop production but
      can also be a route of environmental contamination with manure-borne bacteria.
      The objective of this study was to characterize the fate of pathogens, fecal
      indicator bacteria (FIB), and bacteria containing antibiotic resistance genes
      (ARGs) after application of PL to soils under conventional till or no-till
      management. This 2-yr study was conducted in accordance with normal agricultural
      practices, and microbial populations were quantified using a combination of
      culture and quantitative, real-time polymerase chain reaction analysis. Initial
      concentrations of in PL were 5.4 +/- 3.2 * 10 cells g PL; sp. was not detected in
      the PL but was enriched periodically from PL-amended soils. was detected in PL
      (1.5 +/- 1.3 * 10 culturable or 1.5 +/- 0.3 * 10 genes g) but was rarely detected
      in field soils, whereas enterococci (1.5 +/- 0.5 * 10 cells g PL) were detected
      throughout the study. These results suggest that enterococci may be better FIB
      for field-applied PL. Concentrations of ARGs for sulfonamide, streptomycin, and
      tetracycline resistance increased up to 3.0 orders of magnitude after PL
      application and remained above background for up to 148 d. These data provide new
      knowledge about important microbial FIB, pathogens, and ARGs associated with PL
      application under realistic field-based conditions. 

PMID- 25603241
TI  - Performance of Weibull and Linear Semi-logarithmic Models in Simulating
      Inactivation in Waters.
AB  - Modeling inactivation of indicator microorganisms is a necessary component of
      microbial water quality forecast and management recommendations. The linear semi
      logarithmic (LSL) model is commonly used to simulate the dependencies of
      bacterial concentrations in waters on time. There were indications that
      assumption of the semi-logarithmic linearity may not be accurate enough in
      waters. The objective of this work was to compare performance of the LSL and the
      two-parametric Weibull inactivation models with data on survival of indicator
      organism in various types of water from a representative database of 167
      laboratory experiments. The Weibull model was preferred in >99% of all cases when
      the root mean squared errors and Nash-Sutcliffe statistics were compared.
      Comparison of corrected Akaike statistic values gave the preference to the
      Weibull model in only 35% of cases. This was caused by (i) a small number of
      experimental points on some inactivation curves, (ii) closeness of the shape
      parameter of the Weibull equation to one, and (iii) piecewise log-linear
      inactivation dynamic that could be well described by neither of the two models
      compared. Based on the Akaike test, the Weibull model was favored in
      agricultural, lake, and pristine waters, whereas the LSL model was preferred for
      groundwater, wastewater, rivers, and marine waters. The decimal reduction time
      parameter of both the LSL and Weibull models exhibited an Arrhenius-type
      dependence on temperature. Overall, the existing inactivation data indicate that
      the application of the Weibull model can improve the predictive capabilities of
      microbial water quality modeling. 

PMID- 25603242
TI  - Soil quality assessment for peat-mineral mix cover soil used in oil sands
      reclamation.
AB  - A soil quality (SQ) assessment and rating framework that is quantitative,
      iterative, and adaptable, with justifiable weighting for quality scores, is
      required for evaluating site-specific SQ at land reclamation sites. Such a
      framework needs to identify the minimum dataset that reflects the current
      knowledge regarding relationships between SQ indicators and relevant measures of
      ecosystem performance. Our objective was to develop nonlinear scoring functions
      for assessing the impact on SQ of peat-mineral mix (PMM) used as a cover soil at
      land reclamation sites. Soil functional indicators affected by PMM were extracted
      from existing databases and correlated with soil organic carbon (SOC). Based on
      defined objectives for SQ assessment, indicators with significant correlation ( <
      0.05) to SOC were selected, normalized, and fitted to sigmoid functions using
      nonlinear regression procedure to establish SQ functions (SQFs) that can analyze
      changes in field capacity, permanent wilting point, soil nitrogen, and cation
      exchange capacity of PMM using SOC as input parameter. Application of the SQFs to
      an independent dataset produced ratings with mean differences similar to the
      treatment effects of mixing three levels of peat and mineral soil. These results
      show that derived ratings and weighing factors using SOC reflect the relationship
      between PMM treatment and other SQ indicators. Applying the developed SQFs to a
      long-term soil monitoring dataset shows that an increase or decrease in SOC from
      10 to 20 g kg causes a significant change in SQ. This identifies the need for
      further nutrient and moisture management of PMM to support long-term SQ
      development in land reclamation. 

PMID- 25603243
TI  - Copper and zinc speciation in a biosolids-amended, semiarid grassland soil.
AB  - Predicting trace-metal solid-phase speciation changes associated with long-term
      biosolids land application is important for understanding and improving
      environmental quality. Biosolids were surface-applied (no incorporation; 0, 2.5,
      5, 10, 21, and 30 Mg ha) to a semiarid grassland in 1991 (single application) and
      2002 (repeated application). In July 2003, soils were obtained from the 0- to 8-,
      8- to15-, and 15- to 30-cm depths in all plots. Using soil pH, soluble anion and
      cation concentrations from 0.01 mol L CaCl extractions, dissolved organic C (DOC)
      content, and an estimate of solid phase humic and fulvic acids present, Cu and Zn
      associated with minerals, hydrous ferric oxides (HFO), organically complexed,
      electrostatically bound to organic matter (OM), or DOC phases was modeled using
      Visual Minteq. Scanning electron microscopy and energy-dispersive X-ray analysis
      (SEM-EDXRA) was also used to identify solid-phase metal associations present in
      single and repeated biosolids-amended soils. Based on soil solution chemistry in
      all depths, as modeled using Visual Minteq, >90% of the Cu and >95% of the Zn
      from the single or repeated biosolids-applied soils were sorbed electrostatically
      or as mono- or bidentate solid-phase OM complexes. Up to 10 and 5% of the Cu and
      Zn, respectively, was associated with HFO, with negligible amounts associated
      with DOC. The SEM-EDXRA of clay-sized separates from all soil depths led to
      direct observation of Fe-Cu and Fe-Zn associations. Results implied that after
      surface-applying biosolids either once or twice with up to 30 Mg ha, some shifts
      occurred in phases controlling Cu and Zn solubility, but solution concentrations
      remained below drinking water standards. 

PMID- 25603244
TI  - Influence of dredging on sedimentary arsenic release for a tide-influenced
      waterfront body.
AB  - We evaluated the influence of sediment dredging on sedimentary As release for the
      Inner Lake, a typical tide-influenced waterfront body in the middle to lower
      reaches of the Yangtze River in Zhengjiang, China. By field investigation and
      laboratory experiment, the As content in the deposited sediment before dredging
      was analyzed and the relationship between dynamic disturbance and sedimentary As
      release intensity was established. Using a numerical model in which the factors
      of water current, suspended sediment, and As were coupled, the processes of As
      migration were simulated for typical years and tidal cycles before and after
      dredging. The results show that: (i) the amounts of sedimentary As release during
      the tidal cycles in the flood season and the dry season after dredging were
      reduced by 14.6 and 28.1%, respectively, compared with before dredging; (ii)
      after removal of the surface polluted sediment, the annual volumes of internal
      released As in the high-water year, common-water year, and low-water year were
      decreased to 11.89, 4.94, and 4.89 Mg, respectively; and (iii) the highest
      reduction rate could reach 27.5% in the common-water year, while the lowest was
      10.92% in the high-water year because the massive water exchange with the Yangtze
      River in the high-water year resulted in an enhanced dynamic disturbance that
      played a more dominating role in the internal As release than the surface
      sediment removal. The results of this study may be useful for other researchers
      of water environment protection for waterfront bodies. 

PMID- 25603245
TI  - Lead and cadmium phytoavailability and human bioaccessibility for vegetables
      exposed to soil or atmospheric pollution by process ultrafine particles.
AB  - When plants are exposed to airborne particles, they can accumulate metals in
      their edible portions through root or foliar transfer. There is a lack of
      knowledge on the influence of plant exposure conditions on human bioaccessibility
      of metals, which is of particular concern with the increase in urban gardening
      activities. Lettuce, radish, and parsley were exposed to metal-rich ultrafine
      particles from a recycling factory via field atmospheric fallouts or polluted
      soil. Total lead (Pb) and cadmium (Cd) concentrations in of the edible plant
      parts and their human bioaccessibility were measured, and Pb translocation
      through the plants was studied using Pb isotopic analysis. The Pb and Cd
      bioaccessibility measured for consumed parts of the different polluted plants was
      significantly higher for root exposure (70% for Pb and 89% for Cd in lettuce) in
      comparison to foliar exposure (40% for Pb and 69% for Cd in lettuce). The
      difference in metal bioaccessibility could be linked to the metal
      compartmentalization and speciation changes in relation to exposure conditions.
      Metal nature strongly influences the measured bioaccessibility: Cd presents
      higher bioaccessibility in comparison to Pb. In the case of foliar exposure, a
      significant translocation of Pb from leaves toward the roots was observed. To
      conclude, the type of pollutant and the method of exposure significantly
      influences the phytoavailability and human bioaccessibility of metals, especially
      in relation to the contrasting phenomena involved in the rhizosphere and
      phyllosphere. The conditions of plant exposure must therefore be taken into
      account for environmental and health risk assessment. 

PMID- 25603246
TI  - The role of interior watershed processes in improving parameter estimation and
      performance of watershed models.
AB  - Watershed models typically are evaluated solely through comparison of in-stream
      water and nutrient fluxes with measured data using established performance
      criteria, whereas processes and responses within the interior of the watershed
      that govern these global fluxes often are neglected. Due to the large number of
      parameters at the disposal of these models, circumstances may arise in which
      excellent global results are achieved using inaccurate magnitudes of these "intra
      watershed" responses. When used for scenario analysis, a given model hence may
      inaccurately predict the global, in-stream effect of implementing land-use
      practices at the interior of the watershed. In this study, data regarding
      internal watershed behavior are used to constrain parameter estimation to
      maintain realistic intra-watershed responses while also matching available in
      stream monitoring data. The methodology is demonstrated for the Eagle Creek
      Watershed in central Indiana. Streamflow and nitrate (NO) loading are used as
      global in-stream comparisons, with two process responses, the annual mass of
      denitrification and the ratio of NO losses from subsurface and surface flow, used
      to constrain parameter estimation. Results show that imposing these constraints
      not only yields realistic internal watershed behavior but also provides good in
      stream comparisons. Results further demonstrate that in the absence of
      incorporating intra-watershed constraints, evaluation of nutrient abatement
      strategies could be misleading, even though typical performance criteria are
      satisfied. Incorporating intra-watershed responses yields a watershed model that
      more accurately represents the observed behavior of the system and hence a tool
      that can be used with confidence in scenario evaluation. 

PMID- 25603247
TI  - Nitrogen Retention in a Restored Tidal Stream (Kimages Creek, VA) Assessed by
      Mass Balance and Tracer Approaches.
AB  - Tidal streams are attractive candidates for restoration because of their capacity
      to retain nutrients from upland and estuarine sources. We quantified N retention
      in Kimages Creek, VA, following a dam breach that restored its historical (pre
      1920) connection to the James River Estuary. Estimates of N retention derived
      from mass balance analysis were compared to tracer-based retention estimates
      obtained by injecting NHCl during an incoming tide and measuring recovery on the
      outgoing tide. The injection experiments showed that dissolved inorganic N (DIN)
      retention in the restored tidal and nontidal segments was similar to nearby
      streams and previously published values. These data suggest that the stream has
      attained expected levels of functioning less than 2 yr after restoration despite
      80 yr of impoundment. The mass balance analysis provided additional information
      for restoration assessment as this approach allowed us to track multiple N
      fractions. These results showed that DIN retention was offset by export of total
      organic N resulting in net loss of total N from the restored creek. Seasonal
      variation in DIN retention was significantly and positively related to tidal
      exchange volume and ecosystem metabolism (gross primary production and
      respiration). Our findings show that existing methods for measuring nutrient
      retention in nontidal streams can be adapted to the bidirectional flow patterns
      of tidal streams to assess restoration effectiveness. 

PMID- 25603248
TI  - Stream Sediment Sources in Midwest Agricultural Basins with Land Retirement along
      Channel.
AB  - Documenting the effects of agricultural land retirement on stream-sediment
      sources is critical to identifying management practices that improve water
      quality and aquatic habitat. Particularly difficult to quantify are the effects
      from conservation easements that commonly are discontinuous along channelized
      streams and ditches throughout the agricultural midwestern United States. Our
      hypotheses were that sediment from cropland, retired land, stream banks, and
      roads would be discernible using isotopic and elemental concentrations and that
      source contributions would vary with land retirement distribution along
      tributaries of West Fork Beaver Creek in Minnesota. Channel-bed and suspended
      sediment were sampled at nine locations and compared with local source samples by
      using linear discriminant analysis and a four-source mixing model that evaluated
      seven tracers: In, P, total C, Be, Tl, Th, and Ti. The proportion of sediment
      sources differed significantly between suspended and channel-bed sediment.
      Retired land contributed to channel-bed sediment but was not discernible as a
      source of suspended sediment, suggesting that retired-land material was not
      mobilized during high-flow conditions. Stream banks were a large contributor to
      suspended sediment; however, the percentage of stream-bank sediment in the
      channel bed was lower in basins with more continuous retired land along the
      riparian corridor. Cropland sediments had the highest P concentrations; basins
      with the highest cropland-sediment contributions also had the highest P
      concentrations. Along stream reaches with retired land, there was a lower
      proportion of cropland material in suspended sediment relative to sites that had
      almost no land retirement, indicating less movement of nutrients and sediment
      from cropland to the channel as a result of land retirement. 

PMID- 25603249
TI  - The use of alum to decrease phosphorus losses in runoff from grassland soils.
AB  - Phosphorus (P) loss from land can impair surface water quality. Aluminum sulfate
      (alum)-treated, compared with untreated, manure or slurry decreases P loss when
      applied to land; our hypothesis was that alum may also decrease P loss when
      directly applied to grassland grazed by dairy cows. A rainfall simulation showed
      that alum decreased mean concentrations of filterable reactive P (FRP) by 25 to
      70% and total P (TP) by 20 to 40%, depending on soil P, Al, and Fe concentration
      and alum application rate. Using these factors, we predicted that FRP losses
      would be significantly less from alum-treated grasslands than from untreated
      grasslands for 70 to 96 d. A 14-mo field trial compared runoff P losses from
      plots that received 0, 25, and 50 kg Al ha applied within a week of grazing by
      dairy cattle in spring. Runoff-weighted concentrations (and loads) of FRP and TP
      decreased in alum-treated plots by 47 to 52% and 25 to 34%, respectively. At
      US$157 to US$944 kg P mitigated, cost-effectiveness was estimated as medium to
      low compared with existing strategies for mitigating P loss in dairy farms but
      could be improved if applied to critical source areas of P loss. However,
      additional work, such as determining the need for repeat applications, is
      required before alum can be recommended to decrease P losses from grazed
      grassland. 

PMID- 25603250
TI  - Nutrient and sediment losses in snowmelt runoff from perennial forage and annual
      cropland in the canadian prairies.
AB  - An 8-yr field-scale study, 2005 to 2012, investigated effects of agricultural
      land use on nutrient and sediment losses during snowmelt runoff from four
      treatment fields in southern Manitoba. In 2005, two fields with a long-term
      history of annual crop (AC) production were planted to perennial forage (PF),
      while two other fields were left in AC production. In 2009, the AC fields were
      converted to PF, while the PF fields were returned to AC. Runoff flow rates were
      monitored at the lower edge of the fields, and nutrient concentrations of runoff
      water were determined. The effects of AC and PF on selected variables were
      similar for the spatial (between-fields) and temporal (within-field) comparisons.
      The flow-weighted mean concentrations (FWMCs) and loads of particulate N, P, and
      sediment were not affected by treatment. Soil test N and the FWMC and load of NO
      (NO + NO) were significantly greater in the AC treatment, but the FWMC and load
      of NH were greater in the PF treatment. Loads of total dissolved N (TDN) and
      total N (TN) were not affected by treatment, although the concentrations of TDN
      and TN were greater in the AC treatment. The PF treatment significantly increased
      FWMCs and loads of total dissolved P (TDP) and total P (TP). On an annual
      snowmelt runoff basis, the PF treatment increased the FWMC of TDP by 53% and TP
      by 52% and increased the load of TDP by 221% and TP by 160% compared with the AC
      treatment. The greater P and NH losses in the PF treatment were attributed mainly
      to nutrient release from forage residue due to freezing. 

PMID- 25603251
TI  - Emission reduction of 1,3-dichloropropene by soil amendment with biochar.
AB  - Soil fumigation is an important treatment in the production chain of fruit and
      vegetable crops, but fumigant emissions contribute to air pollution. Biochar as a
      soil amendment has shown the potential to reduce organic pollutants, including
      pesticides, in soils through adsorption and other physicochemical reactions. A
      laboratory column study was performed to determine the effects of soil
      applications of biochar for reducing emissions of the fumigant 1,3
      dichloropropene (1,3-D). The experimental treatments comprised of unamended and
      amended with biochar at doses of 0, 0.5, 1, 2, and 5% (w/w) in the top 5 cm soil
      layer. The unamended treatment resulted in the highest emission peak flux at 48
      to 66 MUg m s. Among the biochar amendment treatments, the highest peak flux
      (0.83 MUg m s) was found in the biochar 0.5% treatment. The total emission loss
      was 35.7 to 40.2% of applied for the unamended treatment and <0.1 to 2.9% for the
      biochar-amendment treatments. A germination bioassay with cucumber seeds showed
      that >=7 d of aeration would be needed to avoid phytotoxicity before replanting
      in biochar-containing fumigated soil. The results indicate that treatments with
      0.5% or more biochar amendment reduced emission peak flux by >99.8% and showed
      total 1,3-D emission loss by >92% compared with that without biochar. The
      amendment of surface soil with biochar shows a great potential for reducing
      fumigant emissions. 

PMID- 25603252
TI  - Sorptive removal of nitro explosives and metals using biochar.
AB  - The feasibility of using biochar as a sorbent to remove nitro explosives and
      metals from contaminated water was investigated through batch experiments.
      Biochar, synthesized using various biomasses, showed a porous structure and a
      high surface area and includes embedded carbonate minerals. Compared with
      granular activated carbon, biochar was competitive as a sorbent for removing Cd,
      Cu, Pb, and Zn from water according to the maximum sorption capacities of the
      metals. Some biochars also effectively sorbed nitro explosives from water.
      Correlation analysis between maximum sorption capacities and properties of
      biochar showed that the sorption capacity of biochar for cationic toxic metals is
      related to cation exchange capacity and that the sorption capacity of explosives
      is proportional to surface area and carbon content. Results from X-ray
      photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses
      and laboratory experiments suggest that surface functional groups may be
      responsible for the sorption of cationic metals to the biochar surface. In
      contrast, carbon contents may account for the sorption of explosives, possibly
      through pi-pi electron donor-acceptor interactions. Our results suggest that
      biochar can be an attractive and alternative option in environmental remediation
      of nitro explosives and metals through sorption and immobilization and that
      appropriate selection of biochar may be necessary according to the types of
      contaminant and the properties of biochar. 

PMID- 25603253
TI  - Differing effects of biosolids on native plants in grasslands of southern british
      columbia.
AB  - The objective of this study was to determine if application of biosolids is
      beneficial for restoring semiarid grasslands. The effects of a one-time surface
      application of biosolids at a rate of 20 Mg ha on individual plant species and
      plant community composition were examined at three degraded semiarid grassland
      sites located in the southern interior of British Columbia, Canada. Biosolids
      application did not result in desirable changes in plant species composition at
      the two drier sites (with annual precipitation <400 mm) yet led to overall
      positive plant species changes at the least dry site (with annual precipitation
      of 400 mm). An important late-seral species of semiarid grasslands, bluebunch
      wheatgrass [ (Pursh) A. Love], did not respond or decreased at the two drier
      sites but increased at the least dry site. Exotic invasive plant species
      increased on all sites. The total vegetative cover of native perennial grasses
      increased from 41 to 99% at the least dry site, with important decreases in low
      growing, early-seral forb species. Although cheatgrass ( L.) was not
      significantly increased by the biosolids treatment, the dominance of cheatgrass
      and lower growing season precipitation at the two drier sites were likely key
      reasons for the poor biosolids restoration success at these sites. Despite some
      concerns, there is potential to use biosolids to restore grassland plant
      communities successfully within 4 or 5 yr on more mesic grassland sites; however,
      biosolids use on drier sites where exotic invasives are present cannot be
      recommended. 

PMID- 25603254
TI  - Conversion of Conservation Tillage to Rotational Tillage to Reduce Phosphorus
      Losses during Snowmelt Runoff in the Canadian Prairies.
AB  - In a preceding study, converting conventional tillage (ConvT) to conservation
      tillage (ConsT) was reported to decrease nitrogen (N) but to increase phosphorus
      (P) losses during snowmelt runoff. A field-scale study was conducted from 2004 to
      2012 to determine if conversion of ConsT to rotational tillage (RotaT), where
      conservation tillage was interrupted by a fall tillage pass every other year,
      could effectively reduce P losses compared with ConsT. The RotaT study was
      conducted on long-term paired watersheds established in 1993. The ConvT field in
      the pair has remained under ConvT practice since 1993, whereas tillage was
      minimized on the ConsT field from 1997 until 2007. In fall 2007, RotaT was
      introduced to the ConsT field, and heavy-duty cultivator passes were conducted in
      the late fall of years 2007, 2009, and 2011. Runoff volume and nutrient content
      were monitored at the edge of the two fields, and soil and crop residue samples
      were taken in each field. Greater soil Olsen P and more P released from crop
      residue are likely the reasons for the increased P losses in the ConsT treatment
      (2004-2007) relative to the ConvT treatment (2004-2007). Analysis of covariance
      indicated that, compared with ConsT (2004-2007), RotaT (2008-2012) increased the
      concentrations of dissolved organic carbon (DOC) by 62%, total dissolved N (TDN)
      by 190%, and total N (TN) by 272% and increased the loads of DOC by 34%, TDN by
      34%, and TN by 60%. However, RotaT (2008-2012) decreased soil test P in surface
      soil, P released from crop residue, and duration of runoff compared with ConsT
      (2004-2007) and thus decreased the concentrations of total dissolved P (TDP) by
      46% and total P (TP) by 38% and decreased the loads of TDP by 56% and TP by 42%.
      In the Canadian Prairies, where P is a major environmental concern compared with
      N, RotaT was demonstrated to be an effective practice to reduce P losses compared
      with ConsT. 

PMID- 25603255
TI  - Land use change impacts on water quality in three lake winnipeg watersheds.
AB  - Lake Winnipeg eutrophication results from excess nutrient loading due to
      agricultural activities across the watershed. Estimating nonpoint-source
      pollution and the mitigation effects of beneficial management practices (BMPs) is
      an important step in protecting the water quality of streams and receiving
      waters. The use of computer models to systematically compare different landscapes
      and agricultural systems across the Red-Assiniboine basin has not been attempted
      at watersheds of this size in Manitoba. In this study, the Soil and Water
      Assessment Tool was applied and calibrated for three pilot watersheds of the Lake
      Winnipeg basin. Monthly flow calibration yielded overall satisfactory Nash
      Sutcliffe efficiency (NSE), with values above 0.7 for all simulations. Total
      phosphorus (TP) calibration NSE ranged from 0.64 to 0.76, total N (TN) ranged
      from 0.22 to 0.75, and total suspended solids (TSS) ranged from 0.29 to 0.68.
      Based on the assessment of the TP exceedance levels from 1993 to 2007, annual
      loads were above proposed objectives for the three watersheds more than half of
      the time. Four BMP scenarios based on land use changes were studied in the
      watersheds: annual cropland to hay land (ACHL), wetland restoration (WR),
      marginal annual cropland conversion to hay land (MACHL), and wetland restoration
      on marginal cropland (WRMAC). Of these land use change scenarios, ACHL had the
      greatest impact: TSS loads were reduced by 33 to 65%, TN by 58 to 82%, and TP by
      38 to 72% over the simulation period. By analyzing unit area and percentage of
      load reduction, the results indicate that the WR and WRMAC scenarios had a
      significant impact on water quality in high loading zones in the three
      watersheds. Such reductions of sediment, N, and P are possible through land use
      change scenarios, suggesting that land conservation should be a key component of
      any Lake Winnipeg restoration strategy. 

PMID- 25603256
TI  - A national survey of trace organic contaminants in Australian rivers.
AB  - Trace organic contaminant (TrOC) studies in Australia have, to date, focused on
      wastewater effluents, leaving a knowledge gap of their occurrence and risk in
      freshwater environments. This study measured 42 TrOCs including industrial
      compounds, pesticides, and pharmaceuticals and personal care products by liquid
      chromatography tandem mass spectrometry at 73 river sites across Australia
      quarterly for 1 yr. Trace organic contaminants were found in 92% of samples, with
      a median of three compounds detected per sample (maximum 18). The five most
      commonly detected TrOCs were the pharmaceuticals salicylic acid (82%, maximum =
      1530 ng/L), paracetamol (also known as acetaminophen; 45%, maximum = 7150 ng/L),
      and carbamazepine (27%, maximum = 682 ng/L), caffeine (65%, maximum = 3770 ng/L),
      and the flame retardant (2-chloroethyl) phosphate (44%, maximum = 184 ng/L).
      Pesticides were detected in 28% of the samples. To determine the risk posed by
      the detected TrOCs to the aquatic environment, hazard quotients were calculated
      by dividing the maximum concentration detected for each compound by the predicted
      no-effect concentrations. Three of the 42 compounds monitored (the
      pharmaceuticals carbamazepine and sulfamethoxazole and the herbicide simazine)
      had a hazard quotient >1, suggesting that they may be causing adverse effects at
      the most polluted sites. A further 10 compounds had hazard quotients >0.1,
      indicating a potential risk; these included four pharmaceuticals, three personal
      care products, and three pesticides. Most compounds had hazard quotients
      significantly <0.1. The number of TrOCs measured in this study was limited and
      further investigations are required to fully assess the risk posed by complex
      mixtures of TrOCs on exposed biota. 

PMID- 25603257
TI  - Monitoring design for assessing compliance with numeric nutrient standards for
      rivers and streams using geospatial variables.
AB  - Implementation of numeric nutrient standards in Colorado has prompted a need for
      greater understanding of human impacts on ambient nutrient levels. This study
      explored the variability of annual nutrient concentrations due to upstream
      anthropogenic influences and developed a mathematical expression for the number
      of samples required to estimate median concentrations for standard compliance. A
      procedure grounded in statistical hypothesis testing was developed to estimate
      the number of annual samples required at monitoring locations while taking into
      account the difference between the median concentrations and the water quality
      standard for a lognormal population. For the Cache La Poudre River in northern
      Colorado, the relationship between the median and standard deviation of total N
      (TN) and total P (TP) concentrations and the upstream point and nonpoint
      concentrations and general hydrologic descriptors was explored using multiple
      linear regression models. Very strong relationships were evident between the
      upstream anthropogenic influences and annual medians for TN and TP ( > 0.85, <
      0.001) and corresponding standard deviations ( > 0.7, < 0.001). Sample sizes
      required to demonstrate (non)compliance with the standard depend on the measured
      water quality conditions. When the median concentration differs from the standard
      by >20%, few samples are needed to reach a 95% confidence level. When the median
      is within 20% of the corresponding water quality standard, however, the required
      sample size increases rapidly, and hundreds of samples may be required. 

PMID- 25603258
TI  - Nutrients and sediments in surface runoff water from direct-seeded rice fields:
      implications for nutrient budgets and water quality.
AB  - Nutrient losses from rice fields can have economic and environmental
      consequences. Little is known about nutrient losses in surface runoff waters from
      direct-seeded rice systems, which are common in the United States and
      increasingly more so in Asia. The objectives of this research were to quantify
      nutrient losses from California rice fields in surface runoff waters and to
      determine when and under what conditions losses are greatest. Research was
      conducted in 10 rice fields varying in residue (burned or incorporated) and water
      management over a 2-yr period. Concentrations of NH-N and NO-N in runoff water
      across sites, seasons, and management practices averaged <0.1 mg N L. Runoff
      water PO-P concentration averaged 0.14 mg L and was not affected by season or
      straw management practices. However, P fluxes were higher in the winter when rice
      straw was burned (2.59 kg ha) as opposed to incorporated (0.44 kg ha). Average
      seasonal runoff water K concentrations did not vary with season and straw
      management, although they were highest at the onset of the winter season. Average
      total suspended solids (TSS) concentrations did not vary by season but were
      highest during the winter in the straw-incorporated fields (46 mg L). Rice fields
      were sinks for K (4.9 kg K ha) during the growing season. Fields were not
      significant sources of nutrients or TSS during the growing season; however,
      during the winter fallow they could be sources of NH-N, P, K, and TSS, especially
      as water fluxes from fields increased. 

PMID- 25603259
TI  - Spatial characterization of riparian buffer effects on sediment loads from
      watershed systems.
AB  - Understanding all watershed systems and their interactions is a complex, but
      critical, undertaking when developing practices designed to reduce topsoil loss
      and chemical/nutrient transport from agricultural fields. The presence of
      riparian buffer vegetation in agricultural landscapes can modify the
      characteristics of overland flow, promoting sediment deposition and nutrient
      filtering. Watershed simulation tools, such as the USDA-Annualized Agricultural
      Non-Point Source (AnnAGNPS) pollution model, typically require detailed
      information for each riparian buffer zone throughout the watershed describing the
      location, width, vegetation type, topography, and possible presence of
      concentrated flow paths through the riparian buffer zone. Research was conducted
      to develop GIS-based technology designed to spatially characterize riparian
      buffers and to estimate buffer efficiency in reducing sediment loads in a
      semiautomated fashion at watershed scale. The methodology combines modeling
      technology at different scales, at individual concentrated flow paths passing
      through the riparian zone, and at watershed scales. At the concentrated flow path
      scale, vegetative filter strip models are applied to estimate the sediment
      trapping efficiency for each individual flow path, which are aggregated based on
      the watershed subdivision and used in the determination of the overall impact of
      the riparian vegetation at the watershed scale. This GIS-based technology is
      combined with AnnAGNPS to demonstrate the effect of riparian vegetation on
      sediment loadings from sheet and rill and ephemeral gully sources. The effects of
      variability in basic input parameters used to characterize riparian buffers, onto
      generated outputs at field scale (sediment trapping efficiency) and at watershed
      scale (sediment loadings from different sources) were evaluated and quantified.
      The AnnAGNPS riparian buffer component represents an important step in
      understanding and accounting for the effect of riparian vegetation, existing
      and/or managed, in reducing sediment loads at the watershed scale. 

PMID- 25603260
TI  - Assessment of selected bioretention blends for nutrient retention using mesocosm
      experiments.
AB  - This study compares the performance of three bioretention media blends for N and
      P removal from simulated urban runoff in experimental mesocosms. TerraSolve,
      Biofilter, and "VT Mix" (Virginia Tech) were compared with and without vegetation
      at varying hydraulic residence times (HRTs). Adsorption isotherm experiments were
      also conducted. TerraSolve and VT Mix included water treatment residuals (WTRs),
      Biofilter and VT Mix included yard-waste compost (YWC), and TerraSolve included a
      mix of coir and peat. TerraSolve removed the highest amount of total P (>95%),
      which is attributed to the high quantity of WTRs. Results were similar for VT
      Mix, likely due to WTR content. Adsorption isotherms indicate a substantial
      difference due to this factor. Vegetative mesocosms were found to be less
      effective at P removal at an HRT of 6 to 12 h but not at an HRT of 24 h. VT Mix
      had the highest removal of total Kjeldahl nitrogen (TKN), significantly different
      than the other blends. Interactive effects with vegetation were observed,
      generally improving TKN removal at all HRTs, with the highest at 24 h.
      Substantial export of nutrients when using compost was not observed. The addition
      of YWC appeared to increase N removal, possibly by denitrification. It is
      recommended that bioretention media contain <10% fines, a source of amorphous Al
      for P adsorption, at least 3 to 5% total organic C in the form of a low P,
      relatively stable compost, and a minimum concentration of plant-available
      nutrients for establishment of vegetation. For systems that use HRT, optimum
      residence time is influenced by media composition. 

PMID- 25603261
TI  - Field-scale Variation in Colloid Dispersibility and Transport: Multiple Linear
      Regressions to Soil Physico-Chemical and Structural Properties.
AB  - Water-dispersible soil colloids (WDC) act as carriers for sorbing chemicals in
      macroporous soils and hence constitute a significant risk for the aquatic
      environment. The prediction of WDC readily available for facilitated chemical
      transport is an unsolved challenge. This study identifies key parameters and
      predictive indicators for assessing field-scale variation of WDC. Samples
      representing three measurement scales (1- to 2-mm aggregates, intact 100-cm
      rings, and intact 6283 cm columns) were retrieved from the topsoil of a 1.69-ha
      agricultural field in a 15-m by 15-m grid to determine colloid dispersibility,
      mobilization, and transport. The amount of WDC was determined using (i) a laser
      diffraction method on 1- to 2-mm aggregates and (ii) an end-over-end shaking
      method on 100-cm intact rings. The accumulated amount of colloids leached from 20
      cm by 20-cm intact columns was determined as a measure of the integrated colloid
      mobilization and transport. The WDC and the accumulated colloid transport were
      higher in samples from the northern part of the field. Using multiple linear
      regression (MLR) analyses, WDC or amount of colloids transported were predicted
      at the three measurement scales from 24 measured, geo-referenced parameters to
      identify parameters that could serve as indicator parameters for screening for
      colloid dispersibility, mobilization, and transport. The MLR analyses were
      performed at each sample scale using all, only northern, and only southern field
      locations. Generally, the predictive power of the regression models was best on
      the smallest 1- to 2-mm aggregate scale. Overall, our results suggest that
      different drivers controlled colloid dispersibility and transport at the three
      measurement scales and in the two subareas of the field. 

PMID- 25603262
TI  - Heavy-Metal Fractions in Solid and Liquid Separates of Swine Slurry Separated
      using Different Technologies.
AB  - Accumulation of metals is a concern with continuous application of swine slurry
      to agricultural soils. Solid-liquid separation is a promising approach for
      reducing phosphorus and total metal loadings with swine manure application to
      farmlands. However, very little work has been performed on the partitioning of
      different metal fractions in swine slurry to separated solids and liquids. This
      study examined the distribution of various metal fractions in raw manures (RM),
      their separated liquids (SL), and separated solids (SS). The three separation
      techniques used were centrifuge without flocculant (CNF), centrifuge with
      flocculant (CFL), and rotary press with flocculant (RFL). Concentrations of Cd,
      Cu, Zn, Ni, and Se in manure and separates were determined by a modified
      Sposito's sequential chemical fractionation scheme to extract water-soluble,
      exchangeable, organically bound, carbonate-precipitated, and residual fractions.
      The greatest concentrations of metals were recovered in the residual fraction,
      with the organically bound and carbonate-precipitated concentrations much greater
      than water-soluble and exchangeable fractions. Separation index () (i.e.,
      percentage partitioned to SS) ranged from 13 to 66%, 9 to 87%, 16 to 93%, and 23
      to 96% for water-soluble, exchangeable, organically bound, and carbonate
      precipitated fractions, respectively. The values in general, were significantly (
      < 0.05) greater for flocculant-based separation techniques than for CNF. For
      organically bound and carbonate-precipitated fractions, the greatest was obtained
      with the RFL for most metals. Our results suggest that applying the SL from RFL
      separation would minimize metal loading to farmlands compared with SL from CNF
      and CFL techniques. However, further validation is required using more sources of
      manure and different flocculants. 

PMID- 25603263
TI  - Effect of hydrothermally carbonized char application on trace gas emissions from
      two sandy soil horizons.
AB  - The application of biochar to soil is a potential tool for the long-term
      sequestration of C and a possible mitigation of greenhouse gas (GHG) emissions.
      Among the various processes available to produce biochar, hydrothermal
      carbonization is one technique that is suitable for moist feedstock like
      digestates from biogas production. The aim of this study was to investigate the
      stability of C and emissions of NO after the addition of (i) digested wheat ( L.)
      straw (digestate) and (ii) hydrothermally carbonized (HTC) char of wheat straw as
      well as (iii) HTC char of digested wheat straw to two soil horizons that differed
      in C content. The HTC chars were obtained from wheat straw and digested wheat
      straw that were hydrothermally carbonized at 230 degrees C for 6 h. The digestate
      and HTC chars were mixed with soil and incubated in 125-mL vessels. The GHG
      emissions of CO and NO were measured at regular intervals. Additionally, after
      108 d, N was applied in the form of NHNO equivalent to 100 kg N ha. After 500 d
      of incubation, the digestate had lost 34% of C, while the soil mixture with the
      corresponding HTC char lost 12% of C in the form of CO from the topsoil. The
      estimated bi-exponential half-life of the recalcitrant C was more than 50% longer
      for the carbonized material than for the untreated digestate. The NO emissions
      from both HTC chars were significantly reduced compared with untreated digestate.
      The reductions were up to 64% for the topsoil and 60% for the subsoil samples.
      These laboratory results show that HTC holds the potential to increase the C
      stability of fermented and carbonized biomasses and to reduce NO emissions. 

PMID- 25603264
TI  - Co-composting of Beef Cattle Feedlot Manure with Construction and Demolition
      Waste.
AB  - With increased availability of dried distillers' grains with solubles (DDGS) as
      cattle feed and the need to recycle organic wastes, this research investigated
      the feasibility of co-composting DDGS cattle feedlot manure with construction and
      demolition (C&D) waste. Manure was collected from cattle fed a typical western
      Canadian finishing diet (CK) of 860 g rolled barley ( L.) grain, 100 g barley
      silage, and 40 g vitamin and mineral supplement kg dry matter (DM) and from
      cattle fed the same diet but (DG manure) with 300 g kg DM barley grain being
      replaced by DDGS. The CK and DG manures were co-composted with and without C&D
      waste in 13 m bins. Compost materials were turned on Days 14, 37, and 64, and
      terminated on Day 99. Adding C&D waste led to higher compost temperatures (0.4 to
      16.3 degrees C, average 7.2 degrees C) than manure alone. Final composts had
      similar total C, total N, C/N ratios, and water-extractable K, Mg, and NO content
      across all treatments. However, adding C&D waste increased deltaC, deltaN, water
      extractable SO, and Ca contents and decreased pH, total P (TP), water-extractable
      C, N, and P and most volatile fatty acids (VFA). The higher C&D compost
      temperatures should reduce pathogens while reduced VFA content should reduce
      odors. When using the final compost product, the increased SO and reduced TP and
      available N and P content in C&D waste compost should be taken into
      consideration. Increased S content in C&D compost may be beneficial for some
      crops grown on S-deficient soils. 

PMID- 25603265
TI  - Spatial oxygen distribution and nitrous oxide emissions from soil after manure
      application: a novel approach using planar optodes.
AB  - The availability and spatial distribution of oxygen (O) in agricultural soil are
      controlling factors in the production and emission of nitrous oxide (NO) to the
      atmosphere, but most experiments investigating the effects of various factors on
      NO emissions in soil have been conducted without determining the content and
      distribution of O. This complicates data interpretation and leads to speculative
      conclusions about which nitrogen transformation processes are responsible for NO
      production. Using an O-specific planar optode, this paper shows how
      spatiotemporal O dynamics can be used to interpret data on NO emissions following
      a uniform or layered amendment of manure to agricultural soil. The spatial
      distribution of O and gas emission rates were monitored for 12 h. An anoxic layer
      formed rapidly around the layered manure, whereas the uniformly distributed
      manure led to a more widespread anoxia. Nitrous oxide emissions increased
      immediately after depletion of O in the manure-amended treatments. Greater
      understanding and improved knowledge of the spatial distribution of O is clearly
      beneficial and can be used to devise improved application strategies for
      mitigating NO emissions from manure and other fertilizers. 

PMID- 25603266
TI  - Salt Marsh Sediment Biogeochemical Response to the BP Blowout.
AB  - The impact of the blowout on salt marshes was investigated by observing the
      biogeochemistry in salt marsh sediments along the Gulf Coast. High sulfide levels
      due to hydrocarbon loading, increased microbial activity, and microbial community
      shifts can lead to plant browning and mortality. Sediment biogeochemical
      processes that degrade enriched carbon pools through sulfate reduction are
      primarily responsible for the biodegradation of spilled hydrocarbons. An
      assessment of the impact of contamination on salt marshes at Skiff Island, LA,
      and Cat Island, Marsh Point, and Saltpan Island, MS, was achieved through
      sediment electrode profiling, microbial community profiling, and quantification
      of hydrocarbon contamination, which captured the spatial sedimentary
      biogeochemical response that affects salt marsh productivity. At western
      locations (Skiff and Cat Islands), total petroleum hydrocarbons (TPHs) ranged
      from 2183 to 2996 mg kg, which was more than double the TPH concentration
      observed at eastern locales. At eastern study locations (e.g., Marsh Point),
      sedimentary pore-water HS concentrations were higher (maximum value = 231 mg L)
      and detected further up in the sediment column than at western locales (e.g.,
      Skiff Island). Similarly, anaerobic and aerobic microbial activity, as measured
      by C substrate utilization profiles and well-color development, was as high or
      higher at eastern locations as compared with western locations. These results
      indicate that other factors besides location or degree of contamination, perhaps
      sedimentary dynamics and physical processes specific to each marsh, should be
      considered when determining salt marsh response to hydrocarbon contamination. 

PMID- 25603267
TI  - Managing Agricultural Greenhouse Gases: Coordinated Agricultural Research through
      GRACEnet to Address Our Changing Climate.

PMID- 25603270
TI  - Glyceraldehyde-3-phosphate dehydrogenase is required for efficient repair of
      cytotoxic DNA lesions in Escherichia coli.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional protein
      with diverse biological functions in human cells. In bacteria, moonlighting GAPDH
      functions have only been described for the secreted protein in pathogens or
      probiotics. At the intracellular level, we previously reported the interaction of
      Escherichia coli GAPDH with phosphoglycolate phosphatase, a protein involved in
      the metabolism of the DNA repair product 2-phosphoglycolate, thus suggesting a
      putative role of GAPDH in DNA repair processes. Here, we provide evidence that
      GAPDH is required for the efficient repair of DNA lesions in E. coli. We show
      that GAPDH-deficient cells are more sensitive to bleomycin or methyl
      methanesulfonate. In cells challenged with these genotoxic agents, GAPDH
      deficiency results in reduced cell viability and filamentous growth. In addition,
      the gapA knockout mutant accumulates a higher number of spontaneous abasic sites
      and displays higher spontaneous mutation frequencies than the parental strain.
      Pull-down experiments in different genetic backgrounds show interaction between
      GAPDH and enzymes of the base excision repair pathway, namely the AP-endonuclease
      Endo IV and uracil DNA glycosylase. This finding suggests that GAPDH is a
      component of a protein complex dedicated to the maintenance of genomic DNA
      integrity. Our results also show interaction of GAPDH with the single-stranded
      DNA binding protein. This interaction may recruit GAPDH to the repair sites and
      implicates GAPDH in DNA repair pathways activated by profuse DNA damage, such as
      homologous recombination or the SOS response. 

PMID- 25603271
TI  - AGE/RAGE signalling regulation by miRNAs: associations with diabetic
      complications and therapeutic potential.
AB  - Excessive formation of advanced glycation end-products (AGEs) presents the most
      important mechanism of metabolic memory that underlies the pathophysiology of
      chronic diabetic complications. Independent of the level of hyperglycaemia, AGEs
      mediate intracellular glycation of the mitochondrial respiratory chain proteins
      leading to excessive production of reactive oxygen species (ROS) and
      amplification of their formation. Additionally, AGEs trigger intracellular damage
      via activation of the receptor for AGEs (RAGE) signalling axis that leads to
      elevation of cytosolic ROS, nuclear factor kappaB (NF-kappaB) activation,
      increased expression of adhesion molecules and cytokines, induction of oxidative
      and endoplasmic reticulum stress. Recent studies have identified novel microRNAs
      (miRNAs) involved in the regulation of AGE/RAGE signalling in the context of
      diabetic micro- and macrovascular complications. The aim of this review is to
      discuss the emerging role of miRNAs on AGE/RAGE pathway and the potential use of
      several miRNAs as novel therapeutic targets. 

PMID- 25603272
TI  - Primary failure rate for 1680 extra-alveolar mandibular buccal shelf mini-screws
      placed in movable mucosa or attached gingiva.
AB  - OBJECTIVE: To compare the initial failure rate (<=4 months) for extra-alveolar
      mandibular buccal shelf (MBS) miniscrews placed in movable mucosa (MM) or
      attached gingiva (AG). MATERIALS AND METHODS: A total of 1680 consecutive
      stainless steel (SS) 2 * 12-mm MBS miniscrews were placed in 840 patients (405
      males and 435 females; mean age, 16 +/- 5 years). All screws were placed lateral
      to the alveolar process and buccal to the lower first and second molar roots. The
      screw heads were at least 5 mm superior to the soft tissue. Loads from 8 oz-14 oz
      (227 g-397 g, 231-405 cN) were used to retract the mandibular buccal segments for
      at least 4 months. RESULTS: Overall, 121 miniscrews out of 1680 (7.2%) failed:
      7.31% were in MM and 6.85% were in AG (statistically insignificant difference).
      Failures were unilateral in 89 patients and bilateral in 16. Left side (9.29%)
      failures was significantly greater (P < .001) compared with those on the right
      (5.12%). Average age for failure patients was 14 +/- 3 years. CONCLUSION: MBS
      miniscrews were highly successful (approximately 93%), but there was no
      significant difference between placement in MM or AG. Failures were more common
      on the patient's left side and in younger adolescent patients. Having 16 patients
      with bilateral failures suggests that a small fraction of patients (1.9%) are
      predisposed to failure with this method.

PMID- 25603273
TI  - Response criteria for malignant lymphoma.
AB  - In the last 35 years, many attempts have been made to define criteria for the
      assessment of treatment response in malignant lymphoma. These systems, with
      respect to both morphological and molecular imaging, aim to standardize scan
      results, in order to simplify the interpretation of findings, facilitate
      multicentric research trials, and compare published data. Unfortunately, there is
      no consensus among the main international hematological associations on which
      criteria are the most appropriate. This detailed and comprehensive description of
      all classifications intends to focus attention on this topic. 

PMID- 25603274
TI  - Rapid calcitriol increase and persistent calcidiol insufficiency in the first 6
      months after kidney transplantation.
AB  - INTRODUCTION: Vitamin D deficiency or insufficiency is prevalent in kidney
      transplant recipients. Little is known about post-transplantation changes in
      vitamin D forms, which are essential for bone health and other health outcomes.
      The aim was to measure the levels of calcidiol and calcitriol during the first 6
      months after kidney transplantation and examine their relation with other bone
      mineral metabolic parameters. PATIENTS AND METHODS: A prospective study was
      performed on 98 patients recruited between April 2010 and June 2011. Calcidiol
      and calcitriol levels were measured at baseline and at days 15, 30, 90, and 180
      after kidney transplantation. RESULTS: Serum calcidiol levels remained
      persistently low: 14.3 (9-22) ng/ml at baseline and 16.3 (10.1-20.6) ng/ml at 6
      months (P=0.641). At 6 months, calcidiol levels showed an inverse correlation
      with simultaneously measured parathyroid hormone levels. Calcidiol showed a trend
      to be higher in patients transplanted in spring but with no statistically
      significant difference. Calcitriol levels increased from 17 (13-23.7) pg/ml at
      baseline to 24 (16-32) pg/ml (P=0.002) in the first 2 weeks after transplantation
      and reached 37 (25-50) pg/ml (P=0.000) after 6 months. During the follow-up,
      calcitriol levels showed a significant inverse correlation with baseline
      fibroblast growth factor-23 levels. At month 6, calcitriol levels were inversely
      correlated with baseline fibroblast growth factor-23 levels and directly
      correlated with calcidiol levels. CONCLUSION: In most patients, calcidiol levels
      remain low 6 months after kidney transplantation, whereas calcitriol levels
      rapidly return to normal. Lower calcidiol blood levels promoted lower calcitriol
      blood levels and higher parathyroid hormone concentrations.

PMID- 25603275
TI  - Potential values of metabolic tumor volume and heterogeneity measured with 18F
      FDG PET/CT pretreatment to evaluate local control for esophageal squamous cell
      carcinoma treated with nonsurgical therapy.
AB  - OBJECTIVES: The aim of the study was to evaluate the predictive value of fluorine
      18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) pretreatment on local
      control (LC) and survival after radical radiotherapy or chemoradiotherapy in
      patients with locally advanced esophageal squamous cell carcinoma (SCC) and to
      discuss its potential value for establishing optimal radiation treatment plans.
      METHODS: Fifty-eight patients with pathologically proven esophageal SCC who
      underwent 18F-FDG PET/CT pretreatment in our center were retrospectively
      reviewed. We examined the correlation between the PET parameters of primary
      tumors and LC and overall survival. The coefficient of variation was used to
      estimate the 18F-FDG uptake in heterogeneity. RESULTS: The mean duration of
      follow-up for surviving patients was 38 months, and 36 patients died because of
      tumor recurrence or other diseases. The rates of 3-year overall survival and LC
      were 40.4 and 50.4%, respectively. Multivariate analysis of LC revealed that
      metabolic tumor volume (MTV) greater than 16.08 ml was the only predictor of
      outcome, with a lower 3-year LC (P=0.017, hazard ratio: 1.608, 95% confidence
      interval: 1.090-2.371). The coefficient of variations of their primary lesion
      were higher compared with those of patients who had smaller MTVs. CONCLUSION: In
      this study, MTV assessed by PET/CT might be an adverse factor for predicting LC
      in esophageal SCC. For those with higher MTVs, higher intratumor heterogeneity
      suggests that irradiation may need to be boosted in stable high-uptake regions to
      improve LC. These results need to be prospectively validated in larger cohorts.

PMID- 25603277
TI  - Global Harmonization of Maximum Residue Limits for Pesticides.
AB  - International trade plays an important role in national economics. The Codex
      Alimentarius Commission develops harmonized international food standards,
      guidelines, and codes of practice to protect the health of consumers and to
      ensure fair practices in the food trade. The Codex maximum residue limits (MRLs)
      elaborated by the Codex Committee on Pesticide Residues are based on the
      recommendations of the FAO/WHO Joint Meeting on Pesticides (JMPR). The basic
      principles applied currently by the JMPR for the evaluation of experimental data
      and related information are described together with some of the areas in which
      further developments are needed. 

PMID- 25603278
TI  - van der Waals epitaxial ultrathin two-dimensional nonlayered semiconductor for
      highly efficient flexible optoelectronic devices.
AB  - Despite great progress in synthesis and application of graphene-like materials,
      it remains a considerable challenge to prepare two-dimensional (2D)
      nanostructures of nonlayered materials that may bring us surprising physical and
      chemical properties. Here, we propose a general strategy for the growth of 2D
      nonlayered materials by van der Waals epitaxy (vdWE) growth with two conditions:
      (1) the nonlayered materials satisfy 2D anisotropic growth and (2) the growth is
      implemented on the van der Waals substrates. Large-scale ultrathin 2D Pb(1
      x)Sn(x)Se nanoplates (~15-45 nm) have been produced on mica sheets by applying
      this strategy. Benefiting from the 2D geometry of Pb(1-x)Sn(x)Se nanoplates and
      the flexibility of mica sheet, flexible photodetectors that exhibit fast,
      reversible, and stable photoresponse and broad spectra detection ranging from UV
      to infrared light (375, 473, 632, 800, and 980 nm) are in situ fabricated based
      on Pb(1-x)Sn(x)Se nanoplates. We anticipate that more nonlayered materials will
      be developed into 2D nanostructures through vdWE, enabling the exploitation of
      novel electronic and optoelectronic devices.

PMID- 25603276
TI  - The mitochondrial uniporter controls fight or flight heart rate increases.
AB  - Heart rate increases are a fundamental adaptation to physiological stress, while
      inappropriate heart rate increases are resistant to current therapies. However,
      the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker
      cells remain incompletely understood. The mitochondrial calcium uniporter (MCU)
      facilitates calcium entry into the mitochondrial matrix to stimulate metabolism.
      We developed mice with myocardial MCU inhibition by transgenic expression of a
      dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting
      heart rates but were incapable of physiological fight or flight heart rate
      acceleration. We found that MCU function was essential for rapidly increasing
      mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative
      phoshorylation was required to accelerate reloading of an intracellular calcium
      compartment before each heartbeat. Our findings show that MCU is necessary for
      complete physiological heart rate acceleration and suggest that MCU inhibition
      could reduce inappropriate heart rate increases without affecting resting heart
      rate. 

PMID- 25603279
TI  - The importance of sonographer experience and machine quality with regards to the
      role of musculoskeletal ultrasound in routine care of rheumatoid arthritis
      patients.
AB  - OBJECTIVES: Regarding recent progress, musculoskeletal ultrasound (US) will
      probably soon be integrated in standard care of patient with rheumatoid arthritis
      (RA). However, in daily care, quality of US machines and level of experience of
      sonographers are varied. We conducted a study to assess reproducibility and
      feasibility of an US scoring for RA, including US devices of different quality
      and rheumatologist with various levels of expertise in US as it would be in daily
      care. METHODS: The Swiss Sonography in Arthritis and Rheumatism (SONAR) group has
      developed a semi-quantitative score using OMERACT criteria for synovitis and
      erosion in RA. The score was taught to 108 rheumatologists trained in US. One
      year after the last workshop, 19 rheumatologists participated in the study. Scans
      were performed on 6 US machines ranging from low to high quality, each with a
      different patient. Weighted kappa was calculated for each pair of readers.
      RESULTS: Overall, the agreement was fair to moderate. Quality of device,
      experience of the sonographers and practice of the score before the study
      improved substantially the agreement. Agreement assessed on higher quality
      machine, among sonographers with good experience in US increased to substantial
      (median kappa for B-mode and Doppler: 0.64 and 0.41 for erosion). CONCLUSIONS:
      This study demonstrated feasibility and reproducibility of the Swiss US SONAR
      score for RA. Our results confirmed importance of the quality of US machine and
      the training of sonographers for the implementation of US scoring in the routine
      daily care of RA.

PMID- 25603280
TI  - Characterization of the gila monster (Heloderma suspectum suspectum) venom
      proteome.
AB  - The archetypical venomous lizard species are the helodermatids, the gila monsters
      (Heloderma suspectum) and the beaded lizards (Heloderma horridum). In the present
      study, the gila monster venom proteome was characterized using 2D-gel
      electrophoresis and tandem mass spectrometry-based de novo peptide sequencing
      followed by protein identification based on sequence homology. A total of 39
      different proteins were identified out of the 58 selected spots that represent
      the major constituents of venom. Of these proteins, 19 have not previously been
      identified in helodermatid venom. The data showed that helodermatid venom is
      complex and that this complexity is caused by genetic isoforms and post
      translational modifications including proteolytic processing. In addition, the
      venom proteome analysis revealed that the major constituents of the gila monster
      venom are kallikrein-like serine proteinases (EC 3.4.21) and phospholipase A2
      (type III) enzymes (EC 3.1.1.4). A neuroendocrine convertase 1 homolog that most
      likely converts the proforms of the previously identified bioactive exendins into
      the mature and active forms was identified suggesting that these peptide toxins
      are secreted as proforms that are activated by proteolytic cleavage following
      secretion as opposed to being activated intracellularly. The presented global
      protein identification-analysis provides the first overview of the helodermatid
      venom composition. BIOLOGICAL SIGNIFICANCE: The helodermatid lizards are the
      classical venomous lizards, and the pharmacological potential of the venom from
      these species has been known for years; best illustrated by the identification of
      exendin-4, which is now used in the treatment of type 2 diabetes. Despite the
      potential, no global analyses of the protein components in the venom exist. A
      hindrance is the lack of a genome sequence because it prevents protein
      identification using a conventional approach where MS data are searched against
      predicted protein sequences based on the genome sequence. However, in the recent
      years the development of software tools for de novo sequencing and homology
      searches have improved significantly facilitating the first global analysis of
      the major protein components of helodermatid venom presented in this study. We
      have used a 2D-gel approach and determined the protein components in the 58 major
      spots resulting in the identification of 39 unique proteins. Of these, 19 have
      not previously been identified in helodermatid venom. The analysis provides
      results with impact on our understanding of the function and evolution of venom
      proteins, and serves as a basis for further unraveling of the pharmaceutical
      potential of the venom components.

PMID- 25603281
TI  - Recent insights into Groucho co-repressor recruitment and function.
AB  - Gene expression is often controlled by transcriptional repressors during
      development. Many transcription factors lack intrinsic repressive activity but
      recruit co-factors that inhibit productive transcription. Here we discuss new
      insights and models for repression mediated by the Groucho/Transducin-Like
      Enhancer of split (Gro/TLE) family of co-repressor proteins. 

PMID- 25603282
TI  - Mismatch negativity indices of enhanced preattentive automatic processing in
      panic disorder as measured by a multi-feature paradigm.
AB  - Panic disorder (PD) is a mental disorder characterized by recurrent panic attacks
      and worrying about having subsequent attacks. Mismatch negativity (MMN) has been
      established as a correlate of preattentive automatic processing. The aim of the
      present study is to investigate the preattentive automatic information processing
      in PD patients as measured by MMN. Subjects included 15 medication-free patients
      with a DSM-IV diagnosis of PD and 15 age-matched healthy volunteers. MMN was
      investigated using event-related potentials. The protocol used a multi-feature
      paradigm. Mean amplitudes and peak latencies were subjected to repeated-measures
      ANOVAs. PD patients showed a significantly increased MMN of sound intensity and
      location compared with healthy participants. The correlation between the
      amplitudes of intensity-MMN and disease severity was also significant. These data
      provide evidence of anomalous preattentive automatic information processing in PD
      patients. In particular, the abnormality may be specific for PD. 

PMID- 25603283
TI  - Equivalent mismatch negativity deficits across deviant types in early illness
      schizophrenia-spectrum patients.
AB  - Neurophysiological abnormalities in auditory deviance processing, as reflected by
      the mismatch negativity (MMN), have been observed across the course of
      schizophrenia. Studies in early schizophrenia patients have typically shown
      varying degrees of MMN amplitude reduction for different deviant types,
      suggesting that different auditory deviants are uniquely processed and may be
      differentially affected by duration of illness. To explore this further, we
      examined the MMN response to 4 auditory deviants (duration, frequency,
      duration+frequency "double deviant", and intensity) in 24 schizophrenia-spectrum
      patients early in the illness (ESZ) and 21 healthy controls. ESZ showed
      significantly reduced MMN relative to healthy controls for all deviant types
      (p<0.05), with no significant interaction with deviant type. No correlations with
      clinical symptoms were present (all ps>0.05). These findings support the
      conclusion that neurophysiological mechanisms underlying processing of auditory
      deviants are compromised early in illness, and these deficiencies are not
      specific to the type of deviant presented. 

PMID- 25603285
TI  - Enriched Intestinal Stem Cell Seeding Improves the Architecture of Tissue
      Engineered Intestine.
AB  - OBJECTIVE: To develop a methodology to separate intestinal stem cell (ISC)
      enriched crypts from differentiated epithelial cell (DEC)-containing villi to
      improve the morphology of tissue-engineered intestine (TEI). METHODS: Small
      intestinal tissues from 5- to 7-day-old transgenic Lgr5-EGFP mice (with
      fluorescently labeled ISCs) were used to measure the height of villi and the
      depth of crypts. Based on the significant size difference between crypts and
      villi, a novel cell filtration system was developed. Filtration of mixed organoid
      units from full-thickness intestine of transgenic Lgr5-EGFP mice allowed
      determination of the percentage of ISCs in the different size-based filtration
      fractions obtained. In vivo, 5-7-day-old Lewis rat pups were used as cell donors
      to obtain purified crypts and villi, and the dams of the pups served as
      recipients. Flat and tubular polyglycolic acid (PGA) scaffolds were seeded with
      either ISC-enriched crypts or DEC-containing villi and implanted intra
      abdominally on the anterior abdominal wall. After 1, 3, 7, 14, 21, and 28 days of
      in vivo incubation, explants were processed for histologic evaluation. RESULTS:
      Small intestine from transgenic Lgr5-EGFP mice contained villi with an average
      height of 134.89+/-41.91 MUm and crypts with an average depth of 49.59+/-8.95
      MUm. After filtration, we found that the 100-200 MUm fractions contained
      relatively pure villi in which DECs were located, whereas the 25-70 MUm range
      fractions contained concentrated crypts in which ISCs were located. In vivo, flat
      PGA scaffolds implanted with purified crypts formed well-developed mucosa by day
      14 postimplantation, whereas flat scaffolds seeded with villi were replaced with
      fibrous tissue. Tubular scaffolds seeded with the crypt fraction developed a well
      formed mucosal layer on the interior surface, with 80.9% circumferential mucosal
      engraftment and an average villous height of 478+/-65 MUm, which was very close
      to native intestine (512+/-98 MUm), whereas tubular scaffolds seeded with the
      villous fraction only had 21.7% circumferential mucosal engraftment and an
      average villous height of 243+/-78 MUm. CONCLUSION: The novel filtration system
      described can effectively and efficiently isolate ISC-containing crypts. TEI
      produced from ISC-containing crypts has an improved morphology that is similar to
      native intestine.

PMID- 25603284
TI  - Allostatic dysregulation of natural reward processing in prescription opioid
      misuse: autonomic and attentional evidence.
AB  - Chronic pain patients who misuse prescription opioids may suffer from allostatic
      dysregulation of natural reward processing. Hence, this study examined whether
      prescription opioid misusers with chronic pain (n=72) evidenced decreased natural
      reward responsiveness relative to non-misusers with chronic pain (n=26). Subjects
      completed a dot probe task containing pain-related, opioid-related, and natural
      reward stimuli while attentional bias (AB) scores and heart rate variability
      (HRV) responses were assessed. Compared to non-misusers, misusers evidenced
      significantly more attenuated HRV responses to opioid, pain, and natural reward
      cues presented during the dot probe task. These significant between-groups
      differences in HRV were largest during attention to natural reward cues, but
      became non-significant in a sensitivity analysis controlling for opioid dosing.
      In addition, non-misusers evidenced an AB toward natural reward cues, whereas
      misusers did not. Findings suggest that opioid misusers exhibit attentional and
      autonomic deficits during reward processing. 

PMID- 25603286
TI  - (Dis)similar Analogues of Riboswitch Metabolites as Antibacterial Lead Compounds.
AB  - The rise of antimicrobial resistance in human pathogenic bacteria has increased
      the necessity for the discovery of novel, yet unexplored antibacterial drug
      targets. Riboswitches, which are embedded in untranslated regions of bacterial
      messenger RNA (mRNA), represent such an interesting target structure. These RNA
      elements regulate gene expression upon binding to natural metabolites, second
      messengers, and inorganic ions, such as fluoride with high affinity and in a
      highly discriminative manner. Recently, efforts have been directed toward the
      identification of artificial riboswitch activators by establishing high
      throughput screening assays, fragment-based screening, and structure-guided
      ligand design approaches. Emphasis in this review is placed on the special
      requirements and synthesis of new potential antibiotic drugs that target
      riboswitches in which dissimilarity is an important aspect in the design of
      potential lead compounds. 

PMID- 25603287
TI  - Stereospecific phosphorylation by the central mitotic kinase Cdk1-cyclin B.
AB  - The cis vs trans conformation, or shape, of phosphoserine-proline (pSer-Pro), a
      prevalent motif in cell cycle proteins, may play a significant role in regulating
      mitosis. We demonstrate that Cdk1-cyclin B, the central mitotic kinase, is
      specific for the trans conformation, not cis, of synthetic, locked Ser-Pro 11
      residue peptide substrates, using LC-MSMS detection and sequencing of
      phosphorylated products. This substrate stereospecificity may contribute an
      additional level of mitotic regulation. 

PMID- 25603288
TI  - Evaluation of the potential of anoxic biodegradation of intracellular and
      dissolved microcystins in lake sediments.
AB  - The kinetics of the anoxic biodegradation of intracellular and dissolved
      microcystin (MCs) and the effects of soluble organic materials on the process
      were investigated via a series of well-controlled microcosm experiments. The
      potential for the removal of intracellular and dissolved MCs from lake sediment
      differed. The dissolved MCs could be degraded to below the detection limit at 20 
      degrees C within one to 3 days after a lag phase of 2-6 days under anoxic
      conditions. The levels of intracellular MCs were also significantly reduced in
      the sun-dried cyanobacterial samples but not rapidly reduced in fresh
      cyanobacterial samples until the cells were ruptured. The addition of soluble
      organic matter enhanced the anoxic biodegradation of MCs. These results indicate
      that the application of anoxic biodegradation via lake sediments is an effective
      method to remove dissolved and intracellular MCs and that this process exhibits
      significant bioremediation potential for the further treatment of cyanobacteria.

PMID- 25603289
TI  - Extraction of molybdenum and vanadium from the spent diesel exhaust catalyst by
      ammonia leaching method.
AB  - Molybdenum (Mo) and vanadium (V) were effectively extracted from the spent diesel
      exhaust catalyst (V2O5-MoO3/TiO2) by using an ammonia leaching method. Meanwhile,
      the structure of the spent catalyst carrier (TiO2) was not destroyed and might be
      reused. The effects of ammonia (NH3 . H2O) concentration, leaching temperature
      and time, concentration of hydrogen peroxide (H2O2) and liquid to solid ratio on
      the extraction of Mo and V were systematically investigated. It is shown that the
      extraction efficiency of Mo increased from 68.68% to 96.45% while the extraction
      efficiency of V remained stable at 27% with increasing ammonia concentration from
      2.95 to 7.38 mol/L, leaching temperature from 298.15 to 473.15K, and reaction
      time from 1 to 8h. With the concentration of H2O2 solution increasing from 1.0 to
      2.5 mol/L, the extraction efficiency of V increased from 26.87% to 39.73%. Under
      the optimum conditions (the ammonia concentration of 4.5 mol/L, leaching
      temperature of 413.15K, reaction time of 2h, the H2O2 solution concentration of
      1.0 mol/L and the liquid to solid ratio of 20/1 mL/g), the extraction
      efficiencies of Mo and V reached 95.13% and 46.25%. Moreover, the catalyst
      carrier TiO2 with anatase crystal phase was also obtained.

PMID- 25603290
TI  - Topological study on the toxicity of ionic liquids on Vibrio fischeri by the
      quantitative structure-activity relationship method.
AB  - As environmentally friendly solvents, ionic liquids (ILs) are unlikely to act as
      air contaminants or inhalation toxins resulting from their negligible vapor
      pressure and excellent thermal stability. However, they can be potential water
      contaminants because of their considerable solubility in water; therefore, a
      proper toxicological assessment of ILs is essential. The environmental fate of
      ILs is studied by quantitative structure-activity relationship (QSAR) method. A
      multiple linear regression (MLR) model is obtained by topological method using
      toxicity data of 157 ILs on Vibrio fischeri, which are composed of 74 cations and
      22 anions. The topological index developed in our research group is used for
      predicting the V. fischeri toxicity for the first time. The MLR model is precise
      for estimating LogEC50 of ILs on V. fischeri with square of correlation
      coefficient (R(2)) = 0.908 and the average absolute error (AAE) = 0.278.

PMID- 25603291
TI  - Organics and nitrogen removal from textile auxiliaries wastewater with A2O-MBR in
      a pilot-scale.
AB  - The removal of organic compounds and nitrogen in an anaerobic-anoxic-aerobic
      membrane bioreactor process (A(2)O-MBR) for treatment of textile auxiliaries (TA)
      wastewater was investigated. The results show that the average effluent
      concentrations of chemical oxygen demand (COD), ammonium nitrogen (NH4(+)-N) and
      total nitrogen (TN) were about 119, 3 and 48 mg/L under an internal recycle ratio
      of 1.5. The average removal efficiency of COD, NH4(+)-N and TN were 87%, 96% and
      55%, respectively. Gas chromatograph-mass spectrometer analysis indicated that,
      although as much as 121 different types of organic compounds were present in the
      TA wastewater, only 20 kinds of refractory organic compounds were found in the
      MBR effluent, which could be used as indicators of effluents from this kind of
      industrial wastewater. Scanning electron microscopy analysis revealed that
      bacterial foulants were significant contributors to membrane fouling. An
      examination of foulants components by wavelength dispersive X-ray fluorescence
      showed that the combination of organic foulants and inorganic compounds enhanced
      the formation of gel layer and thus caused membrane fouling. The results will
      provide valuable information for optimizing the design and operation of
      wastewater treatment system in the textile industry.

PMID- 25603292
TI  - Impact of S fertilizers on pore-water Cu dynamics and transformation in a
      contaminated paddy soil with various flooding periods.
AB  - Impact of S fertilization on Cu mobility and transformation in contaminated paddy
      soils has been little reported. In this study, we investigated the dynamics and
      transformation of dissolved and colloidal Cu in the pore water of a contaminated
      paddy soil after applying ammonium sulphate (AS) and sulfur coated urea (SCU)
      with various flooding periods (1, 7 and 60 days). Compared to the control soil,
      the AS-treated soil released more colloidal and dissolved Cu over the entire
      flooding period, while the SCU-treated soil had lower colloidal Cu after 7-day
      flooding but higher colloidal and dissolved Cu after 60-day flooding. Microscopic
      X-ray fluorescence (MU-XRF) analysis found a close relationship between Fe and Cu
      distribution on soil colloids after 60-day flooding, implying the formation of
      colloidal Fe/Cu sulphide coprecipitates. Cu K-edge X-ray absorption near-edge
      structure (XANES) spectroscopy directly revealed the transformation of outer
      sphere complexed Cu(II) species to Cu(II) sulphide and reduced Cu2O in the
      colloids of S-treated soils after 60-day flooding. These results demonstrated the
      great influence of S fertilization on pore-water Cu mobility by forming Cu
      sulphide under flooding conditions, which facilitated our understanding and
      control of Cu loss in contaminated paddy soils under S fertilization. 

PMID- 25603293
TI  - Growth inhibition and effect on photosystem by three imidazolium chloride ionic
      liquids in rice seedlings.
AB  - The effects of three imidazolium chloride ionic liquids (ILs) including 1-octyl-3
      methylimidazolium chloride ionic liquid ([OMIM]Cl), 1-decyl-3-methylimidazolium
      chloride ionic liquid ([DMIM]Cl) and 1-dodecyl-3-methylimidazolium chloride ionic
      liquid ([C12MIM]Cl) were studied in hydroponically grown rice seedlings. The
      growth inhibition rate increased and the Hill reaction activity of isolated rice
      chloroplasts decreased with increasing ILs concentrations. The IC50,5d for stem
      length was 0.70 mg/L of [OMIM]Cl, 0.15 mg/L of [DMIM]Cl, and 0.055 mg/L of
      [C12MIM]Cl, respectively. The SOD, POD and CAT activities of chloroplast
      exhibited initial increases followed by decreases in activity with increasing ILs
      concentrations. Chlorophyll fluorescence parameters such as the maximum effective
      quantum yield of PSII(Fv/Fm), the potential activity of PSII(Fv/F0), the yield of
      photochemical quantum [Y(II)], the photochemical quenching coefficient (qP), the
      non-photochemical quenching coefficient (NPQ) and the relative electron transport
      ratio (rETR) were affected, showing that ILs will damage the PSII. The results
      demonstrated that imidazolium chloride ILs are phytotoxic to rice growth and
      their photosystem, the toxicity increased as the alkyl chain length increased
      with the following order: [OMIM]Cl<[DMIM]Cl<[C12MIM]Cl. The results will help to
      better understand the possible role of the defense mechanism in rice caused by
      ILs exposure.

PMID- 25603295
TI  - Exploring bacterial community structure and function associated with atrazine
      biodegradation in repeatedly treated soils.
AB  - Substantial application of the herbicide atrazine in agriculture leads to
      persistent contamination, which may damage the succeeding crops and pose
      potential threats to soil ecology and environmental health. Here, the degradation
      characteristics of atrazine and dynamic change of soil bacterial community
      structure and function as well as their relations were studied during three
      repeated treatments at the recommended, double, and five-fold doses. The results
      showed that the degradation half-life of atrazine obviously decreased with
      increased treatment frequency. Soil microbial functional diversity displayed a
      variation trend of suppression-recovery-stimulation, which was associated with
      increased degradation rate of atrazine. 16S amplicon sequencing was conducted to
      explore bacterial community structure and correlate the genus to potential
      atrazine degradation. A total of seven potentially atrazine-degrading bacterial
      genera were found including Nocardioides, Arthrobacter, Bradyrhizobium,
      Burkholderia, Methylobacterium, Mycobacterium, and Clostridium. These bacterial
      genera showed almost complete atrazine degradation pathways including
      dechlorination, dealkylation, hydroxylation, and ring cleavage. Furthermore, the
      relative abundance of four of them (i.e., Nocardioides, Arthrobacter,
      Methylobacterium, and Bradyrhizobium) increased with treatment frequency and
      atrazine concentration, suggesting that they may participate in atrazine
      degradation during repeated treatments. Our findings reveal the potential
      relationship between atrazine degradation and soil bacterial community structure
      in repeatedly treated soils. 

PMID- 25603294
TI  - Facile hydrothermal preparation of recyclable S-doped graphene sponge for Cu2+
      adsorption.
AB  - Graphene sponge (GS) has been widely employed for water purification, but
      adsorption capacity loss frequently occurs during the formation of spongy
      structure. In this study, we reported the hydrothermal preparation of S-doped GS
      for the removal of Cu(2+) with a huge adsorption capacity of 228 mg/g, 40 times
      higher than that of active carbon. The adsorption isotherm could be well fitted
      into the Freundlich model with a KF value of 36.309(L/mg)(1/n). The equilibrium
      adsorption could be fully achieved in the first 5 min. In the thermodynamics
      study, the negative DeltaG indicated that the adsorption was spontaneous and
      physisorption in nature. The positive DeltaH implied that the adsorption was
      endothermic. The changes of both pH and ionic strength had no apparent influence
      on the adsorption. S-doped GS could be easily regenerated by washing with acidic
      thiourea. Moreover, S-doped GS could be used for the adsorption of other heavy
      metal ions, too. The implication to the applications of S-doped GS in water
      treatment is discussed.

PMID- 25603296
TI  - Removal of trace Cd2+ from aqueous solution by foam fractionation.
AB  - In recent years, aqueous foam was known as an efficient technique with high
      potential on being used to remove heavy metal ions from the polluted water, not
      only because of the low cost, simple operation, but also ascribed to the high
      removal efficiency of trace heavy metal ions and would not cause secondary
      pollution to the environment. In this paper, the removal of Cd(2+) from aqueous
      solution by aqueous foam stabilized by a kind of novel anionic-nonionic
      surfactant sodium trideceth-4 carboxylate (AEC) was investigated. The effect of
      conditions such as surfactant/metal ions molar ratio, surfactant concentration on
      the removal efficiency was studied. In large concentration range of surfactant,
      the removal rate was higher than 90%, and could reach up to 99.8% under the
      optimum conditions. The Zeta potential of gas bubbles in the AEC solutions was
      determined to verify the combination between the negative charged group heads of
      surfactant molecules and heavy metal ions, and isothermal titration calorimeter
      (ITC) determination was utilized to demonstrate the interaction, which helped to
      understand the mechanisms more clearly. 

PMID- 25603297
TI  - PM2.5 acidity at a background site in the Pearl River Delta region in fall-winter
      of 2007-2012.
AB  - Based on field observations and thermodynamic model simulation, the annual trend
      of PM2.5 acidity and its characteristics on non-hazy and hazy days in fall-winter
      of 2007-2012 in the Pearl River Delta region were investigated. Total acidity
      ([H(+)](total)) and in-situ acidity ([H(+)](in-situ)) of PM2.5 significantly
      decreased (F-test, p < 0.05) at a rate of -32 +/- 1.5 nmol m(-3)year(-1) and -9
      +/- 1.7 nmol m(-3) year(-1), respectively. The variation of acidity was mainly
      caused by the change of the PM2.5 component, i.e., the decreasing rates of
      [H(+)](total) and [H(+)](in-situ) due to the decrease of sulfate (SO4(2-))
      exceeded the increasing rate caused by the growth of nitrate (NO3(-)).
      [H(+)](total), [H(+)](in-situ) and liquid water content on hazy days were 0.9
      2.2, 1.2-3.5 and 2.0-3.0 times those on non-hazy days, respectively. On hazy
      days, the concentration of organic matter (OM) showed significant enhancement
      when [H(+)](in-situ) increased (t-test, p < 0.05), while this was not observed on
      non-hazy days. Moreover, when the acidity was low (i.e., R = [NH4(+)]/(2 * [SO4(2
      )]+[NO3(-)])>0.6), NH4NO3 was most likely formed via homogenous reaction. When
      the acidity was high (R <= 0.6), the gas-phase formation of NH4NO3 was inhibited,
      and the proportion of NO3(-) produced via heterogeneous reaction of N2O5 became
      significant.

PMID- 25603298
TI  - Combination of cathodic reduction with adsorption for accelerated removal of
      Cr(VI) through reticulated vitreous carbon electrodes modified with sulfuric acid
      glycine co-doped polyaniline.
AB  - Improving the reduction kinetics is crucial in the electroreduction process of
      Cr(VI). In this study, we developed a novel adsorption-electroreduction system
      for accelerated removal of Cr(VI) by employing reticulated vitreous carbon
      electrode modified with sulfuric acid-glycine co-doped polyaniline (RVC/PANI-SA
      GLY). Firstly, response surface methodology confirmed the optimum polymerization
      condition of co-doped polyaniline for modifying electrodes (Aniline, sulfuric
      acid and glycine, respectively, of 0.2 mol/L, 0.85 mol/L, 0.93 mol/L) when
      untraditional dopant glycine was added. Subsequently, RVC/PANI-SA-GLY showed
      higher Cr(VI) removal percentages in electroreduction experiments over RVC
      electrode modified with sulfuric acid doped polyaniline (RVC/PANI-SA) and bare
      RVC electrode. In contrast to RVC/PANI-SA, the improvement by RVC/PANI-SA-GLY was
      more significant and especially obvious at more negative potential, lower initial
      Cr(VI) concentration, relatively less acidic solution and higher current
      densities, best achieving 7.84% higher removal efficiency with entire Cr(VI)
      eliminated after 900 s. Current efficiencies were likewise enhanced by RVC/PANI
      SA-GLY under quite negative potentials. Fourier transform infrared (FTIR) and
      energy dispersive spectrometer (EDS) analysis revealed a possible adsorption
      reduction mechanism of RVC/PANI-SA-GLY, which greatly contributed to the faster
      reduction kinetics and was probably relative to the absorption between protonated
      amine groups of glycine and HCrO4(-). Eventually, the stability of RVC/PANI-SA
      GLY was proven relatively satisfactory.

PMID- 25603299
TI  - Time-dependent performance of soil mix technology stabilized/solidified
      contaminated site soils.
AB  - This paper presents the strength and leaching performance of
      stabilized/solidified organic and inorganic contaminated site soil as a function
      of time and the effectiveness of modified clays applied in this project. Field
      trials of deep soil mixing application of stabilization/solidification (S/S) were
      performed at a site in Castleford in 2011. A number of binders and addictives
      were applied in this project including Portland cement (PC), ground granulated
      blastfurnace slag (GGBS), pulverised fuel ash (PFA), MgO and modified clays.
      Field trial samples were subjected to unconfined compressive strength (UCS), BS
      CN 12457 batch leaching test and the extraction of total organics at 28 days and
      1.5 years after treatment. The results of UCS test show that the average strength
      values of mixes increased from 0-3250 kPa at 28 days to 250-4250 kPa at 1.5 years
      curing time. The BS EN 12457 leachate concentrations of all metals were well
      below their drinking water standard, except Ni in some mixes exceed its drinking
      water standard at 0.02 mg/l, suggesting that due to varied nature of binders, not
      all of them have the same efficiency in treating contaminated soil. The average
      leachate concentrations of total organics were in the range of 20-160 mg/l at 28
      days after treatment and reduced to 18-140 mg/l at 1.5 years. In addition, organo
      clay (OC)/inorgano-organo clay (IOC) slurries used in this field trial were found
      to have a negative effect on the strength development, but were very effective in
      immobilizing heavy metals. The study also illustrates that the surfactants used
      to modify bentonite in this field trail were not suitable for the major organic
      pollutants exist in the site soil in this project.

PMID- 25603300
TI  - Fabrication and characterization of PbO2 electrode modified with [Fe(CN)6](3-)
      and its application on electrochemical degradation of alkali lignin.
AB  - PbO2 electrode modified by [Fe(CN)6](3-) (marked as FeCN-PbO2) was prepared by
      electro-deposition method and used for the electrochemical degradation of alkali
      lignin (AL). The surface morphology and the structure of the electrodes were
      characterized by scanning electronic microscopy (SEM) and X-ray diffraction
      (XRD), respectively. The stability and electrochemical activity of FeCN-PbO2
      electrode were characterized by accelerated life test, linear sweep voltammetry,
      electrochemical impedance spectrum (EIS) and AL degradation. The results showed
      that [Fe(CN)6](3-) increased the average grain size of PbO2 and formed a compact
      surface coating. The service lifetime of FeCN-PbO2 electrode was 287.25 h, which
      was longer than that of the unmodified PbO2 electrode (100.5h). The FeCN-PbO2
      electrode showed higher active surface area and higher oxygen evolution potential
      than that of the unmodified PbO2 electrode. In electrochemical degradation tests,
      the apparent kinetics coefficient of FeCN-PbO2 electrode was 0.00609 min(-1),
      which was higher than that of unmodified PbO2 electrode (0.00419 min(-1)). The
      effects of experimental parameters, such as applied current density, initial AL
      concentration, initial pH value and solution temperature, on electrochemical
      degradation of AL by FeCN-PbO2 electrode were evaluated.

PMID- 25603301
TI  - Removal of sulfuric acid mist from lead-acid battery plants by coal fly ash-based
      sorbents.
AB  - Sorbents from coal fly ash (CFA) activated by NaOH, CaO and H2O were prepared for
      H2SO4 mist removal from lead-acid battery plants. The effects of parameters
      including temperature, time, the ratios of CFA/activator and water/solid during
      sorbent preparation were investigated. It is found that the synthesized sorbents
      exhibit much higher removal capacity for H2SO4 mist when compared with that of
      raw coal fly ash and CaO except for H2O activated sorbent and this sorbent was
      hence excluded from the study because of its low capacity. The H2SO4 mist removal
      efficiency increases with the increasing of preparation time length and
      temperature. In addition, the ratios of CFA/activator and water/solid also impact
      the removal efficiency, and the optimum preparation conditions are identified as:
      a water/solid ratio of 10:1 at 120  degrees C for 10h, a CFA:CaO weight ratio of
      10:1, and a NaOH solution concentration of 3 mol/L. The formation of rough
      surface structure and an increased surface area after NaOH/CaO activation favor
      the sorption of H2SO4 mist and possible sorption mechanisms might be
      electrostatic attractions and chemical precipitation between the surface of
      sorbents and H2SO4 mist.

PMID- 25603302
TI  - Absolute quantification of norovirus capsid protein in food, water, and soil
      using synthetic peptides with electrospray and MALDI mass spectrometry.
AB  - Norovirus infections are one of the most prominent public health problems of
      microbial origin in the U.S. and other industrialized countries. Surveillance is
      necessary to prevent secondary infection, confirm successful cleanup after
      outbreaks, and track the causative agent. Quantitative mass spectrometry, based
      on absolute quantitation with stable-isotope labeled peptides, is a promising
      tool for norovirus monitoring because of its speed, sensitivity, and robustness
      in the face of environmental inhibitors. In the current study, we present two new
      methods for the detection of the norovirus genogroup I capsid protein using
      electrospray and matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry. The peptide TLDPIEVPLEDVR was used to quantify norovirus-like
      particles down to 500 attomoles with electrospray and 100 attomoles with MALDI.
      With MALDI, we also demonstrate a detection limit of 1 femtomole and a
      quantitative dynamic range of 5 orders of magnitude in the presence of an
      environmental matrix effect. Due to the rapid processing time and applicability
      to a wide range of environmental sample types (bacterial lysate, produce, milk,
      soil, and groundwater), mass spectrometry-based absolute quantitation has a
      strong potential for use in public health and environmental sciences. 

PMID- 25603304
TI  - Stress assessment in small ruminants kept on city farms in southern Germany.
AB  - Sheep and goats are frequently used in nonhuman animal-assisted activities on
      city farms. There are few data available on this type of usage of small
      ruminants. Health evaluations, behavioral observations (feeding, resting,
      comfort, explorative and social behaviors), behavioral tests (human approach
      tests and touch test), and measurements of fecal cortisol metabolites and heart
      rate were performed to assess stress levels in 25 sheep and 32 goats on 7 city
      farms and 2 activity playgrounds in Germany. No evidence was found that the
      animals suffered from major distress. Health evaluations, behavioral
      observations, and behavioral tests proved to be the methods of stress assessment
      most suitable for routine on-farm checks in these settings.

PMID- 25603305
TI  - Ossifying fibromyxoid tumor (OFMT) - A rare cause of a painful thumb.
AB  - INTRODUCTION: Ossifying fibromyxoid tumor (OFMT) is an uncommon soft tissue and
      bone neoplasm with just over 100 cases being reported in the literature. They
      present as small, slow-growing asymptomatic subcutaneous nodules in the soft
      tissues of the trunk and extremities. PRESENTATION OF CASE: We present a case of
      a 25-year-old, right hand dominant gentleman who complained of a seven-year
      history of pain and discomfort in the dorsal aspect of the right thumb. He was
      unable to move his interphalangeal joint (IPJ) but had good function otherwise.
      Examination revealed a localized tender swelling over the dorsal aspect of the
      IPJ. The thumb was fixed in extension. X-ray revealed marked abnormal soft tissue
      swelling around the interphalangeal joint, cystic abnormalities and new bone
      formation. Biopsy showed fibrous tissue containing nodules of tumor with cells in
      a myxoid background, rounded and histiocytoid to elongated and spindle shaped.
      CD57, type IV collagen, smooth muscle actin were found and CD56 and EMA were
      focally positive. These were in keeping with ossifying fibromyxoid tumor with an
      atypical immunophenotype. DISCUSSION: The tumor was formally excised with the
      flexor pollicis longus tendon. A two-month review revealed his pain had settled.
      As the tumor had an atypical immunophenotype he was referred to the regional
      sarcoma team. CONCLUSION: OMFT can present with atypical clinical, radiological
      and histological features. It is managed in a multidisciplinary setting and often
      requires lifetime follow up to detect a recurrence given the uncertain nature of
      these lesions.

PMID- 25603303
TI  - Influences of gestational obesity on associations between genotypes and gene
      expression levels in offspring following maternal gastrointestinal bypass surgery
      for obesity.
AB  - METHODS: Whole-genome genotyping and gene expression analyses in blood of 22 BMS
      and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5
      Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we
      analyzed interactions between offspring gene variations and maternal surgical
      status on offspring gene expression levels. Altered biological functions and
      pathways were identified and visualized using DAVID and Ingenuity Pathway
      Analysis. RESULTS: Significant interactions (p <= 1.22 x 10(-12)) were found for
      525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved.
      Gene function and pathway analysis demonstrated enrichment of transcription and
      of cellular metabolism functions and overrepresentation of cellular stress and
      signaling, immune response, inflammation, growth, proliferation and development
      pathways. CONCLUSION: We suggest that impaired maternal gestational metabolic
      fitness interacts with offspring gene variations modulating gene expression
      levels, providing potential mechanisms explaining improved cardiometabolic risk
      profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate
      metabolism.

PMID- 25603306
TI  - Recurring spontaneous aseptic pneumoperitoneum presenting secondary to an
      unrelated chief complaint: A case report.
AB  - INTRODUCTION: Pneumoperitoneum, observed by radiography, is typically associated
      with the perforation of hollow viscous. More than 90% of all cases of
      pneumoperitoneum are the result of a gastrointestinal tract perforation. These
      patients usually present with signs of acute peritonitis and require immediate
      surgical exploration and intervention. However, rare cases of idiopathic
      spontaneous pneumoperitoneum do occur without any indication of visceral
      perforation and other known causes of the free intraperitoneal gas. PRESENTATION
      OF CASE: A 66-year-old male presented to the emergency department on three
      separate occasions with similar episodes six months apart. Upon physical
      examination and subsequent testing, chest radiography revealed the presence of
      free intraperitoneal gas. A computerized tomography (CT) was performed in which
      pneumatosis and pneumoperitoneum was reported with the first two admissions and
      both laparotomies were negative. This patient continues to be followed for
      prostate cancer and bony metastases. All subsequent CT scans (last performed
      01/2014) have shown no acute or chronic abdominal pathology and no obstructions.
      He also had upper and lower endoscopies in 2011, which were negative. DISCUSSION:
      This case revealed very different finding than anticipated. The patient presented
      to the emergency department with symptoms unrelated to the CT findings of free
      intraperitoneal gas. On two separate occasions, the patient underwent a
      laparotomy with negative findings. The conventional course of treatment for
      pneumoperitoneum was followed, but was it necessary? Though the presentation of
      pneumoperitoneum is most often associated with significant pathology requiring
      surgical intervention, a more conservative approach may be applicable in cases
      similar to the one presented here.

PMID- 25603307
TI  - Spontaneous regression of Merkel cell carcinoma: A case report and review of the
      literature.
AB  - INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and highly aggressive primary
      cutaneous neuroendocrine carcinoma, most often occurring in the elderly.
      Recurrence is frequent and in 40% of cases regional and distant metastases
      develop. Despite this, there have been reports of spontaneous regression. We
      report the first case of MCC with primary complete spontaneous regression of the
      nose in an 86-year-old woman following an incisional biopsy. PRESENTATION OF
      CASE: An 86-year-old woman presented with a violaceous lump on the left side of
      the nose measuring 25*25mm. Incisional biopsy of the lesion showed MCC and
      immunohistochemistry confirmed diagnosis. Following an 8-week period the lesion
      completely disappeared and histology did not show any residual MCC but
      immunohistochemistry demonstrated a mixture of T and B cells. DISCUSSION:
      Complete spontaneous regression (CSR) is rare. The literature documents 22
      similar cases of CSR of MCC. From this case report and previous literature the
      most likely reason for regression is a T-cell mediated immune response.
      CONCLUSION: To the best of our knowledge, this is the first described case of MCC
      with primary CSR of the nose. Exact mechanism of regression remains unclear.
      Further research is needed in identifying pathway of immune response and possible
      immunotherapy as a cure.

PMID- 25603308
TI  - Predictors of follow-up for overweight youth and parents.
AB  - Attrition is a significant problem for health care providers working with youth
      and parents involved in childhood obesity treatment. Barriers for families in
      childhood obesity treatment have been explored, but less is known about factors
      that may be associated with follow-up attendance. The purpose of this study is to
      explore youth and parent variables, pediatrician's evaluations of youth and
      parents' likelihood to change (LTC), and their association with attendance at
      follow-up. One hundred ninety-three youth and parent dyads were included in the
      sample; slightly more than half of the sample did not return for a follow up
      visit. Descriptive statistics, paired and independent t tests, and correlations
      were used to determine associations between youth and parent demographic factors,
      attendance at follow-up, and pediatricians' evaluation of likelihood to change.
      Evaluations of LTC and demographic factors did not significantly associate with
      follow-up appointment attendance. Single parents were more likely to be rated by
      pediatricians as likely to make changes. Implications for future research and
      clinical practice are discussed.

PMID- 25603309
TI  - The Q-List manifesto: how to get things right in generalist medical practice.
AB  - Checklists have become popular in medical practice since the publication of
      surgeon Atul Gawande's book, The Checklist Manifesto: How to Get Things Right.
      Based on his 26 years of practice as a family physician and informed by scholarly
      works from other professional disciplines, the author suggests that although
      checklists are helpful for promoting habitual reflection, they are limited in
      scope and meaning, and more suited for procedural undertakings than the bio
      psycho-social-existential orientation of generalist practice. The author reviews
      the characteristics of generalist practice and suggests that clinicians develop a
      list of questions to help them recall and examine concepts key to the exploration
      and management of routine and challenging situations with patients. He proposes
      his own Question-List, or Q-List, and recommends its adaptation for use as a
      manifesto to the rich and engaging work of generalist medicine.

PMID- 25603310
TI  - Diabetes knowledge in young adults: associations with hemoglobin A1C.
AB  - The purpose of this study was to quantify associations between hemoglobin A1C
      (A1C) and diabetes knowledge score using an assessment tool developed to evaluate
      the level of diabetes knowledge in young adults with Type 1 diabetes (T1DM) and
      their parent/primary caregiver. Seventy-five participants with T1DM, ages 15-22
      years, completed questionnaires. Two 25-item questionnaires were developed: one
      for patient and one for caregiver. Linear regression quantified associations
      between correct items on the tools and participant A1C and demographic
      characteristics. Mean age of participants was 16.7 +/- 1.7 years, diabetes
      duration 5.9 +/- 4.2 years, 46.7% male, 74.7% Caucasian, 69.3% on multiple daily
      injections, and 30.7% on continuous subcutaneous insulin infusion therapy; 78.7%
      of parents/caregivers completed the questionnaire. A significant interaction was
      observed between patient and caregiver scores with A1C by diabetes duration.
      Among patients with diabetes <6 years, higher patient and caregiver scores were
      associated with lower A1C (-0.25 +/- 0.11, p = .03 and -0.59 +/- 0.19, p = .005,
      respectively) accounting for age, gender, race, therapy, and insurance. Neither
      patient nor caregiver score was associated with A1C in patients with diabetes
      duration >=6 years. Better performance on a diabetes knowledge assessment (for
      both patient and the caregiver) was found to be associated with more favorable
      levels of glycemic control among young adults with diabetes <6 years. Additional
      evaluation of these questionnaires and novel interventions to enhance knowledge
      in this population are needed.

PMID- 25603311
TI  - Ion diffusion coefficients model and molar conductivities of ionic salts in
      aprotic solvents.
AB  - In the study of the electric properties of electrolytes, the determination of the
      diffusion coefficients of the species that intervene in the charge transport
      process is of great importance, particularly that of the free ions (D(+) and D(
      )), the only species that contribute to the conductivity. In this work we propose
      a model that allows, with reasonable assumptions, determination of D(+) and D(-),
      and the degree of dissociation of the salt, alpha, at different concentrations,
      using the diffusion coefficients experimentally obtained with NMR. Also, it is
      shown that the NMR data suffice to estimate the conductivity of the electrolytes.
      The model was checked by means of experimental results of conductivity and NMR
      diffusion coefficients obtained with solutions of lithium triflate in ethylene
      and propylene carbonates, as well as with other results taken from the
      literature. 

PMID- 25603312
TI  - A 3D numerical study of the collateral capacity of the Circle of Willis with
      anatomical variation in the posterior circulation.
AB  - BACKGROUND: The Circle of Willis (CoW) is the most important collateral pathway
      of the cerebral artery. The present study aims to investigate the collateral
      capacity of CoW with anatomical variation when unilateral internalcarotid artery
      (ICA) is occluded. METHODS: Basing on MRI data, we have reconstructed eight 3D
      models with variations in the posterior circulation of the CoW and set four
      different degrees of stenosis in the right ICA, namely 24%, 43%, 64% and 79%,
      respectively. Finally, a total of 40 models are performed with computational
      fluid dynamics simulations. All of the simulations share the same boundary
      condition with static pressure and the volume flow rate (VFR) are obtained to
      evaluate their collateral capacity. RESULTS: As for the middle cerebral artery
      (MCA) and the anterior cerebral artery (ACA), the transitional-type model
      possesses the best collateral capacity. But for the posterior cerebral artery
      (PCA), unilateral stenosis of ICA has the weakest influence on the unilateral
      posterior communicating artery (PCoA) absent model. We also find that the full
      fetal-type posterior circle of Willis is an utmost dangerous variation which must
      be paid more attention. CONCLUSION: The results demonstrate that different models
      have different collateral capacities in coping stenosis of unilateral ICA and
      these differences can be reflected by different outlets. The study could be used
      as a reference for neurosurgeon in choosing the best treatment strategy.

PMID- 25603313
TI  - Synthesis and properties of arylvinylidene-bridged triphenylamines.
AB  - A series of arylvinylidene-bridged triphenylamines were efficiently synthesized
      through the thionation/Barton-Kellogg olefination sequence from their
      corresponding carbonyl precursors. The electrochemical investigations identified
      these highly distorted scaffolds as fairly strong electron donors capable of
      several reversible oxidation steps with the first oxidation occurring at a
      potential comparable to that of ferrocene for the n-hexyl-substituted
      diphenylvinylidene-bridged compound. 

PMID- 25603314
TI  - Variable expression of PIK3R3 and PTEN in Ewing Sarcoma impacts oncogenic
      phenotypes.
AB  - Ewing Sarcoma is an aggressive malignancy of bone and soft tissue affecting
      children and young adults. Ewing Sarcoma is driven by EWS/Ets fusion
      oncoproteins, which cause widespread alterations in gene expression in the cell.
      Dysregulation of receptor tyrosine kinase signaling, particularly involving IGF
      1R, also plays an important role in Ewing Sarcoma pathogenesis. However, the
      basis of this dysregulation, including the relative contribution of EWS/Ets
      dependent and independent mechanisms, is not well understood. In the present
      study, we identify variable expression of two modifiers of PI3K signaling
      activity, PIK3R3 and PTEN, in Ewing Sarcoma, and examine the consequences of this
      on PI3K pathway regulation and oncogenic phenotypes. Our findings indicate that
      PIK3R3 plays a growth-promotional role in Ewing Sarcoma, but suggest that this
      role is not strictly dependent on regulation of PI3K pathway activity. We further
      show that expression of PTEN, a well-established, potent tumor suppressor, is
      lost in a subset of Ewing Sarcomas, and that this loss strongly correlates with
      high baseline PI3K pathway activity in cell lines. In support of functional
      importance of PTEN loss in Ewing Sarcoma, we show that re-introduction of PTEN
      into two different PTEN-negative Ewing Sarcoma cell lines results in
      downregulation of PI3K pathway activity, and sensitization to the IGF-1R small
      molecule inhibitor OSI-906. Our findings also suggest that PTEN levels may
      contribute to sensitivity of Ewing Sarcoma cells to the microtubule inhibitor
      vincristine, a relevant chemotherapeutic agent in this cancer. Our studies thus
      identify PIK3R3 and PTEN as modifiers of oncogenic phenotypes in Ewing Sarcoma,
      with potential clinical implications. 

PMID- 25603315
TI  - Sleep, arousal, and circadian rhythms in adults with obsessive-compulsive
      disorder: a meta-analysis.
AB  - Findings of this meta-analysis show that obsessive-compulsive disorder (OCD) is
      related to disruptions in both the duration and timing of sleep. PsycINFO and
      Google Scholar database searches identified 12 relevant studies that compared
      measures of sleep in individuals with OCD to those of either a healthy control
      group or published norms. Sleep measures included sleep onset latency, sleep
      duration, awakening after sleep onset, percentage of rapid eye movement (REM)
      sleep, percentage of slow wave sleep, and prevalence of delayed sleep phase
      disorder (DSPD). Individual effect sizes were pooled using a random effects
      model. Sleep duration was found to be shorter, and the prevalence of DSPD higher,
      in individuals with OCD compared to controls. Further, excluding samples with
      comorbid depression did not meaningfully reduce the magnitude of these effects
      (although the results were no longer statistically significant) and medication
      use by participants is unlikely to have systematically altered sleep timing.
      Overall, available data suggest that sleep disruption is associated with OCD but
      further research on both sleep duration and sleep timing in individuals with OCD
      is needed. 

PMID- 25603316
TI  - Associative fear learning and perceptual discrimination: a perceptual pathway in
      the development of chronic pain.
AB  - Recent neuropsychological theories emphasize the influence of maladaptive
      learning and memory processes on pain perception. However, the precise
      relationship between these processes as well as the underlying mechanisms remain
      poorly understood; especially the role of perceptual discrimination and its
      modulation by associative fear learning has received little attention so far.
      Experimental work with exteroceptive stimuli consistently points to effects of
      fear learning on perceptual discrimination acuity. In addition, clinical
      observations have revealed that in individuals with chronic pain perceptual
      discrimination is impaired, and that tactile discrimination training reduces
      pain. Based on these findings, we present a theoretical model of which the
      central tenet is that associative fear learning contributes to the development of
      chronic pain through impaired interoceptive and proprioceptive discrimination
      acuity. 

PMID- 25603317
TI  - Unraveling the relationship between trait negative affectivity and habitual
      symptom reporting.
AB  - OBJECTIVE: In two studies, we aimed at further elucidating the relationship
      between trait negative affectivity (NA) and habitual symptom reporting (HSR) by
      relating these variables to measures of executive function, trait questionnaires,
      and effects of emotion induction. METHODS: Healthy female participants (N = 75)
      were selected on their scores for trait NA and for the Checklist for Symptoms in
      Daily Life. Three groups were compared: (1) low NA-low HSR; (2) high NA-low HSR;
      and (3) high NA-high HSR (low NA-high HSR did not occur). In study 1,
      participants underwent a Parametric Go/No-go Task and a Stroop Color-Word test,
      and trait questionnaires measured alexithymia and absorption. Forty-five
      participants (N = 15 in each group) were further engaged in study 2 to induce
      state NA using an affective picture paradigm. RESULTS: Impaired inhibition on the
      Stroop and Go/No go Task characterized high trait NA, but not high HSR, whereas
      alexithymia and absorption were elevated in HSR, regardless of trait NA. Negative
      picture viewing induced elevated state NA in all groups, but only high HSR also
      reported more bodily symptoms. This effect was moderated, but not mediated by
      state NA. CONCLUSION: High trait NA is a vulnerability factor but not a
      sufficient condition to develop HSR. Deficient inhibition is related to the broad
      trait of NA, whereas the moderating effect of state NA on symptom reporting is
      specific for high HSR. Understanding processes related to alexithymia and
      absorption may specifically help to explain elevated HSR.

PMID- 25603318
TI  - Serological responses to Cryptosporidium antigens in inhabitants of Hungary using
      conventionally filtered surface water and riverbank filtered drinking water.
AB  - In this study the putative protective seroprevalence (PPS) of IgG antibodies to
      the 27-kDa and 15/17-kDa Cryptosporidium antigens in sera of healthy participants
      who were and were not exposed to Cryptosporidium oocysts via surface water
      derived drinking water was compared. The participants completed a questionnaire
      regarding risk factors that have been shown to be associated with infection. The
      PPS was significantly greater (49-61%) in settlements where the drinking water
      originated from surface water, than in the control city where riverbank
      filtration was used (21% and 23%). Logistic regression analysis on the risk
      factors showed an association between bathing/swimming in outdoor pools and
      antibody responses to the 15/17-kDa antigen complex. Hence the elevated responses
      were most likely due to the use of contaminated water. Results indicate that
      waterborne Cryptosporidium infections occur more frequently than reported but may
      derive from multiple sources. 

PMID- 25603320
TI  - Are natural resources bad for health?
AB  - The purpose of this paper is to empirically examine whether economic dependence
      on various natural resources is associated with lower investment in health, after
      controlling for countries' geographical and historical fixed effects, corruption,
      autocratic regimes, income levels, and initial health status. Employing panel
      data for 118 countries for the period 1990-2008, we find no compelling evidence
      in support of a negative effect of resources on healthcare spending and outcomes.
      On the contrary, higher dependence on agricultural exports is associated with
      higher healthcare spending, higher life expectancy, and lower diabetes rates.
      Similarly, healthcare spending increases with higher mineral intensity. Finally,
      more hydrocarbon resource rents are associated with less diabetes and obesity
      rates. There is however evidence that public health provision relative to the
      size of the economy declines with greater hydrocarbon resource-intensity; the
      magnitude of this effect is less severe in non-democratic countries.

PMID- 25603321
TI  - Controlled assembly of artificial protein-protein complexes via DNA duplex
      formation.
AB  - DNA-protein conjugates have found a wide range of applications. This study
      demonstrates the formation of defined, non-native protein-protein complexes via
      the site specific labeling of two proteins of interest with complementary strands
      of single-stranded DNA in vitro. This study demonstrates that the affinity of two
      DNA-protein conjugates for one another may be tuned by the use of variable
      lengths of DNA allowing reversible control of complex formation. 

PMID- 25603319
TI  - Human Cerberus prevents nodal-receptor binding, inhibits nodal signaling, and
      suppresses nodal-mediated phenotypes.
AB  - The Transforming Growth Factor-beta (TGFbeta) family ligand Nodal is an essential
      embryonic morphogen that is associated with progression of breast and other
      cancers. It has therefore been suggested that Nodal inhibitors could be used to
      treat breast cancers where Nodal plays a defined role. As secreted antagonists,
      such as Cerberus, tightly regulate Nodal signaling during embryonic development,
      we undertook to produce human Cerberus, characterize its biochemical activities,
      and determine its effect on human breast cancer cells. Using quantitative
      methods, we investigated the mechanism of Nodal signaling, we evaluated binding
      of human Cerberus to Nodal and other TGFbeta family ligands, and we characterized
      the mechanism of Nodal inhibition by Cerberus. Using cancer cell assays, we
      examined the ability of Cerberus to suppress aggressive breast cancer cell
      phenotypes. We found that human Cerberus binds Nodal with high affinity and
      specificity, blocks binding of Nodal to its signaling partners, and inhibits
      Nodal signaling. Moreover, we showed that Cerberus profoundly suppresses
      migration, invasion, and colony forming ability of Nodal expressing and Nodal
      supplemented breast cancer cells. Taken together, our studies provide mechanistic
      insights into Nodal signaling and Nodal inhibition with Cerberus and highlight
      the potential value of Cerberus as anti-Nodal therapeutic. 

PMID- 25603322
TI  - Impact of the structure of biocompatible aliphatic polycarbonates on siRNA
      transfection ability.
AB  - RNAi therapeutics are promising therapeutic tools that have sparked the interest
      of many researchers. In an effort to provide a safe alternative to PEI, we have
      designed a series of new guanidinium- and morpholino-functionalized biocompatible
      and biodegradable polycarbonate vectors. The impact of different functions
      (morpholino-, guanidinium-, hydrophobic groups) of the architecture (linear
      homopolymer to dumbbell-shape) and of the molecular weight of these copolymers on
      their capacity to form polyplexes and to decrease the expression of two
      epigenetic regulators of gene expression, HDAC7 and HDAC5, was evaluated. The use
      of one of these polymers combining morpholine and guanidine functions at the
      ratio >1 and hydrophobic trimethylene carbonate groups showed a significant
      decrease of mRNA and protein level in HeLa cells, similar to PEI. These results
      highlight the potential of polycarbonate vectors for future in vivo application
      as an anticancer therapy. 

PMID- 25603324
TI  - Clostridium difficile infection in inflammatory bowel disease.

PMID- 25603323
TI  - Age-related changes in the diagnostic assessment of women with severe cervical
      lesions.
AB  - OBJECTIVES: To evaluate the effect of age on the diagnostic assessment of women
      with severe cervical intraepithelial neoplasia (CIN). METHODS: This retrospective
      observational study included 338 consecutive women with a diagnosis of CIN3 on
      cone specimen. Patients were divided into three groups according to age: < 35
      years (Group A), 35-49 years (Group B), and >= 50 years (Group C). Clinical and
      colposcopic variables were compared, and human papillomavirus (HPV) genotype
      distribution was measured. RESULTS: The most common HPV genotype was HPV-16
      (63.65%), followed by HPV-33 (7%), HPV-18 (6.2%), and HPV-31 (5.4%). The rate of
      the following high-grade lesion predictors was lower in Group C than in Groups A
      and B: HPV-16 infections (55.9% vs. 75% vs. 70.9%, respectively, p = 0.022); high
      grade colposcopic impression (29.4% vs. 51.8% vs. 51.7%, respectively, p <
      0.0001); and high-grade cytological changes (30.9% vs. 56.2% vs. 45.4%,
      respectively, p = 0.025). An endocervical lesion location was more frequent in
      Group C than in Groups A and B (55.6% vs. 6.8% vs. 11.8%, respectively, p <
      0.0001). CONCLUSION: Women aged 50 years and older with CIN3 showed a significant
      reduction of high-grade lesion predictors along with physiological confounding
      cervical changes (transformation zone type 3 and endocervical lesion location).
      The diagnostic work-up of cervical lesions in older women should provide their
      potential consideration as a special population.

PMID- 25603325
TI  - Risk factors for Clostridium difficile diarrhea in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Despite the growing incidence of Clostridium difficile diarrhea (CCD)
      in patients with inflammatory bowel disease (IBD), little is known about the
      associated risk factors. METHOD: A retrospective study comparing cases of CCD in
      patients with IBD to IBD carriers who did not develop CCD. A comparison was also
      made with patients who developed CCD but did not suffer IBD. RESULTS: Three cases
      (20%) with IBD and CCD had received antibiotics during the previous three months
      versus none of the controls (IBD without CCD, p = 0.22). Ten cases (67%) received
      treatment with proton pump inhibitors (PPIs) versus 2 (13%) in the control group
      (IBD without CCD, p = 0.001). Seven cases underwent colonoscopy and
      pseudomembranes were seen in one (14%). Fourteen (93%) patients demonstrated a
      favourable response to metronidazole. Patients with IBD and CCD presented with
      younger age (36 +/- 10 years), a higher degree of community-acquired infection
      (13 patients, 87%), immunosuppressive treatment (7 patients, 47%) and less
      patients had received previous antibiotic treatment (3 patients, 20%) than those
      with CCD without IBD. The proportion of patients who received treatment with PPIs
      was similar (66% and 80%, respectively p = 0.266). CONCLUSIONS: CCD in IBD
      carriers affects younger patients, the majority are community acquired (less
      nosocomial) and it is more related to previous treatment with PPIs than with the
      antibiotic treatment. Clinical evolution is also favourable.

PMID- 25603326
TI  - Association of NAFLD with subclinical atherosclerosis and coronary-artery
      disease: meta-analysis.
AB  - BACKGROUND: Recent studies have associated non-alcoholic fatty liver disease
      (NAFLD) with increased risk of cardiovascular disease, using tests of subclinical
      atherosclerosis. AIM: To evaluate the influence of NAFLD on subclinical
      atherosclerosis and coronary artery disease (CAD). METHODS: We reviewed Pubmed
      and EMBASE. According to inclusion and exclusion criteria, we selected 14 studies
      and were classified in two groups. Ten studies aimed the presence of subclinical
      atherosclerosis and four studies the presence of coronary artery disease. To
      assess subclinical atherosclerosis, we selected studies with pathological carotid
      intima-media thickness (CIMT) and with presence of carotid plaques. We considered
      coronary artery disease when patients showed at least 50% stenosis at one or more
      major coronary arteries. NAFLD was assessed by ultrasound (US) and liver biopsy.
      RESULTS: NAFLD showed a higher prevalence of pathological CIMT [35.1% (351/999)
      vs. 21.8% (207/948); p < 0.0001], with OR 2.04 (95% CI: 1.65-2.51). Similarly,
      the presence of carotid plaques was higher in NAFLD diagnosed by US [34.2%
      (101/295) vs. 12.9% (51/394); p < 0.0001] [OR 2.82 (95% CI: 1.87-4.27)] and
      diagnosed by liver biopsy [64.8% (70/108) vs. 31.3% (59/188); p < 0.0001] [OR
      4.41 (95% CI: 2.63-7.40)]. On the other hand, four studies assessed CAD in
      patients underwent coronary angiogram. Subjects with NAFLD showed 80.4% (492/612)
      of CAD, while it was detected in 60.7% (356/586) (p < 0.0001) in patients without
      NAFLD. Therefore, NAFLD was associated with a remarkably higher likelihood of
      CAD, using random effects model [OR 3.31 (95% CI: 2.21-4.95)] or fixed effects
      model [OR 3.13 (95% CI: 2.36-4.16)]. CONCLUSIONS: NAFLD increases the risk of
      subclinical atherosclerosis and coronary artery disease. The right management of
      these patients could modify the natural history both liver and cardiovascular
      disease.

PMID- 25603327
TI  - Ischemic etiopathogenesis as the possible origin of post-double baloon
      enteroscopy pancreatitis. A porcine model study.
AB  - The aim is to evaluate the pancreatic vascular-ischemic effects related to double
      balloon enteroscopy in the porcine model as a possible etiopathogenesis of post
      enteroscopic pancreatitis. For this reason we carry out two independent
      experiments in a porcine animal model. In the first arm protocol (group I), 10
      animals underwent 90 minutes of oral enteroscopy with 7 days follow-up.The levels
      of amylase, lipase and C-reactive protein were measured at T0 basal-T1 -90 min,
      T2-24, T3-7 days. Also we perform upper gastrointestinal endoscopy in a control
      group. At 7 days, the animals of experimental protocol-I had their pancreases
      removed for a pathological and immunohistochemical study to evaluate vascular
      epithelial growth factor (VEGF) expression.The second experimental protocol in
      this study aims to evaluate possible changes in vascular topography due to the
      double balloon enteroscopy (DBE). Group-II (10 animals) underwent oral
      enteroscopy and selective angiography of the cranial mesenteric artery and celiac
      trunk. None of the group I or control group animals presented pancreatitis,
      although the biochemical results for group-I showed increases in the levels of
      amylase, lipase and C reactive protein at 24 hours. The microscopic study for
      group-I showed pancreatic necrotic foci and positive VEGF expression, though
      these changes were not expressed in the control group.These foci were found in
      50% of the group I animals and in relation to the total of the parenchyma were
      quantified at 6% of the pancreas. The results for group-II showed that the
      enteroscopy caused mobilization of the mesenteric vascular axis, with signs of
      both intestinal and pancreatic hypoperfusion. The conclusions of this study are
      that, after enteroscopy in the porcine model, pancreatic necrotic foci are
      produced, in addition to ischemic phenomena causing VEGF expression. This could
      be related to episodes of visceral hypoperfusion caused by vascular alterations
      on a topographic level. This can be related to the possible ischemic
      etiopathogenesis described for post-enteroscopic pancreatitis.

PMID- 25603328
TI  - Evaluation of bariatric surgery patients at the emergency department of a
      tertiary referral hospital.
AB  - OBJECTIVE: To describe the profile of the bariatric surgery patients that were
      admitted to the Emergency Department (ED). METHOD: A retrospective review of the
      reasons why bariatric surgery patients go to our ED. We analyzed the first 30
      days after the surgery. We evaluated the number and indications of admissions,
      the examinations ordered, and final diagnosis and destination of the patients.
      RESULTS: From January 2010 to July 2012, 320 patients underwent bariatric surgery
      at our Institution. Fifty three patients (16.6%) were admitted to the ED at least
      once. We found 58 admissions (1.1 admissions by patient). Patients who had
      duodenal switch and Roux-en-Y gastric bypass were the most representative (74%).
      The main indications for admission were abdominal pain (50%), and problems
      related to the surgical wounds (22.4%). Blood test was the most performed
      examination (75.9%). The most frequent final diagnosis was unspecific abdominal
      pain in 27 cases (46.6%), and complications of the surgical wound in 10 patients
      (17.2%). Nineteen patients (35.84%) were admitted to the surgical ward from the
      ED, and 5 of them required surgical revision (9.4%). Multivariate analyses showed
      that the type of surgery was the only predictor variable for the ED admission.
      CONCLUSIONS: Attending ED after bariatric surgery is not common, and less than a
      third of the patients required hospital admission. Just a small percentage of the
      examinations showed any pathological value. Readmission rate is very low.
      Surgical procedure is the only predictor for ED admission.

PMID- 25603329
TI  - Proton pump inhibitor-responsive esophageal eosinophilia: a historical
      perspective on a novel and evolving entity.
AB  - Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease, first
      described in 1993, with a steadily increasing incidence and prevalence in western
      countries. Over the 80's and early 90's, dense esophageal eosinophilia was mostly
      associated gastroesophageal reflux disease (GERD). For the next 15 years, EoE and
      GERD were rigidly considered separate entities: Esophageal eosinophilia with
      pathological acid exposure on pH monitoring or response to proton pump inhibitor
      (PPI) therapy was GERD, whereas normal pH monitoring or absence of response to
      PPIs was EoE. Updated guidelines in 2011 described a novel phenotype, proton pump
      inhibitor-responsive esophageal eosinophilia (PPI-REE), referring to patients who
      appear to have EoE clinically, but who achieve complete remission after PPI
      therapy. Currently, PPI-REE must be formally excluded before diagnosing EoE,
      since 30-40% of patients with suspected EoE are eventually diagnosed with PPI
      REE.Interestingly, PPI-REE and EoE remain undistinguishable based on clinical,
      endoscopic, and histological findings, pH monitoring, and measurement of tissue
      markers and cytokines related to eosinophilic inflammation.This review article
      aims to revisit the relatively novel concept of PPI-REE from a historical
      perspective, given the strong belief that only GERD, as an acid peptic disorder,
      could respond to the acid suppressing ability of PPI therapy, is becoming
      outdated. Evolving evidence suggests that PPI-REE is genetically and
      phenotypically undistinguishable from EoE and PPI therapy alone can almost
      completely reverse allergic inflammation. As such, PPI-REE might constitute a
      subphenotype of EoE and PPI therapy may be the first therapeutic step and diet/
      steroids may represent step up therapy. Possibly, the term PPI-REE will be soon
      replaced by PPI-responsive EoE. The mechanism as to why some patients respond to
      PPI therapy (PPI-REE) while others do not (EoE), remains to be elucidated.

PMID- 25603330
TI  - Inflammatory fibroid polyp of the appendix or Vanek's tumor.

PMID- 25603331
TI  - Acute abdomen for lymphangioma of the small bowel mesentery: a case report and
      review of the literature.
AB  - Systemic lupus erithematosus (SLE) is an autoimmune disease with multiorgan
      involvement caused principally by vasculitis of small vessels. The
      gastrointestinal tract is one of the most frequently affected by SLE, with
      abdominal pain as the most common symptom. An early diagnosis and treatment of
      lupus enteritis is essential to avoid complications like hemorrhage or
      perforation, with up to 50 % of mortality rate. However, differential diagnosis
      sometimes is difficult, especially with other types of gastrointestinal diseases
      as digestive involvement of antiphospholipid syndrome (APS), moreover when both
      entities may coexist. We describe the case of a patient with both diseases that
      was diagnosed with lupus enteritis and treated with steroid therapy; the patient
      had an excellent response. 

PMID- 25603332
TI  - Acute abdomen in patients with systemic lupus erythematosus and antiphospholipid
      syndrome. Importance of early diagnosis and treatment.
AB  - Systemic lupus erithematosus (SLE) is an autoimmune disease with multiorgan
      involvement caused principally by vasculitis of small vessels. The
      gastrointestinal tract is one of the most frequently affected by SLE, with
      abdominal pain as the most common symptom. An early diagnosis and treatment of
      lupus enteritis is essential to avoid complications like hemorrhage or
      perforation, with up to 50 % of mortality rate. However, differential diagnosis
      sometimes is difficult, especially with other types of gastrointestinal diseases
      as digestive involvement of antiphospholipid syndrome (APS), moreover when both
      entities may coexist. We describe the case of a patient with both diseases that
      was diagnosed with lupus enteritis and treated with steroid therapy; the patient
      had an excellent response. 

PMID- 25603334
TI  - [Gastric varices].

PMID- 25603333
TI  - Eosinophilic cholecystitis: an infrequent cause of acute cholecystitis.
AB  - Eosinophilic cholecystitis (EC) is a rare disease that is characterised by
      eosinophilic infiltration of the gallbladder. Its pathogenesis is unknown,
      although many hypotheses have been made. Clinical and laboratory manifestations
      do not differ from those of other causes of cholecystitis. Diagnosis is
      histological and usually performed after analysis of the surgical specimen. We
      report the case of a woman aged 24 years, with symptoms of fever, vomiting and
      pain in the right upper quadrant. When imaging tests revealed acalculous
      cholecystitis, an urgent cholecystectomy was performed. Histological examination
      of the surgical specimen revealed eosinophilic cholecystitis. No cause of the
      symptoms was found. 

PMID- 25603335
TI  - Correlation between location of amyloid deposits and endoscopic and clinical
      manifestations in symptomatic gastrointestinal amyloidosis.

PMID- 25603336
TI  - Liver abscess due to Klebsiella pneumoniae and its relation to colon lesions

PMID- 25603337
TI  - Vacuolar internal anal sphincter myophaty as a rare cause of proctalgia fugax and
      constipation.

PMID- 25603338
TI  - 13 cm GIST in 19-year-old patient, is it the first manifestation of Carney triad?

PMID- 25603339
TI  - Results of a nation-wide survey on hypolactasia--how is this condition diagnosed
      and managed in our setting?

PMID- 25603341
TI  - Ophiobolin O isolated from Aspergillus ustus induces G1 arrest of MCF-7 cells
      through interaction with AKT/GSK3beta/cyclin D1 signaling.
AB  - Ophiobolin O is a member of ophiobolin family, which has been proved to be a
      potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor
      effect and the mechanism of ophiobolin O remain unclear. In this study, we
      further verified ophiobolin O-induced G1 phase arrest in human breast cancer MCF
      7 cells, and found that ophiobolin O reduced the phosphorylation level of AKT and
      GSK3beta, and induced down-regulation of cyclin D1. The inverse docking (INVDOCK)
      analysis indicated that ophiobolin O could bind to GSK3beta, and GSK3beta
      knockdown abolished cyclin D1 degradation and G1 phase arrest. Pre-treatment with
      phosphatase inhibitor sodium or thovanadate halted dephosphorylation of AKT and
      GSK3beta, and blocked ophiobolin O-induced G1 phase arrest. These data suggest
      that ophiobolin O may induce G1 arrest in MCF-7 cells through interaction with
      AKT/GSK3beta/cyclin D1 signaling. In vivo, ophiobolin O suppressed tumor growth
      and showed little toxicity in mouse xenograft models. Overall, these findings
      provide theoretical basis for the therapeutic use of ophiobolin O. 

PMID- 25603340
TI  - Magnetotactic bacteria as potential sources of bioproducts.
AB  - Magnetotactic bacteria (MTB) produce intracellular organelles called magnetosomes
      which are magnetic nanoparticles composed of magnetite (Fe3O4) or greigite
      (Fe3S4) enveloped by a lipid bilayer. The synthesis of a magnetosome is through a
      genetically controlled process in which the bacterium has control over the
      composition, direction of crystal growth, and the size and shape of the mineral
      crystal. As a result of this control, magnetosomes have narrow and uniform size
      ranges, relatively specific magnetic and crystalline properties, and an
      enveloping biological membrane. These features are not observed in magnetic
      particles produced abiotically and thus magnetosomes are of great interest in
      biotechnology. Most currently described MTB have been isolated from saline or
      brackish environments and the availability of their genomes has contributed to a
      better understanding and culturing of these fastidious microorganisms. Moreover,
      genome sequences have allowed researchers to study genes related to magnetosome
      production for the synthesis of magnetic particles for use in future commercial
      and medical applications. Here, we review the current information on the biology
      of MTB and apply, for the first time, a genome mining strategy on these
      microorganisms to search for secondary metabolite synthesis genes. More
      specifically, we discovered that the genome of the cultured MTB Magnetovibrio
      blakemorei, among other MTB, contains several metabolic pathways for the
      synthesis of secondary metabolites and other compounds, thereby raising the
      possibility of the co-production of new bioactive molecules along with
      magnetosomes by this species. 

PMID- 25603342
TI  - Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A
      and B, chlorinated thiazole-containing peptide/polyketides from the Caribbean
      sponge, Smenospongia aurea.
AB  - The study of the secondary metabolites contained in the organic extract of
      Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3)
      and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid
      tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at
      nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic
      mechanism. 

PMID- 25603343
TI  - Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines
      and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogues.
AB  - Two new series of nortopsentin analogues, in which the imidazole ring of the
      natural product was replaced by thiazole and indole units were both substituted
      by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion,
      were efficiently synthesized. Compounds belonging to both series inhibited the
      growth of HCT-116 colorectal cancer cells at low micromolar concentrations,
      whereas they did not affect the viability of normal-like intestinal cells. A
      compound of the former series induced apoptosis, evident as externalization of
      plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans
      membrane potential, while blocking the cell cycle in G2/M phase. In contrast, a
      derivative of the latter series elicited distinct responses in accordance with
      the dose. Thus, low concentrations (GI30) induced morphological changes
      characteristic of autophagic death with massive formation of cytoplasmic acid
      vacuoles without apparent loss of nuclear material, and with arrest of cell cycle
      at the G1 phase, whereas higher concentrations (GI70) induced apoptosis with
      arrest of cell cycle at the G1 phase. 

PMID- 25603344
TI  - Identification of a 4-deoxy-L-erythro-5-hexoseulose uronic acid reductase, FlRed,
      in an alginolytic bacterium Flavobacterium sp. strain UMI-01.
AB  - In alginate-assimilating bacteria, alginate is depolymerized to unsaturated
      monosaccharide by the actions of endolytic and exolytic alginate lyases (EC
      4.2.2.3 and EC 4.2.2.11). The monosaccharide is non-enzymatically converted to 4
      deoxy-L-ery thro-5-hexoseulose uronic acid (DEH), then reduced to 2-keto-3-deoxy
      D-gluconate (KDG) by a specific reductase, and metabolized through the Entner
      Doudoroff pathway. Recently, the NADPH-dependent reductase A1-R that belongs to
      short-chain dehydrogenases/reductases (SDR) superfamily was identified as the DEH
      reductase in Sphingomonas sp. A1. We have subsequently noticed that an SDR-like
      enzyme gene, flred, occurred in the genome of an alginolytic bacterium
      Flavobacterium sp. strain UMI-01. In the present study, we report on the deduced
      amino-acid sequence of flred and DEH-reducing activity of recombinant FlRed. The
      deduced amino-acid sequence of flred comprised 254 residues and showed 34% amino
      acid identities to that of A1-R from Sphingomonas sp. A1 and 80%-88% to those of
      SDR-like enzymes from several alginolytic bacteria. Common sequence motifs of SDR
      superfamily enzymes, e.g., the catalytic tetrad Asn-Lys-Tyr-Ser and the cofactor
      binding sequence Thr-Gly-x-x-x-Gly-x-Gly in Rossmann fold, were completely
      conserved in FlRed. On the other hand, an Arg residue that determined the NADPH
      specificity of Sphingomonas A1-R was replaced by Glu in FlRed. Thus, we
      investigated cofactor-preference of FlRed using a recombinant enzyme. As a
      result, the recombinant FlRed (recFlRed) was found to show high specificity to
      NADH. recFlRed exhibited practically no activity toward variety of aldehyde,
      ketone, keto ester, keto acid and aldose substrates except for DEH. On the basis
      of these results, we conclude that FlRed is the NADH-dependent DEH-specific SDR
      of Flavobacterium sp. strain UMI-01.

PMID- 25603345
TI  - Profiling of the molecular weight and structural isomer abundance of macroalgae
      derived phlorotannins.
AB  - Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5
      trihydroxybenzene) unique to macroalgae. These phenolic compounds are integral
      structural components of the cell wall in brown algae, but also play many
      secondary ecological roles such as protection from UV radiation and defense
      against grazing. This study employed Ultra Performance Liquid Chromatography
      (UPLC) with tandem mass spectrometry to investigate isomeric complexity and
      observed differences in phlorotannins derived from macroalgae harvested off the
      Irish coast (Fucus serratus, Fucus vesiculosus, Himanthalia elongata and
      Cystoseira nodicaulis). Antioxidant activity and total phenolic content assays
      were used as an index for producing phlorotannin fractions, enriched using
      molecular weight cut-off dialysis with subsequent flash chromatography to profile
      phlorotannin isomers in these macroalgae. These fractions were profiled using
      UPLC-MS with multiple reaction monitoring (MRM) and the level of isomerization
      for specific molecular weight phlorotannins between 3 and 16 monomers were
      determined. The majority of the low molecular weight (LMW) phlorotannins were
      found to have a molecular weight range equivalent to 4-12 monomers of
      phloroglucinol. The level of isomerization within the individual macroalgal
      species differed, resulting in substantially different numbers of phlorotannin
      isomers for particular molecular weights. F. vesiculosus had the highest number
      of isomers of 61 at one specific molecular mass, corresponding to 12
      phloroglucinol units (PGUs). These results highlight the complex nature of these
      extracts and emphasize the challenges involved in structural elucidation of these
      compounds. 

PMID- 25603346
TI  - Development of highly selective Kv1.3-blocking peptides based on the sea anemone
      peptide ShK.
AB  - ShK, from the sea anemone Stichodactyla helianthus, is a 35-residue disulfide
      rich peptide that blocks the voltage-gated potassium channel Kv1.3 at ca. 10 pM
      and the related channel Kv1.1 at ca. 16 pM. We developed an analog of this
      peptide, ShK-186, which is currently in Phase 1b-2a clinical trials for the
      treatment of autoimmune diseases such as multiple sclerosis and rheumatoid
      arthritis. While ShK-186 displays a >100-fold improvement in selectivity for
      Kv1.3 over Kv1.1 compared with ShK, there is considerable interest in developing
      peptides with an even greater selectivity ratio. In this report, we describe
      several variants of ShK that incorporate p-phophono-phenylalanine at the N
      terminus coupled with internal substitutions at Gln16 and Met21. In addition, we
      also explored the combinatorial effects of these internal substitutions with an
      alanine extension at the C-terminus. Their selectivity was determined by patch
      clamp electrophysiology on Kv1.3 and Kv1.1 channels stably expressed in mouse
      fibroblasts. The peptides with an alanine extension blocked Kv1.3 at low pM
      concentrations and exhibited up to 2250-fold selectivity for Kv1.3 over Kv1.1.
      Analogs that incorporates p-phosphono-phenylalanine at the N-terminus blocked
      Kv1.3 with IC50s in the low pM range and did not affect Kv1.1 at concentrations
      up to 100 nM, displaying a selectivity enhancement of >10,000-fold for Kv1.3 over
      Kv1.1. Other potentially important Kv channels such as Kv1.4 and Kv1.6 were only
      partially blocked at 100 nM concentrations of each of the ShK analogs. 

PMID- 25603347
TI  - Activation of p53 with ilimaquinone and ethylsmenoquinone, marine sponge
      metabolites, induces apoptosis and autophagy in colon cancer cells.
AB  - The tumor suppressor, p53, plays an essential role in the cellular response to
      stress through regulating the expression of genes involved in cell cycle arrest,
      apoptosis and autophagy. Here, we used a cell-based reporter system for the
      detection of p53 response transcription to identify the marine sponge
      metabolites, ilimaquinone and ethylsmenoquinone, as activators of the p53
      pathway. We demonstrated that ilimaquinone and ethylsmenoquinone efficiently
      stabilize the p53 protein through promotion of p53 phosphorylation at Ser15 in
      both HCT116 and RKO colon cancer cells. Moreover, both compounds upregulate the
      expression of p21WAF1/CIP1, a p53-dependent gene, and suppress proliferation of
      colon cancer cells. In addition, ilimaquinone and ethylsmenoquinone induced G2/M
      cell cycle arrest and increased caspase-3 cleavage and the population of cells
      that positively stained with Annexin V-FITC, both of which are typical
      biochemical markers of apoptosis. Furthermore, autophagy was elicited by both
      compounds, as indicated by microtubule-associated protein 1 light chain 3 (LC3)
      puncta formations and LC3-II turnover in HCT116 cells. Our findings suggest that
      ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by activation
      of the p53 pathway and may have significant potential as chemo-preventive and
      therapeutic agents for human colon cancer. 

PMID- 25603348
TI  - Enzyme-assisted extraction of bioactive material from Chondrus crispus and Codium
      fragile and its effect on herpes simplex virus (HSV-1).
AB  - Codium fragile and Chondrus crispus are, respectively, green and red seaweeds
      which are abundant along the North Atlantic coasts. We investigated the chemical
      composition and antiviral activity of enzymatic extracts of C. fragile (CF) and
      C. crispus (CC). On a dry weight basis, CF consisted of 11% protein, 31% neutral
      sugars, 0.8% sulfate, 0.6% uronic acids, and 49% ash, while CC contained 27%
      protein, 28% neutral sugars, 17% sulfate, 1.8% uronic acids, and 25% ash. Enzyme
      assisted hydrolysis improved the extraction efficiency of bioactive materials.
      Commercial proteases and carbohydrases significantly improved (p <= 0.001)
      biomass yield (40%-70% dry matter) as compared to aqueous extraction (20%-25% dry
      matter). Moreover, enzymatic hydrolysis enhanced the recovery of protein, neutral
      sugars, uronic acids, and sulfates. The enzymatic hydrolysates exhibited
      significant activity against Herpes simplex virus (HSV-1) with EC50 of 77.6-126.8
      MUg/mL for CC and 36.5-41.3 MUg/mL for CF, at a multiplicity of infection (MOI)
      of 0.001 ID50/cells without cytotoxity (1-200 MUg/mL). The extracts obtained from
      proteases (P1) and carbohydrases (C3) were also effective at higher virus MOI of
      0.01 ID50/cells without cytotoxity. Taken together, these results indicate the
      potential application of enzymatic hydrolysates of C. fragile and C. crispus in
      functional food and antiviral drug discovery. 

PMID- 25603349
TI  - Biosynthesis of akaeolide and lorneic acids and annotation of type I polyketide
      synthase gene clusters in the genome of Streptomyces sp. NPS554.
AB  - The incorporation pattern of biosynthetic precursors into two structurally unique
      polyketides, akaeolide and lorneic acid A, was elucidated by feeding experiments
      with 13C-labeled precursors. In addition, the draft genome sequence of the
      producer, Streptomyces sp. NPS554, was performed and the biosynthetic gene
      clusters for these polyketides were identified. The putative gene clusters
      contain all the polyketide synthase (PKS) domains necessary for assembly of the
      carbon skeletons. Combined with the 13C-labeling results, gene function
      prediction enabled us to propose biosynthetic pathways involving unusual carbon
      carbon bond formation reactions. Genome analysis also indicated the presence of
      at least ten orphan type I PKS gene clusters that might be responsible for the
      production of new polyketides. 

PMID- 25603350
TI  - Structure elucidation of new acetylated saponins, Lessoniosides A, B, C, D, and
      E, and non-acetylated saponins, Lessoniosides F and G, from the viscera of the
      sea cucumber Holothuria lessoni.
AB  - Sea cucumbers produce numerous compounds with a wide range of chemical structural
      diversity. Among these, saponins are the most diverse and include sulfated, non
      sulfated, acetylated and methylated congeners with different aglycone and sugar
      moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive
      ion mode, were used to elucidate the structure of new saponins extracted from the
      viscera of H. lessoni. Fragmentation of the aglycone provided structural
      information on the presence of the acetyl group. The presence of the O-acetyl
      group was confirmed by observing the mass transition of 60 u corresponding to the
      loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage
      provided information on the mass of the aglycone (core), and the sequence and
      type of monosaccharides that constitute the sugar moiety. The tandem mass spectra
      of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural
      information on the glycosidic bond cleavages. As a result, and in conjunction
      with existing literature, we characterized the structure of five new acetylated
      saponins, Lessoniosides A-E, along with two non-acetylated saponins Lessoniosides
      F and G at m/z 1477.7, which are promising candidates for future drug
      development. The presented strategy allows a rapid, reliable and complete
      analysis of native saponins. 

PMID- 25603352
TI  - Application of multiple-locus variable number tandem repeat analysis to identify
      outbreak-associated Neisseria meningitides serogroup C sequence type 4821 in
      China.
AB  - Neisseria meningitidis (N. meningitidis) serogroup C sequence type (ST)-4821
      caused an outbreak in 2010 in Shandong province of China. Twenty-one non-outbreak
      associated strains were isolated, along with twenty-eight N. meningitides
      serogroup C ST-4821 isolates. Therefore, it's essential to identify and clarify
      characterization of the real outbreak-associated strains with a rapid method
      during an outbreak investigation. In this study, multiple-locus variable number
      tandem repeat analysis (MLVA) was applied to analyze 84 N. meningitidis strains,
      among which 58 were recovered from two outbreaks and 26 were sporadic isolates.
      Three MLVA schemes with different combination of VNTR loci were tested, and two
      of them were suitable for isolates from China: scheme 2 with six loci was found
      to separate ST into finer resolution, and scheme 3 with five loci can be used to
      identify outbreak-associated isolates from the same outbreak that caused by N.
      meningitidis serogroup C ST-4821. 

PMID- 25603351
TI  - Marine peptides and their anti-infective activities.
AB  - Marine bioresources are a valuable source of bioactive compounds with industrial
      and nutraceutical potential. Numerous clinical trials evaluating novel
      chemotherapeutic agents derived from marine sources have revealed novel
      mechanisms of action. Recently, marine-derived bioactive peptides have attracted
      attention owing to their numerous beneficial effects. Moreover, several studies
      have reported that marine peptides exhibit various anti-infective activities,
      such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti
      tuberculosis, and antiviral activities. In the last several decades, studies of
      marine plants, animals, and microbes have revealed tremendous number of
      structurally diverse and bioactive secondary metabolites. However, the treatments
      available for many infectious diseases caused by bacteria, fungi, and viruses are
      limited. Thus, the identification of novel antimicrobial peptides should be
      continued, and all possible strategies should be explored. In this review, we
      will present the structures and anti-infective activity of peptides isolated from
      marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the
      present. 

PMID- 25603353
TI  - Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and
      photodynamic therapeutic effects.
AB  - Recently, plasmonic copper sulfide (Cu2-xS) nanocrystals (NCs) have attracted
      much attention as materials for photothermal therapy (PTT). Previous reports have
      correlated photoinduced cell death to the photothermal heat mechanism of these
      NCs, and no evidence of their photodynamic properties has been reported yet.
      Herein we have prepared physiologically stable near-infrared (NIR) plasmonic
      copper sulfide NCs and analyzed their photothermal and photodynamic properties,
      including therapeutic potential in cultured melanoma cells and a murine melanoma
      model. Interestingly, we observe that, besides a high PTT efficacy, these copper
      sulfide NCs additionally possess intrinsic NIR induced photodynamic activity,
      whereupon they generate high levels of reactive oxygen species. Furthermore, in
      vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited.
      This study highlights a mechanism of NIR light induced cancer therapy, which
      could pave the way toward more effective nanotherapeutics. 

PMID- 25603355
TI  - [How to delegate correctly - Transferring physicians' tasks to assistance
      personnel].

PMID- 25603354
TI  - Engagement of DYRK2 in proper control for cell division.
AB  - Dysregulation of cell cycle machinery causes abnormal cell division, leading to
      cancer development. To drive cell cycle properly, expression levels of cell cycle
      regulators are tightly regulated through the cell cycle. Dual specificity
      tyrosine phosphorylation-regulated kinase 2 (DYRK2) is a Ser/Thr kinase, and its
      intracellular functions had not been elucidated for decades. Recent studies have
      shown that DYRK2 down-regulates key molecules on cell cycle control. This review
      mainly highlights the DYRK2 function during cell division. In addition, we
      summarize tumor suppressive role of DYRK2 in cancer cells and discuss future
      research directions for DYRK2 toward the novel cancer therapies.

PMID- 25603356
TI  - Self-assembly and nanoaggregation of a pH responsive DNA hybrid amphiphile.
AB  - This work describes the design and preparation of a simple but novel hybrid
      amphiphile containing a pH-responsive DNA sequence. The formation of a
      bimolecular i-motif structure allows the control of reversible switching of the
      hybrid amphiphile between the dimer and unimer by pH. Thus, spherical aggregates
      with distinct self-assembly pathways, sizes and structures are obtained at pH 4.5
      and pH 9.0, and the structures can be switched by the change of pH and thermal
      annealing. This work reports different self-assembled nanostructures and their
      transitions that give this amphiphile potential for the design of controllable
      drug delivery systems. 

PMID- 25603357
TI  - "It is what it is": masculinity, homosexuality, and inclusive discourse in mixed
      martial arts.
AB  - In this article we make use of inclusive masculinity theory to explore online
      media representations of male homosexuality and masculinity within the
      increasingly popular combat sport of mixed martial arts (MMA). Adopting a case
      study approach, we discuss narratives constructed around one aspirational male
      MMA fighter, Dakota Cochrane, whose history of having participated in gay
      pornography became a major talking point on a number of MMA discussion/community
      Web sites during early 2012. While these narratives attempted to discursively
      rescue Cochrane's supposedly threatened masculinity, highlighting both his "true"
      heterosexuality and his prodigious fighting abilities, they also simultaneously
      celebrated the acceptance of homosexual men within the sport that Cochrane's case
      implied. Thus, we suggest that these media representations of homosexuality and
      masculinity within MMA are indicative of declining cultural homophobia and
      homohysteria and an inclusive vision of masculinity, as previously described by
      proponents of inclusive masculinity theory. 

PMID- 25603358
TI  - Neural processing of social participation in borderline personality disorder and
      social anxiety disorder.
AB  - Patients with borderline personality disorder (BPD) and patients with social
      anxiety disorder (SAD) are known to be highly sensitive to social rejection.
      Social information processing is assumed to play a key role for this shared
      psychopathological phenomenon. The first steps in social information processing
      are to encode social cues and to create a mental representation of the social
      situation. The aim of the current study was to test whether the perception of
      social participation in patients with BPD and patients with SAD is biased in this
      initial stage of social processing. Focus was on the P3b, a brain potential
      related to stimulus evaluation that has been shown to be a sensitive indicator
      for the processes of interest. Twenty five unmedicated patients with BPD, 25
      unmedicated patients with SAD and 25 healthy controls (HC) played an EEG
      compatible version of Cyberball, a virtual ball-tossing paradigm that
      experimentally induces social inclusion and exclusion. All participants showed a
      pronounced P3b when excluded. Only patients with BPD showed an enhanced P3b also
      during the inclusion condition, indicating altered processing of social
      inclusion. The EEG results for the BPD group were consistent with their self
      report data. Patients with BPD felt more excluded during the inclusion condition
      of Cyberball than both HC and patients with SAD. Furthermore, heightened
      rejection expectancy (subscale of the Rejection Sensitivity Questionnaire) was
      associated with a smaller difference in the P3b amplitude between inclusion and
      exclusion. Results indicate a negatively biased perception of social inclusion in
      BPD already during the initial stage of social processing.

PMID- 25603359
TI  - Unraveling affective dysregulation in borderline personality disorder: a
      theoretical model and empirical evidence.
AB  - Although emotion dysregulation has consistently been conceptualized as a core
      problem of borderline personality disorder (BPD), a comprehensive, and
      empirically and ecologically validated model that captures the exact types of
      dysregulation remains absent. In the present article, we combine insights from
      basic affective science and the biosocial theory of BPD to present a theoretical
      model that captures the most fundamental affective dynamical processes that
      underlie BPD and stipulates that individuals with BPD are characterized by more
      negative affective homebases, higher levels of affective variability, and lower
      levels of attractor strength or return to baseline. Next, we empirically validate
      this proposal by statistically modeling data from three electronic diary studies
      on emotional responses to personally relevant stimuli in personally relevant
      environments that were collected both from patients with BPD (N = 50, 42, and 43)
      and from healthy subjects (N = 50, 24, and 28). The results regarding negative
      affective homebases and heightened affective variabilities consistently confirmed
      our hypotheses across all three datasets. The findings regarding attractor
      strengths (i.e., return to baseline) were less consistent and of smaller
      magnitude. The transdiagnostic nature of our approach may help to elucidate the
      common and distinctive mechanisms that underlie several different disorders that
      are characterized by affective dysregulation.

PMID- 25603360
TI  - Early starting, aggressive, and/or callous-unemotional? Examining the overlap and
      predictive utility of antisocial behavior subtypes.
AB  - Antisocial behavior (AB) in adolescence predicts problematic outcomes in
      adulthood. However, researchers have noted marked heterogeneity within the broad
      group of youth engaging in these destructive behaviors and have attempted to
      identify those with distinct etiologies and different trajectories of symptoms.
      In the present study, we evaluate 3 prominent AB subtyping approaches: age of
      onset, presence of callous-unemotional (CU) traits, and aggressive versus rule
      breaking symptoms. We examined the overlap of these subtypes and their predictive
      validity in a diverse sample of 268 low-income young men followed prospectively
      from adolescence into emerging adulthood. We found that those with early starting
      AB were uniquely high on aggressive symptoms but not on CU traits. Early starting
      AB and both aggression and rule breaking measured during adolescence predicted
      most subsequent psychiatric and AB outcomes in early adulthood in univariate
      models, whereas CU traits were only predictive of adolescent arrests, later
      substance dependence diagnosis, and later CU traits. Finally, after accounting
      for shared variance among predictor variables, we found that aggressive symptoms
      explained the most unique variance in predicting several later outcomes (e.g.,
      antisocial personality disorder) over and above other subtyping approaches.
      Results are discussed in relation to of the use of existing subtyping approaches
      to AB, noting that aggression and age of onset but not CU traits appear to be the
      best at predicting later negative outcome.

PMID- 25603362
TI  - Nonthermal Inactivation of Cronobacter sakazakii in Infant Formula Milk: A
      Review.
AB  - Up-to-date, nonthermal technologies and combinations of them, in accordance with
      the "hurdle technology" concept, are being applied by different research groups
      in response to calls by the International Food and Human Health Organizations
      (ESPGHAN, 2004; FAO/WHO, 2006, 2008) for alternatives to thermal control of
      Cronobacter sakazakii in reconstituted powdered infant formula milk. This review
      highlights (i) current knowledge on the application of nonthermal technologies to
      control C. sakazakii in infant formula milk and (ii) the importance of the
      application of nonthermal technologies for the control of C. sakazakii as part of
      the development of strategies in the context of improving food safety and quality
      of this product. 

PMID- 25603361
TI  - Factors of psychopathy and electrocortical response to emotional pictures:
      Further evidence for a two-process theory.
AB  - The Two-Process theory of psychopathy posits that distinct etiological mechanisms
      contribute to the condition: (a) a weakness in defensive (fear) reactivity
      related to affective-interpersonal features, and (b) impaired cognitive-executive
      functioning, marked by reductions in brain responses such as P3, related to
      impulsive-antisocial features. The current study examined relations between
      psychopathy factors and electrocortical response to emotional and neutral
      pictures in male offenders (N = 139) assessed using the Psychopathy Checklist
      Revised (PCL-R). Impulsive-antisocial features of the PCL-R (Factor 2) were
      associated with reduced amplitude of earlier P3 brain response to pictures
      regardless of valence, whereas the affective-interpersonal dimension (Factor 1)
      was associated specifically with reductions in late positive potential response
      to aversive pictures. Findings provide further support for the Two-Process theory
      and add to a growing body of evidence linking the impulsive-antisocial facet of
      psychopathy to the broader construct of externalizing proneness. Findings are
      discussed in terms of current initiatives directed at incorporating
      neuroscientific concepts into psychopathology classification. (PsycINFO Database
      Record 

PMID- 25603364
TI  - Live-cell techniques - advances and challenges.

PMID- 25603363
TI  - Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis
      patients: A double blind randomized clinical trial.
AB  - OBJECTIVES: Multiple sclerosis (MS) is the chronic inflammatory and demyelinating
      disorder of central nervous system which is accompanied with disability and
      negative life style changes such as fatigue and depression. The aim of this study
      is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue
      and depression in patients with MS. METHODS: We performed a randomized, double
      blinded, placebo-controlled trial to determine the effect of CoQ10 supplement
      (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means
      of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used
      to assess depressive symptoms. RESULTS: A significant decrease of FSS was
      observed in CoQ10 group during the intervention (P = 0.001) and significant
      increase of FSS change was observed within placebo group (P = 0.001). Repeated
      measure analysis of variance showed a significant time-by-treatment interaction
      for FSS (baseline 41.5 +/- 15.6 vs. endpoint 45 +/- 13.6; F1,45 = 55.23, P <
      0.001, eta(2) = 0.56) and BDI (baseline 17.8 +/- 12.2 vs. endpoint 20.4 +/- 11.4;
      F1,45 = 40.3, P < 0.001, eta(2) = 0.48), indicating significant decrease of FSS
      and BDI in CoQ10 group compared to placebo group. CONCLUSION: Our study suggests
      that CoQ10 supplementation (500 mg/day) can improve fatigue and depression in
      patients with multiple sclerosis.

PMID- 25603365
TI  - Proteomic approaches to uncover MMP function.
AB  - Proteomics has revolutionized protease research and particularly contributed to
      the identification of novel substrates and their sites of cleavage as key
      determinants of protease function. New technologies and rapid advancements in
      development of powerful mass spectrometers allowed unprecedented insights into
      activities of matrix metalloproteinases (MMPs) within their complex extracellular
      environments. Mass spectrometry-based proteomics extended our knowledge on MMP
      cleavage specificities and will help to develop more specific inhibitors as new
      therapeutics. Quantitative proteomics and N-terminal enrichment strategies have
      revealed numerous novel MMP substrates and shed light on their modes of action in
      vitro and in vivo. In this review, we provide an overview of current proteomic
      technologies in protease research and their application to the functional
      characterization of MMPs. 

PMID- 25603366
TI  - Unified method for the total pore volume and pore size distribution of
      hierarchical zeolites from argon adsorption and mercury intrusion.
AB  - A generalized approach to determine the complete distribution of macropores,
      mesopores, and micropores from argon adsorption and mercury porosimetry is
      developed and validated for advanced zeolite catalysts with hierarchically
      structured pore systems in powder and shaped forms. Rather than using a
      fragmented approach of simple overlays from individual techniques, a unified
      approach that utilizes a kernel constructed from model isotherms and model
      intrusion curves is used to calculate the complete pore size distribution and the
      total pore volume of the material. An added benefit of a single full-range pore
      size distribution is that the cumulative pore area and the area distribution are
      also obtained without the need for additional modeling. The resulting complete
      pore size distribution and the kernel accurately model both the adsorption
      isotherm and the mercury porosimetry. By bridging the data analysis of two
      primary characterization tools, this methodology fills an existing gap in the
      library of familiar methods for porosity assessment in the design of materials
      with multilevel porosity for novel technological applications. 

PMID- 25603367
TI  - Cognition from on high and down low: Verticality and construal level.
AB  - Across 7 studies, the authors examined the relationship between experiences of
      verticality and abstract versus concrete processing. Experiencing high, relative
      to low, verticality led to higher level identifications for actions (Study 1),
      greater willingness to delay short-term monetary gains for larger long-term
      monetary gains (Studies 2 and 5), and more frequent perceptions of meaningful
      relationships between objects and categories (Studies 3, 4, and 6), demonstrating
      that high verticality leads to more high-level construals. Mechanisms of these
      effects were explored, and the studies present evidence suggesting that mood
      (Studies 3 and 4), felt power (Study 4), arousal (Study 4), perceptual scope
      (Study 4), superficial semantic associations (Study 5), and movement (Study 5) do
      not mediate these effects. Instead, we found that even minimal experiences of
      verticality influence construal level (Study 6) and that verticality can
      influence construal level independent of the many plausible mediators.
      Furthermore, the relationship is reciprocal with abstract and concrete processing
      influencing the verticality of one's visual perspective (Study 7), suggesting an
      intimate link between construal level (abstract vs. concrete processing) and
      experiences of verticality.

PMID- 25603368
TI  - Editorial.
AB  - The incoming editor of Journal of Personality and Social Psychology:
      Interpersonal Relations and Group Processes discusses her plans to continue to
      encourage submission of a broad range of research related to interpersonal and
      group processes. She notes other goals for the new editorial team, which include
      encouraging the submission of high-quality multidisciplinary experiments that
      create a bridge between social psychology and other areas of research, decreasing
      the amount of time that a manuscript spends under review by adopting a number of
      important new strategies, and continuing the discussion concerning good empirical
      practice.

PMID- 25603369
TI  - The equilibrium model of relationship maintenance.
AB  - A new equilibrium model of relationship maintenance is proposed. People can
      protect relationship bonds by practicing 3 threat-mitigation rules: Trying to
      accommodate when a partner is hurtful, ensuring mutual dependence, and resisting
      devaluing a partner who impedes one's personal goals. A longitudinal study of
      newlyweds revealed evidence for the equilibrium model, such that relationship
      well-being (as indexed by satisfaction and commitment) declining from its usual
      state predicted increased threat-mitigation; in turn, increasing threat
      mitigation from its usual state predicted increased relationship well-being.
      Longitudinal findings further revealed adaptive advantages to uncertain trust.
      First, the match between trust and partner-risk predicted the trajectory of
      threat mitigation over time. People who hesitated to trust a high-risk partner
      became more likely to mitigate threats over 3 years, but people who hesitated to
      trust a safe partner became less likely to mitigate threats. The match between
      threat mitigation and partner-risk also predicted when being less trusting eroded
      later relationship well-being. Namely, when women paired with high-risk partners
      became more likely to mitigate threats, being less trusting at marriage lost its
      capacity to erode later relationship well-being.

PMID- 25603370
TI  - Zeroing in on heroes: a prototype analysis of hero features.
AB  - Heroes are ubiquitous in literature and popular discourse, yet little is known
      about cognitive representations of heroes. We examined lay conceptions of heroes
      using a prototype approach, compared heroes with other persons of influence, and
      studied how individuals use hero features to identify heroes. In Study 1,
      participants (N = 189) generated open-ended descriptions of heroes, which were
      sorted by independent coders into 26 meaningful categories. In Study 2,
      participants (N = 365) rated the centrality of these features, and subsequently
      classified each feature as either central (e.g., brave, moral integrity) or
      peripheral (e.g., humble, proactive). In a reaction time (RT) paradigm,
      participants in Study 3 (N = 33) identified central features of heroes faster
      than peripheral features. In Study 4, participants (N = 25) remembered more
      central hero features than peripheral features in a surprise recall task. In
      Study 5 (N = 89), participants most strongly identified a hero when the target
      was described with central features (vs. peripheral or neutral features). In
      Studies 6 (N = 212) and 7 (N = 307), participants' ratings evidenced that the
      prototypical features of heroes did not fit conceptually as well for role models
      and leaders. In all, these studies contribute new ideas to existing knowledge
      about heroes, and contribute to a shared understanding of what a hero means to
      people. Our research is thus an important step in refining heroism into a
      scientific concept. The notion of the prototypical features of heroes provides a
      basis for future hero research and intervention.

PMID- 25603374
TI  - Entitativity and intergroup bias: How belonging to a cohesive group allows people
      to express their prejudices.
AB  - We propose that people treat prejudice as more legitimate when it seems
      rationalistic-that is, linked to a group's pursuit of collective interests.
      Groups that appear to be coherent and unified wholes (entitative groups) are most
      likely to have such interests. We thus predicted that belonging to an entitative
      group licenses people to express prejudice against outgroups. Support for this
      idea came from 3 correlational studies and 5 experiments examining racial,
      national, and religious prejudice. The first 4 studies found that prejudice and
      discrimination seemed more socially acceptable to third parties when committed by
      members of highly entitative groups, because people could more easily explain
      entitative groups' biases as a defense of collective interests. Moreover, ingroup
      entitativity only lent legitimacy to outgroup prejudice when an interests-based
      explanation was plausible-namely, when the outgroup could possibly threaten the
      ingroup's interests. The last 4 studies found that people were more willing to
      express private prejudices when they perceived themselves as belonging to an
      entitative group. Participants' perceptions of their own race's entitativity were
      associated with a greater tendency to give explicit voice to their implicit
      prejudice against other races. Furthermore, experimentally raising participants'
      perceptions of ingroup entitativity increased explicit expressions of outgroup
      prejudice, particularly among people most likely to privately harbor such
      prejudices (i.e., highly identified group members). Together, these findings
      demonstrate that entitativity can lend a veneer of legitimacy to prejudice and
      disinhibit its expression. We discuss implications for intergroup relations and
      shifting national demographics. (PsycINFO Database Record (c) 2015 APA, all
      rights reserved). 

PMID- 25603373
TI  - Stereotypic vision: how stereotypes disambiguate visual stimuli.
AB  - Three studies examined how participants use race to disambiguate visual stimuli.
      Participants performed a first-person-shooter task in which Black and White
      targets appeared holding either a gun or an innocuous object (e.g., a wallet). In
      Study 1, diffusion analysis (Ratcliff, 1978) showed that participants rapidly
      acquired information about a gun when it appeared in the hands of a Black target,
      and about an innocuous object in the hands of a White target. For
      counterstereotypic pairings (armed Whites, unarmed Blacks), participants acquired
      information more slowly. In Study 2, eye tracking showed that participants relied
      on more ambiguous information (measured by visual angle from fovea) when
      responding to stereotypic targets; for counterstereotypic targets, they achieved
      greater clarity before responding. In Study 3, participants were briefly exposed
      to targets (limiting access to visual information) but had unlimited time to
      respond. In spite of their slow, deliberative responses, they showed racial bias.
      This pattern is inconsistent with control failure and suggests that stereotypes
      influenced identification of the object. All 3 studies show that race affects
      visual processing by supplementing objective information.

PMID- 25603371
TI  - The emergence of sex differences in personality traits in early adolescence: A
      cross-sectional, cross-cultural study.
AB  - Although large international studies have found consistent patterns of sex
      differences in personality traits among adults (i.e., women scoring higher on
      most facets), less is known about cross-cultural sex differences in adolescent
      personality and the role of culture and age in shaping them. The present study
      examines the NEO Personality Inventory-3 (McCrae, Costa, & Martin, 2005)
      informant ratings of adolescents from 23 cultures (N = 4,850), and investigates
      culture and age as sources of variability in sex differences of adolescents'
      personality. The effect for Neuroticism (with females scoring higher than males)
      begins to take on its adult form around age 14. Girls score higher on Openness to
      Experience and Conscientiousness at all ages between 12 and 17 years. A more
      complex pattern emerges for Extraversion and Agreeableness, although by age 17,
      sex differences for these traits are highly similar to those observed in
      adulthood. Cross-sectional data suggest that (a) with advancing age, sex
      differences found in adolescents increasingly converge toward adult patterns with
      respect to both direction and magnitude; (b) girls display sex-typed personality
      traits at an earlier age than boys; and (c) the emergence of sex differences was
      similar across cultures. Practical implications of the present findings are
      discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved). 

PMID- 25603372
TI  - Toward a comprehensive understanding of executive cognitive function in implicit
      racial bias.
AB  - Although performance on laboratory-based implicit bias tasks often is interpreted
      strictly in terms of the strength of automatic associations, recent evidence
      suggests that such tasks are influenced by higher-order cognitive control
      processes, so-called executive functions (EFs). However, extant work in this area
      has been limited by failure to account for the unity and diversity of EFs, focus
      on only a single measure of bias and/or EF, and relatively small sample sizes.
      The current study sought to comprehensively model the relation between individual
      differences in EFs and the expression of racial bias in 3 commonly used
      laboratory measures. Participants (N = 485) completed a battery of EF tasks
      (Session 1) and 3 racial bias tasks (Session 2), along with numerous individual
      difference questionnaires. The main findings were as follows: (a) measures of
      implicit bias were only weakly intercorrelated; (b) EF and estimates of automatic
      processes both predicted implicit bias and also interacted, such that the
      relation between automatic processes and bias expression was reduced at higher
      levels of EF; (c) specific facets of EF were differentially associated with
      overall task performance and controlled processing estimates across different
      bias tasks; (d) EF did not moderate associations between implicit and explicit
      measures of bias; and (e) external, but not internal, motivation to control
      prejudice depended on EF to reduce bias expression. Findings are discussed in
      terms of the importance of global and specific EF abilities in determining
      expression of implicit racial bias.

PMID- 25603375
TI  - Tandem anchoring: informational and politeness effects of range offers in social
      exchange.
AB  - We examined whether and why range offers (e.g., "I want $7,200 to $7,600 for my
      car") matter in negotiations. A selective-attention account predicts that
      motivated and skeptical offer-recipients focus overwhelmingly on the attractive
      endpoint (i.e., a buyer would hear, in effect, "I want $7,200"). In contrast, we
      propose a tandem anchoring account, arguing that offer-recipients are often
      influenced by both endpoints as they judge the offer-maker's reservation price
      (i.e., bottom line) as well as how polite they believe an extreme
      (nonaccommodating) counteroffer would be. In 5 studies, featuring scripted
      negotiation scenarios and live dyadic negotiations, we find that certain range
      offers yield improved settlement terms for offer-makers without relational costs,
      whereas others may yield relationship benefits without deal costs. We clarify the
      types of range offers that evoke these benefits and identify boundaries to their
      impact, including range width and extremity. In addition, our studies reveal
      evidence consistent with 2 proposed mechanisms, one involving an informational
      effect (both endpoints of range offers can be taken as signals of an offer
      maker's reservation price) and another involving a politeness effect (range
      offers can make extreme counteroffers seem less polite). Our results have
      implications for models of negotiation behavior and outcomes and, more broadly,
      for the nature of social exchange. (PsycINFO Database Record (c) 2015 APA, all
      rights reserved). 

PMID- 25603376
TI  - Best research practices in psychology: Illustrating epistemological and pragmatic
      considerations with the case of relationship science.
AB  - In recent years, a robust movement has emerged within psychology to increase the
      evidentiary value of our science. This movement, which has analogs throughout the
      empirical sciences, is broad and diverse, but its primary emphasis has been on
      the reduction of statistical false positives. The present article addresses
      epistemological and pragmatic issues that we, as a field, must consider as we
      seek to maximize the scientific value of this movement. Regarding epistemology,
      this article contrasts the false-positives-reduction (FPR) approach with an
      alternative, the error balance (EB) approach, which argues that any serious
      consideration of optimal scientific practice must contend simultaneously with
      both false-positive and false-negative errors. Regarding pragmatics, the movement
      has devoted a great deal of attention to issues that frequently arise in
      laboratory experiments and one-shot survey studies, but it has devoted less
      attention to issues that frequently arise in intensive and/or longitudinal
      studies. We illustrate these epistemological and pragmatic considerations with
      the case of relationship science, one of the many research domains that
      frequently employ intensive and/or longitudinal methods. Specifically, we examine
      6 research prescriptions that can help to reduce false-positive rates:
      preregistration, prepublication sharing of materials, postpublication sharing of
      data, close replication, avoiding piecemeal publication, and increasing sample
      size. For each, we offer concrete guidance not only regarding how researchers can
      improve their research practices and balance the risk of false-positive and false
      negative errors, but also how the movement can capitalize upon insights from
      research practices within relationship science to make the movement stronger and
      more inclusive.

PMID- 25603377
TI  - Dads doing diapers: Individual and relational outcomes associated with the
      division of childcare across the transition to parenthood.
AB  - This longitudinal study examined how relative contributions to the division of
      childcare are related to individual and relational outcomes across the first 2
      years of the transition to parenthood. Data were collected from a large sample of
      first-time parents 6 weeks before the birth of their child and then at 6, 12, 18,
      and 24 months postpartum. The results revealed that certain individual
      differences-especially gender and attachment avoidance-shape individual reactions
      to childcare, above and beyond the proportion of childcare tasks that partners
      report completing. Women and less avoidantly attached new parents handle the
      introduction of childcare tasks better than most men, especially those who are
      more avoidantly attached. In addition, certain reactions to childcare, such as
      childcare self-efficacy and perceptions of work-family conflict, moderate the
      relation between contributions to childcare and relationship satisfaction over
      the course of the transition. We also discuss the need for more research on men's
      adjustment during this particularly stressful transition.

PMID- 25603378
TI  - Testing the lexical hypothesis: are socially important traits more densely
      reflected in the English lexicon?
AB  - Using a set of 498 English words identified by Saucier (1997) as common person
      descriptor adjectives or trait terms, I tested 3 instantiations of the lexical
      hypothesis, which posit that more socially important person descriptors show
      greater density in the lexicon. Specifically, I explored whether trait terms that
      have greater relational impact (i.e., more greatly influence how others respond
      to a person) have more synonyms, are more frequently used, and are more strongly
      correlated with other trait terms. I found little evidence to suggest that trait
      terms rated as having greater relational impact were more frequently used or had
      more synonyms. However, these terms correlated more strongly with other trait
      terms in the set. Conversely, a trait term's loadings on structural factors
      (e.g., the Big Five, HEXACO) were extremely good predictors of the term's
      relational impact. The findings suggest that the lexical hypothesis may not be
      strongly supported in some ways it is commonly understood but is supported in the
      manner most important to investigations of trait structure. Specifically, trait
      terms with greater relational impact tend to more strongly correlate with other
      terms in lexical sets and thus have a greater role in driving the location of
      factors in analyses of trait structure. Implications for understanding the
      meaning of lexical factors such as the Big Five are discussed.

PMID- 25603380
TI  - This too shall pass: temporal distance and the regulation of emotional distress.
AB  - Does the temporal perspective people adopt when reflecting on negative events
      influence how they respond emotionally to these events? If so, through what
      cognitive pathway(s) does it have this effect? Seven studies explored these
      questions. Studies 1a, 1b, and 2 tested our basic hypothesis that adopting a
      distant-future perspective on recent stressors (relative to a near-future or
      control perspective) reduces emotional distress, examining 4 potential mediators
      of this effect. Study 3 built upon the prior studies by investigating whether
      their findings apply to a new domain and affect longer-term outcomes. Studies 4-6
      centered on a key cognitive mechanism that helped to account for the distress
      reducing properties of temporal distancing across our first 4 studies
      impermanence focus. Studies 4 and 5 examined whether individual differences in
      impermanence focus predicted emotional reactions to negative events in a manner
      similar to adopting a distant-future perspective. They also explored the
      implications of impermanence focus for broader academic (Study 4) and
      psychological (Study 5) functioning. Finally, Study 6 manipulated impermanence
      focus to test whether it affected emotional reactions to stressors in a manner
      parallel to adopting a distant-future perspective. Together, these findings
      demonstrate that temporal distancing plays an important role in emotional coping
      with negative events, and that it does so by directing individuals' attention to
      the impermanent aspects of these events. (PsycINFO Database Record (c) 2015 APA,
      all rights reserved). 

PMID- 25603381
TI  - High-resolution millimeter wave spectroscopy and ab initio calculations of
      aminomalononitrile.
AB  - The HCN trimer aminomalononitrile (H2NCH(CN)2, AMN) is considered as a key
      compound in prebiotic chemistry and a potential candidate for detection in the
      interstellar medium. In this view, we studied the rotational spectrum of AMN in
      the 120-245 GHz frequency range. The spectroscopic work was augmented by high
      level ab initio calculations. The calculations showed that between two existing
      rotamers, symmetric and asymmetric, the most stable is the asymmetric
      conformation, and it is the only conformation observed in the recorded spectra.
      The symmetric conformation is 6.7 kJ/mol higher in energy and thus has a very low
      Boltzmann factor. The analysis of the rotational spectra of the A conformation
      has shown that the observed lines exhibit a doublet or quartet structure owing to
      two large-amplitude motions, C-N torsion and amino group inversion. To study the
      large-amplitude motions in detail, we calculated a two-dimensional potential
      energy surface and determined the barrier heights for the torsion and inversion,
      Vt = 12.5 kJ/mol and Vi = 19.1 kJ/mol. About 2500 assigned rotational transitions
      in the ground vibrational state were fitted within experimental accuracy using
      the reduced axes system Hamiltonian. The set of obtained spectroscopic parameters
      allows accurate calculation of transition frequencies and intensities for an
      astrophysical search of AMN. 

PMID- 25603379
TI  - Mental simulation and meaning in life.
AB  - Mental simulation, the process of self-projection into alternate temporal,
      spatial, social, or hypothetical realities is a distinctively human capacity.
      Numerous lines of research also suggest that the tendency for mental simulation
      is associated with enhanced meaning. The present research tests this association
      specifically examining the relationship between two forms of simulation (temporal
      and spatial) and meaning in life. Study 1 uses neuroimaging to demonstrate that
      enhanced connectivity in the medial temporal lobe network, a subnetwork of the
      brain's default network implicated in prospection and retrospection, correlates
      with self-reported meaning in life. Study 2 demonstrates that experimentally
      inducing people to think about the past or future versus the present enhances
      self-reported meaning in life, through the generation of more meaningful events.
      Study 3 demonstrates that experimentally inducing people to think specifically
      versus generally about the past or future enhances self-reported meaning in life.
      Study 4 turns to spatial simulation to demonstrate that experimentally inducing
      people to think specifically about an alternate spatial location (from the
      present location) increases meaning derived from this simulation compared to
      thinking generally about another location or specifically about one's present
      location. Study 5 demonstrates that experimentally inducing people to think about
      an alternate spatial location versus one's present location enhances meaning in
      life, through meaning derived from this simulation. Study 6 demonstrates that
      simply asking people to imagine completing a measure of meaning in life in an
      alternate location compared with asking them to do so in their present location
      enhances reports of meaning. This research sheds light on an important
      determinant of meaning in life and suggests that undirected mental simulation
      benefits psychological well-being.

PMID- 25603382
TI  - R-Smad signaling-mediated VEGF expression coordinately regulates endothelial cell
      differentiation of rat mesenchymal stem cells.
AB  - A low-efficiency yield hinders the use of stem cells as a source of endothelial
      cells (ECs) for therapeutic vascularization, and the diversity of the
      transforming growth factor-beta (TGF-beta) superfamily has undermined
      understanding the effects of its potent vascularization-inducing. Herein, we
      studied the role of the TGF-beta superfamily in EC differentiation of rat bone
      marrow mesenchymal stem cells (MSCs) induced by Smad2/3 and Smad1/5/8 signaling.
      MSCs that had been sorted by flow cytometry as CD31-negative were cultured for 14
      days in medium supplemented with vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) as the control. The Smad2/3 pathway was
      activated by TGF-beta1 and Smad1/5/8 by bone morphogenetic proteins (BMPs). In
      the early phase in the Smad2/3-activated group, there were 10% CD31-positive
      cells, which was significantly higher than in the control group. A low Smad1/5/8
      phosphorylation level after BMP4 activation doubled the number of CD31-positive
      cells, while a higher phosphorylation level after BMP9 activation showed no
      effect. A Smad2/3 inhibitor initially blocked differentiation but later promoted
      it, while a Smad1/5/8 inhibitor reversed the induction observed with BMPs.
      Moreover, the positive effects of R-Smad on differentiation were weakened by the
      VEGF neutralizing antibody, and a Smad3 inhibitor decreased VEGF expression and
      blocked differentiation in both the early and late phases. In conclusion,
      differentiation of ECs from MSCs via Smad2/3 signaling is stage dependent.
      Activation, particularly by Smad3, significantly promotes differentiation at an
      early phase but later is suppressive. A low Smad1/5/8 phosphorylation level has a
      positive effect, and R-Smad effects are partly mediated by VEGF. 

PMID- 25603384
TI  - Influence of total intravenous anaesthesia and isoflurane on plasma interleukin
      concentrations after colorectal cancer surgery.

PMID- 25603383
TI  - Sleep complaints in adolescent depression: one year naturalistic follow-up study.
AB  - BACKGROUND: Sleep complaints are highly prevalent in adolescents suffering from
      major depressive disorder (MDD). The aims of this study were to describe the
      longitudinal course of sleep complaints, and to assess the association between
      sleep complaints and clinical outcome in a sample of adolescents with MDD during
      naturalistic follow-up. METHODS: A sample of adolescent outpatients (n = 166; age
      13-19 years, 17.5% boys) diagnosed with MDD was followed-up during one year in
      naturalistic settings. Sleep symptoms and psychiatric symptoms were assessed with
      interviews and self-report questionnaires. RESULTS: All sleep complaints were
      less frequent at one-year follow-up compared to baseline. Baseline sleep
      complaints did not adversely affect clinical outcome at one-year follow-up:
      severity of the sleep complaints at baseline was associated with a steeper
      improvement of depressive and anxiety symptoms, suicidality/self-harm symptoms,
      and overall psychosocial functioning over time. CONCLUSIONS: Our results suggest
      that sleep disturbances at baseline do not necessarily lead to poorer clinical
      outcome during follow-up. Larger longitudinal studies combining both subjective
      and objective measures of sleep in depressed adolescents are needed to clarify
      the link between sleep and depression further.

PMID- 25603385
TI  - The kalaemic and neuromuscular effects of succinylcholine in centronuclear
      myopathy: A pilot investigation in a canine model.
AB  - BACKGROUND: Myopathies are generally considered to increase the risk for
      succinylcholine-induced hyperkalaemia and may affect the duration of action of
      neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital
      and produces various degrees of muscular weakness and associated complications
      such as respiratory failure. The effects of succinylcholine and the potentially
      lethal consequences of hyperkalaemia on patients with CNM are unknown due to its
      rarity. One source of information is the dog, as CNM occurs naturally in dogs.
      Because of its remarkable similarity with the disease in man, canine CNM can
      serve as a model to further our knowledge of the effects of succinylcholine.
      OBJECTIVES: We examined the kalaemic and neuromuscular effects of succinylcholine
      in dogs with and without autosomal-recessive CNM. DESIGN: A prospective,
      experimental study. SETTING: Anaesthesiology laboratory, College of Veterinary
      Medicine, Cornell University, New York, USA. PATIENTS: Six dogs with autosomal
      recessive CNM and six control dogs. INTERVENTIONS: Dogs received succinylcholine
      0.3 mg kg during isoflurane anaesthesia. MAIN OUTCOME MEASURES: Whole blood
      potassium concentration was measured 5 min before and after succinylcholine
      administration. Neuromuscular function was measured with acceleromyography and
      single twitch stimulation. RESULTS: All dogs recovered uneventfully from
      anaesthesia. The increase in potassium concentration [mean (SD)] following
      succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l and control 0.7
      (0.4) mmol l (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was
      longer in the CNM group (all P < 0.001); 90% recovery took 35.5 (1.18) min for
      the CNM group and 23.3 (1.68) min for the control group. CONCLUSION: CNM did not
      exacerbate the increase in blood potassium that is ordinarily seen with
      succinylcholine. Recovery from succinylcholine was nearly 50% longer in dogs with
      CNM. Although our sample size is too small to evaluate the incidence of
      succinylcholine-induced hyperkalaemia, extrapolation of these findings suggests
      that increased duration of action should be expected if succinylcholine is given
      to a patient with autosomal-recessive CNM.

PMID- 25603386
TI  - Early recognition of cardiac tamponade using cerebral oximetry during ventricular
      tachycardia ablation.

PMID- 25603387
TI  - Adjusting tracheal tube cuff pressure.

PMID- 25603388
TI  - Epidural catheter removal for initiation of emergency anticoagulant therapy in
      acute coronary syndrome--when is the time right?

PMID- 25603389
TI  - Dose-dependency of dexamethasone on the analgesic effect of interscalene block
      for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled
      trial.
AB  - BACKGROUND: Dexamethasone prolongs the duration of single-shot interscalene
      brachial plexus block (SISB). However, dose-dependency of dexamethasone as an
      adjuvant for SISB remains insufficiently understood. OBJECTIVE: The objective of
      this study is to evaluate the effect of different doses of dexamethasone on the
      duration of SISB using ropivacaine 0.5%. DESIGN: A randomised, double-blind
      controlled trial. SETTING: Single university tertiary care centre. PATIENTS: One
      hundred and forty-four patients scheduled for elective arthroscopic shoulder
      surgery were allocated randomly to one of four groups. INTERVENTIONS: Patients
      received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing
      dexamethasone 2.5, 5.0 or 7.5 mg for SISB. MAIN OUTCOME MEASURES: The primary
      endpoint was the time to the first analgesic request. Pain scores and adverse
      effects were also assessed up to 48 h postoperatively. RESULTS: Inclusion of
      dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases
      in time to the first analgesic request by factors of 1.6, 2.2 and 1.8,
      respectively. The percentages of patients not requiring analgesics in the first
      48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39
      and 33%, respectively (P < 0.001). There were no significant effects on pain
      scores or incidences of adverse effects. CONCLUSION: Dexamethasone demonstrated
      significant beneficial dose-dependent effects on duration to the first analgesic
      request, the number of patients not requiring analgesics and analgesic use in the
      first 48 h after SISB for arthroscopic shoulder surgery. There were no
      significant effects on pain scores or incidences of adverse effects. TRIAL
      REGISTRATION: the trial was registered with the Clinical Trial Registry of Korea:
      https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

PMID- 25603390
TI  - Reply to: Influence of total intravenous anaesthesia and isoflurane on plasma
      interleukin concentrations after colorectal cancer surgery.

PMID- 25603391
TI  - Reply to: Intra-arterial injection; timely and proper treatment can make all the
      difference.

PMID- 25603393
TI  - Influence of texture coefficient on surface morphology and sensing properties of
      W-doped nanocrystalline tin oxide thin films.
AB  - For the first time, a new facile approach based on simple and inexpensive
      chemical spray pyrolysis (CSP) technique is used to deposit Tungsten (W) doped
      nanocrystalline SnO2 thin films. The textural, optical, structural and sensing
      properties are investigated by GAXRD, UV spectroscopy, FESEM, AFM, and home-built
      sensing setup. The gas sensing results indicate that, as compared to pure SnO2, 1
      wt % W-doping improves sensitivity along with better response (<2 s) and recovery
      time (<25 s) toward NO2 gas at operating temperatures of ~225  degrees C. The
      optimal composition of 1 wt % W-doped films exhibit lowest crystallite size of
      the order of ~8-10 nm with reduced energy band gap and large roughness values of
      3.82 eV and 3.01 nm, respectively. Reduction in texture coefficient along highly
      dense (110) planes with concomitant increase along loosely packed (200) planes is
      found to have prominent effect on gas sensing properties of W-doped films. 

PMID- 25603394
TI  - Alnus peptides modify membrane porosity and induce the release of nitrogen-rich
      metabolites from nitrogen-fixing Frankia.
AB  - Actinorhizal plant growth in pioneer ecosystems depends on the symbiosis with the
      nitrogen-fixing actinobacterium Frankia cells that are housed in special root
      organs called nodules. Nitrogen fixation occurs in differentiated Frankia cells
      known as vesicles. Vesicles lack a pathway for assimilating ammonia beyond the
      glutamine stage and are supposed to transfer reduced nitrogen to the plant host
      cells. However, a mechanism for the transfer of nitrogen-fixation products to the
      plant cells remains elusive. Here, new elements for this metabolic exchange are
      described. We show that Alnus glutinosa nodules express defensin-like peptides,
      and one of these, Ag5, was found to target Frankia vesicles. In vitro and in vivo
      analyses showed that Ag5 induces drastic physiological changes in Frankia,
      including an increased permeability of vesicle membranes. A significant release
      of nitrogen-containing metabolites, mainly glutamine and glutamate, was found in
      N2-fixing cultures treated with Ag5. This work demonstrates that the Ag5 peptide
      is central for Frankia physiology in nodules and uncovers a novel cellular
      function for this large and widespread defensin peptide family. 

PMID- 25603395
TI  - Recent radiation in a marine and freshwater dinoflagellate species flock.
AB  - Processes of rapid radiation among unicellular eukaryotes are much less studied
      than among multicellular organisms. We have investigated a lineage of cold-water
      microeukaryotes (protists) that appear to have diverged recently. This lineage
      stands in stark contrast to known examples of phylogenetically closely related
      protists, in which genetic difference is typically larger than morphological
      differences. We found that the group not only consists of the marine-brackish
      dinoflagellate species Scrippsiella hangoei and the freshwater species Peridinium
      aciculiferum as discovered previously but also of a whole species flock. The
      additional species include Peridinium euryceps and Peridinium baicalense, which
      are restricted to a few lakes, in particular to the ancient Lake Baikal, Russia,
      and freshwater S. hangoei from Lake Baikal. These species are characterized by
      relatively large conspicuous morphological differences, which have given rise to
      the different species descriptions. However, our scanning electron microscopic
      studies indicate that they belong to a single genus according to traditional
      morphological characterization of dinoflagellates (thecal plate patterns).
      Moreover, we found that they have identical SSU (small subunit) rDNA fragments
      and distinct but very small differences in the DNA markers LSU (large subunit)
      rDNA, ITS2 (internal transcribed spacer 2) and COB (cytochrome b) gene, which are
      used to delineate dinoflagellates species. As some of the species co-occur, and
      all four have small but species-specific sequence differences, we suggest that
      these taxa are not a case of phenotypic plasticity but originated via recent
      adaptive radiation. We propose that this is the first clear example among free
      living microeukaryotes of recent rapid diversification into several species
      followed by dispersion to environments with different ecological conditions. 

PMID- 25603397
TI  - Hairy Core-Shell Polymer Nano-objects from Self-Assembled Block Copolymer
      Structures.
AB  - Fabrication of core-shell polymer nano-objects with well-defined shape and hairy
      shell has been a subject of immense interest in polymer chemistry for more than
      two decades now. Different approaches such as those involving synthesis (grafting
      approaches) and block copolymer self-assembly (solution as well as bulk) have
      been used for the preparation of such nano-objects. Of these approaches that
      involving bulk self-assembled structures of block copolymers have been of special
      interest because of the simplicity and range of shape and structures possible.
      The present review focuses on the advances which have been made in this direction
      using diblock and triblock self-assembled structures. It will be shown that this
      approach allows to fabricate hairy nano-objects of not only simple shapes such as
      spheres, rods, and sheets but also those with more complex shape and morphology
      such as multicompartment micelles, which are not possible to obtain with
      synthetic or solution self-assembly approaches. Furthermore, interesting
      structures such as Janus nano-objects could also be fabricated using this
      approach. The review further highlights the use of such nano-objects for
      templating applications. 

PMID- 25603396
TI  - Extracellular matrix structure governs invasion resistance in bacterial biofilms.
AB  - Many bacteria are highly adapted for life in communities, or biofilms. A defining
      feature of biofilms is the production of extracellular matrix that binds cells
      together. The biofilm matrix provides numerous fitness benefits, including
      protection from environmental stresses and enhanced nutrient availability. Here
      we investigate defense against biofilm invasion using the model bacterium Vibrio
      cholerae. We demonstrate that immotile cells, including those identical to the
      biofilm resident strain, are completely excluded from entry into resident
      biofilms. Motile cells can colonize and grow on the biofilm exterior, but are
      readily removed by shear forces. Protection from invasion into the biofilm
      interior is mediated by the secreted protein RbmA, which binds mother-daughter
      cell pairs to each other and to polysaccharide components of the matrix. RbmA,
      and the invasion protection it confers, strongly localize to the cell lineages
      that produce it. 

PMID- 25603398
TI  - Finite element analysis of mechanics of neovessels with intraplaque hemorrhage in
      carotid atherosclerosis.
AB  - BACKGROUND: Intraplaque hemorrhage is a widely known factor facilitating plaque
      instability. Neovascularization of plaque can be regarded as a compensatory
      response to the blood supply in the deep intimal and medial areas of the artery.
      Due to the physiological function, the deformation of carotid atherosclerotic
      plaque would happen under the action of blood pressure and blood flow. Neovessels
      are subject to mechanical loading and likely undergo deformation. The rupture of
      neovessels may deteriorate the instability of plaque. This study focuses on the
      local mechanical environments around neovessels and investigates the relationship
      between the biomechanics and the morphological specificity of neovessels.
      METHODS: Stress and stretch were used to evaluate the rupture risk of the
      neovessels in plaque. Computational structural analysis was performed based on
      two human carotid plaque slice samples. Two-dimensional models containing
      neovessels and other components were built according to the plaque slice samples.
      Each component was assumed to be non-linear isotropic, piecewise homogeneous and
      incompressible. Different mechanical boundary conditions, i.e. static pressures,
      were imposed in the carotid lumen and neovessels lumen respectively. Finite
      element method was used to simulate the mechanical conditions in the
      atherosclerotic plaque. RESULTS: Those neovessels closer to the carotid lumen
      undergo larger stress and stretch. With the same distance to the carotid lumen,
      the longer the perimeter of neovessels is, the larger stress and the deformation
      of the neovessels will be. Under the same conditions, the neovessels with larger
      curvature suffer greater stress and stretch. Neovessels surrounded by red blood
      cells undergo a much larger stretch. CONCLUSIONS: Local mechanical conditions may
      result in the hemorrhage of neovessels and accelerate the rupture of plaque. The
      mechanical environments of the neovessel are related to its shape, curvature,
      distance to the carotid lumen and the material properties of plaque.

PMID- 25603399
TI  - A simple electrochemical biosensor for highly sensitive and specific detection of
      microRNA based on mismatched catalytic hairpin assembly.
AB  - MicroRNAs (miRNAs) play vital regulatory roles in cancer development and a
      variety of diseases, which make them become promising biomarkers. Here, a simple
      electrochemical biosensor was developed for highly sensitive and specific
      detection of target miRNA using mismatched catalytic hairpin assembly (CHA). The
      target miRNA triggered the toehold strand displacement assembly of two hairpin
      substrates, which led to the cyclic reuse of the target miRNA and the CHA
      products. Compared with the traditional CHA, mismatched CHA could decrease the
      nonspecific CHA products, which reduced the background signal significantly.
      Under the optimal experimental conditions and using differential pulse
      voltammetry, the established biosensor could detect target miRNA down to 0.6 pM
      (S/N=3) with a linear range from 1 pM to 25 nM, and discriminate target miRNA
      from mismatched miRNA with a high selectivity. It was also applied to the
      determination of miRNA spiked into human total RNA samples. Thus, this biosensing
      strategy might become a potential alternative tool for detection of miRNA in
      biomedical research and early clinical diagnosis.

PMID- 25603400
TI  - Magnetically optimized SERS assay for rapid detection of trace drug-related
      biomarkers in saliva and fingerprints.
AB  - New developments in the fields of human healthcare and social security call for
      the exploration of an easy and on-field method to detect drug-related biomarkers.
      In this paper, Au nanoparticles dotted magnetic nanocomposites (AMN) modified
      with inositol hexakisphosphate (IP6) were used as surface-enhanced Raman
      scattering (SERS) substrate to quickly monitor trace drug-related biomarkers in
      saliva and to on-site screen a trace drug biomarker in fingerprints. Due to
      inducing with an external magnet, such substrate presented a huge SERS activity,
      which has met the sensitivity requirement for assay to detect the drug biomarkers
      in saliva from the U.S. Substance Abuse and Mental Health Services
      Administration, and also the limit of detection for drug biomarker in fingerprint
      reached 100 nM. In addition, this AMN-based SERS assay was successfully conducted
      using a portable Raman spectrometer, which could be used to on-site and
      accurately differentiate between the smokers and drug addicts in near future.

PMID- 25603401
TI  - Real-time electrochemical detection of hydrogen peroxide secretion in live cells
      by Pt nanoparticles decorated graphene-carbon nanotube hybrid paper electrode.
AB  - In this work, we develop a new type of flexible and lightweight electrode based
      on highly dense Pt nanoparticles decorated free-standing graphene-carbon nanotube
      (CNT) hybrid paper (Pt/graphene-CNT paper), and explore its practical application
      as flexible electrochemical biosensor for the real-time tracking hydrogen
      peroxide (H2O2) secretion by live cells. For the fabrication of flexible
      nanohybrid electrode, the incorporation of CNT in graphene paper not only
      improves the electrical conductivity and the mechanical strength of graphene
      paper, but also increases its surface roughness and provides more nucleation
      sites for metal nanoparticles. Ultrafine Pt nanoparticles are further decorated
      on graphene-CNT paper by well controlled sputter deposition method, which offers
      several advantages such as defined particle size and dispersion, high loading
      density and strong adhesion between the nanoparticles and the substrate.
      Consequently, the resultant flexible Pt/graphene-CNT paper electrode demonstrates
      a variety of desirable electrochemical properties including large electrochemical
      active surface area, excellent electrocatalytic activity, high stability and
      exceptional flexibility. When used for nonenzymatic detection of H2O2,
      Pt/graphene-CNT paper exhibits outstanding sensing performance such as high
      sensitivity, selectivity, stability and reproducibility. The sensitivity is 1.41
      uA uM(-1) cm(-2) with a linear range up to 25 uM and a low detection limit of 10
      nM (S/N=3), which enables the resultant biosensor for the real-time tracking H2O2
      secretion by live cells macrophages.

PMID- 25603402
TI  - The small bowel microbiota.
AB  - PURPOSE OF REVIEW: Although many studies of the microbiota have been specific to
      the colonic or faecal microbiota, several studies are relevant to or directly
      address the small bowel microbiota in health and disease. A selection of recent
      landmark findings is addressed here. RECENT FINDINGS: The complexity of host
      microbe interactions is confirmed by unfolding evidence for signalling networks
      including microbe-macrophage-neuronal communication and several examples of diet
      microbe-host metabolic exchanges. The contribution of the microbiota to several
      disorders, including celiac disease and inflammatory bowel disease, is
      increasingly evident and the importance of drug-bug interactions has been
      clarified. SUMMARY: Despite difficulty accessing the small bowel microbiota,
      there is growing evidence for its role in development, homeostasis and a
      diversity of diseases.

PMID- 25603403
TI  - The intestinal epithelial cell cycle: uncovering its 'cryptic' nature.
AB  - PURPOSE OF REVIEW: To discuss the recent landmark findings that have increased
      our understanding not only of the role of the epithelial cell cycle in the
      homeostasis of the small intestine, but also its relevance to inflammation and
      cancer. RECENT FINDINGS: Recent data have unveiled novel information on protein
      interactions directly involved in the cell cycle as well as in the pathways that
      transduce external environmental signals to the cell cycle. A growing body of the
      recent evidence confirms the importance of food as well as hormonal regulation in
      the gut on cell cycle. Information on the contribution of the epithelial
      microenvironment, including the microbiota, has grown substantially in the recent
      years as well as on the gene-environment interactions and the multiple epigenetic
      mechanisms involved in regulating cell-cycle proteins and signalling. Finally,
      further studies investigating the dysregulation of the cell cycle during
      inflammation and proliferation have increased our understanding of the
      pathophysiology of chronic inflammatory diseases and cancer. SUMMARY: This review
      highlights some of the most recent advances that further emphasize the importance
      of the cell cycle in the small intestine during homeostasis as well as in
      inflammation and cancer.

PMID- 25603404
TI  - Chronic infections of the small intestine.
AB  - PURPOSE OF REVIEW: Chronic infections of the small intestine cause significant
      morbidity and mortality globally. This review focuses on the recent advances in
      the field of our understanding of selected intestinal infections. RECENT
      FINDINGS: Primary and secondary immunodeficiency increase the susceptibility to
      many chronic intestinal infections. Endoscopy and intestinal biopsies are central
      to establishing a diagnosis of these conditions. Tuberculosis (TB) remains a
      major global health challenge. Emerging therapeutic agents to counteract
      multidrug-resistant strains have shown clinical efficacy, but concerns regarding
      mortality remain. PCR-based diagnostic TB tests have the potential to reduce
      diagnostic delays, but remain to be validated for intestinal infections.
      Adjunctive diagnostic imaging modalities can differentiate infections from
      Crohn's disease with increasing accuracy. Whipple's disease remains rare, but
      there have been substantial advances in our understanding of the causative
      organism Tropheryma whipplei. Extended treatment with broad-spectrum antibiotics
      is effective in most cases. The narrow therapeutic window and limited
      armamentarium for treating invasive filamentous fungal infections contribute to
      their significant morbidity and high rates of mortality. SUMMARY: The speed and
      accuracy of diagnosing chronic intestinal infections have improved with recent
      imaging and laboratory methodologies. Significant research opportunities remain
      for clinicians and scientists to improve the diagnostic accuracy and clinical
      outcomes of chronic intestinal infections.

PMID- 25603405
TI  - Super-resolution in label-free photomodulated reflectivity.
AB  - We demonstrate a new, label-free, far-field super-resolution method based on an
      ultrafast pump-probe scheme oriented toward nanomaterial imaging. A focused pump
      laser excites a diffraction-limited spatial temperature profile, and the
      nonlinear changes in reflectance are probed. Enhanced spatial resolution is
      demonstrated with nanofabricated silicon and vanadium dioxide nanostructures.
      Using an air objective, resolution of 105 nm was achieved, well beyond the
      diffraction limit for the pump and probe beams and offering a novel kind of
      dedicated nanoscopy for materials. 

PMID- 25603406
TI  - A fast semi-quantitative LC-MS method for measurement of intact apolipoprotein A
      I reveals novel proteoforms in serum.
AB  - BACKGROUND: Surrogate markers for reverse cholesterol transport (RCT) efficiency
      such as HDL cholesterol and immune methods for apolipoprotein A-I (ApoA-I) may
      not fully reflect the actual efficiency of the RCT pathway. Several genetic
      variants and different posttranslational proteoforms of ApoA-I may unevenly
      affect the functionality of the HDL particle to efflux cholesterol. A method
      employing top-down immunoaffinity LC-MS of ApoA-I in order to characterize the
      most prevalent ApoA-I proteoforms in human plasma is described. METHODS: Diluted
      plasma was directly injected into a 2D LC-MS system consisting of an affinity
      column and an analytical column. Enriched ApoA-I fractions were introduced into
      the MS and intact or fragmented ApoA-I was analyzed. RESULTS: ApoA-I as detected
      by the described LC-MS method distributes into at least 14 major potential
      proteoforms exceeding detection limit in human plasma. Substantial amounts of
      ApoA-I in plasma were found to occur as truncated, oxidized, glycated and
      glycosylated proteoforms. Levels of glycated ApoA-I distinguished significantly
      diabetic from non-diabetic samples. In addition novel truncated and glycosylated
      proteoforms were detected. CONCLUSIONS: ApoA-I proteoforms measured by LC-MS
      represent a useful approach to augment the clinical picture of ApoA-I and its
      function in health and disease.

PMID- 25603407
TI  - Relationship between carotid artery intima-media thickness and small dense low
      density lipoprotein cholesterol concentrations measured by homogenous assay in
      Japanese subjects.
AB  - BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C)
      concentrations correlate more strongly with coronary heart disease than other LDL
      C and large LDL particle concentrations. We investigated the association between
      carotid artery intima-media thickness (IMT) and sdLDL-C concentrations in
      Japanese subjects. METHODS: Carotid artery IMT, blood pressure (BP), fasting
      plasma sdLDL-C, glucose metabolism, lipid, and C-reactive protein concentrations
      were measured in 97 native Japanese subjects. Carotid artery IMT was assessed by
      ultrasonography, and sdLDL-C concentrations were measured by a homogenous assay.
      Pearson's correlation coefficient analyses and multiple regression analyses were
      used to examine the relationships between carotid artery IMT values, sdLDL-C
      values, and other clinical variables. RESULTS: After multiple regression
      analysis, including age, sex, body mass index, systolic BP, diastolic BP, fasting
      plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR), total-C, high
      density lipoprotein (HDL)-C, triglyceride, LDL-C, non-HDL-C, large buoyant LDL-C,
      and sdLDL-C, carotid artery IMT remained significantly associated with age,
      systolic BP, diastolic BP, and sdLDL-C, whereas sdLDL-C remained significantly
      associated with age, total-C, HDL-C, triglycerides, and carotid artery IMT.
      CONCLUSIONS: When measured by a homogenous assay, carotid artery IMT may have a
      closer relationship with sdLDL-C concentrations than other lipid parameters in
      Japanese subjects. sdLDL-C may be a potentially useful risk marker when assessing
      carotid artery IMT in Japanese subjects.

PMID- 25603408
TI  - Matrix and bilirubin interference for high-sensitivity cardiac troponin I.

PMID- 25603409
TI  - Would You Want to Be the Patient? "Live Surgical Broadcast" or "As-Live Unedited
      Surgical Broadcast".
AB  - OBJECTIVE: To evaluate patient safety, educational value, and ethical issues
      surrounding "Live surgical broadcast" (LSB) and "As-live surgical broadcast"
      (ALB) using data obtained from urologic delegates attending two recent
      endourology meetings in the United Kingdom. SUBJECTS AND METHODS: Two hundred
      twelve delegates at the UK section meeting of the Societe Internationale
      d'Urologie (SIU) were invited to complete an online survey using
      SurveyMonkey((r)) to compare their previous perceptions of LSB and ALB, and to
      compare their current experience of ALB to previous experience of LSB. One
      hundred three delegates at the British Association of Urological Surgeons (BAUS)
      Endourology meeting used live voting keypads to compare their experience of LSB
      and ALB simultaneously, as well as comparing their current experience of ALB to
      previous experience of LSB. Responses were recorded using a Likert scale.
      RESULTS: One hundred sixty-five responses were analyzed from the meetings. Most
      delegates were in specialist practice as a consultant or trainee (89.1%). LSB had
      been witnessed more than ALB (87.1% vs 66.6%, p=0.049). Based on previous
      experiences, the educational value of both formats was felt similar, but
      delegates felt there were significant patient safety benefits with ALB over LSB.
      Delegates were significantly less likely to recommend a friend or family, or
      volunteer themselves to be a patient in an LSB setting. On-the-day comparison of
      LSB and ALB shows a similar educational value to both formats, but with
      significantly less concern for the surgeon and patient's outcome with ALB.
      CONCLUSION: ALB offers similar educational opportunities to delegates when
      compared with LSB, while appearing to offer significant welfare benefits to both
      surgeon and patient. Further studies are required to objectively quantify these
      subjective observations.

PMID- 25603411
TI  - Edge-on gating effect in molecular wires.
AB  - This work demonstrates edge-on chemical gating effect in molecular wires
      utilizing the pyridinoparacyclophane (PC) moiety as the gate. Different
      substituents with varied electronic demands are attached to the gate to simulate
      the effect of varying gating voltages similar to that in field-effect transistor
      (FET). It was observed that the orbital energy level and charge carrier's
      tunneling barriers can be tuned by changing the gating group from strong electron
      acceptors to strong electron donors. The single molecule conductance and current
      voltage characteristics of this molecular system are truly similar to those
      expected for an actual single molecular transistor. 

PMID- 25603410
TI  - Inhibition of bone morphogenetic protein signal transduction prevents the medial
      vascular calcification associated with matrix Gla protein deficiency.
AB  - OBJECTIVE: Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic
      protein (BMP) signal transduction. MGP deficiency is associated with medial
      calcification of the arterial wall, in a process that involves both osteogenic
      transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal
      transition of endothelial cells (EndMT). In this study, we investigated the
      contribution of BMP signal transduction to the medial calcification that develops
      in MGP-deficient mice. APPROACH AND RESULTS: MGP-deficient mice (MGP(-/-)) were
      treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc,
      beginning one day after birth. Aortic calcification was assessed in 28-day-old
      mice by measuring the uptake of a fluorescent bisphosphonate probe and by
      staining tissue sections with Alizarin red. Aortic calcification was 80% less in
      MGP(-/-) mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated
      control animals (P<0.001 for both). LDN-193189-treated MGP(-/-) mice survived
      longer than vehicle-treated MGP(-/-) mice. Levels of phosphorylated Smad1/5 and
      Id1 mRNA (markers of BMP signaling) did not differ in the aortas from MGP(-/-)
      and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP(-/-)
      aortas, an effect that was prevented by LDN-193189. Calcification of isolated
      VSMCs was also inhibited by LDN-193189. CONCLUSIONS: Inhibition of BMP signaling
      leads to reduced vascular calcification and improved survival in MGP(-/-) mice.
      The EndMT and osteogenic transdifferentiation associated with MGP deficiency is
      dependent upon BMP signaling. These results suggest that BMP signal transduction
      has critical roles in the development of vascular calcification in MGP-deficient
      mice.

PMID- 25603412
TI  - Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar
      disorder: a postmortem study on the amygdala.
AB  - Perineuronal nets (PNNs) are specialized extracellular matrix aggregates
      surrounding distinct neuronal populations and regulating synaptic functions and
      plasticity. Previous findings showed robust PNN decreases in amygdala, entorhinal
      cortex and prefrontal cortex of subjects with schizophrenia (SZ), but not bipolar
      disorder (BD). These studies were carried out using a chondroitin sulfate
      proteoglycan (CSPG) lectin marker. Here, we tested the hypothesis that the CSPG
      aggrecan, and 6-sulfated chondroitin sulfate (CS-6) chains highly represented in
      aggrecan, may contribute to these abnormalities. Antibodies against aggrecan and
      CS-6 (3B3 and CS56) were used in the amygdala of healthy control, SZ and BD
      subjects. In controls, aggrecan immunoreactivity (IR) was observed in PNNs and
      glial cells. Antibody 3B3, but not CS56, also labeled PNNs in the amygdala. In
      addition, dense clusters of CS56 and 3B3 IR encompassed CS56- and 3B3-IR glia,
      respectively. In SZ, numbers of aggrecan- and 3B3-IR PNNs were decreased,
      together with marked reductions of aggrecan-IR glial cells and CS-6 (3B3 and
      CS56)-IR 'clusters'. In BD, numbers of 3B3-IR PNNs and CS56-IR clusters were
      reduced. Our findings show disruption of multiple PNN populations in the amygdala
      of SZ and, more modestly, BD. Decreases of aggrecan-IR glia and CS-6-IR glial
      'clusters', in sharp contrast to increases of CSPG/lectin-positive glia
      previously observed, indicate that CSPG abnormalities may affect distinct glial
      cell populations and suggest a potential mechanism for PNN decreases. Together,
      these abnormalities may contribute to a destabilization of synaptic connectivity
      and regulation of neuronal functions in the amygdala of subjects with major
      psychoses. 

PMID- 25603413
TI  - Impaired regulation of emotion: neural correlates of reappraisal and distraction
      in bipolar disorder and unaffected relatives.
AB  - Deficient emotion regulation has been proposed as a crucial pathological
      mechanism in bipolar disorder (BD). We therefore investigated emotion regulation
      impairments in BD, the related neural underpinnings and their etiological
      relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder
      and 17 unaffected first-degree relatives of BD-I patients, as well as two groups
      of healthy gender-, age- and education-matched controls (N=22/17, respectively)
      were included. Participants underwent functional magnetic resonance imaging while
      applying two different emotion regulation techniques, reappraisal and
      distraction, when presented with emotional images. BD patients and relatives
      showed impaired downregulation of amygdala activity during reappraisal, but not
      during distraction, when compared with controls. This deficit was correlated with
      the habitual use of reappraisal. The negative connectivity of amygdala and
      orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed
      in BD patients and relatives. There were no significant differences between BD
      patients and relatives. As being observed in BD patients and unaffected
      relatives, deficits in emotion regulation through reappraisal may represent
      heritable neurobiological abnormalities underlying BD. The neural mechanisms
      include impaired control of amygdala reactivity to emotional stimuli and
      dysfunctional connectivity of the amygdala to regulatory control regions in the
      OFC. These are, thus, important aspects of the neurobiological basis of increased
      vulnerability for BD. 

PMID- 25603414
TI  - Analyzing the influence of BDNF heterozygosity on spatial memory response to
      17beta-estradiol.
AB  - The recent use of estrogen-based therapies as adjunctive treatments for the
      cognitive impairments of schizophrenia has produced promising results; however
      the mechanism behind estrogen-based cognitive enhancement is relatively unknown.
      Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its
      expression is highly responsive to estradiol. We recently found that estradiol
      modulates the expression of hippocampal parvalbumin-positive GABAergic
      interneurons, known to regulate neuronal synchrony and cognitive function. What
      is unknown is whether disruptions to the aforementioned estradiol-parvalbumin
      pathway alter learning and memory, and whether BDNF may mediate these events.
      Wild-type (WT) and BDNF heterozygous (+/-) mice were ovariectomized (OVX) at 5
      weeks of age and simultaneously received empty, estradiol- or progesterone-filled
      implants for 7 weeks. At young adulthood, mice were tested for spatial and
      recognition memory in the Y-maze and novel-object recognition test, respectively.
      Hippocampal protein expression of BDNF and GABAergic interneuron markers,
      including parvalbumin, were assessed. WT OVX mice show impaired performance on Y
      maze and novel-object recognition test. Estradiol replacement in OVX mice
      prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal
      origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and
      parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by
      OVX in WT mice, while E2 replacement prevented these deficits. In contrast,
      BDNF(+/-) mice showed either no response or an opposite response to hormone
      manipulation in both behavioral and molecular indices. Our data suggest that BDNF
      status is an important biomarker for predicting responsiveness to estrogenic
      compounds which have emerged as promising adjunctive therapeutics for
      schizophrenia patients. 

PMID- 25603416
TI  - C-reactive protein polymorphisms influence serum CRP-levels independent of
      disease activity in ankylosing spondylitis.
AB  - OBJECTIVES: C-reactive protein (CRP) levels are frequently used to determine
      disease activity in patients with ankylosing spondylitis (AS), but these levels
      may not reflect disease activity. We therefore investigated the influence of
      common single-nucleotide polymorphisms (SNPs) in the CRP gene on CRP levels in AS
      patients. Additionally, the relation between CRP levels and BASDAI (Bath
      Ankylosing Spondylitis Disease Activity Index) was examined. METHODS: This
      exploratory cross-sectional study included 189 Dutch AS patients. CRP SNPs
      rs2794521, rs3091244, rs1800947 and rs876538 were genotyped and haplotypes
      constructed. Linear regression analysis was used for the association between SNPs
      and CRP levels, with correction for confounders non-steroidal anti-inflammatory
      drugs use, body mass index, smoking, age, gender and disease activity (BASDAI).
      RESULTS: Only 52% of AS patients with a high disease activity (BASDAI >=4) showed
      a high CRP level (>=10mg/L), whereas the others did not. In AS patients, CRP
      levels changed with different genotypes, with genotype CA of tri-allelic (C>T>A)
      SNP rs3091244 showing higher CRP levels in comparison with genotype CC (CA: 18.6
      mg/L vs. CC: 8.3 mg/L; p=0.02). Carriers of haplotype 5 (tagged by allele A of
      rs3091244) had a higher risk to express a CRP >=10 mg/L (OR=2.9, 95%CI 1.0-8.3;
      p=0.05) when compared with non-carriers. CONCLUSIONS: In AS, patients with high
      disease activity often do not show corresponding high CRP levels. We found that
      CRP levels vary with different CRP genotype in AS patients. Carrying distinct
      genetic variants might play a role in certain AS patients who show low CRP levels
      despite high disease activity (as well as high CRP levels with low disease
      activity). This observation may be important for the interpretation of disease
      activity scores that incorporate CRP levels, like the ASDAS.

PMID- 25603415
TI  - C-reactive protein gene variants: independent association with late-life
      depression and circulating protein levels.
AB  - C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that
      is commonly elevated in depressed patients. Variants in the CRP gene that
      influence protein levels could thus be associated with depression but this has
      seldom been examined, especially in the elderly. Depression was assessed in 990
      people aged at least 65 years as part of the ESPRIT study. A clinical level of
      depression (DEP) was defined as having a score of ?16 on The Center for
      Epidemiologic Studies Depression scale or a diagnosis of current major depression
      based on the Mini-International Neuropsychiatric Interview and according to
      Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single
      nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating
      levels of high-sensitivity CRP were determined. Multivariable analyses adjusted
      for socio-demographic characteristics, smoking, ischemic pathologies, cognitive
      impairment and inflammation-related chronic pathologies. The minor alleles of
      rs1130864 and rs1417938 were associated with a decreased risk of depression in
      women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants
      were associated with serum levels in a gender-specific manner, but only rs1205
      was found to be nominally associated with both an increased risk of DEP and lower
      circulating CRP levels in women. Variants of the CRP gene thus influence
      circulating CRP levels and appear as independent susceptibility factors for late
      life depression. 

PMID- 25603417
TI  - Insomnia and self-reported infections in cancer patients: An 18-month
      longitudinal study.
AB  - OBJECTIVE: This study, conducted in cancer patients, aimed to evaluate
      longitudinally whether the presence of insomnia is associated with the occurrence
      of self-reported infections. METHOD: Patients scheduled to receive a curative
      surgery for a first diagnosis of nonmetastatic cancer were solicited on the day
      of their preoperative visit. In total, 962 cancer patients completed the Insomnia
      Interview Schedule and a clinical interview to assess infectious symptoms at 6
      time points: at the perioperative phase (baseline), as well as 2, 6, 10, 14, and
      18 months later. At each assessment, patients were categorized into the following
      3 groups: insomnia syndrome (SYN), insomnia symptoms (SX), and good sleepers
      (GS). RESULTS: The analyses revealed that SYN patients at 1 time point were at a
      significantly higher risk of reporting at least 1 infectious episode at the
      subsequent assessment (OR = 1.31, p = .04), whereas SX patients were at a
      marginally significant higher risk of reporting such episodes (OR = 1.19, p =
      .08), as compared with GS. CONCLUSIONS: Although these results need replication
      and the causality needs to be established, they suggest that insomnia may
      potentiate the risk of experiencing infections during the cancer care trajectory.
      (PsycINFO Database Record

PMID- 25603418
TI  - Childhood cognitive ability moderates later-life manifestation of type 2 diabetes
      genetic risk.
AB  - OBJECTIVE: The study investigated whether childhood cognitive ability moderates
      Type 2 diabetes polygenic risk manifestation in older age. METHOD: In 940
      relatively healthy people (mean age 69.55 +/- 0.85), we tested whether self
      reported diabetes and hemoglobin HbA1c (HbA1c) levels were predicted by diabetes
      polygenic risk, cognitive ability measured about 60 years earlier, and their
      interaction. Polygenic risk scores aggregated the small effects of up to nearly
      121,000 single-nucleotide polymorphisms (SNPs). Participants' cognitive ability
      was measured at age 11. RESULTS: Both polygenic risk and low childhood cognitive
      ability significantly predicted diabetes diagnosis. Polygenic risk interacted
      with cognitive ability (p = .02), predicting HbA1c levels more strongly in people
      with below-median cognitive ability (effect r = .21) than in people with above
      median cognitive ability (effect r = .10). The interaction term was not
      significant for self-reported diabetes (p = .34), although the genetic risk
      diabetes association showed a tendency of being stronger among those with below
      median cognitive ability. CONCLUSIONS: Higher premorbid cognitive ability may
      provide some environmental protection against the manifestation of Type 2
      diabetes genetic risk. This information may improve early identification of
      diabetes risk and inform intervention development.

PMID- 25603419
TI  - Trajectories of overweight and their association with adolescent depressive
      symptoms.
AB  - OBJECTIVE: To explore the potential for a developmental approach to reveal new
      insights into the well-documented link between weight and depressive symptoms.
      METHOD: Latent class analysis identified multiple trajectories of overweight from
      24 months to 15 years in the National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development (n = 957). Structural
      equation models then used these classes to predict depressive symptoms at age 15.
      RESULTS: Five latent classes captured continuity and change in weight from early
      childhood into middle adolescence. Controlling for current weight, stably
      overweight girls tended to have the most depressive symptoms, but popularity and
      positive image appeared to buffer against some of the risks that girls faced from
      being stably overweight or becoming overweight in early to middle childhood.
      Notably, boys' longitudinal weight patterns were not associated with their
      depressive symptoms in adolescence. CONCLUSIONS: Weight histories, controlling
      for current weight, are important for understanding the psychological experience
      of overweight, especially when such histories are considered in relation to other
      aspects of psychosocial functioning. (PsycINFO Database Record

PMID- 25603421
TI  - Preclinical and clinical evidence for stem cell therapies as treatment for
      diabetic wounds.
AB  - Diabetic wounds remain a global unsolved problem and the cost of diabetes-related
      amputations and diabetic wound treatment is approximately US$3 billion and US$9
      billion per year, respectively. Diabetic foot ulcers (DFUs) occur in 15% of all
      patients with diabetes and precede 84% of all diabetes-related lower leg
      amputations. Currently, there is no satisfying treatment for these hard-to-heal
      wounds. However, as we discuss here, experimental preclinical evidence for the
      successful use of adult stem cell therapies for diabetic wounds gives new hope
      for the development of effective treatments for use in the clinic. 

PMID- 25603420
TI  - The prospective association between positive psychological well-being and
      diabetes.
AB  - OBJECTIVE: Positive psychological well-being has protective associations with
      cardiovascular outcomes, but no studies have considered its association with
      diabetes. This study investigated links between well-being and incident diabetes.
      METHODS: At study baseline (1991-1994), 7,800 middle-aged British men and women
      without diabetes indicated their life satisfaction, emotional vitality, and
      optimism. Diabetes status was determined by self-reported physician diagnosis and
      oral glucose tolerance test (screen detection) at baseline and through 2002-2004.
      Incident diabetes was defined by physician-diagnosed and screen-detected cases
      combined and separately. Logistic regression estimated the odds of developing
      diabetes controlling for relevant covariates (e.g., demographics, depressive
      symptoms). Models were also stratified by gender and weight status. RESULTS:
      There were 562 combined cases of incident diabetes during follow-up (up to 13
      years). Well-being was not associated with incident diabetes for combined
      physician-diagnosed and screen-detected cases. However, when examining the 288
      physician-diagnosed cases, life satisfaction and emotional vitality were
      associated with up to a 15% decrease in the odds of physician-diagnosed diabetes,
      controlling for demographics (results were similar with other covariates).
      Optimism was not associated with physician-diagnosed diabetes, and no well-being
      indicator was associated with screen-detected diabetes. Gender and weight status
      were not moderators. CONCLUSIONS: Life satisfaction and emotional vitality, but
      not optimism, were associated with reduced risk of physician-diagnosed diabetes.
      These findings suggest that well-being may contribute to reducing risk of a
      prevalent and burdensome condition, although intervention studies are needed to
      confirm this. It is unclear why findings differed for physician-diagnosed versus
      study-screened diabetes. (PsycINFO Database Record

PMID- 25603422
TI  - Impacts of soil and water pollution on food safety and health risks in China.
AB  - Environmental pollution and food safety are two of the most important issues of
      our time. Soil and water pollution, in particular, have historically impacted on
      food safety which represents an important threat to human health. Nowhere has
      that situation been more complex and challenging than in China, where a
      combination of pollution and an increasing food safety risk have affected a large
      part of the population. Water scarcity, pesticide over-application, and chemical
      pollutants are considered to be the most important factors impacting on food
      safety in China. Inadequate quantity and quality of surface water resources in
      China have led to the long-term use of waste-water irrigation to fulfill the
      water requirements for agricultural production. In some regions this has caused
      serious agricultural land and food pollution, especially for heavy metals. It is
      important, therefore, that issues threatening food safety such as combined
      pesticide residues and heavy metal pollution are addressed to reduce risks to
      human health. The increasing negative effects on food safety from water and soil
      pollution have put more people at risk of carcinogenic diseases, potentially
      contributing to 'cancer villages' which appear to correlate strongly with the
      main food producing areas. Currently in China, food safety policies are not
      integrated with soil and water pollution management policies. Here, a
      comprehensive map of both soil and water pollution threats to food safety in
      China is presented and integrated policies addressing soil and water pollution
      for achieving food safety are suggested to provide a holistic approach. 

PMID- 25603423
TI  - Anti-tumor activities of lipids and lipid analogues and their development as
      potential anticancer drugs.
AB  - Lipids have the potential for development as anticancer agents. Endogenous
      membrane lipids, such as ceramides and certain saturated fatty acids, have been
      found to modulate the viability of tumor cells. In addition, many tumors over
      express cyclooxygenase, lipoxygenase or cytochrome P450 enzymes that mediate the
      biotransformation of omega-6 polyunsaturated fatty acids (PUFAs) to potent
      eicosanoid regulators of tumor cell proliferation and cell death. In contrast,
      several analogous products from the biotransformation of omega-3 PUFAs impair
      particular tumorigenic pathways. For example, the omega-3 17,18-epoxide of
      eicosapentaenoic acid activates anti-proliferative and proapoptotic signaling
      cascades in tumor cells and the lipoxygenase-derived resolvins are effective
      inhibitors of inflammatory pathways that may drive tumor expansion. However, the
      development of potential anti-cancer drugs based on these molecules is complex,
      with in vivo stability a major issue. Nevertheless, recent successes with the
      antitumor alkyl phospholipids, which are synthetic analogues of naturally
      occurring membrane phospholipid esters, have provided the impetus for development
      of further molecules. The alkyl phospholipids have been tested against a range of
      cancers and show considerable activity against skin cancers and certain
      leukemias. Very recently, it has been shown that combination strategies, in which
      alkyl phospholipids are used in conjunction with established anticancer agents,
      are promising new therapeutic approaches. In future, the evaluation of new lipid
      based molecules in single-agent and combination treatments may also be assessed.
      This could provide a range of important treatment options in the management of
      advanced and metastatic cancer.

PMID- 25603424
TI  - Performance of three cognitive screening tools in a sample of older New
      Zealanders.
AB  - BACKGROUND: With the ubiquitous Mini-Mental State Exam now under copyright,
      attention is turning to alternative cognitive screening tests. The aim of the
      present study was to investigate three common cognitive screening tools: the
      Montreal Cognitive Assessment (MoCA), the Rowland Universal Dementia Assessment
      Scale (RUDAS), and the recently revised Addenbrooke's Cognitive Assessment
      Version III (ACE-III). METHODS: The ACE-III, MoCA and RUDAS were administered in
      random order to a sample of 37 participants with diagnosed mild dementia and 47
      comparison participants without dementia. The diagnostic accuracy of the three
      tests was assessed. RESULTS: All the tests showed good overall accuracy as
      assessed by area under the ROC Curve, 0.89 (95% CI = 0.80-0.95) for the ACE-III,
      0.84 (0.75-0.91) for the MoCA, and 0.86 (0.77-0.93) for RUDAS. The three tests
      were strongly correlated: r(84) = 0.85 (0.78-0.90) between the ACE-III and MoCA,
      0.70 (0.57-0.80) between the ACE-III and RUDAS; and 0.65 (0.50-0.76) between the
      MoCA and RUDAS. The data derived optimal cut-off points for were lower than the
      published recommendations for the ACE-III (optimal cut-point <=76, sensitivity =
      81.1%, specificity = 85.1%) and the MoCA (<=20, sensitivity = 78.4%, specificity
      = 83.0%), but similar for the RUDAS (<=22, sensitivity = 78.4%, specificity =
      85.1%). CONCLUSIONS: All three tools discriminated well overall between cases of
      mild dementia and controls. To inform interpretation of these tests in clinical
      settings, it would be useful for future research to address more inclusive and
      potentially age-stratified local norms.

PMID- 25603425
TI  - Small molecule inhibitors of disulfide bond formation by the bacterial DsbA-DsbB
      dual enzyme system.
AB  - The DsbA:DsbB redox machinery catalyzes disulfide bond formation in secreted
      proteins and is required for bacterial virulence factor assembly. Both enzymes
      have been identified as targets for antivirulence drugs. Here, we report
      synthetic analogues of ubiquinone (dimedone derivatives) that inhibit disulfide
      bond formation (IC50~1 MUM) catalyzed by E. coli DsbA:DsbB. The mechanism
      involves covalent modification of a single free cysteine leaving other cysteines
      unmodified. A vinylogous anhydride in each inhibitor is cleaved by the thiol,
      which becomes covalently modified to a thioester by a propionyl substituent.
      Cysteines and lysines on DsbA and DsbB and a nonredox enzyme were modified in a
      manner that implies some specificity. Moreover, human thioredoxin was not
      inhibited under the same conditions that inhibited EcDsbA. This proof of concept
      work uses small molecules that target specific cysteines to validate the DsbA and
      DsbB dual enzyme system as a viable and potentially druggable antivirulence
      target.

PMID- 25603426
TI  - Targeting FOXM1 auto-regulation in cancer.

PMID- 25603428
TI  - Regulation of virulence gene expression.

PMID- 25603427
TI  - Transcriptional regulation of bacterial virulence gene expression by molecular
      oxygen and nitric oxide.
AB  - Molecular oxygen (O2) and nitric oxide (NO) are diatomic gases that play major
      roles in infection. The host innate immune system generates reactive oxygen
      species and NO as bacteriocidal agents and both require O2 for their production.
      Furthermore, the ability to adapt to changes in O2 availability is crucial for
      many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic
      bacteria have evolved transcriptional regulatory systems that perceive these
      gases and respond by reprogramming gene expression. Direct sensors possess iron
      containing co-factors (iron-sulfur clusters, mononuclear iron, heme) or reactive
      cysteine thiols that react with O2 and/or NO. Indirect sensors perceive the
      physiological effects of O2 starvation. Thus, O2 and NO act as environmental cues
      that trigger the coordinated expression of virulence genes and metabolic
      adaptations necessary for survival within a host. Here, the mechanisms of signal
      perception by key O2- and NO-responsive bacterial transcription factors and the
      effects on virulence gene expression are reviewed, followed by consideration of
      these aspects of gene regulation in two major pathogens, Staphylococcus aureus
      and Mycobacterium tuberculosis. 

PMID- 25603431
TI  - Day-to-day variability in cardiorespiratory responses to hypoxic cycle exercise.
AB  - Repeatedly performing exercise in hypoxia could elicit an independent training
      response and become an unintended co-intervention. The primary purposes of this
      study were to determine if hypoxic exercise responses changed across repeated
      testing and to assess the day-to-day variability of commonly used measures of
      cardiorespiratory and metabolic responses to hypoxic exercise. Healthy young
      males (aged 23 +/- 2 years) with a maximal O2 consumption of 50.7 +/- 4.7 mL.kg(
      1).min(-1) performed 5 trials (H1 to H5) over a 2-week period in hypoxia
      (fraction of inspired oxygen = 0.13). Participants completed 3-min stages at 20%,
      40%, 60%, and 10% of individual peak power. With increasing cycle exercise
      intensity there were increases in minute ventilation, O2 consumption, CO2
      production, respiratory exchange ratio, heart rate (HR), blood lactate
      concentration, and ratings of perceived exertion for legs and respiratory system
      along with a reduction in oxyhaemoglobin saturation (%SpO2) (all p < 0.001).
      There were no systematic changes from H1 to H5 (p > 0.05). Most measures were
      highly repeatable across testing sessions with the coefficient of variation (CV)
      averaging <=10% of the mean value in all variables except O2 consumption (17%),
      CO2 production (11%) and blood lactate concentration (17%). For HR and %SpO2 the
      CV was <5%. The exercise protocol did not elicit a training response when
      repeated 5 times during a 2-week period and the variability of exercise responses
      was low. We conclude that this protocol allows detection of small changes in
      cardiorespiratory responses to hypoxic exercise that might occur during exposure
      to hypoxia. 

PMID- 25603432
TI  - Acute changes in substrate oxidation do not affect short-term food intake in
      healthy boys and men.
AB  - The acute relationship between substrate oxidation as measured by respiratory
      exchange ratio (RER) and food intake (FI) has not been defined. The purpose of
      the study was to determine acute relationships between RER, modified by exercise
      and a glucose load, and FI and net energy balance (NEB) in physically active
      normal-weight boys and men. In a crossover design, 15 boys (aged 9-12 years) and
      15 men (aged 20-30 years) were randomly assigned to 4 conditions: (i) water and
      rest, (ii) glucose-drink and rest, (iii) water and exercise, and (iv) glucose
      drink and exercise. Indirect calorimetry was used to determine RER, energy
      expenditure, and carbohydrate and fat oxidation. Subjective appetite and blood
      glucose were also measured. RER was higher after glucose (0.91 +/- 0.01) compared
      with water (0.87 +/- 0.01) (p < 0.0001), and after exercise (0.91 +/- 0.01)
      compared with rest (0.88 +/- 0.01) (p = 0.0043) in men (0.91 +/- 0.01) compared
      with boys (0.88 +/- 0.01) (p = 0.0002). FI (kcal.m(-2)) did not differ between
      boys and men. Glucose (582 +/- 24 kcal.m(-2)) reduced FI compared with water (689
      +/- 25 kcal.m(-2)) (p < 0.0001), and further decreased FI when combined with
      exercise (554 +/- 34 kcal.m(-2)) (p = 0.0303). NEB was reduced with exercise (573
      +/- 25 kcal.m(-2)) compared with the sedentary condition (686 +/- 24 kcal.m(-2))
      (p < 0.0001), but was higher after the glucose drink (654 +/- 27 kcal.m(-2))
      compared with water (605 +/- 25 kcal.m(-2)) (p = 0.0267). No correlations were
      found between RER and FI or NEB in boys and men, except in the control condition
      of resting with water. In conclusion, the short-term modification of substrate
      oxidation by glucose and/or exercise in normal weight and active boys and men did
      not affect FI and NEB. 

PMID- 25603433
TI  - Objective estimation for uncertainty of restoring corneal topography surface.
AB  - PURPOSE: Mapping corneal topography (CT) measurement data into a desired area can
      be based on data interpolation or fitting available data onto orthogonal
      functions. The restored CT map covers the entire area of interest, although its
      accuracy remains unknown. Here, a mathematical algorithm is presented for CT data
      assimilation, which yields both an entire CT map and an objective estimation of
      the map restoration accuracy. METHODS: All available CT elevation data are fitted
      on Zernike polynomials. Then, a Kalman filter is used to combine CT measurement
      data together with a priori statistics of Zernike coefficients estimated for the
      general population. The proposed technique yields the statistically optimal
      estimation for CT Zernike amplitudes and their covariance matrix. The entire CT
      elevation map is restored from Zernike amplitudes, and the amplitude covariance
      matrix is converted into a CT uncertainty map, which provides an objective
      estimate of the CT map quality. RESULTS: The performance of the proposed method
      is demonstrated using CT data from a retrospective clinical study. The restored
      CT map has the highest uncertainty in measurement gaps, where no CT data are
      available. This uncertainty is close to the a priori variance of the general
      population. CONCLUSIONS: Corneal topography mapping, based on the Kalman filter,
      constitutes a statistically optimal method of measurement data assimilation. It
      combines measurement data weighted by their quality and a priori knowledge of
      corneal shape, which protects the results from measurement outliers. The
      uncertainty magnitude depends on the number of pixels and the measurement noise
      level.

PMID- 25603429
TI  - Regulation of bacterial virulence gene expression by cell envelope stress
      responses.
AB  - The bacterial cytoplasm lies within a multilayered envelope that must be
      protected from internal and external hazards. This protection is provided by cell
      envelope stress responses (ESRs), which detect threats and reprogram gene
      expression to ensure survival. Pathogens frequently need these ESRs to survive
      inside the host, where their envelopes face dangerous environmental changes and
      attack from antimicrobial molecules. In addition, some virulence genes have
      become integrated into ESR regulons. This might be because these genes can
      protect the cell envelope from damage by host molecules, or it might help ESRs to
      reduce stress by moderating the assembly of virulence factors within the
      envelope. Alternatively, it could simply be a mechanism to coordinate the
      induction of virulence gene expression with entry into the host. Here, we briefly
      describe some of the bacterial ESRs, followed by examples where they control
      virulence gene expression in both Gram-negative and Gram-positive pathogens. 

PMID- 25603434
TI  - Stemness characteristics of human corneal endothelial cells cultured in various
      media.
AB  - PURPOSE: To investigate stemness characteristics of human corneal endothelial
      cells (HCECs) cultured in various media. METHODS: Human corneal endothelial cells
      were isolated using a sphere-forming assay. Cells were allowed to attach to the
      bottom of culture plates and were cultured in different media designated as
      medium A (Opti-MEM I with 8% fetal bovine serum), medium B (DMEM/F12 with B27
      supplement), medium E (DMEM/F12 with epidermal growth factor [EGF]), and medium
      BE (DMEM/F12 with B27 supplement and EGF), respectively. Cell morphology was
      evaluated with an phase-contrast inverted microscope. Immunofluorescence staining
      and western blotting of nestin, octamer-binding transcription factor (OCT3/4),
      glial fibrillary acidic protein (GFAP), zonula occludens-1 (ZO-1), collagen VIII
      alpha2, and Na-K ATPase was performed. Cell proliferation was assessed with a
      cell counting kit-8 assay. RESULTS: A few cultured cells stained with nestin. The
      cells cultured in medium A expressed high levels of GFAP, OCT3/4, and nestin, and
      higher levels of ZO-1 were expressed in the cells cultured in medium A and medium
      B compared with cells cultured in the other media. The cells cultured in medium A
      assumed a fibroblast-like shape, whereas the cells cultured in medium B and
      medium BE appeared as mosaics. Cell proliferation was highest in medium A
      compared with those cultured in the other media. CONCLUSIONS: Cultured HCECs
      expressed stem cell markers, including nestin, OCT3/4, and GFAP. The expression
      of stem cell markers differed according to the culture media and associated
      proliferation rate.

PMID- 25603430
TI  - Regulation of transcription by eukaryotic-like serine-threonine kinases and
      phosphatases in Gram-positive bacterial pathogens.
AB  - Bacterial eukaryotic-like serine threonine kinases (eSTKs) and serine threonine
      phosphatases (eSTPs) have emerged as important signaling elements that are
      indispensable for pathogenesis. Differing considerably from their histidine
      kinase counterparts, few eSTK genes are encoded within the average bacterial
      genome, and their targets are pleiotropic in nature instead of exclusive. The
      growing list of important eSTK/P substrates includes proteins involved in
      translation, cell division, peptidoglycan synthesis, antibiotic tolerance,
      resistance to innate immunity and control of virulence factors. Recently it has
      come to light that eSTK/Ps also directly modulate transcriptional machinery in
      many microbial pathogens. This novel form of regulation is now emerging as an
      additional means by which bacteria can alter their transcriptomes in response to
      host-specific environmental stimuli. Here we focus on the ability of eSTKs and
      eSTPs in Gram-positive bacterial pathogens to directly modulate transcription,
      the known mechanistic outcomes of these modifications, and their roles as an
      added layer of complexity in controlling targeted RNA synthesis to enhance
      virulence potential. 

PMID- 25603435
TI  - Femtosecond-assisted intrastromal corneal single-segment ring implantation in
      patients with keratoconus: a 12-month follow-up.
AB  - OBJECTIVE: To determine visual rehabilitation in patients with keratoconus who
      received femtosecond-assisted intrastromal corneal single-segment ring
      implantation. METHODS: This prospective study was conducted on 62 eyes of 45
      patients with keratoconus who received single-segment Intacs. The FS200
      femtosecond laser was used for tunnel creation. Patients were examined for
      astigmatism, uncorrected visual acuity (UCVA), best-corrected visual acuity
      (BCVA), and manifest refraction spherical equivalent (MRSE) before the operation
      and 1, 6, and 12 months after operation. Scheimpflug imaging including minimum
      keratometry reading (min-K), maximum keratometry reading (max-K), average of
      minimum and maximum keratometry readings (mean-K), central corneal thickness
      (CCT), asphericity (Q-value), index of surface variance (ISV), index of vertical
      asymmetry (IVA), keratoconus index (KI), center keratoconus index (CKI), index of
      height asymmetry (IHA), index of height decentration (IHD), and minimum sagittal
      curvature (Rmin) was performed before and 12 months after the operation. RESULTS:
      The mean preoperative UCVA was 20/130, which increased to 20/62 1 year after the
      operation (P < 0.001). The mean BCVA in the last follow-up was 20/32, which
      improved when compared with preoperative BCVA (20/40) (P = 0.008). One year after
      the operation, MRSE and cylinder decreased to 1.33 +/- 1.90 diopter (D) and 0.46
      +/- 1.50 D, respectively (P < 0.001 for both). Min-K, max-k, and mean-k reduced
      to 1.67 +/- 0.1.40 D, 2.08 +/- 1.84 D, and 1.85 +/- 1.30 D (P < 0.001 for all). Q
      value decreased to 0.81 +/- 1.14 (P < 0.001). In contrast, CKI had a significant
      increase of 0.02 (P = 0.002). Other evaluated indexes did not show any
      significant differences. CONCLUSION: Implantation of the single-segment ring in
      patients with keratoconus improved vision because of regularizing the cornea and
      centralization of the corneal cone.

PMID- 25603436
TI  - Impact of Donor Age on Corneal Endothelium-Descemet Membrane Layer Scroll
      Formation.
AB  - OBJECTIVE: To correlate corneal endothelium-Descemet membrane (EDM) layer
      parameters of scroll tightness with donor age, endothelial cell density (ECD),
      and history of diabetes. METHODS: Endothelium-Descemet membrane layer scrolls
      were harvested from 26 corneoscleral buttons using the SCUBA technique by a
      cornea-fellowship trained ophthalmologist masked to donor age. Two independent
      outcome parameters were used to characterize the scrolling severity of
      successfully harvested tissue: scroll width and tendency for EDM scroll formation
      (referred to as scroll rating on a 1-4 scale: incomplete scroll formation to
      tightly scrolled). RESULTS: Mean donor age was 59 +/- 17 (15-69) years. Mean ECD
      of EDM scroll was 2,451 +/- 626 (range: 1,307-3,195) cells per square millimeter.
      Using stepwise linear regression, a significant correlation was found between
      scroll width and donor age (R=0.497, P<0.05). Additionally, a significant inverse
      correlation was found between scroll width and ECD (R=-0.605, P<0.05). There was
      no statistically significant correlation between a donor history of diabetes and
      the parameters of scrolling tendency. CONCLUSIONS: Our data suggest that using
      older donors reduces EDM scroll tightness.

PMID- 25603437
TI  - Post-photorefractive keratectomy contact lens microbiological findings of
      individuals who work in a hospital environment.
AB  - OBJECTIVE: To describe the microbiological findings from bandage contact lenses
      in patients who work in a hospital environment submitted to photorefractive
      keratectomy (PRK). METHODS: This prospective comparative case series enrolled 43
      eyes of 22 volunteers (28.05 +/- 3.50 years). Fourteen individuals (n = 27) were
      health care professionals who work in health care facilities or community
      physician's offices. Eight individuals (n = 16) were patients who do not work in
      hospital environment. Photorefractive keratectomy was performed using standard
      technique, and a silicone hydrogel bandage contact lens was placed on the cornea
      and evaluated for adequate fit. Seven days after surgery, the bandage lenses were
      removed and imprinted in the following culture media: blood agar, chocolate agar,
      anaerobic-selective agar, and Sabouraud agar. When microbial growth was detected,
      the microorganism was identified, colony-forming units were quantified, and
      morphology and Gram-staining properties were analyzed. All isolates were tested
      for susceptibility to various antibiotics. Significance was assessed by Fisher
      exact test. RESULTS: Microbial growth was detected in 16.27% of all contact
      lenses samples. No fungi or anaerobes were found. Microbial growth was only
      observed in bandage lenses removed from patients who work in hospital
      environments. Most microorganisms found were sensitive to all antibiotics tested.
      CONCLUSION: These results suggest that working in hospital environments increase
      contamination of the contact lenses after PRK.

PMID- 25603438
TI  - Effect of nepafenac eye drops on pain associated with pterygium surgery.
AB  - OBJECTIVE: To assess the effects of nepafenac ophthalmic suspension 0.1% for
      control of pain in patients undergoing pterygium surgery. METHODS: This
      randomized, double-masked placebo-controlled study included 62 adults undergoing
      pterygium surgery. Patients were randomly assigned to receive nepafenac
      ophthalmic suspension 0.1% or balanced salt solution placebo. They were asked to
      assess the level of pain using an 11-point numeric rating scale at 6, 12, 24, 48,
      and 72 hr after surgery. Patients also were evaluated daily for the progression
      of corneal epithelial healing until complete closure was observed. RESULTS:
      Except at 72 hr after surgery, the patients reported significantly less pain in
      eyes receiving nepafenac than in eyes receiving placebo. There was no statistical
      difference between the two groups in corneal epithelial healing. CONCLUSIONS:
      Treatment with nepafenac ophthalmic suspension 0.1% significantly reduced
      postoperative pain compared with placebo after pterygium surgery.

PMID- 25603439
TI  - Autologous serum eye drops for the treatment of ocular surface disease.
AB  - OBJECTIVE: To examine the evidence for the role of autologous serum eye drops
      (ASD) in disease of the ocular surface. METHODS: A search of the literature
      published through May 2014 using PubMed, the ISI Web of Knowledge database, and
      the Cochrane Library was performed. Qualified articles were selected after review
      of titles, abstracts, and references. RESULTS: There was a significant
      improvement in either symptoms or some of the clinical examination findings,
      including tear breakup time, corneal staining, Schirmer values, and impression
      cytology in eyes with persistent corneal epithelial defect, graft-versus-host
      disease, Sjogren- and non-Sjogren-related dry eye disease, limbal stem-cell
      deficiency, recurrent corneal erosion, superior limbic keratoconjunctivitis, and
      postrefractive surgery. However, most of the studies were nonrandomized in
      nature. CONCLUSIONS: Despite the paucity of strong supporting evidence from
      randomized double-masked clinical studies, there seems to be a trend toward
      superiority of ASD in alleviating some of the clinical signs and symptoms
      associated with corneal pathology in a variety of conditions that affect the
      ocular surface compared with conventional lubricating drops/ointments.

PMID- 25603440
TI  - Repeatability and Diurnal Variation of Tear Ferning Test.
AB  - OBJECTIVES: To investigate tear ferning (TF) test repeatability between sessions
      by observing changes in the tear fern pattern during the day. METHODS: Twenty
      three healthy young adults (15 men and 8 women), ranging in age from 20 to 32
      years (mean +/- SD: 22.9 +/- 3.3 years) without signs or symptoms of dry eye
      disease, ocular disease, or contact lens wear were enrolled in the study.
      Schirmer I, tear break-up time (TBUT) test, and McMonnies questionnaire were used
      to screen volunteers. Schirmer I and TBUT tests were applied to both eyes in each
      subject. Four samples of tear fluid were collected from the right eye of each
      subject using glass capillaries at set intervals during a single day (9 AM, 11
      AM, 2 PM, and 4 PM). The TF patterns obtained from samples were classified
      according to the Masmali TF grading scale to increments of 0.1. RESULTS: The
      median values obtained from the McMonnies, Schirmer, and TBUT tests were 4.0 +/-
      2.0, 30.0 +/- 7.0 mm (OD), and 16.0 +/- 10.0 sec (OD), respectively. There were
      no statistically significant differences between the TF grades for tear samples
      collected at different times of the day (Wilks' Lambda, P = 0.351). The majority
      (84.8%) of TF grades was between 0.0 and 1.5; the remaining 15.2% of subjects had
      TF between grades 1.6 and 1.9. The overall mean grade for the TF was 1.1 +/- 0.3.
      There were small insignificant correlations between TF grades and the McMonnies
      questionnaire (r = 0.1.30) and TBUT (r = 0.248) and a negligible correlation with
      Schirmer test (r = -0.046). CONCLUSIONS: The results found no significant
      differences within the TF for tear samples collected at different times of the
      day, suggesting that there is little diurnal variation evident.

PMID- 25603441
TI  - Contact Lens-Related Acanthamoeba Keratitis and Accompanying Dacryoadenitis.
AB  - OBJECTIVES: In this study, by presenting four cases, we aimed to discuss the
      clinical presentation, diagnosis, therapy, and methods for prevention of
      Acanthamoeba keratitis (AK) and to emphasize that inflammatory dacryoadenitis can
      be seen together with it. METHODS: This is a retrospective case series of four
      eyes of four wearers of hydrophilic soft contact lenses who developed AK. The
      diagnosis was based on clinical signs, disease course, and confocal microscopy
      results. In cases with dacryoadenitis, in addition to clinical findings, magnetic
      resonance imaging was used to establish the diagnosis. RESULTS: All of the cases
      were using their contact lenses without supervision of an ophthalmologist under
      inappropriate conditions such as swimming in a pool and during steam bath. The
      diagnosis was established, and the treatment was performed within the standard
      protocol for AK. Two of the patients had low visual acuity at the level of
      counting fingers with corneal scar, cataract, and glaucoma, whereas the other two
      healed with fewer complications and achieved better vision. Two of the 4 cases
      (50%) presented with dacryoadenitis accompanying the AK. Lacrimal gland swelling
      improved in conjunction with symptoms of keratitis without specific treatment for
      dacryoadenitis in these two cases. CONCLUSIONS: Despite the improvements in
      diagnostic tests and treatment strategies for AK, the role of prevention becomes
      apparent because of the bad prognosis of this serious complication; thus, contact
      lens wearers should be aware of the importance of using lenses under
      ophthalmologist's supervision. In addition, we would like to emphasize that AK
      may be frequently associated with lacrimal gland inflammation.

PMID- 25603442
TI  - Corneal Polishing After Pterygium Excision With Motorized Diamond Burr: A
      Randomized Control Trial.
AB  - PURPOSE: To evaluate outcomes of motorized diamond burr polishing versus manual
      polishing after pterygium excision. SETTING: Dr. Rajendra Prasad Center for
      Ophthalmic Sciences, New Delhi. DESIGN: A randomized, interventional observer
      masked controlled trial. METHODS: Forty consecutive eyes underwent pterygium
      excision with fibrin, glue-assisted conjunctival autograft. In group 1 (20 eyes),
      polishing of the corneal bed was done using a crescent blade, and in group 2 (20
      eyes), using a motorized diamond burr. RESULTS: There was no difference in the 2
      groups with respect to mean age (P=0.08), gender (P=0.3), preoperative
      uncorrected visual acuity (UCVA) (P=0.45), best spectacle-corrected visual acuity
      (BCVA) (P=0.52), spherical equivalent (P=0.5), mean astigmatism (P=0.7), tear
      function tests like tear break-up time, tear film meniscus height, Schirmer I and
      II (P=0.6, 0.5, 0.7, 0.9 respectively), pterygium dimension (P=0.4), and
      conjunctival autograft size (P=0.24). Mean intraoperative surgical time was
      significantly more in group 1 (16.9 +/- 2.85 min) as compared with 12.25 +/- 1.88
      min in group 2 (P=0.0001). Postoperatively, there was a statistically significant
      reduction in astigmatism and improvement in UCVA, BCVA, spherical equivalent in
      all eyes. No difference was found in mean epithelial defect healing time, UCVA,
      BCVA, astigmatism, tear film break-up time, Schirmer I and II, and tear meniscus
      height at 6 months between 2 groups; however, significantly better UCVA was found
      in group 2 at 3 months (P=0.04). Surgically induced astigmatism (SIA) was
      significantly more in group 2 as compared with group 1 at 6 months (P=0.0006).
      CONCLUSIONS: Motorized diamond burr polishing of the corneoscleral bed during
      primary pterygium excision in comparison with manual polishing requires
      significantly lesser surgical time with better UCVA, decreased astigmatism, and
      greater SIA at 6 months, which indicates greater astigmatic correction.

PMID- 25603443
TI  - Impact of Hydration Media on Ex Vivo Corneal Elasticity Measurements.
AB  - OBJECTIVES: To determine the effect of hydration media on ex vivo corneal
      elasticity. METHODS: Experiments were conducted on 40 porcine eyes retrieved from
      an abattoir (10 eyes each for phosphate-buffered saline (PBS), balanced salt
      solution, Optisol, 15% dextran). The epithelium was removed, and the cornea was
      excised with an intact scleral rim and placed in 20% dextran overnight to restore
      its physiological thickness. For each hydration media, corneas were evenly
      divided into two groups: one with an intact scleral rim and the other without.
      Corneas were mounted onto a custom chamber and immersed in a hydration medium for
      elasticity testing. Although in each medium, corneal elasticity measurements were
      performed for 2 hr: at 5-min intervals for the first 30 min and then 15-min
      intervals for the remaining 90 min. Elasticity testing was performed using
      nanoindentation with spherical indenters, and Young modulus was calculated using
      the Hertz model. Thickness measurements were taken before and after elasticity
      testing. RESULTS: The percentage change in corneal thickness and elasticity was
      calculated for each hydration media group. Balanced salt solution, PBS, and
      Optisol showed an increase in thickness and Young moduli for corneas with and
      without an intact scleral rim. Fifteen percent dextran exhibited a dehydrating
      effect on corneal thickness and provided stable maintenance of corneal elasticity
      for both groups. CONCLUSIONS: Hydration media affects the stability of corneal
      thickness and elasticity measurements over time. Fifteen percent dextran was most
      effective in maintaining corneal hydration and elasticity, followed by Optisol.

PMID- 25603444
TI  - Miraflow, Soft Contact Lens Cleaner: Activity Against Acanthamoeba Spp.
AB  - OBJECTIVE: Miraflow is a cleaner for soft contact lens which contains 20%
      isopropyl alcohol. The purpose of this study was to determine the activity
      against Acanthamoeba trophozoites and cysts for Miraflow. In addition, to
      determine the activity of combined Miraflow and multipurpose solutions (MPSs)
      against Acanthamoeba cysts. METHODS: Two simulated-use studies were conducted.
      The significance in the log reduction in the number of trophozoites and cysts of
      A. castellanii strains ATCC 50514 and ATCC 50370 or A. polyphaga ATCC 30461 after
      exposure to Miraflow alone was determined by the Spearman-Karber method. To
      examine the activity against Acanthamoeba of combined Miraflow and an MPS, the
      log reduction in the number of cysts after a 1-min exposure to Miraflow followed
      by a 4-hr exposure to MPS (ReNu fresh) was also determined. RESULTS: Short-time
      exposure of 30 sec to Miraflow demonstrated activity against the Acanthamoeba
      trophozoites. However, a 1-min treatment was only relatively effective (1.1 log
      reduction) against the cysts of A. castellanii ATCC 50514, but no statistically
      significant reduction was observed for the cysts of the other 2 strains. The
      combined use with Miraflow and MPS demonstrated activity against the cysts, and a
      3.0, 1.0, or 1.5 log reduction in the numbers was obtained for A. castellanii
      ATCC 50514, A. castellanii ATCC 50370, and A. polyphaga ATCC 30461, respectively.
      CONCLUSIONS: Exposure to combined Miraflow and MPS resulted in reductions in the
      number of Acanthamoeba cysts.

PMID- 25603445
TI  - Effective Gene Delivery to Valvular Interstitial Cells Using Adeno-Associated
      Virus Serotypes 2 and 3.
AB  - Currently, curative therapies for heart valve diseases do not exist, thus
      motivating the need for new therapeutics, regenerative and tissue-engineered
      valves, and further basic research into pathological mechanisms. For studying
      valve diseases and developing valve therapies, effective methods to manipulate
      gene expression in primary valvular interstitial cells (VICs), which promote
      calcification in disease, would be valuable. Unfortunately, there is little
      information reported about effective gene delivery methods for VICs. Adeno
      associated virus (AAV) is a clinically proven gene delivery vector capable of
      transducing many cell types and tissues, but has not yet been reported to infect
      valvular cells. In this study, AAV serotypes 1-9 were tested for their ability to
      deliver a green fluorescent protein (GFP) reporter into VICs in vitro. Flow
      cytometry results indicate AAV2 and AAV3 are capable of transducing VICs more
      efficiently than other serotypes. Furthermore, transduction efficiencies can be
      optimized by increasing the multiplicity of infection (MOI) and using self
      complementary, double-stranded genomes, yielding up to 98% successfully
      transduced cells. Transduction of VICs by AAV2 or AAV3 in the presence of
      competing soluble heparin significantly reduces delivery efficiencies, suggesting
      heparan sulfate proteoglycans act as the primary VIC receptors of these two
      serotypes. Overall, this study establishes AAV2 and AAV3 as efficient gene
      delivery vehicles for primary VICs. Such effective delivery vectors for valve
      cells may be broadly useful for numerous applications, including the study of
      valvular cell biology, development of valve disease therapies, and regulation of
      genes for tissue engineering heart valves. 

PMID- 25603446
TI  - Suitability of Different Food Grade Materials for the Encapsulation of Some
      Functional Foods Well Reported for Their Advantages and Susceptibility.
AB  - Functional foods find a very important place in the modern era, where different
      types of cancer, diabetes, cardiovascular diseases, etc. are on a high.
      Irrespective of the abundance of bioactive components in different fruits and
      vegetables, their low solubility in aqueous solution, vulnerability to
      destruction in different environmental and gastrointestinal conditions and a low
      intestinal absorption becomes a concern. Because it is quite difficult to
      commercialize non food materials for the food encapsulation purposes due to their
      safety concerns in the human body, scientists in the recent times have come up
      with the idea of encapsulating the different bioactive components in different
      food grade materials that are able to safeguard these bioactive components
      against the different environmental and gastrointestinal conditions and ensure
      their safe and targeted delivery at their absorption sites. Different food grade
      encapsulation materials including various oligosaccharides, polysaccharides
      (starch, cyclodextrins, alginates, chitosan, gum arabic, and carboxymethyl
      cellulose) and proteins and their suitability for encapsulating various bioactive
      components like flavonoids (catechins, rutin, curcumin, hesperetin, and
      vanillin), nonflavonoids (resveratrol), carotenoids (beta-carotene, lycopene, and
      lutein), and fatty acids (fish oil, flaxseed oil, and olive oil) of high medical
      and nutritional value are reviewed here.

PMID- 25603447
TI  - What's in a label?

PMID- 25603448
TI  - Clinical utility of the DSM-5 alternative model of personality disorders: six
      cases from practice.
AB  - In Section III, Emerging Measures and Models, DSM-5 presents an Alternative Model
      of Personality Disorders, which is an empirically based model of personality
      pathology measured with the Level of Personality Functioning Scale (LPFS) and the
      Personality Inventory for DSM-5 (PID-5). These novel instruments assess level of
      personality impairment and pathological traits. Objective. A number of studies
      have supported the psychometric qualities of the LPFS and the PID-5, but the
      utility of these instruments in clinical assessment and treatment has not been
      extensively evaluated. The goal of this study was to evaluate the clinical
      utility of this alternative model of personality disorders. Method. We
      administered the LPFS and the PID-5 to psychiatric outpatients diagnosed with
      personality disorders and other nonpsychotic disorders. The personality profiles
      of six characteristic patients were inspected (involving a comparison of
      presenting problems, history, and diagnoses) and used to formulate treatment
      considerations. We also considered 6 specific personality disorder types that
      could be derived from the profiles as defined in the DSM-5 Section III criteria.
      Results. Using the LPFS and PID-5, we were able to characterize the 6 cases in a
      meaningful and useful manner with regard to understanding and treatment of the
      individual patient and to match the cases with 6 relevant personality disorder
      types. Implications for ease of use, communication, and psychotherapy are
      discussed. Conclusion. Our evaluation generally supported the utility for
      clinical purposes of the Alternative Model for Personality Disorders in Section
      III of the DSM-5, although it also identified some areas for refinement. (Journal
      of Psychiatric Practice 2015;21:3-25). 

PMID- 25603449
TI  - Use of antipsychotic medications in pediatric and young adult populations: future
      research needs.
AB  - The use of antipsychotics, particularly second generation antipsychotics, among
      children and adolescents has increased markedly during the past 20 years.
      Existing evidence gaps make this practice controversial and hinder treatment
      decision-making. This article describes and prioritizes future research needs
      regarding antipsychotic treatment in youth, focusing on within-class and between
      class drug comparisons with regard to key population subgroups, efficacy and
      effectiveness outcomes, and adverse event outcomes. Using as a foundation a
      recent systematic review of antipsychotic treatment among youth, which was
      completed by a different Evidence-based Practice Center, we worked with a diverse
      group of 12 stakeholders representing researchers, funders, health care
      providers, patients, and families to identify and prioritize research needs. From
      an initial list of 16 evidence gaps, we enumerated 6 high-priority research
      needs: 1) long-term comparative effectiveness across all psychiatric disorders;
      2) comparative long-term risks of adverse outcomes; 3) short-term risks of
      adverse events; 4) differentials of efficacy, effectiveness, and safety for
      population subgroups; 5) comparative effectiveness among those with attention
      deficit/hyperactivity disorder and disruptive behavior disorders and common
      comorbidities; 6) comparative effectiveness among those with bipolar disorder and
      common comorbidities. In this article, we describe these future research needs in
      detail and discuss study designs that could be used to address them.

PMID- 25603450
TI  - Biomarker identification in psychiatric disorders: from neuroscience to clinical
      practice.
AB  - Patients with psychiatric disorders exhibit several neurobehavioral and
      neuropsychological alterations compared to healthy controls. However, signature
      endpoints of these behavioral manifestations have not yet been translated into
      clinical tests for diagnosis and follow-up measures. Recently, neuroproteomic
      approaches have been utilized to identify unique signature markers indicative of
      these disorders. Development of reliable biomarkers has the potential to
      revolutionize the diagnosis, classification, and monitoring of clinical responses
      in psychiatric diseases. However, the lack of biological gold standards, the
      evolving nosology of psychiatric disorders, and the complexity of the nervous
      system are among the major challenges that have hindered efforts to develop
      reliable biomarkers in the field of neuropsychiatry and drug abuse. While
      biomarkers currently have a limited role in the area of neuropsychiatry, several
      promising biomarkers have been proposed in conditions such as dementia,
      schizophrenia, depression, suicide, and addiction. One of the primary objectives
      of this review is to discuss the role of proteomics in the development of
      biomarkers specific to neuropsychiatry. We discuss and evaluate currently
      available biomarkers as well as those that are under research for clinical use in
      the future.

PMID- 25603451
TI  - Inpatient treatment for anorexia nervosa: a systematic review of randomized
      controlled trials.
AB  - BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric disease. Choice of
      acute inpatient care for AN is driven by the severity of symptoms and the level
      of risk to the patient. Inpatient hospitalization of patients with AN typically
      includes a behavioral weight gain protocol that is designed to address the core
      features of the disorder: weight, appetite, and distorted thoughts and behavior.
      Some add-on treatments may also be included in the inpatient treatment model and
      may have potential benefits, including faster or greater weight gain; such
      treatments include psychotherapy, psychoeducation, pharmacological treatment, and
      nutritional replacement. OBJECTIVE: The goal of this study was to systematically
      review randomized clinical trials (RCTs) that have compared the efficacy of
      different forms of add-on treatment delivered during admission to a 24-hour
      hospital and to summarize the existing data regarding weight gain associated with
      such pharmacological, medical, and psychological interventions. METHODS:
      Systematic electronic and manual searches were conducted to identify published
      RCTs concerning inpatient treatment of AN. Weight gain was used as the main
      outcome variable. RESULTS: Overall, no significant increase in weight recovery
      was reported with atypical antipsychotics compared to placebo or therapy as
      usual. Only one study showed slight benefits in young patients during
      hospitalization (d=0.77; 95% confidence interval [CI] -0.09-1.64). No significant
      effects on weight recovery were found for antidepressants (d=-0.10; 95% CI=-0.63
      0.42). In addition, none of the add-on psychotherapy techniques that were
      evaluated demonstrated superiority compared with control interventions in the
      inpatient setting. Cyclic enteral nutrition was studied in one RCT in which it
      demonstrated superiority compared to oral refeeding only (d=0.97; 95% CI=0.51
      1.47). Other less common treatments such as bright light therapy and lithium
      carbonate were not found to produce additional significant weight improvement
      compared with placebo. CONCLUSION: Most add-on treatments during the acute
      inpatient phase of AN treatment are not effective in increasing weight recovery.
      Long-term follow-up studies after the acute treatment phase are needed to make
      evidence-based recommendations.

PMID- 25603452
TI  - CNS drug development: lessons learned part 2. Symptoms, not syndromes as targets
      consistent with the NIMH research domain approach.
AB  - This column is the second in a series exploring lessons for psychiatric drug
      development that can be learned from the development of 6 central nervous system
      drugs with novel mechanisms of action over the past 25 years. Part 1 presented a
      brief overview of the neuroscience that supported the development of each of
      these drugs, including the rationale for selecting their targets and indications.
      This column reviews specific principles involved in the development of these 6
      drugs that have important implications for the future of psychiatric drug
      development. These include focusing on efficacy for a specific symptom or
      behavior rather than a broad syndrome, choosing a target in the brain with a
      specific behavioral output that is conserved from lower mammalian to human
      brains, and measuring outcomes based on behavioral phenomena that can be readily
      measured in an unambiguous parametric way. It is hoped that the Research Domain
      Criteria initiative of the National Institute of Health will promote research
      advances consistent with this model.

PMID- 25603453
TI  - The forensic psychiatric report.
AB  - The construction of a written forensic report is a core component of forensic
      practice, demonstrating the evaluator's skill in conducting the evaluation and in
      communicating relevant information to the legal audience in an effective manner.
      Although communication skills and quality of written documentation are important
      in clinical psychiatry generally, they form the sine qua non of successful
      forensic work, which consists in telling complex stories in a coherent and
      compelling fashion. High quality forensic reports require careful preparation
      from the earliest stages of work on a case. They generally follow an expected
      structure, which permits the evaluator to provide all the data necessary to form
      a carefully reasoned opinion that addresses the legal questions posed. Formats
      and content of reports vary according to the type of case and the circumstances
      of the evaluation and so require flexibility within customary frameworks. The
      style and quality of writing are critical to the crafting of forensic reports.
      The effects on legal decision-makers of various approaches to the presentation of
      information in reports has not been studied empirically, but guidance from
      experienced forensic psychiatrists is available. There is a small body of
      research on quality improvement in forensic writing, and further empiric study is
      warranted.

PMID- 25603454
TI  - Integrating real-time feedback of outcome assessment for individual patients in
      an inpatient psychiatric setting: a case study of personalized psychiatric
      medicine.
AB  - Routine assessment of psychiatric patient outcomes is rare, despite growing
      evidence that feedback to clinicians and patients concerning patient progress
      improves treatment outcomes. The authors present a case in which real-time
      feedback proved beneficial in the treatment of a woman with a personality
      disorder admitted for inpatient treatment due to worsening depression, anxiety,
      severe suicide risk, and decline in functioning. During the course of her 10-week
      hospitalization, she completed standardized assessments of symptoms/functioning
      at admission, at 2 week intervals, and at discharge. The distinctive feature of
      this case is the way in which real-time feedback to the treatment team,
      psychiatrist, and patient exposed hidden treatment barriers. In the midst of an
      improving profile with decreasing symptom severity, the patient experienced a
      spike in distress and symptoms, prompting her treatment team to examine the
      treatment plan and to engage the patient around understanding the decline in
      functioning. This intervention revealed a replay of a familiar pattern in the
      patient's life that led to the identification and repair of a rupture in the
      therapeutic alliance and to an improvement in the patient's functioning. This
      case expands on previous research concerning the integration of individualized
      assessments into outpatient treatment and it illustrates the need to extend
      outpatient research to inpatient settings.

PMID- 25603455
TI  - Mind-language in the age of the brain: is "mental illness" a useful term?
AB  - The term "mental illness" has been criticized on a variety of grounds, most
      notably by those who have argued that the term is merely a "myth" or a
      "metaphor." Some have argued that if and when so-called mental illnesses are
      exhaustively explained by disturbed brain function or structure, we will no
      longer need the term "mental illness," on the supposition that neuropathology and
      psychopathology are mutually exclusive constructs. The author argues that, on the
      contrary, the locution "mental illness" is not rendered useless or unnecessary
      when neuropathology is discovered, nor is the term "mental illness" a metaphor.
      Rather, it is an instance of "ordinary language" that we apply quite literally to
      certain types of suffering and incapacity in the realm of thought, emotion,
      cognition, and behavior. Although its use carries the risk of perpetuating mind
      body dualism and it may be misused as a pejorative label, "mental illness" is
      likely to remain a useful and meaningful descriptive term, even as we discover
      the neurobiological underpinnings of psychiatric illness.

PMID- 25603457
TI  - Multielectrocatalysis by layer-by-layer films based on pararosaniline and
      vanadium-substituted phosphomolybdate.
AB  - Hybrid multilayer films based on the two molecular species pararosaniline (PR)
      and Keggin-type polyoxometalate K5[PMo11VO40)] (PMo11V) were prepared on
      different substrates using the electrostatic layer-by-layer (LbL) self-assembly
      method. The film buildup, monitored by electronic spectroscopy, showed a regular
      stepwise growth, and X-ray photoelectron spectroscopy data confirmed the presence
      of both molecular components within the LbL films. Scanning electron microscopy
      images revealed a completely covered surface with a nonuniform distribution of
      film components, and atomic force microscopy images confirmed a rough surface.
      The film electrochemical responses and permeability were studied by cyclic
      voltammetry. Films revealed three Mo-based redox processes (Mo(VI) -> Mo(V)) and
      one V-based redox process (V(V) -> V(IV)) in the potential range between 0.8 and 
      0.4 V vs Ag/AgCl. Studies with the redox probes [Fe(CN)6](3-/4-) and
      [Ru(NH3)6](3+/2+) showed that the films maintain the permeability even after six
      bilayers. Furthermore, the {PR/PMo11V}n multilayer films exhibit excellent Mo
      based electrocatalytic activity toward reduction of iodate and V-based
      electrocatalytic activity toward ascorbic acid oxidation, thus acting as a
      versatile multielectrocatalyst. 

PMID- 25603456
TI  - Is expression of rat breast matrix components influenced by estrogen, progestins
      and tibolone?
AB  - AIM: To study the effects of estrogen therapy, alone or combined with
      progestogens, and of tibolone on the expression of heparanase (HSPE),
      extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), perlecan and
      proliferating cell nuclear antigen (PCNA) in normal breast tissue. METHODS:
      Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of
      the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2)
      estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate +
      norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone;
      (6) placebo. Following treatment, the expressions of mRNA for HSPE, MMP-2 and MMP
      9 were analyzed by real-time PCR and the protein expressions of HSPE, MMP-2, MMP
      9, perlecan and PCNA were quantified by immunohistochemistry. RESULTS: There was
      a statistically significant difference among the groups for the expression of
      HSPE mRNA due to high levels in the tibolone group. The groups differed in terms
      of PCNA, with lower levels found in the tibolone group followed by the estradiol
      benzoate + dydrogesterone group. A statistically significant positive correlation
      was observed for PCNA versus perlecan and MMP-9. CONCLUSIONS: There was no
      difference in the effects of combinations of estradiol and different progestogens
      on extracellular matrix components, and breast cell proliferation was associated
      with increases in perlecan and MMP-9.

PMID- 25603458
TI  - Finding and getting what you want when you want it just got easier at
      ANESTHESIOLOGY.

PMID- 25603462
TI  - Statistical thermodynamics of material transport in nonisothermal suspensions.
AB  - An approach to the transport of material in a temperature gradient is outlined
      using nonequilibrium thermodynamics theory. The model is applicable to the
      thermophoresis of colloids and nanoparticles in systems with limited miscibility.
      Component chemical potentials in binary systems are calculated using statistical
      mechanics. The local pressure distribution is obtained using the condition of
      local thermodynamic equilibrium around the suspended particle. The Laplace
      contribution of the local pressure distribution within the layer of liquid
      surrounding the particle leads to a size dependence that is consistent with
      empirical data. The contribution of Keezom interaction to the thermodiffusion
      coefficient is calculated using empirical values of the thermodiffusion
      coefficient for silica particles in water and acetonitrile. The resulting
      interaction energies are consistent with those found in the literature. 

PMID- 25603459
TI  - A novel insulin resistance index to monitor changes in insulin sensitivity and
      glucose tolerance: the ACT NOW study.
AB  - OBJECTIVE: The objective was to test the clinical utility of Quantose M(Q) to
      monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic
      subjects. Quantose M(Q) is derived from fasting measurements of insulin, alpha
      hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose
      metabolites shown to correlate with insulin-stimulated glucose disposal. RESEARCH
      DESIGN AND METHODS: Participants were 428 of the total of 602 ACT NOW impaired
      glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo
      and followed for 2.4 years. At baseline and study end, fasting plasma metabolites
      required for determination of Quantose, glycated hemoglobin, and oral glucose
      tolerance test with frequent plasma insulin and glucose measurements to calculate
      the Matsuda index of insulin sensitivity were obtained. RESULTS: Pioglitazone
      treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence
      interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with
      insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by
      1.45 [3.45] mg.min(-1).kgwbm(-1)) (median [interquartile range]) (P < .001 vs
      placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose
      M(Q) correlated with the Matsuda index at baseline and change in the Matsuda
      index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was
      progressively higher across closeout glucose tolerance status (diabetes, IGT,
      normal glucose tolerance). In logistic models including only anthropometric and
      fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin
      in predicting incident diabetes. CONCLUSIONS: In IGT subjects, Quantose M(Q)
      parallels changes in insulin sensitivity and glucose tolerance with pioglitazone
      therapy. Due to its strong correlation with improved insulin sensitivity and its
      ease of use, Quantose M(Q) may serve as a useful clinical test to identify and
      monitor therapy in insulin-resistant patients.

PMID- 25603461
TI  - Tissue specific regulation of glucocorticoids in severe obesity and the response
      to significant weight loss following bariatric surgery (BARICORT).
AB  - CONTEXT: Tissue cortisol exposure is under the control of the isozymes of 11beta
      hydroxysteroid dehydrogenase (11beta-HSD). 11beta-HSD1 in vivo, acts as an
      oxoreductase converting inactive cortisone to active cortisol. We hypothesized
      that 11beta-HSD1 activity is dysregulated in obesity and alters following
      bariatric surgery induced weight loss in different tissues. METHODS: We recruited
      21 patients prior to undergoing bariatric surgery and performed cortisol
      generation profiles (following oral cortisone administration), urinary
      corticosteroid metabolite analysis, adipose tissue microdialysis, and tissue gene
      expression before and after weight loss, following bariatric surgery. Archived
      tissue samples from 20 previous bariatric surgery patients were also used for
      tissue gene expression studies. RESULTS: Gene expression showed a positive
      correlation with 11beta-HSD1 and BMI in omental adipose tissue (OM) (r = +0.52, P
      = .0001) but not sc adipose tissue (r = +0.28, P = .17). 11beta-HSD1 expression
      in liver negatively correlated with body mass index (BMI) (r = -0.37, P = .04).
      11beta-HSD1 expression in sc adipose tissue was significantly reduced after
      weight loss (0.41 +/- 0.28 vs 0.17 +/- 0.1 arbitrary units, P = .02). Following
      weight loss, serum cortisol generation increased during a cortisol generation
      profile (area under the curve 26 768 +/- 16 880 vs 47 579 +/- 16 086
      nmol/L/minute, P <= .0001.) Urinary corticosteroid metabolites demonstrated a
      significant reduction in total cortisol metabolites after bariatric surgery (15
      224 +/- 6595 vs 8814 +/- 4824 MUg/24 h, P = .01). Microdialysis of sc adipose
      tissue showed a threefold reduction in cortisol/cortisone ratio after weight
      loss. CONCLUSIONS: This study highlights the differences in tissue specific
      regulation of cortisol metabolism in obesity and after weight loss. Following
      bariatric surgery hepatic 11beta-HSD1 activity increases, sc adipose tissue
      11beta-HSD1 activity is reduced and total urinary cortisol metabolites are
      reduced indicating a possible reduction in hypothalamic pituitary adrenal axis
      drive. 11beta-HSD1 expression correlates positively with BMI in omental adipose
      tissue and negatively within hepatic tissue. 11beta-HSD1 expression is reduced in
      sc adipose tissue after weight loss.

PMID- 25603460
TI  - Loss of methylation at GNAS exon A/B is associated with increased intrauterine
      growth.
AB  - CONTEXT: GNAS is one of few genetic loci that undergo allelic-specific
      methylation resulting in the parent-specific expression of at least four
      different transcripts. Due to monoallelic expression, heterozygous GNAS mutations
      affecting either paternally or maternally derived transcripts cause different
      forms of pseudohypoparathyroidism (PHP), including autosomal-dominant PHP type Ib
      (AD-PHP1B) associated with loss of methylation (LOM) at exon A/B alone or
      sporadic PHP1B (sporPHP1B) associated with broad GNAS methylation changes.
      Similar to effects other imprinted genes have on early development, we recently
      observed severe intrauterine growth retardation in newborns, later diagnosed with
      pseudopseudohypoparathyroidism (PPHP) because of paternal GNAS loss-of-function
      mutations. OBJECTIVES: This study aimed to determine whether GNAS methylation
      abnormalities affect intrauterine growth. PATIENTS AND METHODS: Birth parameters
      were collected of patients who later developed sporPHP1B or AD-PHP1B, and of
      their healthy siblings. Comparisons were made to newborns affected by PPHP or
      PHP1A. RESULTS: As newborns, AD-PHP1B patients were bigger than their healthy
      siblings and well above the reference average; increased sizes were particularly
      evident if the mothers were unaffected carriers of STX16 deletions. SporPHP1B
      newborns were slightly above average for weight and length, but their overgrowth
      was less pronounced than that of AD-PHP1B newborns from unaffected mothers.
      CONCLUSION: LOM at GNAS exon A/B due to maternal STX16 deletions and the
      resulting biallelic A/B expression are associated with enhanced fetal growth.
      These findings are distinctly different from those of PPHP patients with paternal
      GNAS exons 2-13 mutations, whose birth parameters are almost 4.5 z-scores below
      those of AD-PHP1B patients born to healthy mothers.

PMID- 25603463
TI  - Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery:
      A pilot study.
AB  - Bone marrow fat may serve a metabolic role distinct from other fat depots, and it
      may be altered by metabolic conditions including diabetes. Caloric restriction
      paradoxically increases marrow fat in mice, and women with anorexia nervosa have
      high marrow fat. The longitudinal effect of weight loss on marrow fat in humans
      is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric
      bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11
      morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow
      fat content (percentage fat fraction) before and 6 months after RYGB using
      magnetic resonance spectroscopy. Total body fat mass declined in all participants
      (mean +/- SD decline 19.1 +/- 6.1 kg or 36.5% +/- 10.9%, p<0.001). Areal bone
      mineral density (BMD) decreased by 5.2% +/- 3.5% and 4.1% +/- 2.6% at the femoral
      neck and total hip, respectively, and volumetric BMD decreased at the spine by
      7.4% +/- 2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by
      diabetes status (adjusted p=0.04). There was little mean change in marrow fat in
      nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast,
      marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05).
      Changes in total body fat mass and marrow fat were inversely correlated among
      nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In
      conclusion, among those without diabetes, marrow fat is maintained on average
      after RYGB, despite dramatic declines in overall fat mass. Among those with
      diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should
      take diabetes status into account. Marrow fat may have unique metabolic behavior
      compared with other fat depots.

PMID- 25603464
TI  - Induction of CXCL2 and CCL2 by pressure force requires IL-1beta-MyD88 axis in
      osteoblasts.
AB  - Mechanical stresses including pressure force induce chemokine expressions in
      osteoblasts resulting in inflammatory reactions and bone remodeling. However, it
      has not been well elucidated how mechanical stresses induce inflammatory
      chemokine expressions in osteoblasts. IL-1beta has been identified as an
      important pathogenic factor in bone loss diseases, such as inflammatory arthritis
      and periodontitis. Myeloid differentiation factor 88 (MyD88) is an essential
      downstream adaptor molecule of IL-1 receptor signaling. This study was to examine
      the gene expression profiles of inflammatory chemokines and the role of MyD88 in
      osteoblasts stimulated by pressure force. Pressure force (10g/cm(2)) induced
      significant mRNA increases of CXCL2, CCL2, and CCL5, as well as prompt
      phosphorylation of MAP kinases (ERK, p38 and JNK), in wild-type primary
      osteoblasts. The CXCL2 and CCL2 mRNA increases and MAP kinase phosphorylation
      were severely impaired in MyD88(-/-) osteoblasts. Constitutive low-level
      expression of IL-1beta mRNA was similarly observed in both wild-type and MyD88(-/
      ) osteoblasts, which was not altered by pressure force stimulation. Notably,
      neutralization of IL-1beta with a specific antibody significantly impaired
      pressure force-induced mRNA increases of CXCL2 and CCL2, as well as MAP kinase
      phosphorylation, in wild-type osteoblasts. Furthermore, pre-treatment with
      recombinant IL-1beta significantly enhanced MAP kinase phosphorylation and mRNA
      increases of CXCL2 and CCL2 by pressure force in wild-type but not MyD88(-/-)
      osteoblasts. These results have suggested that the activation of MyD88 pathway by
      constitutive low-level IL-1beta expression is essential for pressure force
      induced CXCL2 and CCL2 expression in osteoblasts. Thus MyD88 signal in
      osteoblasts may be required for bone resorption by pressure force through
      chemokine induction. 

PMID- 25603466
TI  - Comparison of SAFER behavior assessment results in shelter dogs at intake and
      after a 3-day acclimation period.
AB  - In this study, it was hypothesized that different results would be obtained by
      canine behavior assessments performed within 24 hr of shelter intake (Day 0) and
      after a 3-day acclimation period (Day 3). Safety Assessment for Evaluating
      Rehoming assessments were performed on 33 dogs at 2 municipal shelters.
      Agreements between Day 0 and Day 3 varied among subtests, and no consistent
      temporal patterns were observed. Weighted kappa statistics for each subtest
      ranged from .28 to .78, and percentage discordance was 0% to 18%. In a 2nd
      analysis, subtests skipped due to serious aggression were replaced with scores
      corresponding to serious aggression, and missing values for the Food subtest were
      replaced with scores for no aggression if the dog did not eat. For subtests
      skipped due to severe aggression, more than 50% of the dogs had scores indicating
      low aggression on the other assessment. Eight of 16 dogs who did not eat on Day 0
      ate on Day 3; 2 showed aggression. Until the ideal time to test can be
      identified, it should be based on the individual dog's welfare status, and
      testing of dogs showing severe stress should be avoided.

PMID- 25603465
TI  - Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity.
AB  - Bone fractures remain a serious health burden and prevention and enhanced healing
      of fractures have been obtained by augmenting either BMP or Wnt signaling.
      However, whether BMP and Wnt signaling are both required or are self-sufficient
      for anabolic and fracture healing activities has never been fully elucidated.
      Mice haploinsufficient for Dkk1 (Dkk1(+/-)) exhibit a high bone mass phenotype
      due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2
      expression in the limbs (Bmp2(c/c);Prx1::cre) succumb to spontaneous fracture and
      are unable to initiate fracture healing; combined, these mice offer an
      opportunity to examine the requirement for activated BMP signaling on the
      anabolic and fracture healing activity of Wnts. When Dkk1(+/-) mice were crossed
      with Bmp2(c/c);Prx1::cre mice, the offspring bearing both genetic alterations
      were unable to increase bone mass and heal fractures, indicating that increased
      canonical Wnt signaling is unable to exploit its activity in absence of Bmp2.
      Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic
      activity and that therapies aimed at preventing fractures and fostering fracture
      repair may need to target both pathways for maximal efficacy. 

PMID- 25603467
TI  - Prolonged in vivo administration of testosterone-enanthate, the widely used and
      abused anabolic androgenic steroid, disturbs prolactin and cAMP signaling in
      Leydig cells of adult rats.
AB  - This study was designed to systematically analyze and define the effects of 1
      day, 2-weeks, 10-weeks intramuscular administration of testosterone-enanthate,
      widely used and abused anabolic androgenic steroid (AAS), on main regulators of
      steroidogenesis and steroidogenic genes expression in testosterone-producing
      Leydig cells of adult rats. The results showed that prolonged (10-weeks)
      intramuscular administration of testosterone-enanthate, in clinically relevant
      dose, significantly increased prolactin, but decreased Prlr2 and Gnrhr in
      pituitary of adult rat. The levels of testosterone, Insl3, cAMP and mitochondrial
      membrane potential of Leydig cells were significantly reduced. This was followed
      by decreased expression of some steroidogenic enzymes and regulatory proteins
      such as Lhcgr, Prlr1/2, Tspo, Star, Cyp11a1, Cyp17a1, Dax1. Oppositely, Hsd3b1/2,
      Hsd3b5, Hsd17b4, Ar, Arr19 increased. In the same cells, transcriptional milieu
      of cAMP signaling elements was disturbed with remarkable up-regulation of PRKA
      (the main regulator of steroidogenesis). Increased prolactin together with
      stimulated transcription of Jak2/Jak3 could account for increased Hsd3b1/2 and
      Hsd3b5 in Leydig cells following 10-weeks in vivo treatment with testosterone
      enanthate. In vitro studies revealed that testosterone is capable to increase
      level of Prlr1, Prlr2, Hsd3b1/2, Hsd3b5 in Leydig cells. Accordingly,
      testosterone-induced changes in prolactin receptor signaling together with up
      regulation of PRKA, Hsd3b1/2, Hsd3b5, Ar in Leydig cells, could be the possible
      mechanism that contribute to the establishment of a new adaptive response to
      maintain homeostasis and prevent loss of steroidogenic function. Presented data
      provide new molecular insights into the relationship between disturbed
      testosterone homeostasis and mammalian reproduction and are important in terms of
      wide use and abuse of AASs and human reproductive health. 

PMID- 25603468
TI  - Critical roles of intestinal epithelial vitamin D receptor signaling in
      controlling gut mucosal inflammation.
AB  - Although vitamin D receptor (VDR) is highly expressed in the intestine, the role
      of VDR signaling in the gut is not fully understood. Our recent studies unveil a
      regulatory circuit that centers gut epithelial VDR as a key molecule in the
      control of mucosal inflammation and colitis development. On the one hand,
      intestinal epithelial VDR signaling protects the integrity of the mucosal barrier
      by inhibiting inflammation-induced epithelial cell apoptosis. This barrier
      protecting, anti-colitic activity is independent of the non-epithelial immune VDR
      actions. A healthy and intact mucosal barrier prevents bacterial invasion and
      thus reduces mucosal inflammation. On the other hand, inflammation in turn down
      regulates epithelial VDR expression by inducing VDR-targeting microRNA-346, thus
      compromising mucosal barrier functions. Consistently, colonic epithelial VDR
      levels are markedly reduced in patients with inflammatory bowel diseases or in
      experimental colitis models, whereas vitamin D analog therapy that ameliorates
      colitis up-regulates epithelial VDR. Thus, gut epithelial VDR signaling appears
      to play an essential role in controlling mucosal inflammation and thus could be a
      useful therapeutic target in the management of inflammatory bowel diseases. This
      article is part of a special issue entitled '17th Vitamin D Workshop' . 

PMID- 25603469
TI  - Metal-binding promiscuity in artificial metalloenzyme design.
AB  - This review presents recent examples of metal-binding promiscuity in protein
      scaffolds and highlights the effect of metal variation on catalytic
      functionality. Naturally evolved binding sites, as well as unnatural amino acids
      and cofactors can bind a diverse range of metals, including non-biological
      transition elements. Computational screening and rational design have been
      successfully used to create promiscuous binding-sites. Incorporation of non
      native metals into proteins expands the catalytic range of transformations
      catalysed by enzymes and enhances their potential for application in chemicals
      synthesis. 

PMID- 25603470
TI  - Compartmentalization of incompatible reagents within Pickering emulsion droplets
      for one-pot cascade reactions.
AB  - It is a dream that future synthetic chemistry can mimic living systems to process
      multistep cascade reactions in a one-pot fashion. One of the key challenges is
      the mutual destruction of incompatible or opposing reagents, for example, acid
      and base, oxidants and reductants. A conceptually novel strategy is developed
      here to address this challenge. This strategy is based on a layered Pickering
      emulsion system, which is obtained through lamination of Pickering emulsions. In
      this working Pickering emulsion, the dispersed phase can separately
      compartmentalize the incompatible reagents to avoid their mutual destruction,
      while the continuous phase allows other reagent molecules to diffuse freely to
      access the compartmentalized reagents for chemical reactions. The
      compartmentalization effects and molecular transport ability of the Pickering
      emulsion were investigated. The deacetalization-reduction, deacetalization
      Knoevenagel, deacetalization-Henry and diazotization-iodization cascade reactions
      demonstrate well the versatility and flexibility of our strategy in processing
      the one-pot cascade reactions involving mutually destructive reagents. 

PMID- 25603471
TI  - Let's not, and say we would: imagined and actual responses to witnessing
      homophobia.
AB  - We compared imagined versus actual affective and behavioral responses to
      witnessing a homophobic slur. Participants (N = 72) witnessed a confederate using
      a homophobic slur, imagined the same scenario, or were not exposed to the slur.
      Those who imagined hearing the slur reported significantly higher levels of
      negative affect than those who actually witnessed the slur, and nearly one half
      of them reported that they would confront the slur, whereas no participants who
      actually heard the slur confronted it. These findings reveal a discrepancy
      between imagined and real responses to homophobic remarks, and they have
      implications for the likelihood that heterosexuals will actually confront
      homophobic remarks. 

PMID- 25603472
TI  - Grandparental help in Indonesia is directed preferentially towards needier
      descendants: a potential confounder when exploring grandparental influences on
      child health.
AB  - A considerable body of evidence has now demonstrated positive correlations
      between grandparental presence and child health outcomes. It is typically assumed
      that such correlations exist because grandparental investment in their
      grandchildren improves child health and wellbeing. However, less is known about
      how grandparents allocate help to adult children and grandchildren, particularly
      in lower income contexts. Here we use detailed quantitative data from the
      longitudinal Indonesia Family Life Survey (data collected in 1993, 1997, 2000,
      2007; n = 16,250) to examine grandparental help in a society transitioning both
      demographically and economically. We test the hypothesis that grandparents direct
      help preferentially towards those adult children and grandchildren most in need
      of help. This hypothesis was supported for help provided by married grandparents
      and single grandmothers, who tended to: provide more help to their adult children
      when this generation had young children themselves, provide financial help if
      their adult children were poorer, and provide more household help if their adult
      daughters worked outside the home. One unexpected result was that help from
      maternal and paternal grandparents is positively correlated; if one set of
      grandparents is helping the other set is more likely to help, counter to our
      predictions. These results provide support for the hypothesis that grandparents
      preferentially invest in some descendants over others, where married grandparents
      and single grandmothers tend to invest in those adult children and grandchildren
      with the most need. Investigating the effect of grandparents on child health
      outcomes may therefore be confounded by grandparent's preferential investment in
      needier descendants.

PMID- 25603473
TI  - Fractal dimension of apical dendritic arborization differs in the superficial and
      the deep pyramidal neurons of the rat cerebral neocortex.
AB  - Pyramidal neurons of the mammalian cerebral cortex have specific structure and
      pattern of organization that involves the presence of apical dendrite. Morphology
      of the apical dendrite is well-known, but quantification of its complexity still
      remains open. Fractal analysis has proved to be a valuable method for analyzing
      the complexity of dendrite morphology. The aim of this study was to establish the
      fractal dimension of apical dendrite arborization of pyramidal neurons in
      distinct neocortical laminae by using the modified box-counting method. A total
      of thirty, Golgi impregnated neurons from the rat brain were analyzed: 15
      superficial (cell bodies located within lamina II-III), and 15 deep pyramidal
      neurons (cell bodies situated within lamina V-VI). Analysis of topological
      parameters of apical dendrite arborization showed no statistical differences
      except in total dendritic length (p=0.02), indicating considerable homogeneity
      between the two groups of neurons. On the other hand, average fractal dimension
      of apical dendrite was 1.33+/-0.06 for the superficial and 1.24+/-0.04 for the
      deep cortical neurons, showing statistically significant difference between these
      two groups (p<0.001). In conclusion, according to the fractal dimension values,
      apical dendrites of the superficial pyramidal neurons tend to show higher
      structural complexity compared to the deep ones. 

PMID- 25603475
TI  - The confirmatory factor structure of neurological soft signs in Nigerians with
      first episode schizophrenia.
AB  - We describe empirically derived categories of NSS in first episode schizophrenia
      among indigenous Africans. A total of 84 Nigerian patients with the disease were
      assessed using the neurological evaluation scale. An exploratory factor analysis
      with orthogonal varimax rotation was first conducted and the factors derived
      based on a priori criteria were subjected to confirmatory analyses using SPSS
      18.0 and AMOS 18.0. We tested four different competing models to identify the
      structure with the best fit to the data. The relationship of the derived NSS
      structure with the clinical characteristics of schizophrenia was then explored
      using the Pearson correlation method. The overall clinical status was assessed
      using the positive and negative syndrome scale and clinical global impression.
      Additional assessments included the pre-morbid adjustment scale and calgary
      depression scale for schizophrenia. A three factor structure in which
      stereognosis is prescribed to load into a 'perceptual and motor sequencing'
      category (audio-visual integration, fist-edge palm, rhythm tapping, extinction,
      right-left confusion) provided the best fit to the data (chi-square goodness of
      fit test=1.25; comparative fit index=0.95; root square means error of
      approximation <0.05). The other two factors were: 'eye movement' (synkinesis,
      convergence, gaze impersistence) and 'motor co-ordination and graphaesthesia'
      (Tandem walk, adventitious flow, graphaesthesia). The signs were associated with
      severe negative (r=0.456, p<0.001), and disorganization (r=0.559, p<0.001)
      psychopathologies. NSS in this sample are heterogeneous, but aggregates into
      three correlated categories with significant overlap with previously described
      classifications. 

PMID- 25603474
TI  - Effects of transcranial direct current stimulation on naming and cortical
      excitability in stroke patients with aphasia.
AB  - This study aimed to investigate the effects of anodal transcranial direct current
      stimulation (A-tDCS) over the left posterior perisylvian region (PPR) on picture
      naming and cortical excitability measured with electroencephalography (EEG)
      nonlinear dynamics analysis (NDA) in aphasic patients. Twelve aphasic patients
      received 20 sessions of speech-language therapy during each of three phases: sham
      tDCS (Phase A1); A-tDCS to the left PPR (Phase B); and sham tDCS (Phase A2).
      Picture naming and auditory word-picture identification were measured before and
      after each phase. The EEG nonlinear index of approximate entropy (ApEn) was
      calculated for all subjects and 12 normal controls. Picture naming and auditory
      word-picture identification was significantly improved after phase B. The EEG
      ApEn analysis indicated that improved picture naming correlated with a higher
      activation level in wide areas of the left hemisphere and in isolated areas of
      the right hemisphere after phase B. These results revealed that A-tDCS over the
      left PPR coupled with speech-language therapy can improve picture naming and
      auditory comprehension in aphasic patients. tDCS not only modulates activity in
      the brain region directly underlying the stimulating electrode but also in a
      network of brain regions that are function-related. 

PMID- 25603476
TI  - The C1473G polymorphism in the Tryptophan hydroxylase-2 gene: involvement in
      ethanol-related behavior in mice.
AB  - Tryptophan hydroxylase-2 (Tph2) is the rate limiting enzyme of serotonin
      synthesis in the brain. The functional (C1473G) polymorphism in the mouse Tph2
      gene affecting the enzymatic activity was suspected to be involved in behavioral
      actions of ethanol (EtOH). Congenic B6-1473C (C/C) and B6-1473G (G/G) lines bred
      from C57BL/6 mice were not different in EtOH-induced sleep time and hypothermia.
      B6-1473C mice displayed increased EtOH preference on the second and third days
      compared to that of the first day, but no differences in this parameter was found
      across genotypes. Both lines demonstrated the same responsiveness to hypothermic
      and hypnotic effect of acute EtOH treatment after repeated alcohol exposure.
      However, acute EtOH administration led to reduction of locomotor activity in B6
      1473C, but not in B6-1473G animals and to increase of time spent in the center of
      open-field arena in B6-1473G, but not in B6-1473C mice. Thus, the present study
      indicates the involvement of C1473G polymorphism in mTph2 gene in the regulation
      of EtOH-induced effects on locomotor activity and anxiety-like behavior in mice. 

PMID- 25603477
TI  - Life after hypomethylating agents in myelodysplastic syndrome: new strategies.
AB  - PURPOSE OF REVIEW: Hypomethylating agents, azacitidine and decitabine, are
      successfully used for the treatment of myelodysplastic syndromes (MDS). In spite
      of improvement in survival, MDS is still incurable without hematopoietic stem
      cell transplant, and in case of absence/loss of response to hypomethylating
      agents, outcome is poor. The purpose of this article is to provide an overview of
      the new approach to MDS, elucidate the advancements in understanding factors
      predictive of response to hypomethylating agents, the progress of research to
      better stratify individual patients, and optimize therapeutic choices, the
      availability and efficacy of new drugs. RECENT FINDINGS: The prognostic
      importance of recurrent somatic mutations has been elucidated (i.e., ASXL1, TP53
      and SF3B1 mutations) and the power to predict response to hypomethylating therapy
      ascribed to specific mutations (TET2 mutations). The most challenging agents
      among the numerous evaluated are those with a strong biological background,
      targeting specific molecular alterations (IDH2 mutation) or altered signaling
      pathways. Hematopoietic stem cell transplant remains the only curative option,
      and wider choice of donor (sibling, unrelated, cord blood, haploidentical) and
      different approaches to conditioning renders it feasible for a higher percentage
      of elderly patients with MDS. SUMMARY: Few new molecules have reached phase III,
      the majority being in phase I/II studies. Most importantly, prognostic tools have
      profoundly improved whereas attitude of hematologists is changing rapidly. VIDEO
      ABSTRACT: http://links.lww.com/COH/A9.

PMID- 25603478
TI  - Recent developments in the treatment of older individuals with acute myeloid
      leukemia: 2014.
AB  - PURPOSE OF REVIEW: The treatment of acute myeloid leukemia (AML) in older persons
      remains a tremendous clinical challenge. AML in older patients is more often
      associated with biologically unfavorable features, and these patients are less
      likely to tolerate or accept intensive therapy. There have not been substantial
      improvements in outcome for this group of patients despite decades of research.
      In this review, we summarize the most substantial contributions in the past 2
      years. RECENT FINDINGS: There have been three major research themes in the
      recently published literature for older patients with AML: methods to predict
      response to therapy, models to predict toxicity of therapy in older, less-fit
      patients, and investigation of novel agents for AML patients with either newly
      diagnosed or relapsed disease. An unexpected recent finding has been the
      observation that complete remission in this disease may not necessarily translate
      into an overall survival advantage, and conversely, survival benefit has been
      demonstrated without any improvement in complete remission. SUMMARY: Although
      anthracycline and cytarabine-based therapy remains the standard of care for older
      patients with AML, this option remains suboptimal for the vast majority of
      patients. We argue for a national research agenda that may help to accelerate
      progress for older people with AML.

PMID- 25603479
TI  - A sexually dimorphic corolla appendage affects pollen removal and floral
      longevity in gynodioecious Cyananthus delavayi (Campanulaceae).
AB  - The floral traits of bisexual flowers may evolve in response to selection on both
      male and female functions, but the relative importance of selection associated
      with each of these two aspects is poorly resolved. Sexually dimorphic traits in
      plants with unisexual flowers may reflect gender-specific selection, providing
      opportunities for gaining an increased understanding of the evolution of specific
      floral traits. We examined sexually dimorphic patterns of floral traits in
      perfect and female flowers of the gynodioecious species Cyananthus delavayi. A
      special corolla appendage, the throat hair, was investigated experimentally to
      examine its influences on male and female function. We found that perfect flowers
      have larger corollas and much longer throat hairs than female flowers, while
      female ones have much exerted stigmas. The presence of throat hairs prolonged the
      duration of pollen presentation by restricting the amount of pollen removed by
      pollen-collecting bees during each visit. Floral longevity was negatively related
      to the rate of pollen removal. When pollen removal rate was limited in perfect
      flowers, the duration of the female phases diminished with the increased male
      phase duration. There was a weak negative correlation between throat hair length
      and seed number per fruit in female flowers, but this correlation was not
      significant in perfect flowers. These results suggest that throat hairs may
      enhance male function in terms of prolonged pollen presentation. However, throat
      hairs have no obvious effect on female function in terms of seed number per
      fruit. The marked sexual dimorphism of this corolla appendage in C. delavayi is
      likely to have evolved and been maintained by gender-specific selection. 

PMID- 25603480
TI  - Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the
      diagnosis of acute pyelonephritis in children.
AB  - BACKGROUND: In children with urinary tract infection (UTI), only those with
      pyelonephritis (and not cystitis) are at risk for developing long-term renal
      sequelae. If non-invasive biomarkers could accurately differentiate children with
      cystitis from children with pyelonephritis, treatment and follow-up could
      potentially be individualized. OBJECTIVES: The objectives of this review were to
      1) determine whether procalcitonin, C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic
      evaluation of children with UTI; 2) assess the influence of patient and study
      characteristics on the diagnostic accuracy of these tests, and 3) compare the
      performance of the three tests to each other. SEARCH METHODS: We searched
      MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews for this review. The
      reference lists of all included articles and relevant systematic reviews were
      searched to identify additional studies not found through the electronic search.
      SELECTION CRITERIA: We only considered published studies that evaluated the
      results of an index test (procalcitonin, CRP, ESR) against the results of an
      acute-phase DMSA scan (conducted within 30 days of the UTI) in children aged 0 to
      18 years with a culture-confirmed episode of UTI. The following cutoff values
      were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP
      and 30 mm/h for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently
      applied the selection criteria to all citations and independently abstracted
      data. We used the bivariate model to calculate pooled random-effects pooled
      sensitivity and specificity values. MAIN RESULTS: A total of 24 studies met our
      inclusion criteria. Seventeen studies provided data for the primary analysis: six
      studies (434 children) included data on procalcitonin, 13 studies (1638 children)
      included data on CRP, and six studies (1737 children) included data on ESR (some
      studies had data on more than one test). The summary sensitivity estimates (95%
      CI) for the procalcitonin, CRP, ESR tests at the aforementioned cutoffs were 0.86
      (0.72 to 0.93), 0.94 (0.85 to 0.97), and 0.87 (0.77 to 0.93), respectively. The
      summary specificity values for procalcitonin, CRP, and ESR tests at these cutoffs
      were 0.74 (0.55 to 0.87), 0.39 (0.23 to 0.58), and 0.48 (0.33 to 0.64),
      respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be
      sufficiently accurate to be helpful in differentiating children with cystitis
      from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be
      somewhat useful in ruling out pyelonephritis (decreasing the probability of
      pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us
      from making recommendations at this time. The procalcitonin test seems better
      suited for ruling in pyelonephritis, but the limited number of studies and the
      marked heterogeneity between studies prevents us from reaching definitive
      conclusions. Thus, at present, we do not find any compelling evidence to
      recommend the routine use of any of these tests in clinical practice.

PMID- 25603481
TI  - Pressure Makes Pleasure: A Preliminary Study of Increasing Irrigation Pressure of
      Flexible Cystoscopy Improves Male Patient Comfort by an Easy Way.
AB  - OBJECTIVE: To evaluate the impact of increasing irrigation pressure when
      performing flexible cystoscopy for male patients on visual analog scale pain
      scores. PATIENTS AND METHODS: A total of 168 male patients admitted to our clinic
      for flexile cystoscopy by the same urologist between March 2011 and December 2012
      were randomized to three equal groups, each of which had 56 patients. Different
      irrigation pressures were easily achieved by adjusting the height of irrigation
      solution bag (1000 mL of 0.9% saline). The height difference between the bag and
      the bed (for cystoscopy) of group 1, 2, and 3 was 80, 100, and 150 cm,
      respectively. All patients received 10 mL lidocaine gel for 3 minutes for local
      anesthesia before flexible cystoscopy. Patients' pain feeling was recorded on a
      visual analog scale (VAS) ranging from 0 to 10 after the cystoscopy. The duration
      of the procedure for each patient was also recorded. RESULTS: The mean pain score
      on VAS was 2.95+/-1.31, 2.48+/-1.26, and 1.66+/-1.00 in group 1, 2, and 3,
      respectively. Compared to group 1 and 2, the mean pain score was significantly
      lower in group 3 (p<0.001, Mann-Whitney U-test), and the mean pain score in group
      2 was statistically significantly lower than that in group 1 (p=0.045, Mann
      Whitney U-test). Patients who were with high irrigation pressure experienced less
      discomfort at cystoscopy. Patient age and duration of the procedure for each
      group were comparable. CONCLUSION: Achieving higher irrigation pressure for
      flexible cystoscopy by adjusting the height of irrigation solution bag improves
      male patients' comfort. It is recommended for male patients.

PMID- 25603482
TI  - Discovery of highly potent, selective, and efficacious small molecule inhibitors
      of ERK1/2.
AB  - Using structure-based design, a novel series of pyridone ERK1/2 inhibitors was
      developed. Optimization led to the identification of (S)-14k, a potent,
      selective, and orally bioavailable agent that inhibited tumor growth in mouse
      xenograft models. On the basis of its in vivo efficacy and preliminary safety
      profiles, (S)-14k was selected for further preclinical evaluation. 

PMID- 25603483
TI  - Hybrid resection of a giant thigh plexiform neurofibroma.
AB  - PRESENTATION OF CASE: Authors present a case of a 55 year old patient with Type 1
      neurofibromatosis (NF1) and a very large right thigh plexiform neurofibroma. The
      patient had increasing difficulty with mobilization due to this enlarging bulky
      mass. Preoperative embolization reduced the bleeding risk at surgery allowing
      successful gross resection of the mass by a multidisciplinary surgical team. Limb
      function was restored to normal. DISCUSSION: Massive plexiform neurofibromatosis
      is a rare expression of von Recklinghausen's disease or NF1. These large masses
      result in severe disfigurement and significant functional disability. They are
      extremely vascular and there is potential for malignant transformation.
      CONCLUSION: These massive tumors require complex preoperative, intraoperative and
      postoperative management strategies with involvement from a multidisplinary team.
      We discuss the challenges of surgical intervention and to discuss the current
      literature.

PMID- 25603484
TI  - A unique complication of radiofrequency therapy to the tongue base.
AB  - INTRODUCTION: Radiofrequency ablation treatment of the tongue base can be used
      either alone or as part of a multilevel approach in the treatment of snoring.
      This involves the generation of thermal energy around the circumvallate papillae
      of the tongue. Potential complications include ulceration, dysphagia, haematoma
      and abscess formation. PRESENTATION OF CASE: We present the case of a 50-year-old
      patient who developed an anterior neck swelling following a second application of
      radiofrequency ablation therapy to the tongue base for snoring. This was
      secondary to an infection of a previously undiagnosed thyroglossal cyst. The
      patient made a full recovery following intravenous antibiotic therapy and
      ultrasound-guided needle aspiration. DISCUSSION: Thyroglossal tract remnants are
      thought to be present in seven percent of the adult population. An infection in a
      thyroglossal tract cyst has not previously been reported following radiofrequency
      ablation of the tongue base. Given the relatively high complication rate of
      tongue base radiofrequency ablation in some series, this complication may be
      under-recognised. CONCLUSION: An infected thyroglossal tract cyst should be
      suspected in patients with anterior neck swellings following radiofrequency
      ablation therapy to the tongue base. We advise caution when performing this
      procedure on patients with known thyroglossal tract remnants though there is
      insufficient evidence to suggest that this procedure is contraindicated.

PMID- 25603485
TI  - Early MRI and intraoperative findings in rapidly destructive osteoarthritis of
      the hip: A case report.
AB  - INTRODUCTION: The pathophysiology of rapidly destructive hip osteoarthritis (OA)
      of the hip is still unclear. Also, there have been only few reports on the
      initial stage of the disease. We report a case of an initial-stage rapidly
      destructive hip OA, documented by magnetic resonance imaging and intraoperative
      findings. PRESENTATION OF CASE: A 77-year-old woman reported left hip pain
      without any antecedent trauma. Initial radiographs showed no obvious abnormality.
      After 4 months of conservative therapy, radiographs showed progressive joint
      space narrowing and T1-weighted magnetic resonance images revealed a bone-marrow
      edema pattern not only on the femoral head but also on the lateral side of the
      acetabulum. Then during total hip arthroplasty, we found extensive inversion of
      the anterosuperior portion of the acetabular labrum, and the location was mostly
      consistent with the bone-marrow edema lesions in the femoral head and acetabulum.
      DISCUSSION: Several theories for the etiology of rapidly destructive hip OA have
      been proposed, including idiopathic chondrolysis, abnormal immunoreaction, intra
      articular deposition of hydroxyapatite crystals, and subchondral insufficiency
      fracture. One of the reasons rapidly destructive hip OA is still considered
      idiopathic is the lack of reports regarding the initial stage of the disease. Our
      report is the first to demonstrate magnetic resonance imaging for initial-stage
      disease with intraoperative findings before collapse of the femoral head.
      CONCLUSION: Inversion of the acetabular labrum may be a mechanism of rapidly
      destructive hip OA.

PMID- 25603486
TI  - False teeth in an apple core: Unusual presentation of a colorectal carcinoma.
AB  - INTRODUCTION: Ingestion of foreign bodies is common amongst the elderly. Although
      most foreign bodies pass through the gastrointestinal tract without consequence
      some cause complications including bowel perforation. PRESENTATION OF CASE: We
      present a case of denture ingestion that lead to the diagnosis of an unsuspected
      colorectal cancer. The patient underwent radical surgery to remove the tumor and
      the ingested denture. The operation and recovery were uneventful. DISCUSSION:
      Complications from ingested foreign bodies mostly occur at points of anatomical
      intestinal tapering. However, tumors of the gastro-intestinal tract can also lead
      to obstructions and other complications. As the incidence of tumors increases
      with age, this possibility should be considered in the differential diagnosis of
      unusual situation. CONCLUSION: Although impaction of a foreign body in a gastro
      intestinal tumor is very rare, our case suggests close follow-up is prudent in
      the elderly should a foreign body be ingested.

PMID- 25603487
TI  - HER2/neu negative salivary duct carcinoma of parotid: A case with forty months
      recurrence free follow up.
AB  - INTRODUCTION: Salivary duct carcinoma (SDC) is very rare, only 1-3% of all
      salivary gland tumors are reported as SDC. SDC predominantly occurs in elderly
      males, SCD is characterized by an aggressive clinical course of the disease with
      less than 60% five years survival from the day of initial diagnosis, lymph node
      metastasis and facial nerve involvement is common, the current literature lacks
      protocol regarding management of this entity and the advantage of adjuvant
      therapy has not been evaluated due to its rare occurrence. PRESENTATION OF CASE:
      We report patient with stage IV HER2/neu negative SDC successfully treated with
      surgery followed by adjuvant radiotherapy, patient is followed up for 40 months
      without evidence of recurrence or metastasis. DISCUSSION: SDC is reported to be
      similar to mammary duct carcinoma in clinical and immunohistologic typing,
      further it shows an association of expression of HER-2/neu and p53, with early
      local disease recurrence, distant metastasis and survival, however; current case
      was adequately followed up and reevaluated after 26 months, MRI did not show
      evidence of recurrence. CONCLUSION: SDC is a rare tumor and information on
      association of HER2/neu with survival is useful in further research on this
      tumor.

PMID- 25603488
TI  - The phantom leaf effect: a replication, part 1.
AB  - OBJECTIVES: To replicate the phantom leaf effect and demonstrate a possible means
      to directly observe properties of the biological field. DESIGN: Thirty percent to
      60% of plant leaves were amputated, and the remaining leaf sections were
      photographed with corona discharge imaging. All leaves were cut before placement
      on film. A total of 137 leaves were used. SUBJECTS: Plant leaves of 14 different
      species. RESULTS: Ninety-six phantom leaf specimens were successfully obtained;
      41 specimens did not yield the phantom leaf effect. CONCLUSIONS: A normally
      undetected phantom "structure," possibly evidence of the biological field, can
      persist in the area of an amputated leaf section, and corona discharge can occur
      from this invisible structure. This protocol may suggest a testable method to
      study properties of conductivity and other parameters through direct observation
      of the complete biological field in plant leaves, with broad implications for
      biology and physics.

PMID- 25603489
TI  - Prenatal protein level impacts homing behavior in Long-Evans rat pups.
AB  - OBJECTIVE: This study assessed the effect of varying prenatal protein levels on
      the development of homing behavior in rat pups. METHODS: Long-Evans rats were fed
      one of the four isocaloric diets containing 6% (n = 7 litters), 12% (n = 9), 18%
      (n = 9), or 25% (n = 10) casein prior to mating and throughout pregnancy. At
      birth, litters were fostered to well-nourished control mothers fed a 25% casein
      diet during pregnancy, and an adequate protein diet (25% casein) was provided to
      weaning. On postnatal days 5, 7, 9, 11, and 13, homing behaviors, including
      activity levels, rate of successful returns to the nest quadrant and latencies to
      reach the nest over a 3-minute test period were recorded from two starting
      positions in the home cage. Adult body and brain weights were obtained at
      sacrifice (postnatal day 130 or 200). RESULTS: Growth was impaired in pups whose
      mothers were fed a 6% or, to a lesser extent, a 12% casein diet relative to pups
      whose mothers were fed the 18 and 25% casein diets. The 6 and 12% prenatal
      protein levels resulted in lower activity levels, with the greatest reduction on
      postnatal day 13. However, only the 6% pups had reduced success and higher
      latencies in reaching the nest quadrant when compared with pups from the three
      other nutrition groups. Latency in reaching the nest quadrant was significantly
      and negatively associated with adult brain weight. DISCUSSION: Home orientation
      is a sensitive measure of developmental deficits associated with variations in
      prenatal protein levels, including levels of protein deficiency that do not lead
      to overt growth failure.

PMID- 25603490
TI  - Artery buckling affects the mechanical stress in atherosclerotic plaques.
AB  - BACKGROUND: Tortuous arteries are often seen in patients with hypertension and
      atherosclerosis. While the mechanical stress in atherosclerotic plaque under
      lumen pressure has been studied extensively, the mechanical stability of
      atherosclerotic arteries and subsequent effect on the plaque stress remain
      unknown. To this end, we investigated the buckling and post-buckling behavior of
      model stenotic coronary arteries with symmetric and asymmetric plaque. METHODS:
      Buckling analysis for a model coronary artery with symmetric and asymmetric
      plaque was conducted using finite element analysis based on the dimensions and
      nonlinear anisotropic materials properties reported in the literature. RESULTS:
      Artery with asymmetric plaque had lower critical buckling pressure compared to
      the artery with symmetric plaque and control artery. Buckling increased the peak
      stress in the plaque and led to the development of a high stress concentration in
      artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis
      increased the critical buckling pressure of the artery with asymmetric plaque.
      CONCLUSIONS: Arteries with atherosclerotic plaques are prone to mechanical
      buckling which leads to a high stress concentration in the plaques that can
      possibly make the plaques prone to rupture.

PMID- 25603491
TI  - Dynamics of Hyperbranched Polymers under Confinement: A Dielectric Relaxation
      Study.
AB  - The effect of severe confinement on the dynamics of three different generations
      of hyperbranched polyesters of the Boltorn family is investigated by dielectric
      relaxation spectroscopy (DRS). The polymer chains are intercalated within the
      galleries of natural montmorillonite (Na+-MMT), thus forming 1 nm polymer films
      confined between solid walls. The structure of the nanocomposites is studied with
      X-ray diffraction and the thermal behavior of the polymers in bulk and under
      confinement is determined by differential scanning calorimetry. The glass
      transition temperatures of the polymers show a clear dependence on the generation
      whereas the transition is completely suppressed when all the polymer chains are
      intercalated. The dynamic investigation of the bulk polymers reveals two sub-Tg
      processes, with similar behavior for the three polymers with the segmental
      relaxation observed above the Tg of each polymer. For the nanocomposites, where
      all the polymer chains are severely confined, the dynamics show significant
      differences compared to that of the bulk polymers. The sub-Tg processes are
      similar for the three generations but significantly faster and with weaker
      temperature dependence than those in the bulk. The segmental process appears at
      temperatures below the bulk polymer Tg, it exhibits an Arrhenius temperature
      dependence and shows differences for the three generations. A slow process that
      appears at higher temperatures is due to interfacial polarization.

PMID- 25603492
TI  - Daily chlorhexidine bathing for critically ill patients: a note of caution.

PMID- 25603493
TI  - Three New Dimers and Two Monomers of Phenolic Amides from the Fruits of Lycium
      barbarum and Their Antioxidant Activities.
AB  - The aims of this study were to complement the current knowledge on the
      antioxidative composition of alcohol extracts from the fruits of Lycium barbarum
      and to evaluate their antioxidant activities. Three new dimers of phenolic
      amides, named lyciumamides A (3), B (4), and C (5), together with two monomers, N
      E-coumaroyl tyramine (1) and N-E-feruloyl tyramine (2), were isolated from the
      fruits for the first time with the help of activity-guided chromatography.
      Compounds 1-5 were evaluated for their antioxidant activities in scavenging 2,2
      diphenyl-1-picrylhydrazyl free radical and inhibiting lipid peroxidation in rat
      liver microsomes induced by ascorbate/Fe2+, cumine hydroperoxide, or CCl4/reduced
      form of nicotinamide-adenine dinucleotide phosphate, and the results showed that
      all of them exhibited strong activities, whereas compounds 1 and 2 were more
      potent than the reference tert-butyl-4-hydroxyanisole.

PMID- 25603494
TI  - Associations Between Human Values and Alcohol Consumption Among Norwegians in the
      Second Half of Life.
AB  - Previous studies investigating human values and alcohol consumption have focused
      on adolescents, so the current study examined associations between human values
      and alcohol consumption in a cohort of Norwegians in the second half of life (40
      years and above). Human values were studied within Schwartz' theory.(1) A survey
      was conducted in 2002/2003 among Norwegians aged 40 to 79 years (n = 4 149). The
      respondents completed measures of human values, drinking frequency and typical
      drinking quantity. Females (9%) were more likely to report abstinence than males
      (3%). Males also reported a higher consumption level. Individuals with high
      education had lower levels of abstinence (4%) than those with basic education
      (7%), and high education was also related to more consumption. People aged 40-60
      years were less likely to abstain from alcohol (3%) than individuals aged 61
      years and above (10%). Unmarried individuals were more likely to report
      abstinence, but also reported somewhat higher consumption than married
      individuals. Multivariate analyses adjusting for demographics as well as somatic
      and mental health showed that hedonistic values were related to lower probability
      of abstaining, while Conformity and Universalism values were associated with a
      higher probability of abstaining. Achivement and Hedonism values were associated
      with more alcohol consumption, whereas Universialism, Tradition, and Conformity
      were related to lower alcohol consumption.

PMID- 25603495
TI  - Exploration of a crack use setting and its impact on drug users' risky drug use
      and sexual behaviors: the case of piaules in a Montreal neighborhood.
AB  - From July 2011, a one-year study based on ethnographic methodology was carried
      out in "crack houses" in the neighborhood of Hochelaga-Maisonneuve in Montreal,
      Canada. The study aimed to explore the operational style of a specific indoor
      drug use setting and its impact on users' risky sexual and drug use behaviors in
      a context of drug market change. A thematic analysis of observational and
      interview notes was conducted. This study stresses the importance to examine the
      role of environmental factors in relation to crack smoking's health-related risks
      and to complement individual-based interventions with structural strategies. The
      study's limitations are noted. 

PMID- 25603496
TI  - Visual fatigue caused by watching 3DTV: an fMRI study.
AB  - The objective of this study is to observe the visual fatigue caused by watching
      3DTV using the method of functional magnetic resonance imaging (fMRI). The data
      of fMRI during three kinds of visual stimulation tasks were obtained from twenty
      subjects. At first, blood-oxygen-level dependent (BOLD) signal changes during
      stimuli of checkerboard task were compared before and after one-hour watching
      3D/2DTV, and subjective evaluation was conducted based on the questionnaire
      simultaneously. Then 3D and 2D images were used to stimulate healthy individuals
      to measure brain activities that correlated with stereoscopic vision. Finally,
      the relationship between front or back depth of field images and visual fatigue
      was investigated. The results reveal that the 3D group shows more significant
      differences of brain activities in BA8, BA17, BA18 and BA19 than the 2D group
      during the checkerboard stimulation. BA5, BA6, BA7 and BA8 were testified to have
      close relationship with stereoscopic perception via the 2D/3D images stimulation.
      Furthermore, the front depth of field image was proven to impose a more serious
      impact on visual fatigue than the back one. These conclusions are useful for
      healthy and reasonable 3DTV watching as well as properly designing of 3D scenes. 

PMID- 25603498
TI  - Reaction mechanism of cytochrome c oxidase.

PMID- 25603497
TI  - Practice change toward better adherence to evidence-based treatment of early
      dental decay in the National Dental PBRN.
AB  - BACKGROUND: Significant national investments have aided the development of
      practice-based research networks (PBRNs) in both medicine and dentistry. Little
      evidence has examined the translational impact of these efforts and whether PBRN
      involvement corresponds to better adoption of best available evidence. This study
      addresses that gap in knowledge and examines changes in early dental decay among
      PBRN participants and non-participants with access to the same evidence-based
      guideline. This study examines the following questions regarding PBRN
      participation: are practice patterns of providers with PBRN engagement in greater
      concordance with current evidence? Does provider participation in a PBRNs
      increase concordance with current evidence? Do providers who participate in PBRN
      activities disseminate knowledge to their colleagues? METHODS: Logistic
      regression models adjusting for clustering at the clinic and provider levels
      compared restoration (dental fillings) rates from 2005-2011 among 35 providers in
      a large staff model practice. All new codes for early-stage caries (dental decay)
      and co-occurring caries were identified. Treatment was determined by codes
      occurring up to 6 months following the date of diagnosis. Provider PBRN
      engagement was determined by study involvement and meeting attendance. RESULTS:
      In 2005, restoration rates were high (79.5%), decreased to 47.6% by 2011 (p <
      .01), and differed by level of PBRN engagement. In 2005, engaged providers were
      less likely to use restorations compared to the unengaged (73.1% versus 88.2%; p
      < .01). Providers with high PBRN involvement decreased use of restorations by
      15.4% from 2005 to 2008 (2005: 73%, 2008: 63%; p < .01). Providers with no PBRN
      involvement decreased use by only 7.5% (2005: 88%, 2008: 82%; p = .041). During
      the latter half of 2008 following the May PBRN meeting, attendees reduced
      restorations by 7.5%, compared to a 2.4% among non-attendees (OR = .64, p < .01).
      CONCLUSIONS: Based on actual clinical data, PBRN engagement was associated with
      practice change consistent with current evidence on treatment of early dental
      decay. The impact of PBRN engagement was most significant for the most-engaged
      providers and consistent with a spillover effect onto same-clinic providers who
      were not PBRN-engaged. PBRNs can generate relevant evidence and expedite
      translation into practice.

PMID- 25603499
TI  - Energy and molecules from photochemical/photocatalytic reactions. An overview.
AB  - Photocatalytic reactions have been defined as those processes that require both a
      (not consumed) catalyst and light. A previous definition was whether such
      reactions brought a system towards or away from the (thermal) equilibrium. This
      consideration brings in the question whether a part of the photon energy is
      incorporated into the photochemical reaction products. Data are provided for
      representative organic reactions involving or not molecular catalysts and show
      that energy storage occurs only when a heavily strained structure is generated,
      and in that case only a minor part of photon energy is actually stored (DeltaG up
      to 25 kcal.mol-1). The green role of photochemistry/photocatalysis is rather that
      of forming highly reactive intermediates under mild conditions. 

PMID- 25603500
TI  - New sesquiterpenoids and a diterpenoid from Alpinia oxyphylla.
AB  - The new compounds 2-methyl-6-isopropyl-7-hydroxymethyl naphthalene (1),
      oxyphyllenone H (2), epi-oxyphyllenone (6), (E)-labda-12,14-dien-15(16)-olide-17
      oic acid (3), and two new natural products 4 and 5 were isolated from the ethyl
      acetate part of 95% ethanol extract of Alpinia oxyphylla, together with six known
      compounds 7-12. The inhibitory effects of compounds 1-12 on alpha-glucosidase
      were evaluated, and compounds 1, 3 and 6 showed moderate bioactive effect, with
      inhibitory rates of 10.3%, 10.0% and 11.5%, respectively, compared to the
      positive control acarbose (41.9%) at 20 ug/mL. 

PMID- 25603501
TI  - Comparative pharmacokinetics of hypaconitine after oral administration of pure
      hypaconitine, Aconitum carmichaelii extract and Sini Decoction to rats.
AB  - Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii
      (AC), which is considered to be effective on cardiovascular disease, although it
      also has high toxicity. Sini Decoction (SND), composed of Aconitum carmichaelii,
      Glycyrrhiza uralensis and Zingiber officinale, is a traditional Chinese multi
      herbal formula for recuperating the depleted yang. The aim of this study was to
      compare the pharmacokinetics of HC in rat plasma after oral administration of HC,
      AC extract and SND, and investigate the effect of other two herbal ingredients on
      absorption, metabolism and elimination of HC. A sensitive and specific LC-MS/MS
      method was developed to determine HC in rat plasma. Eighteen male Sprague-Dawley
      rats were randomly assigned to three groups: HC, AC and SND group. Plasma
      concentrations of HC were determined at designated points after oral
      administration, and main pharmacokinetic parameters were estimated. It was found
      that there was obvious difference (p < 0.05) on the pharmacokinetic parameters
      among three groups. Compared with AC group, Tmax, Cmax, k, AUC(0-24) and AUC(0
      infinity) decreased in SND group, while t1/2 and MRT had been lengthened, which
      indicated that the ingredients in other two herbs could influence the
      pharmacokinetic behavior of HC. 

PMID- 25603502
TI  - Cytotoxic activity and composition of petroleum ether extract from Magydaris
      tomentosa (Desf.) W. D. J. Koch (Apiaceae).
AB  - The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch
      has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as
      xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as
      7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The
      antiproliferative activity of Magydaris tomentosa flower extract has been
      evaluated in vitro on murine monocye/macrophages (J774A.1), human melanoma (A375)
      and human breast cancer (MCF-7) tumor cell lines, showing a major activity
      against the latter. 

PMID- 25603504
TI  - A rare cause of dysphagia: compression of esophagus by a giant thoracic spine
      osteophyte.

PMID- 25603505
TI  - Pancreatic peripheral primitive neuroectodermal tumor diagnosed by endoscopic
      ultrasound.

PMID- 25603503
TI  - Structure-guided design of selective Epac1 and Epac2 agonists.
AB  - The second messenger cAMP is known to augment glucose-induced insulin secretion.
      However, its downstream targets in pancreatic beta-cells have not been
      unequivocally determined. Therefore, we designed cAMP analogues by a structure
      guided approach that act as Epac2-selective agonists both in vitro and in vivo.
      These analogues activate Epac2 about two orders of magnitude more potently than
      cAMP. The high potency arises from increased affinity as well as increased
      maximal activation. Crystallographic studies demonstrate that this is due to
      unique interactions. At least one of the Epac2-specific agonists, Sp-8-BnT-cAMPS
      (S-220), enhances glucose-induced insulin secretion in human pancreatic cells.
      Selective targeting of Epac2 is thus proven possible and may be an option in
      diabetes treatment. 

PMID- 25603506
TI  - Salvage peroral endoscopic myotomy for esophageal diverticulum.

PMID- 25603507
TI  - In vivo imaging of duodenal follicular lymphoma with confocal laser
      endomicroscopy.

PMID- 25603508
TI  - Application of polyglycolic acid sheets for delayed perforation after endoscopic
      submucosal dissection of early gastric cancer.

PMID- 25603510
TI  - Sclerotherapy-associated esophageal hematoma in a patient with myelofibrosis and
      portal hypertension.

PMID- 25603509
TI  - Diminutive submucosally invasive cancers of the colon and rectum.

PMID- 25603511
TI  - Salvage hemostasis by scope compression during rectal endoscopic submucosal
      dissection.

PMID- 25603512
TI  - Successful treatment of Boerhaave syndrome with an over-the-scope clip.

PMID- 25603513
TI  - Retroperitoneal fibrosis with a complex cystic lesion mimicking an inferior vena
      cava tumor.

PMID- 25603514
TI  - Massive hemorrhage caused by failure of elastic band release during endoscopic
      variceal ligation.

PMID- 25603515
TI  - Esophageal tuberculosis initially misdiagnosed by endoscopy as a submucosal
      tumor.

PMID- 25603516
TI  - Computed tomography-guided endoscopic recanalization of a completely obstructed
      rectal anastomosis.

PMID- 25603517
TI  - Successful use of a fully covered metal stent for refractory bleeding from a
      duodenal cancer.

PMID- 25603518
TI  - Acute pancreatitis induced by vegetable fibers.

PMID- 25603519
TI  - A new method for endoscopic variceal band ligation in Zenker's diverticulum.

PMID- 25603520
TI  - Polyglycolic acid sheets for repair of refractory esophageal fistula.

PMID- 25603521
TI  - Double-balloon enteroscopy for the detection of diffuse small-bowel polypoid
      ganglioneuromatosis mimicking Crohn's disease in a patient with von
      Recklinghausen disease.

PMID- 25603522
TI  - Endoscopic ultrasound-guided pancreaticojejunostomy with a forward-viewing
      echoendoscope as a treatment for stenotic pancreaticojejunal anastomosis.

PMID- 25603523
TI  - Direct peroral ultraslim endoscopy-guided biliary drainage in a patient with
      cystic duct carcinoma and an occluded self-expandable metallic stent.

PMID- 25603524
TI  - Late presentation of capsule endoscope aspiration with successful extraction by
      flexible bronchoscopy utilizing a snare wire loop.

PMID- 25603525
TI  - Drug-induced small-bowel mucosal atrophy.

PMID- 25603526
TI  - Menetrier's disease with normal albumin level.

PMID- 25603527
TI  - Biogas production improvement and C/N control by natural clinoptilolite addition
      into anaerobic co-digestion of Phragmites australis, feces and kitchen waste.
AB  - Anaerobic co-digestion (A co-D) performance of Phragmites australis, feces and
      kitchen waste with addition of clinoptilolite (one main kind of zeolite) was
      investigated to evaluate the improvement of biogas/methane production and
      internal mechanism of nitrogen and organics control. A better biogas/methane
      production was observed by 10% clinoptilolite (v/v) than bentonite and diatomite,
      with the shortest lag phase of 0.070d(-1), the max rate of 15.89L/(kgVSday) and
      ultimate biogas production of 308.2L/kgVS as the modified Gompertz equation
      predicted. Accordingly, the content of methane in the biogas was increased from
      44.10% to 65.30%. Furthermore, the clinoptilolite inhibited the acidification of
      digestion liquid (optimum pH 7.0-7.5) and enhanced the VFAs (acetic acid,
      propionic acid and butyric acid) destruction. Moreover, 10% of clinoptilolite
      optimally enhanced the microbial utilization of Ca(2+)/Mg(2+), controlled the C/N
      ratio, and improved the biogas production as well as NH3-N/NO3-N inhibition
      efficiency. 

PMID- 25603528
TI  - Effect of acclimatization on hexavalent chromium reduction in a biocathode
      microbial fuel cell.
AB  - A simple acclimatization method for the reduction of hexavalent chromium (Cr(VI))
      at a biocathode by first enriching an exoelectrogenic biofilm on a microbial fuel
      cell (MFC) anode, followed by direct inversion of the anode to function as the
      biocathode, has been established. This novel method significantly enhanced the
      Cr(VI) reduction efficiency of the MFC, which was mainly attributed to the higher
      microbial density and less resistive Cr(III) precipitates on the cathode when
      compared with a common biocathode acclimatization method (control). The
      biocathode acclimatization period was shortened by 19days and the Cr(VI)
      reduction rate was increased by a factor of 2.9. Microbial community analyses of
      biocathodes acclimatized using different methods further verified the feasibility
      of this electrode inversion method, indicating similar dominant bacteria species
      in biofilms, which mainly consist of Gamma-proteobacteria and Bacteria. 

PMID- 25603529
TI  - Biotransformation of 2,4-dinitrotoluene by obligate marine Shewanella marisflavi
      EP1 under anaerobic conditions.
AB  - Anaerobic transformation of 2,4-DNT by obligate marine Shewanella marisflavi EP1
      was investigated. The cell growth of EP1 was proportional to the total amount of
      2,4-DNT reduced. The eventual transformation product was 2,4-diaminotoluene, via
      2-amino-4-nitrotoluene and 4-amino-2-nitrotoluene as intermediates. The presence
      of Cu(2+), dicumarol, metyrapone and flavins intensively influenced the reduction
      activity of 2,4-DNT, suggesting that dehydrogenease, menaquinone, cytochromes and
      flavins are essentially involved in electron transport process for 2,4-DNT
      reduction. These results indicate that biotransformation of 2,4-DNT by EP1 is a
      form of microbial anaerobic respiration. Furthermore, EP1 was capable of
      transforming 2,4-DNT at relatively alkaline range of pH (7-9), and at a wide
      range of temperature (4-40 degrees C) and salinity (2-8% NaCl concentration). Our
      findings not only deepen our understanding of the environmental fate of 2,4-DNT,
      but also provide an extension to the application of shewanellae in the site
      bioremediation and/or wastewater treatment. 

PMID- 25603530
TI  - Development of an oven drying protocol to improve biodiesel production for an
      indigenous chlorophycean microalga Scenedesmus sp.
AB  - Drying of wet algal biomass is a major bottleneck in viable commercial production
      of the microalgal biodiesel. In the present investigation, an oven drying
      protocol was standardized for drying of wet Scenedesmus biomass at 60, 80 and 100
      degrees C with initial sample thickness of 5.0, 7.5 and 10.0mm. The optimum
      drying temperature was found to be 80 degrees C with a maximum lipid yield of
      425.0+/-5.9mgg(-1) at 15h drying time for 5.0mm thick samples with 0.033kWh power
      consumption. Partial drying at 80 degrees C up to 10% residual moisture content
      was efficient showing 93% lipid recovery with 8h drying and a power consumption
      of 0.017kWh. Scenedesmus biomass was also found to be rich in saturated and mono
      unsaturated fatty acids. Thus, the drying protocol demonstrates its suitability
      to improve the downstream processing of biodiesel production by significantly
      lowering the power consumption and the drying time. 

PMID- 25603531
TI  - Immunogenicity and anti-fecundity effect of nanoparticle coated glutathione S
      transferase (SjGST) DNA vaccine against murine Schistosoma japonicum infection.
AB  - There is still urgent need for a vaccine against schistosomiasis, especially in
      Schistosoma japonicum endemic areas where even a vaccine that will interrupt
      zoonotic transmission will be potentially effective as an intervention tool. We
      had developed a novel nanoparticle gene delivery system, which has proven
      efficacious in gene transfection to target immune cells with complementary
      adjuvant effect and high protective efficacy in several diseases. Here, we
      applied this nanoparticle system in combination with S. japonicum glutathione S
      transferase (SjGST) DNA vaccine to show the immunogenicity and anti-fecundity
      effect of the nanoparticle coated vaccine formulation against murine
      schistosomiasis. The nanoparticle-coated DNA vaccine formulation induced desired
      immune responses. In comparison with the nanoparticle coated empty vector, it
      produced significantly increased antigen-specific humoral response, T-helper 1
      polarized cytokine environment, higher proportion of IFN-gamma producing CD4(+) T
      cells and the concomitant decrease in IL-4 producing CD4(+) T-cells. Although
      there was no effect on worm burden, we recorded a marked reduction in tissue egg
      burden. There was up to 71.3% decrease in tissue egg burden and 55% reduction in
      the fecundity of female adult worms. Our data showed that SjGST DNA vaccine,
      delivered using the nanoparticle gene delivery system, produced anti-fecundity
      effect on female adult schistosomes as previously described by using conventional
      subunit vaccine with adjuvant, proving this DNA vaccine formulation as a
      promising candidate for anti-pathology and transmission blocking application. 

PMID- 25603532
TI  - SOHLH1 and SOHLH2 directly down-regulate STIMULATED BY RETINOIC ACID 8 (STRA8)
      expression.
AB  - As the name implies, Stimulated by Retinoic Acid 8 is an early retinoic acid (RA)
      responsive gene pivotal for the beginning of meiosis in female and male germ
      cells. Its expression is strictly time-dependent and cell-specific (pre-meiotic
      germ cells) and likely requires a complex mechanism of regulation. In this study,
      we demonstrate a direct negative control of SOHLH1 and SOHLH2, 2 germ cell
      specific bHLH transcription factors, on Stra8 expression. We observed a negative
      correlation between STRA8 and SOHLH1 expression in prepuberal differentiating
      mouse KIT(+) spermatogonia and found that SOHLH1 and SOHLH2 were able to directly
      and cooperatively repress STRA8 expression in cell lines in vitro through binding
      to its promoter. We also identified 2 canonical E-Box motives in the Stra8
      promoter that mediated the negative regulation of SOHLH1 and SOHLH2 on these gene
      both in the cell lines and KIT(+) spermatogonia. We hypothesize that this novel
      negative activity of SOHLH1 and SOHLH2 in male cooperates with that of other
      transcription factors to coordinate spermatogonia differentiation and the RA
      induced meiosis and in female ensures STRA8 down-regulation at mid-end stages of
      meiotic prophase I.

PMID- 25603533
TI  - Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in
      Sphere-Templated Hydrogels.
AB  - Rapid and controlled vascularization within biomaterials is essential for many
      applications in regenerative medicine. The extent of vascularization is
      influenced by a number of factors, including scaffold architecture. While
      properties such as pore size and total porosity have been studied extensively,
      the importance of controlling the interconnectivity of pores has received less
      attention. A sintering method was used to generate hydrogel scaffolds with
      controlled pore interconnectivity. Poly(methyl methacrylate) microspheres were
      used as a sacrificial agent to generate porous poly(ethylene glycol) diacrylate
      hydrogels with interconnectivity varying based on microsphere sintering
      conditions. Interconnectivity levels increased with sintering time and
      temperature with resultant hydrogel structure showing agreement with template
      structure. Porous hydrogels with a narrow pore size distribution (130-150 MUm)
      and varying interconnectivity were investigated for their ability to influence
      vascularization in response to gradients of platelet-derived growth factor-BB
      (PDGF-BB). A rodent subcutaneous model was used to evaluate vascularized tissue
      formation in the hydrogels in vivo. Vascularized tissue invasion varied with
      interconnectivity. At week 3, higher interconnectivity hydrogels had completely
      vascularized with twice as much invasion. Interconnectivity also influenced PDGF
      BB transport within the scaffolds. An agent-based model was used to explore the
      relative roles of steric and transport effects on the observed results. In
      conclusion, a technique for the preparation of hydrogels with controlled pore
      interconnectivity has been developed and evaluated. This method has been used to
      show that pore interconnectivity can independently influence vascularization of
      biomaterials. 

PMID- 25603535
TI  - Solitary Mastocytoma of the Eyelid in an Adult Patient With Prolidase Deficiency.
AB  - Prolidase deficiency and solitary mastocytoma of the eyelid are both exceedingly
      rare. Prolidase deficiency is an inherited connective tissue disorder that has
      systemic sequelae, such as intractable skin ulceration, poor wound healing,
      recurrent infections, and intellectual impairment. Cutaneous mastocytoma is an
      isolated, aberrant cutaneous aggregation of mast cells. A case of an adult with
      severe prolidase deficiency who developed cutaneous mastocytoma of the eyelid was
      presented. To the authors' knowledge, adult-onset solitary mastocytoma of the
      eyelid has never been reported previously.

PMID- 25603534
TI  - Pleomorphic Adenoma With Prominent Clear Cell Myoepithelioma Component of the
      Lacrimal Gland.
AB  - A case of a pleomorphic adenoma of the lacrimal gland with a prominent clear cell
      myoepitheliomatous component was reported. An 81-year-old Caucasian woman
      experienced a 2-month history of right supraorbital swelling and proptosis.
      Excisional biopsy revealed a multicomponent lesion including a stromal component
      featuring glandular structures made of small epithelioid and spindle cells and a
      trabecular component with small islands of vacuolated cells, displaced nuclei,
      and clear cytoplasm. Immunohistochemical analysis revealed strong cytokeratin
      AE1/3 reactivity and focal smooth muscle actin positivity. The pathologic
      findings including immunohistochemistry results were consistent with a
      pleomorphic adenoma with prominent clear cell myoepithelioma component. 

PMID- 25603536
TI  - YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5.
AB  - Programmed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis,
      but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We
      identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in
      a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1
      associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting
      the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down
      of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA.
      Upon genotoxic stress response, YAF2 promotes TP53 activation via association
      with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of
      PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the
      ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently
      overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally,
      impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration
      of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting
      defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade
      linking YAF2, PDCD5, and TP53 during genotoxic stress responses.

PMID- 25603537
TI  - Mitophagy in yeast: Molecular mechanisms and physiological role.
AB  - Mitochondria autophagy (mitophagy) is a process that selectively degrades
      mitochondria via autophagy. Recently, there has been significant progress in the
      understanding of mitophagy in yeast. Atg32, a mitochondrial outer membrane
      receptor, is indispensable for mitophagy. Phosphorylation of Atg32 is an initial
      cue for selective mitochondrial degradation. Atg32 expression and phosphorylation
      regulate the induction and efficiency of mitophagy. In addition to Atg32-related
      processes, recent studies have revealed that mitochondrial fission and the
      mitochondria-endoplasmic reticulum (ER) contact site may play important roles in
      mitophagy. Mitochondrial fission is required to regulate mitochondrial size.
      Mitochondria-ER contact is mediated by the ER-mitochondria encounter structure
      and is important to supply lipids from the ER for autophagosome biogenesis for
      mitophagy. Mitophagy is physiologically important for regulating the number of
      mitochondria, diminishing mitochondrial production of reactive oxygen species,
      and extending chronological lifespan under caloric restriction. These findings
      suggest that mitophagy contributes to maintain mitochondrial homeostasis.
      However, whether mitophagy selectively degrades damaged or dysfunctional
      mitochondria in yeast is unknown.

PMID- 25603538
TI  - Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3
      channels in glucagon secretion.
AB  - Peptide-hormone secretion is partially triggered by Ca2+ influx through voltage
      gated Ca2+ channels (VGCCs) and gene inactivation of Zn2+-sensitive Cav2.3-type
      VGCCs is associated with disturbed glucose homeostasis in mice. Zn2+ has been
      implicated in pancreatic islet cell crosstalk and recent findings indicate that
      sudden cessation of Zn2+ supply during hypoglycemia triggers glucagon secretion
      in rodents. Here we show that diethyldithiocarbamate (DEDTC), a chelating agent
      for Zn2+ and other group IIB metal ions, differentially affects blood glucose and
      serum peptide hormone level in wild-type mice and mice lacking the Cav2.3
      subunit. Fasting glucose and glucagon level were significantly higher in Cav2.3
      deficient compared to wild-type mice, while DEDTC Zn2+-chelation produced a
      significant and correlated increase of blood glucose and serum glucagon
      concentration in wild-type but not Cav2.3-deficient mice. Glucose tolerance tests
      revealed severe glucose intolerance in Zn2+-depleted Cav2.3-deficient but not
      vehicle-treated Cav2.3-deficient or Zn2+-depleted wildtype mice. Collectively,
      these findings indicate that Cav2.3 channels are critically involved in the Zn2+
      mediated suppression of glucagon secretion during hyperglycemia. Especially under
      conditions of Zn2+ deficiency, ablation or dysfunction of Cav2.3 channels may
      lead to severe disturbances in glucose homeostasis.

PMID- 25603539
TI  - Six-month functional recovery of stroke patients: a multi-time-point study.
AB  - The aim of this study is to compare the time-course changes in neurologic
      impairments (trunk control, motor function, sensory, and cognition) and recovery
      in functional impairments (activity of daily livings and gait) simultaneously
      from initiating rehabilitation to 6 months after stroke. Consecutive stroke
      patients were recruited from the department of nervous surgery, and transferred
      into the department of rehabilitation medicine and continued on treatment during
      the acute stage. Outcome measures were examined at the initial rehabilitation
      baseline, 1, 2, and 4 weeks after rehabilitation treatment, and 3, 4, 5, and 6
      months after stroke. Patients were assessed using the Trunk Impairment Scale, the
      Fugl-Meyer Motor and Sensory Assessments for the upper and lower limbs, Mini
      Mental State Examination, Functional Ambulation Category, and Modified Barthel
      Index. Twenty consecutive patients were analyzed in the study with complete
      assessments. The recovery was relatively rapid during the 4 weeks after treatment
      (P value ranges from <0.001 to <0.007) and then to a lesser extent decelerated
      between 3 and 6 months after stroke (P value between <0.001 and 0.080).
      Statistical comparison by repeated measures analysis showed a significant
      interaction between time points and measures of all recovery variables (P<0.001).
      Significant differences in level of impairments and functional recovery were
      found at the different time points. In comparison with the lower leg and trunk
      control, the upper arm showed less recovery, with a significant difference. All
      variables except for leg motor function improved continuously over 6 months after
      stroke. Nevertheless, this study confirms the importance of the period within 3
      months for recovery after stroke, during which most of the recovery occurred,
      ranging from 48 to 91%. Therefore, intensive treatment targeting motor and
      sensory functions early after stroke may be beneficial for recovery of
      impairments and functional performance. 

PMID- 25603540
TI  - Balance self-efficacy in older adults following inpatient rehabilitation.
AB  - Older adults discharging from inpatient rehabilitation were investigated to
      determine change in self-efficacy at 1 month after discharge, the relationship
      with discharge balance performance and physical function, and the influence of
      diagnosis. A prospective cohort of 101 adults older than 50 years of age, 43%
      men, average age 75.84 (SD 9.8) years, were recruited at discharge from inpatient
      rehabilitation. Balance self-efficacy was assessed using Activities-specific
      Balance Confidence (ABC) scale at discharge and 1 month following discharge.
      Balance and physical function were measured at discharge using the Functional
      Independence Measure, Balance Outcome Measure for Elder Rehabilitation, Modified
      Elderly Mobility Scale and gait speed. At discharge, balance self-efficacy was
      moderate (ABC score 62, SD 23) and did not change at follow-up. When grouped by
      discharge self-efficacy (ABC scores: low<50; moderate 51-80; high>80),
      significant between-group differences were found for balance (P=0.005) and
      physical function (P=0.035). At the 1-month follow-up, those with low discharge
      balance self-efficacy showed improvement (mean-change ABC score 12, 95%
      confidence interval 2-22) and those with high discharge balance self-efficacy had
      lower scores (mean-change ABC score 18, 95% confidence interval -8 to -28).
      Differences in ABC change scores were also found between diagnostic groups
      (F=3.740, P=0.03), with the orthopaedic group improving (ABC mean change=8) and
      the general frailty group showing a decrease in confidence (ABC mean change=10).
      The differences in balance self-efficacy change at 1 month following discharge
      were related to self-efficacy level at discharge and clinical group requiring
      rehabilitation. Clinicians need to be aware of these changes as patients are
      prepared for discharge. 

PMID- 25603541
TI  - Validity and reliability of the Serbian version of Patient-Reported Impact of
      Spasticity Measure in multiple sclerosis.
AB  - The Patient-Reported Impact of Spasticity Measure (PRISM) has been developed
      recently to assess the impact of spasticity on quality of life after spinal cord
      injury. Although PRISM may also be useful in patients with multiple sclerosis
      (MS), its psychometric properties in MS have not been established and PRISM is
      currently available only in English. The aims of this cross-sectional study were
      to translate PRISM into the Serbian language (PRISMSR) and examine its validity
      (construct, convergent, divergent) and reliability (internal consistency, test
      retest reliability) in 48 patients with spasticity because of MS diagnosed at
      least 1 year earlier and in remission at least 3 months. PRISMSR was administered
      twice 3 days apart. The validity of seven PRISMSR subscales was examined against
      the Modified Ashworth Scale (MAS), the Numerical Rating Scale (NRS) for
      spasticity, sex, and education. Internal consistency was assessed with Cronbach
      alpha and test-retest reliability with intraclass correlation coefficient for
      agreement (ICC2,1). During the forward-backward translation, only one PRISM item
      required minor cultural adaption. Almost all PRISMSR scores correlated
      significantly with MAS and NRS scores (r=0.29-0.51, 0.001<=P<=0.043). They were
      all significantly higher for MAS>=2 group versus the MAS<2 group
      (0.003<=P<=0.035) and for the NRS>=7 group versus the NRS<7 group
      (0.001<=P<=0.042), except for the Social Embarrassment subscale (P=0.083). The
      PRISMSR scores were not significantly different between sexes (P>=0.104) or those
      with high school versus college degree (P>=0.139). Both Cronbach alpha (0.78
      0.93) and test-retest ICC2,1 (0.82-0.90) were high. The original PRISM may be
      translated successfully into other languages. PRISMSR shows adequate validity and
      reliability for assessing the impact of spasticity on quality of life in patients
      with MS. 

PMID- 25603543
TI  - Activation of muscarinic receptors in rat parotid acinar cells induces AQP5
      trafficking to nuclei and apical plasma membrane.
AB  - BACKGROUND: The subcellular distribution of aquaporin-5 (AQP5) in rat parotid
      acinar cells in response to muscarinic acetylcholine receptor (mAChR) activation
      remains unclear. METHODS: Immunoconfocal and immunoelectron microscopy were used
      to visualize the distribution of AQP5 in parotid acinar cells. Western blotting
      was used to analyze AQP5 levels in membranes. To clarify the characteristics of
      membrane domains associated with AQP5, detergent solubility and sucrose-density
      flotation experiments were performed. RESULTS: Under control conditions, AQP5 was
      diffusely distributed on the apical plasma membrane (APM) and apical plasmalemmal
      region and throughout the cytoplasm. Upon mAChR activation, AQP5 was
      predominantly located in the nucleus, APM and lateral plasma membrane (LPM).
      Subsequently, localization of AQP5 in the nucleus, APM and LPM was decreased.
      Prolonged atropine treatment inhibited mAChR agonist-induced translocation of
      AQP5 to the nucleus, APM and LPM. AQP5 levels were enhanced in isolated nuclei
      and nuclear membranes prepared from parotid tissues incubated with mAChR agonist.
      mAChR agonist induced AQP5 levels in both soluble and insoluble nuclear fractions
      solubilized with Triton X-100 or Lubrol WX. Small amounts of AQP5 in nuclei were
      detected using low-density sucrose gradient. When AQP5 was present in the nuclear
      membrane, nuclear size decreased. CONCLUSION: The activation of mAChR induced
      AQP5 translocation to the nucleus, APM and LPM, and AQP5 may trigger water
      transport across the nuclear membrane and plasma membrane in rat parotid acinar
      cells. GENERAL SIGNIFICANCE: AQP5 translocates to the nuclear membrane and may
      trigger the movement of water, inducing shrinkage of the nucleus and the start of
      nuclear functions.

PMID- 25603544
TI  - Sunlight activated long-lasting luminescence from Ba5Si8O21: Eu(2+),Dy(3+)
      phosphor.
AB  - Visible-light persistent phosphors are commonly used as self-sustained night
      vision and fluorescence labeling materials. From the inspiration of the structure
      of six-membered rings plane in Ba4(Si3O8)2, a similar structure of Ba5Si8O21 is
      expected that could exhibit more excellent phosphorescence property. In this
      Article, we report a novel visible long-lasting luminescence phosphor of
      Eu(2+)/Dy(3+) codoped Ba5Si8O21 for the first time. Ba5Si8O21:Eu(2+),Dy(3+)
      phosphor could be activated effectively by sunlight or even in severe weather
      conditions, which is mainly attributed to the broad excitation spectrum (200-455
      nm) and highly responds to UV-A and violet-light in the solar spectrum. After
      activation, Ba5Si8O21:Eu(2+),Dy(3+) emits intense emission at 380-680 nm with
      persistent phosphorescence beyond 16 h. Moreover, it exhibits excellent and
      stable phosphorescence even in water, indicating that Ba5Si8O21:Eu(2+),Dy(3+)
      will be a all-weather material that can be effectively and repeatedly charged by
      natural daylight in all kinds of open-air environments. Furthermore, the quantum
      tunneling behavior was illustrated in the afterglow mechanism. 

PMID- 25603542
TI  - Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug,
      indomethacin induced inflammatory damage and apoptosis by modulating NF-kappaB
      pathway.
AB  - BACKGROUND: Deregulation in prostaglandin (PG) biosynthesis, severe oxidative
      stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal
      anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the
      prescribed anti-ulcer drugs generate various side effects. In this scenario, we
      could consider morin as a safe herbal potential agent against IND-gastropathy and
      rationalize its action systematically. METHODS: Rats were pretreated with morin
      for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti
      ulcerogenic nature of morin was assessed by morphological and histological
      analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules),
      ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-kappaB and apoptotic
      signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and
      ELISA at the time points of their maximal changes due to IND administration.
      RESULTS: IND induced NF-kappaB and apoptotic signaling in rat's gastric mucosa.
      These increased proinflammatory responses, but reduced the antioxidant enzymes
      and other protective factors. Morin reversed all the adverse effects to prevent
      IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not
      affect the absorption and/or primary pharmacological activity of IND.
      CONCLUSIONS: The gastroprotective action of morin is primarily attributed to its
      potent antioxidant nature that also helps in controlling several IND-induced
      inflammatory responses. GENERAL SIGNIFICANCE: For the first time, the study
      reveals a mechanistic basis of morin mediated protective action against IND
      induced gastropathy. As morin is a naturally abundant safe antioxidant, future
      detailed pharmacokinetic and pharmacodynamic studies are expected to establish it
      as a gastroprotective agent.

PMID- 25603545
TI  - Rituximab for rheumatoid arthritis.
AB  - BACKGROUND: Rituximab is a selective, B-cell depleting, biologic agent for
      treating refractory rheumatoid arthritis (RA). It is a chimeric monoclonal
      antibody targeted against CD 20 that is promoted as therapy for patients who fail
      to respond to other biologics. There is evidence to suggest that rituximab is
      effective and well tolerated when used in combination with methotrexate for RA.
      OBJECTIVES: To evaluate the benefits and harms of rituximab for the treatment of
      RA. SEARCH METHODS: We conducted a search (until January 2014) in electronic
      databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science),
      clinical trials registries, and websites of regulatory agencies. Reference lists
      from comprehensive reviews were also screened. SELECTION CRITERIA: All controlled
      trials comparing treatment with rituximab as monotherapy or in combination with
      any disease modifying anti-rheumatic drug (DMARD) (traditional or biologic)
      versus placebo or other DMARD (traditional or biologic) in adult patients with
      active RA. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the risk of bias and abstracted data from each study. MAIN RESULTS: We
      included eight studies with 2720 patients. For six studies selection bias could
      not be evaluated and two studies were considered to have low risk of bias. The
      level of evidence ranged from low to high, but was rated as moderate for most
      outcomes. We have prioritised reporting of rituximab (two 1000 mg doses) in
      combination with methotrexate since this is the approved dose and most commonly
      used combination. We also reported data on other combinations and doses as
      supplementary information in the results section of the review.American College
      of Rheumatology (ACR) 50 response rates were statistically significantly improved
      with rituximab (two 1000 mg doses) in combination with methotrexate compared with
      methotrexate alone at 24 to 104 weeks. The RR for achieving an ACR 50 at 24 weeks
      was 3.3 (95% CI 2.3 to 4.6); 29% of patients receiving rituximab (two 1000 mg
      doses) in combination with methotrexate achieved the ACR 50 compared to 9% of
      controls. The absolute treatment benefit (ATB) was 21% (95% CI 16% to 25%) with a
      number needed to treat (NNT) of 6 (95% CI 4 to 9).At 52 weeks, the RR for
      achieving clinical remission (Disease Activity Score (DAS) 28 joints < 2.6) with
      rituximab (two 1000 mg doses) in combination with methotrexate compared with
      methotrexate monotherapy was 2.4 (95% CI 1.7 to 3.5); 22% of patients receiving
      rituximab (two 1000 mg doses) in combination with methotrexate achieved clinical
      remission compared to 11% of controls. The ATB was 11% (95% CI 2% to 20%) with a
      NNT of 7 (95% CI 4 to 13).At 24 weeks, the RR for achieving a clinically
      meaningful improvement (CMI) in the Health Assessment Questionnaire (HAQ) (>
      0.22) for patients receiving rituximab combined with methotrexate compared to
      patients on methotrexate alone was 1.6 (95% CI 1.2 to 2.1). The ATB was 24% (95%
      CI 12% to 36%) with an NNT of 5 (95% CI 3 to 13). At 104 weeks, the RR for
      achieving a CMI in HAQ (> 0.22) was 1.4 (95% CI 1.3 to 1.6). The ATB was 24% (95%
      CI 16% to 31%) with a NNT of 5 (95% CI 3 to 7).At 24 weeks, the RR for preventing
      radiographic progression in patients receiving rituximab (two 1000 mg doses) in
      combination with methotrexate was 1.2 (95% CI 1.0 to 1.4) compared to
      methotrexate alone; 70% of patients receiving rituximab (two 1000 mg doses) in
      combination with methotrexate had no radiographic progression compared to 59% of
      controls. The ATB was 11% (95% CI 2% to 19%) and the NNT was 10 (95% CI 5 to 57).
      Similar benefits were observed at 52 to 56 weeks and 104 weeks.Statistically
      significantly more patients achieved a CMI on the physical and mental components
      of the quality of life, measured by the Short Form (SF)-36, in the rituximab (two
      1000 mg doses) in combination with methotrexate-treated group compared with
      methotrexate alone at 24 to 52 weeks (RR 2.0, 95% CI 1.1 to 3.4; NNT 4, 95% CI 3
      to 8 and RR 1.4, 95% CI 1.1 to 1.9; NNT 8, 95% CI 5 to 19, respectively); 34 and
      13 more patients out of 100 showed an improvement in the physical component of
      the quality of life measure compared to methotrexate alone (95% CI 5% to 84%; 95%
      CI 7% to 8%, respectively).There was no evidence of a statistically significant
      difference in the rates of withdrawals because of adverse events or for other
      reasons (that is, withdrawal of consent, violation, administrative, failure to
      return) in either group. However, statistically significantly more people
      receiving the control drug withdrew from the study compared to those receiving
      rituximab (two 1000 mg doses) in combination with methotrexate at all times (RR
      0.40, 95% CI 0.32 to 0.50; RR 0.61, 95% CI 0.40 to 0.91; RR 0.48, 95% CI 0.28 to
      0.82; RR 0.58, 95% CI 0.45 to 0.75, respectively). At 104 weeks, 37% withdrew
      from the control group and 20% withdrew from the rituximab (two 1000 mg doses) in
      combination with methotrexate group. The absolute risk difference (ARD) was -20%
      (95% CI -34% to -5%) with a number needed to harm (NNH) of 7 (95% CI 5 to 11).A
      greater proportion of patients receiving rituximab (two 1000 mg doses) in
      combination with methotrexate developed adverse events after their first infusion
      compared to those receiving methotrexate monotherapy and placebo infusions (RR
      1.6, 95% CI 1.3 to 1.9); 26% of those taking rituximab plus methotrexate reported
      more events associated with their first infusion compared to 16% of those on the
      control regimen with an ARD of 9% (95% CI 5% to 13%) and a NNH of 11 (95% CI 21
      to 8). However, no statistically significant differences were noted in the rates
      of serious adverse events. AUTHORS' CONCLUSIONS: Evidence from eight studies
      suggests that rituximab (two 1000 mg doses) in combination with methotrexate is
      significantly more efficacious than methotrexate alone for improving the symptoms
      of RA and preventing disease progression.

PMID- 25603546
TI  - Exercise for treating patellofemoral pain syndrome.
AB  - BACKGROUND: Patellofemoral pain syndrome (PFPS) is a common knee problem, which
      particularly affects adolescents and young adults. PFPS, which is characterised
      by retropatellar (behind the kneecap) or peripatellar (around the kneecap) pain,
      is often referred to as anterior knee pain. The pain mostly occurs when load is
      put on the knee extensor mechanism when climbing stairs, squatting, running,
      cycling or sitting with flexed knees. Exercise therapy is often prescribed for
      this condition. OBJECTIVES: To assess the effects (benefits and harms) of
      exercise therapy aimed at reducing knee pain and improving knee function for
      people with patellofemoral pain syndrome. SEARCH METHODS: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (May 2014), the
      Cochrane Central Register of Controlled Trials (2014, Issue 4), MEDLINE (1946 to
      May 2014), EMBASE (1980 to 2014 Week 20), PEDro (to June 2014), CINAHL (1982 to
      May 2014) and AMED (1985 to May 2014), trial registers (to June 2014) and
      conference abstracts. SELECTION CRITERIA: Randomised and quasi-randomised trials
      evaluating the effect of exercise therapy on pain, function and recovery in
      adolescents and adults with patellofemoral pain syndrome. We included comparisons
      of exercise therapy versus control (e.g. no treatment) or versus another non
      surgical therapy; or of different exercises or exercise programmes. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials based
      on pre-defined inclusion criteria, extracted data and assessed risk of bias.
      Where appropriate, we pooled data using either fixed-effect or random-effects
      methods. We selected the following seven outcomes for summarising the available
      evidence: pain during activity (short-term: <= 3 months); usual pain (short
      term); pain during activity (long-term: > 3 months); usual pain (long-term);
      functional ability (short-term); functional ability (long-term); and recovery
      (long-term). MAIN RESULTS: In total, 31 heterogeneous trials including 1690
      participants with patellofemoral pain are included in this review. There was
      considerable between-study variation in patient characteristics (e.g. activity
      level) and diagnostic criteria for study inclusion (e.g. minimum duration of
      symptoms) and exercise therapy. Eight trials, six of which were quasi-randomised,
      were at high risk of selection bias. We assessed most trials as being at high
      risk of performance bias and detection bias, which resulted from lack of
      blinding.The included studies, some of which contributed to more than one
      comparison, provided evidence for the following comparisons: exercise therapy
      versus control (10 trials); exercise therapy versus other conservative
      interventions (e.g. taping; eight trials evaluating different interventions); and
      different exercises or exercise programmes. The latter group comprised:
      supervised versus home exercises (two trials); closed kinetic chain (KC) versus
      open KC exercises (four trials); variants of closed KC exercises (two trials
      making different comparisons); other comparisons of other types of KC or
      miscellaneous exercises (five trials evaluating different interventions); hip and
      knee versus knee exercises (seven trials); hip versus knee exercises (two
      studies); and high- versus low-intensity exercises (one study). There were no
      trials testing exercise medium (land versus water) or duration of exercises.
      Where available, the evidence for each of seven main outcomes for all comparisons
      was of very low quality, generally due to serious flaws in design and small
      numbers of participants. This means that we are very unsure about the estimates.
      The evidence for the two largest comparisons is summarised here. Exercise versus
      control. Pooled data from five studies (375 participants) for pain during
      activity (short-term) favoured exercise therapy: mean difference (MD) -1.46, 95%
      confidence interval (CI) -2.39 to -0.54. The CI included the minimal clinically
      important difference (MCID) of 1.3 (scale 0 to 10), indicating the possibility of
      a clinically important reduction in pain. The same finding applied for usual pain
      (short-term; two studies, 41 participants), pain during activity (long-term; two
      studies, 180 participants) and usual pain (long-term; one study, 94
      participants). Pooled data from seven studies (483 participants) for functional
      ability (short-term) also favoured exercise therapy; standardised mean difference
      (SMD) 1.10, 95% CI 0.58 to 1.63. Re-expressed in terms of the Anterior Knee Pain
      Score (AKPS; 0 to 100), this result (estimated MD 12.21 higher, 95% CI 6.44 to
      18.09 higher) included the MCID of 10.0, indicating the possibility of a
      clinically important improvement in function. The same finding applied for
      functional ability (long-term; three studies, 274 participants). Pooled data (two
      studies, 166 participants) indicated that, based on the 'recovery' of 250 per
      1000 in the control group, 88 more (95% CI 2 fewer to 210 more) participants per
      1000 recovered in the long term (12 months) as a result of exercise therapy. Hip
      plus knee versus knee exercises. Pooled data from three studies (104
      participants) for pain during activity (short-term) favoured hip and knee
      exercise: MD -2.20, 95% CI -3.80 to -0.60; the CI included a clinically important
      effect. The same applied for usual pain (short-term; two studies, 46
      participants). One study (49 participants) found a clinically important reduction
      in pain during activity (long-term) for hip and knee exercise. Although tending
      to favour hip and knee exercises, the evidence for functional ability (short
      term; four studies, 174 participants; and long-term; two studies, 78
      participants) and recovery (one study, 29 participants) did not show that either
      approach was superior. AUTHORS' CONCLUSIONS: This review has found very low
      quality but consistent evidence that exercise therapy for PFPS may result in
      clinically important reduction in pain and improvement in functional ability, as
      well as enhancing long-term recovery. However, there is insufficient evidence to
      determine the best form of exercise therapy and it is unknown whether this result
      would apply to all people with PFPS. There is some very low quality evidence that
      hip plus knee exercises may be more effective in reducing pain than knee exercise
      alone.Further randomised trials are warranted but in order to optimise research
      effort and engender the large multicentre randomised trials that are required to
      inform practice, these should be preceded by research that aims to identify
      priority questions and attain agreement and, where practical, standardisation
      regarding diagnostic criteria and measurement of outcome.

PMID- 25603547
TI  - Multi-level hot zone identification for pedestrian safety.
AB  - According to the National Highway Traffic Safety Administration (NHTSA), while
      fatalities from traffic crashes have decreased, the proportion of pedestrian
      fatalities has steadily increased from 11% to 14% over the past decade. This
      study aims at identifying two zonal levels factors. The first is to identify hot
      zones at which pedestrian crashes occurs, while the second are zones where crash
      involved pedestrians came from. Bayesian Poisson lognormal simultaneous equation
      spatial error model (BPLSESEM) was estimated and revealed significant factors for
      the two target variables. Then, PSIs (potential for safety improvements) were
      computed using the model. Subsequently, a novel hot zone identification method
      was suggested to combine both hot zones from where vulnerable pedestrians
      originated with hot zones where many pedestrian crashes occur. For the former
      zones, targeted safety education and awareness campaigns can be provided as
      countermeasures whereas area-wide engineering treatments and enforcement may be
      effective safety treatments for the latter ones. Thus, it is expected that
      practitioners are able to suggest appropriate safety treatments for pedestrian
      crashes using the method and results from this study. 

PMID- 25603548
TI  - On-road experiment to assess drivers' detection of roadside targets as a function
      of headlight system, target placement, and target reflectance.
AB  - Adaptive headlights swivel with steering input to keep the beams on the roadway
      as drivers negotiate curves. To assess the effects of this feature on driver's
      visual performance, a field experiment was conducted at night on a rural, unlit,
      and unlined two-lane road during which 20 adult participant drivers searched a
      set of 60 targets. High- (n=30) and low- (n=30) reflectance targets were evenly
      distributed on straight road sections and on the inside or outside of curves.
      Participants completed three target detection trials: once with adaptive high
      intensity discharge (HID) headlights, once with fixed HID headlights, and once
      with fixed halogen headlights. Results indicated the adaptive HID headlights
      helped drivers detect targets that were most difficult to see (low reflectance)
      at the points in curves found by other researchers to be most crucial for
      successful navigation (inside apex). For targets placed on straight stretches of
      road or on the outside of curves, the adaptive feature provided no significant
      improvement in target detection. However, the pattern of results indicate that
      HID lamps whether fixed or adaptive improved target detection somewhat,
      suggesting that part of the real world crash reduction measured for this adaptive
      system (Highway Loss Data Institute (HLDI), 2012a) may be due to the differences
      in the light source (HID vs. halogen). Depending on the scenario, the estimated
      benefits to driver response time associated with the tested adaptive (swiveling
      HID) headlights ranged from 200 to 380ms compared with the fixed headlight
      systems tested. 

PMID- 25603549
TI  - The new wave of clinical wavefronts.

PMID- 25603550
TI  - Wavefront refraction and correction.

PMID- 25603555
TI  - Polymorphisms in VDR gene in Tunisian postmenopausal women are associated with
      osteopenia phenotype.
AB  - OBJECTIVES: Osteopenia is characterized by intermediate values of bone mineral
      density (BMD) as compared to normal and osteoporotic subjects. BMD, a surrogate
      phenotype for osteoporosis, is influenced in part by genetic factors. Among the
      genes associated with BMD, the vitamin D receptor (VDR) was the first gene
      studied as a potential candidate associated with BMD in adult and postmenopausal
      bone loss. However, results are controversial. METHODS: To determine whether VDR
      polymorphisms ApaI and TaqI are associated with BMD, osteopenia, osteoporosis and
      low-impact fracture risk in North Africans, these genotypes were analyzed in 566
      postmenopausal Tunisian women. RESULTS: In postmenopausal Tunisian women, the GT
      ApaI genotype seems to be protective against osteoporosis development (p = 0.02;
      odds ratio = 0.54). Moreover, the presence of the combined GT/TT genotype of ApaI
      and TaqI polymorphisms is more frequent in normal BMD women than in osteoporotic
      women (p = 0.00; odds ratio = 0.41). Interestingly, the GG ApaI genotype is
      associated with osteopenia development (p = 0.02; odds ratio = 1.86) and also the
      TT TaqI polymorphism (p = 0.02; odds ratio = 1.53). The GG ApaI genotype is
      associated with a three times risk of vertebral fracture. CONCLUSIONS: The ApaI
      polymorphism showed an association with osteopenia and low-impact vertebral
      fracture incidence but not with osteoporosis. The TaqI polymorphism is associated
      specifically with the osteopenia phenotype. The presence of the two polymorphisms
      increases the risk to develop osteopenia in postmenopausal Tunisian women.
      Osteopenia seems to be genetically determined. However, osteoporosis is the
      result of interaction between genetic and environmental factors.

PMID- 25603556
TI  - Palmitate activation by fatty acid transport protein 4 as a model system for
      hepatocellular apoptosis and steatosis.
AB  - Fatty acid transport protein (FATP) 4 is a minor FATP in the liver but it has
      some activity towards palmitate 16:0 (Pal). We here chose FATP4 as a
      representative model enzyme for acyl-CoA synthetases (ACSs), and FATPs to
      determine whether Pal activation would lead to apoptosis and alteration in lipid
      metabolism. By using FATP4 overexpressed (FATP4) Huh-7 cells, we showed that
      FATP4 was localized in the endoplasmic reticulum (ER) and mitochondria of FATP4
      cells. FATP4 cells were more responsive to Pal than the control GFP cells in
      increasing palmitoyl-CoA and oleoyl-CoA activities as well as apoptosis by ~2-3
      folds. The lipoapoptosis susceptibility by FATP4 was coupled with the increased
      JNK, PUMA, caspase3, PARP-1 activation as well as Rac-1-mediated cytoskeletal
      reorganization, and decreased insulin sensitivity. This was associated with
      increased contents of neutral lipids and significant alteration in composition of
      phospholipids and sphingolipids including increased lysophosphatidylcholine
      (LPC), ceramide, and hexosylceramide, as well as an increase of
      saturated:polyunsaturated fatty acid ratio in LPC and PC, but a decrease of this
      ratio in phosphatidylethanolamine pool. By use of ceramide synthase inhibitors,
      our results showed that FATP4-sensitized lipoapoptosis was not mediated by
      ceramides. Moreover, FATP4 expression was increased in fatty livers in vivo.
      Thus, our model system has provided a clue that Pal activation FATP4 triggers
      hepatocellular apoptosis via altered phospholipid composition and steatosis by
      acylation into complex lipids. This may be a redundant mechanism for other ER
      localizing ACSs and FATPs in the liver, and hence their involvement in the
      development of fatty liver disease. 

PMID- 25603557
TI  - Unravelling plant molecular machineries through affinity purification coupled to
      mass spectrometry.
AB  - Rather than functioning independently, proteins tend to work in concert with each
      other and with other macromolecules to form macromolecular complexes. Affinity
      purification coupled to mass spectrometry (AP-MS) can lead to a better
      understanding of the cellular functions of these complexes. With the development
      of easy purification protocols and ultra-sensitive MS, AP-MS is currently widely
      used for screening co-complex membership in plants. Studying complexes in their
      developmental context through the isolation of specific organs and tissues has
      now become feasible. Besides, the tagged protein can be employed for probing
      other interactions like protein-DNA and protein-RNA interactions. With the tools
      at hand, protein-centred interaction studies will greatly improve our knowledge
      of how plant cells wire their functional components in relation to their
      function. 

PMID- 25603558
TI  - The effects of evolution education: examining attitudes toward and knowledge of
      evolution in college courses.
AB  - The present study examined changes in university students' attitudes toward and
      knowledge of evolution measured by the previously validated Evolutionary
      Attitudes and Literacy Survey (EALS) in response to curricular content.
      Specifically, student responses on the survey were compared across an
      evolutionary psychology course, an introductory biology course with significant
      evolutionary content, and a political science course with no evolutionary
      content. To this end, 868 students were assessed at a large Midwestern U.S.
      university prior to and following completion of one of the three courses. A
      multiple group repeated measures confirmatory factor analysis (CFA) was conducted
      to examine latent mean differences in self-reported Evolution
      Knowledge/Relevance, Creationist Reasoning, Evolutionary Misconceptions, and
      Exposure to Evolution. A significant and notable increase in Knowledge/Relevance,
      as well as decreases in Creationist Reasoning and Evolutionary Misconceptions,
      was observed for the evolutionary psychology course, whereas the biology course
      demonstrated no change in Knowledge/Relevance and a significant increase in
      Evolutionary Misconceptions. The implications of these findings for evolution
      education are discussed. 

PMID- 25603560
TI  - [End-to-side anastomosis of a bronchial branch to the bronchus].

PMID- 25603559
TI  - Facile Synthesis of Molecularly Imprinted Graphene Quantum Dots for the
      Determination of Dopamine with Affinity-Adjustable.
AB  - A facilely prepared fluorescence sensor was developed for dopamine (DA)
      determination based on polyindole/graphene quantum dots molecularly imprinted
      polymers (PIn/GQDs@MIPs). The proposed sensor exhibits a high sensitivity with a
      linear range of 5 * 10(-10) to 1.2 * 10(-6) M and the limit of detection as low
      as 1 * 10(-10) M in the determination of DA, which is probably due to the tailor
      made imprinted cavities for binding DA thought hydrogen bonds between amine
      groups of DA and oxygen-containing groups of the novel composite. Furthermore,
      the prepared sensor can rebind DA in dual-type: a low affinity type (noncovalent
      interaction is off) and a high affinity type (noncovalent interaction is on), and
      the rebinding interaction can be adjusted by tuning the pH, which shows a unique
      potential for adjusting the binding interaction while keeping the specificity,
      allowing for wider applications. 

PMID- 25603561
TI  - [Excision of the apex region of the right lung].

PMID- 25603562
TI  - [Questions and answers on imaging diagnosis. Multiple arterio-venous fistulas of
      both lungs].

PMID- 25603563
TI  - [E-cigarette stirs controversies].

PMID- 25603564
TI  - [Lungs et diving].
AB  - Whilst underwater, the body is submitted to significant variations of the
      surrounding pressure according to the depth. These conditions modify the
      hemodynamic and the ventilatory mechanics considerably. Some repercussions, like
      pulmonary barotrauma, are related to simple physical phenomena. Others, like
      decompression sickness, are due to more com- plex processes. Breath-hold diving
      disrupts haematosis and can be complicated by alveolar haemorrhage and loss of
      consciousness. Acute pulmonary oedema during scuba-diving, breath-hold diving and
      swimming has been reported more recently. In case of pulmonary disorders scuba
      diving is contraindicated most of the time. It is therefore highly recommended to
      seek medical advice to prevent problems.

PMID- 25603565
TI  - [Bronchial hyperresponsiveness and its importance for the clinician].
AB  - Asthma is a chronic inflammatory airway disease, characterised by bronchial
      hyperresponsiveness causing bronchoconstriction, and thereby provoking typical
      symptoms (dyspnoea, cough, wheezing). Bronchial hyperres- ponsiveness indicates a
      temporary airflow limitation when exposed to a bronchoconstricting stimulus. Its
      measurement by challenge tests can be a valuable tool for confirming or excluding
      asthma, as well as for evaluating the efficacy of treatment. However, the origin
      of bronchial hyperresponsiveness is multifactorial and the different challenge
      tests are not equivalent. Direct challenge tests, like methacholine, mainly
      reflect chronic airway remo- delling, whereas indirect tests, like mannitol,
      better reflect bronchial inflammation.

PMID- 25603566
TI  - [Assessment and management of chronic cough in adults].
AB  - Chronic cough is one of the most common symptoms for which outpatient care is
      sought. The most frequent causes are upper airway cough syndrome, asthma, and
      gastroesophageal reflux. It is often difficult to determine the origin of chronic
      cough based on the medical history and physical examination. Empirical treatment
      directed at the three aforementioned etiologies is thus of considerable value in
      the initial workup. Treatment failure is most commonly due to insufficient
      treatment (dosage or duration) or to the coexistence of several causes needing
      simultaneous use of different drugs.

PMID- 25603567
TI  - [Invasive pulmonary aspergillosis and chronic pulmonary aspergillosis].
AB  - Aspergillus pulmonary infection causes a spectrum of diverse diseases according
      to host immunity. The two major entities are invasive pulmonary aspergillosis and
      chronic pulmonary aspergillosis. The later can be divided into aspergilloma, then
      into chronic cavitary, more or less fibrosing aspergillosis, and finally into
      chronic necrotizing aspergillosis, or semiinvasive aspergillosis. The present
      article reviews this complex classification, which is necessary to reflect the
      diverse clinical aspect of the disease. Allergic broncho-pulmonary aspergillosis
      (ABPA), which is more a hypersensitivity reaction than an infectious process,
      will not be discussed here.

PMID- 25603569
TI  - [Residual excessive daytime sleepiness in CPAP-treated obstructive sleep apnea].
AB  - Obstructive sleep apnea (OSA) is a common condition most often characterized by
      daytime sleepiness. cPAP therapy is very effective in reversing symptoms.
      However, some patients still complain of excessive daytime sleepiness despite
      treatment, It is essential to document sufficient use of CPAP and to rule out the
      presence of residual respiratory events. Search for other underlying causes of
      sleepiness are then to be investigated by a detailed history together with a
      sleep night recording. The purpose of this article is to guide the clinician in
      providing comprehensive medical care for those patients.

PMID- 25603568
TI  - [Idiopathic pulmonary fibrosis: recent diagnostic and therapeutic advances].
AB  - Idiopathic pulmonary fibrosis (IPF) is the most frequent of the idiopathic
      interstitial pneumonias. It is a progressive disorderwith a poor prognosis. Its
      diagnosis requires the careful exclusion of potential causes, and a pattern of
      usual interstitial pneumonia at high-resolution computed tomography or video
      assisted surgical lung biopsy. Several recent randomized trials have profoundly
      modified the therapeutic management of IPF. The combination of prednisone and
      azathioprine, often prescribed until recently, has been shown to be harmful and
      is no longer indicated. N-acetylcystein, also used in the past decade, failed to
      show an efficacy. However, two new antifibrotic drugs, pirfenidone and
      nintedanib, have for the first time proven effective in slowing disease
      progression.

PMID- 25603570
TI  - [Managing diversity in Swiss Health care].
AB  - The development of Migrant Friendly Hospitals is an important first step towards
      eliminating health care disparities in Switzerland and an important reminder to
      health policy makers and practitioners across the health care system of their
      responsibility to provide non-discriminatory quality health care to all patients.

PMID- 25603572
TI  - [Nightmares].

PMID- 25603573
TI  - [Ebola: guide for burial and dignity].

PMID- 25603571
TI  - [Whenever possible, forbid 3D image viewing before age 6].

PMID- 25603574
TI  - [Patients with severe dementia living in nursing homes: too many medication for
      too long?].

PMID- 25603575
TI  - [Assisted suicide in houses for elderly: must it be legislated?].

PMID- 25603576
TI  - [Expensive medical equipments purchasing plan: an idea from Switzerland?].

PMID- 25603577
TI  - [Alcoholism: french anesthetists come clean].

PMID- 25603578
TI  - New social tasks for cognitive psychology; or, new cognitive tasks for social
      psychology.
AB  - To elucidate how differing theories of rationality lead to differing practices,
      their social rules must be analyzed. This is true not merely in science but also
      in society at large. This analysis of social thinking requires both the
      identification of innate cognitive social psychological processes and
      explanations of their relations with differing rules of rational practice. These
      new tasks can enable social psychologists to contribute to the study of how
      social situations facilitate or inhibit rational practice and enable cognitive
      psychologists to improve social psychological theory. In contrast to dominant
      current research strategies, social and cognitive psychologists can integrate
      social studies of rational practices and their consequences with studies of
      underlying cognitive psychological processes. In this article I do not attempt to
      carry out these tasks but rather point to both their lack of recognition and
      their importance.

PMID- 25603579
TI  - Socioeconomic status and adolescent aggression: the role of executive functioning
      as a mediator.
AB  - The primary focus of the present study was to determine the direct and indirect
      relations between socioeconomic status (SES), executive functioning (EF), and
      adolescent aggression. The test sample included 512 adolescents (girls = 255,
      boys = 257) of secondary and higher secondary grade within the age range of 13-19
      years. Participants completed measures of SES and aggression in group settings,
      followed by the individual administration of tests of EF. Findings provided
      support for the meditational effect of executive skills in the relation between
      SES and aggression. Specifically, results showed that SES is positively and
      directly related to EF and indirectly related to aggression through EF.
      Implications of the study along with limitations and suggestions for future
      research are discussed.

PMID- 25603580
TI  - Emotions in the classroom: the role of teachers' emotional intelligence ability
      in predicting students' achievement.
AB  - School days can be a difficult time, especially when students are faced with
      subjects that require motivational investment along with cognitive effort, such
      as mathematics and sciences. In the present study, we investigated the effects of
      teachers' emotional intelligence (El) ability, self-efficacy, and emotional
      states and students' self-esteem, perceptions of ability, and metacognitive
      beliefs in predicting school achievement. We hypothesized that the level of
      teacher EI ability would moderate the impact of students' self-perceptions and
      beliefs about their achievements in mathematics and sciences. Students from
      Italian junior high schools (N = 338) and their math teachers (N = 12) were
      involved in the study, and a multilevel approach was used. Findings showed that
      teachers' EI has a positive role in promoting students' achievement, by enhancing
      the effects of students' self-perceptions of ability and self-esteem.These
      results have implications for the implementation of intervention programs on the
      emotional, motivational, and metacognitive correlates of studying and learning
      behavior.

PMID- 25603581
TI  - Incremental validity of emotional intelligence ability in predicting academic
      achievement.
AB  - We tested the incremental validity of an ability measure of emotional
      intelligence (El) in predicting academic achievement in undergraduate students,
      controlling for cognitive abilities and personality traits. Academic achievement
      has been conceptualized in terms of the number of exams, grade point average, and
      study time taken to prepare for each exam. Additionally, gender differences were
      taken into account in these relationships. Participants filled in the Mayer
      Salovey-Caruso Emotional Intelligence Test (MSCEIT), the Raven's Advanced
      Progressive Matrices, the reduced version of the Eysenck Personality
      Questionnaire, and academic achievement measures. Results showed that El
      abilities were positively related to academic achievement indices, such as the
      number of exams and grade point average; total El ability and the Perceiving
      branch were negatively associated with the study time spent preparing for exams.
      Furthermore, El ability adds a percentage of incremental variance with respect to
      cognitive ability and personality variables in explaining scholastic success. The
      magnitude of the associations between El abilities and academic achievement
      measures was generally higher for men than for women. Jointly considered, the
      present findings support the incremental validity of the MSCEIT and provide
      positive indications of the importance of El in students' academic development.
      The helpfulness of El training in the context of academic institutions is
      discussed.

PMID- 25603582
TI  - Isomorphic categories.
AB  - Learning and transfer were investigated for a categorical structure that could be
      mapped without loss of information from 1 sensory modality to another. The
      category space was composed of 3 nonoverlapping, linearly separable categories
      whose members were structured, temporal events. Each stimulus was composed of a
      sequence of on-off events that varied in duration and number of subevents
      (complexity). Categories were learned visually, haptically, or auditorily and
      transferred to the same or another modality. Despite the.isomorphism across
      modalities, significant differences appeared in both learning and transfer. The
      visual modality showed an early learning advantage, with information on the
      transfer test preserved best when encoded visually during learning, worst when
      encoded haptically, with auditory encoding intermediate. False recognition rates
      were elevated when categories were learned haptically and transferred to another
      modality. In general, classification accuracy was highest for the category
      prototype, with false recognition of the category prototype higher in the cross
      modality conditions. The results are discussed in terms of current theories in
      modality transfer including the difficulties inherent when calculation of
      similarity must be considered in a cross-modal situation.

PMID- 25603583
TI  - IMM: a multisystem memory model for conceptual learning.
AB  - Concepts of learning and memory are closely related, and the terms often describe
      the same processes. Conceptual learning is known to be the process of developing
      abstract rules or mental constructs based on sensory experience. The Integrated
      Model of Mind (IMM), introduced in the present work, is a theoretical multisystem
      memory model that describes how concepts are formed. The IMM in its design
      arranges memory systems after their function in an integrated and harmonized
      sequence. It provides answers to some limitations of Tulving's serial-parallel
      independent (SPI) model and suggests a new assumption with respect to mental
      representation and image schema construction through the process of encoding.

PMID- 25603584
TI  - Comparison of interstimulus intervals on change detection in nondriving and
      driving scenarios.
AB  - Change detection across disruptions of visual scenes is typically studied using
      brief durations of the interstimulus interval (ISI) (i.e., up to 300 ms). We
      investigated change detection across durations that approximate longer, voluntary
      glances away from a visual scene (i.e., 500-2,000 ms), which are often actualized
      in driving situations. Experiment 1 found that in nondriving scenarios, change
      detection performance, as measured by accuracy and response time, decreased as
      ISI increased. Experiment 2 found that in driving scenarios, change detection for
      plausible changes also decreased as the ISI increased, but there was no similar
      decrease in performance for implausible changes. Both Experiments 1 and 2 showed
      that the necessary number of exposures to the change decreased as ISIs
      approximated voluntary glances, suggesting that change detection strategies may
      be modified at longer ISI durations.

PMID- 25603585
TI  - E. B. Titchener, women psychologists, and the experimentalists.
AB  - A well-known fact is that E. B. Titchener, a major figure in psychology in the
      first quarter of the 20th century, excluded women from the group known as the
      Experimentalists, which he formed in 1904. This fact provides the basis for
      depicting him as a misogynist. Less well known and publicized is that he was
      arguably the strongest advocate for women psychologists in the United States
      throughout his academic career. He supervised the graduate study of Margaret
      Washburn, the first woman to receive a PhD in psychology in the United States,
      directed more than 20 dissertations for women psychologists, most of which were
      published in The American Journal of Psychology, and influenced and befriended
      others who were not his PhD students. The purpose of this article is to make
      psychologists more aware of the prominent role Titchener played in the education
      of early women psychologists and to reconcile this contribution with his position
      that the Experimentalists should be restricted to men.

PMID- 25603586
TI  - A French description of the Psychology Laboratory of G. S. Hall at Clark
      University in 1893.
AB  - There is a rich tradition of writings about the foundation of psychology
      laboratories, particularly in the United States and in France. Like their German
      counterparts, American laboratories of psychology were described by several
      scholars in French journals. These descriptions stimulated the establishment of
      laboratories in France and provided templates for laboratory designs. We
      introduce here an article written by Marcel Baudouin (1860-1941), who visited and
      subsequently described the psychology laboratory of Granville Stanley Hall (1844
      1924) at Clark University in Worcester, Massachusetts. The English translation of
      Baudouin's paper, provided here, constitutes an interesting new document on
      Hall's laboratory at Clark University as it stood in 1893. From the French
      perspective, the Clark laboratory provided an ideal model for the experimental
      psychology laboratory.

PMID- 25603587
TI  - Obesity, metformin and prostate cancer risk.

PMID- 25603588
TI  - Patients with gout can be cured in primary care.
AB  - Gout affects 2.5% of the total UK population and is four times more common in men
      than women. The peak prevalence and incidence in the UK is in those aged 80-84
      years. Gout is associated with comorbidities such as nephrolithiasis, chronic
      renal impairment, metabolic syndrome, depression and heart disease. It is also
      associated with increased mortality. Untreated gout can result in disabling
      irreversible peripheral joint damage and chronic usage-related pain. However,
      gout is curable. The pathogenic agents that cause gout i.e.urate crystals can be
      eliminated through a combination of effective patient education and evidence
      based, targeted urate-lowering therapy. Gout is caused by the precipitation of
      monosodium urate crystals in and around a joint. The crystals preferentially form
      in peripheral, cooler joints and especially in those with osteoarthritis. It is
      thought that some of these preformed crystals within articular cartilage spill
      over into the joint space and trigger an acute attack of inflammation. Uric acid
      is predominantly renally excreted and the common heritable component of gout
      results from relative inefficiency of urate excretion. Chronic kidney disease,
      metabolic syndrome and drugs that reduce renal function (e.g. thiazide diuretics,
      beta-blockers and ACE inhibitors) will all lead to reduced elimination. Patients
      with chronic gout can present with monoarthritis but more commonly present with
      asymmetrical polyarthritis or tophi. Joints affected by osteoarthritis are
      preferentially targeted, the most common sites of involvement are feet, knees,
      hands and elbows. Diagnosis can be confirmed in primary care by taking a good
      history and clinical examination. An acute peripheral monoarthritis which reaches
      its peak within 24 hours and causes 'the worst pain ever experienced' is
      characteristic of an acute attack. A patient may have co-existing risk factors
      for gout such as osteoarthritis, obesity, hypertension, renal impairment,
      diuretic and antihypertensive drug use or increased beer or spirit consumption. A
      raised serum uric acid can confirm the diagnosis, however, this can be normal in
      the acute phase. Radiographs are rarely helpful but joint ultrasound may
      demonstrate deposits in cartilage, the synovium and peri-articular sites.

PMID- 25603589
TI  - Early treatment of psoriatic arthritis improves prognosis.
AB  - Psoriatic arthritis (PsA) is a chronic, autoimmune disease, affecting up to 1% of
      the adult population and up to 40% of those with psoriasis. There is no
      universally accepted definition or diagnostic criteria for the disease although
      the CASPAR classification of PsA is now the most widely used. PsA has a peak age
      of onset between 35 and 55 years with an equal gender distribution. Around 20% of
      patients develop PsA before psoriasis, often many years before skin or nail
      changes. Enthesitis, pain and tenderness at the insertion of any tendon onto the
      bone, is characteristic and screening for enthesitis should include palpation of
      the lateral epicondyle of the humerus, the medial condyle of the femur and the
      achilles tendon insertion. Diagnosis of PsA relies on a detailed history,
      particularly as many of the manifestations may be mild or transient, and
      therefore not reported by the patient. There may be a previous, current, or
      family history of psoriasis. There are no diagnostic blood tests for PsA. The
      presence of rheumatoid factor or anti-CCP antibodies does not preclude a
      diagnosis of PsA, but should prompt careful scrutiny of the diagnosis. X-rays of
      the hands and feet should be performed at baseline for all those with suspected
      inflammatory arthritis. Features of back pain that suggest an inflammatory cause,
      rather than a mechanical problem, include the presence of early morning stiffness
      and pain that is relieved by exercise and exacerbated by rest. Any patient with
      suspected inflammatory arthritis and a six-week history of painful, swollen
      joints should be referred for specialist assessment. Patients with PsA have a
      higher self-rated disease severity than those with psoriasis only and a 60%
      higher risk of premature mortality than the general population, their life
      expectancy is estimated to be approximately three years shorter. Aggressive
      treatment of early stage progressive PsA can substantially improve the long-term
      prognosis.

PMID- 25603590
TI  - End of year photo quiz. Test your diagnostic skills.

PMID- 25603591
TI  - The psychic factor in insomnia. 1914.

PMID- 25603592
TI  - The healing power of the magic sponge.

PMID- 25603593
TI  - [Effects of exercise and diet intervention on oxidative stress in insulin
      resistant rat].
AB  - OBJECTIVE: To investigate the effects of exercise, diet and their combination
      intervention on oxidative stress of insulin resistance rat. METHODS: Establish
      obesity-induced insulin resistance rat models. Obesity was assessed by the body
      weight and lipid ratio. Glucose tolerance was assessed by the integrated area
      under the curve for glucose (AUCg) during an oral glucose tolerance test (OGTT),
      then 8 weeks of exercise, diet, and combination interventions, respectively. To
      analyze serum free fatty acids (FFA) content, superoxide dismutase (SOD) and
      maleic dialdehyde (MDA) content in liver, adipose tissue and soleus muscle by
      biochemical method. Judge oxidative stressby FFA content and SOD/MDA. RESULTS:
      Three kinds of intervention reduced the body weight (P < 0.01), lipid ratio (P <
      0.01) and AUCg (P < 0.01). Dietary and combination intervention lowered serum
      free fatty acid concentration (P < 0.01), separate exercise intervention had not
      such effect. Three kinds of intervention increased SOD/MDA in the liver and
      adipose tissue, exercise and combination intervention improved SOD/MDA in soleus
      muscle, dietary intervention alone had not the effect. CONCLUSION: Exercise and
      dietary intervention may improve the overall insulin resistance by alleviating
      oxidative stress.

PMID- 25603594
TI  - [Prevalence of hyperglycemia and related factors among rural adults aged 35 years
      old and above in Yuhuan County, Zhejiang Province].
AB  - OBJECTIVE: To describe the prevalence of hyperglycemia among rural adults aged 35
      years old and above in Yuhuan, China. METHOD: A cross-sectional study was carried
      out as a baseline study of Rural Yuhuan Health Population Cohort in all
      communities in Yuhuan County, Zhejiang Province, China. A total of 125 479
      subjects aged 35 years old or above participated in this study to collect the
      general demographics and measure hypertension, fast glucose and etc. In SPSS
      16.0, non-conditional Logistic regression model was used for related factors
      analysis. RESULT: Among 118 274 eligible subjects, the average fasting glucose
      was (5.4 +/- 1.8) mmol/L and the average for men was higher than that for women.
      The crude prevalences of diabetes, impaired fasting glucose and hyperglycemia
      were 10.1%, 19.4% and 29.5%(the age and sex standardized one was 9.3%, 19.8% and
      29.1%), respectively. There were significant gender differences in both the
      average level of fasting glucose and the prevalence of hyperglycemia (P < 0.
      001). The prevalences of hyperglycemia varied statistically over different age
      groups from 19.9% in the lowest group of 35 - 39 years old to 36.4% in the
      highest group of 60 - 64 years old. In the non-conditional logistic regression
      model, age, sex, farmer, regular exercise, smoking, alcohol drinking and body
      mass index were related to hyperglycemia after the adjustment of other
      covariates. CONCLUSION: Hyperglycemia was common in adults aged 35 years old and
      above living in rural China.

PMID- 25603595
TI  - [Urinary iodine levels and its influencing factors among residents over age of 15
      years in Shenzhen City].
AB  - OBJECTIVE: To understand the status of iodine nutrition and the affective factors
      of urinary iodine concentration among residents over age of 15 years in Shenzhen
      City. METHODS: Totally 8152 residents from 73 communities were selected with
      stratified cluster random sampling. The morning urinary iodine was determined and
      the dietary assessment of iodine using a food frequency questionnaire were
      carried out. RESULTS: The range of urinary iodine was 9. 65 - 4039.09 MUg/L and
      the median of urinary iodine was 194.59 MUg/L among the residents. The
      percentages of the residents with urinary iodine < 50,50 - 100,100 - 199, 200 -
      300, and >= 300 MUg/L were 2.49%, 12.12%, 40.16%, 26.94% and 20.78%,
      respectively. There was significant difference in the medians of iodine between
      different gender (P = 0.0001), the medians of urinary iodine of men (201.32
      MUg/L) was slightly higher. There was no significant difference in urinary iodine
      levels (186.59 - 197.44 MUg/L) among all age groups, the medians of urinary
      iodine of all age groups were within the recommended adequate intake. Along with
      the increase in age, the medians of urinary iodine of all age groups was
      gradually decreased. Sex, alcohol consumption and daily dietary iodine intake was
      significant in the final regression model. CONCLUSION: The iodine nutrition of
      residents in Shenzhen City was in good condition, populations with low or high
      iodine still exist. The monitoring is needed and the influencing factors of the
      urine iodine levels need much exploration.

PMID- 25603596
TI  - [Effects of the SNPs on rs855791 and rs3811647 on the levels of SF and sTfR in
      the group of 8 - 14].
AB  - OBJECTIVE: To investigate effects on the levels of SF and sTfR by the SNPs of
      rs855791 on TMPRSS6 and rs3811647 on TF in adolescent. METHODS: DNA was extracted
      from venous blood which were drawn from 50 subjects, and then the two SNPs of
      each sample were identified by Sequenom MassArray. T test and chi-square test
      were selected to identify the relationship between the levels of SF and sTfR in
      each allele carriers, and then the effects of each SNP on the levels of SF and
      sTfR would be assessed. RESULTS: The level of SF of A allele carriers on rs855791
      (54.0 +/- 28.2 ng/ml) was higher than GG carriers (33.1 +/- 20.2 ng/ml) (P <
      0.05), and the discrimination of the level of sTfR between each allele carrier
      was not observed. The discriminations of the different levels of SF and sTfR
      among each SNP on rs3811647 were not observed. CONCLUSIONS: The level of SF may
      be affected by the SNP of rs855791 on TMPRSS6, and the effect of rs3811647 on TF
      may be weakened by the former one.

PMID- 25603597
TI  - [Effects of 10% Liuyangmycin emulsifiable on mitochondrial function in L-02
      hepatocytes].
AB  - OBJECTIVE: To investigate the effects of 10% Liuyangmycin emulsifiable (LY-EC) on
      mitochondrial function in L-02 hepatocytes. METHODS: To detect the effect of
      different concentration of LY-EC (0 -200 mg/L) on L-02 hepatocytes survival rate
      with MTT method, and choose proper LY-EC treated concentrations (survival rate >
      70%) for the following experiments. After hepatocytes were treated with LY-EC at
      0.39, 1.56, 6.25 and 25.00 mg/L respectively for 12 h, MDA and GSH contents, SOD,
      SDH, ATPase activities were respectively analyzed by their assay kits using
      colorimetry. Then mitochondrial PTP open percentage and the contents of ATP, ADP
      and AMP were measured with HPLC assays, and ATP/ADP ratio and energy charge (EC)
      values were calculated. The effects of LY-EC on mitochondrial ultra-structures
      were observed by transmission electron microscopy. RESULTS: LY-EC induced the
      decrease of cell survival rates in a concentrate- dependent manner (r = 0.939, P
      < 0.05). Compared with control group, GSH contents and SOD, SDH and ATPase
      activities in groups treated with LY-EC decreased significantly, MDA contents and
      mitochondrial PTP open percentages increased (P < 0.05), the levels of cellular
      ATP, TAN and ATP/ADP ratio in L-02 hepatocytes decreased, while energy charge
      (EC) increased significantly (P < 0.05). Hepatocytes treated with LY-EC were
      observed cytoplasmic edema, mitochondria swelling and the deformation of
      mitochondrial cristae with transmission electron microscope. CONCLUSION: LY-EC
      induced oxidative stress, mitochondrial function damage and energy metabolism
      disorder in L-02 hepatocytes.

PMID- 25603598
TI  - [Study on expression of functional proteins related with Schwann cell of rats in
      acrylamide exposure and convalescent].
AB  - OBJECTIVE: To explore the changes of four functional proteins which are related
      to Schwan cells (SCs), including myelin-associated glycoprotein (MAG), nerve
      growth factor (NGF), p75 neurotrophin receptor (p75NTR) and neural cell adhesion
      molecule (NCAM) on damage and repair of peripheral nerve induced by acrylamide
      (Acr). From the changes of the protein level, some meaningful information for the
      mechanism of Acr neurotoxicity and the screening of biomarkers might be acquired.
      METHODS: Rats were administrated with Acr at dose of 7. 5, 15 and 20 mg/kg by
      intraperitoneal injection for 3 weeks, high-dose group were observed for 4 weeks
      after 3 weeks exposure of Acr to create an animal model of peripheral nerve in
      injury and repair. Protein level of MAG, p75NTR, NGF and NCAM in rat sciatic
      nerve at the end of exposure and convalescent were measured by western blot. The
      level of MAG in plasma at the end of exposure and convalescent was measured by
      ELISA. RESULTS: (1) Rats treated with Acr appeared peripheral nerve damage
      symptom and began to recover after 4 weeks. The abnormal symptoms in female group
      were heavier than that of males, especially the high dose group. (2) Compared
      with the control group, the level of MAG decreased in the medium dose group and
      high dose group (P < 0.05), the level of p75NTR increased in high dose group (P <
      0.05). There were no significant changes in the level of NGF between the control
      group and treated groups of male rats. Compared with the male control group, the
      level of NCAM in the the high dose group increased (P < 0.05). (3) Compared with
      the control group, the level of plasma MAG in the high dose group decreased (P <
      0.05), while that in the recovery group was slightly increased. CONCLUSION: The
      changes of those functional proteins may reflect the state of the peripheral
      nerve damage induced by Acr. The downregulation of MAG in rat plasma may be
      related with that in sciatic nerve.

PMID- 25603600
TI  - [Development and application of Caco-2 cell lines transfering model for assessing
      the bioavailability of mycotoxins].
AB  - OBJECTIVE: The Caco-2 cell model for assessing the bioavailabilities of
      mycotoxins was developed and validated. METHODS: The Caco-2 monolayer cell
      transferring model was developed and validated by optimizing the initial
      concentrations of toxins in the apical side, the temperature and pH values of the
      experiment system, and the presence of mycotoxin adsorbent. RESULTS: The apparent
      permeability coefficient (Papp) of AFB1 reached the highest when pH value was in
      the range between 7.4 and 7.5, while the Papps for DON, AFB2, AFG1 and AFG2 were
      at the highest in the pH value between 7.0 and 7.1, respectively. The
      permeabilities of these five mycotoxins were increasing along with the
      temperature ascending. The transmicivities of AFB1, AFG1 and AFG2 reached the
      highest at the incubation time of 60 minutes but 120 minutes for DON and AFB2.
      CONCLUSION: The developed Caco-2 transferring model of the five mycotoxins was
      susceptible, stable, effective and reproducible.

PMID- 25603599
TI  - [MAPK signaling pathways involved in aluminum-induced apoptosis and necroptosis
      in SH-SY5Y cells].
AB  - OBJECTIVE: To explore the role of MAPK signaling pathway in apoptosis and
      necroptosis induced by aluminum in SH-SY5Y cells. METHODS: To imitate neural cell
      death induced by aluminium, AlCl3 x 6H2O (4 mmol/L) was used to treat SH-SY5Y
      cells. Necrostatin-1 (Nec-1,60 MUmol/L), the specific inhibitor for necroptosis,
      and zVAD-fmk (20 MUmol/L), the specific inhibitor for apoptosis, were added into
      cultures for inhibiting the occurrence of necroptosis and apoptosis. CCK-8 was
      performed to measure cell viability, flow cytometry was used to test the
      difference of apoptosis rate and necrosis rate between groups, and western-blot
      was used to detect the change of MAPK protein. RESULTS: Compared with blank
      control group, solvent control group, Nec-1 control group and zVAD-fmk control
      group, cell viabiligy of Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+)
      plus zVAD-fmk group decreaced (P < 0.05). Compared with Al(3+) exposed group,
      cell viability of Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group
      increased (P < 0.05). Necrotic rate and apoptotic rate in Al(3+) exposed group,
      Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group obviously increased
      compared with blank control group, solvent control group, Nec-1 control group and
      zVAD-fmk control group (P < 0.05). Compared with Al(3+) exposed group, necrotic
      and apaptotic rate of Al(3+) plus zVAD-fmk group and Al(3+) plus Nec-1 group were
      statistically significant decreased (P < 0.05). Compared with blank control
      group, solvent control group, Nec-1 control group and zVAD-fmk control group,
      expression of p-p38 in Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+)
      plus zVAD-fmk group increased obviously (P < 0.05), and expression of p-ERK
      decreased significantly (P < 0.05). Compared with Al(3+) exposed group,
      expression of p-p38 decreased (P < 0.05), but p-ERK increased in Al(3+) plus Nec
      1 group (P < 0.05). CONCLUSION: The ERK and p38 MAPK signaling pathways are
      involved in aluminum-induced necroptosis in SH-SY5Y cells, but only ERK signaling
      pathway is involved in aluminum-induced apoptosis, and JNK signaling pathway is
      not involved in aluminum-induced cell death.

PMID- 25603601
TI  - [Effects of different intakes of protein on nutritional status in severe stroke
      patients].
AB  - OBJECTIVE: To investigate the effects of different intake of protein on
      nutritional indicators in severe stroke patients. METHODS: 89 patients with
      severe stroke and NRS-2002 scores not less than 3 were enrolled. The patients
      were divided into group A, group B and group C by random, and 28 cases were in
      group A with protein intake at 0.9 g/kg, 30 cases were in group B with protein
      intake at 1.2 g/kg and 31 cases were in group C with protein intake at 1.6 g/kg,
      all patients were given the same calories support (25 kcal/kg). On the day of pre
      intervention, the 7th and 14th day of post-intervention, fasting blood samples
      were collected from every subjects. The total protein (TP), albumin (ALB),
      hemoglobin (Hb), creatinine (Cr), blood urea nitrogen (BUN), midarm circumference
      (MAC) and calf circumference (CC) were recorded. RESULTS: (1) The MAC and CC of
      health side body decreased on the 14th day post-intervention in group A and group
      B, the differences were significant compared with pre-intervention and on the 7th
      day post-intervention (P < 0.05), but there were no statistical differences
      between group A and group B. The index of group C had no significant changes from
      pre-intervention to the 14th day post-intervention. The differences among the
      three groups were statistically significant on the 14th day post-intervention (P
      < 0.05). (2) TP, ALB and Hb in group A were decreased from pre-intervention to
      the 14th day post-intervention, the differences were statistically significant.
      The levels of TP and Hb decreased in group B during the observation period, the
      differences were statistically significant. ALB in group B was decreased on the
      7th day post-intervention, but it was increased on the 14th day post
      intervention, there was no statistical difference compared with pre-intervention.
      The levels of TP, ALB and Hb in group C had no significant differences on the 7th
      day post-intervention, but they all increased on the 14th day post-intervention.
      The differences of ALB and Hb in group C were statistically significant on the
      14th day post-intervention compared with pre-intervention and on the 7th day post
      intervention. The differences of TP, ALB and Hb among the three groups were
      statistically significant on the 14th day post-intervention. (3) Cr in the three
      groups did not have significant differences during the observation period. BUN of
      group A and group B were both increased post-interventinon, the differences were
      statistically significant compared with pre-intervention and there were
      statistically significant differences between group A and group B (P < 0.05). BUN
      in group C did not have significant changes during the observation period. On the
      14th day post-intervention, the differences of BUN were statistically significant
      among the three groups (P < 0.05). CONCLUSION: The nutritional effect of protein
      intake at 1.6 g/kg is better than 0.9 g/kg and 1.2 g/kg on improving the
      nutritional status in severe stroke patients.

PMID- 25603602
TI  - [Contaminant levels and drug resistance analysis of Salmonella isolated from
      broiler production and processing course in Shandong Province in 2012].
AB  - OBJECTIVE: To investigate the Salmonella contamination and its antibiotic
      resistance spectrum in the whole process of broiler hatching, cultivation,
      slaughtering, processing, distribution and retail in Shandong Province. METHODS:
      2496 samples were collected from the chicken farms, hatching factory, breeding
      farm, slaughterhouse, large supermarkets and farmers' market in Jinan and Zibo
      City. All samples were tested according to GB 4789.4-2010 and the antimicrobial
      susceptibilities by the broth microdilution method. RESULTS: The positive rate of
      the hatching process was 2.39%, the breeding process was 12.67%, the slaughter
      process was 27.00%, the distribution and retail process was 22.72%. There were 32
      serotypes, the Indiara and Enteritidis Salmorella accounted for 42.25% and 34.21%
      respectively. 95.91% of the Salmorella strains were resistant to at least one
      antibiotic, 71.37% of the strains were resistant to at least three antibiotics,
      28.21% of the strains were resistant to at least ten antibiotics, 7 strains were
      resistant to fourteen antibiotics, all of them are Indiana Salmonella.
      CONCLUSION: In Jinan and Zibo City, it is seriously contaminated by various
      aspects of Salmonella in broiler production and processing. The contamination
      rate of slaughter and Salmonella distribution is higher than the links of
      hatching process and breeding. The situation of broiler Salmonella is becoming
      severe.

PMID- 25603603
TI  - [Investigation of urinary cadmium characteristics of the general population in
      three non-cadmium-polluted rural areas in China].
AB  - OBJECTIVE: To investigate the characteristics of urinary cadmium of the non
      occupational-cadmium-exposed population in non-cadmium contaminated rural area in
      China. METHODS: Randomly selected non-occupational cadmium exposed population
      2548 people (male 1290, female 1258) with each gender and age groups,
      questionnaire surveyed and collected random urine. Urinary cadmium and urinary
      creatinine (Cr) concentration were tested, excluding urinary Cr < 0.3 g/L and > 3
      g/L. Analyze the impact factors of urinary cadmium and calculated 95% quantile
      (P95) of urinary cadmium after correction by urinary Cr. RESULTS: Urinary cadmium
      increased with age and showed an upward trend. The urinary cadmium of the
      population of >= 30 years old was significantly higher than that of < 30 years
      old, women significantly higher than male, and smokers significantly higher than
      non-smokers (P < 0.01). Generalized linear model for multivariate analysis showed
      that smoking, age and gender are still significantly affected on urinary cadmium
      after adjusting for other factors (P < 0.01), regression equation: urinary
      cadmium (Cr corrected) = 0.854 + 0.325 x smoking + 0.111 x age--0.305 x gender (F
      = 367.69, P < 0.01). However, the multiple correlation coefficient of regression
      equation R2 = 0.0350, which is only 3.50% available in urinary cadmium variations
      can be explained by gender, age, and smoking. According to gender, smoking and <
      30 and >= 30 years of age, analysis the upper limit of cadmium in urine, the 95%
      upper limit of urinary cadmium of >= 30 year-old female smokers (13.47 MUg/g Cr)
      was significantly higher than other populations (< 6.0 MUg/g Cr), the 95% upper
      limit of urinary cadmium of >= 30 year-old female and >= 30 year-old male smokers
      exceeded the urinary cadmium limits (5 MUg/g Cr) of the occupational cadmium
      poisoning diagnostic criteria in China (GB Z17-2002). CONCLUSION: The urinary
      cadmium reference value of non-occupational-cadmium-exposed populations is < 6.0
      MUg/g Cr in the three non-cadmium contaminated rural area in China, but for
      smoking women over 30 year-old it needs more research to explore.

PMID- 25603604
TI  - [Study on tetrodotoxin detection and toxic puffer fish identification of roasted
      fish fillet at the retail in Beijing and Qingdao].
AB  - OBJECTIVE: The roasted fish fillet sample at the retail collected in Beijing and
      Qingdao were detected for TTX, and the TTX positive samples was analyzed for fish
      species identification. METHODS: TTX was tested by EUSA method and the cytochrome
      c oxidase I (COI) genome of TTX-positive samples was extracted and identified by
      DNA barcode. RESULTS: Totally, 90 samples were tested by EUSA and 58 (64.4%)
      samples were positive for TTX with the levels ranging from 0.10 mg/kg to 63.81
      mg/kg. Among the TTX positive samples, 24 (41.3%) were identified containing
      toxic puffer fish and 21 (87.5%) were Lagocephalus lunaris, the highly toxic
      puffer fish. CONCLUSION: Some roasted fish fillet samples obtained from the
      retail in two cities were positive for TTX and contained toxic puffer fish. Based
      on these results, we suggest that roasted fish fillet producers should prevent
      toxic puffer fish from mixing in the raw material and the I regulators should
      strengthen the TTX surveillance and product labeling supervision of roasted fish
      fillet.

PMID- 25603605
TI  - [Composition and distribution patterns of rare earth elements in Fujian teas].
AB  - OBJECTIVE: To investigate the composition and distribution pattern of rare earth
      elements in the teas from Fujian province. METHODS: A total of 145 samples of
      nine varieties of the teas were collected from their plantation fields and
      markets in Fujian province. The concentrations of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb,
      Dy, Ho, Er, Tm, Yb, Lu and Y in the samples were determined by inductively
      coupled plasma-mass spectrometry (ICP-MS). RESULTS: The concentrations of total
      REEs, light REEs (LREEs) and heavy REEs (HREEs) in the teas were 2.483, 1.764,
      0.720 mg/kg, respectively. The LREE was dominant with the highest concentration
      of Ce. The distribution pattern of the REE contents in the teas and corresponding
      plantation soils were similar. CONCLUSION: After the chondrite-nomalized
      distribution treatment, it was found that the REEs in the Fujian teas had a
      similar pattern with those of the soils in the Fujian province and Mainland
      China, and also with those in the green tea from Jiangsu province. However, the
      high concentrations of REEs in some Fujian teas should be paid with more
      attention and investigation.

PMID- 25603606
TI  - [Proliferation inhibition and apoptosis induction of Juglone on human cervical
      cancer Caski cells].
AB  - OBJECTIVE: To explore the effects of Juglone on proliferation and apoptosis of
      human cervical cancer Caski cells, and to further study the related mechanism of
      cell apoptosis. METHODS: Cultured Caski cells were incubated with 20, 40, 60, 80
      and 100 MUmol/L juglone for 24 h. The proliferation of Caski cells was detected
      by methyl thiazolyl tetrazolium (MTT) assay. The cell apoptosis were detected by
      transmission electron microscope. The expression of Bcl-2 and Bax were detected
      by Western blot. RESULTS: MTT results showed that in different doses of juglone
      groups, the Caski cell growth was greatly inhibited (P < 0.05, P < 0.01) and
      showed dose dependent when compared with control group except 20 MUmol/L. The
      IC50 of juglone was 42.4 MUmol/L. After treatment on Caski cells with 40 MUmol/L
      juglone, typical apoptosis characteristics was observed by transmission
      electronmicro scope. The expression of Bcl-2 was decreased while the expression
      of Bax was increased significantly when compared with control group (P < 0.05).
      CONCLUSION: Juglone significantly inhibits the proliferation and induces the
      apoptosis of Caski cells in vitro.

PMID- 25603607
TI  - [Effects of bisphenol A exposure during lactation on testicular mitochondria in
      male mouse offspring].
AB  - OBJECTIVE: To study whether maternal bisphenol A (BPA) exposure during lactation
      stage will induce oxidative stress and apoptosis in male offspring's testis by
      mitochondrial pathway. METHODS: After delivery, maternal mice were randomly
      divided into four groups, including high dose group (50 mg/kg), medium dose group
      (5 mg/kg), low dose group (0.01 mg/kg) and solvent control group. BPA were given
      daily by gavage to maternal mice during lactation stage. The pups were raised and
      sacrificed at PND 75. The effect of BPA exposure on the activity of testicular
      mitochondrial succinate dehydrogenase (SDH), superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in male offspring were
      detected. The expressions of cytochrome C (Cyt C), caspase 3 and apoptosis
      inducing factor (AIF) in testes of male offspring were detected by Western blot.
      Changes of mitochondrial substructure in testicular cells were observed by
      transmission electron microscopy. RESULTS: The exposed mice had a significant
      decrease in the activities of testicular mitochondrial SDH (P < 0.05) in all
      groups and with notable decrease in the activities of GSH-Px and SOD in the high
      and medium-dose groups (P < 0.05). BPA also caused testicular mitochondrial MDA
      increased markedly (P < 0.05). Western blot showed that the expression levels of
      Cyt C, caspase 3 and AIF increased significantly in the testes of BPA-treated
      groups (P < 0.05). Under transmission electron microscopy, mitochondria swell,
      crests obscure and disappear were founded in the high and medium-dose groups.
      CONCLUSION: During lactation stage, maternal exposed to BPA induce oxidative
      stress and apoptosis of testicular cells by possible mechanisms of mitochondrial
      pathway,which would cause adverse effects on the early development of testis.

PMID- 25603608
TI  - [Effects on expression of osteogenesisgene in the osteoblast with endoplasmic
      reticulum stress induced by fluoride].
AB  - OBJECTIVE: To explore the gene expressions of endoplasmic reticulum stress and
      differentiation in osteoblast treated by excess fluoride. METHODS: Using primary
      cultured human osteoblasts for fluorosis model in vitro, apoptosis was inspected
      by flow cytometer, and RNA was extracted for examination of the unfolded protein
      response and bone differentiation genes. RESULTS: Fluoride could cause endoplasm
      reticulum stress in osteoblasts by 15 genes upregulated, 1 gene downregulated.
      These genes involved PERK, IRE1 and ATF6 signaling pathways of endoplasmic
      reticulum stress. Meanwhile 32 osteogenesis genes were upregulated, and 2 genes
      downregulated, involving collagen, matrix metalloproteinase, integrin, bone
      morphogenetic protein, vascular endothelial growth factor, and tumor necrosis
      factor gene. CONCLUSION: Excess fluoride can cause endoplasmic stress in
      osteoblast, while have an impact on the gene expression of osteogenesis.

PMID- 25603609
TI  - [Changes of 4 trace elements in peripheral blood of rats by respiratory
      exposure].
AB  - OBJECTIVE: To investigate the effects and changes of Hg, I, Mn and Sr in
      peripheral blood (whole blood, plasma, erythrocytes and peripheral blood
      mononuclear cells (PBMCs) of rats by inhalation exposure. METHOD: 32 SD rats were
      divided randomly into 4 groups including one control group and three intervention
      groups. Each rat in three intervention groups was exposed respectively to three
      different doses of mixed elements (Hg, I, Mn, Sr) solution by intratracheal
      instillation for 10 days. The whole blood of all rats were collected from arteria
      femoralis and separated into three parts by Percoll. The concentrations of 4
      trace elements (Hg, I, Mn, Sr) in whole blood, plasma, erythrocytes and PBMCs
      were determined by inductively coupled plasma mass spectrometry (ICP-MS). RESULT:
      With the increasing of exposure doses, concentrations of 4 elements in whole
      blood and plasma tended to increase. No significant differences of Mn and Sr were
      found in erythrocytes (P > 0.05), while concentrations of I and Hg tended to
      increase with the increasing of exposure doses. No significant differences of Mn
      and I in PBMCs (P > 0.05) were found in the 4 groups, while concentration of Hg
      tended to increase with the increasing of exposure dose. CONCLUSION: The elements
      concentrations in whole blood and plasma can reflect the influence of inhalation
      exposure, while the concentrations of some elements in erythrocytes and PBMCs are
      barely influenced by inhalation exposure doses.

PMID- 25603610
TI  - [High performance liquid chromatography coupled with electrospray tandem mass
      spectrometry for the analysis of dicyandiamide and melamine residues in milk and
      milk products].
AB  - OBJECTIVE: To establish a sensitive method for the analysis of dicyanodiamide and
      melamine residue in milk and milk products by, hydrophilic interaction liquid
      chromatography coupled with electrospray tandem mass spectrometry. METHODS:
      Samples were extracted with 2.5% (V/V) formic acid solution. Acetonitrile was
      used to precipitate proteins. The separation was carried on Acquity UPLC BEH
      Amide column (100 mm x 2.1 mm x 1.7 mm) by gradient elution with acetonitrile -
      water as mobile phase. Identification was achieved by electrospray ionization
      (ESI) in positive mode using multiple reaction monitoring, and quantified with
      external standards. RESULTS: The dicyanodiamide and melamine were linear in the
      range of 5.0 - 1000.0 MUg/L with correlation coefficient of 0.9995 for
      dicyanodiamide and 0.9997 for melamine. The detection limit of the method were
      10.0 MUg/kg for dicyanodiamide and melamine. The spiked at three levels ranged
      86.0% - 100.0% (0.050 mg/kg), 90.0% - 104.0% (1.0 mg/kg) and 90.0% - 100.1% (10.0
      mg/kg). And the relative standard derivations were lower than 1.06% -7.77%. The
      within-day precisions were 2.35% (dicyanodiamide) and 3.44% (melamine), and the
      inter-day precision 3.87% (dicyanodiamide) and 5.39% (melamine). CONCLUSION: The
      method was sensitive, accurate and precise. It can be used in monitoring quality
      of milk production and daily analysis of milk and milk products.

PMID- 25603611
TI  - [Antimony film-plated glassy carbon electrode for simultaneous determination of
      trace lead and cadmium in urine by differential pulse stripping voltammetry in
      the presence of cetyltrimethylammonium bromide].
AB  - OBJECTIVE: To investigate and optimize the experiment conditions of determining
      lead and cadmium simultaneously with antimony film-plated glassy carbon
      electrode. METHODS: CTAB was used as sensitizer, and antimony film-plated glassy
      carbon electrode was prepared by in-situ plating for the determination of trace
      lead and cadmium by differential pulse stripping voltammetry. RESULTS: Under
      optimized conditions, well defined peaks of lead and cadmium were obtained at the
      potential of -0.48 V and -0.73 V respectively. Following a 180 s
      preconcentration, the stripping peak currents changed linearly with the
      concentration of lead and cadmium over the range from 0 to 100 MUg/L (r >=
      0.991). The detection limits of lead and cadmium were 0.47 MUg/L and 0.78 MUg/L.
      The average recoveries were 92.0% - 104.3% and 94.0% - 102.6% respectively, with
      the relative standard deviations no more than 6.1%. The method was applied to the
      determination of lead in urine, and the results were satisfactory. CONCLUSION:
      The method has high sensitivity, good precision and accuracy. Antimony film
      electrode could be used for another new environment-friendly membrance electrode
      for determination of lead in human urine samples instead of mercury film
      electrode.

PMID- 25603612
TI  - [UPLC-MS/MS method for the determination of icaritin in rat plasma].
AB  - OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) method for the quantification of icairitin (ICT), and
      investigate pharmacokinetics of ICT in rats following a single intravenous
      administration. METHODS: ICT and an internal standard coumestrol (CMT) were
      extracted from rat plasma using acetonitrile and separated on a BEH C18 column
      (2.1 mm x 50 mm, 1.7 MUm) using a gradient mobile phase of acetonitrile, water,
      ammonium formate and formic acid at a flow rate of 0.3 ml/min. At negative
      electrospray ionization mode, multiple reaction monitoring of the precursor
      product ion transitions of m/z 367.1-->297.1 for ICT, 267.0 --> 211. 1 for CMT
      was used for the quantification. Plasma was collected after rats were
      intravenously administered with ICT at a single dose of 10 mg/kg. RESULTS: The
      linear calibration curve was obtained in a concentration range of 0.5 - 20 ng/ml
      with a lower limit of quantification of 0. 5 ng/ml. The value of intra- and inter
      day precision was less than 8.1% and accuracy fell in the ranges of 95.3% -
      99.3%. The recovery ranged from 90.1% to 92.1% and the matrix effects from 97.5%
      to 101.2%. After intravenous administration of ICT to rats, t1/2 was(1.13 +/-
      0.32) h, V was(4.54 +/- 0.27) L/kg, and CL was (2.91 +/- 0.68) L/(h x kg).
      CONCLUSION: The method was rapid, specific and accurate, suitable for preclinical
      pharmacokinetics of ICT.

PMID- 25603613
TI  - [Systematic review of university teachers' mental health based on SCL-90].
AB  - OBJECTIVE: To review the overall situation of university teachers' mental health
      in China systematically. METHODS: The literatures using Symptom Check List 90 to
      study university teachers' mental health in the databases during 2004 - 2014 were
      searched. WMD was taken as the index of effect size, and meta-analysis was
      carried to study the difference of mental health between university teachers and
      norm of China, also within different genders and titles. RESULTS: 56 qualified
      literatures were included. The university teachers' total score, and the score of
      interpersonal sensitivity factor, anxiety factor, photic anxiety factor were
      higher than the norm of China, WMD were respectively 11.24, 0.21, 0.16 and 0.22.
      Male teachers' total score (-3.86), and the score of somatization (-0.07),
      depression (-0.06), anxiety (-0.07), photic anxiety (-0.06) were lower than
      female's. The score of primary title teachers interpersonal sensitivity (-0.09),
      photic anxiety (-0.10) were lower than intermediate title teachers'. The score of
      primary title teachers somatization (-0.19), obsessive-compulsive (-0.13),
      interpersonal sensitivity (-0.12), depression (- 0.12), anxiety (-0.10), paranoid
      ideation (-0.12), psychoticism (-0.09) were lower than senior vice title
      teachers'. The score of primary title teachers somatization(-0.23), depression (
      0.16) were lower than senior title teachers'. CONCLUSION: The mean level of
      university teachers' mental health was lower than the norm of China. The overall
      situation of university teachers' mental health in China was not optimistic. The
      society and school should take targeted measures to improve university teachers'
      mental health.

PMID- 25603614
TI  - [Meta analysis of condiments fortified with sodium iron
      ethylenediaminetetraacetate on the prevention and treatment of anemia].
AB  - OBJECTIVE: To evaluate the effect of condiments fortified with sodium iron
      ethylenediaminetetraacetate (NaFe-EDTA) on the prevention and treatment of
      anemia. METHODS: The randomized controlled trials about condiments fortified with
      NaFe-EDTA on the prevention and treatment of anemia were collected in such
      databases as The Cochrane Library, MEDLINE, EMbase, WHOLIS, EBSCO, HighWire
      Press, PubMed, CNKI, WanFang Data, VIP and CBM. Data were evaluated with the
      method of Cochrane systematic review by using RevMan 5.2.6. RESULTS: Seven
      randomized controlled trials were included. NaFe-EDTA fortification group
      increased hemoglobin level by 3.2 g/L (weighted mean difference, 95% CI 2.9 -3.5,
      P < 0.001) compared with control group. Subgroup analysis found that the clearest
      results of NaFe-EDTA fortification to prevent anemia is in school children (OR =
      0.4, 95% CI 0.2 - 0.5), the posterior of that is in child-bearing period women
      (OR = 0.5, 95% CI 0.4 - 0.6), while which has effect in preschool children but
      quite part of them were still unable to achieve the normal hemoglobin standard
      (OR = 0.7, 95% CI 0.4 - 1.0). CONCLUSION: Condiments fortified with NaFe-EDTA is
      able to improve hemoglobin level and prevent anemia. However, more evidences
      should be collected to evaluate the prevention effect in preschool children.

PMID- 25603615
TI  - [Meta analysis of the association between the expression of microRNA-155 and the
      outcome of patients with lung cancer].
AB  - OBJECTIVE: To evaluate the association between the expression of microRNA-155
      (miRNA-155) and the outcome of patients with lung cancer systemically. METHODS: 7
      case-control studies about the expression of microRNA-155 that were based on our
      inclusion criterion and available in the literature were reviewed from CBM disc,
      CNKI, VIP, Wanfang data SCIRUS, ASCO and ESMO. Meta-analysis was carried out by
      Stata 12.0 software. RESULTS: Seven studies were included into the researches and
      there were no biased among the studies. After deleting the significant
      heterogeneity study, it showed significant association between the high
      expression of microRNA-155 and the outcome of patients with non-small cell lung
      cancer with the merged HR was 1.48 with 95% CI 1.07-2.06. CONCLUSION: The current
      paper on Meta-analysis demonstrated a correlation between the high expression of
      miRNA-155 and the outcome of patients with non-small cell lung cancer.

PMID- 25603616
TI  - The importance of being credentialed.

PMID- 25603617
TI  - Promoting safe hygiene practices in public restrooms: a pilot study.
AB  - The study described in this article examined the impact of hygiene posters in
      promoting safe hygiene practices for used toilet tissue disposal in public
      restrooms. Although the long-held hygiene norm in homes for the disposal of used
      toilet tissue in a container may occur in the rural U.S., it is critical in
      public environments to promote proper toilet tissue disposal in toilets to reduce
      potential transmission of bacteria and viruses. A control group time series
      design was used for observations of used toilet tissue disposal on the floor or
      in large trash cans in restrooms with and without signage for a two-week period.
      A significant decrease in observations was reported at intervention sites with
      posters (p = .025). No significant differences were reported at the control site.
      Posters were effective in motivating behavior change beyond hand hygiene. Further
      research may examine the impact of health posters in other environmental
      settings.

PMID- 25603618
TI  - Evaluation of five years of nursing home inspection forms: structural and hygiene
      related violation trends.
AB  - Health inspections are performed at nursing homes to identify and reduce risk and
      to help maintain a safe environment for nursing home residents. The study
      described in this article aimed to identify the most frequent violations, types
      of violations (hygiene or structural), and repeat violations in nursing home
      facilities during health inspections; and to determine if the age of the facility
      influenced inspection scores. Nursing home health inspection forms (N = 131)
      completed between 2005 and 2011 in Pitt County, North Carolina, were analyzed.
      Results indicated that 60% of all violations were hygiene-related and could
      possibly be corrected without significant financial investments by management.
      Significant correlations occurred between the total number of violations and the
      facility age (p = .003) and between the number of repeat violations and total
      violations (p < .001). The average inspection score for nursing homes could be
      increased by more than three points if sanitation practices were improved.

PMID- 25603619
TI  - Sanitation in classroom and food preparation areas in child-care facilities in
      North Carolina and South Carolina.
AB  - Approximately 60% of U.S. children aged five and younger spend time in child-care
      settings. Such environments increase the risk of diarrheal disease, including
      diseases caused by enteric pathogens. To describe adherence to sanitation
      standards in classrooms and food preparation areas in child-care facilities, the
      authors conducted site visits in 40 North Carolina and South Carolina child-care
      facilities. Audits in up to two classrooms (rooms providing care for infants and
      toddlers) and the kitchen were performed using a form similar to a regulatory
      inspection form. Audit data were used to calculate indices to describe adherence
      to sanitation standards and were based on state environmental health regulations
      for child-care centers, the Food and Drug Administration's Food Code 2009, and
      guidance from food safety experts. Most facilities participating in the authors'
      study adhered to sanitation standards within the classroom; however, deficiencies
      with regard to sanitation in food preparation areas and refrigerator operating
      temperatures were noted. These results provide insight into possible risk factors
      for enteric disease transmission in child-care facilities.

PMID- 25603621
TI  - An introduction to building agency capacity.

PMID- 25603620
TI  - Exposure to electric power generator noise among small scale business operators
      in selected communities in Ibadan, Nigeria.
AB  - Inadequate and erratic power supplies mean small businesses use electric
      generators for alternative power. The authors' goal in the study described here
      was to assess noise from electric generators and impacts in the commercial areas
      of Agbowo and Ajibode in Ibadan, Nigeria. Noise levels (A-weighted decibels
      [dBA]) were measured over 12 weeks, three times a day, during the 2010 dry season
      using a sound level meter. A questionnaire was administered (515 respondents; 304
      in Agbowo, 211 in Ajibode) and audiometric measurements were conducted on 40% of
      respondents. Mean noise levels varied by source (104 +/- 7.7 dBA [diesel], 94.0
      +/- 6.3 dBA [petrol]) and were highest midday (90.6 +/- 5.3 dBA [Agbowo], 70.9 +/
      6.2 dBA [Ajibode]). Mean noise levels in Agbowo (78.5 +/- 3.9 dBA) and Ajibode
      (65.7 +/- 4.4 dBA) exceeded World Health Organization guidelines (65 dBA) for
      outdoor commercial environments. Working and living in Agbowo was significantly
      associated with current evidence of hearing impairment (odds ratio: 6.8, 95%
      confidence interval: 3.4-13.7). Reducing exposure to noise from electric power
      generators serving urban small businesses and homes is warranted.

PMID- 25603623
TI  - Applying a general best practices identification framework to environmental
      health.

PMID- 25603622
TI  - Environmental odors web site: providing communities and health officials with the
      tools to address odor issues.

PMID- 25603624
TI  - "Situational futuring" and 44 mind-stretching scenarios to learn how to use it:
      the second 22.

PMID- 25603625
TI  - Percutaneous cholecystostomy: single centre experience in 111 patients with an
      acute cholecystitis.
AB  - PURPOSE: To evaluate the safety and long-term outcome of percutaneous
      cholecystostomy (PC) under radiologic guidance for acute calculous cholecystitis
      (ACC) and acute acalculous cholecystitis (AAC) in all patients undergoing that
      procedure at our institution. MATERIALS AND METHODS: We performed a retrospective
      analysis of 111 patients who underwent PC from 2004 to 2012. Patients were
      divided into two groups: AAC and ACC. For all patients, comorbidity and American
      Society of Anesthesiologists (ASA) classification were determined. The
      indications, complications, recurrence rate and long-term outcome for both groups
      were analysed. The mean follow-up was 55 months. RESULTS: Twenty-four patients
      with AAC and 87 patients with ACC underwent PC. The most common sonographic
      findings of ACC and AAC were gallbladder wall thickening (90.9%) and hydrops
      (72.9%). Twelve of 24 patients with AAC (50%) were hospitalized at the Intensive
      Care Unit (ICU). Overall, the procedure failed in 2 (1.8%) patients. There were 4
      (3.6%) abscesses and 2 (1.8%) fistulas post PC. Drain dislodgment was found
      without sequelae in 8 (7.2%) patients. Elective cholecystectomy was performed in
      35/111 (31.5%). Fifty-one of 87 (58.6%) patients with gallstones underwent
      cholecystectomy; 36/87 (41.3%) did not undergo surgery due to a too short follow
      up or death of nonbiliary disease. In the AAC group, there was no recurrent
      cholecystitis in 17/24 (70.8%) patients; 3/24 (12.5%) underwent surgery and 4/24
      (16.6%) patients died in the ICU. CONCLUSION: PC is a minimally invasive
      treatment with low complication rate for patients with acute cholecystitis whom
      considered being at high-risk for urgent cholecystectomy. Good selection (ASA III
      and IV) and indication is needed in patients with ACC before PC because the
      majority will be operated later on. AAC can be managed nonoperatively and further
      treatment might not be needed.

PMID- 25603627
TI  - Real time ultrasound guided pediatric percutaneous renal biopsy: the traditional
      method versus angled tangential approach.
AB  - AIM: The aim of the present study was to compare the success and complication
      rates of pediatric renal biopsy procedures between the angled tangential approach
      and the traditional approach. METHODS: From 2004 to 2009 we prospectively
      enrolled pediatric patients who had undergone real time ultrasound guided renal
      biopsy with angled tangential approach. For comparison, we retrospectively
      reviewed pediatric patients who had undergone traditional renal biopsy between
      2002 and 2004. Adequacy of renal tissue histopathological samples and the
      complication rates were compared between groups. RESULTS: One hundred twenty
      eight patients underwent traditional renal biopsy (Group A) while 166 patients
      underwent biopsy performed with angled tangential approach (Group B).The rate of
      inadequate material was higher in Group A compared to Group B (6.3% vs. 0.6%, p =
      0.006). In four cases (three in Group A and one in Group B) renal biopsies
      revealed normal renal tissue. While a major complication (hemoperitoneum
      requiring transfusion) occurred in one case in Group A, no major complications
      were seen in Group B. CONCLUSION: Compared with the traditional technique, the
      angled tangential approach resulted in a higher adequate material rate and lower
      complication rate.These findings indicate that angled tangential approach could
      be considered for pediatric percutaneous renal biopsies.

PMID- 25603626
TI  - How sensitive and specific are MRI features of sacroiliitis for diagnosis of
      spondyloarthritis in patients with inflammatory back pain?
AB  - OBJECTIVE: To determine the sensitivity and specificity of MRI features of
      sacroiliitis in spondyloarthritis (SpA). MATERIALS AND METHODS: A retrospective
      study reviewed MRI of the sacroiliac (SI) joints in 517 patients with
      inflammatory back pain. Sensitivity, specificity, positive and negative
      likelihood ratios of active and structural lesions of sacroiliitis with final
      clinical diagnosis as golden standard was calculated. RESULTS: MRI showed active
      inflammation in 42% of patients (bone marrow oedema (BMO) (41.5%), capsulitis
      (3.3%), enthesitis (2.5%)) and structural changes in 48.8% of patients (erosion
      (25%), fat infiltration (31.6%), sclerosis (32%) and ankylosis (7.6%)). BMO was
      the MRI feature with the highest sensitivity (65.1%) for diagnosis of SpA.
      Capsulitis (99%), enthesitis (98.4%), ankylosis (97.4%) and erosion (94.8%) had a
      high specificity for diagnosis of SpA, whereas BMO (74.3%), sclerosis (75.8%) and
      fat infiltration (84.0%) were less specific. BMO concomitant with enthesitis,
      capsulitis or erosions increased the specificity. Concomitant presence of BMO and
      sclerosis or fat infiltration decreased the specificity. CONCLUSION: BMO is
      moderately sensitive and specific for diagnosis of SpA in patients with
      inflammatory back pain. BMO concomitant with enthesitis, capsulitis, ankylosis or
      erosion increases the specificity. Concomitant fat infiltration or sclerosis
      decreases the specificity for diagnosis of SpA. Of all lesions, erosion had by
      far the highest positive likelihood ratio for diagnosis of SpA.

PMID- 25603628
TI  - Diffusion-weighted MR imaging: role in the differential diagnosis of breast
      lesions.
AB  - PURPOSE: To evaluate the diagnostic value of magnetic resonance diffusion
      weighted imaging (DWI) using apparent diffusion coefficient (ADC) values to the
      characterization of breast lesions and differentiation of benign and malignant
      lesions. MATERIALS AND METHODS: Thirty-seven women (mean age, 38 years) with 37
      enrolled in the study. DWI and ADC maps in the axial plane were obtained using a
      1.5 Tesla MRI device. Mean ADC measurements were calculated among cysts, normal
      fibroglandular tissue, benign lesions and malignant lesions were evaluated.
      RESULTS: Out of 37 women, 4 had normally breast MRI findings. The diagnosis of
      remaining 33 patients with 37 breast lesions were as follows; malign lesions (n =
      23), benign lesions (n = 10) and simple breast cyst (n = 4). The ADC values were
      as follows (in units of 10(-3) mm2/s): Normal fibroglandular tissue (range: 1.39
      2.06; mean: 1.61 +/- 0.23), benign breast lesions (range: 1.09-1.76; mean: 1.47
      +/- 0.25), cyts (range: 2.27-2.46, mean: 2.37 +/- 0.07) and malignant breast
      lesions (range: 0.78-1.26, mean: 0.96 +/- 0.25). The mean ADC obtained from
      malignant breast lesions was statistically different from that observed in benign
      solid lesions (p < < 0.01) and normal fibroglandular breast tissue (p < 0.01).
      Furthermore, the mean ADC values of benign breast lesions was not statistically
      different from cyst (p >= 0.01) and normal fibroglandular breast tissue (p >=
      0.01). A ADC value of 1.1 x 10(-3) mm'/s as a treshold value provided
      differantiation for malign and benign lesions, with a sensitivity of 91.3% and a
      specificity of 85.7% compared with conventional breast MRI values. CONCLUSION:
      DWI with quantitative ADC measurements is a reliable tool for differentiation of
      benign and malignant breast lesions.

PMID- 25603629
TI  - Mucocele of the appendix: case report and review of literature.
AB  - Mucocele of the appendix is a descriptive term of a distended, mucus-filled
      appendix caused by various conditions, both benign and malignant. Computed
      tomography is the imaging modality of choice. Correct pre-operative diagnosis is
      important because of the possibility of peroperative rupture and subsequent
      development of pseudomyxoma) peritonei. It is the task of the radiologist to
      alert the clinician and surgeon to the presence of this entity, the potential
      associated complications and possible signs of malignancy.

PMID- 25603630
TI  - Update on MRI of spondyloarthritis. part one: the sacro-iliac joint.

PMID- 25603631
TI  - Update on MR imaging of spondyloarthritis. part two: spine MR imaging.

PMID- 25603633
TI  - Small bowel angioedema induced by angiotensin converting enzyme (ACE) inhibitor:
      US and CT findings.
AB  - Small bowel angioedema induced by angiotensin converting enzyme (ACE) inhibitors
      is a rare and often-unrecog- nized condition that presents with transient
      abdominal pain, nausea and vomiting. We report a case diagnosed in a 36 year-old
      female. Ultrasound and CT showed segmental small bowel wall thickening and
      straightening associated with marked submucosal edema and ascites. Laboratory
      tests only revealed mild leukocytosis. The patient improved spontaneously.

PMID- 25603632
TI  - Capillary telangiectasia of the brain: imaging with various magnetic resonance
      techniques.
AB  - Brain capillary telangiectasia is an incidental vascular malformation found
      usually in pons and sometimes in extra- pontine sites. Typical MRI features are
      enhancement on post contrast T1 weighted images and signal loss on gradient echo
      images. We evaluated 10 patients with various MR techniques. Susceptibility
      weighted imaging was superior to GRE T2 in showing decreased signal due to
      susceptibility effects. Diffusion weighted imaging and diffusion tensor imaging
      proved not useful in the diagnosis.

PMID- 25603634
TI  - Added value of diffusion weighted MR imaging in the diagnosis of postpartum
      ovarian vein thrombosis.
AB  - Postpartum ovarian vein thrombosis (POVT) is a rare cause of right fossa pain but
      the diagnosis should be considered in the clinical setting of persistent fever
      and lower quadrant tenderness in the postpartum period. Although ultrasound is
      the initial step in the diagnostic work-up right fossa pain, it is often limited
      by overlying bowel gas and an enlarged puerperal uterus. Therefore, most authors
      recommend Computed Tomography (CT) as the imaging technique of choice to confirm
      the clinical suspicion of POVT. Because Magnetic Resonance Imaging (MRI) is less
      readily available, it is rarely performed for this indication. However, MRI
      allows not only to make the diagnosis as accurate as CT, but moreover it provides
      2 important advantages in compared to CT. First, it avoids ionizing radiation.
      Secondly, the use of diffusion weighted imaging (DWI) may obviate the
      administration of intravenous contrast.

PMID- 25603635
TI  - Angioleiomyoma in the soleus muscle.
AB  - We present a case of angioleiomyoma, a benign angiomatous soft tissue tumor in a
      52-year-old patient. We empha- size that small nodular tumors showing
      hypervascularity on MRI or ultrasound may be malignant and should be treated with
      tumor excision.

PMID- 25603636
TI  - Primary undifferentiated embryonal sarcoma of the liver misdiagnosed as hydatid
      cyst in a child: a case report and review of the literature.
AB  - Primary undifferentiated embryonal sarcoma (UES) of the liver is a highly
      malignant mesenchymal origin tumor and has a peak incidence between the ages of 6
      and 10 years. We hereby report a case of primary UES of the liver in a 7-year-old
      male patient who initially was misdiagnosed and treated as hydatid cyst of the
      liver. The tumor was occupying almost the entire right lobe of the liver and had
      a mostly cystic appearance with some solid components in it. Because hydatid
      disease is endemic in this region, it can often lead to misdiagnosis. The correct
      diagnosis was established after a biopsy and following neo-adjuvant chemotherapy
      the patient underwent a successful right hepatic lobectomy with complete
      resection of the tumor. The patient also received adjuvant chemotherapy and is
      currently disease-free in the present six month period. Primary UES of the liver
      has a predominantly solid appearance on US in contrast to its mostly cystic
      appearance on CT and MRI. These paradoxical imaging findings should be kept in
      mind in order to be able to distinguish this rare tumor from other entities,
      especially hydatid cyst. Thus, early diagnosis and prompt surgical resection of
      these tumors together with adjuvant and/or neo-adjuvant chemotherapy can provide
      complete remission.

PMID- 25603637
TI  - Appearance and vanishing of a spinal intradural arachnoid cyst after multiple
      epidural corticosteroid injections. A spontaneously resolving cause of
      symptomatic lumbar stenosis.
AB  - BACKGROUND: Spinal intradural arachnoid cyst is a rare lesion, sometimes
      acquired. PURPOSE: To describe the appearance and later spontaneous disappearence
      of a lumbar intradural arachnoid cyst, following perineural corticoid injections.
      METHOD: Review of the clinical data and imaging, with final spontaneous return to
      initial state. DISCUSSION: Atypical intradural arachnoid cysts can be related to
      perineural injections and can cause symptoms of spinal stenosis. Its spontaneous
      vanishing is a very rare event, up to now unreported.

PMID- 25603638
TI  - Hepatic angiosarcoma occurring 65 years after thorium dioxide (Thorotrast)
      exposure: imaging, surgical and histo- pathologic findings of a historical case.
AB  - We report the CT, surgical and histopathologic findings of a rare case of Hepatic
      Angiosarcoma (HAS) diagnosed in a 85-year old women 65 years afterThorotrast
      (Th232) exposure for angiography. At the early arterial phase of dynamic MDCT,
      peripheral curvilinear and central nodular puddling of contrast produced in the 8
      cm tumor.Then progressive contrast filling of the tumor was observed on the
      delayed scans. Associated pathognomonic signs related to previous Th232 exposure
      were also found comprising diffuse intrahepatic reticular bands of
      calcifications, numerous calcified epigastric lymph nodes and a calcified
      shrunken spleen. Emergency laparotomy was performed because of associated
      hemoperitoneum. With a delay of 65 years afterThorotrast exposure, this
      historical case probably represents, to our knowledge, the most delayed
      presentation of Th232 related HAS ever published.

PMID- 25603639
TI  - Fibrous pseudotumor of the tunica vaginalis: contrast enhanced sonography with
      pathologic correlation.
AB  - We report the case of a 28-year-old man who presented at the emergency department
      with recent left painful scrotal swelling, without history of genitourinary
      infection or trauma. On physical examination, left scrotal swelling with nodular
      palpation was noted. Contrast enhanced sonography demonstrated nodular
      vascularized thickening of the tunica vaginalis. Surgical exploration revealed
      multiples solid nodules of the vaginal wall, with, at frozen section analysis,
      fibroblastic tissue, vessels and chronic inflammation without malignity,
      suggestive of fibrous pseudotumor of the tunica vaginalis. We discuss the
      sonographic aspect of this rare entity and the difficulty to establish a diagno-
      sis of benignity without surgical exploration.

PMID- 25603641
TI  - Leiomyoma of the urinary bladder.

PMID- 25603640
TI  - An unusual presentation of a pelvic textiloma mimicking a tumor.

PMID- 25603642
TI  - Imaging findings in a patient with saliva in the auditory canal.

PMID- 25603643
TI  - MR imaging features of acute bilateral caudate infarcts in pregnant woman.

PMID- 25603644
TI  - Pseudo-achalasia: a complication of laparoscopic adjustable gastric banding.

PMID- 25603645
TI  - A case of acute appendicitis at atypical localization.

PMID- 25603646
TI  - Spontaneous osteonecrosis of the knee (SONK).

PMID- 25603647
TI  - US diagnosis of acute pancreatitis caused by ruptured hydatid disease to the
      biliary system.

PMID- 25603648
TI  - A Joe Beck story to tell.

PMID- 25603649
TI  - Hot yoga establishments in local communities serving pregnant women: a pilot
      study on the health implications of its practice and environmental conditions.
AB  - Hot yoga establishments have been increasing in popularity in local communities.
      Studios may support participation among pregnant women though no clinical studies
      currently exist that examine prenatal hot yoga effects. The pilot study described
      in this article aimed to assess the spread of prenatal hot yoga and to provide
      information on the environmental conditions and practices of those who engage in
      hot yoga within a local community. A thermal environment meter was used to
      measure ambient air conditions during three 90-minute hot yoga classes. Mothers
      who practiced prenatal hot yoga were more likely than non-hot yoga practitioners
      to have someone aside from an obstetrician/gynecologist discuss prenatal exercise
      safety with them. Prenatal public health education campaigns need to be refined.
      Public health officials and obstetricians/gynecologists need to be aware that
      those who engage in a hot yoga practice are more likely to trust someone other
      than their health care provider or public health professional regarding safety of
      this practice.

PMID- 25603650
TI  - O-chlorobenzylidene malononitrile (CS riot control agent) exposure in a U.S. Army
      basic combat training cohort.
AB  - All U.S. Army soldiers participate in mask confidence training during initial
      military training and periodically throughout their careers. Training is
      conducted by dispersing the riot control agent, o-chlorobenzylidene malononitrile
      (CS), in a relatively air-tight structure where soldiers enter and conduct a
      series of exercises that culminate with mask removal. The study described here
      quantified CS concentrations experienced by 6,723 trainees and seven chamber
      operators during U.S. Army basic combat training at Fort Jackson, South Carolina,
      from August 1 to September 25, 2012. All 6,723 trainees were potentially exposed
      to CS concentrations exceeding the American Conference of Governmental Industrial
      Hygienists threshold limit value-ceiling (TLV-C) (0.39 mg/m3), 6,589 of which
      were potentially exposed to concentrations exceeding the value deemed immediately
      dangerous to life and health (IDLH) (2.0 mg/m3) by the National Institute for
      Occupational Safety and Health. All chamber operators were exposed to
      concentrations exceeding both the TLV-C and the IDLH.

PMID- 25603651
TI  - Sensor drift and predicted calibration intervals of handheld temperature and
      relative humidity meters under residential field-use conditions.
AB  - Handheld temperature and relative humidity (T/RH) meters are commonly used in
      residential indoor air surveys. Although popular, T/RH meters are prone to sensor
      drift and consequent loss of accuracy, and thus instrument manufacturers often
      recommend annual calibration and adjustment. Field-use conditions, however, have
      been shown to accelerate electronic sensor drift in outdoor applications,
      resulting in out-of-tolerance measurements in less than one year. In the study
      described in this article, sensor drift was evaluated under residential field use
      for 30 handheld T/RH meters to predict needed calibration intervals based on
      hierarchical linear modeling. Instruments were used in 43 home visits over a 93
      day period and were calibrated (without adjustment) 49 times over the study
      period with a laboratory standard. Analysis of covariance showed significant
      drift among temperature sensors for all three instrument types (p < .0001) and
      among humidity sensors in two instruments. The authors' study suggests
      calibration frequency should be based on instrument performance under specific
      sampling conditions rather than on predetermined time intervals.

PMID- 25603652
TI  - Building environmental public health framework for chemical emergencies.

PMID- 25603653
TI  - CDC's National Environmental Public Health Tracking Network adds pesticide
      exposure and prospective climate data.

PMID- 25603654
TI  - "Situational futuring" and 44 mind-stretching scenarios to learn how to use it:
      the first 22.

PMID- 25603655
TI  - Corruption in healthcare system: an obstacle in achieving optimal outcome.

PMID- 25603656
TI  - TNF-alpha: a risk factor for ischemic stroke.
AB  - BACKGROUND: Inflammatory markers are being explored to aid in stroke diagnosis
      especially, to differentiate between clinical varieties of stroke. This study
      aimed to compare plasma tumour necrosis factor-alpha (TNF-alpha) and Interleukin
      10 (IL-10) levels between stroke patients and controls, as well as between
      hemorrhagic and ischemic varieties of stroke. METHODS: Stroke patients who were
      admitted to Shaikh Zayed Hospital Lahore and Services Hospital Lahore, Pakistan
      within 24 hours after the onset of stroke symptoms were consecutively asked to
      participate in this study from June 2011 to December 2011.Venous blood samples
      were collected within 24 hours of stroke symptoms onset. Plasma TNF-alpha levels
      and IL-10 were calculated using commercial enzyme-linked immune-sorbent assay
      (ELISA). Cytokines levels were dichotomized as detectable yes/no and were
      compared between different groups using chi square test. Continuous variables
      were compared using the student t-test. Logistic regression model was used to
      investigate the effect of various risk factors on stroke subtypes. A value of p <
      0.05 was considered significant. RESULTS: One hundred and thirty one stroke
      patients were included in the study, out of which 93 were ischemic and 38 were
      haemorrhagic stroke patients. Forty-seven healthy asymptomatic individuals were
      included .as controls Plasma TNF-alpha levels (p < 0.001, r = 0.503, CI: 18.197
      1672.950) were significantly elevated in stroke patients as compared to controls,
      along with advancing age (p = 0.002, r = 0.310, CI: 1.025-1.110) and history of
      hypertension (p = 0.002, r = 0.265, CI: 1.746-12.511). Males were found to be at
      a higher risk of developing stroke. Furthermore, history of hypertension
      (p=0.019, r= -0.294, CI: 0.134-1.500) and detectable TNF- levels (p = 0.002, r =
      0.319, CI: 2.106-23.725) were found to be significantly different between
      ischemic and haemorrhagic stroke patients. CONCLUSION: TNF-alpha level differed
      highly significantly between stroke and controls, and also between ischemic and
      haemorrhagic stroke subtypes.

PMID- 25603657
TI  - Quantitative analysis of macrophages in wound healing of rat skin subjected to
      loud noise stress.
AB  - BACKGROUND: Factors affecting skin wound healing have always been a central
      consideration in medical practice. Loud noise is biological stressor affecting
      the body systems at various levels. The present study was taken to study the
      effect of loud noise stress on the macrophages during wound healing process in
      male rat skin. METHOD: One hundred and eighty male Sprague Dawley rats were
      randomly divided into control group-A and experimental group-B. Each group
      comprised 90 animals. Control and experimental groups were further subdivided
      into three subgroups of 30 animals each, corresponding to the day of sacrifice of
      animals, i.e., day 3, 5 and 7 after surgery. After induction of local anaesthesia
      a linear full thickness incision paravertebral to thoracic spine was made on the
      dorsum of rat. The experimental group B was exposed to loud noise stimulus
      (recorded noise of aero planes and gun fire) set at 97dBA to 102 dBA with a sound
      level meter. The animals were decapitated on day 3, 5 and 7 after surgery. Tissue
      was processed for paraffin embedding and stained by Hematoxylin and Eosin and
      Mallory's trichrome stain. Data was collected for the incisional space of the
      wound. Quantitative data of number of macrophages was analysed by Student's' test
      for the detection of any significant differences between the mean number in the
      experimental and control groups. All the quantitative data was expressed as means
      +/- SE. A p-value of <= 0.05 was considered statistically significant. RESULTS:
      In this study macrophages were decreased statistically significantly at day 3
      after surgery and thereafter increased significantly on day 5 and 7 after surgery
      in the experimental subgroups as compared to their match control subgroups.
      CONCLUSION: These results show that loud noise stress affects the cells
      (macrophages) involved in the healing of the wound therefore it is expected to
      have impact on the stages of wound healing.

PMID- 25603658
TI  - Rheumatoid arthritis: the importance of evidence based diagnostic reasoning in
      preventing debilitating consequences.
AB  - BACKGROUND: The early diagnosis of Rheumatoid arthritis can improve clinical
      outcomes, in terms of morbidity and mortality. This study evaluates the role of
      evidence informed diagnostic reasoning in the early diagnosis of Rheumatoid
      arthritis. METHODS: A cross-sectional survey was conducted on 200 respondents
      inclusive of doctors and medical students, at Shifa college of Medicine,
      Islamabad from April to December 2010. A questionnaire with three common clinical
      scenarios of low, intermediate and high pre-test probability for rheumatoid
      arthritis (RA) was provided to the respondents. The differences between the
      reference and respondents' estimates of pre and post-test probability were used
      to assess the respondents' clinical diagnostic reasoning process, as a tool to
      diagnose RA early. Respondents were also enquired about the cost effectiveness or
      potential harms of Rheumatoid factor (RF). Consecutive sampling technique was
      used and the data was analysed using SPSS-15. RESULTS: In all scenarios, the pre
      test probability was estimated close to the reference estimates suggesting
      respondents' ability to rule in or rule out the disease. However, some over
      estimation of the pre-test probability was noticed in low and intermediate pre
      test probability settings. Post-test probabilities were significantly
      underestimated reflecting their inability to calculate post-test probabilities in
      all scenarios. More tests were ordered as the disease probability increased. Most
      respondents were of the opinion that RF is cost effective and safe. CONCLUSIONS:
      The significant underestimation of the post-test probability necessitates more
      emphasis on Bayesian probabilistic thinking in clinical practice to facilitate
      early diagnosis of rheumatoid arthritis.

PMID- 25603659
TI  - Stroke after coronary artery bypass surgery with and without cardiopulmonary
      bypass.
AB  - BACKGROUND: Stroke is a devastating complication of coronary artery bypass
      grafting (CABG). This study was carried out with the aim that the development of
      off pump coronary artery surgery decreases the incidence/adverse outcome due to
      extra corporeal circulation. METHODS: The data utilized in this study was
      extracted from a randomized controlled trial that was conducted from January 2006
      to March 2007 at Punjab Institute of Cardiology. One hundred patients were
      included in 'on pump' group-A, and 100 patients in 'off pump' group-B. RESULTS:
      The mean age of the patients in group-A was 53.51 +/- 9.96 years and in group-B
      it was 51.59 +/- 10.30 years. Renal failure occurred in 21% patients of group-A
      as compared to 10% of group-B while Acute Myocardial Infarction occurred in
      significantly higher number of patients in group-B (11%) as compared to group-A
      (2%). Off pump was associated with significant decrease in rate of stroke 1.5% as
      compared to on pump 3.5%. similarly there was decreased in the risk of deaths
      after stroke 0% as compared to on pump 1.5% mortality after stroke. In group A 6
      (3.5%) patients developed stroke where as in group-B 2 (1.5%) patients developed
      stroke out of these 6 patients there were 2 mortalities after stroke in group-A
      while in group-B there was no mortality after stroke within 30 days
      postoperatively. CONCLUSION: Off pump CABG is associated with significantly
      decreased rate of stroke in comparison with the on-pump CABG.

PMID- 25603660
TI  - Frequency of dentofacial asymmetries: a cross-sectional study on orthodontic
      patients.
AB  - BACKGROUND: Correction of orthodontic asymmetries is crucial to achieve
      functional occlusion, aesthetics and stability of post orthodontic treatment
      results. To date valid frequency data of dentofacial asymmetries in Pakistani
      orthodontic patients do not exist to document orthodontic treatment need. The
      objectives of this study were to determine frequency of dento-facial asymmetries,
      severity of dental asymmetries and to determine difference in frequency of
      dentofacial asymmetries in mixed and permanent dentition. METHODS: The sample of
      this cross-sectional study comprised of 280 patients (177 females and 103 males)
      with no history of previous orthodontic treatment having no craniofacial
      anomalies. Dento-facial asymmetries were assessed from pre-treatment records of
      patients. Descriptive statistics were used to determine frequency of dentofacial
      asymmetries and severity of dental asymmetries. Chi-square test was used to
      determine difference in frequency of dentofacial asymmetries in mixed and
      permanent dentition. RESULTS: Seventy eight percent (219) of patients had
      noncoincident midlines, 67.5% (189) had mandibular midline asymmetry, 43.2% (122)
      had molar asymmetry, 15.7% (44) had mandibular arch asymmetry, 14.3% (40) had
      maxillary midline asymmetry, 13.6% (38) had maxillary arch asymmetry, 6.1% (17)
      had nose deviation, and 12.1% (34) had facial asymmetry and chin deviation. In
      most patients dental midlines were deviated from one another and from facial
      midline by 1/4 lower incisor widths, while molar asymmetry was found in most
      patients by 1/4 cusp width. Mandibular arch asymmetry was more frequent in
      permanent than mixed dentition (p = 0.054). CONCLUSIONS: Non-coincident dental
      midline is most commonly seen. Nose deviation is least commonly observed.
      Mandibular arch asymmetry is more frequent in permanent than mixed dentition.

PMID- 25603661
TI  - Isolated inferior oblique myectomy for hypertropia.
AB  - BACKGROUND: Hypertropia is a condition in which one eye is elevated relative to
      the other, either intermittently or constantly. It causes significant problem
      either cosmetically or by abnormal head posture and thus needs to be corrected
      surgically. This study was conducted to evaluate the success rate and
      complications of isolated inferior oblique myectomy in patients with hypertropia.
      METHODS: Patients having hypertropia (Deviation > 6 prism diopters [PD])
      associated with inferior oblique over-action were included in this observational
      Case-series, conducted from July 2011 to December 2012, at Al Ibrahim eye
      Hospital, Karachi. Patients underwent unilateral inferior oblique myectomy. Final
      outcome was considered at the end of three months at which achievement of <= 2 PD
      of hypertropia was considered as a success. RESULTS: During the study period, 58
      patients were included. Hypertropia was most commonly associated with exotropias
      23 (39.7%) followed by esotropias in 18 (31%). Mean angle of hypertropia was
      reduced from 13.55 +/- 4.43 prism diopters to 0.48 +/- 1.08 prism diopters. Out
      of 58 patients, 55 (94.8%) had achieved success after surgery while only 3 (5.2%)
      patients had residual hypertropia of greater than 2 prism diopters (p = 0.001).
      No direct complications of procedure observed intra-operatively or up to 3 months
      post operatively but significant overcorrection of residual horizontal deviation
      observed after horizontal squint surgery in these eyes. CONCLUSION: Isolated
      inferior oblique myectomy is highly successful and safe surgical procedure for
      correction of hypertropia.

PMID- 25603662
TI  - Efficacy of vancomycin versus linezolid against coagulase-negative staphylococci
      in various clinical specimens.
AB  - BACKGROUND: Worldwide increase in antibiotic resistance has become one of the
      major problems. Optimal and rationale use of antibiotic is important to prevent
      resistance against most of the bacteria including Coagulase-negative
      Staphylococci (CoNS), which has now been recognized as an important pathogen for
      nosocomial infections. This study was carried out to determine efficacy of
      vancomycin and linezolid against CoNS in various clinical specimens. METHODS: A
      total of 2989 specimens of blood, pus and wound swab were collected from wards,
      casualty, intensive care units (ICU) and out-patient department (O.P.D), out of
      these, Staphylococci were isolated in 1017 specimens, of which 381 were
      identified as CoNS. Culture, gram stain, catalase, coagulase test and
      antimicrobial susceptibility pattern were done on these specimens according to
      clinical manual of microbiology. A total of thirteen most commonly used
      antibiotics were used in this study. Susceptibility testing was done by Kirby
      Bauer disc diffusion technique. RESULTS: Antimicrobial resistance of these
      isolates were Amoxicillin (74.8%), Amoxicillin+clavulanate (32.8%), Ciprofloxacin
      (35.2%), Ofloxacin (33.6%), Ceftriaxone (30.4%), Erythromycin (58.3%),
      Clindamycin (16.3%), Kanamycin (52.2%) Fusidic acid (41.7%), Doxycycline (24.7%),
      Vancomycin (2.6%) and Linezolid (0.8%) respectively. Isolates obtained from blood
      were 45.9%. CONCLUSION: Vancomycin showed resistance against CoNS which is a real
      threat for currently applied therapy against methicilin resistant CoNS. However,
      linezolid efficacy is higher than vancomycin against CoNS in our study, which
      suggests that this drug may be considered superior to vancomycin for the
      treatment of infections associated with CoNS.

PMID- 25603663
TI  - Efficacy and safety of subcutaneous lateral internal sphincterotomy for chronic
      anal fissure.
AB  - BACKGROUND: This study was undertaken to determine the efficacy and safety of
      subcutaneous lateral internal sphincterotomy (SLIS) for chronic anal fissure by
      assessing the relief of defecatory pain, duration of wound healing and associated
      complications such as bleeding, infection, and anal incontinence. METHODS: This
      descriptive case series was carried out at the Department of Surgery, Pakistan
      Institute of Medical Sciences (PIMS), Islamabad from September 1, 2008 to
      February 28, 2009. RESULTS: Out of fifty patients 31 were males and 19 were
      females. The mean age was 30.04 +/- 8.49 years. Defecatory pain and bleeding per
      rectum were the commonest symptoms, found among all patients. Symptomatic relief
      of pain following surgery was observed among all patients at 4th week while all
      fissures healed at 8th week. At 4th weeks follow-up visit none of the patients
      had flatus incontinence while at 8th weeks all patients had good faecal
      continence. Majority (76%) of the patients were managed as Day case or Extended
      day case surgeries. There was no in-hospital mortality in this case series.
      CONCLUSION: SLIS is a valuable surgical procedure for patients with chronic anal
      fissure. It is effective and safe, offers quick relief of defecatory pain, and
      promotes early fissure healing without being attended by any major complications.
      The initial transient incontinence of flatus and faeces improves spontaneously
      over few weeks period. Majority of the patients are manageable on day case or
      extended day case surgery basis.

PMID- 25603664
TI  - Outpatient endometrial biopsy with Pipelle vs diagnostic dilatation and
      curettage.
AB  - BACKGROUND: Pipelle is a silastic curette which does not require a tenaculum or
      straightening of the cervical fundus axis because of its flexibility and does not
      require general anaesthesia, whereas Dilatation and curettage (D&C) requires
      hospitalization and general anaesthesia along with the problem of postoperative
      pain. The objective of the study was to assess the effectiveness of Pipelle
      sampling in terms of adequate specimen collection and patients' knowledge and
      perception about Pipelle and compare it D&C. METHODS: In this randomized control
      trial, 203 women presenting with abnormal uterine bleeding were enrolled. The
      patients were randomly assigned to one of the two procedures. In group A 102
      patients were subjected to Pipelle endometrial sampling and in group B 101
      patients were enrolled for D&C. Frequencies of adequacy of histopathology reports
      and cost effectiveness of both groups were compared. Patient's knowledge,
      perception, pain and acceptability of the procedure of both groups were also
      assessed and compared. RESULTS: The mean age of the patients was 46.3 +/- 4.45
      years. Tissue obtained for histopathology was 100% adequate when the procedure
      was D&C while it was 98% in Pipelle group. In group-A 92% patients experienced no
      discomfort, with only 2% experiencing severe pain and 6% mild pain. On the other
      hand in group-B, 45% patients experienced moderate and 5% experienced severe pain
      up to 9 on visual analogue scale (VAS) postoperatively arid requiring post
      operative analgesia. The acceptability for the Pipelle suction curette was 98%
      and for the D&C group was 34%. Regarding previous knowledge of procedure none of
      patients (100%) knew about Pipelle procedure but 98% patients were aware of D&C
      procedure. Pipelle was eight times more cost effective as compared to D&C.
      CONCLUSIONS: The results of obtained by endometrial sample by Pipelle and D&C are
      compareable. Pipelle significantly produced less pain than D&C.

PMID- 25603666
TI  - Comparison of primary wound closure with delayed primary closure in perforated
      appendicitis.
AB  - BACKGROUND: Delayed primary closure in cases of acute appendicitis is debated
      among the surgeons as to whether it decreases the rate of wound infection in
      comparison to primary closure. The aim of this study was to find out the optimal
      method of wound closure in cases of perforated appendicitis. METHODS: This
      randomized control trial was conducted at the surgical units of Ayub Teaching
      Hospital Abbottabad from May to November 2012. A total of 158 patients having
      perforated appendicitis were included in the study. They were randomly divided
      two groups. The wounds were primarily closed in one group and left open with
      daily saline soaked dressing, to be closed on postoperative day 4 in case of the
      other group. The main outcome measure was wound infection. A wound was considered
      infected if it was discharging pus, was red and swollen on postoperative day 8th.
      The method of wound closure was considered efficacious if there was no wound
      infection till 8th postoperative day. RESULTS: A total of 158 patients, 56
      (35.4%) male and 102 (64.6%) female were included in the study. Primary closure
      group had a total number of 79 patients with 26 (32.9%) male and 53 (67.1%)
      female. Delayed primary group had also a total number of 79 patients with 30
      (38%) male and 49 (62%) female. The mean age of patients in the primary closure
      group was 26.67 +/- 7.32 years while in the delayed primary group was 28.15 +/-
      6.88 years. In the entire series, 36 (22.8%) patients developed wound infection.
      There was a significant association between wound infection and type of skin
      closure (Delayed Primary Closure 6.3% vs. Primary Closure 39.2%, p < 0.000).
      CONCLUSION: Delayed Primary closure is the optimal management strategy in case of
      perforated appendicitis as it decreases the incidence of wound infection.

PMID- 25603665
TI  - Frequency of albuminuria in diabetic patients presenting with macrovascular
      complications.
AB  - BACKGROUND: Diabetes mellitus is major cause of morbidity and premature mortality
      from its long-term complications such as cardiovascular disease, blindness, renal
      failure, amputation and stroke. The study was conducted to determine the
      frequency of albuminuria in diabetic patients presenting with macro-vascular
      complications like myocardial infarction (MI) and stroke. METHODS: This
      descriptive study was conducted at Ayub Medical College, Abbottabad from December
      2010 to May 2011. Total 88 diabetic patients admitted with macro-vascular disease
      were included in this study. The patients were subjected to two urine specimen's
      examination, one for routine examination for infection and dipstick analysis for
      albuminuria. Second was tested for albumin was tested in the urine. RESULTS: Out
      of 88 patients with a mean 47.12 +/- 7.58 years, 39 (44.32%) were female while 49
      (55.68%) were male. Overall albuminuria was detected in the urine of 81 out of
      total 88 patients (92%) when tested by heating method whereas it was detected in
      41 (46.6%) cases by the dipstick method. CONCLUSION: Frequency of albuminuria is
      much.higher in diabetic population with macro-vascular complications; hence
      albumin in the urine of diabetic patient can be regarded as an indicator for
      impending macro-vascular complications of diabetes.

PMID- 25603667
TI  - Financial cost to institutions on patients waiting for gall bladder disease
      surgery.
AB  - BACKGROUND: The aim of this study was to determine the financial costs to
      institution on patients waiting for gall bladder disease surgery and suggest
      measures to reduce them. METHODS: This multi-centre prospective descriptive
      survey was performed on all patients who underwent an elective cholecystectomy by
      three consultants at secondary care hospitals in Pakistan between Jan 2010 to Jan
      2012. Data was collected on demographics, the duration of mean waiting time,
      specific indications and nature of disease for including the patients in the
      waiting list, details of emergency re-admissions while awaiting surgery,
      investigations done, treatment given and expenditures incurred on them during
      these episodes. RESULTS: A total of 185 patients underwent elective open
      cholecystectomy. The indications for listing the patients for surgery were
      biliary colic in 128 patients (69%), acute cholecystitis in 43 patients (23%),
      obstructive jaundice in 8 patients (4.5%) and acute pancreatitis in 6 patients
      (3.2%). 146 (78.9%) and 39 (21.1%) of patients were listed as outdoor electives
      and indoor emergencies respectively. Of the 185 patients, 54 patients (29.2%)
      were re-admitted. Financial costs in Pakistani rupees per episode of readmission
      were 23050 per episode in total and total money spent on all readmissions was Rs.
      17,05,700/-. CONCLUSION: Financial costs on health care institutions due to
      readmissions in patients waiting for gall bladder disease surgery are high.
      Identifying patients at risk for these readmissions and offering them early
      laparoscopic cholecystectomy is very important.

PMID- 25603668
TI  - Current trends in undergraduate medical and dental research: a picture from
      Pakistan.
AB  - BACKGROUND: Initiatives taken over the last few years have led us to the day when
      most of the medical and dental institutions in the developed countries have
      established a strong research culture at undergraduate level but the situation is
      quite the contrary in Pakistan. This study was carried out to investigate the
      current trends in undergraduate medical and dental research and to highlight the
      research barriers. METHODS: A cross-sectional study was conducted at six medical
      and dental colleges of Rawalpindi and Islamabad. A structured questionnaire was
      used to collect data from 300 students. Results were recorded as percentages.
      Findings of current survey were compared with those of already reported in
      literature using chi-square test. RESULTS: Out of 300 students, 206 (68.7%)
      students had already participated in research as principal researcher, co
      researcher or as a research volunteer. Internet was most effective method of
      publicity of research opportunities reported by 74% of students. Only 36.7%
      students reported the presence of student research office at their institute.
      Accessibility to medical and dental journals and availability of research funds
      were reported by 77.2% and 13.4% of students, respectively. Lack of funding and
      academic overload were two main research barriers reported by 92.6% and 91.9% of
      students, respectively. CONCLUSION: The fraction of medical and dental students
      who are confident that they can plan, conduct and write a research study has
      increased over last four years. There is an improvement in the availability of
      research promoting activities but the number of research barriers is still high.

PMID- 25603669
TI  - Impact of body mass index on left ventricular mass.
AB  - BACKGROUND: Obesity is an independent factor implicated in left ventricular (LV)
      hypertrophy and increased left ventricular mass. Early detection of increased LV
      mass in obese patients has prognostic and therapeutic implications. METHODS: This
      case series was carried out in Choudhry Pervaiz Ellahi Institute of Cardiology,
      Multan from March to August 2011. A total of 100 consecutive patients including
      male and female referred for transthoracic echocardiography were included in this
      study. Patient's demographics were obtained using a questionnaire. Anthropometry
      (BMI) and two-dimensional echocardiography to calculate LV mass. RESULTS:
      Echocardiograms of 100 patients showing mean age 42.42 +/- 6.04 years, with BMI
      of 28.42 +/- 5.52 and LV Mass of 136.05 +/- 29.117 shown linear correlation
      between BMI and LV mass. CONCLUSION: In is concluded from the study that LV mass
      increases with increasing BMI.

PMID- 25603670
TI  - Knowledge, attitudes and practices of parents regarding antibiotic use in
      children.
AB  - BACKGROUND: Emerging resistance to antimicrobial chemotherapy is becoming a
      challenge for medicine in recent times. Un-prescribed use of antibiotics is a
      major contributor to development of this problem. In Pakistan access to
      antibiotics remains unchecked and hence results in it are over use. The aim of
      this study was to assess knowledge of parents regarding use of antibiotics, its
      associated problems, their source of information and their expectations from
      Paediatricians for prescription of anti-biotics. METHODS: This is a questionnaire
      based cross sectional study conducted in Hayatabad town, District Peshawar.
      Parents who were consenting, had children aged between 0-16 years, and were not
      related to medical profession were included in study. Total number of
      participants interviewed was 400. Analysis was done using prevalence ratios.
      RESULTS: Most of the participants were mothers. Majority of respondents were
      literate with education up till level of Graduation. 64% mentioned that they
      enjoyed a good access to healthcare. Most common source for use of antibiotics
      was Physician. 35% mentioned that antibiotics must be administered in any case of
      fever, 47% thought antibiotics to increase recovery time and 51% knew that
      antibiotics have their own side effect. The most common reason to administer un
      prescribed antibiotics was same antibiotic being prescribed by a physician
      earlier followed by family member or pharmacist recommending use of antibiotic.
      Lack of resources was denied as a reason for self-administration of antibiotics
      by majority of parents. CONCLUSION: There is a need of intervention to increase
      awareness regarding judicious use of antibiotics and to check un-prescribed
      dispensing of antibiotics.

PMID- 25603671
TI  - Lead erosion in permanent pacemaker: a cumbersome complication.
AB  - BACKGROUND: Lead erosion is one of the troublesome complications which are very
      difficult to treat and most of the time leads to device explanation and
      replacement prematurely. METHODS: From 2005 to 2011, total 415 pacemakers were
      implanted in our cardiology department at Hayatabad Medical Complex Peshawar. The
      patients were followed regularly at six month interval or more frequently in case
      there were complications. At every visit we inspected the wound site,
      electrocardiography was done and device was analyzed with compatible programmer
      for the device. If there was soreness at the site of implantation, patient was
      seen more frequently and if there was erosion of skin, wound was reopened margin
      refreshed and wound closed. Initially we closed the wound in two layers after
      reopening but we got repeated erosion with this method and so we buried the leads
      sub-muscularly as change strategy which again proved unsuccessful. Results:
      During the six years study about 415 permanent pacemakers were implanted. During
      this time period, we received: three lead erosion, which were repositioned. There
      were recurrence in two cases and they were again subjected to procedure with a
      change strategy; by burying the leads in muscles, which proved unsuccessful.
      CONCLUSION: Leads erosion can be prevented by carefully burying leads in three
      layers first in muscle followed by subcutaneous tissue and then closing the wound
      by suturing the skin during initial implantation.

PMID- 25603672
TI  - A clinical study of ectopic pregnancy.
AB  - BACKGROUND: The frequency of ectopic pregnancy is increasing throughout the globe
      and it is the most life threatening emergency in first trimester of pregnancy.
      Objective of this study was to determine the frequency, risk factors, clinical
      presentation and management of ectopic pregnancy. METHODS: This prospective
      descriptive study was conducted in Gynaecology and Obstetrical Unit-II of Liaquat
      University of Medical and Health Sciences Hospital Hyderabad from 1st May 2009 to
      30th April 2012. All women diagnosed with ectopic pregnancy were included in the
      study. A predesigned pro forma was used to record the details about demographic
      features, pre-existing risk factors, clinical features at presentation and
      management of ectopic pregnancy. Data was analysed using SPSS-11. RESULTS: Total
      numbers of admission during study period were 9600 with 60 cases of ectopic
      pregnancy, thus representing the frequency of 0.6% (1 in 160). Majority of women
      43 (72%) were of 20-30 year age, multigravida 31 (52%) were the most sufferers.
      Pelvic inflammatory disease 27 (45%), previous abortion 20 (33%), previous
      surgery 12 (20%) were seen as common risk factors; however no risk factor was
      identified in 21 (35%) women. Typical history of amenorrhea and abdominal pain
      was found in 46 (77%) women, 23 (38%) were in a state of shock. Laparotomy was
      performed in 53 (88%) women. Three (5%) women were treated successfully with
      methotrexate. Laparoscopic surgery was done in 2 patients and 2 patients were
      required both Laparoscopy proceeded by laparotomy. No maternal death related to
      ectopic pregnancy was reported in our study. CONCLUSION: The early diagnosis of
      an ectopic pregnancy is one of the greatest challenges for obstetricians. The
      importance of early diagnosis lies in the fact that the lady can be offered a
      conservative line of management which can definitely have beneficial on her
      reproductive carrier.

PMID- 25603674
TI  - Vitamin-D status at breast cancer diagnosis: correlation with social and
      environmental factors and dietary intake.
AB  - BACKGROUND: Serum levels of vitamin-D are low in breast cancer patients. Vitamin
      D levels have inverse correlations with postmenopausal state, obesity, poor sun
      exposure and low intake of vitamin-D rich diet. The objective of this study was
      to quantify levels of vitamin-D in serum to determine the degree of vitamin-D
      deficiency in breast cancer patients compared with age matched controls and to
      observe the association between serum 25-OH vitamin-D levels and personal and
      social parameters, BMI, amount of sun exposure and dietary intake. METHODS: In
      this cross-sectional analytical study all newly diagnosed breast cancer female
      patients were recruited into the study over a period of 6 months. Age matched
      healthy females were also recruited as a control group. Personal and social data
      was documented on to a pro forma. Sun exposure was determined by mid-day exposure
      to direct sunlight. Serum 25-OHD levels were studied by ELISA technique on the
      blood samples. The dietary information was collected by recall over the last 1
      year. RESULTS: Vitamin-D deficiency was found in 99% breast cancer females and
      90% in healthy females. Mean serum vitamin-D level was 9.6 +/- 5 ng/ml and 15.2
      +/- 10 ng/ml for cases and control group respectively. All breast cancer and 95%
      healthy females with BMI > 30 were found to be vitamin-D deficient. Menopausal
      state, parity, parda (veil) observation, area of living and sun exposure did not
      affect vitamin-D status in either group. Egg, fish and cheese intake revealed
      correlation with vitamin-D deficiency. Forty percent healthy females were found
      to have deficient serum vitamin-D levels despite being on supplement. CONCLUSION:
      Vitamin-D deficiency was highly prevalent among breast cancer females. Serum 25
      OHD levels exhibited an inverse correlation with high body mass index and vitamin
      D rich diet.

PMID- 25603673
TI  - Helicobacter pylori prevalence and histopathological findings in dyspeptic
      patients.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) colonizes in half of the population
      of developed and nearly all inhabitants of developing countries. The infection is
      characterized by gastritis but can present more complicated disease states. We
      intended to report prevalence of H. pylori infection by histopathology and
      presence of gastritis, activity, atrophy and intestinal metaplasia in dyspeptic
      patients of Islamabad, Pakistan. METHODS: Ninety four patients identified to be
      dyspeptic on the basis of Rome-III criteria were included in the study and
      diagnosed for H. pylori status by Histopathology. The grading and severity of
      gastritis was documented as nil, mild, moderate or severe, based on the Sydney
      system. Activity was recorded as present when an increase in the number of
      neutrophils was observed. Atrophic changes and intestinal metaplasia were also
      determined. RESULTS: Eighty three out of total 94 (88.3%) patients were positive
      for H. pylori on histopathology. Out of total 94 patients, chronic gastritis was
      observed in 89 (94.6%), evidence of activity was found in 37 (39.4%), atrophic
      changes were observed in 66 (70%) and intestinal metaplasia was present in 4
      (4.3%) patients. CONCLUSION: H. pylori infection in dyspeptic patients of
      Islamabad appears to be more related with gastritis.

PMID- 25603675
TI  - Frequency of gall bladder carcinoma in patients with acute and chronic
      cholecystitis.
AB  - BACKGROUND: Gallbladder carcinoma is a relatively uncommon neoplasm which is more
      common in the seventh decade of life compared to that of cholelithiasis which is
      in the fourth decade. The objective of the study was to determine the frequency
      of carcinoma gall bladder in cases of acute and chronic cholecystitis
      particularly with reference to cholelithiasis. METHODS: This cross-sectional
      observational study was done in the department of Surgery at Fauji Foundation
      Hospital, Rawalpindi from 1st January, 2009 till 3 1st October, 2011. All 310
      cholecystectomies performed during this period were included in this study. The
      specimens collected were macroscopically examined and sent for histopathology.
      All the reports were reviewed and the results recorded. RESULTS: Out of 310
      cases, 27 (8.7%) had acute cholecystitis and 280 (91.2%) were chronic
      cholecystitis. 3 specimens got autolysed and therefore excluded from the study.
      290 cases had cholelithiasis. 2 out of 290 calculous cases were found to have
      coexistent carcinoma gall bladder proven on histopathology. CONCLUSION: Frequency
      of carcinoma gallbladder associated with cholelithiasis discovered incidentally
      after cholecystectomy is very low in our patients.

PMID- 25603676
TI  - Prevalence of the metabolic syndrome and its component abnormalities among school
      age Pakistani children.
AB  - BACKGROUND: Concurrence of central adiposity, hypertension, hyperglycaemia, and
      atherogenic dyslipidaemia has been termed as the metabolic syndrome. High
      prevalence of the syndrome has been reported globally over the last decade.
      METHODS: This cross-sectional study is based on a sample of eighty five children,
      ranging in age from six to twelve years. After parental consent, height, weight,
      waist circumference,, and blood pressure were measured and investigation requests
      for fasting plasma glucose and fasting lipid profile were given. Children with
      known metabolic disorders, and those using metabolic-profile-altering medication
      were excluded. RESULTS: The prevalence of metabolic syndrome, according to the
      various definitions, varied from as high as 16.5% (95% CI: 9.3-26.1%) to as low
      as 1.8% (95% CI: 0.03-6.4%). The most prevalent of the component abnormalities
      was blood pressure above 90th percentile, positive in 54% (95% CI: 43.0-65.0).
      HDL-c was low (<=1.3 mmol/L) in 36.5% (95% I: 26.3-47.6%), and waist
      circumference high (>75th percentile) in 30.6% (95% CI: 21.0-41.5%). Both
      systolic blood pressure and triglycerides to HDL-cholesterol ratio showed a
      linear trend of increasing with increasing quartiles of waist and body mass index
      (BMI). CONCLUSION: Depending on the cut-off values used for defining the
      component abnormalities, the metabolic syndrome may be quite prevalent in this
      population. Waist circumference above 75th percentile and even a single reading
      of blood pressure above 90th percentile should be considered a warning sign,
      indicating further investigation and lifestyle interventions.

PMID- 25603677
TI  - Variation in lung volumes and capacities among young males in relation to height.
AB  - BACKGROUND: Vital Capacity (VC) is defined as a change in volume of lung after
      maximal inspiration followed by maximal expiration is called Vital Capacity of
      lungs. It is the sum of tidal volume, inspiratory reserve volume .and expiratory
      reserve volume. Vital capacity of normal adults ranges between 3 to 5 litres. A
      number of physiological factors like age, gender, height and ethnicity effect
      lung volumes. The reference values of lung volume and capacities were calculated
      previously and those studies played pivotal role in establishing the fact that
      air volume capacities measured in an individual fall within a wide range among
      healthy persons of same age, gender and height buit with different ethnicity. The
      objective of this study was to evaluate the changes in vital capacity in with
      height and gender. METHODS: This cross-sectional study included 74 male students
      in the Department of Physiology, Liaquat University of Medical and Health
      Sciences, Jamshoro during January-March, 2014. The volunteers were divided into 2
      groups of height <= 167.4 cm and > 167.4 cm. The volunteers' height was measured
      in cm. Vital capacity of the subjects was measured using standard protocol. Mean
      +/- SD of age, height and vital capacity were calculated. RESULTS: Mean vital
      capacity in students with height > 167.4 cm was higher than average vital
      capacity of students with height <= 167.4 cm. It might be due to the increased
      surface area of the lungs in relation with increasing height. CONCLUSIONS: There
      are variations in vital capacity of individuals in relation to their heights,
      within the same ethnic and age groups.

PMID- 25603678
TI  - Association between psoriasis and coeliac disease related antibodies.
AB  - BACKGROUND: Psoriasis is a common, chronic, disfiguring, inflammatory and
      proliferative condition of skin manifested by red, scaly, sharply demarcated,
      indurated plaques present particularly over the extensor surfaces and scalp. The
      disease has been found to be associated with celiac disease related antibodies
      with variable frequencies in different populations of the world. The subset of
      patients showing this association have a higher psoriasis severity and also
      respond well to cost effective way of gluten free diet. There is a need to work
      out the frequency of these antibodies in our local psoriatic patients. METHODS:
      The study was carried out in Department of Dermatology, Military Hospital
      Rawalpindi from 4th June to 4th December, 2008. A total of 80 patients of both
      gender, aged more than 15 with a clinical diagnosis of psoriasis attending
      dermatology outpatient department were selected. Relevant history and thorough
      physical examination was performed and disease characteristics like previous
      treatments received and history of arthropathy were obtained. Coeliac disease
      related antibodies were assessed on serum by indirect immunofluorescence and data
      was analysed using software SPSS-13. RESULTS: From the study of 80 patients,
      celiac disease related antibodies were found in none of the cases. All the severe
      and mild to moderate patients of psoriasis were negative for IgA antigliadin
      antibodies, IgG antigliadin antibodies and IgA anti-reticulin antibody.
      CONCLUSION: This study concludes that celiac disease related antibodies are not
      present in psoriatic patients irrespective of severity of disease in our local
      population.

PMID- 25603679
TI  - Morphometrical analysis of intervillous space and villous membrane thickness in
      maternal anaemia.
AB  - BACKGROUND: Anaemia in pregnancy is linked with an increased risk of preterm
      delivery, low birth weight, perinatal and maternal mortality and it is related
      with variable histo-morphological changes in placenta which show a reflection for
      the poor foetal outcome. The objective of this study is to assess the micro
      morphometery of intervillous space and villous membrane of placenta in anaemic
      mothers. METHODS: This case control study was carried out at Army Medical
      College, National University of Sciences and Technology Islamabad in
      collaboration with Department of Obstetrics and Gynaecology, Military Hospital,
      Rawalpindi, Pakistan, from December 2011 to November 2012. A total of 75
      placentas were included, that were divided into study and control group. In
      control group (n = 15) placentas were taken from mothers having normal
      haemoglobin levels and study group (n = 60) included placentas from anaemic
      mothers having haemoglobin less than 11g/dl. Study group was subdivided into
      three groups, i.e., mildly (10.0-10.9 g/dl), moderately (7.0-9.9 g/dl) and
      severely (< 7 g/dl) anaemic group. Three representative sections were taken from
      placenta, i.e., one close to umbilical cord (A), one from periphery (C) and one
      midway between A and C (B).Ocular micro-meter was used to measure intervillous
      space and villous membrane thickness. RESULTS: Intervillous space was prominent
      in study groups (41.26 +/- 16.33 im) as compared to control group (15.98 +/- 3.81
      im) (p < 0.05). Thickness of villous membrane was significantly less in study
      group as compared to control group (2.97 +/- 0.70) (p < 0.05). CONCLUSION: The
      present study showed wide intervillous space and thin villous membrane in study
      group as compared to control group reflecting adaptive changes in response to
      hypoxiain maternal anaemia.

PMID- 25603680
TI  - Treatment of chronic hepatitis-C with standard interferon and ribavirin.
AB  - BACKGROUND: The prevalence of hepatitis-C is on the rise in Pakistan. Treatment
      of chronic hepatitis-C with pegylated interferon is expensive as compared to
      standard interferon. The objective of the study was to find out the end treatment
      response rate with standard interferon and ribavirin. METHODOLOGy: This case
      series study was conducted in Ayub Teaching Hospital Abbottabad.and Orush General
      Hospital over a period of two years. 170 patients were included in the study.
      These patients were HCV PCR positive either by qualitative or quantitative assay,
      had no other comorbidity or decompensated disease. The treatment started with
      standard interferon and ribavirin for six months. After the six months at the end
      of treatment again HCV PCR assay was done to detect hepatitis-C virus in the
      blood. Those who were PCR negative were responders and positive are non
      responder. RESULTS: The cumulative response rate was 73.5%, both sexes responded
      equally. Patients below 30 years had the highest response rate and similarly
      patients having normal liver had better response than those having any degree of
      fibrosis. Baseline haemoglobin and ALT level did not have significant effect on
      treatment. CONCLUSION: Standard interferon is equally effective and comparable
      with the pegylated interferon which is costly and out of reach of many patients.
      It is therefore recommended, that combination of standard interferon and
      ribavirin may be the first line of treatment for chronic hepatitis-C treatment in
      Pakistan and pegylated interferon may be reserved for non-responders or relapsed
      cases.

PMID- 25603681
TI  - Endoscopic findings in patients presenting with oesophageal dysphagia.
AB  - BACKGROUND: Dysphagia is the difficulty in swallowing and is often described by
      the patients as a 'perception' that there is an impediment to the normal passage
      of the swallowed material. It is frequently observed that there is an association
      of dysphagia with serious underlying disorders and warrants early evaluation. The
      current study aimed to determine the frequency of common endoscopic findings in
      patients presenting with oesophageal dysphagia. METHODS: This cross-sectional
      descriptive study was carried out in the department of Gastroenterology, Ayub
      Medical College, Abbottabad, from October 2012 to April 2013. Consecutive
      patients with dysphagia were included in the study and were subjected to
      endoscopy. RESULTS: A total of 139 patients presenting with dysphagia were
      studied, 81 (58.3%) were males and 58 (41.7%) were females. The mean age was
      52.41 +/- 16.42. Malignant oesophageal stricture was the most common finding
      noted in 38 (27.3%) patients with 28 (73.7%) males and 23 (60.5%) patients among
      them were above the age of 50 years. It was followed by normal upper
      Gastrointestinal (GI) endoscopy in 29 (20.9%) patients and reflux esophagitis in
      25 (18.0%) patients. Schatzki's ring was present in 14 (10.1%) patients; benign
      oesophageal strictures in 12 (8.6%) patients while achalasia was noted in 7
      (5.0%) patients. 14(10.1%) patients had findings other than the ones mentioned
      above. CONCLUSION: Malignancies are a more common cause of dysphagia in our
      population and early diagnosis can result in proper treatment of many of these
      cases.

PMID- 25603682
TI  - Comparison of perinatal outcome in growth restricted fetuses retaining normal
      umbilical artery Doppler flow to those with diminished end-diastolic flow.
AB  - BACKGROUND: Intrauterine growth restriction /retardation (IUGR) is defined as
      birth weight below the 10th percentile for a given gestational age. Placental
      insufficiency is the primary cause of intrauterine growth retardation in normally
      formed fetuses and can be identified using umbilical artery Doppler velocimetry
      which is a non-invasive technique. The objective of this study was to compare
      perinatal outcome in growth restricted fetuses retaining normal umbilical artery
      Doppler flow to those with diminished or severely reduced/absent end-diastolic
      flow. METHODS: This cross sectional study was conducted at Radiology department
      of Pakistan Navy Ship (PNS) Shifa Hospital, Karachi over one year period from.
      Established cases of asymmetrical IUGR, having estimated fetal weight < 10th
      percentile for gestational age and between 28-40 weeks of gestation were included
      in the study. Pulsatility index (PI) was calculated for each case. Perinatal
      outcomes like early delivery, caesarean section, respiratory distress syndrome,
      necrotizing enterocolitis, admission to neonatal ICU, prenatal and neonatal death
      were evaluated. Chi-square test was used to compare proportion difference of
      perinatal outcomes for normal and abnormal umbilical artery velocimetry, with
      0.05 level of significance. RESULTS: Umbilical artery Doppler velocimetry showed
      a significant correlation with the perinatal outcome. In 90% of cases of IUGR
      having abnormal waveform, poor perinatal outcome was seen as compared to only
      33.3% retaining normal Doppler flow. CONCLUSION: Growth restricted fetuses with
      normal umbilical artery Doppler velocimetry were at lower risk than those with
      abnormal waveforms.

PMID- 25603683
TI  - Laparoscopic cholecystectomy: experience at a tertiary level hospital.
AB  - BACKGROUND: Cholecystectomy is the most frequently performed abdominal operation
      and currently laparoscopic cholecystectomy (LC) is considered gold standard being
      performed in 90% cases of symptomatic gallstones in USA since 1992. The aim of
      the study was to determine results obtained with LC at our setup. METHODS: This
      observational case series study was conducted in department of General Surgery,
      Combined Military Hospital, Rawalpindi, from August 2009 to August 2011. The
      study participants were patients of both gender aged 14-75 years undergoing LC.
      Surgery was performed by consultant as well as resident surgeon. Demographic
      variables, intraoperative findings, mean operation time, hospital stay,
      conversion rate, morbidity and mortality were evaluated. Factors influencing rate
      of conversion were also studied. RESULTS: A total of 504 patients were included.
      Mean age was 42.64 years (range 14-75 years) with a female: male ratio of
      3.9:1.2. Comorbidities were found in 36.7% patients. Main indication of surgery
      was symptomatic cholelithiasis (78.57%). Mean operative time was 40.1 +/- 6.9
      minutes which increased to 75.12 +/- 8.9 minutes in converted cases (p-value
      .000). Mean hospital stay was 1.89 +/- 1.1 days that significantly increased in
      converted cases (5.7 +/- 1.6 days) (p-value .000). Major surgical complications
      occurred in 3.17% patients. Common bile duct injury (CBDI) was found in 04 cases
      (0.79%). Conversion to laparotomy was required in 3.97% cases. Factors that
      influenced the rate of conversion included: age > 60 years, acute cholecystitis,
      coexisting diseases, ASA grade III/IV and inexperienced surgeon (p-value .000).
      Total complication rate was 3.56%, morbidity being 3.17% and mortality 0.39%.
      CONCLUSION: Laparoscopic cholecystectomy offers shorter hospital stay and low
      morbidity/mortality. The operative time is short and procedure is standard, safe
      and effective method both for uncomplicated and complicated cholelithiasis.

PMID- 25603684
TI  - Problems of group dynamics in problem based learning sessions.
AB  - BACKGROUND: Beneficial effects of Problem Based Learning (PBL) in medical
      education are often emphasized. However, there is another side of the coin. This
      study was conducted to find out frequency of PBL group problems in our setup and
      the influence of these problems on students' learning. We also compared the
      perception of students and tutors as regard to frequency and level of hindrance
      caused by these problems in PBL sessions. METHODS: This cross sectional study was
      conducted at Foundation University Medical College, Islamabad. 100 students of
      3rd year MBBS of 2011 and their 17 PBL tutors were asked to fill a questionnaire.
      They were asked to rank the factors according to frequency (perceived frequency)
      and according to the level of hindrance to learning these factors are causing.
      All data was entered and analysed using SPSS-12. RESULTS: Students ranked
      "Dominant student" as the most important problem and. "Psychosocial factors" as
      the least important problem. Tutors ranked "Quiet student" as the-most important
      problem and "Personality clash" as the least important factor. Student's ranked
      "Dominant student" as the problem causes most hindrance and "Quiet student" as
      the problem causing least hindrance. Tutors ranked "Lack of commitment" as the
      problem causing most hindrance and "Personality clash" as the problem causing
      least hindrance. There was good agreement between the students and the tutors on
      all the factors regarding important problem except "Lateness, absenteeism" (p =
      0.04) and "Personality clash" (p = 0.001). Similarly there was good agreement
      between the students and the tutors on all the factors regarding hindrance except
      "Lack of commitment" (p = 0.015) and "Personality clash" (p = 0.023). CONCLUSION:
      The present study showed that from both students' and tutors' perspectives, the
      ranking of most important problems that can disturb PBL session function and the
      level of hindrance they cause were statistically similar for majority of the
      problems.

PMID- 25603685
TI  - Frequency of modifiable risk factors in stroke patients.
AB  - BACKGROUND: Stroke is one of the common causes of admission in medical and
      neurology units in hospitals. The aim of this study was to find out the frequency
      of modifiable risk factors, and association of ischaemic stroke with these risk
      factors in stroke patients admitted in Ayub Teaching Hospital Abbottabad.
      METHODS: This a cross-sectional descriptive hospital based study, carried out in
      medical units of Ayub Teaching Hospital, Abbottabad on 150 patients with stroke.
      Thorough history, clinical examination and appropriate investigations were
      performed to collect all the relevant information. CT scan was done to confirm
      the diagnosis. RESULTS: Out of 150 subjects, 90 (60%) were males, while 60 (40%)
      were females. Ischaemic stroke was found in 105 (70%) patients and 45 (30%) were
      having haemorrhagic stroke. The risk factors were hypertension in 127 (84.7%),
      diabetes 31 (20.7%), Coronary artery diseases 31 (20.7%), previous TIA/stroke 42
      (28%), smoking 28 (16.7%) and obesity 16 (10.7%). CONCLUSION: There was no
      statistically significant association between risk factors and type of stroke
      except coronary artery diseases.

PMID- 25603686
TI  - Functional status of vascular endothelium in diabetes mellitus.
AB  - Normal endothelial cells synthesize and release biologically active substances.
      These substances maintain homeostasis through adequate blood flow, delivery of
      nutrients, activation and inhibition of coagulation proteins, prevention of
      thrombosis and diapedesis of leukocyte. Endothelial dysfunction implies failure
      of vascular endothelium to perform its normal functions of vasodilatation and
      vasoconstriction. It results from an imbalance between endothelium derived
      constricting and relaxing factors. Altered endothelial cell activity predisposes
      to increased production of vasoconstrictors, i.e., prostaglandins, endothelins,
      glycated proteins, endothelial adhesion molecules and platelet and vascular
      growth factors. These changes enhance vasomotor tone, vascular permeability,
      growth and remodeling of the vessels. Diabetes is associated with abnormalities
      of vascular endothelium. Several regulatory vasodilators and vasoconstrictors are
      altered in diabetes leading to diabetic vascular complications. Balance between
      dilating and constricting substances is altered and is shifted towards
      vasoconstriction in diabetes. Disturbances in the endothelial functions lead to
      increased platelet adhesion and aggregation in patients with diabetes. Activated
      platelets interact with endothelial cells and leukocytes in the genesis of
      atherosclerosis. High level of Von Willebrand factor (vWF) is a consistent
      finding in diabetes. Increased vWF level is one of the major risk factors for the
      development of micro vascular complications. High levels of vWF may predict
      cardiovascular disease progression in diabetes mellitus.

PMID- 25603688
TI  - Impact of prosthodontic treatment on the oral health related quality of life in a
      maxillectomy patient with multiple impairments.
AB  - Oral Health Related Quality of Life is an important component in the treatment of
      a patient. Patients with multiple impairments have a compromised quality of life,
      which is further worsened by ablative maxillary surgery. A properly made oral
      prosthesis aids in the daily life functions and therefore, has a positive impact
      on the quality of life of the patient. This article discusses a case in which
      prosthodontic treatment improved the Oral Health Related Quality of Life in a
      maxillectomy patient having multiple impairments.

PMID- 25603687
TI  - Giant ovarian cyst--an unusual finding.
AB  - A 16 year old unmarried girl presented with complaints of abdominal distension,
      vomiting, constipation, difficulty in breathing and restlessness. On examination
      abdomen was grossly distended with fluid thrill. Ultrasonographic examination
      revealed that there was a huge cystic collection with internal debris, multiple
      septations involving the whole abdomen and pelvis originating from right ovary.
      The left ovary was normal. Her laparatomy was done. A giant ovarian cyst
      measuring 45 x 32 x 28 cm, which weighed 18 Kg (almost 1/3 of whole body weight),
      was removed as such like a yoyo balloon. Post-operative recovery was smooth.
      Histopathological examination revealed that it was mucinous cystadenoma.

PMID- 25603689
TI  - Fibroma of the tendon sheath--a rare hand tumor following repetitive trauma to
      the palm.
AB  - Fibroma of the tendon sheath (FTS) is a rare, benign, soft tissue lesion.
      Clinically, FTS presents similarly to the more common giant cell tumour of the
      tendon sheath. It can be distinguished histologically by the lack of giant cells,
      foamy histiocytes and synovial cells. The author presents a case of FTS involving
      the flexor tendon to the fourth metacarpal following repetitive trauma. A 42 year
      old man presented with a three year history of painless mass in the right palm
      that had increased in size and became painful recently. Examination demonstrated
      6 x 4 cm firm, nodular, superficial mass that was adherent to the underlying
      structures. Radiographs revealed soft tissue mass. Ultrasound showed a solid
      heterogeneous mass and the MRI demonstrated that the mass cantered predominantly
      at the mid and distal portion of fourth metacarpal. Fine Needle Aspiration
      Cytology was inconclusive. The patient underwent excisional biopsy of the lesion
      showing lobulated lesion closely resembling hyalinized collagen. Neither vascular
      proliferations, necrosis, nor mitoses were observed. A diagnosis of FTS was made.
      The case report provided an additional rare case to literature of a FTS and
      highlights the need to consider this entity in the differential diagnosis of any
      soft tissue lesion in the hand after repetitive trauma. Two months later the
      patient demonstrated full range of movements in the hand.

PMID- 25603690
TI  - Role of isotretinoin in cancer prevention and management in malignancies
      associated with xeroderma pigmentosum.
AB  - We report a case of 15 year old female patient of xeroderma pigmentosum with
      large squamous cell carcinoma on the left side of cheek. She received combination
      chemotherapy with isotretinoin for a period of 4 months and showed complete
      clinical remission of tumour. The role of isotretinoin in cancer prevention and
      management of malignancies associated in xeroderma pigmentosum is also reviewed
      through literature.

PMID- 25603691
TI  - Ureteral triplication and contralateral duplication with vesicoureteral reflux.
AB  - Ureteral triplication is a rare congenital anomaly of the urinary tract. Since
      the first description by Warny in 1870, approximately 100 known cases have been
      reported in the literature, often accompanied by a variety of associated
      anomalies in contralateral kidney. This report presents a case of ureteral
      triplication with contralateral duplication and vesicoureteral reflux (VUR) of
      the upper moiety on the triplicate side. The patient was a 10 year old male who
      presented with a history of recurrent urinary tract infections and right loin
      pain. ACT urogram was performed which showed a triplicate right ureter with gross
      hydroureter of the upper moiety. There was a duplex system present on the left
      side. The patient underwent right upper pole heminephroureterectomy.

PMID- 25603692
TI  - Controversies in the use of fresh frozen plasma in critically ill small animal
      patients.
AB  - OBJECTIVE: To review the literature supporting or discouraging the use of fresh
      frozen plasma (FFP) transfusion in critically ill patients. DATA SOURCES: Human
      and animal publications were searched using PubMed without time limits and the
      following keywords were used: "fresh frozen plasma," "coagulopathy,"
      "hypocoagulable state," "hypercoagulable states," and "critical illness." HUMAN
      DATA SYNTHESIS: The commonly used tests of coagulation (eg, prothrombin time,
      activated partial thromboplastin time, international normalized ratio) are poorly
      predictive of clinical bleeding. FFP use in critically ill patients is unlikely
      to result in improved outcomes and may be associated with increased risks.
      VETERINARY DATA SYNTHESIS: There is insufficient evidence to make definitive
      conclusions regarding the use of FFP in critically ill animals, but clinical
      studies are underway that may provide further data that clarify the optimal use
      of FFP in animals. CONCLUSIONS: The use of FFP in critically ill patients remains
      controversial. In the absence of clinical bleeding or a risk for clinical
      bleeding associated with a planned procedure, treatment use of FFP is not
      recommended in human patients. There are insufficient data in critically ill
      animals to enable formulation of recommendations. Further research is warranted
      in dogs and cats to establish evidence-based guidelines.

PMID- 25603693
TI  - Identification and effect of two flavonoids from root bark of Morus alba against
      Ichthyophthirius multifiliis in grass carp.
AB  - Ichthyophthirius multifiliis (Ich) is an important ciliate that parasitizes gills
      and skin of freshwater fish and causes massive fish mortality. In this study, two
      flavonoids (kuwanons G and O) with anti-Ich activity were isolated by bioassay
      guided fractionation from the root bark of Morus alba, an important plant for
      sericulture. The chemical structures of kuwanons G and O were elucidated by
      spectroscopic analyses. Kuwanons G and O caused 100% mortality of I. multifiliis
      theronts at the concentration of 2 mg/L and possessed a median effective
      concentration (EC50) of 0.8 +/- 0.04 mg/L against the theronts. In addition,
      kuwanons G and O significantly reduced the infectivity of I. multifiliis theronts
      at concentrations of 0.125, 0.25, 0.5, and 1 mg/L. The median lethal
      concentrations (LC50) of kuwanons G and O to grass carp were 38.0 +/- 0.82 and
      26.9 +/- 0.51 mg/L, which were approximately 50 and 35 times the EC50 for killing
      theronts. The results indicate that kuwanons G and O have the potential to become
      safe and effective drugs to control ichthyophthiriasis.

PMID- 25603694
TI  - Adverse event reporting in studies of penetrating acupuncture during pregnancy: a
      systematic review.
AB  - BACKGROUND: Acupuncture within pregnancy has frequently been investigated, often
      finding this to be more effective than standard care. However, the adverse event
      severity, types and occurrence are unclear. OBJECTIVE: To investigate the quality
      of reporting adverse events and to attempt to identify occurrence, type and
      severity of adverse events in acupuncture and non-acupuncture groups. DATA
      SOURCES: MEDLINE, CINAHL, Allied and Complementary Medicine Database, and
      Physiotherapy Evidence Database (PEDro) were searched for relevant studies
      between 2000 and 2014. STUDY SELECTION: Seventeen studies using penetrating
      acupuncture and making comment on adverse events experienced were included.
      Quality appraisal of the selected publications was performed using either the
      PEDro scale or the Downs and Black checklist. Quality of reporting was evaluated
      against STRICTA and CONSORT guidelines, with data on adverse events extracted in
      accordance with CONSORT and Good Clinical Practice adverse event guidelines.
      RESULTS: Overall quality of reporting of adverse events was poor, with
      information describing the adverse events often lacking in detail. A number of
      trends were noted: adverse events occurring within a treatment session was 3-17%
      in the acupuncture groups and 4-25% in the non-acupuncture groups. The percentage
      of women affected by an adverse event was between 14 and 17% in the acupuncture
      groups and between 15 and 19% in non-acupuncture groups. CONCLUSIONS: Adverse
      event reporting within acupuncture trials is generally poor. The trends noted
      were that adverse events do occur, but would appear to be largely minor and
      comparable to non-acupuncture-related interventions.

PMID- 25603695
TI  - Endovascular approach to acute hemorrhage in locally advanced breast cancer.
AB  - We report a case of a woman with recurrent axillary fungating breast cancer who
      developed catastrophic hemorrhage from tumor erosion of her axillary artery. This
      was treated successfully with endovascular placement of a covered arterial stent.
      We discuss the suitability of endovascular therapy for patients with advanced
      malignancy given its lower morbidity in this population with decreased life
      expectancy. 

PMID- 25603696
TI  - Poorer functionality is related to better quality of life response following the
      use of biological drugs: 6-month outcomes in a prospective cohort from the Public
      Health System (Sistema Unico de Saude), Minas Gerais, Brazil.
AB  - We aim to analyze factors associated with the quality of life (QOL) response of
      individuals with rheumatic diseases treated by the Public Health System (Sistema
      Unico de Saude) with biological disease-modifying antirheumatic drugs (bDMARDs).
      Data from 428 patients using bDMARDs were collected using a standardized form at
      baseline and 6 months after the onset of treatment. The average reduction of the
      scores on EuroQol-five dimension was 0.11 +/- 0.18 6 months after the onset of
      treatment with bDMARDs, denoting significant improvement of the participants'
      QOL. All the investigated types of disease exhibited significant improvement at
      the 6-month assessment, without any difference among them (p = 0.965). The
      participants with baseline poorest functionality and best QOL exhibited the best
      QOL outcomes after 6 months of treatment. Our study showed that the use of
      biological drugs induced considerable improvement in the participants' QOL. 

PMID- 25603698
TI  - Tools, insights and feedback.

PMID- 25603697
TI  - A mediation approach to understanding socio-economic inequalities in maternal
      health-seeking behaviours in Egypt.
AB  - BACKGROUND: The levels and origins of socio-economic inequalities in health
      seeking behaviours in Egypt are poorly understood. This paper assesses the levels
      of health-seeking behaviours related to maternal care (antenatal care [ANC] and
      facility delivery) and their accumulation during pregnancy and childbirth.
      Secondly, it explores the mechanisms underlying the association between socio
      economic position (SEP) and maternal health-seeking behaviours. Thirdly, it
      examines the effectiveness of targeting of free public ANC and delivery care.
      METHODS: Data from the 2008 Demographic and Health Survey were used to capture
      two latent constructs of SEP: individual socio-cultural capital and household
      level economic capital. These variables were entered into an adjusted mediation
      model, predicting twelve dimensions of maternal health-seeking; including any
      ANC, private ANC, first ANC visit in first trimester, regular ANC (four or more
      visits during pregnancy), facility delivery, and private delivery. ANC and
      delivery care costs were examined separately by provider type (public or
      private). RESULTS: While 74.2% of women with a birth in the 5-year recall period
      obtained any ANC and 72.4% delivered in a facility, only 48.8% obtained the
      complete maternal care package (timely and regular facility-based ANC as well as
      facility delivery) for their most recent live birth. Both socio-cultural capital
      and economic capital were independently positively associated with receiving any
      ANC and delivering in a facility. The strongest direct effect of socio-cultural
      capital was seen in models predicting private provider use of both ANC and
      delivery. Despite substantial proportions of women using public providers
      reporting receipt of free care (ANC: 38%, delivery: 24%), this free-of-charge
      public care was not effectively targeted to women with lowest economic resources.
      CONCLUSIONS: Socio-cultural capital is the primary mechanism leading to
      inequalities in maternal health-seeking in Egypt. Future studies should therefore
      examine the objective and perceived quality of care from different types of
      providers. Improvements in the targeting of free public care could help reduce
      the existing SEP-based inequalities in maternal care coverage in the short term.

PMID- 25603699
TI  - Feedback: ensuring that it leads to enhanced learning.

PMID- 25603700
TI  - Comparing general practice and hospital rotations.
AB  - BACKGROUND: The Prevocational General Practice Placement programme (PGPPP) aims
      to provide junior doctors with professional, well-supervised, educational
      rotations in general practice. There is a paucity of literature evaluating the
      educational effectiveness of the PGPPP. This study aims to compare general
      practice rotations with hospital rotations, with respect to teaching and support,
      acquisition of skills and knowledge, and role autonomy. METHODS: All junior
      doctors who participated in a PGPPP rotation were invited to complete a voluntary
      anonymous online survey using the Postgraduate Hospital Educational Environment
      Measure (PHEEM) inventory. The PHEEM presents Likert scales grouped into four
      subscales for participants to rate statements about their rotations. Surveys were
      completed at the end of the year in which doctors undertook a PGPPP rotation, and
      covered all rotations. These survey findings were used to compare general
      practice and hospital rotations. RESULTS: In all four subscales of teaching,
      clinical skills, social support and role autonomy, the general practice rotation
      performed as well as, or better than, hospital rotations in the areas of
      emergency, medicine, and surgery. General practice outperformed all other
      rotations in 15 out of 20 statements across all subscales. DISCUSSION: This study
      demonstrates the educational value of a general practice placement in comparison
      with hospital placements. Expansion of the PGPPP should be considered to provide
      all junior doctors with the benefits of exposure to generalist skills in the
      community.

PMID- 25603701
TI  - Changes in teaching delivery by foundation doctors.
AB  - BACKGROUND: Contributing to the education of students as a junior doctor, with a
      busy rota, in an ever-evolving health care system can be challenging. METHODS: A
      4-month timetable was organised to fit in with both the commitments of 60
      foundation doctors and 120 final-year medical students. Using the already
      established online undergraduate timetable system, foundation doctors created
      regular sign-up teaching sessions for students to attend. Foundation doctors had
      their teaching assessed by senior colleagues, enabling work-based assessments to
      be completed and mapped to their curriculum. Feedback from both students and
      foundation doctors was collected using free-text answers and scale ratings.
      RESULTS: A total of 49 foundation doctors and 70 medical students were involved
      in the pilot teaching scheme. Using thematic analysis from the feedback, 76 per
      cent of foundation doctors reported an increased confidence in delivering
      teaching. In relation to the students, 75 per cent attended regular teaching
      sessions, 80 per cent found the teaching sessions relevant to their learning and
      preparation for final examinations, and 97 per cent would recommend this scheme
      to the next cohort of students. DISCUSSION: Teaching hospitals should encourage
      regular undergraduate teaching led by foundation trainees. Incorporating a
      flexible timetable and ensuring teacher availability can allow the delivery of
      high-quality teaching that is not only beneficial for the student but also for
      junior doctors keen to enhance their teaching ability. By being involved in
      regular teaching, junior doctors are able to build the skills, attitudes and
      practices of being competent clinical teachers, thereby preparing them to become
      the educators and trainers of the future.

PMID- 25603702
TI  - Innovative health systems projects.
AB  - BACKGROUND: Residency programmes struggle with the systems-based practice and
      improvement competency promoted by the Accreditation Council for Graduate Medical
      Education. The development of Innovative Health Systems Projects (IHelP) was
      driven by the need for better systems-based initiatives at an institutional
      level. Our objective was to develop a novel approach that successfully
      incorporates systems-based practice in our Graduate Medical Education (GME)
      programmes, while tracking our impact on health care delivery as an academic
      medical centre. METHODS: We started the IHelP programme as a 'volunteer
      initiative' in 2010. A detailed description of the definition, development and
      implementation of the IHelP programme, along with our experience of the first
      year, is described. Residents, fellows and faculty mentors all played an
      important role in establishing the foundation of this initiative. Following the
      positive response, we have now incorporated IHelP into all curricula as a
      graduating requirement. IHelP has promoted scholarly activity and faculty
      mentorship, [and] has improved aspects of patient care and safety RESULTS: A
      total of 123 residents and fellows, representing 26 specialties, participated. We
      reviewed 145 projects that addressed topics ranging from administrative and
      departmental improvements to clinical care algorithms. The projects by area of
      focus were: patient care - clinical care, 38 per cent; patient care - quality, 27
      per cent; resident education, 21 per cent; and a cumulative 16 per cent among
      pharmacy, department activities, patient education, medical records and clinical
      facility. DISCUSSION: We are pleased with the results of our first year of
      incorporating a systems-based improvement programme into the GME programmes. This
      initiative has promoted scholarly activity and faculty mentorship, has improved
      aspects of patient care and safety, and has led to the development of many
      practical innovations.

PMID- 25603703
TI  - Departmental induction and the simulated surgical ward round.
AB  - BACKGROUND: Departmental induction for junior doctors is a very important part of
      the process of handover, so as to facilitate continuity of care and patient
      safety. Historically this is led by senior doctors within the department, and may
      not cover the topics that are most needed. CONTEXT: An audit of induction of our
      junior doctors highlighted concerns, including inadequate training on surgical
      ward rounds and preparedness for their role. Consultant feedback suggested ward
      rounds were often of poor quality, causing delays, potentially affecting patient
      care and limiting the time for teaching. INNOVATION: A new near-peer induction
      including simulated ward rounds was introduced. An updated written survival guide
      was also developed. The induction included a presentation of common cases. The
      simulated ward round included the use of a high-fidelity simulation suite to
      allow realistic scenarios. Results demonstrated an improvement in the perceived
      preparedness of junior doctors for their role within the department. Overall
      preparedness improved from 5.80/10 to 8.75/10 (0, not prepared at all; 10, fully
      prepared for all day-to-day tasks). Overall satisfaction at the end of the
      placement was high, with all juniors recommending the placement. Consultant
      feedback demonstrated an 83 per cent improvement in their ward rounds. An audit
      of induction of junior doctors highlighted concerns IMPLICATIONS: A near-peer
      departmental induction using simulated ward rounds may improve the preparedness
      of junior doctors for their role within a new department, potentially improving
      patient care and the junior doctors' learning experiences.

PMID- 25603704
TI  - Using expert consensus to develop a simulation course for faculty members.
AB  - BACKGROUND: Effective learning from simulation-based training depends on expert
      facilitation by skilled faculty members, but there are few guidelines upon which
      to base simulation development. A collaborative approach was taken in the East of
      England to determine the agreed content of such a course. METHODS: A modified
      Delphi method was used to determine consensus amongst the simulation-provider
      leads in the East of England on what should be the essential elements of a
      training course for faculty members. A questionnaire designed by a steering group
      was circulated to the consensus group, and their responses were used to modify
      subsequent questionnaires. There was enough agreement after two rounds not to
      require a third round. RESULTS: After two rounds there was high level of
      agreement that the educational content should include scenario design, creating a
      supportive learning environment, structured debriefing formats, human factors,
      educational feedback and communication. There was also agreement on preferred
      teaching methods, minimum qualification and continuing development for faculty
      members. There was moderate agreement on the prior experience required of faculty
      members, and no agreement on the costs of courses. Effective learning from
      simulation-based training depends upon expert facilitation by skilled faculty
      members DISCUSSION: By using a consensus method to determine the content and
      format of a simulation development course designed for faculty members, there is
      agreement in the East of England on what constitutes an educationally sound
      programme. This should provide assurance to both simulation providers and
      commissioners of education that despite the absence of guidelines, there is an
      agreed practice standard for simulation-based training in the region.

PMID- 25603705
TI  - Clinical simulation practise framework.
AB  - BACKGROUND: Historically, simulation has mainly been used to teach students hands
      on skills in a relatively safe environment. With changes in the patient
      population, professional regulations and clinical environments, clinical
      simulation practise (CSP) must assist students to integrate and apply their
      theoretical knowledge and skills with their critical thinking, clinical
      judgement, prioritisation, problem solving, decision making, and teamwork skills
      to provide holistic care and treatment to their patients. CONTEXT: CSP holds
      great potential to derive a positive transformation in students' transition into
      the workplace, by associating and consolidating learning from classrooms to
      clinical settings, and creating bridges between theory and practice. For CSP to
      be successful in filling the gap, the design and management of the simulation is
      crucial. INNOVATION: In this article a new framework called 'Clinical simulation
      practise framework: A knowledge to action strategy in health professional
      education' is being introduced that aims to assist educators and curriculum
      developers in designing and managing their simulations. This CSP framework
      theorises that simulation as an experiential educational tool could improve
      students' competence, confidence and collaboration in performing professional
      practice in real settings if the CSP provides the following three dimensions: (1)
      a safe, positive, reflective and fun simulated learning environment; (2)
      challenging, but realistic, and integrated simulated scenarios; and (3)
      interactive, inclusive, interprofessional patient-centred simulated practise.

PMID- 25603706
TI  - Real engagement improving paramedic attitudes towards the elderly.
AB  - BACKGROUND: Negative attitudes adversely impact on patient care and outcomes.
      Given the aging population in Australia, it is inevitable that paramedic
      attendance to this demographic of patients will also rise. It is therefore
      imperative that undergraduate paramedic attitudes towards elderly patients are
      investigated, along with pedagogical approaches to maintain or enhance them.
      METHODS: Eleven second-year paramedic students enrolled in Monash University's
      Bachelor of Emergency Health (Paramedic) degree, came together with 11
      independently living elderly residents from Patterson Lakes Village and
      participated in an engagement activity. The Aging Semantic Differential (ASD)
      survey and focus groups were used to analyse the students' attitudes towards the
      elderly, before and after the activity. RESULTS: Students showed improved
      attitudes toward the elderly across two of the three ASD dimensions. Focus group
      discussions suggested that students found the elderly participants to be more
      independent and capable than they had first thought, but were unchanged on their
      attitude with regard to elderly people being inflexible. CONCLUSION: Students
      were presented with an opportunity to actively engage with independently living
      elderly patients. This experience challenged their preconceived ideas about the
      elderly and their capabilities, and at a minimum increased awareness, which will
      assist future paramedics in their interactions and care of these patients.

PMID- 25603707
TI  - Does a high ranking mean success in the Situational Judgement Test?
AB  - BACKGROUND AND PURPOSE: The selection of medical students to the foundation
      programme has undergone several changes since its introduction in 2005, with the
      latest being the introduction of the Situational Judgement Test (SJT) in 2013.
      The SJT, a 2-hour exam that uses a multiple-choice format to assess an
      individual's judgement when presented with clinically related scenarios, now
      accounts for 50 per cent of the application process. The remaining 50 per cent is
      made up of the Educational Performance Measure (EPM) score, which includes the
      medical student's performance at medical school, allocated by points attributed
      according to decile ranking. Coming out of its pilot year, there is little
      research into the results of the SJT. This project aims to discover whether there
      is a correlation between high-performing students who succeeded at medical school
      (i.e. by decile ranking) and those who scored high in the SJT. This project aims
      to discover whether there is a correlation between high- performing students and
      those whoscored high in the SJT METHOD: A survey was circulated to fifth-year
      medical students across the UK applying to the foundation programme in 2013, and
      who had sat the pilot year of the SJT. Students were asked to enter numerical
      values for their EPM and SJT scores. RESULTS: A total of 239 students from 12 UK
      medical schools responded to the questionnaire. In addition to their EPM,
      academic and SJT scores, all participants provided data on gender, duration of
      course (i.e. 4 or 5 years) and whether or not additional resources were used for
      the SJT. There was no correlation between the SJT and the academic scores
      (Spearman's = 0.0458; probability of any relationship = 0.4865).

PMID- 25603708
TI  - Why do students participate in medical education?
AB  - BACKGROUND: Medical student involvement in curriculum development is important;
      however, little is known about why medical students become engaged in this
      activity. The aim of this study was to understand what motivates medical students
      at one university to participate in the process of curriculum development and
      gain a wider perspective on student engagement in medical education. METHODS:
      Grounded theory methodology was the foundation of this study. We conducted semi
      structured interviews with seven medical students from the University of Tokyo
      who developed and participated in a group whose aim was to actively contribute
      towards improving their medical education. The data from the interviews were
      analysed by thematic synthesis, with triangulation. RESULTS: Three themes emerged
      as potential explanations for motivating student behaviour: (1) extracurricular
      interaction with faculty members; (2) engaging with highly motivated peers; and
      (3) student values for serving the public. CONCLUSIONS: Students working to
      improve educational processes at their medical schools had the opportunity to
      communicate more with faculty members, enjoyed opportunities for networking with
      other highly motivated peers and enhanced aspects of their developing
      professionalism.

PMID- 25603709
TI  - Faculty member feedback reports.
AB  - BACKGROUND: Obtaining sufficient written feedback from faculty members on
      clerkship student evaluations is challenging. Few successful interventions,
      however, have been published on improving written feedback or evaluation content.
      METHODS: We evaluated and scored medicine clerkship student evaluation forms from
      one academic year (2011/12) for timeliness, grade distribution and the number of
      written comments. Based on this assessment, faculty members received a feedback
      report documenting their performance at the end of the year to encourage
      improvement. Medicine clerkship student evaluation forms were scored again for
      the same criteria the following academic year (2012/13) to ascertain the impact
      of the feedback reports on evaluation timeliness, grade distribution and the
      number of written comments. RESULTS: Sixty-one faculty members completed student
      clerkship evaluations in both years, and received feedback reports. There was no
      change in the overall timeliness, grade distribution or number of written
      comments. There were 13 faculty members (21%) identified as 'low performing', who
      were responsible for 75 per cent (21/28) of the evaluation forms without any
      written comments. Within this subgroup, the proportion of evaluation forms with
      comprehensive comments (mostly sentences) increased after implementing the
      feedback reports [3/42 (7%) versus 9/25 (36%), p = 0.006]. Obtaining sufficient
      written feedback from faculty members on clerkship student evaluations is
      challenging DISCUSSION: At our institution, the majority of inadequately
      completed clerkship evaluation forms are generated by a small group of low
      performing faculty members. Providing feedback to these faculty members about
      their student evaluations was associated with improved performance the next year.
      Targeted feedback to low-performing faculty members may be an effective strategy
      to improve student evaluations.

PMID- 25603710
TI  - Hospitalist workload and resident evaluations.
AB  - BACKGROUND: Most academic hospitalists fulfil the role of clinician educator and
      have many opportunities for the bedside clinical teaching of resident physicians;
      however, hospitalists are promoted at lower rates than traditional internal
      medicine faculty staff. The conflict between the demands of clinical productivity
      and time to teach may be central to understanding the lower rates of academic
      promotion seen in hospitalists. This investigation explores the relationship
      between clinical productivity and learner evaluations of hospitalist clinician
      educators. METHODS: A retrospective review of clinical productivity and learner
      evaluations of hospitalists by residents was collected during the 2009-2012
      academic years at Southern Illinois University School of Medicine. Correlation
      analysis between annual work relative value units (wRVUs), patient encounters and
      duty days with resident evaluations of faculty staff in the Accreditation Council
      for Graduate Medical Education core competencies was performed. RESULTS: Forty
      one annual data sets, representing 18 individual hospitalists, were analysed. No
      significant correlations between clinical productivity, in terms of annual work
      RVUs, patient encounters and duty days, and resident learner evaluation scores
      was found. This investigation explores the relationship between clinical
      productivity and learner evaluations of hospitalist clinician educators
      DISCUSSION: This study found no significant influence of measures of annual
      clinical service workload on resident learner evaluations of hospitalist clinical
      educators. These results are consistent with data reported for emergency medicine
      doctors and anaesthesiologists. These results may have significant implications
      for the staffing requirements for academic hospitalists.

PMID- 25603711
TI  - A holistic approach to course evaluation.

PMID- 25603712
TI  - Lost in translation: X-ray teaching in Africa.

PMID- 25603713
TI  - The heart exposed: learning from pigs.

PMID- 25603716
TI  - Balancing act of undergraduate clinical teaching.

PMID- 25603717
TI  - Sexual arousal: the correspondence of eyes and genitals.
AB  - Men's, more than women's, sexual responses may include a coordination of several
      physiological indices in order to build their sexual arousal to relevant targets.
      Here, for the first time, genital arousal and pupil dilation to sexual stimuli
      were simultaneously assessed. These measures corresponded more strongly with each
      other, subjective sexual arousal, and self-reported sexual orientation in men
      than women. Bisexual arousal is more prevalent in women than men. We therefore
      predicted that if bisexual-identified men show bisexual arousal, the
      correspondence of their arousal indices would be more female-typical, thus
      weaker, than for other men. Homosexual women show more male-typical arousal than
      other women; hence, their correspondence of arousal indices should be stronger
      than for other women. Findings, albeit weak in effect, supported these
      predictions. Thus, if sex-specific patterns are reversed within one sex, they
      might affect more than one aspect of sexual arousal. Because pupillary responses
      reflected sexual orientation similar to genital responses, they offer a less
      invasive alternative for the measurement of sexual arousal. 

PMID- 25603718
TI  - Adolescents who perceive fewer consequences of risk-taking choose to switch off
      games later at night.
AB  - AIM: Technology use by adolescents close to bedtime commonly leads to sleep
      problems, and individual factors predicting those at heightened risk are under
      studied. We investigated whether risk-taking perceptions influenced length of
      adolescent technology use at bedtime and whether being aware of time moderated
      this association. METHODS: We recruited 16 males and five females, with a mean
      age of 17.6 years, from school and university populations to assess adolescent
      technology use and bedtimes. They were assessed for trait risk-taking using the
      Cognitive Appraisal of Risky Events questionnaire and had unrestrained access to
      a video game on two separate nights, counterbalanced for clock present or clock
      absent conditions. The adolescents' self-selected bedtime provided a measure of
      the level of technology use and was the dependent variable. RESULTS: Adolescents
      who perceived fewer negative consequences of risky activities on the Cognitive
      Appraisal of Risky Events played the video game longer and went to bed later than
      those who perceived more negative consequences (p = 0.03). There was no influence
      on bedtimes from perceived benefits of risk-taking or clock presence. CONCLUSION:
      Adolescents who perceived fewer negative consequences of risk-taking were more
      likely to stay up later using technology, facing a heightened risk of displaced
      sleep.

PMID- 25603719
TI  - How does salinity influence habitat selection and growth in juvenile American
      eels Anguilla rostrata?
AB  - The influence of salinity on habitat selection and growth in juvenile American
      eels Anguilla rostrata captured in four rivers across eastern Canada was assessed
      in controlled experiments in 2011 and 2012. Glass eels were first categorized
      according to their salinity preferences towards fresh (FW), salt (SW) or brackish
      water (BW) and the growth rate of each group of elvers was subsequently monitored
      in controlled FW and BW environments for 7 months. Most glass eels (78-89%) did
      not make a choice, i.e. they remained in BW. Salinity preferences were not
      influenced by body condition, although a possible role of pigmentation could not
      be ruled out. Glass eels that did make a choice displayed a similar preference
      for FW (60-75%) regardless of their geographic origin but glass eels from the St
      Lawrence Estuary displayed a significantly higher locomotor activity than those
      from other regions. Neither the salinity preferences showed by glass eels in the
      first experiment nor the rearing salinities appeared to have much influence on
      growth during the experiments. Elvers from Nova Scotia, however, reached a
      significantly higher mass than those from the St Lawrence Estuary thus supporting
      the hypothesis of genetically (or epigenetically) based differences for growth
      between A. rostrata from different origins. These results provide important
      ecological knowledge for the sustained exploitation and conservation of this
      threatened species.

PMID- 25603721
TI  - Phage lytic proteins: biotechnological applications beyond clinical
      antimicrobials.
AB  - Most bacteriophages encode two types of cell wall lytic proteins: endolysins
      (lysins) and virion-associated peptidoglycan hydrolases. Both enzymes have the
      ability to degrade the peptidoglycan of Gram-positive bacteria resulting in cell
      lysis when they are applied externally. Bacteriophage lytic proteins have a
      demonstrated potential in treating animal models of infectious diseases. There
      has also been an increase in the study of these lytic proteins for their
      application in areas such as food safety, pathogen detection/diagnosis, surfaces
      disinfection, vaccine development and nanotechnology. This review summarizes the
      more recent developments, outlines the full potential of these proteins to
      develop new biotechnological tools and discusses the feasibility of these
      proposals. 

PMID- 25603720
TI  - STK33 overexpression in hypopharyngeal squamous cell carcinoma: possible role in
      tumorigenesis.
AB  - BACKGROUND: The role of serine/threonine kinase 33 (STK33) gene in tumorigenesis
      is still controversial. This study was aimed to investigate whether STK33 had the
      effect on hypopharyngeal squamous cell carcinoma (HSCC) and relevant genes, as
      well as the potential relation to ERK1/2 pathway. METHODS: Immunohistochemistry
      was performed to investigate STK33 expression in human HSCC specimens. MTT,
      immunofluorescence, clone formation and matrigel invasion assays were employed to
      detect the effects of STK33 knockdown (STK33-RNAi) and/or PD98059 on major
      oncogenic properties of a HSCC cell line (Fadu), while, real-time PCR and western
      blot were used to examine the expressions of relevant genes. RESULTS: STK33 was
      over-expressed in HSCC specimens, which was significantly associated with certain
      clinicopathological parameters. STK33-RNAi in Fadu cells resulted in inhibition
      of proliferation, induction of apoptosis, reduction of clone formation, and
      decline in the migration and invasion. These effects were potentiated by
      administration of PD98059. Mechanistic studies revealed that STK33-RNAi led to an
      increase in Caspse-3, Nm-23-H1 and E-Cadherin expressions and a reduction in Bcl
      2, Ki-67 and Vimentin expressions. Moreover, PD98059 significantly reduced both
      ERK1/2 and STK33 expressions in Fadu cells. CONCLUSIONS: STK33 is a potential
      oncogene and a promising diagnostic marker for HSCC. STK33 may promote
      tumorigenesis and progression of HSCC, and serve as a valuable molecular target
      for treatment of HSCC.

PMID- 25603722
TI  - Golden rice: scientific, regulatory and public information processes of a
      genetically modified organism.
AB  - Historically, agricultural development evolved in three phases. During the first
      phase the plants were selected on the basis of the availability of a plant with
      desirable properties at a specific location. The second phase provided the
      agricultural community with crossbreeding plants to achieve improvement in
      agricultural production. The evolution of biological knowledge has provided the
      ability to genetically engineer (GE) crops, one of the key processes within
      genetically modified organisms (GMO). This article uses golden rice, a species of
      transgenic Asian rice which contains a precursor of vitamin A in the edible part
      of the plant as an example of GE/GMO emphasizing Chinese experience in
      agricultural evolution. It includes a brief review of agricultural evolution to
      be followed by a description of golden rice development. Golden rice was created
      as a humanitarian project and has received positive comments by the scientific
      community and negative voices from certain environmental groups. In this article,
      we use the Best Available Science (BAS) Concept and Metrics for Evaluation of
      Scientific Claims (MESC) derived from it to evaluate claims and counter claims on
      scientific aspects of golden rice. This article concludes that opposition to
      golden rice is based on belief rather than any of its scientifically derived
      nutritional, safety or environmental properties. 

PMID- 25603724
TI  - Estrogen and progesterone receptor subtype expression in granulosa cells from
      women with polycystic ovary syndrome.
AB  - We evaluated gene expression of estrogen and progesterone nuclear receptors in
      granulosa cells (GCs) of polycystic ovary syndrome (PCOS) women compared to women
      with normal cycling ovaries (control group) to achieve a better understanding of
      ovarian steroid status in patients with PCOS. In this prospective study, 40
      patients with PCOS and 40 women with normal ovulatory function who underwent in
      vitro fertilization (IVF) for treatment of tubal and/or male infertility were
      recruited. Follicular fluid was collected from patients and GCs were isolated
      from follicular fluid and then were purified with Micro Beads conjugated to
      monoclonal anti-human CD45 antibodies. RNA was extracted and reverse
      transcription was performed. Gene expression of estrogen and progesterone
      receptors was determined by quantitative real time PCR (qRT-PCR). Estrogen
      receptor beta (ERbeta) expression was significantly higher than ERalpha
      expression in both groups (p < 0.002). ERalpha and ERbeta mRNA expression in PCOS
      was significantly lower than control group (p < 0.002). The expression levels of
      PRA and PRB in PCOS was significantly lower than control group (p < 0.002). In
      conclusion, a significant reduction of these genes in GCs from follicles of women
      with PCOS could be considered as a sign for maturation defect or follicular
      arrest in GCs. 

PMID- 25603726
TI  - Asparaginase Therapy in Pediatric Acute Lymphoblastic Leukemia: A Focus on the
      Mode of Drug Resistance.
AB  - Asparaginase is one of the most important chemotherapeutic agents against
      pediatric acute lymphoblastic leukemia (ALL), the most common form of childhood
      cancer. The therapeutic efficacy (e.g., chemoresistance) and adverse effects of
      asparaginase (e.g., hypersensivity and pancreatitis) have been investigated over
      the past four decades. It was suggested early on that leukemic cells are
      resistant to asparaginase because of their increased asparagine synthetase
      activity. Afterward, other mechanisms associated with asparaginase resistance
      were reported. Not only leukemic cells but also patients themselves may play a
      role in causing asparaginase resistance, which has been associated with
      unfavorable outcome in children with ALL. This article will briefly review
      asparaginase therapy in children with ALL and comprehensively analyze recent
      reports on the potential mechanisms of asparaginase resistance.

PMID- 25603723
TI  - Gender bias in lupus: does immune response initiated in the gut mucosa have a
      role?
AB  - The risk of developing systemic lupus erythematosus (SLE) is approximately nine
      times higher among women compared to men. However, very little is understood
      concerning the underlying mechanisms that contribute to this gender bias.
      Further, whether there is a link between immune response initiated in the gut
      mucosa, the progression of SLE and the associated gender bias has never been
      investigated. In this report, we show a potential link between the immune
      response of the gut mucosa and SLE and the gender bias of lupus for the first
      time, to our knowledge. Both plasma cell- and gut-imprinted- alpha4beta7 T cell
      frequencies were significantly higher in the spleen and gut mucosa of female (SWR
      * NZB)F1 (SNF1 ) mice compared to that of their male counterparts. Importantly,
      female SNF1 mice not only showed profoundly higher CD45(+) immune cell densities,
      but also carried large numbers of interleukin (IL)-17-, IL-22- and IL-9-producing
      cells in the lamina propria (LP) compared to their male counterparts. Intestinal
      mucosa of female SNF1 mice expressed higher levels of a large array of
      proinflammatory molecules, including type 1 interferons and Toll-like receptors 7
      and 8 (TLR-7 and TLR-8), even before puberty. Our work, therefore, indicates that
      the gut immune system may play a role in the initiation and progression of
      disease in SLE and the associated gender bias. 

PMID- 25603725
TI  - Effects of Two Different Exogenous Surfactant Preparations on Serial Peripheral
      Perfusion Index and Tissue Carbon Monoxide Measurements in Preterm Infants with
      Severe Respiratory Distress Syndrome.
AB  - BACKGROUND: Administration of an exogenous surfactant may affect both ventilatory
      and hemodynamic parameters in preterm infants with respiratory distress syndrome
      (RDS). Peripheral perfusion may be expected to be influenced, and serial
      perfusion index (PI) values may show this effect. Noninvasive transcutaneous
      carbon monoxide (TCO) monitoring may show RDS severity, oxidative and
      inflammatory stress, and response to surfactant treatment. METHODS: This
      randomized controlled nonblinded study was performed in 30 preterm infants with
      RDS, treated with poractant alfa (n = 15) or beractant (n = 15); 18 preterm
      infants without RDS served as a control group. Oxygenation and hemodynamic
      parameters were recorded and compared through the first 6 hours of treatment. PI
      and TCO values were measured prior to (Tp), immediately after (T0), and at 5
      minutes (T5), 30 minutes (T30), 60 minutes (T60), and 360 minutes (T360) after
      the bolus surfactant administration. The mean arterial pressure, oxygenation
      index, pH, and lactate levels were recorded simultaneously. RESULTS: Both study
      groups had lower Tp PI and higher Tp TCO levels than controls. Both surfactant
      preparations improved the PI, TCO, mean arterial pressure, oxygenation index, pH,
      and lactate levels at the end point of T360. However, the median Tp PI value of
      1.3 first decreased to 0.86 at T0 (P < 0.001), and then it increased to 0.99 at
      T5 (p < 0.001) and to 1.25 at T30 (p = 0.037). The median Tp TCO value of 3
      decreased to 2, 1.5, 0, and 0 at T0, T5, T30, and T60, respectively (p < 0.001).
      PI more quickly recovered to Tp values (30 minutes vs. 60 minutes) and reached
      the control group values (30 minutes vs. 360 minutes) with beractant compared to
      that with poractant alfa. TCO recovered to Tp values in both groups at the same
      time (5 minutes vs. 5 minutes), but reached the control group values more quickly
      (5 minutes vs. 30 minutes) with poractant alfa than with beractant. CONCLUSION:
      Patients with RDS had poor perfusion, and PI improved with both surfactant
      preparations only following a short decline in the 1(st) minute. The expected
      improvement of PI occurred earlier in the beractant subgroup. TCO declined in
      both groups, showing lung improvement and decreased oxidative/inflammatory
      stress, and it was normalized earlier with poractant alfa.

PMID- 25603727
TI  - Prevalence of Growth Disorders in a Nationally Representative Sample of Iranian
      Adolescents According to Socioeconomic Status: The CASPIAN-III Study.
AB  - BACKGROUND: This study aims to assess the prevalence of growth disorders among a
      nationally representative sample of Iranian adolescents according to the
      socioeconomic status (SES) of their living area. METHODS: This nationwide cross
      sectional survey was conducted among a representative sample of 5624 adolescents
      aged 10-18 years. They were selected by multistage cluster sampling from 27
      provinces of Iran. Subnational classification of the country was based on
      geography and social class of each region. Analysis of variance and Chi-square
      tests were used to compare the prevalence of growth disorders according to sex
      and SES of the living regions. RESULTS: The mean and standard deviation for body
      mass index was 19.42 (4.09) kg/m(2), with a significant trend from the Southeast
      region with lowest SES to the Central part with highest SES (p(trend) < 0.001).
      The prevalence of obesity, combined overweight and obesity, as well as abdominal
      adiposity increased with a significant trend from low to high SES (all p(trend) <
      0.001, except for girls' height, p(trend) = 0.003). The opposite direction was
      documented for the prevalence of underweight and short stature, with the highest
      frequencies in the Southeast (lowest SES) and the lowest in Central part (highest
      SES). CONCLUSION: Excess weight was more prevalent in high SES regions, whereas
      underweight and short stature were more prevalent in low SES regions. These
      findings underscore the necessity of implementing evidence-based health promotion
      programs and preventive strategies according to SES.

PMID- 25603728
TI  - Enhanced camptothecin production by ethanol addition in the suspension culture of
      the endophyte, Fusarium solani.
AB  - Ethanolic extract of a non-camptothecin producing plant, Catharanthus roseus when
      added in the suspension culture of the endophyte Fusarium solani known to produce
      camptothecin, resulted in enhanced production of camptothecin by 10.6-fold in
      comparison to that in control (2.8 MUg/L). Interestingly, addition of pure
      ethanol (up to 5% v/v) in the suspension culture of F. solani resulted in maximum
      enhancement in camptothecin production (up to 15.5-fold) from that obtained in
      control. In the presence of ethanol, a reduced glucose uptake (by ~ 40%) and
      simultaneous ethanol consumption (up to 9.43 g/L) was observed during the
      cultivation period (14 days). Also, the total NAD level and the protein content
      in the biomass increased by 3.7- and 1.9-fold, respectively, in comparison to
      that in control. The study indicates a dual role of ethanol, presumably as an
      elicitor and also as a carbon/energy source, leading to enhanced biomass and
      camptothecin production.

PMID- 25603729
TI  - Long-term operation of manure-microbial fuel cell.
AB  - Microbial fuel cell (MFC) is applied to produce electricity using dairy manure as
      a fuel. Since the way MFC utilizes manure as a fuel and the long-term operation
      stability of manure-MFC remains unclear, this study examined the evolution of
      dissolved organic matter (DOM) in anodic chamber and power generation by MFC in a
      171days test. The tested MFC can produce electricity over the entire testing
      period by single feed of manure, with stable power output and total chemical
      oxygen demand (TCOD) removal rate in the period of day 30-140. The hydrophobic
      acid (HPO-A) and hydrophilic (HPI) fractions of manure were the principal
      components of anolyte DOM, with the concentrations of both being reduced over MFC
      operation. The degradable organic matters were converted to compounds with high
      aromaticity. 

PMID- 25603730
TI  - Conversion of rice straw to monomeric phenols under supercritical methanol and
      ethanol.
AB  - Hydrothermal liquefaction of rice straw has been carried out using various
      organic solvents (CH3OH, C2H5OH) at different temperatures (250, 280 and 300 
      degrees C) and residence times (15, 30 and 60 min) to understand the effect of
      solvent and various reaction parameters on product distribution. Maximum liquid
      product yield (47.52 wt%) was observed using ethanol at 300  degrees C and 15 min
      reaction time. FTIR and NMR ((1)H and (13)C) of liquid product indicate that
      lignin in rice straw was converted to various monomeric phenols. GC-MS of the
      liquid product showed the presence of various phenol and guaiacol derivatives.
      Main compounds observed in liquid product were phenol, 4-ethylphenol, 4-ethyl-2
      methoxyphenol (4-ethylguaiacol), 2,6-dimethoxyphenol (syringol), 2-isopropyl-5
      methylphenol (thymol). Powder XRD and SEM of bio-residue showed that rice straw
      was decomposed to low molecular weight monomeric phenols.

PMID- 25603731
TI  - Using transcranial magnetic stimulation to quantify electrophysiological changes
      following concussive brain injury: a systematic review.
AB  - Mild traumatic brain injury (mTBI) and sports concussion are a growing public
      health concern, with increasing demands for more rigorous methods to quantify
      changes in the brain post-injury. Electrophysiology, and in particular,
      transcranial magnetic stimulation (TMS), have been demonstrated to provide
      prognostic value in a range of neurological conditions; however, no review has
      quantified the efficacy of TMS in mTBI/concussion. In the present study, we
      present a systematic review and critical evaluation of the scientific literature
      from 1990 to 2014 that has used TMS to investigate corticomotor excitability
      responses at short-term (< 12 months), medium-term (1-5 years), and long-term (>
      5 years) post-mTBI/concussion. Thirteen studies met the selection criteria, with
      six studies presenting short-term changes, five studies presenting medium-term
      changes, and two studies presenting long-term changes. Irrespective of time post
      concussion, change in intracortical inhibition was the most reported observation.
      Other findings included increased stimulation threshold, and slowed neurological
      conduction time. Although currently limited, the data suggest that TMS has
      prognostic value in detecting neurophysiological changes post-mTBI/concussion.

PMID- 25603732
TI  - Alendronate rescued osteoporotic phenotype in a model of glucocorticoid-induced
      osteoporosis in adult zebrafish scale.
AB  - Long-term effects of glucocorticoid treatment in humans induce bone loss and
      increase the risk of fracture in the skeleton. The pathogenic mechanisms of
      glucocorticoid-induced osteoporosis (GIOP) are still unclear. The GIOP and its
      effects have been reproduced in several animal models including Danio rerio
      (zebrafish) embryo. The treatment of adult fish with prednisolone (PN) has shown
      a dose-dependent decrease of mineralized matrix in the scales. Large resorption
      lacunae are characterized by single TRAP-positive cells which migrate to the
      margin of the scale merging into a multinucleated structures. The treatment with
      PN of cultured scales did not increase TRAP activity suggesting that the massive
      presence of osteoclasts in the resorption sites could be likely the result of a
      systemic recruitment of monocyte-macrophage precursors. We observed that
      treatment with PN induced a significant decrease of the alkaline phosphatase
      (ALP) activity in scale scleroblasts if compared with untreated controls. Then,
      we investigated the total mineral balance under prednisolone treatment using a
      time-dependent double live staining. The untreated fish fully repaired the
      resorption lacuna induced by prednisolone, whereas treated fish failed. The
      presence of osteoclast resorption fingerprints on new matrix suggested that the
      osteoclast activity counterbalances the osteodepositive activity exerted by
      scleroblasts. The treatment with PN in association with alendronate (AL) has
      surprisingly resulted in a significant decrease of TRAP activity and increase of
      ALP compared to PN-treated fish in biochemical and histological assays confirming
      the action of alendronate against GIOP in fish as well in humans. 

PMID- 25603733
TI  - Anesthetic management of pediatric patients with Emanuel syndrome.
AB  - Emanuel syndrome is a rare anomaly associated with multiple systemic
      malformations. We present two cases involving pediatric patients with Emanuel
      syndrome. The first patient presented with micrognathia and had patent ductus
      arteriosus and a single kidney. The patient was difficult to intubate with
      McGRATH((r)) but was successfully intubated with an Airtraq((r)) device. The
      second patient did not present with micrognathia and was not difficult to
      intubate. A thorough examination of the heart, kidney, and spinal cord is
      important when planning the anesthetic management of patients with Emanuel
      syndrome. Moreover, adequate preparation for a difficult airway is essential, and
      the Airtraq((r)) device may be useful for intubating patients with Emanuel
      syndrome with micrognathia. 

PMID- 25603734
TI  - Phosphoenolpyruvate administration protects ischemia-reperfusion injury in
      isolated rabbit lungs.
AB  - Phosphoenolpyruvate (PEP) is an intermediate metabolite of the glycolytic pathway
      and an in vivo high-energy phosphate compound. We have examined the protective
      effects of PEP on ischemia-reperfusion lung injury in isolated rabbits lungs
      perfused with a physiological salt solution. The lungs were divided into three
      treatment groups: (1) ischemia-reperfusion (IR), (2) ischemia-reperfusion with
      PEP treatment (PEP-IR), in which 1 mM PEP was pre-administered into the perfusate
      during the stable period, and (3) ventilation-perfusion continued without
      interruption (Cont). In the IR and PEP-IR groups, ventilation-perfusion was
      discontinued for about 60 min after a 30-min stable period and then restarted.
      The capillary filtration coefficients (K fc) and pyruvate concentration in the
      perfusate were determined immediately before ischemia and 30 and 60 min after
      reperfusion. The left lungs were dried at the end of the experiment to calculate
      the tissue wet-to-dry weight ratio (W/D). The K fc values after reperfusion were
      significantly higher in the IR group than in the other two groups. Pyruvate
      concentrations were significantly higher at three time-points in the PEP-IR group
      than in the other two groups. The W/D was significantly higher in the IR group
      than in the other two groups. Based on these results, we conclude that the
      administration of PEP prior to lung ischemia alleviates lung ischemia-reperfusion
      injury.

PMID- 25603735
TI  - Consent: a practical guide.
AB  - Societal change through an increase in knowledge and accessibility of education
      as well as a push for autonomy has contributed to a shift in the balance of power
      from clinician to patient (especially in the last 20 years). This drive for
      personal autonomy has seen a shift from medical paternalism, a consequence of
      ignorance, to personal autonomy, a continuously evolving by-product of 17th
      century liberalism as expressed and facilitated by access of information.
      Consequently, patient-centred care has become the new standard for health care
      involving a two-way communication process of shared information and informed
      decision-making. At its centre is the patient's right to accept or decline
      treatment recommended by a clinician, be it detrimental or beneficial. Clinicians
      must recognize and appreciate this shift to patient-centred care and its legal
      ramifications. 

PMID- 25603736
TI  - Monoatomic-thick graphitic carbon nitride dots on graphene sheets as an efficient
      catalyst in the oxygen reduction reaction.
AB  - Atomically thick two-dimensional materials have been increasingly attracting
      research interest not only due to their promising applications in a range of
      functional devices but also to their theoretical value to unraveling the
      catalytic electron transfer process within a simplified scenario. In this work,
      the monoatomic-thick dot-sized graphitic carbon nitride (g-C3N4) has been
      synthesized and intimately contacted to the basal plane of the graphene sheet to
      form the monolayer g-C3N4 dots@graphene (MTCG). The electrocatalytic activity of
      the MTCG in the oxygen reduction reaction is found to rival that of the
      commercial Pt/C catalyst in terms of the catalytic current density and half-wave
      potential. The density functional theory calculations confirm the catalytic
      improvement of the MTCG originates from a higher efficiency for the reduction of
      OOH(-) than that of the g-C3N4 alone; therefore, the current work is expected to
      provide new insights in developing next-generation, highly efficient catalysts
      for the oxygen reduction reaction. 

PMID- 25603737
TI  - Reflections: reviews, reviewers.

PMID- 25603738
TI  - Comparative study of stretching modalities in healthy women: heating and
      application time.
AB  - A lack of muscle flexibility affects the functionality of the human body, making
      it difficult to carry out certain activities of daily living. The aim of the
      present study was to compare the technique of passive static stretching on
      hamstring muscles in isolation, or combined with heating techniques and different
      application times. Fifty women were randomly assigned to 5 groups (n = 10 each):
      The Microwave Diathermy Group had the hamstrings heated by microwave before
      stretching; Treadmill Group, in which warm-up walking was performed before
      stretching; 30-Second Group, in which 30 s of stretching was performed; 10-Minute
      Group, which involved stretching for 10 min and Control Group. In all groups, the
      leg extension range of motion was assessed, and the flexibility by the third
      finger-ground test was performed before and after application. The individuals in
      the experimental groups performed three stretching sessions on three consecutive
      days. All statistical analysis was performed with p <= 0.05. The results showed
      that all treatments were effective compared to the control group. The Treadmill
      Group and the 10-Minute group were superior for an acute effect (soon after the
      stretch--related to a decreased muscular viscoelasticity). The 10-Minute Group
      was the most effective for the chronic effect (long lasting--related to increased
      numbers of sarcomeres). A 10-minute stretch, when performed over four subsequent
      days, is suggested for faster increase in flexibility. The results could suggest
      a systemic warming (such as the one provided by a treadmill workout) before
      stretching for an acute gain of flexibility in the same day. It was possible to
      identify the inefficiencies associated with the use of microwaves in terms of
      stretching to gain flexibility. In fact, the values recorded were similar to
      stretching without any heat at all.

PMID- 25603739
TI  - The efficacy of surface electromyographic biofeedback assisted stretching for the
      treatment of chronic low back pain: a case-series.
AB  - Individuals with low back pain (LBP) commonly present with an impaired flexion
      relaxation (FR) response, characterised as continued lumbar muscle activation at
      maximal voluntary flexion. The aim of the present investigation was to explore
      the effectiveness of a surface electromyographic assisted stretching (SEMGAS)
      programme in improving FR. Nine volunteers with chronic LBP and an impaired FR
      took part in weekly biofeedback SEMGAS sessions and performed a home-based
      stretching programme, for 5 weeks. FR, Oswestry Disability Index, Numeric Pain
      Rating Scale and Sit and Reach were recorded pre and post-intervention as well as
      at a 4-6-week follow-up. Of the nine participants included, three improved FR to
      statistically significant levels. These three participants also achieved a
      clinically important change in pain intensity scores. The results suggest that
      SEMGAS may provide benefits to some individuals with chronic LBP and impaired FR,
      although larger scale investigation of SEMGAS alone is indicated. 

PMID- 25603740
TI  - Relationship between functional capacity, joint mobility and pulmonary function
      in patients with systemic sclerosis.
AB  - BACKGROUND: In systemic sclerosis (SS), pulmonary involvement is currently the
      leading cause of mortality. Joint impairments limit the range of motion (ROM),
      which may reduce the functional capacity of these patients. AIM: To assess the
      correlation between the functional capacity, joints mobility, and pulmonary
      function parameters in adults with SS. METHOD: This was a cross-sectional study
      including ten SS patients who underwent goniometry, spirometry, carbon monoxide
      diffusing capacity (DLco) assessment, and the 6-min walk distance (6 MWD).
      RESULTS: Significant correlations were found between the 6 MWD and the
      tibiotarsal plantarflexion ROM (r = 0.65; P < 0.01), tibiotarsal dorsiflexion ROM
      (r = 0.64; P < 0.01), and hip adduction ROM (0.52; P < 0.05). Significant
      correlation was also observed between the 6 MWD and DLco (r = 0.61; P < 0.01).
      CONCLUSIONS: Although the 6 MWD can be influenced by cardiovascular and pulmonary
      impairments in SS, our results suggest that the musculoskeletal dysfunction play
      an important role in the functional capacity of these patients.

PMID- 25603741
TI  - Creating integrative work: a qualitative study of how massage therapists work
      with existing clients.
AB  - INTRODUCTION: As one of the most often used complementary treatments, massage is
      increasingly positioned as an essential component of integrative medicine. Recent
      studies evaluate the clinical efficacy of massage therapy, but few studies
      explore how massage therapists (MTs) execute their work and exercise clinical
      reasoning in natural settings. PURPOSE: To gain foundational knowledge about
      clinical reasoning and applied knowledge, this study examined how 10 MTs executed
      an entire session with established clients. Results support translational
      research design and inform educators. METHODS: Ethnomethodology and phenomenology
      informed the qualitative design. Data were collected by videotaping actual
      sessions and interviewing the participants immediately afterward while viewing
      the videos. Computer-aided analysis identified data patterns for thematic
      interpretation. RESULTS: The MTs shared tacit knowledge that directed their work:
      a) maintaining a primarily biomechanical focus, b) prerequisite safe touch, c)
      multitasking not allowed, d) MTs assume physical risk, and e) the work affects
      multiple bodily systems. The MTs sensed effectiveness experientially by adopting
      common tactics: a) visualizing the manual engagement points, b) assuming the
      client controlled the physiological release, and c) educating the client. Within
      these commonalities, they operationalized their work in complex and singular
      ways, with the particular client relationship critical to structuring the session
      and evaluating the outcome. CONCLUSION: MTs viewed their work primarily as a
      biomechanical intervention, but understood therapeutic massage as serving
      multiple functions. Process-oriented clinical reasoning mirrored models found in
      psychotherapy and was informed by experience, intuition, and training, which
      resulted in an intentionally holistic approach.

PMID- 25603742
TI  - Effectiveness of body awareness interventions in fibromyalgia and chronic fatigue
      syndrome: a systematic review and meta-analysis.
AB  - OBJECTIVES: Patients with long-lasting pain problems often complain of lack of
      confidence and trust in their body. Through physical experiences and reflections
      they can develop a more positive body- and self-experience. Body awareness has
      been suggested as an approach for treating patients with chronic pain and other
      psychosomatic conditions. The aim of this systematic review is to assess the
      effectiveness of body awareness interventions (BAI) in fibromyalgia (FM) and
      chronic fatigue syndrome (CFS). METHODS: Two independent readers conducted a
      search on Medline, Cochrane Central, PsycINFO, Web of knowledge, PEDro and Cinahl
      for randomized controlled trials. RESULTS: We identified and screened 7.107
      records of which 29 articles met the inclusion criteria. Overall, there is
      evidence that BAI has positive effects on the Fibromyalgia Impact Questionnaire
      (FIQ) (MD -5.55; CI -8.71 to -2.40), pain (SMD -0.39, CI -0.75 to -0.02),
      depression (SMD -0.23, CI -0.39 to -0.06), anxiety (SMD -0.23, CI -0.44 to -0.02)
      and Health Related Quality of Life (HRQoL) (SMD 0.62, CI 0.35-0.90) when compared
      with control conditions. The overall heterogeneity is very strong for FIQ (I(2)
      92%) and pain (I(2) 97%), which cannot be explained by differences in control
      condition or type of BAI (hands-on/hands-off). The overall heterogeneity for
      anxiety, depression and HRQoL ranges from low to moderate (I(2) 0%-37%).
      CONCLUSIONS: Body awareness seems to play an important role in anxiety,
      depression and HRQoL. Still, interpretations have to be done carefully since the
      lack of high quality studies.

PMID- 25603744
TI  - Application of Pilates principles increases paraspinal muscle activation.
AB  - OBJECTIVE: To analyze the effect of Pilates principles on the EMG activity of
      abdominal and paraspinal muscles on stable and unstable surfaces. METHODS:
      Surface EMG data about the rectus abdominis (RA), iliocostalis (IL) and lumbar
      multifidus (MU) of 19 participants were collected while performing three
      repetitions of a crunch exercise in the following conditions: 1) with no Pilates
      technique and stable surface (nP + S); 2) with no Pilates technique and unstable
      surface (nP + U); 3) with Pilates technique and stable surface (P + S); 4) with
      Pilates and unstable surface (P + U). The EMG Fanalysis was conducted using a
      custom-made Matlab((r)) 10. RESULTS: There was no condition effect in the RA iEMG
      with stable and unstable surfaces (F(1,290) = 0 p = 0.98) and with and without
      principles (F(1,290) = 1.2 p = 0.27). IL iEMG was higher for the stable surface
      condition (F(1,290) = 32.3 p < 0.001) with Pilates principles (F(1,290) = 21.9 p
      < 0.001). The MU iEMG was higher for the stable surface condition with and
      without Pilates principles (F(1,290) = 84.9 p < 0.001).

PMID- 25603743
TI  - The Pilates breathing technique increases the electromyographic amplitude level
      of the deep abdominal muscles in untrained people.
AB  - OBJECTIVE: To evaluate the behaviour of the upper rectus abdominis, lower rectus
      abdominis and transverse abdominis/internal oblique (TrA/IO) by using surface
      electromyography during trunk flexion with and without the Pilates breathing
      technique. METHODS: Nineteen female subjects (without experience of the Pilates
      method) were recruited. The muscles were evaluated while trunk flexion was
      performed by using the Pilates breathing technique (POW) and Step Barrel device,
      followed by another contraction without the technique (NORM). Normality was
      accepted, and the paired t-test was used to determine data differences (p <
      0.05). RESULTS: Significant differences were noted in the amplitude level of
      activation between TrA/IO-POW and TrA/IO-NORM. The activation amplitude level of
      TrA/IO-POW significantly increased compared with all the other muscles under the
      NORM condition. CONCLUSION: The breathing technique of the Pilates method
      associated with trunk flexion increases TrA/IO electrical activity.

PMID- 25603745
TI  - Is pressure pain sensitivity over the cervical musculature associated with neck
      disability in individuals with migraine?
AB  - The objective was to determine if disability due to neck pain is correlated with
      pressure pain sensitivity in the cervical muscles in patients with migraine.
      Thirty-two volunteers with migraine completed the Neck Disability Index (NDI).
      Pressure pain thresholds (PPT) over the sternocleidomastoid, upper trapezius and
      suboccipital muscles were also assessed. Data were analyzed using the Spearman
      correlation coefficient (rs) and linear regression models (alpha < 0.05).
      Moderate negative correlations between NDI and PPT were obtained for the
      sternocleidomastoid (rs = -0.42; p = 0.001), upper trapezius (rs = -0.33; p =
      0.001) and suboccipital muscles (rs = -0.41; p = 0.001). The linear regression
      revealed no association between NDI and PPT of sternocleidomastoid (beta = 0.01;
      R(2) = 0.17), upper trapezius (beta = 0.01; R(2) = 0.11) and suboccipital muscles
      (beta = 0.02; R(2) = 0.17). NDI scores and PPT of the cervical muscles correlated
      moderately and was inversely proportional in patients with migraine, but the
      association was not linear, so both outcomes should be considered in the
      assessment of this population.

PMID- 25603746
TI  - Yoga therapy and ambulatory multiple sclerosis Assessment of gait analysis
      parameters, fatigue and balance.
AB  - BACKGROUND AND OBJECTIVE: Gait impairment, falls due to balance problems and
      fatigue are among the most important complaints in patients with multiple
      sclerosis (MS) and cause significant functional limitation. Use of complementary
      and alternative medicine (CAM) to help symptom management and to improve quality
      of life is growing among MS patients. Yoga is widely used as one of these CAM
      interventions, however, the number of studies that show the efficacy of yoga
      training in MS is inadequate. In this study, we aimed to evaluate the effects of
      a short term yoga program on fatigue, balance and gait in patients with MS.
      METHOD: Eight volunteer ambulatory MS patients with clinically definite relapsing
      remitting MS whose Expanded Disability Status Score (EDSS) is less than or equal
      to 6.0, and eight healthy subjects were included in the study. Patients
      participated in 12 weeks of a bi-weekly yoga program under supervision. At their
      baseline and after yoga therapy, the Fatigue Severity Scale (FSS) and Berg
      Balance Scale (BBS) are used to assess fatigue and balance. Three dimensional
      gait analysis is done using the Vicon 612 system with six cameras and two Bertec
      force plates, before and after therapy. RESULTS: After short term yoga therapy,
      statistically significant achievements were obtained in fatigue, balance, step
      length and walking speed. Although sagittal plane pelvis and hip angles, ankle
      plantar flexor moment, powers generated at the hip and ankle joints at the pre
      swing were improved, the improvements were not statistically significant.
      CONCLUSION: Yoga therapy is a safe and beneficial intervention for improving
      fatigue, balance and spatiotemporal gait parameters in patients with MS. Further
      studies with a larger sample size and longer follow-up will be needed to evaluate
      the long term effects of yoga therapy.

PMID- 25603747
TI  - Effectiveness of a program of therapeutic exercises on the quality of life and
      lumbar disability in women with Stress Urinary Incontinence.
AB  - Stress Urinary Incontinence (SUI) is a common condition and can cause social
      isolation and decreased quality of life. The literature demonstrates that
      perineal exercises are effective in promoting urinary continence and lumbar
      stability. This uncontrolled (group) pilot study, using a pre-test-post-test
      design, investigated whether a weekly session of Holistic Gymnastics((r))
      conducted during a one-year period, could change outcomes in a group of twenty
      women diagnosed with SUI. In the first and last evaluation, the subjects
      underwent a clinical examination and were asked to complete two questionnaires,
      one regarding quality of life and the other about lumbar disability. Improvement
      in the quality of life was observed in nine out of ten domains. There was also an
      improvement in lumbar disability. These results suggest that a program with
      therapeutic exercises can be effective in controlling urinary incontinence and
      improve the quality of life and lumbar disability in woman with SUI. 

PMID- 25603748
TI  - Myofascial origin of shoulder pain: a literature review.
AB  - BACKGROUND: Shoulder pain is a common problem imposing a considerable burden on
      the affected person and society. Since interventions targeting traditional
      musculoskeletal conditions are usually only moderately effective, myofascial
      origin can be suggested as an alternative possible source of shoulder pain.
      OBJECTIVES: To examine current evidence associated with myofascial origin of
      shoulder pain, with emphasis on diagnosis, prevalence and treatment efficacy.
      METHODS: PubMed, Google Scholar and PEDro databases were searched from inception
      until December 2013 for terms relating to myofascial pain in the shoulder area.
      RESULTS: Two studies showed a high reliability of the following diagnostic
      characteristics during palpation: presence or absence of the taut band, spot
      tenderness, jump sign, pain recognition and referred pain sensation. Three
      prevalence studies showed a significant greater number of active myofascial
      trigger points (MTrPs) on the painful shoulder side. Reduced muscle strength,
      accelerated muscle fatigue, inconsistent muscle activation pattern under load and
      reduced antagonist reciprocal inhibition were found in subjects with latent MTrPs
      in four observational studies. Six interventional studies demonstrated the
      effectiveness of dry needling, myofascial manipulation, ischemic compression,
      laser therapy and multimodal treatment. CONCLUSION: MTrPs in shoulder muscles is
      a common condition among patients with shoulder complaints and can be reliably
      diagnosed by palpation. The reviewed interventions seem to be effective in
      reducing pain, increasing range of motion and improving function of the painful
      shoulder.

PMID- 25603749
TI  - Effectiveness of myofascial release: systematic review of randomized controlled
      trials.
AB  - INTRODUCTION: Myofascial release (MFR) is a form of manual therapy that involves
      the application of a low load, long duration stretch to the myofascial complex,
      intended to restore optimal length, decrease pain, and improve function.
      Anecdotal evidence shows great promise for MFR as a treatment for various
      conditions. However, research to support the anecdotal evidence is lacking.
      OBJECTIVE: To critically analyze published randomized controlled trials (RCTs) to
      determine the effectiveness of MFR as a treatment option for different
      conditions. DATA SOURCES: Electronic databases: MEDLINE, CINAHL, Academic Search
      Premier, Cochrane library, and Physiotherapy Evidence Database (PEDro), with key
      words myofascial release and myofascial release therapy. No date limitations were
      applied to the searches. STUDY SELECTION: Articles were selected based upon the
      use of the term myofascial release in the abstract or key words. The final
      selection was made by applying the inclusion and exclusion criteria to the full
      text. Studies were included if they were English-language, peer-reviewed RCTs on
      MFR for various conditions and pain. DATA EXTRACTION: Data collected were number
      of participants, condition being treated, treatment used, control group, outcome
      measures and results. Studies were analyzed using the PEDro scale and the Center
      for Evidence-Based Medicine's Levels of Evidence scale. CONCLUSIONS: The
      literature regarding the effectiveness of MFR was mixed in both quality and
      results. Although the quality of the RCT studies varied greatly, the result of
      the studies was encouraging, particularly with the recently published studies.
      MFR is emerging as a strategy with a solid evidence base and tremendous
      potential. The studies in this review may help as a respectable base for the
      future trials.

PMID- 25603750
TI  - Conservative treatment of carpal tunnel syndrome: comparison between laser
      therapy and Fascial Manipulation((r)).
AB  - The etiopathogenesis of Carpal Tunnel Syndrome (CTS) is multifactorial and most
      cases are classified as idiopathic (Thurston 2013). A randomized controlled trial
      was performed to compare the effectiveness of Fascial Manipulation((r)) (FM) and
      Low-Level Laser Therapy (LLLT) for CTS. This prospective trial included 42
      patients (70 hands with symptoms) with clinical and electroneuromyographic
      diagnosis of CTS. The patients were randomly assigned to receive multiple
      sessions of FM or multiple session of LLLT. The Visual Analogic Scale (VAS) and
      Boston Carpal Tunnel Questionnaire (BCTQ) were performed at baseline, end of
      treatment and after three months. The group that received FM showed a significant
      reduction in subjective pain perception and an increased function assessed by
      BCTQ at the end of the treatment and follow-up. The group that received LLLT
      showed an improvement in the BCTQ at the end of the treatment but the improvement
      level was not sustained at the three month follow-up. FM is a valid alternative
      treatment for CTS. 

PMID- 25603751
TI  - Transmission of muscle force to fascia during exercise.
AB  - OBJECTIVE: As the muscle contracts, fibers get thicker, forcing the fascial
      tubular layers surrounding the muscle (endomysium, perimysium and epimysium) to
      expand in diameter and hence to shorten in length. We develop a mathematical
      model to determine the fraction of force generated by extremity muscles during
      contraction that is transmitted to the surrounding tubes of fascia. METHODS:
      Theory of elasticity is used to determine the modulus of elasticity, radial
      strain and the radial stress transmitted to the fascia. RESULTS: Starting with
      published data on dimensions of muscle and muscle force, we find radial stress is
      50% of longitudinal stress in the soleus, medial gastrocnemius, and elbow flexor
      and extensor muscles. CONCLUSION: Substantial stress is transmitted to fascia
      during muscular exercise, which has implications for exercise therapies if they
      are designed for fascial as well as muscular stress. This adds additional
      perspective to myofascial force transmission research.

PMID- 25603752
TI  - International Myopain Society (IMS) US chapter meeting.

PMID- 25603753
TI  - An evidence-informed review of the current myofascial pain literature--January
      2015.
AB  - This article provides an up-to-date review of the most recent publications about
      myofascial pain, trigger points (TrPs) and other related topics. We have added
      some commentaries where indicated with supporting references. In the Basic
      Research section, we reviewed the work by Danish researchers about the influence
      of latent TrPs and a second study of the presence and distribution of both active
      and latent TrPs in whiplash-associated disorders. The section on Soft Tissue
      Approaches considered multiple studies and case reports of the efficacy of
      myofascial release (MFR), classic and deep muscle massage, fascial techniques,
      and connective tissue massage. Dry needling (DN) is becoming a common approach
      and we included multiple studies, reviews, and case reports, while the section on
      Injection Techniques features an article on TrP injections following mastectomy
      and several articles about the utilization of botulinum toxin. Lastly, we review
      several articles on modalities and other clinical approaches. 

PMID- 25603755
TI  - Movement health.

PMID- 25603754
TI  - Effects of Baduanjin on mental health: a comprehensive review.
AB  - Mental disorders affect not only individual well-being but also community health,
      which pushes mental care professionals to investigate various solutions to
      accommodate different needs. The exercise of Baduanjin, a form of Qigong,
      facilitates improvements in psychological health, potentially serving as an
      alternative choice for interventions. This comprehensive review analyses 28
      publications, among which three are in English and 25 in Chinese, these
      indicating enhancement in quality of life and mental health for a variety of
      participants, including college students, middle-aged individuals, the elderly,
      and patients who suffer from different mental problems or chronic physical
      illnesses. The outcomes suggest that this cost-effective, learner-friendly and
      self-pacing exercise should be promoted in individual and group settings for both
      curative and preventive measures, and for which further investigations are also
      recommended. 

PMID- 25603756
TI  - Interrater reliability of a Pilates movement-based classification system.
AB  - OBJECTIVE: To determine the interrater reliability for identification of a
      specific movement pattern using a Pilates Classification system. METHOD: Videos
      of 5 subjects performing specific movement tasks were sent to raters trained in
      the DMA-CP classification system. RESULTS: Ninety-six raters completed the
      survey. Interrater reliability for the detection of a directional bias was
      excellent (Pi = 0.92, and K(free) = 0.89). Interrater reliability for classifying
      an individual into a specific subgroup was moderate (Pi = 0.64, K(free) = 0.55)
      however raters who had completed levels 1-4 of the DMA-CP training and reported
      using the assessment daily demonstrated excellent reliability (Pi = 0.89 and
      K(free) = 0.87). CONCLUSION: The reliability of the classification system
      demonstrated almost perfect agreement in determining the existence of a specific
      movement pattern and classifying into a subgroup for experienced raters. There
      was a trend for greater reliability associated with increased levels of training
      and experience of the raters.

PMID- 25603758
TI  - Abdominal training from a yoga perspective.

PMID- 25603757
TI  - Adherence to home exercises in non-specific low back pain. A randomised
      controlled pilot trial.
AB  - Specific exercises for the improvement of movement control of the lumbopelvic
      region are well-established for patients with non-specific low back pain (NSLBP)
      and movement control impairment (MCI). However, a lack of adherence to home
      exercise regimens is often observed. The aim of the study was to explore the
      differences in home exercise (HE) adherence between patients who perform
      conventional exercises and those who exercise with Augmented Feedback (AF).
      Twenty patients with NSLBP and MCI were randomly allocated into two groups. The
      physiotherapy group (PT group) completed conventional exercises, and the AF group
      exercised with an AF system that was designed for use in therapy settings. The
      main outcome measure was self-reported adherence to the home exercise regimen.
      There was no significant difference in HE duration between the groups (W = 64, p
      = 0.315). The AF group exercised for a median of 9 min and 4 s (IQR = 3'59"), and
      the PT group exercised for 4 min and 19 s (IQR = 8'30"). Exercising with AF led
      to HE times that were similar to those of conventional exercise, and AF might be
      used as an alternative therapy method for home exercise.

PMID- 25603759
TI  - [Syphilis in Assistance publique hospitals during World War I. Sanitary and
      patriotic implications].

PMID- 25603760
TI  - White matter microstructural changes in pure Alzheimer's disease and subcortical
      vascular dementia.
AB  - BACKGROUND AND PURPOSE: Recent studies have demonstrated that Alzheimer's disease
      (AD) and subcortical vascular dementia (SVaD) have white matter (WM)
      microstructural changes. However, previous studies on AD and SVaD rarely
      eliminated the confounding effects of patients with mixed Alzheimer's and
      cerebrovascular disease pathologies. Therefore, our aim was to evaluate the
      divergent topography of WM microstructural changes in patients with pure AD and
      SVaD. METHODS: Patients who were clinically diagnosed with AD and SVaD were
      prospectively recruited. Forty AD patients who were Pittsburgh compound B (PiB)
      positive [PiB(+) AD] without WM hyperintensities and 32 SVaD patients who were
      PiB negative [PiB(-) SVaD] were chosen. Fifty-six cognitively normal individuals
      were also recruited (NC). Tract-based spatial statistics of diffuse tensor
      imaging were used to compare patterns of fractional anisotropy (FA) and mean
      diffusivity (MD). RESULTS: Compared with the NC group, the PiB(+) AD group showed
      decreased FA in the bilateral frontal, temporal and parietal WM regions and the
      genu and splenium of the corpus callosum as well as increased MD in the left
      frontal and temporal WM region. PiB(-) SVaD patients showed decreased FA and
      increased MD in all WM regions. Direct comparison between PiB(+) AD and PiB(-)
      SVaD groups showed that the PiB(-) SVaD group had decreased FA across all WM
      regions and increased MD in all WM regions except occipital regions. CONCLUSION:
      Our findings suggest that pure AD and pure SVaD have divergent topography of WM
      microstructural changes including normal appearing WM.

PMID- 25603761
TI  - Serum Levels of 25-hydroxyvitamin D and Functional Outcome in Older Patients with
      Hip Fracture.
AB  - The aim was to assess prognostic value of serum 25-hydroxyvitamin D (25[OH] D)
      levels in older Chinese patients with hip fracture. From June, 2012 to February,
      2014, older patients with hip fracture were included. Serum 25(OH) D levels were
      measured at admission. The functional evaluation at the time of discharge was
      performed by the Barthel Index. In the 66 patients with an unfavorable outcome,
      serum 25(OH) D levels were lower compared with those with a favorable outcome. In
      multivariate analyses, there was an increased risk of unfavorable outcome
      associated with serum 25(OH) D levels <= 20 ng/ml (OR 5.25, 95% CI: 3.12-8.16).
      Our data supported an association between serum 25[OH] D levels at admission and
      short-term prognosis in Chinese older patients with hip fracture.

PMID- 25603762
TI  - Perinatal and maternal outcomes in planned home and obstetric unit births in
      women at 'higher risk' of complications: secondary analysis of the Birthplace
      national prospective cohort study.
AB  - OBJECTIVE: To explore and compare perinatal and maternal outcomes in women at
      'higher risk' of complications planning home versus obstetric unit (OU) birth.
      DESIGN: Prospective cohort study. SETTING: OUs and planned home births in
      England. POPULATION: 8180 'higher risk' women in the Birthplace cohort. METHODS:
      We used Poisson regression to calculate relative risks adjusted for maternal
      characteristics. Sensitivity analyses explored possible effects of differences in
      risk between groups and alternative outcome measures. MAIN OUTCOME MEASURES:
      Composite perinatal outcome measure encompassing 'intrapartum related mortality
      and morbidity' (intrapartum stillbirth, early neonatal death, neonatal
      encephalopathy, meconium aspiration syndrome, brachial plexus injury, fractured
      humerus or clavicle) and neonatal admission within 48 hours for more than 48
      hours. Two composite maternal outcome measures capturing intrapartum
      interventions/adverse maternal outcomes and straightforward birth. RESULTS: The
      risk of 'intrapartum related mortality and morbidity' or neonatal admission for
      more than 48 hours was lower in planned home births than planned OU births
      [adjusted relative risks (RR) 0.50, 95% CI 0.31-0.81]. Adjustment for clinical
      risk factors did not materially affect this finding. The direction of effect was
      reversed for the more restricted outcome measure 'intrapartum related mortality
      and morbidity' (RR adjusted for parity 1.92, 95% CI 0.97-3.80). Maternal
      interventions were lower in planned home births. CONCLUSIONS: The babies of
      'higher risk' women who plan birth in an OU appear more likely to be admitted to
      neonatal care than those whose mothers plan birth at home, but it is unclear if
      this reflects a real difference in morbidity. Rates of intrapartum related
      morbidity and mortality did not differ statistically significantly between
      settings at the 5% level but a larger study would be required to rule out a
      clinically important difference between the groups.

PMID- 25603763
TI  - Successful endovascular repair of exsanguinating penetrating carotid artery
      injury in two pediatric patients.
AB  - Immediate operative exploration has been considered mandatory for all penetrating
      injuries to Zone II of the neck and in any patient who is unstable, regardless of
      the location of the injury. We report two cases of penetrating carotid artery
      injuries in children successfully managed with endovascularly placed covered
      stents. These cases demonstrate that endovascular carotid artery repair can be
      considered in children, including in patients with Zone II injuries and in
      initially unstable patients.

PMID- 25603765
TI  - Rational molecular designs for drastic acceleration of the color-fading speed of
      photochromic naphthopyrans.
AB  - We report rational molecular designs for acceleration of the color-fading speed
      of photochromic 3H-naphthopyrans. By using steric and electrostatic repulsions
      induced by substituents at the 2- and 10-positions of 3H-naphthopyrans, the color
      fading speed accelerates from tens of minutes to microsecond time scales. The
      long-lived residual color, which is an important problem to be solved for
      industrial applications, can also be suppressed by these strategies. 

PMID- 25603764
TI  - Asymmetric conjugate additions and allylic alkylations using nucleophiles
      generated by hydro- or carbometallation.
AB  - This Minireview discusses catalytic asymmetric conjugate addition and allylic
      alkylation reactions where the nucleophiles were generated in situ by
      hydrometallation or carbometallation. This exciting recent trend in asymmetric
      catalysis promises to expand the range of transformations available for the rapid
      and selective assembly of complex, functional molecules for both academic and
      industrial research. This Minireview aims to serve as a reference for studies
      reported to date and discusses the current state-of-the-art, scope and
      limitations of these processes. 

PMID- 25603766
TI  - All the pain along with all the joy: spiritual resilience in lesbian and gay
      Christians.
AB  - Resilience among lesbian and gay (LG) Christians has received limited attention.
      We present results from a qualitative study of 27 LG Christians, for whom
      religion had high salience. The study explored the process of integrating sexual
      orientation with spirituality. Moving from recognition of incongruence between
      faith and sexual orientation to integration was found to be a resilience-building
      process. Through descriptive and process approaches, we identified three primary
      pathways individuals used to integrate their faith and sexual orientation:
      transforming theological meaning; finding a safe-enough congregation; and finding
      an affirming congregation. Some worked for social justice within congregations as
      part of the resilience-building process. We discuss important decision points for
      LG Christians that included critical evaluation of extant and potential support
      systems, redefining scripture and tradition, and transforming communities. A
      model for LG Christian Spiritual Resilience is presented. 

PMID- 25603767
TI  - A 12-year population-based study of freezing of gait in Parkinson's disease.
AB  - INTRODUCTION: Freezing of gait (FOG) is a potentially disabling motor problem in
      Parkinson's disease (PD) with uncertain etiology. Longitudinal studies of FOG in
      PD are scarce. We determined the prevalence, incidence, and associated clinical
      risk factors and concomitants of FOG during prospective long-term follow-up of a
      population-based PD cohort. METHODS: A community-based prevalent cohort of 232 PD
      patients was followed prospectively over 12 years. Reassessments were conducted
      at 4 and 8 years, and then annually. FOG, as well as severity of parkinsonism,
      motor complications, and psychotic symptoms were assessed by the Unified PD
      Rating Scale, and cognitive impairment by the Mini-Mental State Examination.
      Generalized estimating equations were applied to investigate baseline risk
      factors and concomitants of FOG over time. RESULTS: The point prevalence of FOG
      at baseline was 27% (95% confidence interval (95%-CI) 22-33%). By study end, 63%
      (95%-CI 56-69%) of patients had developed FOG. The incidence rate of FOG was
      124.2 (95%-CI 101.5-152.1) per 1000 person-years. Motor fluctuations (odds ratio
      (OR) 3.45; p = 0.036) and higher levodopa dose (OR 1.30/100 mg, p = 0.009) at
      baseline were independent risk factors of incident FOG. Prevalent FOG over time
      was additionally associated with features thought to reflect extrastrial, non
      dopaminergic pathologies, including PIGD (postural instability/gait difficulty,
      OR 6.30/10 points, p < 0.001) and psychosis (OR 1.85; p = 0.016). CONCLUSION:
      These findings demonstrate that FOG affects the majority of patients in the
      general PD population and provide support to the hypothesis that alterations in
      both basal ganglia and extrastriatal brain areas are involved in the pathogenesis
      of FOG in PD.

PMID- 25603769
TI  - Involuntary shoulder jerks after iatrogenic Thoraco-dorsal nerve injury.

PMID- 25603768
TI  - Head injury, potential interaction with genes, and risk for Parkinson's disease.
AB  - INTRODUCTION: To evaluate the association between head injury and Parkinson's
      disease (PD), focusing on the timing of head injury, and to explore potential
      interactions between head injury and genetic factors in PD etiology. METHODS: The
      analysis included 507 PD cases and 1330 controls, all non-Hispanic Whites. Head
      injury was retrospectively asked, and genotyping was performed mainly as part of
      a previous GWAS. RESULTS: We found a positive association between head injury and
      PD risk. Compared with no previous head injury, the odds ratio (OR) was 1.39 (95%
      confidence interval [CI]: 1.00, 1.94) for one and 2.33 (95% CI: 1.25, 4.35) for
      two or more head injuries (P for trend = 0.0016). We further found that the
      higher risk was largely attributed to head injuries before age 30. Compared with
      no previous head injury, the OR was 2.04 (95% CI: 1.33, 3.14) for head injury
      that occurred before age 18, 1.39 (95% CI: 0.81, 2.36) for head injury between
      ages 18-<30, and 1.04 (95% CI: 0.58, 1.87) for head injury that occurred at age
      30 or older (P for trend = 0.001). Exploratory interaction analyses showed a
      significant interaction between head injury and a SNP at the RBMS3 locus
      (rs10510622, uncorrected P = 0.0001). No interaction was found with GWAS tag SNPs
      at or near the MAPT, SNCA, LRRK2, and HLA loci. CONCLUSION: Our study suggests
      that head injury early in life may be an important risk factor for PD. The
      potential interaction with RBMS3 needs confirmation.

PMID- 25603770
TI  - Liver alkaline phosphatase: a missing link between choleresis and biliary
      inflammation.
AB  - Several lines of evidence show that serum alkaline phosphatase (AP) is not only a
      signpost of cholestasis but also a surrogate marker of the severity of primary
      biliary cirrhosis and primary sclerosing cholangitis. In the present opinion
      article, we review and discuss the putative role of liver AP in health and in
      cholestatic diseases. In inflammatory cholestatic conditions, loss of activity of
      liver AP (resulting from its relocation from canaliculi and the acidic milieu)
      might promote hyper-adenosine triphosphate-bilia, lipopolysaccharide overload,
      and subsequent exacerbation and perpetuation of inflammation. Drugs that can
      restore the polarity of hepatocytes and canalicular export of bile acids or act
      as bile alkalinity modifiers are predicted to exert anti-inflammatory effects and
      to benefit both primary biliary cirrhosis and primary sclerosing cholangitis.
      Oral administration of intestinal AP could be a valid therapeutic intervention
      that deserves further study under experimental conditions as well as in human
      diseases. Overall, the key role of the liver microenvironment that might shape
      the different facets of the inflammatory processes in fibrosing cholangiopathies
      is highlighted.

PMID- 25603771
TI  - A novel aqueous lithium-oxygen cell based on the oxygen-peroxide redox couple.
AB  - The electrochemical process of an aqueous Li-O2 cell is investigated. Li2O2 is
      detected as a discharge product of an aqueous Li-O2 cell using a catalyst-free
      carbon-based electrode. The electrolyte solution saturated with lithium hydroxide
      prevents hydrolysis of the Li2O2. Since the electron transfer process is based on
      the oxygen-peroxide redox couple, the galvanostatic charging-discharging profile
      shows stable cycling with an extremely low charging overpotential of <0.1 V at
      1.0 mA cm(-2). 

PMID- 25603773
TI  - Electrophysiological testing as a method of cone-rod and cone dystrophy diagnoses
      and prediction of disease progression.
AB  - PURPOSE: To determine the characteristics of patients with cone (CD) and cone-rod
      dystrophies (CRD) and to evaluate the changes in flash electroretinograms in both
      groups. METHODS: The retrospective study involved 48 patients-34 with CRD and 14
      with CD. The patients underwent full ophthalmological examination, including
      Goldmann perimetry and full-field flash electroretinogram (FERG) within the
      initial examination. These examinations were then repeated seven, or more, years
      later. The longest follow-up period was 10 years, with the mean at 8.2 years.
      During both examinations, we assessed the amplitudes of the b wave in the
      scotopic ERG test 0.01 (which reflects rod response), the maximal scotopic ERG
      test 3.0 (which reflects cone and rod response) and the photopic 3.0 ERG test
      (which reflects cone response). The results were then compared against normal
      values. RESULTS: The progression over time of ERG b wave amplitudes in the
      scotopic ERG 0.01, maximal scotopic ERG 3.0 and photopic ERG tests was assessed.
      There were significant differences in rod, maximal and cone responses, between CD
      and CRD patients. While rod responses were markedly decreased in CRD patients
      during their initial examination, the decrease in the rod function in both CD and
      CRD patients was similar in their follow-up examination (p = 0.2398). Moreover,
      during initial examination, maximal responses were less common amongst CRD
      patients, over those with CD. Following the observation period, patients
      suffering from CRD exhibited a significant decrease in both maximal (p = 0.0125)
      and cone (p = 0.0046) responses. CONCLUSION: The clinical course of CRD and CD
      may vary; however, the latter appears to have a more favourable course than
      former. Although, at initial examination, the cone function was more diminished
      in CD patients, the final examinations reveal a more significant drop for CRD
      patients. Consequently, a differential diagnosis is essential for treating
      patients and forecasting their disease progression.

PMID- 25603772
TI  - Protein kinase GCN2 mediates responses to glyphosate in Arabidopsis.
AB  - BACKGROUND: The increased selection pressure of the herbicide glyphosate has
      played a role in the evolution of glyphosate-resistance in weedy species, an
      issue that is becoming a threat to global agriculture. The molecular components
      involved in the cellular toxicity response to this herbicide at the expression
      level are still unidentified. RESULTS: In this study, we identify the protein
      kinase GCN2 as a cellular component that fosters the action of glyphosate in the
      model plant Arabidopsis thaliana. Comparative studies using wild-type and gcn2
      knock-out mutant seedlings show that the molecular programme that the plant
      deploys after the treatment with the herbicide, is compromised in gcn2. Moreover,
      gcn2 adult plants show a lower inhibition of photosynthesis, and both seedlings
      and adult gcn2 plants accumulate less shikimic acid than wild-type after
      treatment with glyphosate. CONCLUSIONS: These results points to an unknown GCN2
      dependent factor involved in the cascade of events triggered by glyphosate in
      plants. Data suggest either that the herbicide does not equally reach the target
      enzyme in a gcn2 background, or that a decreased flux in the shikimate pathway in
      a gcn2 plants minimize the impact of enzyme inhibition.

PMID- 25603774
TI  - Characteristics and trends of POBA in current DES Era.
AB  - The aim of this study is to clarify the characteristics and trends of POBA in
      current drug-eluting stent (DES) era. We examined retrospectively the cases of
      POBA performed in our institute during the years from 2008 to 2012. For control,
      bare metal stents (BMS) and DES implantation done in 2011 were analyzed. During
      the period, 85 cases of POBA, 63 BMS and 132 DES were identified. In the result,
      the rate of restenosis in POBA was significantly higher than BMS and DES (39.7,
      14.9, 3.7%, POBA, BMS, DES, respectively, p < 0.001). We assumed three categories
      depending on the reasons for selecting POBA. (1) Stent delivery failure or
      expected difficulty of stent delivery due to calcification, etc. (n = 14), (2)
      intervention for in-stent restenosis or stent thrombosis (n = 34), (3) successful
      POBA applied to small vessels without complication (n = 14). According to it,
      category 1 showed significantly high probability of restenosis compared with
      others [(1) 10/14, 71.4%, (2) 12/34, 35.3%, 3; 2/14, 14.3%, p < 0.05]. In
      addition, category 3 showed nearly as good as BMS. Balloons used in POBA
      contained 32 non-compliant balloons and 14 scoring balloons, whereas 30 were semi
      compliant balloons only. ACC/AHA lesion type B2/C was 85.7, 45.7 and 50.0%, and
      cases treated only with semi-compliant balloon were 57.1, 14.3, 92.9% (category
      (1), (2) and (3), respectively, both p < 0.05). Therefore, this fact shows that a
      case of small vessel of which diameter is less than 2.5 mm would have a favorable
      outcome with POBA when treated well only with semi-compliant balloon under the
      current DES era.

PMID- 25603775
TI  - The prognostic significance of stable disease following high-dose interleukin-2
      (IL-2) treatment in patients with metastatic melanoma and renal cell carcinoma.
AB  - High-dose interleukin-2 (HD IL-2) is an approved immunotherapy agent for
      metastatic melanoma and renal cell carcinoma resulting in objective responses in
      15-20 % of patients. An additional subset of patients achieves stable disease,
      and the natural history of these patients has not been well documented. We
      hypothesized that stable disease following HD IL-2 is associated with a survival
      advantage. To explore this hypothesis, a retrospective chart review of 305
      patients diagnosed with metastatic melanoma or renal cell carcinoma treated with
      HD IL-2 was conducted. Patient characteristics, response based on standard RECIST
      criteria and overall survival were analyzed using the Kaplan-Meier method and
      associations with clinical response were compared using a log-rank test. Two
      hundred and forty-five patients had melanoma and 60 had renal cell carcinoma. Of
      these, 217 had complete data available for analysis. Fifty-nine percentage had
      progressive disease (PD), 26 % had stable disease (SD) and 15 % had an objective
      complete (CR) or partial response (PR). Median overall survival was 16.8 months
      for all patients with available survival data; patients with PD had a median
      survival of 7.9 months compared to 38.2 months for stable disease, while the
      median has not been reached for those with objective responses. This
      retrospective data support an association between overall survival and stable
      disease, suggesting that clinical benefit may be underestimated for patients
      treated with HD IL-2. The data further support the use of disease control rate
      (CR + PR + SD) as a more meaningful endpoint for future clinical studies of tumor
      immunotherapy, including future studies of HD IL-2.

PMID- 25603776
TI  - Blockade of intracellular Zn2+ signaling in the dentate gyrus erases recognition
      memory via impairment of maintained LTP.
AB  - There is no evidence on the precise role of synaptic Zn2+ signaling on the
      retention and recall of recognition memory. On the basis of the findings that
      intracellular Zn2+ signaling in the dentate gyrus is required for object
      recognition, short-term memory, the present study deals with the effect of
      spatiotemporally blocking Zn2+ signaling in the dentate gyrus after LTP induction
      and learning. Three-day-maintained LTP was impaired 1 day after injection of
      clioquinol into the dentate gyrus, which transiently reduced intracellular Zn2+
      signaling in the dentate gyrus. The irreversible impairment was rescued not only
      by co-injection of ZnCl2 , which ameliorated the loss of Zn2+ signaling, but also
      by pre-injection of Jasplakinolide, a stabilizer of F-actin, prior to clioquinol
      injection. Simultaneously, 3-day-old space recognition memory was impaired 1 day
      after injection of clioquinol into the dentate gyrus, but not by pre-injection of
      Jasplakinolide. Jasplakinolide also rescued both impairments of 3-day-maintained
      LTP and 3-day-old memory after injection of ZnAF-2DA into the dentate gyrus,
      which blocked intracellular Zn2+ signaling in the dentate gyrus. The present
      paper indicates that the blockade and/or loss of intracellular Zn2+ signaling in
      the dentate gyrus coincidently impair maintained LTP and recognition memory. The
      mechanism maintaining LTP via intracellular Zn2+ signaling in dentate granule
      cells, which may be involved in the formation of F-actin, may retain space
      recognition memory.

PMID- 25603778
TI  - Iron-catalyzed hydrogenation of bicarbonates and carbon dioxide to formates.
AB  - The catalytic hydrogenation of carbon dioxide and bicarbonate to formate has been
      explored extensively. The vast majority of the known active catalyst systems are
      based on precious metals. Herein, we describe an effective, phosphine-free, air-
      and moisture-tolerant catalyst system based on Knolker's iron complex for the
      hydrogenation of bicarbonate and carbon dioxide to formate. The catalyst system
      can hydrogenate bicarbonate at remarkably low hydrogen pressures (1-5 bar). 

PMID- 25603777
TI  - Effect of cycling in the heat for 164 km on procoagulant and fibrinolytic
      parameters.
AB  - PURPOSE: We assessed the impact of completing the Hotter'n Hell Hundred (HHH), an
      annual 164 km road cycling event performed in a hot environment, on hemostatic
      balance in men. METHODS: Sixteen men who completed the ride in <6 h were included
      in this study. Plasma samples were collected on that morning of the ride (PRE)
      and immediately on the completion of the ride (IP). Primary hemostasis was
      assessed by platelet count and von Willebrand factor antigen (vWF:Ag).
      Coagulation was assessed by measuring prothrombin fragment 1 + 2 (PTF 1 + 2) and
      thrombin-antithrombin complex (TAT), whereas fibrinolysis was assessed by
      plasminogen activator inhibitor antigen (PAI-1 Ag), tissue plasminogen activator
      (tPA Ag), and D-Dimer analyses. RESULTS: Compared to PRE, increases (p < 0.001)
      were observed at IP for platelets (39 %), vWF:Ag (65 %), PTF 1 + 2 (47 %), TAT
      (81 %), tPA Ag (231 %), PAI-1 Ag (148 %), and D-Dimer (54 %). PRE PAI-1 Ag
      concentrations were directly related to BMI and waist circumference (p < 0.05). D
      Dimer concentrations at IP correlated positively with age (p < 0.05).
      CONCLUSIONS: Completing the HHH activated the coagulation and fibrinolytic
      systems in balance. Age was positively correlated with IP D-Dimer concentrations.
      Additionally, participants displaying a larger BMI and waist circumference
      exhibited a positive correlation with PRE PAI-1 Ag concentrations.

PMID- 25603780
TI  - Image artifacts in single molecule localization microscopy: why optimization of
      sample preparation protocols matters.
AB  - Single molecule localization microscopy (SMLM) techniques allow for sub
      diffraction imaging with spatial resolutions better than 10 nm reported. Much has
      been discussed relating to different variations of SMLM and all-inclusive
      microscopes can now be purchased, removing the need for in-house software or
      hardware development. However, little discussion has occurred examining the
      reliability and quality of the images being produced, as well as the potential
      for overlooked preparative artifacts. As a result of the up to an order-of
      magnitude improvement in spatial resolution, substantially more detail is
      observed, including changes in distribution and ultrastructure caused by the many
      steps required to fix, permeabilize, and stain a sample. Here we systematically
      investigate many of these steps including different fixatives, fixative
      concentration, permeabilization concentration and timing, antibody concentration,
      and buffering. We present three well-optimized fixation protocols for staining
      microtubules, mitochondria and actin in a mammalian cell line and then discuss
      various artifacts in relation to images obtained from samples prepared using the
      protocols. The potential for such errors to go undetected in SMLM images and the
      complications in defining a 'good' image using previous parameters applied to
      confocal microscopy are also discussed. 

PMID- 25603781
TI  - 2,2'-Bis(monoacylglycero) PO4 (BMP), but Not 3,1'-BMP, increases membrane
      curvature stress to enhance alpha-tocopherol transfer protein binding to
      membranes.
AB  - Previous work revealed that alpha-tocopherol transfer protein (alpha-TTP) co
      localizes with bis(monoacylglycero)phosphate (BMP) in late endosomes. BMP is a
      lipid unique to late endosomes and is believed to induce membrane curvature and
      support the multivesicular nature of this organelle. We examined the effect of
      BMP on alpha-TTP binding to membranes using dual polarization interferometry and
      vesicle-binding assay. alpha-TTP binding to membranes is increased by the
      curvature-inducing lipid BMP. alpha-TTP binds to membranes with greater affinity
      when they contain the 2,2'-BMP versus 3,1'-BMP isomers. 

PMID- 25603783
TI  - Diffuse lung disease in infants less than 1 year of age: Histopathological
      diagnoses and clinical outcome.
AB  - INTRODUCTION: Interstitial lung disease (ILD) in infants is rare. Clinical and
      radiological features are often non-specific, and overlap with growth disorders
      and infection. In infants with severe respiratory compromise, lung biopsy is
      often necessary to guide acute management, but the risk and diagnostic yield of
      this procedure is incompletely understood. AIMS: To retrospectively review
      infants undergoing open lung biopsy for suspected ILD at a large referral center;
      to determine morbidity and mortality related to the procedure; and to describe
      subsequent diagnosis and outcome. METHODS: Lung biopsies performed in infants
      (aged <1 year) between January 1, 2005 and March 31, 2012 were identified and
      clinical data were collected. Biopsies were reclassified using the ChILD
      classification for diffuse lung disorders in infants. RESULTS: Twenty-seven
      infants were identified, with the number of biopsies performed increasing each
      year over the study period. There was no mortality and negligible morbidity
      associated with biopsy. Diagnoses seen were similar to those reported by the
      ChILD network. Histopathological diagnosis was not compatible with life in the
      absence of lung transplant in 6/27 (22%) of infants. Of the 14 children
      longitudinally followed up (median 0.5 (0.4 - 5.81) years), only four continued
      to require supplemental oxygen. CONCLUSION: Lung biopsy in infants with suspected
      ILD is safe, and histopathological diagnosis frequently assists treatment
      decisions, particularly with regard to withdrawal of care.

PMID- 25603782
TI  - Molecular underpinnings of ventral surface chemoreceptor function: focus on KCNQ
      channels.
AB  - Central chemoreception is the mechanism by which CO2/H(+) -sensitive neurons
      (i.e. chemoreceptors) regulate breathing in response to changes in tissue
      CO2/H(+) . Neurons in the retrotrapezoid nucleus (RTN) directly regulate
      breathing in response to changes in tissue CO2/H(+) and function as a key locus
      of respiratory control by integrating information from several respiratory
      centres, including the medullary raphe. Therefore, chemosensitive RTN neurons
      appear to be critically important for maintaining breathing, thus understanding
      molecular mechanisms that regulate RTN chemoreceptor function may identify
      therapeutic targets for the treatment of respiratory control disorders. We have
      recently shown that KCNQ (Kv7) channels in the RTN are essential determinants of
      spontaneous activity ex vivo, and downstream effectors for serotonergic
      modulation of breathing. Considering that loss of function mutations in KCNQ
      channels can cause certain types of epilepsy including those associated with
      sudden unexplained death in epilepsy (SUDEP), we propose that dysfunctions of
      KCNQ channels may be one cause for epilepsy and respiratory problems associated
      with SUDEP. In this review, we will summarize the role of KCNQ channels in the
      regulation of RTN chemoreceptor function, and suggest that these channels
      represent useful therapeutic targets for the treatment of respiratory control
      disorders.

PMID- 25603784
TI  - Classification of additives for organic photovoltaic devices.
AB  - The use of additives to improve the performance of organic photovoltaic cells has
      been intensely researched in recent years. However, so far, no system has been
      reported for the classification of additives and their functions. In this report,
      a system for classifying additives according to the fundamental mechanism by
      which they influence microstructure formation for P3HT:PCBM is suggested. The
      major parameters used for their classification are solubility and drying
      kinetics. Both are discussed in detail and their consequences on processing are
      analyzed. Furthermore, a general mechanism to classify the impact of additives on
      structure formation is suggested and discussed for different materials relevant
      to organic photovoltaic devices. 

PMID- 25603786
TI  - Hemostatic potential of latex proteases from Tabernaemontana divaricata (L.) R.
      Br. ex. Roem. and Schult. and Artocarpus altilis (Parkinson ex. F.A. Zorn)
      Forsberg.
AB  - Pharmacological properties exhibited by latex of plants are due to various
      biologically active compounds including several proteolytic enzymes. Present
      study evaluates hemostatic potential of Tabernaemontana divaricata and Artocarpus
      altilis from Apocynaceae and Moraceae families respectively. The latex of these
      plants were initially subjected to dialysis and crude extracts were estimated for
      proteolytic activity using casein as the substrate. Mean caseinolytic activity
      for 100 MUg of latex protein was found to be 56.16 +/- 0.57 and 45 +/- 0.3 U/h
      for T. divaricata and A. altilis respectively. Caseinolytic activity by both the
      plant extracts was higher than standard proteases, papain and trypsin. However
      the difference was significant (p < 0.05) with papain alone. Crude enzymes (CE)
      from both plants exhibited coagulant activity on human platelet poor plasma by
      recalcification time. A significant reduction in clotting time was exhibited by
      T. divaricata compared to A. altilis (p < 0.05). These results were further
      substantiated with fibrinogen agarose plate assay. Crude enzyme of both plants
      also hydrolyzed blood clot. Mean % of thrombolysis by T. divaricata was 80.75 +/-
      1.2 and that of A. altilis was 70.24 +/- 1.52. Inhibition studies confirmed
      cysteine protease nature of CE. Comparative analysis revealed T. divaricata to be
      the best among the two for its hemostatic potential. This study scientifically
      validates the use of latex from these plants in the management of fresh cuts or
      wounds. 

PMID- 25603785
TI  - Trends in breast biopsy pathology diagnoses among women undergoing mammography in
      the United States: a report from the Breast Cancer Surveillance Consortium.
AB  - BACKGROUND: Current data on the pathologic diagnoses of breast biopsy after
      mammography can inform patients, clinicians, and researchers about important
      population trends. METHODS: Breast Cancer Surveillance Consortium data on
      4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology
      specimens. Trends in diagnoses in biopsies by time and risk factors (patient age,
      breast density, and family history of breast cancer) were examined for screening
      and diagnostic mammography (performed for a breast symptom or short-interval
      follow-up). RESULTS: Of the total mammograms, 88.5% were screening and 11.5%
      diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by
      biopsies. The frequency of biopsies over time was stable after screening
      mammograms, but increased after diagnostic mammograms. For biopsies obtained
      after screening, frequencies of invasive carcinoma increased over time for women
      ages 40-49 and 60-69, Ductal carcinoma in situ (DCIS) increased for those ages 40
      69, whereas benign diagnoses decreased for all ages. No trends in pathology
      diagnoses were found following diagnostic mammograms. Dense breast tissue was
      associated with high-risk lesions and DCIS relative to nondense breast tissue.
      Family history of breast cancer was associated with DCIS and invasive cancer.
      CONCLUSIONS: Although the frequency of breast biopsy after screening mammography
      has not changed over time, the percentages of biopsies with DCIS and invasive
      cancer diagnoses have increased. Among biopsies following mammography, women with
      dense breasts or family history of breast cancer were more likely to have high
      risk lesions or invasive cancer. These findings are relevant to breast cancer
      screening and diagnostic practices.

PMID- 25603787
TI  - Bovine sperm plasma membrane proteomics through biotinylation and subcellular
      enrichment.
AB  - A significant proportion of mammalian fertilization is mediated through the
      proteomic composition of the sperm surface. These protein constituents can
      present as biomarkers to control and regulate breeding of agricultural animals.
      Previous studies have addressed the bovine sperm cell apical plasma membrane (PM)
      proteome with nitrogen cavitation enrichment. Alternative workflows would enable
      to expand the compositional data more globally around the entire sperm's surface.
      We used a cell surface biotin-labeling in combination with differential
      centrifugation to enrich sperm surface proteins. Using nano-LC MS/MS, 338
      proteins were confidently identified in the PM-enriched proteome. Functional
      categories of sperm-egg interaction, protein turnover, metabolism as well as
      molecular transport, spermatogenesis, and signal transduction were represented by
      proteins with high quantitative signal in our study. A highly significant degree
      of enrichment was found for transmembrane and PM-targeted proteins. Among them,
      we also report proteins previously not described on bovine sperm (CPQ, CD58,
      CKLF, CPVL, GLB1L3, and LPCAT2B) of which CPQ and CPVL cell surface localization
      was further validated. A descriptive overview of the bovine sperm PM integral and
      peripheral proteins is provided to complement future studies on animal
      reproduction and its relation to sperm cell surface. All MS data have been
      deposited in the ProteomeXchange with identifier PXD001096
      (http://proteomecentral.proteomexchange.org/dataset/PXD001096). 

PMID- 25603788
TI  - The effect of a rapid response team on resident perceptions of education and
      autonomy.
AB  - BACKGROUND: The impact of rapid response teams (RRTs) on resident physicians'
      education and clinical autonomy is not well described. OBJECTIVE: To determine
      whether resident physicians perceive educational benefit from collaboration with
      an RRT and whether they believe that the RRT adversely affects their clinical
      autonomy. DESIGN: Survey study. METHODS: Study subjects were asked to participate
      in a brief online survey. The survey contained 7 demographic items and 20 RRT
      related items graded on a 5-point Likert scale ranging from strongly disagree to
      strongly agree. SETTING/SUBJECTS: The study was conducted at a tertiary care
      academic medical center. Subjects included all residents in specialties involving
      direct patient care and the potential to use the adult RRT. RESULTS: The response
      rate was 72%; 35% of respondents were interns, and 69% were in medical fields.
      Residents agreed that working with the RRT is a valuable educational experience
      (78%) and disagreed that the RRT decreased their clinical autonomy (76%).
      Surgical residents were less likely than medical residents to perceive
      educational value from RRT interactions (P = 0.01) or to report collaborative
      decision making with the RRT (P = 0.04). CONCLUSIONS: The majority of resident
      physicians perceive educational benefit from interaction with the RRT, though
      this benefit is greater for less experienced residents and for those residents
      who routinely provide care for critically ill patients and serve as code team
      leaders. Few residents, irrespective of years of training or specialty, felt that
      the RRT reduced their clinical autonomy.

PMID- 25603789
TI  - Factors associated with medication warning acceptance for hospitalized adults.
AB  - BACKGROUND: Computerized provider order entry (CPOE) systems can warn clinicians
      ordering medications about potential allergic or adverse reactions, duplicate
      therapy, and interactions with other medications. Clinicians frequently override
      these warnings. Understanding the factors associated with warning acceptance
      should guide revisions to these systems. OBJECTIVE: Increase understanding of the
      factors associated with medication warning acceptance. DESIGN: Retrospective
      study of all single-medication warnings generated in a CPOE system from October
      2009 through April 2010. SETTING: Academic medical center. PATIENTS: All adult
      non-intensive care unit patients hospitalized during the study period. RESULTS: A
      total of 40,391 medication orders generated a single-medication warning during
      the 7-month study period. Of these warnings, 47% were duplicate warnings, 47%
      interaction warnings, 6% allergy warnings, 0.1% adverse reaction warnings, and
      9.8% were repeated for the same patient, medication, and provider. Only 4% of
      warnings were accepted. In multivariate analysis, warning acceptance was
      positively associated with male patient gender, admission to a service other than
      internal medicine, caregiver status other than resident, parenteral medications,
      lower numbers of warnings, and allergy or adverse reaction warning types. Older
      patient age, longer length of stay, inclusion on the Institute for Safe
      Medication Practice's List of High Alert Medications, and interaction warning
      type were all negatively associated with warning acceptance. CONCLUSIONS:
      Medication warnings are rarely accepted. Acceptance is more likely when the
      warning is infrequently encountered, and least likely when it is potentially most
      important. Warning systems should be redesigned to increase their effectiveness
      for the sickest patients, the least experienced physicians, and the medications
      with the greatest potential to cause harm.

PMID- 25603790
TI  - Improving appropriateness of acid-suppressive medication use via computerized
      clinical decision support.
AB  - As part of the Choosing Wisely Campaign, the Society of Hospital Medicine
      identified reducing inappropriate use of acid-suppressive medication for stress
      ulcer prophylaxis as 1 of 5 key opportunities to improve the value of care for
      hospitalized patients. We designed a computerized clinical decision support
      intervention to reduce use of acid-suppressive medication for stress ulcer
      prophylaxis in hospitalized patients outside of the intensive care unit at an
      academic medical center. Using quasiexperimental interrupted time series
      analysis, we found that the decision support intervention resulted in a
      significant reduction in use of acid-suppressive medication with stress ulcer
      prophylaxis selected as the only indication, a nonsignificant reduction in
      overall use, and no change in use on discharge. We found low rates of use of acid
      suppressive medication for the purpose of stress ulcer prophylaxis even before
      the intervention, and continuing preadmission medication was the most commonly
      selected indication throughout the study. Our results suggest that attention
      should be focused on both the inpatient and outpatient settings when designing
      future initiatives to improve the appropriateness of acid-suppressive medication
      use.

PMID- 25603791
TI  - Clinical decision support: a tool of the hospital trade.

PMID- 25603792
TI  - Rapid response teams in teaching hospitals: aligning efforts to improve medical
      education and quality.

PMID- 25603793
TI  - Photoswitching kinetics and phase-sensitive detection add discriminative
      dimensions for selective fluorescence imaging.
AB  - Non-invasive separation-free protocols are attractive for analyzing complex
      mixtures. To increase selectivity, an analysis under kinetic control, through
      exploitation of the photochemical reactivity of labeling contrast agents, is
      described. The simple protocol is applied in optical fluorescence microscopy,
      where autofluorescence, light scattering, as well as spectral crowding presents
      limitations. Introduced herein is OPIOM (out-of-phase imaging after optical
      modulation), which exploits the rich kinetic signature of a photoswitching
      fluorescent probe to increase selectively and quantitatively its contrast.
      Filtering the specific contribution of the probe only requires phase-sensitive
      detection upon matching the photoswitching dynamics of the probe and the
      intensity and frequency of a modulated monochromatic light excitation. After in
      vitro validation, we applied OPIOM for selective imaging in mammalian cells and
      zebrafish, thus opening attractive perspectives for multiplexed observations in
      biological samples.

PMID- 25603794
TI  - Uptake and characteristics of zoledronic acid and denosumab patients and
      physicians in Ontario, Canada: impact of drug formulary access.
AB  - The addition of Limited Use criteria (less restrictive access) for zoledronic
      acid resulted in an immediate and significant increase in uptake and resulted in
      differences in patient/physician characteristics. In comparison, the uptake of
      denosumab (only listed with Limited Use) was rapid. Thus, formulary access
      restrictions have significant implications for prescribing. INTRODUCTION: We
      sought to describe the use of zoledronic acid and denosumab by physicians and
      patients over time and examine the impact of a 2012 provincial formulary
      modification that removed the administrative burden on physicians when
      prescribing zoledronic acid. METHODS: We identified users of zoledronic acid and
      denosumab using Ontario pharmacy claims data. The number of new patients and
      physicians was plotted and examined over time. Interrupted time series analysis
      examined the impact of a formulary modification to zoledronic acid use and
      prescribing. Descriptive characteristics of patients and prescribers were
      summarized pre- and post-formulary modification for zoledronic acid and overall
      for denosumab. RESULTS: We identified 1463 zoledronic acid patients treated by
      627 physicians and 16,736 denosumab patients treated by 2904 physicians. In the
      first 2 months on the market, we identified a rapid uptake of denosumab (>450
      physicians and >1200 patients) in contrast to zoledronic acid (<10 physicians and
      <10 patients). Zoledronic acid use increased significantly in the 2-month post
      formulary change, yet no change in denosumab was observed. Prior to the formulary
      modification, more zoledronic acid patients had a history of osteoporosis therapy
      (41 vs. 26%) or bone density testing (30 vs. 10%). Compared to zoledronic
      patients (post-formulary modification), more denosumab patients had prior
      osteoporosis therapy (55 vs. 26%), yet fewer had a gastrointestinal diagnosis (6
      vs. 11%). CONCLUSION: We identified a rapid uptake of denosumab in only 15 months
      of observation. A provincial formulary modification to zoledronic acid resulted
      in an increase in utilization and impacted patient characteristics.

PMID- 25603795
TI  - The effects of differing resistance training modes on the preservation of bone
      mineral density in postmenopausal women: a meta-analysis.
AB  - This meta-analysis synthesized current evidence from 24 clinical trials to
      evaluate the impact of different resistance training modes on postmenopausal bone
      loss. Exercise interventions were categorized into two training modes, namely
      resistance-alone versus combined resistance training protocols. The combined
      resistance training protocols were defined as the combination of resistance
      training and high-impact or weight-bearing exercise. The results suggested that
      the combined resistance training protocols were effective in improving bone
      mineral density (BMD) at the femoral neck and lumbar spine. INTRODUCTION: The
      current meta-analysis aimed to examine the effects of combined resistance and
      resistance-alone training protocols on the preservation of femoral neck and
      lumbar spine BMD in postmenopausal women. METHODS: An electronic database search
      was conducted in PubMed, EMBASE, SPORTDiscus, Web of Science, and ProQuest up to
      March 1, 2014 for the influence of resistance exercise on BMD in postmenopausal
      women. The study quality was evaluated. The effect sizes were estimated in terms
      of the standardized mean difference (SMD). A subgroup analysis was conducted by
      exercise categories. RESULTS: Twenty-four studies were included in the overall
      analysis of skeletal response to resistance exercise. The between-study
      heterogeneity was evident for the hip (I (2) = 46.5%) and spine (I (2) = 62.3%).
      The overall analysis suggested that resistance training significantly increased
      femoral neck BMD (SMD = 0.303, 95% confidence interval (95% CI) = 0.127-0.479, p
      = 0.001) and lumbar spine BMD (SMD = 0.311, 95% CI = 0.115-0.507, p = 0.002) in
      postmenopausal women. However, subgroup analysis indicated that combined
      resistance training programs significantly affected both the hip BMD (SMD =
      0.411, 95% CI = 0.176-0.645, p = 0.001) and spine BMD (SMD = 0.431, 95% CI =
      0.159-0.702, p = 0.002), whereas resistance-alone protocols only produced
      nonsignificant positive effects both on the femoral neck and lumbar spine BMD.
      CONCLUSIONS: Combined resistance exercise protocols appear effective in
      preserving femoral neck and lumbar spine BMD in postmenopausal women, whereas
      resistance-alone protocols only produced a nonsignificant positive effect.

PMID- 25603796
TI  - Cell type-specific gene expression profiling in brain tissue: comparison between
      TRAP, LCM and RNA-seq.
AB  - The brain is an organ that consists of various cell types. As our knowledge of
      the structure and function of the brain progresses, cell type-specific research
      is gaining importance. Together with advances in sequencing technology and
      bioinformatics, cell type-specific transcriptome studies are providing important
      insights into brain cell function. In this review, we discuss 3 different cell
      type-specific transcriptome analyses i.e., Laser Capture Microdissection (LCM),
      Translating Ribosome Affinity Purification (TRAP)/RiboTag, and single cell RNA
      Seq, that are widely used in the field of neuroscience.

PMID- 25603797
TI  - MicroRNAs: promising biomarkers for diagnosis and therapeutic targets in human
      colorectal cancer metastasis.
AB  - Colorectal cancer (CRC) is the third most common cancer and the fourth most
      common cause of cancer-related death worldwide. Distant metastasis is a major
      cause of mortality in CRC. MicroRNAs (miRNAs) are small non-coding RNA molecules
      involved in the post-transcriptional and translational regulation of gene
      expression. Many miRNAs are aberrantly expressed in cancer and influence tumor
      progression. Accumulating studies suggest that multiple miRNAs are actively
      involved in the CRC metastasis process. Thus, we aim to introduce the role of
      miRNAs in multi-steps of CRC metastasis, including cancer cell invasion,
      intravasation, circulation, extravasation, colonization, angiogenesis, and
      epithelial-mesenchymal transition (EMT). Moreover, we suggest the potential
      application of miRNAs as biomarkers for CRC patients with metastasis.

PMID- 25603798
TI  - Diet Quality and Physical Activity Outcome Improvements Resulting From a Church
      Based Diet and Supervised Physical Activity Intervention for Rural, Southern,
      African American Adults: Delta Body and Soul III.
AB  - We assessed the effects of a 6-month, church-based, diet and supervised physical
      activity intervention, conducted between 2011 and 2012, on improving diet quality
      and increasing physical activity of Southern, African American adults. Using a
      quasi-experimental design, eight self-selected, eligible churches were assigned
      to intervention or control. Assessments included dietary, physical activity,
      anthropometric, and clinical measures. Mixed model regression analysis and
      McNemar's test were used to determine if within and between group differences
      were significant. Cohen's d effect sizes for selected outcomes also were computed
      and compared with an earlier, lower dose intervention. Retention rates were 84%
      (102/122) for control and 76% (219/287) for intervention participants. Diet
      quality components, including fruits, vegetables, discretionary calories, and
      total quality, improved significantly in the intervention group.
      Strength/flexibility physical activity also increased in the intervention group,
      while both aerobic and strength/flexibility physical activity significantly
      decreased in the control group. Effect sizes for selected health outcomes were
      larger in the current intervention as compared to an earlier, less intense
      iteration of the study. Results suggest that more frequent education sessions as
      well as supervised group physical activity may be key components to increasing
      the efficacy of behavioral lifestyle interventions in rural, Southern, African
      American adults. 

PMID- 25603800
TI  - Transient neonatal hyperthyrotropinemia is a risk factor for developing
      persistent hyperthyrotropinemia in childhood with repercussion on developmental
      status.
AB  - OBJECTIVE: Transient neonatal hyperthyrotropinemia (TNH) is defined as a neonatal
      abnormality of thyroid function, which reverts to normal at re-examination after
      2 weeks of life. The thyroid function of these infants has not been sufficiently
      studied in terms of the risk of developing persistent hyperthyrotropinemia (PH)
      in later childhood and its impact on growth and development. DESIGN: A
      prospective cohort study included all babies born in our hospital between 2001
      and 2006 and screened for hypothyroidism, whose thyroid function was re-examined
      6 years later. Exclusion criteria included the following conditions: preterm
      birth, birth weight <2500 g, Down's syndrome, descendants of mothers with immune
      thyroid disease, congenital malformations, cardiac, renal, hepatic, and metabolic
      diseases, and steroid or dopamine medication. The variables included are TSH and
      thyroxine at neonatal screening and 6 years later. Main outcomes are the risk of
      developing PH in childhood, linear growth, and development using Parents'
      Evaluation of Developmental Status (PEDS). RESULTS: Out of 5040 normal-term
      newborns, 301 (6.0%, 95% CI 5.3-6.6%) have TSH >=10 mU/l (TNH). Six years later,
      we re-examined 65 randomly selected children with TNH and 185 controls. In the
      TNH cohort, we found six out of 65 children (9.2%, 95% CI 1.4-17.0%) with PH (TSH
      >=6.4 mU/l), and three out of 185 (1.6%, 95% CI 0.3-4.7%) among controls,
      relative risk 5.7 (95% CI 1.5-22.1), P=0.0114. TSH and developmental delay were
      found to be significantly higher in the TNH cohort (4.7+/-1.3 mU/l vs 2.1+/-0.5
      mU/l, P<0.0001 and 15/65 (23%, 95% CI 12-34.1) vs 21/185 (11.3%, 95% CI 6.5-16.2)
      P=0.0348). CONCLUSIONS: Newborns with TNH have a higher risk of developing PH in
      childhood, with repercussion on developmental status.

PMID- 25603799
TI  - A role for Ras in inhibiting circular foraging behavior as revealed by a new
      method for time and cell-specific RNAi.
AB  - BACKGROUND: The nematode worm Caenorhabditis elegans, in which loss-of-function
      mutants and RNA interference (RNAi) models are available, is a model organism
      useful for analyzing effects of genes on various life phenomena, including
      behavior. In particular, RNAi is a powerful tool that enables time- or cell
      specific knockdown via heat shock-inducible RNAi or cell-specific RNAi. However,
      conventional RNAi is insufficient for investigating pleiotropic genes with
      various sites of action and life stage-dependent functions. RESULTS: Here, we
      investigated the Ras gene for its role in exploratory behavior in C. elegans. We
      found that, under poor environmental conditions, mutations in the Ras-MAPK
      signaling pathway lead to circular locomotion instead of normal exploratory
      foraging. Spontaneous foraging is regulated by a neural circuit composed of three
      classes of neurons: IL1, OLQ, and RMD, and we found that Ras functions in this
      neural circuit to modulate the direction of locomotion. We further observed that
      Ras plays an essential role in the regulation of GLR-1 glutamate receptor
      localization in RMD neurons. To investigate the temporal- and cell-specific
      profiles of the functions of Ras, we developed a new RNAi method that enables
      simultaneous time- and cell-specific knockdown. In this method, one RNA strand is
      expressed by a cell-specific promoter and the other by a heat shock promoter,
      resulting in only expression of double-stranded RNA in the target cell when heat
      shock is induced. This technique revealed that control of GLR-1 localization in
      RMD neurons requires Ras at the adult stage. Further, we demonstrated the
      application of this method to other genes. CONCLUSIONS: We have established a new
      RNAi method that performs simultaneous time- and cell-specific knockdown and have
      applied this to reveal temporal profiles of the Ras-MAPK pathway in the control
      of exploratory behavior under poor environmental conditions.

PMID- 25603801
TI  - Culturally tailored diabetes prevention in the workplace: focus group interviews
      with Hispanic employees.
AB  - PURPOSE: The purpose was to conduct focus groups with Hispanic employees to
      obtain input into adaptation of previous DSME interventions for use as a
      workplace diabetes prevention program. METHODS: From a list of interested
      Hispanic employees who attended a local health fair (n = 68), 36 were randomly
      selected to participate in focus groups held during supper mealtime breaks. An
      experienced bilingual moderator directed the sessions, using interview guidelines
      developed by the research team. RESULTS: Participants' ages ranged from 22 to 65
      years (mean = 50.4, n = 36, SD = 10.7), 7 males and 29 females attended, and 53%
      had type 2 diabetes mellitus (T2DM). Employees expressed a keen interest in
      diabetes classes and recommended a focus on preparing healthier Hispanic foods.
      Primary barriers to promoting healthier lifestyles were work schedules; many
      employees worked 2 part-time or full-time jobs. Administrators and direct
      supervisors of the employees were highly supportive of a workplace diabetes
      prevention program. CONCLUSIONS: The consistent message was that a workplace
      program would be the ideal solution for Hispanic employees to learn about
      diabetes and healthy behaviors, given their busy schedules, family
      responsibilities, and limited resources. If found to be effective, such a
      workplace program would be generalizable to other service employees who have
      disproportionate diabetes rates.

PMID- 25603802
TI  - Mesh-covered embolic protection stent implantation in ST-segment-elevation
      myocardial infarction: final 1-year clinical and angiographic results from the
      MGUARD for acute ST elevation reperfusion trial.
AB  - BACKGROUND: The MGuard, a bare metal stent covered with a polymer mesh, was
      designed to reduce distal embolization during percutaneous coronary intervention
      in ST-segment-elevation myocardial infarction. In the MGUARD for Acute ST
      Elevation Reperfusion trial, the primary end point of complete ST-segment
      resolution was significantly improved with the MGuard compared with control. We
      evaluated 1-year clinical and angiographic results. METHODS AND RESULTS: Patients
      with ST-segment-elevation myocardial infarction <=12 hours undergoing primary
      percutaneous coronary intervention of a single de novo native lesion were
      randomized to the MGuard versus any commercially available metallic stent (39.8%
      drug-eluting). Clinical follow-up was performed through 1 year, and angiography
      at 13 months was planned in 50 MGuard patients. There was no difference in major
      adverse cardiac events (1.8% versus 2.3%; P=0.75) at 30 days between the groups.
      Major adverse cardiac events at 1 year were higher with the MGuard, driven by
      greater ischemia-driven target lesion revascularization (8.6% versus 0.9%;
      P=0.0003). Conversely, mortality tended to be lower with the MGuard at 30 days
      (0% versus 1.9%; P=0.04) and at 1 year (1.0% versus 3.3%; P=0.09). Late lumen
      loss at 13 months in the MGuard was 0.99+/-0.80 mm, and binary restenosis was
      31.6%. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction
      undergoing primary percutaneous coronary intervention, a trend toward reduced 1
      year mortality was present in patients treated with the MGuard stent. Target
      lesion revascularization and major adverse cardiac events rates during follow-up
      were higher in the MGuard group than in the control stent group, and angiographic
      late loss of the MGuard was consistent with that expected from bare metal stents.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01368471.

PMID- 25603803
TI  - TGFbeta1a regulates zebrafish posterior lateral line formation via Smad5 mediated
      pathway.
AB  - The zebrafish sensory posterior lateral line (pLL) has become an attractive model
      for studying collective cell migration and cell morphogenesis. Recent studies
      have indicated that chemokine, Wnt/beta-catenin, Fgf, and Delta-Notch signaling
      pathways participate in regulating pLL development. However, it remains unclear
      whether TGFbeta signaling pathway is involved in pLL development. Here we report
      a critical role of TGFbeta1 in regulating morphogenesis of the pLL primordium
      (pLLP). The tgfbeta1a gene is abundantly expressed in the lateral line
      primordium. Knockdown or knockout of tgfbeta1a leads to a reduction of neuromast
      number, an increase of inter-neuromast distance, and a reduced number of hair
      cells. The aberrant morphogenesis in embryos depleted of tgfbeta1a correlates
      with the reduced expression of atoh1a, deltaA, and n-cadherin/cdh2, which are
      known important regulators of the pLLP morphogenesis. Like tgfbeta1a depletion,
      knockdown of smad5 that expresses in the pLLP, affects pLLP development whereas
      overexpression of a constitutive active Smad5 isoform rescues the defects in
      embryos depleted of tgfbeta1a, indicating that Smad5 mediates tgfbeta1a function
      in pLLP development. Therefore, TGFbeta/Smad5 signaling plays an important role
      in the zebrafish lateral line formation. 

PMID- 25603805
TI  - Why there's no point telling me to lose weight.

PMID- 25603804
TI  - Endothelial Cell Inflammation and Antioxidant Capacity are Associated With
      Exercise Performance and Microcirculation in Patients With Symptomatic Peripheral
      Artery Disease.
AB  - We determined whether exercise performance and lower extremity microcirculation
      were associated with endothelial cell inflammation, oxidative stress, and
      apoptosis and with circulating biomarkers of inflammation and antioxidant
      capacity in 160 patients with symptomatic peripheral artery disease (PAD). In a
      multivariate regression model for peak walking time, significant independent
      variables included ankle-brachial index (P < .001), age (P = .017), hydroxyl
      radical antioxidant capacity (P = .008), and endothelial cell nuclear factor K
      light-chain-enhancer of activated B cells (NF-kappaB) activity (P = .015). In
      multivariate analyses for time to minimum exercise calf muscle hemoglobin oxygen
      saturation (StO2), significant independent variables included endothelial cell NF
      kappaB activity (P = .043) and calf muscle StO2 at rest (P = .007). Endothelial
      cell inflammation and circulating biomarkers of inflammation and antioxidant
      capacity were associated with exercise performance and microcirculation of the
      ischemic calf musculature during exercise. The clinical implication is that
      interventions designed to alleviate endothelial cell inflammation and circulating
      inflammatory biomarkers, such as antioxidant therapy, may improve exercise
      performance of symptomatic patients with PAD.

PMID- 25603807
TI  - Computational fluid dynamics with stents: quantitative comparison with particle
      image velocimetry for three commercial off the shelf intracranial stents.
AB  - BACKGROUND AND PURPOSE: Validation of computational fluid dynamics (CFD) in
      stented intracranial aneurysms (IAs) is still lacking, to reliably predict prone
      to occlusion hemodynamics, probing, in particular, velocity reduction, and flow
      pattern changes. This study compares CFD outcome with particle imaging
      velocimetry (PIV) for three commercial off the shelf (COTS) stents of different
      material densities. MATERIAL AND METHODS: The recently developed uniform and high
      precision multi-time lag PIV method was applied to a sidewall aneurysm before and
      after implantation of three COTS stents with high, intermediate, and low material
      densities. The measured laser sheet flow patterns and velocity reductions were
      compared with CFD results and correlated with stent material density. RESULTS:
      Velocity reduction was in good agreement for unstented high and low porosity
      stented IA, while flow pattern change was fully matched for unstented and high
      porosity stented IA. Poor CFD-PIV matching in IA was found for intermediate
      porosity stents. CONCLUSIONS: CFD reproduced fully PIV measurements in unstented
      and high porosity stented IAs. With low porosity stents, CFD reproduced velocity
      reduction and high velocities close to the neck, while a marked mismatch on
      sluggish flow was found at the dome. CFD was unable to match PIV with
      intermediate porosity stents for which hemodynamic transition occurred.

PMID- 25603806
TI  - Computer-supported feedback message tailoring: theory-informed adaptation of
      clinical audit and feedback for learning and behavior change.
AB  - BACKGROUND: Evidence shows that clinical audit and feedback can significantly
      improve compliance with desired practice, but it is unclear when and how it is
      effective. Audit and feedback is likely to be more effective when feedback
      messages can influence barriers to behavior change, but barriers to change differ
      across individual health-care providers, stemming from differences in providers'
      individual characteristics. DISCUSSION: The purpose of this article is to invite
      debate and direct research attention towards a novel audit and feedback component
      that could enable interventions to adapt to barriers to behavior change for
      individual health-care providers: computer-supported tailoring of feedback
      messages. We argue that, by leveraging available clinical data, theory-informed
      knowledge about behavior change, and the knowledge of clinical supervisors or
      peers who deliver feedback messages, a software application that supports
      feedback message tailoring could improve feedback message relevance for barriers
      to behavior change, thereby increasing the effectiveness of audit and feedback
      interventions. We describe a prototype system that supports the provision of
      tailored feedback messages by generating a menu of graphical and textual messages
      with associated descriptions of targeted barriers to behavior change. Supervisors
      could use the menu to select messages based on their awareness of each feedback
      recipient's specific barriers to behavior change. We anticipate that such a
      system, if designed appropriately, could guide supervisors towards giving more
      effective feedback for health-care providers. A foundation of evidence and
      knowledge in related health research domains supports the development of feedback
      message tailoring systems for clinical audit and feedback. Creating and
      evaluating computer-supported feedback tailoring tools is a promising approach to
      improving the effectiveness of clinical audit and feedback.

PMID- 25603808
TI  - Flow diverter device for the treatment of small middle cerebral artery aneurysms.
AB  - PURPOSE: Experience with the endovascular treatment of middle cerebral artery
      (MCA) aneurysms by flow diverter devices (FDD) is still limited. This study
      examines the results and complications of FDD for small aneurysms at this
      location. METHODS: From February 2010 to December 2013, 14 patients (10 women;
      mean age 59 years) with 15 small MCA aneurysms were treated with FDD. All
      procedures were performed with the Pipeline embolization device (PED). RESULTS:
      Complete occlusion was obtained in 12/15 aneurysms (80%) and partial occlusion in
      3 (20%). Among 13 aneurysms with a side branch, this was patent at the
      angiographic control in 4 cases, showed decreased filling in 6, and was occluded
      in 3 (with neurological deficits in 2). All PEDs were patent at follow-up. Post
      procedural ischemic complications occurred in 4 (27%) procedures with permanent
      neurological deficit (modified Rankin score 2) in 3 (21%). No early or delayed
      aneurysm rupture, no subarachnoid or intraparenchymal hemorrhage and no deaths
      occurred. CONCLUSIONS: Endovascular treatment with FDD is a relatively safe
      treatment for small MCA aneurysms resulting in a high occlusion rate. The
      findings of this study suggest that complete occlusion after endovascular
      treatment with FDD can be delayed (>6 months). Ischemic complications may occur
      as early or delayed, particularly at clopidogrel interruption.

PMID- 25603810
TI  - Robustness analysis on interspecies interaction network for iron and glucose
      competition between Candida albicans and zebrafish during infection.
AB  - Candida albicans has emerged as an important model organism for the study of
      infectious disease. Using high-throughput simultaneously quantified time-course
      transcriptomics, this study constructed host-pathogen interspecies interaction
      networks between C. albicans and zebrafish during the adhesion, invasion, and
      damage stages. Given that iron and glucose have been identified as crucial
      resources required during the infection process between C. albicans and
      zebrafish, we focused on the construction of the interspecies networks associated
      with them. Furthermore, a randomization technique was proposed to identify
      differentially regulated proteins that are statistically eminent for the three
      infection stages. The behaviors of the highly connected or differentially
      regulated proteins identified from the resulting networks were further
      investigated. "Robustness" is an important system property that measures the
      ability of the system tolerating the intrinsic perturbations in a dynamic
      network. This characteristic provides a systematic and quantitative view to
      elucidate the dynamics of iron and glucose competition in terms of the
      interspecies interaction networks. Here, we further estimated the robustness of
      our constructed interspecies interaction networks for the three infection stages.
      The constructed networks and robustness analysis provided significant insight
      into dynamic interactions related to iron and glucose competition during
      infection and enabled us to quantify the system's intrinsic perturbation
      tolerance ability during iron and glucose competition throughout the three
      infection stages. Moreover, the networks also assist in elucidating the offensive
      and defensive mechanisms of C. albicans and zebrafish during their competition
      for iron and glucose. Our proposed method can be easily extended to identify
      other such networks involved in the competition for essential resources during
      infection.

PMID- 25603811
TI  - Development and validation of a symptom-based severity score for haemorrhoidal
      disease: the Sodergren score.
AB  - AIM: One major obstacle in assessing the efficacy of treatment of haemorrhoids
      and the comparison of trials has been the lack of a standardized, validated
      symptom severity score. This study aimed to develop an objective, validated
      symptom-based score of severity for haemorrhoids that can be used to compare
      treatments, monitor disease and assist in surgical decisions. METHOD: A symptom
      and quality-of-life questionnaire was developed from the literature in
      conjunction with expert surgical opinion. The questionnaire was circulated to
      patients with confirmed haemorrhoids. A statistical model was used to derive a
      weighted score of symptoms most affecting patients' quality of life. Patients who
      were offered operative treatment were independently judged by specialists to have
      more severe symptoms, with further validation of the scoring system against
      treatment. RESULTS: Forty-five patients were included in final validation
      analysis, of whom 44 (98%) reported multiple symptoms, the most common being
      rectal bleeding. Patient-reported effects on quality of life were 47.5 +/- 36.3
      (1-100 visual analogue scale). Calculated symptom severity scores were used to
      compare patients receiving operative or ambulatory care, with significant
      difference in the scores (7.7 +/- 3.9 vs 2.8 +/- 3.5, P = 0.002) and a receiver
      operating characteristic area under the curve of 0.842. CONCLUSION: A novel
      validated score for the assessment of haemorrhoidal disease adopting a
      standardized global score for symptom severity may have important implications in
      future for research, assessment and the management of this common pathology.

PMID- 25603809
TI  - Histopathological features predict metastatic potential in locally advanced colon
      carcinomas.
AB  - BACKGROUND: Metastatic dissemination can exist before a pathologically and
      clinically detectable manifestation. The structural heterogeneity of colon cancer
      (CC) in histological sections with respect to the morphology of tumor
      aggressiveness and composition of the tumor microenvironment raises the question
      of whether the microscopical tumor architecture enables a discrimination of
      groups with different metastatic potential. This would result in an assessment of
      the prognosis and provision of an ancillary tool for the therapeutic management
      after surgery, beside the estimation of the local tumor extent. METHODS: In order
      to identify predictive biomarkers for metastasis of locally advanced CC, which
      can easily be integrated into the pathologist's daily routine diagnostic
      activity, we determined tumor budding, peritumoral inflammation, extent of
      desmoplasia and necrosis, density of macro- and microvascular blood vessels and
      functional state of lymphatics in the tumor center, invasive margin and tumor
      free surrounding tissue in 86 non-metastatic, lymphogenous-metastatic and
      haematogenous-metastatic, subserosa-invasive CC. RESULTS: Features influencing
      nodal metastasis in the univariate analysis included high tumor budding (p =
      0.004), high large vessel density in the subserosa (p = 0.043), abundant
      desmoplasia (p = 0.049), non-finger-like desmoplastic pattern (p = 0.051) and
      absent lymphocellular intratumoral inflammation (p = 0.084). In the multivariate
      analysis, with the exception of large vessel density, these pathomorphological
      features were independent risk factors for lymphogenous metastasis (p = 0.023, p
      = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability
      (AUC of 0.853). Features associated with distant metastasis in the univariate
      analysis included high tumor budding (p = 0.002), low intratumoral small vessel
      density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048)
      and abundant necrosis (p = 0.073). In the multivariate analysis only tumor
      budding was an independent predictor for haematogenous metastasis (p = 0.007)
      with a good discrimination ability (AUC of 0.829). CONCLUSIONS: Thus, mainly
      tumor budding but also the described structural characteristics of the
      peritumoral tissue appears to reflect the metastatic potential of locally
      advanced CC and therefore should be stated in pathological reports.

PMID- 25603812
TI  - High-throughput plasmid construction using homologous recombination in yeast: its
      mechanisms and application to protein production for X-ray crystallography.
AB  - Homologous recombination is a system for repairing the broken genomes of living
      organisms by connecting two DNA strands at their homologous sequences. Today,
      homologous recombination in yeast is used for plasmid construction as a
      substitute for traditional methods using restriction enzymes and ligases. This
      method has various advantages over the traditional method, including flexibility
      in the position of DNA insertion and ease of manipulation. Recently, the author
      of this review reported the construction of plasmids by homologous recombination
      in the methanol-utilizing yeast Pichia pastoris, which is known to be an
      excellent expression host for secretory proteins and membrane proteins. The
      method enabled high-throughput construction of expression systems of proteins
      using P. pastoris; the constructed expression systems were used to investigate
      the expression conditions of membrane proteins and to perform X-ray
      crystallography of secretory proteins. This review discusses the mechanisms and
      applications of homologous recombination, including the production of proteins
      for X-ray crystallography. 

PMID- 25603814
TI  - Growth suppression and cell death by pyridoxal is dependent on p53 in the human
      breast cancer cell line MCF-7.
AB  - Vitamin B6 compound, pyridoxine (PN), has shown antitumor action. Our previous
      experiments showed that PN induces expression of insulin-like growth factor
      binding protein-3 to arrest proliferation and induce cell death. This induction
      is inhibited by the p53-specific inhibitor pifithrin-alpha. Here, we report that
      another B6 compound, pyridoxal (PL), strongly inhibited MCF-7 cell growth
      compared to PN. PL induced the G0/G1 arrest and the accumulation of subG1
      population. Although p53 mRNA was not changed by PL, 0.5 mM PL increased the
      protein level in MCF-7 cells. The cell growth suppression by 0.5 mM PL did not
      occur when p53 expression was knocked down using siRNA. Together, these data
      suggest that PL accumulate p53 and PL-induced cell growth suppression is
      dependent on p53 in MCF-7 breast cancer cells. 

PMID- 25603813
TI  - Tomato extract suppresses the production of proinflammatory mediators induced by
      interaction between adipocytes and macrophages.
AB  - Obese adipose tissue is characterized by enhanced macrophage infiltration. A loop
      involving monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor
      alpha (TNFalpha) between adipocytes and macrophages establishes a vicious cycle
      that augments inflammatory changes and insulin resistance in obese adipose
      tissue. Tomatoes, one of the most popular crops worldwide, contain many
      beneficial phytochemicals that improve obesity-related diseases such as diabetes.
      Some of them have also been reported to have anti-inflammatory properties. In
      this study, we focused on the potential protective effects of phytochemicals in
      tomatoes on inflammation. We screened fractions of tomato extract using nitric
      oxide (NO) assay in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. One
      fraction, RF52, significantly inhibited NO production in LPS-stimulated RAW264
      macrophages. Furthermore, RF52 significantly decreased MCP-1 and TNFalpha
      productions. The coculture of 3T3-L1 adipocytes and RAW264 macrophages markedly
      enhanced MCP-1, TNFalpha, and NO productions compared with the control cultures;
      however, the treatment with RF52 inhibited the production of these
      proinflammatory mediators. These results suggest that RF52 from tomatoes may have
      the potential to suppress inflammation by inhibiting the production of NO or
      proinflammatory cytokines during the interaction between adipocytes and
      macrophages. 

PMID- 25603815
TI  - Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion
      injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation.
AB  - Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing
      factor/visfatin (Nampt/PBEF/visfatin) is an adipocytokine. By synthesizing
      nicotinamide adenine dinucleotide (NAD(+)), Nampt/PBEF/visfatin functions to
      maintain an energy supply that has critical roles in cell survival. Cerebral
      ischemia leads to energy depletion and eventually neuronal death by apoptosis in
      specific brain regions specially the hippocampus. However, the role of
      Nampt/PBEF/visfatin in brain and cerebral ischemia remains to be investigated.
      This study investigated the role of administration Nampt/PBEF/visfatin in
      hippocampal CA3 area using a transient global cerebral ischemia model. Both
      common carotid arteries were occluded for 20 min followed by reperfusion. Saline
      as a vehicle and Nampt/PBEF/visfatin at a dose of 100 ng were injected
      intracerebroventricularly (ICV) at the time of cerebral reperfusion. To
      investigate the underlying mechanisms of Nampt/PBEF/visfatin neuroprotection,
      levels of expression of apoptosis-related proteins (caspase-3 activation, Bax
      protein levels, and Bcl-2 protein levels) 96 h after ischemia were determined by
      immunohistochemical staining. The number of active caspase-3-positive neurons in
      CA3 was significantly increased in the ischemia group, compared with the sham
      group (P < 0.001), and treatment with Nampt/PBEF/visfatin significantly reduced
      the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia
      group (P < 0.05). Also, results indicated a significant increase in Bax/Bcl-2
      ratio in the ischemia group, compared with the sham group (P < 0.01). However,
      treatment with Nampt/PBEF/visfatin significantly attenuated the
      ischemia/reperfusion-induced increase in Bax/Bcl-2 ratio, compared with the
      ischemia group (P < 0.05). This study has indicated that Nampt/PBEF/visfatin
      entails neuroprotective effects against ischemia injury when used at the time of
      cerebral reperfusion. These neuroprotective mechanisms of Nampt/PBEF/visfatin
      occur through decrease the expression ofproapoptotic proteins (cleaved caspase-3
      and Bax) and, on the other hand, increase the expression ofantiapoptotic proteins
      (Bcl-2). Thus, our findings indicate that Nampt/PBEF/visfatin is a new
      therapeutic target for cerebral ischemia.

PMID- 25603816
TI  - The Expression and Significance of the Plasma Let-7 Family in Anti-N-methyl-D
      aspartate Receptor Encephalitis.
AB  - The study aimed to investigate the expression and significance of the plasma let
      7 family in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Blood
      samples from 5 anti-NMDAR encephalitis patients and 5 negative controls were
      collected for microarray analysis. Blood samples from10 anti-NMDAR encephalitis
      patients, 10 anti-NMDAR encephalitis patients whose physical conditions have
      improved after 3 months of immunotherapy, 20 virus (meningitis) encephalitis
      patients, 20 tuberculosis (meningitis) encephalitis patients, 10 purulent
      (meningitis) encephalitis patients, 20 cerebral cysticercosis patients, 20
      ischemic stroke patients, 20 intracerebral hemorrhage patients, 15 neuromyelitis
      optica patients, 15 multiple sclerosis patients, 15 moyamoya disease patients,
      and 20 negative controls were collected for real-time quantitative PCR (qRT-PCR)
      analysis. The expression levels of let-7a, let-7b, let-7d, and let-7f were
      significantly down-regulated in anti-NMDAR encephalitis compared with the
      negative controls (NC). The expression levels of let-7a, let-7d, and let-7f were
      significantly down-regulated in other nervous system diseases compared with the
      NC group while the expression level of let-7b was statistically insignificant in
      other nervous system diseases compared with the NC group. In addition, there was
      no significant dysregulation of let-7b in the anti-NMDAR encephalitis treatment
      group compared with the NC. Let-7b may be a potential diagnostic marker and an
      indicator that reflected the molecular mechanism of anti-NMDAR encephalitis.

PMID- 25603817
TI  - Present status of the experimental aspect of RFe2O4 study.
AB  - We give a brief review of the experimental research on a triangular mixed valence
      iron oxide RFe2O4 (R = Y, Dy, Ho, Er, Tm, Yb, Lu, Sc or In). Interest in this
      material has been increasing every year because of the fascinating but
      complicated interaction between spin, charge and the orbital state of iron ions
      in frustrated geometry. Reports collected in this review cover experimental
      research on crystallography, chemical analysis, bulk and thin film preparation,
      magnetic, dielectric, diffraction with neutrons, x-ray and electron, optical and
      x-ray absorption, Mossbauer spectroscopy and other methods that incorporate the
      use of modern scientific technology and knowledge. The report mainly focuses on
      experimental facts since 1990 on which an early review by Siratori has been
      published (Kimizuka et al 1990 Handbook on the Physics and Chemistry of Rare
      Earths vol 13, ed K A Gschneidner Jr and L Eyring (Amsterdam: North
      Holland/Elsevier) pp 283-384). 

PMID- 25603818
TI  - Determinants of low socio-economic status and risk of Plasmodium vivax malaria
      infection in Panama (2009-2012): a case-control study.
AB  - BACKGROUND: Identification of risk factors is important for the establishment of
      malaria elimination programmes tailored to specific regions. Type of house
      construction had been associated with increasing risk of acquiring malaria. This
      study aimed at establishing the association between determinants of low socio
      economic status (SES) and type of house construction with the likelihood of
      living in a Plasmodium vivax malarious corregimiento (smallest political
      division) in Panama during 2009-2012. METHODS: To determine the association
      between type-2 houses (build with deciduous materials) and other determinants of
      low SES, with living in a malarious corregimiento, this study analyzed
      demographic and housing census data (2010), and malaria incidence aggregated at
      the corregimiento level (2009-2012), using a Spearman's non-parametric
      correlation test to explore for associations, followed by a case-control study
      and a reduced multivariate logistic regression approach for confirmation.
      RESULTS: A descriptive temporal and spatial analysis indicated that P. vivax in
      Panama was associated with Amerindian reservations. Moreover, this study
      demonstrated that a strong correlation (deleterious effect) existed between
      living in a malarious corregimiento and being exposed to a type-2 house (OR = >
      1.0) (p < 0.001), while, it showed an inverse correlation for exposure to type-1
      houses (protective effect) (build with permanent materials) (OR = < 1.0) (p <
      0.001). In the same way, a significant association between exposure to type-2
      houses and the outcome of living in a malarious corregimiento was found using a
      case-control study approach (Chi(2) test = p < 0.001), that was confirmed
      applying a reduced multivariate logistic regression fitted model. CONCLUSIONS:
      This study demonstrated that living in a P. vivax malarious corregimiento in
      Panama during 2009-2012 was strongly correlated with those corregimientos having
      a high proportion of type-2 houses. A multivariate logistic regression approach
      at the house and corregimiento level indicated a strong association of type-2
      houses, dirt floors and illiteracy with the likelihood of living in a malarious
      corregimiento. It is expected that these findings will help implement a multi
      sectorial approach for the elimination of malaria in poor areas of Panama where
      malaria is endemic, which emphasizes house improvements such as mosquito-proofing
      and socio-economic development.

PMID- 25603819
TI  - Comparable liraglutide pharmacokinetics in pediatric and adult populations with
      type 2 diabetes: a population pharmacokinetic analysis.
AB  - BACKGROUND AND OBJECTIVE: The safety, tolerability, and pharmacokinetics of the
      once-daily human glucagon-like peptide-1 (GLP-1) analog liraglutide have been
      evaluated in pediatric patients aged greater than 10 years with type 2 diabetes
      (T2D). In this study, a population pharmacokinetic analysis was compared to the
      pediatric pharmacokinetic data with those from two clinical pharmacology trials
      in adults with T2D. METHODS: A one-compartment pharmacokinetic model previously
      found to adequately describe the pharmacokinetics of liraglutide in adults with
      T2D was applied to the evaluation of 13 pediatric subjects (10-17 years of age)
      with T2D. Steady-state estimates for apparent clearance (CL/F) for individual
      subjects and corresponding dose were used to derive the area under the plasma
      concentration time curve from 0-24 h (AUC24) and investigate dose proportionality
      in the pediatric trial. A covariate analysis evaluated the effects of body
      weight, gender, and age category (pediatric/adult) on liraglutide exposure.
      RESULTS: Dose proportionality in the dose range of 0.3-1.8 mg was indicated by
      the model-derived AUC24 slope: 1.05 (95% CI 0.96-1.15). Consistent with findings
      from adult trials, body weight and gender were relevant covariates for
      liraglutide exposure in the pediatric population. The CL/F estimates, and thus
      exposure, for the pediatric subjects with T2D were similar to those in the adult
      trials. CONCLUSION: Based on this population pharmacokinetic analysis, the
      liraglutide dose regimen that was found to be clinically effective in adults is
      predicted to achieve the same range of exposure in the pediatric population (10
      17 years of age) with a pre-trial body weight range of 57-214 kg.

PMID- 25603820
TI  - Nitrite: on the journey from toxin to therapy.

PMID- 25603821
TI  - Paraxanthine/Caffeine Concentration Ratios in Hair: An Alternative for Plasma
      Based Phenotyping of Cytochrome P450 1A2?
AB  - BACKGROUND AND OBJECTIVE: Although metabolite-to-parent drug concentration ratios
      in hair have been suggested as a possible tool to study the metabolism of drugs
      in a non-invasive way, no studies are available that evaluated this in a
      systematic way. Cytochrome P450 (CYP) 1A2 is a drug-metabolizing enzyme
      characterized by large inter-individual differences in its activity. The standard
      approach for CYP1A2 phenotyping is to determine the paraxanthine/caffeine ratio
      in plasma at a fixed timepoint after intake of a dose of the CYP1A2 substrate
      caffeine. The aim of this study was to evaluate whether paraxanthine/caffeine
      ratios measured in hair samples reflect the plasma-based CYP1A2 phenotype.
      METHODS: Caffeine and paraxanthine concentrations were measured in proximal 3 cm
      segments of hair samples from 60 healthy volunteers and resulting
      paraxanthine/caffeine ratios were correlated with CYP1A2 phenotyping indices in
      plasma. RESULTS: Paraxanthine/caffeine ratios in hair ranged from 0.12 to 0.93
      (median 0.41); corresponding ratios in plasma ranged from 0.09 to 0.95 (median
      0.40). A statistically significant correlation was found between ratios in hair
      and plasma (r = 0.41, p = 0.0011). However, large deviations between ratios in
      both matrices were found in individual cases. Although the influence of several
      factors on paraxanthine/caffeine ratios and hair-plasma deviations was
      investigated, no evident factors explaining the observed variability could be
      identified. CONCLUSION: The variability between hair and plasma ratios
      complicates the interpretation of hair paraxanthine/caffeine ratios on an
      individual basis and, therefore, compromises their practical usefulness as
      alternative CYP1A2 phenotyping matrix.

PMID- 25603822
TI  - Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild
      to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C
      Virus-Seropositive Subjects, and in Healthy Volunteers.
AB  - BACKGROUND AND OBJECTIVES: Suboxone((r)) is a sublingual tablet of
      buprenorphine/naloxone, approved for the treatment of opioid dependence. The
      objective of this study was to quantify the impact of hepatic impairment or
      hepatitis C virus infection on the pharmacokinetics of buprenorphine or naloxone
      and their major metabolites. METHODS: Forty-three subjects received a single dose
      of a Suboxone 2.0/0.5-mg tablet. Blood samples were collected up to 168 h and
      pharmacokinetic parameters were calculated using non-compartmental analysis.
      Statistical analysis was performed using analysis of covariance. RESULTS:
      Pharmacokinetic parameters were derived from 33 subjects. Compared with healthy
      subjects, for patients with severe hepatic impairment, total and peak exposures
      increased to 281.4 % [90 % confidence interval 187.1-423.3] and 171.8 % [117.9
      250.2] for buprenorphine, 1401.9 % [707.6-2777.5] and 1129.8 % [577.2-2211.4] for
      naloxone. For moderate hepatic impaired subjects, naloxone total and peak
      exposure increased to 317.6 % [164.9-611.5] and 270.0  % [141.9-513.9]. For
      buprenorphine, only total exposure increased to 163.9 % [110.8-242.3]. Changes in
      maximum observed plasma concentration, area under the plasma concentration-time
      curve from time zero to time of the last quantifiable concentration, and area
      under the plasma concentration-time curve from time zero to infinity of
      buprenorphine or naloxone in subjects with mild hepatic impairment or with
      hepatitis C virus infection were within twofold of those of healthy subjects.
      Serious adverse events were not observed. CONCLUSIONS: Severe and moderate
      hepatic impairment significantly increased exposure of naloxone and to a lesser
      extent of buprenorphine. Therefore, buprenorphine/naloxone combination products
      should generally be avoided in patients with severe hepatic impairment and may
      not be appropriate for patients with moderate hepatic impairment. However,
      buprenorphine/naloxone products may be used with caution for maintenance
      treatment in patients with moderate hepatic impairment who have initiated
      treatment on a buprenorphine product without naloxone [Registered at
      ClinicalTrials.gov as NCT01846455].

PMID- 25603824
TI  - Removal of migrated dental implants from maxillary sinus 4 years 10 months after
      implant placement.
AB  - INTRODUCTION: Dental implant treatment has been applied widely in recent years.
      However, several complications sometimes have been reported. Although
      displacement of dental implants into the maxillary sinus commonly occurs during
      surgery, the migration of dental implants after a period of function, especially
      several years after dental implant placement, is very rare. CASE REPORT: We
      report here removal of migrated dental implants from the maxillary sinus 4 years
      and 10 months after dental implant placement.

PMID- 25603823
TI  - Interferon-alpha and angiogenic dysregulation in pregnant lupus patients who
      develop preeclampsia.
AB  - OBJECTIVE: To investigate whether an elevated interferon-alpha (IFNalpha) level
      early in pregnancy is associated with poor pregnancy outcomes and to examine the
      relationship of an elevated IFNalpha level to angiogenic imbalance. METHODS:
      Women were enrolled in a longitudinal case-control study of pregnant patients
      with lupus. Serum samples obtained monthly throughout pregnancy were assayed for
      IFNalpha and for the antiangiogenic factor soluble Flt-1 and the proangiogenic
      factor placenta growth factor (PlGF). Each of 28 patients with systemic lupus
      erythematosus (SLE) with a poor pregnancy outcome was matched to an SLE patient
      with an uncomplicated pregnancy and to a pregnant healthy control. The effects of
      IFNalpha and/or soluble Flt-1 on human endothelial cells and endothelial cell
      trophoblast interactions were assessed. RESULTS: Compared to SLE patients with
      uncomplicated pregnancies, patients with preeclampsia had increased IFNalpha
      levels before clinical symptoms. Patients without autoimmune disease who
      developed preeclampsia did not have increased IFNalpha levels. In SLE patients
      with low IFNalpha levels, marked angiogenic imbalance (higher soluble Flt-1,
      lower PlGF, and higher soluble Flt-1:PlGF ratios) preceded maternal
      manifestations of preeclampsia, whereas in SLE patients with high IFNalpha
      levels, preeclampsia occurred without evidence of systemic angiogenic imbalance.
      Treatment of human endothelial cells with soluble Flt-1 induced expression of
      sFLT1 messenger RNA, and IFNalpha dramatically amplified responses to soluble Flt
      1. In a model of spiral artery transformation, only the combination of IFNalpha
      and soluble Flt-1 disrupted the ability of trophoblast cells to remodel
      endothelial tube structures. CONCLUSION: Our findings identify a new mechanism by
      which IFNalpha induces an antiangiogenic milieu and increases the sensitivity of
      endothelial cells to soluble Flt-1, and suggest that elevated IFNalpha levels may
      contribute to the pathogenesis of preeclampsia in some pregnant patients with
      SLE.

PMID- 25603825
TI  - Sialylation of Helicobacter bizzozeronii lipopolysaccharides modulates Toll-like
      receptor (TLR) 2 mediated response.
AB  - Sialic acid in lipopolysaccharides (LPS) of mucosal pathogens is known to be an
      important virulence factor. Few strains of Helicobacter pylori express sialyl
      Lewis-X and we have reported that human and canine Helicobacter bizzozeronii
      strains express sialyl-lactoseamine in their LPS. However, the role of sialyation
      of Helicobacter LPS in the interaction with the host cells is still unknown. In
      this study H. bizzozeronii LPS is shown to activate the TLR2 in a dose and strain
      dependent manner in the in vitro HEK-293 cells model expressing TLR2, but not the
      cells expressing TLR4. These results indicate that TLR2 is the specific receptor
      for H. bizzozzeronii LPS, as previously described for H. pylori. To further
      explore the role of sialylation of H. bizzozeronii LPS on TLR2 response, H.
      bizzozeronii Deltahbs2 mutant strains deficient in sialyltransferase activity
      were constructed by homologous recombination. LPS from H. bizzozeronii Deltahbs2
      strains enhanced the NF-KB induction via TLR2 compared to the respective wild
      types, leading to the conclusion that the sialylation of H. bizzozeronii LPS in
      wild-type strains may modulate host immune response. 

PMID- 25603826
TI  - The Axl receptor tyrosine kinase is a discriminator of macrophage function in the
      inflamed lung.
AB  - Much of the biology surrounding macrophage functional specificity has arisen
      through examining inflammation-induced polarizing signals, but this also occurs
      in homeostasis, requiring tissue-specific environmental triggers that influence
      macrophage phenotype and function. The TAM receptor family of receptor tyrosine
      kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic
      cells by phagocytes through the bridging phosphatidylserine-binding molecules
      growth arrest-specific 6 (Gas6) or Protein S. We show that one such TAM receptor
      (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial
      macrophages and other lung leukocytes, under homeostatic conditions and is
      constitutively ligated to Gas6. Axl expression is potently induced by granulocyte
      macrophage colony-stimulating factor expressed in the healthy and inflamed
      airway, and by type I interferon or Toll-like receptor-3 stimulation on human and
      mouse macrophages, indicating potential involvement of Axl in apoptotic cell
      removal under inflammatory conditions. Indeed, an absence of Axl does not cause
      sterile inflammation in health, but leads to exaggerated lung inflammatory
      disease upon influenza infection. These data imply that Axl allows specific
      identification of airway macrophages, and that its expression is critical for
      macrophage functional compartmentalization in the airspaces or lung interstitium.
      We propose that this may be a critical feature to prevent excessive inflammation
      because of secondary necrosis of apoptotic cells that have not been cleared by
      efferocytosis. 

PMID- 25603828
TI  - Persistent expression of CXCR5 on plasmablasts in IgG4-related disease.

PMID- 25603827
TI  - Gastric LTi cells promote lymphoid follicle formation but are limited by IRAK-M
      and do not alter microbial growth.
AB  - Lymphoid tissue inducer (LTi) cells are activated by accessory cell IL-23, and
      promote lymphoid tissue genesis and antibacterial peptide production by the
      mucosal epithelium. We investigated the role of LTi cells in the gastric mucosa
      in the context of microbial infection. Mice deficient in IRAK-M, a negative
      regulator of TLR signaling, were investigated for increased LTi cell activity,
      and antibody mediated LTi cell depletion was used to analyze LTi cell dependent
      antimicrobial activity. H. pylori infected IRAK-M deficient mice developed
      increased gastric IL-17 and lymphoid follicles compared to wild type mice. LTi
      cells were present in naive and infected mice, with increased numbers in IRAK-M
      deficient mice by two weeks. Helicobacter and Candida infection of LTi cell
      depleted rag1(-/-) mice demonstrated LTi-dependent increases in calprotectin but
      not RegIII proteins. However, pathogen and commensal microbiota populations
      remained unchanged in the presence or absence of LTi cell function. These data
      demonstrate LTi cells are present in the stomach and promote lymphoid follicle
      formation in response to infection, but are limited by IRAK-M expression.
      Additionally, LTi cell mediated antimicrobial peptide production at the gastric
      epithelium is less efficacious at protecting against microbial pathogens than has
      been reported for other tissues. 

PMID- 25603830
TI  - When gout goes to the heart: does gout equal a cardiovascular disease risk
      factor?

PMID- 25603829
TI  - Tribbles homologue 3 stimulates canonical TGF-beta signalling to regulate
      fibroblast activation and tissue fibrosis.
AB  - OBJECTIVES: Tribbles homologue 3 (TRB3) is a pseudokinase that modifies the
      activation of various intracellular signalling pathways to control fundamental
      processes extending from mitosis and cell activation to apoptosis and modulation
      of gene expression. Here, we aimed to analyse the role of TRB3 in fibroblast
      activation in systemic sclerosis (SSc). METHODS: The expression of TRB3 was
      quantified by quantitative PCR, western blot and immunohistochemistry. The role
      of TRB3 was analysed in cultured fibroblasts and in experimental fibrosis using
      small interfering RNA (siRNA)-mediated knockdown and overexpression of TRB3.
      RESULTS: TRB3 expression was increased in fibroblasts of patients with SSc and in
      murine models of SSc in a transforming growth factor-beta (TGF-beta)/Smad
      dependent manner. Overexpression of TRB3 stimulated canonical TGF-beta signalling
      and induced an activated phenotype in resting fibroblasts. In contrast, knockdown
      of TRB3 reduced the profibrotic effects of TGF-beta and decreased the collagen
      synthesis. Moreover, siRNA-mediated knockdown of TRB3 exerted potent antifibrotic
      effects and ameliorated bleomycin as well as constitutively active TGF-beta
      receptor I-induced fibrosis with reduced dermal thickening, decreased
      hydroxyproline content and impaired myofibroblast differentiation. CONCLUSIONS:
      The present study characterises TRB3 as a novel profibrotic mediator in SSc. TGF
      beta induces TRB3, which in turn activates canonical TGF-beta/Smad signalling and
      stimulates the release of collagen, thereby inducing a positive feedback loop
      that may contribute to aberrant TGF-beta signalling in SSc.

PMID- 25603831
TI  - Evaluation of reproductive barriers contributes to the development of novel
      interspecific hybrids in the Kalanchoe genus.
AB  - BACKGROUND: Interspecific hybridization is a useful tool in ornamental breeding
      to increase genetic variability and introduce new valuable traits into existing
      cultivars. The successful formation of interspecific hybrids is frequently
      limited by the presence of pre- and post-fertilization barriers. In the present
      study, we investigated the nature of hybridization barriers occurring in crosses
      between Kalanchoe species and evaluated possibilities of obtaining interspecific
      hybrids. RESULTS: The qualitative and quantitative analyses of pollen tube growth
      in situ were performed following intra- and interspecific pollinations. They
      revealed occurrence of pre-fertilization barriers associated with inhibition of
      pollen germination on the stigma and abnormal growth of pollen tubes. Unilateral
      incongruity related to differences in pistil length was also observed. The pollen
      quality was identified as a strong factor influencing the number of pollen tubes
      germinating in the stigma. In relation to post-fertilization barriers, endosperm
      degeneration was a probable barrier hampering production of interspecific
      hybrids. Moreover, our results demonstrate the relation of genetic distance
      estimated by AFLP marker analysis of hybridization partners with cross
      compatibility of Kalanchoe species. At the same time, differences in ploidy did
      not influence the success of interspecific crosses. CONCLUSIONS: Our study
      presents the first comprehensive analysis of hybridization barriers occurring
      within Kalanchoe genus. Reproductive barriers were detected on both, pre- and
      post-fertilization levels. This new knowledge will contribute to further
      understanding of reproductive isolation of Kalanchoe species and facilitate
      breeding of new cultivars. For the first time, interspecific hybrids between K.
      nyikae as maternal plant and K. blossfeldiana as well as K. blossfeldiana and K.
      marnieriana were generated.

PMID- 25603833
TI  - Ovarian preservation in young women with endometrial cancer of endometrioid
      histology.
AB  - OBJECTIVE: To clarify the frequency and risk factors of ovarian metastasis in
      women with endometrial cancer of endometrioid histology. DESIGN: Retrospective
      observational study. SETTING: University of the Ryukyus Japan 1990-2011.
      POPULATION: Eighty-eight women <= 45 years of age with endometrial cancer of only
      endometrioid histology. METHODS: Clinicopathological factors from the medical
      records were used. Fisher's exact test and logistic regression analysis were used
      to analyze predictive factors for ovarian metastasis. MAIN OUTCOME MEASURES: Risk
      factors of ovarian malignancy. RESULTS: All women underwent total abdominal
      hysterectomy, bilateral salpingo-oophorectomy and lymph node dissection. The
      median age was 39 years, and FIGO stage distributions were: stage I, 63 (71.6%)
      women; stage II, 14 (15.9%) women; and stage III, 11 (12.5%) women.
      Pathologically, ovarian metastasis was observed in four (4.5%) women. Only lymph
      node metastasis was a significant predictive factor for ovarian metastasis (p =
      0.0038), and deep myometrial invasion was the only significant factor (p =
      0.0085) for the prediction of lymph node metastasis. No ovarian malignancy was
      found in 72 women with invasion <= 50% myometrial depth and no enlargement of the
      ovaries. We observed ovarian metastasis in two (14.3%) of 14 women with deep
      myometrial invasion without ovarian tumor. CONCLUSION: Ovarian preservation
      surgery might be considered in endometrial cancer of endometrioid histology with
      <= 50% myometrial depth invasion with no ovarian mass after taking into account
      family history.

PMID- 25603832
TI  - Chronic exposure to nanoparticulate TiO2 causes renal fibrosis involving
      activation of the Wnt pathway in mouse kidney.
AB  - Chronic exposure to nano-TiO2 may induce renal fibrosis, and the mechanism of
      this process is not well understood. Therefore, in this study, mice were
      administered nano-TiO2 by intragastric feeding for 9 months, and the urinary
      levels of nephrotoxicity biomarkers, activation of the Wnt pathway, and markers
      of the epithelial-to-mesenchymal transition (EMT) in the kidneys were
      investigated. The findings suggested that exposure to nano-TiO2 increased the
      level of renal titanium accumulation, urinary levels of kidney injury molecule-1
      (1.18 +/- 0.13- to 3.60 +/- 0.41-fold), clusterin (1.40 +/- 0.16- to 5.14 +/-
      0.58-fold), and osteopontin (0.71 +/- 0.08- to 2.41 +/- 0.29-fold), and increased
      levels of renal inflammation and fibrosis. Furthermore, nano-TiO2 increased the
      level of expression of Wnt ligands (Wnt1, Wnt2, Wnt3, Wnt4, Wnt5a, Wnt6, Wnt7a,
      Wnt9a, Wnt10a, and Wnt11, 0.09 +/- 0.02- to 4.84 +/- 0.52-fold), Wnt receptors
      Frizzled (Fz1, Fz5, and Fz7, 0.37 +/- 0.04- to 8.57 +/- 0.91-fold), and
      coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (0.73 +/-
      0.09- to 5.27 +/- 0.56-fold) in the kidney. Wnt signaling components induced by
      nano-TiO2 were corroborated by decreased levels of expression of Wnt antagonist
      related markers (Dkk1, Dkk2, Dkk3, Dkk4, and sFRP/FrzB, -0.06 +/- 0.01- to -0.87
      +/- 0.09-fold) and increased levels of expression of Wnt target genes (Abcb1b,
      cyclin D1, and Myc, 0.03 +/- 0.01- to 2.73 +/- 0.28-fold) and EMT markers Colla1,
      Fn, Twist, and alpha-SMA (0.06 +/- 0.02- to 5.80 +/- 0.61-fold). These findings
      indicate that nano-TiO2 induced renal fibrosis that may be mediated via Wnt
      signaling.

PMID- 25603834
TI  - No association between allergy and current 25-hydroxy vitamin D in serum or
      vitamin D intake.
AB  - AIM: Vitamin D may be involved in allergy development, but there is conflicting
      evidence. We investigated if dietary intake of vitamin D and levels of 25OHD in
      serum differed between allergic and nonallergic adolescents and if serum 25OHD
      correlated with dietary intake of vitamin D or season of blood sampling. METHODS:
      Serum 25-hydroxy vitamin D (25OHD) levels were analysed in 13-year-old subjects
      with atopic eczema (n = 55), respiratory allergy (n = 55) or no allergy (n = 55).
      Intake of fat-containing foods was assessed by food-frequency questionnaires, and
      total daily vitamin D intake was calculated. Logistic regression was used to
      adjust for gender, parental allergy and time of blood sampling. RESULTS: Subjects
      with atopic eczema or respiratory allergy did not differ from nonallergic
      controls regarding serum 25OHD levels or calculated vitamin D intake. Subjects
      sampled in the autumn had significantly higher levels of serum 25OHD than
      subjects sampled in the winter or spring. Serum 25OHD levels correlated to
      consumption of vitamin D-fortified lean milk (p = 0.001). CONCLUSION: The
      findings suggest no association between allergy and 25OHD levels in serum or
      vitamin D intake in adolescents. Serum 25OHD levels correlated to intake of
      vitamin D-fortified lean milk.

PMID- 25603835
TI  - Regulation of RYR2 by sarcoplasmic reticulum Ca(2+).
AB  - Ca(2+) is arguably the most important ion involved in the contraction of the
      heart. The cardiac ryanodine receptor (RyR2), the major Ca(2+) release channel
      located in the sarcoplasmic reticulum (SR) membrane, is responsible for releasing
      the bulk of Ca(2+) required for contraction. Moreover, RyR2 is also crucial for
      maintaining SR Ca(2+) homeostasis by releasing Ca(2+) from the SR when it becomes
      overloaded with Ca(2+) . During normal contraction, RyR2 is activated by
      cytosolic Ca(2+) , whereas during store overload conditions, the opening of RyR2
      is governed by SR Ca(2+) . Although the process of the cytosolic control of RyR2
      is well established, the molecular mechanism by which SR luminal Ca(2+) regulates
      RyR2 has only recently been elucidated and remains controversial. In addition to
      the activation of RyR2, SR luminal Ca(2+) also determines when the RyR2 channel
      closes. RyR2-mediated Ca(2+) release from the SR does not continue until the SR
      is completely depleted. Rather, it ceases when SR luminal Ca(2+) falls below a
      certain level. Given the importance of SR Ca(2+) , it is not surprising that the
      SR luminal Ca(2+) level is tightly controlled by SR Ca(2+) -buffering proteins.
      Consequently, the opening and closing of RyR2 is heavily influenced by the
      presence of such proteins, particularly those associated with RyR2, such as
      calsequestrin and the histidine-rich Ca(2+) -binding protein. These proteins
      appear to indirectly alter RyR2 activity by modifying the microdomain SR Ca(2+)
      level surrounding RyR2. 

PMID- 25603836
TI  - A Novel Assay for Easy and Rapid Quantification of Helicobacter pylori Adhesion.
AB  - BACKGROUND: Reducing adhesion of Helicobacter pylori to gastric epithelial cells
      could be a new way to counteract infections with this organism. We here present a
      novel method for quantification of Helicobacter pylori adhesion to cells.
      METHODS: Helicobacter pylori is allowed to adhere to AGS or MKN45g cells in a 96
      well microtiter plate. Then wells are added saponin, which lyses the cells
      without affecting the bacteria. After addition of alamarBlue((r)) (resazurin) and
      1- to 2-hour incubation, fluorescence measurements can be used to quantify the
      number of adherent bacteria. RESULTS: By use of the method, we demonstrate that
      adhesion of both a sabA and babA deletion mutant of H. pylori is significantly
      reduced compared to the wild type. CONCLUSION: The method offers a number of
      applications and may be used to compare the adherence potential of different
      strains of H. pylori to either cells or different materials or to screen for
      potential anti-adhesive compounds. The results presented here suggest that this
      easy and reproducible assay is well suited for quantitative investigation of H.
      pylori adhesion.

PMID- 25603837
TI  - The IVAIRE project--a randomized controlled study of the impact of ventilation on
      indoor air quality and the respiratory symptoms of asthmatic children in single
      family homes.
AB  - A randomized controlled trial was carried out to measure the impact of an
      intervention on ventilation, indoor air contaminants, and asthma symptoms of
      children. Eighty-three asthmatic children living in low-ventilated homes were
      followed over 2 years. Several environmental parameters were measured during the
      summer, fall, and winter. The children were randomized after Year 1 (43
      Intervention; 40 Control). The intervention included the installation of either a
      Heat Recovery Ventilator (HRV) or Energy Recovery Ventilator (ERV). During the
      fall and winter seasons, there was a significant increase in the mean ventilation
      rate in the homes of the intervention group. A statistically significant
      reduction in mean formaldehyde, airborne mold spores, toluene, styrene, limonene,
      and alpha-pinene concentrations was observed in the intervention group. There was
      no significant group difference in change in the number of days with symptoms per
      14 days. However, there was a significant decrease in the proportion of children
      who experienced any wheezing (>=1 episode) and those with >=4 episodes in the 12
      month period in the intervention group. This study indicates that improved
      ventilation reduces air contaminants and may prevent wheezing. Due to lack of
      power, a bigger study is needed. PRACTICAL IMPLICATIONS: Positive findings from
      this study include the fact that, upon recruitment, most of the single family
      homes with asthmatic children were already equipped with a mechanical ventilation
      system and had relatively good indoor air quality. However, the 8-h indoor
      guideline for formaldehyde (50 MUg/m3) was frequently exceeded and the
      ventilation rates were low in most of the homes, even those with a ventilation
      system. Both ERVs and HRVs were equally effective at increasing air exchange
      rates above 0.30 ACH and at preventing formaldehyde concentrations from exceeding
      the 50 MUg/m3 guideline during the fall and winter seasons. Furthermore, the ERVs
      were effective at preventing excessively low relative humidities in the homes.
      Based on observed difference of risk, intervention to increase ventilation in
      five sample homes and children would prevent 1 home to exceed the indoor air long
      term formaldehyde guideline and prevent 1 asthmatic child experiencing at least
      one episode of wheezing over a year.

PMID- 25603838
TI  - Open access behaviours and perceptions of health sciences faculty and roles of
      information professionals.
AB  - OBJECTIVE: This study sought to investigate the faculty's awareness, attitudes
      and use of open access, and the role of information professionals in supporting
      open access (OA) scholarly communication in Tanzanian health sciences
      universities. METHODS: A cross-sectional survey was conducted. Semi-structured
      interviews were conducted with 16 librarians, while questionnaires were
      physically distributed to 415 faculty members in all eight Tanzanian health
      sciences universities, with a response rate of 71.1%. RESULTS: The study found
      that most faculty members were aware about OA issues. However, the high level of
      OA awareness among faculty members did not translate into actual dissemination of
      faculty's research outputs through OA web avenues. A small proportion of
      faculty's research materials was made available as OA. Faculty were more engaged
      with OA journal publishing than with self-archiving practices. Senior faculty
      with proficient technical skills were more likely to use open access than junior
      faculty. Major barriers to OA usage were related to ICT infrastructure,
      awareness, skills, author-pay model, and copyright and plagiarism concerns.
      Interviews with librarians revealed that there was a strong support for promoting
      OA issues on campus; however, this positive support with various open access
      related tasks did not translate into actual action. It is thus important for
      librarians and OA administrators to consider all these factors for effective
      implementation of OA projects in research and academic institutions. CONCLUSION:
      This is the first comprehensive and detailed study focusing on the health
      sciences faculty's and librarians' behaviours and perceptions of open access
      initiatives in Tanzania and reveals findings that are useful for planning and
      implementing open access initiatives in other institutions with similar
      conditions.

PMID- 25603839
TI  - Hyperactive auditory processing in Williams syndrome: Evidence from auditory
      evoked potentials.
AB  - The neurophysiologic aberrations underlying the auditory hypersensitivity in
      Williams syndrome (WS) are not well defined. The P1-N1-P2 obligatory complex and
      mismatch negativity (MMN) response were investigated in 18 participants with WS,
      and the results were compared with those of 18 age- and gender-matched typically
      developing (TD) controls. Results revealed significantly higher amplitudes of
      both the P1-N1-P2 obligatory complex and the MMN response in the WS participants
      than in the TD controls. The P1-N1-P2 complex showed an age-dependent reduction
      in the TD but not in the WS participants. Moreover, high P1-N1-P2 complex was
      associated with low verbal comprehension scores in WS. This investigation
      demonstrates that central auditory processing is hyperactive in WS. The increase
      in auditory brain responses of both the obligatory complex and MMN response
      suggests aberrant processes of auditory encoding and discrimination in WS.
      Results also imply that auditory processing may be subjected to a delayed or
      diverse maturation and may affect the development of high cognitive functioning
      in WS. 

PMID- 25603840
TI  - Prophylaxis with FEIBA in paediatric patients with haemophilia A and inhibitors.
AB  - The benefits shown with factor VIII (FVIII) prophylaxis relating to joint health
      and quality of life (QoL) provide the rationale for FEIBA prophylaxis in
      haemophilia A patients with persistent FVIII inhibitors. FEIBA has previously
      shown efficacy in preventing bleeds in inhibitor patients who failed to respond
      to, or were ineligible for immune tolerance induction (ITI). The study examined
      the outcome of paediatric patients undergoing long-term FEIBA prophylaxis. A
      retrospective chart review included severe haemophilia A patients with persistent
      inhibitors aged <=13 years at the start of FEIBA prophylaxis. Baseline
      characteristics captured dose, frequency of prophylaxis, history of inhibitor
      development, including baseline titre, historical peak titre and history of ITI.
      Outcome measurements included annual bleed rate before and during FEIBA
      prophylaxis, joint status and school days missed. Sixteen cases of FEIBA
      prophylaxis from two centres are presented. The mean age of subjects at
      prophylaxis initiation was 7.5 +/- 3.6 years and median baseline inhibitor titre
      was 23 (range 3.1-170) BU. Prior to prophylaxis initiation, median annual joint
      bleeds among all patients was 4 (0-48), which dropped significantly after the
      first year of prophylaxis, to a median annual joint bleed rate of 1 (0-7; P =
      0.0179). Subsequent years (median = 9) of prophylaxis therapy demonstrated
      similarly low annual joint bleed rates. There were no life-threatening bleeds, no
      viral seroconversions or thrombotic events during FEIBA prophylaxis treatment.
      FEIBA prophylaxis was effective for preventing joint bleeds and subsequent joint
      damage, delaying arthropathy and improving outcomes in children with haemophilia
      A and inhibitors to FVIII, who failed or were ineligible for ITI. 

PMID- 25603841
TI  - Oscillatory rheology and creep behavior of barley beta-D-glucan concentrate
      dough: effect of particle size, temperature, and water content.
AB  - Small amplitude oscillatory rheology and creep behavior of beta-glucan
      concentrate (BGC) dough were studied as function of particle size (74, 105, 149,
      297, and 595 MUm), BGC particle-to-water ratio (1:4, 1:5, and 1:6), and
      temperature (25, 40, 55, 70, and 85  degrees C). The color intensity and protein
      content increased with decreasing particle size by creating more surface areas.
      The water holding capacity (WHC) and sediment volume fraction increased with
      increasing particle size from 74 to 595 MUm, which directly influences the
      mechanical rigidity and viscoelasticity of the dough. The dough exhibited
      predominating solid-like behavior (elastic modulus, G' > viscous modulus, G"). A
      discrete retardation spectrum is employed to the creep data to obtain retardation
      time and compliance parameters, which varied significantly with particle size and
      the process temperature. Creep tests exhibited more pronounced effect on dough
      behavior compared to oscillatory measurement. The protein denaturation
      temperature was insignificantly increased with particle fractions from 107 to 110
      degrees C. All those information could be helpful to identify the particle size
      range and WHC of BGC that could be useful to produce a beta-d-glucan enriched
      designed food. 

PMID- 25603845
TI  - Research on early warning of food security using a system dynamics model:
      evidence from Jiangsu province in China.
AB  - Analyzing the early warning of food security, this paper sets the self
      sufficiency rate as the principal indicator in a standpoint of supplement. It is
      common to use the quantitative methods to forecast and warning the insecurity.
      However, this paper considers more about the probable outcome when the government
      intervenes. By constructing the causal feedbacks among grain supplement, demand,
      productive input, and the policy factors to simulate the future food security in
      Jiangsu province, conclusions can be drawn as the following: (1) The situation of
      food security is insecure if the self-sufficiency rate is under 68.3% according
      to the development of system inertia. (2) it is difficult to guarantee the food
      security in Jiangsu just depending on the increase of grain sown area. (3) The
      valid solution to ensure the food security in Jiangsu is to improve the
      productivity. 

PMID- 25603846
TI  - Improvement of flavor and viscosity in hot and cold break tomato juice and sauce
      by peel removal.
AB  - Tomatoes are typically not peeled before being made into juice but the peels
      contain enzymes that affect the odor, flavor, and viscosity of the juice. The
      peels are removed in the finisher, but their presence during the break process
      may affect quality. Juice was processed from peeled and unpeeled tomatoes using
      hot or cold break. The juices were pasteurized by high temperature short time
      (HTST), low temperature long time (LTLT), or with a retort. The control samples
      were treated with 10% calcium chloride to stop enzymatic activity in the juice.
      Sauce was made from juice and the tomato products were analyzed for volatiles,
      color, viscosity, and by sensory. Cold break juice made with peel contained
      higher levels of some lipoxygenase-, carotenoid-, and amino acid-derived
      volatiles, than the juice made without peel. Because of the lack of enzyme
      activity, hot break juices had lower levels of these volatiles and there was no
      significant difference between hot break juices made with and without peel. CaCl2
      -treated and HTST juice had higher levels of most of the volatiles than LTLT,
      including the lipoxygenase-derived volatiles. The presence of peel produced a
      significant decrease in the viscosity of the cold break juice and sauce. There
      was no significant difference in the hue angle, total soluble solids, pH,
      titratable acidity, and vitamin C for most of the treatments. The texture,
      flavor, and overall liking of cold break juice made without peel were preferred
      over cold break juice made with peel whereas the color was less preferred.
      Between the sauces no significant differences in preference were obtained. 

PMID- 25603848
TI  - [Diagnostic and therapeutic strategies for severe alcoholic hepatitis].
AB  - Alcoholic hepatitis (AH) is defined as an acute hepatic manifestation resulting
      from heavy alcohol intake. Histologically, alcoholic steatohepatitis (ASH) is
      characterized by hepatocellular steatosis, inflammation, and fibrosis. Alcohol
      abstinence is the sine qua non of therapy for AH and, in the milder forms, is
      prerequisite to clinical recovery. Severe ASH may lead to multi-organ failure
      such as acute kidney injury and infection, which has a major impact on survival
      and thus should be closely monitored. Patients with severe ASH have a drastic
      short-term mortality of up to 40-50%. Specific therapies should be considered for
      patients with severe ASH at risk of early death. Corticosteroids are the standard
      of care for patients with severe ASH. When corticosteroids are contraindicated,
      pentoxifylline may be an alternative option. Steroid responsiveness should be
      evaluated on the basis of Lille score. Tactically, we should explore novel
      therapeutic targets to suppress inflammation based on cytokine profiles, promote
      hepatic regeneration, limit innate immune responses, and restore altered gut
      mucosal integrity in severe ASH.

PMID- 25603847
TI  - Early coupled up-regulation of interleukin-12 receptor beta-1 in CD8+ central
      memory and effector T cells for better clinical outcomes in liver transplant
      recipients.
AB  - This study aimed to investigate the role of initial priming of interleukin (IL)
      12 receptor beta-1 in CD8(+) central memory T cells (initial IL-12RTCM priming)
      and CCR7-negative subsets (CNS) in effector cell expansion and clinical outcome
      after living donor liver transplantation (LDLT). One hundred and six patients who
      underwent LDLT were classified into the following three groups according to
      hierarchical clustering of CD8(+) CD45 isoforms before LDLT: I, naive-dominant;
      II, effector memory-dominant; and III, effector-dominant. The pre-existing CD8(+)
      effector cells (TE ) and activated immune status increased progressively from
      group I to group II to group III. Groups I, II and III received tacrolimus
      (Tac)/glucocorticoid (GC) regimens. Eighteen group III recipients received
      Tac/mycophenolate mofetil (MMF) and were defined as group IV. Initial IL-12RTCM
      priming was slightly, moderately and markedly decreased in droups I, II, and III,
      respectively. Initial priming of IL-12Rbeta1 in CNS was decreased markedly in the
      three groups with marked decreases of TE , perforin and interferon (IFN)-gamma;
      all parameters were restored by up-regulation of IL-12Rbeta1(+) TCM through the
      self-renewal of TCM . The lag time required until coupled up-regulation of IL
      12Rbeta1 of TCM and CNS to above baseline was 12, 20 and 32 days in groups I, II
      and III, respectively. Inferior clinical outcomes were associated with increasing
      lag time. In contrast, the initial priming of IL-12Rbeta1 in TCM and CNS remained
      above baseline in group IV due to MMF-mediated increase of IL-12Rbeta1. Early
      coupled up-regulation of TCM and CNS leads to efficient TE differentiation and
      optimal clinical outcomes. 

PMID- 25603849
TI  - [Caustic injury of upper gastrointestinal tract: 20 year experience at a tertiary
      referral center].
AB  - BACKGROUND/AIMS: Caustic ingestion can cause severe injury to upper
      gastrointestinal tract. There were few studies about clinical characteristics and
      treatments of caustic injury in Korea. We investigated the changes in clinical
      features of caustic injury over the past 20 years including pattern of endoscopic
      mucosal injury and treatment modality. METHODS: This study was a retrospective
      review of medical records from patients with caustic injury from September 1993
      through December 2012. Patients were classified into two groups based on the year
      when caustic ingestion occurred: patients who visited the hospital from 1993 to
      2002 (early group) and patients who visited the hospital from 2003 to 2012 (late
      group). RESULTS: A total 140 patients were included (early group [n=50] vs. late
      group [n=90]). Annual number of caustic ingestions did not show decreasing
      tendency over the past 20 years. Alkali ingestion increased (20.0% vs. 65.6%,
      p<0.001) and cases with more than grade 2b of esophageal mucosal injury decreased
      (41.3% vs. 20.7%, p=0.012) in late group. There were no differences between two
      groups in sex, age, proportion of accidental ingestion, and
      systemic/gastrointestinal complications. Use of gastric lavage (p<0.01) and broad
      spectrum antibiotics (p=0.03) decreased in late group. However, there was no
      difference in use of steroid between two groups. CONCLUSIONS: In this study,
      overall caustic ingestion did not decrease and ingestion of alkali agents
      increased over the past 20 years. Tighter legislation on caustic agents is
      required and we need to be alert to the best management of caustic injury.

PMID- 25603850
TI  - Endoscopic ultrasonographic characteristics of gastric schwannoma distinguished
      from gastrointestinal stromal tumor.
AB  - BACKGROUND/AIMS: Gastric schwannoma (GS), a rare neurogenic mesenchymal tumor, is
      usually benign, slow-growing, and asymptomatic. However, GS is often misdiagnosed
      as gastrointestinal stromal tumors (GIST) on endoscopic and radiological
      examinations. The purpose of this study was to evaluate EUS characteristics of GS
      distinguished from GIST. METHODS: A total of 119 gastric subepithelial lesions,
      including 31 GSs and 88 GISTs, who were histologically identified and underwent
      EUS, were enrolled in this study. We evaluated the EUS characteristics, including
      location, size, gross morphology, mucosal lesion, layer of origin, border,
      echogenic pattern, marginal halo, and presence of an internal echoic lesion by
      retrospective review of the medical records. RESULTS: GS patients comprised nine
      males and 22 females, indicating female predominance. In the gross morphology
      according to Yamada's classification, type I was predominant in GS and type III
      was predominant in GIST. In location, GSs were predominantly located in the
      gastric body and GISTs were predominantly located in the cardia or fundus. The
      frequency of 4th layer origin and isoechogenicity as compared to the echogenicity
      of proper muscle layer was significantly more common in GS than GIST. Although
      not statistically significant, marginal halo was more frequent in GS than GIST.
      The presence of an internal echoic lesion was significantly more common in GIST
      than GS. CONCLUSIONS: The EUS characteristics, including tumor location, gross
      morphology, layer of origin, echogenicity in comparison with the normal muscle
      layer, and presence of an internal echoic lesion may be useful in distinguishing
      between GS and GIST.

PMID- 25603851
TI  - [Randomized controlled trial of sodium phosphate tablets versus 2 L polyethylene
      glycol solution for bowel cleansing prior to colonoscopy].
AB  - BACKGROUND/AIMS: Performance of polyethylene glycol solution (PEG) is often
      unsatisfactory as bowel preparation agent for colonoscopy. In order to provide
      equivalent efficacy with better patient tolerance, sodium phosphate tablet (SPT)
      has been developed. This study was carried out to compare the efficacy and
      compliance of two bowel preparation methods: PEG with ascorbic acid (PEGA) vs.
      SPT preparation. METHODS: A multicenter, randomized controlled trial was
      performed. Primary efficacy variable was overall quality of colon cleansing
      assessed by Boston bowel preparation scale (BBPS) during colonoscopy. Patient's
      satisfaction and adverse events were evaluated by means of symptom questionnaire
      completed by each patient immediately before colonoscopy. RESULTS: A total of 189
      patients were randomly assigned to undergo pre-colonoscopic bowel preparation
      with either SPT (n = 96) or PEGA (n = 93). Overall BBPS score was 8.3 +/- 1.12 in
      the SPT group and 8.4 +/- 0.96 in the PEGA group (p = 0.441). Among the 189
      patients, 90 had polyps (47.6%) and 50 had adenomas (26.5%). The polyp/adenoma
      detection rate was 54.2% (n = 52)/27.1% (n = 26) for SPT group and 40.9% (n =
      38)/25.8% (n = 24) for PEGA group (p = 0.079 and 0.790, respectively). More
      number of patients were unable to take the prescribed dose of PEGA compared with
      the SPT regimen (8.6% vs. 2.0%, p = 0.045). Overall satisfaction score was 7.9 +/
      1.63 in the SPT group and 7.4 +/- 1.53 in the PEGA group (p = 0.022).
      CONCLUSIONS: Degree of colon preparation, polyp/adenoma detection rate and
      adverse effect were similar between SPT group and PEGA group. Patient compliance
      and satisfaction were greater in the SPT group.

PMID- 25603852
TI  - [Efficacy of tenofovir-based rescue therapy for patients with drug-resistant
      chronic hepatitis B].
AB  - BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the
      management of drug-resistant chronic hepatitis B. However, it remains unclear
      whether TDF-nucleoside analogue combination therapy provides better outcomes than
      TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with
      that of TDF-nucleoside analogue combination therapy in patients with drug
      resistant chronic hepatitis B. METHODS: This retrospective cohort study included
      76 patients receiving TDF-based rescue therapy for more than 12 months.
      Suboptimal response was defined as serum HBV-DNA level of > 60 IU/mL during prior
      rescue therapy. Multi-drug resistance was defined as the presence of two or more
      drug resistance-related mutations confirmed by mutation detection assay. The
      relationship between baseline characteristics and virologic response (HBV DNA <
      20 IU/mL) at 12 months were evaluated using logistic regression analysis.
      RESULTS: Fifty-five patients (72.4%) were suboptimal responders to prior rescue
      therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%)
      received combination therapy with nucleoside analogues. Virologic response at 12
      months was not significantly different between the TDF monotherapy group and TDF
      nucleoside analogue combination therapy group (p = 0.098). The serum HBV DNA
      level was reduced to -4.49 +/- 1.67 log10 IU/mL in the TDF monotherapy group and
      to -3.97 +/- 1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy
      group at 12 months (p = 0.18). In multivariate analysis, female sex (p = 0.032),
      low baseline HBV-DNA level (p = 0.013), and TDF monotherapy (p = 0.046) were
      predictive factors for virologic response at 12 months. CONCLUSIONS: TDF
      monotherapy showed similar efficacy to that of TDF-nucleoside analogue
      combination therapy in patients with drug-resistant chronic hepatitis B.

PMID- 25603853
TI  - [Gastric perforation caused by primary gastric diffuse large B cell lymphoma].
AB  - Spontaneous gastric perforation is a rare complication of gastric lymphoma that
      is potentially life threatening since it can progress to sepsis and multi-organ
      failure. Morbidity also increases due to prolonged hospitalization and delay in
      initiating chemotherapy. Therefore prompt diagnosis and appropriate treatment is
      critical to improve prognosis. A 64-year-old man presented to the emergency
      department with severe abdominal pain. Chest X-ray showed free air below the
      right diaphragm. Abdominal CT scan also demonstrated free air in the peritoneal
      cavity with large wall defect in the lesser curvature of gastric lower body.
      Therefore, the patient underwent emergency operation and primary closure was
      done. Pathologic specimen obtained during surgery was compatible to diffuse large
      B cell lymphoma. Fifteen days after primary closure, the patient received
      subtotal gastrectomy and chemotherapy was initiated after recovery. Patient is
      currently being followed-up at outpatient department without any particular
      complications. Herein, we report a rare case of gastric lymphoma that initially
      presented as peritonitis because of spontaneous gastric perforation.

PMID- 25603854
TI  - A case of autoimmune hepatitis combined with Graves' disease.
AB  - A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg
      during a period of 2 weeks. Laboratory tests showed elevated levels of liver
      enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL);
      negative for hepatitis virus infection; elevated serum levels of triiodothyronine
      (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of
      thyroid stimulating hormone (TSH, <0.025 MUIU/mL); and positive for thyroid
      stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy
      findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral
      steroid therapy was started with 60 mg of prednisolone under the impression of
      AIH associated with Graves' disease. After a week of steroid therapy, the
      clinical manifestation showed significant improvement, with normalization of both
      liver and thyroid functions. Diagnosis of the liver condition of patients who
      present with hyperthyroidism and liver dysfunction is important, so that
      appropriate therapy can be promptly initiated.

PMID- 25603855
TI  - A case of nodular regenerative hyperplasia of the liver combined with toxic
      hepatitis.
AB  - Nodular regenerative hyperplasia (NRH) is an uncommon liver condition
      characterized by diffuse transformation of the hepatic parenchyma into
      regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal
      hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative
      nodules. Underlying diseases or certain drugs may also be the cause of NRH. This
      condition is often underdiagnosed as the patients remain asymptomatic until
      development of portal hypertension, and histopathologic confirmation by liver
      biopsy is the only way of making a definite diagnosis. The management mainly
      involves prevention and treatment of the complications of portal hypertension.
      The frequency of diagnosis of NRH has increased rapidly in recent years, however,
      only a few cases have been reported in Korea. Here, we report on a case of NRH of
      the liver combined with toxic hepatitis.

PMID- 25603856
TI  - Osler-Weber-Rendu disease presenting as recurrent portosystemic encephalopathy in
      a 75-year-old female patient.
AB  - Osler-Weber-Rendu disease is a rare autosomal dominant disorder of fibrovascular
      tissues, characterized by a classic triad of mucocutaneous telangiectasias,
      recurrent hemorrhages, and a familial occurrence. Portosystemic encephalopathy in
      a patient with Osler-Weber-Rendu disease is rare, but we experienced a case
      presenting with recurrent portosystemic encephalopathy in Osler-Weber-Rendu
      disease. We report on a case of a 75-year-old female presenting with an altered
      mentality. Initial studies including brain imaging study did not reveal any
      specific cause for her mental status. She was diagnosed with the rare disease
      after a series of tests and received conservative treatment. Her neurological
      status recovered fully without complication after conservative treatment and she
      was discharged after 18 hospital days. This case demonstrated an extremely rare
      case of Osler-Weber-Rendu disease presenting as portosystemic encephalopathy
      treated successfully with conservative treatment. For patients who have shown
      hepatic encephalopathy without a definite cause, we recommend evaluation for the
      possibility of Osler-Weber-Rendu disease. Conservative treatment based on
      treatment of advanced liver cirrhosis could be an alternative solution.

PMID- 25603857
TI  - Tumor necrosis-initiated complement activation stimulates proliferation of
      medulloblastoma cells.
AB  - OBJECTIVE AND DESIGN: We sought to determine the effect of necrosis-induced
      activation of the complement protein C3 in medulloblastoma. MATERIALS/METHODS:
      Twelve medulloblastoma surgical specimens were evaluated for complement
      activation using immunohistochemistry, with H&E stains performed on adjacent
      tissue sections to determine the relationship of complement activation to
      necrotic tissue. Flow cytometry and Western blot were performed on three
      established medulloblastoma lines and one surgically-procured cell culture to
      determine expression of C3a receptor (C3aR) in medulloblastoma. In vitro
      proliferation of siRNA C3aR knockdown cells was compared to that of control siRNA
      cells with cell line Daoy. RESULTS: Three surgical specimens were found to have
      necrosis on H&E sections. In each case, iC3b staining was identified on adjacent
      sections, limited to the necrotic region. In no case did necrosis occur without
      iC3b staining on adjacent sections. C3aR protein was demonstrated on both the
      three established cell lines and on the surgical culture. Proliferation assays of
      Daoy cells with siRNA knockdown vs. control siRNA revealed significantly reduced
      proliferation at 72 h (p = 0.001). CONCLUSIONS: Necrosis is associated with
      complement activation in medulloblastoma. Medulloblastoma cells express C3aR, and
      siRNA-mediated knockdown of C3aR inhibits proliferation of these cells in vitro.

PMID- 25603858
TI  - NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via
      Neuroinflammation.
AB  - BACKGROUND: Evidence from both clinical and experimental research indicates that
      the immune-brain interaction plays a pivotal role in the pathophysiology of
      depression. A multi-protein complex of the innate immune system, the NLRP3
      inflammasome regulates cleavage and secretion of proinflammatory cytokine
      interleukin-1beta. The inflammasome detects various pathogen-associated molecule
      patterns and damage-associated molecule patterns, which then leads to a series of
      immune-inflammatory reactions. METHODS: To explore the role of inflammasome
      activation in the underlying biological mechanisms of depression, we established
      a mouse model of depression with unpredictable chronic mild stress. RESULTS: Mice
      subjected to chronic mild stress for 4 weeks had significantly higher serum
      corticosterone levels, serum interleukin-1beta levels, and hippocampal active
      interleukin-1beta protein levels. They also displayed depressive-like symptoms,
      including decreased sucrose preference and increased immobility time. Moreover,
      the hippocampi of chronic mild stress-exposed mice had significantly higher
      activity of caspase-1, which accompanied by higher protein levels of NLRP3 and
      the apoptotic speck-containing protein with a card. Pretreatment with the NLRP3
      inflammasome inhibitor VX-765 decreased serum and hippocampal levels of
      interleukin-1beta protein and significantly moderated the depressive-like
      behaviors induced by chronic mild stress. CONCLUSIONS: These data suggest the
      NLRP3 inflammasome mediates stress-induced depression via immune activation.
      Future procedures targeting the NLRP3 inflammasome may have promising effects in
      the prevention and treatment of depression.

PMID- 25603859
TI  - Glutamatergic neurometabolites in clozapine-responsive and -resistant
      schizophrenia.
AB  - BACKGROUND: According to the current schizophrenia treatment guidelines, 3 levels
      of responsiveness to antipsychotic medication exist: those who respond to first
      line antipsychotics, those with treatment-resistant schizophrenia who respond to
      clozapine, and those with clozapine-resistant or ultra-treatment resistant
      schizophrenia. Proton magnetic resonance spectroscopy studies indicate that
      antipsychotic medication decreases glutamate or total glutamate + glutamine in
      the brains of patients with schizophrenia and may represent a biomarker of
      treatment response; however, the 3 levels of treatment responsiveness have not
      been evaluated. METHODS: Proton magnetic resonance spectroscopy spectra were
      acquired at 3 Tesla from patients taking a second generation non-clozapine
      antipsychotic (first-line responders), patients with treatment-resistant
      schizophrenia taking clozapine, patients with ultra-treatment resistant
      schizophrenia taking a combination of antipsychotics, and healthy comparison
      subjects. RESULTS: Group differences in cerebrospinal fluid-corrected total
      glutamate + glutamine levels scaled to creatine were detected in the dorsolateral
      prefrontal cortex [df(3,48); F = 3.07, P = .04, partial eta(2) = 0.16] and the
      putamen [df(3,32); F = 2.93, P = .05, partial eta(2) = 0.22]. The first-line
      responder group had higher dorsolateral prefrontal cortex total glutamate +
      glutamine levels scaled to creatine than those with ultra-treatment resistant
      schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family
      wise error-corrected]. Those with treatment-resistant schizophrenia had higher
      total glutamate + glutamine levels scaled to creatine in the putamen than the
      first-line responders (mean difference = 0.31, standard error = 0.12, P = .05,
      family-wise error-corrected) and those with ultra-treatment-resistant
      schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family
      wise error-corrected). CONCLUSIONS: Total glutamate + glutamine levels scaled to
      creatine in the putamen may represent a marker of response to clozapine. Future
      studies should investigate glutamatergic anomalies prior to clozapine initiation
      and following successful treatment.

PMID- 25603860
TI  - The N-methyl-D-aspartate receptor as a neurobiological intersection between
      bipolar disorder and alcohol use: a longitudinal mismatch negativity study.
AB  - BACKGROUND: Comorbid risky alcohol use in bipolar disorder (BD) is recognized for
      its high prevalence and clinical relevance, though understanding of its
      neurobiological underpinning is limited. The N-methyl-D-aspartate (NMDA) receptor
      has recognized alterations in BD and is a major site of ethanol's effects in the
      brain. The present study aimed to examine the NMDA receptor system in adolescents
      and young adults with BD by evaluating the longitudinal changes in a robust
      marker of NMDA function, mismatch negativity (MMN), in relation to changes in
      alcohol use patterns. METHODS: Forty-six BD patients (aged 16-30) were recruited
      at baseline and 59% (n = 27) returned for follow-up 17.9 +/- 7.3 months later. At
      both time-points a two-tone, passive, duration-deviant MMN paradigm was conducted
      and alcohol measures were collected. Pearson's correlations were performed
      between changes in MMN amplitudes and changes in alcohol use. Multiple regression
      was used to assess whether MMN amplitudes at baseline could predict alcohol use
      at follow-up. RESULTS: Reduction in risky drinking patterns was associated with
      increased temporal MMN and decreased fronto-central MMN. Larger temporal MMN at
      baseline was a significant predictor of greater alcohol use at follow-up.
      CONCLUSIONS: Results suggest risky alcohol use in BD may further compound pre
      existing NMDA receptor abnormalities and, importantly, reducing alcohol use early
      in stages of illness is associated with changes in MMN. This highlights the
      importance of monitoring alcohol use from first presentation. In addition,
      preliminary results present an exciting potential for utility of MMN as a
      neurobiological marker used to determine risk for alcohol misuse in BD.

PMID- 25603863
TI  - Mycobacterial proteomics: analysis of expressed proteomes and post-translational
      modifications to identify candidate virulence factors.
AB  - The Mycobacterium tuberculosis bacillus has a number of unique features that make
      it a particularly effective human pathogen. Although genomic analysis has added
      to our current understanding of the molecular basis by which M. tuberculosis
      damages its host, proteomics may be better suited to describe the dynamic
      interactions between mycobacterial and host systems that underpin this disease.
      The M. tuberculosis proteome has been investigated using proteomics for over a
      decade, with increasingly sophisticated mass spectrometry technology and
      sensitive methods for comparative proteomic profiling. Deeper coverage of the M.
      tuberculosis proteome has led to the identification of hundreds of putative
      virulence determinants, as well as an unsurpassed coverage of post-translational
      modifications. Proteomics is therefore uniquely poised to contribute to our
      understanding of this pathogen, which may ultimately lead to better management of
      the disease. 

PMID- 25603861
TI  - Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of
      Delayed Rewards in Methamphetamine Dependence.
AB  - BACKGROUND: Individuals with substance use disorders typically exhibit a
      predilection toward instant gratification with apparent disregard for the future
      consequences of their actions. Indirect evidence suggests that low dopamine D2
      type receptor availability in the striatum contributes to the propensity of these
      individuals to sacrifice long-term goals for short-term gain; however, this
      possibility has not been tested directly. We investigated whether striatal D2/D3
      receptor availability is negatively correlated with the preference for smaller,
      more immediate rewards over larger, delayed alternatives among research
      participants who met DSM-IV criteria for methamphetamine (MA) dependence.
      METHODS: Fifty-four adults (n = 27 each: MA-dependent, non-user controls)
      completed the Kirby Monetary Choice Questionnaire, and underwent positron
      emission tomography scanning with [(18)F]fallypride. RESULTS: MA users displayed
      steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor
      availability (p < 0.0005) than controls. Discount rate was negatively correlated
      with striatal D2/D3 receptor availability, with the relationship reaching
      statistical significance in the combined sample (r = -0.291, p = 0.016) and among
      MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179,
      p = 0.185); the slopes did not differ significantly between MA users and controls
      (p = 0.5). CONCLUSIONS: These results provide the first direct evidence of a link
      between deficient D2/D3 receptor availability and steep temporal discounting.
      This finding fits with reports that low striatal D2/D3 receptor availability is
      associated with a higher risk of relapse among stimulant users, and may help to
      explain why some individuals choose to continue using drugs despite knowledge of
      their eventual negative consequences. Future research directions and therapeutic
      implications are discussed.

PMID- 25603865
TI  - Erratum.

PMID- 25603864
TI  - Proteomics: in pursuit of effective traumatic brain injury therapeutics.
AB  - Effective traumatic brain injury (TBI) therapeutics remains stubbornly elusive.
      Efforts in the field have been challenged by the heterogeneity of clinical TBI,
      with greater complexity among underlying molecular phenotypes than initially
      conceived. Future research must confront the multitude of factors comprising this
      heterogeneity, representing a big data challenge befitting the coming informatics
      age. Proteomics is poised to serve a central role in prescriptive therapeutic
      development because it offers an efficient endpoint within which to assess post
      TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and
      the particular importance of temporal profiling in defining biochemical sequences
      and guiding therapeutic development. Finally, we offer perspective on repurposing
      biofluid proteomics to develop theragnostic assays with which to prescribe,
      monitor and assess pharmaceutics for improved translation and outcome for
      patients with TBI. 

PMID- 25603866
TI  - [99mTc-octreotide receptor scintigraphy in NCI-H446 small cell lung cancer nude
      mice model].
AB  - BACKGROUND: For highly aggressive small cell lung cancer (SCLC), early diagnosis
      is important for its prognosis, but the current inspection methods are more
      limited, with poor specificity of the traditional imaging methods, and the high
      cost of PET/CT, difficult to popularization and application. SCLC is kind of
      neuroendocrine tumors, high expression of somatostatin receptors, which is the
      cornerstone of its early molecular imaging diagnosis. The aim of this study is to
      observe the biodistribution and metabolism of 99mTc-octreotide in normal and the
      human SCLC bearing nude mice. METHODS: Dynamic and static scintigraphy at 0.5 h,
      2 h, 3 h, 4 h were performed in both normal and tumor bearing nude mice after
      intravenous injection of 99mTc-octreotide. The technique of drawing region of
      interest (ROI) was used to obtain the averaged pixel counts and the activity-time
      (A-T) curve of brain, heart, lung, liver, kidney, tumor, respectively. RESULTS: 1
      The biodistribution study in normal nude mice showed highest uptake in kidney and
      liver, lower in lung and heart, lowest in brain. Most 99mTc-octreotide was
      excreted via kidney. 2 All tumors were displayed clearly at 3 h postinjection of
      99mTc-octreotide. The averaged T/N ratio at 0.5 h, 2 h, 3 h, 4 h postinjection of
      99mTc-octreotide was 1.163 +/- 0.03, 2.08 +/- 0.12, 3.03 +/- 0.23, 2.689 +/-
      0.31, respectively (F=51.69, P<0.000,1). The radioactivity of tumor was lower
      than liver, and similar with the lung. The curve of tumor showed a radioactivity
      peak at 2 min-3 min postinjection. CONCLUSIONS: 99mTc-octreotide receptor imaging
      on nude mice bearing SCLC shares high positive rate, especially at 3 h
      postinjection.

PMID- 25603867
TI  - [Expression of TLR5 in different types of non-small cell lung cancer cell lines
      and its activation mechanism].
AB  - BACKGROUND: It has been proven that toll-like receptor 5 (TLR5) plaied an
      important role in the development of tumor. In our previous study, we found that
      the expression of TLR5 was remarkably higher in non-small cell lung cancer
      (NSCLC) tissues than that in normal tissues, but the activation of TLR5 signaling
      pathway in NSCLC was still unknown. The aim of this study is to investigate the
      expression of TLR5 in different types of NSCLC cell lines, and analyze the
      activity of the signaling pathway after stimulated by its specific exogenous
      ligand flagellin. METHODS: The TLR5 protein was detected by immunofluorescence
      and Western blot in three kinds of NSCLC cell lines, and the TLR5 mRNA was
      detected by RT-PCR. Select the cell line of TLR5 highest expression as the
      research object, and select the suitable concentration of flagellin. NF-kappaB
      luciferase activity was detected to validate the TLR5 activation pathway through
      inhibitory signaling pathways by 0 MUg/mL, 0.01 MUg/mL, 0.1 MUg/mL, 1 MUg/mL, 10
      MUg/mL TLR5 antibody. The chosen cell line was transfected by TLR5 shRNA plasmid,
      and p-IKBalpha, IKBalpha, p-ERK1/2, ERK1/2 and p-JNK of untrasfected and
      transfected cells were detected in the activity of TLR5 signaling pathway by
      Western blot at 0 min, 10 min, 30 min and 60 min, respectively. RESULTS: The
      expression of TLR5 was the highest in the lung adenocarcinoma cell line SPC-A-1
      by immunofluorescence, mainly expressed on the cell membrane. NF-kappaB
      luciferase activity of SPC-A-1 cells was the highest, and the activity was
      increased in a dose-dependent manner. 0.1 MUg/mL flagellin could significantly
      increase the NF-kappaB luciferase activity (P<0.05), while its activity could be
      inhibited by the TLR5 antibody in a negative correlation. Treated by 0.1 MUg/mL
      flagellin, compared with that of 0 min group, the levels of p-IKBalpha, p-ERK1/2,
      p-JNK of SPC-A-1 cells increased significantly after 10 min, reached the peak at
      30 min, and declined at 60 min (P<0.05). Compared with that of 10 min and 60 min
      group, the levels of p-IKBalpha, p-ERK1/2, p-JNK significantly increased at 30
      min (P<0.05). While the levels of IKBalpha, ERK1/2 at 0 min, 10 min, 30 min and
      60 min had no significant changes (P>0.05). SPC-A-1 cells transfected TLR5-shRNA
      were also stimulated by flagellin (0.1 MUg/mL). At 0 min, 10 min, 30 min and 60
      min, p-IKBalpha and p-JNK proteins could not be detected, and the levels of
      IKBalpha and ERK1/2 had no significant changes (P>0.05), but the levels of p
      ERK1/2 significantly increased as time went on (P<0.05). CONCLUSIONS: Exogenous
      ligand flagellin can activate TLR5 protein in NSCLC cell lines and initiate
      downstream signaling pathways. It may be relative to the development of NSCLC.

PMID- 25603868
TI  - [Molecular epidemiology study in Xuanwei: the relationship among ?coal type,
      genotype and lung cancer risk].
AB  - BACKGROUND: It has been proven that the lung cancer mortality rate in Xuanwei
      County, China was among the highest in the country and has been associated with
      exposure to indoor smoky coal emissions that contain high levels of polycyclic
      aromatic hydrocarbons. This risk may be modified by variation in genetic
      polymorphisms and coal subtypes. Our objective was to use molecular
      epidemiological techniques to investigate the relationship among genetic
      polymorphisms, coal subtype and lung cancer risk in Xuanwei County. METHODS: On
      the basis of two population-based case-control studies in residents of Xuanwei
      County, China, questionnaires covering demographic information, smoking history,
      family and personal medical history, and information on other variables were
      administered and buccal cells and sputum samples were collected separately from
      each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1
      superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs
      were used to estimate the association between genotypes, coal subtypes and lung
      cancer risk factors by conditional Logistic regression using Statistical Analysis
      Software. RESULTS: Compared with subjects who using smokeless coal or wood, smoky
      coal use was statistically significantly associated with lung cancer risk
      (OR=7.7, 95%CI: 4.5-13.3). There was marked heterogeneity in risk estimates for
      specific subtypes of smoky coal. Estimates were highest for coal from the Laibin
      (OR=24.8), Longtan (OR=11.6) and Baoshan (OR=6.0) coal types, and lower for coal
      from other types; the risk within the same subtype of coal in male and female
      were similar. The GSTM1-null genotype, the AKR1C3 (Ex1-70C>G), OGG1 (Ex6-315C>G)
      genotypes were closely associated with increased risk of lung cancer in Xuanwei
      County, and their odds ratios (95%CI) were 2.3 (1.3-4.2), 1.8 (1.0-3.5) and 1.9
      (1.1-3.3), respectively. Compared to subjects who with GSTM1-positive and used
      less than 130 tons of smoky coal during their lifetime, higher risks were closely
      associated with GSTM1-null and heavier users (>=130 tons), with the OR was 4.9
      (95%CI: 1.3-18.2) and 2.7 (95%CI: 1.0-7.4) for female and male, respectively.
      However, higher risks were only found within female for AKR1C3 (Ex1-70C>G) and
      OGG1 (Ex6-315C>G), with OR (95%CI)=12.9 (2.2-107.8) and 5.7 (1.1-34.2),
      respectively. CONCLUSIONS: Lung cancer risks varied among coal subtypes; however,
      risks were similar between men and women exposed to the same type of coal. The
      GSTM1-null genotype may enhance susceptibility to air pollution from indoor smoky
      coal combustion emissions. AKR1C3 and OGG1 genotypes were significantly
      associated with higher risk of lung cancer, especially among heavily exposed
      women.

PMID- 25603869
TI  - [Clinical significance of mutant p53 protein expression in lung adenocarcinoma].
AB  - BACKGROUND: P53 is a tumor protein that acts as a tumor suppressor. The mutation
      of P53 may cause loss of tumor suppressor functions and gain of functions
      favoring cellular proliferation and apoptosis inhibition. The clinical
      implications of the tumor protein P53 gene (TP53) mutation in lung adenocarcinoma
      are indefinite. The aim of this study is to explore the clinical significance of
      the mutant P53 protein expression in lung adenocarcinoma tissues. METHODS: The
      clinicopathological data of 120 lung adenocarcinoma patients who underwent
      surgery were retrospectively analyzed. The mutant P53 protein expression was
      detected using the immunohistochemical method. Furthermore, the relationship
      between the mutant P53 expression and the clinicopathological parameters was
      analyzed using the Chi-square test, whereas that between the mutant P53
      expression and overall survival was estimated using the Kaplan-Meier method and
      Cox regression model. RESULTS: The mutant P53 protein expression rate was 63.3%.
      Accordingly, the mutant P53 expression was significantly associated with tumor
      size (P=0.041) and clinicopathological stage (P=0.025). On the one hand, a
      univariate survival analysis showed that tumor size (P=0.031), lymph node
      metastasis (P<0.001), clinicopathological stage (P<0.001), and mutant P53
      expression (P=0.038) were associated with overall survival. On the other hand, a
      multivariate survival analysis showed that lymph node metastasis (P=0.014) was an
      independent poor prognostic factor for overall survival. CONCLUSIONS: Patients
      with lung adenocarcinoma with mutant TP53 had a poor outcome. Accordingly, the
      mutant P53 protein may serve as a molecular prognosis marker for lung
      adenocarcinoma patients.

PMID- 25603870
TI  - [Significance of detection of serum carbonic anhydrase IX in the diagnosis of
      lung cancer].
AB  - BACKGROUND: Carbonic anhydrase IX (CAIX) is a transmembrane protein involved in
      the metabolism of tumor cells. CAIX is expressed in only a few normal tissues but
      is overexpressed in various tumor types. The aim of this study is to detect the
      serum CAIX level of patients with lung cancer, evaluate the significance of CAIX
      detection in the diagnosis of lung cancer, and analyze the serum CAIX level among
      different pathological types and TNM stages of lung cancer. METHODS: Forty-seven
      patients with lung cancer and 31 healthy subjects were selected to participate in
      this study. Serum CAIX level was examined through enzyme-linked immunosorbent
      assay (ELISA). The subjects were grouped according to histological type and TNM
      staging, and serum CAIX level was compared among the groups. With pathological
      diagnosis as the gold standard, receiver operating characteristic curve of the
      serum CAIX level was established for the diagnosis of lung cancer. RESULTS: The
      CAIX serum level was significantly higher in patients with lung cancer than that
      in the healthy group (P<0.001). The serum CAIX level in patients with squamous
      cell carcinoma and small cell carcinoma was also significantly higher than that
      in patients with adenocarcinoma. No statistically significant differences were
      observed in the serum CAIX level between I+II and III+IV staging. The AUC of
      serum CAIX level was 0.961. At a threshold level of 115.115 pg/mL, sensitivity
      and specificity were 95.7% and 90.3%, respectively. CONCLUSIONS: Detection of the
      serum CAIX level through ELISA exhibits high sensitivity and specificity and is
      important for the diagnosis of lung cancer.

PMID- 25603871
TI  - [Advances of mediastinal lymph node metastasis and the extent of lymph node
      ?dissection in patients with stage T1 non-small cell lung cancer].
AB  - Lung cancer ranks the first position in morbidity and mortality among all
      malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80%
      of all lung malignancies. Surgical resection is still the current major treatment
      method for early stage NSCLC. Lymph node stages together with the extent of lymph
      node dissection directly affect the prognosis. The site of primary lung carcinoma
      may affect the route and status of lymph node metastasis. Up to now, anatomical
      lobectomy and mediastinal lymph node dissection is deemed to be the standard
      surgical treatment for NSCLC. However, it is still controversial in the extent of
      lymph node dissection for T1 NSCLC. More and more surgeons intend to perform
      selective mediastinal lymph node dissection instead of complete mediastinal lymph
      node dissection for T1 NSCLC in recent years. 

PMID- 25603872
TI  - [Advances on driver oncogenes of non-small cell lung cancer].
AB  - Adenocarcinoma and squamous cell carcinoma are the most common histological types
      of non-small cell lung cancer (NSCLC). Several molecular alterations have been
      defined as "driver oncogenes" responsible for both the initiation and maintenance
      of the malignancy. With next-generation sequencing (NGS) which having multiple
      and high-throughput genotyping is wildly used and promoted, make the detection of
      patients gene composition from a tiny tumor biopsy specimens become possible,
      initiate the clinical studies based on the genetic characteristics, and promote
      the progress of molecular typing in NSCLC. So far, about 60% of lung
      adenocarcinoma has been found harbouring driver oncogenes, the rate of lung
      squamous cell carcinoma driven genes detection has gradually improved, in which
      epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK),
      fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol 3-kinase
      catalytic subunit alpha (PIK3CA) and so on plays important roles. The currently
      effective targeted therapies is mainly used against EGFR, ALK, etc. In this
      review, we will report the mainly advances on some latest driver mutations of
      NSCLC. 

PMID- 25603873
TI  - [Tumor microenvironment--the critical element of tumor metastasis].
AB  - Metastasis is the main reason for the failure of cancer therapy and the death of
      patients. The molecular mechanism is complex, involving the change of multi-step,
      multi-stage and multi-gene. As the survival places of tumor cells, the tumor
      microenvironment plays a crucial role in tumor metastasis. Therefore, the study
      of the dynamic relationship between the tumor microenvironment and tumor
      metastasis, to clarify the molecular mechanisms in the metastasis process is the
      key point to inhibit the tumor metastasis. 

PMID- 25603874
TI  - [Interaction between microRNAs and OCT4].
AB  - Octamer-binding transcription factor 4 (OCT4) belongs to the POU-homeodomain
      family of transcription factors and binds to an octamer motif, ATGCAAAT. OCT4 is
      the key transcription factor that is involved in the maintenance of pluripotency
      and self-renewal in undifferentiated embryonic stem (ES) cells. OCT4 has been
      reported to be overexpressed in various cancers including lung, germ cell tumors,
      breast, cervix, prostate, gastric, liver, and ovarian cancer. MicroRNAs (miRNAs),
      small non-coding RNAs, modulate mRNA expression through base pairing between seed
      sequences in miRNA and complementary sequences of the target mRNA, thereby
      destabilizing mRNA and/or inhibiting protein synthesis. Several miRNAs have been
      demonstrated to regulate stemness factors such as OCT4, NANOG, SOX2 and KLF4 in
      cancer cells, thereby modulating the proliferation, apoptosis, differentiation,
      drug resistance and immunity of cancer cells. 

PMID- 25603876
TI  - 3D transesophageal echocardiography is a decision-making tool for the management
      of cardiogenic shock following a large postinfarction ventricular defect.
AB  - Postinfarction ventricular septal defect (PIVSD) is a devastating mechanical
      complication following acute myocardial infarction. The management of this
      pathology is quite challenging, especially in case of complicated cardiogenic
      shock. The difficulties lie in the timing and type of intervention. Debates exist
      with regard to immediate versus deferring repair, as well as open repair versus
      percutaneous closure. The anatomic characteristics and hemodynamic consequence of
      PIVSD are important elements determining which strategy to adopt, since large
      septal defect (>15 mm) cannot be appropriately treated by percutaneous occluder
      devices limiting by their available size, while compromised hemodynamics usually
      require emergent repair or mechanical support "bridging to surgery". Herein, we
      report our experience of successful management of a case of cardiogenic shock
      complicating large PIVSD (38 mm) by delayed surgical repair bridged with
      Extracorporeal Membrane Oxygenation (ECMO) during 7 days. We emphasize the
      importance of 3-dimensional transesophageal echocardiography as a decision-making
      tool. 

PMID- 25603877
TI  - National trends in hospital length of stay for acute myocardial infarction in
      China.
AB  - BACKGROUND: China is experiencing increasing burden of acute myocardial
      infarction (AMI) in the face of limited medical resources. Hospital length of
      stay (LOS) is an important indicator of resource utilization. METHODS: We used
      data from the Retrospective AMI Study within the China Patient-centered
      Evaluative Assessment of Cardiac Events, a nationally representative sample of
      patients hospitalized for AMI during 2001, 2006, and 2011. Hospital-level
      variation in risk-standardized LOS (RS-LOS) for AMI, accounting for differences
      in case mix and year, was examined with two-level generalized linear mixed
      models. A generalized estimating equation model was used to evaluate hospital
      characteristics associated with LOS. Absolute differences in RS-LOS and 95%
      confidence intervals were reported. RESULTS: The weighted median and mean LOS
      were 13 and 14.6 days, respectively, in 2001 (n = 1,901), 11 and 12.6 days in
      2006 (n = 3,553), and 11 and 11.9 days in 2011 (n = 7,252). There was substantial
      hospital level variation in RS-LOS across the 160 hospitals, ranging from 9.2 to
      18.1 days. Hospitals in the Central regions had on average 1.6 days (p = 0.02)
      shorter RS-LOS than those in the Eastern regions. All other hospital
      characteristics relating to capacity for AMI treatment were not associated with
      LOS. CONCLUSIONS: Despite a marked decline over the past decade, the mean LOS for
      AMI in China in 2011 remained long compared with international standards. Inter
      hospital variation is substantial even after adjusting for case mix. Further
      improvement of AMI care in Chinese hospitals is critical to further shorten LOS
      and reduce unnecessary hospital variation.

PMID- 25603875
TI  - Pain care for patients with epidermolysis bullosa: best care practice guidelines.
AB  - BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a group of rare
      disorders that have multi-system effects and patients present with a number of
      both acute and chronic pain care needs. Effects on quality of life are
      substantial. Pain and itching are burdensome daily problems. Experience with, and
      knowledge of, the best pain and itch care for these patients is minimal. Evidence
      based best care practice guidelines are needed to establish a base of knowledge
      and practice for practitioners of many disciplines to improve the quality of life
      for both adult and pediatric patients with EB. METHODS: The process was begun at
      the request of Dystrophic Epidermolysis Bullosa Research Association
      International (DEBRA International), an organization dedicated to improvement of
      care, research and dissemination of knowledge for EB patients worldwide. An
      international panel of experts in pain and palliative care who have extensive
      experience caring for patients with EB was assembled. Literature was reviewed and
      systematically evaluated. For areas of care without direct evidence, clinically
      relevant literature was assessed, and rounds of consensus building were
      conducted. The process involved a face-to-face consensus meeting that involved a
      family representative and methodologist, as well as the panel of clinical
      experts. During development, EB family input was obtained and the document was
      reviewed by a wide variety of experts representing several disciplines related to
      the care of patients with EB. RESULTS: The first evidence-based care guidelines
      for the care of pain in EB were produced. The guidelines are clinically relevant
      for care of patients of all subtypes and ages, and apply to practitioners of all
      disciplines involved in the care of patients with EB. When the evidence suggests
      that the diagnosis or treatment of painful conditions differs between adults and
      children, it will be so noted. CONCLUSIONS: Evidence-based care guidelines are a
      means of standardizing optimal care for EB patients, whose disease is often times
      horrific in its effects on quality of life, and whose care is resource-intensive
      and difficult. The guideline development process also highlighted areas for
      research in order to improve further the evidence base for future care.

PMID- 25603879
TI  - Surgery for anorectal strictures following stapled procedures.

PMID- 25603878
TI  - Prognostic factors and treatment outcomes in patients with Small Bowel
      Adenocarcinoma (SBA): the Royal Marsden Hospital (RMH) experience.
AB  - BACKGROUND: SBA is a rare tumour which carries a poor prognosis. Very few data on
      prognostic factors and treatment outcomes are available. We conducted a
      retrospective analysis of patients treated for SBA at our institution. METHODS:
      Clinico-pathological characteristics, treatments and outcomes of all the SBA
      patients treated consecutively from 1996 to 2011 were retrospectively collected.
      The prognostic value of baseline factors was assessed using the Cox regression
      model. The Kaplan-Meier method was used to estimate the survival outcomes.
      RESULTS: Eighty-four patients with SBA were treated during the study period. Of
      these, 48 presented with early stage SBA, while 36 had unresectable disease. All
      early stage SBA patients (58.3% males; median age, 59 years) underwent resection
      (R0 in 44/48) and 27 (56%) received adjuvant chemotherapy. Median relapse-free
      survival and overall survival (OS) were 31.1 months (95% CI: 8.0-54.3) and 42.9
      (95% CI: 0-94.9), respectively. In univariate analyses, poor histological
      differentiation (p = 0.025) and lymphovascular invasion (p = 0.003) were
      prognostic for OS. In the group of patients with relapsed, unresectable or
      metastatic disease (n = 59), systemic chemotherapy was administered in 46 cases
      (78%). The response rate to first line chemotherapy was 50%. Median progression
      free survival and OS were 8.8 (95% CI: 5.5-12.3) and 12.8 months (95% CI: 8.4
      17.2), respectively. In univariate analyses, low albumin (p = 0.041) and high
      platelet count (p = 0.007) were prognostic for OS. CONCLUSION: Prospective
      clinical trials are needed to inform the management of SBA patients. Prognostic
      factors evaluated in our series may be useful for patient stratification and
      treatment selection in future studies.

PMID- 25603880
TI  - Beyond landraces: developing improved germplasm resources for underutilized
      species - a case for Bambara groundnut.
AB  - The potential for underutilized crops (also known as minor, neglected or orphan
      crops) to improve food and nutrition security has been gaining prominence within
      the research community in recent years. This is due to their significance for
      diversified agricultural systems which is a necessary component of future
      agriculture to address food and nutritional security concerns posed by changing
      climate and a growing world population. Developing workable value chain systems
      for underutilized crop species, coupled with comparative trait studies with major
      crops, potentially allows us to identify suitable agricultural modalities for
      such species. Bambara groundnut (Vigna subterranea L. Verdc.), an underutilized
      leguminous species, is of interest for its reported high levels of drought
      tolerance in particular, which contributes to environmental resilience in semi
      arid environments. Here, we present a synopsis of suitable strategies for the
      genetic improvement of Bambara groundnut as a guide to other underutilized crop
      species. Underutilized crops have often been adapted over thousands of years in
      particular regions by farmers and largely still exist as landraces with little or
      no genetic knowledge of key phenotypic traits. Breeding in these species is
      fundamentally different to breeding in major crops, where significant pedigree
      structures and history allow highly directed improvement. In this regard,
      deploying new integrated germplasm development approaches for variety development
      and genetic analysis, such as multi-parent advance generation inter-crosses
      (MAGIC), within breeding programmes of underutilized species will be important to
      be able to fully utilize such crops. 

PMID- 25603881
TI  - Advances in the measurement and computation of thermal phonon transport
      properties.
AB  - Heat conduction by phonons is a ubiquitous process that incorporates a wide range
      of physics and plays an essential role in applications ranging from space power
      generation to LED lighting. Heat conduction has been studied for over two hundred
      years, yet many of the microscopic details have remained unknown in most
      crystalline solids, including which phonon-phonon interactions are primarily
      responsible for thermal resistance and how heat is distributed among the broad
      thermal spectrum. This lack of knowledge was the result of limitations on the
      available tools to study heat conduction. However, recent advances in both
      computation and experiment are enabling an unprecedented microscopic view of
      thermal transport by phonons in both bulk and nanostructured crystals, from the
      level of atomic bonding to mesoscopic transport in complex devices. In this
      topical review, we examine these techniques and the microscopic insights gained
      into the science and engineering of heat conduction. 

PMID- 25603883
TI  - Estimation of changes in maternal mortality in a rural district of northern
      Tanzania during the last 50 years.
AB  - OBJECTIVE: Maternal mortality remains a major challenge worldwide. Reliable
      information concerning ratios and trends is essential for resource mobilization
      and assessment of progress towards the Millennium Development Goals. DESIGN:
      Assessment of levels and trends in maternal mortality during the last 50 years.
      SETTING: Sengerema district, rural North Tanzania. POPULATION: Number of
      deliveries, births, admissions, maternal deaths and causes of maternal mortality
      in the only hospital in the area. METHODS: We compiled a database from the annual
      hospital reports for the period of 1962-2011 to obtain estimated maternal
      mortality ratio for each decade. MAIN OUTCOME MEASURES: Maternal mortality ratio
      for each decade and classification of maternal deaths. RESULTS: Of 629 maternal
      deaths, 490 (77.9%) could be classified as either direct or indirect and causes
      of mortality ascertained. Of the 361 direct causes (73.7%), hemorrhage (29.8%)
      and sepsis (20.4%) were the leading causes. Of the 129 indirect causes (26.3%),
      anemia during pregnancy (6.5%), meningitis (4.1%), HIV-AIDS (3.5%), malaria
      (2.9%), heart diseases (2.4%) and relapsing fever (2.0%) were most often
      diagnosed. Since 1962, a 63% decrease in maternal mortality ratio has been
      achieved. The hospital-based maternal mortality ratio decreased from 770/100,000
      to 282/100,000 in the last decade (95% confidence interval 244/100,000,
      320/100,000). The yearly decline since 1962 was 1.3%. CONCLUSIONS: During the
      last 50 years we have witnessed a reduction of maternal mortality and
      improvements in maternal health. Progress has been made towards improving
      Millennium Development Goal 5, although only a prospective population-based
      survey will provide the ultimate answer.

PMID- 25603882
TI  - The use of mediation analysis to assess the effects of a behaviour change
      communication strategy on bed net ideation and household universal coverage in
      Tanzania.
AB  - BACKGROUND: SBCC campaigns are designed to act on cognitive, social and emotional
      factors at the individual or community level. The combination of these factors,
      referred to as 'ideation', play a role in determining behaviour by reinforcing
      and confirming decisions about a particular health topic. This study introduces
      ideation theory and mediation analysis as a way to evaluate the impact of a
      malaria SBCC campaign in Tanzania, to determine whether exposure to a
      communication programme influenced universal coverage through mediating
      ideational variables. METHODS: A household survey in three districts where
      community change agents (CCAs) were active was conducted to collect information
      on ITN use, number of ITNs in the household, and perceptions about ITN use and
      ownership. Variables relating to attitudes and beliefs were combined to make 'net
      ideation'. Using an ideational framework, a mediation analysis was conducted to
      see the impact exposure to a CCA only, mass media and community (M & C) messaging
      only, or exposure to both, had on household universal coverage, through the
      mediating variable net ideation. RESULTS: All three levels of exposure (CCA, M &
      C messaging, or exposure to both) were significantly associated with increased
      net ideation (CCA: 0.283, 95% CI: 0.136-0.429, p-value: <0.001; M & C: 0.128, 95%
      CI: 0.032-0.334, p-value: 0.018; both: 0.376, 95% CI: 0.170-0.580, p-value:
      <0.001). Net ideation also significantly increased the odds of having universal
      coverage (CCAOR: 1.265, 95% CI: 1.118-1.433, p-value: <0.001; M & COR: 1.264, 95%
      CI: 1.117-1.432, p-value: <0.001, bothOR: 1.260, 95% CI: 1.114-1.428, p-value:
      <0.001). There were no significant direct effects between any exposure and
      universal coverage when controlling for net ideation. CONCLUSIONS: The results of
      this study indicate that mediation analysis is an applicable new tool to assess
      SBCC campaigns. Ideation as a mediator of the effects of communication exposure
      on household universal coverage has implications for designing SBCC to support
      both mass and continuous distribution efforts, since both heavily rely on
      consumer participation to obtain and maintain ITNs. Such systems can be
      strengthened by SBCC programming, generating demand through improving social
      norms about net ownership and use, perceived benefits of nets, and other
      behavioural constructs.

PMID- 25603884
TI  - New GH16 beta-glucanase from Paenibacillus barcinonensis BP-23 releases a complex
      pattern of mixed-linkage oligomers from barley glucan.
AB  - The gene coding for a lichenase from Paenibacillus barcinonensis BP-23, a
      powerful carbohydrate-degrading strain, was obtained using a genome walking
      strategy and expressed in Escherichia coli for further characterization. The
      amino acid sequence deduced from lic16A revealed that the lichenase is a single
      domain enzyme belonging to the GH16 family. Purified recombinant Lic16A showed
      exclusive activity on beta-1,3-1,4-glucans, showing a Km of 16.88 mg/mL and a
      Vmax of 266.09 U/mg using lichenan as a substrate. Lic16A was stable at 55 
      degrees C for at least 3 H in moderate pH conditions. Thin-layer chromatography
      analysis showed that the enzyme released a complex mixture of hydrolysis
      products, which consisted of different length oligosaccharides of intermediate
      mobility among cellooligomers. The health benefits of beta-glucans's consumption
      and the increased interest for the use of their oligomers as prebiotics add
      interest to the study of Lic16A for the production of beta-glucan-derived
      oligosaccharides and the evaluation of their biotechnological potential. This is
      the first report on beta-1,3-1,4-glucanase produced by P. barcinonensis. 

PMID- 25603885
TI  - Pd-catalyzed alpha-selective C(sp3)-H acetoxylation of amides through an unusual
      cyclopalladation mechanism.
AB  - We report the first example of Pd-catalyzed site-selective alpha-C(sp(3))-H
      oxidation/acetoxylation of amides through an unusual [4,6]-bicyclic metallacycle
      intermediate with 1-aminoanthraquinone as a new bidentate directing group. In
      addition to the distinct mechanism and high efficiency, the reaction is highly
      appealing due to the ample commercial source, low-cost, as well as easy removal
      and recycling of the auxiliary group. 

PMID- 25603886
TI  - Bullous lesions on the extremities of an incarcerated man.

PMID- 25603887
TI  - Structural investigation of resorcinol based symmetrical banana mesogens by XRD,
      NMR and polarization measurements.
AB  - Synthesis and structural characterization of two novel symmetrical banana
      mesogens built from resorcinol with seven phenyl rings linked by ester and imine
      with a terminal dodecyl/dodecyloxy chain has been carried out. Density functional
      theory (DFT) has been employed for obtaining the geometry optimized structures,
      the dipole moments and (13)C NMR chemical shifts. The HOPM and DSC studies
      revealed enantiotropic B2 and B7 phases for the dodecyl and dodecyloxy homologs
      respectively. The powder X-ray studies of both the mesogens indicate the presence
      of layer ordering. The polarization measurements reveal an anti-ferroelectric
      switching for the B2 phase of the dodecyl homolog whose structure has been
      identified as SmCSPA. The B7 phase of the dodecyloxy homolog was found to be non
      switchable. High resolution (13)C NMR study of the dodecyl homolog in its
      mesophase has been carried out. (13)C-(1)H dipolar couplings obtained from the 2
      dimensional separated local field spectroscopy experiment were used to obtain the
      orientational order parameters of the different segments of the mesogen. Very
      large (13)C-(1)H dipolar couplings observed for the carbons of the central phenyl
      ring (9.7-12.3 kHz) in comparison to the dipolar couplings of those of the side
      arm phenyl rings (less than 3 kHz) are a direct consequence of the ordering in
      the banana phase and the shape of the molecule. From the ratio of the local order
      parameter values, the bent-angle of the mesogen could be determined in a straight
      forward manner to be 120.5 degrees . 

PMID- 25603888
TI  - Nanostructure controlled sustained delivery of human growth hormone using
      injectable, biodegradable, pH/temperature responsive nanobiohybrid hydrogel.
AB  - The clinical efficacy of a therapeutic protein, the human growth hormone (hGH),
      is limited by its short plasma half-life and premature degradation. To overcome
      this limitation, we proposed a new protein delivery system by the self-assembly
      and intercalation of a negatively charged hGH onto a positively charged 2D
      layered double hydroxide nanoparticle (LDH). The LDH-hGH ionic complex, with an
      average particle size of approximately 100 nm, retards hGH diffusion.
      Nanobiohybrid hydrogels (PAEU/LDH-hGH) were prepared by dispersing the LDH-hGH
      complex into a cationic pH- and temperature-sensitive injectable PAEU copolymer
      hydrogel to enhance sustained hGH release by dual ionic interactions.
      Biodegradable copolymer hydrogels comprising poly(beta-amino ester urethane) and
      triblock poly(epsilon-caprolactone-lactide)-poly(ethylene glycol)-poly-(epsilon
      caprolactone-lactide) (PCLA-PEG-PCLA) were synthesized and characterized. hGH was
      self-assembled and intercalated onto layered LDH nanoparticles through an anion
      exchange technique. X-ray diffraction and zeta potential results showed that the
      LDH-hGH complex was prepared successfully and that the PAEU/LDH-hGH nanobiohybrid
      hydrogel had a disordered intercalated nanostructure. The biocompatibility of the
      nanobiohybrid hydrogel was confirmed by an in vitro cytotoxicity test. The in
      vivo degradation of pure PAEU and its nanobiohybrid hydrogels was investigated
      and it showed a controlled degradation of the PAEU/LDH nanobiohybrids compared
      with the pristine PAEU copolymer hydrogel. The LDH-hGH loaded injectable
      hydrogels suppressed the initial burst release of hGH and extended the release
      period for 13 days in vitro and 5 days in vivo. The developed nanohybrid hydrogel
      has the potential for application as a protein carrier to improve patient
      compliance. 

PMID- 25603890
TI  - A double-blind randomized study comparing the association of Retinol and LR2412
      with tretinoin 0.025% in photoaged skin.
AB  - INTRODUCTION: Topical tretinoin is considered the gold standard to treat
      photoaged skin, but it is associated with side effects and only available upon
      prescription. AIM OF THE STUDY: To compare the efficacy, tolerance, and
      perception of a fixed proprietary combination (Retinol 0.2%/LR2412 2%) vs.
      tretinoin 0.025% cream in women with photoaged skin. MATERIAL/METHODS: In this
      randomized, parallel, double-blind, controlled clinical study, women applied to
      the entire face for 3 months in the morning a SPF 50 sunscreen and in the evening
      either the association of Retinol 0.2%/LR2412 2% or tretinoin 0.025%. Clinical
      and instrumental parameters were assessed at days 0, 28, 56, and 84. Subject
      perception of the efficacy, tolerance and cosmeticity of the tested products were
      assessed at days 28, 56, and 84. RESULTS: A total of 120 women (60 to Retinol
      0.2%/LR2412 2% cream and 60 to tretinoin 0.025% cream) were included in the
      study. Both products improved considerably wrinkles, mottled pigmentation, pores,
      and global photodamage. No statistically significant differences were noted
      between Retinol 0.2%/LR2412 2% cream and tretinoin 0.025% cream. Adverse effects
      were mostly graded mild. Overall, Retinol 0.2%/LR2412 2% cream was better
      tolerated than tretinoin 0.025% cream. At all visits, subject perception of the
      association of Retinol 0.2%/LR2412 2% was either comparable to or better than
      tretinoin 0.025% cream. CONCLUSION: The treatment outcome of Retinol 0.2%/LR2412
      2% cream does not differ from the one of tretinoin 0.025% cream. Clinical results
      were not statistically different. Furthermore, Retinol 0.2%/LR2412 2% cream is
      better tolerated and better perceived by women used to rejuvenation procedures.

PMID- 25603893
TI  - Magnetoencephalographic evidence of early right hemisphere overactivation during
      metaphor comprehension in schizophrenia.
AB  - Whereas language processing in neurotypical brains is left lateralized,
      individuals with schizophrenia (SZ) display a bilateral or reversed pattern of
      lateralization. We used MEG to investigate the implications of this atypicality
      on fine (left hemisphere) versus coarse (right hemisphere) semantic processing.
      Ten SZ and 14 controls were presented with fine (conventional metaphor, literal,
      and unrelated expressions) and coarse (novel metaphor) linguistic stimuli.
      Results showed greater activation of the right hemisphere for novel metaphors and
      greater bilateral activation for unrelated expressions at the M170 window in SZ.
      Moreover, at the M350, SZ showed reduced bilateral activation. We conclude that
      SZ are overreliant on early-stage coarse semantic processing. As a result, they
      jump too quickly to remote conclusions, with limited control over the meanings
      they form. This may explain one of the core symptoms of the disorder-loose
      associations. 

PMID- 25603892
TI  - Genome-wide transcriptomic and phylogenetic analyses reveal distinct aluminum
      tolerance mechanisms in the aluminum-accumulating species buckwheat (Fagopyrum
      tataricum).
AB  - BACKGROUND: Similar to common buckwheat (Fagopyrum esculentum), tartary buckwheat
      (Fagopyrum tataricum) shows a high level of aluminum (Al) tolerance and
      accumulation. However, the molecular mechanisms for Al detoxification and
      accumulation are still poorly understood. To begin to elucidate the molecular
      basis of Al tolerance and accumulation, we used the Illumina high-throughput mRNA
      sequencing (RNA-seq) technology to conduct a genome-wide transcriptome analysis
      on both tip and basal segments of the roots exposed to Al. RESULTS: By using the
      Trinity method for the de novo assembly and cap3 software to reduce the
      redundancy and chimeras of the transcripts, we constructed 39,815 transcripts
      with an average length of 1184 bp, among which 20,605 transcripts were annotated
      by BLAST searches in the NCBI non-redundant protein database. Gene Ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed
      that expression of genes involved in the defense of cell wall toxicity and
      oxidative stress was preferentially induced by Al stress. Our RNA-seq data also
      revealed that organic acid metabolism was unlikely to be a rate-limiting step for
      the Al-induced secretion of organic acids in buckwheat. We identified two citrate
      transporter genes that were highly induced by Al and potentially involved in the
      release of citrate into the xylem. In addition, three of four conserved Al
      tolerance genes were found to be duplicated in tartary buckwheat and display
      diverse expression patterns. CONCLUSIONS: Nearly 40,000 high quality transcript
      contigs were de novo assembled for tartary buckwheat, providing a reference
      platform for future research work in this plant species. Our differential
      expression and phylogenetic analysis revealed novel aspects of Al-tolerant
      mechanisms in buckwheat.

PMID- 25603894
TI  - Integrated genome sequence and linkage map of physic nut (Jatropha curcas L.), a
      biodiesel plant.
AB  - The family Euphorbiaceae includes some of the most efficient biomass
      accumulators. Whole genome sequencing and the development of genetic maps of
      these species are important components in molecular breeding and genetic
      improvement. Here we report the draft genome of physic nut (Jatropha curcas L.),
      a biodiesel plant. The assembled genome has a total length of 320.5 Mbp and
      contains 27,172 putative protein-coding genes. We established a linkage map
      containing 1208 markers and anchored the genome assembly (81.7%) to this map to
      produce 11 pseudochromosomes. After gene family clustering, 15,268 families were
      identified, of which 13,887 existed in the castor bean genome. Analysis of the
      genome highlighted specific expansion and contraction of a number of gene
      families during the evolution of this species, including the ribosome
      inactivating proteins and oil biosynthesis pathway enzymes. The genomic sequence
      and linkage map provide a valuable resource not only for fundamental and applied
      research on physic nut but also for evolutionary and comparative genomics
      analysis, particularly in the Euphorbiaceae.

PMID- 25603895
TI  - Correlation between genetic diversity and environmental suitability: taking
      uncertainty from ecological niche models into account.
AB  - The hindcast of shifts in the geographical ranges of species as estimated by
      ecological niche modelling (ENM) has been coupled with phylogeographical
      patterns, allowing the inference of past processes that drove population
      differentiation and genetic variability. However, more recently, some studies
      have suggested that maps of environmental suitability estimated by ENM may be
      correlated to species' abundance, raising the possibility of using environmental
      suitability to infer processes related to population demographic dynamics and
      genetic variability. In both cases, one of the main problems is that there is a
      wide variation in ENM development methods and climatic models. In this study, we
      analyse the relationship between heterozygosity (He) and environmental
      suitability from multiple ENMs for 25 population estimates for Dipteryx alata, a
      widely distributed, endemic tree species of the Cerrado region of central Brazil.
      We propose a new approach for generating a statistical distribution of
      correlations under randomly generated ENM. The confidence intervals from these
      distributions indicate how model selection with different properties affects the
      ability to detect a correlation of interest (e.g. the correlation between He and
      suitability). Additionally, our approach allows us to explore which particular
      ensemble of ENMs produces the better result for finding an association between
      environmental suitability and He. Caution is necessary when choosing a method or
      a climatic data set for modelling geographical distributions, but the new
      approach proposed here provides a conservative way to evaluate the ability of
      ensembles to detect patterns of interest. 

PMID- 25603896
TI  - Effect of ohmic heating of soymilk on urease inactivation and kinetic analysis in
      holding time.
AB  - To verify the effect of the ohmic heating on the urease activity in the soymilk,
      the ohmic heating methods with the different electrical field conditions (the
      frequency and the voltage ranging from 50 to 10 kHz and from 160 to 220 V,
      respectively) were employed. The results showed that if the value of the urease
      activity measured with the quantitative spectrophotometry method was lower than
      16.8 IU, the urease activity measured with the qualitative method was negative.
      The urease activity of the sample ohmically heated was significantly lower than
      that of the sample conventionally heated (P < 0.01) at the same target
      temperature. It was concluded that the electrical field enhanced the urease
      inactivation. In addition, the inactivation kinetics of the urease in the soymilk
      could be described with a biphasic model during holding time at a target
      temperature. Thus, it was concluded that the urease in the soymilk would contain
      2 isoenzymes, one is the thermolabile fraction, the other the thermostable
      fraction, and that the thermostable isoenzyme could not be completely inactivated
      when the holding time increased, whether the soymilk was cooked with the
      conventional method or with the ohmic heating method. Therefore, the electric
      field had no effect on the inactivation of the thermostable isoenzyme of the
      urease. 

PMID- 25603897
TI  - Blood flow restricted and traditional resistance training performed to fatigue
      produce equal muscle hypertrophy.
AB  - This study investigated the hypertrophic potential of load-matched blood-flow
      restricted resistance training (BFR) vs free-flow traditional resistance training
      (low-load TRT) performed to fatigue. Ten healthy young subjects performed
      unilateral BFR and contralateral low-load TRT elbow flexor dumbbell curl with 40%
      of one repetition maximum until volitional concentric failure 3 days per week for
      6 weeks. Prior to and at 3 (post-3) and 10 (post-10) days post-training, magnetic
      resonance imaging (MRI) was used to estimate elbow flexor muscle volume and
      muscle water content accumulation through training. Acute changes in muscle
      thickness following an early vs a late exercise bout were measured with
      ultrasound to determine muscle swelling during the immediate 0-48 h post
      exercise. Total work was threefold lower for BFR compared with low-load TRT (P <
      0.001). Both BRF and low-load TRT increased muscle volume by approximately 12% at
      post-3 and post-10 (P < 0.01) with no changes in MRI-determined water content.
      Training increased muscle thickness during the immediate 48 h post-exercise (P <
      0.001) and to greater extent with BRF (P < 0.05) in the early training phase. In
      conclusion, BFR and low-load TRT, when performed to fatigue, produce equal muscle
      hypertrophy, which may partly rely on transient exercise-induced increases in
      muscle water content.

PMID- 25603899
TI  - Common single nucleotide variants underlying drug addiction: more than a decade
      of research.
AB  - Drug-related phenotypes are common complex and highly heritable traits. In the
      last few years, candidate gene (CGAS) and genome-wide association studies (GWAS)
      have identified a huge number of single nucleotide polymorphisms (SNPs)
      associated with drug use, abuse or dependence, mainly related to alcohol or
      nicotine. Nevertheless, few of these associations have been replicated in
      independent studies. The aim of this study was to provide a review of the SNPs
      that have been most significantly associated with alcohol-, nicotine-, cannabis-
      and cocaine-related phenotypes in humans between the years of 2000 and 2012. To
      this end, we selected CGAS, GWAS, family-based association and case-only studies
      published in peer-reviewed international scientific journals (using the
      PubMed/MEDLINE and Addiction GWAS Resource databases) in which a significant
      association was reported. A total of 371 studies fit the search criteria. We then
      filtered SNPs with at least one replication study and performed meta-analysis of
      the significance of the associations. SNPs in the alcohol metabolizing genes, in
      the cholinergic gene cluster CHRNA5-CHRNA3-CHRNB4, and in the DRD2 and ANNK1
      genes, are, to date, the most replicated and significant gene variants associated
      with alcohol- and nicotine-related phenotypes. In the case of cannabis and
      cocaine, a far fewer number of studies and replications have been reported,
      indicating either a need for further investigation or that the genetics of
      cannabis/cocaine addiction are more elusive. This review brings a global state-of
      the-art vision of the behavioral genetics of addiction and collaborates on
      formulation of new hypothesis to guide future work. 

PMID- 25603898
TI  - High interindividual variability in the CD4/CD8 T cell ratio and natalizumab
      concentration levels in the cerebrospinal fluid of patients with multiple
      sclerosis.
AB  - Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the
      cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS)
      patients may have implications on central nervous (CNS) immune surveillance. With
      regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at
      delineating a relationship between free NZB, cell-bound NZB, adhesion molecule
      (AM) expression and the treatment-associated shift in the CSF T cell ratio.
      Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T
      cells from 10 patients with non-inflammatory neurological diseases and five newly
      diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1),
      leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB
      saturation levels, and T cell ratios were analysed by flow cytometry. NZB
      concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower
      NZB saturation levels (P<0.02) and a higher surface expression of ICAM-1 and LFA
      1 (P<0.001) were observed on CSF CD8 T cells. CSF T cell ratios (0.3-2.1) and NZB
      concentrations (0.01-0.42 ug/ml) showed a pronounced interindividual variance. A
      correlation between free NZB, cell-bound NZB or AM expression levels and the CSF
      T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF
      T cell ratio were observed in one case. The differential NZB saturation and AM
      expression of CSF CD8 T cells may contribute to their relative enrichment in the
      CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels,
      as normalization occurred quickly. The latter may be important concerning a fast
      reconstitution of CNS immune surveillance.

PMID- 25603900
TI  - Changes in emotional distress, short term memory, and sustained attention
      following 6 and 12 sessions of progressive muscle relaxation training in 10-11
      years old primary school children.
AB  - PURPOSE: This study compared the effects of 6 and 12 sessions of relaxation
      training on emotional distress, short-term memory, and sustained attention in
      primary school children. METHODS: Participants (N = 132) aged 10 and 11 years old
      participated in this study. All participants and their parents provided written
      informed consent. Participants completed the measurement instruments before and
      after the completion of relaxation training. RESULTS: Nearly half (49%) of all
      respondents reported moderate to extremely severe stress, and 80 and 61% reported
      moderate to extremely severe anxiety and depression, respectively. The results of
      a one-way analysis of variance revealed a significant difference among the groups
      in mean changes in short-term memory. A greater memory increase was observed in
      the 12-session than in the six-session and no-training group. CONCLUSION: It can
      be conceived that 12-session of training should be considered when prescribing
      relaxation regimens as a nonspecific clinical treatment (i.e. for healthy
      students).

PMID- 25603902
TI  - [Guideline on diagnosis and treatment of abnormal uterine bleeding].

PMID- 25603901
TI  - Molecular and clinical analysis of TRPC6 and AGTR1 genes in patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and progressive
      vascular disorder characterized by increased pulmonary vascular resistance and
      right heart failure. The aim of this study was to analyze 5'UTR region in
      canonical transient receptor potential isoform 6 (TRPC6) and 3'UTR region in
      Angiotensin II type I receptor (AGTR1) genes in patients with idiopathic and
      associated PAH. Correlation among mutations and clinical and functional
      parameters was further analyzed. METHODS: Analysis of TRPC6 and AGTR1 genes was
      performed by polymerase chain reaction (PCR) and direct sequencing. We used a non
      parametric test to determine if significant differences were found between the
      groups studied and chi-square test to compare clinical and hemodynamic variables
      among genotypes. RESULTS: Fifty five patients and fifty two controls were
      included in this study. We found statistically significant differences for c.1
      361A > T (p = 0.0077), c.1-254C > G (p < 0.0001) and c.1-218C > T (p = 0.0021) in
      TRPC6 gene and c.1166A > C (p < 0.001) in AGTR1 gene, between patients and
      controls. Idiopathic PAH patients (IPAH) and controls presented significant
      differences for all 3 TRPC6 polymorphisms (p = 0.020), (p = 0.002) and (p =
      0.008) respectively, and also showed differences for AGTR1 gene (p < 0.001). In
      associated PAH (APAH) patients we found statistical differences for c.1-254C > G
      (p < 0.001) and c.1-218C > T (p = 0.001) in TRPC6 gene and c.1166A > C (p =
      0.001) in AGTR1 gene. Several clinical and hemodynamic parameters showed
      significant differences between carriers and non-carriers of these single
      nucleotide polymorphisms (SNPs). Nineteen patients were carriers of all 3 SNPs in
      TRPC6 gene and presented a more severe phenotype with differences in mean
      pulmonary arterial pressure (p = 0.016), systolic pulmonary arterial pressure (p
      = 0.040), cardiac index (p < 0.001) and 6 minute walking test (p = 0.049). 16 of
      these patients harbored the SNP in AGTR1 gene. These patients showed differences
      in age at diagnosis (p = 0.049), mean pulmonary arterial pressure (p = 0.033),
      cardiac index (p = 0.002) and 6 minute walking test (p = 0.039). CONCLUSIONS: PAH
      is a rare disease with pulmonary vascular remodeling caused in part by a
      heterogeneous constellation of genetic arrangements. This study seems to suggest
      that c.1-361A > T, c.1-254C > G and c.1-218C > T polymorphisms in TRPC6 gene and
      c.1166A > C polymorphism in AGTR1 could have a role in the development of this
      disease.

PMID- 25603903
TI  - [The importance of the pregnancy with thyroid disease].

PMID- 25603904
TI  - [Correlation between thyroid hormones and renal function in severe pre-eclampsia
      patients with hypothyroidism].
AB  - OBJECTIVE: To study effects of different degree of hypothyroidism in severe pre
      eclampsia (S-PE) pregnant women on renal function and the correlation between
      them. METHODS: 46 S-PE patients with subclinical hypothyroidism (SCH) registered
      for treatment in the Shengjing Hospital of China Medical University from May 2011
      to March 2013 were selected into SCH group, and 23 S- PE with overt
      hypothyroidism (OH) were selected into OH group, and 109 S- PE with normal
      thyroid stimulating hormone (TSH) levels were selected into simple group. Thyroid
      hormone and kidney function tests were analyzed in pregnant women with S-PE. We
      made an analysis of the relative risk of the detection rate of abnormal renal
      function and also the relationship between the levels of thyroid hormone and
      serum uric acid, serum urea and creatinine in patients with S- PE. RESULTS: (1)
      In SCH group serum TSH was (6.1+/-3.2) mU/L, free triiodothyronine (FT3) was
      (4.0+/-0.6) pmol/L, free thyroxine(FT4)was (11.8+/-1.5) pmol/L; in OH group serum
      TSH was (5.2+/-1.3) mU/L, FT3 was (3.7+/-0.6) pmol/L, FT4 was (9.3+/-0.5) pmol/L;
      in simple S-PE group serum TSH was (1.9+/-0.8) mU/L, FT3 was (4.0+/-0.8) pmol/L
      and FT4 was (11.9+/-1.9) pmol/L. TSH in SCH group was significantly higher than
      that in simple S-PE group (P>0.01), the difference of in SCH and OH group were
      not statistically significant (P>0.05). The difference of FT3 in three groups
      were not statistically significant (P < 0.05); FT4 in OH group was significantly
      lower than thoes in SCH and simple groups (P < 0.05). (2) Serum uric acid,
      creatinine and urea levels in OH group was(436+/-114),(75+/-15)umol/L and (6+/
      3)mmol/L, in simple S-PE group they were(378+/-114), (65+/-22) umol/L and (5+/
      3)mmol/L. In comparison, the differences was statistically significant(P < 0.05).
      The differences were not statistically significant in SCH and OH groups (P >
      0.05).(3)The abnormal detection rate of uric acid was significantly higher in SCH
      than that in OH group [46% (21/46) versus 22% (5/23), OR = 3.0, P < 0.05]. The
      comparison of remaining index has no statistical significance(P > 0.05).(4)In SCH
      group there was a significant inverse correlation of serum FT3 with serum urea
      levels, serum creatinine and serum uric acid (r = -0.32, -0.58, -0.35, P < 0.05).
      There was not a correlation of serum TSH, FT4 with indicators of renal function
      (P > 0.05). In OH group there was a negative correlation between FT3 and serum
      creatinine concentrations (r = -0.40, P < 0.05). In OH group there was not a
      correlation of FT3 with serum uric acid and urea(P > 0.05). There was a positive
      correlation between TSH and serum creatinine in simple S-PE group (r = 0.20, P =
      0.04). There was not a correlation between TSH and serum urea(r = 0.04, P =
      0.65), and serum uric acid (r = 0.12, P = 0.20). CONCLUSIONS: There was effect of
      different hypothyrosis state in pre-eclampsia patients on renal function. Serum
      uric acid, urea and creatinine concentrations in S-PE pregnant women with OH were
      significantly higher than those in simple S-PE group with normal TSH. There was a
      negative correlation between FT3 and serum creatinine in S- PE. Hence the thyroid
      function should be regularly monitored in S- PE patients to find damage of renal
      function and management hypothyrosis.

PMID- 25603905
TI  - [Clinical or subclinical hypothyroidism and thyroid autoantibody before 20 weeks
      pregnancy and risk of preterm birth: a systematic review].
AB  - OBJECTIVE: To evaluate the relationship between clinical or subclinical
      hypothyroidism and positive thyroid autoantibody before 20 weeks pregnancy and
      risk of preterm birth. METHODS: Literature search was done in PubMed, EMBASE,
      Wanfang Medical Database, China Academic Journal Network Publishing Database and
      China Biology Medicine disc databases from January 1st, 1980 to December 31th,
      2013. The following search terms were used:hypothyroidism, subclinical
      hypothyroidism, hypothyroxinnism, thyroid antibody, preterm labor, preterm birth,
      etc. (1) Criteria for inclusion:cohort studies and clinical studies were
      included; only articles that described at least 10 patients were eligible;the
      exposure was clinical or subclinical hypothyroidism and positive thyroid
      autoantihody, and outcome was preterm birth. (2) The excluded subjects were
      articles that described less than 10 patients; controls were pregnant women
      without eurothyrodisim. Meta-analysis was performed by RevMan 5. The relationship
      between clinical or subclinical hypothyroidism and positive thyroid autoantibody
      and risk of preterm birth was evaluated by OR or RR. RESULTS: (1) Twenty cohort
      studies were enrolled. A total of 39 596 cases of preterm birth occurred among
      498 418 pregnant women. The controls in these studies were pregnant women with
      eurothyrodisim. (2) Clinical hypothyroidism in pregnancy: eight studies were
      included, reported data on 478 418 pregnant women (5 473 women with clinical
      hypothyroidism and 472 945 euthyroid pregnant women). The risk of preterm birth
      in pregnant women with clinical hypothyroidism was higher than those eurothyroid
      pregnant women in control group (OR = 1.25, 95% CI:1.15-1.36, P < 0.01). (3)
      Subclinical hypothyroidism in pregnancy: ten studies were included, reported data
      on 277 531 pregnant women (5 257 women with subclinical hypothyroidism and 272
      274 euthyroid pregnant women). The risk of preterm birth in pregnant women with
      subclinical hypothyroidism was higher than those in control group by random
      effects analysis (OR = 1.25, 95% CI:1.14-1.36, P < 0.01). (4) Thyroid
      autoantibodys positive in pregnancy:eleven studies were included, reported data
      on 28 781 pregnant women (3 036 women with thyroid autoanti body positive and 25
      745 euthyroid pregnant women). The risk of preterm birth in pregnant women with
      positive thyroid autoantibody was higher than those negative thyroid autoantibody
      in control group (OR = 1.47, 95% CI: 1.27- 1.70, P < 0.01). The funnel plots
      presented symmetrical graphics, indicating that there was no publication bias.
      CONCLUSION: Clinical or subclinical hypothyroidism and positive thyroid
      autoantibody in pregnant women is risk factors of preterm birth.

PMID- 25603906
TI  - [Comparison of the effect of different diagnostic criteria of subclinical
      hypothyroidism and positive TPO-Ab on pregnancy outcomes].
AB  - OBJECTIVE: To explore the effect of different diagnositic criteria of subclinical
      hypothyroidism using thyroid stimulating hormone (TSH) and positive thyroid
      peroxidase antibodies (TPO-Ab) on the pregnancy outcomes. METHODS: 3 244 pregnant
      women who had their antenatal care and delivered in Child and Maternity Health
      Hospital of Shannxi Province August from 2011 to February 2013 were recruited
      prospectively. According to the standard of American Thyroid Association (ATA),
      pregnant women with normal serum free thyroxine (FT4) whose serum TSH level> 2.50
      mU/L were diagnosed as subclinical hypothyroidism in pregnancy (foreign standard
      group). According to the Guideline of Diagnosis and Therapy of Prenatal and
      Postpartum Thyroid Disease made by Chinese Society of Endocrinology and Chinese
      Society of Perinatal Medicine in 2012, pregnant women with serum TSH level> 5.76
      mU/L, and normal FT4 were diagnosed as subclinical hypothyroidism in
      pregnancy(national standard group). Pregnant women with subclinical
      hypothyroidism whose serum TSH levels were between 2.50-5.76 mU/L were referred
      as the study observed group; and pregnant women with serum TSH level< 2.50 mU/L
      and negative TPO- Ab were referred as the control group. Positive TPO-Ab results
      and the pregnancy outcomes were analyzed. RESULTS: (1) There were 635 cases in
      the foreign standard group, with the incidence of 19.57% (635/3 244). And there
      were 70 cases in the national standard group, with the incidence of 2.16% (70/3
      244). There were statistically significant difference between the two groups (P <
      0.01). There were 565 cases in the study observed group, with the incidence of
      17.42% (565/3 244). There was statistically significant difference (P < 0.01)
      when compared with the national standard group; while there was no statistically
      significant difference (P > 0.05) when compared with the foreign standard group.
      (2) Among the 3 244 cases, 402 cases had positive TPO-Ab. 318 positive cases were
      in the foreign standard group, and the incidence of subclinical hypothyroidism
      was 79.10% (318/402). There were 317 negative cases in the foreign standard
      group, with the incidence of 11.15% (317/2 842). The difference was statistically
      significant (P < 0.01) between them. In the national standard group, 46 cases had
      positive TPO-Ab, with the incidence of 11.44% (46/402), and 24 cases had negative
      result, with the incidence of 0.84% (24/2 842). There were statistically
      significant difference (P < 0.01) between them. In the study observed group, 272
      cases were TPO-Ab positive, with the incidence of 67.66% (272/402), and 293 cases
      were negative, with the incidence of 10.31% (293/2 842), the difference was
      statistically significant (P < 0.01). (3) The incidence of miscarriage, premature
      delivery, gestational hypertension disease, gestational diabetes mellitus(GDM)in
      the foreign standard group had statistically significant differences (P < 0.05)
      when compared with the control group, respectively. While there was no
      statistically significant difference (P > 0.05) in the incidence of placental
      abruption or fetal distress. And the incidence of miscarriage, premature
      delivery, gestational hypertension disease, GDM in the national standard group
      had statistical significant difference (P < 0.05) compared with the control
      group, respectively. While there was no statistically significant difference (P >
      0.05) in the incidence of placental abruption or fetal distress. This study
      observed group of pregnant women's abortion, gestational hypertension disease,
      GDM incidence respectively compared with control group, the difference had
      statistical significance (P < 0.05); but in preterm labor, placental abruption,
      and fetal distress incidence, there were no statistically significant difference
      (P > 0.05). (4) The incidence of miscarriage, premature delivery, gestational
      hypertension disease, GDM, placental abruption, fetal distress in the TPO-Ab
      positive cases of the national standard group showed an increase trend when
      compared with TPO-Ab negative cases, with no statistically significant difference
      (P > 0.05). The incidence of gestational hypertension disease and GDM in the TPO
      Ab positive cases of the study observed group had statistical significance
      difference (P < 0.05) when compared with TPO-Ab negative cases; while the
      incidence of miscarriage, premature birth, placental abruption, fetal distress
      had no statistically significant difference (P > 0.05). The incidence of
      gestational hypertension disease and GDM in the TPO-Ab positive cases had
      statistically significance difference when compared with TPO-Ab negtive cases of
      foreign standard group (P < 0.05). CONCLUSIONS: (1) The incidence of subclinical
      hypothyroidism is rather high during early pregnancy and can lead to adverse
      pregnancy outcome. (2) Positive TPO-Ab result has important predictive value of
      the thyroid dysfunction and GDM. (3) Relatively, the ATA standard of diagnosis
      (serum TSH level> 2.50 mU/L) is safer for the antenatal care; the national
      standard (serum TSH level> 5.76 mU/L) is not conducive to pregnancy management.

PMID- 25603907
TI  - [Perspective study of urodynamic factors with pre- and post-operation overactive
      bladder symptoms for anterior vaginal prolapse].
AB  - OBJECTIVE: To identify pre-operative demographic and urodynamic (UD) parameters
      related to overactive bladder (OAB) symptoms of pre-operation and persistence of
      after pelvic organ prolapse (POP) repair. METHODS: From Jan 1, 2010 to Oct 31,
      2012, this perspective study examined demographic and UD data of 175 patients
      undergoing POP surgery. Pre- and post- operative urinary distress inventory 6
      (UDI- 6) scores for frequency and urge urinary incontinence (UUI) were analyzed,
      and correlations between scores and pre-operative UD data were also analyzed.
      RESULTS: (1)Surgery resulted in a improvement of frequency (71.0% , 71/100) and
      UUI (69.2% , 63/91) at 12-24 months follow-up. (2)Pre-operative UD parameters:
      first desire of bladder <100 ml, 6.3% (11/175); detrusor overactivity, 14.9%
      (26/175); post-void residual >=50 ml, 11.4% (20/175); maximal flow rate (Qmax),
      (16+/-7) ml/s. (3)Comparison of pre- operative UD datas between patients with OAB
      symptoms and without, with OAB symptoms group had more patients of type III
      stress urinary incontinence [5% (5/91) versus 0 (0/84), P = 0.022]. (4)Qmax was
      higher in improvement in UUI group than that in persistent UUI after POP repair
      [(17+/-7) ml/s versus (13+/-5) ml/s, P < 0.01]. CONCLUSIONS: POP repair
      significantly reduces OAB symptoms; however, there had not exact predictor for
      symptoms of persistent frequency, UUI after POP repair. Persistent UUI symptom
      may be related to Qmax of pre-operative UD.

PMID- 25603908
TI  - [Clinical application of perforator flap in extended radical vulvectomy of vulvar
      carcinoma].
AB  - OBJECTIVE: To evaluate the clinical application of perforator flap in extended
      radical vulvectomy of vulvar carcinoma. METHODS: Retrospectively, twelve cases of
      vulva carcinoma were treated by radical extensive excision, and the defects were
      repaired with perforator flap. RESULTS: All the flaps were survived and healed
      with first intention except one infection. The wound infection patient was
      treated with change of the dressing and antibiotics. The reconstructed vulvae
      were plump and elastic. It appeared like the normal vulvae and there was no
      contraction of the vagina. CONCLUSIONS: Vulvar reconstruction with the perforator
      flap after the radical vulvectomy could make the patients recover easily, which
      produces almost normal appearance and function of the vulvae, reduces the time of
      wound healing, the patient could get the next therapy more quickly and the
      quality of life improving. It has wide clinical application value.

PMID- 25603909
TI  - [Primary pelvic retroperitoneal tumors: clinical analysis of 36 cases].
AB  - OBJECTIVE: To explorer the diagnostic rationales for primary pelvic
      retroperitoneal tumors and summarize their clinical characteristics and
      treatments. METHODS: The clinicopathological data of total of 36 patients with
      primary pelvic retroperitoneal tumor, who visited Peking Union Medical Collage
      Hospital, Chinese Academy of Medical Sciences because of pelvic mass from January
      1986 and September 2013 were analysed retrospectively. And their clinical
      manifestations, accessory examination, surgical findings, postoperative
      pathological results and prognosis were summarized. RESULTS: Among the 36
      patients, twenty-nine cases were treated by gynecology department firstly, 7
      cases were treated by surgical department firstly. Only 7 cases complained
      abdominal expanding while others had no uncomfortable complains before the
      discovery of the tumor. Among 27 cases who took color Doppler ultrasonography
      examination, only 3 cases reminded that the tumors might come from the pelvic
      retroperitoneal space. CT and MRI results were respectively 6/16 and 3/6, that
      the tumor might come from the pelvic retroperitoneal space. The level of CA125 of
      18 cases were tested before the surgery: 17 out of 18 cases were normal or
      elevated lightly. The tumors of 8 cases were excised incompletely because of the
      blood vessels around the tumors and the close relationship between the tumors and
      the pelvic wall, while other's were excised completely. Among the 25 cases that
      had operation at the gynecological department, ten cases underwent operations
      collaboratively with surgical department; two cases had complications of urinary
      system injures. Postoperative pathological examinations revealed there were 28
      cases (78%, 28/36)with benign lesions including 11 schwannoma, 6 leiomyoma, 3
      teratoma, 1 lymphangioleiomyoma, 1 neurofibroma, 1 paraganglioma, 2 fibromatosis,
      1 aggressive angiomyxoma, 1 mucinous cystadenoma and 1 solitary fibrous tumor;
      and 8 cases(22% , 8/36)with malignant lesions including 3 leiomyosarcoma, 2
      liposarcoma, 2 adenocarcinoma and 1 squamous carcinoma. During the follow-up
      period, 28 cases whose tumors were excised completely had no recurrence. While, 3
      out of 8 cases excised incompletely recurred. CONCLUSIONS: Primary pelvic
      retroperitoneal tumors have no typical manifestations, CT and MRI are more
      accurate. Surgery is a key for retroperitoneal tumors. Considering the complexity
      of the anatomy of the pelvic retroperitoneal space and the resulted difficulties
      of the surgeries, multidisiciplinary cooperation is needed and important.

PMID- 25603910
TI  - [Cognition and attitude of postpartum contraception among obstetricians in
      Tianjin area].
AB  - OBJECTIVE: Through analysed the questionnaire about postpartum contraception
      knowledge-attitude-practice (KAP) among obstetricians, to understand the
      postpartum contraceptive knowledge, idea, attitude and related factors among
      obstetricians. METHODS: From October 2013 to December 2013, 209 obstetricians of
      10 different levels of the hospital of Tianjin area had been enrolled in this
      study, and KAP questionnaire was investigated. RESULTS: The knowledge of
      postpartum contraception among obstetricians was seriously lack, the total
      correct rate was 34.8%, the lowest score was 5 points, the highest was 80 points,
      the average score was 34.8+/-13.5, more than 60 points accounted for only 2.9%
      (6/209). 86.6% (181/209) obstetricians have thought it necessary to carry out
      postpartum contraceptive propaganda during pregnancy, and 97.6% (204/209)
      obstetricians have thought it necessary to develop postpartum contraception
      training. 92.8% (194/209) and 94.2% (197/209) obstetricians always informed that
      pay attention to contraception before discharge and postpartum visit, specific
      methods were not discussed. Obstetricians obtained relevant progress of
      contraceptive knowledge mainly through the daily medical work (92.8% , 194/209),
      hoped that approach postpartum contraception related knowlege through continuing
      education courses (77.5%, 162/209), special lectures in academic conference
      (72.2%, 151/209) and special training (67.5%, 141/209). CONCLUSIONS: (1) The
      postpartum contraception knowledge among obstetricians is seriously lack. (2) The
      obstetricians hold positive attitude towards the propaganda for postpartum
      contraceptive knowledge. (3) Postpartum contraception related education only
      provided before discharging and postpartum visit, and the content was simply
      inform that pay attention to contraception, specific methods are not discussed.
      (4) To explore the reason why postpartum contraception situation is not ideal,
      that's because insufficient attention and propaganda, obstetricians don't update
      the contraception knowledge, and be lack of knowledge on the efficient, long
      acting reversible contraception methods, exaggerated the side effects and
      complications.

PMID- 25603911
TI  - [Studies on the lymphatic tropism and lymph cells apoptosis of cisplatin-nano
      carbon suspension in the rats].
AB  - OBJECTIVE: To research the lymphatic tropism and lymph cell apoptosis of
      cisplatin-nano carbon suspension in rats with the aim of proposing a new way for
      chemotherapy. METHODS: A total of 72 Wistar rats were randomly divided into two
      groups. For the experimental group, cisplatin-nano carbon suspension 0.3 ml (4
      mg/ml) was injected subcutaneously into Wistar rats' plantar. For the control
      group, cisplatin 0.3 ml (4 mg/ml) was injected intravenously. Cisplatin
      concentration in the inguinal lymphatic tissue and plasma was determined by high
      performance liquid chromatography (HPLC) at 1, 2, 3, 4, 5 and 6 hours after drug
      administration. The apoptosis of lymph cell was detected by terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling
      assay (TUNEL). Targeting ability were evaluated and compared by targeting index
      (TI), selecting index (SI) and relative extraction efficiency (RE). SPSS 17.0
      statistical software was used to analyze the differentiation of the cisplatin
      concentration and apoptosis index (AI) among various groups. DAS software was
      used to evaluate the lymphatic tropism. RESULTS: The cisplatin concentration of
      lymphatic tissue in experimental group were respectively (1.03+/- 0.32), (3.00+/
      0.91), (2.20+/-0.73), (1.56+/-0.38), (1.30+/-0.74) and (0.78+/-0.34)ug/g after
      administration 1, 2, 3, 4, 5 and 6 hours, while in control group were (0.49+/
      0.21), (1.02+/-0.70), (0.59+/-0.50), (0.56+/-0.21), (0.47+/-0.18) and (0.36+/
      0.13)ug/g, in which there were significant difference at every times (all P <
      0.05)except at 1 hour(P = 0.173). The cisplatin concentration in plasma were
      significant higher in the experimental group than those in the control group at
      various times(all P < 0.05), the former were respectively (0.57+/-0.28), (1.22 +/
      0.45), (0.61 +/- 0.18), (0.51 +/- 0.13), (0.45 +/- 0.13) and (0.40 +/- 0.07)
      ug/ml, while the latter were respectively (3.12+/-0.33), (4.09+/-0.48), (2.56+/
      0.38), (2.05+/-0.13), (1.81+/-0.28) and (1.44+/-0.40) ug/ml. Values of TI were
      respectively 2.12, 2.93, 3.73, 2.78, 2.76 and 2.19 and SI were 1.80, 2.45, 3.63,
      3.07, 2.86 and 1.93. Value of RE was 2.86. The AI in experimental group were
      respectively (16.5+/-5.2)%, (30.2+/-2.8)%, (51.7 +/- 4.3)%, (69.8 +/- 3.2)%,
      (80.1 +/- 4.3)% and (89.7 +/- 8.5)% , while in control group were
      respectively(1.3+/-0.8)%, (2.4+/-1.7)%, (3.2+/-1.1)%, (3.9+/-2.6)%, (5.1+/-2.1)%
      and (6.3+/-2.3)%, in which there were significant difference at every points(all
      P < 0.05). CONCLUSIONS: The nano carbon has the character of lymphatic tropism,
      and could send cisplatin to lymphatic tissue to achieve a higher concentration.
      The trait may break a new way for chemotherapy targeting lymph metastasis.

PMID- 25603913
TI  - Reduced Responsiveness to Social Provocation in Autism Spectrum Disorder.
AB  - Deficits in emotion processing and social interaction are prominent symptoms of
      autism spectrum disorder (ASD). ASD has also been associated with aggressive
      tendencies towards self and others. The prevalence of aggressive behavior in this
      disorder, its etiology and its impact on social life are still unclear. This
      study investigated behavioral and physiological effects of social provocation in
      patients with ASD and healthy controls. We used a modified Taylor Aggression
      Paradigm in 24 high-functioning patients with ASD and 24 healthy controls.
      Participants were instructed to play against a fictitious human opponent. Money
      withdrawals toward the participant represented provocation and money deduction by
      the participant denoted aggressive behavior. Throughout the measurement,
      electrodermal activity (EDA) was recorded. Healthy controls showed higher
      aggressive responses to high provocation compared to low provocation, which
      demonstrated the effectiveness of the used procedure in eliciting aggression.
      Patients' responses were not influenced by the level of social provocation,
      although in both groups aggression was higher after lost compared to won trials.
      Physiologically, controls showed fewer but higher EDA amplitudes when responding
      aggressively, whereas patients displayed the opposite pattern of more but lower
      EDA amplitudes. The modified Taylor Aggression Paradigm successfully elicited
      aggression and revealed different behavioral and neurophysiological responses in
      patients and healthy controls. Patients' aggressive behavior as well as their
      physiological responses were less modulated by level of provocation compared to
      controls. Therapeutic attempts for patients might concentrate on improving
      empathic abilities and the understanding of social situations, including
      provocation and aggressive behavior.

PMID- 25603912
TI  - Low expression of chloride channel accessory 1 predicts a poor prognosis in
      colorectal cancer.
AB  - BACKGROUND: Chloride channel accessory 1 (CLCA1) is a CLCA protein that plays a
      functional role in regulating the differentiation and proliferation of colorectal
      cancer (CRC) cells. Here we investigated the relationship between the level of
      CLCA1 and the prognosis of CRC. METHODS: First, the level of CLCA1 was detected
      quantitatively in normal and cancerous colonic epithelial tissues with
      immunohistochemistry. Next, the correlations between CLCA1 expression,
      pathological tumor features, and the overall survival rate of patients was
      analyzed. Finally, 3 publicly available data sets from the Gene Expression
      Omnibus were examined: normal CRC versus early CRC (GSE4107), primary CRC versus
      metastatic lesions (GSE28702), and low chromosomal instability versus high
      chromosomal instability (GSE30540). RESULTS: The expression of CLCA1 was
      decreased markedly in tumor specimens. CLCA1 expression was correlated
      significantly with the histological grade (P < .01) and lymph node metastasis (P
      < .01). A significantly poorer overall survival rate was found in patients with
      low levels of CLCA1 expression versus those with high expression levels (P <
      .05). The results confirmed that the low expression of CLCA1 in CRC was highly
      associated with tumorigenesis, metastasis, and high chromosomal instability. In
      addition, the loss of CLCA1 disrupted the differentiation of human colon
      adenocarcinoma cells (Caco-2) in vitro. CONCLUSIONS: These findings suggest that
      CLCA1 levels may be a potential predictor of prognosis in primary human CRC. Low
      expression of CLCA1 predicts disease recurrence and lower survival, and this has
      implications for the selection of patients most likely to need and benefit from
      adjuvant chemotherapy.

PMID- 25603914
TI  - Program synergies and social relations: implications of integrating HIV testing
      and counselling into maternal health care on care seeking.
AB  - BACKGROUND: Women and children in sub-Saharan Africa bear a disproportionate
      burden of HIV/AIDS. Integration of HIV with maternal and child services aims to
      reduce the impact of HIV/AIDS. To assess the potential gains and risks of such
      integration, this paper considers pregnant women's and providers' perceptions
      about the effects of integrated HIV testing and counselling on care seeking by
      pregnant women during antenatal care in Tanzania. METHODS: From a larger
      evaluation of an integrated maternal and newborn health care program in Morogoro,
      Tanzania, this analysis included a subset of information from 203 observations of
      antenatal care and interviews with 57 providers and 190 pregnant women from 18
      public health centers in rural and peri-urban settings. Qualitative data were
      analyzed manually and with Atlas.ti using a framework approach, and quantitative
      data of respondents' demographic information were analyzed with Stata 12.0.
      RESULTS: Perceptions of integrating HIV testing with routine antenatal care from
      women and health providers were generally positive. Respondents felt that
      integration increased coverage of HIV testing, particularly among difficult-to
      reach populations, and improved convenience, efficiency, and confidentiality for
      women while reducing stigma. Pregnant women believed that early detection of HIV
      protected their own health and that of their children. Despite these positive
      views, challenges remained. Providers and women perceived opt out HIV testing and
      counselling during antenatal services to be compulsory. A sense of powerlessness
      and anxiety pervaded some women's responses, reflecting the unequal relations,
      lack of supportive communications and breaches in confidentiality between women
      and providers. Lastly, stigma surrounding HIV was reported to lead some women to
      discontinue services or seek care through other access points in the health
      system. CONCLUSION: While providers and pregnant women view program synergies
      from integrating HIV services into antenatal care positively, lack of supportive
      provider-patient relationships, lack of trust resulting from harsh treatment or
      breaches in confidentiality, and stigma still inhibit women's care seeking. As
      countries continue rollout of Option B+, social relations between patients and
      providers must be understood and addressed to ensure that integrated delivery of
      HIV counselling and services encourages women's care seeking in order to improve
      maternal and child health.

PMID- 25603915
TI  - Visual impairment is associated with physical and mental comorbidities in older
      adults: a cross-sectional study.
AB  - BACKGROUND: Visual impairment is common in older people and the presence of
      additional health conditions can compromise health and rehabilitation outcomes. A
      small number of studies have suggested that comorbities are common in visual
      impairment; however, those studies have relied on self-report and have assessed a
      relatively limited number of comorbid conditions. METHODS: We conducted a cross
      sectional analysis of a dataset of 291,169 registered patients (65-years-old and
      over) within 314 primary care practices in Scotland, UK. Visual impairment was
      identified using Read Code ever recorded for blindness and/or low vision (within
      electronic medical records). Prevalence, odds ratios (from prevalence rates
      standardised by stratifying individuals by age groups (65 to 69 years; 70 to 74;
      75 to 79; 80 to 84; and 85 and over), gender and deprivation quintiles) and 95%
      confidence intervals (95% CI) of 37 individual chronic physical/mental health
      conditions and total number of conditions were calculated and compared for those
      with visual impairment to those without. RESULTS: Twenty seven of the 29 physical
      health conditions and all eight mental health conditions were significantly more
      likely to be recorded for individuals with visual impairment compared to
      individuals without visual impairment, after standardising for age, gender and
      social deprivation. Individuals with visual impairment were also significantly
      more likely to have more comorbidities (for example, five or more conditions
      (odds ratio (OR) 2.05 95% CI 1.94 to 2.18)). CONCLUSIONS: Patients aged 65 years
      and older with visual impairment have a broad range of physical and mental health
      comorbidities compared to those of the same age without visual impairment, and
      are more likely to have multiple comorbidities. This has important implications
      for clinical practice and for the future design of integrated services to meet
      the complex needs of patients with visual impairment, for example, embedding
      depression and hearing screening within eye care services.

PMID- 25603916
TI  - Outbreaks of meningococcal B infection and the 4CMenB vaccine: historical and
      future perspectives.
AB  - Strains of Neisseria meningitidis serogroup B (MenB) causing invasive
      meningococcal disease are genetically diverse; however, only a small number of
      hyperinvasive lineages (CC32, CC41/44, CC269 and CC162) have dominated during the
      global spread over the past 50 years. Since the mid-1970s, major outbreaks and
      hyperendemic disease have been reported in Norway, Cuba, France, Canada, New
      Zealand (and elsewhere), most recently in the USA. We characterized the
      epidemiology of these MenB outbreaks and their associated clonal complexes and
      retrospectively assessed the potential coverage offered by the 4CMenB vaccine, a
      four-component vaccine developed to help confer protection against a broad range
      of meningococcal B strains causing disease. Of 21 isolates from four clonal
      complexes evaluated using both human Serum Bactericidal Assay and the
      Meningococcal Antigen Testing System, coverage ranged from 67 to 100%. 4CMenB
      shows good potential as a candidate vaccine to be used in the control of new MenB
      outbreaks globally. 

PMID- 25603917
TI  - "I felt sad and did not enjoy life": Cultural context and the associations
      between anhedonia, depressed mood, and momentary emotions.
AB  - The meanings of "anhedonia" and "depressed mood," the cardinal emotional symptoms
      of major depression, may be shaped by cultural norms regarding pleasure and
      sadness. Thirty-two European Americans, 26 Hispanic Americans, 33 Asian
      Americans, and 20 Russian Americans provided reports of (a) depressive symptoms,
      (b) momentary emotions and pleasure, and (c) global subjective well-being.
      Momentary reports were collected over 10 days using handheld personal digital
      assistants. Reports of anhedonia were associated with heightened levels of
      momentary low arousal negative emotions (e.g., sadness), whereas reports of
      depressed mood were associated with dampened levels of momentary positive
      emotions (e.g., happiness). Symptoms of anhedonia and depressed mood interacted
      in their associations with momentary pleasure. In addition, the associations of
      anhedonia and depressed mood with positive emotions and life satisfaction
      differed across cultural groups. Specifically, these symptoms were associated
      with dampened positive emotions in the Asian American group only. Additionally,
      anhedonia was associated with dampened global life satisfaction in the European
      American group only. These results suggest that reports of anhedonia and
      depressed mood cannot be interpreted at face value as specific and culture-free
      indicators of emotional deficits. Instead, they appear to signal changes in the
      balance of positive and negative emotions, with the exact nature of these signals
      shaped at least in part by cultural context. This conclusion has important
      consequences for the clinical interpretation of depressive symptoms in
      multicultural societies. 

PMID- 25603919
TI  - Correction.

PMID- 25603920
TI  - Stimulus-parity synaesthesia (1893, 2014): introducing a 'forgotten' subtype.

PMID- 25603918
TI  - Body composition and bone health in long-term survivors of acute lymphoblastic
      leukaemia in childhood and adolescence: the protocol for a cross-sectional cohort
      study.
AB  - INTRODUCTION: Success in the treatment of young people with cancer, as measured
      conventionally by survival rates, is mitigated by late effects of therapy that
      impose a burden of morbidity and limit life expectancy. Among these adverse
      sequelae are altered body composition, especially obesity, and compromised bone
      health in the form of osteoporosis and increased fragility. These outcomes are
      potentially reversible and even preventable. This study will examine measures of
      body composition and bone health in long-term survivors of acute lymphoblastic
      leukaemia (ALL) in childhood and adolescence. These measures will be complemented
      by measures of physical activity and health-related quality of life (HRQL).
      METHODS AND ANALYSIS: Survivors of ALL who are at least 10 years from diagnosis,
      following treatment on uniform protocols, will undergo measurements of body mass
      index; triceps skin fold thickness and mid-upper arm circumference; fat mass,
      lean body mass, skeletal muscle mass and bone mineral density by dual energy X
      ray absorptiometry; trabecular and cortical bone indices and muscle density by
      peripheral quantitative CT; physical activity by the Habitual Activity Estimation
      Scale; and HRQL by Health Utilities Index instruments. Descriptive measures will
      be used for continuous variables and number (percent) for categorical variables.
      Associations between variables will be assessed using Fisher's exact t test and
      the chi(2) test; correlations will be tested by the Pearson correlation
      coefficient. ETHICS AND DISSEMINATION: The study is approved by the institutional
      research ethics board and is supported by a competitive funding award.
      Dissemination of the results will occur by presentations to scientific meetings
      and publications in peer-reviewed journals, and by posting summaries of the
      results on websites accessed by adolescent and young adult survivors of cancer.

PMID- 25603921
TI  - OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in
      bone.
AB  - Dormant disseminated tumour cells can be detected in the bone marrow of breast
      cancer patients several years after resection of the primary tumour. The majority
      of these patients will remain asymptomatic, however, ~ 15% will go on to develop
      overt bone metastases and this condition is currently incurable. The reason why
      these dormant cells are stimulated to proliferate and form bone tumours in some
      patients and not others remains to be elucidated. We have recently shown that in
      an in vivo model, increasing bone turnover by ovariectomy stimulated
      proliferation of disseminated tumour cells, resulting in formation of bone
      metastasis. We now show for the first time that osteoclast mediated mechanisms
      induce growth of tumours from dormant MDA-MB-231 cells disseminated in the bone.
      We also show that disruption of RANK-RANKL interactions following administration
      of OPG-Fc inhibits growth of these dormant tumour cells in vivo. Our data support
      early intervention with anti-resorptive therapy in a low-oestrogen environment to
      prevent development of bone metastases.

PMID- 25603922
TI  - Understanding the factors that influence breast reconstruction decision making in
      Australian women.
AB  - BACKGROUND: Breast reconstruction is safe and improves quality of life. Despite
      this, many women do not undergo breast reconstruction and the reasons for this
      are poorly understood. This study aims to identify the factors that influence a
      woman's decision whether or not to have breast reconstruction and to better
      understand their attitudes toward reconstruction. METHODOLOGY: An online survey
      was distributed to breast cancer patients from Breast Cancer Network Australia.
      Results were tabulated, described qualitatively and analyzed for significance
      using a multiple logistic regression model. RESULTS: 501 mastectomy patients
      completed surveys, of which 62% had undergone breast reconstruction. Factors that
      positively influenced likelihood of reconstruction included lower age, bilateral
      mastectomy, access to private hospitals, decreased home/work responsibilities,
      increased level of home support and early discussion of reconstructive options.
      Most common reasons for avoiding reconstruction included "I don't feel the need"
      and "I don't want more surgery". The most commonly sited sources of
      reconstruction information came from the breast surgeon followed by the plastic
      surgeon then the breast cancer nurse and the most influential of these was the
      plastic surgeon. CONCLUSIONS: A model using factors easily obtained on clinical
      history can be used to understand likelihood of reconstruction. This knowledge
      may help identify barriers to reconstruction, ultimately improving the
      clinicians' ability to appropriately educate mastectomy patients and ensure
      effective decision making around breast reconstruction.

PMID- 25603925
TI  - Modulation of benzene or naphthalene binding to palladium cluster sites by the
      backside-ligand effect.
AB  - The backside-ligand modulation strategy to enhance the substrate binding property
      of Pd clusters is reported. The benzene or naphthalene binding ability of Pd3 or
      Pd4 clusters is enhanced significantly by the backside cyclooctatetraene ligand,
      leading to the formation of the first solution-stable benzene- or naphthalene Pd
      clusters. The present results imply that the ligand design of the metal clusters,
      especially for the backside ligand of the metal cluster site, is crucial to
      acquire a desired reactivity of metal clusters. 

PMID- 25603924
TI  - Autologously generated tissue-engineered bone flaps for reconstruction of large
      mandibular defects in an ovine model.
AB  - The reconstruction of large craniofacial defects remains a significant clinical
      challenge. The complex geometry of facial bone and the lack of suitable donor
      tissue often hinders successful repair. One strategy to address both of these
      difficulties is the development of an in vivo bioreactor, where a tissue flap of
      suitable geometry can be orthotopically grown within the same patient requiring
      reconstruction. Our group has previously designed such an approach using tissue
      chambers filled with morcellized bone autograft as a scaffold to autologously
      generate tissue with a predefined geometry. However, this approach still required
      donor tissue for filling the tissue chamber. With the recent advances in
      biodegradable synthetic bone graft materials, it may be possible to minimize this
      donor tissue by replacing it with synthetic ceramic particles. In addition, these
      flaps have not previously been transferred to a mandibular defect. In this study,
      we demonstrate the feasibility of transferring an autologously generated tissue
      engineered vascularized bone flap to a mandibular defect in an ovine model, using
      either morcellized autograft or synthetic bone graft as scaffold material. 

PMID- 25603926
TI  - The "phosphorus pyramid": a visual tool for dietary phosphate management in
      dialysis and CKD patients.
AB  - Phosphorus retention plays a pivotal role in the onset of mineral and bone
      disorders (MBD) in chronic kidney disease (CKD). Phosphorus retention commonly
      occurs as a result of net intestinal absorption exceeding renal excretion or
      dialysis removal. The dietary phosphorus load is crucial since the early stages
      of CKD, throughout the whole course of the disease, up to dialysis-dependent end
      stage renal disease.Agreement exits regarding the need for dietary phosphate
      control, but it is quite challenging in the real-life setting. Effective
      strategies to control dietary phosphorus intake include restricting phosphorus
      rich foods, preferring phosphorus sourced from plant origin, boiling as the
      preferred cooking procedure and avoiding foods with phosphorus-containing
      additives. Nutritional education is crucial in this regard.Based on the existing
      literature, we developed the "phosphorus pyramid", namely a novel, visual, user
      friendly tool for the nutritional education of patients and health-care
      professionals. The pyramid consists of six levels in which foods are arranged on
      the basis of their phosphorus content, phosphorus to protein ratio and phosphorus
      bioavailability. Each has a colored edge (from green to red) that corresponds to
      recommended intake frequency, ranging from "unrestricted" to "avoid as much as
      possible".The aim of the phosphorus pyramid is to support dietary counseling in
      order to reduce the phosphorus load, a crucial aspect of integrated CKD-MBD
      management. 

PMID- 25603927
TI  - Bullying, internalized hepatitis (Hepatitis C virus) stigma, and self-esteem:
      Does spirituality curtail the relationship in the workplace.
AB  - The objective of this study was to examine the impact of workplace bullying on
      self-esteem, including the mediating effect of internalized stigma and the
      moderating effect of spirituality, among hepatitis C virus patients. Data were
      collected from 228 employed hepatitis C virus patients who had been admitted to
      Gastroenterology and Hepatology wards in Pakistani hospitals. We found support
      for the hypothesis that workplace bullying is associated with low self-esteem via
      internalized stigma. In addition, spirituality moderated the association such
      that participants with greater spirituality were buffered from the impact of
      stigma on self-esteem.

PMID- 25603928
TI  - Resilience as a mediator in emotional social support's relationship with
      occupational psychology health in firefighters.
AB  - This study's objective is to examine the relationship between emotional demands
      and emotional social support at work, and the impact of resilience on health. A
      cross-sectional study of 156 firefighters was conducted. Descriptive analyses of
      the study's variables were performed, along with structural equation analysis and
      hierarchical regression analysis. The results suggest statistically significant
      relationships among the study's variables. Social support from one's boss and
      intense emotional demands were found to have an interaction effect on
      firefighters' resilience. The findings confirm the mediating role of resilience
      and the relationship with emotional social support from the boss on firefighters'
      occupational health.

PMID- 25603929
TI  - Willingness to provide support for a quit attempt: A study of partners of
      smokers.
AB  - Support from close others predicts smoking abstinence, yet little research has
      investigated what factors promote support. This study investigates predictors of
      support for a quit attempt. Partners of smokers (N = 131) reported their
      relationship quality, concern for partner's health, own smoking status, and
      intended support for a quit attempt. Smokers were less supportive than were
      nonsmokers. Relationship quality, concern for partners' health, and motivation to
      quit were positively associated, and nicotine dependence was negatively
      associated, with intended support. The findings suggest that support for smoking
      cessation depends on one's own smoking behaviors as well as characteristics of
      the relationship.

PMID- 25603930
TI  - Environmental Transmission Electron Microscopy Study of Diesel Carbon Soot
      Combustion under Simulated Catalytic-Reaction Conditions.
AB  - Environmental transmission electron microscopy (ETEM) is used to monitor the
      catalytic combustion of diesel carbon soot upon exposure to molecular oxygen at
      elevated temperatures by using a gas-injection specimen heating holder. The
      reaction conditions simulated in the ETEM experiments reconstruct real conditions
      effectively. This study demonstrated for the first time that soot combustion
      occurs at the soot-catalyst interface for both Ag/CeO2 and Cu/BaO/La2 O3
      catalysts. 

PMID- 25603931
TI  - Progesterone and Wnt4 control mammary stem cells via myoepithelial crosstalk.
AB  - Ovarian hormones increase breast cancer risk by poorly understood mechanisms. We
      assess the role of progesterone on global stem cell function by serially
      transplanting mouse mammary epithelia. Progesterone receptor (PR) deletion
      severely reduces the regeneration capacity of the mammary epithelium. The PR
      target, receptor activator of Nf-kappaB ligand (RANKL), is not required for this
      function, and the deletion of Wnt4 reduces the mammary regeneration capacity even
      more than PR ablation. A fluorescent reporter reveals so far undetected perinatal
      Wnt4 expression that is independent of hormone signaling. Pubertal and adult Wnt4
      expression is specific to PR+ luminal cells and requires intact PR signaling.
      Conditional deletion of Wnt4 reveals that this early, previously unappreciated,
      Wnt4 expression is functionally important. We provide genetic evidence that
      canonical Wnt signaling in the myoepithelium required PR and Wnt4, whereas the
      canonical Wnt signaling activities observed in the embryonic mammary bud and in
      the stroma around terminal end buds are independent of Wnt4. Thus, progesterone
      and Wnt4 control stem cell function through a luminal-myoepithelial crosstalk
      with Wnt4 acting independent of PR perinatally.

PMID- 25603932
TI  - The mRNA decay factor PAT1 functions in a pathway including MAP kinase 4 and
      immune receptor SUMM2.
AB  - Multi-layered defense responses are activated in plants upon recognition of
      invading pathogens. Transmembrane receptors recognize conserved pathogen
      associated molecular patterns (PAMPs) and activate MAP kinase cascades, which
      regulate changes in gene expression to produce appropriate immune responses. For
      example, Arabidopsis MAP kinase 4 (MPK4) regulates the expression of a subset of
      defense genes via at least one WRKY transcription factor. We report here that
      MPK4 is found in complexes in vivo with PAT1, a component of the mRNA decapping
      machinery. PAT1 is also phosphorylated by MPK4 and, upon flagellin PAMP
      treatment, PAT1 accumulates and localizes to cytoplasmic processing (P) bodies
      which are sites for mRNA decay. Pat1 mutants exhibit dwarfism and de-repressed
      immunity dependent on the immune receptor SUMM2. Since mRNA decapping is a
      critical step in mRNA turnover, linking MPK4 to mRNA decay via PAT1 provides
      another mechanism by which MPK4 may rapidly instigate immune responses. 

PMID- 25603933
TI  - miR-290/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote
      pluripotency.
AB  - Enhanced glycolysis is a main feature of pluripotent stem cells (PSCs) and is
      proposed to be important for the maintenance and induction of pluripotency. The
      molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using
      Dgcr8-/- mouse embryonic stem cells (ESCs) that lack mature miRNAs, we found that
      miR-290 cluster of miRNAs stimulates glycolysis by upregulating glycolytic
      enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency
      during reprogramming. Mechanistically, we identified Mbd2, a reader for
      methylated CpGs, as the target of miR-290 cluster that represses glycolysis and
      reprogramming. Furthermore, we discovered Myc as a key target of Mbd2 that
      controls metabolic switch in ESCs. Importantly, we demonstrated that miR-371
      cluster, a human homolog of miR-290 cluster, stimulates glycolysis to promote the
      reprogramming of human fibroblasts. Hence, we identified a previously
      unappreciated mechanism by which miR-290/371 miRNAs orchestrate epigenetic,
      transcriptional and metabolic networks to promote pluripotency in PSCs and during
      reprogramming.

PMID- 25603934
TI  - Anti-A2 and anti-A1 domain antibodies are potential predictors of immune
      tolerance induction outcome in children with hemophilia A.
AB  - BACKGROUND: Hemophilia A (HA) is a congenital bleeding disorder resulting from
      factor VIII deficiency. The most serious complication of HA management is the
      appearance of inhibitory antibodies (Abs) against injected FVIII concentrates. To
      eradicate inhibitors, immune tolerance induction (ITI) is usually attempted, but
      it fails in up to 30% of cases. Currently, no undisputed predictive marker of ITI
      outcome is available to facilitate the clinical decision. OBJECTIVES: To identify
      predictive markers of ITI efficacy. METHODS: The isotypic and epitopic
      repertoires of inhibitory Abs were analyzed in plasma samples collected before
      ITI initiation from 15 children with severe HA and high-titer inhibitors, and
      their levels were compared in the two outcome groups (ITI success [n = 7] and ITI
      failure [n = 8]). The predictive value of these candidate biomarkers and of the
      currently used indicators (inhibitor titer and age at ITI initiation, highest
      inhibitor titer before ITI, and interval between inhibitor diagnosis and ITI
      initiation) was then compared by statistical analysis (Wilcoxon test and receiver
      receiver operating characteristic [ROC] curve analysis). RESULTS: Whereas current
      indicators seemed to fail in discriminating patients in the two outcome groups
      (ITI success or failure), anti-A1 and anti-A2 Ab levels before ITI initiation
      appeared to be good potential predictive markers of ITI outcome (P < 0.018). ROC
      analysis showed that anti-A1 and anti-A2 Abs were the best at discriminating
      between outcome groups (area under the ROC curve of > 0.875). CONCLUSION: Anti-A1
      and anti-A2 Abs could represent new promising tools for the development of ITI
      outcome prediction tests for children with severe HA.

PMID- 25603937
TI  - Workplace cohort studies in times of economic instability.
AB  - BACKGROUND: A prospective study directed to musculoskeletal health in the
      manufacturing workforce. METHODS: A 36-month longitudinal study using mixed
      method; surveys with work and non-work psychosocial variables, physiologic
      measurements physical performance, interviews and focus groups, and direct
      observation of work activity. RESULTS: Changing economic conditions introduced
      barriers requiring recruiting a larger number of study sites. Study adherence was
      unexpectedly high. Coincident with their economic concerns, participants
      perceived an increase in workplace stress, but not physical demand. New
      instruments were added to assess economic effects on retirement planning and the
      physical and emotional costs of caregiving responsibilities. CONCLUSIONS: The
      economic conditions required adaptive alterations in design due to workforce
      volatility but presented opportunities for studying the link between working
      conditions and health. Nevertheless, study size expectations were met through an
      adaptive approach that suggests a potential effect of the economy on health and
      well-being.

PMID- 25603935
TI  - Investing in prospective cohorts for etiologic study of occupational exposures.
AB  - Prospective cohorts have played a major role in understanding the contribution of
      diet, physical activity, medical conditions, and genes to the development of many
      diseases, but have not been widely used for occupational exposures. Studies in
      agriculture are an exception. We draw upon our experience using this design to
      study agricultural workers to identify conditions that might foster use of
      prospective cohorts to study other occupational settings. Prospective cohort
      studies are perceived by many as the strongest epidemiologic design. It allows
      updating of information on exposure and other factors, collection of biologic
      samples before disease diagnosis for biomarker studies, assessment of effect
      modification by genes, lifestyle, and other occupational exposures, and
      evaluation of a wide range of health outcomes. Increased use of prospective
      cohorts would be beneficial in identifying hazardous exposures in the workplace.
      Occupational epidemiologists should seek opportunities to initiate prospective
      cohorts to investigate high priority, occupational exposures.

PMID- 25603938
TI  - Mortality of older construction and craft workers employed at department of
      energy (DOE) nuclear sites: follow-up through 2011.
AB  - BACKGROUND: The Building Trades National Medical Screening Program (BTMed) was
      established in 1996 to provide occupational medicine screening examinations for
      construction workers who have worked at US Department of Energy nuclear sites.
      Workers participating in BTMed between 1998 and 2011 were followed to determine
      their vital status and mortality experience through December 31, 2011. METHODS:
      The cohort includes 18,803 BTMed participants and 2,801 deaths. Cause-specific
      Standardized Mortality Ratios (SMRs) were calculated based on US death rates.
      RESULTS: Mortality was elevated for all causes, all cancers, cancers of the
      trachea, bronchus, and lung and lymphatic and hematopoietic system, mesothelioma,
      COPD, and asbestosis. CONCLUSIONS: Construction workers employed at DOE sites
      have a significantly increased risk for occupational illnesses. Risks are
      associated with employment during all time periods covered including after 1980.
      The cancer risks closely match the cancers identified for DOE compensation from
      radiation exposures. Continued medical surveillance is important.

PMID- 25603936
TI  - Overview of the National Occupational Mortality Surveillance (NOMS) system:
      leukemia and acute myocardial infarction risk by industry and occupation in 30 US
      states 1985-1999, 2003-2004, and 2007.
AB  - BACKGROUND: Cancer and chronic disease are leading causes of death in the US with
      an estimated cost of $46 billion. METHODS: We analyzed 11 million cause-specific
      deaths of US workers age 18-64 years in 30 states during 1985-1999, 2003-2004,
      and 2007 by occupation, industry, race, gender, and Hispanic origin. RESULTS: The
      highest significantly elevated proportionate leukemia mortality was observed in
      engineers, protective service, and advertising sales manager occupations and in
      banks/savings &loans/credit agencies, public safety, and public administration
      industries. The highest significantly elevated smoking-adjusted acute myocardial
      infarction mortality was noted in industrial and refractory machinery mechanics,
      farmers, mining machine operators, and agricultural worker occupations; and
      wholesale farm supplies, agricultural chemical, synthetic rubber, and
      agricultural crop industries. CONCLUSIONS: Significantly elevated risks for acute
      myocardial infarction and leukemia were observed across several occupations and
      industries that confirm existing reports and add new information. Interested
      investigators can access the NOMS website at
      http://www.cdc.gov/niosh/topics/NOMS/.

PMID- 25603939
TI  - Characteristics of nonfatal occupational injuries among U.S. workers with and
      without disabilities.
AB  - BACKGROUND: Workers with disabilities have a higher risk of nonfatal occupational
      injuries than workers without disabilities. The characteristics of these injuries
      are not well described. METHODS: Using 1997-2011 National Health Interview Survey
      (NHIS) data, we compared the nonfatal occupational injuries sustained by U.S.
      workers with and without disabilities. RESULTS: Overexertion or strenuous
      movements and falls accounted for 56.7% of all occupational injuries in workers
      with disabilities, compared with 45.6% in workers without a disability. Workers
      with disabilities were more frequently injured in the lower extremity (32.3% vs.
      26.6%) or torso (22.9% vs. 16.9%). Workers with disabilities sustained more
      unspecified injuries (13.5% vs. 7.9%) and fewer open wound injuries (15.7% vs.
      24.2%) than their counterparts without a disability. CONCLUSIONS: U.S. workers
      with disabilities had a higher rate of occupational injuries and these injuries
      tended to be more severe and were more likely to be caused by overexertion/
      strenuous movement or falls.

PMID- 25603940
TI  - Why do farmworkers delay treatment after debilitating injuries? Thematic analysis
      explains if, when, and why farmworkers were treated for injuries.
AB  - BACKGROUND: Farmworkers who delay treatment after workplace injuries may increase
      injury severity and experience longer recovery times. To understand why
      farmworkers delay treatment we employed a mixed-methods analysis of 393
      farmworker injury narratives from the National Agricultural Workers Survey
      (NAWS). METHODS: First, open-ended injury narratives were coded for attitudes
      related to injury timing and delay. Next, narratives were compared against
      demographic survey attributes to assess contextual information and patterns
      linked to treatment timing. RESULTS: Four treatment timings were identified:
      immediate medical treatment (57.9%), delayed medical treatment (18.2%) self-
      administered treatment (14.9%), and no treatment at all (8.9%). Delay was
      primarily attributed to attitudes prioritizing work over pain, and when workers
      were able to work despite injury. However, immediate treatment was sought when
      workers were completely debilitated and unable to work, when a supervisor was
      notified, or when exposed to pesticides during injury. Timing choices varied by
      education, gender and migrant status. CONCLUSIONS: Training on timely treatment,
      including notification of supervisors, may help reduce treatment delay for
      farmworkers.

PMID- 25603941
TI  - Evaluating a county-based healthy nail salon recognition program.
AB  - OBJECTIVES: The City of San Francisco, California established a recognition
      program for nail salons that use safer nail products and receive worker safety
      training. This pilot study examined whether participating salons had reduced
      levels of toluene, methyl methacrylate (MMA), and total volatile organic
      compounds (TVOC), and improved knowledge and behavior compared to control salons.
      METHODS: We conducted personal air monitoring and administered surveys assessing
      knowledge and behaviors of two workers from each of six intervention salons and
      five control salons. We conducted assessments before and after the worker
      training. RESULTS: Although non-significant, there was a reduction in toluene (
      46% vs. 0%) and TVOC (-19% vs. +47%), but an increase in MMA (+113% and +72%)
      among intervention salons compared to control salons. Awareness of dibutyl
      phthalates in nail products increased (+55%) among intervention salons between
      surveys. CONCLUSIONS: A government-administered nail salon recognition program
      may reduce chemical exposures and increase work-related knowledge.

PMID- 25603943
TI  - Investigating obesity among professional drivers: the high risk professional
      driver study.
AB  - OBJECTIVE: The aim of this study is to detect the main individual and
      transportation factors associated with obesity and its prevalence among Italian
      professional drivers (PDs). METHODS: We performed a cross-sectional questionnaire
      survey. Data from PDs (n = 497) were used for analyses. RESULTS: Sixty-one
      percent of participants were either overweight or obese according to their body
      mass index. Predictive factors for obesity were traveling more than 40,000 miles
      per year (odds ratio [OR] 4.20, confidence interval [CI] 1.41-12.56) and hours
      spent behind the wheel per day (OR 1.27, CI 1.02-1.58). Bus drivers had half the
      risk of being obese compared to truck drivers (OR 0.45, CI 0.23-0.87). An inverse
      association was detected between educational attainment and obesity (OR 0.32, CI
      0.11-0.90). CONCLUSIONS: PDs with high number of driving hours per day, miles
      driven per year, and low educational level should be subject to special
      educational programs to reduce and prevent obesity.

PMID- 25603942
TI  - Characterizing occupational heat-related mortality in the United States, 2000
      2010: an analysis using the Census of Fatal Occupational Injuries database.
AB  - BACKGROUND: Occupational heat-related mortality is not well studied and risk
      factors remain largely unknown. This paper describes the epidemiological
      characteristics of heat-related deaths among workers in the US 2000-2010.
      METHODS: Fatality data were obtained at the Bureau of Labor Statistics from the
      confidential on-site Census of Fatal Occupational Injuries database. Fatality
      rates and risk ratios with 95% confidence intervals were calculated by year, sex,
      age group, ethnicity, race, state, and industry. RESULTS: Between 2000 and 2010,
      359 occupational heat-related deaths were identified in the U.S., for a yearly
      average fatality rate of 0.22 per 1 million workers. Highest rates were found
      among Hispanics, men, the agriculture and construction industries, the state of
      Mississippi, and very small establishments. CONCLUSIONS: This study provides the
      first comprehensive national profile of heat-related deaths in the U.S.
      workplace. Prevention efforts should be directed at small businesses and at
      industries and individuals with the highest risk.

PMID- 25603945
TI  - Working overtime and risk factors for coronary heart disease: a propensity score
      analysis based in the J-SHINE (Japanese Study of Stratification, Health, Income,
      and Neighborhood) study.
AB  - BACKGROUND: Evidence on the causal relationship between working overtime and the
      risk of coronary heart disease is limited. METHODS: We surveyed 2355 workers in
      Japan and conducted propensity-matched logistic regression analysis, using
      propensity-matched 438 pairs, to evaluate the associations between working
      overtime (more than 50 hr per week) and coronary risk factors: physical
      inactivity, cigarette smoking, sleep deprivation (<5 hr/day), psychological
      stress, overweight/obesity, and excessive alcohol consumption. The exposure and
      outcomes were self-reported. RESULTS: Among 2355 workers, 476 participants worked
      overtime. Propensity-matched analysis revealed that the associations between
      working overtime and sleep deprivation (odds ratios (OR) and 95% confidence
      intervals: 2.33, 1.39-3.88) and high stress (2.13, 1.60-2.82). The associations
      between working overtime and physical inactivity, current smoking, and
      overweight/obesity were not statistically significant. Excessive alcohol
      consumption was inversely associated with working overtime. CONCLUSIONS: Working
      overtime was positively associated with two coronary risk factors: sleep
      deprivation and increased psychological stress.

PMID- 25603944
TI  - Development and validation of a fatigue assessment scale for U.S. construction
      workers.
AB  - OBJECTIVE: To develop a fatigue assessment scale and test its reliability and
      validity for commercial construction workers. METHODS: Using a two-phased
      approach, we first identified items (first phase) for the development of a
      Fatigue Assessment Scale for Construction Workers (FASCW) through review of
      existing scales in the scientific literature, key informant interviews (n = 11)
      and focus groups (three groups with six workers each) with construction workers.
      The second phase included assessment for the reliability, validity, and
      sensitivity of the new scale using a repeated-measures study design with a
      convenience sample of construction workers (n = 144). RESULTS: Phase one resulted
      in a 16-item preliminary scale that after factor analysis yielded a final 10-item
      scale with two sub-scales ("Lethargy" and "Bodily Ailment"). During phase two,
      the FASCW and its subscales demonstrated satisfactory internal consistency (alpha
      coefficients were FASCW [0.91], Lethargy [0.86] and Bodily Ailment [0.84]) and
      acceptable test-retest reliability (Pearson Correlations Coefficients: 0.59-0.68;
      Intraclass Correlation Coefficients: 0.74-0.80). Correlation analysis
      substantiated concurrent and convergent validity. A discriminant analysis
      demonstrated that the FASCW differentiated between groups with arthritis status
      and different work hours. CONCLUSIONS: The 10-item FASCW with good reliability
      and validity is an effective tool for assessing the severity of fatigue among
      construction workers.

PMID- 25603946
TI  - Construction of an antimyoglobin single-chain variable fragment with rapid
      reaction kinetics.
AB  - Antibodies with rapid reaction kinetics (high association and dissociation
      rates), named reversible antibodies, are used to perform continuous monitoring of
      sensitive disease biomarkers. In cases of acute myocardial infarction (AMI),
      continuous monitoring and early diagnosis are important. Human myoglobin (Myo) is
      a useful biomarker for AMI during the early stage after the onset of symptoms. In
      this study, a single-chain variable fragment (scFv) specific to Myo was derived
      from an IgG antibody that has rapid reaction kinetics. Enzyme-linked
      immunosorbent assay revealed that recombinant scFv exhibited 3.8-fold reduced
      affinity compared with the parent IgG antibody based on the antibody
      concentration necessary for 50% of the maximum signal. The scFv retained the
      rapid reaction kinetic mode with average kon and koff of 2.63 * 10(5) M(-1) Sec(
      1) and 3.25 * 10(-3) Sec(-1) , respectively, which were reduced to 10- and 2.3
      fold compared with those of the parent antibody. The equilibrium constant for the
      association of the scFv (KA = 8.09 * 10(7) M(-1) ) was 4.6-fold lower than that
      of its parent IgG antibody. This scFv may be a starting point for further
      mutagenesis/kinetic and structural analyses providing valuable insight into the
      mechanism of reversible antibodies. 

PMID- 25603947
TI  - Dentate total molecular layer interneurons mediate cannabinoid-sensitive
      inhibition.
AB  - Activity of the dentate gyrus, which gates information flow to the hippocampus,
      is under tight inhibitory regulation by interneurons with distinctive axonal
      projections, intrinsic and synaptic characteristics and neurochemical identities.
      Total molecular layer cells (TML-Cs), a class of morphologically distinct
      GABAergic neurons with axonal projections across the molecular layer, are among
      the most frequent interneuronal type in the dentate subgranular region. However,
      little is known about their synaptic and neurochemical properties. We demonstrate
      that synapses from morphologically identified TML-Cs to dentate interneurons are
      characterized by low release probability, facilitating short-term dynamics and
      asynchronous release. TML-Cs consistently show somatic and axonal labeling for
      the cannabinoid receptor type 1 (CB1 R) yet fail to express cholecystokinin (CCK)
      indicating their distinctive neurochemical identity. In paired recordings, the
      release probability at synapses between TML-Cs was increased by the CB1 R
      antagonist AM251, demonstrating baseline endocannabinoid regulation of TML-C
      synapses. Apart from defining the synaptic and neurochemical features of TML-Cs,
      our findings reveal the morphological identity of a class of dentate CB1 R
      positive neurons that do not express CCK. Our findings indicate that TML-Cs can
      mediate cannabinoid sensitive feed-forward and feedback inhibition of dentate
      perforant path inputs.

PMID- 25603948
TI  - Screening and comorbidity of clinical levels of fear of cancer recurrence.
AB  - PURPOSE: The prevalence of clinical levels of fear of cancer recurrence (FCR) in
      cancer survivors is unknown, which may be partly explained by the lack of an
      assessment method that would make it possible to distinguish between normal and
      clinical levels of FCR. Moreover, despite the apparent overlap between FCR and
      manifestations of some psychiatric disorders, no study has yet evaluated the
      comorbidity of clinical levels of FCR. The goals of this study were to assess the
      capacity of the Fear of Cancer Recurrence Inventory severity subscale, to
      consider a shorter form of the FCRI (FCRI-SF), to screen for clinical levels of
      FCR, and to assess its psychiatric comorbidity. METHODS: Sixty French-Canadian
      cancer survivors (73% of those eligible) who had been treated within the past 4
      years for localized breast, prostate, lung, or colorectal cancer were randomly
      selected. Participants were administered a clinical interview assessing FCR, the
      Structured Clinical Interview for DSM-IV, and self-report scales. RESULTS: A
      cutoff score of 13 or higher on the FCRI-SF was associated with optimal
      sensitivity (88%) and specificity (75%) rates for the screening of clinical
      levels of FCR. Cancer survivors with clinical levels of FCR were significantly
      more likely to meet the criteria for a current psychiatric disorder (60%) than
      patients with nonclinical levels (29%). Anxiety disorders tended to be the most
      common comorbid disorders. CONCLUSIONS/IMPLICATIONS FOR CANCER SURVIVORS: The
      FCRI-SF allows rapid and effective screening of clinical levels of FCR, a
      condition associated with significant psychiatric comorbidity.

PMID- 25603949
TI  - The association between partner support and psychological distress among prostate
      cancer survivors in a nationwide study.
AB  - PURPOSE: Up to 38% of prostate cancer survivors experience significant
      psychological distress; 6-16% are diagnosed with depression or anxiety disorders.
      Support from a relationship partner can ameliorate psychological distress, but
      many studies treat relationship status as a dichotomous predictor without
      accounting for level of support provided by the partner. METHODS: The current
      study is a secondary analysis of a sample of 292 prostate cancer survivors
      recruited by nine Community Clinical Oncology Program (CCOP) sites around the USA
      to a larger randomized controlled trial. Self-reported distress was measured at a
      baseline visit using the Profile of Mood States (POMS) and partner support was
      measured using the Social Network and Support Assessment (SNSA). Post hoc groups
      consisting of unmarried survivors, married survivors with low partner support
      (SNSA scores below the median), and married survivors with high partner support
      (SNSA scores above the median) were compared on distress using univariate and
      analysis of covariance (ANCOVA) analyses. RESULTS: Married prostate cancer
      survivors with high partner support reported significantly lower levels of
      psychological distress than the other two groups on the total distress scale
      (16.20-19.19 points lower, p < 0.001). After adjusting for multiple comparisons,
      this pattern was also seen for subscales of distress. CONCLUSIONS: This study
      highlights the importance of assessing both partner support and marital status
      when evaluating a survivor's psychosocial functioning and support network.
      IMPLICATIONS FOR CANCER SURVIVORS: Assessing support could improve understanding
      of the association between partner support and prostate cancer survivors'
      psychological distress and could lead to interventions to bolster support and
      reduce distress.

PMID- 25603951
TI  - Sentinel lymph node biopsy in breast cancer: the role of micrometastasis.
AB  - Intraoperative sentinel lymph node biopsy is widely used in patients with early
      stage breast cancer for staging the axilla. The conventional analysis of the SLN
      has classically been performed by frozen section or touch imprint with a rapid
      H&E (hematoxylin and eosin) staining. Because of the risk of false-negative
      results, it has been replaced by the one-step acid amplification (OSNA) assay, a
      molecular diagnostic assay for the detection of cytokeratin 19 mRNA expression.
      Due to the controversial for the use of OSNA to evaluate the SLN because of its
      cost-effective and the lack of consensus to perform or avoid a lymphadenectomy
      when there is micrometastasis, we analyze 410 patients subjected to SLN biopsy in
      Hospital Puerta de Hierro, Madrid (Spain). Of the total of nodes, 223 (54.4 %)
      were processed throughout frozen-section examination and imprint cytology and 187
      (45.6 %) throughout OSNA. The specificity of the frozen-section histological
      examination was of 100 %, with a sensitivity of 83.33 % (95 % CI 73.07-93.60). Of
      the 40 patients with definitive micrometastasis in the SLN, axillary dissection
      was performed in 90 % of the patients, with subsequent positive affectation in
      four of them (11.11 %). Based on our result and taking into account that 10 % of
      the lymphadenectomy performed after micrometastasis are positive, we do not
      believe that lymphadenectomy should be avoided after N(mi+) is detected in a SLN.

PMID- 25603950
TI  - Association of RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies.
AB  - The receptor for advanced glycation end products (RAGE), a member of
      immunoglobulin superfamily, has been proved to stimulate survival, growth, and
      metastatic spread of cancers cells. Evidence suggested that the 82G/S, -374T/A,
      and -429T/C polymorphisms in RAGE promoter region might affect the risk of
      cancer; however, data from epidemiological studies showed conflicting results
      that remain to be further clarified. This meta-analysis was performed to derive a
      more precise estimation of 82G/S, -374T/A, and -429T/C polymorphisms and risk of
      cancer. A comprehensive electronic search was conducted for articles published up
      until December 2, 2014, in Medline (PubMed), Embase, the Cochrane Library and
      Google Scholar. A total of 12 case-control articles were included in this meta
      analysis, providing 3,374 cases and 3,757 controls for 82G/S, 2,936 cases and
      3,338 controls for -374T/A, and 2,882 cases and 3,279 controls for -429T/C
      specifically. The pooled odds ratio (OR) with 95 % confidence interval (CI) was
      calculated to evaluate the associations with risk of cancer. Overall, we observed
      significantly increased risk of cancer in relation to 82G/S (A vs. G: OR 1.321,
      95 % CI 1.164-1.499, P het 0.028; AA vs. GG: OR 1.823, 95 % CI 1.541-2.157, P het
      < 0.001; AG vs. GG: OR 1.399, 95 % CI 1.120-1.746, P het 0.002; GA+AA vs. GG: OR
      1.470, 95 % CI 1.187-1.821, P het 0.002; AA vs. GG+AG: OR 1.416, 95 % CI 1.158
      1.732, P het 0.107) and reduced risk of cancer in relation to -374T/A (AA vs. TT:
      OR 0.818, 95 % CI 0.686-0.976, P het 0.025; A vs. T: OR 0.908, 95 % CI 0.840
      0.981, P het 0.014). In subgroup analysis for 82G/S, a significantly elevated
      cancer risk was indicated in the population of Asian and patients with lung
      cancer, and for -374T/A, reduced risk was indicated in population of Caucasian
      and patients with lung cancer and breast cancer. But no significant association
      was observed between -429T/C and risk of cancer. Thus, this meta-analysis
      revealed that 82G/S polymorphism is associated with a significantly increased
      risk of cancer, while -374T/A polymorphism is associated with a reduced risk of
      cancers. 

PMID- 25603952
TI  - Exosomal Hsp70 mediates immunosuppressive activity of the myeloid-derived
      suppressor cells via phosphorylation of Stat3.
AB  - Myeloid-derived suppressor cells (MDSCs), one of the main cell populations, are
      responsible for regulating the immune response, which accumulates in tumor
      bearing mice and humans contributing to cancer development. Exosomes produced by
      tumor cells have been involved in tumor-associated immune suppression. However,
      the role of exosomes is unclear in the activation of MDSCs. Here, we have
      purified tumor-derived exosomes from the supernatants of Renca cell cultures.
      Transmission electron microscopy was used to confirm their morphology, and
      Western blot analysis showed that Hsp70 was rich in these isolated exosomes
      compared with the whole-cell lysates of Renca cells. Then, we demonstrated that
      there was a more powerful activity of exosomal Hsp70-mediated induction of
      proinflammation cytokines, tumor growth factors of MDSCs and tumor progression
      than exosomes pre-incubated with anti-Hsp70 antibody. Furthermore, we show that
      an interactive exosomal HSP70 and MDSCs determine the suppressive activity of the
      MDSCs via phosphorylation of Stat3 (p-Stat3). Finally, we show that exosomal
      Hsp70 triggers p-Stat3 in MDSCs in a TLR2-MyD88-dependent manner. Meanwhile, we
      also find that there is a more significant increase in the percentage of CD11b+Gr
      1+ cells in the mice, which are treated with exosomal Hsp70 than that exosomes
      pre-incubated with anti-Hsp70 antibody. Hence, we believe that the signaling
      pathway activation by exosomal Hsp70 within MDSCs may be a significant target in
      future treatment of renal cell carcinoma. 

PMID- 25603954
TI  - Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a
      10-year nationwide retrospective study.
AB  - OBJECTIVE: Outcome after intrauterine transfusions due to severe hemolytic
      disease of the fetus and newborn. DESIGN: Nationwide population-based
      retrospective cohort study. SETTING: All women treated with intrauterine
      transfusions for hemolytic disease of the fetus and newborn in Finland in 2003
      2012. POPULATION: 339 intrauterine transfusions, performed in 104 pregnancies of
      84 women. METHODS: Information on antenatal screening of red cell antibodies and
      red cell units issued for intrauterine transfusion was obtained from the Finnish
      Red Cross Blood Service database, and obstetric and neonatal data from hospital
      records. MAIN OUTCOME MEASURES: Procedure-related complications, perinatal
      mortality, neonatal morbidity. RESULTS: Overall survival was 94.2% (95%
      confidence interval 89.7-98.7). There were four fetal and two neonatal deaths.
      Procedure-related fetal loss rate was 1.2% (95% confidence interval 0.04-2.4) per
      procedure and 3.8% (95% confidence interval 0.1-7.5) per pregnancy. Of the four
      procedure-related losses, three were due to technically difficult intrauterine
      transfusions causing infection and preterm birth. Of the live born infants, 19%
      (95% confidence interval 11.3-26.7) were born before 32 weeks' gestation. The
      incidence of severe neonatal morbidity (respiratory distress syndrome, severe
      cerebral injury, sepsis) was 22.2% (95% confidence interval 13.4-30.2). Poor
      outcome (death, severe neonatal morbidity) was negatively associated with
      gestational age at first transfusion (p = 0.001) and at birth (p = 0.00006).
      Follow-up of the infants was too incomplete to assess the neurodevelopmental
      outcome. CONCLUSIONS: Although overall survival is comparable with previous
      studies, our concern is procedure-related infections and preterm births. Close
      collaboration between the university hospitals is needed to ensure timely
      treatment, operator skills and systematic follow-up of the children.

PMID- 25603953
TI  - Efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with
      bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the
      treatment of non-small cell lung cancer: a systematic review and meta-analysis.
AB  - The meta-analysis evaluated the efficacy and safety of chemotherapy or tyrosine
      kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine
      kinase inhibitors alone in the treatment of non-small cell lung cancer (NSCLC).
      The PubMed/MEDLINE, Ovid, Web of Science, CNKI, and the Cochrane Library database
      were searched for eligible randomized controlled trials comparing the combination
      of chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors
      (EGFR-TKIs) with bevacizumab to chemotherapy or EGFR-TKI alone. Main outcome
      measures were overall survival (OS), progression-free survival (PFS), objective
      response rate (ORR), and adverse effects. The pooled data were analyzed by STATA
      12.0 and expressed as hazard ratio (HR) or risk ratio (RR), with their
      corresponding 95 % confidence intervals (95 % CI). Nine eligible trials
      comprising 3,547 patients (1,779 for bevacizumab and 1,768 for controls) were
      included in the study. Chemotherapy or TKIs in combination with bevacizumab
      significantly prolonged PFS (HRpfs 0.72, 95 % CIpfs 0.66-0.79, P pfs < 0.001) and
      OS (HRos 0.90, 95 % CIos 0.82-0.99, P os = 0.029) as first-line treatment for
      NSCLC compared with chemotherapy or TKIs alone. Bevacizumab combination regimens
      significantly prolonged PFS (HR 0.62, 95 % CI 0.52-0.74, P < 0.001) as second
      line treatment; however, no benefit regarding OS was observed with the addition
      of bevacizumab (HR 0.94, 95 % CI 0.78-1.12, P = 0.479). The bevacizumab group
      showed increased ORR in both first- and second-line treatments. The high-dose
      bevacizumab subgroup in combination with chemotherapy showed a statistically
      significant improvement in OS, PFS, and ORR (HRos 0.89, 95 % CIos 0.80-0.99, P os
      0.037; HRpfs 0.71, 95 % CIpfs 0.64-0.79, P pfs < 0.01, RRorr 1.85, 95 % CIorr
      1.59-2.15, P orr < 0.001, respectively); however, the low-dose bevacizumab
      subgroup did not show enhanced OS (HRos 0.91, 95 % CIos 0.77-1.07, P os = 0.263),
      and a moderate improvement of PFS and ORR (HRpfs 0.85, 95 % CIpfs 0.72-1.00, P
      pfs = 0.049; RRorr 1.60, 95 % CIorr 1.28-2.0, P orr < 0.001). Erlotinib in
      combination with bevacizumab significantly prolonged PFS (HR 0.60, P < 0.001, 95
      % CI 0.51-0.71) and increased ORR (RR 1.21, 95 % CI 0.98-1.49, P = 0.067)
      compared with erlotinib alone. A higher incidence of grade >=3 adverse events
      such as proteinuria, hypertension, and hemorrhage was observed in the bevacizumab
      combination group than in the control group without bevacizumab (P all < 0.05).
      The addition of bevacizumab to chemotherapy or erlotinib can significantly
      improve PFS and ORR both in first- and second-line treatments of advanced NSCLC,
      with an acceptable risk of bleeding events, hypertension, proteinuria, and rash.
      Combination therapy with bevacizumab and chemotherapy is beneficial regarding OS;
      however, whether bevacizumab plus erlotinib can prolong OS need further
      validation. 

PMID- 25603956
TI  - Structural and electronic properties of an ordered grain boundary formed by
      separated (1,0) dislocations in graphene.
AB  - We present an investigation of the structural and electronic properties of an
      ordered grain boundary (GB) formed by separated pentagon-heptagon pairs in single
      layer graphene/SiO2 using scanning tunneling microscopy/spectroscopy (STM/STS),
      coupled with density functional theory (DFT) calculations. It is observed that
      the pentagon-heptagon pairs, i.e., (1,0) dislocations, form a periodic quasi-one
      dimensional chain. The (1,0) dislocations are separated by 8 transverse rows of
      carbon rings, with a period of ~2.1 nm. The protruded feature of each dislocation
      shown in the STM images reflects its out-of-plane buckling structure, which is
      supported by the DFT simulations. The STS spectra recorded along the small-angle
      GB show obvious differential-conductance peaks, the positions of which
      qualitatively accord with the van Hove singularities from the DFT calculations. 

PMID- 25603955
TI  - (99m)Tc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in
      inflammation.
AB  - Non-invasive imaging of the inflammatory process can provide great insight into a
      wide variety of disease states, aiding diagnosis, evaluation and effective
      targeted treatment. During inflammation, blood borne leukocytes are recruited,
      through a series of activation and adhesion steps, to the site of injury or
      infection where they migrate across the blood vessel wall into the tissue. Thus,
      tracking leukocyte recruitment and accumulation provides a dynamic and localised
      read out of inflammatory events. Current leukocyte imaging techniques require ex
      vivo labelling of patient blood, involving laborious processing and potential
      risks to both patient and laboratory staff. Utilising high affinity ligands for
      leukocyte specific receptors may allow for injectable tracers that label
      leukocytes in situ, omitting potentially hazardous ex vivo handling. Formyl
      peptide receptors (FPRs) are a group of G-protein coupled receptors involved in
      the chemotaxis and inflammatory functioning of leukocytes. Highly expressed on
      leukocytes, and up-regulated during inflammation, these receptors provide a
      potential target for imaging inflammatory events. Herein we present the synthesis
      and initial in vitro testing of a potential Single Photon Emission Computed
      Tomography (SPECT) leukocyte tracer. The FPR1 antagonist cFLFLFK-NH2, which
      displays high affinity with little physiological effect, has been linked via a
      PEG motif to a (99m)Tc chelate. This tracer shows in vitro binding to human
      embryonic kidney cells expressing the FPR1 receptor, and functional in vitro
      tests reveal cFLFLFK-NH2 compounds to have no effect on inflammatory cell
      functioning. Overall, these data show that (99m)Tc.cFLFLFK-NH2 may be a useful
      tool for non-invasive imaging of leukocyte accumulation in inflammatory disease
      states. 

PMID- 25603958
TI  - Probing the Mott physics in kappa-(BEDT-TTF)2X salts via thermal expansion.
AB  - In the field of interacting electron systems the Mott metal-to-insulator (MI)
      transition represents one of the pivotal issues. The role played by lattice
      degrees of freedom for the Mott MI transition and the Mott criticality in a
      variety of materials are current topics under debate. In this context, molecular
      conductors of the kappa-(BEDT-TTF)2X type constitute a class of materials for
      unraveling several aspects of the Mott physics. In this review, we present a
      synopsis of literature results with focus on recent expansivity measurements
      probing the Mott MI transition in this class of materials. Progress in the
      description of the Mott critical behavior is also addressed. 

PMID- 25603957
TI  - KCNQ1 channel modulation by KCNE proteins via the voltage-sensing domain.
AB  - The gating of the KCNQ1 potassium channel is drastically regulated by auxiliary
      subunit KCNE proteins. KCNE1, for example, slows the activation kinetics of KCNQ1
      by two orders of magnitude. Like other voltage-gated ion channels, the opening of
      KCNQ1 is regulated by the voltage-sensing domain (VSD; S1-S4 segments). Although
      it has been known that KCNE proteins interact with KCNQ1 via the pore domain,
      some recent reports suggest that the VSD movement may be altered by KCNE. The
      altered VSD movement of KCNQ1 by KCNE proteins has been examined by site-directed
      mutagenesis, the scanning cysteine accessibility method (SCAM), voltage clamp
      fluorometry (VCF) and gating charge measurements. These accumulated data support
      the idea that KCNE proteins interact with the VSDs of KCNQ1 and modulate the
      gating of the KCNQ1 channel. In this review, we will summarize recent findings
      and current views of the KCNQ1 modulation by KCNE via the VSD. In this context,
      we discuss our recent findings that KCNE1 may alter physical interactions between
      the S4 segment (VSD) and the S5 segment (pore domain) of KCNQ1. Based on these
      findings from ourselves and others, we propose a hypothetical mechanism for how
      KCNE1 binding alters the VSD movement and the gating of the channel. 

PMID- 25603959
TI  - Facile synthesis of ultrathin bimetallic PtSn wavy nanowires by nanoparticle
      attachment as enhanced hydrogenation catalysts.
AB  - Ultrathin wavy nanowires represent an emerging class of nanostructures that
      exhibit unique catalytic, magnetic, and electronic properties, but the controlled
      production of bimetallic wavy nanowires remains a significant challenge.
      Ultrathin bimetallic PtSn nanowires have been prepared with high yield and
      featuring a highly wavy structure. Owing to the ultrathin nature and unique
      electronic properties of these PtSn wavy nanowires, they exhibit improved
      catalytic performance for the hydrogenation of nitrobenzene, as well as for the
      hydrogenation of styrene. These results suggest a new strategy to prepare highly
      active catalysts through defect engineering and can significantly impact broad
      practical applications. 

PMID- 25603960
TI  - Sacral nerve stimulation for faecal incontinence and constipation: a European
      consensus statement.
AB  - AIM: In Europe during the last decade sacral nerve stimulation (SNS) or sacral
      neuromodulation (SNM) has been used to treat faecal incontinence (FI) and
      constipation. Despite this, there is little consensus on baseline investigations,
      patient selection and operative technique. A modified Delphi process was
      conducted to seek consensus on the current practice of SNS/SNM for FI and
      constipation. METHOD: A systematic literature search of SNS for FI and
      constipation was conducted using PubMed. A set of questions derived from the
      search and expert opinion were answered on-line on two occasions by an
      international panel of specialists from Europe. A 1-day face-to-face meeting of
      the experts finalized the discussion. RESULTS: Three hundred and ninety-three
      articles were identified from the literature search, of which 147 fulfilled the
      inclusion criteria. Twenty-two specialists in FI and constipation from Europe
      participated. Agreement was achieved on 43 (86%) of 50 domains including the set
      up of service, patient selection, baseline investigations, operative technique
      and programming of the device. The median of agreement was 95% (35-100%).
      CONCLUSION: Consensus was achieved on the majority of domains of SNS/SNM for FI
      and constipation. This should serve as a benchmark for safe and quality practice
      of SNS/SNM in Europe.

PMID- 25603961
TI  - Non-invasive blood haemoglobin and plethysmographic variability index during
      brachial plexus block.
AB  - BACKGROUND: Plethysmographic measurement of haemoglobin concentration ([Formula:
      see text]), pleth variability index (PVI), and perfusion index (PI) with the
      Radical-7 apparatus is growing in popularity. Previous studies have indicated
      that [Formula: see text] has poor precision, particularly when PI is low. We
      wanted to study the effects of a sympathetic block on these measurements.
      METHODS: Twenty patients underwent hand surgery under brachial plexus block with
      one Radical-7 applied to each arm. Measurements were taken up to 20 min after the
      block had been initiated. Venous blood samples were also drawn from the non
      blocked arm. RESULTS: During the last 10 min of the study, [Formula: see text]
      had increased by 8.6%. The PVI decreased by 54%, and PI increased by 188% in the
      blocked arm (median values). All these changes were statistically significant. In
      the non-blocked arm, these parameters did not change significantly. CONCLUSIONS:
      Brachial plexus block significantly altered [Formula: see text], PVI, and PI,
      which indicates that regional nervous control of the arm greatly affects
      plethysmographic measurements obtained by the Radical-7. After the brachial
      plexus block, [Formula: see text] increased and PVI decreased.

PMID- 25603962
TI  - On-chip monitoring of chemical syntheses in microdroplets via surface-enhanced
      Raman spectroscopy.
AB  - Conducting organic syntheses in microfluidic chips allows studying and optimising
      chemical reactions at minimal time-scales and resource consumption. Herein, we
      describe a multi-channel microdroplet chip, which allows fast and directed
      dispensing of reactants into individual droplets in a segmented flow. This gives
      access to study the reaction progress in situ via surface-enhanced Raman
      spectroscopic monitoring of fast moving individual droplets. This opens up new
      avenues for high-throughput screening of organic reactions at the micro- and nano
      scale. 

PMID- 25603964
TI  - A tachycardia showing marked T-wave changes after its termination.

PMID- 25603963
TI  - On the contribution of KCC2 and carbonic anhydrase to two types of in vitro
      interictal discharge.
AB  - GABAA receptor-mediated inhibition--which is due to Cl(-) and HCO3 (-) currents
      controlled by KCC2 and carbonic anhydrase activity, respectively--contributes to
      short- and long-lasting interictal events recorded from the CA3 region of
      hippocampus during application of 4-aminopyridine (4AP, 50 MUM). Here, we
      employed field potential recordings in an in vitro brain slice preparation to
      establish the effects induced by the KCC2 blockers VU0240551 (10 MUM) or
      bumetanide (50 MUM) and by the carbonic anhydrase inhibitor acetazolamide (10
      MUM) on the two types of interictal events. We found that blocking KCC2 activity
      decreased the amplitude of the short-lasting events. In addition, this
      pharmacological procedure increased the interval of occurrence of the long
      lasting events and reduced their amplitude. Blocking carbonic anhydrase activity
      with acetazolamide reduced the interval of occurrence and the duration of the
      short-lasting events while increasing their amplitude; acetazolamide also reduced
      the duration and amplitude of the long-lasting events. Finally, blocking either
      KCC2 or carbonic anhydrase activity increased the interval of occurrence of
      pharmacologically isolated synchronous GABAergic events and decreased their
      duration and amplitude. These data substantiate further the role of GABAA
      receptor-mediated signaling in driving neuronal populations toward
      hypersynchronous states presumably by increasing extracellular [K(+)].

PMID- 25603966
TI  - Effects of salinity and ascorbic acid on growth, water status and antioxidant
      system in a perennial halophyte.
AB  - Salinity causes oxidative stress in plants by enhancing production of reactive
      oxygen species, so that an efficient antioxidant system, of which ascorbic acid
      (AsA) is a key component, is an essential requirement of tolerance. However,
      antioxidant responses of plants to salinity vary considerably among species.
      Limonium stocksii is a sub-tropical halophyte found in the coastal marshes from
      Gujarat (India) to Karachi (Pakistan) but little information exists on its salt
      resistance. In order to investigate the role of AsA in tolerance, 2-month-old
      plants were treated with 0 (control), 300 (moderate) and 600 (high) mM NaCl for
      30 days with or without exogenous application of AsA (20 mM) or distilled water.
      Shoot growth of unsprayed plants at moderate salinity was similar to that of
      controls while at high salinity growth was inhibited substantially. Sap
      osmolality, AsA concentrations and activities of AsA-dependant antioxidant
      enzymes increased with increasing salinity. Water spray resulted in some
      improvement in growth, indicating that the growth promotion by exogenous
      treatments could partly be attributed to water. However, exogenous application of
      AsA on plants grown under saline conditions improved growth and AsA dependent
      antioxidant enzymes more than the water control treatment. Our data show that AsA
      dependent antioxidant enzymes play an important role in salinity tolerance of L.
      stocksii. 

PMID- 25603967
TI  - Suppression of annual Bromus tectorum by perennial Agropyron cristatum: roles of
      soil nitrogen availability and biological soil space.
AB  - Worldwide, exotic invasive grasses have caused numerous ecosystem perturbations.
      Rangelands of the western USA have experienced increases in the size and
      frequency of wildfires largely due to invasion by the annual grass Bromus
      tectorum. Rehabilitation of invaded rangelands is difficult; but long-term
      success is predicated on establishing healthy and dense perennial grass
      communities, which suppress B. tectorum. This paper reports on two experiments to
      increase our understanding of soil factors involved in suppression. Water was not
      limiting in this study. Growth of B. tectorum in soil conditioned by and
      competing with the exotic perennial Agropyron cristatum was far less relative to
      its growth without competition. When competing with A. cristatum, replacing a
      portion of conditioned soil with fresh soil before sowing of B. tectorum did not
      significantly increase its growth. The ability of conditioned soil to suppress B.
      tectorum was lost when it was separated from growing A. cristatum. Soil that
      suppressed B. tectorum growth was characterized by low mineral nitrogen (N)
      availability and a high molar ratio of [Formula: see text] in the solution-phase
      pool of [Formula: see text] Moreover, resin availability of [Formula: see text]
      explained 66 % of the variability in B. tectorum above-ground mass, attesting to
      the importance of A. cristatum growth in reducing N availability to B. tectorum.
      Trials in which B. tectorum was suppressed the most were characterized by very
      high shoot/root mass ratios and roots that have less root hair growth relative to
      non-suppressed counterparts, suggesting co-opting of biological soil space by the
      perennial grass as another suppressive mechanism. Greater understanding of the
      role of biological soil space could be used to breed and select plant materials
      with traits that are more suppressive to invasive annual grasses. 

PMID- 25603965
TI  - A mutualistic endophyte alters the niche dimensions of its host plant.
AB  - Mutualisms can play important roles in influencing species coexistence and
      determining community composition. However, few studies have tested whether such
      interactions can affect species distributions by altering the niches of partner
      species. In subalpine meadows of the Rocky Mountains, USA, we explored whether
      the presence of a fungal endophyte (genus Epichloe) may shift the niche of its
      partner plant, marsh bluegrass (Poa leptocoma) relative to a closely related but
      endophyte-free grass species, nodding bluegrass (Poa reflexa). Using observations
      and a 3-year field experiment, we tested two questions: (i) Do P. leptocoma and
      P. reflexa occupy different ecological niches? and (ii) Does endophyte presence
      affect the relative fitness of P. leptocoma versus P. reflexa in the putative
      niches of these grass species? The two species were less likely to co-occur than
      expected by chance. Specifically, P. leptocoma grew closer to water sources and
      in wetter soils than P. reflexa, and also had higher root colonization by
      mycorrhizal fungi. Endophyte-symbiotic P. leptocoma seeds germinated with greater
      frequency in P. leptocoma niches relative to P. reflexa niches, whereas neither
      endophyte-free (experimentally removed) P. leptocoma seeds nor P. reflexa seeds
      showed differential germination between the two niche types. Thus, endophyte
      presence constrained the germination and early survival of host plants to
      microsites occupied by P. leptocoma. However, endophyte-symbiotic P. leptocoma
      ultimately showed greater growth than endophyte-free plants across all
      microsites, indicating a net benefit of the symbiosis at this life history stage.
      Differential effects of endophyte symbiosis on different host life history stages
      may thus contribute to niche partitioning between the two congeneric plant
      species. Our study therefore identifies a symbiotic relationship as a potential
      mechanism facilitating the coexistence of two species, suggesting that symbiont
      effects on host niche may have community-level consequences. 

PMID- 25603968
TI  - Plant performance on Mediterranean green roofs: interaction of species-specific
      hydraulic strategies and substrate water relations.
AB  - Recent studies have highlighted the ecological, economic and social benefits
      assured by green roof technology to urban areas. However, green roofs are very
      hostile environments for plant growth because of shallow substrate depths, high
      temperatures and irradiance and wind exposure. This study provides experimental
      evidence for the importance of accurate selection of plant species and substrates
      for implementing green roofs in hot and arid regions, like the Mediterranean
      area. Experiments were performed on two shrub species (Arbutus unedo L. and
      Salvia officinalis L.) grown in green roof experimental modules with two
      substrates slightly differing in their water retention properties, as derived
      from moisture release curves. Physiological measurements were performed on both
      well-watered and drought-stressed plants. Gas exchange, leaf and xylem water
      potential and also plant hydraulic conductance were measured at different time
      intervals following the last irrigation. The substrate type significantly
      affected water status. Arbutus unedo and S. officinalis showed different
      hydraulic responses to drought stress, with the former species being
      substantially isohydric and the latter one anisohydric. Both A. unedo and S.
      officinalis were found to be suitable species for green roofs in the
      Mediterranean area. However, our data suggest that appropriate choice of
      substrate is key to the success of green roof installations in arid environments,
      especially if anisohydric species are employed. 

PMID- 25603969
TI  - Automated analysis of respiratory behavior in extremely preterm infants and
      extubation readiness.
AB  - BACKGROUND: Rates of extubation failure of extremely preterm infants remain high.
      Analysis of breathing patterns variability during spontaneous breathing under
      endotracheal tube continuous positive airway pressure (ETT-CPAP) is a potential
      tool to predict extubation readiness. OBJECTIVE: To investigate if automated
      analysis of respiratory signals would reveal differences in respiratory behavior
      between infants that were successfully extubated or not. METHODS: Respiratory
      Inductive Plethysmography (RIP) signals were recorded during ETT-CPAP just prior
      to extubation. Signals were digitized, and analyzed using an Automated
      Unsupervised Respiratory Event Analysis (AUREA). Extubation failure was defined
      as reintubation within 72 hr. Statistical differences between infants who were
      successfully extubated or failed were calculated. RESULTS: A total of 56 infants
      were enrolled and one was excluded due to instability during the ETT-CPAP; 11 out
      of 55 infants studied failed extubation (20%). No differences in demographics
      were observed between the success and failure groups. Significant differences on
      the variability of some respiratory parameters or 'metrics' estimated by AUREA
      were observed between the 2 groups. Indeed, a simple classification using the
      variability of two metrics of respiratory behavior predicted extubation failure
      with high accuracy. CONCLUSION: Automated analysis of respiratory behavior during
      a short ETT-CPAP period may help in the prediction of extubation readiness in
      extremely preterm infants.

PMID- 25603970
TI  - Chronic cheilitis caused by acrylates used as an adhesive for an orthodontic
      brace.

PMID- 25603971
TI  - Acute and chronic menisco-capsular separation in the young athlete: diagnosis,
      treatment and results in thirty seven consecutive patients.
AB  - PURPOSE: Menisco-capsular separation (MCS) is an avulsion type of injury of the
      medial and/or lateral meniscus and is defined as detachment of the meniscus from
      its capsular attachment. The aims of this study were to show the results of
      arthroscopic all-inside menisco-capsular repair in a large number of consecutive
      patients with acute or chronic MCS, emphasise the advantages of this safe
      treatment option and stress the superiority of the treatment on the basis of
      thorough physical examination of the knee joint over magnetic resonance imaging
      (MRI) diagnosis in MCS. METHODS: We evaluated data of patients treated between
      October 2011 and July 2012. Inclusion and exclusion criteria were defined and
      demographic variables evaluated. All patients were examined physically and with
      MRI. Knee arthroscopy was performed and the MCS repaired through all-inside
      menisco-capsular repair. Postoperative treatment was standardised. Patients were
      followed up for at least 24 weeks. RESULTS: Thirty-seven athletes (12 women, 25
      men) were evaluated. Only in six patients was MCS detected on MRI. In all
      patients, MCS was diagnosed via physical examination. Arthroscopic treatment led
      to significant (p < 0.01) improvement. There were no complications reported
      postoperatively. CONCLUSION: Isolated MCS is not as rare a meniscus pathology
      after trauma in young athletes as could be expected after reviewing current
      literature. It is occult on MRI scans in most of the cases and should therefor be
      taken into consideration in patients with acute or chronic tenderness at the
      level of the joint line and negative MRI scans. Thorough physical examination has
      higher diagnostic value than MRI alone, as shown in this study. Treatment of MCS
      using all-inside nonabsorbable sutures, as described in this study using Ultra
      FasT Fix(r), is effective if performed by an experienced surgeon.

PMID- 25603972
TI  - Acute and chronic injuries among senior international rowers: a cross-sectional
      study.
AB  - PURPOSE: The aim of the study was to define the types of musculoskeletal injuries
      present in senior international rowers. According to the literature, no such
      study has been performed in this group. METHODS: Injury data were obtained from a
      total of 634 rowers (33 % female, 67 % male) who completed a 12-month
      retrospective questionnaire on injury incidence while participating in the Senior
      World Rowing Championships in Munich, Germany, in 2007. RESULTS: The mean injury
      rate per one year was 0.92 injuries per rower (1.75 injuries per 1,000 training
      sessions per rower). The vast majority of self-reported injuries were chronic
      injuries (acute vs chronic ratio was 1:2.63), and the majority of reported
      injuries did not result in loss of time from training or competition. Of all
      acute injuries, 58.1 % were sustained during rowing-specific training, with 20.6
      % injuries sustained in the gym and 21.3 % during cross-training. The most common
      site of injury was the low back followed by the knee and the chest/thoracic
      spine. Senior open weight rowers who sustained chronic injuries achieved
      significantly better final ranking at the 2007 Senior World Rowing Championships
      compared to the same group of rowers who did not sustain any injury. CONCLUSION:
      Senior international rowers participating in World Rowing Championships sustained
      predominantly chronic (overuse) injuries during the rowing season studied. Those
      were mainly low severity injuries, with the low back being the most frequently
      injured site. This study may will help in prevention and early diagnosis of
      eventual injuries in top-level rowers.

PMID- 25603973
TI  - Higher reliability and validity of Baba classification with computerised
      tomography imaging and implant information for periprosthetic femoral fractures.
AB  - PURPOSE: Baba classification for periprosthetic femoral fracture focuses on the
      positional relationship between the implant design and fracture site. The
      objective of this study was to investigate whether the addition of CT images and
      implant information to plain radiograms increases the reliability of Baba
      classification to a level higher than that of Vancouver classification. METHODS:
      Twenty patients were randomly selected from 61 patients with periprosthetic
      femoral fracture between 2009 and 2014. After Vancouver and Baba classifications
      were fully explained to six orthopedic surgeons (three experts and three non
      experts), plain radiograms, CT imaging and implant information at the time of
      injury were presented, and the inter- and intra-observer reliability based on the
      Vancouver and Baba classifications and accuracy rates of stem stability were
      investigated. RESULTS: When interobserver reliability was made based on only
      radiograms, the mean kappa value of Baba classification-based judgments made by
      the experts was 0.76, and those of Vancouver classification-based judgments made
      by the experts was 0.41. When interobserver reliability was made based on the
      radiograms and CT images and implant information, the mean kappa value of Baba
      classification-based judgments made by the experts was 0.94, and those of
      Vancouver classification-based judgments were 0.48. Intra-observer reliability of
      Baba classification was 0.81 in the experts. Validity analysis showed 95.0%
      agreement within all subgroups. CONCLUSIONS: Reliability and validity of Baba
      classification was improved when additional information was given. We believe
      that this new classification is useful to establish a therapeutic strategy for
      femoral fractures around the stem.

PMID- 25603974
TI  - Association of TGFB1 29C/T and IL6 -572G/C polymorphisms with developmental hip
      dysplasia: a case-control study in adults with severe osteoarthritis.
AB  - PURPOSE: Developmental dysplasia of the hip (DDH) increases the risk of severe
      adult hip osteoarthritis (OA). Transforming growth factor-beta1 (TGF-beta1) and
      interleukin-6 (IL-6) are included in pathogenesis of OA, as well as in
      development of the musculoskeletal system. We investigated the association of
      single nucleotide polymorphisms (SNPs) known to reflect on the circulating levels
      of the two cytokines, specifically, 29 T -> C transition in the TGFB1 signal
      sequence (rs1800470) and -572G -> C transversion in the IL6 promoter (rs1800796),
      with DDH. METHODS: We conducted a case-control study in consecutive unrelated
      adults with severe hip OA scheduled for total hip arthroplasty. Cases, patients
      with OA secondary to DDH (n = 68) and controls, patients with OA unrelated to DDH
      (n = 152) were genotyped at the two loci. RESULTS: With adjustment for age, sex
      and genotype at the concurrent locus, cases were more likely (OR = 2.42, 95%CI
      1.08-5.43; p = 0.032) to be transition homozygous at TGFB1 locus 29, and also
      more likely (OR = 6.36, 95%CI 2.57-15.7; p < 0.001) to be transversion homozygous
      at IL6 locus -572 than controls. Cases were also more likely (OR = 11.3, 95%CI
      4.25-29.8; p < 0.001) than controls to carry one of the three genotypes combining
      transition/transversion homozygosity at both loci, or transition/transversion
      homozygosity at one and heterozygosity at the concurrent locus. CONCLUSIONS: Data
      suggest association between TGFB1 29 T -> C transition (rs1800470) and IL6 -572G 
      > C transversion (rs1800796) with DDH, and also a possibility of TGF-beta1 and IL
      6 interaction in DDH pathogenesis.

PMID- 25603975
TI  - Treatment effect of buparlisib, cetuximab and irradiation in wild-type or PI3KCA
      mutated head and neck cancer cell lines.
AB  - Introduction In complement to anti-EGFR therapy, the targeting of PI3K/AKT/mTOR
      signaling pathway is of particular interest in the management of Head and Neck
      Squamous Cell Carcinoma (HNSCC). Here, we assess the effects of PI3K inhibition
      combined with anti-EGFR monoclonal antibody cetuximab and/or irradiation (RT).
      Material and methods Anti-proliferative effects of the combination of buparlisib
      (a specific PI3K inhibitor), cetuximab and RT was determined in two HNSCC cell
      lines (CAL33, PI3KCA H1047R-mutated and CAL27, PI3KCA wild-type). We examined
      biochemical factors related to proliferation, apoptosis (caspases), DNA repair
      (ERCC1, XRCC1) and the PI3K pathway (pEGFR/EGFR, pAKT/AKT, p-p70, p4EBP1).
      Results The best synergistic combined treatment in inhibiting cell proliferation
      was sequence 2 (cetuximab followed by buparlisib) in both cell lines. Addition of
      RT increased sequence 2 anti-proliferative effect only in CAL27. Data on protein
      expression indicated a possible activation of mTORC2 complex and caspases
      proteins in CAL27 not seen in CAL33. In CAL33, the synergistic anti-proliferative
      effect of the two drugs may derive from the higher sensitivity of mutated cells
      to PI3K targeting. Conclusions Our study demonstrates a synergistic effect of
      cetuximab followed by buparlisib in both PI3KCA wild-type and mutated cells, even
      with different intracellular signaling cross-talk depending on mutational status.

PMID- 25603976
TI  - Remarkable clinical improvement with bilateral globus pallidus internus deep
      brain stimulation in a case of Lesch-Nyhan disease: five-year follow-up.
AB  - OBJECTIVES: Lesch-Nyhan disease (LND) is a hereditary disorder characterized by
      hyperuricemia, self-mutilation, developmental retardation, and movement disorders
      such as spasticity and dystonia. The lack of a precise understanding of the
      neurological dysfunction has precluded the development of useful conservative
      therapies. We present our experience treating a LND patient by bilateral globus
      pallidus internus (GPi) deep brain stimulation (DBS) with improvement in dystonia
      symptoms and disappearance of self-injurious behavior. METHODS: We present a 29
      year-old patient characterized by generalized severe dystonia and self-injurious
      behavior, both refractory to conservative treatment. The patient underwent a GPi
      bilateral electrode implant for chronic stimulation. Symptoms were evaluated with
      the Burke-Fhan-Marsden Dystonia Rating Scale (BFMDRS) and Mean Disability Scale
      (MDS) preoperatively and during the five-year follow-up. RESULTS: We observed a
      remarkable improvement in dystonia symptoms and complete disappearance of self
      injurious behavior. CONCLUSIONS: This case supports the hypothesis that
      automutilation in LND might be related to dysfunction of the basal ganglia
      circuits and the idea that bilateral GPi-DBS is a safe and effective treatment
      modality for this condition.

PMID- 25603977
TI  - Aspergillus flavus endocarditis of the native mitral valve in a bone marrow
      transplant patient.
AB  - BACKGROUND: Infective endocarditis due to Aspergillus species is an uncommon
      infection with a high mortality rate. It mostly occurs after the implantation of
      prosthetic heart valves. Parenteral nutrition, immunosuppression, broad-spectrum
      antibiotic regimens, and illegal intravenous drug use are the risk factors for
      developing infection. CASE REPORT: We report a case of Aspergillus flavus native
      mitral valve endocarditis in a patient who had allogeneic stem cell
      transplantation in the past due to myelodysplastic syndrome. CONCLUSIONS:
      Although it is rare and there is limited experience available with the diagnosis
      and treatment, early recognition and therapeutic intervention with systemic
      antifungal therapy and aggressive surgical intervention are critical to prevent
      further complications that may eventually lead to death. In addition, better
      novel diagnostic tools are needed to facilitate more accurate identification of
      patients with invasive Aspergillus and to permit earlier initiation of antifungal
      treatment.

PMID- 25603978
TI  - MicroRNA-21 controls hTERT via PTEN in human colorectal cancer cell
      proliferation.
AB  - Colorectal cancer is a major health problem worldwide. The aim of this study was
      to determine a role of microRNA-21 (miRNA-21) in colorectal cancer (CRC) and to
      elucidate miRNA-21 regulation of hTERT by phosphatase and tensin homologue
      (PTEN). Protein and mRNA samples were extracted with 30 CRC samples and one CRC
      cell lines. The expression of miRNA-21, hTERT, PTEN in CRC tissues and CRC cell
      lines was measured by real-time fluorescent quantitative PCR, Western blotting.
      Cell viability was detected by MTT and cell cycle assay. In this study, we show
      that the expression of miRNA-21 was overexpressed in CRC tissue and CRC cell
      lines compared with the control group. The effects of miRNA-21 were then assessed
      in MTT assays through in vitro transfection with a miRNA-21 mimic or inhibitor.
      PTEN has been identified as a target gene of miRNA-21 in CRC cell lines.
      Moreover, Western blot and qRT-PCR analyses revealed that miRNA-21 increased the
      expression of human telomerase reverse transcriptase (hTERT) via the PTEN/ERK1/2.
      In addition, Western blot analyses confirmed that an inverse correlation between
      PTEN and hTERT levels of high miRNA-21 RNA-expressing CRC tissues and cell lines.
      Finally, these data indicate that miRNA-21 regulates hTERT expression via the
      PTEN/ERK1/2 signaling pathway, therefore controlling CRC cell line growth. MiRNA
      21 may serve as a novel therapeutic target in CRC. 

PMID- 25603979
TI  - Changes in protein structure monitored by use of gas-phase hydrogen/deuterium
      exchange.
AB  - The study of protein conformation by solution-phase hydrogen/deuterium exchange
      (HDX) coupled to MS is well documented. This involves monitoring the exchange of
      backbone amide protons with deuterium and provides details concerning the
      protein's tertiary structure. However, undesired back-exchange during post-HDX
      analyses can be difficult to control. Here, gas-phase HDX-MS, during which labile
      hydrogens on amino acid side chains are exchanged in sub-millisecond time scales,
      has been employed to probe changes within protein structures. Addition of the
      solvent 2,2,2-trifluoroethanol to a protein in solution can affect the structure
      of the protein, resulting in an increase in secondary and/or tertiary structure
      which is detected using circular dichroism. Using a Synapt G2-S ESI-mass
      spectrometer modified to allow deuterated ammonia into the transfer ion guide
      (situated between the ion mobility cell and the TOF analyser), gas-phase HDX-MS
      is shown to reflect minor structural changes experienced by the proteins beta
      lactoglobulin and ubiquitin, as observed by the reduction in the level of
      deuterium incorporation. Additionally, the use of gas-phase HDX-MS to distinguish
      between co-populated proteins conformers within a solution is demonstrated with
      the disordered protein calmodulin; the gas-phase HDX-MS results correspond
      directly with complementary data obtained by use of ion mobility spectrometry-MS.

PMID- 25603980
TI  - Prevalence of Acinetobacter baumannii harboring ISAba1/bla OXA-23-like family in
      a burn center.
AB  - BACKGROUND: Refractory carbapenem resistant Acinetobacter baumannii (CRAB)
      isolates increase mortality and morbidity rates among patients with underlying
      disorders, especially in patients with burns. The aim of the current study was to
      understand the resistant determinants of CRAB isolates and their clonal
      relatedness collected from referral Burn center. METHODS: CRAB isolates were
      initially characterized and then antimicrobial susceptibility testing was
      assessed by E-test. Resistance determinants were investigated by PCR. Repetitive
      extragenic palindromic elements-PCR (REP-PCR) was used for clonality relatedness
      among isolates. RESULTS: Thirty CRAB isolates were collected during the study.
      Colistin was the most effective antibiotic, but, all of the isolates were
      resistant to carbapenems. intI1 was detected in two isolates and MBLs and gene
      cassettes were not detected. ISAba1, blaOXA-51, blaOXA-23 and ISAba1/blaOXA23
      like were detected in all, while blaOXA-24-like were present in 73% and blaOXA
      58&OXA-143 were not present in isolates. REP-PCR demonstrated three clusters,
      with the dominant B cluster, which contained 16 subgroups. CONCLUSION: CRAB
      harboring ISAba1/blaOXA-23-like family is widely disseminated in the studied Burn
      ward setting and the emergence of infection control measures should be regarded
      to limit refractory CRABs.

PMID- 25603982
TI  - Bosea vaviloviae sp. nov., a new species of slow-growing rhizobia isolated from
      nodules of the relict species Vavilovia formosa (Stev.) Fed.
AB  - The Gram-negative, rod-shaped slow-growing strains Vaf-17, Vaf-18(T) and Vaf-43
      were isolated from the nodules of Vavilovia formosa plants growing in the hard-to
      reach mountainous region of the North Ossetian State Natural Reserve (north
      Caucasus, Russian Federation). The sequencing of 16S rDNA (rrs), ITS region and
      five housekeeping genes (atpD, dnaK, recA, gyrB and rpoB) showed that the
      isolated strains were most closely related to the species Bosea lathyri (class
      Alphaproteobacteria, family Bradyrhizobiaceae) which was described for isolates
      from root nodules of Lathyrus latifolius. However the sequence similarity between
      the isolated strains and the type strain B. lathyri LMG 26379(T) for the ITS
      region was 90 % and for the housekeeping genes it was ranged from 92 to 95 %. All
      phylogenetic trees, except for the rrs-dendrogram showed that the isolates from
      V. formosa formed well-separated clusters within the Bosea group. Differences in
      phenotypic properties of the B. lathyri type strain and the isolates from V.
      formosa were studied using the microassay system GENIII MicroPlate BioLog. Whole
      cell fatty acid analysis showed that the strains Vaf-17, Vaf-18(T) and Vaf-43 had
      notable amounts of C16:0 (4.8-6.0 %), C16:0 3-OH (6.4-6.6 %), C16:1 omega5c (8.8
      9.0 %), C17:0 cyclo (13.5-13.9 %), C18:1 omega7c (43.4-45.4 %), C19:0 cyclo
      omega8c (10.5-12.6 %) and Summed Feature (SF) 3 (6.4-8.0 %). The DNA-DNA
      relatedness between the strains Vaf-18(T) and B. lathyri LMG 26379(T) was 24.0 %.
      On the basis of genotypic and phenotypic analysis a new species Bosea vaviloviae
      sp. nov. (type strain RCAM 02129(T) = LMG 28367(T) = Vaf-18(T)) is proposed. 

PMID- 25603981
TI  - Epidermal aquaporin-3 is increased in the cutaneous burn wound.
AB  - INTRODUCTION: Aquaporins (AQP) are a family of transmembrane proteins that
      transport water and small solutes such as glycerol across cell membranes. It is a
      mediator of transcellular water flow and plays an important role in maintaining
      intra/extracellular fluid homeostasis by facilitating water transport in response
      to changing osmotic gradients. In the skin, AQPs permit rapid, regulated, and
      selective water permeability and have been demonstrated to play a role in skin
      hydration, cell proliferation, migration, immunity, and wound healing. However,
      the expression of AQP-3 in the cutaneous burn wound has never been elucidated. We
      sought to assess the expression of AQP-3 in patients with burn wounds. METHODS: A
      fresh full thickness biopsy sample was taken from the center of the burn wound,
      the burn wound edge, and the graft donor site in 7 patients (n=21), approximately
      3-7 days post injury. Fixed, paraffin embedded sections were stained using AQP-3
      specific antibody and examined by immunofluorescence. Fresh samples were
      processed to quantify AQP-3 protein expression with Western blot analysis.
      RESULTS: The central portion of the burn wound revealed destruction of the
      epidermis and dermis with no AQP-3 present. Along the burn wound edge where the
      epidermal architecture was disrupted, there was robust AQP-3 staining. Western
      blot analysis demonstrated deeper staining along the burn wound edge compared to
      unburned skin (control). Quantification of the protein shows a significant amount
      of AQP-3 expression along the burn wound edge (3.6+/-0.34) compared to unburned
      skin (2.1+/-0.28, N=7, *p<0.05). There is no AQP-3 expression in the burn wound
      center. CONCLUSION: AQP-3 expression is increased in the burn wound following
      injury. While its role in wound healing has been defined, we report for the first
      time the effect of cutaneous burns on AQP-3 expression. Our data provides the
      first step in determining its functional role in burn wounds. We hypothesize that
      development of AQP3 targeted therapies may improve burn wound healing.

PMID- 25603984
TI  - Contextual correlates of intensity of smoking in northeast India.
AB  - OBJECTIVES: This study assessed the significance of socio-demographic and
      contextual factors on the number of daily cigarette and bidi smoking in northeast
      India. METHODS: This study is based on the data from the Global Adult Tobacco
      Survey-India (2009-2010). Community asset is measured as the totality of all
      households' durables and community affinity to smoking as the proportion of
      households which allowed smoking in the house. RESULTS: High daily cigarette and
      bidi smokers constitute 20 and 30 % of the respective smokers and they smoke 35.8
      cigarettes and 14.6 bidis daily, respectively, on the average. The higher is the
      community affinity to smoking, the higher is the intensity of smoking among the
      high daily cigarette smokers. Advancing age and educational attainment have
      significant deterrent effect on the intensity of cigarette and bidi smoking.
      CONCLUSIONS: Contextual factors are found to be important for regional tobacco
      control programmes. The need for reaching out to communities and the importance
      of promotion of public-private partnership under the provision of corporate
      social responsibility for effectiveness of tobacco control programme is
      recommended.

PMID- 25603983
TI  - Understanding children: a qualitative study on health assets of the Internet in
      Spain.
AB  - OBJECTIVES: This research was designed to explore the opinions held by primary
      school pupils about the Internet as a source of assets for health and well-being.
      METHODS: A qualitative study was carried out based on 8 focus groups comprising
      64 pupils from 8 primary schools in Spain. RESULTS: Our findings describe the
      Internet as a tool for learning, communication, fun and health care. In addition,
      they reveal how children understand influences on health and well-being in
      relation to their view of the Internet. The results are discussed in terms of the
      public-health implications of digital literacy, as well as its connection to well
      being, especially in relation to health assets. CONCLUSIONS: The Internet is an
      important resource for children's health and well-being, which, through learning,
      communication, fun and health care, encourages them to make use of it. Digital
      and health literacy constitutes the foundation required for browsing the Internet
      in a positive way, as identified by the children interviewed in this study, and
      especially in relation to the health assets that the Internet can contain.

PMID- 25603985
TI  - Long-term dynamics in physical activity behaviour across the transition to
      parenthood.
AB  - OBJECTIVES: Gaining a deeper understanding of the dynamic relationships between
      the transition to parenthood and moderate-to-vigorous physical activity (MVPA)
      amongst men and women in Australia. METHODS: 12 years of nationally
      representative panel data from the Household, Income and Labour Dynamics in
      Australia Survey and a piecewise pre/post fixed-effect modelling strategy that
      controls for person-specific unobserved effects and allows for non-linear
      associations are used. RESULTS: Both men and women decrease the frequency of MVPA
      in the years preceding the birth of their first child. An abrupt fall amongst men
      and a smooth, non-linear decreasing trend amongst women are apparent in the post
      birth years. Neither men nor women recover their pre-birth MVPA frequency in
      subsequent years. CONCLUSIONS: Parenthood is an important factor influencing
      MVPA, with more marked impacts on women's than men's behaviour. Policymakers
      interested in promoting MVPA should focus on parenthood as a critical deterring
      factor that can trigger long-term trends of low MVPA. The proposed model can be
      expanded to explore the influence on MVPA of other life-course transitions.

PMID- 25603986
TI  - Detection and quantification of 4(5)-methylimidazole in cooked meat.
AB  - 4(5)-Methylimidazole (4-MeI) is a nitrogen-containing heterocyclic compound found
      in class III and IV ammoniated caramel colors, a group of additives widely used
      in the food industry. A suspected carcinogen and neurotoxin and efforts are
      underway to limit its presence in foods. Several methods have been developed to
      detect and quantitate 4-MeI in different food matrices, including roasted coffee,
      beer, soft drinks, and soy sauce; however, no methods are available to measure 4
      MeI in cooked meat and meat products containing lipids and high levels of
      interfering nitrogen compounds, such as amino acids and peptides. A rapid method
      using 0.1 M sodium acetate buffer (pH 5) as an extraction solvent followed by
      derivatization with isobutylchloroformate and gas chromatograph mass-spectrometry
      was developed to quantify 4-MeI in cooked meat products with added caramel colors
      containing 4-MeI. Selected ion monitoring mode was used to monitor 4-MeI ions
      fragments. In the 8 commercial meat products tested, 4-MeI levels ranged from
      0.041 to 1.015 mg/kg, with recovery of 94.76% to 103.94%. In addition, a matrix
      matched calibration performed by analyzing a spiked cooked meat sample indicated
      no significant difference (P > 0.05), which means the meat matrix had no effect
      on the developed method. This method proved useful in analyzing 4-MeI in meat
      products with added caramel color containing 4-MeI. 

PMID- 25603987
TI  - Continual stenting of ileal stricture after restorative proctocolectomy with
      ileostoma in a pregnant woman.

PMID- 25603989
TI  - The aflatoxin-detoxifizyme specific expression in mouse parotid gland.
AB  - The aflatoxin-detoxifizyme (ADTZ) gene derived from Armillariella tabescens was
      cloned into parotid gland-specific expression vector (pPSPBGPneo) to construct
      the parotid gland-specific vector expressing ADTZ (pPSPBGPneo-ADTZ). Transgenic
      mice were generated by microinjection and identified by using PCR and Southern
      blotting analysis. PCR and Southern blotting analysis showed that total six
      transgenic mice carried the ADTZ gene were generated. RT-PCR analysis indicated
      that the expression of ADTZ mRNA could be detected only in parotid glands of the
      transgenic mice. The ADTZ activity in the saliva was found to be 3.72 +/- 1.64
      U/mL. After feeding a diet containing aflatoxin B1 (AFB1) for 14 days, the effect
      of ADTZ on serum biochemical indexes and AFB1 residues in serum and liver of mice
      were evaluated. The results showed that total protein and globulin contents in
      the test treatment (transgenic mice) produced ADTZ were significantly higher than
      that of the positive control, while alanine aminotransferase and aspartate
      aminotransferase activity in serum of the test treatment (transgenic mice) were
      remarkably lower compared to that of the positive control (P < 0.05). Moreover,
      AFB1 residues in serum and liver of the test treatment (transgenic mice) were
      significantly lower compared with that of the positive control (P < 0.05). These
      results in the study confirmed that ADTZ produced in transgenic mice could
      reduce, even eliminate the negative effects of AFB1 on mice.

PMID- 25603988
TI  - Molecular scissors and their application in genetically modified farm animals.
AB  - Molecular scissors (MS), incl. Zinc Finger Nucleases (ZFN), Transcription
      activator like endoncleases (TALENS) and meganucleases possess long recognition
      sites and are thus capable of cutting DNA in a very specific manner. These
      molecular scissors mediate targeted genetic alterations by enhancing the DNA
      mutation rate via induction of double-strand breaks at a predetermined genomic
      site. Compared to conventional homologous recombination based gene targeting, MS
      can increase the targeting rate 10,000-fold, and gene disruption via mutagenic
      DNA repair is stimulated at a similar frequency. The successful application of
      different MS has been shown in different organisms, including insects,
      amphibians, plants, nematodes, and mammals, including humans. Recently, another
      novel class of molecular scissors was described that uses RNAs to target a
      specific genomic site. The CRISPR/Cas9 system is capable of targeting even
      multiple genomic sites in one shot and thus could be superior to ZFNs or TALEN,
      especially by its easy design. MS can be successfully employed for improving the
      understanding of complex physiological systems, producing transgenic animals,
      incl. creating large animal models for human diseases, creating specific cell
      lines, and plants, and even for treating human genetic diseases. This review
      provides an update on molecular scissors, their underlying mechanism and focuses
      on new opportunities for generating genetically modified farm animals. 

PMID- 25603990
TI  - Toll-like receptor 4 mediates the regenerative effects of bone grafts for
      calvarial bone repair.
AB  - Craniofacial trauma is difficult to repair and presents a significant burden to
      the healthcare system. The inflammatory response following bone trauma is
      critical to initiate healing, serving to recruit inflammatory and progenitor
      cells and to promote angiogenesis. A role for inflammation in graft-induced bone
      regeneration has been suggested, but is still not well understood. The current
      study assessed the impact of Toll-like receptor (TLR4) signaling on calvarial
      repair in the presence of morselized bone components. Calvarial defects in wild
      type and global TLR4(-/-) knockout mouse strains were treated with fractionated
      bone components in the presence or absence of a TLR4 neutralizing peptide. Defect
      healing was subsequently evaluated over 28 days by microcomputed tomography and
      histology. The matrix-enriched fraction of morselized bone stimulated calvarial
      bone repair comparably with intact bone graft, although the capacity for grafts
      to induce calvarial bone repair was significantly diminished by inhibition or
      genetic ablation of TLR4. Overall, our findings suggest that the matrix component
      of bone graft stimulates calvarial bone repair in a TLR4-dependent manner. These
      results support the need to better understand the role of inflammation in the
      design and implementation of strategies to improve bone healing. 

PMID- 25603991
TI  - Leghemoglobin is nitrated in functional legume nodules in a tyrosine residue
      within the heme cavity by a nitrite/peroxide-dependent mechanism.
AB  - Protein tyrosine (Tyr) nitration is a post-translational modification yielding 3
      nitrotyrosine (NO2 -Tyr). Formation of NO2 -Tyr is generally considered as a
      marker of nitro-oxidative stress and is involved in some human pathophysiological
      disorders, but has been poorly studied in plants. Leghemoglobin (Lb) is an
      abundant hemeprotein of legume nodules that plays an essential role as an O2
      transporter. Liquid chromatography coupled to tandem mass spectrometry was used
      for a targeted search and quantification of NO2 -Tyr in Lb. For all Lbs examined,
      Tyr30, located in the distal heme pocket, is the major target of nitration. Lower
      amounts were found for NO2 -Tyr25 and NO2 -Tyr133. Nitrated Lb and other as yet
      unidentified nitrated proteins were also detected in nodules of plants not
      receiving NO3- and were found to decrease during senescence. This demonstrates
      formation of nitric oxide (NO) and NO2- by alternative means to nitrate
      reductase, probably via a NO synthase-like enzyme, and strongly suggests that
      nitrated proteins perform biological functions and are not merely metabolic
      byproducts. In vitro assays with purified Lb revealed that Tyr nitration requires
      NO2- + H2 O2 and that peroxynitrite is not an efficient inducer of nitration,
      probably because Lb isomerizes it to NO3-. Nitrated Lb is formed via oxoferryl
      Lb, which generates nitrogen dioxide and tyrosyl radicals. This mechanism is
      distinctly different from that involved in heme nitration. Formation of NO2 -Tyr
      in Lb is a consequence of active metabolism in functional nodules, where Lb may
      act as a sink of toxic peroxynitrite and may play a protective role in the
      symbiosis. 

PMID- 25603993
TI  - [Assessment I: from the beginnings of the challenges to aspects of future
      development].

PMID- 25603992
TI  - Low penetrance in facioscapulohumeral muscular dystrophy type 1 with large
      pathological D4Z4 alleles: a cross-sectional multicenter study.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy type 1(FSHD1) is an autosomal
      dominant disorder associated with the contraction of D4Z4 less than 11 repeat
      units (RUs) on chromosome 4q35. Penetrance in the range of the largest alleles is
      poorly known. Our objective was to study the penetrance of FSHD1 in patients
      carrying alleles ranging between 6 to10 RUs and to evaluate the influence of sex,
      age, and several environmental factors on clinical expression of the disease.
      METHODS: A cross-sectional multicenter study was conducted in six French and one
      Swiss neuromuscular centers. 65 FSHD1 affected patients carrying a 4qA allele of
      6-10 RUs were identified as index cases (IC) and their 119 at-risk relatives were
      included. The age of onset was recorded for IC only. Medical history,
      neurological examination and manual muscle testing were performed for each
      subject. Genetic testing determined the allele size (number of RUs) and the
      4qA/4qB allelic variant. The clinical status of relatives was established blindly
      to their genetic testing results. The main outcome was the penetrance defined as
      the ratio between the number of clinically affected carriers and the total number
      of carriers. RESULTS: Among the relatives, 59 carried the D4Z4 contraction. At
      the clinical level, 34 relatives carriers were clinically affected and 25
      unaffected. Therefore, the calculated penetrance was 57% in the range of 6-10
      RUs. Penetrance was estimated at 62% in the range of 6-8 RUs, and at 47% in the
      range of 9-10 RUs. Moreover, penetrance was lower in women than men. There was no
      effect of drugs, anesthesia, surgery or traumatisms on the penetrance.
      CONCLUSIONS: Penetrance of FSHD1 is low for largest alleles in the range of 9-10
      RUs, and lower in women than men. This is of crucial importance for genetic
      counseling and clinical management of patients and families.

PMID- 25603995
TI  - Prostate cancer organoids: a potential new tool for testing drug sensitivity.
AB  - Recent technical advances have enabled for the first time, reliable in vitro
      culture of prostate cancer samples as prostate cancer organoids. This
      breakthrough provides the significant possibility of high throughput drug
      screening covering the spectrum of prostate cancer phenotypes seen clinically.
      These advances will enable precision medicine to become a reality, allowing
      patient samples to be screened for effective therapeutics ex vivo, with tailoring
      of treatments specific to that individual. This will hopefully lead to enhanced
      clinical outcomes, avoid morbidity due to ineffective therapies and improve the
      quality of life in men with advanced prostate cancer. 

PMID- 25603994
TI  - A "green" strategy to construct non-covalent, stable and bioactive coatings on
      porous MOF nanoparticles.
AB  - Nanoparticles made of metal-organic frameworks (nanoMOFs) attract a growing
      interest in gas storage, separation, catalysis, sensing and more recently,
      biomedicine. Achieving stable, versatile coatings on highly porous nanoMOFs
      without altering their ability to adsorb molecules of interest represents today a
      major challenge. Here we bring the proof of concept that the outer surface of
      porous nanoMOFs can be specifically functionalized in a rapid, biofriendly and
      non-covalent manner, leading to stable and versatile coatings. Cyclodextrin
      molecules bearing strong iron complexing groups (phosphates) were firmly anchored
      to the nanoMOFs' surface, within only a few minutes, simply by incubation with
      aqueous nanoMOF suspensions. The coating procedure did not affect the nanoMOF
      porosity, crystallinity, adsorption and release abilities. The stable
      cyclodextrin-based coating was further functionalized with: i) targeting moieties
      to increase the nanoMOF interaction with specific receptors and ii) poly(ethylene
      glycol) chains to escape the immune system. These results pave the way towards
      the design of surface-engineered nanoMOFs of interest for applications in the
      field of targeted drug delivery, catalysis, separation and sensing. 

PMID- 25603996
TI  - Bacillus dabaoshanensis sp. nov., a Cr(VI)-tolerant bacterium isolated from heavy
      metal-contaminated soil.
AB  - A Cr(VI)-tolerant, Gram-staining-positive, rod-shaped, endospore-forming and
      facultative anaerobic bacterium, designated as GSS04(T), was isolated from a
      heavy-metal-contaminated soil. Strain GSS04(T) was Cr(VI)-tolerant with a minimum
      inhibitory concentration of 600 mg l(-1) and was capable of reducing Cr(VI) under
      both aerobic and anaerobic conditions. Growth occurred with presence of 0-3 %
      (w/v) NaCl (optimum 1 %), at pH 5.5-10.0 (optimum pH 7.0) and 15-50  degrees C
      (optimum 30-37  degrees C). The main respiratory quinone was MK-7 and the major
      fatty acids were anteiso-C15:0 and iso-C15:0. The DNA G+C content was 41.1 mol%.
      The predominant polar lipid was diphosphatidylglycerol. Based on 16S rRNA gene
      sequence similarity, the closest phylogenetic relative was Bacillus shackletonii
      DSM 18868(T) (97.6 %). The DNA-DNA hybridization between GSS04(T) and its closest
      relatives revealed low relatedness (<70 %). The results of phenotypic,
      chemotaxonomic and genotypic analyses clearly indicated that strain GSS04(T)
      represents a novel species of the genus Bacillus, for which the name Bacillus
      dabaoshanensis sp. nov. is proposed. The type strain is GSS04(T) (=CCTCC AB
      2013260(T) = KCTC 33191(T)). 

PMID- 25603998
TI  - Memory efficient assembly of human genome.
AB  - The ability to detect the genetic variations between two individuals is an
      essential component for genetic studies. In these studies, obtaining the genome
      sequence of both individuals is the first step toward variation detection
      problem. The emergence of high-throughput sequencing (HTS) technology has made
      DNA sequencing practical, and is widely used by diagnosticians to increase their
      knowledge about the casual factor in genetic related diseases. As HTS advances,
      more data are generated every day than the amount that scientists can process.
      Genome assembly is one of the existing methods to tackle the variation detection
      problem. The de Bruijn graph formulation of the assembly problem is widely used
      in the field. Furthermore, it is the only method which can assemble any genome in
      linear time. However, it requires an enormous amount of memory in order to
      assemble any mammalian size genome. The high demands of sequencing more
      individuals and the urge to assemble them are the driving forces for a memory
      efficient assembler. In this work, we propose a novel method which builds the de
      Bruijn graph while consuming lower memory. Moreover, our proposed method can
      reduce the memory usage by 37% compared to the existing methods. In addition, we
      used a real data set (chromosome 17 of A/J strain) to illustrate the performance
      of our method. 

PMID- 25603997
TI  - Identification of a Prg4-expressing articular cartilage progenitor cell
      population in mice.
AB  - OBJECTIVE: To generate knockin mice that express a tamoxifen-inducible Cre
      recombinase from the Prg4 locus (Prg4(GFPCreERt2) mice) and to use these animals
      to fate-map the progeny of Prg4-positive articular cartilage cells at various
      ages. METHODS: We crossed Prg4(GFPCreERt2) mice with Rosa26(floxlacZ) or
      Rosa26(mTmG) reporter strains, admin-istered tamoxifen to the double heterozygous
      offspring at different ages, and assayed Cre-mediated recom-bination by
      histochemistry and/or fluorescence microscopy. RESULTS: In 1-month-old mice, the
      expression of the Prg4(GFPCreERt2) allele mirrored the expression of endogenous
      Prg4 and, when tamoxifen was admin-istered for 10 days, caused Cre-mediated
      recombination in ~70% of the superficial-most chondrocytes. Prg4(GFPCreERt2)
      expressing cells were mostly confined to the top 3 cell layers of the articular
      cartilage in 1-month-old mice, but descendants of these cells were located in
      deeper regions of the articular cartilage in aged mice. On embryonic day 17.5,
      Prg4(GFPCreERt2)-expressing cells were largely restricted to the superficial-most
      cell layer of the forming joint, yet at ~1 year, the progeny of these cells
      spanned the depth of the articular cartilage. CONCLUSION: Our results suggest
      that Prg4-expressing cells located at the joint surface in the embryo serve as a
      progenitor population for all deeper layers of the mature articular cartilage.
      Also, our findings indicate that Prg4(GFPCreERt2) is expressed by superficial
      chondrocytes in young mice, but expands into deeper regions of the articular
      cartilage as the animals age. The Prg4(GFPCreERt2) allele should be a useful tool
      for inducing efficient Cre-mediated recombination of loxP-flanked alleles at
      sites of Prg4 expression.

PMID- 25603999
TI  - Supervised self-administration of outpatient parenteral antibiotic  therapy: a
      report from a large tertiary hospital in Australia.
AB  - INTRODUCTION: Outpatient parenteral antibiotic therapy (OPAT) has become
      established as a standard of care in most Australian hospitals to treat a variety
      of infections. Since 1998, the Alternate Site Infusion Service (ASIS) has
      provided an OPAT service to five hospitals in southern Brisbane, Queensland,
      using predominantly a patient or carer administration model (self-administered, S
      OPAT). The aim of this study was to evaluate outcomes of our S-OPAT programme.
      METHODS: Consecutive patients treated by ASIS at the Princess Alexandra Hospital
      from January 1, 2011 to December 31, 2011 were reviewed. Data on patient
      demographics, diagnoses, microbiology, antimicrobial therapy, duration, outcome,
      and complications were sourced from a prospectively collected database and from
      patient medical records. RESULTS: There were 150 episodes involving 144 patients
      resulting in 3520 days of OPAT; the median duration on the programme was 22 days
      (range 4-106 days). Patient or carer administration occurred in the majority of
      episodes. The most common indication by far was bone or joint infection (47% of
      patients), followed by infective endocarditis (9%). Staphylococcus aureus was the
      most frequently treated organism. The overall cure rate was 93%. On multivariate
      analysis, patients with two or more comorbidities had an increased risk of
      failure. Line-related complications occurred in 1.4/1000 catheter-days. Rash was
      the most common drug-related event. Despite the extensive use of broad-spectrum
      antibiotics there were no cases of Clostridium difficile infection during therapy
      and for up to 28 days post cessation of intravenous antibiotics. The cost of OPAT
      per patient excluding drug administration and home visits was approximately A$
      150.00/day, significantly lower than the cost of an inpatient bed, which is
      estimated to be A$ 500-800/day.5 CONCLUSION: OPAT using a patient or carer
      administration model is an effective and safe option for the management of
      selected patients with infection requiring intravenous antibiotics.

PMID- 25604000
TI  - Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity
      Disorder: Searching for Distinctive/Common Clinical Features.
AB  - Recent studies support several overlapping traits between autism spectrum
      disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the
      existence of a combined phenotype. The aim of our study was to evaluate the
      common or distinctive clinical features between ASD and ADHD in order to identify
      possible different phenotypes that could have a clinical value. We enrolled 181
      subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD
      group (that met diagnostic criteria for both ASD and ADHD), and control group.
      Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD
      symptoms, and adaptive behaviors were investigated through the following test:
      Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of
      Intelligence or Leiter International Performances Scale Revised, Child Behavior
      Checklist, Conners' Rating Scales-Revised, SNAP-IV Rating Scale, the Social
      Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD
      group differs from ADHD or ASD in some domains such as lower IQ mean level and a
      higher autistic symptoms severity. However, the ASD+ADHD group shares inattention
      and hyperactivity deficit and some emotional and behavior problems with the ADHD
      group, while it shares adaptive behavior impairment with ASD group. These
      findings provide a new understanding of clinical manifestation of ASD+ADHD
      phenotype, they may also inform a novel treatment target.

PMID- 25604002
TI  - Acute and chronic humeral shaft fractures in adults.
AB  - Humeral shaft fractures account for up to 5% of all fractures. Many of these
      fractures are still being treated conservatively using functional (Sarmiento)
      bracing or a hanging arm cast. Union is achieved in 10 weeks in more than 94% of
      cases. Angulation of less than 30 degrees  varus or valgus and less than 20
      degrees  flessum or recurvatum can be tolerated by the patient from a functional
      and esthetic point of view. The ideal candidate for this treatment is a patient
      with an isolated fracture. Plate and screw fixation of the fracture results in
      union in 11 to 19 weeks. Reported complications include non-union (2.8-21%),
      secondary radial nerve palsy (6.5-12%) and infection (0.8-2.4%). Anterograde or
      retrograde locked intramedullary nailing requires knowledge of nailing techniques
      and regional anatomy to avoid the complications associated with the technique.
      Union is obtained in 10-15 weeks. Reported complications consist of non-union (2
      17.4%), infection (0-4%) and secondary radial nerve palsy (2.7-5%). Hackethal
      bundle nailing is still used for fracture fixation, despite an elevated
      complication rate (5-24% non-union and 6-29% pin migration) because of its low
      cost and simple instrumentation. Union is achieved in 8-9 weeks. Controversy
      remains about the course to follow when the radial nerve is injured initially. If
      the fracture is open, significantly displaced, associated with a vascular injury
      or requires surgical treatment, the nerve must be explored. In other cases, the
      recommended approach varies greatly. Conservative treatment is inexpensive and
      has a low complication rate. Humeral shaft fractures are increasingly being
      treated surgically, at a greater cost and higher risk of complications.

PMID- 25604001
TI  - Atrial fibrillation and cycling: six year follow-up of the Taupo bicycle study.
AB  - BACKGROUND: Atrial Fibrillation (AF) is the most common sustained cardiac
      arrhythmia, and the incidence of AF is increased markedly among elite athletes.
      It is not clear how lesser levels of physical activity in the general population
      influence AF. We asked whether participation in the Taupo Cycle Challenge was
      associated with increased hospital admissions due to AF, and within the cohort,
      whether admissions for AF were related to frequency and intensity of cycling.
      METHODS: Participants in the 2006 Lake Taupo Cycle Challenge, New Zealand's
      largest mass cycling event, were invited to complete an on-line questionnaire.
      Those who agreed (n = 2590, response rate = 43.1%) were followed up by record
      linkage via the National Minimum Health Database from December 1 2006 until June
      30 2013, to identify admissions to hospital due to AF. RESULTS: The age and
      gender standardized admission rate for AF was similar in the Taupo cohort (19.60
      per 10,000 per year) and the national population over the same period (2006-2011)
      (19.45 per 10,000 per year). Within the study cohort (men only), for every
      additional hour spent cycling per week the risk changed by 0.90 (95% confidence
      interval 0.79 - 1.01). This result did not change appreciably after adjustment
      for age and height. CONCLUSIONS: Hospital admission due to AF was not increased
      above the national rate in this group of non-elite cyclists, and within the group
      the rate of AF did not increase with amount of cycling. The level of activity
      undertaken by this cohort of cyclists was, on average, not sufficient to increase
      the risk of hospitalization for AF.

PMID- 25604003
TI  - How do you circumcise a nation? The Rwandan case study.
AB  - Voluntary medical male circumcision has been conclusively demonstrated to reduce
      the lifetime risk of male acquisition of HIV. The strategy has been adopted as a
      component of a comprehensive strategy towards achieving an AIDS-free generation.
      A number of countries in which prevalence of HIV is high and circumcision is low
      have been identified as a priority, where innovative approaches to scale-up are
      currently being explored. Rwanda, as one of the priority countries, has faced a
      number of challenges to successful scale-up. We discuss here how simplifications
      in the procedure, addressing a lack of healthcare infrastructure and mobilizing
      resources, and engaging communities of both men and women have permitted Rwanda
      to move forward with more optimism in its scale-up tactics. Examples from Rwanda
      are used to highlight how these barriers can and should be addressed. 

PMID- 25604004
TI  - Analysis of thiabendazole, 4-tert-octylphenol and chlorpyrifos in waste and
      sewage water by direct injection - micellar liquid chromatography.
AB  - A micellar liquid chromatographic method has been developed for the simultaneous
      quantification of the pesticides thiabendazole and chlorpyrifos, as well as an
      alkylphenol, which is included in pesticide formulations, i.e., 4-tert
      octylphenol, in water. A sample was filtered and directly injected, avoiding
      large extraction steps using toxic solvents, thus expediting the experimental
      procedure. The contaminants were eluted without interferences in <17 min, using a
      mobile phase of 0.15 M sodium dodecyl sulfate - 6% 1-pentanol buffered at pH 3,
      running through a C18 column at 1 mL min(-1) under the isocratic mode. This
      optimal mobile phase was selected using a statistical approach, which considers
      the retention factor, efficiency and peak shape of the analytes measured in only
      a few mobile phases. The detection was carried out by measuring absorbance at 220
      nm. The method was successfully validated in terms of specificity, calibration
      range (0.5-10 mg L(-1)), linearity (r(2) > 0.994), limit of detection and
      quantification (0.2-0.3; and 0.5-0.8 mg L(-1), respectively), intra- and interday
      accuracy (95.2-102.9%), precision (<8.3%), and ruggedness (<9.3%). The stability
      in storage conditions (at least 14 days) was studied. The method was safe,
      inexpensive, produced little pollutant and has a short analysis time, thus it is
      useful for the routine analysis of samples. Finally, the method was applied to
      analyse wastewater from the fruit-processing industry, wastewater treatment
      plants, and in sewage water belonging to the Castello area (Spain). The results
      were similar to those obtained by an already reliable method.

PMID- 25604005
TI  - Cancer risk in patients with type 2 diabetes mellitus and their relatives.
AB  - Epidemiological studies indicate that risks of certain cancers are increased in
      individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be
      representative of the entire population of T2DM patients as most of them are
      treated in primary health cares. To examine the subsequent cancer risk in
      individuals with T2DM from hospitals and primary health cares, and in their
      siblings and spouses, standardized incidence ratios (SIRs) were used to assess
      systematically risks of 35 cancer sites/types in individuals with T2DM using a
      nationwide Swedish database covering the period 1964 through 2010. Increased SIRs
      were recorded for 24 cancer sites/types in individuals with T2DM. The highest
      SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A
      decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs
      during the whole follow-up period: colon, liver, pancreatic, endometrial and
      kidney cancers. T2DM patients in inpatient, outpatient and primary health care
      showed similar risk patterns. The overall SIRs for cancer in the siblings and
      spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin
      users showed an overall increased risk of cancer. This study showed increased
      risks of 24 cancers in individuals with T2DM, but not in their siblings or
      spouses, suggesting that the profound metabolic disturbances of the underlying
      disease may explain the observed increases. Further studies examining the
      endogenous and exogenous factors underlying these associations are needed. 

PMID- 25604006
TI  - Chip-based free-flow electrophoresis with integrated nanospray mass-spectrometry.
AB  - Free-flow electrophoresis is an ideal tool for preparative separations in
      continuous microflow. With the approach presented herein for coupling free-flow
      electrophoresis and mass spectrometry it is now also possible to trace non
      fluorescent compounds and identify them by means of mass spectrometry. The
      functionality of the method and its potential as an integrated separation unit
      for microflow synthesis is demonstrated by application to a multicomponent [3+2]
      cycloannulation. 

PMID- 25604011
TI  - Local antibiotic delivery systems in diabetic foot osteomyelitis: time for one
      step beyond?
AB  - In patients with diabetes mellitus, osteomyelitis is a severe, difficult-to-treat
      form of foot infection. In the management of diabetic foot osteomyelitis,
      carriers for local delivery of antimicrobial agents have begun to be tried, in an
      attempt to provide high local antibiotic concentrations. Randomized clinical
      trials are now expected to clarify when this new approach should be used and how
      it can be integrated into the overall therapeutic strategy for diabetic foot
      osteomyelitis. 

PMID- 25604012
TI  - Global analysis of gene expression profiles in physic nut (Jatropha curcas L.)
      seedlings exposed to drought stress.
AB  - BACKGROUND: Physic nut (Jatropha curcas L.) is a small perennial tree or large
      shrub, which is well-adapted to semi-arid regions and is considered to have
      potential as a crop for biofuel production. It is now regarded as an excellent
      model for studying biofuel plants. However, our knowledge about the molecular
      responses of this species to drought stress is currently limited. RESULTS: In
      this study, genome-wide transcriptional profiles of roots and leaves of 8-week
      old physic nut seedlings were analyzed 1, 4 and 7 days after withholding
      irrigation. We observed a total of 1533 and 2900 differentially expressed genes
      (DEGs) in roots and leaves, respectively. Gene Ontology analysis showed that the
      biological processes enriched in droughted plants relative to unstressed plants
      were related to biosynthesis, transport, nucleobase-containing compounds, and
      cellular protein modification. The genes found to be up-regulated in roots were
      related to abscisic acid (ABA) synthesis and ABA signal transduction, and to the
      synthesis of raffinose. Genes related to ABA signal transduction, and to
      trehalose and raffinose synthesis, were up-regulated in leaves. Endoplasmic
      reticulum (ER) stress response genes were significantly up-regulated in leaves
      under drought stress, while a number of genes related to wax biosynthesis were
      also up-regulated in leaves. Genes related to unsaturated fatty acid biosynthesis
      were down-regulated and polyunsaturated fatty acids were significantly reduced in
      leaves 7 days after withholding irrigation. As drought stress increased, genes
      related to ethylene synthesis, ethylene signal transduction and chlorophyll
      degradation were up-regulated, and the chlorophyll content of leaves was
      significantly reduced by 7 days after withholding irrigation. CONCLUSIONS: This
      study provides us with new insights to increase our understanding of the response
      mechanisms deployed by physic nut seedlings under drought stress. The genes and
      pathways identified in this study also provide much information of potential
      value for germplasm improvement and breeding for drought resistance.

PMID- 25604013
TI  - Generation and characterization of an endothelin-2 iCre mouse.
AB  - A novel transgenic mouse line that expresses codon-improved Cre recombinase
      (iCre) under regulation of the Endothelin-2 gene (edn2) promoter was developed
      for the conditional deletion of genes in Endothelin-2 lineage cells and for the
      spatial and temporal localization of Endothelin-2 expression. Endothelin-2 (EDN2,
      ET-2, previously VIC) is a transcriptionally regulated 21 amino acid peptide
      implicated in vascular homeostasis, and more recently in female reproduction,
      gastrointestinal function, immunology, and cancer pathogenesis that acts through
      membrane receptors and G-protein signaling. A cassette (edn2-iCre) was
      constructed that contained iCre, a polyadenylation sequence, and a neomycin
      selection marker in front of the endogenous start codon of the edn2 gene in a
      mouse genome BAC clone. The cassette was introduced into the C57BL/6 genome by
      pronuclear injection, and two lines of edn2-iCre positive mice were produced. The
      edn2-iCre mice were bred with ROSA26-lacZ and Ai9 reporter mice to visualize
      areas of functional iCre expression. Strong expression was seen in the
      periovulatory ovary, stomach and small intestine, and colon. Uniquely, we report
      punctate expression in the corneal epithelium, the liver, the lung, the
      pituitary, the uterus, and the heart. In the embryo, expression is localized in
      developing hair follicles and the dermis. Therefore, edn2-iCre mice will serve as
      a novel line for conditional gene deletion in these tissues.

PMID- 25604015
TI  - Abstracts of the 4th Annual Meeting, Frontiers in Neurology, November 21, 2014,
      Dublin, Ireland.

PMID- 25604014
TI  - Comparison of oncology drug approval between Health Canada and the US Food and
      Drug Administration.
AB  - BACKGROUND: The drug approval timeline is a lengthy process that often varies
      between countries. The objective of this study was to delineate the Canadian drug
      approval timeline for oncology drugs and to compare the time to drug approval
      between Health Canada (HC) and the US Food and Drug Administration (FDA).
      METHODS: In total, 54 antineoplastic drugs that were approved by the FDA between
      1989 and 2012 were reviewed. For each drug, the following milestones were
      determined: the dates of submission and approval for both the FDA and HC and the
      dates of availability on provincial drug formularies in Canadian provinces and
      territories. The time intervals between the aforementioned milestones were
      calculated. RESULTS: Of 54 FDA-approved drugs, 49 drugs were approved by HC at
      the time of the current study. The median time from submission to approval was 9
      months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR,
      10-21.1 months) for HC (P < .0006). The time from HC approval to the placement of
      a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2
      months), and there was no interprovincial variability among the 5 Canadian
      provinces that were analyzed (P = .5). CONCLUSIONS: The time from HC submission
      to HC approval takes 3 months longer than the same time interval for the FDA. To
      the authors' knowledge, this is the first documentation of the time required to
      bring an oncology drug from HC submission to placement on a provincial drug
      formulary.

PMID- 25604016
TI  - [Current focus on clinical treatment of colorectal cancer].

PMID- 25604017
TI  - [The reconstruction of pelvic floor following extra-levator abdominoperineal
      excision of low rectal cancer: what's the optimal choice?].

PMID- 25604018
TI  - [The recognition to mesopancreas excision:surgical anatomy concept of
      standardization of regional lymph node dissection].

PMID- 25604019
TI  - [Impact of neoadjuvant radiochemotherapy followed by surgery for mid-low rectal
      cancer on patients' erectile function: a prospective randomized trial].
AB  - OBJECTIVE: To evaluate the erectile function of male patients treated by
      neoadjuvant radiochemotherapy and neoadjuvant chemotherapy alone for mid-low
      rectal cancer. METHODS: The clinical data of 66 patients with rectal cancer from
      March 2011 to March 2013 were prospectively analyzed. Of all the patients, 56
      cases were finally included in the study and were randomly allocated to two
      groups. Thirty patients were treated by neoadjuvant radiochemotherapy followed by
      surgery (RCS group), and 26 were treated by neoadjuvant chemotherapy followed by
      surgery (NCS group). The five-item version of the international index of erectile
      function (IIEF-5) questionnaire were used to determine erectile function before
      therapy and at least 12 months after surgery. The impacts of age, location, size
      of tumor, and body mass index on erectile function were analyzed. RESULTS: Total
      score was decreased significantly at follow-up compared to initial assessment in
      both RCS and NCS groups (23.4 +/- 1.30 vs. 11.7 +/- 5.8, t = 10.748, P < 0.01;
      23.1 +/- 1.3 vs. 15.2 +/- 6.7, t = 5.910, P < 0.01, respectively). Score
      difference was statistically higher in RCS group compared with NCS group (11.7 +/
      5.6 vs. 8.0 +/- 6.0, t = 2.394, P = 0.020). In terms of tumor location for RCS
      group, difference was statistically higher in the patients with low rectal cancer
      compared with those with middle rectal cancer (14.5 +/- 3.5 vs. 9.5 +/- 6.0, t =
      2.894, P = 0.008). CONCLUSIONS: The erectile functions of patients treated by
      neoadjuvant radiochemotherapy followed by surgery are more affected than that of
      patients treated by neoadjuvant chemotherapy followed by surgery in mid-low
      rectal cancer. Also low rectal cancer are significantly associated with erectile
      dysfunction in the patients treated by neoadjuvant radiochemotherapy followed by
      surgery.

PMID- 25604021
TI  - [Perioperative antibiotic prophylaxis in colorectal surgery: an investigation of
      2 465 cases].
AB  - OBJECTIVE: To investigate the influence of changes in perioperative antibiotic
      prophylaxis (PAP) duration in colorectal surgery on surgical site infection
      (SSI). METHODS: The data on PAP in April and October between 2011 and 2013 was
      collected from tertiary and secondary hospitals in Shanghai. Prevalence of SSI
      rates over the same period was compared. RESULTS: A total of 2 465 cases of
      colorectal surgeries were studied over the three-year period, including 1 784
      cases in tertiary hospitals and 681 cases in secondary hospitals. In 940 surgical
      operations, PAP duration were within 72 hours, accounting for 38.1% of all cases.
      48.0% of the operations in 2013 had a PAP within 72 hours, which is significantly
      higher than that of 20.8% seen in 2011 (chi(2) = 129.986, P = 0.000). In 2013,
      53.5% of the all procedures in tertiary hospitals had PAP <= 72 hours, compared
      with 35.5% in secondary hospitals over the same period (chi(2) = 22.714, P =
      0.000). Combined uses of nitroimidazoles, with an effect of anti-anaerobic, were
      used much more commonly in tertiary (76.0%) than in secondary hospitals (41.4%)
      (chi(2) = 267.820, P = 0.000). The usage of cephamycin were higher in secondary
      (20.6%) than in tertiary hospitals (4.7%) (chi(2) = 149.865, P = 0.000).
      According to the investigations by SICC on prevalence of healthcare-associated
      infections between 2011 and 2013, colorectal surgeries have an average SSI rate
      of 2.0%. Stratified data showed that the rate of PAP <= 72 hours increase from
      23.6% in 2011 to 45.8% in 2013 over the same period. However, the SSI rate did
      not show a significant change (1.9% in 2011, 1.7% in 2013). There was no linearly
      dependent between the two rates (r = 0.015, P = 0.990). CONCLUSIONS: The
      proportion of rational PAP of colorectal surgeries in Shanghai has increased.
      Perioperative antibiotic prophylaxis duration decreased, while SSI rates over the
      same period did not increase.

PMID- 25604020
TI  - [Feasibility and short-outcomes of laparoscopic extralevator abdominoperineal
      excision without changing position for distal rectal cancer].
AB  - OBJECTIVE: To evaluate the short-term outcomes of laparoscopic extralevator
      abdominoperineal excision (ELAPE) without changing position during operation.
      METHODS: Totally 51 patients with distal advanced rectal cancer received surgical
      operation in Peking Union Midical College Hospital from September 2011 to April
      2014. There were 29 male and 22 female patients with a mean age of (61 +/- 10)
      years. Twenty-six percent of the patients received preoperative concomitant
      chemotherapy and radiation. Twenty-seven patients underwent laparoscopic
      abdominoperineal excision (APE) procedure, while 24 patients underwent ELAPE
      procedure. In both groups, patients were kept Lithotomy-Trendelenburg position
      during operation. The fat tissue in ischialrectal fossa was not routinely
      removed, except the tumor invasion. All the patients' pelvic peritoneum was
      closed by continuous suturing, and subcutaneous tissue and skin by interrupted
      suturing. Retrospectively compare the pathoclinical features, operation time,
      bleeding, node retrieval, lateral margin and complications by t-text and chi(2)
      test respectively between ELAPE and APE procedures both by laparoscopic approach.
      RESULTS: No significant differences were found in term of age, gender, BMI,
      distance from anal verge, percentage of neoadjuvant chemoradiation, and TNM
      staging between these two groups (all P > 0.05). The operation time was
      significantly shorter in ELAPE group ((181 +/- 41) minutes vs. (228 +/- 58)
      minutes, t = -3.265, P = 0.002). The bleeding volume was less in ELAPEE group (50
      (80) ml vs 80 (100) ml (M(QR)), Z = -2.259, P = 0.024). The lateral margin,
      urinal retention and perineal wound healing were comparable for these two groups.
      No pelvic hernia was found during the postoperative follow-up (2 to 34 months) in
      both groups (all P > 0.05). CONCLUSIONS: Laparoscopic extralevator
      abdominoperineal excision without changing position is feasible for distal rectal
      cancer. Some essential steps can be simultaneously accomplished during operation
      without changing position. Closing the pelvic peritoneum is important for
      preventing the intestine dropping from abdominal cavity to presacral cavity.

PMID- 25604022
TI  - [A clinical study about applying different R1 criteria to evaluate pancreatic
      head ductal adenocarcinoma specimens].
AB  - OBJECTIVE: To analyze the R1 rate of the pancreatic head carcinoma resection
      specimens which delt with a unified protocol by two different R1 criteria.
      METHODS: Between November 2011 and October 2013, a unified pathological protocol
      was prospectively used to handle 70 consecutive pancreatioduodenectomy specimens
      for pancreatic ductal adenocarcinoma. Apart from the pancreatic transection
      margin, the bile duct and stomach/jejunum margins, different colors were used to
      stain the anterior surface, the superior mesenteric vein (SMV) groove margin, the
      superior mesenteric artery (SMA) margin, and the posterior surface. Axial slicing
      technique was used to dissect the pancreatioduodenectomy specimens. RESULTS:
      Among the 70 patients, 3, 30 and 37 patients were classified as well, moderately
      and poorly differentiated respectively;7, 15 and 48 patients were classified as
      pT1, pT2 and pT3 respectively.Forty patients (57.1%) had metastases in regional
      lymph nodes (pN1) , and 16 patients (22.9%) had metastases in para-aortic
      nodes.Resection of the portal vein and/or the superior mesenteric vein was
      performed in 13 patients (18.6%) .When applying the UICC criteria, 26 cancer
      resections were classified R1 (37.1%) , 33 margins were turned out to be R1. The
      SMV groove margin and SMA margin were infiltrated in 13 specimens (13/33, 39.4%)
      respectively.When applying the Royal College of Pathologist's criteria, 39 cancer
      resections were classified R1 (55.7%) , 51 margins were turned out to be R1. The
      SMV groove margin and SMA margin were infiltrated in 18 (18/51, 35.3%) and 19
      (19/51, 37.3%) specimen respectively.Until April 2014, the median follow-up was
      18(range 6-42) months. CONCLUSIONS: Applying the unified protocol for pancreatic
      head ductal adenocarcinoma specimens results in an significant R1 rate of the
      resection margins, and the R1 rate is related to the R1 criterion. The SMV groove
      margin and SMA margin are the two most frequent sites of R1.

PMID- 25604023
TI  - [Liver transplantation for irresectable hilar cholangiocarcinoma].
AB  - OBJECTIVE: To evaluate the outcome of patients with irresectable hilar
      cholangiocarcinoma undergoing orthotopic liver transplantation (OLT) and to
      identify the prognostic factors that could influence survival. METHODS: The data
      of 18 patients who underwent OLT for irresectable hilar cholangiocarcinoma
      between June 2003 and October 2010 were analyzed retrospectively. There were 12
      male and 6 female cases with median of 52 years(range from 34 to 65
      years).Fifteen patients underwent modified piggyback liver transplantation, 2
      patients underwent classical orthotopic liver transplantation and 1 patient
      underwent living donor liver transplantation. Data were evaluated regarding tumor
      size, pathologic stage, overall survival, recurrence rates and prognostic
      factors. RESULTS: OLT with lymphadenectomy was received by 18 patients with hilar
      cholangiocarcinoma. Median time until tumor recurrence was 20.5 months(range from
      6.0 to 33.0 months). Seventeen patients died during follow-up.Of these, 14
      patients died from recurrent or metastatic diseases, 2 patients died from
      multiple organ dysfunction syndrome during peri-operative period, and one patient
      died from other cause. The median survival time was 29.5 months(range from 3.0 to
      84.0 months). The overall survival rate and recurrence-free survival rate at 1,
      3, and 5 year were 16/18, 8/18, 1/18 and 13/18, 2/18, 1/18, respectively.Lymph
      node metastases had a statistically significant negative impact on overall
      survival. The 1, 3, and 5 year survival rates were 6/7, 1/7,0 and 10/11, 7/11,
      1/11 (P < 0.05) in lymph node-positive and lymph node-negative patients.
      CONCLUSIONS: Acceptable survival rates can be achieved by OLT for irresectable
      hilar cholangiocarcinoma without lymph node metastases.Strict patient selection
      plus multimodal chemoradiation therapy prior to OLT are recommend for patients
      with lymph node metastases.

PMID- 25604024
TI  - [The treatment of severe lumbar dysplastic spondylolisthesis].
AB  - OBJECTIVE: To summarize the clinical characteristics of severe lumbar dysplastic
      spondylolisthesis, and to investigate the effectiveness of the posterior surgery
      including decompression, partial reduction with instrumentations and interbody
      fusion. METHODS: Twelve patients of severe lumbar dysplastic spondylolisthesis
      treated between March 2007 and February 2012 were studied retrospectively. Twelve
      patients include 10 female and 2 male patients with an average age of 10.7 years
      (9-17 years). All of their spondylolisthetic level was L5 vertebrae. None of them
      were effective after regular conservative treatment. Eleven of 12 patients were
      treated surgically through a posterior decompression and instrumented reduction.
      One case was treated by L5 vertebrectomy and reduction of L4 onto sacrum. Their
      levels of instrumentations were L4-S1 in 8 patients and L5-S1 in 4 patients. All
      of 12 patients were fused via interbody fusion. The visual analog scale(VAS),
      Oswestry disability index (ODI), Japanese Orthopaedic Association(JOA) score,
      slip angle, percentage slip, lumbar lordosis, sagittal balance were used as
      outcome measures. RESULTS: All of these patients were followed up regularly with
      an average follow-up of 32 months (6-64 months). Five of these 12 patients
      suffered postoperative nerve root impairment, including impairment of unilateral
      and bilateral L5 nerve roots. At the latest follow-up, only 1 case was still
      suffering from the weakness of unilateral peroneal long and short muscles, the
      other 4 patients recovered totally. The degree of their spondylolisthesis was
      reduced II degrees or more, and their slip angles decreased from 35.6 degree
      preoperatively to 9.8 degree postoperatively. The VAS, ODI , JOA, lumbar lordosis
      and sagittal balance were improved postoperatively. No instrumentation loosening
      or rupture was found. CONCLUSIONS: In patients with severe lumbar dysplastic
      spondylolisthesis, isolated posterior decompression, reduction with internal
      fixation may lead to a satisfactory clinical outcomes. Surgical reduction is
      helpful to improve the interbody contact area, thus possibly improve the fusion
      rate. At the same time, reduction may reduce or correct the lumbar-sacral
      kyphosis, recover the normal lumbar lordosis and normal sagittal alignment with
      an excellent cosmetic result. The incidence of the postoperative nerve impairment
      is high because of the stretching of L5 nerve roots secondary to the reduction,
      but most of the patients with postoperative nerve impairment may recover
      gradually.

PMID- 25604025
TI  - [Clinical study of platelet-rich plasma gel in total knee arthroplasty].
AB  - OBJECTIVE: To investigate the effect of platelet-rich plasma (PRP) gel in total
      knee arthroplasty. METHODS: From January 2011 to January 2013, 30 patients of
      total knee arthroplasty were received PRP (PRP group) and 30 patients won't
      received PRP(normal saline group).Routine drainage and functional exercise were
      applied to the two groups after operation. Postoperative drainage volume,
      inflammatory reaction, grade of wound healed, Hospital for Special Surgery (HSS)
      Score for knee, the Feller Score for patella and range of motion (ROM) for knee
      were evaluated.Independent samples t-test, grade data used rank sum test were
      used to compared two groups. RESULTS: Postoperative drainage volume was (152 +/-
      22) ml in PRP group and (432 +/- 35) ml in normal saline group. Postoperative
      drainage volume were statistically significant difference between two groups (t =
      37.098, P < 0.05). At 4 days after operation, no inflammatory reaction was
      observed in 27 cases of PRP group and in 24 cases of normal saline group, mid
      inflammatory reaction in 2 cases of PRP group and in 4 cases of normal saline
      group, moderate inflammatory reaction in 1 cases of PRP group and in 2 cases of
      normal saline group.Wound healed by first intention in 30 patients of PRP group
      and in 29 patients of normal saline group (29/30), by second intention after 3
      days of dressing change in 1 patient of normal saline group using 75% alcohol wet
      compressed. The adverse reaction rate was 3.3%. The average follow-up period was
      16 months, ranging from 10 to 24 months. Three months postoperative HSS score for
      knee, scores of patellar, scores of anterior knee pain and ROM for knee were
      statistically significant difference in PRP group and normal saline group (t =
      2.288, 2.097, 2.630, 2.104; all P < 0.05). Inflammatory reaction, grade of wound
      healed, final follow-up HSS score for knee, scores of patellar, scores of
      anterior knee pain and ROM for knee had no statistically significant difference
      between PRP group and normal saline group (P > 0.05). CONCLUSIONS: Using PRP gel
      in total knee arthroplasty can reduce postoperative drainage volume, accelerate
      the healing of operation incision with no extra complications.It has good short
      term clinical effect.

PMID- 25604026
TI  - [Ultrasound-guided percutaneous radiofrequency ablation treatment for renal clear
      cell carcinoma].
AB  - OBJECTIVE: To investigate clinical outcomes of ultrasound-guided percutaneous
      radiofrequency ablation (USG-RFA) in patients with renal clear cell carcinoma.
      METHODS: Medical records of 34 patients who underwent USG-RFA of renal clear cell
      carcinoma at the Department of Urology of the Affiliated Drum Tower Hospital of
      Medical School of Nanjing University from May 2009 to January 2014 were
      retrospectively reviewed, including 28 male and 6 female patients aged between 25
      and 85 years (mean age 60.7 years). Of the included cases, 16 had tumors located
      in the left kidney, 16 in the right, 1 in the solitary kidney, and 1 in the
      bilateral kidney. There were 35 tumors in this study totally. The maximum
      diameter of the tumors was 1.8 to 5.0 cm (mean (2.7 +/- 0.3) cm), of which 32
      cases of renal tumors were <= 4.0 cm and 3 cases of renal tumors were > 4.0 cm to
      5.0 cm. Pathological diagnosis were acquired by ultrasound-guided percutaneous
      biopsy after USG-RFA. Contrast-enhanced ultrasound was used to evaluate tumor
      outcomes at the time of the surgery, and multi-slice spiral CT enhanced scan and
      contrast-enhanced ultrasound were used to identify residues and recurrences after
      treatment. RESULTS: Treatments for all the patients were finished with short
      postoperative hospital stay about 3-5 days. No complications related to USG-RFA
      were encountered in any of the cases, such as perirenal fluid collection,
      perirenal hematoma, and peripheral organ damage. All the cases were diagnosed as
      clear cell carcinoma according to pathological results. The mean follow-up period
      was 29 +/- 6 (range 3-59) months. Of the 35 USG-RFA-treated subjects, 32 tumors
      <= 4 cm reached the standard of complete treatment after one tumor was found with
      residue after the first month follow-up, and two tumors were noted recurrence at
      the 4 and 10 months follow-up after USG-RFA. Nonetheless, no residue or
      recurrence occurred after secondary treatment for these 3 tumors where
      pathological diagnosis were acquired again. The other 3 cases with tumors > 4.0
      cm to 5.0 cm underwent USG-RFA twice or three times before reaching the standard
      of complete treatment, of which two had twice and one tumor had three times
      treatments. There was no carcinoma residue or recurrence during follow-up period.
      CONCLUSIONS: Percutaneous ultrasound-guided radiofrequency ablation for small
      renal mass (SRM) has satisfied clinical outcomes, with the advantage of less
      injury, lower complication rates and shorter recovery time for small size of
      renal clear cell carcinoma. USG-RFA may become the preferred treatment
      alternative for SRM.

PMID- 25604027
TI  - Pirfenidone: a review of its use in idiopathic pulmonary fibrosis.
AB  - Pirfenidone (Esbriet(r)) is an orally administered, synthetic, pyridone compound
      that is approved for the treatment of adults with mild to moderate idiopathic
      pulmonary fibrosis (IPF) in the EU, and for the treatment of IPF in the USA. This
      article summarizes pharmacological, efficacy and tolerability data relevant to
      the use of pirfenidone in these indications. In the randomized, double-blind,
      placebo-controlled, multinational CAPACITY trials in patients with mild to
      moderate IPF, a significant reduction in the rate of decline in forced vital
      capacity (FVC) was seen with pirfenidone versus placebo in study 004 but not in
      study 006. Pirfenidone also reduced the rate of decline in FVC to a significantly
      greater extent than placebo in the randomized, double-blind, multinational ASCEND
      trial in this patient population. In addition, pirfenidone showed a significant
      treatment effect on the 6-min walking test distance and progression-free survival
      in the ASCEND trial and in a pooled analysis of the CAPACITY trials. Pirfenidone
      had a manageable tolerability profile in all three studies. Gastrointestinal and
      skin-related events (e.g. nausea, rash, photosensitivity reaction), which were
      the most commonly occurring treatment-emergent adverse events, were generally
      mild to moderate in severity. In addition, a prespecified mortality analysis
      across all three studies demonstrated a significant reduction in IPF-related and
      all-cause mortality with pirfenidone. In conclusion, oral pirfenidone is a
      valuable agent for use in patients with IPF.

PMID- 25604028
TI  - A time series based sequence prediction algorithm to detect activities of daily
      living in smart home.
AB  - OBJECTIVES: The goal of smart homes is to create an intelligent environment
      adapting the inhabitants need and assisting the person who needs special care and
      safety in their daily life. This can be reached by collecting the ADL (activities
      of daily living) data and further analysis within existing computing elements. In
      this research, a very recent algorithm named sequence prediction via enhanced
      episode discovery (SPEED) is modified and in order to improve accuracy time
      component is included. METHODS: The modified SPEED or M-SPEED is a sequence
      prediction algorithm, which modified the previous SPEED algorithm by using time
      duration of appliance's ON-OFF states to decide the next state. M-SPEED
      discovered periodic episodes of inhabitant behavior, trained it with learned
      episodes, and made decisions based on the obtained knowledge. RESULTS: The
      results showed that M-SPEED achieves 96.8% prediction accuracy, which is better
      than other time prediction algorithms like PUBS, ALZ with temporal rules and the
      previous SPEED. CONCLUSIONS: Since human behavior shows natural temporal
      patterns, duration times can be used to predict future events more accurately.
      This inhabitant activity prediction system will certainly improve the smart homes
      by ensuring safety and better care for elderly and handicapped people.

PMID- 25604029
TI  - "I don't mind damaging my own body" a qualitative study of the factors that
      motivate smokers to quit.
AB  - BACKGROUND: Although smoking prevalence in England has declined, one in five
      adults smoke. Smokers are at increased risk of a number of diseases, including
      COPD which affects an estimated 1.5 million people in England alone. This study
      aimed to explore issues relating to smoking behaviour and intention to quit that
      might be used to inform the development of cessation interventions. Issues
      explored included knowledge of smoking related disease, with a particular
      emphasis on Chronic Obstructive Pulmonary Disease (COPD). Understanding around
      risk of disease, including genetic risk was explored, as were features of
      appropriate and accessible cessation materials and support. METHODS: Semi
      structured interviews and focus groups were conducted with a total of 30
      individuals of which 17 were smoking cessation clients and 13 were professionals
      working within health care settings relevant to supporting smokers to quit. A
      largely purposive approach was taken to sampling, and data were analysed using
      the constant comparative method. RESULTS: Knowledge of the smoking related
      disease COPD was limited. Smokers' concerns around risk of disease were
      influenced by their social context and were more focussed on how their smoking
      might impact on the health of their family and friends, rather than how it might
      impact on them as individuals. Participants felt the provision of genetic risk
      information may have a limited impact on motivation to quit. Genetic risk was
      considered to be a difficult concept to understand, particularly as increased
      risk does not mean an individual will definitely develop disease. In terms of
      cessation approaches, the use of visual media was consistently supported, as was
      the use of materials that linked directly with life experiences. Images of
      children inhaling second hand smoke for example, had a particular impact.
      CONCLUSIONS: Public health messages around the risks of smoking and approaches to
      quitting should continue to have an emphasis on the dangers that an individual's
      smoking has on the lives of the people around them. More work also needs to be
      done to raise awareness around both the risk of COPD in smokers and the impact
      this disease has on quality of life and life expectancy.

PMID- 25604030
TI  - Our approach to changing the culture of caring for the acutely unwell patient at
      a large UK teaching hospital: A service improvement focus on Early Warning
      Scoring tools.
AB  - INTRODUCTION: Early Warning Scoring tools (EWS) play a major role in the
      detection of the deteriorating ward patient. EWS tools have been in place in
      Nottingham University Hospitals NHS Trust for over five years but compliance has
      been low. A service improvement project commenced across all admission wards in
      2013, initiated through a financially driven CQUIN. Prior to the project, only
      one out of five clinical care targets set were achieved. STRATEGY: An established
      framework for service improvement was used to guide delivery. The approach has
      consisted of multi-faceted, inter-professional high impact interventions
      including ward delivered education, human factors training and clinician
      feedback, combined with regular performance audits. RESULTS: Since introduction
      of the service improvement team, consistent signs of improvement have been
      visible across the admission areas in four out of five of the clinical care
      targets. CONCLUSION: The first 12 months of the project has seen tangible
      benefits in patient care and staff experience. Personal feedback both to medical
      and nursing staff has been effective where a top-down approach may not have been.

PMID- 25604031
TI  - A national quality improvement initiative for reducing harm and death from sepsis
      in Wales.
AB  - AIMS: The Rapid Response to Acute Illness (RRAILS) Programme is a quality and
      service improvement initiative which is participated in by all Welsh healthcare
      organisations including the Welsh Ambulance Service Trust (WAST) and Velindre
      Cancer Centre. The aims of the programme were and are: Implementing the National
      Early Warning Score (NEWS) as standard in all clinical areas in all 18 acute
      hospitals. Quantifying the incidence of sepsis and acute deterioration in the non
      Critical Care setting. Improving reliability of systems for identification,
      escalation and treatment of sepsis. Demonstrably improving outcomes from sepsis
      and other causes of acute deterioration. METHODS: Clinical teams participated in
      learning sets at which they were trained in service improvement and human factors
      principles and then supported to implement 'bundles' of best evidence whilst
      measuring both processes and outcomes. FINDINGS: All organisations have
      implemented standardised tools and operating procedures including NEWS, sepsis
      screening tools, Patient Status at A Glance (PSAG) boards, sepsis response bags
      and an antibiotic formulary. All organisations have demonstrated improvements in
      the reliability of detection and escalation of acute deterioration whilst many
      have started to demonstrate local improvements in outcomes. CONCLUSION: The
      collaborative learning set is an effective method for improving quality of sepsis
      care throughout a single healthcare economy.

PMID- 25604032
TI  - Magnetoresponsive virus-mimetic nanocapsules with dual heat-triggered sequential
      infected multiple drug-delivery approach for combinatorial tumor therapy.
AB  - Stimuli-responsive drug-delivery systems constitute an appealing approach to
      direct and restrict drug release spatiotemporally at the specific site of
      interest. However, it is difficult for most systems to affect every cancer cell
      in a tumor tissue due to the presence of the natural tumor barrier, leading to
      potential tumor recurrence. Here, core-shell magnetoresponsive virus-mimetic
      nanocapsules (VNs), which can infect cancer cells sequentially and double as a
      magnetothermal agent fabricated through anchoring iron oxide nanoparticles in a
      single-component protein (lactoferrin) shell, are reported. With large payload of
      hydrophilic/hydrophobic anticancer cargos, doxorubicin and palictaxel, VNs can
      simultaneously give a rapid drug release and intense heat while applying an
      external high-frequency magnetic field (HFMF). Furthermore, after being liberated
      from dead cells by HFMF manipulation, the constructive VNs can sequentially
      infect neighboring cancer cells and deliver sufficient therapeutic agents to next
      targeted sites. With high efficiency for sequential cell infections, VNs have
      successfully eliminated subcutaneous tumor after a combinatorial treatment. These
      results demonstrate that the VNs could be used for locally targeted, on-demand,
      magnetoresponsive chemotherapy/hyperthermia, combined with repeated cell
      infections for tumor therapy and other therapeutic applications. 

PMID- 25604033
TI  - A Low-Affinity K+ Transporter AlHKT2;1 from Recretohalophyte Aeluropus lagopoides
      Confers Salt Tolerance in Yeast.
AB  - The high-affinity potassium transporters (HKT) are highly important for stress
      tolerance in plants as they uniquely maintain K(+)/Na(+) ratio for their survival
      and growth. In this study a novel HKT gene AlHKT2;1 was isolated and
      characterized from salt secreting halophyte, Aeluropus lagopoides. The AlHKT2;1
      cDNA comprised of an open reading frame of 1,581 bp, encoding a protein of 526
      amino acid residues. It belongs to class II HKTs and showed high homology with
      other HKT genes. Functional characterization of AlHKT2;1 in both K(+) uptake
      deficient (WDelta6) and Na(+)-sensitive yeast mutants (G19) showed the
      characteristic feature of low-affinity K(+) transporter supporting the growth at
      >1 mM KCl concentration. The transformed yeast cells showed high sensitivity to
      NaCl; however, the addition of KCl along with NaCl support the growth of AlHKT2;1
      expressing mutant. Ion content analysis of yeast cells with AlHKT2;1 grown in
      high NaCl medium supplemented with KCl revealed that salt tolerance was
      correlated with accumulation of K(+) during salt stress. These results suggest
      that AlHKT2;1 plays an important role in the K(+) uptake during salt stress and
      in maintaining a high K(+)/Na(+) ratio in the cytosol.

PMID- 25604036
TI  - Maternal outcomes after uterine balloon tamponade for postpartum hemorrhage.
AB  - OBJECTIVE: To evaluate maternal outcomes following uterine balloon tamponade in
      the management of postpartum hemorrhage. DESIGN: Retrospective case-series.
      SETTING: Two French hospitals, a level 3 university referral center and a level 2
      private hospital. POPULATION: All women who underwent balloon tamponade treatment
      for primary postpartum hemorrhage. METHODS: Uterine tamponade was used after
      standard treatment of postpartum hemorrhage had failed. The study population was
      divided into two groups, successful cases where the bleeding stopped after the
      balloon tamponade, and failures requiring subsequent surgery or embolization.
      MAIN OUTCOME MEASURES: Success rates. RESULTS: Uterine tamponade was used in 49
      women: 30 (61%) after vaginal delivery and 19 (39%) after cesarean section.
      Uterine atony was the main cause of hemorrhage (86%). The overall success rate
      was 65%. Of 17 failures, surgery was required in 16 cases, including hysterectomy
      in 11, and uterine artery embolization in one case. Demographic and obstetric
      characteristics did not differ significantly between the success and failure
      groups. No complications were directly attributed to the balloon tamponade in the
      postpartum period. Two women had a subsequent full-term pregnancy without
      recurrence of postpartum hemorrhage. CONCLUSIONS: Balloon tamponade is an
      effective, safe and readily available method for treating primary postpartum
      hemorrhage and could reduce the need for invasive procedures.

PMID- 25604034
TI  - Complement factor B activation in patients with preeclampsia.
AB  - Preeclampsia is a leading cause of maternal and fetal morbidity and mortality.
      Bb, the active fragment of complement factor B (fB), has been reported to be a
      predictor of preeclampsia. However, conflicting results have been found by some
      investigators. We hypothesized that the disagreement in findings may be due to
      the racial/ethnic differences among various study groups, and that fB activation
      is significant in women of an ethnic minority with preeclampsia. We investigated
      the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women
      of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant
      women (96% of an ethnic minority, including 78% African-American). Thirteen
      percent of these were diagnosed with preeclampsia. Maternal venous blood was
      collected from all participants together with fetal umbilical cord blood samples
      from 154 deliveries in the 291 women. The results were analyzed using the Mann
      Whitney U test and multivariate analyses. Maternal Bb levels were significantly
      higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb
      in fetal cord blood were similar in both groups. Subgroup analyses of African
      American patients' results confirmed the study hypothesis that there would be a
      significant increase in Bb in the maternal blood of the preeclamptic group and no
      increase in Bb in the fetal cord blood of this group. These results suggest that
      a maternal immune response through complement fB might play a role in the
      development of preeclampsia, particularly in African-American patients. 

PMID- 25604035
TI  - Complexes of platelet factor 4 and heparin activate Toll-like receptor 4.
AB  - BACKGROUND: In some patients, the anticoagulant heparin elicits formation of
      antibodies that can cause the life and/or limb-threatening syndrome known as
      heparin-induced thrombocytopenia (HIT). HIT antibodies target complexes formed at
      specific molar ratios of heparin and platelet factor 4 (PF4). The unpredictable
      occurrence and the mechanism of this atypical immune response to PF4:heparin
      complexes are poorly understood. OBJECTIVE: We investigated whether complexes
      formed at specific PF4:heparin ratios (PHRs) might resemble molecular patterns
      associated with host defense responses. METHODS: We used an in vitro cytokine
      release assay to determine whether defined PHRs caused cytokine release from
      human whole blood. Lipopolysaccharide (LPS) was used as a positive assay control,
      and some experiments included antibodies to block Toll-like receptor 4 (TLR4).
      RESULTS: PF4:heparin complexes caused release of the biomarker interleukin 8 in
      whole blood, and the level of response varied with the stoichiometric ratio of
      PF4 to heparin. The profile of response to LPS and to PF4:heparin complexes
      varied among blood donors, and the interleukin 8 response to both LPS and
      PF4:heparin was inhibited by TLR4-blocking antibodies. CONCLUSIONS: Specific PF4
      heparin complexes can elicit a TLR4-mediated response, suggesting that these
      complexes can mimic a pathogen-associated molecular pattern, and supporting the
      suggestion that the HIT immune response represents a misdirected host defense
      mechanism.

PMID- 25604037
TI  - Thermostable alpha-amylase immobilization: Enhanced stability and performance for
      starch biocatalysis.
AB  - The uses of thermostable starch hydrolytic biocatalysts are steadily increasing
      for the industrial application because of their obvious need for biocatalytic
      performance at elevated temperatures. The starch liquefaction and
      saccharification can be carried out simultaneously by the use of thermostable
      starch hydrolytic biocatalysts, thus minimizing the unit operations, time, and
      efforts. The cost factor hampers the industrialization of expensive soluble
      (free) enzymes for biocatalytic applications and the immobilization of enzymes
      offers promising alternative to the hurdle. The present investigation was aimed
      for immobilization of thermostable alpha-amylase using calcium alginate, and
      statistical optimization studies were carried out for enhanced biocatalytic
      performance. Initially, one-parameter at a time optimization studies were carried
      out for identification of significant factors influencing the immobilization.
      Furthermore, a statistical approach, response surface methodology, was applied
      for immobilization of alpha-amylase. The immobilized alpha-amylase in alginate
      microbeads showed enhanced stability to temperature and reusable property for up
      to seven cycles (with the retention of 50% initial activity). Finally, the
      kinetic behavior of free and immobilized enzyme showed the Km value of 1.2% and
      2.6% (w/v) and Vmax of 1,020 and 1,030 U, respectively. Fifty percent reduction
      in affinity of the immobilized enzyme toward substrate was compensated by its
      longer stability. 

PMID- 25604038
TI  - Low-energy dielectric screening in Pd and PdHx systems.
AB  - Modifications in dielectric properties of palladium upon absorption of hydrogen
      are investigated theoretically in the low-energy (0-2 eV) region. The
      calculations were performed with full inclusion of the electronic band structure
      obtained within a self-consistent pseudopotential approach. In particular, we
      trace the evolution of the acoustic-like plasmon (AP) found previously in clean
      Pd with increasing hydrogen concentration. It exists in PdHx up to the hydrogen
      content x corresponding to the complete filling of the 4d Pd-derived energy bands
      because of the presence of two kinds of carriers at the Fermi surface. At higher
      H concentration the AP disappears since only one kind of carrier within the sp
      like energy band exists at the Fermi level. Additionally, we investigate the
      spatial distribution inside the crystal of a potential caused by a time-dependent
      external perturbation and observe drastic modifications in the screening
      properties in the PdHx systems with energy and with hydrogen concentration.

PMID- 25604039
TI  - Dynamic cortical lateralization during olfactory discrimination learning.
AB  - Bilateral cortical circuits are not necessarily symmetrical. Asymmetry, or
      cerebral lateralization, allows functional specialization of bilateral brain
      regions and has been described in humans for such diverse functions as
      perception, memory and emotion. There is also evidence for asymmetry in the human
      olfactory system, although evidence in non-human animal models is lacking. In the
      present study, we took advantage of the known changes in olfactory cortical local
      field potentials that occur over the course of odour discrimination training to
      test for functional asymmetry in piriform cortical activity during learning. Both
      right and left piriform cortex local field potential activities were recorded.
      The results obtained demonstrate a robust interhemispheric asymmetry in anterior
      piriform cortex activity that emerges during specific stages of odour
      discrimination learning, with a transient bias toward the left hemisphere. This
      asymmetry is not apparent during error trials. Furthermore, functional
      connectivity (coherence) between the bilateral anterior piriform cortices is
      learning- and context-dependent. Steady-state interhemispheric anterior piriform
      cortex coherence is reduced during the initial stages of learning and then
      recovers as animals acquire competent performance. The decrease in coherence is
      seen relative to bilateral coherence expressed in the home cage, which remains
      stable across conditioning days. Similarly, transient, trial-related
      interhemispheric coherence increases with task competence. Taken together, the
      results demonstrate transient asymmetry in piriform cortical function during
      odour discrimination learning until mastery, suggesting that each piriform cortex
      may contribute something unique to odour memory.

PMID- 25604041
TI  - Cord blood FGF21 in gestational diabetes and its relationship with postnatal
      growth.
AB  - BACKGROUND/OBJECTIVES: To study whether FGF21 was present in cord blood and
      explore its relationship with maternal variables and postnatal growth. SUBJECTS
      AND METHODS: The study included 157 pregnant women at the beginning of the third
      trimester; 79 with gestational diabetes (GDM), 78 with normal glucose tolerance
      (NGT), and their offspring. Glucose metabolism was assessed by oral glucose
      tolerance test. Insulin resistance was assessed by homeostasis model assessment
      index-insulin resistance (HOMA-IR). FGF21 was determined in maternal plasma drawn
      at recruitment and in cord blood obtained at delivery. Offspring weight and
      height was assessed at birth and at 12, 24 and 48 months. RESULTS: Maternal FGF21
      was higher in gestational diabetes than in the normal glucose-tolerant group,
      whereas similar cord blood FGF21 levels were observed in both groups. Lower cord
      blood FGF21 was strongly positively correlated with maternal circulating levels.
      This relationship was independent of mother's prepregnancy body mass index (BMI),
      glucose levels and HOMA-IR. Although maternal FGF21 levels were correlated with
      prepregnancy BMI and HOMA-IR index, no relationship was observed between FGF21
      and birth weight. However, cord blood FGF21 levels were correlated with BMI Zeta
      Score at 12 and 24 months, and this relationship became stronger when only the
      NGT group was analyzed. CONCLUSION: FGF21 is present in human cord blood, and its
      levels are closely correlated with maternal levels. The association observed
      between cord blood FGF21 and postnatal BMI may suggest a potential role during
      intrauterine life that may influence future metabolic imbalance.

PMID- 25604040
TI  - Malaria parasite carriage and risk determinants in a rural population: a
      malariometric survey in Rwanda.
AB  - BACKGROUND: Based on routine health facility case data, Rwanda has achieved a
      significant malaria burden reduction in the past ten years. However, community
      based malaria parasitaemia burden and reasons for continued residual infections,
      despite a high coverage of control interventions, have yet to be characterized.
      Measurement of malaria parasitaemia rates and evaluation of associated risk
      factors among asymptomatic household members in a rural community in Rwanda were
      conducted. METHODS: A malariometric household survey was conducted between June
      and November 2013, involving 12,965 persons living in 3,989 households located in
      35 villages in a sector in eastern Rwanda. Screening for malaria parasite
      carriage and collection of demographic, socio-economic, house structural
      features, and prior fever management data, were performed. Logistic regression
      models with adjustment for within- and between-households clustering were used to
      assess malaria parasitaemia risk determinants. RESULTS: Overall, malaria
      parasitaemia was found in 652 (5%) individuals, with 518 (13%) of households
      having at least one parasitaemic member. High malaria parasite carriage risk was
      associated with being male, child or adolescent (age group 4-15), reported
      history of fever and living in a household with multiple occupants. A malaria
      parasite carriage risk-protective effect was associated with living in households
      of, higher socio-economic status, where the head of household was educated and
      where the house floor or walls were made of cement/bricks rather than
      mud/earth/wood materials. Parasitaemia cases were found to significantly cluster
      in the Gikundamvura area that neighbours marshlands. CONCLUSION: Overall, Ruhuha
      Sector can be classified as hypo-endemic, albeit with a particular 'cell of
      villages' posing a higher risk for malaria parasitaemia than others. Efforts to
      further reduce transmission and eventually eliminate malaria locally should focus
      on investments in programmes that improve house structure features (that limit
      indoor malaria transmission), making insecticide-treated bed nets and indoor
      residual spraying implementation more effective.

PMID- 25604042
TI  - Association between body mass index and diabetic retinopathy in Chinese patients
      with type 2 diabetes.
AB  - AIMS: To explore the factors mediating the relationship between body mass index
      (BMI) and diabetic retinopathy (DR) in Chinese type 2 diabetes patients. METHODS:
      This is a cross-sectional study. Data of 2,533 patients with type 2 diabetes were
      studied from the Shanghai Diabetes Registry Database. DR was assessed using non
      mydriatic fundus photography and graded as non-DR, mild-moderate (DR I-II), and
      sight-threatening (DR III-IV). BMI (kg/m(2)) was classified as normal weight
      (18.5 <= BMI < 25), overweight (25 <= BMI < 30), and obese (BMI >= 30). beta cell
      function was evaluated by fasting C-peptide (FCP). RESULTS: DR was present in 701
      (27.7 %) patients. Patients with DR had lower BMI (24.3 vs. 24.9 kg/m(2), P =
      0.001) and fasting C-peptide (1.46 vs. 1.86 ng/ml, P < 0.001) than those without
      DR. The association between BMI (2 kg/m(2) interval) and DR was U-shaped;
      patients with BMI 28-29.9 kg/m(2) had the lowest DR rate. Compared with normal
      weight, overweight was associated with reduced risk of any DR [odds ratio (OR)
      0.73], DR I-II (OR 0.76), and DR III-IV (OR 0.64) after adjustment for sex, age
      at diabetes diagnosis, and duration of diabetes. This negative association
      attenuated after adjustment for other confounders and became nonsignificant after
      further adjustment for FCP. Patients with different BMI categories had similar DR
      risk when stratified by FCP tertiles. CONCLUSION: Overweight patients have lower
      DR prevalence than normal weight individuals, which may be attributable to better
      beta cell function in overweight patients.

PMID- 25604044
TI  - An N-heterocyclic carbene phenanthroline ligand: synthesis, multi-metal
      coordination and spectroscopic studies.
AB  - Dimetal complexes of a new N-heterocyclic carbene/phenanthroline ligand have been
      synthesized. Coordination of both ruthenium and rhenium to the phenanthroline
      moiety in combination with platinum at the carbene moiety are reported. Steady
      state and time-resolved optical absorption and photoluminescence spectra were
      obtained for the complexes. These results illustrate significant changes occur
      with the incorporation of the second metal, and that the specific metal bound to
      the phenanthroline moiety is important to the photophysical characteristics of
      this system. 

PMID- 25604043
TI  - Echo time dependence of observed T1 in the human lung.
AB  - BACKGROUND: This work is intended to demonstrate that T1 measured in the lungs
      depends on the echo time (TE) used. Measuring lung T1 can be used to gain
      quantitative morphological and functional information. It is also shown that this
      dependence is particularly visible when using an ultra-short TE (UTE) sequence
      with TE well below 1 ms for T1 quantification in lung tissue, rather than
      techniques with TE on the order of 1-2 ms. METHODS: The lungs of 12 healthy
      volunteers (aged 22 to 33 years) were examined at 1.5 Tesla. A segmented
      inversion recovery Look-Locker multi-echo sequence based on two-dimensional UTE
      was used for independent T1 quantification at five TEs between TE1  = 70 MUs and
      TE5  = 2.3 ms. RESULTS: The measured T1 was found to increase gradually with TE
      from 1060 +/- 40 ms at TE1 to 1389 +/- 53 ms at TE5 (P < 0.001). CONCLUSION:
      Measuring T1 at ultra-short echo times reveals a significant dependence of
      observed T1 on the echo time. Thus, any comparison of T1 values should also
      consider the TEs used. However, this dependence on TE could also be exploited to
      gain additional diagnostic information on the tissue compartments in the lung.

PMID- 25604046
TI  - Plasmonic photosensitization of polyaniline prepared by a novel process for high
      performance flexible photodetector.
AB  - We report the synthesis of a polyaniline (PAni)-gold nanoparticle (AuNP)
      composite thin film in a single step. A flexible high-performance visible
      photodetector is constructed using PAni-AuNP composite with low loading of AuNP,
      and optoelectronic properties of the device are evaluated. The present study
      demonstrates that a plasmonic hybrid nanocomposite prepared by a single-step
      novel plasma-based dry process could solve the low lifetime and performance
      related issues of organic optoelectronic devices. 

PMID- 25604045
TI  - British HIV Association guidelines for the management of HIV infection in
      pregnant women 2012 (2014 interim review).

PMID- 25604048
TI  - NMO?TPB: a selectivity variation on the Ley-Griffith TPAP oxidation.
AB  - A non-hygroscopic tetraphenylborate salt of N-methylmorpholine-N-oxide (NMO) is
      reported (NMO?TPB), which modulates the standard Ley-Griffith oxidation such that
      benzylic and allylic alcohols are oxidised selectively. An attractive feature of
      this new protocol is that anhydrous conditions are not required for this
      selective tetra-n-propylammonium perruthenate (TPAP) oxidation, superseding the
      requirement of molecular sieves. 

PMID- 25604047
TI  - Increased circulating Th17 cells and elevated serum levels of TGF-beta and IL-21
      are correlated with human non-segmental vitiligo development.
AB  - Although non-segmental vitiligo (NSV) results from the autoimmune destruction of
      melanocytes, the detailed immune mechanisms have not yet been fully elucidated.
      Th17 cells have been identified to be implicated in human autoimmune diseases. In
      this study, the frequencies of peripheral blood Th17 cells and serum levels of IL
      17A and Th17 cell-related cytokines were examined in 45 patients with active NSV
      compared to 45 race-, gender-, and age-matched healthy controls. Our results
      showed increased circulating Th17 cell frequencies and elevated serum IL-17A, TGF
      beta1, and IL-21 levels in patients with NSV. Meanwhile, the increased Th17 cell
      frequencies are positively correlated with serum TGF-beta1 level, and the body
      surface area of lesions is positively correlated with elevated TGF-beta1 and IL
      21 levels and Th17 cell frequencies. Furthermore, positive correlation was
      identified between Th17 and Th1 cell frequencies in patients with NSV. These
      results further indicate the potential involvement of Th17 cells and the
      collaborative contribution of Th17 and Th1 in NSV development, and suggest that
      the elevated serum TGF-beta1 and IL-21 levels could contribute to enhanced Th17
      cell differentiation in NSV. 

PMID- 25604049
TI  - Transition-metal-free persulfuration to construct unsymmetrical disulfides and
      mechanistic study of the sulfur redox process.
AB  - A sulfur redox process has been developed between sulfinate and thiosulfate,
      which efficiently affords diverse unsymmetrical disulfides and provides a new
      method to modify pharmaceuticals and natural products without requiring an extra
      oxidant or reductant. Gram-scale investigation further demonstrates the
      practicality and application potential of this process. Isolated key
      intermediates and a series of control experiments afford an unusual process,
      which reveals the mechanism of comproportionation and the transition-metal-free
      sulfur redox process. 

PMID- 25604051
TI  - Changes in antenna sizes of photosystems during state transitions in granal and
      stroma-exposed thylakoid membrane of intact chloroplasts in Arabidopsis mesophyll
      protoplasts.
AB  - In chloroplasts of plants and algae, state transition is an important regulatory
      mechanism to maintain the excitation balance between PSI and PSII in the
      thylakoid membrane. Light-harvesting complex II (LHCII) plays a key role as the
      regulated energy distributor between PSI and PSII. It is widely accepted that
      LHCII, which is bound to PSII localized mainly in the granal thylakoid, migrates
      to bind with PSI localized mainly in the stroma-exposed thylakoid under
      preferential excitation of PSII. The phenomena have been extensively
      characterized by many methods. However, the exchange of LHCII between PSII and
      PSI has not been directly observed in vivo at physiological temperatures. Herein
      we applied fluorescence spectromicroscopy to Arabidopsis mesophyll protoplasts in
      order to observe in vivo changes in fluorescence spectra of granal and stromal
      thylakoid regions during the state transition. The microscopic fluorescence
      spectra obtained from a few sections with different depths were decomposed into
      PSI and PSII spectra and self-absorption effects were removed. We were able to
      determine amplitude changes of PSI and PSII in fluorescence spectra solely due to
      state transition. Subdomain analysis of granal and stromal thylakoid regions
      clarified variant behaviors in the different regions. 

PMID- 25604050
TI  - Expression of heterologous xyloglucan xylosyltransferases in Arabidopsis to
      investigate their role in determining xyloglucan xylosylation substitution
      patterns.
AB  - MAIN CONCLUSION: Putative XyG xylosyltransferases from Tropaeolum majus
      (nasturtium) and Solanum lycopersicum (tomato) homologous to characterized
      Arabidopsis genes were identified and shown to functionally complement
      Arabidopsis mutants lacking xyloglucan demonstrating they represent xyloglucan
      xylosyltransferases. Xyloglucan is a major hemicellulose in the plant cell wall
      and is important for the structural organization of the wall. The fine structure
      of xyloglucan can vary dependent on plant species and tissue type. Most vascular
      seed-bearing plants including Arabidopsis thaliana and nasturtium (Tropaeolum
      majus) have a xyloglucan structure, in which three out of four backbone glucosyl
      residues are substituted with xylosyl-residues. In contrast, the xyloglucan found
      in plants of the Solanaceae family, which includes tomato (Solanum lycopersicum),
      is typically less xylosylated with only two of the four backbone glucosyl
      residues substituted with xylosyl-residues. To investigate the genetics of
      xyloglucan xylosylation, candidate xyloglucan xylosyltransferase genes (XXTs)
      homologous to known A. thaliana XXTs were cloned from nasturtium and tomato.
      These candidate XXTs were expressed in the A. thaliana xxt1/2 double and xxt1/2/5
      triple mutant, whose walls lack detectable xyloglucan. Expression of the
      orthologs of XXT5 resulted in no detectable xyloglucan in the transgenic A.
      thaliana plants, consistent with a lack of xyloglucan in the A. thaliana xxt1/2
      double mutant. However, transformation of both the tomato and nasturtium
      orthologs of AtXXT1 and AtXXT2 resulted in the production of xyloglucan with a
      xylosylation pattern similar to wild type A. thaliana indicating that both SlXXT2
      and TmXXT2 likely have xylosyltransferase activity. As the expression of the
      SlXXT2 did not result in xyloglucan with a decreased xylosylation frequency found
      in tomato, this gene is not responsible for the unique xylosylation pattern found
      in the solanaceous plants.

PMID- 25604052
TI  - Regulation of aquaporin-mediated water transport in Arabidopsis roots exposed to
      NaCl.
AB  - The effects of Ca(NO3)2, KF and okadaic acid (OA) on cell hydraulic responses to
      NaCl were examined in roots of Arabidopsis thaliana wild-type plants and compared
      with plants overexpressing plasma membrane intrinsic protein PIP2;5. Root
      treatment with 10 mM NaCl rapidly and sharply reduced cell hydraulic conductivity
      (L(p)) in the wild-type Arabidopsis plants, but had no effect on L(p) in
      Arabidopsis plants overexpressing PIP2;5, suggesting that changes in protein and
      aquaporin gene expression were among the initial targets responsible for the
      inhibition of L(p) by NaCl. The down-regulation of PIP transcripts after 1 h
      exposure to 10 mM NaCl was likely a significant factor in the reduction of L(p).
      The effect of NaCl on L(p) in the wild-type plants was abolished when the NaCl
      treated roots were subsequently exposed to 5 mM KF, 5 mM Ca(NO3)2 and 5 uM OA.
      The reduction of L(p) by 5 mM KF could not be prevented by treatment with 5 mM
      Ca(NO3)2 in both wild-type and PIP2;5-overexpressing plants. However, 5 uM OA,
      which was added following NaCl or KF treatment, completely reversed L(p) within
      several minutes. The results provide evidence for high sensitivity of aquaporin
      mediated water transport to relatively low NaCl concentrations and point to the
      phosphorylation and/or dephosphorylation processes as those that are likely
      responsible for the protection of L(p) by fluoride and calcium treatments against
      the effects of NaCl.

PMID- 25604053
TI  - Retracted: 147 reduced syntaxin-5 in skeletal muscle of patients with type 2
      diabetes. A link between lipid storage and insulin resistance.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This abstract has been
      retracted at the request of Jan Boren, co-author, because of conscious
      fabrication, corruption or suppression of basic material and conscious
      preparation and presentation of falsified results in the abstract by one of the
      authors. 

PMID- 25604054
TI  - Congenital vascular rings: a clinical challenge for the pediatrician.
AB  - Vascular rings are congenital anomalies that lead to variable degrees of
      respiratory problems or feeding difficulties by forming a complete or partial
      ring compressing the trachea, the bronchi, and the esophagus. The clinical
      diagnosis of vascular rings is often challenging for the pediatrician because the
      clinical manifestations are heterogeneous and nonspecific. Symptoms can vary from
      wheezing, stridor, dyspnea, and/or dysphagia to life-threatening conditions;
      however, they may not be present. The aim of this study is to review the recent
      literature on this subject and describe new developments in diagnostics and
      imaging.

PMID- 25604055
TI  - Paradigm shift in activity assessment of IgA nephropathy - optimizing the next
      generation of diagnostic and therapeutic maneuvers via glycan targeting.
AB  - INTRODUCTION: IgA nephropathy (IgAN) is the most common glomerular disease and
      has a poor prognosis. Appropriate therapeutic strategies are not currently
      available due to the lack of information regarding IgAN pathogenesis and the
      absence of appropriate tools to assess disease activity in IgAN, a long-term
      chronic disease. However, recent evidence revealed that aberrantly glycosylated
      serum IgA1, mostly galactose-deficient IgA1 (Gd-IgA1) and immune complexes (ICs)
      with autoantibodies against glycan-containing epitopes on Gd-IgA1 are essential
      effector molecules. AREAS COVERED: Assessing disease activity by urinalysis/renal
      biopsy has some limitations, resulting in conflicts regarding the efficacy of
      possible IgAN-specific therapies. We summarize the characteristics and molecular
      basis of Gd-IgA1 and related ICs, their clinical application for activity
      assessment and early diagnosis, and discuss glycan as a potent target of
      therapeutic agents based on glycan engineering in IgAN. EXPERT OPINION: Recently,
      Gd-IgA1 and related ICs have shown clinical value for disease activity assessment
      and IgAN diagnosis. This suggests a paradigm shift in IgAN treatment thus
      allowing development of appropriate clinical trials of patients with IgAN stages
      and objective evaluation of the efficacy of future treatments. Early screening
      and diagnosis may increase therapeutic options, including quantitative regulation
      of nephritogenic Gd-IgA1 using therapeutic antibodies and selective depletion of
      Gd-IgA1-producing cells via glycan engineering.

PMID- 25604056
TI  - Contact dermatitis caused by polyethylene glycol-7 monooleate.

PMID- 25604057
TI  - Erratum to: 16(th) Annual Hernia Repair, Las Vegas.

PMID- 25604059
TI  - FAT FLUX: enzymes, regulators, and pathophysiology of intracellular lipolysis.
AB  - The great 19(th) century French physiologist Claude Bernard reasoned "Man can
      learn nothing except by going from the known to the unknown". This premise is
      particularly applicable to the progression of discoveries made in the field of
      fat metabolism since Bernard's time. Beginning with his groundbreaking discovery
      of fat digestion (later termed "lipolysis") in 1848, research addressing the
      basic processes of cellular storage and mobilization of fat has steadily
      advanced. Even after 150 years of research dedicated to lipolysis, exciting new
      principles have continued to emerge in the last 10 years. This Perspective
      summarizes these recent landmark discoveries in the field and emphasizes their
      relevance for the pathogenesis of extremely prevalent diseases such as obesity,
      heart disease, and cancer.

PMID- 25604058
TI  - Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic
      inflammation in age-related macular degeneration.
AB  - Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive
      signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes
      in the subretinal space. Age-related macular degeneration (AMD) is associated
      with a breakdown of the subretinal immunosuppressive environment and chronic
      accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD
      patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1(-/
      ) mice that develop MP accumulation on the RPE, photoreceptor degeneration, and
      increased choroidal neovascularization similarly express high levels of APOE.
      ApoE deletion in Cx3cr1(-/-) mice prevents pathogenic age- and stress-induced
      subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6
      in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor
      cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP
      survival. This mechanism may account, in part, for the MP accumulation observed
      in Cx3cr1(-/-) mice. Our results underline the inflammatory role of APOE in
      sterile inflammation in the immunosuppressive subretinal space. They provide
      rationale for the implication of IL-6 in AMD and open avenues toward therapies
      inhibiting pathogenic chronic inflammation in late AMD. 

PMID- 25604060
TI  - Achalasia and chronic opiate use: innocent bystanders or associated conditions?
AB  - High-resolution manometry identifies three subtypes of achalasia. However, type 3
      differs from classic achalasia. Although opiates affect esophageal motility,
      opiate use and achalasia have not been studied. Patients with a new diagnosis of
      achalasia at Mayo Clinic Rochester between June 1, 2012 and January 3, 2014 were
      identified. Clinical records were reviewed to assess symptoms, opiate use, and
      therapy. Fifty-six patients with achalasia were identified, 14 (25%) were on
      opiates. Opiate prescription was unrelated to achalasia in all cases, with
      chronic back and joint pain constituting the majority. Of patients on opiates,
      five (36%) had type 3 achalasia compared with four (10%) not on opiates (P =
      0.02). No patients on opiates had type 1 achalasia. Clinical presentation did not
      differ with opiates, although those on opiates were more likely to report chest
      pain (39 vs. 14%, P = 0.05) and less likely to have esophageal dilation (62 vs.
      82%, P = 0.13), none with greater than 5-cm diameter. Contractile vigor was
      greater with opiate use, with distal contractile integral of 7149 versus 2615.5
      mmHg/cm/second (P = 0.08). Treatment response was inferior on opiates, with
      persistent symptoms in 22% compared with 3% without opiates (P = 0.06). Opiate
      use is common in type 3 achalasia, with the majority of patients on opiates. No
      patients on opiates were diagnosed with type 1 achalasia. Manometric findings of
      type 3 achalasia mimic those induced by opiates, suggesting a physiologic
      mechanism for opiate induced type 3 achalasia. Treatment outcome is inferior with
      opiates, with opiate cessation perhaps preferable. Further studies assessing
      opiate use and achalasia are needed. 

PMID- 25604061
TI  - Replacing rubber plantations by rain forest in Southwest China--who would gain
      and how much?
AB  - The cultivation of rubber trees in Xishuangbanna Prefecture in China's Yunnan
      Province has triggered an unprecedented economic development but it is also
      associated with severe environmental problems. Rubber plantations are encroaching
      the indigenous rain forests at a large scale and a high speed in Xishuangbanna.
      Many rare plant and animal species are endangered by this development, the
      natural water management is disturbed, and even the microclimate in this region
      has changed over the past years. The present study aims at an assessment of the
      environmental benefits accruing from a reforestation project partly reversing the
      deforestation that has taken place over the past years. To this end, a Contingent
      Valuation survey has been conducted in Xishuangbanna to elicit local residents'
      willingness to pay for this reforestation program that converts existing rubber
      plantations back into forest. It is shown that local people's awareness of the
      environmental problems caused by increasing rubber plantation is quite high and
      that in spite of the economic advantages of rubber plantation there is a positive
      willingness among the local population to contribute financially to a reduction
      of existing rubber plantations for the sake of a partial restoration of the local
      rain forest. These results could be used for the practical implementation of a
      Payments for Eco-System Services system for reforestation in Xishuangbanna. 

PMID- 25604062
TI  - Response of the regression tree model to high resolution remote sensing data for
      predicting percent tree cover in a Mediterranean ecosystem.
AB  - Percent tree cover is the percentage of the ground surface area covered by a
      vertical projection of the outermost perimeter of the plants. It is an important
      indicator to reveal the condition of forest systems and has a significant
      importance for ecosystem models as a main input. The aim of this study is to
      estimate the percent tree cover of various forest stands in a Mediterranean
      environment based on an empirical relationship between tree coverage and remotely
      sensed data in Goksu Watershed located at the Eastern Mediterranean coast of
      Turkey. A regression tree algorithm was used to simulate spatial fractions of
      Pinus nigra, Cedrus libani, Pinus brutia, Juniperus excelsa and Quercus cerris
      using multi-temporal LANDSAT TM/ETM data as predictor variables and land cover
      information. Two scenes of high resolution GeoEye-1 images were employed for
      training and testing the model. The predictor variables were incorporated in
      addition to biophysical variables estimated from the LANDSAT TM/ETM data.
      Additionally, normalised difference vegetation index (NDVI) was incorporated to
      LANDSAT TM/ETM band settings as a biophysical variable. Stepwise linear
      regression (SLR) was applied for selecting the relevant bands to employ in
      regression tree process. SLR-selected variables produced accurate results in the
      model with a high correlation coefficient of 0.80. The output values ranged from
      0 to 100 %. The different tree species were mapped in 30 m resolution in respect
      to elevation. Percent tree cover map as a final output was derived using LANDSAT
      TM/ETM image over Goksu Watershed and the biophysical variables. The results were
      tested using high spatial resolution GeoEye-1 images. Thus, the combination of
      the RT algorithm and higher resolution data for percent tree cover mapping were
      tested and examined in a complex Mediterranean environment. 

PMID- 25604063
TI  - Waste load allocation in rivers under uncertainty: application of social choice
      procedures.
AB  - In this paper, a waste load allocation model is developed which can incorporate
      uncertainties due to randomness as well as vagueness regarding some variables and
      parameters. A probabilistic water quality index is also presented and used in the
      waste load allocation model. For any discharger of the system, different
      wastewater treatment scenarios are defined. All possible combinations of these
      scenarios make different wastewater treatment alternatives for the system. An
      optimization model having the objectives of minimizing total treatment cost as
      well as water quality violation risk is also developed for finding the optimum
      treatment alternatives. The uncertainty related to the upstream river flow is
      addressed through considering probability distribution functions with fuzzy
      parameters. To deal with fuzzy and random inputs, the fuzzy transformation
      technique and Monte Carlo analysis are respectively used, and for each
      alternative, fuzzy membership function of the violation risk is obtained. The
      optimization model only takes into account the economic and environmental
      objectives and does not specifically consider the stakeholders satisfaction. To
      consider this and help the decision maker choose a final alternative among non
      dominated solutions, three different social choice procedures which focus on
      stakeholders priorities are employed. The applicability and effectiveness of the
      methodology are evaluated by applying it to the Zarjub River in Iran facing
      serious water quality issues. The results indicate that the presented methodology
      can effectively take account of priorities of various decision makers as well as
      economic and environmental considerations, while incorporating multiple forms of
      uncertainties. 

PMID- 25604064
TI  - Career Outcomes of Graduates of R25E Short-Term Cancer Research Training
      Programs.
AB  - The efficacy of short-term cancer research educational programs in meeting its
      immediate goals and long-term cancer research career objectives has not been well
      studied. The purpose of this report is to describe the immediate impact on, and
      the long-term career outcomes of, 499 medical students and graduate students who
      completed the Cancer Research Experiences for Students (CaRES) program at the
      University of Alabama at Birmingham (UAB) from 1999 to 2013. In summer 2014, all
      499 program alumni were located and 96.4 % (481 of 499) agreed to complete a
      longitudinal tracking survey. About 23 % of CaRES alumni (110 of 499) have
      published at least one cancer-related paper. Overall 238 cancer-related papers
      have been published by CaRES alumni, one third of this number being first
      authored publications. Nearly 15 % (71 of 481 respondents) reported that their
      current professional activities include cancer research, primarily clinical
      research and outcomes research. Of these 71 individuals, 27 (38 %) have completed
      their training and 44 (62 %) remain in training. Of all respondents, 58 %
      reported that they administered care to cancer patients and 30 % reported other
      cancer-related professional responsibilities such as working with a health
      department or community group on cancer control activities. Of the 410
      respondents not currently engaged in cancer research, 118 (29 %) stated
      intentions to conduct cancer research in the next few years. Nearly all
      respondents (99.6 %) recommended CaRES to today's students. Challenging short
      term educational cancer research programs for medical students and graduate
      health professional students can help them refine and solidify their career
      plans, with many program alumni choosing cancer research careers.

PMID- 25604065
TI  - Assessing treatment effects in older breast cancer patients: systematic review of
      observational research methods.
AB  - Solid evidence of treatment effects in older women with breast cancer is lacking,
      as they are generally underrepresented in randomized clinical trials on which
      guideline recommendations are based. An alternative way to study treatment
      effects in older patients could be to use data from observational studies.
      However, using appropriate methods in analyzing observational data is a key
      condition in order to draw valid conclusions, as directly comparing treatments
      generally results in biased estimates due to confounding by indication. The aim
      of this systematic review was to investigate the methods that have been used in
      observational studies that assessed the effects of breast cancer treatment on
      survival, breast cancer survival and recurrence in older patients (aged 65 years
      and older). Studies were identified through systematic review of the literature
      published between January 1st 2009 and December 13th 2013 in the PubMed database
      and EMBASe. Finally, 31 studies fulfilled the inclusion criteria. Of these, 22
      studies directly compared two treatments. Fifteen out of these 22 studies
      addressed the problem of confounding by indication, while seven studies did not.
      Nine studies used some form of instrumental variable analysis. In conclusion, the
      vast majority of observational studies that investigate treatment effects in
      older breast cancer patients compared treatments directly. These studies are
      therefore likely to be biased. Observational research will be essential to
      improve treatment and outcome of older breast cancer patients, but the use of
      accurate methods is essential to draw valid conclusions from this type of data.

PMID- 25604066
TI  - Improved metabolites of pharmaceutical ingredient grade Ginkgo biloba and the
      correlated proteomics analysis.
AB  - Ginkgo biloba is an attractive and traditional medicinal plant, and has been
      widely used as a phytomedicine in the prevention and treatment of cardiovascular
      and cerebrovascular diseases. Flavonoids and terpene lactones are the major
      bioactive components of Ginkgo, whereas the ginkgolic acids (GAs) with strong
      allergenic properties are strictly controlled. In this study, we tested the
      content of flavonoids and GAs under ultraviolet-B (UV-B) treatment and performed
      comparative proteomic analyses to determine the differential proteins that occur
      upon UV-B radiation. That might play a crucial role in producing flavonoids and
      GAs. Our phytochemical analyses demonstrated that UV-B irradiation significantly
      increased the content of active flavonoids, and decreased the content of toxic
      GAs. We conducted comparative proteomic analysis of both whole leaf and
      chloroplasts proteins. In total, 27 differential proteins in the whole leaf and
      43 differential proteins in the chloroplast were positively identified and
      functionally annotated. The proteomic data suggested that enhanced UV-B radiation
      exposure activated antioxidants and stress-responsive proteins as well as reduced
      the rate of photosynthesis. We demonstrate that UV-B irradiation pharmaceutically
      improved the metabolic ingredients of Ginkgo, particularly in terms of reducing
      GAs. With high UV absorption properties, and antioxidant activities, the
      flavonoids were likely highly induced as protective molecules following UV-B
      irradiation.

PMID- 25604068
TI  - Duration of symptom and ABCD2 score as predictors of risk of early recurrent
      events after transient ischemic attack: a hospital-based case series study.
AB  - BACKGROUND: The aim of this study was to refine clinical risk factor
      stratification and make an optimal intervention plan to prevent ischemic stroke.
      MATERIAL/METHODS: Clinical data, including diffusion-weighted imaging (DWI)
      findings, were collected in a cohort of hospitalized transient ischemic attack
      (TIA) patients from January 2010 to December 2011. Recurrent cerebrovascular
      events after TIA, including recurrent TIA, minor stroke, and major stroke, were
      identified by face-to-face follow-up. A multivariate, ordinal, logistic
      regression model was used to determine significant predictors of recurrent
      events. RESULTS: Of 106 TIA patients, 24 (22.6%) had recurrent TIA and 20 (18.9%)
      had a stroke within 7 days. Hypertension, dyslipidemia, a history of ischemic
      stroke or TIA, and ABCD2 score were significantly associated with the recurrent
      events after TIA (P<0.001, P=0.02, P<0.001, P=0.02). Hypertension (RR=9.21; 95%
      CI, 3.07-27.61, P<0.001) and duration of symptom (RR=1.10; 95% CI, 1.02-1.17,
      P=0.01) as an item of ABCD2 score were highly predictive of the severity of
      recurrent events, whereas ABCD2 score as a whole (P=0.18) proved to be less
      strongly predictive. CONCLUSIONS: A history of hypertension and long duration of
      symptom independently and significantly predict severe recurrent events after TIA
      within 7 days, but a high ABCD2 score was less strongly predictive of severe
      recurrent events.

PMID- 25604067
TI  - How apoptotic beta-cells direct immune response to tolerance or to autoimmune
      diabetes: a review.
AB  - Type 1 diabetes (T1D) is a metabolic disease that results from the autoimmune
      attack against insulin-producing beta-cells in the pancreatic islets of
      Langerhans. Currently, there is no treatment to restore endogenous insulin
      secretion in patients with autoimmune diabetes. In the last years, the
      development of new therapies to induce long-term tolerance has been an important
      medical health challenge. Apoptosis is a physiological mechanism that contributes
      to the maintenance of immune tolerance. Apoptotic cells are a source of
      autoantigens that induce tolerance after their removal by antigen presenting
      cells (APCs) through a process called efferocytosis. Efferocytosis will not cause
      maturation in dendritic cells, one of the most powerful APCs, and this process
      could induce tolerance rather than autoimmunity. However, failure of this
      mechanism due to an increase in the rate of beta-cells apoptosis and/or defects
      in efferocytosis results in activation of APCs, contributing to inflammation and
      to the loss of tolerance to self. In fact, T1D and other autoimmune diseases are
      associated to enhanced apoptosis of target cells and defective apoptotic cell
      clearance. Although further research is needed, the clinical relevance of
      immunotherapies based on apoptosis could prove to be very important, as it has
      translational potential in situations that require the reestablishment of
      immunological tolerance, such as autoimmune diseases. This review summarizes the
      effects of apoptosis of beta-cells towards autoimmunity or tolerance and its
      application in the field of emerging immunotherapies. 

PMID- 25604069
TI  - Analysis of the essentiality of ROM2 genes in the pathogenic yeasts Candida
      glabrata and Candida albicans using temperature-sensitive mutants.
AB  - AIMS: To analyse the essentiality of the ROM2 genes originating from the
      pathogenic yeasts Candida glabrata and Candida albicans by using temperature
      sensitive (ts) mutants. METHODS AND RESULTS: Based on the general concepts that
      ts mutations are generated by virtue of point mutation within essential genes, we
      have previously established a novel method (termed 'ETS system' for screening and
      identification of essential genes using ts mutants of C. glabrata). According to
      this ETS system, the present study successfully identified a putative C. glabrata
      ROM2 homologue as an essential gene that complements its point mutation (Cys
      1275/Tyr substitution). The C. albicans ROM2 mutant (Cys-1281/Tyr), constructed
      patterned after this point mutation, also displayed ts phenotype. Both ts mutants
      recovered colony-forming ability, with concomitant suppression of lysis
      phenotype, at the elevated temperature in the presence of 1 mol l(-1) sorbitol as
      an osmotic stabilizer. Sequence alignment revealed that human genome possesses
      relatively low homology against Rom2 homologues, which are highly conserved among
      yeast species. CONCLUSIONS: ROM2 genes of C. glabrata and C. albicans are
      essential for viability, probably involved in cell wall integrity. SIGNIFICANCE
      AND IMPACT OF THE STUDY: ROM2 genes essential for both Candida species may be a
      potentially useful antifungal targets from chemotherapeutic viewpoint.

PMID- 25604070
TI  - [Interventional stroke prophylaxis : endocardial and epicardial left atrial
      appendage closure].
AB  - Atrial fibrillation (AF) is currently one of the major causes of ischemic stroke
      with an estimated stroke risk of 5% per year. Oral anticoagulation is an
      effective treatment for the reduction of stroke risk in patients with AF but is
      also associated with an increased risk of bleeding. In patients with AF it has
      been shown that left atrial thrombi can be identified within the left atrial
      appendage (LAA) in more than 90% of cases. On the basis of these findings LAA
      closure devices have been developed as an alternative to oral anticoagulation.
      Besides endocardial LAA occluders, such as the WATCHMANTM and AMPLATZERTM
      devices, an epicardial LAA occluder (LARIATTM) has recently been introduced. The
      following review introduces the various endocardial and epicardial LAA closure
      devices and assesses the indications, management, advantages and disadvantages of
      the two approaches according to the current literature. 

PMID- 25604071
TI  - [Prevalence and risk factors of atrial fibrillation in Germany : data from the
      Gutenberg Health Study].
AB  - Atrial fibrillation (AF) is a disease with increasing clinical and public health
      importance. We describe the prevalence of AF, the current distribution of AF risk
      factors and their importance in a general population. The distribution of AF risk
      factors and the medicinal treatment were determined among 10,000 individuals in
      the population-based Gutenberg Health Study (median age 56 years and 49% women).
      Individuals with AF (n=309, 3.1%) had a higher median age (67 years) and
      significantly more risk factors. A large percentage of individuals with AF were
      taking antithrombotic medication (84% with a CHAD2DS2-VASc score of >=3).
      Multiple logistic regression analysis showed that male gender (odds ratio, OR
      2.07, 95% CI: 1.59-2.71), age (OR 1.09, 95% CI: 1.07-1.11), body mass index (OR
      1.04, 95% CI: 1.02-1.07), prevalent cardiovascular disease (OR 3.06, 95% CI: 2.26
      4.11) and heart failure (OR 3.11, 95% CI: 1.92-4.97) were the strongest
      predictors of AF. The full model explained 18% (Nagelkerke's determination
      coefficient R(2)) of the variation in AF prevalence. The addition of
      echocardiographic variables in a subgroup analysis with 5.000 participants
      increased the explained variation to 23%. AF is a common disease in the general
      population. Important risk factors for AF, apart from age and male gender, were
      cardiovascular disease, in particular heart failure, hypertension and increased
      body mass index. Awareness for AF in the population and medical community needs
      to be improved. 

PMID- 25604073
TI  - Oxidation-initiated myosin subfragment cross-linking and structural instability
      differences between white and red muscle fiber types.
AB  - Both white and red muscles are commonly used in meat processing, and protein
      cross-linking, which may be affected by oxidants, is a key factor affecting the
      product quality. In this study, myofibrillar proteins (MPs) extracted from
      postrigor chicken Pectoralis major (PM, predominantly white) and Gastrocnemius
      (GN, predominantly red) muscles were subjected to a *OH-oxidizing system (10 MUM
      FeCl3 , 0.1 mM ascorbic acid, with 0, 5, 10, or 20 mM H2 O2 ) at pH 6.2, 4 
      degrees C for 18 h. The solubility of nonoxidized (control) PM MPs (63%) was
      higher than that of control GN MPs (41%). After oxidation with *OH generated at 5
      mM H2 O2 , protein solubility decreased by 46% and 21% for PM and GN,
      respectively, due to aggregation. Chemical and electrophoretic analyses indicated
      H2 O2 -dose-dependent losses of sulfhydryls and the concomitant formation of
      disulfides which were more pronounced in PM protein samples. Oxidation favored
      cross-linking of myosin rod or tail in PM MPs compared to an equal susceptibility
      of myosin subfragment-1 (s-1) and rod to *OH in GN MPs. Both Ca- and K-ATPase
      activities in GN myosin were more sensitive to *OH than their PM counterparts,
      indicating a less stable s-1 region of GN myosin to oxidation. The uncoiling of
      rods from PM myosin was more rapid than that in GN myosin during heating.
      Oxidation induced cross-linking via disulfide bonds hindered the unfolding of
      rod, particularly in PM myosin. These data revealed the molecular events that
      underscore the necessity of meat processing and formulation control based on
      muscle fiber types. 

PMID- 25604072
TI  - In vitro evaluation of a novel non-mulberry silk scaffold for use in tendon
      regeneration.
AB  - Tearing of the rotator cuff tendon in the shoulder is a significant clinical
      problem, with large/full-thickness tears present in ~22% of the general
      population and recurrent tear rates postarthroscopic repair being quoted as high
      as 94%. Tissue-engineered biomaterials are increasingly being investigated as a
      means to augment rotator cuff repairs, with the aim of inducing host cell
      responses to increase tendon tissue regeneration. Silk-derived materials are of
      particular interest due to the high availability, mechanical strength, and
      biocompatibility of silks. In this study, Spidrex((r)), a novel knitted, non
      mulberry silk fibroin scaffold was evaluated in vitro for its potential to
      improve tendon regeneration. Spidrex was compared with a knitted Bombyx mori silk
      scaffold, a 3D collagen gel and Fiberwire((r)) suture material. Primary human and
      rat tenocytes successfully adhered to Spidrex and significantly increased in
      number over a 14 day period (p<0.05), as demonstrated by fluorescent calcein-AM
      staining and alamarBlue((r)) assays. A similar growth pattern was observed with
      human tenocytes cultured on the B. mori scaffold. Morphologically, human
      tenocytes elongated along the silk fibers of Spidrex, assuming a tenocytic cell
      shape, and were less circular with a higher aspect ratio compared with human
      tenocytes cultured on the B. mori silk scaffold and within the collagen gel
      (p<0.05). Gene expression analysis by real-time PCR showed that rat tenocytes
      cultured on Spidrex had increased expression of tenocyte-related genes such as
      fibromodullin, scleraxis, and tenomodulin (p<0.05). Expression of genes that
      indicate transdifferentiation toward a chondrocytic or osteoblastic lineage were
      significantly lower in tenocytes cultured on Spidrex in comparison to the
      collagen gel (p<0.05). Immunogenicity assessment by the maturation of and
      cytokine release from primary human dendritic cells demonstrated that Spidrex
      enhanced dendritic cell maturation in a similar manner to the clinically used
      suture material Fiberwire, and significantly upregulated the release of
      proinflammatory cytokines (p<0.05). This suggests that Spidrex may induce an
      early immune response postimplantation. While further work is required to
      determine what effect this immune response has on the tendon healing process, our
      in vitro data suggests that Spidrex may have the cytocompatibility and
      bioactivity required to support tendon regeneration in vivo. 

PMID- 25604074
TI  - Silage or fresh by-product of peach palm as roughage in the feeding of lambs.
AB  - The objective of this study was to evaluate intake and apparent digestibility of
      agro-industrial by-product of peach palm in diets for lambs. Twenty castrated,
      crossbred Santa Ines lambs, with average age of 150 days and body weight of 22.4
      +/- 3.4 kg, were distributed in a completely randomized design with four
      experimental diets composed of the following: fresh by-product of peach palm
      enriched with urea + ammonia sulfate (FU); fresh peach palm by-product +
      concentrate (FP); silage of peach palm by-product + concentrate (SP); and silage
      of peach palm by-product enriched with 15% of cornmeal + concentrate (SPC).
      Intake was recorded daily, and the digestibility coefficients were estimated with
      the internal marker indigestible acid detergent fiber (iADF). Diet FU resulted in
      the lowest intake and digestibility of the nutrients evaluated. Animals receiving
      diet FP showed higher intakes of dry matter (DM), organic matter (OM), crude
      protein (CP), neutral detergent fiber (NDF), total digestible nutrients (TDN),
      and digestible energy (DE) in relation to animals fed diets SP and SPC. Diets SP
      and SPC showed higher coefficients of digestibility of DM, OM, CP, and NDF than
      diet FP. Diet SP reduced the intakes of DM, OM, ether extract (EE), non-fibrous
      carbohydrate (NFC), TDN, and DE and the digestibility coefficients of DM, OM, and
      NFC as compared with diet SPC. Feedlot lambs fed a diet with fresh peach palm by
      product + concentrate (diet FP) have higher nutrient intake.

PMID- 25604075
TI  - Double balloon enteroscopy for removal of retained video capsules.

PMID- 25604076
TI  - Investigating the stress attenuating potential of furosemide in immobilization
      and electric foot-shock stress models in mice.
AB  - The present study was designed to investigate the antistress effect of furosemide
      (sodium potassium chloride co-transporter inhibitor) in immobilization and foot
      shock stress-induced behavioral alterations in the mice. Acute stress was induced
      in Swiss albino mice either by applying electric foot shocks of 0.6-mA intensity
      of 1-s duration with 30-s inter-shock interval for 1 h or immobilizing for 150
      min. The acute stress-induced behavioral changes were assessed by using
      actophotometer, hole board, open-field, and social interaction tests.
      Biochemically, the corticosterone levels were estimated in the serum as a
      biomarker of hypothalamus-pituitary-adrenal (HPA) axis. Acute stress resulted in
      the development of behavioral alterations and elevation of the corticosterone
      levels. Intraperitoneal administration of furosemide (25 and 50 mg/kg)
      significantly attenuated immobilization and foot-shock stress-induced behavioral
      changes along with normalization of the corticosterone levels. It may be
      concluded that furosemide produces beneficial effects in reestablishing the
      behavioral and biochemical alterations in immobilization and foot-shock-induced
      acute stress in mice. 

PMID- 25604077
TI  - Potencies and unblocking kinetic properties of antagonists at recombinant human
      NMDA receptors in a Xenopus oocytes model.
AB  - N-methyl-D-aspartate (NMDA) receptor channels are implicated in a wide range of
      physiological and pathophysiological processes, and a large number of
      pharmacological agents have been introduced that target the receptor via diverse
      mechanisms of action. Amongst others, subunit selectivity (in particular for the
      NR2B receptor subunit) and rapid unblocking kinetics have been put forward as
      favourable pharmacological properties of NMDA receptor-targeting drugs. Here, we
      describe a pharmacological characterization of human recombinant NMDA receptors
      expressed in Xenopus oocytes in an electrophysiological set-up. Using this
      approach, we compare inhibitor potencies of several known NMDA receptor ligands
      as well as unblocking kinetic properties of selected compounds. All compounds
      tested had similar potencies at receptors containing NR2A or NR2B receptors with
      the exception of traxoprodil, which was selective for NR2B. The rank order of
      potency was (+)MK-801 > phencyclidine (PCP) ~ traxoprodil > memantine ~ ketamine
      > duloxetine. In line with its proposed rapid dissociation properties, the
      relatively well-tolerated drug memantine exhibits markedly faster unblocking than
      ketamine and PCP, similar to the low-affinity compound, duloxetine.
      Electrophysiological recording in Xenopus oocytes thus allows a relatively
      convenient comparison of key pharmacological parameters at recombinant human NMDA
      receptors. 

PMID- 25604079
TI  - The PUFA-enriched fatty acid profiles of some frozen bison from the early
      Holocene found in the Siberian permafrost.
AB  - Knowledge concerning the availability of n-3 fatty acids for humans in
      prehistoric times is highly relevant in order to draw useful conclusions on the
      healthy dietary habits for present-day humans. To this end, we have analysed fat
      from several frozen bison found in the permafrost of Siberia (Russia). A total of
      3 bison were included in this study, all them very close to the early Holocene
      (8,000; 8,200; and 9,300 years BP). All samples were analysed by gas-liquid
      chromatography-mass spectrometry (GLC-MS) and GLC flame-ionization detection (GLC
      FID). Fat samples from two bison showed two well-differenced areas, i.e. brown
      and white, the latter being saturated fatty acid enriched, corresponding to an
      intermediate stage of adipocere formation, while the brown ones yielded alpha
      linolenic acid in higher percentages than found in present-day bison. As
      demonstrated in this work, the subcutaneous fat of bison consumed by Mesolithic
      hunters contained amounts of n-3 fatty acids in higher quantities than those
      found in current bison; thus, the subcutaneous fat of bison could have
      contributed to meet today's recommended daily intake of essential fatty acids for
      good health in the Mesolithic to a greater extent than previously thought. 

PMID- 25604078
TI  - Targeting protein kinase C subtypes in pancreatic cancer.
AB  - In preclinical studies, protein kinase C (PKC) enzymes have been implicated in
      regulating many aspects of pancreatic cancer development and progression.
      However, clinical Phase I or Phase II trials with compounds targeting classical
      PKC isoforms were not successful. Recent studies implicate that mainly atypical
      and novel PKC enzymes regulate oncogenic signaling pathways in pancreatic cancer.
      Members of these two subgroups converge signaling induced by mutant Kras, growth
      factors and inflammatory cytokines. Different approaches for the development of
      inhibitors for atypical PKC and novel PKC have been described; and new compounds
      include allosteric inhibitors and inhibitors that block ATP binding.

PMID- 25604081
TI  - Comparison of the chemical composition of normal enamel from exfoliated primary
      teeth and teeth affected with early childhood caries: an in vitro study.
AB  - AIM: The aim of this study was to compare the chemical composition of enamel from
      teeth with early childhood caries (unaffected fragments) and from healthy primary
      teeth. DESIGN: Forty exfoliated primary teeth (Group I) and 40 teeth affected
      with ECC (Group II) were collected. Unaffected enamel from the ECC group was
      sampled. Elemental analysis was carried out with energy-dispersive X-ray
      spectroscopy (EDS), following which the same tooth samples were subjected to
      amino acid analysis by high-performance liquid chromatography (HPLC). RESULTS:
      Statistically significant differences were observed in the percentage of
      phosphorus (P) and the Ca/P ratios between the two groups in the elemental
      analysis. Amino acid analysis revealed no significant difference in the amino
      acid profile and the quantity of amino acid or protein content between the two
      groups. CONCLUSIONS: This study showed significant differences in the P content
      and Ca/P ratio between the enamel from teeth with ECC and in that from healthy
      primary teeth. These findings indicate that differences in the composition of
      enamel could be a risk factor for ECC.

PMID- 25604080
TI  - Methotrexate Restores Regulatory T Cell Function Through Demethylation of the
      FoxP3 Upstream Enhancer in Patients With Rheumatoid Arthritis.
AB  - OBJECTIVE: We have previously shown, in a cohort of untreated rheumatoid
      arthritis (RA) patients, that the suppressive function of Treg cells is
      defective. However, other studies in cohorts of patients with established RA have
      shown that Treg cell function is normal. We hypothesized that treatment may
      restore Treg cell function and lead to reduced disease activity. The aim of this
      study was to investigate whether treatment with methotrexate (MTX) can result in
      epigenetic changes that lead to restoration of the Treg cell suppressive function
      in RA. METHODS: Peripheral blood samples from RA patients were assessed using (3)
      H-thymidine incorporation to measure Treg cell suppression of T cell
      proliferation, and by enzyme-linked immunosorbent assay to determine Treg cell
      suppression of interferon-gamma production. CTLA-4 and FoxP3 expression was
      measured by flow cytometry and quantitative polymerase chain reaction (qPCR) in
      Treg cells from healthy individuals and RA patients. CD4+ T cells isolated from
      healthy individuals were cultured with interleukin-2 (IL-2), IL-6, and tumor
      necrosis factor alpha in the presence or absence of MTX, and FoxP3 expression was
      determined using qPCR and flow cytometry. Methylation of the FOXP3 upstream
      enhancer was analyzed by bisulfite sequencing PCR. RESULTS: Defective Treg cell
      function was observed only in RA patients who had not been treated with MTX,
      whereas Treg cells from MTX-exposed RA patients had restored suppressive
      function. This restored suppression was associated with increased expression of
      FoxP3 and CTLA-4 in Treg cells. Bisulfite sequencing PCR of Treg cells cultured
      in MTX revealed a significant reduction in methylation of the FOXP3 upstream
      enhancer. CONCLUSION: This study identifies a novel mechanism of action of MTX,
      in which treatment of RA patients with MTX restores defective Treg cell function
      through demethylation of the FOXP3 locus, leading to a subsequent increase in
      FoxP3 and CTLA-4 expression.

PMID- 25604082
TI  - Genetic associations of the interleukin locus at 1q32.1 with clinical outcomes of
      cutaneous melanoma.
AB  - BACKGROUND: Due to high melanoma immunogenicity, germline genetic variants in
      immune pathways have been studied for association with melanoma prognosis.
      However, limited candidate selection, inadequate power, or lack of independent
      validation have hampered the reproducibility of these prior findings, preventing
      personalised clinical applicability in melanoma prognostication. Our objective
      was to assess the prognostic utility of genetic variants in immunomodulatory
      pathways for prediction of melanoma clinical outcomes. METHODS: We genotyped 72
      tag single nucleotide polymorphisms (SNPs) in 44 immunomodulatory genes in a
      population sample of 1022 melanoma patients and performed Cox regression analysis
      to test the association between SNPs and melanoma recurrence-free (RFS) and
      overall survival (OS). We have further investigated the most significant
      associations using a fine mapping strategy and followed with functional analyses
      in CD4+ T cells in a subset of 75 melanoma patients. RESULTS: The most
      significant associations were found with melanoma OS for rs3024493 in IL10 at
      chromosome 1q32.1 (heterozygous HR 0.58, 95% CI 0.39 to 0.86; p=0.0006), a
      variant previously shown to be linked with autoimmune conditions. Multiple
      additional SNPs at 1q32.1 were also nominally associated with OS confirming at
      least two independent association signals in this locus. In addition, we found
      rs3024493 associated with the downregulation of interleukin 10 (IL10) secretion
      in CD4+ T cells. CONCLUSIONS: We discovered novel associations of IL10 with
      melanoma survival at 1q32.1, suggesting this locus should be considered as a
      novel melanoma prognostic biomarker with potential for aiding melanoma patient
      management. Our findings also provide further support for an alternative role of
      IL10 in stimulation of anti-tumour immune response.

PMID- 25604083
TI  - Copy number variation of two separate regulatory regions upstream of SOX9 causes
      isolated 46,XY or 46,XX disorder of sex development.
AB  - BACKGROUND: SOX9 mutations cause the skeletal malformation syndrome campomelic
      dysplasia in combination with XY sex reversal. Studies in mice indicate that SOX9
      acts as a testis-inducing transcription factor downstream of SRY, triggering
      Sertoli cell and testis differentiation. An SRY-dependent testis-specific
      enhancer for Sox9 has been identified only in mice. A previous study has
      implicated copy number variations (CNVs) of a 78 kb region 517-595 kb upstream of
      SOX9 in the aetiology of both 46,XY and 46,XX disorders of sex development (DSD).
      We wanted to better define this region for both disorders. RESULTS: By CNV
      analysis, we identified SOX9 upstream duplications in three cases of SRY-negative
      46,XX DSD, which together with previously reported duplications define a 68 kb
      region, 516-584 kb upstream of SOX9, designated XXSR (XX sex reversal region).
      More importantly, we identified heterozygous deletions in four families with SRY
      positive 46,XY DSD without skeletal phenotype, which define a 32.5 kb interval
      607.1-639.6 kb upstream of SOX9, designated XY sex reversal region (XYSR). To
      localise the suspected testis-specific enhancer, XYSR subfragments were tested in
      cell transfection and transgenic experiments. While transgenic experiments
      remained inconclusive, a 1.9 kb SRY-responsive subfragment drove expression
      specifically in Sertoli-like cells. CONCLUSIONS: Our results indicate that
      isolated 46,XY and 46,XX DSD can be assigned to two separate regulatory regions,
      XYSR and XXSR, far upstream of SOX9. The 1.9 kb SRY-responsive subfragment from
      the XYSR might constitute the core of the Sertoli-cell enhancer of human SOX9,
      representing the so far missing link in the genetic cascade of male sex
      determination.

PMID- 25604084
TI  - Mutations in COA3 cause isolated complex IV deficiency associated with
      neuropathy, exercise intolerance, obesity, and short stature.
AB  - BACKGROUND: We investigated a subject with an isolated cytochrome c oxidase (COX)
      deficiency presenting with an unusual phenotype characterised by neuropathy,
      exercise intolerance, obesity, and short stature. METHODS AND RESULTS: Blue
      native polyacrylamide gel electrophoresis (BN-PAGE) analysis showed an almost
      complete lack of COX assembly in subject fibroblasts, consistent with the very
      low enzymatic activity, and pulse-labelling mitochondrial translation experiments
      showed a specific decrease in synthesis of the COX1 subunit, the core catalytic
      subunit that nucleates assembly of the holoenzyme. Whole exome sequencing
      identified compound heterozygous mutations (c.199dupC, c.215A>G) in COA3, a small
      inner membrane COX assembly factor, resulting in a pronounced decrease in the
      steady-state levels of COA3 protein. Retroviral expression of a wild-type COA3
      cDNA completely rescued the COX assembly and mitochondrial translation defects,
      confirming the pathogenicity of the mutations, and resulted in increased steady
      state levels of COX1 in control cells, demonstrating a role for COA3 in the
      stabilisation of this subunit. COA3 exists in an early COX assembly complex that
      contains COX1 and other COX assembly factors including COX14 (C12orf62), another
      single pass transmembrane protein that also plays a role in coupling COX1
      synthesis with holoenzyme assembly. Immunoblot analysis showed that COX14 was
      undetectable in COA3 subject fibroblasts, and that COA3 was undetectable in
      fibroblasts from a COX14 subject, demonstrating the interdependence of these two
      COX assembly factors. CONCLUSIONS: The mild clinical course in this patient
      contrasts with nearly all other cases of severe COX assembly defects that are
      usually fatal early in life, and underscores the marked tissue-specific
      involvement in mitochondrial diseases.

PMID- 25604086
TI  - The role of carboxyhemoglobin measured with CO-oximetry in the detection of
      hemolysis in newborns with ABO alloimmunization.
AB  - OBJECTIVES: To evaluate carboxyhemoglobin (COHb) values measured with a CO
      oximeter (Roche-cobas b 221) in jaundiced newborns with or without hemolysis and
      healthy controls in order to assess whether COHb measurement determined with a CO
      oximeter could be used as an indicator of hemolysis in newborns with ABO
      alloimmunization. METHODS: A total of 86 term newborn infants were prospectively
      studied. The study cohort consisted of three subgroups: 18 infants with ABO HDN,
      21 infants with hyperbilirubinemia without hemolytic disease who required
      phototherapy, and 47 healthy controls. The COHb, bilirubin, and Hb levels were
      measured. RESULTS: The three subgroups did not differ significantly with respect
      to birth weight, gestational age, gender, Apgar score, or mode of delivery. The
      ABO HDN infants had significantly higher COHb values than the healthy controls
      (median 2.4% versus 1.3%, p < 0.0005) and the group with hyperbilirubinemia
      without hemolytic disease (median 2.4% versus 1.3%, p < 0.0005), although the
      infants with hyperbilirubinemia without hemolytic disease did not have
      significantly higher COHb values compared with the healthy controls. The cut-off
      value of 1.7% COHb had 72% sensitivity and 97% specificity for confirming
      hemolysis in ABO alloimmunization. CONCLUSIONS: Our data show that COHb values
      determined with CO-oximeters are higher in newborns with hemolysis than in those
      without hemolysis. COHb measured with CO-oximeters could be used to confirm
      hemolysis in infants with ABO alloimmunization.

PMID- 25604085
TI  - Elevated risk of thrombophilia in agenesis of the vena cava as a factor for deep
      vein thrombosis.
AB  - BACKGROUND: Congenital absence of the inferior vena cava (AIVC) is a rare
      malformation which may be associated with an increased risk for deep vein
      thrombosis (DVT). However, the role of thrombophilia in AIVC and DVT is unknown.
      METHODS: Between 1982 and 2013 41 patients (12 female, 29 male, mean age 28 S.D.
      11 years) were detected at the University of Dusseldorf, Germany, with AIVC.
      Based on medical history, clinical examination, imaging and coagulation studies,
      we performed on this collective a risk characterisation. Extensive literature
      research added further 123 published cases during 1993 and 2013. AIVC-patients
      were compared with iliocaval DVT-patients without AIVC (n = 168) treated during
      the same period in our clinic (90 female, 78 male, mean age 38 S.D. 17 years).
      RESULTS: In contrast to classical DVT younger men were more often affected.
      Factor-V-Leiden-mutation, 5,10-methylenetetrahydrofolate reductase (MTHFR)
      polymorphism and hyperhomocysteinemia individually are associated with an
      increased risk of DVT in patients with AIVC. Aplasia/hypoplasia of the right or
      left kidney is also associated with IVCA. CONCLUSIONS: AIVC should be considered
      in young patients who present with DVT involving the vena cava. Analysis of
      publications with AIVC and our patients yielded a typical spectrum of AIVC
      associated DVT characteristics: AIVC occurs in young male adults, is revealed by
      proximal DVT, not necessarily accused by precipitating factors like
      immobilisation, and is mostly located bilateral. Hereditary coagulation
      abnormalities seem to be more often a contributing factor for DVT in AIVC.

PMID- 25604088
TI  - Cerebral and somatic NIRS-determined oxygenation in IUGR preterm infants during
      transition.
AB  - BACKGROUND: Fetal growth restriction (intra-uterine growth restriction [IUGR])
      has a considerable impact on perinatal morbidity. Preterm IUGR infants are prone
      to impaired intestine function. Near-infrared spectroscopy (NIRS) has been used
      to monitor oxygenation status of the brain and of the intestine. PATIENTS AND
      METHODS: We conducted a prospective case-control study at our NICU in 20 preterm
      infants of whom 10 infants complicated by compared with 10 non-IUGR preterm
      infants. Splanchnic and cerebral regional oximetry values were measured with
      NIRS. Three hours of consecutive recordings were performed in the first 24 h of
      life, T0, and during the transitional period, T1. The cerebral/splanchnic
      oxygenation ratio, CSOR, (cerebral regional saturations [rScO2]/splanchnic
      regional saturations [rSsO2]) was also calculated. RESULTS: Both in the IUGR and
      the non-IUGR infants, at T0 and T1 monitoring time-points, the rSO2 values were
      higher in the cerebral district when compared to those of the splanchnic area.
      Comparison of the NIRS parameters between the IUGR and non-IUGR infants at T0
      showed no difference in rScO2, while rSsO2 was significantly lower in the IUGR
      group. At T1, rScO2 was significantly lower and rSsO2 higher in the IUGR group.
      CONCLUSIONS: Cerebral/splanchnic vascular adaptation of IUGR infants to the extra
      uterine environment is characterized by a postnatal persistence of the brain
      sparing effect with reperfusion in the transitional period.

PMID- 25604087
TI  - Expression of DAB2IP in human trophoblast and its role in trophoblast invasion.
AB  - OBJECTIVE: DAB2IP is a growth inhibitor present in many types of cancer cells and
      is associated with epigenetic regulations controlling tumor development. The
      primary objective of this study is to determine whether DAB2IP participates in
      the invasion and migration of trophoblasts during placental development. METHODS:
      The expressions of DAB2IP in human placentas (10 villi, 18 term placentas and 20
      pre-eclampsia placentas) were determined by immunohistochemistry, Western
      blotting and quantitative RT-PCR. HTR8/SVneo cells were treated with hypoxia
      reoxygenation (H/R) to test how DAB2IP expression would affect the invasion and
      migration of trophoblasts. JEG-3 andHTR8/SVneo cells were treated with 5-aza-2
      deoxycytidine (5-aza-dC) to study the role of DAB2IP promoter methylation in
      trophoblasts. RESULTS: DAB2IP was strongly expressed in human villi and
      extravillous trophoblasts as well as in HTR8/SVneo cells, but not in pre
      eclampsia placentas. DAB2IP expression increased after H/R treatment, but the
      invasive and migratory abilities of trophoblasts were reduced. DAB2IP expression
      in JEG-3 cells also increased after treatment with 5-aza-dC. CONCLUSIONS: These
      findings strongly suggest that DAB2IP is an important negative regulator at the
      maternal-fetal interface during early pregnancy. Excessive oxidative stress can
      increase DAB2IP expression in trophoblasts. The mechanism of DNA methylation may
      involve in its function during the development of pathologic pregnancy.

PMID- 25604089
TI  - Left atrial appendage occlusion for stroke prevention in atrial fibrillation:
      multicentre experience with the AMPLATZER Cardiac Plug.
AB  - AIMS: To investigate the safety, feasibility, and efficacy of left atrial
      appendage occlusion (LAAO) with the AMPLATZER Cardiac Plug (ACP) for stroke
      prevention in patients with atrial fibrillation (AF). METHODS AND RESULTS: Data
      from consecutive patients treated in 22 centres were collected. A total of 1,047
      patients were included in the study. Procedural success was 97.3%. There were 52
      (4.97%) periprocedural major adverse events. Follow-up was complete in
      1,001/1,019 (98.2%) of successfully implanted patients (average 13 months, total
      1,349 patient-years). One-year all-cause mortality was 4.2%. No death at follow
      up was reported as device-related. There were nine strokes (0.9%) and nine
      transient ischaemic attacks (0.9%) during follow-up. The annual rate of systemic
      thromboembolism was 2.3% (31/1,349 patient-years), which is a 59% risk reduction.
      There were 15 major bleedings (1.5%) during follow-up. The annual rate of major
      bleeding was 2.1% (28/1,349 patient-years), which is a 61% risk reduction.
      Patients with single LAAO on aspirin monotherapy or no therapy and longer follow
      up had fewer cerebral and fewer bleeding events. CONCLUSIONS: In this multicentre
      study, LAAO with the ACP showed high procedural success and a favourable outcome
      for the prevention of AF-related thromboembolism. Modification in antithrombotic
      therapy after LAAO may result in reduction of bleeding events.

PMID- 25604091
TI  - Remodeling of host phosphatidylcholine by Chlamydia acyltransferase is regulated
      by acyl-CoA binding protein ACBD6 associated with lipid droplets.
AB  - The bacterial human pathogen Chlamydia trachomatis invades cells as an infectious
      elementary body (EB). The EB is internalized into a vacuole that is hidden from
      the host defense mechanism, and is modified to sustain the development of the
      replicative reticulate body (RB). Inside this parasitophorous compartment, called
      the inclusion, the pathogen survives supported by an active exchange of nutrients
      and proteins with the host cell. We show that host lipids are scavenged and
      modified into bacterial-specific lipids by the action of a shared human-bacterial
      acylation mechanism. The bacterial acylating enzymes for the essential lipids 1
      acyl-sn-glycerol 3-phosphate and 1-acyl-sn-phosphatidylcholine were identified as
      CT453 and CT775, respectively. Bacterial CT775 was found to be associated with
      lipid droplets (LDs). During the development of C. trachomatis, the human acyl
      CoA carrier hACBD6 was recruited to cytosolic LDs and translocated into the
      inclusion. hACBD6 protein modulated the activity of CT775 in an acyl-CoA
      dependent fashion and sustained the activity of the bacterial acyltransferase by
      buffering the concentration of acyl-CoAs. We propose that disruption of the
      binding activity of the acyl-CoA carrier might represent a new drug-target to
      prevent growth of C. trachomatis.

PMID- 25604090
TI  - Tools for teen moms to reduce infant obesity: a randomized clinical trial.
AB  - BACKGROUND: Unhealthy infant feeding practices, such as a combination of formula
      feeding and early introduction of solids may lead to rapid or excessive weight
      gain in early infancy. Adolescent mothers' feeding behaviors are most directly
      related to infant weight gain in the first year of life. Compared to adult
      mothers, adolescent mothers are less knowledgeable, less responsive, more
      controlling, and less skilled in infant feeding, which interferes with infants'
      healthy growth. The Tools for Teen Moms trial aims to compare the effect of a
      social media intervention for low-income adolescent, first-time mothers of
      infants 2 months of age or younger, versus standard care on infant weight,
      maternal responsiveness, and feeding style and practices. The intervention is
      conducted during the infant's first four months of life to promote healthy
      transition to solids during their first year. Tools for Teen Moms is an
      intervention delivered via a social media platform that actively engages and
      coaches low-income adolescent mothers in infant-centered feeding to reduce
      rapid/excessive infant weight gain in the first six months of life.
      METHODS/DESIGN: We describe our study protocol for a randomized control trial
      with an anticipated sample of 100 low-income African- American and Caucasian
      adolescent, first-time mothers of infants. Participants are recruited through
      Maternal-Infant Health Programs in four counties in Michigan, USA. Participants
      are randomly assigned to the intervention or the control group. The intervention
      provides infant feeding information to mothers via a web-based application, and
      includes daily behavioral challenges, text message reminders, discussion forums,
      and website information as a comprehensive social media strategy over 6 weeks.
      Participants continue to receive usual care during the intervention. Main
      maternal outcomes include: (a) maternal responsiveness, (b) feeding style, and
      (c) feeding practices. The primary infant outcome is infant weight. Data
      collection occurs at baseline, and when the baby is 3 and 6 months old.
      DISCUSSION: Expected outcomes will address the effectiveness of the social media
      intervention in helping teen mothers develop healthy infant feeding practices
      that contribute to reducing the risk of early onset childhood obesity. TRIAL
      REGISTRATION: Clinical Trials.Gov NCT02244424, June 24, 2014.

PMID- 25604092
TI  - Adolescents' internalizing and externalizing problems predict their affect
      specific HPA and HPG axes reactivity.
AB  - We examined psychopathology-neuroendocrine associations in relation to the
      transition into adolescence within a developmental framework that acknowledged
      the interdependence of the HPA and HPG hormone systems in the regulation of
      responses to everyday affective contexts. Saliva samples were collected during
      anxiety and anger inductions from 51 young adolescents (M 13.47, SD = .60 years)
      to evaluate cortisol, DHEA, and testosterone responses. Internalizing and
      externalizing problems were assessed at pre-adolescence (M = 9.27, SD = .58
      years) while youths were in elementary school and concurrently with hormones in
      early adolescence. Externalizing problems from elementary school predicted
      adolescents' reduced DHEA reactivity during anxiety induction. Follow up analyses
      simultaneously examining the contributions of elementary school and adolescent
      problems showed a trend suggesting that youths with higher levels of
      internalizing problems during elementary school eventuated in a profile of
      heightened DHEA reactivity as adolescents undergoing anxiety induction. For both
      the anxiety and the anger inductions, it was normative for DHEA and testosterone
      to be positively coupled. Adolescents with high externalizing problems but low
      internalizing problems marshaled dual axes co-activation during anger induction
      in the form of positive cortisol-testosterone coupling. This is some of the first
      evidence suggesting affective context determines whether dual axes coupling is
      reflective of normative or problematic functioning in adolescence.

PMID- 25604094
TI  - Guideline-concordant lung cancer care and associated health outcomes among
      elderly patients in the United States.
AB  - OBJECTIVES: In the United States (US), the elderly carry a disproportionate
      burden of lung cancer. Although evidence-based guidelines for lung cancer care
      have been published, lack of high quality care still remains a concern among the
      elderly. This study comprehensively evaluates the variations in guideline
      concordant lung cancer care among elderly in the US. MATERIALS AND METHODS: Using
      the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2002
      2007), we identified elderly patients (aged >=65 years) with lung cancer (n =
      42,323) and categorized them by receipt of guideline-concordant care, using
      evidence-based guidelines from the American College of Chest Physicians. A
      hierarchical generalized logistic model was constructed to identify variables
      associated with receipt of guideline-concordant care. Kaplan-Meier analysis and
      Log Rank test were used for estimation and comparison of the three-year survival.
      Multivariate Cox proportional hazards model was constructed to estimate lung
      cancer mortality risk associated with receipt of guideline-discordant care.
      RESULTS: Only less than half of all patients (44.7%) received guideline
      concordant care in the study population. The likelihood of receiving guideline
      concordant care significantly decreased with increasing age, non-white race,
      higher comorbidity score, and lower income. Three-year median survival time
      significantly increased (exceeded 487 days) in patients receiving guideline
      concordant care. Adjusted lung cancer mortality risk significantly increased by
      91% (HR = 1.91, 95% CI: 1.82-2.00) among patients receiving guideline-discordant
      care. CONCLUSION: This study highlights the critical need to address disparities
      in receipt of guideline-concordant lung cancer care among elderly. Although lung
      cancer diagnostic and management services are covered under the Medicare program,
      underutilization of these services is a concern.

PMID- 25604095
TI  - Osteogenic cell sheets reinforced with photofunctionalized micro-thin titanium.
AB  - Cell sheet technology has been used to deliver cells in single-sheet form with an
      intact extracellular matrix for soft tissue repair and regeneration. Here, we
      hypothesized that titanium-reinforced cell sheets could be constructed for bone
      tissue engineering and regeneration. Fifty-um-thick titanium plates containing
      apertures were prepared and roughened by acid etching, some of which were
      photofunctionalized with 12 min of UV light treatment. Cell sheets were prepared
      by culturing rat calvarial periosteum-derived cells on temperature-responsive
      culture dishes and attached to titanium plates. Titanium-reinforced osteogenic
      cell sheet construction was conditional on various technical and material
      factors: cell sheets needed to be double-sided and sandwich the titanium plate,
      and the titanium plates needed to be micro thin and contain apertures to allow
      close apposition of the two cell sheets. Critically, titanium plates needed to be
      UV-photofunctionalized to ensure adherence and retention of cell sheets. Single
      sided cell sheets or double-sided cell sheets on as-made titanium contracted and
      deformed within 4 days of incubation. Titanium-reinforced cell sheets on
      photofunctionalized titanium were structurally stable at least up to 14 days,
      developed the expected osteogenic phenotypes (ALP production and mineralization),
      and maintained structural integrity without functional degradation. Successful
      construction of titanium-reinforced osteogenic cell sheets was associated with
      increased cell attachment, retention, and expression of vinculin, an adhesion
      protein by photofunctionalization. This study identified the technical and
      material requirements for constructing titanium-reinforced osteogenic cell
      sheets. Future in vivo studies are warranted to test these titanium-reinforced
      cell sheets as stably transplantable, mechanically durable, and shape
      controllable osteogenic devices.

PMID- 25604093
TI  - Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk,
      CD4 T cell lymphopenia and survival time.
AB  - Defects in antigen presenting cell function have been implicated in glioma
      immunosuppression. We measured peripheral CCL22, a dendritic cell/macrophage
      derived T cell trafficking chemokine, in sera from 1,208 glioma cases and 976
      controls to assess whether it might provide a biomarker of glioma risk, survival
      and immune dysfunction. Cluster models were used to examine the relationship
      between CCL22 and glioma risk. Patient survival was assessed using Cox regression
      models. We also examined the relationship between CCL22 levels and CD4 cell
      counts, as well as allergy history and IgE levels. CCL22 levels were
      significantly lower among glioma cases compared with controls (Mean +/- SEM: 1.23
      +/- 0.03 ng/mL in cases vs. 1.60 +/- 0.03 ng/mL in controls, p < 0.0001) and this
      difference remained significant even after controlling for other covariates in
      the cluster models (highest quartile versus lowest Odds Ratio = 0.21, p <
      0.0001). CD4 cell counts were positively correlated with CCL22 in glioma cases
      (Spearman r(2) = 0.51, p < 0.01) and were significantly lower in cases compared
      with controls. Higher CCL22 levels were associated with longer survival in all
      cases combined and in GBM cases (hazard ratio(allcases) = 0.81; 95% CI: 0.72
      0.91, p = 0.0003). CCL22 levels were not associated with IgE level or self
      reported allergies. Circulating CCL22 levels are related to both glioma risk and
      survival duration independent of age, histology, grade and IDH mutation status.
      CCL22 should be considered a marker of immune status with potential prognostic
      value.

PMID- 25604096
TI  - Pharmacological management of chronic lower back pain: a review of cost
      effectiveness.
AB  - Lower back pain is one of the most prevalent musculoskeletal conditions in the
      developed world and accounts for significant health services use. The American
      College of Physicians and the American Pain Society have published a joint
      clinical guideline that recommends providing patients with information on
      prognosis and self-management, the use of medications with proven benefits and,
      for those who do not improve, consideration be given to the use of spinal
      manipulation (for acute lower back pain only), interdisciplinary rehabilitation,
      exercise, acupuncture, massage, yoga, cognitive behavioural therapy or
      relaxation. The purpose of this review was to evaluate published economic
      evaluations of pharmacological management for chronic lower back pain. A total of
      seven studies were eligible for inclusion in there view. The quality of the
      economic evaluations undertaken in the included studies was not high. This was
      primarily because of the nature of the underlying clinical evidence, most of
      which did not come from rigorous randomised controlled trials (RCTs), and the
      manner in which it was incorporated into the economic evaluations. All studies
      provided reasonable information about what aspects of healthcare and other
      resource use were identified, measured and valued. However, the reporting of
      total costs was not uniform across studies. Measures of pain and disability were
      the most commonly collected outcomes measures. Two studies collected information
      on quality of life directly from participants while two studies modelled this
      information based on the literature. Future economic evaluations of interventions
      for chronic lower back pain, including pharmacological interventions, should be
      based on the results of well-conducted RCTs where the measurement of costs and
      outcomes such as quality of life and quality-adjusted life-years is included in
      the trial protocol, and which have a follow-up period sufficient to capture
      meaningful changes in both costs and outcomes. In the absence of RCT data,
      economic models should be used to estimate future costs and outcomes using robust
      methods. 

PMID- 25604097
TI  - [National survey on the prevalence and causes of blindness in Peru].
AB  - OBJECTIVE: To estimate the prevalence of blindness and visual impairment among
      adults in Peru and to determine their causes, to evaluate the coverage and
      quality of the cataract surgical services and to investigate the barriers that
      inhibit access to these services. METHODS: A cross-sectional population study
      with two-stage random cluster sampling of individuals of >= 50 years old,
      representative of the entire country, using the standard methodology of the Rapid
      Assessment of Avoidable Blindness. Visual acuity was assessed and the condition
      of the lens and posterior pole examined by direct ophthalmoscopy. Cataract
      surgical coverage was calculated. Its quality, as well as the causes of visual
      acuity < 20/60 and the barriers to accessing surgical treatment were assessed.
      RESULTS: A total of 4 849 people were examined. Blindness prevalence was 2.0%
      (confidence interval of 95%: 1.5-2.5%). The main causes of blindness were
      cataract (58.0%), glaucoma (13.7%) and age-related macular degeneration (11.5%).
      Uncorrected refraction errors were the principal cause of moderate visual
      impairment (67.2%). Cataract surgical coverage was 66.9%. 60.5% of the eyes
      operated for cataracts achieved a visual acuity >= 20/60 with available
      correction. The main barriers to cataract surgery were the high cost (25.9%) and
      people being unaware that treatment was possible (23.8%). CONCLUSIONS: The
      prevalence of blindness and visual impairment in Peru is similar to that of other
      Latin American countries. Given the low cataract surgical coverage and the aging
      of the population, access to the services could be improved by increasing the
      population education on eye health and the response capacity of the
      ophthalmological and cataract surgical services, and by reducing the costs of the
      latter.

PMID- 25604098
TI  - Prevalence of visual impairment in El Salvador: inequalities in educational level
      and occupational status.
AB  - OBJECTIVE: To examine the prevalence of blindness, visual impairment, and related
      eye diseases and conditions among adults in El Salvador, and to explore
      socioeconomic inequalities in their prevalence by education level and
      occupational status, stratified by sex. METHODS: Based upon the Rapid Assessment
      of Avoidable Blindness (RAAB) methodology, this nationwide sample comprised 3 800
      participants (3 399 examined) >= 50 years old from 76 randomly selected clusters
      of 50 persons each. The prevalence of blindness, visual impairment and related
      eye diseases and conditions, including uncorrected refractive error (URE), was
      calculated for categories of education level and occupational status. Multiple
      logistic regression models were fitted to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs) and stratified by sex. RESULTS: Age-adjusted
      prevalence was 2.4% (95% CI: 2.2-2.6) for blindness (men: 2.8% (95% CI: 2.5-3.1);
      women: 2.2% (95% CI: 1.9-2.5)) and 11.8% (95% CI: 11.6-12.0) for moderate visual
      impairment (men: 10.8% (95% CI: 10.5-11.1); women: 12.6% (95% CI: 12.4-12.8)).
      The proportion of visual impairment due to cataract was 43.8% in men and 33.5% in
      women. Inverse gradients of socioeconomic inequalities were observed in the
      prevalence of visual impairment. For example, the age-adjusted OR (AOR) was 3.4
      (95% CI: 2.0-6.4) for visual impairment and 4.3 (95% CI: 2.1-10.4) for related
      URE in illiterate women compared to those with secondary education, and 1.9 (95%
      CI: 1.1-3.1) in cataract in unemployed men. CONCLUSIONS: Blindness and visual
      impairment prevalence is high in the El Salvador adult population. The main
      associated conditions are cataract and URE, two treatable conditions. As
      socioeconomic and gender inequalities in ocular health may herald discrimination
      and important barriers to accessing affordable, good-quality, and timely health
      care services, prioritization of public eye health care and disability policies
      should be put in place, particularly among women, the unemployed, and uneducated
      people.

PMID- 25604099
TI  - [National survey of blindness and avoidable visual impairment in Honduras].
AB  - OBJECTIVES: To determine the prevalence of blindness and visual impairment in
      Honduras, its causes and the response by the health services to growing demand.
      METHODS: A cross-sectional population study was conducted between June and
      December 2013 using the standard methodology of the Rapid Assessment of Avoidable
      Blindness. A random sample survey was done in 63 clusters of 50 individuals aged
      >= 50, representative of the country as a whole. Visual acuity (VA) was assessed
      using a Snellen eye chart, and the condition of the lens and posterior pole was
      examined by direct ophthalmoscopy. Cataract surgical coverage was calculated and
      an assessment made of its quality, the causes of VA < 20/60 and the barriers to
      accessing surgical treatment. RESULTS: A total of 2 999 people were examined
      (95.2% of the forecast total). Blindness prevalence was 1.9% (confidence interval
      of 95%: 1.4-2.4%) and 82.2% of these cases were avoidable. The main causes of
      blindness were unoperated cataracts (59.2%) and glaucoma (21.1%). Uncorrected
      refraction error was the main cause of severe (19.7%) and moderate (58.6%) visual
      impairment. Cataract surgical coverage was 75.2%. 62.5% of the eyes operated for
      cataracts achieved a VA > 20/60 with available correction. The main barriers
      against cataract surgery were cost (27.7%) and the lack of availability or
      difficulty of geographical access to the treatment (24.6%). CONCLUSIONS: The
      prevalence of blindness and visual impairment in Honduras is similar to that of
      other Latin American countries. 67% of cases of blindness could be resolved by
      improving the response capacity of the ophthalmological services, especially of
      cataract surgery, improving optician services and incorporating eye care in
      primary health care.

PMID- 25604100
TI  - Infant and young child feeding in four departments in Haiti: mixed-method study
      on prevalence of recommended practices and related attitudes, beliefs, and other
      determinants.
AB  - OBJECTIVE: To determine and describe the prevalence and patterns of three
      recommended practices for infant and young child feeding-exclusive breastfeeding
      (EB), continued breastfeeding (CB), and achievement of minimum dietary diversity
      in four regions in Haiti, and to identify the attitudes and beliefs that inform
      these practices and any other factors that may facilitate or impede their
      implementation. METHODS: This study utilized a mixed-methods approach consisting
      of 1) a cross-sectional survey (n = 310) and 2) 12 focus group discussions among
      women >=18 years old with children <= 2 years old. Multivariable logistic
      regression analyses were conducted to identify factors associated with 1) EB
      during the first six months of life, 2) CB for children >= 2 years old, and 3)
      receipt of a diverse variety of complementary foods. Qualitative data were
      recorded, transcribed verbatim, and analyzed for common themes. Data were
      collected in June and July 2013 in four departments in Haiti: Artibonite, Nippes,
      Ouest, and Sud-Est. RESULTS: Prevalence of EB, CB, and achievement of minimum
      dietary diversity was 57.0%, 11.9%, and 21.2% respectively. EB was statistically
      significantly associated with infant's age when controlling for annual household
      income, location of most recent birth, or receipt of CB counseling (odds ratio
      (OR) = 0.67 (95% CI: 0.47-0.97)). CB was not statistically significantly
      associated with rural place of residence, receipt of CB counseling, parity, or
      infant's age. Meeting minimum dietary diversity was not significantly associated
      with parity, receipt of postnatal care, rural place of residence, location of
      most recent birth, receipt of infant and young child feeding counseling, or level
      of schooling. Beliefs surrounding the relationship between the mother's health
      and her diet on the quality of breast milk may prohibit EB and CB. Qualitative
      data revealed that dietary diversity may be low because 1) mothers often struggle
      to introduce complementary foods and 2) those that are traditionally introduced
      are not varied and primarily consist of grains and starches. CONCLUSIONS:
      Prevalence of the three recommended infant and young child feeding practices
      examined in this study is suboptimal, particularly CB and achievement of minimum
      dietary diversity. Future communication and programming efforts should address
      the misunderstandings and concerns identified through the qualitative methods
      used in this research.

PMID- 25604101
TI  - A systematic review of the nutritional adequacy of the diet in the Central Andes.
AB  - OBJECTIVE: To examine dietary adequacy in the Andean area, including macro- and
      micronutrient intakes, with a particular focus on rural communities; to highlight
      nutrition priorities in the Andes; and to identify opportunities for improvement.
      METHODS: A comprehensive literature search was conducted, identifying published
      and grey literature in English and Spanish related to diet in the central Andean
      countries of Bolivia, Colombia, Ecuador, and Peru. Articles reporting data from
      dietary surveys or nutrition interventions were included. Thirty-four papers or
      reports published in 1969-2011 were included in the final review. The mean and
      variation in intakes by sex and age group of all presented nutrients were
      collated and the mean of means were calculated. RESULTS: Thiamin, niacin, and
      vitamin C intakes were usually adequate. Intakes of most other micronutrients,
      including iron, zinc, vitamin A, riboflavin, vitamin B12, folate, and zinc were
      low, likely resulting in high levels of inadequacy. Energy intakes were lower
      than requirements, but it is unlikely to be a common problem, rather, this result
      was probably due to the known tendency of most dietary survey tools to
      underreport intake. However, energy from fat intakes was very low, usually less
      than 20% of the total, and in some settings, less than 10%. CONCLUSIONS: The
      inadequate intake of some micronutrients is common in many developing countries,
      but the extremely low intake of dietary fat found in the central Andes is not.
      Increased consumption of animal-source foods would increase fat intakes, while
      addressing micronutrient deficiencies; however, the impact on the fragile
      ecosystem of the Andes needs considering. Indigenous crops, such as lupine bean,
      quinoa, and amaranth are also rich in fat or micronutrients.

PMID- 25604102
TI  - [Physical therapy in pediatric primary care: a review of experiences].
AB  - OBJECTIVE: To review pediatric physical therapy experiences described in the
      literature and to analyze the production of knowledge on physical therapy in the
      context of pediatric primary health care (PPHC). METHODS: A systematic review was
      conducted according to the PRISMA criteria. The following databases were
      searched: MEDLINE, LILACS, SciELO, PubMed, Scopus and Cochrane; Brazilian
      Ministry of Health's CAPES doctoral dissertations database; and System for
      Information on Grey Literature in Europe (SIGLE). The following search terms were
      used: ["primary health care" and ("physical therapy" or "physiotherapy") and
      ("child" or "infant")] and equivalent terms in Portuguese and Spanish, with no
      restriction on publication year. RESULTS: Thirteen articles from six countries
      were analyzed and grouped into three main themes: professional dilemmas (three
      articles), specific competencies and skills required in a PPHC setting (seven
      articles), and practice reports (four articles). Professional dilemmas involved
      expanding the role of physical therapists to encompass community environments and
      sharing the decision-making process with the family, as well as collaborative
      work with other health services to identify the needs of children. The
      competencies and skills mentioned in the literature related to the identification
      of clinical and sociocultural symptoms that go beyond musculoskeletal conditions,
      the establishment of early physical therapy diagnoses, prevention of
      overmedication, and the ability to work as team players. Practice reports
      addressed stimulation in children with neurological diseases, respiratory
      treatment, and establishing groups with mothers of children with these
      conditions. CONCLUSIONS: The small number of studies identified in this review
      suggests that there is little knowledge regarding the roles of physical
      therapists in PPHC and possibly regarding the professional abilities required in
      this setting. Therefore, further studies are required to provide data on the
      field, along with a continuing education effort on the part of physical
      therapists.

PMID- 25604103
TI  - [Chikungunya: a challenge for the Dominican Republic's health services].
AB  - The Region of the Americas has been affected since December 2013 by a chikungunya
      epidemic for the first time. Although the first cases were recorded in the French
      Caribbean, the epidemic quickly spread to the Dominican Republic due to trade and
      people movements. The Dominican Republic, which shares the island of Hispaniola
      with Haiti, has a population of 10 million. This article contains information
      from a range of different publications and official documents about the
      chikungunya virus infection and epidemic. These papers were extremely helpful for
      guiding the response to the epidemic in the Dominican Republic and may also be
      useful for enhancing knowledge of the virus and responses among health workers
      elsewhere in the region. Particular attention is drawn to the important research
      undertaken in countries and territories affected by the epidemic in the Indian
      Ocean area. This is the case, for example, of the island of La Reunion, where the
      epidemic had an attack rate of more than 30% between 2005 and 2007. Researchers
      were able to identify risk groups, severe and atypical forms of the infection,
      cases of vertical transmission, chronic disease causing recurrent pain over three
      years, and directly- or indirectly-related deaths from the virus. Given its high
      attack rate, the chikungunya virus has emerged as an exceptional challenge for
      health ministries and calls for appropriate organized responses from the health
      services, prioritization of care for risk groups and patients exhibiting severe
      forms of the disease, and effective social communication and intersectoral
      actions. 

PMID- 25604104
TI  - [Chikungunya in the Dominican Republic: lessons learned in the first six months].
AB  - The chikungunya epidemic in the Dominican Republic began in February 2014. During
      the first six months 429 421 cases were recorded, representing 65% of all those
      notified to the Pan American Health Organization by 33 countries and territories
      of the Region of the Americas. This epidemic has spread quickly in the Dominican
      Republic, requiring a focused intersectoral response, led by the Ministry of
      Public Health and involving major efforts by the National Epidemiological System
      and the health services network. Given that the virus will affect thousands of
      people, this article seeks to describe the actions that have already been carried
      out, and to share the results and lessons learned during these first months with
      health ministries and professionals in the countries of the Region, in order to
      assist them to prepare an appropriate response to confront the epidemic
      effectively and efficiently. 

PMID- 25604105
TI  - [Virtual Campus of Public Health: six years of human resources education in
      Mexico].
AB  - This paper discusses the gestation process, implementation methodology, and
      results obtained from the initiative to use e-learning to train human resources
      for health, six years after the launch of the Virtual Campus of Public Health of
      the University of Guadalajara (Mexico); the discussion is framed by Pan American
      Health Organization (PAHO) standards and practices. This is a special report on
      the work done by the institutional committee of the Virtual Campus in western
      Mexico to create an Internet portal that follows the guidelines of the strategic
      model established by Nodo Mexico and PAHO for the Region of the Americas. This
      Virtual Campus began its activities in 2007, on the basis of the use of free
      software and institutional collaboration. Since the initial year of
      implementation of the node, over 500 health professionals have been trained using
      virtual courses, the node's educational platform, and a repository of virtual
      learning resources that are interoperable with other repositories in Mexico and
      the Region of the Americas. The University of Guadalajara Virtual Campus
      committee has followed the proposed model as much as possible, thereby achieving
      most of the goals set in the initial work plan, despite a number of
      administrative challenges and the difficulty of motivating committee members. 

PMID- 25604107
TI  - Intramolecular C-H activation through gold(I)-catalyzed reaction of iodoalkynes.
AB  - The cycloisomerization reaction of 1-(iodoethynyl)-2-(1-methoxyalkyl)arenes and
      related 2-alkyl-substituted derivatives gives the corresponding 3-iodo-1
      substituted-1H-indene under the catalytic influence of IPrAuNTf2 [IPr=1,3-bis(2,6
      diisopropyl)phenylimidazol-2-ylidene; NTf2=bis(trifluoromethanesulfonyl)imidate].
      The reaction takes place in 1,2-dichloroethane at 80  degrees C, and the addition
      of ttbp (2,4,6-tri-tert-butylpyrimidine) is beneficial to accomplish this new
      transformation in high yield. The overall reaction implies initial assembly of an
      intermediate gold vinylidene upon alkyne activation by gold(I) and a 1,2-iodine
      shift. Deuterium labeling and crossover experiments, the magnitude of the
      recorded kinetic primary isotopic effect, and the results obtained from the
      reaction of selected stereochemical probes strongly provide support for concerted
      insertion of the benzylic C-H bond into gold vinylidene as the step responsible
      for the formation of the new carbon-carbon bond.

PMID- 25604106
TI  - [Consensus on the diagnostic and therapeutic approach to pain and stress in the
      newborn].
AB  - Pain and stress experienced by the newborn have not been addressed adequately.
      Infants in neonatal intensive care units often undergo painful and stressful
      invasive procedures, and inappropriate treatment increases morbidity and
      mortality. At the 5th Clinical Consensus of the Ibero-American Society of
      Neonatology, 32 neonatologists from the region were invited to establish
      recommendations for the diagnosis and treatment of neonatal pain and stress. Key
      themes were explored based on the best scientific evidence available in indexed
      databases. All attendees participated actively in a meeting in Santiago, Chile,
      with the objective of reaching a consensus on recommendations and conclusions.
      Pain and neonatal stress affect neurological development and long-term behavior
      and require timely diagnosis and appropriate management and treatment, including
      the use of drugs with an appropriate balance between effectiveness and toxicity.
      The Consensus emphasized the importance of assessing pain in the newborn from a
      multidimensional viewpoint, and provided recommendations on the indications and
      limitations for an individualized pharmacological therapy. The use of analgesics
      has precise indications but also important limitations; there is a lack of
      randomized studies in newborns, and adverse effects need to be considered.
      Nonpharmacological measures to mitigate pain were proposed. Stress management
      should begin in the delivery room, including maternal contact, stimulus reduction
      and the implementation of intervention reduction protocols. Recommendations for
      improving clinical practices related to neonatal pain and stress are presented. 

PMID- 25604108
TI  - Direct printing of reduced graphene oxide on planar or highly curved surfaces
      with high resolutions using electrohydrodynamics.
AB  - Electrohydrodynamic inkjet printing of reduced graphene oxide (RGO) is de
      monstrated to form complex geometric devices with high resolution (line width ~ 5
      mm). Both planar and highly curved surfaces (radius of curvature ~ 60 mm) can be
      used as substrates. Demonstrations of counterfeit coin recognition using RGO
      patterns and all-printed RGO transistors suggest substantial promise for
      applications in security and electronics. 

PMID- 25604109
TI  - [Severe pneumonia with hypoxemia is ARDS: yes or not].

PMID- 25604110
TI  - [Look beyond the surface: lactate and oxygen metabolic dysfunction in critical
      patients].

PMID- 25604111
TI  - [The effect of mild sedation on the prognosis and inflammatory markers in
      critical patients with mechanical ventilation].
AB  - OBJECTIVE: To compare the effect of slight and usual sedation on the prognosis
      and inflammatory marker levels in patients receiving mechanical ventilation in
      ICU. METHODS: We enrolled 78 critically ill adult patients who were undergoing
      mechanical ventilation and were expected to need ventilation for more than 48 h.
      The patients were prospectively and randomly assigned to receive: slight sedation
      (Richmond Agitation Sedation Score -1 to 0, n = 38 patients) or usual sedation
      (Richmond Agitation Sedation Score -3 to -2, n = 40 patients). Sedative dosages,
      duration of mechanical ventilation, length of ICU stay, complications (ventilator
      associated pneumonia, tracheotomy) , adverse reactions (accidental extubation,
      reintubation, barotrauma) and levels of inflammatory markers on the day of
      sedation time for 48 h were recorded. RESULTS: When compared with the usual
      sedation group, duration of mechanical ventilation (d) ( 8 +/- 5 vs 13 +/- 8, P <
      0.05) and length of ICU stay (d) ( 12 +/- 10 vs 22 +/- 9, P < 0.05) were
      significantly shorter in the slight sedation group. The total doses of midazolam
      (mg) , propofol (mg) and fentany (ug) were lower in the slight sedation group
      than those in the usual sedation group (275 +/- 85 vs 575 +/- 142, 4 562 +/- 1
      128 vs 7 434 +/- 1 712 and 2 332 +/- 1 458 vs 4 124 +/- 2 743, P < 0.05) .
      Accidental extubation (5% vs 3%) , reintubation (5% vs 10%) and barotraumas (3%
      vs 8%) showed no differences between the 2 groups (P > 0.05). In the slight
      sedation group, the incidences of ventilator-associated pneumonia (26% vs 53%)
      and tracheotomy (18% vs 48%) were significantly decreased compared with those in
      the usual group. The levels of IL-1 (35 +/- 12 vs 47 +/- 18, P < 0.05) ng/L, IL-6
      (49 +/- 21 vs 62 +/- 27, P < 0.05) ng/L, TNF-alpha ( 39 +/- 16 vs 52 +/- 25, P <
      0.05) ng/L and CRP (95 +/- 41 vs 125 +/- 45, P < 0.05) mg/L were also lower in
      the slight sedation group than those in the conventional group. There were no
      differences in ICU mortality and 28 d-survival rate between the 2 groups.
      CONCLUSION: Slight sedation was shown to reduce the length of mechanical
      ventilation and ICU stay. It also decreased the levels of inflammatory markers
      while didn't increase the incidence of adverse reactions.

PMID- 25604112
TI  - [Diagnostic value of serum procalcitonin in identifying the etiology of non
      responding community-acquired pneumonia after initial antibiotic therapy].
AB  - OBJECTIVE: This study was to investigate the diagnostic value of serum
      procalcitonin(PCT) in identifying the etiology of non-responding community
      acquired pneumonia (CAP) after initial antibiotic therapy. METHODS: A
      retrospective analysis was performed for 232 hospitalized CAP patients admitted
      to the People's Hospital of Zhengzhou University during June 2013 and January
      2014. Early treatment failure was defined as the presence of persistent fever
      (>38  degrees C) and/or clinical symptoms (malaise, cough, expectoration,
      dyspnea) or deterioration after at least 72 h of initial antimicrobial treatment,
      or development of respiratory failure requiring mechanical ventilation, or septic
      shock. Bronchoscopy or transthoracic lung biopsy was performed in case of early
      treatment failure when indicated. Serum level of PCT was detected by double
      antibody sandwich method. The differences between 2 or more groups were compared
      using 2-independent student t test, one-way ANOVA; Mann-Whitney U test, Kruskal
      Wallis rank sum test, or chi(2) test. Risk factors and odds ratios for
      nonresponsiveness were analyzed by setting up a Logistic regression model. The
      diagnostic values of PCT were determined by receiver operating characteristic
      curves (ROC curves). RESULTS: Of the 232 CAP patients enrolled, 124 were male and
      108 were female, with an average age of (46 +/- 20) years. Thirty-six patients
      failed to respond to the initial antibiotic therapy. As shown by Logistic
      regression analysis, the risk factors for treatment failure included
      hypoalbuminemia, type 2 diabetes, previous history of splenectomy , PSI 4-5
      grade, and lung infiltration >= 3 lobes. The most common causes of non
      responsiveness were antimicrobial insufficiency (n = 23), and misdiagnosis of
      noninfectious mimics of pneumonia (n = 11), with 2 cases of unidentified
      etiology. The serum PCT level in admission was 0.19 (0.07-0.66) ug/L in the
      antimicrobial insufficiency subgroup, which was significantly higher than that in
      the misdiagnosis subgroup [0.06(0.05-0.08)ug/L; P < 0.01]. The antimicrobial
      insufficiency subgroup included 11 cases of bacterial infection (5 of G(+) cocci
      and 6 of G(-) bacilli) and 12 cases of nonbacterial infection; their PCT levels
      were 0.66(0.19-5.80) ug/L and 0.08(0.05-0.20) ug/L, respectively (P < 0.01).
      There was no statistically significant difference among PCT levels of the 4
      subgroups of nonbacterial infections (4 tuberculosis, 3 fungi, 3 atypical
      pathogens, 2 viruses) (F = 3.025, P = 0.094). The cut-off values of PCT were
      >0.13 ug/L and >0.115 ug/L for differentiating non-responsiveness originated from
      bacterial infection or other causes, and infection vs non-infection, which
      yielded a sensitivity of 100% (11/11) and 65% (14/23) , specificity of 83%
      (19/23) and 91% (10/11) , and AUC of 0.955 and 0.802, respectively. CONCLUSIONS:
      Antibiotic failure to cover the microbial pathogens, infectious complications and
      misdiagnosis are the most common causes of early treatment failure in patients
      with CAP. Serum PCT level fails to predict non-responsiveness, but is suggestive
      of bacterial infections in hospitalized CAP patients with early treatment
      failure.

PMID- 25604113
TI  - [Clinical investigation of detecting the bronchi responsible for pulmonary air
      leakage by injecting methylene blue saline in 27 cases with intractable
      pneumothorax and bronchial fistula].
AB  - OBJECTIVE: To establish a new method for detecting the bronchus responsible for
      pulmonary air leakage by injecting methylene blue saline and to evaluate its
      efficacy and safety in cases with intractable pneumothorax and bronchial fistula.
      METHODS: From January 2006 to October 2013, a total of 19 cases of intractable
      spontaneous pneumothorax and 8 cases of bronchial fistula were recruited in the
      study at the Fourth Hospital affiliated to Hebei Medical University. Of all the
      cases, 15 were diagnosed as having tension pneumothorax and 12 as having
      communicating pneumothorax. All the cases failed to respond to continuous pleural
      suction for more than 5 days and consented to the proposed treatment. Before
      procedure, chest suction was established to allow sustained airflow through the
      drainage tube while the patients breathed normally. Under direct vision through
      fiberoptic bronchoscope, injection catheter was inserted into the bronchoscopy
      channel, and methylene blue saline was slowly injected into the potentially
      leaking segmental or sub-segmental bronchi. When a steady decline or
      disappearance in the amount of methylene blue saline in the airways was observed,
      or methylthionine-tainted saline was detected within the chest drainage tube, the
      bronchus responsible for air leakage was indicated. Before blocking the target
      bronchus, the negative pressure level of pleural suction should be reduced or
      stopped, and then porcine fibrin glue or a-cyanoacrylate was used for sealing the
      bronchi associated with air leakage. When the air was absent from the drainage
      tube, and lung recruitment was indicated in the chest X-ray for 5 days, and
      bronchial blockade of air leakage was proved successful. RESULTS: The bronchi
      responsible for air leakage were successfully located in all 27 cases, among them
      segmental bronchi were located in 16, subsegmental bronchi in 10, and small
      subsegmental bronchus in only one. Multiple adjacent segmental involvement
      occurred in 3, and multiple adjacent subsegmental involvement in 5 cases. The
      average time for locating the target bronchi was (51 +/- 9) s, among them the
      average time for tension pneumothorax was (48 +/- 15) s compared with (53 +/- 16)
      s for communicating pneumothorax (t = 0.416, P = 0.699) . The average amount of
      methylene blue saline consumed for locating the target bronchi was (42 +/- 23)
      ml. During the procedure, the membrane of the bronchi was kept intact, and the
      vital signs were stable. Blockade of the target bronchi was successful with
      fibrin glue in 20 cases and with OB glue in 7 cases. A total of 61 times of
      bronchial blocking were performed, and the airflow of the chest drainage tube was
      instantly stopped in 17 times, gradually stopped in 10, steadily reduced in 22
      and no change in 12 times. Adverse effects included severe cough in 4 cases,
      fever in 3, pleural hemorrhage in 3, and chest pain, atelectasis, and pneumonia
      in 2 cases, respectively. CONCLUSION: The bronchi responsible for pulmonary air
      leakage in patients with spontaneous pneumothorax and bronchial fistula could be
      determined by injecting methylene blue saline into the airways. This novel method
      does not require special instruments, and is easy to perform with a high safety
      and effectiveness.

PMID- 25604114
TI  - [Primary pleural diffuse large B cell lymphoma:a case report and review of
      literature].
AB  - OBJECTIVE: To analyze the clinical features of 1 case of primary pleural diffuse
      large B-cell lymphoma (DLBCL) and therefore to improve the understanding of this
      disease. METHODS: The clinical features, auxiliary examinations and diagnosis of
      a case with DLBCL were reported and the related literatures were reviewed. The
      literature review was carried out respectively with "primary pleural, lymphoma",
      as the search terms in Wanfang Data, CNKI and PubMed by December 2013. RESULTS: A
      73 year-old male patient was admitted to the hospital because of chest pain on
      the left side for 1 month. The main symptoms of the patient were left side chest
      pain, with occasional cough. Chest CT scan showed left pleural effusion and
      pleural thickening. Thoracoscopy was performed and revealed multiple sizes of
      nodules on the visceral and parietal pleura. Pathology study confirmed the
      diagnosis of DLBCL. The patient was treated with CHOP regimen 3 times. So far,
      there was no local recurrence. A total of 12 literatures were retrieved from
      Wanfang Data, CNKI and PubMed, and they were all case reports. There were 8 male
      and 4 female patients, aging from 12 to 81 years. The main symptoms were chest
      pain and fever. CONCLUSIONS: Primary pleural DLBCL is a rare disease. It is
      easily to be misdiagnosed due to non-specific clinical and imaging
      manifestations. The final diagnosis depends ultimately on pathological biopsy,
      and thoracoscopy is the most effective method to confirm DLBCL.

PMID- 25604115
TI  - [A preliminary study of the effect of mitochondrial autophagy on cognitive
      function in rats of early intermittent hypoxia].
AB  - OBJECTIVE: To explore the effect of mitochondrial autophagy on cognitive function
      in rats of early intermittent hypoxia by observing hippocampal CA1 pyramidal cell
      mitochondrial autophagy and the expression of related proteins in a intermittent
      hypoxia(IH) animal model. METHODS: Seventy-two adult male Wistar rats were
      randomly divided into a control group (UC) and a 5% intermittent hypoxia (IH)
      group. The compressed air was given to the UC group while rats in 5% IH group
      suffered from 7-hour IH every day. At 1 d, 3 d, 5 d, 7 d, 10 d and 14 d after the
      completion of the model, transmission electron microscopy was used to observation
      rat hippocampal CA1 pyramidal cell mitochondrial ultrastructural changes, and
      immunohistochemistry assay was used to detect the expression of Beclin-1 and LC3.
      The Morris water test was performed to detect the learning and memory function in
      the rats. RESULTS: Compared with the UC group, the 5% IH group began to show
      mitochondrial size and shape changes, swelling, reduced matrix density, cristae,
      mitochondrial vacuolization, and typical mitochondria autophagosome formation
      from the 3 d. In the 5% IH group, Beclin-1 and LC3 protein expressions were
      significantly increased compared with the UC group (P < 0.05). The expressions of
      Beclin-1 and LC3were different among different time points (P < 0.05); with the
      extension of time, their expressions firstly increased, peaked at 10 d (P <
      0.05), and then decreased at 14 d (P < 0.05). Their expressions in the UC group
      were not different significantly among different time points (P > 0.05). The
      level of learning and memory of the rats in the 5% IH group had no obvious
      changes compared with the UC group at 1 d, 3 d, 5 d, 7 d, and 10 d, but the level
      started to drop at 14 d with a significant difference (P < 0.05) . The level of
      learning and memory of the rats in the UC group was not different among different
      time points (P > 0.05). CONCLUSION: Early intermittent hypoxia induced
      hippocampus mitochondrial autophagy and autophagy-related protein expression in
      rats. Mitochondrial autophagy may reduce the damage to cognitive function of the
      rats exposed to early intermittent hypoxia.

PMID- 25604116
TI  - [The practice of the "ultra" protective lung ventilation strategy: combined
      ventilation mode of extracorporeal membrane oxygenation and high frequency
      oscillatory ventilation].

PMID- 25604117
TI  - [Advances in diaphragmatic function and clinical application].

PMID- 25604118
TI  - [Development of airway humidification].

PMID- 25604119
TI  - [The candidate genes of obstructive sleep apnea hypopnea syndrome].

PMID- 25604120
TI  - Environmental enteropathy and malnutrition: do we know enough to intervene?
AB  - Environmental enteropathy (EE) is a poorly defined state of intestinal
      inflammation without overt diarrhea that occurs in individuals exposed over time
      to poor sanitation and hygiene. It is implicated as a cause of stunting and
      malnutrition, oral vaccine failure and impaired development in children from low
      income countries. The burden on child health of malnutrition alone, which affects
      25% of all children and is estimated to result in more than a million deaths
      annually due to heightened susceptibility to infection, makes urgent a solution
      to EE. Efforts are thus underway to treat EE even while work continues to
      identify it through the use of non-invasive biomarkers, and delineate its
      pathogenesis. A recent study published in BMC Medicine reports the first
      randomized controlled phase I trial of an anti-inflammatory drug for EE. The
      aminosalicylate mesalazine was found to be safe in short-term treatment of a
      small number of severely malnourished children, although efficacy was not
      established. Whether such treatment trials are premature, or instead a way both
      to understand and intervene in EE, is the focus of this article. Please see
      related article: http://www.biomedcentral.com/1741-7015/12/133.

PMID- 25604121
TI  - Sagittal gait patterns in cerebral palsy: the plantarflexor-knee extension couple
      index.
AB  - The identification of gait patterns in cerebral palsy offers a common language
      for clinicians and contributes to management algorithms. We describe a
      quantitative classification of sagittal gait patterns based on the plantarflexor
      knee extension couple index. This consists of a scatter plot based on ankle and
      knee scores, and allows objective identification of the sagittal gait pattern.
      Sagittal kinematic data from 200 limbs of 100 patients with bilateral spastic
      cerebral palsy were utilized to validate the algorithm against the assessment of
      a clinician with expertise in gait pattern identification. A dataset of 776
      cerebral palsy patients, 1552 limbs, was used to compare the sagittal gait
      patterns against k-means statistical clustering. The classification was further
      explored with respect to the knee kinetics during the middle of stance and
      physical examination measurements of the gastrocnemius-soleus complex. Two
      supplementary materials (Appendices 2 and 3) provide in-depth discussion about
      statistical properties of the plantarflexor-knee extension couple index as well
      as its relationship with statistical clustering. The plantarflexor-knee extension
      index achieved 98% accuracy and may be suitable for the computational
      classification of large patient cohorts and multicentre studies. The sagittal
      gait patterns were strongly related to k-means statistical clustering and
      physical examination of the gastrocnemius-soleus complex. Patients in crouch gait
      had normal soleus and gastrocnemius lengths but spasticity in the gastrocnemius.
      Patients in jump gait exhibited a short gastrocnemius and soleus and
      gastrocnemius spasticity. Patients in true equinus presented with a moderately
      contracted soleus and gastrocnemius and gastrocnemius spasticity. Patients in
      apparent equinus did not show abnormal physical examination measurements for the
      gastrocnemius-soleus complex.

PMID- 25604122
TI  - Neurocognitive impairment in a large sample of homeless adults with mental
      illness.
AB  - OBJECTIVE: This study examines neurocognitive functioning in a large, well
      characterized sample of homeless adults with mental illness and assesses
      demographic and clinical factors associated with neurocognitive performance.
      METHOD: A total of 1500 homeless adults with mental illness enrolled in the At
      Home Chez Soi study completed neuropsychological measures assessing speed of
      information processing, memory, and executive functioning. Sociodemographic and
      clinical data were also collected. Linear regression analyses were conducted to
      examine factors associated with neurocognitive performance. RESULTS:
      Approximately half of our sample met criteria for psychosis, major depressive
      disorder, and alcohol or substance use disorder, and nearly half had experienced
      severe traumatic brain injury. Overall, 72% of participants demonstrated
      cognitive impairment, including deficits in processing speed (48%), verbal
      learning (71%) and recall (67%), and executive functioning (38%). The overall
      statistical model explained 19.8% of the variance in the neurocognitive summary
      score, with reduced neurocognitive performance associated with older age, lower
      education, first language other than English or French, Black or Other ethnicity,
      and the presence of psychosis. CONCLUSION: Homeless adults with mental illness
      experience impairment in multiple neuropsychological domains. Much of the
      variance in our sample's cognitive performance remains unexplained, highlighting
      the need for further research in the mechanisms underlying cognitive impairment
      in this population.

PMID- 25604123
TI  - Label-free nanoUPLC-MSE based quantification of antimicrobial peptides from the
      leaf apoplast of Nicotiana attenuata.
AB  - BACKGROUND: Overexpressing novel antimicrobial peptides (AMPs) in plants is a
      promising approach for crop disease resistance engineering. However, the in
      planta stability and subcellular localization of each AMP should be validated for
      the respective plant species, which can be challenging due to the small sizes and
      extreme pI ranges of AMPs which limits the utility of standard proteomic gel
      based methods. Despite recent advances in quantitative shotgun proteomics, its
      potential for AMP analysis has not been utilized and high throughput methods are
      still lacking. RESULTS: We created transgenic Nicotiana attenuata plants that
      independently express 10 different AMPs under a constitutive 35S promoter and
      compared the extracellular accumulation of each AMP using a universal and
      versatile protein quantification method. We coupled a rapid apoplastic peptide
      extraction with label-free protein quantification by nanoUPLC-MSE analysis using
      Hi3 method and identified/quantified 7 of 10 expressed AMPs in the transgenic
      plants ranging from 37 to 91 amino acids in length. The quantitative comparison
      among the transgenic plant lines showed that three particular peptides, belonging
      to the defensin, knottin and lipid-transfer protein families, attained the
      highest concentrations of 91 to 254 pmol per g leaf fresh mass, which identified
      them as best suited for ectopic expression in N. attenuata. The chosen mass
      spectrometric approach proved to be highly sensitive in the detection of
      different AMP types and exhibited the high level of analytical reproducibility
      required for label-free quantitative measurements along with a simple protocol
      required for the sample preparation. CONCLUSIONS: Heterologous expression of AMPs
      in plants can result in highly variable and non-predictable peptide amounts and
      we present a universal quantitative method to confirm peptide stability and
      extracellular deposition. The method allows for the rapid quantification of
      apoplastic peptides without cumbersome and time-consuming purification or
      chromatographic steps and can be easily adapted to other plant species.

PMID- 25604125
TI  - Erratum to: Optimization of Noise in Non-integrated Instrumentation Amplifier for
      the Amplification of Very Low Electrophysiological Signals. Case of Electro
      Cardio Graphic Signals (ECG).

PMID- 25604124
TI  - Modulation of the immune system during postpartum uterine inflammation.
AB  - Postpartum uterine inflammation (endometritis) in the dairy cow is associated
      with lower fertility at both the time of infection and after the inflammation has
      resolved. We hypothesized that aberrant DNA methylation may be involved in the
      subfertility associated with uterine inflammation. The objective of this study
      was to characterize genome-wide DNA methylation and gene expression in the
      endometrium of dairy cows with subclinical endometritis (SCE). Endometrial
      tissues were obtained at 29 days postpartum (n = 12), and microarrays were used
      to characterize transcription and DNA methylation. Analyses revealed 1,856 probes
      differentially expressed in animals with SCE (n = 6) compared with controls (CON,
      n = 6, P < 0.05, Storey Multiple testing correction) and 2,976 probes with
      significant correlation between gene expression and bacteriology score. No
      significant associations among DNA methylation and gene expression were detected.
      Analysis of transcription data using the Database for Annotation, Visualization,
      and Integrated Discovery and Gene Set Enrichment Analysis identified several
      pathways and processes enriched in SCE cows, with the majority related to the
      immune response. Furthermore, the top ontology terms enriched in genes that had
      expression data correlated to bacteriology score were: Defense response,
      inflammatory response, and innate immune response. Gene expression profiles in
      cows with subclinical endometritis in this study indicate that the immune
      response is activated, potentially resulting in a local proinflammatory
      environment in the uterus. If this period of inflammation is prolonged it could
      result in tissue damage or failure to complete involution of the uterus, which
      may create a suboptimal environment for future pregnancy. 

PMID- 25604127
TI  - Coagulation factor XII protease domain crystal structure.
AB  - BACKGROUND: Coagulation factor XII is a serine protease that is important for
      kinin generation and blood coagulation, cleaving the substrates plasma kallikrein
      and FXI. OBJECTIVE: To investigate FXII zymogen activation and substrate
      recognition by determining the crystal structure of the FXII protease domain.
      METHODS AND RESULTS: A series of recombinant FXII protease constructs were
      characterized by measurement of cleavage of chromogenic peptide and plasma
      kallikrein protein substrates. This revealed that the FXII protease construct
      spanning the light chain has unexpectedly weak proteolytic activity compared to
      beta-FXIIa, which has an additional nine amino acid remnant of the heavy chain
      present. Consistent with these data, the crystal structure of the light chain
      protease reveals a zymogen conformation for active site residues Gly193 and
      Ser195, where the oxyanion hole is absent. The Asp194 side chain salt bridge to
      Arg73 constitutes an atypical conformation of the 70-loop. In one crystal form,
      the S1 pocket loops are partially flexible, which is typical of a zymogen. In a
      second crystal form of the deglycosylated light chain, the S1 pocket loops are
      ordered, and a short alpha-helix in the 180-loop of the structure results in an
      enlarged and distorted S1 pocket with a buried conformation of Asp189, which is
      critical for P1 Arg substrate recognition. The FXII structures define patches of
      negative charge surrounding the active site cleft that may be critical for
      interactions with inhibitors and substrates. CONCLUSIONS: These data provide the
      first structural basis for understanding FXII substrate recognition and zymogen
      activation.

PMID- 25604128
TI  - Disease progression pattern in metastatic breast cancer patients treated with
      anti-HER2 therapies.
AB  - PURPOSE: Over the last decade a dramatic improvement in the treatment and
      prognosis of human epidermal growth factor receptor-2 (HER2) positive metastatic
      breast cancer (MBC) has been achieved. This study aimed to describe pattern,
      timing of metastases, and time to progression (TTP) of MBC patients (pts) treated
      with multiple lines of therapy with trastuzumab and/or lapatinib. METHODS:
      Clinical-pathologic features, treatment-lines and metastatic sites were collected
      from the institutional database; TTP was evaluated for each treatment-line. A
      meta-analysis of treatment-line estimates was performed; Q test and I (2)-index
      were used to detect and estimate heterogeneity. Cox's proportional hazards model
      and Fine and Gray's proportional subhazards model in a competing risks setting
      were used to detect differences in hazard rate and to estimate relative risks.
      RESULTS: 112 pts were analyzed. The median number of treatment-lines administered
      was 6 (range 1-17) and 524 (86 %) disease progression events were observed
      (median follow up 4.2 years). Distribution of metastases at baseline remained
      consistent across all lines. Having a given site affected by metastasis was a
      major risk factor of progression in that site. Hormone-receptor-positive pts
      resulted more likely to progress on bone (HR = 1.88). Elderly pts were less
      likely to progress on CNS (HR = 0.73). Median TTP resulted superior to 5 months
      up to the 6th line of treatment, reaching a plateau at the 9th treatment-line.
      CONCLUSIONS: These data suggest that risk factors for progression in HER2
      positive MBC do not significantly differ between various distributions of
      metastases, and that MBC pts benefit from anti-HER2 therapy even in late
      treatment-lines.

PMID- 25604129
TI  - Muscovy duck retinoic acid-induced gene I (MdRIG-I) functions in innate immunity
      against H9N2 avian influenza viruses (AIV) infections.
AB  - Retinoic acid inducible gene I (RIG-I) is a cytosolic pattern recognition
      receptor that senses pathogen-associated molecular patterns (PAMPs). Muscovy duck
      (Cairina moschata) is a large duck different from other species of ducks, and is
      more susceptible to some microbial pathogens. In this study, the Muscovy duck RIG
      I gene (MdRIG-I) was identified. Quantitative RT-PCR showed that MdRIG-I mRNA was
      widely expressed in different tissues, especially in those with mucosa. RIG-I
      null DF-1 cells transfected with DNA constructs encoding MdRIG-I or CARDs domain
      can activate IRF-3 and NF-kappaB to up-regulated activity of IFN-beta promoter.
      The components of the signaling pathway downstream of RIG-I in mammalian cells
      including IRF-3, NF-kappaB, IFN-beta and the IFN-stimulated genes Mx-1, PKR and
      MDA5 were significantly up-regulated in CARDs-overexpressing-DF-1 cells.
      Implicating RIG-I in the antiviral response to an infection in vivo, we found
      that RIG-I expression in brain, spleen, lung and bursa were up-regulated in ducks
      challenged with H9N2 avian influenza virus (AIV), whose six internal genes were
      closely related to the H7N9 and H10N8 AIV. In vitro, DF-1 cells transfected with
      MdRIG-I plasmid can respond significantly to H9N2 AIV, evident through
      enhancement of IFN-beta promoter activity and decreased virus titer. Altogether,
      these results indicated that MdRIG-I is a novel member of RLR gene family,
      engaging in the early stage of antiviral innate immunity. 

PMID- 25604130
TI  - Two dimensional magnetic correlation in the unconventional corrugated layered
      oxides (Ba,Sr)4Mn3O10.
AB  - Both Ba4Mn3O10 and Sr4Mn3O10 crystallize in an orthorhombic crystal structure
      consisting of corrugated layers containing Mn3O12 polydedra. The thermal
      variation of magnetic susceptibility of the compositions consists of a broad hump
      like feature indicating the presence of low dimensional magnetic correlation. We
      have systematically investigated the magnetic data of these compounds and found
      that the experimental results match quite well with the two dimensional
      Heisenberg model of spin-spin interaction. The two dimensional nature of the
      magnetic spin-spin interaction is supported by the low temperature heat capacity
      data of Ba4Mn3O10. Interestingly, both the samples show dielectric anomaly near
      the magnetic ordering temperature indicating multiferroic behavior. 

PMID- 25604131
TI  - Response to Stephen Holgate.

PMID- 25604132
TI  - A comment on "Scientometrics in a changing research landscape".

PMID- 25604133
TI  - The heat shock protein 90 inhibitor, (-)-epigallocatechin gallate, has anticancer
      activity in a novel human prostate cancer progression model.
AB  - (-)-Epigallocatechin gallate (EGCG), a major tea polyphenol, elicits anticancer
      effects. However, the mechanism of action is not fully understood. Our laboratory
      previously showed that EGCG inhibits heat shock protein 90 (HSP90). We used
      nontumorigenic (NT), tumorigenic, and metastatic cancer cells from a novel human
      prostate cancer progression model to test the hypotheses that certain stages are
      more or less sensitive to EGCG and that sensitivity is related to HSP90
      inhibition. Treatment of cells with EGCG, novobiocin, or 17-AAG resulted in more
      potent cytotoxic effects on tumorigenic and metastatic cells than NT cells. When
      tumorigenic or metastatic cells were grown in vivo, mice supplemented with 0.06%
      EGCG in drinking water developed significantly smaller tumors than untreated
      mice. Furthermore, EGCG prevented malignant transformation in vivo using the full
      prostate cancer model. To elucidate the mechanism of EGCG action, we performed
      binding assays with EGCG-Sepharose, a C-terminal HSP90 antibody, and HSP90
      mutants. These experiments revealed that EGCG-Sepharose bound more HSP90 from
      metastatic cells compared with NT cells and binding occurred through the HSP90 C
      terminus. In addition, EGCG bound HSP90 mutants that mimic both complexed and
      uncomplexed HSP90. Consistent with HSP90 inhibitory activity, EGCG, novobiocin,
      and 17-AAG induced changes in HSP90-client proteins in NT cells and larger
      differences in metastatic cells. These data suggest that EGCG may be efficacious
      for the treatment of prostate cancer because it preferentially targets cancer
      cells and inhibits a molecular chaperone supportive of the malignant phenotype.

PMID- 25604134
TI  - A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal
      growth factor receptor signaling in aberrant crypt foci of the colorectum.
AB  - Colorectal cancer progresses through multiple distinct stages that are
      potentially amenable to chemopreventative intervention. Epidermal growth factor
      receptor (EGFR) inhibitors are efficacious in advanced tumors including
      colorectal cancer. There is significant evidence that EGFR also plays important
      roles in colorectal cancer initiation, and that EGFR inhibitors block
      tumorigenesis. We performed a double-blind randomized clinical trial to test
      whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable
      safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal
      aberrant crypt foci (ACF), a subset of which progress to colorectal cancer, and
      normal rectal tissue. A total of 45 patients were randomized to one of three
      erlotinib doses (25, 50, and 100 mg) with randomization stratified by
      nonsteroidal anti-inflammatory drug (NSAID) use. There were no unanticipated
      adverse events with erlotinib therapy. Erlotinib was detected in both normal
      rectal mucosa and ACFs. Colorectal ACF phosphorylated ERK (pERK), phosphorylated
      EGFR (pEGFR), and total EGFR signaling changes from baseline were modest and
      there was no dose response. Overall, this trial did not meet is primary efficacy
      endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely
      insufficient to merit further studies without additional prescreening
      stratification or potentially longer duration of use.

PMID- 25604136
TI  - Treatment of anastomotic leaks with metallic stent after esophagectomies.
AB  - The diagnosis and the treatment of anastomotic leak after esophagectomy are the
      keys to reduce the morbidity and mortality after this surgery. The stent plays an
      important role in the treatment of the leakage and in the prevention of
      reoperation. We have analyzed the database of the section of the esophagogastric
      surgery of Donostia University Hospital from June 2003 to May 2012. It is a
      retrospective study of 113 patients with esophagectomy resulting from tumor, and
      24 (21.13%) of these patients developed anastomotic leak. Of these 24 patients,
      13 (54.16%) have been treated with a metallic stent and 11 (45.84%) without a
      stent. The average age of the patients was 55.69 and 62.45 years, respectively.
      All patients treated with and without a stent have been males. Eight (61.5%)
      stents were placed in the neck and five (38.5%) in the chest. However, among the
      11 fistulas treated without a stent, 9 patients had cervical anastomosis (81.81%)
      and 2 patients (18.18%) had anastomosis in the chest. Twelve patients (92.30%)
      with a stent preserve digestive continuity, and 10 patients (90.90%) were treated
      without a stent. One patient died in the stent group and one in the nonstent
      group. The treatment with metallic stent of the anastomotic leak after
      esophagectomy is an option that can prevent reoperation in these patients, but it
      does not decrease the average of the hospital stay. The stent may be more useful
      in thoracic anastomotic leaks. 

PMID- 25604135
TI  - Coffee drinking and cutaneous melanoma risk in the NIH-AARP diet and health
      study.
AB  - BACKGROUND: Cutaneous melanoma is the fifth most common cancer in the United
      States. Modifiable risk factors, with the exception of exposure to ultraviolet
      radiation (UVR), are poorly understood. Coffee contains numerous bioactive
      compounds and may be associated inversely with melanoma. However, previous
      epidemiological evidence is limited. METHODS: Coffee intake was assessed at
      baseline with a food frequency questionnaire in the National Institutes of Health
      AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer
      free at baseline, 2904 incident cases of malignant melanoma were identified
      during 4 329 044 person-years of follow-up, with a median of 10.5 years of follow
      up. Multivariable-adjusted Cox proportional hazards models were used to estimate
      hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and
      subsequent melanoma risk with non-coffee drinkers as the reference group.
      Statistical tests were two-sided, and P values less than .05 were interpreted as
      statistically significant. RESULTS: The highest category of coffee intake was
      inversely associated with malignant melanoma (>=4 cups/day: HR = 0.80, 95% CI =
      0.68 to 0.93, P trend = .01). This association was statistically significant for
      caffeinated (>=4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P trend = .01) but
      not for decaffeinated coffee (P trend = .55). CONCLUSIONS: Higher coffee intake
      was associated with a modest decrease in risk of melanoma in this large US cohort
      study. Additional investigations of coffee intake and its constituents,
      particularly caffeine, with melanoma are warranted.

PMID- 25604137
TI  - Productivity of Noun Slots in Verb Frames.
AB  - Productivity is a central concept in the study of language and language
      acquisition. As a test case for exploring the notion of productivity, we focus on
      the noun slots of verb frames, such as __want__, __see__, and __get__. We develop
      a novel combination of measures designed to assess both the flexibility and
      creativity of use in these slots. We do so using a rigorously controlled sample
      of child speech and child directed speech from three English-speaking children
      between the ages of 2-3 years and their caregivers. We find different levels of
      creativity and flexibility between the adult and child samples for some measures,
      for some slots, and for some developmental periods. We discuss these differences
      in the context of verb frame semantics, conventionality versus creativity and
      child errors, and draw some tentative conclusions regarding developmental changes
      in children's early grammatical representations. 

PMID- 25604138
TI  - Deprotonation of coordinated phosphanes in a rhenium complex: C-C coupling with
      diimine coligands.
AB  - The reaction of fac-[Re(bipy)(CO)3(PMe3)][OTf] (bipy = 2,2'-bipyridine) with
      KN(SiMe3)2 affords two neutral products: cis,trans-[Re(bipy)(CO)2(CN)(PMe3)], and
      a thermally unstable compound, which features a new C-C bond between a P-bonded
      methylene group (from methyl group deprotonation) and the C6 position of bipy.
      The solid-state structures of more stable 1,2-bis[(2,6
      diisopropylphenyl)imino]acenaphthene analogs, resulting from the deprotonation of
      PMe3, PPhMe2, and PPh2Me ligands, are determined by X-ray diffraction.

PMID- 25604139
TI  - Routine histopathologic examination of "benign" anal lesions: is it necessary?
AB  - PURPOSE: To establish the necessity of routine histopathologic examination of
      specimens from hemorrhoids and anal fistula that are diagnosed preoperatively.
      METHODS: We reviewed histopathologic reports from hemorrhoidectomy and anal
      fistula excision operations performed between 2007 and 2011 in the sixth
      affiliated hospital of Sun Yat-sen University and Guangdong Province Traditional
      Chinese Medical Hospital. We evaluated the incidence of unexpected pathologic
      malignancy and its impact on postoperative management. RESULTS: Among the 10532
      patients recruited, 8308 had undergone hemorrhoidectomy and 2224 had undergone
      excision of an anal fistula. Unexpected pathologic malignancy was discovered in
      17 specimens (0.16 %). Overall and subgroup analysis for risk factors of
      malignant detection revealed unexpected pathologic malignancy was more likely to
      be found in people over the age of 60 years (OR = 5.516, P = 0.002 overall and OR
      = 5.442, P = 0.007 for hemorrhoids). CONCLUSION: Routine histopathologic
      examination of specimens from patients undergoing hemorrhoid or anal fistula
      surgery is of value for identifying unexpected pathologic malignancy. An age
      older than 60 years may be a remarkable risk factor.

PMID- 25604140
TI  - Clinicopathological significance of steroidogenic factor-1 expression in ovarian
      cancer versus ovarian sex cord stromal tumor.
AB  - The significance of steroidogenic factor-1 (SF-1) in human ovarian tumor has not
      been fully investigated. The purposes of this study are to provide a meta
      analysis for SF-1 and to determine whether SF-1 is associated with ovarian tumor
      progression and clinicopathological characteristics. A detailed literature search
      was made for related research publications written in English. Methodological
      quality of the studies was also evaluated. The data were extracted and assessed
      by two reviewers independently. Analysis of pooled data was performed, and odds
      ratio (OR) and corresponding confidence intervals (CIs) were calculated and
      summarized respectively. Final analysis from seven eligible studies was
      performed. Aberrant SF-1 expression was significantly lower in ovarian cancer
      compared to that of normal ovarian tissue (OR = 0.02, 95% CI = 0.00-0.16, p =
      0.0002). However, SF-1 protein expression was not significantly different between
      benign and malignant ovarian tumors (p = 0.35). Interestingly, aberrant SF-1
      expression was significantly higher in ovarian sex cord stromal tumors than that
      of ovarian cancer (OR = 0.00, 95% CI = 0.00-0.01, p < 0.00001). The results of
      this meta-analysis suggest that SF-1 may play an important role in ovarian cancer
      initiation and progression. Moreover, SF-1 expression may serve as a marker in
      the differential diagnosis between ovarian sex cord stromal tumors and ovarian
      cancer.

PMID- 25604141
TI  - MAPK and JAK/STAT pathways targeted by miR-23a and miR-23b in prostate cancer:
      computational and in vitro approaches.
AB  - The long-lasting inadequacy of existing treatments for prostate cancer has led to
      increasing efforts for developing novel therapies for this disease. MicroRNAs
      (miRNAs) are believed to have considerable therapeutic potential due to their
      role in regulating gene expression and cellular pathways. Identifying miRNAs that
      efficiently target genes and pathways is a key step in using these molecules for
      therapeutic purposes. Moreover, computational methods have been devised to help
      identify candidate miRNAs for each gene/pathway. MAPK and JAK/STAT pathways are
      known to have essential roles in cell proliferation and neoplastic transformation
      in different cancers including prostate cancer. Herein, we tried to identify
      miRNAs that target these pathways in the context of prostate cancer as
      therapeutic molecules. Genes involved in these pathways were analyzed with
      various algorithms to identify potentially targeting miRNAs. miR-23a and miR-23b
      were then selected as the best potential candidates that target a higher number
      of genes in these pathways with greater predictive scores. We then analyzed the
      expression of candidate miRNAs in LNCAP and PC3 cell lines as well as prostate
      cancer clinical samples. miR-23a and miR-23b showed a significant downregulation
      in cell line and tissue samples, a finding which is consistent with
      overactivation of these pathways in prostate cancer. In addition, we
      overexpressed miR-23a and miR-23b in LNCAP and PC3 cell lines, and these two
      miRNAs decreased IL-6R expression which has a critical role in these pathways.
      These results suggest the probability of utilizing miR-23a and miR-23b as
      therapeutic targets for the treatment of prostate cancer.

PMID- 25604142
TI  - Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North
      Indians.
AB  - The aim of present study was to evaluate the relationship between vascular
      endothelial growth factor (VEGF) -2578C/A, -2549I/D, -460T/C and -7C/T and VEGFR1
      -710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204
      sporadic breast cancer patients and 204 controls were recruited for this case
      control study. Significantly increased frequency of II genotype of -2549I/D
      polymorphism was observed in patients as compared to control individuals (odds
      ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55-4.92; p = 0.0005). VEGF 
      2578AA genotype (OR = 2.87; 95 % CI, 1.61-5.10; p = 0.0003) and A allele (OR =
      1.65, 95 % CI, 1.25-2.18; p = 0.0004) were found to be associated with increased
      risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI,
      1.25-3.97) and C allele (OR = 1.42, 95 % CI, 1.07-1.87) of VEGF -460T/C
      polymorphism were at higher risk of breast cancer. There was no significant
      difference in genotype and allele distribution of VEGF -7C/T and VEGFR1 -710C/T
      polymorphisms between cases and control individuals (p > 0.05). Linkage
      disequilibrium analysis showed a strong linkage between VEGF -2549I/D and 
      2578C/A polymorphisms (Lewontin's [Formula: see text] = 0.99; r (2) = 0.97), 
      2549I/D and -460T/C ([Formula: see text] = 0.94; r (2) = 0.84), and -2578C/A and 
      460T/C polymorphisms ([Formula: see text] = 0.93; r (2) = 0.83). In the present
      study, we concluded that VEGF -2549I/D, -2578C/A and -460T/C polymorphisms are
      associated with risk to breast cancer in Punjab, North India.

PMID- 25604143
TI  - The role of the UTS2 gene polymorphisms and plasma Urotensin-II levels in breast
      cancer.
AB  - Breast cancer is the most common malignancy predominantly affecting women. To
      date, numerous numbers of studies were reported novel genetic contributors with
      diagnostic, prognostic, and therapeutic potential for the breast carcinogenesis.
      However, the role of urotensin-II in breast carcinogenesis has not been
      elucidated yet. Urotensin-II is a somatostatin-like cyclic tiny peptide
      identified by its potent vasoconstrictor activity. Soon after its discovery, its
      involvement in many disease states as well as its expression in various tissues
      including the tumors have been demonstrated. Moreover, there is strong evidence
      that suggest urotensin-II as the significant contributor of angiogenesis as well
      as cell proliferation and tumor biology. In this study, enzyme-linked
      immunosorbent assay (ELISA) and restriction fragment length polymorphism analysis
      were used to evaluate plasma levels of urotensin-II and Thr21Met and Ser89Asn
      polymorphisms of UTS2 gene in breast cancer patients. In the present case-control
      study, we noticed a significant decrease in the levels of urotensin-II protein in
      the plasma of the breast cancer patients (p < 0.05). Also, Thr21Met polymorphism
      in the UTS2 gene was associated with the risk of developing breast cancer (p <
      0.0001), whereas the genotype frequency of Ser89Asn was found to be similar in
      patients and controls (p > 0.05). In addition, we demonstrated the gradual
      decreasing of urotensin-II protein levels from TT and TM to MM genotypes. In
      conclusion, these results strongly suggest that urotensin-II could contribute to
      breast carcinogenesis and Thr21Met polymorphism can be an important risk factor
      in developing breast tumors.

PMID- 25604145
TI  - Bioinspired near-infrared-excited sensing platform for in vitro antioxidant
      capacity assay based on upconversion nanoparticles and a dopamine-melanin hybrid
      system.
AB  - A novel core-shell structure based on upconversion fluorescent nanoparticles
      (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant
      capacity of biological fluids. In this approach, dopamine-melanin nanoshells
      facilely formed on the surface of UCNPs act as ultraefficient quenchers for
      upconversion fluorescence, contributing to a photoinduced electron-transfer
      mechanism. This spontaneous oxidative polymerization of the dopamine-induced
      quenching effect could be effectively prevented by the presence of various
      antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The
      chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great
      selectivity and sensitivity toward antioxidants relative to other compounds at
      100-fold higher concentration. A satisfactory correlation was established between
      the ratio of the "anti-quenching" fluorescence intensity and the concentration of
      antioxidants. Besides the response of the upconversion fluorescence signal, a
      specific evaluation process for antioxidants could be visualized by the color
      change from colorless to dark gray accompanied by the spontaneous oxidation of
      dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay
      platform was further used to evaluate the antioxidant capacity of cell extracts
      and human plasma, and satisfactory sensitivity, repeatability, and recovery rate
      were obtained. This approach features easy preparation, fluorescence/visual dual
      mode detection, high specificity to antioxidants, and enhanced sensitivity with
      NIR excitation, showing great potential for screening and quantitative evaluation
      of antioxidants in biological systems. 

PMID- 25604146
TI  - Prevalence and determinants of interatrial block in hemodialysis patients.

PMID- 25604144
TI  - Competing endogenous RNA interplay in cancer: mechanism, methodology, and
      perspectives.
AB  - Competing endogenous RNAs (ceRNAs) refer to RNA transcripts, such as mRNAs, non
      coding RNAs, pseudogene transcripts, and circular RNAs, that can regulate each
      other by competing for the same pool of miRNAs. ceRNAs involve in the
      pathogenesis of several common cancers such as prostate cancer, liver cancer,
      breast cancer, lung cancer, gastric cancer, endometrial cancer, and so on. ceRNA
      activity is determined by factors such as miRNA/ceRNA abundance, ceRNAs binding
      affinity to miRNAs, RNA editing, and RNA-binding proteins. The alteration of any
      of these factors may lead to ceRNA network imbalance and thus contribute to
      cancer initiation and progression. There are generally three steps in ceRNA
      research conductions: ceRNA prediction, ceRNA validation, and ceRNA functional
      investigation. Deciphering ceRNA interplay in cancer provides new insight into
      cancer pathogenesis and opportunities for therapy exploration. In this review, we
      try to give readers a concise and reliable illustration on the mechanism,
      functions, research approaches, and perspective of ceRNA in cancer. 

PMID- 25604147
TI  - Evidence for ProTalpha-TLR4/MD-2 binding: molecular dynamics and gravimetric
      assay studies.
AB  - OBJECTIVE: During preconditioning, lipopolysaccharide (LPS) selectively activates
      TLR4/MD-2/Toll/IL-1 receptor-domain-containing adaptor inducing IFN-beta (TRIF)
      pathway instead of pro-inflammatory myeloid differentiation protein-88
      (MyD88)/MyD88-adaptor-like protein (MAL) pathway. Extracellular prothymosin alpha
      (ProTalpha) is also known to selectively activate the TLR4/MD2/TRIF-IRF3 pathway
      in certain diseased conditions. In the current study, biophysical evidence for
      ProTalpha/TLR4/MD-2 complex formation and its interaction dynamics have been
      studied. RESEARCH DESIGN AND METHODS: Gravimetric assay was used to investigate
      ProTalpha/TLR4/MD-2 complex formation while molecular dynamics (MD) simulation
      was used to study its interaction dynamics. RESULTS: Through electrostatic
      interaction, full-length ProTalpha (F-ProTalpha) C-terminal peptide (aa 91 - 111)
      superficially interacts with similar TLR4/MD-2 (KD = 273.36 nm vs 16.07 MUg/ml
      [LPS]) conformation with LPS at an overlapping three-dimensional space while F
      ProTalpha is hinged to the TLR4 scaffold by one-amino acid shift-Mosoian domain
      (aa-51 - 90). Comparatively, F-ProTalpha better stabilizes MD-2 metastable states
      transition and mediates higher TLR4/MD-2 interaction than LPS. CONCLUSIONS:
      ProTalpha via its C-terminal peptide (aa 91 - 111) exhibits in vitro biophysical
      contact with TLR4/MD-2 complex conformation recognized by LPS at overlapping LPS
      binding positions.

PMID- 25604148
TI  - Readmission due to driveline infection can be predicted by new score by using
      serum albumin and body mass index during long-term left ventricular assist device
      support.
AB  - Survival in patients with continuous flow left ventricular assist device (CF
      LVAD) had been increased owing to improved perioperative management procedures.
      The second target for successful long-term LVAD treatment was to reduce
      readmission especially due to device-specific infection, which was one of the
      major unsolved complications. Among 57 enrolled patients who had received CF LVAD
      and been followed for 530 days on median at our institute between 2008 and 2014,
      21 patients experienced readmission due to driveline infection (DLI) at 190 days
      after the surgery on median. Considering the result of Uni/Multivariate Cox
      regression analyses demonstrating lower serum albumin concentration (S-ALB)
      (hazard ratio 0.144) and body mass index (BMI) (hazard ratio 0.843) both obtained
      at discharge were independent predictors of readmission due to DLI, we
      constructed a New Score "7 * [S-ALB (g/dL)] + [BMI]", which significantly
      stratified readmission-free rate into 3 groups [low (>50 Pt), intermediate (44-50
      Pt), and high risk group (<44 Pt)] during 2-year study period (p = 0.008).
      Survival remained unchanged irrespective of DLI, whereas those with DLI needed
      longer in-hospital treatment (p < 0.05). In conclusion, readmission due to DLI
      could be predicted by using two simple nutrition parameters at discharge. Early
      nutrition assessment and intervention may reduce readmission and improve
      patients' quality of life during long-term LVAD support.

PMID- 25604149
TI  - Sutureless aortic valve replacement using a novel autologous tissue heart valve
      with stent (stent biovalve): proof of concept.
AB  - We developed an autologous, trileaflet tissue valve ("biovalve") using in-body
      tissue architecture technology to overcome the disadvantages of current
      bioprosthetic valves. We designed a novel biovalve with a balloon-expandable
      stent: the stent biovalve (SBV). This study evaluated the technical feasibility
      of sutureless aortic valve replacement using the SBV in an orthotopic position,
      as well as the functionality of the SBV under systemic circulation, in an acute
      experimental goat model. Three adult goats (54.5-56.1 kg) underwent sutureless
      AVR under cardiopulmonary bypass (CPB). The technical feasibility and
      functionality of the SBVs were assessed using angiography, pressure
      catheterization, and two-dimensional echocardiography. The sutureless AVR was
      successful in all goats, and all animals could be weaned off CPB. The mean aortic
      cross-clamp time was 45 min. Angiogram, after weaning the animals off CPB, showed
      less than mild paravalvular leakage and central leakage was not detected in any
      of the goats. The mean peak-to-peak pressure gradient was 6.3 +/- 5.0 mmHg.
      Epicardial two-dimensional echocardiograms showed smooth leaflet movement,
      including adequate closed positions with good coaptation; the open position
      demonstrated a large orifice area (average aortic valve area 2.4 +/- 0.1 cm2).
      Sutureless AVR, using SBVs, was feasible in a goat model. The early valvular
      functionalities of the SBV were sufficient; future long-term experiments are
      needed to evaluate its durability and histological regeneration potential.

PMID- 25604152
TI  - [Summary of EBCOG council minutes, Brussels, November 2014].

PMID- 25604150
TI  - The impact of livestock on the abundance, resting behaviour and sporozoite rate
      of malaria vectors in southern Tanzania.
AB  - BACKGROUND: Increases in the coverage of long-lasting insecticidal nets (LLINs)
      have significantly reduced the abundance of Anopheles gambiae sensu stricto in
      several African settings, leaving its more zoophagic sibling species Anopheles
      arabiensis as the primary vector. This study investigated the impact of livestock
      ownership at the household level on the ecology and malaria infection rate of
      vectors in an area of Tanzania where An. arabiensis accounts for most malaria
      transmission. METHODS: Mosquito vectors were collected resting inside houses,
      animal sheds and in outdoor resting boxes at households with and without
      livestock over three years in ten villages of the Kilombero Valley, Tanzania.
      Additionally, the abundance and sporozoite rate of vectors attempting to bite
      indoors at these households was assessed as an index of malaria exposure.
      RESULTS: The mean abundance of An. gambiae s.l. biting indoors was similar at
      houses with and without livestock. In all years but one, the relative proportion
      of An. arabiensis within the An. gambiae s.l. species complex was higher at
      households with livestock. Livestock presence had a significant impact on malaria
      vector feeding and resting behaviour. Anopheles arabiensis were generally found
      resting in cattle sheds where livestock were present, and inside houses when
      absent. Correspondingly, the human blood index of An. arabiensis and An. funestus
      s.l. was significant reduced at households with livestock, whereas that of An.
      gambiae s.s. was unaffected. Whilst there was some evidence that sporozoite rates
      within the indoor-biting An. gambiae s.l population was significantly reduced at
      households with livestock, the significance of this effect varied depending on
      how background spatial variation was accounted for. CONCLUSIONS: These results
      confirm that the presence of cattle at the household level can significantly
      alter the local species composition, feeding and resting behaviour of malaria
      vectors. However, the net impact of this livestock-associated variation in
      mosquito ecology on malaria exposure risk was unclear. Further investigation is
      required to distinguish whether the apparently lower sporozoite rates observed in
      An. gambiae s.l. at households with livestock is really a direct effect of cattle
      presence, or an indirect consequence of reduced risk within areas where livestock
      keepers choose to live.

PMID- 25604151
TI  - [Obesity and primiparity: Risky delivery?].
AB  - OBJECTIVES: To evaluate the risk of materno-foetal complications in obese
      primiparous women (Body Mass Index (BMI)>=30) MATERIALS AND METHODS: A
      retrospective study was conducted in our tertiary referral labour ward from 1st
      January 2009 to 31st December 2010, including primiparous women delivering living
      cephalic singleton pregnancies after 37 weeks of amenorrhea. Two groups were
      compared: obese patients (BMI>=30) and non-obese (BMI<30). Obstetrical and
      neonatal data were collected. RESULTS: Among 1636 primiparous women, 132 (8%) had
      a BMI>=30. Induction of labor, prolonged pregnancy and post-partum hemorrhage
      were significatively more frequent in obese group (P<0.001). Those patients have
      an increased risk of cesarean section (P<0.001). Mean birth weight of newborns
      from obese mothers is significatively higher (3493g vs 3265g, P<0.001), as is the
      frequency of macrosomia (16.7% vs 5.2%, P<0.001). CONCLUSION: Obesity is
      associated with obstetrical complications in primiparous obese women, who are to
      be considered risky patients at their arrival in the labour ward, and specific
      obstetrical management must be planned to improve maternal and neonatal outcomes.

PMID- 25604155
TI  - Multiple coronary artery-pulmonary artery-bronchial artery fistulas.

PMID- 25604154
TI  - Effect of hyperbaric oxygen treatment on irradiated oral mucosa: microvessel
      density.
AB  - The aim of this study was to evaluate the effect of hyperbaric oxygen therapy
      (HBOT) on microvascular tissue and cell proliferation in the oral mucosa. Twenty
      patients, aged 51-78 years, were allocated randomly to a treatment or a control
      group. All had a history of radiotherapy (50-70 Gy) to the orofacial region 2-6
      years previously. Tissue samples were taken from the irradiated buccal oral
      mucosa before HBOT and at 6 months after treatment. In the control group, tissue
      samples were taken on two occasions, 6 months apart. The samples were subjected
      to immunohistochemistry staining: double staining with CD31 and D2-40 for
      microvessels, or Ki-67 for the analysis of cell proliferation. Blood vessel
      density and area were significantly increased after HBOT (P=0.002-0.041). D2-40
      positive lymphatic vessels were significantly increased in number and area in the
      sub-epithelial area (P=0.002 and P=0.019, respectively). No significant
      differences were observed in the control group. There were no significant
      differences in Ki-67-expressing epithelial cells between the two groups. It is
      concluded that the density and area of blood and lymphatic vessels in the
      irradiated mucosa are increased by HBOT 6 months after therapy. Epithelial cell
      proliferation is not affected by HBOT.

PMID- 25604156
TI  - Re: "Predictors of poor clinical outcome following hip fracture in middle-aged
      patients".

PMID- 25604153
TI  - [Does prenatal diagnosis modify neonatal management and early outcome of children
      with esophageal atresia type III?].
AB  - OBJECTIVE: Evaluate neonatal management and outcome of neonates with either a
      prenatal or a post-natal diagnosis of EA type III. STUDY DESIGN: Population-based
      study using data from the French National Register for EA from 2008 to 2010. We
      compared children with prenatal versus post-natal diagnosis in regards to
      prenatal, maternal and neonatal characteristics. We define a composite variable
      of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and
      mortality at 1 year. RESULTS: Four hundred and eight live births with EA type III
      were recorded with a prenatal diagnosis rate of 18.1%. Transfer after birth was
      lower in prenatal subset (32.4% versus 81.5%, P<0.001). Delay between birth and
      first intervention was not significantly different. Defect size (2cm vs 1.4cm,
      P<0.001), gastrostomy (21.6% versus 8.7%, P<0.001) and length in neonatal unit
      care were higher in prenatal subset (47.9 days versus 33.6 days, P<0.001). The
      composite variables were higher in prenatal diagnosis subset (38.7% vs 26.1%,
      P=0.044). CONCLUSION: Despite the excellent survival rate of EA, cases with
      antenatal detection have a higher morbidity related to the EA type (longer gap).
      Even if it does not modify neonatal management and 1-year outcome, prenatal
      diagnosis allows antenatal parental counseling and avoids post-natal transfer.

PMID- 25604157
TI  - High-resolution melting (HRM) re-analysis of a polyposis patients cohort reveals
      previously undetected heterozygous and mosaic APC gene mutations.
AB  - Familial adenomatous polyposis is most frequently caused by pathogenic variants
      in either the APC gene or the MUTYH gene. The detection rate of pathogenic
      variants depends on the severity of the phenotype and sensitivity of the
      screening method, including sensitivity for mosaic variants. For 171 patients
      with multiple colorectal polyps without previously detectable pathogenic variant,
      APC was reanalyzed in leukocyte DNA by one uniform technique: high-resolution
      melting (HRM) analysis. Serial dilution of heterozygous DNA resulted in a lowest
      detectable allelic fraction of 6% for the majority of variants. HRM analysis and
      subsequent sequencing detected pathogenic fully heterozygous APC variants in 10
      (6%) of the patients and pathogenic mosaic variants in 2 (1%). All these variants
      were previously missed by various conventional scanning methods. In parallel, HRM
      APC scanning was applied to DNA isolated from polyp tissue of two additional
      patients with apparently sporadic polyposis and without detectable pathogenic APC
      variant in leukocyte DNA. In both patients a pathogenic mosaic APC variant was
      present in multiple polyps. The detection of pathogenic APC variants in 7% of the
      patients, including mosaics, illustrates the usefulness of a complete APC gene
      reanalysis of previously tested patients, by a supplementary scanning method. HRM
      is a sensitive and fast pre-screening method for reliable detection of
      heterozygous and mosaic variants, which can be applied to leukocyte and polyp
      derived DNA.

PMID- 25604158
TI  - Pregnancy related listeriosis: treatment and control.
AB  - Listeriosis during pregnancy usually presents as an unremarkable febrile illness
      in the mother but can be fatal for the fetus and newborn. Reliable laboratory
      testing for early diagnosis is lacking. Serological antibody tests and
      bacteriological stool tests are not helpful since Listeria-specific antibodies
      and stool cultures yielding the organism can be found in healthy pregnant women.
      Because early diagnosis is difficult, diagnosis is usually made by culturing the
      pathogen from blood, cerebrospinal fluid, placenta or meconium. The mortality
      rate for fetal and newborn listeriosis remains approximately 20%. Two to three
      cases of pregnancy-associated listeriosis are reported annually in Austria among
      approximately 79,000 births, 20-30 cases are reported annually in Germany among
      approximately 680,000 births and 50-100 cases are reported annually in the USA
      among approximately 4 million births. Although Listeria infections in pregnancy
      are rare, they should be considered as a cause of fever of unknown origin during
      pregnancy. 

PMID- 25604159
TI  - Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1
      in normal and diseased bladder detrusor muscles: a clinico-pathological study.
AB  - BACKGROUND: To investigate the expression of parathyroid hormone (PTH)/PTH
      related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and
      diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant
      that functions via PTH1R. We hypothesized that suppression of this axis could be
      involved in the pathogenesis of bladder disease. METHODS: PTH1R expression in
      clinical samples was examined by immunohistochemistry. Normal kidney tissue from
      a patient with renal cancer and bladder specimens from patients undergoing
      ureteral reimplantation for vesicoureteral reflux or partial cystectomy for
      urachal cyst were examined as normal control organs. These were compared with 13
      diseased bladder specimens from patients undergoing bladder augmentation. The
      augmentation patients ranged from 8 to 31 years old (median 15 years), including
      9 males and 4 females. Seven patients had spinal disorders, 3 had posterior
      urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome).
      RESULTS: Renal tubules, detrusor muscle and blood vessels in normal control
      bladders stained positive for PTH1R. According to preoperative urodynamic studies
      of augmentation patients, the median percent bladder capacity compared with the
      age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal
      capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93
      ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five
      cases (38.5%). All augmented bladders showed negative stainings in PTH1R
      expression in the detrusor tissue, but positive staining of blood vessels in
      majority of the cases. CONCLUSIONS: Downregulation of PTH1R may be involved in
      the pathogenesis of human end-stage bladder disease requiring augmentation.

PMID- 25604161
TI  - Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity
      of evocarpine.
AB  - AIMS: The interaction of quinolone and indoloquinazoline alkaloids concerning
      their antimycobacterial activity was studied. METHODS AND RESULTS: The
      antimycobacterial and modulating activity of evodiamine (1), rutaecarpine (2) and
      evocarpine (3) was tested on mycobacteria including three multidrug-resistant
      (MDR) clinical isolates of Mycobacterium tuberculosis. Antagonistic effects were
      concluded from fractional inhibitory concentration (FICI) values. Interaction
      energies of the compounds were calculated using GLUE docking module implemented
      in GRID. 1 and 2 exhibited weak inhibition of rapidly growing mycobacteria,
      however, 1 was active against Myco. tuberculosis H37Rv (MIC = 10 mg l(-1) ) while
      2 was inactive. Both 1 and 2 showed a marked antagonistic effect on the
      susceptibility of different mycobacterial strains to 3 giving FICI values between
      5 and 9. The interaction energies between compounds 1 and 2 with compound 3
      suggested the possibility of complex formation in solution. CONCLUSIONS:
      Indoloquinazoline alkaloids markedly reduce the antimycobacterial effect of the
      quinolone alkaloid evocarpine. Complex formation may play a role in the
      attenuation of its antimycobacterial activity. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study gives a striking example of antagonism between compounds
      present in the same plant extract which should be considered in natural product
      based screening projects.

PMID- 25604162
TI  - Dosage assessment of valnemulin in pigs based on population pharmacokinetic and
      Monte Carlo simulation.
AB  - To estimate the valnemulin pharmacokinetic profile in a swine population and to
      assess a dosage regimen for increasing the likelihood of optimization. This study
      was, respectively, performed in 22 sows culled by p.o. administration and in 80
      growing-finishing pigs by i.v. administration at a single dose of 10 mg/kg to
      develop a population pharmacokinetic model and Monte Carlo simulation. The
      relationships among the plasma concentration, dose, and time of valnemulin in
      pigs were illustrated as C(i,v) = X(0 )(8.4191 * 10(-4) * e(-0.2371t) + 1.2788 *
      10(-5) * e(-0.0069t)) after i.v. and C(p.o) = X(0) (-8.4964 * 10(-4) * e(
      0.5840t) + 8.4195 * e(-0.2371t) + 7.6869 * 10(-6) * e(-0.0069t)) after p.o. Monte
      Carlo simulation showed that T(>MIC) was more than 24 h when a single daily
      dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031
      mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to
      valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase
      the risk of treatment failure and/or drug resistance.

PMID- 25604163
TI  - Modelling of Microalgae Culture Systems with Applications to Control and
      Optimization.
AB  - Mathematical modeling is becoming ever more important to assess the potential,
      guide the design, and enable the efficient operation and control of industrial
      scale microalgae culture systems (MCS). The development of overall, inherently
      multiphysics, models involves coupling separate submodels of (i) the intrinsic
      biological properties, including growth, decay, and biosynthesis as well as the
      effect of light and temperature on these processes, and (ii) the physical
      properties, such as the hydrodynamics, light attenuation, and temperature in the
      culture medium. When considering high-density microalgae culture, in particular,
      the coupling between biology and physics becomes critical. This chapter reviews
      existing models, with a particular focus on the Droop model, which is a precursor
      model, and it highlights the structure common to many microalgae growth models.
      It summarizes the main developments and difficulties towards multiphysics models
      of MCS as well as applications of these models for monitoring, control, and
      optimization purposes.

PMID- 25604165
TI  - Method to measure the force to pull and to break pin bones of fish.
AB  - A texture measurement device was modified to measure the force required to pull
      pin bones from King salmon (Oncorhynchus tshawytscha), snapper (Pagrus auratus),
      and kahawai (Arripis trutta). Pulled bones were also subjected to tension to
      measure the breaking force. For all fish, the pulling force depended on the size
      of the fish, and on the length of the pin bone (P < 0.05). In general, larger
      fish required greater pulling force to remove pin bones. For example, fresh small
      salmon (about 1500 g whole) required 600 g on average to pull pin bones, and
      large fish (about 3700 g whole) required 850 g. Longer bones required greater
      pulling force. The breaking force followed the same trend. In general, the
      breaking force was greater than the pulling force. This allows the removal of the
      bones without breaking them. There was no statistically significant (P > 0.05)
      difference between the forces (both pulling and breaking) from fresh and
      frozen/thawed samples, although in general frozen/thawed samples required less
      force to pull. With the quantification of pulling and breaking forces for pin
      bones, it is possible to design and build better, "more intelligent" pin bone
      removal equipment. 

PMID- 25604164
TI  - Modeling the Growth of Filamentous Fungi at the Particle Scale in Solid-State
      Fermentation Systems.
AB  - Solid-state fermentation (SSF) with filamentous fungi is a promising technique
      for the production of a range of biotechnological products and has the potential
      to play an important role in future biorefineries. The performance of such
      processes is intimately linked with the mycelial mode of growth of these fungi:
      Not only is the production of extracellular enzymes related to morphological
      characteristics, but also the mycelium can affect bed properties and,
      consequently, the efficiency of heat and mass transfer within the bed. A
      mathematical model that describes the development of the fungal mycelium in SSF
      systems at the particle scale would be a useful tool for investigating these
      phenomena, but, as yet, a sufficiently complete model has not been proposed. This
      review presents the biological and mass transfer phenomena that should be
      included in such a model and then evaluates how these phenomena have been modeled
      previously in the SSF and related literature. We conclude that a discrete lattice
      based model that uses differential equations to describe the mass balances of the
      components within the system would be most appropriate and that mathematical
      expressions for describing the individual phenomena are available in the
      literature. It remains for these phenomena to be integrated into a complete model
      describing the development of fungal mycelia in SSF systems.

PMID- 25604160
TI  - Risk of non-AIDS-defining events among HIV-infected patients not yet on
      antiretroviral therapy.
AB  - OBJECTIVES: Certain non-AIDS-related diseases have been associated with
      immunodeficiency and HIV RNA levels in HIV-infected patients on combination
      antiretroviral therapy (cART). We aimed to investigate these associations in
      patients not yet on cART, when potential antiretroviral-drug-related effects are
      absent and variation in RNA levels is greater. METHODS: Associations between, on
      the one hand, time-updated CD4 counts and plasma HIV RNA and, on the other hand,
      a composite non-AIDS-related endpoint, including major cardiovascular diseases,
      liver fibrosis/cirrhosis, and non-AIDS-related malignancies, were studied with
      multivariate Poisson regression models in 12 800 patients diagnosed with HIV
      infection from 1998 onwards while not yet treated with cART. RESULTS: During 18
      646 person-years of follow-up, 203 non-AIDS-related events occurred. Compared
      with a CD4 count >= 500 cells/MUL, adjusted relative risks (RRs) for the
      composite endpoint were 4.71 [95% confidence interval (CI) 2.98-7.45] for a CD4
      count < 200 cells/MUL, 2.06 (95% CI 1.38-3.06) for a CD4 count of 200-349
      cells/MUL, and 1.19 (95% CI 0.82-1.74) for a CD4 count of 350-499 cells/MUL.
      There was no evidence for an independent association with HIV RNA. Other
      important covariates were age [RR 1.40 (95% CI 1.31-1.49) per 5 years older],
      hepatitis B virus coinfection [RR 5.66 (95% CI 3.87-8.28)] and hepatitis C virus
      coinfection [RR 9.26 (95% CI 6.04-14.2)]. CONCLUSIONS: In persons not yet
      receiving cART, a more severe degree of immunodeficiency rather than higher HIV
      RNA levels appears to be associated with an increased risk of our composite non
      AIDS-related endpoint. Larger studies are needed to address these associations
      for individual non-AIDS-related events.

PMID- 25604167
TI  - [In Process Citation].

PMID- 25604166
TI  - Reply: To PMID 25385504.

PMID- 25604168
TI  - [In Process Citation].

PMID- 25604169
TI  - [In Process Citation].

PMID- 25604170
TI  - Malignant mesothelioma trends in Chihuahua, Mexico.

PMID- 25604171
TI  - Risk factors associated to diabetes in Mexican population and phenotype of the
      individuals who will convert to diabetes.
AB  - OBJECTIVE: To describe risk factors associated to the incidence of type 2
      diabetes (T2D) in Mexican population and to define phenotypic (clinical,
      anthropometric, metabolic) characteristics present in the individual who will
      convert to diabetes, regardless of time of onset. MATERIALS AND METHODS: The
      Mexico City Diabetes Study began in 1990, with 2 282 participants, and had three
      subsequent phases: 1994, 1998, and 2008. A systematic evaluation with an oral
      glucose tolerance test was performed in each phase. For diagnosis of T2D,
      American Diabetes Association criteria were used. RESULTS: The population at risk
      was 1939 individuals. Subjects who were in the converter stage (initially non
      diabetic that eventually converted to T2D) had, at baseline, higher BMI (30 vs
      27), systolic blood pressure (119 vs 116 mmHg), fasting glucose (90 vs 82mg/dl),
      triglycerides (239 vs 196mg/dl), and cholesterol (192 vs 190mg/dl), compared with
      subjects who remained non converters (p<0.05). CONCLUSION: The phenotype
      described represents a potentially identifiable phase and a target for preventive
      intervention.

PMID- 25604172
TI  - [HIV seroprevalence among Mexicans age 15 to 49: results from the National Health
      & Nutrition Survey 2012].
AB  - OBJECTIVE: To estimate the HIV seroprevalence among Mexicans aged 15 to 49 years
      old and living in households, and to describe the profile of serorreactive
      individuals. MATERIALS AND METHODS: Cross-sectional study with a national
      probabilistic sample of individuals aged 15 to 49 years with behavioral data from
      direct interview (face-to-face) at households and HIV screening using capillary
      blood collected from the same individuals. RESULTS: A seroprevalence of 0.15%
      (95%CI 0.09-0.21) was estimated for Mexicans aged 15 to 49; seroprevalence among
      women was 0.07% (95%CI 0.03-0.11) and 0.24% (95%CI 0.11-0.36) for men. HIV
      serorreactive population is composed of younger men, with a higher socioeconomic
      level compared to the general population, and with a higher insurance coverage
      social protection on health in general and social security in particular. Only
      50% of the serorreactive individuals may be aware of their status as living with
      HIV. CONCLUSIONS: The estimated HIV seroprevalence in the NHNS 2012 suggests a
      stable pattern since 2000. The estimated prevalence among individuals 15 to 49
      years was adjusted both for selection bias correction and to include MSM
      estimations (under the assumption that MSM is a population hard to reach in a
      household survey), resulting in a total seroprevalence of 0.23% and an estimated
      number of people with HIV of 140,000.

PMID- 25604173
TI  - [Intentional search and reclassification of maternal deaths in Mexico: The effect
      on the distribution of causes].
AB  - OBJECTIVE: To correct the misclassification and improve the quality of
      information on maternal mortality in Mexico. MATERIALS AND METHODS: Using
      clinical records and verbal autopsies, we studied all deaths certified as
      maternal deaths as well as a selection of deaths of women of childbearing age
      whose causes were considered as suspected of hiding a maternal death, all of
      which occurred during 2011 within Mexico. RESULTS: The deliberate search of
      maternal deaths and reclassification allowed the rescue of just over 100 deaths
      that were not originally registered or coded as maternal and confirmed or
      corrected the causes of death recorded on death certificates as confirmed
      maternal deaths. This procedure also allowed the reclassification of 297 maternal
      deaths of women in the groundwork of the National Institute of Statistics and
      Geography. CONCLUSIONS: International Search and Reclassification of Maternal
      Deaths is a very useful procedure for improving the classification of cases that
      were not classified as maternal deaths and the effect was greater with the coding
      of indirect obstetric deaths.

PMID- 25604174
TI  - Scale and scope economies in Mexican private medical units.
AB  - OBJECTIVE: To evaluate technical efficiency and potential presence of scale and
      scope economies in Mexican private medical units (PMU) that will improve
      management decisions. MATERIALS AND METHODS: We used data envelopment analysis
      methods with inputs and outputs for 2 105 Mexican PMU published in 2010 by the
      Instituto Nacional de Estadistica y Geografia from the "Estadistica de Unidades
      Medicas Privadas con Servicio de Hospitalizacion (PEC-6-20-A)" questionnaire.
      RESULTS: The application of the models used in the paper found that there is a
      marginal presence of economies of scale and scope in Mexican PMU. CONCLUSIONS:
      PMU in Mexico must focus to deliver their services on a diversified structure to
      achieve technical efficiency.

PMID- 25604175
TI  - [Risk analysis of brucelosis in the state of Tlaxcala].
AB  - OBJECTIVE: To identify the risk of brucellosis in the state of Tlaxcala, Mexico.
      MATERIALS AND METHODS: A diagnosis of social type was conducted in the
      municipalities of Huamantla, Ixtenco and Teacalco, located in the eastern region
      of the state. The seroprevalence of brucellosis in goats and humans was
      determined. RESULTS: 46.9% of producers know the programs of vaccination against
      brucellosis; 19.7% apply the vaccine and 80.3% do not apply the vaccine.
      Huamantla had the highest seroprevalence of animal brucellosis in 66.8%; San Jose
      Teacalco distributes unpasteurized cheeses to a distance of 270 km, increasing
      the risk of infection with brucellosis. Ixtenco recorded the highest prevalence
      of brucellosis in humans, with 1.51%. CONCLUSION: The municipalities studied
      present risks of infection and spread of brucellosis.

PMID- 25604176
TI  - Effect of particulate matter less than 10um (PM10) on mortality in Bogota,
      Colombia: a time-series analysis, 1998-2006.
AB  - OBJECTIVE: To analyze the association between daily mortality from different
      causes and acute exposure to particulate matter less than 10 microns in
      aerodynamic diameter (PM10), in Bogota, Colombia. MATERIALS AND METHODS: A time
      series ecological study was conducted from 1998 to 2006. The association between
      mortality (due to different causes) and exposure was analyzed using single and
      distributed lag models and adjusting for potential confounders. RESULTS: For all
      ages, the cumulative effect of acute mortality from all causes and respiratory
      causes increased 0.71% (95%CI 0.46-0.96) and 1.43% (95%CI 0.85-2.00),
      respectively, per 10ug/m3 increment in daily average PM10 with a lag of three
      days before death. Cumulative effect of mortality from cardiovascular causes was 
      0.03% (95%CI -0.49-0.44%) with the same lag. CONCLUSIONS: The results suggest an
      association between an increase in PM10 concentrations and acute mortality from
      all causes and respiratory causes.

PMID- 25604177
TI  - Effect of socioeconomic status on the association between air pollution and
      mortality in Bogota, Colombia.
AB  - OBJECTIVE: To evaluate the modification effect of socioeconomic status (SES) on
      the association between acute exposure to particulate matter less than 10 microns
      in aerodynamic diameter (PM10) and mortality in Bogota, Colombia. MATERIALS AND
      METHODS: A time-series ecological study was conducted (1998-2006). The localities
      of the cities were stratified using principal components analysis, creating three
      levels of aggregation that allowed for the evaluation of the impact of SES on the
      relationship between mortality and air pollution. RESULTS: For all ages, the
      change in the mortality risk for all causes was 0.76% (95%CI 0.27-1.26) for SES I
      (low), 0.58% (95%CI 0.16-1.00) for SES II (mid) and -0.29% (95%CI -1.16-0.57) for
      SES III (high) per 10ug/m3 increment in the daily average of PM10 on day of
      death. CONCLUSIONS: The results suggest that SES significantly modifies the
      effect of environmental exposure to PM10 on mortality from all causes and
      respiratory causes.

PMID- 25604178
TI  - Some current challenges in research on air pollution and health.
AB  - This commentary addresses some of the diverse questions of current interest with
      regard to the health effects of air pollution, including exposure-response
      relationships, toxicity of inhaled particles and risks to health, multipollutant
      mixtures, traffic-related pollution, accountability research, and issues with
      susceptibility and vulnerability. It considers the challenges posed to
      researchers as they attempt to provide useful evidence for policy-makers relevant
      to these issues. This commentary accompanies papers giving the results from the
      ESCALA project, a multi-city study in Latin America that has an overall goal of
      providing policy-relevant results. While progress has been made in improving air
      quality, driven by epidemiological evidence that air pollution is adversely
      affecting public health, the research questions have become more subtle and
      challenging as levels of air pollution dropped. More research is still needed,
      but also novel methods and approaches to address these new questions. 

PMID- 25604179
TI  - [Professional education and work of indigenous health agents in the Brazilian
      health system].
AB  - OBJECTIVE: To discuss the role of indigenous health agents in the implementation
      of the model of differentiated attention or intercultural health in Brazil.
      MATERIALS AND METHODS: We revised the scientific literature about the work and
      professional education of indigenous health agents in the Brazilian indigenous
      health system. RESULTS: There is a subordination of the agents to the hegemonic
      medical model. With regards to professional education, we observe the absence and
      irregularity of these processes, with a general emphasis the biomedicine. There
      are conflicts with the health team and community, with devaluation of the agents.
      The agent does not plays the role of mediator between the different health
      knowledge and practices. CONCLUSIONS: We suggest that the discussion of the model
      of differentiated attention should strengthen the relationship between the health
      system and the selfcare.

PMID- 25604180
TI  - [A first analysis of research on social determinants of health in Mexico: 2005
      2012].
AB  - OBJECTIVE: To examine the research on social determinants of health (SDH)
      produced in Mexico during the period 2005-2012, based on the characterization of
      the national health research system and the scientific production on this topic.
      MATERIALS AND METHODS: Two-stage analyses: Review of Mexican documents and
      official sources on health research and systematic bibliographic review of the
      literature on SDH. RESULTS: Although SDH were mentioned in the Specific Action
      Plan for Health Research 2007-2012, they are not implemented in strategies and
      goals, as the emphasis is put mostly in infrastructure and administrative aspects
      of research. In the period studied, 145 articles were published on SDH topics
      such as health conditions, health systems and nutrition and obesity. CONCLUSIONS:
      In spite of the availability of research on SDH in Mexico, the operationalization
      of such findings into health policies has not been possible. The current
      Sectorial Program on Health 2013-2018 represents a window of opportunity to
      position research findings that promote health equity policies.

PMID- 25604181
TI  - [Chikungunya fever in Mexico: confirmed case and notes on the epidemiologic
      response].
AB  - Chikungunya fever (CHIK) is a viral disease transmitted to human beings by the
      same vector as dengue -the Aedes mosquito. Besides fever and severe pain in the
      joints, it produces other symptoms such as myalgias, headache, nausea, fatigue
      and exanthema. There is no specific treatment for it; the therapeutic management
      of patients focuses on symptom relief. Historically, outbreaks of large
      proportions have been reported; even since 2010 it was considered to be a
      potential emerging epidemic. In 2013 it was introduced into the islands of the
      Caribbean, and it has recently been reported in the American continent. This
      paper describes the first confirmed case of chikungunya in Mexico -in the
      municipality of Tlajomulco de Zuniga, Jalisco, in May, 2014-, which was imported
      from the Caribbean island of Antigua and Barbuda by a 39 year-old woman. 

PMID- 25604182
TI  - [Dr. Ciro de Quadros (1940-2014)].

PMID- 25604184
TI  - Diagnostic contribution of cardiac magnetic resonance in patients with acute
      coronary syndrome and culprit-free angiograms.
AB  - BACKGROUND: In spite of robust knowledge about underlying ischemic myocardial
      damage, acute coronary syndromes (ACS) with culprit-free angiograms raise
      diagnostic concerns. The present study aimed to evaluate the additional value of
      cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests,
      for the differentiation of myocardial injury in patients with ACS and non
      obstructed coronary arteries. MATERIAL/METHODS: Patients with ACS, elevated hs
      TnT, and a culprit-free angiogram were prospectively enrolled into the study
      between January 2009 and July 2013. After initial evaluation with standard tests
      (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial
      infarction (AMI) in coronary angiogram, patients were referred for CMR with the
      suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the
      result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non
      injured myocardium as assessed by late gadolinium enhancement. RESULTS: Out of
      5110 patients admitted with ACS, 75 had normal coronary angiograms and entered
      the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC.
      After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC
      (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional
      diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of
      unrecognized AMI. CONCLUSIONS: The study results suggest that the evaluation of
      patients with ACS and culprit-free angiogram should be complemented by a CMR
      examination, if available, because the initial work-up with non-CMR tests leads
      to a significant proportion of misdiagnosed AMI.

PMID- 25604186
TI  - Engineered adenoviruses combine enhanced oncolysis with improved virus production
      by mesenchymal stromal carrier cells.
AB  - Oncolytic viruses have demonstrated in pre-clinical and clinical studies safety
      and a unique pleiotropic activity profile of tumor destruction. Yet, their
      delivery suffers from virus inactivation by blood components and sequestration to
      healthy tissues. Therefore, mesenchymal stromal cells (MSCs) have been applied as
      carrier cells for shielded virus delivery to tumors after ex vivo infection with
      oncolytic viruses. However, infection and particle production by MSCs have
      remained unsatisfying. Here, we report engineered oncolytic adenoviruses (OAds)
      for improved virus production and delivery by MSCs. OAds are uniquely amenable to
      molecular engineering, which has facilitated improved tumor cell destruction. But
      for MSC-mediated regimens, OAd engineering needs to achieve efficient infection
      and replication in both MSCs and tumor cells. We show that an Ad5/3 chimeric OAd
      capsid, containing the adenovirus serotype 3 cell-binding domain, strongly
      increases the entry into human bone marrow-derived MSCs and into established and
      primary pancreatic cancer cells. Further, we reveal that OAd with engineered post
      entry functions-by deletion of the anti-apoptotic viral gene E1B19K or expression
      of the death ligand TRAIL--markedly increased virus titers released from MSCs,
      while MSC migration was not hampered. Finally, these virus modifications, or
      viral expression of FCU1 for local 5-FC prodrug activation, improved tumor cell
      killing implementing complementary cytotoxicity profiles in a panel of pancreatic
      cancer cell cultures. Together, our study establishes post-entry modification of
      OAd replication for improving virus delivery by carrier cells and suggests a
      panel of optimized OAds for future clinical development in personalized treatment
      of pancreatic cancer.

PMID- 25604185
TI  - Pyrosequencing analysis of a bacterial community associated with lava-formed soil
      from the Gotjawal forest in Jeju, Korea.
AB  - In this study, we analyzed the bacterial diversity in soils collected from Gyorae
      Gotjawal forest, where globally unique topography, geology, and ecological
      features support a forest grown on basalt flows from 110,000 to 120,000 years ago
      and 40,000 to 50,000 years ago. The soils at the site are fertile, with rocky
      areas, and are home to endangered species of plants and animals. Rainwater
      penetrates to the groundwater aquifer, which is composed of 34% organic matter
      containing rare types of soil and no soil profile. We determined the bacterial
      community composition using 116,475 reads from a 454-pyrosequencing analysis.
      This dataset included 12,621 operational taxonomic units at 3% dissimilarity,
      distributed among the following groups: Proteobacteria (56.2%) with 45.7% of
      alpha-Proteobacteria, Actinobacteria (25%), Acidobacteria (10.9%), Chloroflexi
      (2.4%), and Bacteroidetes (0.9%). In addition, 16S rRNA gene sequences were
      amplified using polymerase chain reaction and domain-specific primers to
      construct a clone library based on 142 bacterial clones. These clones were
      affiliated with the following groups: Proteobacteria (56%) with 51% of alpha
      Proteobacteria, Acidobacteria (7.8%), Actinobacteria (17.6%), Chloroflexi (2.1%),
      Bacilli (1.4%), Cyanobacteria (2.8%), and Planctomycetes (1.4%). Within the
      phylum Proteobacteria, 56 of 80 clones were tentatively identified as 12
      unclassified genera. Several new genera and a new family were discovered within
      the Actinobacteria clones. Results from 454-pyrosequencing revealed that 57% and
      34% of the sequences belonged to undescribed genera and families, respectively.
      The characteristics of Gotjawal soil, which are determined by lava morphology,
      vegetation, and groundwater penetration, might be reflected in the bacterial
      community composition.

PMID- 25604187
TI  - Successful emergency ablation of ventricular tachycardia in the early
      postoperative period after left ventricular assist device implantation.

PMID- 25604188
TI  - The several roles of stimuli in token reinforcement.
AB  - Three experiments were conducted with pigeons to identify the stimulus functions
      of tokens in second-order token-reinforcement schedules. All experiments employed
      two-component multiple schedules with a token-reinforcement schedule in one
      component and a schedule with equivalent response requirements and/or reinforcer
      density in the other. In Experiment 1, response rates were lower under a token
      reinforcement schedule than under a tandem schedule with the same response
      requirements, suggesting a discriminative role for the tokens. In Experiment 2,
      response rates varied systematically with signaling functions of the tokens in a
      series of conditions designed to explore other aspects of the temporal
      correlative relations between tokens and food. In Experiment 3, response rates
      were reduced but not eliminated by presenting tokens independent of responding,
      yoked to their temporal occurrence in a preceding token component, suggesting
      both a reinforcing function and eliciting/evocative functions based on stimulus
      food relations. Only when tokens were removed entirely was responding eliminated.
      On the whole, the results suggest that tokens, as stimuli temporally correlated
      with food, may serve multiple stimulus functions in token-reinforcement
      procedures--reinforcing, discriminative, or eliciting--depending on the precise
      arrangement of the contingencies in which they are embedded.

PMID- 25604190
TI  - Proteome analysis of porcine epidemic diarrhea virus (PEDV)-infected Vero cells.
AB  - Porcine epidemic diarrhea virus (PEDV) causes an acute, highly contagious, and
      devastating viral enteric disease with a high mortality rate in suckling pigs. A
      large-scale outbreak of PED occurred in China in 2010, with PEDV emerging in the
      United States in 2013 and spreading rapidly, posing significant economic and
      public health concerns. In this study, LC-MS/MS coupled to iTRAQ labeling was
      used to quantitatively identify differentially expressed cellular proteins in
      PEDV-infected Vero cells. We identified 49 differentially expressed cellular
      proteins, of which 8 were upregulated and 41 downregulated. These differentially
      expressed proteins were involved in apoptosis, signal transduction, and stress
      responses. Based on these differentially expressed proteins, we propose that PEDV
      might utilize apoptosis and extracellular signal regulated kinases pathways for
      maximum viral replication. Our study is the first attempt to analyze the protein
      profile of PEDV-infected cells by quantitative proteomics, and we believe our
      findings provide valuable information with respect to better understanding the
      host response to PEDV infection. 

PMID- 25604189
TI  - Candidate gene-environment interactions in breast cancer.
AB  - Gene-environment interactions have the potential to shed light on biological
      processes leading to disease, identify individuals for whom risk factors are most
      relevant, and improve the accuracy of epidemiological risk models. We review the
      progress that has been made in investigating gene-environment interactions in the
      field of breast cancer. Although several large-scale analyses have been carried
      out, only a few significant interactions have been reported. One of these, an
      interaction between CASP8-rs1045485 and alcohol consumption has been replicated,
      but others have not, including LSP1- rs3817198 and parity, and 1p11.2-rs11249433
      and ever being parous. False positive interactions may arise if the gene and
      environment are correlated and the causal variant is less frequent than the tag
      SNP. We conclude that while much progress has been made in this area it is still
      too soon to tell whether gene-environment interactions will fulfil their promise.
      Before we can make this assessment we will need to replicate (or refute) the
      reported interactions, identify the causal variants that underlie tag-SNP
      associations and validate the next generation of epidemiological risk models. 

PMID- 25604191
TI  - Transition-metal-free intramolecular carbene aromatic substitution/Buchner
      reaction: synthesis of fluorenes and [6,5,7]benzo-fused rings.
AB  - Intramolecular aromatic substitution and Buchner reaction have been established
      as powerful methods for the construction of polycyclic compounds. These reactions
      are traditionally catalyzed by Rh(II) catalysts with alpha-diazocarbonyl
      compounds as the substrates. Herein a transition-metal-free intramolecular
      aromatic substitution/Buchner reaction is presented. These reactions use readily
      available N-tosylhydrazones as the diazo compound precursors and show wide
      substrate scope. 

PMID- 25604192
TI  - Endocytosis. A new gateway into cells.
AB  - Two studies have determined the molecular mechanisms that underlie a specific
      clathrin-independent pathway for the internalization of activated surface
      receptors and bacterial toxins.

PMID- 25604196
TI  - RNA metabolism. Promoters drive alternative polyadenylation.
AB  - The RNA-binding protein Elav is recruited in the fruit fly to promoter regions,
      possibly by paused RNA polymerase II, to promote alternative polyadenylation.

PMID- 25604197
TI  - Stem cells. Human primordial germ cells in a dish.
AB  - A robust method to induce primordial germ cells from human pluripotent stem cells
      has been developed, highlighting the importance of SOX17 in the specification of
      the human germline.

PMID- 25604198
TI  - Protein folding. Phosphorylation regulates IDP folding.
AB  - A new study shows that phosphorylation regulates the folding, and thus biological
      function, of the intrinsically disordered protein 4E-BP2.

PMID- 25604195
TI  - Spatiotemporal regulation of the anaphase-promoting complex in mitosis.
AB  - The appropriate timing of events that lead to chromosome segregation during
      mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these
      processes can contribute to tumorigenesis. Key mitotic regulators are controlled
      through ubiquitylation and proteasome-mediated degradation. The APC/C (anaphase
      promoting complex; also known as the cyclosome) is an E3 ubiquitin ligase that
      has a crucial function in the regulation of the mitotic cell cycle, particularly
      at the onset of anaphase and during mitotic exit. Co-activator proteins,
      inhibitor proteins, protein kinases and phosphatases interact with the APC/C to
      temporally and spatially control its activity and thus ensure accurate timing of
      mitotic events. 

PMID- 25604199
TI  - Chromatin. Drivers of nuclear organization.
AB  - Chromatin decondensation is sufficient to induce the relocation of loci from the
      periphery to the centre of nuclei.

PMID- 25604200
TI  - Organelle dynamics: Organelles under the spotlight.

PMID- 25604202
TI  - Renin-angiotensin system blockade in the treatment of heart failure and the role
      of valsartan in this treatment.
AB  - Heart failure which occurs due to various causes including primarily coronary
      artery diseases and hypertension is a syndrome with complex physiopathology and
      clinic that can impair patients' quality of life or lead to death. However, it is
      well known that the activation of renin-angiotensin system (RAS) has an important
      role in the physiopathology of heart failure with reduced ejection fraction.
      Therefore, suppression of this system for achieving a gain in the treatment of
      the disease has been among prominent concerns. In this review, the place of RAS
      suppressive drugs and valsartan, which is an angiotensin receptor blocker, in
      heart failure will be examined. 

PMID- 25604203
TI  - Renal and metabolic effects of valsartan.
AB  - It is known that the drugs which suppress the renin-angiotensin-aldosterone
      system can prevent target organ damage, independent of their blood pressure
      lowering effects. Besides, it has been reported that this group of drugs has
      positive metabolic effects. There are many studies showing that valsartan, being
      an angiotensin receptor blocker and widely used in hypertension treatment, has
      cardioprotective and renoprotective effects in high risk patients. It has been
      seen in these studies that, valsartan treatment has a decreasing effect on
      proteinuria, independent of its blood pressure lowering effects in the patients
      having either diabetic and non-diabetic nephropathy. In this review, the studies
      investigating the renal effects of valsartan will be mentioned. Additionally, the
      studies about the metabolic effects of valsartan will be reported. 

PMID- 25604204
TI  - Hypertension and valsartan.
AB  - Hypertension, which is pointed to be the most frequent cause of death in the
      World and in Turkey and defined by the World Health Organization as global health
      crisis and the prominent risk factor for cardiovascular diseases, is a problem
      threatening public health. Renin-angiotensin system (RAS) plays an important role
      in pathophysiology and in turn treatment of the disease. The drugs suppressing
      RAS are recommended both for monotherapy and combinations. Together with the
      blood pressure lowering effects and positive contributions of this group of drugs
      to the cardiovascular and renal process have been proved by clinical studies. In
      this review, the recent developments about the hypertension treatment were
      summarized and the place of valsartan molecule, being an angiotensin receptor
      blocker in hypertension treatment, was examined in the light of the studies in
      which the effectiveness, tolerability and safety of valsartan were evaluated. 

PMID- 25604205
TI  - Valsartan after myocardial infarction.
AB  - One of the important problems of the patients undergoing acute myocardial
      infarction (MI) is early development of heart failure. It has been revealed in
      various studies that renin-angiotensin-aldosterone system (RAAS) has a
      significant role in this process. The studies conducted with angiotensin
      converting enzyme (ACE) inhibitors have resulted in decreased mortality rate.
      Another RAAS blocker which was discovered about ten years later than other ACE
      inhibitors in historical process is angiotensin receptor blockers (ARB)
      inhibiting the efficiency of angiotensin 2 by binding to angiotensin 1 receptor.
      Valsartan is one of the molecules of this group, which has higher number of large
      scale randomized clinical studies. In this review, following presentation of a
      general overview on heart failure after acute MI, the efficiency of ARBs in this
      patient group will be discussed. This discussion will mostly emphasize the
      construction, outcomes and clinical importance of VALIANT (VALsartan In Acute
      myocardial iNfarcTion), which is the study on valsartan after acute MI heart
      failure. 

PMID- 25604207
TI  - Abecedarium: Who Am I? Y'....

PMID- 25604206
TI  - Randomized controlled trial of a minimal versus extended Internet-based
      intervention for problem drinkers: study protocol.
AB  - BACKGROUND: Problem drinking causes great harm to the person and to society. Most
      problem drinkers will never seek treatment. The current trial will test the
      efficacy of two Internet interventions for problem drinking - one minimal and the
      other extended - as an alternate means of providing help to those in need.
      METHODS/DESIGN: A double blinded, four-wave panel design with random assignment
      to two experimental conditions will be used in this study. Participants will be
      recruited through a comprehensive recruitment strategy consisting of online and
      print advertisements asking for people who are 'interested in helping us develop
      and evaluate Internet-based interventions for problem drinkers.' Potential
      participants will be screened to select problem drinkers who have home access to
      the Internet. Participants will be sent to a password-protected Internet site
      and, upon signing in, will be randomized to be provided access to the minimal or
      extended Internet-based intervention. Six-month, twelve-month, and two-year
      drinking outcomes will be compared between experimental conditions. The primary
      hypothesis is that participants in the extended Internet intervention condition
      will display significantly improved drinking outcomes at twelve months compared
      to participants in the minimal intervention. DISCUSSION: The findings of this
      trial will contribute to the growing literature on Internet interventions for
      problem drinkers. In addition, findings from this trial will contribute to the
      scarce literature available evaluating the long-term efficacy of brief
      interventions for alcohol problems. TRIAL REGISTRATION: Clinical Trials.gov #
      NCT01874509; First submitted June 17, 2013.

PMID- 25604208
TI  - In vitro performance of QLF system and conventional methods for detection of
      occlusal caries around tooth-colored restorations in primary molars.
AB  - BACKGROUND: Secondary caries is the main reason for restoration replacement, and
      therefore, an accurate detection of this type of condition is fundamental. AIM:
      To compare in vitro the performance of different conventional and quantitative
      light-induced fluorescence-based (QLF) methods in detecting occlusal caries
      around resin composite restorations in primary molars. DESIGN: Two examiners
      evaluated independently 42 sites adjacent to tooth-colored restorations using
      visual inspection (ICDAS-CARS), radiographic examination, and QLF. Histological
      examination was used as reference standard method. Area under the ROC curve (Az),
      sensitivity, specificity, and accuracy of the methods were calculated at enamel
      (D1) and dentin caries (D3) lesions thresholds. Intra- and interexaminer
      reproducibility were calculated using intraclass correlation coefficient (ICC)
      and kappa statistics. RESULTS: There was no difference among the methods
      considering Az at D1 threshold. Visual inspection, radiograph, and QLF (scores)
      methods presented similar sensitivities and significantly higher than those
      obtained with the QLF (?F%). At D3 threshold, there were no differences among the
      methods regarding sensitivities, specificities, and accuracy, except for the
      examiner 2 with the QLF (?F%) who achieved a very low sensitivity value.
      CONCLUSION: Conventional methods are similar to QLF methods for detecting caries
      around tooth-colored restorations in primary teeth.

PMID- 25604209
TI  - Pleasure, affection, and love among Black men who have sex with men (MSM) versus
      MSM of other races: countering dehumanizing stereotypes via cross-race
      comparisons of reported sexual experience at last sexual event.
AB  - Black men have historically been stereotyped as hedonistic, aggressive, and
      animalistic in their sexual interactions. This study sought to describe pleasure,
      affection, and love experienced by Black men who have sex with men (MSM) during
      their last male-partnered sexual event and to examine differences relative to
      White, Latino, and Asian MSM. A total of 21,696 (793 Black, 18,905 White, 1,451
      Latino, and 547 Asian) U.S. men ages 18-87 (M Age = 39) were recruited from
      social/sexual networking sites targeting MSM in 2010-2011. Participants reported
      multiple dimensions of sexual experience (pleasure, affection, and love)
      occurring at their last male-partnered sexual event, partner relationship, and
      sociodemographic characteristics. Across relationship categories, a sizeable
      percentage of Black MSM reported pleasure (72-87  % orgasmed, 57-82 % experienced
      high subjective pleasure) and affection (70-91 % kissed, 47-90 % cuddled). Love
      was primarily reported for events involving main partners (felt love for partner:
      96 %; felt loved by partner: 97 %; verbalized love to partner: 89 %). Latent
      class analysis with MSM of all races, adjusting for partner relationship and
      sociodemographic characteristics, revealed three distinct profiles of sexual
      experience: affection and love (Class 1); affection in the absence of love (Class
      2); and neither affection nor love (Class 3). Pleasure was probable across
      profiles. Some racial differences in profile probability were present, but no
      overall pattern emerged. Contrary to Black male stereotypes, Black MSM commonly
      reported pleasure, affection, and love at their last male-partnered sexual event
      and did not show a meaningful pattern of difference from other-race MSM in their
      likelihood of experiencing all three. 

PMID- 25604211
TI  - Unprecedented iminobenzosemiquinone and iminobenzoquinone coordinated mononuclear
      Cu(ii) complex formation under air.
AB  - Two non-innocent 2-anilino-4,6-di-tert-butylphenol units were connected through
      an -ortho bridging S atom and provided the ligand . The ligand reacted with
      CuCl2.2H2O in the presence of Et3N under air and generated a mononuclear Cu(ii)
      complex (1, [CuL(S(IBQ/ISQ))Cl](0)). A single crystal X-ray diffraction analysis
      confirmed that in the complex one of the two 2-anilido-4,6-di-tert-butylphenol
      arms was present in its one-electron oxidized iminobenzosemiquinone form, while
      the other was in its two-electron oxidized iminobenzoquinone form. The
      monoradical-containing Cu(ii) complex was diamagnetic in nature owing to a strong
      antiferromagnetic coupling between the single electron containing dx(2)-y(2)
      magnetic orbital of Cu(ii) and the radical-centered unpaired electron. 

PMID- 25604210
TI  - Comparative computational analysis of pluripotency in human and mouse stem cells.
AB  - Pluripotent cells can be subdivided into two distinct states, the naive and the
      primed state, the latter being further advanced on the path of differentiation.
      There are substantial differences in the regulation of pluripotency between human
      and mouse, and in humans only stem cells that resemble the primed state in mouse
      are readily available. Reprogramming of human stem cells into a more naive-like
      state is an important research focus. Here, we developed a pipeline to reanalyze
      transcriptomics data sets that describe both states, naive and primed
      pluripotency, in human and mouse. The pipeline consists of identifying regulated
      start-ups/shut-downs in terms of molecular interactions, followed by functional
      annotation of the genes involved and aggregation of results across conditions,
      yielding sets of mechanisms that are consistently regulated in transitions
      towards similar states of pluripotency. Our results suggest that one published
      protocol for naive human cells gave rise to human cells that indeed share
      putative mechanisms with the prototypical naive mouse pluripotent cells, such as
      DNA damage response and histone acetylation. However, cellular response and
      differentiation-related mechanisms are similar between the naive human state and
      the primed mouse state, so the naive human state did not fully reflect the naive
      mouse state. 

PMID- 25604212
TI  - Evolving editorial processes at the Journal of Occupational Rehabilitation.

PMID- 25604213
TI  - Ion selective optodes: from the bulk to the nanoscale.
AB  - This review describes recent advances in the miniaturization of ion selective
      optodes into microscale and nanoscale sensors. The topics include a comparison
      between film-based and miniaturized ion optodes, equilibrium and exhaustive
      detection modes, recent preparation methodologies and applications of microscale
      and nanoscale ion optodes, criteria for the design of optode sensors, and other
      future perspectives. 

PMID- 25604214
TI  - Paradigms and public policies on drought in northeast Brazil: a historical
      perspective.
AB  - This paper describes the evolution of drought-related public policies in
      Northeast Brazil (NEB). Using a historical approach, we show that the evolution
      of public policy has not been characterized by abrupt shifts, but has instead
      been shaped through debates between renowned intellectuals. The resulting public
      policies formed a hydrological infrastructure that delivers clean water needed
      for robust economic activity. However, outcomes of the 2012-2013 drought show
      that populations that depend on rain fed agriculture are as vulnerable to drought
      as they were at the start of the 20th century. Although government, social, and
      emergency programs have aided drought victims, drought analysts agree that rain
      fed agriculture has remained vulnerable since drought policies were first
      formulated. Drought policies formulate integrated water resources management
      (IWRM) strategies that are geared toward supplying safe drinking water, and
      debates surrounding the IWRM paradigm have been affected by outcomes of major
      international events such as the World Water Forum. 

PMID- 25604215
TI  - Deforestation and forest fires in Roraima and their relationship with
      phytoclimatic regions in the northern Brazilian Amazon.
AB  - Deforestation and forest fires in the Brazilian Amazon are a regional-scale
      anthropogenic process related to biomass burning, which has a direct impact on
      global warming due to greenhouse gas emissions. Containment of this process
      requires characterizing its spatial distribution and that of the environmental
      factors related to its occurrence. The aim of this study is to investigate the
      spatial and temporal distribution of deforested areas and forest fires in the
      State of Roraima from 2000 to 2010. We mapped deforested areas and forest fires
      using Landsat images and associated their occurrence with two phytoclimatic
      zones: zone with savanna influence (ZIS), and zone without savanna influence
      (ZOS). Total deforested area during the interval was estimated at 3.06 * 10(3)
      km(2) (ZIS = 55 %; ZOS = 45 %) while total area affected by forest fires was
      estimated at 3.02 * 10(3) km(2) (ZIS = 97.7 %; ZOS = 2.3 %). Magnitude of
      deforestation in Roraima was not related to the phytoclimatic zones, but small
      deforested areas (<=17.9 ha) predominated in ZOS while larger deforestation
      classes (>17.9 ha) predominated in ZIS, which is an area with a longer history of
      human activities. The largest occurrence of forest fires was observed in the ZIS
      in years with El Nino events. Our analysis indicates that the areas most affected
      by forest fires in Roraima during 2000-2010 were associated with strong climatic
      events and the occurrence these fires was amplified in ZIS, a sensitive
      phytoclimatic zone with a higher risk of anthropogenic fires given its drier
      climate and open forest structure. 

PMID- 25604217
TI  - [Research and development of catastrophic estimation and emergency rescue
      decision support system].

PMID- 25604216
TI  - A penalized likelihood approach for investigating gene-drug interactions in
      pharmacogenetic studies.
AB  - Pharmacogenetics investigates the relationship between heritable genetic
      variation and the variation in how individuals respond to drug therapies. Often,
      gene-drug interactions play a primary role in this response, and identifying
      these effects can aid in the development of individualized treatment regimes.
      Haplotypes can hold key information in understanding the association between
      genetic variation and drug response. However, the standard approach for haplotype
      based association analysis does not directly address the research questions
      dictated by individualized medicine. A complementary post-hoc analysis is
      required, and this post-hoc analysis is usually under powered after adjusting for
      multiple comparisons and may lead to seemingly contradictory conclusions. In this
      work, we propose a penalized likelihood approach that is able to overcome the
      drawbacks of the standard approach and yield the desired personalized output. We
      demonstrate the utility of our method by applying it to the Scottish Randomized
      Trial in Ovarian Cancer. We also conducted simulation studies and showed that the
      proposed penalized method has comparable or more power than the standard approach
      and maintains low Type I error rates for both binary and quantitative drug
      responses. The largest performance gains are seen when the haplotype frequency is
      low, the difference in effect sizes are small, or the true relationship among the
      drugs is more complex. 

PMID- 25604218
TI  - [Negative fluid balance predicts survival in patients with septic shock].
AB  - OBJECTIVE: To explore the change of fluid balance in patients with septic shock
      for seven continuous days and examine its effect on clinical prognosis. METHODS:
      A retrospective study was conducted for 105 patients with septic shock admitted
      into our intensive care unit (ICU) from May 2013 to February 2014. They were
      divided into non-survivors and survivors. Their baseline data, net balance
      quantity of fluid for seven continuous days and laboratory results were recorded
      and analyzed. RESULTS: Among them, 28 patients died. Duration of mechanical
      ventilation, sequential organ failure assessment (SOFA) score and acute
      physiology and chronic health evaluation II (APACHE II) score were all lower in
      survivors than those in non-survivors (6 d vs 11 d, P = 0.002; 7 d vs 9 d, P <
      0.001; 15 vs 19, P = 0.035). Yet hospitalization time in survivors was longer
      than that in non-survivors (30 d vs 18 d, P = 0.026) . According to trend graph
      on net balance of each day, the cumulative net negative fluid balance in
      survivors increased over time while it remained stable in non-survivors. Among
      seven days, the cumulative net fluid balance at Day 7 was most negatively
      correlated with survival days (r = -0.278, P = 0.006). Logistic regression
      analysis showed that SOFA score and cumulative net balance at Day 7 were the
      independent prognostic risk factors for septic shock. Moreover, at Day 7, no
      statistically significant inter-group difference existed in serum creatinine,
      alanine aminotransferase, PO(2)/FIO(2) and cardiac troponin I levels. But serum
      total bilirubin in survivors was lower than that in non-survivors (16.0 vs 27.9,
      P = 0.031). CONCLUSION: Cumulative net negative balance quantity of fluid in
      survivors was much more than that in non-survivors. SOFA score and net balance
      quantity of fluid at Day 7 were the independent prognostic risk factors for
      septic shock. Cumulative net fluid balance at Day 7 was most negatively
      correlated with survival days. No significant inter-group difference existed in
      organ function at Day 7.

PMID- 25604219
TI  - [Sedative effects of dexmedetomidine in post-operative elder patients on
      mechanical ventilation].
AB  - OBJECTIVE: To evaluate the efficacy and safety of dexmedetomidine for post
      operative elder patients on mechanical ventilation (MV). METHODS: For this
      randomized controlled trial, 108 cases of post-operative patients on MV were
      enrolled and assigned into either dexmedetomidine group (n = 54) or propofol
      group (n = 54) for sedation. And propofol was used for rescue. The dose of
      sedation was regulated by Ramsay score for maintaining a sedative score of 3-4.
      In both groups, fentanyl was provided intravenously continually for analgesia.
      The amount of fentanyl was adjusted according to the numerical rating scale (NRS)
      score for maintaining an analgesic score of 0-3. The average Ramsay score, the
      frequency of propofol, the highest score of NRS, the total dosage of fentanyl and
      recovery time were compared. Additional outcomes included duration of mechanical
      ventilation and intensive care unit (ICU) length. And the incidence of delirium
      and cardiovascular adverse events were compared for two groups. RESULTS: No
      significant inter-group difference existed in the effectiveness of sedation.
      Compare with propofol group, the highest score of NRS decreased (1.8 +/- 1.12 vs
      3.1 +/- 1.24, P < 0.05), the total dosage of fentanyl significantly decreased
      (427.6 +/- 14.1 vs 658.4 +/- 27.3 ug, P < 0.05) and recovery time became
      significantly shortened (0.3 +/- 0.02 h vs 1.1 +/- 0.3 h, P < 0.05) in
      dexmedetomidine group. Median duration of mechanical ventilation in
      dexmedetomidine group (21.0 h, 95%CI: 18.6-21.4 h) was significantly shorter than
      that in propofol group (28.0 h, 95%CI: 25.6-30.4 h) (P < 0.05). No inter-group
      differences existed in the ICU length of stay and the incidence of delirium. Two
      cases in dexmedetomidine group developed bradycardia while hypotension occurred
      in two cases of propofol group. CONCLUSION: Sedative effects of dexmedetomidine
      are safe and effective for post-operative elder patients on MV. And it offers a
      better efficacy of analgesia and shorter durations of MV and recovery time. But
      dexmedetomidine had no significant influence on the ICU length of stay or the
      incidence of delirium.

PMID- 25604220
TI  - [Effects of losartan on pulmonary dendritic cells in lipopolysaccharide- induced
      acute lung injury mice].
AB  - OBJECTIVE: To assess the effects of losartan on the frequency and phenotype of
      respiratory dendritic cells (DC) in lipopolysaccharide (LPS)-induced acute lung
      injury (ALI) mice. METHODS: The C57BL/6 mice were randomly divided into 3 groups
      of control, ALI and ALI+losartan. ALI animals received 2 mg/kg of LPS;
      ALI+losartan animals 2 mg/kg of LPS and 15 mg/kg of losartan 30 min before an
      intratracheal injection of LPS; control animals phosphate buffer saline (PBS)
      instead of LPS. Lung wet weight/body weight (LW/BW) was recorded to assess lung
      injury. The pathological changes were examined under optical microscope. The
      frequency and phenotype of pulmonary DC were characterized by flow cytometry.
      Meanwhile, the levels of IL-6 in lung homogenates were assessed by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: (1) The LPS-induced rise in LW/BW was
      partially prevented by a pretreatment of losartan. (2) Histologically, widespread
      alveolar wall thickening caused by edema, severe hemorrhage in interstitium and
      alveolus and marked and diffuse interstitial infiltration of inflammatory cells
      were observed in the ALI group. Whereas, losartan effectively attenuated the LPS
      induced pulmonary hemorrhage, leukocytic infiltration in interstitium and
      alveolus. (3) Meanwhile, the levels of IL-6 in lung tissue were significantly
      enhanced in the LPS-induced ALI mice. Yet after a pretreatment of losartan, the
      pulmonary level of IL-6 markedly decreased. (4) LPS dosing resulted in a rapid
      accumulation of DC in lung tissues and an up-regulated expression of CD80 in LPS
      induced ALI. In contrast, the expression of MHC II on respiratory DC was not
      significantly different among groups. A pretreatment of losartan led to a marked
      reduction in CD80 expression on pulmonary DC (P < 0.05 vs ALI). CONCLUSION:
      Losartan may down-regulate pulmonary injury by inhibiting the activation of
      pulmonary DC.

PMID- 25604221
TI  - [Severity analyese of acute pancreatitis based on etiology].
AB  - OBJECTIVE: To explore the relationship between etiology and severity of acute
      pancreatitis (AP). METHODS: A total of 486 AP patients, hospitalized at
      digestive, general surgery or critical care medicine departments from May 2012 to
      May 2014, were recruited retrospectively. And the data of clinical features,
      etiology and severity classification of AP according to the revised Atlanta
      criteria (2012) were collected. The relationships between different gender, age
      group, etiology and severity of disease were compared. RESULTS: The etiology
      distribution was as follows: gallstone (n = 296, 60.9%), hyperlipidemia (n = 93,
      19.1%), alcohol (n = 48, 9.9%) and other causes (n = 49, 10.1%). And the severity
      was mild AP (MAP, n = 387, 79.6%), moderate-severe AP (MSAP, n = 53, 10.9%) and
      severe AP (SAP, n = 46, 9.5%). The proportion of females for gallstone AP was
      slightly higher than that of males (1.23: 1). However, for hyperlipidemic and
      alcoholic AP, the proportion of males was significantly higher than that of
      females (P = 0.00). The onset age of gallstone AP was generally over 40 years
      while hyperlipidemic and alcoholic AP tended to occur in patients aged under 60
      years (P = 0.00). Among all age groups, the group of over 60 years had the
      highest MSAP incidence of 14% while <40-year-old group the highest incidence of
      SAP at 11.3%. And the >60-year-old group had the highest total incidence of MSAP
      and SAP at 22.2%. Compared with gallstone, alcohol and other causes,
      hyperlipidemic AP had a higher risk of MSAP and SAP (P = 0.028). CONCLUSION:
      Gallstone remains a leading cause of AP. Hyperlipidemic pancreatitis has shown a
      rising tendency in recent years and it often result in a more serious clinical
      process. And the clinicians should pay more attention to health education of
      patients.

PMID- 25604222
TI  - [A study of autonomic dysfunction and sympathetic skin response in motor neuron
      disease].
AB  - OBJECTIVE: To explore the symptoms of autonomic dysfunction and sympathetic skin
      response (SSR) abnormality in patients of motor neuron disease (MND). METHODS:
      The clinical features of autonomic dysfunction were collected as follows: dermal
      numbness or pruritus, parahidrosis, xerostomia, salivation, abnormal skin
      temperature, orthostatic hypotension, mydriasis, ptosis or abnormal pupillary
      light reflex, constipation, voiding dysfunction and sexual dysfunction. SSR was
      performed and the results were judged according to the normal range of our
      laboratory. Abnormality rate in MND patients was calculated. The relationship
      between clinical symptoms and SSR parameters were analyzed statistically.
      RESULTS: Among a total of 142 MND patients, the symptom incidences of autonomic
      dysfunction were as follows: dermal numbness (53.5%), dermal pruritus (15.5%),
      parahidrosis (10.6%), xerostomia (9.1%), salivation (2.1%), abnormal skin
      temperature (14.8%), orthostatic hypotension (2.1%), constipation (16.2%),
      voiding dysfunction (9.9%) and sexual dysfunction (1.4%). Abnormal SSR was found
      in 51/142 (35.9%) patients, including 12(8.5%) in palmar and 47(33.1%) in
      plantar. The features of abnormal SSR included delayed latency of palmar (P <
      0.05) and decreased amplitudes of both palmar and plantar compared with normal
      ranges (P < 0.01 respectively). The group of patients with lumbosacral onset had
      a higher abnormal rate of SSR than those of other onset sites. There was no
      significant correlation between clinical symptoms and abnormal SSR parameters.
      CONCLUSION: The patients of MND exhibit autonomic dysfunctions of skin, gland
      secretion, cardiovascular system and sphincters. Some of them show abnormal SSR
      with prolonged latency and decreased amplitude. The abnormalities of SSR are not
      related to clinical features of autonomic dysfunction. Those with an onset of
      lower limbs have a higher rate of abnormal SSR.

PMID- 25604223
TI  - [Longitudinally extensive spinal cord lesion: etiology and imaging features].
AB  - OBJECTIVE: To explore the etiologies and imaging features of longitudinally
      extensive spinal cord lesion (LESCL). METHODS: The etiologies and magnetic
      resonance (MR) imaging features of 51 hospitalized LESCL patients from January
      2011 to August 2013 were reviewed and retrospectively analyzed. RESULTS: Among
      them, the causes were neuromyelitis optica spectrum disorder (NMOSD, n = 25),
      isolated longitudinally extensive transverse myelitis (n = 6), subacute combined
      degeneration (n = 4), multiple sclerosis (MS, n = 3), paraneoplastic myelopathy
      (n = 3), anterior spinal artery syndrome (n = 3), acute disseminated
      encephalomyelitis (n = 2), spinal dural arteriovenous fistula (n = 2),
      intramedullary spinal cord metastasis (n = 1), myelopathic leukemia (n = 1) and
      syringomyelus (n = 1). For MR imaging, at least one lesion of each patient
      presented continuously longitudinal profile and whole-length spinal cord was
      involved in 11 patients. CONCLUSION: LESCL may be caused by various diseases. And
      the imaging features may aid its diagnosis despite a lack of specificity.

PMID- 25604224
TI  - [Application of multi-voxel proton magnetic resonance spectroscopy in different
      hippocampal regions of normal cognitive people].
AB  - OBJECTIVE: To explore the reproducible metabolic test and gender difference and
      investigate the distribution rules of metabolite concentration in different
      hippocampal regions (head, body and tail) of normal cognitive people for
      elucidating the pathological metabolic changes. METHODS: The hippocampal multi
      voxel proton spectroscopy of 24 normal cognitive young volunteers scanned by a
      3.0 T magnetic resonance (MR). Every volunteer was scanned thrice. The data was
      processed by MR post-processing workstation. The hippocampus was divided into
      three parts (head, body and tail) and the ratios of N-acetylaspartate
      (NAA)/creatine (Cr), myoinositol (MI)/Cr, MI/NAA and choline (Cho)/Cr were
      calculated separately. We compared the metabolic ratios of each region of
      bilateral hippocampi between male and female groups and three different tests,
      also analyzed the distribution rule of each metabolite along the long axis of
      hippocampus. RESULTS: The metabolic ratio (NAA/Cr, MI/Cr, MI/NAA and Cho/Cr) of
      each region of bilateral hippocampi between male and female groups and among
      three tests showed no statistical differences. NAA/Cr gradually rose (P < 0.05)
      while MI/NAA and Cho/Cr gradually declining from bilateral hippocampal head to
      tail (P < 0.05). MI/Cr gradually declined from bilateral hippocampal head to
      tail, but there was statistical difference only between right hippocampal head
      and tail (P < 0.05). CONCLUSION: The hippocampal multi-voxel proton spectroscopy
      is technically stable. There is no gender difference. And distribution
      differences and metabolite concentration trends exist along hippocampal head,
      body and tail.

PMID- 25604226
TI  - [Imaging origins and characteristics analysis of acute and chronic aspiration
      pneumonia].
AB  - OBJECTIVE: To discuss about the pathologic and imaging origins and
      characteristics of CT scaning and X-ray radiography for acute and chronic
      aspiration pneumonia. METHODS: Imaging data from 30 patients with aspiration
      pneumonia were retrospectively analyzed, CT scaning was performed in 27 patients,
      which PMVR reconstruction was performed in 21 cases;3 exammed by X-ray with 2
      used by esophagography. RESULTS: Opaque bodies were detected in trachea by CT
      scaning in 12 patients.7 patients in acute phase rapidly developed into acute
      respiratory distress syndrome(ARDS). CT signs of 30 patients with acute and
      chronic aspiration pneumonia included: centrilobular nodules were detected in 2
      cases with acute phase, 4 cases with subacute phase and 4 cases with chronic
      phase; the imaging of ground glass opacity were detected in 9 cases with acute
      phase, 2 cases with subacute phase and 3 cases with chronic phase; the imaging of
      bronchiectasis was detected in 8 cases with chronic phase, which mucilage
      embolism was detected in 3 of 8 cases; the imaging of atelectasis was detected in
      6 cases with chronic phase; the imaging of sheeted consolidation was detected in
      5 cases with chronic phase, 8 case with acute phase; the imaging of interstitial
      fibrosis was detected in 3 cases with chronic phase. Lesions of inferior lobe of
      right lung were detected in 9 cases with chronic phase, 4 cases with subacute
      phase, 11 case with acute phase;lesions of inferior lobe of left lung were
      detected in 6 cases with chronic phase and 3 cases with subacute group, 11 case
      with acute phase. CONCLUSION: The imaging features of acute and chronic
      aspiration pneumonia overlap with GGO and centrilobular nodules in every group.
      While the imaging features of atelectasis, bronchiectasis or mucilage embolism
      are found in chronic phase. The chest CT scaning may accurately evaluate the
      dynamic change of aspiration pneumonia.

PMID- 25604225
TI  - [Analyses of risk factors for postoperative recurrence after curative resection
      of stage III A-N2 non-small cell lung cancer].
AB  - OBJECTIVE: To explore the patterns of mediastinal lymph node metastases and
      prognostic factors of recurrence in patients undergoing curative resection of
      stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A total of 92 patients
      underwent curative operation and pathologically diagnosed as stage IIIA-N2 NSCLC
      were retrospectively reviewed. The clinicopathological data were compared between
      the recurrence and non-recurrence groups. And the potential prognostic factors
      were included for multivariate analysis using Cox proportional hazard model.
      RESULTS: The 3 and 5-year recurrence rates were 61.0% and 70.2% respectively. For
      univariate analysis, the prognostic factors were number of metastatic lymph
      nodes, positive lymph node ratio, number of metastatic mediastinal lymph nodes
      (MLN), positive MLN ratio, number of MLN metastasis > 3, multiple station
      metastasis, trans-regional metastasis and multi-zonal metastasis. A multivariate
      analysis using Cox regression identified 2 independent factors of prognosis:
      trans-regional MLN metastasis (P = 0.035) and number of MLN metastasis >3 (P =
      0.045). The recurrence risk of patients with trans-regional MLN metastasis was
      2.0 times higher than those with regional MLN metastasis while the recurrence
      risk of patients with number of MLN metastasis >3 was 2.2 times higher than those
      with number of MLN metastasis of 1-3. CONCLUSION: Recurrence risk of stage IIIA
      N2 non-small cell lung cancer (NSCLC) after curative resection may be estimated
      by location and number of MLN metastasis. And the subgroup with trans-regional
      MLN metastasis and number of MLN metastasis >3 carries the highest risk of
      recurrence.

PMID- 25604227
TI  - [Treatment of fixed atlantoaxial dislocation and basilar invagination with C1-2
      screw and rod reduction and fixation technique].
AB  - OBJECTIVE: To introduce a novel technique of reducing fixed atlantoaxial
      dislocation (FAAD) and basilar invagination (BI) with C1-C2 screw and rod system.
      METHODS: From January 2009 to December 2011, 26 patients of FAAD and BI were
      reduced successfully with an insertion of C1 lateral mass and C2 pedicle/pars
      screw and rod system. The cohort had 17 females and 9 males. And their most
      common presenting symptoms were extremity muscle weakness, restricted neck
      movement and paresthesia. RESULTS: All of them achieved effective reduction.
      Among them, 18 attained complete reduction and 8 partial reduction (over 60%
      extent of reduction). The mean atlanto-dental interval (ADI) value was 2.1 mm
      postoperatively versus 8.8 mm preoperatively (t = 21.1, P < 0.01) . All of them
      had relieved compression of dura and medulla oblongata and cervical cord. All
      clinical symptoms improved. One case had pulmonary infection while another case
      delayed healing of incision. Both recovered well after symptomatic treatments.
      Bony fusion reached 100% during a mean follow-up period of 22 months. CONCLUSION:
      The C1-C2 screw and rod system may achieve effective reduction and fixation for
      FAAD and BI. Capable of preserving atlanto-occipital joints in patients without
      atlas assimilation, this procedure provide more solid immobilization than
      occipitocervical fusion in those with atlas assimilation.

PMID- 25604228
TI  - [Prevalence of maternal near miss and adverse pregnancy outcomes in Zhejiang
      province].
AB  - OBJECTIVE: To explore the prevalence of maternal near miss (MNM) and adverse
      pregnancy outcomes in Zhejiang province by MNM surveillance system. METHODS: A
      cross-sectional study was conducted during 2012 and 2013. All MNM cases were
      recruited from the MNM surveillance system. The information was reported by
      direct network report system, including personal information, obstetric
      complications, maternal rescue measures, rescue process and severe maternal and
      perinatal outcomes. RESULTS: A total of 826 MNM patients were recruited. The MNM
      rate was 5.6 cases/1 000 live births (LB). Maternal gestational hypertension was
      the most common disease among MNM, accounting for 19.9% (n = 164) . The second
      prevalent one was insufficient uterine contraction, accounting for 19.6% (n =
      162). Placenta previa was the third one accounting for 17.7% (n = 146). Among
      adverse pregnancy outcomes, 139 cases underwent hysterectomy (n = 139, 16.8%).
      There were 81 perinatal deaths with a perinatal mortality of 10.4%. And 279 cases
      (39.9%) were preterm. CONCLUSION: MNM surveillance system is valuable for
      grasping the prevalence of MNM. And it helps to reduce MNM rate by improving the
      quality of obstetrics and lower the preterm rate and perinatal mortality.

PMID- 25604229
TI  - [Impact of different luteal support methods on clinical outcomes of frozen-thawed
      embryo transfer cycles].
AB  - OBJECTIVE: To determine whether luteal support of dydrogesterone may enhance the
      outcome of frozen-thawed embryo transfer (FET) in natural cycles by comparing the
      FET outcomes of different luteal support methods. METHODS: A total of 2 248
      natural FET cycles with an endometrial thickness of 8-12 mm and type A on
      ovulation day, from January 2011 to March 2013 were chosen. Oral dydrogesterone
      (n = 1 967) or intramuscular progesterone (n = 281) was used for luteal support.
      The rates of clinical pregnancy, implantation, ectopic pregnancy, miscarriage and
      live birth were compared among these groups. RESULTS: The patients receiving oral
      dydrogesterone or intramuscular progesterone had similar profiles of age, type of
      infertility, endometrial thickness and average numbers of embryo transfer. The
      dydrogesterone group had higher rates of clinical pregnancy (43.26% vs 38.79%)
      and implantation (25.76% vs 21.13%). However a lower miscarriage rate (17.27% vs
      22.02%) was insignificant. The rates of ectopic pregnancy, premature birth and
      live birth were also similar. When infertile factors were considered, the
      dydrogesterone group had significantly higher clinical pregnancy rates (43.78% vs
      34.38%, P < 0.05), lowered miscarriage rates (16.54% vs 29.55%, P < 0.05) and
      increased live birth rates (34.16% vs 23.44%, P < 0.05) among simple tubal factor
      patients. CONCLUSION: Oral administration of dydrogesterone for luteal support
      offers more advantages in natural cycle FET than intramuscular progesterone,
      especially for simple tubal factor infertility.

PMID- 25604230
TI  - [Clinical features, treatment and follow-ups of childhood systemic lupus
      erythematosus].
AB  - OBJECTIVE: To summarize the characteristics of clinical features, laboratory
      tests, treatments and outcomes of childhood systemic lupus erythematosus (SLE).
      METHODS: A retrospective study was conducted for 130 cases of first-confirmed
      childhood SLE hospitalized from 2001 to 2008. Their clinical data of initial
      manifestations, system involvements, laboratory tests, treatments and outcomes
      were recorded and analyzed. Among them, there were 25 males and 105 females with
      a gender ratio of 1: 4.2. The youngest was 4 years old and the oldest 16 years
      old. And the mean age of onset was 11.5 +/- 2.2 years. RESULTS: The initial
      manifestations included fever (66%), rash (62.33%) and fatigue (47.33%). And the
      cutaneous-mucosal system (80%), hematological system (70.77%) and kidney (66.15%)
      were frequently involved. Anemia (64.62%) and urine protein positivity (66.15%)
      were the most common abnormalities. All patients had positive ANA. The positive
      rate of anti-dsDNA was 88.37%. Six patients had antiphospholipid syndrome (APS).
      The levels of IgM-aCL and IgM-anti-beta(2)-GP-Iwere moderately or higher
      positive. Glucocorticoid was the first-line medication. All patients took
      steroids. Different immunodepressants were also used depending on the severity of
      illness. The effective rates of one month and one year were 80.7% and 95.1%
      respectively. Six patients died. CONCLUSION: The patients with serious organ
      involvements as the initial manifestations end to have a worse prognosis.
      Cutaneous-mucosal system, hematological system and kidney are the most frequently
      involved. Most patients have a high level of ANA titer. IgM-aCL and IgM-anti
      beta(2)-GP-Iare sensitive for diagnosing antiphospholipid syndrome. Early
      diagnosis, appropriate treatment and regular follow-ups may help to improve the
      clinical prognosis of SLE.

PMID- 25604231
TI  - [Computed tomograph findings of tissue adjacent to thoracic vertebrae involved by
      IgG4-related disease].
AB  - OBJECTIVE: To evaluate the computed tomograph (CT) findings of IgG4-related
      disease (RD) involving soft tissue adjacent to thoracic vertebrae. METHODS: The
      chest and abdomen CT findings of 22 cases of IgG4-RD proved by orbital pathology
      and/or laboratory examination were retrospectively reviewed. The CT findings of
      paravertebral soft tissue in posterior mediastinum and the corresponding follow
      up after therapy were primarily observed. RESULTS: Among them, there were 8 males
      and 2 females with an average age of 57.6 (42-70) years. CT showed diffuse
      thickening of soft tissue in thoracic paravertebral space forming a crescent
      shaped mass encasing bilateral thoracic vertebrae without abnormal bone change.
      There was consistent inhomogeneous density of paravertebral adipose tissue
      adjacent to paravertebral mass lesion with multiple dilated vessels joining
      azygos vein or vena hemiazygos finally. Other abnormalities were as follows:
      multiple lymphadenopathy of neck, mediastinum and/or retroperitoneal space (n =
      10), interstitial pneumonitis (n = 4), diffuse pancreatic thickening (n = 2) and
      slightly hypodense soft tissue shadow with a hazy border of retroperitoneal space
      (n = 8). On follow-up CTs, there was marked relief after regular therapy in 4
      cases. CONCLUSION: The thoracic paravertebrae space is commonly involved by IgG4
      RD. And it occurs frequently in senile males. The characteristic CT feature is
      diffuse thickening of soft tissue with multiple prominent bands in adjacent
      thoracic paravertebral space.

PMID- 25604232
TI  - [Application of double-tagging in monitoring of tumorigenesis and tracking of
      mesenchymal stem cells in mice].
AB  - OBJECTIVE: To establish murine liver cancer cell line (Hepa1-6) and human
      mesenchymal stem cells (hMSCs) with dual-modality imaging lentiviral vector
      transfection and monitor the development of liver tumors and dynamically tracking
      of hMSCs by bioluminescent imaging in vivo. METHODS: The cell lines of Hepa 1-6
      and hMSCs were constructed abd tranfected with RL-eGFP and FL2-mKate2
      lentiviruses respectively. Then the eGFP(+)-Hepa1-6 and mKate2(+)-hMSCs cell
      lines were selected by fluorescence activated cell sorting (FACS). The
      bioluminescent imaging technology was employed to evaluate their bioluminescent
      abilities in vitro and in vivo. And the capacity of mKate2(+)-hMSCs migrating to
      HCC cell line (eGFP(+)-Hepa1-6) was evaluated by Transwell migration assay.
      RESULTS: DNA sequencing analysis confirmed that gene sequences of lentiviral
      vectors were correct without mutation. We successfully constructed the lentivirus
      vector, produced lentivirus and infected Hepa1-6 and hMSCs respectively.
      Subsequently eGFP(+)-Hepa1-6 cells and mKate2(+)-hMSCs were obtained by FACS. The
      expressions of fluorescent protein eGFP and mKate were confirmed by fluorescence
      microscope. By bioluminescent imaging system, bioluminescence intensity strongly
      correlated with cell number. The Transwell assay showed that hMSCs migrated
      toward heptocellular carcinoma (HCC) cells. CONCLUSION: A lentivirus vector has
      been successfully constructed for infecting Hepa1-6 and hMSCs and analyzed by
      fluorescence and bioluminescent imaging. And that makes it technically feasible
      to further monitor the interaction of hMSCs and liver tumor cells. These results
      provide rationales for further studying the mechanism of MSCs in the development
      and progression of HCC.

PMID- 25604233
TI  - [Changes of ubiquitin-proteasome system in human umbilical vein endothelial cells
      induced by oxidative low density lipoprotein].
AB  - OBJECTIVE: To explore the role of ubiquitin-proteasome system (UPS) in the injury
      of human umbilical vein endothelial cells (HUVECs) induced by oxidative low
      density lipoprotein (ox-LDL). METHODS: After exposure to ox-LDL, the levels of
      ubiquitin (Ub), E1 (ubiquitin activation enzyme), E2 (ubiquitin conjugating
      enzymes) and E3 (ubiquitin protein ligating enzymes) were detected by Western
      blot. RESULTS: The levels of Ub, E1, E2 and E3 were up-regulated after induced by
      ox-LDL (grey level: 0.46 +/- 0.08 vs 0.25 +/- 0.09; 0.63 +/- 0.09 vs 0.45 +/-
      0.09; 0.49 +/- 0.07 vs 0.35 +/- 0.06; 0.67 +/- 0.05 vs 0.45 +/- 0.05; ox-LDL 100
      ug/ml, P < 0.05). The regulations peaked at 12 h and 24 h (12 h grey level: 0.58
      +/- 0.08 vs 0.25 +/- 0.09; 0.72 +/- 0.08 vs 0.45 +/- 0.08; 0.65 +/- 0.10 vs 0.35
      +/- 0.06; 0.65 +/- 0.05 vs 0.43 +/- 0.05, P < 0.05; 24h grey level: 0.72 +/- 0.08
      vs 0.25 +/- 0.09; 0.79 +/- 0.08 vs 0.45 +/- 0.08; 0.72 +/- 0.04 vs 0.35 +/- 0.06;
      0.65 +/- 0.05 vs 0.43 +/- 0.05, P < 0.05). CONCLUSION: The treatment of ox-LDL
      may activate the UPS to promote the degradation of HUVECs.

PMID- 25604234
TI  - [Primary fabrication of a tissue-engineered mesh for pelvic floor reconstruction
      and research in vivo].
AB  - OBJECTIVE: To explore the fabrication of a tissue-engineered mesh fabricated with
      autologous adipose-derived mesenchymal stem cells (ADSC) and silk fibroin
      scaffold for female pelvic reconstruction. METHODS: Sprague-Dawley rat adipose
      tissue was obtained from inguinal region. Mesenchymal stem cells were isolated
      and proliferated in vitro. The sericin of silk was removed after knitting in to
      web. Then a compound scaffold freeze-dried of silk fibroin web and silk fibroin
      solution was prepared for ADSC seeding. after 1-week culturing, the cellular
      morphology and extracellular matrix secretion on scaffold were observed by
      scanning electronic microscopy. The tissue-engineered meshes were implanted
      subcutaneously into the homologous rats while silk fibroin scaffolds served as
      control. Then the biomechanics, collagen matrix and local tissue response to
      tissue-engineered meshes in vivo with that to silk fibroin scaffolds were
      estimated. RESULTS: ADSC were fibroblast-like and proliferated well in vitro. SEM
      showed that the scaffold had an interwoven structure with a smooth surface and
      the silk sponges in scaffold had a uniform and porous structure. ADSC adhered
      firmly to the scaffold, secreted extracellular matrix and formed cell sheets on
      scaffold. In vivo studies showed that the tissue matrix of tissue-engineered
      meshes was better organized than silk fibroin scaffolds. They also had higher
      failure force (3.081 +/- 0.121 vs 2.167 +/- 0.148 N) and Young's modulus (3.191
      +/- 0.146 vs 2.263 +/- 0.213 MPa) and more collagen content (18.648 +/- 0.867 vs
      14.123 +/- 0.989 ug/mg) than silk fibroin scaffolds (P < 0.05). CONCLUSION: As a
      suitable cell type for tissue engineering, ADSC may be successfully isolated and
      stably proliferated in vitro. The tissue-engineered meshes have an excellent
      biocompatibility and appropriate properties for pelvic floor reconstruction.

PMID- 25604235
TI  - Probing post-synthetic metallation in metal-organic frameworks: insights from X
      ray crystallography.
AB  - For post-synthetic metallation (PSMet) of a metal-organic framework (MOF,
      [Mn3(L2)(L')] = 1) we show a solvent dependency for the form of the metallated
      product. PSMet of 1 with MnCl2 in ethanol leads to a single metal entity per
      coordinating site while acetonitrile yields a remarkably complex multiply
      metallated product; thus, determining the extent of metallation requires an
      intimate understanding of the chemistry occurring in the MOF pores.

PMID- 25604236
TI  - Using the pathogenic and nonpathogenic nonhuman primate model for studying non
      AIDS comorbidities.
AB  - With the advent of antiretroviral therapy that can control virus replication
      below the detection levels of conventional assays, a new clinical landscape of
      AIDS emerged, in which non-AIDS complications prevail over AIDS-defining
      conditions. These comorbidities are diverse and affect multiple organs, thus
      resulting in cardiovascular, kidney, neurocognitive and liver disease,
      osteopenia/osteoporosis, and cancers. A common feature of these conditions is
      that they are generally associated with accelerated aging. The mechanism behind
      these comorbidities is chronic excessive inflammation induced by HIV infection,
      which persists under antiretroviral therapy. Progressive simian immunodeficiency
      virus (SIV) infection of nonhuman primates (NHPs) closely reproduces these
      comorbidities and offers a simplified system in which most of the traditional
      human risk factors for comorbidities (i.e., smoking, hyperlipidemia) are absent.
      Additionally, experimental conditions can be properly controlled during a shorter
      course of disease for SIV infection. As such, NHPs can be employed to
      characterize new paradigms of AIDS pathogenesis and to test the efficacy of
      interventions aimed at alleviating non-AIDS-related comorbidities. 

PMID- 25604237
TI  - Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated
      neurocognitive disorder (HAND).
AB  - Early in the HIV epidemic, the central nervous system (CNS) was recognized as a
      target of infection and injury in the advanced stages of disease. Though the most
      severe forms of HIV-associated neurocognitive disorder (HAND) related to severe
      immunosuppression are rare in the current era of widespread combination
      antiretroviral therapy (cART), evidence now supports pathological involvement of
      the CNS throughout the course of infection. Recent work suggests that the stage
      for HIV neuropathogenesis may be set with initial viral entry into the CNS,
      followed by initiation of pathogenetic processes including neuroinflammation and
      neurotoxicity, and establishment of local, compartmentalized HIV replication that
      may reflect a tissue reservoir for HIV. Key questions still exist as to when HIV
      establishes local infection in the CNS, which CNS cells are the primary targets
      of HIV, and what mechanistic processes underlie the injury to neurons that
      produce clinical symptoms of HAND. Advances in these areas will provide
      opportunities for improved treatment of patients with established HAND,
      prevention of neurological disease in those with early stage infection, and
      understanding of HIV tissue reservoirs that will aid efforts at HIV eradication. 

PMID- 25604238
TI  - ocsESTdb: a database of oil crop seed EST sequences for comparative analysis and
      investigation of a global metabolic network and oil accumulation metabolism.
AB  - BACKGROUND: Oil crop seeds are important sources of fatty acids (FAs) for human
      and animal nutrition. Despite their importance, there is a lack of an essential
      bioinformatics resource on gene transcription of oil crops from a comparative
      perspective. In this study, we developed ocsESTdb, the first database of
      expressed sequence tag (EST) information on seeds of four large-scale oil crops
      with an emphasis on global metabolic networks and oil accumulation metabolism
      that target the involved unigenes. DESCRIPTION: A total of 248,522 ESTs and
      106,835 unigenes were collected from the cDNA libraries of rapeseed (Brassica
      napus), soybean (Glycine max), sesame (Sesamum indicum) and peanut (Arachis
      hypogaea). These unigenes were annotated by a sequence similarity search against
      databases including TAIR, NR protein database, Gene Ontology, COG, Swiss-Prot,
      TrEMBL and Kyoto Encyclopedia of Genes and Genomes (KEGG). Five genome-scale
      metabolic networks that contain different numbers of metabolites and gene-enzyme
      reaction-association entries were analysed and constructed using Cytoscape and
      yEd programs. Details of unigene entries, deduced amino acid sequences and
      putative annotation are available from our database to browse, search and
      download. Intuitive and graphical representations of EST/unigene sequences,
      functional annotations, metabolic pathways and metabolic networks are also
      available. ocsESTdb will be updated regularly and can be freely accessed at
      http://ocri-genomics.org/ocsESTdb/ . CONCLUSION: ocsESTdb may serve as a valuable
      and unique resource for comparative analysis of acyl lipid synthesis and
      metabolism in oilseed plants. It also may provide vital insights into improving
      oil content in seeds of oil crop species by transcriptional reconstruction of the
      metabolic network.

PMID- 25604239
TI  - Highly Sensitive and Selective Field-Effect-Transistor NonEnzyme Dopamine Sensors
      Based on Pt/Conducting Polymer Hybrid Nanoparticles.
AB  - Dopamine (DA), as one of catecholamine family of neurotransmitters, is crucially
      important in humans owing to various critical effects on biometric system such as
      brine circuitry, neuronal plasticity, organization of stress responses, and
      control of cardiovascular and renal organizations. Abnormal level of dopamine in
      the central nervous system causes several neurological diseases, e.g.,
      schizophrenia, Parkinson's disease, and attention deficit hybperactivity disorder
      (ADHD)/attention deficit disorder (ADD). In this report, we suggest the
      fabrication of nonenzyme field effect transistor (FET) sensor composed of
      immobilized Pt particle decorated conducting-polymer (3-carboxylate polypyrrole)
      nanoparticles (Pt_CPPy) to detect dopamine. The hybrid nanoparticles (NPs) are
      produced by means of facile chemical reduction of pristine CPPyNP-contained Pt
      precursor (PtCl4 ) solution. The Pt_CPPys are then immobilized on an amine
      functionalized (-NH2 ) interdigitated-array electrode substrate, through the
      formation of covalent bonds with amine groups (-CONH). The resulting Pt_CPPy
      based FET sensors exhibit high sensitivity and selectivity toward DA at
      unprecedentedly low concentrations (100 * 10(-15) m) and among interfering
      biomolecules, respectively. Additionally, due to the covalent bonding involved in
      the immobilization process, a longer lifetime is expected for the FET sensor. 

PMID- 25604240
TI  - Alkylidene malonates and alpha,beta-unsaturated alpha'-hydroxyketones as
      practical substrates for vinylogous Friedel-Crafts alkylations in water catalysed
      by scandium(III) triflate/SDS.
AB  - Alkylidene malonates and alpha,beta-unsaturated alpha'-hydroxyketones are
      demonstrated to be efficient classes of electrophiles for the scandium(III)
      triflate/sodium dodecyl sulphate (SDS) catalysed vinylogous Friedel-Crafts
      alkylation of indoles and pyrroles in water. These substrates contain an easily
      removable auxiliary group that increases affinity for the catalytic metal ion in
      such a way that they can compete with water for binding to the catalytic metal
      ion. Thus, alkylidene malonates and alpha,beta-unsaturated alpha'-hydroxyketones
      are attractive substitutes for, e.g., alpha,beta-unsaturated carboxylic acids and
      -esters, which in aqueous media are not reactive enough in these reactions. The
      combination of Lewis acid and SDS in catalysis results in considerable
      acceleration of the reaction in water compared to organic solvents. The method
      presented is attractive because the reactions are fast, experimentally
      straightforward and give rise to high yields of products.

PMID- 25604241
TI  - Late posterior segment relapses in a series of Vogt-Koyanagi-Harada disease.

PMID- 25604243
TI  - High-Throughput Screening Assay for the Identification of Compounds Enhancing
      Collagenous Extracellular Matrix Production by ATDC5 Cells.
AB  - Extracellular matrix (ECM) provides not only structural support to the cells but
      also signals that regulate their fate. In many tissue engineering approaches, it
      remains challenging to achieve the right amount and type of ECM secreted by the
      cells to faithfully mimic the native tissue. In this article, we describe how to
      design and perform a high-throughput assay to screen for molecules capable of
      enhancing collagenous ECM (cECM) production. We chose ATDC5 cells to validate the
      assay since we want to use this chondrogenic cell line later for tissue
      engineering of hypertrophic cartilage. We used a fluorescently labeled collagen
      binding probe to quantify total collagen content in ATDC5 cultures. The
      LOPAC(1280) library of pharmaceutically active compounds was screened using
      insulin (a known inducer of cECM in ATDC5 cells) as positive control. After
      screening and validation, the small-molecule tetradecylthioacetic acid (TTA) was
      shown to enhance cECM production by ATDC5 cells at both gene expression and
      protein level. Moreover, when combined with insulin, TTA showed a synergistic
      effect on cECM production. In contrast, exposure of human primary chondrocytes
      and human mesenchymal stromal cells to TTA did not induce cECM secretion. In
      conclusion, we have developed an HTS assay to screen for compounds capable of
      enhancing cECM production and discovered TTA as a potent enhancer of cECM
      secretion by ATDC5 cells. 

PMID- 25604242
TI  - Salivary cytokines as a minimally-invasive measure of immune functioning in young
      children: correlates of individual differences and sensitivity to laboratory
      stress.
AB  - There is growing interest in minimally-invasive measures of environmentally
      responsive biological systems in developmental science. Contributing to that
      endeavor, this study explores the intercorrelations, correlates, and task
      sensitivity of proinflammatory salivary cytokines in childhood. Saliva was
      sampled from 125 healthy five-year old children (49% male) across a series of
      cognitive and emotional challenge laboratory tasks. Samples were assayed for
      cytokines (IL-1beta, IL-6, IL-8, TNFalpha), and markers of hypothalamic-pituitary
      adrenal (HPA) and autonomic nervous system (ANS) activation (salivary cortisol
      and alpha-amylase [sAA]). Cytokines were positively intercorrelated and task
      sensitivity varied. Except IL-8, cytokines were elevated in children with oral
      health issues and tobacco smoke exposure. Among boys, cytokines were positively
      related to sAA and negatively related to cortisol. The findings suggest that in
      healthy children, salivary cytokine levels reflect compartmentalized oral immune
      activity. Associations between ANS and HPA activity and cytokines in saliva may
      present opportunities for minimally-invasive methods to explore neuroendocrine
      immune interactions during development.

PMID- 25604244
TI  - TTP mediates cisplatin-induced apoptosis of head and neck cancer cells by down
      regulating the expression of Bcl-2.
AB  - The chemotherapeutic agent cisplatin is widely used for treatment of head and
      neck squamous cell carcinoma (HNSCC). B-cell lymphoma 2 (Bcl-2) is an anti
      apoptotic protein that is overexpressed in cancer cells and confers resistance to
      cisplatin. Thus, inhibition of Bcl-2 expression may enhance the cisplatin
      sensitivity of cancer cells. In this study, we report that the AU-rich element
      (ARE) binding protein tristetraprolin (TTP) inhibits the expression of Bcl-2 and
      enhances cisplatin sensitivity of HNSCC cells. Cisplatin-sensitive HNSCC cells
      express high levels of TTP and low levels of Bcl-2, while cisplatin-resistant
      HNSCC cells have low levels of TTP and high levels of Bcl-2. Inhibition of TTP
      expression using siRNA increases levels of Bcl-2 and decreases cisplatin
      sensitivity in HNSCC cells. On the contrary, overexpression of TTP decreases Bcl
      2 expression and increases sensitivity to cisplatin. Together, the results of the
      present study suggest that TTP expression enhances cisplatin sensitivity in HNSCC
      cells by reducing levels of Bcl-2. 

PMID- 25604245
TI  - Risk factors for weight gain: a longitudinal study in non-weight loss treatment
      seeking overweight adults.
AB  - PURPOSE: To study some psycho-social variables in a sample of non-weight loss
      treatment-seeking overweight adults and to evaluate the weight outcome and the
      possible risk factors for weight gain over a 1-year period. METHODS: 167
      Overweight (BMI range 25-29.9) subjects (66 % females, age 50 +/- 10 years, BMI
      28 +/- 1.49) were recruited randomly in the surgeries of primary care physicians
      (PCPs). Data were collected through an ad hoc questionnaire with personal details
      and medical history. The following tests were administered: Binge Eating Scale
      (BES), Beck's Depression Inventory (BDI) and Body Uneasiness Test (BUT). Weight
      and height were measured using a mechanical balance with a stadiometer in
      standard conditions. At follow-up, 1 year after, updated data were collected for
      125 subjects (75 %). RESULTS: At follow-up, there was remarkable weight
      instability: only 16 % of the subjects maintained their baseline weight, 40.8 %
      showed a decrease, and 43.2 % gained weight. In 14.4 % of cases, weight gain led
      to obesity (BMI >=30). 18 individuals (14.4 %) reported having followed weight
      loss treatments in the last year, 11 among people with stable/decreased weight
      and 7 among those with weight gain. Lifetime comorbidity for anxiety and intense
      body uneasiness at baseline were the most important factors significantly
      associated with weight gain. Living with someone and habitually practicing sport
      resulted to play a protective role against weight increase. CONCLUSIONS: Our
      study highlights the importance of a multidimensional assessment (medical and
      psycho-social) of overweight patients, aimed to identify individuals at greater
      risk of weight gain. They should receive targeted interventions.

PMID- 25604247
TI  - Hypocalcemia, parathyroid hormone and calcitonin levels - association in
      critically ill children.

PMID- 25604246
TI  - Cardiac Arrest in Children: Relation to Resuscitation and Outcome.
AB  - OBJECTIVE: To determine the outcome of cardiac arrest in pediatric intensive care
      unit in relation to event variables. METHODS: The study included children with
      cardiac arrest who required resuscitation in pediatric intensive care unit over 1
      y period. Two outcome variables were measured. The first was success [return of
      spontaneous circulation (ROSC)] and the second was survival to discharge from
      pediatric intensive care unit. RESULTS: Out of 700 admissions, 172 (24.6 %)
      patients developed cardiac arrest that required resuscitation. Return of
      spontaneous circulation was achieved in 78 cases (45.3 %), 25 patients (14.5 %)
      survived to discharge and 94 patients (54.7 %) did not respond to resuscitations.
      Success and survival rates were significantly higher in cases resuscitated for <=
      20 min than in cases resuscitated for > 20 min (100 % and 33.3 % vs. 32.4 % and
      10.1 % respectively). Success and survival rates were better in patients
      undergoing mechanical ventilation than those not (48.1 % and 17.8 % vs. 37.2 %
      and 4.7 % respectively). Defibrillation was successful in 10 cases (25 %) and
      survival was in 1 case (0.5 %) and out of survivors, 80 % had good neurological
      outcome. CONCLUSIONS: The frequency of inhospital cardiac arrest was 24.6 % where
      45.3 % of them achieved successful resuscitation. The duration of cardiopulmonary
      resuscitation (<20 min) and mechanical ventilation were an indicator for better
      success and survival rates.

PMID- 25604248
TI  - Evaluation of a telephone advice system for remote intravenous thrombolysis in
      ischemic stroke: data from a United kingdom network.
AB  - BACKGROUND AND PURPOSE: There is limited evidence for remote stroke thrombolysis
      using telephone consultation and teleradiology. Results from a UK network using
      this treatment model are presented. METHODS: Retrospective study of consecutive
      patients thrombolysed in 5 hospitals, with well organized stroke services,
      between 2012 and 2013. Remote thrombolysis was compared with thrombolysis
      delivered in person for symptomatic intracerebral hemorrhage, death within 7
      days, and 90-day modified Rankin scores. RESULTS: Of 586 patients, 220 (37.5%)
      were thrombolysed remotely. The 2 groups were well matched (median age 77 years,
      NIHSS 12). Remote thrombolysis increased treatment time by 22 minutes. Outcomes
      were no different in the 2 groups (remote versus standard): symptomatic
      intracerebral hemorrhage (3.6% versus 4.6%), death within 7 days (6.4% versus
      7.1%), modified Rankin score <2 (46.0% versus 46.1%), and modified Rankin score 6
      (15% versus 17.5%) at 90 days. CONCLUSION: Telephone advice and teleradiology,
      within an organized system of care, can be an effective method of delivery of
      intravenous thrombolysis.

PMID- 25604249
TI  - MicroRNA-200c contributes to injury from transient focal cerebral ischemia by
      targeting Reelin.
AB  - BACKGROUND AND PURPOSE: MicroRNA (miR)-200c increases rapidly in the brain after
      transient cerebral ischemia but its role in poststroke brain injury is unclear.
      Reelin, a regulator of neuronal migration and synaptogenesis, is a predicted
      target of miR-200c. We hypothesized that miR-200c contributes to injury from
      transient cerebral ischemia by targeting reelin. METHODS: Brain infarct volume,
      neurological score and levels of miR-200c, reelin mRNA, and reelin protein were
      assessed in mice subjected to 1 hour of middle cerebral artery occlusion with or
      without intracerebroventricular infusion of miR-200c antagomir, mimic, or
      mismatch control. Direct targeting of reelin by miR-200c was assessed in vitro by
      dual luciferase assay and immunoblot. RESULTS: Pretreatment with miR-200c
      antagomir decreased post-middle cerebral artery occlusion brain levels of miR
      200c, resulting in a significant reduction in infarct volume and neurological
      deficit. Changes in brain levels of miR-200c inversely correlated with reelin
      protein expression. Direct targeting of the Reln 3' untranslated region by miR
      200c was verified with dual luciferase assay. Inhibition of miR-200c resulted in
      an increase in cell survival subsequent to in vitro oxidative injury. This effect
      was blocked by knockdown of reelin mRNA, whereas application of reelin protein
      afforded protection. CONCLUSIONS: These findings suggest that the poststroke
      increase in miR-200c contributes to brain cell death by inhibiting reelin
      expression, and that reducing poststroke miR-200c is a potential target to
      mitigate stroke-induced brain injury.

PMID- 25604250
TI  - To treat or not to treat? Pilot survey for minor and rapidly improving stroke.
AB  - BACKGROUND AND PURPOSE: Minor strokes and rapidly improving stroke symptoms are
      frequent exclusions for intravenous tissue-type plasminogen activator. We
      explored factors influencing tissue-type plasminogen activator treatment decision
      for minor strokes/rapidly improving stroke symptoms. METHODS: A pilot survey,
      including 110 case scenarios, was completed by 17 clinicians from 2 academic
      medical centers. Respondents were asked whether they would treat each case with
      tissue-type plasminogen activator at 60 minutes after emergency department
      admission. Cases varied by (1) National Institutes of Health Stroke Scale score
      at treatment decision time, (2) symptom pattern over time (improvement or
      worsening and then improving), (3) type of neurological deficit (3 main domains:
      motor, visual/sensory/ataxia, and language/neglect), and (4) age/occupation (4
      profiles). Logistic regression was used to predict probability of omission (pO).
      A binomial regression model was used to predict probability of treatment
      decision. RESULTS: Predicted probability of treatment decision was affected by
      National Institutes of Health Stroke Scale score (P<0.001) and age/occupation
      profiles (P<0.001) but not by symptom patterns (P=0.334). There were significant,
      albeit modest, main effects on probability of treatment decision for neurological
      domains. Responses were most likely omitted (P=0.027) for cases improvement
      pattern and language/neglect domain (pO=0.74; 95% confidence interval, 0.52-0.89)
      and with visual/sensory/ataxia domain (pO=0.74; confidence interval, 0.37-0.93)
      when compared with improvement pattern and motor domain (pO=0.17; confidence
      interval, 0.06-0.42) and to any worsening and then improving patterns
      (0.37<pO<0.56). CONCLUSIONS: This pilot survey provides the first quantitative
      evidence that National Institutes of Health Stroke Scale score is not the only
      determinant of treatment decision. A National Institutes of Health Stroke Scale
      score of 2 is the potential equipoise point, with the least consensus on
      treatment decision. These preliminary findings require validation in larger
      population surveys.

PMID- 25604251
TI  - Cysteine-sparing CADASIL mutations in NOTCH3 show proaggregatory properties in
      vitro.
AB  - BACKGROUND AND PURPOSE: Mutations in NOTCH3 cause cerebral autosomal-dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the
      most common monogenic cause of stroke and vascular dementia. Misfolding and
      aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are
      considered to be the key disease mechanisms. However, the significance of
      cysteine-sparing mutations is still debated. METHODS: We studied a family with
      inherited small vessel disease by standardized medical history, clinical
      examination, MRI, ultrastructural analysis of skin biopsies, and Sanger
      sequencing of all NOTCH3 exons. In addition, we performed in vitro
      characterization of NOTCH3 variants using recombinant protein fragments and a
      single-particle aggregation assay. RESULTS: We identified a novel cysteine
      sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy
      sibling. All mutation carriers exhibited a CADASIL typical brain imaging and
      clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro
      aggregation behavior of the D80G mutant was similar compared with cysteine
      affecting mutations. This was reproduced with cysteine-sparing mutations from
      previously reported families having a phenotype consistent with CADASIL.
      CONCLUSIONS: Our findings support the view that cysteine-sparing mutations, such
      as D80G, might cause CADASIL with a phenotype largely indistinguishable from
      cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3
      mutations offers novel insights into pathomechanisms and might represent a tool
      for estimating their clinical significance.

PMID- 25604252
TI  - Characterization of uncertainty in estimation of methane collection from select
      U.S. landfills.
AB  - Methane is a potent greenhouse gas generated from the anaerobic decomposition of
      waste in landfills. If captured, methane can be beneficially used to generate
      electricity. To inventory emissions and assist the landfill industry with energy
      recovery projects, the U.S. EPA developed the Landfill Gas Emissions Model
      (LandGEM) that includes two key parameters: the first-order decay rate (k) and
      methane production potential (L0). By using data from 11 U.S. landfills, Monte
      Carlo simulations were performed to quantify the effect of uncertainty in gas
      collection efficiency and municipal solid waste fraction on optimal k values and
      collectable methane. A dual-phase model and associated parameters were also
      developed to evaluate its performance relative to a single-phase model (SPM)
      similar to LandGEM. The SPM is shown to give lower error in estimating methane
      collection, with site-specific best-fit k values. Most of the optimal k values
      are notably greater than the U.S. EPA's default of 0.04 yr(-1), which implies
      that the gas generation decreases more rapidly than predicted at the current
      default. We translated the uncertainty in collectable methane into uncertainty in
      engine requirements and potential economic losses to demonstrate the practical
      significance to landfill operators. The results indicate that landfill operators
      could overpay for engine capacity by $30,000-780,000 based on overestimates of
      collectable methane.

PMID- 25604254
TI  - Thymosin beta4 attenuates microcirculatory and hemodynamic destabilization in
      sepsis.
AB  - OBJECTIVE: The actin polymerization regulator Thymosin beta4 (Tbeta4) has been
      shown to be involved in angiogenesis, wound healing, cell survival and anti
      inflammatory responses. We have previously shown that Tbeta4 is capable of
      recruiting pericytes, thus stabilizing the endothelial barrier function. Here, we
      analyzed whether treatment with Tbeta4 is able to reduce the pericytes loss in
      lipopolysaccharides (LPS)-induced sepsis and to improve the hemodynamic function
      and survival in C57BL/6 mice. METHODS: Fourteen days before LPS injection, the
      mice were injected with an adeno-associated virus carrying the Tbeta4
      (rAAV.Tbeta4) or LacZ gene (rAAV.LacZ). A sepsis-severity score was assessed, and
      non-invasive hemodynamic and permeability measurements were performed. Heart and
      muscle samples were analyzed for PECAM-1(+) capillaries and NG2(+)pericytes.
      RESULTS: At 36 h, there was a decrease of sepsis severity score in rAAV.Tbeta4
      treated animals as compared to rAAV.LacZ-treated control. rAAV.Tbeta4-treated
      animals displayed lower perivascular leakage and higher blood pressure compared
      to control. Of note, the rAAV.Tbeta4 group showed a higher pericyte count in
      heart and peripheral muscle samples. Finally, Tbeta4-treatment reduced mortality
      compared to control. CONCLUSION: The data indicate a preventive role of Tbeta4 in
      septic hypercirculation and highlight Tbeta4 as a potential therapeutic target in
      severe sepsis.

PMID- 25604253
TI  - The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular
      dystrophy mutations.
AB  - Analyzing the type and frequency of patient-specific mutations that give rise to
      Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic
      scientific research, trial planning, and improved clinical care. Locus-specific
      databases allow for the collection, organization, storage, and analysis of
      genetic variants of disease. Here, we describe the development and analysis of
      the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic
      data for 7,149 DMD mutations held within the database. A total of 5,682 large
      mutations were observed (80% of total mutations), of which 4,894 (86%) were
      deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger).
      There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of
      which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%)
      affected the splice sites. Point mutations totalled 756 (52% of small mutations)
      with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22
      (0.3%) mid-intronic mutations were observed. In addition, mutations were
      identified within the database that would potentially benefit from novel genetic
      therapies for DMD including stop codon read-through therapies (10% of total
      mutations) and exon skipping therapy (80% of deletions and 55% of total
      mutations). 

PMID- 25604255
TI  - Compression induces Ephrin-A2 in PDL fibroblasts via c-fos.
AB  - Ephrin-A2-EphA2 and ephrin-B2-EphB4 interactions have been implicated in the
      regulation of bone remodeling. We previously demonstrated a potential role for
      members of the Eph-ephrin family of receptor tyrosine kinases for bone remodeling
      during orthodontic tooth movement: compression-dependent upregulation of ephrin
      A2 in fibroblasts of the periodontal ligament (PDL) attenuated osteogenesis in
      osteoblasts of the alveolar bone. However, factors affecting the regulation of
      ephrin-A2 expression upon the application of compressive forces remained unclear.
      Here, we report a mechano-dependent pathway of ephrin-A2 induction in PDL
      fibroblasts (PDLFs) involving extracellular signal-regulated kinases (ERK) 1/2
      and c-fos. PDLF subjected to compressive forces (30.3 g/cm(2)) upregulated c-fos
      and ephrin-A2 mRNA and protein expression and displayed increased ERK1/2
      phosphorylation. Inhibition of the MAP kinase kinase (MEK)/ERK1/2 pathway using
      the specific MEK inhibitor U0126 significantly reduced ephrin-A2 messenger RNA
      upregulation upon compression. Silencing of c-fos using a small interfering RNA
      approach led to a significant inhibition of ephrin-A2 induction upon the
      application of compressive forces. Interestingly, ephrin-A2 stimulation of PDLF
      induced c-fos expression and led also to the induction of ephrin-A2 expression.
      Using a reporter gene construct in murine 3T3 cells, we found that ephrin-A2 was
      able to stimulate serum response element (SRE)-dependent luciferase activity. As
      the regulation of c-fos is SRE dependent, ephrin-A2 might induce c-fos via SRE
      activation. Taken together, we provide evidence for an ERK1/2- and c-fos
      dependent regulation of ephrin-A2 in compressed PDLF and suggest a novel pathway
      for ephrin-A2 induction emanating from ephrin-A2 itself. We showed previously
      that ephrin-A2 at compression sites might contribute to tooth movement by
      inhibiting osteogenic differentiation. The regulatory pathway of ephrin-A2
      induction during tooth movement identified in this study might be accessible for
      pharmacological interventions. 

PMID- 25604256
TI  - The efficacy of screening for common dental diseases by hygiene-therapists: a
      diagnostic test accuracy study.
AB  - Regularly attending adult patients are increasingly asymptomatic and not in need
      of treatment when attending for their routine dental examinations. As oral health
      improves further, using the general dental practitioner to undertake the
      "checkup" on regular "low-risk" patients represents a substantial and potentially
      unnecessary cost for state-funded systems. Given recent regulatory changes in the
      United Kingdom, it is now theoretically possible to delegate a range of tasks to
      hygiene-therapists. This has the potential to release the general dental
      practitioner's time and increase the capacity to care. The aim of this study is
      to compare the diagnostic test accuracy of hygiene-therapists when screening for
      dental caries and periodontal disease in regularly attending asymptomatic adults
      who attend for their checkup. A visual screen by hygiene-therapists acted as the
      index test, and the general dental practitioner acted as the reference standard.
      Consenting asymptomatic adult patients, who were regularly attending patients at
      10 practices across the Northwest of England, entered the study. Both sets of
      clinicians made an assessment of dental caries and periodontal disease. The
      primary outcomes measured were the sensitivity and specificity values for dental
      caries and periodontal disease. In total, 1899 patients were screened. The
      summary point for sensitivity of dental care professionals when screening for
      caries and periodontal disease was 0.81 (95% CI, 0.74 to 0.87) and 0.89 (0.86 to
      0.92), respectively. The summary point for specificity of dental care
      professionals when screening for caries and periodontal disease was 0.87 (0.78 to
      0.92) and 0.75 (0.66 to 0.82), respectively. The results suggest that hygiene
      therapists could be used to screen for dental caries and periodontal disease.
      This has important ramifications for service design in public-funded health
      systems. 

PMID- 25604257
TI  - Life expectancy and expected years of life lost to oral cancer in Taiwan: a
      nation-wide analysis of 22,024 cases followed for 10 years.
AB  - OBJECTIVES: This analysis examined the life expectancies (LE) and expected years
      of life lost (EYLL) in relation to oral cancer in Taiwan. MATERIALS AND METHODS:
      A semi-parametric extrapolation method was applied to estimate gender, age,
      histology, subsite, and stage stratified LE, EYLL of 22,024 pathologically
      verified oral cancer patients retrospectively recruited from the National Cancer
      Registry of Taiwan during 2002-2009, who were followed up to 2011. RESULTS: The
      patients were predominantly male 20,101, (91.3%), and over 80% were less than
      65years old. The mean age at diagnosis of males was younger than that of females
      (52.73years vs. 60.76years). The LE after diagnosis was longer among females than
      males (15.26years vs. 12.73years), with a smaller loss of the corresponding EYLL
      (8.88years vs. 14.05years), which prevails after stratification by age and stage.
      More than half of the oral cancer cases were diagnosed at a later stage, with
      2921 cases (13.3%) of stage III and 8488 (38.5%) of stage IV. The five-year
      overall survival rate of oral cancer for stages I, II, III, and IV were 78.98%,
      69.38%, 54.62%, and 36.17%, respectively. The earlier the diagnosis, the longer
      the life expectancy and the smaller the EYLL. CONCLUSIONS: We concluded that
      early detection and early intervention of oral cancer can prolong life expectancy
      and reduce the years of life lost, indicating the importance of proactive
      screening and oral hygiene.

PMID- 25604259
TI  - Factors influencing successful peer-reviewed publication of original research
      presentations from the American Society of Pediatric Otolaryngology (ASPO).
AB  - OBJECTIVE: To analyze factors associated with progression of an original
      scientific presentation at the American Society of Pediatric Otolaryngology
      (ASPO) Annual Meeting to publication in a peer-reviewed journal. A dataset of
      presenters was created to enable prospective follow-up to assess early
      impressions regarding publication success with longer-term publication outcomes.
      METHODS: Prior to the Annual ASPO meeting in 2013, a survey consisting of 10
      questions was e-mailed to all 59 presenters. Questions were designed to assess
      presenter expectations on publication, barriers to publishing, and experience in
      presenting, publishing and clinical practice. A second survey was sent 12 months
      later to those respondents of the first survey who were amenable to follow-up.
      RESULTS: Overall, 46 of 59 (78%) presenters responded to the initial survey prior
      to their ASPO 2013 presentation. Of these, 34 agreed to participate in a longer
      term follow-up of their presentation to publication experience. Of these 34,
      there were 17 who participated in the follow-up survey 1 year later. Just under
      half of the original respondents were residents (46%). All presenters (100%)
      planned to re-submit a revised manuscript if initially rejected. However, 35% of
      follow-up respondents did not make initial submission to a peer-reviewed journal.
      Results of a descriptive analysis suggest that more experienced researchers
      expect their submitted manuscript to be accepted for publication within a shorter
      time frame than those that have published fewer papers. Time was ranked as the
      greatest barrier to publication (60%) of those surveyed both in the initial
      prospective survey and for those who did not publish a paper in the follow-up
      survey (83%). CONCLUSION: This study suggests a strong desire and expectation of
      publishing ASPO presentations. Despite this expectation, past research and this
      data set suggest this expectation often does not materialize. "Time constraints"
      were the most commonly identified barrier to publication. To enhance
      dissemination of new findings from ASPO meetings, institutions and individuals
      should examine methods that facilitate and incentivize publication of findings in
      peer-reviewed publications.

PMID- 25604258
TI  - Tonsillectomy versus tonsillotomy: a study of parental preference.
AB  - OBJECTIVE: To directly sample the preference of representative parents who would
      be hypothetically considering tonsillotomy versus tonsillectomy for their child
      and assess the role of parental age, educational level, and risk aversion in
      making this choice. METHODS: Parents in a pediatric otolaryngology waiting room
      were asked to complete an anonymous survey which presented hypothetical scenarios
      for their child and described the specifics of tonsillectomy and tonsillotomy in
      terms of post-operative recovery, tonsil regrowth rates, and future strep throat
      risk. Other questions gathered parental demographic data and assessed risk
      tolerance. RESULTS: Two hundred and thirty-four parents completed the survey. A
      large majority of parents (201 of 234, 85.9%) preferred tonsillectomy over
      tonsillotomy for their child. Parental education and age were not associated with
      procedural preference. An increasing self-reported risk aversion score (p=0.003,
      Fisher's exact test) and a classification as risk averse using validated
      questions (p=0.034) were both associated with a preference for tonsillectomy over
      tonsillotomy. CONCLUSION: Parents of pediatric Otolaryngology patients strongly
      prefer tonsillectomy over tonsillotomy when described in general terms. This
      parental choice appears to correlate with risk aversion of the possible long-term
      complications of tonsillotomy including the need for future treatment of
      streptococcal pharyngitis and/or regrowth of the tonsils and subsequent revision
      tonsil surgery.

PMID- 25604260
TI  - Subjective and objective assessments of seasonal effect in children with seasonal
      allergic rhinitis.
AB  - BACKGROUND: Epidemiological and clinical studies suggest a relationship between
      rhinitis and asthma. Upper and lower airways may be influenced by a common
      inflammatory process. OBJECTIVE: This study aimed to investigate the
      relationships between rhinitis symptom scores, and both nasal and bronchial
      airflow among children with seasonal allergic rhinitis (SAR) by means of
      spirometric and rhinomanometric measurement during and outside the pollen season.
      METHODS: Twenty-nine children with both seasonal allergic rhinitis and asthma
      (AR+A), 30 children with SAR and no asthma (AR) and 36 non-allergic healthy
      children were evaluated prospectively during and outside the pollen season.
      Symptom severity was evaluated using both total symptom score and visual analog
      score (VAS). All participants also received rhinomanometric evaluation and
      pulmonary function testing. RESULTS: In children with SAR the median total nasal
      flow, FEV1, FEF25-75 values were lower than control group during pollen season
      (p=0.01, p<0.001 and p<0.001 respectively). They had also higher total nasal
      resistance compared with control groups (p=0.01). Nasal symptom scores were
      higher among patients with concurrent asthma than patients who had only SAR out
      of pollen season (p<0.001). There was no significant difference between SAR
      participants with or without asthma and control group in terms of total nasal
      flow and total nasal resistance measured out of season (p=0.105 and p=0.19).
      FEF25-75 values of patients with and without asthma were significantly lower than
      those of controls out of season (p=0.022, p<0.001 respectively). CONCLUSION: Our
      data suggests that as the presence of AR worsens asthma control, the presence of
      asthma may worsen symptoms of AR out of pollen season. We found that total nasal
      flow, FEV1, FEF25-75 values of patients with SAR were lower than those of
      controls out of season. FEF25-75 values of patients with asthma and without
      asthma were significantly lower than those of controls out of season. Thus, a
      careful evaluation of lower airways should be performed in even patients with
      seasonal allergic rhinitis alone.

PMID- 25604261
TI  - Non-cleft causes of velopharyngeal dysfunction: implications for treatment.
AB  - Although a history of cleft palate is the most common cause of velopharyngeal
      dysfunction (VPD), there are other disorders that can also cause hypernasality
      and/or nasal emission. These include other structural anomalies of the
      velopharyngeal valve (velopharyngeal insufficiency), neurophysiological disorders
      that result in inadequate velopharyngeal movement (velopharyngeal incompetence),
      and even faulty articulation placement in the pharynx (velopharyngeal
      mislearning). Unfortunately, individuals with non-cleft causes of hypernasality
      and/or nasal emission do not typically present at a cleft palate/craniofacial
      center where there are professionals who specialize in the evaluation and
      treatment of these disorders. As a result, they are often misdiagnosed and do not
      receive appropriate treatment. In this review, we present various conditions that
      can cause hypernasality and/or nasal emission during speech. We discuss
      appropriate treatment based on the underlying cause of the condition. It is
      important that pediatric otolaryngologists are able to recognize these disorders
      so that affected patients are referred to specialists in velopharyngeal
      dysfunction for treatment. 

PMID- 25604262
TI  - Twisted baskets.
AB  - A preparative procedure for obtaining a pair of twisted molecular baskets, each
      comprising a chiral framework with either right ((P)-1syn) or left ((M)-1syn)
      sense of twist and six ester groups at the rim has been developed and optimized.
      The racemic (P/M)-1syn can be obtained in three synthetic steps from accessible
      starting materials. The resolution of (P/M)-1syn is accomplished by its
      transesterification with (1R,2S,5R)-(-)-menthol in the presence of a Ti(IV)
      catalyst to give diastereomeric 8(P) and 8(M). It was found that dendritic-like
      cavitands 8(P) and 8(M), in CD2Cl2, undergo self-inclusion ((1)H NMR
      spectroscopy) with a menthol moiety occupying the cavity of each host.
      Importantly, the degree of inclusion of the menthol group was ((1)H NMR
      spectroscopy) found to be greater in the case of 8(P) than 8(M). Accordingly, it
      is suggested that different folding characteristic of 8(P) and 8(M) ought to
      affect the physicochemical characteristics of the hosts to permit their effective
      separation by column chromatography. The absolute configuration of 8(P)/8(M),
      encompassing right- and left-handed "cups", was determined with the exciton
      chirality method and also verified in silico (DFT: B3LYP/TZVP). Finally, the
      twisted baskets are strongly fluorescent due to three naphthalene chromophores,
      having a high fluorescence quantum yield within the rigid framework of 8(P)/8(M).

PMID- 25604263
TI  - Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae.
AB  - Acyclovir is a commonly-used drug for treating herpes simplex virus (HSV)
      infections, but with its wide clinical application, more and more resistant
      strains have been found. Therefore, seeking a drug that can act against acyclovir
      resistant virus has become an important goal of drug screening and development.
      In this study, plaque reduction assay, real-time PCR, Western blot, and
      immunofluorescence technique were used to investigate the antiviral effect of
      Eucheuma gelatinae polysaccharide (EGP) on HSV and to preliminarily clarify the
      in vitro anti-HSV mechanism of EGP. EGP was found to significantly inhibit HSV
      infection in vitro and displayed a good inhibitory effect on acyclovir-resistant
      strains. More detailed experiments have shown that EGP prevented early HSV-1
      infection through directly inactivating HSV-1 particles and impairing virus
      attachment, but without effect on viral penetration. EGP also inhibited the RNA
      synthesis of HSV-1 early gene and late gene as well as viral DNA replication; no
      effect on immediate-early gene synthesis was observed. Besides, through
      immunofluorescence and western blot, we found that EGP significantly affected the
      protein synthesis of HSV-1. Taken together, these results demonstrate that EGP
      exerts its anti-HSV activity mainly through impeding early HSV-1 infection and
      inhibiting viral RNA and DNA syntheses. The weak cytotoxicity, strong viral
      inactivation as well as attachment inhibition activity enable EGP to be a
      virucide candidate for HSV therapy, especially for drug-resistant strains.

PMID- 25604266
TI  - First insights into the microbial diversity in the omasum and reticulum of bovine
      using Illumina sequencing.
AB  - The digestive systems of mammals harbor a complex gut microbiome, comprising
      bacteria and other microorganisms that confer metabolic and immunological
      benefits to the host. Ruminants that digest plant-based foods have a four
      compartment stomach consisting of the rumen, reticulum, omasum, and abomasum. The
      microorganisms in the stomach are essential for providing the host with critical
      nutrients. However, the majority of these microorganisms are unknown species. The
      microbiome of the stomach is diverse, and the majority of these organisms cannot
      be cultured. Next-generation sequencing (NGS) combined with bioinformatic
      analysis tools have allowed the dissection of the composition of the microbiome
      in samples collected from a specific environment. In this study, for the first
      time, the bacterial composition in two compartments, the reticulum and the
      omasum, of bovine were analyzed using a metagenomic approach and compared to the
      bacterial composition of the rumen. These data will assist in understanding the
      biology of ruminants and benefit the agricultural industry. The diversity and
      composition of the bacterial community in samples collected from the rumen,
      reticulum, and omasum of bovines in the Changchun Region of Northeast China were
      analyzed by sequencing the V3 region of the 16S rRNA gene using a barcoded
      Illumina paired-end sequencing technique, and the primary composition of the
      microbiome in the rumen, reticulum, and omasum of the bovines was determined.
      These microbiomes contained 17 phyla and 107 genera in all three samples. Five
      phyla, Bacteroidetes, Firmicutes, Proteobacteria, Spirochaetes, and
      Lentisphaerae, were the most abundant taxonomic groups. Additionally, the
      different stomach compartments harbored different compositions of the
      microorganisms. 

PMID- 25604265
TI  - Analysis of microbial community composition in a lab-scale membrane distillation
      bioreactor.
AB  - AIMS: Membrane distillation bioreactors (MDBR) have potential for industrial
      applications where wastewater is hot or waste heat is available, but the role of
      micro-organisms in MDBRs has never been determined, and thus was the purpose of
      this study. METHODS AND RESULTS: Microbial communities were characterized by
      bacterial and archaeal 16S and eukaryotic 18S rRNA gene tag-encoded
      pyrosequencing of DNA obtained from sludge. Taxonomy-independent analysis
      revealed that bacterial communities had a relatively low richness and diversity,
      and community composition strongly correlated with conductivity, total nitrogen
      and bound extracellular polymeric substances (EPS). Taxonomy-dependent analysis
      revealed that Rubrobacter and Caldalkalibacillus were abundant members of the
      bacterial community, but no archaea were detected. Eukaryotic communities had a
      relatively high richness and diversity, and both changes in community composition
      and abundance of the dominant genus, Candida, correlated with bound EPS.
      CONCLUSIONS: Thermophilic MDBR communities were comprised of a low diversity
      bacterial community and a highly diverse eukaryotic community with no archea
      detected. Communities exhibited low resilience to changes in operational
      parameters. Specifically, retenatate nutrient composition and concentration was
      strongly correlated with the dominant species. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides an understanding of microbial community diversity in
      an MDBR, which is fundamental to the optimization of reactor performance.

PMID- 25604264
TI  - Cancer stem cells: targeting the roots of cancer, seeds of metastasis, and
      sources of therapy resistance.
AB  - With the goal to remove the roots of cancer, eliminate metastatic seeds, and
      overcome therapy resistance, the 2014 inaugural International Cancer Stem Cell
      (CSC) Conference at Cleveland, OH, convened together over 320 investigators,
      including 55 invited world-class speakers, 25 short oral presenters, and 100
      poster presenters, to gain an in-depth understanding of CSCs and explore
      therapeutic opportunities targeting CSCs. The meeting enabled intriguing
      discussions on several topics including: genetics and epigenetics; cancer origin
      and evolution; microenvironment and exosomes; metabolism and inflammation;
      metastasis and therapy resistance; single cell and heterogeneity; plasticity and
      reprogramming; as well as other new concepts. Reports of clinical trials
      targeting CSCs emphasized the urgent need for strategically designing
      combinational CSC-targeting therapies against cancer.

PMID- 25604267
TI  - Anagrelide platelet-lowering effect is due to inhibition of both megakaryocyte
      maturation and proplatelet formation: insight into potential mechanisms.
AB  - BACKGROUND AND OBJECTIVES: Anagrelide represents a treatment option for essential
      thrombocythemia patients. It lowers platelet counts through inhibition of
      megakaryocyte maturation and polyploidization, although the basis for this effect
      remains unclear. Based on its rapid onset of action, we assessed whether, besides
      blocking megakaryopoiesis, anagrelide represses proplatelet formation (PPF) and
      aimed to clarify the underlying mechanisms. METHODS AND RESULTS: Exposure of cord
      blood-derived megakaryocytes to anagrelide during late stages of culture led to a
      dose- and time-dependent inhibition of PPF and reduced proplatelet complexity,
      which were independent of the anagrelide-induced effect on megakaryocyte
      maturation. Whereas anagrelide was shown to phosphorylate cAMP-substrate VASP,
      two pharmacologic inhibitors of the cAMP pathway were completely unable to revert
      anagrelide-induced repression in megakaryopoiesis and PPF, suggesting these
      effects are unrelated to its ability to inhibit phosphodiesterase (PDE) 3. The
      reduction in thrombopoiesis was not the result of down-regulation of
      transcription factors which coordinate PPF, while the myosin pathway was
      identified as a candidate target, as anagrelide was shown to phosphorylate the
      myosin light chain and the PPF phenotype was partially rescued after inhibition
      of myosin activity with blebbistatin. CONCLUSIONS: The platelet-lowering effect
      of anagrelide results from impaired megakaryocyte maturation and reduced PPF,
      both of which are deregulated in essential thrombocythemia. These effects seem
      unrelated to PDE3 inhibition, which is responsible for anagrelide's
      cardiovascular side-effects and antiplatelet activity. Further work in this field
      may lead to the potential development of drugs to treat thrombocytosis in
      myeloproliferative disorders with an improved pharmacologic profile.

PMID- 25604268
TI  - Repetitive injection method: a tool for investigation of injection zone formation
      and its compression in microfluidic liquid chromatography.
AB  - Sample introduction in microfluidic liquid chromatography often generates wide
      zones rather than peaks, especially when a large sample volume (relative to
      column volume) is injected. Formation of wide injection zones can be further
      amplified when the sample is dissolved in a strong eluent. In some cases sample
      breakthrough may occur, especially when the injection is performed into short
      trapping columns. To investigate the band formation and subsequent zone focusing
      under gradient elution in situations such as these, we developed the Repetitive
      Injection Method (RIM), based on the temporally resolved introduction of two
      discrete peaks to a column, mimicking both the leading and trailing edges of a
      larger, singly injected sample zone. Using titanium microfluidic 0.32 mm I.D.
      columns, the results of RIM experiments were practically identical to injection
      of a correspondingly larger single zone volume. It was also experimentally shown
      that zone width (spacing between two injected peaks) decreases during gradient
      elution. We utilized RIM experiments to investigate wide sample zones created by
      strong sample solvent, and subsequent gradient zone focusing for a series of
      compounds. This experimental work was compared with computationally simulated
      chromatograms. The success of sample focusing during injection and gradient
      elution depends not only on an analyte's absolute retention, but also on how
      rapidly the analyte's retention changes during the mobile phase gradient.

PMID- 25604269
TI  - Automated and portable solid phase extraction platform for immuno-detection of
      17beta-estradiol in water.
AB  - A fully automated and portable system for solid phase extraction (SPE) has been
      developed for the analysis of the natural hormone 17beta-estradiol (E2) in
      environmental water by enzyme linked immuno-sorbent assay (ELISA). The system has
      been validated with de-ionized and artificial sea water as model samples and
      allowed for pre-concentration of E2 at levels of 1, 10 and 100 ng/L with only 100
      ml of sample. Recoveries ranged from 24+/-3% to 107+/-6% depending on the
      concentration and sample matrix. The method successfully allowed us to determine
      the concentration of two seawater samples. A concentration of 15.1+/-0.3 ng/L of
      E2 was measured in a sample obtained from a food production process, and 8.8+/
      0.7 ng/L in a sample from the Adriatic Sea. The system would be suitable for
      continuous monitoring of water quality as it is user friendly, and as the method
      is reproducible and totally compatible with the analysis of water sample by
      simple immunoassays and other detection methods such as biosensors.

PMID- 25604270
TI  - Evaluation of column hardware on liquid chromatography-mass spectrometry of
      phosphorylated compounds.
AB  - The influences of column hardware, such as chromatographic tubes and frits, on
      liquid chromatography-mass spectrometry (LC-MS) analysis of phosphorylated
      compounds were evaluated. The signal to noise ratio (S/N) and the intensity of
      flavin adenine dinucleotide (FAD) using a glass lined tube and polyethylene frit
      (GL-PE) column was approximately 170 and 90 times higher, respectively, than
      those using conventional stainless steel tube and stainless steel frit (S-S)
      column. In addition, the retention time of FAD using GL-PE column was the
      shortest compared to other columns. Interaction between phosphorylated compounds
      and metal ions in the flow path in the S-S column was stronger than that between
      them and the GL-PE column. Thus, the metal ions in the flow path in GL-PE column
      were low. Since the specific surface area of a pair of frits was 70 times larger
      than that of a chromatographic tube (150 mm*2.1 mm), the frits were found to have
      more effective improvement of the S/N as well as the intensity than the
      chromatographic tubes, when phosphorylated compounds were analyzed by LC-MS. When
      the evaluated phosphorylated compounds were analyzed by LC-MS(/MS) using a GL-PE
      column, the intensity and S/N were increased.

PMID- 25604271
TI  - Editorial on "A review of microdialysis coupled to microchip electrophoresis for
      monitoring biological events" by Rachel A. Saylor and Susan M. Lunte.

PMID- 25604272
TI  - The many faces of packed column supercritical fluid chromatography--a critical
      review.
AB  - Packed column sub- and supercritical fluid chromatography (SFC) is a versatile
      separation method: on the one hand the number of parameters acting on the quality
      of a separation is very large, and the effects of these parameters can be complex
      (and not always fully understood). But on another hand, due to numerous
      advantageous properties of CO2-based mobile phases, method development is a fast
      task. This paper is a review of the main features of SFC, focusing essentially on
      achiral separations. However, several fundamental aspects discussed here are also
      relevant to chiral SFC separations. This is not intended to be an extensive
      review, as the way to practice SFC has somewhat evolved with time. We rather
      wished to provide an expert opinion on the characteristics of the method,
      pointing at the sources of difficulty and displaying the wide possibilities that
      it offers. A large number of selected applications concerning several different
      areas are also presented. 

PMID- 25604273
TI  - Growth of metal-organic framework HKUST-1 in capillary using liquid-phase epitaxy
      for open-tubular capillary electrochromatography and capillary liquid
      chromatography.
AB  - Much attention is being paid to applying metal-organic frameworks (MOFs) as
      stationary phases in chromatography because of their fascinating properties, such
      as large surface-to-volume ratios, high levels of porosity, and selective
      adsorption. HKUST-1 is one of the best-studied face-centered-cubic MOF containing
      nano-sized channels and side pockets for film growth. However, growth of HKUST-1
      framework inside capillary column as stationary phase for capillary
      electrochromatography is a challenge work. In this work, we carry out the growth
      of HKUST-1 on the inner wall of capillary by using liquid-phase epitaxy process
      at room temperature. The fabricated HKUST-1@capillary can be successfully used
      for the separation of substituted benzene including methylbenzene, ethylbenzene,
      styrene, chlorobenzene, bromobenzene, o-dichlorobenzene, benzene series, phenolic
      acids, and benzoic acids derivates. High column efficiency of 1.5*10(5) N/m for
      methylbenzene was achieved. The formation of HKUST-1 grown in the capillary was
      confirmed and characterized by scanning electron microscopy images, Fourier
      transform infrared spectra and X-ray diffraction. The column showed long lifetime
      and excellent stability. The relative standard deviations for intra-day and inter
      day repeatability of the HKUST-1@capillary were lower than 7%.

PMID- 25604274
TI  - Trigeminal neuralgia due to neurovascular conflicts from venous origin: an
      anatomical-surgical study (consecutive series of 124 operated cases).
AB  - BACKGROUND: Veins as the source of trigeminal neuralgias (TN) lead to
      controversies. Only a few studies have specifically dealt with venous implication
      in neurovascular conflicts (NVC). The aim of this study was the anatomical
      surgical description of the compressive veins found during micro-vascular
      decompression (MVD). METHODS: Patients retained were those in whom a vein was
      considered compressive, alone, or in association with an artery. The study
      defined the type of vein involved, its situation along, the location around the
      root, and management. For this study, denomination of veins in relation with the
      root was revisited. RESULTS: Of the 326 consecutive patients who underwent MVD
      from 2005 to 2013, 124 (38.0 %) had a venous conflict, alone in 29 (8.9 %), or in
      association with an artery in 95 (29.1 %). The compressive veins belonged to one
      of the two venous systems described: the superficial or the deep superior
      petrosal venous system (sSPVS or dSPVS). A vein from sSPVS was found compressive
      in 81 cases (59.6 %), for the major part it was the pontine affluent of the
      superior petrosal vein (48 cases). The conflict was situated at TREZ in 28.4 %,
      mid-cisternal portion in 50.6 %, and porus in 8.6 %. The dSPVS was found
      compressive in 55 cases (40.4 %), almost always a transverse vein at porus (51
      cases). Decompression was coagulation-division of the conflicting vein in 36.8 %
      and simple cleavage in the other. CONCLUSIONS: The study shows the frequent
      implication of veins in NVC as the source of TN. NVC are not only at TREZ but
      also at mid-cisternal portion and porus of Meckel cave.

PMID- 25604275
TI  - Manipulating magnetism of MnO nano-clusters by tuning the stoichiometry and
      charge state.
AB  - In this paper, we have studied the composition dependent evolution of geometric
      and magnetic structures of MnO clusters within density functional theory. The
      magnetic structures are determined by the competition between direct and
      superexchange interactions, which have been analyzed by the parameters obtained
      from maximally localized Wannier functions. The intrinsic electronic structures
      of the clusters have been thoroughly studied by looking into the hybridization
      (quantified using the Hybridization Index) and charge transfer scenario. Further,
      the importance of electron correlation in describing simple Mn-dimer and MnO
      clusters has been discussed within the Hubbard model and hybrid exchange
      correlation functional. Our calculated vertical detachment energies of off
      stoichiometric MnO clusters compare well with the recent experimental results.
      Interestingly, the charged state of the cluster strongly influences the geometry
      and the magnetic structure of the cluster, which are very different from the
      corresponding neutral counterpart. We have demonstrated that the exchange
      interaction between Mn atoms can be switched between ferromagnetic and
      anitiferromagnetic ones by changing the charge state and hence can be useful for
      spin-based information technology. 

PMID- 25604276
TI  - Extensively drug-resistant Acinetobacter baumannii belonging to the international
      clonal lineage I in a Russian burn intensive care unit.
AB  - The high incidence of mortality in patients with severe burns can be attributed
      to bloodstream infections caused by drug-resistant microorganisms. Multilocus
      variable-number tandem repeat analysis (MLVA), multilocus sequence typing (MLST)
      and class 1 integron PCR amplification were performed to investigate an
      extensively drug-resistant Acinetobacter baumannii (XDR-AB) strain recovered from
      a blood culture of a patient admitted to a burn intensive care unit in St
      Petersburg (Russian Federation). This case study describes an XDR-AB strain of
      multilocus sequence type ST231 with a blaGES-12 gene cassette encoding a very
      potent ceftazidimase located inside of a composite class 1 integron. This is the
      first documented case of XDR-AB belonging to the international clonal lineage I
      in Russia. 

PMID- 25604277
TI  - Azithromycin and ciprofloxacin: a possible synergistic combination against
      Pseudomonas aeruginosa biofilm-associated urinary tract infections.
AB  - Biofilm formation is becoming a predominant feature in nosocomial infections.
      Since biofilms are increasingly resistant to antibiotics, making monotherapy
      ineffective, combination therapy appears to be relevant for their eradication.
      This study assessed the potential of azithromycin (AZM) and ciprofloxacin (CIP)
      alone and in combination in vitro and in a mouse model of urinary tract infection
      (UTI) induced with biofilm cells of Pseudomonas aeruginosa. In vitro
      antibacterial and antibiofilm activities of antibiotics alone and in combination
      were assessed using the fractional inhibitory concentration index (FICI), time
      kill analysis and confocal laser scanning microscopy (CLSM). In vivo efficacy was
      evaluated in a UTI model by quantitation of bacterial burden in kidney and
      bladder tissue, renal histopathology, pathology index factors (MDA and NO), and
      pro-inflammatory (MIP-2 and IL-6) and anti-inflammatory (IL-10) cytokines. MICs
      of AZM and CIP for strain PAO1 were 256 and 0.5 MUg/mL, respectively; MBECs were
      4096 and 1024 MUg/mL. Synergistic interaction was observed between AZM and CIP
      both against planktonic and biofilm bacteria (FICI<0.5). The combination was also
      able to inhibit biofilm formation (at MIC levels) as observed with CLSM. Oral
      therapy with AZM (500 mg/kg) and CIP (30 mg/kg) combination in mice for 4 days
      showed accelerated clearance of bacteria from kidney and bladder tissue, improved
      renal histopathology, decreased levels of MDA and NO, significant decline in MIP
      2 and IL-6, and increased IL-10 in the kidney (P<0.0001). We conclude that
      AZM+CIP therapy holds promise against biofilm-associated UTIs as it confers
      antibacterial, immunomodulatory and anti-inflammatory effects.

PMID- 25604278
TI  - Ag5IO6: novel antibiofilm activity of a silver compound with application to
      medical devices.
AB  - This work explores the unique antibiofilm activity of pentasilver hexaoxoiodate
      (Ag(5)IO(6)). To test this activity, wound dressings were impregnated with
      Ag(5)IO(6) and compared with various commercially available silver-containing
      dressings, as well as dressings containing chlorhexidine, iodine and
      polyhexamethylene biguanide (PHMB). The materials were tested against Pseudomonas
      aeruginosa, Staphylococcus aureus and Candida albicans for their ability to
      prevent micro-organism adherence, eliminate planktonic micro-organisms and
      disrupt/eliminate mature biofilms generated using the MBECTM assay within 24 h of
      microbial exposure. Only the Ag(5)IO(6)-containing dressings were able to prevent
      adherence and eliminate surrounding planktonic micro-organisms for all species
      tested for >=28 days of elution with log reductions >4. Two other silver
      dressings succeeded against P. aeruginosa only after 28 elution days, whilst the
      PHMB dressing succeeded after 28 days of elution against C. albicans only.
      Ag(5)IO(6)-containing dressings were able to generate >4 log reductions against
      all biofilms tested. The only commercial dressings able to generate >4 log
      reductions against biofilms were iodine against P. aeruginosa and S. aureus, and
      PHMB against S. aureus. The Ag(5)IO(6) dressings demonstrated complete kill (>4
      log reduction) in a standard 30-min planktonic log reduction assay against all
      species. These results demonstrate that Ag(5)IO(6) has superior activity to a
      number of antimicrobials, with broad-spectrum efficacy that includes long-term
      prevention of microbial adherence, rapid kill of planktonic micro-organisms, and
      the ability to disrupt and eliminate mature biofilms. Thus, Ag(5)IO(6) may be a
      valuable antimicrobial agent for use in a number of medical device applications,
      including wound dressings, various catheters or implants.

PMID- 25604279
TI  - [A pioneer cancer registry in Latin America].

PMID- 25604280
TI  - [Cancer in Mexico: recommendations for its control].

PMID- 25604281
TI  - [50 years of the Population-Based Cancer Registry of Cali, Colombia].

PMID- 25604282
TI  - [Monthly attendance at an immunodeficiency virus clinic acquired by resurtible
      prescription and adherence to antiretroviral treatment].

PMID- 25604283
TI  - [Mexican scientific production on influenza, 2000-2012].

PMID- 25604284
TI  - [Clarifications on observational studies and on the prevalence].

PMID- 25604285
TI  - Treating patients with severe preeclampsia and eclampsia in Oaxaca, Mexico.

PMID- 25604286
TI  - An education-support program that addresses many of the shortcomings of medical
      social service in Mexico.

PMID- 25604287
TI  - Cost analysis of different cervical cancer screening strategies in Mexico.
AB  - OBJECTIVE: To compare the costs and number of undetected cases of four cervical
      cancer screening strategies (CCSS) in Mexico. MATERIALS AND METHODS: We estimated
      the costs and outcomes of the following CCSS: a) conventional Papanicolaou smear
      (Pap) alone; b) high-risk human papilloma virus testing (HR-HPV) as primary
      screening with Pap as reflex triage; c) HR-HPV as primary screening with HPV
      16/18 typing, liquid-based cytology (LBC) and immunostaining for p16/Ki67 testing
      as reflex triage, and d) co-testing with HR-HPV and LBC with HPV-16/18 typing and
      immunostaining for p16/Ki67 as reflex triage. The outcome of interest was high
      grade cervical lesions or cervical cancer. RESULTS: HR-HPV testing, HPV typing,
      LBC testing and immunostaining is the best alternative because it is the least
      expensive option with an acceptable number of missed cases. CONCLUSIONS: The
      opportunity costs of a poor quality CCSS is many false negatives. Combining
      multiple tests may be a more cost-effective way to screen for cervical cancer in
      Mexico.

PMID- 25604288
TI  - [Response to the letter to the editor "An education-support program that
      addresses many of the shortcomings of medical social service in Mexico"].

PMID- 25604289
TI  - Epidemiology of cervical cancer in Colombia.
AB  - OBJECTIVE: To describe the incidence, mortality, time trends and prognostic
      factors for cervical cancer in Cali, Colombia, and to review the molecular
      epidemiological evidence showing that HPV is the major and necessary cause of
      cervical cancer and the implications of this discovery for primary and secondary
      prevention. MATERIALS AND METHODS: Incidence rates of cervical cancer during a 45
      year period (1962-2007) were estimated based on the population-based cancer
      registry of Cali and the mortality statistics from the Municipal Health
      Secretariat of Cali. Prognostic factors were estimated based on relative
      survival. Review of the molecular epidemiological evidence linking HPV to
      cervical cancer was focused on the studies carried out in Cali and in other
      countries. RESULTS: Incidence rates of squamous cell carcinoma (SCC) declined
      from 120.4 per 100 000 in 1962-1966 to 25.7 in 2003-2007 while those of
      adenocarcinoma increased from 4.2 to 5.8. Mortality rates for cervical cancer
      declined from 18.5 in 1984-1988 to 7.0 per 100 000 in 2009-2011. Survival was
      lower in women over 65 years of age and in clinical stages 3-4. Review of the
      molecular epidemiological evidence showed that certain types of HPV are the
      central and necessary cause of cervical cancer. CONCLUSIONS: A decline in the
      incidence and mortality of SCC and an increase in the incidence of adenocarcinoma
      during a 45-year period was documented in Cali, Colombia.

PMID- 25604290
TI  - [Prostate cancer in Cali, Colombia, 1962-2011: incidence, mortality and
      survival].
AB  - OBJECTIVE: To analyze the trend in prostate cancer survival, incidence and
      mortality rates in Cali, Colombia from 1962 to 2011. MATERIALS AND METHODS: Based
      on the Cancer Registry of Cali, Colombia and the mortality registry of the City's
      Public Health Secretary, incidence, mortality age-standardized rates and relative
      survival were calculated during 1962-2011. RESULTS: Prostate cancer incidence
      rates increased sharply between 1986 and 2002 (APC: 6.21%) and then leveled off.
      Mortality diminished in 1997 in men older than 70 years-old while in men aged 50
      69 years declined since 1981. The 5-year-relative-survival was 69.8% (CI95% 67.5
      72.0) and it was significantly associated with age, quinquennial period of
      diagnosis and socioeconomic strata. CONCLUSION: The increase in incidence rates
      of prostate cancer in time coincides with the implementation of the PSA in Cali.
      There is evidence of improvement in prostate cancer survival, and decreased
      prostate cancer mortality.

PMID- 25604291
TI  - Burden of breast cancer in Cali, Colombia: 1962-2012.
AB  - OBJECTIVE: To describe the behavior of breast cancer (BC)during the 1962-2012
      period from information provided by the Cali Cancer Registry and the Municipal
      Health Secretariat of Cali. MATERIALS AND METHODS: The incidence trend (1962
      2007) and mortality trend (1984-2012) for breast cancer was studied and relative
      survival (RS)(1995-2004) was estimated. Age-standardized incidence and mortality
      rates to the world population (ASIR(w)/ASMR(w)) were expressed per 100000 persons
      year. Their temporal trend was examined with the annual percent of change (APC),
      and the Cox model was used to analyze the variables that influenced the survival
      of women with breast cancer. RESULTS: The risk of breast cancer significantly
      increased in Cali through the 1962-2007 period, with an APC =1.7(95%CI:1.4-2.0).
      The ASIR(w) of BC increased from 27.1 in 1962 to 48.0 in 2007 and currently there
      are more than 500 cases reported annually. The mortality for BC has remained
      stable since 1984; in the 2009-2012 period, the ASMR(w) was 14.2. The 5-year RS
      was 69% (95%CI:66-71) from 2000-2004 and 62% (95%CI:59-65) from 1995-1999. The
      risk of death (HR) from BC was greater in persons from lower socioeconomic strata
      (SES) than from higher SES, HR=1.9(95%CI:1.3-2.9) and in those older than 70
      years vs. <50, HR=1.6(95%CI:1.1-2.2). CONCLUSION: Mortality remained stable while
      incidence increased and survival improved, which may be associated with better
      detection and advances in treatment.

PMID- 25604292
TI  - [Colorectal cancer incidence, mortality and survival in Cali, Colombia, 1962
      2012].
AB  - OBJECTIVE: To study the colorectal cancer (CRC) behavior in Cali, Colombia,
      during the 1963-2012 period using data from the Population-based Cancer Registry
      of Cali and the Municipal Health Secretariat of Cali. MATERIALS AND METHODS: An
      ecological time series analysis to study the CRC incidence (1962-2007) and
      mortality (1984-2012) rate trends; and a survival analysis of CRC cases
      registered in Cali between 1995 and 2004 were conducted. The age-standardized
      temporal trend of incidence (I-ASR) and mortality (M-ASR) rates were studied
      using an annual percent change (APC). The 5-year relative survival was estimated
      and a multivariate analysis was performed using the Cox proportional hazard
      regression model. RESULTS: During the 1962-2007 period, CRC TTIR increased in men
      and women living in Cali [APC= 2.6 (95% CI 2.2-3.0) and APC= 2.2% (95% CI 1.8
      2.7), respectively]. In the 1984-2012 period, the TTMR remained stable in women
      but increased in men in all age groups [APC= 1.8 (95% CI 0.8-2.8)]. The 5-year
      relative survival was independent of sex and increased from 29.7% in 1995-1999 to
      39.8% in 2000-2004. The risk of dying from CRC was higher in people of lower
      socio-economic status (SES) vs higher SES [HR= 2.1 (95% CI: 1.7-2.6)], among
      people older than 70 years of age vs younger than 50 years [HR= 2.4 (95% CI: 1.9
      2.9)], and for the 1995-1999 period vs 2000-2004 period [HR= 1.5 (95% CI 1.3
      1.7)]. CONCLUSION: CRC is beginning to take a prominent place among the most
      important cancers in Cali, Colombia.

PMID- 25604293
TI  - [Oral cancer in Cali, Colombia: a population-based analysis of incidence and
      mortality trends].
AB  - OBJECTIVE: To describe the time trends of the incidence and mortality rates of
      oral cancer (OC) in Cali, Colombia between 1962-2007. MATERIALS AND METHODS: Age
      standardized (Segi's world population) incidence (ASIR) and mortality (ASMR)
      rates for oral cancer were estimated using data from the Population-based Cancer
      Registry of Cali, Colombia and from the database of the Municipal Secretary of
      Public Health (MSPH) respectively. Annual percentage change (APC) was used to
      measure the changes in rates over time. RESULTS: 1637 new cases of oral cancer
      were registered in the CPCR and the mean age upon diagnosis was 60 years. The
      ASIR decreased from 1962-2007 in men APC= 1.3 (IC95%:-2.0; -0.6) and women APC= 
      1.0 (IC95%: -1.7; -0.4).The ASMR decreased from 1984-2001 only in men, APC=2.8
      (IC95%: -4.1; -1.5). CONCLUSIONS: There was a significant decrease in the
      incidence and mortality rates for OC in Cali, Colombia. The type of tumor
      associated to these changes was the squamous cell carcinoma.

PMID- 25604294
TI  - [Cancer mortality trends in Mexico, 1980-2011].
AB  - OBJECTIVE: To evaluate trends in cancer mortality in Mexico between 1980-2011.
      MATERIAL AND METHODS: Through direct method and using World Population 2010 as
      standard population, mortality rates for all cancers and the 15 most frequent
      locations, adjusted for age and sex were calculated. Trends in mortality rates
      and annual percentage change for each type of cancer were estimated by joinpoint
      regression model. RESULTS: As a result of the reduction in mortality from lung
      cancer (-3.2% -1.8% in men and in women), stomach (-2.1% -2.4% in men and in
      women) and cervix (-4.7%); since 2004 a significant (~1% per year) decline was
      observed in cancer mortality in general, in all ages, and in the group of 35-64
      years of both sexes. Other cancers such as breast and ovarian cancer in women; as
      well as for prostate cancer in men, showed a steady increase. CONCLUSIONS: Some
      of the reductions in cancer mortality may be partially attributed to the
      effectiveness of prevention programs. However, adequate records of population
      based cancer are needed to assess the real impact of these programs; as well as
      designing and evaluating innovative interventions to develop more cost-effective
      prevention policies.

PMID- 25604295
TI  - Cost of the Cervical Cancer Screening Program at the Mexican Social Security
      Institute.
AB  - OBJECTIVE: To estimate the annual cost of the National Cervical Cancer Screening
      Program (CCSP) of the Mexican Institute of Social Security (IMSS). MATERIALS AND
      METHODS: This cost analysis examined regional coverage rates reported by IMSS. We
      estimated the number of cytology, colposcopy, biopsy and pathology evaluations,
      as well as the diagnostic test and treatment costs for cervical intraepithelial
      neoplasia grade II and III (CIN 2/3) and cervical cancer. Diagnostic test costs
      were estimated using a micro-costing technique. Sensitivity analyses were
      performed. RESULTS: The cost to perform 2.7 million cytology tests was nearly 38
      million dollars, which represents 26.1% of the total program cost (145.4
      million). False negatives account for nearly 43% of the program costs.
      CONCLUSION: The low sensitivity of the cytology test generates high rates of
      false negatives, which results in high institutional costs from the treatment of
      undetected cervical cancer cases.

PMID- 25604296
TI  - [Early detection of breast and cervical cancer among indigenous communities in
      Morelos, Mexico].
AB  - OBJECTIVE: To analyze the perception in relation to when and how to perform
      actions for the early detection of breast and cervical cancer among women and
      health care providers in communities with a high percentage of indigenous
      population in Morelos, Mexico. MATERIALS AND METHODS: Ten health providers and 58
      women users of health services were interviewed which have a first level of
      attention in five communities. The analysis was developed under the approach of
      the Grounded Theory. RESULTS: Providers are poorly informed about current
      regulations and specific clinical indications for the detection of cervical and
      breast cancer. Few practice health literacy under intercultural sensitization.
      The users have imprecise or wrong notions of the early detection. CONCLUSIONS:
      The need for training in adherence to norms is evident. It is urgent to assume a
      culturally relevant approach to enable efficient communication and promote health
      literacy for early detection of these two cancers.

PMID- 25604297
TI  - [Counseling for HPV detection when used to screen for cervical cancer: a
      qualitative study on the needs of women from Michoacan, Mexico].
AB  - OBJECTIVE: To explore the information and counseling needs of a group of Mexican
      women during use of the HPV test. MATERIALS AND METHODS: In 2011, 24
      semistructured interviews were done with women upon receiving HPV test results in
      two municipalities in the state of Michoacan. Qualitative analysis of the
      interviews was done using constant comparison techniques. RESULTS: During their
      use of screening services women received limited counseling; they felt anguish
      and confusion. Women were interested in receiving information and advice on HPV
      and cervical cancer, the meaning of test result, next steps to be taken in their
      healthcare use as well as information and emotional support related to the sexual
      transmission of HPV. CONCLUSIONS: The design and implementation of policies are
      needed which instigate health education and counseling in conjunction with HPV
      testing.

PMID- 25604298
TI  - [Breast cancer screening process indicators in Mexico: a case study].
AB  - OBJECTIVE: To identify, measure and compare the performance indicators of
      productivity, effective access and quality service for the early detection breast
      cancer program in Mexico. MATERIAL AND METHODS: By means of a study case based on
      the 2011 Women Cancer Information System (SICAM), the indicators were measured
      and compared with the Mexican official standard NOM-041-SSA2-2011 and
      international standards. RESULTS: The analysis showed insufficient installed
      capacity (37%), low coverage in screening (15%), diagnostic evaluation (16%),
      biopsy (44%) and treatment (57%), and very low effectiveness in confirmed cases
      by the total number of screening mammograms performed (0.04%). There was no
      information available, from SICAM, to estimate the rest of the indicators
      proposed. CONCLUSIONS: Efficient health information systems are required in order
      to monitor indicators and generate performance observatories of screening
      programs.

PMID- 25604299
TI  - [Correct utilization of breast cancer detection techniques in Mexican women].
AB  - OBJECTIVE: Identify the characteristics associated with correct utilization of
      self examination (SE), clinical exam (CE) and mammography (MA) for breast cancer
      (BC) early detection. MATERIALS AND METHODS: Interviews were undertaken with 1
      030 Mexican women (n=1 030), 20 to 88 years of age, regarding their reproductive
      and sociodemographic characteristics. An index of correct utilization was
      constructed based on the form and frequency practice of those techniques.
      RESULTS: The prevalence of correct utilization of SE was 11% and 5.4% for CE.
      Further, 7.6% of women 40-49 years of age with 2 or more BC risk factors had MA
      during the two years prior to the interview, and for 31.6% among women >=50 years
      of age the MA was annually. The main determinant of MA utilization was having
      financial protection from either IMSS, ISSSTE or Seguro Popular. CONCLUSIONS: It
      is necessary to improve the correct utilization of BC detection techniques in
      Mexico.

PMID- 25604300
TI  - Breast cancer in Latin America: global burden, patterns, and risk factors.
AB  - Breast cancer is a major public health problem in Latin America (LA) and the most
      common form of cancer among women. An important variability according to
      ethnicity/race with respect to incidence/mortality, clinical characteristics, and
      prognosis is observed throughout LA. In addition, women are more likely to
      develop breast cancer (BC) at younger age and to be diagnosed at an advanced
      stage compared to western women. While little is known about specific risk
      factors, changes in reproductive pattern (parity, breastfeeding) and lifestyle
      factors including sedentary behaviours, unhealthy diet, and alcohol intake may
      contribute to the increase of BC incidence. In this paper we give an overview of
      the burden and patterns of BC, review the leading causes of BC and discuss the
      possible ways to improve BC prevention and control in LA. 

PMID- 25604301
TI  - [Diet and gastric cancer in Mexico and in the world].
AB  - Gastric cancer (GC) is the fourth leading cause of cancer death at global level.
      Diet, alcohol and tobacco, in addition to Helicobacter pylori infection, account
      for a large number of cases. Some substances contained in foods may influence GC
      carcinogenesis process; however, the underlying mechanisms have not been fully
      elucidated. In Mexico and worldwide, a low intake of fruits, non-starchy and
      allium vegetables, pulses, and foods containing selenium, as well as high intake
      of salt, salty, salted and smoked foods, chili pepper, processed and
      grilled/barbecued meats, have been respectively associated with an increased risk
      of GC. Based on the available evidence, programs for GC prevention and control
      could be developed and evaluated.

PMID- 25604302
TI  - [In memoriam. Adonis de Carvalho].

PMID- 25604305
TI  - [Vascular management in anatomical liver resection].
AB  - The vascular management in anatomical liver resection plays a pivotal role in
      maintaining an adequately functional residual liver volume. In this respect it is
      essential to guarantee an adequate portal and arterial inflow as well venous
      outflow for the whole residual liver (lobe or segments). To achieve this, the
      liver surgeon should have excellent perioperative imaging, surgical expertise
      based on knowledge of vascular anatomy, physiology and hemodynamics of the liver
      and a well-designed and cautious operative strategy. The use of intraoperative
      ultrasonography (with or without contrast enhancement) and modern parenchymal
      dissectors (e.g. ultrasound or water jet dissectors) are strongly recommended. 

PMID- 25604304
TI  - Individual and contextual factors related to dental caries in underprivileged
      Brazilian adolescents.
AB  - BACKGROUND: Investigate the individual and contextual variables related to caries
      in underprivileged adolescents, and the disparity in distribution of the disease.
      METHODS: Cross-sectional analytical study, conducted in the city of Piracicaba,
      SP, Brazil, in 2012. The probabilistic sample was composed of 1,179 adolescents
      from 15-19 years of age, randomly selected from 21 state schools and 34 Primary
      Health Units--Family Health (PHU-FH). The dependent variables studied were number
      of decayed teeth and caries experience (DMFT). The independent variables were
      classified into individual (clinical, sociodemographic, psychosocial, self
      perception, impact on oral health, access to services, and quality of life) and
      contextual (social exclusion index, total number of residents in suburb, literacy
      rate, and the following variables given in percentages: residences in the home
      ownership category, provision of domestic sewerage, trash collection, families
      with income of over 1 minimum wage per month, and families without monthly
      income) variables. The multilevel regression model was estimated by the PROC
      GLIMMIX (Generalized Linear Models-Mixed) procedure, considering the individual
      variables as Level 1 and the contextual variables of the suburbs as Level 2.
      Adjustment of the model was evaluated by -2 Res Log Likelihood with alpha = 0.05.
      RESULTS: As regards the individual variables, adolescents who declared having a
      prison inmate in the Family and resided in homes with a larger number of persons,
      showed a higher number of decayed teeth. There were a larger number of decayed
      teeth, a higher DMFT value, and worse self-perception as regards the health of
      their teeth and mouth. Other variables, such as being of the female gender, age
      and time since last visit to the dentist were related to the DMFT index. As
      regards the contextual variables, the DMFT was lower in suburbs with greater
      access to domestic sewage, and the number of decayed teeth was higher in suburbs
      with the worst social exclusion indices. CONCLUSION: Individual and contextual
      variables were associated with the presence of caries and DMFT index in
      underprivileged adolescents, indicating that they must be taken into
      consideration in the formulation of policies directed towards oral health
      promotion and prevention activities in this group.

PMID- 25604306
TI  - [Complication management after liver transplantation. Increasing patient safety
      by standardized approach and interdisciplinary cooperation].
AB  - The interdisciplinary management of postoperative complications in liver
      transplantation is of extreme importance. Due to organ shortage and
      prioritization of the most severely ill recipients in the model for end-stage
      liver disease (MELD)-based allocation, both donor and recipient associated
      morbidity are increasing. An interdisciplinary, structured monitoring concept is
      essential for the timely identification and specific treatment of postoperative
      complications. Interdisciplinary clinical rounds, laboratory testing and Doppler
      ultrasound monitoring of the graft perfusion are as important as comprehensive
      anti-infection prophylaxis and immunosuppression. Arterial perfusion disorders of
      any kind, biliary complications and postoperative fluid accumulation demand
      individualized therapeutic concepts. In summary, the success of liver
      transplantation depends on the communication and coordinated interdisciplinary
      cooperation of all disciplines involved. 

PMID- 25604307
TI  - [Operation time for suprapubic transumbilical cholecystectomy: Results of a
      prospective randomized trial].
AB  - BACKGROUND: Over the last decade new innovative minimally invasive techniques
      (e.g. transvaginal cholecystectomy and single incision laparoscopic
      cholecystectomy) have been developed to reduce operative trauma, postoperative
      pain and to achieve better cosmetic results. Nevertheless, most of these
      techniques are more difficult and time-consuming than conventional laparoscopic
      cholecystectomy (CLC). A new approach, the Minden technique for combined
      suprapubic transumbilical cholecystectomy (MI-CHE) has been proven to provide a
      very good cosmetic outcome with reduced operative trauma. The aim of this study
      was to survey whether MI-CHE prolongs operation times to a relevant degree
      compared to CLC. METHODS: A total of 40 patients undergoing laparoscopic
      cholecystectomy were randomized between both techniques. The duration of the
      operation and other perioperative data were recorded. Surgery was performed by
      four resident surgeons who had not yet performed any technique of laparoscopic
      cholecystectomy, neither MI-CHE nor CLC but were assisted by the same senior
      staff surgeon in all cases. The two patient groups showed no differences in age,
      gender and body mass index. The study was registered (DRKS00003271). Non
      inferiority was tested using 95% confidence intervals (95% CI). RESULTS: The mean
      operation time was shorter by - 4.2 min (95% CI, + 6.4 min to - 14.8 min) in the
      MI-CHE as compared to the CLC group (65.5 min versus 69.7 min). There were no
      open conversions but in one patient intestinal injury occurred during the
      umbilical mini-laparotomy. There were no differences in patient satisfaction and
      perioperative pain between both procedures. CONCLUSION: The MI-CHE, which
      provides very good cosmetic results, is not more time-consuming than CLC.
      Additionally, it seems to be safe and not more difficult to learn than CLC.

PMID- 25604308
TI  - Right vertical infra-axillary thoracotomy for double valve replacement.
AB  - This study reviews the experience with a right vertical infra-axillary
      thoracotomy (RVIAT) for double valve replacement (DVR).

PMID- 25604309
TI  - Novel poly (ADP-ribose) polymerase inhibitor, AZD2281, enhances radiosensitivity
      of both normoxic and hypoxic esophageal squamous cancer cells.
AB  - Radiotherapy plays an important role in the treatment of esophageal squamous cell
      carcinoma (ESCC). However, the outcome of radiotherapy in ESCC remains
      unsatisfactory because esophageal squamous cancer cells, particularly those under
      hypoxic condition, exhibit radioresistance. The aim of this study was to
      determine whether or not AZD2281, a potent poly (ADP-ribose) polymerase (PARP)
      inhibitor, could enhance the radiation sensitivity of two ESCC cell lines, namely
      ECA109 and TE13. The radiosensitizing effect of AZD2281 was evaluated on the
      basis of cell death, clonogenic survival and tumor xenograft progression. AZD2281
      alone was slightly toxic to ESCC cell lines. Apoptosis was increased and
      clonogenic survival was decreased in both cell lines when AZD2281 was combined
      with ionizing radiation (IR) under normoxic condition. AZD2281 enhanced IR
      induced apoptosis to a more significant level under chronic hypoxic condition
      (0.2% O(2), 48 hour) than under normoxic condition. AZD2281 also slightly
      enhanced clonogenic cell death under chronic hypoxic condition compared with that
      under normoxic condition. This result could be associated with increased
      radiation-induced DNA double-strand breaks (DSB), decreased DSB repair and
      increased apoptosis of ESCC cells. Furthermore, homologous recombination (HR)
      protein Rad51 expression and focus formation were decreased in ESCC cells exposed
      to moderate chronic hypoxic condition (0.2% O(2), 48 hour); this result indicated
      that chronic hypoxic ESCC cells were HR deficient, possibly causing contextual
      synthetic lethality with PARP inhibitor in radiation sensitization. AZD2281 was
      also a radiation sensitizer in ESCC tumor xenograft models. Hence, in vitro and
      in vivo findings provide evidence that AZD2281 potently sensitizes ESCC cells to
      X-ray irradiation. The selective cell killing of HR-defective hypoxic cells
      contributes to radiosensitization by PARP inhibitor in ESCC cells under hypoxic
      condition.

PMID- 25604311
TI  - Aldosterone deficiency after unilateral adrenalectomy for Conn's syndrome: a case
      report and literature review.
AB  - INTRODUCTION: Approximately 35% of cases of Conn's syndrome (primary
      aldosteronism) result from a solitary functioning adrenal adenoma, and these
      patients are best managed by adrenalectomy. Postoperative hypoaldosteronism after
      unilateral adrenalectomy is uncommon. CASE PRESENTATION: We present a case and
      literature review of hypoaldosteronism after unilateral adrenalectomy for Conn's
      syndrome, which demonstrates the insidious and sometimes delayed presentation.
      DISCUSSION: In this clinical case we summarize the previously published cases of
      post-adrenalectomy hypoaldosteronism based on a PUBMED and EBSCOhost search of
      all peer-reviewed publications (original articles and reviews) on this topic. A
      few cases of aldosterone insufficiency post-adrenalectomy for Conn's syndrome
      were identified. The etiological factors for prolonged selective suppression of
      aldosterone secretion after unilateral adrenalectomy remain unclear. CONCLUSION:
      It is important to be aware of the risk of postoperative hypoaldosteronism in
      this patient population. Close postoperative follow-up is necessary and strongly
      recommended, especially in patients with certain risk factors. Patients may need
      mineralocorticoid supplementation during this period.

PMID- 25604310
TI  - Prevalence of pfhrp2 and pfhrp3 gene deletions in Puerto Lempira, Honduras.
AB  - BACKGROUND: Recent studies have demonstrated the deletion of the histidine-rich
      protein 2 (PfHRP2) gene (pfhrp2) in field isolates of Plasmodium falciparum,
      which could result in false negative test results when PfHRP2-based rapid
      diagnostic tests (RDTs) are used for malaria diagnosis. Although primary
      diagnosis of malaria in Honduras is determined based on microscopy, RDTs may be
      useful in remote areas. In this study, it was investigated whether there are
      deletions of the pfhrp2, pfhrp3 and their respective flanking genes in 68 P.
      falciparum parasite isolates collected from the city of Puerto Lempira, Honduras.
      In addition, further investigation considered the possible correlation between
      parasite population structure and the distribution of these gene deletions by
      genotyping seven neutral microsatellites. METHODS: Sixty-eight samples used in
      this study, which were obtained from a previous chloroquine efficacy study, were
      utilized in the analysis. All samples were genotyped for pfhrp2, pfhrp3 and
      flanking genes by PCR. The samples were then genotyped for seven neutral
      microsatellites in order to determine the parasite population structure in Puerto
      Lempira at the time of sample collection. RESULTS: It was found that all samples
      were positive for pfhrp2 and its flanking genes on chromosome 8. However, only
      50% of the samples were positive for pfhrp3 and its neighboring genes while the
      rest were either pfhrp3-negative only or had deleted a combination of pfhrp3 and
      its neighbouring genes on chromosome 13. Population structure analysis predicted
      that there are at least two distinct parasite population clusters in this sample
      population. It was also determined that a greater proportion of parasites with
      pfhrp3-(and flanking gene) deletions belonged to one cluster compared to the
      other. CONCLUSION: The findings indicate that the P. falciparum parasite
      population in the municipality of Puerto Lempira maintains the pfhrp2 gene and
      that PfHRP2-based RDTs could be considered for use in this region; however
      continued monitoring of parasite population will be useful to detect any
      parasites with deletions of pfhrp2.

PMID- 25604313
TI  - Intensive Atorvastatin Therapy Attenuates the Inflammatory Responses in Monocytes
      of Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention
      via Peroxisome Proliferator-Activated Receptor gamma Activation.
AB  - Periprocedural myocardial injury is a prognostically important complication of
      percutaneous coronary intervention (PCI). However, it still remains unclear
      whether and how intensive atorvastatin therapy attenuates the unfavorable
      inflammatory responses of monocytes associated with PCI. The aim of the study was
      to investigate the impact of intensive atorvastatin therapy on inflammatory
      responses of monocytes in Chinese patients with unstable angina who received PCI
      in order to explore the potential anti-inflammatory mechanism. Ninety-six
      patients with unstable angina were randomly assigned to atorvastatin 80 mg
      (intensive) or atorvastatin 20 mg (conventional) treatment at a 1:1 ratio.
      Creatine kinase MB (CK-MB), cTnI, hs-CRP, and IL-6 were assessed, and circulating
      CD14(+) monocytes were simultaneously obtained using CD14 MicroBeads 2 h before
      and 24 h after PCI. Plasma levels of CK-MB, cTnI, hs-CRP, and IL-6 were higher in
      the conventional dose group versus those in the intensive dose group following
      PCI. Furthermore, intensive atorvastatin treatment markedly reduced the
      expressions and responses of Toll-like receptor 2 (TLR2), TLR4, and CCR2 of
      CD14(+) monocytes versus the conventional dose group and significantly increased
      the activated peroxisome-proliferator-activated receptor (PPAR) gamma in the
      CD14(+) monocytes post-PCI. Notably, the changes in responses of TLR2, TLR4, and
      CCR2 of CD14(+) monocytes between the two groups were all reversed by PPARgamma
      antagonist and augmented by PPARgamma agonist. In conclusion, a single high (80
      mg) loading dose of atorvastatin reduced the inflammatory response in Chinese
      patients with unstable angina following PCI. The anti-inflammatory role of
      intensive atorvastatin was possibly due to attenuation of inflammatory response
      in monocytes via PPARgamma activation. 

PMID- 25604314
TI  - Adhesion, cohesion, and friction estimated from combining cutting and peeling
      test results for thin noodle sheets.
AB  - The aim of this study was to estimate the adhesive and cohesive fracture
      energies, and frictional characteristics of 7 types of cooked starch and flour
      sheets and combine these into a model framework for textural analysis. Cutting
      tests with wires of diameter 0.30 to 0.89 mm were performed with and without
      lubrication. Plots of the work done, normalized to the area cut by the wire,
      showed that this to be linearly related to wire diameter irrespective of
      lubrication. The oil had little impact on the intercept of these plots, giving
      cohesive fracture energy (Gc ) ranges for these foods between 6.8 and 32.5 J/m(2)
      . However, lubrication had a strong influence on the slope of the plots. From a
      comparison of the slopes for lubricated versus unlubricated tests, the kinetic
      coefficient of friction MUkcould be calculated. Values for MUk between 0.007 and
      0.521 for different foods were obtained. Peeling tests were performed by lifting
      sheets vertically away from a fresh mica surface. The adhesive fracture energy Ga
      , varied from 2.5 to 4.8 J/m(2) . The results can be modeled by plotting the
      ratio of cohesive to adhesive fracture energy against the coefficient of
      friction. Thresholds in both axes suggest a physical basis for distinguishing
      textural perceptions. However, sensory testing with 12 subjects using the 7 food
      types could not establish whether this framework, however well-established
      physically, would apply to oral sensations. A much larger test would be required.

PMID- 25604315
TI  - A Hybrid Quantum Mechanical Approach: Intimate Details of Electron Transfer
      between Type-I CdSe/ZnS Quantum Dots and an Anthraquinone Molecule.
AB  - We report a hybrid computational approach to calculate electron transfer between
      a type-I CdSe/ZnS core/shell quantum dot (QD) with a varying shell thickness and
      the functionalized anthraquinone (AQ) molecule. This novel approach combines the
      traditional electron/hole confinement theory in the effective mass approximation
      for the QD and molecular orbital theory for the AQ molecule. In the present
      study, the QD's electron and hole envelope wave functions are solutions of the
      effective-mass Schrodinger equation, and the AQ wave function is obtained at the
      density functional level. Electron-transfer rate calculations are based on
      Marcus's theory with the coupling strength computed according to an one-electron
      orbital perturbation model. We show that in a heptane solution, the LUMO of AQ
      and the 1Se electron orbital of QD are involved in the charge separation (CS)
      process. The charge recombination (CR) process, on the other hand, occurs from
      the singly occupied molecular orbital of the AQ radical (which corresponds to the
      LUMO in AQ) to a trapped hole state of the QD within the band gap. The
      calculations support previously reported interpretations of the role of the ZnS
      shell as a hindrance in the CS and CR process. 

PMID- 25604312
TI  - Trichostatin A Protects Against Experimental Acute-on-Chronic Liver Failure in
      Rats Through Regulating the Acetylation of Nuclear Factor-kappaB.
AB  - Histone deacetylase inhibitors (HDACi) were recently shown to suppress
      inflammatory responses in experimental models of autoimmune and inflammatory
      diseases. In this study, the protective effects of Trichostatin A (TSA), an
      HDACi, on experimental acute-on-chronic liver failure (ACLF) in rat were
      explored. An ACLF model was established in rats, and animals were randomly
      divided into control, model, and TSA-treated groups. The rats in TSA-treated
      group received TSA (2 mg/kg) at 2 h before induction of ACLF. Samples were
      obtained at 24 h after ACLF induction. We found that the rats in model group
      showed severe damage to liver tissue at 24 h after ACLF induction. TSA improved
      liver injury effectively. Serum tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma (IFN-gamma), interleukin (IL)-10, and IL-18 levels were
      significantly increased in model group compared with control group, but TSA
      reduced serum TNF-alpha, IFN-gamma, IL-10, and IL-18 levels effectively compared
      with model group. In addition, TSA reduced the total HDAC activity, promoted the
      acetylation of histone, and decreased the expressions of class I HDAC in liver
      tissue. TSA also increased the acetylation levels and decreased phosphorylation
      levels in NF-kappaB p65. The median survival time of the rats was significantly
      prolonged in TSA-treated group. To conclude, TSA can inhibit the release of
      multiple inflammatory cytokines, prolong the survival time, and protect against
      ACLF in rats. The mechanisms were probably through enhancing the acetylation
      levels of non-histones rather than histone. 

PMID- 25604316
TI  - Comparison of tocilizumab as monotherapy or with add-on disease-modifying
      antirheumatic drugs in patients with rheumatoid arthritis and inadequate
      responses to previous treatments: an open-label study close to clinical practice.
AB  - This was an exploratory analysis comparing the safety and efficacy of tocilizumab
      monotherapy with those of tocilizumab in combination with disease-modifying anti
      rheumatic drugs (DMARDs). Data were from a single-arm, nonrandomized, open-label,
      24-week study in patients with rheumatoid arthritis in which patients with
      inadequate responses to DMARDs or tumor necrosis factor-alpha inhibitors received
      tocilizumab 8 mg/kg intravenously every 4 weeks plus methotrexate/other DMARD(s)
      combination therapy. If they were intolerant of methotrexate/other DMARD,
      patients received tocilizumab monotherapy. Effectiveness endpoints included
      American College of Rheumatology (ACR) responses (ACR20/50/70/90) and disease
      activity score using 28 joints (DAS28). Of 1,681 patients, 239 received
      tocilizumab monotherapy, and 1,442 received combination therapy. Methotrexate was
      the most common DMARD (79%) used in combination therapy. The frequency of adverse
      events (AEs), serious AEs, and AEs leading to withdrawal were similar between
      tocilizumab monotherapy (82.4, 7.9, and 5.4%, respectively) and combination
      therapy (76.6, 7.8, and 5.1%, respectively). No differences in ACR20/50/70/90
      responses were observed between treatment groups (66.9%/43.5%/23.8%/10.0% vs
      66.9%/47.2%/26.8%/8.5%, respectively; p > 0.12 for all individual comparisons,
      including ACR50 propensity score analyses). The decrease in DAS28 was also
      similar between treatment groups (mean +/- standard deviation: -3.41 +/- 1.49 for
      tocilizumab monotherapy vs -3.43 +/- 1.43 for combination therapy; p > 0.33 all
      analyses, including propensity score analyses). Tocilizumab had a comparable
      safety profile, and was similarly effective, when used as monotherapy or in
      combination with DMARDs in a broad population of patients with rheumatoid
      arthritis.

PMID- 25604317
TI  - Methotrexate as combination partner of TNF inhibitors and tocilizumab. What is
      reasonable from an immunological viewpoint?
AB  - The goal of therapy of rheumatoid arthritis is to achieve a remission or at least
      low disease activity. TNF inhibitors induce high remission rates only in
      combination with methotrexate, whereas the efficacy of tocilizumab is optimal
      even as a monotherapy. In this article, the differing dependence of the
      biological drugs on methotrexate is explained from the viewpoint of an
      immunologist. A selective search and evaluation of the literature was performed
      with regard to the mode of action of TNF inhibitors, tocilizumab and methotrexate
      in rheumatoid arthritis. Methotrexate primarily inhibits the activation and
      proliferation of lymphocytes. TNF inhibitors suppress monocytes and myeloid
      dendritic cells, and tocilizumab has a broader activity and is directed against
      both the lymphoid as well as the myeloid compartment. In view of the broad mode
      of action of tocilizumab, it can be explained why this drug, in contrast to TNF
      inhibitors, is acting optimally even in monotherapy.

PMID- 25604318
TI  - When uncommon and common coalesce: adult onset Still's disease associated with
      breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).
AB  - Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto
      inflammatory disorder, while breast augmentation is a very common cosmetic
      procedure. We describe a case in which these two coalesce, AOSD, manifested with
      pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic,
      missing link, behind the development of AOSD following mammoplasty, is thought to
      be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We
      reviewed other cases of AOSD associated with breast mammoplasty published to date
      and the literature regarding AOSD and ASIA syndrome. The review is followed by a
      short debate of whether silicone implants should be explanted in similar, future
      cases. 

PMID- 25604320
TI  - Innate lymphoid cells involve in tumorigenesis.
AB  - Innate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen
      exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were
      recently categorized as being of the lymphoid lineage and have been classified
      into three groups. ILCs play important roles in immunity against pathogens, and
      an anti-tumor immune-related function was recently demonstrated. In this review
      we discuss whether and how ILCs involve in the tumorigenesis, providing new
      insights into the mechanisms underlying the particular functions of ILCs as well
      as the potential targets for tumor intervention. 

PMID- 25604319
TI  - The correlation between radiographic knee OA and clinical symptoms--do we know
      everything?
AB  - This study aims to evaluate the correlations between common clinical
      osteoarthritis (OA) diagnostic tools in order to determine the value of each. A
      secondary goal was to investigate the influence of gender differences on the
      findings. Five hundred and eighteen patients with knee OA were evaluated using
      the Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire,
      short form 36 (SF-36) Health Survey, and plain radiographs. Analysis of variance
      (ANOVA) was used to compare the different domains of the WOMAC and SF-36
      questionnaires between genders and the radiographic scale. Higher knee OA x-ray
      grade were associated with worse clinical outcome: for women, higher scores for
      the WOMAC pain, function and final scores and lower scores in the SF-36 final
      score; in men, lower SF-36 overall and physical domains scores. Gender
      differences were found in all clinical scores that were tested, with women having
      worse clinical scores for similar radiographic grading (p values <0.001). Knee
      radiographs for OA have an important role in the clinical evaluation of the
      patient. Patients with higher levels of knee OA in x-ray have a higher
      probability of having a worse clinical score in the WOMAC and SF-36 scores. The
      gender differences suggest that for similar knee OA x-ray grade, women's clinical
      scores are lower. TRIAL REGISTRATION: NCT00767780.

PMID- 25604322
TI  - Experimental study of a new open stent for vessel banding in a swine model: long
      term results.
AB  - AIM: A new stent was designed, conceived for being placed externally around blood
      vessels to perform vessel banding in a much simple and fast way. In fact it
      requires the dissection of a single segment of the aortic wall, as its mechanical
      features allow it to slide on the tunica adventitia. After previous tests (ex
      vivo and in vivo test), the new stent has been evaluated in vivo long-term study.
      METHODS: In female pig of average weight of 60 kg, after placement of
      endoprosthesis in infrarenal abdominal aorta, immediately below renal arteries,
      aortic banding was performed with new stent at the level of each end of
      endoprosthesis, identified under fluoroscopic guidance. Pigs were followed up for
      six months, and acetylsalicylic acid was administrated: 100 mg once a day. After
      six months, histological evaluation of explanted abdominal aorta was performed.
      RESULTS: New stent made the aortic banding simple and fast. Postoperative course
      was uneventful. Histological results were similar to previous 10-week survival
      tests and not damages of aortic wall were observed. CONCLUSION: Positive outcome
      of three last long-term survival tests, as of all those ex vitro and in vivo
      tests previously performed, makes conceivable further scientific investigation
      and trials.

PMID- 25604321
TI  - The Alcohol Use Disorder and Associated Disabilities Interview Schedule-5
      (AUDADIS-5): procedural validity of substance use disorders modules through
      clinical re-appraisal in a general population sample.
AB  - BACKGROUND: The purpose of this study was to assess the procedural validity of
      the substance disorder modules of the lay-administered Alcohol Use Disorder and
      Associated Disabilities Interview Schedule, Diagnostic and Statistical Manual of
      Mental Disorders, Fifth Edition (DSM-5) Version (AUDADIS-5) through clinician re
      appraisal re-interviews. METHODS: The study employed a test-retest design among
      712 respondents from the National Epidemiologic Survey on Alcohol and Related
      Conditions-III (NESARC-III). A clinician-administered, semi-structured interview,
      the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5
      version (PRISM-5) was used as the re-appraisal. Kappa coeffients indicated
      concordance of the AUDADIS-5 and PRISM-5 for DSM-5 substance use disorder
      diagnoses, while intraclass correlation coefficients (ICC) indicated concordance
      on dimensional scales indicating the DSM-5 criteria count for each disorder.
      RESULTS: With few exceptions, concordance of the AUDADIS-5 and the PRISM-5 for
      DSM-5 diagnoses of substance use disorders ranged from fair to good (kappa=0.40
      0.72). Concordance on dimensional scales was excellent (ICC>=0.75) for the
      majority of DSM-5 SUD diagnoses, and fair to good (ICC=0.43-0.72) for most of the
      rest. CONCLUSIONS: As indicated by concordance with a semi-structured clinician
      administered re-appraisal, the procedural validity of the AUDADIS-5 DSM-5
      substance use disorder diagnoses found in this study indicates that these AUDADIS
      5 diagnoses are useful tools in epidemiologic studies. The considerably stronger
      concordance of the AUDADIS-5 and PRISM-5 dimensional DSM-5 SUD measures supports
      a current movement to place more emphasis on dimensional measures of
      psychopathology, and suggests that such measures may be more informative than
      binary diagnoses for research, and possibly for clinical purposes as well.

PMID- 25604323
TI  - Chronic type B aortic dissection: indications and strategies for treatment.
AB  - Chronic type B aortic dissection is a distinctive condition that needs individual
      treatment strategies and different considerations than in therapy of acute or
      subacute type B aortic dissection. The most common indication for treatment of
      this complex disease is aneurysmal dilatation of the dissected aortic segment.
      While open repair of the enlarged dissected aorta remains the best option for
      good-risk patients and patients with connective tissue disorders in high-volume
      centers with respective expertise, endovascular management of chronic type B
      aortic dissection with postdissection aneurysms has significantly gained ground
      in the past years. But the concept of TEVAR with implantation of a tubular stent
      graft into the thoracic aorta to seal the proximal entry tear and reroute the
      blood flow into the true lumen alone, is not associated with satisfactory
      results. This is mainly due to the sparse remodeling capacity of the aortic
      tissue compared to earlier stages of the disease as the aortic wall and the
      dissection membrane are thickened and more rigid. On the other hand, it is
      restricted by the most limiting factor for endovascular success in chronic type B
      aortic dissection: persistent false lumen perfusion. This problem also affects
      patients with residual dissection after surgical repair of a DeBakey type I
      aortic dissection or dissection after ascending aortic repair for other
      pathologies. Hence, it is evident that strategies to achieve endovascular false
      lumen occlusion are of increasing importance and novel techniques have been
      introduced to solve the problem of persisting false lumen flow. Thus, the
      evolution of a large variety of techniques to address the false lumen perfusion
      issue indicates that complicated chronic type B dissection involves a high
      diversity in clinical presentation and morphology. A large armamentarium of
      catheter skills as well as critical individualized treatment strategies are
      required to address the heterogenous morphological disease pattern for each
      individual patient. The rapid development in endovascular techniques gives new
      directions for treatment indications and strategies in chronic aortic dissection
      and enables new insights into this old disease. 

PMID- 25604324
TI  - Burnout in emergency department healthcare professionals is associated with
      coping style: a cross-sectional survey.
AB  - INTRODUCTION: Ineffective coping may lead to impaired job performance and
      burnout, with adverse consequences to staff well-being and patient outcomes. We
      examined the relationship between coping styles and burnout in emergency
      physicians, nurses and support staff at seven small, medium and large emergency
      departments (ED) in a Canadian health region (population 500,000). METHODS:
      Linear regression with the Coping Inventory for Stressful Situations (CISS) and
      Maslach Burnout Inventory (MBI) was used to evaluate the effect of coping style
      on levels of burnout in a cross-sectional survey of 616 ED staff members. CISS
      measures coping style in three categories: task-oriented, emotion-oriented and
      avoidance-oriented coping; MBI, in use for 30 years, assesses the level of
      burnout in healthcare workers. RESULTS: Task-oriented coping was associated with
      decreased risk of burnout, while emotion-oriented coping was associated with
      increased risk of burnout. DISCUSSION: Specific coping styles are associated with
      varied risk of burnout in ED staff across several different types of hospitals in
      a regional network. Coping style intervention may reduce burnout, while leading
      to improvement in staff well-being and patient outcomes. Further studies should
      focus on building and sustaining task-oriented coping, along with alternatives to
      emotion-oriented coping.

PMID- 25604325
TI  - Tracheal intubation related complications in the prehospital setting.
AB  - BACKGROUND: Prehospital tracheal intubation (TI) is associated with morbidity and
      mortality, particularly in cases of difficult intubation. The goal of the present
      study was to describe factors associated with TI related complications in the
      prehospital setting. METHODS: This was a prospective cohort study including all
      patients intubated on scene in a prehospital emergency medical service over a 4
      year period. TI related complications included oxygen desaturation, aspiration,
      vomiting, bronchospasm and/or laryngospasm, and mechanical complications
      (mainstem intubation, oesophageal intubation and airway lesion- that is, dental
      or laryngeal trauma caused by the laryngoscope). Difficult intubation was defined
      as >2 failed laryngoscopic attempts, or the need for any alternative TI method. A
      multivariate logistic regression was used to identify the risk factors for TI
      related complications. RESULTS: 1251 patients were included; 208 complications
      occurred in 165 patients (13.1%). Among the 208 complications, the most frequent
      were oesophageal intubation (n=69, 29.7%), desaturation (n=58, 25.0%) and
      mainstem intubation (n=37, 15.9%). In multivariate analysis, difficult intubation
      (OR=6.13, 3.93 to 9.54), Cormack and Lehane grades 3 and 4 (OR=2.23, 1.26 to 3.96
      for Cormack and Lehane grade 3 and OR=2.61, 1.28 to 5.33 for Cormack and Lehane
      grade 4 compared with Cormack and Lehane grade 1) and a body mass index >30
      kg/m(2) (OR=2.22, 1.38 to 3.56) were significantly associated with TI related
      complications. CONCLUSIONS: Despite specific guidelines, TI related complications
      are more frequent in the prehospital setting when intubation is deemed difficult,
      the Cormack and Lehane grade is greater than grade 1 and the patient is
      overweight. In such situations, particular attention is needed to avoid
      complications.

PMID- 25604326
TI  - [Heterozygote forms of familial Mediterranean fever can be manifested in adults
      as myofacial pain syndrome].
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is a disease characterized by
      recurrent fever, serositis, arthritis and unspecific myalgia. It is prevalent
      among Mediterranean people and has been shown to be associated with mutations in
      the Mediterranean fever (MEFV) gene which, encodes pyrin a regulatory protein of
      the inflammasome. As heterozygous mutations in MEFV can be associated with only
      mild inflammatory symptoms, such as arthralgia or chronic fibromyalgic pain, FMF
      may be underdiagnosed in the current diagnostic work-up of musculoskeletal
      diseases. METHODS: The selection of patients was carried out according to the
      following criteria: myofacial pain syndrome, seronegative oligoarthralgia, a
      slight inflammatory constellation and ethnic origin from the Mediterranean area.
      When these criteria were fulfilled a molecular genetic investigation was carried
      out RESULTS: This article presents evidence that 9 out of 12 Mediterranean
      patients with recurrent myofascial pain syndrome and mild inflammation revealed
      heterozygote mutations in the MEFV gene and 7 of these patients benefitted from
      treatment with colchicine. DISCUSSION: As colchicine treatment not only improved
      the myofascial pain but also prevented FMF-associated amyloidosis and
      nephropathy, differential diagnosis of fibromyalgia in patients of Mediterranean
      origin should include FMF and a genetic screening of the MEFV locus.

PMID- 25604328
TI  - Visceral leishmaniasis as an independent cause of high immune activation, T-cell
      senescence, and lack of immune recovery in virologically suppressed HIV-1
      coinfected patients.
AB  - OBJECTIVES: Different immune alterations have been described in HIV-infected
      patients with visceral leishmaniasis (VL). We aimed to identify the immunological
      factors involved in the lack of immunological recovery and VL relapses in HIV
      infected patients with VL, by comparison with other HIV-infected patients.
      METHODS: We carried out a cross-sectional study of 55 patients receiving
      suppressive combination antiretroviral therapy (cART) for at least 1 year: nine
      with previous relapsing VL, 20 with an immunodiscordant response (IDR) to cART
      (CD4 count < 200 cells/MUL) and no previous VL, and 26 with a concordant response
      (CR) to cART (CD4 count > 350 cells/MUL) without VL. Immunosenescence was
      investigated by analysing CD57(+) CD28(-) levels, immune activation by analysing
      CD38(+) HLA-DR(+) levels, inflammation by analysing interleukin (IL)-6 levels,
      and microbial translocation by analysing lipopolysaccharide (LPS) and soluble
      CD14 (sCD14) levels. RESULTS: In VL patients, the median time since VL diagnosis
      was 42 months, and all patients had had at least one relapse despite suppressive
      cART for a median time of 43 months. Patients with previously diagnosed VL had a
      higher CD8 T-cell activation level (P < 0.001) than those with IDR. Also, levels
      of IL-6, LPS and especially sCD14, associated with bacterial translocation and
      additional monocyte activation, were significantly increased in patients with
      previous VL compared with patients with IDR (P = 0.048, P = 0.049 and P < 0.001,
      respectively). In addition, patients with previous VL had higher levels of CD8 T
      cell senescence. Notably, the levels of immune activation and inflammation in
      patients with previous VL were not related to the time of VL diagnosis, the
      number of VL relapses, or hepatitis C virus (HCV) coinfection. CONCLUSIONS: Our
      data demonstrate that VL patients had an even worse immunological status than
      patients with IDR, which was probably associated with increased microbial
      translocation and additional monocyte/macrophage activation. These data explain
      the observed lack of immunological recovery and the occurrence of VL relapses in
      HIV-infected patients with previous VL.

PMID- 25604327
TI  - Workflows for automated downstream data analysis and visualization in large-scale
      computational mass spectrometry.
AB  - MS-based proteomics and metabolomics are rapidly evolving research fields driven
      by the development of novel instruments, experimental approaches, and analysis
      methods. Monolithic analysis tools perform well on single tasks but lack the
      flexibility to cope with the constantly changing requirements and experimental
      setups. Workflow systems, which combine small processing tools into complex
      analysis pipelines, allow custom-tailored and flexible data-processing workflows
      that can be published or shared with collaborators. In this article, we present
      the integration of established tools for computational MS from the open-source
      software framework OpenMS into the workflow engine Konstanz Information Miner
      (KNIME) for the analysis of large datasets and production of high-quality
      visualizations. We provide example workflows to demonstrate combined data
      processing and visualization for three diverse tasks in computational MS:
      isobaric mass tag based quantitation in complex experimental setups, label-free
      quantitation and identification of metabolites, and quality control for
      proteomics experiments.

PMID- 25604329
TI  - Epidemiology of posterior heel pain in the general population: cross-sectional
      findings from the clinical assessment study of the foot.
AB  - OBJECTIVE: To identify the population prevalence of posterior heel pain (HP),
      related disability, and associated factors. METHODS: A total of 9,334 adults ages
      >=50 years were mailed a questionnaire. Participants reporting foot pain in the
      last month shaded the foot pain location on a manikin. The Manchester Foot Pain
      and Disability Index assessed disabling foot pain. Population prevalence of any,
      bilateral, and disabling posterior HP was estimated using weighted logistic
      regression accounting for nonresponse. Odds ratios (ORs) and 95% confidence
      intervals (95% CIs) were calculated between posterior HP and age, sex,
      neighborhood deprivation, occupational class (professional, intermediate, and
      manual), body mass index (BMI, kg/m(2) ), physical activity, heel height, and
      diabetes mellitus. RESULTS: A total of 5,109 questionnaires were received
      (adjusted response 56%). Six hundred seventy-five respondents (13%) reported
      posterior HP, of whom 382 had bilateral symptoms. A total of 398 (8%) reported
      disabling posterior HP. Posterior HP in either foot was associated with
      increasing BMI (25.0-29.9 [OR 1.58], 30.0-34.9 [OR 2.13], and >=35.0 [OR 4.09])
      and with manual occupations (OR 1.96, 95% CI 1.47-2.62). Bilateral posterior HP
      was associated with increasing BMI (25.0-29.9 [OR 1.79], 30.0-34.9 [OR 2.43], and
      >=35.0 [OR 5.79]), diabetes mellitus (OR 1.48, 95% CI 1.07-2.05), and manual
      occupations (OR 2.21, 95% CI 1.48-3.30). Disabling posterior HP was associated
      with increasing BMI (25.0-29.9 [OR 1.44], 30.0-34.9 [OR 2.50], and >=35.0 [OR
      4.69]), age (>=75 years OR 1.41, 95% CI 1.01-1.96), manual occupations (OR 1.97,
      95% CI 1.35-2.88), and diabetes mellitus (OR 1.56, 95% CI 1.04-1.95). High
      physical activity was negatively associated with posterior HP in either heel (OR
      0.43, 95% CI 0.33-0.56), bilateral posterior HP (OR 0.35, 95% CI 0.25-0.49), and
      disabling posterior HP (OR 0.33, 95% CI 0.23-0.46). CONCLUSION: Posterior HP is
      prevalent and associated with obesity, manual occupations, and physical
      inactivity. Prospective studies should assess the roles of obesity in causation
      and weight loss in treatment.

PMID- 25604331
TI  - Associations of psychological capital, demographic and occupational factors with
      cigarette smoking among Chinese underground coal miners.
AB  - BACKGROUND: As a specific male occupational group, underground coal miners have
      been commonly found to have a high prevalence of cigarette smoking. It is of
      urgent need to explore some factors that could be intervened to reduce smoking
      from personal or internal perspective. The purpose of the present study was to
      examine the associations of psychological capital (PsyCap), demographic and
      occupational factors with smoking among Chinese underground coal miners. METHODS:
      A cross-sectional survey was conducted in a coal-mining population in northeast
      China. Twenty-five hundreds of male underground miners were sampled from six coal
      mines. Self-administered questionnaires involving current smoking status,
      specific scales to measure the levels of PsyCap, effort-reward imbalance (ERI)
      and perceived physical environment (PPE), and some demographic and occupational
      factors were completed anonymously after a day shift. Complete responses were
      obtained from 1,956 participants (response rate: 78.2%). Multivariate logistic
      regression analysis was used to estimate the factors in relation to current
      smoking. RESULTS: The overall smoking prevalence was 52.4%. After controlling for
      demographic and occupational variables, PsyCap was not associated with smoking.
      Compared with the miners in the lowest tertile of resilience, the odds ratios
      (ORs) of smoking for the miners in the intermediate tertile and highest tertile
      were 1.30 (95% confidence intervals (CI): 0.99-1.70) and 1.58 (95% CI: 1.13
      2.20), respectively. Compared with the miners in the lowest tertile of optimism,
      the ORs of smoking for the miners in the intermediate tertile and highest tertile
      were 0.79 (95% CI: 0.61-1.03) and 0.69 (95% CI: 0.51-0.92), respectively. Low
      education and high PPE were the risk factors of smoking, whereas ERI had no
      association with smoking. CONCLUSIONS: More than half of the underground coal
      miners were current smokers, which indicated that cigarette smoking might be a
      common health risk behavior in this occupational population. High resilience and
      PPE, together with low education were the risk factors of smoking, whereas high
      optimism was a protective factor. Consequently, PsyCap had mixed effects on
      cigarette smoking. Investment in resilience and optimism should be given more
      attention for the purposes of the prevention and reduction of smoking among
      occupational populations.

PMID- 25604332
TI  - Drug development update.

PMID- 25604333
TI  - Optical monitoring of faradaic reaction using single plasmon-resonant nanorods
      functionalized with graphene.
AB  - Real-time optical monitoring of the electron-transfer process was achieved and
      modulated on individual gold nanoparticles functionalized with graphene. We found
      that charge accumulation on single gold nanorods (GNRs) depends on the rate of
      Faradaic reaction, which is synchronized with double-layer charging. 

PMID- 25604334
TI  - Hierarchically porous silicon-carbon-nitrogen hybrid materials towards highly
      efficient and selective adsorption of organic dyes.
AB  - The hierarchically macro/micro-porous silicon-carbon-nitrogen (Si-C-N) hybrid
      material was presented with novel functionalities of totally selective and highly
      efficient adsorption for organic dyes. The hybrid material was conveniently
      generated by the pyrolysis of commercial polysilazane precursors using
      polydivinylbenzene microspheres as sacrificial templates. Owing to the Van der
      Waals force between sp-hybridized carbon domains and triphenyl structure of dyes,
      and electrostatic interaction between dyes and Si-C-N matrix, it exhibites high
      adsorption capacity and good regeneration and recycling ability for the dyes with
      triphenyl structure, such as methyl blue (MB), acid fuchsin (AF), basic fuchsin
      and malachite green. The adsorption process is determined by both surface
      adsorption and intraparticle diffusion. According to the Langmuir model, the
      adsorption capacity is 1327.7 mg.g(-1) and 1084.5 mg.g(-1) for MB and AF,
      respectively, which is much higher than that of many other adsorbents. On the
      contrary, the hybrid materials do not adsorb the dyes with azo benzene
      structures, such as methyl orange, methyl red and congro red. Thus, the
      hierarchically porous Si-C-N hybrid material from a facile and low cost polymer
      derived strategy provides a new perspective and possesses a significant potential
      in the treatment of wastewater with complex organic pollutants. 

PMID- 25604335
TI  - Methanogenic archaea database containing physiological and biochemical
      characteristics.
AB  - The methanogenic archaea are a group of micro-organisms that have developed a
      unique metabolic pathway for obtaining energy. There are 150 characterized
      species in this group; however, novel species continue to be discovered. Since
      methanogens are considered a crucial part of the carbon cycle in the anaerobic
      ecosystem, characterization of these micro-organisms is important for
      understanding anaerobic ecology. A methanogens database (MDB;
      http://metanogen.biotech.uni.wroc.pl/), including physiological and biochemical
      characteristics of methanogens, was constructed based on the descriptions of
      isolated type strains. Analysis of the data revealed that methanogens are able to
      grow from 0 to 122  degrees C. Methanogens growing at the same temperature may
      have very different growth rates. There is no clear correlation between the
      optimal growth temperature and the DNA G+C content. The following substrate
      preferences are observed in the database: 74.5% of archaea species utilize
      H2+CO2, 33% utilize methyl compounds and 8.5% utilize acetate. Utilization of
      methyl compounds (mainly micro-organisms belonging to the genera Methanosarcina
      and Methanolobus ) is seldom accompanied by an ability to utilize H2+CO2. Very
      often, data for described species are incomplete, especially substrate
      preferences. Additional research leading to completion of missing information and
      development of standards, especially for substrate utilization, would be very
      helpful.

PMID- 25604336
TI  - Hyunsoonleella pacifica sp. nov., isolated from seawater of South Pacific Gyre.
AB  - A Gram-stain-negative, strictly aerobic, non-flagellated, non-gliding, oxidase-
      and catalase-positive and rod-shaped yellow-pigmented bacterium, designated
      strain SW033(T) was isolated from a surface seawater sample collected from the
      South Pacific Gyre (GPS position: 26 degrees  29' S 137 degrees  56' W) during
      the Integrated Ocean Drilling Program, expedition 329. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain SW033(T) belonged to the
      genus Hyunsoonleella and showed the highest 16S rRNA gene sequence similarity
      with Hyunsoonleella jejuensis CNU004(T) (96.8%). It showed 94.7-95.8% 16S rRNA
      gene sequence similarity with respect to members of the genera Jejuia ,
      Arenitalea and Algibacter in the family Flavobacteriaceae . Optimal growth
      occurred in the presence of 2-3% (w/v) NaCl, at pH 8.0 and at 28  degrees C. The
      genomic DNA G+C content of strain SW033(T) was 36.1 mol%. The major fatty acids
      were iso-C(15 : 1) G, iso-C(15 : 0), iso-C(17 : 0) 3-OH, iso-C(15 : 0) 3-OH and
      summed feature 3 (comprising C(16 : 1)omega7c and/or C(16 : 1)omega6c). The major
      respiratory quinone was menaquinone-6. The major polar lipids were
      phosphatidylethanolamine, two unidentified aminolipids and four unidentified
      lipids. On the basis of the polyphasic analyses, strain SW033(T) is considered to
      represent a member of a novel species in the genus Hyunsoonleella , for which the
      name Hyunsoonleella pacifica sp. nov. is proposed. The type strain is SW033(T) (
      = CGMCC 1.11009(T) = JCM 17860(T)).

PMID- 25604337
TI  - Cetia pacifica gen. nov., sp. nov., a chemolithoautotrophic, thermophilic,
      nitrate-ammonifying bacterium from a deep-sea hydrothermal vent.
AB  - A thermophilic, anaerobic, chemolithoautotrophic bacterium, strain TB-6(T), was
      isolated from a deep-sea hydrothermal vent located on the East Pacific Rise at 9
      degrees  N. The cells were Gram-staining-negative and rod-shaped with one or more
      polar flagella. Cell size was approximately 1-1.5 um in length and 0.5 um in
      width. Strain TB-6(T) grew between 45 and 70  degrees C (optimum 55-60  degrees
      C), 0 and 35 g NaCl l(-1) (optimum 20-30 g l(-1)) and pH 4.5 and 7.5 (optimum pH
      5.5-6.0). Generation time under optimal conditions was 2 h. Growth of strain TB
      6(T) occurred with H2 as the energy source, CO2 as the carbon source and nitrate
      or sulfur as electron acceptors, with formation of ammonium or hydrogen sulfide,
      respectively. Acetate, (+)-d-glucose, Casamino acids, sucrose and yeast extract
      were not used as carbon and energy sources. Inhibition of growth occurred in the
      presence of lactate, peptone and tryptone under a H2/CO2 (80 : 20; 200 kPa) gas
      phase. Thiosulfate, sulfite, arsenate, selenate and oxygen were not used as
      electron acceptors. The G+C content of the genomic DNA was 36.8 mol%.
      Phylogenetic analysis of the 16S rRNA gene of strain TB-6(T) showed that this
      organism branched separately from the three most closely related genera,
      Caminibacter , Nautilia and Lebetimonas , within the family Nautiliaceae . Strain
      TB-6(T) contained several unique fatty acids in comparison with other members of
      the family Nautiliaceae . Based on experimental evidence, it is proposed that the
      organism represents a novel species and genus within the family Nautiliaceae ,
      Cetia pacifica, gen. nov., sp. nov. The type strain is TB-6(T) ( = DSM 27783(T) =
      JCM 19563(T)). 

PMID- 25604338
TI  - Serinibacter tropicus sp. nov., an actinobacterium isolated from the rhizosphere
      of a mangrove, and emended description of the genus Serinibacter.
AB  - A novel Gram-stain-positive actinobacterium, designated PS-14-7(T), was isolated
      from the rhizosphere of a mangrove on Pramuka Island, Indonesia, and its
      taxonomic position was investigated using a polyphasic approach. The
      peptidoglycan type of strain PS-14-7(T) was A4alpha and lysine was the diagnostic
      diamino acid of the peptidoglycan. The predominant menaquinone was MK-8(H4) and
      the major fatty acids were anteiso-C(15 : 0), C(16 : 0) and iso-C(16 : 0). The
      DNA G+C content was 72.8 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequence comparisons revealed that strain PS-14-7(T) was closely related to
      Serinibacter salmoneus Kis4-28(T) (99.6%). However, DNA-DNA hybridization and
      phenotypic characteristics revealed that strain PS-14-7(T) differed from
      Serinibacter salmoneus . Therefore, strain PS-14-7(T) represents a novel species
      of the genus Serinibacter , for which the name Serinibacter tropicus sp. nov. is
      proposed. The type strain is PS-14-7(T) ( = NBRC 110108(T) = InaCC A 515(T)). An
      emended description of the genus Serinibacter is also proposed.

PMID- 25604339
TI  - Dyadobacter jiangsuensis sp. nov., a methyl red degrading bacterium isolated from
      a dye-manufacturing factory.
AB  - A Gram-stain-negative, non-motile, rod-shaped bacterial strain, L-1(T), which was
      capable of degrading methyl red was isolated from a dye-manufacturing factory in
      China. Phenotypic, chemotaxonomic and phylogenetic analyses established
      affiliation of the isolate to the genus Dyadobacter . Cells occurred in pairs in
      young cultures but became chains of coccoid cells in old cultures, and produced a
      flexirubin-like yellow pigment. Strain L-1(T) could not hydrolyse cellulose, and
      had a DNA G+C content of 51.3 mol%. The major cellular fatty acids were iso-C(15
      : 0), C(16 : 1)omega5c, iso-C(17 : 0) 3-OH and summed feature 3 (C(16 : 1)omega7c
      and/or C(16 : 1)omega6c). C(16 : 0), iso-C(15 : 0) 3-OH and C(16 : 0) 3-OH were
      the other major fatty acid components. Comparative 16S rRNA gene sequence
      analysis showed that strainL-1(T) was most closely related to Dyadobacter
      fermentans DSM 18053(T) (99.2%), Dyadobacter soli JCM 16232(T) (98.9%) and
      Dyadobacter beijingensis CGMCC 1.6375(T) (98.7%). However, the new isolate
      exhibited relatively low levels of DNA-DNA relatedness with respect to JCM
      16232(T) (41.2+/-1.8%), DSM 18053(T) (38.6+/-2.6%) and CGMCC 1.6375(T) (35.0+/
      2.1%). Strain L-1(T) could also be differentiated from its closest phylogenetic
      relatives based on differences in several phenotypic characteristics. These data
      suggest that strain L-1(T) represents a novel species of the genus Dyadobacter ,
      for which the name Dyadobacter jiangsuensis sp. is proposed. The type strain is L
      1(T) (DSM 29057(T) = CGMCC 1.12969(T)).

PMID- 25604340
TI  - Methanosarcina subterranea sp. nov., a methanogenic archaeon isolated from a deep
      subsurface diatomaceous shale formation.
AB  - A methanogenic archaeon, strain HC-2(T), was isolated from a deep diatomaceous
      shale formation. The strain grew on methanol, monomethylamine, dimethylamine,
      trimethylamine and dimethylsulphide, but not on acetate, H2/CO2, formate, 2
      propanol, 2-butanol or cyclopentanol. Cells were Gram-stain-negative, non-motile,
      and coccus-like, 0.9-1.4 um in diameter, and occurred singly, in pairs, or as
      aggregates. The strain grew at 10-40  degrees C (optimum 35  degrees C), pH 5.9
      7.4 (optimum pH 6.6-6.8) and in 0-0.6 M NaCl (optimum 0.1-0.2 M). The genomic DNA
      G+C content was 41.5 mol% and the 16S rRNA gene sequence was closely related to
      those of Methanosarcina lacustris DSM 13486(T) (99.1%) and Methanosarcina
      siciliae DSM 3028(T) (98.3%). Values for DNA-DNA hybridization with these strains
      were less than 30%. The phenotypic and phylogenetic features of HC-2(T) indicate
      that it represents a novel species of the genus Methanosarcina , for which the
      name Methanosarcina subterranea sp. nov. is proposed. The type strain is HC-2(T)
      ( = DSM 22503(T) = JCM 15540(T) = NBRC 102578(T)).

PMID- 25604341
TI  - Comparison of potential diatom 'barcode' genes (the 18S rRNA gene and ITS, COI,
      rbcL) and their effectiveness in discriminating and determining species taxonomy
      in the Bacillariophyta.
AB  - Diatoms form an enormous group of photoautotrophic micro-eukaryotes and play a
      crucial role in marine ecology. In this study, we evaluated typical genes to
      determine whether they were effective at different levels of diatom clustering
      analysis to assess the potential of these regions for barcoding taxa. Our test
      genes included nuclear rRNA genes (the nuclear small-subunit rRNA gene and the
      5.8S rRNA gene+ITS-2), a mitochondrial gene (cytochrome c-oxidase subunit 1,
      COI), a chloroplast gene [ribulose-1,5-biphosphate carboxylase/oxygenase large
      subunit (rbcL)] and the universal plastid amplicon (UPA). Calculated genetic
      divergence was highest for the internal transcribed spacer (ITS; 5.8S+ITS-2) (p
      distance of 1.569, 85.84% parsimony-informative sites) and COI (6.084, 82.14%),
      followed by the 18S rRNA gene (0.139, 57.69%), rbcL (0.120, 42.01%) and UPA
      (0.050, 14.97%), which indicated that ITS and COI were highly divergent compared
      with the other tested genes, and that their nucleotide compositions were variable
      within the whole group of diatoms. Bayesian inference (BI) analysis showed that
      the phylogenetic trees generated from each gene clustered diatoms at different
      phylogenetic levels. The 18S rRNA gene was better than the other genes in
      clustering higher diatom taxa, and both the 18S rRNA gene and rbcL performed well
      in clustering some lower taxa. The COI region was able to barcode species of some
      genera within the Bacillariophyceae. ITS was a potential marker for DNA based
      taxonomy and DNA barcoding of Thalassiosirales, while species of Cyclotella,
      Skeletonema and Stephanodiscus gathered in separate clades, and were paraphyletic
      with those of Thalassiosira. Finally, UPA was too conserved to serve as a diatom
      barcode.

PMID- 25604342
TI  - Ichthyenterobacterium magnum gen. nov., sp. nov., a member of the family
      Flavobacteriaceae isolated from olive flounder (Paralichthys olivaceus).
AB  - A novel marine bacterium isolated from the intestine of cultured flounder
      (Paralichthys olivaceus) was studied by using a polyphasic taxonomic approach.
      The isolate was Gram-stain-negative, pleomorphic, aerobic, yellow and oxidase-
      and catalase-negative. Phylogenetic analysis of 16S rRNA gene sequences indicated
      that isolate Th6(T) formed a distinct branch within the family Flavobacteriaceae
      and showed 96.6% similarity to its closest relative, Bizionia hallyeonensis T
      y7(T). The DNA G+C content was 29 mol%. The major respiratory quinone was MK-6.
      The predominant fatty acids were iso-C(15 : 1) G, iso-C(15 : 0), iso-C(15 : 0) 3
      OH, iso-C(17 : 0) 3-OH and summed feature 3 (C(15 : 1)omega6c and/or C(16 :
      1)omega7c). On the basis of the phenotypic, chemotaxonomic and phylogenetic
      characteristics, the novel bacterium has been assigned to a novel species of a
      new genus for which the name Ichthyenterobacterium magnum gen. nov., sp. nov. is
      proposed. The type strain is Th6(T) ( = JCM 18636(T) = KCTC 32140(T)).

PMID- 25604343
TI  - Melghiribacillus thermohalophilus gen. nov., sp. nov., a novel filamentous,
      endospore-forming, thermophilic and halophilic bacterium.
AB  - A novel filamentous, endospore-forming, thermophilic and moderately halophilic
      bacterium designated strain Nari2A(T) was isolated from soil collected from an
      Algerian salt lake, Chott Melghir. The novel isolate was Gram-staining-positive,
      aerobic, catalase-negative and oxidase-positive. Optimum growth occurred at 50-55
      degrees C, 7-10% (w/v) NaCl and pH 7-8. The strain exhibited 95.4, 95.4 and
      95.2% 16S rRNA gene sequence similarity to Thalassobacillus devorans G19.1(T),
      Sediminibacillus halophilus EN8d(T) and Virgibacillus kekensis YIM-kkny16(T),
      respectively. The major menaquinone was MK-7. The polar lipid profile consisted
      of phosphatidylglycerol, diphosphatidylglycerol, three unknown phosphoglycolipids
      and two unknown phospholipids. The predominant cellular fatty acids were iso-C(15
      : 0) and iso-C(17 : 0). The DNA G+C content was 41.9 mol%. Based on the
      phenotypic, chemotaxonomic and phylogenetic data, strain Nari2A(T) is considered
      to represent a novel species of a new genus in the family Bacillaceae , order
      Bacillales , for which the name Melghiribacillus thermohalophilus gen. nov., sp.
      nov. is proposed. The type strain of Melghiribacillus thermohalophilus is
      Nari2A(T) ( = DSM 25894(T) = CCUG 62543(T)).

PMID- 25604344
TI  - Rhodanobacter koreensis sp. nov., a bacterium isolated from tomato rhizosphere.
AB  - A Gram-stain-negative, aerobic, rod-shaped and motile bacterium, designated THG
      DD7(T), was isolated from tomato plant rhizosphere soil. Strain THG-DD7(T) grew
      optimally at 25-30  degrees C, at pH 7.0-7.5 and in the presence of 0.5% (w/v)
      NaCl. According to the results of 16S rRNA gene sequence comparisons, strain THG
      DD7(T) was most closely related to Rhodanobacter umsongensis GR24-2(T) (98.2%),
      Rhodanobacter panaciterrae LnR5-47(T) (98.0%), Rhodanobacter soli DCY45(T)
      (97.9%), Rhodanobacter terrae GP18-1(T) (97.9%) and Dyella ginsengisoli Gsoil
      3046(T) (97.7%). The DNA G+C content was 65.2 mol%. In DNA-DNA hybridization, the
      DNA relatedness levels between strain THG-DD7(T) and its closest phylogenetically
      neighbours were below 40.0%. The predominant isoprenoid quinone was ubiquinone Q
      8. The major polar lipids were diphosphatidylglycerol, phosphtidylethanolamine,
      phosphatidyl-N-methylethanolamine and phosphatidylglycerol. The major fatty acids
      were iso-C(15 : 0), iso-C(16 : 0), iso-C(17 : 0), anteiso-C(15 : 0) and iso-C(17
      : 1)omega9c and/or C(16 : 0) 10-methyl (summed feature 9). These data supported
      the affiliation of strain THG-DD7(T) to the genus Rhodanobacter . The results of
      physiological and biochemical tests enabled strain THG-DD7(T) to be
      differentiated genotypically and phenotypically from the species of the genus
      Rhodanobacter with validly published names. Therefore, the novel isolate
      represents a novel species, for which the name Rhodanobacter koreensis sp. nov.
      is proposed. The type strain is THG-DD7(T) ( = KACC 17650(T) = JCM 19614(T)).

PMID- 25604345
TI  - Sphingomonas gei sp. nov., isolated from roots of Geum aleppicum.
AB  - A yellow-pigmented bacterium, designated strain ZFGT-11(T), was isolated from
      roots of Geum aleppicum Jacq. collected from Taibai Mountain in Shaanxi Province,
      north-west China, and was subjected to a taxonomic study by using a polyphasic
      approach. Cells of strain ZFGT-11(T) were Gram-stain-negative, strictly aerobic
      rods that were surrounded by a thick capsule and were motile by means of a single
      polar flagellum. Phylogenetic analyses based on 16S rRNA gene sequences showed
      that strain ZFGT-11(T) was a member of the genus Sphingomonas and was closely
      related to Sphingomonas naasensis KACC 16534(T) (97.6% similarity), Sphingomonas
      kyeonggiense JCM 18825(T) (96.8%), Sphingomonas asaccharolytica IFO 15499(T)
      (96.7%) and Sphingomonas leidyi DSM 4733(T) (96.6%). The predominant respiratory
      quinone was ubiquinone-10 (Q-10) and the major cellular fatty acids were summed
      feature 8 (comprising C(18 : 1)omega7c and/or C(18 : 1)omega6c), C(17 :
      1)omega6c, C(14 : 0) 2-OH, C(16 : 0) and C(15 : 0) 2-OH. The major polyamine of
      strain ZFGT-11(T) was sym-homospermidine. Phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmonomethylethanolamine, phosphatidylcholine, sphingoglycolipid, two
      unidentified aminoglycolipids, two unidentified phospholipids and two
      unidentified lipids were detected in the polar lipid profile. The DNA G+C content
      was 66.8 mol%. DNA-DNA relatedness for strain ZFGT-11(T) with respect to its
      closest phylogenetic relative S. naasensis KACC 16534(T) was 26.2+/-4.8% (mean+/
      SD). On the basis of data from the present polyphasic taxonomic study, strain
      ZFGT-11(T) is considered to represent a novel species of the genus Sphingomonas ,
      for which the name Sphingomonas gei sp. nov. is proposed. The type strain is ZFGT
      11(T) ( = CCTCC AB 2013306(T) = KCTC 32449(T) = LMG 27608(T)).

PMID- 25604346
TI  - Acute protease supplementation effects on muscle damage and recovery across
      consecutive days of cycle racing.
AB  - Bromelain, a mixture of proteases obtained from pineapples, has been demonstrated
      to reduce exercise-induced muscle damage and inflammation, enhancing recovery.
      This investigation aimed to establish if markers of muscle damage and
      testosterone were influenced by acute bromelain supplementation in competitive
      cyclists taking part in a six-day cycle stage race. Fifteen highly trained
      cyclists [age: 22, [Formula: see text] = 1.2 years, height: 1.79, [Formula: see
      text] = 0.01 m, body mass: 68.69, [Formula: see text] = 1.97 kg] were
      supplemented with either bromelain (1000 mg.day(-1)) (n = 8) or a placebo (n = 7)
      across six days of competitive racing in a randomised, double-blind, placebo
      controlled trial. Blood was collected from each cyclist on days one, three and
      six of racing and analysed for creatine kinase (CK), myoglobin, lactate
      dehydrogenase (LDH) and testosterone. CK activity (P < 0.001, d = 17.4-18.8), LDH
      activity (P < 0.004, d = 0.5-2.5) and myoglobin concentration (P < 0.007, d = 3.4
      4.8) were elevated from pre-race on days three and six of racing in both groups.
      Testosterone concentrations were significantly lower on the final day of racing
      (P = 0.03, d = 1.3) and there was a trend for bromelain to maintain testosterone
      concentrations across the race period (P = 0.05, d = 1.04-1.70) when compared to
      placebo. Fatigue rating was lower in the bromelain group on day four of racing (P
      = 0.01). Consecutive days of competitive cycling were associated with increased
      markers of muscle damage and a reduction in circulating testosterone across the
      race period. Bromelain supplementation reduced subjective feelings of fatigue and
      was associated with a trend to maintain testosterone concentration. 

PMID- 25604347
TI  - Stable heterocyclopentane-1,3-diyls.
AB  - Diphosphadiazanediyl, [(MU-NR)P]2 (R=Ter=2,6-dimesitylphenyl), is known to
      readily activate small molecules with multiple bonds. CO is an especially
      intriguing species for activation, because either 1,1- or 1,2-bridging mode would
      lead to a [1.1.1]bicycle or a carbene, respectively. The activation of CO with
      diphosphadiazanediyl already occurs at ambient temperatures (1 bar, 25  degrees
      C). However, CO is involved in an unprecedented ring expansion reaction under
      preservation of the biradical character, which leads to the formation of the
      first stable cyclopentane-1,3-diyl analogue displaying photochromic molecular
      switch characteristics. 

PMID- 25604348
TI  - Assessment of elevated pentraxin 3 levels in systemic sclerosis: comment on the
      article by Shirai et al.

PMID- 25604349
TI  - Ontogeny of septohippocampal modulation of delay eyeblink conditioning.
AB  - The current study investigated the effects of disrupting the septohippocampal
      theta system on the developmental emergence of delay eyeblink conditioning. Theta
      oscillations are defined as electroencephalographic (EEG) waveforms with a
      frequency between 3-8 Hz. Hippocampal theta oscillations are generated by inputs
      from the entorhinal cortex and the medial septum. Theta activity has been shown
      to facilitate learning in a variety of paradigms, including delay eyeblink
      conditioning. Lesions of the medial septum disrupt theta activity and slow the
      rate at which delay eyeblink conditioning is learned (Berry & Thompson, [1979]
      Science 200:1298-1300). The role of the septohippocampal theta system in the
      ontogeny of eyeblink conditioning has not been examined. In the current study,
      infant rats received an electrolytic lesion of the medial septum on postnatal day
      (P) 12. Rats were later given eyeblink conditioning for 6 sessions with an
      auditory conditioned stimulus on P17-19, P21-23, or P24-26. Lesions impaired
      eyeblink conditioning on P21-23 and P24-26 but not on P17-19. The results suggest
      that the septohippocampal system comes online to facilitate acquisition of
      eyeblink conditioning between P19 and P21. Developmental changes in
      septohippocampal modulation of the cerebellum may play a significant role in the
      ontogeny of eyeblink conditioning.

PMID- 25604350
TI  - Follicular variant of peripheral T cell lymphoma with mediastinal involvement in
      a child: a case report.
AB  - Peripheral T cell lymphomas are rare in young patients. We report the first case
      of a follicular variant of peripheral T cell lymphoma not otherwise specified in
      an 11-year-old boy, who presented with a large mediastinal mass. Microscopic
      examination of the mediastinal biopsy revealed nodular infiltration of medium- to
      large-sized atypical lymphocytes. Immunohistochemistry showed expression of
      follicular helper T cell markers (CD10, PD1, CXCL13, and BCL6) in tumor T cells.
      Epstein-Barr virus (EBV) was not detected by an in situ hybridization assay for
      EBV-encoded RNA. Interestingly, fluorescence in situ hybridization detected the
      presence in the tumor cells of the t(5;9)(q33;q22) translocation, involving ITK
      and SYK rearrangement. T cell clonality was detected by multiplex PCR analysis of
      TRG and TRD gene rearrangements. After 4 cycles of systemic chemotherapy, the
      patient was in complete remission. Although this entity is very rare, our
      observations show that lymphomas arising from T follicular helper cells may occur
      in children and that this should be distinguished from other lymphomas, such T
      lymphoblastic lymphomas, which require a specific therapeutic approach.

PMID- 25604352
TI  - Five-step authorship framework to improve transparency in disclosing contributors
      to industry-sponsored clinical trial publications.
AB  - Authorship guidelines have established criteria to guide author selection based
      on significance of contribution and helped to define associated responsibilities
      and accountabilities for the published findings. However, low awareness, variable
      interpretation, and inconsistent application of these guidelines can lead to
      confusion and a lack of transparency when recognizing those who merit authorship.
      This article describes a research project led by the Medical Publishing Insights
      and Practices (MPIP) Initiative to identify current challenges when determining
      authorship for industry-sponsored clinical trials and develop an improved
      approach to facilitate decision-making when recognizing authors from related
      publications. A total of 498 clinical investigators, journal editors, publication
      professionals and medical writers were surveyed to understand better how they
      would adjudicate challenging, real-world authorship case scenarios, determine the
      perceived frequency of each scenario and rate their confidence in the responses
      provided. Multiple rounds of discussions about these results with journal
      editors, clinical investigators and industry representatives led to the
      development of key recommendations intended to enhance transparency when
      determining authorship. These included forming a representative group to
      establish authorship criteria early in a trial, having all trial contributors
      agree to these criteria and documenting trial contributions to objectively
      determine who warrants an invitation to participate in the manuscript development
      process. The resulting Five-step Authorship Framework is designed to create a
      more standardized approach when determining authorship for clinical trial
      publications. Overall, these recommendations aim to facilitate more transparent
      authorship decisions and help readers better assess the credibility of results
      and perspectives of the authors for medical research more broadly. Please see
      related article: http://www.biomedcentral.com/1741-7015/12/214.

PMID- 25604351
TI  - Identification and characterization of microRNAs from Chinese pollination
      constant non-astringent persimmon using high-throughput sequencing.
AB  - BACKGROUND: microRNAs (miRNAs) have been shown to play key roles in regulating
      gene expression at post-transcriptional level, but miRNAs associated with natural
      deastringency of Chinese pollination-constant nonastringent persimmon (CPCNA)
      have never been identified. RESULTS: In this study, two small RNA libraries
      established using 'Eshi No. 1' persimmon (Diospyros kaki Thunb.; CPCNA) fruits
      collected at 15 and 20 weeks after flowering (WAF) were sequenced through Solexa
      platform in order to identify miRNAs involved in deastringency of persimmon. A
      total of 6,258,487 and 7,634,169 reads were generated for the libraries at 15 and
      20 WAF, respectively. Based on sequence similarity and hairpin structure
      prediction, 236 known miRNAs belonging to 65 miRNA families and 33 novel miRNAs
      were identified using persimmon transcriptome data. Sixty one of the
      characterized miRNAs exhibited pronounced difference in the expression levels
      between 15 and 20 WAF, 17 up-regulated and 44 down-regulated. Expression profiles
      of 12 conserved and 10 novel miRNAs were validated by stem loop qRT-PCR. A total
      of 198 target genes were predicted for the differentially expressed miRNAs,
      including several genes that have been reported to be implicated in
      proanthocyanidins (PAs, or called tannin) accumulation. In addition, two
      transcription factors, a GRF and a bHLH, were experimentally confirmed as the
      targets of dka-miR396 and dka-miR395, respectively. CONCLUSIONS: Taken together,
      the present data unraveled several important miRNAs in persimmon. Among them,
      miR395p-3p and miR858b may regulate bHLH and MYB, respectively, which are
      influenced by SPL under the control of miR156j-5p and in turn regulate the
      structural genes involved in PA biosynthesis. In addition, dka-miR396g and
      miR2911a may regulate their target genes associated with glucosylation and
      insolubilization of tannin precursors. All of these miRNAs might play key roles
      in the regulation of (de)astringency in persimmon fruits under normal development
      conditions.

PMID- 25604354
TI  - Synthesis of 7-alkylidene-7,12-dihydroindolo[3,2-d]benzazepine-6-(5H)-ones (7
      alkylidene-paullones) by N-cyclization-oxidative Heck cascade and
      characterization as sirtuin modulators.
AB  - An extension of our reported protocol to benzofused heterocyclic derivatives
      (benzofurans, indoles, isochromeneimines), involving a palladium-induced cascade
      of N-cyclization and oxidative Heck reactions of o-alkynylanilines, has allowed
      the preparation of indolobenzazepinones (paullones) with an alkylidene group at
      C7 in just 3-4 steps from ortho-iodoanilines. Some of these compounds behave as
      Sirt1 activators in biochemical assays. 

PMID- 25604353
TI  - Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles
      (Lipomer) using Box Behnken design.
AB  - BACKGROUND: The objective of the study was to formulate and to investigate the
      combined influence of 3 independent variables in the optimization of Polymeric
      lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal
      drug Itraconazole and to improve intestinal permeability. METHOD: The Polymeric
      lipid hybrid nanoparticle formulation was prepared by the emulsification solvent
      evaporation method and 3 factor 3 level Box Behnken statistical design was used
      to optimize and derive a second order polynomial equation and construct contour
      plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and
      Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected
      were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration
      of the drug (X3). RESULT: The Box-Behnken design demonstrated the role of the
      derived equation and contour plots in predicting the values of dependent
      variables for the preparation and optimization of Itraconazole PLHNs.
      Itraconazole PLHNs revealed nano size (210 +/- 1.8 nm) with an entrapment
      efficiency of 83 +/- 0.6% and negative zeta potential of -11.7 mV and also
      enhance the permeability of itraconazole as the permeability coefficient (Papp)
      and the absorption enhancement ratio was higher. CONCLUSION: The tunable particle
      size, surface charge, and favourable encapsulation efficiency with a sustained
      drug release profile of PLHNs suggesting that it could be promising system
      envisioned to increase the bioavailability by improving intestinal permeability
      through lymphatic uptake, M cell of payer's patch or paracellular pathway which
      was proven by confocal microscopy.

PMID- 25604355
TI  - Treatment of hepatitis C in liver transplant patients: interferon out, direct
      antiviral combos in.
AB  - Although chronic infection with hepatitis C virus (HCV) is the leading indication
      for liver transplantation in the United States, graft and patient survival rates
      are reduced because of HCV recurrence after transplant. Interferon-based
      antiviral treatment administered either before or after transplant to prevent or
      treat HCV recurrence, respectively, is limited because of poor tolerability and
      low efficacy. However, the treatment of HCV in the transplant setting is changing
      considerably with the availability of newer direct-acting antivirals and
      interferon-free regimens. This article will review the experience to date with
      treating HCV in the setting of cirrhosis and liver transplantation and will
      discuss the unique challenges encountered when this population is being treated.

PMID- 25604356
TI  - Modulation of electronic and redox properties in phenolate-rich cobalt(III)
      complexes and their implications for catalytic proton reduction.
AB  - We investigate the redox, spectroscopy and catalytic reactivity of new
      cobalt(iii) complexes based on phenolate-rich [N2O3] ligands. These complexes are
      described as [Co(III)(L(X))MeOH], where X indicates the presence of chloro (),
      bromo (), iodo (), or tert-butyl () substituents in the 3(rd) and 5(th) positions
      of each phenolate ring. These substituents modulate the Co(iii) <- PheO(-) LMCT
      bands of the parent complexes with (451) > (453) > (456) > (468 nm) and the redox
      potentials involved with the Co(iii)/Co(ii) and ligand reduction and with the
      phenolate/phenoxyl oxidation processes. The influence of the substituents on the
      phenolate pendant arms was also observed on the kinetic parameters; presented a
      rate constant of 1.0 * 10(-3) s(-1) whereas showed a considerably slower rate
      (5.3 * 10(-5) s(-1)). Species and are electrocatalysts towards proton reduction
      in the presence of weak acid in acetonitrile. A TON of 10.8 was observed for
      after 3 h of bulk electrolysis at -2.20 VFc/Fc(+) using a mercury pool as the
      working electrode. 

PMID- 25604357
TI  - Assignment of homoeologs to parental genomes in allopolyploids for species tree
      inference, with an example from Fumaria (papaveraceae).
AB  - There is a rising awareness that species trees are best inferred from multiple
      loci while taking into account processes affecting individual gene trees, such as
      substitution model error (failure of the model to account for the complexity of
      the data) and coalescent stochasticity (presence of incomplete lineage sorting
      [ILS]). Although most studies have been carried out in the context of dichotomous
      species trees, these processes operate also in more complex evolutionary
      histories involving multiple hybridizations and polyploidy. Recently, methods
      have been developed that accurately handle ILS in allopolyploids, but they are
      thus far restricted to networks of diploids and tetraploids. We propose a
      procedure that improves on this limitation by designing a workflow that assigns
      homoeologs to hypothetical diploid ancestral genomes prior to genome tree
      construction. Conflicting assignment hypotheses are evaluated against
      substitution model error and coalescent stochasticity. Incongruence that cannot
      be explained by stochastic mechanisms needs to be explained by other processes
      (e.g., homoploid hybridization or paralogy). The data can then be filtered to
      build multilabeled genome phylogenies using inference methods that can recover
      species trees, either in the face of substitution model error and coalescent
      stochasticity alone, or while simultaneously accounting for hybridization.
      Methods are already available for folding the resulting multilabeled genome
      phylogeny into a network. We apply the workflow to the reconstruction of the
      reticulate phylogeny of the plant genus Fumaria (Papaveraceae) with ploidal
      levels ranging from 2[Formula: see text] to 14[Formula: see text]. We describe
      the challenges in recovering nuclear NRPB2 homoeologs in high ploidy species
      while combining in vivo cloning and direct sequencing techniques. Using
      parametric bootstrapping simulations we assign nuclear homoeologs and chloroplast
      sequences (four concatenated loci) to their common hypothetical diploid ancestral
      genomes. As these assignments hinge on effective population size assumptions, we
      investigate how varying these assumptions impacts the recovered multilabeled
      genome phylogeny. 

PMID- 25604358
TI  - Silver Jubilee of JCPSP: a story of successes and achievements.

PMID- 25604359
TI  - Fortifying the external peer review: an editorial perspective.

PMID- 25604360
TI  - The developmental gross morphology of pancreas in chick embryo after prenatal
      administration of valproic acid.
AB  - OBJECTIVE: To determine the effects of prenatal administration of valproic acid
      on the developmental gross morphology of pancreas in chick embryo. STUDY DESIGN:
      Experimental study. PLACE AND DURATION OF STUDY: Anatomy Department, Regional
      Centre, College of Physicians and Surgeons, Islamabad, from February 2010 to
      February 2011. METHODOLOGY: An experimental group-A and control group-B,
      comprised of 30 eggs each. Freshly laid fertilized chicken eggs of experimental
      group were injected with valproic acid, incubated and hatched. Eggs of control
      group underwent sham treatment using normal saline. The chicks were sacrificed on
      hatching or day 22 of incubation, whichever was earlier. The pancreata of only
      alive chicks of both groups were dissected out, and evaluated for gross
      morphology in terms of length and weight by statistically comparing with control
      ones. Then pancreata were stained with aldehyde fuchsin and orange-G stain to
      study other obvious histological effects, if any. RESULTS: Chicken embryos
      exposed to valproic acid in ovo, showed significant decrease in length and weight
      of pancreata. The mean of length (cm) of pancreata in group-A was 2.208 +/-
      0.166, and group-B was 2.300 +/- 0.102 (p=0.008). The mean of weight (g) of
      pancreata in group-A was 0.032 +/- 0.009, and group-B was 0.048 +/- 0.005
      (p=0.001). CONCLUSION: Valproic acid exposure showed retarding effect on the
      gross development of pancreas as depicted by decrease in the length and weight of
      pancreata.

PMID- 25604362
TI  - Utility of Brain Natriuretic Peptide in diagnosis of congestive heart failure and
      comparison with trans-thoracic echocardiography: a multicenter analysis in South
      Asian and Arabian population.
AB  - OBJECTIVE: To evaluate serum Brain Natriuretic Peptide levels (BNP) as a
      screening test in the diagnosis of congestive heart failure. STUDY DESIGN:
      Comparative cross-sectional study. PLACE AND DURATION OF STUDY: Prince Salman
      Heart Center, King Fahad Medical City, Riyadh, Saudi Arabia between December 2010
      to January 2012 and Nishtar Hospital, Multan, Pakistan, from February to August
      2006. METHODOLOGY: A total of 80 patients with clinical diagnosis of Congestive
      Heart Failure (CHF) underwent measurement of serum BNP and had a trans-thoracic
      echocardiography to measure Ejection Fraction (EF). The normal limit for serum
      BNP levels, provided by the manufacturer of the kit was applied as a cut-off
      value for BNP. EF of > 45% was considered normal. RESULTS: Forty seven patients
      (94%) had an EF < 45%. BNP levels were elevated in 36 patients (72%). Sensitivity
      and specificity of BNP was found to be 80% and 66% respectively and accuracy was
      80%. CONCLUSION: BNP measurements as a screening tool for CHF has good
      sensitivity and accuracy when compared to echocardiography.

PMID- 25604361
TI  - Endovascular treatment of renal artery stenoses.
AB  - OBJECTIVE: To evaluate the procedure success and effect on hypertension after
      stenting of incidentally diagnosed atherosclerotic renal artery stenoses. STUDY
      DESIGN: An experimental study. PLACE AND DURATION OF STUDY: A multicentric study
      was conducted at the Plastic Surgery and General Hospital, National Medical
      Center and Ziauddin University Hospital, Karachi, Pakistan from January 2009 to
      March 2013. METHODOLOGY: Hypertension (systolic blood pressure > 160 and
      diastolic > 90 mmHg with two or more than two medications) with coronary artery
      disease were initially evaluated for coronary angiography, Renal artery
      angiography was also endovascular performed and stent was deployed for
      atherosclerotic renal artery stenosis when found. Blood pressure readings,
      reduction in need of antihypertensive medication and serum creatinine levels were
      taken as outcome measures. Patients having renal artery stenoses secondary to
      connective tissue disorders and fibromuscular dysplasia were excluded. RESULTS:
      There were 25 patients, 14 (56%) male and 11 (44%) female, with mean age of 49 +/
      6 years. Diabetes mellitus, dyslipidemia and smoking were seen in 11 (44%), 10
      (40%) and 4 (16%) patients respectively. Renal insufficiency (serum creatinine >
      1.5 mg/dl) was seen in one (04%) patient. Bilateral, and isolated right and left
      renal artery stenoses was seen in 5 (20%), 9 (36%) and 11(44%) patients
      respectively. Mean percentage of renal artery stenoses was 89%, ranged from 70%
      to 99% while ostial lesion was found in 20 (80%) patients. A significant decrease
      in systolic (168.20 +/- 9.987 vs. 140.60 +/- 5.649 mmHg, p < 0.001) and diastolic
      blood pressure (88.60 +/- 5.50 vs. 77.20 +/- 5.017 mmHg, p < 0.001) and reduction
      of medication (2.72 +/- 0.458 vs. 1.5 +/- 0.510, p < 0.01) were noted without a
      change in renal function (p= 0.061) after renal artery stenting. CONCLUSION:
      Endovascular stenting of renal artery stenoses in patients with poorly controlled
      hypertension is a safe and effective treatment.

PMID- 25604363
TI  - Balloon valvuloplasty in dysplastic pulmonary valve stenosis: immediate and
      intermediate outcomes.
AB  - OBJECTIVE: To determine the immediate and intermediate outcome in dysplastic and
      doming pulmonary valve stenosis in children and to determine various factors
      associated with unsuccessful outcome. STUDY DESIGN: An interventional study.
      PLACE AND DURATION OF STUDY: The Children's Hospital, Lahore, Pakistan, from June
      2006 to December 2012. METHODOLOGY: All patients presenting with severe pulmonary
      valve stenosis were enrolled in the study. Balloon valvuloplasty was performed on
      all patients. Successful outcome (residual gradient < 36 mmHg) was compared with
      matched doming pulmonary valve stenosis control group valvuloplasty. Difference
      in various quantitative variables was calculated using independent t-test and
      Mann Whitney U test. Categorical variables were compared using Chi square and
      Kruskal-Wallis test. Multivariate analysis was performed to determine various
      factors associated with outcome. Kaplan- Meier survival table was used to
      determine freedom from re-intervention proportions. RESULTS: One hundred and
      fifty two patients (Dysplastic group A, n=73; Doming group B, n=79) with median
      age of 24 months (range 3 - 192 months) and M:F; 2:1 were included in the study.
      Mean gradient decreased from 96 +/- 33 mmHg to 29 +/- 20 mmHg. Group A had
      significantly higher number of patients with unsuccessful outcome (9.6%, p=0.02).
      Preprocedure gradient > 75 mmHg was the most significant factor associated with
      unsuccessful outcome (p < 0.001). Median follow-up duration was 3 years (range 1 
      6 years). Freedom from re-intervention proportion at 1, 3 and 6 years was 91.3%,
      86.7% and 78.9% respectively in group A compared to 100%, 96.5% and 96.5%
      respectively in group B. Immediate postprocedure gradient > 60 mmHg was the only
      significant factor associated with re-intervention in group A (p=0.001).
      CONCLUSION: The results from balloon valvuloplasty in dysplastic pulmonary valve
      were suboptimal when compared to doming valves. However, it provides a high
      freedom from re-intervention rate in intermediate follow-up. Intervention at
      moderate severity can result in better outcome.

PMID- 25604364
TI  - Endocrine correlates of polycystic ovary syndrome in Pakistani women.
AB  - OBJECTIVE: To systematically examine the hormonal variations and their
      interactions in a local cohort of PCOS patients. STUDY DESIGN: A cross-sectional,
      analytical study. PLACE AND DURATION OF STUDY: King Edward Medical University and
      associated Mayo Hospital, Lahore, Pakistan, from June 2009 to May 2010.
      METHODOLOGY: The study comprised of 50 controls, 65 PCOS patients and 25 First
      Degree Relatives (FDRs) of patients, aged 18 - 45 years. Clinical examination,
      findings, detailed menstrual and family history was recorded through a
      comprehensive questionnaire followed by ovarian ultrasound examination. The blood
      samples were drawn for hormonal analysis by radioimmunoassay and
      immunoradiometric assay. RESULTS: Body mass index, Luteinizing Hormone (LH),
      LH:FSH ratio, insulin, testosterone, androstenedione and prolactin were
      significantly elevated in PCOS patients compared to control group. The FDRs of
      patients did not indicate significant variations when compared to control. LH and
      androstenedione were found to be significantly correlated. CONCLUSION: The
      gonadotrophins, LH to FSH ratio and androgens are dependable diagnostic
      parameters of PCOS. LH appears to be the most important in this regard, leading
      to hyperandrogenism.

PMID- 25604365
TI  - Pressure ulcers and their associated factors in nursing home inmates.
AB  - OBJECTIVE: To assess pressure ulcers and the associated risk factors, among the
      individuals who stayed at Yozgat Rehabilitation Care Center in Turkey. STUDY
      DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Yozgat Rehabilitation
      Care Center, Turkey, from August to September 2011. METHODOLOGY: One hundred and
      seventy five individuals participated in the study who received care at the above
      nursing home and agreed to participate in the study. The data were collected with
      an information form of descriptive characteristics (the form included a total of
      15 questions asked to get information about socio-demographic characteristics)
      and Braden risk assessment scale. For the data evaluation, Mann-Whitney U-test,
      Krushall-Wallis Variance analysis, Logistic Regression analysis were used.
      Statistical significance was defined by a probability level of p < 0.05. RESULTS:
      The mean score of Braden risk assessment scale of the individuals was 15.0 +/-
      3.3 and 16.0% were under very high risk. Nine (5.1%) had pressure ulcers. The
      average duration of stay was 2.17 +/- 0.80 years. Participants who were
      underweight, had lived at the rehabilitation center for a longer time, and were
      fed on regime 1, had a higher risk of developing pressure ulcers (p < 0.001).
      CONCLUSION: Individuals who stayed in nursing home were under very high risk of
      pressure ulcer. Pressure ulcers are preventable by the elimination of some risk
      factors and good nursing care. Such individuals should be periodically assessed
      in terms of risk.

PMID- 25604366
TI  - Thrombocytopenia in malaria: can platelet counts differentiate malaria from other
      infections?
AB  - OBJECTIVE: To determine the accuracy of thrombocytopenia as a diagnostic marker
      for malaria. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY:
      Department of Medicine, 1 Mountain Medical Battalion (Bagh, Azad Kashmir) from
      July to September 2013. METHODOLOGY: Adult patients presenting with a short
      history of fever without any localizing symptoms or signs were included.
      Exclusion criteria included patients with fever of > 7 days duration, those in
      whom an underlying diagnosis could be easily confirmed on the basis of history
      and physical examination, those on antibiotics/ antimalarials or antiplatelet
      agents and patients with Dengue fever. Platelet counts in venous whole blood
      samples were analysed with Sysmex KX-21 Haematology analyzer. Thick and thin
      peripheral blood smears were then prepared and examined for malarial parasites.
      Diagnosis of malaria was established on the basis of smear findings. RESULTS:
      There were 245 patients in total. Out of the 109 patients with thrombocytopenia,
      61 had vivax malaria. Platelets count was normal in 136 patients, including 4
      with vivax malaria. Falciparum malaria was not seen in any patient. All cases
      with malaria were uncomplicated. Various measures of accuracy thus calculated
      were sensitivity 93.85%, specificity 73.33%, positive predictive value 55.96%,
      negative predictive value 97.06%, positive likelihood ratio of 3.52, negative
      likelihood ratio of 0.08, diagnostic odds ratio 41.94 and diagnostic accuracy of
      78.78%. CONCLUSION: Thrombocytopenia has an excellent sensitivity and a very good
      specificity for vivax malaria. Normal platelet counts provide very strong
      evidence against malaria as the etiology of fever without a focus.

PMID- 25604367
TI  - Feedforward interview technique in obstetrics and gynaecology residents: a fact
      or fallacy.
AB  - OBJECTIVE: To determine the role of Feedforward Interview (FFI) technique in
      motivating residents of Obstetrics and Gynaecology for better learning and
      performance. STUDY DESIGN: An explorative study with mixed method approach being
      employed. PLACE AND DURATION OF STUDY: Department of Obstetrics and Gynaecology,
      Sandeman (Provincial) Hospital, Quetta, from November 2010 till May 2013.
      METHODOLOGY: Feedforward interview technique was complimented by survey
      questionnaire employing similar philosophy of FFI to triangulate data through two
      methods. Survey questionnaire was filled-up by 21 residents and analysed by SPSS
      version 17. Fourteen of these participants were identified for in-depth
      Feedforward Interviews (FFI), based on nonprobability purposive sampling after
      informed consent, and content analysis was done. RESULTS: Feedforward interview
      technique enabled majority of residents in recalling minimum of 3 positive
      experiences, mainly related to surgical experiences, which enhanced their
      motivation to aspire for further improvement in this area. Hard work was the main
      personal contributing factor both in FFI and survey. In addition to identifying
      clinical experiences enhancing desire to learn, residents also reported need for
      more academic support as an important factor which could also boost motivation to
      attain better performance. CONCLUSION: Feedforward interview technique not only
      helps residents in recalling positive learning experiences during their training
      but it also has a significant influence on developing insight about one's
      performance and motivating residents to achieve higher academic goals.

PMID- 25604368
TI  - Self-assessment through videotaping compared with peer and trainer feedback.
AB  - OBJECTIVE: To assess and compare three different types of feedback for
      presentation skills, self, peer and trainer feedback. STUDY DESIGN: Cross
      sectional study. PLACE AND DURATION OF STUDY: Faculty of Medicine at Ataturk
      University, Erzurum, Turkey, from March 2012 to December 2012. METHODOLOGY:
      Participants were faculty members and instructor nurses. Each participant gave a
      10-minute presentation, which was rated by peers, course trainers and the
      presenter himself/herself using a thirteen-item questionnaire (designed as a 5
      point Likert scale). Peers and trainers conducted the assessment during the
      presentation while the self-assessment was done later by watching a video
      recording of the presentation. Comparison of the points between the groups was
      made using the two-way ANOVA. Pearson correlation analysis was conducted to
      evaluate the relationship between the mean scores of self-assessment, peer and
      trainer assessment. RESULTS: Ten faculty members, 27 instructor nurses and 4
      trainers participated in the study. A total of 775 feedback reports were
      collected for 37 participants. There was no significant difference between the
      feedback scores of the evaluators as well as the occupation groups (p > 0.05).
      There was a strong positive and statistically significant correlation between
      trainer and peer (r = 0.73, p < 0.001). CONCLUSION: Consequently, there were no
      differences in the evaluations of presentation skills between different
      stakeholders. Trainers should use the video recording method to self-evaluate
      their presentation skills, and they should invite their peers from time to time
      to improve their own personal development by using peer review methods.

PMID- 25604369
TI  - Frequency of oronasal fistulae in complete cleft palate repair.
AB  - OBJECTIVE: To determine the frequency of oro-nasal fistula in patients undergoing
      complete cleft palate repair by two flappalatoplasty. STUDY DESIGN: Case series.
      PLACE AND DURATION OF STUDY: Department of Plastic Surgery, Services Hospital,
      Lahore, from January to December 2013. METHODOLOGY: Patients admitted to the
      study place for repair of cleft palate after informed consent obtained were
      included. Cleft palate was repaired by two-flap palatoplasty, using Bardach
      technique. Patients were discharged on the second postoperative day and followed
      up at third week postoperatively. During follow-up visits, fistulae formation and
      their sites were recorded on pre-designed proforma. RESULTS: Among the total 90
      patients, 40 patients (44.4%) were male and 50 patients (55.6%) were female. The
      mean age was 6.4 +/- 5.7 years ranging from 9 months to 20 years. At third week
      follow-up, 5 patients (5.6%) had fistulae formation. Four patients (80%) had
      anterior fistulae and one patient (20%) had posterior fistula. CONCLUSION: With
      two-flap palatoplasty Bardach procedure for repair of cleft palate, the
      complication of fistula formation was uncommon at 5.6%, provided the repair was
      tension free and multi-layered.

PMID- 25604370
TI  - Risk factors for deliberate self-harm in patients presenting to the emergency
      departments of Karachi.
AB  - OBJECTIVE: To determine the risk factors for Deliberate Self-Harm (DSH) in
      patients presenting to the Emergency Departments (EDs) of three tertiary care
      hospitals of Karachi, Pakistan. STUDY DESIGN: Multicentre matched case control
      study. PLACE AND DURATION OF STUDY: EDs of the Aga Khan University Hospital,
      Karachi, Civil Hospital, Karachi and Jinnah Postgraduate Medical Centre, Karachi,
      from March 2011 to February 2012. METHODOLOGY: A total of 201 cases and 201
      matched controls were taken from three hospitals situated in Karachi. All
      patients of 16 years and above presenting to the EDs of the hospitals with DSH
      attempt were invited to participate in the study. Controls were ED patients with
      complaints other than DSH. A control was matched with case for hospital, gender
      and age. Two questionnaires were used to collect information on the risk factors
      of DSH. Conditional Logistic Regression (CLR) was used to assess the association
      of various risk factors with DSH. RESULTS: Risk factors of DSH in Karachi
      included current history of mental disorder (OR = 4.53, 95% CI = 1.59 - 12.92),
      not sharing problems with someone (OR = 4.67, 95% CI = 2.4 - 9.0), living in
      rented houses (OR = 2.58, 95% CI = 1.37 - 4.84), Pathan ethnicity (OR = 5.05, 95%
      CI = 1.01-25.38) followed by others (OR = 3.88, 95% CI = 0.77 - 19.69) and Urdu
      speaking (OR = 2.71, 95% CI = 0.59 - 12.45). Absence of physical illness in the
      past month had an inverse association with DSH (OR = 0.17, 95% CI = 0.07 - 0.37).
      CONCLUSION: Mental illnesses, low socio-economic status and loneliness were the
      risk factors of DSH patients presenting to the three EDs of Karachi. Physical
      illness in the last month was protective against DSH in these patients.
      Psychiatric evaluation of DSH patients in the ED is important for early diagnosis
      and management of mental disorders.

PMID- 25604371
TI  - Pre-operative rectal indomethacin for reduction of postoperative nausea and
      vomiting after laparoscopic cholecystectomy: a double-blind randomized clinical
      trial.
AB  - OBJECTIVE: To evaluate the effect of pre-operative indomethacin suppository on
      postoperative nausea and vomiting in patients undergoing laparoscopic
      cholecystectomy. STUDY DESIGN: A double blind placebo-controlled randomized
      clinical trial. PLACE AND DURATION OF STUDY: Hazrat Rasoul Akram Hospital,
      Tehran, Iran, from February 2010 to September 2012. METHODOLOGY: One hundred and
      thirty patients, scheduled for laparoscopic cholecystectomy, were randomly
      divided into case and control groups. Sixty-five patients received indomethacin
      suppository and 70 patients received rectal placebo in the case and control
      groups respectively. All patients underwent the same protocol in laparoscopic
      surgery and anesthesia, then nausea and vomiting was recorded after 1, 6, 12 and
      24 hours postoperatively and compared between the two groups. Independent-sample
      t test or Mann-Whitney tests were used for statistical analysis. Level of
      statistical significance was set at P 2 0.05. RESULTS: Patients' nausea was
      statistically lower in the case group at the 1st hour (43.1 vs. 92.9%), 6th hour
      (20.0 vs. 68.6%) and 12th hour (7.7 vs. 24.3%) after surgery (for all periods, P
      < 0.001). Fewer patients in the case group experienced vomiting at the first
      (13.8 vs. 51.4%) and 6th hour (0 vs. 20%) after surgery (for both P < 0.001). The
      use of pethidine was also statistically less in the case group in the same hours
      after surgery (for all of them, P < 0.001). CONCLUSION: Rectal indomethacin
      before laparoscopic cholecystectomy led to lower postoperative nausea and
      vomiting.

PMID- 25604372
TI  - Comparison of Total Disc Replacement with lumbar fusion: a meta-analysis of
      randomized controlled trials.
AB  - A meta-analysis was performed to evaluate whether a beneficial clinical effect of
      the Total Disc Replacement (TDR) over lumbar fusion for the treatment of patients
      with Degenerative Disc Disease (DDD). An electronic search of PubMed, Cochrane
      Central Register of Controlled Trials, and EMBASE from their inception to 2012
      was completed, and we assessed risk bias and retrieved relevant data, and meta
      analysis was performed, if appropriate. Oswestry Disability Index (ODI), Visual
      Analog Score (VAS), patient satisfaction or VAS patient satisfaction, narcotic
      use, overall success rate, reoperation rate, work status, "surgery again?",
      complications and radiographic outcomes were evaluated. Six RCTs were included in
      this meta-analysis. At 2 years, TDR was demonstrated to be more beneficial for
      patients compared to lumbar fusion in the following outcomes, including ODI
      scores (MD:-4.87, 95% CI: -7.77 to -1.97, p=0.001), patient satisfaction
      (OR:1.91, 95% CI: 1.27 to 2.86, p=0.002) and VAS patient satisfaction (MD:9.10,
      95% CI: 3.20 to 14.99, p=0.002), the percentage of using narcotics (OR=0.54,
      95%CI: 0.31 to 0.96, p=0.03), overall success rate (OR:1.68, 95% CI: 1.26 to
      2.25, p=0.005), the rate of patients to chose the same surgical treatment again
      (OR:2.38, 95% CI: 1.72 to 3.28, p < 0.001), and complications (OR=0.50, 95%CI:
      0.29 to 0.84, p=0.008). Other outcomes, including re-operation rate (OR:0.62, 95%
      CI: 0.36 to 1.06, p=0.08) and work status (OR=1.05, 95% CI: 0.75 to 1.47,
      p=0.80), were demonstrated to be no differences between the two groups. In a long
      term of follow-up (2 years), TDR shows a significant superiority for the
      treatment of lumbar DDD compared with fusion. 

PMID- 25604373
TI  - Modified single stapler technique in anterior resection for rectal cancer.
AB  - Technical difficulties during colorectal surgery increase the complication rates.
      We introduce a modified single stapler technique for patients in whom technical
      problems are encountered while performing double stapler technique. Before pelvic
      dissection, descending colon is divided at minimum 10 cm proximal to the tumoral
      segment. Tumor specific mesorectal excision is performed and two purse string
      sutures are placed at the distal margin with an interval of 1 - 2 cm. After
      introducing a circular stapler via the anus, the distal purse string suture is
      tied around the central shaft of the stapler and the proximal purse string suture
      around the colonic lumen. After the resection is completed between the two
      sutures, the anvil shaft is connected to the central shaft and the stapler is
      closed and fired. None of the patients had an anastomotic leak. This technique
      may be a safe alternative particularly in patients with narrow pelvis and distal
      tumors. 

PMID- 25604374
TI  - Ovarian dermoid causing pilimiction.
AB  - Ovarian dermoid cyst is one of the common problems seen in gynaecology, they make
      upto 10 - 25% of all ovarian neoplasms and are usually seen in younger age group.
      Mature cystic teratomas are usually an incidental finding during a clinical
      examinations, radiographic studies or during abdominal operations performed for
      other indications. Other presentations include abdominal symptoms from
      complications of the cyst such as torsion, rupture, infection and malignant
      transformation. Dermoid cyst in urinary bladder is a very rare condition. Here we
      are presenting a case report of a female who presented with lower abdominal pain
      and passage of hair in urine (pilimiction). Upon investigations it was found that
      patient had right sided dermoid which had penetrated the wall of bladder and
      expelled its contents in the bladder. This was a very rare presentation and no
      such case has been reported in Pakistani literature. 

PMID- 25604375
TI  - Cerebral salt wasting: a report of three cases.
AB  - Hyponatremia secondary to the Syndrome of Inappropriate Anti-Diuretic Hormone
      (SIADH) secretion is commonly observed in patients with various neurological
      disorders. Cerebral Salt Wasting (CSW) resulting in hyponatremia is also an
      infrequent occurrence in some patients with neurological disorders. Confusion in
      differentiating CSW from SIADH may arise since both results in similar
      electrolyte disturbances. Herein, we report three cases of CSW with intracranial
      afflictions. CSW was diagnosed on the basis of fractional excretion of urinary
      sodium and uric acid along with extremely low serum uric acid. Improvements in
      serum sodium levels after saline hydration and fludrocortisone administration
      further supported the diagnosis. 

PMID- 25604376
TI  - Ileo-ileal intussusception in a premature neonate: an unusual cause of NEC in
      premature babies.
AB  - Intussusception is a rare entity in neonates. It may present with non-specific
      signs including abdominal distension, feeding intolerance, vomiting and bloody
      stools. Symptomatology is similar to Necrotizing Entero-Colitis (NEC). Ultrasound
      can help to establish early diagnosis in neonate. A 27-week preterm newborn was
      initially suspected as NEC based on abdominal distention, bilious vomiting,
      worsening clinical condition and dilated loops of bowel on X-ray, which turned
      out to be ileo-ileal intussusception. Diagnosis was made by ultrasound obtained
      for a palpable mass to rule out intra abdominal abscess and lack of improvement
      in clinical condition despite 5 days of conservative treatment. Surgery was
      performed consisting of removal of the necrotic intussusception area and end-to
      end anastomosis and patient was discharged from hospital on day 60 of life. As a
      conclusion, pathological abdominal findings in preterm newborns can also be due
      to conditions other than NEC and ultrasound may be a useful tool for timely and
      accurate diagnosis. 

PMID- 25604377
TI  - Cost-effective treatment of genotype-3 chronic hepatitis C.

PMID- 25604378
TI  - Role of training, trainer and trainee in the future of histopathology in
      Pakistan.

PMID- 25604379
TI  - The changing face of medical education: are we ready?

PMID- 25604380
TI  - Giant splenic artery aneurysm.

PMID- 25604381
TI  - Light microscopy and scanning electron microscopy study on microstructure of
      gallbladder mucosa in pig.
AB  - The present light microscopy (LM) and scanning electron microscopy (SEM) studies
      on porcine gallbladder mucosa provide a description of the microstructures of
      great functional importance such as mucosal folds, the epithelium, glands, and
      lymphatic nodules. The results showed the regional structural differences of the
      porcine gallbladder wall. Depending on the part of the gallbladder, three types
      of mucosal structures were described: simple and branched folds and mucosal
      crypts. An important structural feature found in the mucosa is connected with the
      structural variety of type of mucosal folds, which change from simple located in
      the neck, to most composed, i.e., branched or joined, in the polygonal crypts
      toward the fundus of the gallbladder. The morphometric analysis showed
      statistically significantly differences in the form and size of the folds and
      between the fundus, body, and neck of the gallbladder. Differences in the size of
      mucosal epithelium are discussed in terms of processes of synthesis and secretion
      of glycoproteins. Regional, species-specific differences in morphology of mucosal
      subepithelial glands, i.e., their secretory units and openings, and intensity of
      mucus secretion were described. Our results on the pig gallbladder show
      adaptation and/or specialization in particular areas of the mucosa for (1)
      secretion of mucus in the neck or body of gallbladder and (2) for cyclic volume
      changes, especially in the fundus of gallbladder. The description of the
      microstructures of mucosa in the porcine gallbladder could be useful as reference
      data for numerous experiments on the bile tract in the pig.

PMID- 25604383
TI  - Expedient synthesis of 3-phenylbicyclo[1.1.1]pentan-1-amine via metal-free
      homolytic aromatic alkylation of benzene.
AB  - Recently, the potential utility of the BCP motif, as a contemporary lead
      optimization tactic, has generated substantial interest in medicinal chemistry.
      To facilitate this inquisitiveness, the concomitant development of efficient
      synthetic protocols is crucial. The following work discloses a new, expedient and
      versatile approach to one such potentially useful BCP derivative. 

PMID- 25604382
TI  - Photocoagulation of human retinal pigment epithelium in vitro: unravelling the
      effects on ARPE-19 by transcriptomics and proteomics.
AB  - PURPOSE: Despite the extensive use of retinal photocoagulation for ischaemia and
      vascular leakage in retinal vascular disease, the molecular mechanisms behind its
      clinical beneficial effects are still poorly understood. One important target of
      laser irradiation is the retinal pigment epithelium (RPE). In this study, we
      aimed at identifying the isolated effects of photocoagulation of RPE at both the
      mRNA and protein expression levels. METHODS: Human ARPE-19 cells were exposed to
      photocoagulation. Gene expression and protein expression were compared to
      untreated cells using microarray and liquid chromatography-mass spectrometry
      analysis. Genes and proteins queried by microarray and mass spectrometry were
      subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway
      analyses. RESULTS: Laser irradiation resulted in an induction of the
      cytoprotective heat-shock protein subfamily Hsp70 as well as in a suppression of
      the vascular permeability factor carbonic anhydrase 9 (CA9). These expression
      patterns were evident at both the mRNA and protein levels. KEGG pathway analyses
      revealed genes and proteins involved in cellular turnover, repair and
      inflammation. CONCLUSIONS: By characterizing the transcriptional and
      translational effects of laser coagulation on the RPE cells in culture, we have
      revealed responses, which might contribute to some of the beneficial effects
      obtained by photocoagulation for ischaemia and vascular leakage in retinal
      vascular disease.

PMID- 25604385
TI  - A Synthetic Heterobivalent Ligand Composed of Glucagon-Like Peptide 1 and
      Yohimbine Specifically Targets beta Cells Within the Pancreas.
AB  - PURPOSE: beta Cell specificity for a heterobivalent ligand composed of glucagon
      like peptide-1 (GLP-1) linked to yohimbine (GLP-1/Yhb) was evaluated to determine
      its utility as a noninvasive imaging agent. PROCEDURES: Competition binding
      assays were performed on betaTC3 cells and isolated rat islets. Immunostaining
      for insulin was used to co-localized intravenously injected Cy5-labeled GLP-1/Yhb
      in beta cells of Sprague-Dawley rats. Rats were intravenously injected with In
      111-labeled GLP-1/Yhb to determine clearance rates and tissue biodistribution.
      Tissue-specific binding was confirmed by competition with pre-administration of
      unlabeled GLP-1/Yhb and in Streptozotocin-induced diabetic rats. RESULTS: In
      betaTC3 cells, high affinity binding of GLP-1/Yhb required interactions with both
      receptors because monovalent competition or receptor knockdown with RNAi lowered
      specificity and avidity of the heterobivalent ligand. Binding specificity for
      isolated islets was 2.6-fold greater than that of acinar tissue or islets pre
      incubated with excess unlabeled GLP-1/Yhb. Immunofluorescent localization of Cy5
      labeled GLP-1/Yhb was restricted to pancreatic islets. Within 30 min, ~90% of the
      In-111-labeled GLP-1/Yhb was cleared from blood. Tissue-specific accumulation of
      radiolabeled ligand was apparent in the pancreas, but not in other tissues within
      the abdominal imaging field. Pancreas specificity was lost in Streptozotocin
      induced diabetic rats. CONCLUSIONS: The GLP-1/Yhb exhibits high specificity for
      beta cells, rapid blood clearance rates, and low non-specific uptake by other
      tissues within the abdominal imaging field. These characteristics of GLP-1/Yhb
      are desirable for application to beta cell imaging in vivo and provide a basis
      for developing additional multivalent beta cell-specific targeting agents to aid
      in the management of type 1 diabetes.

PMID- 25604386
TI  - A Hyaluronic Acid-Conjugated Gadolinium Hepatocyte-Specific T1 Contrast Agent for
      Liver Magnetic Resonance Imaging.
AB  - PURPOSE: In this study, we synthesized hyaluronic acid-conjugated gadolinium (HA
      diethylene triamine pentaacetic acid (DTPA)-Gd) and evaluated as hepatocyte
      specific magnetic resonance imaging (MRI) contrast agent for the diagnosis of
      hepatic metastasis. PROCEDURES: We conducted Fourier transform (FT)-IR analysis
      to determine the conjugation of HA and DTPA and performed cell viability assays
      using NIH3T3 and FL83B cell lines. We also conducted T1-weighted MRI of HA-DTPA
      Gd and gadoxetic acid to compare the paramagnetic properties of both. RESULTS: HA
      DTPA-Gd had a higher efficiency in liver MRI compared with the commercially
      available liver-specific contrast agent (p < 0.001). HA-DTPA-Gd, which possessed
      a higher T1 relaxivity, showed excellent capability for the diagnosis of hepatic
      metastasis through an in vivo MRI study in comparison with gadoxetic acid (p <
      0.001). CONCLUSION: Based on this study, we believe that HA-DTPA-Gd has promising
      potential for use as a contrast agent for liver MRI of hepatic metastases.

PMID- 25604387
TI  - Subcutaneous vaccination with Porphyromonas gingivalis ameliorates periodontitis
      by modulating Th17/Treg imbalance in a murine model.
AB  - To date, Porphyromonas gingivalis (P. gingivalis) vaccination has been studied
      only in animals, and no effective prophylactic human periodontal vaccine has been
      developed, with the reason for the failure of prophylactic human periodontal
      vaccines unknown. T helper 17 cell (Th17)/regulatory T (Treg) cell responses play
      an important role in the development of periodontitis, and a Th17/Treg imbalance
      causes the pathogenesis of periodontitis. However, whether vaccination with P.
      gingivalis can prevent periodontitis through modulation of the Th17/Treg
      imbalance remains unknown. In this study, mice were subcutaneously vaccinated
      with formalin-killed P. gingivalis and then orally challenged with P. gingivalis.
      The vaccination protected the mice from alveolar bone resorption and
      inflammation. These protective effects might be ascribed to downregulation of
      Th17 cells and interleukin (IL)-17A production, upregulation of Treg and receptor
      activator of nuclear factor-kappa B ligand (RANKL)(+)CD4(+)T cells, and IL-10 and
      transforming growth factor-beta1 production, and inhibition of lymphocyte
      proliferation. Our findings may provide a direction for the development of a
      vaccine or therapy against periodontitis by alteration of the Th17/Treg
      imbalance. 

PMID- 25604389
TI  - A General Strategy toward Carbon Cloth-Based Hierarchical Films Constructed by
      Porous Nanosheets for Superior Photocatalytic Activity.
AB  - Herein, the controlled synthesis of 3D hierarchical films on carbon cloth (CC) in
      a high yield through a hydrothermal process and their high photocatalytic
      properties are reported. As representative examples, the obtained ZnIn2 S4 /CdIn2
      S4 composites are composed of porous nanosheets. During the hydrothermal process,
      l-cysteine plays an important dual role as a coordinating agent and sulfur
      source, which is in favor of adjusting stoichiometry of the final product and
      forming the nanoporous structure. This facile method can be extended to
      synthesize other sulfides and oxides on CC substrates, such as CoIn2 S4 , MnIn2
      S4 , FeIn2 S4 , SnS2 , and Bi2 WO6 . When evaluated the photocatalytic activity,
      the optimized ZnIn2 S4 /CdIn2 S4 (20%)-CC with an easily recycling feature shows
      higher photocatalytic degradation activity for methylene blue (MB) than ZnIn2 S4 
      CC, CdIn2 S4 -CC, and ZnIn2 S4 /CdIn2 S4 (20%) powder. More importantly, ZnIn2 S4
      /CdIn2 S4 (20%)-CC also exhibits superior H2 production activity. The enhanced
      photocatalytic activity is attributed to the unique porous sheet-like structure
      and the formation of heterojunction. Our results could provide a promising way to
      develop high-performance photocatalytic films, which makes it possible to be used
      in real devices. 

PMID- 25604388
TI  - Vasopressin receptor antagonists.
AB  - Arginine vasopressin (AVP) is the principal hormone involved in regulating the
      tonicity of body fluids. Less appreciated is the role that AVP plays in a variety
      of other physiologic functions including glucose metabolism, cardiovascular
      homeostasis, bone metabolism, and cognitive behavior. AVP receptor antagonists
      are now available and currently approved to treat hyponatremia. There is a great
      deal of interest in exploring the potential benefits that these drugs may play in
      blocking AVP-mediated effects in other organ systems. The purpose of this report
      is to provide an update on the expanding role of AVP receptor antagonists and
      what disease states these drugs may eventually be used for. 

PMID- 25604391
TI  - Radiogenomics helps to achieve personalized therapy by evaluating patient
      responses to radiation treatment.
AB  - Radiogenomics is the whole genome application of radiogenetics, which focuses on
      uncovering the underlying genetic causes of individual variation in sensitivity
      to radiation. There is a growing consensus that radiosensitivity is a complex,
      inherited polygenic trait, dependent on the interaction of many genes involved in
      multiple cell processes. An understanding of the genes involved in processes such
      as DNA damage response and oxidative stress response, has evolved toward
      examination of how genetic variants, most often, single nucleotide polymorphisms
      (SNPs), may influence interindividual radioresponse. Many experimental
      approaches, such as candidate SNP association studies, genome-wide association
      studies and massively parallel sequencing are being proposed to address these
      questions. We present a review focusing on recent advances in association studies
      of SNPs to radiotherapy response and discuss challenges and opportunities for
      further studies. We also highlight the clinical perspective of radiogenomics in
      the future of personalized treatment in radiation oncology. 

PMID- 25604390
TI  - Aberrant loss of dickkopf-3 in gastric cancer: can it predict lymph node
      metastasis preoperatively?
AB  - BACKGROUND: Dickkopf-3 (DKK3) may act as a tumor suppressor as it is down
      regulated in various types of cancer. This study assessed the DKK3 protein
      expression in gastric cancer and its potential value as a prognostic marker.
      METHODS: DKK3 expression was evaluated by immunohistochemistry in 158 gastric
      cancer samples from patients who underwent gastrectomy from 2002 to 2008.
      Clinicopathological parameters and survival data were analyzed. RESULTS: Loss of
      DKK3 expression was found in 64 of 158 (40.5%) samples, and it was associated
      with advanced T stage (p < 0.001), lymph node metastasis (p < 0.001), UICC TNM
      stage (p < 0.001), tumor location (p = 0.029), lymphovascular invasion (p =
      0.035), and perineural invasion (p = 0.032). Patients without DKK3 expression in
      tumor cells had a significantly worse disease-free and overall survival than
      those with DKK3 expression (p < 0.001, and p = 0.001, respectively). TNM stage (p
      = 0.028 and p < 0.001, respectively) and residual tumor (p < 0.001 and p = 0.003,
      respectively) were independent predictors of disease-free and overall survival.
      Based on the preoperative clinical stage assessed by computed tomography (CT),
      loss of DKK3 expression was predominantly associated with worse prognosis in
      patients with clinically node-negative advanced gastric cancer (AGC). The
      combination of DKK3 expression status and CT increased the accuracy of CT staging
      for predicting lymph node involvement from 71.5 to 80.0% in AGC patients.
      CONCLUSION: Loss of DKK3 protein expression was significantly associated with
      poor survival in patients with gastric cancer and was strongly correlated with
      the TNM stage. DKK3 might be a potential biomarker of lymph node involvement that
      can improve the predictive power of CT.

PMID- 25604392
TI  - Quantitative determination of irinotecan and the metabolite SN-38 by nanoflow
      liquid chromatography-tandem mass spectrometry in different regions of
      multicellular tumor spheroids.
AB  - A new and simple method was developed to evaluate the distribution of
      therapeutics in three-dimensional multicellular tumor spheroids (MCTS) by
      combining serial trypsinization and nanoflow liquid chromatography-tandem mass
      spectrometry (nLC-MS/MS). This methodology was validated with quantitative
      measurements of irinotecan and its bioactive metabolite, SN-38, in distinct
      spatial regions of HCT 116 MCTS. Irinotecan showed a time-dependent permeability
      into MCTS with most of the drug accumulating in the core after 24 h of treatment.
      The amount of SN-38 detected was 30 times lower than that of the parent drug, and
      was more abundant in the outer rim and intermediate regions of MCTS where
      proliferating cells were present. This method can be used to investigate novel
      and established drugs. It enables investigation of drug penetration properties
      and identification of metabolites with spatial specificity in MCTS. The new
      approach has great value in facilitating the drug evaluation process. 

PMID- 25604394
TI  - Preactivated thiomers: their role in drug delivery.
AB  - INTRODUCTION: Since thiolated polymers - known as thiomers - have entered the
      pharmaceutical arena in the late 1990 s, more and more academic and industrial
      research groups have started to work with these promising polymeric excipients.
      Meanwhile, various thiomers are the subject of clinical trials and the first
      product based on thiolated chitosan will reach the market in 2015. Due to the
      formation of disulfide bonds with mercaptopyridine substructures, thiol groups of
      thiomers are on the one hand more reactive and on the other hand are protected
      toward oxidation. These so-called preactivated thiomers representing the second
      generation of thiomers are subject of this review. AREAS COVERED: Within this
      review, preactivated thiomers are classified and their mode of action is
      described. Furthermore, different synthetic pathways, purification and chemical
      characterization methods of preactivated thiomers are explained. Their properties
      including mucoadhesive, permeation-enhancing, efflux pump inhibitory and in situ
      gelling properties are described. In addition, various formulations based on
      preactivated thiomers are introduced. EXPERT OPINION: The first-generation
      thiomers have already shown great potential resulting in various product
      developments. Preactivated thiomers - representing the second generation of
      thiomers - offer the additional advantage of even comparatively more reactive
      sulfhydryl ligands and of stability toward oxidation. According to this, they are
      promising novel polymeric excipients for various applications.

PMID- 25604393
TI  - Fingerprinting desmosine-containing elastin peptides.
AB  - Elastin is a vital protein of the extracellular matrix of jawed vertebrates and
      provides elasticity to numerous tissues. It is secreted in the form of its
      soluble precursor tropoelastin, which is subsequently cross-linked in the course
      of the elastic fiber assembly. The process involves the formation of the two
      tetrafunctional amino acids desmosine (DES) and isodesmosine (IDES), which are
      unique to elastin. The resulting high degree of cross-linking confers remarkable
      properties, including mechanical integrity, insolubility, and long-term stability
      to the protein. These characteristics hinder the structural elucidation of mature
      elastin. However, MS(2) data of linear and cross-linked peptides released by
      proteolysis can provide indirect insights into the structure of elastin. In this
      study, we performed energy-resolved collision-induced dissociation experiments of
      DES, IDES, their derivatives, and DES-/IDES-containing peptides to determine
      characteristic product ions. It was found that all investigated compounds yielded
      the same product ion clusters at elevated collision energies. Elemental
      composition determination using the exact masses of these ions revealed molecular
      formulas of the type CxHyN, suggesting that the pyridinium core of DES/IDES
      remains intact even at relatively high collision energies. The finding of these
      specific product ions enabled the development of a similarity-based scoring
      algorithm that was successfully applied on LC-MS/MS data of bovine elastin
      digests for the identification of DES-/IDES-cross-linked peptides. This approach
      facilitates the straightforward investigation of native cross-links in elastin. 

PMID- 25604395
TI  - A short scalable route to (-)-alpha-kainic acid using Pt-catalyzed direct allylic
      amination.
AB  - An increased supply of scarce or inaccessible natural products is essential for
      the development of more sophisticated pharmaceutical agents and biological tools,
      and thus the development of atom-economical, step-economical and scalable
      processes to access these natural products is in high demand. Herein we report
      the development of a short, scalable total synthesis of (-)-alpha-kainic acid, a
      useful compound in neuropharmacology that is, however, limited in supply from
      natural resources. The synthesis features sequential platinum-catalyzed direct
      allylic aminations and thermal ene-cyclization, enabling the gram-scale synthesis
      of (-)-alpha-kainic acid in six steps and 34% overall yield.

PMID- 25604396
TI  - Chemical shift perturbations induced by residue specific mutations of CaM
      interacting with NOS peptides.
AB  - The regulation of nitric oxide synthase (NOS) by calmodulin (CaM) plays a major
      role in a number of key physiological and pathological processes. A detailed
      molecular level picture of how this regulation is achieved is critical for drug
      development and for our understanding of protein regulation in general. CaM is a
      small acidic calcium binding protein and is required to fully activate NOS. The
      exact mechanism of how CaM activates NOS is not fully understood at this time.
      Studies have shown CaM to act like a switch that causes a conformational change
      in NOS to allow for the electron transfer between the reductase and oxygenase
      domains through a process that is thought to be highly dynamic. The interaction
      of CaM with NOS is modified by a number of post-translation modifications
      including phosphorylation. Here we present backbone and sidechain (1)H, (15)N NMR
      assignments of modified CaM interacting with NOS peptides which provides the
      basis for a detailed study of CaM-NOS interaction dynamics using (15)N relaxation
      methods. 

PMID- 25604398
TI  - Is it useful to also image the asymptomatic leg in patients with suspected deep
      vein thrombosis?
AB  - BACKGROUND: Venous ultrasonography is the cornerstone of the diagnostic work-up
      in patients with suspected deep vein thrombosis (DVT). Significant variations
      exist in clinical practice between centers and/or countries, e.g. proximal vs.
      whole-leg ultrasound, serial tests vs. single test, and combination with clinical
      probability and D-dimer testing. Fewer data exist on the need for bilateral leg
      imaging. OBJECTIVES: To assess the yield of bilateral leg ultrasonography in
      patients with suspected DVT. PATIENTS AND METHODS: This was a retrospective
      cohort study of consecutive patients with clinically suspected DVT. A single
      whole-leg ultrasound scan was performed in all patients. We extracted information
      on demographics, risk factors, clinical signs, pretest probability, side of
      clinical suspicion, and ultrasound results. RESULTS AND CONCLUSIONS: Among the
      2804 included patients, 609 (21.8%) patients had a positive ultrasound finding. A
      total of 20 patients (0.8%; 95% confidence interval [CI] 0.5-1.2%) had a thrombus
      diagnosed in both the symptomatic leg and asymptomatic leg. Moreover, five
      patients (0.2%; 95% CI 0.1-0.5%) did not have a thrombus in the symptomatic leg
      but had a thrombus in the asymptomatic leg. Two of 2540 patients with unilateral
      symptoms had no proximal DVT in the symptomatic leg and a proximal DVT in the
      asymptomatic leg (0.08%; 95% CI 0.0-0.3%). In summary, systematic imaging of both
      legs in patients with suspected DVT has a very low yield, and therefore does not
      appear to be justified.

PMID- 25604397
TI  - Fish oil supplements in New Zealand are highly oxidised and do not meet label
      content of n-3 PUFA.
AB  - We evaluated the quality and content of fish oil supplements in New Zealand. All
      encapsulated fish oil supplements marketed in New Zealand were eligible for
      inclusion. Fatty acid content was measured by gas chromatography. Peroxide values
      (PV) and anisidine values (AV) were measured, and total oxidation values (Totox)
      calculated. Only 3 of 32 fish oil supplements contained quantities of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that were equal or
      higher than labelled content, with most products tested (69%) containing <67%.
      The vast majority of supplements exceeded recommended levels of oxidation
      markers. 83% products exceeded the recommended PV levels, 25% exceeded AV
      thresholds, and 50% exceeded recommended Totox levels. Only 8% met the
      international recommendations, not exceeding any of these indices. Almost all
      fish oil supplements available in the New Zealand market contain concentrations
      of EPA and DHA considerably lower than claimed by labels. Importantly, the
      majority of supplements tested exceeded the recommended indices of oxidative
      markers. Surprisingly, best-before date, cost, country of origin, and exclusivity
      were all poor markers of supplement quality. 

PMID- 25604399
TI  - Epidemiology of invasive fungal infections in lung transplant recipients on long
      term azole antifungal prophylaxis.
AB  - Lung transplant recipients (LTR) at our institution receive prolonged and mostly
      lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic
      strategy on the epidemiology and outcome of invasive fungal infections (IFI) is
      unknown. This was a single-center, retrospective cohort study. We reviewed the
      medical records of all adult LTR from January 2002 to December 2011. Overall,
      16.5% (15 of 91) of patients who underwent lung transplantation during this time
      period developed IFI. Nineteen IFI episodes were identified (eight proven, 11
      probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with
      idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI:
      1.15-15.91; p = 0.03). A higher hazard of mortality was observed among those who
      developed IFI, although this was not statistically significant (hazard ratio
      [HR]: 1.71; 95% confidence interval [CI] [0.58-4.05]; p = 0.27). Aspergillus
      fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being
      the most common site of infection. None of our patients developed disseminated
      invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue
      to occur in LTR, and the eradication of IFI appears to be challenging even with
      prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF
      exposure. 

PMID- 25604401
TI  - Prevalence of gastroesophageal reflux disease in Moscow.
AB  - Limited data exist to determine the prevalence and clinical spectrum of
      gastroesophageal reflux disease (GERD) in the Russian population, which might be
      different from those in Western countries. This study was performed in Moscow on
      randomized 1065 adults aged >= 15 years. A validated reflux questionnaire
      comprising 72 questions and an additional 29 sub-questions were used. The
      questions assessed (heartburn and regurgitation) and related (dyspepsia,
      dysphagia, odynophagia and chest pain) symptoms, the triggering factors of these
      symptoms, family history and data on demographic and socioeconomic features. GERD
      was defined as heartburn and/or regurgitation once a week or common. Of the 1065
      participants, 42.1% were male and 57.9% were female. The prevalences of frequent
      and occasional symptoms were 17.6 and 22.1% for heartburn and 17.5 and 21.8% for
      regurgitation, respectively, over the last 12 months. The prevalence of GERD was
      found to be 23.6%. The rate of GERD was significantly higher in females than in
      males (15.4 vs. 29.5%, P < 0.001) and significantly increased as the age of the
      participants increased (P = 0.011). GERD was present in 20.4% of smokers, 24.2%
      of coffee drinkers, 21.5% of alcohol consumers and 45.9% of stressed
      participants. Although the rate of alcohol consumers was lower in those with GERD
      compared with those without GERD, the rate of coffee drinkers and stressed
      participants was higher among those with GERD. The rate of additional symptoms
      was higher even in participants complaining of regurgitation/heartburn rarely,
      compared with those without complaints. Using the same questionnaire, which makes
      it possible to compare the present results with those from different countries,
      we found the prevalence of GERD in Moscow to be 23.6%, one of highest in the
      Western populations. The rates of heartburn and regurgitation were found to be
      similar, which constitutes a different result than has been found in similar
      studies. Additional symptoms should be assessed, in all GERD patients even in the
      presence of rare complaints of regurgitation/heartburn.

PMID- 25604402
TI  - Venous hypertension in syndromic and complex craniosynostosis: the abnormal
      anatomy of the jugular foramen and collaterals.
AB  - Why craniosynostosis patients develop elevated intracranial pressure (ICP) is
      still a mystery. Our aim was to investigate jugular foramen size and its relation
      to venous hypertension and elevated ICP. Secondly, we evaluated whether occipital
      collateral veins develop as a compensatory mechanism for elevated ICP. We
      conducted a prospective study in 41 children with craniosynostosis who underwent
      a 3D-CT-angiography. We evaluated the anatomical course of the jugular vein, the
      diameter of the jugular foramen and the relation to the presence of papilledema.
      Additionally, we studied the anatomical variations of the cerebral venous
      drainage system. The diameter of the jugular foramen was significantly smaller in
      our patients. Abnormal venous collaterals were most often observed in patients
      with Apert, Crouzon-Pfeiffer and Saethre-Chotzen syndrome, even in children under
      two years of age. There was no significant difference in the number of collateral
      veins in patients with or without papilledema. Collaterals appear to reflect an
      inborn abnormality of the venous system, rather than a compensating mechanism for
      elevated ICP. This study confirms the presence of jugular foraminal narrowing in
      craniosynostosis patients and an abnormal venous system, which may predispose to
      elevated ICP. LEVEL OF EVIDENCE: Diagnostic II.

PMID- 25604403
TI  - [In Process Citation].

PMID- 25604404
TI  - [In Process Citation].

PMID- 25604405
TI  - [In Process Citation].

PMID- 25604406
TI  - Causes of total and permanent disability in middle-aged adult workers affiliated
      with the Mexican Social Security Institute in Baja California, Mexico.

PMID- 25604407
TI  - Association between perceived mental stress and physical activity in elderly
      Korean people.

PMID- 25604408
TI  - [In Process Citation].

PMID- 25604409
TI  - Health impact assessment of decreases in PM10 and ozone concentrations in the
      Mexico City Metropolitan Area: a basis for a new air quality management program.
AB  - OBJECTIVE: To conduct a health impact assessment (HIA) to quantify health
      benefits for several PM and O3 air pollution reduction scenarios in the Mexico
      City Metropolitan Area (MCMA). Results from this HIA will contribute to the
      scientific support of the MCMA air quality management plan (PROAIRE) for the
      period 2011-2020. MATERIALS AND METHODS: The HIA methodology consisted of four
      steps: 1) selection of the air pollution reduction scenarios, 2) identification
      of the at-risk population and health outcomes for the 2005 baseline scenario, 3)
      selection of concentration-response functions and 4) estimation of health
      impacts. RESULTS: Reductions of PM10 levels to 20 MUg/m3 and O3 levels to
      0.050ppm (98 ug/m3) would prevent 2300 and 400 annual deaths respectively. The
      greatest health impact was seen in the over-65 age group and in mortality due to
      cardiopulmonary and cardiovascular disease. CONCLUSION: Improved air quality in
      the MCMA could provide significant health benefits through focusing interventions
      by exposure zones.

PMID- 25604410
TI  - [A decade of lead monitoring in schoolchildren in the metropolitan area of
      Monterrey NL, Mexico].
AB  - OBJECTIVE: To establish the blood lead concentration and associated risk factors
      in schoolchildren during 1998 and 2008. MATERIALS AND METHODS: A blood lead
      screening was conducted in schoolchildren of 6-12 years of age, enrolled in 17
      elementary schools of the metropolitan area of Monterrey, Mexico, during 1998 and
      2008. RESULTS: The mean blood lead level were 9.6 +/- 3.0 (ug/dL range of 3.18 to
      20.88) in 1998 and 4.5+/-4.8 ug/dL (range of 3.3 to 53.7) showing a 2.1-times
      reduction in blood lead levels (p<0.01). CONCLUSIONS: This reduction in blood
      lead levels demonstrate environmental and industrial control improvements and the
      benefits of fading out the leaded gasoline during the 1990's.

PMID- 25604411
TI  - Self-rated health in Brazilian adults and elderly: data from the National
      Household Sample Survey 2008.
AB  - OBJECTIVE: To investigate prevalence of poor self-rated health and its
      association with individual and household-level characteristics among adults and
      elderly in Brazil. MATERIALS AND METHODS: Cross-sectional study with Brazilian
      National Household Sample Survey 2008 (n=257 816). Crude and multilevel-adjusted
      Poisson regression models were fitted. RESULTS: After adjusted analysis, poor
      self-rated health was significantly associated with higher household income,
      living alone, not having piped water nor garbage collection, lower education, not
      having health insurance, female sex, higher age, being a current or previous
      smoker, physical inactivity, having chronic diseases, having physical impairment.
      Subjects living in rural areas also had higher prevalence of poor self-rated
      health. The factors most strongly associated with the outcome were physical
      impairment and reporting three or more chronic diseases. CONCLUSIONS:
      Socioeconomic, health related behaviors, and physical health were associated with
      poor self-rated health.

PMID- 25604412
TI  - Direct medical costs of neonatal respiratory distress syndrome in two specialized
      public hospitals in Mexico.
AB  - OBJECTIVE: To estimate direct medical costs (DMC) associated with treatment of
      Respiratory Distress Syndrome (RDS) in newborns (NB) in two specialized public
      hospitals in Mexico. MATERIALS AND METHODS: The perspective used was health care
      payer. We estimated DMC associated with RDS management. The pattern of resource
      use was established by reviewing clinical records. Microcosting and bootstrap
      techniques were used to obtain the DMC. Estimated costs were reported in 2011 US
      dollars. RESULTS: Average DMC per RDS event was 14 226 USD. The most significant
      items that account for this cost were hospitalization (38%), laboratory and
      diagnostic exams (18%), incubator time (10%), surfactant therapy (7%), and
      mechanical ventilation (7%). CONCLUSION: Average DMC in NB with RDS fluctuated in
      relation to gestational age weight at birth and clinical complications presented
      by patients during their hospitalization.

PMID- 25604413
TI  - [Seroprevalence and detection of primary infection by cytomegalovirus with IgG
      avidity test during the first quarter of pregnancy].
AB  - OBJECTIVE: To determine the seroprevalence and detection of primary infection by
      cytomegalovirus (CMV) with immunoglobulin G (IgG) avidity test during the first
      quarter of pregnancy in the General Hospital in Morelia, Michoacan. MATERIALS AND
      METHODS: A total of 177 patients were studied employing a modified Elisa test
      using a chemiluminescent microparticle immunoassay (CMIA) for the detection of
      CMV antibodies (IgG and immunoglobulin M [IgM]), and IgG avidity. RESULTS: 90.4%
      were positive for IgG, and of these, 2.3% were also reactive for IgM, and in this
      group the IgG avidity test reported low avidity for 1.1% and higher avidity in
      the same percentage. 9.6% were seronegative. CONCLUSIONS: Similarity was found
      with published studies in Mexico. Health professionals should know the clinical
      algorithms for diagnosis and proper management of CMV infection using the IgG
      avidity test.

PMID- 25604415
TI  - [Institutional abuse toward the elderly: perceptions of health care providers and
      older adults].
AB  - OBJECTIVE: To analyze the health care providers (HCP) and elderly patients'
      perceptions about abuse of the elderly by health personnel of public health
      services, in selected cities in Mexico. MATERIALS AND METHODS: A qualitative
      study and a strategy of data triangulation were performed during 2009 and 2012;
      13 HCPs and 12 elders were interviewed, in order to obtain their experience
      regarding elder abuse. Grounded Theory proceedings were used for the analysis.
      RESULTS: Elder abuse is a naturalized practice, from HCP and elderly people's
      point of view; these perceptions are showed in different ways. CONCLUSION:
      Institutionalization, historical professionalization and lack of consciousness
      about needs of the elderly (sociocultural and economic), require changes in
      planning, organization and monitoring process in the Health System; training and
      educational interventions on staff and exchange attitudes and behavior are
      necessary in order to offer a health care that is comprehensive, decent, human
      and with respect for the human rights.

PMID- 25604414
TI  - [Potential hazard of zoonotic parasites present in canine feces in Puerto
      Escondido, Oaxaca].
AB  - OBJECTIVE: To estimate the zoonotic parasites prevalence in feral dog feces in
      Puerto Escondido. MATERIAL AND METHODS: The fecalism frecuency was estimated in
      ten zones. To identify the parasites parasitological flotation and direct smear
      methods were used. The parasitic prevalence was estimated in the canine feces.
      RESULTS: All the zones presented canine fecalism. The parasitic prevalence in the
      feces was 73.33%. The parasites with the highest prevalence were Toxocara canis
      (47.78%), Ancylostoma caninum (17.88%), and Dipylidium caninum (13.89%).
      CONCLUSION: Canine fecalism comes from strayed and owned dogs. 66.66% of the
      parasites found in the dog feces are zoonotics. The factors associated to this
      problem are the suburban habitat, waste mishandling and nil tenure of stray dogs.

PMID- 25604416
TI  - [Sexual debut in Mexico: a comparison of household national surveys].
AB  - OBJECTIVE: To estimate calendar of sexual debut in Mexico and its trends using
      national representative household surveys. MATERIALS AND METHODS: Analysis of
      five birth cohorts extracted from four national population based household
      surveys in Mexico (National Health Survey 2000, National Survey on Demographic
      Dynamics 2009, National Youth Survey 2010, and National Health & Nutrition Survey
      2012), using as outcome the proportion of individuals that reported sexual debut
      before the age of 16 and before the age of 20. RESULTS: Overall, the four
      analyzed surveys produce consistent results, although some differences were
      found. While a larger proportion among younger cohorts reported sexual debut
      before the age of 20, that was not the case for sexual debut before 16 years.
      CONCLUSIONS: While data seems to reflect a relative stable age of sexual debut in
      Mexico, there is a recent trend to prepone sexual initiation that highlights the
      need to strengthen comprehensive sexual education and the supply of sexual &
      reproductive health services that are accessible and friendly to adolescents thus
      responding to the growing demand from this age group.

PMID- 25604417
TI  - [Eating in a time of "crisis": new health and dietary contexts in Spain].
AB  - This article analyzes the reasons why food insecurity in Spain must increasingly
      be understood as lack of access to sufficient food resources to guarantee the
      survival and wellbeing of part of the population. Using data collected in an
      ongoing research project, two possible causes for this are explored. First, it is
      argued that certain positive developments that seemed firmly established, such as
      recognition of the right to an adequate diet and the leveling out of social
      differences in food consumption, are now being reversed by the current economic
      crisis. Second, the analysis focuses on strategies people in precarious
      circumstances use to obtain food, their relationship to health, and the need to
      take social inequality into consideration as an explanatory variable in
      accounting for different ways of procuring daily sustenance. 

PMID- 25604419
TI  - [School of Public Health of Mexico: educational and technological innovation in
      the new millennium].
AB  - This article was conceived to analyze the work of the School of Public Health of
      Mexico (ESPM for is acronym in Spanish) from the year 2000 to the present day.
      One of the highlights that we will examine is the reorientation of the
      educational work of the school in order to meet the challenges in health and
      education that emerged during the end of the twentieth century. In order to
      explain the evolution of this process, we will describe the three main guiding
      principles that characterize the present work of the school: the pedagogical
      model's change, the incorporation of the information and communication
      technologies, and the professionalization in teaching. The purpose of this work
      is to define those guiding principles, and to expose, through the contrast
      between past and present, the complete history of uninterrupted work of the
      School of Public Health of Mexico during its ninety-two years of existence, that
      has gone beyond the boundaries of the country. 

PMID- 25604418
TI  - [Listeriosis in Mexico: Clinical and epidemiological importance].
AB  - Listeriosis is caused by Listeria monocytogenes, an important food-borne disease
      due to its clinical forms, high mortality rate, and the economic impact in both
      clinical and food production industries. In Mexico, the lack of epidemiological
      surveillance systems leads to the need of accurate data on the incidence of
      listeriosis and its association with food-borne disease. In this paper, we
      present data about the presence of this bacterium in food, reports related to
      clinical cases of listeriosis, and information of diseases in which L.
      monocytogenes may be involved. However, in most of these cases the etiology was
      not established. Given this, there's a need to inform and warn the appropriate
      entities, to define strategies for the mandatory search of L. monocytogenes
      through the whole food production chain and clinical suspects, for the
      epidemiological importance and control of listeriosis in Mexico. 

PMID- 25604421
TI  - Electroconvulsive shocks decrease alpha2-adrenoceptor binding in the Flinders rat
      model of depression.
AB  - Despite years of drug development, electroconvulsive therapy (ECT) remains the
      most effective treatment for severe depression. The exact therapeutic mechanism
      of action of ECT is still unresolved and therefore we tested the hypothesis that
      the beneficial effect of ECT could in part be the result of increased
      noradrenergic neurotransmission leading to a decrease in alpha2-adrenoceptor
      binding. We have previously shown that both the Flinders sensitive line (FSL) and
      Flinders resistant line (FRL) rats had altered alpha2-adrenoceptor binding
      compared to control Sprague-Dawley (SD) rats. In this study, we treated female
      FSL, FRL and SD rats with electroconvulsive shock (ECS), an animal model of ECT,
      or sham stimulation for 10 days before brains were removed and cut into 20um
      thick sections. Densities of alpha2-adrenoceptors were measured by quantitative
      autoradiography in the hippocampus, thalamic nucleus, hypothalamus, amygdala,
      frontal cortex, insular cortex, and perirhinal cortex using the alpha2
      adrenoceptor antagonist, [(3)H]RX 821002. ECS decreased the binding of alpha2
      adrenoceptors in cortical regions in the FSL and cortical and amygdaloid regions
      in the control FRL rats compared to their respective sham treated group. The
      normal SD controls showed no significant response to ECS treatment. Our data
      suggest that the therapeutic effect of ECS may be mediated through a decrease of
      alpha2-adrenoceptors, probably due to a sustained increase in noradrenaline
      release. These data confirm the importance of the noradrenergic system and the
      alpha2-adrenoceptor in depression and in the mechanism of antidepressant
      treatments.

PMID- 25604422
TI  - Social visual contact, a primary "drive" for social animals?
AB  - Social animals are always searching for conspecifics, thereby expressing a
      genuine "social need". This need is illustrated by the fact that social isolation
      can induce isolation syndromes that can be attenuated by devices such as mirrors.
      Social contacts appear to be so vital for social animals that they may be ready
      to work to obtain social stimulations. We used operant conditioning to
      investigate the possibility to use visual contact (through pictures of
      conspecifics) as a primary reinforcer. Isolated European starlings (Sturnus
      vulgaris) were offered the choice of seeing either social images (i.e. pictures
      of conspecifics) or non-social images (i.e. pictures of landscapes or pictures of
      monkeys) by triggering sensors. In contrast with most studies, our subjects were
      presented still pictures of conspecifics and not videos. Moreover, these pictures
      were used as primary reinforcers and thus were not paired with food. Our data
      show that starlings were ready to work and to use the apparatus (i.e. sensors) to
      see pictures in the absence of any other reward. Moreover, they actively and
      significantly preferred pictures of conspecifics to pictures of inanimate objects
      (landscapes) or of heterospecifics (monkeys). This suggests that 2D pictures with
      a social overtone can be used as primary reinforcers for isolated social birds.

PMID- 25604424
TI  - Anomalous magnetoresistance in nanocrystalline gadolinium at low temperatures.
AB  - The results of a detailed investigation of electrical resistivity, rho(T) and
      transverse magnetoresistance (MR) in nanocrystalline Gd samples with an average
      grain size d = 12 nm and 18 nm reveal the following. Besides a major contribution
      to the residual resistivity, rho(r)(0), arising from the scattering of conduction
      electrons from grain surfaces/interfaces/boundaries (which increases drastically
      as the average grain size decreases, as expected), coherent electron-magnon
      scattering makes a small contribution to rho(r)(0), which gets progressively
      suppressed as the applied magnetic field (H) increases in strength. At low
      temperatures (T ? 40 K) and fields (H = 0 and H = 5 kOe), rho(H)(T) varies as
      T(3/2) with a change in slope at T(+) ? 16.5 K. As the field increases beyond 5
      kOe, the T(3/2) variation of rho(H)(T) at low temperatures (T ? 40 K) changes
      over to the T(2) variation and a slight change in the slope drho(H)/dT(2) at
      T(+)(H) disappears at H ? 20 kOe. The electron-electron scattering (Fermi liquid)
      contribution to the T(2) term, if present, is completely swamped by the coherent
      electron-magnon scattering contribution. As a function of temperature, (negative)
      MR goes through a dip at a temperature Tmin ? T(+), which increases with H as
      H(2/3). MR at Tmin also increases in magnitude with H and attains a value as
      large as ~15% (17%) for d = 12 nm (18 nm) at H = 90 kOe. This value is roughly
      five times greater than that reported earlier for crystalline Gd at Tmin ? 100 K.
      Unusually large MR results from an anomalous softening of magnon modes at T ?
      Tmin ~ 20 K. In the light of our previous magnetization and specific heat
      results, we show that all the above observations, including the H(2/3) dependence
      of Tmin (with Tmin(H) identified as the Bose-Einstein condensation (BEC)
      transition temperature, TBEC(H)), are the manifestations of the BEC of magnons at
      temperatures T ? TBEC. Contrasted with crystalline Gd, which behaves as a three
      dimensional (3D) pure uniaxial dipolar ferromagnet in the asymptotic critical
      region, rho(H=0)(T) of nanocrystalline Gd, in the critical region near the
      ferromagnetic-paramagnetic phase transition, is better described by the model
      proposed for a 3D random uniaxial dipolar ferromagnet.

PMID- 25604423
TI  - Non-adjacent visual dependency learning in chimpanzees.
AB  - Humans have a strong proclivity for structuring and patterning stimuli: Whether
      in space or time, we tend to mentally order stimuli in our environment and
      organize them into units with specific types of relationships. A crucial
      prerequisite for such organization is the cognitive ability to discern and
      process regularities among multiple stimuli. To investigate the evolutionary
      roots of this cognitive capacity, we tested chimpanzees-which, along with
      bonobos, are our closest living relatives-for simple, variable distance
      dependency processing in visual patterns. We trained chimpanzees to identify
      pairs of shapes either linked by an arbitrary learned association (arbitrary
      associative dependency) or a shared feature (same shape, feature-based
      dependency), and to recognize strings where items related to either of these ways
      occupied the first (leftmost) and the last (rightmost) item of the stimulus. We
      then probed the degree to which subjects generalized this pattern to new colors,
      shapes, and numbers of interspersed items. We found that chimpanzees can learn
      and generalize both types of dependency rules, indicating that the ability to
      encode both feature-based and arbitrary associative regularities over variable
      distances in the visual domain is not a human prerogative. Our results strongly
      suggest that these core components of human structural processing were already
      present in our last common ancestor with chimpanzees. 

PMID- 25604425
TI  - Specific insulin/IGF1 hybrid receptor activation assay reveals IGF1 as a more
      potent ligand than insulin.
AB  - This novel method enables specific measurement of the activation of hybrid
      receptors formed between the Insulin Receptor (IR) and the Insulin-like Growth
      Factor 1 Receptor (IGF1R). These hybrid receptors are present in tissues and cell
      lines expressing both IR and IGF1R. It is therefore challenging to separate the
      homodimer and hybrid receptor activation properties. This ELISA method enabled
      fast and quantitative measurements of activated hybrid receptors. The hybrid
      receptor specificity is obtained from a combination of two specific antibodies
      for IGF1R and for an IR tyrosine phosphorylation site. The specificity was shown
      by immunoprecipitations and Western blot analysis. IR exists as two splice
      variants; consequently, two splice variants of hybrid receptors can be expressed.
      It is reported here that both splice variants of insulin/IGF1 receptor hybrids
      are activated by IGF1 with >20-fold higher potency than insulin. 

PMID- 25604426
TI  - The lack of type I interferon induces neutrophil-mediated pre-metastatic niche
      formation in the mouse lung.
AB  - Metastases are the major cause of death from cancer. Thus, understanding the
      regulation of metastatic processes is of utmost importance. Here we show that
      mice with impaired type I IFN signaling (Ifnar1(-/-)) develop more lung
      metastases in the 4T1 mammary and LLC lung carcinoma model, compared to control
      mice. In Ifnar1(-/-) mice, higher metastasis load is accompanied by massive
      neutrophil accumulation in lungs. Elevated G-CSF levels in serum and enhanced
      CXCR2 expression on neutrophils are most likely responsible for this phenomenon.
      Lung infiltrating neutrophils facilitate an improved pre-metastatic niche
      formation, supporting more efficient tumor cell extravasation and proliferation
      in this organ. This is due to the enhanced expression of pro-metastatic proteins,
      like Bv8, MMP9, S100A8 and S100A9. Development of pre-metastatic niche together
      with reduced neutrophil cytotoxicity against tumor cells results in enhanced
      metastatic processes in Ifnar1(-/-) mice. Overall, our findings describe a novel
      role for IFN during metastasis development and suggest that new treatment
      strategies should be considered for prevention of metastasis formation in
      patients.

PMID- 25604427
TI  - Impact of a behaviour change intervention on long-lasting insecticidal net care
      and repair behaviour and net condition in Nasarawa State, Nigeria.
AB  - BACKGROUND: While some data on net durability have been accumulating in recent
      years, including formative qualitative research on attitudes towards net care and
      repair, no data are available on how the durability of a net is influenced by
      behaviour of net maintenance, care and repair, and whether behavioural change
      interventions (BCC) could substantially impact on the average useful life of the
      net. METHODS: The study used an intervention-control design with before-after
      assessment through repeated cross-sectional household surveys with two-stage
      cluster sampling following Nasarawa State's December 2010 mass campaign. All
      campaign nets were 100-denier polyester, long-lasting insecticidal nets (LLIN).
      Baseline, midline, and endline surveys occurred at one-year intervals, in March
      2012, March 2013, and April 2014, respectively. Outcome measures were the
      proportion of confirmed campaign nets with observed repairs, and the proportion
      in serviceable condition, measured with proportionate hole index (pHI) and
      according to WHO guidelines. RESULTS: For all respondents, exposure to BCC
      messages was strongly correlated with increased positive attitude towards care
      and repair, and increases in attitude were positively correlated with observed
      net repairs, and with the proportion of nets in serviceable condition. In a
      multivariate regression model, positive care and repair attitude (OR 6.17 p =
      0.001) and level of exposure (1 source: OR 4.00 p = 0.000; 3 sources: OR 9.34 p =
      0.000) remained the most significant predictors of net condition, controlling for
      background and environmental factors. Nets that were tied up had 2.70 higher odds
      of being in serviceable condition (p = 0.001), while repairs made to nets were
      not sufficient to improve their pHI category. Estimated median net lifespan was
      approximately one full year longer for nets in households with a positive
      compared to a negative attitude. CONCLUSION: Exposure to multiple channels of a
      comprehensive BCC intervention was associated with improved attitude scores, and
      with improved net condition at endline. It is possible for BCC interventions to
      change both attitudes and behaviours, and to have an important effect on overall
      median net lifespan. Care and repair messages are easily incorporated into
      existing malaria BCC platforms, and will help contribute to improved net
      condition, providing, in principle, more protection from malaria.

PMID- 25604430
TI  - The evaluation of distal symmetric polyneuropathy: utilisation and expenditures
      by community neurologists.

PMID- 25604431
TI  - Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and
      disease-modifying treatments.
AB  - Transthyretin (ATTR) amyloidosis is a life-threatening, gain-of-toxic-function
      disease characterised by extracellular deposition of amyloid fibrils composed of
      transthyretin (TTR). TTR protein destabilised by TTR gene mutation is prone to
      dissociate from its native tetramer to monomer, and to then misfold and aggregate
      into amyloid fibrils, resulting in autosomal dominant hereditary amyloidosis,
      including familial amyloid polyneuropathy, familial amyloid cardiomyopathy and
      familial leptomeningeal amyloidosis. Analogous misfolding of wild-type TTR
      results in senile systemic amyloidosis, now termed wild-type ATTR amyloidosis,
      characterised by acquired amyloid disease in the elderly. With the availability
      of genetic, biochemical and immunohistochemical diagnostic tests, patients with
      ATTR amyloidosis have been found in many nations; however, misdiagnosis is still
      common and considerable time is required before correct diagnosis in many cases.
      The current standard first-line treatment for hereditary ATTR amyloidosis is
      liver transplantation, which allows suppression of the main source of variant
      TTR. However, large numbers of patients are not suitable transplant candidates.
      Recently, the clinical effects of TTR tetramer stabilisers, diflunisal and
      tafamidis, were demonstrated in randomised clinical trials, and tafamidis has
      been approved for treatment of hereditary ATTR amyloidosis in European countries
      and in Japan. Moreover, antisense oligonucleotides and small interfering RNAs for
      suppression of variant and wild-type TTR synthesis are promising therapeutic
      approaches to ameliorate ATTR amyloidosis and are currently in phase III clinical
      trials. These newly developed therapies are expected to be effective for not only
      hereditary ATTR amyloidosis but also wild-type ATTR amyloidosis. 

PMID- 25604429
TI  - Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling,
      and Mechanotransduction in Mouse Articular Cartilage.
AB  - OBJECTIVE: Mechanical factors play a critical role in the physiology and
      pathology of articular cartilage, although the mechanisms of mechanical signal
      transduction are not fully understood. We undertook this study to test the
      hypothesis that type VI collagen is necessary for mechanotransduction in
      articular cartilage by determining the effects of type VI collagen knockout on
      the activation of the mechano-osmosensitive, calcium-permeable channel TRPV4
      (transient receptor potential vanilloid channel 4) as well as on osmotically
      induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties.
      METHODS: Confocal laser scanning microscopy was used to image TRPV4-mediated
      calcium signaling and osmotically induced cell swelling in intact femora from 2-
      and 9-month-old wild-type (WT) and type VI collagen-deficient (Col6a1(-/-)) mice.
      Immunofluorescence-guided atomic force microscopy was used to map PCM mechanical
      properties based on the presence of perlecan. RESULTS: Hypo-osmotic stress
      induced TRPV4-mediated calcium signaling was increased in Col6a1(-/-) mice
      relative to WT controls at 2 months. Col6a1(-/-) mice exhibited significantly
      increased osmotically induced cell swelling and decreased PCM moduli relative to
      WT controls at both ages. CONCLUSION: In contrast to our original hypothesis,
      type VI collagen was not required for TRPV4-mediated Ca(2+) signaling; however,
      knockout of type VI collagen altered the mechanical properties of the PCM, which
      in turn increased the extent of cell swelling and osmotically induced TRPV4
      signaling in an age-dependent manner. These findings emphasize the role of the
      PCM as a transducer of mechanical and physicochemical signals, and they suggest
      that alterations in PCM properties, as may occur with aging or osteoarthritis,
      can influence mechanotransduction via TRPV4 or other ion channels.

PMID- 25604428
TI  - Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders:
      genetic and environmental factors involved in type A MAO expression.
AB  - Monoamine oxidase types A and B (MAO-A, MAO-B) regulate the levels of monoamine
      neurotransmitters in the brain, and their dysfunction may be involved in the
      pathogenesis and influence the clinical phenotypes of neuropsychiatric disorders.
      Reversible MAO-A inhibitors, such as moclobemide and befloxatone, are currently
      employed in the treatment of emotional disorders by inhibiting the enzymatic
      degradation of dopamine, serotonin and norepinephrine in the central nervous
      system (CNS). It has been suggested that the irreversible MAO-B inhibitors
      selegiline and rasagiline exert a neuroprotective effect in Parkinson's and
      Alzheimer's diseases. This effect, however, is not related to their inhibition of
      MAO activity; in animal and cellular models, selegiline and rasagiline protect
      neuronal cells through their anti-apoptotic activity and induction of pro
      survival genes. There is increasing evidence that MAO-A activity, but not that of
      MAO-B, is implicated in the pathophysiology of neurodegenerative disorders, but
      also in gene induction by MAO-B inhibitors; on the other hand, selegiline and
      rasagiline increase MAO-A mRNA, protein, and enzyme activity levels. Taken
      together, these results suggest that each MAO subtype exerts effects that
      modulate the expression and activity of the other isoenzyme. The roles of MAO-A
      and -B in the CNS should therefore be re-evaluated with respect to the "type
      specificity" of their inhibitors, which may not be unconditional during chronic
      treatment. Mao-a expression, in particular, may be implicated in pathogenesis and
      phenotypes in neuropsychiatric disorders. MAO-A expression is modified by mao
      polymorphisms affecting its transcriptional efficiency, as well as by mutations
      and polymorphism of parkin, Sirt1, FOXO, microRNA, presenilin-1, and other
      regulatory proteins. In addition, childhood maltreatment has been shown to have
      an impact upon adolescent social behavior in children with mao-a polymorphisms of
      low transcriptional activity. Low MAO-A activity may increase the levels of
      serotonin and norepinephrine, resulting in disturbed neurotransmitter system
      development and behavior. This review discusses genetic and environmental factors
      involved in the regulation of MAO-A expression, in the contexts of
      neuropsychiatric function and of the regulation of neuronal survival and death. 

PMID- 25604432
TI  - Disialoganglioside GD2 as a therapeutic target for human diseases.
AB  - INTRODUCTION: Ganglioside GD2 is found in vertebrates and invertebrates,
      overexpressed among pediatric and adult solid tumors, including neuroblastoma,
      glioma, retinoblastoma, Ewing's family of tumors, rhabdomyosarcoma, osteosarcoma,
      leiomyosarcoma, liposarcoma, fibrosarcoma, small cell lung cancer and melanoma.
      It is also found on stem cells, neurons, some nerve fibers and basal layer of the
      skin. AREAS COVERED: GD2 provides a promising clinical target for radiolabeled
      antibodies, bispecific antibodies, chimeric antigen receptor (CAR)-modified T
      cells, drug conjugates, nanoparticles and vaccines. Here, we review its
      biochemistry, normal physiology, role in tumorigenesis, important characteristics
      as a target, as well as anti-GD2-targeted strategies. EXPERT OPINION: Bridging
      the knowledge gaps in understanding the interactions of GD2 with signaling
      molecules within the glycosynapses, and the regulation of its cellular expression
      should improve therapeutic strategies targeting this ganglioside. In addition to
      anti-GD2 IgG mAbs, their drug conjugates, radiolabeled forms especially when
      genetically engineered to improve therapeutic index and novel bispecific forms or
      CARs to retarget T-cells are promising candidates for treating metastatic
      cancers.

PMID- 25604433
TI  - Information Seeking in Social Media: A Review of YouTube for Sedentary Behavior
      Content.
AB  - BACKGROUND: The global prevalence of sedentary lifestyles is of grave concern for
      public health around the world. Moreover, the health risk of sedentary behaviors
      is of growing interest for researchers, clinicians, and the general public as
      evidence demonstrates that prolonged amounts of sedentary time increases risk for
      lifestyle-related diseases. There is a growing trend in the literature that
      reports how social media can facilitate knowledge sharing and collaboration.
      Social sites like YouTube facilitate the sharing of media content between users.
      OBJECTIVE: The purpose of this project was to identify sedentary behavior content
      on YouTube and describe features of this content that may impact the
      effectiveness of YouTube for knowledge translation. METHODS: YouTube was searched
      on a single day by 3 independent reviewers for evidence-based sedentary behavior
      content. Subjective data (eg, video purpose, source, and activity type portrayed)
      and objective data (eg, number of views, comments, shares, and length of the
      video) were collected from video. RESULTS: In total, 106 videos met inclusion
      criteria. Videos were uploaded from 13 countries around the globe (ie, Australia,
      Barbados, Belgium, Canada, Colombia, Kenya, New Zealand, Russia, South Africa,
      Spain, Ukraine, United Kingdom, United States). The median video length was 3:00
      minutes: interquartile range (IQR) 1:44-5:40. On average, videos had been on
      YouTube for 15.0 months (IQR 6.0-27.5) and had been viewed 239.0 times (IQR 44.5
      917.5). Videos had remarkably low numbers of shares (median 0) and comments
      (median 1). Only 37.7% (40/106) of videos portrayed content on sedentary
      behaviors, while the remaining 66 videos portrayed physical activity or a mix of
      behaviors. Academic/health organizations (39.6%, 42/106) and individuals (38.7%,
      41/106) were the most prevalent source of videos, and most videos (67.0%, 71/106)
      aimed to educate viewers about the topic. CONCLUSIONS: This study explored
      sedentary behavior content available on YouTube. Findings demonstrate that there
      is confusion between physical activity and sedentary behaviors, that content is
      being uploaded to the site from around the globe, that content is primarily from
      health organizations and individuals with the purpose of educating fellow users,
      but that low views, comments, and shares suggest that sedentary behavior content
      is relatively underutilized on YouTube. Future research may wish to leverage
      social platforms, such as YouTube, to facilitate implementation and sharing of
      evidence-based sedentary behavior content.

PMID- 25604434
TI  - [Individual in-patient and out-patient prevention in occupational skin diseases].
AB  - Concerning all occupation-related diseases, one-third of those reported in
      Germany are skin diseases. Among them, contact dermatitis is the most frequent
      skin disease. It usually presents as hand eczema leading to a loss of function
      and ability to work as well as reduced quality of life. Due to the high demand a
      number of prevention programmes were introduced. They comprise measures of
      secondary (out-patient) and tertiary (in-patient) prevention. Out-patient
      prevention measures include dermatologist's report and occupation-tailored
      teaching and prevention programmes. If the occupational skin disease is severe,
      therapy is not successful or the diagnosis is not clear measures of tertiary
      prevention can be offered as an in-patient treatment and prevention programme.
      All this aims to prevent the job loss of the patient. Preventive measures in
      occupational dermatology have proven to be very effective in recent years,
      especially measures of individual in-patient and out-patient prevention as
      components of a complex hierarchical prevention concept. This integrated concept
      of an in-patient/out-patient disease management reveals remarkable pertinent
      effectivity for patients with severe occupational dermatoses in risk professions.

PMID- 25604435
TI  - [Quality management in occupational dermatology].
AB  - BACKGROUND: Health care of patients with occupational dermatitis (OD) in the
      sense of suspected "BK 5101" is carried out in Germany within the optimized
      dermatologist's procedure and the "dermal intervention" (formerly: hierarchical
      multistep intervention approach) of the statutory accident insurance (UVT),
      respectively. OBJECTIVES AND METHODS: Dermatologists and UVT administrators are
      obliged to improve OD patient care by continuous quality management measures.
      Essential quality management elements include the research projects EVA_Haut and
      VVH, the clearing procedure of the Task Force on Occupational and Environmental
      Dermatology (ABD), training of dermatologists to receive the CME certificate
      "Occupational Dermatology (ABD)", the establishment of processing standards for
      administrators and optimized dermatologist's report forms (based on the results
      of all the above steps taken). RESULTS: It was shown that the optimized
      dermatologist's procedure and "dermal intervention" are established in Germany.
      Also, the available preventive and therapeutic measures for OD patients are
      effective. Despite the increase of cases with suspected OD, the number of cases
      in which a career change was required is almost constant (3 %); at the same time
      the percentage of notified cases which, as a result, are covered within the
      dermatologist's procedure by the UVT is rising (86 %). The measures recently
      taken have continuously increased quality of health care in occupational
      dermatology.

PMID- 25604436
TI  - A multicomponent T2 relaxometry algorithm for myelin water imaging of the brain.
AB  - PURPOSE: Models based on a sum of damped exponentials occur in many applications,
      particularly in multicomponent T2 relaxometry. The problem of estimating the
      relaxation parameters and the corresponding amplitudes is known to be difficult,
      especially as the number of components increases. In this article, the commonly
      used non-negative least squares spectrum approach is compared to a recently
      published estimation algorithm abbreviated as Exponential Analysis via System
      Identification using Steiglitz-McBride. METHODS: The two algorithms are evaluated
      via simulation, and their performance is compared to a statistical benchmark on
      precision given by the Cramer-Rao bound. By applying the algorithms to an in vivo
      brain multi-echo spin-echo dataset, containing 32 images, estimates of the myelin
      water fraction are computed. RESULTS: Exponential Analysis via System
      Identification using Steiglitz-McBride is shown to have superior performance when
      applied to simulated T2 relaxation data. For the in vivo brain, Exponential
      Analysis via System Identification using Steiglitz-McBride gives an myelin water
      fraction map with a more concentrated distribution of myelin water and less
      noise, compared to non-negative least squares. CONCLUSION: The Exponential
      Analysis via System Identification using Steiglitz-McBride algorithm provides an
      efficient and user-parameter-free alternative to non-negative least squares for
      estimating the parameters of multiple relaxation components and gives a new way
      of estimating the spatial variations of myelin in the brain.

PMID- 25604437
TI  - Interfacial biomimetic synthesis of silica nanocapsules using a recombinant
      catalytic modular protein.
AB  - This paper reports interfacially driven synthesis of oil-core silica-shell
      nanocapsules using a rationally designed recombinant catalytic modular protein
      (ReCaMoP), in lieu of a conventional chemical surfactant. A 116-residue protein,
      D4S2, was designed by modularizing a surface-active protein module having four
      helix bundle structure in bulk and a biosilicification-active peptide module rich
      in cationic residues. This modular combination design allowed the protein to be
      produced via the industrially relevant cell factory Escherichia coli with
      simplified purification conferred by thermostability engineered in design.
      Dynamic interfacial tension and thin film pressure balance were used to gain an
      overview of the protein behavior at macroscopic interfaces. Functionalities of
      D4S2 to make silica nanocapsules were demonstrated by facilitating formation and
      stabilization of pharmaceutically grade oil droplets through its surface-active
      module and then by directing nucleation and growth of a silica shell at the oil
      water interface through its biosilicification-active module. Through these
      synergistic activities in D4S2, silica nanocapsules could be formed at near
      neutral pH and ambient temperature without using any organic solvents that might
      have negative environmental and sustainability impacts. This work introduces
      parallelization of biomolecular, scale-up and interfacial catalytic design
      strategies for the ultimate development of sustainable and scalable production of
      a recombinant modular protein that is able to catalyze synthesis of oil-filled
      silica nanocapsules under environmentally friendly conditions, suitable for use
      as controlled-release nanocarriers of various actives in biomedical and
      agricultural applications. 

PMID- 25604439
TI  - Gene delivery of suppressors of cytokine signaling (SOCS) inhibits inflammation
      and atherosclerosis development in mice.
AB  - Chronic activation of Janus kinase/signal transducers and activators of
      transcription (JAK/STAT) pathway contributes to vascular inflammation and
      atherosclerosis by inducing expression of genes involved in cell proliferation,
      differentiation and migration. We aimed to investigate whether enforced
      expression of negative regulators, the suppressors of cytokine signaling (SOCS1
      and SOCS3), inhibits harmful JAK/STAT-mediated responses and affects
      atherosclerosis in apolipoprotein E knockout mice. Adenovirus-mediated SOCS1
      transgene expression impaired the onset and progression of atherosclerosis
      without impact on lipid profile, whereas SOCS3 was only effective on early
      atherosclerosis. Mechanistically, SOCS gene delivery, primarily SOCS1, attenuated
      STAT1 and STAT3 activation and reduced the expression of STAT-dependent genes
      (chemokine/chemokine receptors, adhesion molecules, pro-inflammatory cytokines
      and scavenger receptors) in aortic tissue. Furthermore, atherosclerotic plaques
      exhibit a more stable phenotype characterized by lower lipids, T cells and M1
      macrophages and higher M2 macrophages and collagen. Atheroprotection was
      accompanied by a systemic alteration of T helper- and T regulatory-related genes
      and a reduced activation state of circulating monocytes. In vascular smooth
      muscle cells and macrophages, SOCS gene delivery inhibited cytokine-induced STAT
      activation, pro-inflammatory gene expression, cell migration and proliferation.
      In conclusion, targeting SOCS proteins, predominantly SOCS1, to suppress
      pathological mechanisms involved in atheroma plaque progression and
      destabilization could be an interesting anti-atherosclerotic strategy. 

PMID- 25604440
TI  - Standing gold nanorod arrays as reproducible SERS substrates for measurement of
      pesticides in apple juice and vegetables.
AB  - There is an increasing interest in recent years in using novel nanomaterials as
      cost-effective, sensitive, and reproducible substrate for surface-enhanced Raman
      spectroscopy (SERS) applications. In this study, a novel SERS substrate was
      developed by assembling gold nanorods into standing arrays on a gold-coated
      silicon slide. The standing nanorod arrays were closely packed on the gold film,
      generating strong electromagnetic field and uniformly distributed SERS "hot
      spots" on the array surface. The as-prepared SERS substrates were used to detect
      a widely used pesticide (that is, carbaryl) in acetonitrile-water solution, apple
      juice, and cabbage. Results demonstrate that the actual concentrations of
      carbaryl in apple juice and cabbage were linearly correlated with the
      concentrations predicted by the multiple linear regression models (R > 0.97). The
      detection limits of carbaryl in apple juice and cabbage were both 2.5 ppm,
      meeting the maximum residue limits set by US Environmental Protection Agency
      (EPA). SERS can detect as low as 0.1 ppm of carbaryl in acetonitrile-water
      solution. In addition, satisfactory recoveries were obtained for carbaryl in both
      apple juice and cabbage. These results indicate that SERS coupled with the
      standing gold nanorod array substrates is a sensitive and reproducible method and
      can accurately detect pesticides in foods. 

PMID- 25604441
TI  - Changes in thyroid function with age: results from the Pizarra population-based
      longitudinal study.
AB  - BACKGROUND: Results of studies examining the influence of age on thyroid function
      and TSH levels, in the absence of thyroid disease, remain controversial. The aim
      of this study was to determine the course of thyroid function over 11 years in a
      population with normal thyroid function. METHODS: This is a population-based
      prospective study started in 1995-1997 (first phase), and reassessed 6 (second
      phase) and 11 years later (third phase). RESULTS: The TSH and FT4 in the third
      phase were significantly increased (p=0.001 and p=0.001, respectively), with the
      values being higher particularly from the age of 50 years. In those persons with
      a baseline TSH>=1.2 and <3 MUIU/mL, the OR of having a TSH of 3-5 MUIU/mL in the
      third phase was 6.10 (p=0.004). In those with a baseline TSH>=3 and <=5 MUIU/mL,
      the OR of having a TSH of 3-5 MUIU/mL in the third phase was 20.8 (p<0.0001).
      Similar results were found for FT4. CONCLUSION: In a population free of clinical
      thyroid disease, TSH and FT4 values rise over the years. This increase occurs in
      all age groups, but depends mainly on the basal concentrations of TSH and FT4.

PMID- 25604442
TI  - The roles of ROS and ABA in systemic acquired acclimation.
AB  - Systemic responses to environmental stimuli are essential for the survival of
      multicellular organisms. In plants, they are initiated in response to many
      different signals including pathogens, wounding, and abiotic stresses. Recent
      studies highlighted the importance of systemic acquired acclimation to abiotic
      stresses in plants and identified several different signals involved in this
      response. These included reactive oxygen species (ROS) and calcium waves,
      hydraulic waves, electric signals, and abscisic acid (ABA). Here, we address the
      interactions between ROS and ABA at the local and systemic tissues of plants
      subjected to abiotic stress and attempt to propose a model for the involvement of
      ROS, ABA, and stomata in systemic signaling leading to systemic acquired
      acclimation. 

PMID- 25604444
TI  - The PB1 domain in auxin response factor and Aux/IAA proteins: a versatile protein
      interaction module in the auxin response.
AB  - An integral part of auxin-regulated gene expression involves the interplay of two
      types of transcription factors, the DNA binding auxin response factor (ARF)
      activators and the interacting auxin/indole acetic acid (Aux/IAA) repressors.
      Insight into the mechanism of how these transcription factors interact with one
      another has recently been revealed from crystallographic information on ARF5 and
      ARF7 C-terminal domains (i.e., a protein-protein interaction domain referred to
      as domain III/IV that is related to domain III/IV in Aux/IAA proteins). Three
      dimensional structures showed that this domain in ARF5 and ARF7 conforms to a
      well-known PB1 (Phox and Bem1) domain that confers protein-protein interactions
      with other PB1 domain proteins through electrostatic contacts. Experiments
      verifying the importance of charged amino acids in conferring ARF and Aux/IAA
      interactions have confirmed the PB1 domain structure. Some in planta experiments
      designed to test the validity of PB1 interactions in the auxin response have led
      to updated models for auxin-regulated gene expression and raised many questions
      that will require further investigation. In addition to the PB1 domain, a second
      protein interaction module that functions in ARF-ARF dimerization and facilitates
      DNA binding has recently been revealed from crystallography studies on the ARF1
      and ARF5 DNA binding domains. 

PMID- 25604443
TI  - SCFTIR1/AFB-based auxin perception: mechanism and role in plant growth and
      development.
AB  - Auxin regulates a vast array of growth and developmental processes throughout the
      life cycle of plants. Auxin responses are highly context dependent and can
      involve changes in cell division, cell expansion, and cell fate. The complexity
      of the auxin response is illustrated by the recent finding that the auxin
      responsive gene set differs significantly between different cell types in the
      root. Auxin regulation of transcription involves a core pathway consisting of the
      TIR1/AFB F-box proteins, the Aux/IAA transcriptional repressors, and the ARF
      transcription factors. Auxin is perceived by a transient coreceptor complex
      consisting of a TIR1/AFB protein and an Aux/IAA protein. Auxin binding to the
      coreceptor results in degradation of the Aux/IAAs and derepression of ARF-based
      transcription. Although the basic outlines of this pathway are now well
      established, it remains unclear how specificity of the pathway is conferred.
      However, recent results, focusing on the ways that these three families of
      proteins interact, are starting to provide important clues. 

PMID- 25604446
TI  - The Plant Cell reviews dynamic aspects of plant hormone signaling and crosstalk.

PMID- 25604445
TI  - PIN-dependent auxin transport: action, regulation, and evolution.
AB  - Auxin participates in a multitude of developmental processes, as well as
      responses to environmental cues. Compared with other plant hormones, auxin
      exhibits a unique property, as it undergoes directional, cell-to-cell transport
      facilitated by plasma membrane-localized transport proteins. Among them, a
      prominent role has been ascribed to the PIN family of auxin efflux facilitators.
      PIN proteins direct polar auxin transport on account of their asymmetric
      subcellular localizations. In this review, we provide an overview of the multiple
      developmental roles of PIN proteins, including the atypical endoplasmic reticulum
      localized members of the family, and look at the family from an evolutionary
      perspective. Next, we cover the cell biological and molecular aspects of PIN
      function, in particular the establishment of their polar subcellular
      localization. Hormonal and environmental inputs into the regulation of PIN action
      are summarized as well. 

PMID- 25604448
TI  - Pocket depth and bleeding on probing and their associations with dental,
      lifestyle, socioeconomic and blood variables: a cross-sectional, multicenter
      feasibility study of the German National Cohort.
AB  - BACKGROUND: To investigate the periodontal disease status in a multi-center cross
      sectional study in Germany. Associations of dental, socio-economic, blood and
      biomedical variables with periodontal outcome parameters were evaluated. METHODS:
      From 4 different centers N = 311 persons were included, drawn randomly from the
      registration offices. Maximal pocket depth (PD) was used as primary indicator for
      periodontitis. It was classified as: no/mild <=3 mm, moderate 4-5 mm, severe >=6
      mm. Associations between socioeconomic (household income, education), lifestyle,
      and biomedical factors and PD or bleeding on probing (BOP) per site ("Yes"/"No")
      was analyzed with logistic regression analysis. RESULTS: Mean age of subjects was
      46.4 (range 20-77) years. A significantly higher risk of deeper pockets for
      smokers (OR = 2.4, current vs. never smoker) or persons with higher BMI (OR =
      1.6, BMI increase by 5) was found. Severity of periodontitis was significantly
      associated with caries lesions (p = 0.01), bridges (p < .0001), crowns (p <
      .0001), leukocytes (p = 0.04), HbA1c (p < .0001) and MCV (p = 0.04). PD was
      positively correlated with BOP. No significant associations with BOP were found
      in regression analysis. CONCLUSIONS: Earlier findings for BMI and smoking with
      severity of PD were confirmed. Dental variables might be influenced by potential
      confounding factors e.g. dental hygiene. For blood parameters interactions with
      unknown systemic diseases may exist.

PMID- 25604450
TI  - Joint modelling of repeated measurement and time-to-event data: an introductory
      tutorial.
AB  - BACKGOUND: The term 'joint modelling' is used in the statistical literature to
      refer to methods for simultaneously analysing longitudinal measurement outcomes,
      also called repeated measurement data, and time-to-event outcomes, also called
      survival data. A typical example from nephrology is a study in which the data
      from each participant consist of repeated estimated glomerular filtration rate
      (eGFR) measurements and time to initiation of renal replacement therapy (RRT).
      Joint models typically combine linear mixed effects models for repeated
      measurements and Cox models for censored survival outcomes. Our aim in this paper
      is to present an introductory tutorial on joint modelling methods, with a case
      study in nephrology. METHODS: We describe the development of the joint modelling
      framework and compare the results with those obtained by the more widely used
      approaches of conducting separate analyses of the repeated measurements and
      survival times based on a linear mixed effects model and a Cox model,
      respectively. Our case study concerns a data set from the Chronic Renal
      Insufficiency Standards Implementation Study (CRISIS). We also provide details of
      our open-source software implementation to allow others to replicate and/or
      modify our analysis. RESULTS: The results for the conventional linear mixed
      effects model and the longitudinal component of the joint models were found to be
      similar. However, there were considerable differences between the results for the
      Cox model with time-varying covariate and the time-to-event component of the
      joint model. For example, the relationship between kidney function as measured by
      eGFR and the hazard for initiation of RRT was significantly underestimated by the
      Cox model that treats eGFR as a time-varying covariate, because the Cox model
      does not take measurement error in eGFR into account. CONCLUSIONS: Joint models
      should be preferred for simultaneous analyses of repeated measurement and
      survival data, especially when the former is measured with error and the
      association between the underlying error-free measurement process and the hazard
      for survival is of scientific interest.

PMID- 25604447
TI  - The yin-yang of hormones: cytokinin and auxin interactions in plant development.
AB  - The phytohormones auxin and cytokinin interact to regulate many plant growth and
      developmental processes. Elements involved in the biosynthesis, inactivation,
      transport, perception, and signaling of these hormones have been elucidated,
      revealing the variety of mechanisms by which signal output from these pathways
      can be regulated. Recent studies shed light on how these hormones interact with
      each other to promote and maintain plant growth and development. In this review,
      we focus on the interaction of auxin and cytokinin in several developmental
      contexts, including its role in regulating apical meristems, the patterning of
      the root, the development of the gynoecium and female gametophyte, and
      organogenesis and phyllotaxy in the shoot. 

PMID- 25604449
TI  - Bias from conditioning on live birth in pregnancy cohorts: an illustration based
      on neurodevelopment in children after prenatal exposure to organic pollutants.
AB  - Only 60-70% of fertilized eggs may result in a live birth, and very early fetal
      loss mainly goes unnoticed. Outcomes that can only be ascertained in live-born
      children will be missing for those who do not survive till birth. In this
      article, we illustrate a common bias structure (leading to 'live-birth bias')
      that arises from studying the effects of prenatal exposure to environmental
      factors on long-term health outcomes among live births only in pregnancy cohorts.
      To illustrate this we used prenatal exposure to perfluoroalkyl substances (PFAS)
      and attention-deficit/hyperactivity disorder (ADHD) in school-aged children as an
      example. PFAS are persistent organic pollutants that may impact human fecundity
      and be toxic for neurodevelopment. We simulated several hypothetical scenarios
      based on characteristics from the Danish National Birth Cohort and found that a
      weak inverse association may appear even if PFAS do not cause ADHD but have a
      considerable effect on fetal survival. The magnitude of the negative bias was
      generally small, and adjusting for common causes of the outcome and fetal loss
      can reduce the bias. Our example highlights the need to identify the determinants
      of pregnancy loss and the importance of quantifying bias arising from
      conditioning on live birth in observational studies. 

PMID- 25604452
TI  - Genetic and environmental influences on adolescents' smoking involvement: a multi
      informant twin study.
AB  - Studying monozygotic and dizygotic adolescent twin pairs of both sexes reared
      together, the present study examined the extent to which the variance in smoking
      involvement is attributable to genetic and environmental effects, and to what
      extent there are sex differences in the etiology. Questionnaire data on how often
      the adolescent had ever smoked tobacco was collected from a population-based twin
      sample consisting of seven national birth cohorts (ages 12-18), their mothers,
      and their fathers (N = 1,394 families). The data was analyzed with multivariate
      genetic modeling, using a multi-informant design. The etiological structure of
      smoking involvement was best represented in an ACE common pathway model, with
      smoking defined as a latent factor loading onto all three informants' reports.
      Estimates could be set equal across sexes. Results showed that adolescent
      lifetime smoking involvement was moderately heritable (37 %). The largest
      influence was from the shared environment (56 %), while environmental effects
      unique to each twin had minimal influence (7 %).

PMID- 25604451
TI  - Genetic influences on response to novel objects and dimensions of personality in
      Papio baboons.
AB  - Behavioral variation within and between populations and species of the genus
      Papio has been studied extensively, but little is known about the genetic causes
      of individual- or population-level differences. This study investigates the
      influence of genetic variation on personality (sometimes referred to as
      temperament) in baboons and identifies a candidate gene partially responsible for
      the variation in that phenotype. To accomplish these goals, we examined
      individual variation in response to both novel objects and an apparent novel
      social partner (using a mirror test) among pedigreed baboons (n = 578) from the
      Southwest National Primate Research Center. We investigated the frequency and
      duration of individual behaviors in response to novel objects and used
      multivariate factor analysis to identify trait-like dimensions of personality.
      Exploratory factor analysis identified two distinct dimensions of personality
      within this population. Factor 1 accounts for 46.8 % of the variance within the
      behavioral matrix, and consists primarily of behaviors related to the "boldness"
      of the subject. Factor 2 accounts for 18.8 % of the variation, and contains
      several "anxiety" like behaviors. Several specific behaviors, and the two
      personality factors, were significantly heritable, with the factors showing
      higher heritability than most individual behaviors. Subsequent analyses show that
      the behavioral reactions observed in the test protocol are associated with
      animals' social behavior observed later in their home social groups. Finally we
      used linkage analysis to map quantitative trait loci for the measured phenotypes.
      Single nucleotide polymorphisms in a positional candidate gene (SNAP25) are
      associated with variation in one of the personality factors, and CSF levels of
      homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. This study documents
      heritable variation in personality among baboons and suggests that sequence
      variation in SNAP25 may influence differences in behavior and neurochemistry in
      these nonhuman primates.

PMID- 25604455
TI  - Hepatitis B surface antigen in late hepatitis B infection.
AB  - Hepatitis B surface antigen (HBsAg) levels are used to evaluate and monitor
      clinical phases of chronic hepatitis B infection but their clinical significance
      is unclear in the late complications, cirrhosis of the liver and hepatocellular
      carcinoma. This study aimed to evaluate HBsAg levels across the whole natural
      history of hepatitis B virus infection, including late complications. This
      retrospective, cross-sectional study enrolled 838 treatment-naive patients
      diagnosed with chronic hepatitis B infection at First Affiliated Hospital of
      Fujian Medical University between 2009 and 2012. Patients were classified into
      six groups: immunotolerance, immunoclearance, low replicative, negative hepatitis
      e (HBeAg) phases, liver cirrhosis, and hepatocellular carcinoma. Main outcome
      measures were serum HBsAg, HBeAg, HBV DNA, total bilirubin, albumin, alanine and
      aspartate aminotransferase, and quantitative correlation of HBsAg with HBV DNA.
      HBsAg levels declined significantly between clinical phases of infection (all P <
      0.001) and were significantly lower in decompensated than in compensated
      cirrhosis (2.90 vs. 3.30, P < 0.001) but not significantly different between
      early versus advanced hepatocellular carcinoma. Significant positive correlations
      were observed between serum HBsAg and HBV DNA at immunoclearance and HBeAg
      negative phases, compensated and decompensated liver cirrhosis and advanced but
      not early hepatocellular carcinoma (all P < 0.001). HBsAg and HBV DNA were
      significantly higher in HBeAg positive patients with advanced hepatocellular
      carcinoma (P < 0.001). HBsAg levels differ significantly between chronic
      hepatitis B infection phases, decreasing progressively from chronic infection to
      cirrhosis and hepatocellular carcinoma. Significant correlations are found
      between serum HBsAg and HBV DNA.

PMID- 25604453
TI  - Genome-wide identification and comparative analysis of the heat shock
      transcription factor family in Chinese white pear (Pyrus bretschneideri) and five
      other Rosaceae species.
AB  - BACKGROUND: Heat shock transcription factors (Hsfs), which act as important
      transcriptional regulatory proteins in eukaryotes, play a central role in
      controlling the expression of heat-responsive genes. At present, the genomes of
      Chinese white pear ('Dangshansuli') and five other Rosaceae fruit crops have been
      fully sequenced. However, information about the Hsfs gene family in these
      Rosaceae species is limited, and the evolutionary history of the Hsfs gene family
      also remains unresolved. RESULTS: In this study, 137 Hsf genes were identified
      from six Rosaceae species (Pyrus bretschneideri, Malus * domestica, Prunus
      persica, Fragaria vesca, Prunus mume, and Pyrus communis), 29 of which came from
      Chinese white pear, designated as PbHsf. Based on the structural characteristics
      and phylogenetic analysis of these sequences, the Hsf family genes could be
      classified into three main groups (classes A, B, and C). Segmental and dispersed
      duplications were the primary forces underlying Hsf gene family expansion in the
      Rosaceae. Most of the PbHsf duplicated gene pairs were dated back to the recent
      whole-genome duplication (WGD, 30-45 million years ago (MYA)). Purifying
      selection also played a critical role in the evolution of Hsf genes.
      Transcriptome data demonstrated that the expression levels of the PbHsf genes
      were widely different. Six PbHsf genes were upregulated in fruit under naturally
      increased temperature. CONCLUSION: A comprehensive analysis of Hsf genes was
      performed in six Rosaceae species, and 137 full length Hsf genes were identified.
      The results presented here will undoubtedly be useful for better understanding
      the complexity of the Hsf gene family and will facilitate functional
      characterization in future studies.

PMID- 25604454
TI  - Good practice characteristics of diet and physical activity interventions and
      policies: an umbrella review.
AB  - BACKGROUND: This umbrella review aimed at eliciting good practice characteristics
      of interventions and policies aiming at healthy diet, increasing physical
      activity, and lowering sedentary behaviors. Applying the World Health
      Organization's framework, we sought for 3 types of characteristics, reflecting:
      (1) main intervention/policy characteristics, referring to the design, targets,
      and participants, (2) monitoring and evaluation processes, and (3) implementation
      issues. This investigation was undertaken by the DEDPIAC Knowledge Hub (the
      Knowledge Hub on the DEterminants of DIet and Physical ACtivity), which is an
      action of the European Union's joint programming initiative. METHODS: A
      systematic review of reviews and stakeholder documents was conducted. Data from 7
      databases was analyzed (99 documents met inclusion criteria). Additionally,
      resources of 7 major stakeholders (e.g., World Health Organization) were
      systematically searched (10 documents met inclusion criteria). Overall, the
      review yielded 74 systematic reviews, 16 position review papers, and 19
      stakeholders' documents. Across characteristics, 25% were supported by >= 4
      systematic reviews. Further, 25% characteristics were supported by >= 3
      stakeholders' documents. If identified characteristics were included in at least
      4 systematic reviews or at least 3 stakeholders' documents, these good practice
      characteristics were classified as relevant. RESULTS: We derived a list of 149
      potential good practice characteristics, of which 53 were classified as relevant.
      The main characteristics of intervention/policy (n = 18) fell into 6 categories:
      the use of theory, participants, target behavior, content development/management,
      multidimensionality, practitioners/settings. Monitoring and evaluation
      characteristics (n = 18) were grouped into 6 categories: costs/funding, outcomes,
      evaluation of effects, time/effect size, reach, the evaluation of participation
      and generalizability, active components/underlying processes. Implementation
      characteristics (n = 17) were grouped into eight categories: participation
      processes, training for practitioners, the use/integration of existing resources,
      feasibility, maintenance/sustainability, implementation partnerships,
      implementation consistency/adaptation processes, transferability. CONCLUSIONS:
      The use of the proposed list of 53 good practice characteristics may foster
      further development of health promotion sciences, as it would allow for
      identification of success vectors in the domains of main characteristics of
      interventions/policies, their implementation, evaluation and monitoring
      processes.

PMID- 25604456
TI  - High prevalence and genetic diversity of noroviruses among children with sporadic
      acute gastroenteritis in Nanning City, China, 2010-2011.
AB  - A molecular epidemiological study of Norovirus (NoV) infections in children aged
      <5 years was conducted in the outpatient department of a hospital between January
      2010 and December 2011 in Nanning City, Guangxi Zhuang Autonomous Region of
      China. Fecal samples were collected from 354 pediatric patients with acute
      gastroenteritis, and were screened for the presence of NoV with one-step real
      time reverse-transcription polymerase chain reaction (RT-PCR). NoV genogroup II
      (GII) was detected in 28.5% (101/342) of samples, but no NoV GI was found. Eighty
      four of the NoV GII strains were successfully sequenced, and they were clustered
      into seven genotypes: GII.4 (77.4%), GII.2 (8.3%), GII.14 (4.8%), GII.7 (3.6%),
      GII.3 (2.4%), GII.6 (2.4%), and GII.12 (1.2%). The predominant GII.4 variant in
      circulation was variant 2006b (92.3%). Importantly, the emergence of variant
      GII.4 2010 was detected. NoV was detected throughout the year, but mainly during
      the cold months. The highest prevalence of NoV was detected in young children
      aged <2 years. The NoV detection rates did not differ significantly in males and
      females. This is the first report to demonstrate the high prevalence and genetic
      diversity of NoVs in children with sporadic acute gastroenteritis in Nanning. Our
      study findings indicate the need for continual surveillance to monitor
      epidemiological changes and potential new variants of these viruses.

PMID- 25604457
TI  - Prevalence of human papillomavirus and its genotype among 1336 invasive cervical
      cancer patients in Hunan province, central south China.
AB  - Existing data on the genotype distribution of human papillomavirus (HPV) are
      limited in Hunan province, central south China. To evaluate the prevalence of HPV
      infection and its genotype among women with invasive cervical cancer in Hunan, a
      total of 1,336 patients were included in this study between July 2012 and June
      2013. Eighteen high-risk and eight low-risk genotypes of HPV were detected by
      Luminex xMAP technology. The results show that HPV prevalence in invasive
      cervical cancer in Hunan was 75.7%. A single HPV infection was found in 82.3% of
      the HPV-positive samples, and 91.8% of the cases had high-risk HPV infection. The
      most common HPV type was HPV 16 (50.6%), followed by HPV 58 (12.4%), HPV 52
      (10.9%), HPV 18 (7.3%), HPV 33 (5.5%), HPV 59 (4.2%), HPV 39 (4.0%), HPV 61
      (3.4%), HPV 31 (3.3%), and HPV 56 (3.2%). A single infection with HPV 16 was
      detected in 42.5% of the samples, which was significantly more frequent than any
      other HPV type in this population. Dual-infection with HPV 16 and HPV 52 were
      relatively common. The available vaccines for HPV 16 and 18 are therefore
      expected to have a substantial impact on reducing the burden of cervical cancer
      in China, even though HPV 18 showed a lower frequency. In addition to HPV 16 and
      18, other HPV types including 58, 52, and 33, should be targeted in the next
      generation HPV vaccines.

PMID- 25604458
TI  - Molecular detection and characterization of BK and JC polyomaviruses in urine
      samples of renal transplant patients in Southern Brazil.
AB  - The human polyomaviruses JC (JCPyV) and BK (BKPyV) are widespread in the human
      population. Following the primary infection, virus reactivation may lead to
      nephropathy and graft rejection in renal transplant patients. This study was
      carried out to access the presence of BKPyV and JCPyV DNA in urine samples
      collected from renal transplant patients (n = 92) and healthy individuals (n =
      88) in Porto Alegre, Rio Grande do Sul. The samples were submitted to a nested
      PCR. A significantly higher frequency (P < 0.001) of BKPyV was found in renal
      transplant patients (65.2%) in comparison to the control group (32.9%). JCPyV was
      detected equally in both groups. Phylogenetic analysis of both BKPyV and JCPyV
      amplicons demonstrates the presence of the BKPyV subtypes I and II, whereas for
      JCPyV, four different groups are found (1, 2, 3, and 4).

PMID- 25604459
TI  - Identification of cytoplasmic proteins interacting with unliganded estrogen
      receptor alpha and beta in human breast cancer cells.
AB  - Estrogen receptor subtypes (ERalpha and ERbeta) are transcription factors sharing
      a similar structure but exerting opposite roles in breast cancer cells. Besides
      the well-characterized genomic actions of nuclear ERs upon ligand binding,
      specific actions of ligand-free ERs in the cytoplasm also affect cellular
      functions. The identification of cytoplasmic interaction partners of unliganded
      ERalpha and ERbeta may help characterize the molecular basis of the extra-nuclear
      mechanism of action of these receptors, revealing novel mechanisms to explain
      their role in breast cancer response or resistance to endocrine therapy. To this
      aim, cytoplasmic extracts from human breast cancer MCF-7 cells stably expressing
      tandem affinity purification-tagged ERalpha and ERbeta and maintained in estrogen
      free medium were subject to affinity-purification and MS analysis, leading to the
      identification of 84 and 142 proteins associated with unliganded ERalpha and
      ERbeta, respectively. Functional analyses of ER subtype-specific interactomes
      revealed significant differences in the molecular pathways targeted by each
      receptor in the cytoplasm. This work, reporting the first identification of the
      unliganded ERalpha and ERbeta cytoplasmic interactomes in breast cancer cells,
      provides novel experimental evidence on the nongenomic effects of ERs in the
      absence of hormonal stimulus. All MS data have been deposited in the
      ProteomeXchange with identifier PXD001202
      (http://proteomecentral.proteomexchange.org/dataset/PXD001202). 

PMID- 25604460
TI  - Postweaning isolation affects responses to incentive contrast in adulthood.
AB  - Adolescence is a time involving a series of changes in the use of appetitive
      reinforcers like food, as well as neuroendocrine changes like those taking place
      in the mesolimbic dopamine function. Social isolation from postnatal day 21 to 36
      in rats leads to behavioral and neurophysiological alterations such as increased
      consumption of appetitive reinforcers. The work is focused on studying how
      exposure to chronic stress induced by social isolation during adolescence can
      have a long-lasting effect on responses to reinforcement shifts in adulthood. Two
      experiments were performed in rats in order to analyze the effect of adolescent
      isolation on the responses to unanticipated shifts in reinforcement during
      adulthood, in reinforcement devaluation (32-4% of sucrose solution), increase (4
      32% of sucrose solution), and extinction (32-0% of sucrose solution) procedures.
      Adolescent isolation intensified the intake response resulting from a
      reinforcement increase (i.e., greater positive contrast), but had no effect on
      the response to reinforcement devaluation and omission. The implications of this
      procedure are discussed, along with the underlying behavioral and neurochemical
      mechanisms.

PMID- 25604461
TI  - Stacking interactions by two Phe side chains stabilize and orient assemblies of
      even the minimal amphiphilic beta-sheet motif.
AB  - Here we demonstrate that the smallest possible motif of the amphiphilic and
      pleated beta-strand structure can be generated using tri-peptides stabilized by
      pi-pi stacking interactions. Monitoring the early stages of Phe-Glu-Phe fibril
      formation revealed unique angular orientations. Phe-Glu-Phe fibrils were further
      exploited as adsorbing templates for metal ions. 

PMID- 25604462
TI  - Remembering the forgotten non-communicable diseases.
AB  - The forthcoming post-Millennium Development Goals era will bring about new
      challenges in global health. Low- and middle-income countries will have to
      contend with a dual burden of infectious and non-communicable diseases (NCDs).
      Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and
      diabetes, cause much health loss worldwide and are already widely recognised as
      doing so. However, 55% of the global NCD burden arises from other NCDs, which
      tend to be ignored in terms of premature mortality and quality of life reduction.
      Here, experts in some of these 'forgotten NCDs' review the clinical impact of
      these diseases along with the consequences of their ignoring their medical
      importance, and discuss ways in which they can be given higher global health
      priority in order to decrease the growing burden of disease and disability. 

PMID- 25604463
TI  - Anogenital giant seborrheic keratosis.
AB  - Seborrheic keratosis (SK) are very common benign epidermal tumors. Giant
      seborrheic keratosis (GSK) is a rare variant with clinical characteristics, which
      leads very often to misdiagnosis. A genital site of SK is very unusual clinical
      manifestation and although the cause is still unknown, current literature data
      point to a possible pathogenetic role of chronic friction and HPV infection. The
      rare genital localization makes Buschke-Lowenstein tumor and verrucous carcinoma
      important differential diagnoses. GSK may also show some clinical features of a
      melanoacanthoma, which makes cutaneous melanoma as another possible differential
      diagnosis. The clinical diagnosis of genital GSK is often a very difficult one,
      because the typical clinical features of GSK disappear and the most common
      dermoscopic features of GSK are usually not seen in the genital region lesions.
      The diagnosis of GSK of the anogenital area should be made only and always after
      the exact histological verification and variety of differential diagnosis should
      be carefully considered. The treatment of GSK is primary surgically. We present a
      rare case of GSK with concomitant HPV infection in the anogenital region of 72
      year-old patient. Surgical approach was performed with excellent outcome.

PMID- 25604466
TI  - Cucurbit[8]uril templated supramolecular ring structure formation and protein
      assembly modulation.
AB  - The interplay of Phe-Gly-Gly (FGG)-tagged proteins and bivalent FGG-tagged
      penta(ethylene glycol) as guest molecules with cucurbit[8]uril (Q8) hosts is
      studied to modulate the supramolecular assembly process. Ring structure formation
      of the bivalent guest molecule with Q8 leads to enhanced binding properties and
      efficient inhibition of protein assemblies. 

PMID- 25604465
TI  - Culicoides (Diptera: Ceratopogonidae) midges, the vectors of African horse
      sickness virus--a host/vector contact study in the Niayes area of Senegal.
AB  - BACKGROUND: African horse sickness (AHS) is an equine disease endemic to Senegal.
      The African horse sickness virus (AHSV) is transmitted to the mammalian hosts by
      midges of the Culicoides Latreille genus. During the last epizootic outbreak of
      AHS in Senegal in 2007, 1,169 horses died from this disease entailing an
      estimated cost of 1.4 million euros. In spite of the serious animal health and
      economic implications of AHS, very little is known about determinants involved in
      transmission such as contact between horses and the Culicoides species suspected
      of being its vectors. METHODS: The monthly variation in host/vector contact was
      determined in the Niayes area, Senegal, an area which was severely affected by
      the 2007 outbreak of AHS. A horse-baited trap and two suction light traps (OVI
      type) were set up at each of five sites for three consecutive nights every month
      for one year. RESULTS: Of 254,338 Culicoides midges collected 209,543 (82.4%)
      were female and 44,795 (17.6%) male. Nineteen of the 41 species collected were
      new distribution records for Senegal. This increased the number of described
      Culicoides species found in Senegal to 53. Only 19 species, of the 41 species
      found in light trap, were collected in the horse-baited trap (23,669 specimens)
      largely dominated by Culicoides oxystoma (22,300 specimens, i.e. 94.2%) followed
      by Culicoides imicola (482 specimens, i.e. 2.0%) and Culicoides kingi (446
      specimens, i.e. 1.9%). CONCLUSIONS: Culicoides oxystoma should be considered as a
      potential vector of AHSV in the Niayes area of Senegal due to its abundance on
      horses and its role in the transmission of other Culicoides-borne viruses.

PMID- 25604464
TI  - Plasticity of left perisylvian white-matter tracts is associated with individual
      differences in math learning.
AB  - Plasticity of white matter tracts is thought to be essential for cognitive
      development and academic skill acquisition in children. However, a dearth of high
      quality diffusion tensor imaging (DTI) data measuring longitudinal changes with
      learning, as well as methodological difficulties in multi-time point tract
      identification have limited our ability to investigate plasticity of specific
      white matter tracts. Here, we examine learning-related changes of white matter
      tracts innervating inferior parietal, prefrontal and temporal regions following
      an intense 2-month math tutoring program. DTI data were acquired from 18 third
      grade children, both before and after tutoring. A novel fiber tracking algorithm
      based on a White Matter Query Language (WMQL) was used to identify three sections
      of the superior longitudinal fasciculus (SLF) linking frontal and parietal (SLF
      FP), parietal and temporal (SLF-PT) and frontal and temporal (SLF-FT) cortices,
      from which we created child-specific probabilistic maps. The SLF-FP, SLF-FT, and
      SLF-PT tracts identified with the WMQL method were highly reliable across the two
      time points and showed close correspondence to tracts previously described in
      adults. Notably, individual differences in behavioral gains after 2 months of
      tutoring were specifically correlated with plasticity in the left SLF-FT tract.
      Our results extend previous findings of individual differences in white matter
      integrity, and provide important new insights into white matter plasticity
      related to math learning in childhood. More generally, our quantitative approach
      will be useful for future studies examining longitudinal changes in white matter
      integrity associated with cognitive skill development.

PMID- 25604467
TI  - Perceived health problems in swimmers according to the chemical treatment of
      water in swimming pools.
AB  - The objective of this study was to determine which chemical treatment used for
      disinfecting water in indoor swimming pools had the least impact on users'
      perceptions of health problems, and which generated the greatest satisfaction
      with the quality of the water. A survey on satisfaction and perceived health
      problems was given to 1001 users at 20 indoor swimming pools which used different
      water treatment methods [chlorine, bromine, ozone, ultraviolet lamps (UV) and
      salt electrolysis]. The findings suggest that there is a greater probability of
      perceived health problems, such as eye and skin irritation, respiratory problems
      and skin dryness, in swimming pools treated with chlorine than in swimming pools
      using other chemical treatment methods. Pools treated with bromine have similar,
      although slightly better, results. Other factors, such as age, gender, time of
      day of use (morning and afternoon) and type of user (competitive and
      recreational), can also affect the probability of suffering health problems. For
      all of the above, using combined treatment methods as ozone and UV, or salt
      electrolysis produces a lower probability of perceived health problems and
      greater satisfaction. 

PMID- 25604468
TI  - Effect of resveratrol on restoring spermatogenesis in experimental cryptorchid
      mice and analysis of related differentially expressed proteins.
AB  - The present study aimed to evaluate the effect of trans-Resveratrol on
      spermatogenesis. Male Kunming suckling mice (10 days old) were surgically
      rendered cryptorchid and subcutaneously injected with trans-Resveratrol at doses
      of 5, 10, 20, and 40 ug/g/day as groups I, II, III, and IV, respectively, for 35
      days. Animals in the control group received 10 uL/mouse/day of olive oil. Serum
      estradiol, testosterone, FSH, and LH levels were measured on day 45. Tissue
      analysis and sperm morphological abnormalities analysis were done. Results showed
      that in the control group and group I only spermatogonia and primary
      spermatocytes were present, whereas spermatogenesis was totally restored in
      groups II, III, and IV. Sperm counts in groups III and IV were remarkably higher
      than the control group (P<0.05). The morphological abnormalities in resveratrol
      treated groups were higher than the mature mice. Serum estradiol levels in the
      resveratrol-treated groups were not significantly different from the control
      group, but were lower than the mature mice (P<0.05). There was no significant
      difference in serum testosterone levels between the resveratrol-treated groups
      and mature mice, but the levels in the resveratrol-treated groups was
      significantly lower than the control group (P<0.05). No significant influence of
      trans-Resveratrol was observed on serum FSH levels in all cryptorchid mice. Serum
      LH levels in groups I, II, and III were higher than the control group. These
      results indicate that trans-Resveratrol restores spermatogenesis in cryptorchid
      mice. In addition, proteomic analysis between the 20 MUg/g/day resveratrol
      treated group and the control group was carried out, and five kinds of proteins
      (BAF250, ZFP261, CHD1L, RBBP9, and SOHLH2) were identified. The expression of
      SOHLH2 increased, while that of BAF250, ZFP261, CHD1L, and RBBP9 decreased in the
      20 ug/g/day resveratrol-treated group, indicating that SOHLH2 may contribute to
      testicular germ cell differentiation.

PMID- 25604469
TI  - Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity
      cardiac troponin in addition to N-terminal pro-brain natriuretic peptide.
AB  - OBJECTIVE: To measure plasma concentrations of high-sensitivity cardiac troponin
      T (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients
      with systemic sclerosis (SSc; scleroderma) and age- and sex-matched healthy
      control subjects, and to examine the contribution of traditional cardiovascular
      risk factors and SSc features to the concentrations of these 2 cardiac
      biomarkers. METHODS: Plasma HS-cTnT and NT-proBNP concentrations were measured
      using the electrochemiluminescence method and sandwich immunoassay, respectively.
      RESULTS: The study group comprised 161 unrelated patients with SSc and 213
      matched control subjects. HS-cTnT and NT-proBNP plasma levels were significantly
      increased in SSc patients compared with controls (both P < 0.001). Similar
      results were observed in the subgroup of patients with SSc who had no
      cardiovascular risk factors (n = 72). Multivariate logistic regression analysis
      confirmed diabetes mellitus (P = 0.006), high blood pressure (P = 0.021),
      precapillary pulmonary hypertension (P = 0.039), and the diffuse cutaneous SSc (P
      = 0.004) as factors independently associated with an HS-cTnT level of >14
      ng/liter. Increased NT-proBNP concentrations were associated only with the
      presence of precapillary pulmonary hypertension (P < 0.001). Normal
      concentrations of both HS-cTnT and NT-proBNP had a high negative predictive value
      for precapillary pulmonary hypertension (92%), and the combination of increased
      values of these 2 markers had the highest strength of association with
      precapillary pulmonary hypertension in logistic regression analysis. CONCLUSION:
      HS-cTnT and NT-proBNP concentrations are increased in patients with SSc, even in
      those who are free of cardiovascular risk factors. These easily obtained
      biomarkers may be useful for systematic evaluation and stratification of SSc
      patients, especially to identify those at risk of pulmonary hypertension.

PMID- 25604470
TI  - Effect of testing experience and profession on provider acceptability of rapid
      HIV testing after implementation in public sexual health clinics in Sydney.
AB  - OBJECTIVES: Rapid HIV testing (RHT) is well established in many countries, but it
      is new in Australia since a policy change in 2011. We assessed service provider
      acceptability of RHT before and after its implementation in four Sydney public
      sexual health clinics. METHODS: Service providers were surveyed immediately after
      training in RHT and again 6-12 months later. Differences in mean scores between
      survey rounds were assessed via t-tests, with stratification by profession and
      the number of tests performed. RESULTS: RHT was rated as highly acceptable among
      staff at baseline and acceptability scores improved between survey rounds. Belief
      in being sufficiently skilled and experienced to perform RHT (P = 0.004) and
      confidence in the delivery of nonreactive results increased (P = 0.007), while
      the belief that RHT was disruptive declined (P = 0.001). Acceptability was higher
      for staff who had performed a greater number of tests regarding comfort with
      their role in RHT (P = 0.004) and belief that patients were satisfied with RHT (P
      = 0.007). Compared with nurses, doctors had a stronger preference for a faster
      rapid test (P = 0.027) and were more likely to agree that RHT interfered with
      consultations (P = 0.014). CONCLUSIONS: Differences in responses between
      professions may reflect differences in staff roles, the type of patients seen by
      staff and the model of testing used, all of which may affect the number of tests
      performed by staff. These findings may inform planning for how best to implement
      RHT in clinical services.

PMID- 25604471
TI  - Recommendations for standardization of laboratory testing for drug-induced immune
      thrombocytopenia: communication from the SSC of the ISTH.

PMID- 25604472
TI  - 'Imagine if I gave up smoking ...': a qualitative exploration of Aboriginal
      participants' perspectives of a self-management pilot training intervention.
AB  - This paper reports on a pilot qualitative study investigating Aboriginal
      participants' perspectives of the Flinders Living Well Smoke Free (LWSF)
      'training intervention'. Health workers nationally have been trained in this
      program, which offers a self-management approach to reducing smoking among
      Aboriginal clients. A component of the training involves Aboriginal clients
      volunteering their time in a mock care-planning session providing the health
      workers with an opportunity to practise their newly acquired skills. During this
      simulation, the volunteer clients receive one condensed session of the LWSF
      intervention imitating how the training will be implemented when the health
      workers have completed the training. For the purpose of this study, 10 Aboriginal
      clients who had been volunteers in the mock care-planning process, underwent a
      semi-structured interview at seven sites in Australia, including mainstream
      health services, Aboriginal community controlled health services and remote
      Aboriginal communities. The study aimed to gauge their perspectives of the
      training intervention they experienced. Early indications suggest that Aboriginal
      volunteer clients responded positively to the process, with many reporting
      substantial health behaviour change or plans to make changes since taking part in
      this mock care-planning exercise. Enablers of the intervention are discussed
      along with factors to be considered in the training program.

PMID- 25604473
TI  - Measuring naturally acquired ex vivo IFN-gamma responses to Plasmodium falciparum
      cell-traversal protein for ookinetes and sporozoites (CelTOS) in Ghanaian adults.
AB  - BACKGROUND: A malaria vaccine that targets the sporozoite/liver stage parasites
      could potentially prevent blood stage infection and the associated clinical
      symptoms. Identification of sporozoite/liver stage antigens is, therefore,
      crucial for the development of effective vaccines. Cell-traversal protein for
      ookinetes and sporozoites (CelTOS) is a highly conserved antigen involved in
      sporozoite motility and hepatocyte invasion and has been shown to induce
      significant IFN-gamma production in PBMCs from radiation-attenuated sporozoite
      immunized malaria-naive individuals. The aim of this study was to ascertain
      whether such CelTOS-specific recall responses are also induced in individuals
      with natural exposure to Plasmodium falciparum. METHODS: Ex vivo IFN-gamma
      responses to 15mer overlapping peptide pools covering the entire sequence of
      CelTOS and five other candidate antigens, CSP, AMA1, MSP1, TRAP and LSA1, were
      characterized using PBMCs from 35 malaria exposed adults. Responses to four
      CelTOS peptide pools (CelTp1, CelTp2, CelTp3 and CelTp4), a pool containing
      peptides from the entire CelTOS antigen (CelTTp), and pools comprised of
      overlapping peptides from each of the other five malaria antigens were assessed
      by ex vivo ELISpot assay. A positive IFN-gamma response for stimulants was
      defined by two criteria; a stimulation index of two or greater relative to the
      unstimulated control, and a difference of 10 or greater in spot forming cells
      between stimulant and the unstimulated control. RESULTS: Of the 35 volunteers
      tested, five had positive IFN-gamma recall responses against the four different
      CelTOS pools while four volunteers made responses against the CelTTp pool; six
      volunteers were, therefore, positive with CelTOS. By contrast, six volunteers
      responded to AMA1, seven to LSA1, 15 to MSP1 and two volunteers responded against
      CSP and TRAP. CONCLUSIONS: These results suggest natural malaria transmission
      induces CelTOS-specific ex vivo IFN-gamma in Ghanaian adults and that the
      frequency of these responses was similar to those of other previously
      characterized malaria antigens. These findings support the further evaluation of
      CelTOS as a pre-erythrocytic candidate antigen for inclusion in a potential multi
      antigen vaccine.

PMID- 25604474
TI  - The biological activity of Zeise's salt and its derivatives.
AB  - With the aim to design new biologically active bioinorganic drugs of aspirin,
      whose mode of action is based on the inhibition of the cyclooxygenase(COX)
      enzymes, derivatives of Zeise's salt were synthesized in this structure-activity
      relationship study. Surprisingly, not only these Zeise-aspirin compounds but also
      Zeise's salt itself showed high inhibitory potency against COX enzymes in in
      vitro assays. In contrast, potassium tetrachloroplatinate and cisplatin did not
      influence the enzyme activity at equimolar concentrations. It was demonstrated by
      LC-ESI tandem-mass spectrometry that Zeise's salt platinates the essential amino
      acids Tyr385 (active site of the enzyme) and Ser516 (will be acetylated by
      aspirin) of COX-1, thereby strongly impairing the function of the enzyme. This
      finding demonstrates for the first time that Zeise's salt is pharmacologically
      active and is a potent enzyme inhibitor. 

PMID- 25604475
TI  - The relationship between driving simulation performance and obstructive sleep
      apnoea risk, daytime sleepiness, obesity and road traffic accident history of
      commercial drivers in Turkey.
AB  - BACKGROUND: Driving performance is known to be very sensitive to cognitive
      psychomotor impairment. The aim of the study was to determine the relationship
      between obesity, risk of obstructive sleep apnoea (OSA), daytime sleepiness,
      history of road traffic accident (RTA) and performance on a driving simulator,
      among commercial drivers. METHODS: We examined commercial vehicle drivers
      admitted to Psycho-Technical Assessment System (PTAS), which is a computer-aided
      system that includes a driving simulator test and tests assessing psychomotor
      cognitive skills required for driving. Risk of OSA and daytime sleepiness were
      assessed by the Berlin Questionnaire and the Epworth Sleepiness Scale (ESS),
      respectively. RESULTS: A total of 282 commercial vehicle drivers were
      consecutively enrolled. The age range was 29-76 years. Thirty drivers were at
      high risk of OSA. Median ESS of the group was 2 (0-20). Forty-seven percent of
      the subjects at high risk of OSA failed in early reaction time test, while 28% of
      the drivers with low risk of OSA failed (p = 0.03). The obese drivers failed the
      peripheral vision test when compared with non-obese drivers (p = 0.02). ESS was
      higher for drivers with a history of RTA when compared to those without RTA (p =
      0.02). CONCLUSIONS: Cognitive-psychomotor functions can be impaired in obese and
      high risk of OSA patients. In our opinion, requiring obese and/or high risk of
      OSA drivers to take PTAS tests that assess driving skills and psychomotor
      cognitive functions crucial to those skills would significantly improve road
      traffic safety, which is of considerable importance to public health.

PMID- 25604476
TI  - Co-upregulation of Toll-like receptors 2 and 6 on peripheral blood cells in
      patients with obstructive sleep apnea.
AB  - PURPOSE: Toll-like receptor (TLR) 2 can heterodimerise with TLR6 to detect
      diacylated lipoproteins. Hypoxia inducible factor-1 alpha co-ordinates selective
      induction of TLR2 and TLR6 during persistent hypoxia. We hypothesized that TLR
      2/6 co-expression may be upregulated by chronic intermittent hypoxia with re
      oxygenation (IHR) in obstructive sleep apnea (OSA). METHODS: TLR2/6 expressions
      on blood immune cells were measured in 144 patients with sleep-disordered
      breathing (SDB), including primary snoring (PS, n = 24), moderate to severe OSA
      (MSO, n = 60), very severe OSA (VSO, n = 36), and very severe OSA on continuous
      positive airway pressure (CPAP) treatment (VSOC, n = 24). An in vitro IHR
      experiment was also undertaken. RESULTS: Patients in both the MSO and VSO groups
      had increased TLR2/6 co-expression on CD16(+) neutrophil than those in the PS
      group. Patients in the VSOC group had reduced TLR2/6 co-expression on neutrophil
      than those in either the MSO or VSO group. Blood absolute neutrophil count was
      positively but weakly correlated with TLR2/6 co-expression on neutrophil. TLR2/6
      co-expressions on both CD14(+) monocyte and CD3(+)CD4(+)T helper cell, and TLR2
      expressions on both monocyte and T helper cell in SDB patients with low Minimum
      SaO2 (?70%) were all higher than those with high Minimum SaO2. In vitro IHR for 1
      4 days resulted in TLR2/6 co-upregulation on both neutrophil and monocyte.
      CONCLUSIONS: OSA patients had increased TLR2/6 co-expressions on blood immune
      cells, which were related to their immune cell counts and could be reversed with
      CPAP treatment. In vitro IHR could induce TLR2/6 co-upregulation.

PMID- 25604477
TI  - Effect of different oxygen desaturation threshold levels on hypopnea scoring and
      classification of severity of sleep apnea.
AB  - PURPOSE: Recently, there has been a debate about the rules used to score hypopnea
      events. The purpose of this study was to examine the effect of different oxygen
      desaturation threshold (ODT) levels on the apnea-hypopnea index (AHI) and on a
      recently introduced parameter, adjusted AHI. Adjusted AHI incorporates the
      severity of individual breathing cessation events. We also aimed to clarify the
      impact of the different ODT levels on the current classification of obstructive
      sleep apnea (OSA) severity. METHODS: Ambulatory polygraphic recordings of 68
      patients (19 F/49 M, median age 53.2 years, AHI >=5) were analyzed
      retrospectively. Hypopneas were defined as >=30% drop in airflow for >=10 s
      associated with >=2% oxygen desaturation (ODT2%), and after that, using stricter
      ODT criteria (ODT3%-ODT8%). RESULTS: Compared to ODT4%, the ODT3% resulted in 5.6
      events/h higher median conventional AHI, but only 1.5 events/h higher median
      adjusted AHI. A significant rearrangement of patients between the clinical
      severity categories took place when using different ODTs. When assessing with
      ODT3% instead of ODT4%, the portion of the patients with moderate or severe OSA
      (AHI >=15) raised from 29.4 to 73.5% using conventional AHI, but only marginally,
      i.e., from 73.5 to 77.9%, using the adjusted AHI. CONCLUSIONS: The conventional
      AHI was found to be susceptible even to minor changes in ODT level which may lead
      to substantial variability in AHI-based classification of disease severity. Since
      the adjusted AHI comprises information on severity of individual breathing
      cessations, it reduces the variability related to ODT levels used in hypopnea
      scoring and can increase the accuracy of estimation of OSA severity.

PMID- 25604478
TI  - A field investigation into a suspected outbreak of pyrrolizidine alkaloid
      toxicosis in horses in western Queensland.
AB  - A disease outbreak investigation was conducted in western Queensland to
      investigate a rare suspected outbreak of pyrrolizidine alkaloid (PA) toxicosis in
      horses. Thirty five of 132 horses depastured on five properties on the Mitchell
      grass plains of western Queensland died in the first six months of 2010. Clinical
      pathological findings were consistent with PA toxicosis. A local variety of
      Crotalaria medicaginea was the only hepatotoxic plant found growing on affected
      properties. Pathology reports and departure and arrival dates of two brood mares
      provided evidence of a pre wet season exposure period. All five affected
      properties experienced a very dry spring and early summer preceded by a large
      summer wet season. The outbreak was characterised as a point epidemic with a
      sudden peak of deaths in March followed by mortalities steadily declining until
      the end of June. The estimated morbidity (serum IGG>50IU/L) rate was 76%. Average
      crude mortality was 27% but higher in young horses (67%) and brood mares (44%).
      Logistic regression analysis showed that young horses and brood mares and those
      grazing denuded pastures in December were most strongly associated with dying
      whereas those fed hay and/or grain based supplements were less likely to die.
      This is the first detailed study of an outbreak of PA toxicosis in central
      western Queensland and the first to provide evidence that environmental
      determinants were associated with mortality, that the critical exposure period
      was towards the end of the dry season, that supplementary feeding is protective
      and that denuded pastures and the horses physiological protein requirement are
      risk factors. 

PMID- 25604479
TI  - Complete mitochondrial genome of the big-eared horseshoe bat Rhinolophus macrotis
      (Chiroptera, Rhinolophidae).
AB  - We sequenced and characterized the complete mitochondrial genome of the big-eared
      horseshoe bat, Rhinolophus macrotis. Total length of the mitogenome is 16,848 bp,
      with a base composition of 31.2% A, 25.3% T, 28.8% C and 14.7% G. The mitogenome
      consists of 13 protein-coding genes, 2 rRNA (12S and 16S rRNA) genes, 22 tRNA
      genes and 1 control region. It has the same gene arrangement pattern as those of
      typical vertebrate mitochondrial genome. The results will contribute to our
      understanding of the taxonomic status and evolution in the genus Rhinolophus
      bats.

PMID- 25604480
TI  - The completed eight chloroplast genomes of tomato from Solanum genus.
AB  - In this study, we fully assembled eight tomato chloroplast (cp) genomes using
      next-generation sequencing data. It will provide valuable information for
      phylogenetic and cp genetic engineering studies of Solanum genus. The total
      genome size varied from 155,443 to 155,561 bp in length, containing a pair of
      inverted repeats (IRs) of 25,612-25,639 bp, which were separated by large single
      copy (LSC) and small single copy (SSC) of 85,857-85,911 bp and 18,362-18,387 bp
      in size, respectively. The overall GC contents of the chloroplast genome were
      37.84-37.88%. The same set of 112 unique genes was annotated from eight cp
      genomes, including 78 protein coding genes, 30 tRNA genes, and four rRNA genes.
      Among these, 17 are duplicated in the inverted repeat regions, 15 genes contained
      one intron, and three genes (rps12, clpP, and ycf3) comprising two introns.

PMID- 25604481
TI  - Cholera in travelers: shifting tides in epidemiology, management, and prevention.
AB  - The distribution of cholera's devastating effects has changed. While cholera is
      endemic in 50 countries mostly in Asia and Africa, more than half of the cases
      reported in 2012 were in the Western Hemisphere, predominantly Haiti. Since the
      current epidemic began in Haiti in 2010, there has been spread to the Dominican
      Republic, Cuba, and most recently Mexico. Several recent case reports document
      individuals returning home from affected areas with diarrhea from cholera, in
      some cases severe. Hopeful news reported the containment of an outbreak through
      the use of a Vibrio cholera vaccine. There are safe and effective oral cholera
      vaccines available and recommended in outbreaks and endemic areas, although they
      are not currently available in the USA or to travelers. This review aims to
      discuss the latest data to aid our current recommendations for the prevention of
      cholera in travelers beyond standard personal and food hygiene precautions for
      the prevention of travelers' diarrhea and to offer insights on the most current
      data available about cholera vaccine progress and potential use. 

PMID- 25604484
TI  - Primary prosthetic voice rehabilitation in patients after laryngectomy:
      applications and pitfalls.
AB  - The use of the tracheoesophageal (T-E) silicone rubber voice prosthesis is the
      most effective and well-established procedure to restore the voice in patients
      after laryngectomy. The prosthesis is usually well-tolerated with only minor
      complications. Severe complications are rare. In this article we present our
      experience with the prosthetic technique at the Clinic of Otorhinolaryngology and
      Head and Neck Surgery in University Hospital in Martin, Slovakia between the
      years 2005-2013 and report a case of a 48-year-old man with secondary prosthesis
      inserted through a T-E shunt 16 months after laryngectomy. On the 6th day after
      the insertion, the shunt decayed. After prosthesis removal the tissue defect was
      sutured. Due to repetitive tissue decay, reconstruction of the trachea and
      esophagus became necessary. On the 10th day, peritracheoesophageal fistula
      developed and gastrostomy was performed. Because of intense fibrotic and
      inflammatory changes, further reconstruction was not indicated. After 6 months,
      esophageal stenosis occurred and endoscopic dilation under local anaesthesia was
      performed. The T-E voice prosthesis has become one of the choices for voice
      rehabilitation following total laryngectomy and may improve the patient's long
      term quality of life. The overall risk of severe complications seems relatively
      low. Nonetheless, some complications might be challenging and might require
      specific management. 

PMID- 25604483
TI  - Identification of non-Ser/Thr-Pro consensus motifs for Cdk1 and their roles in
      mitotic regulation of C2H2 zinc finger proteins and Ect2.
AB  - The cyclin B-dependent protein kinase Cdk1 is a master regulator of mitosis and
      phosphorylates numerous proteins on the minimal consensus motif Ser/Thr-Pro (S/T
      P). At least in several proteins, however, not well-defined motifs lacking a Pro
      in the +1 position, referred herein to as non-S/T-P motifs, have been shown to be
      phosphorylated by Cdk1. Here we show that non-S/T-P motifs in fact form consensus
      sequences for Cdk1 and probably play roles in mitotic regulation of
      physiologically important proteins. First, we show, by in vitro kinase assays,
      that previously identified non-S/T-P motifs all harbour one or more C-terminal
      Arg/Lys residues essential for their phosphorylation by Cdk1. Second, using
      Arg/Lys-scanning oriented peptide libraries, we demonstrate that Cdk1
      phosphorylates a minimal sequence S/T-X-X-R/K and more favorable sequences (P)-X
      S/T-X-[R/K](2-5) as its non-S/T-P consensus motifs. Third, on the basis of these
      results, we find that highly conserved linkers (typically, T-G-E-K-P) of C2H2
      zinc finger proteins and a nuclear localization signal-containing sequence
      (matching P-X-S-X-[R/K]5) of the cytokinesis regulator Ect2 are inhibitorily
      phosphorylated by Cdk1, well accounting for the known mitotic regulation and
      function of the respective proteins. We suggest that non-S/T-P Cdk1 consensus
      motifs identified here may function to regulate many other proteins during
      mitosis.

PMID- 25604482
TI  - Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the
      acute phase of ischemic stroke.
AB  - Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term
      potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D
      aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects
      synaptic plasticity in an NMDAR dependent manner. Since its activity and
      concentration is increased in brain tissue upon acute stroke, we sought to
      clarify whether thrombin could mediate iLTP through the activation of its
      receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were
      obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia
      was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific
      ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal
      slices, while OGD-induced changes in prothrombin mRNA levels were assessed by
      (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust
      potentiation of excitatory synaptic strength was detected, which occluded the
      ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1
      blocked iLTP and restored the physiological, stimulus induced LTP. Our study
      provides important insights on the early changes occurring at excitatory synapses
      after ischemia and indicates the thrombin/PAR1 pathway as a novel target for
      developing therapeutic strategies to restore synaptic function in the acute phase
      of ischemic stroke. 

PMID- 25604485
TI  - Effect of local wound infiltration and transversus abdominis plane block on
      morphine use after laparoscopic colectomy: a nonrandomized, single-blind
      prospective study.
AB  - BACKGROUND: Recently, nonopioid-based treatment modalities have been used to
      improve analgesia and decrease opioid-related side effects after surgery.
      Transversus abdominis plane (TAP) block and local infiltration of the surgical
      wound are commonly used multimodal analgesia techniques after abdominal surgery;
      however, few studies have compared the effectiveness of a TAP block with that of
      local infiltration of surgical wounds in patients who have undergone laparoscopic
      colorectal surgery. MATERIALS AND METHODS: Sixty patients undergoing laparoscopic
      colorectal surgery participated in this prospective comparative study. All
      patients were allocated to 1 of 2 groups as follows: the TAP group or the
      infiltration group. Patients in the TAP group received bilateral TAP blocks at
      the end of the surgery. Patients in the infiltration group received local
      infiltration of anesthetics in the surgical wounds after closure of the
      peritoneum. All patients received postoperative analgesia with morphine as a
      patient-controlled analgesia. Opioid consumption and pain scores were recorded at
      2, 6, 24, and 48 h after the operation. RESULTS: The characteristics of patients
      in the TAP group (n = 30) and local infiltration group (n = 29) were comparable.
      Pain scores while coughing and at rest were not different between the two groups.
      Postoperative morphine use was significantly reduced in the TAP group compared
      with that in the local infiltration group at 2-6 h (2.9 +/- 1.9 mg versus 4.5 +/-
      3.2 mg, P = 0.02), 6-24 h (5.5 +/- 3.3 mg versus 10.2 +/- 8.4 mg, P = 0.00), the
      first 24 h (16.6 +/- 6.6 mg versus 24.0 +/- 9.7 mg), and 48 h (23.6 +/- 8.2 mg
      versus 31.8 +/- 12.5 mg, P = 0.00). No differences in rescue analgesic use or
      side effects were noted between the groups. CONCLUSIONS: Compared with local
      anesthetic infiltration, bilateral TAP blocks decreased the cumulative morphine
      use at 24 h and 48 h postoperatively in patients who had undergone laparoscopic
      colorectal surgery.

PMID- 25604486
TI  - New rarebit vision test captures macular deficits hidden to acuity tests.
AB  - PURPOSE: Evaluation of a new personal-computer-based vision test aimed for rapid
      and accurate assessment of macular conditions such as age-related macular
      degeneration (AMD). METHODS: The new test depends on segmented digits defined by
      rarebits, that is, receptive field-size bright dots briefly presented against a
      dark background. Digit size was fixed at 40 * 50 min of arc. Digit positions were
      varied at random within a 4.6 * 3.5-degree test field. There were no fixation
      demands. The number of rarebits per digit segment could be varied between 3 (the
      minimum needed for veridical perception) and 128, in 11 preset steps. The test
      task was to find the smallest rarebit number required to recognize the test
      digits. Thirty-seven patients with various stages of AMD and 25 control subjects
      participated in the evaluation, which also included a standard acuity test.
      RESULTS: Analysis of receiver operating characteristics indicated significantly
      better discrimination by the rarebit test. Rarebit numbers >16 appeared to
      reliably indicate the presence of oedema. CONCLUSION: The rarebit test appeared
      well suited for fine grading of vision in AMD. The simple set-up and the lack of
      fixation demands made for practicable examinations of short durations. The test
      is available for free on the Internet.

PMID- 25604487
TI  - Diazole-based powdered cocrystal featuring a helical hydrogen-bonded network:
      structure determination from PXRD, solid-state NMR and computer modeling.
AB  - We present the structure of a new equimolar 1:1 cocrystal formed by 3,5-dimethyl
      1H-pyrazole (dmpz) and 4,5-dimethyl-1H-imidazole (dmim), determined by means of
      powder X-ray diffraction data combined with solid-state NMR that provided insight
      into topological details of hydrogen bonding connectivities and weak interactions
      such as CH...pi contacts. The use of various 1D/2D (13)C, (15)N and (1)H high
      resolution solid-state NMR techniques provided structural insight on local length
      scales revealing internuclear proximities and relative orientations between the
      dmim and dmpz molecular building blocks of the studied cocrystal. Molecular
      modeling and DFT calculations were also employed to generate meaningful
      structures. DFT refinement was able to decrease the figure of merit R(F(2)) from
      ~11% (PXRD only) to 5.4%. An attempt was made to rationalize the role of NH...N
      and CH...pi contacts in stabilizing the reported cocrystal. For this purpose four
      imidazole derivatives with distinct placement of methyl substituents were reacted
      with dmpz to understand the effect of methylation in blocking or enabling certain
      intermolecular contacts. Only one imidazole derivative (dmim) was able to
      incorporate into the dmpz trimeric motif thus resulting in a cocrystal, which
      contains both hydrophobic (methyl groups) and hydrophilic components that self
      assemble to form an atypical 1D network of helicoidal hydrogen bonded pattern,
      featuring structural similarities with alpha-helix arrangements in proteins. The
      1:1 dmpz...dmim compound I is the first example of a cocrystal formed by two
      different azoles. 

PMID- 25604488
TI  - Safety and efficacy of splenic artery embolization for portal hyperperfusion in
      liver transplant recipients: a 5-year experience.
AB  - Severe portal hyperperfusion (PHP) after liver transplantation has been shown to
      cause intrahepatic arterial vasoconstriction secondary to increased adenosine
      washout (hepatic artery buffer response). Clinically, posttransplant PHP can
      cause severe cases of refractory ascites and hydrothorax. In the past, we
      reported our preliminary experience with the use of splenic artery embolization
      (SAE) as a way to reduce PHP. Here we present our 5-year experience with SAE in
      orthotopic liver transplantation (OLT). Between January 2007 and December 2011,
      681 patients underwent OLT at our institution, and 54 of these patients underwent
      SAE for increased hepatic arterial resistance and PHP (n=42) or refractory
      ascites/hepatic hydrothorax (n=12). Patients undergoing SAE were compared to a
      control group matched by year of embolization, calculated Model for End-Stage
      Liver Disease score, and liver weight. SAE resulted in improvements in hepatic
      artery resistive indices (0.92+/-0.14 and 0.76+/-0.10 before and after SAE,
      respectively; P<0.001) and improved hepatic arterial blood flow (HAF; 15.6+/-9.69
      and 28.7+/-14.83, respectively; P<0.001). Calculated splenic volumes and
      spleen/liver volume ratios were correlated with patients requiring SAE versus
      matched controls (P=0.002 and P=0.001, respectively). Among the 54 patients
      undergoing SAE, there was 1 case of postsplenectomy syndrome. No abscesses,
      significant infections, or bleeding was noted. We thus conclude that SAE is a
      safe and effective technique able to improve HAF parameters in patients with
      elevated portal venous flow and its sequelae.

PMID- 25604490
TI  - Giardia duodenalis and soil-transmitted helminths infections in children in Sao
      Tome and Principe: do we think Giardia when addressing parasite control?
AB  - Giardia duodenalis prevalence is commonly as high as soil-transmitted helminths
      (STH), nevertheless is not considered for large-scale chemotherapy through mass
      drug administration (MDA) due to its short incubation period and frequent
      reinfections, its control being associated to improving access to water and
      sanitation. A study enrolling 444 children attending preschools was conducted in
      May 2011 during a deworming campaign. Faecal samples were obtained and analysed
      through microscopy of wet mounting and after Kato-Katz and formol-ether
      concentration techniques. The majority of children were infected with at least
      one pathogenic parasite (86.7%, 385 of 444). Ascaris lumbricoides and Trichuris
      trichiura (56.3%, 250 of 444 and 52.5%, 233 of 444, respectively) were the most
      frequent parasites followed by G. duodenalis infecting 41.7% (185 of 444) of the
      children. The present work aimed at obtaining updated information concerning
      intestinal parasite infections in children attending preschools in Sao Tome and
      Principe and to contribute for the adequate management of the enteric infections.

PMID- 25604489
TI  - Challenges in the diagnosis and management of neonatal sepsis.
AB  - Neonatal sepsis is the third leading cause of neonatal mortality and a major
      public health problem, especially in developing countries. Although recent
      medical advances have improved neonatal care, many challenges remain in the
      diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis
      is complicated by the frequent presence of noninfectious conditions that resemble
      sepsis, especially in preterm infants, and by the absence of optimal diagnostic
      tests. Since neonatal sepsis is a high-risk disease, especially in preterm
      infants, clinicians are compelled to empirically administer antibiotics to
      infants with risk factors and/or signs of suspected sepsis. Unfortunately, both
      broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are
      associated with adverse outcomes and increase antimicrobial resistance rates.
      Given the high incidence and mortality of sepsis in preterm infants and its long
      term consequences on growth and development, efforts to reduce the rates of
      infection in this vulnerable population are one of the most important
      interventions in neonatal care. In this review, we discuss the most common
      questions and challenges in the diagnosis and management of neonatal sepsis, with
      a focus on developing countries. 

PMID- 25604492
TI  - Fibroblasts of recipient origin contribute to airway fibrosis in murine tracheal
      transplantations.

PMID- 25604491
TI  - alpha-Thalassaemia trait is associated with antibody prevalence against malaria
      antigens AMA-1 and MSP-1.
AB  - A longitudinal study was conducted in a low endemic area in northern Tanzania to
      examine the influence of the alpha-thalassaemia trait on malaria incidence and
      antibody responses to malaria apical membrane antigen-1 (AMA-1) and merozoite
      surface protein1-19 (MSP-119). Out of 394 children genotyped for alpha
      thalassaemia trait, 4.1% (16 of 394) and 30.7% (121 of 394) were homozygous and
      heterozygous, respectively. During the 1 year follow-up, four incidents of
      malaria cases were detected without an evident association with alpha
      thalassaemia. Being heterozygous or homozygous for alpha-thalassaemia was
      associated with an increased prevalence of antibodies to AMA-1 [odds ratio (OR):
      1.83, 95% confidence interval (CI): 1.07-3.12, p = 0.027] and MSP-1 (OR: 2.04,
      95% CI: 1.16-3.60, p = 0.013) after adjustment for age and reported bednet use.
      The observed association between alpha-thalassaemia and malaria antibody
      responses may reflect longer-term differences in antigen exposure or differences
      in antibody acquisition upon exposure in this low endemic setting.

PMID- 25604493
TI  - Viruses, apoptosis, and neuroinflammation--a double-edged sword.
AB  - Apoptosis, or programmed cell death, is a fundamental and widespread cell
      biological process that is distinct from cell necrosis and can be induced by a
      wide variety of stimuli including viral infections. Apoptosis may occur via
      either the intrinsic or extrinsic pathways and confers several advantages to the
      virally infected host including the prevention of further viral propagation and
      the potential inhibition and resolution of inflammatory processes. Several
      viruses have been shown to have the capacity to induce apoptosis in susceptible
      cells including herpes simplex virus, Varicella-zoster virus, rabies virus, human
      immunodeficiency virus, and reovirus. Apoptosis has also been observed in human
      African trypanosomiasis which is an infection caused by a protozoan parasite. The
      mechanisms leading to apoptosis may differ depending on the type of infection.
      Apoptosis has been reported in several neurodegenerative diseases and also
      psychiatric disorders but the true clinical significance of such observations is
      not certain, and, though interesting, it is very difficult to ascribe causation
      in these conditions. The presence of inflammation in the central nervous system
      in any neurological condition, including those associated with a viral infection,
      is not necessarily an absolute marker of serious disease and the notion of 'good'
      versus 'bad' inflammation is considered to be valid in some circumstances. The
      precise relationship between viruses, apoptosis, and inflammation is viewed as a
      complex one requiring further investigation to unravel and understand its nature.

PMID- 25604494
TI  - Association between brain volumes and HAND in cART-naive HIV+ individuals from
      Thailand.
AB  - This study aimed to determine the effects of human immunodeficiency virus (HIV)
      on brain structure in HIV-infected individuals with and without HIV-associated
      neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+,
      treatment-naive, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive
      impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated
      dementia HAD), and 37 HIV+, treatment-naive, individuals with normal cognitive
      function (HIV+HAND-) underwent magnetic resonance imaging (MRI) and
      neuropsychological assessment. The HIV-infected participants had a mean (SD) age
      of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83-324), and
      mean (IQR) log10 plasma viral load of 4.81 (4.39-5.48). Six regions of interest
      were selected for analyses including total and subcortical gray matter, total
      white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group
      exhibited significantly smaller brain volumes compared to the HIV-uninfected
      group in subcortical gray and total gray matter; however, there were no
      statistically significant differences in brain volumes between the HIV+HAND+ and
      HIV+HAND- groups or between HIV+/HAND- and controls. CD4 count at time of
      combination antiretroviral therapy (cART) initiation was associated with total
      and subcortical gray matter volumes but not with cognitive measures. Plasma viral
      load correlated with neuropsychological performance but not brain volumes. The
      lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND-
      suggests that brain atrophy is not a sensitive measure of HAND in subjects
      without advanced immunosuppression. Alternatively, current HAND diagnostic
      criteria may not sufficiently distinguish patients based on MRI measures of brain
      volumes.

PMID- 25604496
TI  - Clinical associations of white matter damage in cART-treated HIV-positive
      children in South Africa.
AB  - A range of factors contributes to white matter damage in vertically infected HIV
      positive children. These may include combination antiretroviral treatment (cART)
      regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant
      clinical variables, and cognitive functioning. We explored associations between a
      number of these factors and diffusion tensor imaging (DTI) measures in 50 cART
      treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion
      (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48
      cerebral white matter regions. Significant associations between a number of the
      clinical variables and white matter integrity were found. Decreased FA, a measure
      of neuronal damage, was associated with being on second-line cART, low
      hemoglobin, and younger age. Children with increased MD, a measure of neuronal
      damage, were younger, had reduced albumin and hemoglobin, and increased viral
      load. Decreased AD, a measure of axonal damage, was associated with increased
      viral load and total protein, decreased albumin and hemoglobin, younger age,
      poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a
      measure of myelin loss, was associated with younger age, low current CD4 count,
      low albumin and hemoglobin, and higher viral load and total protein. The current
      findings underline the possible association of first-line treatment failure with
      white matter brain dysfunction in pediatric neuroHIV and the importance of
      examining the effects of HIV disease in the context of treatable clinical
      variables such as anemia and nutritional status.

PMID- 25604495
TI  - Soluble insulin receptor as a source of insulin resistance and cognitive
      impairment in HIV-seropositive women.
AB  - Insulin resistance occurs in HIV-infected individuals and is associated with HIV
      associated neurocognitive disorders (HAND). However, the mechanisms involved are
      not well understood. Previously, we showed a correlation between soluble insulin
      receptor (sIR) and HAND. Here, we investigated if binding of free insulin to sIR
      and soluble insulin-like growth factor-1 receptor (sIGF1-R) levels are associated
      with sIR in HAND. Thirty-four (34) HIV-seropositive women stratified by cognitive
      status and five HIV-seronegative women were evaluated. In a subgroup of 20 HIV
      positive and 5 donors, binding of plasma insulin to sIR was determined by ELISA
      assay of residual insulin levels in plasma immuno-depleted with anti-IR
      monoclonal antibody-Sepharose beads. sIR and sIGF1-R levels were determined by
      ELISA. Nonparametric statistics were used. Higher percentages of insulin bound to
      sIR significantly correlated with sIR levels and were associated with HAND
      status. Higher levels of plasma sIGF1-R had a positive correlation with sIR
      levels (p = 0.011) and were associated with HAND (p = 0.006). No correlations
      were observed with age, viral-immune profile, antiretroviral therapy, or TNF.
      This study suggests that changes in sIGF1-R levels and insulin binding to sIR may
      contribute to HAND.

PMID- 25604498
TI  - Comparison of bone marrow versus peripheral blood allogeneic hematopoietic stem
      cell transplantation for hematological malignancies in adults - a systematic
      review and meta-analysis.
AB  - It is still under debate whether bone marrow (BM) or peripheral blood (PB) should
      be the preferred stem cell source in adult patients undergoing allogeneic stem
      cell transplantation for hematological malignancies. After systematic literature
      search we identified nine randomised controlled trials comparing BM and PB as
      stem cell source from 2341 total hits. Meta-analysis involving 1521 patients
      showed a statistically significant reduction in overall and extensive chronic
      GvHD for patients transplanted with BM (HR 0.72; 95% CI 0.61 to 0.85 and HR 0.69;
      95% CI 0.54 to 0.9), but no difference in overall and disease-free survival. In
      the related donor setting, data from two of eight studies demonstrated a
      significant increase of relapse incidence for BM (HR 2.73; 95% CI 1.47 to 5.08).
      This systematic review demonstrates that the current clinical standard to use
      peripheral blood stem cells instead of bone marrow for allo-SCT is not inferior
      with regard to the primary outcome overall survival. 

PMID- 25604499
TI  - The inherent metastasis of leukaemia and its exploitation by sonodynamic therapy.
AB  - Nearly all cancers are linked by the inexorable phenotype of metastasis as
      malignant growths have the capability to spread from their place of origin to
      distant sites throughout the body. While different cancers may have various
      propensities to migrate towards specific locations, they are all linked by this
      unifying principal. Unlike most neoplasms, leukaemia has inherent cell motility
      as leukocytes are required to move throughout the vascular system, suggesting
      that no mutations are required for anchorage independent growth. As such, it
      seems likely that leukaemias are inherently metastatic, endowed with the
      deadliest phenotype of cancer simply due to cell of origin. This article presents
      the biology of metastasis development and how leukaemia cells are inherently
      provided these phenotypic characteristics. It is then proposed how clinicians may
      be able to exploit the motility of leukaemia and metastatic emboli of other
      cancer types through an approach known as sonodynamic therapy (SDT), a treatment
      modality that combines chemotherapeutic agents with ultrasound to preferentially
      damage malignant cells. As experimental evidence has indicated, SDT is a
      promising therapeutic approach in need of clinical testing for further
      validation. 

PMID- 25604501
TI  - Self-limiting recurrent bullous Henoch-Schonlein purpura with lupus
      anticoagulant.
AB  - Henoch-Schonlein purpura (HSP) is the most common acute systemic vasculitis of
      childhood with an incidence of approximately 1:10,000. It commonly presents with
      skin, gastrointestinal tract, joints and renal system signs and symptoms. We
      present a case of recurrent self-limiting HSP with lupus anticoagulant presenting
      with haemorrhagic bullous skin lesions and scrotal swelling. The initial
      presentation resolved within 4 weeks but over the next 6 months, a few self
      limiting but milder skin lesions occurred. Some institutions have advocated the
      use of steroids in these cases but our case showed that the use of steroids may
      not be required. This atypical presentation of HSP led to unnecessary
      investigations that this case report aims to prevent in the future by raising its
      awareness.

PMID- 25604497
TI  - The anterior commissure is a pathway for contralateral spread of herpes simplex
      virus type 1 after olfactory tract infection.
AB  - Herpes simplex encephalitis (HSE), targeting the limbic system, is the most
      common cause of viral encephalitis in the Western world. Two pathways for viral
      entry to the central nervous system (CNS) in HSE have been suggested: either via
      the trigeminal nerve or via the olfactory tract. This question remains unsettled,
      and studies of viral spread between the two brain hemispheres are scarce. Here,
      we investigated the olfactory infection as a model of infection and tropism of
      herpes simplex virus 1 (HSV-1), the causative agent of HSE, in the CNS of rats.
      Rats were instilled with HSV-1 in the right nostril and sacrificed 1-6 days post
      infection, and tissues were analysed for viral spread using immunohistochemistry
      and quantitative PCR (qPCR). After nasal instillation, HSV-1 infected mitral
      cells of the olfactory bulb (OB) on the right side only, followed by limbic
      encephalitis. As a novel finding, the anterior commissure (AC) conveyed a rapid
      transmission of virus between the right and the left OB, acting as a shortcut
      also between the olfactory cortices. The neuronal cell population that conveyed
      the viral infection via the AC was positive for the water channel protein
      aquaporin 9 (AQP9) by immunohistochemistry. Quantification of AQP9 in
      cerebrospinal fluid samples of HSE patients showed increment as compared to
      controls. We conclude that the olfactory route and the AC are important for the
      spread of HSV-1 within the olfactory/limbic system of rats and furthermore, we
      suggest that AQP9 is involved in viral tropism and pathogenesis of HSE. 

PMID- 25604502
TI  - Kikuchi-Fujimoto disease: an unusual cause of neck swelling in pregnancy.
AB  - Kikuchi-Fujimoto disease (KFD) is an unusual cause of lymphadenopathy and fever.
      Pregnancy associated with KFD presents as a diagnostic dilemma for clinicians.
      The diagnosis can be confirmed with invasive biopsies or non-invasive gene
      analysis. We report a case of a 24-year-old woman at 18 weeks' gestation with a
      neck lump and histologically confirmed KFD.

PMID- 25604503
TI  - Carcinoma of breast metastasising to mandible.
AB  - Metastatic tumours to oral cavity from distant sites are rarely seen. Bones are
      frequently involved as compared to soft tissues. Clinical presentation may vary
      according to site and size of metastatic tumour. We present a case of carcinoma
      of breast in a 50-year-old woman, metastasising to mandibular ramus, condyle and
      surrounding soft tissue structure presenting as osteomylitis of condyle. 

PMID- 25604504
TI  - Large posterior vaginal cyst in pregnancy.
AB  - A 20-year-old primigravida presented in labour with a mass protruding from her
      vagina during uterine contractions. The mass was a large tense cyst measuring 8 *
      8 cm arising from the posterior vaginal wall. The cyst was present since puberty
      but increased in size during pregnancy. It collapsed following aspiration and
      uneventful vaginal delivery was conducted. Following delivery, the cyst was
      excised and vaginal wall repaired. On histopathology the cyst was identified as a
      Mullerian cyst. The patient recovered and remained asymptomatic on follow-up.

PMID- 25604505
TI  - Yersinia adhesin A (YadA)--beauty & beast.
AB  - The trimeric autotransporter adhesin Yersinia adhesin A is the prototype of the
      type Vc secretion systems. It is expressed by enteropathogenic Yersinia
      enterocolitica and Yersinia pseudotuberculosis strains, but not by Yersinia
      pestis. A characteristic trait of YadA is its modular composition and trimeric
      nature. YadA consists of an N-terminal passenger domain which is exposed on the
      bacterial cell surface. The translocation of this passenger onto the surface is
      facilitated by a C-terminal beta-barrel domain which concomitantly anchors YadA
      into the outer membrane with three YadA monomers contributing to the formation of
      a single beta-barrel. In Y. enterocolitica, but not Y. pseudotuberculosis, YadA
      is a decisive virulence factor and its deletion renders the bacteria virtually
      avirulent in mouse models of infection. This striking importance of YadA in
      infection may derive from its manifold functions in host cell interaction.
      Presumably the most important function of YadA is that it mediates adhesion to
      extracellular matrix components of eukaryotic host cells. Only tight adhesion
      allows for the injection of "anti-host" effector proteins via a type III
      secretion system into the host cell cytosol. These effector proteins enable
      Yersinia to subvert the host immune system in order to replicate and establish
      infection. YadA is also essential for the survival of Y. enterocolitica upon
      contact with serum, an important immune-evasion mechanism called serum
      resistance. To this end, YadA interacts with several components of the host
      complement system, the first line of immune defense. This review will summarize
      recent findings about the structure and biogenesis of YadA and its interactions
      with the host complement system. 

PMID- 25604506
TI  - X-ray crystallography and its impact on understanding bacterial cell wall
      remodeling processes.
AB  - The molecular structure of matter defines its properties and function. This is
      especially true for biological macromolecules such as proteins, which participate
      in virtually all biochemical processes. A three dimensional structural model of a
      protein is thus essential for the detailed understanding of its physiological
      function and the characterization of essential properties such as ligand binding
      and reaction mechanism. X-ray crystallography is a well-established technique
      that has been used for many years, but it is still by far the most widely used
      method for structure determination. A particular strength of this technique is
      the elucidation of atomic details of molecular interactions, thus providing an
      invaluable tool for a multitude of scientific projects ranging from the
      structural classification of macromolecules over the validation of enzymatic
      mechanisms or the understanding of host-pathogen interactions to structure-guided
      drug design. In the first part of this review, we describe essential
      methodological and practical aspects of X-ray crystallography. We provide some
      pointers that should allow researchers without a background in structural biology
      to assess the overall quality and reliability of a crystal structure. To
      highlight its potential, we then survey the impact X-ray crystallography has had
      on advancing an understanding of a class of enzymes that modify the bacterial
      cell wall. A substantial number of different bacterial amidase structures have
      been solved, mostly by X-ray crystallography. Comparison of these structures
      highlights conserved as well as divergent features. In combination with
      functional analyses, structural information on these enzymes has therefore proven
      to be a valuable template not only for understanding their mechanism of
      catalysis, but also for targeted interference with substrate binding. 

PMID- 25604507
TI  - Myocardial perfusion imaging is an effective screening test for coronary artery
      disease in liver transplant candidates.
AB  - A reliable screening test for coronary artery disease (CAD) in liver transplant
      (LT) candidates with end-stage liver disease is essential because a high
      percentage of perioperative mortality and morbidity is CAD-related. In this
      study, the effectiveness of myocardial perfusion imaging (MPI) for identification
      of significant CAD in LT candidates was evaluated. Records of 244 patients
      meeting criteria for MPI were evaluated: 74 met inclusion criteria; 40 had a
      positive MPI and cardiology follow-up; 27 had a negative MPI and underwent LT;
      and seven had a negative MPI and then had coronary angiography or a significant
      cardiac event. A selective MPI interpretation strategy was established where MPI
      positive patients were divided into high, intermediate, and low CAD risk groups.
      The overall incidence of CAD in this study population was 5.1% and our strategy
      resulted in PPV 20%, NPV 94%, sensitivity 80%, and specificity 50% for
      categorizing CAD risk. When applied only to the subset of patients categorized as
      high CAD risk, the strategy was more effective, with PPV 67%, NPV 97%,
      sensitivity 80%, and specificity 94%. We determined that renal dysfunction was an
      independent predictive factor for CAD (p < 0.0001, odds ratio = 8.1), and grades
      of coronary occlusion correlated significantly with chronic renal dysfunction (p
      = 0.0079). 

PMID- 25604508
TI  - Inhibition of IL-6 signaling significantly reduces primary tumor growth and
      recurrencies in orthotopic xenograft models of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human tumors,
      with radical surgical resection as the only curative treatment option. However,
      resection is only possible in a small fraction of patients, and about 80% of the
      patients develop recurrencies. PDAC development is facilitated by the cytokine
      interleukin-6 (IL-6), which acts via classic and trans-signaling. Both pathways
      are inhibited by the anti-IL-6-receptor antibody tocilizumab, whereas the fusion
      protein sgp130Fc specifically blocks trans-signaling. Here, we show that
      conservative or adjuvant therapy with both inhibitors reduces tumor growth in an
      orthotopic model of human Colo357 cells in SCID/bg mice. In the conservative
      setting, median primary tumor weight was reduced 2.4-fold for tocilizumab and 4.4
      fold for sgp130Fc. sgp130Fc additionally led to a decrease in microvessel
      density, which was not observed with tocilizumab. In the adjuvant therapeutic
      setting after surgical resection of the primary tumor, treatment with tocilizumab
      or sgp130Fc decreased the local recurrence rate from 87.5% in the control group
      to 62.5 or 50%, respectively. Furthermore, the median weight of the local
      recurrent tumors was clearly diminished, and both inhibitors reduced the number
      of distant metastases. A significant reduction of tumor weight and metastases
      comparable to gemcitabine treatment-was also observed with both inhibitors in
      another model using the poorly differentiated PancTuI cells. Our findings
      demonstrate the inhibition of IL-6 as a new treatment option in PDAC. 

PMID- 25604509
TI  - Two-stage designs in bioequivalence trials.
AB  - PURPOSE: The aim of this study is to assess the current status of non-fixed
      sample size designs in bioequivalence trials with a focus on two-stage adaptive
      approaches. METHODS: We searched PubMed and Google Scholar from inception to
      October 2014. Regulatory guidelines were obtained from the public domain.
      Different methods were compared by Monte Carlo simulations for their impact on
      the patient's and producer's risks. RESULTS: Add-on designs, group sequential
      designs and adaptive two-stage sequential designs are currently accepted to
      demonstrate bioequivalence in various regulations. All three approaches may
      inflate the patient's risk if applied inconsiderately. Direct transfer of methods
      developed for superiority testing to bioequivalence is not warranted. Published
      two-stage frameworks maintain the type I error and generally the desired power.
      Adaptation based on the observed T/R ratio observed in the first stage should be
      applied with caution. Monte Carlo simulations are an efficient tool to explore
      the operating characteristics of methods. CONCLUSIONS: Validated two-stage
      frameworks can be applied without requiring the sponsor to perform own
      simulations-which could further improve power based on additional assumptions.
      Two-stage designs are both ethical and economical alternatives to fixed sample
      designs.

PMID- 25604511
TI  - Erratum to: flupirtine-induced liver injury--seven cases from the Berlin Case
      Control Surveillance Study and review of the German spontaneous adverse drug
      reaction reporting database.

PMID- 25604510
TI  - Linezolid-related haematological toxicity in a peritoneal dialysis patient: the
      role of therapeutic drug monitoring.

PMID- 25604512
TI  - Erratum to: Interactome analysis reveals versatile functions of Arabidopsis COLD
      SHOCK DOMAIN PROTEIN 3 in RNA processing within the nucleus and cytoplasm.

PMID- 25604513
TI  - Academic buoyancy, student's achievement, and the linking role of control: A
      cross-lagged analysis of high school students.
AB  - BACKGROUND: Previous research has indicated that although academic buoyancy and
      student's achievement are associated, the relationship is relatively modest.
      AIMS: We sought to determine whether another construct might link academic
      buoyancy and student's achievement. Based on prior theoretical and empirical
      work, we examined a sense of control as one possible linking mechanism. SAMPLE:
      The study analysed data from 2,971 students attending 21 Australian high schools.
      METHODS: We conducted a cross-lagged panel design as a first means of
      disentangling the relative salience of academic buoyancy, control, and
      achievement (Phase 1). Based upon these results, we proceeded with follow-up
      analyses of an ordered process model linking the constructs over time (Phase 2).
      RESULTS: Findings showed that buoyancy and achievement were associated with
      control over time, but not with one another (Phase 1). In addition, control
      appeared to play a role in how buoyancy influenced achievement and that a
      cyclical process may operate among the three factors over time (Phase 2).
      CONCLUSION: The findings suggest that control may play an important role in
      linking past experiences of academic buoyancy and achievement to subsequent
      academic buoyancy and achievement.

PMID- 25604514
TI  - Evaluating service delivery.

PMID- 25604515
TI  - Academic psychiatry - extinction or adaptation to a changing world: a view from
      clinical psychology.

PMID- 25604516
TI  - Artificial phrenoesophageal ligament. An experimental study in dogs.
AB  - This report deals with the preparation of a 'true' artificial phrenoesophageal
      ligament aimed at restoring effective anchoring of the esophagus to the
      diaphragm, keeping the esophagogastric sphincter in the abdomen. A total of 24
      mongrel dogs were assigned to four groups: (i) Group I (n = 4): the esophageal
      diaphragm hiatus left wide open; (ii) Group II (n = 8): the anterolateral
      esophagus walls were attached to the diaphragm by the artificial ligament and the
      esophageal hiatus was left wide opened; (iii) Group III (n = 5): in addition to
      the use of the artificial ligament, the esophageal hiatus was narrowed with two
      retroesophageal stitches; (iv) Group IV (n = 7): the only procedure was the
      esophageal hiatus narrowing with two retroesophageal stitches. The
      phrenoesophagogastric connections were released, sparing the vagus nerves. Five
      animals of groups III and IV, which did not develop hiatal hernia, were submitted
      to esophageal manometry immediately before and 15 days after surgery. In group I,
      all animals developed huge sliding hiatal hernias. In group II, two dogs (25%)
      had a paraesophageal hernia between the two parts of the artificial ligament. In
      group III, neither sliding hiatal hernia nor paraesophageal hernia occurred. In
      group IV, two animals (28.6%) developed sliding esophageal hiatus hernia.
      Regarding esophageal manometry, postoperative significant difference between
      groups III and IV (P = 0.008) was observed. Thus, the artificial phrenoesophageal
      ligament maintained the esophagus firmly attached to the diaphragm in all animals
      and the esophagogastric sphincter pressure was significantly higher in this
      group. 

PMID- 25604518
TI  - Efficacy and adverse effects of drugs used to treat adult cystic fibrosis.
AB  - INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease and is the
      most commonly seen monogenetic disease in Caucasians. The disease has various
      manifestations resulting from the abnormal thick secretions, most common being
      chronic lung infection and airway obstruction. Many new promising drugs have
      appeared on the horizon over the years. This review here is an attempt to bring
      together the various treatments being used to prolong and enhance the quality of
      life of CF patients. AREAS COVERED: A literature review of published as well as
      ongoing clinical trials, meta-analysis and systematic reviews regarding the drugs
      used in CF management was carried out using PubMed and Ovid databases. EXPERT
      OPINION: New concepts have been formed and some positive results in this
      direction have already led to the approval of cystic fibrosis transmembrane
      conductance regulator potentiator drug. Gene therapy and stem cell therapy are
      under development. The current therapies such as dornase alfa and pancreatic
      enzymes targeting the symptoms continue to evolve as they play an important
      complementary role. Development of new simple and cost-effective markers, which
      help assess the efficacy and safety of these constantly emerging new drugs, is
      also being investigated.

PMID- 25604517
TI  - Multiplex PCR for detection of virulence markers of Vibrio vulnificus.
AB  - Vibrio vulnificus is a Gram-negative pathogen found in coastal and estuarine
      waters worldwide that can cause life threatening diseases. Characterization of
      the vcg (virulence correlated gene) or 16S rRNA alleles is used to distinguish
      virulent (clinical (C)-type) from presumably avirulent (environmental (E)-type)
      strains. However, some studies reported a significant number of clinical strains
      belonging to the E-type. In recent years more potential virulence markers have
      been identified, that are useful for the identification of potentially pathogenic
      isolates of the E-type. In this study, we successfully combined detection of
      pathogenicity region XII, nanA and a mannitol fermentation operon with the
      virulence associated alleles of the 16S rRNA and vcg genes in one multiplex PCR.
      Additionally, toxR primers for species confirmation and internal amplification
      control were included. Validation of multiplex amplification was performed with a
      total of 132 bacterial strains, including V. vulnificus (n = 71), other
      Vibrionaceae (n = 50) and non-Vibrio isolates (n = 11). Multiplex PCR showed
      reliable amplification of four of the five virulence markers with a high
      sensitivity and specificity. Amplification of the 16S rRNA type B allele was not
      completely reliable with conventional PCR assays, however, the positive
      predictive value of this marker was 100 %. SIGNIFICANCE AND IMPACT OF THE STUDY:
      A multiplex PCR for simultaneous detection and characterization of potentially
      virulent strains of Vibrio vulnificus was developed and validated. Monitoring
      programs will benefit from this cost and time effective method when screening
      large strain collections. Application of the multiplex PCR simplifies
      determination of risks emanating from V. vulnificus in recreational waters or
      mussel primary production.

PMID- 25604519
TI  - Electrostatic interaction on loading of therapeutic peptide GLP-1 into porous
      silicon nanoparticles.
AB  - Porous silicon (PSi) nanoparticles' tunable properties are facilitating their use
      at highly challenging medical tasks such as peptide delivery. Because of many
      different mechanisms that are affecting the interaction between the peptide and
      the particle, the drug incorporation into the mesoporous delivery system is not
      straightforward. We have studied the adsorption and loading of incretin hormone
      glucagon like peptide 1 (GLP-1) on PSi nanoparticles. The results show that the
      highest loading degree can be achieved in pH values near the isoelectric point of
      peptide, and the phenomenon is independent of the surface's zeta potential. In
      order to study the interaction between the peptide and the nanoparticle, we
      studied the adsorption with lower concentrations and noticed that also non
      Coulombic forces have a big role in adsorption of GLP-1. Adsorption is effective
      and pH-independent especially on low peptide concentrations and onto more
      hydrophobic nanoparticles. Reversibility of adsorption was studied as a function
      of buffer pH. When the loading is compared to the total mass of the formulation,
      the loading degree is 29%, and during desorption experiments 25% is released in 4
      h and can be considered as a reversible loading degree. Thus, the peptides
      adsorbed first seem to create irreversibly adsorbed layer that facilitates
      reversible adsorption of following peptides. 

PMID- 25604520
TI  - Earned media and public engagement with CDC's "Tips from Former Smokers"
      campaign: an analysis of online news and blog coverage.
AB  - BACKGROUND: In March 2012, the US Centers for Disease Control and Prevention
      (CDC) launched the first-ever paid national tobacco education campaign. At a cost
      of US $54 million, "Tips from Former Smokers" (Tips) ran for 3 months across
      multiple media, depicting the suffering experienced by smokers and their families
      in graphic detail. The potential impact and reach of the Tips campaign was not
      limited to that achieved through paid media placements. It was also potentially
      extended through "earned media", including news and blog coverage of the
      campaign. Such coverage can shape public understanding of and facilitate public
      engagement with key health issues. OBJECTIVE: To better understand the
      contribution of earned media to the public's engagement with health issues in the
      current news media environment, we examined the online "earned media" and public
      engagement generated by one national public health campaign. METHODS: We
      constructed a purposive sample of online media coverage of the CDC's 2012 Tips
      from Former Smokers television campaign, focusing on 14 influential and
      politically diverse US news outlets and policy-focused blogs. We identified
      relevant content by combining campaign and website-specific keywords for 4 months
      around the campaign release. Each story was coded for content, inclusion of
      multimedia, and measures of audience engagement. RESULTS: The search yielded 36
      stories mentioning Tips, of which 27 were focused on the campaign. Story content
      between pieces was strikingly similar, with most stories highlighting the same
      points about the campaign's content, cost, and potential impact. We saw notable
      evidence of audience engagement; stories focused on Tips generated 9547 comments,
      8891 Facebook "likes", 1027 tweets, and 505 story URL shares on Facebook.
      Audience engagement varied by story and site, as did the valence and relevance of
      associated audience comments. Comments were most oppositional on CNN and most
      supportive on Yahoo. Comment coding revealed approximately equal levels of
      opposition and support overall. We identified four common arguments among
      oppositional comments: government intrusion on personal behaviors, problematic
      allocation of governmental spending, questionable science, and challenges
      regarding campaign efficacy. Supportive comments tended to convey personal
      stories and emotions. CONCLUSIONS: The Tips campaign received limited coverage on
      either online news or blog sources, but the limited number of stories generated
      engagement among online audiences. In addition to the content and volume of blog
      and news coverage, audience comments and websites' mechanisms for sharing stories
      via social media are likely to determine the influence of online earned media. In
      order to facilitate meaningful evaluation of public health campaigns within the
      rapidly advancing media environment, there is a need for the public health
      community to build consensus regarding collection and assessment of engagement
      data.

PMID- 25604521
TI  - Nonstrangulating intestinal infarction associated with Strongylus vulgaris in
      referred Danish equine cases.
AB  - REASONS FOR PERFORMING STUDY: Strongylus vulgaris is a pathogenic helminth
      parasite infecting horses and was once considered to be the primary cause of
      colic. Migrating larvae cause ischaemia and infarction of intestinal segments.
      This knowledge is derived from case reports and experimental inoculations of
      parasite-naive foals, and it remains unknown to what extent the parasite is
      associated with different types of colic. OBJECTIVES: To evaluate the role of S.
      vulgaris as a risk factor for different types of colic in horses. STUDY DESIGN: A
      retrospective case-control study among horses referred with abdominal pain to the
      University of Copenhagen Large Animal Teaching Hospital during 2009-2011.
      METHODS: Each colic case was matched with an equid of the same type (pony,
      Warmblooded or Coldblooded), age, sex and admitted in the same month and year but
      for problems unrelated to the gastrointestinal tract. Serum samples were analysed
      for antibodies to migrating S. vulgaris larvae using a recently developed enzyme
      linked immunosorbent assay (ELISA). The following 4 case definitions were used:
      colic sensu lato, i.e. all horses presenting with colic (n = 274), with further
      subgroups, i.e. undiagnosed colics (n = 48), strangulating obstructions (n = 76)
      and nonstrangulating infarctions (n = 20). RESULTS: Strongylus vulgaris antibody
      levels were similar to control values in colics sensu lato and horses with
      undiagnosed colic. In contrast, nonstrangulating intestinal infarctions were
      significantly associated with positive S. vulgaris ELISAs (odds ratio 5.33, 95%
      confidence interval 1.03-27.76, P = 0.05). Also, horses with nonstrangulating
      infarctions had a significantly higher occurrence of positive ELISAs than horses
      with strangulating obstructions (odds ratio 3.79, 95% confidence interval 1.34
      10.68, P = 0.01) and the colic sensu lato group (odds ratio 3.09, 95% confidence
      interval 1.20-8.01, P = 0.02). CONCLUSIONS: Nonstrangulating intestinal
      infarction was strongly associated with S. vulgaris-specific antibodies, whereas
      the more broadly defined colic categories were not associated with positive ELISA
      results. Thus, the ELISA holds potential to become a helpful adjunct in diagnosis
      and management of horses with colic.

PMID- 25604522
TI  - Highly sensitive fluorescence biosensors for sparfloxacin detection at nanogram
      level based on electron transfer mechanism of cadmium telluride quantum dots.
AB  - A sensitive fluorescence biosensor for determining sparfloxacin (SPF) based on
      the electron transfer mechanism and the fluorescence quenching effect of SPF to
      cadmium telluride quantum dots (CdTe QDs) was developed. The mechanism of the
      interaction between SPF and CdTe QDs was investigated by UV/Vis absorption and
      fluorescence spectroscopy. The biosensor could be used for the determination of
      SPF with a high sensitivity. Under optimum conditions, the linear range was from
      0.28 to 40 MUg SPF ml(-1) with a correlation coefficient of 0.9983, and the
      detection limit (3delta/k) was 83.7 ng SPF ml(-1). Furthermore, this method has
      been applied to the determination of SPF in the synthetic environmental water
      samples and the spiked human serum samples with good results.

PMID- 25604523
TI  - Microbial production of lactic acid.
AB  - Lactic acid is an important commodity chemical having a wide range of
      applications. Microbial production effectively competes with chemical synthesis
      methods because biochemical synthesis permits the generation of either one of the
      two enantiomers with high optical purity at high yield and titer, a result which
      is particularly beneficial for the production of poly(lactic acid) polymers
      having specific properties. The commercial viability of microbial lactic acid
      production relies on utilization of inexpensive carbon substrates derived from
      agricultural or waste resources. Therefore, optimal lactic acid formation
      requires an understanding and engineering of both the competing pathways involved
      in carbohydrate metabolism, as well as pathways leading to potential by-products
      which both affect product yield. Recent research leverages those biochemical
      pathways, while researchers also continue to seek strains with improved tolerance
      and ability to perform under desirable industrial conditions, for example, of pH
      and temperature. 

PMID- 25604525
TI  - Trends in magnetism of free Rh clusters via relativistic ab-initio calculations.
AB  - A fully relativistic ab-initio study on free Rh clusters of 13-135 atoms is
      performed to identify general trends concerning their magnetism and to check
      whether concepts which proved to be useful in interpreting magnetism of 3d metals
      are applicable to magnetism of 4d systems. We found that there is no systematic
      relation between local magnetic moments and coordination numbers. On the other
      hand, the Stoner model appears well-suited both as a criterion for the onset of
      magnetism and as a guide for the dependence of local magnetic moments on the site
      resolved density of states at the Fermi level. Large orbital magnetic moments
      antiparallel to spin magnetic moments were found for some sites. The intra-atomic
      magnetic dipole Tz term can be quite large at certain sites but as a whole it is
      unlikely to affect the interpretation of x-ray magnetic circular dichroism
      experiments based on the sum rules.

PMID- 25604524
TI  - Qualitative differences in brain-infiltrating T cells are associated with a fatal
      outcome in mice infected with Japanese encephalitis virus.
AB  - Japanese encephalitis (JE) is the most important form of viral encephalitis in
      Asia. The critical factors determining mortality and severity of JE virus (JEV)
      infection remain unclear. We identified brain-infiltrating T cells associated
      with a fatal outcome of JEV infection in mice. Dying mice were defined as those
      that lost more than 25 % of their body weight by day 13 and died by day 21, while
      surviving mice were defined as those that lost less than 10 % by day 13, based on
      the result of the survival time course study. Two groups of five mice that
      demonstrated brain virus titers of >1 * 10(6) pfu/g were randomly selected from
      the dying and surviving groups and used in the analyses. Cytokine patterns in
      brains were first examined, revealing a higher ratio of Th1-related cytokine
      genes in dying mice. The expression levels of CD3, CD8, CD25, and CD69 increased
      in JEV-infected mice relative to mock-infected mice. However, expression levels
      of these cell-surface markers did not differ between the two groups. T-cell
      receptor (TCR) usage and complementary determining region 3 (CDR3) sequences were
      analyzed in the brain-infiltrating T cells. T cells expressing VA8-1, VA10-1, and
      VB2-1 increased in both groups. However, the dominant T-cell clones as defined by
      CDR3 amino acid sequence differed between the two groups. The results indicate
      that the outcome of JEV infection, death or survival, was determined by
      qualitative differences in infiltrating T-cell clones with unique CDR3 amino acid
      sequences.

PMID- 25604526
TI  - Time trends in leisure time physical activity and physical fitness in the
      elderly: five-year follow-up of the Spanish National Health Survey (2006-2011).
AB  - OBJECTIVES: To estimate the trends in the practice of leisure time physical
      activity, walking up 10 steps, and walking for 1h, during the years 2006-2011, in
      elderly Spanish people. STUDY DESIGN: Observational study, retrospective analysis
      of Spanish National Health Surveys. We analysed data collected from the Spanish
      National Health Surveys conducted in 2006 (n=30,072) and 2011 (n=21,007), through
      self-reported information. The number of subjects aged >=65 years included in the
      current study was n=5756 in 2006 (19.14%) and n=4617 in 2011 (21.97%). We
      included responses from adults aged 65 years and older. OUTCOME MEASURES: The
      main variables included leisure-time physical activity, walking up 10 steps, and
      walking for 1h. We analysed socio-demographic characteristics, individuals' self
      rated health status, lifestyle habits, co-morbid conditions and disability using
      multivariable logistic regression models. RESULTS: The total number of subjects
      was 10,373 (6076 women, 4297 men). The probability of self-reported capacity was
      significantly higher in 2006 than in 2011 for leisure-time physical activity,
      walking up 10 steps, and walking for 1h for both sexes (women: OR 2.20, 95%IC
      1.91-5.55; OR 2.50, 95%IC 1.99-3.14; OR 1.04, 95%IC 1.01-1.07; men: OR 2.20,
      95%IC 1.91-2.55; OR 2.01, 95%IC 1.40-2.89; OR 1.05, 95%IC 1.0-1.1) respectively.
      Both sexes were associated with a significantly lower probability of performing
      leisure-time physical activity, walking up 10 steps, and walking for 1h.
      Additionally, those over 80 years of age, on average, showed a poor or very poor
      perception of their health and presented with some type of disability.
      CONCLUSION: A decrease in the proportion of respondents who self-reported
      undertaking leisure-time physical activity, walking up 10 steps, and walking for
      1h was observed in the Spanish population of over 65 years between 2006 and 2011.

PMID- 25604527
TI  - Benign leiomyoma or malignant sarcoma: the difficult differential diagnosis.

PMID- 25604528
TI  - How does information reduce psychological impact?

PMID- 25604529
TI  - Response to "Leptin disturbance probably involved in the pathogenesis of obesity
      induced depressive symptoms".

PMID- 25604530
TI  - GROWTH REGULATING FACTOR5 stimulates Arabidopsis chloroplast division,
      photosynthesis, and leaf longevity.
AB  - Arabidopsis (Arabidopsis thaliana) leaf development relies on subsequent phases
      of cell proliferation and cell expansion. During the proliferation phase,
      chloroplasts need to divide extensively, and during the transition from cell
      proliferation to expansion, they differentiate into photosynthetically active
      chloroplasts, providing the plant with energy. The transcription factor GROWTH
      REGULATING FACTOR5 (GRF5) promotes the duration of the cell proliferation period
      during leaf development. Here, it is shown that GRF5 also stimulates chloroplast
      division, resulting in a higher chloroplast number per cell with a concomitant
      increase in chlorophyll levels in 35S:GRF5 leaves, which can sustain higher rates
      of photosynthesis. Moreover, 35S:GRF5 plants show delayed leaf senescence and are
      more tolerant for growth on nitrogen-depleted medium. Cytokinins also stimulate
      leaf growth in part by extending the cell proliferation phase, simultaneously
      delaying the onset of the cell expansion phase. In addition, cytokinins are known
      to be involved in chloroplast development, nitrogen signaling, and senescence.
      Evidence is provided that GRF5 and cytokinins synergistically enhance cell
      division and chlorophyll retention after dark-induced senescence, which suggests
      that they also cooperate to stimulate chloroplast division and nitrogen
      assimilation. Taken together with the increased leaf size, ectopic expression of
      GRF5 has great potential to improve plant productivity.

PMID- 25604531
TI  - Small heat shock proteins can release light dependence of tobacco seed during
      germination.
AB  - Small heat shock proteins (sHSPs) function as ATP-independent molecular
      chaperones, and although the production and function of sHSPs have often been
      described under heat stress, the expression and function of sHSPs in fundamental
      developmental processes, such as pollen and seed development, have also been
      confirmed. Seed germination involves the breaking of dormancy and the resumption
      of embryo growth that accompany global changes in transcription, translation, and
      metabolism. In many plants, germination is triggered simply by imbibition of
      water; however, different seeds require different conditions in addition to
      water. For small-seeded plants, like Arabidopsis (Arabidopsis thaliana), lettuce
      (Lactuca sativa), tomato (Solanum lycopersicum), and tobacco (Nicotiana tabacum),
      light is an important regulator of seed germination. The facts that sHSPs
      accumulate during seed development, sHSPs interact with various client proteins,
      and seed germination accompanies synthesis and/or activation of diverse proteins
      led us to investigate the role of sHSPs in seed germination, especially in the
      context of light dependence. In this study, we have built transgenic tobacco
      plants that ectopically express sHSP, and the effect was germination of the seeds
      in the dark. Administering heat shock to the seeds also resulted in the
      alleviation of light dependence during seed germination. Subcellular localization
      of ectopically expressed sHSP was mainly observed in the cytoplasm, whereas heat
      shock-induced sHSPs were transported to the nucleus. We hypothesize that
      ectopically expressed sHSPs in the cytoplasm led the status of cytoplasmic
      proteins involved in seed germination to function during germination without
      additional stimulus and that heat shock can be another signal that induces seed
      germination. 

PMID- 25604534
TI  - Deciphering the insights of poly(ADP-ribosylation) in tumor progression.
AB  - Poly (ADP-ribose) polymerase (PARP) inhibitors are particularly efficient against
      tumors with defects in the homologous recombination repair pathway. Nonetheless
      poly(ADP-ribosylation) (PARylation) modulates prometastasic activities and
      adaptation of tumor to a hostile microenvironment. Modulation of metastasis
      promoting traits is possible through the alteration of key transcription factors
      involved in the regulation of the hypoxic response, the recruitment of new
      vessels (or angiogenesis), and the stimulation of epithelial to mesenchymal
      transition (EMT). In this review, we summarized some of the findings that
      focalize on PARP-1's action on tumor aggressiveness, suggesting new therapeutic
      opportunities against an assembly of tumors not necessarily bearing DNA repair
      defects. Metastasis accounts for the vast majority of mortality derived from
      solid cancer. PARP-1 is an active player in tumor adaptation to metastasis and
      PARP inhibitors, recognized as promising therapeutic agents against homologous
      recombination deficient tumors, has novel properties responsible for the
      antimetastatic actions in different tumor settings. 

PMID- 25604532
TI  - Leaf responses to mild drought stress in natural variants of Arabidopsis.
AB  - Although the response of plants exposed to severe drought stress has been studied
      extensively, little is known about how plants adapt their growth under mild
      drought stress conditions. Here, we analyzed the leaf and rosette growth response
      of six Arabidopsis (Arabidopsis thaliana) accessions originating from different
      geographic regions when exposed to mild drought stress. The automated phenotyping
      platform WIWAM was used to impose stress early during leaf development, when the
      third leaf emerges from the shoot apical meristem. Analysis of growth-related
      phenotypes showed differences in leaf development between the accessions. In all
      six accessions, mild drought stress reduced both leaf pavement cell area and
      number without affecting the stomatal index. Genome-wide transcriptome analysis
      (using RNA sequencing) of early developing leaf tissue identified 354 genes
      differentially expressed under mild drought stress in the six accessions. Our
      results indicate the existence of a robust response over different genetic
      backgrounds to mild drought stress in developing leaves. The processes involved
      in the overall mild drought stress response comprised abscisic acid signaling,
      proline metabolism, and cell wall adjustments. In addition to these known severe
      drought-related responses, 87 genes were found to be specific for the response of
      young developing leaves to mild drought stress. 

PMID- 25604535
TI  - Nanoscale magnetic stirring bars for heterogeneous catalysis in microscopic
      systems.
AB  - Nanometer-sized magnetic stirring bars containing Pd nanoparticles (denoted as
      Fe3 O4 -NC-PZS-Pd) for heterogeneous catalysis in microscopic system were
      prepared through a facile two-step process. In the hydrogenation of styrene, Fe3
      O4 -NC-PZS-Pd showed an activity similar to that of the commercial Pd/C catalyst,
      but much better stability. In microscopic catalytic systems, Fe3 O4 -NC-PZS-Pd
      can effectively stir the reaction solution within microdrops to accelerate mass
      transfer, and displays far better catalytic activity than the commercial Pd/C for
      the hydrogenation of methylene blue in an array of microdroplets. These results
      suggested that the Fe3 O4 -NC-PZS-Pd could be used as nanoscale stirring bars in
      nanoreactors. 

PMID- 25604536
TI  - [New goal: the impact factor].

PMID- 25604533
TI  - Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic
      Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association
      Study.
AB  - OBJECTIVE: Takayasu arteritis is a rare large vessel vasculitis with incompletely
      understood etiology. This study was undertaken to perform the first unbiased
      genome-wide association analysis of Takayasu arteritis. METHODS: Two independent
      cohorts of patients with Takayasu arteritis from Turkey and North America were
      included in our study. The Turkish cohort consisted of 559 patients and 489
      controls, and the North American cohort consisted of 134 patients and 1,047
      controls of European ancestry. Genotyping was performed using the Omni1-Quad and
      Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality
      control measures and subsequently analyzed to discover genetic susceptibility
      loci for Takayasu arteritis. RESULTS: We identified genetic susceptibility loci
      for Takayasu arteritis with a genome-wide level of significance in IL6
      (rs2069837) (odds ratio [OR] 2.07, P = 6.70 * 10(-9)), RPS9/LILRB3 (rs11666543)
      (OR 1.65, P = 2.34 * 10(-8)), and an intergenic locus on chromosome 21q22
      (rs2836878) (OR 1.79, P = 3.62 * 10(-10)). The genetic susceptibility locus in
      RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome
      19q13.4, and the disease risk variant in this locus correlates with reduced
      expression of multiple genes including the inhibitory leukocyte immunoglobulin
      like receptor gene LILRB3 (P = 2.29 * 10(-8)). In addition, we identified
      candidate susceptibility genes with suggestive levels of association (P < 1 * 10(
      5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B.
      CONCLUSION: Our findings indicate novel genetic susceptibility loci for Takayasu
      arteritis and uncover potentially important aspects of the pathophysiology of
      this form of vasculitis.

PMID- 25604537
TI  - [Treatment of the human body : the possibilities and limits of plastic surgery].
AB  - The desire for authenticity is often cited as a motive for making use of plastic
      surgery. This article aims to elaborate on the meaning of this particular
      authenticity. At the same time, it discusses reasons that justify or forbid a
      plastic surgery intervention in the light of ethics. For this purpose, a
      distinction is made between "objective body" (Korper) and "subjective body"
      (Leib), and the objectives of medical actions are questioned. Through the
      terminological differentiation between integrity (Integritat), prosperity
      (Wohlergehen), and well-being (Wohlbefinden), these objectives are qualified and
      the limits of medical actions are determined. 

PMID- 25604538
TI  - [New aspects in reconstructive nasal surgery].
AB  - Developments in surgical procedures have led to improved results in the field of
      reconstructive nasal surgery. In this article, the authors focus on the forehead
      flap technique in one of its smallest forms to cover three-layered alar defects.
      The example of a complete nasal reconstruction shows how, despite the use of a
      proven surgical concept, serious complications could occur. In the case shown, a
      satisfactory outcome was achieved by starting anew with the forehead flap in one
      of the largest forms-the expanded lateral forehead flap. The authors ascribe
      particular importance to preoperative analysis with standardized series of
      photographs. Such series should be made before each surgical step. These are
      indispensable for structured planning and, thus, are prerequisite for an
      excellent outcome. 

PMID- 25604539
TI  - [Multiple aphthous lesions of the oral mucosa].

PMID- 25604540
TI  - Rheological, physical, and sensory attributes of gluten-free rice cakes
      containing resistant starch.
AB  - In this study the effect of resistant starch (RS) addition on gluten-free cakes
      from rice flour and tapioca starch physical and sensorial properties was
      investigated. Increase in RS concentration made cake batters less elastic (drop
      of G'(omega), G''(omega) values) and thinner (viscosity decreased). Cakes
      specific volume increased with an increase in RS level and was maximized for 15
      g/100 g RS, although porosity values were significantly unaffected by RS content.
      Crumb grain analysis exhibited a decrease in surface porosity, number of pores
      and an increase in average pore diameter as RS concentration increased. During
      storage, cake crumb remained softer in formulations with increasing amounts of
      RS. Sensory evaluation of cakes demonstrated the acceptance of all formulations,
      with cake containing 20 g/100 g RS mostly preferred. Gluten-free cakes with
      improved quality characteristics and high nutritional value can be manufactured
      by the incorporation of RS. 

PMID- 25604541
TI  - A decision ladder analysis of eco-driving: the first step towards fuel-efficient
      driving behaviour.
AB  - This paper provides a decision ladder analysis of eco-driving, and a discussion
      of the resultant models in terms of the skills, rules and knowledge taxonomy of
      human behaviour and how this can inform the design of an in-vehicle, eco-driving
      support system. In order to understand the types of behaviours that characterise
      fuel-efficient driving, a review was conducted of the academic literature and of
      more publicly available resources, such as governmental, car manufacturers' and
      specific eco-driving organisations' websites. The review identified four largely
      distinct driving activities that play a central role in the use of fuel in the
      private road vehicle. A focus group involving four researchers in the transport
      ergonomics field, followed by a series of five interviews with eco-driving
      experts, served to validate, supplement and further specify the models.
      Practitioner Summary: This paper presents a decision ladder analysis of eco
      driving. A four-member focus group and five interviews with eco-driving experts
      were conducted; the resultant models are discussed in terms of supporting fuel
      efficient driving behaviours in the novice eco-driver through their potential to
      inform the design of an in-vehicle eco-driving support system. 

PMID- 25604542
TI  - Prevalence and association of self-reported anxiety, pain, and oral
      parafunctional habits with temporomandibular disorders in Japanese children and
      adolescents: a cross-sectional survey.
AB  - BACKGROUND: Associations between temporomandibular disorder (TMD) and
      psychological variables, pain conditions, and daily activities have been reported
      more commonly in middle-aged individuals than in children. However, to determine
      factor-specific preventive programs for TMD, it is important to evaluate the
      associations between multiple factors and TMD symptoms during childhood. The aim
      of this study was to assess the relationship between TMD symptoms and other
      orofacial pain conditions, daily activities, and trait anxiety in a population
      based cross-sectional survey of Japanese children and adolescents. METHODS: A
      total of 1,415 subjects (11-15 years old) self-reported their TMD symptoms,
      headache, neck pain, and toothache, and completed questionnaire scales that
      assessed 15 daily activities. Trait anxiety was assessed using the State Trait
      Anxiety Inventory for Children-Trait (STAIC-T) scale. Subjects were dichotomized
      into a TMD group or control group, based on whether they reported at least 1 TMD
      symptom: the TMD group (>=1 TMD symptom, n = 182) and the control group (no TMD
      symptoms, n = 1,233). Data were analyzed using the chi-square test and
      multivariate logistic regression analysis. RESULTS: The prevalence rates for
      headache and neck pain were significantly higher in the TMD group than in the
      control group (44.0% vs. 24.7% and 54.4% vs. 30.0%, respectively; both P <
      0.001). The odds ratios for TMD symptoms in subjects with neck pain and frequent
      diurnal clenching were 2.08 (P < 0.001) and 3.69 (P = 0.011), respectively.
      Moreover, high STAIC-T scores were weakly associated with TMD symptoms.
      CONCLUSIONS: In this young Japanese population, TMD symptoms were associated with
      other orofacial pain conditions, particularly neck pain, although they were only
      weakly associated with trait anxiety. Diurnal clenching was strongly associated
      with TMD symptoms. Health professionals should carefully consider these factors
      when developing appropriate management strategies for TMD in children and
      adolescents.

PMID- 25604543
TI  - Incidentally detected large idiopathic brachial artery aneurysm: a potentially
      life-threatening discovery.

PMID- 25604544
TI  - Monte Carlo simulation of radiation transport in human skin with rigorous
      treatment of curved tissue boundaries.
AB  - In three-dimensional (3-D) modeling of light transport in heterogeneous
      biological structures using the Monte Carlo (MC) approach, space is commonly
      discretized into optically homogeneous voxels by a rectangular spatial grid. Any
      round or oblique boundaries between neighboring tissues thus become serrated,
      which raises legitimate concerns about the realism of modeling results with
      regard to reflection and refraction of light on such boundaries. We analyze the
      related effects by systematic comparison with an augmented 3-D MC code, in which
      analytically defined tissue boundaries are treated in a rigorous manner. At
      specific locations within our test geometries, energy deposition predicted by the
      two models can vary by 10%. Even highly relevant integral quantities, such as
      linear density of the energy absorbed by modeled blood vessels, differ by up to
      30%. Most notably, the values predicted by the customary model vary strongly and
      quite erratically with the spatial discretization step and upon minor
      repositioning of the computational grid. Meanwhile, the augmented model shows no
      such unphysical behavior. Artifacts of the former approach do not converge toward
      zero with ever finer spatial discretization, confirming that it suffers from
      inherent deficiencies due to inaccurate treatment of reflection and refraction at
      round tissue boundaries.

PMID- 25604545
TI  - Multimodal imaging of cutaneous wound tissue.
AB  - Quantitative assessment of wound tissue ischemia, perfusion, and inflammation
      provides critical information for appropriate detection, staging, and treatment
      of chronic wounds. However, few methods are available for simultaneous assessment
      of these tissue parameters in a noninvasive and quantitative fashion. We
      integrated hyperspectral, laser speckle, and thermographic imaging modalities in
      a single-experimental setup for multimodal assessment of tissue oxygenation,
      perfusion, and inflammation characteristics. Algorithms were developed for
      appropriate coregistration between wound images acquired by different imaging
      modalities at different times. The multimodal wound imaging system was validated
      in an occlusion experiment, where oxygenation and perfusion maps of a healthy
      subject's upper extremity were continuously monitored during a postocclusive
      reactive hyperemia procedure and compared with standard measurements. The system
      was also tested in a clinical trial where a wound of three millimeters in
      diameter was introduced on a healthy subject's lower extremity and the healing
      process was continuously monitored. Our in vivo experiments demonstrated the
      clinical feasibility of multimodal cutaneous wound imaging.

PMID- 25604546
TI  - Use of hyperspectral imaging technology to develop a diagnostic support system
      for gastric cancer.
AB  - Hyperspectral imaging (HSI) is a new technology that obtains spectroscopic
      information and renders it in image form. This study examined the difference in
      the spectral reflectance (SR) of gastric tumors and normal mucosa recorded with a
      hyperspectral camera equipped with HSI technology and attempted to determine the
      specific wavelength that is useful for the diagnosis of gastric cancer. A total
      of 104 gastric tumors removed by endoscopic submucosal dissection from 96
      patients at Yamaguchi University Hospital were recorded using a hyperspectral
      camera. We determined the optimal wavelength and the cut-off value for
      differentiating tumors from normal mucosa to establish a diagnostic algorithm. We
      also attempted to highlight tumors by image processing using the hyperspectral
      camera's analysis software. A wavelength of 770 nm and a cut-off value of 1/4 the
      corrected SR were selected as the respective optimal wavelength and cut-off
      values. The rates of sensitivity, specificity, and accuracy of the algorithm's
      diagnostic capability were 71%, 98%, and 85%, respectively. It was possible to
      enhance tumors by image processing at the 770-nm wavelength. HSI can be used to
      measure the SR in gastric tumors and to differentiate between tumorous and normal
      mucosa.

PMID- 25604548
TI  - High CCR5 expression in natalizumab-associated progressive multifocal
      leukoencephalopathy immune reconstitution inflammatory syndrome supports
      treatment with the CCR5 inhibitor maraviroc.

PMID- 25604547
TI  - Amyloid beta oligomers in Alzheimer's disease pathogenesis, treatment, and
      diagnosis.
AB  - Protein aggregation is common to dozens of diseases including prionoses,
      diabetes, Parkinson's and Alzheimer's. Over the past 15 years, there has been a
      paradigm shift in understanding the structural basis for these proteinopathies.
      Precedent for this shift has come from investigation of soluble Abeta oligomers
      (AbetaOs), toxins now widely regarded as instigating neuron damage leading to
      Alzheimer's dementia. Toxic AbetaOs accumulate in AD brain and constitute long
      lived alternatives to the disease-defining Abeta fibrils deposited in amyloid
      plaques. Key experiments using fibril-free AbetaO solutions demonstrated that
      while Abeta is essential for memory loss, the fibrillar Abeta in amyloid deposits
      is not the agent. The AD-like cellular pathologies induced by AbetaOs suggest
      their impact provides a unifying mechanism for AD pathogenesis, explaining why
      early stage disease is specific for memory and accounting for major facets of AD
      neuropathology. Alternative ideas for triggering mechanisms are being actively
      investigated. Some research favors insertion of AbetaOs into membrane, while
      other evidence supports ligand-like accumulation at particular synapses. Over a
      dozen candidate toxin receptors have been proposed. AbetaO binding triggers a
      redistribution of critical synaptic proteins and induces hyperactivity in
      metabotropic and ionotropic glutamate receptors. This leads to Ca(2+) overload
      and instigates major facets of AD neuropathology, including tau
      hyperphosphorylation, insulin resistance, oxidative stress, and synapse loss.
      Because different species of AbetaOs have been identified, a remaining question
      is which oligomer is the major pathogenic culprit. The possibility has been
      raised that more than one species plays a role. Despite some key unknowns, the
      clinical relevance of AbetaOs has been established, and new studies are beginning
      to point to co-morbidities such as diabetes and hypercholesterolemia as
      etiological factors. Because pathogenic AbetaOs appear early in the disease, they
      offer appealing targets for therapeutics and diagnostics. Promising therapeutic
      strategies include use of CNS insulin signaling enhancers to protect against the
      presence of toxins and elimination of the toxins through use of highly specific
      AbetaO antibodies. An AD-dependent accumulation of AbetaOs in CSF suggests their
      potential use as biomarkers and new AbetaO probes are opening the door to brain
      imaging. Overall, current evidence indicates that Abeta oligomers provide a
      substantive molecular basis for the cause, treatment and diagnosis of Alzheimer's
      disease.

PMID- 25604552
TI  - Development and expression of maternal behavior in naive female C57BL/6 mice.
AB  - Naive female mice are usually described as spontaneously maternal. We
      investigated how many exposures to pups (15 min vs. 1 hr) were needed to induce
      full maternal behavior (FMB) in 20-22, 30-35, 60-65-days-old naive female mice
      (C57BL/6), and how cohabitation with the parturient mother and newborn siblings
      facilitated juvenile maternal behavior (MB). Only 20% of the adults displayed FMB
      immediately after the first exposure to pups. Incomplete MB was present in 11%,
      20%, and 30% of juveniles, adolescents and adults, respectively. Three-sixty
      minute exposures to pups induced FMB in all adult subjects. All naive juveniles
      that were not exposed to their siblings and maternal fluids failed to show
      maternal behavior. In contrast, more than half of the juveniles present at their
      homecage during delivery of a second litter showed incomplete MB (34.5%) or FMB
      (21.5%) when tested individually housed in a novel cage. This study suggests that
      most adult female mice are not spontaneously maternal but gradually sensitized.
      Besides, naive juveniles could be inhibited or not motivated to show MB, but
      display adult-like behavior toward pups if previously exposed to newborn siblings
      and maternal fluids.

PMID- 25604553
TI  - Routine HIV testing within the emergency department of a major trauma centre: a
      pilot study.
AB  - OBJECTIVES: UK guidelines recommend routine HIV testing for all medical
      admissions where the local prevalence exceeds 2 per 1000. We aimed to review
      uptake of HIV testing in the emergency department (ED) of one of the country's
      major trauma centres in a 3-month pilot study (March-June 2013). METHODS: ED
      attendees already having blood tests were routinely tested for HIV (based on the
      recommendation being made to all to test when having blood taken). Uptake was
      determined using the surrogate marker of ED attendees who had full blood counts
      (FBCs) as the denominator. Newly diagnosed patients were linked to care and
      contacts tested. Staff completed an anonymous online survey to determine
      acceptability at the end of the pilot study. RESULTS: A total of 2828 patients
      were tested over 3 months. Nineteen HIV-positive individuals were identified.
      Eight were newly diagnosed, of whom two were thought to be seroconverting. The
      prevalence of new diagnoses was 8/2828 (0.28%); for comparison, the Public Health
      England (PHE) actual prevalence for Tower Hamlets is 6.25/1000 (0.625%). Uptake
      for HIV testing was 30%, a significant increase from 72 tests performed in the 2
      months prior (P < 0.001). Ninety-five per cent of respondents to the staff survey
      agreed that routine HIV testing should be rolled out permanently in the ED.
      CONCLUSIONS: Despite an average uptake rate, there were 19 positive tests: eight
      in patients who were newly diagnosed, six in patients who had been lost to follow
      up, and five in patients who were known to be positive and linked to care. The
      staff survey indicated recognition of the importance of HIV testing in the ED.
      These persuasive data achieved short-term Clinical Commissioning Group (CCG)
      funding for routine ED testing.

PMID- 25604550
TI  - Global nucleosome positioning regulates salicylic acid mediated transcription in
      Arabidopsis thaliana.
AB  - BACKGROUND: The nucleosome positioning regulates the gene expression and many
      other DNA-related processes in eukaryotes. Genome-wide mapping of nucleosome
      positions and correlation of genome-wide nucleosomal remodeling with the changes
      in the gene expression can help us understanding gene regulation on genome level.
      RESULTS: In the present study, we correlate the gene expression and the genomic
      nucleosomal remodeling in response to salicylic acid (SA) treatment in A.
      thaliana. We have mapped genome-wide nucleosomes by performing tiling microarray
      using 146 bp mononucleosomal template DNA. The average nucleosomal coverage is
      approximately 346 bp per nucleosome both under the control and the SA-treated
      conditions. The nucleosomal coverage is more in the coding region than in the 5'
      regulatory regions. We observe approximately 50% nucleosomal remodeling on SA
      treatment where significant nucleosomal depletion and nucleosomal enrichment
      around the transcription start site (TSS) occur in SA induced genes and SA
      repressed genes respectively in response to SA treatment. Especially in the case
      of the SA-induced group, the nucleosomal remodeling over the minimal promoter in
      response to SA is especially significant in the Non-expresser of PR1 (NPR1)
      dependent genes. A detailed investigation of npr1-1 mutant confirms a distinct
      role of NPR1 in the nucleosome remodeling over the core promoter. We have also
      identified several motifs for various hormonal responses; including ABRE elements
      in the remodeled nucleosomal regions around the promoter region in the SA
      regulated genes. We have further identified that the W-box and TGACG/C motif,
      reported to play an important role in SA-mediated induction, are enriched in
      nucleosome free regions (NFRs) of the promoter region of the SA induced genes.
      CONCLUSIONS: This is the first study reporting genome-wide effects of SA
      treatment on the chromatin architecture of A. thaliana. It also reports
      significant role of NPR1 in genome-wide nucleosomal remodeling in response to SA.

PMID- 25604551
TI  - Stromal derived factor-1alpha in hippocampus radial glial cells in vitro
      regulates the migration of neural progenitor cells.
AB  - Stromal derived factor-1alpha (SDF-1alpha), a critical chemokine that promotes
      cell homing to target tissues, was presumed to be involved in the traumatic brain
      injury cortex. In this study, we determined the expression of SDF-1alpha in the
      hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA
      showed that mRNA transcription and SDF-1alpha proteins increased significantly
      after FF transection. In vitro, the expression of SDF-1alpha in radial glial
      cells (RGCs) incubated with deafferented hippocampus extracts was observed to be
      greater than in those incubated with normal hippocampus extracts. The co-culture
      of neural progenitor cells (NPCs) and RGCs indicated that the extracts of
      deafferented hippocampus induced more NPCs migrating toward RGCs than the normal
      extracts. Suppression or overexpression of SDF-1alpha in RGCs markedly either
      decreased or increased, respectively, the migration of NPCs. These results
      suggest that after FF transection, SDF-1alpha in the deafferented hippocampus was
      upregulated and might play an important role in RGC induction of NPC migration;
      therefore, SDF-1alpha is a target for additional research for determining new
      therapy for brain injuries. 

PMID- 25604555
TI  - Leveraging entrepreneurship as a means to improve the translation of outcomes
      research to healthcare improvement.

PMID- 25604556
TI  - Using a cardiac arrest registry to measure the quality of emergency medical
      service care: decade of findings from the Victorian Ambulance Cardiac Arrest
      Registry.
AB  - BACKGROUND: Although the value of clinical registries has been well recognized in
      developed countries, their use for measuring the quality of emergency medical
      service care remains relatively unknown. We report the methodology and findings
      of a statewide emergency medical service surveillance initiative, which is used
      to measure the quality of systems of care for patients with out-of-hospital
      cardiac arrest. METHODS AND RESULTS: Between July 1, 2002, and June 30, 2012,
      data for adult out-of-hospital cardiac arrest cases of presumed cardiac cause
      occurring in the Australian Southeastern state of Victoria were extracted from
      the Victorian Ambulance Cardiac Arrest Registry. Regional and temporal trends in
      bystander cardiopulmonary resuscitation, event survival, and survival to hospital
      discharge were analyzed using logistic regression and multilevel modeling. A
      total of 32,097 out-of-hospital cardiac arrest cases were identified, of whom
      14,083 (43.9%) received treatment by the emergency medical service. The risk
      adjusted odds of receiving bystander cardiopulmonary resuscitation (odds ratio
      [OR], 2.96; 95% confidence interval, 2.62-3.33), event survival (OR, 1.55; 95%
      confidence interval, 1.30-1.85), and survival to hospital discharge (OR, 2.81;
      95% confidence interval, 2.07-3.82) were significantly improved by 2011 to 2012
      compared with baseline. Significant variation in rates of bystander
      cardiopulmonary resuscitation and survival were observed across regions, with
      arrests in rural regions less likely to survive to hospital discharge. The median
      OR for interhospital variability in survival to hospital discharge outcome was
      70% (median OR, 1.70). CONCLUSIONS: Between 2002 and 2012, there have been
      significant improvements in bystander cardiopulmonary resuscitation and survival
      outcome for out-of-hospital cardiac arrest patients in Victoria, Australia.
      However, regional survival disparities and interhospital variability in outcomes
      pose significant challenges for future improvements in care.

PMID- 25604557
TI  - Trends in hypertension control among the older population of Spain from 2000 to
      2001 to 2008 to 2010: role of frequency and intensity of drug treatment.
AB  - BACKGROUND: The use of antihypertensive medication and hypertension control has
      significantly increased during recent decades in some developed countries, but
      the impact of improved drug treatment on blood pressure (BP) control in the
      population is unknown. METHODS AND RESULTS: Data were taken from 2 surveys
      representative of the population aged >= 60 years in Spain conducted with the
      same methodology in 2000 to 2001 and in 2008 to 2010. BP was measured 6*. The
      first BP reading was discarded, and the average of the remaining 3 to 5 BP
      readings was taken for analysis. Hypertension prevalence was 68.7% in 2000 to
      2001 and 66.0% in 2008 to 2010. Between both time periods there was an
      improvement in hypertension awareness (63.6%-67.7%), drug treatment among those
      aware (84.5%-87.5%), and BP control among treated hypertensives (30.3%-42.9%).
      Overall, BP control among all hypertensives increased from 16.3% to 25.4%. After
      adjustment for age, sex, education, hypertension duration, smoking, alcohol
      consumption, body mass index, sedentary behavior, diabetes mellitus,
      cardiovascular disease, and visits to the physician through logistic regression,
      ~ 7% of the improvement in BP control among all hypertensives was explained by
      higher hypertension awareness, and 36.2% was explained by a higher treatment
      rate. Among the treated hypertensives, 22.6% of the progress in BP control was
      because of the increase in the number of BP medications used in each patient.
      CONCLUSIONS: BP control among the older hypertensive population in Spain has
      improved from 2000 to 2001 to 2008 to 2010 because of a higher treatment rate and
      more intense antihypertensive drug treatment.

PMID- 25604558
TI  - Older patients with cardiac devices: the need for better patient-doctor
      conversations.

PMID- 25604560
TI  - Evaluation of the concentrations and distribution of carbonyl compounds in
      selected areas of a Brazilian bus terminal.
AB  - This study describes the determination of 30 carbonyl compounds (CCs) in three
      areas (bus boarding platform, passenger circulation area, and a pastry shop) of
      the Presidente Joao Goulart Bus Terminal, located at Niteroi City, RJ, Brazil,
      and in an open area 700 m distant from the terminal. Samples were collected using
      SEP-PAK cartridges impregnated with 2,4-dinitrophenylhydrazine, during May to
      July 2012. The hydrazones formed were analyzed using rapid resolution liquid
      chromatography with UV detection. The studied locations showed distinct profiles
      of distribution of CC. The circulation area, which is influenced by different
      pollution sources, presented an intermediate profile between that of the pastry
      shop and boarding platform. Formaldehyde and acetaldehyde were the most abundant
      CC, but acetaldehyde predominated in the pastry shop once it is a by-product of
      baking yeast fermentation. Samples taken in the pastry shop and circulation area
      showed significant concentrations of hexanaldehyde and nonanaldehyde emitted
      during cooking. The pastry shop showed the largest level of total CC among the
      studied areas followed by the circulation area, the boarding platform, and the
      open area.

PMID- 25604559
TI  - Building the case for novel clinical trials in pulmonary arterial hypertension.

PMID- 25604561
TI  - Photocatalytic degradation of pentachlorophenol by visible light Nu-F-TiO2 in the
      presence of oxalate ions: optimization, modeling, and scavenging studies.
AB  - The efficiency of heterogeneous photocatalysis using N-F-TiO2 as photocatalyst to
      degrade a priority pollutant, pentachlorophenol (PCP), in the presence of
      oxalates (OA) was investigated in detail. Response surface methodology was used
      to optimize the effect of three variables (catalyst concentration, OA/PCP ratio,
      and pH) on the photocatalytic degradation of pentachlorophenol. A quadratic model
      was established as a functional relationship between three independent variables
      and the degradation efficiency of PCP. The results of model fitting and
      statistical analysis demonstrated that the pH played a key role in the
      degradation of PCP. Within the studied experimental ranges, the optimum
      conditions for maximum PCP degradation efficiency (97.5 %) were: catalyst
      concentration 600 mg L(-1), OA/PCP ratio 2, and pH 10. The contribution of HO(.),
      O2 (.-), and e(-) produced during the photocatalytic treatment was investigated
      with the addition of scavengers. The photocatalytic degradation was essentially
      proceeded through an oxidative mechanism at both acid and alkaline pH values by
      HO(.) and O2 (.-) radicals attack. It was found that O2 (.-) were the major
      reactive species involved in PCP degradation in pH 4 and HO(.) in pH 10.

PMID- 25604562
TI  - Distributions and source apportionment of sediment-associated polycyclic aromatic
      hydrocarbons (PAHs) and hopanes in rivers and estuaries of Peninsular Malaysia.
AB  - In this study, the distributions and sources of sediment-associated polycyclic
      aromatic hydrocarbons (PAHs) and hopanes in the Malaysian rivers and estuaries
      were evaluated. The concentrations of 16 USEPA PAHs varied from 225.5 to 293.9
      (Perlis River), 195.2 to 481.2 (Kedah River), 791.2 to 1995.4 (Merbok River),
      231.2 to 426.7 (Perak River), and 3803.2 to 7442.7 ng g(-1) (Klang River) dry
      weight. PAHs can be classified as moderate in the Perlis, Kedah, and Perak
      Rivers, moderate to high in the Merbok River, and high to very high in the Klang
      River. The comparison of PAHs with sediment quality guidelines (SQGs) indicates
      that occasionally adverse biological effects may occur from total PAHs, low
      molecular weight (LMW), and high molecular weight (HMW) PAHs at stations 1, 2,
      and 3 of the Klang River and from total PAHs at station 2 of the Merbok River.
      The diagnostic ratios of individual PAHs indicate both petrogenic and pyrogenic
      origin PAHs with significant dominance of pyrogenic sources in the study areas.
      The results suggest that Malaysian sediments had hopane ratios (C29/C30) similar
      to MECO suggesting MECO as a major source of the petroleum hydrocarbons found in
      the sediments, which is consistent with results reported in previous studies.
      These findings demonstrate that effective and improved environmental regulations
      in Malaysia have shifted the source of petroleum hydrocarbons from petrogenic to
      pyrogenic origin.

PMID- 25604563
TI  - Use of EDTA in modified kinetic testing for contaminated drainage prediction from
      waste rocks: case of the Lac Tio mine.
AB  - The tools developed for acid mine drainage (AMD) prediction were proven
      unsuccessful to predict the geochemical behavior of mine waste rocks having a
      significant chemical sorption capacity, which delays the onset of contaminated
      neutral drainage (CND). The present work was performed in order to test a new
      approach of water quality prediction, by using a chelating agent solution (0.03 M
      EDTA, or ethylenediaminetetraacetic acid) in kinetic testing used for the
      prediction of the geochemical behavior of geologic material. The hypothesis
      underlying the proposed approach is that the EDTA solution should chelate the
      metals as soon as they are released by sulfide oxidation, inhibiting their
      sorption or secondary precipitation, and therefore reproduce a worst-case
      scenario where very low metal attenuation mechanisms are present in the drainage
      waters. Fresh and weathered waste rocks from the Lac Tio mine (Rio tinto, Iron
      and Titanium), which are known to generate Ni-CND at the field scale, were
      submitted to small-scale humidity cells in control tests (using deionized water)
      and using an EDTA solution. Results show that EDTA effectively prevents the
      metals to be sorbed or to precipitate as secondary minerals, therefore enabling
      to bypass the delay associated with metal sorption in the prediction of water
      quality from these materials. This work shows that the use of a chelating agent
      solution is a promising novel approach of water quality prediction and provides
      general guidelines to be used in further studies, which will help both
      practitioners and regulators to plan more efficient management and disposal
      strategies of mine wastes. 

PMID- 25604564
TI  - Oxidation of diclofenac with chlorine dioxide in aquatic environments: influences
      of different nitrogenous species.
AB  - The oxidation of diclofenac (DCF), a non-steroidal anti-inflammatory drug and
      emerging water pollutant, with chlorine dioxide was investigated under simulated
      water disinfection conditions. The reaction kinetics as functions of the initial
      concentrations of DCF, different nitrogenous species, and different pE values
      were experimentally determined. The results demonstrated that DCF reacted rapidly
      with ClO2, where more than 75 % of DCF (<=3.00 MUM) was removed by 18.94 MUM ClO2
      within 60 s. All of the reactions followed pseudo first-order kinetics with
      respect to DCF, and the rate constant, k obs, exhibited a significant decrease
      from 4.21 * 10(-2) to 8.09 * 10(-3) s(-1), as the initial DCF concentration was
      increased from 1.00 to 5.00 MUM. Furthermore, the degradation kinetics of DCF was
      clearly dependent on nitrogen-containing ion concentrations in the reaction
      solution. Ammonium and nitrite ions inhibited the DCF degradation by ClO2,
      whereas nitrate ion clearly initiated its promotion. In contrast, the inhibitory
      effect of NO2 (-) was more robust than that of NH4 (+). When the values of pE
      were gradually increased, the transformation of NH4 (+) to NO2 (-), and
      subsequently to NO3 (-), would occur, the rate constants were initially
      decreased, and then increased. When NH4 (+) and NO2 (-) coexisted, the inhibitory
      effect on the DCF degradation was less than the sum of the partial inhibitory
      effect. However, when NO2 (-) and NO3 (-) coexisted, the actual inhibition rate
      was greater than the theoretical estimate. These results indicated that the
      interaction of NH4 (+) and NO2 (-) was antagonistic, while the coexistence of NO2
      (-) and NO3 (-) was observed to have a synergistic effect in aqueous
      environments.

PMID- 25604565
TI  - Developmental toxic effects of monocrotophos, an organophosphorous pesticide, on
      zebrafish (Danio rerio) embryos.
AB  - The present study examined the response of zebrafish embryos exposed to different
      concentrations (10, 20, 30, 40, 50, and 60 mg/L) of monocrotophos under static
      conditions for 96 h. We found that mortality had occurred within 48 h at all test
      concentrations, later insignificant mortality was observed. Monocrotophos (MCP)
      can be rated as moderately toxic to the Zebrafish embryos with a 96-h median
      lethal concentration (LC50) of 37.44 +/- 3.32 mg/L. In contrast, it greatly
      affected the development of zebrafish embryos by inducing several developmental
      abnormalities like pericardial edema, altered heart development, spinal and
      vertebral anomalies in a concentration-dependent manner. A significant percent
      reduction in length by 9-48% and heart beats by 18-51% was observed in hatchlings
      exposed to LC10 and LC50 concentrations at 96 h when compared to controls. The
      process of looping formation of heart at embryonic stage was greatly affected by
      the LC50 concentration of MCP. The neurotoxic potentiality of MCP was assessed by
      using a marker enzyme, acetylcholinesterase in both in vitro and in vivo
      experiments. MCP was found to be the most potent inhibitor of AChE in vitro with
      an IC50 value of 4.3 * 10(-4) M. The whole-body AChE enzyme activity in vivo was
      significantly inhibited during the exposure tenure with the maximum inhibition of
      62% at 24 h.

PMID- 25604567
TI  - [Gap between the use of and need for youth care: research in Rotterdam
      neighbourhoods].
AB  - OBJECTIVE: To determine the relationship between the need for care and the use of
      care in the youth care system at neighbourhood level and the relationship with
      population characteristics, with consideration of the decentralisation of youth
      care. DESIGN: Descriptive, retrospective study. METHOD: Data on youth care use,
      indicators of need for care and population characteristics were gathered from
      monitors and the records of the municipality, institutions and health insurance
      companies. Data were grouped on a neighbourhood level (n = 49). For the analyses
      we used univariate and multivariate regression. We used these to distinguish
      between neighbourhoods with large and small gaps between youth care use and need
      for youth care. Differences between these neighbourhoods were analysed with t
      tests. RESULTS: A multivariate model showed that the percentage of youths with
      emotional problems and behavioural problems and the percentage of parents with
      self-reported need for care were not predictors of youth care use at a
      neighbourhood level. About two thirds of the variance in youth care use between
      neighbourhoods could be explained by the population characteristics of a
      neighbourhood, particularly the percentage of youths originally from non-western
      countries, the percentage of youths with a low level of education or special
      training and the percentage of people who received income support. The number of
      12-18-year-olds in a neighbourhood was a predictor of youth mental health care,
      and the percentage of youths in a single-parent family was a predictor of out
      patient youth and parenting support. Neighbourhoods with a large gap between the
      need for and use of youth care were socially more disadvantaged than
      neighbourhoods with a smaller gap. CONCLUSION: Population characteristics explain
      the rate of use of youth care better than the need for youth care in a
      neighbourhood as measured by municipal monitors. The possible gap between the use
      of and need for youth care on an individual level in neighbourhoods with many
      characteristics of disadvantage is an important focus point for future
      neighbourhood teams.

PMID- 25604566
TI  - Serum lipids in Brazilian children and adolescents: determining their reference
      intervals.
AB  - BACKGROUND: Demographic, geographic, environmental and genetic factors influence
      lipids. In many countries, the normal lipid ranges for laboratory tests are based
      on references from American children and adolescents. In this work, we determined
      the reference intervals (RIs) for total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-c), non-high-density lipoprotein cholesterol (nHDL
      c), low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) in
      Brazilian healthy children and adolescents. METHODS: A cross-sectional study was
      conducted of 1,866 randomly sampled healthy children and adolescents from
      kindergartens and schools. Blood samples were collected after a variable period
      of fasting based on the age of the participant. The upper cut-off points were the
      75(th) and 95(th) percentiles for TC, nHDL-c, LDL-c and TG. The 10(th) percentile
      (low) was used as the bottom level for HDL-c. Non-parametric tests were used for
      statistical analyses. RESULTS: The following RI and 75(th) and 95(th) percentiles
      were observed for each age interval. The 95(th) percentile values obtained for TC
      were: 1 to 2 years, 189 mg/dL, 3 to 8 years, 199 mg/dL; 9 to 12 years, 205 mg/dL.
      For the nHDL c, the only age group 1 to 12 years, this percentile value was 150
      mg/dL. For the LDL-cholesterol, the values corresponding to the percentiles
      above, aged 1 to 8 years and 9 to 12 years, were 132 mg/dL 139 mg/dL,
      respectively. For the triglycerides, the values corresponding to 95(th)
      percentile were: 1 year, 189 mg/dL; 2 to 5 years, 139 mg/dL; 6 to 12 years, 139
      mg/dL . The 10(th) percentiles for HDL-c were 24 mg/dL, 28 mg/dL, 32 mg/dL and 36
      mg/dL for children 1, 2, 3 and 4-12 years old, respectively. CONCLUSIONS: The
      lipid reference intervals defined in the studied Brazilian children and
      adolescents differ from those recommended by the international literature and
      should be used for clinical decisions contributing to improve the diagnosis in
      this particular group in our country.

PMID- 25604569
TI  - [Alcohol hallucinosis].
AB  - BACKGROUND: Alcohol hallucinosis is a rare complication of chronic alcohol abuse
      characterized by the acute onset of hallucinations during or after an episode of
      alcohol use. The hallucinations may persist for a long time, due to which the
      clinical picture can be mistaken for a disorder on the schizophrenia spectrum.
      The prognosis tends to be favourable, although untreated cases are associated
      with a considerable mortality risk (37% in eight years). CASE DESCRIPTION: A 38
      year-old male was admitted to a psychiatric hospital with hallucinations of acute
      onset during alcohol abuse which persisted for two months of abstinence. The
      patient experienced visual, auditory and tactile hallucinations during which time
      his consciousness, attention, orientation and higher cognitive functions remained
      intact. Somatic and neuroimaging investigations showed no abnormalities. The
      patient partially recovered on treatment with haloperidol. CONCLUSION: If
      hallucinations are experienced during or after a period of alcohol abuse, the
      diagnosis of alcohol hallucinosis should be considered. The diagnosis must be
      distinguished from delirium tremens and schizophrenia spectrum disorder as
      treatment and prognosis are essentially different.

PMID- 25604570
TI  - [A man with thumb nail abnormalities].
AB  - A 56-year-old, otherwise healthy patient was seen in the Dermatology department
      with longstanding central splitting of the nail plate of his right thumb. Because
      his left thumb nail also started to become affected he sought help. DIAGNOSIS:
      median canaliform nail dystrophy.

PMID- 25604571
TI  - Pathophysiology and management of hepatic encephalopathy 2014 update: Ammonia
      toxicity and hyponatremia.
AB  - Hyperammonemia is a major factor involved in the pathogenesis of hepatic
      encephalopathy (HE). Ammonia elicits astrocyte swelling and causes brain edema.
      In addition, hyponatremia, a condition frequently observed in hepatic cirrhosis,
      also exacerbates brain edema, potentially becoming a factor that exacerbates HE.
      Therefore, as a treatment strategy for HE, alleviating ammonia toxicity is
      essential. In addition to restricting protein intake, synthetic disaccharides
      such as lactulose and lactitol, probiotics that improve gut flora, and rifaximin,
      an antibiotic with poor bioavailability, are also administrated. Additionally,
      branched-chain amino acids and carnitine have also been administrated. Moreover,
      we investigated the current trend in the concomitant use of drugs with different
      mechanisms of action. In Japan, the V2 receptor antagonist tolvaptan can be
      administrated to hepatic cirrhosis patients with fluid retention. This drug is
      also useful as a countermeasure for hyponatremia in hepatic cirrhosis, and
      elucidating its effects in HE patients may therefore become an agenda in the
      future. These observations indicate that ammonia toxicity, gut flora control and
      low sodium control are major focuses in HE improvement and long-term prognosis. 

PMID- 25604572
TI  - Sleep disturbance and chronic widespread pain.
AB  - Musculoskeletal pain is common and often occurs at multiple sites. Persons with
      chronic widespread pain (CWP) often report disturbed sleep. Until recently, the
      relationship between sleep disturbance and CWP has been unclear: does poor sleep
      increase the risk of developing CWP, do people with CWP develop poor sleep as a
      consequence of their pain, or is the relationship bi-directional? In this
      article, we have focused on the relationship between insomnia and CWP. We briefly
      present descriptive epidemiological data for insomnia and CWP. We then summarise
      the available evidence which supports the hypothesis that the relationship is bi
      directional. Finally, we discuss the clinical management of CWP and insomnia in
      primary care, where the vast majority of cases of CWP are managed. 

PMID- 25604573
TI  - Emerging roles of innate immune signaling and toll-like receptors in fibrosis and
      systemic sclerosis.
AB  - Pathological fibrosis is a distinguishing hallmark of systemic sclerosis (SSc) as
      well as a number of more common conditions. Fibrosis is a complex and dynamic
      process associated with immune dysregulation, vasculopathy, and uncontrolled
      extracellular matrix production leading to intractable scar formation in the skin
      and internal organs. Persistent or recurrent chemical, infectious, mechanical, or
      autoimmune injury in genetically predisposed individuals causes sustained
      fibroblasts activation. Innate immune signaling via toll-like receptors (TLRs) is
      increasingly recognized as a key player driving the persistent fibrotic response
      in SSc. In particular, expression of TLR4 as well as its endogenous ligands are
      elevated in lesional tissue from patients with SSc. Ligand-induced TLR4
      activation elicits potent stimulatory effects on fibrotic gene expression and
      myofibroblast differentiation. Furthermore, TLR4 appears to sensitize fibroblasts
      to the profibrotic stimulatory effect of transforming growth factor-beta. This
      review highlights recent advances and emerging paradigms for understanding the
      regulation, complex functional roles, and therapeutic potential of TLRs in SSc
      pathogenesis. 

PMID- 25604574
TI  - Pulmonary hypertension in antiphospholipid syndrome.
AB  - Pulmonary hypertension (PH) is a rare but life-threatening condition in
      antiphospholipid syndrome (APS) patients with or without systemic lupus
      erythematosus (SLE). The definition of PH is based on hemodynamic parameters
      estimated by transthoracic echocardiography (TTE) and confirmed by right heart
      catheterization (RHC). New evidence suggests that antiphospholipid antibodies
      (aPL) in SLE patients increase the risk of PH; however, studies yield conflicting
      results. Hypotheses regarding the impact of aPL on PH include large vessel and
      microvascular thrombosis, and endothelial remodeling. Natural history of PH is
      progressive worsening mainly due to recurrent pulmonary embolism. The management
      in APS patients includes anticoagulation; patients undergoing pulmonary
      endarterectomy need to be closely monitored because of an increased risk of
      thrombotic complications. 

PMID- 25604575
TI  - Catastrophic APS in the context of other thrombotic microangiopathies.
AB  - The catastrophic antiphospholipid syndrome (CAPS) is a rare disease that affects
      1 % of cases with antiphospholipid syndrome (APS). CAPS can mimic or overlap with
      different thrombotic diseases; many patients present with a microthrombotic storm
      or thrombotic microangiopathic hemolytic anemia (TMHA). Thus, the differential
      diagnosis of CAPS includes thrombotic thrombocytopenic purpura (TTP), typical and
      atypical hemolytic uremic syndrome (HUS), systemic infections, malignancies,
      pregnancy-related disorders, malignant hypertension, heparin-induced
      thrombocytopenia, and drug-induced thrombotic microangiopathies. Antiphospholipid
      antibody (aPL) positivity has been proposed as the clue in this differential
      diagnosis; however, aPL can also occur in healthy people and in those with
      infections or malignancies. Thus, the differential diagnosis of an aPL-positive
      patient presenting with a microthrombotic storm is broad; the workup should
      include a special attention to signs of infection and disseminated malignant
      disease, assessing the funduscopic signs of malignant hypertension, testing
      ADAMTS13 activity and anti-heparin-platelet factor 4 (HPF4) antibodies, and
      searching previous exposure to certain drugs. This article aims to review the
      main diseases included in the differential diagnosis of CAPS in the context of
      other thrombotic microangiopathies. 

PMID- 25604576
TI  - Clinical observation of the time course of raised intracranial pressure after
      subarachnoid hemorrhage.
AB  - The time course of intracranial pressure (ICP) after subarachnoid hemorrhage
      (SAH) is not well known. This retrospective study was conducted to investigate
      the occurrence and the dynamic variation of raised ICP post-SAH. ICP was
      prospectively studied in 120 patients with SAH who were admitted to neurocritical
      care within 24 h of hemorrhage. Patients underwent continuous ICP monitoring for
      at least 7 days, unless they died. Clinical status on admission, radiographic
      tests, treatment details and neurological outcome on discharge were analyzed in
      relation to ICP. The highest daily mean ICP and the day when ICP reduced to
      normal levels were assessed. Of the 120 patients studied, 112 (93.3 %)
      encountered ICP elevation whilst in hospital. The daily mean ICP was higher in
      Hunt and Hess grades IV-V patients than grades I-III patients (P = 0.01). The
      elevated ICP remained at a higher level for the initial 3 days (grades I-III
      patients) or 4 days (grades IV-V patients), after which the pressure decreased
      towards normal levels. The in-patient mortality was significantly increased in
      the high ICP variability group (P = 0.001), which was divided by the cutoff point
      using receiver operating characteristic curve analysis. Raised ICP mainly occurs
      within 8 days post-SAH, especially the initial 3-4 days. Those highlight the need
      for earlier management of ICP after SAH.

PMID- 25604577
TI  - Reading beyond the glance: eye tracking in neurosciences.
AB  - From an interdisciplinary approach, the neurosciences (NSs) represent the
      junction of many fields (biology, chemistry, medicine, computer science, and
      psychology) and aim to explore the structural and functional aspects of the
      nervous system. Among modern neurophysiological methods that "measure" different
      processes of the human brain to salience stimuli, a special place belongs to eye
      tracking (ET). By detecting eye position, gaze direction, sequence of eye
      movement and visual adaptation during cognitive activities, ET is an effective
      tool for experimental psychology and neurological research. It provides a
      quantitative and qualitative analysis of the gaze, which is very useful in
      understanding choice behavior and perceptual decision making. In the high tech
      era, ET has several applications related to the interaction between humans and
      computers. Herein, ET is used to evaluate the spatial orienting of attention, the
      performance in visual tasks, the reactions to information on websites, the
      customer response to advertising, and the emotional and cognitive impact of
      various spurs to the brain. 

PMID- 25604578
TI  - Supramolecular chemical shift reagents inducing conformational transitions: NMR
      analysis of carbohydrate homooligomer mixtures.
AB  - We introduce the concept of supramolecular chemical shift reagents as a tool to
      improve signal resolution for the NMR analysis of homooligomers. Non-covalent
      interactions with the shift reagent can constrain otherwise flexible analytes
      inducing a conformational transition that results in signal separation. Here we
      use this approach for the quantitative analysis of a complex homooligomeric
      glycan mixture. 

PMID- 25604579
TI  - Intrinsic topological insulator Bi(1.5)Sb(0.5)Te(3-x)Se(x) thin crystals.
AB  - The quaternary topological insulator (Bi,Sb)2(Te,Se)3 has demonstrated
      topological surface states with an insulating bulk. Scientists have identified an
      optimized composition of Bi(1.5)Sb(0.5)Te(1.7)Se(1.3) with the highest
      resistivity reported. But the physics that drive to this composition remains
      unclear. Here we report the crystal structure and the magneto-transport
      properties of Bi(1.5)Sb(0.5)Te(3-x)Se(x) (BSTS) series. A correlation between the
      structure and the physical properties has been revealed. We found out that within
      the rhombohedral structure, the composition with most Te substituting Se has the
      highest resistivity. On the other hand, segregation of other composition phases
      will introduce much higher bulk concentration.

PMID- 25604580
TI  - Ultra high performance liquid chromatography with synapt high-definition mass
      spectrometry and a pattern recognition approach to characterize chemical
      constituents and rat metabolites after the oral administration of Phellinus
      igniarius.
AB  - Phellinus igniarius has antibacterial, antiviral, antioxidative, antitumor, and
      antimutagenic effects. In this study, an integrative pattern recognition approach
      using principal component analysis and orthogonal partial least squares
      discriminant analysis was successfully applied for the rapid analysis of natural
      compounds in traditional Chinese medicine. An ultra high performance liquid
      chromatography with synapt high-definition mass spectrometry method and MassLynx
      software was used. This method employed gradient elution to rapidly analyze and
      characterize chemical constituents and metabolites after the oral administration
      of a P. igniarius ethanol extract. There were 24 peaks within 10 min of the
      analysis time and 20 of these were identified or tentatively characterized on the
      basis of their fragmentation behaviors. In the S-plot of the orthogonal partial
      least squares discriminant analysis, 27 ions were extracted to make the serum.
      Among them, nine absorbed the prototype components and 18 metabolites were
      identified in vivo. Glucuronidation, oxidation, and methylation were the major
      metabolic reactions. This study is the first systematic analysis and
      characterization of the chemical constituents and metabolites in an ethanol
      extract of P. igniarius. This method can be applied to the rapid analysis and
      characterization of constituents in rat serum after the oral administration of
      other compounds used in traditional Chinese medicines. 

PMID- 25604581
TI  - Malpighian tubules are important determinants of Pseudomonas transstadial
      transmission and longtime persistence in Anopheles stephensi.
AB  - BACKGROUND: Pseudomonas is a genus of bacteria commonly found in investigations
      of gut microbes in malaria mosquitoes. Among those mosquitoes is the dominating
      malaria vector in Asia, Anopheles stephensi, where Pseudomonas is a prevailing
      bacterium and natural inhabitant of its breeding places. In order to explore the
      reason for finding Pseudomonas so frequently, an investigation of its
      localization and transstadial properties was undertaken. METHODS: A Pseudomonas
      isolate from An. stephensi was transformed successfully with an endogenous
      plasmid modified to express green fluorescent protein (GFP). Subsequently, the
      Pseudomonas-GFP was added to the laboratory larval breeding place of An.
      stephensi and taken up by the larvae. After 24 hours, the larvae were cleaned and
      moved to a bath with double-distilled water. Also, female adults were fed sugar
      solution containing Pseudomonas-GFP. The Pseudomonas-GFP was traced in the
      alimentary canal of larvae, pupae and adults. RESULTS: Fluorescent microscopy and
      PCR assays showed that the Pseudomonas bacteria underwent transstadial
      transmission from larvae to pupae and then to adults. In blood-fed female
      mosquitoes, the bacteria increased in numbers and remained in the mosquito body
      for at least three weeks after eclosion. In addition to the midgut, the
      Malpighian tubules of both larvae and adult mosquitoes were colonized by the
      bacteria. Also Pseudomonas-GFP that was distributed through sugar solution was
      able to colonize the Malpighian tubules of adult females. CONCLUSIONS:
      Colonization of the Malpighian tubules by Pseudomonas bacteria seems to be
      important for the transstadial passage from larvae to adult and presumably for
      the longevity of the bacteria in the adult mosquito. The existence of an entry
      point in the larval stage, and the long duration in the female gut, opens up for
      a possible use of Pseudomonas in mosquito paratransgenesis.

PMID- 25604582
TI  - Association between co-inhibitory molecule gene tagging single nucleotide
      polymorphisms and the risk of colorectal cancer in Chinese.
AB  - PURPOSE: T lymphocyte immune responses are controlled by both co-stimulatory and
      co-inhibitory signaling through T cell co-receptors. Cytotoxic T lymphocyte
      antigen-4 (CTLA-4), programmed death 1 (PD-1) and B and T lymphocyte attenuator
      (BTLA) are all co-inhibitory molecules that negatively regulate the activation of
      T cells. In this study, we investigated the relationship between ten tagging SNPs
      in three co-inhibitory molecule genes and colorectal cancer (CRC). METHODS: We
      conducted a hospital-based case-control study consisting of 601 cases with CRC
      and 627 CRC-free individuals from the Heilongjiang Province of China. RESULTS:
      The rs7421861 CT genotype was significantly associated with the risk of
      colorectal cancer compared to the wild-type TT genotype (adjusted OR 1.314, 95%
      CI 1.012-1.706, P = 0.041). The rs2705535 TT genotype was associated with the
      risk of rectal cancer [OR 1.819 (1.093-3.027), P = 0.021]. There was statistical
      interaction between the PD-1/rs2227982 (CT + TT) genotypes and high seafood
      intake (>once/week), as well as the CTLA-4/rs231777 variant and high pungent food
      intake (>3 times/week). The AG + AA genotypes of CTLA-4/rs3087243 statistically
      and antagonistically interacted with soybeans, pork and alcohol intake and were
      associated with CRC risk. Analogously, BTLA/rs1844089 interacted with pork
      intake, PD-1/rs7421861 with beef and lamb consumption and PD-1/rs6710479 with
      barbecue consumption. Haplotype G-C-G-A-T-T-A was significantly associated with
      CRC risk (OR 1.221 P = 0.034). CONCLUSIONS: These data indicate potential
      associations between BTLA and PD-1 polymorphisms and CRC susceptibility.
      Additionally, the three co-inhibitory molecule gene SNPs have environmental
      interactions associated with CRC risk.

PMID- 25604583
TI  - Dietary heterocyclic amine intake, NAT2 genetic polymorphism, and colorectal
      adenoma risk: the colorectal adenoma study in Tokyo.
AB  - BACKGROUND: While several studies have provided support for a positive
      association between meat intake and colorectal neoplasia, the role of
      heterocyclic amines (HCA), which is hypothesized to underline this relation, has
      been less consistent. We evaluated the association of HCA intake with colorectal
      adenoma risk in a case-control study in a middle-aged Japanese population.
      METHODS: Study subjects were 738 patients with adenoma and 697 controls who
      underwent total colonoscopy between 2004 and 2005 and responded to self
      administered lifestyle and dietary questionnaires. HCA exposure concentration was
      estimated from meat and fish intake based on an HCA database that was validated
      against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values measured in
      human hair. Logistic regression models were used to estimate ORs and 95%
      confidence interval (CI) for the association between HCA and colorectal adenoma
      risk after adjusting for potential confounders. RESULTS: High intake of 2-amino
      3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and total HCA was associated with an
      increased risk of colorectal adenoma in women but not in men. The multivariate
      adjusted OR for the highest versus lowest quartile in women was 2.10 (95% CI,
      1.20-3.67; Ptrend = 0.01) for MeIQ and 1.73 (95% CI, 0.99-3.01; Ptrend = 0.03)
      for total HCA. No clear association with PhIP or 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) estimates and no effect modification by NAT2 acetylation
      genotype was observed. CONCLUSIONS: This study suggests that high MeIQ and total
      HCA estimates are positively associated with colorectal adenoma risk. IMPACT: The
      findings add to evidence that HCA may play a role in colorectal carcinogenesis in
      humans. Cancer Epidemiol Biomarkers Prev; 24(3); 613-20. (c)2015 AACR.

PMID- 25604584
TI  - The Experience of Military Families with Children with Autism Spectrum Disorders
      During Relocation and Separation.
AB  - Military families with a child with autism spectrum disorder (ASD) are
      underrepresented in the literature. In order to provide appropriate services,
      research must be done to determine the needs of these families. A qualitative
      methodology was used to interview military spouses with children with ASD about
      their experiences with therapeutic services. Overall, results indicate military
      families with a child with ASD experience challenges associated with both the
      military lifestyle and having a child with special needs. Due to their membership
      in two groups prone to support limitations and therapeutic service accessibility
      issues, military families with a child with ASD may be at additional risk for
      high levels of stress and difficulty obtaining and maintaining ASD related
      services. 

PMID- 25604585
TI  - Brief Report: Coherent Motion Processing in Autism: Is Dot Lifetime an Important
      Parameter?
AB  - Contrasting reports of reduced and intact sensitivity to coherent motion in
      autistic individuals may be attributable to stimulus parameters. Here, we
      investigated whether dot lifetime contributes to elevated thresholds in children
      with autism. We presented a standard motion coherence task to 31 children with
      autism and 31 typical children, with both limited and unlimited lifetime
      conditions. Overall, children had higher thresholds in the limited lifetime
      condition than in the unlimited lifetime condition. However, children with autism
      were affected by this manipulation to the same extent as typical children and
      were equally sensitive to coherent motion. Our results suggest that dot lifetime
      is not a critical stimulus parameter and speak against pervasive difficulties in
      coherent motion perception in children with autism. 

PMID- 25604586
TI  - Renal function during long-term lithium treatment: a cross-sectional and
      longitudinal study.
AB  - BACKGROUND: The effects of lithium treatment on renal function have been
      previously shown, albeit with discrepancies regarding their relevance. In this
      study, we examined glomerular filtration rate in patients treated with lithium
      for up to 33 years. METHODS: All lithium patients registered from 1980 to 2012 at
      a Lithium Clinic were screened. Estimated glomerular filtration rate (eGFR) was
      calculated from serum creatinine concentration using the Modification of Diet in
      Renal Disease Study Group equation. A cross-sectional evaluation of the last
      available eGFR of 953 patients was carried out using multivariate regression
      analysis for gender, current age, and duration of lithium treatment. Survival
      analysis was subsequently applied to calculate the time on lithium needed to
      enter the eGFR ranges 45 to 59 mL/min/1.73 m2 (G3a) or 30 to 44 mL/min/1.73 m2
      (G3b). Finally, 4-year follow-up of eGFR was examined in subgroups of patients
      who, after reduction to an eGFR lower than 45 mL/min/1.73 m2 either i) continued
      lithium at the same therapeutic range or ii) discontinued lithium or continued at
      concentrations below the therapeutic range (0.5 mmol/L). RESULTS: In the cross
      sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73
      m2), in older patients (0.73 mL/min/1.73 m2 per year of age), and in patients
      with longer lithium treatment (0.73 mL/min/1.73 m2 per year). Half of the
      patients treated for longer than 20 years had an eGFR lower than 60 mL/min/1.73
      m2. The median time on lithium taken to enter G3a or G3b was 25 years (95% CI,
      23.2-26.9) and 31 years (95% CI, 26.6-35.4), respectively. Progression of renal
      failure throughout the 4-year follow-up after a reduction to an eGFR lower than
      45 mL/min/1.73 m2 did not differ between the subgroup who continued lithium as
      before and the subgroup who either discontinued lithium or continued at
      concentrations below the therapeutic range. CONCLUSIONS: Duration of lithium
      treatment is to be added to advancing age as a risk factor for reduced glomerular
      filtration rate. However, renal dysfunction tends to appear after decades of
      treatment and to progress slowly and irrespective of lithium continuation.

PMID- 25604587
TI  - Ten years of transcriptomics in wild populations: what have we learned about
      their ecology and evolution?
AB  - Molecular ecology has moved beyond the use of a relatively small number of
      markers, often noncoding, and it is now possible to use whole-genome measures of
      gene expression with microarrays and RNAseq (i.e. transcriptomics) to capture
      molecular response to environmental challenges. While transcriptome studies are
      shedding light on the mechanistic basis of traits as complex as personality or
      physiological response to catastrophic events, these approaches are still
      challenging because of the required technical expertise, difficulties with
      analysis and cost. Still, we found that in the last 10 years, 575 studies used
      microarrays or RNAseq in ecology. These studies broadly address three questions
      that reflect the progression of the field: (i) How much variation in gene
      expression is there and how is it structured? (ii) How do environmental stimuli
      affect gene expression? (iii) How does gene expression affect phenotype? We
      discuss technical aspects of RNAseq and microarray technology, and a framework
      that leverages the advantages of both. Further, we highlight future directions of
      research, particularly related to moving beyond correlation and the development
      of additional annotation resources. Measuring gene expression across an array of
      taxa in ecological settings promises to enrich our understanding of ecology and
      genome function. 

PMID- 25604588
TI  - The use of "2-octyl cyanoacrylate" as skin adhesive in pediatric and congenital
      cardiac surgery.
AB  - AIM: The aim of this paper was to evaluate the safety and cost-effectiveness of
      "2-octyl-cyanoacrylate" as skin adhesive in congenital heart surgery. METHODS:
      From April 2010 to December 2011, we collected data from 300 patients who
      underwent cardiac surgery for congenital heart disease. We divided our population
      into 3 groups: group-1 (N.=100):"2-octyl-cyanoacrylate" has been used to replace
      the intra-dermal suture line; group-2 (N.=100):"2-octyl-cyanoacrylate" has been
      utilized as a barrier ("add-on measure") in addition to the intra-dermal suture
      line, group-3 (N.=100) with a standard intra-dermal suture line. RESULTS: Median
      age of patients was 1.36 years. One-hundred and thirty-nine patients were younger
      than 12 months and 56 older than 16 years. There were 11 wound dehiscence (3.6%)
      (2 in group-1 and 9 in group-3, P=0.001) and 1 superficial wound infection (group
      1). Six patients (2%) required surgical wound revision (2 in group-1 and 4 in
      group-3, P=NS). Wound complication was significantly associated to delayed
      sternal closure (3/12 patients, 25% versus 13/288 patients, 4.5%) (P=0.04).
      Median cost (intra-/postoperative) for wound treatment was lower in group-1 and 2
      (19+/-5.5 and 23.9+/-7.4 ? respectively) when compared to Group-3 (26.7+/-3.2)
      (P<0.0001). CONCLUSION: The use of "2-octyl-cyanoacrylate" proved to be safe and
      effective; the "add-on measure" strategy provided the best cost-effective
      solution.

PMID- 25604589
TI  - Vitamin D status and type 1 diabetes in children: evaluation according to
      latitude and skin color.
AB  - AIM: We aim to investigate vitamin D (25OHD) levels in children with or without
      type 1 diabetes (T1D) according to latitude and skin color. METHODS: We compared
      25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan
      origin, with healthy control subjects matched for age and ethnicity. Data of
      resident children in Morocco, with and without T1D, were used for comparison.
      RESULTS: Caucasian (21.4+/-1.5 vs. 24.0+/-0.5 ng/mL, P<0.05) and Moroccan
      children with T1D (12.0+/-2.6 vs. 17.1+/-1.7 ng/mL, P<0.05) living in Piedmont
      had lower 25OHD levels than their counterparts without diabetes. Moroccan
      children living in Morocco with and without T1D had similar 25OHD levels. Vitamin
      D deficiency was associated with T1D in Caucasian and Moroccan children living in
      Piedmont (OR: 1.720, CI95% 1.034-2.860, P<0.03), CONCLUSION: Lower vitamin D
      levels were associated with T1D in Piedmont. Further studies are necessary to
      explain a possible relationship between vitamin D and T1D.

PMID- 25604590
TI  - Hyperexcitability as the main sign of neonatal hypoxia.

PMID- 25604591
TI  - Initial resuscitation and management of pediatric septic shock.
AB  - The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and
      health care utilization costs worldwide. The initial resuscitation and management
      of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue
      perfusion and restoration of adequate cardiovascular function; 2) eradication of
      the inciting invasive infection, including prompt administration of empiric broad
      spectrum antimicrobial medications; and 3) supportive care of organ system
      dysfunction. Efforts to improve early and aggressive initial resuscitation and
      ongoing management strategies have improved outcomes in pediatric severe sepsis
      and septic shock, though many questions still remain as to the optimal
      therapeutic strategies for many patients. In this article, we will briefly review
      the definitions, epidemiology, clinical manifestations, and pathophysiology of
      sepsis and provide an extensive overview of both current and novel therapeutic
      strategies used to resuscitate and manage pediatric patients with severe sepsis
      and septic shock. 

PMID- 25604593
TI  - Prevalence of off-label use of oral oncolytics at a community cancer center.
AB  - PURPOSE: Oral oncolytics are becoming increasingly utilized for cancer treatment,
      but the frequency of off-label oral oncolytic use is not well described. The
      extent of off-label oral oncolytic use is a concern because the clinical benefits
      of such use to patients may not outweigh adverse health outcomes or cost
      concerns. METHODS: Prescription data for January 2011 through November 2013 from
      the St. Lukes Mountain States Tumor Institute (MSTI) Oral Chemotherapy program
      (OCP) was retrospectively analyzed. Use was classified as "on-label" if the
      cancer site, stage, and line of therapy met the FDA-approved indication. All
      other uses were classified as "off- label." Off-label use was further evaluated
      by whether it conformed to and was supported by National Comprehensive Cancer
      Network (NCCN) guideline recommendations. RESULTS: Twelve hundred and six first
      fill oral chemotherapy prescriptions were reviewed, representing 990 unique
      patients and 44 individual medications. On-label use amounted to 71% and off
      label use amounted to 29%. Eighty-eight percent of off-label uses were supported
      by NCCN guideline recommendations. A total of 3.3% of all prescriptions analyzed
      were for off-label uses not supported by NCCN guideline recommendations. The top
      five oral chemotherapies prescribed for off-label uses were capecitabine,
      temozolomide, lenalidomide, abiraterone, and everolimus. CONCLUSION: Oral
      chemotherapies are more often used on label than off label in current practice at
      our community cancer center. The majority of off-label use of oral oncolytics in
      this study was supported by NCCN guideline recommendations.

PMID- 25604592
TI  - Pulmonary arterial hypertension associated with congenital heart disease and
      Eisenmenger syndrome: current practice in pediatrics.
AB  - Pulmonary arterial hypertension (PAH) is an uncommon but serious disease
      characterized by severe pulmonary vascular disease and significant morbidity and
      mortality. PAH associated with congenital heart disease (APAH-CHD) is one
      etiology of PAH that has innate characteristics delineating it from other forms
      of PAH. The patient with APAH-CHD presents with unique challenges consisting of
      not only pulmonary vascular disease but also the complexity of the cardiac
      lesion. Eisenmenger syndrome (ES) represents the severe end of the spectrum for
      disease in APAH-CHD. Over time, systemic-to-pulmonary shunting through cardiac
      defects increases pulmonary vascular resistance to levels significant enough to
      reverse shunting across the defect. Historically, ES patients have been reported
      to have better outcomes than IPAH despite similarities in pulmonary vascular
      disease. However, recent studies are challenging this notion. Nonetheless, APAH
      CHD survival has improved with the advent of modern PAH targeted therapies. New
      therapeutic options have allowed us to reconsider the dogma of inoperability in
      APAH-CHD patients with unrepaired defects. Certainly advances have been made,
      however, investigators must continue to advance the field through controlled
      clinical trials in both adult and pediatric APAH-CHD patients. 

PMID- 25604595
TI  - Escalation of oncologic services at the end of life among patients with
      gynecologic cancer at an urban, public hospital.
AB  - PURPOSE: Use of oncology-related services is increasingly scrutinized, yet
      precisely which services are actually rendered to patients, particularly at the
      end of life, is unknown. This study characterizes the end-of-life use of medical
      services by patients with gynecologic cancer at a safety-net hospital. METHODS:
      Oncologic history and metrics of medical use (eg, hospitalizations, chemotherapy
      infusions, procedures) for patients with gynecologic oncology who died between
      December 2006 and February 2012 were evaluated. Mixed-effect regression models
      were used to test time effects and construct usage summaries. RESULTS: Among 116
      subjects, cervical cancer accounted for the most deaths (42%). The median age at
      diagnosis was 55 years; 63% were Hispanic, and 65% had advanced disease. Only 34%
      died in hospice care. The median times from do not resuscitate/do not intubate
      documentation and from last therapeutic intervention to death were 9 days and 55
      days, respectively. Significant time effects for all services (eg,
      hospitalizations, diagnostics, procedures, treatments, clinic appointments) were
      detected during the patient's final year (P < .001), with the most dramatic
      changes occurring during the last 2 months. Patients with longer duration of
      continuity of care used significantly fewer resources toward the end of life.
      CONCLUSION: To our knowledge, this is the first report enumerating medical
      services obtained by patients with gynecologic cancer in a large, public hospital
      during the end of life. Marked changes in interventions in the patient's final 2
      months highlight the need for cost-effective, evidence-based metrics for
      delivering cancer care. Our data emphasize continuity of care as a significant
      determinant of oncologic resource use during this critical period.

PMID- 25604594
TI  - Trends in use and safety of image-guided transthoracic needle biopsies in
      patients with cancer.
AB  - PURPOSE: Image-guided transthoracic needle biopsy (IGTTNB) is an important tool
      in the diagnosis of patients with cancer. Common complications include
      pneumothorax and chest tube placement, with rates ranging from 6% to 57%. We
      performed a population-based study to determine patterns of use, complications,
      and costs associated with IGTTNB. METHODS: The Premier Perspective database was
      used to identify patients with cancer with >= one claim for IGTTNB from 2006 to
      2012. Patients were stratified on the basis of inpatient versus outpatient
      setting. Pneumothorax was defined by a new claim within 1 month of IGTTNB;
      hospitalization and chest tube placement rates were analyzed. Multivariable
      analysis was used to identify factors associated with pneumothorax. RESULTS: We
      Identified 79,518 patients with cancer who underwent IGTTNB: 42,955 (54.0%)
      outpatients and 36,563 (46.0%) inpatients. Of patients who underwent outpatient
      IGTTNB, 5,261 (12.2%) developed a pneumothorax. Of those, 1,006 (19.1%, 2.3% of
      total) were hospitalized, and 180 (3.4%, 0.42% of total) required chest tubes.
      Pneumothorax after outpatient IGTTNB was associated with number of comorbidities,
      rural site, hospital bed size of more than 600, and biopsy of parenchymal as
      opposed to pleural lesions. Of patients who underwent inpatient IGTTNB, 7,830
      (21.4%) developed a pneumothorax, and 2,894 (36.0%, 7.9% of total) required chest
      tube. Over time, total IGTTNB volume increased by 40.6%, and mean outpatient cost
      per procedure increased by 24.4%. CONCLUSION: While pneumothorax was frequent in
      outpatients, rates of hospitalization and chest tube placement were low. As
      screening for lung cancer increases, we anticipate an increased need for IGTNBB.
      Patients can be reassured by the low rate of serious complications.

PMID- 25604596
TI  - Why bundled payments could drive innovation: an example from interventional
      oncology.
AB  - Some have suggested that the current fee-for-service health care payment system
      in the United States stifles innovation. However, there are few published
      examples supporting this concept. We implemented an innovative temporary balloon
      occlusion technique for yttrium 90 radioembolization of nonresectable liver
      cancer. Although our balloon occlusion technique was associated with similar
      patient outcomes, lower cost, and faster procedure times compared with the
      standard-of-care coil embolization technique, our technique failed to gain
      widespread acceptance. Financial analysis revealed that because the balloon
      occlusion technique avoided a procedural step associated with a lucrative Current
      Procedural Terminology billing code, this new technique resulted in a significant
      decrease in hospital and physician revenue in the current fee-for-service payment
      system, even though the new technique would provide a revenue enhancement through
      cost savings in a bundled payment system. Our analysis illustrates how in a fee
      for-service payment system, financial disincentives can stifle innovation and
      advancement of health care delivery. 

PMID- 25604597
TI  - Population-based assessment of emergency room visits and hospitalizations among
      women receiving adjuvant chemotherapy for early breast cancer.
AB  - PURPOSE: Adjuvant chemotherapy is considered standard care for patients with
      lymph node (LN) -positive and high-risk LN-negative early breast cancer (EBC).
      Although chemotherapy-associated toxicities are documented in clinical trials,
      the impact of toxicities on emergency room (ER) visits and hospitalizations (ER +
      Hs) at a population level with contemporary chemotherapy is unknown. We undertook
      a population-based study of ER + Hs in patients with EBC receiving adjuvant
      chemotherapy compared with noncancer controls (NCCs). METHODS: All patients
      diagnosed with EBC between January 2007 and December 2009 in Ontario, Canada,
      were identified from the Ontario Cancer Registry. Patient records were linked
      deterministically to provincial health care databases to provide comprehensive
      medical follow-up. All patients received >= one cycle of adjuvant chemotherapy.
      Patient cases of EBC (n = 8,359) were matched to NCCs (n = 8,359) on age,
      comorbidity, and geographic location. ER + Hs within 30 days of chemotherapy were
      identified. If the primary reason for the visit was a common chemotherapy
      toxicity, the visit was considered chemotherapy associated. All-cause and
      chemotherapy-associated visits were compared between patient cases and controls.
      Logistic regression models were used to identify covariates associated with ER +
      Hs. RESULTS: The proportion of patients with at least one ER + H was
      significantly higher in patients with EBC undergoing chemotherapy compared with
      NCCs (43.4% v 9.4%; P < .001). Patients with EBC were also more likely to have
      multiple ER + Hs (17.9% v 2.4%; P < .001). On multivariable analysis,
      comorbidity, receiving a regimen containing docetaxel, and certain geographic
      regions were associated with increased odds of ER + Hs. CONCLUSION: ER + Hs are
      common among patients with EBC receiving chemotherapy and significantly higher
      than among controls. This represents a potential opportunity for quality
      improvement.

PMID- 25604598
TI  - Selective arylthiolane deprotection by singlet oxygen: a promising tool for
      sensors and prodrugs.
AB  - A routine thioketal protecting group reacts rapidly and selectively with singlet
      oxygen to reveal ketone products in good (aryl 1,3-dithiolane) to excellent (aryl
      1,3-oxathiolane) yields. Arylthiolanes are stable to biologically relevant
      reactive oxygen species and can be used as a light-activated gating mechanism for
      activating fluorescent sensors or small molecule prodrugs. 

PMID- 25604599
TI  - Transfemoral Transcatheter Aortic Valve Replacement in a Patient With Heparin
      Induced Thrombocytopenia: Intraoperative Anticoagulation Management With
      Bivalirudin (Angiomax).

PMID- 25604600
TI  - Clinical strategies to prevent pulmonary complications in cardiac surgery: an
      overview.

PMID- 25604601
TI  - Can Mismatch Negativity Reduce Uncertainty in the Prediction of Awakening From
      Coma During Extracorporeal Membrane Oxygenation?

PMID- 25604602
TI  - Cardiac and Abdominal Pheochromocytomas: Anesthetic Management for a Combined
      Cardiac and Hepatobiliary Procedure.

PMID- 25604603
TI  - Reactivity of vinylidene complexes of ruthenium with hydrazines and
      hydroxylamines.
AB  - Vinylidene complexes [Ru(eta(5)-C5H5){[double bond, length as m-dash]C[double
      bond, length as m-dash]C(H)R}(PPh3)L]BPh4 (, ) [L = P(OMe)3, P(OEt)3; R = Ph, p
      tolyl, Bu(t), H] react with hydrazine R1NHNH2 (R1 = H, Me, Ph) to afford nitrile
      derivatives [Ru(eta(5)-C5H5)(N[triple bond, length as m-dash]CCH2R)(PPh3)L]BPh4
      (, ) and amine R1NH2. Hydroxylamine NH2OH also reacts with vinylidenes , to yield
      nitrile derivatives , and H2O. Studies with (15)N-labeled hydrazine and DFT
      calculations allowed a reaction path to be proposed. The complexes were
      characterized by spectroscopy (IR, (1)H, (31)P, (13)C and (15)N NMR) and by X-ray
      crystal structure determination of [Ru(eta(5)-C5H5)(N[triple bond, length as m
      dash]CCH2Ph)(PPh3){P(OEt)3}]BPh4 (). 

PMID- 25604604
TI  - Dose-response relationship study of selenium nanoparticles as an
      immunostimulatory agent in cancer-bearing mice.
AB  - BACKGROUNDS AND AIMS: Oral administration of selenium nanoparticles has an
      immunomodulatory effect on individuals with cancer. In the present study we aimed
      to compare the cancer preventive effect via administration of different doses of
      selenium nanoparticles in mice with cancer. METHODS: Forty 6- to 8-week-old
      inbred female BALB/c mice were used and divided into four test and control
      groups; each group contained ten mice. Group 1 (administered PBS) was used as the
      control and the test groups 2, 3, and 4 were daily administered 50, 100, and 200
      MUg of selenium nanoparticles, respectively, for 60 days. After 60 days, tumor
      induction was carried out and 10 days later serum samples were collected to
      measure the cytokines. Tumor growth and life span of the mice were also monitored
      during the study. RESULTS: The results showed a significant increase in serum IFN
      gamma and the ratio of IFN-gamma/IL-4 in all administered doses compared to
      control. In addition, in mice that received higher doses of selenium
      nanoparticles (200 MUg/day), lower tumor volume and extended life span were
      observed compared to control. Administration of selenium nanoparticles in normal
      mice without tumor challenge caused a nonsignificant increase in cytokine
      production, indicating that selenium supplementation has no effect on the immune
      response in the absence of tumor challenge. CONCLUSIONS: The 200-MUg dose of
      selenium nanoparticles can induce more efficient responses against breast tumors.

PMID- 25604605
TI  - Transitions of care in heart failure: a scientific statement from the American
      Heart Association.
AB  - In patients with heart failure (HF), use of 30-day rehospitalization as a
      healthcare metric and increased pressure to provide value-based care compel
      healthcare providers to improve efficiency and to use an integrated care
      approach. Transition programs are being used to achieve goals. Transition of care
      in the context of HF management refers to individual interventions and programs
      with multiple activities that are designed to improve shifts or transitions from
      one setting to the next, most often from hospital to home. As transitional care
      programs become the new normal for patients with chronic HF, it is important to
      understand the current state of the science of transitional care, as discussed in
      the available research literature. Of transitional care reports, there was much
      heterogeneity in research designs, methods, study aims, and program targets, or
      they were not well described. Often, programs used bundled interventions, making
      it difficult to discuss the efficiency and effectiveness of specific
      interventions. Thus, further HF transition care research is needed to ensure best
      practices related to economically and clinically effective and feasible
      transition interventions that can be broadly applicable. This statement provides
      an overview of the complexity of HF management and includes patient, hospital,
      and healthcare provider barriers to understanding end points that best reflect
      clinical benefits and to achieving optimal clinical outcomes. The statement
      describes transitional care interventions and outcomes and discusses implications
      and recommendations for research and clinical practice to enhance patient
      centered outcomes. 

PMID- 25604606
TI  - Barriers and enablers to implementing clinical treatment protocols for fever,
      hyperglycaemia, and swallowing dysfunction in the Quality in Acute Stroke Care
      (QASC) Project--a mixed methods study.
AB  - BACKGROUND: The Quality in Acute Stroke Care (QASC) trial evaluated systematic
      implementation of clinical treatment protocols to manage fever, sugar, and
      swallow (FeSS protocols) in acute stroke care. This cluster-randomised controlled
      trial was conducted in 19 stroke units in Australia. AIM: To describe perceived
      barriers and enablers preimplementation to the introduction of the FeSS protocols
      and, postimplementation, to determine which of these barriers eventuated as
      actual barriers. METHODS: Preimplementation: Workshops were held at the
      intervention stroke units (n = 10). The first workshop involved senior clinicians
      who identified perceived barriers and enablers to implementation of the
      protocols, the second workshop involved bedside clinicians. Postimplementation,
      an online survey with stroke champions from intervention sites was conducted.
      RESULTS: A total of 111 clinicians attended the preimplementation workshops,
      identifying 22 barriers covering four main themes: (a) need for new policies, (b)
      limited workforce (capacity), (c) lack of equipment, and (d) education and
      logistics of training staff. Preimplementation enablers identified were: support
      by clinical champions, medical staff, nursing management and allied health staff;
      easy adaptation of current protocols, care-plans, and local policies; and
      presence of specialist stroke unit staff. Postimplementation, only five of the 22
      barriers identified preimplementation were reported as actual barriers to
      adoption of the FeSS protocols, namely, no previous use of insulin infusions;
      hyperglycaemic protocols could not be commenced without written orders; medical
      staff reluctance to use the ASSIST swallowing screening tool; poor level of
      engagement of medical staff; and doctors' unawareness of the trial. LINKING
      EVIDENCE TO ACTION: The process of identifying barriers and enablers
      preimplementation allowed staff to take ownership and to address barriers and
      plan for change. As only five of the 22 barriers identified preimplementation
      were reported to be actual barriers at completion of the trial, this suggests
      that barriers are often overcome whilst some are only ever perceived rather than
      actual barriers.

PMID- 25604607
TI  - Fibroblast growth factor 19-targeted therapies for the treatment of metabolic
      disease.
AB  - INTRODUCTION: Fibroblast growth factors (FGFs) belong to the FGF superfamily with
      diverse biological functions, including proliferation, cellular differentiation,
      wound repair, angiogenesis and tumorigenesis. The ability to reduce liver fat
      content and concentrations of triglycerides, total cholesterol and plasma
      glucose, and to improve sensitivity and limit pro-lipogenic properties of
      insulin, makes FGF19 a promising therapeutic target for the treatment of
      metabolic syndrome. FGF19 regulates bile acid biosynthesis in the bile duct,
      glucose metabolism and vitamin D and phosphate homeostasis, raises the metabolic
      rate, reduces body weight, and ameliorates diabetes in mice. The therapeutic
      potential of FGF19 to treat metabolic disorders has been widely studied in animal
      models, but currently there are no reports concerning its use in humans. AREAS
      COVERED: The following article highlights the metabolic effects and mechanism of
      action of FGF19. It also discusses the potential therapies that target FGF19.
      EXPERT OPINION: FGF19 is emerging as a new target for the therapy of metabolic
      disorders, including diabetes. The results obtained from animal models are
      promising. However, there is still much to be done before the translation of
      these effects into practice will be possible.

PMID- 25604609
TI  - Optically active helical vinylterphenyl polymers: chiral teleinduction in radical
      polymerization and tunable stereomutation.
AB  - Helical vinyl aromatic polymers are emerging as interesting chiral materials due
      to their dynamic tailorability, synthetic simplicity, and outstanding chemical
      and physical stabilities. This Personal Account discusses long-range chirality
      transfer in the radical polymerization of vinylterphenyl monomers and tunable
      stereomutation of the resultant polymers. It begins with a general introduction
      to the design, synthesis, and characterization of helical poly{(+)-2,5-bis[4'
      ((S)-2-methylbutyloxy)phenyl]styrene}, the first one of this series of polymers.
      Then, long-range chirality transfer during radical polymerization of terphenyl
      based vinyl monomers is explained. After that, the chiroptical property control
      of the resultant polymers by means of the transition from kinetically controlled
      conformation to thermodynamically controlled conformation and external stimulus
      is described. This Personal Account concludes by discussing the advantages and
      disadvantages of the strategy of using vinylterphenyls to obtain optically active
      helical polymers and providing a short outlook, especially emphasizing the
      importance of tacticity on the chiroptical properties of polymers. 

PMID- 25604608
TI  - Antibody drug conjugates: design and selection of linker, payload and conjugation
      chemistry.
AB  - Antibody drug conjugates (ADCs) have emerged as an important pharmaceutical class
      of drugs designed to harness the specificity of antibodies with the potency of
      small molecule therapeutics. The three main components of ADCs are the antibody,
      the linker, and the payload; the majority of early work focused intensely on
      improving the functionality of these pieces. Recently, considerable attention has
      been focused on developing methods to control the site and number of linker/drug
      conjugated to the antibody, with the aim of producing more homogenous ADCs. In
      this article, we review popular conjugation methods and highlight recent
      approaches including "click" conjugation and enzymatic ligation. We discuss
      current linker technology, contrasting the characteristics of cleavable and non
      cleavable linkers, and summarize the essential properties of ADC payload,
      centering on chemotherapeutics. In addition, we report on the progress in
      characterizing to determine physicochemical properties and on advances in
      purifying to obtain homogenous products. Establishing a set of selection and
      analytical criteria will facilitate the translation of novel ADCs and ensure the
      production of effective biosimilars. 

PMID- 25604610
TI  - Treatment initiation factors and cognitive outcome in youth with perinatally
      acquired HIV infection.
AB  - OBJECTIVES: Although cognitive outcomes among perinatally infected youth have
      improved with highly active antiretroviral therapy (HAART), the impact of the age
      of initiation of treatment and the central nervous system (CNS) penetration
      effectiveness (CPE) of the regimen on cognitive outcomes is unknown. We aimed to
      describe the association between initiation age/regimen CPE score and cognitive
      outcomes in perinatally HIV-infected youth. METHODS: Linear regression was used
      to retrospectively assess the association between full-scale IQ score (FSIQ) and
      age of initiation of HAART, regimen CPE, and the presence/absence of an AIDS
      diagnosis before initiation of HAART in an urban US cohort. RESULTS: A total of
      88 of 181 subjects (48.6%) had an AIDS diagnosis. In 69, AIDS preceded the start
      of HAART. Mean FSIQ (mean age 155.4 months) was 86.3 [standard deviation (SD)
      15.6]. Neither age of initiation of HAART (P = 0.45) nor regimen CPE score (P =
      0.33) was associated with FSIQ. Mean FSIQ for patients with an AIDS diagnosis
      before HAART initiation [82 (SD 17.0)] was significantly lower than for patients
      initiating HAART before an AIDS diagnosis [90 (SD 13)] (P = 0.001). Of the 129
      subjects without AIDS by age 5 years, 41 (31.8%) initiated HAART before age 5
      years; four of 41 later developed AIDS, compared with 32 of 88 of those who did
      not initiate HAART before age 5 years. The relative risk of AIDS if HAART was
      initiated before age 5 years was 0.19 (95% confidence interval 0.05-0.60).
      CONCLUSIONS: Earlier age at HAART initiation and higher CPE score of a regimen
      did not improve cognitive outcomes. However, initiating HAART prior to AIDS
      protected against AIDS and was associated with a significantly higher FSIQ.

PMID- 25604611
TI  - Enhancing Consolidation of a New Temporal Motor Skill by Cerebellar Noninvasive
      Stimulation.
AB  - Cerebellar transcranial direct current stimulation (tDCS) has the potential to
      modulate cerebellar outputs and visuomotor adaptation. The cerebellum plays a
      pivotal role in the acquisition and control of skilled hand movements, especially
      its temporal aspects. We applied cerebellar anodal tDCS concurrently with
      training of a synchronization-continuation motor task. We hypothesized that
      anodal cerebellar tDCS will enhance motor skill acquisition. Cerebellar tDCS was
      applied to the right cerebellum in 31 healthy subjects in a double-blind, sham
      controlled, parallel design. During synchronization, the subjects tapped the
      sequence in line with auditory cues. Subsequently, in continuation, the learned
      sequence was reproduced without auditory cuing. Motor task performance was
      evaluated before, during, 90 min, and 24 h after training. Anodal cerebellar
      tDCS, compared with sham, improved the task performance in the follow-up tests
      (F1,28 = 5.107, P = 0.032) of the synchronization part. This effect on retention
      of the skill was most likely mediated by enhanced motor consolidation. We
      provided first evidence that cerebellar tDCS can enhance the retention of a fine
      motor skill. This finding supports the promising approach of using noninvasive
      brain stimulation techniques to restore impaired motor functions in neurological
      patients, such after a stroke. 

PMID- 25604612
TI  - Joints and their relations as critical features in action discrimination:
      evidence from a classification image method.
AB  - Classifying an action as a runner or a walker is a seemingly effortless process.
      However, it is difficult to determine which features are used with hypothesis
      driven research, because biological motion stimuli generally consist of about a
      dozen joints, yielding an enormous number of potential relationships among them.
      Here, we develop a hypothesis-free approach based on a classification image
      method, using experimental data from relatively few trials (~1,000 trials per
      subject). Employing ambiguous actions morphed between a walker and a runner, we
      identified three types of features that play important roles in discriminating
      bipedal locomotion presented in a side view: (a) critical joint feature,
      supported by the finding that the similarity of the movements of feet and wrists
      to prototypical movements of these joints were most reliably used across all
      participants; (b) structural features, indicated by contributions from almost all
      other joints, potentially through a form-based analysis; and (c) relational
      features, revealed by statistical correlations between joint contributions,
      specifically relations between the two feet, and relations between the
      wrists/elbow and the hips. When the actions were inverted, only critical joint
      features remained to significantly influence discrimination responses. When
      actions were presented with continuous depth rotation, critical joint features
      and relational features associated strongly with responses. Using a double-pass
      paradigm, we estimated that the internal noise is about twice as large as the
      external noise, consistent with previous findings. Overall, our novel design
      revealed a rich set of critical features that are used in action discrimination.
      The visual system flexibly selects a subset of features depending on viewing
      conditions. 

PMID- 25604613
TI  - Early cleavage of handmade cloned buffalo (Bubalus bubalis) embryos is an
      indicator of their developmental competence and quality.
AB  - Following IVF, embryos which cleave early have been shown to have higher
      developmental competence and quality than those that cleave relatively later
      across many species. We investigated the effect of time of cleavage on the
      developmental competence, quality, epigenetic status and gene expression in
      buffalo embryos produced by handmade cloning (HMC). Following classification of
      embryos as early cleaving (EC) or late cleaving (LC) based on whether they had
      cleaved or not at 24 h post in vitro culture, 54% (164/303) were found to be EC
      and the rest to be LC. The blastocyst rate (58.1 +/- 3.4 vs 36.9 +/- 1.6%, p <
      0.01) and the total cell number (285.5 +/- 41.9 vs 141.4 +/- 36.1, p < 0.05) were
      higher, whereas the apoptotic index (3.6 +/- 0.6 vs 12.2 +/- 1.7, p < 0.01) and
      the global level of H3K9ac and H3K27me3 were lower (p < 0.05) in the blastocysts
      produced from EC than in those produced from LC embryos. The relative transcript
      level of CASPASE3, CASPASE7, DNMT1, DNMT3a and CDX2 was higher (p < 0.05) and
      that of SOX2 was lower (p < 0.05) in blastocysts produced from LC than in those
      produced from EC embryos, whereas the expression level of CASPASE6, P53, P21,
      HDAC1, OCT4 and NANOG was not significantly different between the two groups.
      These results show that (i) following HMC, blastocysts produced from embryos that
      cleave early differ from those produced from late cleaving embryos in terms of
      epigenetic status and expression level of many important apoptosis-, pluripotency
      , trophectoderm- and epigenetics-related genes, and (ii) EC embryos are superior
      to LC embryos in view of their higher developmental competence and quality.

PMID- 25604614
TI  - Performance of different imaging modalities in assessment of response to
      neoadjuvant therapy in primary esophageal cancer.

PMID- 25604615
TI  - Postoperative endophthalmitis in Danish eye clinics.

PMID- 25604616
TI  - Footwear Experiences of People With Chronic Musculoskeletal Diseases.
AB  - OBJECTIVE: Foot pain and deformities are frequently reported by people with
      chronic musculoskeletal diseases, but only limited research has been conducted to
      explore the key issues concerning footwear difficulties in this population. The
      aim of this study is to explore, identify, and describe the main issues
      surrounding the footwear experiences of people with chronic musculoskeletal
      diseases. METHODS: A qualitative manifest content analysis of open-ended survey
      responses concerning footwear experiences was conducted from a national footwear
      survey of people with chronic musculoskeletal diseases in New Zealand. Eighty
      five respondents submitted usable responses. Specific statements in the text were
      identified as units of analysis prior to coding and organizing these units into
      emerging mutually exclusive categories. Content analysis was independently
      undertaken by 3 researchers, and the final categories and coding were achieved
      through consensus. Frequencies of assigned units of analysis were calculated in
      order to obtain a quantitative description for each category. RESULTS: Four
      categories encompassing a total of 9 subcategories related to the footwear
      experiences of respondents emerged from the qualitative data content analysis:
      difficulty finding appropriate footwear; dissatisfaction with therapeutic
      footwear provision and foot care access; high costs of footwear, foot care, and
      self-care; and satisfaction with therapeutic footwear and foot care. CONCLUSION:
      Key categories describing the important issues surrounding the footwear
      experiences of respondents with chronic musculoskeletal diseases were identified,
      which may provide important targets for improving footwear and foot care services
      and self-management strategies.

PMID- 25604617
TI  - Effect of ultrasonic homogenization on the Vis/NIR bulk optical properties of
      milk.
AB  - The size of colloidal particles in food products has a considerable impact on the
      product's physicochemical, functional and sensory characteristics. Measurement
      techniques to monitor the size of suspended particles could, therefore, help to
      further reduce the variability in production processes and promote the
      development of new food products with improved properties. Visible and near
      infrared (Vis/NIR) spectroscopy is already widely used to measure the composition
      of agricultural and food products. However, this technology can also be consulted
      to acquire microstructure-related scattering properties of food products. In this
      study, the effect of the fat globule size on the Vis/NIR bulk scattering
      properties of milk was investigated. Variability in fat globule size distribution
      was created using ultrasonic homogenization of raw milk. Reduction of the fat
      globule size resulted in a higher wavelength-dependency of both the Vis/NIR bulk
      scattering coefficient and the scattering anisotropy factor. Moreover, the
      anisotropy factor and the bulk scattering coefficients for wavelengths above 600
      nm were reduced and were dominated by Rayleigh scattering. Additionally, the bulk
      scattering properties could be well (R(2) >= 0.990) estimated from measured
      particle size distributions by consulting an algorithm based on the Mie solution.
      Future research could aim at the inversion of this model to estimate the particle
      size distributions from Vis/NIR spectroscopic measurements.

PMID- 25604618
TI  - Refsum Disease Presenting with a Late-Onset Leukodystrophy.
AB  - Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized
      by phytanic acid storage. Clinical symptoms usually begin in late childhood
      before the age of 20. Typical clinical presentation includes nyctalopia caused by
      retinitis pigmentosa, and anosmia. After 10-15 years, deafness, cerebellar
      ataxia, polyneuropathy, ichthyosis, and cardiac arrhythmia can occur.We report
      the case of a very late-onset adult Refsum disease presenting with marked
      cognitive decline and severe leukoencephalopathy, without peripheral nervous
      system involvement. Brain MRI showed a leukoencephalopathy involving the
      periventricular white matter, subcortical area, and the brainstem with relative
      sparing of juxtacortical U fibers. This was associated with severe cortical and
      subcortical atrophy with ventricle dilatation. MR spectroscopy showed a marked
      increase in the choline/NAA ratio. Elevated plasma phytanic acid level was found,
      whereas plasma levels of pristanic and very long chain fatty acids were normal.
      The patient is homozygous for a previously undescribed PHYH frameshift mutation.
      Whether the very unusual phenotype is related to this peculiar mutation remains
      unclear. 

PMID- 25604620
TI  - Expedient synthesis of tetrasubstituted pyrroles via a copper-catalyzed cascade
      inter-/intramolecular cyclization of 1,3-enynes carry a nitro group with amines.
AB  - Various tetrasubstituted pyrroles/pyrazoles have been prepared from nitro
      substituted 1,3-enynes with aromatic amines/hydrazines via a copper-catalyzed
      cascade aza-Michael addition, cyclization and aromatization at room temperature.
      This protocol is also effective for the synthesis of tetrasubstituted pyrazoles
      in high yields. 

PMID- 25604619
TI  - Making the White Matter Matters: Progress in Understanding Canavan's Disease and
      Therapeutic Interventions Through Eight Decades.
AB  - Canavan's disease (CD) is a fatal autosomal recessive pediatric leukodystrophy in
      which patients show severe neurodegeneration and typically die by the age of 10,
      though life expectancy in patients can be highly variable. Currently, there is no
      effective treatment for CD; however, gene therapy seems to be a feasible approach
      to combat the disease. Being a monogenic defect, the disease provides an
      excellent model system to develop gene therapy approaches that can be extended to
      other monogenic leukodystrophies and neurodegenerative diseases. CD results from
      mutations in a single gene aspartoacylase which hydrolyses N-acetyl aspartic acid
      (NAA) which accumulates in its absences. Since CD is one of the few diseases that
      show high NAA levels, it can also be used to study the enigmatic biological role
      of NAA. The disease was first described in 1931, and this review traces the
      progress made in the past 8 decades to understand the disease by enumerating
      current hypotheses and ongoing palliative measures to alleviate patient symptoms
      in the context of the latest advances in the field. 

PMID- 25604622
TI  - Diffusion and partitioning of macromolecules in casein microgels: evidence for
      size-dependent attractive interactions in a dense protein system.
AB  - Understanding the mechanisms that determine the diffusion and interaction of
      macromolecules (such as proteins and polysaccharides) that disperse through dense
      media is an important fundamental issue in the development of innovative
      technological and medical applications. In the current work, the partitioning and
      diffusion of macromolecules of different sizes (from 4 to 10 nm in diameter) and
      shapes (linear or spherical) within dispersions of casein micelles (a protein
      microgel) is studied. The coefficients for diffusion and partition are measured
      using FRAP (fluorescence recovery after photobleaching) and analyzed with respect
      to the structural characteristics of the microgel determined by the use of TEM
      (transmission electron microscopy) tomography. The results show that the casein
      microgel displays a nonspecific attractive interaction for all macromolecules
      studied. When the macromolecular probes are spherical, this affinity is clearly
      size-dependent, with stronger attraction for the larger probes. The current data
      show that electrostatic effects cannot account for such an attraction. Rather,
      nonspecific hydration molecular forces appear to explain these results. These
      findings show how weak nonspecific forces affect the diffusion and partitioning
      of proteins and polysaccharides in a dense protein environment. These results
      could be useful to better understand the mechanisms of diffusion and partitioning
      in other media such as cells and tissues. Furthermore, there arises the
      possibility of using the casein micelle as a size-selective molecular device. 

PMID- 25604621
TI  - Impact of hybrid procedure on P wave duration for atrial fibrillation ablation.
AB  - AIM: Hybrid procedure (HP) involves epicardial isolation of pulmonary vein and
      posterior wall of left atrium, and endocardial checking of lesions and touchups
      (if needed). We aimed at observing the effect of hybrid procedure on P wave
      duration (PWD), calculated automatically from surface ECG leads at start and end
      of HP, and also for relationship to atrial fibrillation (AF) recurrence at 9
      months. METHODS: Forty-one patients (32 male; mean age, 58.4 +/- 9.5 years)
      underwent HP, as first ever ablation. A new automated method was used for P wave
      segmentation and PWD estimation from recognizable P waves in ECG lead I or II
      before and after HP, based on fitting of each P wave by means of two Gaussian
      functions. RESULTS: Overall, PWD was significantly decreased after procedure
      (104.4 +/- 25.1 ms vs. 84.7 +/- 23.8 ms, p = 0.0151), especially in persistent AF
      patients (122.4 +/- 32.2 ms vs. 85.6 +/- 24.5 ms, p = 0.02). PWD preprocedure was
      significantly higher in persistent than in paroxysmal patients (122.4 +/- 32.2 ms
      vs. 92.5 +/- 17.9 ms, p = 0.0383). PWD was significantly decreased after
      procedure in prior electrical cardioverted patients (106.7 +/- 30.5 ms vs. 84.7
      +/- 23.1 ms, p = 0.0353). After 9-month follow-up of 40 patients, HP-induced PWD
      decrease was significant for the 12 persistent patients without recurrence
      (122.4.1 +/- 35.3 ms vs. 85.6 +/- 22.0 ms, p = 0.0210). CONCLUSION: Preprocedure
      PWD was higher for persistent than paroxysmal patients. HP reduced PWD
      significantly. Nine-month follow-up suggests that HP is successful in restoring
      and maintaining sinus rhythm. To individualize AF therapy, AF type-based
      selection of patients may be possible before procedure. Automated analysis of PWD
      from surface ECG is possible.

PMID- 25604623
TI  - Familial colorectal cancer risk by subsite of primary cancer: a population-based
      study in Utah.
AB  - BACKGROUND: Familial occurrence is common in colorectal cancer (CRC), but whether
      this increased familial risk differs by colonic subsite of the index patients CRC
      is not well understood. AIM: To quantify the risk of CRC in first-degree (FDR),
      second-degree (SDR) and first cousin (FC) relatives of individuals with CRC,
      stratified by subsite in the colorectum and age at diagnosis. METHODS: Colorectal
      cancers diagnosed between 1980 and 2010 were identified from the Utah Cancer
      Registry and linked to pedigrees from the Utah Population Database. Age and
      gender-matched CRC-free controls were selected to form the comparison group for
      determining CRC risk in relatives using Cox regression analysis. RESULTS: Of the
      18,208 index patients diagnosed with CRC, 6584 (36.2%) were located in the
      proximal colon, 5986 (32.9%) in the distal colon and 5638 (31%) in the rectum.
      The elevated risk of CRC in relatives was similar in analysis stratified for CRC
      colorectal subsites in the index cases. FDR had similarly elevated risk of all
      site CRC, whether the index patient had cancer in the proximal colon [hazards
      ratio (HR): 1.85; 95% CI: 1.70-2.02], distal colon (HR: 1.90; 95% CI: 1.73-2.08)
      or rectum (HR: 1.83; 95% CI: 1.66-2.02) compared to relatives of controls. This
      risk was consistently greater for FDR when cases developed CRC below the age of
      60 years. CONCLUSIONS: Relatives of CRC patients have a similarly elevated risk
      of CRC regardless of colonic tumour subsite in the index patient, and it is
      greatest for relatives of younger age index cases.

PMID- 25604625
TI  - The Dental Health of primary school children living in fluoridated, pre
      fluoridated and non-fluoridated communities in New South Wales, Australia.
AB  - BACKGROUND: The Local Government Area of Gosford implemented a water fluoridation
      scheme in 2008. Therefore the opportunity was taken to record the dental health
      of primary school children aged 5-7 years prior to the fluoridation and compare
      the results with other communities in NSW with different access to fluoridated
      water. The aim was to compare the oral health of New South Wales (Australia)s 5-7
      year olds living in fluoridated, and non- fluoridated communities. One of the
      areas was due to implement water fluoridation and is termed the pre-fluoridation
      site. METHODS: Pupils in the first year of Public and Catholic Schools in three
      areas of NSW were recruited. Class lists were used to draw a sample of
      approximately 900 per area. This number allowed for a non-response rate of up to
      30 per cent and would give a sample sufficient numbers to allow statistical
      inferences to be drawn. Children whose parents consented received a dental
      examination and the clinical data was collected on mark sense cards. RESULTS: In
      the 3 areas the proportion of children who received a dental examination varied;
      77.5% (n = 825) for the fluoridated area, 80.1% (n = 781) for the pre-fluoridated
      area and 55.3% (n = 523) for the non-fluoridated area. The mean dmft was 1.40 for
      the fluoridated area, 2.02 for the pre-fluoridated area and 2.09 for the non
      fluoridated area. These differences were statistically significant (p < 0.01).
      Differences were also noted in the proportion of children who were caries free,
      62.6% fluoridated area, 50.8% for the pre-fluoride area and 48.6% for the non
      fluoride location. CONCLUSION: The children living in the well-established
      fluoridated area had less dental caries and a higher proportion free from disease
      when compared with the other two areas which were not fluoridated. Fluoridation
      demonstrated a clear benefit in terms of better oral health for young children.

PMID- 25604624
TI  - In vivo regulation of gene expression and T helper type 17 differentiation by
      RORgammat inverse agonists.
AB  - The orphan nuclear receptor, retinoic acid receptor-related orphan nuclear
      receptor gammat (RORgammat), is required for the development and pathogenic
      function of interleukin-17A-secreting CD4(+) T helper type 17 (Th17) cells.
      Whereas small molecule RORgammat antagonists impair Th17 cell development and
      attenuate autoimmune inflammation in vivo, the broader effects of these
      inhibitors on RORgammat-dependent gene expression in vivo has yet to be
      characterized. We show that the RORgammat inverse agonist TMP778 acts potently
      and selectively to block mouse Th17 cell differentiation in vitro and to impair
      Th17 cell development in vivo upon immunization with the myelin antigen MOG35-55
      plus complete Freund's adjuvant. Importantly, we show that TMP778 acts in vivo to
      repress the expression of more than 150 genes, most of which fall outside the
      canonical Th17 transcriptional signature and are linked to a variety of
      inflammatory pathologies in humans. Interestingly, more than 30 genes are related
      with SMAD3, a transcription factor involved in the Th17 cell differentiation.
      These results reveal novel disease-associated genes regulated by RORgammat during
      inflammation in vivo, and provide an early read on potential disease indications
      and safety concerns associated with pharmacological targeting of RORgammat. 

PMID- 25604626
TI  - Structural determinants of polyglutamine protofibrils and crystallites.
AB  - Nine inherited neurodegenerative diseases are associated with the expansion of
      the CAG codon. Once the translated polyglutamine expansion becomes longer than
      ~36 residues, it triggers the formation of intraneural protein aggregates that
      often display the signature of cross-beta amyloid fibrils. Here, we use fully
      atomistic molecular dynamics simulations to probe the structural stability and
      conformational dynamics of both previously proposed and new polyglutamine
      aggregate models. We test the relative stability of parallel and antiparallel
      beta sheets, and characterize possible steric interfaces between neighboring
      sheets and the effects of different alignments of the side-chain carboxamide
      dipoles. Results indicate that (i) different initial oligomer structures converge
      to crystals consistent with available diffraction data, after undergoing
      cooperative side-chain rotational transitions and quarter-stagger displacements
      on a microsecond time scale, (ii) structures previously deemed stable on a
      hundred nanosecond time scale are unstable over the microsecond time scale, and
      (iii) conversely, structures previously deemed unstable did not account for the
      correct side-chain packing and once the correct symmetry is considered the
      structures become stable for over a microsecond, due to tightly interdigitated
      side chains, which lock into highly regular polar zippers with inter-side-chain
      and backbone-side-chain hydrogen bonds. With these insights, we built Q40
      monomeric models with different combinations of arc and hairpin turns and tested
      them for stability. The stable monomers were further probed as a function of
      repeat length. Our results are consistent with the aggregation threshold. These
      results explain and reconcile previously reported experimental and model
      discrepancies about polyglutamine aggregate structures.

PMID- 25604627
TI  - Smart, reusable labels for assessing self-cleaning films.
AB  - Novel, reversible (reusable) photocatalyst activity indicator labels, which
      undergo a rapid colour change when in contact with a photocatalytic film via the
      photoreduction of methylene blue contained within the label's adhesive, are
      explored as a method for assessing the activity of self-cleaning glass in situ
      and the laboratory, using digital photography. 

PMID- 25604628
TI  - Phenolic content, antioxidant and anti-inflammatory activities of Tunisian
      Diplotaxis simplex (Brassicaceae).
AB  - This study investigates the polyphenol content of Diplotaxis simplex extract and
      the biological activities of the main organ. The analysed extracts showed that
      polyphenol contents varied considerably as a function of organs. Furthermore,
      novel biological activities of this species were assessed. Flower extracts
      exhibit a potent in vitro antioxidant capacity using oxygen radical absorbance
      capacity and displayed a strong anti-inflammatory activity, inhibiting nitric
      oxide release, by 79.3% at 160 MUg/mL. Our findings suggested that the Diplotaxis
      flower is a valuable source of antioxidants and anti-inflammatory agents.

PMID- 25604629
TI  - How well do birth records serve maternal and child health programs? Birth
      registration system evaluation, New York City, 2008-2011.
AB  - National birth registration guidelines were revised in 2003 to improve data
      quality; however, few studies have evaluated the impact on local jurisdictions
      and their data users. In New York City (NYC), approximately 125,000 births are
      registered annually with the NYC Department of Health and Mental Hygiene, and
      data are used routinely by the department's maternal and child health (MCH)
      programs. In order to better meet MCH program needs, we used Centers for Disease
      Control and Prevention guidelines to assess birth data usefulness, simplicity,
      data quality, timeliness and representativeness. We interviewed birth
      registration and MCH program staff, reviewed a 2009 survey of birth registrars (n
      = 39), and analyzed 2008-2011 birth records for timeliness and completeness (n =
      502,274). Thirteen MCH programs use birth registration data for eligibility
      determination, needs assessment, program evaluation, and surveillance.
      Demographic variables are used frequently, nearly 100 % complete, and considered
      the gold standard by programs; in contrast, medical variables' use and validity
      varies widely. Seventy-seven percent of surveyed birth registrars reported >=1
      problematic items in the system; 64.1 % requested further training. During 2008
      2011, the median interval between birth and registration was 5 days (range 0-260
      days); 11/13 programs were satisfied with timeliness. The NYC birth registration
      system provides local MCH programs useful, timely, and representative data.
      However, some medical items are difficult to collect, of low quality, and rarely
      used. We recommend enhancing training for birth registrars, continuing quality
      improvement efforts, increasing collaboration with program users, and removing
      consistently low-quality and low-use variables.

PMID- 25604631
TI  - Evaluating Measurement Invariance Between Parents Using the Strengths and
      Difficulties Questionnaire (SDQ).
AB  - Parent ratings of their children's behavioral and emotional difficulties are
      commonly collected via the Strength and Difficulties Questionnaire (SDQ). For the
      first time, this study addressed the issue of interparent agreement using a
      measurement invariance approach. Data from 695 English couples (mothers and
      fathers) who had rated the behavior of their 4.25-year-old child were used. Given
      the inconsistency of previous results about the SDQ factor structure, alternative
      measurement models were tested. A five-factor Exploratory Structural Equation
      Model allowing for nonzero cross-loadings fitted data best. Subsequent invariance
      analyses revealed that the SDQ factor structure is adequately invariant across
      parents, with interrater correlations ranging from .67 to .78. Fathers reported
      significantly higher levels of child conduct problems, hyperactivity, and
      emotional symptoms, and lower levels of prosocial behavior. This suggests that
      mothers and fathers each provide unique information across a range of their
      child's behavioral and emotional problems. 

PMID- 25604632
TI  - Induced lung inflammation and dietary protein supply affect nitrogen retention
      and amino acid metabolism in growing pigs.
AB  - It is hypothesised that during immune system activation, there is a competition
      for amino acids (AA) between body protein deposition and immune system
      functioning. The aim of the present study was to quantify the effect of immune
      system activation on N retention and AA metabolism in growing pigs, depending on
      dietary protein supply. A total of sixteen barrows received an adequate (Ad) or
      restricted (Res) amount of dietary protein, and were challenged at day 0 with
      intravenous complete Freund's adjuvant (CFA). At days - 5, 3 and 8, an
      irreversible loss rate (ILR) of eight AA was determined. CFA successfully
      activated the immune system, as indicated by a 2- to 4-fold increase in serum
      concentrations of acute-phase proteins (APP). Pre-challenge C-reactive protein
      concentrations were lower (P< 0.05) and pre- and post-challenge albumin tended to
      be lower in Res-pigs. These findings indicate that a restricted protein supply
      can limit the acute-phase response. CFA increased urinary N losses (P= 0.04) and
      tended to reduce N retention in Ad-pigs, but not in Res-pigs (P= 0.07). The ILR
      for Val was lower (P= 0.05) at day 8 than at day 3 in the post-challenge period.
      The ILR of most AA, except for Trp, were strongly affected by dietary protein
      supply and positively correlated with N retention. The correlations between the
      ILR and APP indices were absent or negative, indicating that changes in AA
      utilisation for APP synthesis were either not substantial or more likely
      outweighed by a decrease in muscle protein synthesis during immune system
      activation in growing pigs. 

PMID- 25604630
TI  - Diagnosis and Characterization of DSM-5 Nonsuicidal Self-Injury Disorder Using
      the Clinician-Administered Nonsuicidal Self-Injury Disorder Index.
AB  - Despite the inclusion of nonsuicidal self-injury disorder (NSSID) in the DSM-5,
      research on NSSID is limited and no studies have examined the full set of DSM-5
      NSSID diagnostic criteria. Thus, this study examined the reliability and validity
      of a new structured diagnostic interview for NSSID (the Clinician-Administered
      NSSI Disorder Index; CANDI) and provides information on the clinical
      characteristics and features of DSM-5 NSSID. Data on the interrater reliability,
      internal consistency, and construct validity of the CANDI and associated
      characteristics of NSSID were collected in a community sample of young adults (N
      = 107) with recent recurrent NSSI (>=10 lifetime episodes of NSSI, at least one
      episode in the past year). Participants completed self-report measures of NSSI
      characteristics, psychopathology, and emotion dysregulation, as well as
      diagnostic interviews of borderline personality disorder (BPD) and lifetime mood,
      anxiety, and substance use disorders. The CANDI demonstrated good interrater
      reliability and adequate internal consistency. Thirty-seven percent of
      participants met criteria for NSSID. NSSID was associated with greater clinical
      and diagnostic severity, including greater NSSI versatility, greater emotion
      dysregulation and psychopathology, and higher rates of BPD, bipolar disorder,
      posttraumatic stress disorder, social anxiety disorder, and alcohol dependence.
      Findings provide support for the reliability, validity, and feasibility of the
      CANDI. 

PMID- 25604633
TI  - Association of the long pentraxin PTX3 gene polymorphism (rs3816527) with
      migraine in an Iranian population.
AB  - BACKGROUND: Migraine is a common neurovascular disorder with multifactorial and
      polygenic inheritance. It has been shown that migraine may be a form of sterile
      neurogenic inflammation. Pentaxins 3 (PTX3) has been detected in brain during
      inflammatory responses. The aim of our study was to investigate the association
      of rs3816527 polymorphism of the PTX3 gene and migraine in an Iranian population.
      METHOD: We included 103 newly diagnosed migraine patients and 148 healthy
      subjects as control group. Genomic DNA samples extracted from the peripheral
      blood and genotypes of PTX3 rs3816527 gene polymorphism were determined. The
      patients filled out HIT-6 questionnaire as a scale to evaluate the severity of
      headache. RESULTS: The genotype frequency of PTX3 was significantly different
      between the migraine patients and the control subjects. CC variant homozygote
      genotype was statistically more frequent in the patients than in the controls
      (P<0.05; OR=1.74, 95% CI=1.04-2.94). Also the C allele was not significantly more
      frequent in the patients (P=0.096; OR=1.27, 95% CI=0.88-1.85). A separate
      analysis in male and female subjects showed no significant differences between
      the different genotypes and phenotypes of PTX3 rs3816527 gene and susceptibility
      to migraine in female subjects. Total HIT-6 score was significantly different
      between three PTX3 genotypes (P=0.008). CONCLUSION: In conclusion our results
      showed the association between the PTX3 rs3816527 gene polymorphism with
      susceptibility to migraine only in the male patients. Also total HIT-6 scores as
      a scale for assessment of the severity were related to the PTX3 rs3816527 gene
      polymorphism. But this relation was not established by headache frequency.

PMID- 25604634
TI  - The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene
      is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01
      negative individuals.
AB  - C-C chemokine receptor 2 (CCR2) is one of the key players involved in the
      transmigration of mononuclear cells into the central nervous system (CNS) and
      subsequent development of multiple sclerosis (MS). The aim of the current study
      was to analyse the association of CCR2 +190 G/A (rs1799864) polymorphism with
      susceptibility to MS and its influence on the age at onset, severity and
      neurological disability in MS. CCR2 genotyping was carried out by a polymerase
      chain reaction with restriction fragment length polymorphism (PCR-RFLP) in 301 MS
      patients and 342 healthy controls. Logistic regression analysis suggested a
      marginally significant association between MS and rs1799864 A allele (AA+GA vs.
      GG, P=0.047, OR=1.50, 95% CI=1.00-2.25), however, after stratification of study
      groups for the presence of HLA-DRB1*15:01 risk allele, this association could be
      found in HLA-DRB1*15:01-negative individuals only (AA+GA vs. GG, P=0.014,
      OR=1.84, 95% CI=1.13-2.98). Furthermore, there was no association between CCR2
      polymorphism and clinical features of MS. In conclusion, our results suggest that
      CCR2 +190 G/A polymorphism may increase the susceptibility to MS, but its action
      seems to be restricted to individuals who do not possess the major risk allele
      HLA-DRB1*15:01. 

PMID- 25604635
TI  - Internal biliary stenting during orthotopic liver transplantation: anastomotic
      complications, post-transplant biliary interventions, and survival.
AB  - BACKGROUND: Biliary complications are a leading source of surgical morbidity
      following orthotopic liver transplantation (OLT). METHODS: We examined how
      prophylactic internal biliary stent placement during OLT affected post-transplant
      morbidity and mortality in a single-center retrospective cohort study of 513
      recipients (2006-2012). Recipient and donor covariates were collected. Biliary
      complications included major and minor anastomotic leaks, strictures, or
      stenoses. Multivariate regression models were created to estimate how operative
      biliary stents affected outcomes. RESULTS: About 87.3% (n = 448) of recipients
      had a duct-to-duct biliary anastomosis, and 43.1% (n = 221) had biliary stents
      placed. The biliary complication rate was <15% at five yr, and 44.8% (n = 230)
      overall. Stenting was not protective from anastomotic biliary complications (p =
      0.06). Stenting was associated with a 74% higher adjusted risk of needing
      multiple endoscopic retrograde cholangiographies (ERCs; odds ratio [OR] 1.74, p =
      0.011), and trended toward a lower adjusted risk for repetitive percutaneous
      transhepatic cholangiography (PTCs; OR 0.56, p = 0.063). Stenting had no effect
      on the cumulative freedom from biliary complications (p = 0.94). Biliary
      complications were associated with mortality (HR 1.86, p = 0.014) and was
      unaffected by stenting (aHR = 0.72, p = 0.246). CONCLUSIONS: Biliary stenting
      during OLT does not deter biliary complications and is associated with higher
      risk of multiple invasive biliary interventions, particularly ERCs. Surgeons
      should evaluate the utility of biliary stents at OLT within this context.

PMID- 25604636
TI  - The use of mentalization-based treatment for adolescents (MBT-A) with a young
      woman with mixed personality disorder and tendencies to self-harm.
AB  - This article explores the psychological profile and treatment of young people who
      present clinically with features of borderline and avoidant personality disorder,
      along with vulnerable narcissistic traits. Self-harm in these youngsters is often
      used to regulate internal storms. It is argued that the adolescent phase of
      development is a trigger point for collapse in these vulnerable young people. In
      therapy, these patients are difficult to connect with emotionally and treatment
      can be fraught with strong countertransference reactions. A case study is used to
      illustrate the use of mentalization-based treatment for adolescents for such
      individuals. 

PMID- 25604639
TI  - Editor's note.

PMID- 25604637
TI  - Improved antioxidant activity in transgenic Perilla frutescens plants via
      overexpression of the gamma-tocopherol methyltransferase (gamma-tmt) gene.
AB  - The main goal of this study was to generate transgenic Perilla frutescens with
      enhanced antioxidant properties by overexpressing the gamma-tocopherol
      methyltransferase (gamma-tmt) gene. In this study, the antioxidant activity of
      methanolic crude extracts of transgenic and non-transgenic control plants was
      investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      method. Free radical scavenging activity was evaluated using alpha-tocopherol and
      butylated hydroxyl toluene as standard antioxidants. In general, the ethyl
      acetate fraction of transgenic P. frutescens showed stronger DPPH radical
      scavenging activity than the ethyl acetate fraction from non-transgenic control
      plants (IC50 2.00 +/- 0.10 and 5.53 +/- 0.40 MUg ? ml(-1), respectively). High
      performance liquid chromatography analysis of phenolic acids in leaf extracts
      confirmed increased levels of 16 individual phenolic compounds in two transgenic
      lines (pf47-5 and pf47-8) compared with control plants. Changes in the phenolic
      compound profile and alpha-tocopherol content were correlated with the
      antioxidant properties of transgenic plants, indicating that the introduction of
      transgene gamma-tmt influenced the metabolism of phenolic compounds and
      subsequently produced biochemical changes in the transformants. There were no
      significant differences in photosynthetic rate in the transgenic plants as
      compared to the non-transgenic control plants, suggesting that the alteration of
      phenolic compounds and tocopherol composition had little impact on
      photosynthesis.

PMID- 25604640
TI  - Validity of electronic diet recording nutrient estimates compared to dietitian
      analysis of diet records: randomized controlled trial.
AB  - BACKGROUND: Dietary intake assessment with diet records (DR) is a standard
      research and practice tool in nutrition. Manual entry and analysis of DR is time
      consuming and expensive. New electronic tools for diet entry by clients and
      research participants may reduce the cost and effort of nutrient intake
      estimation. OBJECTIVE: To determine the validity of electronic diet recording, we
      compared responses to 3-day DR kept by Tap & Track software for the Apple iPod
      Touch and records kept on the Nutrihand website to DR coded and analyzed by a
      research dietitian into a customized US Department of Agriculture (USDA) nutrient
      analysis program, entitled GRAND (Grand Forks Research Analysis of Nutrient
      Data). METHODS: Adult participants (n=19) enrolled in a crossover-designed
      clinical trial. During each of two washout periods, participants kept a written 3
      day DR. In addition, they were randomly assigned to enter their DR in a Web-based
      dietary analysis program (Nutrihand) or a handheld electronic device (Tap &
      Track). They completed an additional 3-day DR and the alternate electronic diet
      recording methods during the second washout. Entries resulted in 228 daily diet
      records or 12 for each of 19 participants. Means of nutrient intake were
      calculated for each method. Concordance of the intake estimates were determined
      by Bland-Altman plots. Coefficients of determination (R(2)) were calculated for
      each comparison to assess the strength of the linear relationship between
      methods. RESULTS: No significant differences were observed between the mean
      nutrient values for energy, carbohydrate, protein, fat, saturated fatty acids,
      total fiber, or sodium between the recorded DR analyzed in GRAND and either
      Nutrihand or Tap & Track, or for total sugars comparing GRAND and Tap & Track.
      Reported values for total sugars were significantly reduced (P<.05) comparing
      Nutrihand to GRAND. Coefficients of determination (R(2)) for Nutrihand and Tap &
      Track compared to DR entries into GRAND, respectively, were energy .56, .01;
      carbohydrate .58, .08; total fiber .65, .37; sugar .78, .41; protein .44, .03;
      fat .36, .03; saturated fatty acids .23, .03; sodium .20, .00; and for Nutrihand
      only for cholesterol .88; vitamin A .02; vitamin C .37; calcium .05; and iron
      .77. Bland-Altman analysis demonstrates high variability in individual responses
      for both electronic capture programs with higher 95% limits of agreement for
      dietary intake recorded on Tap & Track. CONCLUSIONS: In comparison to dietitian
      entered 3-day DR, electronic methods resulted in no significant difference in
      mean nutrient estimates but exhibited larger variability, particularly the Tap &
      Track program. However, electronic DR provided mean estimates of energy,
      macronutrients, and some micronutrients, which approximated those of the
      dietitian-analyzed DR and may be appropriate for dietary monitoring of groups.
      Electronic diet assessment methods have the potential to reduce the cost and
      burden of DR analysis for nutrition research and clinical practice. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01183520;
      http://clinicaltrials.gov/ct2/show/NCT01183520 (Archived by WebCite at
      http://www.webcitation.org/6VSdYznKX).

PMID- 25604642
TI  - The scope and control of attention: Sources of variance in working memory
      capacity.
AB  - Working memory capacity is a strong positive predictor of many cognitive
      abilities, across various domains. The pattern of positive correlations across
      domains has been interpreted as evidence for a unitary source of inter-individual
      differences in behavior. However, recent work suggests that there are multiple
      sources of variance contributing to working memory capacity. The current study (N
      = 71) investigates individual differences in the scope and control of attention,
      in addition to the number and resolution of items maintained in working memory.
      Latent variable analyses indicate that the scope and control of attention reflect
      independent sources of variance and each account for unique variance in general
      intelligence. Also, estimates of the number of items maintained in working memory
      are consistent across tasks and related to general intelligence whereas estimates
      of resolution are task-dependent and not predictive of intelligence. These
      results provide insight into the structure of working memory, as well as
      intelligence, and raise new questions about the distinction between number and
      resolution in visual short-term memory. 

PMID- 25604641
TI  - GPR39 marks specific cells within the sebaceous gland and contributes to skin
      wound healing.
AB  - G protein-coupled receptors (GPCRs) mediate multiple key biological processes in
      the body. The orphan receptor GPR39 has been reported to be involved in various
      pathophysiological events. However, the function of GPR39 in skin biology remains
      unknown. Using a genetically engineered mouse strain in which lacZ expression
      faithfully replaced endogenous Gpr39 expression, we discovered a unique
      expression pattern of Gpr39 in the sebaceous gland (SG). Using various methods,
      we confirmed that GPR39 marked a specific cell population at the opening of the
      SG and colocalised with the SG stem cell marker Blimp1. Further investigations
      showed that GPR39 was spatiotemporally expressed during skin wound repair.
      Although it was dispensable for skin development and homeostasis, GPR39
      contributed positively to skin wound healing: its loss led to a delay in wound
      healing during the intermediate stage. The present study reveals a novel role of
      GPR39 in both dermatology and stem cell biology that has not been previously
      recognised. 

PMID- 25604643
TI  - The involvement of working memory and inhibition functions in the different
      phases of insight problem solving.
AB  - In this article, the involvement of working memory capacity and inhibition
      functions in different phases of insight problem solving is investigated, by
      employing a method of separating the different phases of insight problem solving
      directly, on the basis of the subjects' oral reports. Two experiments are
      described. In Experiment 1, 87 subjects were administered a series of working
      memory span tasks and inhibition tasks, as well as a verbal insight problem. In
      Experiment 2, 119 subjects were administered the same working memory span tasks
      and inhibition tasks as in the first experiment, as well as a spatial insight
      problem. Several conclusions can be drawn from this study. First, the insight
      problem-solving process can be divided into several relatively independent
      phases, including an initial searching phase and a restructuring phase. Second,
      executive functions, as measured by working memory capacity, influence mainly the
      initial searching phase, rather than the restructuring phase. Third, inhibition
      functions play important but complex roles in restructuring, and sometimes could
      influence restructuring in contradictory ways simultaneously. The implications
      and value of this study are discussed further. 

PMID- 25604644
TI  - The intergenerational continuity of breastfeeding intention, initiation, and
      duration: a systematic review.
AB  - BACKGROUND: In studies investigating predictors of breastfeeding behaviors, it is
      not uncommon for researchers to adjust for participants' having been breastfed as
      an infant. This assumes an intergenerational effect of breastfeeding continuity.
      Our aim was to investigate the veracity of that assumption. Specifically, we
      sought to summarize and evaluate evidence of associations between breastfeeding
      in one generation and breastfeeding intentions and behaviors in the second
      generation. METHODS: A systematic search of psychological, nursing, and medical
      databases was conducted for studies examining "having been breastfed" as a factor
      in breastfeeding intention, initiation, or duration. Quality indicators were
      assessed and limitations reported. Effects were explored according to outcomes of
      intention, initiation, and duration. RESULTS: Fifteen papers were found to be
      eligible for the review. Having been breastfed as an infant was consistently
      correlated with breastfeeding intention, initiation, and duration. Effect sizes
      differed depending on methodology. Men's infant-feeding status was also related
      to later intentions to support or encourage a partner to breastfeed. CONCLUSIONS:
      Robust evidence for intergenerational breastfeeding continuity is present;
      however, mechanisms that explain this association were not considered in the
      studies reviewed and would best be explored within longitudinal cohort studies.

PMID- 25604645
TI  - Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in
      rats via regulation of toll-like receptor 4/nuclear factor-kappaB signaling
      pathway.
AB  - Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and
      cell apoptosis play a vital role, is frequently encountered in clinical practice.
      Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus,
      has been shown to confer protective effects against many cardiovascular diseases.
      The present study was aimed to investigate the antiinflammatory and antiapoptotic
      effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were
      randomly divided into sham operation group, MI/R group and groups with
      combinations of MI/R and different doses of AsIV. The results showed that the
      expressions of myocardial toll-like receptor 4 (TLR4) and nuclear factor-kappaB
      (NF-kappaB) were significantly increased, and apoptosis of cardiomyocytes was
      induced in MI/R group compared with that in sham operation group. Administration
      of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF
      kappaB and inhibited cell apoptosis as evidenced by decreased terminal
      deoxynucleotidyl transferase dUTP nick end labeling positive cells, B-cell
      lymphoma-2 associated X protein and caspase-3 expressions and increased B-cell
      lymphoma-2 expression compared with that in MI/R group. In addition, AsIV
      treatment reduced levels of inflammatory cytokines induced by MI/R injury. In
      conclusion, our results demonstrated that AsIV downregulates TLR4/NF-kappaB
      signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R
      injury in rats.

PMID- 25604646
TI  - Fine-tuning the nucleophilic reactivities of boron ate complexes derived from
      aryl and heteroaryl boronic esters.
AB  - Boron ate complexes derived from thienyl and furyl boronic esters and aryllithium
      compounds have been isolated and characterized by X-ray crystallography. Products
      and mechanisms of their reactions with carbenium and iminium ions have been
      analyzed. Kinetics of these reactions were monitored by UV/Vis spectroscopy, and
      the influence of the aryl substituents, the diol ligands (pinacol, ethylene
      glycol, neopentyl glycol, catechol), and the counterions on the nucleophilic
      reactivity of the boron ate complexes were examined. A Hammett correlation
      confirmed the polar nature of their reactions with benzhydrylium ions, and the
      correlation lg k(20  degrees C)=sN (E+N) was employed to determine the
      nucleophilicities of the boron ate complexes and to compare them with those of
      other borates and boronates. The neopentyl and ethylene glycol derivatives were
      found to be 10(4) times more reactive than the pinacol and catechol derivatives. 

PMID- 25604647
TI  - Changes in malaria epidemiology in a rural area of Cubal, Angola.
AB  - BACKGROUND: Scarce information about malaria epidemiology in Angola has been
      published. The objective of this study is to describe the epidemiology of malaria
      at the Hospital Nossa Senhora da Paz (Cubal, Angola) and the fatality rate due to
      malaria (total and in children under five years) in the last five years. METHODS:
      A retrospective, observational study was performed at the Hospital Nossa Senhora
      da Paz, a 400-bed rural hospital located in Benguela Province of Angola. The
      study population included all patients who attended the hospital from January
      2009 to December 2013. Outcome variables were calculated as follows: the
      percentage of malaria cases (number of positive thick blood films, divided by the
      total thick blood films performed); the percentage of in-patients for malaria
      (number of in-patients diagnosed with malaria, divided by the total number of in
      patients); and, the fatality rate (number of deaths due to malaria divided by the
      number of positive thick blood films). RESULTS: Overall, 23,106 thick blood films
      were performed, of which 3,279 (14.2%) were positive for Plasmodium falciparum
      infection. During this five-year period, a reduction of 40% (95% CI 37-43%, p <
      0.001) in the malaria-positive slides was detected. Distribution of positive
      malaria slides showed a seasonal distribution with a peak from December to March
      (rainy season). An average annual reduction of 52% (95% CI 50-54%, p < 0.001) in
      the admissions due to malaria was observed. The overall fatality rate due to
      malaria was 8.3%, and no significant differences in the annual fatality rate were
      found (p = 0.553). CONCLUSIONS: A reduction in the number of malaria cases and
      the number of admissions due to malaria has been observed at the Hospital Nossa
      Senhora da Paz, during the last five years, and incidence along the study period
      showed a seasonal distribution. All this information could be useful when
      deciding which malaria control strategies have to be implemented in this area.

PMID- 25604648
TI  - Contribution of the Interleukin-6/STAT-3 Signaling Pathway to Chondrogenic
      Differentiation of Human Mesenchymal Stem Cells.
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) are multipotent cells that can
      differentiate into chondrocytes. Articular cartilage contains MSC-like
      chondroprogenitor cells, which suggests their involvement in the maintenance of
      cartilage homeostasis by a self-repair mechanism. Interleukin-6 (IL-6) is a
      cytokine with a wide range of physiologic functions, which are produced by MSCs
      in a steady manner and in large quantities. The purpose of this study was to
      investigate the involvement of IL-6 signaling in MSC differentiation into
      chondrocytes. METHODS: Human bone marrow-derived MSCs were cultured using a
      pellet culture system in medium containing transforming growth factor beta3.
      Chondrogenic differentiation was detected by cartilage matrix accumulation and
      chondrogenic marker gene expression. RESULTS: IL-6 was detected at a high
      concentration in culture supernatants during chondrogenic differentiation. The
      expression of the IL-6 receptor (IL-6R) was significantly increased, accompanied
      by markedly increased phosphorylation and expression of STAT-3. Addition of IL-6
      and soluble IL-6R (sIL-6R) to the chondrogenic culture resulted in concentration
      dependent increases in cartilage matrix accumulation and cartilage marker gene
      expression (type II collagen/aggrecan/type X collagen). Phosphorylation of the
      master transcription factor SOX9 was enhanced upon addition of IL-6 and sIL-6R.
      STAT-3 knockdown suppressed chondrogenic differentiation. IL-6 and the MSC
      markers CD166 and nestin were colocalized in macroscopically normal human
      cartilage taken from the lateral femoral compartment of knees with medial
      tibiofemoral osteoarthritis. CONCLUSION: During differentiation of human MSCs
      into chondrocytes, the activation of IL-6/STAT-3 signaling positively regulated
      chondrogenic differentiation. The presence of IL-6 around MSC-like cells in the
      cartilage tissue was identified, suggesting that IL-6 contributes to homeostasis
      and cartilage self-repair by promoting chondrogenic differentiation.

PMID- 25604649
TI  - The anatomic variations of the posterior talofibular ligament associated with os
      trigonum and pathologies of related structures.
AB  - PURPOSE: The aim of this study is to investigate the detailed anatomy of the
      posterior talofibular ligament (PTFL) on MR images in patients with os trigonum.
      We also evaluated the pathological conditions of the PTFL, anterior talofibular
      ligament (ATFL), flexor hallucis longus (FHL) tendon, talus and os trigonum.
      METHODS: Ankle MRIs of 70 patients with os trigonum (study group) and 70 patients
      without it (control group) were reviewed for the anatomy of the anterior and
      posterior fibers of PTFL. The prevalence of PTFL and ATFL pathologies was also
      compared between two groups. Additionally FHL tenosynovitis and osseous
      pathologies were evaluated. RESULTS: The posterior fibers inserted into the
      lateral tubercule of the posterior process of the talus in the control group
      whereas if an os trigonum was present, the posterior fibers of PTFL were inserted
      only into the os trigonum. The origins of anterior and posterior fibers were the
      medial surface of the lateral malleolus and the insertion of the anterior fibers
      was lateral surface of the talus posterior to the lateral malleolar facet in both
      groups. There was a significant association between an abnormal PTFL, ATFL and
      the presence of os trigonum. FHL tenosynovitis was higher in the study group but
      it did not meet the statistical significance. The most common pathology of the
      talus and os trigonum was subchondral edema along the synchondrosis. CONCLUSIONS:
      In patients with os trigonum, the posterior fibers of the PTFL were inserted
      herein. In the case of an os trigonum signal alterations of ligaments were more
      common, which may reflect chronic instability.

PMID- 25604650
TI  - Questionnaire design: carry-over effects of overall acceptance question placement
      and pre-evaluation instructions on overall acceptance scores in central location
      tests.
AB  - Question placement and usage of pre-evaluation instructions (PEI) in
      questionnaires for food sensory analysis may bias consumers' scores via carry
      over effects. Data from consumer sensory panels previously conducted at a central
      location, spanning 11 years and covering a broad range of food product
      categories, were compiled. Overall acceptance (OA) question placement was studied
      with categories designated as first (the first evaluation question following
      demographic questions), after nongustation questions (immediately following
      questions that do not require panelists to taste the product), and later
      (following all other hedonic and just-about-right [JAR] questions, but
      occasionally before ranking, open-ended comments, and/or intent to purchase
      questions). Each panel was categorized as having or not having PEI in the
      questionnaire; PEI are instructions that appear immediately before the first
      evaluation question and show panelists all attributes they will evaluate before
      receiving test samples. Postpanel surveys were administered regarding the self
      reported effect of PEI on panelists' evaluation experience. OA scores were
      analyzed and compared (1) between OA question placement categories and (2)
      between panels with and without PEI. For most product categories, OA scores
      tended to be lower when asked later in the questionnaire, suggesting evidence of
      a carry-over effect. Usage of PEI increased OA scores by 0.10 of a 9-point
      hedonic scale point, which is not practically significant. Postpanel survey data
      showed that presence of PEI typically improved the panelists' experience. Using
      PEI does not appear to introduce a meaningful carry-over effect. 

PMID- 25604651
TI  - Renal cell carcinoma in young patients: a review of recent literature.
AB  - Renal cell carcinoma is most common in patients in the seventh decade of life.
      However, renal cell carcinoma (RCC) patients under the age of 40 represent 3-7%
      of all renal tumors. These young patients develop RCC from a variety of
      mechanisms including genetic syndromes, heritable mutations, and sporadic
      mutations. This population encompasses a distinct clinical entity that requires
      early identification and adjustments in standard practices including sometimes
      aggressive surgical measures in order to improve oncologic management.

PMID- 25604652
TI  - The future of research in female pelvic medicine.
AB  - Female pelvic medicine and reconstructive surgery (FPMRS) was recently recognized
      as a subspecialty by the American Board of Medical Specialties (ABMS). FPMRS
      treats female pelvic disorders (FPD) including pelvic organ prolapse (POP),
      urinary incontinence (UI), fecal incontinence (FI), lower urinary tract symptoms
      (LUTS), lower urinary tract infections (UTI), pelvic pain, and female sexual
      dysfunction (FSD). These conditions affect large numbers of individuals,
      resulting in significant patient, societal, medical, and financial burdens. Given
      that treatments utilize both medical and surgical approaches, areas of research
      in FPD necessarily cover a gamut of topics, ranging from mechanistically driven
      basic science research to randomized controlled trials. While basic science
      research is slow to impact clinical care, transformational changes in a field
      occur through basic investigations. On the other hand, clinical research yields
      incremental changes to clinical care. Basic research intends to change
      understanding whereas clinical research intends to change practice. However, the
      best approach is to incorporate both basic and clinical research into a
      translational program which makes new discoveries and effects positive changes to
      clinical practice. This review examines current research in FPD, with focus on
      translational potential, and ponders the future of FPD research. With a goal of
      improving the care and outcomes in patients with FPD, a strategic collaboration
      of stakeholders (patients, advocacy groups, physicians, researchers, professional
      medical associations, legislators, governmental biomedical research agencies,
      pharmaceutical companies, and medical device companies) is an absolute
      requirement in order to generate funding needed for FPD translational research. 

PMID- 25604654
TI  - Fast optical-resolution photoacoustic microscopy using a 2-axis water-proofing
      MEMS scanner.
AB  - Optical-resolution photoacoustic microscopy (OR-PAM) is a novel label-free
      microscopic imaging tool to provide in vivo optical absorbing contrasts.
      Specially, it is crucial to equip a real-time imaging capability without
      sacrificing high signal-to-noise ratios (SNRs) for identifying and tracking
      specific diseases in OR-PAM. Herein we demonstrate a 2-axis water-proofing MEMS
      scanner made of flexible PDMS. This flexible scanner results in a wide scanning
      range (9 * 4 mm(2) in a transverse plane) and a fast imaging speed (5 B-scan
      images per second). Further, the MEMS scanner is fabricated in a compact
      footprint with a size of 15 * 15 * 15 mm(3). More importantly, the scanning
      ability in water makes the MEMS scanner possible to confocally and simultaneously
      reflect both ultrasound and laser, and consequently we can maintain high SNRs.
      The lateral and axial resolutions of the OR-PAM system are 3.6 and 27.7 MUm,
      respectively. We have successfully monitored the flow of carbon particles in
      vitro with a volumetric display frame rate of 0.14 Hz. Finally, we have
      successfully obtained in vivo PA images of microvasculatures in a mouse ear. It
      is expected that our compact and fast OR-PAM system can be significantly useful
      in both preclinical and clinical applications. 

PMID- 25604653
TI  - Laboratory experiments on stranding of Anopheles larvae under different shoreline
      environmental conditions.
AB  - BACKGROUND: One of the concerns for future malaria epidemiology is the elevated
      risks of malaria around an ever-increasing number of dam sites. Controlling
      larval populations around reservoirs behind dams by manipulating the water levels
      of reservoirs could be an effective and sustainable measure for suppressing
      malaria epidemics; however, the effectiveness of the water-level manipulation and
      the contributing mechanisms have been poorly studied. In this paper, we focus on
      how water recession may lead to larval stranding. METHODS: Larvae of An.
      albimanus were studied to assess their susceptibility to stranding under
      different conditions representing reservoir shoreline environments in an
      experimental tank (50 cm * 100 cm). The tank was initially seeded with 80 larvae
      uniformly, and the numbers of larvae stranded on land and remaining in water were
      counted (summed up to recovered larvae), following the recession of water. The
      vertical water drawdown rate and the proportion of stranded larvae to recovered
      larvae (p) were measured. Shoreline conditions tested were inclinations of shore
      slopes (2% and 4%) and surface types (smooth, vegetated, rough, ridged). RESULTS:
      For the 2% slopes, the proportions of stranded larvae (p) increased by about
      0.002, 0.004, and 0.010 as the water drawdown rate increased by a centimeter per
      day on the smooth, rough, and vegetated surfaces, respectively. p for the 4%
      slopes were smaller than for the 2% slopes. Unlike other surface conditions, no
      significant correlation between p and the drawdown rate was observed on the
      ridged surface. CONCLUSIONS: Larger proportions of Anopheles larvae were stranded
      at higher water drawdown rates, on smaller reservoir slopes, and under rough or
      vegetated surface conditions. Three mechanisms of larval stranding were
      identified: falling behind shoreline recession; entrapment in small closed water
      bodies; and inhabitation in shallow areas. Depending on the local vectors of
      Anopheles mosquitoes, the conditions for their favorable breeding sites
      correspond to the conditions for large larval stranding. If these conditions are
      met, water-level manipulation could be an effective measure to control malaria
      along shorelines of reservoirs behind dams.

PMID- 25604657
TI  - Astragaloside IV ameliorates acute pancreatitis in rats by inhibiting the
      activation of nuclear factor-kappaB.
AB  - This study aimed to investigate the effects of astragaloside IV (AS-IV; 3-O-beta
      D-xylopyranosyl-6-O-beta-D-glucopyranosylcycloastragenol), which has been
      reported to have comprehensive pharmacological functions, on sodium taurocholate
      (NaTc)/L-arginine (L-Arg)-induced acute pancreatitis (AP) in rats in vivo and in
      rat pancreatic acinar cells in vitro. NaTc-induced experimental AP was induced in
      rats by injecting 4% NaTc (0.1 ml/100 g) in the retrograde direction of the
      biliopancreatic duct. L-Arg-induced experimental AP was induced in rats by 2
      intraperitoneal injections of 20% L-arg (3 g/kg), with an interval of 1 h between
      the injections. The rats were pre-treated AS-IV (50 mg/kg) or the vehicle (DMSO)
      2 h prior to the induction of AP. Enzyme-linked immunosorbent assay, H&E
      staining, myeloperoxidase (MPO) activity, reverse transcription-quantitative PCR,
      western blot analysis and immunohistochemistry were used to evaluate the effects
      of AS-IV on AP. The results revealed that treatment with AS-IV significantly
      reduced serum amylase and lipase levels, pancreatic pathological alterations, the
      secretion of pro-inflammatory cytokines, MPO activity, and the protein expression
      of nuclear factor-kappaB (NF-kappaB) in vivo. Moreover, pre-treatment with AS-IV
      significantly increased the expression levels of manganese superoxide dismutase
      and cuprum/zinc superoxide dismutase. In the in vitro experiment, treatment of
      the cells with AS-IV aslo reduced rat pancreatic acinar cell necrosis and nuclear
      NF-kappaB activity, and enhanced the protein expression of superoxide dismutase.
      In conclusion, this study indicates that the protective effects of AS-IV on
      experimental AP in rats may be closely related to the inhibition of NF-kappaB. In
      addition, our results indicate that AS-IV may exert potential antioxidant effects
      on AP. Therefore, AS-IV may be an effective therapeutic agent for AP.

PMID- 25604662
TI  - Whole-exome sequencing effective at diagnosing elusive genetic disorders: tests
      diagnose about 25% of patients, find a variety of mutation types.

PMID- 25604663
TI  - FDA proposes tighter regulation over genetic lab tests: federal agency cites need
      to improve test quality, minimize risk to patients.

PMID- 25604659
TI  - Obstructive sleep apnea in young infants with Down syndrome evaluated in a Down
      syndrome specialty clinic.
AB  - Children with Down syndrome (DS) experience congenital and functional medical
      issues that predispose them to obstructive sleep apnea (OSA). Research utilizing
      stringent age criteria among samples of infants with DS and OSA is limited. This
      study examines clinical correlates of OSA among infants with DS. A retrospective
      chart review was conducted of infants <=6 months of age referred to a DS clinic
      at a tertiary children's hospital over five-years (n = 177). Chi-square tests and
      binary logistic regression models were utilized to analyze the data. Fifty-nine
      infants underwent polysomnography, based on clinical concerns. Of these, 95%
      (56/59) had studies consistent with OSA. Among infants with OSA, 71% were
      identified as having severe OSA (40/56). The minimum overall prevalence of OSA
      among the larger group of infants was 31% (56/177). Significant relationships
      were found between OSA and dysphagia, congenital heart disease (CHD),
      prematurity, gastroesophageal reflux disease (GERD), and other functional and
      anatomic gastrointestinal (GI) conditions. Results indicate that odds of OSA in
      this group are higher among infants with GI conditions in comparison to those
      without. Co-occurring dysphagia and CHD predicted the occurrence of OSA in 36% of
      cases with an overall predictive accuracy rate of 71%. Obstructive sleep apnea is
      relatively common in young infants with DS and often severe. Medical factors
      including GI conditions, dysphagia and CHD may help to identify infants who are
      at greater risk and may warrant evaluation. Further studies are needed to assess
      the impact of OSA in infants with DS.

PMID- 25604665
TI  - Immunomodulatory properties and anti-apoptotic effects of zinc and melatonin in
      an experimental model of chronic Chagas disease.
AB  - The immunomodulatory effects of melatonin and zinc during chronic experimental
      Chagas' disease were studied. Early and late apoptosis by Annexin V-propidium
      iodide staining were evaluated. The expression of CD28, CD80, CD86, CD45RA and
      CD4(+)T and CD8(+)T cells were also evaluated by flow cytometry analysis. The
      combination of zinc and melatonin notably reduced the apoptotic ratios of splenic
      cells in the infected and treated animals when compared to untreated rats, during
      early and late stages of apoptosis. The percentages of CD8(+)T cells in Zn, Mel
      or Zn and Mel treated rats were reduced when compared to infected and untreated
      animals. Higher percentages of CD28 expression in CD4(+) and CD8(+) T cell
      populations were observed in control and infected Zn-treated group as compared to
      untreated ones. Zn, Mel or the combination of both did not induce any
      statistically significant differences for B cells when comparing to treated
      control and infected groups. Zinc or Mel-treated animals presented a lower
      expression of CD86 when compared to untreated counterparts. According to our
      data, this work strongly suggest that the modulation of the immune system
      operated by zinc and melatonin administration affected the balance among T cell
      immune response, apoptosis and expression of co-stimulatory molecules during
      chronic Trypanosoma cruzi infection, inducing important changes in the host's
      immune response against the parasite. Future experiments in this field should be
      focused in improving our understanding of the key mechanisms underlying the
      involvement of melatonin and zinc in the immune response during chronic Chagas'
      disease. 

PMID- 25604658
TI  - Characterization of human disease phenotypes associated with mutations in TREX1,
      RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.
AB  - Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations
      in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report
      on 374 patients from 299 families with mutations in these seven genes. Most
      patients conformed to one of two fairly stereotyped clinical profiles; either
      exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where
      data were available), or a post-natal presentation, usually within the first year
      of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a
      loss of previously acquired skills. Other clinically distinct phenotypes were
      also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and
      non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths
      (19.3% of patients with follow-up data). Of 285 patients for whom data were
      available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and
      intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy,
      intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic
      lupus erythematosus were seen frequently enough to be confirmed as real
      associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust
      relationship between mutations in all seven genes with increased type I
      interferon activity in cerebrospinal fluid and serum, and the increased
      expression of interferon-stimulated gene transcripts in peripheral blood. We
      recorded a positive correlation between the level of cerebrospinal fluid
      interferon activity assayed within one year of disease presentation and the
      degree of subsequent disability. Interferon-stimulated gene transcripts remained
      high in most patients, indicating an ongoing disease process. On the basis of
      substantial morbidity and mortality, our data highlight the urgent need to define
      coherent treatment strategies for the phenotypes associated with mutations in the
      Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a
      window of therapeutic opportunity exists relevant to the majority of affected
      patients and indicate that the assessment of type I interferon activity might
      serve as a useful biomarker in future clinical trials.

PMID- 25604667
TI  - Nanotherapeutic approach for opiate addiction using DARPP-32 gene silencing in an
      animal model of opiate addiction.
AB  - Opiates act on the dopaminergic system of the brain and perturb 32 kDa dopamine
      and adenosine 3', 5'-monophosphate-regulated phosphoprotein (DARPP-32) function.
      The DARPP-32 mediated inhibition of protein phosphatase-1 (PP-1) and modulation
      of transcriptional factor CREB is critical to the changes in neuronal plasticity
      that result in behavioral responses during drug abuse. To investigate the role of
      DARPP-32 mediated signaling on withdrawal behavior in a rat model of opiate
      addiction, we used intracerebral administration of gold nanorods (GNR) complexed
      to DARPP-32 siRNA to silence DARPP-32 gene expression and measure its effects on
      the opiate withdrawal syndrome. We hypothesized that DARPP-32 siRNA will suppress
      the neurochemical changes underlying the withdrawal syndrome and therefore
      prevent conditioned place aversion by suppressing or removing the constellation
      of negative effects associated with withdrawal, during the conditioning
      procedure. Our results showed that opiate addicted animals treated with GNR-DARPP
      32 siRNA nanoplex showed lack of condition place aversive behavior consequent to
      the downregulation of secondary effectors such as PP-1 and CREB which modify
      transcriptional gene regulation and consequently neuronal plasticity. Thus,
      nanotechnology based delivery systems could allow sustained knockdown of DARPP-32
      gene expression which could be developed into a therapeutic intervention for
      treating drug addiction by altering reward and motivational systems and interfere
      with conditioned responses.

PMID- 25604666
TI  - Mutations at tyrosine 88, lysine 92 and tyrosine 470 of human dopamine
      transporter result in an attenuation of HIV-1 Tat-induced inhibition of dopamine
      transport.
AB  - HIV-1 transactivator of transcription (Tat) protein disrupts the dopamine (DA)
      neurotransmission by inhibiting DA transporter (DAT) function, leading to
      increased neurocognitive impairment in HIV-1 infected individuals. Through
      integrated computational modeling and pharmacological studies, we have
      demonstrated that mutation of tyrosine470 (Y470H) of human DAT (hDAT) attenuates
      Tat-induced inhibition of DA uptake by changing the transporter conformational
      transitions. The present study examined the functional influences of other
      substitutions at tyrosine470 (Y470F and Y470A) and tyrosine88 (Y88F) and lysine92
      (K92M), two other relevant residues for Tat binding to hDAT, in Tat-induced
      inhibitory effects on DA transport. Y88F, K92M and Y470A attenuated Tat-induced
      inhibition of DA transport, implicating the functional relevance of these
      residues for Tat binding to hDAT. Compared to wild type hDAT, Y470A and K92M but
      not Y88F reduced the maximal velocity of [(3)H]DA uptake without changes in the
      Km. Y88F and K92M enhanced IC50 values for DA inhibition of [(3)H]DA uptake and
      [(3)H]WIN35,428 binding but decreased IC50 for cocaine and GBR12909 inhibition of
      [(3)H]DA uptake, suggesting that these residues are critical for substrate and
      these inhibitors. Y470F, Y470A, Y88F and K92M attenuated zinc-induced increase of
      [(3)H]WIN35,428 binding. Moreover, only Y470A and K92M enhanced DA efflux
      relative to wild type hDAT, suggesting mutations of these residues differentially
      modulate transporter conformational transitions. These results demonstrate Tyr88
      and Lys92 along with Tyr470 as functional recognition residues in hDAT for Tat
      induced inhibition of DA transport and provide mechanistic insights into
      identifying target residues on the DAT for Tat binding. 

PMID- 25604670
TI  - Treatment of head lice (Pediculus humanus capitis) infestation: is regular
      combing alone with a special detection comb effective at all levels?
AB  - Head lice infestation (HLI) caused by Pediculus humanus capitis has been a public
      health problem worldwide. Specially designed combs are used to identify head
      lice, while anti-lice products are applied on the scalp for treatment. In the
      present study, we aimed to test whether combing only by precision detection comb
      (PDC) or metal pin comb (MPC) could be effective alternatives to the use of anti
      lice products in children. A total of 560 children from two rural schools in
      Turkey were screened. In the PDC trial, children were combed every second day for
      14 days, while in the MPC trial, combing was performed once in every four days
      for 15 days. Children were divided into two groups (dry combing and wet combing)
      for both trials and results were compared. The results showed no significant
      differences between dry and wet combing strategies for both combs for the removal
      of head lice (p > 0.05). The number of adult head lice declined significantly on
      each subsequent combing day in both approaches, except on day 15 in the MPC
      trial. In the end, no louse was found in 54.1 and 48.9% of children in the PDC
      and MPC trials, respectively. Since family members of infested children were not
      available, they were not checked for HLI. Four times combing within 2 weeks with
      MPC combs was found effective for both treatment of low HLI and prevention of
      heavy HLI. In conclusion, regular combing by special combs decreases HLI level in
      children and is safely applicable as long-term treatment.

PMID- 25604668
TI  - Achieving International Society for Pediatric and Adolescent Diabetes and
      American Diabetes Association clinical guidelines offers cardiorenal protection
      for youth with type 1 diabetes.
AB  - OBJECTIVE: Most youth with type 1 diabetes do not meet the American Diabetes
      Association (ADA) and International Society for Pediatric and Adolescent Diabetes
      (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body
      mass index (BMI). We hypothesized that ISPAD/ADA goal achievement at baseline
      would be associated with cardiorenal risk factors at baseline and 2 yr follow-up
      in adolescents with type 1 diabetes. METHODS: We assessed the cross-sectional and
      longitudinal relationships between ISPAD/ADA goal achievement at baseline and
      cardiorenal health at baseline and 2-yr follow-up (n = 297; 15.4 +/- 2.1 yr at
      baseline) in adolescents with type 1 diabetes. Goal achievement was defined as
      HbA1c < 7.5%, BP < 90th percentile for age, sex, and height, low density
      lipoprotein-cholesterol (LDL-C) <100 mg/dL, high density lipoprotein-cholesterol
      (HDL-C) >35 mg/dL, triglycerides (TG) <150 mg/dL and BMI <85th percentile for age
      and sex. Cardiorenal outcomes included pulse-wave velocity (PWV), brachial
      distensibility (BrachD), augmentation index (AIx), and epidermal growth factor
      receptor (eGFR) continuously and categorically as hyperfiltration (eGFR >= 135
      mL/min/1.73 m(2)). RESULTS: Adolescents with type 1 diabetes who met 1-3 goals,
      had significantly greater (P < 0.05) baseline PWV (5.1 +/- 0.1 vs. 5.4 +/- 0.1
      m/s), follow-up PWV (5.5 +/- 0.1 vs. 5.7 +/- 0.1 m/s), greater follow-up eGFR
      (104 +/- 2 vs. 116 +/- 3 mL/min/1.73 m(2)), and greater odds of renal
      hyperfiltration at follow-up (odds ratio (OR): 20.0, 95% confidence interval
      (CI): 3.8-105.2) compared to those who met 4-6 goals after adjusting for Tanner
      stage, sex, age, and diabetes duration. No statistically significant differences
      in the cardiorenal outcomes were observed between adolescents with type 1
      diabetes who met 4-6 goals and non-diabetic controls (n = 96). CONCLUSIONS: In
      adolescents with type 1 diabetes, baseline ADA/ISPAD goal achievement was
      associated with cardiorenal protection at baseline and 2-yr follow-up.

PMID- 25604671
TI  - Lethal activity of individual and mixed monoterpenoids of geranium essential oil
      on Musca domestica.
AB  - Plant essential oils and its constituent molecules have been suggested as an
      alternative to control insect. The contribution of the constituents to the effect
      of the oil is determined by the interactions occurring between them. Synergistic
      interactions would improve the insecticide efficacy of the compounds due to the
      utilization of lower doses. We evaluated the insecticidal activity of geranium
      (Geranium maculatum L.) oil and its major constituents against Musca domestica L.
      and studied the toxic interactions in artificial mixtures of those constituents
      in the natural ratio. While synergistic interactions were determined in house fly
      in this study, these were of low intensity evidencing that the effect of each
      constituent was slightly modified by the other constituents present in the
      mixtures. The search for synergism between components is a strategy to improve
      the insecticide activity of natural compounds. The synergism helps to reduce the
      environmental and toxicological impact due to the reduction of the dose of use. 

PMID- 25604672
TI  - Protective immunity against Naegleria fowleri infection on mice immunized with
      the rNfa1 protein using mucosal adjuvants.
AB  - The free-living amoeba, Naegleria fowleri, causes a fatal disease called primary
      amoebic meningoencephalitis (PAM) in humans and experimental animals. Of the
      pathogenic mechanism of N. fowleri concerning host tissue invasion, the adherence
      of amoeba to hose cells is the most important. We previously cloned the nfa1 gene
      from N. fowleri. The protein displayed immunolocalization in the pseudopodia,
      especially the food-cups structure, and was related to the contact-dependent
      mechanism of the amoebic pathogenicity in N. fowleri infection. The cholera toxin
      B subunit (CTB) and Escherichia coli heat-labile enterotoxin B subunit (LTB) have
      been used as potent mucosal adjuvants via the parenteral route of immunization in
      most cases. In this study, to examine the effect of protective immunity of the
      Nfa1 protein for N. fowleri infection with enhancement by CTB or LTB adjuvants,
      intranasally immunized BALB/c mice were infected with N. fowleri trophozoites for
      the development of PAM. The mean time to death of mice immunized with the Nfa1
      protein using LTB or CTB adjuvant was prolonged by 5 or 8 days in comparison with
      that of the control mice. In particular, the survival rate of mice immunized with
      Nfa1 plus CTB was 100% during the experimental period. The serum IgG levels were
      significantly increased in mice immunized with Nfa1 protein plus CTB or LTB
      adjuvants. These results suggest that the Nfa1 protein, with CTB or LTB
      adjuvants, induces strong protective immunity in mice with PAM due to N. fowleri
      infection.

PMID- 25604673
TI  - Genotypic characterization of amoeba isolated from Acanthamoeba keratitis in
      Poland.
AB  - Free-living amoebae belonging to the genus Acanthamoeba are the causative factor
      of many diseases. Among others, they cause Acanthamoeba keratitis (AK), a
      condition that usually occurs in contact lens wearers, though it is also observed
      in non-wearers. The number of diagnosed cases of AK increased more than eightfold
      during 8 years in the USA, and a proportional increase in frequency also occurred
      in Poland and Europe. Cases of AK are usually diagnosed late, and their therapy
      is difficult and rarely successful. AK is an uncommon diagnosis in Poland. The
      increased number of positive cases observed in our laboratory may reflect the
      growing at-risk population of contact lens wearers. Acanthamoeba as a genus of
      facultative human parasites is currently classified into 17 genotypes. Isolates
      belonging to seven genotypes were found to be associated with AK. One genotype in
      particular, T4, was found to be overrepresented in human disease. The main
      finding of our study is that in Poland, AK is almost always associated with the
      T4 genotype.

PMID- 25604674
TI  - Ultrasound-assisted aqueous two-phase extraction of phenylethanoid glycosides
      from Cistanche deserticola Y. C. Ma stems.
AB  - An efficient ultrasound-assisted aqueous two-phase extraction and enrichment
      process for phenylethanoid glycosides from Cistanche deserticola Y. C. Ma stems
      was developed in this work. An ethanol/ammonium sulfate system was chosen for the
      aqueous two-phase system due to its fine partitioning and recycling behaviors.
      Single-factor experiments and response surface methodology were used to optimize
      the process parameters of the ultrasound-assisted aqueous two-phase extraction.
      The optimal conditions were as follows: a salt concentration of 23.5%, an ethanol
      concentration of 20%, an extraction time of 37 min, an extraction temperature of
      30 degrees C, a liquid/solid ratio of 30:1 w/w, and an ultrasound power of 300 W.
      Under the above conditions, the extraction yields of echinacoside and acteoside
      (the main components of phenylethanoid glycosides) reached 5.35 and 6.22 mg/g dry
      material weight, respectively. The contents of echinacoside and acteoside in the
      extracts reached 27.56 and 30.23 mg/g, respectively, which were 2.46- and 2.58
      fold higher than the amounts obtained in ultrasound-assisted extraction. In
      conclusion, ultrasound-assisted aqueous two-phase extraction was an efficient,
      ecofriendly, and economical method, and it may be a promising technique for
      extracting and enriching bioactive components from plants. 

PMID- 25604675
TI  - Aqueous humor concentration of VEGF and retinal oxygen saturation after
      unilateral acute primary angle closure.
AB  - PURPOSE: To measure the levels of vascular endothelial growth factor (VEGF) in
      aqueous humor in patients with unilateral acute primary angle closure (APAC) and
      retinal oxygen saturation (SO2 ) after trabeculectomy. METHODS: Twelve patients,
      with unilateral trabeculectomy-required APAC, were recruited as the study group.
      Aqueous humor samples were collected prospectively for every subject. VEGF
      concentrations were analysed via enzyme-linked immunosorbent assay (ELISA), and
      retinal SO2 was measured using oximeter (Reykjavik, Iceland) at 1 month after
      trabeculectomy. RESULTS: In the APAC eyes, the mean aqueous humor concentration
      of VEGF was 388.4 +/- 260.1 pg/ml and positively correlated with preoperative
      intraocular pressure (rho = 0.658, p = 0.020). In the normal controls, the mean
      SO2 levels in the larger arterioles and venules were 93.0 +/- 5.9% and 59.5 +/-
      5.4% and the arteriovenous [A-V] difference was 33.5 +/- 6.3%. In the study
      group, the arteriolar SO2 at 1 month after surgery (97.6 +/- 19.4%, p = 0.147)
      did not differ significantly from the values in the control group. However, the
      mean venular SO2 was significantly lower than the control eyes (50.0 +/- 9.1%
      versus 59.5 +/- 5.4%, p = 0.004), and a remarkable increased A-V difference (47.6
      +/- 22.7% versus 33.5 +/- 6.3%) was found in the APAC eyes (p = 0.037).
      CONCLUSIONS: Lower venular SO2 and increased A-V difference existed in the APAC
      eyes after surgery, and it is possible that the saturation was even lower during
      the attack. Together with the elevated VEGF concentrations in aqueous humor,
      these provided indirect evidence that ocular hypoxia was constantly present
      during APAC attack.

PMID- 25604676
TI  - [Retrospective computation of the ISS in multiple trauma patients: Potential
      pitfalls and limitations of findings in full body CT scans].
AB  - INTRODUCTION: The Injury Severity Score (ISS) is a well-established anatomical
      scoring system for polytraumatized patients. However, any inaccuracy in the
      Abbreviated Injury Score (AIS) directly increases the ISS impreciseness. Using
      the full body computed tomography (CT) scan report, ISS computation can be
      associated with certain pitfalls. This study evaluates interpretation variations
      depending on radiological reports and indicates requirements to reliably
      determine the ISS. MATERIALS AND METHODS: The ISS of 81 polytraumatized patients
      was calculated based on the full body CT scan report. If an injury could not be
      attributed to a precise AIS cipher, the minimal and maximal ISS was computed.
      Real ISS included all conducted investigations, intraoperative findings, and
      final medical reports. The differences in ISS min, ISS max, and ISS real were
      evaluated using the Kruskal-Wallis test (p<0.05) and plotted in a linear
      regression analysis. RESULTS: Mean ISS min was 24.0 (+/- 0.7 SEM) points, mean
      ISS real 38.6 (+/-1.3 SEM) and mean ISS max was 48.3 (+/-1.4 SEM) points. All
      means were significantly different compared to one another (p<0.001). The
      difference between possible and real ISS showed a distinctive variation. Mean
      deviation was 9.7 (+/-0.9 SEM) points downward and 14.5 (+/-1.1 SEM) points
      upward. The difference between deviation to ISS min and ISS max was highly
      significant (p<0.001). CONCLUSION: Objectification of injury severity in
      polytraumatized patients using the ISS is an internationally well-established
      method in clinical and scientific settings. The full body CT scan report must
      meet distinct criteria and has to be written in acquaintance to the AIS scale if
      intended to be used for correct ISS computation.

PMID- 25604677
TI  - [Percutaneous stabilization of traumatic spondylolisthesis in a child].
AB  - A 12-year-old boy suffered a rare occurrence of a traumatic spondylolisthesis
      (L5/S1) without neurological alterations after being partially buried underneath
      a collapsing brick wall. Additionally he sustained a third degree open fracture
      of the left distal fibula and epiphysiolysis of the left distal tibia. A closed
      reduction and percutanous dorsal instrumentation L5/S1 as well as an open
      reduction and osteosynthesis of the tibia and fibula were performed. After 6
      months the instrumentation was completely removed and an unrestrained range of
      motion of the lumbar spine and the upper ankle joint was regained. 

PMID- 25604678
TI  - Epidemiology of Theileria bicornis among black and white rhinoceros
      metapopulation in Kenya.
AB  - BACKGROUND: A huge effort in rhinoceros conservation has focused on poaching and
      habitat loss as factors leading to the dramatic declines in the endangered
      eastern black rhinoceros (Diceros bicornis michaeli) and the southern white
      rhinoceros (Ceratotherium simum simum). Nevertheless, the role disease and
      parasite infections play in the mortality of protected populations has largely
      received limited attention. Infections with piroplasmosis caused by Babesia
      bicornis and Theileria bicornis has been shown to be fatal especially in small
      and isolated populations in Tanzania and South Africa. However, the occurrence
      and epidemiology of these parasites in Kenyan rhinoceros is not known. RESULTS:
      Utilizing 18S rRNA gene as genetic marker to detect rhinoceros infection with
      Babesia and Theileria, we examined blood samples collected from seven rhinoceros
      populations consisting of 114 individuals of black and white rhinoceros. The goal
      was to determine the prevalence in Kenyan populations, and to assess the
      association of Babesia and Theileria infection with host species, age, sex,
      location, season and population mix (only black rhinoceros comparing to black and
      white rhinoceros populations). We did not detect any infection with Babesia in
      the sequenced samples, while the prevalence of T. bicornis in the Kenyan
      rhinoceros population was 49.12% (56/114). White rhinoceros had significantly
      higher prevalence of infection (66%) compared to black rhinoceros (43%). The
      infection of rhinoceros with Theileria was not associated with animal age, sex or
      location. The risk of infection with Theileria was not higher in mixed species
      populations compared to populations of pure black rhinoceros. CONCLUSION: In the
      rhinoceros studied, we did not detect the presence of Babesia bicornis, while
      Theileria bicornis was found to have a 49.12% prevalence with white rhinoceros
      showing a higher prevalence (66%) comparing with black rhinoceros (43%). Other
      factors such as age, sex, location, and population mix were not found to play a
      significant role.

PMID- 25604679
TI  - Sweat pore mapping using a fluorescein-polymer composite film for fingerprint
      analysis.
AB  - A simple but efficient sweat pore mapping method based on a fluorescein-PVP
      composite film was developed for fingerprint analysis. The composite film
      displays a fluorometric turn-on response upon contact with a small quantity of
      water secreted from human sweat pores, allowing precise mapping of sweat pores on
      a fingertip. 

PMID- 25604680
TI  - The Autonomic System Functional State Predicts Responsiveness in Disorder of
      Consciousness.
AB  - Diagnosis and early prognosis of the vegetative state/unresponsive wakefulness
      syndrome (VS/UWS) and its differentiation from the minimally-conscious state
      still rest on the clinical observation of responsiveness. The incidence of
      established clinical indicators of responsiveness also has proven variable in the
      single subject and is correlated to measures of heart rate variability (HRV)
      describing the sympathetic/parasympathetic balance. We tested responsiveness when
      the HRV descriptors nuLF and peakLF were or were not in the ranges with highest
      incidence of response based on findings from previous studies (10.0-70.0 and 0.05
      0.11 Hz, respectively). Testing was blind by The Coma Recovery Scale-revised in
      the two conditions and in two experimental sessions with a one-week interval. The
      incidence of responses was not randomly distributed in the "response" and "no
      response" conditions (McNemar test; p < 0.0001). The observed incidence in the
      "response" condition (visual: 55.1%; auditory: 51.5%) was higher than predicted
      statistically (32.1%) or described in previous clinical studies; responses were
      only occasional in the "no-response" condition (visual, 15.9%; auditory, 13.4%).
      Models validated the predictability with high accuracy. The current clinical
      criteria for diagnosis and prognosis based on neurological signs should be
      reconsidered, including variability over time and the autonomic system functional
      state, which could also qualify per se as an independent indicator for diagnosis
      and prognosis.

PMID- 25604681
TI  - Temporal summation in children with a history of retinopathy of prematurity.
AB  - PURPOSE: To assess temporal summation in children with a history of retinopathy
      of prematurity (ROP) by determining the critical duration (tCRIT) for complete
      temporal summation under rod-mediated conditions. From prior ERG studies, it is
      known that the kinetics of activation of phototransduction are prolonged in the
      ROP rod photoreceptor. METHODS: Dark-adapted thresholds for detecting 10 degrees 
      diameter stimuli with durations from 10 to 640 ms were measured. A two
      alternative, spatial, forced-choice psychophysical procedure was used. The tCRIT
      for complete summation was estimated in former preterm subjects with a history of
      severe ROP (n = 7), mild ROP (n = 23), and no ROP (n = 15). The subjects ranged
      in age from 10.4 to 17.6 (median 15.6) years. Age-similar term-born control
      subjects (n = 5) were also tested. RESULTS: Critical duration was significantly
      longer in subjects with a history of ROP than in subjects who never had ROP or
      who were born at term. Mean tCRIT in the mild ROP group [127.5 (SD = 19.9) ms]
      and severe group [147.6 (SD = 18.9) ms] did not differ significantly, but both
      were significantly longer than in former preterms who never had ROP [101.1 (SD =
      16.5) ms] and in term-born controls [101.0 (SD = 19.5) ms]. CONCLUSIONS: In ROP
      subjects, tCRIT is significantly prolonged. This is likely due to abnormal
      kinetics in the rod outer segment.

PMID- 25604682
TI  - Unaltered retinal dopamine levels in a C57BL/6 mouse model of form-deprivation
      myopia.
AB  - PURPOSE: Retinal dopamine has been long implicated in the signaling pathway
      regulating eye growth, as evidenced by its reduced levels in myopic eyes in
      various species. We examined whether and how retinal dopamine levels were changed
      in a C57BL/6 mouse model of experimental myopia. METHODS: Form-deprivation myopia
      (FDM) was induced in C57BL/6 mice by wearing monocular occluder for 4 weeks.
      Refractive errors were measured using an infrared photorefractor. Retinal
      dopamine/DOPAC and vitreal DOPAC levels were assessed by high-performance liquid
      chromatography (HPLC). Extracellular dopamine concentrations were examined by
      Western blot analysis of dopamine transporter (DAT) expression levels. The
      intactness of retinal dopaminergic system was evaluated by counting tyrosine
      hydroxylase (TH) immunoreactive cells, measuring the areas occupied by processes
      of these cells, and quantifying retinal TH expression at both protein and
      transcription levels. RESULTS: Form-deprivation myopia was successfully induced
      in C57BL/6 mice with the refractive status of deprived eyes being significantly
      different from fellow eyes. Unlike most of the previous results obtained in other
      myopic animal models, however, no significant changes in retinal dopamine, DOPAC,
      DAT, and vitreal DOPAC levels were detected in deprived eyes, either in the
      daytime or at night. Furthermore, neither the number of dopaminergic amacrine
      cells, the area size occupied by the processes of these cells, nor retinal TH
      expression, were altered in deprived eyes. CONCLUSIONS: The retinal dopamine
      system remains intact in C57BL/6 mice with FDM, and retinal dopamine levels are
      not associated with the development of FDM in this mouse strain.

PMID- 25604683
TI  - A low-molecular-weight oil cleaner for removal of leftover silicone oil
      intraocular tamponade.
AB  - PURPOSE: Silicone oil (SO) has been used as a long-term intraocular tamponade in
      treating retinal diseases for more than half a decade. However, its propensity to
      form tiny SO droplets is associated with a number of complications. Currently
      there is no effective way to remove such droplets from the eye cavity. In this
      work, a novel cleaner was developed for effective removal of these droplets.
      METHODS: The cleaner promotes the formation of an oil-in-water-in-oil (O/W/O)
      double-emulsion that consists of the unwanted droplets as the innermost oil
      phase. The cleaner's ability to encapsulate SO droplets was tested using both in
      vitro microdevices and ex vivo porcine eye models. The efficiency of the cleaner
      in removing the SO droplets was quantified using the three-dimensional (3D)
      printed eye model. Both the volatility and in vitro cytotoxicity of the cleaner
      were evaluated on three retinal cell lines. RESULTS: Cleaner 1.0 is volatile and
      has an evaporation rate of 0.14 mL/h at room temperature. The formation of O/W/O
      double-emulsion indicates the encapsulation of SO droplets by the cleaner. In the
      3D printed eye model, rinsing with cleaner 1.0 led to a significant reduction of
      leftover SO droplets compared with 1* phosphate-buffered saline (PBS; P < 0.05; n
      = 6). Cleaner 1.0 did not cause significant cell death (3%-6%) compared with
      balance salt solution (BSS; 1%-3%) in all three cell lines. The reduction in the
      cell viability due to cleaner 1.0, relative to that of BSS, was significant only
      in ARPE-19 cells (27%; P < 0.05) but not in the other two cell lines (8% and 17%,
      respectively; P > 0.05). CONCLUSIONS: The double-emulsification approach was
      effective in removing remnant droplets from the eye cavities, and the cleaner was
      compatible with common cell types encountered in human eyes. The mechanism of
      toxicity of the proposed cleaner is still unknown, therefore, further in vivo
      animal tests are needed for full evaluation of the physiological response before
      the proposed cleaner can be advanced to clinical trials for retinal surgeries.

PMID- 25604685
TI  - Inhibition of T-cell activation by retinal pigment epithelial cells derived from
      induced pluripotent stem cells.
AB  - PURPOSE: The purpose of this study was to determine whether human retinal pigment
      epithelial (RPE) cells from induced pluripotent stem (iPS) cells could inhibit T
      cell activation in vitro. METHODS: Cultured iPS-derived RPE (iPS-RPE) cells were
      established from fresh skin tissues or dental pulp cells obtained from healthy
      donors or a retinal patient after informed consent was obtained. To confirm
      expression of the specific markers on iPS and iPS-RPE cells,
      immunohistochemistry, quantitative RT-PCR (qRT-PCR), and flow cytometry were
      performed. Target T cells were obtained from peripheral blood mononuclear cells
      of healthy donors. Target T cells were assessed for proliferation by
      incorporation of bromodeoxyuridine or carboxyfluorescein succinimidyl ester for
      production of cytokines such as IFN-gamma. Expression of TGFbeta and other
      candidate molecules by iPS-RPE cells was evaluated with flow cytometry, ELISA,
      multiplex cytokine array, immunohistochemistry, and qRT-PCR. RESULTS: The RPE
      cells we established from iPS cells had many characteristics of mature RPE cells
      but no characteristics of pluripotent stem cells. Cultured iPS-RPE cells
      inhibited cell proliferation and production of IFN-gamma by activated CD4(+) T
      cells. In some bystander T cells, iPS-derived RPE cells induced CD25(+)Foxp3(+)
      regulatory T cells in vitro. Induced pluripotent stem-RPE cells constitutively
      expressed TGFbeta and suppressed activation of T cells via soluble TGFbeta,
      because TGFbeta-downregulated iPS-RPE cells did not inhibit this T-cell
      activation. CONCLUSIONS: Cultured iPS-derived retinal cells fully suppress T-cell
      activation. Transplantation of iPS-RPE cells into the eye might be a therapy for
      retinal disorders.

PMID- 25604684
TI  - Evaluation of a Method for Estimating Retinal Ganglion Cell Counts Using Visual
      Fields and Optical Coherence Tomography.
AB  - PURPOSE: To evaluate the accuracy and generalizability of a published model that
      derives estimates of retinal ganglion cell (RGC) counts and relates structural
      and functional changes due to glaucoma. METHODS: Both the Harwerth et al.
      nonlinear model (H-NLM) and the Hood and Kardon linear model (HK-LM) were applied
      to an independent dataset of frequency-domain optical coherence tomography and
      visual fields, consisting of 48 eyes of 48 healthy controls, 100 eyes of 77
      glaucoma patients and suspects, and 18 eyes of 14 nonarteritic anterior ischemic
      optic neuropathy (ION) patients with severe vision loss. Using the coefficient of
      determination R2, the models were compared while keeping constant the topographic
      maps, specifically a map by Garway-Heath et al. and a separate map by Harwerth et
      al., which relate sensitivity test stimulus locations to corresponding regions
      around the optic disc. Additionally, simulations were used to evaluate the
      assumptions of the H-NLM. RESULTS: Although the predictions of the HK-LM with the
      anatomically-derived Garway-Heath et al. map were reasonably good (R2 = 0.31
      0.64), the predictions of the H-NLM were poor (R2 < 0) regardless of the map
      used. Furthermore, simulations of the H-NLM yielded results that differed
      substantially from RGC estimates based on histology from human subjects. Finally,
      the value-added of factors increasing the relative complexity of the H-NLM, such
      as assumptions regarding age- and stage-dependent corrections to structural
      measures, was unclear. CONCLUSIONS: Several of the assumptions underlying the H
      NLM should be revisited. Studies and models relying on the RGC estimates of the H
      NLM should be interpreted with caution.

PMID- 25604686
TI  - Canonical/beta-catenin Wnt pathway activation improves retinal pigmented
      epithelium derivation from human embryonic stem cells.
AB  - PURPOSE: The purpose of this study was to better understand the role
      canonical/beta-catenin Wnt signaling plays in the differentiation of human
      embryonic stem cells (hESCs) into retinal pigmented epithelium (RPE), with the
      goal of improving methods for derivation. METHODS: Fluorescent reporters were
      generated to monitor RPE differentiating from hESCs by using a previously
      described 14-day derivation protocol. Reporters were used to test the effects of
      the canonical/beta-catenin Wnt pathway agonist CHIR99021 on differentiating RPE.
      Cells derived from differentiation studies were characterized by lineage-specific
      transcription factor expression, morphology, pigmentation, and function. The RPE
      derivation efficiency was determined from percentage positive PMEL17 expression.
      RESULTS: Fluorescent reporters mimicked expression of endogenous genes during 14
      day differentiation to RPE. Analysis of Wnt pathway gene expression showed that
      the pathway components are expressed in differentiating RPE cells. Addition of
      CHIR99021 improved RPE derivation based on morphology, expression of RPE-specific
      lineage markers, and genes involved in melanogenesis. Additionally, expression of
      the neural retina marker CHX10 was suppressed during differentiation with
      CHIR99021. Addition of soluble WNT3A, but not WNT5A, had the same result. The
      CHIR99021-modified protocol yielded cell populations that were 97.77% +/- 0.1%
      positive for the RPE marker PMEL17 at day 14. After cells were expanded to
      passage 3, they were shown to express RPE markers, carry out phagocytosis of rod
      outer segments, and secrete pigment epithelium-derived factor apically and
      vascular endothelial growth factor basally. CONCLUSIONS: Our findings
      demonstrated the importance of canonical/beta-catenin Wnt signaling in RPE
      differentiation and showed that manipulating the pathway significantly improves
      RPE derivation from hESC.

PMID- 25604687
TI  - Microarray analysis of gene expression in fibrovascular membranes excised from
      patients with proliferative diabetic retinopathy.
AB  - PURPOSE: We determined the profile of genes expressed in fibrovascular membranes
      (FVMs). METHODS: Six FVMs were surgically removed from patients with
      proliferative diabetic retinopathy (PDR) during pars plana vitrectomy with
      membrane peeling. The FVMs were classified into three active FVMs or three
      inactive FVMs according to the presence or absence of neovascularization (NV) in
      the membranes. Total RNA was isolated from the six FVMs and also from three
      normal human retinas. The DNA microarray analysis was performed to compare the
      genes expressed in the FVMs to those in normal human retinas, and also between
      active and inactive FVMs. Ingenuity pathway analysis (IPA) was used to determine
      the key biological networks related to the genes that were significantly altered.
      Quantitative RT-PCR and immunohistochemistry were performed to validate the
      microarray analyses. RESULTS: There were 87 genes expressed at significantly
      higher levels in FVMs than in normal human retinas. Functional classification of
      these genes showed that the most clustered genes were those related to
      extracellular matrix formation. The top biological network generated by the IPA
      was cellular assembly and organization involving nodes of genes related to
      extracellular matrix formation. These networks included the collagen family and
      matricellular proteins, THBS2, POSTN, and TNC. There were 91 genes significantly
      upregulated in active FVMs, and the most clustered functional category was
      angiogenesis. In contrast, 89 genes were significantly upregulated in inactive
      FVMs, and the most clustered functional category was metabolism. The IPA revealed
      that the top biological network related to the genes that were significantly
      altered in this comparison was cell-to-cell signaling, and interactions involving
      the PDGF and TGFbeta families. The results of quantitative RT-PCR analyses and
      immunohistochemistry for several selected molecules were in good agreement with
      the microarray data. CONCLUSIONS: Our data indicate that extracellular matrix
      related molecules such as POSTN, TNC, TGFbeta, and angiogenic factors have
      important roles in promoting the development of FVMs associated with PDR.

PMID- 25604688
TI  - Cyclocoagulation of the ciliary bodies by high-intensity focused ultrasound: a 12
      month multicenter study.
AB  - PURPOSE: To evaluate the safety and efficacy of high-intensity focused ultrasound
      (HIFU) cyclocoagulation in reducing intraocular pressure (IOP) in patients with
      refractory glaucoma by using a novel miniaturized delivery device (EyeOP1).
      METHODS: We conducted a 12-month open-label multicenter prospective study
      (EyeMUST1 Study). Patients with primary (primary open-angle glaucoma [POAG]) or
      secondary refractory glaucoma were treated in two groups depending on the
      duration of each ultrasound shot (group 1: 4 seconds; group 2: 6 seconds). The
      primary efficacy outcome was based on IOP reduction at 6 and 12 months. RESULTS:
      Fifty-two patients were enrolled: 36 (69%) had POAG and 16 (31%) had secondary
      glaucoma. Group 1 (n = 24) and group 2 (n = 28) had similar demographics and
      baseline characteristics. In group 1, IOP was reduced from a mean preoperative
      value of 29.7 +/- 7.7 mm Hg (n = 3.5 glaucoma medications) to a mean
      postoperative value of 21.3 +/- 6.7 mm Hg (n = 3.5 glaucoma medications) and 20.1
      +/- 6.7 mm Hg (n = 3.2 glaucoma medications) at 6 and 12 months, respectively. In
      group 2, IOP was reduced from a mean preoperative value of 29.0 +/- 7.4 mm Hg (n
      = 3.3 glaucoma medications) to a mean postoperative value of 20.2 +/- 7.4 mm Hg
      (n = 3.4 glaucoma medications) and 18.5 +/- 6.6 mm Hg (n = 3.5 glaucoma
      medications) at 6 and 12 months, respectively. At 12 months, the IOP reduction
      was sustained in both groups (32% IOP reduction in group 1 and 36% IOP reduction
      in group 2). The overall tolerance of the technique was good, with no serious
      adverse events. CONCLUSIONS: The new miniaturized HIFU EyeOP1 delivery device
      seems to be effective in decreasing IOP in patients with refractory glaucoma. The
      technology offers a good safety profile. (ClinicalTrials.gov number,
      NCT01338467.).

PMID- 25604689
TI  - Subfoveal choroidal thickness and cataract: the Beijing Eye Study 2011.
AB  - PURPOSE: This study examined subfoveal choroidal thickness (SFCT) in eyes with
      cataracts. METHODS: The population-based Beijing Eye Study 2011 included 3468
      individuals with a mean age of 64.6 +/- 9.8 years (range, 50-93 years of age).
      Enhanced depth imaging spectral domain optical coherence tomography was applied
      for measurement of SFCT. Using lens photographs, we graded cataracts by the Age
      Related Eye Disease Study system. RESULTS: Assessments of SFCT and cataract were
      available for 2548 subjects. After adjusting for age, axial length, sex, anterior
      chamber depth, and lens thickness, we found that SFCT was not significantly
      associated with presence of nuclear cataract (P = 0.41). Conversely, the degree
      of nuclear cataract (P = 0.73) was not significantly associated with SFCT after
      adjusting for age and sex. In contrast, thicker SFCT was significantly associated
      with lower degree of posterior subcapsular cataract (P = 0.027; standardized
      regression coefficient beta: -0.04; regression coefficient B: -127; 95%
      confidence interval [CI]: -240 to -15) or with lower degree of cortical cataract
      (P = 0.028; beta:-0.06; B: -51.5; 95% CI: -97.3 to -5.59) after adjusting for
      younger age, shorter axial length, and deeper anterior chamber. Conversely, the
      degree of posterior subcapsular cataract (P = 0.027; beta:-0.06) or the degree of
      cortical cataract (P = 0.01; beta: -2.55) was associated with thinner SFCT in
      multivariate analysis. Correspondingly in binary regression analysis, presence of
      subcapsular cataract was associated with older age (P < 0.001; odds ratio (OR):
      1.11; 95% CI: 1.09-1.14) and thinner SFCT (P = 0.006; OR: 0.997; 95% CI: 0.995
      0.999). CONCLUSIONS: Although nuclear cataract was not significantly associated
      with an abnormal SFCT, the association between thin SFCT and subcapsular cataract
      or cortical cataract may have clinical importance, because thin SFCT is
      associated with low vision.

PMID- 25604690
TI  - Major depressive and anxiety disorders in visually impaired older adults.
AB  - PURPOSE: We assessed the prevalence of subthreshold depression and anxiety, and
      major depressive, dysthymic, and anxiety disorders (panic disorder, agoraphobia,
      social phobia, and general anxiety disorder) in visually impaired older adults
      and compared these estimates with those of normally sighted peers. METHODS: Cross
      sectional data were analyzed based on telephone interviews with visually impaired
      older adults aged >= 60 years (n = 615) with a visual acuity of >= 0.30 logMAR
      (20/40 Snellen) in the best eye from outpatient low vision rehabilitation
      centers, and face-to-face interviews with community-dwelling normally sighted
      peers (n = 1232). To determine prevalence rates, the normally sighted population
      was weighted on sex and age to fit the visually impaired population. Logistic
      regression analyses were used to compare the populations and to correct for
      confounders. RESULTS: The prevalence of major depressive disorder (5.4%) and
      anxiety disorders (7.5%), as well as the prevalence of subthreshold depression
      (32.2%) and subthreshold anxiety (15.6%), were significantly higher in visually
      impaired older adults compared to their normally sighted peers (P < 0.05).
      Agoraphobia and social phobia were the most prevalent anxiety disorders in
      visually impaired older adults. CONCLUSIONS: This study shows that depression and
      anxiety are major public health problems in visually impaired older adults.
      Research on psychotherapeutic and psychopharmacologic interventions to improve
      depression and anxiety in this population is warranted.
      (http://www.trialregister.nl number, NTR3296.).

PMID- 25604691
TI  - High-resolution color-Doppler ultrasound for the study of skin growths.
AB  - High-resolution (17 MHz) color-Doppler ultrasound (US) is used in the evaluation
      of normal and pathological skin. To analyze retrospectively the sonographic
      pattern of healthy skin and of some skin lesions using Doppler US and to compare
      the results with dermoscopy examination and histology to identify specific
      patterns of ultrasound for differentiating benign from malignant lesions. To
      select among them the Melanomas to describe their US pattern, the presence and
      morphology of vascular signal and to compare their thickness at US with the
      Breslow index. After signing informed consent in accordance with the ethical
      standards laid down in the Declaration of Helsinki in 1964 and its subsequent
      amendments, 104 patients with skin lesions were retrospectively studied. Patients
      were evaluated with clinical dermatological examination and Doppler US, and
      underwent surgical excision with subsequent histological analysis. STATISTICAL
      ANALYSIS: the difference between variables was analyzed with statistical Chi
      square test or Fisher's when appropriate. The strength of the relationship
      between variables was analyzed with Pearson's r coefficient. The sensitivity and
      specificity of US tests were also calculated. Sixty-five malignant lesions and 39
      benign lesions were identified at Doppler US. In the 34 melanomas, typical US and
      vascular patterns were identified depending on the thickness of the lesion and a
      strong correlation between the latter and Breslow index was confirmed. Doppler US
      is a valuable diagnostic tool for the study of skin and for pre-excision
      characterization of skin lesions.

PMID- 25604692
TI  - Comparative analysis of effects of cyclic uniaxial and equiaxial stretches on
      gene expression of human umbilical vein endothelial cells.
AB  - It has been well established that biomechanical environment can influence
      functionality of biological cells. There are evidences that show mechanical
      cyclic stretch can promote smooth muscle cell (SMC) markers in endothelial cells
      (ECs). The objective of this study was to determine whether mechanical stimuli in
      the forms of uniaxial and equiaxial cyclic stretches (UNCS and EQCS) can affect
      endothelial and smooth muscle gene expressions in mRNA level of human umbilical
      vein endothelial cells (HUVECs). For this purpose, 10% uniaxial UNCS and EQCS (60
      cycles/min for 24 h) were applied on HUVECs, and using real-time PCR expressions
      of three EC specific markers, vascular endothelial growth factor receptor-2
      (VEGFR-2, also known as FLK-1), von Willebrand Factor (vWF) and vascular
      endothelial-cadherin (VE-cadherin) and two SMC specific genes, alpha-smooth
      muscle actin (alpha-SMA) and smooth muscle myosin heavy chain (SMMHC) were
      quantified. Moreover, alterations in cell height were analyzed by atomic force
      microscopy (AFM). Results showed that cyclic UNCS for 24 h downregulated the
      expression of all EC markers and upregulated the expression of all SMC markers
      while low effects on HUVECs height were observed. Cyclic EQCS in the same
      conditions resulted in minor effect on SMC gene expression in HUVECs, while led
      to strong reduction in vWF with no significant change in other two endothelial
      genes. Cyclic EQCS considerably elevated cell height. Results proposed that ECs
      can transdifferentiate to SMC phenotype under specific microenvironmental
      conditions.

PMID- 25604694
TI  - A mechanistic proposal for the protodeboronation of neat boronic acids: boronic
      acid mediated reaction in the solid state.
AB  - A combined experimental and computational study suggests that a reduction in the
      entropy of activation in the solid state can lead to the protodeboronation of
      boronic acids. 

PMID- 25604695
TI  - Management of advanced bladder cancer in the era of targeted therapies.
AB  - Systemic chemotherapy is the standard treatment of advanced and metastatic
      urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy
      is ineffective in a significant number of patients, while side effects occur
      frequently. Detailed molecular-genetic investigations revealed a broad
      heterogeneity of underlying genomic mutations in UCB and led to the detection of
      cancer-specific therapeutic targets. These findings may allow a more tailored and
      individualized patient-based therapy, focusing on specific genomic variations,
      which may cause chemo-resistance in patients progressing or relapsing after
      standard chemotherapy. Targeted therapies hold the potential to be more effective
      in inhibiting cancer cell growth and progression, as well as to cause fewer side
      effects. While targeted therapies have been successfully established in the
      treatment of various malignancies including renal cell carcinoma, the clinical
      impact of these modern treatment strategies still remains unsettled for UCB. In
      this review, we comprehensively summarize the most current and relevant findings
      on targeted therapy in advanced and metastatic UCB, elucidating chances and
      limitations and discussing future perspectives. 

PMID- 25604696
TI  - The male infertility office visit.
AB  - One in six couples are infertile, and in 50% of these couples, a male factor
      plays a role. Therefore, it is imperative that physicians become comfortable in
      the basic evaluation of the infertile male. By performing a thorough history and
      physical examination, physicians can usually establish a differential diagnosis
      and proceed to laboratory testing that will help to establish an etiology for
      infertility. The purpose of this review is to provide general guidelines for a
      physician seeking to evaluate a man's fertility status and to suggest the most
      common pathologies that might be found through a directed work-up. 

PMID- 25604693
TI  - Global insights into high temperature and drought stress regulated genes by RNA
      Seq in economically important oilseed crop Brassica juncea.
AB  - BACKGROUND: Brassica juncea var. Varuna is an economically important oilseed crop
      of family Brassicaceae which is vulnerable to abiotic stresses at specific stages
      in its life cycle. Till date no attempts have been made to elucidate genome-wide
      changes in its transcriptome against high temperature or drought stress. To gain
      global insights into genes, transcription factors and kinases regulated by these
      stresses and to explore information on coding transcripts that are associated
      with traits of agronomic importance, we utilized a combinatorial approach of next
      generation sequencing and de-novo assembly to discover B. juncea transcriptome
      associated with high temperature and drought stresses. RESULTS: We constructed
      and sequenced three transcriptome libraries namely Brassica control (BC),
      Brassica high temperature stress (BHS) and Brassica drought stress (BDS). More
      than 180 million purity filtered reads were generated which were processed
      through quality parameters and high quality reads were assembled de-novo using
      SOAPdenovo assembler. A total of 77750 unique transcripts were identified out of
      which 69,245 (89%) were annotated with high confidence. We established a subset
      of 19110 transcripts, which were differentially regulated by either high
      temperature and/or drought stress. Furthermore, 886 and 2834 transcripts that
      code for transcription factors and kinases, respectively, were also identified.
      Many of these were responsive to high temperature, drought or both stresses.
      Maximum number of up-regulated transcription factors in high temperature and
      drought stress belonged to heat shock factors (HSFs) and dehydration responsive
      element-binding (DREB) families, respectively. We also identified 239 metabolic
      pathways, which were perturbed during high temperature and drought treatments.
      Analysis of gene ontologies associated with differentially regulated genes
      forecasted their involvement in diverse biological processes. CONCLUSIONS: Our
      study provides first comprehensive discovery of B. juncea transcriptome under
      high temperature and drought stress conditions. Transcriptome resource generated
      in this study will enhance our understanding on the molecular mechanisms involved
      in defining the response of B. juncea against two important abiotic stresses.
      Furthermore this information would benefit designing of efficient crop
      improvement strategies for tolerance against conditions of high temperature
      regimes and water scarcity.

PMID- 25604697
TI  - Decellularized scaffolds containing hyaluronic acid and EGF for promoting the
      recovery of skin wounds.
AB  - There is no effective therapy for the treatment of deep and large area skin
      wounds. Decellularized scaffolds can be prepared from animal tissues and
      represent a promising biomaterial for investigation in tissue regeneration
      studies. In this study, MTT assay showed that epidermal growth factor (EGF)
      increased NIH3T3 cell proliferation in a bell-shaped dose response, and the
      maximum cell proliferation was achieved at a concentration of 25 ng/ml.
      Decellularized scaffolds were prepared from pig peritoneum by a series of
      physical and chemical treatments. Hyaluronic acid (HA) increased EGF adsorption
      to the scaffolds. Decellularized scaffolds containing HA sustained the release of
      EGF compared to no HA. Rabbits contain relatively large skin surface and are less
      expensive and easy to be taken care, so that a rabbit wound healing model was use
      in this study. Four full-thickness skin wounds were created in each rabbit for
      evaluation of the effects of the scaffolds on the skin regeneration. Wounds
      covered with scaffolds containing either 1 or 3 MUg/ml EGF were significantly
      smaller than with vaseline oil gauzes or with scaffolds alone, and the wounds
      covered with scaffolds containing 1 MUg/ml EGF recovered best among all four
      wounds. Hematoxylin-Eosin staining confirmed these results by demonstrating that
      significantly thicker dermis layers were also observed in the wounds covered by
      the decellularized scaffolds containing HA and either 1 or 3 MUg/ml EGF than with
      vaseline oil gauzes or with scaffolds alone. In addition, the scaffolds
      containing HA and 1 MUg/ml EGF gave thicker dermis layers than HA and 3 MUg/ml
      EGF and showed the regeneration of skin appendages on day 28 post
      transplantation. These results demonstrated that decellularized scaffolds
      containing HA and EGF could provide a promising way for the treatment of human
      skin injuries. 

PMID- 25604698
TI  - Influence of matrix and filler fraction on biofilm formation on the surface of
      experimental resin-based composites.
AB  - The aim of this study was to investigate the impact of resin matrix chemistry and
      filler fraction on biofilm formation on the surface of experimental resin-based
      composites (RBCs). Specimens were prepared from eight experimental RBC
      formulations differing in resin matrix blend (BisGMA/TEGDMA in a 7:3 wt% ratio or
      UDMA/aliphatic dimethacrylate in a 1:1 wt% ratio) and filler fraction (no
      fillers; 65 wt% dental glass with an average diameter of 7 or 0.7 um or 65 wt%
      SiO2 with an average diameter of 20 nm). Surface roughness, surface free energy,
      and chemical surface composition were determined; surface topography was
      visualized using atomic force microscopy. Biofilm formation was simulated under
      continuous flow conditions for a 48 h period using a monospecies Streptococcus
      mutans and a multispecies biofilm model. In the monospecies biofilm model, the
      impact of the filler fraction overruled the influence of the resin matrix,
      indicating lowest biofilm formation on RBCs with nano-scaled filler particles and
      those manufactured from the neat resin blends. The multispecies model suggested a
      more pronounced effect of the resin matrix blend, as significantly higher biofilm
      formation was identified on RBCs with a UDMA/dimethacrylate matrix blend than on
      those including a BisGMA/TEGDMA matrix blend but analogous filler fractions.
      Although significant differences in surface properties between the various
      materials were identified, correlations between the surface properties and
      biofilm formation were poor, which highlights the relevance of surface topography
      and chemistry. These results may help to tailor novel RBC formulations which
      feature reduced biofilm formation on their surface.

PMID- 25604699
TI  - Development of duloxetine hydrochloride loaded mesoporous silica nanoparticles:
      characterizations and in vitro evaluation.
AB  - This study investigated the potential use of mesoporous silica nanoparticles
      (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid
      degradation. Sol-gel and solvothermal methods were used to synthesize the MSNs,
      which, after calcination and drug loading, were then characterized using X-ray
      diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric
      analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning
      electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse
      reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from
      the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%).
      In a comparative release study between the MSNs in phosphate buffer, TW60-3DX
      showed sustained release for 140 h, which was higher than the other
      nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas
      kinetics model. The "n" value of all three MSNs ranged from 0.45 to 1 with a
      correlation coefficient (r (2)) >0.9, which indicated that the release of the
      drug from the system follows the anomalous transport or non-Fickian diffusion.
      The results supported the efficacy of mesoporous silica nanoparticles synthesized
      here as a promising carrier for duloxetine hydrochloride with higher drug loading
      and greater pH-sensitive release. 

PMID- 25604701
TI  - Invasion genetics of the Bermuda buttercup (Oxalis pes-caprae): complex
      intercontinental patterns of genetic diversity, polyploidy and heterostyly
      characterize both native and introduced populations.
AB  - Genetic diversity in populations of invasive species is influenced by a variety
      of factors including reproductive systems, ploidy level, stochastic forces
      associated with colonization and multiple introductions followed by admixture.
      Here, we compare genetic variation in native and introduced populations of the
      clonal plant Oxalis pes-caprae to investigate the influence of reproductive mode
      and ploidy on levels of diversity. This species is a tristylous geophyte native
      to South Africa. Invasive populations throughout much of the introduced range are
      composed of a sterile clonal pentaploid short-styled form. We examined morph
      ratios, ploidy level, reproductive mode and genetic diversity at nuclear
      microsatellite loci in 10 and 12 populations from South Africa and the Western
      Mediterranean region, respectively. Flow cytometry confirmed earlier reports of
      diploids and tetraploids in the native range, with a single population containing
      pentaploid individuals. Introduced populations were composed mainly of
      pentaploids, but sexual tetraploids were also found. There was clear genetic
      differentiation between ploidy levels, but sexual populations from both regions
      were not significantly different in levels of diversity. Invasive populations of
      the pentaploid exhibited dramatically reduced levels of diversity but were not
      genetically uniform. The occurrence of mixed ploidy levels and stylar
      polymorphism in the introduced range is consistent with multiple introductions to
      the Western Mediterranean. This inference was supported by variation patterns at
      microsatellite loci. Our study indicates that some invasive populations of Oxalis
      pes-caprae are not entirely clonal, as often assumed, and multiple introductions
      and recombination have the potential to increase genetic variation in the
      introduced range. 

PMID- 25604702
TI  - Radio-telemetry shows differences in the behaviour of wild and hatchery-reared
      European grayling Thymallus thymallus in response to environmental variables.
AB  - Juvenile wild and hatchery-reared European grayling Thymallus thymallus were
      tagged with radio-transmitters and tracked in the Blanice River, River Elbe
      catchment, Czech Republic, to study their behavioural response to stocking and
      environmental variation. Both wild and hatchery-reared T. thymallus increased
      their diel movements and home range with increasing light intensity, flow,
      temperature and turbidity, but the characteristics of their responses differed.
      Environmental variables influenced the movement of wild T. thymallus up to a
      specific threshold, whereas no such threshold was observed in hatchery-reared T.
      thymallus. Hatchery-reared fish displayed greater total migration distance over
      the study period (total migration) than did wild fish, which was caused mainly by
      their dispersal in the downstream direction.

PMID- 25604703
TI  - Tetraguanidino-functionalized phenazine and fluorene dyes: synthesis, optical
      properties and metal coordination.
AB  - In this work the first phenazine derivatives with guanidino substituents were
      prepared and their structural and electronic properties studied in detail. The
      guanidino groups decrease the HOMO-LUMO gap, massively increase the quantum yield
      for fluorescence and offer sites for metal coordination. The yellow-orange
      colored 2,3,7,8-tetraguanidino-substituted phenazine shows intense fluorescence.
      The wavelength of the fluorescence signal is strongly solvent dependent, covering
      a region from 515 nm in Et2O solution (with a record quantum yield of 0.39 in
      Et2O) to 640 nm in water. 2,3-Bisguanidino-substituted phenazine is less
      fluorescent (maximum quantum yield of 0.17 in THF), but exhibits extremely large
      Stokes shifts. In contrast, guanidino-functionalized fluorenes emit only very
      weakly. Subsequently, the influence of coordination on the electronic properties
      and especially the fluorescence of the phenazine system was analysed.
      Coordination first takes place at the guanidino groups, and leads to a blue shift
      of the luminescence signal as well as a massive decrease of the luminescence
      lifetime. Luminescence is almost quenched completely upon Cu(I) coordination. On
      the other hand, in the case of Zn(II) coordination the fluorescence signal
      remains strong (quantum yield of 0.36 in CH3CN). In the case of strong zinc Lewis
      acids, an excess of metal compound leads to additional coordination at the
      phenazine N atoms. This is accompanied by significant red-shifts of the lowest
      energy transition in the absorption and fluorescence spectra. Pentanuclear
      complexes with two phenazine units were isolated and structurally characterized,
      and further aggregation leads to chain polymers. 

PMID- 25604700
TI  - Development of acid-resistant alginate/trimethyl chitosan nanoparticles
      containing cationic beta-cyclodextrin polymers for insulin oral delivery.
AB  - In this study, the use of trimethylchitosan (TMC), by higher solubility in
      comparison with chitosan, in alginate/chitosan nanoparticles containing cationic
      beta-cyclodextrin polymers (CPbetaCDs) has been studied, with the aim of
      increasing insulin uptake by nanoparticles. Firstly, TMCs were synthesized by
      iodomethane, and CPbetaCDs were synthesized within a one-step polycondensation
      reaction using choline chloride (CC) and epichlorohydrine (EP). Insulin-CbetaCDPs
      complex was prepared by mixing 1:1 portion of insulin and CPbetaCDs solutions.
      Then, nanoparticles prepared in a three-step procedure based on the iono-tropic
      pregelation method. Nanoparticles screened using experimental design and Placket
      Burman methodology to obtain minimum size and polydispercity index (pdI) and the
      highest entrapment efficiency (EE). CPbetaCDs and TMC solution concentration and
      pH and alginate and calcium chloride solution concentrations are found as the
      significant parameters on size, PdI, and EE. The nanoparticles with proper
      physicochemical properties were obtained; the size, PdI, and EE% of optimized
      nanoparticles were reported as 150.82 +/- 21 nm, 0.362 +/- 0.036, and 93.2% +/-
      4.1, respectively. The cumulative insulin release in intestinal condition
      achieved was 50.2% during 6 h. By SEM imaging, separate, spherical, and
      nonaggregated nanoparticles were found. In the cytotoxicity studies on Caco-2
      cell culture, no significant cytotoxicity was observed in 5 h of incubation, but
      after 24 h of incubation, viability was decreased to 50% in 0.5 mMU of TMC
      concentration. Permeability studies across Caco-2 cells had been carried out, and
      permeability achieved in 240 min was 8.41 +/- 0.39%, which shows noticeable
      increase in comparison with chitosan nanoparticles. Thus, according to the
      results, the optimized nanoparticles can be used as a new insulin oral delivery
      system. 

PMID- 25604704
TI  - Prevalence and predictors of adolescents' cigarette smoking in Madinah, Saudi
      Arabia: a school-based cross-sectional study.
AB  - BACKGROUND: Although the prevalence of adolescents' cigarette smoking has
      increased in recent decades, little is known regarding its epidemiology in
      certain Saudi regions, including the Madinah region. The aim of this study was to
      determine the prevalence and predictors of adolescent cigarette smoking in
      Madinah, Saudi Arabia. METHODS: A school-based cross-sectional study was carried
      out in the Madinah region during 2013. A multistage stratified cluster sample was
      taken and included 3400 students (11-19 years) from 34 intermediate and secondary
      schools. Data concerning sociodemographic and smoking-related factors were
      collected using a valid and reliable self-administered questionnaire. The
      prevalence of smoking was estimated, and appropriate statistical analyses were
      performed, including univariate, predictive and multivariate regression analyses.
      RESULTS: The overall response rate was 97.7%. The prevalence of cigarette smoking
      in the respondents' 3322 adolescents was 15.17% (95% CI = 13.95-16.39) with
      significant differences in sociodemographic factors. The most important
      predictors were most or all friends smoking (OR = 12.5; 95% CI = 9.40-16.8).
      Other significant less important factors were parental smoking, belief in the
      harmful effects of smoking, cigarette advertisement in mass media, and pocket
      money. CONCLUSIONS: Cigarette smoking prevalence is a relatively low among
      adolescents in Madinah region. However, friends and parents smoking play an
      important role in the increased risk of smoking in the studied adolescents. These
      predictors must be included in any antismoking education programs targeting to
      this sector of population in the region.

PMID- 25604705
TI  - Accounting for sex differences in PTSD: A multi-variable mediation model.
AB  - BACKGROUND: Approximately twice as many females as males are diagnosed with
      posttraumatic stress disorder (PTSD). However, little is known about why females
      report more PTSD symptoms than males. Prior studies have generally focused on few
      potential mediators at a time and have often used methods that were not ideally
      suited to test for mediation effects. Prior research has identified a number of
      individual risk factors that may contribute to sex differences in PTSD severity,
      although these cannot fully account for the increased symptom levels in females
      when examined individually. OBJECTIVE: The present study is the first to
      systematically test the hypothesis that a combination of pre-, peri-, and
      posttraumatic risk factors more prevalent in females can account for sex
      differences in PTSD severity. METHOD: The study was a quasi-prospective
      questionnaire survey assessing PTSD and related variables in 73.3% of all Danish
      bank employees exposed to bank robbery during the period from April 2010 to April
      2011. Participants filled out questionnaires 1 week (T1, N=450) and 6 months
      after the robbery (T2, N=368; 61.1% females). Mediation was examined using an
      analysis designed specifically to test a multiple mediator model. RESULTS:
      Females reported more PTSD symptoms than males and higher levels of neuroticism,
      depression, physical anxiety sensitivity, peritraumatic fear, horror, and
      helplessness (the A2 criterion), tonic immobility, panic, dissociation, negative
      posttraumatic cognitions about self and the world, and feeling let down. These
      variables were included in the model as potential mediators. The combination of
      risk factors significantly mediated the association between sex and PTSD
      severity, accounting for 83% of the association. CONCLUSION: The findings suggest
      that females report more PTSD symptoms because they experience higher levels of
      associated risk factors. The results are relevant to other trauma populations and
      to other trauma-related psychiatric disorders more prevalent in females, such as
      depression and anxiety.

PMID- 25604706
TI  - A psychoanalytic child psychotherapy contribution to generic assessments.
AB  - Psychoanalytically trained child and adolescent psychotherapists have applied
      psychodynamic thinking to family work, consultations and brief work for some
      time. Findings from a research project in which the author investigated the
      processes involved in generic assessments undertaken by herself and what actually
      takes place are presented. A description of some skills and techniques used by
      the author are also described. 

PMID- 25604708
TI  - Strain driven monoclinic distortion of ultrathin CoO films in the exchange
      coupled CoO/FePt/Pt(0 0 1) system.
AB  - The structure and strain of ultrathin CoO films grown on a Pt(0 0 1) substrate
      and on a ferromagnetic FePt pseudomorphic layer on Pt(0 0 1) have been determined
      with in situ and real time surface x-ray diffraction. The films grow epitaxially
      on both surfaces with an in-plane hexagonal pattern that yields a pseudo-cubic
      CoO(1 1 1) surface. A refined x-ray diffraction analysis reveals a slight
      monoclinic distortion at RT induced by the anisotropic stress at the interface.
      The tetragonal contribution to the distortion results in a ratio [Formula: see
      text], opposite to that found in the low temperature bulk CoO phase. This
      distortion leads to a stable Co(2+) spin configuration within the plane of the
      film. 

PMID- 25604707
TI  - Insights into bacterial colonization of intensive care patients' skin: the effect
      of chlorhexidine daily bathing.
AB  - Skin is a major reservoir of bacterial pathogens in intensive care unit (ICU)
      patients. The aim of this study was to assess the skin bacterial richness and
      diversity in ICU patients and the effect of CHG daily bathing on skin microbiota.
      Twenty ICU patients were included during an interventional period with CHG daily
      bathing (n = 10) and a control period (n = 10). At day seven of hospitalization,
      eight skin swab samples (nares, axillary vaults, inguinal creases, manubrium and
      back) were taken from each patient. The bacterial identification was performed by
      microbial culturomics. We used the Shannon index to compare the diversity. We
      obtained 5,000 colonies that yielded 61 bacterial species (9.15 +/- 3.7 per
      patient), including 15 (24.5 %) that had never been cultured from non
      pathological human skin before, and three (4.9 %) that had never been cultured
      from human samples before. Notably, Gram-negative bacteria were isolated from all
      sites. In the water-and-soap group, there was a higher risk of colonization with
      Gram-negative bacteria (OR = 6.05, 95 % CI [1.67-21.90]; P = 0.006). In the CHG
      group, we observed more patients colonized by sporulating bacteria (9/10 vs.
      3/10; P = 0.019) with a reduced skin bacterial richness (P = 0.004) and lower
      diversity (0.37, 95 % CI [0.33; 0.42] vs. 0.50, 95 % CI [0.48; 0.52]). Gram
      negative bacteria are frequent and disseminated components of the transient skin
      flora in ICU patients. CHG daily bathing is associated with a reduction in Gram
      negative bacteria colonization together with substantial skin microbiota shifts. 

PMID- 25604709
TI  - Responses of artificially reared cat fleas Ctenocephalides felis felis (Bouche,
      1835) to different mammalian bloods.
AB  - The cat flea, Ctenocephalides felis felis (Bouche, 1835) (Siphonaptera:
      Pulicidae), which is found worldwide and which parasitizes many species of wild
      and domestic animal, is a vector and/or reservoir of bacteria, protozoa and
      helminths. To aid in the study of the physiology and behaviour of fleas and of
      their transmission of pathogens, it would be of value to improve the laboratory
      rearing of pathogen-free fleas. The conditions under which artificially reared
      fleas at the University of Bristol (U.K.) and the Rickettsial Diseases Institute
      (France) are maintained were studied, with different ratios of male to female
      fleas per chamber (25 : 50, 50 : 100, 100 : 100, 200 : 200). The fleas were fed
      with bovine, ovine, caprine, porcine or human blood containing the anticoagulants
      sodium citrate or EDTA. Egg production was highest when fleas were kept in
      chambers with a ratio of 25 males to 100 females. In addition, the use of EDTA as
      an anticoagulant rather than sodium citrate resulted in a large increase in the
      number of eggs produced per female; however, the low percentage of eggs
      developing through to adult fleas was lower with EDTA. The modifications
      described in our rearing methods will improve the rearing of cat fleas for
      research.

PMID- 25604710
TI  - Delafloxacin for the treatment of respiratory and skin infections.
AB  - INTRODUCTION: There has been a striking increase in the emergence of multidrug
      resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum
      fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram
      negative and anaerobic organisms. It has the potential to treat a variety of
      infections including complicated skin and skin structure infections and
      respiratory tract infections. AREAS COVERED: In this review, the authors report
      the microbiological spectrum of activity of delafloxacin as well as its
      pharmacokinetic characteristics. They also report the results of recent studies
      investigating its safety and efficacy. EXPERT OPINION: The profile of
      delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of
      activity against pathogens involved in respiratory infections and complicated
      skin and skin structure infections (SSSIs), including methicillin-resistant
      Staphylococcus aureus. It has also shown activity against Gram-negative
      pathogens, such as quinolone-susceptible and -resistant strains of Escherichia
      coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa.
      The availability of an oral formulation supports its use in sequential therapy.
      The efficacy and tolerability of delafloxacin have been demonstrated in Phase II
      clinical trials in comparison with moxifloxacin for respiratory infections and
      linezolid and vancomycin in SSSIs. Compared with other quinolones such as
      moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse
      effects. The results of new Phase III studies are awaited to confirm
      delafloxacin's future applications in the treatment of SSSIs.

PMID- 25604711
TI  - The future of monitoring molecules.

PMID- 25604713
TI  - Social media makes global urology meetings truly global. : The influence of
      Twitter.

PMID- 25604714
TI  - How active should active surveillance be?

PMID- 25604715
TI  - Conventional laparoscopic surgery: more pain, no gain!

PMID- 25604716
TI  - Opening the flood gates: holmium laser enucleation is superior to photoselective
      vaporization of the prostate for the treatment of chronic urinary retention.

PMID- 25604717
TI  - Malignant medication? Testosterone and cancer.

PMID- 25604718
TI  - 19-Year-Old Male With a History of Recurrent Episodes of Calf Pain, Headache, and
      Fever.

PMID- 25604719
TI  - Breed of boar influences the optimal concentration of gamma-oryzanol needed for
      semen cryopreservation.
AB  - The aim of this study was to investigate the influence of boar breed on the
      optimal concentration of gamma-oryzanol on the qualities of cryopreserved boar
      semen. Semen was collected from 20 boars (10 Duroc, 5 Large white and 5 Landrace
      boars). The semen sample was divided into five groups (A-E) according to the
      concentration of gamma-oryzanol in extender II, that is 0, 0.08, 0.16, 0.24 and
      0.32 mM, respectively. The semen was cryopreserved by nitrogen vapour and storage
      in nitrogen tank (-196 degrees C). After storage for a week, samples were thawed
      at 50 degrees C for 12 s and evaluated for progressive motility, sperm viability
      and acrosome integrity. The results demonstrated that gamma-oryzanol
      significantly improved progressive motility, viability and acrosome integrity of
      frozen-thawed boar semen. Considering the influence of breeds on the optimal
      concentration of gamma-oryzanol, for Duroc boar, gamma-oryzanol at 0.16 mM (group
      C) yielded the highest percentage of progressive motility, sperm viability and
      acrosome integrity. For Large white and Landrace boars, gamma-oryzanol at 0.24 mM
      (group D) showed a significantly higher percentage of progressive motility,
      viability (not significant in Landrace) and acrosome integrity than other
      concentrations. In conclusion, the optimal concentration of gamma-oryzanol needed
      for boar semen cryopreservation in lactose-egg yolk (LEY) freezing extender is
      not only depended on individual boar but also breed of boar, that is 0.16 mM for
      Duroc and 0.24 mM for Large white and Landrace.

PMID- 25604720
TI  - Clinical risk factors of prediabetes in Taiwanese women without substance uses
      (tobacco, alcohol, or areca nut).
AB  - BACKGROUND/PURPOSE: Individuals with prediabetes (100-125 mg/dL) and diabetes
      mellitus (DM) increase the risk of all-cause and cardiovascular disease (CVD)
      mortality. Since personal substance use such as cigarette smoking, alcohol
      drinking, and areca nut chewing may confound the true effect of clinical
      biochemistries on the risk of prediabetes, this study aims to examine the
      relationship between clinical biochemical parameters and the risk of prediabetes
      among Taiwanese without the habits of consuming tobacco, alcohol drinking, or
      areca nut. METHODS: Women aged between 40 years and 64 years who came to one
      community teaching hospital between January 1, 2001 and December 31, 2008 for
      general health screening for the first time were studied. The general health
      screening is provided every 3 years gratis. The package of this health screening
      includes personal history, physical examination, and biochemical tests in serum
      and urine. RESULTS: In total, 8580 nonsmoking, nondrinking, and nonareca nut
      chewing women who did not have a history of DM were eligible for this study. Of
      these, 1861 (21.7%) out of 8580 women were prediabetic. Compared to women with
      normal fasting glucose (NFG), we found a dose-response relationship of the risk
      of prediabetes with age and body mass index (BMI) and total cholesterol,
      triglyceride, glutamic-pyruvic transaminase (GPT), and uric acid in serum. Women
      with hypertension or proteinuria (>=30 mg/dL) had also an increased risk to have
      prediabetes. CONCLUSION: Besides age, the factors of BMI, hypertension,
      dyslipidemia, GPT, hyperuricemia, and proteinuria are the main risk factors for
      prediabetes in Taiwanese women without substance uses. A follow-up study is
      necessary to clarify the causality of these important biochemical parameters and
      prediabetes.

PMID- 25604721
TI  - Efficacy of porcine antihuman lymphocyte immunoglobulin compared to rabbit
      antithymocyte immunoglobulin as a first-line treatment against acquired severe
      aplastic anemia.
AB  - Immunosuppressive therapy (IST) with antithymocyte immunoglobulin (ATG) or
      antilymphocyte immunoglobulin (ALG) and cyclosporine A (CsA) is the treatment of
      choice against severe aplastic anemia (SAA) worldwide. However, a comparison of
      the efficacy of porcine ALG (pALG) and rabbit ATG (rATG) as a first-line
      treatment for acquired SAA has not been reported. In the present study, we
      retrospectively analyzed SAA patients treated with either pALG (n = 43) or rATG
      (n = 32) and compared their hematologic responses and survivals. There were no
      significant differences in overall response (OR) rates between pALG and rATG
      groups at 3 months (OR 41.86 versus 40.62% (P = 0.914), 6 months (OR 66.67 versus
      61.29% (P = 0.635), 9 months (OR 69.05 versus 61.29% (P = 0.490), or 12 months
      (OR 69.05 versus 64.51% (P = 0.684), respectively. The OR rates in patients with
      SAA or very severe aplastic anemia (vSAA) in both groups were similar after a 12
      month treatment (pALG 74.07 versus 60.00%, P = 0.550; rATG 70.00 versus 54.55%, P
      = 0.640). Patients who experienced <30-day interval between diagnosis and
      treatment displayed higher OR rates (at 12 months) than those with intervals >=30
      days (pALG 83.33 versus 50.00%, P = 0.021; rATG 87.50 versus 40.00%, P = 0.006).
      There were no significant differences in 2-year overall survival (OS) between
      pALG (87.4 +/- 6.2%) and rATG (83.2 +/- 7.8%) (P = 0.493). Infection was the
      major cause of death in both groups. In summary, pALG + CsA showed similar
      efficacy as rATG + CsA, as a first-line treatment for acquired SAA.

PMID- 25604723
TI  - Factors influencing prehospital delay time among patients with peripheral
      arterial occlusive disease.
AB  - BACKGROUND: Only one-third of patients with peripheral arterial occlusive disease
      (PAOD) seek medical care after perceiving the symptoms of PAOD, and most PAOD
      patients only visit the physician when they develop ulceration and gangrene.
      Delay can result in lower extremity amputation and death within three years. The
      aim of this study was to predict prehospital delay time from sociodemographic
      characteristics and clinical characteristics, social support, knowledge about
      PAOD, depression and fear, and treatment-seeking behaviors among patients with
      PAOD. METHOD AND RESULTS: Data were collected in three university hospitals in
      Bangkok, Thailand. A sample of 212 patients with PAOD who were newly diagnosed or
      diagnosed within the preceding four months was recruited into the study.
      Questionnaires and interviewing were used to collect data. Stepwise multiple
      regression analysis was performed to identify the factors influencing prehospital
      delay time. Significant determinants of prolonged prehospital delay time were
      male gender, low monthly income (less than 10,000 Thai baht or 213 Euros), high
      level of perceived social support, and several treatment seeking behaviors.
      Depression, high level of fear, and self-pay of medical expenses were associated
      with short prehospital delay time. Overall, the model explained 41.0% of the
      variance in prehospital delay time. CONCLUSION: Clinicians need to develop
      intervention programs and national campaigns to increase knowledge about PAOD
      among patients in these high risk groups.

PMID- 25604725
TI  - Anti-hyperalgesic activity of crude extract and 7-methyljuglone of Diospyros
      lotus roots.
AB  - This study was designed to evaluate the antihyperalgesic effect of crude extract
      of Diospyros lotus followed by the isolation and characterisation of 7
      methyljuglone in acetic acid and formalin tests. The pretreatment of crude
      extract evoked dose-dependent inhibition of noxious stimulation with maximum
      effect of 56.78% in acetic acid-induced writhing test, which were 51.89% and
      60.69% in first and second phases, respectively, at 100 mg/kg i.p. The structure
      of 7-methyljuglone was confirmed by spectroscopic analysis. 7-Methyljuglone
      evoked profound increase in pain threshhold dose dependently; when it was studied
      in acetic acid-induced writhing test with 63.73% pain attenuation while 51.22%
      and 65.44% pain amelioration in first and second phases, respectively, at 100
      mg/kg i.p. In conclusion, crude extract and 7-methyljuglone of D. lotus roots
      possessed both peripheral and central antinociceptive potential and thus could be
      a useful new therapeutic agent.

PMID- 25604722
TI  - Impact of milk consumption on cardiometabolic risk in postmenopausal women with
      abdominal obesity.
AB  - BACKGROUND: The impact of dairy intake on cardiometabolic risk factors associated
      with metabolic syndrome (MetS) needs further research. OBJECTIVE: To investigate
      the impact of milk consumption on a wide array of cardiometabolic risk factors
      associated with MetS (blood lipids, cholesterol homeostasis, glucose homeostasis,
      systemic inflammation, blood pressure, endothelial function) in postmenopausal
      women with abdominal obesity. METHODS: In this randomized, crossover study, 27
      women with abdominal obesity consumed two 6-week diets based on the National
      Cholesterol Education Program (NCEP), one with 3.2 servings/d of 2% fat milk per
      2000 kcal (MILK) and one without milk or other dairy (NCEP). The macronutrient
      composition of both diets was comparable (55% carbohydrates, 15% proteins, 30%
      fat and 10% saturated fat). RESULTS: The MILK diet had no significant effect on
      LDL-C, triglycerides, LDL size, CRP and cell adhesion molecule concentrations and
      on indicators of insulin sensitivity. The MILK diet reduced HDL-C, adiponectin,
      endothelin and fasting glucose levels as well blood pressure (all P <= 0.01), but
      those changes were comparable to those seen with the NCEP milk-free diet (all
      between-diet P >= 0.07). Finally, the MILK diet was associated with lower VLDL
      apolipoprotein B fractional catabolic rate (-13.4%; P = 0.04) and plasma sterol
      concentrations (-12.0%; P = 0.04) compared with the control NCEP milk-free diet.
      CONCLUSIONS: These data suggest that short-term consumption of low fat milk in
      the context of a prudent NCEP diet has no favorable nor deleterious effect on
      cardiometabolic risk factors associated with MetS in postmenopausal women with
      abdominal obesity.

PMID- 25604727
TI  - Bifidobacterium bifidum R0071 results in a greater proportion of healthy days and
      a lower percentage of academically stressed students reporting a day of cold/flu:
      a randomised, double-blind, placebo-controlled study.
AB  - Acute psychological stress is positively associated with a cold/flu. The present
      randomised, double-blind, placebo-controlled study examined the effect of three
      potentially probiotic bacteria on the proportion of healthy days over a 6-week
      period in academically stressed undergraduate students (n 581) who received
      Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033,
      Bifidobacterium bifidum R0071 or placebo. On each day, participants recorded the
      intensity (scale: 0 = not experiencing to 3 = very intense) for nine cold/flu
      symptoms, and a sum of symptom intensity >6 was designated as a day of cold/flu.
      B. bifidum resulted in a greater proportion of healthy days than placebo (P<=
      0.05). The percentage of participants reporting >= 1 d of cold/flu during the 6
      week intervention period was significantly lower with B. bifidum than with
      placebo (P< 0.05). There were no effects of B. infantis or L. helveticus compared
      with placebo on either outcome. A predictive model accounted for influential
      characteristics and their interactions on daily reporting of cold/flu episodes.
      The proportion of participants reporting a cold on any given day was lower at
      weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average
      level of stress and the most commonly reported number of hours of sleep. Daily
      intake of bifidobacteria provides benefit related to cold/flu outcomes during
      acute stress. 

PMID- 25604726
TI  - Intraoperative ultrasonography for the identification of thoracic recurrent
      laryngeal nerve lymph nodes in patients with esophageal cancer.
AB  - The rate of vocal cord palsy following resection for esophageal carcinoma has
      increased due to lymphadenectomy around the recurrent laryngeal nerves (RLN). The
      aim of this pilot study was to assess the ability of intraoperative
      ultrasonography to detect thoracic RLN node metastases in patients with
      esophageal cancer. Intraoperative ultrasonography was performed during
      esophagectomy to assess whether RLN lymph nodes were metastatic in 10 patients
      with esophageal squamous cell cancer. All patients underwent RLN lymphadenectomy,
      and the nodes were assessed for metastasis. Three patients had pathological RLN
      lymph node metastases, of which one had right RLN node metastasis, and three had
      left RLN node metastases. For detecting right RLN lymph node metastasis, the
      sensitivity, specificity, and positive and negative predictive values of
      intraoperative ultrasonography were 100%, 33.3%, 14.3%, and 100%, respectively.
      For the detection of left RLN lymph node, these values were 100%, 85.7%, 75%, and
      100%, respectively. This study suggests that intraoperative ultrasonography is
      feasible and safe to detect RLN lymph node metastases for patients with
      esophageal cancer. Further study will be performed to evaluate the validity and
      utility of this diagnostic technique. 

PMID- 25604728
TI  - A patchless dissolving microneedle delivery system enabling rapid and efficient
      transdermal drug delivery.
AB  - Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver
      encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are
      superimposed onto patches that facilitate their insertion into skin. However, due
      to wide variations in skin elasticity and the amount of hair on the skin, the
      arrays fabricated on the patch are often not completely inserted and large amount
      of loaded materials are not delivered. Here, we report "Microlancer", a novel
      micropillar based system by which patients can self-administer DMNs and which
      would also be capable of achieving 97 +/- 2% delivery efficiency of the loaded
      drugs regardless of skin type or the amount of hair on the skin in less than a
      second. 

PMID- 25604730
TI  - Applications of atomic layer deposition in solar cells.
AB  - Atomic layer deposition (ALD) provides a unique tool for the growth of thin films
      with excellent conformity and thickness control down to atomic levels. The
      application of ALD in energy research has received increasing attention in recent
      years. In this review, the versatility of ALD in solar cells will be discussed.
      This is specifically focused on the fabrication of nanostructured
      photoelectrodes, surface passivation, surface sensitization, and band-structure
      engineering of solar cell materials. Challenges and future directions of ALD in
      the applications of solar cells are also discussed. 

PMID- 25604729
TI  - Intensity-modulated proton therapy for elective nodal irradiation and involved
      field radiation in the definitive treatment of locally advanced non-small-cell
      lung cancer: a dosimetric study.
AB  - BACKGROUND: Photon involved-field (IF) radiation therapy (IFRT), the standard for
      locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable
      outcomes without increased isolated nodal failures, perhaps from scattered dose
      to elective nodal stations. Because of the high conformality of intensity
      modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We
      investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA
      NSCLC. PATIENTS AND METHODS: IMPT IFRT plans were generated to the same total
      dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT.
      IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective
      nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. RESULTS: Proton
      IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the
      prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated
      dosimetric parameters improved significantly with both proton plans. The lung
      percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18%
      (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03)
      and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and
      12% with ENI; heart V25 decreased 63% with both (all P < .01). CONCLUSION: This
      study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased
      toxicity indicates that IMPT could allow ENI while maintaining a favorable
      therapeutic ratio compared with photon IFRT.

PMID- 25604733
TI  - Monoglyceride-based organogelator for broad-range oil uptake with high capacity.
AB  - Oil/water separation has been a worldwide subject because of increasing release
      of oil-containing wastewater as well as several marine oil spills. The phase
      selective organogelators (PSOGs) are thought to offer a potential and effective
      implement for addressing this issue. An ideal PSOG for oil adsorption must
      fulfill some requirements involving effective gelation, easy synthesis, low cost,
      and recyclable for reuse. However, beyond those, the ability of gelation for a
      broad-range oil phase without selectivity is also important. However, most of the
      reported PSOGs have limitation in this respect thus far. In this paper, a new
      class of saturated 1-monoglyceride-derived organogelators can efficiently uptake
      almost all of the common fuel oils from water and gelate organic solvents with
      extremely low minimum gelation concentration (MGC). In addition, the oils in the
      gel and gelator molecules can be recovered quantitatively through simple vacuum
      distillation. 

PMID- 25604731
TI  - An association of Aquaporin-4 with the immunoregulation of liver pathology in
      mice infected with Schistosoma japonicum.
AB  - BACKGROUND: Schistosomiasis is a chronic parasitic disease that affects
      approximately 200 million people. In Schistosomiasis japonica and mansoni,
      parasite eggs were trapped in host liver and stimulated the CD4(+)T cell
      responses to regulate the formation of the granulomas. Subsequently, excessive
      granulomatous response in some heavily, and/or repeatedly infected individuals
      could result in chronic liver fibrosis and circulatory impairment. Thus,
      elucidation of the mechanisms of these responses will not only provide more
      information to better understand the mechanisms of the immunoregulation in
      schistosomiasis, but also help to design new therapies to control granuloma
      associated immunopathology. The role of aquaporin-4 (AQP4) in water transport has
      been extensively investigated in the central nervous system (CNS). Recently,
      studies have shown that AQP4 expresses in immune system and lack of AQP4 in mice
      results in significantly less CD4(+)CD25(+) T regulatory cells (Treg cells) under
      physiological condition, one of the subpopulations of CD4(+)T cells which
      restrains immunopathology in hosts with schistosomiasis. However, little
      information exists regarding the contribution of AQP4 to the immune regulation in
      schistosome infection. METHODS: The liver granulomatous response in S. japonicum
      infected AQP4 knockout (KO) mice and its wild-type (WT) littermates were detected
      by staining liver sections with hematoxylin and eosin. The generation of various
      CD4(+) T subsets, including Th1, Th2, Th17, and Treg cells were analyzed by flow
      cytometry. In addition, the levels of total IgG, IgG1, IgG2a in serum of infected
      mice were detected by ELISA assay. RESULTS: Our results showed an enhanced
      granulomatous response with increased accumulation of eosinophils and macrophages
      around eggs in the liver of AQP4 KO mice with Schistosomiasis japonica. In
      addition, our study demonstrated enhanced Th2 but reduced Th1 and Treg cells
      generation in AQP4 KO mice with Schistosomiasis japonica, which may, at least
      partly, account for the enhancement of the liver granuloma formation. CONCLUSION:
      Our study for the first time provides evidences that AQP4 has an association with
      the immunoregulation of the liver granuloma formation, which may confer a new
      option for schistosomiasis treatment.

PMID- 25604732
TI  - Mertk deficiency alters expression of micrornas in the retinal pigment epithelium
      cells.
AB  - Phagocytic clearance of the spent photoreceptor outer segments (OS) by RPE cells
      is regulated by circadian rhythm cycle and is essential for photoreceptor
      integrity and function. Mertk regulates RPE phagocytosis and a deficiency in
      Mertk causes photoreceptor degeneration and visual loss. This study aimed to
      investigate Mertk regulation of the microRNAs (miRNA), potentially regulating
      expression of their target genes, which affect phagocytosis. The differentially
      expressed miRNAs were identified using miRCURY(TM) microRNA Arrays from total RNA
      isolated at 0900 h and 1900 h from the mechanically dissociated RPE sheets of the
      WT and Mertk (-/-) mice, which were housed in a 12-h light-dark cycle with the
      lighting onset at 0700 h (7:00am). Validation of the differentially expressed
      miRNAs and assessment of the putative miRNA target gene expression were performed
      by real-time PCR. Among the differentially expressed miRNAs in the Mertk (-/-)
      RPE, seven miRNAs were up-regulated and 13 were down-regulated in the morning
      groups. Similarly, 24 miRNAs were found to be up-regulated and 13 were down
      regulated in the evening groups. To search for those that may participate in
      regulating expression of cytoskeletal proteins, we examined the predicted target
      genes that might participate in phagocytosis were examined by real-time PCR. Of
      nine potential altered targets, four deregulated genes were myosin subunits.
      Notably, multiple members of the 21 up-regulated miRNAs can theoretically
      recognize these down-regulated mRNAs, particularly MyH14 and Myl3. This study
      shows that loss of Mertk alters miRNA expression, which in turn affects
      expression of the downstream target genes, potentially affecting phagocytosis. 

PMID- 25604734
TI  - Noninvasive in vivo confocal laser scanning microscopy is effective in
      differentiating allergic from nonallergic equivocal patch test reactions.
AB  - Patch testing is the gold standard for the validation of contact dermatitis. It
      relies on the subjective scoring by an evaluator of the inflammatory reaction
      induced by an allergen applied to the skin. Equivocal reactions imply faint
      erythema and could represent allergic, irritant, or negative reactions. They
      constitute approximately 1 % of the positive reactions encountered in patch test
      practice. Histological evaluation of the equivocal reaction has proven helpful
      for the correct interpretation but is however time consuming, and its invasive
      nature is often unacceptable to the patient. In vivo confocal laser scanning
      microscopy (CLSM) is a novel, noninvasive imaging technique which permits real
      time visualization of skin structures and lesions at a resolution close to that
      obtained by conventional histology. CLSM has been successfully applied for the
      differentiation between clinically clear-cut allergic and irritant patch test
      reactions. The objective of this study is to determine the relevance of CLSM in
      differentiating between allergic, irritant, and negative equivocal patch test
      reactions. Fifteen patients who underwent patch testing in our clinic were
      observed as having 20 equivocal reactions. All 20 reactions were evaluated using
      in vivo CLSM and compared with adjacent normal skin. In vivo CLSM evaluation
      revealed that 8 of the 20 equivocal reactions (40 %) showed confocal patterns
      consistent with the patterns encountered in positive allergic reactions.
      Anamnestic exposure, i.e., detailed assessment of previous related contact with
      these allergens, confirmed high relevance rates. In vivo CLSM is useful in
      differentiating between allergic, irritant, and negative equivocal patch test
      reactions, a differentiation that cannot be made by conventional clinical patch
      test reading.

PMID- 25604735
TI  - Cancer targeting with biomolecules: a comparative study of photodynamic therapy
      efficacy using antibody or lectin conjugated phthalocyanine-PEG gold
      nanoparticles.
AB  - The functionalisation of therapeutic nanoparticle constructs with cancer-specific
      biomolecules can enable selective tumour accumulation and targeted treatment.
      Water soluble gold nanoparticles (ca. 4 nm) stabilised by a mixed monolayer of a
      hydrophobic zinc phthalocyanine photosensitiser (C11Pc) and hydrophilic
      polyethylene glycol (PEG) have been prepared. The C11Pc-PEG gold nanoparticle
      constructs were further functionalised with jacalin, a lectin specific for the
      cancer-associated Thomsen-Friedenreich (T) carbohydrate antigen, or with
      monoclonal antibodies specific for the human epidermal growth factor receptor-2
      (HER-2). The two biofunctionalised nanoparticle conjugates produced similar
      levels of singlet oxygen upon irradiation at 633 nm. Importantly, both
      nanoparticle conjugates demonstrated extensive, yet comparable, phototoxicity in
      HT-29 colorectal adenocarcinoma cells (80-90%) and in SK-BR-3 breast
      adenocarcinoma cells (>99%). Non-conjugated C11Pc-PEG gold nanoparticles were
      only minimally phototoxic. Lysosomal colocalisation studies performed with the HT
      29 colon cancer cells and the SK-BR-3 breast cancer cells revealed that both
      nanoparticle conjugates were partially localised within acidic organelles, which
      is typical of receptor-mediated endocytosis. The similarity of the targeted PDT
      efficacy of the two biofunctionalised C11Pc-PEG gold nanoparticles is discussed
      with respect to targeting ligand binding affinity and cell surface antigen
      density as key determinants of targeting efficiency. This study highlights how
      targeting small cell-surface molecules, such as the T antigen, can mediate a
      selective photodynamic treatment response which is similar to that achieved when
      targeting overexpressed protein receptors, such as HER-2. The high prevalence of
      the T antigen present on the cellular surface of primary tumours emphasises the
      broad potential applications for lectin-targeted therapies. 

PMID- 25604736
TI  - Effects of polygamy on the activity/rest rhythm of male fruit flies Drosophila
      melanogaster.
AB  - Although polygamy is common in insects, its extent varies enormously among
      natural populations. Mating systems influence the evolution of reproductive
      traits and the difference in extent of polygamy between males and females may be
      a key factor in determining traits which come under the influence of sexual
      selection. Fruit flies Drosophila melanogaster are promiscuous as both males and
      females mate with multiple partners. Mating has severe consequences on the
      physiology and behaviour of flies, and it affects their activity/rest rhythm in a
      sex-specific manner. In this study, we attempted to discern the effects of mating
      with multiple partners as opposed to a single partner, or of remaining unmated,
      on the activity/rest rhythm of flies under cyclic semi-natural (SN) and constant
      dark (DD) conditions. The results revealed that while evening activity of mated
      flies was significantly reduced compared to virgins, polygamous males showed a
      more severe reduction compared to monogamous males. In contrast, though mated
      females showed reduction in evening activity compared to virgins, activity levels
      were not different between polygamous and monogamous females. Although there was
      no detectable effect of mating on clock period, power of the activity/rest rhythm
      was significantly reduced in mated females with no difference seen between
      polygamous and monogamous individuals. These results suggest that courtship
      motivation, represented by evening activity, is successively reduced in males due
      to mating with one or more partners, while in females, it does not depend on the
      number of mating partners. Based on these results we conclude that polygamy
      affects the activity/rest rhythm of fruit flies D. melanogaster in a sex
      dependent manner.

PMID- 25604738
TI  - Ratiometric fluorescence and mesoporous structure dual signal amplification for
      sensitive and selective detection of TNT based on MIP@QD fluorescence sensors.
AB  - Molecularly imprinted polymer coated quantum dot (MIP@QD) fluorescence sensors
      combined with ratiometric fluorescence techniques and mesoporous silica materials
      have been applied to detect TNT for the first time. The assay platform exhibited
      excellent selectivity and sensitivity with a detection limit as low as 15 nM. 

PMID- 25604737
TI  - Morphometric analysis of chameleon fossil fragments from the Early Pliocene of
      South Africa: a new piece of the chamaeleonid history.
AB  - The evolutionary history of chameleons has been predominantly studied through
      phylogenetic approaches as the fossil register of chameleons is limited and
      fragmented. The poor state of preservation of these fossils has moreover led to
      the origin of numerous nomen dubia, and the identification of many chameleon
      fossils remains uncertain. We here examine chameleon fossil fragments from the
      Early Pliocene Varswater formation, exposed at the locality of Langebaanweg "E"
      Quarry along the southwestern coast of South Africa. Our aim was to explore
      whether these fossil fragments could be assigned to extant genera. To do so, we
      used geometric morphometric approaches based on microtomographic imaging of
      extant chameleons as well as the fossil fragments themselves. Our study suggests
      that the fossils from this deposit most likely represent at least two different
      forms that may belong to different genera. Most fragments are phenotypically
      dissimilar from the South African endemic genus Bradypodion and are more similar
      to other chameleon genera such as Trioceros or Kinyongia. However, close phenetic
      similarities between some of the fragments and the Seychelles endemic Archaius or
      the Madagascan genus Furcifer suggest that some of these fragments may not
      contain enough genus-specific information to allow correct identification. Other
      fragments such as the parietal fragments appear to contain more genus-specific
      information, however. Although our data suggest that the fossil diversity of
      chameleons in South Africa was potentially greater than it is today, this remains
      to be verified based on other and more complete fragments. 

PMID- 25604740
TI  - Decreasing sample size in primary prevention studies: A potential role for
      coronary artery calcium score.

PMID- 25604741
TI  - Physical activity, obesity and risk of cardiovascular disease in middle-aged men
      during a median of 30 years of follow-up.
AB  - BACKGROUND: We aimed to investigate associations between combinations of body
      mass index (BMI)-categories, levels of physical activity and long-term risk of
      cardiovascular disease. METHOD AND RESULTS: At age 50 years, cardiovascular risk
      factors were assessed in 2196 participating men of the ULSAM-study. This
      investigation was repeated at age 60, 70, 77 and 82 years. Being physically
      active (PA) was defined as three hours of recreational or hard physical training
      per week. The men were categorized according to BMI/PA-status, as PA/normal
      weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580),
      PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese
      (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and
      physical activity obtained at all examinations. During follow-up (median 30
      years) 850 individuals suffered a cardiovascular disease (myocardial infarction,
      stroke or heart failure). Using updated data on BMI/PA categories, an increased
      risk for cardiovascular disease was seen with increasing BMI, but a high physical
      activity was associated with a lower risk of cardiovascular disease within each
      BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence
      interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non
      PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92)
      and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as
      referent. CONCLUSIONS: Although physical activity was beneficial at all levels of
      BMI regarding the risk of future cardiovascular disease, there was still a
      substantial increased risk associated with being overweight or obese during 30
      years of follow-up.

PMID- 25604739
TI  - Tourette Syndrome: Update.
AB  - Tourette Syndrome is a disorder characterized by tics. It typically begins in
      childhood and often improves in adult life. Tics are best described as voluntary
      movements made automatically so that volition is not ordinarily appreciated.
      There is frequently an urge, sometimes in the form of a specific sensory feeling
      (sensory tic), that precedes the tic. Patients say that they make the tic in
      order to reduce the urge, although shortly after the tic, the urge recurs. The
      sensory feeling may arise due to defective sensory habituation. Since tics
      relieve the urge, this can be considered rewarding, and repetition of this
      behavior may perpetuate the tic as a habit. Tourette Syndrome affects boys more
      than girls and is associated with attention deficit hyperactivity disorder and
      obsessive compulsive disorder. Although Tourette Syndrome often appears to be
      autosomal recessive in inheritance, it has been difficult to find any abnormal
      genes. There is a loss of inhibition in these patients and recent studies show
      abnormalities in brain GABA. Certainly there is also an abnormality in dopamine
      function and dopamine blocking agents are effective therapy. In severe drug
      refractory patients, deep brain stimulation can be effective. 

PMID- 25604742
TI  - Changes in signal molecules and maturation promoting factor levels associate with
      spontaneous resumption of meiosis in rat oocytes.
AB  - The present study was aimed to find out changes in signal molecules and
      maturation promoting factor (MPF) levels during meiotic cell cycle progression
      from diplotene and metaphase-II (M-II) arrest, a period during which oocyte
      achieves meiotic competency. Data suggest that high levels of adenosine 3'-5'
      cyclic monophosphate (cAMP), guanosine 3'-5'-cyclic monophosphate (cGMP), and
      nitric oxide (NO) are associated with diplotene arrest, while reduction in their
      levels correlates with reduced MPF level and meiotic resumption from diplotene
      arrest. On the other hand, increased intracellular NO, calcium (Ca(2+) ) as well
      as hydrogen peroxide (H2 O2 ) levels correlate with decreased cAMP, Thr-161
      phosphorylated cyclin-dependent kinase-1 (Cdk1) as well as cyclin B1 levels. The
      decreased Thr-161 phosphorylated Cdk1 and cyclin B1 level reduce MPF level
      leading to exit from M-II arrest in oocytes cultured in vitro. These data suggest
      that the decrease of cAMP level and increase of cytosolic free Ca(2+) as well as
      H2 O2 levels associate with the reduced MPF level and meiotic resumption from
      diplotene arrest. On the other hand, increase of NO, cGMP, Ca(2+) as well as H2
      O2 levels are associated with reduced MPF and spontaneous exit from M-II arrest
      in rat oocytes cultured in vitro. 

PMID- 25604743
TI  - Influence of provider and urgent care density across different socioeconomic
      strata on outpatient antibiotic prescribing in the USA.
AB  - OBJECTIVES: Despite a strong link between antibiotic use and resistance, and
      highly variable antibiotic consumption rates across the USA, drivers of
      differences in consumption rates are not fully understood. The objective of this
      study was to examine how provider density affects antibiotic prescribing rates
      across socioeconomic groups in the USA. METHODS: We aggregated data on all
      outpatient antibiotic prescriptions filled in retail pharmacies in the USA in
      2000 and 2010 from IMS Health into 3436 geographically distinct hospital service
      areas and combined this with socioeconomic and structural factors that affect
      antibiotic prescribing from the US Census. We then used fixed-effect models to
      estimate the interaction between poverty and the number of physician offices per
      capita (i.e. physician density) and the presence of urgent care and retail
      clinics on antibiotic prescribing rates. RESULTS: We found large geographical
      variation in prescribing, driven in part by the number of physician offices per
      capita. For an increase of one standard deviation in the number of physician
      offices per capita there was a 25.9% increase in prescriptions per capita.
      However, the determinants of the prescription rate were dependent on
      socioeconomic conditions. In poorer areas, clinics substitute for traditional
      physician offices, reducing the impact of physician density. In wealthier areas,
      clinics increase the effect of physician density on the prescribing rate.
      CONCLUSIONS: In areas with higher poverty rates, access to providers drives the
      prescribing rate. However, in wealthier areas, where access is less of a problem,
      a higher density of providers and clinics increases the prescribing rate,
      potentially due to competition.

PMID- 25604744
TI  - Risk factors for acute kidney injury (AKI) in patients treated with polymyxin B
      and influence of AKI on mortality: a multicentre prospective cohort study.
AB  - OBJECTIVES: The objectives of this study were to assess risk factors for acute
      kidney injury (AKI) in patients treated with polymyxin B, a last resort
      antibiotic against Gram-negative bacteria, with a focus on dose, and to determine
      the impact of AKI on mortality of these patients. METHODS: A multicentre
      prospective cohort study was performed including patients >=18 years treated with
      intravenous polymyxin B for >=48 h. The primary outcome was AKI defined by RIFLE
      criteria. Secondary outcomes were 30 day mortality and failure stage of AKI.
      Multivariate analysis with a Cox regression model was performed. The probability
      of developing AKI was determined in a logistic regression model. RESULTS: Four
      hundred-and-ten patients were included. AKI occurred in 189 (46.1%) patients.
      Polymyxin B dose >=150 mg/day was a risk factor for AKI: adjusted HR = 1.95, 95%
      CI = 1.31-2.89, P = 0.01. Higher weight and age were also independently
      associated with AKI. The probability of developing AKI significantly increased
      with doses between 150 and 199 mg/day, regardless of patient weight, with no
      significant increase with higher doses. Higher weight also increased the risk in
      patients receiving the same daily doses. AKI was barely associated with increased
      risk for 30 day mortality (adjusted HR = 1.35, 95% CI = 0.99-1.85, P = 0.06),
      while >=150 mg/day did not increase this risk despite its association with AKI.
      CONCLUSIONS: Polymyxin B total dose is highly related to the risk of AKI,
      regardless of patient weight. Thirty-day mortality tended to be higher in
      patients who developed AKI. The relationship between dose, AKI and mortality must
      be further investigated in studies specifically designed to evaluate this latter
      outcome.

PMID- 25604745
TI  - Rate of cyp51A mutation in Aspergillus fumigatus among lung transplant recipients
      with targeted prophylaxis.
AB  - OBJECTIVES: The most common mechanism of azole (itraconazole and voriconazole)
      resistance in Aspergillus fumigatus is a mutation at the cyp51A locus. The aim of
      our study was to determine the rate of cyp51A mutations in lung transplant
      recipients (LTR) undergoing targeted antifungal prophylaxis with 12 weeks of
      voriconazole. METHODS: We conducted a prospective study that included 22 LTR with
      A. fumigatus between October 2008 and November 2011. Of those, 10 LTR were
      colonized with A. fumigatus and 12 had invasive pulmonary aspergillosis. RESULTS:
      Four patients were found to have A. fumigatus isolates with a cyp51A mutation,
      two had colonization and two had invasive pulmonary aspergillosis. The remaining
      18 LTR had WT cyp51A A. fumigatus isolates. All A. fumigatus isolates (except one
      due to mixed growth) were tested for antifungal susceptibility. A total of nine
      LTR were exposed to azoles prior to A. fumigatus isolation for a median duration
      of 249 (IQR 99-524) days. Azole exposure preceded the isolation of two mutant
      isolates and seven WT isolates. None of the cyp51A mutant isolates conferred
      phenotypic resistance to azoles. CONCLUSIONS: Targeted antifungal prophylaxis in
      LTR did not lead to cyp51A resistance mutations in this cohort. Data on larger
      cohorts who receive universal antifungal prophylaxis are needed.

PMID- 25604746
TI  - Aminoglycoside-modifying enzymes determine the innate susceptibility to
      aminoglycoside antibiotics in rapidly growing mycobacteria.
AB  - OBJECTIVES: Infections caused by the rapidly growing mycobacterium (RGM)
      Mycobacterium abscessus are notoriously difficult to treat due to the innate
      resistance of M. abscessus to most clinically available antimicrobials.
      Aminoglycoside antibiotics (AGA) are a cornerstone of antimicrobial chemotherapy
      against M. abscessus infections, although little is known about intrinsic drug
      resistance mechanisms. We investigated the role of chromosomally encoded putative
      aminoglycoside-modifying enzymes (AME) in AGA susceptibility in M. abscessus.
      METHODS: Clinical isolates of M. abscessus were tested for susceptibility to a
      series of AGA with different substituents at positions 2', 3' and 4' of ring 1 in
      MIC assays. Cell-free extracts of M. abscessus type strain ATCC 19977 and
      Mycobacterium smegmatis strains SZ380 [aac(2')-Id(+)], EP10 [aac(2')-Id(-)] and
      SZ461 [aac(2')-Id(+), rrs A1408G] were investigated for AGA acetylation activity
      using thin-layer chromatography (TLC). Cell-free ribosome translation assays were
      performed to directly study drug-target interaction. RESULTS: Cell-free
      translation assays demonstrated that ribosomes of M. abscessus and M. smegmatis
      show comparable susceptibility to all tested AGA. MIC assays for M. abscessus and
      M. smegmatis, however, consistently showed the lowest MIC values for 2'-hydroxy
      AGA as compared with 2'-amino-AGA, indicating that an aminoglycoside-2'
      acetyltransferase, Aac(2'), contributes to innate AGA susceptibility. TLC
      experiments confirmed enzymatic activity consistent with Aac(2'). Using M.
      smegmatis as a model for RGM, acetyltransferase activity was shown to be up
      regulated in response to AGA-induced inhibition of protein synthesis.
      CONCLUSIONS: Our findings point to AME as important determinants of AGA
      susceptibility in M. abscessus.

PMID- 25604747
TI  - Early ART in primary HIV infection may also preserve lymphopoiesis capability in
      circulating haematopoietic progenitor cells: a case report.

PMID- 25604748
TI  - MicroRNA-19a functions as an oncogenic microRNA in non-small cell lung cancer by
      targeting the suppressor of cytokine signaling 1 and mediating STAT3 activation.
AB  - MicroRNA-19a (miR-19a) has been found to be overexpressed in lung cancers.
      However, the underlying molecular mechanisms of miR-19a in tumorigenesis and the
      development of lung cancer remain poorly understood. In the present study, we
      aimed to delineate the role and mechanisms of action of miR-19a in non-small cell
      lung cancer (NSCLC). miR-19a was found to be overexpressed in both NSCLC tumor
      tissues and cell lines, as shown by RT-PCR. The enforced expression of miR-19a by
      transfection with miR-19a mimics significantly enhanced cell growth and
      viability, cell invasion and the migration of NSCLC cells, as shown by cell
      invasion and migration assays, and promoted the growth of xenograft tumors in a
      mouse xenograft tumor model. Conversely, the inhibition of miR-19a by
      transfection of the cells with miR-19a inhibitor displayed the opposite effects.
      More importantly, we found that miR-19a directly interacted with the 3'
      untranslated region (3'-UTR) of the suppressor of cytokine signaling 1 (SOCS1) by
      dual-luciferase reporter assay. miR-19a was found to be capable of regulating the
      expression of SOCS1 in NSCLC cells. Thus, by modulating SOCS1 expression, miR-19a
      regulated the expression of the signal transducer and activator of transcription
      3 (STAT3). Taken together, our data provide a possible underlying mechanism of
      action of miR-19a in the development of NSCLC and suggest that miR-19a may be a
      novel and promising target for therapeutic intervention in NSCLC.

PMID- 25604749
TI  - Distribution and assessment of marine debris in the deep Tyrrhenian Sea (NW
      Mediterranean Sea, Italy).
AB  - Marine debris is a recognized global ecological concern. Little is known about
      the extent of the problem in the Mediterranean Sea regarding litter distribution
      and its influence on deep rocky habitats. A quantitative assessment of debris
      present in the deep seafloor (30-300 m depth) was carried out in 26 areas off the
      coast of three Italian regions in the Tyrrhenian Sea, using a Remotely Operated
      Vehicle (ROV). The dominant type of debris (89%) was represented by fishing
      gears, mainly lines, while plastic objects were recorded only occasionally.
      Abundant quantities of gears were found on rocky banks in Sicily and Campania
      (0.09-0.12 debris m(-2)), proving intense fishing activity. Fifty-four percent of
      the recorded debris directly impacted benthic organisms, primarily gorgonians,
      followed by black corals and sponges. This work provides a first insight on the
      impact of marine debris in Mediterranean deep ecosystems and a valuable baseline
      for future comparisons.

PMID- 25604750
TI  - Stage of HIV presentation at initial clinic visit following a community-based HIV
      testing campaign in rural Kenya.
AB  - BACKGROUND: The Kenyan Ministry of Health and partners implemented a community
      based integrated prevention campaign (IPC) in Western Kenya in 2008. The aim of
      this study was to determine whether the IPC, compared to Voluntary Counselling
      and Testing (VCT) services, was able to identify HIV positive individuals earlier
      in the clinical course of HIV infection following testing. METHODS: A total of
      1,752 adults aged over 15 years who tested HIV positive through VCT services or
      the IPC, and subsequently registered at initial clinic visit between September
      2008 and September 2010, were considered in the analysis. Multivariable logistic
      regression models were developed to assess the association of CD4 count and WHO
      clinical stage of HIV infection at first clinic appointment with age group,
      gender, marital status and HIV testing source. RESULTS: Male gender and marital
      status were independently associated with late HIV presentation (WHO clinical
      stage 3 or 4 or CD4 count <= 350 cells/MUl) at initial clinic visit. Patients
      testing HIV positive during the IPC had significantly higher mean CD4 count at
      initial clinic visit compared to individuals who tested HIV positive via VCT
      services. Patients testing HIV positive during the IPC had more than two times
      higher odds of presenting early with CD4 count greater than 350 cells/MUl
      (adjusted OR 2.15, 95% CI 1.28 - 3.61, p = 0.004) and presenting early with WHO
      clinical stage 1 or 2 of HIV infection (adjusted OR 2.39, 95% CI 1.24 - 4.60, p =
      0.01) at initial clinic visit compared to individuals who tested HIV positive via
      VCT services. CONCLUSION: The community-based integrated prevention campaign
      identified HIV positive individuals earlier in the course of HIV infection,
      compared to Voluntary Counselling and Testing services. Community-based
      campaigns, such as the IPC, may be able to assist countries to achieve earlier
      testing and initiation of ART in the course of HIV infection. Improving referral
      mechanisms and strengthening linkages between HIV testing and treatment services
      remain a challenge and electronic medical record (EMR) systems may support
      monitoring of patients throughout the HIV care and treatment continuum.

PMID- 25604751
TI  - The unexpected increase of clotrimazole apparent solubility using randomly
      methylated beta-cyclodextrin.
AB  - Clotrimazole (CTZ) and cyclodextrin (CD) inclusion complexes having improved
      apparent water solubility were obtained from phase solubility diagrams. beta-CD
      (1.5% w/w) and hydroxypropyl-beta-CD (40% w/w) offered poor CTZ solubility
      enhancements (12 and 384 times, respectively). Unexpectedly, the apparent
      solubility of CTZ was 9980 times increased from 0.4 ug.mL(-1) (1.42 MUM) without
      CD to 4.89 mg.mL(-1) (14.9 mM) using randomly-methylated beta-CD (Me-beta-CD)
      (40% w/w). This is the highest apparent CTZ solubility improvement ever reported
      in the literature using conventional CDs. Quantitative nuclear magnetic resonance
      ((1) H-NMR) coupled with two-dimensional nuclear Overhauser effect (NOESY)
      experiments and molecular docking calculations showed that the highest
      interactions with Me-beta-CD were reported for CTZ two phenyl groups. A lower
      interaction was reported for chlorophenyl, while imidazole had the weakest
      interaction with Me-beta-CD.

PMID- 25604752
TI  - Determination of the triterpene glycosides in sea cucumbers by liquid
      chromatography with evaporative light scattering and mass spectrometry detection.
AB  - Holothurian triterpene glycosides possess various kinds of biological activities,
      including antifungal, cytotoxic, hemolytic, cytostatic, and immunomodulatory
      effects. In this study, a rapid extraction method of triterpene glycosides from
      sea cucumbers using a small column of C18 solid phase was first developed.
      Furthermore, a novel high-performance liquid chromatography method coupled with
      evaporative light scattering detection and electrospray ionization mass
      spectrometry was established for the determination of each triterpene glycosides
      from different sea cucumbers. Simultaneous separation of all kind of triterpene
      glycoside were achieved on a C18 column. A gradient of aqueous acetonitrile was
      applied, and the method was validated. The liquid chromatography method was
      applied to the online mass detection to identify the triterpene glycosides in the
      purified extraction of eight kinds of pulverized sea cucumber from the market of
      Qingdao, China. The negative mode of [M-H](-)/[M-Na](-) exclusively shown signals
      corresponding to the triterpene glycosides previously reported and the MS(2)
      product ions of those ions indicate the specific structure of each triterpene
      glycoside.

PMID- 25604753
TI  - Atypical abnormal pulmonary vein drainage with atrial septal defect: surgical
      treatment.
AB  - Sinus venosus atrial septal defect (SV-ASD) usually coexists with partial
      anomalous pulmonary vein connection (PAPVC). It is a difficult diagnosis in
      transthoracic echocardiography (TTE) due to eccentric position of defects. We
      present a rare case of atypical anatomical variation in PAPVC, which was never
      described before. Two right pulmonary veins drained into superior vena cava,
      which overrode SV-ASD and interatrial septum, a third pulmonary vein into the
      right atrium. Complete diagnosis could not be set after TTE, nor transesophageal
      echocardiography, whereas angio-CT was finally conclusive. This diagnostic
      approach allowed the surgical planning. 

PMID- 25604754
TI  - Unusual ferromagnetic critical behavior owing to short-range antiferromagnetic
      correlations in antiperovskite Cu(1-x)NMn(3+x) (0.1 <= x <= 0.4).
AB  - For ferromagnets, varying from simple metals to strongly correlated oxides,the
      critical behaviors near the Curie temperature (T(C)) can be grouped into several
      universal classes. In this paper, we report an unusual critical behavior in
      manganese nitrides Cu(1-x)NMn(3+x) (0.1 <= x <= 0.4). Although the critical
      behavior below T(C) can be well described by mean field (MF) theory, robust
      critical fluctuations beyond the expectations of any universal classes are
      observed above T(C) in x = 0.1. The critical fluctuations become weaker when x
      increases, and the MF-like critical behavior is finally restored at x = 0.4. In
      addition, the paramagnetic susceptibility of all the samples deviates from the
      Curie-Weiss (CW) law just above T(C). This deviation is gradually smeared as x
      increases. The short-range antiferromagnetic ordering above T(C) revealed by our
      electron spin resonance measurement explains both the unusual critical behavior
      and the breakdown of the CW law.

PMID- 25604755
TI  - Climate-driven extinctions shape the phylogenetic structure of temperate tree
      floras.
AB  - When taxa go extinct, unique evolutionary history is lost. If extinction is
      selective, and the intrinsic vulnerabilities of taxa show phylogenetic signal,
      more evolutionary history may be lost than expected under random extinction.
      Under what conditions this occurs is insufficiently known. We show that late
      Cenozoic climate change induced phylogenetically selective regional extinction of
      northern temperate trees because of phylogenetic signal in cold tolerance,
      leading to significantly and substantially larger than random losses of
      phylogenetic diversity (PD). The surviving floras in regions that experienced
      stronger extinction are phylogenetically more clustered, indicating that non
      random losses of PD are of increasing concern with increasing extinction
      severity. Using simulations, we show that a simple threshold model of survival
      given a physiological trait with phylogenetic signal reproduces our findings. Our
      results send a strong warning that we may expect future assemblages to be
      phylogenetically and possibly functionally depauperate if anthropogenic climate
      change affects taxa similarly. 

PMID- 25604756
TI  - Perfluorinated and polyfluorinated compounds in lake food webs from the Canadian
      high Arctic.
AB  - Per- and polyfluorinated alkyl substances (PFASs) enter Arctic lakes through long
      range atmospheric transport and local contamination, but their behavior in
      aquatic food webs at high latitudes is poorly understood. This study compared the
      concentrations of perfluorocarboxylates, perfluorosulfonates, and fluorotelomer
      sulfonates (FTS) in biotic and abiotic samples from six high Arctic lakes near
      Resolute Bay, Nunavut, Canada. Two of these lakes are known to be locally
      contaminated by a small airport and Arctic char (Salvelinus alpinus) from these
      lakes had over 100 times higher total [PFAS] when compared to fish from
      neighboring lakes. Perfluorononanoate (PFOA) and perfluorooctanesulfonate (PFOS)
      dominated in char, benthic chironomids (their main prey), and sediments, while
      pelagic zooplankton and water were dominated by lower chain acids and
      perfluorodecanesulfonate (PFDS). This study also provides the first measures of
      perfluoroethylcyclohexanesulfonate (PFECHS) and FTS compounds in water, sediment,
      juvenile char, and benthic invertebrates from lakes in the high Arctic. Negative
      relationships between [PFAS] and delta(15)N values (indicative of trophic
      position) within these food webs indicated no biomagnification. Overall, these
      results suggest that habitat use and local sources of contamination, but not
      trophic level, are important determinants of [PFAS] in biota from freshwater food
      webs in the Canadian Arctic. 

PMID- 25604757
TI  - Innovative community-based vector control interventions for improved dengue and
      Chagas disease prevention in Latin America: introduction to the special issue.

PMID- 25604758
TI  - Innovative community-based ecosystem management for dengue and Chagas disease
      prevention in low and middle income countries in Latin America and the Caribbean.
AB  - In 2009, the WHO Special Programme for Research and Training in Tropical Diseases
      (TDR) and the International Development Research Centre (IDRC) launched a call
      for innovative community-based ecosystem management research projects for dengue
      and Chagas disease prevention in low and middle income countries in Latin America
      and the Caribbean. Eight research institutions were selected. The outputs of
      these projects led to a better understanding of the interaction between
      ecological, biological, social and economic (eco-bio-social) determinants of
      dengue and Chagas disease in Latin America and the Caribbean. Both diseases are
      considered highly relevant in the regional health agendas. 

PMID- 25604760
TI  - Entomological impact and social participation in dengue control: a cluster
      randomized trial in Fortaleza, Brazil.
AB  - BACKGROUND: This study intended to implement a novel intervention strategy, in
      Brazil, using an ecohealth approach and analyse its effectiveness and costs in
      reducing Aedes aegypti vector density as well as its acceptance, feasibility and
      sustainability. The intervention was conducted from 2012 to 2013 in the
      municipality of Fortaleza, northeast Brazil. METHODOLOGY: A cluster randomized
      controlled trial was designed by comparing ten intervention clusters with ten
      control clusters where routine vector control activities were conducted. The
      intervention included: community workshops; community involvement in clean-up
      campaigns; covering the elevated containers and in-house rubbish disposal without
      larviciding; mobilization of schoolchildren and senior inhabitants; and
      distribution of information, education and communication (IEC) materials in the
      community. RESULTS: Differences in terms of social participation, commitment and
      leadership were present in the clusters. The results showed the effectiveness of
      the intervention package in comparison with the routine control programme.
      Differences regarding the costs of the intervention were reasonable and could be
      adopted by public health services. CONCLUSIONS: Embedding social participation
      and environmental management for improved dengue vector control was feasible and
      significantly reduced vector densities. Such a participatory ecohealth approach
      offers a promising alternative to routine vector control measures.

PMID- 25604759
TI  - Eco-bio-social research on community-based approaches for Chagas disease vector
      control in Latin America.
AB  - This article provides an overview of three research projects which designed and
      implemented innovative interventions for Chagas disease vector control in
      Bolivia, Guatemala and Mexico. The research initiative was based on sound
      principles of community-based ecosystem management (ecohealth), integrated vector
      management, and interdisciplinary analysis. The initial situational analysis
      achieved a better understanding of ecological, biological and social determinants
      of domestic infestation. The key factors identified included: housing quality;
      type of peridomestic habitats; presence and abundance of domestic dogs, chickens
      and synanthropic rodents; proximity to public lights; location in the periphery
      of the village. In Bolivia, plastering of mud walls with appropriate local
      materials and regular cleaning of beds and of clothes next to the walls,
      substantially decreased domestic infestation and abundance of the insect vector
      Triatoma infestans. The Guatemalan project revealed close links between house
      infestation by rodents and Triatoma dimidiata, and vector infection with
      Trypanosoma cruzi. A novel community-operated rodent control program
      significantly reduced rodent infestation and bug infection. In Mexico, large
      scale implementation of window screens translated into promising reductions in
      domestic infestation. A multi-pronged approach including community mobilisation
      and empowerment, intersectoral cooperation and adhesion to integrated vector
      management principles may be the key to sustainable vector and disease control in
      the affected regions.

PMID- 25604761
TI  - Long-lasting insecticide-treated house screens and targeted treatment of
      productive breeding-sites for dengue vector control in Acapulco, Mexico.
AB  - BACKGROUND: Long-lasting insecticidal net screens (LLIS) fitted to domestic
      windows and doors in combination with targeted treatment (TT) of the most
      productive Aedes aegypti breeding sites were evaluated for their impact on dengue
      vector indices in a cluster-randomised trial in Mexico between 2011 and 2013.
      METHODS: Sequentially over 2 years, LLIS and TT were deployed in 10 treatment
      clusters (100 houses/cluster) and followed up over 24 months. Cross-sectional
      surveys quantified infestations of adult mosquitoes, immature stages at baseline
      (pre-intervention) and in four post-intervention samples at 6-monthly intervals.
      Identical surveys were carried out in 10 control clusters that received no
      treatment. RESULTS: LLIS clusters had significantly lower infestations compared
      to control clusters at 5 and 12 months after installation, as measured by adult
      (male and female) and pupal-based vector indices. After addition of TT to the
      intervention houses in intervention clusters, indices remained significantly
      lower in the treated clusters until 18 (immature and adult stage indices) and 24
      months (adult indices only) post-intervention. CONCLUSIONS: These safe, simple
      affordable vector control tools were well-accepted by study participants and are
      potentially suitable in many regions at risk from dengue worldwide.

PMID- 25604762
TI  - Effectiveness and feasibility of long-lasting insecticide-treated curtains and
      water container covers for dengue vector control in Colombia: a cluster
      randomised trial.
AB  - BACKGROUND: Long-lasting insecticide-treated net (LLIN) window and door curtains
      alone or in combination with LLIN water container covers were analysed regarding
      effectiveness in reducing dengue vector density, and feasibility of the
      intervention. METHODS: A cluster randomised trial was conducted in an urban area
      of Colombia comparing 10 randomly selected control and 10 intervention clusters.
      In control clusters, routine vector control activities were performed. The
      intervention delivered first, LLIN curtains (from July to August 2013) and
      secondly, water container covers (from October to March 2014). Cross-sectional
      entomological surveys were carried out at baseline (February 2013 to June 2013),
      9 weeks after the first intervention (August to October 2013), and 4-6 weeks
      after the second intervention (March to April 2014). RESULTS: Curtains were
      installed in 922 households and water container covers in 303 households. The
      Breteau index (BI) fell from 14 to 6 in the intervention group and from 8 to 5 in
      the control group. The additional intervention with LLIN covers for water
      containers showed a significant reduction in pupae per person index (PPI)
      (p=0.01). In the intervention group, the PPI index showed a clear decline of 71%
      compared with 25% in the control group. Costs were high but options for cost
      savings were identified. CONCLUSIONS: Short term impact evaluation indicates that
      the intervention package can reduce dengue vector density but sustained effect
      will depend on multiple factors.

PMID- 25604763
TI  - Integrating participatory community mobilization processes to improve dengue
      prevention: an eco-bio-social scaling up of local success in Machala, Ecuador.
AB  - BACKGROUND: This project investigates the effectiveness and feasibility of
      scaling-up an eco-bio-social approach for implementing an integrated community
      based approach for dengue prevention in comparison with existing insecticide
      based and emerging biolarvicide-based programs in an endemic setting in Machala,
      Ecuador. METHODS: An integrated intervention strategy (IIS) for dengue prevention
      (an elementary school-based dengue education program, and clean patio and safe
      container program) was implemented in 10 intervention clusters from November 2012
      to November 2013 using a randomized controlled cluster trial design (20 clusters:
      10 intervention, 10 control; 100 households per cluster with 1986 total
      households). Current existing dengue prevention programs served as the control
      treatment in comparison clusters. Pupa per person index (PPI) is used as the main
      outcome measure. Particular attention was paid to social mobilization and
      empowerment with IIS. RESULTS: Overall, IIS was successful in reducing PPI levels
      in intervention communities versus control clusters, with intervention clusters
      in the six paired clusters that followed the study design experiencing a greater
      reduction of PPI compared to controls (2.2 OR, 95% CI: 1.2 to 4.7). Analysis of
      individual cases demonstrates that consideration for contexualizing programs and
      strategies to local neighborhoods can be very effective in reducing PPI for
      dengue transmission risk reduction. CONCLUSIONS: In the rapidly evolving
      political climate for dengue control in Ecuador, integration of successful social
      mobilization and empowerment strategies with existing and emerging biolarvicide
      based government dengue prevention and control programs is promising in reducing
      PPI and dengue transmission risk in southern coastal communities like Machala.
      However, more profound analysis of social determination of health is called for
      to assess sustainability prospects.

PMID- 25604764
TI  - Improved dengue fever prevention through innovative intervention methods in the
      city of Salto, Uruguay.
AB  - BACKGROUND: Uruguay is located at the southern border of Aedes aegypti
      distribution on the South American sub-continent. The reported dengue cases in
      the country are all imported from surrounding countries. One of the cities at
      higher risk of local dengue transmission is Salto, a border city with heavy
      traffic from dengue endemic areas. METHODS: We completed an intervention study
      using a cluster randomized trial design in 20 randomly selected 'clusters' in
      Salto. The clusters were located in neighborhoods of differing geography and
      economic, cultural and social aspects. RESULTS: Entomological surveys were
      carried out to measure the impact of the intervention on vector densities.
      Through participatory processes of all stakeholders, an appropriate ecosystem
      management intervention was defined. Residents collected the abundant small water
      holding containers and the Ministry of Public Health and the Municipality of
      Salto were responsible for collecting and eliminating them. Additional vector
      breeding places were large water tanks; they were either altered so that they
      could not hold water any more or covered so that oviposition by mosquitoes could
      not take place. CONCLUSIONS: The response from the community and national
      programme managers was encouraging. The intervention evidenced opportunities for
      cost savings and reducing dengue vector densities (although not to statistically
      significant levels). The observed low vector density limits the potential
      reduction due to the intervention. A larger sample size is needed to obtain a
      statistically significant difference.

PMID- 25604765
TI  - An innovative ecohealth intervention for Chagas disease vector control in
      Yucatan, Mexico.
AB  - BACKGROUND: Non-domiciliated (intrusive) triatomine vectors remain a challenge
      for the sustainability of Chagas disease vector control as these triatomines are
      able to transiently (re-)infest houses. One of the best-characterized examples is
      Triatoma dimidiata from the Yucatan peninsula, Mexico, where adult insects
      seasonally infest houses between March and July. METHODS: We focused our study on
      three rural villages in the state of Yucatan, Mexico, in which we performed a
      situation analysis as a first step before the implementation of an ecohealth
      (ecosystem approach to health) vector control intervention. RESULTS: The
      identification of the key determinants affecting the transient invasion of human
      dwellings by T. dimidiata was performed by exploring associations between bug
      presence and qualitative and quantitative variables describing the ecological,
      biological and social context of the communities. We then used a participatory
      action research approach for implementation and evaluation of a control strategy
      based on window insect screens to reduce house infestation by T. dimidiata.
      CONCLUSIONS: This ecohealth approach may represent a valuable alternative to
      vertically-organized insecticide spraying. Further evaluation may confirm that it
      is sustainable and provides effective control (in the sense of limiting
      infestation of human dwellings and vector/human contacts) of intrusive
      triatomines in the region.

PMID- 25604766
TI  - Experimental control of Triatoma infestans in poor rural villages of Bolivia
      through community participation.
AB  - BACKGROUND: Triatoma infestans is the main vector of Chagas disease in the
      southern cone countries. Present control strategies based on indoor and outdoor
      residual insecticide spraying are not sufficient to control disease transmission,
      particularly in Bolivia. Techniques based on the management of the human
      environment may be good alternatives or supplements. METHODS: Social and
      entomological surveys were carried out in four villages of Bolivia situated in
      the dry inter-Andean Valleys and the Chaco region. Risk factors for house
      infestation by T. infestans were identified, and an eco-health intervention based
      on education and community participation was carried out to reduce the risks of
      house infestation. It consisted of implementing simple and low cost vector
      control techniques such as coating of mud walls, cleaning activities and removal
      of poultry that enter rooms to lay eggs. RESULTS: The eco-health intervention
      significantly reduced the number of infested bedrooms, the mean abundance of T.
      infestans in bedrooms and beds, especially in the Chaco region. Mud wall coating
      was well accepted and could be proposed as a supplementary tool to the National
      Program of Chagas Disease Control to enhance the effects of insecticide
      sprayings. CONCLUSIONS: Even if cleaning activities were still neglected,
      community participation proved to be effective in reducing house infestation.

PMID- 25604767
TI  - Development of a community-based intervention for the control of Chagas disease
      based on peridomestic animal management: an eco-bio-social perspective.
AB  - BACKGROUND: Integrated vector management strategies depend on local eco-bio
      social conditions, community participation, political will and inter-sectorial
      partnership. Previously identified risk factors for persistent Triatoma dimidiata
      infestation include the presence of rodents and chickens, tiled roofs, dirt
      floors, partial wall plastering and dog density. METHODS: A community-based
      intervention was developed and implemented based on cyclical stakeholder and
      situational analyses. Intervention implementation and evaluation combined
      participatory action research and cluster randomized pre-test post-test
      experimental designs. The intervention included modified insecticide application,
      education regarding Chagas disease and risk factors, and participatory rodent
      control. RESULTS: At final evaluation there was no significant difference in post
      test triatomine infestation between intervention and control, keeping pre-test
      rodent and triatomine infestations constant. Knowledge levels regarding Chagas
      disease and prevention practices including rodent control, chicken management and
      health service access increased significantly only in intervention communities.
      The odds of nymph infection and rat infestation were 8.3 and 1.9-fold higher in
      control compared to intervention communities, respectively. CONCLUSION: Vector
      control measures without reservoir control are insufficient to reduce
      transmission risk in areas with persistent triatomine infestation. This
      integrated vector management program can complement house improvement initiatives
      by prioritizing households with risk factors such as tiled roofs. Requirement for
      active participation and multi-sectorial coordination poses implementation
      challenges.

PMID- 25604768
TI  - Total colonic aganglionosis and imperforate anus in a severely affected infant
      with Pallister-Hall syndrome.
AB  - Pallister-Hall syndrome is a complex malformation syndrome characterized by a
      wide range of anomalies including hypothalamic hamartoma, polydactyly, bifid
      epiglottis, and genitourinary abnormalities. It is usually caused by truncating
      frameshift/nonsense and splicing mutations in the middle third of GLI3. The
      clinical course ranges from mild to lethal in the neonatal period. We present the
      first patient with Pallister-Hall syndrome reported with total colonic
      aganglionosis, a rare form of Hirschsprung disease with poor long-term outcome.
      The patient also had an imperforate anus, which is the third individual with
      Pallister-Hall syndrome reported with both Hirschsprung disease and an
      imperforate anus. Molecular testing via amniocentesis showed an apparently de
      novo novel nonsense mutation c.2641 C>T (p.Gln881*). His overall medical course
      was difficult and was complicated by respiratory failure and pan-hypopituitarism.
      Invasive care was ultimately withdrawn, and the patient expired at three months
      of age. This patient's phenotype was complex with unusual gastrointestinal
      features ultimately leading to a unfavorable prognosis and outcome, highlighting
      the range of clinical severity in patients with Pallister-Hall syndrome.

PMID- 25604769
TI  - Effect of omega 3 fatty acids plus low-dose aspirin on both clinical and
      biochemical profiles of patients with chronic periodontitis and type 2 diabetes:
      a randomized double blind placebo-controlled study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was, first, to investigate the
      effect of omega 3 (omega3) fatty acids plus low-dose aspirin with closed
      debridement in the treatment of patients with periodontitis and type 2 diabetes
      mellitus (DM), and second, to estimate the expression of monocyte chemoattractant
      protein-3 (MCP-3) in response to the supposed modulatory therapy. MATERIAL AND
      METHODS: Forty patients with chronic periodontitis and type 2 DM were equally
      divided into groups 1 (patients received omega3 plus low-dose aspirin for 6 mo)
      and 2 (patients received placebo during the same period). Evaluation was done
      clinically (pocket depth, clinical attachment loss, gingival index and plaque
      index) and biochemically by estimating levels of interleukin 1beta and MCP-3 in
      gingival crevicular fluid, plus investigating the effect of treatment on glycemic
      control by levels of glycated hemoglobin A1c in serum. All data were collected at
      baseline, 3 and 6 mo after treatment. RESULTS: Subjects of group 1 showed a
      highly significant reduction in pocket depth, clinical attachment loss, gingival
      index (p <= 0.01) after 3 and 6 mo compared to group 2. Glycated hemoglobin A1c
      levels showed a reduction in both groups at the end of the study period, with a
      non-significant difference (p > 0.05). Furthermore, the treatment protocol showed
      a significant reduction in levels of MCP-3 and interleukin 1beta at 3 and 6 mo
      compared to the placebo group. CONCLUSIONS: Within the limits of the present
      study, omega3 plus low-dose aspirin proved effective as an adjunct to closed
      periodontal therapy in the management of patients with periodontitis and type 2
      DM. Moreover, MCP-3 was proven to be effective both in the pathogenesis of the
      disease and as a biomarker in evaluating the response to periodontal treatment.

PMID- 25604771
TI  - Recall dynamics reveal the retrieval of emotional context.
AB  - Memory is often better for emotional rather than neutral stimuli. The benefit for
      emotional items could be the result of an associative mechanism whereby items are
      associated to a slowly updating context. Through this process, emotional features
      are integrated with context during study, and are reactivated during test. The
      presence of emotion in context would both provide a stronger retrieval cue,
      enhancing memory of emotional items, as well as lead to emotional clustering,
      whereby emotionally similar items are recalled consecutively. To measure whether
      associative mechanisms can explain the enhancement for emotional items, we
      conducted a free recall study in which most items were emotionally neutral to
      minimize effects of mood induction and to more closely reflect naturalistic
      settings. We found that emotional items were significantly more likely to be
      recalled than neutral items and that participants were more likely to transition
      between emotional items rather than between emotional and neutral items.
      Together, these results suggest that contextual encoding and retrieval mechanisms
      may drive the benefit for emotional items both within and outside the laboratory.

PMID- 25604770
TI  - Analyzing the most frequent disease loci in targeted patient categories optimizes
      disease gene identification and test accuracy worldwide.
AB  - BACKGROUND: Our genomewide studies support targeted testing the most frequent
      genetic diseases by patient category: (1) pregnant patients, (2) at-risk
      conceptuses, (3) affected children, and (4) abnormal adults. This approach not
      only identifies most reported disease causing sequences accurately, but also
      minimizes incorrectly identified additional disease causing loci. METHODS:
      Diseases were grouped in descending order of occurrence from four data sets: (1)
      GeneTests 534 listed population prevalences, (2) 4129 high risk prenatal
      karyotypes, (3) 1265 affected patient microarrays, and (4) reanalysis of 25,452
      asymptomatic patient results screened prenatally for 108 genetic diseases. These
      most frequent diseases are categorized by transmission: (A) autosomal recessive,
      (B) X-linked, (C) autosomal dominant, (D) microscopic chromosome rearrangements,
      (E) submicroscopic copy number changes, and (F) frequent ethnic diseases.
      RESULTS: Among affected and carrier patients worldwide, most reported mutant
      genes would be identified correctly according to one of four patient categories
      from at-risk couples with <64 tested genes to affected adults with 314 tested
      loci. Three clinically reported patient series confirmed this approach. First,
      only 54 targeted chromosomal sites would have detected all 938 microscopically
      visible unbalanced karyotypes among 4129 karyotyped POC, CVS, and amniocentesis
      samples. Second, 37 of 48 reported aneuploid regions were found among our 1265
      clinical microarrays confirming the locations of 8 schizophrenia loci and 20
      aneuploidies altering intellectual ability, while also identifying 9 of the most
      frequent deletion syndromes. Third, testing 15 frequent genes would have
      identified 124 couples with a 1 in 4 risk of a fetus with a recessive disease
      compared to the 127 couples identified by testing all 108 genes, while testing
      all mutations in 15 genes could have identified more couples. CONCLUSION: Testing
      the most frequent disease causing abnormalities in 1 of 8 reported disease loci
      [~1 of 84 total genes] will identify ~ 7 of 8 reported abnormal Caucasian newborn
      genotypes. This would eliminate ~8 to 10 of ~10 Caucasian newborn gene sequences
      selected as abnormal that are actually normal variants identified when testing
      all ~2500 diseases looking for the remaining 1 of 8 disease causing genes. This
      approach enables more accurate testing within available laboratory and
      reimbursement resources.

PMID- 25604772
TI  - Using electrophysiology to demonstrate that cueing affects long-term memory
      storage over the short term.
AB  - As researchers who study working memory, we often assume that participants keep a
      representation of an object in working memory when we present a cue that
      indicates that the object will be tested in a couple of seconds. This intuitively
      accounts for how well people can remember a cued object, relative to their memory
      for that same object presented without a cue. However, it is possible that this
      superior memory does not purely reflect storage of the cued object in working
      memory. We tested the hypothesis that cues presented during a stream of objects,
      followed by a short retention interval and immediate memory test, can change how
      information is handled by long-term memory. We tested this hypothesis by using a
      family of frontal event-related potentials believed to reflect long-term memory
      storage. We found that these frontal indices of long-term memory were sensitive
      to the task relevance of objects signaled by auditory cues, even when the objects
      repeated frequently, such that proactive interference was high. Our findings
      indicate the problematic nature of assuming process purity in the study of
      working memory, and demonstrate that frequent stimulus repetitions fail to
      isolate the role of working memory mechanisms. 

PMID- 25604773
TI  - Population structure and antimicrobial susceptibility of Pseudomonas aeruginosa
      from animal infections in France.
AB  - BACKGROUND: Pseudomonas aeruginosa is a major human pathogen, which also affects
      animals. It is thought that P. aeruginosa has a non-clonal epidemic population
      structure, with distinct isolates found in humans, animals or the environment.
      However, very little is known about the structure of the P. aeruginosa population
      from diseased animals. Data on antimicrobial resistance are also scarce. RESULTS:
      Thirty-four already registered and 19 new MLST profiles were identified.
      Interestingly, a few clones were more prevalent, and clones associated to human
      outbreaks were also detected. Multidrug resistance phenotypes were overall rare.
      CONCLUSION: We highlight the non clonal structure of the population and show a
      higher prevalence of specific clones, possibly correlating with higher
      pathogenicity. The low proportion of antimicrobial resistance contrasts with the
      high resistance rate of human isolates.

PMID- 25604774
TI  - The view of European experts regarding health economics for medical nutrition in
      disease-related malnutrition.
AB  - Health-care systems are currently facing tremendous budget constraints resulting
      in growing pressure on decision makers and health-care providers to obtain the
      maximum possible health benefits of the resources available. Choices have to be
      made, and health economics can help in allocating limited health-care resources
      among unlimited wants and needs. Attempts to achieve cost reductions often focus
      on severe pathologies and chronic diseases as they commonly represent high health
      care expenditures. In this context, awareness of the considerable financial
      burden caused by disease-related malnutrition (DRM) is lacking. Possibilities of
      reducing costs by optimising the management of DRM through medical nutrition will
      mostly not even be taken into account. During a European expert meeting, the
      total evaluation of medical nutrition was viewed and discussed. The aim of this
      meeting was to gain an experts' outline of the key issues relating to the health
      economic assessment of the use of medical nutrition. This article provides a
      summary of the observations per discussed item and describes the next steps
      suggested. 

PMID- 25604775
TI  - Ethnic-specific cut-points for sarcopenia: evidence from black South African
      women.
AB  - BACKGROUND/OBJECTIVES: Age-related muscle and fat mass (FM) changes are ethnicity
      specific. We aimed to develop a cut-point for the muscle mass component of
      sarcopenia for black South African (SA) women, and to assess its predictive
      value, in comparison to established cut-points, to identify functional ability
      among older black SA women. SUBJECTS/METHODS: In a cross-sectional study, a
      sarcopenia cut-point was calculated from dual energy X-ray absorptiometry (DXA)
      derived appendicular skeletal muscle mass (ASM) indexes (ASMI) from two young
      black SA reference groups. The new cut-point was compared with the most recent
      Foundation for the National Institutes of Health (FNIH) criteria (ASM <15.02 kg;
      and ASM(BMI) <0.512), an internationally accepted cut-point (ASMI <5.5 kg/m(2))
      and a residual method adjusting for FM. All cut-points were then applied to 221
      older black women to predict gait speed and handgrip strength. RESULTS: A cut
      point of ASMI <4.94 kg/m(2) was derived from the young SA reference groups. Using
      this cut-point, 9.1% of older women were classified as sarcopenic, compared with
      16.7-38.7% using other cut-points. The only cut-points that significantly
      predicted low functional ability (low gait speed and low handgrip strength) in
      older black women were the new SA cut-point and the FNIH ASM criterion.
      Multivariate logistic regression models for both these cut-points significantly
      predicted low handgrip strength (odds ratio (OR)=3.71, P=0.007 and OR=3.42,
      P=0.001, respectively) and low gait speed (OR=9.82, P=0.004 and OR=8.71, P=0.008,
      respectively). CONCLUSIONS: The new SA cut-point had similar or greater odds of
      predicting reduced functional ability in older SA women when compared with other
      internationally accepted cut-points.

PMID- 25604776
TI  - 24-h Void number as an indicator of hydration status.
AB  - BACKGROUND/OBJECTIVES: Few user-friendly hydration assessment techniques exist
      for the general population to use on a daily basis. The present study evaluated
      void number over 24 h as a potential hydration assessment tool. SUBJECTS/METHODS:
      Male and female subjects collected urine for 24 h while adequately hydrated
      (n=44; 22 +/- 4 years, 168 +/- 16 cm, 73 +/- 15 kg) or fluid restricted (n=43; 22
      +/- 3 years, 175 +/- 10 cm, 81 +/- 24 kg). As a control, participants were asked
      to void when feeling the 'first urge to void' on a commonly used urge scale and
      noted the volume of each void. For each sample, 24-h urine volume, osmolality
      (U(OSM)), specific gravity (U(SG)) and color were measured in the laboratory.
      RESULTS: As designed, the level of urge upon voiding was consistent throughout
      the study (2 +/- 0; 'first urge to void'). Samples were classified by U(SG) as
      either euhydrated (U(SG)<1.020) or hypohydrated (U(SG) ? 1.020). Grouping by
      U(OSM) did not change results. Euhydrated versus hypohydrated individuals had
      greater 24-h urine volume (1933 +/- 864 versus 967 +/- 306 ml, respectively) and
      lower urine color (2 +/- 1 versus 5 +/- 1), U(SG) (1.012 +/- 0.004 versus 1.025
      +/- 0.004) and UOSM (457 +/- 180 versus 874 +/- 175 mOsm/kg H2O; all P<0.001).
      Euhydrated individuals voided more than hypohydrated individuals over the 24-h
      period (5 +/- 2 versus 3 +/- 1 voids; P<0.001). Additionally, void number
      inversely correlated with hydration status as identified by U(SG) (r=-0.50;
      P<0.05) and U(OSM) (r=-0.56; P<0.05). CONCLUSIONS: In conclusion, over 24 h,
      individuals with a higher void number were euhydrated (that is, had less
      concentrated hydration biomarkers) than those with a lower void number. Based on
      these data, void number might be utilized as a simple and feasible hydration
      assessment for the general public, as it utilizes no equipment or technical
      expertise.

PMID- 25604777
TI  - Response to: 'Methylcobalamine is effective in peripheral neuropathies'.

PMID- 25604778
TI  - Does food store access modify associations between intrapersonal factors and
      fruit and vegetable consumption?
AB  - BACKGROUND/OBJECTIVES: Existing theoretical frameworks suggest that healthy
      eating is facilitated by an individual's ability, motivation and environmental
      opportunities. It is plausible, although largely untested, that the importance of
      factors related to ability and motivation differ under varied environmental
      conditions. This study aimed to determine whether the magnitude of associations
      between fruit and vegetable consumption and intrapersonal factors (ability and
      motivation) were modified by differences in access to stores selling these items
      (environmental opportunities). SUBJECTS/METHODS: Cross-sectional analysis of 4335
      women from socioeconomically disadvantaged neighbourhoods in the state of
      Victoria, Australia. Self-reported fruit and vegetable consumption was assessed
      against a number of ability- and motivation-related factors. To examine whether
      associations were modified by store access, interactions with access to
      supermarkets and greengrocers within 2 km of participants' households were
      tested. RESULTS: Of the two factors related to ability and seven factors related
      to motivation, almost all were associated with fruit and vegetable consumption.
      In general, associations were not modified by store access suggesting that these
      factors were not tempered by environmental opportunities. CONCLUSIONS: This study
      provides little support for the hypothesis that the importance of intra-personal
      factors to fruit and vegetable consumption is modified by food store access.
      Further research on this topic is required to inform behaviour change
      interventions.

PMID- 25604779
TI  - Compliance with preoperative oral nutritional supplements in patients at
      nutritional risk--only a question of will?
AB  - BACKGROUND/OBJECTIVES: Preoperative nutrition has been shown to reduce morbidity
      after major gastrointestinal (GI) surgery in selected patients at risk. In a
      randomized trial performed recently (NCT00512213), almost half of the patients,
      however, did not consume the recommended dose of nutritional intervention. The
      present study aimed to identify the risk factors for noncompliance.
      SUBJECTS/METHODS: Demographic (n = 5) and nutritional (n = 21) parameters for
      this retrospective analysis were obtained from a prospectively maintained
      database. The outcome of interest was compliance with the allocated intervention
      (ingestion of ? 11/15 preoperative oral nutritional supplement units). Uni- and
      multivariate analyses of potential risk factors for noncompliance were performed.
      RESULTS: The final analysis included 141 patients with complete data sets for the
      purpose of the study. Fifty-nine patients (42%) were considered noncompliant.
      Univariate analysis identified low C-reactive protein levels (P = 0.015),
      decreased recent food intake (P = 0.032) and, as a trend, low hemoglobin (P =
      0.065) and low pre-albumin (P = 0.056) levels as risk factors for decreased
      compliance. However, none of them was retained as an independent risk factor
      after multivariate analysis. Interestingly, 17 potential explanatory parameters,
      such as upper GI cancer, weight loss, reduced appetite or co-morbidities, did not
      show any significant correlation with reduced intake of nutritional supplements.
      CONCLUSIONS: Reduced compliance with preoperative nutritional interventions
      remains a major issue because the expected benefit depends on the actual intake.
      Seemingly, obvious reasons could not be retained as valid explanations.
      Compliance seems thus to be primarily a question of will and information; the
      importance of nutritional supplementation needs to be emphasized by specific
      patients' education.

PMID- 25604780
TI  - Microsomal transfer protein inhibitors, new approach for treatment of familial
      hypercholesterolemia, review of the literature, original findings, and clinical
      significance.
AB  - The genetic causes of cholesterol metabolism disorders usually lead to premature
      atherosclerosis. The most well recognized genetically caused hypercholesterolemia
      is familial hypercholesterolemia. Although the disease is well known, as the
      discovery of low-density lipoprotein receptor, the classical treatment with lipid
      lowering drugs (statins, fibrates, ezetimibe, colesevelam) is still not adequate
      and new options are seeking. This review is an attempt to analyze the microsomal
      transfer protein (MTP) inhibitors as a new approach for treatment of familial
      hypercholesterolemia, to reviews the literature according to MTP inhibitors and
      finally to provide original findings. 

PMID- 25604782
TI  - The Millennium Development Goals: taking stock as the first phase ends.

PMID- 25604781
TI  - Hyperbaric Oxygen Preconditioning Attenuates Myocardium Ischemia-Reperfusion
      Injury Through Upregulation of Heme Oxygenase 1 Expression: PI3K/Akt/Nrf2 Pathway
      Involved.
AB  - BACKGROUND: With the rise of the burden of ischemic heart disease, both clinical
      and economic evidence show a desperate need to protect the heart against
      myocardium ischemia-reperfusion injury-related complications following cardiac
      surgery or percutaneous coronary intervention. However, there is no effective
      intervention for myocardium ischemia-reperfusion injury as yet. METHODS: We
      pretreated mice with 4 daily 2.0 absolute atmosphere (ATA) hyperbaric oxygen,
      then observed its effects on heart function parameters and infarct size following
      in situ ischemia-reperfusion. Multiple oxidative and inflammation products were
      measured in the myocardium. Next, we investigated the expression of heme
      oxygenase 1 (HO-1), phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein
      kinase (Akt) pathway, and NF-E2-related factor 2 (Nrf2) in the presence of
      myocardium ischemia-reperfusion injury, hyperbaric oxygen preconditioning, and
      their inhibitors and their effects on heart function parameters. RESULTS:
      Hyperbaric oxygen preconditioning ameliorated the cardiac function and
      histological alterations induced by myocardium ischemia-reperfusion injury,
      decreased oxidative products and proinflammatory cytokine. Hyperbaric oxygen
      preconditioning increased expression of HO-1, which was suppressed by PI3K
      inhibitor LY294002, Nrf2 knockout, and Akt inhibitor triciribine. The expression
      of Nrf2 was enhanced by hyperbaric oxygen preconditioning, but decreased by
      LY294002 and triciribine. The Akt was also activated by hyperbaric oxygen
      preconditioning but suppressed by LY294002. The hemodynamic assays showed that
      cardiac function was suppressed by LY294002, Nrf2 knockout, and triciribine.
      CONCLUSION: These data present a novel signaling mechanism by which hyperbaric
      oxygen preconditioning protects myocardium ischemia-reperfusion injury via
      PI3K/Akt/Nrf2-dependent antioxidant defensive system.

PMID- 25604784
TI  - Effect of cryopreservation on the sperm DNA fragmentation dynamics of the
      bottlenose dolphin (Tursiops truncatus).
AB  - Sperm DNA fragmentation is one of the major causes of infertility; the sperm
      chromatin dispersion test (SCDt) evaluates this parameter and offers the
      advantage of species-specific validated protocol and ease of use under field
      conditions. The main purpose of this study was to evaluate sperm DNA
      fragmentation dynamics in both fresh and post-thaw bottlenose dolphin sperm using
      the SCDt following different cryopreservation protocols to gain new information
      about the post-thaw differential sperm DNA longevity in this species. Fresh and
      cryopreserved semen samples from five bottlenose dolphins were examined for sperm
      DNA fragmentation dynamics using the SCDt (Halomax((r))). Sperm DNA fragmentation
      was assessed immediately at collection and following cryopreservation (T0) and
      then after 0.5, 1, 4, 8, 24, 48 and 72 h incubation at 37 degrees C. Serially
      collected ejaculates from four dolphins were frozen using different
      cryopreservation protocols in a TES-TRIS-fructose buffer (TTF), an egg-yolk-free
      vegetable lipid LP1 buffer (LP1) and human sperm preservation medium (HSPM).
      Fresh ejaculated spermatozoa initially showed low levels of DNA fragmentation for
      up to 48 h. Lower Sperm DNA fragmentation (SDF) was found in the second fresh
      ejaculate compared to the first when more than one sample was collected on the
      same day (p < 0.05); this difference was not apparent in any other seminal
      characteristic. While there was no difference observed in SDF between fresh and
      frozen-thawed sperm using the different cryopreservation protocols immediately
      after thawing (T0), frozen-thawed spermatozoa incubated at 37 degrees C showed an
      increase in the rate of SDF after 24 h. Sperm frozen in the LP1((p)) buffer had
      higher levels (p < 0.05) of DNA fragmentation after 24- and 48-h incubation than
      those frozen in TTF or HSPM. No correlation was found between any seminal
      characteristic and DNA fragmentation in either fresh and/or frozen-thawed
      samples.

PMID- 25604785
TI  - Inter-aromatic distances in Geobacter sulfurreducens pili relevant to biofilm
      charge transport.

PMID- 25604786
TI  - Degradation products of the extracellular pathogen Streptococcus pneumoniae
      access the cytosol via its pore-forming toxin.
AB  - Streptococcus pneumoniae is a leading pathogen with an extracellular lifestyle;
      however, it is detected by cytosolic surveillance systems of macrophages. The
      innate immune response that follows cytosolic sensing of cell wall components
      results in recruitment of additional macrophages, which subsequently clear
      colonizing organisms from host airways. In this study, we monitored cytosolic
      access by following the transit of the abundant bacterial surface component
      capsular polysaccharide, which is linked to the cell wall. Confocal and electron
      microscopy visually characterized the location of cell wall components in murine
      macrophages outside membrane-bound organelles. Quantification of capsular
      polysaccharide through cellular fractionation demonstrated that cytosolic access
      of bacterial cell wall components is dependent on phagocytosis, bacterial
      sensitivity to the host's degradative enzyme lysozyme, and release of the pore
      forming toxin pneumolysin. Activation of p38 mitogen-activated protein kinase
      (MAPK) signaling is important for limiting access to the cytosol; however,
      ultimately, these are catastrophic events for both the bacteria and the
      macrophage, which undergoes cell death. Our results show how expression of a pore
      forming toxin ensures the death of phagocytes that take up the organism, although
      cytosolic sensing results in innate immune detection that eventually allows for
      successful host defense. These findings provide an example of how cytosolic
      access applies to an extracellular microbe and contributes to its pathogenesis.
      IMPORTANCE: Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen
      that is a leading cause of pneumonia. Pneumococcal disease is preceded by
      colonization of the nasopharynx, which lasts several weeks before being cleared
      by the host's immune system. Although S. pneumoniae is an extracellular microbe,
      intracellular detection of pneumococcal components is critical for bacterial
      clearance. In this study, we show that following bacterial uptake and degradation
      by phagocytes, pneumococcal products access the host cell cytosol via its pore
      forming toxin. This phenomenon of cytosolic access results in phagocyte death and
      may serve to combat the host cells responsible for clearing the organism. Our
      results provide an example of how intracellular access and subsequent immune
      detection occurs during infection with an extracellular pathogen.

PMID- 25604787
TI  - Evaluation of the potential impact of Ebola virus genomic drift on the efficacy
      of sequence-based candidate therapeutics.
AB  - Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that
      caused disease among small populations with extraordinarily high lethality. At
      the end of 2013, EBOV initiated an unprecedented disease outbreak in West Africa
      that is still ongoing and has already caused thousands of deaths. Recent studies
      revealed the genomic changes this particular EBOV variant undergoes over time
      during human-to-human transmission. Here we highlight the genomic changes that
      might negatively impact the efficacy of currently available EBOV sequence-based
      candidate therapeutics, such as small interfering RNAs (siRNAs),
      phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the
      observed mutations modify the sequence of the binding sites of monoclonal
      antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35
      targets and might influence the binding efficacy of the sequence-based
      therapeutics, suggesting that their efficacy should be reevaluated against the
      currently circulating strain.

PMID- 25604788
TI  - Application of a neutral community model to assess structuring of the human lung
      microbiome.
AB  - DNA from phylogenetically diverse microbes is routinely recovered from healthy
      human lungs and used to define the lung microbiome. The proportion of this DNA
      originating from microbes adapted to the lungs, as opposed to microbes dispersing
      to the lungs from other body sites and the atmosphere, is not known. We use a
      neutral model of community ecology to distinguish members of the lung microbiome
      whose presence is consistent with dispersal from other body sites and those that
      deviate from the model, suggesting a competitive advantage to these microbes in
      the lungs. We find that the composition of the healthy lung microbiome is
      consistent with predictions of the neutral model, reflecting the overriding role
      of dispersal of microbes from the oral cavity in shaping the microbial community
      in healthy lungs. In contrast, the microbiome of diseased lungs was readily
      distinguished as being under active selection. We also assessed the viability of
      microbes from lung samples by cultivation with a variety of media and incubation
      conditions. Bacteria recovered by cultivation from healthy lungs represented
      species that comprised 61% of the 16S rRNA-encoding gene sequences derived from
      bronchoalveolar lavage samples. IMPORTANCE: Neutral distribution of microbes is a
      distinguishing feature of the microbiome in healthy lungs, wherein constant
      dispersal of bacteria from the oral cavity overrides differential growth of
      bacteria. No bacterial species consistently deviated from the model predictions
      in healthy lungs, although representatives of many of the dispersed species were
      readily cultivated. In contrast, bacterial populations in diseased lungs were
      identified as being under active selection. Quantification of the relative
      importance of selection and neutral processes such as dispersal in shaping the
      healthy lung microbiome is a first step toward understanding its impacts on host
      health.

PMID- 25604789
TI  - RovS and its associated signaling peptide form a cell-to-cell communication
      system required for Streptococcus agalactiae pathogenesis.
AB  - Bacteria can communicate with each other to coordinate their biological functions
      at the population level. In a previous study, we described a cell-to-cell
      communication system in streptococci that involves a transcriptional regulator
      belonging to the Rgg family and short hydrophobic peptides (SHPs) that act as
      signaling molecules. Streptococcus agalactiae, an opportunistic pathogenic
      bacterium responsible for fatal infections in neonates and immunocompromised
      adults, has one copy of the shp/rgg locus. The SHP-associated Rgg is called RovS
      in S. agalactiae. In this study, we found that the SHP/RovS cell-to-cell
      communication system is active in the strain NEM316 of S. agalactiae, and we
      identified different partners that are involved in this system, such as the Eep
      peptidase, the PptAB, and the OppA1-F oligopeptide transporters. We also
      identified a new target gene controlled by this system and reexamined the
      regulation of a previously proposed target gene, fbsA, in the context of the SHP
      associated RovS system. Furthermore, our results are the first to indicate the
      SHP/RovS system specificity to host liver and spleen using a murine model, which
      demonstrates its implication in streptococci virulence. Finally, we observed that
      SHP/RovS regulation influences S. agalactiae's ability to adhere to and invade
      HepG2 hepatic cells. Hence, the SHP/RovS cell-to-cell communication system
      appears to be an essential mechanism that regulates pathogenicity in S.
      agalactiae and represents an attractive target for the development of new
      therapeutic strategies. IMPORTANCE: Rgg regulators and their cognate pheromones,
      called small hydrophobic peptides (SHPs), are present in nearly all streptococcal
      species. The general pathways of the cell-to-cell communication system in which
      Rgg and SHP take part are well understood. However, many other players remain
      unidentified, and the direct targets of the system, as well as its link to
      virulence, remain unclear. Here, we identified the different players involved in
      the SHP/Rgg system in S. agalactiae, which is the leading agent of severe
      infections in human newborns. We have identified a direct target of the Rgg
      regulator in S. agalactiae (called RovS) and examined a previously proposed
      target, all in the context of associated SHP. For the first time, we have also
      demonstrated the implication of the SHP/RovS mechanism in virulence, as well as
      its host organ specificity. Thus, this cell-to-cell communication system may
      represent a future target for S. agalactiae disease treatment.

PMID- 25604790
TI  - Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using
      cerebrospinal fluid.
AB  - Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in
      assessing patient care options and transmission risks. Real-time quaking-induced
      conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing
      specimens are valuable in distinguishing CJD from non-CJD conditions but have
      required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which
      identified positive CSF samples within 4 to 14 h with better analytical
      sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were
      RT-QuIC positive using the previous conditions, 10 were positive using the new
      assay. In these and further analyses, a total of 46 of 48 CSF samples from
      sporadic CJD patients were positive, while all 39 non-CJD patients were negative,
      giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation
      RT-QuIC assay markedly improved the speed and sensitivity of detecting prion
      seeds in CSF specimens from CJD patients. This should enhance prospects for rapid
      and accurate ante mortem CJD diagnosis. IMPORTANCE: A long-standing problem in
      dealing with various neurodegenerative protein misfolding diseases is early and
      accurate diagnosis. This issue is particularly important with human prion
      diseases, such as CJD, because prions are deadly, transmissible, and unusually
      resistant to decontamination. The recently developed RT-QuIC test allows for
      highly sensitive and specific detection of CJD in human cerebrospinal fluid and
      is being broadly implemented as a key diagnostic tool. However, as currently
      applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we
      have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD
      patients can be discriminated in a matter of hours rather than days with enhanced
      sensitivity. These improvements should allow for much faster, more accurate, and
      practical testing for CJD. In broader terms, our study provides a prototype for
      tests for misfolded protein aggregates that cause many important amyloid
      diseases, such as Alzheimer's, Parkinson's, and tauopathies.

PMID- 25604791
TI  - Correction for Sandai et al., The Evolutionary Rewiring of Ubiquitination Targets
      Has Reprogrammed the Regulation of Carbon Assimilation in the Pathogenic Yeast
      Candida albicans.

PMID- 25604792
TI  - Malaria induces anemia through CD8+ T cell-dependent parasite clearance and
      erythrocyte removal in the spleen.
AB  - Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected
      and uninfected erythrocytes and is a frequent fatal complication. It is
      proportional not to circulating parasitemia but total parasite mass (sequestered)
      in the organs. Thus, immune responses that clear parasites in organs may trigger
      changes leading to anemia. Here, we use an outbred-rat model where increasing
      parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic
      parasite clearance was associated with activated CD8(+) T cells, immunodepletion
      of which prevented parasite clearance. CD8(+) T cell repletion and concomitant
      reduction of the parasite load was associated with exacerbated (40 to 60%)
      hemoglobin loss and changes in properties of uninfected erythrocytes. Together,
      these data suggest that CD8(+) T cell-dependent parasite clearance causes
      erythrocyte removal in the spleen and thus anemia. In children infected with the
      human malaria parasite Plasmodium falciparum, elevation of parasite biomass (not
      the number of circulating parasites) increased the odds ratio for SMA by 3.5-fold
      (95% confidence intervals [CI95%], 1.8- to 7.5-fold). CD8(+) T cell
      expansion/activation independently increased the odds ratio by 2.4-fold (CI95%,
      1.0- to 5.7-fold). Concomitant increases in both conferred a 7-fold (CI95%, 1.9-
      to 27.4-fold)-greater risk for SMA. Together, these data suggest that CD8(+)
      dependent parasite clearance may predispose individuals to uninfected-erythrocyte
      loss and SMA, thus informing severe disease diagnosis and strategies for vaccine
      development. IMPORTANCE: Malaria is a major global health problem. Severe malaria
      anemia (SMA) is a complex disease associated with partial immunity. Rapid
      hemoglobin reductions of 20 to 50% are commonly observed and must be rescued by
      transfusion (which can carry a risk of HIV acquisition). The causes and risk
      factors of SMA remain poorly understood. Recent studies suggest that SMA is
      linked to parasite biomass sequestered in organs. This led us to investigate
      whether immune mechanisms that clear parasites in organs trigger anemia. In rats,
      erythropoiesis is largely restricted to the bone marrow, and critical aspects of
      the spleen expected to be important in anemia are similar to those in humans.
      Therefore, using a rat model, we show that severe anemia is caused through CD8(+)
      T cell-dependent parasite clearance and erythrocyte removal in the spleen. CD8
      activation may also be a new risk factor for SMA in African children.

PMID- 25604793
TI  - Is the debate and "pause" on experiments that alter pathogens with pandemic
      potential influencing future plans of graduate students and postdoctoral fellows?

PMID- 25604794
TI  - The impact of cancer prevention guideline adherence on overall mortality in a
      high-risk cohort of women from the New York site of the Breast Cancer Family
      Registry.
AB  - The American Cancer Society (ACS) recommends at least 150 min of moderate
      intensity physical activity per week, alcohol intake of <=1 drink per day, and
      maintaining a body mass index (BMI) of <25 kg/m(2) for breast cancer prevention.
      Adherence to these guidelines has been linked to lower overall mortality in
      average-risk populations, it is not known if mortality reduction extends to women
      at higher risk given their family history of breast cancer. We followed 2,905
      women from a high-risk Breast Cancer Family Registry in New York, of which 77 %
      were white non-Hispanic and 23 % were Hispanic. We collected information on BMI,
      physical activity, and alcohol intake at baseline and prospectively followed our
      cohort for outcomes based on questionnaires and National Death Index linkage. We
      used Cox regression to examine the relation between adherence to ACS guidelines
      and overall mortality and examined effect modification by race, age, and BRCA
      status. There were 312 deaths after an average of 9.2 +/- 4.1 years of follow-up.
      Adherence to all three ACS recommendations was associated with 44-53 % lower
      mortality in women unaffected with breast cancer at baseline [Hazard Ratio (HR)
      0.56, 95 % CI (0.33-0.93)] and in women affected with breast cancer at baseline
      [HR 0.47, 95 % CI (0.30-0.74)]. These associations remained after stratification
      by age, race, and BRCA status {e.g., BRCA1 and/or BRCA2 carriers [HR 0.39, 95 %
      CI (0.16-0.97)]}. These results support that women at high risk, similar to women
      at average risk, may also have substantial benefits from maintaining the ACS
      guidelines.

PMID- 25604797
TI  - Invasive lobular carcinoma of the breast: local recurrence after breast
      conserving therapy by subtype approximation and surgical margin.
AB  - Invasive lobular carcinoma (ILC) typically presents at a later stage than
      invasive ductal carcinoma (IDC) and poses unique radiographic and surgical
      challenges. However, current principles of breast-conserving therapy (BCT) do not
      distinguish between histologic subtypes, raising uncertainty about the optimal
      approach for patients with ILC. We studied 998 BCT patients from 1998-2007,
      comprised 74 % IDC, 8 % ILC, and 18 % with mixed ILC/IDC. In light of recent
      guidelines addressing surgical margins, specimens were assessed for margin width
      and biologic subtype. The Kaplan-Meier method and Cox proportional hazards models
      were used to analyze effects of patient and disease characteristics on local
      recurrence (LR). At a median of 119 months, 45 patients had an isolated LR. 10
      year LR was 5.5 % for patients with IDC, 4.4 % for ILC, and 1.2 % for mixed
      histology (p = 0.08). The majority of ILC cases had luminal A biologic subtype
      (91.1 %), and analysis among all luminal A cases revealed 10-year LR of 2.6 % for
      IDC, 3.4 % for ILC, and 0 % for mixed tumors (p = 0.12). Patients with ILC were
      more likely to have initially positive surgical margins (45.0 vs 17.5 %; p <
      0.001) resulting in more frequent re-excision (57.1 % vs 40.4 %; p = 0.02),
      though final margins were similar between ILC and IDC (p = 0.88). No LR was
      observed among ILC or mixed histology patients with margins <2 mm (n = 28). On
      multivariate analysis, histologic subtype was not associated with LR (p = 0.52).
      Modern approaches confer similarly favorable LR rates for ILC, IDC, and mixed
      histology breast cancers despite inherent histologic differences. Patients with
      ILC did not require more extensive surgical margins than those with IDC.

PMID- 25604798
TI  - Ruthenium(II) polypyridyl complexes as dual inhibitors of telomerase and
      topoisomerase.
AB  - One novel ruthenium polypyridyl complex, [Ru(bpy)2(icip)](2+) (1), and two
      previously reported ruthenium polypyridyl complexes, [Ru(bpy)2(pdppz)](2+) ()2
      and [Ru(bpy)2(tactp)](2+) (3) (bpy = 2,2'-bipyridine, icip = 2-(indeno[2,1
      b]chromen-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, pdppz = phenanthro[4,5
      abc]dipyrido[3,2-h:2',3'-j]phenazine, tactp = 4,5,9,18-tetraazachryseno[9,10-b]
      triphenylene), have been synthesised. As expected, these complexes show
      inhibition towards telomerase by inducing and stabilising the G-quadruplex
      structure, and behave as topoisomerase I/II poisons at the same time.
      Additionally, the acute and chronic cytotoxicities of the complexes are
      considered. Furthermore, cell apoptosis experiments are used to briefly study the
      mechanism. Because studies involving multi-target inhibition towards
      topoisomerase and telomerase of Ru(II) complexes have not been reported
      previously, the present research may help to develop innovative chemical
      strategies and therapies.

PMID- 25604799
TI  - Size-exclusion HPLC provides a simple, rapid, and versatile alternative method
      for quality control of vaccines by characterizing the assembly of antigens.
AB  - The assembly of antigen structure is often crucial to the potency of vaccines.
      Currently adopted methods like animal testing and ultracentrifugation take long
      time and are difficult to automate for multiple samples. Here we develop a size
      exclusion high-performance liquid chromatography (SE-HPLC) method to characterize
      the assembly of antigen structure during both manufacturing process and storage.
      Three important vaccine antigens including inactivated foot and mouth disease
      virus (FMDV), which is a virus vaccine; and two virus-like particles (VLPs)
      vaccines involving hepatitis B core antigen (HBcAg) VLPs, and hepatitis B surface
      antigen (HBsAg) VLPs, were successfully analyzed using commercially available TSK
      gel columns with pore size above 45nm. Combined with other analytical methods
      including SDS-PAGE, dynamic light scattering, wavelength scan, and multi-angle
      laser light scattering, the SE-HPLC method was proven to be a simple, rapid, and
      reliable tool for antigen particles assembly analysis. Specifically, for FMDV
      whole virus particle, SE-HPLC was used to analyze 146S content in vaccine
      preparations and the thermal dissociation of the 146S. For HBcAg-VLPs that are
      expressed in recombinant Escherichia coli, its expression level during cell
      culture process was quantitatively monitored by SE-HPLC. The SE-HPLC also showed
      applicability for quality check of HBsAg vaccine preparations by monitoring the
      product consistency of different lot number and the product stability during
      storage. Results shown in this work clearly demonstrated that SE-HPLC method has
      potential as a versatile alternative technology for control of the final product
      by both manufacturers and the regulatory agencies. 

PMID- 25604800
TI  - Impact of influenza vaccination on mortality in the French elderly population
      during the 2000-2009 period.
AB  - With declining influenza vaccine coverage in the elderly in recent years in
      France, we aimed at assessing the benefits of seasonal influenza vaccination,
      based on available data for observed mortality, vaccine coverage and vaccine
      effectiveness. To estimate the annual number of deaths avoided by vaccination in
      the people aged 65 years or more, we used the following three elements: an
      estimate of vaccine effectiveness against all-cause mortality (based on the
      "difference-in-differences" approach which reduces the usual bias seen in
      observational studies), French mortality data and vaccine coverage data. We
      estimated an annual average of 2000 deaths currently avoided through vaccination
      and a vaccine effectiveness of 35% against influenza-attributable deaths. Around
      2650 vaccinations are needed to prevent a death among the elderly. Communicating
      these results should help restoring at-risk populations' confidence in influenza
      vaccination. 

PMID- 25604801
TI  - An H10N8 influenza virus vaccine strain and mouse challenge model based on the
      human isolate A/Jiangxi-Donghu/346/13.
AB  - Three human cases of H10N8 viruses were reported in China in late 2013 and early
      2014, two of which were fatal. This was the first time the H10N8 subtype has been
      detected in humans and no vaccine candidates or antibody therapy has been
      developed for these viruses so far. We developed an H10N8 vaccine candidate virus
      based on A/Jiangxi-Donghu/346/13 that can also be used in a murine challenge
      model for vaccine and monoclonal antibody research. The vaccine virus is a 6:2 re
      assortant virus expressing the surface glycoproteins of A/Jiangxi-Donghu/346/13
      on an A/Puerto Rico/8/34 backbone. Vaccination with inactivated challenge virus
      or recombinant hemagglutinin or neuraminidase derived from this strain protected
      mice from viral challenge. 

PMID- 25604802
TI  - Early investigational drugs targeting PPAR-alpha for the treatment of metabolic
      disease.
AB  - INTRODUCTION: The fibrates have been used for many years to treat dyslipidemias
      and have also recently been shown to have anti-inflammatory effects. They are
      relatively weak PPAR-alpha agonists and do have some adverse effects. Novel
      compounds are in development, which are selective PPAR modulators (SPPARMs) and
      have more potent PPAR-alpha agonist activity. These may prove to have advantages
      in the treatment of dyslipidemia, insulin resistance and non-alcoholic fatty
      liver disease (NAFLD). AREAS COVERED: This review focuses on PPAR-alpha agonists
      or SPPARMs in development describing the preclinical and early clinical studies.
      The information was obtained by searching the published literature and abstracts
      from recent meetings. Ongoing clinical trials were identified using the
      Clinicaltrial.gov database. EXPERT OPINION: There is still a need for new drugs
      to treat atherogenic dyslipidemia. The highly potent and selective PPAR-alpha
      agonist K-877 has shown beneficial effects on atherogenic dyslipidemia and
      absence of some adverse effects seen with fibrates. The dual PPAR-alpha/PPAR
      delta agonist GFT-505 has shown favorable results in improving atherogenic
      dyslipidemia and insulin resistance and appears to be a potential candidate for
      the treatment of NAFLD. Long-term trials are needed to assess the safety and
      efficacy of these new agents for cardiovascular and liver outcomes.

PMID- 25604803
TI  - Role of the osmolyte taurine on the folding of a model protein, hen egg white
      lysozyme, under a crowding condition.
AB  - Taurine is one of the osmolytes that maintain the structure of proteins in cells
      exposed to denaturing environmental stressors. Recently, cryoelectron tomographic
      analysis of eukaryotic cells has revealed that their cytoplasms are crowded with
      proteins. Such crowding conditions would be expected to hinder the efficient
      folding of nascent polypeptide chains. Therefore, we examined the role of taurine
      on the folding of denatured and reduced lysozyme, as a model protein, under a
      crowding condition. The results confirmed that taurine had a better effect on
      protein folding than did beta-alanine, which has a similar chemical structure,
      when the protein to be folded was present at submillimolar concentration. NMR
      analyses further revealed that under the crowding condition, taurine had more
      interactions than did beta-alanine with the lysozyme molecule in both the folded
      and denatured states. We concluded that taurine improves the folding of the
      reduced lysozyme at submillimolar concentration to allow it to interact more
      favorably with the lysozyme molecule. Thus, the role of taurine, as an osmolyte
      in vivo, may be to assist in the efficient folding of proteins.

PMID- 25604804
TI  - Training Program for Cardiology Residents to Perform Focused Cardiac Ultrasound
      Examination with Portable Device.
AB  - INTRODUCTION: Training requirements for general cardiologists without
      echocardiographic expertise to perform focused cardiac ultrasound (FCU) with
      portable devices have not yet been defined. The objective of this study was to
      evaluate a training program to instruct cardiology residents to perform FCU with
      a hand-carried device (HCD) in different clinical settings. METHODS: Twelve
      cardiology residents were subjected to a 50-question test, 4 lectures on basic
      echocardiography and imaging interpretation, the supervised interpretation of 50
      echocardiograms and performance of 30 exams using HCD. After this period, they
      repeated the written test and were administered a practical test comprising 30
      exams each (360 patients) in different clinical settings. They reported on 15
      parameters and a final diagnosis; their findings were compared to the HCD exam of
      a specialist in echocardiography. RESULTS: The proportion of correct answers on
      the theoretical test was higher after training (86%) than before (51%; P =
      0.001). The agreement was substantial among the 15 parameters analyzed (kappa
      ranging from 0.615 to 0.891; P < 0.001). The percentage of correct interpretation
      was lower for abnormal (75%) than normal (95%) items, for valve abnormalities
      (85%) compared to other items (92%) and for graded scale (87%) than for
      dichotomous (95%) items (P < 0.0001, for all). For the final diagnoses, the kappa
      value was higher than 0.941 (P < 0.001; 95% CI [0.914, 0.955]). CONCLUSION: The
      training proposed enabled residents to perform FCU with HCD, and their findings
      were in good agreement with those of a cardiologist specialized in
      echocardiography.

PMID- 25604805
TI  - Stress distribution in delayed replanted teeth splinted with different
      orthodontic wires: a three-dimensional finite element analysis.
AB  - AIM: The aim was to evaluate the biomechanical behavior of the supporting bony
      structures of replanted teeth and the periodontal ligament (PDL) of adjacent
      teeth when orthodontic wires with different mechanical properties are applied,
      with three-dimensional finite element analysis. MATERIALS AND METHODS: Based on
      tomographic and microtomographic data, a three-dimensional model of the anterior
      maxilla with the corresponding teeth (tooth 13-tooth 23) was generated to
      simulate avulsion and replantation of the tooth 21. The teeth were splinted with
      orthodontic wire (O 0.8 mm) and composite resin. The elastic modulus of the three
      orthodontic wires used, that is, steel wire (FA), titanium-molybdenum wire (FTM),
      and nitinol wire (FN) were 200 GPa, 84 GPa, and 52 GPa, respectively. An oblique
      load (100 N) was applied at an angle of 45 degrees  on the incisal edge of the
      replanted tooth and was analyzed using Ansys Workbench software. The maximum
      (sigmamax) and minimum (sigmamin) principal stresses generated in the PDL,
      cortical and alveolar bones, and the modified von Mises (sigmavM) values for the
      orthodontic wires were obtained. RESULTS: With regard to the cortical bone and
      PDL, the highest sigmamin and sigmamax values for FTM, FN, and FA were checked.
      With regard to the alveolar bone, sigmamax and sigmamin values were highest for
      FA, followed by FTM and FN. The sigmavM values of the orthodontic wires followed
      the order of rigidity of the alloys, that is, FA > FTM > FN. CONCLUSION: The
      biomechanical behavior of the analyzed structures with regard to all the three
      patterns of flexibility was similar.

PMID- 25604806
TI  - Information entropy as a measure of genetic diversity and evolvability in
      colonization.
AB  - In recent years, several studies have examined the relationship between genetic
      diversity and establishment success in colonizing species. Many of these studies
      have shown that genetic diversity enhances establishment success. There are
      several hypotheses that might explain this pattern, and here I focus on the
      possibility that greater genetic diversity results in greater evolvability during
      colonization. Evaluating the importance of this mechanism first requires that we
      quantify evolvability. Currently, most measures of evolvability have been
      developed for quantitative traits whereas many studies of colonization success
      deal with discrete molecular markers or phenotypes. The purpose of this study is
      to derive a suitable measure of evolvability for such discrete data. I show that
      under certain assumptions, Shannon's information entropy of the allelic
      distribution provides a natural measure of evolvability. This helps to alleviate
      previous concerns about the interpretation of information entropy for genetic
      data. I also suggest that information entropy provides a natural generalization
      to previous measures of evolvability for quantitative traits when the trait
      distributions are not necessarily multivariate normal. 

PMID- 25604807
TI  - Causes of death in men with localized prostate cancer: a nationwide, population
      based study.
AB  - OBJECTIVE: To detail the distribution of causes of death from localized prostate
      cancer (PCa). PATIENTS AND METHODS: The database PCBase Sweden links the Swedish
      National Prostate Cancer Register with other nationwide population-based
      healthcare registers. We selected all 57 187 men diagnosed with localized PCa
      between 1997 and 2009 and their 114 374 PCa-free control subjects, matched
      according to age and county of residence. Mortality was calculated using
      competing risk regression analyses, taking into account PCa risk category, age
      and Charlson comorbidity index (CCI). RESULTS: In men with low-risk PCa, all
      cause mortality was lower compared with that in corresponding PCa-free men: 10
      year all-cause mortality was 18% for men diagnosed at age 70 years, with a CCI
      score of 0, and 21% among corresponding control subjects. Of these cases, 31%
      died from cardiovascular disease (CVD) compared with 37% of the corresponding
      control subjects. For men with low-risk PCa, 10-year PCa-mortality was 0.4, 1 and
      3% when diagnosed at age 50, 60 and 70 years, respectively. PCa was the third
      most common cause of death (18%), after CVD (31%) and other cancers (30%). By
      contrast, PCa was the most common cause of death in men with intermediate- and
      high-risk localized PCa. CONCLUSIONS: Men with low-risk PCa had lower all-cause
      mortality than PCa-free men because of lower CVD mortality, driven by early
      detection selection; however, for men with intermediate- or high-risk disease,
      the rate of PCa death was substantial, irrespective of CCI score, and this was
      even more pronounced for those diagnosed at age 50 or 60 years.

PMID- 25604809
TI  - Attention problems in children with epilepsy. How is the long-term outcome?
AB  - INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) is one of the most
      common childhood disorders and frequently seen in other conditions like epilepsy
      as well. The prevalence of ADHD in the general paediatric population is estimated
      at 3-6% persisting into adulthood in up to one third of persons affected. The
      prevalence of ADHD in epilepsy is understood to be significantly higher.
      Approximately one third of children with epilepsy do also have a diagnosis of
      ADHD. How these attention problems develop over the years is however not clear.
      We therefore evaluated the severity of attention problems in children with
      epilepsy at late childhood and assessed it again in adolescence. Data was being
      compared with attention problems of children with developmental ADHD. METHOD: 16
      boys with diagnosed combined idiopathic epilepsy/ADHD and 14 boys with
      developmental ADHD were investigated twice; at a mean age of 10.94 (SD = 1.63)
      and then again at a mean age of 15.82 (SD = 2.0). At the baseline examination all
      patients completed Raven's Progressive Matrices to assess intelligence. To
      measure symptom severity of ADHD, parents were asked to complete the short
      version of the Conner's Rating Scale for Parents at both times. Parents of
      children with combined epilepsy/ADHD furthermore gave information about seizure
      frequency and intake of anticonvulsants. RESULTS: Patient groups did not
      significantly differ in age and IQ. Results of the baseline examination revealed
      elevated scores in both patient groups for the Conner's Rating Scales; ADHD
      group: M = 16.86 (SD = 5.35); Epilepsy/ADHD group: M = 14.77 (SD = 4.76) but no
      differences between the groups (p = .29; z = .39). Qualitatively, patients with
      developmental ADHD showed more abnormalities in the area of
      hyperactivity/impulsivity while patients with epilepsy/ADHD had more problems
      with inattention. Results of the follow-up examination showed a significant
      reduction of symptoms in the ADHD group of minus 4.23 points; M = 12.63 (SD =
      3.89) (p = .02); The reduction in the epilepsy/ADHD group was even bigger with
      minus 6.77 points; M = 8.00 (SD = 6.46) (p = .03). However, difference between
      the two groups reached no significance (p = .079; z = 1.19). None of the patients
      with epilepsy has had seizures in the meantime. CONCLUSION: We found a
      significant reduction of ADHD symptoms in our patients from the time of late
      childhood to adolescence. That symptoms of ADHD, especially hyperactivity, lessen
      with age is known from the literature (Biedermann et al., 2010). We found the
      same data for patients with idiopathic epilepsy and ADHD. Over the same period of
      time problems of attention improved substantially. We conclude that development
      and brain maturation may have a similar positive effect on attention problems in
      children with epilepsy than in developmental ADHD.

PMID- 25604808
TI  - The diagnostic pathway in complex paediatric neurology: a cost analysis.
AB  - BACKGROUND: The diagnostic trajectory of complex paediatric neurology may be
      long, burdensome, and expensive while its diagnostic yield is frequently modest.
      Improvement in this trajectory is desirable and might be achieved by innovations
      such as whole exome sequencing. In order to explore the consequences of
      implementing them, it is important to map the current pathway. To that end, this
      study assessed the healthcare resource use and associated costs in this
      diagnostic trajectory in the Netherlands. METHODS: Fifty patients presenting with
      complex paediatric neurological disorders of a suspected genetic origin were
      included between September 2011 and March 2012. Data on their healthcare resource
      utilization were collected from the hospital medical charts. Unit prices were
      obtained from the Dutch Healthcare Authority, the Dutch Healthcare Insurance
      Board, and the financial administration of the hospital. Bootstrap simulations
      were performed to determine mean quantities and costs. RESULTS: The mean duration
      of the diagnostic trajectory was 40 months. A diagnosis was established in 6% of
      the patients. On average, patients made 16 physician visits, underwent four
      imaging and two neurophysiologic tests, and had eight genetic and 16 other tests.
      Mean bootstrapped costs per patient amounted to ?12,475, of which 43% was for
      genetic tests (?5,321) and 25% for hospital visits (?3,112). CONCLUSION:
      Currently, the diagnostic trajectories of paediatric patients who have complex
      neurological disease with a strong suspected genetic component are lengthy,
      resource-intensive, and low-yield. The data from this study provide a backdrop
      against which the introduction of novel techniques such as whole exome sequencing
      should be evaluated.

PMID- 25604810
TI  - Wet-chemical synthesis of phase-pure FeOF nanorods as high-capacity cathodes for
      sodium-ion batteries.
AB  - It is challenging to prepare phase-pure FeOF by wet-chemical methods.
      Furthermore, nanostructured FeOF has never been reported. In this study,
      hierarchical FeOF nanorods were synthesized through a facile, one-step, wet
      chemical method by the use of just FeF3?3H2O and an alcohol. It was possible to
      significantly control the FeOF nanostructure by the selection of alcohols with an
      appropriate molecular structure. A mechanism for the formation of the nanorods is
      proposed. An impressive high specific capacity of approximately 250 mAh g(-1) and
      excellent cycling and rate performances were demonstrated for sodium storage. The
      hierarchical FeOF nanorods are promising high-capacity cathodes for SIBs.

PMID- 25604811
TI  - Development, implementation, and initial evaluation of a foundational open
      interoperability standard for oncology treatment planning and summarization.
AB  - OBJECTIVE: Develop and evaluate a foundational oncology-specific standard for the
      communication and coordination of care throughout the cancer journey, with early
      stage breast cancer as the use case. MATERIALS AND METHODS: Owing to broad uptake
      of the Health Level Seven (HL7) Consolidated Clinical Document Architecture (C
      CDA) by health information exchanges and large provider organizations, we
      developed an implementation guide in congruence with C-CDA. The resultant product
      was balloted through the HL7 process and subsequently implemented by two groups:
      the Health Story Project (Health Story) and the Athena Breast Health Network
      (Athena). RESULTS: The HL7 Implementation Guide for CDA, Release 2: Clinical
      Oncology Treatment Plan and Summary, DSTU Release 1 (eCOTPS) was successfully
      balloted and published as a Draft Standard for Trial Use (DSTU) in October 2013.
      Health Story successfully implemented the eCOTPS the 2014 meeting of the
      Healthcare Information and Management Systems Society (HIMSS) in a clinical
      vignette. During the evaluation and implementation of eCOPS, Athena identified
      two practical concerns: (1) the need for additional CDA templates specific to
      their use case; (2) the many-to-many mapping of Athena-defined data elements to
      eCOTPS. DISCUSSION: Early implementation of eCOTPS has demonstrated successful
      vendor-agnostic transmission of oncology-specific data. The modularity enabled by
      the C-CDA framework ensures the relatively straightforward expansion of the
      eCOTPS to include other cancer subtypes. Lessons learned during the process will
      strengthen future versions of the standard. CONCLUSION: eCOTPS is the first
      oncology-specific CDA standard to achieve HL7 DSTU status. Oncology standards
      will improve care throughout the cancer journey by allowing the efficient
      transmission of reliable, meaningful, and current clinical data between the many
      involved stakeholders.

PMID- 25604812
TI  - The Effect of Platelet and Desmopressin Administration on Early Radiographic
      Progression of Traumatic Intracranial Hemorrhage.
AB  - Limited data exist regarding the use of hemostatic adjuncts on the progression of
      traumatic intracranial hemorrhage (tICH). The objective of this study was to
      examine the impact of platelet transfusion and desmopressin (DDAVP)
      administration on hemorrhage progression following tICH. We hypothesized that
      platelet and DDAVP administration would not result in decreased early hemorrhagic
      progression. We performed a three-year retrospective analysis of a Level 1 trauma
      center database to identify all adult patents with blunt tICH. The primary
      outcome was early (<=4 hours) radiographic hemorrhagic progression. Secondary
      outcomes included mortality, frequency of operative interventions, and
      complications. Multiple logistic regression analysis was performed to identify
      predictors for hemorrhage progression and mortality. A propensity score analysis
      also was performed to minimize differences and improve comparability between
      patients who received platelets and DDAVP and those who did not. Of 408 patients
      with tICH meeting the inclusion criteria, 126 received platelets and DDAVP (P/D
      [+]) and 282 did not (P/D [-]). Overall, 37% of patients demonstrated early
      radiographic hemorrhage progression. On univariate analysis, there was no
      difference in the incidence of hemorrhage progression between groups (43.7% [P/D
      (+)] vs. 34.2% [P/D (-)]; p = 0.07). On multivariate analyses, platelet and DDAVP
      administration was not associated with either a decreased risk of hemorrhage
      progression (odds ratio [OR] = 1.40, confidence interval [CI] = 0.80-2.40; p =
      0.2) or mortality (OR = 1.50, CI = 0.60-4.30; p = 0.4). The administration of
      platelets and DDAVP is not associated with a decreased risk for early
      radiographic hemorrhage progression in patients with tICH. Further prospective
      study of these potentially hemostatic adjuncts in patients with tICH is
      potentially warranted.

PMID- 25604813
TI  - Human Islet Morphology Revisited: Human and Rodent Islets Are Not So Different
      After All.
AB  - There has been great interest in understanding how human islets differ from
      rodent islets. Three major issues about human islet morphology have remained
      controversial over recent decades: 1) the proportion of the islet made up of beta
      cells; 2) whether islet cell types have a non-random mantle-core pattern, as seen
      in rodents, or are randomly scattered throughout the islet; 3) the relation of
      the different cell types to the blood vessels within the islet, which has
      implications for intraislet function. We re-examined these issues on
      immunostained sections of non-diabetic adult human pancreas. The composition of
      the islets can vary by the analysis method (number vs volume) and by the sampling
      of islets by size. The majority of adult human islets have clear, non-random
      clustering of beta-cells and blood vessels that penetrate into the beta-cell
      cores. We conclude that although there is far more variability in islet
      composition both within each human pancreas and among different human pancreas
      than in rodent pancreas, the islet architecture is not so different between the
      species. The intrapancreatic variability raises important questions about how
      islets evolve and function throughout life and how this might relate to the
      pathogenesis of diabetes.

PMID- 25604815
TI  - CRTAP mutation in a patient with Cole-Carpenter syndrome.
AB  - In 1987, Cole and Carpenter reported two unrelated infants with multiple
      fractures and deformities of bone, with a skeletal phenotype similar to severe
      osteogenesis imperfecta. In addition, these patients also had proptosis, blue
      sclerae, hydrocephalus, and a distinct facial gestalt. They were reported to be
      of normal intelligence. Radiologically, these patients had characteristic
      skeletal manifestations including craniosynostosis and deformities similar to
      severe progressive osteogenesis imperfecta. Since the first description, there
      have only been a few other reports of patients with a similar phenotype. Collagen
      studies performed in reported patients have been normal. The molecular basis of
      this syndrome has not been elucidated and the inheritance pattern is still
      unknown. We report on a child with Cole-Carpenter syndrome phenotype who has a
      homozygous c.118G>T mutation in exon 1 of the CRTAP gene. We describe the
      clinical features and correlate this with her molecular results. This is the
      first report towards elucidating the molecular basis of Cole-Carpenter syndrome.

PMID- 25604814
TI  - Validation of normal human bronchial epithelial cells as a model for influenza A
      infections in human distal trachea.
AB  - Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the
      distal-most aspect of the trachea at the bifurcation, have been used for a number
      of studies in respiratory disease research. Differences between the source tissue
      and the differentiated primary cells may impact infection studies based on this
      model. Therefore, we examined how well-differentiated NHBE cells compared with
      their source tissue, the human distal trachea, as well as the ramifications of
      these differences on influenza A viral pathogenesis research using this model. We
      employed a histological analysis including morphological measurements, electron
      microscopy, multi-label immunofluorescence confocal microscopy, lectin
      histochemistry, and microarray expression analysis to compare differentiated
      NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height,
      cell type variety and distribution varied significantly. Electron microscopy
      confirmed differences in cellular attachment and paracellular junctions.
      Influenza receptor lectin histochemistry revealed that alpha2,3 sialic acids were
      rarely present on the apical aspect of the differentiated NHBE cells, but were
      present in low numbers in the distal trachea. We bound fluorochrome bioconjugated
      virus to respiratory tissue and NHBE cells and infected NHBE cells with human
      influenza A viruses. Both indicated that the pattern of infection progression in
      these cells correlated with autopsy studies of fatal cases from the 2009
      pandemic.

PMID- 25604816
TI  - Sample preparation methods for determination of drugs of abuse in hair samples: A
      review.
AB  - Hair analysis has assumed increasing importance in the determination of
      substances of abuse, both in clinical and forensic toxicology investigations.
      Hair analysis offers particular advantages over other biological matrices (blood
      and urine), including a larger window of detection, ease of collection and sample
      stability. In the present work, an overview of sample preparation techniques for
      the determination of substances of abuse in hair is provided, specifically
      regarding the principal steps in hair sample treatment-decontamination,
      extraction and purification. For this purpose, a survey of publications found in
      the MEDLINE database from 2000 to date was conducted. The most widely consumed
      substances of abuse and psychotropic drugs were considered. Trends in
      simplification of hair sample preparation, washing procedures and cleanup methods
      are discussed. Alternative sample extraction techniques, such as head-space solid
      phase microextraction (HS-SPDE), supercritical fluid extraction (SFE) and
      molecularly imprinted polymers (MIP) are also reported. 

PMID- 25604817
TI  - OPLS in batch monitoring - Opens up new opportunities.
AB  - In batch statistical process control (BSPC), data from a number of "good" batches
      are used to model the evolution (trajectory) of the process and they also define
      model control limits, against which new batches may be compared. The benchmark
      methods used in BSPC include partial least squares (PLS) and principal component
      analysis (PCA). In this paper, we have used orthogonal projections to latent
      structures (OPLS) in BSPC and compared the results with PLS and PCA. The
      experimental study used was a batch hydrogenation reaction of nitrobenzene to
      aniline characterized by both UV spectroscopy and process data. The key idea is
      that OPLS is able to separate the variation in data that is correlated to the
      process evolution (also known as 'batch maturity index') from the variation that
      is uncorrelated to process evolution. This separation of different types of
      variations can generate different batch trajectories and hence lead to different
      established model control limits to detect process deviations. The results
      demonstrate that OPLS was able to detect all process deviations and provided a
      good process understanding of the root causes for these deviations. PCA and PLS
      on the other hand were shown to provide different interpretations for several of
      these process deviations, or in some cases they were unable to detect actual
      process deviations. Hence, the use of OPLS in BSPC can lead to better fault
      detection and root cause analysis as compared to existing benchmark methods and
      may therefore be used to complement the existing toolbox. 

PMID- 25604819
TI  - A sheath flow gating interface for the on-line coupling of solid-phase extraction
      with capillary electrophoresis.
AB  - A sheath flow gating interface (SFGI) is presented for the on-line coupling of
      solid-phase extraction (SPE) with capillary electrophoresis (CE). The design,
      construction and operation of the SFGI are described in detail. After operating
      conditions were investigated and selected, the SFGI was evaluated on a SPE-CE-UV
      setup using hydroxylated poly(glycidyl methacrylate-co-ethylene dimethacrylate)
      monolith as the absorbent and using three phenols as the test analytes. The
      preconcentration factors obtained with the SPE-CE-UV system and the SPE-UV part
      are 530 and 550, respectively. The plate numbers obtained using the SPE-CE-UV
      system are slightly better than or comparable to those with the CE-UV part. The
      precisions (RSDs) of 100 consecutive injections are 2.43%, 3.86%, and 4.25% for
      peak height, peak area and migration time, respectively. The measured recoveries
      for the river water samples spiked at three different levels are in the range of
      93.6-102.8% with the interday RSD values ranging from 2.0 to 4.5% (n=3). These
      data collectively demonstrate that the SFGI has the ability to exactly and
      reproducibly transfer nanoliters of fractions from SPE onto CE with no
      degradation of the efficiencies of SPE and CE, suggesting a great potential to be
      routinely used for the coupling of SPE, microcolumn LC or FIA with CE. 

PMID- 25604818
TI  - Droplet electrochemical study of the pH dependent redox behavior of novel
      ferrocenyl-carborane derivatives and its application in specific cancer cell
      recognition.
AB  - Novel ferrocenyl based carboranes (FcCBs) and their distinguish behavior for
      cancer cell recognition have been explored in this contribution. The voltammetric
      study in a droplet of 10MUL placed on the surface of a glassy carbon electrode
      demonstrates the excellent electrochemical behavior of FcCBs, which could be
      further exploited for establishing the promising and sensitive biosensors. The
      FcCBs' redox behavior is examined in a wide pH range, and square wave voltammetry
      revealed the reversible and irreversible nature of first and second anodic peaks.
      The obvious shifts in peak potentials corresponding with the change of pH values
      demonstrate the abstraction of electrons to be accompanied with the transfer of
      protons. By using the droplet electrochemical technique, FcCBs can be employed to
      distinguish normal and cancer cells with a linear range from 1.0*10(3) to
      3.0*10(4)cells mL(-1) and the limit of detection at 800cells mL(-1). The novel
      carborane derivatives could be utilized as important potential molecular probes
      for specific recognition of cancer cells like leukemia cells from normal cells.

PMID- 25604820
TI  - Gold nanoparticle-antibody conjugates for specific extraction and subsequent
      analysis by liquid chromatography-tandem mass spectrometry of malondialdehyde
      modified low density lipoprotein as biomarker for cardiovascular risk.
AB  - Oxidized low-density lipoproteins (OxLDLs) like malondialdehyde-modified low
      density lipoprotein (MDA-LDL) play a major role in atherosclerosis and have been
      proposed as useful biomarkers for oxidative stress. In this study, gold
      nanoparticles (GNPs) were functionalized via distinct chemistries with anti-MDA
      LDL antibodies (Abs) for selective recognition and capture of MDA-LDL from
      biological matrices. The study focused on optimization of binding affinities and
      saturation capacities of the antiMDA-LDL-Ab-GNP bioconjugate by exploring
      distinct random and oriented immobilization approaches, such as (i) direct
      adsorptive attachment of Abs on the GNP surface, (ii) covalent bonding by amide
      coupling of Abs to carboxy-terminated-pegylated GNPs, (iii) oriented
      immobilization via oxidized carbohydrate moiety of the Ab on hydrazide
      derivatized GNPs and (iv) cysteine-tagged protein A (cProtA)-bonded GNPs.
      Depending on immobilization chemistry, up to 3 antibodies per GNP could be
      immobilized as determined by ELISA. The highest binding capacity was achieved
      with the GNP-cProtA-Ab bioconjugate which yielded a saturation capacity of 2.24+/
      0.04MUgmL(-1) GNP suspension for MDA-LDL with an affinity Kd of 5.25+/-0.11*10(
      10)M. The GNP-cProtA-antiMDA-LDL bioconjugate revealed high specificity for MDA
      LDL over copper(II)-oxidized LDL as well as native human LDL. This clearly
      demonstrates the usefulness of the new GNP-Ab bioconjugates for specific
      extraction of MDA-LDL from plasma samples as biomarkers of oxidative stress.
      Their combination as specific immunoextraction nanomaterials with analysis by LC
      MS/MS allows sensitive and selective detection of MDA-LDL in complex samples. 

PMID- 25604821
TI  - Tween 20-stabilized gold nanoparticles combined with adenosine triphosphate
      BODIPY conjugates for the fluorescence detection of adenosine with more than 1000
      fold selectivity.
AB  - This study describes the development of a simple, enzyme-free, label-free,
      sensitive, and selective system for detecting adenosine based on the use of Tween
      20-stabilized gold nanoparticles (Tween 20-AuNPs) as an efficient fluorescence
      quencher for boron dipyrromethene-conjugated adenosine 5'-triphosphate (BODIPY
      ATP) and as a recognition element for adenosine. BODIPY-ATP can interact with
      Tween 20-AuNPs through the coordination between the adenine group of BODIPY-ATP
      and Au atoms on the NP surface, thereby causing the fluorescence quenching of
      BODIPY-ATP through the nanometal surface energy transfer (NSET) effect. When
      adenosine attaches to the NP surface, the attached adenosine exhibits additional
      electrostatic attraction to BODIPY-ATP. As a result, the presence of adenosine
      enhances the efficiency of AuNPs in fluorescence quenching of BODIPY-ATP. The
      AuNP-induced fluorescence quenching of BODIPY-ATP progressively increased with an
      increase in the concentration of adenosine; the detection limit at a signal-to
      noise ratio of 3 for adenosine was determined to be 60nM. The selectivity of the
      proposed system was more than 1000-fold for adenosine over any adenosine analogs
      and other nucleotides. The proposed system combined with a phenylboronic acid
      containing column was successfully applied to the determination of adenosine in
      urine. 

PMID- 25604822
TI  - Construction of a peptide with an electroactive daunomycin like a pendant arm to
      detect ovalbumin.
AB  - In this study, a peptide-1 (RNRCKGTDVQAW) constructing lysozyme was conjugated
      with an electroactive daunomycin in order to voltammetrically detect ovalbumin
      (OVA). Hetero-bifunctional cross-linking agents with four kinds of ethylene
      chains in differing lengths were used to bind the peptide-1 and daunomycin. After
      a cross-linking agent had reacted with an amino group of daunomycin, the compound
      was introduced into the peptide to the cysteine residue in the peptide using a
      pendant arm. The OVA was sensed via a change in the electrode response of the
      daunomycin moiety, based on the binding between the peptide and the OVA. The
      adsorption of the peptide probe on the electrode increased with increases in the
      ethylene chain. The binding constants between the peptide probes and the OVA,
      however, did not depend on the length of the chain. This was because the ethylene
      chain influenced the binding. When the peptide and the daunomycin were bound
      using N-(6-maleimidocaproyloxy) sulfosuccinimide, the electrode response of the
      peptide probe was the most sensitive from among the four cross-linking agents.
      The calibration curve of the OVA using the peptide probe was linear and ranged
      from 1.5*10(-11) to 3.0*10(-10)M. Furthermore, this method could be applied to
      the electrochemical sensing of the OVA in egg whites and in fetal bovine serum. 

PMID- 25604823
TI  - i-Motif-modulated fluorescence detection of silver(I) with an ultrahigh
      specificity.
AB  - A novel Ag(+) sensor has been designed based on the mechanism that i-motif
      formation induced by Ag(+) was sensitively recognized by a cyanine dye. The
      sensor exhibited an over 130-16,000 fold selectivity toward Ag(+) than that
      toward other metal ions. This research not only provides a step forward toward
      the development of Ag(+) detection but also represents a new application for i
      motif DNA. 

PMID- 25604824
TI  - Th1 and Th17 cytokines drive inflammation in Takayasu arteritis.
AB  - OBJECTIVE: Takayasu arteritis (TAK) is a large-vessel vasculitis that induces
      damage to the aorta and its branches. Glucocorticoids remain the gold standard of
      therapy for TAK. The nature of the T cells driving vascular inflammation and the
      effects of glucocorticoids on the systemic components of TAK are not understood.
      The aim of this study was to analyze T cell homeostasis and cytokine production
      in peripheral blood and inflammatory lesions of the aorta in patients with TAK.
      METHODS: T cell homeostasis and cytokine production in peripheral blood and
      inflammatory lesions of the aorta were analyzed using Luminex analysis, flow
      cytometry, and immunohistochemical analysis. The study included 41 patients
      fulfilling the American College of Rheumatology 1990 criteria for the
      classification of TAK (17 patients with active TAK and 24 patients with disease
      in remission), 30 patients with giant cell arteritis and 39 patients with
      Behcet's disease (disease controls), and 20 age- and sex-matched healthy control
      subjects. RESULTS: We observed a marked increase in the expression of Th1 and
      Th17 cells, which correlated with TAK disease activity. The addition of serum
      from patients with active TAK to sorted CD4+ T cells from healthy donors in
      culture medium induced significant production of interferon-gamma (IFNgamma) and
      interleukin-17A (IL-17A). We demonstrated the presence of IFNgamma-, IL-6-, and
      IL-17A-producing T cells in vascular inflammatory infiltrates in patients with
      TAK. Corticosteroid therapy was associated with decreased levels of circulating
      Th1 cytokines in corticosteroid-treated patients with TAK compared with steroid
      free patients with TAK (for IL-2, mean +/- SD 5,079 +/- 5,300 versus 7,359 +/-
      3,197 pg/ml; for IFNgamma, 2,592 +/- 3,072 versus 8,393 +/- 3,392 pg/ml; for
      tumor necrosis factor alpha, 847 +/- 724 versus 1,491 +/- 392 pg/ml). However,
      glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL
      1 receptor, IL-17, and IL-23). CONCLUSION: The Th17 and Th1 pathways contribute
      to the systemic and vascular manifestations of TAK. Glucocorticoid treatment
      suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.

PMID- 25604825
TI  - Different roles of electromagnetic field experts when giving policy advice: an
      expert consultation.
AB  - BACKGROUND: The overall evidence for adverse health effects of electromagnetic
      fields (EMF) at levels of exposure normally experienced by the public is
      generally considered weak. However, whether long-term health effects arise
      remains uncertain and scientific policy advice is therefore given against a
      background of uncertainty. Several theories exist about different roles that
      experts may take when they provide advice on complex issues such as EMF. To
      provide empirical evidence for these theories, we conducted an expert
      consultation with as main research question: What are the different roles of EMF
      experts when they provide policy advice? METHODS: Q methodology was used to
      empirically test theoretical notions on the existence and determinants of
      different expert roles and to analyze which roles actually play out in the domain
      of EMF. Experts were selected based on a structured nominee process. In total 32
      international EMF experts participated. Responses were analyzed using Principal
      Component Analysis and for the open questions we used Atlas.ti. RESULTS: Four
      expert roles were found. Most striking differences between the four roles are
      whether experts consider current EMF policies adequate or not, whether additional
      -precautionary- measures are needed, and how experts view their position vis-a
      vis policymakers and/or other stakeholders. CONCLUSION: This empirical study
      provides support for the so far mainly theoretical debate about the existence of
      different roles of experts when they give policy advice. The experts' assessment
      of the degree of uncertainty of the issue turned out to be highly associated with
      their role. We argue that part of the controversy that exists in the debate
      regarding scientific policy advice on EMF is about different values and roles.

PMID- 25604826
TI  - Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog
      pathway to impede sustained temozolomide response in GBM.
AB  - Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained
      response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy
      response in GBM is predetermined in its neoplastic clones via a specific set of
      mutations that alter relevant pathways. We describe exome-wide enrichment of
      variant allele frequencies (VAFs) in neurospheres displaying contrasting
      phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of
      VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ
      effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ
      effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell
      cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells
      whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh)
      pathways in reversible TMZ-effect cells. Next, we validated the likely
      involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as
      well as on GBM patients, by extracting RNA-sequencing-based gene expression data
      from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ
      non-responder neurosphere in vitro by treating them with the FDA-approved
      pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate
      that the Hh-pathway impedes sustained TMZ-response in GBM and could be a
      potential therapeutic target to enhance TMZ-response in this malignancy. 

PMID- 25604828
TI  - Preparation of 4-butylaniline-bonded silica gel for the solid-phase extraction of
      flavone glycosides.
AB  - To extract flavone glycosides efficiently, a new extraction material based on 4
      butylaniline-bonded silica gel was prepared using a two-step grafting method
      including a ring-opening reaction and synchronous hydrolysis. Preparation of the
      silica-based material was easily achieved under mild conditions, and the material
      was characterized by Fourier transform infrared spectroscopy, elemental analysis,
      and scanning electron microscopy. The material was used in solid-phase
      extraction, and the extraction can be performed in neutral conditions without
      regard to ionic strength. Selectivity tests of 14 compounds on the extraction
      cartridge showed that the material has a high affinity to flavone glycosides in
      contrast to octadecyl silica, and the extraction yields for four flavone
      glycosides were found to be >93%. Selectivity tests further reveal that the
      adsorption on its surface is likely attributed to multiple interactions,
      including hydrophobic interactions, pi-pi interactions, and hydrogen bonding. To
      explore the applicability of 4-butylaniline-bonded silica gel, naringin and
      hesperidin from Simotang oral liquid were extracted, and the extraction yields
      were >90%, which is distinguished from <28% on octadecyl silica cartridge. 

PMID- 25604829
TI  - Inflammation and epilepsy in the developing brain: clinical and experimental
      evidence.
AB  - There is an increasing evidence to support a role of inflammatory processes in
      epilepsy. However, most clinical and experimental studies have been conducted in
      adult patients or using adult rodents. The pediatric epilepsies constitute a
      varied group of diseases that are most frequently age specific. In this review,
      we will focus on the possible role of inflammation in pediatric epilepsy
      syndromes. We will first describe the clinical data available and provide an
      overview of our current understanding of the role of inflammation in these
      clinical situations. We will then review experimental data regarding the role of
      inflammation in epilepsy in the developing brain. To summarize, inflammation
      contributes to seizure precipitation, and reciprocally, prolonged seizures induce
      inflammation. There is also a relationship between inflammation and cell injury
      following status epilepticus, which differs according to the developmental stage.
      Finally, inflammation seems to contribute to epileptogenesis even in the
      developing brain. Based on the available data, we highlight the need for further
      studies dissecting the exact role of inflammation in epilepsy during development.

PMID- 25604827
TI  - Socio-economic resources, young child feeding practices, consumption of highly
      processed snacks and sugar-sweetened beverages: a population-based survey in
      rural northwestern Nicaragua.
AB  - BACKGROUND: Socio-economic resources may be associated with infant feeding in
      complex patterns in societies undergoing a nutrition transition. This study
      evaluates associations of housing quality, food security and maternal education
      to the World Health Organization (WHO) feeding recommendations and to consumption
      of highly processed snacks (HP snacks) and sugar-sweetened beverages (SSBs) in
      rural Nicaragua. METHODS: Data were collected from May to November 2009, with
      mothers of 0- to 35-month-olds being asked about young child feeding using a food
      frequency questionnaire. A validated questionnaire was used to assess household
      food insecurity and data were collected on maternal education and housing
      quality. Pearson's chi-squared test was used to compare proportions and determine
      associations between the resources and young child feeding. The three socio
      economic resources and other confounders were introduced to multivariate logistic
      regression analyses to assess the independent contribution of the resources to
      the feeding practices and consumption of HP snacks and SSBs. RESULTS: Mothers
      with the lowest education level were more likely to be exclusively breastfeeding
      (EBF) their infants (OR not EBF: 0.19; 95% CI: 0.07, 0.51), whilst mothers of 6-
      to 35-month-olds in the lowest education category had more inadequate dietary
      diversity (DD) (OR for not meet DD: 2.04; 95% CI: 1.36, 3.08), were less likely
      to consume HP snacks (OR for HP snacks: 0.47; 95% CI: 0.32, 0.68) and SSBs (OR
      for SSBs: 0.68; 95% CI: 0.46, 0.98), compared to mothers with the highest level
      of education. Similarly, children residing in households with the highest food
      insecurity were also more prone to have inadequate dietary diversity (OR for not
      meet DD: 1.47; 95% CI: 1.05, 2.05). The odds for double burden of suboptimal
      feeding (concurrent inadequate diet and consumption of HP snacks/SSBs) were
      significantly lower in children of least educated mothers (OR: 0.64; 95% CI:
      0.44, 0.92). CONCLUSIONS: Higher level of education was associated with both more
      and less adherence to the WHO recommended feeding practices as well as with more
      consumption of HP snacks and SSBs. Regardless of educational strata, the children
      in the community were exposed to suboptimal feeding practices conducive to both
      under- as well as overnutrition.

PMID- 25604830
TI  - A general framework for a reliable multivariate analysis and pattern recognition
      in high-dimensional epidemiological data, based on cluster robustness: a tutorial
      to enrich the epidemiologists' toolkit.
AB  - BACKGROUND: In an epidemiologist's toolbox, three main types of statistical tools
      can be found: means and proportions comparisons, linear or logistic regression
      models and Cox-type regression models. All these techniques have their own
      multivariate formulations, so that biases can be accounted for. Nonetheless,
      there is an entire set of natively massive multivariate techniques, which are
      based on weaker assumptions than classical statistical techniques are, and which
      seem to be underestimated or remain unknown to most epidemiologists. These
      techniques are used for pattern recognition or clustering - that is, for
      retrieving homogeneous groups in data without any a priori about these groups.
      They are widely used in connex domains such as genetics or biomolecular studies.
      METHODS: Most clustering techniques require tuning specific parameters so that
      groups can be identified in data. A critical parameter to set is the number of
      groups the technique needs to discover. Different approaches to find the optimal
      number of groups are available, such as the silhouette approach and the
      robustness approach. This article presents the key aspects of clustering
      techniques (how proximity between observations is defined and how to find the
      number of groups), two archetypal techniques (namely the k-means and PAM
      algorithms) and how they relate to more classical statistical approaches.
      RESULTS: Through a theoretical, simple example and a real data application, we
      provide a complete framework within which classical epidemiological concerns can
      be reconsidered. We show how to (i) identify whether distinct groups exist in
      data, (ii) identify the optimal number of groups in data, (iii) label each
      observation according to its own group and (iv) analyze the groups identified
      according to separate and explicative data. In addition, how to achieve
      consistent results while removing sensitivity to initial conditions is explained.
      CONCLUSIONS: Clustering techniques, in conjunction with methods for parameter
      tuning, provide the epidemiologist with substantial additional tools. They differ
      from the usual approaches based on hypothesis-testing because no assumptions are
      made on the data and these clustering techniques are natively multivariate.

PMID- 25604831
TI  - [How do we catch flu? Beliefs in France in 2010].
AB  - AIMS: Our goals were to describe beliefs held by French people concerning the
      contagiosity of influenza and analyze the relationship of these beliefs with
      vaccination against seasonal flu. METHODS: A subsample (4749 people aged 15-79)
      of the Health Barometer 2010 responded to questions dealing with influenza.
      Responses were analyzed using clustering analysis and logistic regression.
      RESULTS: Overall, observed beliefs were quite good, but also socially
      differentiated. 'False' beliefs were more frequent among people with a lower
      socioeconomic status. Those who overestimated the contagiosity of influenza were
      less likely to have been vaccinated against seasonal influenza in 2008.
      CONCLUSIONS: The beliefs analyzed here were associated with vaccination
      behaviors. 'False' beliefs may be difficult to change as they are nevertheless
      coherent. These beliefs also exhibit social inequalities that should be taken
      into account when determining preventive measures.

PMID- 25604832
TI  - Assessment of the quality of Internet information on sleeve gastrectomy.
AB  - BACKGROUND: The Internet is an important source of information for morbidly obese
      patients who are potential candidates for bariatric procedures. Over the past few
      years, there is growing demand for sleeve gastrectomy because of perceived
      technical ease balanced with excellent outcomes. The aim of this study was to
      assess the quality and content of available internet information pertaining to
      sleeve gastrectomy. Our hypothesis is that this information is inconsistent and
      inaccurate. METHODS: A total of 50 websites were analyzed in September 2013. We
      used the search term "sleeve gastrectomy" to identify sites on the most common
      internet search engines: Google, Yahoo, Bing, and Ask. Based on popularity of
      use, 20 websites were obtained through the Google engine and 10 sites by each of
      the others. Websites were classified as academic, physician, health professional,
      commercial, social media, and unspecified. Quality of information was evaluated
      using the DISCERN score, the Journal of the American Medical Association (JAMA)
      benchmark criteria, and the Health on the Net code (HONcode) seal accreditation.
      The DISCERN score varies from 0-80 points and is based on 16 questions that
      evaluate publication quality and reliability. The JAMA benchmark criteria range
      from 0-4 points assessing website authorship, attribution, disclosure, and
      currency. HONcode certification was assessed as present or absent website
      accreditation. Duplicate and inaccessible websites were excluded from the
      analysis. RESULTS: We identified 43 websites from the United States, 6 from
      Mexico, and 1 from Australia. The average DISCERN and JAMA benchmark scores for
      all websites were 46.3+/-14.5 and 1.6+/-1.1, respectively, with a median DISCERN
      of 48.5 (range, 16-76) and JAMA score of 2.0 (range, 0-4). Website classification
      distribution was 21 physician, 11 academic, 7 commercial, 5 social media, 4
      unspecified, and 2 health professional. The average DISCERN and JAMA benchmark
      scores were 55.4+/-13.4 and 2.4+/-1.0 in the academic group, 49.5+/-10.0 and
      1.9+/-.9 in the physician group, 46.9+/-14.2 and .2+/-.4 in social media sites,
      44.0+/-2.8 and 1.0+/-.0 in health professional pages, 41.3+/-14.2 and 1.0+/-1.0
      in commercial sites, and 39.8+/-19.5 and 1.0+/-1.1 in the unspecified group. The
      HONcode seal was present in 2 (4%) of the websites analyzed. CONCLUSION: The
      results of this study suggest poor quality and content of information on the
      internet viewed by potential bariatric candidates. Only 4% of the websites
      demonstrated HONcode seal accreditation. The global mean DISCERN and JAMA
      benchmark scores reported in this study were significantly lower than one would
      expect. Academic and physician websites offer the best information content
      whereas the worst was observed in the commercial and unspecified groups.

PMID- 25604833
TI  - Review of family-based approaches to improve postoperative outcomes among
      bariatric surgery patients.
AB  - BACKGROUND: Bariatric surgery must be partnered with postoperative lifestyle
      modifications for enduring weight loss and related health effects to be fully
      appreciated. Little is known about how these lifestyle modifications may be
      affected by the involvement of other family members living in the household;
      therefore, this review describes current family-based approaches to improving
      postoperative outcomes in bariatric surgery patients and their families. METHODS:
      A MEDLINE search of publications from 1999 to 2014 was conducted in January 2014.
      Retrieved titles and abstracts were assessed by 2 authors to determine relevance
      to the topic surrounding family-based approaches to improve postbariatric surgery
      outcomes. All study designs except case studies were considered if they included
      some aspect of family as a predictor in relation to improved health outcomes
      after surgery. RESULTS: Initial searches yielded 650 publications (bariatric
      surgery+family, n = 193; bariatric surgery+child, n = 338; bariatric
      surgery+spouse, n = 4; bariatric surgery+social support, n = 115). Two studies
      met criteria for a family-based approach to improving metabolic outcomes in
      bariatric patients. Seven studies discussed the impact of bariatric surgery on
      families. All other studies were excluded for not discussing family-based
      approaches. CONCLUSION: Despite limited documentation of family-based approaches
      on improving health outcomes in patients who underwent bariatric surgery,
      evidence suggests that such an approach may be advantageous if planned a priori
      to occur before, during, and after bariatric surgery. Future studies could test
      the combination of bariatric surgery and a family-based approach for improved
      metabolic outcomes in both the patient and involved family member(s).

PMID- 25604834
TI  - Causes and risk factors for mortality within 1 year after obesity surgery in a
      population-based cohort study.
AB  - BACKGROUND: The use of obesity surgery has increased during the past decade.
      There is a need for population-based assessments of causes and risk factors for
      postoperative mortality. The objective of this study was to assess causes and
      risk factors for 1-year mortality after obesity surgery. METHODS: This nationwide
      retrospective population-based cohort study included essentially all obesity
      surgery patients in Sweden from 1980-2010. Data were collected from Swedish
      national registries and medical records. Patient characteristics, co-morbidities,
      and surgical procedures were assessed in relation to 1-year mortality through
      multivariable Cox proportional hazards regression, providing hazard ratios (HR),
      and 95% confidence intervals (CI) adjusted for age, sex, surgical procedure,
      surgical access, and co-morbidity. RESULTS: Among 22,487 obesity surgery patients
      the 1-year cumulative mortality was .38% (n = 85). Follow-up of cohort was
      complete. Median time of postoperative death was 45 days. Main causes of death
      included cardiopulmonary complications (myocardial infarction [n = 14; 16%],
      pulmonary embolism [n = 12; 14%], sudden cardiac arrest [n = 11; 13%]), and
      anastomotic leak (n = 12; 14%). Male sex (HR = 2.31; 95% CI 1.48-3.60), diabetes
      (HR = 2.47; 95% CI 1.44-4.23), and congestive heart failure (HR = 4.82; 95% CI
      2.25-10.35) were independently associated with increased 1-year mortality, while
      age, hypertension, cerebrovascular disease, coronary heart disease, chronic
      obstructive pulmonary disease, asthma, and surgical procedure were not. Open
      surgery entailed an increased mortality compared to laparoscopic surgery from
      2000-2010 (HR = 2.72; 95% CI 1.53-4.83), but not from 1990-1999 (HR = .39; 95% CI
      .11-1.32). CONCLUSION: Although the absolute risk of mortality is low, the
      increased relative risk of mortality associated with male sex, diabetes,
      congestive heart failure, and open surgical access could influence clinical
      decision making.

PMID- 25604836
TI  - [Diabetic neuropathy: do not only consider distal symmetrical neuropathy].
AB  - BACKGROUND: Diabetic neuropathy is a common complication of diabetes mellitus.
      The length-dependent symmetrical sensorimotor type of neuropathy is the most
      prevalent form of diabetic neuropathy but other forms of diabetic neuropathy also
      need to be kept in mind. Their differential diagnosis is often more challenging
      but implicates specific forms of treatment other than improvement of metabolic
      control. AIM OF THE STUDY: This article gives an overview of the less frequent
      forms of diabetic neuropathy and discusses their impact, diagnostic and
      therapeutic implications. RESULTS: Autonomic diabetic neuropathy, diabetic small
      fiber neuropathy and less frequent forms of diabetic neuropathy, such as diabetic
      radiculoplexopathy, diabetic neuropathy of cranial nerves, therapy-induced
      neuropathy and alternative causes of peripheral neuropathy in patients with
      diabetes are described. DISCUSSION: Diagnosis of less frequent subtypes of
      diabetic neuropathy and differentiation towards alternative causes of peripheral
      neuropathy are often difficult in daily medical routine. Diagnostic clues are
      helpful in identifying rarer forms of diabetic neuropathy, thus enabling more
      specific treatment.

PMID- 25604835
TI  - Integrin binding by Borrelia burgdorferi P66 facilitates dissemination but is not
      required for infectivity.
AB  - P66, a Borrelia burgdorferi surface protein with porin and integrin-binding
      activities, is essential for murine infection. The role of P66 integrin-binding
      activity in B. burgdorferi infection was investigated and found to affect
      transendothelial migration. The role of integrin binding, specifically, was
      tested by mutation of two amino acids (D205A,D207A) or deletion of seven amino
      acids (Del202-208). Neither change affected surface localization or channel
      forming activity of P66, but both significantly reduced binding to alphav beta3 .
      Integrin-binding deficient B. burgdorferi strains caused disseminated infection
      in mice at 4 weeks post-subcutaneous inoculation, but bacterial burdens were
      significantly reduced in some tissues. Following intravenous inoculation, the
      Del202-208 bacteria were below the limit of detection in all tissues assessed at
      2 weeks post-inoculation, but bacterial burdens recovered to wild-type levels at
      4 weeks post-inoculation. The delay in tissue colonization correlated with
      reduced migration of the Del202-208 strains across microvascular endothelial
      cells, similar to Deltap66 bacteria. These results indicate that integrin binding
      by P66 is important to efficient dissemination of B. burgdorferi, which is
      critical to its ability to cause disease manifestations in incidental hosts and
      to its maintenance in the enzootic cycle. 

PMID- 25604837
TI  - [University professors in the Soviet Occupation Zone and the German Democratic
      Republic up to 1961: Academic alternation of generations at university
      psychiatric hospitals].
AB  - After WWII a politically guided staffing policy foresaw an exchange program for
      professors from the Soviet Occupation Zone and the German Democratic Republic
      (GDR). In the field of medicine this initiative was not successful. With respect
      to university psychiatric/neurological hospitals this experiment failed as a
      result of a shortage of personnel due to the consequences of war, denazification
      and people migrating into western occupation zones. Criteria for politically
      selecting promising young talent which had been propagated by the Socialist Unity
      Party of Germany (Sozialistische Einheitspartei Deutschlands, SED) were thus not
      relevant in academic medicine until 1961; however, the communist rulers had great
      interest in bringing professional and academic resources up to date. Politically
      implicated representatives in the field were also included in this process. At
      the forefront was the interest in functioning medical care and education in order
      to be able to train much needed health professionals. At the end of the 1950s a
      new generation of professors was established at the university hospitals. This
      generation rotation demonstrated the politically intended replacement of the
      "old" professor generation and the transition to a new GDR generation that had
      been trained after 1945. This second generation of professors inherited vacant
      professorships and defined and shaped research and academia until the end of the
      GDR much more than the previous generation had and also more than the one that
      followed. The generation of professors continued to feel a strong affiliation
      with their academic teachers and consequently continued their tradition in the
      sense of a school, for the most part independent of political circumstances.

PMID- 25604839
TI  - [Hospital readmission induced by adverse drug reaction: a pilot study in a post
      emergency unit of a French university hospital].
AB  - PURPOSE: Adverse Drug Reactions (ADRs) leading to hospital admission was
      estimated to 3.6 to 21.7%. Despite its importance in terms of patients care,
      readmission to hospital due to ADRs remains poorly documented. The aim of our
      study was to investigate the rate and main characteristics of readmission for
      ADRs. METHODS: We undertook a retrospective study during two years (2011-2012) in
      the post-emergency unit of Toulouse university hospital (south western, France).
      We selected all unplanned hospitalization for acute disease and included all
      cases of patients admitted twice fold or more for ADRs. Characteristics of drug
      induced ADRs were assessed according to appropriate use or not. RESULTS: Out of
      the 197 readmitted patients, 71 was related to ADRs (3.6%) corresponding to
      17.80/00 patients-year. Mean age was 82.3 years and 67% were women. The most
      frequent ADRs found were vascular (n=41, 18.4%), gastro-intestinal (n=28, 12.6%),
      cardiac (n=28, 12.6%), neurologic (n=26, 11.7%), metabolic (n=26, 10.3%) and
      psychiatric (n=24, 9.9%). The drugs mainly involved were psychoactive,
      cardiovascular, digestive or antithrombotic agents. The context of occurrence of
      ADRs was related to inappropriate drug prescription in 56% of cases. A total of
      24 patients were admitted twice for the same ADR and 2 others three times. For 22
      patients (30.9%), the same drugs were involved. CONCLUSION: Our data show
      hospital readmission was due to ADRs in 3.6% of cases. In 1.1% of cases, the same
      couple "drug-ADR" was involved. Furthermore, in 56% of cases, repeated admissions
      are related to an inappropriate drug prescription.

PMID- 25604840
TI  - [Obstetricians have friends in all the departments of the hospital].

PMID- 25604838
TI  - [Tryptophan immunoadsorption for multiple sclerosis and neuromyelitis optica:
      therapy option for acute relapses during pregnancy and breastfeeding].
AB  - BACKGROUND: Approximately 25 % of women with multiple sclerosis (MS) suffer
      clinically relevant relapses during pregnancy. Almost all disease-modifying drugs
      are contraindicated in pregnancy. High-dose glucocorticoids have some serious
      risks, especially within the first trimester. Tryptophan immunoadsorption (IA)
      provides a safe option to treat MS relapses during pregnancy. OBJECTIVES: In this
      case series we describe for the first time the use of tryptophan IA for MS and
      neuromyelitis optica (NMO) relapses during pregnancy and breastfeeding. PATIENTS
      AND METHODS: In this study a total of 9 patients were retrospectively analyzed of
      which 7 patients received IA treatment during pregnancy, 2 during breastfeeding
      and 4-6 tryptophan IA treatments were performed per patient with the single use
      tryptophan adsorber. Primary outcome was symptom improvement of the relapse.
      RESULTS: In this study four patients with MS and one with NMO relapse during
      pregnancy were treated with IA without preceding glucocorticoid pulse therapy.
      The MS patients showed improvement in the expanded disability status scale (EDSS)
      by at least one point, the NMO patient showed significant improvement in visual
      acuity and two pregnant patients with steroid-refractory relapses showed
      clinically relevant improvement after IA. Of the patients two suffered from
      steroid-refractory relapses during breastfeeding and relapse symptoms improved in
      both cases after treatment with IA. All treatments were well tolerated and no
      serious adverse events occurred. CONCLUSION: Tryptophan IA was found to be safe,
      well-tolerated and effective in the treatment of MS and NMO relapses during
      pregnancy and breastfeeding, sometimes without preceding glucocorticoid pulse
      therapy. A binding recommendation is limited without prospective clinical
      studies.

PMID- 25604841
TI  - Impact of the atomic layer deposition precursors diffusion on solid-state carbon
      nanotube based supercapacitors performances.
AB  - A study on the impact of atomic layer deposition (ALD) precursors diffusion on
      the performance of solid-state miniaturized nanostructure capacitor array is
      presented. Three-dimensional nanostructured capacitor array based on double
      conformal coating of multiwalled carbon nanotubes (MWCNTs) bundles is realized
      using ALD to deposit Al2O3 as dielectric layer and TiN as high aspect-ratio
      conformal counter-electrode on 2 MUm long MWCNT bundles. The devices have a small
      footprint (from 100 MUm(2) to 2500 MUm(2)) and are realized using an IC wafer
      scale manufacturing process with high reproducibility (<=0.3E-12F deviation). To
      evaluate the enhancement of the electrode surface, the measured capacitance
      values are compared to a lumped circuital model. The observed discrepancies are
      explained with a partial coating of the CNT, that determine a limited use of the
      available electrode surface area. To analyze the CNT coating effectiveness, the
      ALD precursors diffusions inside the CNT bundle is studied using a Knudsen
      diffusion mechanism. 

PMID- 25604842
TI  - Autoradiography techniques and quantification of drug distribution.
AB  - The use of radiolabeled drug compounds offers the most efficient way to quantify
      the amount of drug and/or drug-derived metabolites in biological samples.
      Autoradiography is a technique using X- ray film, phosphor imaging plates, beta
      imaging systems, or photo-nuclear emulsion to visualize molecules or fragments of
      molecules that have been radioactively labeled, and it has been used to quantify
      and localize drugs in tissues and cells for decades. Quantitative whole-body
      autoradiography or autoradioluminography (QWBA) using phosphor imaging technology
      has revolutionized the conduct of drug distribution studies by providing high
      resolution images of the spatial distribution and matching tissue concentrations
      of drug-related radioactivity throughout the body of laboratory animals. This
      provides tissue-specific pharmacokinetic (PK) compartmental analysis which has
      been useful in toxicology, pharmacology, and drug disposition/patterns, and to
      predict human exposure to drugs and metabolites, and also radioactivity, when a
      human radiolabeled drug study is necessary. Microautoradiography (MARG) is
      another autoradiographic technique that qualitatively resolves the localization
      of radiolabeled compounds to the cellular level in a histological preparation.
      There are several examples in the literature of investigators attempting to
      obtain drug concentration data from MARG samples; however, there are technical
      issues which make that problematic. These issues will be discussed. This review
      will present a synopsis of both techniques and examples of how they have been
      used for drug research in recent years. 

PMID- 25604843
TI  - Diffusion tensor MR imaging of white matter integrity in HIV-positive patients
      with planning deficit.
AB  - INTRODUCTION: The aim of this study was to evaluate whether normal controls and
      human immunodeficiency virus (HIV) patients with and without planning deficits
      differ on white matter integrity. METHODS: A total of 34 HIV-positive patients
      with planning deficits were compared with 13 HIV-positive patients without
      planning deficits and 19 gender-, age-, and education-matched control subjects.
      Diffusion tensor imaging (DTI) was performed along 30 noncolinear directions in a
      1.5-T scanner. For tract-based spatial statistics analysis, a white matter
      skeleton was created, and a permutation-based inference with 5000 permutations
      with a threshold of p < 0.05 was used to identify abnormalities in fractional
      anisotropy (FA). The median, radial, and axial diffusivities were also projected
      onto the mean FA skeleton. RESULTS: Compared with controls, HIV-positive patients
      with planning deficits had decreased FA in bilateral anterior thalamic
      radiations, bilateral inferior fronto-occiptal fasciculi, genu and splenium of
      the corpus callosum, bilateral superior longitudinal fascicule, and bilateral
      uncinate fasciculi. Compared to HIV-positive patients without planning deficits,
      patients with planning deficits had decreased FA in bilateral anterior thalamic
      radiations, bilateral inferior fronto-occiptal fasciculi, genu of the corpus
      callosum, bilateral superior longitudinal fascicule, and right uncinate
      fascicule. CONCLUSION: DTI can detect extensive white matter abnormalities in the
      normal-appearing white matter of HIV-positive patients with planning deficits
      compared with controls and HIV-positive patients without planning deficits.

PMID- 25604844
TI  - Proteomic analysis of tilapia Oreochromis niloticus Streptococcus agalactiae
      strains with different genotypes and serotypes.
AB  - Nine tilapia Oreochromis niloticus group B streptococcus (GBS) strains differing
      in serotype and genotype were selected and paired. Two-dimensional difference gel
      electrophoresis (2D DIGE) and matrix-assisted laser-desorption ionization time-of
      flight-mass spectrometry (MALDI-TOF-MS) were used to analyse the protein profiles
      of the strain pairs. Forty-three proteins corresponding to 66 spots were
      identified, of which 35 proteins were found in the seven selected strain pairs
      that represented pairs differing in genotype and serotype. Among the 35 proteins,
      numbers of differentially expressed proteins in strains of different serotypes
      were greater than found in strains of different genotypes, suggesting that
      serotype plays a more essential role than genotype in the differential protein
      expression among GBS strains. No distinct pattern was found with respect to
      genotype and the protein expression profile of GBS strains. Several proteins were
      identified as surface-associated cytoplasmic proteins that possessed the typical
      immunity-eliciting characteristics of surface proteins. The identified proteins
      were found to be involved in 16 biological processes and seven Kyoto
      encyclopaedia of genes and genomes (KEGG) pathways. The data, for the first time,
      identified differentially expressed proteins in O. niloticus GBS strains of
      different serotypes, which play a major role in immunogenicity of O. niloticus
      GBS than does genotype, offering further information for design of a vaccine
      against O. niloticus GBS.

PMID- 25604845
TI  - Rural-to-Urban Migration and Changes in Health Among Young Adults in Thailand.
AB  - We investigate the impacts of rural-to-urban migration on the health of young
      adult migrants. A key methodological challenge involves the potentially
      confounding effects of selection on the relationship between migration and
      health. Our study addresses this challenge in two ways. To control for potential
      effects of prior health status on post-migration health outcomes, we employ a
      longitudinal approach. To control for static unobserved characteristics that can
      affect migration propensity as well as health outcomes, we use fixed-effects
      analyses. Data were collected in 2005 and 2007 for a cohort of young adults in
      rural Kanchanaburi province, western Thailand. The migrant sample includes
      individuals who subsequently moved to urban destinations where they were
      reinterviewed in 2007. Return migrants were interviewed in rural Kanchanaburi in
      both years but moved to an urban area and returned in the meantime. A rural
      comparison group comprises respondents who remained in the origin villages. An
      urban comparison sample includes longer-term residents of the urban destination
      communities. Physical and mental health measures are based on the SF-36 health
      survey. Findings support the "healthy migrant hypothesis." Migrants are
      physically healthier than their nonmigrant counterparts both before and after
      moving to the city. We did not find an effect of migration on physical health.
      Rural-to-urban migrants who stayed at destination experienced a significant
      improvement in mental health status. Fixed-effects analyses indicate that rural
      to-urban migration positively affects mental health. Return migrants do not fare
      as well as migrants who stayed at destination on both physical and mental health
      status--evidence of selective return migration.

PMID- 25604846
TI  - Potential (Mis)match? Marriage Markets Amidst Sociodemographic Change in India,
      2005-2050.
AB  - We explore the impact of sociodemographic change on marriage patterns in India by
      examining the hypothetical consequences of applying three sets of marriage
      pairing propensities-contemporary patterns by age, contemporary patterns by age
      and education, and changing propensities that allow for greater educational
      homogamy and reduced educational asymmetries--to future population projections.
      Future population prospects for India indicate three trends that will impact
      marriage patterns: (1) female deficit in sex ratios at birth; (2) declining birth
      cohort size; (3) female educational expansion. Existing literature posits
      declining marriage rates for men arising from skewed sex ratios at birth (SRBs)
      in India's population. In addition to skewed SRBs, India's population will
      experience female educational expansion in the coming decades. Female educational
      expansion and its impact on marriage patterns must be jointly considered with
      demographic changes, given educational differences and asymmetries in union
      formation that exist in India, as across much of the world. We systematize
      contemporary pairing propensities using data from the 2005-2006 Indian National
      Family Health Survey and the 2004 Socio-Economic Survey and apply these and the
      third set of changing propensities to multistate population projections by
      educational attainment using an iterative longitudinal projection procedure. If
      today's age patterns of marriage are viewed against age/sex population
      composition until 2050, men experience declining marriage prevalence. However,
      when education is included, women--particularly those with higher education-
      experience a more salient rise in nonmarriage. Significant changes in pairing
      patterns toward greater levels of educational homogamy and gender symmetry can
      counteract a marked rise in nonmarriage.

PMID- 25604847
TI  - Geographic migration of black and white families over four generations.
AB  - This article analyzes patterns of geographic migration of black and white
      American families over four consecutive generations. The analysis is based on a
      unique set of questions in the Panel Study of Income Dynamics (PSID) asking
      respondents about the counties and states in which their parents and grandparents
      were raised. Using this information along with the extensive geographic
      information available in the PSID survey, the article tracks the geographic
      locations of four generations of family members and considers the ways in which
      families and places are linked together over the course of a family's history.
      The patterns documented in the article are consistent with much of the
      demographic literature on the Great Migration of black Americans out of the
      South, but they reveal new insights into patterns of black migration after the
      Great Migration. In the most recent generation, black Americans have remained in
      place to a degree that is unique relative to the previous generation and relative
      to whites of the same generation. This new geographic immobility is the most
      pronounced change in black Americans' migration patterns after the Great
      Migration, and it is a pattern that has implications for the demography of black
      migration as well as the literature on racial inequality. 

PMID- 25604848
TI  - Characteristics of nighttime reflux assessed using multichannel intraluminal
      impedance pH monitoring and a portable electroencephalograph.
AB  - Gastroesophageal reflux disease (GERD) is strongly associated with sleep
      disturbances. Although the mechanisms of this association have not been fully
      elucidated, nighttime reflux plays a central role. However, the detailed
      characteristics of nighttime reflux occurring during sleep are unknown. The aim
      of the present study was to examine the characteristics and prevalence of
      nighttime reflux in the natural sleep environment of GERD patients. Seventeen
      patients experiencing daily moderate-to-severe heartburn and/or regurgitation
      were studied using multichannel intraluminal impedance pH monitoring and
      electroencephalography off-proton pump inhibitor treatment. Nighttime reflux was
      divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or
      alkaline) and extent (distal only or proximal migration) according to the
      standard criteria. Nighttime phases were divided as follows: recumbent-awake
      before falling asleep, nonrapid eye movement, rapid eye movement, awakening from
      sleep, and post-awakening in the morning. Among 184 nighttime refluxes, 43 (23%)
      occurred during recumbent-awake before falling asleep, 28 (15%) during nonrapid
      eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from
      sleep, and 13 (7%) during post-awakening in the morning. Liquid reflux was more
      common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid
      eye movement (100%) compared with awakening before falling asleep (68%). The
      prevalence of proximal migration was significantly lower in nonrapid eye movement
      and rapid eye movement than in the other phases. There were no differences in
      acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events
      with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of
      nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of
      425 awakening episodes during sleep. Different reflux patterns at each phase
      during nighttime might explain the pathogenesis of GERD and its related sleep
      disturbances. 

PMID- 25604849
TI  - Skin Rash as the Only Manifestation of Mild Decompression Sickness.

PMID- 25604850
TI  - Observation of aliphatic C-H...X hydrogen bonds in imidazolium ionic liquids.
AB  - Measurement of H/D isotope effects on the (19)F resonances of sequentially
      deuterated 1-n-butyl-3-methylimidazolium hexafluorophosphate and
      tetrafluoroborate isotopologues reveals the formation of aliphatic C-H...X
      hydrogen bonds between the fluorinated anions and protons along the N-alkyl
      sidechains of the cations.

PMID- 25604851
TI  - Randomized multicenter phase III study of a modified docetaxel and cisplatin plus
      fluorouracil regimen compared with cisplatin and fluorouracil as first-line
      therapy for advanced or locally recurrent gastric cancer.
AB  - BACKGROUND: The V325 study showed that docetaxel, cisplatin, and fluorouracil
      (DCF) prolonged overall survival (OS) of patients with advanced gastric cancer,
      but with a high incidence of dose-limiting toxicities. We investigated the
      efficacy and safety of a modified DCF (mDCF) regimen for Chinese patients with
      advanced gastric cancer. METHODS: Untreated advanced gastric cancer patients
      randomly received docetaxel and cisplatin at 60 mg/m(2) (day 1) followed by
      fluorouracil at 600 mg/m(2)/day (days 1-5; mDCF regimen) or cisplatin at 75
      mg/m(2) (day 1) followed by fluorouracil at 600 mg/m(2)/day (days 1-5; CF) every
      3 weeks. The primary end point was progression-free survival (PFS). The secondary
      end points were OS, overall response rate (ORR), time-to-treatment failure (TTF),
      and safety. RESULTS: In total, 243 patients were randomized to treatment (mDCF
      regimen 121; CF 122). Compared with CF, the mDCF regimen significantly improved
      PFS and OS: the median PFS was 7.2 and 4.9 months, respectively [hazard ratio
      (HR) 0.58, log-rank P = 0.0008], and the median OS was 10.2 and 8.5 months,
      respectively (HR = 0.71, P = 0.0319). Additionally, the mDCF regimen improved the
      parameters used as secondary objectives: the ORR was 48.7% with the mDCF regimen
      versus 33.9% with CF (P = 0.0244); the median TTF was 3.4 months with the mDCF
      regimen and 2.4 months with CF (HR = 0.67, P = 0.0027). Grade 3 and grade 4
      treatment-related adverse events occurred in 77.3 % of patients who received the
      mDCF regimen versus 46.1% of patients who received CF (P < 0.001). CONCLUSIONS:
      The mDCF regimen, compared with CF, significantly prolonged PFS and OS and
      enhanced ORR of Chinese patients with advanced gastric cancer. The mDCF regimen
      achieved efficacy comparable to that of DCF but with fewer toxicities, which is
      appropriate for the Chinese population.

PMID- 25604852
TI  - Do knee osteoarthritis and fat-free mass interact in their impact on health
      related quality of life in men? Results from a population-based cohort.
AB  - OBJECTIVE: To investigate whether obesity and other risk factors interact with
      knee osteoarthritis (OA) in its adverse impact on health-related quality of life
      (HRQOL). METHODS: In 1,262 participants of the Netherlands Epidemiology of
      Obesity Study, a population-based cohort (age 45-65 years, 53% women, and median
      body mass index [BMI] 27 kg/m(2) ), knee OA was defined following modified
      American College of Rheumatology criteria. BMI and fat-free mass (as proxy for
      muscle mass) were assessed by bioelectrical impedance analysis, and comorbidities
      by self-report. HRQOL was assessed using the Short Form 36 physical component
      summary (PCS) score. Linear regression analyses were performed to examine
      associations between knee OA and PCS score, adjusting for age and sex and
      stratified for BMI, fat-free mass, and comorbidities. RESULTS: Knee OA
      (prevalence 16%) was associated with a 7.2-points lower PCS score (95% confidence
      interval -9.5, -4.8). PCS score was also negatively associated with obesity and
      comorbidities; however, no interaction with knee OA was seen. Low fat-free mass
      was associated with a lower PCS score and interacted with knee OA in men.
      Interaction between concurring OA and low fat-free mass attributed to 64% of the
      decrease in PCS score, as compared with men without OA and with high fat-free
      mass. CONCLUSION: Knee OA was associated with a lower HRQOL, as were its risk
      factors, obesity, comorbidities, and low fat-free mass. In men, fat-free mass
      interacted with knee OA, leading to an additional decrease of HRQOL in the case
      of concurrence. Especially in the former, improvement of fat-free mass may
      improve HRQOL in knee OA patients.

PMID- 25604853
TI  - RMND1 deficiency associated with neonatal lactic acidosis, infantile onset renal
      failure, deafness, and multiorgan involvement.
AB  - RMND1 is an integral inner membrane mitochondrial protein that assembles into a
      large 240 kDa complex to support translation of the 13 polypeptides encoded on
      mtDNA, all of which are essential subunits of the oxidative phosphorylation
      (OXPHOS) complexes. Variants in RMND1 produce global defects in mitochondrial
      translation and were first reported in patients with severe neurological
      phenotypes leading to mortality in the first months of life. Using whole-exome
      sequencing, we identified compound heterozygous RMND1 variants in a 4-year-old
      patient with congenital lactic acidosis, severe myopathy, hearing loss, renal
      failure, and dysautonomia. The levels of mitochondrial ribosome proteins were
      reduced in patient fibroblasts, causing a translation defect, which was rescued
      by expression of the wild-type cDNA. RMND1 was almost undetectable by immunoblot
      analysis in patient muscle and fibroblasts. BN-PAGE analysis showed a severe
      combined OXPHOS assembly defect that was more prominent in patient muscle than in
      fibroblasts. Immunofluorescence experiments showed that RMND1 localizes to
      discrete foci in the mitochondrial network, juxtaposed to RNA granules where the
      primary mitochondrial transcripts are processed. RMND1 foci were not detected in
      patient fibroblasts. We hypothesize that RMND1 acts to anchor or stabilize the
      mitochondrial ribosome near the sites where the mRNAs are matured, spatially
      coupling post-transcriptional handling mRNAs with their translation, and that
      loss of function variants in RMND1 are associated with a unique constellation of
      clinical phenotypes that vary with the severity of the mitochondrial translation
      defect. 

PMID- 25604854
TI  - Research participants in NGS studies want to know about incidental findings.
AB  - Following the implementation of high-throughput sequencing legal and ethical
      issues are discussed intensively. The management of incidental findings (IFs) in
      a research setting have been investigated but there is a lack of literature
      concerning research participant's perspective. The aim of this study was to
      investigate whether research participants want disclosure of IFs and what kind of
      IFs they want to know about. One hundred and twenty-seven research participants
      in a study of gastrointestinal polyps were informed about whole-exome sequencing
      and the risk of IFs. They were asked to decide whether they (A) wanted disclosure
      of IFs no matter whether the variants were associated with a non-treatable or non
      preventable condition, (B) wanted disclosure of variants associated with
      treatable or preventable conditions or (C) wanted no disclosure at all.
      Participants who wanted disclosure of all the IFs (A) accounted for the majority
      (n=78), 45 of the participants only wanted disclosure of variants, which could
      lead to surveillance or treatment (B) and 4 participants did not want IFs to be
      disclosed at all (C). The study showed that almost all research participants
      wanted disclosure of at least some types of IFs. 

PMID- 25604855
TI  - Rare variants in beta-Amyloid precursor protein (APP) and Parkinson's disease.
AB  - Many individuals with Parkinson's disease (PD) develop cognitive deficits, and a
      phenotypic and molecular overlap between neurodegenerative diseases exists. We
      investigated the contribution of rare variants in seven genes of known relevance
      to dementias (beta-amyloid precursor protein (APP), PSEN1/2, MAPT (microtubule
      associated protein tau), fused in sarcoma (FUS), granulin (GRN) and TAR DNA
      binding protein 43 (TDP-43)) to PD and PD plus dementia (PD+D) in a discovery
      sample of 376 individuals with PD and followed by the genotyping of 25 out of the
      27 identified variants with a minor allele frequency <5% in 975 individuals with
      PD, 93 cases with Lewy body disease on neuropathological examination, 613
      individuals with Alzheimer's disease (AD), 182 cases with frontotemporal dementia
      and 1014 general population controls. Variants identified in APP were
      functionally followed up by Abeta mass spectrometry in transiently transfected
      HEK293 cells. PD+D cases harbored more rare variants across all the seven genes
      than PD individuals without dementia, and rare variants in APP were more common
      in PD cases overall than in either the AD cases or controls. When additional
      controls from publically available databases were added, one rare variant in APP
      (c.1795G>A(p.(E599K))) was significantly associated with the PD phenotype but was
      not found in either the PD cases or controls of an independent replication
      sample. One of the identified rare variants (c.2125G>A (p.(G709S))) shifted the
      Abeta spectrum from Abeta40 to Abeta39 and Abeta37. Although the precise
      mechanism remains to be elucidated, our data suggest a possible role for APP in
      modifying the PD phenotype as well as a general contribution of genetic factors
      to the development of dementia in individuals with PD. 

PMID- 25604857
TI  - Clinical Utility Gene Card for: Fibrodysplasia ossificans progressiva.

PMID- 25604856
TI  - Extensive genome-wide autozygosity in the population isolates of Daghestan.
AB  - Isolated populations are valuable resources for mapping disease genes, as
      inbreeding increases genome-wide homozygosity and enhances the ability to map
      disease alleles on a genetically uniform background within a relatively
      homogenous environment. The populations of Daghestan are thought to have resided
      in the Caucasus Mountains for hundreds of generations and are characterized by a
      high prevalence of certain complex diseases. To explore the extent to which their
      unique population history led to increased levels of inbreeding, we genotyped
      >550 000 autosomal single-nucleotide polymorphisms (SNPs) in a set of 14
      population isolates speaking Nakh-Daghestanian (ND) languages. The ND-speaking
      populations showed greatly elevated coefficients of inbreeding, very high numbers
      and long lengths of Runs of Homozygosity, and elevated linkage disequilibrium
      compared with surrounding groups from the Caucasus, the Near East, Europe,
      Central and South Asia. These results are consistent with the hypothesis that
      most ND-speaking groups descend from a common ancestral population that
      fragmented into a series of genetic isolates in the Daghestanian highlands. They
      have subsequently maintained a long-term small effective population size as a
      result of constant inbreeding and very low levels of gene flow. Given these
      findings, Daghestanian population isolates are likely to be useful for mapping
      genes associated with complex diseases. 

PMID- 25604859
TI  - Clinical utility gene card for: Arterial tortuosity syndrome.

PMID- 25604858
TI  - New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3).
AB  - X-linked recessive dystonia-parkinsonism is a rare movement disorder that is
      highly prevalent in Panay Island in the Philippines. Earlier studies identified
      seven different genetic alterations within a 427-kb disease locus on the X
      chromosome; however, the exact disease-causing variant among these is still not
      unequivocally determined. To further investigate the genetic cause of this
      disease, we sequenced all previously reported genetic alterations in 166 patients
      and 473 Filipino controls. Singly occurring variants in our ethnically matched
      controls would have allowed us to define these as polymorphisms, but none were
      found. Instead, we identified five patients carrying none of the disease
      associated variants, and one male control carrying all of them. In parallel, we
      searched for novel single-nucleotide variants using next-generation sequencing.
      We did not identify any shared variants in coding regions of the X chromosome.
      However, by validating intergenic variants discovered via genome sequencing, we
      were able to define the boundaries of the disease-specific haplotype and narrow
      the disease locus to a 294-kb region that includes four known genes. Using
      microarray-based analyses, we ruled out the presence of disease-linked copy
      number variants within the implicated region. Finally, we utilized in silico
      analysis and detected no strong evidence of regulatory regions surrounding the
      disease-associated variants. In conclusion, our finding of disease-specific
      variants occurring in complete linkage disequilibrium raises new insights and
      intriguing questions about the origin of the disease haplotype, the existence of
      phenocopies and of reduced penetrance, and the causative genetic alteration in
      XDP. 

PMID- 25604860
TI  - Comparison of antibiotic susceptibility in viridans group streptococci in low and
      high antibiotic-prescribing General Practices.
AB  - WHAT IS KNOWN AND OBJECTIVE: Antibiotic resistance has become a global public
      health issue. Most antibiotics are prescribed in the community, although there is
      less stewardship of such agents in the community compared to secondary and
      tertiary care. Few studies have attempted to examine the prescribing practices in
      General Practice and its impact on antibiotic resistance and, therefore, a study
      was performed in order to compare antibiotic susceptibilities of commensal
      viridans group streptococci (VGS) obtained from patient cohorts in General
      Practices (GP), who were high and low prescribers of oral antibiotics. METHOD:
      Sixty-five patients (<1 month-81 years; 77% female: 23% male) were enrolled onto
      the study, and viridans group streptococci (n = 5/patient) were collected from
      each patient's nasal passages and oropharynx region and tested for antibiotic
      susceptibility against (i) tetracyclines (doxycycline); (ii) macrolides
      (erythromycin); (iii) beta-lactams (penicillin G); and (iv) fluoroquinolones
      (ofloxacin & levofloxacin). RESULTS AND DISCUSSION: There were no significant
      differences in MICs between high and low GP prescribers with doxycycline (P =
      0.094), erythromycin (P = 0.122), ofloxacin (P = 0.193) and levofloxacin (P =
      0.058). However, there was a significant difference between high and low GP
      practices with regard to penicillin G (P = 0.031). This finding is important as
      the beta-lactams are the most commonly prescribed oral antibiotic in the
      community. WHAT IS NEW AND CONCLUSION: This study demonstrates that high
      prescribing practices may lead to an altered (higher) level of resistance to
      these agents in the commensal VGS population, which may be important as
      reservoirs of antibiotic resistance determinants in subsequent horizontal gene
      transfer events, particularly with newly colonizing pathogens, including
      pneumococci. Primary care physicians should be aware that increased prescribing
      of antibiotics may led to increased level of penicillin resistance.

PMID- 25604861
TI  - Single-nucleotide polymorphisms in one-carbon metabolism genes, Mediterranean
      diet and breast cancer risk: a case-control study in the Greek-Cypriot female
      population.
AB  - Single-nucleotide polymorphisms (SNPs) within genes of the one-carbon metabolism
      pathway have been shown to interact with dietary folate intake to modify breast
      cancer (BC) risk. Our group has previously demonstrated that the Mediterranean
      dietary pattern, rich in beneficial one-carbon metabolism micronutrients,
      protects against BC in Greek-Cypriot women. We aimed to investigate whether SNPs
      in the MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) genes modify the
      effect of the Mediterranean dietary pattern on BC risk. Dietary intake data were
      obtained using a 32-item food-frequency questionnaire. A dietary pattern specific
      to the Greek-Cypriot population, which closely resembles the Mediterranean diet,
      was derived using principal component analysis (PCA) and used as our dietary
      variable. Genotyping was performed on subjects from the MASTOS study, a case
      control study of BC in Cyprus, using TaqMan assays. Adjusted odds ratios (ORs)
      were estimated using logistic regression analyses. High adherence to the PCA
      derived Mediterranean dietary pattern further reduced BC risk with increasing
      number of variant MTHFR 677T alleles (ORQ4vs.Q1 for 677TT = 0.37, 95 % CI 0.20
      0.69, for 677 CT = 0.60, 95 % CI 0.42-0.86). Additionally, high adherence to the
      Mediterranean dietary pattern decreased BC risk in subjects with at least one MTR
      2756A allele (ORQ4vs.Q1 for 2756AA = 0.59, 95 % CI 0.43-0.81, for 2756AG = 0.59,
      95 % CI 0.39-0.91) and in subjects with the MTHFR 1298CC genotype (ORQ4vs.Q1
      0.44, 95 % CI 0.30-0.65). Overall P-interaction values, however, were not
      statistically significant. Our study suggests that these MTHFR and MTR SNPs may
      act as effect modifiers, highlighting their biological significance in the
      association between Mediterranean diet, the one-carbon metabolism pathway and BC.

PMID- 25604862
TI  - Comorbidity between lifetime eating problems and mood and anxiety disorders:
      results from the Canadian Community Health Survey of Mental Health and Well
      being.
AB  - This study was to examine profiles of eating problems (EPs), mood and anxiety
      disorders and their comorbidities; explore risk patterns for these disorders; and
      document differences in health service utilization in a national population. Data
      were from the Canadian Community Health Survey of Mental Health and Well-being.
      The lifetime prevalence of EPs was 1.70% among Canadians, compared with 13.25%
      for mood disorder, 11.27% for anxiety disorder and 20.16% for any mood or anxiety
      disorder. Almost half of those with EPs also suffered with mood or anxiety
      disorders. A similar pattern in depressive symptoms was found among individuals
      with major depression and EPs, but individuals with EPs reported fewer symptoms.
      Factors associated with the comorbidity of EPs and mood and anxiety disorders
      were identified. Individuals with EPs reported more unmet needs. Patients with
      EPs should be concomitantly investigated for mood and anxiety disorders, as
      similar interventions may be effective for both.

PMID- 25604863
TI  - Pathogenesis of human papillomavirus-associated mucosal disease.
AB  - Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix
      and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated
      neoplastic progression include persistent infection, deregulated expression of
      virus early genes in basal epithelial cells and genomic instability causing
      secondary host genomic imbalances. There are multiple mechanisms by which
      deregulated virus early gene expression may be achieved. Integration of virus DNA
      into host chromosomes is observed in the majority of cervical squamous cell
      carcinomas (SCCs), although in ~15% of cases the virus remains extrachromosomal
      (episomal). Interestingly, not all integration events provide a growth advantage
      to basal cervical epithelial cells or lead to increased levels of the virus
      oncogenes E6 and E7, when compared with episome-containing basal cells. The
      factors that provide a competitive advantage to some integrants, but not others,
      are complex and include virus and host contributions. Gene expression from
      integrated and episomal HRHPV is regulated through host epigenetic mechanisms
      affecting the virus long control region (LCR), which appear to be of functional
      importance. New approaches to treating HRHPV-associated mucosal neoplasia include
      knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition
      of virus early gene transcription through targeting or use of epigenetic
      modifiers. Copyright (c) 2014 Pathological Society of Great Britain and Ireland.
      Published by John Wiley & Sons, Ltd. 

PMID- 25604864
TI  - On the Social Constructionist Approach to Traumatized Selves in Post-disaster
      Settings: State-Induced Violence in Nandigram, India.
AB  - Through the use of concepts such as traumatization and posttraumatic stress
      disorder (PTSD), the distressing experiences of survivors are understood in
      psychology and psychiatry primarily as the behavioural symptoms resulting
      supposedly from an incomplete emotional and cognitive processing of traumatic
      events. Due to such an exclusive focus on the intra-psychic processes, besides
      the survivors' healing facilitated by cultural beliefs and symbols, their trauma
      related distress associated with the cultural interpretation of loss is also
      generally ignored. This paper illustrates the utility of the social
      constructionist paradigm in understanding the survivors' experiences of suffering
      and healing within the cultural and socio-political context of violence through
      an ethnographic study among the poor farmers of Nandigram, India, inflicted by
      violence from the state government as it tried to forcibly acquire their land to
      build a chemical factory. How the traumatized selves experience intense distress
      resulting from disruptions to a sense of wholeness and how this wholeness may be
      reformulated through culturally valued beliefs are highlighted in the themes of
      suffering ('experience of PTSD symptoms', 'betrayed self', 'overwhelmed by loss',
      and 'biographical disruption') and healing ('moral re-affirmation', 'sense of
      togetherness', 'sense of security due to change in political environment')
      presented in the vignettes. 

PMID- 25604865
TI  - Association of TGF-beta2 levels in breast milk with severity of breast biopsy
      diagnosis.
AB  - PURPOSE: TGF-beta plays a dual role in breast carcinogenesis, acting at early
      stages as tumor-suppressors and later as tumor-promoters. TGF-beta isoforms are
      expressed in breast tissues and secreted in milk, suggesting that analysis of
      levels in milk might be informative for breast cancer risk. Accordingly, we
      assessed TGF-beta2 levels in milk from women who had undergone a breast biopsy
      and related the concentrations to diagnosis. METHODS: Milk donated by women who
      had undergone or were scheduled for a breast biopsy was shipped on ice for
      processing and testing. Breast cancer risk factors were obtained through a self
      administered questionnaire, and biopsy diagnoses were extracted from pathology
      reports. TGF-beta2 levels in milk, assessed as absolute levels and in relation to
      total protein, were analyzed in bilateral samples donated by 182 women. Linear
      regression was used to estimate relationships of log-transformed TGF-beta2 levels
      and TGF-beta2/ total protein ratios to biopsy category. RESULTS: Milk TGF-beta2
      levels from biopsied and non-biopsied breasts within women were highly correlated
      (r (2) = 0.77). Higher mean TGF-beta2 milk levels (based on average of bilateral
      samples) were marginally associated with more severe breast pathological
      diagnosis, after adjusting for duration of nursing current child (adjusted p
      trend = 0.07). CONCLUSIONS: Our exploratory analysis suggests a borderline
      significant association between higher mean TGF-beta2 levels in breast milk and
      more severe pathologic diagnoses. Further analysis of TGF-beta signaling in milk
      may increase understanding of postpartum remodeling and advance efforts to
      analyze milk as a means of assessing risk of breast pathology.

PMID- 25604867
TI  - Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly
      increased by tocilizumab treatment in patients with rheumatoid arthritis:
      increase in regulatory T cells correlates with clinical response.
AB  - INTRODUCTION: Tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, is
      clinically effective against rheumatoid arthritis (RA), and several reports have
      indicated how TCZ influences a number of mechanisms underlying RA pathogenesis.
      However, it is still unclear whether TCZ affects inflammatory cells in peripheral
      blood and whether any such changes are associated with clinical response. We
      evaluated associations between proportions of subsets of peripheral immune cells
      and clinical response in patients with RA treated with TCZ. METHODS: Thirty-nine
      consecutive patients with RA who started to receive TCZ as their first biologic
      between March 2010 and April 2012 were enrolled. The proportions of several
      subsets of peripheral cells with their levels of expression of differentiation
      markers, activation markers and costimulatory molecules were measured
      sequentially from baseline to week 52 by flow cytometry analysis. RESULTS:
      Clinical Disease Activity Index (CDAI) remission was achieved in 53.8% of
      patients at week 52 of TCZ therapy. The proportions of CD4(+)CD25(+)CD127(low)
      regulatory T cells (Treg) and HLA-DR(+) activated Treg cells significantly
      increased with TCZ therapy (P < 0.001 and P < 0.001, respectively), whereas
      proportions of CD3(+)CD4(+)CXCR3(-)CCR6(+)CD161(+) T helper 17 cells did not
      change over the 52 weeks. The proportions of CD20(+)CD27(+) memory B cells, HLA
      DR(+)CD14(+) and CD69(+)CD14(+) activated monocytes, and CD16(+)CD14(+) monocytes
      significantly decreased (P < 0.001, P < 0.001, P < 0.001 and P < 0.001,
      respectively). Among them, only the change in Treg cells was inversely correlated
      with the change in CDAI score (rho = -0.40, P = 0.011). The most dynamic increase
      in Treg cells was observed in the CDAI remission group (P < 0.001). CONCLUSION:
      This study demonstrates that TCZ affected proportions of circulating immune cells
      in patients with RA. The proportion of Treg cells among CD4(+) cells correlated
      well with clinical response.

PMID- 25604868
TI  - Pattern recognition of neuron specific enolase and carcinoembryonic antigen in
      whole blood samples.
AB  - New tools and methods for pattern recognition of neuron specific enolase (NSE)
      and carcinoembryonic antigen (CEA) were proposed for the screening of whole blood
      samples. The new tools were based on stochastic sensors designed using nanoporous
      gold microspheres, graphite, graphene, diamond paste as well as alpha-CDs, and
      5,10,15,20-tetraphenyl-21H,23H-porphyrin. The best sensor for the assay of CEA
      was the one based on P/graphite (the limit of determination was 16 fg/ml and
      sensitivity was 2.32 * 10(7)  s mg(-1)  ml), while for the assay of NSE the, best
      sensor was the one based on P/graphene (the limit of determination was 7.45 pg/ml
      and sensitivity was 2.49 * 10(8)  s mg(-1)  ml). The sensor of choice for
      simultaneous detection of NSE and CEA is the one based on P/graphene because we
      need high sensitivity and low limit of determination for NSE. To our knowledge,
      this is the only one screening test for early detection of lung cancer, by
      identification of NSE and CEA in whole blood samples.

PMID- 25604866
TI  - Association between high-sensitivity C-reactive protein (hsCRP) and change in
      mammographic density over time in the SWAN mammographic density subcohort.
AB  - PURPOSE: High mammographic density (MD) is a strong risk factor for breast
      cancer. Chronic inflammation may be related to breast cancer risk through a
      mechanism involving the percent of breast area that is dense (percent MD).
      Longitudinal assessments, however, are lacking and thus were constructed to
      evaluate the relationship between chronic inflammation and percent MD. METHODS:
      We evaluated whether elevated (>3 mg/L) high-sensitivity C-reactive protein
      (hsCRP), a biomarker of inflammation, was associated with change in percent MD
      among 653 women aged 42-52 years at baseline in the Study of Women's Health
      Across the Nation, a longitudinal study of midlife women. We used a mixed model
      to analyze data from an average of 4.7 mammograms per woman collected during an
      average follow-up of 4.9 years (SD = 1.47). RESULTS: Elevated hsCRP at baseline
      was associated with lower baseline percent MD and a significantly slower annual
      decline over time of percent MD in an adjusted model that did not include body
      mass index (BMI) (beta = 0.88, 95 % CI 0.44, 1.31). This association was
      attenuated and nonsignificant when BMI was included in the model (beta = 0.37, 95
      % CI -0.09, 0.84). Elevated hsCRP levels over time (time-varying elevated hsCRP
      levels) were also associated with a significantly slower decline in percent MD
      (beta = 0.62, 95 % CI 0.30, 0.94). This association was attenuated, but still
      significant after adjusting for baseline BMI (beta = 0.40, 95 % CI 0.07, 0.73).
      CONCLUSION: These results suggest that inflammation may be related to slower
      reduction in percent MD.

PMID- 25604869
TI  - A pilot, exploratory report on dyadic interpersonal psychotherapy for perinatal
      depression.
AB  - Perinatal depression is a major public health burden impacting both mothers and
      their offspring. The purpose of this study was to develop and test the
      acceptability and feasibility of a novel psychotherapeutic intervention that
      integrates an evidence-based intervention for depression, interpersonal
      psychotherapy (IPT), with postpartum dyadic psychotherapy focused on emotional
      development in the context of the mother-infant relationship. Nine women between
      12 and 30 weeks gestation with Edinburgh Depression Scale (EDS) scores >12 were
      entered into treatment. Three out of nine women dropped out of the study after
      initiating treatment (one lost to follow-up antepartum; two lost to follow-up
      postpartum). Seven out of eight women (87 %) reported clinically significant
      improvements in EDS scores from baseline to 37-39 weeks gestation, and all women
      had clinically significant improvements at 12 months postpartum. A small
      randomized controlled trial is underway to further examine the feasibility and
      acceptability of the intervention. 

PMID- 25604870
TI  - Will oral antibiotics suffice in osteomyelitis?

PMID- 25604871
TI  - Recent mycotoxin survey data and advanced mycotoxin detection techniques reported
      from China: a review.
AB  - Mycotoxin contamination in agro-food systems has been a serious concern over the
      last few decades in China, where the Ministry of Health has set maximum limits
      for mycotoxins in different agro-products. Overall survey data show that
      aflatoxin contamination in infant cereals, edible oils, raw milk, ginger and its
      related products are far below Chinese regulatory limits. The absence of
      aflatoxin M1 contamination in infant milk powders indicates a high standard of
      control. Aflatoxins in liquorice roots and lotus seeds have been reported for the
      first time. For deoxynivalenol, high levels were found in wheat grown in the
      Yangtze Delta region, which is more prone to rainfall, supporting Fusarium
      infection. The emerging mycotoxins beauvericins and enniatins have been reported
      in the medicinal herbs in China. Ochratoxin A in wine was below the European
      Union regulatory limits, but fumonisins in maize need to be monitored and future
      regulatory control considered. Overall from all the survey data analysed in this
      review, it can be concluded that 92% of the samples analysed had mycotoxin levels
      below the Chinese regulatory limits. In terms of detection techniques in recent
      years, immuno-based assays have been developed largely due to their excellent
      sensitivity and ease of use. Assays targeting multiple mycotoxins like
      aflatoxins, ochratoxin A, zearalenone and deoxynivalenol have been reported using
      microarrays and suspension arrays targeting in particular maize, rice and
      peanuts. Aptamer-based assays against ochratoxin A and aflatoxins B1 and B2 have
      been developed involving fluorescence detection; and surface plasmon resonance
      immunosensors have been developed targeting wine, maize, wheat, wild rye, hay and
      peanut oil with high sensitivity (> 0.025 ng l(-1)). Commercialisation of these
      technologies is much needed for wider usage in the coming years.

PMID- 25604872
TI  - CORR Insights(r): Delayed Slipped Capital Femoral Epiphysis After Treatment of
      Femoral Neck Fracture in Children.

PMID- 25604873
TI  - Editorial comment: symposium: 2014 Bernese Hip Symposium.

PMID- 25604874
TI  - Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm.
AB  - BACKGROUND: Orthopaedic biomaterials are susceptible to biofilm formation. A
      novel lipid-based material has been developed that may be loaded with antibiotics
      and applied as an implant coating at point of care. However, this material has
      not been evaluated for antibiotic elution, biofilm inhibition, or in vivo
      efficacy. QUESTIONS/PURPOSES: (1) Do antibiotic-loaded coatings inhibit biofilm
      formation? (2) Is the coating effective in preventing biofilm in vivo? METHODS:
      Purified phosphatidylcholine was mixed with 25% amikacin or vancomycin or a
      combination of 12.5% of both. A 7-day elution study for coated titanium and
      stainless steel coupons was followed by turbidity and zone of inhibition assays
      against Staphylococcus aureus and Pseudomonas aeruginosa. Coupons were inoculated
      with bacteria and incubated 24 hours (N = 4 for each test group). Microscopic
      images of biofilm were obtained. After washing and vortexing, attached bacteria
      were counted. A mouse biofilm model was modified to include coated and uncoated
      stainless steel wires inserted into the lumens of catheters inoculated with a
      mixture of S aureus or P aeruginosa. Colony-forming unit counts (N = 10) and
      scanning electron microscopy imaging of implants were used to determine
      antimicrobial activity. RESULTS: Active antibiotics with colony inhibition
      effects were eluted for up to 6 days. Antibiotic-loaded coatings inhibited
      biofilm formation on in vitro coupons (log-fold reductions of 4.3 +/- 0.4 in S
      aureus and 3.1 +/- 0 for P aeruginosa in phosphatidylcholine-only coatings, 5.6
      +/- 0 for S aureus and 3.1 +/- 0 for P aeruginosa for combination-loaded
      coatings, 5.5 +/- 0.3 for S aureus in vancomycin-loaded coatings, and 3.1 +/- 0
      for P aeruginosa for amikacin-loaded coatings (p < 0.001 for all comparisons of
      antibiotic-loaded coatings against uncoated controls for both bacterial strains,
      p < 0.001 for comparison of antibiotic-loaded coatings against
      phosphatidylcholine only for S aureus, p = 0.54 for comparison of vancomycin
      versus combination coating in S aureus, P = 0.99 for comparison of antibiotic-
      and unloaded phosphatidylcholine coatings in P aeruginosa). Similarly, antibiotic
      loaded coatings reduced attachment of bacteria to wires in vivo (log-fold
      reduction of 2.54 +/- 0; p < 0.001 for S aureus and 0.83 +/- 0.3; p = 0.112 for P
      aeruginosa). CONCLUSIONS: Coatings deliver active antibiotics locally to inhibit
      biofilm formation and bacterial growth in vivo. Future evaluations will include
      orthopaedic preclinical models to confirm therapeutic efficacy. CLINICAL
      RELEVANCE: Clinical applications of local drug delivery coating could reduce the
      rate of implant-associated infections.

PMID- 25604875
TI  - Synthetic mesh improves shoulder function after intraarticular resection and
      prosthetic replacement of proximal humerus.
AB  - BACKGROUND: Shoulder function often is limited after tumor resection and
      endoprosthetic replacement of the proximal humerus. This is partly attributable
      to the inability to reliably reattach rotator cuff tendons to the prosthesis and
      achieve adequate shoulder capsule repair with a metallic prosthesis. An option to
      attain these goals is to use synthetic mesh for the reconstruction, although the
      value of this method has not been well documented in the literature.
      QUESTIONS/PURPOSES: We asked whether patients who had shoulder reconstruction
      using synthetic mesh had (1) better shoulder function; (2) improved ROM compared
      with shoulder reconstructions without mesh; and (3) more stable joints compared
      with those in patients with similar resections who had reconstructions without
      synthetic mesh. METHODS: During a 5-year period, we performed 41 intraarticular
      resections with endoprosthetic reconstructions for malignancies in the proximal
      humerus meeting specified criteria to generate similarity in the study groups.
      Twelve patients (29%) were lost to followup before 24 months, leaving 29 patients
      available for review at a mean of 45 months (range, 24-70 months). This
      retrospective study compared 14 patients with soft tissue reconstruction that
      included synthetic mesh with 15 patients with soft tissue reconstruction without
      the use of synthetic mesh. The choice was made during consultation between the
      patient and surgeon, after reviewing the perceived advantages and disadvantages
      of each approach. A tumor band (ligament advanced reinforcement system) was used
      as synthetic mesh and wrapped around the prosthesis of the proximal humerus for
      soft tissue reconstruction in the reconstruction-with-mesh group. Study endpoints
      included the Musculoskeletal Tumor Society (MSTS) function scores, American
      Shoulder and Elbow Surgeons (ASES) score, shoulder ROM, and proximal migration of
      the humeral prosthesis. RESULTS: The mean MSTS score for patients without
      synthetic mesh reconstruction was 20 +/- 3 points (66%), whereas for patients
      with synthetic mesh reconstruction, the mean score was 24 +/- 2 points (79%; p =
      0.001). Patients with synthetic mesh reconstruction had a higher mean total ASES
      score (85 +/- 1.1 points versus 72 +/- 1.7 points; p = 0.025), and better
      function for activities of daily living. They also had better ROM on mean active
      forward flexion (p = 0.020), abduction (p < 0.001), and external rotation (p <
      0.001) than patients without synthetic mesh reconstruction. Proximal migration of
      the prosthesis was observed in five of 15 of patients in the group without
      synthetic mesh reconstruction and in none of those treated with synthetic mesh (p
      = 0.042). CONCLUSIONS: Patients with intraarticular resection and endoprosthetic
      replacement of the proximal humerus with reconstruction that included synthetic
      mesh had better shoulder function and ROM, and more stable joints than patients
      who had reconstruction without synthetic mesh. This result supports prior
      observations by others and it remains to be shown whether use of the ligament
      advanced reconstruction system is superior to other types of mesh or other types
      of reconstructions. Further investigation is needed but our results indicate that
      using mesh should be considered for patients with tumor resection and
      endoprosthetic replacement of the proximal humerus.

PMID- 25604876
TI  - What is the effect of matrices on cartilage repair? A systematic review.
AB  - BACKGROUND: Articular cartilage has minimal endogenous ability to undergo repair.
      Multiple chondral restoration strategies have been attempted with varied results.
      QUESTIONS/PURPOSES: The purpose of our review was to determine: (1) Does
      articular chondrocyte transplantation or matrix-assisted articular chondrocyte
      transplantation provide better patient-reported outcomes scores, MRI morphologic
      measurements, or histologic quality of repair tissue compared with microfracture
      in prospective comparative studies of articular cartilage repair; and (2) which
      available matrices for matrix-assisted articular chondrocyte transplantation show
      the best patient-reported outcomes scores, MRI morphologic measurements, or
      histologic quality of repair tissue? METHODS: We conducted a systematic review of
      PubMed, CINAHL, and MEDLINE from March 2004 to February 2014 using keywords
      determined to be important for articular cartilage repair, including "cartilage",
      "chondral", "cell source", "chondrocyte", "matrix", "augment", "articular",
      "joint", "repair", "treatment", "regeneration", and "restoration" to find
      articles related to cell-based articular cartilage repair of the knee. The
      articles were reviewed by two authors (JDW, MKH), our study exclusion criteria
      were applied, and articles were determined to be relevant (or not) to the
      research questions. The Methodological Index for Nonrandomized Studies (MINORS)
      scale was used to judge the quality of nonrandomized manuscripts used in this
      review and the Jadad score was used to judge the quality of randomized trials.
      Seventeen articles were reviewed for the first research question and 83 articles
      were reviewed in the second research question from 301 articles identified in the
      original systematic search. The average MINORS score was 9.9 (62%) for
      noncomparative studies and 16.1 (67%) for comparative studies. The average Jadad
      score was 2.3 for the randomized studies. RESULTS: Articular chondrocyte
      transplantation shows better patient-reported outcomes at 5 years in patients
      without chronic symptoms preoperatively compared with microfracture (p = 0.026).
      Matrix-assisted articular chondrocyte transplantation consistently showed
      improved patient-reported functional outcomes compared with microfracture (p
      values ranging from < 0.001 to 0.029). Hyalograft C((r)) (Anika Therapeutics Inc,
      Bedford, MA, USA) and Chondro-gide((r)) (Genzyme Biosurgery, Kastrup, Denmark)
      are the matrices with the most published evidence in the literature, but no
      studies comparing different matrices met our inclusion criteria, because the
      literature consists only of uncontrolled case series. CONCLUSIONS: Matrix
      assisted articular chondrocyte transplantation leads to better patient-reported
      outcomes in cartilage repair compared with microfracture; however, future
      prospective research is needed comparing different matrices to determine which
      products optimize cartilage repair. LEVEL OF EVIDENCE: Level IV, therapeutic
      study.

PMID- 25604877
TI  - Premature Therapeutic Antimicrobial Treatments Can Compromise the Diagnosis of
      Late Periprosthetic Joint Infection.
AB  - BACKGROUND: In the absence of positive cultures and draining sinuses, the
      diagnosis of periprosthetic joint infection (PJI) relies on laboratory values. It
      is unknown if administration of antibiotics within 2 weeks before diagnostic
      evaluations can affect these tests in patients with PJI. QUESTIONS/PURPOSES: The
      purpose of this study was to investigate the correlation of antibiotic
      administration with (1) fluctuations in the synovial fluid and serology
      laboratory values; and (2) sensitivity of the diagnostic tests in patients with
      late PJI (per Musculoskeletal Infection Society [MSIS] criteria). METHODS:
      Synovial white blood cell (WBC) count, polymorphonuclear neutrophil (PMN)
      percentage, and serum erythrocyte sedimentation rate (ESR) and C-reactive protein
      (CRP) as well as culture results were investigated in 161 patients undergoing
      total knee arthroplasty with late PJI diagnosed with the MSIS criteria. Depending
      on whether presampling antibiotics were used, patients were divided in two groups
      (53 [33%] patients were on antibiotics). The median laboratory values and the
      false-negative rates were compared between the two groups. RESULTS: The median of
      all variables were lower in the antibiotic group compared with the other group:
      ESR (mm/hr): 70 versus 85, difference of medians (DOM) = 15 mm/hr, p = 0.018; CRP
      (mg/L): 72 versus 130, DOM = 58 mg/L, p = 0.038; synovial WBC (cells/MUL): 29,170
      versus 46,900, DOM = 17,730, p = 0.022; and synovial PMN%: 88.5% versus 92.5%,
      DOM = 4%, p = 0.012. Furthermore, using the MSIS cutoffs, the false-negative
      rates of several parameters were higher in the antibiotic group; ESR: 19.2% (nine
      of 47) versus 6.1% (six of 99) (relative risk, 3.1; 95% confidence interval [CI],
      1.2-8.3; p = 0.020); CRP: 14.9% (seven of 47) versus 2.00% (two of 100) (relative
      risk, 7.4; 95% CI, 1.6-34.4); PMN%: 23.1% (12 of 52) versus 9.4% (10 of 106)
      (relative risk, 2.4; 95% CI, 1.1-5.2; p = 0.027). Patients in the antibiotic
      group also had higher rates of negative cultures: 26.4% (14 of 53) versus 12.9%
      (14 of 108) (relative risk, 2.0; 95% CI, 1.05-3.9; p = 0.046). CONCLUSIONS: It
      appears that premature antibiotic treatments are associated with lower medians of
      diagnostic laboratory values. Thus, and in line with the guideline
      recommendations of the American Academy of Orthopaedic Surgeons, patients with
      suspected late-PJI should not receive antibiotics until the diagnosis is reached
      or refuted. LEVEL OF EVIDENCE: Level III, diagnostic study.

PMID- 25604878
TI  - Letter to the editor: Increased complication rates after hip and knee
      arthroplasty in patients with cirrhosis of the liver.

PMID- 25604879
TI  - CORR Insights(r): Spectroscopic and chromatographic quantification of an
      antioxidant-stabilized ultrahigh-molecular-weight polyethylene.

PMID- 25604882
TI  - A highly sensitive and recyclable SERS substrate based on Ag-nanoparticle
      decorated ZnO nanoflowers in ordered arrays.
AB  - Using a patterned sapphire substrate with a hemisphere array, flower-like ZnO
      nanorods grouped in a highly ordered array were fabricated on the wafer scale by
      routine solution growth. After decorating with high-density Ag nanoparticles
      (NPs), the ZnO nanoflower arrays were used as the substrates for surface enhanced
      Raman scattering (SERS). Using Rhodamine 6G as the probe molecules with a
      concentration down to 10(-10) M, the SERS substrates present an as high as 10(10)
      Raman enhancement with good reproducibility. The influence of Ag NP decoration on
      the SERS activity was explored and the sub-10 nm nanogaps between the adjacent Ag
      NPs were proved to be the primary electromagnetic "hot spots" responsible for the
      significant Raman enhancement. The Ag-NP-decorated ZnO nanoflower arrays were
      demonstrated to possess a self-cleaning function enabled by UV irradiation via
      photocatalytic degradation of the analyte molecules. In addition, the SERS
      substrate exhibited an extremely long service lifetime, possibly due to its
      superhydrophobicity and storage in the dark and a dry environment. 

PMID- 25604881
TI  - Hazard assessment of nitrosamine and nitramine by-products of amine-based CCS:
      alternative approaches.
AB  - Carbon capture and storage (CCS) technologies are considered vital and economic
      elements for achieving global CO2 reduction targets, and is currently introduced
      worldwide (for more information on CCS, consult for example the websites of the
      International Energy Agency (http://www.iea.org/topics/ccs/) and the Global CCS
      Institute (http://www.globalccsinstitute.com/)). One prominent CCS technology,
      the amine-based post-combustion process, may generate nitrosamines and their
      related nitramines as by-products, the former well known for their potential
      mutagenic and carcinogenic properties. In order to efficiently assess the
      carcinogenic potency of any of these by-products this paper reviews and discusses
      novel prediction approaches consuming less time, money and animals than the
      traditionally applied 2-year rodent assay. For this, available animal
      carcinogenicity studies with N-nitroso compounds and nitramines have been used to
      derive carcinogenic potency values, that were subsequently used to assess the
      predictive performance of alternative prediction approaches for these chemicals.
      Promising cancer prediction models are the QSARs developed by the Helguera group,
      in vitro transformation assays, and the in vivo initiation-promotion, and
      transgenic animal assays. All these models, however, have not been adequately
      explored for this purpose, as the number of N-nitroso compounds investigated is
      yet too limited, and therefore further testing with relevant N-nitroso compounds
      is needed. 

PMID- 25604880
TI  - Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein
      function in atherosclerotic rabbits.
AB  - Rosiglitazone has been found to have anti-atherogenic effects and to increase
      serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels. However, in vivo
      studies investigating the regulation of adenosine triphosphate-binding cassette
      transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) by
      rosiglitazone are limited. Moreover, the effects of rosiglitazone on the function
      and levels of HDL are unclear. In the present study, we investigated the effects
      of rosiglitazone on HDL function and its mechanisms of action in atherosclerotic
      rabbits. Our results revealed that rosiglitazone induced a significant increase
      in serum HDL-C levels, paraoxonase 1 (PON1) activity, [(3)H]cholesterol efflux
      rates, and the expression of ABCA1 and SR-BI in hepatocytes and peritoneal
      macrophages. The expression of ABCA1 was also increased in aortic lesions.
      Rosiglitazone markedly reduced serum myeloperoxidase (MPO) activity, aortic
      intima-media thickness (IMT) and the percentage of plaque area in the aorta. It
      can thus be concluded that in atherosclerotic rabbits, rosigitazone increases the
      levels of HDL-C and hinders atherosclerosis. Thus, it improves HDL quality and
      function, as well as the HDL-induced cholesterol efflux, exerting anti
      inflammatory and antioxidant effects.

PMID- 25604883
TI  - Phytochemical screening, total phenolic content and antioxidant activity of
      Byrsonima species.
AB  - The species of the Byrsonima genus (Malpighiaceae) have been used in folk
      medicine to treat gastrointestinal disorders, asthma and skin infections. In this
      study, the total phenolic content, antioxidant activity and phytochemical
      screening were carried out in polar extracts of Byrsonima coccolobifolia,
      Byrsonima verbascifolia and Byrsonima intermedia. The presence of tannins and
      flavonoids in the samples and high phenols content was observed. B.
      coccolobifolia and B. intermedia species showed the best results of antioxidant
      action. It was analysed the correlation between the methods, and there was a
      great correlation between phenolic content and antioxidant assay, showing that
      the phenolic substances contribute to the antioxidant activities of these plants.

PMID- 25604884
TI  - Long-term evaluation of the controlled pressure method for assessment of the
      vapor intrusion pathway.
AB  - Vapor intrusion (VI) investigations often require sampling of indoor air for
      evaluating occupant risks, but can be confounded by temporal variability and the
      presence of indoor sources. Controlled pressure methods (CPM) have been proposed
      as an alternative, but temporal variability of CPM results and whether they are
      indicative of impacts under natural conditions have not been rigorously
      investigated. This study is the first involving a long-term CPM test at a house
      having a multiyear high temporal resolution indoor air data set under natural
      conditions. Key observations include (a) CPM results exhibited low temporal
      variability, (b) false-negative results were not obtained, (c) the indoor air
      concentrations were similar to the maximum concentrations under natural
      conditions, and (d) results exceeded long-term average concentrations and
      emission rates under natural conditions by 1-2 orders of magnitude. Thus, the CPM
      results were a reliable indicator of VI occurrence and worst-case exposure
      regardless of day or time of year of the CPM test. 

PMID- 25604885
TI  - The intrauterine treatment of the retained foetal membrane in dairy goats by
      ozone: novel alternative to antibiotic therapy.
AB  - One of the major post-parturient complications in dairy goats is the retention of
      foetal membrane (RFM), which negatively influences their health, reproductive
      efficacy and welfare. The aim of this study was to compare the efficiency of
      intrauterine either ozone (OZ) or antibiotic (AB) treatments to establish the use
      of OZ as a novel and potential alternative to AB therapy in does with the RFM.
      The study was performed on 7 herds of dairy goats (n = 563) kept in the farms in
      Croatia. The conception rate was 563 of 641 total matings or 87.83%. The does
      from selected farms were observed during early puerperium and were divided into
      animals without the RFM (n = 522) and with the RFM (n = 41), treated either with
      foam spray OZ (n = 21) or with foaming AB oxytetracycline tablets (n = 20). The
      does with the RFM were mated successfully and became pregnant next kidding
      season, regardless of the treatment applied. Treatment with OZ attained similar
      results to the standard AB therapy, indicating that it could be novel potential
      alternative therapy of the RFM in dairy goats.

PMID- 25604886
TI  - Highly circularly polarized electroluminescence from a chiral europium complex.
AB  - The first circularly polarized OLED (CP-OLED) based on a chiral lanthanide
      complex is developed. With a simple architecture, this proof-of-concept device
      attains the highest polarization reported so far and additionally presents the
      first example of a Ln-based OLED that can be turned into a CP-OLED, fully
      retaining the special features of Ln-based OLEDs. 

PMID- 25604887
TI  - Pharmacokinetic and toxicity considerations in the use of neoadjuvant
      chemotherapy for bladder cancer.
AB  - INTRODUCTION: Neoadjuvant cisplatin-based combination chemotherapy remains the
      standard of care for surgically fit patients with muscle-invasive bladder cancer
      (MIBC). However, significant practice variability exists both in the use of
      neoadjuvant chemotherapy (NACT) and in the utilized regimens. AREAS COVERED: This
      review summarizes the available evidence on the pharmacokinetic, toxicology and
      efficacy considerations for determining appropriate neoadjuvant therapy in MIBC.
      This article consists of material obtained via PubMed, Medline and EMBASE
      literature searches up to November 2014. EXPERT OPINION: The role of NACT in MIBC
      cancer is well established. Common barriers to the successful use of NACT are the
      toxicities of therapy, the presence of underlying renal dysfunction, the time
      delay to definitive surgery and the potential for an inadequate treatment effect.
      The key finding from published NACT trials is that patients who successfully
      attain a complete pathologic response at the time of radical cystectomy can
      achieve durable long-term survivals. Although recent investigations into dose
      dense NACT regimens have provided intriguing results, alterations in dose
      intensity alone are unlikely to provide substantial clinical improvements.
      Further research into NACT should be directed towards the investigation of novel
      neoadjuvant therapies and to the evaluation of biomarkers predictive of complete
      pathologic response or decreased toxicities with standard cisplatin-based NACT.

PMID- 25604888
TI  - Remarkable diversity of intron-1 of the para voltage-gated sodium channel gene in
      an Anopheles gambiae/Anopheles coluzzii hybrid zone.
AB  - BACKGROUND: Genomic differentiation between Anopheles gambiae and Anopheles
      coluzzii--the major malaria vectors in sub-Saharan Africa--is localized into
      large "islands" toward the centromeres of chromosome-X and the two autosomes.
      Linkage disequilibrium between these genomic islands was first detected between
      species-specific polymorphisms within ribosomal DNA genes (IGS-rDNA) on the X
      chromosome and a single variant at position 702 of intron 1 (Int-1702) of the
      para Voltage-Gated Sodium Channel (VGSC) gene on chromosome arm 2 L. Intron-1
      sequence data from West and Central Africa revealed two clearly distinct and
      species-specific haplogroups, each characterized by very low polymorphism, which
      has been attributed to a selective sweep. The aim of this study was to analyse
      Int-1 sequence diversity in A. gambiae and A. coluzzii populations from the Far
      West of their range, in order to assess whether this selective-sweep signature
      could persist in a zone of high interspecific hybridization. METHODS: A 531 bp
      region of VGSC Int-1 was sequenced in 21 A. coluzzii, 31 A. gambiae, and 12
      hybrids from The Gambia and Guinea Bissau, located within the Far-West
      geographical region, and in 53 A. gambiae s.l. samples from the rest of the
      range. RESULTS: Far-West samples exhibit dramatic Int-1 polymorphism, far higher
      within each country than observed throughout the rest of the species range.
      Moreover, patterning of haplotypes within A. coluzzii confirms previous evidence
      of a macro-geographic subdivision into a West and a Central African genetic
      cluster, and reveals a possible genetic distinction of A. coluzzii populations
      from the Far-West. CONCLUSIONS: The results suggest a relaxation of selective
      pressures acting across the VGSC gene region in the hybrid zone. Genetic
      differentiation in the Far-West could be attributable to a founder effect within
      A. coluzzii, with subsequent extensive gene flow with secondarily-colonizing A.
      gambiae, potentially yielding a novel insight on the dynamic processes impacting
      genetic divergence of these key malaria vectors.

PMID- 25604889
TI  - Identification of novel viral receptors with cell line expressing viral receptor
      binding protein.
AB  - The viral cell receptors and infection can be blocked by the expression of the
      viral receptor-binding protein. Thus, the viral cell receptor is an attractive
      target for anti-viral strategies, and the identification of viral cell receptor
      is critical for better understanding and controlling viral disease. As a model
      system for viral entry and anti-retroviral approaches, avian sarcoma/leukosis
      virus (ASLV, including the A-J ten subgroups) has been studied intensively and
      many milestone discoveries have been achieved based on work with ASLV. Here, we
      used a DF1 cell line expressed viral receptor-binding protein to efficiently
      identify chicken Annexin A2 (chANXA2) as a novel receptor for retrovirus ALV-J
      (avian leukosis virus subgroup J). Our data demonstrate that antibodies or siRNA
      to chANXA2 significantly inhibited ALV-J infection and replication, and over
      expression of chANXA2 permitted the entry of ALV-J into its non-permissible
      cells. Our findings have not only identified chANXA2 as a novel biomarker for
      anti-ALV-J, but also demonstrated that cell lines with the expression of viral
      receptor-binding protein could be as efficient tools for isolating functional
      receptors to identify novel anti-viral targets. 

PMID- 25604890
TI  - "The usual suspects"- analysis of transcriptome sequences reveals deviating B
      gene activity in C. vulgaris bud bloomers.
AB  - BACKGROUND: The production of heather (Calluna vulgaris) in Germany is highly
      dependent on cultivars with mutated flower morphology, the so-called diplocalyx
      bud bloomers. So far, this unique flower type of C. vulgaris has not been
      reported in any other plant species. The flowers are characterised by an
      extremely extended flower attractiveness, since the flower buds remain closed
      throughout the complete flowering season. The flowers of C. vulgaris bud bloomers
      are male sterile, because the stamens are absent. Furthermore, petals are
      converted into sepals. Therefore the diplocalyx bud bloomer flowers consist of
      two whorls of sepals directly followed by the gynoecium. RESULTS: A broad
      comparison was undertaken to identify genes differentially expressed in the bud
      flowering phenotype and in the wild type of C. vulgaris. Transcriptome sequence
      reads were generated using 454 sequencing of two flower type specific cDNA
      libraries. In total, 360,000 sequence reads were obtained, assembled to 12,200
      contigs, functionally mapped, and annotated. Transcript abundances were compared
      and 365 differentially expressed genes detected. Among these differentially
      expressed genes, Calluna vulgaris PISTILLATA (CvPI) which is the orthologue of
      the Arabidopsis B gene PISTILLATA (PI) was considered as the most promising
      candidate gene. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT
      PCR) was performed to analyse the gene expression levels of two C. vulgaris B
      genes CvPI and Calluna vulgaris APETALA 3 (CvAP3) in both flower types. CvAP3
      which is the orthologue of the Arabidopsis B gene APETALA 3 (AP3) turned out to
      be ectopically expressed in sepals of wild type and bud bloomer flowers. CvPI
      expression was proven to be reduced in the bud blooming flowers. CONCLUSIONS:
      Differential expression patterns of the B-class genes CvAP3 and CvPI were
      identified to cause the characteristic morphology of C. vulgaris flowers leading
      to the following hypotheses: ectopic expression of CvAP3 is a convincing
      explanation for the formation of a completely petaloid perianth in both flower
      types. In C. vulgaris, CvPI is essential for determination of petal and stamen
      identity. The characteristic transition of petals into sepals potentially depends
      on the observed deficiency of CvPI and CvAP3 expression in bud blooming flowers.

PMID- 25604892
TI  - A test of the central-marginal hypothesis using population genetics and
      ecological niche modelling in an endemic salamander (Ambystoma barbouri).
AB  - The central-marginal hypothesis (CMH) predicts that population size, genetic
      diversity and genetic connectivity are highest at the core and decrease near the
      edges of species' geographic distributions. We provide a test of the CMH using
      three replicated core-to-edge transects that encompass nearly the entire
      geographic range of the endemic streamside salamander (Ambystoma barbouri). We
      confirmed that the mapped core of the distribution was the most suitable habitat
      using ecological niche modelling (ENM) and via genetic estimates of effective
      population sizes. As predicted by the CMH, we found statistical support for
      decreased genetic diversity, effective population size and genetic connectivity
      from core to edge in western and northern transects, yet not along a southern
      transect. Based on our niche model, habitat suitability is lower towards the
      southern range edge, presumably leading to conflicting core-to-edge genetic
      patterns. These results suggest that multiple processes may influence a species'
      distribution based on the heterogeneity of habitat across a species' range and
      that replicated sampling may be needed to accurately test the CMH. Our work also
      emphasizes the importance of identifying the geographic range core with methods
      other than using the Euclidean centre on a map, which may help to explain
      discrepancies among other empirical tests of the CMH. Assessing core-to-edge
      population genetic patterns across an entire species' range accompanied with ENM
      can inform our general understanding of the mechanisms leading to species'
      geographic range limits. 

PMID- 25604891
TI  - Different strategies for diagnosing gestational diabetes to improve maternal and
      infant health.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is carbohydrate intolerance
      resulting in hyperglycaemia with onset or first recognition during pregnancy. If
      untreated, perinatal morbidity and mortality may be increased. Accurate diagnosis
      allows appropriate treatment. Use of different tests and different criteria will
      influence which women are diagnosed with GDM. OBJECTIVES: To evaluate and compare
      different testing strategies for diagnosis of gestational diabetes mellitus to
      improve maternal and infant health while assessing their impact on healthcare
      service costs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (31 October 2014) and reference lists of retrieved
      studies. SELECTION CRITERIA: We included randomised trials if they evaluated
      tests carried out to diagnose GDM. We excluded studies that used a quasi-random
      model. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trials for inclusion and risk of bias, extracted data and checked them for
      accuracy. MAIN RESULTS: We identified six small trials, including 694 women.
      These trials were assessed as having varying risk of bias, with few outcomes
      reported. We prespecified six outcomes to be assessed for quality using the GRADE
      (Grades of Recommendation, Assessment, Development and Evaluation) approach; data
      for only one outcome (diagnosis of gestational diabetes) were available for
      assessment. One trial compared three different methods of delivering glucose: a
      candy bar (39 women), a 50-gram glucose polymer drink (40 women) and a 50-gram
      glucose monomer drink (43 women). We have reported results reported by this trial
      as separate comparisons. 75-gram oral glucose tolerance test (OGTT) versus 100
      gram OGTT (one trial, 248 women): Women given the 75-gram OGTT had a higher
      relative risk of being diagnosed with GDM (risk ratio (RR) 2.55, 95% confidence
      interval (CI) 0.96 to 6.75). This difference was borderline in terms of
      statistical significance, and evidence was considered to be of very low quality
      when assessed by GRADE. No data were reported for the following additional
      outcomes prespecified for assessment in GRADE: caesarean section, macrosomia >
      4.5 kg or however defined in the trial, long-term type 2 diabetes maternal, long
      term type 2 diabetes infant and economic costs. Candy bar versus 50-gram glucose
      monomer drink (one trial, 60 women): More women receiving the candy bar, rather
      than glucose monomer, preferred the taste of the candy bar (RR 0.60, 95% CI 0.42
      to 0.86). Infant outcomes were not reported. 50-gram glucose polymer drink versus
      50-gram glucose monomer drink (three trials, 239 women): Mean difference (MD) in
      gestation at birth was -0.80 weeks (one trial, 100 women; 95% CI -1.69 to 0.09).
      Total side effects were less common with the glucose polymer drink (one trial, 63
      women; RR 0.21, 95% CI 0.07 to 0.59), and no clear difference in taste
      acceptability was reported (one trial, 63 women; RR 0.99, 95% CI 0.76 to 1.29).
      Significantly fewer women reported nausea following the 50-gram glucose polymer
      drink compared with the 50-gram glucose monomer drink (one trial, 66 women; RR
      0.29, 95% CI 0.11 to 0.78). No other measures of maternal morbidity or outcomes
      for the infant were reported. 50-gram glucose food versus 50-gram glucose drink
      (one trial, 30 women): Women receiving glucose in their food, rather than as a
      drink, reported fewer side effects (RR 0.08, 95% CI 0.01 to 0.56). No clear
      difference was noted in the number of women requiring further testing (RR 0.14,
      95% CI 0.01 to 2.55). No other measures of maternal morbidity or outcome were
      reported for the infant. 75-gram oral glucose tolerance test (OGTT) World Health
      Organization (WHO) criteria versus 75-gram OGTT American Diabetes Association
      (ADA) criteria (one trial, 116 women): No clear differences in included outcomes
      were observed between women who received the 75-gram OGTT and were diagnosed
      using criteria based on WHO (1999) recommendations and women who received the 75
      gram OGTT and were diagnosed using criteria recommended by the ADA (1979).
      Outcomes measured included diagnosis of gestational diabetes (RR 1.47, 95% CI
      0.66 to 3.25), caesarean birth (RR 1.07, 95% CI 0.85 to 1.35), macrosomia defined
      as > 90th percentile by ultrasound or birthweight equal to or exceeding 4000 g
      (RR 0.73, 95% CI 0.19 to 2.79), stillbirth (RR 0.49, 95% CI 0.02 to 11.68) and
      instrumental birth (RR 0.21, 95% CI 0.01 to 3.94). AUTHORS' CONCLUSIONS: Evidence
      is insufficient to permit assessment of which strategy is best for diagnosing
      GDM.

PMID- 25604893
TI  - Prevalence and incidence of clinically recognized cases of Type 1 diabetes in
      children and adolescents in Rwanda, Africa.
AB  - AIMS: To determine prevalence and incidence estimates for clinically recognized
      cases of Type 1 diabetes from the Life For a Child Program (LFAC) with onset < 26
      years in six representative districts, and the capital, of Rwanda. METHODS: Cases
      were identified from the LFAC registry and visits to district hospitals.
      Denominators were calculated from district-level population surveys. Period
      prevalence data were collected from 1 August 2011 to 31 July 2012 and annual
      incidence rates were calculated, retrospectively, for 2004-2011. Ninety-five per
      cent confidence intervals (95% CI) were calculated using a Poisson distribution.
      RESULTS: The prevalence of known Type 1 diabetes in seven districts in Rwanda for
      ages < 26 years was 16.4 [95% CI 14.6-18.4]/100 000 and for < 15 years was 4.8
      [3.5-6.4]/100 000. Prevalence was higher in females (18.5 [15.8-21.4]/100 000)
      than males (14.1 [11.8-16.7]/100 000; P = 0.01) and rates increased with age. The
      annual incidence rate for those < 26 years was stable between 2007 and 2011 with
      a mean incidence over that time of 2.7 [2.0-3.7]/100 000 ( < 15 years = 1.2 [0.5
      2.0]/100 000). Incidence rates were higher in females than males and peaked in
      males at ages 17 and 22 years and in females at age 18 years. CONCLUSIONS: Our
      report of known Type 1 diabetes cases shows lower incidence and prevalence rates
      in Rwanda than previously reported in the USA and most African countries.
      Incidence of recognized cases has increased over time, but has recently
      stabilized. However, the likelihood of missed cases due to death before diagnosis
      and misdiagnosis is high and therefore more definitive studies are needed.

PMID- 25604894
TI  - Impact of growth hormone (GH) and follicle stimulating hormone (FSH) on in vitro
      canine preantral follicle development and estradiol production.
AB  - OBJECTIVE: Evaluate the effect of different concentrations of growth hormone (GH)
      on the in vitro development of domestic dog (Canis lupus familiaris) preantral
      follicles in the presence or absence of follicle stimulating hormone (FSH).
      METHODS: Secondary preantral follicles, isolated by microdissection, were
      cultured in a medium composed of alphaMEM with bovine serum albumin (BSA),
      glutamine, hypoxanthine, insulin, transferrin, selenium and ascorbic acid
      (alphaMEM(+)-control) added at different concentrations of GH (GH10 ng/ml or GH50
      ng/ml) and FSH (GH10+FSH, GH50+FSH). Follicle development was evaluated based on
      the percentage of intact follicles, antrum formation, follicular diameter,
      follicular viability using fluorescent markers and estradiol production. RESULTS:
      GH50 was the only treatment that maintained the same percentage of normal
      morphologically follicles from day 0 to day 18 of culture (P<0.05). For all
      treatments, except the control, follicles were viable throughout the 18 days of
      culture (P<0.05). GH50 supplemented with FSH (GH50+FSH) resulted in the highest
      average follicular diameter (P<0.05) from day 12 to 18. Follicles from both the
      control and the GH50+FSH treatment groups actively and increasingly secreted
      estradiol from day 6 to 18 of culture (P<0.05). CONCLUSIONS: Our study
      demonstrates that GH benefits the maintenance of follicular morphology in a dose
      dependent manner and, in association with FSH, stimulates in vitro follicular
      growth and estradiol production.

PMID- 25604895
TI  - Structure of the Elongator cofactor complex Kti11/Kti13 provides insight into the
      role of Kti13 in Elongator-dependent tRNA modification.
AB  - Modification of wobble uridines of many eukaryotic tRNAs requires the Elongator
      complex, a highly conserved six-subunit eukaryotic protein assembly, as well as
      the Killer toxin-insensitive (Kti) proteins 11-14. Kti11 was additionally shown
      to be implicated in the biosynthesis of diphthamide, a post-translationally
      modified histidine of translation elongation factor 2. Recent data indicate that
      iron-bearing Kti11 functions as an electron donor to the [4Fe-4S] cluster of
      radical S-Adenosylmethionine enzymes, triggering the subsequent radical reaction.
      We show here that recombinant yeast Kti11 forms a stable 1 : 1 complex with
      Kti13. To obtain insights into the function of this heterodimer, the Kti11/Kti13
      complex was purified to homogeneity, crystallized, and its structure determined
      at 1.45 A resolution. The importance of several residues mediating complex
      formation was confirmed by mutagenesis. Kti13 adopts a fold characteristic of
      RCC1-like proteins. The seven-bladed beta-propeller consists of a unique mixture
      of four- and three-stranded blades. In the complex, Kti13 orients Kti11 and
      restricts access to its electron-carrying iron atom, constraining the electron
      transfer capacity of Kti11. Based on these findings, we propose a role for Kti13,
      and discuss the possible functional implications of complex formation. DATABASE:
      Structural data have been submitted to the Protein Data Bank under accession
      number 4X33.

PMID- 25604896
TI  - Lithium imide synergy with 3d transition-metal nitrides leading to unprecedented
      catalytic activities for ammonia decomposition.
AB  - Alkali metals have been widely employed as catalyst promoters; however, the
      promoting mechanism remains essentially unclear. Li, when in the imide form, is
      shown to synergize with 3d transition metals or their nitrides TM(N) spreading
      from Ti to Cu, leading to universal and unprecedentedly high catalytic activities
      in NH3 decomposition, among which Li2NH-MnN has an activity superior to that of
      the highly active Ru/carbon nanotube catalyst. The catalysis is fulfilled via the
      two-step cycle comprising: 1) the reaction of Li2NH and 3d TM(N) to form ternary
      nitride of LiTMN and H2, and 2) the ammoniation of LiTMN to Li2NH, TM(N) and N2
      resulting in the neat reaction of 2 NH3?N2+3 H2. Li2NH, as an NH3 transmitting
      agent, favors the formation of higher N-content intermediate (LiTMN), where Li
      executes inductive effect to stabilize the TM-N bonding and thus alters the
      reaction energetics.

PMID- 25604899
TI  - Sale and provision of injectable contraceptives in drug shops in developing
      countries: conclusions from a technical consultation.

PMID- 25604898
TI  - A study of the clinical and radiological features in a cohort of 93 patients with
      a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related
      phenotype.
AB  - Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that
      are commonly associated with orthopedic, ocular, and hearing problems. However,
      the frequency of many clinical features has never been determined. We
      retrospectively investigated the clinical, radiological, and genotypic data in a
      group of 93 patients with molecularly confirmed SEDC or a related disorder. The
      majority of the patients (80/93) had short stature, with radiological features of
      SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7),
      spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The
      remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or
      multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic
      surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid
      hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid
      hypoplasia and short stature was observed. Atlanto-axial instability, was
      observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension
      films of the cervical spine were available; however, it was rarely accompanied by
      myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had
      occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years).
      Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17
      required hearing aids. The ophthalmological features and possibly also hearing
      loss are often relatively frequent and severe in patients with splicing
      mutations. Based on clinical findings, age at onset and genotype-phenotype
      correlations in this cohort, we propose guidelines for the management and follow
      up in this group of disorders.

PMID- 25604900
TI  - Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone
      containing combined oral contraceptive: I. Endocrine effects.
AB  - OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels.
      This study investigated restoration of T and other androgen concentrations during
      COC use by 'co-administration' of dehydroepiandrosterone (DHEA). STUDY DESIGN: In
      this randomized, double-blind, placebo-controlled study in 99 new COC starters
      (18-35 years old with body mass index range 18-34 kg/m2), a COC containing 30mcg
      ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3cycles, followed
      by 6cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total
      T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Delta4
      androstenedione (AD), 3alpha-androstanediol glucuronide (ADG) and estradiol (E2)
      were measured, whereas free T and the free T index (FTI) were calculated.
      Assessments took place at baseline (no COC use), after the run-in period (COC use
      alone) and during the treatment period (DHEA or placebo). RESULTS: During COC use
      alone, androgen levels decreased, especially total T by 62% and free T by 86%,
      and SHBG increased by 243%. Total T increased with DHEA compared to placebo
      (change from end of run-in period to end of treatment period -- 1.3+/-1.2 nmol/L
      vs. 0.0+/-0.4 nmol/L; p<.0001) -- and was restored to baseline levels. Free T and
      the FTI increased significantly (p<.0001), but the free T level was still 53%
      below baseline levels. DHEA-S, AD and ADG increased significantly to levels above
      baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2.
      CONCLUSIONS: An EE/DRSP containing COC strongly suppressed endogenous androgen
      concentrations in all users. The addition of 50 mg DHEA to a COC regimen
      containing EE/DRSP restored total T to baseline levels, but free T levels were
      restored by only 47% as most of the T remains bound to SHBG. IMPLICATIONS: When
      using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is
      insufficient to normalize free T levels completely.

PMID- 25604902
TI  - Synovial infiltration in human T lymphotropic virus type I-associated adult T
      cell leukemia/lymphoma.

PMID- 25604901
TI  - Novel monoclonal antibodies to study tissue regeneration in planarians.
AB  - BACKGROUND: Planarians are an attractive model organism for studying stem cell
      based regeneration due to their ability to replace all of their tissues from a
      population of adult stem cells. The molecular toolkit for planarian studies
      currently includes the ability to study gene function using RNA interference
      (RNAi) and observe gene expression via in situ hybridizations. However, there are
      few antibodies available to visualize protein expression, which would greatly
      enhance analysis of RNAi experiments as well as allow further characterization of
      planarian cell populations using immunocytochemistry and other immunological
      techniques. Thus, additional, easy-to-use, and widely available monoclonal
      antibodies would be advantageous to study regeneration in planarians. RESULTS: We
      have created seven monoclonal antibodies by inoculating mice with formaldehyde
      fixed cells isolated from dissociated 3-day regeneration blastemas. These
      monoclonal antibodies can be used to label muscle fibers, axonal projections in
      the central and peripheral nervous systems, two populations of intestinal cells,
      ciliated cells, a subset of neoblast progeny, and discrete cells within the
      central nervous system as well as the regeneration blastema. We have tested these
      antibodies using eight variations of a formaldehyde-based fixation protocol and
      determined reliable protocols for immunolabeling whole planarians with each
      antibody. We found that labeling efficiency for each antibody varies greatly
      depending on the addition or removal of tissue processing steps that are used for
      in situ hybridization or immunolabeling techniques. Our experiments show that a
      subset of the antibodies can be used alongside markers commonly used in planarian
      research, including anti-SYNAPSIN and anti-SMEDWI, or following whole-mount in
      situ hybridization experiments. CONCLUSIONS: The monoclonal antibodies described
      in this paper will be a valuable resource for planarian research. These
      antibodies have the potential to be used to better understand planarian biology
      and to characterize phenotypes following RNAi experiments. In addition, we
      present alterations to fixation protocols and demonstrate how these changes can
      increase the labeling efficiencies of antibodies used to stain whole planarians.

PMID- 25604903
TI  - The effects of intravenous, glucose versus saline on ovarian follicles and their
      levels of some mediators of insulin signalling.
AB  - BACKGROUND: A short-term increase in food intake and specifically dietary energy
      can stimulate folliculogenesis and increase ovulation rate in ewes. The mechanism
      appears to involve the insulin-glucose metabolic system and its interaction with
      FSH signalling pathways in the granulosa cells of ovarian follicles. This
      experiment was designed to investigate the interaction between these two systems
      in the granulosa cells of ovarian follicles. METHODS: Thirty six Ile-de-France
      ewes were used in this controlled experiment to study the effects of intravenous
      glucose on folliculogenesis. Eighteen ewes were infused with glucose (10 mM/h for
      72 h) from day 8 of the oestrous cycle, while the others (controls) received
      saline. Ovaries were collected when the infusions ended (luteal phase) or 30 h
      later and after a luteolytic dose of a PGF2alpha analogue (follicular phase).
      Follicles were dissected and granulosa cells and follicular fluid harvested. The
      blood concentrations of glucose, insulin, oestradiol and FSH were monitored over
      the experiment. The levels of Aromatase P450 and of the phosphorylated and non
      phosphorylated forms of Akt, AMPK and ERK in granulosa cells and the
      concentration of oestradiol in follicular fluid, were determined. RESULTS:
      Glucose increased the circulating concentration of glucose (P < 0.05) and insulin
      (P < 0.05). It also increased the total number of follicles >1.0 mm in diameter
      (P < 0.05) and small (P < 0.05) follicles (>1.0 to 2.0 mm in diameter) but not
      medium (>2.0 to 3.5 mm in diameter) or large (>3.5 mm in diameter) follicles.
      Glucose decreased circulating oestradiol (P < 0.05) but not that of FSH or
      progesterone. Glucose reduced aromatase P450 (P < 0.05) and decreased the
      phosphorylation of Akt (P < 0.05), ERK (P < 0.05) and AMPK (P < 0.05) in
      granulosa cells from oestrogenic follicles. The level of Aromatase P450 was
      greatest in large oestrogenic follicles and the phosphorylation of Akt (P <
      0.05), ERK (P < 0.05) and AMPK (P < 0.05) was lower in small follicles compared
      to medium and large follicles. CONCLUSIONS: These data suggest that the effect of
      glucose in small follicles is a direct action of glucose that increases the
      number of small follicles while the effect of glucose in oestrogenic follicles is
      an indirect insulin-mediated action.

PMID- 25604904
TI  - A worksite intervention to reduce the cardiovascular risk: proposal of a study
      design easy to integrate within Italian organization of occupational health
      surveillance.
AB  - BACKGROUND: Despite the substantial amount of knowledge on effectiveness of
      worksite health promotion (WHP) in reducing cardiovascular disease (CVD) risk,
      WHP programs are not systematically applied in Italy. The aim was to design an
      intervention easy to integrate within the Italian organization of workplace
      health surveillance. METHODS: We used the "pretest-posttest design". Workers were
      employed in multiple occupations and resident in Veneto region, Italy.
      Occupational physicians (OPs) performed all examinations, including laboratory
      evaluation (capillary blood sampling and measure of glycaemia and cholesterolemia
      with portable devices), during the normal health surveillance at worksite. CVD
      risk was computed based on sex, age, smoking habit, diabetes, systolic pressure
      and cholesterol level. After excluding those with <40 years of age, missing
      consent, CVD diagnosis or current therapy for CVD, missing information, CVD risk
      <5%, out of 5,536 workers 451 underwent the intervention and 323 male workers
      were re-examined at 1 year. CVD risk was the most compelling argument for
      changing lifestyle. The counseling was based on the individual risk factors.
      Individuals examined at posttest were a small fraction of the whole (6% =
      323/5,536). In these workers we computed the ratio pretest/posttest of
      proportions (such as percent of subjects with cardiovascular risk >5%) as well as
      the exact McNemar significance probability or the exact test of table symmetry.
      RESULTS: CVD risk decreased by 24% (McNemar p = 0.0000) after the intervention;
      in a sensitivity analysis assuming that all subjects lost to follow-up kept their
      pretest cardiovascular risk value, the effect (-18%) was still significant
      (symmetry p < 0.0000). Each prevented CVD case was expected to cost about 5,700
      euro. CONCLUSIONS: The present worksite intervention promoted favorable changes
      of CVD risk that were reasonably priced and consistent across multiple
      occupations.

PMID- 25604906
TI  - Detection and localization of deep endometriosis by means of MRI and correlation
      with the ENZIAN score.
AB  - PURPOSE: To determine the accuracy of ENZIAN score, as detected on MR imaging,
      compared to surgical-pathologic findings. MATERIALS AND METHODS: This
      retrospective study was approved by the investigational review board and the
      requirement for informed patient consent was waived. 115 patients were included
      according to following criteria: tubo-ovarian and/or deep endometriosis suspected
      at physical examination and transvaginal ultrasound; availability of MR
      examination; histopathological results from laparoscopic or surgical treatment.
      EXCLUSION CRITERIA: lack of available MR examination, and/or (b) lack of a
      definitive histopathological results. Histopathological findings from bioptic
      specimens obtained during laparoscopic or laparotomic treatment were considered
      as reference standard. For all detected lesions a score according to ENZIAN score
      (revised 2010) was assigned both for MRI and histopathological findings. By
      comparing MRI-ENZIAN score and histopathological-ENZIAN score the overall
      sensitivity, specificity, accuracy, positive and negative predictive values in
      relation to presence/absence of deep endometriosis in each patient were
      calculated. k-Cohen to evaluate the degree of concordance between MRI-ENZIAN
      score and histopathological-ENZIAN score was also measured. Moreover the
      sensitivity, specificity, accuracy, positive and negative predictive values for
      each specific localization provided by ENZIAN score were also calculated.
      RESULTS: At histopathology, the diagnosis of deep endometriosis was confirmed in
      82/115 (71.3%) patients. The sensitivity, specificity, accuracy, PPV and NPV of
      MRI were 94%, 97%, 95%, 99%, 86%, respectively. The highest accuracy was for
      adenomyosis (100%) and endometriosis of utero-sacral ligaments (USLs) (98%),
      slightly lower for vagina-rectovaginal septum an colo-rectal walls (96%), and the
      lowest for bladder endometriosis (92%). The concordance between histopathological
      and MRI ENZIAN score was excellent (k=0.824); in particular it was 0.812 for
      lesions in vagina-rectovaginal space, 0.890 for lesions in USL, 0.822 for lesions
      in rectum-sigmoid colon, 1.000 for uterine adenomyosis, and 0.367 for lesions
      located in the bladder wall. CONCLUSION: MRI correlates with the ENZIAN score and
      has an accuracy of 95% in the detection and localization of deep endometriosis,
      allowing to minimize false negative results (4%) in patients with deep
      endometriosis and to obtain a correct preoperative staging.

PMID- 25604907
TI  - Comparison of 3.0 T magnetic resonance imaging and X-ray mammography in the
      measurement of ductal carcinoma in situ: a comparison with histopathology.
AB  - PURPOSE: To determine if MRI data obtained at 3.0 T can more accurately report
      the size of DCIS as compared to radiographic mammography, as a whole cohort and
      when subdivided by lesion characteristics. METHODS: Thirty-nine participants
      underwent X-ray mammography and MRI prior to breast surgery for DCIS. Longest
      diameter (LD) measurements were recorded for each imaging modality and compared
      to histopathological LD via a logarithmic transformed Bland-Altman agreement plot
      methodology resulting in dimensionless mean difference and 95% limits of
      agreement (LoA). RESULTS: Data from 39 patients with a median age of 55 years
      (range 38-78 years) underwent analysis. Mastectomy was undertaken in 21 cases,
      while breast conserving surgery was performed in 18 subjects. Histopathological
      analysis revealed one low grade, nine intermediate grade, and 21 high grade
      lesions. The mean+/-standard deviation LD measurements for histopathology, X-ray
      mammography and MRI were 50.6+/-34.2 mm, 30.7+/-23.1 mm and 49.6+/-26.8 mm
      respectively. Bland-Altman agreement plot analysis for the whole cohort revealed
      not only a smaller logarithmic mean difference between MRI and histopathology
      (0.086), but also narrower 95% LoA (-0.941 to 1.113) compared with X-ray
      mammography and histopathology (mean difference -0.658, 95% LoA -3.503 to 2.187).
      When the level of agreement was assessed between clinically relevant subgroups
      additional significant differences were noted based on grade, hormonal receptor
      status, invasion, necrosis, mircocalcifications and growth pattern. CONCLUSION:
      MRI provides a more accurate estimation of DCIS size than X-ray mammography.
      MRI's superior ability was not only noted in general, but also for clinical
      relevant subdivisions such as grade and the presence or absence of necrosis.

PMID- 25604905
TI  - Angiogenin secretion from hepatoma cells activates hepatic stellate cells to
      amplify a self-sustained cycle promoting liver cancer.
AB  - Hepatocellular carcinoma (HCC) frequently develops in a pro-inflammatory and pro
      fibrogenic environment with hepatic stellate cells (HSCs) remodeling the
      extracellular matrix composition. Molecules secreted by liver tumors contributing
      to HSC activation and peritumoral stromal transformation remain to be fully
      identified. Here we show that conditioned medium from HCC cell lines, Hep3B and
      HepG2, induced primary mouse HSCs transdifferentiation, characterized by
      profibrotic properties and collagen modification, with similar results seen in
      the human HSC cell line LX2. Moreover, tumor growth was enhanced by coinjection
      of HepG2/LX2 cells in a xenograft murine model, supporting a HCC-HSC crosstalk in
      liver tumor progression. Protein microarray secretome analyses revealed
      angiogenin as the most robust and selective protein released by HCC compared to
      LX2 secreted molecules. In fact, recombinant angiogenin induced in vitro HSC
      activation requiring its nuclear translocation and rRNA transcriptional
      stimulation. Moreover, angiogenin antagonism by blocking antibodies or angiogenin
      inhibitor neomycin decreased in vitro HSC activation by conditioned media or
      recombinant angiogenin. Finally, neomycin administration reduced tumor growth of
      HepG2-LX2 cells coinjected in mice. In conclusion, angiogenin secretion by HCCs
      favors tumor development by inducing HSC activation and ECM remodeling. These
      findings indicate that targeting angiogenin signaling may be of potential
      relevance in HCC management. 

PMID- 25604908
TI  - Racking the brain: detection of cerebral edema on postmortem computed tomography
      compared with forensic autopsy.
AB  - PURPOSE: The purpose of this study was to compare postmortem computed tomography
      with forensic autopsy regarding their diagnostic reliability of differentiating
      between pre-existing cerebral edema and physiological postmortem brain swelling.
      MATERIALS AND METHODS: The study collective included a total of 109 cases
      (n=109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively
      evaluated for the following parameters (as related to the distinct age groups and
      causes of death): tonsillar herniation, the width of the outer and inner
      cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield
      Units) of the gray and white matter. The results were compared with the findings
      of subsequent autopsies as the gold standard for diagnosing cerebral edema. p
      Values <0.05 were considered statistically significant. RESULTS: Cerebellar edema
      (despite normal postmortem swelling) can be reliably assessed using postmortem
      computed tomography and is indicated by narrowed temporal horns and symmetrical
      herniation of the cerebellar tonsils (p<0.001). There was a significant
      difference (p<0.001) between intoxication (or asphyxia) and all other causes of
      death; the former causes demonstrated higher deviations of the attenuation
      between white and gray matter (>20 Hounsfield Units), and the gray to white
      matter ratio was >1.58 when leukoencephalopathy was excluded. CONCLUSIONS:
      Despite normal postmortem changes, generalized brain edema can be differentiated
      on postmortem computed tomography, and white and gray matter Hounsfield
      measurements help to determine the cause of death in cases of intoxication or
      asphyxia. Racking the brain about feasible applications for a precise and
      reliable brain diagnostic forensic radiology method has just begun.

PMID- 25604909
TI  - Accuracy of 3 T versus 1.5 T breast MRI for pre-operative assessment of extent of
      disease in newly diagnosed DCIS.
AB  - OBJECTIVES: While 3T breast magnetic resonance imaging has increased in use over
      the past decade, there is little data comparing its use for assessing ductal
      carcinoma in situ (DCIS) versus 1.5 T. We sought to compare the accuracies of
      DCIS extent of disease measures on pre-operative 3T versus 1.5 T MRI. METHODS:
      This institutional review board-approved prospective study included 20 patients
      with ductal carcinoma in situ diagnosed by core needle biopsy (CNB) who underwent
      pre-operative breast MRI at both 3T (resolution=0.5 mm*0.5 mm*1.3 mm) and 1.5 T
      (0.85 mm*0.85 mm*1.6 mm). All patients provided informed consent, and the study
      was HIPPA compliant. Lesion sizes and imaging characteristics (morphologic and
      kinetic enhancement) were recorded for the 3 T and 1.5 T examinations. Lesion
      size measures at both field strengths were correlated to final pathology, and
      imaging characteristics also were compared. RESULTS: Of the initial cohort of 20
      patients with CNB-diagnosed DCIS, 19 underwent definitive surgery. Median DCIS
      sizes of these 19 patients were 6mm (range: 0-67 mm) on 3T, 13 mm (0-60 mm) on
      1.5 T, and 6mm (0-55 mm) on surgical pathology. Size correlation between MRI and
      pathology was higher for 3T (Spearman's rho=0.66, p=0.002) than 1.5 T (rho=0.36,
      p=0.13). In 10 women in which a residual area of suspicious enhancement was
      identified on both field strengths, there was agreement of morphologic
      description (NME vs. mass) in nine, and no significant difference in dynamic
      contrast enhanced kinetics at 3T compared to 1.5 T. CONCLUSIONS: Pre-operative
      breast MRI at 3T provided higher correlation with final pathology size of DCIS
      lesions compared to 1.5 T, and may be more accurate for assessment of disease
      extent prior to definitive surgery.

PMID- 25604910
TI  - Pulmonary lymphangioleiomyomatosis: analysis of disease manifestation by region
      based quantification of lung parenchyma.
AB  - PURPOSE: Lymphangioleiomyomatosis (LAM) is characterized by proliferation of
      smooth muscle tissue that causes bronchial obstruction and secondary cystic
      destruction of lung parenchyma. The aim of this study was to evaluate the typical
      distribution of cystic defects in LAM with quantitative volumetric chest computed
      tomography (CT). MATERIALS AND METHODS: CT examinations of 20 patients with
      confirmed LAM were evaluated with region-based quantification of lung parenchyma.
      Additionally, 10 consecutive patients were identified who had recently undergone
      CT imaging of the lung at our institution, in which no pathologies of the lung
      were found, to serve as a control group. Each lung was divided into three regions
      (upper, middle and lower thirds) with identical number of slices. In addition, we
      defined a "peel" and "core" of the lung comprising the 2 cm subpleural space and
      the remaining inner lung area. Computerized detection of lung volume and relative
      emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS,
      Bremen, Germany). This software package enables the quantification of
      emphysematous lung parenchyma by calculating the pixel index, which is defined as
      the ratio of lung voxels with a density <-950HU to the total number of voxels in
      the lung. RESULTS: Cystic changes accounted for 0.1-39.1% of the total lung
      volume in patients with LAM. Disease manifestation in the central lung was
      significantly higher than in peripheral areas (peel median: 15.1%, core median:
      20.5%; p=0.001). Lower thirds of lung parenchyma showed significantly less cystic
      changes than upper and middle lung areas combined (lower third: median 13.4,
      upper and middle thirds: median 19.0, p=0.001). CONCLUSION: The distribution of
      cystic lesions in LAM is significantly more pronounced in the central lung
      compared to peripheral areas. There is a significant predominance of cystic
      changes in apical and intermediate lung zones compared to the lung bases.

PMID- 25604911
TI  - Utilization of motor imagery in upper limb rehabilitation: a systematic scoping
      review.
AB  - OBJECTIVE: To determine how motor imagery is being delivered in upper limb
      rehabilitation to guide practice and research. DATA SOURCE: MEDLINE, PubMed,
      CINAHL, EMBASE, PsychINFO databases were searched from 1987 to November 2014
      STUDY SELECTION: English, adults, any clinical population or diagnosis,
      intervention for upper limb with an outcome measure used. All types of studies
      were included. Two authors independently selected studies for review using
      consensus. DATA EXTRACTION: Seven motor imagery elements were extracted using a
      model implemented in sport research: PETTLEP model (Physical, Environment, Task,
      Timing, Learning, Emotion, and Perspective). RESULTS: The search yielded 1107
      articles with 1059 excluded leaving 48 articles for full review. A total of 38
      articles involved individuals with stroke, five articles involved individuals
      with complex regional pain syndrome, and five articles for other conditions.
      Motor imagery elements most commonly described were physical, environment, task,
      and perspective. Elements less commonly described were timing, learning, and
      emotional aspects. There were significant differences between study populations
      (e.g. stroke and complex regional pain syndrome) and within populations on how
      motor imagery was delivered. CONCLUSION: Many of the imagery elements reviewed
      are not being considered or reported on in the selected studies. How motor
      imagery is being delivered within and between populations is inconsistent, which
      may lead to difficulties in determining key elements of effectiveness.

PMID- 25604912
TI  - Effects of anodal transcranial direct current stimulation combined with virtual
      reality for improving gait in children with spastic diparetic cerebral palsy: a
      pilot, randomized, controlled, double-blind, clinical trial.
AB  - OBJECTIVE: To compare the effects of anodal vs. sham transcranial direct current
      stimulation combined with virtual reality training for improving gait in children
      with cerebral palsy. DESIGN: A pilot, randomized, controlled, double-blind,
      clinical trial. SETTING: Rehabilitation clinics. SUBJECTS: A total of 20 children
      with diparesis owing to cerebral palsy. INTERVENTIONS: The experimental group
      received anodal stimulation and the control group received sham stimulation over
      the primary motor cortex during virtual reality training. All patients underwent
      the same training programme involving a virtual reality (10 sessions).
      Evaluations were performed before and after the intervention as well as at the
      one-month follow-up and involved gait analysis, the Gross Motor Function Measure,
      the Pediatric Evaluation Disability Inventory and the determination of motor
      evoked potentials. RESULTS: The experimental group had a better performance
      regarding gait velocity (experimental group: 0.63 +/-0.17 to 0.85 +/-0.11 m/s;
      control group: 0.73 +/-0.15 to 0.61 +/-0.15 m/s), cadence (experimental group:
      97.4 +/-14.1 to 116.8 +/-8.7 steps/minute; control group: 92.6 +/-10.4 to 99.7 +/
      9.7 steps/minute), gross motor function (dimension D experimental group: 59.7 +/
      12.8 to 74.9 +/-13.8; control group: 58.9 +/-10.4 to 69.4 +/-9.3; dimension E
      experimental group: 59.0 +/-10.9 to 79.1 +/-8.5; control group: 60.3 +/-10.1 to
      67.4 +/-11.4) and independent mobility (experimental group: 34.3 +/-5.9 to 43.8
      +/-75.3; control group: 34.4 +/-8.3 to 37.7 +/-7.7). Moreover, transcranial
      direct current stimulation led to a significant increase in motor evoked
      potential (experimental group: 1.4 +/-0.7 to 2.6 +/-0.4; control group: 1.3 +/
      0.6 to 1.6 +/-0.4). CONCLUSION: These preliminary findings support the hypothesis
      that anodal transcranial direct current stimulation combined with virtual reality
      training could be a useful tool for improving gait in children with cerebral
      palsy.

PMID- 25604913
TI  - Implementation of a Very Low Calorie Diet in Patients Undergoing Urologic
      Surgery: Room for Improvement?

PMID- 25604914
TI  - Imaging Findings and Histologic Appearances of Alveolar Soft Part Sarcoma in the
      Prostate: A Case Report and Review of the Literature.

PMID- 25604915
TI  - Salvage Stereotactic Body Radiotherapy for Patients With Prostate Cancer With
      Isolated Lymph Node Metastasis: A Single-Center Experience.
AB  - OBJECTIVE: The study objective was to evaluate the efficacy of salvage
      stereotactic body radiation therapy (SBRT) as a treatment modality in patients
      with oligometastatic prostate cancer. METHODS: A total of 16 patients with 18
      isolated lymph nodes with recurrent prostate cancer were treated between 2008 and
      2013. All patients underwent [(11)C] choline-positron emission
      tomography/computed tomography before SBRT. Two patients were treated in
      different sessions for metachronous metastases. Ten patients received androgen
      deprivation therapy concomitant to SBRT (total dose range, 12-35 Gy, delivered in
      1-5 daily fractions). RESULTS: The mean and median follow-up periods were 29.35
      and 29.38 months, respectively (range, 6.3-68.8 months). Local disease control
      and a decrease in serum prostate-specific antigen were obtained in 15 of 16
      patients (94%); only 1 patient had an in-field progression. In the 6 patients
      without androgen deprivation therapy at the time of SBRT, the mean time of
      deferment of palliative androgen deprivation therapy was 23.7 months (range, 2.5
      51 months). At last follow-up, 8 patients had active prostate cancer disease;
      biochemical progression was observed after a mean time of 7.9 months from the
      completion of SBRT. One patient died of disease. Overall survival was 94%. The 2
      year biochemical relapse-free survival was 44%. Late toxicity (gastrointestinal)
      was observed in 1 patient who had a G3 toxicity. CONCLUSIONS: SBRT seems to be
      safe, effective, and minimally invasive in the eradication of limited nodal
      recurrence from oligometastatic prostate cancer. SBRT is well tolerated by
      patients with low toxicity and yielded a local control of the disease.

PMID- 25604916
TI  - GPR40 agonists for the treatment of type 2 diabetes: life after 'TAKing' a hit.
AB  - The free fatty acid receptor GPR40 has been proposed as a potential target for
      type 2 diabetes (T2D) pharmacotherapy. This idea has been validated in both
      preclinical and clinical studies, in which activation of GPR40 was shown to
      improve glycaemic control by stimulating glucose-dependent insulin secretion;
      however, the recent termination of phase III clinical trials using the GPR40
      agonist TAK-875 (fasiglifam) has raised important questions regarding the long
      term safety and viability of targeting GPR40 and, more specifically, about our
      understanding of this receptor's basic biology. In the present review, we provide
      a summary of established and novel concepts related to GPR40's pharmacobiology
      and discuss the current status and future outlook for GPR40-based drug
      development for the treatment of T2D. 

PMID- 25604917
TI  - [Cognitive deficits in unipolar major depression].
AB  - Cognitive deficits are common symptom presentations in neurology and psychiatry.
      Cognitive symptoms during major depressive episodes cause subjective distress as
      well as difficulties during therapy and psychosocial reintegration. Depression
      associated cognitive symptoms are characterized by a mood-congruent information
      processing bias as well as by cognitive performance deficits. A diagnostically
      relevant profile of neuropsychological impairments specific to depression has not
      yet been identified. Nevertheless, deficits of executive and declarative memory
      functions have repeatedly been reported. The time course of cognitive deficits
      after remission of mood is not entirely clear. Depending on the point of time of
      the reinvestigation, patients may still exhibit pronounced cognitive deficits.
      This article presents the current knowledge about cognitive symptoms in major
      depression, including the pathophysiology and treatment options. 

PMID- 25604918
TI  - Plant community change mediates the response of foliar delta(15)N to CO 2
      enrichment in mesic grasslands.
AB  - Rising atmospheric CO2 concentration may change the isotopic signature of plant N
      by altering plant and microbial processes involved in the N cycle. CO2 may
      increase leaf delta(15)N by increasing plant community productivity, C input to
      soil, and, ultimately, microbial mineralization of old, (15)N-enriched organic
      matter. We predicted that CO2 would increase aboveground productivity (ANPP; g
      biomass m(-2)) and foliar delta(15)N values of two grassland communities in
      Texas, USA: (1) a pasture dominated by a C4 exotic grass, and (2) assemblages of
      tallgrass prairie species, the latter grown on clay, sandy loam, and silty clay
      soils. Grasslands were exposed in separate experiments to a pre-industrial to
      elevated CO2 gradient for 4 years. CO2 stimulated ANPP of pasture and of prairie
      assemblages on each of the three soils, but increased leaf delta(15)N only for
      prairie plants on a silty clay. delta(15)N increased linearly as mineral
      associated soil C declined on the silty clay. Mineral-associated C declined as
      ANPP increased. Structural equation modeling indicted that CO2 increased ANPP
      partly by favoring a tallgrass (Sorghastrum nutans) over a mid-grass species
      (Bouteloua curtipendula). CO2 may have increased foliar delta(15)N on the silty
      clay by reducing fractionation during N uptake and assimilation. However, we
      interpret the soil-specific, delta(15)N-CO2 response as resulting from increased
      ANPP that stimulated mineralization from recalcitrant organic matter. By
      contrast, CO2 favored a forb species (Solanum dimidiatum) with higher delta(15)N
      than the dominant grass (Bothriochloa ischaemum) in pasture. CO2 enrichment
      changed grassland delta(15)N by shifting species relative abundances.

PMID- 25604919
TI  - Neighbouring populations, opposite dynamics: influence of body size and
      environmental variation on the demography of stream-resident brown trout (Salmo
      trutta).
AB  - In organisms such as fish, where body size is considered an important state
      variable for the study of their population dynamics, size-specific growth and
      survival rates can be influenced by local variation in both biotic and abiotic
      factors, but few studies have evaluated the complex relationships between
      environmental variability and size-dependent processes. We analysed a 6-year
      capture-recapture dataset of brown trout (Salmo trutta) collected at 3
      neighbouring but heterogeneous mountain streams in northern Spain with the aim of
      investigating the factors shaping the dynamics of local populations. The
      influence of body size and water temperature on survival and individual growth
      was assessed under a multi-state modelling framework, an extension of classical
      capture-recapture models that considers the state (i.e. body size) of the
      individual in each capture occasion and allows us to obtain state-specific
      demographic rates and link them to continuous environmental variables. Individual
      survival and growth patterns varied over space and time, and evidence of size
      dependent survival was found in all but the smallest stream. At this stream, the
      probability of reaching larger sizes was lower compared to the other wider and
      deeper streams. Water temperature variables performed better in the modelling of
      the highest-altitude population, explaining over a 99 % of the variability in
      maturation transitions and survival of large fish. The relationships between body
      size, temperature and fitness components found in this study highlight the
      utility of multi-state approaches to investigate small-scale demographic
      processes in heterogeneous environments, and to provide reliable ecological
      knowledge for management purposes.

PMID- 25604920
TI  - Biofilm formation on a TiO2 nanotube with controlled pore diameter and surface
      wettability.
AB  - Titania (TiO2) nanotube arrays (TNAs) with different pore diameters (140 - 20 nm)
      are fabricated via anodization using hydrofluoric acid (HF) containing ethylene
      glycol (EG) by changing the HF-to-EG volume ratio and the anodization voltage. To
      evaluate the effects of different pore diameters of TiO2 nanotubes on bacterial
      biofilm formation, Shewanella oneidensis (S. oneidensis) MR-1 cells and a crystal
      violet biofilm assay are used. The surface roughness and wettability of the TNA
      surfaces as a function of pore diameter, measured via the contact angle and AFM
      techniques, are correlated with the controlled biofilm formation. Biofilm
      formation increases with the decreasing nanotube pore diameter, and a 20 nm TiO2
      nanotube shows the maximum biofilm formation. The measurements revealed that 20
      nm surfaces have the least hydrophilicity with the highest surface roughness of
      ~17 nm and that they show almost a 90% increase in the effective surface area
      relative to the 140 nm TNAs, which stimulate the cells more effectively to
      produce the pili to attach to the surface for more biofilm formation. The results
      demonstrate that bacterial cell adhesion (and hence, biofilm formation) can
      effectively be controlled by tuning the roughness and wettability of TNAs via
      controlling the pore diameters of TNA surfaces. This biofilm formation as a
      function of the surface properties of TNAs can be a potential candidate for both
      medical applications and as electrodes in microbial fuel cells.

PMID- 25604921
TI  - Response of soil microbial activity and biodiversity in soils polluted with
      different concentrations of cypermethrin insecticide.
AB  - We performed a laboratory study into the effect of cypermethrin insecticide
      applied to different concentrations on biological properties in two soils [Typic
      Xerofluvent (soil A) and Xerollic Calciorthid (soil B)]. Two kg of each soil were
      polluted with cypermethrin at a rate of 60, 300, 600, and 1,200 g ha(-1) (C1, C2,
      C3, and C4 treatments). A nonpolluted soil was used as a control (C0 treatment).
      For all treatments and each experimental soil, soil dehydrogenase, urease, beta
      glucosidase, phosphatase, and arylsulphatase activities and soil microbial
      community were analysed by phospholipid fatty acids, which were measured at six
      incubation times (3, 7, 15, 30, 60, and 90 days). The behavior of the enzymatic
      activities and microbial population were dependent on the dose of insecticide
      applied to the soil. Compared with the C0 treatment, in soil A, the maximum
      inhibition of the enzymatic activities was at 15, 30, 45, and 90 days for the C1,
      C2, C3, and C4 treatments, respectively. However, in soil B, the maximum
      inhibition occurred at 7, 15, 30, and 45 days for the C1, C2, C3, and C4
      treatments, respectively. These results suggest that the cypermethrin insecticide
      caused a negative effect on soil enzymatic activities and microbial diversity.
      This negative impact was greater when a greater dose of insecticide was used;
      this impact was also greater in soil with lower organic matter content. For both
      soils, and from these respective days onward, the enzymatic activities and
      microbial populations progressively increased by the end of the experimental
      period. This is possibly due to the fact that the insecticide or its breakdown
      products and killed microbial cells, subsequently killed by the insecticide, are
      being used as a source of energy or as a carbon source for the surviving
      microorganisms for cell proliferation.

PMID- 25604922
TI  - Ammonia toxicity to the freshwater planarian Polycelis felina: contrasting
      effects of continuous versus discontinuous exposures.
AB  - Aquatic animals can be exposed to fluctuating concentrations of toxicants. In
      fact, for some toxicants (i.e., pesticides, ammonia), discontinuous exposure is
      more environmentally relevant than constant exposure. Responses of aquatic
      animals to each type of exposure may be different. However, despite the high
      ecological relevance of behaviour, there is still scarce information on the
      effects of discontinuous exposure on behaviour. Our study focused on the
      assessment of unionized ammonia toxicity on the behaviour of a freshwater
      planarian under continuous exposure (3 days of exposure and 18 days of recovery)
      versus discontinuous exposure (3 pulses of 1 day with 6 days of recovery between
      pulses = total 3 days of exposure and 18 days of recovery). Behaviour was
      assessed as locomotion activity. Bioassays with continuous and discontinuous
      exposure were performed with one control and five unionized ammonia
      concentrations (0.14-0.35 mg N-NH3/L). Unionized ammonia in continuous exposure
      caused less impact on behaviour than equivalent concentrations provided in a
      discontinuous exposure. By contrast, continuous exposures caused more impact on
      survival. The discontinuous exposure may allow detoxification during recovery
      periods, thus increasing the probability of survival in the next pulse. Under
      continuous exposure, the mortality threshold could be exceeded, and animals could
      die in greater proportion during exposure as well as the recovery period. We
      conclude that behavioural activity was a sensitive endpoint to assess the
      contrasting effects of continuous versus discontinuous exposure and that the
      response of planarians to discontinuous exposure is different to its response to
      continuous exposure.

PMID- 25604923
TI  - Effect of 10% dietary protein intake on whole body protein kinetics in type 2
      diabetic adults.
AB  - BACKGROUND & AIMS: Insulin resistance of protein metabolism occurs in obesity and
      type 2 diabetes (T2D). Hyperaminoacidemia during a simulated fed steady-state
      clamp compensates for this resistance. We tested whether decreasing protein
      intake affects the response to insulin with or without added amino acids, and if
      this response differs by sex. METHODS: Protein intake was reduced from usual
      (15%) to 10% of an isoenergetic diet energy for 11 days, in T2D obese men (n = 8)
      and women (n = 10). Whole-body leucine kinetics (1-(13)C-leucine, surrogate for
      protein) were determined postabsorptive and during a hyperinsulinemic (~600
      pmol/L), hyperglycemic (8 mmol/L), isoaminoacidemic, followed by
      hyperaminoacidemic clamp and compared to those of T2D men on a 17% protein diet.
      RESULTS: Initial negative nitrogen balance approached equilibrium by day 10 but
      remained lower than with the 17% protein diet. During the hyperinsulinemic,
      isoaminoacidemic clamp, total leucine flux was less, with both lower endogenous
      rates of appearance (catabolism) and nonoxidative rates of disposal (synthesis),
      resulting in net balance at zero. With hyperaminoacidemia, net balance increased
      to 0.39 +/- 0.09 MUmol/kgLBM?min in men, significantly less than in men on 17%
      protein (0.98 +/- 0.09, p < 0.01). There were no sex differences in clamp
      responses with 10% protein. CONCLUSIONS: After 11 days of 10% protein diet, there
      was a slight improvement in insulin sensitivity, but a blunted anabolic response
      to hyperaminoacidemia. Longer-term consequences of lesser anabolic efficiency at
      reduced protein intakes require study and may contribute to increased risk of
      sarcopenia in persons with T2D with aging.

PMID- 25604924
TI  - Keratolytics and emollients and their role in the therapy of psoriasis: a
      systematic review.
AB  - INTRODUCTION: Psoriasis is a common chronic disease with significant impairment
      in quality of life. As there is no cure, it often requires lifelong disease
      control to minimize the development of skin lesions and to relieve symptoms. The
      aim of this publication is to systematically review the role of currently used
      emollients and keratolytics in the treatment of psoriasis. METHODS: A systematic
      literature search was conducted in Medline via PubMed regarding reviews, meta
      analyses, and trials published from January 1983 to December 2013 dealing with
      topical administration of emollients and keratolytics in patients with psoriasis.
      A subsequent search in EMBASE regarding clinical trials published from 1983 to
      2013 was performed to complement the findings. RESULTS: A total of 60
      publications met the inclusion criteria for full-text evaluation. While current
      reviews, meta-analyses, and guidelines state that adjuvant therapy with
      emollients and keratolytics should be an obligatory part in the therapy of
      psoriasis to facilitate descaling and/or penetration enhancement, comprehensive
      trials on these agents are missing, with the exception of combination products
      containing salicylic acid and corticosteroids. In the mentioned trials, addition
      of salicylic acid was beneficial in inducing a more rapid onset of action as well
      as a reduction of severity parameters and the area affected. However, its use has
      substantial limitations in young children, in patients with renal/hepatic
      impairment, with widespread psoriasis, those undergoing phototherapy, or those
      concomitantly treated with calcipotriene/systemic salicylates. CONCLUSION: In
      view of these shortcomings, there is a need for well-designed studies on suitable
      keratolytic alternatives to salicylic acid offering an indisputable positive
      benefit-risk ratio.

PMID- 25604925
TI  - Molecular characterization, phylogenetic analysis and expression profiling of
      myoglobin and cytoglobin genes in response to heat stress in channel catfish
      Ictalurus punctatus.
AB  - To understand the function of myoglobin (Mb) and cytoglobin (Cygb) in channel
      catfish Ictalurus punctatus in response to heat stress, mb and cygb genes were
      identified and characterized in this study. These genes were widely expressed in
      all the tested tissues, but strong tissue preferences were observed, with the mb
      gene being expressed most highly in the heart, cygb1 most highly expressed in the
      intestine and cygb2 most highly expressed in the brain. After heat-stress
      challenge, mb and cygb genes were up-regulated in almost all tested tissues. In
      general, such up-regulation was more dramatic in the tolerant group than in the
      intolerant group, suggesting that higher expression of mb and cygb genes
      contributed to greater tolerance of I. punctatus to heat stress.

PMID- 25604926
TI  - Two novel reassortants of avian influenza A (H5N6) virus in China.
AB  - Eight avian influenza A (H5N6) viruses were isolated from live poultry markets
      (LPMs) in Sichuan and Jiangxi Provinces in China in 2014, including those close
      to the county where the human H5N6 infection occurred. Genetic and phylogenetic
      analyses revealed that these H5N6 viruses were novel reassortants between H5N1
      clade 2.3.4 and H6N6 viruses, and had evolved into two distinct lineages (Sichuan
      and Jiangxi). Moreover, the human H5N6 virus was closely related to the avian
      source viruses of Sichuan lineage. Notably, H5N6 viruses contained a T160A
      substitution in the haemagglutinin protein and an 11 aa deletion in the
      neuraminidase stalk, which may aid in enhancing viral affinity for human-like
      receptors and virulence in mammals. As the H5N1 virus infects humans through
      direct contact, infection with the novel H5N6 virus raised significant concerns
      that the H5 subtype was a likely candidate for a pandemic. Therefore, extensive
      and long-term surveillance of avian influenza viruses in LPMs is essential.

PMID- 25604927
TI  - Identification of a functional motif in the AqRV NS26 protein required for
      enhancing the fusogenic activity of FAST protein NS16.
AB  - Aquareoviruses AqRVs have a close relationship with orthoreoviruses. However,
      they contain an additional genome segment, S11, which encodes nonstructural
      protein NS26. We previously showed that NS26 can enhance the fusogenic activity
      of the fusion-associated small transmembrane FAST protein NS16 from AqRV. In this
      study, a TLPK motif in NS26 was identified as being important for the
      enhancement. When the TLPK motif was deleted from NS26, the enhanced efficiency
      of the NS16-mediated cellcell fusion was significantly impaired. Further
      mutational analysis showed that the lysine K residue in the TLPK motif was
      critical for the enhancement. Additionally, deletion of the TLPK motif prevented
      NS26 from interacting with lysosomes. These findings suggested that the TLPK
      motif is important for NS26 to enhance the fusogenic activity of NS16, and NS26
      may utilize the lysosome to benefit the fusion process.

PMID- 25604928
TI  - Regulated protonation of polyaspartamide derivatives bearing repeated
      aminoethylene side chains for efficient intracellular siRNA delivery with minimal
      cytotoxicity.
AB  - The effects of the repeated number (RN) of aminoethylene (AE) units in
      polyaspartamide side chains were investigated for polyion complex (PIC)-based
      siRNA delivery. Reduction of the apparent RN from 3 to 2 by thiourea introduction
      increased a protonatable amine fraction in AE units at endosomal pH, leading to
      the efficient endosomal escape of siRNA-loaded PICs. 

PMID- 25604929
TI  - Effects of persistent atrial fibrillation on serum galectin-3 levels.
AB  - Galectin-3 is known to play an important role in a number of fibrotic conditions,
      including cardiac fibrosis. Many studies have focused on the association between
      galectin-3 levels and cardiac fibrosis in heart failure. However, the role of
      galectin-3 in the pathogenesis of atrial fibrillation (AF) has not been evaluated
      thoroughly yet. The aim of this study was to determine whether serum galectin-3
      levels were elevated in patients with AF and preserved left ventricular function.
      Seventy-six patients with paroxysmal or persistent AF and preserved left
      ventricular systolic function and 75 age- and gender-matched control subjects
      were enrolled in this observational study. Galectin-3 levels were measured by
      enzyme-linked immunosorbent assay. Serum galectin-3 (median 0.6 ng/ml
      [interquartile range 0.2 to 1.4] vs 0.5 ng/ml [interquartile range 0.1 to 0.7], p
      <0.001) and left atrial volume index (LAVI) (mean 29.5 +/- 3.5 vs 26.5 +/- 2.5
      ml/m(2), p <0.001) were significantly greater in patients with AF compared with
      the control group. Serum galectin-3 levels were also significantly higher in
      patients with persistent AF than those with paroxysmal AF (median 0.8 ng/ml
      [interquartile range 0.4 to 1.4] vs 0.5 ng/ml [interquartile range 0.2 to 0.9], p
      <0.001). Multivariate regression analysis demonstrated that serum galectin-3
      (odds ratio 87.53, 95% confidence interval 6.06 to 1,265.03, p = 0.001) and LAVI
      (odds ratio 1.38, 95% confidence interval 1.19 to 1.60, p <0.001) were
      independent predictors of AF. Only LAVI was independently correlated with serum
      galectin-3 levels in patients with AF in linear regression analysis. In
      conclusion, serum galectin-3 is significantly elevated and is also significantly
      correlated with LAVI in patients with AF with preserved left ventricular
      function. 

PMID- 25604930
TI  - Additive prognostic value of coronary artery calcium score over coronary computed
      tomographic angiography stenosis assessment in symptomatic patients without known
      coronary artery disease.
AB  - The objective of this study was to examine the additive prognostic performance of
      coronary artery calcium score (CACS) over coronary computed tomography
      angiography (CCTA) stenosis assessment in symptomatic patients suspected for
      coronary artery disease (CAD) undergoing CCTA. A total of 805 symptomatic
      patients without known history of CAD who underwent coronary evaluation by
      multidetector cardiac CT were analyzed. Mean age of the cohort was 58 +/- 13
      years. A total of 44% (354 of 805) of the patients had a 0 CACS, 27% (215 of 805)
      had CACS 1 to 100, 14% (111 of 805) had CACS 101 to 400, and 15% (125 of 805) had
      CACS >400. CCTA showed normal coronary arteries in 43% (349 of 805) of patients,
      <=50% stenosis in 42% (333 of 805), and >50% stenosis in 15% (123 of 805).
      Patients were followed for 2.3 +/- 0.9 years. Major adverse cardiac event (MACE)
      was defined as cardiac death, nonfatal myocardial infarction, and late coronary
      revascularization. Overall incidence of MACE was 1.4% per year. Both CACS and
      CCTA stenosis were independently associated with increased MACE (p <0.05 for
      both). Addition of CACS into the model with clinical risk factors and CCTA
      stenosis significantly improved predictive performance for MACE from the model
      with clinical risk factors and CCTA stenosis only (global chi-square score 108 vs
      70; p = 0.019). In conclusion; in symptomatic patients without known CAD, both
      CACS and CCTA stenosis were independently associated with increased cardiac
      events, and performing non-contrast-enhanced CACS evaluation in addition to
      contrast-enhanced CCTA improved predictive ability for future cardiac events
      compared to CCTA stenosis assessment alone.

PMID- 25604931
TI  - Effect of a shortened-duration Eptifibatide infusion (75 mg) as adjunctive
      therapy for percutaneous coronary intervention on in-hospital cardiovascular
      outcomes and bleeding.
AB  - A retrospective cohort analysis was conducted on patients who underwent
      percutaneous coronary intervention (PCI) before and after a practice change which
      reduced the infusion duration of eptifibatide from 18 hours to the time required
      for completion of a single vial of 75 mg initiated during PCI. Primary end points
      were inhospital cardiovascular events, target vessel revascularization, and major
      or minor bleeding. The secondary end point was drug cost. A total of 1,647
      patients received the standard-duration infusion (18 hours), and 1,237 received
      the short-duration infusion. The median infusion times were 18.1 hours
      (interquartile range 17.7 to 18.7) and 6.6 hours (interquartile range 5.6 to
      11.3) in the standard- and short-duration groups, respectively. No differences
      were found for the rate of inhospital cardiovascular events (2.0% vs 1.9%,
      respectively; p = 0.78) or inhospital revascularization (0.2% vs 0.3%,
      respectively; p = 0.68). Also, no statistically significant difference was
      observed in major bleeding (standard 4.3% vs short 4.4%; p = 0.94) or minor
      bleeding (standard 3.3% vs short 2.3%; p = 0.09). In conclusion, using a
      shortened infusion reduced eptifibatide use by an average of 1.6 vials at cost
      savings of $823 per patient and resulted in no difference in inhospital
      cardiovascular events, revascularization, or bleeding.

PMID- 25604932
TI  - Acute schistosomiasis: a risk underestimated by travelers and a diagnosis
      frequently missed by general practitioners-a cluster analysis of 42 travelers.
AB  - BACKGROUND: In 2011, a patient was admitted to our hospital with acute
      schistosomiasis after having returned from Madagascar and having bathed at the
      Lily waterfalls. On the basis of this patient's indication, infection was
      suspected in 41 other subjects. This study investigated (1) the knowledge of the
      travelers about the risks of schistosomiasis and their related behavior to
      evaluate the appropriateness of prevention messages and (2) the diagnostic workup
      of symptomatic travelers by general practitioners to evaluate medical care of
      travelers with a history of freshwater exposure in tropical areas. METHODS: A
      questionnaire was sent to the 42 travelers with potential exposure to
      schistosomiasis. It focused on pre-travel knowledge of the disease, bathing
      conditions, clinical presentation, first suspected diagnosis, and treatment.
      RESULTS: Of the 42 questionnaires, 40 (95%) were returned, among which 37
      travelers (92%) reported an exposure to freshwater, and 18 (45%) were aware of
      the risk of schistosomiasis. Among these latter subjects, 16 (89%) still reported
      an exposure to freshwater. Serology was positive in 28 (78%) of 36 exposed
      subjects at least 3 months after exposure. Of the 28 infected travelers, 23 (82%)
      exhibited symptoms and 16 (70%) consulted their general practitioner before the
      information about the outbreak had spread, but none of these patients had a
      serology for schistosomiasis done during the first consultation. CONCLUSIONS: The
      usual prevention message of avoiding freshwater contact when traveling in
      tropical regions had no impact on the behavior of these travelers, who still went
      swimming at the Lily waterfalls. This prevention message should, therefore, be
      either modified or abandoned. The clinical presentation of acute schistosomiasis
      is often misleading. General practitioners should at least request an eosinophil
      count, when confronted with a returning traveler with fever. If eosinophilia is
      detected, it should prompt the search for a parasitic disease.

PMID- 25604933
TI  - Health literacy in patients referred for transplant: do patients have the
      capacity to understand?
AB  - Adequate levels of health literacy are needed for transplant recipients to be
      able to understand and comply with medical recommendations. However, little is
      known about health literacy among transplant candidates. Therefore, the purpose
      of this study was to examine the levels of health literacy and cognitive
      functioning among patients being evaluated for various types of transplantation.
      There were 398 patients who completed a required psychological evaluation prior
      to being listed for transplant. This included a screen for cognitive impairment
      and limited reading and math ability. The prevalence of limited reading ability
      was 27.5%, limited math ability was 42.8%, and 30.7% had probable cognitive
      impairment. Rates of limited reading and math ability and cognitive impairment
      varied for each type of end-stage disease. Limited reading ability was related to
      poorer cognitive functioning. Those with a higher likelihood of limited reading
      ability included blacks and males. Those more likely to have cognitive impairment
      included blacks and patients who are older. Results from this study suggest that
      patients should be regularly screened for health literacy and cognitive
      impairment. Once patients with difficulties are identified, recommendations can
      be provided to these patients at a level that they are able to understand. 

PMID- 25604934
TI  - Health and Utilities in Patients With Gout Under the Care of a Rheumatologist.
AB  - OBJECTIVE: To compare limitations in health between Dutch patients with gout and
      the general population and to determine factors influencing societal and patient
      values for health as assessed with different utility approaches. METHODS: A cross
      sectional study was done among 110 patients with gout under the care of a
      rheumatologist, with patients completing the EuroQol 5-domain instrument (EQ-5D),
      the EQ-5D visual analog scale (EQ-5D VAS), and the Short Form 6-dimensions health
      survey (SF-6D). Scores on EQ-5D domains were compared with age- and sex-matched
      general population data. Agreement between utility measures was assessed using
      the intraclass correlation coefficient (ICC). Mixture modeling was used to assess
      factors associated with the different approaches to assess utility. RESULTS:
      Compared to the general population, gout patients reported more limitations in
      mobility (66% versus 12%), self-care (24% versus 8%), daily activities (49%
      versus 24%), and pain (76% versus 45%), but equal anxiety/depressive symptoms
      (18% versus 19%). For patients with gout, utilities were reduced: the mean,
      median, and interquartile range, respectively, were 0.74, 0.81, and 0.69-0.84 for
      EQ-5D, 0.69, 0.67, and 0.59-0.81 for SF-6D, and 66, 70, and 57-77 for EQ-5D VAS.
      ICC agreement between each pair of utilities was only moderate (0.52-0.59). Only
      minor differences were seen in the type of variables associated with each utility
      approach, with worse Health Assessment Questionnaire scores, cardiovascular
      disease (CVD), gout concern, and gout pain consistently associated with lower
      utility. The strength of contribution of these variables, however, differed among
      the 3 approaches. CONCLUSION: Patients with gout experience substantially
      impaired health compared to the general population. Although absolute values of
      utility varied between instruments and perspectives, functional disability, CVD,
      and higher gout impact contributed to utility independently of which instrument
      was used.

PMID- 25604935
TI  - Do relationships between environmental attributes and recreational walking vary
      according to area-level socioeconomic status?
AB  - Residents of areas with lower socioeconomic status (SES) are known to be less
      physically active during leisure time. Neighborhood walkability has been shown to
      be related to recreational walking equally in low and high SES areas. This cross
      sectional study tested whether associations of specific environmental attributes,
      measured objectively and subjectively, with walking for recreation were moderated
      by area-level SES. The data of the North West Adelaide Health Study collected in
      2007 (n = 1500, mean age 57) were used. Self-reported walking frequency was the
      outcome of the study. Environmental exposure measures included objectively
      measured walkability components (residential density, intersection density, land
      use mix, and net retail area ratio) and perceived attributes (access to
      destinations, neighborhood esthetics, walking infrastructure, traffic/barriers,
      and crime safety). Participants' suburbs were categorized into low and high SES
      areas using an indicator of socioeconomic disadvantage. Low SES areas had lower
      scores in residential density, neighborhood esthetics, walking infrastructure,
      traffic/barriers, and crime safety. Recreational walking was associated with
      residential density, access to destinations, esthetics, traffic/barriers, and
      crime safety. Effect modification was observed for two attributes (out of nine):
      residential density was associated with walking only in low SES areas, while
      walking infrastructure was associated with walking only in high SES areas. The
      associations of neighborhood environmental attributes with recreational walking
      were largely consistent across SES groups. However, low SES areas were
      disadvantaged in most perceived environmental attributes related to recreational
      walking. Improving such attributes in low SES neighborhoods may help close
      socioeconomic disparities in leisure time physical activity.

PMID- 25604937
TI  - Electronic structures and electronic spectra of all-boron fullerene B40.
AB  - This study is motivated by the recent discovery of the first all-boron fullerene
      analogue, a B40 cluster with D(2d) point-group symmetry, dubbed borospherene
      (Nat. Chem., 2014, 6, 727). Insight into the electronic structures and spectral
      properties of B40 is timely and important to understand the borospherene and the
      transition from open-ended plate or ribbon-like structures to a hollow-cage
      structure at B40. Optimized geometries of borospherene B40 for both the ground
      state and the first excited state allow us to compute spectral properties
      including UV-vis absorption, infrared (IR) and Raman spectra. Highly resolved
      absorption and emission spectra are obtained, for the first time, for the
      fullerene at the time-dependent density-functional theory (TD-DFT) level within
      the Franck-Condon approximation and including the Herzberg-Teller effect.
      Assigned vibrational modes in absorption and emission spectra are readily
      compared with future spectroscopy measurements to distinguish the hollow-cage
      structure of D(2d)-B40 from other quasi-planar boron structures.

PMID- 25604936
TI  - Integral membrane protein structure determination using pseudocontact shifts.
AB  - Obtaining enough experimental restraints can be a limiting factor in the NMR
      structure determination of larger proteins. This is particularly the case for
      large assemblies such as membrane proteins that have been solubilized in a
      membrane-mimicking environment. Whilst in such cases extensive deuteration
      strategies are regularly utilised with the aim to improve the spectral quality,
      these schemes often limit the number of NOEs obtainable, making complementary
      strategies highly beneficial for successful structure elucidation. Recently,
      lanthanide-induced pseudocontact shifts (PCSs) have been established as a
      structural tool for globular proteins. Here, we demonstrate that a PCS-based
      approach can be successfully applied for the structure determination of integral
      membrane proteins. Using the 7TM alpha-helical microbial receptor pSRII, we show
      that PCS-derived restraints from lanthanide binding tags attached to four
      different positions of the protein facilitate the backbone structure
      determination when combined with a limited set of NOEs. In contrast, the same set
      of NOEs fails to determine the correct 3D fold. The latter situation is
      frequently encountered in polytopical alpha-helical membrane proteins and a PCS
      approach is thus suitable even for this particularly challenging class of
      membrane proteins. The ease of measuring PCSs makes this an attractive route for
      structure determination of large membrane proteins in general. 

PMID- 25604938
TI  - Atmospheric mercury in the Canadian Arctic. Part II: insight from modeling.
AB  - A review of mercury in the Canadian Arctic with a focus on field measurements is
      presented in part I (see Steffen et al., this issue). Here we provide insights
      into the dynamics of mercury in the Canadian Arctic from new and published
      mercury modeling studies using Environment Canada's mercury model. The model
      simulations presented in this study use global anthropogenic emissions of mercury
      for the period 1995-2005. The most recent modeling estimate of the net gain of
      mercury from the atmosphere to the Arctic Ocean is 75 Mg year(-1) and the net
      gain to the terrestrial ecosystems north of 66.5 degrees  is 42 Mg year(-1).
      Model based annual export of riverine mercury from North American, Russian and
      all Arctic watersheds to the Arctic Ocean are in the range of 2.8-5.6, 12.7-25.4
      and 15.5-31.0 Mg year(-1), respectively. Analysis of long-range transport events
      of Hg at Alert and Little Fox Lake monitoring sites indicates that Asia
      contributes the most ambient Hg to the Canadian Arctic followed by contributions
      from North America, Russia, and Europe. The largest anthropogenic Hg deposition
      to the Canadian Arctic is from East Asia followed by Europe (and Russia), North
      America, and South Asia. An examination of temporal trends of Hg using the model
      suggests that changes in meteorology and changes in anthropogenic emissions
      equally contribute to the decrease in surface air elemental mercury
      concentrations in the Canadian Arctic with an overall decline of ~12% from 1990
      to 2005. A slow increase in net deposition of Hg is found in the Canadian Arctic
      in response to changes in meteorology. Changes in snowpack and sea-ice
      characteristics and increase in precipitation in the Arctic related with climate
      change are found to be primary causes for the meteorology-related changes in air
      concentrations and deposition of Hg in the region. The model estimates that under
      the emissions reduction scenario of worldwide implementation of the best emission
      control technologies by 2020, mercury deposition could potentially be reduced by
      18-20% in the Canadian Arctic.

PMID- 25604939
TI  - Influence of beer marinades on the reduction of carcinogenic heterocyclic
      aromatic amines in charcoal-grilled pork meat.
AB  - The effect of beer marinades on the formation of heterocyclic aromatic amines
      (HAs) was examined in charcoal-grilled pork. Pilsner, non-alcoholic pilsner and
      black beers (coded respectively as PB, P0B and BB) were assayed and unmarinated
      samples cooked under similar conditions provided reference HAs levels. Two
      thermic (PhIP and 4,8-DiMeIQx) and three pyrolytic HAs (Trp-P-1, AalphaC,
      MeAalphaC) were quantified in unmarinated meat samples. Marinating meat in beer
      resulted in a significant decrease of PhIP, Trp-P-1 and AalphaC (p < 0.05). 4,8
      DiMeIQx formation was inhibited only by BB marinade. No significant effect was
      observed on MeAalphaC formation. All beers reduced total HA formation in charcoal
      grilled pork, black beer being the most efficient with a level of 90% inhibition.
      A strong positive correlation was observed between the inhibitory effect of beer
      on total HA formation and their antioxidant activity. Beer marinades mitigate the
      impact of consumption of well-done grilled pork meat reducing the formation of
      cooking carcinogens. 

PMID- 25604940
TI  - Effects of polluted air on cardiovascular and hematological parameters after
      progressive maximal aerobic exercise.
AB  - PURPOSE: Exercising or doing physical activity in polluted air could expose a
      person to the adverse health effects of air pollution. This study aimed to
      compare the cardiovascular and hematologic indices following an incremental
      exercise test (shuttle run) under clean versus polluted air conditions. METHODS:
      Nineteen male athletes aged 21-27 years were assigned to either a trained
      athletes group (TA, n = 10) or a complete training cessation/detrained athletes
      group (DA, n = 9) at least 3-4 months after their competitive season. All
      participants performed the multi-stage shuttle run test on two separate days in
      either polluted air (37.4 carbon monoxide part per million) or clean air (2.5
      carbon monoxide part per million) condition. RESULTS: When compared to the clean
      air environment, progressive incremental exercise in polluted air condition
      significantly (p < .05) decreased maximal oxygen uptake (VO2max), red blood cell
      count, and hematocrit for both TA and DA groups. Meanwhile, the participants'
      mean corpuscular hemoglobin, mean red blood cell volume, white blood cells, and
      platelets in these two groups increased significantly (p < .05) when they were
      exercised in the polluted air ambiance. Maximal heart rate and heart rate
      recovery showed significant (p = .04) increases only in the DA group. However,
      hemoglobin concentration remained unchanged in both groups. CONCLUSION: Acute
      exposure to high concentrations of pollutants during exercise resulted in decline
      in cardiovascular functions and hematological parameters in healthy athletes.

PMID- 25604941
TI  - Dried bonito dashi: taste qualities evaluated using conditioned taste aversion
      methods in wild-type and T1R1 knockout mice.
AB  - The primary taste of dried bonito dashi is thought to be umami, elicited by
      inosine 5'-monphosphate (IMP) and L-amino acids. The present study compared the
      taste qualities of 25% dashi with 5 basic tastes and amino acids using
      conditioned taste aversion methods. Although wild-type C57BL/6J mice with
      compromised olfactory systems generalized an aversion of dashi to all 5 basic
      tastes, generalization was greater to sucrose (sweet), citric acid (sour), and
      quinine (bitter) than to NaCl (salty) or monosodium L-glutamate (umami) with
      amiloride. At neutral pH (6.5-6.9), the aversion generalized to l-histidine, L
      alanine, L-proline, glycine, L-aspartic acid, L-serine, and monosodium L
      glutamate, all mixed with IMP. Lowering pH of the test solutions to 5.7-5.8
      (matching dashi) with HCl decreased generalization to some amino acids. However,
      adding lactic acid to test solutions with the same pH increased generalization to
      5'-inosine monophosphate, L-leucine, L-phenylalanine, L-valine, L-arginine, and
      taurine but eliminated generalization to L-histidine. T1R1 knockout mice readily
      learned the aversion to dashi and generalized the aversion to sucrose, citric
      acid, and quinine but not to NaCl, glutamate, or any amino acid. These results
      suggest that dashi elicits a complex taste in mice that is more than umami, and
      deleting T1R1 receptor altered but did not eliminate their ability to taste
      dashi. In addition, lactic acid may alter or modulate taste transduction or cell
      to-cell signaling.

PMID- 25604946
TI  - Horizontal gene transfer from a flowering plant to the insular pine Pinus
      canariensis (Chr. Sm. Ex DC in Buch).
AB  - Horizontal gene transfer (HGT) is viewed as very common in the plant
      mitochondrial (mt) genome, but, to date, only one case of HGT has been found in
      gymnosperms. Here we report a new case of HGT, in which a mt nad5-1 fragment was
      transferred from an angiosperm to Pinus canariensis. Quantitative assay and
      sequence analyses showed that the foreign nad5-1 is located in the mt genome of
      P. canariensis and is nonfunctional. An extensive survey in the genus Pinus
      revealed that the angiosperm-derived nad5-1 is restricted to P. canariensis and
      present across the species' range. Molecular dating based on chloroplast DNA
      suggested that the HGT event occurred in the late Miocene after P. canariensis
      split from its closest relatives, and that the foreign copy became fixed in P.
      canariensis owing to drift during its colonization of the Canary Islands. The
      mechanism of this HGT is unclear but it was probably achieved through either
      direct cell-cell contact or external vectors. Our discovery provides evidence for
      an important role of HGT in plant mt genome evolution. 

PMID- 25604947
TI  - A strong response to selection on mass-independent maximal metabolic rate without
      a correlated response in basal metabolic rate.
AB  - Metabolic rates are correlated with many aspects of ecology, but how selection on
      different aspects of metabolic rates affects their mutual evolution is poorly
      understood. Using laboratory mice, we artificially selected for high maximal mass
      independent metabolic rate (MMR) without direct selection on mass-independent
      basal metabolic rate (BMR). Then we tested for responses to selection in MMR and
      correlated responses to selection in BMR. In other lines, we antagonistically
      selected for mice with a combination of high mass-independent MMR and low mass
      independent BMR. All selection protocols and data analyses included body mass as
      a covariate, so effects of selection on the metabolic rates are mass adjusted
      (that is, independent of effects of body mass). The selection lasted eight
      generations. Compared with controls, MMR was significantly higher (11.2%) in
      lines selected for increased MMR, and BMR was slightly, but not significantly,
      higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in
      antagonistically selected lines, and BMR was slightly, but not significantly,
      lower (4.2%). Analysis of breeding values revealed no positive genetic trend for
      elevated BMR in high-MMR lines. A weak positive genetic correlation was detected
      between MMR and BMR. That weak positive genetic correlation supports the aerobic
      capacity model for the evolution of endothermy in the sense that it fails to
      falsify a key model assumption. Overall, the results suggest that at least in
      these mice there is significant capacity for independent evolution of metabolic
      traits. Whether that is true in the ancestral animals that evolved endothermy
      remains an important but unanswered question. 

PMID- 25604948
TI  - Bias in the heritability of preference and its potential impact on the evolution
      of mate choice.
AB  - The evolution of mate choice is a function of the heritability of preference.
      Estimation in the laboratory is typically made by presenting a female with a
      limited number of males. We show that such an approach produces a downwardly
      biased estimate, which we term the heritability of choice. When preference is
      treated as a threshold trait then less biased estimates are obtained particularly
      for preferences based on the relative value of the preferred trait. Because
      females in the wild typically survey on average less than five males we argue
      that the heritability of choice may be more meaningful than the heritability of
      preference. The restricted number of males surveyed can lead to a reduction in
      the phenotypic variance of the preferred trait in the group of males selected by
      the females if the phenotypic variance in preference is equal to or less than the
      phenotypic variance in the referred trait. If the phenotypic variance in
      preference exceeds that of the preferred trait then the opposite occurs. A second
      effect of the restricted number of males sampled is that females are likely to
      mate initially with males that are not the most preferred. The failure to find
      the most preferred male may account for the common observation of multiple
      matings and extra-pair copulations. We suggest that current explanations for
      polyandry need to take this failure into account. 

PMID- 25604949
TI  - Cellular and nephrotoxicity of selenium species.
AB  - PROJECT: Beside its useful functions at very low concentrations, selenium
      including supplementary Se sources pose a potential toxicological risk. The
      toxicity of selenium species was tested in HaCaT cell culture and related
      nephrotoxicity in mice. PROCEDURE: The apoptotic shrinkage and necrotic expansion
      of cells were measured by time-lapse image microscopy. Acute nephrotoxicity was
      estimated upon administration of various selenium species to mice for two weeks.
      To confirm or to refute the accumulation of Se in the kidney and its potential
      chronic effect, Se concentration in kidney tissue and histopathlology were
      tested. RESULTS: The comparison of selenium species showed that organic
      lactomicroSe did not affect cell growth at 5ppm, but inorganic nanoSe severely
      hampered it at lower concentration (1ppm). The in vivo Se treatment (0.5, 5,
      50ppm, corresponding to 4, 40 and 400MUg/kg) was misleading as it did neither
      affect the outward appearance nor the weight of the kidney. Se accumulation was
      observed after selenate, selenite, SelPlex, selenite and nanoSe administration,
      while lactomicroSe caused no traceable accumulation. In vivo, ex vivo and in
      vitro experiments reflected this order of selenium toxicity:
      selenate>selenite>SelPlex=nanoSe>lactomicroSe. CONCLUSION: Within the tested
      species lactomicroSe was the only non-nephrotoxic selenium source recommended for
      nutritional Se supplementation.

PMID- 25604950
TI  - Response of adherent cells to mechanical perturbations of the surrounding matrix.
AB  - We present a generic and unified theory to explain how cells respond to
      perturbations of their mechanical environment such as the presence of neighboring
      cells, slowly applied stretch, or gradients of matrix rigidity. Motivated by
      experiments, we calculate the local balance of forces that give rise to a
      tendency for the cell to locally move or reorient, with a focus on the
      contribution of feedback and homeostasis to cell contractility (manifested by a
      fixed displacement, strain or stress) that acts on the adhesions at the cell
      boundary. These forces can be either reinforced or diminished by elastic stresses
      due to mechanical perturbations of the matrix. Our model predicts these changes
      and how their balance with local protrusive forces that act on the cell's leading
      edge either increase or decrease the tendency of the cell to locally move (toward
      neighboring cells or rigidity gradients) or reorient (in the direction of slowly
      applied stretch or rigidity gradients). 

PMID- 25604951
TI  - Isolation, structure elucidation and enzyme inhibition studies of a new hydroxy
      ester and other compounds from Berberis jaeschkeana Schneid stem.
AB  - Bioassay-guided isolation and fractionation of Berberis jaeschkeana Schneid var.
      jaeschkeana stem resulted in the isolation and characterisation of a new long
      chain hydroxy ester named as berberinol (1) along with six known compounds (2-7).
      All the structures were established from 1D and 2D spectroscopic data. Crude
      extract, sub-fractions and all the isolated compounds were evaluated for their
      anti-fungal and urease enzyme inhibition properties. All of the sub-fractions and
      compounds showed good anti-fungal and urease enzyme inhibition properties.
      Minimum inhibitory concentrations (MICs) were calculated for all active samples
      in case of urease enzyme inhibition. MICs values were found to be in the range of
      39.03-49.78 MUg/mL for urease enzyme inhibition.

PMID- 25604952
TI  - Purification and characterization of a thermostable hypothetical xylanase from
      Aspergillus oryzae HML366.
AB  - In the current study, fermentation broth of Aspergillus oryzae HML366 in sugar
      cane bagasse was subjected to ultrafiltration and ion exchange chromatography,
      and two xylanases, XynH1 and XynH2, were purified. Time-of-flight mass
      spectrometry coupled with SDS-PAGE analysis revealed that XynH1 is identical to
      the hypothetical A. oryzae RIB40 protein XP_001826985.1, with a molecular weight
      of 33.671 kDa. Likewise, XynH2 was identified as xylanase XynF1 with a molecular
      weight of 35.402 kDa. Sequence analysis indicated that XynH1 belongs to glycosyl
      hydrolases family 10. The specific activity of XynH1 was measured at 476.9 U/mg.
      Optimal xylanase activity was observed at pH 6.0, and enzyme remained active
      within pH 4.0-10.0 and at a temperature below 70  degrees C. Mg(2+), Mn(2+),
      Ca(2+), and K(+) enhanced the XynH1 xylanase activity to 146, 122, 114, and 108%,
      respectively. XynH1 hydrolyzed Birchwood xylan and Larchwood xylan effectively.
      The K m and V max of XynH1 values determined were 1.16 mM and 336 MUmol/min/mg
      with Birchwood xylan as the substrate. A. oryzae HML366 xylanase XynH1 showed
      superior heat and pH tolerance, therefore may have significant applications in
      paper and biofuel industries. These studies constitute the first investigation of
      the xylanase activities of the hypothetical protein XP_001826985.1 form A.
      oryzae.

PMID- 25604953
TI  - Cellulosic ethanol fermentation using Saccharomyces cerevisiae seeds cultured by
      pretreated corn stover material.
AB  - Utilization of lignocellulose materials to replace the pure glucose for
      preparation of the fermenting yeast seeds could reduce the cost of ethanol
      fermentation, because a large quantity of glucose is saved in the large-scale
      seed fermentor series. In this study, Saccharomyces cerevisiae DQ1 was cultured
      using the freshly pretreated corn stover material as the carbon source, and then
      the culture broth was used as the inoculation seeds after a series of seed
      transfer and inoculated into the ethanol production fermentor. The results show
      that the yeast cell growth and ethanol fermentation performance have essentially
      no difference when the yeast seeds were cultured by glucose, the corn stover
      hydrolysate liquid, and the pretreated corn stover solids as carbon sources,
      respectively. Approximately 22% of the yeast cell culture cost was saved, and the
      process flow sheet in industrial scale plants was simplified by using the
      pretreated corn stover for seed culture. The results provided a practical method
      for materials and operational cost reduction for cellulosic ethanol production.

PMID- 25604954
TI  - Effects of redox mediators on anaerobic degradation of phenol by Shewanella sp.
      XB.
AB  - Up to now, no information is available on the role of redox mediators in
      anaerobic degradation of phenol without exogenous electron acceptors. The effects
      of mediators on anaerobic biodegradation of phenol by Shewanella sp. XB were
      investigated for the first time in this study. The results showed that the
      removal efficiencies of phenol were enhanced by 2.87-, 3.31-, and 2.89-fold under
      fermentation conditions in the presence of 0.20 mM anthraquinone-2-sulfonate
      (AQS), 0.05 mM anthraquinone-2,6-disulfonate (AQDS), and 0.05 mM riboflavin,
      respectively, in 3-day incubation. Further analysis found that phenol was
      fermented via volatile fatty acids (VFAs) as intermediates, particularly acetate,
      and further converted to CH4. Under denitrification conditions, phenol removal
      efficiencies were enhanced by 3.92-, 4.58-, and 3.57-fold when AQS, AQDS, and
      riboflavin, respectively, were added into reaction systems. During this process,
      phenol was preferentially degraded to CO2 and H2O rather than CH4. These results
      indicate that the three mediators not only increased significantly phenol
      biodegradation rates under fermentation conditions, but also considerably
      accelerated nitrate bioreduction-coupled phenol degradation. These findings are
      beneficial to develop efficient strategies of phenol biodegradation and to better
      understand phenol fate in natural environments. 

PMID- 25604955
TI  - Health, homeostasis, and the situation-specificity of normality.
AB  - Christopher Boorse's Biostatistical Theory of Health has been the main contender
      among naturalistic accounts of health for the last 40 years. Yet, a recent
      criticism of this theory, presented by Elselijn Kingma, identifies a dilemma
      resulting from the BST's conceptual linking of health and statistical typicality.
      Kingma argues that the BST either cannot accommodate the situation-specificity of
      many normal functions (e.g., digestion) or cannot account for many situation
      specific diseases (e.g., mountain sickness). In this article, we expand upon with
      Daniel Hausman's response to Kingma's dilemma. We propose that recalling Boorse's
      specification that health is an intrinsic property of its bearers and explicating
      this intrinsic property in relation to the concept of homeostasis can illuminate
      how proponents of naturalistic accounts of health should deal with the situation
      specificity of normal functions. We argue that beyond what Boorse and Hausman
      have delineated, the situation-specificity of normal function cannot be fully
      captured in a simple dichotomy between normal and abnormal environment or between
      relevant and irrelevant situations. By bringing homeostasis to the fore of the
      analysis of health, we set out a richer picture of what the various situations
      that affect living organisms' functional performance can be. Accordingly, we
      provide a broader classification of these various situations which, we contend,
      better accounts for the main intuitions that philosophers of medicine have sought
      to accommodate than previous naturalistic theories of health.

PMID- 25604956
TI  - Assessing assumptions of a combined structure-function index.
AB  - PURPOSE: Medeiros et al. developed a combined structure-function index for
      glaucoma by combining two ganglion cell models developed by Harwerth et al. The
      current study assessed assumptions of the Medeiros combined structure-function
      index by evaluating whether the two Harwerth models gave similar distributions of
      ganglion cells in an independent dataset. METHODS: The Harwerth models were
      applied to our previously published data for retinal nerve fibre layer (RNFL)
      thickness (Stratus OCT 3.4) and visual field sensitivities (24-2 SITA Standard)
      from one eye each of 51 patients with glaucoma and 62 age-similar control
      subjects free of eye disease. RNFL thicknesses and perimetric sensitivities were
      converted to ganglion cell numbers using the Harwerth model for perimetry and the
      Harwerth model for RNFL. These two estimates of ganglion cell number were
      compared for the inferior temporal (IT) and superior temporal (ST) sectors of the
      optic disc and the corresponding visual field locations. Comparisons were made
      with 14 visual field locations per sector (including a point in the macula for
      the inferior temporal sector) and with 13 locations (no point in the macula).
      Data for controls and patients were analysed separately, comparing mean values
      for RNFL perimetry models. Bonferroni correction was applied to control for
      repeated tests of significance. The difference between mean values for the RNFL
      and perimetry models was quantified by equating the means for controls through
      reduction of the assumed axon diameter used by the RNFL model. RESULTS: For the
      control group, the Harwerth RNFL model yielded smaller mean number of retinal
      ganglion cells than the Harwerth perimetry model, 23-47% lower (t > 13, p <
      0.0001). This corresponded to mean axon diameters from 0.48 to 0.69 MUm, with the
      smallest axons when the 14th location in the macula was included. With these new
      axon diameters, estimates of ganglion cell numbers for patients were still lower
      than for the RNFL model, by 19-28% (t > 6.5, p < 0.0001). CONCLUSIONS: The
      Harwerth RNFL model consistently gave lower ganglion cell numbers than the
      Harwerth perimetry model, and this discordance persisted in patients even after
      reducing assumed axon diameter for controls. This finding contradicts the
      assumptions of the Medeiros structure-function index.

PMID- 25604957
TI  - Experimental approaches for elucidating co-agonist regulation of NMDA receptor in
      motor neurons: Therapeutic implications for amyotrophic lateral sclerosis (ALS).
AB  - Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterised by
      selective loss of motor neurons leading to fatal paralysis. Although most cases
      are sporadic, approximately 10% of cases are familial and the identification of
      mutations in these kindred has greatly accelerated our understanding of disease
      mechanisms. To date, the causal genes in over 70% of these families have been
      identified. Recently, we reported a mutation (R199W) in the enzyme that degrades
      d-serine, D-amino acid oxidase (DAO) and co-segregates with disease in familial
      ALS. Moreover, D-serine and DAO are abundant in human spinal cord and severely
      depleted in ALS. Using cell culture models, we have defined the effects of R199W
      DAO, and shown that it activates autophagy, leads to the formation of
      ubiquitinated protein aggregates and promotes apoptosis, all of which processes
      are attenuated by a D-serine/glycine site antagonist of the N-methyl D-aspartate
      receptor (NMDAR). These findings suggest that the toxic effects of R199W-DAO are
      at least in part mediated via the NMDAR involving the D-serine/glycine site and
      that an excitotoxic mechanism may contribute to disease pathogenesis.

PMID- 25604958
TI  - Development of lipoprotein(a) siRNAs for mechanism of action studies in non-human
      primate models of atherosclerosis.
AB  - Lipoprotein(a) [Lp(a)] has recently been recognized as an independent risk factor
      for coronary heart disease. While plasma Lp(a) levels are correlated with
      cardiovascular risk, the mechanism by which this particle contributes to
      atherosclerosis is largely unknown. Although humanized transgenic mouse model has
      recently been described to study Lp(a) biology, non-human primates (NHP) are the
      only preclinical model available that allow study of the role of Lp(a) in
      atherosclerosis in an innate setting. We describe targeting of LPA using lipid
      nanoparticle formulated short interfering RNAs (siRNAs) in lean rhesus macaque
      monkeys. We show >90 % LPA mRNA lowering in the liver and >95 % Lp(a) plasma
      reduction for over 3 weeks after a single siRNA dose. Given the potency of LPA
      siRNAs, siRNA approach may enable chronic reduction of Lp(a) in atherosclerotic
      NHP and help to unmask the role for Lp(a) in the genesis and progression of
      atherosclerosis in man. 

PMID- 25604959
TI  - Guidelines for translational research in heart failure.
AB  - Heart failure (HF) remains a major cause of death and hospitalization worldwide.
      Despite medical advances, the prognosis of HF remains poor and new therapeutic
      approaches are urgently needed. The development of new therapies for HF is
      hindered by inappropriate or incomplete preclinical studies. In these guidelines,
      we present a number of recommendations to enhance similarity between HF animal
      models and the human condition in order to reduce the chances of failure in
      subsequent clinical trials. We propose different approaches to address safety as
      well as efficacy of new therapeutic products. We also propose that good practice
      rules are followed from the outset so that the chances of eventual approval by
      regulatory agencies increase. We hope that these guidelines will help improve the
      translation of results from animal models to humans and thereby contribute to
      more successful clinical trials and development of new therapies for HF. 

PMID- 25604963
TI  - Group VI metal complexes of tris(diphenylphosphinomethyl)phenylborate: modulation
      of ligand donation via coordination of M(CO)3 units at the borate phenyl
      substituent.
AB  - A series of d(6) metal complexes of tris(diphenylphosphinomethyl)phenylborate
      ([PhB(CH2PPh2)3](-), PhBP3), including [Et4N][M(CO)3(PhBP3)] (M = Cr, Mo, W),
      inaugural group VI metal tris(phosphino)borate complexes, and zwitterionic
      Mn(CO)3(PhBP3) have been synthesized and fully characterized. An analysis of IR
      nu(CO) data for [Et4N][M(CO)3(PhBP3)] indicates that PhBP3 is significantly less
      strongly donating than Tp towards zerovalent M(CO)3 fragments; PhBP3 does not
      function as a strongly donating scorpionate in this system as its does towards
      cationic metal fragments suggesting that PhBP3 may not function as an effective
      surrogate of hydrotris(1-pyrazolyl)borate towards zerovalent metals. While the
      metal centers of [Et4N][M(CO)3(PhBP3)] are very likely still more electron-rich
      than those of M(CO)3(triphos), the anions of [Et4N][M(CO)3(PhBP3)] do not provide
      robust oxidative addition products analogous to those of M(CO)3(triphos). A new
      bi-functional role for PhBP3 was investigated via the synthesis of seven
      structurally characterized bimetallics in which zerovalent M(CO)3 and monovalent
      [Mn(CO)3](+) fragments bind the three phosphine atoms and the borate phenyl
      substituent. IR nu(CO) data support modest attenuation of PhBP3 donor ability at
      phosphorus upon eta(6)-phenyl substituent binding, representing a new inductive
      strategy for tuning tris(phosphino)phenylborate donation at the kappa(3)
      phosphine-bound metal fragment. 

PMID- 25604960
TI  - Function of CD147 in atherosclerosis and atherothrombosis.
AB  - CD147, a member of the immunoglobulin super family, is a well-known potent
      inducer of extracellular matrix metalloproteinases. Studies show that CD147 is
      upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory
      disease of the artery wall. Further understanding of the functions of CD147 in
      atherosclerosis and atherothrombosis may provide a new strategy for preventing
      and treating cardiovascular disease. In this review, we discuss how CD147
      contributes to atherosclerosis and atherothrombosis. 

PMID- 25604964
TI  - On the molecular basis of the high affinity binding of basic amino acids to
      LAOBP, a periplasmic binding protein from Salmonella typhimurium.
AB  - The rational designing of binding abilities in proteins requires an understanding
      of the relationship between structure and thermodynamics. However, our knowledge
      of the molecular origin of high-affinity binding of ligands to proteins is still
      limited; such is the case for l-lysine-l-arginine-l-ornithine periplasmic binding
      protein (LAOBP), a periplasmic binding protein from Salmonella typhimurium that
      binds to l-arginine, l-lysine, and l-ornithine with nanomolar affinity and to l
      histidine with micromolar affinity. Structural studies indicate that ligand
      binding induces a large conformational change in LAOBP. In this work, we studied
      the thermodynamics of l-histidine and l-arginine binding to LAOBP by isothermal
      titration calorimetry. For both ligands, the affinity is enthalpically driven,
      with a binding DeltaCp of ~-300 cal mol(-1)  K(-1) , most of which arises from
      the burial of protein nonpolar surfaces that accompanies the conformational
      change. Osmotic stress measurements revealed that several water molecules become
      sequestered upon complex formation. In addition, LAOBP prefers positively charged
      ligands in their side chain. An energetic analysis shows that the protein
      acquires a thermodynamically equivalent state with both ligands. The 1000-fold
      higher affinity of LAOBP for l-arginine as compared with l-histidine is mainly of
      enthalpic origin and can be ascribed to the formation of an extra pair of
      hydrogen bonds. Periplasmic binding proteins have evolved diverse energetic
      strategies for ligand recognition. STM4351, another arginine binding protein from
      Salmonella, shows an entropy-driven micromolar affinity toward l-arginine. In
      contrast, our data show that LAOBP achieves nanomolar affinity for the same
      ligand through enthalpy optimization.

PMID- 25604962
TI  - Tumor-targeting novel manganese complex induces ROS-mediated apoptotic and
      autophagic cancer cell death.
AB  - In this study, the antitumor activity of the novel manganese (II) compound, Adpa
      Mn {[(Adpa)Mn(Cl)(H(2)O)] (Adpa=bis(2-pyridylmethyl)amino-2-propionic acid)}, and
      its possible mechanisms of action were investigated. In vitro, the growth
      inhibitory effects of Adpa-Mn (with IC(50) values lower than 15 uM) on tumor cell
      lines were examined by MTT assay. We found that this compound was more selective
      against cancer cells than the popular chemotherapeutic reagent, cisplatin. We
      then found that Adpa-Mn achieved its selectivity against cancer cells through the
      transferrin (Tf)-transferrin receptor (TfR) system, which is highly expressed in
      tumor cells. Furthermore, Adpa-Mn induced both apoptosis and autophagy, as
      indicated by chromatin condensation, the activation of poly(ADP-ribose)
      polymerase (PARP), Annexin V/propidium iodide staining, an enhanced fluorescence
      intensity of monodansylcadaverine (MDC), as well as the elevated expression of
      the autophagy-related protein, microtubule-associated protein 1 light chain 3
      (LC3). In addition, Adpa-Mn induced the generation of intracellular reactive
      oxygen species (ROS) and its anticancer effects were significantly reduced
      following pre-treatment with the antioxidant, N-acetyl cysteine, indicating that
      ROS triggered cell death. In vivo, the induction of apoptosis and autophagy in
      tumor tissue was confirmed following treatment with Adpa-Mn, which contributed to
      its significant antitumor activity against hepatocellular carcinoma (Hep-A cell)
      xenografts at 10 mg/kg. Taken together, these data suggest the possible use of
      Adpa-Mn as a novel anticancer drug.

PMID- 25604965
TI  - Abscisic acid negatively interferes with basal defence of barley against
      Magnaporthe oryzae.
AB  - BACKGROUND: Plant hormones are well known regulators which balance plant
      responses to abiotic and biotic stresses. We investigated the role of abscisic
      acid (ABA) in resistance of barley (Hordeum vulgare L.) against the plant
      pathogenic fungus Magnaporthe oryzae. RESULTS: Exogenous application of ABA prior
      to inoculation with M. oryzae led to more disease symptoms on barley leaves. This
      result contrasted the finding that ABA application enhances resistance of barley
      against the powdery mildew fungus. Microscopic analysis identified diminished
      penetration resistance as cause for enhanced susceptibility. Consistently, the
      barley mutant Az34, impaired in ABA biosynthesis, was less susceptible to
      infection by M. oryzae and displayed elevated penetration resistance as compared
      to the isogenic wild type cultivar Steptoe. Chemical complementation of Az34
      mutant plants by exogenous application of ABA re-established disease severity to
      the wild type level. The role of ABA in susceptibility of barley against M.
      oryzae was corroborated by showing that ABA application led to increased disease
      severity in all barley cultivars under investigation except for the most
      susceptible cultivar Pallas. Interestingly, endogenous ABA concentrations did not
      significantly change after infection of barley with M. oryzae. CONCLUSION: Our
      results revealed that elevated ABA levels led to a higher disease severity on
      barley leaves to M. oryzae. This supports earlier reports on the role of ABA in
      enhancing susceptibility of rice to the same pathogen and thereby demonstrates a
      host plant-independent function of this phytohormone in pathogenicity of
      monocotyledonous plants against M. oryzae.

PMID- 25604966
TI  - Synthesis, characterization and urease inhibition, in vitro anticancer and
      antileishmanial studies of Ni(II) complexes with N,N,N'-trisubstituted thioureas.
AB  - A series of N,N,N'-trisubstituted thioureas (1-12) and their Ni(II) complexes (1a
      12a) were synthesized and characterized by multinuclear ((1)H and (13)C) NMR, FT
      IR spectroscopy and LC-MS techniques in combination with elemental analysis. The
      crystal structures of both ligands and Ni(II) chelates of type Ni(L-O, S)2 were
      determined by single crystal X-ray diffraction analysis. All the complexes were
      adopted to have square planar geometry, where the N,N,N'-trisubstituted thioureas
      showed bidentate mode of coordination at nickel centre through oxygen and sulfur
      atoms. The synthesized complexes were screened for potential inhibitors of Jack
      bean urease. Compounds 1a and 3a were observed as most potent inhibitors of
      urease exhibiting IC50 values of 1.17 +/- 0.12 and 1.19 +/- 0.41 uM,
      respectively. Cytotoxicity assay on lung carcinoma (H-157) and kidney fibroblast
      (BHK-21) cell showed that compounds were significant anticancer agents.
      Additionally, the complexes were tested against Leishmania major and found to be
      potent antileishmanial agents.

PMID- 25604967
TI  - Image quality and radiation reduction of 320-row area detector CT coronary
      angiography with optimal tube voltage selection and an automatic exposure control
      system: comparison with body mass index-adapted protocol.
AB  - To assess the image quality and radiation exposure of 320-row area detector
      computed tomography (320-ADCT) coronary angiography with optimal tube voltage
      selection with the guidance of an automatic exposure control system in comparison
      with a body mass index (BMI)-adapted protocol. Twenty-two patients (study group)
      underwent 320-ADCT coronary angiography using an automatic exposure control
      system with the target standard deviation value of 33 as the image quality index
      and the lowest possible tube voltage. For comparison, a sex- and BMI-matched
      group (control group, n = 22) using a BMI-adapted protocol was established.
      Images of both groups were reconstructed by an iterative reconstruction
      algorithm. For objective evaluation of the image quality, image noise, vessel
      density, signal to noise ratio (SNR), and contrast to noise ratio (CNR) were
      measured. Two blinded readers then subjectively graded the image quality using a
      four-point scale (1: nondiagnostic to 4: excellent). Radiation exposure was also
      measured. Although the study group tended to show higher image noise (14.1 +/-
      3.6 vs. 9.3 +/- 2.2 HU, P = 0.111) and higher vessel density (665.5 +/- 161 vs.
      498 +/- 143 HU, P = 0.430) than the control group, the differences were not
      significant. There was no significant difference between the two groups for SNR
      (52.5 +/- 19.2 vs. 60.6 +/- 21.8, P = 0.729), CNR (57.0 +/- 19.8 vs. 67.8 +/-
      23.3, P = 0.531), or subjective image quality scores (3.47 +/- 0.55 vs. 3.59 +/-
      0.56, P = 0.960). However, radiation exposure was significantly reduced by 42 %
      in the study group (1.9 +/- 0.8 vs. 3.6 +/- 0.4 mSv, P = 0.003). Optimal tube
      voltage selection with the guidance of an automatic exposure control system in
      320-ADCT coronary angiography allows substantial radiation reduction without
      significant impairment of image quality, compared to the results obtained using a
      BMI-based protocol.

PMID- 25604968
TI  - Physical Dating Violence in Spain and the United Kingdom and the Importance of
      Relationship Quality.
AB  - Mixed-gender friendships, romantic relationships, and sexual behaviors increase
      during adolescence as a normal part of development. However, some studies have
      revealed potential risks to these types of social relationships. Different
      authors have indicated that dating violence among adolescents is an issue for
      concern. To date, there has been little research on this topic cross-nationally.
      This study examined and compared the prevalence and characteristics of physical
      dating violence among young people aged between 15 and 18 years in England and
      Spain (N = 200 in Spain, N = 199 in England), and how being involved (or not) in
      this violence relates to romantic relationship quality. Results indicated that
      approximately 23% of young people reported victimization and 30% reported
      perpetrating physical dating violence. In both countries, most of those involved
      in physical dating violence reported involvement in reciprocal violence
      (displaying both aggression and victimization). Those young people involved in
      dating violence reported higher levels on scales assessing negative aspects of
      relationship quality compared with those not involved, but there were no
      significant differences in positive aspects of relationship quality. Furthermore,
      different patterns appeared relating to the severity of violence and country. The
      findings are discussed in terms of their implications for theory and practice.

PMID- 25604969
TI  - Relationships Between Sport Participation, Problem Alcohol Use, and Violence: A
      Longitudinal Study of Young Adults in Australia.
AB  - There is a growing body of evidence suggesting a link between sport participation
      and violent behavior outside of the sporting context. However, there have been
      few studies that have investigated the basis of this relationship. The current
      study examined longitudinal relationships between sport participation, problem
      alcohol use, and various violent behaviors, and whether sport participation
      moderates relationships between problem alcohol use and violence. The sample
      comprised 2,262 young adults (55% female, age range at Time 1 = 17-24 years) from
      Victoria, Australia, surveyed in 2010 and 2012. When controlling for common risk
      factors, substance use, and past violence, sport participation was not associated
      with any violent behaviors 2 years later. However, sport participation moderated
      the relationship between problem alcohol use and fighting, whereby problem
      alcohol use was associated with engaging in fights 2 years later for sport
      participants, but not for nonparticipants. These findings suggest that it is not
      sport participation per se that influences later violence but the drinking norms
      or culture embedded within certain sporting contexts. Prevention approaches that
      address the drinking culture and social approval of excessive alcohol consumption
      within sporting contexts may reduce the incidence of violent behavior in the
      community. 

PMID- 25604970
TI  - Similar Mechanisms? A Comparative Longitudinal Study of Adolescent Violence and
      Victimization.
AB  - This study analyzes the extent to which there are similar patterns of violent
      offending and victimization in a panel of adolescents. Three explanatory
      perspectives are assessed: population heterogeneity, state dependence, and a
      mixed model. Data are drawn from a four-wave panel study of 3,976 adolescents.
      The main study measures comprise self-report indices for victimization and
      delinquency. Theoretical perspectives are specified through three distinct
      statistical approaches--latent growth curve, autoregressive simplex, and
      autoregressive latent trajectory (ALT) models. The analysis then incorporates the
      effects of relevant time-stable and time-varying influences. A mixed perspective,
      represented by the ALT model, best fits the data for both violent victimization
      and offending. Covariates drawn from the two perspectives have similar effects as
      well. The findings provide some support for a similar mechanisms hypothesis.

PMID- 25604971
TI  - Are Interpersonal Violence Rates Higher Among Young Women in College Compared
      With Those Never Attending College?
AB  - Estimates of sexual violence and partner violence rates among young women are
      generated primarily from college samples. Few studies have data to compare rates
      among similar-aged women attending college with those who never attended college.
      This study aims to estimate rates of partner violence by type (sexual, physical,
      and psychological) and severity (mild, moderate, severe), sexual harassment, and
      knowing or suspecting that someone put a drug in a drink (drugged drink) among a
      national sample of 959 young women aged 18 to 24 in an intimate relationship in
      the past 12 months who were either currently in college (college;n= 272) or never
      attended college (non-college;n= 687). After adjusting for demographic
      differences between these two groups, no significant differences were found in
      rates of sexual partner violence (28.4% non-college, 23.5% college), physical
      partner violence (27.9% non-college, 26.3% college), psychological partner
      violence (Mscore: 6.10 non-college, 5.59 college), sexual harassment (15.5% non
      college, 14.1% college), or drugged drink (8.5% non-college, 7.8% college).
      Finding high rates of interpersonal violence among young women who are and are
      not currently attending college indicates the need to target all young adults
      with violence prevention interventions in educational, workplace, and other
      community-based settings. 

PMID- 25604972
TI  - ADAM "sequence" part II: hypothesis and speculation.
AB  - Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766;
      Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions,
      mutilations (ADAM) sequence remains causally and pathogenetically incognito. In
      1930 Streeter stated " apodictically" that no evidence has been found that intra
      uterine amputation is due to amniotic bands or adhesions ..." and that his 16
      cases provided (histological) evidence for a "germinal origin." He concluded that
      an amniotic cord was "not an adhesion or inflammatory product but ... an
      anomalous developmental structure and present from the outset." In survivors the
      "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958,
      Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or
      "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions
      ... are always produced by ... the fetus - as a result of dysplasia in foetal
      tissues. They are the result, not the cause, of foetal malformations." Streeter
      [1930] mentions a potential familial case (56-year-old man and his mother), not
      controlled by photographs or other records and concluded "that the (ADAM)
      deformity is not easily transmissible," but "due to the constitution of the germ
      plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that
      "... proof of amnion rupture without damage to the chorionic sac is no longer "in
      question." Considering Torpin's decades-long study of the ADAM phenomenon and
      review of 494 references (missing many) it is surprising that he does not discuss
      the relationship between the apparent ADAM defects and other, internal anomalies
      that maybe present in an affected fetus or infant not evidently caused by the
      amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our
      review of these internal and other presumed primary malformations in ADAM is
      ongoing. However, on a preliminary basis, it seems likely to us that: (1) there
      is an increased prevalence of such primary anomalies in the ADAM condition
      confirming the view and experience of others, for example Czeizel et al. [1993];
      (2) these malformations (e.g., heterotaxy) may arise as early as gastrulation;
      (3) that, given the ADAM phenomenon is exclusively ascertained as the ADAM
      phenotype in fetuses and infants, that is, that its cause and ascertainment are
      completely congruent, then the apparent amniotic defect must also be regarded as
      a malformation; (4) that in such a case the ADAM phenomenon with associated
      primary malformation(s) is a form of syndromal pleiotropy due to one cause yet to
      be elucidated. To that end we recommend archiving DNA from all affected fetuses
      coming to autopsy and their parents and placentas and surgical tissues of all
      viable affected infants for ultimate exome or genome sequencing perhaps with
      special attention to the syncytin genes.

PMID- 25604973
TI  - Pharmacokinetic and pharmacodynamic evaluation of macitentan , a novel endothelin
      receptor antagonist for the treatment of pulmonary arterial hypertension.
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a chronic disorder of the
      pulmonary vasculature characterized by elevated mean pulmonary arterial pressure
      eventually leading to right-sided heart failure and premature death. Macitentan
      is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with
      high affinity and sustained receptor binding that was approved in the USA,
      Europe, Canada, and Switzerland for the treatment of PAH. AREAS COVERED: This
      review discusses the pharmacokinetics (PK) and pharmacodynamics (PD) of
      macitentan and its drug interaction potential based on preclinical and clinical
      data. EXPERT OPINION: Up to date, macitentan is the only registered treatment for
      PAH that significantly reduced morbidity and mortality as a combined endpoint in
      a long-term event-driven study. The safety profile of macitentan is favorable
      with respect to hepatic safety and edema/fluid retention and may be better than
      that of other ET receptor antagonists such as bosentan and ambrisentan. The PK
      profile supports a once-a-day dosing regimen. Macitentan has limited interactions
      with other drugs. Based on these characteristics macitentan is an important new
      addition to the treatment of PAH.

PMID- 25604974
TI  - An audit of newborn screening procedure: impact on infants presenting clinically
      before results are available.
AB  - BACKGROUND AND OBJECTIVE: Tandem mass spectrometry-based newborn screening (NBS)
      is a powerful screening tool. The NBS process includes sample collection,
      shipment, testing, analysis, reporting and communication with the infant's
      family. We explored the NBS programme-related factors that may delay diagnosis
      and may influence timely initiation of treatment in neonates who present before
      the screening results are available and therefore urgently need diagnosis and
      treatment. STUDY DESIGN: Detailed retrospective review of all data regarding
      sampling, shipment, testing and notification, contact with family and initiation
      of treatment of all neonates with disorders of fatty acid oxidation (FAO) and
      protein metabolism (PM), who presented clinically before NBS results were
      available, between 1-February-2002 and 31-January-2014. RESULTS: Of 847,418
      newborns screened, 18 infants presented clinically before NBS results were
      available (FAO n = 9, median age 2.5 days; PM n = 9, median age 3 days). Samples
      were collected from 11 infants at age 48-72 h, as per instructions, and were
      received in the laboratory at a median age of 7 days (median 4 days from sample
      collection until receipt in the laboratory). Results were available within 24h in
      16/18 infants. Treatment for a suspected metabolic disorder was initiated in
      seven infants before results were available. CONCLUSIONS: An audit of the
      programme procedures enabled the identification of issues that can be improved.
      Some patients benefited from the availability of results shortly after
      presentation. Good communication between the laboratory, the clinical metabolic
      specialist service and the primary treating team ensures timely initiation of
      treatment in these infants.

PMID- 25604975
TI  - Capacity building in public health nutrition.
AB  - The aim of the present paper is to review capacity building in public health
      nutrition (PHN), the need for which has been stressed for many years by a range
      of academics, national and international organisations. Although great strides
      have been made worldwide in the science of nutrition, there remain many problems
      of undernutrition and increasingly of obesity and related chronic diseases. The
      main emphasis in capacity building has been on the nutrition and health
      workforce, but the causes of these health problems are multifactorial and require
      collaboration across sectors in their solution. This means that PHN capacity
      building has to go beyond basic nutrition and beyond the immediate health
      workforce to policy makers in other sectors. The present paper provides examples
      of capacity building activities by various organisations, including universities,
      industry and international agencies. Examples of web-based courses are given
      including an introduction to the e-Nutrition Academy. The scope is international
      but with a special focus on Africa. In conclusion, there remains a great need for
      capacity building in PHN but the advent of the internet has revolutionised the
      possibilities. 

PMID- 25604976
TI  - Atomic layer etching of Al2O3 using sequential, self-limiting thermal reactions
      with Sn(acac)2 and hydrogen fluoride.
AB  - The atomic layer etching (ALE) of Al2O3 was demonstrated using sequential, self
      limiting thermal reactions with tin(II) acetylacetonate (Sn(acac)2) and hydrogen
      fluoride (HF) as the reactants. The Al2O3 samples were Al2O3 atomic layer
      deposition (ALD) films grown using trimethylaluminum and H2O. The HF source was
      HF-pyridine. Al2O3 was etched linearly with atomic level precision versus number
      of reactant cycles. The Al2O3 ALE was monitored at temperatures from 150 to 250 
      degrees C. Quartz crystal microbalance (QCM) studies revealed that the sequential
      Sn(acac)2 and HF reactions were self-limiting versus reactant exposure. QCM
      measurements also determined that the mass change per cycle (MCPC) increased with
      temperature from -4.1 ng/(cm(2) cycle) at 150  degrees C to -18.3 ng/(cm(2)
      cycle) at 250  degrees C. These MCPC values correspond to etch rates from 0.14
      A/cycle at 150  degrees C to 0.61 A/cycle at 250  degrees C based on the Al2O3
      ALD film density of 3.0 g/cm(3). X-ray reflectivity (XRR) analysis confirmed the
      linear removal of Al2O3 and measured an Al2O3 ALE etch rate of 0.27 A/cycle at
      200  degrees C. The XRR measurements also indicated that the Al2O3 films were
      smoothed by Al2O3 ALE. The overall etching reaction is believed to follow the
      reaction Al2O3 + 6Sn(acac)2 + 6HF -> 2Al(acac)3 + 6SnF(acac) + 3H2O. In the
      proposed reaction mechanism, the Sn(acac)2 reactant donates acac to the substrate
      to produce Al(acac)3. The HF reactant allows SnF(acac) and H2O to leave as
      reaction products. The thermal ALE of many other metal oxides using Sn(acac)2 or
      other metal beta-diketonates, together with HF, should be possible by a similar
      mechanism. This thermal ALE mechanism may also be applicable to other materials
      such as metal nitrides, metal phosphides, metal sulfides and metal arsenides. 

PMID- 25604977
TI  - Trends in infant mortality rates in Hungary between 1963 and 2012.
AB  - AIM: This study investigated annual and seasonal death trends for infants of <1
      year of age in Hungary between 1963 and 2012 and analysed commonly accepted risk
      factors. METHODS: Data on the numbers of live births and infant deaths were
      obtained from the published nationwide population register. Negative binomial
      regression was applied to investigate the yearly trends in rates and also the
      effect of possible risk factors - low birthweight, maternal education and sex -
      on infant mortality. Cyclic trends were investigated using logistic regression.
      RESULTS: Annual infant mortality declined significantly (p < 0.001) from 42.9 to
      4.9 per 1000 live births per year during the study period and significantly
      increased (p < 0.001) in the low birthweight group and lower maternal education
      groups. A significant (p < 0.001) cyclic trend in mortality was revealed, with a
      peak in deaths in late February for all infants and a double peak, in May and
      November, in the group of cases who died during the early neonatal period.
      CONCLUSION: This Hungarian study suggests that there was a significant seasonal
      effect on neonatal and infant mortality at the end of winter between 1963 and
      2012. We speculate that this may have been related to respiratory infections.

PMID- 25604978
TI  - [Phyllodes breast tumors].
AB  - INTRODUCTION: Phyllodes tumour is a breast tumour occurring very rarely. It
      accounts for only in 1% of all cases of breast tumour. The diagnosis of phyllodes
      tumours can be difficult in consideration of the small number of cases. Treatment
      of phyllodes tumours is always surgical. METHODS: In 2004-2013, we operated on
      twelve female patients with phyllodes tumours out of the total number of 1564
      surgeries for breast tumours (0.8%) at the Department of Surgery at Teaching
      Hospital in Pilsen. We evaluated the age, the biological behaviour of the tumour
      depending on the tumour size and duration, the distant metastases, therapy and
      survival. RESULTS: The average age at the time of surgery was fifty years (2684),
      the duration of disease to the surgical solution ranged from one month to ten
      years. Tumour size was in the range of two to twenty-nine centimetres, tumours
      measuring less than five centimetres were always benign. Tumour excision for
      benign phyllodes tumour was performed seven times. Malignant phyllodes tumour was
      diagnosed five times with mastectomy performed in each case, and the axilla was
      exenterated in three cases where nodes were benign in each of them. In one case,
      mastectomy was followed by radiotherapy because the tumour reached the edge of
      the resected part; the other patients were only monitored. In two patients,
      tumour spreading into the lungs was diagnosed at five to ten months after breast
      surgery. One patient with generalized disease died, the other ones live with no
      local recurrence of this disease. Median survival is fifty-two months; the
      disease-free interval is fifty months. CONCLUSION: The results show that if
      phyllodes tumour is diagnosed in time, it is almost exclusively benign. If the
      case history is longer and the tumour is growing, the likelihood of malignancy
      increases. Surgical treatment is also sufficient in the case of malignant forms.
      The breast surgery does not need to be supplemented with exenteration of
      axilla.Key words: breast - phyllodes tumour.

PMID- 25604979
TI  - The benefit of PET/CT in the diagnosis and treatment of esophageal cancer.
AB  - INTRODUCTION: To evaluate the significance of PET/CT for the initial staging of
      esophageal cancer with emphasis on metastatic lymph node affection and detection
      of distant metastases. Furthermore, the aim of the work was to analyze the
      significance of PET/CT examination when evaluating the effect of neoadjuvant
      therapy. METHODS: A set of 354 patients with esophageal cancer treated at the 1st
      Department of Surgery, University Hospital Olomouc and Medical Faculty at Palacky
      University in Olomouc between the years 20062012 were analyzed in a prospective
      study. The initial PET/CT examination was performed in 349 patients. We analyzed
      the benefit of this examination in regard to disease staging and based on the
      result, therapeutic strategy was determined. The initial PET/CT showed varying
      degrees of disease generalization in 102 patients, these patients were indicated
      for palliative or symptomatic therapy. In 247 patients, the disease was limited
      only to the esophagus and /or regional lymph nodes. After considering the
      patients overall condition and taking into account the wishes of the patient, 188
      patients were indicated for neoadjuvant chemoradiotherapy (CRT); 32 patients did
      not complete this treatment. In 156 patients a follow-up PET/CT scan was
      performed after an average of 8.4 weeks following completion of neoadjuvant
      therapy. Based on this examination, a complete response- CR, was observed in 38
      patients (24.4%), regression of the tumor in 89 (57.0%), stationary findings were
      seen in 10 (6.4%), and progression in 19 (12.2%). Ninety-seven patients were
      indicated for surgical resection; however, esophagectomy was only possible in 85
      patients, in the remaining 12 patients only an explorative laparotomy was
      performed due to disease progression. RESULTS: The initial PET/CT examination
      performed in 349 patients correctly described the extent of the disease in
      accordance with the histologically confirmed diagnosis in virtually all patients.
      A false positive result was seen in only 5 patients (1.43%). When evaluating the
      effect of neoadjuvant therapy, the patients were divided into groups based on the
      findings of the follow-up PET/CT after neoadjuvant therapy and their overall
      survival was evaluated. A significant difference (p=0.0004) in survival was
      observed between the groups based on the different reactions to neoadjuvant
      therapy (CR (n=38), regression (n=89), stationary findings (n=10), progression
      (n=19)) without taking into account the following treatment the patient received
      after neoadjuvant therapy. Patients who had a better response to neoadjuvant
      therapy had better survival results. There was also a significant difference in
      survival between the group of patients who completed neoadjuvant therapy and
      underwent radical surgical resection (n=85) versus those patients who completed
      neoadjuvant therapy but did not undergo subsequent surgery (n=59). The operated
      group had a significantly higher overall survival (p=0.003). The longest mean
      survival, 38.6 months (median 29.0 months), was achieved by the group of patients
      who completed neoadjuvant therapy, showed a complete response on the follow-up
      PET/CT, and underwent surgical resection. However, a significant difference was
      not observed (p=0.587) between the groups who underwent surgical resection and
      whose follow-up PET/CT results differed (regression or stationary findings). To
      date, the number of cases in the individual groups is not great enough to
      consider the obtained results conclusive, and we will continue to include more
      patients into the study and continue with the analysis. CONCLUSION: The work
      documents the significance and benefit of PET/CT in the initial staging of
      esophageal cancer, especially in detecting metastatic disease- positive lymph
      nodes as well as distant metastases. PET/CT has great importance in determining
      therapeutic strategy. Furthermore, the significance of PET/CT in evaluating the
      effect of neoadjuvant therapy was also studied.Key words: esophageal cancer
      PET/CT neoadjuvant therapy esophagectomy.

PMID- 25604980
TI  - Strategies of treatment of chest wall tumors and our experience.
AB  - INTRODUCTION: The only curative treatment of tumors of the chest wall (primary or
      secondary),despite all the progress in oncological therapy, is a surgical radical
      resection. The goal of the paper is the identification of a complication
      occurring after chest wall resections for a tumor (evaluation of morbidity and
      mortality). Furthermore, the tumor type and employed reconstruction method were
      analyzed. METHODS: A group of patients who underwent resection of the chest wall
      for primary or secondary tumors at the 1st Dept. Of Surgery, University Hospital
      Olomouc, was retrospectively analyzed. Age, diagnosis, procedure, histopathology
      of the tumor, preoperative and postoperative oncological treatment, preoperative
      co-morbidities, postoperative complications, the use of artificial lung
      ventilation and recurrences were recorded for all patients. RESULTS: 57 patients
      aged 16 to 86 years underwent a chest wall resection, 51% for a primary tumor and
      49% for a secondary tumor. Resection of at least one rib or partial resections of
      the sternum were performed in every patient. Reconstruction with a mesh was
      employed in 22 patients; in 10 patients the mesh was covered with a muscle flap.
      Postoperative complications occurred in 10 patients (17.5%). CONCLUSION: It is
      necessary to follow the basic principles of treatment of chest wall tumors;
      therefore surgery of these tumors should be concentrated to specialized centers.
      Always before surgery, diagnosis should be established by means of a biopsy and
      generalization of the disease should be excluded, ideally using PET/CT. Most
      important for successful treatment is experience and interdisciplinary
      cooperation of the team. This results in a low mortality and morbidity rate,
      which was confirmed by our results. KEYWORDS: chest wall tumors chest
      reconstruction sternum resection - treatment of chest wall tumors chondroma.

PMID- 25604981
TI  - [Breast cancer at the 1st Surgical Department, University Hospital Olomouc
      assessing the number and age of patients and benefit of breast screening].
AB  - INTRODUCTION: Breast cancer is the most common malignancy in women. It affects
      mostly women between the ages of 60 and 70; however, in the past years, the
      number of younger female patients has been increasing. The incidence of breast
      cancer has been rising worldwide, especially in the United States and Western
      Europe. Breast carcinoma mortality, on the other hand, has shown a slight
      decrease due to early screening programmes and advanced treatment methods.
      METHODS: We included patients who had undergone surgery for breast carcinoma in
      the 1st Department of Surgery at Teaching Hospital in Olomouc between 1 January
      2008 and 31 December 2012. In each patient, her age at the time of
      diagnosis/surgery was calculated. All patients were divided into 10-year age
      groups. At the same time, a sub-group of breast cancer patients younger than 45
      years was created. We compared the numbers of patients in the respective groups
      and sub-groups in every year. The mean age and the median of age were also
      calculated. To evaluate the benefit of mammary screening, we compared the staging
      of operated tumours in the different years studied. The results were
      statistically processed and evaluated. RESULTS: The total number of 980 patients
      underwent surgery for breast carcinoma at our department between 2008 and 2012
      with age ranging from 20 to 88 years. 101 of them were younger than 45 years. The
      mean age of the patients was 59 years, the median was 60 years. The total number
      of patients increased from 153 in 2008 to 240 in 2012. There was no significant
      increase in the number of patients younger than 45 years. There were more
      patients diagnosed with stage II carcinoma and fewer patients with stage III
      carcinoma in 2012 than in 2010. CONCLUSION: The analysis of our group of patients
      confirmed the increasing tendencies of breast cancer incidence in total. We did
      not prove a statistically significant increase in the number of patients in pre
      screening age (i.e., younger than 45 years). More frequent diagnosis of early
      stage disease was detected, especially during the last three evaluated years.Key
      words: breast cancer - age - stage screening.

PMID- 25604982
TI  - [Intramural haematoma of the oesophagus - a case report and literature review].
AB  - Intramural hematoma of the oesophagus is a rare diagnosis presenting with
      retrosternal pain, dysphagia and haematemesis. It is caused by barotrauma or
      direct injury to the esophagus, or it may occur spontaneously without apparent
      cause, which is more common in patients taking antiplatelet or anticoagulant
      medications. In most cases, treatment is conservative. Rarely, endoscopic,
      endovascular or surgical treatment is effective. This article presents a case
      report of a female patient with spontaneous haematoma of the oesophagus solved
      conservatively and discusses further possibilities of the course and treatment of
      the disease.Key words: intramural haematoma of the oesophagus IHE. 

PMID- 25604983
TI  - [Swimming pool suction injury: etiology, profylaxis and management].
AB  - Swimming pool suction injuries are unique and rare with a substantive risk of
      fatal consequences. Little children under the age of 8 are the most frequent
      victims with serious injuries. Drownings of different seriousness are also a
      usual part of accidents. The case of a 19 year old man trapped in the gluteal
      area by a unsecured suction drainage hole illustrates the uniqueness of this
      problem in an interesting way. Prophylactic arrangements are well known but the
      problem is with their strict application. Fatal causes excluding drowning include
      hypovolemic shock from the sudden redistribution of intersticial fluid and blood
      and also the evisceration of the bowel and other abdominal organs. Localised
      often bizarre and large swellings and sufusions can be treated nonoperatively in
      the vast majority of cases. For the prevention of these injuries it is important
      to inform the public and increase their awareness to these injuries. It is also
      crucial for the correct management of these injuries a deeper awareness of this
      issue and a sharing of experiences and solutions with other experts.Key words:
      vacuum - accident - entrapment - compartment syndrome. 

PMID- 25604984
TI  - Hydraulic experiments for determination of in-situ hydraulic conductivity of
      submerged sediments.
AB  - A new type of in-situ hydraulic permeameter was developed to determine vertical
      hydraulic conductivity (VHC) of saturated sediments from hydraulic experiments
      using Darcy's law. The system allows water to move upward through the porous
      media filled in the permeameter chamber driven into sediments at water-sediment
      interface. Darcy flux and hydraulic gradient can be measured using the system,
      and the VHC can be determined from the relationship between them using Darcy's
      law. Evaluations in laboratory and in field conditions were performed to see if
      the proposed permeameter give reliable and valid measures of the VHC even where
      the vertical flow at water-sediment interface and fluctuation of water stage
      exist without reducing the accuracy of the derived VHC. Results from the
      evaluation tests indicate that the permeameter proposed in this study can be used
      to measure VHC of saturated sandy sediments at water-sediment interface in stream
      and marine environment with high accuracy. 

PMID- 25604985
TI  - Building policy-making capacity in the Ministry of Health: the Kazakhstan
      experience.
AB  - BACKGROUND: Recent economic growth in Kazakhstan has been accompanied by slower
      improvements in population health and this has renewed impetus for health system
      reform. Strengthening strategic planning and policy-making capacity in the
      Ministry of Health has been identified as an important priority, particularly as
      the Ministry of Health is leading the health system reform process. CASE
      DESCRIPTION: The intervention was informed by the United Nations Development
      Programme (UNDP) framework for capacity building which views capacity building as
      an ongoing process embedded in local institutions and practices. In response to
      local needs extra elements were included in the framework to tailor the capacity
      building programme according to the existing policy and budget cycles and
      respective competence requirements, and link it with transparent career
      development structures of the Ministry of Health. This aspect of the programme
      was informed by the institutional capability assessment model used by the United
      Kingdom National Health Service (NHS) which was adapted to examine the specific
      organizational and individual competences of the Ministry of Health in
      Kazakhstan. DISCUSSION AND EVALUATION: There were clear successes in building
      capacity for policy making and strategic planning within the Ministry of Health
      in Kazakhstan, including better planned, more timely and in-depth responses to
      policy assignments. Embedding career development as a part of this process was
      more challenging. This case study highlights the importance of strong political
      will and high level support for capacity building in ensuring the sustainability
      of programmes. It also shows that capacity-building programmes need to ensure
      full engagement with all local stakeholders, or where this is not possible,
      programmes need to be targeted narrowly to those stakeholders who will benefit
      most, for the greatest impact to be achieved. In sum, high quality tailor-made
      capacity development programmes should be based on thorough needs assessment of
      individual and organizational competences in a specific institutional setting.
      CONCLUSIONS: The experience showed that complementary approaches to human
      resource development worked effectively in the context of organizations and
      systems, where an enabling environment was present, and country ownership and
      political will was complemented by strong technical assistance to design and
      deliver high quality tailor-made capacity building initiatives.

PMID- 25604986
TI  - Tuberculosis risk factors among tuberculosis patients in Kampala, Uganda:
      implications for tuberculosis control.
AB  - BACKGROUND: Slow decline in the incidence of tuberculosis (TB) has been observed
      in most high TB burden countries. Knowledge of the prevalence of different TB
      risk factors can help expand TB control strategies. However with the exception of
      Human Immunodeficiency Virus (HIV) the prevalence of the other TB risk factors
      are poorly studied in Uganda. We aimed to determine the prevalence of different
      TB risk factors and TB disease presentation among TB patients in Kampala Uganda.
      METHODS: We assessed 365 adult TB patients and used descriptive statistics to
      summarize their socio-demographic, clinical, radiological, sputum
      mycobacteriology and TB risk factors (HIV, diabetes, TB contact, alcohol use,
      tobacco smoking, poverty and overcrowding) data. RESULTS: A total of 158 (43.3%)
      patients were male and the median age was 29 (IQR 28-30). Majority of the
      patients (89.2%) had pulmonary TB, 86.9% were new and 13.2% were retreatment.
      Wasting (i.e. body mass index of <18.5 kg/m(2)) was found in 38.5% of the
      patients and 63% presented with cough. Constitutional symptoms (fever, anorexia,
      night sweats and weight loss) were reported by 32.1%. Most patients (78.6%)
      presented with non-cavity lung parenchyma disease (infiltrates, nodules, masses)
      but 35.2% had cavity disease. Pleural disease was detected in 19.3% of patients.
      Positive smear microscopy and culture (irrespective of month of treatment) was
      found in 52.7% and 36.5% of patients respectively. Any drug resistance was
      detected in 21.1% of patients while multidrug resistance (MDR) TB defined as
      resistance to rifampicin and isoniazid was detected in 6.3% of patients. All MDR
      patients were new patients. The prevalence of TB risk factors were as follows:
      HIV 41.4%, diabetes 5.4%, close contact 11.5%, family history 17.5%, smoking
      26.37%, poverty 39.5%, overcrowding 57.3% and alcohol use 50.7%. Overcrowding
      increased smear positive rate, prevalence ratio 1.22, p = 0.09 but all the other
      studied risk factors did not affect clinical, radiological and
      mycobacteriological study patient characteristics. CONCLUSIONS: Among TB patients
      in Kampala, Uganda, there is high prevalence of the known TB risk factors.
      Targeting reducing their prevalence may lead to better TB control in the country.
      Tuberculosis, risk factors, Uganda.

PMID- 25604988
TI  - Development of high oleic oil crop platform in flax through RNAi-mediated
      multiple FAD2 gene silencing.
AB  - KEY MESSAGE: Simultaneous gene silencing of both FAD2 genes in high linoleic acid
      flax leads to high level of oleic acid, which is stable across multiple
      generations. High oleic oil is one of the preferred traits in oil crop
      engineering due to its stability and multiple applications as an industrial
      feedstock. Flax possesses two isoforms of FAD2 enzymes that desaturate
      monounsaturated oleic acid to polyunsaturated linoleic acid. These two enzymes
      are encoded by two FAD2 genes. By simultaneous gene silencing both FAD2 genes in
      high linoleic acid flax, Linola, high level of oleic acid up to 80% was achieved
      in 69 silencing lines. The high oleic trait was stable across multiple
      generations with oleic acid reaching up to 77% in homozygote T3 progeny. The RNAi
      mediated gene-silencing approach generated high oleic linseed oil, as well as a
      high oleic platform that can be exploited for further fatty acid engineering.

PMID- 25604989
TI  - Characterization of a new class of blue-fluorescent lipid droplet markers for
      live-cell imaging in plants.
AB  - KEY MESSAGE: The present work demonstrates the use and advantages of novel, live
      cell permeable, lipid droplet localizing, non toxic, blue fluorochromes for use
      in live plant cells. Lipid droplets (LDs) are ubiquitous components of both
      animal and plant cells. They consist of a core of neutral lipids surrounded by a
      monolayer of phospholipids, glycolipids and/or sterols with embedded amphipathic
      proteins. Although initially considered to be simple energy depots, they have
      recently emerged as organelles that serve important regulatory functions. Here we
      report three new fluorochromes as markers for LDs in plants. These bright blue
      fluorochromes with their unique spectral properties can easily be combined with
      other green and red fluorescent reporters for multicolor fluorescence imaging.
      The fluorochromes are non-toxic and photo-stable. All in all, they represent a
      reliable tool to use, for the investigation of dynamic LD biology within living
      plant cells using fluorescence microscopy.

PMID- 25604990
TI  - TaUBA, a UBA domain-containing protein in wheat (Triticum aestivum L.), is a
      negative regulator of salt and drought stress response in transgenic Arabidopsis.
AB  - KEY MESSAGE: TaUBA functions as a negative regulator of salt and drought stress
      response in transgenic Arabidopsis, either the UBA domain or the zinc finger
      domain is crucial for TaUBA's function. TaUBA (DQ211935), which is a UBA domain
      containing protein in wheat, was cloned and functionally characterized. Southern
      blot suggested that TaUBA is a low copy gene in common wheat. qRT-PCR assay
      showed that the expression of TaUBA was strongly induced by salt and drought
      stress. When suffering from drought and salt stresses, lower proline content and
      much higher MDA content in the TaUBA overexpressors were observed than those of
      the wild-type control, suggesting TaUBA may function as a negative regulator of
      salt and drought stress response in plants. To study whether the UBA domain or
      the zinc finger domain affects the function of TaUBA, TaUBADeltaUBA (deletion of
      UBA domain) and TaUBA-M (Cys464Gly and Cys467Gly) overexpression vectors were
      constructed and transformed into Arabidopsis. Upon drought and salt stresses, the
      TaUBADeltaUBA-and TaUBA-M-overexpressed plants accumulated much more proline and
      lower MDA than the wild-type control, the TaUBA-overexpressors lost water more
      quickly than TaUBADeltaUBA-and TaUBA-M-overexpressed plants as well as the wild
      type control, suggesting that overexpression of TaUBADeltaUBA or TaUBA-M improved
      the drought and salt tolerance of transgenic Arabidopsis plants and the
      possibility of ubiquitination role in the regulation of osmolyte synthesis and
      oxidative stress responses in mediating stress tolerance. qRT-PCR assay of stress
      related genes in transgenic plants upon drought and salt stresses suggested that
      TaUBA may function through down-regulating some stress related-transcription
      factors and by regulating P5CSs to cope with osmotic stress.

PMID- 25604991
TI  - Alteration of osa-miR156e expression affects rice plant architecture and
      strigolactones (SLs) pathway.
AB  - KEY MESSAGE: Overexpressing osa--miR156e in rice produced a bushy mutant and osa-
      miR156e regulation of tillering may do this through the strigolactones (SLs)
      pathway. Appropriate downregulation of osa--miR156 expression contributed to the
      improvement of plant architecture. Tillering is one of the main determinants for
      rice architecture and yield. In this study, a bushy mutant of rice was identified
      with increased tiller number, reduced plant height, prolonged heading date, low
      seed setting, and small panicle size due to a T-DNA insertion which essentially
      elevated the expression of osa-miR156e. Transgenic plants with constitutive
      expression of osa-miR156e also had the bushy phenotype, which showed osa-miR156
      may control apical dominance and tiller outgrowth via regulating the
      strigolactones signaling pathway. Furthermore, the extent of impaired morphology
      was correlated with the expression level of osa-miR156e. In an attempt to
      genetically improve rice architecture, ectopic expression of osa-miR156e under
      the GAL4-UAS system or OsTB1 promoter was conducted. According to agronomic trait
      analysis, pTB1:osa-miR156e transgenic plants significantly improved the grain
      yield per plant compared to plants overexpressing osa-miR156e, even though the
      yield was still inferior to the wild type, making it a very interesting albeit
      negative result. Our results suggested that osa-miR156 could serve as a potential
      tool for modifying rice plant architecture through genetic manipulation of the
      osa-miR156 expression level.

PMID- 25604992
TI  - Identification of genes that may regulate the expression of the transcription
      factor production of anthocyanin pigment 1 (PAP1)/MYB75 involved in Arabidopsis
      anthocyanin biosynthesis.
AB  - KEY MESSAGE: A putative RNA-binding protein with a single RNA Recognition Motif
      (At3G63450) is involved in anthocyanin biosynthesis via its ability to modulate
      the transcript level of a major positive regulator PAP1 in Arabidopsis. The R2R3
      MYB-activator production of anthocyanin pigment 1 (PAP1)/MYB75 plays a major role
      in anthocyanin biosynthesis in Arabidopsis in combination with one of three bHLH
      activators including transparent test 8 (TT8), enhancer of glabra3 (EGL3),
      glabra3 (GL3), and the WD-repeat transcription factor transparent testa 1 (TTG1),
      forming ternary MYB-basic HLH-WD40 complexes. Transcriptional activation of PAP1
      expression is largely triggered by changes in light color and intensity,
      temperature fluctuations, nutrient status, and sugar and hormone treatments.
      However, the immediate upstream and downstream regulatory factors for PAP1
      transcription are largely unknown. In the present study, using a T-DNA
      insertional mutagenesis approach, we transformed pap1-Dominant (pap1D) plants to
      modulate the levels of endogenous PAP1 transcripts. We employed Restriction Site
      Extension (RSE)-PCR analysis of 247 homogenous T3 genetic mutant lines exhibiting
      variations in anthocyanin accumulation compared to pap1D and identified 92 lines
      with T-DNA integrated in either intra- or inter-genic locations. This analysis
      revealed 80 novel candidate proteins, including a putative RNA-binding protein
      with a single RNA Recognition Motif (At3G63450), which may directly or indirectly
      regulate PAP1 expression at the transcriptional level.

PMID- 25604994
TI  - Cervicogenic headache: too important to be left un-diagnosed.
AB  - A comparison has been made between the cervicogenic headache criteria in the new
      IHS classification of headaches (3rd edition-beta version) and The Cervicogenic
      Headache International Study Group's (GHISG) criteria from 1998. In a more recent
      version, the CHISG criteria consist of 7 different items. While "core cases" of
      cervicogenic headache (CEH) usually fulfill all 7 criteria, the IHS
      classification--3rd edition beta version--fulfills only 3 criteria. Although the
      new three beta version represents an improvement from the previous one, it does
      not quite seem to live up to the expectations for a diagnostic system for
      routine, clinical use.

PMID- 25604995
TI  - Vaginal histological changes after using intravaginal sponges for oestrous
      synchronization in anoestrous ewes.
AB  - To characterize the histological and cytological vaginal changes generated by the
      use of intravaginal sponge (IS) applied in oestrous synchronization treatments in
      ewes during mid-non-breeding season. Thirty-five multiparous ewes were allocated
      to three experimental groups according to the moment in which the samples were
      taken: (i) ewes treated with IS containing 60 mg of medroxyprogesterone acetate
      for 14 days, sampled the day of IS removal (group ISR; n = 10), (ii) or after
      sponge removal at time of oestrus or 72 h after removal (group AR; n = 14) and
      (iii) ewes without sponge treatment that were sampled at the day of IS removal of
      the other groups (group CG; n = 11). Vaginal biopsies and cytological samples
      were taken from the anterior vaginal fornix area. The vagina of the CG group had
      a stratified squamous epithelium with a moderate degree of cellular infiltration
      with lymphocytes and plasma cells in the lamina propia. Treated ewes (ISR and AR)
      had epithelial hyperplasia and hypertrophy. ISR ewes had haemorrhage and
      perivascular infiltrate and an increased number of epithelial cells, neutrophils,
      macrophages and erythrocytes at IS removal. The use of IS generated histological
      and cytological alterations in the vaginal wall when used for oestrous
      synchronization in anoestrous ewes.

PMID- 25604996
TI  - Transcriptome and histopathological changes in mouse brain infected with Neospora
      caninum.
AB  - Neospora caninum is a protozoan parasite that causes neurological disorders in
      dogs and cattle. It can cause nonsuppurative meningoencephalitis and a variety of
      neuronal symptoms are observed, particularly in dogs. However, the pathogenic
      mechanism, including the relationship between the parasite distribution and the
      clinical signs, is unclear. In this study, to understand the pathogenic mechanism
      of neosporosis, parasite distribution and lesions were assessed in the brain of
      mice infected with N. caninum (strain Nc-1). Host gene expression was also
      analyzed with RNA sequencing (RNA-Seq). The histopathological lesions in the
      frontal lobe and the medulla oblongata were significantly more severe in
      symptomatic mice than in asymptomatic mice, although no association between the
      severity of the lesions and parasite numbers was found. In infected mice, the
      expression of 772 mouse brain genes was upregulated. A GOstat analysis predicted
      that the upregulated genes were involved in the host immune response. Genes whose
      expression correlated positively and negatively with parasite numbers were
      involved in the host immune response, and neuronal morphogenesis and lipid
      metabolic processes, respectively. These results suggest that changes in the gene
      expression profile associated with neuronal functions as well as immune responses
      can contribute to the pathogenesis in N. caninum-infected animals. 

PMID- 25604997
TI  - Colonization of malaria vectors under semi-field conditions as a strategy for
      maintaining genetic and phenotypic similarity with wild populations.
AB  - BACKGROUND: Malaria still accounts for an estimated 207 million cases and 627,000
      deaths worldwide each year. One proposed approach to complement existing malaria
      control methods is the release of genetically-modified (GM) and/or sterile male
      mosquitoes. As opposed to laboratory colonization, this requires realistic semi
      field systems to produce males that can compete for females in nature. This study
      investigated whether the establishment of a colony of the vector Anopheles
      arabiensis under more natural semi-field conditions can maintain higher levels of
      genetic diversity than achieved by laboratory colonization using traditional
      methods. METHODS: Wild females of the African malaria vector An. arabiensis were
      collected from a village in southern Tanzania and used to establish new colonies
      under different conditions at the Ifakara Health Institute. Levels of genetic
      diversity and inbreeding were monitored in colonies of An. arabiensis that were
      simultaneously established in small cage colonies in the SFS and in a large semi
      field (SFS) cage and compared with that observed in the original founder
      population. Phenotypic traits that determine their fitness (body size and
      energetic reserves) were measured at 10(th) generation and compared to founder
      wild population. RESULTS: In contrast to small cage colonies, the SFS population
      of An. arabiensis exhibited a higher degree of similarity to the founding field
      population through time in several ways: (i) the SFS colony maintained a
      significantly higher level of genetic variation than small cage colonies, (ii)
      the SFS colony had a lower degree of inbreeding than small cage colonies, and
      (iii) the mean and range of mosquito body size in the SFS colony was closer to
      that of the founding wild population than that of small cage colonies. Small cage
      colonies had significantly lower lipids and higher glycogen abundances than SFS
      and wild population. CONCLUSIONS: Colonization of An. arabiensis under semi-field
      conditions was associated with the retention of a higher degree of genetic
      diversity, reduced inbreeding and greater phenotypic similarity to the founding
      wild population than observed in small cage colonies. Thus, mosquitoes from such
      semi-field populations are expected to provide more realistic representation of
      mosquito ecology and physiology than those from small cage colonies.

PMID- 25604998
TI  - A copper(I)-arene complex with an unsupported eta6 interaction.
AB  - Addition of PR3 (R=Ph or OPh) to [Cu(eta(2)-Me6C6)2][PF6] results in the
      formation of [(eta(6)-Me6C6)Cu(PR3)][PF6], the first copper-arene complexes to
      feature an unsupported eta(6) arene interaction. A DFT analysis reveals that the
      preference for the eta(6) binding mode is enforced by the steric clash between
      the methyl groups of the arene ligand and the phenyl rings of the phosphine co
      ligand.

PMID- 25604999
TI  - Ligation-assisted endoscopic enucleation for the treatment of colorectal
      submucosal tumours originating in the muscularis propria.
AB  - AIM: A ligation-assisted endoscopic enucleation (EE-L) technique was developed
      and was evaluated to determine its efficacy and safety for treating colorectal
      submucosal tumours (< 10 mm) originating in the muscularis propria. METHOD: EE-L
      was used to treat 13 patients between January 2011 and January 2014. The tumour
      was sucked into a transparent cap and ligated at its base by a rubber band
      ligature attached to the tip of the endoscope. With the creation of a pseudo
      stalk, the tumour was then enucleated using endoscopic dissection and the wound
      was closed with clips. RESULTS: All tumours [median diameter 6.8 (4-10) mm] were
      successfully enucleated [procedure time 19 (11-27) min]. Histopathological
      examination identified 11 (84.6%) to be leiomyoma and 2 (15.4%) low-risk
      gastrointestinal stromal tumours. No perforations or massive haemorrhage occurred
      and there were no recurrences during a follow-up of 3-39 months. CONCLUSION: EE-L
      is a successful technique for the removal of small colorectal tumours in the
      muscularis propria with few complications and enables a histopathological
      diagnosis. In this study, all the resected lesions had a benign pathology.

PMID- 25605000
TI  - Size-controllable synthesis of bare gold nanoparticles by femtosecond laser
      fragmentation in water.
AB  - We report a size-controllable synthesis of stable aqueous solutions of ultrapure
      low-size-dispersed Au nanoparticles by methods of femtosecond laser fragmentation
      from preliminary formed colloids. Such approach makes possible the tuning of mean
      nanoparticle size between a few nm and several tens of nm under the size
      dispersion lower than 70% by varying the fluence of pumping radiation during the
      fragmentation procedure. The efficient size control is explained by 3D geometry
      of laser fragmentation by femtosecond laser-induced white light super-continuum
      and plasma-related phenomena. Despite the absence of any protective ligands, the
      nanoparticle solutions demonstrate exceptional stability due to electric
      repulsion effect associated with strong negative charging of formed
      nanoparticles. Stable aqueous solutions of bare gold nanoparticles present a
      unique object with a variety of potential applications in catalysis, surface
      enhanced Raman spectroscopy, photovoltaics, biosensing and biomedicine. 

PMID- 25605001
TI  - Pliable natural biocide: Jaburetox is an intrinsically disordered insecticidal
      and fungicidal polypeptide derived from jack bean urease.
AB  - Jaburetox is a polypeptide derived from jack bean (Canavalia ensiformis) urease
      and toxic to a broad spectrum of insects, phytopathogenic filamentous fungi and
      yeasts of medical importance. The elucidation of the structural basis for the
      mode of action of Jaburetox is the focus of this multifaceted study. Jaburetox in
      solution is a monomer of 11.0 kDa featuring a large hydrodynamic radius,
      suggestive of a disordered polypeptide. The intrinsically disordered nature of
      Jaburetox was theoretically predicted by a comprehensive bioinformatics analysis
      and experimentally confirmed by light scattering as well as by circular dichroism
      and NMR spectroscopy. NMR signal assignment provided backbone secondary chemical
      shifts that indicated that Jaburetox has a low propensity to assume a stable
      secondary structure. (15)N relaxation studies revealed significant backbone
      mobility, especially in the N-terminal portion of the polypeptide. The solution
      structure of Jaburetox shows the presence of an alpha-helical motif close to the
      N terminus, together with two turn-like structures situated in the central
      portion of the protein and close to the C terminus. Similar regions were
      predicted as potential protein-protein interaction sites using computational
      tools. The knowledge of the structural properties of Jaburetox in solution is a
      key step to correlate its structural and biological activities.

PMID- 25605002
TI  - The ubiquity of alpine plant radiations: from the Andes to the Hengduan
      Mountains.
AB  - Alpine plant radiations are compared across the world's major mountain ranges and
      shown to be overwhelmingly young and fast, largely confined to the Pliocene and
      Pleistocene, and some of them apparently in the early explosive phase of
      radiation. Accelerated diversification triggered by island-like ecological
      opportunities following the final phases of mountain uplift, and in many cases
      enabled by the key adaptation of perennial habit, provides a general model for
      alpine plant radiations. Accelerated growth form evolution facilitated by
      perenniality provides compelling evidence of ecological release and suggests
      striking parallels between island-like alpine, and especially tropicalpine
      radiations, and island radiations more generally. These parallels suggest that
      the world's mountains offer an excellent comparative system for explaining
      evolutionary radiation.

PMID- 25605003
TI  - Newly identified antiatherosclerotic activity of methotrexate and adalimumab:
      complementary effects on lipoprotein function and macrophage cholesterol
      metabolism.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with accelerated
      atherosclerosis. The reduction in cardiovascular risk that is induced by
      methotrexate (MTX) and anti-tumor necrosis factor alpha agents in RA is
      considered secondary to their anti-inflammatory action, but their effects on
      serum lipoprotein function and foam cell formation are unknown. The reduced
      capacity of high-density lipoprotein (HDL) to promote cell cholesterol efflux and
      the increased serum cell cholesterol-loading capacity (CLC) demonstrated in RA
      may contribute to foam cell development. The aim of this study was to investigate
      the influence of MTX and adalimumab treatment on serum cholesterol efflux
      capacity (CEC) and CLC in RA patients and to study the in vitro effects of the
      two drugs on macrophage cholesterol handling. METHODS: Sera from RA patients
      treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before
      treatment, after 6 weeks of treatment, and after 6 months of treatment were
      analyzed for CEC and CLC by radioisotopic and fluorometric techniques,
      respectively. The influence of MTX and adalimumab on macrophage cholesterol
      efflux and uptake was evaluated in vitro using human THP-1-derived macrophages.
      RESULTS: MTX treatment was associated with increases in serum HDL, low-density
      lipoprotein, and total cholesterol levels and with ATP-binding cassette G1
      mediated and scavenger receptor class B type I (SR-BI)-mediated increases in CEC;
      MTX treatment was not associated with modifications in CLC. Adalimumab treatment
      was associated with increases in serum HDL levels, a transient increase in SR-BI
      mediated CEC, a transient decrease in ATP-binding cassette A1-mediated CEC, and a
      significant reduction in CLC; in addition, adalimumab reduced macrophage
      cholesterol uptake in vitro. CONCLUSION: Antiatherosclerotic activity associated
      with MTX and adalimumab may be mediated by beneficial and complementary effects
      on lipoprotein functions and on macrophage cholesterol handling. As a whole,
      these mechanisms may oppose foam cell formation.

PMID- 25605004
TI  - Predation by signal crayfish Pacifastacus leniusculus on fish eggs and its
      consequences for coregonid recruitment.
AB  - The character and magnitude of predation by the invasive, ectothermic
      Pacifastacus leniusculus, a crayfish widely introduced to Europe and Japan from
      North America, on the eggs of coregonid fishes, vendace Coregonus albula and
      whitefish Coregonus lavaretus were examined by experimentation, modelling and
      field data. The present results showed that P. leniusculus has the potential to
      be very efficient predator of fish eggs under winter conditions, but the
      predation by P. leniusculus did not significantly decrease production of
      coregonid larvae during the years with a high P. leniusculus population in the
      study lake. Hence, the mortality caused by the novel invertebrate predator
      appeared to compensate for other yet unexplored mortality factors instead of
      having an additive effect on the present salmonids.

PMID- 25605005
TI  - Predictive value of plasma neutrophil gelatinase-associated lipocalin for acute
      kidney injury in intensive care unit patients after major non-cardiac surgery.
AB  - AIM: The performance of plasma neutrophil gelatinase-associated lipocalin (pNGAL)
      for prediction of acute kidney injury (AKI) in non-cardiac surgical patients has
      not been well described. This study investigates the use of pNGAL for early
      detection of AKI in patients admitted to an intensive care unit (ICU) after major
      or ultra-major non-cardiac surgery. METHODS: A total of 151 patients were
      recruited. Blood samples at 0 h and 6 h post-ICU admission were collected.
      Primary outcome was occurrence of AKI within 48 h of ICU admission defined using
      Acute Kidney Injury Network (AKIN) classification. RESULTS: Forty-five (29.8%)
      patients developed AKI within 48 h of ICU admission. Among them, 22, 14, and nine
      were classified as AKIN Stage 1, 2, and 3 respectively. pNGAL levels at 0 h and 6
      h were significantly related to AKI severity. The AUROC for pNGAL at 0 h and 6 h
      increased with AKI severity (AKIN stage >=1 0.671 +/- 0.048 and 0.691 +/- 0.047;
      stage >=2 0.737 +/- 0.055 and 0.796 +/- 0.048; stage 3 0.829 +/- 0.072 and 0.860
      +/- 0.065, respectively) and requirement of renal replacement therapy (0.880 +/-
      0.059 & 0.837 +/- 0.088). Change of pNGAL from 0 h to 6 h showed no advantage in
      predictive power compared with pNGAL level at 0 h or 6 h alone. The addition of
      pNGAL into clinical AKI prediction model could only provide marginal benefit.
      CONCLUSION: pNGAL correlated with severity of AKI and requirement of renal
      replacement therapy in ICU patients who received major or ultra-major non-cardiac
      surgery. However, the benefit of adding pNGAL into clinical AKI prediction model
      is marginal.

PMID- 25605006
TI  - Proteins interacting with mitochondrial ATP-dependent Lon protease (MAP1) in
      Magnaporthe oryzae are involved in rice blast disease.
AB  - The ATP-dependent Lon protease is involved in many physiological processes. In
      bacteria, Lon regulates pathogenesis and, in yeast, Lon protects mitochondia from
      oxidative damage. However, little is known about Lon in fungal phytopathogens.
      MAP1, a homologue of Lon in Magnaporthe oryzae, was recently identified to be
      important for stress resistance and pathogenesis. Here, we focus on a novel
      pathogenic pathway mediated by MAP1. Based on an interaction system between rice
      and a tandem affinity purification (TAP)-tagged MAP1 complementation strain, we
      identified 23 novel fungal proteins from infected leaves using a TAP approach
      with mass spectrometry, and confirmed that 14 of these proteins physically
      interact with MAP1 in vivo. Among these 14 proteins, 11 candidates, presumably
      localized to the mitochondria, were biochemically determined to be substrates of
      MAP1 hydrolysis. Deletion mutants were created and functionally analysed to
      further confirm the involvement of these proteins in pathogenesis. The results
      indicated that all mutants showed reduced conidiation and sensitivity to hydrogen
      peroxide. Appressorial formations were not affected, although conidia from
      certain mutants were morphologically altered. In addition, virulence was reduced
      in four mutants, enhanced (with lesions forming earlier) in two mutants and
      remained unchanged in one mutant. Together with the known virulence-related
      proteins alternative oxidase and enoyl-CoA hydratase, we propose that most of the
      Lon-interacting proteins are involved in the pathogenic regulation pathway
      mediated by MAP1 in M. oryzae. Perturbation of this pathway may represent an
      effective approach for the inhibition of rice blast disease.

PMID- 25605007
TI  - Enhanced high-frequency molecular dynamics in the near-surface region of
      polystyrene thin films observed with beta-NMR.
AB  - beta-detected nuclear spin relaxation of (8)Li(+) has been used to probe the
      depth dependence of molecular dynamics in high- and low-molecular-weight
      deuterated polystyrene. The average nuclear spin-lattice relaxation rate,
      1/T(avg)(1), is a measure of the spectral density of the polymer motion at the
      Larmor frequency (41 MHz at 6.55 T). In both samples, 1/T(avg)(1) is depth
      independent below ~200 K but above this temperature it decreases approximately
      exponentially with distance from the free surface, returning to bulk behavior for
      depths greater than ~10 nm. This is direct evidence for a region near the free
      surface with enhanced molecular dynamics compared with the bulk. The effective
      thickness of the surface region increases with increasing temperature and is
      finite even above the glass transition. These results present challenges for the
      current understanding of dynamics near the surface of polymer glasses.

PMID- 25605008
TI  - Metformin inhibits tumor growth by regulating multiple miRNAs in human
      cholangiocarcinoma.
AB  - The antidiabetic drug metformin exerts antineoplastic effects in many types of
      malignancies, however the effect of metformin on cholangiocarcinoma (CCA) still
      remains unclear. In the present study, we investigated that metformin treatment
      was closely associated with the clinicopathologic characteristics and improved
      postoperative survival of CCA patients. Metformin inhibited CCA tumor growth by
      cell cycle arrest in vitro and in vivo. We explored that the expression of six
      miRNAs (mir124, 182, 27b, let7b, 221 and 181a), which could directly target cell
      cycle-regulatory genes, was altered by metformin in vitro and in vivo. These
      miRNAs were dysregulated in cholangiocarcinoma and promoted the CCA genesis and
      metformin exactly modulated these carcinogenic miRNAs expression to arrest the
      cell cycle and inhibit the proliferation. Meanwhile, these miRNAs expression
      changes correlated with the tumor volume and postoperative survival of CCA
      patients and could be used to predict the prognosis. Further we confirmed that
      metformin upregulated Drosha to modulate these miRNAs expression. Our results
      elucidated that metformin inhibited CCA tumor growth via the regulation of Drosha
      mediated multiple carcinogenic miRNAs expression and comprehensive evaluation of
      these miRNAs expression could be more efficient to predict the prognosis.
      Moreover, metformin might be a quite promising strategy for CCA prevention and
      treatment. 

PMID- 25605009
TI  - Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis.
AB  - Dietary consumption of genistein, found in soy, has been associated with a
      potentially protective role in colorectal cancer (CRC) development and
      progression. Herein we demonstrate that genistein will inhibit human CRC cell
      invasion and migration, that it does so at non-cytotoxic concentrations and we
      demonstrate this in multiple human CRC cell lines. After orthotopic implantation
      of human CRC tumors into mice, oral genistein did not inhibit tumor growth, but
      did inhibit distant metastasis formation, and was non-toxic to mice. Using a qPCR
      array, we screened for genistein-induced changes in gene expression, followed by
      Western blot confirmation, demonstrating that genistein downregulated matrix
      metalloproteinase 2 and Fms-Related Tyrosine Kinase 4 (FLT4; vascular endothelial
      growth factor receptor 3). After demonstrating that genistein suppressed neo
      angiogenesis in mouse tumors, we examined FLT4 expression in primary CRC and
      adjacent normal colonic tissue from 60 human subjects, demonstrating that
      increased FLT4 significantly correlates with increased stage and decreased
      survival. In summary, we demonstrate for the first time that genistein inhibits
      human CRC metastasis at dietary, non-toxic, doses. FLT4 is identified as a marker
      of metastatic disease, and as a response marker for small molecule therapeutics
      that inhibit CRC metastasis. 

PMID- 25605011
TI  - Long-term treatment with imatinib results in profound mast cell deficiency in Ph+
      chronic myeloid leukemia.
AB  - Although mast cells (MC) play an important role in allergic reactions, their
      physiologic role remains unknown. In mice, several models of MC-deficiency have
      been developed. However, no comparable human model is available. We examined the
      in vitro- and in vivo effects of the KIT-targeting drug imatinib on growth and
      development of human MC. Imatinib was found to inhibit stem cell factor (SCF)
      induced differentiation of MC in long-term suspension cultures (IC50: 0.01 uM).
      Correspondingly, long-term treatment of chronic myeloid leukemia (CML) patients
      with imatinib (400 mg/day) resulted in a marked decrease in MC. In patients with
      continuous complete molecular response during therapy, bone marrow MC decreased
      to less than 5% of pre-treatment values, and also serum tryptase concentrations
      decreased significantly (pre-treatment: 32.0 +/- 11.1 ng/ml; post-therapy: 3.4 +/
      1.8, p<0.01). Other myeloid lineages, known to develop independently of KIT,
      were not affected by imatinib-therapy. Imatinib also produced a substantial
      decrease in MC-development in mice. However, no clinical syndrome attributable to
      drug-induced MC-deficiency was recorded in our CML patients. Together, imatinib
      suppresses MC production in vitro and in vivo. However, drug-induced MC depletion
      is not accompanied by adverse clinical events, suggesting that MC are less
      relevant to homeostasis in healthy tissues than we assumed so far.

PMID- 25605010
TI  - Lovastatin enhances adenovirus-mediated TRAIL induced apoptosis by depleting
      cholesterol of lipid rafts and affecting CAR and death receptor expression of
      prostate cancer cells.
AB  - Oncolytic adenovirus and apoptosis inducer TRAIL are promising cancer therapies.
      Their antitumor efficacy, when used as single agents, is limited. Oncolytic
      adenoviruses have low infection activity, and cancer cells develop resistance to
      TRAIL-induced apoptosis. Here, we explored combining prostate-restricted
      replication competent adenovirus-mediated TRAIL (PRRA-TRAIL) with lovastatin, a
      commonly used cholesterol-lowering drug, as a potential therapy for advanced
      prostate cancer (PCa). Lovastatin significantly enhanced the efficacy of PRRA
      TRAIL by promoting the in vivo tumor suppression, and the in vitro cell killing
      and apoptosis induction, via integration of multiple molecular mechanisms.
      Lovastatin enhanced PRRA replication and virus-delivered transgene expression by
      increasing the expression levels of CAR and integrins, which are critical for
      adenovirus 5 binding and internalization. Lovastatin enhanced TRAIL-induced
      apoptosis by increasing death receptor DR4 expression. These multiple effects of
      lovastatin on CAR, integrins and DR4 expression were closely associated with
      cholesterol-depletion in lipid rafts. These studies, for the first time, show
      correlations between cholesterol/lipid rafts, oncolytic adenovirus infection
      efficiency and the antitumor efficacy of TRAIL at the cellular level. This work
      enhances our understanding of the molecular mechanisms that support use of
      lovastatin, in combination with PRRA-TRAIL, as a candidate strategy to treat
      human refractory prostate cancer in the future. 

PMID- 25605012
TI  - Molecular chaperone GRP78 enhances aggresome delivery to autophagosomes to
      promote drug resistance in multiple myeloma.
AB  - Despite the clinical benefit of the proteasome inhibitor bortezomib, multiple
      myeloma (MM) patients invariably relapse through poorly defined mechanisms.
      Myeloma cells inevitably develop chemoresistance that leads to disease relapse
      and patient-related deaths. Studies in tumor cell lines and biopsies obtained
      from patients refractory to therapy have revealed that myeloma cells adapt to
      stress by inducing expression of glucose-regulated protein 78 (GRP78), an
      endoplasmic reticulum (ER) chaperone with anti-apoptotic properties. Treatment of
      myeloma cells with bortezomib increased GRP78 levels and activated GRP78
      dependent autophagy. Expression profiling indicated that GRP78-encoding HSPA5 was
      significantly upregulated in bortezomib-resistant cells. Co-treatment with the
      anti-diabetic agent metformin suppressed GRP78 and enhanced the anti
      proliferative effect of bortezomib. Bortezomib treatment led to GRP78 co
      localization with proteotoxic protein aggregates, known as aggresomes.
      Pharmacologic suppression, genetic ablation or mutational inactivation of GRP78
      followed by bortezomib treatment led to the accumulation of aggresomes but
      impaired autophagy and enhanced anti-myeloma effect of bortezomib. GRP78 was co
      immunoprecipitated with the KDEL receptor, an ER quality control regulator that
      binds proteins bearing the KDEL motif to mediate their retrieval from the Golgi
      complex back to the ER. Taken together, we demonstrate that inhibition of GRP78
      functional activity disrupts autophagy and enhances the anti-myeloma effect of
      bortezomib. 

PMID- 25605013
TI  - Galectin-1 is overexpressed in CD133+ human lung adenocarcinoma cells and
      promotes their growth and invasiveness.
AB  - Previous studies demonstrated that a subpopulation of cancer cells, which are
      CD133 positive (CD133+) feature higher invasive and metastatic abilities, are
      called cancer stem cells (CSCs). By using tumor cells derived from patients with
      lung adenocarcinoma, we found that galectin-1 is highly overexpressed in the
      CD133+ cancer cells as compared to the normal cancer cells (CD133-) from the same
      patients. We overexpressed galectin-1 in CD133- cancer cells and downregulated it
      in CSCs. We found that overexpression of galectin-1 promoted invasiveness of
      CD133- cells, while knockdown of galectin-1 suppressed proliferation, colony
      formation and invasiveness of CSCs. Furthermore, tumor growth was significantly
      inhibited in CSCs xenografts with knockdown of galectin-1 as compared to CSCs
      treated with scramble siRNAs. Biochemical studies revealed that galectin-1
      knockdown led to the suppression of COX-2/PGE2 and AKT/mTOR pathways, indicating
      galectin-1 might control the phenotypes of CSCs by regulating these signaling
      pathways. Finally, a retrospective study revealed that galectin-1 levels in blood
      circulation negatively correlates with overall survival and positively correlates
      with lymph node metastasis of the patients. Taken together, these findings
      suggested that galectin-1 plays a major role on the tumorigenesis and
      invasiveness of CD133+ cancer cells and might serve as a potential therapeutic
      target for treatment of human patients with lung adenocarcinoma. 

PMID- 25605015
TI  - Aberrant expression of the embryonic transcription factor brachyury in human
      tumors detected with a novel rabbit monoclonal antibody.
AB  - The embryonic transcription factor brachyury is overexpressed in a variety of
      human tumors, including lung, breast, colon and prostate carcinomas, chordomas
      and hemangioblastomas. In human carcinoma cells, overexpression of brachyury
      associates with the occurrence of the phenomenon of epithelial-mesenchymal
      transition (EMT), acquisition of metastatic propensity and resistance to a
      variety of anti-cancer therapeutics. Brachyury is preferentially expressed in
      human tumors vs. normal adult tissues, and high levels of this molecule associate
      with poor prognosis in patients with lung, colon and prostate carcinomas, and in
      breast cancer patients treated with adjuvant tamoxifen. Brachyury is immunogenic
      in humans and vaccines against this novel oncotarget are currently undergoing
      clinical investigation. While our group and others have employed various anti
      brachyury antibodies to interrogate the above findings, we report here on the
      development and thorough characterization of a novel rabbit monoclonal antibody
      (MAb 54-1) that reacts with distinct high affinity and specificity with human
      brachyury. MAb 54-1 was successfully used in ELISA, western blot,
      immunofluorescence and immunohistochemistry assays to evaluate expression of
      brachyury in various human tumor cell lines and tissues. We propose the use of
      this antibody to assist in research studies of EMT and in prognostic studies for
      a range of human tumors. 

PMID- 25605014
TI  - Top2a identifies and provides epigenetic rationale for novel combination
      therapeutic strategies for aggressive prostate cancer.
AB  - Progression of aggressive prostate cancers (PCa) with androgen receptor splice
      variants or neuroendrocrine features is currently untreatable in the clinic.
      Therefore novel therapies are urgently required. We conducted RNA-seq using
      tumors from a unique murine transplant mouse model which spontaneously progresses
      to metastatic disease. Differential gene expression analysis revealed a
      significant increase of topoisomerase IIalpha, Top2a (Top2a) in metastatic
      tumors. Interrogation of human data revealed that increased Top2a expression in
      primary tumors selected patients with more aggressive disease. Further,
      significant positive correlation was observed between Top2a and the histone
      methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2
      inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine
      and human prostate cancer cell lines. Additionally, combination therapy extended
      time to progression and increased therapeutic efficacy in vivo. Overall, our
      studies demonstrate that patients screened for Top2a and Ezh2 expression would
      exhibit significant response to a combinational treatment involving low dose
      etoposide combined with Ezh2 inhibition. In addition, our data suggests that this
      combination therapeutic strategy is beneficial against aggressive PCa, and
      provides strong rationale for continued clinical development. 

PMID- 25605016
TI  - Upregulation of miR-328 and inhibition of CREB-DNA-binding activity are critical
      for resveratrol-mediated suppression of matrix metalloproteinase-2 and subsequent
      metastatic ability in human osteosarcomas.
AB  - Osteosarcomas, the most common malignant bone tumors, show a potent capacity for
      local invasion and pulmonary metastasis. Resveratrol (RESV), a phytochemical,
      exhibits multiple tumor-suppressing activities and has been tested in clinical
      trials. However, the antitumor activities of RESV in osteosarcomas are not yet
      completely defined. In osteosarcoma cells, we found that RESV inhibited the
      migration/invasion in vitro and lung metastasis in vivo by suppressing matrix
      metalloproteinase (MMP)-2. We identified that RESV exhibited a transcriptional
      inhibitory effect on MMP-2 through reducing CREB-DNA-binding activity. Moreover,
      a microRNA (miR) analysis showed that miR-328 was predominantly upregulated after
      RESV treatment. Inhibition of miR-328 significantly relieved MMP-2 and motility
      suppression imposed by RESV treatment. Furthermore, ectopic miR-328 expression in
      highly invasive cells decreased MMP-2 expression and invasive abilities.
      Mechanistic investigations found that JNK and p38 MAPK signaling pathways were
      involved in RESV-regulated CREB-DNA-binding activity, miR328 expression, and cell
      motility. Clinical samples indicated inverse expression between MMP-2 and miR-328
      in normal bone and osteosarcoma tissues. The inverse correlation of MMP-2 and miR
      328 was also observed in tumor specimens, and MMP-2 expression was linked to
      tumor metastasis. Taken together, our results provide new insights into the role
      of RESV-induced molecular and epigenetic regulation in suppressing tumor
      metastasis. 

PMID- 25605017
TI  - Reduction of miR-29c enhances pancreatic cancer cell migration and stem cell-like
      phenotype.
AB  - The hallmarks of pancreatic cancer are limitless replicative potential as well as
      tissue invasion and metastasis, leading to an extremely aggressive disease with
      shockingly high lethality. However, the molecular mechanisms underlying these
      characteristics remain largely unclear. Herein, we report the results of a
      differential miRNA expression screen that compared pancreatic cancer tissues and
      normal pancreatic tissues, where the pancreatic cancer tissues had highly
      downregulated miR-29c with relative Wnt cascade hyperactivation. MiR-29c directly
      suppressed the following Wnt upstream regulators: frequently rearranged in
      advanced T-cell lymphomas 2 (FRAT2), low-density lipoprotein receptor-related
      protein 6 (LRP6), Frizzled-4 (FZD4) and Frizzled-5 (FZD5). Furthermore,
      transforming growth factor-beta (TGF-beta) inhibited miR-29c expression, leading
      to Wnt activation. Significantly, our results were consistent with an important
      correlation between miR-29c levels and TGF-beta hyperactivation and the activated
      Wnt cascade in human pancreatic cancer specimens. These findings reveal a novel
      mechanism for Wnt hyperactivation in pancreatic cancer and may suggest a new
      target for clinical intervention in pancreatic cancer. 

PMID- 25605018
TI  - Folate-mediated mitochondrial targeting with doxorubicin-polyrotaxane
      nanoparticles overcomes multidrug resistance.
AB  - Resistance to treatment with anticancer drugs is a signii!?cant obstacle and a
      fundamental cause of therapeutic failure in cancer therapy. Functional
      doxorubicin (DOX) nanoparticles for targeted delivery of the classical cytotoxic
      anticancer drug DOX to tumor cells, using folate-terminated polyrotaxanes along
      with dequalinium, have been developed and proven to overcome this resistance due
      to specific molecular features, including a size of approximately 101 nm, a zeta
      potential of 3.25 mV and drug-loading content of 18%. Compared with free DOX, DOX
      hydrochloride, DOX nanoparticles, and targeted DOX nanoparticles, the functional
      DOX nanoparticles exhibited the strongest anticancer efi!?cacy in vitro and in
      the drug-resistant MCF-7/Adr (DOX) xenograft tumor model. More specifically, the
      nanoparticles signii!?cantly increased the intracellular uptake of DOX,
      selectively accumulating in mitochondria and the endoplasmic reticulum after
      treatment, with release of cytochrome C as a result. Furthermore, the caspase-9
      and caspase-3 cascade was activated by the functional DOX nanoparticles through
      upregulation of the pro-apoptotic proteins Bax and Bid and suppression of the
      antiapoptotic protein Bcl-2, thereby enhancing apoptosis by acting on the
      mitochondrial signaling pathways. In conclusion, functional DOX nanoparticles may
      provide a strategy for increasing the solubility of DOX and overcoming multidrug
      resistant cancers. 

PMID- 25605019
TI  - RMP predicts survival and adjuvant TACE response in hepatocellular carcinoma.
AB  - Adjuvant transcatheter arterial chemoembolization (TACE) protects against
      hepatocellular carcinoma (HCC) and is associated with reduced disease recurrence
      and improved outcome after surgery. However, deterioration of liver function
      after TACE negatively impacts the patient prognosis and limits it use as an
      option to prolong survival. We analyzed two independent cohorts that included a
      total of 510 patients with HCC who had undergone tumor resection.
      Immunohistochemistry assay was used to measure RPB5-mediating protein (RMP)
      expression and assessed their association with recurrence rate and response to
      therapy with adjuvant TACE. In patients with HCC, the expression of RMP in tumor
      is associated with age, gender, tumor size, portal venous invasion, TNM stages,
      BCLC stages and overall survival. Among patients with high RMP expression,
      adjuvant TACE after resection was associated with early recurrence. Even in the
      patients with small tumor size (no more than 5 cm) or no venous invasion, RMP
      status is associated with response to adjuvant TACE. RMP status in tumors may be
      a useful marker in estimating prognosis in patients with HCC and in assisting in
      the selection of patients who are likely to benefit from adjuvant TACE to prevent
      relapse. 

PMID- 25605021
TI  - TXNIP interaction with the Her-1/2 pathway contributes to overall survival in
      breast cancer.
AB  - Previous studies have indicated that Her-2 induction causes a strong decrease in
      thioredoxin interaction protein (TXNIP) in breast cancer cells. However, little
      is known regarding the prognostic value of TXNIP in clinical breast cancer
      patients with anti-Her-2 treatment. Using a tissue microarray, we detected TXNIP
      and p27 expression in breast cancer tissue, as well as corresponding noncancerous
      tissues. We found that TXNIP expression was associated with better overall
      survival (OS) in these 150 breast cancer patients and that TXNIP and Her-2
      expression status were significantly inversely correlated (r=-0.334, P<0.001).
      These results were validated in another 101 breast cancer tissue samples (r=
      0.422, P<0.001). Moreover, TXNIP expression increased significantly following
      treatment of the human breast cancer cell lines BT474 and SK-BR-3 with a Her-1/2
      inhibitor. Furthermore, TXNIP transfection induced p27 expression and G1 cell
      cycle arrest and apoptosis. Taken together, our findings suggest that TXNIP plays
      a critical role in anti-Her-1/Her-2 treatment and may be a potential prognostic
      marker in breast cancer. 

PMID- 25605020
TI  - Adhesion glycoprotein CD44 functions as an upstream regulator of a network
      connecting ERK, AKT and Hippo-YAP pathways in cancer progression.
AB  - Targeted therapies are considered to be the future of cancer treatment. However,
      the mechanism through which intracellular signaling pathways coordinate to
      modulate oncogenesis remains to be elucidated. In this study, we describe a novel
      crosstalk among ERK, AKT and Hippo-YAP pathways, with CD44 as an upstream
      regulator. High cell density leads to activation of ERK and AKT but inactivation
      of YAP in cancer cells. CD44 modulates cell proliferation and cell cycle but not
      apoptosis. The expression and activity of cell cycle genes were cooperatively
      regulated by ERK, AKT and Hippo-YAP signaling pathways through CD44-mediated
      mechanisms. In addition, CD44 depletion abrogates cancer stem cell properties of
      tumor initiating cells. Taken together, we described a paradigm where CD44
      functions as an upstream regulator sensing the extracellular environment to
      modulate ERK, AKT and Hippo-YAP pathways which cooperatively control downstream
      gene expression to modulate cell contact inhibition of proliferation, cell cycle
      progression and maintenance of tumor initiating cells. Our current study provides
      valuable information to design targeted therapeutic strategies in cancers. 

PMID- 25605022
TI  - p53 activates G1 checkpoint following DNA damage by doxorubicin during transient
      mitotic arrest.
AB  - Recovery from DNA damage is critical for cell survival. The serious damage is not
      able to be repaired during checkpoint and finally induces cell death to prevent
      abnormal cell growth. In this study, we demonstrated that 8N-DNA contents are
      accumulated via re-replication during prolonged recovery period containing
      serious DNA damage in mitotic cells. During the incubation for recovery, a
      mitotic delay and initiation of an abnormal interphase without cytokinesis were
      detected. Whereas a failure of cytokinesis occurred in cells with no relation
      with p53/p21, re-replication is an anomalous phenomenon in the mitotic DNA damage
      response in p53/p21 negative cells. Cells with wild-type p53 are accumulated just
      prior to the initiation of DNA replication through a G1 checkpoint after mitotic
      DNA damage, even though p53 does not interrupt pre-RC assembly. Finally, these
      cells undergo cell death by apoptosis. These data suggest that p53 activates G1
      checkpoint in response to mitotic DNA damage. Without p53, cells with mitotic DNA
      damage undergo re-replication leading to accumulation of damage.

PMID- 25605024
TI  - Printing in three dimensions with graphene.
AB  - Responsive graphene oxide sheets form non-covalent networks with optimum
      rheological properties for 3D printing. These networks have shear thinning
      behavior and sufficiently high elastic shear modulus (G') to build self
      supporting 3D structures by direct write assembly. Drying and thermal reduction
      leads to ultra-light graphene-only structures with restored conductivity and
      elastomeric behavior. 

PMID- 25605023
TI  - HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome
      chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma.
AB  - Gain-of-function mutations in the catalytic site of EZH2 (Enhancer of Zeste
      Homologue 2), is observed in about 22% of diffuse large B-cell lymphoma (DLBCL)
      cases. Here we show that selective inhibition of histone deacetylase 1,2
      (HDAC1,2) activity using a small molecule inhibitor causes cytotoxic or
      cytostatic effects in EZH2 gain-of-function mutant (EZH2GOF) DLBCL cells. Our
      results show that blocking the activity of HDAC1,2 increases global H3K27ac
      without causing a concomitant global decrease in H3K27me3 levels. Our data shows
      that inhibition of HDAC1,2 is sufficient to decrease H3K27me3 present at DSBs,
      decrease DSB repair and activate the DNA damage response in these cells. In
      addition to increased H3K27me3, we found that the EZH2GOF DLBCL cells overexpress
      another chemotherapy resistance factor - B-lymphoma and BAL-associated protein
      (BBAP). BBAP monoubiquitinates histone H4K91, a residue that is also subjected to
      acetylation. Our results show that selective inhibition of HDAC1,2 increases
      H4K91ac, decreases BBAP-mediated H4K91 monoubiquitination, impairs BBAP-dependent
      DSB repair and sensitizes the refractory EZH2GOF DLBCL cells to treatment with
      doxorubicin, a chemotherapy agent. Hence, selective HDAC1,2 inhibition provides a
      novel DNA repair mechanism-based therapeutic approach as it can overcome both
      EZH2- and BBAP-mediated DSB repair in the EZH2GOF DLBCL cells. 

PMID- 25605025
TI  - Educational inequalities in major depressive and generalized anxiety disorders:
      results from the French national SIP study.
AB  - OBJECTIVES: Social inequalities in mental disorders have been reported; the lower
      the social position, the higher the prevalence of mental disorders. However,
      these inequalities have not always been observed and results may vary according
      to the indicator of social position, mental health outcome and population
      studied. The objective of this study was to examine the association between
      social position (educational level) and two mental disorders (major depressive
      disorder-MDD and general anxiety disorder-GAD), measured using a structured
      diagnostic interview (MINI), and to evaluate the contribution of work status in
      the explanation of this association. METHODS: The study was based on a national
      representative sample of the French general population of 11,777 people including
      8,072 workers. All analyses were done using weighted data. Bivariate Rao-Scott
      Chi-square tests were conducted, and multivariate analysis was performed using
      weighted logistic regression analysis with adjustment for age. RESULTS: The
      prevalences of MDD/GAD and of less educated people were lower in the working
      population than in the non-working population. Educational inequalities were
      observed for MDD and GAD in the general population. Non-working status
      contributed to explain these inequalities by 23-28 % for MDD and by 23-37 % for
      GAD when the less educated group was considered. Non-working status was strongly
      associated with both disorders. CONCLUSION: These results may improve our
      knowledge on educational inequalities in mental health and help to understand the
      discrepancies in the literature. Effort to preserve jobs and facilitate the
      return to employment may help to reduce social inequalities in mental health.

PMID- 25605027
TI  - Integrating toxicogenomics into human health risk assessment: lessons learned
      from the benzo[a]pyrene case study.
AB  - The use of short-term toxicogenomic tests to predict cancer (or other health
      effects) offers considerable advantages relative to traditional toxicity testing
      methods. The advantages include increased throughput, increased mechanistic data,
      and significantly reduced costs. However, precisely how toxicogenomics data can
      be used to support human health risk assessment (RA) is unclear. In a companion
      paper ( Moffat et al. 2014 ), we present a case study evaluating the utility of
      toxicogenomics in the RA of benzo[a]pyrene (BaP), a known human carcinogen. The
      case study is meant as a proof-of-principle exercise using a well-established
      mode of action (MOA) that impacts multiple tissues, which should provide a best
      case example. We found that toxicogenomics provided rich mechanistic data
      applicable to hazard identification, dose-response analysis, and quantitative RA
      of BaP. Based on this work, here we share some useful lessons for both research
      and RA, and outline our perspective on how toxicogenomics can benefit RA in the
      short- and long-term. Specifically, we focus on (1) obtaining biologically
      relevant data that are readily suitable for establishing an MOA for toxicants,
      (2) examining the human relevance of an MOA from animal testing, and (3)
      proposing appropriate quantitative values for RA. We describe our envisioned
      strategy on how toxicogenomics can become a tool in RA, especially when anchored
      to other short-term toxicity tests (apical endpoints) to increase confidence in
      the proposed MOA, and emphasize the need for additional studies on other MOAs to
      define the best practices in the application of toxicogenomics in RA.

PMID- 25605029
TI  - Development of a more efficient process for production of fuel ethanol from
      bamboo.
AB  - A process for production of fuel ethanol from bamboo treated with concentrated
      sulfuric acid has been previously proposed. To improve efficiency of the process,
      we tested saccharification with 70 weight% (wt%) sulfuric acid, acid-sugar
      separation by ion exclusion, addition of nutrients to the ethanol fermentation,
      and bioconversion of xylose to xylitol. A high efficiency of both sugar recovery
      (82.5 %) and acid recovery (97.5 %) was achieved in the saccharification process
      and in the continuous acid-sugar separation using a modified anion exchange
      resin, respectively. Reduction of the amount of mineral salts added to the
      saccharified liquid after acid-sugar separation did not negatively affect
      performance of the continuous ethanol fermentation. The ethanol yield and
      productivity were 93.7 % and 6 g/l h, respectively, at 35  degrees C and pH 4.0.
      And the ethanol yield and productivity were almost the same even at pH 3.5.
      Moreover, the xylose remaining in the fermented mash was efficiently converted to
      xylitol in batch fermentation by Candida tropicalis strain 2.1776. These results
      demonstrate a more efficient process for the production of fuel ethanol from
      bamboo.

PMID- 25605028
TI  - Putative adverse outcome pathways relevant to neurotoxicity.
AB  - The Adverse Outcome Pathway (AOP) framework provides a template that facilitates
      understanding of complex biological systems and the pathways of toxicity that
      result in adverse outcomes (AOs). The AOP starts with an molecular initiating
      event (MIE) in which a chemical interacts with a biological target(s), followed
      by a sequential series of KEs, which are cellular, anatomical, and/or functional
      changes in biological processes, that ultimately result in an AO manifest in
      individual organisms and populations. It has been developed as a tool for a
      knowledge-based safety assessment that relies on understanding mechanisms of
      toxicity, rather than simply observing its adverse outcome. A large number of
      cellular and molecular processes are known to be crucial to proper development
      and function of the central (CNS) and peripheral nervous systems (PNS). However,
      there are relatively few examples of well-documented pathways that include
      causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS.
      As a first step in applying the AOP framework to adverse health outcomes
      associated with exposure to exogenous neurotoxic substances, the EU Reference
      Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop
      (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and
      developmental neurotoxic outcomes. Although the AOPs outlined during the workshop
      are not fully described, they could serve as a basis for further, more detailed
      AOP development and evaluation that could be useful to support human health risk
      assessment in a variety of ways.

PMID- 25605030
TI  - Acidic pH shock induced overproduction of epsilon-poly-L-lysine in fed-batch
      fermentation by Streptomyces sp. M-Z18 from agro-industrial by-products.
AB  - epsilon-Poly-L-lysine (epsilon-PL) is produced by Streptomyces as a secondary
      metabolite with wide industrial applications, but its production still needs to
      be further enhanced. Environmental stress is an important approach for the
      promotion of secondary metabolites production by Streptomyces. In this study, the
      effect of acidic pH shock on enhancing epsilon-PL production by Streptomyces sp.
      M-Z18 was investigated in a 5-L fermenter. Based on the evaluation of acidic pH
      shock on mycelia metabolic activity and shock parameters optimization, an
      integrated pH-shock strategy was developed as follows: pre-acid-shock adaption at
      pH 5.0 to alleviate the damage caused by the followed pH shock, and then acidic
      pH shock at 3.0 for 12 h (including pH decline from 4.0 to 3.0) to positively
      regulate mycelia metabolic activity, finally restoring pH to 4.0 to provide
      optimal condition for epsilon-PL production. After 192 h of fed-batch
      fermentation, the maximum epsilon-PL production and productivity reached 54.70
      g/L and 6.84 g/L/day, respectively, which were 52.50 % higher than those of
      control without pH shock. These results demonstrated that acidic pH shock is an
      efficient approach for improving epsilon-PL production. The information obtained
      should be useful for epsilon-PL production by other Streptomyces.

PMID- 25605031
TI  - Polymorphism in sulfadimidine/4-aminosalicylic acid cocrystals: solid-state
      characterization and physicochemical properties.
AB  - Polymorphism of crystalline drugs is a common phenomenon. However, the number of
      reported polymorphic cocrystals is very limited. In this work, the synthesis and
      solid-state characterization of a polymorphic cocrystal composed of sulfadimidine
      (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid
      assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has
      been previously reported, was formed. By spray drying, a new polymorphic form
      (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be
      obtained by solvent evaporation from ethanol and acetone. Structure determination
      of the form II cocrystal was calculated using high-resolution X-ray powder
      diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH
      and predicted by a model established for a two amphoteric component cocrystal.
      The form I cocrystal was found to be thermodynamically more stable in aqueous
      solution than form II, which showed transformation to form I. Dissolution studies
      revealed that the dissolution rate of SD from both cocrystals was enhanced when
      compared with a physical equimolar mixture and pure SD. (c) 2015 Wiley
      Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1385
      1398, 2015. 

PMID- 25605026
TI  - Comparison of toxicogenomics and traditional approaches to inform mode of action
      and points of departure in human health risk assessment of benzo[a]pyrene in
      drinking water.
AB  - Toxicogenomics is proposed to be a useful tool in human health risk assessment.
      However, a systematic comparison of traditional risk assessment approaches with
      those applying toxicogenomics has never been done. We conducted a case study to
      evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene
      (BaP), a well-studied carcinogen, for drinking water exposures. Our study was
      intended to compare methodologies, not to evaluate drinking water safety. We
      compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3)
      approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and
      mice exposed to BaP to determine if these data could provide insight into BaP's
      mode of action (MOA) and derive tissue-specific points of departure (POD). Our
      global gene expression analysis supported that BaP is genotoxic in mice and
      allowed the development of a detailed MOA. Toxicogenomics analysis in human
      lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed
      pathways with animal tissues. Quantitatively, the PODs for traditional and
      transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lungs
      0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which
      applied toxicogenomics in the absence of apical toxicology data, demonstrates
      that this approach provides useful information in data-poor situations. Overall,
      our study supports the use of toxicogenomics as a relatively fast and cost
      effective tool for hazard identification, preliminary evaluation of potential
      carcinogens, and carcinogenic potency, in addition to identifying current
      limitations and practical questions for future work.

PMID- 25605032
TI  - Should all branch-duct intraductal papillary mucinous neoplasms be resected?
AB  - BACKGROUND: The relationship between branch-duct intraductal papillary mucinous
      neoplasms (IPMNs) and malignancy remains controversial and difficult to assess.
      METHODS: Between January 1, 1999 and January 1, 2013, we identified 84 patients
      with IPMN who underwent resection. RESULTS: Preoperatively, 55 patients underwent
      endoscopic ultrasounds and 58 underwent biopsy. Only 7 lesions were specified
      preoperatively as branch-duct, which inconsistently correlated with the surgical
      specimen. Of the 82 patients where the duct was specified, there were 33
      malignant lesions. There was no correlation between branch-duct origin and
      invasive carcinoma. Malignant tumor size did not significantly differ by the duct
      of origin. Of the 28 patients with invasive carcinoma, branch-duct lesions were
      significantly associated with the presence of positive lymph nodes, perineural
      invasion, and lymphovascular invasion. CONCLUSIONS: Our study supports the
      resection criteria for branch-duct IPMN based on size and symptoms. However, it
      also questions the reliability of our preoperative testing to rule out malignant
      branch-duct IPMN lesions.

PMID- 25605033
TI  - Esophageal atresia and transitional care--step 1: a systematic review and meta
      analysis of the literature to define the prevalence of chronic long-term
      problems.
AB  - BACKGROUND: Esophageal atresia (EA) is a rare congenital anomaly with high
      infantile survival rates. The aim of this study was to outline the prevalence of
      common long-term problems associated with EA repair in patients older than 10
      years of age. DATA SOURCES: Original papers were identified by systematic
      searching of MEDLINE and EMBASE databases from January 1993 to July 2014. Fifteen
      articles (907 EA patients) met inclusion criteria. CONCLUSIONS: This is the first
      systematic review aiming to quantify the prevalence of the long-term problems
      associated with EA. The main active medical conditions (pooled estimated
      prevalence) identified were the following: dysphagia (50.3%), gastroesophageal
      reflux disease with (40.2%) or without (56.5%) histological esophagitis,
      recurrent respiratory tract infections (24.1%), doctor-diagnosed asthma (22.3%),
      persistent cough (14.6%), and wheeze (34.7%). The prevalence of Barrett's
      esophagus (6.4%) was 4 and 26 times higher than the adult (1.6%) and pediatric
      (.25%) general populations. Adult and pediatric practitioners should focus on how
      to develop effective long-term follow-up and transitional care for these
      patients.

PMID- 25605034
TI  - Differential reactivity of the inner and outer positions of Au25(SCH2CH2Ph)18
      dimeric staples under place exchange conditions.
AB  - The kinetic analysis of the place exchange reaction on the neutral
      Au25(SCH2CH2Ph)18 cluster by using 4-fluorobenzylthiol and a series of
      substituted arylthiols allowed us to establish, for the first time, that the
      selectivity for the inner and outer positions of the dimeric staples of the
      cluster can be modulated by using incoming thiols with different structures. 

PMID- 25605035
TI  - A correlation between diet and longevity characterization by means of element
      profiles in healthy people over 80 years from a Chinese longevous region.
AB  - Monitoring the element concentrations in the human body is of critical importance
      for health and longevity. In order to explore the formation mechanism of
      longevity from the perspective of the body's element loads, this study
      investigated the prominent feature of element profiles in healthy people over 80
      years from Bama County (China), a famous longevous region (LR). The element
      profiles in nails of elderly people from the LR and a non-longevous region were
      determined by inductively coupled plasma mass spectrometry, using orthogonal
      projections to latent structures discriminant analysis (OPLS-DA) for pattern
      recognition. As a result, four characteristic elements closely related to the
      healthy elderly people from LR, including Cr, Fe, Mn, and Co, were identified.
      The concentrations of Cr, Fe, Mn, and Co were significantly increased in the LR
      group (p < 0.05). The values of fold change of Cr, Fe, Mn, and Co were 3.00,
      2.46, 2.24, and 2.21, respectively. These characteristic elements could provide
      an important material guarantee for health and longevity of elderly people in the
      LR. The further correlation analysis revealed significant positive correlations
      between the Sr (r = 0.886), Mn (r = 0.873), Ni (r = 0.786), and Co (r = 0.738)
      concentrations in nails of elderly people and those in drinking water.
      Furthermore, significant positive correlations were found between the Se (r =
      0.940), Mn (r = 0.833), and Fe (r = 0.733) concentrations in nails and their
      dietary intake. Consequently, the observations suggested that diet could provide
      extraordinary reference information in terms of reflecting the feature of element
      profiles in healthy elderly people over 80 years from the LR.

PMID- 25605036
TI  - Dental pulp stem cells suppress the proliferation of lymphocytes via transforming
      growth factor-beta1.
AB  - Dental pulp stem cells (DPSCs) possess self-renewal capability, multi-lineage
      differentiation potential, and can generate a dentin-pulp-like tissue in vivo,
      which is promising for tooth regeneration. To enlarge the cells resource of DPSCs
      and explore the feasibility of DPSCs-mediated immune therapy, it is prerequisite
      to investigate the immunological properties of DPSCs and the underlying
      mechanisms. Human DPSCs and peripheral blood mononuclear cells were isolated and
      cultured. Then we used lymphocytes proliferation assays, cytokines detection,
      Transwell cultures, neutralization experiments, and flow cytometry to examine the
      in vitro immune characteristics of DPSCs. We found that DPSCs failed to stimulate
      allogeneic T cells proliferation and suppressed T cells proliferation, B cells
      proliferation, and mixed lymphocyte reaction. In addition, DPSCs could up
      regulate IL-10, down-regulate the production of IL-2, IL-17, and IFN-gamma, and
      did not affect the production of IL-6. Monoclonal antibody against transforming
      growth factor-beta1 restored the T cells proliferation inhibited by DPSCs.
      Moreover, the population of regulatory T cells increased significantly and T
      helper 17 cells decreased significantly in peripheral blood mononuclear cells co
      cultured with DPSCs. These data confirmed that DPSCs are low immunogenic, could
      inhibit the proliferation of lymphocytes, regulate the production of cytokines in
      vitro, and the secretion of transforming growth factor-beta1 may be involved in
      this event. 

PMID- 25605037
TI  - To the editor.

PMID- 25605039
TI  - Defining the electrocardiogram in the neonate with hypoplastic left heart
      syndrome.
AB  - Hypoplastic left heart syndrome (HLHS) is a severe form of congenital heart
      disease characterized by underdevelopment of the left heart. There has been no
      previously defined "classic" ECG pattern in a large homogenous population of
      patients with HLHS. We performed a retrospective review of ECGs from neonates
      with HLHS from 2001 to 2011 with electrocardiograms available prior to surgical
      intervention. Eighty-nine neonates met the inclusion criteria and were compared
      to a control population. HLHS patients had a longer PR interval 108 +/- 18 versus
      98 +/- 11 ms (p < 0.05), a wider QRS complex 84 +/- 17 versus 54 +/- 5 ms (p <
      0.05), lower voltage S waves in V1 2.0 +/- 3.3 versus 5.8 +/- 4.6 mm (p < 0.001)
      or absent S waves in V1 52 versus 4 % (p < 0.001) and lower voltage R waves in V6
      7.8 +/- 4.8 versus 9.3 +/- 4.2 mm (p < 0.05). Patients with HLHS were more likely
      to have absent Q waves in the lateral precordial leads 78 versus 0 % (p < 0.001)
      and inferior leads 20 versus 1 % (p < 0.001) and an abnormal frontal plane QRS
      axis 26 versus 11 % (p < 0.05). HLHS patients were more likely to have a
      preexcited appearance 11 versus 0 % (p = 0.001). Despite these findings, 20 % of
      patients with HLHS had a normal ECG. Compared to age-matched controls, patients
      with HLHS were more likely to exhibit a longer PR interval, a wider QRS complex,
      decreased left-sided forces, an absence of septal Q waves in the inferior and
      lateral leads, an abnormal frontal plane QRS axis and a preexcited appearance.

PMID- 25605038
TI  - Quantification and significance of diffuse myocardial fibrosis and diastolic
      dysfunction in childhood hypertrophic cardiomyopathy.
AB  - The purpose of this study was to evaluate the presence of diffuse myocardial
      fibrosis in children and adolescents with hypertrophic cardiomyopathy (HCM) and
      to assess associations with echocardiographic and clinical parameters of disease.
      While a common end point in adults with HCM, it is unclear whether diffuse
      myocardial fibrosis occurs early in the disease. Cardiac magnetic resonance (CMR)
      estimation of myocardial post-contrast longitudinal relaxation time (T1) is an
      increasingly used method to estimate diffuse fibrosis. T1 measurements were taken
      using standard multi-breath-hold spoiled gradient echo phase-sensitive inversion
      recovery CMR before and 15 min after the injection of gadolinium. The tissue
      blood partition coefficient was calculated as a function of the ratio of T1
      change of myocardium compared with blood. An echocardiogram and blood brain
      natriuretic peptide (BNP) levels were obtained on the day of the CMR. Twelve
      controls (mean age 12.8 years; 7 male) and 28 patients with HCM (mean age 12.8
      years; 21 male) participated. The partition coefficient for both septal (0.27 +/-
      0.17 vs. 0.13 +/- 0.09; p = 0.03) and lateral walls (0.22 +/- 0.09 vs. 0.07 +/-
      0.10; p < 0.001) was increased in patients compared with controls. Eight patients
      had overt areas of late gadolinium enhancement (LGE). These patients did not show
      increased partition coefficient compared with those without LGE (0.27 +/- 0.15
      vs. 0.27 +/- 0.19 and 0.22 +/- 0.09 vs. 0.22 +/- 0.09; p = 0.95 and 0.98,
      respectively). However, patients who were symptomatic (dyspnea, arrhythmia and/or
      chest pain) had higher lateral wall partition coefficient than asymptomatic HCM
      patients (0.27 +/- 0.08 vs. 0.17 +/- 0.08; p = 0.006). Similarly, patients with
      raised BNP (>100 pg/ml) had raised lateral wall coefficients (0.27 +/- 0.07 vs.
      0.20 +/- 0.07; p = 0.03), as did those with traditional risk factors for sudden
      death (0.27 +/- 0.06 vs. 0.18 +/- 0.08; p = 0.007). Diffuse fibrosis, measured by
      the partition coefficient technique, is demonstrable in children and adolescents
      with HCM. Markers of fibrosis show an association with symptoms and raised serum
      BNP. Further study of the prognostic implication of this technique in young
      patients with HCM is warranted.

PMID- 25605040
TI  - Solvent induced single-crystal to single-crystal structural transformation and
      concomitant transmetalation in a 3D cationic Zn(II)-framework.
AB  - A 3D cationic Zn(II) framework, based on Zn2(CO2)4 paddle-wheel secondary
      building units (SBUs) and Zn16(CO2)32 polyhedral supramolecular building blocks
      (SBBs), has been synthesized. At room temperature, the framework undergoes guest
      solvent triggered reversible structural transformation and concomitant Zn(II) to
      Cu(II) transmetalation in a single-crystal to single-crystal fashion.

PMID- 25605042
TI  - Dactylosporangium sucinum sp. nov., isolated from Thai peat swamp forest soil.
AB  - The actinomycete strain RY35-23(T) was isolated from peat swamp forest soil in
      Thailand. The taxonomic position of this strain was determined using polyphasic
      approach. Strain RY35-23(T) showed typical morphology and chemical properties
      similar to the members in the genus Dactylosporangium. On the basis of 16S
      ribosomal RNA gene analysis, this strain was closely related to Dactylosporangium
      fulvum JCM 5631(T) (98.94%), D. roseum JCM 3364(T) (98.87%) and D. darangshiense
      JCM 17441(T) (98.86%). The DNA-DNA relatedness between strain RY35-23(T) and its
      closely related species was lower than 70%, the cutoff level for assigning
      strains to the same species. On the basis of these results mentioned, the strain
      RY35-23(T) could be distinguished from its closely related type strains and
      represents a novel species of the genus Dactylosporangium, for which the name
      Dactylosporangium sucinum (type strain RY35-23(T)=JCM 19831(T)=TISTR 2212(T)=PCU
      333(T)) is proposed.

PMID- 25605041
TI  - Neo-sex chromosomes of Ronderosia bergi: insight into the evolution of sex
      chromosomes in grasshoppers.
AB  - Sex chromosomes have evolved many times from morphologically identical autosome
      pairs, most often presenting several recombination suppression events, followed
      by accumulation of repetitive DNA sequences. In Orthoptera, most species have an
      X0? sex chromosome system. However, in the subfamily Melanoplinae, derived
      variants of neo-sex chromosomes (neo-XY? or neo-X1X2Y?) emerged several times.
      Here, we examined the differentiation of neo-sex chromosomes in a Melanoplinae
      species with a neo-XY?/XX? system, Ronderosia bergi, using several approaches:
      (i) classical cytogenetic analysis, (ii) mapping via fluorescent in situ
      hybridization of some selected repetitive DNA sequences and microdissected sex
      chromosomes, and (iii) immunolocalization of distinct histone modifications. The
      microdissected sex chromosomes were also used as sources for Polymerase chain
      reaction (PCR) amplification of RNA-coding multigene families, to study variants
      related to the sex chromosomes. Our data suggest that the R. bergi neo-Y has
      become differentiated after its formation by a Robertsonian translocation and
      inversions, and has accumulated repetitive DNA sequences. Interestingly, the ex
      autosomes incorporated into the neo-sex chromosomes retain some autosomal post
      translational histone modifications, at least in metaphase I, suggesting that the
      establishment of functional modifications in neo-sex chromosomes is slower than
      their sequence differentiation. 

PMID- 25605044
TI  - Variation in phytochemicals and bioactivity of the fruits of Eleutherococcus
      species cultivated in Poland.
AB  - Neither the chemical profile and bioactivity of the fruits of Eleutherococcus
      species cultivated in Poland nor the influence of long-term domestic storage of
      the fruits are known. No changes in the phenols and flavonoids content in the
      freshly dried and 1-year storage fruits of Eleutherococcus senticosus and
      Eleutherococcus henryi were found. The 1-year storage fruits of both species
      exhibited a very high concentration of Mn, Zn and Cu (mg/kg) compared with the
      fresh-dried fruits. Spathulenol, beta-longipinene and iso-longifolol were
      predominant essential oil compounds. It was observed that a high capacity of the
      freshly dried E. senticosus fruits were able to scavenge DPPH* and inhibit Hyal
      (EC50 0.1 mg/mL; IC50 0.58 mg/mL). Due to their health and pharmacological
      benefits, a better understanding of the impact of the climate change is important
      to increase the pharmacological utility of the extracts.

PMID- 25605045
TI  - Does combined clinical and ultrasound assessment allow selection of individuals
      with rheumatoid arthritis for sustained reduction of anti-tumor necrosis factor
      therapy?
AB  - OBJECTIVE: To investigate whether a strategy combining clinical and ultrasound
      (US) assessment can select individuals with rheumatoid arthritis (RA) for
      sustained dose reduction of anti-tumor necrosis factor (anti-TNF) therapies.
      METHODS: As part of a real-world approach, patients with RA receiving anti-TNF
      therapies were reviewed in a dedicated biologic therapy clinic. Patients not
      taking oral corticosteroids with both Disease Activity Score in 28 joints (DAS28)
      remission (<=2.6) and absent synovitis on power Doppler US (PDUS 0) for >6 months
      were invited to reduce their anti-TNF therapy dose by one-third. RESULTS: Between
      January 2012 and February 2014, a total of 70 patients underwent anti-TNF dose
      reduction. Combined DAS28 and PDUS remission was maintained by 96% of patients at
      3 months followup, 63% at 6 months, 37% at 9 months, and 34% at 18 months
      followup. However, 88% of patients maintained at least low disease activity (LDA)
      with DAS28 <3.2 and PDUS <=1 at 6 months. The addition of PDUS identified 8
      patients (25% of those that flared) in DAS28 remission, with subclinically active
      disease. Those who maintained dose reduction were more likely to be rheumatoid
      factor (RF) negative (46% versus 17%; P = 0.03) and have lower DAS28 scores at
      biologic therapy initiation (5.58 versus 5.96; P = 0.038). CONCLUSION: Combined
      clinical and US assessment identifies individuals in remission who may be
      suitable for anti-TNF dose reduction and enhances safe monitoring for subclinical
      disease flares. Despite longstanding severe RA, a subset of our cohort sustained
      prolonged DAS28 and PDUS remission. LDA at biologic therapy initiation and RF
      status appeared predictive of sustained remission.

PMID- 25605046
TI  - Morphological and comparative genomic analyses of pathogenic and non-pathogenic
      Fusarium solani isolated from Dalbergia sissoo.
AB  - Sissoo or shisham (Dalbergia sissoo Roxb.) is one of the finest wood of South
      Asia. Fusarium solani is a causal organism of sissoo wilt, decline, or dieback.
      It is also a potential causal organism associated with other valuable tree
      species. Thirty-eight Fusarium isolates including 24 F. solani and 14 Fusarium
      sp., were obtained in 2005 from different geographical locations in India. All 38
      (18 pathogenic and 20 non-pathogenic) isolates were characterized for genomic
      analysis, growth behaviour, pigmentation and sensitivity to carbendazim. Based on
      growth pattern, growth rate, pigmentation and sensitivity to carbendazim, all 38
      isolates showed a wide range of variability, but no correlation with
      pathogenicity or geographical distribution. Three techniques were used for
      comparative genomic analysis: random amplified polymorphic DNA (RAPD); inter
      simple sequence repeats (ISSR); and simple sequence repeats (SSR). A total of 90
      primers targeting different genome regions resulted a total of 1159 loci with an
      average of 12.88 loci per primer. These primers showed high genomic variability
      among the isolates. The maximum loci (14.64) per primer were obtained with RAPD.
      The total variation of the first five principal components for RAPD, ISSR, SSR
      and combined analysis were estimated as 47.42, 48.21, 46.30 and 46.78 %,
      respectively. Among the molecular markers, highest Pearson correlation value (r =
      0.957) was recorded with combination of RAPD and SSR followed by RAPD and ISSR (r
      = 0.952), and SSR and ISSR (r = 0.942). The combination of these markers would be
      similarly effective as single marker system i.e. RAPD, ISSR and SSR. Based on
      polymorphic information content (PIC = 0.619) and highest coefficient (r =
      0.995), RAPD was found to be the most efficient marker system compared to ISSR
      and SSR. This study will assist in understanding the population biology of wilt
      causing phytopathogen, F. solani, and in assisting with integrated disease
      management measures.

PMID- 25605043
TI  - Novel terpenes generated by heterologous expression of bacterial terpene synthase
      genes in an engineered Streptomyces host.
AB  - Mining of bacterial genome data has revealed numerous presumptive terpene
      synthases. Heterologous expression of several putative terpene synthase genes in
      an engineered Streptomyces host has revealed 13 newly discovered terpenes whose
      GC-MS and NMR data did not match with any known compounds in spectroscopic
      databases. Each of the genes encoding the corresponding terpene synthases were
      silent in their parent microorganisms. Heterologous expression and detailed NMR
      spectroscopic analysis allowed assignment of the structures of 13 new cyclic
      terpenes. Among these newly identified compounds, two were found to be linear
      triquinane sesquiterpenes that have never previously been isolated from bacteria
      or any other source. The remaining 11 new compounds were shown to be diterpene
      hydrocarbons and alcohol, including hydropyrene (1), hydropyrenol (2),
      tsukubadiene (11) and odyverdienes A (12) and B (13) each displaying a novel
      diterpene skeleton that had not previously been reported. 

PMID- 25605047
TI  - Bioethanol production from the dry powder of Jerusalem artichoke tubers by
      recombinant Saccharomyces cerevisiae in simultaneous saccharification and
      fermentation.
AB  - It has been found that recombinant Saccharomyces cerevisiae 6525 can produce high
      concentration of ethanol in one-step fermentation from the extract of Jerusalem
      artichoke tubers or inulin. However, the utilization rate of raw materials was
      low and the fermentation process was costly and complicated. Therefore, in this
      study, after the optimum processing conditions for ethanol production in fed
      batch fermentation were determined in flask, the recombinant S. cerevisiae 6525
      was first used to produce ethanol from the dry powder of Jerusalem artichoke
      tubers in 5-L agitating fermentor. After 72 h of fermentation, around 84.3 g/L
      ethanol was produced in the fermentation liquids, and the conversion efficiency
      of inulin-type sugars to ethanol was 0.453, or 88.6 % of the theoretical value of
      0.511. This study showed high feasibility of bioethanol industrial production
      from the Jerusalem artichoke tubers and provided a basis for it in the future. 

PMID- 25605049
TI  - Vale John Spencer.

PMID- 25605048
TI  - A survey of anesthesiologists' role, trust in anesthesiologists, and knowledge
      and fears about anesthesia among predominantly Hispanic patients from an inner
      city county preoperative anesthesia clinic.
AB  - STUDY OBJECTIVE: To determine the difference between the Hispanic and non
      Hispanic public's knowledge about anesthesia, anesthesiologist's expertise, and
      role of the anesthesiologist in and out of the operating room (OR). DESIGN: Cross
      sectional survey. SETTING: Los Angeles inner-city county hospital preoperative
      anesthesia clinic. PATIENTS: Predominantly Hispanic population. INTERVENTIONS: A
      54-question survey in English and Spanish was distributed to adult patients.
      MEASUREMENTS: Demographic data, knowledge of the anesthesiologist's
      roles/responsibilities, knowledge of anesthesia, trust in anesthesiologists, and
      fears related to anesthesia were collected. Descriptive analysis and multiple
      regression analysis of the data were used to report knowledge, trust, and fear,
      and the predictive role of patient characteristics. MAIN RESULTS: 300 (88% of
      eligible pts) completed the survey. Patient demographics were as follows:
      Hispanics (73%), female (63%), mean age 47 +/- 14 years, high school-educated or
      below (71%), previous surgery (67%), possessing a chronic medical condition
      (49%), self-reported health of fair to poor (58%). Seventy percent of patients
      recognized anesthesiologists as specially trained doctors. Mean +/- SD trust
      scores in doctors were 2.6 +/- 1.2 out of a maximum 4. Patients with a better
      perception of their self-health (P < 0.01) and with higher knowledge scores (P <
      0.01) had significantly higher trust in the doctors. Women (P = 0.01) patients,
      those patients with chronic medical condition (P < 0.02), and patients with
      greater knowledge scores had greater fear or concerns about anesthesia. Mean +/-
      SD knowledge score about anesthesia was 6.3 +/- 2.8 (range 0-13). Patients who
      had surgery previously (P < 0.01) had higher knowledge scores. CONCLUSION: Most
      Hispanic patients believe that anesthesiologists are specialist doctors and that
      they put patients to sleep, but these patients are uncertain of their exact role
      or function during surgery or outside of the OR. High concerns or fears about
      devastating but rare complications of anesthesia remain. Educational efforts
      should be directed at this group especially, with the goal of alleviating
      preoperative anxiety.

PMID- 25605050
TI  - Failures of translational pain research: can they be due to misinterpretation of
      pain-related nomenclature?

PMID- 25605051
TI  - NO-ting a putative mechanism by which anti-migraine drugs mitigate trigeminal
      neuropathic pain.

PMID- 25605052
TI  - The Enrico Greppi Award 2015--17th Edition.

PMID- 25605053
TI  - Cardiovascular risk and events after liver transplantation. Experiences from 313
      consecutive transplants with a follow-up of 20 years.
AB  - Cardiovascular diseases (CVD) are the third leading cause of late death after
      liver transplantation (LT). The old PROCAM score was described in males (aged 35
      65 yr) to estimate cardiovascular events after LT. New PROCAM is now available to
      estimate risks for cardiovascular events in both genders and for a wider age
      range (25-75 yr). We tested old and new PROCAM in long-term follow-up (10 and 20
      yr) and described CVD risk factors, kidney function, and immunosuppression over
      two decades. A retrospective study of 313 consecutive LTs was conducted. At 10
      (T2) and 20 (T3) yr, patients were screened for cardiovascular events, and for T1
      (0.5 yr) and T2, CVD risk factors were recorded and old and new PROCAM
      calculated. PROCAM estimates were compared with observed events. CVD risk factors
      increased significantly over time and kidney function decreased. Between T1 and
      T2 in males, fewer events were observed (o) than estimated (e) (males: o: 3 vs.
      e: 6.05-9.88; females o: 2 vs. e: 1.35-4.21). For both genders, new PROCAM was
      appropriate between T2 and T3 (males o: 8; e: 4.5-8.57; females o: 2; e: 1.2
      4.46). New PROCAM sufficiently estimates cardiovascular risk after LT, while
      overestimation in T1-T2 may be due to strict surveillance. 

PMID- 25605054
TI  - The effect on structural and solvent water molecules of substrate binding to
      ferric horseradish peroxidase.
AB  - Ultrafast, multi-dimensional infrared spectroscopy, in the form of 2D-IR and pump
      probe measurements, has been employed to investigate the effect of substrate
      binding on the structural dynamics of the horseradish peroxidase (HRP) enzyme.
      Using nitric oxide bound to the ferric haem of HRP as a sensitive probe of local
      dynamics, we report measurements of the frequency fluctuations (spectral
      diffusion) and vibrational lifetime of the NO stretching mode with
      benzohydroxamic acid (BHA) located in the substrate-binding position at the
      periphery of the haem pocket, in both D2O and H2O solvents. The results reveal
      that, with BHA bound to the enzyme, the local structural dynamics are insensitive
      to H/D exchange. These results are in stark contrast to those found in studies of
      the substrate-free enzyme, which demonstrated that the local chemical and dynamic
      environment of the haem ligand is influenced by water molecules. In light of the
      large changes in solvent accessibility caused by substrate binding, we discuss
      the potential for varying roles for the solvent in the haem pocket of HRP at
      different stages along the reaction coordinate of the enzymatic mechanism. 

PMID- 25605055
TI  - Inhibition of abasic site cleavage in bubble DNA by multifunctional protein YB-1.
AB  - Y-box binding protein 1 (YB-1) is widely known to participate in a multiple DNA
      and RNA processing events in the living cell. YB-1 is also regarded as a putative
      component of DNA repair. This possibility is supported by relocalization of YB-1
      into the nucleus following genotoxic stress. Increased affinity of YB-1 for
      damaged DNA, especially in its single-stranded form, and its functional
      interaction with proteins responsible for the initiation of apurinic/apyrimidinic
      (AP) site repair, namely, AP endonuclease 1 and DNA glycosylase NEIL1, suggest
      that YB-1 could be involved in the repair of AP sites as a regulatory protein.
      Here we show that YB-1 has a significant inhibitory effect on the cleavage of AP
      sites located in single-stranded DNA and in DNA bubble structures. Such
      interference may be considered as a possible mechanism to prevent single-stranded
      intermediates of DNA replication, transcription and repair from being converted
      into highly genotoxic DNA strand breaks, thus allowing the cell to coordinate
      different DNA processing mechanisms.

PMID- 25605056
TI  - Perspective for the development of companion diagnostics and regulatory landscape
      to encourage personalized medicine in Japan.
AB  - BACKGROUND: On July 1st, 2013, the Ministry of Health, Labor and Welfare (MHLW)
      issued an official notification regarding the co-development of companion
      diagnostics (CDx) with a drug which requires any exclusive diagnostic test or
      medical device to predict efficacy or adverse reactions to the drug. The main
      frame and contents in the MHLW's notification are quite similar to the summaries
      in the final guidance issued by the US Food and Drug Administration (FDA) on
      August 6th, 2014 Guidance for Industry and Food and Drug Administration Staff (In
      Vitro Companion Diagnostic Devices, [2014] ), and these recommend industries to
      develop, study and submit CDx and the corresponding drug contemporaneously as
      much as possible. Following the MHLW's notification, the Pharmaceutical and
      Medical Device Agency (PMDA) notified on December 26th, 2013, "the technical
      guidance for co-development of CDx and the drug" that mentioned the regulatory
      requirements for clinical trial of the drug and CDx as well as analytical
      validity of CDx required for the trials. These official notifications from the
      Ministry and the Agency may be useful for pharmaceutical and diagnostics makers
      to understand how they should co-develop and validate CDx for clinical trials and
      regulatory submission. However, since the most anticipated technologies such as
      the next generation sequencer (NGS) are more complex and its medical risks could
      be high level, the existing regulatory system focusing on only diagnostics
      reagents and devices that are developed and manufactured by in vitro diagnostics
      (IVD) makers may be no longer suitable for the characteristics of CDx for the
      future.As an increase of clinical needs for multiple biomarkers assay by DNA
      sequencer, on November 19th, 2013, the FDA cleared 510 K for NGS and its
      universal kit. On October 3rd, 2014, moreover, the agency notified two drafts of
      guidance (Anticipated Details of the Draft Guidance for Industry, Food and Drug
      Administration Staff, and Clinical Laboratory in Framework for Regulatory
      Oversight of Laboratory Developed Tests (LDTs), [2014]; Anticipated Details of
      the Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical
      Laboratory in FDA Notification and Medical Device Reporting for Laboratory
      Developed Tests (LDT), [2014]) for oversight of laboratory developed tests (LDTs)
      with medium or high medical risks. These FDA's strategic decisions and new
      regulatory frameworks may allow the clinical laboratories to develop and perform
      more easily NGS-based CDx under the certification of Clinical Laboratory
      Improvement Amendments (CLIA). However, neither law nor regulated quality
      management system similar to the CLIA exists in Japan. To effectively validate
      LDTs and NGS for medical practice, Japan should learn more the current regulatory
      changes and initiatives in the US, as well as to reform the regulatory frameworks
      and create any regulated quality management system for clinical laboratory
      testing to be reimbursed.

PMID- 25605057
TI  - Puerarin ameliorates hepatic steatosis by activating the PPARalpha and AMPK
      signaling pathways in hepatocytes.
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by the hepatic
      manifestation of metabolic syndrome and is the leading cause of chronic liver
      disease. Steatohepatitis plays a critical role in the process resulting in liver
      fibrosis and cirrhosis. Puerarin is a herbal product widely used in Asia, and is
      believed to have therapeutic benefits for alleviating the symptoms of
      steatohepatitis. The present study was designed to investigate the effects and
      mechanisms of action of puerarin in reducing lipid accumulation in oleic acid
      (OA)-treated HepG2 cells. Hepatocytes were treated with OA with or without
      puerarin to observe lipid accumulation by Oil Red O staining. We also examined
      hepatic lipid contents (e.g., triacylglycerol and cholesterol) following
      treatment with puerarin. Western blot analysis and reverse transcription
      polymerase chain reaction (RT-PCR) were used to measure sterol regulatory element
      binding protein (SREBP)-1, fatty acid synthase (FAS), peroxisome proliferator
      activated receptor alpha (PPARalpha) and adenosine 5'-monophosphate (AMP)
      activated protein kinase (AMPK) protein and mRNA expression, respectively. Our
      results revealed that puerarin suppressed OA-induced lipid accumulation, and
      reduced the triacylglycerol and cholesterol levels. Furthermore, puerarin
      decreased the expression levels of lipogenic enzymes, such as FAS and SREBPs, and
      increased the expression levels of PPARalpha, which are critical regulators of
      hepatic lipid metabolism through the AMPK signaling pathway. These results
      indicate that puerarin has the same ability to activate AMPK, and reduce SREBP-1
      and FAS expression, thus inhibiting hepatic lipogenesis and increasing hepatic
      antioxidant activity. We found that puerarin exerted a regulatory effect on lipid
      accumulation by decreasing lipogenesis in hepatocytes. Therefore, puerarin
      extract may have therapeutic benefits in the treatment of fatty liver and lipid
      related metabolic disorders.

PMID- 25605058
TI  - Ultrasound-guided dorsal penile nerve block for ED paraphimosis reduction.
AB  - Adequate anesthesia for emergency department management of painful penile
      conditions such as paraphimosis or priapism is often both technically challenging
      and inconsistent using traditional landmark-based techniques of the dorsal penile
      block (DPB). The pudendal nerves branch to form the paired dorsal nerves of the
      penis providing sensory innervation to the skin of both the dorsal and ventral
      aspects of the penis. "Blind" DPB techniques tend to rely on subtle tactile
      feedback from the needle and visual landmark approximation to identify the
      appropriate subpubic fascial compartment for injection. The landmark-based DPB is
      not standardized with options including "10 o'clock and 2 o'clock" infrapubic
      injections with or without ventral infiltration or a ring block. Given the lack
      of standardization and inherent technical imprecision with the landmark-based
      DPB, large volumes of local anesthetic (up to 50 mL) are sometimes required to
      achieve a clinically adequate block. In addition, inadvertent injection into the
      corpora cavernosa may occur. More recently, an ultrasound-guided approach has
      been developed. Using ultrasound, the dorsal penile nerves can be precisely
      targeted in the fascial compartment just deep to Buck fascia, potentially
      increasing block success rate and reducing the need for large local anesthetic
      volumes. Herein, we report the first adult case of an ultrasound-guided dorsal
      penile nerve block performed in the emergency department for the reduction of a
      paraphimosis and review the relevant penile anatomy and technical details of the
      procedure.

PMID- 25605060
TI  - Luseogliflozin and other sodium-glucose cotransporter 2 inhibitors: no enemy but
      time?
AB  - Glycosuria is being increasingly recognised as not only a symptom but also as a
      novel therapeutic approach in the management of type 2 diabetes mellitus (T2DM).
      This is accomplished through sodium glucose co-transporter 2 (SGLT2) inhibitors.
      Consequently, the safety and efficacy of these new agents have been thoroughly
      studied, both in randomised controlled trials and in systematic reviews and meta
      analyses. More recently, a review on the mechanism of action, clinical efficacy
      and safety of luseogliflozin, a new highly selective SGLT2 inhibitor approved and
      launched in Japan for T2DM, has documented that this drug lowers plasma glucose
      concentration and body weight, and that it exhibits benefits in other metabolic
      parameters with a good safety profile. Despite the promising characteristics of
      this drug, important issues await consideration. These include the question as to
      when and to whom early use of SGLT2 inhibitors would be most suitable, as well as
      instructions on reduction of sulfonylurea dosage during add-on treatment. Further
      important questions are long-term safety concerns and cost-effectiveness of this
      new therapeutic class. Finally, we need to know more about the potential
      differences between the various SGLT2 inhibitors, as such differences might prove
      clinically useful in selection of hypoglycaemic agents. 

PMID- 25605059
TI  - Effective suppression of nitric oxide production by HX106N through
      transcriptional control of heme oxygenase-1.
AB  - Heme oxygenase-1 (HO-1) has been suggested to be a key neuroprotective enzyme
      because of its widespread distribution in the brain as well as its strong
      antioxidative effects. HX106N, a water-soluble botanical formulation, has
      previously been demonstrated to prevent amyloid beta-induced memory impairment
      and oxidative stress in mice by upregulating HO-1 levels. In this study, the
      underlying molecular mechanisms of HX106N-induced HO-1 expression were
      investigated using BV-2 cells, a murine microglial cell line, and primary
      microglia. Treatment with HX106N induced the expression of HO-1 at the
      transcriptional level through the stress-responsive element-containing enhancer
      present in the ho-1 promoter. Nuclear factor E2-related factor 2 (Nrf2) was
      activated in cells treated with HX106N. The results from knockdown assay showed
      that small interfering RNA of Nrf2 attenuated HX106N-mediated HO-1 expression.
      Pharmacological inhibitors of p38 and JNK mitogen-activated protein kinases
      suppressed the HX106N-mediated induction of HO-1. The NF-kappaB signaling pathway
      was activated by HX106N and played a role in HX106N-induced HO-1 expression.
      Furthermore, HO-1 and one of its by-products during the enzymatic degradation of
      heme, CO, were found to be involved in HX106N-mediated suppression of NO
      production. Taken together, these data indicate that HX106N exerts potent
      antioxidative effects by increasing the expression of HO-1 through multiple
      signaling pathways, leading to the suppression of NO production. 

PMID- 25605061
TI  - Comparison of human dermal fibroblasts (HDFs) growth rate in culture media
      supplemented with or without basic fibroblast growth factor (bFGF).
AB  - Basic fibroblast growth factor (bFGF or FGF-2) is a member of the FGF family
      secreted by different kinds of cells like HDFs and it is an important nutritional
      factor for cell growth and differentiation. The HDFs release bFGF in culture
      media at very low. The present study aims to investigate the HDFs growth rate in
      culture media supplemented either with or without bFGF. In brief, HDFs were
      isolated from human foreskin sample and were cultured in vitro in media
      containing bFGF and lack of this factor. The cells growth rate was calculated by
      trypan blue. The karyotyping was performed using G-banding to investigate the
      chromosomal abnormality of HDFs in both groups. Total RNA of each groups were
      extracted and cDNA samples were synthesized then, real-time Q-PCR was used to
      measure the expression level of p27kip1 and cyclin D1 genes normalized to
      internal control gene (GAPDH). The karyotype analysis showed that HDFs cultured
      in media or without bFGF had normal karyotype (46 chromosomes, XY) and
      chromosomal abnormalities were not observed. The cell growth rates in both groups
      were normal with proliferated exponentially but the slope of growth curve in HDFs
      cultured in media containing bFGF was increased. Karyotyp test showed that bFGF
      does not affect on cytogenetic stability of cells. The survey of p27kip1 and
      cyclin D1 genes by real-time Q-PCR showed that the expression level of these
      genes were up-regulated when adding bFGF in culture media (p < 0.05). The
      findings of the present study demonstrate that appropriate supplementation of
      culture media with growth factor like bFGF could enhance the proliferation and
      differentiation capacity of cells and improve cells growth rate. Similarly,
      fibroblast growth factors did not induce any chromosomal abnormality in cells.
      Furthermore, in HDFs cultured in bFGF supplemented media, the p27kip1 and cyclin
      D1 genes were up-regulated and suggesting an important role for bFGF in cell
      cycle regulation and progression and fibroblast division stimulation. It also
      suggests that the effects of bFGF on different cell types with/or without
      production of bFGF or other regulation factors be investigated in future. 

PMID- 25605062
TI  - Cyclic stretch augments production of neutrophil chemokines, matrix
      metalloproteinases, and activin a in human endometrial stromal cells.
AB  - PROBLEM: The aim of this study was to test our hypothesis: Contractile activity
      that occurs in the uterus during menstruation induces biochemical factors that
      enhance remodeling of the endometrium. METHOD OF STUDY: Cyclic stretch, mimicking
      contractile activity during menstruation, was applied to human endometrial
      stromal cells (ESC) using the Flexercell Tension system. The concentration and
      activity of CXCL8, CXCL1, MMPs, and activin A were measured using ELISAs and
      specific assays. Neutrophil chemotactic activity was evaluated using migration
      assays. RESULTS: Cyclic stretch significantly induced ESC secretion of CXCL8 and
      CXCL1 and neutrophil chemotaxis. Stretch also increased MMP-1, MMP-2, and MMP-3
      activity, activin A secretion, and activity in ESC. CONCLUSION: These results
      indicate that the contractile activities of the uterus during menstruation
      contribute to the remodeling of the endometrium, by inducing chemokine secretion,
      MMP expression, activity, and neutrophil chemotaxis.

PMID- 25605063
TI  - A superlattice of alternately stacked Ni-Fe hydroxide nanosheets and graphene for
      efficient splitting of water.
AB  - Cost-effective electrocatalysts based on nonprecious metals for efficient water
      splitting are crucial for various technological applications represented by fuel
      cell. Here, 3d transition metal layered double hydroxides (LDHs) with varied
      contents of Ni and Fe were successfully synthesized through a homogeneous
      precipitation. The exfoliated Ni-Fe LDH nanosheets were heteroassembled with
      graphene oxide (GO) as well as reduced graphene oxide (rGO) into superlattice
      like hybrids, in which two kinds of oppositely charged nanosheets are stacked
      face-to-face in alternating sequence. Heterostructured composites of Ni2/3Fe1/3
      LDH nanosheets and GO (Ni2/3Fe1/3-GO) exhibited an excellent oxygen evolution
      reaction (OER) efficiency with a small overpotential of about 0.23 V and Tafel
      slope of 42 mV/decade. The activity was further improved via the combination of
      Ni2/3Fe1/3 LDH nanosheets with more conductive rGO (Ni2/3Fe1/3-rGO) to achieve an
      overpotential as low as 0.21 V and Tafel plot of 40 mV/decade. The catalytic
      activity was enhanced with an increased Fe content in the bimetallic Ni-Fe
      system. Moreover, the composite catalysts were found to be effective for hydrogen
      evolution reaction. An electrolyzer cell powered by a single AA battery of 1.5 V
      was demonstrated by using the bifunctional catalysts. 

PMID- 25605064
TI  - It's time for consensus on the future of the NHS.
AB  - Guidance on the number of nurses needed in A&E departments was issued last week
      by the National Institute for Health and Care Excellence (NICE). No nurse should
      have to look after more than four patients - and only two if their conditions are
      more serious. The guidance is out for consultation, but hospital managers would
      be well advised to take heed straightaway. 

PMID- 25605065
TI  - Patient acuity should be a factor in A&E staffing equation, says RCN.
AB  - Proposed guidance on minimum staffing levels could help struggling A&Es, but
      should be viewed with caution, according to the RCN. 

PMID- 25605066
TI  - NHS in Wales gets L40 million boost to ease winter pressures.
AB  - The Welsh Government has invested an extra L40 million in the NHS to cope with
      winter pressures. 

PMID- 25605067
TI  - 'Golden hello' could boost staff recruitment at struggling trust.
AB  - Bonuses, gym membership and iPads could be on offer to encourage nurses to take
      jobs with an employer that is struggling to recruit. 

PMID- 25605068
TI  - Union warns of EU trade deal's threat to the NHS.
AB  - There is 'unprecedented' opposition to a major international trade deal that
      critics, including the union Unite, fear could lead to increased privatisation of
      the NHS. 

PMID- 25605069
TI  - Labour would recruit carers for nurse training.
AB  - A new generation of nurses will be recruited from social care if Labour wins the
      general election. 

PMID- 25605070
TI  - Minimum staffing ratios would help tempt ex-nurses back, says Lib Dem.
AB  - Setting minimum nurse staffing levels in Wales would create a working environment
      that tempts former nurses back into the profession, members of the Welsh assembly
      heard. 

PMID- 25605071
TI  - Hugh puts storytelling centre stage.
AB  - Actor Hugh Grant has helped write a book on the benefits of drama and
      storytelling with a friend who has learning disabilities. 

PMID- 25605073
TI  - Night response team cuts A&E admissions.
AB  - A trust has introduced a team of nurses to help monitor adult patients in their
      homes at night in a bid to reduce emergency admissions. 

PMID- 25605074
TI  - NHS managers must keep spending to prevent HCAIs.
AB  - Almost half of patients are prepared to travel 100 miles for care if their local
      hospital has a poor record on infections such as MRSA, research has revealed. 

PMID- 25605075
TI  - NHS Employers support unsocial hours pay, but want reduced rates.
AB  - More than 80 per cent of NHS employers believe staff should receive extra pay for
      working unsocial hours. 

PMID- 25605076
TI  - Charity provides nurse support to thyroid cancer patients.
AB  - Macmillan Cancer Support has appointed its first thyroid cancer information nurse
      specialist to work on its national support line. 

PMID- 25605078
TI  - House of Lords rejects attempts to amend Assisted Dying Bill.
AB  - Lord Falconer's Assisted Dying Bill passed a legislative hurdle after two days of
      debate in the House of Lords. 

PMID- 25605080
TI  - NMC denies prioritising new FtP cases to meet government target.
AB  - The Nursing and Midwifery Council's success in reducing the time it takes to
      handle fitness to practise cases has not been achieved by neglecting older cases,
      according to its chief executive Jackie Smith. 

PMID- 25605088
TI  - Cancer diagnosis.
AB  - Essential facts Around 300,000 people were diagnosed with cancer in England and
      Wales in 2011, and more than one in three people in the UK will develop cancer in
      some form during their lifetime. An early diagnosis is the best way to tackle the
      disease and improve survival rates. However, not enough is being done to identify
      cancer and treat it an early stage, says the National Institute for Health and
      Care Excellence (NICE). 

PMID- 25605082
TI  - DH sets sights on unsocial hours pay in drive for seven-day service.
AB  - The Department of Health (DH) has put itself on a collision course with nurses
      and other NHS workers with its latest threat to their pay. 

PMID- 25605089
TI  - How to spot a nurse killer.

PMID- 25605090
TI  - Bringing back the sparkle.

PMID- 25605091
TI  - Stepping outside your comfort zone.

PMID- 25605103
TI  - The lindsay leg club foundation.
AB  - The Pretty Pins Leg Club in Powys, mid-Wales, is not an exotic dancing nightspot
      but part of a network of 24 UK clubs inspired by the vision of nurse Ellie
      Lindsay. 

PMID- 25605105
TI  - Ebola Tracker app.
AB  - Developer Bryan Ratledge claims his Ebola Tracker app is the only up to date
      mapping application of the 2014 Ebola virus disease outbreak centred in West
      Africa. With this app, you track the Ebola outbreak just as you would track a
      hurricane, or the weather. 

PMID- 25605106
TI  - Ward rounds are an essential component of good basic care.
AB  - In my day, we called intentional rounding 'ward rounds' or 'the back round'. It
      puzzles me that the prime minister is championing a L450,000 study to see if they
      lead to better care (News December 17). 

PMID- 25605107
TI  - Helping patients struggling to pay their prescription charges.
AB  - In his latest column on Medicines Management (Reflections January 7), Matt
      Griffiths responds to the question: 'I have patients who are struggling to pay
      their prescription charges. Is there anything I can do to help?' 

PMID- 25605108
TI  - Everyone is working together to ease the pressures in A&E.
AB  - Nurse consultant Janet Youd, chair of the RCN Emergency Care Association, says
      nurses struggling to cope with unprecedented pressures in A&E departments should
      be awarded an extra half day's annual leave (Online News January 8). 

PMID- 25605109
TI  - Are nurses from the European Union able to get hospital jobs?
AB  - I am a Polish nurse with a master's degree and four years' experience. You kindly
      published a letter from me last year, 'I am banging my head against a brick wall
      to gain registration' (October 29). 

PMID- 25605111
TI  - Children are being let down by their mental health provision.
AB  - Dean-David Holyoake says there have been problems with the provision of Child and
      Adolescent Mental Health Services (CAMHS) since it was founded in 1995
      (Reflections January 7). 

PMID- 25605112
TI  - Chocolates are particularly welcome on the wards in A&E.
AB  - I read with amusement Kat Keogh's article suggesting that nurses should avoid
      eating chocolates given as gifts by patients (News December 17). 

PMID- 25605114
TI  - Values-based recruitment in health care.
AB  - Values-based recruitment is a process being introduced to student selection for
      nursing courses and appointment to registered nurse posts. This article discusses
      the process of values-based recruitment and demonstrates why it is important in
      health care today. It examines the implications of values-based recruitment for
      candidates applying to nursing courses and to newly qualified nurses applying for
      their first posts in England. To ensure the best chance of success, candidates
      should understand the principles and process of values-based recruitment and how
      to prepare for this type of interview. 

PMID- 25605115
TI  - Cataract management: effect on patients' quality of life.
AB  - This article summarises the epidemiology of cataract, the normal and altered
      physiology of the eye's lens, and the causes of and risk factors associated with
      the condition. It outlines the aims of modern cataract surgery and discusses the
      main surgical approaches. The effects of 'cataract blindness' on the patient's
      quality of life are addressed, with particular reference to the negative effect
      of the onset of depression. The role of the nurse in promoting quality of life is
      explored with reference to the value of psychosocial theory in the care of and
      promotion of health to older patients with cataracts. 

PMID- 25605117
TI  - Suicidal intent.
AB  - In my role as a psychiatric nurse caring for individuals at risk to themselves or
      others, I found the continuing professional development article interesting and
      informative. I have cared for adults, children and young people in a variety of
      settings, including emergency departments, acute care wards and mental health
      hospitals. All of the general hospitals where I work have mental health liaison
      teams that assess each individual's mental health presentation and develop a plan
      of action. 

PMID- 25605116
TI  - Advance care planning in progressive neurological conditions.
AB  - Advance care planning in progressive neurological conditions is an essential part
      of care, allowing individuals to make decisions and record their wishes regarding
      the care they receive in the future. Nurses are ideally placed to become involved
      in this process and should understand how they can assist patients, carers and
      families through a dynamic process of consultation and discussion. This article
      considers the process of advance care planning in relation to progressive
      neurological conditions and discusses how the Mental Capacity Act 2005 provides
      the legislation within which professionals must work. 

PMID- 25605118
TI  - Leading by example.
AB  - Winning the Inspiring Leader of the Year award from independent provider Care UK,
      which delivers health care in several UK prisons, was a career high point for
      John Tsikata. 

PMID- 25605119
TI  - 'A whole world of opportunity'.
AB  - Last year, NHS England announced that 74 trusts had been awarded a total of
      around L30 million from the Nursing Technology Fund. This is for projects to
      support nurses, midwives and health visitors make better use of digital
      technology for safer, more effective and efficient care. 

PMID- 25605121
TI  - Broadening horizons.
AB  - A nursing professor is funding a travel scholarship to help nurses in Wales
      increase their understanding of practice in other parts of the world. 

PMID- 25605122
TI  - Student life--Acting out scenarios.
AB  - The University of the West of Scotland's school of health nursing and midwifery
      has been recognised in the Scottish Clinical Skills Strategy as a higher
      education institution that provides effective clinical skills training to pre
      registration nursing students. 

PMID- 25605123
TI  - Image-based quantification and mathematical modeling of spatial heterogeneity in
      ESC colonies.
AB  - Pluripotent embryonic stem cells (ESCs) have the potential to differentiate into
      cells of all three germ layers. This unique property has been extensively studied
      on the intracellular, transcriptional level. However, ESCs typically form
      clusters of cells with distinct size and shape, and establish spatial structures
      that are vital for the maintenance of pluripotency. Even though it is recognized
      that the cells' arrangement and local interactions play a role in fate decision
      processes, the relations between transcriptional and spatial patterns have not
      yet been studied. We present a systems biology approach which combines live-cell
      imaging, quantitative image analysis, and multiscale, mathematical modeling of
      ESC growth. In particular, we develop quantitative measures of the morphology and
      of the spatial clustering of ESCs with different expression levels and apply them
      to images of both in vitro and in silico cultures. Using the same measures, we
      are able to compare model scenarios with different assumptions on cell-cell
      adhesions and intercellular feedback mechanisms directly with experimental data.
      Applying our methodology to microscopy images of cultured ESCs, we demonstrate
      that the emerging colonies are highly variable regarding both morphological and
      spatial fluorescence patterns. Moreover, we can show that most ESC colonies
      contain only one cluster of cells with high self-renewing capacity. These cells
      are preferentially located in the interior of a colony structure. The integrated
      approach combining image analysis with mathematical modeling allows us to reveal
      potential transcription factor related cellular and intercellular mechanisms
      behind the emergence of observed patterns that cannot be derived from images
      directly.

PMID- 25605124
TI  - Group size effect on cooperation in one-shot social dilemmas.
AB  - Social dilemmas are central to human society. Depletion of natural resources,
      climate protection, security of energy supply, and workplace collaborations are
      all examples of social dilemmas. Since cooperative behaviour in a social dilemma
      is individually costly, Nash equilibrium predicts that humans should not
      cooperate. Yet experimental studies show that people do cooperate even in
      anonymous one-shot interactions. In spite of the large number of participants in
      many modern social dilemmas, little is known about the effect of group size on
      cooperation. Does larger group size favour or prevent cooperation? We address
      this problem both experimentally and theoretically. Experimentally, we find that
      there is no general answer: it depends on the strategic situation. Specifically,
      we find that larger groups are more cooperative in the Public Goods game, but
      less cooperative in the N-person Prisoner's dilemma. Theoretically, we show that
      this behaviour is not consistent with either the Fehr &Schmidt model or (a one
      parameter version of) the Charness &Rabin model, but it is consistent with the
      cooperative equilibrium model introduced by the second author. 

PMID- 25605125
TI  - [Contribution of patients to the improvement of quality in the healthcare
      system].

PMID- 25605127
TI  - Neonatal hydrocortisone therapy does not have a serious suppressive effect on the
      later function of the hypothalamus-pituitary-adrenal axis.
AB  - AIM: This study investigated whether providing extremely low birthweight (ELBW)
      infants with a large amount of hydrocortisone had a serious suppressive effect on
      the later function of the hypothalamus-pituitary-adrenal (HPA) axis. METHODS: We
      evaluated the function of the HPA axis in 58 ELBW infants receiving 9.0 +/- 7.2
      mg/kg of intravenous and 68.1 +/- 34.1 mg/kg of oral hydrocortisone using a human
      corticotropin-releasing hormone stimulation test. The mean age at investigation
      was 12.0 +/- 5.2 months. The response was judged to be normal when the maximum to
      minimum ratio of the plasma adrenocorticotropic hormone (ACTH) concentration was
      >2, the peak value of the serum cortisol concentration was >552 nmol/L, or the
      increment was >193 nmol/L than baseline concentration. RESULTS: Of the 58 infants
      studied, 51 (88%) displayed a normal response to both the ACTH and cortisol
      secretion and seven infants (12%) who were judged to be poor responders exhibited
      a peak cortisol value of >386 nmol/L without any episode of adrenal
      insufficiency. CONCLUSION: Providing ELBW infants with a daily low dose of long
      term hydrocortisone therapy should not lead to a serious suppressive effect on
      the later function of the HPA axis, regardless of the administration method.

PMID- 25605126
TI  - Impaired corrective responses to postural perturbations of the arm in individuals
      with subacute stroke.
AB  - BACKGROUND: Stroke is known to alter muscle stretch responses following a
      perturbation, but little is known about the behavioural consequences of these
      altered feedback responses. Characterizing impairments in people with stroke in
      their interactions with the external environment may lead to better long term
      outcomes. This information can inform therapists about rehabilitation targets and
      help subjects with stroke avoid injury when moving in the world. METHODS: In this
      study, we developed a postural perturbation task to quantity upper limb function
      of subjects with subacute stroke (n = 38) and non-disabled controls (n = 74) to
      make rapid corrective responses with the arm. Subjects were instructed to
      maintain their hand at a target before and after a mechanical load was applied to
      the limb. Visual feedback of the hand was removed for half of the trials at
      perturbation onset. A number of parameters quantified subject performance, and
      impairment in performance was defined as outside the 95th percentile performance
      of control subjects. RESULTS: Individual subjects with stroke showed increased
      postural instability (44%), delayed motor responses (79%), delayed returns
      towards the spatial target (79%), and greater endpoint errors (74%). Several
      subjects also showed impairments in the temporal coordination of the elbow and
      shoulder joints when responding to the perturbation (47%). Interestingly,
      impairments in task parameters were often found for both arms of individual
      subjects with stroke (up to 58% for return time). Visual feedback did not improve
      performance on task parameters except for decreasing endpoint error for all
      subjects. Significant correlations between task performance and clinical measures
      were dependent on the arm assessed. CONCLUSIONS: This study used a simple
      postural perturbation task to highlight that subjects with stroke commonly have
      difficulties responding to mechanical disturbances that may have important
      implications for their ability to perform daily activities.

PMID- 25605130
TI  - Is it time to integrate patient blood management in ERAS guidelines?

PMID- 25605128
TI  - Development of the follicular basement membrane during human gametogenesis and
      early folliculogenesis.
AB  - BACKGROUND: In society, there is a clear need to improve the success rate of
      techniques to restore fertility. Therefore a deeper knowledge of the dynamics of
      the complex molecular environment that regulates human gametogenesis and (early)
      folliculogenesis in vivo is necessary. Here, we have studied these processes
      focusing on the formation of the follicular basement membrane (BM) in vivo.
      RESULTS: The distribution of the main components of the extracellular matrix
      (ECM) collagen IV, laminin and fibronectin by week 10 of gestation (W10) in the
      ovarian cortex revealed the existence of ovarian cords and of a distinct
      mesenchymal compartment, resembling the organization in the male gonads. By W17,
      the first primordial follicles were assembled individually in that (cortical)
      mesenchymal compartment and were already encapsulated by a BM of collagen IV and
      laminin, but not fibronectin. In adults, in the primary and secondary follicles,
      collagen IV, laminin and to a lesser extent fibronectin were prominent in the
      follicular BM. CONCLUSIONS: The ECM-molecular niche compartimentalizes the female
      gonads from the time of germ cell colonization until adulthood. This knowledge
      may contribute to improve methods to recreate the environment needed for
      successful folliculogenesis in vitro and that would benefit a large number of
      infertility patients.

PMID- 25605129
TI  - Anti-obesity and anti-hyperglycemic effects of cinnamaldehyde via altered ghrelin
      secretion and functional impact on food intake and gastric emptying.
AB  - Cinnamon extract is associated to different health benefits but the active
      ingredients or pathways are unknown. Cinnamaldehyde (CIN) imparts the
      characteristic flavor to cinnamon and is known to be the main agonist of
      transient receptor potential-ankyrin receptor 1 (TRPA1). Here, expression of
      TRPA1 in epithelial mouse stomach cells is described. After receiving a single
      dose of CIN, mice significantly reduce cumulative food intake and gastric
      emptying rates. Co-localization of TRPA1 and ghrelin in enteroendocrine cells of
      the duodenum is observed both in vivo and in the MGN3-1 cell line, a ghrelin
      secreting cell model, where incubation with CIN up-regulates expression of TRPA1
      and Insulin receptor genes. Ghrelin secreted in the culture medium was quantified
      following CIN stimulation and we observe that octanoyl and total ghrelin are
      significantly lower than in control conditions. Additionally, obese mice fed for
      five weeks with CIN-containing diet significantly reduce their cumulative body
      weight gain and improve glucose tolerance without detectable modification of
      insulin secretion. Finally, in adipose tissue up-regulation of genes related to
      fatty acid oxidation was observed. Taken together, the results confirm anti
      hyperglycemic and anti-obesity effects of CIN opening a new approach to
      investigate how certain spice derived compounds regulate endogenous ghrelin
      release for therapeutic intervention. 

PMID- 25605131
TI  - Headache yesterday in Russia: its prevalence and impact, and their application in
      estimating the national burden attributable to headache disorders.
AB  - BACKGROUND: Evaluation of the prevalence and impact of headache on the preceding
      day ("headache yesterday"; HY) is a new approach, allowing more precise
      estimation of headache-attributed burden without recall error. The aim of the
      study was to estimate the national burden attributable to headache disorders in
      Russia by applying measures of prevalence of HY and its impact on productivity
      and daily activities in the general population. METHODS: We interviewed a
      representative population-based sample face-to-face by visiting randomly selected
      households throughout Russia. We randomly selected one adult aged 18-65 years
      from each. We followed a structured questionnaire including diagnostic questions,
      enquiry into occurrence of HY and various aspects of attributed burden. RESULTS:
      Participation rate was 74.3%. One in seven participants (14.5%; men 9.1%: women
      19.3%) reported HY. Approximately half of these had one of the subtypes of
      headache occurring on >=15 days/month; the remainder had episodic migraine or
      tension-type headache almost equally. Mean duration of headache was 6.0 +/- 4.4
      hours. In 88.3% headache intensity was moderate or severe (mean 2.1 on a scale 1
      3) and in 73.9% HY impaired daily activity. Loss of productivity at work due to
      headache totalled 2.6 million person-years/year, or 4.0% of workforce capacity.
      This estimate exceeded by 70% a previous estimate from the same survey based on
      recall over the preceding 3 months. There was greater impact on other daily
      activities. CONCLUSION: Recall-error-free estimation shows lost productivity
      every day due to headache in the Russian population is enormously high. Measures
      to redress these losses - effective structured health-care services supported by
      educational programmes - should be seen as a public-health priority while almost
      certainly being cost-saving.

PMID- 25605132
TI  - A triphenyl amine-based solvatofluorochromic dye for the selective and
      ratiometric sensing of OCl- in human blood cells.
AB  - A new visible-light-excitable fluorescence ratiometric probe for OCl(-) has been
      developed based on a triphenylamine-diamiomaleonitrile (TAM) moiety. The
      structure of the dye was confirmed by single-crystal X-ray analysis. It behaves
      as a highly selective and sensitive probe for OCl(-) over other analytes with a
      fast response time (~100 s). OCl(-) reacts with the probe leading to the
      formation of the corresponding aldehyde in a mixed-aqueous system. The detection
      limit of the probe is in the 10(-8) M range. The probe (TAM) also exhibits
      solvatofluorochromism. Changing the solvent from non-polar to polar, the emission
      band of TAM largely red-shifted. Moreover, the probe shows an excellent
      performance in real-life application in detecting OCl(-) in human blood cells.
      The experimentally observed changes in the structure and electronic properties of
      the probe after reaction with OCl(-) were studied by DFT and TDDFT computational
      calculations.

PMID- 25605133
TI  - Modelling DW-MRI data from primary and metastatic ovarian tumours.
AB  - OBJECTIVES: To assess goodness-of-fit and repeatability of mono-exponential,
      stretched exponential and bi-exponential models of diffusion-weighted MRI (DW
      MRI) data in primary and metastatic ovarian cancer. METHODS: Thirty-nine primary
      and metastatic lesions from thirty-one patients with stage III or IV ovarian
      cancer were examined before and after chemotherapy using DW-MRI with ten
      diffusion-weightings. The data were fitted with (a) a mono-exponential model to
      give the apparent diffusion coefficient (ADC), (b) a stretched exponential model
      to give the distributed diffusion coefficient (DDC) and stretching parameter
      (alpha), and (c) a bi-exponential model to give the diffusion coefficient (D),
      perfusion fraction (f) and pseudodiffusion coefficient (D*). RESULTS:
      Coefficients of variation, established from repeated baseline measurements, were:
      ADC 3.1%, DDC 4.3%, alpha 7.0%, D 13.2%, f 44.0%, D* 165.1%. The bi-exponential
      model was unsuitable in these data owing to poor repeatability. After excluding
      the bi-exponential model, analysis using Akaike Information Criteria showed that
      the stretched exponential model provided the better fit to the majority of pixels
      in 64% of lesions. CONCLUSIONS: The stretched exponential model provides the
      optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph
      nodes in pre-treatment and post-treatment measurements with good repeatability.
      KEY POINTS: * DW-MRI data in ovarian cancer show deviation from mono-exponential
      behaviour * Parameters derived from the stretched exponential model showed good
      repeatability (CV 7%) * The bi-exponential model was unsuitable because of poor
      parameter repeatability * The stretched exponential model showed comparable
      repeatability to the mono-exponential model * The extra parameter (alpha)
      provides scope for investigation of heterogeneity or response.

PMID- 25605134
TI  - A small lytic polysaccharide monooxygenase from Streptomyces griseus targeting
      alpha- and beta-chitin.
AB  - The lytic polysaccharide monooxygenases (LPMOs) have received considerable
      attention subsequent to their discovery because of their ability to boost the
      enzymatic conversion of recalcitrant polysaccharides. In the present study, we
      describe the enzymatic properties of SgLPMO10F, a small (15 kDa) auxilliary
      activity (AA) family 10 LPMO from Streptomyces griseus belonging to a clade of
      the phylogenetic tree without any characterized representative. The protein was
      expressed using a Brevibacillus-based expression system that had not been used
      previously for LPMO expression and that also ensures correct processing of the N
      terminus crucial for LPMO activity. The enzyme was active towards both alpha- and
      beta-chitin and showed stronger binding and a greater release of soluble oxidized
      products for the latter allomorph. In chitinase synergy assays, however,
      SgLPMO10F worked slightly better for alpha-chitin, increasing chitin
      solubilization yields by up to 30-fold and 20-fold for alpha- and beta-chitin,
      respectively. Synergy experiments with various chitinases showed that the
      addition of SgLPMO10F leads to a substantial increase in the (GlcNAc)2 :GlcNAc
      product ratio, in reactions with alpha-chitin only. This underpins the structural
      differences between the substrates and also shows that, on alpha-chitin,
      SgLPMO10F affects the binding mode and/or degree of processivity of the
      chitinases tested. Variation in the only exposed aromatic residue in the
      substrate-binding surface of LPMO10s has previously been linked to preferential
      binding for alpha-chitin (exposed Trp) or beta-chitin (exposed Tyr). Mutation of
      this residue, Tyr56, in SgLPMO10F to Trp had no detectable effect on substrate
      binding preferences but, in synergy experiments, the mutant appeared to be more
      efficient on alpha-chitin. 

PMID- 25605135
TI  - A complex perovskite-type oxynitride: the first photocatalyst for water splitting
      operable at up to 600 nm.
AB  - One of the simplest methods for splitting water into H2 and O2 with solar energy
      entails the use of a particulate-type semiconductor photocatalyst. To harness
      solar energy efficiently, a new water-splitting photocatalyst that is active over
      a wider range of the visible spectrum has been developed. In particular, a
      complex perovskite-type oxynitride, LaMg(x)Ta(1-x)O(1+3x)N(2-3x)(x>=1/3), can be
      employed for overall water splitting at wavelengths of up to 600 nm. Two
      effective strategies for overall water splitting were developed. The first
      entails the compositional fine-tuning of a photocatalyst to adjust the bandgap
      energy and position by forming a series of LaMg(x)Ta(1-x)O(1+3x)N(2-3x) solid
      solutions. The second method is based on the surface coating of the photocatalyst
      with a layer of amorphous oxyhydroxide to control the surface redox reactions. By
      combining these two strategies, the degradation of the photocatalyst and the
      reverse reaction could be prevented, resulting in successful overall water
      splitting.

PMID- 25605136
TI  - The association between social position and self-rated health in 10 deprived
      neighbourhoods.
AB  - BACKGROUND: A number of studies have shown that poor self-rated health is more
      prevalent among people in poor, socially disadvantaged positions. The aim of the
      present study was to investigate the association between self-rated health and
      social position in 10 deprived neighbourhoods. METHODS: A stratified random
      sample of 7,934 households was selected. Of these, 641 were excluded from the
      study because the residents had moved, died, or were otherwise unavailable. Of
      the net sample of 7,293 individuals, 1,464 refused to participate, 885 were not
      at home, and 373 did not participate for other reasons, resulting in an average
      response rate of 62.7%. Multiple logistic regression models were used to estimate
      the associations between the number of life resources and the odds of self-rated
      health and also between the type of neighbourhood and the odds of self-rated
      health. RESULTS: The analysis shows that the number of life resources is
      significantly associated with having poor/very poor self-rated health for both
      genders. The results clearly suggest that the more life resources that an
      individual has, the lower the risk is of that individual reporting poor/very poor
      health. CONCLUSIONS: The results show a strong association between residents'
      number of life resources and their self-rated health. In particular, residents in
      deprived rural neighbourhoods have much better self-rated health than do
      residents in deprived urban neighbourhoods, but further studies are needed to
      explain these urban/rural differences and to determine how they influence health.

PMID- 25605137
TI  - Effects of co-culture of cumulus oocyte complexes with denuded oocytes during in
      vitro maturation on the developmental competence of cloned bovine embryos.
AB  - This study evaluated the effects of co-culture of immature cumulus oocyte
      complexes (COCs) with denuded immature oocytes (DO) during in vitro maturation on
      the developmental competence and quality of cloned bovine embryos. We
      demonstrated that developmental competence, judged by the blastocyst formation
      rate, was significantly higher in the co-cultured somatic cell nuclear transfer
      (SCNT+DO, 37.1 +/- 1.1%) group than that in the non-co-cultured somatic cell
      nuclear transfer (SCNT-DO, 25.1 +/- 0.9%) group and was very similar to that in
      the control IVF (IVF, 38.8 +/- 2.8%) group. Moreover, the total cell number per
      blastocyst in the SCNT+DO group (101.7 +/- 6.2) was higher than that in the SCNT
      DO group (81.7 +/- 4.3), while still less than that in the IVF group (133.3 +/-
      6.0). Furthermore, our data showed that mRNA levels of the methylation-related
      genes DNMT1 and DNMT3a in the SCNT+DO group were similar to that in the IVF
      group, while they were significantly higher in the SCNT-DO group. Similarly,
      while the mRNA levels of the deacetylation-related genes HDAC2 and HDAC3 were
      significantly higher in the SCNT-DO group, they were comparable between the IVF
      and SCNT+DO groups. However, the mRNA levels of HDAC1 and DNMT3B were
      significantly higher in the SCNT+DO group than in the other groups. In
      conclusion, the present study demonstrated that co-culture of COCs with DO
      improves the in vitro developmental competence and quality of cloned embryos, as
      evidenced by increased total cell number.

PMID- 25605138
TI  - Lifestyle components and primary breast cancer prevention.
AB  - Breast cancer primary prevention is a high research priority due to the high
      psychological and economic costs. The disease is a multistep process and several
      risk factors have been recognized. Over the past three decades numerous studies
      have investigated the association of lifestyle with breast cancer, showing
      independent effects of various factors. We report here a summary of the present
      state of knowledge on the role of lifestyle patterns, such as physical activity,
      diet, smoking, hormone therapy, and experience of psychological stress in the
      modulation of breast cancer in women, and discuss commonly accepted biological
      mechanisms hypothesized as responsible for the associations. The findings
      indicate that regular physical activity of moderate to vigorous intensity is
      probably linked with the decreased breast cancer risk among postmenopausal
      females and suggestive for a decrease of the risk in premenopausal women. In
      contrast, the consumption of high-fat diet, alcohol intake, and use of combined
      estrogen and synthetic progestagen hormonal therapy may increase the risk.
      Epidemiological findings dealing with a role of smoking and experience of
      psychological stress are conflicting. 

PMID- 25605139
TI  - Autophagy-associated targeting pathways of natural products during cancer
      treatment.
AB  - It is well known that conventional chemotherapy and radiation therapy can result
      in toxicity to both normal cells and tumor cells, which causes limitations in the
      application of these therapeutic strategies for cancer control. Novel and
      effective therapeutic strategies for cancers with no or low toxicity for normal
      cells are a high priority. Therefore, natural products with anticancer activity
      have gained more and more attention due to their favorable safety and efficacy
      profiles. Pre-clinical and clinical studies have demonstrated that several
      representative natural compounds such as resveratrol, epigallocatechin-3-gallate,
      curcumin, allicin and ginsenosides have obvious anticancer potential. In this
      article, we summarize autophagy-associated targeting pathways of such natural
      products for inducing the death of cancer cells, and discuss the core autophagic
      pathways involved in cancer treatments. Recent advances in the discovery,
      evaluation and exploitation of natural compounds as therapeutic agents for
      cancers will provide references and support in pre-clinical and clinical
      application of novel natural drugs for the treatment of primary and metastatic
      tumors in the future. 

PMID- 25605140
TI  - Gastric cancer in asian american populations: a neglected health disparity.
AB  - Gastric cancer incidence rates vary dramatically by world region with East Asia
      having the highest rate. The Asian population of the United States (US) is
      growing rapidly and over 17 million Americans are of Asian descent. A majority of
      Chinese, Korean and Vietnamese Americans are immigrants. Americans of East and
      Southeast Asian descent experience marked gastric cancer disparities and the
      incidence rate among Korean men in the US is over five times higher than the
      incidence rate among non-Hispanic white men. Randomized controlled trials have
      provided evidence for the effectiveness of helicobacter pylori identification and
      eradication in preventing gastric cancer. Additionally, Japan and South Korea
      have both experienced improvements in gastric cancer mortality following the
      implementation of programs to detect early stage gastric cancers. There are
      currently no clear US guidelines regarding the primary and secondary prevention
      of gastric cancer in high-risk immigrant populations. However, it is likely that
      a proportion of US physicians are already recommending gastric cancer screening
      for Asian patients and some Asian immigrants to the US may be completing
      screening for gastric cancer in their native countries. Surveys of US primary
      care physicians and Asian American communities should be conducted to assess
      current provider practices and patient uptake with respect to gastric cancer
      prevention and control. In the absence of clinical guidelines, US health care
      providers who serve high-risk Asian groups could consider a shared decision
      making approach to helicobacter pylori identification and eradication, as well as
      gastric endoscopy. 

PMID- 25605141
TI  - A novel model for smart breast cancer detection in thermogram images.
AB  - BACKGROUND: Accuracy in feature extraction is an important factor in image
      classification and retrieval. In this paper, a breast tissue density
      classification and image retrieval model is introduced for breast cancer
      detection based on thermographic images. The new method of thermographic image
      analysis for automated detection of high tumor risk areas, based on two
      directional two-dimensional principal component analysis technique for feature
      extraction, and a support vector machine for thermographic image retrievalwas
      tested on 400 images. The sensitivity and specificity of the model are 100% and
      98%, respectively.

PMID- 25605142
TI  - Clinicopathological characteristics of triple negative breast cancer at a
      tertiary care hospital in India.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC), characterized by the lack of
      expression of estrogen receptor, progesterone receptor and human epidermal growth
      factor receptor-2, is typically associated with a poor prognosis. The majority of
      TNBCs show the expression of basal markers on gene expression profiling and most
      authors accept TNBC as basal-like (BL) breast cancer. However, a smaller fraction
      lacks a BL phenotype despite being TNBC. The literature is silent on non-basal
      like (NBL) type of TNBC. The present study was aimed at defining behavioral
      differences between BL and NBL phenotypes. OBJECTIVES: i) Identify the TNBCs and
      categorize them into BL and NBL breast cancer. ii) Examine the behavioral
      differences between two subtypes. iii) Observe the pattern of treatment failure
      among TNBCs. MATERIALS AND METHODS: All TNBC cases during January 2009-December
      2010 were retrieved. The subjects fitting the inclusion criteria of study were
      differentiated into BL and NBL phenotypes using surrogate immunohistochemistry
      with three basal markers 34betaE12, c-Kit and EGFR as per the algorithm defined
      by Nielsen et al. The detailed data of subjects were collated from clinical
      records. The comparison of clinicopathological features between two subgroups was
      done using statistical analyses. The pattern of treatment failure along with its
      association with prognostic factors was assessed. RESULTS: TNBC constituted 18%
      of breast cancer cases considered in the study. The BL and NBL subtypes accounted
      for 81% and 19% respectively of the TNBC group. No statistically significant
      association was seen between prognostic parameters and two phenotypes. Among
      patients with treatment failure, 19% were with BL and 15% were with NBL
      phenotype. The mean disease free survival (DFS) in groups BL and NBL was 30.0 and
      37.9 months respectively, while mean overall survival (OS) was 31.93 and 38.5
      months respectively. Treatment failure was significantly associated with stage
      (p=.023) among prognostic factors. CONCLUSIONS: Disease stage at presentation is
      an important prognostic factor influencing the treatment failure and survival
      among TNBCs. Increasing tumor size is related to lymph node positivity. BL tumors
      have a more aggressive clinical course than that of NBL as shown by shorter DFS
      and OS, despite having no statistically significant difference between prognostic
      parameters. New therapeutic alternatives should be explored for patients with
      this subtype of breast cancer.

PMID- 25605143
TI  - Clinicopathological significance of BRCA1 promoter hypermethylation in Thai
      breast cancer patients.
AB  - Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is
      implicated in the mechanisms of cellular DNA repair. Inactivation of this gene is
      involved in the development of many human cancers, including breast cancer. This
      study aimed to investigate the prognostic value of BRCA1 promoter
      hypermethylation and expression in breast cancer cases. Sixty-one breast cancers
      were examined for BRCA1 hypermethylation by methylation-specific polymerase chain
      reaction (PCR), and 45 paired normal breast tissues were analyzed for altered
      BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase
      chain reaction (qRT- PCR). Aberrant methylation status in BRCA1 was detected in
      15 of 61 cases (24.6%), while reduced expression was found in 7 of 45 (15.6%).
      BRCA1 hypermethylation was statistically associated with tumor grade III
      (p=0.04), a high frequency of stage IIB (p=0.02), and triple-negative phenotype
      (OR= 3.64, 95%CI =1.1-12.3, p=0.03). Our findings indicated that BRCA1 promoter
      hypermethylation is a useful prognostic marker for breast cancer. 

PMID- 25605145
TI  - RNAi-based knockdown of multidrug resistance-associated protein 1 is sufficient
      to reverse multidrug resistance of human lung cells.
AB  - Up-regulation of multidrug resistance-associated protein 1 (MRP1) is regarded as
      one of the main causes for multidrug resistance (MDR) of tumor cells, leading to
      failure of chemotherapy-based treatment for a multitude of cancers. However,
      whether silencing the overexpressed MRP1 is sufficient to reverse MDR has yet to
      be validated. This study demonstrated that RNAi-based knockdown of MRP1 reversed
      the increased efflux ability and MDR efficiently. Two different short haipin RNAs
      (shRNAs) targeting MRP1 were designed and inserted into pSilence- 2.1-neo. The
      shRNA recombinant plasmids were transfected into cis-dichlorodiamineplatinum
      resistant A549 lung (A549/DDP) cells, and then shRNA expressing cell clones were
      collected and maintained. Real time PCR and immunofluorescence staining for MRP1
      revealed a high silent efficiency of these two shRNAs. Functionally, shRNA
      expressing cells showed increased rhodamine 123 retention in A549/DDP cells,
      indicating reduced efflux ability of tumor cells in the absence of MRP1.
      Consistently, MRP1-silent cells exhibited decreased resistance to 3- (4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and DDP, suggesting
      reversal of MDR in these tumor cells. Specifically, MRP1 knockdown increased the
      DDP-induced apoptosis of A549/DDP cells by increased trapping of their cell
      cycling in the G2 stage. Taken together, this study demonstrated that RNAi- based
      silencing of MRP1 is sufficient to reverse MDR in tumor cells, shedding light on
      possible novel clinical treatment of cancers. 

PMID- 25605144
TI  - Expression of tumor necrosis factor receptor-associated factor 6 in lung cancer
      tissues.
AB  - BACKGROUND: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has
      been reported to be associated with the development of various cancers. However,
      the role of TRAF6 in lung cancer remains unclear. OBJECTIVE: To explore the
      expression and clinicopathological significance of TRAF6 protein in lung cancer
      tissues. MATERIALS AND METHODS: Three hundred and sixty-five lung cancer samples
      and thirty normal lung tissues were constructed into 3 microarrays. The
      expression of TRAF6 protein was determined using immunohistochemistry (IHC).
      Furthermore, correlations between the expression of TRAF6 and clinicopathological
      parameters were investigated. RESULTS: The expression of TRAF6 in total lung
      cancer tissues (365 cases), as well as in small cell lung cancer (SCLC, 26 cases)
      and non-small cell lung cancer (NSCLC, 339 cases) was significantly higher
      compared with that in normal lung tissues. The ROC curve showed that the area
      under curve of TRAF6 was 0.663 (95%CI 0.570~0.756) for lung cancer. The
      diagnostic sensitivity and specificity of TRAF6 were 52.6% and 80%, respectively.
      In addition, the expression of TRAF6 was correlated with clinical TNM stage,
      tumor size and lymph node metastasis in all lung cancers. Consistent correlations
      were also observed for NSCLCs. CONCLUSIONS: TRAF6 might be an oncogene and the
      expression of TRAF6 protein is related to the progression of lung cancer. Thus,
      TRAF6 might become a target for diagnosis and gene therapy for lung cancer
      patients.

PMID- 25605146
TI  - Evaluation of environmental risk factors for prostate cancer in a population of
      Iranian patients.
AB  - BACKGROUND: The Prostate cancer is the 2nd most common cancer worldwide for
      males, and the 5th most common cancer overall, with an estimated 900,000 new
      cases diagnosed in 2008 (14% of the total in males and 7% of the total overall)
      aim of this study was to assess some of the most proposed environmental factors
      influencing the incidence of prostate cancer among Iranian men. Smoking, opioids,
      occupation and living location were considered as studied risk factors of the
      prostate cancer in this research. MATERIAL AND METHODS: Two groups of affected
      men with prostate cancer and controls aged 50-75 years referred to medical
      clinics were subjects in this case-control study. Living and working place,
      smoking and drug consuming habits were assessed for any associations with
      prostate cancer. RESULTS: The largest number, of patients, in order, belonged to
      Tehran, provincial capitals, major industrial cities, small towns and villages,
      respectively. The disease showed links with smoking and drugs with a significant
      difference between controls and patients (P value <0.0001). CONCLUSIONS: Our
      recent evidence duplicates previously done researches confirming the serious
      adverse effects of smoking and drugs on the prostate cancer occurrence in Iranian
      men. Living place bearings some hazardous behaviors which increases the rate of
      diseases as well as advanced chance for associated cancers like prostate.

PMID- 25605147
TI  - Is her-2 status in the primary tumor correlated with matched lymph node
      metastases in patients with gastric cancer undergoing curative gastrectomy?
AB  - BACKGROUND: HER2 expression in the primary tumor and its lymph node metastases
      vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also
      suggests that proliferation of a different clone in metastatic nodes is possible.
      In the current study, we aimed to determine the cause of discordance in HER-2
      expression in the primary tumor and lymph node metastases for patients with
      gastric cancer. MATERIALS AND METHODS: Eighty-one patients with gastric cancer
      who had undergone radical gastrectomy and were found to have lymph node
      metastasis upon pathological examination were included. Histopathological samples
      were obtained from biopsies obtained during patient gastrectomies and lymph node
      dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and
      silver in situ hybridization (SISH). RESULTS: Sixty-four (79%) patients were SISH
      (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic
      lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-)
      primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in
      the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors
      and lymph node metastases were comparable, showing a concordance of 92.5%. In
      total, six patients demonstrated discordance between the primary tumor and lymph
      node metastases. The prevalence of HER2 discordance was significantly higher for
      patients in the pN2 and N3 stages (p=0.007). Although discordant patients had
      worse survival rates than concordant patients, the differences were not
      significant (p>0.05). CONCLUSIONS: Our study indicates that the frequency of
      concordance in HER2 status, as determined by IHC or SISH, is high in primary
      tumors and their corresponding lymph node metastases for patients with gastric
      cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and
      SISH may be useful for detecting patients who would benefit from trastuzumab, and
      it would therefore help guide decision-making processes in administering
      treatment.

PMID- 25605148
TI  - Ethanol but not aqueous extracts of tubers of Sauromatum Giganteum(Engl.)
      Cusimano and Hett inhibit cancer cell proliferation.
AB  - BACKGROUND: Both alcohol and aqueous extracts of Sauromatum giganteum(Engl.)
      Cusimano and Hett, the dried root tuber of which is named Baifuzi in Chinese,
      have been used for folklore treatment of cancer in Northeast of China. However,
      little is known about which is most suitable to the cancer therapy. MATERIALS AND
      METHODS: Serum pharmacology and MTT assays were adopted to detect the effects of
      ethanol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett ,
      prepared by heat reflux methods, on proliferation of different cancer cells.
      RESULTS: Cancer cells treated with medium supplemented with 10%, 20%, 40%
      serum(v/v) containing ethanol extract had a decline in viability, with inhibition
      rates of 7.69%, 21.8%, 41.9% in MCF-7 cells, 42.8%, 48.1%, 51.8% in SGC-7901
      cells, 44.1%, 49.2%, 53.7% in SMMC-7721 cells, 6.8%, 15.2%, 39.8% in HepG2 cells,
      7.57%, 16.3%, 36.2% in HeLa cells, 6.24%, 12.5%, 27.4% in A549 cells, and 7.20%,
      17.5%, 31.3% in MDA-MB-231 cells, respectively. Viability in the aqueous extract
      groups was no different with that of controls. CONCLUSIONS: An ethanol extract of
      Sauromatum giganteum(Engl.) Cusimano and Hett inhibited the proliferation of SMMC
      7721, SGC-7901 and MCF-7 cells, which supports the use of alcoholic but not
      aqueous extracts for control of sensive cancers, which might include
      hepatocarcinoma, gastric cancer and breast cancer.

PMID- 25605149
TI  - High expression of forkhead box protein C2 is related to poor prognosis in human
      gliomas.
AB  - BACKGROUND: Increasing evidence has indicated that high Forkhead box protein C2
      (FOXC2) level is closely associated with the development, progression, and poor
      prognosis of a variety of tumors. However, the relationship between FOXC2 and the
      progression of human gliomas remains to be clarified. The aim of present study
      was to assess FOXC2 expression and to explore its contribution in human gliomas.
      MATERIALS AND METHODS: Realtime quantitative PCR was performed to examine FOXC2
      expression in 85 pairs of fresh frozen glioma tissues and corresponding non
      neoplastic brain tissues. Associations of FOXC2 expression with
      clinicopathological factors and prognosis of glioma patients were statistically
      analyzed. RESULTS: The relative mRNA expression of FOXC2 was significantly higher
      in glioma tissues than the corresponding non-neoplastic brain tissues (p<0.001).
      In addition, high FOXC2 expression was significantly associated with advanced
      pathological grade (P=0.005) and the low Karnofsky performance score (KPS)
      (p=0.003), correlating with poor survival (p<0.001). Furthermore, multivariate
      Cox regression analysis showed that high FOXC2 expression was an independent
      predictor of overall survival (p=0.006). CONCLUSIONS: FOXC2 may act as an
      oncogenic gene and represent a potential regulator of aggressive development and
      a candidate prognostic marker in human gliomas.

PMID- 25605150
TI  - Epidermal growth factor receptor mutations in Japanese men with lung
      adenocarcinomas.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations play a vital role
      in the prognosis of patients with lung adenocarcinoma. Such somatic mutations are
      more common in women who are non-smokers with adenocarcinoma and are of Asian
      origin. However, to our knowledge, there are few studies that have focused on
      men. MATERIALS AND METHODS: One hundred and eighty-four consecutive patients (90
      men and 94 women) of resected lung adenocarcinoma were studied retrospectively.
      RESULTS: EGFR mutations were positive in 48.9% and negative (wild type) in 51.1%.
      Overall mutation was significant in women (66.0% vs. 32.2%) compared with men
      (p<0.001). For overall patients, EGFR mutation status was associated with gender,
      pStage, pT status, lepidic dominant histologic subtype, pure or mixed ground
      glass nodule type on computed tomography and smoking status. However, in men,
      EGFR mutation status was only associated with lepidic dominant histologic subtype
      and not the other variables. Interestingly, the Brinkman index of men with mutant
      EGFR also did not differ from that for the wild type (680.0+/-619.3 vs. 813.1+/
      552.1 p=0.1077). CONCLUSIONS: The clinical characteristics of men with lung
      adenocarcinoma related to EGFR mutation are not always similar to that of overall
      patients. Especially we failed to find the relationship between EGFR mutations
      and smoking status in men.

PMID- 25605151
TI  - Depression, anxiety and sexual satisfaction in breast cancer patients and their
      partners-Izmir oncology group study.
AB  - BACKGROUND: We aimed to investigate anxiety, depression and sexual satisfaction
      levels and the effects of depression and anxiety upon the sexual satisfaction of
      Turkish breast cancer patients and their partners. MATERIALS AND METHODS: Data
      were collected from one hundred breast cancer patients and their partners, using
      three forms: one covering information about socio-demographic characteristics of
      the patients, the Hospital Anxiety and Depression Scale (HADs) and the Golombok
      Rust Inventory of Sexual Satisfaction (GRISS). RESULTS: The frequencies,
      avoidance and touch subscores were statistically significantly high in the
      patients. Among those with high anxiety scores, the frequency, communication,
      satisfaction, touch, and anorgasmic subscale scores of GRISS were found to be
      significantly high. Among the partners whose anxiety scores were high, only the
      premature ejaculation subscale was statistically significant. It was determined
      that for partners with higher depression scores, the communication, satisfaction,
      avoidance, premature ejaculation and erectile dysfunction subscores of GRISS were
      statistically higher compared to partners with lower depression scores.
      CONCLUSIONS: Patients' quality of life may be increased by taking precautions to
      reduce their and their partners' psychosocial and psychosexual concerns.

PMID- 25605152
TI  - How compliant are tobacco vendors to india's tobacco control legislation on Ban
      of advertisments at point of sale? A three jurisdictions review.
AB  - BACKGROUND: Section 5 of India's tobacco control legislation "Cigarettes and
      Other Tobacco Products Act (COTPA), 2003"comprehensively prohibits all kinds of
      tobacco advertisement, promotion and sponsorship (TAPS), but permits
      advertisments at the point-of-sale (POS) under certain conditions. This provision
      has been exploited by the tobacco companies to promote their products. OBJECTIVE:
      To measure compliance with the provisions of Section 5 of Indian tobacco control
      legislation (COTPA, 2003) at point of sale. MATERIALS AND METHODS: A cross
      sectional survey using an observation checklist was conducted in 1860 POS across
      three jurisdictions (Chennai city, District Vadodara and District Mohali) in
      India. RESULTS: The most common mode of advertisement of tobacco products was
      product showcasing (51.1%), followed by dangles (49.6%), stickers (33.8%) and
      boards (27.1%). More than one fourth of POS were found violating legal provisions
      for displaying advertisement boards in one or other forms (oversized, extended to
      full body lenth of POS, displayed brandname/ packshot and promotional messages).
      Advertisement boards (16.3%) without health warnings were also found and wherever
      found, more than 90% health warning were not as per the specification in respect
      to size, font and background color. CONCLUSIONS: Point of sale advertising is
      aggressively used by the tobacco industry to promote their products. There is an
      urgent need of effective implementation of a comprehensive ban on tobacco product
      advertisement, promotion and sponsorship at point of sale.

PMID- 25605153
TI  - Correlation between mammograghic findings and clinical/ pathologic features in
      women with small invasive breast carcinomas.
AB  - BACKGROUND: To study the relationship between mammographic findings and
      clinical/pathologic features in women with 1-15mm sized invasive breast cancer.
      MATERIALS AND METHODS: We investigated a consecutive series of 134 cases
      diagnosed in Tianjin Medical University Cancer Institute and Hospital in 2007.
      Mammographic findings were classified into five groups as follows :1) stellate
      mass without calcification; 2) non-stellate mass without calcification; 3)
      intermediate suspicious calcification with or without associated mass; 4) higher
      probability malignant calcification with or without associated mass; 5) focal
      asymmetry/distortion without associated calcification. Associations between
      mammographic and clinical/pathological features (menopause status/family
      history/histologic grade/lymph node status and ER/PR/HER2 status) was analyzed
      through logistic regression and chi square tests. RESULTS: Compared to the
      stellate mass without calcification group, higher probability malignant
      calcification patients were associated significantly with a positive lymph node
      status, always presenting in patients who were non-menopausal and with a family
      history of carcinoma. CONCLUSIONS: Higher probability malignant calcifications
      with or without associated tumor masses are associated with clinical/pathologic
      features of poor prognosis.

PMID- 25605154
TI  - Co-amplification at lower denaturation-temperature PCR combined with unlabled
      probe high-resolution melting to detect KRAS codon 12 and 13 mutations in plasma
      circulating DNA of pancreatic adenocarcinoma cases.
AB  - BACKGROUND: The aim of our study was to establish COLD-PCR combined with an
      unlabeled-probe HRM approach for detecting KRAS codon 12 and 13 mutations in
      plasma-circulating DNA of pancreatic adenocarcinoma (PA) cases as a novel and
      effective diagnostic technique. MATERIALS AND METHODS: We tested the sensitivity
      and specificity of this approach with dilutions of known mutated cell lines. We
      screened 36 plasma-circulating DNA samples, 24 from the disease control group and
      25 of a healthy group, to be subsequently sequenced to confirm mutations.
      Simultaneously, we tested the specimens using conventional PCR followed by HRM
      and then used target-DNA cloning and sequencing for verification. The ROC and
      respective AUC were calculated for KRAS mutations and/or serum CA 19-9. RESULTS:
      It was found that the sensitivity of Sanger reached 0.5% with COLD- PCR, whereas
      that obtained after conventional PCR did 20%; that of COLD-PCR based on unlabeled
      probe HRM, 0.1%. KRAS mutations were identified in 26 of 36 PA cases (72.2%),
      while none were detected in the disease control and/or healthy group. KRAS
      mutations were identified both in 26 PA tissues and plasma samples. The AUC of
      COLD-PCR based unlabeled probe HRM turned out to be 0.861, which when combined
      with CA 19-9 increased to 0.934. CONCLUSIONS: It was concluded that COLD-PCR with
      unlabeled-probe HRM can be a sensitive and accurate screening technique to detect
      KRAS codon 12 and 13 mutations in plasma-circulating DNA for diagnosing and
      treating PA.

PMID- 25605156
TI  - Effects of rapamycin on cell apoptosis in MCF-7 human breast cancer cells.
AB  - BACKGROUND: Rapamycin is an effective anti-angiogenic drug. However, the mode of
      its action remains unclear. Therefore, in this study, we aimed to elucidate the
      antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using
      MCF-7 breast cancer cells. MATERIALS AND METHODS: MCF-7 cells were plated at a
      density of 15105 cells/well in 6-well plates. After 24h, cells were treated with
      a series of concentrations of rapamycin while only adding DMEM medium with PEG
      for the control regiment and grown at 37oC, 5% CO2 and 95% air for 72h. Trypan
      blue was used to determine the cell viability and proliferation. Untreated and
      rapamycin-treated MCF-7 cells were also examined for morphological changes with
      an inverted-phase contrast microscope. Alteration in cell morphology was
      ascertained, along with a stage in the cell cycle and proliferation. In addition,
      cytotoxicity testing was performed using normal mouse breast mammary pads.
      RESULTS: Our results clearly showed that rapamycin exhibited inhibitory activity
      on MCF-7 cell lines. The IC50 value of rapamycin on the MCF-7 cells was
      determined as 0.4MUg/ml (p<0.05). Direct observation by inverted microscopy
      demonstrated that the MCF-7 cells treated with rapamycin showed characteristic
      features of apoptosis including cell shrinkage, vascularization and autophagy.
      Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle
      showed an increase in the G0G1 phase cell population and a corresponding decrease
      in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%,
      respectively. CONCLUSIONS: This study demonstrated that rapamycin may potentially
      act as an anti-cancer agent via the inhibition of growth with some morphological
      changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase
      and induction of apoptosis in late stage of apoptosis. Further studies are needed
      to further characterize the mode of action of rapamycin as an anti-cancer agent.

PMID- 25605155
TI  - Association of a p53 codon 72 gene polymorphism with environmental factors and
      risk of lung cancer: a case control study in Mizoram and Manipur, a high
      incidence region in North East India.
AB  - BACKGROUND: A very high incidence of lung cancer is observed in Mizoram and
      Manipur, North East India. We conducted a population based case control study to
      establish associations of p53 codon 72 polymorphisms and interactions with
      environmental factors for this high incidence. MATERIAL AND METHODS: A total of
      272 lung cancer cases and 544 controls matched for age (+/-5 years), sex and
      ethnicity were collected and p53 codon 72 polymorphism genotypes were analyzed
      using a polymerase chain based restriction fragment length polymorphism assay. We
      used conditional multiple logistic regression analysis to calculate adjusted odds
      ratios and 95% confidence intervals after adjusting for confounding factors.
      RESULTS: p53 Pro/Pro genotype was significantly associated with increased risk of
      lung cancer in the study population (adjusted OR=2.14, CI=1.35-3.38, p=0.001).
      Interactions of the p53 Pro/Pro genotype with exposure to wood smoke (adjusted
      OR=3.60, CI=1.85-6.98, p<0.001) and cooking oil fumes (adjusted OR=3.27, CI=1.55
      6.87, p=0.002), betel quid chewing (adjusted OR=3.85, CI=1.96- 7.55, p<0.001),
      tobacco smoking (adjusted OR=4.42, CI=2.27-8.63, p<0.001) and alcohol consumption
      (adjusted OR=3.31, CI=1.10-10.03, p=0.034) were significant regarding the
      increased risk of lung cancer in the study population. CONCLUSIONS: The present
      study provided preliminary evidence that a p53 codon 72 polymorphism may effect
      lung cancer risk in the study population, interacting synergistically with
      environmental factors.

PMID- 25605157
TI  - Performance indices of needle biopsy procedures for the assessment of screen
      detected abnormalities in services accredited by BreastScreen Australia.
AB  - BACKGROUND: We wished to analyse patterns of use of needle biopsy procedures by
      BreastScreen Australia (BSA) accredited programs to identify areas for
      improvement. DESIGN: BSA services provided anonymous data regarding percutaneous
      needle biopsy of screen detected lesions assessed between 2005-2009. RESULTS: 12
      services, from 5 of 7 Australian states and territories provided data for 18212
      lesions biopsied. Preoperative diagnosis rates were 96.84% for lesion other than
      microcalcification (LOTM) and 93.21% for microcalcifications. At surgery 97.9%
      impalpable lesions were removed at the first procedure. Of 11548
      Microcalcification (LOTM) biopsied, 46.9% were malignant. The final diagnosis was
      reached by conventional core biopsy (CCB) in 72.46%, FNAB in 21.33%, VACB in
      1.69% and open biopsy in 4.52% of lesions. FNA is being limited to LOTM with
      benign imaging After FNAB, core biopsy was required for 38% of LOTM. In LOTM the
      mean false positive rate (FPR) was 0.36% for FNAB, 0.06% for NCB and 0% for VACB.
      Diagnostic accuracy was 72.75% for FNAB and 92.1% for core biopsies combined. Of
      6441 microcalcifications biopsied 2305 (35.8%) were malignant.
      Microcalcifications are being assessed primarily by NCB but 6.57% underwent FNAB,
      45.6% of which required NCB. False positive diagnoses were rare. FNR was 5% for
      NCB and 1.53% for VACB. Diagnostic accuracy was 73.52% for FNAB, 86.29% for NCB
      and 88.63% for VACB. Only 8 of 12 services had access to VACB facilities.
      CONCLUSIONS: BSA services are selecting lesions effectively for biopsy and are
      achieving high preoperative diagnosis rates. Gaps in the present accreditation
      standards require further consideration.

PMID- 25605158
TI  - Meta-analysis of associations between ATM Asp1853Asn and TP53 Arg72Pro
      polymorphisms and adverse effects of cancer radiotherapy.
AB  - BACKGROUND: The ataxia telangiectasia mutated (ATM) protein and p53 play key
      roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs).
      Accumulating epidemiological evidence indicates that functional genetic variants
      in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side
      effects. Here we performed a meta-analysis to investigate the potential
      interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of
      radiotherapy-induced adverse effects quantitatively. MATERIALS AND METHODS:
      Relevant articles were retrieved from PubMed, ISI Web of Science and the China
      National Knowledge Infrastructure (CNKI) databases. Eligible studies were
      selected according to specific inclusion and exclusion criteria. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association
      between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy
      adverse effects. All analyses were performed using the Stata software. RESULTS: A
      total of twenty articles were included in the present analysis. In the overall
      analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro
      polymorphisms and the risk of radiotherapy adverse effects were found. We
      conducted subgroup analysis stratified by type of cancer, region and time of
      appearance of side effects subsequently. No significant association between ATM
      Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup
      analysis. For TP53 Arg72Pro, variant C allele was associated with decreased
      radiotherapy adverse effects risk among Asian cancer patients in the stratified
      analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results
      were found in the subgroup analysis of tumor type and time of appearance of side
      effects. CONCLUSIONS: The TP53 Arg72Pro C allele might be a protective factor of
      radiotherapy-induced adverse effects among cancer patients from Asia. Further
      studies that take into consideration treatment-related factors and patient
      lifestyle including environmental exposures are warranted.

PMID- 25605159
TI  - Refining and validating a two-stage and web-based cancer risk assessment tool for
      village doctors in China.
AB  - The big gap between efficacy of population level prevention and expectations due
      to heterogeneity and complexity of cancer etiologic factors calls for selective
      yet personalized interventions based on effective risk assessment. This paper
      documents our research protocol aimed at refining and validating a two-stage and
      web- based cancer risk assessment tool, from a tentative one in use by an ongoing
      project, capable of identifying individuals at elevated risk for one or more
      types of the 80% leading cancers in rural China with adequate sensitivity and
      specificity and featuring low cost, easy application and cultural and technical
      sensitivity for farmers and village doctors. The protocol adopted a modified
      population-based case control design using 72, 000 non-patients as controls, 2,
      200 cancer patients as cases, and another 600 patients as cases for external
      validation. Factors taken into account comprised 8 domains including diet and
      nutrition, risk behaviors, family history, precancerous diseases, related medical
      procedures, exposure to environment hazards, mood and feelings, physical
      activities and anthropologic and biologic factors. Modeling stresses explored
      various methodologies like empirical analysis, logistic regression, neuro-network
      analysis, decision theory and both internal and external validation using
      concordance statistics, predictive values, etc.. 

PMID- 25605160
TI  - Interaction of tobacco smoking and chewing with Angiotensin converting enzyme
      (insertion/deletion) gene polymorphisms and risk of lung cancer in a high risk
      area from northeast India.
AB  - BACKGROUND: Association of angiotensin converting enzyme (ACE) gene polymorphisms
      with lung cancer susceptibility remains uncertain and varies with ethnicity.
      Northeast India represents a geographically, culturally, and ethnically isolated
      population. The area reports an especially high rate of tobacco usage in a
      variety of ways of consumption, compared with the rest of the Indian population.
      MATERIALS AND METHODS: We conducted a population based case control study in two
      major high risk region for lung cancer from Northeast India. A total of 151
      consecutive lung cancer cases diagnosed histopathologically and equal numbers of
      controls were recruited with record of relevant sociodemographic information.
      Blood samples were collected and processed to identify ACE gene polymorphism.
      RESULTS: Significantly higher (40.4 % vs 29.1%, OR=1.97, CI=1.04-3.72; p=0.037)
      prevalence of the ACE II genotype was observed among lung cancer cases. Smoking
      was significantly associated with increased risk of lung cancer (OR=1.70, CI=1.02
      2.81; p=0.041). An enhanced risk was also observed for interaction of ACE II
      genotype with tobacco smoking (OR=4.09, CI=1.51-11.05; p=0.005) and chewing
      (OR=3.68, CI=1.22-11.13; p=0.021). CONCLUSIONS: The present study indicates
      significant association s of the ACE II genotype with lung cancer in high risk
      Northeast India.

PMID- 25605161
TI  - Association between laryngeal squamous cell carcinoma and polymorphisms in tumor
      necrosis factor related apoptosis induce ligand (TRAIL), TRAIL receptor and
      sTRAIL levels.
AB  - The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant
      tumors occurring in the head and neck. Tumor necrosis factor related apoptosis
      induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as
      important members of TRAIL-mediated biochemical signaling pathway. Associations
      between polymorphisms in these genes and clinicopathological characteristics of
      human laryngeal carcinoma are not well defined. This study therefore aimed to
      investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms
      and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with
      laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G
      and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels
      were measured by ELISA. There were significant differences in the distribution of
      DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer
      patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased
      frequency of the DR4 C626G homozygote CC genotype in patients than in controls
      (p<0.001). Haplotype analysis revealed that there was also a statistically
      significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal
      cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had
      advanced tumour stage were lower than those of patients with early tumor stage
      (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might
      be associated with progression of laryngeal cancer in the Turkish population. 

PMID- 25605162
TI  - Oral and IV dosages of doxorubicin-methotrexate loaded- nanoparticles inhibit
      progression of oral cancer by down- regulation of matrix Methaloproteinase 2
      expression in vivo.
AB  - Oral cancer is one of the most common and lethal cancers in the world.
      Combination chemotherapy coupled with nanoparticle drug delivery holds
      substantial promise in cancer therapy. This study aimed to evaluate the efficacy
      and safety of two dosages of our novel pH and temperature sensitive doxorubicin
      methotrexate-loaded nanoparticles (DOX-MTX NPs) with attention to the MMP-2 mRNA
      profile in a 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma (OSCC)
      model in the rat. Our results showed that both IV and oral dosages of DOX-MTX NP
      caused significant decrease in mRNA levels of MMP-2 compared to the untreated
      group (p<0.003). Surprisingly, MMP-2 mRNA was not affected in DOX treated
      compared to cancer group (p>0.05). Our results indicated that IV dosage of MTX
      DOX is more effective than free DOX (12 fold) in inhibiting the activity of MMP-2
      in OSCCs (P<0.001). Furthermore, MMP-2 mRNA expression in the DOX-MTX treated
      group showed a significant relation with histopathological changes (P=0.011).
      Compared to the untreated cancer group, we observed no pathological changes and
      neither a significant alteration in MMP-2 amount in either of healthy controls
      that were treated with oral and IV dosages of DOX-MTX NPs whilst cancer group
      showed a high level of MMP-2 expression compared to healthy controls
      (p<0.001).Taking together our results indicate that DOX- MTX NPs is a safe
      chemotherapeutic nanodrug that its oral and IV forms possess potent anti-cancer
      properties on aggressive tumors like OSCC, possibly by affecting the expression
      of genes that drive tumor invasion and metastasis. 

PMID- 25605163
TI  - Serum amyloid A is a novel prognostic biomarker in hepatocellular carcinoma.
AB  - PURPOSE: To investigate the prognostic value of serum amyloid A (SAA) in patients
      with hepatocellular carcinoma (HCC) undergoing surgery. MATERIALS AND METHODS:
      Preoperative serum samples of 328 patients with HCC who underwent curative
      resection and of 47 patients with benign liver lesion were assayed. Serum levels
      of SAA were measured by enzyme-linked immunosorbent assay and its correlations
      with clinicopathological characteristics and survival were explored. RESULTS:
      Levels of SAA were significantly higher in patients with HCC than those with
      benign liver lesion. There were strong correlations between preoperative serum
      SAA level and tumor size and more advanced BCLC stage. On univariate analysis,
      elevated SAA was associated with reduced disease-free survival and overall
      survival (p=0.001 and 0.03, respectively). Multivariate analyses showed that
      serum SAA level was an independent prognostic factor for overall survival (hazard
      ratio 2.80, p=0.01). CONCLUSIONS: High SAA serum level is a novel biomarker for
      the prognosis of HCC patients.

PMID- 25605164
TI  - Common genetic variations in the MUC5AC gene are not related to helicobacter
      pylori serologic status.
AB  - Several lines of evidence suggest that MUC5AC genetic polymorphisms might confer
      susceptibility to H. pylori infection and therefore gastric cancer risk. We here
      assessed the association of common polymorphisms in the MUC5AC gene with H.
      pylori seroprevalence using an LD-based tagSNP approach in a north-western
      Chinese Han population. A total of 12 tagSNPs were successfully genotyped among
      281 unrelated ethnic Han Chinese who had no cancer history, and no identifiable
      gastric disease or genetic disease. No significant association between any
      alleles, genotypes or haplotypes and H. pylori seroprevalence was observed. Our
      results suggest that common genetic variations in MUC5AC gene might not make a
      major contribution to the risk of H. pylori infection. 

PMID- 25605165
TI  - Awareness and attitude relating to the human papilloma virus and its vaccines
      among pediatrics, obstetrics and gynecology specialists in Turkey.
AB  - BACKGROUND: To determine the level of knowledge on human papillomavirus (HPV)
      infection and vaccination, and the attitude towards HPV vaccination in
      pediatricians, obstetricians and gynecologists (OBG). MATERIALS AND METHODS:
      Participants were administered a 40-question survey, investigating the
      demographic properties, the knowledge on the HPV infection-vaccination and
      attitudes towards vaccination. RESULTS: The study enrolled a total of 228
      participants (131 pediatricians and 97 OBGs). At a rate of 99.6%, the
      participants agreed with the fact that the HPV infection was the most common
      sexually transmitted disease and 33.8% of the participants had the opinion that
      the HPV vaccination should be administered only in women. The lowest level of HPV
      vaccine recommendation was among the pediatrics specialists (59.4%, p=0.012).
      When asked whether they would have their daughters receive HPV vaccination, 79.5%
      of the participants answered favorably; this rate was 36.7% for the sons. At a
      rate of 59.5% of the participants thought that the HPV vaccine needed to be
      included in the national vaccine schedule. Most of the participants (91.6%) had
      the idea that reduction of the vaccine costs would increase the vaccination
      frequency. CONCLUSIONS: We observed that the consideration of the costs and the
      prejudices relating to the inefficacy of vaccination as well as the inadequate
      level of knowledge were involved in the physicians' resistance to HPV
      vaccination. We believe that the healthcare professionals should be informed
      adequately to overcome false beliefs, thereby ensuring success of the HPV vaccine
      upon inclusion in the national vaccine schedule in the future.

PMID- 25605166
TI  - Risk factors for clinical metastasis in men undergoing radical prostatectomy and
      immediate adjuvant androgen deprivation therapy.
AB  - BACKGROUND: Adjuvant androgen deprivation therapy (ADT) is a treatment option for
      prostate cancer (PC) patients after radical prostatectomy (RP). Although it can
      achieve a good progression-free survival rate, some patients still develop
      clinical metastasis. We here investigated risk factors of clinical metastasis in
      post- prostatectomy patients who received immediate adjuvant ADT. MATERIALS AND
      METHODS: We identified 197 patients with non-metastatic PC who underwent RP at
      our institution between 2000 and 2012, followed by adjuvant ADT. The associations
      of various clinicopathologic factors with clinical metastasis (primary endpoint)
      and cancer-specific survival (secondary endpoint) were assessed. Multivariate
      analysis was conducted using a Cox proportional hazards model. Median follow-up
      was 87 months after RP. RESULTS: Nine (4.6%) patients developed clinical
      metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a
      pathologic Gleason score (GS) 9 and developed bone metastasis, while the
      remaining one had pathologic GS 7 and developed metastasis only to para-aortic
      lymph nodes. On multivariate analyses, pathologic GS >=9 and regional lymph node
      metastasis (pN1) were independent predictors of clinical metastasis and
      pathologic GS >=9 was an independent predictor of cancer-specific death.
      CONCLUSIONS: Pathologic GS >=9 and pN1 were independent predictors of clinical
      metastasis in post-prostatectomy patients who received immediate adjuvant ADT.
      Furthermore, pathologic GS >=9 was an indispensable condition for bone
      metastasis, which may imply that patients with GS <=8 on adjuvant ADT are
      unlikely to develop bone metastasis.

PMID- 25605168
TI  - Elastography for breast cancer diagnosis: a useful tool for small and BI-RADS 4
      lesions.
AB  - The present study aimed at evaluating and comparing the diagnostic performance of
      B-mode ultrasound (US), elastography score (ES), and strain ratio (SR) for the
      differentiation of breast lesions. This retrospective study enrolled 431 lesions
      from 417 in-hospital patients. All patients were examined with both conventional
      ultrasound and elastography. Two experienced radiologists reviewed ultrasound and
      elasticity images. The histopathologic result obtained from ultrasound-guided
      core biopsy or operation excisions were used as the reference standard.
      Pathologic examination revealed 276 malignant lesions (64%) and 155 benign
      lesions (36%). A cut-off point of 4.15 (area under the curve, 0.891) allowed
      significant differentiation of malignant and benign lesions. ROC (receiver
      operating characteristic) curves showed a higher value for combination of B-mode
      ultrasound and elastography for the diagnosis of breast lesions. Conventional
      ultrasound combined elastography showed high sensitivity, specificity, and
      accuracy for group II lesions (10mm<lesion diameter <=20mm). Elastography
      combined with conventional ultrasound show high specificity and accuracy for
      differentiation of benign and malignant breast lesions. Elastography is
      particularly important for the diagnosis of BI-RADS 4 and small breast lesions. 

PMID- 25605167
TI  - Descriptive epidemiology of common female cancers in the north East India--a
      hospital based study.
AB  - BACKGROUND: Cancers of the breast, uterine cervix and ovary are common cancers
      amongst females of North East India. Not much is known about the descriptive
      epidemiology of these cancers in our population. The present retrospective
      analysis was therefore performed. MATERIALS AND METHODS: The data set available
      at the hospital based cancer registry of a regional cancer center of North-East
      India, containing information on patients registered during the period of January
      2010 to December 2012, was applied. A total of 2,925 cases of breast, uterine
      cervix and ovarian cancer were identified. RESULTS: Of the total, 1,295 (44.3%)
      were breast cancers, 1,214 (41.5%) were uterine cervix and 416 (14.2%) ovarian
      cancer, median age (range) for breast, uterine cervix and ovary were 45 (17-85),
      48 (20-91) and 45 years (7-80), respectively. Some 43.5% of cases with uterine
      cervix patients were illiterate, 5.4% and 5.7% stage I in breast and cervix
      respectively and 96.4% of ovarian cancers in advanced stage. CONCLUSIONS:
      Improvement of female education can contribute to increase the proportion of
      early stage diagnosis of breast and uterine cervix in our population. Any
      population-based intervention for the detection of cancers of breast, uterine
      cervix and ovarian cancer should be started early in our population.

PMID- 25605169
TI  - Irinotecan as a palliative therapy for metastatic breast cancer patients after
      previous chemotherapy.
AB  - BACKGROUND: This analysis was conducted to evaluate the efficacy and safety of
      irinotecan based chemotherapy for treatment of patients with metastatic breast
      cancer (MBC) who experienced disease progression after one to three chemotherapy
      regimens, including at least one anthracycline- or taxane-based. METHODS:
      Clinical studies were identified using a predefined search strategy. Pooled
      response rates (RR) to treatment were calculated. RESULTS: As irinotecan based
      regimens, 5 clinical studies which including 217 patients with refractory MBC
      were considered eligible for inclusion, with irinotecan, cisplatin, capecitabine,
      or TS-1. Systemic analysis suggested that, in all patients, pooled RR was 48.8%
      (106/217) with irinotecan based regimens. Thrombocytopenia and leukocytopenia
      were the main side effects. No grade III or IV renal or liver toxicity was
      observed. No treatment related deaths occurred. CONCLUSION: This systemic
      analysis suggests that irinotecan based regimens are beneficial and safe for
      treating patients with MBC after other chemotherapy.

PMID- 25605170
TI  - Assessment of the effects of breast cancer training on women between the ages of
      50 and 70 in Kemalpasa, Turkey.
AB  - BACKGROUND: In both developed and developing countries; breast cancer is the
      major cancer observed in women. The aim of this study was to assess the effect of
      nursing and mammographic intervention on women with breast cancer between the
      ages of 50 and 70. MATERIALS AND METHODS: A training program, which was quasi-
      experimental and had a pretest-protest design, was applied in Kemalpas?a district
      of Izmir, between October 2008 and August 2010. The target population was women
      between the ages of 50 and 70, who were registered in the list of 3rd Family
      Medicine Unit in Izmir's Kemalpas?a metropolis. A total of 106 women who were in
      conformity with the study criteria participated in the study. Research data were
      collected through home visits that included face-to-face interviews; Ministry of
      Health education material and video films were modified and used for the
      training. Data analysis was performed through 82 women who were paired at the
      first and the second phase. RESULTS: It was observed that although the rate of
      breast self examination significantly increased after the training (p=0.022), the
      rate of clinical breast examination (p=0.122) and mammographic screening
      (p=0.523) did not. Differences in the stages of change after training were found
      to be statistically significant (p<0.001) and the group showed a progression in
      the stages of change in general (46.3%). In women mean scores of breast cancer
      awareness (p<0.000), severity (p<0.000), health motivation (p<0.000) and
      perception of the benefits of mammography (p<0.000) increased significantly and
      mean score of perception of mammography barriers decreased significantly
      (p<0.000) after the training. CONCLUSIONS: After the training on breast cancer
      and mammography it was determined that nursing interventions provided positive
      progression of stages of change of women, affected health beliefs positively and
      significantly increased BSE incidences. However, it did not have a significant
      effect on CBE and mammographic screening.

PMID- 25605171
TI  - Cervical screening using visual inspection with acetic acid (VIA) and treatment
      with cryotherapy in Fiji.
AB  - The purpose of this study was to demonstrate the feasibility of VIA screening
      with cryotherapy and to record normative values for indicators anticipated in
      similar low resource settings. Women aged 30-49 years were targeted, resulting in
      1961 women screened and treated at two primary health care (PHC) centres near
      Suva, Fiji. Recruitment was through provision of information, education and
      communication (IEC). Referrals to a gynaecology outpatient department (OPD) at a
      referral hospital occurred throughout the screening pathway. Participation was
      32% (95%CI 31-33%), higher in iTaukei (Melanesians) women (34%, 95%CI 33-36)
      compared to Fijians of Indian descent (26%, 95%CI 24-28). Regression analysis,
      adjusted for confounders, indicated significantly lower participation in those of
      Indian descent, and age groups 35-39 and 45-49 years. Of those examined by VIA,
      190 were positive with aceto-white lesions (9.9%), within the expected range of 8
      15%, with minor geographic and ethnic variation. Positive VIA results were more
      common in the peri-urban area, and in those aged 35-39 years. Of women aged 30-49
      years, 59 received cryotherapy (none of whom had significant complications), 91
      were referred to OPD, two cervical carcinomas were identified and eight cervical
      intra-epithelial neoplasms (CIN) II-III were diagnosed. These results provide
      normative findings from a community-based VIA screening program for other similar
      low resource settings. 

PMID- 25605172
TI  - Incidence and predictors of inadequate bowel preparation before elective
      colonoscopy in Thai patients.
AB  - BACKGROUND: The incidence of inadequate bowel preparation before elective
      colonoscopy in this region has never been studied. MATERIALS AND METHODS: The
      authors prospectively described the incidence and factors related to inadequate
      bowel preparation in Thammasat university hospital. Bowel preparation quality was
      accessed by using Aronchick scale. Factors associated with inadequate bowel
      preparation were also recorded. RESULTS: Two hundred patients undergoing elective
      outpatient colonoscopy were enrolled. Inadequate and fair bowel preparation was
      documented in 9 and 43%, respectively. Factors associated with inadequate bowel
      preparation were incomplete cleansing agent ingestion (odds ratio 7.7; 95%CI 1.62
      36.64) and patient's unrecognization of vegetable avoidance (odds ratio 3.26;
      95%CI 1.14-9.28). CONCLUSIONS: Compared with previous reported, inadequate bowel
      preparation was seen less in our study, however, more patients with fair bowel
      preparation was documented. Further study aiming at investigating the type and
      amount of fiber contained in diet before elective colonoscopy should be
      commenced.

PMID- 25605173
TI  - Anti-VEGF Therapy with Bevacizumab--limited cardiovascular toxicity.
AB  - PURPOSE: This analysis was conducted to evaluate cardiovascular toxicity of
      commonly used anti-VEGF therapeutic agent, bevacizumab, in treating patients with
      cancer. METHODS: Clinical studies evaluating the efficacy and safety of
      bevacizumab-based regimens on response and safety for patients with cancer were
      identified using a predefined search strategy, allowing cardiovascular toxicity
      and other side effects of treatment to be estimated. RESULTS: In bevacizumab
      based regimens, 4 clinical studies including 282 patients with advanced cancer
      (including gliomas, cervical, breast and ovarian cancer) were considered eligible
      for inclusion. These bevacizumab-based regimens included docetaxel, irinitecan
      and carboplatin. Systematic analysis suggested that, of 282 patients treated by
      bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5%
      (7/282), while only 3 patients reported cardiovascular events (1.1%). No
      treatment related death occurred in bevacizumab based treatment. CONCLUSION: This
      systemic analysis suggests that bevacizumab based regimens are associated with
      reasonable and accepted cardiovascular toxicity when treating patients with
      gliomas, cervical, breast and ovarian cancer.

PMID- 25605174
TI  - Legumain protein as a potential predictive biomarker for Asian patients with
      breast carcinoma.
AB  - BACKGROUND: Treatment for breast cancer is mainly performed by surgical resection
      of primary tumors and chemotherapy. However, after tumor invasion and metastases,
      breast cancer is hard to control. Clarification of the pathogenic mechanisms
      would be helpful to the prognosis or therapy for the breast cancer. The aim of
      this study is to investigate the clinical and prognostic implications of legumain
      protein Materials and Methods: In this study, we examined mastectomy specimens
      from 114 breast cancer and matching, 26 adjacent non-cancerous tissues using
      immunohistochemistry. RESULTS: The results indicated that positive expression of
      legumain protein in breast cancer was 51.8 % (59/114) and the positive expression
      of legumain protein in adjacent non-cancerous tissue was 11.5% (3/26). It
      appeared to be related with lymph node metastasis of breast cancer (p=0.02) and
      correlation analysis indicated that legumain expression was correlated positively
      with the estrogen receptor (ER) and mutant-type p53 expression (both p<0.05).
      Positive legumain expression was significantly associated with shorter overall
      survival time in breast cancer patients (log-rank p<0.01). Multivariate survival
      analysis suggested that the positive legumain expression was an independent
      predictor of poorer overall survival in patients with breast cancer (HR=0.24;
      95%CI 0.11-0.65, p=0.03). CONCLUSIONS: Legumain might be a new potential
      biomarker for breast cancer, which may reflect the prognosis and overall
      survival.

PMID- 25605175
TI  - Epidemiology of pancreatic cancer in vojvodina province in Serbia.
AB  - PURPOSE: Analysis of descriptive epidemiological characteristics of pancreatic
      cancer in Vojvodina, Serbia. MATERIALS AND METHODS: The study covers population
      of Vojvodina in the period from 2000 to 2009. The method used for data processing
      was the descriptive. The data, referring to a specified period of time, were
      analyzed from chronological and demographic aspects and according to histological
      diagnosis. RESULTS: In the period from 2000 to 2009, there were 2,108 registered
      cases of pancreatic cancer of which 1,886 had a fatal outcome. Standardized
      incidence rates varied between 5.7 and 9.1 per 100,000 population in males and
      between 4.2 and 5.3 in females. Linear incidence trends in males in the specified
      period of time, based on crude (r=0.7883, p<0.05) and standardized (r=0,6373,
      p<0,05) incidence rates, demonstrated increase. Annual percent increase in the
      crude incidence rate was 4.5% in males, and 2.8% in females. Age-standardized
      mortality rates varied between 5.2 and 7.5 per 100,000 population in males and
      3.6 and 4.7 in females. Linear mortality trends in males in the specified period
      of time, based on crude (r=0.8795, p<0.05) and standardized (r=0.7669, p<0.05)
      mortality rates, also demonstrated annual percent increase. CONCLUSIONS: Data
      analysis shows unfavorable onco-epidemiological situation related to pancreatic
      cancer in Vojvodina, in aspects of both incidence and mortality. Absence of
      primary and secondary prevention does not allow medical institutions to
      successfully fight against this disease.

PMID- 25605176
TI  - Effectiveness of tobacco education for pharmacy students in Indonesia.
AB  - BACKGROUND: Smoking remains the major preventable cause of death worldwide,
      especially cancer-related death. Evidence clearly indicates that tobacco-related
      morbidity and mortality is reduced by smoking cessation. Pharmacists are well
      positioned to provide tobacco cessation services an involvement of pharmacists in
      smoking cessation is encouraged by several organizations. While Indonesia's
      prevalence of smoking is in the first rank in Asian countries, none of the
      pharmacy schools in Indonesia are currently offering tobacco-related courses in
      their existing curricula at present. Our study aimed to develop and to evaluate
      the effectiveness of tobacco education (TE) for pharmacy students in Indonesia.
      MATERIALS AND METHODS: A 6-hour TE was developed and evaluated using pre
      test/post-test with control group design. A total of 137 fifth-year pharmacy
      students at Gadjah Mada University (GMU), Yogyakarta, were chosen as an
      intervention group while a total of 105 fifth-year students of Islamic University
      of Indonesia, (UII) served as the control group. Knowledge, perceived-role, self
      efficacy, and ability to perform counseling using the 5A's framework were
      evaluated. RESULTS: A significant improvement (P < 0.001) in knowledge, perceived
      role, and self-efficacy was found in the intervention group but not in the
      control group. In addition, we revealed that 89.7% of the intervention group were
      able to perform counseling using 5A's. CONCLUSIONS: The developed TE
      significantly improved student knowledge, perceived-rolse, self-efficacy, and
      created an ability to perform cessation counseling. Integration of TE education
      in curricula of Indonesian pharmacy schools nation-wide should be encouraged.

PMID- 25605177
TI  - Ovarian cancer in Iranian women, a trend analysis of mortality and incidence.
AB  - BACKGROUND: Ovarian cancer is an important cause of mortality in women. The aim
      of this study was to evaluate the incidence and mortality rates and trends in the
      Iranian population and make predictions. MATERIALS AND METHODS: National
      incidence from Iranian annual of National Cancer Registration report from 2003 to
      2009 and National Death Statistics reported by the Ministry of Health and Medical
      Education from 1999 to 2004 were included in this study. A time series model
      (autoregressive) was used to predict the mortality for the years 2007, 2008, 2012
      and 2013, with results expressed as annual mortality rates per 100,000. RESULTS:
      The general mortality rate of ovarian cancer slightly increased during the years
      under study from 0.01 to 0.75 and reaching plateau according to the prediction
      model. Mortality was higher for older age. The incidence also increased during
      the period of the study. CONCLUSIONS: Our study indicated remarkable increasing
      trends in ovarian cancer mortality and incidence. Therefore, attention to high
      risk groups and setting awareness programs for women are needed to reduce the
      associated burden in the future.

PMID- 25605178
TI  - Comparison of clinical characteristics between benign borderline and malignant
      phyllodes tumors of the breast.
AB  - BACKGROUND: Phyllodes tumors of the breast are rare fibroepithelial lesions, so
      relatively little is known about this disease entity. The present study was
      designed to identify differences in clinical features between benign borderline
      and malignant phyllodes tumors. MATERIALS AND METHODS: Data from 246 women with
      phyllodes tumors of the breast treated in Cancer Hospital Chinese Academy of
      Medical Sciences between 2002 and 2012 were collected and analyzed, including age
      at presentation, age at treatment, course, size of primary tumor, location,
      histological type, type of surgery and treatment, local recurrence, distant
      metastasis, fibroadenoma history, disease-free survival and number of mitosis per
      10hpf. There are 125 (55%) benign, 55 (24%) borderline and 47 (21%) malignant
      tumors. RESULTS: In univariate analysis, average age at presentation, average age
      at treatment, size of primary tumor, ulceration or not, type of primary surgery,
      distant metastasis and number of mitosis per 10 hpf turned out to be
      statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003,
      <0.000, 0.001 and <0.000, respectively), while recurrence and disease-free
      survival (DFS) demonstrated trends for statistical significance (P =0.055 and
      0.060, respectively). Multivariate analysis revealed distant metastasis and
      excision were significantly different in benign, borderline and malignant
      phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the
      same time, size of primary tumor with p=0.052 tended to be different between
      groups (OR=1.127). However, age at treatment, ulceration and DFS showed no
      statistically significant variation (p=0.400, 0.286 and 0.413, respectively).
      CONCLUSIONS: Benign borderline and malignant phyllode tumors have different
      distant metastasis risk, different primary tumor size and different surgical
      procedures, and malignant PTs are more likely to be bigger and to metastasize.

PMID- 25605179
TI  - Identification and functional analysis of differentially expressed genes related
      to metastatic osteosarcoma.
AB  - BACKGROUND: To explore the molecular mechanisms of metastatic osteosarcoma (OS)
      by using the microarray expression profiles of metastatic and non-metastatic OS
      samples. MATERIALS AND METHODS: The gene expression profile GSE37552 was
      downloaded from Gene Expression Omnibus database, including 2 human metastatic OS
      cell line models and 2 two non-metastatic OS cell line models. The differentially
      expressed genes (DEGs) were identified by Multtest package in R language. In
      addition, functional enrichment analysis of the DEGs was performed by WebGestalt,
      and the protein-protein interaction (PPI) networks were constructed by
      Hitpredict, then the signal pathways of the genes involved in the networks were
      performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation
      server (KAAS). RESULTS: A total of 237 genes were classified as DEGs in
      metastatic OS. The most significant up- and down-regulated genes were A2M (alpha
      2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the
      response to hormone stimulus, and the PPI network of A2M contained IL1B
      (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF
      (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and
      focal adhesion were significantly enriched. CONCLUSIONS: A2M and its interactive
      proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to
      monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK
      signaling pathway and focal adhesion may play important roles in metastatic OS.

PMID- 25605180
TI  - p16INK4A expression in squamous cell carcinomas of the vagina and the vulva in
      Tunisian women.
AB  - BACKGROUND: The role of p16INK4A expression in uterine cervix cancer is well
      established. In the remaining female lower genital tract cancers, the importance
      of p16INK4A up-regulation is less clear. In our study, we analyzed the role of
      p16INK4A expression and HPV infection in carcinomas of the vulva and the vagina
      in Tunisian women. MATERIALS AND METHODS: We conducted a retrospective study of
      30 carcinomas including 15 vulvar squamous cell carcinomas (SCCs) and 15 vaginal
      SCCs. Immunohistochemistry was used to determine p16INK4A expression. HPV
      detection and typing was by in situ hybridization. RESULTS: p16INK4A expression
      was detected in 86.7% of vaginal SCCs with a strong and diffuse immunostaining in
      60% of cases, and also in 73.3% of vulvar SCCs with focal immunoreactivity in
      53.3% The association between p16INK4A expression and HPV infection was
      significant in vaginal SCCs (p=0.001) but not vulvar SCCs (p>0.05). CONCLUSIONS:
      p16INK4A expression could be used as a useful marker for HPV positivity in
      vaginal SCCs similar to that described in uterine cervix cancers. However, our
      data support the presence of 2 different mechanisms for p16INK4A expression in
      HPV-related and HPV-unrelated vulvar carcinomas.

PMID- 25605181
TI  - Comparison of detection sensitivity for human papillomavirus between self
      collected vaginal swabs and physician-collected cervical swabs by electrochemical
      DNA chip.
AB  - BACKGROUND: Human papillomavirus (HPV) DNA testing is an effective method to
      screen for precancerous changes in the cervix. Samples from self-collection
      rather than Pap smear can potentially be used to test for HPV as they are more
      acceptable and preferred for use in certain settings. The objective of this study
      was to compare HPV DNA testing from self-collected vaginal swabs and physician
      collected cervical swabs. MATERIALS AND METHODS: A total of 101 self-collected
      vaginal and physician-collected cervical swabs of known cytology from Thai women
      were tested by electrochemical DNA chip assay. The specimens were divided into 4
      groups: 29 with normal cytology, 14 with atypical squamous cells of undetermined
      significance (ASCUS), 48 with low- grade squamous intraepithelial lesion (LSIL),
      and 10 with high-grade squamous intraepithelial lesion (HSIL). RESULTS: Positive
      detection rates of HPV from self-collected swabs were similar to those from
      physician-collected swabs. Among specimens with abnormal cytology, HPV was found
      in 50% of self-collected swabs and 47.2% of physician-collected swabs. In
      specimens with normal cytology, 17.2% of self-collected swabs and 24.1% of
      physician-collected swabs were positive for HPV. Concordance was relatively high
      between results from self- collected and physician-collected samples. The most
      common HPV genotype detected was HPV 51. CONCLUSIONS: HPV DNA testing using self
      collected swabs is a feasible alternative to encourage and increase screening for
      cervical cancer in a population who might otherwise avoid this important
      preventive examination due to embarrassment, discomfort, and anxiety.

PMID- 25605183
TI  - A novel all-trans retinoid acid derivative induces apoptosis in MDA-MB-231 breast
      cancer cells.
AB  - AIMS: To explore the effect and probable mechanism of a synthetic retinoid 4
      amino-2-tri-fluoromethyl- phenyl ester (ATPR) on apoptosis of MDA-MB-231 breast
      cancer cells. MATERIALS AND METHODS: MTT assays were performed to measure the
      proliferation of MDA-MB-231 cells treated with different concentrations of all-
      trans retinoic acid (ATRA) and ATPR. Morphologic changes were observed by
      microscopy. The apoptosis rates and cell cycling of MDA-MB-231 cells treated with
      ATRA or ATPR were assessed using flow cytometry analysis. Expression of retinoic
      acid receptor and phosphorylation of ERK, JNK, p38 proteins were detected by
      Western blotting. RESULTS: Treatment of the cells with the addition of 15 MUmol/L
      ATPR for 48 h clearly demonstrated reduced cell numbers and deformed cells,
      whereas no changes in the number and morphology were observed after treatment
      with ATRA. The apoptosis rate was 33.2% after breast cancer MDA-MB-231 cells were
      treated by ATPR (15 MUmol/L) whereas ATRA (15 MUmol/L) had no apoptotic effect.
      ATPR inhibited the phosphorylation of ERK, JNK, and p38 while ATRA had no
      significant effect. ATPR inhibited the expression of BiP and increased the
      expression of Chop at the protein level compared with control groups, ATRA and
      ATPR both decreased the protein expression of RXR alpha, ATPR reduced the protein
      expression of RARbeta and RXRbeta while ATRA did not decrease RARbeta or RXRbeta.
      CONCLUSIONS: ATPR could induce apoptosis of breast cancer MDA-MB-231 cells,
      possible mechanisms being binding to RARbeta/RXRbeta heterodimers, then
      activation of ER stress involving the MAPK pathway.

PMID- 25605182
TI  - Prognostic significance of Nestin expression in pT1 high- grade bladder
      urothelial carcinoma patients treated with intravesical BCG.
AB  - BACKGROUND: Possible roles of nestin expression in terms of predicting
      intravesical BCG therapy response in T1 high grade bladder cancer patients were
      investigated. MATERIALS AND METHODS: T1 high grade bladder cancer patients who
      were treated with intravesical BCG between 1990-2009 were included.
      Immunohistochemical staining for nestin expression was performed. Nestin(+) and
      nestin(-) patients were compared in terms of recurrence and progression rates.
      RESULTS: Sixty-three patients were included and median follow-up time was twenty
      five months. After staining; 33 patients (52.4%) were classified as nestin (+)
      and 30 (47.6%) as (-). Nestin (+) patients were more likely to recur compared to
      nestin (-) patients (60.6% vs. 30%, p<0.05). Progression rates were also higher
      in nestin (+) patients, although this result did not reach statistical
      significance (15.2 % vs. 10 %, p=0.710). CONCLUSIONS: Nestin expression, which
      seems effective in predicting recurrence, appears to have a potential role in the
      urothelial carcinoma tumorigenesis. Patients with high grade bladder cancer and
      positive nestin expression need close follow-up and might be informed about more
      tendency to recur. Further comprehensive studies including larger patient cohorts
      may clarify the role of nestin in bladder cancer.

PMID- 25605184
TI  - Inhibitory effects of phenolic alkaloids of Menispermum dauricum on gastric
      cancer in vivo.
AB  - The present study was conducted to investigate effects and mechanisms of action
      of phenolic alkaloids of Menispermum dauricum (PAMD) on gastric cancer in vivo.
      In vitro, cell apoptosis of human gastric cancer cell line SGC-7901 was observed
      using fluorescence staining. In vivo, a mice model was constructed to observe
      tumor growth with different doses. Cell apoptosis was examined using flow
      cytometry and K-RAS protein expression using Western blotting. The mRNA
      expression of P53, BCL-2, BAX, CASPASE-3, K-RAS was examined by real-time PCR.
      PAMD significantly suppressed tumor growth in the xenograft model of gastric
      cancer in a dose- dependent manner (p<0.01). Functionally, PAMD promoted cell
      apoptosis of the SGC-7901 cells and significantly increased the rate of cell
      apoptosis of gastric tumor cells (p<0.05). Mechanically, PAMD inhibited the
      expression of oncogenic K-RAS both at the mRNA and protein levels. In addition,
      PAMD affected the mRNA expression of the cell apoptosis-related genes (P53, BCL
      2, BAX, CASPASE-3). PAMD could suppress gastric tumor growth in vivo, possibly
      through inhibiting oncogenic K-RAS, and induce cell apoptosis possibly by
      targeting the cell apoptosis-related genes of P53, BCL-2, BAX, CASPASE-3. 

PMID- 25605185
TI  - Elevated preoperative platelet to lymphocyte ratio associated with decreased
      survival of women with ovarian clear cell carcinoma.
AB  - This study was conducted to establish whether the preoperative platelet to
      lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell
      carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival
      (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard
      analysis was used to determine the independent effect of PLR. Thirty-six patients
      were reviewed. Elevated PLRs were more commonly noted in patients with an
      advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR
      carried a higher rate of disease progression during primary therapy than that
      those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with
      elevated PLR was notably worse than that for patients with normal PLR (10 vs 34
      months). Despite the impact of elevated PLR on PFS, it was found to be marginally
      significant when controlling for commonly applied prognostic markers. It,
      however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion,
      an elevated PLR appears to be directly associated with adverse survival rather
      than being a surrogate for other indicators of a poor prognosis. PLR may be a
      useful biomarker for predicting survival of women with OCCC and merits further
      large-scale studies. 

PMID- 25605186
TI  - Survival outcomes of recurrent epithelial ovarian cancer: experience from a
      Thailand northern tertiary care center.
AB  - To assess survival outcomes in a retrospective study, recurrent epithelial
      ovarian cancer patients were divided into three groups according to the platinum
      free interval as follows: platinum refractory that included the patients with
      tumor progression during treatment; platinum resistant and platinum sensitive
      that included the patients with tumor progression less than or more than six
      months, respectively. Clinical data for tumor progression in epithelial ovarian
      cancer patients treated at Chiang Mai University Hospital between January, 2006
      and December, 2010 were reviewed. Thirty-nine patients were in the platinum
      refractory group while 27 were in the platinum resistant group and 75 in the
      platinum sensitive group. The mean age, the parity, the administration of
      neoadjuvant chemotherapy and the serous type did not significantly different
      across groups while the mean total number of chemotherapy regimens, the early
      stage patients, the patients with complete surgery and the surviving patients
      were significant more frequent in the platinum sensitive group. Regarding
      subsequent treatment after tumor recurrence, 87.2% underwent chemotherapy. With
      the median follow up time at 29 months, the median overall survival rates were 20
      months, 14 months and 42 months in platinum refractory, platinum resistant and
      platinum sensitive groups, respectively (p<0.001). In addition, when the platinum
      sensitive patients developed the next episode of tumor progression, the median
      progression free interval time was only three to four months. In conclusion, the
      outcomes for platinum refractory the and platinum resistant groups was poorer
      than the platinum sensitive group. However, subsequent progression in the
      platinum sensitive group was also associated with a poor outcome. 

PMID- 25605187
TI  - Pattern of shisha and cigarette smoking in the general population in Malaysia.
AB  - BACKGROUND: Smoking is a primary risk factor for cancer development. While most
      research has focused on smoking cigarettes, the increasing popularity of shisha
      or water pipe smoking has received less attention. This study measured the
      prevalence and risk factors for shisha and cigarette smoking and related
      knowledge. MATERIALS AND METHODS: This cross-sectional analytical study was
      conducted in Shah Alam, Malaysia. Participants aged >= 18 years were selected
      from restaurants. Data regarding demographic variables, smoking patterns, and
      knowledge about shisha smoking were collected in local languages. Logistic
      regression was performed to assess risk factors. RESULTS: Of 239 participants,
      61.9 % were male and 99.2% revealed their smoking status. Some 57.4% were
      smokers: 50.7% only cigarettes, 5.9% only shisha and 42% both. Mean age of
      starting cigarette smoking was 17.5 +/- 2.4 years and for shisha smoking 18.7 +/-
      2.0 years. In a univariate model, male gender, age 33-52 years and monthly income
      > MYR 4,000 increased the risk and unemployment and being a student decreased the
      risk. In a multivariate model, male gender increased the risk of smoking, while
      being a student decreased the risk, adjusting for age and income. The perception
      of shisha being less harmful than cigarettes was present in 14.6% and 7.5% had
      the opinion that shisha is not harmful at all, while 21.7% said that it is less
      addictive than cigarettes, 39.7% said that shisha did not contain tar and
      nicotine, 34.3% said that it did not contain carbon monoxide and 24.3% thought
      that shisha did not cause health problems. CONCLUSIONS: Prevalence of shisha and
      cigarette smoking is high in the general population in Malaysia and knowledge
      about shisha smoking is relatively low. The findings of our study might have
      implications for understanding similarities and differences in incidence of
      shisha and cigarette smoking in other cultural/geographic regions.

PMID- 25605188
TI  - Identifying differentially expressed genes and screening small molecule drugs for
      lapatinib-resistance of breast cancer by a bioinformatics strategy.
AB  - BACKGROUND: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the
      epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated
      to have significant efficacy in treating HER2-positive breast cancer. However,
      acquired drug resistance has become a very serious clinical problem that hampers
      the use of this agent. In this study, we aimed to screen small molecule drugs
      that might reverse lapatinib-resistance of breast cancer by exploring
      differentially expressed genes (DEGs) via a bioinformatics method. MATERIALS AND
      METHODS: We downloaded the gene expression profile of BT474-J4 (acquired
      lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene
      Expression Omnibus (GEO) database and selected differentially expressed genes
      (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses
      were performed with the DAVID database. Finally, a connectivity map was utilized
      for predicting potential chemicals that reverse lapatinib-resistance. RESULTS: A
      total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways,
      including cell cycling, regulation of actin cytoskeleton and focal adhesion
      associate examples. In addition, several small molecules were screened as the
      potential therapeutic agents capable of overcoming lapatinib-resistance.
      CONCLUSIONS: The results of our analysis provided a novel strategy for
      investigating the mechanism of lapatinib-resistance and identifying potential
      small molecule drugs for breast cancer treatment.

PMID- 25605189
TI  - Intravenous flurbiprofen axetil enhances analgesic effect of opioids in patients
      with refractory cancer pain by increasing plasma beta-endorphin.
AB  - BACKGROUND: The study aimed to investigate the analgesic effect of a combination
      of intravenous flurbiprofen axetil and opioids, and evaluate the relationship
      between refractory pain relief and plasma beta-endorphin levels in cancer
      patients. MATERIALS AND METHODS: A total of 120 cancer patients was randomly
      divided into two groups, 60 patients took orally morphine sulfate sustained
      release tablets in group A, and another 60 patients receiving the combination
      treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7
      days, pain relief, quality of life improvement and side effects were evaluated.
      Furthermore, plasma beta-endorphin levels were measured by radioimmunoassay.
      RESULTS: With the combination treatment of intravenous intravenous flurbiprofen
      axetil and opioids, the total effective rate of pain relief rose to 91.4%, as
      compared to 82.1% when morphine sulfate sustained-release tablet was used alone.
      Compared with that of group A, the analgesic effect increased in group B
      (p=0.031). Moreover, satisfactory pain relief was associated with a significant
      increase in plasma beta-endorphin levels. After the treatment, plasma beta
      endorphin level in group B was 62.4+/-13.5 pg/ml, which was higher than that in
      group A (45.8+/-11.2 pg/ml) (p<0.05). CONCLUSIONS: Our results suggest the
      combination of intravenous flurbiprofen axetil and opioids can enhance the
      analgesic effect of opioid drugs by increasing plasma beta-endorphin levels,
      which would offer a selected and reliable strategy for refractory cancer pain
      treatment.

PMID- 25605190
TI  - Public awareness and knowledge of oral cancer in Yemen.
AB  - BACKGROUND: Oral cancer is in increasing in incidence in Yemen and indeed
      worldwide. Knowledge regarding risk factors and early signs in the general
      population can help in prevention and early detection of the disease. PURPOSE:
      The aim of this study was to assess the level of awareness and knowledge of oral
      cancer in the general population in Yemen. MATERIALS AND METHODS: A cross
      sectional survey using a self-administered questionnaire was conducted on Yemeni
      adults aged >=15 years old. A total of 543 persons participated, the collected
      data being analyzed using SPSS software. The significance level was set at
      p<0.05. RESULTS: Two thirds (71.5%) of the participants had heard about oral
      cancer. Smoking and smokeless tobacco usage were identified as the major risk
      factors by 71.5% and 73.7% of the participants, respectively. Only 24.1% and
      21.4%, respectively, were able to correctly identify red and white lesions as
      early signs of oral cancer. Knowledge of oral cancer was significantly associated
      with age (p<0.01), gender (p<0.05) and education level (p<0.001). CONCLUSIONS:
      The findings suggest that the knowledge regarding oral cancer in this population
      is low. Therefore, educational programs are highly needed to improve such
      knowledge.

PMID- 25605191
TI  - Educational levels and delays in start of treatment for head and neck cancers in
      North-East India.
AB  - BACKGROUND: There are various patient and professional factors responsible for
      the delay in start of treatment (SOT) for head and neck cancers (HNC). MATERIALS
      AND METHODS: This retrospective study was conducted on data for HNC patients
      registered at the hospital cancer registry in North-East India. All cases
      diagnosed during the period of January 2010 to December 2012 were considered for
      the present analysis. Educational levels of all patients were clustered into 3
      groups; illiterates (unable to read or write), qualified (school or high school
      level education), and highly qualified (college and above). RESULTS: In the
      present analysis 1066 (34.6%) patients were illiterates, 1,869 (60.6%) patients
      were literates and 145 (4.7%) of all patients with HNC were highly qualified. The
      stage at diagnosis were stage I, seen in 62 (34.6%), stage II in 393 (12.8%),
      stage III in 1,371 (44.5%) and stage IV in 1,254 (40.7%) . The median time (MT)
      to the SOT from date of attending cancer hospital (DOACH) was, in illiterate
      group MT was 18 days, whereas in the qualified group of patients it was 15 days
      and in the highly qualified group was 10 days. Analysis of variance showed there
      was a significant difference on the mean time for the delay in SOT from DOACH for
      different educational levels (F=9.923, p=0.000). CONCLUSIONS: Educational level
      is a patient related factor in the delays for the SOT in HNCs in our population.

PMID- 25605192
TI  - Quality of life in gestational trophoblastic neoplasia patients after treatment
      in Thailand.
AB  - BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a malignant disease
      which occurs in women of reproductive age. Treatment of GTN has an excellent
      outcome and further pregnancies can be expected. However, data concerning quality
      of life in these cancer survivor patients are limited. This study aimed to assess
      quality of life in women who were diagnosed with GTN and remission after
      treatment, and to determine factors that may affect quality of life status.
      MATERIALS AND METHODS: This cross sectional study was conducted from July 2013 to
      May 2014 in the Gestational Trophoblastic Disease Clinic, King Chulalongkorn
      Memorial Hospital, Bangkok, Thailand. Patients who were diagnosed GTN and
      complete remission were recruited. Data collection was accomplished by interview
      with two sets of questionnaires, one general covering demographic data and the
      other focusing on quality of life, the fourth version of Functional Assessment of
      Cancer Therapy (FACT-G). Descriptive statistics were used to determine general
      data and quality of life scores. Students t-test and one way ANOVA were used to
      compare between categorical and continuous data. RESULTS: Forty four patients
      were enrolled in this study. The overall mean quality of life score (FACT-G) was
      98.2. The overall FACT-G score was not significantly correlated with age,
      education level, stage of disease, treatment modalities, and time interval from
      remission to enrollment. However, patients who needed further fertility showed
      significant lower FACT-G scores in the emotional well-being domain (p=0.02).
      CONCLUSIONS: Overall quality of life scores in post-treatment gestational
      trophoblastic neoplasia patients are in the mild impairment range. Patients who
      desire fertility suffer lower quality of life in the emotional well-being domain.

PMID- 25605193
TI  - B3GNT2, a polylactosamine synthase, regulates glycosylation of EGFR in H7721
      human hepatocellular carcinoma cells.
AB  - The epidermal growth factor receptor (EGFR) is an important surface receptor with
      N-glycans in its extracellular domain, whose glycosylation is essential for its
      function, especially in tumor cells. Here, we demonstrated that polylactosamine
      is markedly increased in H7721 hepatocellular carcinoma cells after treatment
      with EGF, while it apparently declined after exposure to all-trans retinoic acid
      (ATRA). In the study of the enzymatic mechanism of this phenomenon, we explored
      changes in the expression of poly-N-acetyllactosamine (PLN) branching
      glycosyltransferases using RT-PCR. Among the four glycosyltransferases with
      altered expression, GnT-V was most elevated by EGF, while GnT-V and B3GNT2 were
      most declined by ATRA. Next, we conducted co-immunoprecipitation experiments to
      test whether B3GNT2 and EGFR associate with each other. We observed that EGFR is
      a B3GNT2-targeting protein in H7721 cells. Taken together, these findings
      indicated that the altered expression of B3GNT2 will remodel the PLN stucture of
      EGFR in H7721 cells, which may modify downstream signal transduction. 

PMID- 25605194
TI  - Effect of intraoperative glucose fluctuation and postoperative IL-6, TNF-alpha,
      CRP levels on the short-term prognosis of patients with intracranial
      supratentorial neoplasms.
AB  - OBJECTIVE: To investigate the effect of intraoperative glucose fluctuation and
      postoperative interlukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C
      reactive protein (CRP) levels on the short-term prognosis of patients with
      intracranial supratentorial neoplasms. MATERIALS AND METHODS: Eighty-six patients
      undergoing intracranial excision were selected in The Second Hospital of Jilin
      University. According to the condition of glucose fluctuation, the patients were
      divided into group A (glucose fluctuation <2.2 mmol/L, n=57) and group B (glucose
      fluctuation >=2.2 mmol/L, n=29). Glucose was assessed by drawing 2 mL blood from
      internal jugular vein in two groups in the following time points, namely fasting
      blood glucose 1 d before operation (T0), 5 min after anesthesia induction (T1),
      intraoperative peak glucose (T2), intraoperative lowest glucose (T3), 5 min after
      closing the skull (T4), immediately after returning to intensive care unit (ICU)
      (T5) and 2 h after returning to ICU (T6). 1 d before operation and 1, 3 and 6 d
      after operation, serum IL-6 and TNF-alpha levels were detected with enzyme-linked
      immunosorbent assay (ELISA), and CRP level with immunoturbidimetry. Additionally,
      postoperative adverse reactions were monitored. RESULTS: There was no statistical
      significance between two groups regarding the operation time, anesthesia time,
      amount of intraoperative bleeding and blood transfusion (P>0.05). The glucose
      levels in both groups at T1~T6 went up conspicuously compared with that at T0
      (P<0.01), and those in group B at T2, T4, T5 and T6 were significantly higher
      than in group A (P<0.01). Serum IL-6, TNF-alpha and CRP levels in both groups 1,
      3 and 6 d after operation increased markedly compared with 1 d before operation
      (P<0.01), but the increased range in group A was notably lower than in group B
      (P<0.05 or P<0.01). Postoperative incidences of hypoglycemia, hyperglycemia and
      myocardial ischemia in group A were significantly lower than in group B (P<0.05),
      and respiratory support time obviously shorter than in group B (P<0.01).
      CONCLUSIONS: The glucose fluctuation of patients undergoing intracranial excision
      is related to postoperative IL-6, TNF-alpha and CRP levels and those with small
      range of glucose fluctuation have better prognosis.

PMID- 25605195
TI  - Neutrophil to lymphocyte ratio--not an independent prognostic factor in patients
      with the myelodysplastic syndrome.
AB  - PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) was evaluated as a potential
      prognostic factor in patients with myelodysplastic syndrome (MDS). MATERIALS AND
      METHODS: Between December 2009 and April 2014, 14 female (35%) and 26 male (65%)
      MDS patients who were followed up in our hematology clinic were included in the
      study for NLR during diagnosis. Division was into two groups according to the
      NLR, and the correlation with mortality was evaluated. The prognostic
      significance of NLR regarding treatment outcome was also evaluated with
      adjustment for known confounding risk factors. RESULTS: The mortality rate of the
      patient group was 55%, and median survival was 18 months. There was no
      significant correlation between mortality and NLR at a median value of 1.8
      (p=0.75). Thrombocytopenia was observed to increase mortality (p=0.027), and
      there was a significant correlation between mortality and pancytopenia (p=0.017).
      CONCLUSIONS: This first study of NLR and mortality did not show any significant
      correlation . In centres with limited access to genetic evaluation for the
      presence of pancytopenia and/or thrombocytopenia at the time of diagnosis, a
      platelet level less than 50?109/l may be poor prognostic markers in MDS patients.

PMID- 25605196
TI  - Helicobacter pylori infection impacts on functional dyspepsia in Thailand.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is a well known major cause of
      gastric cancer and even when asymptomatic infected patients are at elevated risk.
      Functional dyspepsia (FD) is also one of the most common gastrointestinal
      diseases, which greatly impacts the quality of life. H. pylori infection and
      psychosocial stress are frequently associated with FD but limited studies have
      confirmed the relationships, especially in Southeast Asian countries. Here we
      aimed to investigate the prevalence and impact of H. pylori infection, anxiety
      and depression on Thai FD patients. MATERIALS AND METHODS: This cross-sectional
      study was conducted in a tertiary care center in Thailand, during February 2013
      January 2014. All FD patients were diagnosed and categorized by Rome III criteria
      into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS)
      groups. The Hospital Anxiety and Depression Scale was used to evaluate
      psychological status. The presence of H. pylori was defined as positive with H.
      pylori culture, positive rapid urease test or positive histology. RESULTS: Three
      hundred FD patients were included, 174 (58%) female. Overall mean age was
      54.8+15.1 years. There were 192 (64%) patients with PDS and 108 (36%) with EPS.
      H. pylori infection was demonstrated in 70 (23.3%) patients. Anxiety and
      depression were documented in 69 (23%) and 22 (7.3%), respectively. H. pylori
      infection, anxiety and depression were significantly higher in PDS than EPS
      patients (27.1% vs 16.7%; p=0.04; OR=1.86; 95%CI=1.01-3.53 and 29.7% vs 11.1%;
      p=0.0002; OR=3.4; 95%CI=1.7-7.1 and 10.4% vs 1.9%; p=0.006; OR=6.2; 95%CI=1.4
      38.9, respectively). CONCLUSIONS: H. pylori infection, anxiety and depression
      were commonly found in Thai FD patients and more prevalent in PDS than EPS. H.
      pylori eradication might be the key to success for the treatment of Thai FD
      patients and prevent the development of gastric cancer.

PMID- 25605197
TI  - Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas
      depends on IDH1 mutation.
AB  - Several molecular markers have been proposed as predictors of outcome in patients
      with glioblastomas. We investigated the prognostic significance of O6
      methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation
      status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma
      patients. A cohort of 78 patients with histologically confirmed glioblastomas
      treated with radiation therapy and chemotherapy were reviewed retrospectively. We
      evaluated the prognostic value of MGMT promoter methylation and TP53 mutation
      status with regard to progression-free survival (PFS) and overall survival (OS).
      It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53
      mutation, age, Karnofsky performance status (KFS), and extension of resection
      were independent prognostic factors. In patients with an IDH1 mutation, those
      with an MGMT methylation were associated with longer PFS (p=0.016) and OS
      (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and
      OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank).
      The MGMT promoter methylation and TP53 mutation were associated with a favorable
      outcome of patients with and without mutant IDH1, respectively. The results
      indicate that glioblastomas with MGMT methylation or TP53 mutations have improved
      survival that may be influenced by IDH1 mutation status. 

PMID- 25605198
TI  - Role of PET/CT in treatment planning for head and neck cancer patients undergoing
      definitive radiotherapy.
AB  - BACKGROUND: In this study, we aimed to investigate the benefits of 18F
      deoxyglucose positron emission tomography/computed tomography (FGD-PET/CT)
      imaging for staging and radiotherapy planning in patients with head and neck
      cancer undergoing definitive radiotherapy. MATERIALS AND METHODS: Thirty-seven
      head and neck cancer patients who had undergone definitive radiotherapy and
      PET/CT at the Uludag University Medical Faculty Department of Radiation Oncology
      were investigated in order to determine the role of PET/CT in staging and
      radiotherapy planning. RESULTS: The median age of this patient group of 32 males
      and 5 females was 57 years (13-84years). The stage remained the same in 18 cases,
      decreased in 5 cases and increased in 14 cases with PET/CT imaging. Total gross
      tumor volume (GTV) determined by CT (GTVCT-Total) was increased in 32 cases
      (86.5%) when compared to total GTV determined by PET/CT (GTVPET/CT-Total). The
      GTV of the primary tumor determined by PET/CT (GTVPET/CT) was larger in 3 cases
      and smaller in 34 cases compared to that determined by CT (GTVCT). The GTV of
      lymph nodes determined by PET/CT (GTVLNPET/CT) was larger in 20 cases (54%) and
      smaller in 12 cases (32.5%) when compared to GTV values determined by CT
      (GTVLNCT). No pathological lymph nodes were observed in the remaining five cases
      with both CT and PET/ CT. CONCLUSIONS: We can conclude that PET/CT can
      significantly affect both pretreatment staging and assessed target tumor volume
      in patients with head and neck cancer. We therefore recommend examining such
      cases with PEC/CT before treatment.

PMID- 25605199
TI  - Diagnostic value of thyroglobulin measurement with fine-needle aspiration biopsy
      for lymph node metastases in patients with a history of differentiated thyroid
      cancer.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic value of FNA-Tg for
      detecting lymph node metastases in patients with a history of differentiated
      thyroid cancer (DTC). MATERIALS AND METHODS: A total of 58 patients with DTC
      diagnosis and evidence of single or multiple suspicious cervical lymph nodes were
      assessed. All underwent total or near-total thyroidectomy with (35 cases) or
      without (23 cases) radioiodine (RAI) ablation, followed by thyroid stimulating
      hormone (TSH) suppression therapy. A total of 68 lymph nodes were examined by
      ultrasound-guided fine needle aspiration (US-FNA) for both cytological
      examination and FNA-Tg measurement. Serum Tg and anti-thyroglobulin antibody
      (TgAb) levels were also measured. Diagnostic performance including sensitivity,
      specificity, accuracy, positive (PPV) and negative predictive value (NPV) of FNAC
      and FNA-Tg were calculated and compared. The Spearman's rank correlation
      coefficient was used to estimate the relationship between FNA-Tg and serum TgAb.
      RESULTS: The FNA-Tg levels were significantly higher with DTC metastatic lymph
      nodes (median 927.7 ng/mL, interquartile range 602.9 ng/mL) than non-metastatic
      lymph nodes (median 0.1 ng/mL, interquartile range 0.4 ng/mL) (p<0.01).
      Considering 1.0 ng/mL as a threshold value for FNA-Tg, the sensitivity,
      specificity, accuracy, PPV and NPV of FNA-Tg were 95.7%, 95.5%, 95.6%, 97.8% and
      91.3%, respectively. The sensitivity and accuracy of the combination of FNAC and
      FNA-Tg were significantly higher than that of FNAC alone (p<0.05). The diagnostic
      performance of FNA-Tg was not significantly different between cases with or
      without RAI ablation, and the serum TgAb levels did not interfere with FNA-Tg
      measurements. CONCLUSIONS: Measurement of FNA-Tg is useful. The combination of
      FNAC and FNA-Tg is more sensitive and accurate for detecting lymph node
      metastases in patients with a history of DTC than FNAC alone. Serum TgAbs appear
      to be irrelevant for measurement of FNA-Tg.

PMID- 25605201
TI  - DEP domain containing 1 is a novel diagnostic marker and prognostic predictor for
      hepatocellular carcinoma.
AB  - BACKGROUND: This study was conducted to determine DEPDC1 expression in
      hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and
      prognosis of affected patients. MATERIALS AND METHODS: DEPDC1 expression at the
      mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of
      HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in
      20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank
      test. Independent predictors associated with regard to disease free survival
      (DFS) and overall survival (OS) were identified using the Cox proportional hazard
      model. RESULTS: High DEPDC1 mRNA levels were detected in 144 out of 205 cases
      (70.24%) of HCC, significantly associated with clinicopathological parameters,
      including tumor size (>=4cm), alpha-fetoprotein (>=100ng/ml), B-C of BCLC stage
      and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with
      high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated
      that high DEPDC1 expression was an independent predictor of OS (HR=1.651; 95%
      95%CI, 1.041- 2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01- 2.483; p=0.045).
      CONCLUSIONS: Our results indicate DEPDC1 might be a novel diagnostic marker and
      an independent prognostic predictor for HCC patients.

PMID- 25605200
TI  - Steroidal saponins from Paris polyphylla suppress adhesion, migration and
      invasion of human lung cancer A549 cells via down-regulating MMP-2 and MMP-9.
AB  - BACKGROUND: Tumor metastases are the main reasons for oncotherapy failure. Paris
      polyphylla (Chinese name: Chonglou) has traditionally been used for its anti
      cancer actions. In this article, we focus on the regulation of human lung cancer
      A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS).
      MATERIALS AND METHODS: Cell viability was evaluated in A549 cells by MTT assay.
      Effects of PPSS on invasion and migration were investigated by wound-healing and
      matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was
      evaluated by MTT assay. Expression and protease activity of two matrix
      metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and
      gelatin zymography, respectively. RESULTS: PPSS exerted growth inhibitory effects
      on A549 cells, and effectively inhibited A549 cell adhesion, migration and
      invasion in a concentration-dependent manner. Western blotting and gelatin
      zymography analysis revealed that PPSS inhibited the expression and secretion of
      MMP-2 and MMP-9 in A549 cells. CONCLUSIONS: PPSS has the potential to suppress
      the migration, adhesion and invasion of A549 cells. PPSS could be a potential
      candidate for interventions against lung cancer metastases.

PMID- 25605202
TI  - Comparative histopathological characterization of prostate cancer in Saudi
      patients by conventional and 2005 ISUP modified gleason systems.
AB  - BACKGROUND: The aim of this study was to compare the characterization of prostate
      cancer using the conventional and 2005 ISUP modified Gleason systems. MATERIALS
      AND METHODS: The study employed samples from 40 prostate cancer patients with
      resection, biopsy and RP materials. The majority of cases (95%) comprised
      adenocarcinoma of the prostate with a modified combined Gleason score of 7 in 20
      of the cases (50%). RESULTS: Upgrading of Gleason scores to a score of 7 occurred
      in more than 45% of the cases. CONCLUSION: The study successfully showed that by
      the use of the 2005 ISUP modified Gleason system, score 6 cancers decreased from
      25% to 17.5% of cases, whereas score 7 cancers increased from 45% to 50%.

PMID- 25605203
TI  - Predictors of cancer awareness among older adult individuals in Jordan.
AB  - BACKGROUND: Older age is associated with an increase in the incidence of cancer
      cases. Diagnosis and treatment of cancer in older adults can be stressful because
      of health decline related to age, comorbidities and inadequate treatment for pain
      and other symptoms of the disease. This survey is one of the unique studies in
      Jordan and in the Arab world that aimed at exploring the predictors of older
      adult individuals awareness towards cancer. MATERIALS AND METHODS: A stratified
      random sampling technique was followed to reach a representative sample of 753
      participants. The questionnaire of the study consisted of parts regarding
      demographic variables, awareness about screening tests, and signs and symptoms of
      cancer. In addition, specific questions related to factors linked to cancer were
      included. Cross-sectional design was adopted with face-to-face interviews at the
      interviewees' households. RESULTS: The mean age of the participants was about 63
      years; around 44% of them are above the age of 65 years. 'Being convinced that
      having no health problem makes the individual feel safe and not at risk of
      getting cancer' was the major reason for not doing a routine health check-up.
      CONCLUSIONS: The low levels of awareness about cancer, as well as the low use of
      the screening methods were crucial outcomes of this study. Thus, raising the
      awareness among health care providers and policy makers in the country about
      older adults' perception of cancer is a high priority.

PMID- 25605204
TI  - Candida non albicans with a High amphotericin B resistance pattern causing
      candidemia among cancer patients.
AB  - BACKGROUND: Many scientists have reported Candida species to be of great concern
      because of the high frequency that they colonize and infect human hosts,
      particularly cancer patients. Moreover, in the last decades Candida species have
      developed resistance to many antifungal agents. Based on this, we aimed to
      identify and determine the prevalence of Candida spp from blood culture bottles
      among cancer patients and their antifungal resistance pattern. MATERIALS AND
      METHODS: From the blood culture bottles isolation and identification of the
      Candida spp were performed by conventional microbiological techniques. The in
      vitro antibiotic resistance pattern of the isolates was determined by CLSI
      guidelines. Genomic DNA was isolated and amplified. Each gene was separated by
      agar gel electrophoresis. RESULTS: Identification of Candida spp was based on the
      presence of yeast cells in direct examination, culture and DNA extraction. Of the
      68 blood samples collected during the study period (April 2013 to October 2013),
      five (7.35%) were positive for the presence of Candida spp, 2 (40%) of which were
      identified as Candida albicans and 3 (60%) were Candida non-albicans.
      CONCLUSIONS: High resistance to amphotricin B was observed among all the Candida
      non-albicans isolates. Regular investigations into antifungal resistance will
      help us to get an updated knowledge about their antibiotic resistance pattern
      which may help the physician in selecting the antibiotics for empirical therapy.

PMID- 25605206
TI  - Correlation study of knowledge and behavior regarding breast care among female
      undergraduate students in China.
AB  - BACKGROUND: This study aimed to understand the relationship between knowledge
      level and behavior on breast care in Chinese students, so as to provide
      strategies for improving the health education of breast care and subsequently for
      aiding in breast cancer prevention. MATERIALS AND METHODS: A self-designed
      questionnaire was used to evaluate breast care knowledge level and characterize
      related behavior. Correlation analysis was conducted for the knowledge level and
      behavior. The study was carried out using 597 female undergraduate students in
      medical and non-medical colleges in Wuhu, China. RESULTS: The average score of
      breast care knowledge was 5.32+/-1.68 (5.62+/-1.68 and 5.00+/-1.68 for medical
      and non-medical students, respectively), with a greater score value for
      sophomores (5.59+/-1.72) than freshmen (5.18+/-1.65). The average score of breast
      care behavior was 2.21+/-1.13, again with a greater value in sophomores (2.37+/
      1.15) than freshmen (2.21+/-1.13). A significant positive correlation (r=0.231,
      p<0.01) between knowledge scores and behavior scores was observed. In addition,
      various factors, including paying attention to breast care information, receiving
      breast self-examination guidance, TV program and Internet, were found to
      influence breast care knowledge. CONCLUSIONS: In general, female undergraduate
      students lack of self-awareness of breast care with a low rate of breast self
      examination. It is necessary to carry out health education to improve early
      detection of breast cancer.

PMID- 25605205
TI  - Association of methylation of the RAR-beta gene with cigarette smoking in non
      small cell lung cancer with Southern-Central Chinese population.
AB  - Pathogenesis of lung cancer is a complicated biological process including
      multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as
      the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this
      study was to determine whether tobacco exposure plays a role in gene methylation.
      Methylation of the RAR-beta gene were detected using methylation-specific
      polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and
      corresponding 105 controls. A significant statistical association was found in
      the detection rate of the promoter methylation of RAR-beta gene between NSCLC and
      controls (x2=166.01; p<0.01), and hypermethylation of the RAR-beta gene was
      significantly associated with smoking status (p=0.038, p<0.05). No relationship
      was found between RAR-beta gene methylation and pathologic staging including
      clinical stage, cell type, gender and drinking (p>0.05), and the methylation of
      RAR-beta gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in
      I+II (70.8%). Similar results were obtained for methylation of the RAR-beta gene
      between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%).
      These results showed that the frequency of methylation increased gradually with
      the development of clinical stage in smoking-associated lung cancer patients, and
      tobacco smoke may be play a potential role in RAR-beta gene methylation in the
      early pathogenesis and process in lung cancer, particularly squamous cell
      carcinoma. Aberrant promoter methylation is considered to be a promising marker
      of previous carcinogen exposure and cancer risk. 

PMID- 25605207
TI  - Asparagus polysaccharide and gum with hepatic artery embolization induces tumor
      growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.
AB  - Liver cancer is one of leading digestive malignancies with high morbidity and
      mortality. There is an urgent need for the development of novel therapies for
      this deadly disease. It has been proven that asparagus polysaccharide, one of the
      most active derivates from the traditional medicine asparagus, possesses notable
      antitumor properties. However, little is known about the efficacy of asparagus
      polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported
      that asparagus polysaccharide and its embolic agent form, asparagus gum,
      significantly inhibited liver tumor growth with transcatheter arterial
      chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC)
      tumor model, while significantly inhibiting angiogenesis and promoting tumor cell
      apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions
      and showed little toxicity to the host. These results highlight the
      chemotherapeutic potential of asparagus polysaccharide and warrant a future focus
      on development as novel chemotherapeutic agent for liver cancer TACE therapy. 

PMID- 25605208
TI  - Effects of the CYP2C19 genetic polymorphism on gastritis, peptic ulcer disease,
      peptic ulcer bleeding and gastric cancer.
AB  - BACKGROUND: The CYP2C19 genotype has been found to be an important factor for
      peptic ulcer healing and H. pylori eradication, influencing the efficacy of
      proton pump inhibitors (PPIs) and the pathogenesis of gastric cancer. The aim of
      this study was to investigate clinical correlations of the CYP2C19 genotype in
      patients with gastritis, peptic ulcer disease (PUD), peptic ulcer bleeding (PUB)
      and gastric cancer in Thailand. MATERIALS AND METHODS: Clinical information,
      endoscopic findings and H. pylori infection status of patients were assessed
      between May 2012 and November 2014 in Thammasat University Hospital, Thailand.
      Upper GI endoscopy was performed for all patients. Five milliliters of blood were
      collected for H. pylori serological diagnosis and CYP2C19 study. CYP2C19
      genotypes were determined by polymerase chain reaction (PCR) and restriction
      fragment length polymorphism analysis (RFLP) and classified as rapid metabolizer
      (RM), intermediate metabolizer (IM) or poor metabolizer (PM). RESULTS: A total of
      202 patients were enrolled including 114 with gastritis, 36 with PUD, 50 with PUB
      and 2 with gastric cancer. Prevalence of CYP2C19 genotype was 82/202 (40.6%) in
      RM, 99/202 (49%) in IM and 21/202 (10.4%) in PM. Overall H. pylori infection was
      138/202 patients (68.3%). H. pylori infection was demonstrated in 72% in RM
      genotype, 69.7% in IM genotype and 47.6% in PM genotype. Both gastric cancer
      patients had the IM genotype. In PUB patients, the prevalence of genotype RM
      (56%) was highest followed by IM (32%) and PM(12%). Furthermore, the prevalence
      of genotype RM in PUB was significantly greater than gastritis patients (56% vs
      36%: p=0.016; OR=2.3, 95%CI=1.1-4.7). CONCLUSIONS: CYP2C19 genotype IM was the
      most common genotype whereas genotype RM was the most common in PUB patients. All
      gastric cancer patients had genotype IM. The CYP2C19 genotype RM might be play
      role in development of PUD and PUB. Further study in different population is
      necessary to verify clinical usefulness of CYP2C19 genotyping in development of
      these upper GI diseases.

PMID- 25605209
TI  - Performance of HPV DNA testing with hybrid capture 2 in triaging women with minor
      cervical cytologic abnormalities (ASC-US/LSIL) in Northern Thailand.
AB  - BACKGROUND: Minor cervical cytologic abnormalities include atypical squamous
      cells of undetermined significance (ASC-US) and low-grade squamous
      intraepithelial lesion (LSIL). Approximately 10-20% of women with minor cytologic
      abnormalities have histologic high-grade squamous intraepithelial or worse
      lesions (HSIL+). In Thailand, women with minor cytologic abnormalities have a
      relatively high risk of cervical cancer, and referral for colposcopy has been
      suggested. A triage test is useful in the selection of women at risk for
      histologic HSIL+ to reduce the colposcopy burden. The aim of this study was to
      assess the performance of high-risk HPV DNA test in triage of women with minor
      cytologic abnormalities in northern Thailand. MATERIALS AND METHODS: All women
      with ASC-US/LSIL cytology who were referred to our colposcopy clinic from October
      2010 to February 2014 were included. HPV DNA testing was performed using Hybrid
      Capture 2 (HC2). All patients received colposcopic examination. Accuracy values
      of HC2 in predicting the presence of histologic HSIL+ were calculated. RESULTS:
      There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity
      rate was significantly higher in the LSIL group than in ASC-US group (74.8%
      versus 41.0%, p<0.001). Histologic HSIL+ was detected in 9 women (7.4%) in the
      ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was no
      histologic HSIL+ detected among HC2-negative cases (sensitivity and negative
      predictive value of 100%). The performance of HC2 triage was highest among women
      aged >50 years with ASC-US cytology. An increase in the cut-off threshold for
      positive HC2 resulted in a substantial decrease of sensitivity and negative
      predictive value. CONCLUSIONS: HPV DNA testing with HC2 shows very high
      sensitivity and negative predictive value in triage of women with minor cervical
      cytologic abnormalities in northern Thailand. An increase of the cut-off
      threshold for HC2 triage is not recommended in this region.

PMID- 25605210
TI  - Efficacy and survival-associated factors with gefitinib combined with cisplatin
      and gemcitabine for advanced non- small cell lung cancer.
AB  - OBJECTIVE: To analyze the efficacy and survival associated factors of gefitinib
      combined with cisplatin and gemcitabine for advanced non-small cell lung cancer.
      MATERIALS AND METHODS: A total of 57 patients with advanced non-small cell lung
      cancer (NSCLC), who received platinum-based chemotherapy regimens for more than 1
      cycle, were treated with gefitinib combined with cisplatin and gemcitabine until
      disease progression. Efficacy, survival time and adverse reactions were observed.
      The Kaplan-Meier method was adopted for analysis of survival and Cox regression
      for associated influencing factors. RESULTS: The patients were followed up until
      October 31, 2013, and the median follow-up time was 19 months. Of 57 patients,
      there were 4 (7.0%) with complete remission (CR), 8 (14.0%) with partial
      remission, 31 (54.4%) with stable disease, and 14 (24.6%) with disease
      progression. The remission rate was 21.1% and the disease control rate was 75.4%.
      The median progression-free survival (PFS) time and the median overall survival
      time were 10 months and 15.2 months. The one-year, two-year and three- year
      survival rates were 47.4%, 23.3% and 10.0%. Gender and pathological types were
      the independent risk factors influencing PFS time (P=0.028, P=0.009). Tumor
      pathological type and early efficacy were independent factors for the prognosis
      (P=0.018, P=0.000). Adverse reactions were mostly rashes of I~II degree and
      diarrhea and slightly increasing level of aminopherase. The skin adverse event
      incidence of III degree or above was 1.8% (1/57) and brain metastasis was foudn
      in 31.6% (18/57). CONCLUSIONS: Gefitinib combined with cisplatin andgemcitabine,
      is effective for patients with IIIb~IV NSCLC who received multiple cycles of
      chemotherapy.

PMID- 25605211
TI  - Effect of laparoscopic nerve-sparing radical hysterectomy on bladder function,
      intestinal function recovery and quality of sexual life in patients with cervical
      carcinoma.
AB  - OBJECTIVE: To investigate bladder and intestinal function recovery and quality of
      sexual life after laparoscopic nerve-sparing radical hysterectomy (LNRH) for
      treatment of early invasive cervical carcinoma. METHODS: Subjects included
      patients who underwent radical hysterectomy by laparotomy who were randomly
      assigned to 2 groups: 30 patients who underwent LNRH and 35 classical
      laparoscopic radical hysterectomy (LRH). We assessed the patients general
      clinical information, surgical characteristics, pathological findings, and
      adjuvant therapies. A urodynamic study was used to assess bladder function.
      Intestinal function recovery and quality of sexual life were evaluated by
      questionnaire. RESULTS: No significant differences were found in age, surgery
      characteristics, pathological findings, adjuvant therapies, and main adverse
      effects between the 2 groups. The mean duration of the postoperative
      catheterization (DPC) in group LNRH was shorter than that in group LRH (P <
      0.001). The maximum flow rate, maximum cystometric capacity , maximum detrusor
      pressure and urinary complications in group LNRH were better than those in group
      LRH. The quality of sexual life evaluated according to the female sexual function
      index (FSFI) was better in group LNRH than in those who underwent LRH. The
      intestinal function of patients in group LNRH also recovered better compared with
      patients in group LRH.

PMID- 25605212
TI  - Cantharidin combined with chemotherapy for Chinese patients with metastatic
      colorectal cancer.
AB  - BACKGROUND: This systematic analysis was conducted to evaluate the efficacy and
      safety of cantharidin combined with chemotherapy in treating Chinese patients
      with metastatic colorectal cancer. METHODS: Clinical studies evaluating the
      efficacy and safety of cantharidin combined with chemotherapy on response and
      safety for Chinese patients with colorectal cancer were identified using a
      predefined search strategy. Pooled response rate (RR) of treatment were
      calculated. RESULTS: When cantharidin combined with chemotherapy, 4 clinical
      studies which included 155 patients with advanced colorectal cancer were
      considered eligible for inclusion. The systematic analysis suggested that, in all
      patients, pooled RR was 46.5% (72/155) in cantharidin combined regimens. Major
      adverse effects were neutropenia, leukopenia, fatigue, and anemia with
      cantharidin combined treatment; no treatment related deaths occurred. CONCLUSION:
      This systematic analysis suggests that cantharidin combined regimens are
      associated with high response rate and accepted toxicity in treating Chinese
      patients with metastatic colorectal cancer suggesting that randomized clinical
      trials are now warranted.

PMID- 25605213
TI  - Prevalence of esophageal cancer in the Northern part of Afghanistan.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) is the standard technique for
      diagnosis of patients presenting with upper gastrointestinal symptoms. Some
      reports have shown high prevalence of esophageal cancer in the northern part of
      Afghanistan. The aim of this study was to investigate epidemiological profile of
      esophageal cancer among patients in this region. MATERIALS AND METHODS: We
      identified 364 consecutive patients that received EGD examinations to examine
      upper gastrointestinal tract at the endoscopy unit of Balkh regional Hospital
      from March 2012 to March 2013. The case subjects included both in-patients and
      out-patients aged 16 years or more. We evaluated the results retrospectively.
      RESULTS: The cases consisted of 184 (51%) males and 180 (49%) females. The mean
      age was 47.3+/-17.8 and the age range 17-88 years. Ninety two cases had
      esophageal cancer, out of which 58 (63.0%) were male. The mean age at time of
      diagnosis was 57.8+/-13.2 years. Uzbek-Turkmen peoples were more common among
      patients with esophageal cancer (52.2%). Dysphagia was the most frequent symptom
      among patients with esophageal cancer at the time of presentation, seen in 77
      (84.8%) of cases. CONCLUSIONS: Our results showed high incidence of esophageal
      cancer in the northern part of Afghanistan, especially in the Uzbek-Turkmen
      ethnic group.

PMID- 25605214
TI  - DNA ligase4 as a prognostic marker in nasopharyngeal cancer patients treated with
      radiotherapy.
AB  - BACKGROUND: The capability for DNA double-strand breaks (DSBs) repair is crucial
      for inherent radiosensitivity of tumor and normal cells. We have investigated the
      clinicopathologic significance of DNA repair gene expression in nasopharyngeal
      (NP) carcinoma. MATERIALS AND METHODS: A total of 65 NP cancer patients who
      received radiotherapy were included. The immunopositivity to Ku 70, DNA-PKcs,
      MRN, RAD50, XRCC4, and LIG4 were examined in all tumor tissues. RESULTS: The
      patients comprised 42 males and 23 females, with a median age of 56 years (range,
      18-84). The expression levels of RAD50 (0,+1,+2,+3) were 27.7%, 32.3%, 21.5%, and
      18.5%. LIG4 (+/-) were 43.1% and 56.9% respectively. The 5-year OS rate of
      patients with LIG4 (+/-) were 90% and 67.9%, respectively (p=0.035). The 5-year
      TTP rate of patients with LIG4 (+/-) were 75.9%, 55.5%, respectively (P=0.039).
      CONCLUSIONS: Our results suggest the possibility of predicting the
      radiosensitivity of NP cancer by performing immunohistochemical analysis of LIG4.

PMID- 25605215
TI  - Pan masala plus tobacco is equal to Gutka square--new formulation of tobacco in
      India after the Gutka ban.
AB  - Tobacco is a well known cause of death worldwide. With existing comprehensive
      laws and various other measures for tobacco control, the mortality and morbidity
      due to tobacco usage have unfortunately not been reduced. A large number of
      tobacco users have altered their pattern of tobacco use after the gutka ban.
      Traditional gutka is sold in the open market in a pre-mixed format. Manufacturers
      are supplying pan masala and tobacco in separate pouches as there is no
      restriction for sale of pan masala and tobacco individually in many states.
      Although most of the population is aware of the health hazards of tobacco, it is
      necessary to develop an effective structured strategy. Tobacco control programs
      need to be strengthened by separate tobacco control measures at various levels. 

PMID- 25605216
TI  - Substance P is a major mediator causing delayed emesis in anthracycline-based
      chemotherapy--really?

PMID- 25605217
TI  - Survival outcome of AML patients with and without TKD mutations.

PMID- 25605218
TI  - Expectations of response from octreotide therapy in recurrent phosphaturic
      mesenchymal tumors--do they reflect reality?

PMID- 25605219
TI  - Thyroid autoantibodies and breast cancer.

PMID- 25605220
TI  - Gestational diabetes mellitus and subsequent cancer risk: shared risk factors,
      causality or confounding?

PMID- 25605221
TI  - The technique of sacral nerve modulation.
AB  - AIM: The aim of this review was to summarize current knowledge and
      recommendations regarding the technique of implantation of the electrode in
      performing sacroneuromodulation (SNM) and the available information on
      programming parameters and implantation algorithms. METHOD: All English-language
      articles published from January 1985 to December 2013 that reported the SNM
      surgical technique and results were considered for inclusion. Data were
      considered useful for the present review only if related to: (i) peripheral nerve
      evaluation; (ii) temporary nerve stimulation; (iii) definitive impulse generator
      placement; and (iv) parameters programming. RESULTS: The literature search
      revealed 193 potentially relevant studies from initial electronic search terms
      and eligibility criteria, and these studies were evaluated in detail. In total,
      41 studies were included in the final analysis. Of the studies reviewed, the
      majority (n = 37) were prospective or retrospective case series. Only three
      randomized clinical trials were eligible for inclusion. CONCLUSION: Although the
      technique seems to be standardized, several steps still need to be clarified in
      order to define the best way to perform the procedure and then to maximize the
      outcome.

PMID- 25605222
TI  - Field assessment of dried Plasmodium falciparum samples for malaria rapid
      diagnostic test quality control and proficiency testing in Ethiopia.
AB  - BACKGROUND: Rapid diagnostic tests (RDTs) are now widely used for laboratory
      confirmation of suspected malaria cases to comply with the World Health
      Organization recommendation for universal testing before treatment. However, many
      malaria programmes lack quality control (QC) processes to assess RDT use under
      field conditions. Prior research showed the feasibility of using the dried tube
      specimen (DTS) method for preserving Plasmodium falciparum parasites for use as
      QC samples for RDTs. This study focused on the use of DTS for RDT QC and
      proficiency testing under field conditions. METHODS: DTS were prepared using
      cultured P. falciparum at densities of 500 and 1,000 parasites/MUL; 50 MUL
      aliquots of these along with parasite negative human blood controls (0
      parasites/MUL) were air-dried in specimen tubes and reactivity verified after
      rehydration. The DTS were used in a field study in the Oromia Region of Ethiopia.
      Replicate DTS samples containing 0, 500 and 1,000 parasites/MUL were stored at 4
      degrees C at a reference laboratory and at ambient temperatures at two nearby
      health facilities. At weeks 0, 4, 8, 12, 16, 20, and 24, the DTS were rehydrated
      and tested on RDTs stored under manufacturer-recommended temperatures at the RL
      and on RDTs stored under site-specific conditions at the two health facilities.
      Reactivity of DTS stored at 4 degrees C at the reference laboratory on RDTs
      stored at the reference laboratory was considered the gold standard for assessing
      DTS stability. A proficiency-testing panel consisting of one negative and three
      positive samples, monitored with a checklist was administered at weeks 12 and 24.
      RESULTS: At all the seven time points, DTS stored at both the reference
      laboratory and health facility were reactive on RDTs stored under the recommended
      temperature and under field conditions, and the DTS without malaria parasites
      were negative. At the reference laboratory and one health facility, a 500
      parasites/MUL DTS from the proficiency panel was falsely reported as negative at
      week 24 due to errors in interpreting faint test lines. CONCLUSIONS: The DTS
      method can be used under field conditions to supplement other RDT QC methods and
      health worker proficiency in Ethiopia and possibly other malaria-endemic
      countries.

PMID- 25605223
TI  - Ecology and evolution of floral volatile-mediated information transfer in plants.
AB  - Floral volatiles are complex, multi-functional signals that are often used by
      pollinators in combination with other signals, such as color. Floral visitors use
      floral scent to estimate the amount of reward present in flowers, to facilitate
      the identification of a specific host flower or as signals that chemically
      resemble those important for pollinator insects in other ecological contexts.
      There is good evidence that floral scent evolves under selection imposed by both
      mutualists and antagonists. Antagonists may often limit the amount of scent
      emitted by flowers, thus contributing to spatial population variation, and select
      for phenotypic plasticity after enemy attack. Floral scent is also an important
      component of pollinator-mediated reproductive isolation, as it often co-varies
      with color and morphology in sister species with different pollination systems.

PMID- 25605224
TI  - Production of three-dimensional quantum dot lattice of Ge/Si core-shell quantum
      dots and Si/Ge layers in an alumina glass matrix.
AB  - We report on the formation of Ge/Si quantum dots with core/shell structure that
      are arranged in a three-dimensional body centered tetragonal quantum dot lattice
      in an amorphous alumina matrix. The material is prepared by magnetron sputtering
      deposition of Al2O3/Ge/Si multilayer. The inversion of Ge and Si in the
      deposition sequence results in the formation of thin Si/Ge layers instead of the
      dots. Both materials show an atomically sharp interface between the Ge and Si
      parts of the dots and layers. They have an amorphous internal structure that can
      be crystallized by an annealing treatment. The light absorption properties of
      these complex materials are significantly different compared to films that form
      quantum dot lattices of the pure Ge, Si or a solid solution of GeSi. They show a
      strong narrow absorption peak that characterizes a type II confinement in
      accordance with theoretical predictions. The prepared materials are promising for
      application in quantum dot solar cells. 

PMID- 25605226
TI  - High-gain and low-driving-voltage photodetectors based on organolead triiodide
      perovskites.

PMID- 25605225
TI  - Non-invasive sensitive detection of KRAS and BRAF mutation in circulating tumor
      cells of colorectal cancer patients.
AB  - Characterization of genetic alterations in tumor biopsies serves as useful
      biomarkers in prognosis and treatment management. Circulating tumor cells (CTCs)
      obtained non-invasively from peripheral blood could serve as a tumor proxy. Using
      a label-free CTC enrichment strategy that we have established, we aimed to
      develop sensitive assays for qualitative assessment of tumor genotype in
      patients. Blood consecutively obtained from 44 patients with local and advanced
      colorectal cancer and 18 healthy donors were enriched for CTCs using a size-based
      microsieve technology. To screen for CTC mutations, we established high
      resolution melt (HRM) and allele-specific PCR (ASPCR) KRAS-codon 12/13- and BRAF
      codon 600- specific assays, and compared the performance with pyrosequencing and
      Sanger sequencing. For each patient, the resulting CTC genotypes were compared
      with matched tumor and normal tissues. Both HRM and ASPCR could detect as low as
      1.25% KRAS- or BRAF-mutant alleles. HRM detected 14/44 (31.8%) patients with KRAS
      mutation in CTCs and 5/44 (11.3%) patients having BRAF mutation in CTCs. ASPCR
      detected KRAS and BRAF mutations in CTCs of 10/44 (22.7%) and 1/44 (2.3%)
      patients respectively. There was an increased detection of mutation in blood
      using these two methods. Comparing tumor tissues and CTCs mutation status using
      HRM, we observed 84.1% concordance in KRAS genotype (p = 0.000129, Fishers' exact
      test; OR = 38.7, 95% CI = 4.05-369) and 90.9% (p = 0.174) concordance in BRAF
      genotype. Our results demonstrate that CTC enrichment, coupled with sensitive
      mutation detection methods, may allow rapid, sensitive and non-invasive
      assessment of tumor genotype.

PMID- 25605227
TI  - Determination of N,N-dimethyldodecylamine and N,N-dimethyloctadecylamine in river
      and sea water using liquid chromatography tandem mass spectrometry.
AB  - We developed a selective method for determining N,N-dimethyldodecylamine (DMDA)
      and N,N-dimethyloctadecylamine (DMOA) concentrations in river and sea water
      samples using liquid chromatography/tandem mass spectrometry (LC/MS/MS). DMDA and
      DMOA are suspected to be toxic, and DMDA is categorized as a "Class I Designated
      Chemical Substance" under the "Act on Confirmation, etc. of Release Amounts of
      Specific Chemical Substances in the Environment and Promotion of Improvements to
      the Management Thereof" in Japan. The analytes are extracted from a water sample
      using solid phase extraction and the extract is evaporated and dissolved in 1 mL
      methanol for LC/MS/MS analysis. We analyzed DMDA and DMOA in real water samples
      and found that the analyte peaks were resolved effectively. The method detection
      limits for DMDA and DMOA were 4.7 and 0.80 ng/L, respectively. 

PMID- 25605228
TI  - Methylation of the CTLA-4 promoter and Treg cell dysfunction in rheumatoid
      arthritis: comment on the article by Cribbs et al.

PMID- 25605229
TI  - Mixed mode of dissolving immersed nanodroplets at a solid-water interface.
AB  - The dissolution dynamics of microscopic oil droplets (less than 1 MUm in height,
      i.e. nanodroplets) on a hydrophobilized silicon surface in water was
      experimentally studied. The lateral diameter was monitored using confocal
      microscopy, whereas the contact angle was measured by (disruptive) droplet
      polymerisation of the droplet. In general, we observed the droplets to dissolve
      in a mixed mode, i.e., neither in the constant contact angle mode nor in the
      constant contact radius mode. This means that both the lateral diameter and the
      contact angle of the nanodroplets decrease during the dissolution process. On
      average, the dissolution rate is faster for droplets with larger initial size.
      Droplets with the same initial size can, however, possess different dissolution
      rates. We ascribe the non-universal dissolution rates to chemical and geometric
      surface heterogeneities (that lead to contact line pinning) and cooperative
      effects from the mass exchange among neighbouring droplets. 

PMID- 25605230
TI  - Congenital anomalies of the kidney and urinary tract genetics in mice and men.
AB  - The most common cause of paediatric end-stage kidney disease results from
      congenital anomalies of the kidney and urinary tract (CAKUT). Genetic
      manipulation in mice has provided insight into the developmental events that give
      rise to the broad spectrum of malformations associated with CAKUT. Despite the
      increase in the number of identified CAKUT-causing genes, the underlying genetic
      cause for the majority of patients with CAKUT remains unknown. In this mini
      review, we provide an overview of the genetic causes of CAKUT based on current
      mouse mutant models, as well as next-generation sequencing approaches in humans
      that are helping to bridge the gaps in our understanding. 

PMID- 25605231
TI  - Reproductive biology of the greeneye spurdog Squalus chloroculus (Squaliformes,
      Squalidae).
AB  - The reproduction of the greeneye spurdog Squalus chloroculus was studied based on
      animals caught in the multispecies and multi-gear southern and eastern scalefish
      and shark fishery on the upper continental slope off southern Australia. One
      hundred and ninety-nine females (502-990 mm, total length, LT ) and 189 males
      (515-810 mm LT ) were examined. The female reproductive cycle, based on 41
      breeding animals, is continuous and triennial, with the pregnancy period
      estimated to be 31-34 months, seasonal and synchronous with the ovarian cycle; a
      third of the breeding female population is estimated to give birth between
      September and December each year. The estimated LT at which 50% of females are
      mature is 799 mm (95% c.i.: 794, 804), whereas the LT at which 50% are maternal
      is 825 mm (95% c.i.: 817-833), but these estimates are probably biased by the
      phenomenon of apparent change of LT at maternity and LT at maturity following
      severe length-selective fishing mortality. Litters ranged from four to 15 embryos
      with a 1:1 sex ratio, and litter size increased with maternal length. The
      breeding cycle of males is neither seasonal nor synchronous with the female
      cycle. The estimated LT of males where 50% are mature was 629 mm (95% c.i.: 603,
      645).

PMID- 25605232
TI  - [Pain therapy in patients with schizoaffective disorder and cancer].
AB  - We report on two patients with schizoaffective psychosis, cancer, and pain.
      However, it is not possible to make somatic or psychic disturbances alone
      responsible for the pain. In patients with current schizoaffective disorders,
      only administration of a combination of psychopharmaceutical and opioid agents is
      successful. 

PMID- 25605234
TI  - Exercise: not a panacea.

PMID- 25605233
TI  - [Pain and pain-assessment in nursing homes : Results of the OSiA study].
AB  - BACKGROUND: Adequate and sufficient data on pain in nursing home residents is
      still lacking in Austria. This study intends to gather and increase available
      data on pain and pain assessment as well as identify potential improvement
      possibilities. STUDY PARTICIPANTS AND METHODS: Using a cross-sectional design,
      425 residents from 12 Austrian nursing homes were recruited. The selected homes
      were selected as a cluster sample from 29 homes operated by one carrier. Pain
      assessment of cognitively intact as well as cognitively impaired residents was
      conducted using questionnaires, observation, and medical record examination.
      RESULTS: Pain prevalence was dependent on type of resident and ranged between
      37.9 and 73.1 %. Sensitivity of the proxy assessment instruments varied between
      47.7 and 87.7 %. Overall, 81 % of residents with daily recurring pain have been
      pain sufferers for at least one year. Between 40 and 68 % do not disclose their
      pain or consider their pain as being a part of aging. CONCLUSION: Our data on
      pain indicate a definite need for action. Accurately detecting pain requires
      reliable and resident-adapted means of assessment. Varying prevalence,
      specificity, and sensitivity numbers indicate the need for further research.

PMID- 25605235
TI  - Role of Cys3602 in the function and regulation of the cardiac ryanodine receptor.
AB  - The cardiac Ca2+ release channel [ryanodine receptor type 2 (RyR2)] is modulated
      by thiol reactive agents, but the molecular basis of RyR2 modulation by thiol
      reagents is poorly understood. Cys3635 in the skeletal muscle RyR1 is one of the
      most hyper-reactive thiols and is important for the redox and calmodulin (CaM)
      regulation of the RyR1 channel. However, little is known about the role of the
      corresponding cysteine residue in RyR2 (Cys3602) in the function and regulation
      of the RyR2 channel. In the present study, we assessed the impact of mutating
      Cys3602 (C3602A) on store overload-induced Ca2+ release (SOICR) and the
      regulation of RyR2 by thiol reagents and CaM. We found that the C3602A mutation
      suppressed SOICR by raising the activation threshold and delayed the termination
      of Ca2+ release by reducing the termination threshold. As a result, C3602A
      markedly increased the fractional Ca2+ release. Furthermore, the C3602A mutation
      diminished the inhibitory effect of N-ethylmaleimide on Ca2+ release, but it had
      no effect on the stimulatory action of 4,4'-dithiodipyridine (DTDP) on Ca2+
      release. In addition, Cys3602 mutations (C3602A or C3602R) did not abolish the
      effect of CaM on Ca2+-release termination. Therefore, RyR2-Cys3602 is a major
      site mediating the action of thiol alkylating agent N-ethylmaleimide, but not the
      action of the oxidant DTDP. Our data also indicate that residue Cys3602 plays an
      important role in the activation and termination of Ca2+ release, but it is not
      essential for CaM regulation of RyR2.

PMID- 25605236
TI  - Three-dimensional computed tomographic evaluation of Le Fort III distraction
      osteogenesis with an external device in syndromic craniosynostosis.
AB  - There is little anteroposterior growth of the midface in patients with syndromic
      craniosynostosis who are followed up over time without intervention. A Le Fort
      III with distraction osteogenesis can be done to correct this. This is a
      controlled way in which to achieve appreciable stable advancement of the midface
      without the need for bone grafting, but the vector of the movement is not always
      predictable. The purpose of this study was to evaluate the 3-dimensional effect
      of Le Fort III distraction osteogenesis with an external frame. Ten patients
      (aged 7-19 years) who had the procedure were included in the study. The le Fort
      III procedure and the placement of the external frame were followed by an
      activation period and then a 3-month retention period. Computed tomographic (CT)
      images taken before and after operation were converted and loaded into 3
      dimensional image rendering software and compared with the aid of a paired sample
      t test and a colour-coded qualitative analysis. Comparison of the CT data before
      and after distraction indicated that the amount of midface advancement was
      significant. Le Fort III distraction osteogenesis is an effective way to advance
      the midface. However, the movement during osteogenesis is not always exactly in
      the intended direction, and a secondary operation is often necessary. Three
      dimensional evaluation over a longer period of time is necessary. 

PMID- 25605237
TI  - The genomic landscape of fibrolamellar hepatocellular carcinoma: whole genome
      sequencing of ten patients.
AB  - Fibrolamellar hepatocellular carcinoma is a rare, malignant liver tumor that
      often arises in the otherwise normal liver of adolescents and young adults.
      Previous studies have focused on biomarkers and comparisons to traditional
      hepatocellular carcinoma, and have yielded little data on the underlying
      pathophysiology. We performed whole genome sequencing on paired tumor and normal
      samples from 10 patients to identify recurrent mutations and structural
      variations that could predispose to oncogenesis. There are relatively few coding,
      somatic mutations in this cancer, putting it on the low end of the mutational
      spectrum. Aside from a previously described heterozygous deletion on chromosome
      19 that encodes for a functional, chimeric protein, there were no other recurrent
      structural variations that contribute to the tumor genotype. The lack of a second
      hit mutation in the genomic landscape of fibrolamellar hepatocellular carcinoma
      makes the DNAJB1-PRKACA fusion protein the best target for diagnostic and
      therapeutic advancements. The mutations, altered pathways and structural variants
      that characterized fibrolamellar hepatocellular carcinoma were distinct from
      those in hepatocellular carcinoma, further defining it as a distinct carcinoma. 

PMID- 25605238
TI  - Helicobacter pylori bacteria alter the p53 stress response via ERK-HDM2 pathway.
AB  - H. pylori infection is the strongest known risk factor for gastric cancer.
      Inhibition of host tumor suppressor mechanisms by the bacteria underlies the
      development of this disease. Among the tumor suppressors affected by H. pylori
      are p53 and E-cadherin, which inhibition has been shown to increase the risk of
      gastric cancer. In this report, we investigated the interaction between E
      cadherin and p53 in H. pylori-infected cells. We found that downregulation of E
      cadherin leads to cellular stress and activation of p53. In the setting of H.
      pylori infection, this mechanism, however, is disrupted. We found that although
      co-culture of gastric epithelial cells with H. pylori led to downregulation of E
      cadherin and cellular stress, it resulted in inhibition of p53, which is mediated
      by intracellular Erk kinases and HDM2 protein induced by H. pylori. Experimental
      inhibition of HDM2/p53 interactions restored p53 activity, and decreased survival
      of infected cells. Collectively, our results revealed that regulation of p53 and
      E-cadherin is tightly linked through the p53 stress response mechanism that is
      inhibited by H. pylori via activation of Erk1/2-HDM2-p53 pathway leading to
      survival of damaged cells. This might be advantageous to the bacteria but may
      increase the cancer risk. 

PMID- 25605239
TI  - Expression of the potential therapeutic target CXXC5 in primary acute myeloid
      leukemia cells - high expression is associated with adverse prognosis as well as
      altered intracellular signaling and transcriptional regulation.
AB  - The CXXC5 gene encodes a transcriptional activator with a zinc-finger domain, and
      high expression in human acute myeloid leukemia (AML) cells is associated with
      adverse prognosis. We now characterized the biological context of CXXC5
      expression in primary human AML cells. The global gene expression profile of AML
      cells derived from 48 consecutive patients was analyzed; cells with high and low
      CXXC5 expression then showed major differences with regard to extracellular
      communication and intracellular signaling. We observed significant differences in
      the phosphorylation status of several intracellular signaling mediators (CREB,
      PDK1, SRC, STAT1, p38, STAT3, rpS6) that are important for PI3K-Akt-mTOR
      signaling and/or transcriptional regulation. High CXXC5 expression was also
      associated with high mRNA expression of several stem cell-associated
      transcriptional regulators, the strongest associations being with WT1, GATA2,
      RUNX1, LYL1, DNMT3, SPI1, and MYB. Finally, CXXC5 knockdown in human AML cell
      lines caused significantly increased expression of the potential tumor suppressor
      gene TSC22 and genes encoding the growth factor receptor KIT, the cytokine
      Angiopoietin 1 and the selenium-containing glycoprotein Selenoprotein P. Thus,
      high CXXC5 expression seems to affect several steps in human leukemogenesis,
      including intracellular events as well as extracellular communication. 

PMID- 25605240
TI  - Hypoxia induces a lipogenic cancer cell phenotype via HIF1alpha-dependent and 
      independent pathways.
AB  - The biochemistry of cancer cells diverges significantly from normal cells as a
      result of a comprehensive reprogramming of metabolic pathways. A major factor
      influencing cancer metabolism is hypoxia, which is mediated by HIF1alpha and
      HIF2alpha. HIF1alpha represents one of the principal regulators of metabolism and
      energetic balance in cancer cells through its regulation of glycolysis, glycogen
      synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known
      about the role of HIF1alpha in modulating lipid metabolism. Lipids serve cancer
      cells to provide molecules acting as oncogenic signals, energetic reserve,
      precursors for new membrane synthesis and to balance redox biological reactions.
      To study the role of HIF1alpha in these processes, we used HCT116 colorectal
      cancer cells expressing endogenous HIF1alpha and cells in which the hif1alpha
      gene was deleted to characterize HIF1alpha-dependent and independent effects on
      hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with
      proteomics revealed that hypoxia induced many changes in lipids metabolites.
      Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in
      a HIF1alpha-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were
      regulated in a HIF-independent manner. Our results demonstrate the impact of
      hypoxia on lipid metabolites, of which a distinct subset is regulated by
      HIF1alpha. 

PMID- 25605241
TI  - DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition,
      focal adhesion, and stemness in clear cell renal carcinoma.
AB  - Renal clear cell carcinoma (RCC) is the most common type of kidney cancer and the
      8th most common cancer overall in the US. RCC survival rates drop precipitously
      with regional and distant spread and recent studies have demonstrated that RCC
      presents an epithelial-mesenchymal transition (EMT) phenotype linked to increased
      recurrence and decreased survival. EMT is a key characteristic of tumor stem
      cells (TSCs) along with chemo-resistance and radio-resistance, which are also
      phenotypic of RCC. Targeting these factors is key to increasing the survival of
      RCC patients. Doublecortin-like kinase 1 (DCLK1) marks TSCs in pancreatic and
      colorectal cancer and regulates EMT and stemness. Analysis of the Cancer Genome
      Atlas' RCC dataset revealed that DCLK1 is overexpressed and dysregulated on the
      mRNA and epigenetic level in more than 93% of RCC tumors relative to adjacent
      normal tissue. Immunohistochemistry using alpha-DCLK1 antibody confirmed
      overexpression and demonstrated a major increase in immunoreactivity in stage II
      III tumors compared to normal kidney and stage I tumors. Small-interfering RNA
      (siRNA) mediated knockdown of DCLK1 resulted in decreased expression of EMT and
      pluripotency factors and significantly reduced invasion, migration, focal
      adhesion, drug-resistance, and clonogenic capacity. These findings suggest that
      DCLK1 is a novel, overexpressed factor in RCC progression that may be targeted to
      suppress EMT, metastasis, and stemness in early-stage and advanced RCC to
      increase patient survival. Moreover, the possibility that DCLK1 may mark a
      population of tumor stem-like cells in RCC should be further investigated in
      light of these findings. 

PMID- 25605242
TI  - Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated
      activation of the Wnt/beta-catenin pathway.
AB  - Slit2 is often overexpressed in cancers. Slit2 is a secreted protein that binds
      to Roundabout (Robo) receptors to regulate cell growth and migration. Here, we
      employed several complementary mouse models of intestinal cancers, including the
      Slit2 transgenic mice, the ApcMin/+ spontaneous intestinal adenoma mouse model,
      and the DMH/DSS-induced colorectal carcinoma model to clarify function of
      Slit2/Robo1 signaling in intestinal tumorigenesis. We showed that Slit2 and Robo1
      are overexpressed in intestinal tumors and may contribute to tumor generation.
      The Slit2/Robo1 signaling can induce precancerous lesions of the intestine and
      tumor progression. Ectopic expression of Slit2 activated Slit2/Robo1 signaling
      and promoted tumorigenesis and tumor growth. This was mediated in part through
      activation of the Src signaling, which then down-regulated E-cadherin, thereby
      activating Wnt/beta-catenin signaling. Thus, Slit2/Robo1 signaling is oncogenic
      in intestinal tumorigenesis. 

PMID- 25605243
TI  - Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by
      regulating stemness factors and multidrug resistance factors.
AB  - MicroRNA-381 (miR-381) is a highly expressed onco-miRNA that is involved in
      malignant progression and has been suggested to be a good target for glioblastoma
      multiforme (GBM) therapy. In this study, we employed two-dimensional fluorescence
      differential gel electrophoresis (2-D DIGE) and MALDI-TOF/TOF-MS/MS to identify
      27 differentially expressed proteins, including the significantly upregulated
      neurofilament light polypeptide (NEFL), in glioblastoma cells in which miR-381
      expression was inhibited. We identified NEFL as a novel target molecule of miR
      381 and a tumor suppressor gene. In human astrocytoma clinical specimens, NEFL
      was downregulated with increased levels of miR-381 expression. Either suppressing
      miR-381 or enforcing NEFL expression dramatically sensitized glioblastoma cells
      to temozolomide (TMZ), a promising chemotherapeutic agent for treating GBMs. The
      mechanism by which these cells were sensitized to TMZ was investigated by
      inhibiting various multidrug resistance factors (ABCG2, ABCC3, and ABCC5) and
      stemness factors (ALDH1, CD44, CKIT, KLF4, Nanog, Nestin, and SOX2). Our results
      further demonstrated that miR-381 overexpression reversed the viability of U251
      cells exhibiting NEFL-mediated TMZ sensitivity. In addition, NEFL-siRNA also
      reversed the proliferation rate of U251 cells exhibiting locked nucleic acid
      (LNA)-anti-miR-381-mediated TMZ sensitivity. Overall, the miR-381-NEFL axis is
      important for TMZ resistance in GBM and may potentially serve as a novel
      therapeutic target for glioma. 

PMID- 25605244
TI  - MiR-125b regulates epithelial-mesenchymal transition via targeting Sema4C in
      paclitaxel-resistant breast cancer cells.
AB  - Emerging evidence has demonstrated that microRNAs (miRNA) play a critical role in
      chemotherapy-induced epithelial-mesenchymal transition (EMT) in breast cancer.
      However, the underlying mechanism of chemotherapy-mediated EMT has not been fully
      understood. To address this concern, we explored the role of miR-125b in
      regulation of EMT in stable paclitaxel-resistant (PR) breast cancer cells, namely
      MCF-7 PR and SKBR3 PR, which have displayed mesenchymal features. Our results
      illustrated that miR-125b was significantly downregulated in PR cells. Moreover,
      ectopic expression of miR-125b by its mimics reversed the phenotype of EMT in PR
      cells. Furthermore, we found that miR-125b governed PR-mediate EMT partly due to
      governing its target Sema4C. More importantly, overexpression of miR-125b or
      depletion of Sema4C sensitized PR cells to paclitaxel. These findings suggest
      that up-regulation of miR-125b or targeting Sema4C could serve as novel
      approaches to reverse chemotherapy resistance in breast cancers. 

PMID- 25605245
TI  - MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells.
AB  - Using miRNA microarray analysis, we identified 31 miRNAs that were significantly
      up-regulated or down-regulated in colon cancer tissues. We chose MIR196B, which
      was specifically up-regulated in colon cancer, for further study. We identified
      18 putative MIR196B target genes by comparing between the mRNAs down-regulated in
      MIR196B-overexpressed cells and the assumed MIR196B target genes predicted by
      public bioinformatics tools. The association between MIR196B and FAS was verified
      in this study. FAS expression was constitutively elevated in normal human
      colorectal tissues. However, its expression was often reduced in human colorectal
      cancer. The decrease in FAS expression could be responsible for the reduction of
      apoptosis in colorectal cancer cells. In colorectal cancer tissue, we showed that
      MIR196B up-regulation was mutually followed by down regulation of FAS expression.
      We also showed that MIR196B directly repressed FAS expression in colorectal
      cells. Furthermore, anti-MIR196B up-regulated FAS expression and increased
      apoptosis in colorectal cancer cell lines. Our results suggest that the up
      regulation of MIR196B modulates apoptosis in colorectal cancer cells by partially
      repressing FAS expression and that anti-MIR196B could be a potential candidate as
      an anti-cancer drug in colorectal cancer therapy. 

PMID- 25605246
TI  - NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses
      prostate cancer without adverse effect.
AB  - Herein, we investigated therapeutic potential of a novel histone lysine
      demethylase 1 (LSD1) inhibitor, NCL1, in prostate cancer. Hormone-sensitive
      prostate cancer cells, (LNCaP) and castration resistant cancer cells (PC3 and
      PCai1) were treated with NCL1, and LSD1 expression and cell viability were
      assessed. Prostate cancer cells showed strong LSD1 expression, and cell viability
      was decreased by NCL1. ChIP analysis showed that NCL1 induced H3K9me2
      accumulation at the promoters of androgen-responsive genes. NCL1 also induced G1
      cell cycle arrest and apoptosis. In addition, autophagosomes and autolysosomes
      were induced by NCL1 treatment in LNCaP. Furthermore, LC3-II expression was
      significantly increased by NCL1 and chloroquine. In mice injected subcutaneously
      with PCai1 and intraperitoneally with NCL1, tumor volume was reduced with no
      adverse effects in NCL1-treated mice. Finally, LSD1 expression in human cancer
      specimens was significantly higher than that in normal prostate glands. In
      conclusion, NCL1 effectively suppressed prostate cancer growth without adverse
      events. We suggest that NCL1 is a potential therapeutic agent for hormone
      resistant prostate cancer. 

PMID- 25605248
TI  - Stromal-derived factor-1alpha/CXCL12-CXCR4 chemotactic pathway promotes
      perineural invasion in pancreatic cancer.
AB  - Perineural invasion (PNI) is considered as an alternative route for the
      metastatic spread of pancreatic cancer cells; however, the molecular changes
      leading to PNI are still poorly understood. In this study, we show that the
      CXCL12/CXCR4 axis plays a pivotal role in the neurotropism of pancreatic cancer
      cells to local peripheral nerves. Immunohistochemical staining results revealed
      that CXCR4 elevation correlated with PNI in 78 pancreatic cancer samples. Both in
      vitro and in vivo PNI models were applied to investigate the function of the
      CXCL12/CXCR4 signaling in PNI progression and pathogenesis. The results showed
      that the activation of the CXCL12/CXCR4 axis significantly increased pancreatic
      cancer cells invasion and promoted the outgrowth of the dorsal root ganglia.
      CXCL12 derived from the peripheral nerves stimulated the invasion and chemotactic
      migration of CXCR4-positive cancer cells in a paracrine manner, eventually
      leading to PNI. In vivo analyses revealed that the abrogation of the activated
      signaling inhibited tumor growth and invasion of the sciatic nerve toward the
      spinal cord. These data indicate that the CXCL12/CXCR4 axis may be a novel
      therapeutic target to prevent the perineural dissemination of pancreatic cancer. 

PMID- 25605247
TI  - Statin-induced depletion of geranylgeranyl pyrophosphate inhibits cell
      proliferation by a novel pathway of Skp2 degradation.
AB  - Statins, such as lovastatin, can induce a cell cycle arrest in the G1 phase. This
      robust antiproliferative activity remains intact in many cancer cells that are
      deficient in cell cycle checkpoints and leads to an increased expression of CDK
      inhibitor proteins p27Kip1 and p21Cip1. The molecular details of this statin
      induced growth arrest remains unclear. Here we present evidence that lovastatin
      can induce the degradation of Skp2, a subunit of the SCFSkp2 ubiquitin ligase
      that targets p27Kip1 and p21Cip1 for proteasomal destruction. The statin-induced
      degradation of Skp2 is cell cycle phase independent and does not require its well
      characterised degradation pathway mediated by APC/CCdh1- or Skp2
      autoubiquitination. An N-terminal domain preceding the F-box of Skp2 is both
      necessary and sufficient for its statin mediated degradation. The degradation of
      Skp2 results from statin induced depletion of geranylgeranyl isoprenoid
      intermediates of cholesterol biosynthesis. Inhibition of geranylgeranyl
      transferase-I also promotes APC/CCdh1- independent degradation of Skp2,
      indicating that de-modification of a geranylgeranylated protein triggers this
      novel pathway of Skp2 degradation. 

PMID- 25605249
TI  - Protein arginine methyltransferase 7 promotes breast cancer cell invasion through
      the induction of MMP9 expression.
AB  - Recent evidence points to the protein arginine methyltransferase (PRMT) family of
      enzymes playing critical roles in cancer. PRMT7 has been identified in several
      gene expression studies to be associated with increased metastasis and decreased
      survival in breast cancer patients. However, this has not been extensively
      studied. Here we report that PRMT7 expression is significantly upregulated in
      both primary breast tumour tissues and in breast cancer lymph node metastases. We
      have demonstrated that reducing PRMT7 levels in invasive breast cancer cells
      using RNA interference significantly decreased cell invasion in vitro and
      metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7
      cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the
      expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast
      cancer metastasis. Importantly, we significantly rescued invasion of aggressive
      breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our
      results demonstrate that upregulation of PRMT7 in breast cancer may have a
      significant role in promoting cell invasion through the regulation of MMP9. This
      identifies PRMT7 as a novel and potentially significant biomarker and therapeutic
      target for breast cancer. 

PMID- 25605251
TI  - KITENIN promotes glioma invasiveness and progression, associated with the
      induction of EMT and stemness markers.
AB  - KITENIN (KAI1 COOH-terminal interacting tetraspanin) promotes tumor invasion and
      metastasis in various cancers. This study assessed the association between
      KITENIN expression and advanced glioma grade in patients. In vitro assays
      revealed that KITENIN knockdown inhibited the invasion and migration of glioma
      cells, whereas KITENIN overexpression promoted their invasion and migration. In
      orthotopic mouse tumor models, mice transplanted with KITENIN-transfected glioma
      cells had significantly shorter survival than mice transplanted with mock
      transfected cells. Patients with low KITENIN expression showed a significantly
      longer progression-free survival than patients with high KITENIN expression.
      KITENIN induced the expression of the epithelial-mesenchymal transition (EMT)
      markers (N-cadherin, ZEB1, ZEB2, SNAIL and SLUG) as well as the glioma stemness
      markers (CD133, ALDH1 and EPH-B1). Taken together, these findings showed that
      high levels of KITENIN increased glioma invasiveness and progression, associated
      with the up-regulation of EMT and stemness markers. 

PMID- 25605250
TI  - Simultaneous targeting of androgen receptor (AR) and MAPK-interacting kinases
      (MNKs) by novel retinamides inhibits growth of human prostate cancer cell lines.
AB  - Androgen receptor (AR) and MNK activated eIF4E signaling promotes the development
      and progression of prostate cancer (PCa). In this study, we report that our Novel
      Retinamides (NRs) target both AR signaling and eIF4E translation in androgen
      sensitive and castration resistant PCa cells via enhancing AR and MNK degradation
      through ubiquitin-proteasome pathway. Dual blockade of AR and MNK initiated eIF4E
      activation by NRs in turn induced cell cycle arrest, apoptosis, and inhibited
      cell proliferation. NRs also inhibited cell migration and invasion in metastatic
      cells. Importantly, the inhibitory effects of NRs on AR signaling, eIF4E
      translation initiation and subsequent oncogenic program were more potent than
      that observed with clinically relevant retinoids, established MNK inhibitors, and
      the FDA approved PCa drugs. Our findings provide the first preclinical evidence
      that simultaneous inhibition of AR and eIF4E activation is a novel and
      efficacious therapeutic approach for PCa, and that NRs hold significant promise
      for treatment of advanced prostate cancer. 

PMID- 25605253
TI  - Selective inhibition of histone deacetylase 2 induces p53-dependent survivin
      downregulation through MDM2 proteasomal degradation.
AB  - In the present study, we found that selective inhibition of histone deacetylase 2
      (HDAC2) with small inhibitory RNA (siRNA) induced survivin downregulation in a
      p53-dependent manner. Interestingly, suberoylanilide hydroxamic acid (SAHA) or
      knockdown of HDAC2 induced downregulation of Mdm2, a negative regulator of p53,
      at the protein level. SAHA and/or HDAC2 siRNA increased Mdm2 ubiquitination, and
      MG132, an inhibitor of proteosome function, prevented HDAC2 inhibition-induced
      degradation of Mdm2. Clinically, the mRNA levels of HDAC2 and survivin were
      prominently overexpressed in lung cancer patients compared to normal lung
      tissues. Silencing of HDAC2 enhanced the cell death caused by ionizing radiation
      in lung cancer cells. Collectively, our results indicate that selective
      inhibition of HDAC2 causes survivin downregulation through activation of p53,
      which is mediated by downregulation of Mdm2. They further suggest that HDAC2 may
      exert a dominant effect on lung cancer cell survival by sustaining Mdm2-survivin
      levels. 

PMID- 25605252
TI  - Functional consequence of the MET-T1010I polymorphism in breast cancer.
AB  - Major breast cancer predisposition genes, only account for approximately 30% of
      high-risk breast cancer families and only explain 15% of breast cancer familial
      relative risk. The HGF growth factor receptor MET is potentially functionally
      altered due to an uncommon germline single nucleotide polymorphism (SNP), MET
      T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP
      is present in 2% of patients with metastatic breast cancer. Expression of MET
      T1010I in the context of mammary epithelium increases colony formation, cell
      migration and invasion in-vitro and tumor growth and invasion in-vivo. A
      selective effect of MET-T1010I as compared to wild type MET on cell invasion both
      in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor
      pathophysiology and should be considered as a potential biomarker when
      implementing MET targeted clinical trials. 

PMID- 25605254
TI  - Frequencies of SF3B1, NOTCH1, MYD88, BIRC3 and IGHV mutations and TP53
      disruptions in Chinese with chronic lymphocytic leukemia: disparities with
      Europeans.
AB  - We studied 307 consecutive Chinese with chronic lymphocytic leukemia (CLL) in
      diverse disease-stages before and after diverse therapies for mutations in
      several CLL-related genes. Mutation frequencies were SF3B1, 5%, NOTCH1, 8%,
      MYD88, 8%, BIRC3, 2%, TP53, 15% and IGHV, 60%. Several of these frequencies
      differ from those reported in persons of predominately European descent with CLL.
      Biological and clinical associations were detected including SF3B1 and NOTCH1
      mutations with un-mutated IGHV, MYD88 mutations with mutated IGHV, SF3B1
      mutations with fludarabine-resistant CLL and NOTCH1 mutation with advanced Binet
      disease stage and with +12. The NOTCH1 correlation with briefer survival was
      confirmed in multivariate analyses but the SF3B1 correlation was confounded by
      concurrent mutations in TP53 and germline IGHV. We show differences in incidence
      and prognostic impact of mutations in Chinese and CLL compared with persons of
      predominately European descent with CLL. These data may give insights into the
      etiology and biology of CLL and suggests different risk stratification models may
      be needed for different CLL populations. 

PMID- 25605255
TI  - A three-protein signature and clinical outcome in esophageal squamous cell
      carcinoma.
AB  - Current staging is inadequate to precisely predict clinical outcome of esophageal
      squamous cell carcinoma (ESCC) and determine treatment choices, which vary from
      operation alone to intensive multimodal regimens. The purpose of this study is to
      investigate the prognostic values of an immunohistochemistry-based three-protein
      signature model in patients with ESCC. We determined the protein expression of
      Annexin II, cofilin 1, ezrin, fascin, kindlin-2, moesin, MTSS1, myosin-9,
      profilin-1, Rac1, radixin, ROCK2, talin, tensin and villin 1 in a test cohort
      including 110 formalin-fixed, paraffin-embedded esophageal curative resection
      specimens by tissue microarrays (TMAs). A three-protein signature elicited from
      the protein cluster, Annexin II, kindlin-2, and myosin-9, was validated by TMAs
      on an independent cohort of 147 specimens. The expression of three-protein
      signature was highly predictive of ESCC overall survival (OS) and disease-free
      survival (DFS) in both generation and validation datasets. Regression analysis
      shows that this three-protein signature is an independent predictor for OS and
      DFS. Furthermore, the predictive ability of these 3 biomarkers in combination is
      more robust than that of each individual biomarker. This study demonstrates a
      clinically applicable prognostic model that accurately predicts ESCC patient
      survival and/or tumor recurrence, and thus could serve as a complement to current
      risk stratification approaches. 

PMID- 25605256
TI  - ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and
      serves as a prognostic marker for laryngeal cancer.
AB  - Although targeting radioresistant tumor cells is essential for enhancing the
      efficacy of radiotherapy, the signals activated in resistant tumors are still
      unclear. This study shows that ERp57 contributes to radioresistance of laryngeal
      cancer by activating STAT3. Increased ERp57 was associated with the
      radioresistant phenotype of laryngeal cancer cells. Interestingly, increased
      interaction between ERp57 and STAT3 was observed in radioresistant cells,
      compared to the control cells. This physical complex is required for the
      activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes,
      Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a
      chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant
      cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates
      radioresistance of laryngeal cancer cells. Furthermore, we observed a positive
      correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo
      interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we
      also found that increased ERp57-STAT3 complex was associated with poor prognosis
      in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3
      regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in
      radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might
      be important for enhancing the efficacy of radiotherapy in human laryngeal
      cancer. 

PMID- 25605257
TI  - Particle shedding from peristaltic pump tubing in biopharmaceutical drug product
      manufacturing.
AB  - In a typical manufacturing setup for biopharmaceutical drug products, the fill
      and dosing pump is placed after the final sterile filtration unit in order to
      ensure adequate dispensing accuracy and avoid backpressure peaks. Given the
      sensitivity of protein molecules, peristaltic pumps are often preferred over
      piston pumps. However, particles may be shed from the silicone tubing employed.
      In this study, particle shedding and a potential turbidity increase during
      peristaltic pumping of water and buffer were investigated using three types of
      commercially available silicone tubing. In the recirculates, mainly particles of
      around 200 nm next to a very small fraction of particles in the lower micrometer
      range were found. Using 3D laser scanning microscopy, surface roughness of the
      inner tubing surface was found to be a determining factor for particle shedding
      from silicone tubing. As the propensity toward particle shedding varied between
      tubing types and also cannot be concluded from manufacturer's specifications,
      individual testing with the presented methods is recommended during tubing
      qualification. Choosing low abrasive tubing can help to further minimize the very
      low particle counts to be expected in pharmaceutical drug products.

PMID- 25605258
TI  - [Treatment management of sexual offenders].
AB  - In France, the Court can issue a medical treatment order only for criminally
      responsible persons. The nature of the treatment to be administered is at the
      discretion of the physician in charge of the sexual offender's care. Treatment
      management of sexual offenders relies essentially on psychotherapy, and
      preferentially cognitive behavioral therapy. For most severe sexual offenders,
      drug treatments, including hormonal treatment and selective serotonin reuptake
      inhibitors, are used to complement psychotherapy. This literature review aims at
      synthesizing practice changes in the treatment management of sexual offenders. 

PMID- 25605259
TI  - Three-dimensional porous stretchable and conductive polymer composites based on
      graphene networks grown by chemical vapour deposition and PEDOT:PSS coating.
AB  - We have manufactured a highly conductive and stretchable composite by backfilling
      the 3D graphene-PEDOT:PSS skeleton with poly(dimethylsiloxane) (PDMS). The
      electrical conductivity of our product can reach 24 S cm(-1) with only 1.5 wt%
      graphene and 1.5 wt% PEDOT:PSS loading, and its resistance increased only 35%
      when stretched to 80% strain. 

PMID- 25605260
TI  - Features of infratentorial-predominant posterior reversible encephalopathy
      syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic process that
      typically occurs in the setting of immune dysregulation. In contrast to the
      characteristic pattern involving parieto-occipital and posterior frontal regions,
      predominant involvement of the infratentorial brain occurs in a minority of PRES
      patients. We examined six patients with infratentorial predominant posterior
      reversible encephalopathy syndrome (IPPRES) relative to those with typical PRES
      in terms of clinical factors of toxicity and outcomes. We review the current
      understanding of PRES pathophysiology. An institutional database of PRES patients
      was created through an IRB-approved search of the electronic record from 2007 to
      2012. MR images were reviewed and classified by two neuro radiologists. Clinical
      data including laboratory data, blood pressure, and discharge outcome were
      collected through review of existing electronic medical records. Characteristics
      of the two groups were compared. Six cases among 80 PRES patients displayed an
      atypical distribution of signal abnormality predominantly involving the
      infratentorial brain. In IPPRES patients, signal abnormalities within the
      supratentorial brain, when present, showed a predominantly central distribution
      rather than the typical peripheral distribution. IPPRES patients showed higher
      rates of extreme hypertension, renal dysfunction, abnormal serum calcium, and
      abnormal serum magnesium relative to typical PRES patients. Outcomes were similar
      between the two groups. In our small series, IPPRES differs from typical PRES
      patients not only in the distribution of imaging abnormalities but also in rates
      of extreme hypertension and several laboratory indices. Despite these
      differences, clinical outcome in the IPPRES group was similar to that of typical
      PRES. 

PMID- 25605262
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: tranexamic acid in life-threatening haematuria.
AB  - A shortcut review was carried out to establish whether tranexamic acid improves
      outcomes for patients with life-threatening haematuria. Sixteen papers were found
      in Medline using the reported searches, of which four presented the best evidence
      to answer the clinical question. The author, date and country of publication,
      patient group studied, study type, relevant outcomes, results and study
      weaknesses of these best papers are tabulated. It is concluded that the evidence
      is limited, but there may be a role for tranexamic acid in life-threatening
      haematuria, particularly in patients with autosomal-dominant polycystic kidney
      disease. 

PMID- 25605264
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: Should bite guards be used with laryngeal mask airways in
      adults?
AB  - A shortcut review was carried out to establish whether bite blocks should be used
      when a laryngeal mask airway is used in the emergency department. Eighteen papers
      were found using the reported searches and a further eight were found by scanning
      the reference lists. Ten presented the best evidence to answer the clinical
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these best papers
      are tabulated. It is concluded that bite guards should be used when laryngeal
      mask airways are employed in the emergency department. 

PMID- 25605261
TI  - Therapeutic effect of Cryptotanshinone on collagen-induced arthritis in rats via
      inhibiting nuclear factor kappa B signaling pathway.
AB  - The discovery of new therapeutic drugs with the ability of preventing
      inflammation and joint destruction with less adverse effects is extremely urgent
      for rheumatoid arthritis (RA). Cryptotanshinone (CTS), an active component
      isolated from the root of Salvia miltiorrhiza Bunge, has been reported to have
      antibacterial and antitumor effects. However, its effects on RA have not been
      clearly elucidated. Here, we investigated the therapeutic effect of CTS on type
      II collagen-induced arthritis (CIA) in rats and explored the underlying
      mechanisms. Our results revealed that CTS treatment efficaciously ameliorated
      inflammation and joint destruction of rats with CIA. Both in vivo and in vitro
      studies showed that CTS suppressed the production of proinflammatory cytokines
      including interleukin 1beta, tumor necrosis factor alpha, and interleukin 17alpha
      production and downregulated the production and activity of matrix
      metalloproteinase 9. By receptor activator of nuclear factor kappa B (NF-kappaB)
      ligand-induced bone marrow macrophages, we observed that CTS could inhibit
      osteoclast differentiation, which is critic for joint destruction. Further
      studies on inflammatory signaling revealed that CTS could inhibit the degradation
      of inhibitor of NF-kappaB (IkappaB) alpha in vivo and in vitro, prevent the
      nuclear translocation of NF-kappaB p65 induced by lipopolysaccharide in a time-
      and dose-dependent manner. By electrophoretic mobility shift assay and luciferase
      reporter assay, we found that CTS distinctively inhibited the NF-kappaB DNA
      binding activity and NF-kappaB-dependent luciferase activity. These results
      indicate that the therapeutic effect of CTS on CIA is accomplished mainly through
      the inhibition of NF-kappaB signaling. Our findings provide the evidence to
      develop CTS as a potential therapeutic agent for patients with RA. 

PMID- 25605265
TI  - A Comprehensive Evaluation System for Military Hospitals' Response Capability to
      Bio-terrorism.
AB  - The objective of this study is to establish a comprehensive evaluation system for
      military hospitals' response capacity to bio-terrorism. Literature research and
      Delphi method were utilized to establish the comprehensive evaluation system for
      military hospitals' response capacity to bio-terrorism. Questionnaires were
      designed and used to survey the status quo of 134 military hospitals' response
      capability to bio-terrorism. Survey indicated that factor analysis method was
      suitable to for analyzing the comprehensive evaluation system for military
      hospitals' response capacity to bio-terrorism. The constructed evaluation system
      was consisted of five first-class and 16 second-class indexes. Among them,
      medical response factor was considered as the most important factor with weight
      coefficient of 0.660, followed in turn by the emergency management factor with
      weight coefficient of 0.109, emergency management consciousness factor with
      weight coefficient of 0.093, hardware support factor with weight coefficient of
      0.078, and improvement factor with weight coefficient of 0.059. The constructed
      comprehensive assessment model and system are scientific and practical. 

PMID- 25605266
TI  - Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in
      Mouse Renal Tumor Model.
AB  - Renal cell carcinoma (RCC) microenvironment plays critical roles in antitumor
      immune response. Resveratrol exhibits a direct antitumor effect in various tumor
      models. However, the immunomodulatory effect of resveratrol on RCC
      microenvironment is unknown. In this study, we found that administration of low
      dose of resveratrol inhibits Renca tumor growth and its inhibition effect depends
      on CD8(+) T cells. Moreover, the proportion of regulatory T cells is decreased,
      while the proportion of myeloid-derived suppressor cells does not alter after
      resveratrol treatment. More importantly, massive amount of activated CD8(+) T
      cells accumulates in tumor microenvironment in the resveratrol-treated group and
      shows increased cytotoxicity, as indicated by a higher expression of Fas ligand.
      We also found that resveratrol switches the expression of T-helper (Th) 2
      cytokines such as interleukin (IL)-6 and IL-10 to Th 1 cytokines with dominance
      of interferon (IFN)-gamma, which increases the expression of Fas in Renca cells.
      Furthermore, we found resveratrol down-regulates angiogenesis along with
      decreased level of vascular endothelial growth factor in tumor microenvironment.
      Our results strongly suggest that resveratrol might be used for RCC immunotherapy
      through modulating tumor microenvironment. 

PMID- 25605267
TI  - Effect of Propofol on the Expression of MMP-9 and Its Relevant Inflammatory
      Factors in Brain of Rat with Intracerebral Hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is bleeding in brain caused by the rupture of
      brain blood vessel, which may lead to patient unconsciousness or death. In this
      study, we measured the expression of matrix metalloproteinase-9 (MMP-9) and its
      relevant inflammatory factors in the brain of rat with ICH. The effect of
      propofol on the expression of MMP-9 and inflammatory factors was investigated. We
      found the water content in the brain of ICH rats was significantly higher when
      compared with normal brain. Expression of MMP-9 and inflammatory factors IL-1beta
      and TNF-alpha were up-regulated in ICH rats. Medium or high concentration of
      propofol can alleviate ICH in rats by inhibition of the inflammatory factor
      release and up-regulation of MMP-9 in brain. Our study suggests the inflammatory
      response after reduction of ICH through promotion of MMP-9 expression and neurite
      regeneration. 

PMID- 25605268
TI  - Characterization of the torafugu (Takifugu rubripes) immunoglobulin heavy chain
      gene locus.
AB  - In this study, we investigated the immunoglobulin heavy (IGH) gene locus of
      torafugu (Takifugu rubripes) from publicly available assembly sequences and
      presented an annotated locus map, including the IGHV genes, pseudogenes, and IGHC
      genes. Three new IGHV gene families (IGHV3-IGHV5) were discovered. We observed
      the interspersion of IGHV1 and IGHV2 family members and that they often
      intermingled with each other, while other family members were further
      interspersed. Conservation of the promoter and recombination signal sequences
      (RSS) was observed in a family-specific manner. In addition to known variable
      region genes present on chromosome 5 (current torafugu genome assembly), we found
      34 additional IGHV genes on scaffold 287 and three novel potentially functional
      IGHD genes on scaffold 483. In total, the variable region of the torafugu IGH
      locus consists of at least 48 IGHV genes, seven IGHD genes, and six IGHJ genes.
      IGHC genes have also been mapped in this study, with three genes encoding
      immunoglobulin classes: IgT, IgM, and IgD. We confirmed the expression of newly
      identified IGHV3 family sequences in the spleen and kidney of adult torafugu and
      found a favorable IGHV segment usage by IgM and IgT. Possible structural
      variation in the IGHdelta locus was observed based on the current torafugu
      assembly. The complete characterization of the torafugu IGH locus will facilitate
      detailed studies of large-scale mechanisms associated with the recombination of
      the variable region genes and will offer insights into the genetic basis of the
      potential diversity in the antibody response observed in torafugu. 

PMID- 25605270
TI  - A fluorescent bistable [2]rotaxane molecular switch on SiO2 nanoparticles.
AB  - A fluorescent bistable [2]rotaxane terminated with an alkyne functional group was
      constructed and immobilized onto the surface of SiO2 nanoparticles through click
      reaction. The shuttling motion of the macrocycle component between two different
      stations was driven by external acid-base stimuli both in solution and on SiO2
      nanoparticles, accompanied by visual fluorescence changes. 

PMID- 25605269
TI  - Resilience and psychosocial adjustment in digestive system cancer.
AB  - The study aims to investigate the contributions of resilience, affective
      reactions and post traumatic growth (PTG) to psychosocial adjustment and
      behavioral changes among digestive system cancer patients in Israel. A sample of
      200 participants, 57.5 % men (from the 46 to 70-year age range), 1-4 years
      following diagnosis, completed an inventory assessing demographic and medical
      information, resilience, current positive affect (PA) and negative affect (NA),
      PTG, psychosocial adjustment and retrospective report of behavioral changes
      following cancer treatment. Resilience, PA and NA, and PTG were related to
      adjustment and/or reported behavioral changes, and PA, NA and PTG mediated some
      of the effects of resilience on adjustment and/or reported behavioral changes.
      The data underline the importance of resilience, affect, and PTG in the
      adjustment of digestive system cancer patients. Future studies are needed to
      better understand the associations of resilience with psychosocial adjustment and
      behavioral changes. This knowledge may help improve cancer survivors' adjustment.

PMID- 25605271
TI  - The strategic role of competency based medical education in health care reform: a
      case report from a small scale, resource limited, Caribbean setting.
AB  - BACKGROUND: Curacao is a Dutch Caribbean island with a relatively high aging
      population, a high prevalence of chronic diseases and a health care system that
      is driven by cost-containment. In 2009 the development of a new value-based
      health care (VBHC) system was initiated on the island, and a key role was
      identified for the St. Elisabeth Hospital as a (model) platform for implementing
      this initiative. We therefore decided to investigate for the requirements needed
      to build a health care environment that is conducive for change and capable of
      facilitating the smooth migration of existent services into an effective and
      sustainable VBHC system. FINDINGS: Our findings revealed that our chosen approach
      was well accepted by the stakeholders. We discovered that in order to achieve a
      new value based health care system based on a reliable and well-organized system,
      the competencies of health care providers and the quality of the health care
      system needs to be assured. For this, extra focus needs to be given to improving
      service and manpower development both during and after formal training.
      CONCLUSIONS: In order to achieve a VBHC system in a resource-limited environment,
      the standard of physicians' competencies and of the health care system need to be
      guaranteed. The quality of the educational process needs to be maintained and
      safeguarded within an integrated health care delivery system that offers support
      to all care delivery and teaching institutions within the community. Finally,
      collaborative efforts with international medical institutions are recommended.

PMID- 25605272
TI  - Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and
      normal serum tryptase levels.
AB  - BACKGROUND: Systemic mastocytosis is a clonal mast cell (MC) disease that can
      lead to potentially fatal anaphylactic reactions caused by excessive MC mediator
      release. The prevalence of mastocytosis in patients with Hymenoptera venom
      allergy is high, and thus the disease should be suspected in patients with severe
      reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT)
      levels. OBJECTIVE: We sought to evaluate the presence of clonal MC disorders in
      patients seen at our mastocytosis center with Hymenoptera sting-induced
      anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal
      SBT levels. METHODS: Twenty-two patients with Hymenoptera sting-induced
      anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4
      ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in
      those patients with ascertained mastocytosis. RESULTS: In 16 of 22 patients, a
      diagnosis of indolent mastocytosis could be established, and 1 patient had a
      monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT
      levels (P = .03) but only rarely had angioedema/urticaria associated with
      hypotension (P = .004). CONCLUSIONS: The absence of urticaria or angioedema in
      severe reactions to Hymenoptera stings with hypotension might represent the most
      relevant factor in identifying patients with mastocytosis, regardless of their
      serum tryptase levels.

PMID- 25605273
TI  - Defective natural killer-cell cytotoxic activity in NFKB2-mutated CVID-like
      disease.

PMID- 25605275
TI  - Finally, the opportunity to publish systematic review protocols, systemic reviews
      and guidelines in animal health, animal welfare, and food safety.

PMID- 25605274
TI  - T-cell regulation during viral and nonviral asthma exacerbations.

PMID- 25605276
TI  - An introduction to systematic reviews in animal health, animal welfare, and food
      safety.
AB  - In this paper, we provide an introduction to systematic reviews and discuss the
      process for conducting systematic reviews in animal health, animal welfare, and
      food safety. The research synthesis need that can be addressed by a systematic
      review is discussed. The use of systematic reviews to address questions about
      intervention effects, etiology, diagnostic tests evaluation and disease burden
      are discussed. The steps included in a systematic review are described. 

PMID- 25605277
TI  - Pain management in the neonatal piglet during routine management procedures. Part
      1: a systematic review of randomized and non-randomized intervention studies.
AB  - Routine procedures carried out on piglets (i.e. castration, tail docking, teeth
      clipping, and ear notching) are considered painful. Unfortunately the efficacy of
      current pain mitigation modalities is poorly understood. The aim of this
      systematic review was to synthesize the existing primary scientific literature
      regarding the effectiveness of pain management interventions used for routine
      procedures on piglets. The review question was, 'In piglets under twenty-eight
      days old, undergoing castration, tail docking, teeth clipping, and/or methods of
      identification that involve cutting of the ear tissue, what is the effect of pain
      mitigation compared with no pain mitigation on behavioral and non-behavioral
      outcomes that indicate procedural pain and post-procedural pain?' A review
      protocol was designed a priori. Data sources used were Agricola (EBSCO), CAB
      Abstracts (Thomson Reuters), PubMed, Web of Science (Thomson Reuters), BIOSIS
      Previews (Thomson Reuters), and ProQuest Dissertations & Theses Full Text. No
      restrictions on year of publication or language were placed on the search.
      Eligible studies assessed an intervention designed to mitigate the pain of the
      procedures of interest and included a comparison group that did not receive an
      intervention. Eligible non-English studies were translated using a translation
      service. Two reviewers independently screened titles and abstracts for relevance
      using pre-defined questions. Data were extracted from relevant articles onto pre
      defined forms. From the 2203 retrieved citations forty publications, containing
      52 studies met the eligibility criteria. In 40 studies, piglets underwent
      castration only. In seven studies, piglets underwent tail docking only. In one
      study, piglets underwent teeth clipping only, and in one study piglets underwent
      ear notching only. Three studies used multiple procedures. Thirty-two trial arms
      assessed general anesthesia protocols, 30 trial arms assessed local anesthetic
      protocols, and 28 trial arms assessed non-steroidal anti-inflammatory drugs
      (NSAIDs) protocols. Forty-one trial arms were controls where piglets received
      either placebo or no treatment. Forty-five outcomes were extracted from the
      studies, however only the results from studies that assessed cortisol (six
      studies), beta-endorphins (one study), vocalisations (nine studies), and pain
      related behaviors (nine studies) are reported. Other outcomes were reported in
      only one or two studies. Confident decision making will likely be difficult based
      on this body of work because lack of comprehensive reporting precludes
      calculation of the magnitude of pain mitigation for most outcomes. 

PMID- 25605278
TI  - Pain management in the neonatal piglet during routine management procedures. Part
      2: grading the quality of evidence and the strength of recommendations.
AB  - Piglets reared in swine production in the USA undergo painful procedures that
      include castration, tail docking, teeth clipping, and identification with ear
      notching or tagging. These procedures are usually performed without pain
      mitigation. The objective of this project was to develop recommendations for pain
      mitigation in 1- to 28-day-old piglets undergoing these procedures. The National
      Pork Board funded project to develop recommendations for pain mitigation in
      piglets. Recommendation development followed a defined multi-step process that
      included an evidence summary and estimates of the efficacies of interventions.
      The results of a systematic review of the interventions were reported in a
      companion paper. This manuscript describes the recommendation development process
      and the final recommendations. Recommendations were developed for three
      interventions (CO2/O2 general anesthesia, non-steroidal anti-inflammatory drugs
      (NSAIDs), and lidocaine) for use during castration. The ability to make strong
      recommendations was limited by low-quality evidence and strong certainty about
      variation in stakeholder values and preferences. The panel strongly recommended
      against the use of a CO2/O2 general anesthesia mixture, weakly recommended for
      the use of NSAIDs and weakly recommended against the use of lidocaine for pain
      mitigation during castration of 1- to 28-day-old piglets. 

PMID- 25605279
TI  - Classical swine fever in pigs: recent developments and future perspectives.
AB  - Classical swine fever (CSF) is one of the most devastating epizootic diseases of
      pigs, causing high morbidity and mortality worldwide. The diversity of clinical
      signs and similarity in disease manifestations to other diseases make CSF
      difficult to diagnose with certainty. The disease is further complicated by the
      presence of a number of different strains belonging to three phylogenetic groups.
      Advanced diagnostic techniques allow detection of antigens or antibodies in
      clinical samples, leading to implementation of proper and effective control
      programs. Polymerase chain reaction (PCR)-based methods, including portable real
      time PCR, provide diagnosis in a few hours with precision and accuracy, even at
      the point of care. The disease is controlled by following a stamping out policy
      in countries where vaccination is not practiced, whereas immunization with live
      attenuated vaccines containing the 'C' strain is effectively used to control the
      disease in endemic countries. To overcome the problem of differentiation of
      infected from vaccinated animals, different types of marker vaccines, with
      variable degrees of efficacy, along with companion diagnostic assays have been
      developed and may be useful in controlling and even eradicating the disease in
      the foreseeable future. The present review aims to provide an overview and status
      of CSF as a whole with special reference to swine husbandry in India. 

PMID- 25605280
TI  - Death due to acute tetrachloroethylene intoxication in a chronic abuser.
AB  - Volatile substances are used widespread, especially among young people, as a
      cheap and easily accessible drug. Tetrachloroethylene is one of the solvents
      exerting effects on the central nervous system with experiences of disinhibition
      and euphoria. The case presented is that of a 27-year-old female, found dead by
      her father at home with cotton swabs dipped in the nostrils. She was already
      known for this type of abuse and previously admitted twice to the hospital for
      nonfatal acute poisonings. The swabs were still soaked in tetrachloroethylene.
      Toxicological and histological investigations demonstrated the presence of an
      overlap between chronic intake of the substance (with high concentrations in
      sites of accumulation, e.g., the adipose tissue, and contemporary tissue damage,
      as histologically highlighted) and acute intoxication as final cause of death,
      with a concentration of 158 mg/L in cardiac blood and 4915 mg/kg in the adipose
      tissue. No other drugs or medicines were detected in body fluids or tissues, and
      to our knowledge, this is the highest concentration ever detected in forensic
      cases. This peculiar case confirms the toxicity of this substance and focuses on
      the importance of complete histological and toxicological investigations in the
      distinction between chronic abuse and acute intoxication.

PMID- 25605281
TI  - Physicians' antibiotic prescribing behavior in Taiwan, 1998-2011.

PMID- 25605282
TI  - Outcomes of invasive meningococcal disease in adults and children in Canada
      between 2002 and 2011: a prospective cohort study.
AB  - BACKGROUND: Neisseria meningitidis causes 500 000 cases of septicemia and
      meningitis worldwide annually, with approximately 200 cases in Canada each year.
      Previous studies describe a case-fatality rate of 5%-15% and up to 20% of
      survivors suffering from long-term disability. METHODS: This study was performed
      in Canada between 2002 and 2011; the study area included >50% of the country's
      population. We identified risk factors associated with death and the development
      of complications in children and adults admitted to hospital with confirmed
      invasive meningococcal disease (IMD). Clinical information was obtained from
      hospital records. Risk factors for death and complications were analyzed by
      univariate and multivariable analyses. RESULTS: Of 868 individuals hospitalized
      with IMD, there were 73 deaths (8.4%) and 157 (18%) developed complications. The
      most common complications were hearing loss (5.4%), skin scarring (5.4%),
      amputation (3.4%), renal dysfunction (2.6%), and seizures (2.5%). Mortality was
      independently associated with shock (adjusted odds ratio [aOR], 23.30; P<.0001),
      age (aOR, 1.02 per 1-year increased age; P<.0001), symptom onset within 24 hours
      of admission (aOR, 1.80; P=.0471), and admission to the intensive care unit (aOR,
      0.41; P=.0196). Development of complications was independently associated with
      seizures (aOR, 4.55; P<.0001), shock (aOR, 3.10; P<.0001), abnormal platelet
      count (aOR, 2.14; P=.0002), bruising (aOR, 3.17; P=.0059), abnormal white blood
      cell count (aOR, 0.52; P=.0100), and prior antibiotic exposure (aOR, 0.27;
      P=.0273). CONCLUSIONS: Outcomes following IMD remain poor in this resource-rich
      setting in the 21st century. These data identify priorities for clinical
      management of adults and children with IMD, and provide prognostic information
      for affected patients and their families and cost-effectiveness analyses for
      meningococcal vaccine programs.

PMID- 25605283
TI  - Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective,
      multicenter, randomized controlled study in China.
AB  - BACKGROUND: Clofazimine (Cfz) has shown activity against Mycobacterium
      tuberculosis, including multidrug-resistant (MDR) strains in vitro and in animal
      studies. Here we evaluate the clinical efficacy and tolerability of using Cfz to
      treat MDR tuberculosis in China. METHODS: We enrolled 105 patients who had sputum
      culture-positive MDR tuberculosis in 6 major tuberculosis specialty hospitals in
      China. Patients were randomly assigned to either the Cfz therapy group (n = 53)
      or control group (n = 52). Patients in the 2 groups were given 21 months of
      individual-based chemotherapy regimens based on medication history and drug
      susceptibility test results. The Cfz therapy group regimens incorporated 100 mg
      of Cfz once daily for 21 months. RESULTS: Three patients in each group
      discontinued therapy because of side effects or other reasons. Sputum culture
      conversion to negative was earlier in patients who received Cfz compared with
      controls (P = .042 by log-rank test). Chest computed tomography showed cavitary
      changes in 46 patients in the Cfz therapy group and 45 in the control group.
      Cavity closure was earlier in patient who received Cfz compared with controls (P
      = .047 by log-rank test). The treatment success rate in the Cfz group was 73.6%,
      higher than that in control group (53.8%; P = .035). Side effects in skin only
      occurred in the Cfz group. The rates of skin discoloration and ichthyosis were
      94.3% and 47.2%, respectively. CONCLUSIONS: Using Cfz to treat MDR tuberculosis
      promotes cavity closure, accelerates sputum culture conversion, and improves
      treatment success rates.

PMID- 25605285
TI  - Importance of in situ preservation of parathyroid glands during total
      thyroidectomy.
AB  - BACKGROUND: Parathyroid failure is the most common complication after total
      thyroidectomy but factors involved are not completely understood. Accidental
      parathyroidectomy and parathyroid autotransplantation resulting in fewer than
      four parathyroid glands remaining in situ, and intensity of medical treatment of
      postoperative hypocalcaemia may have relevant roles. The aim of this study was to
      determine the relationship between the number of parathyroid glands remaining in
      situ and parathyroid failure after total thyroidectomy. METHODS: Consecutive
      patients undergoing first-time total thyroidectomy were studied prospectively,
      recording the number of Parathyroid Glands Remaining In Situ (PGRIS = 4 - (glands
      autografted + glands in the specimen)) and the occurrence of postoperative
      hypocalcaemia, and protracted and permanent hypoparathyroidism. Demographic,
      disease-related, laboratory and surgical variables were recorded. Patients were
      classified according to the PGRIS number into group 1-2 (one or two PGRIS), group
      3 (three PGRIS) and group 4 (all four glands remaining in situ), and were
      followed for at least 1 year. RESULTS: A total of 657 patients were included, 43
      in PGRIS group 1-2, 186 in group 3 and 428 in group 4. The prevalence of
      hypocalcaemia, and of protracted and permanent hypoparathyroidism was inversely
      related to the PGRIS score (group 1-2: 74, 44 and 16 per cent respectively; group
      3: 51.1, 24.7 and 6.5 per cent; group 4: 35.3, 13.1 and 2.6 per cent; P < 0.001).
      Intact parathyroid hormone concentrations at 24 h and 1 month were inversely
      correlated with PGRIS score (P < 0.001). Logistic regression identified PGRIS
      score as the most powerful variable influencing acute and chronic parathyroid
      failure. In addition, a normal-high serum calcium concentration 1 month after
      thyroidectomy influenced positively the recovery rate from protracted
      hypoparathyroidism in all PGRIS categories. CONCLUSION: In situ parathyroid
      preservation is critical in preventing permanent hypoparathyroidism after total
      thyroidectomy. Active medical treatment of postoperative hypocalcaemia has a
      positive synergistic effect.

PMID- 25605284
TI  - Phytohormone-mediated interkingdom signaling shapes the outcome of rice
      Xanthomonas oryzae pv. oryzae interactions.
AB  - BACKGROUND: Small-molecule hormones are well known to play key roles in the plant
      immune signaling network that is activated upon pathogen perception. In contrast,
      little is known about whether phytohormones also directly influence microbial
      virulence, similar to what has been reported in animal systems. RESULTS: In this
      paper, we tested the hypothesis that hormones fulfill dual roles in plant-microbe
      interactions by orchestrating host immune responses, on the one hand, and
      modulating microbial virulence traits, on the other. Employing the rice
      Xanthomonas oryzae pv. oryzae (Xoo) interaction as a model system, we show that
      Xoo uses the classic immune hormone salicylic acid (SA) as a trigger to activate
      its virulence-associated quorum sensing (QS) machinery. Despite repressing
      swimming motility, sodium salicylate (NaSA) induced production of the Diffusible
      Signal Factor (DSF) and Diffusible Factor (DF) QS signals, with resultant
      accumulation of xanthomonadin and extracellular polysaccharides. In contrast,
      abscisic acid (ABA), which favors infection by Xoo, had little impact on DF- and
      DSF-mediated QS, but promoted bacterial swimming via the LuxR solo protein OryR.
      Moreover, we found both DF and DSF to influence SA- and ABA-responsive gene
      expression in planta. CONCLUSIONS: Together our findings indicate that the rice
      SA and ABA signaling pathways cross-communicate with the Xoo DF and DSF QS
      systems and underscore the importance of bidirectional interkingdom signaling in
      molding plant-microbe interactions.

PMID- 25605286
TI  - TGF-beta converts Th1 cells into Th17 cells through stimulation of Runx1
      expression.
AB  - Differentiated CD4(+) T cells preserve plasticity under various conditions.
      However, the stability of Th1 cells is unclear, as is whether Th1 cells can
      convert into Th17 cells and thereby contribute to the generation of IFN-gamma(+)
      IL-17(+) CD4(+) T cells, the number of which correlates with severity of colitis.
      We investigated whether IFN-gamma(+) Th1 cells can convert into Th17 cells under
      intestinal inflammation and the mechanisms involved. IFN-gamma(Thy1.1+) Th1 cells
      were generated by culturing naive CD4(+) T cells from IFN-gamma(Thy1.1) CBir1 TCR
      Tg reporter mice, whose TCR is specific for an immunodominant microbiota antigen,
      CBir1 flagellin, under Th1 polarizing conditions. IFN-gamma(Thy1.1+) Th1 cells
      induced colitis in Rag(-/-) mice after adoptive transfer and converted into IL
      17(+) Th17, but not Foxp3(+) Treg cells in the inflamed intestines. TGF-beta and
      IL-6, but not IL-1beta and IL-23, regulated Th1 conversion into Th17 cells. TGF
      beta induction of transcriptional factor Runx1 is crucial for the conversion,
      since silencing Runx1 by siRNA inhibited Th1 conversion into Th17 cells.
      Furthermore, TGF-beta enhanced histone H3K9 acetylation but inhibited H3K9
      trimethylation of Runx1- and ROR-gammat-binding sites on il-17 or rorc gene in
      Th1 cells. We conclude that Th1 cells convert into Th17 cells under inflammatory
      conditions in intestines, which is possibly mediated by TGF-beta induction of
      Runx1. 

PMID- 25605288
TI  - Smoking normalizes cerebral blood flow and oxygen consumption after 12-hour
      abstention.
AB  - Acute nicotine administration stimulates [(14)C]deoxyglucose trapping in thalamus
      and other regions of rat brain, but acute effects of nicotine and smoking on
      energy metabolism have rarely been investigated in human brain by positron
      emission tomography (PET). We obtained quantitative PET measurements of cerebral
      blood flow (CBF) and metabolic rate of oxygen (CMRO2) in 12 smokers who had
      refrained from smoking overnight, and in a historical group of nonsmokers,
      testing the prediction that overnight abstinence results in widespread, coupled
      reductions of CBF and CMRO2. At the end of the abstention period, global grey
      matter CBF and CMRO2 were both reduced by 17% relative to nonsmokers. At 15
      minutes after renewed smoking, global CBF had increased insignificantly, while
      global CMRO2 had increased by 11%. Regional analysis showed that CMRO2 had
      increased in the left putamen and thalamus, and in right posterior cortical
      regions at this time. At 60 and 105 minutes after smoking resumption, CBF had
      increased by 8% and CMRO2 had increased by 11-12%. Thus, we find substantial and
      global impairment of CBF/CMRO2 in abstaining smokers, and acute restoration by
      resumption of smoking. The reduced CBF and CMRO2 during acute abstention may
      mediate the cognitive changes described in chronic smokers.

PMID- 25605287
TI  - In vivo and ex vivo magnetic resonance spectroscopy of the infarct and the
      subventricular zone in experimental stroke.
AB  - Ex vivo high-resolution magic-angle spinning (HRMAS) provides metabolic
      information with higher sensitivity and spectral resolution than in vivo magnetic
      resonance spectroscopy (MRS). Therefore, we used both techniques to better
      characterize the metabolic pattern of the infarct and the neural progenitor cells
      (NPCs) in the ipsilateral subventricular zone (SVZi). Ischemic stroke rats were
      divided into three groups: G0 (non-stroke controls, n = 6), G1 (day 1 after
      stroke, n = 6), and G7 (days 6 to 8 after stroke, n = 12). All the rats underwent
      MRS. Three rats per group were analyzed by HRMAS. The remaining rats were used
      for immunohistochemical studies. In the infarct, both techniques detected
      significant metabolic changes. The most relevant change was in mobile lipids
      (2.80 ppm) in the G7 group (a 5.53- and a 3.95-fold increase by MRS and HRMAS,
      respectively). In the SVZi, MRS did not detect any significant metabolic change.
      However, HRMAS detected a 2.70-fold increase in lactate and a 0.68-fold decrease
      in N-acetylaspartate in the G1 group. None of the metabolites correlated with the
      1.37-fold increase in NPCs detected by immunohistochemistry in the G7 group. In
      conclusion, HRMAS improves the metabolic characterization of the brain in
      experimental ischemic stroke. However, none of the metabolites qualifies as a
      surrogate biomarker of NPCs.

PMID- 25605289
TI  - Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates
      postischemic damage.
AB  - The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains
      controversial. Here, we analyzed their contribution to postanoxic depolarization
      after ischemia in cultured neurons and in brain slices. We observed that
      pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the
      onset of postanoxic currents and reduced their slope, and that simultaneous
      inhibition did not further enhance the effects of blocking either one. These
      results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout
      mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal
      death that was reduced with P2X7 and pannexin-1 blockers as well as in
      organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently,
      we used transient middle cerebral artery occlusion to monitor the neuroprotective
      effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and
      their ablation in knockout mice, substantially attenuated the motor symptoms and
      reduced the infarct volume to ~50% of that in vehicle-treated or wild-type
      animals. These results show that P2X7 receptors and pannexin-1 channels are major
      mediators of postanoxic depolarization in neurons and of brain damage after
      ischemia, and that they operate in the same deleterious signaling cascade leading
      to neuronal and tissue demise. 

PMID- 25605291
TI  - How long is too long for cerebral cooling after ischemia in fetal sheep?
AB  - Therapeutic hypothermia can partially reduce long-term death and disability in
      neonates after hypoxic-ischemic encephalopathy. The aim of this study was to
      determine whether prolonging the duration of cooling from 3 days to 5 days could
      further improve outcomes of cerebral ischemia in near-term fetal sheep. Fetal
      sheep (0.85 gestation) received 30 minutes bilateral carotid artery occlusion
      followed by 3 days of normothermia (n = 8), 3 days of hypothermia (n = 8), or 5
      days of hypothermia (n=8) started 3 hours after ischemia. Sham controls received
      sham ischemia followed by normothermia (n = 8). Cerebral ischemia was associated
      with profound loss of electroencephalography power and spectral edge, with
      greater and more rapid recovery in both hypothermia groups (P<0.05). Ischemia was
      associated with severe loss of neurons in the cortex, hippocampus and thalamus (P
      < 0.05), with a significant improvement in both hypothermia groups. However, the
      ischemia-3-day hypothermia group showed greater neuronal survival in the cortex
      and dentate gyrus compared with ischemia-5-day hypothermia (P < 0.05). Ischemia
      was associated with induction of iba1-positive microglia, which was attenuated in
      both hypothermia groups (P < 0.05). Extending the duration of delayed therapeutic
      hypothermia from 3 to 5 days did not improve outcomes after severe ischemia, and
      was associated with reduced neuronal survival in some regions.

PMID- 25605290
TI  - A novel trigger for cholesterol-dependent smooth muscle contraction mediated by
      the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a
      mechanistic role for lipid rafts.
AB  - Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are
      cholesterol-enriched membrane microdomains that influence signal transduction. We
      previously showed that Rho-kinase-mediated Ca(2+) sensitization of vascular
      smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal
      role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase
      mediated VSM contraction in vivo and to link this effect to cholesterol and
      rafts. The SPC-induced VSM contraction measured using a cranial window model was
      reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The
      extent of SPC-induced contraction correlated with serum total cholesterol. Total
      cholesterol levels in the internal carotid artery (ICA) were significantly higher
      in rats fed a cholesterol diet compared with a control diet or a beta
      cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time
      PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the
      ICA in rats fed a cholesterol diet, but not in rats fed the beta-cyclodextrin
      diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an
      increase in cholesterol by beta-cyclodextrin inhibited SPC-induced contraction in
      a cranial window model. These results indicate that cholesterol potentiates SPC
      Rho-kinase-mediated contractions of importance in cerebral vasospasm and are
      compatible with a role for rafts in this process. 

PMID- 25605292
TI  - Aging impairs myogenic adaptation to pulsatile pressure in mouse cerebral
      arteries.
AB  - Stability of myogenic tone in middle cerebral arteries (MCA) is essential for
      adequate control over penetration of pressure waves into the distal portion of
      the cerebral microcirculation. Because the increased pulse pressure observed in
      advanced aging is associated with cerebromicrovascular injury, the effect of
      aging on myogenic response of mouse MCAs was determined. Aging did not affect the
      myogenic constriction in response to static increases in pressure, whereas it
      significantly impaired pulsatile pressure-induced myogenic tone. Impaired
      myogenic adaptation of MCAs to pulsatile pressure may allow high pressure to
      penetrate the distal portion of the cerebral microcirculation, contributing to
      microvascular damage. 

PMID- 25605293
TI  - The spectrum of MR detectable cortical microinfarcts: a classification study with
      7-tesla postmortem MRI and histopathology.
AB  - Cerebral microinfarcts (CMIs) are common neuropathologic findings in aging and
      dementia. We explored the spectrum of cortical CMIs that can be visualized with 7
      T magnetic resonance imaging (MRI). Thirty-three coronal brain slices of 11
      individuals with neuropathologically confirmed dementia were subjected to a high
      resolution postmortem 7 T MRI protocol. First, we identified all visible small (?
      5 mm) intracortical and juxtacortical lesions on postmortem MRI. Lesions were
      classified as CMI or nonCMI based on histology, and their MR features were
      recorded. Thirty lesions were identified on the initial MRI evaluation, of which
      twenty-three could be matched with histology. Histopathology classified 12
      lesions as CMIs, all of which were located intracortically. On the basis of their
      MR features, they could be classified as chronic gliotic CMIs--with or without
      cavitation or hemorrhagic components--and acute CMIs. Eleven MRI identified
      lesions were not of ischemic nature and most commonly enlarged or atypically
      shaped perivascular spaces. Their MRI features were similar to gliotic CMIs with
      or without cavitation, but these 'CMI mimics' were always located
      juxtacortically. 7 T postmortem MRI distinguishes different histopathologic types
      of cortical CMIs, with distinctive MR characteristics. On the basis of our
      findings, we propose in vivo rating criteria for the detection of intracortical
      CMIs.

PMID- 25605295
TI  - Composition of the essential oil of Stachys benthamiana Boiss. from the south of
      Iran.
AB  - The chemical composition of the essential oil (EO) obtained from the aerial parts
      of Stachys benthamiana Boiss. was analysed by using GC and GC/MS. Thirty-three
      components were identified in the oil. beta-Bisabolene (19.2%), humulene epoxide
      II (10.7%), epi-alpha-bisabolol (7.2%), (E)-gamma-bisabolene (6.9%), n-decanal
      (6.8%) and caryophyllene oxide (6.6%), were the main compounds in the EOs. This
      is the first report on the different chemical compositions of S. benthamiana EOs
      from the south of Iran. 

PMID- 25605294
TI  - Assessment of metabolic fluxes in the mouse brain in vivo using 1H-[13C] NMR
      spectroscopy at 14.1 Tesla.
AB  - (13)C magnetic resonance spectroscopy (MRS) combined with the administration of
      (13)C labeled substrates uniquely allows to measure metabolic fluxes in vivo in
      the brain of humans and rats. The extension to mouse models may provide exclusive
      prospect for the investigation of models of human diseases. In the present study,
      the short-echo-time (TE) full-sensitivity (1)H-[(13)C] MRS sequence combined with
      high magnetic field (14.1 T) and infusion of [U-(13)C6] glucose was used to
      enhance the experimental sensitivity in vivo in the mouse brain and the (13)C
      turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate
      C2, lactate C3, alanine C3, gamma-aminobutyric acid C2, C3 and C4 were obtained.
      A one-compartment model was used to fit (13)C turnover curves and resulted in
      values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA
      (1.05 +/- 0.04 MUmol/g per minute), the exchange flux between 2-oxoglutarate and
      glutamate Vx (0.48 +/- 0.02 MUmol/g per minute), the glutamate-glutamine exchange
      rate V(gln) (0.20 +/- 0.02 MUmol/g per minute), the pyruvate dilution factor
      K(dil) (0.82 +/- 0.01), and the ratio for the lactate conversion rate and the
      alanine conversion rate V(Lac)/V(Ala) (10 +/- 2). This study opens the prospect
      of studying transgenic mouse models of brain pathologies.

PMID- 25605297
TI  - Automatic lung tumor segmentation with leaks removal in follow-up CT studies.
AB  - PURPOSE: In modern oncology, disease progression and response to treatment are
      routinely evaluated with a series of volumetric scans. The number of tumors and
      their volume (mass) over time provides a quantitative measure for the evaluation.
      Thus, many of the scans are follow-up scans. We present a new, fully automatic
      algorithm for lung tumors segmentation in follow-up CT studies that takes
      advantage of the baseline delineation. METHODS: The inputs are a baseline CT scan
      and a delineation of the tumors in it and a follow-up scan; the output is the
      tumor delineations in the follow-up CT scan; the output is the tumor delineations
      in the follow-up CT scan. The algorithm consists of four steps: (1) deformable
      registration of the baseline scan and tumor's delineations to the follow-up CT
      scan; (2) segmentation of these tumors in the follow-up CT scan with the baseline
      CT and the tumor's delineations as priors; (3) detection and correction of follow
      up tumors segmentation leaks based on the geometry of both the foreground and the
      background; and (4) tumor boundary regularization to account for the partial
      volume effects. RESULTS: Our experimental results on 80 pairs of CT scans from 40
      patients with ground-truth segmentations by a radiologist yield an average DICE
      overlap error of 14.5 % ([Formula: see text]), a significant improvement from the
      30 % ([Formula: see text]) result of stand-alone level-set segmentation.
      CONCLUSION: The key advantage of our method is that it automatically builds a
      patient-specific prior to the tumor. Using this prior in the segmentation
      process, we developed an algorithm that increases segmentation accuracy and
      robustness and reduces observer variability.

PMID- 25605296
TI  - Examination of autoantibody status and clinical features associated with cancer
      risk and cancer-associated scleroderma.
AB  - OBJECTIVE: We previously reported a contemporaneous onset of cancer and
      scleroderma in patients with anti-RNA polymerase III antibodies, and we
      identified a biologic link between cancer and scleroderma. This investigation was
      designed to further evaluate whether autoantibody status and other
      characteristics are associated with cancer and a clustering of cancer with
      scleroderma onset. METHODS: Logistic regression analysis was performed to assess
      the relationship of 2 outcomes, cancer (model 1) and a short (+/-2 years) cancer
      scleroderma interval (model 2), with autoantibody status and scleroderma
      covariates. RESULTS: Of 1,044 scleroderma patients, 168 (16.1%) had cancer. In
      the adjusted model 1, only older age at scleroderma onset (odds ratio 1.04 [95%
      confidence interval 1.02-1.05]) and white race (odds ratio 2.71 [95% confidence
      interval 1.22-6.04]) were significantly associated with an increased overall risk
      of cancer. In the adjusted model 2, only anti-RNA polymerase III positivity (odds
      ratio 5.08 [95% confidence interval 1.60-16.1]) and older age at scleroderma
      onset (odds ratio 1.04 [95% confidence interval 1.00-1.08]) were significantly
      associated with a short cancer-scleroderma interval. While anti-RNA polymerase
      III positivity was associated with a short cancer-scleroderma interval
      independent of age at scleroderma onset, the cancer-scleroderma interval
      shortened with older age at scleroderma onset in other antibody groups
      (Spearman's correlation P < 0.05), particularly among patients with anti
      topoisomerase I antibodies and patients who were negative for anticentromere,
      anti-topoisomerase I, and anti-RNA polymerase III antibodies. CONCLUSION:
      Increased age at scleroderma onset is strongly associated with cancer risk
      overall. While anti-RNA polymerase III status is an independent marker of
      coincident cancer and scleroderma at any age, a clustering of cancer with
      scleroderma is also seen in patients with anti-topoisomerase I and other
      autoantibody specificities who develop scleroderma at older ages.

PMID- 25605298
TI  - Computer-aided analysis of prostate multiparametric MR images: an unsupervised
      fusion-based approach.
AB  - OBJECTIVE: The aim of this study is to provide an automatic framework for
      computer-aided analysis of multiparametric magnetic resonance (mp-MR) images of
      prostate. METHOD: We introduce a novel method for the unsupervised analysis of
      the images. An evidential C-means classifier was adapted for use with a
      segmentation scheme to address multisource data and to manage conflicts and
      redundancy. RESULTS: Experiments were conducted using data from 15 patients. The
      evaluation protocol consisted in evaluating the method abilities to classify
      prostate tissues, showing the same behaviour on the mp-MR images, into
      homogeneous classes. As the actual diagnosis was available, thanks to the
      correlation with histopathological findings, the assessment focused on the
      ability to segment cancer foci. The method exhibited global sensitivity and
      specificity of 70 and 88 %, respectively. CONCLUSION: The preliminary results
      obtained by these initial experiments showed that the method can be applied in
      clinical routine practice to help making decision especially for practitioners
      with limited experience in prostate MRI analysis.

PMID- 25605299
TI  - In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma
      xenografts in mice: capabilities, limitations and a comparison with
      bioluminescence imaging.
AB  - Small animal imaging is of increasing relevance in biomedical research. Studies
      systematically assessing the diagnostic accuracy of contrast-enhanced in vivo
      micro-CT of orthotopic glioma xenografts in mice do not exist. NOD/SCID/gammac(-/
      ) mice (n = 27) underwent intracerebral implantation of 2.5 * 10(6) GFP
      Luciferase-transduced U87MG cells. Mice underwent bioluminescence imaging (BLI)
      to detect tumor growth and afterwards repeated contrast-enhanced (300 ul Iomeprol
      i.v.) micro-CT imaging (80 kV, 75 uAs, 360 degrees  rotation, 1,000 projections,
      33 s scan time, resolution 40 * 40 * 53 um, 0.5 Gy/scan). Presence of tumors,
      tumor diameter and tumor volume in micro-CT were rated by two independent
      readers. Results were compared with histological analyses. Six mice with tumors
      confirmed by micro-CT received fractionated irradiation (3 * 5 Gy every other
      day) using the micro-CT (5 mm pencil beam geometry). Repeated micro-CT scans were
      tolerated well. Tumor engraftment rate was 74 % (n = 20). In micro-CT, mean tumor
      volume was 30 +/- 33 mm(3), and the smallest detectable tumor measured 360 * 620
      um. The inter-rater agreement (n = 51 micro-CT scans) for the item tumor yes/no
      was excellent (Spearman-Rho = 0.862, p < 0.001). Sensitivity and specificity of
      micro-CT were 0.95 and 0.71, respectively (PPV = 0.91, NPV = 0.83). BLI on day 21
      after tumor implantation had a sensitivity and specificity of 0.90 and 1.0,
      respectively (PPV = 1.0, NPV = 0.5). Maximum tumor diameter and volume in micro
      CT and histology correlated excellently (tumor diameter: 0.929, p < 0.001; tumor
      volume: 0.969, p < 0.001, n = 17). Irradiated animals showed a large central
      tumor necrosis. Longitudinal contrast enhanced micro-CT imaging of brain tumor
      growth in live mice is feasible at high sensitivity levels and with excellent
      inter-rater agreement and allows visualization of radiation effects.

PMID- 25605300
TI  - Highly undersampled peripheral Time-of-Flight magnetic resonance angiography:
      optimized data acquisition and iterative image reconstruction.
AB  - OBJECT: The aim of this study was to investigate the acceleration of peripheral
      Time-of-Flight magnetic resonance angiography using Compressed Sensing and
      parallel magnetic resonance imaging (MRI) while preserving image quality and
      vascular contrast. MATERIALS AND METHODS: An analytical sampling pattern is
      proposed that combines aspects of parallel MRI and Compressed Sensing. It is used
      in combination with a dedicated Split Bregman algorithm. This approach is
      compared with current state-of-the-art patterns and reconstruction algorithms.
      RESULTS: The acquisition time was reduced from 30 to 2.5 min in a study using ten
      volunteer data sets, while showing improved sharpness, better contrast and higher
      accuracy compared to state-of-the-art techniques. CONCLUSION: This study showed
      the benefits of the proposed dedicated analytical sampling pattern and Split
      Bregman algorithm for optimizing the Compressed Sensing reconstruction of highly
      accelerated peripheral Time-of-Flight data.

PMID- 25605301
TI  - Sewage sludge composting in a two-stage system: carbon and nitrogen
      transformations and potential ecological risk assessment.
AB  - The study examined how aeration rate (AR) in bioreactor (1.0 and 0.5l/min kg dm)
      at low C/N ratio (ca. 15-16) affected kinetics of organic matter (OM) removal,
      i.e. rate constant of OM removal (k) and maximum degradation of OM (A) and
      nitrogen evolution during sewage sludge composting. Moreover, potential
      ecological risk (Er) based on metal (Cd, Cr, Cu, Hg, Ni, Pb, Zn) content was
      evaluated. The process involved a two-stage system (bioreactor and windrow). In
      the bioreactor, at higher AR, k and A equaled 0.34 d(-1) and 101.9 g/kg dm,
      respectively; at lower AR k was 0.38 d(-1), however A 1.4-fold lower.
      Interestingly, in the windrow, k was much higher (0.086 d(-1)) for the biomass
      subjected to a lower AR, compared to 0.026 d(-1) at higher AR. Moreover, although
      at lower AR, k in the windrow was 4.4-fold lower than in the bioreactor, A was
      1.15-fold higher. Total N content in mature compost was on the level 23.51-22.35
      g/kg dm and metal concentration showed low ecological risk (Er < 16).

PMID- 25605302
TI  - Cascading effects of climate extremes on vertebrate fauna through changes to low
      latitude tree flowering and fruiting phenology.
AB  - Forest vertebrate fauna provide critical services, such as pollination and seed
      dispersal, which underpin functional and resilient ecosystems. In turn, many of
      these fauna are dependent on the flowering phenology of the plant species of such
      ecosystems. The impact of changes in climate, including climate extremes, on the
      interaction between these fauna and flora has not been identified or elucidated,
      yet influences on flowering phenology are already evident. These changes are well
      documented in the mid to high latitudes. However, there is emerging evidence that
      the flowering phenology, nectar/pollen production, and fruit production of long
      lived trees in tropical and subtropical forests are also being impacted by
      changes in the frequency and severity of climate extremes. Here, we examine the
      implications of these changes for vertebrate fauna dependent on these resources.
      We review the literature to establish evidence for links between climate extremes
      and flowering phenology, elucidating the nature of relationships between
      different vertebrate taxa and flowering regimes. We combine this information with
      climate change projections to postulate about the likely impacts on nectar,
      pollen and fruit resource availability and the consequences for dependent
      vertebrate fauna. The most recent climate projections show that the frequency and
      intensity of climate extremes will increase during the 21st century. These
      changes are likely to significantly alter mass flowering and fruiting events in
      the tropics and subtropics, which are frequently cued by climate extremes, such
      as intensive rainfall events or rapid temperature shifts. We find that in these
      systems the abundance and duration of resource availability for vertebrate fauna
      is likely to fluctuate, and the time intervals between episodes of high resource
      availability to increase. The combined impact of these changes has the potential
      to result in cascading effects on ecosystems through changes in pollinator and
      seed dispersal ecology, and demands a focused research effort. 

PMID- 25605303
TI  - Diffusion of antibiotics through the PilQ secretin in Neisseria gonorrhoeae
      occurs through the immature, sodium dodecyl sulfate-labile form.
AB  - In strains of Neisseria gonorrhoeae harboring the mtr and penB determinants that
      decrease permeation of antibiotics into the periplasm, mutation or deletion of
      the PilQ secretin of type IV pili increases resistance to penicillin by ~3-fold,
      indicating a role for PilQ in antibiotic permeation. In this study, we examined
      spontaneously arising mutants with decreased susceptibility to penicillin. One
      class of mutants had a phenotype indistinguishable from that of a previously
      characterized pilQ2 mutation that interfered with the formation of SDS-resistant
      PilQ multimers. A second class of mutants contained frameshift mutations in genes
      upstream of pilQ in the pilMNOPQ operon that increased resistance to levels
      similar to those of the pilQ2 mutation. In-frame deletions of these genes were
      constructed, but only the frameshift mutations increased antibiotic resistance,
      suggesting that the mutations had polar effects on PilQ. Consistent with this
      result, titration of wild-type PilQ levels revealed a direct correlation between
      resistance and expression levels of PilQ. To determine which form of PilQ, the
      monomer or the multimer, was responsible for antibiotic permeation, we
      manipulated and quantified these forms in different mutants. Deletion of PilW,
      which is responsible for the maturation of PilQ into SDS-resistant multimers, had
      no effect on resistance. Moreover, Western blot analysis revealed that while SDS
      resistant multimer levels were decreased by 26% in frameshift mutants, the levels
      of PilQ monomers were decreased by 48%. These data suggest that immature, SDS
      labile complexes, not mature, SDS-resistant PilQ complexes, serve as the route of
      entry of antibiotics into the periplasm. IMPORTANCE: The capacity of antibiotics
      to reach their target is crucial for their activity. In Neisseria gonorrhoeae,
      the PilQ secretin of type IV pili plays an important role in antibiotic influx
      when diffusion of antibiotics through porins is limited (e.g., in most resistant
      strains). On Western blots, PilQ exists both as a mature higher-order multimer
      and an immature, SDS-labile monomer. In this study, we examined spontaneously
      arising mutations in PilQ and in the genes upstream of PilQ in the pilMNOPQ
      operon that increase resistance to penicillin. We provide evidence that PilQ
      monomers associate by mass action to form immature multimers and that these
      complexes likely mediate the diffusion of antibiotics across the outer membrane.

PMID- 25605304
TI  - Many means to a common end: the intricacies of (p)ppGpp metabolism and its
      control of bacterial homeostasis.
AB  - In nearly all bacterial species examined so far, amino acid starvation triggers
      the rapid accumulation of the nucleotide second messenger (p)ppGpp, the effector
      of the stringent response. While for years the enzymes involved in (p)ppGpp
      metabolism and the significance of (p)ppGpp accumulation to stress survival were
      considered well defined, a recent surge of interest in the field has uncovered an
      unanticipated level of diversity in how bacteria metabolize and utilize (p)ppGpp
      to rapidly synchronize a variety of biological processes important for growth and
      stress survival. In addition to the classic activation of the stringent response,
      it has become evident that (p)ppGpp exerts differential effects on cell
      physiology in an incremental manner rather than simply acting as a biphasic
      switch that controls growth or stasis. Of particular interest is the intimate
      relationship of (p)ppGpp with persister cell formation and virulence, which has
      spurred the pursuit of (p)ppGpp inhibitors as a means to control recalcitrant
      infections. Here, we present an overview of the enzymes responsible for (p)ppGpp
      metabolism, elaborate on the intricacies that link basal production of (p)ppGpp
      to bacterial homeostasis, and discuss the implications of targeting (p)ppGpp
      synthesis as a means to disrupt long-term bacterial survival strategies. 

PMID- 25605305
TI  - Engineering the genome of Thermus thermophilus using a counterselectable marker.
AB  - Thermus thermophilus is an extremely thermophilic bacterium that is widely used
      as a model thermophile, in large part due to its amenability to genetic
      manipulation. Here we describe a system for the introduction of genomic point
      mutations or deletions using a counterselectable marker consisting of a
      conditionally lethal mutant allele of pheS encoding the phenylalanyl-tRNA
      synthetase alpha-subunit. Mutant PheS with an A294G amino acid substitution
      renders cells sensitive to the phenylalanine analog p-chlorophenylalanine.
      Insertion of the mutant pheS allele via a linked kanamycin resistance gene into a
      chromosomal locus provides a gene replacement intermediate that can be removed by
      homologous recombination using p-chlorophenylalanine as a counterselective agent.
      This selection is suitable for the sequential introduction of multiple mutations
      to produce a final strain unmarked by an antibiotic resistance gene. We
      demonstrated the utility of this method by constructing strains bearing either a
      point mutation in or a precise deletion of the rrsB gene encoding 16S rRNA. We
      also used this selection to identify spontaneous, large-scale deletions in the
      pTT27 megaplasmid, apparently mediated by either of the T. thermophilus insertion
      elements ISTth7 and ISTth8. One such deletion removed 121 kb, including 118
      genes, or over half of pTT27, including multiple sugar hydrolase genes, and
      facilitated the development of a plasmid-encoded reporter system based on beta
      galactosidase. The ability to introduce mutations ranging from single base
      substitutions to large-scale deletions provides a potentially powerful tool for
      engineering the genome of T. thermophilus and possibly other thermophiles as
      well. IMPORTANCE: Thermus thermophilus is an extreme thermophile that has played
      an important part in the development of both biotechnology and basic biological
      research. Its suitability as a genetic model system is established by its natural
      competence for transformation, but the scarcity of genetic tools limits the kinds
      of manipulations that can currently be performed. We have developed a
      counterselectable marker that allows the introduction of unmarked deletions and
      point mutations into the T. thermophilus genome. We find that this marker can
      also be used to select large chromosomal deletions apparently resulting from
      aberrant transposition of endogenous insertion sequences. This system has the
      potential to advance the genetic manipulation of this important model organism.

PMID- 25605306
TI  - Structural insights into the multispecific recognition of dipeptides of deep-sea
      gram-negative bacterium Pseudoalteromonas sp. strain SM9913.
AB  - Peptide uptake is important for nutrition supply for marine bacteria. It is also
      an important step in marine nitrogen cycling. However, how marine bacteria absorb
      peptides is still not fully understood. DppA is the periplasmic dipeptide binding
      protein of dipeptide permease (Dpp; an important peptide transporter in bacteria)
      and exclusively controls the substrate specificity of Dpp. Here, the substrate
      binding specificity of deep-sea Pseudoalteromonas sp. strain SM9913 DppA (PsDppA)
      was analyzed for 25 different dipeptides with various properties by using
      isothermal titration calorimetry measurements. PsDppA showed binding affinities
      for 8 dipeptides. To explain the multispecific substrate recognition mechanism of
      PsDppA, we solved the crystal structures of unliganded PsDppA and of PsDppA in
      complex with 4 different types of dipeptides (Ala-Phe, Met-Leu, Gly-Glu, and Val
      Thr). PsDppA alternates between an "open" and a "closed" form during substrate
      binding. Structural analyses of the 4 PsDppA-substrate complexes combined with
      mutational assays indicate that PsDppA binds to different substrates through a
      precise mechanism: dipeptides are bound mainly by the interactions between their
      backbones and PsDppA, in particular by anchoring their N and C termini through
      ion-pair interactions; hydrophobic interactions are important in binding
      hydrophobic dipeptides; and Lys457 is necessary for the binding of dipeptides
      with a C-terminal glutamic acid or glutamine. Additionally, sequence alignment
      suggests that the substrate recognition mechanism of PsDppA may be common in Gram
      negative bacteria. All together, our results provide structural insights into the
      multispecific substrate recognition mechanism of marine Gram-negative bacterial
      DppA, which provides a better understanding of the mechanisms of marine bacterial
      peptide uptake. IMPORTANCE: Peptide uptake plays a significant role in nutrition
      supply for marine bacteria. It is also an important step in marine nitrogen
      cycling. However, how marine bacteria recognize and absorb peptides is still
      unclear. This study analyzed the substrate binding specificity of deep-sea
      Pseudoalteromonas sp. strain SM9913 DppA (PsDppA; the dipeptide-binding protein
      of dipeptide permease) and solved the crystal structures of unliganded PsDppA and
      PsDppA in complex with 4 different types of dipeptides. The multispecific
      recognition mechanism of PsDppA for dipeptides is explained based on structural
      and mutational analyses. We also find that the substrate-binding mechanism of
      PsDppA may be common in Gram-negative bacteria. This study sheds light on marine
      Gram-negative bacterial peptide uptake and marine nitrogen cycling.

PMID- 25605307
TI  - Biosynthesis and transport of the lantibiotic mutacin 1140 produced by
      Streptococcus mutans.
AB  - Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N
      terminal leader peptide that is cleaved to yield the active antibacterial
      peptide. Significant advancements in molecular tools that promote the study of
      lantibiotic biosynthesis can be used in Streptococcus mutans. Herein, we further
      our understanding of leader peptide sequence and core peptide structural
      requirements for the biosynthesis and transport of the lantibiotic mutacin 1140.
      Our study on mutacin 1140 biosynthesis shows a dedicated secondary cleavage site
      within the leader peptide and the dependency of transport on core peptide
      posttranslational modifications (PTMs). The secondary cleavage site on the leader
      peptide is found at the -9 position, and secondary cleavage occurs before the
      core peptide is transported out of the cell. The coordinated cleavage at the -9
      position was absent in a lanT deletion strain, suggesting that the core peptide
      interaction with the LanT transporter enables uniform cleavage at the -9
      position. Following transport, the LanP protease was found to be tolerant to a
      wide variety of amino acid substitutions at the primary leader peptide cleavage
      site, with the exception of arginine at the -1 position. Several leader and core
      peptide mutations produced core peptide variants that had intermediate stages of
      PTM enzyme modifications, supporting the concept that PTM enzyme modifications,
      secondary cleavage, and transport are occurring in a highly coordinated fashion.
      IMPORTANCE: Mutacin 1140 belongs to the class I lantibiotic family of ribosomally
      synthesized and posttranslationally modified peptides (RiPPs). The biosynthesis
      of mutacin 1140 is a highly efficient process which does not lead to a
      discernible level of production of partially modified core peptide variants. The
      products isolated from an extensive mutagenesis study on the leader and core
      peptides of mutacin 1140 show that the posttranslational modifications (PTMs) on
      the core peptide occur under a highly coordinated dynamic process. PTMs are
      dictated by the distance of the core peptide modifiable residues from PTM enzyme
      active sites. The formation of lanthionine rings aids in the formation of
      successive PTMs, as was observed in a peptide variant lacking a C-terminal
      decarboxylation.

PMID- 25605308
TI  - Allosteric regulation of Lactobacillus plantarum xylulose 5-phosphate/fructose 6
      phosphate phosphoketolase (Xfp).
AB  - Xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp), which catalyzes
      the conversion of xylulose 5-phosphate (X5P) or fructose 6-phosphate (F6P) to
      acetyl phosphate, plays a key role in carbohydrate metabolism in a number of
      bacteria. Recently, we demonstrated that the fungal Cryptococcus neoformans Xfp2
      exhibits both substrate cooperativity for all substrates (X5P, F6P, and Pi) and
      allosteric regulation in the forms of inhibition by phosphoenolpyruvate (PEP),
      oxaloacetic acid (OAA), and ATP and activation by AMP (K. Glenn, C. Ingram-Smith,
      and K. S. Smith. Eukaryot Cell 13: 657-663, 2014). Allosteric regulation has not
      been reported previously for the characterized bacterial Xfps. Here, we report
      the discovery of substrate cooperativity and allosteric regulation among
      bacterial Xfps, specifically the Lactobacillus plantarum Xfp. L. plantarum Xfp is
      an allosteric enzyme inhibited by PEP, OAA, and glyoxylate but unaffected by the
      presence of ATP or AMP. Glyoxylate is an additional inhibitor to those previously
      reported for C. neoformans Xfp2. As with C. neoformans Xfp2, PEP and OAA share
      the same or possess overlapping sites on L. plantarum Xfp. Glyoxylate, which had
      the lowest half-maximal inhibitory concentration of the three inhibitors, binds
      at a separate site. This study demonstrates that substrate cooperativity and
      allosteric regulation may be common properties among bacterial and eukaryotic Xfp
      enzymes, yet important differences exist between the enzymes in these two
      domains. IMPORTANCE: Xylulose 5-phosphate/fructose 6-phosphate phosphoketolase
      (Xfp) plays a key role in carbohydrate metabolism in a number of bacteria.
      Although we recently demonstrated that the fungal Cryptococcus Xfp is subject to
      substrate cooperativity and allosteric regulation, neither phenomenon has been
      reported for a bacterial Xfp. Here, we report that the Lactobacillus plantarum
      Xfp displays substrate cooperativity and is allosterically inhibited by
      phosphoenolpyruvate and oxaloacetate, as is the case for Cryptococcus Xfp. The
      bacterial enzyme is unaffected by the presence of AMP or ATP, which act as a
      potent activator and inhibitor of the fungal Xfp, respectively. Our results
      demonstrate that substrate cooperativity and allosteric regulation may be common
      properties among bacterial and eukaryotic Xfps, yet important differences exist
      between the enzymes in these two domains.

PMID- 25605309
TI  - Identification of a putative flavin adenine dinucleotide-binding monooxygenase as
      a regulator for Myxococcus xanthus development.
AB  - Gene clusters coding for the chaperone/usher (CU) pathway are widely distributed
      in many important environmental and pathogenic microbes; however, information
      about the regulatory machineries controlling CU gene expression during
      multicellular morphogenesis is missing. The Myxococcus xanthus Mcu system,
      encoded by the mcuABCD gene cluster, represents a prototype of the archaic CU
      family that functions in spore coat formation. Using genome-wide transposon
      mutagenesis, we identified MXAN2872 to be a potential regulator of the mcuABC
      operon and demonstrated the necessity of MXAN2872 for mcuABC expression and
      fruiting body morphogenesis in early development. In silico, biochemical, and
      genetic analyses suggest that MXAN2872 encodes a Baeyer-Villiger monooxygenase
      (BVMO) of flavoproteins, and the potential cofactor-binding site as well as the
      BVMO fingerprint sequence is important for the regulatory role of the MXAN2872
      protein. The expression profile of mcuA in strains with an MXAN2872 deletion and
      point mutation agrees well with the timing of cell aggregation of these mutants.
      Furthermore, McuA could not be detected either in a fruA-null mutant, where
      starvation-induced aggregation was completely blocked, or in the glycerol-induced
      spores, where sporulation was uncoupled from cell aggregation. In sum, the
      present work uncovers a positive role for MXAN2872, a metabolic enzyme-encoding
      gene, in controlling M. xanthus development. MXAN2872 functions by affecting the
      onset of cell aggregation, thereby leading to a secondary effect on the timing of
      mcuABC expression of this model organism. IMPORTANCE: Identification of the
      players that drive Myxococcus xanthus fruiting body formation is necessary for
      studying the mechanism of multicellular morphogenesis in this model organism.
      This study identifies MXAN2872, a gene encoding a putative flavin adenine
      dinucleotide-binding monooxygenase, to be a new interesting regulator regulating
      the timing of developmental aggregation. In addition, MXAN2872 seems to affect
      the expression of the chaperone/usher gene cluster mcu in a manner that is
      aggregation dependent. Thus, in organisms characterized by a developmental cycle,
      expression of the chaperone/usher pathway can be controlled by morphological
      checkpoints, demonstrating another layer of complexity in the regulation of this
      conserved protein secretion pathway.

PMID- 25605310
TI  - Evidence that TP_0144 of Treponema pallidum is a thiamine-binding protein.
AB  - Thiamine pyrophosphate (TPP), the biologically active form of thiamine (also
      known as vitamin B1), is an essential cofactor for several important enzymes
      involved in carbohydrate metabolism, and therefore, it is required for all living
      organisms. We recently found that a thiamine-binding protein (TDE_0143) is
      essential for the survival of Treponema denticola, an important bacterial
      pathogen that is associated with human periodontitis. In this report, we provide
      experimental evidence showing that TP_0144, a homolog of TDE_0143 from the
      syphilis spirochete Treponema pallidum, is a thiamine-binding protein that has
      biochemical features and functions that are similar to those of TDE_0143. First,
      structural modeling analysis reveal that both TDE_0143 and TP_0144 contain a
      conserved TPP-binding site and share similar structures to the thiamine-binding
      protein of Escherichia coli. Second, biochemical analysis shows that these two
      proteins bind to TPP with similar dissociation constant (Kd) values (TDE_0143, Kd
      of 36.50 nM; TP_0144, Kd of 32.62 nM). Finally, heterologous expression of
      TP_0144 in a DeltaTDE_0143 strain, a previously constructed TDE_0143 mutant of T.
      denticola, fully restores its growth and TPP uptake when exogenous thiamine is
      limited. Collectively, these results indicate that TP_0144 is a thiamine-binding
      protein that is indispensable for T. pallidum to acquire exogenous thiamine, a
      key nutrient for bacterial survival. In addition, the studies shown in this
      report further underscore the feasibility of using T. denticola as a platform to
      study the biology and pathogenicity of T. pallidum and probably other
      uncultivable treponemal species as well. 

PMID- 25605311
TI  - The kinetics of relapse in DEK-NUP214-positive acute myeloid leukemia patients.
AB  - Preemptive treatment of relapse of acute myeloid leukemia (AML) holds the promise
      to improve the prognosis of this currently highly lethal condition. Proposed
      treatment modalities applicable in preemptive cytoreduction (e.g., demethylating
      agents or standard chemotherapy) differ substantially in interval from
      administration to antileukemic effect. The t(6;9) balanced translocation,
      producing the DEK-NUP214 fusion protein, is seen in only 1% of patients with AML.
      We hypothesized that in these patients, who relapse with a very high frequency, a
      more detailed knowledge of leukemic relapse growth kinetics would improve the
      personalized decision-making regarding re-administration of chemotherapy. Based
      on standardized quantitative PCR data, we therefore delineated the relapse
      kinetics in a cohort of 27 relapsing DEK-NUP214-positive patients treated in four
      different European countries. The prerelapse leukemic burden increased with a
      median doubling time of 13 d (range: 5-51 d, median: 0.71 logs/month, range: 0.18
      1.91 logs/month), with FLT3-ITD-positive patients relapsing significantly faster
      than FLT3-ITD-negative ones (median: 0.9 vs. 0.6 logs/month, Wilcoxon rank sum
      test, P = 0.041). Peripheral blood and bone marrow were equally useful for
      minimal residual disease (MRD) detection, and thus, we found that with sampling
      intervals of 2 months, 94% of relapses would be detected with a median time from
      MRD detection to hematological relapse of 64 d. In conclusion, this data provide
      algorithms for handling the rare patients with DEK-NUP214-positive AML allowing
      for planning of both MRD follow-up and, upon molecular relapse, the timing of
      cytoreduction or possibly transplant procedures.

PMID- 25605312
TI  - X-ray diffraction in temporally and spatially resolved biomolecular science.
AB  - Time-resolved Laue protein crystallography at the European Synchrotron Radiation
      Facility (ESRF) opened up the field of sub-nanosecond protein crystal structure
      analyses. There are a limited number of such time-resolved studies in the
      literature. Why is this? The X-ray laser now gives us femtosecond (fs) duration
      pulses, typically 10 fs up to ~50 fs. Their use is attractive for the fastest
      time-resolved protein crystallography studies. It has been proposed that single
      molecules could even be studied with the advantage of being able to measure X-ray
      diffraction from a 'crystal lattice free' single molecule, with or without
      temporal resolved structural changes. This is altogether very challenging R&D. So
      as to assist this effort we have undertaken studies of metal clusters that bind
      to proteins, both 'fresh' and after repeated X-ray irradiation to assess their X
      ray-photo-dynamics, namely Ta6Br12, K2PtI6 and K2PtBr6 bound to a test protein,
      hen egg white lysozyme. These metal complexes have the major advantage of being
      very recognisable shapes (pseudo spherical or octahedral) and thereby offer a
      start to (probably very difficult) single molecule electron density map
      interpretations, both static and dynamic. A further approach is to investigate
      the X-ray laser beam diffraction strength of a well scattering nano-cluster; an
      example from nature being the iron containing ferritin. Electron crystallography
      and single particle electron microscopy imaging offers alternatives to X-ray
      structural studies; our structural studies of crustacyanin, a 320 kDa protein
      carotenoid complex, can be extended either by electron based techniques or with
      the X-ray laser representing a fascinating range of options. General outlook
      remarks concerning X-ray, electron and neutron macromolecular crystallography as
      well as 'NMR crystallography' conclude the article. 

PMID- 25605313
TI  - Haemodynamic and renal sympathetic responses to V1b vasopressin receptor
      activation within the paraventricular nucleus.
AB  - NEW FINDINGS: What is the central question of this study? Does antagonism of V1b
      receptors prevent the haemodynamic and renal sympathetic nerve responses that
      occur with application of exogenous vasopressin into the paraventricular nucleus
      (PVN) of conscious, chronically instrumented rats? What is the main finding and
      its importance? Microinjection of vasopressin into the PVN increased mean
      arterial pressure, heart rate and renal sympathetic nerve activity, all of which
      were inhibited by pre-injection of the PVN with the V1b antagonist, nelivaptan.
      The administered vasopressin did not enter the peripheral circulation or increase
      plasma vasopressin. Ganglionic blockade prevented each of the responses,
      consistent with mediation by enhanced sympathetic output rather than an increase
      in circulating vasopressin. Vasopressin (VP) participates in regulation of
      haemodynamics and volume. Besides more classical actions as a circulating
      hormone, VP may act via release from axons and dendrites within the CNS. The
      paraventricular nucleus (PVN) possesses vasopressinergic neurons and a dense
      complement of VP receptors, including the V1b receptor, which has been implicated
      in several types of stress responses. We tested the hypothesis that antagonism of
      V1b receptors will prevent VP-induced increases in mean arterial pressure (MAP),
      heart rate (HR) and renal sympathetic nerve activity (RSNA). Studies were
      performed in conscious male Sprague-Dawley rats chronically instrumented with
      vascular catheters, renal nerve electrodes and a cannula stereotaxically directed
      into the PVN. Unilateral microinjection of VP into the PVN significantly
      increased MAP, HR and RSNA, peaking at 10 min. Pre-injection of the PVN with the
      selective V1b receptor antagonist, nelivaptan, did not alter baseline values but
      blocked the responses to VP. Ganglionic blockade with chlorisondamine decreased
      MAP and HR and abolished their increase in response to subsequent PVN application
      of VP. Injection of VP into the PVN did not alter plasma VP levels.
      Paraventricular nucleus injection with radiolabelled VP resulted in negligible
      radiolabelled VP in peripheral blood. These findings support the concept that, in
      basal conditions, PVN V1b receptor activation (rather than VP release into the
      periphery) may be implicated in the increases in MAP, HR and RSNA due to
      increased sympathetic outflow. While the role of V1a and oxytocin receptors
      cannot be excluded, these data suggest that further studies of the role of V1b
      receptor activation by endogenous VP during stress to effect neuroexcitation are
      warranted.

PMID- 25605314
TI  - Exposure to acoustic stimuli promotes the development and differentiation of
      neural stem cells from the cochlear nuclei through the clusterin pathway.
AB  - Stem cell therapy has attracted widespread attention for a number of diseases.
      Recently, neural stem cells (NSCs) from the cochlear nuclei have been identified,
      indicating a potential direction for the treatment of sensorineural hearing loss.
      Acoustic stimuli play an important role in the development of the auditory
      system. In this study, we aimed to determine whether acoustic stimuli induce NSC
      development and differentiation through the upregulation of clusterin (CLU) in
      NSCs isolated from the cochlear nuclei. To further clarify the underlying
      mechanisms involved in the development and differentiation of NSCs exposed to
      acoustic stimuli, we successfully constructed animal models in which was CLU
      silenced by an intraperitoneal injection of shRNA targeting CLI. As expected, the
      NSCs from rats treated with LV-CLU shRNA exhibited a lower proliferation ratio
      when exposed to an augmented acoustic environment (AAE). Furthermore, the
      inhibition of cell apoptosis induced by exposure to AAE was abrogated after
      silencing the expression of the CLU gene. During the differentiation of acoustic
      stimuli-exposed stem cells into neurons, the number of astrocytes was
      significantly reduced, as evidenced by the expression of the cell markers,
      microtubule associated protein-2 (MAP-2) and glial fibrillary acidic protein
      (GFAP), which was markedly inhibited when the CLU gene was silenced. Our results
      indicate that acoustic stimuli may induce the development and differentiation of
      NSCs from the cochlear nucleus mainly through the CLU pathway. Our study suggests
      that CLU may be a novel target for the treatment of sensorineural hearing loss. 

PMID- 25605315
TI  - Insulin-like growth factor II-producing metastatic colon cancer with recurrent
      hypoglycemia.
AB  - A 45-year-old man was referred to our hospital and found to have a tubular
      adenocarcinoma of the descending colon with multiple liver metastases. During
      hospitalization, the patient suffered recurrent hypoglycemic attacks that
      required intravenous 50% glucose infusion. He was diagnosed with non-islet cell
      tumor hypoglycemia (NICTH) because the colon cancer tissue obtained by biopsy was
      strongly stained for insulin-like growth factor-II (IGF-II) by
      immunohistochemistry. He received chemotherapy with oxaliplatin, 5-FU and
      leucovorin (FOLFOX) plus bevacizumab (Bmab), and showed a partial response. As
      the metastatic lesions decreased in size, the hypoglycemic attacks gradually
      disappeared. Subsequently, he received outpatient chemotherapy and maintained a
      high quality of life for about 10 months. Western blot analysis of IGF-II in
      serum at the time of admission showed a high-molecular-weight form of IGF-II,
      which was considered to have caused hypoglycemia. This patient presents a very
      rare case of colorectal cancer associated with NICTH syndrome due to production
      of high-molecular-weight IGF-II by cancer cells. It is important to investigate
      IGF-II expression in cancer tissues for establishing the diagnosis of NICTH in
      cases with intractable hypoglycemia complicated by advanced cancer.

PMID- 25605316
TI  - Determining the role of polymer molecular weight for high-performance all-polymer
      solar cells: its effect on polymer aggregation and phase separation.
AB  - The molecular weight of a conjugated polymer is one of the key factors
      determining the electrical, morphological, and mechanical properties as well as
      its solubility in organic solvents and miscibility with other polymers. In this
      study, a series of semicrystalline poly[(2,5-bis(2-hexyldecyloxy)phenylene)-alt
      (5,6-difluoro-4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole)] (PPDT2FBT)
      polymers with different number-average molecular weights (M(n)'s) (PPDT2FBT(L),
      M(n) = 12 kg/mol; PPDT2FBT(M), M(n) = 24 kg/mol; PPDT2FBT(H), M(n) = 40 kg/mol)
      were synthesized, and their photovoltaic properties as electron donors for all
      polymer solar cells (all-PSCs) with poly[[N,N'-bis(2-octyldodecyl)-napthalene
      1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)] (P(NDI2OD-T2))
      acceptor were studied. The M(n) effect of PPDT2FBT on the structural,
      morphological, electrical, and photovoltaic properties was systematically
      investigated. In particular, tuning the M(n) induced dramatic effects on the
      aggregation behaviors of the polymers and their bulk heterojunction morphology of
      all-PSCs, which was thoroughly examined by grazing incident X-ray scattering,
      resonant soft X-ray scattering, and other microscopy measurements. High M(n)
      PPDT2FBT(H) promoted a strong "face-on" geometry in the blend film, suppressed
      the formation of an excessively large crystalline domain, and facilitated
      molecularly intermixed phases with P(NDI2OD-T2). Therefore, the optimized all
      PSCs based on PPDT2FBT(H)/P(NDI2OD-T2) showed substantially higher hole and
      electron mobilities than those of PPDT2FBT(L)/P(NDI2OD-T2), leading to a power
      conversion efficiency exceeding 5%, which is one of the highest values for all
      PSCs reported thus far.

PMID- 25605317
TI  - Sorafenib for the treatment of thyroid cancer: an updated review.
AB  - INTRODUCTION: Sorafenib (Nexavar) is an oral multi-kinase inhibitor targeting B
      type Raf kinase (BRAF) (both wild type and BRAF(V600E)), VEGFR1, VEGFR2, VEGFR3,
      PDGFRbeta and RET (also RET/PTC) influencing both differentiated thyroid cancer
      (DTC) cell proliferation and angiogenesis. AREAS COVERED: Encouraging results
      achieved in numerous Phase II trials were confirmed in a Phase III study
      conducted in radioiodine-refractory DTC. Sorafenib compared to placebo
      significantly prolongs progression-free survival, 10.8 versus 5.8 months,
      respectively. However, its administration resulted mainly in disease
      stabilization. No complete remission was obtained in any study. Beneficial
      effects were also demonstrated for medullary and anaplastic thyroid cancer;
      however further studies fulfilling evidence based medicine criteria are
      necessary. Its toxicity profile is convergent with other VEGFR inhibitors. The
      most common treatment-related side-effects involve skin toxicity (predominantly
      hand-foot skin reaction, different rashes and alopecia), gastrointestinal
      disturbances (diarrhea, abdominal pain), constitutional adverse reactions
      (anorexia, weight loss, fatigue) and hypertension. Although most adverse
      reactions are manageable, > 50% of patients required dose reduction. EXPERT
      OPINION: Sorafenib constitutes the first line treatment option in advanced,
      radioiodine-refractory DTC. However, there are still no data on its efficacy in
      patients progressed after another tyrosine kinase inhibitor. Other applications
      of the drug, such as use as adjuvant therapy to 131-I treatment, requires further
      studies.

PMID- 25605318
TI  - Impending paradoxical embolus.

PMID- 25605319
TI  - Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines
      for management and care transitions in the emergency department and hospital.
AB  - BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI), formally
      referred to as complicated skin and soft tissue infections, include infections
      with resistance to previously effective antimicrobials. Increasing dramatically
      in incidence, they have become a challenging medical problem associated with high
      direct and indirect costs to both the medical system and society. OBJECTIVES: To
      describe the burden of ABSSSI and to explore multidisciplinary approaches to its
      management and new treatments that can be initiated in the emergency department.
      DISCUSSION: We offer a best practice model aimed at providing risk-stratified and
      convenient care for ABSSSI at the lowest possible cost, while minimizing
      complications, readmissions, and inappropriate antibiotic use. In doing so, we
      focus on the care provided by emergency physicians and hospitalists and the
      transition of management between them for inpatient care, as well as the
      facilitation of observation or direct-to-outpatient care for suitable patients.
      CONCLUSIONS: A standard, consistent, and multidisciplinary approach to ABSSSI can
      streamline care, reduce admissions, support antimicrobial stewardship, and
      improve clinical and resource consumption outcomes.

PMID- 25605320
TI  - Dual carpometacarpal dislocation.

PMID- 25605321
TI  - Lingual thyroid.

PMID- 25605322
TI  - Right heart thrombus in transit diagnosed by bedside ultrasound.

PMID- 25605323
TI  - Three-dimensional motion analysis and its application in total knee arthroplasty:
      what we know, and what we should analyze.
AB  - INTRODUCTION: This paper will review three-dimensional (3D) motion analysis
      studies done in my laboratory to present an overview of what we have found.
      MATERIALS AND METHODS: We have looked at parameters such as roll-back, rotation,
      the pivot center of rotation etc. using a 2D-3D registration technique by
      evaluating knees before and after implantation of a total knee arthroplasty.
      CONCLUSION: This technique allows comparison of preoperative motion to that after
      total knee surgery. We have found the phenomenon of "reverse screw-home" to be a
      common motion pattern in osteoarthritis and it is often present after
      implantation of a total knee prosthesis.

PMID- 25605324
TI  - Amniotic Fluid Soluble Myeloid Differentiation-2 (sMD-2) as Regulator of Intra
      amniotic Inflammation in Infection-induced Preterm Birth.
AB  - PROBLEM: TLR4 mediates host responses to pathogens through a mechanism that
      involves protein myeloid differentiation-2 (MD-2) and its soluble form sMD-2. The
      role of sMD2 in intra-amniotic inflammation-induced preterm birth has not been
      previously explored. METHOD OF STUDY: Human amniotic fluid (AF) sMD-2 was studied
      by Western blotting in 152 AF samples of patients who had an amniocentesis to
      rule-out infection (yes infection, n = 50; no infection, n = 50) or women with
      normal pregnancy outcome (second trimester genetic karyotyping, n = 26; third
      trimester lung maturity testing, n = 26). Histological localization and mRNA
      expression of MD2 in fetal membranes were studied by immunohistochemistry and RT
      PCR. The ability of fetal membrane to release sMD-2 and inflammatory cytokines
      was studied in vitro. RESULTS: Human AF contains three sMD-2 proteoforms whose
      levels of expression were lower at term. Intra-amniotic infection upregulated sMD
      2. MD-2 mRNA and immunohistochemistry findings concurred. In vitro, LPS and
      monensin increased, while cycloheximide decreased sMD-2 production. Recombinant
      sMD-2 modulated TNF-alpha and IL-6 levels in a dose- and time-dependent fashion.
      CONCLUSION: sMD2 proteoforms are constitutively present in human AF. The
      intensity of the intra-amniotic inflammatory response to bacteria or perhaps to
      other TLR4 ligands may be facilitated through synthesis and release of sMD2 by
      the amniochorion.

PMID- 25605325
TI  - Intragenomic distribution of RTE retroelements suggests intrachromosomal
      movement.
AB  - Much is known about the abundance of transposable elements (TEs) in eukaryotic
      genomes, but much is still unknown on their behaviour within cells. We employ
      here a combination of cytological, molecular and genomic approaches providing
      information on the intragenomic distribution and behaviour of non-long terminal
      repeat (LTR) retrotransposon-like elements (RTE). We microdissected every
      chromosome in a single first meiotic metaphase cell of the grasshopper
      Eyprepocnemis plorans and polymerase chain reaction (PCR) amplified a fragment of
      the RTE reverse transcriptase gene with specific primers. PCR products were
      cloned and 139 clones were sequenced. Analysis of molecular variance (AMOVA)
      showed significant intragenomic structure for these elements, with 4.6 % of
      molecular variance being found between chromosomes. A maximum likelihood tree
      built with the RTE sequences revealed the frequent presence of two or more
      elements showing very high similarity and being located on the same chromosome,
      thus suggesting intrachromosome movement. The 454 pyrosequencing of genomic DNA
      gave strong support to the microdissection results and provided evidence for the
      existence of 5' truncated elements. Our results thus indicate a tendency of RTE
      elements to reinsert into the same chromosome from where they were transcribed,
      which could be achieved if retrotranscription and insertion takes place
      immediately after transcription. 

PMID- 25605326
TI  - Differential vital staining of normal fibroblasts and melanoma cells by an
      anionic conjugated polyelectrolyte.
AB  - Molecular probes for imaging of live cells are of great interest for studying
      biological and pathological processes. The anionic luminescent conjugated
      polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used
      for vital staining of cultured fibroblasts as well as transformed cells with
      results indicating differential staining due to cell phenotype. Herein, we
      investigated the behavior of PTAA in two normal and five transformed cells lines.
      PTAA fluorescence in normal cells appeared in a peripheral punctated pattern
      whereas the probe was more concentrated in a one-sided perinuclear localization
      in the five transformed cell lines. In fibroblasts, PTAA fluorescence was
      initially associated with fibronectin and after 24 h partially localized to
      lysosomes. The uptake and intracellular target in malignant melanoma cells was
      more ambiguous and the intracellular target of PTAA in melanoma cells is still
      elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and
      microscopic analysis as well as viability assays showed no signs of negative
      influence on growth. Stained cells maintained their proliferation rate for at
      least 12 generations. Although the probe itself was nontoxic, photoinduced
      cellular toxicity was observed in both cell lines upon irradiation directly after
      staining. However, no cytotoxicity was detected when the cells were irradiated 24
      h after staining, indicating that the photoinduced toxicity is dependent on the
      cellular location of the probe. Overall, these studies certified PTAA as a useful
      agent for vital staining of cells, and that PTAA can potentially be used to study
      cancer-related biological and pathological processes.

PMID- 25605327
TI  - Loss of osteoblast Runx3 produces severe congenital osteopenia.
AB  - Congenital osteopenia is a bone demineralization condition that is associated
      with elevated fracture risk in human infants. Here we show that Runx3, like
      Runx2, is expressed in precommitted embryonic osteoblasts and that Runx3
      deficient mice develop severe congenital osteopenia. Runx3-deficient osteoblast
      specific (Runx3(fl/fl)/Col1alpha1-cre), but not chondrocyte-specific
      (Runx3(fl/fl)/Col1alpha2-cre), mice are osteopenic. This demonstrates that an
      osteoblastic cell-autonomous function of Runx3 is required for proper
      osteogenesis. Bone histomorphometry revealed that decreased osteoblast numbers
      and reduced mineral deposition capacity in Runx3-deficient mice cause this bone
      formation deficiency. Neonatal bone and cultured primary osteoblast analyses
      revealed a Runx3-deficiency-associated decrease in the number of active
      osteoblasts resulting from diminished proliferation and not from enhanced
      osteoblast apoptosis. These findings are supported by Runx3-null culture
      transcriptome analyses showing significant decreases in the levels of
      osteoblastic markers and increases in the levels of Notch signaling components.
      Thus, while Runx2 is mandatory for the osteoblastic lineage commitment, Runx3 is
      nonredundantly required for the proliferation of these precommitted cells, to
      generate adequate numbers of active osteoblasts. Human RUNX3 resides on
      chromosome 1p36, a region that is associated with osteoporosis. Therefore, RUNX3
      might also be involved in human bone mineralization. 

PMID- 25605328
TI  - USP7 cooperates with SCML2 to regulate the activity of PRC1.
AB  - USP7 is a protein deubiquitinase with an essential role in development. Here, we
      provide evidence that USP7 regulates the activity of Polycomb repressive complex
      1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by
      the association of one of the PCGF homologues (PCGF1 to PCGF6) with the common
      catalytic subunit RING1B. First, we show that SCML2, a Polycomb group protein
      that associates with PRC1.2 (containing PCGF2/MEL18) and PRC1.4 (containing
      PCGF4/BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4,
      allowing for the stabilization of BMI1. Chromatin immunoprecipitation (ChIP)
      experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes.
      Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated
      histone H2A (H2Aub), the catalytic product of PRC1 and key for its repressive
      activity. USP7 regulates the posttranslational status of RING1B and BMI1, a
      specific component of PRC1.4. Thus, not only does USP7 stabilize PRC1 components,
      its catalytic activity is also necessary to maintain a functional PRC1, thereby
      ensuring appropriate levels of repressive H2Aub. 

PMID- 25605329
TI  - Nucleoporin 62-like protein activates canonical Wnt signaling through
      facilitating the nuclear import of beta-catenin in zebrafish.
AB  - Nucleoporin p62 (Nup62) localizes in the central channel of nuclear pore
      complexes (NPCs) and regulates nuclear pore permeability and nucleocytoplasmic
      transport. However, the developmental roles of Nup62 in vertebrates remain
      largely unclear. Zebrafish Nup62-like protein (Nup62l) is a homolog of mammalian
      Nup62. The nup62l gene is maternally expressed, but its transcripts are
      ubiquitously distributed during early embryogenesis and enriched in the head,
      pharynx, and intestine of developing embryos. Activation of the Wnt/beta-catenin
      pathway positively modulates nup62l transcription, while Bmp signaling acts
      downstream of Wnt/beta-catenin signaling to negatively regulate nup62l
      expression. Overexpression of nup62l dorsalized embryos and enhanced gastrula
      convergence and extension (CE) movements. In contrast, knockdown of Nup62l led to
      ventralized embryos, an impediment to CE movements, and defects in specification
      of midline organ progenitors. Mechanistically, Nup62l acts as an activator of
      Wnt/beta-catenin signaling through interaction with and facilitation of nuclear
      import of beta-catenin-1/2 in zebrafish. Thus, Nup62l regulates dorsoventral
      patterning, gastrula CE movements, and proper specification of midline organ
      precursors through mediating the nuclear import of beta-catenins in zebrafish. 

PMID- 25605330
TI  - p54nrb/NONO regulates cyclic AMP-dependent glucocorticoid production by
      modulating phosphodiesterase mRNA splicing and degradation.
AB  - Glucocorticoid production in the adrenal cortex is activated in response to an
      increase in cyclic AMP (cAMP) signaling. The nuclear protein p54(nrb)/NONO
      belongs to the Drosophila behavior/human splicing (DBHS) family and has been
      implicated in several nuclear processes, including transcription, splicing, and
      RNA export. We previously identified p54(nrb)/NONO as a component of a protein
      complex that regulates the transcription of CYP17A1, a gene required for
      glucocorticoid production. Based on the multiple mechanisms by which
      p54(nrb)/NONO has been shown to control gene expression and the ability of the
      protein to be recruited to the CYP17A1 promoter, we sought to further define the
      molecular mechanism by which p54(nrb)/NONO confers optimal cortisol production.
      We show here that silencing p54(nrb)/NONO expression in H295R human
      adrenocortical cells decreases the ability of the cells to increase intracellular
      cAMP production and subsequent cortisol biosynthesis in response to
      adrenocorticotropin hormone (ACTH) stimulation. Interestingly, the expression of
      multiple phosphodiesterase (PDE) isoforms, including PDE2A, PDE3A, PDE3B, PDE4A,
      PDE4D, and PDE11A, was induced in p54(nrb)/NONO knockdown cells. Investigation of
      the mechanism by which silencing of p54(nrb)/NONO led to increased expression of
      select PDE isoforms revealed that p54(nrb)/NONO regulates the splicing of a
      subset of PDE isoforms. Importantly, we also identify a role for p54(nrb)/NONO in
      regulating the stability of PDE transcripts by facilitating the interaction
      between the exoribonuclease XRN2 and select PDE transcripts. In summary, we
      report that p54(nrb)/NONO modulates cAMP-dependent signaling, and ultimately cAMP
      stimulated glucocorticoid biosynthesis by regulating the splicing and degradation
      of PDE transcripts. 

PMID- 25605331
TI  - C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 complex
      assembly and supercomplex stabilization.
AB  - Mammalian mitochondria may contain up to 1,500 different proteins, and many of
      them have neither been confidently identified nor characterized. In this study,
      we demonstrated that C11orf83, which was lacking experimental characterization,
      is a mitochondrial inner membrane protein facing the intermembrane space. This
      protein is specifically associated with the bc1 complex of the electron transport
      chain and involved in the early stages of its assembly by stabilizing the bc1
      core complex. C11orf83 displays some overlapping functions with Cbp4p, a yeast
      bc1 complex assembly factor. Therefore, we suggest that C11orf83, now called
      UQCC3, is the functional human equivalent of Cbp4p. In addition, C11orf83
      depletion in HeLa cells caused abnormal crista morphology, higher sensitivity to
      apoptosis, a decreased ATP level due to impaired respiration and subtle, but
      significant, changes in cardiolipin composition. We showed that C11orf83 binds to
      cardiolipin by its alpha-helices 2 and 3 and is involved in the stabilization of
      bc1 complex-containing supercomplexes, especially the III2/IV supercomplex. We
      also demonstrated that the OMA1 metalloprotease cleaves C11orf83 in response to
      mitochondrial depolarization, suggesting a role in the selection of cells with
      damaged mitochondria for their subsequent elimination by apoptosis, as previously
      described for OPA1. 

PMID- 25605332
TI  - Role of phosphoinositide 3-OH kinase p110beta in skeletal myogenesis.
AB  - Phosphoinositide 3-OH kinase (PI3K) regulates a number of developmental and
      physiologic processes in skeletal muscle; however, the contributions of
      individual PI3K p110 catalytic subunits to these processes are not well-defined.
      To address this question, we investigated the role of the 110-kDa PI3K catalytic
      subunit beta (p110beta) in myogenesis and metabolism. In C2C12 cells,
      pharmacological inhibition of p110beta delayed differentiation. We next generated
      mice with conditional deletion of p110beta in skeletal muscle (p110beta muscle
      knockout [p110beta-mKO] mice). While young p110beta-mKO mice possessed a lower
      quadriceps mass and exhibited less strength than control littermates, no
      differences in muscle mass or strength were observed between genotypes in old
      mice. However, old p110beta-mKO mice were less glucose tolerant than old control
      mice. Overexpression of p110beta accelerated differentiation in C2C12 cells and
      primary human myoblasts through an Akt-dependent mechanism, while expression of
      kinase-inactive p110beta had the opposite effect. p110beta overexpression was
      unable to promote myoblast differentiation under conditions of p110alpha
      inhibition, but expression of p110alpha was able to promote differentiation under
      conditions of p110beta inhibition. These findings reveal a role for p110beta
      during myogenesis and demonstrate that long-term reduction of skeletal muscle
      p110beta impairs whole-body glucose tolerance without affecting skeletal muscle
      size or strength in old mice. 

PMID- 25605333
TI  - The orphan nuclear receptor Nur77 is a determinant of myofiber size and muscle
      mass in mice.
AB  - We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an
      important role in the regulation of glucose homeostasis and oxidative metabolism
      in skeletal muscle. Here, we show using both gain- and loss-of-function models
      that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of
      Nur77 in skeletal muscle in mice led to increases in myofiber size. Conversely,
      mice with global or muscle-specific deficiency in Nur77 exhibited reduced muscle
      mass and myofiber size. In contrast to Nur77 deficiency, deletion of the highly
      related nuclear receptor NOR1 (Nr4a3) had minimal effect on muscle mass and
      myofiber size. We further show that Nur77 mediates its effects on muscle size by
      orchestrating transcriptional programs that favor muscle growth, including the
      induction of insulin-like growth factor 1 (IGF1), as well as concomitant
      downregulation of growth-inhibitory genes, including myostatin, Fbxo32 (MAFbx),
      and Trim63 (MuRF1). Nur77-mediated increase in IGF1 led to activation of the Akt
      mTOR-S6K cascade and the inhibition of FoxO3a activity. The dependence of Nur77
      on IGF1 was recapitulated in primary myoblasts, establishing this as a cell
      autonomous effect. Collectively, our findings identify Nur77 as a novel regulator
      of myofiber size and a potential transcriptional link between cellular metabolism
      and muscle growth. 

PMID- 25605334
TI  - Nuclear GIT2 is an ATM substrate and promotes DNA repair.
AB  - Insults to nuclear DNA induce multiple response pathways to mitigate the
      deleterious effects of damage and mediate effective DNA repair. G-protein-coupled
      receptor kinase-interacting protein 2 (GIT2) regulates receptor internalization,
      focal adhesion dynamics, cell migration, and responses to oxidative stress. Here
      we demonstrate that GIT2 coordinates the levels of proteins in the DNA damage
      response (DDR). Cellular sensitivity to irradiation-induced DNA damage was highly
      associated with GIT2 expression levels. GIT2 is phosphorylated by ATM kinase and
      forms complexes with multiple DDR-associated factors in response to DNA damage.
      The targeting of GIT2 to DNA double-strand breaks was rapid and, in part,
      dependent upon the presence of H2AX, ATM, and MRE11 but was independent of MDC1
      and RNF8. GIT2 likely promotes DNA repair through multiple mechanisms, including
      stabilization of BRCA1 in repair complexes; upregulation of repair proteins,
      including HMGN1 and RFC1; and regulation of poly(ADP-ribose) polymerase activity.
      Furthermore, GIT2-knockout mice demonstrated a greater susceptibility to DNA
      damage than their wild-type littermates. These results suggest that GIT2 plays an
      important role in MRE11/ATM/H2AX-mediated DNA damage responses. 

PMID- 25605335
TI  - Rbs1, a new protein implicated in RNA polymerase III biogenesis in yeast
      Saccharomyces cerevisiae.
AB  - Little is known about the RNA polymerase III (Pol III) complex assembly and its
      transport to the nucleus. We demonstrate that a missense cold-sensitive mutation,
      rpc128-1007, in the sequence encoding the C-terminal part of the second largest
      Pol III subunit, C128, affects the assembly and stability of the enzyme. The
      cellular levels and nuclear concentration of selected Pol III subunits were
      decreased in rpc128-1007 cells, and the association between Pol III subunits as
      evaluated by coimmunoprecipitation was also reduced. To identify the proteins
      involved in Pol III assembly, we performed a genetic screen for suppressors of
      the rpc128-1007 mutation and selected the Rbs1 gene, whose overexpression
      enhanced de novo tRNA transcription in rpc128-1007 cells, which correlated with
      increased stability, nuclear concentration, and interaction of Pol III subunits.
      The rpc128-1007 rbs1Delta double mutant shows a synthetic growth defect,
      indicating that rpc128-1007 and rbs1Delta function in parallel ways to negatively
      regulate Pol III assembly. Rbs1 physically interacts with a subset of Pol III
      subunits, AC19, AC40, and ABC27/Rpb5. Additionally, Rbs1 interacts with the Crm1
      exportin and shuttles between the cytoplasm and nucleus. We postulate that Rbs1
      binds to the Pol III complex or subcomplex and facilitates its translocation to
      the nucleus. 

PMID- 25605339
TI  - Arthroscopic ankle fusion for avascular necrosis of the talus.
AB  - BACKGROUND: Avascular necrosis (AVN) of the talus is a painful condition leading
      to destruction of the ankle-hindfoot complex. Moderate outcomes and high
      complication rates are reported in small numbers of advanced disease treated with
      tibiotalocalcaneal fusion, which has the additional disadvantage of sacrificing
      both the ankle and subtalar joints. The blood supply of the talus is tenuous, and
      open procedures risk further talar collapse by disrupting extraosseous vessels.
      This article reports the outcome of arthroscopic ankle fusion for late-stage AVN
      of the talus. Our hypothesis was that arthroscopic ankle fusion would relieve
      symptoms of advanced talar AVN, prevent collapse of the talus, and preserve the
      subtalar joint. METHODS: A cohort study was performed on 16 patients with talar
      AVN treated with arthroscopic ankle fusion. Our primary outcome was fusion rate.
      Secondary outcomes included perioperative complications, ongoing pain, and
      further operative intervention. All radiologic investigations were reported
      independently by a senior radiologist. The average age of the patients was 53.5
      years. The presumed causes of talar AVN were steroids, trauma, hematologic
      disorders, and alcoholism. The etiology was unknown in 7 patients. One patient
      was lost to follow-up. RESULTS: Clinical and radiologic fusion at the ankle joint
      was confirmed in 15 of 15 available patients. Thirteen patients reported
      resolution of pain at follow-up. Three patients had ongoing pain and underwent a
      subsequent successful subtalar fusion. CONCLUSIONS: Arthroscopic ankle fusion was
      a safe and reliable treatment of symptomatic advanced talar AVN. It was a
      minimally invasive procedure with minimal complication rate, preserving the talus
      and sparing the subtalar joint. LEVEL OF EVIDENCE: Level IV, retrospective case
      series.

PMID- 25605336
TI  - Muscle-derived extracellular signal-regulated kinases 1 and 2 are required for
      the maintenance of adult myofibers and their neuromuscular junctions.
AB  - The Ras-extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway appears to
      be important for the development, maintenance, aging, and pathology of mammalian
      skeletal muscle. Yet no gene targeting of Erk1/2 in muscle fibers in vivo has
      been reported to date. We combined a germ line Erk1 mutation with Cre-loxP Erk2
      inactivation in skeletal muscle to produce, for the first time, mice lacking
      ERK1/2 selectively in skeletal myofibers. Animals lacking muscle ERK1/2 displayed
      stunted postnatal growth, muscle weakness, and a shorter life span. Their muscles
      examined in this study, sternomastoid and tibialis anterior, displayed fragmented
      neuromuscular synapses and a mixture of modest fiber atrophy and loss but failed
      to show major changes in fiber type composition or absence of cell surface
      dystrophin. Whereas the lack of only ERK1 had no effects on the phenotypes
      studied, the lack of myofiber ERK2 explained synaptic fragmentation in the
      sternomastoid but not the tibialis anterior and a decrease in the expression of
      the acetylcholine receptor (AChR) epsilon subunit gene mRNA in both muscles. A
      reduction in AChR protein was documented in line with the above mRNA results.
      Evidence of partial denervation was found in the sternomastoid but not the
      tibialis anterior. Thus, myofiber ERK1/2 are differentially required for the
      maintenance of myofibers and neuromuscular synapses in adult mice. 

PMID- 25605340
TI  - Proximal phalanx and flexor digitorum longus tendon biomechanics in flexor to
      extensor tendon transfer.
AB  - BACKGROUND: The flexor to extensor transfer of the flexor digitorum longus (FDL)
      tendon has been a relatively common operative procedure for the treatment of a
      flexible hammer toe deformity and chronic metatarsophalangeal (MTP) joint
      dislocation. A possible complication of using the tunnel technique rather than
      the tendon splitting technique is iatrogenic fracture through the drilled tunnel
      site. The purpose of this investigation was to study the FDL tendon and proximal
      phalanx dimensions in the area of the transfer procedure in order to improve
      preoperative planning and minimize postoperative complications. Additionally,
      this study investigated the force necessary to create a fracture in a predrilled
      proximal phalanx and attempted to elucidate a relationship between that force and
      the percentage of bone remaining after the drilling process. METHODS: The
      proximal phalanx and FDL tendon of the second, third, and fourth toes from both
      the right and the left foot of 14 fresh frozen cadavers were dissected, and the
      digit was amputated at the MTP joint. A total of 84 toes (42 right, 42 left) were
      obtained from 14 cadavers. The diameter of the FDL tendon was measured, and the
      circumference and volume were calculated. Fourteen proximal phalanges of either
      the right or the left foot were then drilled with a 3.5-mm drill, as is often
      done in a tendon transfer procedure. The 14 nondrilled bones from the
      contralateral foot were used as matched controls. Radiographs were then taken of
      the proximal phalanges, and the dimensions of the drill tunnel and remaining bone
      were calculated. These measurements were used to calculate the volume of the
      bone, the volume of the drill tunnel, and the percentage of bone remaining after
      the drilling process. The bones were then tested for load-to-failure using a
      biomechanical loading apparatus. RESULTS: The average bone and tendon diameter
      measurements showed a gradual decrease in size from the second to the fourth
      digits. The bone removed by drilling the tunnel accounted for approximately 20%
      to 30% of the total volume of bone. Half of the bones fractured with forces
      between 100 and 200 N, and the majority of bones with a diameter of less than 6
      mm fractured with a force of less than 100 N. CONCLUSIONS: The average proximal
      phalanx and FDL tendon size both showed an overall decrease from the second to
      the fourth digit, albeit not symmetrically. The proximal phalanx diameter
      appeared to be the most important factor in determining the strength of the
      structure. CLINICAL RELEVANCE: Iatrogenic fracture may occur in proximal
      phalanges with a diameter of bone less than 6 mm, as there may not be adequate
      bone strength remaining to withstand postoperative forces.

PMID- 25605338
TI  - Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C
      Mutation (p.E591K).
AB  - PURPOSE: We have previously reported clinical features of two siblings, a sister
      with complete achromatopsia (ACHM) and a brother with incomplete ACHM, in a
      consanguineous Japanese family. With the current study, we intended to identify a
      disease-causing mutation in the siblings and to investigate why the phenotypes of
      the siblings differed. METHODS: We performed a comprehensive ophthalmic
      examination for each sibling and parent. Whole-exome and Sanger sequencing were
      performed on genomic DNA. Molecular modeling was analyzed in an in silico study.
      RESULTS: The ophthalmic examination revealed severe macular atrophy in the older
      female sibling at 30 years of age and mild macular atrophy in the brother at 26
      years of age. The genetic analysis identified a novel homozygous PDE6C mutation
      (p.E591K) as the disease-causing allele in the siblings. Each parent was
      heterozygous for the mutation. Molecular modeling showed that the mutation could
      cause a conformational change in the PDE6C protein and result in reduced
      phosphodiesterase activity. We also identified an OPN1SW mutation (p.G79R), which
      is associated with congenital tritan deficiencies, in the sister and the father
      but not in the brother. CONCLUSIONS: A novel homozygous PDE6C mutation was
      identified as the cause of ACHM. In addition, we identified an OPN1SW mutation in
      the sibling with complete ACHM, which might explain the difference in phenotype
      (complete versus incomplete ACHM) between the siblings.

PMID- 25605341
TI  - [Why and how I review articles submitted to Progres en urologie: opinion of the
      best reviewer in 2014].

PMID- 25605337
TI  - PCTK1 regulates integrin-dependent spindle orientation via protein kinase A
      regulatory subunit KAP0 and myosin X.
AB  - Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of
      spindle orientation. However, the signaling pathways that couple integrins to
      spindle orientation remain elusive. Here, we show that PCTAIRE-1 kinase (PCTK1),
      a member of the cyclin-dependent kinases (CDKs) whose function is poorly
      characterized, plays an essential role in this process. PCTK1 regulates spindle
      orientation in a kinase-dependent manner. Phosphoproteomic analysis together with
      an RNA interference screen revealed that PCTK1 regulates spindle orientation
      through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase
      A (PKA). This phosphorylation is dispensable for KAP0 dimerization and for PKA
      binding but is necessary for its interaction with myosin X, a regulator of
      spindle orientation. KAP0 binds to the FERM domain of myosin X and enhances the
      association of myosin X-FERM with beta1 integrin. This interaction between myosin
      X-FERM and beta1 integrin appeared to be crucial for spindle orientation control.
      We propose that PCTK1-KAP0-myosin X-beta1 integrin is a functional module
      providing a link between ECM and the actin cytoskeleton in the ECM-dependent
      control of spindle orientation. 

PMID- 25605342
TI  - [Negative effects on sexual function of medications for the treatment of lower
      urinary tract symptoms related to benign prostatic hyperplasia].
AB  - PURPOSE: The aim of this review is to discuss the negative effects on sexual
      function of medications for lower urinary tract symptoms secondary to benign
      prostatic hyperplasia (LUTS-BPH). METHODS: An international non-systematic
      literature review was performed. It included randomized trials of seven drugs of
      interest and the summaries of the characteristics of these products. This work
      did not aim comparison between the drugs. RESULTS: Only maximal reported
      frequencies are presented in this abstract. With prolonged-release alfuzosin,
      they were 2.8% vs. 1.3% for erectile dysfunction, compared to placebo and 1% vs.
      0% for ejaculatory dysfunction. With doxazosin, the incidence was 5.8% vs. 3.3%
      for erectile dysfunction, 3.6% vs. 1.9% for reduced libido and 0.4% vs. 1.4% for
      ejaculatory disorders. The incidence of ejaculatory disorders with tamsulosin,
      was 11% vs. <1% with the placebo and with silodosin, it was 28.1% vs. 1.1%. With
      finasteride, at 12 months, the highest frequency was 9% vs. 5% for erectile
      dysfunction, 4.4% vs. 1.5% for ejaculatory disorders and 6.4% vs. 3.4% for
      reduced libido. At 24 months, for dutatsteride, frequencies were 7.3% vs. 4.0%
      for erectile dysfunction, 2.2% vs. 0.8% for ejaculatory disorders and 4.2% vs.
      2.1% for reduced libido. For tadalafil, a phosphodiesterase-5 inhibitor, and
      tolerodine, an anticholinergic drug, no negative effect on ejaculation or libido
      has been reported. For plant extracts, no sexual adverse effects (AEs) were
      reported among the most common AEs. CONCLUSION: The medications for LUTS-BPH may
      alter erection, ejaculation or libido. A greater knowledge of the adverse effects
      of each of these drugs could guide physicians in the clinical management of men
      with BPH-LUTS.

PMID- 25605343
TI  - [Cost-effectiveness of transurethral resection of the bladder with blue light in
      patients with non muscle invasive bladder cancer in France].
AB  - OBJECTIVE: Photodynamic diagnosis after instillation of hexylaminolevulinate
      (Hexvix((r))) during transurethral resection of the bladder (TURB) helps in the
      detection of tumors and results in a reduction of recurrence. The medical and
      economic impact of fluorescence compared to conventional white light TURB needed
      to be analyzed in the French healthcare system. The aim of this study was to
      evaluate the medical and economic impact of the blue light TURB in the treatment
      of NMIBC. MATERIALS AND METHODS: A cost-utility model, based on data from the
      literature and expert opinions, combining a decision tree and a Markov model was
      used to simulate the initial management after a first TURB of all new patients
      diagnosed with symptoms consistent with NMIBC and outcomes at short and long
      terms. In this model, the initial TURB could be achieved either with fluorescence
      in addition to white light, or with white light only. The main criteria of the
      model was based on the quality adjusted life years (QALY). The economic
      evaluation focused on the direct costs. The test's results and costs were
      determined from diagnosis until death of patients. RESULTS: The use of
      photodynamic diagnosis during TURB resulted in an improvement in QALYs (0.075)
      and a reduction of ? 670 of the costs compared to the conventional treatment with
      white light. Thus, the blue light resection was defined as a strategy called
      "dominant" over the TURB in white light. CONCLUSION: In the context of the French
      health system, the model of the study showed that the blue light cystoscopy
      during TURB was associated with increased QALYs and reduced health spending. This
      kind of result is rare in oncology. This health economic analysis confirms the
      interest of hexylaminolevulinate acid in initial management of NMIBC, according
      to studies conducted in United Kingdom, Italy and Poland.

PMID- 25605344
TI  - Pulmonary nodule size evaluation with chest tomosynthesis and CT: a phantom
      study.
AB  - OBJECTIVE: We compared digital tomosynthesis (TOMO) and chest CT in terms of
      assessing the sizes of nodules located in zones where evaluation by simple
      radiography is limited. METHODS: A total of 48 images comprising phantom nodules
      of four sizes in six different locations were used. Nodule size measurement
      errors for measurements using TOMO and CT images compared with the actual size
      from each observer were calculated. The inter- and intraobserver repeatability of
      the measured values and the agreement between the two techniques were assessed
      using the method described by Bland and Altman. RESULTS: The mean measurement
      errors for all of the nodules and four observers were -0.84 mm [standard
      deviation (SD), 0.60 mm] on TOMO and -0.18 mm (SD, 0.71 mm) on CT images. The
      mean measurement errors for the different observers ranged from -1.11 to -0.55 mm
      for TOMO and from -0.39 to 0.08 mm for CT. Assessing the agreement between nodule
      size measurements using TOMO and CT resulted in mean measurement errors of -0.65
      mm, with a 95% limit of agreement of -2.53 to 1.22 mm for comparison of TOMO with
      CT. CONCLUSION: Our results suggest that nodule sizes obtained using TOMO and
      chest CT are comparable, even for nodules located in areas where the size
      measurement is limited on simple radiography. ADVANCES IN KNOWLEDGE: TOMO and CT
      can be used interchangeably, even for nodules located in a blind area on simple
      radiography.

PMID- 25605345
TI  - Use of tomotherapy in treatment of synchronous bilateral breast cancer:
      dosimetric comparison study.
AB  - OBJECTIVE: Synchronous malignancy in both breasts is a rare incidence. The
      present study aims at dosimetric comparison of conventional bitangential
      radiotherapy (RT) technique with conventional [field-in-field (FIF)] and
      rotational [Helical TomoTherapy((r)) and TomoDirectTM (TD); Accuray Inc.,
      Sunnyvale, CA] intensity-modulated RT for patients with synchronous bilateral
      breast cancer (SBBC). METHODS: CT data sets of 10 patients with SBBC were
      selected for the present study. RT was planned for all patients on both sides to
      whole breast and/or chest wall using the above-mentioned techniques. Six females
      with breast conservation on at least one side also had a composite plan along
      with tumour bed (TB) boost using sequential electrons for bitangential and FIF
      techniques or sequential helical tomotherapy (HT) boost (for TD) or simultaneous
      integrated boost (SIB) for HT. RESULTS: All techniques produced acceptable target
      coverage. The hotspot was significantly lower with FIF technique and HT but
      higher with TD. For the organs at risk doses, HT resulted in significant
      reduction of the higher dose volumes. Similarly, TD resulted in significant
      reduction of the mean dose to the heart and total lung by reducing the lower dose
      volumes. All techniques of delivering boost to the TB were comparable in terms of
      target coverage. HT-SIB markedly reduced mean doses to the total lung and heart
      by specifically lowering the higher dose volumes. CONCLUSION: This study
      demonstrates the cardiac and pulmonary sparing ability of tomotherapy in the
      setting of SBBC. ADVANCES IN KNOWLEDGE: This is the first study demonstrating
      feasibility of treatment of SBBC using tomotherapy.

PMID- 25605346
TI  - Model-based vs hybrid iterative reconstruction technique in ultralow-dose
      submillisievert CT colonography.
AB  - OBJECTIVE: To compare image quality of different reconstruction techniques in
      submillisievert ultralow-dose CT colonography (CTC) and to correlate colonic
      findings with subsequent optical colonoscopy. METHODS: 58 patients underwent
      ultralow-dose CTC. The images were reconstructed with filtered back projection
      (FBP), hybrid iterative reconstruction (HIR) or model-based iterative
      reconstruction (MBIR) techniques. In each segment, endoluminal noise (expressed
      as standard deviation of endoluminal density) was measured and image quality was
      rated on a five-point Likert scale by two independent readers. Colonic lesions
      were evaluated in consensus and correlated with subsequent optical colonoscopy
      where possible. RESULTS: The estimated radiation dose was 0.41 +/- 0.05 mSv for
      the supine and 0.42 +/- 0.04 mSv for the prone acquisitions. In the endoluminal
      view, the image quality was rated better in HIR, whereas better scores were
      obtained in MBIR in the cross-sectional view, where the endoluminal noise was the
      lowest (p < 0.0001). Five (26%) polyps were not identified using both computer
      aided detection and endoluminal inspection in FBP images vs only one (5%) in MBIR
      and none in HIR images. CONCLUSION: This study showed that in submillisievert
      ultralow-dose CTC, the image quality for the endoluminal view is better when HIR
      is used, whereas MBIR yields superior images for the cross-sectional view. The
      inferior quality of images reconstructed with FBP may result in decreased
      detection of colonic lesions. ADVANCES IN KNOWLEDGE: Radiation dose from CTC can
      be safely reduced <1 mSv for both positions when iterative reconstruction is
      used. MBIR provides better image quality in the cross-sectional view and HIR in
      the endoluminal view.

PMID- 25605347
TI  - Computed diffusion-weighted MRI for prostate cancer detection: the influence of
      the combinations of b-values.
AB  - OBJECTIVE: To evaluate the influence of the combinations of b-values on computed
      diffusion-weighted images (cDWIs) for prostate cancer (PCa) detection at b = 2000
      s mm(-2). METHODS: Diffusion-weighted imaging (DWIs) for 31 patients with PCa
      (65.2 +/- 7.1 years) were obtained pre-operatively at different b-values (0, 100,
      500, 1000 and 2000 s mm(-2)) on a 3-T MRI. cDWIs at b = 2000 were generated by
      using six b-value combinations: 0-100 s mm(-2) (cDWI0-100); 0-500 s mm(-2) (cDWI0
      500); 100-500 s mm(-2) (cDWI100-500); 0-1000 s mm(-2) (cDWI0-1000); 100-1000 s
      mm(-2) (cDWI100-1000); and 500-1000 s mm(-2) (cDWI500-1000). These cDWIs and
      measured DWIs with b = 2000 s mm(-2) (mDWI2000) were evaluated in this setting.
      To assess image quality for each DWI, contrast ratios (CRs) of cancerous and non
      cancerous lesions were evaluated. To compare the detectability of PCa for each
      DWI, receiver operating characteristic analysis was used. RESULTS: CRs of all
      cDWIs were significantly higher than those of mDWI2000 (p < 0.05). Areas under
      the curve of cDWI0-100 (0.62) and cDWI0-500 (0.65) were significantly smaller (p
      < 0.05) than those of others (cDWI100-500, 0.72; cDWI0-1000, 0.73; cDWI100-1000,
      0.71; cDWI500-1000, 0.74; mDWI2000, 0.72). CONCLUSION: The combinations of b
      values influenced image quality and diagnostic ability of cDWIs for PCa
      detection. The combinations of b >= 100 and b >= 500 s mm(-2), as well as b = 0
      and b = 1000 s mm(-2), were optimal in this study. ADVANCES IN KNOWLEDGE: For
      generating the useful cDWI for PCa detection, radiologists should take care of
      the combination of b-values when including low b-values.

PMID- 25605348
TI  - Photothermoelectric and photovoltaic effects both present in MoS2.
AB  - As a finite-energy-bandgap alternative to graphene, semiconducting molybdenum
      disulfide (MoS2) has recently attracted extensive interest for energy and sensor
      applications. In particular for broad-spectral photodetectors, multilayer MoS2 is
      more appealing than its monolayer counterpart. However, little is understood
      regarding the physics underlying the photoresponse of multilayer MoS2. Here, we
      employ scanning photocurrent microscopy to identify the nature of photocurrent
      generated in multilayer MoS2 transistors. The generation and transport of
      photocurrent in multilayer MoS2 are found to differ from those in other low
      dimensional materials that only contribute with either photovoltaic effect (PVE)
      or photothermoelectric effect (PTE). In multilayer MoS2, the PVE at the MoS2
      metal interface dominates in the accumulation regime whereas the hot-carrier
      assisted PTE prevails in the depletion regime. Besides, the anomalously large
      Seebeck coefficient observed in multilayer MoS2, which has also been reported by
      others, is caused by hot photo-excited carriers that are not in thermal
      equilibrium with the MoS2 lattice. 

PMID- 25605349
TI  - Barley: a translational model for adaptation to climate change.
AB  - Barley (Hordeum vulgare ssp. vulgare) is an excellent model for understanding
      agricultural responses to climate change. Its initial domestication over 10
      millennia ago and subsequent wide migration provide striking evidence of
      adaptation to different environments, agro-ecologies and uses. A bottleneck in
      the selection of modern varieties has resulted in a reduction in total genetic
      diversity and a loss of specific alleles relevant to climate-smart agriculture.
      However, extensive and well-curated collections of landraces, wild barley
      accessions (H. vulgare ssp. spontaneum) and other Hordeum species exist and are
      important new allele sources. A wide range of genomic and analytical tools have
      entered the public domain for exploring and capturing this variation, and
      specialized populations, mutant stocks and transgenics facilitate the connection
      between genetic diversity and heritable phenotypes. These lay the biological,
      technological and informational foundations for developing climate-resilient
      crops tailored to specific environments that are supported by extensive
      environmental and geographical databases, new methods for climate modelling and
      trait/environment association analyses, and decentralized participatory
      improvement methods. Case studies of important climate-related traits and their
      constituent genes - including examples that are indicative of the complexities
      involved in designing appropriate responses - are presented, and key developments
      for the future highlighted.

PMID- 25605350
TI  - In vitro susceptibility testing of eravacycline is unaffected by medium age and
      nonstandard assay parameters.
AB  - Eravacycline is a fluorocycline antibiotic in phase 3 clinical development for
      complicated intra-abdominal and urinary tract infections. To support its clinical
      development, a study was conducted to evaluate the effects of various
      susceptibility test parameters on the MIC values for aerobic bacteria. The
      results showed that eravacycline appears to be largely unaffected by medium age,
      medium additives, and other nonstandard assay conditions. 

PMID- 25605351
TI  - Examining the use of ceftaroline in the treatment of Streptococcus pneumoniae
      meningitis with reference to human cathelicidin LL-37.
AB  - Five cases of bacterial meningitis treated with ceftaroline (4 Streptococcus
      pneumoniae and 1 Staphylococcus aureus) are summarized here. The pharmacodynamics
      of human cathelicidin LL-37 and ceftaroline were evaluated against S. pneumoniae.
      Patients who received ceftaroline 600 mg every 8 h (q8h) (1 S. aureus and 3 S.
      pneumoniae) were successfully treated; treatment failed in 1 patient with S.
      pneumoniae who received 600 mg q12h. Ceftaroline increased the negative surface
      charge and sensitized S. pneumoniae to killing by LL-37, a peptide implicated in
      blood-brain barrier defense. 

PMID- 25605353
TI  - Novel phage lysin capable of killing the multidrug-resistant gram-negative
      bacterium Acinetobacter baumannii in a mouse bacteremia model.
AB  - Acinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is
      now recognized as one of the more common nosocomial pathogens. Because most
      clinical isolates are found to be multidrug resistant, alternative therapies need
      to be developed to control this pathogen. We constructed a bacteriophage genomic
      library based on prophages induced from 13 A. baumannii strains and screened it
      for genes encoding bacteriolytic activity. Using this approach, we identified 21
      distinct lysins with different activities and sequence diversity that were
      capable of killing A. baumannii. The lysin (PlyF307) displaying the greatest
      activity was further characterized and was shown to efficiently kill (>5-log-unit
      decrease) all tested A. baumannii clinical isolates. Treatment with PlyF307 was
      able to significantly reduce planktonic and biofilm A. baumannii both in vitro
      and in vivo. Finally, PlyF307 rescued mice from lethal A. baumannii bacteremia
      and as such represents the first highly active therapeutic lysin specific for
      Gram-negative organisms in an array of native lysins found in Acinetobacter
      phage. 

PMID- 25605352
TI  - Subtle changes in endochin-like quinolone structure alter the site of inhibition
      within the cytochrome bc1 complex of Plasmodium falciparum.
AB  - The cytochrome bc1 complex (cyt bc1) is the third component of the mitochondrial
      electron transport chain and is the target of several potent antimalarial
      compounds, including the naphthoquinone atovaquone (ATV) and the 4(1H)-quinolone
      ELQ-300. Mechanistically, cyt bc1 facilitates the transfer of electrons from
      ubiquinol to cytochrome c and contains both oxidative (Qo) and reductive (Qi)
      catalytic sites that are amenable to small-molecule inhibition. Although many
      antimalarial compounds, including ATV, effectively target the Qo site, it has
      been challenging to design selective Qi site inhibitors with the ability to
      circumvent clinical ATV resistance, and little is known about how chemical
      structure contributes to site selectivity within cyt bc1. Here, we used the
      proposed Qi site inhibitor ELQ-300 to generate a drug-resistant Plasmodium
      falciparum clone containing an I22L mutation at the Qi region of cyt b. Using
      this D1 clone and the Y268S Qo mutant strain, P. falciparum Tm90-C2B, we created
      a structure-activity map of Qi versus Qo site selectivity for a series of
      endochin-like 4(1H)-quinolones (ELQs). We found that Qi site inhibition was
      associated with compounds containing 6-position halogens or aryl 3-position side
      chains, while Qo site inhibition was favored by 5,7-dihalogen groups or 7
      position substituents. In addition to identifying ELQ-300 as a preferential Qi
      site inhibitor, our data suggest that the 4(1H)-quinolone scaffold is compatible
      with binding to either site of cyt bc1 and that minor chemical changes can
      influence Qo or Qi site inhibition by the ELQs. 

PMID- 25605354
TI  - Impact of the combination of daptomycin and trimethoprim-sulfamethoxazole on
      clinical outcomes in methicillin-resistant Staphylococcus aureus infections.
AB  - Complicated Staphylococcus aureus infections, including bacteremia, are often
      associated with treatment failures, prolonged hospital stays, and the emergence
      of resistance to primary and even secondary therapies. Daptomycin is commonly
      used as salvage therapy after vancomycin failure for the treatment of methicillin
      resistant S. aureus (MRSA) infections. Unfortunately, the emergence of daptomycin
      resistance, especially in deep-seated infections, has been reported, prompting
      the need for alternative or combination therapy. Numerous antibiotic combinations
      with daptomycin have been investigated clinically and in vitro. Of interest, the
      combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved
      to be rapidly bactericidal in vitro to strains that are both susceptible and
      nonsusceptible to daptomycin. However, to date, there is limited clinical
      evidence supporting the use of this combination. This was a multicenter,
      retrospective case series of patients treated with the combination of daptomycin
      and TMP-SMX for at least 72 h. The objective of this study was to describe the
      safety and effectiveness of this regimen in clinical practice. The most commonly
      stated reason that TMP-SMX was added to daptomycin was persistent bacteremia
      and/or progressive signs and symptoms of infection. After the initiation of
      combination therapy, the median time to clearance of bacteremia was 2.5 days.
      Microbiological eradication was demonstrated in 24 out of 28 patients, and in
      vitro synergy was demonstrated in 17 of the 17 recovered isolates. Further
      research with this combination is necessary to describe the optimal role and its
      impact on patient outcomes. 

PMID- 25605355
TI  - Streptococcus gallolyticus subsp. gallolyticus from human and animal origins:
      genetic diversity, antimicrobial susceptibility, and characterization of a
      vancomycin-resistant calf isolate carrying a vanA-Tn1546-like element.
AB  - The aim of this work was to characterize the antibiotic susceptibility and
      genetic diversity of 41 Streptococcus gallolyticus subsp. gallolyticus isolates:
      18 isolates obtained from animals and 23 human clinical isolates. Antibiotic
      susceptibility was determined by the semiautomatic Wider system and genetic
      diversity by pulsed-field gel electrophoresis (PFGE) with SmaI. Animal isolates
      grouped separately in the PFGE analysis, but no statistical differences in
      antimicrobial resistance were found between the two groups. The LMG 17956
      sequence type 28 (ST28) strain recovered from the feces of a calf exhibited high
      levels of resistance to vancomycin and teicoplanin (MIC, >=256 mg/liter). Its
      glycopeptide resistance mechanism was characterized by Southern blot
      hybridization and a primer-walking strategy, and finally its genome, determined
      by whole-genome sequencing, was compared with four closely related S.
      gallolyticus subsp. gallolyticus genomes. Hybridization experiments demonstrated
      that a Tn1546-like element was integrated into the bacterial chromosome. In
      agreement with this finding, whole-genome sequencing confirmed a partial deletion
      of the vanY-vanZ region and partial duplication of the vanH gene. The comparative
      genomic analyses revealed that the LMG 17956 ST28 strain had acquired an
      unusually high number of transposable elements and had experienced extensive
      chromosomal rearrangements, as well as gene gain and loss events. In conclusion,
      S. gallolyticus subsp. gallolyticus isolates from animals seem to belong to
      lineages separate from those infecting humans. In addition, we report a
      glycopeptide-resistant isolate from a calf carrying a Tn1546-like element
      integrated into its chromosome. 

PMID- 25605356
TI  - Small-molecule inhibitors of Staphylococcus aureus RnpA-mediated RNA turnover and
      tRNA processing.
AB  - New agents are urgently needed for the therapeutic treatment of Staphylococcus
      aureus infections. In that regard, S. aureus RNase RnpA may represent a promising
      novel dual-function antimicrobial target that participates in two essential
      cellular processes, RNA degradation and tRNA maturation. Accordingly, we
      previously used a high-throughput screen to identify small-molecule inhibitors of
      the RNA-degrading activity of the enzyme and showed that the RnpA inhibitor
      RNPA1000 is an attractive antimicrobial development candidate. In this study, we
      used a series of in vitro and cellular assays to characterize a second RnpA
      inhibitor, RNPA2000, which was identified in our initial screening campaign and
      is structurally distinct from RNPA1000. In doing so, it was found that S. aureus
      RnpA does indeed participate in 5'-precursor tRNA processing, as was previously
      hypothesized. Further, we show that RNPA2000 is a bactericidal agent that
      inhibits both RnpA-associated RNA degradation and tRNA maturation activities both
      in vitro and within S. aureus. The compound appears to display specificity for
      RnpA, as it did not significantly affect the in vitro activities of unrelated
      bacterial or eukaryotic ribonucleases and did not display measurable human
      cytotoxicity. Finally, we show that RNPA2000 exhibits antimicrobial activity and
      inhibits tRNA processing in efflux-deficient Gram-negative pathogens. Taken
      together, these data support the targeting of RnpA for antimicrobial development
      purposes, establish that small-molecule inhibitors of both of the functions of
      the enzyme can be identified, and lend evidence that RnpA inhibitors may have
      broad-spectrum antimicrobial activities. 

PMID- 25605357
TI  - Dissemination of blaOXA-23 in Acinetobacter spp. in China: main roles of
      conjugative plasmid pAZJ221 and transposon Tn2009.
AB  - Production of the OXA-23 carbapenemase is the most common reason for the
      increasing carbapenem resistance in Acinetobacter spp. This study was conducted
      to reveal the genetic basis of blaOXA-23 dissemination in Acinetobacter spp. in
      China. A total of 63 carbapenem-resistant OXA-23-producing Acinetobacter sp.
      isolates, representing different backgrounds, were selected from 28 hospitals in
      18 provinces for this study. Generally, two patterns of plasmids carrying blaOXA
      23 were detected according to S1-nuclease pulsed-field gel electrophoresis and
      Southern blot hybridization. A ca. 78-kb plasmid, designated pAZJ221, was found
      in 23 Acinetobacter baumannii and three Acinetobacter nosocomialis isolates,
      while a novel ca. 50-kb plasmid was carried by only two other A. baumannii
      isolates. Three of these isolates had an additional copy of blaOXA-23 on the
      chromosome. Transformation of the two plasmids succeeded, but only pAZJ221 was
      conjugative. Plasmid pAZJ221 was sequenced completely and found to carry no
      previously known resistance genes except blaOXA-23. The blaOXA-23 gene of the
      remaining 35 isolates was chromosome borne. The blaOXA-23 genetic environments
      were correlated with Tn2009 in 57 isolates, Tn2008 in 5 isolates, and Tn2006 in 1
      isolate. The MIC values for the carbapenems with these isolates were not
      significantly associated with the genomic locations or the copy numbers of blaOXA
      23. Overall, these observations suggest that the plasmid pAZJ221 and Tn2009 have
      effectively contributed to the wide dissemination of blaOXA-23 in Acinetobacter
      spp. in China and that horizontal gene transfer may play an important role in
      dissemination of the blaOXA-23 gene. 

PMID- 25605358
TI  - VT-1161 dosed once daily or once weekly exhibits potent efficacy in treatment of
      dermatophytosis in a guinea pig model.
AB  - Current therapies used to treat dermatophytoses such as onychomycosis are
      effective but display room for improvement in efficacy, safety, and convenience
      of dosing. We report here that the investigational agent VT-1161 displays potent
      in vitro antifungal activity against dermatophytes, with MIC values in the range
      of <=0.016 to 0.5 MUg/ml. In pharmacokinetic studies supporting testing in a
      guinea pig model of dermatophytosis, VT-1161 plasma concentrations following
      single oral doses were dose proportional and persisted at or above the MIC values
      for at least 48 h, indicating potential in vivo efficacy with once-daily and
      possibly once-weekly dosing. Subsequently, in a guinea pig dermatophytosis model
      utilizing Trichophyton mentagrophytes and at oral doses of 5, 10, or 25 mg/kg of
      body weight once daily or 70 mg/kg once weekly, VT-1161 was statistically
      superior to untreated controls in fungal burden reduction (P < 0.001) and
      improvement in clinical scores (P < 0.001). The efficacy profile of VT-1161 was
      equivalent to those for doses and regimens of itraconazole and terbinafine except
      that VT-1161 was superior to itraconazole when each drug was dosed once weekly (P
      < 0.05). VT-1161 was distributed into skin and hair, with plasma and tissue
      concentrations in all treatment and regimen groups ranging from 0.8 to 40 MUg/ml
      (or MUg/g), at or above the MIC against the isolate used in the model (0.5
      MUg/ml). These data strongly support the clinical development of VT-1161 for the
      oral treatment of onychomycosis using either once-daily or once-weekly dosing
      regimens. 

PMID- 25605359
TI  - Antimicrobial activity of solithromycin against serotyped macrolide-resistant
      Streptococcus pneumoniae isolates collected from U.S. medical centers in 2012.
AB  - Solithromycin, a next-generation macrolide and novel fluoroketolide, was tested
      against a 2012 collection of serotyped U.S. macrolide-resistant Streptococcus
      pneumoniae isolates associated with community-acquired bacterial pneumonia
      (CABP). Against all 272 isolates, solithromycin demonstrated high potency
      (MIC50/90, 0.06/0.25 MUg/ml), and it inhibited all strains at MICs of <=0.5
      MUg/ml, including the two most prevalent macrolide-resistant serotypes (19A and
      35B). These data support the continued clinical development of solithromycin for
      the treatment of multidrug-resistant CABP. 

PMID- 25605360
TI  - Analysis of embCAB mutations associated with ethambutol resistance in multidrug
      resistant mycobacterium tuberculosis isolates from China.
AB  - Ethambutol (EMB) plays a pivotal role in the chemotherapy of drug-resistant
      tuberculosis (TB), including multidrug-resistant tuberculosis (MDR-TB).
      Resistance to EMB is considered to be caused by mutations in the embCAB operon
      (embC, embA, and embB). In this study, we analyzed the embCAB mutations among 139
      MDR-TB isolates from China and found a possible association between embCAB operon
      mutation and EMB resistance. Our data indicate that 56.8% of MDR-TB isolates are
      resistant to EMB, and 82.2% of EMB-resistant isolates belong to the Beijing
      family. Overall, 110 (79.1%) MDR-TB isolates had at least one mutation in the
      embCAB operon. The majority of mutations were present in the embB gene and the
      embA upstream region, which also displayed significant correlations with EMB
      resistance. The most common mutations occurred at codon 306 in embB (embB306),
      followed by embB406, embA(-16), and embB497. Mutations at embB306 were associated
      with EMB resistance. DNA sequencing of embB306-497 was the best strategy for
      detecting EMB resistance, with 89.9% sensitivity, 58.3% specificity, and 76.3%
      accuracy. Additionally, embB306 had limited value as a candidate predictor for
      EMB resistance among MDR-TB infections in China. 

PMID- 25605361
TI  - In vivo effect of flucloxacillin in experimental endocarditis caused by mecC
      positive staphylococcus aureus showing temperature-dependent susceptibility in
      vitro.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene (mecC
      MRSA) exhibited at 37 degrees C MICs of oxacillin close to those of methicillin
      susceptible S. aureus (MSSA). We investigated whether at this temperature, mecC
      MRSA strains respond to flucloxacillin treatment like MSSA strains, using a rat
      model of endocarditis. Flucloxacillin (human-like kinetics of 2 g intravenously
      every 6 h) cured 80 to 100% of aortic vegetations infected with five different
      mecC-MRSA strains. These results suggest that mecC-MRSA infections may
      successfully respond to treatment with beta-lactams. 

PMID- 25605362
TI  - Dissemination of high-risk clones of extensively drug-resistant Pseudomonas
      aeruginosa in colombia.
AB  - The ability of Pseudomonas aeruginosa to develop resistance to most
      antimicrobials represents an important clinical threat worldwide. We report the
      dissemination in several Colombian hospitals of two predominant lineages of
      extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains.
      These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235
      and harbor blaVIM-2 on a class 1 integron and blaKPC-2 on a Tn4401 transposon,
      respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of
      ST111, was identified. Clonal dissemination and the presence of mobile genetic
      elements likely explain the successful spread of XDR P. aeruginosa strains in
      Colombia. 

PMID- 25605363
TI  - Bis-benzimidazole hits against Naegleria fowleri discovered with new high
      throughput screens.
AB  - Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute
      fatal disease known as primary amoebic meningoencephalitis (PAM). The major
      problem for infections with any pathogenic FLA is a lack of effective
      therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new
      drugs that are potent and have rapid onset of action are needed to enhance the
      treatment regimens for PAM. Diamidines have demonstrated potency against multiple
      pathogens, including FLA, and are known to cross the blood-brain barrier to cure
      other protozoan diseases of the central nervous system. Therefore, amidino
      derivatives serve as an important chemotype for discovery of new drugs. In this
      study, we validated two new in vitro assays suitable for medium- or high
      throughput drug discovery and used these for N. fowleri. We next screened over
      150 amidino derivatives of multiple structural classes and identified two hit
      series with nM potency that are suitable for further lead optimization as new
      drugs for this neglected disease. These include both mono- and diamidino
      derivatives, with the most potent compound (DB173) having a 50% inhibitory
      concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues
      with IC50s of <1 MUM, with many of these having reasonable selectivity indices.
      The most potent hits were >500 times more potent than pentamidine. In summary,
      the mono- and diamidino derivatives offer potential for lead optimization to
      develop new drugs to treat central nervous system infections with N. fowleri. 

PMID- 25605364
TI  - Potentiation of antibacterial activity of the MB-1 siderophore-monobactam
      conjugate using an efflux pump inhibitor.
AB  - Preliminary enthusiasm over the encouraging spectrum and in vitro activities of
      siderophore conjugates, such as MB-1, was recently tempered by unexpected
      variability in in vivo efficacy. The need for these conjugates to compete for
      iron with endogenously produced siderophores has exposed a significant liability
      for this novel antibacterial strategy. Here, we have exploited dependence on
      efflux for siderophore secretion in Pseudomonas aeruginosa and provide evidence
      that efflux inhibition may circumvent this in vivo-relevant resistance liability.

PMID- 25605365
TI  - Antimicrobial activity against intraosteoblastic Staphylococcus aureus.
AB  - Although Staphylococcus aureus persistence in osteoblasts, partly as small-colony
      variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the
      intracellular activity of antimicrobials is not currently considered in the
      choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials
      were evaluated for their intraosteoblastic activity and their impact on the
      intracellular emergence of SCVs in an ex vivo osteoblast infection model.
      Osteoblastic MG63 cells were infected for 2 h with HG001 S. aureus. After killing
      the remaining extracellular bacteria with lysostaphin, infected cells were
      incubated for 24 h with antimicrobials at the intraosseous concentrations reached
      with standard therapeutic doses. Intracellular bacteria and SCVs were then
      quantified by plating cell lysates. A bactericidal effect was observed with
      fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and
      clindamycin, with reductions in the intracellular inocula of -2.5, -3.1, -3.9, 
      4.2, -4.9, -4.9, and -5.2 log10 CFU/100,000 cells, respectively (P < 10(-4)).
      Conversely, a bacteriostatic effect was observed with ceftaroline and
      teicoplanin, whereas vancomycin and daptomycin had no significant impact on
      intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin
      significantly limited intracellular SCV emergence. Overall, ofloxacin was the
      only molecule to combine an excellent intracellular activity while limiting the
      emergence of SCVs. These data provide a basis for refining the choice of
      antibiotics to prioritise in the management of BJI, justifying the combination of
      a fluoroquinolone for its intracellular activity with an anti-biofilm molecule,
      such as rifampin. 

PMID- 25605367
TI  - Effects of fasting and feeding on the fast-start swimming performance of southern
      catfish Silurus meridionalis.
AB  - This study investigated the effects of fasting and feeding on the fast-start
      escape swimming performance of juvenile southern catfish Silurus meridionalis, a
      sit-and-wait forager that encounters extreme fasting and famine frequently during
      its lifespan. Ten to 30 days of fasting resulted in no significant change in most
      of the variables measured in the fast-start response except a 20-30% decrease in
      the escape distance during the first 120 ms (D120ms ) relative to the control
      group (48 h after feeding). The ratio of the single-bend (SB) response (lower
      energetic expenditure) to the double-bend (DB) response increased significantly
      from 0% in the control group to 75 and 82.5% in the 20 and 30 day fasting groups,
      respectively. Satiated feeding (25% of body mass) resulted in a significantly
      lower (36.6%) maximum linear velocity (Vmax ) and a significantly lower (43.3%)
      D120ms than in non-fed fish (control group, 48 h after feeding). Half-satiated
      feeding (12.5% of body mass), however, showed no significant effects on any of
      the measured variables of the fast-start response relative to control fish. It is
      suggested that the increase in the ratio of SB:DB responses with fasting in S.
      meridionalis may reflect a trade-off between energy conservation and maintaining
      high Vmax , while variables of fast-start performance were more sensitive to
      feeding than fasting might be an adaptive strategy to their foraging mode and
      food availability in their habitat.

PMID- 25605366
TI  - PmrD is required for modifications to escherichia coli endotoxin that promote
      antimicrobial resistance.
AB  - In Salmonella enterica, PmrD is a connector protein that links the two-component
      systems PhoP-PhoQ and PmrA-PmrB. While Escherichia coli encodes a PmrD homolog,
      it is thought to be incapable of connecting PhoPQ and PmrAB in this organism due
      to functional divergence from the S. enterica protein. However, our laboratory
      previously observed that low concentrations of Mg(2+), a PhoPQ-activating signal,
      leads to the induction of PmrAB-dependent lipid A modifications in wild-type E.
      coli (C. M. Herrera, J. V. Hankins, and M. S. Trent, Mol Microbiol 76:1444-1460,
      2010, http://dx.doi.org/10.1111/j.1365-2958.2010.07150.x). These modifications
      include phosphoethanolamine (pEtN) and 4-amino-4-deoxy-l-arabinose (l-Ara4N),
      which promote bacterial resistance to cationic antimicrobial peptides (CAMPs)
      when affixed to lipid A. Here, we demonstrate that pmrD is required for
      modification of the lipid A domain of E. coli lipopolysaccharide (LPS) under low
      Mg(2+) growth conditions. Further, RNA sequencing shows that E. coli pmrD
      influences the expression of pmrA and its downstream targets, including genes
      coding for the modification enzymes that transfer pEtN and l-Ara4N to the lipid A
      molecule. In line with these findings, a pmrD mutant is dramatically impaired in
      survival compared with the wild-type strain when exposed to the CAMP polymyxin B.
      Notably, we also reveal the presence of an unknown factor or system capable of
      activating pmrD to promote lipid A modification in the absence of the PhoPQ
      system. These results illuminate a more complex network of protein interactions
      surrounding activation of PhoPQ and PmrAB in E. coli than previously understood. 

PMID- 25605368
TI  - Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in
      previously treated patients with cutaneous T-cell lymphoma.
AB  - This phase 1/2 study evaluated the efficacy of mogamulizumab, a defucosylated,
      humanized, anti-CC chemokine receptor 4 monoclonal antibody, in 41 pretreated
      patients with cutaneous T-cell lymphoma. No dose-limiting toxicity was observed
      and the maximum tolerated dose was not reached in phase 1 after IV infusion of
      mogamulizumab (0.1, 0.3, and 1.0 mg/kg) once weekly for 4 weeks followed by a 2
      week observation. In phase 2, patients were dosed with 1.0 mg/kg mogamulizumab
      according to the same schedule for the first course followed by infusion every 2
      weeks during subsequent courses until disease progression. The most frequent
      treatment-emergent adverse events were nausea (31.0%), chills (23.8%), headache
      (21.4%), and infusion-related reaction (21.4%); the majority of events were grade
      1/2. There were no significant hematologic effects. Among 38 evaluable patients,
      the overall response rate was 36.8%: 47.1% in Sezary syndrome (n = 17) and 28.6%
      in mycosis fungoides (n = 21). Eighteen of 19 (94.7%) patients with >=B1 blood
      involvement had a response in blood, including 11 complete responses. Given the
      safety and efficacy of mogamulizumab, phase 3 investigation of mogamulizumab is
      warranted in cutaneous T-cell lymphoma patients. This trial was registered at
      www.clinicaltrials.gov as #NCT00888927. 

PMID- 25605369
TI  - CD24(hi)CD27+ and plasmablast-like regulatory B cells in human chronic graft
      versus-host disease.
AB  - Interleukin 10 (IL-10)-producing B cells (regulatory B cells [Bregs]) regulate
      autoimmunity in mice and humans, and a regulatory role of IL-10-producing plasma
      cells has been described in mice. Dysfunction of B cells that maintain
      homeostasis may play a role in the pathogenesis of chronic graft-versus-host
      disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a
      relation between decreased Breg frequencies and cGVHD severity. An impaired
      ability of B cells to produce IL-10, possibly linked to poor signal transducer
      and activator of transcription 3 and extracellular signal-regulated kinase
      phosphorylation, was found in patients with active cGVHD. IL-10 production was
      not confined to a single B-cell subset, but enriched in both the CD24(hi)CD27(+)
      and CD27(hi)CD38(hi) plasmablast B-cell compartments. In vitro plasmablast
      differentiation increased the frequency of IL-10-producing B cells. We confirmed
      that allogeneic transplant recipients had an impaired reconstitution of the
      memory B-cell pool. cGVHD patients had less CD24(hi)CD27(+) B cells and IL-10
      producing CD24(hi)CD27(+) B cells. Patients with cGVHD had increased plasmablast
      frequencies but decreased IL-10-producing plasmablasts. These results suggest a
      role of CD24(hi)CD27(+) B-cell and plasmablast-derived IL-10 in the regulation of
      human cGVHD. 

PMID- 25605370
TI  - FLT3-ITD and TLR9 use Bruton tyrosine kinase to activate distinct transcriptional
      programs mediating AML cell survival and proliferation.
AB  - Acute myeloid leukemia (AML) is driven by niche-derived and cell-autonomous
      stimuli. Although many cell-autonomous disease drivers are known, niche-dependent
      signaling in the context of the genetic disease heterogeneity has been difficult
      to investigate. Here, we analyzed the role of Bruton tyrosine kinase (BTK) in
      AML. BTK was frequently expressed, and its inhibition strongly impaired the
      proliferation and survival of AML cells also in the presence of bone marrow
      stroma. By interactome analysis, (phospho)proteomics, and transcriptome
      sequencing, we characterized BTK signaling networks. We show that BTK-dependent
      signaling is highly context dependent. In Fms-like tyrosine kinase 3 internal
      tandem duplication (FLT3-ITD)-positive AML, BTK mediates FLT3-ITD-dependent Myc
      and STAT5 activation, and combined targeting of FLT3-ITD and BTK showed additive
      effects. In Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)
      negative AML, BTK couples Toll-like receptor 9 (TLR9) activation to nuclear
      factor kappaBeta and STAT5. Both BTK-dependent transcriptional programs were
      relevant for cell cycle progression and apoptosis regulation. Thus, we identify
      context-dependent oncogenic driver events that may guide subtype-specific
      treatment strategies and, for the first time, point to a role of TLR9 in AML.
      Clinical evaluation of BTK inhibitors in AML seems warranted. 

PMID- 25605371
TI  - Evidence-based focused review of the role of radiation therapy in the treatment
      of early-stage Hodgkin lymphoma.

PMID- 25605373
TI  - How I treat mixed-phenotype acute leukemia.
AB  - Mixed-phenotype acute leukemia (MPAL) encompasses a heterogeneous group of rare
      leukemias in which assigning a single lineage of origin is not possible. A
      variety of different terms and classification systems have been used historically
      to describe this entity. MPAL is currently defined by a limited set of lineage
      specific markers proposed in the 2008 World Health Organization monograph on
      classification of tumors of hematopoietic and lymphoid tissues. In adult
      patients, MPAL is characterized by relative therapeutic resistance that may be
      attributed in part to the high proportion of patients with adverse cytogenetic
      abnormalities. No prospective, controlled trials exist to guide therapy. The
      limited available data suggest that an "acute lymphoblastic leukemia-like"
      regimen followed by allogeneic stem-cell transplant may be advisable; addition of
      a tyrosine kinase inhibitor in patients with t(9;22) translocation is
      recommended. The role of immunophenotypic and genetic markers in guiding
      chemotherapy choice and postremission strategy, as well as the utility of
      targeted therapies in non-Ph-positive MPALs is unknown. 

PMID- 25605372
TI  - MOZ regulates B-cell progenitors and, consequently, Moz haploinsufficiency
      dramatically retards MYC-induced lymphoma development.
AB  - The histone acetyltransferase MOZ (MYST3, KAT6A) is the target of recurrent
      chromosomal translocations fusing the MOZ gene to CBP, p300, NCOA3, or TIF2 in
      particularly aggressive cases of acute myeloid leukemia. In this study, we report
      the role of wild-type MOZ in regulating B-cell progenitor proliferation and
      hematopoietic malignancy. In the EMU-Myc model of aggressive pre-B/B-cell
      lymphoma, the loss of just one allele of Moz increased the median survival of
      mice by 3.9-fold. MOZ was required to maintain the proliferative capacity of B
      cell progenitors, even in the presence of c-MYC overexpression, by directly
      maintaining the transcriptional activity of genes required for normal B-cell
      development. Hence, B-cell progenitor numbers were significantly reduced in Moz
      haploinsufficient animals. Interestingly, we find a significant overlap in genes
      regulated by MOZ, mixed lineage leukemia 1, and mixed lineage leukemia 1 cofactor
      menin. This includes Meis1, a TALE class homeobox transcription factor required
      for B-cell development, characteristically upregulated as a result of MLL1
      translocations in leukemia. We demonstrate that MOZ localizes to the Meis1 locus
      in pre-B-cells and maintains Meis1 expression. Our results suggest that even
      partial inhibition of MOZ may reduce the proliferative capacity of MEIS1, and HOX
      driven lymphoma and leukemia cells. 

PMID- 25605375
TI  - Mechanical properties of nickel-graphene composites synthesized by
      electrochemical deposition.
AB  - Graphene (Gr) nanosheets with multilayer structures were dispersed in a nickel
      (Ni) plating solution by using a surfactant with a magnetic stirring method. Gr
      nanosheets were incorporated into a Ni matrix through a plating process to form
      Ni-Gr composites on a target substrate. Gr nanosheets were uniformly dispersed in
      the Ni matrix, and the oxygen radicals present in the Gr were reduced during the
      electro-deposition process. The incorporation of Gr in the Ni matrix increases
      both the inter-planar spacing and the degree of preferred orientation of
      crystalline Ni. With the addition of Gr content as low as 0.05 g L(-1), the
      elastic modulus and hardness of the Ni-Gr composites reach 240 GPa and 4.6 GPa,
      respectively, which are about 1.7 and 1.2 times that of the pure Ni deposited
      under the same condition. The enhancement in mechanical properties of the
      composites is attributed to the preferred formation of the Ni crystalline phases
      in its (111) plane, the high interaction between Ni and Gr and the prevention of
      the dislocation sliding in the Ni matrix by the Gr. The results suggest that the
      method of using Gr directly instead of graphene oxide (GO) is efficient and
      scalable. 

PMID- 25605374
TI  - Analytical study of robustness of a negative feedback oscillator by
      multiparameter sensitivity.
AB  - BACKGROUND: One of the distinctive features of biological oscillators such as
      circadian clocks and cell cycles is robustness which is the ability to resume
      reliable operation in the face of different types of perturbations. In the
      previous study, we proposed multiparameter sensitivity (MPS) as an intelligible
      measure for robustness to fluctuations in kinetic parameters. Analytical
      solutions directly connect the mechanisms and kinetic parameters to dynamic
      properties such as period, amplitude and their associated MPSs. Although negative
      feedback loops are known as common structures to biological oscillators, the
      analytical solutions have not been presented for a general model of negative
      feedback oscillators. RESULTS: We present the analytical expressions for the
      period, amplitude and their associated MPSs for a general model of negative
      feedback oscillators. The analytical solutions are validated by comparing them
      with numerical solutions. The analytical solutions explicitly show how the
      dynamic properties depend on the kinetic parameters. The ratio of a threshold to
      the amplitude has a strong impact on the period MPS. As the ratio approaches to
      one, the MPS increases, indicating that the period becomes more sensitive to
      changes in kinetic parameters. We present the first mathematical proof that the
      distributed time-delay mechanism contributes to making the oscillation period
      robust to parameter fluctuations. The MPS decreases with an increase in the
      feedback loop length (i.e., the number of molecular species constituting the
      feedback loop). CONCLUSIONS: Since a general model of negative feedback
      oscillators was employed, the results shown in this paper are expected to be true
      for many of biological oscillators. This study strongly supports that the
      hypothesis that phosphorylations of clock proteins contribute to the robustness
      of circadian rhythms. The analytical solutions give synthetic biologists some
      clues to design gene oscillators with robust and desired period.

PMID- 25605376
TI  - The 5-year outcome of patients having incomplete colonoscopy.
AB  - AIM: Incomplete colonoscopy indicated for the detection of neoplasia occurs in 2
      23% of patients, but there is little information on the long-term outcome of such
      patients. METHOD: All patients who underwent colonoscopy over 5 years at the
      Royal Liverpool University Hospital with a follow-up of up to 5 years were
      identified. RESULTS: The risk of colorectal cancer (CRC) was 2.9% (312/10 580)
      for all patients undergoing colonoscopy. For a failed colonoscopy, the risk was
      five-fold higher [14.3% (99/693)]. The mean age of the patients was 61 years and
      58% were female. Following incomplete colonoscopy the risk of finding additional
      CRC, advanced colonic neoplasia and extracolonic neoplasia on subsequent
      investigation was 6.2%, 3.2% and 1.9%. The diagnostic yield on subsequent
      investigation for CRC or colonic polyps was 7% for repeat colonoscopy, 13.4% for
      computed tomography colonography, 10.3% for standard computed tomography and 1.8%
      for barium enema. In the 363 patients who were not offered a subsequent
      investigation, there was no further instance of CRC or CRC-related mortality over
      a 36-month period. CONCLUSION: Although the risk of CRC is higher in patients who
      have had a failed colonoscopy, a protocol approach of subsequent investigation
      should not replace clinical assessment on whether another test is necessary in
      the light of the good outcome of patients who were not subsequently investigated.

PMID- 25605377
TI  - Controllable n-type doping on CVD-grown single- and double-layer graphene
      mixture.
AB  - n-Type doping of mixed single- and double-layer graphene grown by chemical vapor
      deposition (CVD) using decamethyl-cobaltocene reveals a local-quasilinear
      relationship between the work function and the logarithm of the dopant solution
      concentration. The relationship that arises from bandgap opening is deduced by
      comparing the relationship between the two factors for single- or double-layer
      graphene. This work has extensive applicability and practical significance in
      doping CVD-grown graphene. 

PMID- 25605378
TI  - Design of transcription regulating riboswitches.
AB  - In this chapter, we review both computational and experimental aspects of de novo
      RNA sequence design. We give an overview of currently available design software
      and their limitations, and discuss the necessary setup to experimentally validate
      proper function in vitro and in vivo. We focus on transcription-regulating
      riboswitches, a task that has just recently lead to first successful designs of
      such RNA elements. 

PMID- 25605379
TI  - Ligand-dependent exponential amplification of self-replicating RNA enzymes.
AB  - A general analytical method for the detection of target ligands has been
      developed, based on a special class of self-replicating aptazymes. These
      "autocatalytic aptazymes" are generated by linking an aptamer domain to the
      catalytic domain of a self-replicating RNA enzyme. Ligand-dependent self
      replication of RNA proceeds in a self-sustained manner, undergoing exponential
      amplification at a constant temperature without the assistance of any proteins or
      other biological materials. The rate of exponential amplification is dependent on
      the concentration of the ligand, thus enabling quantitative ligand detection.
      This system has the potential to detect any ligand that can be recognized by an
      aptamer, including small molecules and proteins. The instability of RNA in
      biological samples due to the presence of ribonucleases can be overcome by
      employing the enantiomeric L-RNA form of the self-replicating enzyme. Methods for
      real-time fluorescence monitoring over the course of exponential amplification
      are currently being developed. 

PMID- 25605380
TI  - Design of modular "plug-and-play" expression platforms derived from natural
      riboswitches for engineering novel genetically encodable RNA regulatory devices.
AB  - Genetically encodable RNA devices that directly detect small molecules in the
      cellular environment are of increasing interest for a variety of applications
      including live cell imaging and synthetic biology. Riboswitches are naturally
      occurring sensors of intracellular metabolites, primarily found in the bacterial
      mRNA leaders and regulating their expression. These regulatory elements are
      generally composed of two domains: an aptamer that binds a specific effector
      molecule and an expression platform that informs the transcriptional or
      translational machinery. While it was long established that riboswitch aptamers
      are modular and portable, capable of directing different output domains including
      ribozymes, switches, and fluorophore-binding modules, the same has not been
      demonstrated until recently for expression platforms. We have engineered and
      validated a set of expression platforms that regulate transcription through a
      secondary structural switch that can host a variety of different aptamers,
      including those derived through in vitro selection methods, to create novel
      chimeric riboswitches. These synthetic switches are capable of a highly specific
      regulatory response both in vitro and in vivo. Here we present the methodology
      for the design and engineering of chimeric switches using biological expression
      platforms. 

PMID- 25605381
TI  - Integrating and amplifying signal from riboswitch biosensors.
AB  - Biosensors offer a built-in energy supply and inherent sensing machinery that
      when exploited correctly may surpass traditional sensors. However, biosensor
      systems have been hindered by a narrow range of ligand detection capabilities, a
      relatively low signal output, and their inability to integrate multiple signals.
      Integration of signals could increase the specificity of the sensor and enable
      detection of a combination of ligands that may indicate environmental or
      developmental processes when detected together. Amplifying biosensor signal
      output will increase detector sensitivity and detection range. Riboswitches offer
      the potential to widen the diversity of ligands that may be detected, and
      advances in synthetic biology are illuminating myriad possibilities in signal
      processing using an orthogonal parts-based engineering approach. In this chapter,
      we describe the design, building, and testing of a riboswitch-based Boolean logic
      AND gate in bacteria, where an output requires the activation of two
      riboswitches, and the biological circuitry required to amplify the output of the
      AND gate using natural extracellular bacterial communication signals to "wire"
      cells together. 

PMID- 25605382
TI  - Simple identification of two causes of noise in an aptazyme system by monitoring
      cell-free transcription.
AB  - Aptazymes are artificially synthesized ribozymes that catalyze reactions in
      response to ligand binding. Certain types of aptazymes can be utilized as RNA
      based regulators of gene expression. These aptazymes contain a sequestered
      ribosome-binding site (rbs) and release the rbs through self-cleavage in response
      to ligand binding, inducing the expression of the downstream gene. One of the
      most important properties of aptazymes as gene expression regulators is their
      signal-to-noise ratio (S/N ratio), the ratio of target expression in the presence
      of ligand to that in the absence of ligand. One strategy to improve the S/N ratio
      is to decrease the noise (expression in the absence of ligand) due to leaky
      translation without rbs release or ligand-independent rbs release. In this
      chapter, we describe an easy method to identify the main cause of noise using a
      cell-free reconstituted transcription-translation system, an ideal platform for
      the quantitative understanding of biochemical reactions because researchers can
      strictly control the experimental conditions and the concentrations of all
      components. This knowledge would be useful for designing aptazymes with high S/N
      ratios. 

PMID- 25605383
TI  - Engineering of ribosomal shunt-modulating eukaryotic ON riboswitches by using a
      cell-free translation system.
AB  - A number of natural and artificial bacterial riboswitches have been reported thus
      far. However, they generally function only in bacteria, not in eukaryotes. This
      is because of the differences of expression mechanisms (transcription,
      translation, and so on) between these two main types of organisms. For example,
      the mechanism of translation initiation is quite different between bacteria and
      eukaryotes, especially in ribosome loading on mRNA. While the bacterial ribosome
      binds to a well-conserved, internal sequence some bases before the start codon to
      initiate translation, the eukaryotic one is loaded on the 5' terminus with the
      help of certain eukaryotic initiation factors. This means not only that bacterial
      riboswitches regulating translation initiation are not available in eukaryotic
      translation systems, but also that it is physically difficult to construct
      eukaryotic ON riboswitches that regulate the eukaryotic canonical translation
      initiation, because an aptamer cannot be inserted upstream of the ribosome
      loading site. However, the mechanism of noncanonical translation initiation via
      "ribosomal shunt" enables us to design translation initiation-modulating
      (specifically, ribosomal shunt-modulating) eukaryotic ON riboswitches. This
      chapter describes a facile method for engineering these ribosomal shunt
      modulating eukaryotic ON riboswitches by using a cell-free translation system.
      Because these riboswitches do not require hybridization switching thanks to a
      unique shunting mechanism, they have the major advantages of a low energy
      requirement for upregulation and relatively straightforward design over common
      hybridization switch-based ON riboswitches. 

PMID- 25605384
TI  - Live-cell imaging of mammalian RNAs with Spinach2.
AB  - The ability to monitor RNAs of interest in living cells is crucial to
      understanding the function, dynamics, and regulation of this important class of
      molecules. In recent years, numerous strategies have been developed with the goal
      of imaging individual RNAs of interest in living cells, each with their own
      advantages and limitations. This chapter provides an overview of current methods
      of live-cell RNA imaging, including a detailed discussion of genetically encoded
      strategies for labeling RNAs in mammalian cells. This chapter then focuses on the
      development and use of "RNA mimics of GFP" or Spinach technology for tagging
      mammalian RNAs and includes a detailed protocol for imaging 5S and CGG60 RNA with
      the recently described Spinach2 tag. 

PMID- 25605385
TI  - In vitro analysis of riboswitch-Spinach aptamer fusions as metabolite-sensing
      fluorescent biosensors.
AB  - The development of fluorescent biosensors has been motivated by the interest to
      monitor and measure the levels of specific metabolites in live cells in real
      time. Common approaches include fusing a protein-based receptor to fluorescent
      proteins or synthesizing a small molecule reactive probe. Natural metabolite
      sensing riboswitches also have been used in reporter-based systems that take
      advantage of ligand-dependent regulation of downstream gene expression. More
      recently, it has been shown that RNA-based fluorescent biosensors can be
      generated by fusing a riboswitch aptamer to the in vitro selected Spinach
      aptamer, which binds a cell-permeable and conditionally fluorescent molecule.
      Here, we describe methods to design, prepare, and analyze riboswitch-Spinach
      aptamer fusion RNAs for ligand-dependent activation of fluorescence in vitro.
      Examples of procedures to measure fluorescence activation, ligand binding
      selectivity and affinity, and binding kinetics are given for a cyclic di-GMP
      responsive biosensor. The relative ease of in vitro RNA synthesis and
      purification should make this method accessible to other researchers interested
      in developing riboswitch-based fluorescent biosensors. 

PMID- 25605386
TI  - Using Spinach aptamer to correlate mRNA and protein levels in Escherichia coli.
AB  - In vivo gene expression measurements have traditionally relied on fluorescent
      proteins such as green fluorescent protein (GFP) with the help of high
      sensitivity equipment such as flow cytometers. However, fluorescent proteins
      report only on the protein level inside the cell without giving direct
      information about messenger RNA (mRNA) production. In 2011, an aptamer termed
      Spinach was presented that acts as an RNA mimic of GFP when produced in
      Escherichia coli and mammalian cells. It was later shown that coexpression of a
      red fluorescent protein (mRFP1) and the Spinach aptamer, when included into the
      same gene expression cassette, could be utilized for parallel in vivo
      measurements of mRNA and protein production. As accurate characterization of
      component biological parts is becoming increasingly important for fields such as
      synthetic biology, Spinach in combination with mRFP1 provide a great tool for the
      characterization of promoters and ribosome binding sites. In this chapter, we
      discuss how live-cell imaging and flow cytometry can be used to detect and
      measure fluorescence produced in E. coli cells by different constructs that
      contain the Spinach aptamer and the mRFP1 gene. 

PMID- 25605387
TI  - Monitoring mRNA and protein levels in bulk and in model vesicle-based artificial
      cells.
AB  - With rising interest in utilizing cell-free gene expression systems in bottom-up
      synthetic biology projects, novel labeling tools need to be developed to
      accurately report the dynamics and performance of the biosynthesis machinery
      operating in various reaction conditions. Monitoring the transcription activity
      has been simplified by the Spinach technology, an RNA aptamer that emits
      fluorescence upon binding to a small organic dye. Recently, we tracked the
      fluorescence of Spinach-tagged messenger RNA (mRNA) and its translation product
      the yellow fluorescent protein (YFP), both synthesized in the protein synthesis
      using recombinant elements system from a DNA template. Building on our previous
      study, we describe here an improved Spinach reporter with modified flanking
      sequences that confer higher propensity for aptamer folding and, thus, enhanced
      fluorescence brightness. Hence, the kinetics of mRNA and YFP production could be
      simultaneously monitored with unprecedented sensitivity. A combination of
      methodologies, comprising RNA gel analysis, real-time quantitative polymerase
      chain reaction, absorbance measurements, and fluorescence correlation
      spectroscopy, was used to convert fluorescence intensity units into absolute
      concentrations of transcript and YFP translational product. Furthermore, we
      demonstrated that the new Spinach construct greatly enhanced mRNA detection when
      gene expression was confined inside self-assembled lipid vesicles. Therefore, we
      argue that this assay could be used to evaluate systematically the performance of
      transcription and translation in model vesicle-based artificial cells. 

PMID- 25605388
TI  - Design, synthesis, and application of Spinach molecular beacons triggered by
      strand displacement.
AB  - We describe design parameters for the synthesis and analytical application of a
      label-free RNA molecular beacon, termed Spinach.ST. The RNA aptamer Spinach
      fluoresces upon binding the small-molecule fluorophore DFHBI ((Z)-4-(3,5-difluoro
      4-hydroxybenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one). Spinach has been
      reengineered by extending its 5'- and 3'-ends to create Spinach.ST, which is
      predicted to fold into an inactive conformation that fails to bind DHFBI.
      Hybridization of a trigger oligonucleotide to a designed toehold on Spinach.ST
      initiates toehold-mediated strand displacement and restores the DFHBI-binding,
      fluorescence-enhancing conformation of Spinach. The versatile Spinach.ST sensor
      can detect DNA or RNA trigger sequences and can readily distinguish single
      nucleotide mismatches in the trigger toehold. Primer design techniques are
      described that augment amplicons produced by enzymatic amplification with
      Spinach.ST triggers. Interaction between these triggers and Spinach.ST molecular
      beacons leads to the real-time, sequence-specific quantitation of these
      amplicons. The use of Spinach.ST with isothermal amplification reactions such as
      nucleic acid sequence-based amplification (NASBA) may enable point-of-care
      applications. The same design principles could also be used to adapt Spinach
      reporters to the assay of nonnucleic acid analytes in trans. 

PMID- 25605389
TI  - Using riboswitches to regulate gene expression and define gene function in
      mycobacteria.
AB  - Mycobacteria include both environmental species and many pathogenic species such
      as Mycobacterium tuberculosis, an intracellular pathogen that is the causative
      agent of tuberculosis in humans. Inducible gene expression is a powerful tool for
      examining gene function and essentiality, both in in vitro culture and in host
      cell infections. The theophylline-inducible artificial riboswitch has recently
      emerged as an alternative to protein repressor-based systems. The riboswitch is
      translationally regulated and is combined with a mycobacterial promoter that
      provides transcriptional control. We here provide methods used by our laboratory
      to characterize the riboswitch response to theophylline in reporter strains,
      recombinant organisms containing riboswitch-regulated endogenous genes, and in
      host cell infections. These protocols should facilitate the application of both
      existing and novel artificial riboswitches to the exploration of gene function in
      mycobacteria. 

PMID- 25605390
TI  - Controlling expression of genes in the unicellular alga Chlamydomonas reinhardtii
      with a vitamin-repressible riboswitch.
AB  - Chloroplast genomes of land plants and algae contain generally between 100 and
      150 genes. These genes are involved in plastid gene expression and photosynthesis
      and in various other tasks. The function of some chloroplast genes is still
      unknown and some of them appear to be essential for growth and survival.
      Repressible and reversible expression systems are highly desirable for functional
      and biochemical characterization of these genes. We have developed a genetic tool
      that allows one to regulate the expression of any coding sequence in the
      chloroplast genome of the unicellular alga Chlamydomonas reinhardtii. Our system
      is based on vitamin-regulated expression of the nucleus-encoded chloroplast Nac2
      protein, which is specifically required for the expression of any plastid gene
      fused to the psbD 5'UTR. With this approach, expression of the Nac2 gene in the
      nucleus and, in turn, that of the chosen chloroplast gene artificially driven by
      the psbD 5'UTR, is controlled by the MetE promoter and Thi4 riboswitch, which can
      be inactivated in a reversible way by supplying vitamin B12 and thiamine to the
      growth medium, respectively. This system opens interesting possibilities for
      studying the assembly and turnover of chloroplast multiprotein complexes such as
      the photosystems, the ribosome, and the RNA polymerase. It also provides a way to
      overcome the toxicity often associated with the expression of proteins of
      biotechnological interest in the chloroplast. 

PMID- 25605391
TI  - Conditional control of gene expression by synthetic riboswitches in Streptomyces
      coelicolor.
AB  - Here we provide a step-by-step protocol for the application of synthetic
      theophylline-dependent riboswitches for conditional gene expression in
      Streptomyces coelicolor. Application of the method requires a sequence of only
      ~85 nt to be inserted between the transcriptional start site and the start codon
      of a gene of interest. No auxiliary factors are needed. All tested riboswitch
      variants worked well in concert with the promoters galP2, ermEp1, and SF14.
      Moreover, they allowed theophylline-dependent expression not only of the
      heterologous beta-glucuronidase reporter gene but also of dagA, an endogenous
      agarase gene. The right combination of the tested promoters with the riboswitch
      variants allows for the adjustment of the desired dynamic range of regulation in
      a highly specific and dose-dependent manner and underlines the orthogonality of
      riboswitch regulation. We anticipate that any additional natural or synthetic
      promoter can be combined with the presented riboswitches. Moreover, this system
      should easily be transferable to other Streptomyces species, and most likely to
      any other genetically manipulable bacteria.

PMID- 25605392
TI  - Engineering of ribozyme-based aminoglycoside switches of gene expression by in
      vivo genetic selection in Saccharomyces cerevisiae.
AB  - Synthetic RNA-based switches are a growing class of genetic controllers applied
      in synthetic biology to engineer cellular functions. In this chapter, we detail a
      protocol for the selection of posttranscriptional controllers of gene expression
      in yeast using the Schistosoma mansoni hammerhead ribozyme as a central catalytic
      unit. Incorporation of a small molecule-sensing aptamer domain into the ribozyme
      renders its activity ligand-dependent. Aptazymes display numerous advantages over
      conventional protein-based transcriptional controllers, namely, the use of little
      genomic space for encryption, their modular architecture allowing for easy
      reprogramming to new inputs, the physical linkage to the message to be
      controlled, and the ability to function without protein cofactors. Herein, we
      describe the method to select ribozyme-based switches of gene expression in
      Saccharomyces cerevisiae that we successfully implemented to engineer neomycin-
      and theophylline-responsive switches. We also highlight how to adapt the protocol
      to screen for switches responsive to other ligands. Reprogramming of the sensor
      unit and incorporation into any RNA of interest enables the fulfillment of a
      variety of regulatory functions. However, proper functioning of the aptazyme is
      largely dependent on optimal connection between the aptamer and the catalytic
      core. We obtained functional switches from a pool of variants carrying randomized
      connection sequences by an in vivo selection in MaV203 yeast cells that allows
      screening of a large sequence space of up to 1*10(9) variants. The protocol given
      explains how to construct aptazyme libraries, carry out the in vivo selection and
      characterize novel ON- and OFF-switches. 

PMID- 25605393
TI  - Kinetic folding design of aptazyme-regulated expression devices as riboswitches
      for metabolic engineering.
AB  - Recent developments in the fields of synthetic biology and metabolic engineering
      have opened the doors for the microbial production of biofuels and other valuable
      organic compounds. There remain, however, significant metabolic hurdles to the
      production of these compounds in cost-effective quantities. This is due, in part,
      to mismatches between the metabolic engineer's desire for high yields and the
      microbe's desire to survive. Many valuable compounds, or the intermediates
      necessary for their biosynthesis, prove deleterious at the desired production
      concentrations. One potential solution to these toxicity-related issues is the
      implementation of nonnative dynamic genetic control mechanisms that sense
      excessively high concentrations of metabolic intermediates and respond
      accordingly to alleviate their impact. One potential class of dynamic regulator
      is the riboswitch: cis-acting RNA elements that regulate the expression of
      downstream genes based on the presence of an effector molecule. Here, we present
      combined methods for constructing aptazyme-regulated expression devices (aREDs)
      through computational cotranscriptional kinetic folding design and experimental
      validation. These approaches can be used to engineer aREDs within novel genetic
      contexts for the predictable, dynamic regulation of gene expression in vivo. 

PMID- 25605394
TI  - Riboselector: riboswitch-based synthetic selection device to expedite evolution
      of metabolite-producing microorganisms.
AB  - Many successful metabolic engineering projects have utilized evolutionary
      approaches, which consist of generating phenotypic diversity and screening for
      desired phenotype. Since conventional screening methods suffer from low
      throughput and limited target metabolites, a universal high-throughput screening
      platform for selection of improved strains should be developed to facilitate
      evolution of metabolite high producer. Recently, riboswitches have received
      attention as attractive sensor-actuator hybrids that can control gene expression
      in response to intracellular metabolite concentration. Our group developed a
      riboswitch-based selection device called "Riboselector" which can give a growth
      advantage to metabolite-overproducing strains by modulating expression of a
      selectable marker gene. We applied the device to expedite evolution of lysine
      producing Escherichia coli, and the selected strain showed a dramatic improvement
      of lysine production compared to its parental strain. Moreover, a tryptophan
      responsive Riboselector was also developed using synthetic tryptophan aptamer. In
      this chapter, we provide a step-by-step overview of developing synthetic RNA
      devices comprising a riboswitch and a selection module that specifically sense
      inconspicuous metabolites and enrich high producer strains out of library. 

PMID- 25605395
TI  - Fluorescence assays for monitoring RNA-ligand interactions and riboswitch
      targeted drug discovery screening.
AB  - Riboswitches and other noncoding regulatory RNA are intriguing targets for the
      development of therapeutic agents. A significant challenge in the drug discovery
      process, however, is the identification of potent compounds that bind the target
      RNA specifically and disrupt its function. Essential to this process is an
      effectively designed cascade of screening assays. A screening cascade for
      identifying compounds that target the T box riboswitch antiterminator element is
      described. In the primary assays, moderate to higher throughput screening of
      compound libraries is achieved by combining the sensitivity of fluorescence
      techniques with functionally relevant assays. Active compounds are then validated
      and the binding to target RNA further characterized in secondary assays. The
      cascade of assays monitor ligand-induced changes in the steady-state fluorescence
      of an attached dye or internally incorporated 2-aminopurine; the fluorescence
      anisotropy of an RNA complex; and, the thermal denaturation fluorescence profile
      of a fluorophore-quencher labeled RNA. While the assays described have been
      developed for T box riboswitch-targeted drug discovery, the fluorescence methods
      and screening cascade design principles can be applied to drug discovery efforts
      targeted toward other medicinally relevant noncoding RNA. 

PMID- 25605396
TI  - Monitoring ribosomal frameshifting as a platform to screen anti-riboswitch drug
      candidates.
AB  - Riboswitches are regions within mRNAs that can regulate downstream expression of
      genes through metabolite-induced alteration of their secondary structures. Due to
      the significant association of bacterial essential or virulence genes, bacterial
      riboswitches have become promising targets for development of putative
      antibacterial drugs. However, most of the screening systems to date are based on
      in vitro or bacterial systems, lacking the possibility to preobserve the adverse
      effects to the host's translation machinery. This chapter describes a novel
      screening method based on monitoring the riboswitch-induced -1 ribosomal
      frameshifting (-1 FS) efficiency in a mammalian cell-free lysate system using
      preQ1 class-I (preQ1-I) riboswitches as model target. 

PMID- 25605397
TI  - Methods in Enzymology. Riboswitches as targets and tools. Preface.

PMID- 25605398
TI  - High electric conductivity of liquid crystals formed by ordered self-assembly of
      nonionic surfactant N,N-bis(2-hydroxyethyl)dodecanamide in water.
AB  - This work reports the ordered self-assembly of nonconductive small molecules that
      achieved extra high conductivity, thereby stating an convenient approach for
      constructing a biofriendly soft material that is suitable to be used as
      implantable biosensors and electro-stimulated drug delivery systems. The
      microstructure and the conductive mechanism were investigated in detail by
      combining experimental methods and molecular simulation. This research
      demonstrated that self-assembly of amide groups with delocalized electrons into
      pi-stacked arrays exhibited high mobilities for charge carriers. The excellent
      biocompatibility and processability of soft materials such as liquid crystals
      ensure that the system has high potential in the advance fields of biosensors and
      drug delivery devices. 

PMID- 25605399
TI  - Fluorescent nanosensors via photoinduced polymerization of hydrophobic inorganic
      quantum dots for the sensitive and selective detection of nitroaromatics.
AB  - We developed an efficient one-pot strategy for the preparation of hydrophilic
      amine-functionalized nanocomposites by using hydrophobic fluorescence quantum
      dots ZnS:Mn(2+)@allyl mercaptan (QDs@AM) as building blocks through novel light
      induced in situ polymerization. The average size of as-prepared hydrophilic
      nanocomposites was ~50 nm, which could be further tuned by varying the
      concentrations of the monomers. Importantly, these nanocomposites were further
      utilized for the facile, highly sensitive, and selective detection of
      nitroaromatics. The linear ranges for 2,4,6-trinitrotoluene (TNT) and 2,4,6
      trinitrophenol (TNP) lie in 0.01-0.5 MUg/mL and 0.05-8.0 MUg/mL, respectively,
      barely interfered with by other nitroaromatics such as 2,4-dinitrotoluene (DNT)
      and nitrobenzene (NB). Moreover, the novel surface modification method developed
      here offered a general strategy for fabricating hydrophobic nanocomposites with
      hydrophilic properties and indicated various potential applications including
      sensing and imaging. 

PMID- 25605400
TI  - Unexpected metal-free transformation of gem-Dibromomethylenes to ketones under
      acetylation conditions.
AB  - Novel conditions for the transformation of gem-dibromomethylenes to ketones are
      described. gem-Dibromo compounds were treated with acetic anhydride and
      triethylamine in dichloromethane/water at room temperature under an air
      atmosphere to give the corresponding ketones in moderate yields. A radical
      mechanism is proposed based on experimental results. 

PMID- 25605401
TI  - [Orthopedic update--orthopedic tumors].

PMID- 25605403
TI  - Toll-like receptor 2 subfamily gene polymorphisms are associated with Bacillus
      Calmette-Guerin osteitis following newborn vaccination.
AB  - AIM: Toll-like receptor (TLR) 1, 2, 6 and 10, the TLR2 subfamily, are known to be
      associated with immunity against tuberculosis. We evaluated whether polymorphisms
      in genes encoding TLR1, TLR2 and TLR6 were associated with osteitis in infants
      who received the Bacillus Calmette-Guerin (BCG) vaccination soon after birth.
      METHODS: Blood samples from 132 adults aged 21-49 who had BCG osteitis in early
      childhood were analysed in a controlled study for TLR1 T1805G (rs5743618), TLR2
      G2258A (rs5743708) and TLR6 C745T (rs5743810) gene single nucleotide
      polymorphisms. RESULTS: The frequencies of the variant genotypes differed between
      the cases and controls: 11.4% versus 5.7% for TLR2 G2258A (p = 0.033) and 77.3%
      versus 61.6% for TLR6 C745T (p = 0.001). The TLR2 and TLR6 variant genotypes were
      associated with a higher risk of BCG osteitis, with adjusted odds ratios (aOR) of
      2.154 (95%CI 1.026-4.521) and 1.907 (95%CI 1.183-3.075), respectively. The
      frequency of the TLR1 T1805G variant genotype was 19.7% in the cases and 33.6% in
      the controls (p = 0.003). The TLR1 variant genotype was associated with a lower
      risk of BCG osteitis (aOR 0.554, 95%CI 0.336-0.911). CONCLUSION: Gene
      polymorphisms that regulate the function of the TLR2 subfamily play a role in the
      development of BCG osteitis in vaccinated infants.

PMID- 25605402
TI  - Fecal calprotectin as a biomarker of intestinal graft versus host disease after
      allogeneic hematopoietic stem cell transplantation.
AB  - The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on
      clinical symptoms and histological findings. In clinical practice, it is often
      difficult to decide whether abdominal symptoms in an allogeneic transplant
      recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful
      in establishing the diagnosis, but endoscopy is not always possible to perform
      due to poor general condition of the patients. No biomarkers are routinely used
      to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in
      our study was to find out whether determination of the concentrations of these
      proteins may be used as a screening method for enteric GVHD. We studied
      prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that
      elevated fecal calprotectin levels were significantly associated with presence of
      GI-GVHD. We found a positive association between high F-calprotectin and severe
      gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1
      antitrypsin was independently associated with GI-GVHD. Testing for fecal
      calprotectin after allogeneic stem cell transplantation may be a useful screening
      tool. 

PMID- 25605404
TI  - Prevalence of tuberculosis and treatment outcome among university students in
      Northwest Ethiopia: a retrospective study.
AB  - BACKGROUND: Universities tend to be highly congregate settings, both in the
      classroom and in residences, and thus provide special opportunities for large
      number of persons to be exposed to a person with tuberculosis (TB). Despite the
      high prevalence of TB in Ethiopia, the TB prevalence and the treatment outcome
      among students have never been studied. Therefore, this study was aimed at
      determining the prevalence and treatment outcome of TB among students at
      University of Gondar from January 2007 to December 2011. METHODS: Data on age,
      sex, TB type, category, and treatment outcome of students with TB was collected
      from medical records of University of Gondar Hospital, TB Directly Observed
      Treatment Short Course (DOTS) clinic. All TB cases diagnosed with smear, culture,
      and/or radiography were included in the study. RESULTS: During the five year
      study period in the university, there were an average of 36 students with TB per
      year out of a mean of 10,036 enrolled students. Smear positive pulmonary TB,
      smear negative pulmonary TB, and extra pulmonary TB, respectively, were observed
      in 46 (25.4%), 81 (44.8%) and 54 (29.8%) of the cases. The prevalence of all
      forms of TB per 100,000 populations in the University ranged from 297.6 in 2009
      to 404 in 2011, respectively. The prevalence of TB in the Social Sciences and
      Humanities Faculty was higher than the one observed in the Medical College. The
      overall treatment outcome was classified as cured in 36 (19.9%), completed in 91
      (50.3%), defaulted in 9 (5%), failed in 3 (1.7%), died in 1 (0.6%), and
      transferred out in 41 (22.7%) of the cases. Treatment success rate (TSR) among
      students in University was generally low ranging from 58.1% in 2009 to 82.9% in
      2011 with a mean TSR of 70.2%. CONCLUSION: The prevalence of TB is higher in
      comparison to the national figure among students in University of Gondar. Active
      surveillance systems could be important to get a clear picture of the TB
      situation in such settings. Assessing the factors associated with the high
      prevalence to gear the TB control strategy could also be essential.

PMID- 25605405
TI  - End-to-patch anastomosis for microvascular transfer of free flaps with small
      pedicle.
AB  - BACKGROUND: Although perforator-to-perforator anastomosis in supermicrosurgery
      may be used in transferring free flaps with small vessels, it is still difficult
      in certain situations that include potentially infected wounds. Moreover, it is
      limited to smaller flaps. Anastomosis of large vessels is still safer for
      transfer of a large flap for most surgeons. The harvesting of a patch of the
      parent artery together with the perforator supplying the flap allows the surgeon
      to perform an anastomosis between the vessel ends of larger caliber, and possibly
      with greater anastomotic success. METHOD: When the vascular pedicle of a free
      flap is < 0.8 mm, an option is to take a cuff of the major artery for an end-to
      patch anastomosis. From 1983 to 2013, this method was applied to the anteromedial
      thigh (AMT) flap (seven cases), the groin flap (81 cases), and the free Becker's
      flap (five cases). When a patch was taken from the femoral artery, direct
      anastomosis for the major artery was performed using 5/0 Prolene sutures,
      followed by coverage with local soft tissue. When a patch was taken from the
      ulnar artery, a patch of vein graft was used for repair of the ulnar artery. In
      one case, a segment of the femoral artery was harvested with an AMT flap and a
      segment of a sartorius muscle flap; the compound tissue was transferred to the
      neck with the femoral artery to replace the left carotid artery. In the donor
      site, the defect of the femoral artery was reconstructed with an artificial
      graft. RESULTS: The flaps had no failure or partial necrosis, but one patient
      developed bleeding from the femoral artery 2 days postoperatively. It was treated
      by adding one more suture for the femoral artery and coverage with the sartorius
      muscle. In the ulnar artery, the patients did not complain of cold intolerance
      and the postoperative angiogram showed good patency of the ulnar artery after an
      average follow-up of 1 year. CONCLUSION: For the majority of plastic surgeons,
      this method provides a reliable and comfortable anastomosis when transferring a
      flap with small vessels. The only concern is to repair the donor artery carefully
      and ensure coverage of the repair site with local tissue.

PMID- 25605406
TI  - Easy access to the copper(III) anion [Cu(CF3 )4 ](-).
AB  - CuCl or pre-generated CuCF3 reacts with CF3 SiMe3 /KF in DMF in air to give
      [Cu(CF3 )4 ](-) quantitatively. [PPN](+) , [Me4 N](+) , [Bu4 N](+) , [PhCH2 NEt3
      ](+) , and [Ph4 P](+) salts of [Cu(CF3 )4 ](-) were prepared and isolated
      spectroscopically and analytically pure in 82-99% yield. X-ray structures of the
      [PPN](+) , [Me4 N](+) , [Bu4 N](+) , and [Ph4 P](+) salts were determined. A new
      synthetic strategy with [Cu(CF3 )4 ](-) was demonstrated, involving the removal
      of one CF3 (-) from the Cu atom in the presence of an incoming ligand. A novel
      Cu(III) complex [(bpy)Cu(CF3 )3 ] was thus prepared and fully characterized,
      including by single-crystal X-ray diffraction. The bpy complex is highly
      fluxional in solution, the barrier to degenerate isomerization being only 2.3
      kcal mol(-1) . An NPA study reveals a huge difference in the charge on the Cu
      atom in [Cu(CR3 )4 ](-) for R=F (+0.19) and R=H (+0.46), suggesting a higher
      electron density on Cu in the fluorinated complex.

PMID- 25605407
TI  - Distinct atmospheric patterns and associations with acute heat-induced mortality
      in five regions of England.
AB  - The main objective of this paper was to identify possible acute heat-induced
      summer mortality in five regions of England namely the Yorkshire and the Humber,
      West Midlands, North East, North West and South East regions and reveal
      associations with specific air flows. For this purpose, backward air mass
      trajectories corresponding to daily episodes of increased temperatures were
      produced and divided to clusters, in order to define atmospheric pathways
      associated with warm air mass intrusions. A statistically significant at 95 %
      confidence interval increase in daily total mortality (DTMORT) was observed
      during the selected episodes at all five regions and thus, heat-induced mortality
      was indicated. The calculated raise was more intense in the West Midlands, North
      West and South East regions, whereas the results in the North East and Yorkshire
      and the Humber regions were less evident. Large fractions of thermal episodes,
      elevated average temperature values and higher average DTMORT levels were
      primarily associated with the short-medium range South West (SW) and/or East
      South East (E-SE) trajectory clusters, suggesting relations among heat-induced
      mortality and specific atmospheric circulations. Short-medium length of SW and E
      SE airflows, calculated by an application of Haversine formula along the centroid
      trajectory of each cluster, implies the arrival of slow moving air masses.
      Atmospheric stagnation could enhance human thermal stress due to low wind speed.

PMID- 25605408
TI  - Health resort medicine in non-musculoskeletal disorders: is there evidence of its
      effectiveness?
AB  - Health resort medicine (HRM; in German: Kurortmedizin) is a field of medicine
      with long-lasting tradition in several European countries. A number of systematic
      reviews have shown the effectiveness of HRM in musculoskeletal conditions.
      Reviews focusing on the effectiveness of HRM in non-musculoskeletal disorders are
      rare. This systematic review aims to provide an overview about all types of
      health resort treatments applied in non-musculoskeletal conditions, to summarize
      evidence for its effectiveness and to assess the quality of published studies.
      MEDLINE, Web of Knowledge and Embase were searched for articles published between
      January 2002 and December 2013. We used a broad search strategy in order to find
      studies investigating the effects of HRM in non-musculoskeletal disorders. Two
      authors independently extracted data and assessed quality using the Effective
      Public Health Practice Project Quality Assessment Tool for Quantitative Studies
      (EPHPP-QAT). Forty-one studies (19 of them with control group) from eight
      countries examining the efficacy of various forms of spa treatment for 12 disease
      groups were included. The studies are markedly heterogeneous regarding study
      design, population and treatment. HRM treatment is associated with clinical
      improvement in diseases of the skin, respiratory, circulatory, digestive and
      nervous system among others. However, small samples, the lack of control groups
      and an insufficient follow-up often limit the generated evidence. The scientific
      literature of the last decade has shown that a number of non-musculoskeletal
      disorders are treated with different kinds of HRM. The challenge for the future
      will be to carry out thoroughly designed studies in larger patient populations to
      corroborate the impact of HRM treatment on non-musculoskeletal disorders.

PMID- 25605409
TI  - Clothing resultant thermal insulation determined on a movable thermal manikin.
      Part II: effects of wind and body movement on local insulation.
AB  - Part II of this two-part series study was focused on examining the effects of
      wind and body movement on local clothing thermal insulation. Seventeen clothing
      ensembles with different layers (i.e., 1, 2, or 3 layers) were selected for this
      study. Local thermal insulation with different air velocities (0.15, 1.55, and
      4.0 m/s) and walking speeds (0, 0.75, and 1.17 m/s) were investigated on a
      thermal manikin. Empirical equations for estimating local resultant clothing
      insulation as a function of local insulation, air velocity, and walking speed
      were developed. The results showed that the effects of wind and body movement on
      local resultant thermal resistance are complex and differ distinctively among
      different body parts. In general, the reductions of local insulation with wind at
      the chest, abdomen, and pelvis were greater than those at the lower leg and back,
      and the changes at the body extremity such as the forearm, thigh, and lower leg
      were higher than such immobile body parts as the chest and back. In addition, the
      wind effect interacted with the walking effect. This study may have important
      applications in human local thermal comfort modeling and functional clothing
      design.

PMID- 25605411
TI  - Severe cyanide poisoning from an alternative medicine treatment with amygdalin
      and apricot kernels in a 4-year-old child.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) is widespread
      in children with cancer and is poorly regulated. PATIENTS AND METHODS: Case
      report. RESULTS: We describe a case of severe cyanide poisoning arising from CAM
      use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial
      Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to
      our emergency department by ambulance services. Initial blood gas analysis
      demonstrated severe metabolic/lactic acidosis. On detailed questioning of the
      parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin)
      and oral apricot kernel was reported. After administering sodium thiosulfate,
      rapid improvement in his medical condition with complete recovery without need
      for further intensive care treatment was seen. Serum cyanide level was markedly
      elevated. CONCLUSIONS: Cyanide poisoning can be the cause of severe
      encephalopathy in children receiving CAM treatment with substances containing
      cyanogenic glycosides.

PMID- 25605412
TI  - PWD/PhJ mice have a genetically determined increase in nutrient-stimulated
      insulin secretion.
AB  - PWD/PhJ (PWD) is a wild-derived inbred mouse strain unrelated to commonly studied
      strains, such as C57BL/6J (B6). A chromosome substitution panel with PWD
      chromosomes transferred into the B6 background is commercially available and will
      facilitate genetic analysis of this strain. We have previously shown that the PWD
      strain is a model of primary fasting hyperinsulinemia. To identify more specific
      phenotypes affected by the genetic variation in PWD compared to B6 mice, we
      examined physiological mechanisms that may contribute to their elevated insulin
      levels. PWD mice had increased nutrient-stimulated insulin secretion due to
      factors inherent to their pancreatic islets. Insulin secretion responses to
      glucose, palmitate, and the metabolic intermediate alpha-ketoisocaproate were
      increased ~2-fold in islets from PWD mice compared to B6 islets. In contrast,
      there were no strain differences in processes affecting insulin secretion
      downstream of beta cell depolarization. PWD mice tended to have larger but fewer
      islets than B6 mice, resulting in similar insulin-staining areas and insulin
      content per unit of pancreatic tissue. However, pancreata of PWD mice were
      smaller, resulting in reduced total beta cell mass and pancreatic insulin content
      compared to B6 mice. Combined, these data suggest that the elevated fasting
      insulin levels in PWD mice result from increased generation of metabolic signals
      leading to beta cell depolarization and insulin secretion. Identification of the
      genetic differences underlying the enhanced nutrient-stimulated insulin secretion
      in this model may lead to new approaches to appropriately modulate insulin
      secretion for the treatment of obesity and type 2 diabetes. 

PMID- 25605414
TI  - Assessments of antibacterial and physico-mechanical properties for dental
      materials with chemically anchored quaternary ammonium moieties: thiol-ene
      methacrylate vs. conventional methacrylate system.
AB  - OBJECTIVE: Fabrication of low shrinkage stress and strain dental resins
      containing highly available immobilized bactericidal moieties has been reported.
      The goal of this study is producing dental restorative materials with long-last
      antibacterial activity and reduced secondary caries. It is anticipated that
      antibacterial properties of quaternary ammonium moieties chemically immobilized
      in the backbone of dental resins is directly depended on accessibility of these
      functions. In the present study the antibacterial effect of a series of
      antibacterial monomers polymerized in a ternary thiol-ene-methacrylate system
      were compared with corresponding classical methacrylate system against
      Streptococcus mutans (an oral bacteria Strain). Physical and mechanical
      properties of dental materials obtained from these two systems were also
      evaluated and compared. METHODS: The viscosities of the resin matrixes were
      measured on a MCR 300 rheometer. Degree of conversion (DC%) of monomers was
      measured using FTIR spectroscopy. The shrinkage-strain of photocured resins was
      measured using the bonded-disk technique. A universal testing machine combined
      with a stress measurement device was utilized to measure the polymerization
      induced shrinkage stress. Viscoelastic properties of the samples were also
      determined by dynamic mechanical thermal analysis (DMTA). Assessment of
      antibacterial properties was performed through agar diffusion test (AD) to
      confirm non-release behavior of chemically anchored moieties. Quantitative assay
      of antibacterial activity was evaluated through direct contact test (DCT) against
      S. mutans. Direct contact cytotoxicity assay with fibroblast cell line L-929 was
      also performed to find more insight regarding cytotoxicity of the antibacterial
      matrixes. The data were analyzed and compared by ANOVA and Tukey HSD tests
      (significance level=0.05). RESULTS: Neat methacrylate systems had significantly
      higher viscosity than thiol-ene-methacrylate analogous. The degree of conversion
      of methacrylate moieties in thiol-ene-methacrylate system was improved in
      comparison to conventional methacrylate system. Shrinkage stress and strain of
      thiol-ene-methacrylate system was lower than the neat methacrylate system. The
      thiol-ene-methacrylate systems show increased homogeneity and decreased glass
      transition temperature (Tg) and crosslink density (nuc) in comparison to the neat
      methacrylate-based resins. The incorporated monofuctional quaternized monomer
      reduces degree of conversion, shrinkage stress and crosslink density of matrix.
      The results showed significant improvement in antibacterial activity and
      cytocompatibility of dental materials obtained from thiol-ene polymerization
      system. SIGNIFICANCE: It was shown that with proper control of monomers molar
      ratio, significant improvement in antibacterial activity and cytocompatibility as
      well as acceptable mechanical properties can be attained for dental resins
      prepared through the application of thiol-ene polymerization methodology.

PMID- 25605413
TI  - Evaluating a standardised tool to explore the nature and extent of foot and ankle
      injuries in amateur and semi-professional footballers.
AB  - BACKGROUND: Most studies of football injuries include professional players and
      data have been collected in without a single validated, standardised tool. We
      aimed to develop a new standardised questionnaire for assessing injuries among
      non-professional footballers and pilot its use. METHOD: A questionnaire was
      developed using input from footballers, healthcare professionals and
      triangulation from the literature. The new tool was piloted among players
      representing amateurs and semi-professionals. Their comments were used
      iteratively to improve the instrument. RESULTS: The development phase produced a
      33-item questionnaire collecting quantitative and qualitative data. In the pilot
      phase, 42 questionnaires were distributed, 34 (81%) returned. Respondents
      reported total of 273 football-related injuries, 114 affecting the foot/ankle (70
      at the ankle and 44 at the foot). In total, 44% of respondents had suffered one
      or more foot/ankle injuries in the past 12 months. CONCLUSION: We developed a new
      standardised tool which we found to be well-completed by young male footballers
      in semi-professional and amateur settings with an excellent response rate. Our
      results suggested that foot/ankle injuries were common, larger studies in non
      professionals are needed to identify risk factors for injury and develop
      pragmatic advice for prevention.

PMID- 25605415
TI  - Possible relation between olfaction and anxiety in healthy subjects.
AB  - AIMS: While olfaction is a sense closely associated with the limbic system and
      emotions, the relation between emotional status and olfactory functioning has not
      been well documented. This study aimed to examine the possible effect of anxiety
      on olfaction in healthy subjects. METHODS: We investigated the effect of state
      and trait anxiety on the detection and recognition thresholds for five different
      odors in 124 healthy subjects (62 men and 62 women, mean age = 27.2 years) using
      a T&T olfactometer. RESULTS: While the influences of age, socioeconomic status,
      IQ, and smoking history on olfaction were not significant, women had a lower
      recognition threshold for the odor of sweet fruit and a higher detection
      threshold for that of rotten food as compared with men. Both state and trait
      anxiety ratings were significantly associated with reduced olfactory ability,
      especially for identification of rose odor. CONCLUSIONS: These findings suggest
      that emotional status affects olfactory functioning in healthy subjects. Our
      findings may also partly explain the mild olfactory impairment reported in
      clinical conditions, such as anxiety disorders.

PMID- 25605410
TI  - Deubiquitinases and the new therapeutic opportunities offered to cancer.
AB  - Deubiquitinases (DUBs) play important roles and therefore are potential drug
      targets in various diseases including cancer and neurodegeneration. In this
      review, we recapitulate structure-function studies of the most studied DUBs
      including USP7, USP22, CYLD, UCHL1, BAP1, A20, as well as ataxin 3 and connect
      them to regulatory mechanisms and their growing protein interaction networks. We
      then describe DUBs that have been associated with endocrine carcinogenesis with a
      focus on prostate, ovarian, and thyroid cancer, pheochromocytoma, and
      adrenocortical carcinoma. The goal is enhancing our understanding of the
      connection between dysregulated DUBs and cancer to permit the design of
      therapeutics and to establish biomarkers that could be used in diagnosis and
      prognosis. 

PMID- 25605417
TI  - A case of splenic rupture within an umbilical hernia with loss of domain.
AB  - INTRODUCTION: Massive ventral hernia with loss of abdominal domain is a
      particularly complex disease. We present a case of a massive umbilical hernia
      with loss of abdominal domain containing the small bowel, colon, and spleen that
      presented with spontaneous splenic rupture. CASE REPORT: The patient was an 82
      year-old Caucasian female with multiple comorbidities, on anti-coagulation for
      cardiac dysrhythmia with a congenital umbilical hernia with loss of abdominal
      domain which had progressed over multiple years. She presented to an outside
      hospital with history of a left-sided abdominal pain accompanying fatigue and
      weakness.A CT scan of the abdomen revealed an umbilical hernia with loss of
      abdominal domain containing the patient's entire small bowel, colon, pancreas,
      and the spleen. The spleen had ruptured with associated hemorrhage and hematoma
      in the hernia sac.Management included a multidisciplinary approach with
      particular attention to comorbidities and hemodynamic monitoring due to splenic
      rupture. Given the need for lifetime anticoagulation, a splenectomy was planned
      along with simultaneous abdominal wall reconstruction. The patient underwent an
      exploratory laparotomy, splenectomy, bilateral posterior component separation
      with transversus abdominis release, and a retrorectus/preperitoneal placement of
      heavy weight polypropylene mesh.During the postoperative period, the patient
      remained intubated initially due to elevated airway pressures before transferring
      to the regular nursing floor. The remainder of the patient's hospital stay was
      complicated by a postoperative ileus requiring nasogastric tube decompression and
      a DVT and PE necessitating anticoagulation. The ileus eventually resolved and
      diet was slowly advanced. The patient was discharged on POD17. DISCUSSION: To our
      knowledge, this is the first report in the literature describing a splenic
      rupture that occurred within the hernia sac of a congenital umbilical hernia.
      This report serves to highlight that even with novel cases of massive and
      atypical hernias, posterior component separation with transversus abdominis
      release is a reproducible repair that can be performed with good result in a
      variety of circumstances.

PMID- 25605418
TI  - Artificial neural network in diagnosis of urothelial cell carcinoma in urine
      cytology.
AB  - AIMS AND OBJECTIVE: To build up an artificial neural network (ANN) model in the
      diagnosis of urothelial cell carcinoma (UCC) in urine cytology smears. MATERIAL
      AND METHODS: We randomly selected a total of 115 urine cytology samples, out of
      which 59 were histopathology proven UCC cases and remaining 56 were benign cases
      from routine cytology samples. All the carcinoma cases were proven on
      histopathology. Image morphometric analysis was performed on Papanicolaou's
      stained smears to study nuclear area, diameter, perimeter, standard deviation of
      nuclear area, and integrated gray density. Detailed cytological features were
      also studied in each case by two independent observers and were semi
      quantitatively graded. The back propagation ANN model was designed as 17-11-3
      with the help of heuristic search. The cases were randomly partitioned as
      training, validation, and testing sets by the program. There were 79 cases for
      training set, 18 cases for validation set and 18 cases for test set. RESULT: In
      the training set, ANN was able to diagnose all the malignant and benign cases. In
      the test set, all the benign and malignant cases were diagnosed correctly.
      However, one of the low grade cases was diagnosed as high grade UCC by ANN model.
      CONCLUSIONS: We successfully built an ANN model in urine from the visual and
      morphometric data to identify the benign and malignant cases. In addition, the
      system can also identify the low grade and high grade UCC cases.

PMID- 25605416
TI  - Perioperative blood transfusion as a poor prognostic factor after aggressive
      surgical resection for hilar cholangiocarcinoma.
AB  - BACKGROUND: Blood transfusion is linked to a negative outcome for malignant
      tumors. The aim of this study was to evaluate aggressive surgical resection for
      hilar cholangiocarcinoma (HCCA) and assess the impact of perioperative blood
      transfusion on long-term survival. METHODS: Sixty-six consecutive major
      hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile
      duct for HCCA were performed using macroscopically curative resection at our
      institute from 2002 to 2012. Clinicopathologic factors for recurrence and
      survival were retrospectively assessed. RESULTS: Overall survival rates at 1, 3,
      and 5 years were 86.7, 47.3, and 35.7 %, respectively. In univariate analysis,
      perioperative blood transfusion and a histological positive margin were two of
      several variables found to be significant prognostic factors for recurrence or
      survival (P<0.05). In multivariate analysis, only perioperative blood transfusion
      was independently associated with recurrence (hazard ratio (HR)=2.839 (95 %
      confidence interval (CI), 1.370-5.884), P=0.005), while perioperative blood
      transfusion (HR=3.383 (95 % CI, 1.499-7.637), P=0.003) and R1 resection (HR=3.125
      (95 % CI, 1.025-9.530), P=0.045) were independent risk factors for poor survival.
      CONCLUSIONS: Perioperative blood transfusion is a strong predictor of poor
      survival after radical hepatectomy for HCCA. We suggest that circumvention of
      perioperative blood transfusion can play an important role in long-term survival
      for patients with HCCA.

PMID- 25605419
TI  - 17beta-estradiol attenuates homocysteine-induced oxidative stress and
      inflammatory response as well as MAPKs cascade via activating PI3-K/Akt signal
      transduction pathway in Raw 264.7 cells.
AB  - Oxidative stress, inflammatory response, and mitogen-activated protein kinases
      (MAPKs) cascade are significant pathogenic factors of osteoporosis. It has been
      reported that elevated homocysteine (Hcy) may activate oxidative stress and
      reduce bone mineral density in post-menopausal osteoporosis. Moreover, hormone
      replacement therapy has been widely used in clinic to prevent and treat post
      menopausal women with osteoporosis and osteoporotic fracture, but the molecular
      mechanisms and relevant signal transduction pathways underlying the action of Hcy
      remain unclear. In this study, we investigated the effects of 17beta-estradiol
      (17beta-E2) on the Hcy-induced oxidative stress, inflammatory response and MAPKs
      cascade, as well as the underlying signal transduction pathway in murine Raw
      264.7 cells. The reactive oxygen species (ROS) was assessed by
      fluorospectrophotometry. The proinflammatory cytokines tumor necrosis factor
      alpha (TNF-alpha) and interleukin (IL)-1beta were analyzed by double
      immunofluorescence labeling and reverse transcriptase polymerase chain reaction
      assay, respectively. Furthermore, phosphorylation levels of MAPKs cascade were
      measured by western blot analysis. A specific phosphatidylinositol 3-kinase (PI3
      K) inhibitor, Wortmannin (1 MUM) was employed to determine whether PI3-K/Akt
      signaling pathway mediated the 17beta-E2's effect on Raw 264.7 cells. 17beta-E2
      markedly decreased the ROS production induced by Hcy, the expression of TNF-alpha
      and IL-1beta at protein and mRNA levels, and down-regulated the phosphorylation
      of MAPKs (ERK1/2, JNK and p38). These suppressing effects of 17beta-E2 on Hcy
      induced changes were reversed by pretreatment with PI3-K inhibitor Wortmannin.
      The results indicate that 17beta-estradiol may attenuate Hcy-induced oxidative
      stress, inflammatory response and up-regulation of MAPKs in Raw 264.7 cells via
      PI3-K/Akt signal transduction pathway. 

PMID- 25605420
TI  - Activation of mTOR signaling pathway is secondary to neuronal excitability in a
      mouse model of mesio-temporal lobe epilepsy.
AB  - Recent studies in animal models have suggested that the mammalian target of
      rapamycin (mTOR) signaling pathway is involved in several features of mesio
      temporal lobe epilepsy (MTLE), and that its inhibition could have therapeutic
      interests. However, it remains controversial whether mTOR activation is the cause
      or the consequence of MTLE. We previously showed in a mouse model of MTLE
      associated with hippocampal sclerosis that increased neuronal excitability and
      brain-derived neurotrophic factor (BDNF) overexpression contribute to the
      development of morphological features of this form of epilepsy. Here, we
      addressed whether mTOR activation promotes MTLE epileptogenesis via increasing
      neuronal excitability and/or BDNF expression or rather mediates neuroplasticity
      associated with hippocampal sclerosis. In mice injected intrahippocampally with
      kainate (1 nmol), we showed a biphasic increase of phospho-S6 (p-S6) ribosomal
      protein expression, the downstream product of the mTOR signaling pathway, in the
      dispersed granule cell layer (GCL) of the dentate gyrus with a second phase
      lasting up to 6 months. Chronic treatment with rapamycin suppressed p-S6
      expression, granule cell dispersion and mossy fiber sprouting, but did not reduce
      cell loss, BDNF overexpression, glutamic acid decarboxylase (GAD)67 expression or
      the development of hippocampal paroxysmal discharges. Neuronal inhibition by
      midazolam (2 * 10 mg/kg, i.p.) abolished the increased expression of p-S6 in the
      dispersed GCL. Our data suggest that activation of the mTOR signaling pathway
      results from the increased neuronal excitation that develops in the GCL and may
      contribute to MTLE morphological changes. However, these data do not support the
      role of this pathway in the development of MTLE or its inhibition as a therapy
      for this form of epilepsy.

PMID- 25605421
TI  - Northernmost record of the little gulper shark Centrophorus uyato in the north
      eastern Atlantic Ocean, with taxonomical notes on Centrophorus zeehaani.
AB  - A specimen of the little gulper shark Centrophorus uyato was collected in the
      Norwegian Sea off the coast of northern Norway, marking the northernmost record
      of the species in the eastern North Atlantic Ocean. Morphological characteristics
      collected from the specimen indicate a close relationship to the Australian
      species Centrophorus zeehaani. DNA barcoding analysis of the mitochondrial
      cytochrome oxidase subunit I (coI) gene for species of Centrophorus suggests
      conspecificity of C. uyato and C. zeehaani.

PMID- 25605422
TI  - Enhanced xyloglucan-specific endo-beta-1,4-glucanase efficiency in an engineered
      CBM44-XegA chimera.
AB  - Xyloglucan-specific endo-beta-1,4-glucanases (Xegs, EC 3.2.1.151) exhibit high
      catalytic specificity for beta-1,4 linkages of xyloglucan, a branched
      hemicellulosic polysaccharide abundant in dicot primary cell walls and present in
      many monocot species. In nature, GH12 Xegs are not associated with carbohydrate
      binding modules (CBMs), and here, we have investigated the effect of the fusion
      of the xyloglucan-specific CBM44 on the structure and function of a GH12 Xeg from
      Aspergillus niveus (XegA). This fusion presented enhanced catalytic properties
      and conferred superior thermal stability on the XegA. An increased k cat
      (chimera, 177.03 s(-1); XegA, 144.31 s(-1)) and reduced KM (chimera, 1.30 mg mL(
      1); XegA, 1.50 mg mL(-1)) resulted in a 1.3-fold increase in catalytic efficiency
      of the chimera over the parental XegA. Although both parental and chimeric
      enzymes presented catalytic optima at pH 5.5 and 60  degrees C, the
      thermostabilitiy of the chimera at 60  degrees C was greater than the parental
      XegA. Moreover, the crystallographic structure of XegA together with small-angle
      X-ray scattering (SAXS) and molecular dynamics simulations revealed that the
      spatial arrangement of the domains in the chimeric enzyme resulted in the
      formation of an extended binding cleft that may explain the improved kinetic
      properties of the CBM44-XegA chimera.

PMID- 25605423
TI  - Impact of elevated CO2 and N addition on bacteria, fungi, and archaea in a marsh
      ecosystem with various types of plants.
AB  - The individual effects of either elevated CO2 or N deposition on soil microbial
      communities have been widely studied, but limited information is available
      regarding the responses of the bacteria, fungi, and archaea communities to both
      elevated CO2 and N in wetland ecosystems with different types of plants. Using a
      terminal restriction fragment length polymorphism (T-RFLP) analysis and real-time
      quantitative PCR (RT-Q-PCR), we compared communities of bacteria, fungi, and
      archaea in a marsh microcosm with one of seven macrophytes, Typha latifolia,
      Phragmites japonica, Miscanthus sacchariflorus, Scirpus lacustris, Juncus
      effusus, Phragmites australis, or Zizania latifolia, after exposing them to eCO2
      and/or amended N for 110 days. Overall, our results showed that the elevated CO2
      and N may affect the bacterial and archaeal communities, while they may not
      affect the fungal community in terms of both diversity and abundance. The effects
      of elevated CO2 and N on microbial community vary depending on the plant types,
      and each microbial community shows different responses to the elevated CO2 and N.
      In particular, elevated CO2 might force a shift in the archaeal community
      irrespective of the plant type, and the effect of elevated CO2 was enhanced when
      combined with the N effect. This study indicates that elevated CO2 and N addition
      could lead to changes in the community structures of bacteria and archaea. Our
      results also suggest that the fungal group is less sensitive to external changes,
      while the bacterial and archaeal groups are more sensitive to them. Finally, the
      characteristics of the plant type and relevant physicochemical factors induced by
      the elevated CO2 and N may be important key factors structuring the microbial
      community's response to environmental change, which implies the need for a more
      comprehensive approach to understanding the pattern of the wetland response to
      climate change.

PMID- 25605424
TI  - Outcomes of regenerative treatment with rhPDGF-BB and rhFGF-2 for periodontal
      intra-bony defects: a systematic review and meta-analysis.
AB  - BACKGROUND: The aim was to evaluate the effects of recombinant human platelet
      derived growth factor-BB (rhPDGF-BB) and recombinant human fibroblast growth
      factor-2 (rhFGF-2) on treating periodontal intra-bony defects, compared to the
      control (carrier alone). METHODS: Electronic and hand searches were performed to
      identify eligible studies. The weighed mean differences of linear defect fill
      (LDF), probing depth (PD) reduction, clinical attachment level (CAL) gain and
      gingival recession (GR) were calculated using random effect meta-analysis.
      RESULTS: The searches yielded 1018 articles, of which seven studies were
      included. Only one included study was considered at low risk of bias. The
      outcomes that reached statistical significance in comparison to carriers alone
      included: LDF (0.95 mm, 95% CI: 0.62-1.28 mm or 20.17%, 95% CI: 11.81-28.54%) and
      CAL gain (0.34 mm, 95% CI: 0.03-0.65 mm) for PDGF, and LDF (21.22%, 95% CI: 5.82
      36.61%) for FGF-2. CONCLUSIONS: Within the limits of this review, rhPDGF-BB
      demonstrated significantly more LDF and CAL gain; rhFGF-2 resulted in
      significantly higher percentage of LDF.

PMID- 25605426
TI  - Synthesis and characterization of antibacterial carboxymethylcellulose/CuO bio
      nanocomposite hydrogels.
AB  - In this study, carboxymethyl cellulose/CuO nanocomposite hydrogels have been
      synthesized through the in situ formation of CuO nanoparticles within swollen
      carboxymethyl cellulose hydrogels. The aim of the study was to investigate
      whether these hydrogels have the potential to be used in antibacterial
      applications. The formation of CuO nanoparticles in the hydrogels was confirmed
      using X-ray diffraction and scanning electron microscopy studies. In addition,
      swelling behavior of nanocomposite hydrogels was investigated in various pH
      values and salt solutions. Furthermore, the CuO nanocomposite hydrogels were
      tested for antibacterial activities. The antibacterial activity of the
      nanocomposite hydrogels was studied by inhibition zone method against Escherichia
      coli and Staphylococcus aureus. The nanocomposite hydrogels demonstrated
      excellent antibacterial effects. Therefore, the developed carboxymethyl
      cellulose/CuO nanocomposite hydrogels can be used effectively for biomedical
      application. 

PMID- 25605425
TI  - Nonsurgical treatment of peri-implantitis using an air-abrasive device or
      mechanical debridement and local application of chlorhexidine. Twelve-month
      follow-up of a prospective, randomized, controlled clinical study.
AB  - OBJECTIVES: The purpose of this prospective, parallel group-designed, randomized
      controlled clinical study was the evaluation of the effectiveness of an air
      abrasive device (AAD) for nonsurgical treatment of peri-implantitis. MATERIAL AND
      METHODS: Twenty five patients, showing at least one implant with initial to
      moderate peri-implantitis, underwent an oral hygiene programme and were randomly
      treated using either (1) AAD (amino acid glycine powder) or (2) mechanical
      debridement using carbon curettes and antiseptic therapy with chlorhexidine
      digluconate (mechanical debridement (MDA)). Clinical parameters were measured at
      baseline and 12 months after treatment (e.g. bleeding on probing (BOP), probing
      depth (PD), clinical attachment level (CAL)). RESULTS: At 12 months, the AAD
      group revealed significantly higher (p < 0.05; unpaired t test) decrease in mean
      BOP scores when compared with MDA-treated sites (41.2 +/- 29.5 vs. 16.6 +/-
      33.4%). Both groups exhibited comparable PD reductions (AAD = 0.5 +/- 0.9 mm vs.
      MDA = 0.4 +/- 0.9 mm) and CAL gains (AAD = 0.6 +/- 1.3 mm vs. MDA = 0.5 +/- 1.1
      mm) (p > 0.05; Mann-Whitney test, respectively). CONCLUSIONS: Within its
      limitations, the present study has indicated that both treatment procedures
      resulted in comparable but limited CAL gains at 12 months. Furthermore, it could
      be detected that AAD was associated with significantly higher BOP decrease than
      MDA. CLINICAL RELEVANCE: The present results have indicated that nonsurgical
      therapy of peri-implantitis using both AAD and MDA resulted in comparable PD
      reductions and CAL gains after 12 months of healing. The BOP reductions were
      significantly higher in the AAD in comparison to the MDA group. So, AAD may be
      more effective for nonsurgical therapy of peri-implantitis than MDA.

PMID- 25605427
TI  - Graphite sulphate - a precursor to graphene.
AB  - Graphite sulphate is used as a precursor to graphene for the first time. The
      positively charged graphene layers react with water to yield a processable
      graphene derivative. The unprecedented low density of defects is determined to be
      0.06% on average and may open the way for electronic applications. 

PMID- 25605428
TI  - Statistical analysis of molecule colocalization in bioimaging.
AB  - The quantitative analysis of molecule interactions in bioimaging is key for
      understanding the molecular orchestration of cellular processes and is generally
      achieved through the study of the spatial colocalization between the different
      populations of molecules. Colocalization methods are traditionally divided into
      pixel-based methods that measure global correlation coefficients from the overlap
      between pixel intensities in different color channels, and object-based methods
      that first segment molecule spots and then analyze their spatial distributions
      with second-order statistics. Here, we present a review of such colocalization
      methods and give a quantitative comparison of their relative merits in different
      types of biological applications and contexts. We show on synthetic and
      biological images that object-based methods are more robust statistically than
      pixel-based methods, and allow moreover to quantify accurately the number of
      colocalized molecules.

PMID- 25605429
TI  - miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty
      liver disease by targeting HMGCR.
AB  - Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue
      with a prevalence of 15-30% in Western populations and 6-25% in Asian
      populations. Certain studies have revealed the alteration of microRNA (miRNA or
      miR) profiles in NAFLD and it has been suggested that miR-21 is associated with
      NAFLD. In the present study, we measured the serum levels of miR-21 in patients
      with NAFLD and also performed in vitro experiments using a cellular model of
      NAFLD to further investigate the effects of miR-21 on triglyceride and
      cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts
      its effects on NAFLD was identified. The results revealed that the serum levels
      of miR-21 were lower in patients with NAFLD compared with the healthy controls.
      In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression
      was increased in the serum of patients with NAFLD both at the mRNA and protein
      level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with
      palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in
      the in vivo experiments, the expression levels of miR-21 were decreased and those
      of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay
      revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an
      effect on both HMGCR transcript degradation and protein translation. Furthermore,
      the results from the in vitro experiments revealed that miR-21 decreased the
      levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in
      the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR
      overexpression. Taken together, to the best of our knowledge, the present study
      is the first to report that miR-21 regulates triglyceride and cholesterol
      metabolism in an in vitro model of NAFLD, and that this effect is achieved by the
      inhibition of HMGCR expression. We speculate that miR-21 may be a useful
      biomarker for the diagnosis and treatment of NAFLD.

PMID- 25605430
TI  - Making the Blue Zones: Neoliberalism and nudges in public health promotion.
AB  - This paper evaluates the ideological and political origins of a place-based and
      commercial health promotion effort, the Blue Zones Project (BZP), launched in
      Iowa in 2011. Through critical discourse analysis, I argue that the BZP does
      reflect a neoliberalization of public health, but as an "actually existing
      neoliberalism" it emerges from a specific policy context, including dramatic
      health sector policy changes due to the national Affordable Care Act, also known
      as Obamacare; a media discourse of health crisis for an aging Midwestern
      population; and an effort to refashion Iowa cities as sites of healthy and active
      living, to retain and attract a creative class of young entrepreneurs. The BZP
      employs many well-known mechanisms of neoliberal governance: the public-private
      partnership; competition among communities for "public" funds; promotion of an
      apolitical discourse on individual responsibility and ownership of health;
      decentralizing governance to the "community" level; and marketing, branding, and
      corporate sponsorship of public projects. The BZP exemplifies the process of
      "neoliberal governmentality," by which individuals learn to govern themselves and
      their "life projects" in line with a market-based rationality. However, with its
      emphasis on "nudging" individuals towards healthy behaviors through small changes
      in the local environment, the BZP reflects the rise of "libertarian paternalism,"
      a variant of neoliberalism, as a dominant ideology underlying contemporary health
      promotion efforts. 

PMID- 25605431
TI  - Clarity, constructive debate and progress in developing methodological and
      conceptual frameworks for understanding pharmaceuticalization: a reply to
      Abraham.

PMID- 25605432
TI  - A new myrsinol-type diterpene polyester from Euphorbia dracunculoides Lam.
AB  - A new myrsinol-type diterpene polyester, 14-deoxo-3beta-O-propinoyl
      2alpha,5alpha,7beta,15beta-tetra-O-acetyl-14alpha-O-benzoyl-myrsinol (1), and its
      known analogue, 14-deoxo-3beta-O-prorionyl-5alpha,15beta-di-O-acetyl-7beta-O
      nicotinoyl-myrsinol-14beta-acetate (2), together with a monoterpenoid,
      pubinernoid A (3), two indole alkaloids, neoechinulin A (4) and
      dihydroxyisoechinulin A (5), two benzene derivatives, siringin (6) and (3
      methoxyphenyl) acetic acid (7), were isolated from the 70% acetone extract of the
      aerial parts of Euphorbia dracunculoides Lam. Their structures were elucidated on
      the basis of spectroscopic evidence and comparison with literature reports. The
      absolute configuration of 1 was deduced by comparing experimental and calculated
      ECD spectra. Among them, compounds 4 and 5 were first obtained from the plant
      source. In addition, the (13)C NMR data of compound 2 was reported for the first
      time. 

PMID- 25605434
TI  - An international survey of patients with cervical dystonia.
AB  - This was an international survey undertaken to assess cervical dystonia (CD)
      patients own perceptions of their illness and its management. A total of 1,071
      self-identified respondents with CD in 38 countries completed the online survey
      between March and December 2012. The mean time since diagnosis was 9.6 years and
      over half (54%) of patients surveyed were not diagnosed in the first year. When
      asked how the symptoms of CD affected them, two-thirds (66%) of patients reported
      they experienced a lot of pain, and 61% said that they suffered depression and
      mood alterations; only 7% reported no impact on their lives. Despite problems
      with the diagnosis, almost 70% of respondents reported being satisfied with the
      overall relationship with their doctor. Patient treatment expectations were high,
      with 63% expecting freedom from spasms and 62% expecting freedom from pain. Over
      half (53%) expected to be able to return to a normal routine (53%). The most
      common treatment reported was botulinum toxin (BoNT) (86%), followed by oral
      medication (58%) and physiotherapy/physical therapy (37%). Among patients treated
      on BoNT, 56% were fairly/very satisfied, 25% were fairly/very dissatisfied and
      20% were neither satisfied nor dissatisfied with the outcome. In conclusion, this
      international survey highlights the broad impact of CD on several aspects of
      patient life. Taken overall, the survey suggests that that patients need to be
      better informed about their condition, treatments available and the limitations
      of those treatments. It may be that realistically managing patient expectations
      of treatment would reduce the dissatisfaction of some patients.

PMID- 25605436
TI  - Natalizumab in MS: JC antibody index.

PMID- 25605435
TI  - Multiple sclerosis in Japan appears to be a milder disease compared to the UK.
AB  - Multiple sclerosis (MS) is relatively common in the West, but rare in Japan. In
      the literature, there are few comparative data regarding disease severity
      throughout the world. The objective of this study was to compare disability in
      patients from a UK and a Japanese MS cohort. We retrospectively analysed the
      clinical features of patients with MS from a UK and Japanese MS centre. The
      Multiple Sclerosis Severity Score (MSSS), which adjusts the Expanded Disability
      Status Scale score according to disease duration, was used as a marker of disease
      severity. One thousand one hundred forty-eight UK patients and 104 Japanese
      patient were identified representing the relative national prevalence.
      Demographics and disease duration did not differ between the groups. Median MSSS
      was significantly different between the two groups (Japan 3.34 vs. UK 5.87, p <
      0.001). Primary progressive MS was more common in the UK (12.9%) than in the
      Japanese cohort (3%, p = 0.044). The majority of Japanese patients (83.7% vs. UK
      17%) had been exposed to disease modifying treatments (DMTs). Exposure to DMTs
      did not show a significant effect on disability. In conclusion, this study
      suggests that MS in Japan may be associated with less disability than in UK. More
      Japanese patients were treated with DMTs. Differences in treatments do not seem
      to explain the disparity in disability severity. This suggests either genetic or
      environmental influences on disease severity.

PMID- 25605437
TI  - PET-Florbetapir findings in primary cerebral amyloidoma.

PMID- 25605438
TI  - Differences in methylphenidate abuse rates among methadone maintenance treatment
      patients in two clinics.
AB  - Methylphenidate, an amphetamine-like prescription medication for attention
      deficit hyperactivity disorder (ADHD) was suspected as being abused among
      methadone maintenance treatment (MMT) patients. We tested its presence in the
      routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT
      clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating
      Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR
      psychiatric diagnosis from admission were retrieved, and retention following 6
      months. None of the 190 patients in Las Vegas tested positive for
      methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated
      (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05),
      and a higher benzodiazepine (BDZ) abuse rate (p < 0.0005), with no difference in
      age, gender, duration in MMT, cannabis, opiates, and cocaine abuse and infectious
      disease. Of the methylphenidate abuse 42.2% have take-home methadone dose
      privileges. Not like opiate use, being methylphenidate positive did not relate to
      6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated,
      with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among
      ADHD subjects might indicate their using it as self-medication, raising a
      possible indication for its prescription for that subgroup of MMT patients. The
      high rate of methylphenidate abuse in Israel needs future study.

PMID- 25605439
TI  - Interaction between VWF and FVIII in treating VWD.
AB  - In patients with von Willebrand disease (VWD), the absence of von Willebrand
      factor (VWF) antigen leads to the premature loss of endogenous circulating
      secreted factor VIII (FVIII), thereby resulting in the dual defect in
      haemostasis. Consequently, correcting the VWF deficiency also acts to correct the
      associated defect in FVIII activity because exogenous VWF forms complexes with
      and protects endogenous FVIII. The purpose of this study was to summarise
      relevant aspects of the interaction between VWF and FVIII and to analyse their
      effects on VWD treatment. Differences in the VWF/FVIII ratios in coagulation
      factor concentrates should be considered when treating VWD. 

PMID- 25605440
TI  - Nitric oxide selectively suppresses IH currents mediated by HCN1-containing
      channels.
AB  - Hyperpolarization-activated non-specific cation-permeable channels (HCN) mediate
      I(H) currents, which are modulated by cGMP and cAMP and by nitric oxide (NO)
      signalling. Channel properties depend upon subunit composition (HCN1-4 and
      accessory subunits) as demonstrated in expression systems, but physiological
      relevance requires investigation in native neurons with intact intracellular
      signalling. Here we use the superior olivary complex (SOC), which exhibits a
      distinctive pattern of HCN1 and HCN2 expression, to investigate NO modulation of
      the respective I(H) currents, and compare properties in wild-type and HCN1
      knockout mice. The medial nucleus of the trapezoid body (MNTB) expresses HCN2
      subunits exclusively, and sends inhibitory projections to the medial and lateral
      superior olives (MSO, LSO) and the superior paraolivary nucleus (SPN). In
      contrast to the MNTB, these target nuclei possess an I(H) with fast kinetics, and
      they express HCN1 subunits. NO is generated in the SOC following synaptic
      activity and here we show that NO selectively suppresses HCN1, while enhancing IH
      mediated by HCN2 subunits. NO hyperpolarizes the half-activation of HCN1-mediated
      currents and slows the kinetics of native IH currents in the MSO, LSO and SPN.
      This modulation was independent of cGMP and absent in transgenic mice lacking
      HCN1. Independently, NO signalling depolarizes the half-activation of HCN2
      mediated I(H) currents in a cGMP-dependent manner. Thus, NO selectively
      suppresses fast HCN1-mediated I(H) and facilitates a slow HCN2-mediated I(H) , so
      generating a spectrum of modulation, dependent on the local expression of HCN1
      and/or HCN2.

PMID- 25605441
TI  - Fast doping of Cu into ZnSe NCs by hydrazine promoted cation exchange in aqueous
      solution at room temperature.
AB  - Controllable doping is an effective way of tuning the properties of semiconductor
      nanocrystals (NCs). In this work, a simple strategy of fast doping Cu ions into
      ZnSe NCs under ambient conditions was proposed. The principle of doping is based
      on hydrazine (N2H4) promoted cation exchange reaction. By direct addition of Cu
      ion stock solution into the preformed ZnSe NCs, Cu doped ZnSe NCs can be
      obtained. Furthermore, the emission of doped NCs can be tuned by changing the
      amount of impurity ion addition. The cation exchange reaction is facilitated by
      three factors: 1) N2H4 addition, 2) fast impurity ions, and 3) partial stabilizer
      removal. The proposed cation exchange reaction in aqueous solution could be an
      alternate route for NC doping as well as synthesis of ionic NCs. 

PMID- 25605442
TI  - Cytotoxic activity and protein binding through an unusual oxidative mechanism by
      an iridium(I)-NHC complex.
AB  - A new NHC iridium(I) complex (1) showing significant antiproliferative properties
      in vitro is described here. Its crystal structure, solution behaviour and
      interactions with the model proteins cytochrome c (cyt c) and lysozyme were
      investigated. High resolution ESI-MS measurements suggest that this iridium(i)
      complex acts as a prodrug and binds cyt c tightly through an unusual "oxidative"
      mechanism. Eventually, an iridium(III)-NHC fragment is found associated to the
      protein.

PMID- 25605443
TI  - Effects of mesenchymal stem cells in renovascular hypertension.
AB  - NEW FINDINGS: What is the topic of this review? The major topic of this review
      addresses the effects of mesenchymal stem cell treatment in renovascular
      hypertension. What advances does it highlight? This therapy may be a promising
      strategy to treat renovascular hypertension and its renal consequences in the
      near future. Renovascular hypertension induced by the two-kidney, one-clip
      technique is a renin-angiotensin system-dependent model that leads to renal
      vascular rarefaction, fibrosis and renal failure. Treatment of renovascular
      hypertension remains a challenge, and thus, new therapies are needed. In this
      report, we discuss the beneficial effects of mesenchymal stem cells on the
      reconstruction of the renal parenchyma of the stenotic kidney to improve vascular
      rarefaction and fibrosis. Mesenchymal stem cell therapy prevented the progressive
      increase in systolic arterial pressure, reduced sympathetic hyperactivity,
      improved renal morphology, induced neovascularization and reduced fibrosis in
      stenotic kidneys. Although this therapy may be a promising strategy to treat
      renovascular hypertension and its renal consequences, further studies are
      necessary to improve the efficiency of mesenchymal stem cells.

PMID- 25605445
TI  - Within- and between-city contrasts in nitrogen dioxide and mortality in 10
      Canadian cities; a subset of the Canadian Census Health and Environment Cohort
      (CanCHEC).
AB  - The independent and joint effects of within- and between-city contrasts in air
      pollution on mortality have been investigated rarely. To examine the differential
      effects of between- versus within-city contrasts in pollution exposure, we used
      both ambient measurements and land use regression models to assess associations
      with mortality and exposure to nitrogen dioxide (NO2) among ~735,600 adults in 10
      of the largest Canadian cities. We estimated exposure contrasts partitioned into
      within- and between-city contrasts, and the sum of these as overall exposures,
      for every year from 1984 to 2006. Residential histories allowed us to follow
      subjects annually during the study period. We calculated hazard ratios (HRs)
      adjusted for many personal and contextual variables. In fully-adjusted, random
      effects models, we found positive associations between overall NO2 exposures and
      mortality from non-accidental causes (HR per 5 p.p.b.: 1.05; 95% confidence
      interval (CI): 1.03-1.07), cardiovascular disease (HR per 5 p.p.b.: 1.04; 95% CI:
      1.01-1.06), ischaemic heart disease (HR per 5 p.p.b.: 1.05; 95% CI: 1.02-1.08)
      and respiratory disease (HR per 5 p.p.b.: 1.04; 95% CI: 0.99-1.08), but not from
      cerebrovascular disease (HR per 5 p.p.b.: 1.01; 95% CI: 0.96-1.06). We found that
      most of these associations were determined by within-city contrasts, as opposed
      to by between-city contrasts in NO2. Our results suggest that variation in NO2
      concentrations within a city may represent a more toxic mixture of pollution than
      variation between cities.

PMID- 25605446
TI  - Urinary polycyclic aromatic hydrocarbon metabolites as biomarkers to woodsmoke
      exposure - results from a controlled exposure study.
AB  - Woodsmoke contains harmful components - such as fine particulate matter (PM2.5)
      and polycyclic aromatic hydrocarbons (PAHs) - and impacts more than half of the
      global population. We investigated urinary hydroxylated PAH metabolites (OH-PAHs)
      as woodsmoke exposure biomarkers in nine non-smoking volunteers experimentally
      exposed to a wood fire. Individual urine samples were collected from 24-h before
      to 48-h after the exposure and personal PM2.5 samples were collected during the 2
      h woodsmoke exposure. Concentrations of nine OH-PAHs increased by 1.8-7.2 times
      within 2.3-19.3 h, and returned to baseline approximately 24 h after the
      exposure. 2-Naphthol (2-NAP) had the largest post-exposure increase and exhibited
      a clear excretion pattern in all participants. The level of urinary OH-PAHs,
      except 1-hydroxypyrene (1-PYR), correlated with those of PM2.5, levoglucosan and
      PAHs in personal PM2.5 samples. This finding suggests that several urinary OH
      PAHs, especially 2-NAP, are potential exposure biomarkers to woodsmoke; by
      contrast, 1-PYR may not be a suitable biomarker. Compared with levoglucosan and
      methoxyphenols - two other urinary woodsmoke biomarkers that were measured in the
      same study and reported previously - OH-PAHs might be better biomarkers based on
      sensitivity, robustness and stability, particularly under suboptimal sampling and
      storage conditions, like in epidemiological studies carried out in less developed
      areas. 

PMID- 25605449
TI  - Companion diagnostics at the intersection of personalized medicine and healthcare
      delivery.

PMID- 25605450
TI  - Roadblocks preventing personalized medicine from reaching its potential.

PMID- 25605447
TI  - Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9)
      at different threshold concentrations of tap water arsenic.
AB  - Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease,
      yet the mechanisms involved are not clearly understood. Elevated matrix
      metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as
      well as with exposure to water As. Our objective was to evaluate the effects of
      dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at
      differing levels of tap water As. In a cross-sectional study of 214 adults,
      dietary iAs intake was estimated from 24-h dietary recall interviews using
      published iAs residue data; drinking and cooking water As intake from water
      samples and consumption data. Aggregate iAs intake (food plus water) was
      associated with elevated serum MMP-9 in mixed model regression, with and without
      adjustment for covariates. In models stratified by tap water As, aggregate intake
      was a significant positive predictor of serum MMP-9 in subjects exposed to water
      As<=10 MUg/l. Inorganic As from food alone was associated with serum MMP-9 in
      subjects exposed to tap water As<=3 MUg/l. Exposure to iAs from food and water
      combined, in areas where tap water As concentration is <=10 MUg/l, may contribute
      to As-induced changes in a biomarker associated with toxicity.

PMID- 25605448
TI  - Large-scale in vitro expansion of human regulatory T cells with potent
      xenoantigen-specific suppression.
AB  - Xenotransplantation is a potential solution to the organ donor shortage.
      Immunosuppression is required for successful application of xenotransplantation
      but may lead to infection and cancer. Thus, strategies for immune tolerance
      induction need to be developed. Polyclonal regulatory T cells (Treg) play a
      central role in the induction and maintenance of immune tolerance and have been
      shown to protect against islet xenograft rejection in vivo. However, global
      immune suppression may be mediated by polyclonal Treg immunotherapy and a simple
      method for in vitro expansion of xenoantigen-specific Treg for efficient Treg
      application becomes necessary. Human Treg isolated from peripheral blood
      mononuclear cells (PBMCs) were initially cultured with anti-CD3/CD28 beads,
      rapamycin and IL-2 for 7 days as polyclonal expansion. Expanded Treg were then
      cocultured with irradiated porcine PBMC as xenoantigen stimulation for three
      subsequent cycles with 7 days for each cycle in the presence of IL-2 and anti
      CD3/CD28 beads. Treg phenotype and suppressive capacity were assessed after each
      cycle of xenoantigen stimulation. Treg expanded with one cycle of xenoantigen
      stimulation retained Treg suppressive phenotype but acquired no xenoantigen
      specificity along with poor expansion efficiency, whereas expansion with two
      cycle xenoantigen stimulation resulted in not only more than 800-fold Treg
      expansion but highly suppressive xenoantigen-specific Treg with effector Treg
      phenotype. However further increase of stimulation cycles resulted in reduced
      Treg suppressive potency. This study provides a simple approach to obtain high
      numbers of xenoantigen-specific Treg for immune tolerance induction in
      xenotransplantation. 

PMID- 25605452
TI  - Biomarker use is associated with reduced clinical trial failure risk in
      metastatic melanoma.
AB  - Given the high morbidity and mortality associated with metastatic melanoma,
      considerable attention has been paid to identifying potential therapies. Until
      recently, few therapies have been specifically approved for treating metastatic
      melanoma. In an attempt to increase clinical trial successes, many therapies are
      implementing biomarkers for patient stratification. This strategy narrows down
      the population in an effort to identify appropriate subpopulations that have
      increased efficacy or fewer safety concerns. However, the addition of a biomarker
      constitutes an additional risk to clinical development and may therefore increase
      the overall clinical trial risk. Here, we examine the clinical trial success rate
      for therapies targeting metastatic melanoma. In addition, we identify the impact
      that biomarkers have had on the clinical development of this disease. 

PMID- 25605453
TI  - Complementary versus companion diagnostics: apples and oranges?
AB  - There have been several major problems that have plagued biopharmaceutical
      development since the end of the 1990s, but two in particular have reached the
      point where they are impacting the economic viability of the industry: the lack
      of efficacy of new drugs and increasing competition among therapeutics that
      broadly attack certain common diseases and disease areas. The US FDA has noted
      that the era of one-size-fits-all treatment may well be reaching its end days as
      companies increasingly adopt approaches that involve biomarkers (there are now
      commercial databases that purport to track over 11,000 of them). Pharmacogenomic
      biomarkers in particular are used to create diagnostics that help to
      differentiate or stratify the likely outcomes a patient will experience with a
      drug, which can now be said to be targeted or tailored to patients with
      particular traits (i.e., personalized), leading to an era of so-called precision
      medicine. As more is understood about diseases and the why and how of their
      effects on people through advances in biomarkers and genomics, personalized
      medicine is becoming a natural result of biomedical science and a natural
      trajectory for the innovation-based biopharmaceutical industry. The focus of this
      article is to examine an apparent divergence in that trajectory engendered by a
      growing differentiation in the approaches to personalized medicines in terms of
      their accompanying diagnostics: companion diagnostics are typically linked to a
      specific drug within its approved label, while complementary diagnostics are
      associated more broadly, usually not with a specific drug but with a class of
      drugs, and not confined to specific uses by labeling, with consequent
      ramifications for economic, regulatory and strategic considerations. 

PMID- 25605454
TI  - HER2 testing and its predictive utility in anti-HER2 breast cancer therapy.
AB  - Breast cancer treatment is dependent on accurate pathologic diagnosis. HER2
      testing is now universally recommended as part of evaluation of invasive breast
      cancer. HER2 testing is available via various slide and non-slide based assays,
      and interpretation of results continues to evolve. Herein we review these testing
      modalities and their incorporation into the 2013 ASCO/CAP guidelines. Once
      accurate HER2 status has been established the proper treatment based on recent
      clinical trials can be instituted. 

PMID- 25605455
TI  - Getting the best out of thiopurine therapy: thiopurine S-methyltransferase and
      beyond.
AB  - Thiopurines are the cornerstone of treatment for a wide variety of medical
      disorders, ranging from pediatric leukemia to inflammatory bowel disease. Because
      of their complex metabolism and potential toxicities, the use of biomarkers to
      predict risk and response is paramount. Thiopurine S-methyltransferase and
      thiopurine metabolite levels have emerged as companion diagnostics with crucial
      roles in facilitating safe and effective treatment. This review serves to update
      the reader on how these tools are being developed and implemented in clinical
      practice. A useful paradigm in thiopurine therapeutic strategy is presented,
      along with fresh insights into the mechanisms underlying these approaches. We
      elaborate on potential future developments in the optimization of thiopurine
      therapy. 

PMID- 25605456
TI  - Regulatory considerations for companion diagnostic devices.
AB  - The emergence of companion diagnostic devices has been spurred by drug discovery
      and development efforts towards targeted therapies, particularly in oncology.
      Companion diagnostics and their corresponding therapeutics are often codeveloped,
      or developed in parallel, to ensure the safe and effective use of the products.
      The regulatory framework for companion diagnostics has gradually evolved as a
      result of the essential role of diagnostic tests to identify the intended
      population for a corresponding treatment. Here, we describe the current
      regulatory model for companion diagnostics in the US and outline key strategies
      for a successful codevelopment program from the device perspective. We also
      discuss how technological advances and changes in clinical management may
      challenge the regulatory model in the future. 

PMID- 25605444
TI  - Noninvasive effects measurements for air pollution human studies: methods,
      analysis, and implications.
AB  - Human exposure studies, compared with cell and animal models, are heavily relied
      upon to study the associations between health effects in humans and air pollutant
      inhalation. Human studies vary in exposure methodology, with some work conducted
      in controlled settings, whereas other studies are conducted in ambient
      environments. Human studies can also vary in the health metrics explored, as
      there exists a myriad of health effect end points commonly measured. In this
      review, we compiled mini reviews of the most commonly used noninvasive health
      effect end points that are suitable for panel studies of air pollution, broken
      into cardiovascular end points, respiratory end points, and biomarkers of effect
      from biological specimens. Pertinent information regarding each health end point
      and the suggested methods for mobile collection in the field are assessed. In
      addition, the clinical implications for each health end point are summarized,
      along with the factors identified that can modify each measurement. Finally, the
      important research findings regarding each health end point and air pollutant
      exposures were reviewed. It appeared that most of the adverse health effects end
      points explored were found to positively correlate with pollutant levels,
      although differences in study design, pollutants measured, and study population
      were found to influence the magnitude of these effects. Thus, this review is
      intended to act as a guide for researchers interested in conducting human
      exposure studies of air pollutants while in the field, although there can be a
      wider application for using these end points in many epidemiological study
      designs. 

PMID- 25605459
TI  - Possible atomoxetine-induced vitiligo: a case report.
AB  - Vitiligo is a chronic skin disease characterized by the appearance of white
      depigmented lesion due to a loss of melanocytes. The etiopathogenesis of vitiligo
      is not clear, but according to the neural theory of vitiligo, the direct and
      indirect effects of monoamine neurotransmitters cause melanocyte destruction and
      various studies have supported this theory. Many drugs have been related to the
      development of vitiligo, and the melanocytotoxic effects of the some of these
      drugs are thought to be related due to their effects on the monoaminergic system.
      Furthermore, a recent article reported the development of a localized loss of
      pigmentation after the application of a methylphenidate patch in a patient with
      attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is an inhibitor of
      norepinephrine reuptake sites and is a drug that has been used for the treatment
      of ADHD. Here, we present a school-aged child with ADHD who displayed a vitiligo
      lesion following the initiation of atomoxetine. We further discuss the possible
      impact of the ADHD drugs on the development of vitiligo. 

PMID- 25605458
TI  - Autophagy activation and protection from mitochondrial dysfunction in human
      chondrocytes.
AB  - OBJECTIVE: Autophagy is a key pathway of cellular homeostasis for removing
      damaged macromolecules and organelles, including mitochondria. Recent studies
      indicate that activation of autophagy is defective in aging and osteoarthritis
      (OA), contributing to cell death and tissue damage. In addition, there is
      increasing evidence that mitochondrial dysfunction plays an important role in OA
      pathogenesis. The objective of this study was to determine whether activation of
      autophagy protects against mitochondrial dysfunction in human chondrocytes.
      METHODS: Human chondrocytes were treated with oligomycin, an inhibitor of
      mitochondrial respiratory chain complex V. Autophagy activation was analyzed by
      determination of light chain 3 membrane-bound form II (LC3-II), a marker of
      autophagosome formation. To investigate whether autophagy protects from
      mitochondrial dysfunction, autophagy was induced by rapamycin, the selective
      inhibitor of mammalian target of rapamycin complex 1 (mTORC-1), and by torin 1,
      the inhibitor of mTORC-1 and mTORC-2. Small interfering autophagy-related 5 was
      used to evaluate the role of autophagy in mitochondrial dysfunction. RESULTS:
      Mitochondrial dysfunction was induced by treatment with oligomycin, which
      significantly decreased mitochondrial membrane potential (DeltaPsim). This was
      associated with increased production of reactive oxygen species and cell death.
      Autophagy activation, as reflected by LC3-II, was decreased in a time-dependent
      manner. To evaluate whether autophagy regulates mitochondrial function,
      chondrocytes were pretreated with rapamycin and torin 1 before oligomycin.
      Autophagy activation significantly protected against mitochondrial dysfunction.
      Conversely, genetic inhibition of autophagy induced significant mitochondrial
      function defects. CONCLUSION: Our data highlight the role of autophagy as a
      critical protective mechanism against mitochondrial dysfunction. Pharmacologic
      interventions that enhance autophagy may have chondroprotective activity in
      cartilage degenerative processes such as OA.

PMID- 25605460
TI  - A novel tuberculosis antigen identified from human tuberculosis granulomas.
AB  - Tuberculosis is a global infectious disease caused by Mycobacterium tuberculosis
      (Mtb). Although novel Mtb biomarkers from both the pathogen and host have been
      studied, more breakthroughs are still needed to meet different clinic
      requirements. In an effort to identify Mtb antigens, chaperone-peptide complexes
      were purified from TB infected lungs using free-solution isoelectric focusing
      combined with high resolution LTQ Orbitrap Velos mass spectrometry. Antigen
      specific cellular immune responses in vitro were then examined. Those efforts led
      to the identification of six Mtb peptides only identified in Tuberculosis lung
      samples and that were not found in the control samples. Additionally, antigen
      specific IFN-gamma secretion, T-cell proliferation, cytokine expression, and a
      cytotoxic assay were also evaluated. Among the peptides isolated, we identified a
      34 amino acid peptide named PKAp belonging to a serine/threonine-protein kinase,
      as being able to generate Mtb-specific cellular immune responses as noted by
      elevated antigen-specific cytokine secretion levels, increased CD8(+) T-cell
      proliferation and a strong cytotoxic lymphocyte (CTL) response. Moreover, the
      immune stimulating abilities of PKAp were further validated in vivo, with target
      peptide immunized mice showing an increased cellular IFN-gamma in both the lungs
      and spleen without causing immunopathogenesis. In conclusion, we identified novel
      functional Mtb antigens directly from the granulomatous lesions of Tuberculosis
      patients, inducing not only significant antigen-specific IFN-gamma secretion but
      also a marked cytotoxic lymphocyte functional response. These findings indicated
      that PKAp has potential as a novel antigen biomarker for vaccine development. 

PMID- 25605461
TI  - Systematic characterization and prediction of post-translational modification
      cross-talk.
AB  - Post-translational modification (PTM)(1) plays an important role in regulating
      the functions of proteins. PTMs of multiple residues on one protein may work
      together to determine a functional outcome, which is known as PTM cross-talk.
      Identification of PTM cross-talks is an emerging theme in proteomics and has
      elicited great interest, but their properties remain to be systematically
      characterized. To this end, we collected 193 PTM cross-talk pairs in 77 human
      proteins from the literature and then tested location preference and co-evolution
      at the residue and modification levels. We found that cross-talk events
      preferentially occurred among nearby PTM sites, especially in disordered protein
      regions, and cross-talk pairs tended to co-evolve. Given the properties of PTM
      cross-talk pairs, a naive Bayes classifier integrating different features was
      built to predict cross-talks for pairwise combination of PTM sites. By using a 10
      fold cross-validation, the integrated prediction model showed an area under the
      receiver operating characteristic (ROC) curve of 0.833, superior to using any
      individual feature alone. The prediction performance was also demonstrated to be
      robust to the biases in the collected PTM cross-talk pairs. The integrated
      approach has the potential for large-scale prioritization of PTM cross-talk
      candidates for functional validation and was implemented as a web server
      available at http://bioinfo.bjmu.edu.cn/ptm-x/. 

PMID- 25605462
TI  - Succinylome analysis reveals the involvement of lysine succinylation in
      metabolism in pathogenic Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis,
      remains one of the most prevalent human pathogens and a major cause of mortality
      worldwide. Metabolic network is a central mediator and defining feature of the
      pathogenicity of Mtb. Increasing evidence suggests that lysine succinylation
      dynamically regulates enzymes in carbon metabolism in both bacteria and human
      cells; however, its extent and function in Mtb remain unexplored. Here, we
      performed a global succinylome analysis of the virulent Mtb strain H37Rv by using
      high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated
      peptides from digested cell lysates and subsequent peptide identification. In
      total, 1545 lysine succinylation sites on 626 proteins were identified in this
      pathogen. The identified succinylated proteins are involved in various biological
      processes and a large proportion of the succinylation sites are present on
      proteins in the central metabolism pathway. Site-specific mutations showed that
      succinylation is a negative regulatory modification on the enzymatic activity of
      acetyl-CoA synthetase. Molecular dynamics simulations demonstrated that
      succinylation affects the conformational stability of acetyl-CoA synthetase,
      which is critical for its enzymatic activity. Further functional studies showed
      that CobB, a sirtuin-like deacetylase in Mtb, functions as a desuccinylase of
      acetyl-CoA synthetase in in vitro assays. Together, our findings reveal
      widespread roles for lysine succinylation in regulating metabolism and diverse
      processes in Mtb. Our data provide a rich resource for functional analyses of
      lysine succinylation and facilitate the dissection of metabolic networks in this
      life-threatening pathogen. 

PMID- 25605465
TI  - A facile layer-by-layer approach for high-areal-capacity sulfur cathodes.
AB  - A layer-by-layer cathode is developed for high-areal-capacity Li-S batteries via
      a facile approach. Benefitting from the unique structure and favorable adsorption
      properties of the carbon layers, the fabricated cathodes display high capacity
      with superior rate and cycling performance. An areal capacity of as high as 11.3
      mA h cm(-2) is achieved with a six-sulfur-layer cathode. 

PMID- 25605463
TI  - Safety and anti-ulcerogenic activity of a novel polyphenol-rich extract of clove
      buds (Syzygium aromaticum L).
AB  - Despite the various reports on the pharmacology of Clove bud [Syzygium
      aromaticum]-derived essential oil and its major component eugenol, systematic
      information on the bioactivity of clove polyphenols is very limited. Clove buds
      being one of the richest sources of dietary polyphenols with many traditional
      medicinal uses, the present contribution attempted to derive their standardized
      polyphenol-rich extracts as a water soluble free flowing powder (Clovinol)
      suitable for functional food applications, without the issues of its
      characteristic pungency and aroma. The extract was characterized by electrospray
      ionization-time of flight mass spectrometry (ESI-TOF-MS), and investigated for in
      vivo antioxidant, anti-inflammatory and anti-ulcerogenic activities. Clovinol
      showed significant antioxidant and anti-inflammatory effects as measured by
      cellular antioxidant levels, and the ability to inhibit carrageenan-induced paw
      swelling in mice. Further investigations revealed its significant anti
      ulcerogenic activity (>97% inhibition of ethanol-induced stomach ulcers in Wistar
      rats when orally administered at 100 mg per kg b.w.) and up regulation of in vivo
      antioxidants such as superoxide dismutase (SOD), glutathione (GSH), and catalase
      (CAT). Clovinol also reduced the extent of lipid peroxidation among ulcer induced
      rats, indicating its usefulness in ameliorating oxidative stress and improving
      gastrointestinal health, especially upon chronic alcohol consumption. The extract
      was also shown to be safe and suitable for further investigations and development
      upon acute toxicity studies at 5 g per kg body weight and 28 days of repeated
      dose toxicity studies at 2.5 g per kg b.w. 

PMID- 25605464
TI  - Dyspareunia and childbirth: a prospective cohort study.
AB  - OBJECTIVE: To investigate the relationship between mode of delivery, perineal
      trauma and dyspareunia. DESIGN: Prospective cohort study. SETTING: Six maternity
      hospitals in Melbourne, Australia. SAMPLE: A total of 1507 nulliparous women
      recruited in the first and second trimesters of pregnancy. METHOD: Data from
      baseline and postnatal questionnaires (3, 6, 12 and 18 months) were analysed
      using univariable and multivariable logistic regression. MAIN OUTCOME MEASURE:
      Study-designed self-report measure of dyspareunia at 18 months postpartum.
      RESULTS: In all, 1244/1507 (83%) women completed the baseline and all four
      postpartum questionnaires; 1211/1237 (98%) had resumed vaginal intercourse by 18
      months postpartum, with 289/1211 (24%) women reporting dyspareunia. Compared with
      women who had a spontaneous vaginal delivery with an intact perineum or unsutured
      tear, women who had an emergency caesarean section (adjusted odds ratio [aOR]
      2.41, 95% confidence interval [95% CI] 1.4-4.0; P = 0.001), vacuum extraction
      (aOR 2.28, 95% CI 1.3-4.1; P = 0.005) or elective caesarean section (aOR 1.71,
      95% CI 0.9-3.2; P = 0.087) had increased odds of reporting dyspareunia at 18
      months postpartum, adjusting for maternal age and other potential confounders.
      CONCLUSIONS: Obstetric intervention is associated with persisting dyspareunia.
      Greater recognition and increased understanding of the roles of mode of delivery
      and perineal trauma in contributing to postpartum maternal morbidities, and ways
      to prevent postpartum dyspareunia where possible, are warranted.

PMID- 25605466
TI  - Biofilm and multidrug resistance in uropathogenic Escherichia coli.
AB  - CONTEXT: Escherichia coli is known as causative agent of urinary tract infections
      (UTIs) tends to form microcolonies in mucosa lining of urinary bladder known as
      biofilm. These biofilms make the organism to resist the host immune response,
      more virulent and lead to the evolution of antibacterial drug resistance by
      enclosing them in an extracellular biochemical matrix. AIMS: This study was done
      to know the association of various virulence factors and biofilm production in
      uropathogenic E. coli (UPEC) and antibiotic susceptibility pattern. SETTINGS AND
      DESIGN: This study was conducted in Pt. B.D. Sharma PGIMS, Rohtak, Haryana during
      a period of 1 year from January 2011 to December 2011. METHODS AND MATERIAL:
      Biofilm was detected by microtiter plate (MTP) method, and various virulence
      factors like hemolysin, hemagglutination, gelatinase, siderophore production,
      serum resistance, and hydrophobicity were detected. The antibiotic susceptibility
      testing was done by modified Kirby-Bauer disk diffusion and the disk diffusion
      method was used to confirm the ESBL, AmpC, MBL production by the UPEC statistical
      analysis used: The data were analyzed by using SPSS version 17.0. A two-sided P
      value of less than or equal to 0.05 was considered to be significant. RESULTS:
      Biofilm production was found in 18 (13.5%) isolates, more commonly in females
      (two times). These isolates were found to be resistant to antibiotics common in
      use and were 100% MDR. CONCLUSIONS: Biofilm production makes the organism to be
      more resistant to antibiotics and virulent as compared to non-biofilm producers.

PMID- 25605467
TI  - Brachiocephalic pseudoaneurysm and superior vena cava fistula in an adult with a
      Blalock-Taussig shunt.

PMID- 25605468
TI  - Ten false beliefs about cortisol in critically ill patients.

PMID- 25605470
TI  - Why candidemia occurs early: a comment on "incidence, characteristics and outcome
      of ICU-acquired candidemia in India".

PMID- 25605469
TI  - Effectiveness of treatment based on PiCCO parameters in critically ill patients
      with septic shock and/or acute respiratory distress syndrome: a randomized
      controlled trial.
AB  - PURPOSE: To compare treatment based on either PiCCO-derived physiological values
      or central venous pressure (CVP) monitoring, we performed a prospective
      randomized controlled trial with group sequential analysis. METHODS: Consecutive
      critically ill patients with septic shock and/or ARDS were included. The planned
      total sample size was 715. The primary outcome was 28-day mortality after
      randomization. Participants underwent stratified randomization according to the
      classification of ARDS and/or septic shock. Caregivers were not blinded to the
      intervention, but participants and outcome assessors were blinded to group
      assignment. RESULTS: The study was stopped early because of futility after
      enrollment of 350 patients including 168 in the PiCCO group and 182 in the
      control group. There was no loss to follow-up and data from all enrolled
      participants were analyzed. The result showed that treatment based on PiCCO
      derived physiological values was not able to reduce the 28-day mortality risk
      (odds ratio 1.00, 95 % CI 0.66-1.52; p = 0.993). There was no difference between
      the two groups in secondary outcomes such as 14-day mortality (40.5 vs. 41.2 %; p
      = 0.889), ICU length of stay (median 9 vs. 7.5 days; p = 0.598), days free of
      vasopressors (median 14.5 vs. 19 days; p = 0.676), and days free of mechanical
      ventilation (median 3 vs. 6 days; p = 0.168). No severe adverse event was
      reported in both groups. CONCLUSION: On the basis of our study, PICCO-based fluid
      management does not improve outcome when compared to CVP-based fluid management.

PMID- 25605471
TI  - Critical care infections and antimicrobial resistance are complex multifactorial
      problems.

PMID- 25605473
TI  - Cryoglobulinemia precipitated by targeted temperature management.

PMID- 25605474
TI  - Understanding the differences among inotropes.

PMID- 25605472
TI  - Our paper 20 years later: 1-year survival and 6-month quality of life after
      intensive care.
AB  - INTRODUCTION: In the early 1990s, the in-hospital mortality rate of intensive
      care unit (ICU) patients dropped, and interest in the quality of life (QOL) of
      ICU survivors increased. In 1996, we published a study to investigate 1-year
      survival after hospital discharge and 6-month QOL after intensive care. Now, we
      compare our previous results with those reported in the recent literature to
      appraise any changes, and new knowledge in the area. RESULTS: The 1-year survival
      of ICU patients after hospital discharge is substantial, lower than in the
      general population, and different among subgroups. Some studies showed a
      reduction in QOL at 6 months, as in our study, while others showed an
      improvement. Different results seem to be related mainly to the case mix. Studies
      on different types of patients found long-term cognitive impairment in ICU
      survivors, possibly not disease specific. The proportions of patients with
      neuropsychological morbidities such as posttraumatic stress disorder, anxiety,
      and depression, described after our study, did not show any change over time.
      CONCLUSIONS: Differences between studies on long-term survival and QOL do not
      allow conclusions to be drawn about change over time. No change was found in
      neuropsychological morbidities. However, a lack of change may not be viewed
      negatively, because critically ill patients who survive ICU today may be at
      higher risk for poor long-term outcome than in the past due to the higher
      severity of their illness and the more aggressive treatments received. Future
      studies may provide understanding of the relationships between psychiatric
      symptoms, cognitive impairment, functional disability, and QOL.

PMID- 25605475
TI  - Regional lymph node status after neoadjuvant chemoradiation of rectal cancer
      producing a complete or near complete rectal wall response.
AB  - AIM: Transanal excision of the tumour site after complete response to
      chemoradiotherapy can determine the rectal wall response to treatment. This study
      was designed to assess whether the absence of tumour in the rectal wall
      corresponds to the absence of tumour in the mesorectum (true pathological
      complete response). METHOD: A retrospective review identified patients who
      underwent preoperative chemoradiation therapy for advanced mid and low rectal
      cancer followed by routine pre-planned radical surgery with total mesorectal
      excision. Patients in whom the pathology specimen showed no residual tumour in
      the rectal wall (ypT0) or a ypT1 lesion were assessed for tumour involvement in
      the mesorectum. RESULTS: Seventy-eight patients who underwent pelvic
      chemoradiation followed by radical surgery were reviewed. The rectal wall tumour
      disappeared in eight (ypT0). Of these, residual tumour was found in the
      mesorectum (ypT0N1) in one (12%) patient. Eleven patients were found to have ypT1
      residual tumour. Of these, two (18%) had a final post-surgical staging of ypT1N1.
      CONCLUSION: Complete rectal wall tumour eradication was achieved in 10% of the
      patients, and downstaging to ypT1 was achieved in 14%. In 15% (12% in ypT0 and
      18% in ypT1) of these patients, residual tumour cells were evident in the
      mesorectum. This would probably have rendered these patients with residual
      disease had a nonradical approach of transanal excision of the original tumour
      site been employed. Caution should be taken when considering the avoidance of
      radical surgery.

PMID- 25605476
TI  - Direct oxidative arylation of aryl C - H bonds with aryl boronic acids via pd
      catalysis directed by the N,N-dimethylaminomethyl group.
AB  - Biaryl skeletons were directly constructed via palladium-catalyzed ortho
      arylation of N,N-dimethyl benzylamine with aryl boronic acids with high
      efficiency and high regioselectivity under open-flask conditions. The N,N
      dimethylaminomethyl group was first applied as a directing group in such an
      oxidative coupling. Various substrates proved to be efficient coupling partners,
      furnishing the corresponding ortho-monoarylated or -diarylated arenes in moderate
      to good yields under mild conditions. 

PMID- 25605477
TI  - Perceptions and utilization of the anti-malarials artemether-lumefantrine and
      dihydroartemisinin-piperaquine in young children in the Chikhwawa District of
      Malawi: a mixed methods study.
AB  - BACKGROUND: Adherence to anti-malarial dosing schedules is essential to ensure
      effective treatment. Measuring adherence is challenging due to recall issues and
      the participants' awareness of the desired behaviour influencing their actions or
      responses. This study used qualitative methods, which allow for rapport building,
      to explore issues around anti-malarial utilization in young children, and used
      the results to guide the development of a context specific questionnaire on
      perceptions and adherence to artemether-lumefantrine (AL) and dihydroartemisinin
      piperaquine (DHA-PPQ). METHODS: Qualitative data collection included 12 focus
      group discussions which explored community perceptions of anti-malarials and
      experiences of administering medications to children. Critical incidence
      interviews were conducted with 22 caregivers to explore experiences of
      administering the dispersible or original formulation of AL to young children
      during recent febrile episodes. A structured questionnaire was used to gather
      data on experience of recent treatment and adherence to anti-malarials during
      follow-up visits with 218 caregivers whose child was recently treated with either
      dispersible AL or DHA-PPQ. DISCUSSION/CONCLUSION: Caregivers experience great
      difficulty in administering medication to children. While the sweet taste of
      dispersible AL may have reduced conflict between the child and caregiver, sub
      optimal dosing due to medication loss remained a problem and overall adherence
      was greater among those receiving DHA-PPQ, which requires fewer doses. Some
      caregivers were found to deliberately alter the dosing schedule according to
      whether they perceived the medication to be too weak or strong. They also
      developed theories for poor treatment outcomes, such as attributing this to lack
      of compatibility between the medication and the child. Health education messages
      should be strengthened to ensure a combination of clear pictorial and verbal
      instructions are used during dispensing, and consequences of under and over
      dosing are explained alongside appropriate responses to possible adverse events.
      Further optimizing of anti-malarial adherence among children requires the
      development of anti-malarials with pharmacological properties that allow user
      friendly administration and simplified dosing schedules.

PMID- 25605478
TI  - Beta-cell destruction and preservation in childhood and adult onset type 1
      diabetes.
AB  - Previous studies describing the symptomatic onset of type 1 diabetes (T1D) and
      rate of beta-cell loss (C-peptide) support the notion that childhood onset T1D
      exhibits more severe beta-cell depletion compared to adult onset T1D. To test
      this notion, we performed whole pancreas analyses in two T1D cases, one of
      childhood onset (7-year old, onset at 1.5-year) along with an adult onset case
      (43-year old with onset at 27-year). Both cases were matched for age and gender
      with control subjects. Striking regional differences in beta-cell loss were
      observed in both T1D cases, with severity of loss in the order of tail > body >
      head regions. In contrast, pancreatic alpha- and delta-cell mass was similar in
      controls and T1D patients. In the childhood onset T1D case, no intra-islet beta
      cells were detected while in the adult onset case, beta-cell containing islets
      were found, exclusively in the head region. In the latter case, considerable
      numbers of small cellular clusters negative for three major endocrine hormones
      were observed, in islets with or without beta-cells. Ultrastructural analysis
      suggests these cells correspond to degenerating beta-cells, with empty granular
      membranes and abnormal morphology of nuclei with intranuclear pseudo-inclusions,
      adjacent to healthy alpha- and delta-cells. These results support a hypothesis
      that during T1D development in childhood, beta-cells are more susceptible to
      autoimmune destruction or immune attack is more severe, while beta-cell death in
      the adult onset T1D may be more protracted and incomplete. In addition, T1D may
      be associated with the formation of "empty" beta-cells, an interesting population
      of cells that may represent a key facet to the disorder's pathogenesis.

PMID- 25605479
TI  - Comparing risk behaviours of human papillomavirus-vaccinated and non-vaccinated
      women.
AB  - BACKGROUND: Since September 2008, a national vaccine programme in the UK has
      offered routine human papillomavirus (HPV) vaccination to young women aged 12-13
      years. A catch-up programme also offered HPV vaccination to women born after 1
      September 1990. AIM: To compare indicators of risk and preventive behaviours
      among young women attending genitourinary medicine (GUM) clinics who had, and had
      not, received at least one dose of HPV vaccine. METHODS: Clinical histories and
      HPV vaccination status were obtained from 363 participants eligible for HPV
      vaccination (Cervarix((r))) in the UK vaccination programme (born after 1
      September 1990) attending GUM clinics in the North West of England. Using
      logistic regression, markers of sexual and non-sexual risk behaviours were
      compared between vaccinated and unvaccinated women. RESULTS: At least one dose of
      HPV vaccine had been received by 63.6% (n=231) of participants. Unvaccinated
      women demonstrated higher levels of risky behaviour than those who had undergone
      HPV vaccination. Unvaccinated women were significantly more likely to have had
      three or more partners in the last 6 months, attended the clinic with symptoms,
      not used a condom at first sexual intercourse, had anal intercourse with their
      last sexual contact, to have tested positive for Chlamydia trachomatis diagnosis
      at the clinic visit and to be a current smoker. CONCLUSIONS: In the UK, where
      vaccine coverage is high, failure to initiate HPV vaccination amongst GUM
      attendees is a marker of high-risk behaviours. As a result, HPV vaccination
      status should be ascertained as part of an individual's clinical history by
      sexual health services to ensure advice and counselling is provided to those at
      greatest risk of HPV-associated disease.

PMID- 25605480
TI  - Does research into contraceptive method discontinuation address women's own
      reasons? A critical review.
AB  - OBJECTIVE: To examine the clinical and epidemiological literature addressing
      contraceptive method change or discontinuation and to assess whether the
      documented reasons reflected women's experiences. METHODS: Major databases
      including Medline and PsycINFO were searched using keywords related to
      contraception and discontinuation, adherence and satisfaction, for articles
      published between January 2003 and February 2013. Studies in developed countries
      that focused on women of reproductive age and reasons for method change or
      discontinuation were included. Reasons reported were categorised and examined.
      RESULTS: A total of 123 papers were reviewed in detail. Medical terminology was
      generally used to describe reasons for method discontinuation. The top two
      reported reasons were bleeding and pregnancy, but there was a lack of consensus
      about the categorisation of reasons. Broad categories that were not self
      explanatory were included in more than half of the papers, often without further
      explanation. Only 12 studies expanded on categories containing 'other', 'non
      medical' or 'personal' reasons. Eight papers included categories that attributed
      discontinuation to the participant, such as 'dissatisfied with method'.
      CONCLUSIONS: Studies of reasons for discontinuation of contraceptives do not well
      describe women's specific reasons. Studies rely heavily on medical terms and
      often fail to document women's subjective experiences. Future studies should
      create an opportunity for women to articulate their non-medical reasons in their
      own words, including those related to their sexual lives. Furthermore,
      researchers should distinguish, if possible, between reasons for discontinuation
      of a method and reasons for ceasing participation in a research study.

PMID- 25605481
TI  - Systematic review of surgery and outcomes in patients with primary aldosteronism.
AB  - BACKGROUND: Primary aldosteronism (PA) is the most common cause of secondary
      hypertension. The main aims of this paper were to review outcome after surgical
      versus medical treatment of PA and partial versus total adrenalectomy in patients
      with PA. METHODS: Relevant medical literature from PubMed, the Cochrane Library
      and Embase OvidSP from 1985 to June 2014 was reviewed. RESULTS: Of 2036 records,
      43 articles were included in the final analysis. Twenty-one addressed surgical
      versus medical treatment of PA, four considered partial versus total
      adrenalectomy for unilateral PA, and 18 series reported on surgical outcomes.
      Owing to the heterogeneity of protocols and reported outcomes, only a qualitative
      analysis was performed. In six studies, surgical and medical treatment had
      comparable outcomes concerning blood pressure, whereas six showed better outcome
      after surgery. No differences were seen in cardiovascular complications, but
      surgery was associated with the use of fewer antihypertensive medications after
      surgery, improved quality of life, and (possibly) lower all-cause mortality
      compared with medical treatment. Randomized studies indicate a role for partial
      adrenalectomy in PA, but the high rate of multiple adenomas or adenoma combined
      with hyperplasia in localized disease is disconcerting. Surgery for unilateral
      dominant PA normalized BP in a mean of 42 (range 20-72) per cent and the
      biochemical profile in 96-100 per cent of patients. The mean complication rate in
      1056 patients was 4.7 per cent. CONCLUSION: Recommendations for treatment of PA
      are hampered by the lack of randomized trials, but support surgical resection of
      unilateral disease. Partial adrenalectomy may be an option in selected patients.

PMID- 25605482
TI  - Human leukocyte antigen class I and class II alleles are associated with
      susceptibility and resistance in borderline leprosy patients from Southeast
      Brazil.
AB  - BACKGROUND: Evidence suggests that human leukocyte antigen (HLA) alleles
      influence the host immune response against Mycobacterium leprae. However, the
      association between HLA alleles and borderline (B) leprosy has not been studied.
      The aim of this study was to determine whether HLA class I and II molecules are
      associated with susceptibility or resistance to B leprosy including borderline
      tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL).
      METHODS: DNA was obtained by the salting-out technique from the blood samples of
      202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C*
      loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase
      chain reaction amplification and reverse hybridization with sequence-specific
      oligonucleotide probes and sequence-specific primers. RESULTS: The case
      controlled analysis results showed a significant association between B leprosy
      and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20-0.73, pc =
      0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3
      0.8, pc = 0.039). A protective association was observed between BL leprosy and
      HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15-0.75, pc =
      0.025). In reactional patients, a significant association was observed between
      HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30-5.85, pc =
      0.352) and predisposition to reversal reaction. Haplotype analysis showed that
      A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03
      DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility
      to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01
      haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement
      of these haplotypes in this clinical form of the disease. CONCLUSIONS: The
      results indicate the involvement of HLA class I and class II molecules in B
      leprosy and reversal reactions; it also suggest a role for HLA in polarization of
      the disease in this group of patients.

PMID- 25605483
TI  - Modeling DNA affinity landscape through two-round support vector regression with
      weighted degree kernels.
AB  - BACKGROUND: A quantitative understanding of interactions between transcription
      factors (TFs) and their DNA binding sites is key to the rational design of gene
      regulatory networks. Recent advances in high-throughput technologies have enabled
      high-resolution measurements of protein-DNA binding affinity. Importantly, such
      experiments revealed the complex nature of TF-DNA interactions, whereby the
      effects of nucleotide changes on the binding affinity were observed to be context
      dependent. A systematic method to give high-quality estimates of such complex
      affinity landscapes is, thus, essential to the control of gene expression and the
      advance of synthetic biology. RESULTS: Here, we propose a two-round prediction
      method that is based on support vector regression (SVR) with weighted degree (WD)
      kernels. In the first round, a WD kernel with shifts and mismatches is used with
      SVR to detect the importance of subsequences with different lengths at different
      positions. The subsequences identified as important in the first round are then
      fed into a second WD kernel to fit the experimentally measured affinities. To our
      knowledge, this is the first attempt to increase the accuracy of the affinity
      prediction by applying two rounds of string kernels and by identifying a small
      number of crucial k-mers. The proposed method was tested by predicting the
      binding affinity landscape of Gcn4p in Saccharomyces cerevisiae using datasets
      from HiTS-FLIP. Our method explicitly identified important subsequences and
      showed significant performance improvements when compared with other state-of-the
      art methods. Based on the identified important subsequences, we discovered two
      surprisingly stable 10-mers and one sensitive 10-mer which were not reported
      before. Further test on four other TFs in S. cerevisiae demonstrated the
      generality of our method. CONCLUSION: We proposed in this paper a two-round
      method to quantitatively model the DNA binding affinity landscape. Since the
      ability to modify genetic parts to fine-tune gene expression rates is crucial to
      the design of biological systems, such a tool may play an important role in the
      success of synthetic biology going forward.

PMID- 25605484
TI  - Downregulation of Kinesin spindle protein inhibits proliferation, induces
      apoptosis and increases chemosensitivity in hepatocellular carcinoma cells.
AB  - BACKGROUND: Kinesin spindle protein (KSP) plays a critical role in mitosis.
      Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately
      to cell death. The aim of this study was to suppress KSP expression by specific
      small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor
      activity. METHODS: Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched
      siRNA (Cont-siRNA) were transfected into cells. Subsequently, KSP mRNA and
      protein levels, cell proliferation, and apoptosis were examined in both Hep3B
      cells and THLE-3 cells. In addition, the chemosensitivity of KSP-siRNA-treated
      Hep3B cells with doxorubicin was also investigated using cell proliferation and
      clonogenic survival assays. RESULTS: The expression of endogenous KSP at both
      mRNA and protein levels in Hep3B cells was higher than in THLE-3 cells. In Hep3B
      cells, KSP-siRNA #2 showed a further downregulation of KSP as compared to KSP
      siRNA #1 or KSP-siRNA #3. It also exhibited greater suppression of cell
      proliferation and induction of apoptosis than KSP-siRNA #1 or KSP-siRNA #3; this
      could be explained by the significant downregulation of cyclin D1, Bcl-2, and
      survivin. In contrast, KSP-siRNAs had no or lower effects on KSP expression, cell
      proliferation and apoptosis in THLE-3 cells. We also noticed that KSP-siRNA
      transfection could increase chemosensitivity to doxorubicin in Hep3B cells, even
      at low doses compared to control. CONCLUSION: Reducing the expression level of
      KSP, combined with drug treatment, yields promising results for eradicating
      hepatocellular carcinoma (HCC) cells in vitro. This study opens a new direction
      for liver cancer treatment.

PMID- 25605485
TI  - Expression of two basic mRNA biomarkers in peripheral blood of patients with non
      small cell lung cancer detected by real-time rt-PCR, individually and
      simultaneously.
AB  - INTRODUCTION: Although extensive research has been conducted on lung cancer
      markers, a singular clinically applicable marker has not been found yet. The
      objective of this study was to evaluate the sensitivity and the specificity of
      carcinoembryonic antigen (CEA) mRNA and lung-specific X protein (LUNX) mRNA
      biomarkers in peripheral blood to detect lung cancer individually and
      simultaneously. METHODS: Thirty patients affected by lung cancer and 30 healthy
      individuals were studied in this research. Three vials of cDNA were made from
      each sample after taking peripheral blood samples and extracting total RNA. Each
      sample was examined by the real-time RT-PCR technique. The result from each vial
      was then compared with the sensitivity of overall marker. RESULTS: The CEA mRNA
      was positive in 24 out of 30 lung cancer patients. Hence, its sensitivity was
      determined at 80%, differing significantly from that observed in healthy
      individuals, where 11 positive cases were seen. The overall sensitivity of this
      marker was significantly associated with positivity in vials 2 and 3 but not in
      vial 1. The LUNX mRNA was positive in 21 out of 30 patients, indicating 70%
      sensitivity. This finding significantly differed from that in healthy
      individuals. The overall sensitivity of this marker was significantly associated
      with positivity in vials 1 and 3, but not in vial 2. In 93.3% of the patients, at
      least one positive marker was observed. CONCLUSION: The mentioned mRNA could be
      suggested as sensitive and specific markers in peripheral blood for primary
      diagnosis of lung cancer.

PMID- 25605486
TI  - Comparison of mitochondrial-related transcriptional levels of TFAM, NRF1 and MT
      CO1 genes in single human oocytes at various stages of the oocyte maturation.
AB  - BACKGROUND: The aim of the current study was to assess the mRNA levels of two
      mitochondria-related genes, including nuclear-encoded NRF1 (nuclear respiratory
      factor 1), mitochondrial transcription factor A (TFAM), and mitochondrial-encoded
      cytochrome c oxidase subunit 1 (MT-CO1) genes in various stages of the human
      oocyte maturation. METHODS: Oocytes were obtained from nine infertile women with
      male factor undergoing in vitro fertilization (IVF)/intra-cytoplasmic sperm
      injection protocol. Mitochondrial-related mRNA levels were performed by single
      cell TaqMan real-time PCR. RESULTS: the expression level of the target genes was
      low at the germinal vesicle stage (P>0.05). Although the mRNA level of NRF1gene
      remained stable in metaphase I, the mRNA level of TFAM and MT-CO1 increased
      significantly (P<0.05).In metaphase II, the expression level of all genes
      increased compared to metaphase I (P<0.05). CONCLUSION: The overexpression levels
      of NRF1, TFAM, and MT-CO1 genes are related to the oocyte maturation. Therefore,
      the current study could be used clinically to improve the success rate of IVF.

PMID- 25605487
TI  - Neuronal cell reconstruction with umbilical cord blood cells in the brain hypoxia
      ischemia.
AB  - BACKGROUND: Brain hypoxia-ischemia is a human neonatal injury that is considered
      a candidate for stem cell therapy. METHODS: The possible therapeutic potential of
      human umbilical cord blood (HUCB) stem cells was evaluated in 14-day-old rats
      subjected to the right common carotid occlusion, a model of neonatal brain
      hypoxia-ischemia. Seven days after hypoxia-ischemia, rats received either saline
      solution or 4 * 105 HUCB cells i.v. Rats in control group did not receive any
      injection. After two weeks, rats were assessed using two motor tests.
      Subsequently, rats were scarified for histological and immunohistochemical
      analyses. RESULTS: Our immunohistochemical findings demonstrated selective
      migration of the injected HUCB cells to the ischemic area as well as reduction in
      infarct volume. Seven days after surgery, we found significant recovery in the
      behavioral performance in the test group (12.7 +/- 0.3) compared to the sham
      group (10.0 +/-0.05), a trend which continued to day 14 (15.3 +/- 0.3 vs. 11.9 +/
      0.5, P<0.05). Postural and motor asymmetries at days 7 and 14 in the test group
      showed a significant decrease in the percentage of right turns in comparison to
      the sham group (75% and 59% vs. 97% and 96%, P<0.05). CONCLUSION: The results
      show the potential of HUCB stem cells in reduction of neurologic deficits
      associated with neonatal hypoxia-ischemia.

PMID- 25605488
TI  - Comparative analysis of CD4+ and CD8+ T cells in tumor tissues, lymph nodes and
      the peripheral blood from patients with breast cancer.
AB  - BACKGROUND: CD4+ and CD8+ T cells are the main types of lymphocytes in cell
      mediated immunity and play a central role in the induction of efficient immune
      responses against tumors. The frequencies of T cell subtypes in the peripheral
      blood and tumor tissues, and draining lymph nodes (dLN) can be considered as
      useful markers for evaluation of the immune system in cancers. METHODS: In this
      study, the frequencies of CD4+ and CD8+ T cells in blood, tumor tissues, and dLN
      samples of breast cancer patients were compared with each other and with similar
      tissues from normal individuals. Immunophenotyping was carried out by flow
      cytometry and the expression levels of CXCL10, granzyme B, and mammaglobin were
      evaluated by real-time PCR. RESULTS: In the peripheral blood, there were no
      differences in the T cell subsets between the patients and the normal
      individuals. The frequency of CD8+ T cells was significantly higher in tumor
      tissue than normal breast tissues while granzyme B expression was similar. Based
      on mammaglobin expression levels, dLN have been classified into micro- and macro
      metastatic dLN. We found significantly lower frequency of CD4+ in macro
      metastatic dLN than micro-metastatic dLN. CD8+ frequency was similar in both dLN;
      however, granzyme B expression was higher in micro-metastatic ones. There was not
      any significant difference in CXCL10 expression between the two types of dLN.
      CONCLUSION: Based on our results, although the tumor does not affect the systemic
      immunity, tumoral cells affect the local immune system in the tumoral tissues and
      the metastatic dLN.

PMID- 25605489
TI  - Anticonvulsant effect of Cicer arietinum seed in animal models of epilepsy:
      introduction of an active molecule with novel chemical structure.
AB  - BACKGROUND: Cicer arietinum (Chickpea) is one of the most important harvests in
      the world with high nutritional value. Lack of essential oils in the seeds of
      Chickpea is an advantage in search for drug-like molecules with less toxicity. We
      evaluated anticonvulsant effect of C. arietinum in common animal models of
      epilepsy. METHODS: Dichloromethane extract was obtained from C. arietinum seeds
      by percolation. Acute toxicity of the extract was assessed in mice. Protective
      effect of the extract was examined against tonic seizures induced by maximal
      electroshock (MES; 50 mA, 50 Hz, 1 s) in mice, clonic seizures induced by
      pentylenetetrazole (PTZ; 60 mg/kg, i.p.) in mice, and electrical kindling model
      of complex partial seizures in rats. The extract was fractionated by n-hexane to
      f1 and f2 fractions. The extract and fractions underwent phytochemical analysis
      by thin layer chromatography. The active anticonvulsant fraction, f1, was
      subjected to matrix assisted laser desorption/ionization (MALDI) mass analysis.
      RESULTS: The crude extract had neither toxicity up to 7 g/kg nor protective
      activity in MES and kindling models. However, it significantly inhibited clonic
      seizures induced by PTZ. f1 fraction mimicked protective effect of the extract.
      Phytochemical screening revealed the presence of considerable amount of alkaloids
      in the extract and fractions. Moreover, a novel structural class was detected in
      f1 fraction. CONCLUSION: Finding an anticonvulsant molecule pertaining to a new
      structural class in the seeds of C. arietinum promises an effective and
      inexpensive source of antiepileptic medication. Further studies are needed to
      identify its mechanism of action and more clues into its structure-activity
      relationship.

PMID- 25605490
TI  - Association between p53 codon 72 (Arg72Pro) polymorphism and primary open-angle
      glaucoma in Iranian patients.
AB  - BACKGROUND: Glaucomatous neuropathy is a type of cell death due to apoptosis. The
      p53 gene is one of the regulatory genes of apoptosis. Recently, the association
      between the p53 gene encoding for proline at codon 72 and primary open-angle
      glaucoma (POAG) has been studied in some ethnic groups. This study is the first
      association analysis of POAG and p53 codon 72 polymorphism in Iranian patients.
      METHODS: A cohort of 65 unrelated patients with POAG (age range from 12-62 years,
      mean +/- SD of 40.16 +/- 17.51 years) and 65 unrelated control subjects (without
      glaucoma, age range of 14-63 years, mean +/- SD of 35.64 +/- 13.61 years) were
      selected. In Iranian POAG patients and normal healthy controls, the p53 codon 72
      polymorphism in exon 4 was amplified using polymerase chain reaction. The
      amplified DNA fragments were digested with the BstUI restriction enzyme, and the
      digestion patterns were used to identify the alleles for the polymorphic site.
      RESULTS: Comparisons revealed significant differences in allele and genotype
      frequencies of Pro72Arg between POAG patients and control group. A higher risk of
      POAG was associated with allele Pro (OR = 2.1, 95% CI = 1.2-3.4) and genotype
      Pro/Pro (OR = 3.9, 95% CI = 0.13-12.7). CONCLUSION: The p53 Pro72 allele was more
      frequent in Iranian POAG patients than in the control group (P<0.05). The present
      findings show that the individuals with the Pro/Pro genotype may be more likely
      to develop POAG. However, additional studies are necessary to confirm this
      association.

PMID- 25605493
TI  - Who are we? A qualitative evaluation of trainees' perspectives on professional
      identity in oral and maxillofacial surgery.
AB  - INTRODUCTION: Professional identity is becoming increasingly important in medical
      education in terms of developing appropriately trained and safely practising
      doctors. Oral and maxillofacial surgery (OMFS) is a unique surgical speciality
      that requires dual qualification in medicine and dentistry. Its junior trainees
      move between the various roles of student, doctor and dentist, and at certain
      times these roles may overlap. This heterogeneous early training may raise
      significant barriers for them in terms of understanding their professional
      identity and developing their own sustainable sense of belonging. This study
      looks to understand current trainees' perceptions of the professional identity of
      an oral and maxillofacial surgeon. METHOD: A qualitative research methodology
      based on a grounded theory approach was used in this study. Data were collected
      using in-depth, semi-structured interviews with OMFS specialist trainees.
      Subsequent theories were constructed after thematic analysis. RESULTS: A model of
      the professional identity of an oral and maxillofacial surgeon is proposed.
      DISCUSSION: This study represents the first attempt to understand professional
      identity in OMFS trainees. It will provide insight into what trainees understand
      by the term in this speciality, as well as outlining what trainees feel are
      important elements to develop a sense of belonging within the speciality.

PMID- 25605492
TI  - Glycoconjugates distribution during developing mouse spinal cord motor
      organizers.
AB  - BACKGROUND: The aim of this research was to study the distribution and changes of
      glycoconjugates particularly their terminal sugars by using lectin histochemistry
      during mouse spinal cord development. METHODS: Formalin-fixed sections of mouse
      embryo (10-16 fetal days) were processed for lectin histochemical method. In this
      study, two groups of horseradish peroxidase-labeled specific lectins were used: N
      acetylgalactosamine, including Dolichos biflorus, Wisteria floribunda agglutinin
      (WFA), Vicia villosa, Glycine max as well as focuse-binding lectins, including
      tetragonolobus, Ulex europaeus, and Orange peel fungus (OFA). All sections were
      counterstained with alcian blue (pH 2.5). RESULTS: Our results showed that only
      WFA and OFA reacted strongly with the floor plate cells from early to late
      embryonic period of developing spinal cord. The strongest reactions were related
      to the 14, 15, and 16 days of tissue sections incubated with OFA and WFA lectins.
      CONCLUSION: The present study demonstrated that cellular and molecular
      differentiation of the spinal cord organizers is a wholly regulated process, and
      alpha-L-fucose, alpha-D-GalNAc, and alpha/beta-D-GalNAc terminal sugars play a
      significant role during the prenatal spinal cord development.

PMID- 25605491
TI  - Simultaneous analysis of multidrug resistance 1(MDR1) C3435T, G2677T/A, and
      C1236T genotypes in Hamadan City population, West of Iran.
AB  - BACKGROUND: One of the limitations in the treatment of common diseases such as
      cancer chemotherapy is development of multidrug resistance (MDR). Polymorphisms
      could alter the expression level of MDR1 gene, which plays an important role in
      MDR. In this research, the frequency of C3435T, C1236T, and G2677T/A
      polymorphisms of MDR1 gene was investigated in a large group of population from
      Hamadan city to provide a sample data resource. METHODS: Peripheral blood (2 ml)
      was taken, and DNA extraction was carried out. Multiplexed mutagenically
      separated PCR, which was followed by polyacrylamide gel electrophoresis and
      silver staining, was applied to detect the mentioned polymorphisms in 935
      individuals. Sequencing performed for confirmation of gel electrophoresis
      resulted in 10 random cases. In total, alleles and genotypes of 933 persons (776
      women and 157 men) were determined. RESULTS: The most frequent alleles of the
      polymorphisms were: 3435T, C1236, and G2677. The most frequent genotypes were:
      3435C/T, 1236C/T, and 2677G/A, and their concurrent presence was also found as
      the most frequent simultaneous genotypes. There was not any meaningful difference
      among the prevalence of these genotypes in groups of men and women. CONCLUSION:
      Our results were close to those of other studies performed in Iran and compared
      to the other ethnic groups, which showed more similarity to Asian peoples than
      Europeans. As an aspect of personalized medicine, it could be used by
      chemotherapists to improve the routine methods of cancer treatment.

PMID- 25605494
TI  - Peer-teaching: an important skill for all medical students and doctors?

PMID- 25605495
TI  - Somatosensory stimulation and assisted reproduction.

PMID- 25605496
TI  - Review of Italian primary care paediatricians identifies 38 commonly prescribed
      drugs for children [letter].

PMID- 25605497
TI  - The psychological process of reintegration following a nine month/260 day solo
      sailboat circumnavigation of the globe.
AB  - The focus of this case report is on the psychological reintegration process
      following the achievement of a highly challenging long-duration and solitary
      endeavor. The participant was a 29 year old male who successfully circumnavigated
      the globe during a 260 day solo sailing expedition. We assessed the psychological
      aftermath in terms of stability and change in personality characteristics and
      personal beliefs prior to, and at 180 and 360 days after the completion of the
      journey. Overall, the personality configuration reflected adaptive personality
      functioning. A belief in an internal locus of control was consistent throughout,
      as were perceptions of personal growth as a result of the circumnavigation
      experience. NEO PI-R Neuroticism, Extraversion, Openness, and Triarchic
      Psychopathy Measure (Tri-PM) Boldness scores remained stable. Positive
      personality change was reflected by an elevation in Conscientiousness; negative
      change by a decline in Agreeableness and an increase in Tri-PM Disinhibition.
      While overall the participant exhibited positive change as a result of his
      journey, there were also some negative aspects of the reintegration phase in
      regard to interactions with other persons. This latter change may be related to
      the effects of isolation from usual social contacts over an extended period.

PMID- 25605498
TI  - Brain-computer interface control along instructed paths.
AB  - OBJECTIVE: Brain-computer interfaces (BCIs) are being developed to assist
      paralyzed people and amputees by translating neural activity into movements of a
      computer cursor or prosthetic limb. Here we introduce a novel BCI task paradigm,
      intended to help accelerate improvements to BCI systems. Through this task, we
      can push the performance limits of BCI systems, we can quantify more accurately
      how well a BCI system captures the user's intent, and we can increase the
      richness of the BCI movement repertoire. APPROACH: We have implemented an
      instructed path task, wherein the user must drive a cursor along a visible path.
      The instructed path task provides a versatile framework to increase the
      difficulty of the task and thereby push the limits of performance. Relative to
      traditional point-to-point tasks, the instructed path task allows more thorough
      analysis of decoding performance and greater richness of movement kinematics.
      MAIN RESULTS: We demonstrate that monkeys are able to perform the instructed path
      task in a closed-loop BCI setting. We further investigate how the performance
      under BCI control compares to native arm control, whether users can decrease
      their movement variability in the face of a more demanding task, and how the
      kinematic richness is enhanced in this task. SIGNIFICANCE: The use of the
      instructed path task has the potential to accelerate the development of BCI
      systems and their clinical translation.

PMID- 25605499
TI  - Modification of perpendicular magnetic anisotropy and domain wall velocity in
      Pt/Co/Pt by voltage-induced strain.
AB  - The perpendicular magnetic anisotropy K(eff), magnetization reversal, and field
      driven domain wall velocity in the creep regime are modified in Pt/Co(0.85-1.0
      nm)/Pt thin films by strain applied via piezoelectric transducers. K(eff),
      measured by the extraordinary Hall effect, is reduced by 10 kJ/m(3) by tensile
      strain out-of-plane epsilon(z) = 9 * 10(-4), independently of the film thickness,
      indicating a dominant volume contribution to the magnetostriction. The same
      strain reduces the coercive field by 2-4 Oe, and increases the domain wall
      velocity measured by wide-field Kerr microscopy by 30-100%, with larger changes
      observed for thicker Co layers. We consider how strain-induced changes in the
      perpendicular magnetic anisotropy can modify the coercive field and domain wall
      velocity.

PMID- 25605502
TI  - Glyconanomaterials. Preface.

PMID- 25605500
TI  - Ischaemia-induced autophagy leads to degradation of gap junction protein
      connexin43 in cardiomyocytes.
AB  - GJIC (gap junction intercellular communication) between cardiomyocytes is
      essential for synchronous heart contraction and relies on Cx (connexin)
      containing channels. Increased breakdown of Cx43 has been often associated with
      various cardiac diseases. However, the mechanisms whereby Cx43 is degraded in
      ischaemic heart remain unknown. The results obtained in the present study, using
      both HL-1 cells and organotypic heart cultures, show that simulated ischaemia
      induces degradation of Cx43 that can be prevented by chemical or genetic
      inhibitors of autophagy. Additionally, ischaemia-induced degradation of Cx43
      results in GJIC impairment in HL-1 cells, which can be restored by autophagy
      inhibition. In cardiomyocytes, ubiquitin signals Cx43 for autophagic degradation,
      through the recruitment of the ubiquitin-binding proteins Eps15 (epidermal growth
      factor receptor substrate 15) and p62, that assist in Cx43 internalization and
      targeting to autophagic vesicles, via LC3 (light chain 3). Moreover, we establish
      that degradation of Cx43 in ischaemia or I/R (ischaemia/reperfusion) relies upon
      different molecular players. Indeed, degradation of Cx43 during early periods of
      ischaemia depends on AMPK (AMP-activated protein kinase), whereas in late periods
      of ischaemia and I/R Beclin 1 is required. In the Langendorff-perfused heart,
      Cx43 is dephosphorylated in ischaemia and degraded during I/R, where Cx43
      degradation correlates with autophagy activation. In summary, the results of the
      present study provide new evidence regarding the molecular mechanisms whereby
      Cx43 is degraded in ischaemia, which may contribute to the development of new
      strategies that aim to preserve GJIC and cardiac function in ischaemic heart. 

PMID- 25605501
TI  - Computed tomographic findings in 57 cats with primary pulmonary neoplasia.
AB  - Primary pulmonary neoplasia is relatively uncommon in cats and generally has a
      poor prognosis. In this multicenter, retrospective study of 57 cats with
      pulmonary neoplasia, the most frequent presenting signs were anorexia/inappetence
      (39%) and cough (37%). The pulmonary tumors were considered to be incidental
      findings in 9% cats. In computed tomographic (CT) images, primary pulmonary
      tumors appeared as a pulmonary mass in 55 (96%) cats and as a disseminated
      pulmonary lesion without a defined mass in two (4%) cats. Most pulmonary tumors
      were in the caudal lobes, with 28 (49%) in the right caudal lobe and 17 (30%) in
      the left caudal lobe. CT features associated with pulmonary tumors included mass
      in contact with visceral pleura (96%), irregular margins (83%), well-defined
      borders (79%), bronchial compression (74%), gas-containing cavities (63%), foci
      of mineral attenuation (56%), and bronchial invasion (19%). The mean (range)
      maximal dimension of the pulmonary masses was 3.5 cm (1.1-11.5 cm). Additional
      foci of pulmonary disease compatible with metastasis were observed in 53% cats.
      Pleural fluid was evident in 30% cats and pulmonary thrombosis in 12% cats. The
      histologic diagnoses were 47 (82%) adenocarcinomas, six (11%) tumors of bronchial
      origin, three (5%) adenosquamous cell carcinomas, and one (2%) squamous cell
      carcinoma. In this series, adenocarcinoma was the predominant tumor type, but
      shared many features with less common tumor types. No associations were
      identified between tumor type and CT features. Prevalence of suspected
      intrapulmonary metastasis was higher than in previous radiographic studies of
      cats with lung tumors. 

PMID- 25605503
TI  - Fluoride-promoted esterification with imidazolide-activated compounds: a modular
      and sustainable approach to dendrimers.
AB  - Based on the growing demand for facile and sustainable synthetic methods to
      structurally perfect polymers, we herein describe a significant improvement of
      esterification reactions capitalizing on 1,1'-carbonyldiimidazole (CDI). Cesium
      fluoride was shown to be an essential catalyst for these reactions to reach
      completion. This approach was successfully applied to the synthesis of
      structurally flawless and highly functional polyester dendrimers employing
      traditional and accelerated growth strategies. A sixth generation bis-MPA
      dendrimer with a molecular weight of 22.080 Da and 192 peripheral hydroxy groups
      was isolated in less than one day of total reaction time. Large quantities of
      dendrimers were obtained in high yields (>90%) using simple purification steps
      under sustainable conditions. The fluoride-promoted esterification (FPE) via
      imidazolide-activated compounds is wide in scope and constitutes a potentially
      new approach toward functional polymers and other materials.

PMID- 25605504
TI  - Multistage principal component analysis based method for abdominal ECG
      decomposition.
AB  - Reflection of fetal heart electrical activity is present in registered abdominal
      ECG signals. However this signal component has noticeably less energy than
      concurrent signals, especially maternal ECG. Therefore traditionally recommended
      independent component analysis, fails to separate these two ECG signals.
      Multistage principal component analysis (PCA) is proposed for step-by-step
      extraction of abdominal ECG signal components. Truncated representation and
      subsequent subtraction of cardio cycles of maternal ECG are the first steps. The
      energy of fetal ECG component then becomes comparable or even exceeds energy of
      other components in the remaining signal. Second stage PCA concentrates energy of
      the sought signal in one principal component assuring its maximal amplitude
      regardless to the orientation of the fetus in multilead recordings. Third stage
      PCA is performed on signal excerpts representing detected fetal heart beats in
      aim to perform their truncated representation reconstructing their shape for
      further analysis. The algorithm was tested with PhysioNet Challenge 2013 signals
      and signals recorded in the Department of Obstetrics and Gynecology, Lithuanian
      University of Health Sciences. Results of our method in PhysioNet Challenge 2013
      on open data set were: average score: 341.503 bpm(2) and 32.81 ms. 

PMID- 25605505
TI  - WJU special edition: Surgical and medical management of stones.

PMID- 25605507
TI  - An efficient Volumetric Arc Therapy treatment planning approach for hippocampal
      avoidance whole-brain radiation therapy (HA-WBRT).
AB  - An efficient and simple class solution is proposed for hippocampal-avoidance
      whole-brain radiation therapy (HA-WBRT) planning using the Volumetric Arc Therapy
      (VMAT) delivery technique following the NRG Oncology protocol NRG-CC001 treatment
      planning guidelines. The whole-brain planning target volume (PTV) was subdivided
      into subplanning volumes that lie in plane and out of plane with the hippocampal
      avoidance volume. To further improve VMAT treatment plans, a partial-field dual
      arc technique was developed. Both the arcs were allowed to overlap on the in
      plane subtarget volume, and in addition, one arc covered the superior out-of
      plane sub-PTV, while the other covered the inferior out-of-plane subtarget
      volume. For all plans (n = 20), the NRG-CC001 protocol dose-volume criteria were
      met. Mean values of volumes for the hippocampus and the hippocampal-avoidance
      volume were 4.1 cm(3) +/- 1.0 cm(3) and 28.52 cm(3) +/- 3.22 cm(3), respectively.
      For the PTV, the average values of D(2%) and D(98%) were 36.1 Gy +/- 0.8 Gy and
      26.2 Gy +/- 0.6 Gy, respectively. The hippocampus D(100%) mean value was 8.5 Gy
      +/- 0.2 Gy and the maximum dose was 15.7 Gy +/- 0.3 Gy. The corresponding plan
      quality indices were 0.30 +/- 0.01 (homogeneity index), 0.94 +/- 0.01 (target
      conformality), and 0.75 +/- 0.02 (confirmation number). The median total monitor
      unit (MU) per fraction was 806 MU (interquartile range [IQR]: 792 to 818 MU) and
      the average beam total delivery time was 121.2 seconds (IQR: 120.6 to 121.35
      seconds). All plans passed the gamma evaluation using the 5-mm, 4% criteria, with
      gamma > 1 of not more than 9.1% data points for all fields. An efficient and
      simple planning class solution for HA-WBRT using VMAT has been developed that
      allows all protocol constraints of NRG-CC001 to be met.

PMID- 25605506
TI  - Treatment preferences in stage IA and IB testicular seminoma: multicenter study
      of Anatolian Society of Medical Oncology.
AB  - BACKGROUND: Approximately 75 % of patients with testicular seminoma present with
      stage I disease, and the probability of long-term survival approaches 100 %.
      However, the standard adjuvant treatment for stage I seminoma patients remains
      controversial, and there is no uniform consensus in the literature. The present
      study was performed to evaluate treatment preference and outcomes for men with
      stage I testicular seminoma. MATERIALS AND METHODS: From 1997 to 2013, 282
      patients with histologically confirmed stage IA and IB testicular seminoma who
      underwent orchiectomy were included. The outcomes of three management options and
      survivals were retrospectively analyzed. The prognostic significance of risk
      factors for relapse on survival was evaluated by univariate and multivariate
      analysis; in addition, the factors predicting relapse were also evaluated by
      logistic regression analysis. RESULTS: Of the 282 patients with stage I seminoma,
      130 (46.1) received adjuvant radiotherapy (RT), 80 (28.4 %) were treated with
      adjuvant carboplatin, while the remaining 72 patients (25.5 %) underwent
      surveillance. At the time of analysis, the median follow-up period of 38.5
      months; relapses were observed in 16 patients (22.3 %) on surveillance, in one
      patient (1.2 %) treated with adjuvant carboplatin and in ten patients (%7.7) who
      received adjuvant RT. The 5-year disease-free survival (DFS) rate for patients
      who underwent surveillance was worse than those of patients treated with adjuvant
      carboplatin and RT (64.2 vs. 97.7 vs. 91.9 %, respectively; p < 0.001). However,
      the 5-year overall survival (OS) rate for patients on surveillance was similar
      compared with the adjuvant treatment groups (100 vs. 92.3 vs. 97.4 %,
      respectively; p = 0.44). Univariate analysis showed that only the treatment
      approach (surveillance vs. adjuvant carboplatin vs. adjuvant RT) for DFS (p <
      0.001), invasion of the rete testis (p = 0.041) and the presence of relapse (p <
      0.001) for OS were important prognostic indicators. Multivariate analysis
      indicated that the treatment strategy for DFS (p < 0.001, HR 0.34) was an
      independent prognostic factor. Furthermore, a logistic regression analysis showed
      that adjuvant treatment was found to be an independent factor for predicting
      relapse (p = 0.004, odds ratio: 0.39). CONCLUSIONS: Our results indicate that
      adjuvant treatment with carboplatin or RT is associated with improved DFS
      compared with surveillance for men with stage I testicular seminoma after
      orchiectomy. Moreover, the treatment strategy is an important prognostic
      indicator for DFS and a predictive factor for relapse. Although adjuvant
      treatment, especially carboplatin, seems to be a suitable treatment for patients
      with risk factors for relapse, surveillance is still feasible and the preferred
      management option after radical orchiectomy in men with stage I seminoma. More
      reliable predictive factors are needed to make treatment decisions.

PMID- 25605508
TI  - [Evaluation of satisfaction after hysteroscopic tubal ligation. About a study
      from the CHU of Besancon].
AB  - OBJECTIVE: The Essure((r)) system is a hysteroscopic sterilization method. The
      purpose of our study was to retrospectively evaluate the sterilization procedure
      with Essure((r)) devices without anesthesia. PATIENTS AND METHODS: The
      descriptive study included all tubal sterilizations with Essure((r)) devices
      performed without anesthesia, with MEOPA, from January 1st, 2013 till February
      28th, 2014 in the CHU of Besancon. The evaluation of the global satisfaction of
      the patients was collected by telephone survey. RESULTS: A hundred and forty
      three patients benefited from Essure((r)) without anesthesia during the period of
      study in the CHU of Besancon and among them, 120 patients answered the telephone
      survey questionnaire. The average age was of 41.3 years. As regards the
      satisfaction and the tolerance, 89.2% of the patients declared to be globally
      satisfied by this procedure and 95.8% would recommend it to a friend. Indeed,
      66.6% of the patients declared to have felt no pain or moderate pain.
      Furthermore, the MEOPA was well tolerated at 79.9% of the patients. As regards
      the procedure of Essure((r)) inserts without anesthesia the rate of failure was
      9.2% and at 3 months the radiological control was satisfactory in 94.5% of the
      patients. DISCUSSION AND CONCLUSION: The tubaire sterilization by implants
      Essure((r)) is a fast and effective procedure. Our study shows, that at present,
      this technique can be realized without anesthesia, during a dedicated
      consultation, with an important rate of global satisfaction of the patients. It
      thus allows to decrease the number of hospitalization in ambulatory surgery and
      to decrease the cost of this intervention.

PMID- 25605509
TI  - Management of Stage I Endometrial Cancer in France: A Survey on Current Practice.
AB  - PURPOSE: We conducted a survey to assess the performance of preoperative staging
      and the application of French surgical guidelines in women with presumed stage I
      endometrial cancer (EC). METHODS: The survey included 26 questions about the
      number of patients in low-, intermediate-, and high-risk groups operated on in
      2012, the proportion of patients upstaged or downstaged by the examination of the
      uterus, and the proportion of subsequent surgery for lymph node dissection.
      RESULTS: Thirty-two (70 %) of the 46 French university hospitals responded to the
      questionnaire. Among 886 patients with EC treated, 661 had stage 1 EC. The rates
      of presumed preoperative type 1 low-, intermediate-, high-risk EC and type 2 EC
      were 310 (46.9 %), 218 (33 %), 39 (5.9 %), and 94 (14.2 %) respectively. Among
      567 type 1 patients, 35 % were upstaged and 6 % were downstaged. Fair agreement
      was found between preoperative and postoperative risk assessment (kappa = 0.37).
      Patients with presumed low- and intermediate-risk EC upstaged postoperatively to
      FIGO stage II/III were more likely to have a restaging operation than patients
      upstaged to type 1 high-risk FIGO stage I EC: 37/70 (52.8 %) versus 26/75 (34.6
      %), p = 0.027. The proportions of patients undergoing the recommended subsequent
      pelvic and/or para-aortic lymph node dissection were low: 34/85 (40 %) and 47/145
      (32.4 %) respectively. Lymph node samplings were mainly performed by laparoscopy:
      31/34 (91.2 %) and 40/47 (85.1 %) for pelvic and para-aortic dissection
      respectively. CONCLUSIONS: Our survey showed that the performance of preoperative
      assessment of FIGO stage I EC was moderate and that adherence to the guidelines
      was low.

PMID- 25605510
TI  - Optimal submucosal invasion of early gastric cancer for endoscopic resection.
AB  - BACKGROUND: A small differentiated gastric cancer with minute submucosal invasion
      after endoscopic resection is regarded as the curative resection criterion of an
      expanded indication. However, recent studies have shown a high incidence of lymph
      node metastasis in those meeting the expanded criteria. The aim of this study was
      to evaluate the validity of the 500 MUm criterion and to determine an optimal
      cutoff value for the expanded indication. METHODS: We reviewed the
      clinicopathological data of 1,322 patients who underwent curative resection for
      submucosal gastric cancer between 2001 and 2013. The full thickness of the
      submucosa and the incidence of lymph node metastasis according to the depth of
      the submucosal invasion were evaluated. The sensitivity, specificity, and
      positive and negative predictive values were calculated with receiver operating
      characteristic (ROC) curve analysis. RESULTS: The mean full thickness of the
      submucosa was 2,605 +/- 1,760 MUm, and the incidence of lymph node metastasis in
      103 tumors meeting the expanded indication was 3.9 % (4/103). In the ROC
      analysis, the area under the curve was 0.664 (95 % confidence interval 0.538
      0.791; p = 0.017), and the highest negative predictive value of 98 % was observed
      when the cutoff value was 300 MUm. CONCLUSIONS: This study suggests that a range
      reduction in the depth of submucosal invasion is required to obtain a high
      negative predictive value. Further large-scale studies are required to validate
      the optimal cutoff value proposed in this study.

PMID- 25605512
TI  - The training and certification of surgical oncologists globally.
AB  - BACKGROUND: The global cancer burden (GCB) is expected to rise significantly
      during the next few decades with most of the new cancers and cancer-related
      deaths afflicting the low- to middle-income countries. The ability to tackle this
      rising GCB requires the presence of an adequately trained surgical oncology
      workforce, which is dependent on credible training pathways and sustainable
      certification pipelines. The purpose of this article is to review briefly the
      training patterns and certification requirements for surgical oncologists
      globally by sampling representative countries across all regions of the world.
      METHODS: A thorough literature search was conducted using multiple websites of
      credible national/global organizations as well as the websites of individual
      countries. Countries from select regions in the world were included (based on the
      World Health Organization regions and Human Development Index) in the analysis to
      determine the prevalent trends in the training of surgical oncologists globally.
      RESULTS: Several trends and significant differences were noted in the training
      patterns of surgical oncologists globally. The presence or absence of domestic
      surgical oncology fellowships had an inverse correlation to the income level of
      the country. Countries without domestic fellowships usually relied on high-income
      foreign destinations for their training. CONCLUSIONS: The results of the analysis
      demonstrated significant variability in training of surgical oncologists
      globally. Despite the diversity, we noticed some general trends based on which
      some recommendations were put forth for increasing the global surgical oncology
      workforce.

PMID- 25605511
TI  - Pattern of Postoperative Mortality After Esophageal Cancer Resection According to
      Center Volume: Results from a Large European Multicenter Study.
AB  - BACKGROUND: High center procedural volume has been shown to reduce postoperative
      mortality (POM); however, the cause of POM has been poorly studied previously.
      The aim of this study was to define the pattern of POM and major morbidity in
      relation to center procedural volume. METHODS: Data from 2,944 consecutive adult
      patients undergoing esophagectomy for esophageal cancer in 30 centers between
      2000 and 2010 were retrospectively collected. Data between patients who suffered
      30-day POM were compared with those who did not. Factors associated with POM were
      identified using binary logistic regression, with propensity matching to compare
      low- (LV) and high-volume (HV) centers. RESULTS: The 30-day and in-hospital POM
      rates were 5.0 and 7.3 %, respectively. Pulmonary complications were the most
      common, affecting 38.1 % of patients, followed by surgical site infection (15.5
      %), cardiovascular complications (11.2 %), and anastomotic leak (10.2 %). Factors
      that were independently associated with 30-day POM included American Society of
      Anesthesiologists grade IV, LV center, anastomotic leak, pulmonary,
      cardiovascular and neurological complications, and R2 resection margin status.
      Surgical complications preceded POM in approximately 30 % of patients compared to
      medically-related causes in 68 %. Propensity-matched analysis demonstrated LV
      centers were significantly associated with increased 30-day POM, and POM
      secondary to anastomotic leak, and pulmonary- and cardiac-related causes.
      CONCLUSIONS: The results of this large, multicenter study provide further
      evidence to support the centralization of esophagectomy to HV centers, with a
      lower rate of morbidity and better infrastructure to deal with complications
      following major surgery preventing further mortality.

PMID- 25605513
TI  - Control of cancer of the cervix in low- and middle-income countries.
AB  - Cervical cancer is the fourth most common cancer among women globally but the
      second most common in Sub-Saharan Africa (SSA). The high burden of cervical
      cancer in developing countries reflects the absence of cervical cancer prevention
      programs. The majority of the incident cases and deaths from cervical cancer,
      greater than 85%, occur in developing countries, where resources for early
      detection and treatment are severely limited. Survival from cancer in Africa is
      very poor due to late presentation and lack of access to effective treatment.
      Radiation, chemotherapy, and surgical oncology are not available in many parts of
      SSA. It is estimated that by 2030 cancer will affect much larger numbers of
      people living in low- and middle-income countries. Very few, if any, are prepared
      for or have sufficient health care infrastructure to provide acceptable services.
      It is imperative that governments in low- and middle-income countries pay urgent
      attention to the problem by developing National Cancer Control Programs, which
      should include population-based registries and data collection systems that allow
      an accurate evaluation of the burden of disease and hence resources required to
      meet it.

PMID- 25605514
TI  - Tumor mitotic rate added to the equation: melanoma prognostic factors changed? :
      a single-institution database study on the prognostic value of tumor mitotic rate
      for sentinel lymph node status and survival of cutaneous melanoma patients.
AB  - BACKGROUND: This study aimed to investigate the predictive value of the tumor
      mitotic rate per mm(2) (TMR) for sentinel lymph node (SLN) status and survival in
      intermediate and thick cutaneous melanoma. METHODS: Patients treated for stage I
      and II melanoma with wide local excision and SLN biopsy between May 1995 and May
      2013 were analyzed. In case of insufficient data regarding TMR, pathology slides
      were reanalyzed. Prognostic factors for SLN status and survival were analyzed
      with the emphasis on TMR, which was analyzed as a continuous variable,
      dichotomized (median value) and categorized by two methods. RESULTS: The study
      analyzed 453 patients with complete TMR data. The median Breslow thickness was
      2.20 mm, and 31.8 % of patients had tumor-positive sentinel lymph node biopsies
      (SLNBs). In the univariate analysis, TMR was associated with tumor-positive SLNB.
      This association was not significant in the multivariate analysis. Breslow
      thickness, primary tumor location on trunk and legs, and younger age were
      associated with tumor-positive SNLB. At a median follow-up of 47 months, 119
      patients (26.3 %) had recurrent disease, and 92 (20.3 %) had died of melanoma. In
      the univariate analysis, TMR could be established as a significant prognostic
      factor for disease-free and disease-specific survival, but not in the
      multivariate analyses. Breslow thickness, ulcerated melanoma, and tumor-positive
      SLNB were significant prognostic factors for survival. CONCLUSION: The study was
      unable to establish TMR as an independent prognostic factor associated with the
      presence of SLN metastasis. Regarding survival, increasing TMR showed a strong
      association with decreased survival in the univariate analysis, but this
      association was rendered nonsignificant by the importance of Breslow thickness
      and ulceration status in the multivariate model.

PMID- 25605515
TI  - Intraoperatively assessed macroscopic serosal changes in patients with curatively
      resected advanced gastric cancer: clinical implications for prognosis and
      peritoneal recurrence.
AB  - BACKGROUND: This study aimed to validate the prognostic relevance of macroscopic
      serosal changes in patients with resected gastric cancer. Prospectively collected
      databases of two multicenter randomized phase III trials of adjuvant chemotherapy
      were analyzed. METHODS: For this study, 655 patients in the control groups of AMC
      0101 and 0201 trials were selected. Macroscopic serosal changes were determined
      according to disruptions in serosal continuity, such as changes in color or
      nodular texture by the operating surgeon. Correlations with recurrence-free
      survival (RFS), overall survival (OS), and time to peritoneal recurrence were
      analyzed. RESULTS: Macroscopic serosal changes were identified intraoperatively
      in 432 patients (66 %) and found to be significantly associated with multifocal
      or diffuse involvement (p = 0.001), Borrmann type 4 (p = 0.005), advanced
      pathologic T (p < 0.001), N (p < 0.001), overall stage (p < 0.001), and total
      gastrectomy (p < 0.001). In multivariate analyses, which included prognostic
      factors of localized gastric cancer, macroscopic serosal changes were
      significantly associated with poor RFS [hazard ratio (HR) 2.0; 95 % confidence
      interval (CI), 1.4-2.7; p < 0.001] and OS (HR 2.1; 95 % CI 1.5-3.0; p < 0.001).
      The changes also were significantly related to shorter time to peritoneal
      recurrence (HR 2.9; 95 % CI 1.7-5.0; p < 0.001). CONCLUSIONS: Intraoperatively
      assessed macroscopic serosal changes confer a poor prognosis and increased
      peritoneal recurrence for patients with curatively resected gastric cancer.
      Macroscopic assessment of serosal changes may be a useful indicator that allows
      better risk stratification of patients with resected gastric cancer in terms of
      prognosis and peritoneal recurrence.

PMID- 25605516
TI  - Totally Laparoscopic Microwave Ablation and Portal Vein Ligation for Staged
      Hepatectomy : A New Minimally Invasive Two-Stage Hepatectomy.
AB  - BACKGROUND: Laparoscopic microwave ablation and portal vein ligation for staged
      hepatectomy (LAPS) is a new technique with a first laparoscopic step available in
      cases of unresectable right liver masses and inadequate future liver remnant
      (FLR). METHODS: In Step 1, laparoscopic right portal vein occlusion is performed
      with microwave ablation on the future transection plane and in the FLR. Step 2
      consists of a totally laparoscopic right trisectionectomy. RESULTS: Duration of
      the Step 1 operation was 170 min, without the need for blood transfusions and
      intensive care unit admission. The postoperative liver volumetric computed
      tomography scan was performed on postoperative day 9 and revealed a satisfactory
      left hepatic hypertrophy (FLR 666 cm(3); FLR to body weight ratio 0.96; FLR
      increase 90.4 %; daily FLR hypertrophy 35 cm(3)/day). Duration of the Step 2
      operation was 630 min (liver transection time 240 min). Blood loss was 700 cc,
      with no need for transfusion. The specimen was extracted through a 10-cm
      Pfannenstiel incision, and pathology revealed a tumor-free resection margin (R0).
      The patient was discharged on postoperative day 7 without complications (total
      hospital stay for Step 1 + Step 2: 10 days). CONCLUSIONS: Totally LAPS is a
      technically feasible and safe procedure. It could provide benefit in selected
      patients with primarily non-resectable liver cancer, making extreme liver surgery
      easy and safe in well-selected patients.

PMID- 25605517
TI  - A prospective 1-year comparative study of endoscopic thyroidectomy via a
      retroauricular approach versus conventional open thyroidectomy at a single
      institution.
AB  - OBJECTIVE: The objective of this study was to evaluate the feasibility and safety
      of performing an endoscopic thyroidectomy (ETE) via a retroauricular approach.
      METHODS: Forty-seven patients who underwent ETE via a retroauricular approach
      were included, and a total of 47 patients who underwent conventional open thyroid
      lobectomy in the same period were analyzed as a control group. All patients
      underwent prospective functional evaluations before the operation and 1 week, and
      1, 3, 6, and 12 months postoperatively using a comprehensive battery of
      functional assessments. RESULTS: The mean total operative time was 152 +/- 48
      min, with a mean endoscopic procedure time of 58 +/- 18 min. One patient
      developed temporary vocal fold paralysis. Although most of the parameters for the
      functional outcome were worse in the ETE group, these differences were transient.
      Subjective worsening on the voice handicap index and dysphagia handicap index
      normalized by 3 months postoperatively. The average pain score on a visual analog
      scale at 1 week after surgery was 2.84, representing a tolerable range of
      discomfort. The mean paresthesia/hyperesthesia score was worse in the ETE group
      than the open surgery group by postoperative month 6; however, these differences
      eventually disappeared. Thirty-six of the 47 patients in the ETE group were
      satisfied or extremely satisfied with the retroauricular incision by 6 months
      after surgery. CONCLUSIONS: ETE via a retroauricular approach is a safe,
      feasible, and cosmetically desirable treatment option, with outcomes comparable
      to conventional open thyroidectomy in the longer term.

PMID- 25605518
TI  - Standard versus extralevator abdominoperineal low rectal cancer excision
      outcomes: a systematic review and meta-analysis.
AB  - BACKGROUND: The extended, extralevator abdominoperineal excision has been
      described with the aim of improving oncological low rectal cancer patient
      outcomes. MATERIALS AND METHODS: A systematic literature review was conducted
      using Medline/PubMed, Embase, Cochrane library, and Ovid for standard and
      extralevator abdominoperineal rectal cancer excision studies between 1995 and
      2013. A total of 1,270 articles were identified and screened, and of these, 58
      reports (1 randomized, 5 case-control and 52 cohort studies) were included for
      the qualitative analysis, and 6 were included for the quantitative analysis. The
      primary endpoints included intraoperative tumor perforation, the circumferential
      resection margin involvement, local recurrence rate, and the perineal wound
      complication rate. The secondary endpoints included the length of postoperative
      hospital stay and quality of life. Comprehensive Rev Men, version 5.2 was used
      for the statistical calculations. RESULTS: A significant difference in the
      circumferential resection margin involvement rate [odds ratio (OR) 2.9; p <
      .001], intraoperative perforation (OR 4.30; p < .001), local recurrence rate (OR
      2.52; p = .02), and length of hospital stay (OR 1.06; p < .001) in favor of the
      extended group was observed. Additionally, the perineal wound complications were
      higher in the extended group (OR 0.62; p = .007). No difference in quality of
      life was observed. CONCLUSIONS: Our analysis confirms the oncological advantages
      of the extended abdominoperineal excision method. Although the perineal wound
      complications were higher, the length of postoperative hospital stay was shorter,
      and quality of life was not inferior to the conventional resection method.

PMID- 25605520
TI  - Zinc complexes exhibiting highly efficient thermally activated delayed
      fluorescence and their application to organic light-emitting diodes.
AB  - Metal complexes emitting thermally activated delayed fluorescence based on intra
      ligand charge transfer and enhanced by metallization were synthesized. Organic
      light-emitting diodes using a thermally stable zinc complex processed by vacuum
      vapor deposition achieved an external quantum efficiency of nearly 20%. 

PMID- 25605519
TI  - C1 inhibitor deficiency: 2014 United Kingdom consensus document.
AB  - C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of
      disabling and potentially life-threatening angioedema. Here we present an updated
      2014 United Kingdom consensus document for the management of C1 inhibitor
      deficient patients, representing a joint venture between the United Kingdom
      Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the
      consensus, we assembled a multi-disciplinary steering group of clinicians, nurses
      and a patient representative. This steering group first met in 2012, developing a
      total of 48 recommendations across 11 themes. The statements were distributed to
      relevant clinicians and a representative group of patients to be scored for
      agreement on a Likert scale. All 48 statements achieved a high degree of
      consensus, indicating strong alignment of opinion. The recommendations have
      evolved significantly since the 2005 document, with particularly notable
      developments including an improved evidence base to guide dosing and indications
      for acute treatment, greater emphasis on home therapy for acute attacks and a
      strong focus on service organization. 

PMID- 25605522
TI  - Suppression of transient receptor potential canonical channel 4 inhibits vascular
      endothelial growth factor-induced retinal neovascularization.
AB  - Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and
      thus contributes to many vasoproliferative retinopathies including retinopathy of
      prematurity. Based on the importance of canonical transient receptor potential
      (TRPC) channels in VEGF signaling, we firstly evaluated the expression of TRPC
      channels in mouse retina by reverse transcriptase-polymerase chain reaction. All
      seven TRPC channels were expressed in mouse retina. TRPC4 channels were chosen
      for further analysis based on their upregulation on hypoxic retina according to
      the GEO database under the identifier GSE19886. Interestingly, TRPC4 suppression
      by intravitreal injection of siRNA against mTRPC4 significantly inhibited retinal
      neovascularization. To further investigate the effect of TRPC4 suppression on
      neovascularization, human retina microvascular endothelial cells (HRMECs) that
      are responsible for initiating neovascularization in response to increased VEGF
      in OIR retina were transfected with siRNA against TRPC4. As we have expected,
      suppression of TRPC4 effectively inhibited VEGF-induced migration and tube
      formation as well. Further evaluation on VEGF signaling pathway by western blot
      analysis of signaling molecules discovered that VEGF-induced activation of ERK,
      p38 MAPK and AKT signaling pathways were inhibited by suppression of TRPC4. These
      findings suggest that suppression of TRPC4 could be an alternative therapeutic
      option for VEGF-induced retinal neovascularization. 

PMID- 25605521
TI  - The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and
      Plasmodium spp.
AB  - Apicomplexan parasites have complex life cycles, frequently split between
      different hosts and reliant on rapid responses as the parasites react to changing
      environmental conditions. Calcium ion (Ca(2+)) signaling is consequently
      essential for the cellular and developmental changes that support Apicomplexan
      parasitism. Apicomplexan genomes reveal a rich repertoire of genes involved in
      calcium signaling, although many of the genes responsible for observed
      physiological changes remain unknown. There is evidence, for example, for the
      presence of a nifedipine-sensitive calcium entry mechanism in Toxoplasma, but the
      molecular components involved in Ca(2+) entry in both Toxoplasma and Plasmodium,
      have not been identified. The major calcium stores are the endoplasmic reticulum
      (ER), the acidocalcisomes, and the plant-like vacuole in Toxoplasma, or the food
      vacuole in Plasmodium spp. Pharmacological evidence suggests that Ca(2+) release
      from intracellular stores may be mediated by inositol 1,4,5-trisphosphate (IP3)
      or cyclic ADP ribose (cADPR) although there is no molecular evidence for the
      presence of receptors for these second messengers in the parasites. Several
      Ca(2+)-ATPases are present in Apicomplexans and a putative mitochondrial
      Ca(2+)/H(+) exchanger has been identified. Apicomplexan genomes contain numerous
      genes encoding Ca(2+)-binding proteins, with the notable expansion of calcium
      dependent protein kinases (CDPKs), whose study has revealed roles in gliding
      motility, microneme secretion, host cell invasion and egress, and parasite
      differentiation. Microneme secretion has also been shown to depend on the C2
      domain containing protein DOC2 in both Plasmodium spp. and Toxoplasma, providing
      further evidence for the complex transduction of Ca(2+) signals in these
      organisms. The characterization of these pathways could lead to the discovery of
      novel drug targets and to a better understanding of the role of Ca(2+) in these
      parasites. 

PMID- 25605523
TI  - The other side of the story - maternal perceptions of safety advice and
      information: a qualitative approach.
AB  - BACKGROUND: A qualitative study of maternal perceptions of home safety advice.
      The aim was to gain an understanding of maternal perceptions of and possible
      barriers to the implementation of home safety advice. METHODS: Semi-structured
      interviews with 37 mothers with a child aged less than 5 years of age; 16 were
      mothers living in an area of socio-economic disadvantage (with a high rate of
      childhood unintentional injury), 21 were mothers living in an area of relative
      affluence (with a low rate of childhood unintentional injury). Thematic analysis
      was used to analyse the data. RESULTS: Although some mothers living in both areas
      found talking to a health professional about child home safety was helpful,
      mothers in both areas tended to find talking to other mothers as being more
      helpful and they preferred this to talking to a professional. Barriers to
      obtaining safety advice from professionals exist for mothers living in both
      areas. Mothers living in the advantaged area describe 'feeling silly' and that
      they should 'know it already' when talking to professionals. Mothers living in
      the disadvantaged area are less likely to access home safety advice due to fear
      of being perceived as an incompetent mother and the fear of social service
      involvement. CONCLUSIONS: Mothers find home safety advice from other parents more
      useful and prefer this to advice from professionals. This suggests greater use
      could be made of appropriately trained parents to deliver safety advice and
      education. Fear and mistrust can limit access to child safety advice in parents
      living in disadvantaged areas and this may be a potential explanation for
      differential unintentional injury rates as those who need the advice and support
      most may be least likely to access it. Further research should explore how
      professionals can build trust, gain parents' confidence and provide child safety
      advice and education that is targeted appropriately to parents living
      circumstances and their child safety needs.

PMID- 25605524
TI  - Atypical presentation of calvarial metastasis of renal cell carcinoma in an
      adolescent: A rare case diagnosed on fine needle aspiration cytology with
      literature review.
AB  - Renal cell carcinoma (RCC) is a complex and challenging neoplasm both in terms of
      treatment as well as diagnosis. Its unpredictable biological behavior and many
      deceptive appearances can sometimes bewilder the pathologist. We hereby report a
      rare case of a 17 year old girl presenting with an occipital swelling and
      importantly no prior documents at the time of aspiration. Fine needle aspiration
      cytology showed features of metastatic carcinoma with the following
      possibilities; metastatic RCC, melanoma, and hepatocellular carcinoma. Further
      detailed history of the patient and investigations were advised. Intraoperative
      squash smears also showed similar features. Histopathology of the lesion showed
      features of metastatic RCC. This case highlights the fact that a skull lesion in
      rare cases may be the presenting sign of an underlying malignancy. In the absence
      of key documents, providing the correct diagnosis may become very challenging and
      cytomorphology alone can be extremely helpful.

PMID- 25605525
TI  - Age group analysis of psychological, physical and functional deterioration in
      patients hospitalized for pneumonia.
AB  - INTRODUCTION: Hospital admissions due to pneumonia range from 1.1 to 4 per 1,000
      patients and this figure increases with age. Hospitalization causes a decline in
      functional status. Physical impairment impedes recovery and constitutes a higher
      risk of disability and mortality in elderly people. The objective of this study
      is to assess the impact of hospital stay in patients with pneumonia related with
      age. METHOD: A total of 116 patients with pneumonia were included in this study,
      and divided into two age groups:<75 years (n=68) and >= 75 years (n=48).
      Respiratory function, physical function and psychological and emotional profile
      were evaluated. Pneumonia severity, nutritional status, independence and
      comorbidities were also assessed. RESULTS: Statistical analyses revealed
      significant differences between both age groups in pneumonia severity and
      comorbidities. Significant improvements between admission and discharge were
      found in lung function in both groups (p<0.05), while a significant decrease
      (p<0.05) in strength assessed by dynamometer was found in the >=75 years group.
      CONCLUSION: Hospitalization leads to a significant physical impairment in
      patients admitted for pneumonia. This deterioration increases with age.

PMID- 25605526
TI  - Pulmonary thromboendarterectomy in 106 patients with chronic thromboembolic
      pulmonary hypertension.
AB  - INTRODUCTION: Pulmonary thromboendarterectomy is the treatment of choice in
      chronic thromboembolic pulmonary hypertension. We report our experience with this
      technique. METHODS: Between February 1996 and June 2014, we performed 106
      pulmonary thromboendarterectomies. Patient population, morbidity and mortality
      and the long-term results of this technique (survival, functional improvement and
      resolution of pulmonary hypertension) are described. RESULTS: Subjects' mean age
      was 53+/-14 years. A total of 89% were WHO functional class III-IV, presurgery
      mean pulmonary pressure was 49+/-13mmHg and mean pulmonary vascular resistance
      was 831+/-364 dynes.s.cm(-5). In-hospital mortality was 6.6%. The most important
      post-operative morbidity was reperfusion pulmonary injury, in 20% of patients;
      this was an independent risk factor (p=0.015) for hospital mortality. With a 31
      month median follow-up (interquartile range: 50), 3- and 5-year survival was 90
      and 84%. At 1 year, 91% were WHO functional class I-II; mean pulmonary pressure
      (27+/-11mmHg) and pulmonary vascular resistance (275+/-218 dynes.s.cm(-5)) were
      significantly lower (p<0.05) than before the intervention. Although residual
      pulmonary hypertension was detected in 14 patients, their survival at 3 and 5
      years was 91 and 73%, respectively. CONCLUSIONS: Pulmonary thromboendarterectomy
      offers excellent results in chronic thromboembolic pulmonary hypertension. Long
      term survival is good, functional capacity improves, and pulmonary hypertension
      is resolved in most patients.

PMID- 25605527
TI  - The prevalence of Hymenoptera venom allergy in adults: the results of a very
      crowded city in Euroasia.
AB  - BACKGROUND: There are scarce data about the prevalence of Hymenoptera venom
      allergy in the general population. The aim of this study was to determine the
      prevalence of Hymenoptera venom allergy in the general adult population of
      Istanbul. METHODS: A total of 17,064 randomly selected telephone numbers were
      contacted and 11,816 (69.25%) individuals who agreed to participate completed a
      questionnaire. Those who disclosed hypersensitivity reactions due to Hymenoptera
      stings in this initial survey were called again and given another questionnaire.
      Those who were suspected of experiencing hypersensitivity reactions to
      Hymenoptera stings were invited for a clinical investigation with in vivo and in
      vitro diagnostic tests. RESULTS: According to the first questionnaire, a total of
      1171 (9.9%; 95% CI: 9.38-10.47%) were suspected of having a hypersensitivity to
      Hymenoptera stings. 51.75% (n: 606) answered the second questionnaire and 21% (n:
      128) of these were still suspected of having a hypersensitivity to Hymenoptera
      stings (1.1%; 95% CI: 0.9-1.29%). The confirmed prevalence of hypersensitivity to
      Hymenoptera stings according to skin tests and in vitro sIgE levels was 0.2% (95%
      CI: 0.14-0.30%). Nearly all of the participants with systemic reactions were
      admitted to the emergency department, although only one tenth of them received
      adrenaline in the emergency room. 2.3% carried an adrenaline injector, whereas
      none of the patients received venom immunotherapy. CONCLUSIONS: The prevalence of
      Hymenoptera sting reactions in our geographical region is comparable with other
      European studies. There is a need to increase the awareness of adrenaline in the
      emergency management of insect sting anaphylaxis and venom immunotherapy in the
      prophylaxis.

PMID- 25605529
TI  - Oxidized dietary oils enhance immediate- and/or delayed-type allergic reactions
      in BALB/c mice.
AB  - BACKGROUND: The consumption of cooking oils may exacerbate some allergic
      diseases. In the present study, the effects of naturally oxidized olive oil on
      immediate- and/or delayed-type allergic reactions were investigated in BALB/c
      mice. METHODS: Mouse models of 3 types of allergic reactions: contact
      hypersensitivity (CHS), active cutaneous anaphylaxis (ACA), and DNFB-induced
      hypersensitivity, were orally administered naturally oxidized olive oil that was
      obtained by keeping the oil at room temperature for more than 3 years. The
      effects of ultraviolet ray (UV)-irradiated olive oil and other dietary oils as
      well as their possible oxidation products on CHS were also investigated. RESULTS:
      Naturally oxidized olive oil had a high peroxide value (POV) and exacerbated CHS,
      ACA, and DNFB-induced hypersensitivity in a POV-dependent manner. UV-irradiated
      olive oil, corn oil, sesame oil and triolein had high POVs, but almost the same
      acid value (AV) and thiobarbituric acid-reactive substance (TBARS) level as fresh
      oils. Fresh olive oil and the representative oxidation product with a high AV or
      TBARS level had no effect on CHS, whereas all UV-irradiated oils and naturally
      oxidized olive oil exacerbated it. CONCLUSIONS: Oxidized dietary oils that have
      high POVs exacerbated immediate- and/or delayed-type allergic reactions
      regardless of the different oil constituents or oxidation processes.

PMID- 25605528
TI  - Immunological parameters in prophylactic sublingual immunotherapy in asymptomatic
      subjects sensitized to Japanese cedar pollen.
AB  - BACKGROUND: This study aims to examine the immunological parameters, focusing IL
      10 productivity, in prophylactic sublingual immunotherapy (SLIT) in asymptomatic
      subjects sensitized to Japanese cedar pollen (JCP). METHODS: This study was
      conducted as part of a randomized, double-blind, placebo-controlled, multiple
      center trial, and was performed for two consecutive pollen seasons in 2012 and
      2013. The present results were based only on our institution. We recruited 29
      participants with specific IgE against JCP of at class 2 and higher levels
      without history of the pollinosis symptoms at the time of JCP scattering. The
      SLIT group received standardized JCP extract for five months over the pollen
      season. We observed and judged development of the symptoms in the pollen season.
      The percentage of IL-10 producing CD4(+) T (Trl) cells, B cells and monocytes
      were analyzed by flow cytometry. JCP specific IgE and total IgE were also
      measured. RESULTS: The ratio of development of cedar pollinosis was significantly
      lower in the SLIT group compared to the placebo group in 2013. In 2012, the
      percentage of circulating Tr1 cells and IL-10 producing monocytes significantly
      increased in the SLIT group. In 2013, the percentage of circulating Tr1 cells and
      IL-10 producing B cells increased significantly in the SLIT group. The percentage
      of circulating IL-10 producing monocytes significantly decreased in the placebo
      group. CONCLUSIONS: Prophylactic SLIT is effective for prevention of the
      development of pollinosis. Induction of IL-10 producing T cells, B cells and
      monocytes is an important mechanism of SLIT for prevention of pollinosis in
      asymptomatic but sensitized subjects.

PMID- 25605530
TI  - Real-world effect of gastroesophageal reflux disease on cough-related quality of
      life and disease status in asthma and COPD.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common
      causes of chronic cough and often coexists with asthma or chronic obstructive
      pulmonary disease (COPD); however, it is unknown whether there are differences in
      the effect of GERD on these diseases. The purpose of this study was to assess the
      difference in the effect of GERD on cough-related quality of life and disease
      status in asthma and COPD in a real-world setting. METHODS: Subjects were 132
      patients with overall controlled asthma and 102 patients with stable COPD. They
      completed the frequency scale for symptoms of GERD (FSSG), a validated Japanese
      questionnaire for GERD, the Leicester Cough Questionnaire (LCQ), and the Asthma
      Control Test (ACT) or COPD assessment test (CAT) questionnaires. RESULTS: We
      found that 29 (22.0%) patients with asthma and 22 (21.6%) patients with COPD had
      GERD. There was no difference in the FSSG scale between the diseases. The
      patients with GERD, regardless of having asthma or COPD, had lower LCQ scores
      affecting all health domains and lower ACT or higher CAT scores than those
      without GERD. Overall, the patients with COPD had lower LCQ scores regardless of
      the presence or absence of GERD. The FSSG scale was negatively correlated with
      the LCQ total score in asthma and in COPD. In contrast, the FSSG scale was
      positively correlated with the CAT score but not with the ACT score. CONCLUSIONS:
      Patients with GERD had impaired cough-related quality of life, poor asthma
      control or more symptoms and impacts of COPD.

PMID- 25605532
TI  - Capsule commentary on Mosher et al., Trends in prevalent and incident opioid
      receipt: an observational study in Veterans Health Administration 2004-2012.

PMID- 25605534
TI  - Synthesis of polycyclic tertiary carbinamines by samarium diiodide mediated
      cyclizations of indolyl sulfinyl imines.
AB  - Samarium diiodide mediated cyclizations of N-acylated indole derivatives bearing
      sulfinyl imine moieties afforded polycyclic tertiary carbinamines with moderate
      to excellent diastereoselectivities. Lithium bromide and water turned out to be
      the best additives to achieve these transformations in good yields. Using
      enantiopure sulfinyl imines the outcome strongly depends on the reactivity of the
      indole moiety. Whereas with unactivated indole derivatives desulfinylation and
      formation of racemic products was observed, indoles bearing electron-withdrawing
      substituents at C-3 afforded the polycyclic products with intact N-sulfinyl
      groups and with excellent diastereoselectivity, finally allowing the preparation
      of enantiopure tertiary carbinamines. The mechanisms of these processes are
      discussed. 

PMID- 25605531
TI  - Rates and correlates of potentially inappropriate colorectal cancer screening in
      the Veterans Health Administration.
AB  - BACKGROUND: Inappropriate use of colorectal cancer (CRC) screening procedures can
      inflate healthcare costs and increase medical risk. Little is known about the
      prevalence or causes of inappropriate CRC screening. OBJECTIVE: Our aim was to
      estimate the prevalence of potentially inappropriate CRC screening, and its
      association with patient and facility characteristics in the Veterans Health
      Administration (VHA) . DESIGN AND PARTICIPANTS: We conducted a cross-sectional
      study of all VHA patients aged 50 years and older who completed a fecal occult
      blood test (FOBT) or a screening colonoscopy between 1 October 2009 and 31
      December 2011 (n = 1,083,965). MAIN MEASURES: Measures included: proportion of
      patients whose test was classified as potentially inappropriate; associations
      between potentially inappropriate screening and patient demographic and health
      characteristics, facility complexity, CRC screening rates, dependence on FOBT,
      and CRC clinical reminder attributes. KEY RESULTS: Of 901,292 FOBT cases, 26.1 %
      were potentially inappropriate (13.9 % not due, 7.8 % limited life expectancy,
      11.0 % receiving FOBT when colonoscopy was indicated). Of 134,335 screening
      colonoscopies, 14.2 % were potentially inappropriate (10.4 % not due, 4.4 %
      limited life expectancy). Each additional 10 years of patient age was associated
      with an increased likelihood of undergoing potentially inappropriate screening
      (ORs = 1.60 to 1.83 depending on screening mode). Compared to facilities scoring
      in the bottom third on a measure of reliance on FOBT (versus screening
      colonoscopy), facilities scoring in the top third were less likely to conduct
      potentially inappropriate FOBTs (OR = 0.,78) but more likely to conduct
      potentially inappropriate colonoscopies (OR = 2.20). Potentially inappropriate
      colonoscopies were less likely to be conducted at facilities where primary care
      providers were assigned partial responsibility (OR = 0.74) or full responsibility
      (OR = 0.73) for completing the CRC clinical reminder. CONCLUSIONS: A substantial
      number of VHA CRC screening tests are potentially inappropriate. Establishing
      processes that enforce appropriate screening intervals, triage patients with
      limited life expectancies, and discourage the use of FOBTs when a colonoscopy is
      indicated may reduce inappropriate testing.

PMID- 25605533
TI  - Risk for Tuberculosis Disease Among Contacts with Prior Positive Tuberculin Skin
      Test: A retrospective Cohort Study, New York City.
AB  - BACKGROUND: Patients with prior positive tuberculin skin test (TST) results may
      benefit from prophylaxis after repeat exposure to infectious tuberculosis (TB).
      OBJECTIVE: To evaluate factors associated with active TB disease among persons
      with prior positive TST results named as contacts of persons with infectious TB.
      DESIGN: Population-based retrospective cohort study. PARTICIPANTS: A total of
      2,933 contacts with prior positive TST results recently exposed to infectious TB
      identified in New York City's TB registry during the period from January 1, 1997
      through December 31, 2003. MAIN MEASUREMENTS: Contacts developing active TB
      disease <= 4 years after exposure were identified and compared with those who did
      not, using Poisson regression analysis. Genotyping was performed on selected
      Mycobacterium tuberculosis-positive isolates. KEY RESULTS: Among contacts with
      prior positive TST results, 39 (1.3 %) developed active TB disease <= 4 years
      after exposure (<= 2 years: 34). Risk factors for contacts that were
      independently associated with TB were age < 5 years (adjusted prevalence ratio
      [aPR] = 19.48; 95 % confidence interval [CI] = 7.15-53.09), household exposure
      (aPR = 2.60;CI = 1.30-5.21), exposure to infectious patients (i.e., cavities on
      chest radiograph, acid-fast bacilli on sputum smear; aPR = 1.9 3; CI = 1.01
      3.71), and exposure to a U.S.-born index patient (aPR = 4.04; CI = 1.95-8.38).
      Receipt of more than 1 month of treatment for latent TB infection following the
      current contact investigation was found to be protective (aPR = 0.27; CI =  .08
      0.93). Genotype results were concordant with the index patients among 14 of 15
      contacts who developed active TB disease and had genotyping results available.
      CONCLUSIONS: Concordant genotype results and a high proportion of contacts
      developing active TB disease within 2 years of exposure indicate that those with
      prior positive TST results likely developed active TB disease from recent rather
      than remote infection. Healthcare providers should consider prophylaxis for
      contacts with prior TB infection, especially young children and close contacts of
      TB patients (e.g., those with household exposure).

PMID- 25605535
TI  - Effect of equipment dead space on multiple breath washout measures.
AB  - BACKGROUND AND OBJECTIVE: Multiple breath inert gas washout (MBW) systems are
      designed to minimize equipment dead space volume (Vd). Animal and infant studies
      have demonstrated the impact of increased Vd on MBW measurements. In this study,
      we investigate the effect of Vd of a nitrogen (N2 ) MBW system on MBW
      measurements in preschool children. METHODS: N2 MBW measurements were performed
      in healthy adults under standard conditions; Vd was added to match the
      relationship between Vd and lung volumes observed in preschool children.
      Subsequently, subjects were measured on a sulfur hexafluoride (SF6 ) MBW system
      under standard conditions and with Vd added to match that of the N2 MBW system.
      Healthy preschool children and children with cystic fibrosis were tested on both
      the N2 MBW and SF6 MBW in random order on the same day. A correction equation was
      derived based on the adult experiments and tested on the preschool data. RESULTS:
      Increasing the Vd of the N2 MBW system resulted in a higher lung clearance index
      (LCI). A strong non-linear relationship between N2 LCI and the Vd/tidal volume
      was observed. When the Vd was equivalent between systems, LCI measured by the SF6
      MBW system was similar to that measured by the N2 MBW. LCI was higher on the N2
      MBW than the SF6 MBW in preschool children. Correcting for the equipment Vd of
      the N2 MBW resulted in better agreement. CONCLUSIONS: Equipment Vd affects LCI
      measurements especially in young children where Vd is large relative to lung
      volumes.

PMID- 25605536
TI  - Structure of dimeric, recombinant Sulfolobus solfataricus phosphoribosyl
      diphosphate synthase: a bent dimer defining the adenine specificity of the
      substrate ATP.
AB  - The enzyme 5-phosphoribosyl-1-alpha-diphosphate (PRPP) synthase (EC 2.7.6.1)
      catalyses the Mg(2+)-dependent transfer of a diphosphoryl group from ATP to the
      C1 hydroxyl group of ribose 5-phosphate resulting in the production of PRPP and
      AMP. A nucleotide sequence specifying Sulfolobus solfataricus PRPP synthase was
      synthesised in vitro with optimised codon usage for expression in Escherichia
      coli. Following expression of the gene in E. coli PRPP synthase was purified by
      heat treatment and ammonium sulphate precipitation and the structure of S.
      solfataricus PRPP synthase was determined at 2.8 A resolution. A bent dimer
      oligomerisation was revealed, which seems to be an abundant feature among PRPP
      synthases for defining the adenine specificity of the substrate ATP. Molecular
      replacement was used to determine the S. solfataricus PRPP synthase structure
      with a monomer subunit of Methanocaldococcus jannaschii PRPP synthase as a search
      model. The two amino acid sequences share 35 % identity. The resulting asymmetric
      unit consists of three separated dimers. The protein was co-crystallised in the
      presence of AMP and ribose 5-phosphate, but in the electron density map of the
      active site only AMP and a sulphate ion were observed. Sulphate ion, reminiscent
      of the ammonium sulphate precipitation step of the purification, seems to bind
      tightly and, therefore, presumably occupies and blocks the ribose 5-phosphate
      binding site. The activity of S. solfataricus PRPP synthase is independent of
      phosphate ion.

PMID- 25605537
TI  - Comparison of the microbial communities of hot springs waters and the microbial
      biofilms in the acidic geothermal area of Copahue (Neuquen, Argentina).
AB  - Copahue is a natural geothermal field (Neuquen province, Argentina) dominated by
      the Copahue volcano. As a consequence of the sustained volcanic activity, Copahue
      presents many acidic pools, hot springs and solfataras with different temperature
      and pH conditions that influence their microbial diversity. The occurrence of
      microbial biofilms was observed on the surrounding rocks and the borders of the
      ponds, where water movements and thermal activity are less intense. Microbial
      biofilms are particular ecological niches within geothermal environments; they
      present different geochemical conditions from that found in the water of the
      ponds and hot springs which is reflected in different microbial community
      structure. The aim of this study is to compare microbial community diversity in
      the water of ponds and hot springs and in microbial biofilms in the Copahue
      geothermal field, with particular emphasis on Cyanobacteria and other
      photosynthetic species that have not been detected before in Copahue. In this
      study, we report the presence of Cyanobacteria, Chloroflexi and chloroplasts of
      eukaryotes in the microbial biofilms not detected in the water of the ponds. On
      the other hand, acidophilic bacteria, the predominant species in the water of
      moderate temperature ponds, are almost absent in the microbial biofilms in spite
      of having in some cases similar temperature conditions. Species affiliated with
      Sulfolobales in the Archaea domain are the predominant microorganism in high
      temperature ponds and were also detected in the microbial biofilms. 

PMID- 25605538
TI  - UDP-sulfoquinovose formation by Sulfolobus acidocaldarius.
AB  - The UDP-sulfoquinovose synthase Agl3 from Sulfolobus acidocaldarius converts UDP
      D-glucose and sulfite to UDP-sulfoquinovose, the activated form of sulfoquinovose
      required for its incorporation into glycoconjugates. Based on the amino acid
      sequence, Agl3 belongs to the short-chain dehydrogenase/reductase enzyme
      superfamily, together with SQD1 from Arabidopsis thaliana, the only UDP
      sulfoquinovose synthase with known crystal structure. By comparison of sequence
      and structure of Agl3 and SQD1, putative catalytic amino acids of Agl3 were
      selected for mutational analysis. The obtained data suggest for Agl3 a modified
      dehydratase reaction mechanism. We propose that in vitro biosynthesis of UDP
      sulfoquinovose occurs through an NAD(+)-dependent
      oxidation/dehydration/enolization/sulfite addition process. In the absence of a
      sulfur donor, UDP-D-glucose is converted via UDP-4-keto-D-glucose to UDP-D
      glucose-5,6-ene, the structure of which was determined by (1)H and (13)C-NMR
      spectroscopy. During the redox reaction the cofactor remains tightly bound to
      Agl3 and participates in the reaction in a concentration-dependent manner. For
      the first time, the rapid initial electron transfer between UDP-D-glucose and
      NAD(+) could be monitored in a UDP-sulfoquinovose synthase. Deuterium labeling
      confirmed that dehydration of UDP-D-glucose occurs only from the enol form of UDP
      4-keto-glucose. The obtained functional data are compared with those from other
      UDP-sulfoquinovose synthases. A divergent evolution of Agl3 from S.
      acidocaldarius is suggested. 

PMID- 25605540
TI  - Synthesis of colloidal Janus nanoparticles by asymmetric capping of mesoporous
      silica with phenylsilsesquioxane.
AB  - Colloidal mesoporous silica nanoparticles asymmetrically capped with non-porous
      phenylsilsesquioxane have been prepared by adding phenyltriethoxysilane to an
      aqueous dispersion of mesostructured silica-surfactant composite nanoparticles.
      The integration of colloidal stability, mesoporosity and the Janus structure is
      quite promising for materials design applicable in various fields, including
      catalysis, biomedicine and coatings. 

PMID- 25605539
TI  - Rare event counting of CD59- red cells in human blood: A 47-month experience
      using PNH consensus guidelines for WBC and RBC testing in a reference lab.
AB  - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired
      disorder characterized by increased complement-mediated lysis of erythrocytes
      (RBCs) because of low/absent glycophosphatidylinositol (GPI) anchors of numerous
      cell surface proteins. METHODS: Rare event analysis was applied to 120 million
      RBCs (12 normal individuals) and 102 million RBCs (102 normal individuals) to
      establish a reference range and verify a methodology for rare event analysis.
      Patient PNH testing (n = 10,984) was performed over 47 months using the 2010
      consensus guidelines with CD59-PE and glycophorin A-FITC for RBCs and FLAER-Alexa
      488, CD33-PerCP-Cy5.5, CD15-APC, CD14-APC-Cy7, and CD24-PE for WBCs. RESULTS: The
      distribution of CD59- RBCs in the normal population was asymmetric with a mean of
      5.9, median between 3 and 4, and mode of 2 per million RBCs. The normal range of
      CD59- RBCs was 0-17/million RBCs. A natural cutoff of 2.5% of the peak expression
      of CD59 delineates CD59+ from CD59- populations. The incidence of GPI- samples
      received by the laboratory was 6-7% without correlation to age (P = 0.35) or sex
      (P = 0.45). The percentage of GPI- neutrophils and monocytes were strongly
      correlated (R(2) = 0.96) and usually greater than the percentage of GPI- RBCs.
      CONCLUSION: PNH RBC testing is a good example of rare event analysis applied to
      clinical cytometry-only 2.5 min are required to collect 1 million RBCs. With an
      established normal range of CD59- RBCs, the correlation between total cell count
      and sensitivity for detecting an abnormal population can be calculated using
      Poisson statistics.

PMID- 25605541
TI  - Allogeneic hematopoietic stem cell transplantation for adult patients with mixed
      phenotype acute leukemia: results of a matched-pair analysis.
AB  - Adult patients with mixed phenotype acute leukemia (MPAL) have a poor prognosis,
      and the therapeutic role of allogeneic stem cell transplantation (allo-SCT) for
      MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of
      allo-SCT for MPAL. Eighteen patients with MPAL were identified from the
      transplant outcome database of Kanto Study Group for Cell Therapy (KSGCT). We
      also selected 215 patients with acute myeloid leukemia (AML) and acute
      lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method.
      The 5-yr overall survival (OS) rate of patients with MPAL was 48.1%, and patients
      in remission at the time of transplant showed significantly better survival than
      those not in remission (5-yr OS: 71.8% vs. 0%, P = 0.001). No significant
      differences were seen in OS when stratifying patients according to
      immunophenotype, cytogenetic abnormalities, or the type of induction therapy. The
      5-yr OS rate of patients with MPAL was not significantly different compared with
      AML control patients (48.1% vs. 48.1%; P = 0.855) or ALL control patients (48.1%
      vs. 37.8%; P = 0.426). These results suggested that allo-SCT is an effective
      treatment for MPAL, especially early in the disease course, and innovative
      transplant approaches are warranted to improve the transplant outcome of patients
      with MPAL who are not in remission.

PMID- 25605542
TI  - Differentiating os acromiale from normally developing acromial ossification
      centers using magnetic resonance imaging.
AB  - OBJECTIVE: Acromial fusion may not be complete until age 18-25, making it
      questionable to diagnose os acromiale in adolescents. Os acromiale may exist in
      adolescents and can be differentiated from a developing acromial ossification
      center based on MRI findings. MATERIALS AND METHODS: A total of 128 MRIs of the
      shoulder were randomly and blindly reviewed retrospectively by two
      musculoskeletal radiologists. The MRIs consisted of two groups: (1) 56 of os
      acromiale in adults (25-74 years old, mean, 50) and (2) 72 consecutive of
      adolescents (12-17 years old, mean, 14.5). The following were assessed at the
      interface between the distal acromion and os acromiale/developing ossification
      center(s): presence of os acromiale vs. developing acromion, orientation,
      margins, and edema within and adjacent to it. RESULTS: Fifty-one adults and 49
      adolescents were included. Exclusions were due to poor image quality or
      confounding findings (n = 7) or complete acromial fusion (n = 21 adolescents).
      Utilizing accepted definitions of os acromiale, all adult cases (100 %) were
      accurately diagnosed as os acromiale, with transverse interface orientation and
      irregular margins (94 %, R = 0.86, p < 0.00001). Forty-five (92 %) adolescent
      cases were accurately diagnosed as normally developing acromion with arched
      interface and lobulated margins (92 %, R = 0.92, p < 0.000001). Four (8 %)
      adolescent cases were diagnosed as having os acromiale, with transverse
      orientation and irregular margins. Thirty-five (69 %) and 46 (90 %) adults had
      marrow and interface edema, respectively. Six (12 %) and eight (16 %) adolescents
      had marrow and interface edema, respectively, including the four concluded to be
      os acromiale. CONCLUSIONS: Adolescents may have imaging findings consistent with
      os acromiale. The diagnosis of os acromiale should be based on imaging features
      and not limited by age.

PMID- 25605543
TI  - Venous oxygen saturation is reduced and variable in central retinal vein
      occlusion.

PMID- 25605544
TI  - A double-blind, placebo-controlled trial of adding erythropoietin to intravenous
      methylprednisolone for the treatment of unilateral acute optic neuritis of
      unknown or demyelinative origin.
AB  - PURPOSE: To compare the effect of adding recombinant human erythropoietin (rhEPO)
      to intravenous methylprednisolone for the treatment of unilateral acute optic
      neuritis of unknown or demyelinative origin on the logarithm of the minimum angle
      of resolution (logMAR), perimetric variables [mean deviation (MD) and pattern
      standard deviation (PSD)], and retinal nerve fiber layer (RNFL) thickness in
      optical coherence tomography (OCT). METHODS: Thirty patients (15 patients in each
      group) diagnosed with unilateral acute optic neuritis of unknown or demyelinative
      origin were included. All patients received 1, 000 mg intravenous
      methylprednisolone per day for 3 days. One intravenous bullous dose of rhEPO with
      the dose of 33,000 IU was administered at days 1-3 for the patients in group 2.
      One intravenous bullous dose of 0.9 % normal saline was administered at days 1-3
      for group 1 patients. At 6 months post-intervention, in the involved eye, logMAR,
      MD, PSD, and mean RNFL thickness in each of four quadrants and post-intervention
      changes in each of the variables were compared between group 1 and group 2.
      RESULTS: The amount of MD improvement after the intervention (difference of pre-
      and post-intervention MDs) was significantly higher in the group 2 patients (p =
      0.04). The other post-intervention variables, including post-intervention PSD,
      amount of PSD improvement, and total and four-quadrant post-intervention RNFL
      thickness and RNFL loss (difference of pre- and post-intervention RNFL
      thicknesses), demonstrated no significant differences between group 1 and group
      2. CONCLUSION: Until more controlled studies are available, the rhEPO is not
      recommended as an add-on treatment for optic neuritis.

PMID- 25605545
TI  - Acquired adenoma of the nonpigmented ciliary epithelium: analysis of five cases.
AB  - PURPOSE: Adenoma of the non-pigmented ciliary epithelium (ANPCE) is extremely
      rare. The aim of this study is to present our experience in treating this rare
      entity and to determine the long-term surgical outcomes of local tumor resection
      (partial iridocyclectomy with lamellar sclerouvectomy) in five cases of ANPCE in
      China. PATIENTS AND METHODS: The medical data of four women and one man ranging
      in age from 28 to 46 years (median, 38 years) with ANPCE were reviewed
      retrospectively at the Zhongshan Ophthalmic Center of Sun Yat-sen University,
      China. All patients had received local tumor resection and the diagnosis was
      confirmed by histopathological examination. RESULTS: All five cases experienced
      blurred vision. The right eye was affected in four cases and the left in one.
      Slit-lamp biomicroscopy revealed a nodular, non-pigmented, gray-white mass with a
      slightly irregular surface. Tumor invasion through the peripheral iris was
      observed in two patients, two patients had multiple iris or ciliary cysts, and
      one patient had a partially bloodstained cornea. All tumors transmitted light
      readily. Ultrasound biomicroscopy showed a middle- or hyper-echoic solid mass in
      the ciliary body. MRI examination showed the tumor hyperintense to vitreous on
      T1WI and hypointense to vitreous on T2WI. Local resection was performed in all
      cases. After a median of 5.0 years of follow-up, no tumor recurrence was present
      in any of the cases and all involved eyes were saved. The visual acuity improved
      seven lines in three cases, decreased one line in one case, and vision was lost
      in one case. CONCLUSIONS: ANPCE often presents in adults as gray-white in color,
      with an irregular and sometimes multilobulated surface. The tumor transmits light
      well. Local resection of the mass generally provides the patient with useful
      vision. Recurrence after surgical removal is unlikely.

PMID- 25605546
TI  - Are Australasian Genetic Counselors Interested in Private Practice at the Primary
      Care Level of Health Service?
AB  - This study explored the perceived interest in development of private genetic
      counseling services in collaboration with primary care physicians in the
      Australasian setting by online survey of members of the Australasian Society of
      Genetic Counselors. Four hypothetical private practice models of professional
      collaboration between genetic counselors and primary care physicians or clinical
      geneticists were proposed to gauge interest and enthusiasm of ASGC members for
      this type of professional development. Perceived barriers and facilitators were
      also evaluated. 78 completed responses were included for analysis. The majority
      of participants (84.6 %) showed a positive degree of interest and enthusiasm
      towards potential for clinical work in private practice. All proposed practice
      models yielded a positive degree of interest from participants. Model 4 (the only
      model of collaboration with a clinical geneticist rather than primary care
      physician) was the clearly preferred option (mean = 4.26/5), followed by Model 2
      (collaboration with a single primary care practice) (mean = 4.09/5), Model 3
      (collaboration with multiple primary care clinics, multidisciplinary clinic or
      specialty clinic) (mean = 3.77/5) and finally, Model 1 (mean = 3.61/5), which was
      the most independent model of practice. When participants ranked the options in
      the order of preference, Model 4 remained the most popular first preference (44.6
      %), followed by model 2 (21.6 %), model 3 (18.9 %) and model 1 was again least
      popular (10.8 %). There was no significant statistical correlation between
      demographic characteristics (age bracket, years of work experience, current level
      of work autonomy) and participants' preference for private practice models.
      Support from clinical genetics colleagues and the professional society was highly
      rated as a facilitator and, conversely, lack of such support as a significant
      barrier.

PMID- 25605548
TI  - Tough photoluminescent hydrogels doped with lanthanide.
AB  - Photoluminescent hydrogels have emerged as novel soft materials with potential
      applications in many fields. Although many photoluminescent hydrogels have been
      fabricated, their scope of usage has been severely limited by their poor
      mechanical performance. Here, a facile strategy is reported for preparing
      lanthanide (Ln)-alginate/polyacrylamide (PAAm) hydrogels with both high toughness
      and photoluminescence, which has been achieved by doping Ln(3+) ions (Ln = Eu,
      Tb, Eu/Tb) into alginate/PAAm hydrogel networks, where Ln(3+) ions serve as both
      photoluminescent emitters and physical cross-linkers. The resulting hydrogels
      exhibit versatile advantages including excellent mechanical properties (~ MPa
      strength, ~ 20 tensile strains, ~ 10(4) kJ m(-3) energy dissipation), good
      photoluminescent performance, tunable emission color, excellent processability,
      and cytocompatibility. The developed tough photoluminescent hydrogels hold great
      promises for expanding the usage scope of hydrogels.

PMID- 25605547
TI  - Inhibitory and excitatory neuromodulation by hydrogen peroxide: translating
      energetics to information.
AB  - Historically, brain neurochemicals have been broadly classified as energetic or
      informational. However, increasing evidence implicates metabolic substrates and
      byproducts as signalling agents, which blurs the boundary between energy and
      information, and suggests the introduction of a new category for 'translational'
      substances that convey changes in energy state to information. One intriguing
      example is hydrogen peroxide (H2 O2 ), which is a small, readily diffusible
      molecule. Produced during mitochondrial respiration, this reactive oxygen
      species, can mediate dynamic regulation of neuronal activity and transmitter
      release by activating inhibitory ATP-sensitive K(+) (KATP ) channels, as well as
      a class of excitatory non-selective cation channels, TRPM2. Studies using ex vivo
      guinea pig brain slices have revealed that activity-generated H2 O2 can act via
      KATP channels to inhibit dopamine release in dorsal striatum and dopamine neuron
      activity in the substantia nigra pars compacta. In sharp contrast, endogenously
      generated H2 O2 enhances the excitability of GABAergic projection neurons in the
      dorsal striatum and substantia nigra pars reticulata by activating TRPM2
      channels. These studies suggest that the balance of excitation vs. inhibition
      produced in a given cell by metabolically generated H2 O2 will be dictated by the
      relative abundance of H2 O2 -sensitive ion channel targets that receive this
      translational signal. 

PMID- 25605549
TI  - Acute exposure to silica nanoparticles enhances mortality and increases lung
      permeability in a mouse model of Pseudomonas aeruginosa pneumonia.
AB  - BACKGROUND: The lung epithelium constitutes the first barrier against invading
      pathogens and also a major surface potentially exposed to nanoparticles. In order
      to ensure and preserve lung epithelial barrier function, the alveolar compartment
      possesses local defence mechanisms that are able to control bacterial infection.
      For instance, alveolar macrophages are professional phagocytic cells that engulf
      bacteria and environmental contaminants (including nanoparticles) and secrete pro
      inflammatory cytokines to effectively eliminate the invading
      bacteria/contaminants. The consequences of nanoparticle exposure in the context
      of lung infection have not been studied in detail. Previous reports have shown
      that sequential lung exposure to nanoparticles and bacteria may impair bacterial
      clearance resulting in increased lung bacterial loads, associated with a
      reduction in the phagocytic capacity of alveolar macrophages. RESULTS: Here we
      have studied the consequences of SiO2 nanoparticle exposure on Pseudomonas
      aeruginosa clearance, Pseudomonas aeruginosa-induced inflammation and lung injury
      in a mouse model of acute pneumonia. We observed that pre-exposure to SiO2
      nanoparticles increased mice susceptibility to lethal pneumonia but did not
      modify lung clearance of a bioluminescent Pseudomonas aeruginosa strain.
      Furthermore, internalisation of SiO2 nanoparticles by primary alveolar
      macrophages did not reduce the capacity of the cells to clear Pseudomonas
      aeruginosa. In our murine model, SiO2 nanoparticle pre-exposure preferentially
      enhanced Pseudomonas aeruginosa-induced lung permeability (the latter assessed by
      the measurement of alveolar albumin and IgM concentrations) rather than
      contributing to Pseudomonas aeruginosa-induced lung inflammation (as measured by
      leukocyte recruitment and cytokine concentration in the alveolar compartment).
      CONCLUSIONS: We show that pre-exposure to SiO2 nanoparticles increases mice
      susceptibility to lethal pneumonia but independently of macrophage phagocytic
      function. The deleterious effects of SiO2 nanoparticle exposure during
      Pseudomonas aeruginosa-induced pneumonia are related to alterations of the
      alveolar-capillary barrier rather than to modulation of the inflammatory
      responses.

PMID- 25605550
TI  - Bioanalytical evaluation of Cinnamomum zeylanicum essential oil.
AB  - This manuscript describes the antioxidant activity of essential oil of Cinnamon
      (Cinnamomum zeylanicum) bark extracted by supercritical fluid extraction (SCFE),
      hydro distillation and steam distillation. The cinnamon bark essential oil
      exhibited a wide range of total phenolic contents, total flavonoid contents,
      reducing power, inhibition of linoleic acid peroxidation and DPPH radical
      scavenging activity (IC50). Bioactivity of cinnamon essential oil was assayed
      against various bacterial strains including Bacillus subtilis, Escherichia coli,
      Pastrurella multocida and Straphylococcus aureus and fungal strains including
      Aspergillus niger and Aspergillus flavus. More essential oil yield was obtained
      using SCFE in comparison to other methods. The oil extracted by SCFE was
      dominated by cinnamaldehyde, limonene, copaene, naphthalene, heptane,
      bicyclo[4.2.0]octa-1,3,5-triene and 2-propenal. Due to the presence of
      cinnamaldehyde in the essential oil of cinnamon bark it acts as a good
      antioxidant and antimicrobial agent. 

PMID- 25605551
TI  - The distinctive nature of HER2-positive gastric cancers.

PMID- 25605552
TI  - Prospective pilot study of a single daily dosage of trientine for the treatment
      of Wilson disease.
AB  - BACKGROUND: Wilson disease requires lifelong therapy, currently given daily in
      multiple divided dosages. AIM: To prospectively evaluate once-daily trientine as
      therapy for Wilson disease. METHODS:  STUDY GROUP: eight patients (seven males)
      aged 22-71 years with stable Wilson disease treated from 4 to 50 years. Patients
      were monitored for 3 months then for 12 months on a single daily dose of
      trientine (15 mg/kg). RESULTS: All patients remained clinically well. ALT and AST
      fluctuated in some, but none required treatment stoppages or side effects. Liver
      synthetic function was unchanged. Mean 24-h urine copper and zinc excretions at
      end of treatment were 313.4 +/- 191.7 and 2,214 +/- 1,346 MUg, respectively.
      CONCLUSIONS: Once-daily trientine should be explored further for possible
      maintenance therapy for WD. Single daily dose may improve adherence to therapy.
      Larger trials and longer-term follow-up will establish the safety and treatment
      efficacy of this once-daily treatment regimen for WD (registration: NCT01472874).

PMID- 25605553
TI  - Oncogenic Role of BOLL in Colorectal Cancer.
AB  - BACKGROUND: Boule-like RNA-binding protein (BOLL protein) is the progenitor of
      the Deleted in Azoospermia (DAZ) gene family. To date, previous studies have
      focused on the reproductive function of BOLL. While we were identifying new DNA
      methylation biomarkers for colorectal cancer (CRC), we found that BOLL protein
      was overexpressed in CRC. AIM: The aim of this study was to determine the role of
      BOLL in CRC by epigenetic and functional studies in vivo and in vitro. METHODS:
      BOLL promoter methylation and expression were determined by MethyLight, RT-PCR,
      Western blot, and immunohistochemistry. The functional role of BOLL in CRC was
      evaluated by cell proliferation, colony formation, migration and invasion, cell
      cycle status, and tumor growth in a xenograft model. RESULTS: BOLL promoter
      methylation was enhanced in CRC tissues compared with normal colorectal tissues
      [97/124 (78 %) vs. 2/124 (2 %)]. However, the mean immunoreactivity score of CRC
      tissues and paired adjacent normal tissues was 8.15 +/- 0.18 (SD) and 3.35 +/-
      0.19 (SD), respectively (p < 0.01). No significant association was observed
      between immunoreactivity score and clinicopathological parameters, including age,
      gender, tumor size, tumor differentiation, and tumor node metastasis stage.
      Expression of BOLL in CRC cell lines significantly enhanced cell proliferation (p
      < 0.01), colony formation (p < 0.01), and migration (p < 0.01). In BOLL
      expressing cells, the percentage of cells in S-phase of the cell cycle was
      significantly increased. Tumor volume in BOLL xenografted mice was significantly
      enhanced after subcutaneous implantation (p < 0.01). CONCLUSIONS: Our study
      demonstrated an oncogenic role of BOLL in CRC despite tumor-specific promoter
      hypermethylation.

PMID- 25605554
TI  - Predictors of long-term renal outcome in lupus nephritis trials: lessons learned
      from the Euro-Lupus Nephritis cohort.
AB  - OBJECTIVE: There is a need to determine which response measures in lupus
      nephritis trials are most predictive of good long-term renal function. We used
      data from the Euro-Lupus Nephritis Trial to evaluate the performance of
      proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as
      predictors of good long-term renal outcome. METHODS: Patients from the Euro-Lupus
      Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6,
      or 12 months and with a minimum of 7 years of followup were included (n = 76). We
      assessed the ability of these clinical biomarkers at 3, 6, and 12 months after
      randomization to predict good long-term renal outcome (defined as a serum Cr
      value <=1.0 mg/dl) at 7 years. Receiver operating characteristic curves were
      generated to assess parameter performance at these time points and to select the
      best cutoff for individual parameters. Sensitivity and specificity were
      calculated for the parameters alone and in combination. RESULTS: A proteinuria
      value of <0.8 gm/day at 12 months after randomization was the single best
      predictor of good long-term renal function (sensitivity 81% and specificity 78%).
      The addition of serum Cr to proteinuria as a composite predictor did not improve
      the performance of the outcome measure; addition of urinary RBCs as a predictor
      significantly decreased the sensitivity to 47%. CONCLUSION: This study
      demonstrates that the level of proteinuria at 12 months is the individual best
      predictor of long-term renal outcome in patients with lupus nephritis. Inclusion
      of urinary RBCs as part of a composite outcome measure actually undermined the
      predictive value of the trial data. We therefore suggest that urinary RBCs should
      not be included as a component of clinical trial response criteria in lupus
      nephritis.

PMID- 25605555
TI  - Anticoagulation in patients with mechanical heart valves: follow the guidelines!

PMID- 25605556
TI  - Droplet generation via a single bubble transformation in a nanofluidic channel.
AB  - Here we report the first demonstration on droplet generation from the
      transformation of a single bubble in a nanofluidic channel by a laser-induced
      jet. A viscous two-dimensional Rayleigh-Plesset-type model is derived to describe
      the bubble dynamics in the nanofluidic channel, which accounts for the effect of
      shear stresses from the channel wall. The droplet generation (number and volume)
      is investigated experimentally by controlling the jet velocity via laser energy
      and distance. This study expands the understanding of jetting in the nanofluidic
      channel and demonstrates a novel method for femtoliter-volume single or multiple
      droplet formation. It is envisioned that this work will open new doors in on
      demand generation of nanodroplets. 

PMID- 25605558
TI  - Longitudinal perspective is needed to improve postpartum health.

PMID- 25605557
TI  - Modification of bafilomycin structure to efficiently synthesize solid-state NMR
      probes that selectively bind to vacuolar-type ATPase.
AB  - Bafilomycin (Baf) is one of the most potent inhibitors of vacuolar-type ATPase,
      which is strongly implicated in age-related diseases. However, the binding site
      of the antibiotic on the protein remains unclear because of the complexity of the
      structure of Baf bound to the target subunit in the transmembrane region. For
      conducting structural studies by applying solid-state NMR, which is one of the
      most promising methodologies available for structural analysis in membrane
      system, preparing bioactive fluorinated Baf analogues is essential. In this study
      two Baf analogues were carefully designed and efficiently synthesized through the
      convergent coupling of three segments. Biological evaluation revealed that the
      activity of 24-F-Baf was comparable to that of Baf, indicating its utility as a
      potential probe for solid-state NMR analysis. By contrast, desmethylated 24-F-Baf
      exhibited markedly diminished activity. The absence of two methyl groups caused a
      critical conformational change in the macrocyclic core structure necessary for
      binding to the target protein. 

PMID- 25605559
TI  - The effect of knee flexion and rotation on the tibial tuberosity-trochlear groove
      distance.
AB  - PURPOSE: The purpose was to measure the effect of flexion and additional rotation
      of the femur relative to the tibia on the tuberosity-trochlear groove distance
      (TT-TG) in the same subject in 20 cadaveric knees joint. METHODS: In 20 human
      adult cadavers, formal fixed knees (age: 81.9 years, SD 12.3; 10 female) CT scans
      were performed in extension and 30 degrees  of flexion as well as in neutral,
      maximal possible internal (IR), and external rotation (ER). On superimposed CT
      scan images, TT-TG was measured in each position. TT-TG measurements were
      correlated in all knee positions. RESULTS: TT-TG in full extension/neutral
      rotation was 7.8 mm (SD 3.4, range, 2.4-15.3). TT-TG in full extension and IR was
      significantly lower, and TT-TG in full extension and ER was significantly higher
      than in neutral rotation (5.4 +/- 2.3 vs. 10.9 +/- 4.8 mm; P < 0.001). IR and ER
      varied between 1.0 degrees -7.6 degrees  and 0.2 degrees -9.2 degrees ,
      respectively. TT-TG in 30 degrees  flexion/neutral rotation was 3.9 mm (SD 1.8,
      range, 1.3-7.8), which was significantly lower than in full extension and neutral
      rotation (P < 0.001). TT-TG in 30 degrees  flexion and IR was significantly
      lower, and TT-TG in 30 degrees  flexion and ER was significantly higher than
      values obtained in neutral rotation (2.7 +/- 1.2 vs. 6.5 +/- 3.4 mm; P < 0.001).
      IR and ER in 30 degrees  flexion varied between 0.6 degrees -10.7 degrees  and
      1.9 degrees -13.0 degrees , respectively. CONCLUSION: Flexion as well as rotation
      of the knee joint significantly alters the TT-TG. These results may have wider
      clinical relevance in assessing TT-TG and further decisions based on it.

PMID- 25605561
TI  - Aortic dissection in a young adolescent: never too late to solve a case.

PMID- 25605560
TI  - Oversizing the tibial component in TKAs: incidence, consequences and risk
      factors.
AB  - PURPOSE: The incidence of anteroposterior overhang of the tibial component after
      TKA and its effect on clinical outcome were investigated, and the morphometric
      characteristics of the knees in which tibial baseplates were oversized were
      identified. METHOD: One hundred and fourteen consecutive TKAs were
      retrospectively assessed. The dimensions of the tibia were measured on a pre
      operative CT scan and were compared with those of the implanted tibial component.
      We analysed the effect of anteroposterior and mediolateral size variations on
      clinical outcomes 1 year after surgery. RESULTS: An anteroposterior overhang was
      observed in 87 % of cases on the lateral plateau, in 88 % on the central plateau
      and in 25 % on the medial tibial plateau. The mean post-pre-operative size
      differences were 3.2 +/- 2.7, 2.8 +/- 2.7 and -1.6 +/- 2.3 mm, respectively.
      (Positive value means oversizing). A mediolateral overhang of the tibial
      component was found in 61 % of the patients. Oversizing was significantly greater
      and more frequent in females. Patients oversized in the anteroposterior dimension
      had lower post-operative pain scores. Patients with mediolateral oversizing had
      decreased flexion 1 year after surgery. Anteroposterior oversizing was observed
      more frequently in patients with asymmetric tibial plateaus, while mediolateral
      oversizing was observed more frequently in patients with small tibias.
      CONCLUSIONS: This study demonstrates that the incidence of oversized tibial
      plateau components is surprisingly high and that functional outcomes are lower in
      the case of mediolateral or anteroposterior oversizing. The risk of oversizing
      could be predicted as it occurs predominantly in patients with asymmetric
      proximal tibia and/or small tibia. LEVEL OF EVIDENCE: IV.

PMID- 25605562
TI  - Sudden death due to acute adrenal crisis.

PMID- 25605563
TI  - Subclass-specific labeling of protein-reactive natural products with customized
      nucleophilic probes.
AB  - Natural products represent a rich source of bioactive compounds that constitute a
      large fraction of approved drugs. Among those are molecules with electrophilic
      scaffolds, such as Michael acceptors, beta-lactams, and epoxides that
      irreversibly inhibit essential enzymes based on their catalytic mechanism. In the
      search for novel bioactive molecules, current methods are challenged by the
      frequent rediscovery of known chemical entities. Herein small nucleophilic probes
      that attack electrophilic natural products and enhance their detection by HPLC-UV
      and HPLC-MS are introduced. A screen of diverse probe designs revealed one
      compound with a desired selectivity for epoxide- and maleimide-based antibiotics.
      Correspondingly, the natural products showdomycin and phosphomycin could be
      selectively targeted in extracts of their natural producing organism, in which
      the probe-modified molecules exhibited superior retention and MS detection
      relative to their unmodified counterparts. This method may thus help to discover
      small, electrophilic molecules that might otherwise easily elude detection in
      complex samples. 

PMID- 25605564
TI  - Sleep-related road collisions.

PMID- 25605565
TI  - A three-dimensional self-opening intraneural peripheral interface (SELINE).
AB  - OBJECTIVE: In this study we present the development and testing in a rat model of
      the self-opening neural interface (SELINE), a novel flexible peripheral neural
      interface. APPROACH: This polyimide-based electrode has a three-dimensional
      structure that provides an anchorage system to the nerve and confers stability
      after implant. This geometry has been achieved by means of the plastic
      deformation of polyimide. Mechanical and electrochemical characterizations have
      been performed to prove the integrity of the electrode with very good results.
      Functionality of SELINEs for fascicular stimulation has been tested during in
      vivo acute experiments in the rat. Chronic implants were made to test the
      biocompatibility of the device. MAIN RESULTS: Results showed that SELINEs
      significantly improve mechanical anchorage to the nerve. Stimulation stability is
      considerably enhanced compared to common planar transversal electrodes and
      stimulation selectivity is increased for some motor fascicles. Chronic
      experimental results showed that SELINEs neither produce changes in the
      fascicular organization of sciatic nerves nor signs of nerve degeneration.
      SIGNIFICANCE: The presented three-dimensional electrode provides an effective
      anchorage system to the nervous tissue that can improve the stability of the
      implant for acute and chronic studies.

PMID- 25605566
TI  - Surgical complications after open and laparoscopic surgery for perforated peptic
      ulcer in a nationwide cohort.
AB  - BACKGROUND: Surgery for perforated peptic ulcer (PPU) is associated with a risk
      of complications. The frequency and severity of reoperative surgery is poorly
      described. The aims of the present study were to characterize the frequency,
      procedure-associated risk and mortality associated with reoperation after surgery
      for PPU. METHODS: All patients treated surgically for PPU in Denmark between 2011
      and 2013 were included. Baseline and clinical data, including 90-day mortality
      and detailed information on reoperative surgery, were collected from the Danish
      Clinical Register of Emergency Surgery. Distribution frequencies of reoperation
      stratified by type of surgical approach (laparoscopy or open) were reported. The
      crude and adjusted risk associations between surgical approach and reoperation
      were assessed by regression analysis and reported as odds ratio (OR) with 95 per
      cent c.i. Sensitivity analyses were carried out. RESULTS: A total of 726 patients
      were included, of whom 238 (32.8 per cent) were treated laparoscopically and 178
      (24.5 per cent) had a laparoscopic procedure converted to laparotomy. Overall,
      124 (17.1 per cent) of 726 patients underwent reoperation. A persistent leak was
      the most frequent cause (43 patients, 5.9 per cent), followed by wound dehiscence
      (34, 4.7 per cent). The crude risk of reoperative surgery was higher in patients
      who underwent laparotomy and those with procedures converted to open surgery than
      in patients who had laparoscopic repair: OR 1.98 (95 per cent c.i. 1.19 to 3.27)
      and 2.36 (1.37 to 4.08) respectively. The difference was confirmed when adjusted
      for age, surgical delay, co-morbidity and American Society of Anesthesiologists
      fitness grade. However, the intention-to-treat sensitivity analysis (laparoscopy
      including conversions) demonstrated no significant difference in risk. The risk
      of death within 90 days was greater in patients who had reoperation: crude and
      adjusted OR 1.53 (1.00 to 2.34) and 1.06 (0.65 to 1.72) respectively. CONCLUSION:
      Reoperation was necessary in almost one in every five patients operated on for
      PPU. Laparoscopy was associated with lower risk of reoperation than laparotomy or
      a converted procedure. However, there was a risk of bias, including confounding
      by indication.

PMID- 25605567
TI  - Phosphate addition enhanced soil inorganic nutrients to a large extent in three
      tropical forests.
AB  - Elevated nitrogen (N) deposition may constrain soil phosphorus (P) and base
      cation availability in tropical forests, for which limited evidence have yet been
      available. In this study, we reported responses of soil inorganic nutrients to
      full factorial N and P treatments in three tropical forests different in initial
      soil N status (N-saturated old-growth forest and two less-N-rich younger
      forests). Responses of microbial biomass, annual litterfall production and
      nutrient input were also monitored. Results showed that N treatments decreased
      soil inorganic nutrients (except N) in all three forests, but the underlying
      mechanisms varied depending on forests: through inhibition on litter
      decomposition in the old-growth forest and through Al(3+) replacement of Ca(2+)
      in the two younger forests. In contrast, besides great elevation in soil
      available P, P treatments induced 60%, 50%, 26% increases in sum of exchangeable
      (K(+)+Ca(2+)+Mg(2+)) in the old-growth and the two younger forests, respectively.
      These positive effects of P were closely related to P-stimulated microbial
      biomass and litter nutrient input, implying possible stimulation of nutrient
      return. Our results suggest that N deposition may result in decreases in soil
      inorganic nutrients (except N) and that P addition can enhance soil inorganic
      nutrients to support ecosystem processes in these tropical forests. 

PMID- 25605568
TI  - Breast cancer survivors' barriers and motives for participating in a group-based
      physical activity program offered in the community.
AB  - PURPOSE: The purpose of this qualitative study was to explore the barriers and
      motives experienced by women attending an 8-week group-based physical activity
      program offered in the community following treatment for breast cancer. METHODS:
      Seven women were interviewed during the first and last week of the program. Data
      were analyzed using thematic analysis. RESULTS: Factors that hindered women's
      continued participation could be subdivided into situational barriers, which
      encompassed community (i.e., distance of center and traffic) and institutional
      factors (i.e., competing roles and responsibilities), and internal barriers,
      which consisted of cancer-specific limitations. Motives for initial and continued
      participation were situational (i.e., gaining social support, networking, and
      being around similar others) and internal (i.e., feeling a sense of personal
      fulfillment, acquiring health benefits, and recovering from cancer). CONCLUSIONS:
      The findings contribute to a deeper understanding of women's motives to engage in
      a group-based physical activity program after treatment for breast cancer.
      Further, they underscore the necessity of considering situational and internal
      barriers when developing group-based physical activity programs to increase
      regular participation, optimize adherence, and reduce drop-out.

PMID- 25605569
TI  - Role of baseline echocardiography prior to initiation of anthracycline-based
      chemotherapy in breast cancer patients.
AB  - BACKGROUND: Anthracycline adjuvant therapy has taken a particular role in the
      treatment of early stage breast cancer with an associated decrease in rates of
      both relapse and death. Their success however has been limited by their
      myelosuppression and their well-established risk of cardiac dysfunction.
      Guidelines have emerged that would limit the maximum lifetime dose of
      anthracyclines and make a baseline assessment and periodic monitoring of cardiac
      function part of the routine practice, which could be cumbersome, and may condemn
      the patient to an unwarranted modification of his/her regimen. Our study aimed at
      assessing the incidence of abnormal baseline echocardiography in asymptomatic
      women with breast cancer prior to anthracycline therapy and establishing risk
      criteria associated with abnormal echocardiograms at baseline. METHODS: 220
      Patients seen at AUBMC (American University of Beirut Medical Center) who had non
      metastatic breast cancer, and had an echocardiography performed before starting
      anthracycline chemotherapy were chosen. Data about demographic characteristics,
      tumor characteristics, baseline echocardiography results, and change in clinical
      decision was collected. Patients with suboptimal (less than 50%) ejection
      fraction (EF) on baseline echocardiography were analyzed for the prevalence of
      cardiac risk factors. Results were compared to those among the overall study
      group using Fisher's Exact test. A p- value of = < 0.05 was used as reference for
      statistical significance. RESULTS: All 220 of our patients had received a
      baseline echo prior to initiation of anthracycline therapy. 6.7% of these
      patients had already some abnormality in wall motion but only 2.7% had a
      suboptimal ejection fraction. 1.3% had a change in chemotherapy regimen based on
      ejection fraction. The patients with depressed EF had higher rates of CAD
      (coronary artery disease), diabetes, hypertension and dyslipidemia than the
      overall study group but without statistical significance. CONCLUSIONS: Our study,
      as well as the previous contingent studies raise the question about routine
      echocardiography prior to anthracycline therapy and might eventually lead to a
      modification of current practice guidelines.

PMID- 25605570
TI  - Real-time symptomatic case of transfusion-transmitted dengue.
AB  - BACKGROUND: Dengue virus transmission by blood transfusion is a rarely reported
      event. CASE REPORT: During a dengue outbreak in Sao Paulo city, a regular
      plateletpheresis donor informed the blood bank of being diagnosed a few days
      after donation. The recipient was hospitalized and displayed symptoms and
      laboratory evidence of dengue after transfusion. RESULTS: The donor was
      immunoglobulin (Ig)G, IgM, and polymerase chain reaction nonreactive on the index
      sample, seroconverting 20 days later. The platelet units were transfused into two
      patients. One of them developed fever 3 days after transfusion, with high viral
      load. His pretransfusion sample was negative for IgG, IgM, and dengue RNA, while
      the second recipient did not show any symptoms nor laboratory evidence of dengue
      infection. CONCLUSIONS: This case brings additional evidence that dengue is
      indeed transmissible by blood transfusion and clinical manifestations, although
      rare, do occur.

PMID- 25605572
TI  - Teaching New Materials and Techniques for Fixed Dental Prostheses in Dental
      Schools in the United States and Canada: A Survey.
AB  - PURPOSE: Tooth-supported fixed dental prostheses (FDPs) remain an extensive
      therapeutic option, with new materials and a digital fabrication process
      gradually replacing traditional methods. The variety of advances calls for dental
      schools to expand the teaching of this field. Our aim was to examine the nature
      and the amount of theoretical and practical training in clinical FDP courses, and
      the extent to which new methods and innovations in the field are being
      integrated. MATERIALS AND METHODS: Data were collected using an online
      questionnaire including theoretical and practical teaching regarding clinical
      courses, restorative materials, and new fabrication methods, which was sent to 58
      dental schools in North America. RESULTS: A total of 36 schools responded to the
      survey for a response rate of 62.1%. All the schools teach theoretical and
      practical porcelain-fused-to-metal (PFM) restorations, and almost all the schools
      teach full-metal FDPs. In more than half (57.1%) of the schools, zirconia-based
      FDPs are placed by students. Students place partial veneer FDPs in less than one
      fifth (17.9%) of the schools. The average number of restorations required for
      completion of the clinical course is 7.3 FDP units. The respondents assessed that
      of the total FDPs placed by students in the clinical course, tooth-color coping
      (zirconia/alumina/porcelain) FDPs constituted 16.2%. None of the schools produce
      computer-assisted design/computer-assisted manufacturing copings or crowns within
      the school. CONCLUSIONS: All North American dental schools include teaching and
      placement of PFM restorations in their curriculum, but only one-third teach
      ceramic-based crowns. The low average number of required crowns may lead to
      graduates not being exposed to and trained in up-to-date dental restorative
      materials and techniques.

PMID- 25605571
TI  - Psychopathology among parents of children and adolescents with separation anxiety
      disorder.
AB  - OBJECTIVE: To examine psychopathology among parents of children and adolescents
      with separation anxiety disorder (SAD). METHOD: A case-control design was
      applied: parents of children and adolescents suffering from SAD (n = 30; age:
      10.7 +/- 1.8 a) were compared with parents of youth without any psychiatric
      disease (n = 30; age: 11.2 +/- 1.8 a). The SCID-I, a structured clinical
      interview to assess psychopathology, was applied among the parents group.
      RESULTS: Parents of children and adolescents suffering from SAD exhibited a
      significantly higher prevalence of psychopathology, mainly anxiety disorders and
      mood disorders, in comparison with the control group. Within anxiety disorders,
      mothers predominantly suffered from social phobia and specific phobia. Fathers
      most frequently suffered from obsessive-compulsive disorder and social phobia.
      Maternal anxiety disorder (current and lifetime) and maternal affective disorder
      (lifetime) proved to be significant predictors of SAD in youth. CONCLUSIONS: The
      associations between parents' psychopathology and the development of SAD in their
      children are discussed in the light of clinical implications, both in terms of
      psychotherapeutic care as well as treatment outcome.

PMID- 25605573
TI  - Zinc(II)-catalyzed intermolecular hydrative aldol reactions of 2-en-1-ynamides
      with aldehydes and water to form branched aldol products regio- and
      stereoselectively.
AB  - This work describes zinc(II)-catalyzed hydrative aldol reactions of 2-en-1
      ynamides with aldehydes and water to afford branched aldol products regio- and
      stereoselectively. The anti and syn selectivity can be modulated by the sizes of
      sulfonamides to yield E- and Z-configured zinc(II) dienolates selectively. This
      new reaction leads to enantiopure aldol products by using a cheap chiral
      sulfonamide. The mechanistic analysis reveals that the sulfonamide amides of the
      substrates can trap a released proton to generate dual acidic sites to activate a
      carbonyl allylation reaction. 

PMID- 25605575
TI  - Finding flavor in food.
AB  - As researchers use metabolomics to understand how chemicals influence flavor,
      Jeffrey Perkel takes a closer look at how science is changing the way we look at
      food. 

PMID- 25605576
TI  - Micropatterning strategies to engineer controlled cell and tissue architecture in
      vitro.
AB  - Micropatterning strategies, which enable control over cell and tissue
      architecture in vitro, have emerged as powerful platforms for modelling tissue
      microenvironments at different scales and complexities. Here, we provide an
      overview of popular micropatterning techniques, along with detailed descriptions,
      to guide new users through the decision making process of which micropatterning
      procedure to use, and how to best obtain desired tissue patterns. Example
      techniques and the types of biological observations that can be made are provided
      from the literature. A focus is placed on microcontact printing to obtain co
      cultures of patterned, confluent sheets, and the challenges associated with
      optimizing this protocol. Many issues associated with microcontact printing,
      however, are relevant to all micropatterning methodologies. Finally, we briefly
      discuss challenges in addressing key limitations associated with current
      micropatterning technologies. 

PMID- 25605577
TI  - Simultaneous isolation of enriched myoblasts and fibroblasts for migration
      analysis within a novel co-culture assay.
AB  - Skeletal muscle injury elicits the activation of satellite cells and their
      migration to the wound area for subsequent terminal differentiation and tissue
      integration. However, interstitial fibroblasts recruited to the site of injury
      promote deposition of fibrotic tissue, which hampers myoblast-mediated muscle
      regeneration. Currently, analysis of myoblast migration in vitro can be
      accomplished using chemotactic, cell-exclusion, or wound healing assays. Yet, to
      investigate cell motility following skeletal muscle damage more accurately,
      migration assays need to better simulate the repair process. Here we present a
      protocol for the simultaneous isolation of myoblasts and fibroblasts from the
      same muscle tissue, ensuring the consistent generation of enriched, purified, and
      matched cell populations at a low passage number. We then describe a wound assay
      that uses a novel approach to the co-culture of myoblasts and fibroblasts to
      mimic the injured environment more closely than other established methods. Using
      this assay, we demonstrate that fibroblasts are able to increase myoblast
      migration significantly, validating our new in vitro method. As the observed
      effect on migration is most likely mediated by secreted factors, our assay could
      easily be extended to include antibody-based protein analysis of secreted factors
      in animal or human systems. 

PMID- 25605578
TI  - Abridged adapter primers increase the target scope of Hi-Plex.
AB  - Previously, we reported Hi-Plex, an amplicon-based method for targeted massively
      parallel sequencing capable of generating 60 amplicons simultaneously. In further
      experiments, however, we found our approach did not scale to higher amplicon
      numbers. Here, we report a modification to the original Hi-Plex protocol that
      includes the use of abridged adapter oligonucleotides as universal primers
      (bridge primers) in the initial PCR mixture. Full-length adapter primers
      (indexing primers) are included only during latter stages of thermal cycling with
      concomitant application of elevated annealing temperatures. Using this approach,
      we demonstrate the application of Hi-Plex across a broad range of amplicon
      numbers (16-plex, 62-plex, 250-plex, and 1003-plex) while preserving the low
      amount (25 ng) of input DNA required. 

PMID- 25605579
TI  - High-throughput detection of DNA double-strand breaks using image cytometry.
AB  - Assessment of gammaH2AX expression for studying DNA double-strand break formation
      is often performed by manual counting of foci using immunofluorescence
      microscopy, an approach that is laborious and subject to significant foci
      selection bias. Here we present a novel high-throughput method for detecting DNA
      double-strand breaks using automated image cytometry assessment of cell average
      gammaH2AX immunofluorescence. Our technique provides an expedient, high
      throughput, objective, and cost-effective method for gammaH2AX analysis. 

PMID- 25605580
TI  - Preparation of amino acid mixtures for cell-free expression systems.
AB  - Here we present a procedure for preparing amino acid mixtures--having both the
      desired composition and a physiological pH--at high concentrations for cell-free
      expression systems. Up to 2.1 mg/mL of active protein was synthesized in batch
      mode reactions with an all Escherichia coli cell-free expression system. Our
      method is fast, easy to execute, and economically advantageous compared to
      expensive commercial kits, making it useful for high-throughput experiments,
      incorporation of nonstandard amino acids, and cell-free metabolic engineering.

PMID- 25605581
TI  - Variation in the place of death among nursing home residents in France.
AB  - OBJECTIVES: recent studies have reported that hospitals have become a common
      place of death for nursing home residents. This study aimed to (i) measure
      variations in the proportion of in-hospital deaths across regions after
      adjustment for facility-level characteristics and (ii) identify environmental
      risk factors that might explain these variations in France. DESIGN: a cross
      sectional retrospective survey was conducted in 2013. SETTING AND PARTICIPANTS:
      coordinating physicians in 3,705 nursing homes in France. MEASUREMENTS: a
      regression model was used to construct risk-adjusted rates of in-hospital deaths
      considering the facilities' characteristics. At the regional level, the outcome
      was defined as the difference between the observed rate of in-hospital deaths and
      the expected risk-adjusted rate. Values exceeding zero indicated rates that
      exceeded the national predicted rate of in-hospital deaths and thus highlighted
      regions in which the risk-adjusted probability for nursing home residents to die
      in a hospital was greater than average. RESULTS: among 70,119 nursing home
      decedents, 25.4% (n = 17,789) died in hospitals. The characteristics of the
      facilities had a significant influence on the proportion of in-hospital deaths
      among the nursing home decedents. However, after adjustment for these facility
      level risk factors, the proportion of nursing homes that reported worse-than
      average outcomes showed significant variation (range 26.0-79.6%). At the regional
      level, both the rate of acute hospital beds and the rate of general practitioners
      were found to be strongly correlated with the probability of reporting worse-than
      average outcomes (P < 0.001). CONCLUSION: our study demonstrates the existence of
      major differences across regions in France and highlights the need for targeted
      interventions regarding end-of-life care in nursing home facilities.

PMID- 25605582
TI  - Accelerated partial breast irradiation using intensity-modulated radiotherapy
      versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised
      controlled trial.
AB  - BACKGROUND: Accelerated partial breast irradiation (APBI) has been introduced as
      an alternative treatment method for selected patients with early stage breast
      cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical
      advantage of a further increase in dose conformity compared with three
      dimensional techniques, with more normal tissue sparing. The aim of this
      randomised trial is to compare the local recurrence and survival of APBI using
      the IMRT technique after breast-conserving surgery to conventional whole-breast
      irradiation (WBI) in early stage BC. METHODS: This study was performed at the
      University of Florence (Florence, Italy). Women aged more than 40years affected
      by early BC, with a maximum pathological tumour size of 25mm, were randomly
      assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the
      APBI arm received a total dose of 30 Gy to the tumour bed in five daily
      fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the
      tumour bed of 10Gy in five fractions. The primary end-point was occurrence of
      ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention
      to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895.
      FINDINGS: A total of 520 patients were randomised (260 to external WBI and 260 to
      APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0
      years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases)
      in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group
      (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two
      groups (log rank test p=0.86). We identified seven deaths in the WBI group and
      only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for
      the WBI group and 99.4% for the APBI group. The APBI group presented
      significantly better results considering acute (p=0.0001), late (p=0.004), and
      cosmetic outcome (p=0.045). INTERPRETATION: To our knowledge, this is the first
      randomised study using the IMRT technique for APBI delivery. No significant
      difference in terms of IBTR and overall survival was observed between the two
      arms. APBI displayed a significantly better toxicity profile.

PMID- 25605583
TI  - Not addressing the root cause: An analysis of submissions made to the South
      Australian Government on a Proposal to Protect Midwifery Practice.
AB  - BACKGROUND: Reports of unregulated birth workers attending birth at home, with no
      registered midwife in attendance (freebirth), have become more frequent in
      Australia in recent years. A Coronial Inquiry (2012) into the deaths of three
      babies born at home in South Australia resulted in a call for legislation to
      restrict the practice of midwifery to registered midwives. A Proposal to Protect
      Midwifery Practice in South Australia was issued as a consultation paper in
      January 2013. AIM: To report the views of those making a submission to the
      Proposal to Protect Midwifery Practice in South Australia. METHODS: Thirty
      submissions to the South Australian Government were downloaded, read and
      thematically analysed. FINDINGS: Twenty-five (81%) submissions supported the
      legislation, 5 (16%) opposed it and 2 (6%) were neither for nor against. Support
      for the proposed legislation was strong, however the underlying root causes that
      have led to the rise of UBWs attending homebirth in Australia were not addressed.
      Recommendations called for all stakeholders to work with women to develop a
      better framework of care that respected and met their needs and choices whilst
      safeguarding maternal and neonatal health. CONCLUSIONS: The Proposal to Protect
      Midwifery Practice may promote greater protection of midwifery practice however,
      Private Indemnity Insurance (PII), collaborative agreements and power struggles
      associated with the medical domination of childbirth continue to marginalise
      homebirth and prevent women from accessing the care they want and need. These
      unresolved issues represent the root causes for UBWs attending homebirth; hence
      the proposal is only a partial solution.

PMID- 25605585
TI  - Lactic acid as an invaluable green solvent for ultrasound-assisted scalable
      synthesis of pyrrole derivatives.
AB  - Lactic acid has been used as a bio-based green solvent to study the ultrasound
      assisted scale-up synthesis. We report here, for the first time, on the novel and
      scalable process for synthesis of pyrrole derivatives in lactic acid solvent
      under ultrasonic radiation. Eighteen pyrrole derivatives have been synthesized in
      lactic acid solvent under ultrasonic radiation and characterized by (1)H NMR, IR,
      ESI MS. The results show, under ultrasonic radiation, lactic acid solvent can
      overcome the scale-up challenges and exhibited many advantages, such as bio-based
      origin, shorter reaction time, lower volatility, higher yields, and ease of
      isolating the products. 

PMID- 25605586
TI  - MouthLab: A Tricorder Concept Optimized for Rapid Medical Assessment.
AB  - The goal of rapid medical assessment (RMA) is to estimate the general health of a
      patient during an emergency room or a doctor's office visit, or even while the
      patient is at home. Currently the devices used during RMA are typically "all-in
      one" vital signs monitors. They require time, effort and expertise to attach
      various sensors to the body. A device optimized for RMA should instead require
      little effort or expertise to operate and be able to rapidly obtain and
      consolidate as much information as possible. MouthLab is a battery powered hand
      held device intended to acquire and evaluate many measurements such as non
      invasive blood sugar, saliva and respiratory biochemistry. Our initial prototype
      acquires standard vital signs: pulse rate (PR), breathing rate (BR), temperature
      (T), blood oxygen saturation (SpO2), blood pressure (BP), and a three-lead
      electrocardiogram. In our clinical study we tested the device performance against
      the measurements obtained with a standard patient monitor. 52 people participated
      in the study. The measurement errors were as follows: PR: -1.7 +/- 3.5 BPM, BR:
      0.4 +/- 2.4 BPM, T: -0.4 +/- 1.24  degrees F, SpO2: -0.6 +/- 1.7%. BP systolic: 
      1.8 +/- 12 mmHg, BP diastolic: 0.6 +/- 8 mmHg. We have shown that RMA can be
      easily performed non-invasively by patients with no prior training. 

PMID- 25605584
TI  - Quality of life (QoL) impairments in patients with a pituitary adenoma: a
      systematic review of QoL studies.
AB  - PURPOSE: Pituitary adenomas give rise to physical and psychological symptoms,
      which may persist after biochemical cure. Growing attention has been paid to
      quality of life (QoL) in these patients. We aimed to systematically analyze QoL
      assessment methods and QoL outcome in these patients. METHODS: We conducted a
      systematic literature search up to January 2014 in PubMed, Web of Knowledge,
      PsycInfo and EMBASE. RESULTS: 102 papers assessing QoL in patients with a
      pituitary adenoma were included. In clinical (original) studies in which QoL was
      the primary outcome parameter (n = 54), 19 studies combined a generic
      questionnaire with a disease-specific questionnaire. QoL was found to be impaired
      in patients with active disease relative to controls, and generally improved
      during biochemical cure. However, no normalization occurred, with patients with
      remitted Cushing's disease demonstrating the smallest improvement. Somatic
      factors (e.g., hypopituitarism, sleep characteristics), psychological factors
      (illness perceptions) and health care environment (rural vs. urban) were
      identified as influencing factors. Intervention studies (predominantly evaluating
      medical interventions) have been found to improve QoL. CONCLUSIONS: The growing
      number of studies assessing QoL generally described the negative impact of
      pituitary adenomas. QoL research in this patient group could be further
      elaborated by the development of disease-specific questionnaires for prolactinoma
      and non-functioning adenoma, consequent use of generic and disease-specific
      questionnaires and using a long-term (longitudinal) follow-up. Surgical and
      pharmacological interventions improve but not normalize QoL. We postulate that
      there might be margin for further improvement of QoL, for instance by using
      psychosocial interventions, in addition to optimal medical treatment.

PMID- 25605588
TI  - A naphthalimide-based fluorescent probe for highly selective detection of
      histidine in aqueous solution and its application in in vivo imaging.
AB  - A naphthalimide-based fluorescent ensemble probe NPC for selectively detecting
      His in aqueous solution (10 mM HEPES, pH 7.4) has been reported. Moreover, the
      application of NPC in in vivo (both in Hela cells and in C. elegans) fluorescence
      imaging was carried out as well. 

PMID- 25605587
TI  - Indolamine 2,3-dioxygenase expression by monocytes and dendritic cell populations
      in hepatitis C patients.
AB  - Dendritic cells (DCs) play an important role in the induction of the primary
      immune response to infection. DCs may express the tryptophan-catabolizing enzyme
      indolamine2,3-dioxygenase (IDO), which is an inducer of immune tolerance. Because
      there is evidence that chronic hepatitis C virus (HCV) infection leads to
      functional impairment of certain DC populations, we analysed IDO expression in
      DCs and monocytes from chronically infected and recovered HCV patients. The IDO1
      and -2 expression was increased significantly in the monocytes of chronic HCV
      patients but, interestingly, not in those from recovered patients. The myeloid
      DCs from chronically infected HCV patients also showed enhanced IDO1 expression,
      while no change in either IDO1 or -2 was found for plasmacytoid DCs. Up
      regulation of IDO1 gene expression was confirmed by the presence of enhanced
      kynurenine/tryptophan ratios in the plasma from chronic HCV patients. Increased
      IDO1 and -2 expression was also observed in monocytes from healthy donors
      infected with an adapted mutant of the HCV JFH-1 strain ex vivo, confirming a
      direct effect of HCV infection. These changes in IDO expression could be
      prevented by treatment with the IDO inhibitor 1-methyl tryptophan (1-mT).
      Furthermore, maturation of monocyte-derived DCs from chronically infected HCV
      patients, as well as well as monocyte-derived DCs infected ex vivo with HCV, was
      impaired, but this was reversed by 1-mT treatment. This suggests that IDO
      inhibitors may be used to treat chronic HCV patients in vivo, in conjunction with
      current therapies, or to activate DCs from patients ex vivo, such that they can
      be administered back as a DC-based therapeutic vaccine. 

PMID- 25605590
TI  - Web-based child pornography: The global impact of deterrence efforts and its
      consumption on mobile platforms.
AB  - Our study is the first to look at mobile device use for child sexual exploitation
      material (CSEM) consumption, and at the global impact of deterrence efforts by
      search providers. We used data from Google, Bing, and Yandex to assess how web
      searches for CSEM are being conducted, both at present and historically. Our
      findings show that the blocking efforts by Google and Microsoft have resulted in
      a 67% drop in the past year in web-based searches for CSEM. Additionally, our
      findings show that mobile devices are a substantial platform for web-based
      consumption of CSEM, with tablets and smartphones representing 32% of all queries
      associated with CSEM conducted on Bing. Further, our findings show that a major
      search engine not located in the United States, Yandex, did not undertake
      blocking efforts similar to those implemented by Google and Microsoft and has
      seen no commensurate drop in CSEM searches and continues to profit from ad
      revenue on these queries. While the efforts by Google and Microsoft have had a
      deterrence effect in the United States, searchers from Russia and other locations
      where child pornography possession is not criminalized have continued to use
      these services. Additionally, the same lax enforcement environment has allowed
      searchers from the United States to utilize Yandex with little fear of detection
      or referral to United States law enforcement from the Russian authorities. 

PMID- 25605589
TI  - Direct and indirect antioxidant activity of polyphenol- and isothiocyanate
      enriched fractions from Moringa oleifera.
AB  - Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts
      used as nutritious food and traditional medicine. This study describes an
      efficient preparatory strategy to extract and fractionate moringa leaves by fast
      centrifugal partition chromatography (FCPC) to produce polyphenol and
      isothiocyanate (ITC) rich fractions. Characterization and further purification of
      these fractions showed that moringa polyphenols were potent direct antioxidants
      assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were
      effective indirect antioxidants assayed by induction of NAD(P)H quinone
      oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4
      [(alpha-l-rhamnosyloxy)benzyl]isothiocyanate and 4-[(4'-O-acetyl-alpha-l
      rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1
      inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as
      SF in inducing NQO1 activity. These findings suggest that moringa leaves contain
      a potent mixture of direct and indirect antioxidants that can explain its various
      health-promoting effects.

PMID- 25605591
TI  - Cytopathology: why did it take so long to thrive?
AB  - Lionel S. Beale of London made some of the earliest contributions to
      Cytopathology in the 1850-1860s. Cytopathology then experienced a 60+ year hiatus
      during which few advances were made. In 1927, Londoner Leonard S. Dudgeon
      published his wet film method for rapid intraoperative diagnosis and in 1928
      Greek-American George Papanicolaou and Romanian Aurel A. Babes independently
      discovered that cervical cancer can be diagnosed using vaginal smears; these were
      huge advancements. Yet, there was another hiatus where little progress was made
      which lasted until the publications of Papanicolaou and Trout in the early 1940s.
      After that, the field of exfoliative Cytopathology immediately flourished. None
      of the standard histories of Cytopathology explain these two gaps. Primary and
      secondary historical sources were examined to explain this pattern. The author
      concludes that the first hiatus is explained by the 19th Century pathology
      establishment's strong opposition to the doctrine of the uniqueness of cancer
      cells that was being pushed by only a few maverick pathologists; in fact, for
      many mainstream pathologists, cancer was rigidly defined by cell behavior
      (metastases and invasion) and not cell morphology well into the 20th Century.
      Biopsy-based diagnosis faced similar opposition but advanced more rapidly as it
      was possible to examine increased numbers of cells in a pattern that partially
      maintained their normal adjacencies and architecture. The second hiatus is
      explained by economic pressures supporting intraoperative frozen section
      diagnoses and, in the instance of vaginal smears, the embryonic state of the
      public campaign supporting the importance of early cancer diagnosis.

PMID- 25605592
TI  - Erratum to: Splice variants DNMT3B4 and DNMT3B7 overexpression inhibit cell
      proliferation in 293A cell line.

PMID- 25605593
TI  - Effects of copper on the preparation and characterization of Na-Ca-P borate
      glasses.
AB  - Glasses in the system Na2O-CaO-B2O3-P2O5: CuO have been prepared by melt
      quenching at 1200 degrees C and rapidly cooling at room temperature. The
      structural, optical and thermal properties have been investigated using X-ray
      diffraction (XRD), ultraviolet-visible (UV-VIS) spectroscopy, thermogravimetric
      differential thermal analysis (TG-DTA), Fourier transform infrared (FTIR)
      spectroscopy, high resolution scanning electron microscopy (HRSEM) with energy
      dispersive X-ray (EDX) spectroscopy and high resolution transmission electron
      microscope (HRTEM) with energy dispersive X-ray (EDAX). The amorphous and
      crystalline nature of these samples was verified by XRD. Glass transition,
      crystallization and thermal stability were determined by TG-DTA investigations.
      Direct optical energy band gaps before and after doping with different percents
      of copper oxide were evaluated from 4.81eV to 2.99eV indicated the role of copper
      in the glassy matrix by UV spectra. FTIR spectrum reveals characteristic
      absorption bands due to various groups of triangular and tetrahedral borate
      network. Due to the amorphous nature, the particles like agglomerates on the
      glass surface were investigated by the HRSEM analysis. The crystalline nature of
      the samples in XRD is confirmed by SAED pattern using HRTEM. 

PMID- 25605594
TI  - Mapping conformational heterogeneity of mitochondrial nucleotide transporter in
      uninhibited states.
AB  - One of the less well understood aspects of membrane transporters is the dynamic
      coupling between conformational change and substrate transport. NMR approaches
      are used herein to investigate conformational heterogeneity of the GTP/GDP
      carrier (GGC) from yeast mitochondria. NMR residual dipolar coupling (RDC)
      analysis of GGC in a DNA-origami nanotube liquid crystal shows that several
      structured segments have different generalized degrees of order (GDO), thus
      indicating the presence of conformational heterogeneity. Complete GDO mapping
      reveals asymmetry between domains of the transporter and even within certain
      transmembrane helices. Nucleotide binding partially reduces local structural
      heterogeneity, and the substrate binds to multiple sites along the transport
      cavity. These observations suggest that mitochondrial carriers in the uninhibited
      states are intrinsically plastic and structural plasticity is asymmetrically
      distributed among the three homologous domains. 

PMID- 25605595
TI  - An approach to creating a more realistic working model from a protein data bank
      entry.
AB  - An accurate model of three-dimensional protein structure is important in a
      variety of fields such as structure-based drug design and mechanistic studies of
      enzymatic reactions. While the entries in the Protein Data Bank (
      http://www.pdb.org ) provide valuable information about protein structures, a
      small fraction of the PDB structures were found to contain anomalies not reported
      in the PDB file. The semiempirical PM7 method in MOPAC2012 was used for
      identifying anomalously short hydrogen bonds, C-H?O/C-H?N interactions, non
      bonding close contacts, and unrealistic covalent bond lengths in recently
      published Protein Data Bank files. It was also used to generate new structures
      with these faults removed. When the semiempirical models were compared to those
      of PDB_REDO (http://www.cmbi.ru.nl/pdb_redo/), the clashscores, as defined by
      MolProbity ( http://molprobity.biochem.duke.edu/), were better in about 50% of
      the structures. The semiempirical models also had a lower root-mean-square
      deviation value in nearly all cases than those from PDB_REDO, indicative of a
      better conservation of the tertiary structure. Finally, the semiempirical models
      were found to have lower clashscores than the initial PDB file in all but one
      case. Because this approach maintains as much of the original tertiary structure
      as possible while improving anomalous interactions, it should be useful to
      theoreticians, experimentalists, and crystallographers investigating the
      structure and function of proteins.

PMID- 25605597
TI  - Binuclear cyclopentadienylrhenium hydride chemistry: terminal versus bridging
      hydride and cyclopentadienyl ligands.
AB  - Theoretical studies predict the lowest energy structures of the binuclear
      cyclopentadienylrhenium hydrides Cp2Re2H n (Cp = eta(5)-C5H5; n = 4, 6, 8) to
      have a central doubly bridged Re2(MU-H)2 unit with terminal eta(5)-Cp rings and
      the remaining hydrides as terminal ligands. However, the lowest energy Cp2Re2H2
      structure by more than 12 kcal mol(-1) has one terminal eta(5)-Cp ring, a
      bridging eta(3),eta(2)-Cp ring, and two terminal hydride ligands bonded to the
      same Re atom. The lowest energy hydride-free Cp2Re2 structure is a perpendicular
      structure with two bridging eta(3),eta(2)-Cp rings. The previously predicted bent
      singlet Cp2Re2 structure with terminal eta(5)-Cp rings and a formal Re-Re
      sextuple bond lies ~37 kcal mol(-1) above this lowest energy (eta(3),eta(2)
      Cp)2Re2 structure. The thermochemistry of the CpReH n and Cp2Re2H n systems is
      consistent with the reported synthesis of the permethylated derivatives Cp*ReH6
      and Cp*2Re2H6 (Cp* = eta(5)-Me5C5) as very stable compounds. Additionally,
      natural bond orbital analysis, atoms-in-molecules and overlap population density
      of-state in AOMIX were applied to present the existence of rhenium-rhenium
      multiple bonds.

PMID- 25605596
TI  - Targeting a cluster of arginine residues of neuraminidase to avoid oseltamivir
      resistance in influenza A (H1N1): a theoretical study.
AB  - Following the influenza A (H1N1) pandemic in Mexico and around the world in 2009,
      the numbers of oseltamivir-resistant clinical cases have increased through a
      mechanism that remains unclear. In this work, we focus on studying the mutated NA
      structures ADA71175 (GenBank) and 3CKZ (PDB ID). Recently crystallized NA (PDB
      ID: 3NSS) was used as a wild-type structure and template to construct the three
      dimensional (3D) structure of ADA71175. Then, the NA mutants and 3NSS natives as
      well as their refined monomer structures as determined through MD simulations
      (snapshots at 50 ns) were used as models to perform a docking study using a set
      of aryl-oseltamivir derivatives. These aryl-oseltamivir derivatives have better
      recognition properties than oseltamivir because of cation-pi interactions with a
      cluster of Arg residues (118, 292, and 371) at the binding site. This cluster of
      Arg residues represents a potential binding site for aryl-oseltamivir derivatives
      that are potentially new NA inhibitors.

PMID- 25605598
TI  - Theoretical study of the dimerization of aqueous beryllium cations.
AB  - The dimerization of monomeric beryllium species was studied via density
      functional theory (DFT) calculations, and the influences of deprotonation and
      substitution with various halide anions on the polymerization were explored. The
      results indicate that the dimerization was accomplished by aggregation followed
      by a nucleophilic attack reaction, and the hydrolysis that provides the
      nucleophilic hydroxyl group is a prerequisite for polymerization. An activation
      energy of 49.7 kJ mol(-1) and an aggregation energy of -52.2 kJ mol(-1) were
      found for the formation of Be2(OH)(H2O)6 (3+), indicating a exothermic reaction.
      Deprotonation promotes aggregation and increases the energy barrier to
      activation. Replacing a bound water with an F(-) anion makes aggregation more
      thermodynamically favorable, but it does not significantly change the energy
      barrier. It was concluded that the charge and electronegativity of the anion are
      crucial influences on the energy of the activation barrier, whereas the
      aggregation energy is influenced not only by the charge but also by the symmetry
      of the bridging structure in the aggregate.

PMID- 25605599
TI  - Effect of water in amorphous polyvinyl formal: insights from molecular dynamics
      simulation.
AB  - In this study, molecular dynamics simulations were performed to study the
      influence of water on polyvinyl formal. The effects of adding different
      concentrations of water (0, 0.23, 0.47, 0.94, 1.40, 1.86, 2.76, 3.65 and 4.52
      wt%) to a copolymer of polyvinyl acetal, polyvinyl alcohol, and polyvinyl acetate
      were investigated. Simulated results clearly indicated that the radius of
      gyration of the polymer chain decreased whereas the cohesive energy density
      increased with the addition of water molecules. The diffusion coefficient
      initially decreased and then monotonically increased with increasing water
      concentration, and the same trend was observed for the fractional free volume.
      The results provide insights into the molecular structural and physical
      properties of polyvinyl formal with different water contents.

PMID- 25605600
TI  - A mixed basis with off-center Gaussian functions for the calculation of the
      potential energy surfaces for pi-stacking interactions: dimers of benzene and
      planar C6.
AB  - A practical mixed basis set was developed to facilitate accurate calculations of
      potential energy surfaces for pi-stacking interactions. Correlation consistent
      basis sets (cc-PVXZ) were augmented by p-type Gaussian functions placed above and
      below the planes of C6 moieties. Moller-Plesset (MP2, SCS-MP2) and coupled
      cluster [CCSD(T)] calculations show that such generated basis sets provide an
      accurate description of pi-stacking systems with favorable computation times
      compared to the standard augmented basis sets. The addition of these off-center
      functions eliminates the linear dependence of the augmented basis sets, which is
      one of the most encountered numerical problems during calculation of the
      oligomers of polyaromatic hydrocarbons (PAH). In this work, we present a
      comparative study of the general characteristics of the potential energy surfaces
      for the parallel stacked and T-shape conformations of benzene and planar C6
      clusters, using a combination of cc-PVXZ and our optimized functions. We discuss
      properties, such as the depth and curvature of the potential functions, short and
      long distance behavior, and the frictional forces between two model monomers. 

PMID- 25605601
TI  - Theoretical studies of the nitrogen containing compounds adsorption behavior on
      Na(I)Y and rare earth exchanged RE(III)Y zeolites.
AB  - In this work, the adsorption behavior of nitrogen containing compounds including
      NH3, pyridine, quinoline, and carbazole on Na(I)Y and rare earth exchanged
      La(III)Y, Pr(III)Y, Nd(III)Y zeolites was investigated by density functional
      theory (DFT) calculations. The calculation results demonstrate that rare earth
      exchanged zeolites have stronger adsorption ability for nitrogen containing
      compounds than Na(I)Y. Rare earth exchanged zeolites exhibit strongest
      interaction with quinoline while weakest with carbazole. Nd(III)Y zeolites are
      found to have strongest adsorption to all the studied nitrogen containing
      compounds. The analysis of the electronic total charge density and electron
      orbital overlaps show that nitrogen containing compounds interact with zeolites
      by pi-electrons of the compounds and the exchanged metal atom. Mulliken charge
      population analysis also proves that adsorption energies are strongly dependent
      on the charge transfer between the nitrogen containing molecules and exchanged
      metal atom in the zeolites. 

PMID- 25605602
TI  - Quantum chemical studies on nanostructures of the hydrated methylimidazolium
      based ionic liquids.
AB  - The B3LYP and M06-2X suits of density functional theory in conjunction with the 6
      311++G(2d,2p) basis set were employed to investigate the nanostructures formed
      from the interaction between water molecules and ionic liquids based on
      methylimidazolium cation (MIM(+)) with the anions (X1-5 = CH3COO(-), CF3COO(-),
      NO3(-), BF4(-), and N(CN)2(-)) on a molecular level. Based on the calculated
      Gibbs free binding energies, the predicted stability order of nanostructures in
      the gas phase is [MIM]X1 > [MIM]X2 > [MIM]X3 > [MIM]X4 > [MIM]X5. The estimated
      solvation enthalpy of ions implied that the stability of anions NO3 (-) and
      CH3COO(-) in water is greater than those of MIM(+) and other anions. Tendency of
      hydrated anions to react with hydrated cations to form the solvated ion pairs is
      slightly smaller than the tendency of hydrated anions (cations) to react with
      unsolvated cations (anions). The strengths of the interactions in studied
      categories follow the trend X-W > MIM-W > [MIM]X -W.

PMID- 25605603
TI  - Molecular dynamics simulation of melting and crystallization processes of
      polyethylene clusters confined in armchair single-walled carbon nanotubes.
AB  - The confined interaction is important to understand the melting and
      crystallization of polymers within single-wall carbon tube (SWNT). However, it is
      difficult for us to observe this interaction. In the current work, the structures
      and behaviors of melting and crystallization for polyethylene (PE) clusters
      confined in armchair single-walled carbon nanotubes ((n,n)-SWNTs) are
      investigated and examined based on molecular dynamics (MD) simulations. The
      nonbonded energies, structures, Lindemman indices, radial density distributions,
      and diffusion coefficients are used to demonstrate the features of melting phase
      transition for PE clusters confined in (n,n)-SWNTs. The chain end-to-end distance
      (R(n)) and chain end-to-end distribution are used to examine the flexibility of
      the PE chain confined in SWNT. The global orientational order parameter (P2) is
      employed to reveal the order degree of whole PE polymer. The effect of
      polymerization degree on melting temperature and the influence of SWNT chirality
      on structure of PE cluster are examined and discussed. Results demonstrate that
      within the confined environment of SWNT, PE clusters adopt novel co-axial
      crystalline layer structure, in which parallel chains of each layer are
      approximately vertical to tube axis. The disordered-ordered transformation of PE
      chains in each layer is an important structural feature for crystallization of
      confined PE clusters. SWNTs have a considerable effect on the structures and
      stabilities of the confined PE clusters.

PMID- 25605604
TI  - Molecular dynamics study on the tensile deformation of cross-linking epoxy resin.
AB  - Various epoxy resins are used in the electronic industry as encapsulants,
      adhesive, printed wiring boards, electronic packagings, and so on. In this study,
      molecular dynamics method is employed to simulate the tensile deformation of the
      typical electronic epoxy resin. An efficient cross-linking procedure is developed
      to build the molecular model. Based on the cross-linking algorithm, the effects
      of moisture content, cross-linking conversion, strain rate, and temperature on
      the mechanical properties of epoxy resins are investigated. The stress-strain
      curves are plotted. Also the Young's modulus and Poisson ratio are calculated.
      The simulation results are compared with existing experimental data. Good
      agreements are observed. The results show that mechanical properties of epoxy
      resin decrease obviously with increasing moisture content and temperature.
      However the high cross-linking conversion and strain rate enhance the mechanical
      properties of resin. This study is significant to understanding the mechanical
      properties of cross-linking epoxies in high temperature and high humidity. 

PMID- 25605605
TI  - Charge transfer complexes of fullerene[60] with porphyrins as molecular
      rectifiers. A theoretical study.
AB  - Molecular diodes based on charge transfer complexes of fullerene[60] with
      different metalloporphyrins have been modeled. Their current-voltage
      characteristics and the rectification ratios (RR) were calculated using direct ab
      initio method at PBE/def2-SVP level of theory with D3 dispersion correction, for
      voltages ranging from -2 to +2 V. The highest RR of 32.5 was determined for the
      complex of fullerene[60] with zinc tetraphenylporphyrin at 0.8 V. Other molecular
      diodes possessed lower RR, however, all complexes showed RR higher than 1 at all
      bias voltages. The asymmetric evolutions and alignment of the molecular orbitals
      with the applied bias were found to be essential for generating the molecular
      diode rectification behavior. Metal nature of metalloporphyrins and the
      interaction porphyrin-electrode significantly affect RR of molecular diode. Large
      metal ions like Cd(2+) and Ag(2+) in metalloporphyrins disfavor rectification
      creating conducting channels in two directions, while smaller ions Zn(2+) and
      Cu(2+) favor rectification increasing the interaction between gold electrode and
      porphyrin macrocycle.

PMID- 25605606
TI  - Conflict of interest disclosure and the polarisation of scientific communities.
AB  - In this article, we introduce and define the notion of polarised scientific
      communities. We show how polarisation may generate genuine conflicts of interest
      that require specific efforts to be identified and reported, and suggest a simple
      heuristic for the identification and reporting of the polarisation of research.
      We use examples from the debates about breast cancer screening and the
      prescription of statins to people at low risk of heart disease. 

PMID- 25605607
TI  - Why physicians ought not to perform virginity tests.
AB  - In this article I argue that it is not morally justified for physicians to
      perform virginity tests. First, I contend that, on the basis of the principle of
      non-maleficence, physicians should not perform virginity tests, because of the
      potential harms to those who are tested that can result from such tests. Second,
      I highlight some of the social harms that the practice causes, and argue that
      physicians ought not to be complicit in causing these harms. Third, I argue that
      physicians ought not to perform virginity tests on the grounds that testing for
      virginity is scientifically impossible, and physicians are morally obliged to
      practise according to scientific principles. Finally, I contend that an ethically
      sound response to virginity testing requires that the medical profession as a
      whole should follow the example of the Quebec College of Physicians in declaring
      this practice by physicians as unethical. 

PMID- 25605608
TI  - Demise of the LCP: villain or scapegoat?
AB  - The winding down and withdrawal of the Liverpool Care Pathway (LCP) following the
      Neuberger Report has been met with mixed reviews. It appears that responsibility
      for failures of clinical care has been laid at the feet of a care pathway rather
      than the practitioners who used it, a rather curious outcome given that the LCP
      was primarily a system of documentation, a tool with no intrinsic therapeutic
      properties. The Neuberger inquiry was the result of persistent and repeated
      reports of poor-quality end-of-life care associated with the use of the LCP.
      There were indeed problems with the LCP regarding the process of diagnosing dying
      and its approach to supportive care, particularly artificial nutrition and
      hydration. Some of the problems were the product of personal or professional
      ideology influencing goals of care rather than patient-centred considerations.
      These problems were not insurmountable, however, and were being addressed by the
      organisation responsible for the LCP. With the removal of the LCP, we are left
      with no bench mark for end-of-life care, only aspirational goals for
      individualised care plans. It seems unlikely that practitioners who could not
      provide appropriate care with the LCP will do so without it. 

PMID- 25605609
TI  - A cross-sectional survey to investigate community understanding of medical
      research ethics committees.
AB  - Study explanatory forms often state that an ethics committee has approved a
      research project. To determine whether the lay community understand the roles of
      ethics committees in research, we took a cross-sectional national sample from
      three sampling frames: the general population (n=1532); cohort study participants
      (n=397); and case-control study participants (n=151). About half (51.3%) of the
      participants had heard of ethics committees. Those who had were more likely to be
      those who had participated in previous surveys, older participants, those born in
      Australia and those with higher education. Almost all participants agreed that
      the roles of an ethics committee were to protect participants' privacy and ensure
      no harm came to study participants and most agreed that the committee's role was
      to ensure that the research was capable of providing answers. Case-control and
      cohort participants were more likely than the general population to consider that
      the role of an ethics committee was to design the research and obtain research
      funding. Overall, we found that about half of the population are aware of ethics
      committees and that most could correctly identify that ethics committees are
      there to protect the welfare and rights of research participants, although a
      substantial minority had some incorrect beliefs about the committees' roles.
      Increased education, particularly for migrants and older people, might improve
      understanding of the role of ethics committees in research. 

PMID- 25605610
TI  - Oral-specific ablation of Klf4 disrupts epithelial terminal differentiation and
      increases premalignant lesions and carcinomas upon chemical carcinogenesis.
AB  - BACKGROUND: Squamous cell carcinoma (SSC) of the head and neck is the sixth most
      common cancer and is rarely diagnosed in early stages. The transcription factor
      Krupsilonppel-like factor 4 (Klf4) suppresses cell proliferation and promotes
      differentiation. Inducible mice carrying an oral-specific ablation of Klf4 (K14
      CreER(tam) /Klf4(flox/flox) ) develop mild dysplastic lesions and abnormal
      differentiation in the tongue. Aiming to analyze whether Klf4 cooperate in oral
      chemical carcinogenesis,we applied 4-nitroquinoline 1-oxide (4NQO), a tobacco
      surrogate, to this conditional Klf4 knockout mice. METHODS: K14-CreER(tam)
      /Klf4(flox/flox) and control mice were treated with 4NQO for 16 weeks and
      monitored until week 30. Histopathological samples were used for diagnostic
      purposes and immunofluorescence detection of epithelial differentiation markers.
      RESULTS: 4NQO-treated K14-CreER(tam) /Klf4(flox/flox) mice (Klf4KO 4NQO) showed a
      significant weight loss and developed more severe dysplastic lesions than control
      mice with 4NQO (P < 0.005). The Klf4KO 4NQO showed a tendency to higher incidence
      of oral SCC and a marked keratinization pattern in dysplasias, in situ carcinomas
      and SCC. Also, tongues derived from Klf4KO 4NQO mice exhibited reduced terminal
      differentiation as judged by cytokeratin 1 staining when compared with 4NQO
      treated controls. CONCLUSIONS: Klf4 ablation results in more severe dysplastic
      lesions in oral mucosa, with a tendency to higher incidence of SCC, after
      chemical carcinogenesis. We show here, in a context similar to the human
      carcinogenesis, that absence of Klf4 accelerates carcinogenesis and correlates
      with the absence of cytokeratin 1 expression. These results suggest a potential
      role for KLF4 as a tumor suppressor gene for the tongue epithelium.

PMID- 25605611
TI  - Gambling Outcome Expectancies and Gambling Behavior Among African-American
      Adolescents: Gender as a Moderating Variable.
AB  - Most high school adolescents have reported past year gambling, and males gamble
      more frequently and problematically than females. Ethnic minority adolescents
      appear to be gambling at a higher rate than Caucasian adolescents. There is
      evidence indicating that adolescent gambling outcome expectancies are correlated
      with gambling behavior, but limited evidence that this relation differs by
      gender. In the present study gender was evaluated as a moderator in the relation
      between gambling outcome expectancies and gambling behaviors in an African
      American high school sample. Males gambled more frequently, gambled more
      problematically and held more positive gambling outcome expectancies than
      females. Gender was found to moderate the relations between gambling frequency
      and the expectations of material gain, affect, self-evaluation and parental
      approval. Gender also moderated the relations between gambling problems and
      expectations of affect and self-evaluation. These findings should inform future
      adolescent gambling prevention and intervention programs. 

PMID- 25605612
TI  - Psychosocial work characteristics and needle stick and sharps injuries among
      nurses in China: a prospective study.
AB  - PURPOSE: Psychosocial work characteristics may be associated with needle stick
      and sharps injuries (NSIs) among nurses. The current evidence is, however,
      sparse, inconclusive, and mainly limited to cross-sectional investigations. We
      aimed to contribute prospective data. METHODS: We conducted a prospective study
      among 1,791 female hospital nurses from China. At baseline and at a 1-year follow
      up, fourteen psychosocial work characteristics were assessed by the short
      Copenhagen Psychosocial Questionnaire. At follow-up, any NSI in the workplace
      during the previous year was measured by participants' self-reports. We
      quantified associations between (1) psychosocial work characteristics at baseline
      and NSIs at follow-up by multivariate relative risks (Poisson regression) and (2)
      NSIs reported at follow-up with psychosocial work characteristics at follow-up
      (multivariate linear regression, among others, adjusted for psychosocial work
      characteristics at baseline). RESULTS: The only psychosocial work characteristic
      associated with a slightly increased risk of subsequent NSIs was quantitative
      demands. Examining the opposite direction of effect, we found that NSIs during
      the year preceding the follow-up were associated with slightly worse ratings of
      seven psychosocial work characteristics at follow-up (i.e., influence at work,
      meaning of work, commitment to the workplace, quality of leadership, social
      support, social community at work, and job insecurity). CONCLUSIONS: Overall, our
      study does not provide compelling evidence for an association of psychosocial
      work characteristics and subsequent occurrence of NSIs. By contrast, experience
      of NSIs may predict less favorable perceptions of psychosocial work
      characteristics.

PMID- 25605613
TI  - The use of murine-derived fundic organoids in studies of gastric physiology.
AB  - KEY POINTS: An in vitro approach to study gastric development is primary mouse
      derived epithelium cultured as three-dimensional spheroids known as organoids. We
      have devised two unique gastric fundic-derived organoid cultures: model 1 for the
      expansion of gastric fundic stem cells, and model 2 for the maintenance of mature
      cell lineages. Organoids maintained in co-culture with immortalized stomach
      mesenchymal cells express robust numbers of surface pit, mucous neck, chief,
      endocrine and parietal cells. Histamine induced a significant decrease in
      intraluminal pH that was reversed by omeprazole in fundic organoids and indicated
      functional activity and regulation of parietal cells. Localized photodamage
      resulted in rapid cell exfoliation coincident with migration of neighbouring
      cells to the damaged area, sustaining epithelial continuity. We report the use of
      these models for studies of epithelial cell biology and cell damage and repair.
      ABSTRACT: Studies of gastric function and disease have been limited by the lack
      of extended primary cultures of the epithelium. An in vitro approach to study
      gastric development is primary mouse-derived antral epithelium cultured as three
      dimensional spheroids known as organoids. There have been no reports on the use
      of organoids for gastric function. We have devised two unique gastric fundic
      derived organoid cultures: model 1 for the expansion of gastric fundic stem
      cells, and model 2 for the maintenance of mature cell lineages. Both models were
      generated from single glands dissociated from whole fundic tissue and grown in
      basement membrane matrix (Matrigel) and organoid growth medium. Model 1 enriches
      for a stem cell-like niche via simple passage of the organoids. Maintained in
      Matrigel and growth medium, proliferating organoids expressed high levels of stem
      cell markers CD44 and Lgr5. Model 2 is a system of gastric organoids co-cultured
      with immortalized stomach mesenchymal cells (ISMCs). Organoids maintained in co
      culture with ISMCs express robust numbers of surface pit, mucous neck, chief,
      endocrine and parietal cells. Histamine induced a significant decrease in
      intraluminal pH that was reversed by omeprazole in fundic organoids and indicated
      functional activity and regulation of parietal cells. Localized photodamage
      resulted in rapid cell exfoliation coincident with migration of neighbouring
      cells to the damaged area, sustaining epithelial continuity. Thus, we report the
      use of these models for studies of epithelial cell biology and cell damage and
      repair.

PMID- 25605614
TI  - TMEM225: a possible protein phosphatase 1gamma2 (PP1gamma2) regulator localizes
      to the equatorial segment in mouse spermatozoa.
AB  - Tmem225 encodes a putative four-transmembrane domain protein that has an RVxF
      motif, which is known to be a consensus site for interacting with
      serine/threonine protein phosphatase 1 (PP1). We previously identified Tmem225 as
      one of 53 spermatogenesis-associated transmembrane protein genes, with no known
      physiological function. In this study, we investigated the expression and
      molecular characteristics of TMEM225 in mice. Tmem225 production was found to be
      specific to testicular germ cells, with expression increasing during
      spermatogenesis. In mature spermatozoa, TMEM225 is localized to the equatorial
      segment of the acrosome but not to the midpiece or tail. TMEM225 appears to be an
      outer and/or inner acrosomal membrane protein that is lost from the dorsal region
      of the acrosome after the acrosome reaction. TMEM225 interacts with PP1 in vivo,
      and a pull-down assay revealed that the carboxy-terminal region of TMEM225 can
      bind to PP1gamma2, the predominant isoform of PP1 in male germ cells. In
      addition, TMEM225 inhibited PP1gamma2 activity in vitro via its RVxF motif. Our
      results suggest that in mice, TMEM225 is involved in the differentiation and
      function of spermatozoa through the regulation of PP1gamma2 activity, which is
      necessary for normal spermatogenesis as well as spermatozoa capacitation and
      motility.

PMID- 25605616
TI  - Parents' quality of life and family functioning in pediatric organ
      transplantation.
AB  - Solid organ transplantation is an important treatment option for pediatric
      patients in end-stage organ failure. The impact of pediatric organ
      transplantation on parents' quality of life and family functioning has been found
      to be substantial, but findings on this topic have not previously been
      consolidated. Thirty-one studies were selected for analysis after a database
      search on this topic. We present future research questions and suggestions to
      improve clinical practice based on the integration of this knowledge. 

PMID- 25605617
TI  - Update on the management of Candida infections in preterm neonates.
AB  - Invasive fungal infections in preterm neonates in the neonatal intensive care
      unit are predominantly caused by Candida spp, and have a high burden of morbidity
      and mortality. Effective prophylactic strategies have recently become available,
      but the identification of the best possible strategies to manage high-risk
      infants is still a priority. Choice and use of appropriate antifungal drugs needs
      careful assessment of neonatal characteristics, the epidemiology and drug
      pharmacokinetics. Ideally, antifungal drugs for preterm neonates should target
      fungal bio-films, prevent or effectively treat end-organ localisations, be active
      against fluconazole-resistant Candida species, and have reliable safety and
      tolerability profiles. The paper reviews the state-of-the-art in the area of
      neonatal fungal infections, and addresses some open questions related to the best
      possible prophylactic and therapeutic strategies to be implemented in such unique
      patients. 

PMID- 25605618
TI  - Neonatal and early infancy management of prenatally detected hydronephrosis.
AB  - Hydronephrosis discovered during prenatal ultrasound will often resolve
      spontaneously; however, it should be evaluated in the postnatal period in a
      manner commensurate with its risk of renal injury. Early intervention is
      appropriate in cases of bladder outlet obstruction or the severely obstructed
      solitary kidney. In most other cases, it is both safe and reasonable to allow the
      possibility of spontaneous improvement with the intensity of follow-up based on
      the severity of the hydronephrosis. Clinical decision making should be a shared
      process between families and caregivers. 

PMID- 25605615
TI  - Exome sequencing in HFE C282Y homozygous men with extreme phenotypes identifies a
      GNPAT variant associated with severe iron overload.
AB  - To identify polymorphisms associated with variability of iron overload severity
      in HFE-associated hemochromatosis, we performed exome sequencing of DNA from 35
      male HFE C282Y homozygotes with either markedly increased iron stores (n = 22;
      cases) or with normal or mildly increased iron stores (n = 13; controls). The 35
      participants, residents of the United States, Canada, and Australia, reported no
      or light alcohol consumption. Sequencing data included 82,068 single-nucleotide
      variants, and 10,337 genes were tested for a difference between cases and
      controls. A variant in the GNPAT gene showed the most significant association
      with severe iron overload (P = 3 * 10(-6) ; P = 0.033 by the likelihood ratio
      test after correction for multiple comparisons). Sixteen of twenty-two
      participants with severe iron overload had glyceronephosphate O-acyltransferase
      (GNPAT) polymorphism p.D519G (rs11558492; 15 heterozygotes, one homozygote). No
      control participant had this polymorphism. To examine functional consequences of
      GNPAT deficiency, we performed small interfering RNA-based knockdown of GNPAT in
      the human liver-derived cell line, HepG2/C3A. This knockdown resulted in a >17
      fold decrease in expression of the messenger RNA encoding the iron-regulatory
      hormone, hepcidin. CONCLUSION: GNPAT p.D519G is associated with a high-iron
      phenotype in HFE C282Y homozygotes and may participate in hepcidin regulation.

PMID- 25605619
TI  - Accounting for deaths in neonatal trials: is there a correct approach?

PMID- 25605620
TI  - MRI obtained during versus after hypothermia in asphyxiated newborns.
AB  - OBJECTIVE: To assess whether the brain MRI results obtained during hypothermia
      identify the later brain injury observed in asphyxiated newborns after therapy is
      completed. PATIENTS AND METHODS: Asphyxiated newborns treated with hypothermia
      were prospectively enrolled in this study if they had at least one MRI performed
      during hypothermia treatment and then another MRI performed around day 10 of
      life. RESULTS: A total of 129 MRI scans were obtained from 43 asphyxiated
      newborns treated with hypothermia. Sixty per cent developed brain injury; all the
      brain injuries observed on the late scans were already present on day 2-3 of life
      during hypothermia, and the extent of injury was similar between the early and
      late scans. The brain MRI on day 2-3 of life had a sensitivity of 100% (95% CI
      84% to 100%) and a specificity of 100% (95% CI 77% to 100%) to identify the
      presence and extent of later brain injury. CONCLUSIONS: The brain MRIs performed
      during hypothermia already permit an accurate definition of the presence and
      extent of brain injury that later develop in asphyxiated newborns despite
      treatment. These results may have research and clinical implications for the care
      of these newborns.

PMID- 25605621
TI  - Chikungunya viral arthritis in the United States: a mimic of seronegative
      rheumatoid arthritis.
AB  - OBJECTIVE: Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted
      alphavirus that spread to the Caribbean in 2013 and to the US in 2014. CHIKV
      infected patients develop inflammatory arthritis that can persist for months or
      years, but little is known about the rheumatologic and immunologic features of
      CHIKV-related arthritis in humans, particularly as compared to rheumatoid
      arthritis (RA). The purpose of this study was to describe these features in a
      group of 10 American travelers who were nearly simultaneously infected while
      visiting Haiti in June 2014. METHODS: Patient history was obtained and physical
      examination and laboratory tests were performed. All patients with CHIKV-related
      arthritis had detectable levels of anti-CHIKV IgG. Using cytometry by time-of
      flight (CyTOF), we analyzed peripheral blood mononuclear cells in CHIKV-infected
      patients, healthy controls, and patients with untreated, active RA. RESULTS:
      Among 10 CHIKV-infected individuals, 8 developed persistent symmetric
      polyarthritis that met the American College of Rheumatology/European League
      Against Rheumatism 2010 criteria for (seronegative) RA. CyTOF analysis revealed
      that RA and CHIKV-infected patients had greater percentages of activated and
      effector CD4+ and CD8+ T cells than healthy controls. CONCLUSION: In addition to
      similar clinical features, patients with CHIKV infection and patients with RA
      develop very similar peripheral T cell phenotypes. These overlapping clinical and
      immunologic features highlight a need for rheumatologists to consider CHIKV
      infection when evaluating patients with new, symmetric polyarthritis.

PMID- 25605622
TI  - A study of fundamental courses in the great cardiac vein.
AB  - We studied an extremely rare great cardiac vein anomaly in a 65-year-old woman
      during dissection practice at the Akita University School of Medicine (2013). The
      great cardiac vein has two main roots, one accompanied by a left marginal vein
      that pours into the coronary sinus, and the other ascending along the anterior
      interventricular sulcus from the apex, and running over the circumflex branch of
      the left coronary artery. It then runs along the atrial side of the transverse
      sinus of the pericardium, and drains directly into the superior vena cava. No
      anastomosis between these veins was evident. The great cardiac vein might
      originate from two venous systems, one in the posterior wall of the left
      ventricle, and the other running along the anterior interventricular sulcus.
      These venous systems flow in the venous network of the left edge of the coronary
      sulcus. The former venous system always selected the course, which went to the
      coronary sinus in the venous network. The latter system may drain into one of the
      following four courses: the first one contacts the former course; the second
      passes to the transverse sinus of the pericardium and flows to the (right)
      superior vena cava; the third passes between a pulmonary trunk and ascending
      aorta from the dorsum of the pulmonary trunk, turns around in a ventral aspect,
      and then flows into the left superior vena cava; and the fourth flows to the
      anterior cardiac vein. The first of these belongs to the normal great cardiac
      vein, but the others are anomalous. 

PMID- 25605624
TI  - Tin-containing silicates: alkali salts improve methyl lactate yield from sugars.
AB  - This study focuses on increasing the selectivity to methyl lactate from sugars
      using stannosilicates as heterogeneous catalyst. All group I ions are found to
      have a promoting effect on the resulting methyl lactate yield. Besides, the
      alkali ions can be added both during the preparation of the catalyst or directly
      to the solvent mixture to achieve the highest reported yield of methyl lactate
      (ca. 75 %) from sucrose at 170  degrees C in methanol. The beneficial effect of
      adding alkali to the reaction media applies not only to highly defect-free Sn
      Beta prepared through the fluoride route, but also to materials prepared by post
      treatment of dealuminated commercial Beta zeolites, as well as ordered mesoporous
      stannosilicates, in this case Sn-MCM-41 and Sn-SBA-15. These findings open the
      door to the possibility of using other preparation methods or different Sn
      containing silicates with equally high methyl lactate yields as Sn-Beta. 

PMID- 25605623
TI  - Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids 
      building units for peptidic foldamers.
AB  - Peptidic foldamers have recently emerged as a novel class of artificial oligomers
      with properties and structural diversity similar to that of natural peptides, but
      possessing additional interesting features granting them great potential for
      applications in fields from nanotechnology to pharmaceuticals. Among these,
      foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily
      prepared via the Cu- and Ru-catalyzed click reactions and may offer increased
      side chain variation, but their structural capabilities have not yet been widely
      explored. We here describe a systematic analysis of the conformational space of
      the two most important basic units, the 1,4-substitued (4Tzl) and the 1,5
      substitued (5Tzl) 1,2,3-triazole amino acids, using quantum chemical calculations
      and NMR spectroscopy. Possible conformations of the two triazoles were scanned
      and their potential minima were located using several theoretical approaches
      (B3LYP/6-311++G(2d,2p), omegaB97X-D/6-311++G(2d,2p), M06-2X/6-311++G(2d,2p) and
      MP2/6-311++G(2d,2p)) in different solvents. BOC-protected versions of 4Tzl and
      5Tzl were also prepared via one step transformations and analyzed by 2D NOESY
      NMR. Theoretical results show 9 conformers for 5Tzl derivatives with relative
      energies lying close to each other, which may lead to a great structural
      diversity. NMR analysis also indicates that conformers preferring turn, helix and
      zig-zag secondary structures may coexist in solution. In contrast, 4Tzl has a
      much lower number of conformers, only 4, and these lack strong intraresidual
      interactions. This is again supported by NMR suggesting the presence of both
      extended and bent conformers. The structural information provided on these
      building units could be employed in future design of triazole foldamers. 

PMID- 25605625
TI  - Variation in hospital caesarean section rates and obstetric outcomes among
      nulliparae at term: a population-based cohort study.
AB  - OBJECTIVE: To explore the variation in hospital caesarean section (CS) rates for
      nulliparous women, to determine whether different case-mix, labour and delivery,
      and hospital factors can explain this variation and to examine the association
      between hospital CS rates and outcomes. DESIGN: Population-based cohort study.
      SETTING: New South Wales, 2009-2010. POPULATION: Nulliparous women with singleton
      cephalic live births at term. METHODS: Random effect multilevel logistic
      regression models using linked hospital discharge and birth data. MAIN OUTCOME
      MEASURES: Prelabour and intrapartum CS rates following spontaneous labour or
      labour induction; maternal and neonatal severe morbidity rates. RESULTS: Of 67
      239 nulliparous women, 4902 (7.3%) had a prelabour CS, 39 049 (58.1%) laboured
      spontaneously, and 23 288 (34.6%) had labour induced. Overall, there were 18 875
      (28.1%) CSs, with labour inductions twice as likely to result in an intrapartum
      CS compared with women with a spontaneous onset of labour (34.0% versus 15.5%).
      After adjusting for differences in case-mix, labour and delivery, and hospital
      factors, the overall variation in CS rates decreased by 78% for prelabour CSs,
      52% for intrapartum CSs following spontaneous labour and 9% following labour
      induction. Adjusting for labour and delivery practices increased the unexplained
      variation in intrapartum CSs. The adjusted rates of severe maternal and neonatal
      morbidity were not significantly different across CS rate quintile groups, except
      for women in spontaneous labour, where the hospitals in the lowest CS quintile
      had the lowest neonatal morbidity rate. CONCLUSIONS: Differences in clinical
      practice were substantial contributors to variation in intrapartum CS rates. Our
      findings suggest that CS rates in some hospitals could be lowered without
      adversely affect pregnancy outcomes.

PMID- 25605627
TI  - Functional recordings from awake, behaving rodents through a microchannel based
      regenerative neural interface.
AB  - OBJECTIVE: Neural interface technologies could provide controlling connections
      between the nervous system and external technologies, such as limb prosthetics.
      The recording of efferent, motor potentials is a critical requirement for a
      peripheral neural interface, as these signals represent the user-generated neural
      output intended to drive external devices. Our objective was to evaluate
      structural and functional neural regeneration through a microchannel neural
      interface and to characterize potentials recorded from electrodes placed within
      the microchannels in awake and behaving animals. APPROACH: Female rats were
      implanted with muscle EMG electrodes and, following unilateral sciatic nerve
      transection, the cut nerve was repaired either across a microchannel neural
      interface or with end-to-end surgical repair. During a 13 week recovery period,
      direct muscle responses to nerve stimulation proximal to the transection were
      monitored weekly. In two rats repaired with the neural interface, four wire
      electrodes were embedded in the microchannels and recordings were obtained within
      microchannels during proximal stimulation experiments and treadmill locomotion.
      MAIN RESULTS: In these proof-of-principle experiments, we found that axons from
      cut nerves were capable of functional reinnervation of distal muscle targets,
      whether regenerating through a microchannel device or after direct end-to-end
      repair. Discrete stimulation-evoked and volitional potentials were recorded
      within interface microchannels in a small group of awake and behaving animals and
      their firing patterns correlated directly with intramuscular recordings during
      locomotion. Of 38 potentials extracted, 19 were identified as motor axons
      reinnervating tibialis anterior or soleus muscles using spike triggered
      averaging. SIGNIFICANCE: These results are evidence for motor axon regeneration
      through microchannels and are the first report of in vivo recordings from
      regenerated motor axons within microchannels in a small group of awake and
      behaving animals. These unique findings provide preliminary evidence that
      efferent, volitional motor potentials can be recorded from the microchannel-based
      peripheral neural interface; a critical requirement for any neural interface
      intended to facilitate direct neural control of external technologies.

PMID- 25605626
TI  - Evidence-based guidelines for the management of large hemispheric infarction : a
      statement for health care professionals from the Neurocritical Care Society and
      the German Society for Neuro-intensive Care and Emergency Medicine.
AB  - Large hemispheric infarction (LHI), also known as malignant middle cerebral
      infarction, is a devastating disease associated with significant disability and
      mortality. Clinicians and family members are often faced with a paucity of high
      quality clinical data as they attempt to determine the most appropriate course of
      treatment for patients with LHI, and current stroke guidelines do not provide a
      detailed approach regarding the day-to-day management of these complicated
      patients. To address this need, the Neurocritical Care Society organized an
      international multidisciplinary consensus conference on the critical care
      management of LHI. Experts from neurocritical care, neurosurgery, neurology,
      interventional neuroradiology, and neuroanesthesiology from Europe and North
      America were recruited based on their publications and expertise. The panel
      devised a series of clinical questions related to LHI, and assessed the quality
      of data related to these questions using the Grading of Recommendation
      Assessment, Development and Evaluation guideline system. They then developed
      recommendations (denoted as strong or weak) based on the quality of the evidence,
      as well as the balance of benefits and harms of the studied interventions, the
      values and preferences of patients, and resource considerations. 

PMID- 25605628
TI  - Ten-year follow-up results of a randomized clinical trial comparing left
      thoracoabdominal and abdominal transhiatal approaches to total gastrectomy for
      adenocarcinoma of the oesophagogastric junction or gastric cardia.
AB  - BACKGROUND: The optimal surgical approach for treatment of oesophagogastric
      junction (OGJ) cancer is controversial. A randomized clinical trial (JCOG9502)
      comparing transhiatal (TH) and left thoracoabdominal (LTA) approaches was stopped
      after the first interim analysis owing to limited efficacy for LTA resections.
      Complete 10-year follow-up data are now available. METHODS: Patients with
      histologically proven adenocarcinoma of the OGJ or gastric cardia with
      oesophageal invasion of 3 cm or less were randomized to a TH or LTA approach.
      Both groups underwent total gastrectomy and splenectomy with D2 nodal dissection
      plus para-aortic lymphadenectomy above the left renal vein. For LTA, a thorough
      mediastinal lymphadenectomy below the left inferior pulmonary vein was also
      mandatory. The primary endpoint was overall survival. RESULTS: A total of 167
      patients (82 TH, 85 LTA) were enrolled. The 10-year overall survival rate was 37
      (95 per cent c.i. 26 to 47) per cent for the TH approach and 24 (15 to 34) per
      cent for the LTA technique (P = 0.060). The hazard ratio for death was 1.42 (0.98
      to 2.05) for the LTA technique. Subgroup analysis based on the Siewert
      classification indicated non-significant survival advantages in favour of the TH
      approach. CONCLUSION: LTA resections should be avoided in the treatment of
      adenocarcinoma of the OGJ or gastric cardia. REGISTRATION NUMBER: NCT00149266
      (https://www.clinicaltrials.gov).

PMID- 25605629
TI  - The impact of surgical timing and intervention on outcome in traumatized dogs and
      cats.
AB  - OBJECTIVE: To review the relevant human and veterinary literature regarding the
      timing of surgical intervention for trauma patients and the impact on outcome.
      DATA SOURCES: Original research, clinical studies, and review articles with no
      date restrictions from both human and veterinary literature. HUMAN DATA
      SYNTHESIS: Despite extensive research into the ideal timing of surgical
      intervention for human trauma victims, debate is ongoing and views are still
      evolving. Prior to the 1970s, the standard of care consisted of delayed surgical
      treatment, as these patients were considered too ill to undergo surgery.
      Beginning in the 1970s, and continuing for nearly 2 decades, early definitive
      surgical treatment was recommended. The most recent evolution of human trauma
      management incorporates the concept of damage control surgery, which acknowledges
      the importance of early skeletal stabilization or laparotomy for reducing
      morbidity while attempting to avoid complications such as acute respiratory
      distress syndrome or multiple organ dysfunction syndrome. VETERINARY DATA
      SYNTHESIS: Despite a relatively large amount of literature available regarding
      veterinary trauma, no evidence exists to provide the clinician guidance as to the
      ideal timing of surgery for trauma patients. With the exception of diaphragmatic
      hernia, no studies were identified that attempted to evaluate this variable.
      CONCLUSIONS: Veterinary-specific studies are needed to evaluate the impact of
      surgical timing on outcome following trauma. The information that can be obtained
      from studies in this area can improve veterinary trauma care and may be used as
      models for human trauma care through translational applications.

PMID- 25605630
TI  - The genetic classification of pancreatic neoplasia.
AB  - Cancer is caused by the accumulation of inherited and/or acquired alterations in
      specific genes. The recent decline in the cost of DNA sequencing has allowed
      tumor sequencing to be conducted on a large scale, which, in turn, has led to an
      unprecedented understanding of the genetic events that drive neoplasia. This
      understanding, when integrated with meticulous histologic analyses and with
      clinical findings, has direct clinical implications. The recent sequencing of all
      of the major types of cystic and noncystic neoplasms of the pancreas has revealed
      opportunities for molecular diagnoses and for personalized treatment. This review
      summarizes the results from these recent studies focusing on the clinical
      relevance of genomic data. 

PMID- 25605632
TI  - Use of Accelerometer-Based Feedback of Walking Activity for Appraising Progress
      With Walking-Related Goals in Inpatient Stroke Rehabilitation: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Regaining independent ambulation is important to those with stroke.
      Increased walking practice during "down time" in rehabilitation could improve
      walking function for individuals with stroke. OBJECTIVE: To determine the effect
      of providing physiotherapists with accelerometer-based feedback on patient
      activity and walking-related goals during inpatient stroke rehabilitation.
      METHODS: Participants with stroke wore accelerometers around both ankles every
      weekday during inpatient rehabilitation. Participants were randomly assigned to
      receive daily feedback about walking activity via their physiotherapists (n = 29)
      or to receive no feedback (n = 28). Changes in measures of daily walking (walking
      time, number of steps, average cadence, longest bout duration, and number of
      "long" walking bouts) and changes in gait control and function assessed in
      laboratory were compared between groups. RESULTS: There was no significant
      increase in walking time, number of steps, longest bout duration, or number of
      long walking bouts for the feedback group compared with the control group (P
      values > .20). However, individuals who received feedback significantly increased
      cadence of daily walking more than the control group (P = .013). From the in
      laboratory gait assessment, individuals who received feedback had a greater
      increase in walking speed and decrease in step time variability than the control
      group (P values < .030). CONCLUSION: Feedback did not increase the amount of
      walking completed by individuals with stroke. However, there was a significant
      increase in cadence, indicating that intensity of daily walking was greater for
      those who received feedback than the control group. Additionally, more intense
      daily walking activity appeared to translate to greater improvements in walking
      speed.

PMID- 25605633
TI  - Muscle Fatigability During a Sustained Index Finger Abduction and Depression
      Scores Are Associated With Perceived Fatigue in Patients With Relapsing-Remitting
      Multiple Sclerosis.
AB  - INTRODUCTION: Fatigue is a common and debilitating symptom in patients with
      multiple sclerosis (MS). Self-reported levels of perceived fatigue are associated
      with both patient characteristics and clinical measures. Pilot analysis indicated
      that muscle fatigability combined with depression scores was highly associated
      with perceived fatigue in patients with MS. Studies that combine physiological
      and psychological constructs to explain MS-related fatigue are scarce. Therefore,
      the present study aimed to evaluate the robustness of the association between
      perceived fatigue, muscle fatigability, and depression scores in MS. METHODS:
      Eighty-six patients with relapsing-remitting MS completed 2 fatigue
      questionnaires (Fatigue Severity Scale [FSS] and Modified Fatigue Impact Scale
      [MFIS]) and a depression questionnaire (Hospital Anxiety and Depression Scale
      [HADS]). Maximal index finger abduction force (maximum voluntary contraction
      [MVC]) was measured, as well as muscle fatigability during a 2-minutes sustained
      maximal contraction. Multivariable regression analyses were used to analyze the
      association between perceived fatigue, and muscle fatigability and depression
      scores. RESULTS: Perceived fatigue was associated with depression, muscle
      fatigability, and, depending on the questionnaire, to sex or to MVC. The model
      explained 40% and 48% of the variation in perception of fatigue as indexed with
      FSS questionnaire (r(partial): HADS 0.45, muscle fatigability 0.45, MVC -0.14,
      sex 0.32), and MFIS physical questionnaire (r(partial): HADS 0.59, muscle
      fatigability 0.49, MVC -0.38), respectively. CONCLUSIONS: The found association
      accentuates the importance of including both physiological fatigability-related
      and psychological mood-related constructs in models to explain perceived fatigue
      in patients with MS. The model also directs future research toward applying
      effortful conditions and emphasizes the importance of assessing different
      constructs when evaluating rehabilitation strategies to reduce MS-related
      fatigue.

PMID- 25605635
TI  - Sugar-sensitive neurone responses and sugar feeding preferences influence
      lifespan and biting behaviours of the Afrotropical malaria mosquito, Anopheles
      gambiae.
AB  - Floral nectar is the main source of carbohydrates for many insects including
      mosquitoes. Nonetheless, the physiological mechanisms underlying feeding on
      carbohydrates by the Afrotropical malaria mosquito Anopheles gambiae remain
      poorly understood. Here, we tested whether sugar sensitivity and sugar feeding
      preferences correlate with longevity in A. gambiae. We also tested whether
      feeding females on different sugar diets influences their biting behaviours.
      Electrophysiological recordings show that sugar neurones on the labella of
      females are most sensitive to sucrose, mixtures of glucose and fructose, and to
      melezitose; other sugars tested, including glucose and fructose presented alone,
      only weakly activate these taste neurones. Mosquitoes survive longest on sucrose,
      the most preferred sugar. Whereas feeding on a mixture of glucose and fructose is
      preferred over fructose or glucose alone, fructose supports higher longevity than
      either glucose or the mixture of the two hexoses. Females that had previously fed
      on glucose show a stronger biting response than those fed on sucrose, perhaps in
      an effort to compensate for their lower energetic state. These findings
      contribute to our understanding of the physiological basis of sugar feeding in A.
      gambiae and indicate how the sugar diet can affect laboratory-reared A. gambiae
      biting behaviours. 

PMID- 25605636
TI  - Valproic acid-induced hepatotoxicity in Alpers syndrome is associated with
      mitochondrial permeability transition pore opening-dependent apoptotic
      sensitivity in an induced pluripotent stem cell model.
AB  - Valproic acid (VPA) is widely used to treat epilepsy, migraine, chronic headache,
      bipolar disorder, and as adjuvant chemotherapy, but potentially causes
      idiosyncratic liver injury. Alpers-Huttenlocher syndrome (AHS), a neurometabolic
      disorder caused by mutations in mitochondrial DNA polymerase gamma (POLG), is
      associated with an increased risk of developing fatal VPA hepatotoxicity.
      However, the mechanistic link of this clinical mystery remains unknown. Here,
      fibroblasts from 2 AHS patients were reprogrammed to induced pluripotent stem
      cells (iPSCs) and then differentiated to hepatocyte-like cells (AHS iPSCs-Hep).
      Both AHS iPSCs-Hep are more sensitive to VPA-induced mitochondrial-dependent
      apoptosis than controls, showing more activated caspase-9 and cytochrome c
      release. Strikingly, levels of both soluble and oligomeric optic atrophy 1, which
      together keep cristae junctions tight, are reduced in AHS iPSCs-Hep. Furthermore,
      POLG mutation cells show reduced POLG expression, mitochondrial DNA (mtDNA)
      amount, mitochondrial adenosine triphosphate production, as well as abnormal
      mitochondrial ultrastructure after differentiation to hepatocyte-like cells.
      Superoxide flashes, spontaneous bursts of superoxide generation, caused by
      opening of the mitochondrial permeability transition pore (mPTP), occur more
      frequently in AHS iPSCs-Hep. Moreover, the mPTP inhibitor, cyclosporine A,
      rescues VPA-induced apoptotic sensitivity in AHS iPSCs-Hep. This result suggests
      that targeting mPTP opening could be an effective method to prevent
      hepatotoxicity by VPA in AHS patients. In addition, carnitine or N
      acetylcysteine, which has been used in the treatment of VPA-induced
      hepatotoxicity, is able to rescue VPA-induced apoptotic sensitivity in AHS iPSCs
      Hep. CONCLUSION: AHS iPSCs-Hep are more sensitive to the VPA-induced
      mitochondrial-dependent apoptotic pathway, and this effect is mediated by mPTP
      opening. Toxicity models in genetic diseases using iPSCs enable the evaluation of
      drugs for therapeutic targets.

PMID- 25605631
TI  - Clinical observations on chemotherapy curable malignancies: unique genetic
      events, frozen development and enduring apoptotic potential.
AB  - BACKGROUND: A select number of relatively rare metastatic malignancies comprising
      trophoblast tumours, the rare childhood cancers, germ cells tumours, leukemias
      and lymphomas have been routinely curable with chemotherapy for more than 30
      years. However for the more common metastatic malignancies chemotherapy treatment
      frequently brings clinical benefits but cure is not expected. Clinically this
      clear divide in outcome between the tumour types can appear at odds with the
      classical theories of chemotherapy sensitivity and resistance that include rates
      of proliferation, genetic development of drug resistance and drug efflux pumps.
      We have looked at the clinical characteristics of the chemotherapy curable
      malignancies to see if they have any common factors that could explain this
      extreme differential sensitivity to chemotherapy. DISCUSSION: It has previously
      been noted how the onset of malignancy can leave malignant cells fixed with some
      key cellular functions remaining frozen at the point in development at which
      malignant transformation occurred. In the chemotherapy curable malignancies the
      onset of malignancy is in each case closely linked to one of the unique genetic
      events of; nuclear fusion for molar pregnancies, choriocarcinoma and placental
      site trophoblast tumours, gastrulation for the childhood cancers, meiosis for
      testicular cancer and ovarian germ cell tumours and VDJ rearrangement and somatic
      hypermutation for acute leukemia and lymphoma. These processes are all linked to
      natural periods of supra-physiological apoptotic potential and it appears that
      the malignant cells arising from them usually retain this heightened sensitivity
      to DNA damage. To investigate this hypothesis we have examined the natural
      history of the healthy cells during these processes and the chemotherapy
      sensitivity of malignancies arising before, during and after the events. To add
      to the debate on chemotherapy resistance and sensitivity, we would argue that
      malignancies can be functionally divided into 2 groups. Firstly those that arise
      in cells with naturally heightened apoptotic potential as a result of their
      proximity to the unique genetic events, where the malignancies are generally
      chemotherapy curable and then the more common malignancies that arise in cells of
      standard apoptotic potential that are not curable with classical cytotoxic drugs.

PMID- 25605637
TI  - Assessment of cognitive impairment: the Holy Grail of risk prediction?

PMID- 25605638
TI  - Training the left ventricle with preserved ejection fraction or cardiorespiratory
      fitness? Rocking the boat.

PMID- 25605639
TI  - Exercise training as therapy for heart failure: current status and future
      directions.

PMID- 25605641
TI  - Left ventricular assist device outflow cannula obstruction treated with
      percutaneous endovascular stenting.

PMID- 25605640
TI  - Nitrate's effect on activity tolerance in heart failure with preserved ejection
      fraction trial: rationale and design.

PMID- 25605644
TI  - Programming and regulation of metabolic homeostasis.
AB  - Evidence is presented that the rate and equilibrium constants in mitochondrial
      oxidative phosphorylation set and maintain metabolic homeostasis in eukaryotic
      cells. These internal constants determine the energy state ([ATP]/[ADP][Pi]), and
      the energy state maintains homeostasis through a bidirectional sensory/signaling
      control network that reaches every aspect of cellular metabolism. The energy
      state is maintained with high precision (to ~1 part in 10(10)), and the control
      system can respond to transient changes in energy demand (ATP utilization) of
      more than 100 times the resting rate. Epigenetic and environmental factors are
      able to "fine-tune" the programmed set point over a narrow range to meet the
      special needs associated with cell differentiation and chronic changes in
      metabolic requirements. The result is robust across-platform control of
      metabolism, which is essential to cellular differentiation and the evolution of
      complex organisms. A model of oxidative phosphorylation is presented, for which
      the steady-state rate expression has been derived and computer programmed. The
      behavior of oxidative phosphorylation predicted by the model is shown to fit the
      experimental data available for isolated mitochondria as well as for cells and
      tissues. This includes measurements from several different mammalian tissues as
      well as from insect flight muscle and plants. The respiratory chain and oxidative
      phosphorylation is remarkably similar for all higher plants and animals. This is
      consistent with the efficient synthesis of ATP and precise control of metabolic
      homeostasis provided by oxidative phosphorylation being a key to cellular
      differentiation and the evolution of structures with specialized function. 

PMID- 25605643
TI  - Resistance exercise-induced S6K1 kinase activity is not inhibited in human
      skeletal muscle despite prior activation of AMPK by high-intensity interval
      cycling.
AB  - Combining endurance and strength training in the same session has been reported
      to reduce the anabolic response to the latter form of exercise. The underlying
      mechanism, based primarily on results from rodent muscle, is proposed to involve
      AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in
      eight trained male subjects who in randomized order performed either resistance
      exercise only (R) or interval cycling followed by resistance exercise (ER).
      Biopsies taken from the vastus lateralis before and after endurance exercise and
      repeatedly after resistance exercise were assessed for glycogen content, kinase
      activity, protein phosphorylation, and gene expression. Mixed muscle fractional
      synthetic rate was measured at rest and during 3 h of recovery using the stable
      isotope technique. In ER, AMPK activity was elevated immediately after both
      endurance and resistance exercise (~90%, P < 0.05) but was unchanged in R.
      Thr(389) phosphorylation of S6K1 was increased severalfold immediately after
      exercise (P < 0.05) in both trials and increased further throughout recovery.
      After 90 and 180 min recovery, S6K1 activity was elevated (~55 and ~110%,
      respectively, P < 0.05) and eukaryotic elongation factor 2 phosphorylation was
      reduced (~55%, P < 0.05) with no difference between trials. In contrast, markers
      for protein catabolism were differently influenced by the two modes of exercise;
      ER induced a significant increase in gene and protein expression of MuRF1 (P <
      0.05), which was not observed following R exercise only. In conclusion, cycling
      induced elevation in AMPK activity does not inhibit mTOR complex 1 signaling
      after subsequent resistance exercise but may instead interfere with the
      hypertrophic response by influencing key components in protein breakdown. 

PMID- 25605642
TI  - Arbitration between Action Strategies in Obsessive-Compulsive Disorder.
AB  - Decision making in a complex world, characterized both by predictable
      regularities and by frequent departures from the norm, requires dynamic switching
      between rapid habit-like, automatic processes and slower, more flexible
      evaluative processes. These strategies, formalized as "model-free" and "model
      based" reinforcement learning algorithms, respectively, can lead to divergent
      behavioral outcomes, requiring a mechanism to arbitrate between them in a context
      appropriate manner. Recent data suggest that individuals with obsessive
      compulsive disorder (OCD) rely excessively on inflexible habit-like decision
      making during reinforcement-driven learning. We propose that inflexible reliance
      on habit in OCD may reflect a functional weakness in the mechanism for context
      appropriate dynamic arbitration between model-free and model-based decision
      making. Support for this hypothesis derives from emerging functional imaging
      findings. A deficit in arbitration in OCD may help reconcile evidence for
      excessive reliance on habit in rewarded learning tasks with an older literature
      suggesting inappropriate recruitment of circuitry associated with model-based
      decision making in unreinforced procedural learning. The hypothesized deficit and
      corresponding circuitry may be a particularly fruitful target for interventions,
      including cognitive remediation. 

PMID- 25605645
TI  - Leiomyoma cutis: a focused review on presentation, management, and association
      with malignancy.
AB  - Cutaneous leiomyomas (CLs) are rare, sporadic, or inherited tumors of smooth
      muscle origin associated with various disorders. Hereditary leiomyomatosis and
      renal cell cancer (HLRCC) is the primary tumor predisposition syndrome associated
      with inherited CLs, affecting 180 families worldwide, with significant mortality.
      CLs are subdivided into piloleiomyomas, genital leiomyomas, and angioleiomyomas
      based on their smooth muscle of origin, as well as their clinicopathologic
      features. Piloleiomyomas, derived from arrector pili muscle, are solitary or
      multiple firm papulonodules located typically on the extremities and trunk;
      genital leiomyomas, derived from dartoic, vulvar, or mammary smooth muscle, are
      solitary papulonodules or pedunculated papules located on the scrotum, vulva, or
      nipple; and angioleiomyomas, which include solid, cavernous, or venous subtypes,
      are derived from the tunica media of small arteries and veins and typically
      present on the extremities. Partial/excisional biopsy is required for diagnosing
      all CLs. Histology shows interlacing fascicles of spindle cells with moderate
      amounts of eosinophilic cytoplasm and a blunt-ended, elongated nucleus with
      perinuclear halos. Surgical excision is curative for CLs, with other management
      options including medical or destructive therapy; active surveillance is advised
      to monitor HLRCC-associated neoplasms, with pharmacological therapies under
      active research. 

PMID- 25605646
TI  - Trends in the Use of the GreenLight Laser in the Surgical Management of Benign
      Prostatic Obstruction in France Over the Past 10 Years.

PMID- 25605647
TI  - Regioselective oxidative Pd-catalysed coupling of alkylboronic acids with pyridin
      2-yl-substituted heterocycles.
AB  - A total of 19 alkylated heterocycles (thiophenes, benzothiophenes, pyrroles,
      furans) were prepared (36-99% yield) from the respective pyridin-2-yl-substituted
      precursors employing alkylboronic acids as the C-H alkylating reagents in an
      oxidative (Ag2CO3 and 2,6-dimethyl-1,4-benzoquinone as oxidants) Pd-catalysed
      coupling reaction. 

PMID- 25605648
TI  - Not to forget portal cavernoma cholangiopathy: the great mimicker!

PMID- 25605650
TI  - CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease.
AB  - RATIONALE: Kawasaki disease (KD), an acute febrile vasculitis, is the most common
      cause of acquired heart disease in childhood; however, diagnosing KD can be
      difficult. OBJECTIVE: To identify unique proteomic biomarkers that can be used to
      facilitate earlier diagnosis of KD. METHODS AND RESULTS: We enrolled 214 children
      with fever and clinical features suggestive of KD. Of those, only 100 were
      diagnosed with KD. Their plasma samples were globally analyzed for cytokines,
      chemokines, and cell adhesion molecules using an unbiased, large-scale,
      quantitative protein array. This study was conducted in 3 stages: discovery,
      replication, and blinded validation. During the discovery phase (n [KD]=37; n
      [control]=20), the expression of interleukin-17F, sCD40L, E-selectin, CCL23
      (myeloid progenitor inhibitory factor 1), and CXCL10 (IFN-gamma-inducible protein
      10 [IP-10]) were upregulated during the acute phase in patients with KD when
      compared with that in the controls. A notable increase was observed in the IP-10
      levels (KD, 3037 +/- 226.7 pg/mL; control, 672 +/- 130.4 pg/mL; P=4.1 * 10(-11)).
      Receiver-operating characteristic analysis of the combined discovery and
      replication data (n [KD]=77; n [control]=77) showed that the IP-10 level had high
      area under the curve values (0.94 [95% confidence interval, 0.9055-0.9778];
      sensitivity, 100%; and specificity, 77%). With 1318 pg/mL as the optimal cutoff,
      the blinded validation study confirmed that the IP-10 levels were a good
      predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels
      returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the
      T cells of patients with acute KD. CONCLUSIONS: IP-10 may be used as a biomarker
      to facilitate KD diagnosis, and it may provide clues about the pathogenesis of
      KD.

PMID- 25605651
TI  - "Grappling to think clearly": vernacular theorizing in Robbie McCauley's Sugar.
AB  - This article examines Robbie McCauley's Sugar, focusing on how this solo
      performance work opens up discursive spaces for a range of voices and
      perspectives. I argue that the ideas expressed in Sugar work as a type of
      vernacular theorizing, questioning the means by which certain perspectives and
      ways of knowing are valued over others. In the conclusion, I suggest how Sugar
      could serve as a model for health professionals involved in the fight again
      diabetes, as it opens up opportunities for dialogue and makes visible the
      processual nature of people's attempts to make sense of the disease. 

PMID- 25605649
TI  - Mitochondrial reprogramming induced by CaMKIIdelta mediates hypertrophy
      decompensation.
AB  - RATIONALE: Sustained activation of Galphaq transgenic (Gq) signaling during
      pressure overload causes cardiac hypertrophy that ultimately progresses to
      dilated cardiomyopathy. The molecular events that drive hypertrophy
      decompensation are incompletely understood. Ca(2+)/calmodulin-dependent protein
      kinase II delta (CaMKIIdelta) is activated downstream of Gq, and overexpression
      of Gq and CaMKIIdelta recapitulates hypertrophy decompensation. OBJECTIVE: To
      determine whether CaMKIIdelta contributes to hypertrophy decompensation provoked
      by Gq. METHODS AND RESULTS: Compared with Gq mice, compound Gq/CaMKIIdelta
      knockout mice developed a similar degree of cardiac hypertrophy but exhibited
      significantly improved left ventricular function, less cardiac fibrosis and
      cardiomyocyte apoptosis, and fewer ventricular arrhythmias. Markers of oxidative
      stress were elevated in mitochondria from Gq versus wild-type mice and
      respiratory rates were lower; these changes in mitochondrial function were
      restored by CaMKIIdelta deletion. Gq-mediated increases in mitochondrial
      oxidative stress, compromised membrane potential, and cell death were
      recapitulated in neonatal rat ventricular myocytes infected with constitutively
      active Gq and attenuated by CaMKII inhibition. Deep RNA sequencing revealed
      altered expression of 41 mitochondrial genes in Gq hearts, with normalization of
      ~40% of these genes by CaMKIIdelta deletion. Uncoupling protein 3 was markedly
      downregulated in Gq or by Gq expression in neonatal rat ventricular myocytes and
      reversed by CaMKIIdelta deletion or inhibition, as was peroxisome proliferator
      activated receptor alpha. The protective effects of CaMKIIdelta inhibition on
      reactive oxygen species generation and cell death were abrogated by knock down of
      uncoupling protein 3. Conversely, restoration of uncoupling protein 3 expression
      attenuated reactive oxygen species generation and cell death induced by
      CaMKIIdelta. Our in vivo studies further demonstrated that pressure overload
      induced decreases in peroxisome proliferator-activated receptor alpha and
      uncoupling protein 3, increases in mitochondrial protein oxidation, and
      hypertrophy decompensation, which were attenuated by CaMKIIdelta deletion.
      CONCLUSIONS: Mitochondrial gene reprogramming induced by CaMKIIdelta emerges as
      an important mechanism contributing to mitotoxicity in decompensating
      hypertrophy.

PMID- 25605652
TI  - Engaging for-profit providers in TB control: lessons learnt from initiatives in
      South Asia.
AB  - There has been a huge expansion in the private health-care sector over the past
      two decades, particularly in South Asia, resulting in over 80% of patients
      seeking care from private health providers. Despite concerns about the quality
      and equity of private sector service provision, most government public health
      bodies recognize that the private sector reaches individuals that public
      institutions cannot cater to, thereby being important in moving closer to
      universal health coverage. Numerous initiatives have been launched and are being
      planned to involve private practitioners in effectively diagnosing, reporting and
      managing infectious diseases such as tuberculosis. However, there is a notable
      dearth of papers discussing which elements of private sector engagement
      strategies are more or less successful and the ethical issues that arise when
      engagement strategies are operationalized. This article brings together the
      authors' experiences of working on projects to engage private allopathic health
      providers in Pakistan, Bangladesh and India for improved tuberculosis control.
      Motivations of and strategies required to engage private allopathic heath
      providers, specifically doctors, diagnostic laboratories and pharmacies, and some
      of the ethical issues that arise when designing programmes for engagement are
      discussed. 

PMID- 25605653
TI  - Characterization of Leptospira infection in suckling and weaning rat pups.
AB  - Rats are known to be the most important reservoirs of Leptospira spp. However,
      the leptospiral dose and age at which rats become resistant to Leptospira
      infection are not yet well elucidated. Aimed to characterize leptospirosis in rat
      pups, we found that suckling pups (4-, 7-, and 14-day old) are susceptible to
      leptospires and resistance starts from the weaning age (23-day old).
      Susceptibility of rat pups was also affected by the infecting dose of the
      organisms. Jaundice, decrease in body weight, and neurological symptoms prior to
      moribundity was evident in infected suckling pups. However, 23-day-old infected
      pups did not manifest any pathological changes and were able to survive the
      infection similar to adult rats. Based on these results, we propose the suckling
      rat pup as a novel animal model of human leptospirosis to investigate
      pathogenesis, development of host resistance, and the mechanisms involved in rats
      becoming maintenance hosts for leptospires. 

PMID- 25605654
TI  - Systemic inflammatory response syndrome after transcatheter or surgical aortic
      valve replacement.
AB  - OBJECTIVE: An inflammatory response after cardiac surgery is associated with
      worse clinical outcomes, but recent trials to attenuate it have been neutral. We
      evaluated the association between systemic inflammatory response syndrome (SIRS)
      and mortality after transcatheter (TAVR) and surgical aortic valve replacement
      (SAVR) for aortic stenosis (AS) and evaluated whether diabetes influenced this
      relationship. METHODS: Patients (n=747) with severe AS treated with TAVR (n=264)
      or SAVR (n=483) between January 2008 and December 2013 were included and 37% had
      diabetes mellitus. SIRS was defined by four criteria 12-48 h after aortic valve
      replacement (AVR): (1) white blood cell count <4 or >12; (2) heart rate >90; (3)
      temperature <36 or >38 degrees C; or (4) respiratory rate >20. Severe SIRS was
      defined as meeting all four criteria. The primary endpoint was 6-month all-cause
      mortality (60 deaths occurred by 6 months). Inverse probability weighting (IPW)
      was performed on 44 baseline and procedural variables to minimise confounding.
      RESULTS: Severe SIRS developed in 6% of TAVR patients and 11% of SAVR patients
      (p=0.02). Six-month mortality tended to be higher in those with severe SIRS
      (15.5%) versus those without (7.4%) (p=0.07). After adjustment, severe SIRS was
      associated with higher 6-month mortality (IPW adjusted HR 2.77, 95% CI 2.04 to
      3.76, p<0.001). Moreover, severe SIRS was more strongly associated with increased
      mortality in diabetic (IPW adjusted HR 4.12, 95% CI 2.69 to 6.31, p<0.001) than
      non-diabetic patients (IPW adjusted HR 1.74, 95% CI 1.10 to 2.73, p=0.02)
      (interaction p=0.007). The adverse effect of severe SIRS on mortality was similar
      after TAVR and SAVR. CONCLUSIONS: Severe SIRS was associated with a higher
      mortality after SAVR or TAVR. It occurred more commonly after SAVR and had a
      greater effect on mortality in diabetic patients. These findings may have
      implications for treatment decisions in patients with AS, may help explain
      differences in outcomes between different AVR approaches and identify diabetic
      patients as a high-risk subgroup to target in clinical trials with therapies to
      attenuate SIRS.

PMID- 25605655
TI  - Positive selection drives neofunctionalization of the UbiA prenyltransferase gene
      family.
AB  - Gene duplication provides the key materials for new genes and novel functions.
      However, the mechanism underlying functional innovation remains unknown. In this
      study, we revealed the evolutionary pattern of the prenyltransferases of the UbiA
      gene family in 15 higher plants. Prenyltransferases of the UbiA gene family are
      involved in many important biological processes of both primary and secondary
      metabolism. Based on the phylogenetic relationships of the UbiA genes, seven
      subfamilies are classified. Confirming this classification, genes within each
      subfamily are characterized by similar exon numbers, exon lengths and patterns of
      motif combinations. Similar numbers of UbiA genes are found in different species
      within each subfamily except for Subfamily I, in which a Phaseoleae-specific
      expansion is detected in clade I-A. Homologous genes in clade I-A evolve rapidly,
      exchange sequences frequently and experience positive selection. Genes in clade I
      A function as flavonoid prenyltransferase synthesis secondary compounds, while
      other genes from Subfamily I encode homogentisate phytyltransferase, which plays
      a role in primary metabolism. Thus, our results suggest that the secondary
      metabolism genes acquire new functions from those of primary metabolism through
      gene duplication and neofunctionalization driven by positive selection. 

PMID- 25605656
TI  - Impact of intravascular ultrasound findings on long-term patency after self
      expanding nitinol stent implantation in the iliac artery lesion.
AB  - Although intravascular ultrasound (IVUS) predictors of stent patency for the
      coronary artery lesion have been established, little is known about IVUS
      predictors of stent patency for the aorto-iliac artery lesion. We analyzed 154
      lesions of 122 patients who underwent stent implantation for iliac artery
      lesions. Quantitative and qualitative IVUS analyses were performed for pre- and
      post-procedural IVUS imaging in all lesions. Target lesion revascularization
      (TLR) was defined as clinically driven revascularization with >50 % angiographic
      stenosis of the target lesion. The mean follow-up period was 39 +/- 16 months.
      TLRs were performed in 13 lesions (8.4 %). Post-procedural minimum stent area
      (MSA) was significantly smaller in the TLR group compared to the no-TLR group
      (16.0 +/- 5.8 vs. 25.6 +/- 8.5 mm(2), p < 0.001). Stent edge dissection was
      frequently observed in the TLR group compared to the no-TLR group (53.8 vs. 24.1
      %, p = 0.04). Multivariate analysis revealed that post-procedural MSA (OR = 0.76,
      p < 0.01) and stent edge dissection (OR = 10.4, p < 0.01) were independent IVUS
      predictors of TLR. Receiver-operating characteristic analysis identified post
      procedural MSA <17.8 mm(2) as the optimal cut-point for the prediction of TLR
      (AUC = 0.846). Post-procedural MSA and stent edge dissection could predict long
      term stent patency in the iliac artery lesion. Our results propose that adequate
      stent enlargement without edge dissection might be important to reduce TLR in the
      iliac artery lesion.

PMID- 25605658
TI  - A successful desensitization protocol for horse-derived antithymocyte globulin in
      severe aplastic anemia.
AB  - BACKGROUND: Horse antithymocyte globulin (h-ATG) (ATGAM((r)) ) is the first
      choice of treatment in very severe patients with aplastic anemia who do not have
      any HLA matched sibling donor. h-ATG is a heterologous serum that may cause
      anaphylaxis. Alternative treatment strategies must be planned in case of
      hypersensitivity. Desensitization must be considered in patients without an
      alternative treatment of choice. We aimed to present the h-ATG desensitization
      protocol and consider its effectiveness in patients with aplastic anemia who are
      hypersensitized with h-ATG and do not have an alternative treatment of choice.
      METHODS: Skin prick tests were performed with non-diluted solution in eight very
      severe patients with aplastic anemia who are followed up in Ege University
      Children's Hospital. Although skin prick test was found negative in these eight
      patients, different dilution h-ATG intradermal tests were performed and found
      positive in all patients. h-ATG desensitization program was started to these
      hypersensitized patients. RESULTS: Desensitization program was started to six
      male and two female very severe patients with aplastic anemia whose ages were
      between seven and 19 yr (median: 12.9 yr). All of the patients completed the
      desensitization program. While local reaction was seen in two patients, systemic
      reaction was seen in one patient and late reaction was seen in one patient during
      and after desensitization program. CONCLUSION: A successful desensitization
      program with h-ATG in children with aplastic anemia is presented. Even though
      there is not an exposure before to such high allergy potential heterologous
      serum, skin tests should be performed and desensitization must be started to
      patients who are hypersensitized to h-ATG. As the expected effectiveness of the
      treatment is so much, the desensitization protocol can be carried out safely and
      effectively with trained stuff although allergic reactions can be seen.

PMID- 25605657
TI  - Intra-cardiac echocardiography-guided stent implantation into stenosed superior
      vena cava in a patient with a history of contrast anaphylaxis.
AB  - A 37-year-old patient, who suffered from a repeated superior vena cava (SVC)
      syndrome, was scheduled for stent implantation into SVC, but suffered from
      contrast anaphylaxis. To monitor the procedure, we used intra-cardiac
      echocardiography and successfully implanted a stent. Placing an intra-cardiac
      echocardiographic catheter in the main pulmonary artery and facing towards the
      right, we could readily visualize stenosis in the SVC and inflation of the stent.
      Also looking up from right atrium, we noted proximal obstruction of the stent and
      confirmed the relief of obstruction after additional balloon dilation. This
      report leads to new application of intra-cardiac echocardiography for
      intervention of structural and vascular diseases other than inter-atrial septum. 

PMID- 25605659
TI  - Diagnostic differentiation of mild cognitive impairment due to Alzheimer's
      disease using a hippocampus-dependent test of spatial memory.
AB  - The hippocampus is one of the earliest brain regions affected in Alzheimer's
      disease (AD) and tests of hippocampal function have the potential to detect AD in
      its earliest stages. Given that the hippocampus is critically involved in
      allocentric spatial memory, this study applied a short test of spatial memory,
      the 4 Mountains Test (4MT), to determine whether test performance can
      differentiate mild cognitive impairment (MCI) patients with and without CSF
      biomarker evidence of underlying AD and whether the test can distinguish patients
      with MCI and mild AD dementia when applied in different cultural settings.
      Healthy controls (HC), patients with MCI, and mild AD dementia were recruited
      from study sites in UK and Italy. Study numbers were: HC (UK 20, Italy 10), MCI
      (UK 21, Italy 14), and AD (UK 11, Italy 9). Nineteen UK MCI patients were grouped
      into CSF biomarker-positive (MCI+, n = 10) and biomarker-negative (MCI-, n = 9)
      subgroups. Behavioral data were correlated with hippocampal volume and cortical
      thickness of the precuneus and posterior cingulate gyrus. Spatial memory was
      impaired in both UK and Italy MCI and AD patients. Test performance additionally
      differentiated between MCI+ and MCI- subgroups (P = 0.001). A 4MT score of <=8/15
      was associated with 100% sensitivity and 90% specificity for detection of early
      AD (MCI+ and mild AD dementia) in the UK population, and with 100% sensitivity
      and 50% specificity for detection of MCI and AD in the Italy sample. 4MT
      performance correlated with hippocampal volume in the UK population and cortical
      thickness of the precuneus in both study populations. In conclusion, performance
      on a hippocampus-sensitive test of spatial memory differentiates MCI due to AD
      with high diagnostic sensitivity and specificity. The observation that similar
      diagnostic sensitivity was obtained in two separate study populations, allied to
      the scalability and usability of the test in community memory clinics, supports
      future application of the 4MT in the diagnosis of pre-dementia due to AD.

PMID- 25605660
TI  - Metabolic syndrome from adolescence to early adulthood: effect of infancy-onset
      dietary counseling of low saturated fat: the Special Turku Coronary Risk Factor
      Intervention Project (STRIP).
AB  - BACKGROUND: Adolescent metabolic syndrome (MetS) predicts type 2 diabetes
      mellitus and subclinical atherosclerosis in adulthood. Our aim was to establish
      the relationship between an infancy-onset dietary intervention and risk of having
      MetS between 15 and 20 years of age. METHODS AND RESULTS: The Special Turku
      Coronary Risk Factor Intervention Project for Children (STRIP) study is a
      longitudinal, randomized atherosclerosis prevention trial in which repeated
      dietary counseling aiming at reducing intake of saturated fat took place from
      infancy to early adulthood. Participants who had complete data on the MetS
      components (waist circumference, blood pressure, triglycerides, glucose, high
      density lipoprotein cholesterol) at 15 (n=512), 16 (n=485), 17 (n=475), 18
      (n=459), 19 (n=439), and 20 (n=407) years of age were included in the study.
      Modified International Diabetes Foundation criteria with 80th/20th percentile
      cutoff points for the components were primarily applied in statistical analyses,
      and the results were replicated with the use of other pediatric MetS definitions.
      Between the ages of 15 and 20 years, the prevalence of MetS varied between 6.0%
      and 7.5% in participants in the intervention group and between 10% and 14% in the
      control group. The long-term relative risk of MetS was significantly lower in the
      intervention group (relative risk, 0.59; 95% confidence interval, 0.40-0.88;
      P=0.009). Of the individual MetS components, the intervention decreased risk of
      high blood pressure in both sexes (relative risk, 0.83; 95% confidence interval,
      0.70-0.99) and high triglycerides in male subjects (relative risk, 0.71; 95%
      confidence interval, 0.52-0.98). A statistically nonsignificant reduction was
      seen in the risk of high waist circumference in the intervention individuals
      (relative risk, 0.78; 95% confidence interval, 0.59-1.03). CONCLUSION: Repeated
      infancy-onset dietary intervention is effective in the prevention of MetS in
      adolescence. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00223600.

PMID- 25605661
TI  - Primordial prevention of cardiovascular disease.

PMID- 25605662
TI  - Effect of light conditions on anatomical and biochemical aspects of somatic and
      zygotic embryos of hybrid larch (Larix * marschlinsii).
AB  - BACKGROUND AND AIMS: In conifers, mature somatic embryos and zygotic embryos
      appear to resemble one another physiologically and morphologically. However,
      phenotypes of cloned conifer embryos can be strongly influenced by a number of in
      vitro factors and in some instances clonal variation can exceed that found in
      nature. This study examines whether zygotic embryos that develop within light
      opaque cones differ from somatic embryos developing in dark/light conditions in
      vitro. Embryogenesis in larch is well understood both in situ and in vitro and
      thus provides a suitable system for addressing this question. METHODS: Features
      of somatic and zygotic embryos of hybrid larch, Larix * marschlinsii, were
      quantified, including cotyledon numbers, protein concentration and phenol
      chemistry. Somatic embryos were placed either in light or darkness for the entire
      maturation period. Embryos at different developmental stages were embedded and
      sectioned for histological analysis. KEY RESULTS: Light, and to a lesser degree
      abscisic acid (ABA), influenced accumulation of protein and phenolic compounds in
      somatic and zygotic embryos. Dark-grown mature somatic embryos had more protein
      (91.77 +/- 11.26 ug protein mg(-1) f.wt) than either dark-grown zygotic embryos
      (62.40 +/- 5.58) or light-grown somatic embryos (58.15 +/- 10.02). Zygotic
      embryos never accumulated phenolic compounds at any stage, whereas somatic
      embryos stored phenolic compounds in the embryonal root caps and suspensors.
      Light induced the production of quercetrin (261.13 +/- 9.2 ug g(-1) d.wt) in
      somatic embryos. Mature zygotic embryos that were removed from seeds and placed
      on medium in light rapidly accumulated phenolics in the embryonal root cap and
      hypocotyl. Delaying germination with ABA delayed phenolic compound accumulation,
      restricting it to the embryonal root cap. CONCLUSIONS: In larch embryos, light
      has a negative effect on protein accumulation, but a positive effect on phenol
      accumulation. Light did not affect morphogenesis, e.g. cotyledon number. Somatic
      embryos produced different amounts of phenolics, such as quercetrin, depending on
      light conditions. The greatest difference was seen in the embryonal root cap in
      all embryo types and conditions.

PMID- 25605663
TI  - Enhancing catalytic activity by narrowing local energy gaps--X-ray studies of a
      manganese water oxidation catalyst.
AB  - Changes in the local electronic structure of the Mn 3d orbitals of a Mn catalyst
      derived from a dinuclear Mn(III) complex during the water oxidation cycle were
      investigated ex situ by X-ray absorption spectroscopy (XAS) and resonant
      inelastic X-ray scattering (RIXS) analyses. Detailed information about the Mn 3d
      orbitals, especially the local HOMO-LUMO gap on Mn sites revealed by RIXS
      analyses, indicated that the enhancement in catalytic activity (water oxidation)
      originated from the narrowing of the local HOMO-LUMO gap when electrical voltage
      and visible light illumination were applied simultaneously to the Mn catalytic
      system. 

PMID- 25605664
TI  - Cardiometabolic Profile Related to Body Adiposity Identifies Patients Eligible
      for Bariatric Surgery More Accurately than BMI.
AB  - BACKGROUND: Eligibility criteria for bariatric surgery (BS) are based on BMI and
      the presence of major comorbidities. Our aim was to analyze the usefulness of
      body adiposity determination in establishing the indication for BS. METHODS: In
      order to analyze the cardiometabolic risk according to eligibility criteria for
      BS, four groups were studied. Morbidly obese patients with BMI >= 40 kg/m(2) (n =
      360), and obese subjects with BMI >= 35 kg/m(2) and at least one comorbidity (n =
      431), represented two groups of patients meeting original NIH criteria for BS. A
      third group included two cohorts of patients with a high body fat (BF)% that do
      not meet the original NIH eligibility criteria for BS: patients with either a BMI
      <35 kg/m(2) or a BMI >= 35 kg/m(2) without comorbidities (n = 266, NEHF). Lean
      subjects by BMI were the reference group (n = 140). BMI, BF% and markers of
      insulin sensitivity, lipid profile, and cardiovascular risk were measured.
      RESULTS: Individuals from the NEHF group exhibited increased HbA1c (P < 0.05) and
      decreased insulin sensitivity evidenced by a significant reduction in QUICKI (P <
      0.001). Triglyceride concentrations were similarly increased (P < 0.05) in the
      three groups of obese patients. Uric acid concentrations were significantly
      elevated (P < 0.01) to a similar extent in the obese groups. Levels of the
      inflammatory marker CRP and hepatic enzymes were significantly increased in the
      three obese groups. CONCLUSION: The present study provides evidence for the
      existence of an adverse cardiometabolic profile in subjects currently considered
      to be outside traditional NIH guidelines but exhibiting a highly increased
      adiposity. It is concluded that body composition analysis yields valuable
      information to be incorporated into indication criteria for BS and that adiposity
      may be an independent indicator for BS.

PMID- 25605666
TI  - Spectrum of fungal and parasitic infections on fine needle aspiration cytology.
AB  - BACKGROUND: The incidence many fungal and parasitic lesions are on the rise over
      the decades. In this study, we have analyzed the spectrum of fungal and parasitic
      lesions diagnosed on fine needle aspiration cytology (FNAC) in a tertiary health
      care center. METHODS: This is a retrospective study conducted in the period three
      years and included all cases of fungal and parasitic lesions in the body
      (superficial and deep) identified on FNAC. RESULTS: There were total of 125 cases
      comprising of 59 parasitic cases and 66 fungal infections over this period. The
      various organisms were confirmed by special stains whenever required. In the
      parasitic group a cysticercosis (43), hydatid (8), filariasis (5), toxoplasmosis
      (1), leishmaniasis (1), and amoebiasis (1) were identified. The fungal infections
      included aspergillosis (36), mucormycosis (6), histoplasmosis (3), cryptococcus
      (4), and candidiasis (2). About a total of 15 cases were broadly classified as
      fungal infection only. CONCLUSIONS: FNAC is an easy, reliable, and minimally
      invasive method to diagnose and categorize the various fungal and parasitic
      lesions in the body for early and definitive treatment.

PMID- 25605667
TI  - A hybrid feature selection approach for the early diagnosis of Alzheimer's
      disease.
AB  - OBJECTIVE: Recently, significant advances have been made in the early diagnosis
      of Alzheimer's disease (AD) from electroencephalography (EEG). However, choosing
      suitable measures is a challenging task. Among other measures, frequency relative
      power (RP) and loss of complexity have been used with promising results. In the
      present study we investigate the early diagnosis of AD using synchrony measures
      and frequency RP on EEG signals, examining the changes found in different
      frequency ranges. APPROACH: We first explore the use of a single feature for
      computing the classification rate (CR), looking for the best frequency range.
      Then, we present a multiple feature classification system that outperforms all
      previous results using a feature selection strategy. These two approaches are
      tested in two different databases, one containing mild cognitive impairment (MCI)
      and healthy subjects (patients age: 71.9 +/- 10.2, healthy subjects age: 71.7 +/-
      8.3), and the other containing Mild AD and healthy subjects (patients age: 77.6
      +/- 10.0; healthy subjects age: 69.4 +/- 11.5). MAIN RESULTS: Using a single
      feature to compute CRs we achieve a performance of 78.33% for the MCI data set
      and of 97.56% for Mild AD. Results are clearly improved using the multiple
      feature classification, where a CR of 95% is found for the MCI data set using 11
      features, and 100% for the Mild AD data set using four features. SIGNIFICANCE:
      The new features selection method described in this work may be a reliable tool
      that could help to design a realistic system that does not require prior
      knowledge of a patient's status. With that aim, we explore the standardization of
      features for MCI and Mild AD data sets with promising results.

PMID- 25605665
TI  - Gamma-sarcoglycan is required for the response of archvillin to mechanical
      stimulation in skeletal muscle.
AB  - Loss of gamma-sarcoglycan (gamma-SG) induces muscle degeneration and signaling
      defects in response to mechanical load, and its absence is common to both
      Duchenne and limb girdle muscular dystrophies. Growing evidence suggests that
      aberrant signaling contributes to the disease pathology; however, the mechanisms
      of gamma-SG-mediated mechanical signaling are poorly understood. To uncover gamma
      SG signaling pathway components, we performed yeast two-hybrid screens and
      identified the muscle-specific protein archvillin as a gamma-SG and dystrophin
      interacting protein. Archvillin protein and message levels were significantly
      upregulated at the sarcolemma of murine gamma-SG-null (gsg(-/-)) muscle but
      delocalized in dystrophin-deficient mdx muscle. Similar elevation of archvillin
      protein was observed in human quadriceps muscle lacking gamma-SG. Reintroduction
      of gamma-SG in gsg(-/-) muscle by rAAV injection restored archvillin levels to
      that of control C57 muscle. In situ eccentric contraction of tibialis anterior
      (TA) muscles from C57 mice caused ERK1/2 phosphorylation, nuclear activation of P
      ERK1/2 and stimulus-dependent archvillin association with P-ERK1/2. In contrast,
      TA muscles from gsg(-/-) and mdx mice exhibited heightened P-ERK1/2 and increased
      nuclear P-ERK1/2 localization following eccentric contractions, but the
      archvillin-P-ERK1/2 association was completely ablated. These results position
      archvillin as a mechanically sensitive component of the dystrophin complex and
      demonstrate that signaling defects caused by loss of gamma-SG occur both at the
      sarcolemma and in the nucleus.

PMID- 25605668
TI  - Examination of mercaptobenzyl sulfonates as catalysts for native chemical
      ligation: application to the assembly of a glycosylated Glucagon-Like Peptide 1
      (GLP-1) analogue.
AB  - 3/4-Mercaptobenzyl sulfonates were investigated as aryl thiol catalysts for
      native chemical ligation (NCL). Whilst catalysing NCL processes at a similar rate
      to 4-mercaptophenyl acetic acid (MPAA), the increased polarity and solubility of
      3-mercaptobenzyl sulfonate in particular may favour its selection as NCL catalyst
      in many instances. 

PMID- 25605669
TI  - Excitation migration in fluctuating light-harvesting antenna systems.
AB  - Complex multi-exponential fluorescence decay kinetics observed in various
      photosynthetic systems like photosystem II (PSII) have often been explained by
      the reversible quenching mechanism of the charge separation taking place in the
      reaction center (RC) of PSII. However, this description does not account for the
      intrinsic dynamic disorder of the light-harvesting proteins as well as their
      fluctuating dislocations within the antenna, which also facilitate the repair of
      RCs, state transitions, and the process of non-photochemical quenching. Since
      dynamic fluctuations result in varying connectivity between pigment-protein
      complexes, they can also lead to non-exponential excitation decay kinetics. Based
      on this presumption, we have recently proposed a simple conceptual model
      describing excitation diffusion in a continuous medium and accounting for
      possible variations of the excitation transfer pathways. In the current work,
      this model is further developed and then applied to describe fluorescence
      kinetics originating from very diverse antenna systems, ranging from PSII of
      various sizes to LHCII aggregates and even the entire thylakoid membrane. In all
      cases, complex multi-exponential fluorescence kinetics are perfectly reproduced
      on the entire relevant time scale without assuming any radical pair equilibration
      at the side of the excitation quencher, but using just a few parameters
      reflecting the mean excitation energy transfer rate as well as the overall
      average organization of the photosynthetic antenna. 

PMID- 25605671
TI  - Reply: To PMID 25284802.

PMID- 25605670
TI  - Microfluidic model of ductal carcinoma in situ with 3D, organotypic structure.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast
      cancer that is thought to be a precursor to most invasive and metastatic breast
      cancers. Understanding the mechanisms regulating the invasive transition of DCIS
      is critical in order to better understand how some types of DCIS become invasive.
      While significant insights have been gained using traditional in vivo and in
      vitro models, existing models do not adequately recapitulate key structure and
      functions of human DCIS well. In addition, existing models are time-consuming and
      costly, limiting their use in routine screens. Here, we present a microscale DCIS
      model that recapitulates key structures and functions of human DCIS, while
      enhancing the throughput capability of the system to simultaneously screen
      numerous molecules and drugs. METHODS: Our microscale DCIS model is prepared in
      two steps. First, viscous finger patterning is used to generate mammary
      epithelial cell-lined lumens through extracellular matrix hydrogels. Next, DCIS
      cells are added to fill the mammary ducts to create a DCIS-like structure. For
      coculture experiments, human mammary fibroblasts (HMF) are added to the two side
      channels connected to the center channel containing DCIS. To validate the
      invasive transition of the DCIS model, the invasion of cancer cells and the loss
      of cell-cell junctions are then examined. A student t-test is conducted for
      statistical analysis. RESULTS: We demonstrate that our DCIS model faithfully
      recapitulates key structures and functions of human mammary DCIS and can be
      employed to study the mechanisms involved in the invasive progression of DCIS.
      First, the formation of cell-cell junctions and cell polarity in the normal
      mammary duct, and the structure of the DCIS model are characterized. Second,
      coculture with HMF is shown to induce the invasion of DCIS. Third, multiple
      endpoint analyses are demonstrated to validate the invasion. CONCLUSIONS: We have
      developed and characterized a novel in vitro model of normal and DCIS-inflicted
      mammary ducts with 3D lumen structures. These models will enable researchers to
      investigate the role of microenvironmental factors on the invasion of DCIS in
      more in vivo-like conditions.

PMID- 25605672
TI  - Editorial: "Interfering" with preeclampsia.

PMID- 25605673
TI  - Efficacy and safety of liraglutide therapy in 195 Indian patients with type 2
      diabetes in real world setting.
AB  - BACKGROUND: GLP-1 analogues has established role in the management of type 2
      diabetes mellitus (T2DM). Liraglutide, a human GLP-1 analogue is used as an
      adjunct to diet and exercise in adults with T2DM for improvement of glycemic
      control. OBJECTIVE: To assess the efficacy and safety of liraglutide in Indian
      patients with T2DM in real-world setting. METHODS: A prospective, open label,
      single arm, single centre, observational study of 24 weeks duration in a real
      world setting. Subjects with T2DM with impaired glucose control despite of
      antidiabetic therapy and clinically suitable for liraglutide therapy were
      enrolled and managed. All subjects received liraglutide therapy in addition to
      their existing anti-diabetic therapy. Starting dose of liraglutide (Victoza) was
      0.6 mg/day for 7 days followed by 1.2 mg/day for next 7 days and finally 1.8
      mg/day for 22 weeks. Subjects were evaluated at baseline and at 24 weeks. Adverse
      events (AE) noted during course of therapy were recorded. Student t test (two
      tailed, dependent) was performed for assessment of statistical significance.
      RESULTS: Total 195 subjects were studied over 24 weeks. Mean fasting plasma
      glucose (FPG) was decreased from 163.81 mg/dL to 111.6 (P<0.001); similarly HbA1c
      was reduced from 8.14% to 6.96% (P=0.006) at 24 weeks. At week 24, 49.23% and
      41.03% subjects treated with liraglutide reached an HbA1c<7.0% and <=6.5%,
      respectively. Mean weight was reduced from 86.41 kg to 82.37 kg (P<0.001).
      Additionally mean systolic and diastolic blood pressure was reduced from 129.31
      and 76.18 mm of Hg to 119.59 (P=0.90) and 70.88 (P<0.001) mm of Hg, respectively.
      Serum cholesterol was reduced from 166.68 mg/dL to 124.86 mg/dL (P<0.001). Twenty
      two (11.28%) subjects reported adverse events (AE), the most common AEs being
      vomiting, tiredness, loose motion and nausea. All AEs were mild to moderate in
      nature without any serious AE. CONCLUSION: In 195 Indian patients with T2DM
      receiving anti-diabetic drugs, addition of liraglutide resulted in significant
      improvement in glycemic parameters and was well tolerated. Clinically significant
      reduction in weight, blood pressure and serum cholesterol were also noted.

PMID- 25605674
TI  - Dairy product consumption and the metabolic syndrome.
AB  - AIMS: To briefly summarize findings from epidemiological studies on the
      relationship between dairy product consumption and the metabolic syndrome(MetS).
      MATERIALS AND METHODS: A search for relevant literature was undertaken on Web of
      Science, Google scholar, Pubmed (2000 to July 2013), to identify observational
      studies which examined the association between dairy intake and MetS (prevalence
      or incidence), and for any randomized controlled trials investigating the effect
      of dairy intake on MetS. RESULTS: Here we review the physiological effects and
      possible mechanisms involved of three main dairy constituents (calcium (Ca),
      protein, fat) on important components of the MetS. Effects of Ca may be related
      to intestinal binding to fatty acids or bile acids, or to changes in
      intracellular Ca metabolism by suppressing calciotropic hormones. Dietary
      proteins may increase satiety in both the short and longer term, which may result
      in a reduced energy intake. Dairy proteins are precursors of angiotensin-I
      converting enzyme-inhibitory peptides, which may lower blood pressure. To reduce
      the intake of saturated fatty acids (SFA), the consumption of low-fat instead of
      high-fat dairy products is recommended. CONCLUSION: More research is warranted to
      better understand the physiological effects and the mechanisms involved of dairy
      products in the prevention and treatment of the MetS.

PMID- 25605675
TI  - Oncologic outcomes of volume replacement technique after partial mastectomy for
      breast cancer: a single center analysis.
AB  - BACKGROUND AND OBJECTIVES: Volume replacement technique is a good option for
      Asian women with small to moderate-sized breasts undergoing partial mastectomy
      for breast cancer. We analyzed the oncologic outcomes of this procedure in a
      single center. METHODS: Seventy-two patients with breast cancer underwent partial
      mastectomy with volume replacement technique in this prospective study. Volume
      replacement techniques were tailored individually according to the volume of
      excised breast and tumor location. The mean duration of follow-up was 40.9
      months. We analyzed association between various clinicopathologic factors and
      locoregional recurrence, distant metastasis and assessed cosmetic outcomes.
      RESULTS: The incidences of locoregional recurrence and distant metastasis were
      2.8% and 5.6%, respectively. According to multivariate analysis, history of
      contralateral breast cancer (P < 0.001) and fat necrosis (P = 0.002)
      significantly associated with incidence of locoregional recurrence and pathologic
      tumor size (P = 0.037) and stage (P = 0.048) significantly influenced the
      incidence of distant metastasis. CONCLUSION: From an oncologic perspective,
      volume replacement procedures after partial mastectomy are an appropriate form of
      surgical management of breast cancer.

PMID- 25605676
TI  - Cost-effectiveness of preparticipation screening of athletes with ECG in Europe
      and Algeria.

PMID- 25605677
TI  - Blue toe syndrome, ischemic pain treated with digital block.

PMID- 25605678
TI  - Ultrasonography versus computed tomography for suspected nephrolithiasis.

PMID- 25605679
TI  - Chronic tissue response to untethered microelectrode implants in the rat brain
      and spinal cord.
AB  - OBJECTIVE: Microelectrodes implanted in the central nervous system (CNS) often
      fail in long term implants due to the immunological tissue response caused by
      tethering forces of the connecting wires. In addition to the tethering effect,
      there is a mechanical stress that occurs at the device-tissue interface simply
      because the microelectrode is a rigid body floating in soft tissue and it cannot
      reshape itself to comply with changes in the surrounding tissue. In the current
      study we evaluated the scar tissue formation to tetherless devices with two
      significantly different geometries in the rat brain and spinal cord in order to
      investigate the effects of device geometry. APPROACH: One of the implant
      geometries resembled the wireless, floating microstimulators that we are
      currently developing in our laboratory and the other was a (shank only) Michigan
      probe for comparison. Both electrodes were implanted into either the cervical
      spinal cord or the motor cortices, one on each side. MAIN RESULTS: The most
      pronounced astroglial and microglial reactions occurred within 20 MUm from the
      device and decreased sharply at larger distances. Both cell types displayed the
      morphology of non-activated cells past the 100 MUm perimeter. Even though the
      aspect ratios of the implants were different, the astroglial and microglial
      responses to both microelectrode types were very mild in the brain, stronger and
      yet limited in the spinal cord. SIGNIFICANCE: These observations confirm previous
      reports and further suggest that tethering may be responsible for most of the
      tissue response in chronic implants and that the electrode size has a smaller
      contribution with floating electrodes. The electrode size may be playing
      primarily an amplifying role to the tethering forces in the brain whereas the
      size itself may induce chronic response in the spinal cord where the movement of
      surrounding tissues is more significant.

PMID- 25605680
TI  - Cytologic features of ovarian granulosa cell tumors in pleural and ascitic
      fluids.
AB  - Adult granulosa cell tumor (AGCT) is an uncommon neoplasm of the ovary with
      potential for aggressive behavior and late recurrence. The most important
      prognostic factor for AGCT is tumor stage. Thus, cytological assessment of
      pleural or ascitic fluids is crucial for initial staging and subsequent patient
      management. We report herein two cases of ovarian AGCT presenting with exfoliated
      tumor cells in pleural and ascitic fluid. The first case involved a 61-year-old
      woman who presented with stage Ic (a) AGCT. Seven years after initial diagnosis,
      pleural effusion and pleural dissemination were identified. The second case
      involved a 50-year-old woman who presented with stage IV AGCT with massive
      ascites and right pleural effusion. Fluid cytology from both cases showed
      cohesive or loose clusters of small uniform neoplastic cells with round-to-oval
      nuclei, coffee-bean-shaped nuclear grooves, small nucleoli, and scant cytoplasm.
      Call-Exner bodies were also observed in these cytologic specimens. In the
      differential diagnosis of small monomorphic tumor cells in pleural effusion or
      ascites, coffee-bean-shaped nuclear grooves and cell clusters forming Call-Exner
      bodies are diagnostic clues of AGCT.

PMID- 25605681
TI  - Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors
      to cardiovascular disease and all-cause mortality in 90000 individuals from the
      general population.
AB  - BACKGROUND: Increased nonfasting remnant cholesterol, like increased LDL
      cholesterol, is causally associated with increased risk for ischemic heart
      disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting
      remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial
      infarction (MI), and all-cause mortality. METHODS: We compared stepwise
      increasing concentrations of nonfasting remnant and LDL cholesterol for
      association with risk of IHD, MI, and all-cause mortality in approximately 90 000
      individuals from the Danish general population. During up to 22 years of complete
      follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died.
      RESULTS: Compared with participants with nonfasting remnant cholesterol <0.5
      mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1-1.5) for
      remnant cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2.4 (1.9-2.9) for
      remnant cholesterol of >=1.5 mmol/L (58 mg/dL) (P for trend <0.001). Compared
      with participants with LDL cholesterol <3.0 mmol/L (115.8 mg/dL), hazard ratios
      for IHD ranged from 1.3 (1.1-1.5) for LDL cholesterol of 3-3.99 mmol/L (115.8-154
      mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol of >=5 mmol/L (193 mg/dL) (P <
      0.001). Corresponding hazard ratios for MI ranged from 1.8 (1.4-2.3) to 3.4 (2.5
      4.8) for remnant cholesterol (P < 0.001), and from 1.7 (1.4-2.2) to 4.7 (3.5-6.3)
      for LDL cholesterol (P < 0.001). Nonfasting remnant cholesterol concentrations
      were associated stepwise with all-cause mortality ranging from hazard ratio 1.0
      (0.9-1.1) to 1.6 (1.4-1.9) (P < 0.001), whereas LDL cholesterol concentrations
      were associated with decreased all-cause mortality risk in a U-shaped pattern,
      with hazard ratios from 0.8 (0.7-0.8) to 0.9 (0.8-1.0) (P = 0.002). After mutual
      adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best
      predicted all-cause mortality. CONCLUSIONS: Both lipoproteins were associated
      equally with risk of IHD and MI; however, only nonfasting remnant cholesterol
      concentrations were associated stepwise with increased all-cause mortality risk.

PMID- 25605682
TI  - Neuromedin U: a multifunctional neuropeptide with pleiotropic roles.
AB  - BACKGROUND: Neuromedin U (NmU) belongs to the neuromedin family, comprising a
      series of neuropeptides involved in the gut-brain axis and including neuromedins
      B and C (bombesin-like), K (neurokinin B), L (neurokinin A or neurotensin), N, S,
      and U. CONTENT: Although initially isolated from porcine spinal cord on the basis
      of their ability to induce uterine smooth muscle contraction, these peptides have
      now been found to be expressed in several different tissues and have been
      ascribed numerous functions, from appetite regulation and energy balance control
      to muscle contraction and tumor progression. NmU has been detected in several
      species to date, particularly in mammals (pig, rat, rabbit, dog, guinea pig,
      human), but also in amphibian, avian, and fish species. The NmU sequence is
      highly conserved across different species, indicating that this peptide is
      ancient and plays an important biological role. Here, we summarize the main
      structural and functional characteristics of NmU and describe its many roles,
      highlighting the jack-of-all-trades nature of this neuropeptide. SUMMARY: NmU
      involvement in key processes has outlined the possibility that this neuropeptide
      could be a novel target for the treatment of obesity and cancer, among other
      disorders. Although the potential for NmU as a therapeutic target is obvious, the
      multiple functions of this molecule should be taken into account when designing
      an approach to targeting NmU and/or its receptors.

PMID- 25605683
TI  - Brain tumor mutations detected in cerebral spinal fluid.
AB  - BACKGROUND: Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain
      tumor patients is challenging, presumably owing to the blood-brain barrier.
      Cerebral spinal fluid (CSF) may serve as an alternative "liquid biopsy" of brain
      tumors by enabling measurement of circulating DNA within CSF to characterize
      tumor-specific mutations. Many aspects about the characteristics and
      detectability of tumor mutations in CSF remain undetermined. METHODS: We used
      digital PCR and targeted amplicon sequencing to quantify tumor mutations in the
      cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also,
      we applied cancer panel sequencing to globally characterize the somatic mutation
      profile from the CSF of 1 patient with suspected leptomeningeal disease. RESULTS:
      We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain
      tumors. The concentration of the tumor mutant alleles varied widely between
      patients, from <5 to nearly 3000 copies/mL CSF. We identified 7 somatic mutations
      from the CSF of a patient with leptomeningeal disease by use of cancer panel
      sequencing, and the result was concordant with genetic testing on the primary
      tumor biopsy. CONCLUSIONS: Tumor mutations were detectable in cfDNA from the CSF
      of patients with different primary and metastatic brain tumors. We designed 2
      strategies to characterize tumor mutations in CSF for potential clinical
      diagnosis: the targeted detection of known driver mutations to monitor brain
      metastasis and the global characterization of genomic aberrations to direct
      personalized cancer care.

PMID- 25605684
TI  - Multiple reaction monitoring with multistage fragmentation (MRM3) detection
      enhances selectivity for LC-MS/MS analysis of plasma free metanephrines.
AB  - BACKGROUND: LC-MS/MS with multiple reaction monitoring (MRM) is a powerful tool
      for quantifying target analytes in complex matrices. However, the technique lacks
      selectivity when plasma free metanephrines are measured. We propose the use of
      multistage fragmentation (MRM(3)) to improve the analytical selectivity of plasma
      free metanephrine measurement. METHODS: Metanephrines were extracted from plasma
      with weak cation exchange solid-phase extraction before separation by hydrophilic
      interaction liquid chromatography. We quantified normetanephrine and metanephrine
      by either MRM or MRM(3) transitions m/z 166->134->79 and m/z 180->149->121,
      respectively. RESULTS: Over a 6-month period, approximately 1% (n = 21) of
      patient samples showed uncharacterized coeluting substances that interfered with
      the routine assay, resulting in an inability to report results. Quantification
      with MRM(3) removed these interferences and enabled measurement of the target
      compounds. For patient samples unaffected by interferences, Deming regression
      analysis demonstrated a correlation between MRM(3) and MRM methods of y = 1.00x -
      0.00 nmol/L for normetanephrine and y = 0.99x + 0.03 nmol/L for metanephrine.
      Between the MRM(3) method and the median of all LC-MS/MS laboratories enrolled in
      a quality assurance program, the correlations were y = 0.97x + 0.03 nmol/L for
      normetanephrine and y = 1.03x - 0.04 nmol/L for metanephrine. Imprecision for the
      MRM(3) method was 6.2%-7.0% for normetanephrine and 6.1%-9.9% for metanephrine (n
      = 10). The lower limits of quantification for the MRM(3) method were 0.20 nmol/L
      for normetanephrine and 0.16 nmol/L for metanephrine. CONCLUSIONS: The use of
      MRM(3) technology improves the analytical selectivity of plasma free metanephrine
      quantification by LC-MS/MS while demonstrating sufficient analytical sensitivity
      and imprecision.

PMID- 25605685
TI  - Superior electrocatalytic activity from nanodendritic structure consisting of a
      PtFe bimetallic core and Pt shell.
AB  - A novel PtFe@Pt core-shell nanostructure with a PtFe bimetallic core and a
      nanodendrite Pt shell was fabricated through a facile aqueous reduction process.
      Without any capping agent and/or surfactant, a clean Pt surface can be obtained.
      The novel nanostrutured crystals show superior electrocatalytic performance
      towards methanol oxidation due to the enlarged Pt surface area and the modified
      electronic structure of Pt. 

PMID- 25605686
TI  - Practical aspects of treatment with target specific anticoagulants: initiation,
      payment and current market, transitions, and venous thromboembolism treatment.
AB  - Target specific anticoagulants (TSOACs) have recently been introduced to the US
      market for multiple indications including venous thromboembolism (VTE) prevention
      in total hip and knee replacement surgeries, VTE treatment and reduction in the
      risk of stroke in patients with non-valvular atrial fibrillation (NVAF).
      Currently, three TSOACs are available including rivaroxaban, apixaban, and
      dabigatran with edoxaban currently under Food and Drug Administration review for
      VTE treatment and stroke prevention in NVAF. The introduction of these agents has
      created a paradigm shift in anticoagulation by considerably simplifying treatment
      and anticoagulant initiation for patients by giving clinicians the opportunity to
      use a rapid onset, rapid offset, oral agent. The availability of these rapid
      onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism
      and deep vein thrombosis which can greatly reduce healthcare costs by avoiding
      inpatient hospitalizations and treatment for the disease. Additionally with this
      practice, the complications of an inpatient hospitalization may also be avoided
      such as nosocomial infections. Single-agent approaches with TSOACs represent a
      paradigm shift in the treatment of VTE versus the complicated overlap of a
      parenteral agent with warfarin. Transitions between anticoagulants, including
      TSOACs, are a high-risk period for the patient, and clinicians must carefully
      consider patient characteristics such as renal function as well as the agents
      that are being transitioned. TSOAC use appears to be growing slowly with improved
      payment coverage throughout the US. 

PMID- 25605687
TI  - Alcohol use disorders are associated with venous thromboembolism.
AB  - Moderate alcohol consumption has been suggested to protect against venous
      thromboembolism (VTE). However, it is not known how alcohol abuse and its
      associated somatic complications affect the risk of VTE. The present study
      determined the risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) of
      the lower extremities in patients with alcohol use disorders (AUDs) in Sweden.
      All inpatients with AUDs in 2002-2010 without a previous VTE event (72,024
      patients) were matched to five controls without AUD and followed until the end of
      follow-up (December 31, 2010), death, emigration or a VTE event. Cox regression
      was used to determine adjusted hazard ratios (HRs) for VTE. AUD patients were
      further divided into those without alcohol-related somatic complications (AUD-)
      and those with alcohol-related somatic complications (AUD+, i.e., encephalopathy,
      epilepsy, polyneuropathy, myopathy, cardiomyopathy, gastritis, liver disease,
      acute pancreatitis, and chronic pancreatitis). The adjusted HR for VTE was
      significantly increased for both AUD- (HR 1.70, 95 % CI 1.55-1.87) and AUD+ (HR
      1.73, 95 % CI 1.37-2.19) patients. The risk of DVT was increased in both AUD+ and
      AUD- patients (HR 1.62, 95 % CI 1.45-1.83 and HR 1.99, 95 % CI 1.53-2.59,
      respectively). However, the risk of PE was only significantly increased in AUD-
      patients (HR 1.87, 95 % 1.59-1.20) and not in AUD+ patients (HR 1.16, 95 % 0.70
      1.91). In conclusion, the present study shows that AUD increases the risk of VTE,
      even in the absence of alcohol-related somatic complications. Our findings
      suggest that severe alcohol abuse increases the risk of VTE. 

PMID- 25605688
TI  - Randomized, controlled trial of percutaneous cryoablation versus radiofrequency
      ablation in hepatocellular carcinoma.

PMID- 25605689
TI  - Mott insulator-to-metal transition in yttrium-doped CaIrO3.
AB  - We report on the study of insulator-to-metal transition in post-perovskite
      compound CaIrO3. It is discovered that a gradual chemical substitution of calcium
      by yttrium leads to the onset of strong metallic behavior in this compound. This
      observation is in stark contrast to BaIrO3, which preserves its Mott insulating
      behavior despite excess of the charge carriers due to yttrium doping. Magnetic
      measurements reveal that both compounds tend to exhibit magnetic character
      irrespective of the chemical substitution of Ca or Ba. We analyze these unusual
      observations in light of recent researches that suggest that CaIrO3 does not
      necessarily possess j = 1/2 ground state due to structural distortion. The
      insulator-to-metal transition in CaIrO3 will spur new researches to explore more
      exotic ground state, including superconductivity, in post-perovskite Mott
      insulators.

PMID- 25605690
TI  - Randomized controlled trial of supplemental augmentative and alternative
      communication versus voice rest alone after phonomicrosurgery.
AB  - OBJECTIVE: This randomized trial investigated voice rest and supplemental text-to
      speech communication versus voice rest alone on visual analog scale measures of
      communication effectiveness and magnitude of voice use. STUDY DESIGN: Randomized
      clinical trial. SETTING: Multicenter outpatient voice clinics. SUBJECTS: Thirty
      seven patients undergoing phonomicrosurgery. METHODS: Patients undergoing
      phonomicrosurgery were randomized to voice rest and supplemental text-to-speech
      communication or voice rest alone. The primary outcome measure was the impact of
      voice rest on ability to communicate effectively over a 7-day period. Pre- and
      postoperative magnitude of voice use was also measured as an observational
      outcome. RESULTS: Patients randomized to voice rest and supplemental text-to
      speech communication reported higher median communication effectiveness on each
      postoperative day compared to those randomized to voice rest alone, with
      significantly higher median communication effectiveness on postoperative days 3
      (P=.03) and 5 (P=.01). Magnitude of voice use did not differ on any preoperative
      (P>.05) or postoperative day (P>.05), nor did patients significantly decrease
      voice use as the surgery date approached (P>.05). However, there was a
      significant reduction in median voice use pre- to postoperatively across patients
      (P<.001) with median voice use ranging from 0 to 3 throughout the postoperative
      week. CONCLUSION: Supplemental text-to-speech communication increased patient
      perceived communication effectiveness on postoperative days 3 and 5 over voice
      rest alone. With the prevalence of smartphones and the widespread use of text
      messaging, supplemental text-to-speech communication may provide an accessible
      and cost-effective communication option for patients on vocal restrictions.

PMID- 25605691
TI  - 228 cases of cochlear implant receiver-stimulator placement in a tight
      subperiosteal pocket without fixation.
AB  - OBJECTIVES: (1) To investigate the outcomes of cochlear implant receiver
      stimulator (RS) placement using a tight subperiosteal pocket technique without
      device fixation and (2) to compare the efficiency of this approach with the
      traditional bony well and trough technique. STUDY DESIGN: Case series with
      planned chart review. SETTING: Single tertiary academic referral center. SUBJECTS
      AND METHODS: All cochlear implant surgeries utilizing a tight subperiosteal
      pocket without additional fixation or use of a bone well were identified
      retrospectively. Revision cases were only included if the tight subperiosteal
      pocket technique was used during the initial surgery. Patients with less than 6
      months of postoperative follow-up were excluded. Primary outcome measures
      included RS migration, flap complications, device failure, and percentage
      reduction in operative time. RESULTS: Two hundred twenty-eight cases (average age
      45.3 years) met inclusion criterion and were analyzed. At a mean follow-up of
      18.1 months, no patient experienced RS migration. One patient experienced a
      postoperative hematoma that was managed with observation. One patient developed a
      surgical site infection that resolved following exploration and intravenous
      antibiotics. The subperiosteal pocket technique resulted in an 18.9% reduction in
      total operative time compared to a more conventional RS placement method (P <
      .01). CONCLUSIONS: The tight subperiosteal pocket without fixation is a safe,
      durable, and time-saving technique for RS placement during cochlear implantation.
      Notably, device migration and flap complications are very uncommon.

PMID- 25605692
TI  - How much does the type of tympanostomy tube matter? A utility-based Markov
      decision analysis.
AB  - OBJECTIVES: To use a utility-based Markov decision analysis model to compare
      outcomes of short-term grommet tympanostomy tubes (TTs), intermediate-type tubes,
      and permanent T-Tubes and to use a detailed sensitivity analysis to determine the
      most important factors influencing outcomes with one type of TT versus another.
      STUDY DESIGN: Markov decision analysis. SETTING: Hypothetical cohort. SUBJECTS
      AND METHODS: A Markov cohort decision analysis model was created using computer
      software (TreeAge Software, Inc, Williamstown, Massachusetts) comparing the 3
      types of TT. Published data were used to determine key baseline model parameters.
      The model featured potential complications including eardrum perforation, early
      TT extrusion/blockage, and the need for possible repeat TT placement after
      extrusion. Outcomes were quantified using a 0.95 (1 procedure, full recovery) to
      0.6 (failed myringoplasty) utility scale. Utility values were discounted over
      time to incorporate real-life inconvenience. RESULTS: The intermediate TT
      accumulated superior total utility in 2-, 4-, and 6-year models (2.48, 3.96, and
      5.27 total utility) compared with grommets (2.32, 3.82, 5.18) and T-Tubes (2.42,
      3.86, 5.18). Examining a hypothetically otherwise healthy 3000-child cohort, T
      Tubes resulted in an increased overall persistent perforation rate (7.9% vs 0.2%,
      P < .001, chi(2)). Sensitivity analysis indicated that the rate of repeat TT
      placement, the utility assigned to having a functional tube in place, and the
      inconvenience utility discount factor over time were the driving factors of the
      model. CONCLUSION: The intermediate TT may produce optimal outcomes as it
      combines a balance of a lower perforation rate than T-Tubes and a longer period
      of ventilation than grommet tubes.

PMID- 25605693
TI  - Attenuation of streptomycin ototoxicity by tetramethylpyrazine in guinea pig
      cochlea.
AB  - OBJECTIVE: Tetramethylpyrazine has been suggested to have a therapeutic effect on
      impaired hearing that is induced by aminoglycoside antibiotics. However, its
      effectiveness on streptomycin ototoxicity and its cellular mechanisms are
      relatively unknown. Here we investigate the protective effect of
      tetramethylpyrazine on streptomycin-induced ototoxicity in guinea pig cochlea.
      STUDY DESIGN: Prospective randomized laboratory study. SETTING: Hearing Research
      Laboratory of China Medical University. SUBJECTS AND METHODS: Adult guinea pigs
      were randomized to 4 groups. Hearing sensitivity of guinea pigs was tested by
      auditory brainstem response measurements before streptomycin exposure and again
      10 days later. The cochlear tissues were prepared for electron microscopy and
      immunohistochemical staining of heat shock protein 70 (HSP70). The effect of
      tetramethylpyrazine on streptomycin-induced activation of caspase-3 was evaluated
      by Western blotting. RESULTS: Co-therapy with tetramethylpyrazine reduced a
      profound streptomycin-induced auditory threshold shift compared with streptomycin
      treatment alone (P = .0002 or P = .00008). Tetramethylpyrazine also attenuated
      the structural disruption in streptomycin-treated outer hair cells and marginal
      cells of vascular stria by transmission electronic microscopy and scanning
      electronic microscopy, respectively. Moreover, tetramethylpyrazine decreased the
      streptomycin-stimulated expressions of HSP70 and caspase-3. The correlation
      analysis demonstrated that HSP70 expression had a positive correlation with
      auditory brainstem response thresholds (|R| = 0.6-0.9, P = .0073 or P = .0169).
      CONCLUSIONS: Our data suggest that the protective effect of tetramethylpyrazine
      on hearing function is associated with the reduction of stress response and
      inhibition of apoptosis. Tetramethylpyrazine may have therapeutic potential for
      patients with ototoxicity diseases.

PMID- 25605694
TI  - Balloon eustachian tuboplasty: a systematic review.
AB  - OBJECTIVE: A systematic review and meta-analysis of the evidence on balloon
      Eustachian tuboplasty (BET) as a treatment modality for Eustachian tube
      dysfunction (ETD). We followed the PRISMA guideline and registered with PROSPERO
      No. CRD42014009461. DATA SOURCES: We searched 12 databases including PubMed and
      Embase from January 1, 2010, to April 7, 2014, for studies of BET. ENDPOINTS:
      change in symptoms, middle ear pathology, eardrum status, Eustachian tube
      function tests, hearing, adverse events, complications, and health-related
      quality of life. REVIEW METHODS: Study quality was assessed using the modified
      Delphi technique quality appraisal tool for case series studies. Risk of bias was
      assessed using the Cochrane Collaboration's tool for assessing risk of bias.
      RESULTS: Nine case series studies with 443 patients (642 tubes) were included.
      Population size n=4 (7 tubes) to n=210 (320 tubes). All studies were of poor
      quality and featured a high risk of bias. We found reduction of patient symptoms
      in ETD questionnaire (P<.001), postoperative normalization of the tympanic
      membrane, conversion of type B or type C into type A tympanograms, reduced
      mucosal inflammation, increased number of positive Valsalva test and Swallowing
      tests, improvement in Eustachian tube score, reduction in Sino-Nasal Outcome Test
      (SNOT)-22 score (P=.001), and increased quality of life (P=.001). No serious
      adverse events were found. CONCLUSION: The evidence of BET is poor and biased. No
      firm conclusions can be made to identify patients who will benefit from the
      procedure or to accurately predict surgical results. Randomized controlled trials
      or case-control trials are needed.

PMID- 25605695
TI  - Current status of clinical trials in head and neck cancer 2014.
AB  - INTRODUCTION: The last few years have seen significant increase in the number of
      available clinical trials in head and neck cancer. It has been difficult to stay
      abreast of these efforts because multiple cooperative groups and institutions are
      engaged in their recruitment. This review presents the state of the art of
      available clinical trials organized around major research themes. DATA SOURCES:
      Published literature, published cooperative group monographs, expert review.
      REVIEW METHODS: Initial themes in head and neck cancer clinical trial development
      were first identified along with examples. Opinions from an international panel
      of multidisciplinary experts were then solicited. RESULTS/DISCUSSION: Current
      major themes of head and neck clinical trials centered on 5 major themes: (1)
      recognition of human papillomavirus oropharynx cancer and optimal treatment
      strategies, (2) defining the role of transoral surgery in head and neck cancer
      treatment, (3) improving postoperative adjuvant treatment, (4) investigation of
      rare malignancies, and (5) the importance of biomarker-driven, innovative, and
      targeted therapy investigation. CONCLUSIONS: A number of exciting clinical trials
      are currently in development or accrual with the potential for tremendous impact
      and improvement of the treatment of head and neck cancer. IMPLICATIONS FOR
      PRACTICE: Awareness by practicing otolaryngologists and trainees of these current
      themes will be essential for study accrual, success, and improvement in the care
      of head and neck cancer.

PMID- 25605696
TI  - National trends in retropharyngeal abscess among adult inpatients with
      peritonsillar abscess.
AB  - OBJECTIVES: To describe national trends in retropharyngeal abscess (RPA)
      complicating peritonsillar abscess (PTA) and to determine factors associated with
      RPA in patients with PTA. STUDY DESIGN: Cross-sectional analysis. SETTING:
      Nationwide Inpatient Sample, 2003-2010. SUBJECTS AND METHODS: PTA patients >=18
      years old, with or without RPA, were extracted according to ICD-9-CM codes. The
      cohort was analyzed with descriptive statistics and multivariate regression
      modeling to identify factors associated with RPA. RESULTS: Of the 91,647 (95% CI:
      86,433-95,449) patients identified with PTA, 885 (1.0%) also had a concurrently
      coded RPA. The annual rate of concomitant RPA increased from 0.5% (95% CI: 0.3%
      0.8%) to 1.4% (95% CI: 1.0%-2.0%) between 2003 and 2010 (P < .001). PTA patients
      with RPA more frequently underwent tonsillectomy (23.5% vs 11.1%), endotracheal
      intubation (7.1% vs 1.5%), and mechanical ventilation (13.2% vs 2.0%) than those
      without RPA (all P < .001). PTA patients with RPA were significantly older (41 vs
      34 years old), had a longer hospital stay (6.4 vs 2.5 days), and had more
      procedures (2.5 vs 0.9) when compared to patients without RPA (all P < .001).
      Upon multivariate regression analysis, factors associated with RPA included the
      age groups of 40 to 64 years (odds ratio, 2.256; P < .001) and 65 and older (odds
      ratio, 2.086; P = .045). Median total charges for PTA inpatients with concomitant
      RPA were approximately $8700 greater (P < .001) when compared to patients with
      PTA alone. CONCLUSIONS: The incidence of RPA among adult inpatients with PTA is
      increasing, and patients with RPA have higher in-hospital resource utilization.
      Further studies may help validate factors predictive of RPA to enable prevention
      or earlier identification.

PMID- 25605697
TI  - Esophageal visualization as an adjunct to the videofluoroscopic study of
      swallowing.
AB  - OBJECTIVE: Complaints of dysphagia for solids lead to speech-language pathology
      (SLP) referral. Yet many of these patients are later diagnosed with esophageal
      rather than oropharyngeal dysphagia. Fluoroscopic screening involving the
      oropharynx alone fails to identify these patients. The aim of this study was to
      investigate the prevalence of esophageal abnormalities in an SLP-led
      videofluoroscopic study of swallowing (VFSS) clinic. STUDY DESIGN: Prospective,
      observational study. SETTING: Radiology suite, public hospital. SUBJECTS AND
      METHODS: In total, 111 consecutive mixed-etiology patients referred to the clinic
      by otorhinolaryngology (ORL) (59) or by a speech-language pathologist (52) were
      recruited. A VFSS was performed according to protocol, and at completion,
      esophageal visualization (in anterior-posterior plane) was performed by
      administration of a large liquid barium bolus and a barium capsule. All VFSS
      recordings were analyzed using objective digital measures of timing and
      displacement. RESULTS: Sixty-eight percent of patients had an abnormal esophageal
      transit. One-third of those referred presented exclusively with esophageal
      abnormalities, while one-third had both oropharyngeal and esophageal
      abnormalities. Oral abnormalities, reduced pharyngoesophageal segment maximum
      opening (PESmax), and increasing age were significantly associated with
      esophageal abnormalities. CONCLUSION: Fluoroscopic evaluation of the pharynx
      alone, without esophageal review, risks incomplete diagnosis of patients with
      esophageal disorders. Using esophageal visualization allows timely referral for
      further investigation by appropriate medical specialties, avoiding incomplete
      management of patients with dysphagia.

PMID- 25605698
TI  - Comparison of local and intravenous dexamethasone for postoperative pain and
      recovery after tonsillectomy.
AB  - OBJECTIVE: To compare local infiltration of dexamethasone to intravenous
      injection for postoperative pain and recovery after tonsillectomy. STUDY DESIGN:
      Prospective, randomized study. SETTING: Second Affiliated Hospital of Harbin
      Medical University. SUBJECTS AND METHODS: Children (n=240, American Society of
      Anesthesiologists [ASA] classes I-II, aged 5-10 y) scheduled for tonsillectomy
      were randomly and equally assigned to 3 groups: DEX-IV, for intravenous injection
      of dexamethasone (0.5 mg/kg, maximum dose 24 mg); DEX-INF, given the same amount
      of dexamethasone by local infiltration to the upper middle and lower poles of the
      tonsils; and a control group not given dexamethasone. Postoperative pain was
      scored at intervals from 30 minutes to 24 hours. The time to first administration
      of analgesic and average consumption of analgesic, times to first oral water and
      solid food intake, and incidence rates of nausea and vomiting were evaluated.
      RESULTS: From postoperative 1 to 16 hours, the DEX-INF group had significantly
      lower pain scores than did the DEX-IV group, and the time to first analgesic and
      average consumption of analgesic were also significantly lower. The times to
      first oral water and food intake in the DEX-INF group were significantly shorter
      than in the DEX-IV group. The incidence of nausea and vomiting in the DEX-INF
      group was higher than that of the DEX-IV group. CONCLUSION: Local infiltration of
      dexamethasone was more effective than systemic administration to decrease pain
      and time to food intake, but the antiemetic effect was less. CLINICAL TRIALS
      REGISTRATION NUMBER: ChiCTR-TRC-13003535.

PMID- 25605699
TI  - Can we save the kidneys by protecting the heart?

PMID- 25605701
TI  - Trends in perinatal health after assisted reproduction: a Nordic study from the
      CoNARTaS group.
AB  - STUDY QUESTIONS: Has the perinatal outcome of children conceived after assisted
      reproductive technology (ART) improved over time? SUMMARY ANSWER: The perinatal
      outcomes in children born after ART have improved over the last 20 years, mainly
      due to the reduction of multiple births. WHAT IS KNOWN AND WHAT THIS PAPER ADDS:
      A Swedish study has shown a reduction in unwanted outcomes over time in children
      conceived after ART. Our analyses based on data from more than 92 000 ART
      children born in four Nordic countries confirm these findings. STUDY DESIGN:
      Nordic population-based matched cohort study with ART outcome and health data
      from Denmark, Finland, Norway and Sweden. PARTICIPANTS, SETTING AND METHODS: We
      analysed the perinatal outcome of 62 379 ART singletons and 29 758 ART twins,
      born from 1988 to 2007 in four Nordic countries. The ART singletons were compared
      with a control group of 362 215 spontaneously conceived singletons. Twins
      conceived after ART were compared with all spontaneously conceived twins (n = 122
      763) born in the Nordic countries during the study period. The rates of several
      adverse perinatal outcomes were stratified into the time periods: 1988-1992; 1993
      1997; 1998-2002 and 2003-2007 and presented according to multiplicity. MAIN
      RESULTS AND ROLE OF CHANCE: For singletons conceived after ART, a remarkable
      decline in the risk of being born preterm and very preterm was observed. The
      proportion of ART singletons born with a low and very low birthweight also
      decreased. Finally, the stillbirth and infant death rates have declined among
      both ART singletons and twins. Throughout the 20 year period, fewer ART twins
      were stillborn or died during the first year of life compared with spontaneously
      conceived twins, presumably due to the lower proportion of monozygotic twins
      among the ART twins. LIMITATIONS, REASONS FOR CAUTION: We were not able to adjust
      for some potential confounders such as BMI, smoking, length or cause of
      infertility. The Nordic ART populations have changed over time, and in recent
      years, both less as well as severely reproductive ill couples are being treated.
      This may have affected the observed trends. WIDER IMPLICATIONS OF THE FINDINGS:
      It is assuring that data from four countries confirm an overall improvement over
      time in the perinatal outcomes of children conceived after ART. Furthermore, data
      show the beneficial effect of single embryo transfer, not only in regard to
      lowering the rate of multiples but also concerning the health of singletons.
      STUDY FUNDING/COMPETING INTERESTS: The European Society for Human Reproduction
      and Embryology (ESHRE), the University of Copenhagen and the Danish Agency for
      Science, Technology and Innovation has supported the project. The CoNARTaS group
      has received travel and meeting funding from the Nordic Federation of Obstetrics
      and Gynecology (NFOG). None of the authors has any competing interests to
      declare.

PMID- 25605700
TI  - NT-proBNP and troponin T and risk of rapid kidney function decline and incident
      CKD in elderly adults.
AB  - BACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic
      peptide and high-sensitivity troponin T are associated with poor cardiovascular
      outcomes. Whether elevations in these cardiac biomarkers are associated with
      decline in kidney function was evaluated. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were
      measured at baseline in 3752 participants free of heart failure in the
      Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease
      Epidemiology Collaboration equation using serum cystatin C. Rapid decline in
      kidney function was defined as decline in serum cystatin C eGFR>=30%, and
      incident CKD was defined as the onset of serum cystatin C eGFR<60 among those
      without CKD at baseline (n=2786). Cox regression models were used to examine the
      associations of each biomarker with kidney function decline adjusting for
      demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk
      factors. RESULTS: In total, 503 participants had rapid decline in serum cystatin
      C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants
      developed incident CKD over a mean follow-up time of 6.41 (1.74) years.
      Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide
      (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk
      of incident CKD compared with participants in the lowest quartile (adjusted
      hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence
      interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence
      interval, 1.08 to 1.76). Participants in the highest category of troponin T
      (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants
      in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval,
      1.35 to 2.40). The association of troponin T with incident CKD was not
      statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to
      1.50). CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and
      troponin T are associated with rapid decline of kidney function and incident CKD.
      Additional studies are needed to evaluate the mechanisms that may explain this
      association.

PMID- 25605702
TI  - Reply: Endometrial injury and reproductive outcomes: there's more to this story
      than meets the horse's blind eye.

PMID- 25605703
TI  - Endometrial injury and reproductive outcomes: there's more to this story than
      meets the horse's blind eye.

PMID- 25605704
TI  - Activation of Toll-like receptor 3 reduces actin polymerization and adhesion
      molecule expression in endometrial cells, a potential mechanism for viral-induced
      implantation failure.
AB  - STUDY QUESTION: Does activation of endometrial Toll-like receptor 3 (TLR 3)
      affect cell receptivity to trophoblast adhesion? SUMMARY ANSWER: TLR 3 activation
      in vitro reduces the attachment of trophoblast cells to endometrial cells by
      altering the cell cytoskeleton and reducing the expression of adhesion molecules
      in human endometrial cells. WHAT IS KNOWN ALREADY: It is well documented that the
      presence of an infection at the time of implantation can lead to implantation
      failure. The female reproductive tract recognizes invading micro-organisms
      through the innate pathogen recognition receptors such as the TLRs. STUDY DESIGN,
      SIZE, DURATION: Poly I:C was used as a TLR 3-specific ligand and endometrial
      cells were either treated or not with Poly I:C (treated versus control) in vitro.
      The experiments were performed in three replicates on three separate days.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: An in vitro assay was developed using
      RL95-2 (a human endometrial cell line) and JAr (a human trophoblast cell line)
      cells. Initially, the percentage of attached JAr spheroids to RL95-2 was measured
      in response to TLR 3 activation. Next, actin polymerization in RL95-2 cells was
      assessed in response to TLR 2/6, 3 and 5 activation. Phalloidin was used to
      assess the mean fluorescence intensity of F-actin by flow cytometry or confocal
      microscopy. Secondly, the influence of TLR 2/6, 3 and 5 activation on the
      expression of cluster of differentiation 98 (CD98) and beta3 integrin was
      determined. To further understand through which pathways the TLR 3-induced
      alterations occur, inhibitors were applied for Toll/interleukin-1 receptor domain
      containing adaptor inducing interferon-beta (TRIF), myeloid differentiation
      primary response 88 (MYD88), mitogen-activated protein kinases (MAPK) and nuclear
      factor pathways. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that
      stimulation of TLR 3 in endometrial cells with different concentrations of Poly
      I:C led to a reduction in the percentage of trophoblasts attached to the
      endometrial cells in a dose-dependent manner (P < 0.05). This decrease was
      consistent in the Poly I:C treated group regardless of the co-incubation time (P
      < 0.05). In addition, our results demonstrated that actin polymerization and CD98
      expression significantly decreased only in response to TLR 3 activation (P <
      0.05). Activation of endometrial cells with TLR 2/6, 3 and 5 significantly
      reduced beta3 integrin expression (P < 0.05). These alterations were shown to
      work via MYD88-MAPK pathways (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This
      study has been performed in vitro. Future in vivo studies will be required in
      order to confirm our data. WIDER IMPLICATIONS OF THE FINDINGS: This is a novel
      discovery which extends our current knowledge concerning diagnosis and treatment
      of viral-induced infertility cases. STUDY FUNDING/COMPETING INTERESTS: This
      research was supported by the COST Action FA1201 (GEMINI) by granting a Short
      Term Scientific Mission and the Instituto de Salud Carlos III by granting Grant
      PI11/01645. The authors have no conflict of interest to declare.

PMID- 25605706
TI  - Prevalence of Underprescription or Overprescription of Energy Needs in Critically
      Ill Mechanically Ventilated Adults as Determined by Indirect Calorimetry: A
      Systematic Literature Review.
AB  - BACKGROUND: Underfeeding and overfeeding has been associated with adverse patient
      outcomes. Resting energy expenditure can be measured using indirect calorimetry.
      In its absence, predictive equations are used. A systematic literature review was
      conducted to determine the prevalence of underprescription and overprescription
      of energy needs in adult mechanically ventilated critically ill patients by
      comparing predictive equations to indirect calorimetry measurements. METHODS:
      Ovid MEDLINE, CINAHL Plus, Scopus, and EMBASE databases were searched in May 2013
      to identify studies that used both predictive equations and indirect calorimetry
      to determine energy expenditure. Reference lists of included publications were
      also searched. The number of predictive equations that underestimated or
      overestimated energy expenditure by +/-10% when compared to indirect calorimetry
      measurements were noted at both an individual and group level. RESULTS: In total,
      2349 publications were retrieved, with 18 studies included. Of the 160 variations
      of 13 predictive equations reviewed at a group level, 38% underestimated and 12%
      overestimated energy expenditure by more than 10%. The remaining 50% of equations
      estimated energy expenditure to within +/-10 of indirect calorimetry
      measurements. On an individual patient level, predictive equations underestimated
      and overestimated energy expenditure in 13-90% and 0-88% of patients,
      respectively. Differences of up to 43% below and 66% above indirect calorimetry
      values were observed. CONCLUSIONS: Large discrepancies exist between predictive
      equation estimates and indirect calorimetry measurements in individuals and
      groups. Further research is needed to determine the influence of indirect
      calorimetry and predictive equation limitations in contributing to these observed
      differences.

PMID- 25605705
TI  - Molecular basis of non-syndromic hypospadias: systematic mutation screening and
      genome-wide copy-number analysis of 62 patients.
AB  - STUDY QUESTION: What percentage of cases with non-syndromic hypospadias can be
      ascribed to mutations in known causative/candidate/susceptibility genes or
      submicroscopic copy-number variations (CNVs) in the genome? SUMMARY ANSWER:
      Monogenic and digenic mutations in known causative genes and cryptic CNVs account
      for >10% of cases with non-syndromic hypospadias. While known susceptibility
      polymorphisms appear to play a minor role in the development of this condition,
      further studies are required to validate this observation. WHAT IS KNOWN ALREADY:
      Fifteen causative, three candidate, and 14 susceptible genes, and a few
      submicroscopic CNVs have been implicated in non-syndromic hypospadias. STUDY
      DESIGN, SIZE, DURATION: Systematic mutation screening and genome-wide copy-number
      analysis of 62 patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study
      group consisted of 57 Japanese and five Vietnamese patients with non-syndromic
      hypospadias. Systematic mutation screening was performed for 25 known
      causative/candidate/susceptibility genes using a next-generation sequencer.
      Functional consequences of nucleotide alterations were assessed by in silico
      assays. The frequencies of polymorphisms in the patient group were compared with
      those in the male general population. CNVs were analyzed by array-based
      comparative genomic hybridization and characterized by fluorescence in situ
      hybridization. MAIN RESULTS AND THE ROLE OF CHANCE: Seven of 62 patients with
      anterior or posterior hypospadias carried putative pathogenic mutations, such as
      hemizygous mutations in AR, a heterozygous mutation in BNC2, and homozygous
      mutations in SRD5A2 and HSD3B2. Two of the seven patients had mutations in
      multiple genes. We did not find any rare polymorphisms that were abundant
      specifically in the patient group. One patient carried mosaic dicentric Y
      chromosome. LIMITATIONS, REASONS FOR CAUTION: The patient group consisted solely
      of Japanese and Vietnamese individuals and clinical and hormonal information of
      the patients remained rather fragmentary. In addition, mutation analysis focused
      on protein-altering substitutions. WIDER IMPLICATIONS OF THE FINDINGS: Our data
      provide evidence that pathogenic mutations can underlie both mild and severe
      hypospadias and that HSD3B2 mutations cause non-syndromic hypospadias as a sole
      clinical manifestation. Most importantly, this is the first report documenting
      possible oligogenicity of non-syndromic hypospadias. STUDY FUNDING/COMPETING
      INTERESTS: This study was funded by the Grant-in-Aid from the Ministry of
      Education, Culture, Sports, Science and Technology; by the Grant-in-Aid from the
      Japan Society for the Promotion of Science; by the Grants from the Ministry of
      Health, Labour and Welfare, from the National Center for Child Health and
      Development and from the Takeda Foundation. The authors have no competing
      interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 25605707
TI  - Psychological language on Twitter predicts county-level heart disease mortality.
AB  - Hostility and chronic stress are known risk factors for heart disease, but they
      are costly to assess on a large scale. We used language expressed on Twitter to
      characterize community-level psychological correlates of age-adjusted mortality
      from atherosclerotic heart disease (AHD). Language patterns reflecting negative
      social relationships, disengagement, and negative emotions-especially anger
      emerged as risk factors; positive emotions and psychological engagement emerged
      as protective factors. Most correlations remained significant after controlling
      for income and education. A cross-sectional regression model based only on
      Twitter language predicted AHD mortality significantly better than did a model
      that combined 10 common demographic, socioeconomic, and health risk factors,
      including smoking, diabetes, hypertension, and obesity. Capturing community
      psychological characteristics through social media is feasible, and these
      characteristics are strong markers of cardiovascular mortality at the community
      level.

PMID- 25605708
TI  - Sexual conflict arising from extrapair matings in birds.
AB  - The discovery that extrapair copulation (EPC) and extrapair paternity (EPP) are
      common in birds led to a paradigm shift in our understanding of the evolution of
      mating systems. The prevalence of extrapair matings in pair-bonded species sets
      the stage for sexual conflict, and a recent focus has been to consider how this
      conflict can shape variation in extrapair mating rates. Here, we invert the
      causal arrow and consider the consequences of extrapair matings for sexual
      conflict. Extrapair matings shift sexual conflict from a simple two-player (male
      vs. female) game to a game with three or more players, the nature of which we
      illustrate with simple diagrams that highlight the net costs and benefits of
      extrapair matings to each player. This approach helps identify the sorts of
      traits that might be under selection because of sexual conflict. Whether EPP is
      driven primarily by the extrapair male or the within-pair female profoundly
      influences which players are in conflict, but the overall pattern of conflict
      varies little among different mating systems. Different aspects of conflict are
      manifest at different stages of the breeding cycle and can be profitably
      considered as distinct episodes of selection caused by conflict. This perspective
      is illuminating both because conflict between specific players can change across
      episodes and because the traits that evolve to mediate conflict likely differ
      between episodes. Although EPP clearly leads to sexual conflict, we suggest that
      the link between sexual conflict and multiple paternity might be usefully
      understood by examining how deviations from lifetime sexual monogamy influence
      sexual conflict. 

PMID- 25605709
TI  - Astrocyte calcium signaling: from observations to functions and the challenges
      therein.
AB  - We provide an overview of recent progress on the study of astrocyte intracellular
      Ca(2+) signaling. We consider the methods that have been used to monitor
      astrocyte Ca(2+) signals, the various types of Ca(2+) signals that have been
      discovered (waves, microdomains, and intrinsic fluctuations), the approaches used
      to broadly trigger and block Ca(2+) signals, and, where possible, the proposed
      and demonstrated physiological roles for astrocyte Ca(2+) signals within neuronal
      microcircuits. Although important progress has been made, we suggest that further
      detailed work is needed to explore the biophysics and molecular mechanisms of
      Ca(2+) signaling within entire astrocytes, including their fine distal
      extensions, such as processes that interact spatially with neurons and blood
      vessels. Improved methods are also needed to mimic and block molecularly defined
      types of Ca(2+) signals within genetically specified populations of astrocytes.
      Moreover, it will be essential to study astrocyte Ca(2+) activity in vivo to
      distinguish between pharmacological and physiological activity, and to study
      Ca(2+) activity in situ to rigorously explore mechanisms. Once methods to
      reliably measure, mimic, and block specific astrocyte Ca(2+) signals with high
      temporal and spatial precision are available, researchers will be able to
      carefully explore the correlative and causative roles that Ca(2+) signals may
      play in the functions of astrocytes, blood vessels, neurons, and microcircuits in
      the healthy and diseased brain. 

PMID- 25605710
TI  - Meiosis: an overview of key differences from mitosis.
AB  - Meiosis is the specialized cell division that generates gametes. In contrast to
      mitosis, molecular mechanisms and regulation of meiosis are much less understood.
      Meiosis shares mechanisms and regulation with mitosis in many aspects, but also
      has critical differences from mitosis. This review highlights these differences
      between meiosis and mitosis. Recent studies using various model systems revealed
      differences in a surprisingly wide range of aspects, including cell-cycle
      regulation, recombination, postrecombination events, spindle assembly, chromosome
      spindle interaction, and chromosome segregation. Although a great degree of
      diversity can be found among organisms, meiosis-specific processes, and
      regulation are generally conserved.

PMID- 25605711
TI  - Keratinocyte growth factor administration attenuates murine pulmonary
      mycobacterium tuberculosis infection through granulocyte-macrophage colony
      stimulating factor (GM-CSF)-dependent macrophage activation and phagolysosome
      fusion.
AB  - Augmentation of innate immune defenses is an appealing adjunctive strategy for
      treatment of pulmonary Mycobacterium tuberculosis infections, especially those
      caused by drug-resistant strains. The effect of intranasal administration of
      keratinocyte growth factor (KGF), an epithelial mitogen and differentiation
      factor, on M. tuberculosis infection in mice was tested in prophylaxis,
      treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis
      resulted in inoculum size-dependent weight loss and mortality. A single dose of
      KGF given 1 day prior to infection with 10(5) M. tuberculosis bacilli prevented
      weight loss and enhanced pulmonary mycobacterial clearance (compared with saline
      pretreated mice) for up to 28 days. Similar effects were seen when KGF was
      delivered intranasally every third day for 15 days, but weight loss and bacillary
      growth resumed when KGF was withdrawn. For mice with a well established M.
      tuberculosis infection, KGF given every 3 days beginning on day 15
      postinoculation was associated with reversal of weight loss and an increase in M.
      tuberculosis clearance. In in vitro co-culture experiments, M. tuberculosis
      infected macrophages exposed to conditioned medium from KGF-treated alveolar type
      II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent killing through
      mechanisms that included promotion of phagolysosome fusion and induction of
      nitric oxide. Alveolar macrophages from KGF-treated mice also exhibited enhanced
      GM-CSF-dependent phagolysosomal fusion. These results provide evidence that
      administration of KGF promotes M. tuberculosis clearance through GM-CSF-dependent
      mechanisms and enhances host defense against M. tuberculosis infection. 

PMID- 25605712
TI  - Disruption of a conserved CAP-D3 threonine alters condensin loading on mitotic
      chromosomes leading to chromosome hypercondensation.
AB  - The condensin complex plays a key role in organizing mitotic chromosomes. In
      vertebrates, there are two condensin complexes that have independent and
      cooperative roles in folding mitotic chromosomes. In this study, we dissect the
      role of a putative Cdk1 site on the condensin II subunit CAP-D3 in chicken DT40
      cells. This conserved site has been shown to activate condensin II during
      prophase in human cells, and facilitate further phosphorylation by polo-like
      kinase I. We examined the functional significance of this phosphorylation mark by
      mutating the orthologous site of CAP-D3 (CAP-D3(T1403A)) in chicken DT40 cells.
      We show that this mutation is a gain of function mutant in chicken cells; it
      disrupts prophase, results in a dramatic shortening of the mitotic chromosome
      axis, and leads to abnormal INCENP localization. Our results imply
      phosphorylation of CAP-D3 acts to limit condensin II binding onto mitotic
      chromosomes. We present the first in vivo example that alters the ratio of
      condensin I:II on mitotic chromosomes. Our results demonstrate this ratio is a
      critical determinant in shaping mitotic chromosomes. 

PMID- 25605713
TI  - Fat/vessel-derived secretory protein (Favine)/CCDC3 is involved in lipid
      accumulation.
AB  - We previously identified a novel gene encoding Favine/CCDC3 (NCBI protein entry
      NP_083080), a possible secretory factor, the mRNA of which is highly expressed in
      adipose tissue and the aorta. The Favine mRNA levels are increased in the course
      of differentiation of rat primary adipocytes and are more elevated in the adipose
      tissue of genetically obese and diet-induced obese mice than in lean mice.
      However, its biological function has not yet been elucidated until now. Here, we
      tested the hypothesis that Favine is involved in lipid metabolism in adipocytes.
      We found that overexpression of Favine promoted 3T3-L1 adipocyte differentiation.
      To further investigate the function of Favine in vivo, we generated Favine knock
      out (KO) mice. Favine KO mice exhibited a lean phenotype as they aged. The
      weights of white adipose tissue and liver were less, and adipocyte size was
      smaller in Favine KO mice compared with wild-type littermates (WT). Expression
      levels of lipogenic genes, such as fatty-acid synthase (FAS), acetyl-CoA
      carboxylase alpha (ACC1), and diacylglycerol O-acyltransferase-2 (Dgat2), were
      decreased in adipose tissue of Favine KO mice. In 1-year-old mice, Favine
      deficiency decreased the number of inflammatory cells in white adipose tissue and
      diminished hepatic steatosis. In vitro, deficiency of Favine attenuated
      differentiation of primary adipocytes. Taken together, these data demonstrate
      that Favine has adipogenic and lipogenic effects on adipocytes. 

PMID- 25605714
TI  - Recognition of bacterial signal peptides by mammalian formyl peptide receptors: a
      new mechanism for sensing pathogens.
AB  - Formyl peptide receptors (FPRs) are G-protein-coupled receptors that function as
      chemoattractant receptors in innate immune responses. Here we perform systematic
      structure-function analyses of FPRs from six mammalian species using structurally
      diverse FPR peptide agonists and identify a common set of conserved agonist
      properties with typical features of pathogen-associated molecular patterns.
      Guided by these results, we discover that bacterial signal peptides, normally
      used to translocate proteins across cytoplasmic membranes, are a vast family of
      natural FPR agonists. N-terminally formylated signal peptide fragments with
      variable sequence and length activate human and mouse FPR1 and FPR2 at low
      nanomolar concentrations, thus establishing FPR1 and FPR2 as sensitive and broad
      signal peptide receptors. The vomeronasal receptor mFpr-rs1 and its sequence
      orthologue hFPR3 also react to signal peptides but are much more narrowly tuned
      in signal peptide recognition. Furthermore, all signal peptides examined here
      function as potent activators of the innate immune system. They elicit robust,
      FPR-dependent calcium mobilization in human and mouse leukocytes and trigger a
      range of classical innate defense mechanisms, such as the production of reactive
      oxygen species, metalloprotease release, and chemotaxis. Thus, bacterial signal
      peptides constitute a novel class of immune activators that are likely to
      contribute to mammalian immune defense against bacteria. This evolutionarily
      conserved detection mechanism combines structural promiscuity with high
      specificity and enables discrimination between bacterial and eukaryotic signal
      sequences. With at least 175,542 predicted sequences, bacterial signal peptides
      represent the largest and structurally most heterogeneous class of G-protein
      coupled receptor agonists currently known for the innate immune system. 

PMID- 25605715
TI  - ADP-ribosylation factor 6 (ARF6) bidirectionally regulates dendritic spine
      formation depending on neuronal maturation and activity.
AB  - Recent studies have reported conflicting results regarding the role of ARF6 in
      dendritic spine development, but no clear answer for the controversy has been
      suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or
      negatively regulates dendritic spine formation depending on neuronal maturation
      and activity. ARF6 activation increased the spine formation in developing
      neurons, whereas it decreased spine density in mature neurons. Genome-wide
      microarray analysis revealed that ARF6 activation in each stage leads to opposite
      patterns of expression of a subset of genes that are involved in neuronal
      morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the
      coincident factor in both stages, but the antagonistic RhoA pathway becomes
      involved in the mature stage. Furthermore, blocking neuronal activity in
      developing neurons using tetrodotoxin or enhancing the activity in mature neurons
      using picrotoxin or chemical long term potentiation reversed the effect of ARF6
      on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine
      structures may play a role in structural plasticity of mature neurons. 

PMID- 25605716
TI  - Thematic minireview series: cell biology of G protein signaling.
AB  - This thematic series is on the topic of cell signaling from a cell biology
      perspective, with a particular focus on G proteins. G protein-coupled receptors
      (GPCRs, also known as seven-transmembrane receptors) are typically found at the
      cell surface. Upon agonist binding, these receptors will activate a GTP-binding G
      protein at the cytoplasmic face of the plasma membrane. Additionally, there is
      growing evidence that G proteins can also be activated by non-receptor binding
      partners, and they can signal from non-plasma membrane compartments. The
      production of second messengers at multiple, spatially distinct locations
      represents a type of signal encoding that has been largely neglected. The first
      minireview in the series describes biosensors that are being used to monitor G
      protein signaling events in live cells. The second describes the implementation
      of antibody-based biosensors to dissect endosome signaling by G proteins and
      their receptors. The third describes the function of a non-receptor, cytoplasmic
      activator of G protein signaling, called GIV (Girdin). Collectively, the advances
      described in these articles provide a deeper understanding and emerging
      opportunities for new pharmacology. 

PMID- 25605717
TI  - Systematic mapping of WNT-FZD protein interactions reveals functional selectivity
      by distinct WNT-FZD pairs.
AB  - The seven-transmembrane-spanning receptors of the FZD1-10 class are bound and
      activated by the WNT family of lipoglycoproteins, thereby inducing a complex
      network of signaling pathways. However, the specificity of the interaction
      between mammalian WNT and FZD proteins and the subsequent signaling cascade
      downstream of the different WNT-FZD pairs have not been systematically addressed
      to date. In this study, we determined the binding affinities of various WNTs for
      different members of the FZD family by using bio-layer interferometry and
      characterized their functional selectivity in a cell system. Using purified WNTs,
      we show that different FZD cysteine-rich domains prefer to bind to distinct WNTs
      with fast on-rates and slow off-rates. In a 32D cell-based system engineered to
      overexpress FZD2, FZD4, or FZD5, we found that WNT-3A (but not WNT-4, -5A, or 
      9B) activated the WNT-beta-catenin pathway through FZD2/4/5 as measured by
      phosphorylation of LRP6 and beta-catenin stabilization. Surprisingly, different
      WNT-FZD pairs showed differential effects on phosphorylation of DVL2 and DVL3,
      revealing a previously unappreciated DVL isoform selectivity by different WNT-FZD
      pairs in 32D cells. In summary, we present extensive mapping of WNT-FZD cysteine
      rich domain interactions complemented by analysis of WNT-FZD pair functionality
      in a unique cell system expressing individual FZD isoforms. Differential WNT-FZD
      binding and selective functional readouts suggest that endogenous WNT ligands
      evolved with an intrinsic natural bias toward different downstream signaling
      pathways, a phenomenon that could be of great importance in the design of FZD
      targeting drugs. 

PMID- 25605718
TI  - The endosomal sorting complex required for transport pathway mediates chemokine
      receptor CXCR4-promoted lysosomal degradation of the mammalian target of
      rapamycin antagonist DEPTOR.
AB  - G protein-coupled receptor (GPCR) signaling mediates many cellular functions,
      including cell survival, proliferation, and cell motility. Many of these
      processes are mediated by GPCR-promoted activation of Akt signaling by mammalian
      target of rapamycin complex 2 (mTORC2) and the phosphatidylinositol 3-kinase
      (PI3K)/phosphoinositide-dependent kinase 1 (PDK1) pathway. However, the molecular
      mechanisms by which GPCRs govern Akt activation by these kinases remain poorly
      understood. Here, we show that the endosomal sorting complex required for
      transport (ESCRT) pathway mediates Akt signaling promoted by the chemokine
      receptor CXCR4. Pharmacological inhibition of heterotrimeric G protein Galphai or
      PI3K signaling and siRNA targeting ESCRTs blocks CXCR4-promoted degradation of
      DEPTOR, an endogenous antagonist of mTORC2 activity. Depletion of ESCRTs by siRNA
      leads to increased levels of DEPTOR and attenuated CXCR4-promoted Akt activation
      and signaling, consistent with decreased mTORC2 activity. In addition, ESCRTs
      likely have a broad role in Akt signaling because ESCRT depletion also attenuates
      receptor tyrosine kinase-promoted Akt activation and signaling. Our data reveal a
      novel role for the ESCRT pathway in promoting intracellular signaling, which may
      begin to identify the signal transduction pathways that are important in the
      physiological roles of ESCRTs and Akt. 

PMID- 25605719
TI  - A single herpesvirus protein can mediate vesicle formation in the nuclear
      envelope.
AB  - Herpesviruses assemble capsids in the nucleus and egress by unconventional
      vesicle-mediated trafficking through the nuclear envelope. Capsids bud at the
      inner nuclear membrane into the nuclear envelope lumen. The resulting
      intralumenal vesicles fuse with the outer nuclear membrane, delivering the
      capsids to the cytoplasm. Two viral proteins are required for vesicle formation,
      the tail-anchored pUL34 and its soluble interactor, pUL31. Whether cellular
      proteins are involved is unclear. Using giant unilamellar vesicles, we show that
      pUL31 and pUL34 are sufficient for membrane budding and scission. pUL34 function
      can be bypassed by membrane tethering of pUL31, demonstrating that pUL34 is
      required for pUL31 membrane recruitment but not for membrane remodeling. pUL31
      can inwardly deform membranes by oligomerizing on their inner surface to form
      buds that constrict to vesicles. Therefore, a single viral protein can mediate
      all events necessary for membrane budding and abscission. 

PMID- 25605720
TI  - The cytoplasmic domain of a disintegrin and metalloproteinase 10 (ADAM10)
      regulates its constitutive activity but is dispensable for stimulated ADAM10
      dependent shedding.
AB  - The membrane-anchored metalloproteinase a disintegrin and metalloprotease 10
      (ADAM10) is required for shedding of membrane proteins such as EGF, betacellulin,
      the amyloid precursor protein, and CD23 from cells. ADAM10 is constitutively
      active and can be rapidly and post-translationally enhanced by several stimuli,
      yet little is known about the underlying mechanism. Here, we use ADAM10-deficient
      cells transfected with wild type or mutant ADAM10 to address the role of its
      cytoplasmic and transmembrane domain in regulating ADAM10-dependent protein
      ectodomain shedding. We report that the cytoplasmic domain of ADAM10 negatively
      regulates its constitutive activity through an ER retention motif but is
      dispensable for its stimulated activity. However, chimeras with the extracellular
      domain of ADAM10 and the transmembrane domain of ADAM17 with or without the
      cytoplasmic domain of ADAM17 show reduced stimulated shedding of the ADAM10
      substrate betacellulin, whereas the ionomycin-stimulated shedding of the ADAM17
      substrates CD62-L and TGFalpha is not affected. Moreover, we show that influx of
      extracellular calcium activates ADAM10 but is not essential for its activation by
      APMA and BzATP. Finally, the rapid stimulation of ADAM10 is not significantly
      affected by incubation with proprotein convertase inhibitors for up to 8 h,
      arguing against a major role of increased prodomain removal in the rapid
      stimulation of ADAM10. Thus, the cytoplasmic domain of ADAM10 negatively
      influences constitutive shedding through an ER retention motif, whereas the
      cytoplasmic domain and prodomain processing are not required for the rapid
      activation of ADAM10-dependent shedding events. 

PMID- 25605721
TI  - Modulation of plasma membrane Ca2+-ATPase by neutral phospholipids: effect of the
      micelle-vesicle transition and the bilayer thickness.
AB  - The effects of lipids on membrane proteins are likely to be complex and unique
      for each membrane protein. Here we studied different
      detergent/phosphatidylcholine reconstitution media and tested their effects on
      plasma membrane Ca(2+) pump (PMCA). We found that Ca(2+)-ATPase activity shows a
      biphasic behavior with respect to the detergent/phosphatidylcholine ratio.
      Moreover, the maximal Ca(2+)-ATPase activity largely depends on the length and
      the unsaturation degree of the hydrocarbon chain. Using static light scattering
      and fluorescence correlation spectroscopy, we monitored the changes in
      hydrodynamic radius of detergent/phosphatidylcholine particles during the micelle
      vesicle transition. We found that, when PMCA is reconstituted in mixed micelles,
      neutral phospholipids increase the enzyme turnover. The biophysical changes
      associated with the transition from mixed micelles to bicelles increase the time
      of residence of the phosphorylated intermediate (EP), decreasing the enzyme
      turnover. Molecular dynamics simulations analysis of the interactions between
      PMCA and the phospholipid bilayer in which it is embedded show that in the 1,2
      dioleoyl-sn-glycero-3-phosphocholine bilayer, charged residues of the protein are
      trapped in the hydrophobic core. Conversely, in the 1,2-dimyristoyl-sn-glycero-3
      phosphocholine bilayer, the overall hydrophobic-hydrophilic requirements of the
      protein surface are fulfilled the best, reducing the thermodynamic cost of
      exposing charged residues to the hydrophobic core. The apparent mismatch produced
      by a 1,2-dioleoyl-sn-glycero-3-phosphocholine thicker bilayer could be a
      structural foundation to explain its functional effect on PMCA. 

PMID- 25605722
TI  - Third transmembrane domain of the adrenocorticotropic receptor is critical for
      ligand selectivity and potency.
AB  - The ACTH receptor, known as the melanocortin-2 receptor (MC2R), plays an
      important role in regulating and maintaining adrenocortical function. MC2R is a
      subtype of the melanocortin receptor (MCR) family and has unique characteristics
      among MCRs. Endogenous ACTH is the only endogenous agonist for MC2R, whereas the
      melanocortin peptides alpha-, beta-, and gamma-melanocyte-stimulating hormone and
      ACTH are full agonists for all other MCRs. In this study, we examined the
      molecular basis of MC2R responsible for ligand selectivity using ACTH analogs and
      MC2R mutagenesis. Our results indicate that substitution of Phe(7) with D-Phe or
      D-naphthylalanine (D-Nal(2')) in ACTH(1-24) caused a significant decrease in
      ligand binding affinity and potency. Substitution of Phe(7) with D-Nal(2') in
      ACTH(1-24) did not switch the ligand from agonist to antagonist at MC2R, which
      was observed in MC3R and MC4R. Substitution of Phe(7) with D-Phe(7) in ACTH(1-17)
      resulted in the loss of ligand binding and activity. Molecular analysis of MC2R
      indicated that only mutation of the third transmembrane domain of MC2R resulted
      in a decrease in D-Phe ACTH binding affinity and potency. Our results suggest
      that Phe(7) in ACTH plays an important role in ligand selectivity and that the
      third transmembrane domain of MC2R is crucial for ACTH selectivity and potency.

PMID- 25605723
TI  - Single-cell analysis of G-protein signal transduction.
AB  - The growing use of fluorescent biosensors to directly probe the spatiotemporal
      dynamics of biochemical processes in living cells has revolutionized the study of
      intracellular signaling. In this review, we summarize recent developments in the
      use of biosensors to illuminate the molecular details of G-protein-coupled
      receptor (GPCR) signaling pathways, which have long served as the model for our
      understanding of signal transduction, while also offering our perspectives on the
      future of this exciting field. Specifically, we highlight several ways in which
      biosensor-based single-cell analyses are being used to unravel many of the
      enduring mysteries that surround these diverse signaling pathways. 

PMID- 25605724
TI  - The inhibitor protein (IF1) of the F1F0-ATPase modulates human osteosarcoma cell
      bioenergetics.
AB  - The bioenergetics of IF1 transiently silenced cancer cells has been extensively
      investigated, but the role of IF1 (the natural inhibitor protein of F1F0-ATPase)
      in cancer cell metabolism is still uncertain. To shed light on this issue, we
      established a method to prepare stably IF1-silenced human osteosarcoma clones and
      explored the bioenergetics of IF1 null cancer cells. We showed that IF1-silenced
      cells proliferate normally, consume glucose, and release lactate as controls do,
      and contain a normal steady-state ATP level. However, IF1-silenced cells
      displayed an enhanced steady-state mitochondrial membrane potential and
      consistently showed a reduced ADP-stimulated respiration rate. In the parental
      cells (i.e. control cells containing IF1) the inhibitor protein was found to be
      associated with the dimeric form of the ATP synthase complex, therefore we
      propose that the interaction of IF1 with the complex either directly, by
      increasing the catalytic activity of the enzyme, or indirectly, by improving the
      structure of mitochondrial cristae, can increase the oxidative phosphorylation
      rate in osteosarcoma cells grown under normoxic conditions. 

PMID- 25605725
TI  - Mechanism of N-Acylthiourea-mediated activation of human histone deacetylase 8
      (HDAC8) at molecular and cellular levels.
AB  - We reported previously that an N-acylthiourea derivative (TM-2-51) serves as a
      potent and isozyme-selective activator for human histone deacetylase 8 (HDAC8).
      To probe the molecular mechanism of the enzyme activation, we performed a
      detailed account of the steady-state kinetics, thermodynamics, molecular
      modeling, and cell biology studies. The steady-state kinetic data revealed that
      TM-2-51 binds to HDAC8 at two sites in a positive cooperative manner. Isothermal
      titration calorimetric and molecular modeling data conformed to the two-site
      binding model of the enzyme-activator complex. We evaluated the efficacy of TM-2
      51 on SH-SY5Y and BE(2)-C neuroblastoma cells, wherein the HDAC8 expression has
      been correlated with cellular malignancy. Whereas TM-2-51 selectively induced
      cell growth inhibition and apoptosis in SH-SY5Y cells, it showed no such effects
      in BE(2)-C cells, and this discriminatory feature appears to be encoded in the
      p53 genotype of the above cells. Our mechanistic and cellular studies on HDAC8
      activation have the potential to provide insight into the development of novel
      anticancer drugs. 

PMID- 25605726
TI  - G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins from
      endosomes.
AB  - Some G protein-coupled receptors (GPCRs), in addition to activating
      heterotrimeric G proteins in the plasma membrane, appear to elicit a "second
      wave" of G protein activation after ligand-induced internalization. We briefly
      summarize evidence supporting this view and then discuss what is presently known
      about the functional significance of GPCR-G protein activation in endosomes.
      Endosomal activation can shape the cellular response temporally by prolonging its
      overall duration, and may shape the response spatially by moving the location of
      intracellular second messenger production relative to effectors. 

PMID- 25605727
TI  - Keratin 1 plays a critical role in golgi localization of core 2 N
      acetylglucosaminyltransferase M via interaction with its cytoplasmic tail.
AB  - Core 2 N-acetylglucosaminyltransferase 2/M (C2GnT-M) synthesizes all three
      beta6GlcNAc branch structures found in secreted mucins. Loss of C2GnT-M leads to
      development of colitis and colon cancer. Recently we have shown that C2GnT-M
      targets the Golgi at the Giantin site and is recycled by binding to non-muscle
      myosin IIA, a motor protein, via the cytoplasmic tail (CT). But how this enzyme
      is retained in the Golgi is not known. Proteomics analysis identifies keratin
      type II cytoskeletal 1 (KRT1) as a protein pulled down with anti-c-Myc antibody
      or C2GnT-M CT from the lysate of Panc1 cells expressing bC2GnT-M tagged with c
      Myc. Yeast two-hybrid analysis shows that the rod domain of KRT1 interacts
      directly with the WKR(6) motif in the C2GnT-M CT. Knockdown of KRT1 does not
      affect Golgi morphology but increases the interaction of C2GnT-M with non-muscle
      myosin IIA and its transportation to the endoplasmic reticulum, ubiquitination,
      and degradation. During Golgi recovery after brefeldin A treatment, C2GnT-M forms
      a complex with Giantin before KRT1, demonstrating CT-mediated sequential events
      of Golgi targeting and retention of C2GnT-M. In HeLa cells transiently expressing
      C2GnT-M-GFP, knockdown of KRT1 does not affect Golgi morphology but leaves C2GnT
      M outside of the Golgi, resulting in the formation of sialyl-T antigen.
      Interaction of C2GnT-M and KRT1 was also detected in the goblet cells of human
      colon epithelial tissue and primary culture of colonic epithelial cells. The
      results indicate that glycosylation and thus the function of glycoconjugates can
      be regulated by a protein that helps retain a glycosyltransferase in the Golgi. 

PMID- 25605728
TI  - Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) beta:
      LncRNA-hit-mediated TGFbeta-induced epithelial to mesenchymal transition in
      mammary epithelia.
AB  - Long noncoding RNAs (lncRNAs) are emerging as key regulators in various
      biological processes. Epithelial-to-mesenchymal transition (EMT) is a
      developmental process hijacked by tumor cells to depart from the primary tumor
      site, invade surrounding tissue, and establish distant metastases. Transforming
      growth factor beta (TGFbeta) signaling has been shown to be a major inducer of
      EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in
      this process remains largely unknown. Here we report a genome-wide lncRNA profile
      in mouse mammary epithelial NMuMG cells upon TGFbeta induction of EMT. Among
      10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the
      EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript
      induced by TGFbeta) mediates TGFbeta function, i.e. depletion of lncRNA-HIT
      inhibits TGFbeta-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is
      also significantly elevated in the highly metastatic 4T1 cells. Knockdown of
      lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth,
      and metastasis. E-cadherin was identified as a major target of lncRNA-HIT.
      Moreover, lncRNA-HIT is conserved in humans and elevated expression associates
      with more invasive human primary breast carcinoma. Collectively, these data
      suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in
      regulation of EMT and breast cancer invasion and metastasis, and could be
      potential therapeutic targets in breast cancers. 

PMID- 25605729
TI  - Structural and biochemical analysis of the essential diadenylate cyclase CdaA
      from Listeria monocytogenes.
AB  - The recently identified second messenger cyclic di-AMP (c-di-AMP) is involved in
      several important cellular processes, such as cell wall metabolism, maintenance
      of DNA integrity, ion transport, transcription regulation, and allosteric
      regulation of enzyme function. Interestingly, c-di-AMP is essential for growth of
      the Gram-positive model bacterium Bacillus subtilis. Although the genome of B.
      subtilis encodes three c-di-AMP-producing diadenlyate cyclases that can
      functionally replace each other, the phylogenetically related human pathogens
      like Listeria monocytogenes and Staphylococcus aureus possess only one enzyme,
      the diadenlyate cyclase CdaA. Because CdaA is also essential for growth of these
      bacteria, the enzyme is a promising target for the development of novel
      antibiotics. Here we present the first crystal structure of the L. monocytogenes
      CdaA diadenylate cyclase domain that is conserved in many human pathogens.
      Moreover, biochemical characterization of the cyclase revealed an unusual metal
      cofactor requirement. 

PMID- 25605730
TI  - Oncoprotein YAP regulates the spindle checkpoint activation in a mitotic
      phosphorylation-dependent manner through up-regulation of BubR1.
AB  - The transcriptional co-activator YAP (Yes-associated protein) functions as an
      oncogene; however, it is largely unclear how YAP exerts its oncogenic role. In
      this study, we further explored the functional significance of YAP and its
      mitotic phosphorylation in the spindle checkpoint. We found that the dynamic
      mitotic phosphorylation of YAP was CDC14-dependent. We also showed that YAP was
      required for the spindle checkpoint activation induced by spindle poisons.
      Mitotic phosphorylation of YAP was required for activation of the spindle
      checkpoint. Furthermore, enhanced expression of active YAP hyperactivated the
      spindle checkpoint and induced mitotic defects in a mitotic phosphorylation
      dependent manner. Mechanistically, we documented that mitotic phosphorylation of
      YAP controlled transcription of genes associated with the spindle checkpoint. YAP
      constitutively associated with BubR1 (BUB1-related protein kinase), and knockdown
      of BubR1 relieved YAP-driven hyperactivation of the spindle checkpoint. Finally,
      we demonstrated that YAP promoted epithelial cell invasion via both mitotic
      phosphorylation and BubR1-dependent mechanisms. Together, our results reveal a
      novel link between YAP and the spindle checkpoint and indicate a potential
      mechanism underlying the oncogenic function of YAP through dysregulation of the
      spindle checkpoint. 

PMID- 25605731
TI  - Metabolic fate of unsaturated glucuronic/iduronic acids from glycosaminoglycans:
      molecular identification and structure determination of streptococcal isomerase
      and dehydrogenase.
AB  - Glycosaminoglycans in mammalian extracellular matrices are degraded to their
      constituents, unsaturated uronic (glucuronic/iduronic) acids and amino sugars,
      through successive reactions of bacterial polysaccharide lyase and unsaturated
      glucuronyl hydrolase. Genes coding for glycosaminoglycan-acting lyase,
      unsaturated glucuronyl hydrolase, and the phosphotransferase system are assembled
      into a cluster in the genome of pathogenic bacteria, such as streptococci and
      clostridia. Here, we studied the streptococcal metabolic pathway of unsaturated
      uronic acids and the structure/function relationship of its relevant isomerase
      and dehydrogenase. Two proteins (gbs1892 and gbs1891) of Streptococcus agalactiae
      strain NEM316 were overexpressed in Escherichia coli, purified, and
      characterized. 4-Deoxy-l-threo-5-hexosulose-uronate (Dhu) nonenzymatically
      generated from unsaturated uronic acids was converted to 2-keto-3-deoxy-d
      gluconate via 3-deoxy-d-glycero-2,5-hexodiulosonate through successive reactions
      of gbs1892 isomerase (DhuI) and gbs1891 NADH-dependent reductase/dehydrogenase
      (DhuD). DhuI and DhuD enzymatically corresponded to 4-deoxy-l-threo-5-hexosulose
      uronate ketol-isomerase (KduI) and 2-keto-3-deoxy-d-gluconate dehydrogenase
      (KduD), respectively, involved in pectin metabolism, although no or low sequence
      identity was observed between DhuI and KduI or between DhuD and KduD,
      respectively. Genes for DhuI and DhuD were found to be included in the
      streptococcal genetic cluster, whereas KduI and KduD are encoded in clostridia.
      Tertiary and quaternary structures of DhuI and DhuD were determined by x-ray
      crystallography. Distinct from KduI beta-barrels, DhuI adopts an alpha/beta/alpha
      barrel structure as a basic scaffold similar to that of ribose 5-phosphate
      isomerase. The structure of DhuD is unable to accommodate the substrate/cofactor,
      suggesting that conformational changes are essential to trigger enzyme catalysis.
      This is the first report on the bacterial metabolism of glycosaminoglycan-derived
      unsaturated uronic acids by isomerase and dehydrogenase. 

PMID- 25605732
TI  - RFPL4A increases the G1 population and decreases sensitivity to chemotherapy in
      human colorectal cancer cells.
AB  - Cell cycle-arrested cancer cells are resistant to conventional chemotherapy that
      acts on the mitotic phases of the cell cycle, although the molecular mechanisms
      involved in halting cell cycle progression remain unclear. Here, we demonstrated
      that RFPL4A, an uncharacterized ubiquitin ligase, induced G1 retention and thus
      conferred decreased sensitivity to chemotherapy in the human colorectal cancer
      cell line, HCT116. Long term time lapse observations in HCT116 cells bearing a
      "fluorescence ubiquitin-based cell cycle indicator" identified a characteristic
      population that is viable but remains in the G1 phase for an extended period of
      time (up to 56 h). Microarray analyses showed that expression of RFPL4A was
      significantly up-regulated in these G1-arrested cells, not only in HCT116 cells
      but also in other cancer cell lines, and overexpression of RFPL4A increased the
      G1 population and decreased sensitivity to chemotherapy. However, knockdown of
      RFPL4A expression caused the cells to resume mitosis and induced their
      susceptibility to anti-cancer drugs in vitro and in vivo. These results indicate
      that RFPL4A is a novel factor that increases the G1 population and decreases
      sensitivity to chemotherapy and thus may be a promising therapeutic target for
      refractory tumor conditions. 

PMID- 25605733
TI  - Vaccinia virus protein A49 is an unexpected member of the B-cell Lymphoma (Bcl)-2
      protein family.
AB  - Vaccinia virus (VACV) encodes several proteins that inhibit activation of the
      proinflammatory transcription factor nuclear factor kappaB (NF-kappaB). VACV
      protein A49 prevents translocation of NF-kappaB to the nucleus by sequestering
      cellular beta-TrCP, a protein required for the degradation of the inhibitor of
      kappaB. A49 does not share overall sequence similarity with any protein of known
      structure or function. We solved the crystal structure of A49 from VACV Western
      Reserve to 1.8 A resolution and showed, surprisingly, that A49 has the same three
      dimensional fold as Bcl-2 family proteins despite lacking identifiable sequence
      similarity. Whereas Bcl-2 family members characteristically modulate cellular
      apoptosis, A49 lacks a surface groove suitable for binding BH3 peptides and does
      not bind proapoptotic Bcl-2 family proteins Bax or Bak. The N-terminal 17
      residues of A49 do not adopt a single well ordered conformation, consistent with
      their proposed role in binding beta-TrCP. Whereas pairs of A49 molecules interact
      symmetrically via a large hydrophobic surface in crystallo, A49 does not dimerize
      in solution or in cells, and we propose that this hydrophobic interaction surface
      may mediate binding to a yet undefined cellular partner. A49 represents the
      eleventh VACV Bcl-2 family protein and, despite these proteins sharing very low
      sequence identity, structure-based phylogenetic analysis shows that all poxvirus
      Bcl-2 proteins are structurally more similar to each other than they are to any
      cellular or herpesvirus Bcl-2 proteins. This is consistent with duplication and
      diversification of a single BCL2 family gene acquired by an ancestral poxvirus. 

PMID- 25605734
TI  - Down-regulation of the small conductance calcium-activated potassium channels in
      diabetic mouse atria.
AB  - The small conductance Ca(2+)-activated K(+) (SK) channels have recently been
      found to be expressed in the heart, and genome-wide association studies have
      shown that they are implicated in atrial fibrillation. Diabetes mellitus is an
      independent risk factor of atrial fibrillation, but the ionic mechanism
      underlying this relationship remains unclear. We hypothesized that SK channel
      function is abnormal in diabetes mellitus, leading to altered cardiac
      electrophysiology. We found that in streptozotocin-induced diabetic mice, the
      expression of SK2 and SK3 isoforms was down-regulated by 85 and 92%,
      respectively, whereas that of SK1 was not changed. SK currents from isolated
      diabetic mouse atrial myocytes were significantly reduced compared with controls.
      The resting potentials of isolated atrial preparations were similar between
      control and diabetic mice, but action potential durations were significantly
      prolonged in the diabetic atria. Exposure to apamin significantly prolonged
      action potential durations in control but not in diabetic atria. Production of
      reactive oxygen species was significantly increased in diabetic atria and in high
      glucose-cultured HL-1 cells, whereas exposure of HL-1 cells in normal glucose
      culture to H2O2 reduced the expression of SK2 and SK3. Tyrosine nitration in SK2
      and SK3 was significantly increased by high glucose culture, leading to
      accelerated channel turnover. Treatment with Tiron prevented these changes. Our
      results suggest that increased oxidative stress in diabetes results in SK channel
      associated electrical remodeling in diabetic atria and may promote
      arrhythmogenesis. 

PMID- 25605735
TI  - Mouse cytotoxic T cell-derived granzyme B activates the mitochondrial cell death
      pathway in a Bim-dependent fashion.
AB  - Cytotoxic T cells (Tc) use perforin and granzyme B (gzmB) to kill virus-infected
      cells and cancer cells. Recent evidence suggests that human gzmB primarily
      induces apoptosis via the intrinsic mitochondrial pathway by either cleaving Bid
      or activating Bim leading to the activation of Bak/Bax and subsequent generation
      of active caspase-3. In contrast, mouse gzmB is thought to predominantly induce
      apoptosis by directly processing pro-caspase-3. However, in certain mouse cell
      types gzmB-mediated apoptosis mainly occurs via the mitochondrial pathway. To
      investigate whether Bim is involved under the latter conditions, we have now
      employed ex vivo virus-immune mouse Tc that selectively kill by using perforin
      and gzmB (gzmB(+)Tc) as effector cells and wild type as well as Bim- or Bak/Bax
      deficient spontaneously (3T9) or virus-(SV40) transformed mouse embryonic
      fibroblast cells as targets. We show that gzmB(+)Tc-mediated apoptosis
      (phosphatidylserine translocation, mitochondrial depolarization, cytochrome c
      release, and caspase-3 activation) was severely reduced in 3T9 cells lacking
      either Bim or both Bak and Bax. This outcome was related to the ability of Tc
      cells to induce the degradation of Mcl-1 and Bcl-XL, the anti-apoptotic
      counterparts of Bim. In contrast, gzmB(+)Tc-mediated apoptosis was not affected
      in SV40-transformed mouse embryonic fibroblast cells lacking Bak/Bax. The data
      provide evidence that Bim participates in mouse gzmB(+)Tc-mediated apoptosis of
      certain targets by activating the mitochondrial pathway and suggest that the mode
      of cell death depends on the target cell. Our results suggest that the various
      molecular events leading to transformation and/or immortalization of cells have
      an impact on their relative resistance to the multiple gzmB(+)Tc-induced death
      pathways. 

PMID- 25605736
TI  - Quantitative analysis of purine nucleotides indicates that purinosomes increase
      de novo purine biosynthesis.
AB  - Enzymes in the de novo purine biosynthesis pathway are recruited to form a
      dynamic metabolic complex referred to as the purinosome. Previous studies have
      demonstrated that purinosome assembly responds to purine levels in culture
      medium. Purine-depleted medium or 2-dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole (DMAT) treatment stimulates the purinosome assembly in HeLa cells.
      Here, several metabolomic technologies were applied to quantify the static
      cellular levels of purine nucleotides and measure the de novo biosynthesis rate
      of IMP, AMP, and GMP. Direct comparison of purinosome-rich cells (cultured in
      purine-depleted medium) and normal cells showed a 3-fold increase in IMP
      concentration in purinosome-rich cells and similar levels of AMP, GMP, and ratios
      of AMP/GMP and ATP/ADP for both. In addition, a higher level of IMP was also
      observed in HeLa cells treated with DMAT. Furthermore, increases in the de novo
      IMP/AMP/GMP biosynthetic flux rate under purine-depleted condition were observed.
      The synthetic enzymes, adenylosuccinate synthase (ADSS) and inosine monophosphate
      dehydrogenase (IMPDH), downstream of IMP were also shown to be part of the
      purinosome. Collectively, these results provide further evidence that purinosome
      assembly is directly related to activated de novo purine biosynthesis, consistent
      with the functionality of the purinosome. 

PMID- 25605738
TI  - Adjuvant chemotherapy for rectal cancer after preoperative radiation or
      chemoradiation: one size does not fit all.

PMID- 25605737
TI  - GIV/Girdin transmits signals from multiple receptors by triggering trimeric G
      protein activation.
AB  - Activation of trimeric G proteins has been traditionally viewed as the exclusive
      job of G protein-coupled receptors (GPCRs). This view has been challenged by the
      discovery of non-receptor activators of trimeric G proteins. Among them, GIV
      (a.k.a. Girdin) is the first for which a guanine nucleotide exchange factor (GEF)
      activity has been unequivocally associated with a well defined motif. Here we
      discuss how GIV assembles alternative signaling pathways by sensing cues from
      various classes of surface receptors and relaying them via G protein activation.
      We also describe the dysregulation of this mechanism in disease and how its
      targeting holds promise for novel therapeutics. 

PMID- 25605739
TI  - Obesity and cancer: links with survival differ from those with incidence.

PMID- 25605740
TI  - The potential for epigenetic analysis of paediatric CNS tumours to improve
      diagnosis, treatment and prognosis.
AB  - Tumours of central nervous system (CNS) origin are the second most prevalent
      group of cancers in children, yet account for the majority of childhood cancer
      related deaths. Such tumours show diverse location, cell type of origin, disease
      course and long-term outcome, both across and within tumour types, making
      treatment problematic and contributing to the relatively modest progress in
      reducing mortality over recent decades. As technological advances begin to reveal
      the genetic landscape of all cancers, it is becoming increasingly clear that
      genetic disruption represents only one 'layer' of molecular disruption associated
      with disease aetiology. Obtaining a full understanding of tumour behaviour
      requires an understanding of the cellular and molecular pathways disrupted during
      tumourigenesis, particularly in relation to gene expression. The utility of such
      an approach has allowed stratification of cancers such as medulloblastoma into
      subgroups based on molecular features, with potential to refine risk prediction.
      Given that epigenetic disruption is a universal feature of all human cancers, it
      is logical to speculate that interrogating epigenetic marks may help to further
      define the molecular profile, and therefore the clinical trajectory, of tumours.
      An integrated approach to build a molecular 'signature' of individual tumours
      that incorporates traditional morphological and demographic information, genetic
      and transcriptome analysis, in addition to epigenomics (DNA methylation and non
      coding RNA analysis), offers tremendous promise to (i) inform treatment approach,
      (ii) facilitate accurate early identification (preferably at diagnosis) of
      variable risk groups (both good and poor prognosis groups), and (iii) track
      disease progression in childhood CNS tumours. 

PMID- 25605742
TI  - Postoperative surveillance in nonmetastatic colorectal cancer patients: yes,
      but...

PMID- 25605741
TI  - Bevacizumab continuation versus no continuation after first-line chemotherapy
      plus bevacizumab in patients with metastatic colorectal cancer: a randomized
      phase III non-inferiority trial (SAKK 41/06).
AB  - BACKGROUND: Chemotherapy plus bevacizumab is a standard option for first-line
      treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no
      continuation is non-inferior to continuation of bevacizumab after completing
      first-line chemotherapy. PATIENTS AND METHODS: In an open-label, phase III
      multicentre trial, patients with mCRC without disease progression after 4-6
      months of standard first-line chemotherapy plus bevacizumab were randomly
      assigned to continuing bevacizumab at a standard dose or no treatment. CT scans
      were done every 6 weeks until disease progression. The primary end point was time
      to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was
      chosen to detect a difference in TTP of 6 weeks or less, with a one-sided
      significance level of 10% and a statistical power of 85%. RESULTS: The intention
      to-treat population comprised 262 patients: median follow-up was 36.7 months. The
      median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab
      continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95%
      CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall
      survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR
      0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were
      uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation
      were estimated to be ~30,000 USD per patient. CONCLUSIONS: Non-inferiority could
      not be demonstrated for treatment holidays versus continuing bevacizumab
      monotheray, after 4-6 months of standard first-line chemotherapy plus
      bevacizumab. Based on no impact on overall survival and increased treatment
      costs, bevacizumab as a single agent is of no meaningful therapeutic value. More
      efficient treatment approaches are needed to maintain control of stabilized
      disease following induction therapy. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, number NCT00544700.

PMID- 25605743
TI  - Atypical femur fractures associated with use of bisphosphonates and denosumab.

PMID- 25605744
TI  - Genetics of breast cancer: a topic in evolution.
AB  - A hereditary predisposition to breast cancer significantly influences screening
      and follow-up recommendations for high-risk women. However, in patients with a
      suggestive personal and/or family history, a specific predisposing gene is
      identified in <30% of cases. Up to 25% of hereditary cases are due to a mutation
      in one of the few identified rare, but highly penetrant genes (BRCA1, BRCA2,
      PTEN, TP53, CDH1, and STK11), which confer up to an 80% lifetime risk of breast
      cancer. An additional 2%-3% of cases are due to a mutation in a rare, moderate
      penetrance gene (e.g. CHEK2, BRIP1, ATM, and PALB2), each associated with a
      twofold increase in risk. Prediction models suggest that there are unlikely to be
      additional yet to be identified high-penetrance genes. Investigation of common,
      low-penetrance alleles contributing to risk in a polygenic fashion has yielded a
      small number of suggestive single-nucleotide polymorphisms (SNPs), but the
      contributive risk of an individual SNP is quite small. Mutation testing is
      currently recommended for individual genes in the appropriate clinical setting
      where there is a high index of suspicion for a specific mutated gene or syndrome.
      Next-generation sequencing offers a new venue for risk assessment. At the present
      time, there are clear clinical guidelines for individuals with a mutation in a
      high-penetrance gene. Otherwise, standard models are used to predict an
      individual's lifetime risk by clinical and family history rather than genomic
      information. 

PMID- 25605745
TI  - Utility of 18fluoro-deoxyglucose positron emission tomography for prognosis and
      response assessments in a phase 2 study of romidepsin in patients with relapsed
      or refractory peripheral T-cell lymphoma.
AB  - BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), the value of
      (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for
      assessing prognosis and response to treatment remains unclear. The utility of FDG
      PET, in addition to conventional radiology, was examined as a planned exploratory
      end point in the pivotal phase 2 trial of romidepsin for the treatment of
      relapsed/refractory PTCL. PATIENTS AND METHODS: Patients received romidepsin at a
      dose of 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. The primary end point
      was the rate of confirmed/unconfirmed complete response (CR/CRu) as assessed by
      International Workshop Criteria (IWC) using conventional radiology. For the
      exploratory PET end point, patients with at least baseline FDG-PET scans were
      assessed by IWC + PET criteria. RESULTS: Of 130 patients, 110 had baseline FDG
      PET scans, and 105 were PET positive at baseline. The use of IWC + PET criteria
      increased the objective response rate to 30% compared with 26% by conventional
      radiology. Durations of response were well differentiated by both conventional
      radiology response criteria [CR/CRu versus partial response (PR), P = 0.0001] and
      PET status (negative versus positive, P < 0.0001). Patients who achieved CR/CRu
      had prolonged progression-free survival (PFS, median 25.9 months) compared with
      other response groups (P = 0.0007). Patients who achieved PR or stable disease
      (SD) had similar PFS (median 7.2 and 6.3 months, respectively, P = 0.6427). When
      grouping PR and SD patients by PET status, patients with PET-negative versus PET
      positive disease had a median PFS of 18.2 versus 7.1 months (P = 0.0923).
      CONCLUSIONS: Routine use of FDG-PET does not obviate conventional staging, but
      may aid in determining prognosis and refine response assessments for patients
      with PTCL, particularly for those who do not achieve CR/CRu by conventional
      staging. The optimal way to incorporate FDG-PET scans for patients with PTCL
      remains to be determined. TRIAL REGISTRATION: NCT00426764.

PMID- 25605747
TI  - How people feel their engagement can have efficacy for a bio-based society.
AB  - Up till now, the transition to a bio-based economy mainly involves expert
      stakeholders. However, the actions required are of a collective scale
      necessitating public engagement for support and action. Such engagement is only
      successful if members of the public believe their participation holds efficacy.
      This belief is closely linked to their personal representation of the issue. We
      report findings from our Q methodology workshop that explored public's efficacy
      beliefs on their perceived ways for engagement with a bio-based economy.
      Participants were provided with stakeholders' visual representations depicting a
      concourse of the transition to a bio-based economy for Q sorting. We found five
      efficacy beliefs that differ in scale on which participants consider themselves
      capable for action. These results indicate that members of the public foresee
      distinct and shared ways and levels in how they can engage with the transition to
      a bio-based society that do not always concur with stakeholders' views.

PMID- 25605748
TI  - A comparative analysis of media reporting of perceived risks and benefits of
      genetically modified crops and foods in Kenyan and international newspapers.
AB  - We empirically examine the reporting on biotechnology in Kenyan and international
      newspapers between 2010 and early 2014. We identify news articles that reported
      on biotechnology and analyze their use of words to determine whether there is a
      balance in the reporting of perceived risks and benefits. We also consider how
      the sources used in news articles and how the publication of the Seralini study
      of rats fed genetically modified maize affect the balance of reporting of
      perceived risks and benefits. We find that in Kenyan news reporting, more
      articles mention perceived benefits than risks, but when risks are mentioned, new
      articles contain more references to risks than to benefits. We also find that
      sources affect the reporting of perceived risks and benefits and that the
      Seralini study increased the likelihood that perceived risks are reported in
      Kenyan news reporting, but not in international newspapers. 

PMID- 25605746
TI  - Genetic lesions in diffuse large B-cell lymphomas.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults,
      accounting for 35%-40% of all cases. The combination of the anti-CD20 monoclonal
      antibody rituximab with anthracycline-based combination chemotherapy (R-CHOP,
      rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) lead to
      complete remission in most and can cure more than half of patients with DLBCL.
      The diversity in clinical presentation, as well as the pathologic and biologic
      heterogeneity, suggests that DLBCL comprises several disease entities that might
      ultimately benefit from different therapeutic approaches. In this review, we
      summarize the current literature focusing on the genetic lesions identified in
      DLBCL. 

PMID- 25605749
TI  - Public opinions about human enhancement can enhance the expert-only debate: A
      review study.
AB  - Human enhancement, the non-medical use of biomedical technologies to improve the
      human body or performance beyond their 'natural' limitations, is a growing trend.
      At the same time, the use of these technologies has societal consequences. In
      societal debates about human enhancement, however, it is mainly the voices of
      experts that are being heard, and little is known about the public's
      understanding of human enhancement. The views of the public can give valuable
      insights, and can, in turn, supplement experts' voices in political decision
      making as has been argued before for other emerging technologies. This study
      presents a systematic literature review of current public perceptions and
      attitudes towards technologies for human enhancement. Results show that the
      public's view has not been assessed often. Studies originate mainly from western
      oriented countries and cover a broad range of enhancement technologies. In the
      studies, the majority of respondents hold moderate to strong negative attitudes
      towards enhancement technologies for non-medical applications, although the type
      of technology influences these opinions. The study provides an overview of what
      is known about citizens' attitudes towards technologies for human enhancement.

PMID- 25605751
TI  - Consideration of comorbidity in treatment decision making in multidisciplinary
      cancer team meetings: a systematic review.
AB  - BACKGROUND: Comorbidity is very common among patients with cancer.
      Multidisciplinary team meetings (MDTs) are increasingly the context within which
      cancer treatment decisions are made internationally. Little is known about how
      comorbidity is considered, or impacts decisions, in MDTs. METHODS: A systematic
      literature review was conducted to evaluate previous evidence on consideration,
      and impact, of comorbidity in cancer MDT treatment decision making. Twenty-one
      original studies were included. RESULTS: Lack of information on comorbidity in
      MDTs impedes the ability of MDT members to make treatment recommendations, and
      for those recommendations to be implemented among patients with comorbidity.
      Where treatment is different from that recommended due to comorbidity, it is more
      conservative, despite evidence that such treatment may be tolerated and
      effective. MDT members are likely to be unaware of the extent to which issues
      such as comorbidity are ignored. CONCLUSIONS: MDTs should systematically consider
      treatment of patients with comorbidity. Further research is needed to assist
      clinicians to undertake MDT decision making that appropriately addresses
      comorbidity. If this were to occur, it would likely contribute to improved
      outcomes for cancer patients with comorbidities.

PMID- 25605750
TI  - Dysfunction of platelet-derived growth factor receptor alpha (PDGFRalpha)
      represses the production of oligodendrocytes from arylsulfatase A-deficient
      multipotential neural precursor cells.
AB  - The membrane-bound receptor for platelet-derived growth factor A (PDGFRalpha) is
      crucial for controlling the production of oligodendrocytes (OLs) for myelination,
      but regulation of its activity during OL differentiation is largely unknown. We
      have examined the effect of increased sulfated content of galactosylceramides
      (sulfatides) on the regulation of PDGFRalpha in multipotential neural precursors
      (NPs) that are deficient in arylsulfatase A (ASA) activity. This enzyme is
      responsible for the lysosomal hydrolysis of sulfatides. We show that sulfatide
      accumulation significantly impacts the formation of OLs via deregulation of
      PDGFRalpha function. PDGFRalpha is less associated with detergent-resistant
      membranes in ASA-deficient cells and showed a significant decrease in AKT
      phosphorylation. Rescue experiments with ASA showed a normalization of the ratio
      of long versus short sulfatides, restored PDGFRalpha levels, corrected its
      localization to detergent-resistant membranes, increased AKT phosphorylation, and
      normalized the production of OLs in ASA-deficient NPs. Moreover, our studies
      identified a novel mechanism that regulates the secretion of PDGFRalpha in NPs,
      in glial cells, and in the brain cortex via exosomal shedding. Our study provides
      a first step in understanding the role of sulfatides in regulating PDGFRalpha
      levels in OLs and its impact in myelination. 

PMID- 25605752
TI  - Licensing biotech intellectual property in university-industry partnerships.
AB  - Appropriate negotiation and drafting of license agreements are critical to
      successfully establishing and managing the expansive and complex relationships
      that are becoming more common between industry and universities. More often than
      not, the resulting licensing agreements become quite lengthy and complex, and the
      key principles become difficult to discern among all the details. This summary
      provides a short, nonexhaustive introduction to some of the essential components
      of these licenses with the intent of providing the non-licensing professional a
      better appreciation of some of the key commercial and legal terms from both an
      academic and company perspective, keeping in mind some of the considerations that
      particularly apply to biotechnology deals. 

PMID- 25605753
TI  - Gene Therapy for the Retinal Degeneration of Usher Syndrome Caused by Mutations
      in MYO7A.
AB  - Usher syndrome is a deaf-blindness disorder. One of the subtypes, Usher 1B, is
      caused by loss of function of the gene encoding the unconventional myosin, MYO7A.
      A variety of different viral-based delivery approaches have been tested for
      retinal gene therapy to prevent the blindness of Usher 1B, and a clinical trial
      based on one of these approaches has begun. This review evaluates the different
      approaches. 

PMID- 25605755
TI  - Existential Absence: The Lived Experience of Family Members During Their Older
      Loved One's Delirium.
AB  - When older people develop delirium, their demeanor changes; they often behave in
      ways that are out of character and seem to inhabit another world. Despite this,
      little is known about the experiences of family members who are with their older
      loved one at this time. This article reports a phenomenological study that
      involved in-depth interviews with 14 women whose older loved one had delirium.
      Analysis and interpretation of the data depict the women's experiences as
      "Changing family portraits: Sudden existential absence during delirium,"
      capturing the way family members lose the taken-for-granted presence of their
      familiar older loved one and confront a stranger during delirium. 

PMID- 25605754
TI  - Imaging in tuberculosis.
AB  - Despite many advances in both diagnosis and treatment, tuberculosis still remains
      one of commonest causes of morbidity and mortality from any infectious cause in
      the world. Although the overall incidence and mortality rate for tuberculosis has
      decreased over the years, timely and accurate diagnosis of tuberculosis is
      essential for the health of the patient as well as the public. For the diagnosis
      of tuberculosis, a high degree of clinical suspicion is required, and this
      becomes much more important in high-risk populations. Tuberculosis may masquerade
      as any disease; therefore, tissue and microbiological assessment is sometimes
      important for establishing the diagnosis. However, in daily practice, the
      clinician and radiologist should be familiar with the imaging features of
      pulmonary and extrapulmonary tuberculosis, as well as manifestations of
      tuberculosis in immunocompromised patients. Imaging provides a very important
      role in the diagnosis and management of tuberculosis. Although chest X rays
      remain the basic imaging modality for pulmonary tuberculosis, computed
      tomography, magnetic resonance imaging, and nuclear medicine techniques,
      including positron emission tomography/computed tomography, are extremely helpful
      in the assessment of both pulmonary and extrapulmonary tuberculosis. 

PMID- 25605756
TI  - Making the evidence (and arguments) count.

PMID- 25605758
TI  - An early endosome regulator, Rab5b, is an LRRK2 kinase substrate.
AB  - Leucine-rich repeat kinase 2 (LRRK2) has been identified as a causative gene for
      Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, both of
      which provide critical intracellular signal-transduction functions. We showed
      previously that Rab5b, a small GTPase protein that regulates the motility and
      fusion of early endosomes, interacts with LRRK2 and co-regulates synaptic vesicle
      endocytosis. Using recombinant proteins, we show here that LRRK2 phosphorylates
      Rab5b at its Thr6 residue in in vitro kinase assays with mass spectrophotometry
      analysis. Phosphorylation of Rab5b by LRRK2 on the threonine residue was
      confirmed by western analysis using cells stably expressing LRRK2 G2019S. The
      phosphomimetic T6D mutant exhibited stronger GTPase activity than that of the
      wild-type Rab5b. In addition, phosphorylation of Rab5b by LRRK2 also exhibited
      GTPase activity stronger than that of the unphosphorylated Rab5b protein. Two
      assays testing Rab5's activity, neurite outgrowth analysis and epidermal growth
      factor receptor degradation assays, showed that Rab5b T6D exhibited phenotypes
      that were expected to be observed in the inactive Rab5b, including longer neurite
      length and less degradation of EGFR. These results suggest that LRRK2 kinase
      activity functions as a Rab5b GTPase activating protein and thus, negatively
      regulates Rab5b signalling. 

PMID- 25605759
TI  - New roles of DNA and SopB in polymerization of SopA of Escherichia coli F
      plasmid.
AB  - Active equi-paritioning of the F plasmid is achieved by its sopABC gene. SopA
      binds to the sopAB promoter region and SopB binds to sopC. SopA also polymerizes
      in the presence of ATP and Mg(II), which is stimulated by SopB. Non-specific DNA
      is known to inhibit SopA polymerization and disassemble SopA polymer. This study
      followed kinetics of polymerization and de-polymerization of SopA by turbidity
      measurement and found new effects by DNA and SopB. Plasmid DNA, at low
      concentrations, shortened the lag (nucleation) phase of SopA polymerization and
      also caused an initial 'burst' of turbidity. Results with two non-specific 20-bp
      DNAs indicated sequence/length dependence of these effects. sopAB operator DNA
      only showed inhibition of SopA polymerization. Results of turbidity decrease of
      pre-formed SopA polymer in the presence of ethylenediaminetetraacetic acid showed
      that SopB also accelerates disassembly of the SopA polymer. The steady-state
      level of turbidity in the presence of SopB and plasmid DNA indicated synergy
      between SopB and DNA in the disassembly. SopB protein showed no effect on SopA
      polymerization, when SopB was specifically bound to DNA. This result and others
      with truncation mutants of SopB suggested that a proper configuration of the
      domains of SopB is important for SopA-SopB interactions. 

PMID- 25605760
TI  - Competitive science: is competition ruining science?
AB  - Science has always been a competitive undertaking. Despite recognition of the
      benefits of cooperation and team science, reduced availability of funding and
      jobs has made science more competitive than ever. Here we consider the benefits
      of competition in providing incentives to scientists and the adverse effects of
      competition on resource sharing, research integrity, and creativity. The history
      of science shows that transformative discoveries often occur in the absence of
      competition, which only emerges once fields are established and goals are
      defined. Measures to encourage collaboration and ameliorate competition in the
      scientific enterprise are discussed. 

PMID- 25605761
TI  - Interaction and assembly of two novel proteins in the spore wall of the
      microsporidian species Nosema bombycis and their roles in adherence to and
      infection of host cells.
AB  - Microsporidia are obligate intracellular parasites with rigid spore walls that
      protect against various environmental pressures. Despite an extensive description
      of the spore wall, little is known regarding the mechanism by which it is
      deposited or the role it plays in cell adhesion and infection. In this study, we
      report the identification and characterization of two novel spore wall proteins,
      SWP7 and SWP9, in the microsporidian species Nosema bombycis. SWP7 and SWP9 are
      mainly localized to the exospore and endospore of mature spores and the cytoplasm
      of sporonts, respectively. In addition, a portion of SWP9 is targeted to the
      spore wall of sporoblasts earlier than SWP7 is. Both SWP7 and SWP9 are
      specifically colocalized to the spore wall in mature spores. Furthermore,
      immunoprecipitation, far-Western blotting, unreduced SDS-PAGE, and yeast two
      hybrid data demonstrated that SWP7 interacted with SWP9. The chitin binding assay
      showed that, within the total spore protein, SWP9 and SWP7 can bind to the
      deproteinated chitin spore coats (DCSCs) of N. bombycis. However, binding of the
      recombinant protein rSWP7-His to the DCSCs is dependent on the combination of
      rSWP9-glutathione S-transferase (GST) with the DCSCs. Finally, rSWP9-GST, anti
      SWP9, and anti-SWP7 antibodies decreased spore adhesion and infection of the host
      cell. In conclusion, SWP7 and SWP9 may have important structural capacities and
      play significant roles in modulating host cell adherence and infection in vitro.
      A possible major function of SWP9 is as a scaffolding protein that supports other
      proteins (such as SWP7) that form the integrated spore wall of N. bombycis. 

PMID- 25605762
TI  - Burkholderia pseudomallei type III secretion system cluster 3 ATPase BsaS, a
      chemotherapeutic target for small-molecule ATPase inhibitors.
AB  - Melioidosis is an infectious disease of high mortality for humans and other
      animal species; it is prevalent in tropical regions worldwide. The pathogenesis
      of melioidosis depends on the ability of its causative agent, the Gram-negative
      bacterium Burkholderia pseudomallei, to enter and survive in host cells. B.
      pseudomallei can escape from the phagosome into the cytosol of phagocytic cells
      where it replicates and acquires actin-mediated motility, avoiding killing by the
      autophagy-dependent process, LC3 (microtubule-associated protein light chain 3)
      associated phagocytosis (LAP). The type III secretion system cluster 3 (TTSS3)
      facilitates bacterial escape from phagosomes, although the mechanism has not been
      fully elucidated. Given the recent identification of small-molecule inhibitors of
      the TTSS ATPase, we sought to determine the potential of the predicted TTSS3
      ATPase, encoded by bsaS, as a target for chemotherapeutic treatment of infection.
      A B. pseudomallei bsaS deletion mutant was generated and used as a control
      against which to assess the effect of inhibitor treatment. Infection of RAW 264.7
      cells with wild-type bacteria and subsequent treatment with the ATPase inhibitor
      compound 939 resulted in reduced intracellular bacterial survival, reduced escape
      from phagosomes, and increased colocalization with both LC3 and the lysosomal
      marker LAMP1 (lysosome-associated membrane protein 1). These changes were similar
      to those observed for infection of RAW 264.7 cells with the bsaS deletion mutant.
      We propose that treatment with the ATPase inhibitor compound 939 decreased
      intracellular bacterial survival through a reduced ability of bacteria to escape
      from phagosomes and increased killing via LAP. Therefore, small-molecule
      inhibitors of the TTSS3 ATPase have potential as therapeutic treatments against
      melioidosis. 

PMID- 25605763
TI  - Global analysis of posttranscriptional regulation by GlmY and GlmZ in
      enterohemorrhagic Escherichia coli O157:H7.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is a significant human pathogen and is
      the cause of bloody diarrhea and hemolytic-uremic syndrome. The virulence
      repertoire of EHEC includes the genes within the locus of enterocyte effacement
      (LEE) that are largely organized in five operons, LEE1 to LEE5, which encode a
      type III secretion system, several effectors, chaperones, and regulatory
      proteins. In addition, EHEC also encodes several non-LEE-encoded effectors and
      fimbrial operons. The virulence genes of this pathogen are under a large amount
      of posttranscriptional regulation. The small RNAs (sRNAs) GlmY and GlmZ activate
      the translation of glucosamine synthase (GlmS) in E. coli K-12, and in EHEC they
      destabilize the 3' fragments of the LEE4 and LEE5 operons and promote translation
      of the non-LEE-encoded effector EspFu. We investigated the global changes of EHEC
      gene expression governed by GlmY and GlmZ using RNA sequencing and gene arrays.
      This study extends the known effects of GlmY and GlmZ regulation to show that
      they promote expression of the curli adhesin, repress the expression of
      tryptophan metabolism genes, and promote the expression of acid resistance genes
      and the non-LEE-encoded effector NleA. In addition, seven novel EHEC-specific
      sRNAs were identified using RNA sequencing, and three of them--sRNA56, sRNA103,
      and sRNA350--were shown to regulate urease, fimbria, and the LEE, respectively.
      These findings expand the knowledge of posttranscriptional regulation in EHEC.

PMID- 25605765
TI  - Identification of ElpA, a Coxiella burnetii pathotype-specific Dot/Icm type IV
      secretion system substrate.
AB  - Coxiella burnetii causes human Q fever, a zoonotic disease that presents with
      acute flu-like symptoms and can result in chronic life-threatening endocarditis.
      In human alveolar macrophages, C. burnetii uses a Dot/Icm type IV secretion
      system (T4SS) to generate a phagolysosome-like parasitophorous vacuole (PV) in
      which to replicate. The T4SS translocates effector proteins, or substrates, into
      the host cytosol, where they mediate critical cellular events, including
      interaction with autophagosomes, PV formation, and prevention of apoptosis. Over
      100 C. burnetii Dot/Icm substrates have been identified, but the function of most
      remains undefined. Here, we identified a novel Dot/Icm substrate-encoding open
      reading frame (CbuD1884) present in all C. burnetii isolates except the Nine Mile
      reference isolate, where the gene is disrupted by a frameshift mutation,
      resulting in a pseudogene. The CbuD1884 protein contains two transmembrane
      helices (TMHs) and a coiled-coil domain predicted to mediate protein-protein
      interactions. The C-terminal region of the protein contains a predicted Dot/Icm
      translocation signal and was secreted by the T4SS, while the N-terminal portion
      of the protein was not secreted. When ectopically expressed in eukaryotic cells,
      the TMH-containing N-terminal region of the CbuD1884 protein trafficked to the
      endoplasmic reticulum (ER), with the C terminus dispersed nonspecifically in the
      host cytoplasm. This new Dot/Icm substrate is now termed ElpA (ER-localizing
      protein A). Full-length ElpA triggered substantial disruption of ER structure and
      host cell secretory transport. These results suggest that ElpA is a pathotype
      specific T4SS effector that influences ER function during C. burnetii infection. 

PMID- 25605764
TI  - Combinational deletion of three membrane protein-encoding genes highly attenuates
      yersinia pestis while retaining immunogenicity in a mouse model of pneumonic
      plague.
AB  - Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and
      MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and
      pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB
      acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene
      (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its
      lpp single and Deltalpp DeltamsbB double mutants. While the Deltaail single
      mutant was minimally attenuated compared to the WT bacterium in a mouse model of
      pneumonic plague, the Deltalpp Deltaail double mutant and the Deltalpp DeltamsbB
      Deltaail triple mutant were increasingly attenuated, with the latter being unable
      to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92.
      The mutant-infected animals developed balanced TH1- and TH2-based immune
      responses based on antibody isotyping. The triple mutant was cleared from mouse
      organs rapidly, with concurrent decreases in the production of various cytokines
      and histopathological lesions. When surviving animals infected with increasing
      doses of the triple mutant were subsequently challenged on day 24 with the
      bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived,
      with efficient clearing of the invading pathogen, as visualized in real time by
      in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT
      CO92, from animals was related to the decreased adherence and invasion of human
      derived HeLa and A549 alveolar epithelial cells and to its inability to survive
      intracellularly in these cells as well as in MH-S murine alveolar and primary
      human macrophages. An early burst of cytokine production in macrophages elicited
      by the triple mutant compared to WT CO92 and the mutant's sensitivity to the
      bactericidal effect of human serum would further augment bacterial clearance.
      Together, deletion of the ail gene from the Deltalpp DeltamsbB double mutant
      severely attenuated Y. pestis CO92 to evoke pneumonic plague in a mouse model
      while retaining the required immunogenicity needed for subsequent protection
      against infection. 

PMID- 25605766
TI  - Neither primary nor memory immunity to Mycobacterium tuberculosis infection is
      compromised in mice with chronic enteric helminth infection.
AB  - Previously we had reported that Nippostrongylus brasiliensis, a helminth with a
      lung migratory phase, affected host resistance against Mycobacterium tuberculosis
      infection through the induction of alternatively activated (M2) macrophages.
      Several helminth species do not have an obligatory lung migratory phase but
      establish chronic infections in the host that include potent immune
      downregulatory effects, in part mediated through induction of a FoxP3(+) T
      regulatory cell (Treg) response. Treg cells exhibit duality in their functions in
      host defense against M. tuberculosis infection since their depletion leads to
      enhanced priming of T cells in the lymph nodes and attendant improved control of
      M. tuberculosis infection, while their presence in the lung granuloma protects
      against excessive inflammation. Heligmosomoides polygyrus is a strictly murine
      enteric nematode that induces a strong FoxP3 Treg response in the host.
      Therefore, in this study we investigated whether host immunity to M. tuberculosis
      infection would be modulated in mice with chronic H. polygyrus infection. We
      report that neither primary nor memory immunity conferred by Mycobacterium bovis
      BCG vaccination was affected in mice with chronic enteric helminth infection,
      despite a systemic increase in FoxP3(+) T regulatory cells. The findings indicate
      that anti-M. tuberculosis immunity is not similarly affected by all helminth
      species and highlight the need to consider this inequality in human coinfection
      studies. 

PMID- 25605767
TI  - Role of the carboxy terminus of SecA in iron acquisition, protein translocation,
      and virulence of the bacterial pathogen Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a Gram-negative opportunistic nosocomial pathogen that
      causes pneumonia and soft tissue and systemic infections. Screening of a
      transposon insertion library of A. baumannii ATCC 19606T resulted in the
      identification of the 2010 derivative, which, although capable of growing well in
      iron-rich media, failed to prosper under iron chelation. Genetic, molecular, and
      functional assays showed that 2010's iron utilization-deficient phenotype is due
      to an insertion within the 3' end of secA, which results in the production of a C
      terminally truncated derivative of SecA. SecA plays a critical role in protein
      translocation through the SecYEG membrane channel. Accordingly, the secA mutation
      resulted in undetectable amounts of the ferric acinetobactin outer membrane
      receptor protein BauA while not affecting the production of other acinetobactin
      membrane protein transport components, such as BauB and BauE, or the secretion of
      acinetobactin by 2010 cells cultured in the presence of subinhibitory
      concentrations of the synthetic iron chelator 2,2'-dipyridyl. Outer membrane
      proteins involved in nutrient transport, adherence, and biofilm formation were
      also reduced in 2010. The SecA truncation also increased production of 30
      different proteins, including proteins involved in adaptation/tolerance
      responses. Although some of these protein changes could negatively affect the
      pathobiology of the 2010 derivative, its virulence defect is mainly due to its
      inability to acquire iron via the acinetobactin-mediated system. These results
      together indicate that although the C terminus of the A. baumannii ATCC 19606T
      SecA is not essential for viability, it plays a critical role in the production
      and translocation of different proteins and virulence.

PMID- 25605768
TI  - Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to
      opsonic activities of the pulmonary surfactant protein A.
AB  - Pseudomonas aeruginosa is a major bacterial pathogen commonly associated with
      chronic lung infections in cystic fibrosis (CF). Previously, we have demonstrated
      that the type IV pilus (Tfp) of P. aeruginosa mediates resistance to
      antibacterial effects of pulmonary surfactant protein A (SP-A). Interestingly, P.
      aeruginosa strains with group I pilins are O-glycosylated through the TfpO
      glycosyltransferase with a single subunit of O-antigen (O-ag). Importantly, TfpO
      mediated O-glycosylation is important for virulence in mouse lungs, exemplified
      by more frequent lung infection in CF with TfpO-expressing P. aeruginosa strains.
      However, the mechanism underlying the importance of Tfp glycosylation in P.
      aeruginosa pathogenesis is not fully understood. Here, we demonstrated one
      mechanism of increased fitness mediated by O-glycosylation of group 1 pilins on
      Tfp in the P. aeruginosa clinical isolate 1244. Using an acute pneumonia model in
      SP-A+/+ versus SP-A-/- mice, the O-glycosylation-deficient DeltatfpO mutant was
      found to be attenuated in lung infection. Both 1244 and DeltatfpO strains showed
      equal levels of susceptibility to SP-A-mediated membrane permeability. In
      contrast, the DeltatfpO mutant was more susceptible to opsonization by SP-A and
      by other pulmonary and circulating opsonins, SP-D and mannose binding lectin 2,
      respectively. Importantly, the increased susceptibility to phagocytosis was
      abrogated in the absence of opsonins. These results indicate that O-glycosylation
      of Tfp with O-ag specifically confers resistance to opsonization during host
      mediated phagocytosis.

PMID- 25605769
TI  - Ribonucleotide reductase NrdR as a novel regulator for motility and chemotaxis
      during adherent-invasive Escherichia coli infection.
AB  - A critical step in the life cycle of all organisms is the duplication of the
      genetic material during cell division. Ribonucleotide reductases (RNRs) are
      essential enzymes for this step because they control the de novo production of
      the deoxyribonucleotides required for DNA synthesis and repair.
      Enterobacteriaceae have three functional classes of RNRs (Ia, Ib, and III), which
      are transcribed from separate operons and encoded by the genes nrdAB, nrdHIEF,
      and nrdDG, respectively. Here, we investigated the role of RNRs in the virulence
      of adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease (CD)
      patients. Interestingly, the LF82 strain of AIEC harbors four different RNRs (two
      class Ia, one class Ib, and one class III). Although the E. coli RNR enzymes have
      been extensively characterized both biochemically and enzymatically, little is
      known about their roles during bacterial infection. We found that RNR expression
      was modified in AIEC LF82 bacteria during cell infection, suggesting that RNRs
      play an important role in AIEC virulence. Knockout of the nrdR and nrdD genes,
      which encode a transcriptional regulator of RNRs and class III anaerobic RNR,
      respectively, decreased AIEC LF82's ability to colonize the gut mucosa of
      transgenic mice that express human CEACAM6 (carcinoembryonic antigen-related cell
      adhesion molecule 6). Microarray experiments demonstrated that NrdR plays an
      indirect role in AIEC virulence by interfering with bacterial motility and
      chemotaxis. Thus, the development of drugs targeting RNR classes, in particular
      NrdR and NrdD, could be a promising new strategy to control gut colonization by
      AIEC bacteria in CD patients. 

PMID- 25605770
TI  - Apparent role for Borrelia burgdorferi LuxS during mammalian infection.
AB  - The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression
      patterns during its tick-mammal infection cycle. Earlier studies demonstrated
      that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI
      2]) and responds to AI-2 by measurably changing production of several infection
      associated proteins. luxS mutants, which are unable to produce AI-2, exhibit
      altered production of several proteins. B. burgdorferi cannot utilize the other
      product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not
      due to the absence of that molecule. Although a previous study found that a luxS
      mutant was capable of infecting mice, a critical caveat to those results is that
      bacterial loads were not quantified. To more precisely determine whether LuxS
      serves a role in mammalian infection, mice were simultaneously inoculated with
      congenic wild-type and luxS strains, and bacterial numbers were assessed using
      quantitative PCR. The wild-type bacteria substantially outcompeted the mutants,
      suggesting that LuxS performs a significant function during mammalian infection.
      These data also provide further evidence that nonquantitative infection studies
      do not necessarily provide conclusive results and that regulatory factors may not
      make all-or-none, black-or-white contributions to infectivity. 

PMID- 25605772
TI  - Cryptococcal phospholipase B1 is required for intracellular proliferation and
      control of titan cell morphology during macrophage infection.
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause
      of fungal-infection-related fatalities, especially in immunocompromised hosts.
      Several virulence factors are known to play a major role in the pathogenesis of
      cryptococcal infections, including the enzyme phospholipase B1 (Plb1). Compared
      to other well-studied Cryptococcus neoformans virulence factors such as the
      polysaccharide capsule and melanin production, very little is known about the
      contribution of Plb1 to cryptococcal virulence. Phospholipase B1 is a
      phospholipid-modifying enzyme that has been implicated in multiple stages of
      cryptococcal pathogenesis, including initiation and persistence of pulmonary
      infection and dissemination to the central nervous system, but the underlying
      reason for these phenotypes remains unknown. Here we demonstrate that a Deltaplb1
      knockout strain of C. neoformans has a profound defect in intracellular growth
      within host macrophages. This defect is due to a combination of a 50% decrease in
      proliferation and a 2-fold increase in cryptococcal killing within the phagosome.
      In addition, we show for the first time that the Deltaplb1 strain undergoes a
      morphological change during in vitro and in vivo intracellular infection,
      resulting in a subpopulation of very large titan cells, which may arise as a
      result of the attenuated mutant's inability to cope within the macrophage. 

PMID- 25605771
TI  - Selection for a CEACAM receptor-specific binding phenotype during Neisseria
      gonorrhoeae infection of the human genital tract.
AB  - Infections by Neisseria gonorrhoeae are increasingly common, are often caused by
      antibiotic-resistant strains, and can result in serious and lasting sequelae,
      prompting the reemergence of gonococcal disease as a leading global health
      concern. N. gonorrhoeae is a human-restricted pathogen that primarily colonizes
      urogenital mucosal surfaces. Disease progression varies greatly between the
      sexes: men usually present with symptomatic infection characterized by a painful
      purulent urethral discharge, while in women, the infection is often asymptomatic,
      with the most severe pathology occurring when the bacteria ascend from the lower
      genital tract into the uterus and fallopian tubes. Classical clinical studies
      demonstrated that clinically infectious strains uniformly express Opa adhesins;
      however, their specificities were unknown at the time. While in vitro studies
      have since identified CEACAM proteins as the primary target of Opa proteins, the
      gonococcal specificity for this human family of receptors has not been addressed
      in the context of natural infection. In this study, we characterize a collection
      of low-passage-number clinical-specimen-derived N. gonorrhoeae isolates for Opa
      expression and assess their CEACAM-binding profiles. We report marked in vivo
      selection for expression of phase-variable Opa proteins that bind CEACAM1 and
      CEACAM5 but selection against expression of Opa variants that bind to the
      neutrophil-restricted decoy receptor CEACAM3. This is the first study showing
      phenotypic selection for distinct CEACAM-binding phenotypes in vivo, and it
      supports the opposing functions of CEACAMs that facilitate infection versus
      driving inflammation within the genital tract. 

PMID- 25605774
TI  - Guidelines for reporting histopathology studies.

PMID- 25605773
TI  - Interleukin-10 from T cells, but not macrophages and granulocytes, is required
      for chronic disease in Leishmania mexicana infection.
AB  - Chronic cutaneous disease of mice caused by the protozoan parasite Leishmania
      mexicana requires interleukin-10 (IL-10) and FcgammaRIII (an activating IgG
      receptor). Macrophages readily secrete IL-10 in response to IgG-coated
      amastigotes, making macrophages a prime candidate as the critical source of IL
      10. However, indirect evidence suggested that macrophage IL-10 is not essential
      for chronic disease. I now show directly that mice lacking IL-10 from macrophages
      and granulocytes still have chronic disease, like wild-type C57BL/6 mice.
      However, T cell-derived IL-10 is required for chronic disease. CD4-cre IL
      10flox/flox mice lack IL-10 from T cells (both CD4+ and CD8+) and heal their L.
      mexicana lesions, with parasite control. I had previously shown that depletion of
      CD25+ T cells had no effect on chronic disease, and thus, T cells other than
      CD25+ regulatory T (Treg) cells should be the important source of IL-10. Given
      that conventional T cells do not express FcgammaRs, there is likely to be an
      indirect pathway by which FcgammaRIII on some other cell engaged by IgG1
      amastigote immune complexes induces IL-10 from T cells. Further work is needed to
      delineate these pathways.

PMID- 25605775
TI  - In vitro activity of 23 tea extractions and epigallocatechin gallate against
      Candida species.
AB  - In this study, we investigate the susceptibility of Candida albicans, Candida
      glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, and
      Aspergillus fumigatus using the EUCAST microdilution minimum inhibitory
      concentration (MIC) method (final tea supernatant concentration range 5.0-0.005
      mg/ml) to 23 different teas and tea catechins including epigallocatechin gallate
      (EGCG) isolated from green tea. All teas exhibited potent in vitro antifungal
      activity against C. glabrata. Six out of nine green teas and three of eight black
      teas had an MIC of 0.078 mg/ml, one white tea had an MIC of 0.156 mg/ml, and
      finally three of five oolong teas had an MIC of 0.156 mg/ml. Three teas exhibited
      activity against C. albicans (MIC 1.25 mg/ml), one green tea was active against
      C. parapsilosis (MIC 1.25 mg/ml), but none were effective against C. krusei, C.
      tropicalis or A. fumigatus at the concentrations tested. The MIC of EGCG was
      0.3125 MUg/ml against C. glabrata and 5.0 MUg/ml against C. albicans and C.
      parapsilosis. The effect was fungicidal against C. glabrata at higher
      concentrations. In conclusion, EGCG and other yet undefined substances in tea
      have differential antifungal activity in vitro against C. glabrata, C. albicans
      and C. parapsilosis. These data indicate that components of tea and EGCG might be
      useful particularly for the treatment of C. glabrata infections and warrants
      further investigations. 

PMID- 25605776
TI  - Reaching out--the many faces of science outreach.

PMID- 25605778
TI  - Building a plant: cell fate specification in the early Arabidopsis embryo.
AB  - Embryogenesis is the beginning of plant development, yet the cell fate decisions
      and patterning steps that occur during this time are reiterated during
      development to build the post-embryonic architecture. In Arabidopsis,
      embryogenesis follows a simple and predictable pattern, making it an ideal model
      with which to understand how cellular and tissue developmental processes are
      controlled. Here, we review the early stages of Arabidopsis embryogenesis,
      focusing on the globular stage, during which time stem cells are first specified
      and all major tissues obtain their identities. We discuss four different aspects
      of development: the formation of outer versus inner layers; the specification of
      vascular and ground tissues; the determination of shoot and root domains; and the
      establishment of the first stem cells. 

PMID- 25605777
TI  - Mathematically guided approaches to distinguish models of periodic patterning.
AB  - How periodic patterns are generated is an open question. A number of mechanisms
      have been proposed--most famously, Turing's reaction-diffusion model. However,
      many theoretical and experimental studies focus on the Turing mechanism while
      ignoring other possible mechanisms. Here, we use a general model of periodic
      patterning to show that different types of mechanism (molecular, cellular,
      mechanical) can generate qualitatively similar final patterns. Observation of
      final patterns is therefore not sufficient to favour one mechanism over others.
      However, we propose that a mathematical approach can help to guide the design of
      experiments that can distinguish between different mechanisms, and illustrate the
      potential value of this approach with specific biological examples.

PMID- 25605779
TI  - A plant U-box protein, PUB4, regulates asymmetric cell division and cell
      proliferation in the root meristem.
AB  - The root meristem (RM) is a fundamental structure that is responsible for
      postembryonic root growth. The RM contains the quiescent center (QC), stem cells
      and frequently dividing meristematic cells, in which the timing and the frequency
      of cell division are tightly regulated. In Arabidopsis thaliana, several gain-of
      function analyses have demonstrated that peptide ligands of the Clavata3
      (CLV3)/embryo surrounding region-related (CLE) family are important for
      maintaining RM size. Here, we demonstrate that a plant U-box E3 ubiquitin ligase,
      PUB4, is a novel downstream component of CLV3/CLE signaling in the RM. Mutations
      in PUB4 reduced the inhibitory effect of exogenous CLV3/CLE peptide on root cell
      proliferation and columella stem cell maintenance. Moreover, pub4 mutants grown
      without exogenous CLV3/CLE peptide exhibited characteristic phenotypes in the RM,
      such as enhanced root growth, increased number of cortex/endodermis stem cells
      and decreased number of columella layers. Our phenotypic and gene expression
      analyses indicated that PUB4 promotes expression of a cell cycle regulatory gene,
      CYCD6;1, and regulates formative periclinal asymmetric cell divisions in
      endodermis and cortex/endodermis initial daughters. These data suggest that PUB4
      functions as a global regulator of cell proliferation and the timing of
      asymmetric cell division that are important for final root architecture.

PMID- 25605780
TI  - A computational model for the coordination of neural progenitor self-renewal and
      differentiation through Hes1 dynamics.
AB  - Proper tissue development requires that stem/progenitor cells precisely
      coordinate cell division and differentiation in space and time. Notch-Hes1
      intercellular signaling, which affects both differentiation and cell cycle
      progression and directs cell fate decisions at various developmental stages in
      many cell types, is central to this process. This study explored whether the
      pattern of connections among the cell cycle regulatory module, the Notch effector
      Hes1 and the proneural factor Ngn2 could explain salient aspects of cell fate
      determination in neural progenitors. A mathematical model that includes mutual
      interactions between Hes1, Ngn2 and G1-phase regulators was constructed and
      simulated at the single- and two-cell levels. By differentially regulating G1
      phase progression, Hes1 and Ngn2 are shown to induce two contrasting cell cycle
      arrest states in early and late G1, respectively. Indeed, steady Hes1
      overexpression promotes reversible quiescence by downregulating activators of
      G0/G1 exit and Ngn2. Ngn2 also downregulates activators of G0/G1 exit, but
      cooperates with Cip/Kip proteins to prevent G1/S transit, whereby it promotes G1
      phase lengthening and, ultimately, contributes to reinforcing an irreversible
      late G1 arrest coincident with terminal differentiation. In this scheme, Hes1
      oscillation in single cells is able to maintain a labile proliferation state in
      dynamic balance with two competing cell fate outputs associated with Hes1
      mediated and Ngn2-mediated cell cycle arrest states. In Delta/Notch-connected
      cells, Hes1 oscillations and a lateral inhibition mechanism combine to establish
      heterogeneous Hes1, Ngn2 and cell cycle dynamics between proliferating neural
      progenitors, thereby increasing the chances of asymmetric cell fate decisions and
      improving the reliability of commitment to differentiation. 

PMID- 25605781
TI  - A transient wave of BMP signaling in the retina is necessary for Muller glial
      differentiation.
AB  - The primary glial cells in the retina, the Muller glia, differentiate from
      retinal progenitors in the first postnatal week. CNTF/LIF/STAT3 signaling has
      been shown to promote their differentiation; however, another key glial
      differentiation signal, BMP, has not been examined during this period of Muller
      glial differentiation. In the course of our analysis of the BMP signaling
      pathway, we observed a transient wave of Smad1/5/8 signaling in the inner nuclear
      layer at the end of the first postnatal week, from postnatal day (P) 5 to P9,
      after the end of neurogenesis. To determine the function of this transient wave,
      we blocked BMP signaling during this period in vitro or in vivo, using either a
      BMP receptor antagonist or noggin (Nog). Either treatment leads to a reduction in
      expression of the Muller glia-specific genes Rlbp1 and Glul, and the failure of
      many of the Muller glia to repress the bipolar/photoreceptor gene Otx2. These
      changes in normal Muller glial differentiation result in permanent disruption of
      the retina, including defects in the outer limiting membrane, rosette formation
      and a reduction in functional acuity. Our results thus show that Muller glia
      require a transient BMP signal at the end of neurogenesis to fully repress the
      neural gene expression program and to promote glial gene expression. 

PMID- 25605782
TI  - Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea.
AB  - Primary cilia have been implicated in the generation of planar cell polarity
      (PCP). However, variations in the severity of polarity defects in different cilia
      mutants, coupled with recent demonstrations of non-cilia-related actions of some
      cilia genes, make it difficult to determine the basis of these polarity defects.
      To address this issue, we evaluated PCP defects in cochlea from a selection of
      mice with mutations in cilia-related genes. Results indicated notable PCP
      defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and
      Ift20 single mutants that are more severe than in other cilia gene knockouts. In
      addition, deletion of either Bbs8 or Ift20 results in disruptions in asymmetric
      accumulation of the core PCP molecule Vangl2 in cochlear cells, suggesting a role
      for Bbs8 and/or Ift20, possibly upstream of core PCP asymmetry. Consistent with
      this, co-immunoprecipitation experiments indicate direct interactions of Bbs8 and
      Ift20 with Vangl2. We observed localization of Bbs and Ift proteins to
      filamentous actin as well as microtubules. This could implicate these molecules
      in selective trafficking of membrane proteins upstream of cytoskeletal
      reorganization, and identifies new roles for cilia-related proteins in cochlear
      PCP. 

PMID- 25605783
TI  - A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates
      fusion of primordia in the amniote face.
AB  - The mechanisms of morphogenesis are not well understood, yet shaping structures
      during development is essential for establishing correct organismal form and
      function. Here, we examine mechanisms that help to shape the developing face
      during the crucial period of facial primordia fusion. This period of development
      is a time when the faces of amniote embryos exhibit the greatest degree of
      similarity, and it probably results from the necessity for fusion to occur to
      establish the primary palate. Our results show that hierarchical induction
      mechanisms, consisting of iterative signaling by Sonic hedgehog (SHH) followed by
      Bone morphogenetic proteins (BMPs), regulate a dynamic expression pattern of Shh
      in the ectoderm covering the frontonasal (FNP) and maxillary (MxP) processes.
      Furthermore, this Shh expression domain contributes to the morphogenetic
      processes that drive the directional growth of the globular process of the FNP
      toward the lateral nasal process and MxP, in part by regulating cell
      proliferation in the facial mesenchyme. The nature of the induction mechanism
      that we discovered suggests that the process of fusion of the facial primordia is
      intrinsically buffered against producing maladaptive morphologies, such as clefts
      of the primary palate, because there appears to be little opportunity for
      variation to occur during expansion of the Shh expression domain in the ectoderm
      of the facial primordia. Ultimately, these results might explain why this period
      of development constitutes a phylotypic stage of facial development among
      amniotes. 

PMID- 25605784
TI  - SMAD2 and p38 signaling pathways act in concert to determine XY primordial germ
      cell fate in mice.
AB  - The sex of primordial germ cells (PGCs) is determined in developing gonads on the
      basis of cues from somatic cells. In XY gonads, sex-determining region Y (SRY)
      triggers fibroblast growth factor 9 (FGF9) expression in somatic cells. FGF
      signaling, together with downstream nodal/activin signaling, promotes male
      differentiation in XY germ cells by suppressing retinoic acid (RA)-dependent
      meiotic entry and inducing male-specific genes. However, the mechanism by which
      nodal/activin signaling regulates XY PGC fate is unknown. We uncovered the roles
      of SMAD2/3 and p38 MAPK, the putative downstream factors of nodal/activin
      signaling, in PGC sexual fate decision. We found that conditional deletion of
      Smad2, but not Smad3, from XY PGCs led to a loss of male-specific gene
      expression. Moreover, suppression of RA signaling did not rescue male-specific
      gene expression in Smad2-mutant testes, indicating that SMAD2 signaling promotes
      male differentiation in a RA-independent manner. By contrast, we found that p38
      signaling has an important role in the suppression of RA signaling. The Smad2
      deletion did not disrupt the p38 signaling pathway even though Nodal expression
      was significantly reduced, suggesting that p38 was not regulated by nodal
      signaling in XY PGCs. Additionally, the inhibition of p38 signaling in the Smad2
      mutant testes severely impeded XY PGC differentiation and induced meiosis. In
      conclusion, we propose a model in which p38 and SMAD2 signaling coordinate to
      determine the sexual fate of XY PGCs. 

PMID- 25605787
TI  - Inner workings: Malnutrition, gutted.

PMID- 25605786
TI  - CoinFLP: a system for efficient mosaic screening and for visualizing clonal
      boundaries in Drosophila.
AB  - Screens in mosaic Drosophila tissues that use chemical mutagenesis have
      identified many regulators of growth and patterning. Many of the mutant
      phenotypes observed were contingent upon the presence of both wild-type and
      mutant cells in the same tissue. More recently, large collections of RNAi lines
      or cDNAs expressed under Gal4/UAS control have been used to alter gene expression
      uniformly in specific tissues. However, these newer approaches are not easily
      combined with the efficient generation of genetic mosaics. The CoinFLP system
      described here enables mosaic screens in the context of gene knockdown or
      overexpression by automatically generating a reliable ratio of mutant to wild
      type tissue in a developmentally controlled manner. CoinFLP-Gal4 generates mosaic
      tissues composed of clones of which only a subset expresses Gal4. CoinFLP
      LexGAD/Gal4 generates tissues composed of clones that express either Gal4 or
      LexGAD, thus allowing the study of interactions between different types of
      genetically manipulated cells. By combining CoinFLP-LexGAD/Gal4 with the split
      GFP system GRASP, boundaries between genetically distinct cell populations can be
      visualized at high resolution. 

PMID- 25605789
TI  - Long-Term Balancing Selection in LAD1 Maintains a Missense Trans-Species
      Polymorphism in Humans, Chimpanzees, and Bonobos.
AB  - Balancing selection maintains advantageous genetic and phenotypic diversity in
      populations. When selection acts for long evolutionary periods selected
      polymorphisms may survive species splits and segregate in present-day populations
      of different species. Here, we investigate the role of long-term balancing
      selection in the evolution of protein-coding sequences in the Homo-Pan clade. We
      sequenced the exome of 20 humans, 20 chimpanzees, and 20 bonobos and detected
      eight coding trans-species polymorphisms (trSNPs) that are shared among the three
      species and have segregated for approximately 14 My of independent evolution.
      Although the majority of these trSNPs were found in three genes of the major
      histocompatibility locus cluster, we also uncovered one coding trSNP (rs12088790)
      in the gene LAD1. All these trSNPs show clustering of sequences by allele rather
      than by species and also exhibit other signatures of long-term balancing
      selection, such as segregating at intermediate frequency and lying in a locus
      with high genetic diversity. Here, we focus on the trSNP in LAD1, a gene that
      encodes for Ladinin-1, a collagenous anchoring filament protein of basement
      membrane that is responsible for maintaining cohesion at the dermal-epidermal
      junction; the gene is also an autoantigen responsible for linear IgA disease.
      This trSNP results in a missense change (Leucine257Proline) and, besides altering
      the protein sequence, is associated with changes in gene expression of LAD1. 

PMID- 25605785
TI  - A gene expression atlas of a bicoid-depleted Drosophila embryo reveals early
      canalization of cell fate.
AB  - In developing embryos, gene regulatory networks drive cells towards discrete
      terminal fates, a process called canalization. We studied the behavior of the
      anterior-posterior segmentation network in Drosophila melanogaster embryos by
      depleting a key maternal input, bicoid (bcd), and measuring gene expression
      patterns of the network at cellular resolution. This method results in a gene
      expression atlas containing the levels of mRNA or protein expression of 13 core
      patterning genes over six time points for every cell of the blastoderm embryo.
      This is the first cellular resolution dataset of a genetically perturbed
      Drosophila embryo that captures all cells in 3D. We describe the technical
      developments required to build this atlas and how the method can be employed and
      extended by others. We also analyze this novel dataset to characterize the degree
      and timing of cell fate canalization in the segmentation network. We find that in
      two layers of this gene regulatory network, following depletion of bcd,
      individual cells rapidly canalize towards normal cell fates. This result supports
      the hypothesis that the segmentation network directly canalizes cell fate, rather
      than an alternative hypothesis whereby cells are initially mis-specified and
      later eliminated by apoptosis. Our gene expression atlas provides a high
      resolution picture of a classic perturbation and will enable further
      computational modeling of canalization and gene regulation in this
      transcriptional network. 

PMID- 25605790
TI  - Epidemic Clones, Oceanic Gene Pools, and Eco-LD in the Free Living Marine
      Pathogen Vibrio parahaemolyticus.
AB  - We investigated global patterns of variation in 157 whole-genome sequences of
      Vibrio parahaemolyticus, a free-living and seafood associated marine bacterium.
      Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans,
      have spread globally. However, there are oceanic gene pools, one located in the
      oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination
      means that most isolates have acquired the genetic profile of their current
      location. We investigated the genetic structure in the Asian gene pool by
      calculating the effective population size in two different ways. Under standard
      neutral models, the two estimates should give similar answers but we found a 27
      fold difference. We propose that this discrepancy is caused by the subdivision of
      the species into a hundred or more ecotypes which are maintained stably in the
      population. To investigate the genetic factors involved, we used 51 unrelated
      isolates to conduct a genome-wide scan for epistatically interacting loci. We
      found a single example of strong epistasis between distant genome regions. A
      majority of strains had a type VI secretion system associated with bacterial
      killing. The remaining strains had genes associated with biofilm formation and
      regulated by cyclic dimeric GMP signaling. All strains had one or other of the
      two systems and none of isolate had complete complements of both systems,
      although several strains had remnants. Further "top down" analysis of patterns of
      linkage disequilibrium within frequently recombining species will allow a
      detailed understanding of how selection acts to structure the pattern of
      variation within natural bacterial populations. 

PMID- 25605791
TI  - Convergent evolution of ribonuclease h in LTR retrotransposons and retroviruses.
AB  - Ty3/Gypsy long terminals repeat (LTR) retrotransposons are structurally and
      phylogenetically close to retroviruses. Two notable structural differences
      between these groups of genetic elements are 1) the presence in retroviruses of
      an additional envelope gene, env, which mediates infection, and 2) a specific
      dual ribonuclease H (RNH) domain encoded by the retroviral pol gene. However,
      similar to retroviruses, many Ty3/Gypsy LTR retrotransposons harbor additional
      env-like genes, promoting concepts of the infective mode of these
      retrotransposons. Here, we provide a further line of evidence of similarity
      between retroviruses and some Ty3/Gypsy LTR retrotransposons. We identify that,
      together with their additional genes, plant Ty3/Gypsy LTR retrotransposons of the
      Tat group have a second RNH, as do retroviruses. Most importantly, we show that
      the resulting dual RNHs of Tat LTR retrotransposons and retroviruses emerged
      independently, providing strong evidence for their convergent evolution. The
      convergent resemblance of Tat LTR retrotransposons and retroviruses may indicate
      similar selection pressures acting on these diverse groups of elements and reveal
      potential evolutionary constraints on their structure. We speculate that dual RNH
      is required to accelerate retrotransposon evolution through increased rates of
      strand transfer events and subsequent recombination events. 

PMID- 25605792
TI  - limma powers differential expression analyses for RNA-sequencing and microarray
      studies.
AB  - limma is an R/Bioconductor software package that provides an integrated solution
      for analysing data from gene expression experiments. It contains rich features
      for handling complex experimental designs and for information borrowing to
      overcome the problem of small sample sizes. Over the past decade, limma has been
      a popular choice for gene discovery through differential expression analyses of
      microarray and high-throughput PCR data. The package contains particularly strong
      facilities for reading, normalizing and exploring such data. Recently, the
      capabilities of limma have been significantly expanded in two important
      directions. First, the package can now perform both differential expression and
      differential splicing analyses of RNA sequencing (RNA-seq) data. All the
      downstream analysis tools previously restricted to microarray data are now
      available for RNA-seq as well. These capabilities allow users to analyse both RNA
      seq and microarray data with very similar pipelines. Second, the package is now
      able to go past the traditional gene-wise expression analyses in a variety of
      ways, analysing expression profiles in terms of co-regulated sets of genes or in
      terms of higher-order expression signatures. This provides enhanced possibilities
      for biological interpretation of gene expression differences. This article
      reviews the philosophy and design of the limma package, summarizing both new and
      historical features, with an emphasis on recent enhancements and features that
      have not been previously described. 

PMID- 25605793
TI  - Identification of the target DNA sequence and characterization of DNA binding
      features of HlyU, and suggestion of a redox switch for hlyA expression in the
      human pathogen Vibrio cholerae from in silico studies.
AB  - HlyU, a transcriptional regulator common in many Vibrio species, activates the
      hemolysin gene hlyA in Vibrio cholerae, the rtxA1 operon in Vibrio vulnificus and
      the genes of plp-vah1 and rtxACHBDE gene clusters in Vibrio anguillarum. The
      protein is also proposed to be a potential global virulence regulator for V.
      cholerae and V. vulnificus. Mechanisms of gene control by HlyU in V. vulnificus
      and V. anguillarum are reported. However, detailed elucidation of the interaction
      of HlyU in V. cholerae with its target DNA at the molecular level is not
      available. Here we report a 17-bp imperfect palindrome sequence, 5'
      TAATTCAGACTAAATTA-3', 173 bp upstream of hlyA promoter, as the binding site of
      HlyU. This winged helix-turn-helix protein binds necessarily as a dimer with the
      recognition helices contacting the major grooves and the beta-sheet wings, the
      minor grooves. Such interactions enhance hlyA promoter activity in vivo.
      Mutations affecting dimerization as well as those in the DNA-protein interface
      hamper DNA binding and transcription regulation. Molecular dynamic simulations
      show hydrogen bonding patterns involving residues at the mutation sites and
      confirmed their importance in DNA binding. On binding to HlyU, DNA deviates by
      ~68o from linearity. Dynamics also suggest a possible redox control in HlyU. 

PMID- 25605794
TI  - Molecular mechanisms in DM1 - a focus on foci.
AB  - Myotonic dystrophy type 1 is caused by abnormal expansion of a CTG-trinucleotide
      repeat in the gene encoding Dystrophia Myotonica Protein Kinase (DMPK), which in
      turn leads to global deregulation of gene expression in affected individuals. The
      transcribed mRNA contains a massive CUG-expansion in the 3' untranslated region
      (3'UTR) facilitating nucleation of several regulatory RNA-binding proteins, which
      are thus unable to perform their normal cellular function. These CUG-expanded
      mRNA-protein aggregates form distinct, primarily nuclear foci. In differentiated
      muscle cells, most of the CUG-expanded RNA remains in the nuclear compartment,
      while in dividing cells such as fibroblasts a considerable fraction of the mutant
      RNA reaches the cytoplasm, consistent with findings that both nuclear and
      cytoplasmic events are mis-regulated in DM1. Recent evidence suggests that the
      nuclear aggregates, or ribonuclear foci, are more dynamic than previously
      anticipated and regulated by several proteins, including RNA helicases. In this
      review, we focus on the homeostasis of DMPK mRNA foci and discuss how their
      dynamic regulation may affect disease-causing mechanisms in DM1. 

PMID- 25605795
TI  - Evaluating the potential for undesired genomic effects of the piggyBac transposon
      system in human cells.
AB  - Non-viral transposons have been used successfully for genetic modification of
      clinically relevant cells including embryonic stem, induced pluripotent stem,
      hematopoietic stem and primary human T cell types. However, there has been
      limited evaluation of undesired genomic effects when using transposons for human
      genome modification. The prevalence of piggyBac(PB)-like terminal repeat (TR)
      elements in the human genome raises concerns. We evaluated if there were
      undesired genomic effects of the PB transposon system to modify human cells.
      Expression of the transposase alone revealed no mobilization of endogenous PB
      like sequences in the human genome and no increase in DNA double-strand breaks.
      The use of PB in a plasmid containing both transposase and transposon greatly
      increased the probability of transposase integration; however, using transposon
      and transposase from separate vectors circumvented this. Placing a eGFP transgene
      within transposon vector backbone allowed isolation of cells free from vector
      backbone DNA. We confirmed observable directional promoter activity within the
      5'TR element of PB but found no significant enhancer effects from the transposon
      DNA sequence. Long-term culture of primary human cells modified with eGFP
      transposons revealed no selective growth advantage of transposon-harboring cells.
      PB represents a promising vector system for genetic modification of human cells
      with limited undesired genomic effects. 

PMID- 25605796
TI  - Alternative splicing regulates the expression of G9A and SUV39H2
      methyltransferases, and dramatically changes SUV39H2 functions.
AB  - Alternative splicing is the main source of proteome diversity. Here, we have
      investigated how alternative splicing affects the function of two human histone
      methyltransferases (HMTase): G9A and SUV39H2. We show that exon 10 in G9A and
      exon 3 in SUV39H2 are alternatively included in a variety of tissues and cell
      lines, as well as in a different species. The production of these variants is
      likely tightly regulated because both constitutive and alternative splicing
      factors control their splicing profiles. Based on this evidence, we have assessed
      the link between the inclusion of these exons and the activity of both enzymes.
      We document that these HMTase genes yield several protein isoforms, which are
      likely issued from alternative splicing regulation. We demonstrate that inclusion
      of SUV39H2 exon 3 is a determinant of the stability, the sub-nuclear
      localization, and the HMTase activity. Genome-wide expression analysis further
      revealed that alternative inclusion of SUV39H2 exon 3 differentially modulates
      the expression of target genes. Our data also suggest that a variant of G9A may
      display a function that is independent of H3K9 methylation. Our work emphasizes
      that expression and function of genes are not collinear; therefore alternative
      splicing must be taken into account in any functional study. 

PMID- 25605797
TI  - Identification of protein complexes that bind to histone H3 combinatorial
      modifications using super-SILAC and weighted correlation network analysis.
AB  - The large number of chemical modifications that are found on the histone proteins
      of eukaryotic cells form multiple complex combinations, which can act as
      recognition signals for reader proteins. We have used peptide capture in
      conjunction with super-SILAC quantification to carry out an unbiased high
      throughput analysis of the composition of protein complexes that bind to histone
      H3K9/S10 and H3K27/S28 methyl-phospho modifications. The accurate quantification
      allowed us to perform Weighted correlation network analysis (WGCNA) to obtain a
      systems-level view of the histone H3 histone tail interactome. The analysis
      reveals the underlying modularity of the histone reader network with members of
      nuclear complexes exhibiting very similar binding signatures, which suggests that
      many proteins bind to histones as part of pre-organized complexes. Our results
      identify a novel complex that binds to the double H3K9me3/S10ph modification,
      which includes Atrx, Daxx and members of the FACT complex. The super-SILAC
      approach allows comparison of binding to multiple peptides with different
      combinations of modifications and the resolution of the WGCNA analysis is
      enhanced by maximizing the number of combinations that are compared. This makes
      it a useful approach for assessing the effects of changes in histone modification
      combinations on the composition and function of bound complexes. 

PMID- 25605798
TI  - A minimal ubiquitous chromatin opening element (UCOE) effectively prevents
      silencing of juxtaposed heterologous promoters by epigenetic remodeling in
      multipotent and pluripotent stem cells.
AB  - Epigenetic silencing of transgene expression represents a major obstacle for the
      efficient genetic modification of multipotent and pluripotent stem cells. We and
      others have demonstrated that a 1.5 kb methylation-free CpG island from the human
      HNRPA2B1-CBX3 housekeeping genes (A2UCOE) effectively prevents transgene
      silencing and variegation in cell lines, multipotent and pluripotent stem cells,
      and their differentiated progeny. However, the bidirectional promoter activity of
      this element may disturb expression of neighboring genes. Furthermore, the
      epigenetic basis underlying the anti-silencing effect of the UCOE on juxtaposed
      promoters has been only partially explored. In this study we removed the HNRPA2B1
      moiety from the A2UCOE and demonstrate efficient anti-silencing properties also
      for a minimal 0.7 kb element containing merely the CBX3 promoter. This DNA
      element largely prevents silencing of viral and tissue-specific promoters in
      multipotent and pluripotent stem cells. The protective activity of CBX3 was
      associated with reduced promoter CpG-methylation, decreased levels of repressive
      and increased levels of active histone marks. Moreover, the anti-silencing effect
      of CBX3 was locally restricted and when linked to tissue-specific promoters did
      not activate transcription in off target cells. Thus, CBX3 is a highly attractive
      element for sustained, tissue-specific and copy-number dependent transgene
      expression in vitro and in vivo. 

PMID- 25605799
TI  - A KALA-modified lipid nanoparticle containing CpG-free plasmid DNA as a potential
      DNA vaccine carrier for antigen presentation and as an immune-stimulative
      adjuvant.
AB  - Technologies that delivery antigen-encoded plasmid DNA (pDNA) to antigen
      presenting cell and their immune-activation are required for the success of DNA
      vaccines. Here we report on an artificial nanoparticle that can achieve these; a
      multifunctional envelope-type nanodevice modified with KALA, a peptide that forms
      alpha-helical structure at physiological pH (KALA-MEND). KALA modification and
      the removal of the CpG-motifs from the pDNA synergistically boosted transfection
      efficacy. In parallel, transfection with the KALA-MEND enhances the production of
      multiple cytokines and chemokines and co-stimulatory molecules via the Toll-like
      receptor 9-independent manner. Endosome-fusogenic lipid envelops and a long
      length of pDNA are essential for this immune stimulation. Furthermore,
      cytoplasmic dsDNA sensors that are related to the STING/TBK1 pathway and
      inflammasome are involved in IFN-beta and IL-1beta production, respectively.
      Consequently, the robust induction of antigen-specific cytotoxic T-lymphoma
      activity and the resulting prophylactic and therapeutic anti-tumor effect was
      observed in mice that had been immunized with bone marrow-derived dendritic cells
      ex vivo transfected with antigen-encoding pDNA. Collectively, the KALA-MEND
      possesses dual functions; gene transfection system and immune-stimulative
      adjuvant, those are both necessary for the successful DNA vaccine. 

PMID- 25605800
TI  - ARGONAUTE2 cooperates with SWI/SNF complex to determine nucleosome occupancy at
      human Transcription Start Sites.
AB  - Argonaute (AGO) proteins have a well-established role in post-transcriptional
      regulation of gene expression as key component of the RNA silencing pathways.
      Recent evidence involves AGO proteins in mammalian nuclear processes such as
      transcription and splicing, though the mechanistic aspects of AGO nuclear
      functions remain largely elusive. Here, by SILAC-based interaction proteomics, we
      identify the chromatin-remodelling complex SWI/SNF as a novel AGO2 interactor in
      human cells. Moreover, we show that nuclear AGO2 is loaded with a novel class of
      Dicer-dependent short RNAs (sRNAs), that we called swiRNAs, which map nearby the
      Transcription Start Sites (TSSs) bound by SWI/SNF. The knock-down of AGO2
      decreases nucleosome occupancy at the first nucleosome located downstream of TSSs
      in a swiRNA-dependent manner. Our findings indicate that in human cells AGO2
      binds SWI/SNF and a novel class of sRNAs to establish nucleosome occupancy on
      target TSSs. 

PMID- 25605801
TI  - Bacterial global regulators DksA/ppGpp increase fidelity of transcription.
AB  - Collisions between paused transcription elongation complexes and replication
      forks inevitably happen, which may lead to collapse of replication fork and could
      be detrimental to cells. Bacterial transcription factor DksA and its cofactor
      alarmone ppGpp were proposed to contribute to prevention of such collisions,
      although the mechanism of this activity remains elusive. Here we show that
      DksA/ppGpp do not destabilise transcription elongation complexes or inhibit their
      backtracking, as was proposed earlier. Instead, we show, both in vitro and in
      vivo, that DksA/ppGpp increase fidelity of transcription elongation by slowing
      down misincorporation events. As misincorporation events cause temporary pauses,
      contribution to fidelity suggests the mechanism by which DksA/ppGpp contribute to
      prevention of collisions of transcription elongation complexes with replication
      forks. DksA is only the second known accessory factor, after transcription factor
      Gre, that increases fidelity of RNA synthesis in bacteria. 

PMID- 25605802
TI  - BMP4 and BMP Antagonists Regulate Human White and Beige Adipogenesis.
AB  - The limited expandability of subcutaneous adipose tissue, due to reduced ability
      to recruit and differentiate new adipocytes, prevents its buffering effect in
      obesity and is characterized by expanded adipocytes (hypertrophic obesity). Bone
      morphogenetic protein-4 (BMP4) plays a key role in regulating adipogenic
      precursor cell commitment and differentiation. We found BMP4 to be induced and
      secreted by differentiated (pre)adipocytes, and BMP4 was increased in large
      adipose cells. However, the precursor cells exhibited a resistance to BMP4 owing
      to increased secretion of the BMP inhibitor Gremlin-1 (GREM1). GREM1 is secreted
      by (pre)adipocytes and is an inhibitor of both BMP4 and BMP7. BMP4 alone, and/or
      silencing GREM1, increased transcriptional activation of peroxisome proliferator
      activated receptor gamma and promoted the preadipocytes to assume an oxidative
      beige/brown adipose phenotype including markers of increased mitochondria and
      PGC1alpha. Driving white adipose differentiation inhibited the beige/brown
      markers, suggesting the presence of multipotent adipogenic precursor cells.
      However, silencing GREM1 and/or adding BMP4 during white adipogenic
      differentiation reactivated beige/brown markers, suggesting that increased BMP4
      preferentially regulates the beige/brown phenotype. Thus, BMP4, secreted by white
      adipose cells, is an integral feedback regulator of both white and beige
      adipogenic commitment and differentiation, and resistance to BMP4 by GREM1
      characterizes hypertrophic obesity. 

PMID- 25605803
TI  - Regulation of glucose tolerance and sympathetic activity by MC4R signaling in the
      lateral hypothalamus.
AB  - Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological
      functions, including energy balance, glucose homeostasis, and autonomic activity.
      Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to
      receive input from leptin-responsive arcuate proopiomelanocortin neurons, the
      physiological functions of MC4Rs in the LHA are incompletely understood. We
      report that MC4R(LHA) signaling regulates glucose tolerance and sympathetic nerve
      activity. Restoring expression of MC4Rs specifically in the LHA improves glucose
      intolerance in obese MC4R-null mice without affecting body weight or circulating
      insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake
      identifies the interscapular brown adipose tissue (iBAT) as a primary source
      where glucose uptake is increased in MC4R(LHA) mice. Direct multifiber
      sympathetic nerve recording further reveals that sympathetic traffic to iBAT is
      significantly increased in MC4R(LHA) mice, which accompanies a significant
      elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation
      prevents the glucoregulatory effect of MC4R(LHA) signaling. These results
      identify a novel role for MC4R(LHA) signaling in the control of sympathetic nerve
      activity and glucose tolerance independent of energy balance.

PMID- 25605805
TI  - Distinct roles of beta-cell mass and function during type 1 diabetes onset and
      remission.
AB  - Cure of type 1 diabetes (T1D) by immune intervention at disease onset depends on
      the restoration of insulin secretion by endogenous beta-cells. However, little is
      known about the potential of beta-cell mass and function to recover after
      autoimmune attack ablation. Using a longitudinal in vivo imaging approach, we
      show how functional status and mass of beta-cells adapt in response to the onset
      and remission of T1D. We demonstrate that infiltration reduces beta-cell mass
      prior to onset and, together with emerging hyperglycemia, affects beta-cell
      function. After immune intervention, persisting hyperglycemia prevents functional
      recovery but promotes beta-cell mass increase in mouse islets. When blood glucose
      levels return to normoglycemia beta-cell mass expansion stops, and subsequently
      glucose tolerance recovers in combination with beta-cell function. Similar to
      mouse islets, human islets exhibit cell exhaustion and recovery in response to
      transient hyperglycemia. However, the effect of hyperglycemia on human islet mass
      increase is minor and transient. Our data demonstrate a major role of functional
      exhaustion and recovery of beta-cells during T1D onset and remission. Therefore,
      these findings support early intervention therapy for individuals with T1D.

PMID- 25605804
TI  - Hypohalous acids contribute to renal extracellular matrix damage in experimental
      diabetes.
AB  - In diabetes, toxic oxidative pathways are triggered by persistent hyperglycemia
      and contribute to diabetes complications. A major proposed pathogenic mechanism
      is the accumulation of protein modifications that are called advanced glycation
      end products. However, other nonenzymatic post-translational modifications may
      also contribute to pathogenic protein damage in diabetes. We demonstrate that
      hypohalous acid-derived modifications of renal tissues and extracellular matrix
      (ECM) proteins are significantly elevated in experimental diabetic nephropathy.
      Moreover, diabetic renal ECM shows diminished binding of alpha1beta1 integrin
      consistent with the modification of collagen IV by hypochlorous (HOCl) and
      hypobromous acids. Noncollagenous (NC1) hexamers, key connection modules of
      collagen IV networks, are modified via oxidation and chlorination of tryptophan
      and bromination of tyrosine residues. Chlorotryptophan, a relatively minor
      modification, has not been previously found in proteins. In the NC1 hexamers
      isolated from diabetic kidneys, levels of HOCl-derived oxidized and chlorinated
      tryptophan residues W(28) and W(192) are significantly elevated compared with
      nondiabetic controls. Molecular dynamics simulations predicted a more relaxed NC1
      hexamer tertiary structure and diminished assembly competence in diabetes; this
      was confirmed using limited proteolysis and denaturation/refolding. Our results
      suggest that hypohalous acid-derived modifications of renal ECM, and specifically
      collagen IV networks, contribute to functional protein damage in diabetes.

PMID- 25605806
TI  - Dipeptidyl peptidase-4 inhibition ameliorates Western diet-induced hepatic
      steatosis and insulin resistance through hepatic lipid remodeling and modulation
      of hepatic mitochondrial function.
AB  - Novel therapies are needed for treating the increasing prevalence of hepatic
      steatosis in Western populations. In this regard, dipeptidyl peptidase-4 (DPP-4)
      inhibitors have recently been reported to attenuate the development of hepatic
      steatosis, but the potential mechanisms remain poorly defined. In the current
      study, 4-week-old C57Bl/6 mice were fed a high-fat/high-fructose Western diet
      (WD) or a WD containing the DPP-4 inhibitor, MK0626, for 16 weeks. The DPP-4
      inhibitor prevented WD-induced hepatic steatosis and reduced hepatic insulin
      resistance by enhancing insulin suppression of hepatic glucose output. WD-induced
      accumulation of hepatic triacylglycerol (TAG) and diacylglycerol (DAG) content
      was significantly attenuated with DPP-4 inhibitor treatment. In addition, MK0626
      significantly reduced mitochondrial incomplete palmitate oxidation and increased
      indices of pyruvate dehydrogenase activity, TCA cycle flux, and hepatic TAG
      secretion. Furthermore, DPP-4 inhibition rescued WD-induced decreases in hepatic
      PGC-1alpha and CPT-1 mRNA expression and hepatic Sirt1 protein content. Moreover,
      plasma uric acid levels in mice fed the WD were decreased after MK0626 treatment.
      These studies suggest that DPP-4 inhibition ameliorates hepatic steatosis and
      insulin resistance by suppressing hepatic TAG and DAG accumulation through
      enhanced mitochondrial carbohydrate utilization and hepatic TAG secretion/export
      with a concomitant reduction of uric acid production.

PMID- 25605807
TI  - Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and
      Angiogenesis.
AB  - Endostatin is a well-known angiogenesis inhibitor. Although angiogenesis has been
      considered as a potential therapeutic target of obesity, the inhibitory effect of
      endostatin on adipogenesis and dietary-induced obesity has never been
      demonstrated. Adipogenesis plays a critical role in controlling adipocyte cell
      number, body weight, and metabolic profile in a homeostatic state. Here we reveal
      that endostatin inhibits adipogenesis and dietary-induced obesity. The
      antiadipogenic mechanism of endostatin lies in its interaction with Sam68 RNA
      binding protein in the nuclei of preadipocytes. This interaction competitively
      impairs the binding of Sam68 to intron 5 of mammalian target of rapamycin (mTOR),
      causing an error in mTOR transcript. This consequently decreases the expression
      of mTOR, results in decreased activities of the mTOR complex 1 pathway, and leads
      to defects in adipogenesis. Moreover, our findings demonstrate that the
      antiangiogenic function of endostatin also contributes to its obesity-inhibitory
      activity. Through the combined functions on adipogenesis and angiogenesis,
      endostatin prevents dietary-induced obesity and its related metabolic disorders,
      including insulin resistance, glucose intolerance, and hepatic steatosis. Thus,
      our findings reveal that endostatin has a potential application for antiobesity
      therapy and the prevention of obesity-related metabolic syndromes. 

PMID- 25605808
TI  - A novel role for subcutaneous adipose tissue in exercise-induced improvements in
      glucose homeostasis.
AB  - Exercise training improves whole-body glucose homeostasis through effects largely
      attributed to adaptations in skeletal muscle; however, training also affects
      other tissues, including adipose tissue. To determine whether exercise-induced
      adaptations to adipose tissue contribute to training-induced improvements in
      glucose homeostasis, subcutaneous white adipose tissue (scWAT) from exercise
      trained or sedentary donor mice was transplanted into the visceral cavity of
      sedentary recipients. Remarkably, 9 days post-transplantation, mice receiving
      scWAT from exercise-trained mice had improved glucose tolerance and enhanced
      insulin sensitivity compared with mice transplanted with scWAT from sedentary or
      sham-treated mice. Mice transplanted with scWAT from exercise-trained mice had
      increased insulin-stimulated glucose uptake in tibialis anterior and soleus
      muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted
      endocrine effects. Furthermore, the deleterious effects of high-fat feeding on
      glucose tolerance and insulin sensitivity were completely reversed if high-fat
      fed recipient mice were transplanted with scWAT from exercise-trained mice. In
      additional experiments, voluntary exercise training by wheel running for only 11
      days resulted in profound changes in scWAT, including the increased expression of
      ~1,550 genes involved in numerous cellular functions including metabolism.
      Exercise training causes adaptations to scWAT that elicit metabolic improvements
      in other tissues, demonstrating a previously unrecognized role for adipose tissue
      in the beneficial effects of exercise on systemic glucose homeostasis.

PMID- 25605809
TI  - Defects in mitochondrial efficiency and H2O2 emissions in obese women are
      restored to a lean phenotype with aerobic exercise training.
AB  - The notion that mitochondria contribute to obesity-induced insulin resistance is
      highly debated. Therefore, we determined whether obese (BMI 33 kg/m(2)), insulin
      resistant women with polycystic ovary syndrome had aberrant skeletal muscle
      mitochondrial physiology compared with lean, insulin-sensitive women (BMI 23
      kg/m(2)). Maximal whole-body and mitochondrial oxygen consumption were not
      different between obese and lean women. However, obese women exhibited lower
      mitochondrial coupling and phosphorylation efficiency and elevated mitochondrial
      H2O2 (mtH2O2) emissions compared with lean women. We further evaluated the impact
      of 12 weeks of aerobic exercise on obesity-related impairments in insulin
      sensitivity and mitochondrial energetics in the fasted state and after a high-fat
      mixed meal. Exercise training reversed obesity-related mitochondrial derangements
      as evidenced by enhanced mitochondrial bioenergetics efficiency and decreased
      mtH2O2 production. A concomitant increase in catalase antioxidant activity and
      decreased DNA oxidative damage indicate improved cellular redox status and a
      potential mechanism contributing to improved insulin sensitivity. mtH2O2
      emissions were refractory to a high-fat meal at baseline, but after exercise,
      mtH2O2 emissions increased after the meal, which resembles previous findings in
      lean individuals. We demonstrate that obese women exhibit impaired mitochondrial
      bioenergetics in the form of decreased efficiency and impaired mtH2O2 emissions,
      while exercise effectively restores mitochondrial physiology toward that of lean,
      insulin-sensitive individuals.

PMID- 25605810
TI  - Association analysis of 29,956 individuals confirms that a low-frequency variant
      at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion.
AB  - A recent study identified a low-frequency variant at CCND2 associated with lower
      risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher
      height, and, paradoxically, higher BMI. We aimed to replicate the strength and
      effect size of these associations in independent samples and to assess the
      underlying mechanism. We genotyped the variant in 29,956 individuals and tested
      its association with type 2 diabetes and related traits. The low-frequency allele
      was associated with a lower risk of type 2 diabetes (OR 0.53; P = 2 * 10(-13);
      6,647 case vs. 12,645 control subjects), higher disposition index (beta = 0.07
      log10; P = 2 * 10(-11); n = 13,028), and higher Matsuda index of insulin
      sensitivity (beta = 0.02 log10; P = 5 * 10(-3); n = 13,118) but not fasting
      proinsulin (beta = 0.01 log10; P = 0.5; n = 6,985). The low frequency allele was
      associated with higher adult height (beta = 1.38 cm; P = 6 * 10(-9); n = 13,927),
      but the association of the variant with BMI (beta = 0.36 kg/m(2); P = 0.02; n =
      24,807), estimated in four population-based samples, was less than in the
      original publication where the effect estimate was biased by analyzing case
      subjects with type 2 diabetes and control subjects without diabetes separately.
      Our study establishes that a low-frequency allele in CCND2 halves the risk of
      type 2 diabetes primarily through enhanced insulin secretion.

PMID- 25605811
TI  - Are pre-existing markers of chronic kidney disease associated with short-term
      mortality following acute community-acquired pneumonia and sepsis? A cohort study
      among older people with diabetes using electronic health records.
AB  - BACKGROUND: We aimed to examine whether pre-existing impaired estimated
      glomerular filtration rate (eGFR) and proteinuria were associated with mortality
      following community-acquired pneumonia or sepsis among people aged >= 65 years
      with diabetes mellitus, without end-stage renal disease. METHODS: Patients were
      followed up from onset of first community-acquired pneumonia or sepsis episode in
      a cohort study using large, linked electronic health databases. Follow-up was for
      up to 90 days, unlimited by hospital discharge. We used generalized linear models
      with log link, normal distribution and robust standard errors to calculate risk
      ratios (RRs) for all-cause 28- and 90-day mortality according to two markers of
      chronic kidney disease: eGFR and proteinuria. RESULTS: All-cause mortality among
      the 4743 patients with pneumonia was 29.6% after 28 days and 37.4% after 90 days.
      Among the 1058 patients with sepsis, all-cause 28- and 90-day mortality were 35.6
      and 44.2%, respectively. eGFR <30 mL/min/1.73 m(2) was a risk marker of higher 28
      day mortality for pneumonia (RR 1.27: 95% CI 1.12-1.43) and sepsis (RR 1.32: 95%
      CI 1.07-1.64), adjusted for age, sex, socio-economic status, smoking status and
      co-morbidities. Neither moderately impaired eGFR nor proteinuria were associated
      with short-term mortality following either infection. CONCLUSIONS: People with
      pre-existing low eGFR but not on dialysis are at higher risk of death following
      pneumonia and sepsis. This association was not explained by existing co
      morbidities. These patients need to be carefully monitored to prevent modifiable
      causes of death.

PMID- 25605812
TI  - The effect of a Diabetes-Specific Cognitive Behavioral Treatment Program (DIAMOS)
      for patients with diabetes and subclinical depression: results of a randomized
      controlled trial.
AB  - OBJECTIVE: Subclinical depression is one of the most frequent mental
      comorbidities in patients with diabetes and is associated with a poorer long-term
      prognosis. Since there is a lack of specific intervention concepts for this
      patient group, a self-management-oriented group program (DIAMOS [Diabetes
      Motivation Strengthening]) was newly developed and evaluated in a randomized
      trial. RESEARCH DESIGN AND METHODS: DIAMOS is composed of cognitive behavioral
      interventions aiming at the reduction of diabetes distress. The active control
      group (CG) received diabetes education. The primary outcome was depressive
      symptoms. Secondary outcomes were diabetes distress, well-being, self-care
      behavior, diabetes acceptance, diabetes treatment satisfaction, HbA1c, and
      subclinical inflammation. RESULTS: Two hundred fourteen participants (mean age
      43.3 +/- 13.3 years, female sex 56.5%, type 2 diabetes 34.1%, mean diabetes
      duration 14.2 +/- 10.5 years, HbA1c 8.9 +/- 1.8%, BMI 28.7 +/- 71 kg/m(2)) were
      randomized. The 12-month follow-up revealed a significantly stronger reduction of
      depressive symptoms (Center for Epidemiologic Studies Depression Scale score) in
      the DIAMOS group compared with the CG (Delta3.9 [95% CI 0.6-7.3], P = 0.021). Of
      the secondary variables, the Patient Health Questionnaire-9 (Delta1.7 [95% CI 0.2
      3.2], P = 0.023), Problem Areas in Diabetes scale (Delta8.2 [95% CI 3.1-13.3], P
      = 0.002), and Diabetes Distress Scale scores (Delta0.3 [95% CI 0.1-0.5], P =
      0.012) displayed significant treatment effects. Moreover, the risk of incident
      major depression in the DIAMOS group was significantly reduced (odds ratio 0.63
      [95% CI 0.42-0.96], P = 0.028). Inflammatory variables were not substantially
      affected. CONCLUSIONS: DIAMOS is more effective in lowering depressive symptoms
      and diabetes-related distress in diabetic patients with subclinical depression.
      DIAMOS also has a preventive effect with respect to the incidence of major
      depression.

PMID- 25605813
TI  - Impact on creatinine renal clearance by the interplay of multiple renal
      transporters: a case study with INCB039110.
AB  - Serum creatinine is commonly used as a marker of renal function, but increases in
      serum creatinine might not represent changes in glomerular filtration rate (GFR).
      INCB039110 (2-(3-(4-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3
      fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3
      yl)acetonitrile) is an inhibitor of the Janus kinases (JAKs) with selectivity for
      JAK1. In a phase 1 study, a modest and reversible increase in serum creatinine
      was observed after treatment with INCB039110. However, a dedicated renal function
      study with INCB039110, assessed by iohexol plasma clearance, conducted in healthy
      volunteers indicated no change in GFR. In vitro studies were therefore conducted
      to investigate the interaction of INCB039110 with five transporters that are
      likely involved in the renal clearance of creatinine. Cell systems expressing
      individual or multiple transporters were used, including a novel quintuple
      transporter model OAT2/OCT2/OCT3/MATE1/MATE2-K. INCB039110 potently inhibited
      OCT2-mediated uptake of creatinine as well as MATE1-/MATE2-K-mediated efflux of
      creatinine. Given the interactions of INCB039110 with multiple transporters
      affecting creatinine uptake and efflux, an integrated system expressing all five
      transporters was sought; in that system, INCB039110 caused a dose-dependent
      decrease in transcellular transport of creatinine with weaker net inhibition
      compared with the effects on individual transporters. In summary, a molecular
      mechanism for the increase in serum creatinine by INCB039110 has been
      established. These studies also underline the limitations of using serum
      creatinine as a marker of renal function. 

PMID- 25605814
TI  - Weight loss >=10% is required by the severely obese to achieve minimal clinically
      important differences in health-related quality of life.

PMID- 25605815
TI  - Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in
      diagnoses of infiltrative glioma.

PMID- 25605816
TI  - The epidemiology of glioma in adults: a "state of the science" review.

PMID- 25605817
TI  - Medulloblastoma subgroup-specific outcomes in irradiated children: who are the
      true high-risk patients?
AB  - BACKGROUND: The advent of integrated genomics has fundamentally changed our
      understanding of medulloblastoma. Although survival differences exist among the 4
      principal subgroups, this has yet to be elucidated in a North American cohort of
      irradiated patients. METHODS: Ninety-two consecutive patients between the ages of
      3 and 17 treated with surgery, craniospinal irradiation, and chemotherapy were
      identified at the Hospital for Sick Children. Molecular subgrouping was performed
      using nanoString. RESULTS: Two treatment periods were identified: prior to 2006
      as per the protocols of the Children's Oncology Group, and after 2006 per the St
      Jude Medulloblastoma 03 protocol. Five-year progression-free survival (PFS) over
      the entire cohort was 0.801 (95% CI: 0.692-0.875) with no significant difference
      between treatment protocols. Strikingly, we found that Group 4 patients had
      excellent 5-year PFS of 0.959 (95% CI: 0.744-0.994) for average risk and 0.887
      (95% CI: 0.727-0.956) across all Group 4 patients. Group 3 patients had 5-year
      PFS of 0.733 (95% CI: 0.436-0.891). Sonic hedgehog patients did poorly across
      both treatment protocols, with 5-year PFS of 0.613 (95% CI: 0.333-0.804), likely
      owing to a high proportion of TP53 mutated patients in this age group.
      CONCLUSIONS: In a cohort of irradiated patients over 3 years of age, PFS for
      Group 4 patients was significantly improved compared with initial reports. The
      impact of subgroup affiliation in these children needs to be assessed in large
      prospectively treated cooperative protocols to determine if more than just WNT
      patients can be safely selected for de-escalation of therapy.

PMID- 25605818
TI  - In vitro screen of a small molecule inhibitor drug library identifies multiple
      compounds that synergize with oncolytic myxoma virus against human brain tumor
      initiating cells.
AB  - BACKGROUND: Brain tumor-initiating cells (BTICs) are stem-like cells hypothesized
      to form a disease reservoir that mediates tumor recurrence in high-grade gliomas.
      Oncolytic virotherapy uses replication-competent viruses to target and kill
      malignant cells and has been evaluated in clinic for glioma therapy with limited
      results. Myxoma virus (MyxV) is a safe and highly effective oncolytic virus (OV)
      in conventional glioma models but, as seen with other OVs, is only modestly
      effective for patient-derived BTICs. The objective of this study was to determine
      whether MyxV treatment against human BTICs could be improved by combining
      chemotherapeutics and virotherapy. METHODS: A 73-compound library of drug
      candidates in clinical use or preclinical development was screened to identify
      compounds that sensitize human BTICs to MyxV treatment in vitro, and synergy was
      evaluated mathematically in lead compounds using Chou-Talalay analyses. The
      effects of combination therapy on viral gene expression and viral replication
      were also assessed. RESULTS: Eleven compounds that enhance MyxV efficacy were
      identified, and 6 were shown to synergize with the virus using Chou-Talalay
      analyses. Four of the synergistic compounds were shown to significantly increase
      viral gene expression, indicating a potential mechanism for synergy. Three highly
      synergistic compounds (axitinib, a VEGFR inhibitor; rofecoxib, a cyclooxygenase-2
      inhibitor; and pemetrexed, a folate anti-metabolite) belong to classes of
      compounds that have not been previously shown to synergize with oncolytic viruses
      in vitro. CONCLUSIONS: This study has identified multiple novel drug candidates
      that synergistically improve MyxV efficacy in a preclinical BTIC glioma model.

PMID- 25605819
TI  - Phase II study of PX-866 in recurrent glioblastoma.
AB  - BACKGROUND: Glioblastoma (GBM) is the most aggressive malignancy of the central
      nervous system in adults. Increased activity of the phosphatidylinositol-3-OH
      kinase (PI3K) signal transduction pathway is common. We performed a phase II
      study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM.
      METHODS: Patients with histologically confirmed GBM at first recurrence were
      given oral PX-866 at a dose of 8 mg daily. An MRI and clinical exam were done
      every 8 weeks. Tissue was analyzed for potential predictive markers. RESULTS:
      Thirty-three participants (12 female) were enrolled. Median age was 56 years
      (range 35-78y). Eastern Cooperative Oncology Group performance status was 0-1 in
      29 participants and 2 in the remainder. Median number of cycles was 1 (range 1
      8). All participants have discontinued therapy: 27 for disease progression and 6
      for toxicity (5 liver enzymes and 1 allergic reaction). Four participants had
      treatment-related serious adverse events (1 liver enzyme, 1 diarrhea, 2 venous
      thromboembolism). Other adverse effects included fatigue, diarrhea, nausea,
      vomiting, and lymphopenia. Twenty-four participants had a response of progression
      (73%), 1 had partial response (3%, and 8 (24%) had stable disease (median, 6.3
      months; range, 3.1-16.8 months). Median 6-month progression-free survival was
      17%. None of the associations between stable disease and PTEN, PIK3CA, PIK3R1, or
      EGFRvIII status were statistically significant. CONCLUSIONS: PX-866 was
      relatively well tolerated. Overall response rate was low, and the study did not
      meet its primary endpoint; however, 21% of participants obtained durable stable
      disease. This study also failed to identify a statistically significant
      association between clinical outcome and relevant biomarkers in patients with
      available tissue.

PMID- 25605820
TI  - Peritoneal dialysis: older patients report better quality of life than younger.

PMID- 25605821
TI  - eComment. Allogeneic red blood cell transfusion: at the turn of sacred and
      scientific eras.

PMID- 25605822
TI  - eComment. Pulmonary metastasectomy of colorectal carcinoma in patients with intra
      thoracic lymph node involvement: a step too far?

PMID- 25605823
TI  - eComment. Does resected lymph-node number influence survival in non-small cell
      lung cancer?

PMID- 25605824
TI  - eComment. Avoiding pressure competition between negative pressure wound therapy
      for poststernotomy mediastinitis and chest drains.

PMID- 25605825
TI  - eComment. Evidence-based selection of conduits in coronary artery bypass
      grafting.

PMID- 25605826
TI  - eComment. Combined surgical strategies for anomalous connection of coronary
      artery to pulmonary artery in adults.

PMID- 25605827
TI  - The prognostic impact of lymph-node dissection on lobectomy for pulmonary
      metastasis.
AB  - OBJECTIVES: The prevalence and characteristics of lymph-node metastasis have not
      been thoroughly investigated in patients with pulmonary metastases from various
      primary neoplasms. The necessity of performing lymph-node dissection with
      pulmonary metastasectomy is unknown. METHODS: We retrospectively reviewed the
      database of the Metastatic Lung Tumor Study Group of Japan. Between November 1980
      and June 2013, 4363 patients underwent resection of pulmonary metastases. After
      selecting for patients who underwent lobectomy, 683 patients (16%) were analysed.
      The presence of lymph-node metastasis, outcomes and prognoses were investigated.
      RESULTS: The primary tumour site was colorectal in 350 patients, head and neck in
      73 patients, kidney in 41 patients, uterus in 41 patients and bone/soft tissue in
      31 patients. The overall 5-year survival rate after pulmonary metastasectomy was
      50.1%, and the 10-year survival rate was 36.4%. Lymph-node metastasis was more
      frequently found in uterine (27%) and head and neck cancers (29%). Five-year
      survival rates were 53.8% in patients without lymph-node metastasis, 39.4% in
      patients with hilar lymph-node metastasis and 30.8% in patients with mediastinal
      lymph-node metastasis. The extent of lymph-node dissection was not related to
      survival. Univariate analysis revealed that tumour size, the presence of lymph
      node metastasis, the presence of multiple lesions, a disease-free interval of 24
      months or less and incomplete resection were significant predictors of poor
      prognosis. Multivariate analysis confirmed these prognostic factors. CONCLUSIONS:
      Retrospective analysis of lobectomy for pulmonary metastasis demonstrated that
      lymph-node metastasis is a significant prognostic factor predicting poor outcome.
      Lymph-node sampling or dissection is therefore warranted to predict patient
      prognosis.

PMID- 25605828
TI  - Electronic versus traditional chest tube drainage following lobectomy: a
      randomized trial.
AB  - OBJECTIVES: Electronic drainage systems have shown superiority compared with
      traditional (water seal) drainage systems following lung resections, but the
      number of studies is limited. As part of a medico-technical evaluation, before
      change of practice to electronic drainage systems for routine thoracic surgery,
      we conducted a randomized controlled trial (RCT) investigating chest tube
      duration and length of hospitalization. METHODS: Patients undergoing lobectomy
      were included in a prospective open label RCT. A strict algorithm was designed
      for early chest tube removal, and this decision was delegated to staff nurses.
      Data were analysed by Cox proportional hazard regression model adjusting for lung
      function, gender, age, BMI, video-assisted thoracic surgery (VATS) or open
      surgery and presence of incomplete fissure or pleural adhesions. Time was
      distinguished as possible (optimal) and actual time for chest tube removal, as
      well as length of hospitalization. RESULTS: A total of 105 patients were
      randomized. We found no significant difference between the electronic group and
      traditional group in optimal chest tube duration (HR = 0.83; 95% CI: 0.55-1.25; P
      = 0.367), actual chest tube duration (HR = 0.84; 95% CI: 0.55-1.26; P = 0.397) or
      length of hospital stay (HR = 0.91; 95% CI: 0.59-1.39; P = 0.651). No chest tubes
      had to be reinserted. Presence of pleural adhesions or an incomplete fissure was
      a significant predictor of chest tube duration (HR = 1.72; 95% CI: 1.15-2.77; P =
      0.014). CONCLUSIONS: Electronic drainage systems did not reduce chest tube
      duration or length of hospitalization significantly compared with traditional
      water seal drainage when a strict algorithm for chest tube removal was used. This
      algorithm allowed delegation of chest tube removal to staff nurses, and in some
      patients chest tubes could be removed safely on the day of surgery.

PMID- 25605829
TI  - Is surgery in acute aortic dissection type A still contraindicated in the
      presence of preoperative neurological symptoms?
AB  - OBJECTIVES: Severe neurological deficit (ND) due to acute aortic dissection type
      A (AADA) was considered a contraindication for surgery because of poor prognosis.
      Recently, more aggressive indication for surgery despite neurological symptoms
      has shown acceptable postoperative clinical results. The aim of this study was to
      evaluate early and mid-term outcomes of patients with AADA presenting with acute
      ND. METHODS: Data from 53 patients with new-onset ND who received surgical repair
      for AADA between 2005 and 2012 at our institution were retrospectively reviewed.
      ND was defined as focal motor or sensory deficit, hemiplegia, paraplegia,
      convulsions or coma. Neurological symptoms were evaluated preoperatively using
      the Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS), and at discharge as
      well as 3-6 months postoperatively using the mRS and National Institutes of
      Health Stroke Scale. Involvement of carotid arteries was assessed in the pre- and
      postoperative computed tomography. Logistic regression analysis was performed to
      detect predictive factors for recovery of ND. RESULTS: Of the 53 patients, 29
      (54.7%) showed complete recovery from focal ND at follow-up. Neurological
      symptoms persisted in 24 (45.3%) patients, of which 8 (33%) died without
      neurological assessment at follow-up. Between the two groups (patients with
      recovery and those with persisting ND), there was no significant difference
      regarding the duration of hypothermic circulatory arrest (28 +/- 14 vs 36 +/- 20
      min) or severely reduced consciousness (GCS <8). Multivariate analysis showed
      significant differences for the preoperative mRS between the two groups (P <
      0.007). A high preoperative mRS was associated with persistence of neurological
      symptoms (P < 0.02). Cardiovascular risk factors, age or involvement of supra
      aortic branches were not predictive for persistence of ND. CONCLUSION: More than
      half of our patients recovered completely from ND due to AADA after surgery.
      Severity of clinical symptoms had a predictive value. Patients suffering from
      AADA and presenting with ND before surgery should not be excluded from emergency
      surgery.

PMID- 25605830
TI  - Repair of post-infarction left ventricular free wall rupture using an
      extracellular matrix patch.
AB  - Several techniques for surgical treatment of acute or subacute left ventricular
      free wall rupture (LVFWR) have been described using a sutured or sutureless patch
      with different currently available materials. We present a case report of a 50
      year-old male with acute LVFWR, who was treated with a simple surgical technique
      using an 'off-pump' epicardially sutured LV patch consisting of an acellular
      xenogeneic extracellular matrix (ECM). ECM patches are structurally more surgeon
      friendly and have shown to be bioactive, and capable of activating remodelling
      and even tissue regeneration. Compared with conventional pericardial patches, the
      advantage of this material is excellent pliability and very easy stitching owing
      to the thin composition of the material. In addition, and most importantly, in
      case of complex structural reconstructions, the patch is highly tear-proof. 

PMID- 25605831
TI  - Outcome of mechanical cardiac support in children using more than one modality as
      a bridge to heart transplantation.
AB  - OBJECTIVES: Mechanical cardiac support (MCS) can successfully be applied as a
      bridging strategy for heart transplantation (OHTx) in children with life
      threatening heart failure. Emergent use of MCS is often required before
      establishing the likelihood of OHTx. This can require bridge-to-bridge strategies
      to increase survival on the waiting list. We compared the outcome of children
      with heart failure who underwent single MCS with those who required multiple MCS
      as a bridge to OHTx. METHODS: A retrospective study of patients aged less than 16
      years was conducted. From March 1998 to October 2005, we used either a veno
      arterial extracorporeal membrane oxygenator (VA-ECMO), or the Medos(r) para
      corporeal ventricular assist device (VAD). From November 2005 onwards, the Berlin
      Heart EXCOR(r) (BHE) device was implanted in the majority of cases. Several
      combinations of bridge-to-bridge strategies have been used: VA-ECMO and then
      conversion to BHE; BHE and then conversion to VA-ECMO; left VAD and then upgraded
      to biventricular support (BIVAD); conversion from pulsatile to continuous-flow
      pumps. RESULTS: A total of 92 patients received MCS with the intent to bridge to
      OHTx, including 21 (23%) supported with more than one modality. The mean age and
      weight at support was similar in both groups, but multimodality MCS was used more
      often in infancy (P = 0.008) and in children less than 10 kg in weight (P =
      0.02). The mean duration of support was longer in the multiple MCS group: 40 +/-
      48 vs 84 +/- 43 days (P = 0.0003). Usage of multimodality MCS in dilated
      cardiomyopathy (19%) and in other diagnoses (29%) was comparable. Incidence of
      major morbidity (haematological sequelae, cerebrovascular events and sepsis) was
      similar in both groups. Survival to OHTx/explantation of the device (recovery)
      and survival to discharge did not differ between single MCS and multiple MCS
      groups (78 vs 81% and 72 vs 76%, respectively). CONCLUSION: Bridge to OHTx with
      multiple MCS does not seem to influence the outcome in our population. Infancy
      and body weight less than 10 kg do not tend to produce higher mortality in the
      multiple MCS group. However, children receiving more than one modality are
      supported for longer durations.

PMID- 25605832
TI  - States as the laboratory for democracy: is anybody paying attention, and does
      anybody care?

PMID- 25605833
TI  - Are immune signatures a worthwhile tool for decision making in early-stage human
      epidermal growth factor receptor 2-positive breast cancer?

PMID- 25605834
TI  - Statins do not protect against cancer: quite the opposite.

PMID- 25605836
TI  - Reply to D.C. Sokal et al.

PMID- 25605835
TI  - Role of magnetic resonance imaging in the management of patients with multiple
      myeloma: a consensus statement.
AB  - PURPOSE: The aim of International Myeloma Working Group was to develop practical
      recommendations for the use of magnetic resonance imaging (MRI) in multiple
      myeloma (MM). METHODS: An interdisciplinary panel of clinical experts on MM and
      myeloma bone disease developed recommendations for the value of MRI based on data
      published through March 2014. RECOMMENDATIONS: MRI has high sensitivity for the
      early detection of marrow infiltration by myeloma cells compared with other
      radiographic methods. Thus, MRI detects bone involvement in patients with myeloma
      much earlier than the myeloma-related bone destruction, with no radiation
      exposure. It is the gold standard for the imaging of axial skeleton, for the
      evaluation of painful lesions, and for distinguishing benign versus malignant
      osteoporotic vertebral fractures. MRI has the ability to detect spinal cord or
      nerve compression and presence of soft tissue masses, and it is recommended for
      the workup of solitary bone plasmacytoma. Regarding smoldering or asymptomatic
      myeloma, all patients should undergo whole-body MRI (WB-MRI; or spine and pelvic
      MRI if WB-MRI is not available), and if they have > one focal lesion of a
      diameter > 5 mm, they should be considered to have symptomatic disease that
      requires therapy. In cases of equivocal small lesions, a second MRI should be
      performed after 3 to 6 months, and if there is progression on MRI, the patient
      should be treated as having symptomatic myeloma. MRI at diagnosis of symptomatic
      patients and after treatment (mainly after autologous stem-cell transplantation)
      provides prognostic information; however, to date, this does not change treatment
      selection.

PMID- 25605837
TI  - KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence.
AB  - PURPOSE: Mutated KIT and platelet-derived growth factor alpha gene (PDGFRA) drive
      GI stromal tumor (GIST) oncogenesis, but the clinical significance of their
      single mutations is known incompletely. PATIENTS AND METHODS: We identified 11
      population-based series of patients with GIST through a literature search and
      pooled individual data from 3,067 patients treated with macroscopically complete
      tumor excision. Mutation analysis was done from 1,505 tumors. We analyzed
      associations between KIT and PDGFRA mutations and recurrence-free survival (RFS)
      in the subsets in which patients were treated with surgery alone. RESULTS: We
      identified 301 different single mutations in KIT and 33 in PDGFRA. Patients with
      PDGFRA mutations had more favorable RFS than those with KIT mutations (hazard
      ratio, 0.34; P = .004). Only one of the 35 GISTs with KIT exon 11 duplication
      mutations recurred. Patients with deletions of only one codon of KIT exon 11 had
      better RFS than those with another deletion type, and some KIT exon 11
      substitution mutations (Trp557Arg, Val559Ala, and Leu576Pro) were also associated
      with favorable RFS. Patients with an identical mutation had greatly variable
      outcomes depending on the standard prognostic factors, notably, mitotic count.
      Commonly used risk stratification schemes tended to overestimate the risk for
      recurrence in subgroups with prognostically favorable mutations. CONCLUSION:
      GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for
      recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11
      duplication mutation or deletion of one codon have favorable RFS with surgery
      alone and are usually not candidates for adjuvant therapy.

PMID- 25605839
TI  - Coexistence of TERT promoter and BRAF mutations in papillary thyroid carcinoma:
      added value in patient prognosis?

PMID- 25605838
TI  - CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus
      Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human
      Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.
AB  - PURPOSE: CEREBEL compared the incidence of CNS metastases as first site of
      relapse in patients with human epidermal growth factor receptor 2-positive
      metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab
      capecitabine. PATIENTS AND METHODS: Patients without baseline CNS metastases were
      randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per
      day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or
      trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an
      infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1
      to 14 every 21 days). The primary end point was incidence of CNS metastases as
      first site of relapse. Secondary end points included progression-free survival
      (PFS) and overall survival (OS). RESULTS: The study was terminated early with 540
      enrolled patients (271 received lapatinib-capecitabine, and 269 received
      trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse
      was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250
      patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2%
      to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus
      lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR
      for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13%
      (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib
      capecitabine and trastuzumab-capecitabine arms, respectively. CONCLUSION: CEREBEL
      is inconclusive for the primary end point, and no difference was detected between
      lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS
      metastases. A better outcome was observed with trastuzumab-capecitabine in the
      overall population. However, lapatinib-capecitabine efficacy may have been
      affected by previous exposure to a trastuzumab regimen and/or when treatment was
      given as first- or second-line therapy in the metastatic setting.

PMID- 25605840
TI  - Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving
      immunotherapy and its association with survival: a systematic review and meta
      analysis.
AB  - PURPOSE: Vitiligo-like depigmentation in patients with melanoma may be associated
      with more favorable clinical outcome. We conducted a systematic review of
      patients with stage III to IV melanoma treated with immunotherapy to determine
      the cumulative incidence of vitiligo-like depigmentation and the prognostic value
      of vitiligo development on survival. METHODS: We systemically searched and
      selected all studies on melanoma immunotherapy that reported on autoimmune
      toxicity and/or vitiligo between 1995 and 2013. Methodologic quality of each
      study was appraised using adapted criteria for systematic reviews in prognostic
      studies. Random-effect models were used to calculate summary estimates of the
      cumulative incidence of vitiligo-like depigmentation across studies. The
      prognostic value of vitiligo-like depigmentation on survival outcome was assessed
      using random-effects Cox regression survival analyses. RESULTS: One hundred
      thirty-seven studies were identified comprising 139 treatment arms (11 general
      immune stimulation, 84 vaccine, 28 antibody-based, and 16 adoptive transfer)
      including a total of 5,737 patients. The overall cumulative incidence of vitiligo
      was 3.4% (95% CI, 2.5% to 4.5%). In 27 studies reporting individual patient data,
      vitiligo development was significantly associated with both progression-free
      survival (hazard ratio [HR], 0.51; 95% CI, 0.32 to 0.82; P < .005) and overall
      survival (HR, 0.25; 95% CI, 0.10 to 0.61; P < .003), indicating that these
      patients have two to four times less risk of disease progression and death,
      respectively, compared with patients without vitiligo development. CONCLUSION:
      Although vitiligo occurs only in a low percentage of patients with melanoma
      treated with immunotherapy, our findings suggest clear survival benefit in these
      patients. Awareness of vitiligo induction in patients with melanoma is important
      as an indicator of robust antimelanoma immunity and associated improved survival.

PMID- 25605841
TI  - Anxiety and health-related quality of life among patients with low-tumor burden
      non-Hodgkin lymphoma randomly assigned to two different rituximab dosing
      regimens: results from ECOG trial E4402 (RESORT).
AB  - PURPOSE: The purpose of this study was to compare illness-related anxiety among
      participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT)
      randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment
      (RR). A secondary objective was to examine whether the superiority of MR versus
      RR on anxiety depended on illness-related coping style. PATIENTS AND METHODS:
      Patients (N = 253) completed patient-reported outcome (PRO) measures at random
      assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after
      random assignment; and at rituximab failure. PRO measures assessed illness
      related anxiety and coping style, and secondary end points including general
      anxiety, worry and interference with emotional well-being, depression, and health
      related quality of life (HRQoL). Patients were classified as using an active or
      avoidant illness-related coping style. Independent sample t tests and linear
      mixed-effects models were used to identify treatment arm differences on PRO end
      points and differences based on coping style. RESULTS: Illness-related anxiety
      was comparable between treatment arms at all time points (P > .05), regardless of
      coping style (active or avoidant). Illness-related anxiety and general anxiety
      significantly decreased over time on both arms. HRQoL scores were relatively
      stable and did not change significantly from baseline for both arms. An avoidant
      coping style was associated with significantly higher anxiety (18% and 13%
      exceeded clinical cutoff points at baseline and 6 months, respectively) and
      poorer HRQoL compared with an active coping style (P < .001), regardless of
      treatment arm assignment. CONCLUSION: Surveillance until RR at progression was
      not associated with increased anxiety compared with MR, regardless of coping
      style. Avoidant coping was associated with higher anxiety and poorer HRQoL.

PMID- 25605842
TI  - Therapeutic landscape of carfilzomib and other modulators of the ubiquitin
      proteasome pathway.

PMID- 25605843
TI  - Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS
      mutations in colorectal cancer.
AB  - PURPOSE: The phase III CRYSTAL study demonstrated that addition of cetuximab to
      fluorouracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall
      survival, progression-free survival, and objective response in the first-line
      treatment of patients with KRAS codon 12/13 (exon 2) wild-type metastatic
      colorectal cancer (mCRC). Outcome was reassessed in subgroups defined by extended
      RAS mutation testing. PATIENTS AND METHODS: Existing DNA samples from KRAS exon 2
      wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS
      mutations in four additional KRAS codons (exons 3 and 4) and six NRAS codons
      (exons 2, 3, and 4) using beads, emulsion, amplification, and magnetics
      technology. No tissue microdissection was performed. A >= 5% mutant allele cutoff
      was used to call mutations. RESULTS: Mutation status was evaluable in 430 (64.6%)
      of 666 patients with KRAS exon 2 wild-type tumors. Other RAS mutations were
      detected in 63 (14.7%) of 430 patients. In those with RAS wild-type tumors, a
      significant benefit across all efficacy end points was associated with the
      addition of cetuximab to FOLFIRI. In patients with other RAS tumor mutations, no
      difference in efficacy outcomes between treatment groups was seen. The safety
      profile in RAS subgroups was similar and in line with expectations. CONCLUSION:
      In the first-line treatment of mCRC, patients with RAS wild-type tumors derived a
      significant benefit from the addition of cetuximab to FOLFIRI; patients with RAS
      tumor mutations did not. Molecular testing of tumors for all activating RAS
      mutations is essential before considering anti-epidermal growth factor receptor
      therapy, thereby allowing the further tailoring of cetuximab administration to
      maximize patient benefit.

PMID- 25605844
TI  - Venous thromboembolism prophylaxis and treatment in patients with cancer:
      american society of clinical oncology clinical practice guideline update 2014.
AB  - PURPOSE: To provide current recommendations about the prophylaxis and treatment
      of venous thromboembolism (VTE) in patients with cancer. METHODS: PubMed and the
      Cochrane Library were searched for randomized controlled trials, systematic
      reviews, meta-analyses, and clinical practice guidelines from November 2012
      through July 2014. An update committee reviewed the identified abstracts.
      RESULTS: Of the 53 publications identified and reviewed, none prompted a change
      in the 2013 recommendations. RECOMMENDATIONS: Most hospitalized patients with
      active cancer require thromboprophylaxis throughout hospitalization. Routine
      thromboprophylaxis is not recommended for patients with cancer in the outpatient
      setting. It may be considered for selected high-risk patients. Patients with
      multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or
      dexamethasone should receive prophylaxis with either low-molecular weight heparin
      (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive
      prophylaxis starting before surgery and continuing for at least 7 to 10 days.
      Extending prophylaxis up to 4 weeks should be considered in those undergoing
      major abdominal or pelvic surgery with high-risk features. LMWH is recommended
      for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary
      embolism as well as for long-term secondary prophylaxis (at least 6 months). Use
      of novel oral anticoagulants is not currently recommended for patients with
      malignancy and VTE because of limited data in patients with cancer.
      Anticoagulation should not be used to extend survival of patients with cancer in
      the absence of other indications. Patients with cancer should be periodically
      assessed for VTE risk. Oncology professionals should educate patients about the
      signs and symptoms of VTE.

PMID- 25605846
TI  - Mortality in colorectal cancer and use of statins.

PMID- 25605847
TI  - Advanced skeletal imaging redefines the management of plasma cell disorders.

PMID- 25605845
TI  - Immune Checkpoint Blockade in Cancer Therapy.
AB  - Immunologic checkpoint blockade with antibodies that target cytotoxic T
      lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1
      pathway (PD-1/PD-L1) have demonstrated promise in a variety of malignancies.
      Ipilimumab (CTLA-4) and pembrolizumab (PD-1) are approved by the US Food and Drug
      Administration for the treatment of advanced melanoma, and additional regulatory
      approvals are expected across the oncologic spectrum for a variety of other
      agents that target these pathways. Treatment with both CTLA-4 and PD-1/PD-L1
      blockade is associated with a unique pattern of adverse events called immune
      related adverse events, and occasionally, unusual kinetics of tumor response are
      seen. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade are being
      investigated to determine whether they enhance the efficacy of either approach
      alone. Principles learned during the development of CTLA-4 and PD-1/PD-L1
      approaches will likely be used as new immunologic checkpoint blocking antibodies
      begin clinical investigation. 

PMID- 25605848
TI  - Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in
      patients with disseminated germ cell tumors treated with chemotherapy.
AB  - PURPOSE: Cisplatin-based chemotherapy, a mainstay of treatment for disseminated
      germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many
      patients with disseminated GCTs have large retroperitoneal lymph node (RPLN)
      metastases that may cause venous stasis and increase the risk of VTE development.
      We hypothesized that there was an association between large RPLN and chemotherapy
      associated VTE risk. PATIENTS AND METHODS: The training cohort was composed of
      patients with disseminated GCT receiving first-line chemotherapy at Princess
      Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was
      defined as more than 5 cm in maximal axial diameter. The predictive and
      discriminatory accuracies of a model using large RPLN in predicting VTE were
      compared with high-risk Khorana score (>= 3) using logistic regression and area
      under receiver operator characteristic curves (AUROCs). The model was externally
      validated in a cohort of patients treated at the London Health Sciences Centre.
      RESULTS: The training cohort comprised 216 patients, 21 (10%) of whom developed
      VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR],
      5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor
      risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR,
      4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk
      Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory
      accuracy of large RPLN over high-risk Khorana score was validated in the London
      cohort (AUROC, 0.61 v 0.57, respectively). CONCLUSION: Large RPLN is associated
      with VTE in patients with disseminated GCT and provides higher discriminatory
      accuracy than high-risk Khorana score. Results should be validated in larger,
      prospective studies. Prophylactic anticoagulation may be considered in high-risk
      patients.

PMID- 25605849
TI  - Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as
      monotherapy and in combination with gemcitabine in patients with advanced solid
      tumors.
AB  - PURPOSE: We determined the safety, pharmacokinetics, pharmacodynamics, and
      recommended phase II dose of MK-8776 (SCH 900776), a potent, selective checkpoint
      kinase 1 (Chk1) inhibitor, as monotherapy and in combination with gemcitabine in
      a first-in-human phase I clinical trial in patients with advanced solid tumor
      malignancies. PATIENTS AND METHODS: Forty-three patients were treated by
      intravenous infusion with MK-8776 at seven dose levels ranging from 10 to 150
      mg/m(2) as monotherapy and then in combination with gemcitabine 800 mg/m(2) (part
      A, n = 26) or gemcitabine 1,000 mg/m(2) (part B, n = 17). Forty percent of
      patients had three or more prior treatment regimens, and one third of patients
      had previously received gemcitabine. RESULTS: As monotherapy, MK-8776 was well
      tolerated, with QTc prolongation (19%), nausea (16%), fatigue (14%), and
      constipation (14%) as the most frequent adverse effects. Combination therapy
      demonstrated a higher frequency of adverse effects, predominantly fatigue (63%),
      nausea (44%), decreased appetite (37%), thrombocytopenia (32%), and neutropenia
      (24%), as well as dose-related, transient QTc prolongation (17%). The median
      number of doses of MK-8776 administered was five doses, with relative dose
      intensity of 0.96. Bioactivity was assessed by gamma-H2AX ex vivo assay. Of 30
      patients evaluable for response, two showed partial response, and 13 exhibited
      stable disease. CONCLUSION: MK-8776 was well tolerated as monotherapy and in
      combination with gemcitabine. Early evidence of clinical efficacy was observed.
      The recommended phase II dose is MK-8776 200 mg plus gemcitabine 1,000 mg/m(2) on
      days 1 and 8 of a 21-day cycle.

PMID- 25605850
TI  - Prostate cancer and vasectomy: deja vu!

PMID- 25605851
TI  - What we really talk about when we talk about food.

PMID- 25605852
TI  - Precision immunology: the promise of immunotherapy for the treatment of cancer.

PMID- 25605854
TI  - Reply to U. Ravnskov et al, D. Tural et al, and M.A.N. Sendur et al.

PMID- 25605853
TI  - Utility of early screening magnetic resonance imaging for extensive hip
      osteonecrosis in pediatric patients treated with glucocorticoids.
AB  - PURPOSE: Hip osteonecrosis frequently complicates treatment with glucocorticoids.
      When extensive (affecting >= 30% of the epiphyseal surface), 80% of joints
      collapse within 2 years, so interventions are needed to prevent this outcome.
      PATIENTS AND METHODS: This prospective cohort magnetic resonance imaging (MRI)
      screening study included all consecutive children treated for acute lymphoblastic
      leukemia on a single protocol. Hip MRI was performed at 6.5 and 9 months from
      diagnosis (early screening) and at completion of chemotherapy (final evaluation)
      to determine whether screening could identify extensive hip osteonecrosis before
      symptom development. RESULTS: Of 498 patients, 462 underwent screening MRI.
      Extensive asymptomatic osteonecrosis was identified by early screening in 26
      patients (41 hips); another four patients (seven hips) were detected after the
      screening period, such that screening sensitivity was 84.1% and specificity was
      99.4%. The number of joints screened to detect one lesion was 20.1 joints for all
      patients, 4.4 joints for patients older than 10 years, and 198 joints for
      patients <= 10 years old (P < .001). Of the 40 extensive lesions in patients
      older than 10 years, 19 required total hip arthroplasty and none improved. Of
      eight extensive lesions in younger patients, none required arthroplasty and four
      improved. CONCLUSION: In patients age 10 years old or younger who require
      prolonged glucocorticoid therapy, screening for extensive hip osteonecrosis is
      unnecessary because their risk is low and lesions tend to heal. In children older
      than 10 years, early screening successfully identifies extensive asymptomatic
      lesions in patients who would be eligible for studies of interventions to prevent
      or delay joint collapse.

PMID- 25605855
TI  - Do statins really improve colorectal cancer-specific mortality?

PMID- 25605857
TI  - Monitoring of minimal residual disease after allogeneic stem-cell transplantation
      in relapsed childhood acute lymphoblastic leukemia allows for the identification
      of impending relapse: results of the ALL-BFM-SCT 2003 trial.
AB  - PURPOSE: To elucidate the impact of minimal residual disease (MRD) after
      allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt
      Munster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective
      clinical trial. PATIENTS AND METHODS: In the ALL-BFM-SCT 2003 trial, MRD was
      assessed in the bone marrow at days +30, +60, +90, +180, and +365 after
      transplantation in 113 patients with relapsed disease. Standardized
      quantification of MRD was performed according to the guidelines of the Euro-MRD
      Group. RESULTS: All patients showed a 3-year probability of event-free survival
      (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related
      mortality were 32% and 12%, respectively. The pEFS was 60% for patients who
      received their transplantations in second complete remission, 50% for patients in
      >= third complete remission, and 0% for patients not in remission (P = .015). At
      all time points, the level of MRD was inversely correlated with event-free
      survival (EFS; P < .004) and positively correlated with the cumulative incidence
      of relapse (P < .01). A multivariable Cox model was fitted for each time point,
      which showed that MRD >= 10(-4) leukemic cells was consistently correlated with
      inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse
      was investigated with time-dependent receiver operating curves at days +30, +60,
      +90, and +180. From day +60 onward, the discriminatory power of MRD detection to
      predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%,
      more than 87%, more than 71%, and more than 61%, respectively. CONCLUSION: MRD
      after transplantation was a reliable marker for predicting impending relapses and
      could thus serve as the basis for pre-emptive therapy.

PMID- 25605858
TI  - When is good enough really good enough? Defining the role of radiation in low
      risk ductal carcinoma in situ.

PMID- 25605856
TI  - RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ
      comparing radiotherapy with observation.
AB  - PURPOSE: The Radiation Therapy Oncology Group 9804 study identified good-risk
      patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found
      frequently in mammographically detected cancers, to test the benefit of
      radiotherapy (RT) after breast-conserving surgery compared with observation.
      PATIENTS AND METHODS: This prospective randomized trial (1998 to 2006) in women
      with mammographically detected low- or intermediate-grade DCIS, measuring less
      than 2.5 cm with margins >= 3 mm, compared RT with observation after surgery. The
      study was designed for 1,790 patients but was closed early because of lower than
      projected accrual. Six hundred thirty-six patients from the United States and
      Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure
      (LF) was the primary end point; LF and contralateral failure were estimated using
      cumulative incidence, and overall and disease-free survival were estimated using
      the Kaplan-Meier method. RESULTS: Median follow-up time was 7.17 years (range,
      0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the
      observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the
      RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio,
      0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in
      30% and 76% of patients in the observation and RT arms, respectively; grade 3 or
      4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT
      toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.
      CONCLUSION: In this good-risk subset of patients with DCIS, with a median follow
      up of 7 years, the LF rate was low with observation but was decreased
      significantly with the addition of RT. Longer follow-up is planned because the
      timeline for LF in this setting seems protracted.

PMID- 25605859
TI  - Reply to M. Melo et al.

PMID- 25605860
TI  - Are all chimeric antigen receptors created equal?

PMID- 25605861
TI  - Genomic analysis reveals that immune function genes are strongly linked to
      clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant
      Trastuzumab Trial.
AB  - PURPOSE: To develop a genomic signature that predicts benefit from trastuzumab in
      human epidermal growth factor receptor 2-positive breast cancer. PATIENTS AND
      METHODS: DASL technology was used to quantify mRNA in samples from 1,282 patients
      enrolled onto the Combination Chemotherapy With or Without Trastuzumab in
      Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831
      [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs),
      adjusted for significant clinicopathologic risk factors, were used to determine
      the association of each gene with relapse-free survival (RFS) for 433 patients
      who received chemotherapy alone (arm A) and 849 patients who received
      chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were
      used to identify key biologic processes linked to RFS. The signature was built by
      using a voting scheme. RESULTS: Network and functional ontology analyses
      suggested that increased RFS was linked to a subset of immune function genes. A
      voting scheme model was used to define immune gene enrichment based on the
      expression of any nine or more of 14 immune function genes at or above the 0.40
      quantile for the population. This model was used to identify immune gene-enriched
      tumors in arm A and arms B and C. Immune gene enrichment was linked to increased
      RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and
      C patients who did not exhibit immune gene enrichment did not benefit from
      trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function
      gene expression as defined by our predictive signature was not associated with
      increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64). CONCLUSION:
      Increased expression of a subset of immune function genes may provide a means of
      predicting benefit from adjuvant trastuzumab.

PMID- 25605862
TI  - Phase III open-label randomized study of eribulin mesylate versus capecitabine in
      patients with locally advanced or metastatic breast cancer previously treated
      with an anthracycline and a taxane.
AB  - PURPOSE: This phase III randomized trial (ClinicalTrials.gov identifier:
      NCT00337103) compared eribulin with capecitabine in patients with locally
      advanced or metastatic breast cancer (MBC). PATIENTS AND METHODS: Women with MBC
      who had received prior anthracycline- and taxane-based therapy were randomly
      assigned to receive eribulin or capecitabine as their first-, second-, or third
      line chemotherapy for advanced/metastatic disease. Stratification factors were
      human epidermal growth factor receptor-2 (HER2) status and geographic region.
      Coprimary end points were overall survival (OS) and progression-free survival
      (PFS). RESULTS: Median OS times for eribulin (n = 554) and capecitabine (n = 548)
      were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to
      1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2
      months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective
      response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health
      status and overall quality-of-life scores over time were similar in the treatment
      arms. Both treatments had manageable safety profiles consistent with their known
      adverse effects; most adverse events were grade 1 or 2. CONCLUSION: In this phase
      III study, eribulin was not shown to be superior to capecitabine with regard to
      OS or PFS.

PMID- 25605863
TI  - Clinical cancer advances 2015: Annual report on progress against cancer from the
      American Society of Clinical Oncology.

PMID- 25605864
TI  - Cigarette smoking and pulmonary tuberculosis in northern California.
AB  - BACKGROUND: A positive association between smoking and increased risk of
      tuberculosis disease is well documented for populations outside the USA. However,
      it is unclear whether smoking increases risk of tuberculosis in the USA, where
      both smoking prevalence and disease rates are much lower than in the countries
      where previous studies have been conducted. METHODS: To explore the tuberculosis
      smoking association in a more generalisable US population-based sample, we
      conducted a nested case-control study among members of Kaiser Permanente Northern
      California (KPNC). We identified all newly diagnosed cases of active pulmonary
      tuberculosis (PTB) disease between 1996 and 2010. Each of the 2380 cases were
      individually matched to two controls by age, gender and race/ethnicity. ORs and
      95% CIs for the association between smoking status and PTB were calculated using
      conditional logistic regression adjusted for all matching factors. RESULTS:
      Increased PTB risk was observed among ever-smokers (OR=1.35; 95% CI 1.19 to
      1.53), as well as current (OR=1.26; 95% CI 1.08 to 1.48) and past (OR=1.43; 95%
      CI 1.23 to 1.67) smokers, compared with never-smokers. Increased intensity and
      duration of smoking were also positively associated with PTB risk. CONCLUSIONS:
      Our findings among a more generalisable US population support the hypothesis that
      smoking increases risk of PTB, underscoring the importance of tobacco cessation
      and prevention programmes in eliminating tuberculosis.

PMID- 25605865
TI  - Job strain and trajectories of change in episodic memory before and after
      retirement: results from the Health and Retirement Study.
AB  - BACKGROUND: We examined indicators of job strain in relation to level and change
      in episodic memory in the years leading up to as well as following retirement.
      METHODS: Our analyses centre on 3779 individuals from the nationally
      representative Health and Retirement Study (baseline age 57.3 years) who reported
      gainful employment in an occupation for 10+ years prior to retirement, and who
      were assessed for episodic memory performance over up to 20 years (median 8 waves
      over 16 years). We used ratings from the Occupational Information Network (O*Net)
      to score occupations for job control and job demands, and to measure job strain
      (job demands/job control). RESULTS: Controlling for sociodemographic
      characteristics, depressive symptoms, and cardiovascular disease, less job
      control and greater job strain were not significantly associated with change in
      episodic memory in the period leading up to retirement, but were associated with
      significantly poorer episodic memory at retirement and an accelerated rate of
      decline in episodic memory following retirement. The results did not vary for men
      and women or by self-employment status. CONCLUSIONS: Job strain expressed mainly
      as low job control is linked to poorer episodic memory at retirement and more
      decline after retirement. Job characteristics appear to have implications for
      cognitive ageing independent of relevant confounds.

PMID- 25605866
TI  - Myeloid-related protein 14 promotes inflammation and injury in meningitis.
AB  - BACKGROUND: Neutrophilic inflammation often persists for days despite effective
      antibiotic treatment and contributes to brain damage in bacterial meningitis. We
      propose here that myeloid-related protein 14 (MRP14), an abundant cytosolic
      protein in myeloid cells, acts as an endogenous danger signal, driving
      inflammation and aggravating tissue injury. METHODS: The release pattern of MRP14
      was analyzed in human and murine cerebrospinal fluid (CSF), as well as in
      isolated neutrophils. Its functional role was assessed in a mouse meningitis
      model, using MRP14-deficient mice. RESULTS: We detected large quantities of MRP14
      in CSF specimens from patients and mice with pneumococcal meningitis.
      Immunohistochemical analyses and a cell-depletion approach indicated neutrophils
      as the major source of MRP14. In a meningitis model, MRP14-deficient mice showed
      a better resolution of inflammation during antibiotic therapy, which was
      accompanied by reduced disease severity. Intrathecal administration of MRP14
      before infection reverted the phenotype of MRP14-deficient mice back to wild
      type. Moreover, intrathecal injection of MRP14 alone was sufficient to induce
      meningitis in a Toll-like receptor 4 (TLR4)-CXCL2-dependent manner. Finally,
      treatment with the MRP14 antagonist paquinimod reduced inflammation and disease
      severity significantly, reaching levels comparable to those achieved after
      genetic depletion of MRP14. CONCLUSIONS: The present study implicates MRP14 as an
      essential propagator of inflammation and potential therapeutic target in
      pneumococcal meningitis.

PMID- 25605867
TI  - Bacteriophage-loaded nanostructured lipid carrier: improved pharmacokinetics
      mediates effective resolution of Klebsiella pneumoniae-induced lobar pneumonia.
AB  - This study examined the therapeutic and prophylactic potential of bacteriophages
      in a mouse model of Klebsiella pneumoniae lobar pneumonia. Phages were
      administered intraperitoneally. Liposome-entrapped phages (LP) were effective in
      treating infection, even when therapy was delayed by 3 days after the induction
      of pneumonia. In contrast, nonliposomal phages provided protection when
      administered 24 hours after infection. Administration of nonliposomal phages 6
      hours prior to intranasal bacterial challenge resulted in complete protection,
      compared with LP, which was effective even when administered 48 hours prior to
      infection. Increased reduction and a greater increment in the levels of
      proinflammatory and antiinflammatory cytokines, respectively, in homogenates of
      lung from LP-treated mice were suggestive of increased efficacy of LP in the
      treatment of pneumonia. This is the first study to assess liposomes as a delivery
      vehicle for phage, and the results confirm the superiority of LP for both
      therapeutic and prophylactic applications. 

PMID- 25605868
TI  - A thermonuclease of Neisseria gonorrhoeae enhances bacterial escape from killing
      by neutrophil extracellular traps.
AB  - Acute gonorrhea is characterized by neutrophilic inflammation that is
      insufficient to clear Neisseria gonorrhoeae. Activated neutrophils release
      extracellular traps (NETs), which are composed of chromatin and decorated with
      antimicrobial proteins. The N. gonorrhoeae NG0969 open reading frame contains a
      gene (nuc) that encodes a putatively secreted thermonuclease (Nuc) that
      contributes to biofilm remodeling. Here, we report that Nuc degrades NETs to help
      N. gonorrhoeae resist killing by neutrophils. Primary human neutrophils released
      NETs after exposure to N. gonorrhoeae, but NET integrity declined over time with
      Nuc-containing bacteria. Recombinant Nuc and conditioned medium from Nuc
      containing N. gonorrhoeae degraded human neutrophil DNA and NETs. NETs were found
      to have antimicrobial activity against N. gonorrhoeae, and Nuc expression
      enhanced N. gonorrhoeae survival in the presence of neutrophils that released
      NETs. We propose that Nuc enables N. gonorrhoeae to escape trapping and killing
      by NETs during symptomatic infection, highlighting Nuc as a multifunctional
      virulence factor for N. gonorrhoeae. 

PMID- 25605870
TI  - Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through
      adaptor ASC phosphorylation and enhanced oligomerization.
AB  - NLRP3 is the most crucial member of the NLR family, as it detects the existence
      of pathogen invasion and self-derived molecules associated with cellular damage.
      Several studies have reported that excessive NLRP3 inflammasome-mediated caspase
      1 activation is a key factor in the development of diseases. Recent studies have
      reported that Syk is involved in pathogen-induced NLRP3 inflammasome activation;
      however, the detailed mechanism linking Syk to NLRP3 inflammasome remains
      unclear. In this study, we showed that Syk mediates NLRP3 stimuli-induced
      processing of procaspase-1 and the consequent activation of caspase-1. Moreover,
      the kinase activity of Syk is required to potentiate caspase-1 activation in a
      reconstituted NLRP3 inflammasome system in HEK293T cells. The adaptor protein ASC
      bridges NLRP3 with the effector protein caspase-1. Herein, we find that Syk can
      associate directly with ASC and NLRP3 by its kinase domain but interact
      indirectly with procaspase-1. Syk can phosphorylate ASC at Y146 and Y187
      residues, and the phosphorylation of both residues is critical to enhance ASC
      oligomerization and the recruitment of procaspase-1. Together, our results reveal
      a new molecular pathway through which Syk promotes NLRP3 inflammasome formation,
      resulting from the phosphorylation of ASC. Thus, the control of Syk activity
      might be effective to modulate NLRP3 inflammasome activation and treat NLRP3
      related immune diseases.

PMID- 25605869
TI  - gammadelta T Cells and dendritic cells in refractory Lyme arthritis.
AB  - Lyme disease is a multisystem infection transmitted by tick vectors with an
      incidence of up to 300,000 individuals/yr in the United States. The primary
      treatments are oral or i.v. antibiotics. Despite treatment, some individuals do
      not recover and have prolonged symptoms affecting multiple organs, including the
      nervous system and connective tissues. Inflammatory arthritis is a common symptom
      associated with Lyme pathology. In the past decades, gammadelta T cells have
      emerged as candidates that contribute to the transition from innate to adaptive
      responses. These cells are also differentially regulated within the synovia of
      patients affected by RLA. Here, we review and discuss potential cellular
      mechanisms involving gammadelta T cells and DCs in RLA. TLR signaling and antigen
      processing and presentation will be the key concepts that we review in aid of
      understanding the impact of gammadelta T cells in RLA. 

PMID- 25605871
TI  - Chronic ethanol feeding increases the severity of Staphylococcus aureus skin
      infections by altering local host defenses.
AB  - Alcoholics are at increased risk of Staphylococcus aureus skin infection and
      serious sequelae, such as bacteremia and death. Despite the association between
      alcoholism and severe S. aureus skin infection, the impact of EtOH on anti-S.
      aureus cutaneous immunity has not been investigated in a model of chronic EtOH
      exposure. To test the hypothesis that EtOH enhances the severity of S. aureus
      skin infection, mice were fed EtOH for >=12 weeks via the Meadows-Cook model of
      alcoholism and inoculated with S. aureus following epidermal abrasion. Evidence
      of exacerbated staphylococcal disease in EtOH-fed mice included: skin lesions
      that were larger and contained more organisms, greater weight loss, and increased
      bacterial dissemination. Infected EtOH-fed mice demonstrated poor maintenance and
      induction of PMN responses in skin and draining LNs, respectively. Additionally,
      altered PMN dynamics in the skin of these mice corresponded with reduced
      production of IL-23 and IL-1beta by CD11b(+) myeloid cells and IL-17 production
      by gammadelta T cells, with the latter defect occurring in the draining LNs as
      well. In addition, IL-17 restoration attenuated S. aureus-induced
      dermatopathology and improved bacterial clearance defects in EtOH-fed mice. Taken
      together, the findings show, in a novel model system, that the EtOH-induced
      increase in S. aureus-related injury/illness corresponds with defects in the IL
      23/IL-17 inflammatory axis and poor PMN accumulation at the site of infection and
      draining LNs. These findings offer new information about the impact of EtOH on
      cutaneous host-defense pathways and provide a potential mechanism explaining why
      alcoholics are predisposed to S. aureus skin infection. 

PMID- 25605872
TI  - Simian immunodeficiency virus infection and immune responses in the pig-tailed
      macaque testis.
AB  - The testis is a site of immune privilege in rodents, and there is evidence that T
      cell responses are also suppressed in the primate testis. Local immunosuppression
      is a potential mechanism for HIV persistence in tissue reservoirs that few
      studies have examined. The response of the pig-tailed macaque testis to SIVmac239
      infection was characterized to test this possibility. Testes were surgically
      removed during early-chronic (10 wk) and late-chronic (24-30 wk) SIV infection in
      4 animals and compared with those from 7 uninfected animals. SIV infection caused
      only minor disruption to the seminiferous epithelium without marked evidence of
      inflammation or consistent changes in total intratesticular leukocyte numbers.
      Infection also led to an increase in the relative proportion of testicular
      effector memory CD8(+) T cell numbers and a corresponding reduction in central
      memory CD4(+) T cells. A decrease in the relative proportion of resident-type
      CD163(+) macrophages and DCs was also observed. SIV-specific CD8(+) T cells were
      detectable in the testis, 10-11 wk after infection by staining with SIV Gag
      specific or Tat-specific MHC-I tetramers. However, testicular CD8(+) T cells from
      the infected animals had suppressed cytokine responses to mitogen activation.
      These results support the possibility that local immunosuppression in the testis
      may be restricting the ability of T cells to respond to SIV or HIV infection.
      Local immunosuppression in the testis may be an underexplored mechanism allowing
      HIV persistence. 

PMID- 25605873
TI  - 12/15-Lipoxygenase metabolites of arachidonic acid activate PPARgamma: a possible
      neuroprotective effect in ischemic brain.
AB  - The enzyme 12/15-lipoxygenase (LOX) oxidizes various free fatty acids, including
      arachidonic acid (AA). In the brain, the principal 12/15-LOX metabolites of AA
      are 12(S)-HETE and 15(S)-HETE. PPARgamma is a nuclear receptor whose activation
      is neuroprotective through its anti-inflammatory properties. In this study, we
      investigate the involvement of 12(S)- and 15(S)-HETE in the regulation of
      PPARgamma following cerebral ischemia and their effects on ischemia-induced
      inflammatory response. We show here the increased expression of 12/15-LOX,
      predominantly in neurons, and elevated production of 12(S)-HETE and 15(S)-HETE in
      ischemic brain. The exogenous 12(S)- and 15(S)-HETE increase PPARgamma protein
      level, nuclear translocation, and DNA-binding activity in ischemic rats,
      suggesting the activation of PPARgamma. This effect was further confirmed by
      showing the increased PPARgamma transcriptional activity in primary cortical
      neurons when incubated with 12(S)- or 15(S)-HETE. Moreover, both 12(S)- and 15(S)
      HETE potently inhibited the induction of nuclear factor-kappaB, inducible NO
      synthase, and cyclooxygenase-2 in ischemic rats, and elicited neuroprotection.
      The reversal of the effects of 12(S)- and 15(S)-HETE on pro-inflammatory factors
      by PPARgamma antagonist GW9662 indicated their actions were mediated via
      PPARgamma. Thus, the induction of 12(S)- and 15(S)-HETE during brain ischemia
      suggests that endogenous signals of neuroprotection may be generated. 

PMID- 25605874
TI  - All members in the sphingomyelin synthase gene family have ceramide
      phosphoethanolamine synthase activity.
AB  - Sphingomyelin synthase-related protein (SMSr) synthesizes the sphingomyelin
      analog ceramide phosphoethanolamine (CPE) in cells. Previous cell studies
      indicated that SMSr is involved in ceramide homeostasis and is crucial for cell
      function. To further examine SMSr function in vivo, we generated Smsr KO mice
      that were fertile and had no obvious phenotypic alterations. Quantitative MS
      analyses of plasma, liver, and macrophages from the KO mice revealed only
      marginal changes in CPE and ceramide as well as other sphingolipid levels.
      Because SMS2 also has CPE synthase activity, we prepared Smsr/Sms2 double KO
      mice. We found that CPE levels were not significantly changed in macrophages,
      suggesting that CPE levels are not exclusively dependent on SMSr and SMS2
      activities. We then measured CPE levels in Sms1 KO mice and found that Sms1
      deficiency also reduced plasma CPE levels. Importantly, we found that expression
      of Sms1 or Sms2 in SF9 insect cells significantly increased not only SM but also
      CPE formation, indicating that SMS1 also has CPE synthase activity. Moreover, we
      measured CPE synthase Km and Vmax for SMS1, SMS2, and SMSr using different NBD
      ceramides. Our study reveals that all mouse SMS family members (SMSr, SMS1, and
      SMS2) have CPE synthase activity. However, neither CPE nor SMSr appears to be a
      critical regulator of ceramide levels in vivo. 

PMID- 25605875
TI  - Oldest known euarchontan tarsals and affinities of Paleocene Purgatorius to
      Primates.
AB  - Earliest Paleocene Purgatorius often is regarded as the geologically oldest
      primate, but it has been known only from fossilized dentitions since it was first
      described half a century ago. The dentition of Purgatorius is more primitive than
      those of all known living and fossil primates, leading some researchers to
      suggest that it lies near the ancestry of all other primates; however, others
      have questioned its affinities to primates or even to placental mammals. Here we
      report the first (to our knowledge) nondental remains (tarsal bones) attributed
      to Purgatorius from the same earliest Paleocene deposits that have yielded
      numerous fossil dentitions of this poorly known mammal. Three independent
      phylogenetic analyses that incorporate new data from these fossils support
      primate affinities of Purgatorius among euarchontan mammals (primates,
      treeshrews, and colugos). Astragali and calcanei attributed to Purgatorius
      indicate a mobile ankle typical of arboreal euarchontan mammals generally and of
      Paleocene and Eocene plesiadapiforms specifically and provide the earliest fossil
      evidence of arboreality in primates and other euarchontan mammals. Postcranial
      specializations for arboreality in the earliest primates likely played a key role
      in the evolutionary success of this mammalian radiation in the Paleocene. 

PMID- 25605876
TI  - Climate, vocal folds, and tonal languages: Connecting the physiological and
      geographic dots.
AB  - We summarize a number of findings in laryngology demonstrating that perturbations
      of phonation, including increased jitter and shimmer, are associated with
      desiccated ambient air. We predict that, given the relative imprecision of vocal
      fold vibration in desiccated versus humid contexts, arid and cold ecologies
      should be less amenable, when contrasted to warm and humid ecologies, to the
      development of languages with phonemic tone, especially complex tone. This
      prediction is supported by data from two large independently coded databases
      representing 3,700+ languages. Languages with complex tonality have generally not
      developed in very cold or otherwise desiccated climates, in accordance with the
      physiologically based predictions. The predicted global geographic-linguistic
      association is shown to operate within continents, within major language
      families, and across language isolates. Our results offer evidence that human
      sound systems are influenced by environmental factors. 

PMID- 25605877
TI  - Functional human antibody CDR fusions as long-acting therapeutic endocrine
      agonists.
AB  - On the basis of the 3D structure of a bovine antibody with a well-folded,
      ultralong complementarity-determining region (CDR), we have developed a versatile
      approach for generating human or humanized antibody agonists with excellent
      pharmacological properties. Using human growth hormone (hGH) and human leptin
      (hLeptin) as model proteins, we have demonstrated that functional human antibody
      CDR fusions can be efficiently engineered by grafting the native hormones into
      different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR
      fusion proteins were expressed in good yields in mammalian cells and retain
      comparable in vitro biological activity to the native hormones. Pharmacological
      studies in rodents indicated a 20- to 100-fold increase in plasma circulating
      half-life for these antibody agonists and significantly extended in vivo
      activities in the GH-deficient rat model and leptin-deficient obese mouse model
      for the hGH and hLeptin antibody fusions, respectively. These results illustrate
      the utility of antibody CDR fusions as a general and versatile strategy for
      generating long-acting protein therapeutics. 

PMID- 25605878
TI  - Combating pertussis resurgence: One booster vaccination schedule does not fit
      all.
AB  - Pertussis has reemerged as a major public health concern in many countries where
      it was once considered well controlled. Although the mechanisms responsible for
      continued pertussis circulation and resurgence remain elusive and contentious,
      many countries have nevertheless recommended booster vaccinations, the timing and
      number of which vary widely. Here, using a stochastic, age-stratified
      transmission model, we searched for cost-effective booster vaccination strategies
      using a genetic algorithm. We did so assuming four hypothesized mechanisms
      underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II)
      frequent primary vaccine failure, (III) waning of vaccine-derived protection, and
      (IV) vaccine "leakiness." For scenarios I-IV, successful booster strategies were
      identified and varied considerably by mechanism. Especially notable is the
      inability of booster schedules to alleviate resurgence when vaccines are leaky.
      Critically, our findings argue that the ultimate effectiveness of vaccine booster
      schedules will likely depend on correctly pinpointing the causes of resurgence,
      with misdiagnosis of the problem epidemiologically ineffective and economically
      costly. 

PMID- 25605879
TI  - A methyltransferase required for proper timing of the vernalization response in
      Arabidopsis.
AB  - Prolonged exposure to winter cold enables flowering in many plant species through
      a process called vernalization. In Arabidopsis, vernalization results from the
      epigenetic silencing of the floral repressor flowering locus C (FLC) via a
      Polycomb Repressive Complex 2 (PRC2)-mediated increase in the density of the
      epigenetic silencing mark H3K27me3 at FLC chromatin. During cold exposure, a gene
      encoding a unique, cold-specific PRC2 component, vernalization insensitive 3
      (VIN3), which is necessary for PRC2-mediated silencing of FLC, is induced. Here
      we show that set domain group 7 (SDG7) is required for proper timing of VIN3
      induction and of the vernalization process. Loss of SDG7 results in a
      vernalization-hypersensitive phenotype, as well as more rapid cold-mediated up
      regulation of VIN3. In the absence of cold, loss of SDG7 results in elevated
      levels of long noncoding RNAs, which are thought to participate in epigenetic
      repression of FLC. Furthermore, loss of SDG7 results in increased H3K27me3
      deposition on FLC chromatin in the absence of cold exposure and enhanced H3K27me3
      spreading during cold treatment. Thus, SDG7 is a negative regulator of
      vernalization, and loss of SDG7 creates a partially vernalized state without cold
      exposure.

PMID- 25605880
TI  - Reductions in emissions from deforestation from Indonesia's moratorium on new oil
      palm, timber, and logging concessions.
AB  - To reduce greenhouse gas emissions from deforestation, Indonesia instituted a
      nationwide moratorium on new license areas ("concessions") for oil palm
      plantations, timber plantations, and logging activity on primary forests and peat
      lands after May 2011. Here we indirectly evaluate the effectiveness of this
      policy using annual nationwide data on deforestation, concession licenses, and
      potential agricultural revenue from the decade preceding the moratorium. We
      estimate that on average granting a concession for oil palm, timber, or logging
      in Indonesia increased site-level deforestation rates by 17-127%, 44-129%, or 3.1
      11.1%, respectively, above what would have occurred otherwise. We further
      estimate that if Indonesia's moratorium had been in place from 2000 to 2010, then
      nationwide emissions from deforestation over that decade would have been 241-615
      MtCO2e (2.8-7.2%) lower without leakage, or 213-545 MtCO2e (2.5-6.4%) lower with
      leakage. As a benchmark, an equivalent reduction in emissions could have been
      achieved using a carbon price-based instrument at a carbon price of $3.30
      7.50/tCO2e (mandatory) or $12.95-19.45/tCO2e (voluntary). For Indonesia to have
      achieved its target of reducing emissions by 26%, the geographic scope of the
      moratorium would have had to expand beyond new concessions (15.0% of emissions
      from deforestation and peat degradation) to also include existing concessions
      (21.1% of emissions) and address deforestation outside of concessions and
      protected areas (58.7% of emissions). Place-based policies, such as moratoria,
      may be best thought of as bridge strategies that can be implemented rapidly while
      the institutions necessary to enable carbon price-based instruments are
      developed. 

PMID- 25605881
TI  - Cross-evaluation of metrics to estimate the significance of creative works.
AB  - In a world overflowing with creative works, it is useful to be able to filter out
      the unimportant works so that the significant ones can be identified and thereby
      absorbed. An automated method could provide an objective approach for evaluating
      the significance of works on a universal scale. However, there have been few
      attempts at creating such a measure, and there are few "ground truths" for
      validating the effectiveness of potential metrics for significance. For movies,
      the US Library of Congress's National Film Registry (NFR) contains American films
      that are "culturally, historically, or aesthetically significant" as chosen
      through a careful evaluation and deliberation process. By analyzing a network of
      citations between 15,425 United States-produced films procured from the Internet
      Movie Database (IMDb), we obtain several automated metrics for significance. The
      best of these metrics is able to indicate a film's presence in the NFR at least
      as well or better than metrics based on aggregated expert opinions or large
      population surveys. Importantly, automated metrics can easily be applied to older
      films for which no other rating may be available. Our results may have
      implications for the evaluation of other creative works such as scientific
      research. 

PMID- 25605882
TI  - Locally adaptive, spatially explicit projection of US population for 2030 and
      2050.
AB  - Localized adverse events, including natural hazards, epidemiological events, and
      human conflict, underscore the criticality of quantifying and mapping current
      population. Building on the spatial interpolation technique previously developed
      for high-resolution population distribution data (LandScan Global and LandScan
      USA), we have constructed an empirically informed spatial distribution of
      projected population of the contiguous United States for 2030 and 2050, depicting
      one of many possible population futures. Whereas most current large-scale,
      spatially explicit population projections typically rely on a population gravity
      model to determine areas of future growth, our projection model departs from
      these by accounting for multiple components that affect population distribution.
      Modeled variables, which included land cover, slope, distances to larger cities,
      and a moving average of current population, were locally adaptive and
      geographically varying. The resulting weighted surface was used to determine
      which areas had the greatest likelihood for future population change. Population
      projections of county level numbers were developed using a modified version of
      the US Census's projection methodology, with the US Census's official projection
      as the benchmark. Applications of our model include incorporating multiple
      various scenario-driven events to produce a range of spatially explicit
      population futures for suitability modeling, service area planning for
      governmental agencies, consequence assessment, mitigation planning and
      implementation, and assessment of spatially vulnerable populations. 

PMID- 25605883
TI  - Hierarchical cultural values predict success and mortality in high-stakes teams.
AB  - Functional accounts of hierarchy propose that hierarchy increases group
      coordination and reduces conflict. In contrast, dysfunctional accounts claim that
      hierarchy impairs performance by preventing low-ranking team members from voicing
      their potentially valuable perspectives and insights. The current research
      presents evidence for both the functional and dysfunctional accounts of hierarchy
      within the same dataset. Specifically, we offer empirical evidence that
      hierarchical cultural values affect the outcomes of teams in high-stakes
      environments through group processes. Experimental data from a sample of expert
      mountain climbers from 27 countries confirmed that climbers expect that a
      hierarchical culture leads to improved team coordination among climbing teams,
      but impaired psychological safety and information sharing compared with an
      egalitarian culture. An archival analysis of 30,625 Himalayan mountain climbers
      from 56 countries on 5,104 expeditions found that hierarchy both elevated and
      killed in the Himalayas: Expeditions from more hierarchical countries had more
      climbers reach the summit, but also more climbers die along the way. Importantly,
      we established the role of group processes by showing that these effects occurred
      only for group, but not solo, expeditions. These findings were robust to
      controlling for environmental factors, risk preferences, expedition-level
      characteristics, country-level characteristics, and other cultural values.
      Overall, this research demonstrates that endorsing cultural values related to
      hierarchy can simultaneously improve and undermine group performance. 

PMID- 25605884
TI  - Probabilistic evaluation of integrating resource recovery into wastewater
      treatment to improve environmental sustainability.
AB  - Global expectations for wastewater service infrastructure have evolved over time,
      and the standard treatment methods used by wastewater treatment plants (WWTPs)
      are facing issues related to problem shifting due to the current emphasis on
      sustainability. A transition in WWTPs toward reuse of wastewater-derived
      resources is recognized as a promising solution for overcoming these obstacles.
      However, it remains uncertain whether this approach can reduce the environmental
      footprint of WWTPs. To test this hypothesis, we conducted a net environmental
      benefit calculation for several scenarios for more than 50 individual countries
      over a 20-y time frame. For developed countries, the resource recovery approach
      resulted in ~154% net increase in the environmental performance of WWTPs compared
      with the traditional substance elimination approach, whereas this value decreased
      to ~60% for developing countries. Subsequently, we conducted a probabilistic
      analysis integrating these estimates with national values and determined that, if
      this transition was attempted for WWTPs in developed countries, it would have a
      ~65% probability of attaining net environmental benefits. However, this estimate
      decreased greatly to ~10% for developing countries, implying a substantial risk
      of failure. These results suggest that implementation of this transition for
      WWTPs should be studied carefully in different temporal and spatial contexts.
      Developing countries should customize their approach to realizing more
      sustainable WWTPs, rather than attempting to simply replicate the successful
      models of developed countries. Results derived from the model forecasting
      highlight the role of bioenergy generation and reduced use of chemicals in
      improving the sustainability of WWTPs in developing countries. 

PMID- 25605885
TI  - Ghrelin receptor conformational dynamics regulate the transition from a
      preassembled to an active receptor:Gq complex.
AB  - How G protein-coupled receptor conformational dynamics control G protein coupling
      to trigger signaling is a key but still open question. We addressed this question
      with a model system composed of the purified ghrelin receptor assembled into
      lipid discs. Combining receptor labeling through genetic incorporation of
      unnatural amino acids, lanthanide resonance energy transfer, and normal mode
      analyses, we directly demonstrate the occurrence of two distinct receptor:Gq
      assemblies with different geometries whose relative populations parallel the
      activation state of the receptor. The first of these assemblies is a preassembled
      complex with the receptor in its basal conformation. This complex is specific of
      Gq and is not observed with Gi. The second one is an active assembly in which the
      receptor in its active conformation triggers G protein activation. The active
      complex is present even in the absence of agonist, in a direct relationship with
      the high constitutive activity of the ghrelin receptor. These data provide direct
      evidence of a mechanism for ghrelin receptor-mediated Gq signaling in which
      transition of the receptor from an inactive to an active conformation is
      accompanied by a rearrangement of a preassembled receptor:G protein complex,
      ultimately leading to G protein activation and signaling. 

PMID- 25605886
TI  - Asymmetrical effects of unilateral right or left amygdala damage on auditory
      cortical processing of vocal emotions.
AB  - We tested whether human amygdala lesions impair vocal processing in intact
      cortical networks. In two functional MRI experiments, patients with unilateral
      amygdala resection either listened to voices and nonvocal sounds or heard
      binaural vocalizations with attention directed toward or away from emotional
      information on one side. In experiment 1, all patients showed reduced activation
      to voices in the ipsilesional auditory cortex. In experiment 2, emotional voices
      evoked increased activity in both the auditory cortex and the intact amygdala for
      right-damaged patients, whereas no such effects were found for left-damaged
      amygdala patients. Furthermore, the left inferior frontal cortex was functionally
      connected with the intact amygdala in right-damaged patients, but only with
      homologous right frontal areas and not with the amygdala in left-damaged
      patients. Thus, unilateral amygdala damage leads to globally reduced ipsilesional
      cortical voice processing, but only left amygdala lesions are sufficient to
      suppress the enhanced auditory cortical processing of vocal emotions. 

PMID- 25605888
TI  - Twentieth-century shifts in forest structure in California: Denser forests,
      smaller trees, and increased dominance of oaks.
AB  - We document changes in forest structure between historical (1930s) and
      contemporary (2000s) surveys of California vegetation through comparisons of tree
      abundance and size across the state and within several ecoregions. Across
      California, tree density in forested regions increased by 30% between the two
      time periods, whereas forest biomass in the same regions declined, as indicated
      by a 19% reduction in basal area. These changes reflect a demographic shift in
      forest structure: larger trees (>61 cm diameter at breast height) have declined,
      whereas smaller trees (<30 cm) have increased. Large tree declines were found in
      all surveyed regions of California, whereas small tree increases were found in
      every region except the south and central coast. Large tree declines were more
      severe in areas experiencing greater increases in climatic water deficit since
      the 1930s, based on a hydrologic model of water balance for historical climates
      through the 20th century. Forest composition in California in the last century
      has also shifted toward increased dominance by oaks relative to pines, a pattern
      consistent with warming and increased water stress, and also with paleohistoric
      shifts in vegetation in California over the last 150,000 y. 

PMID- 25605887
TI  - Social discounting involves modulation of neural value signals by temporoparietal
      junction.
AB  - Most people are generous, but not toward everyone alike: generosity usually
      declines with social distance between individuals, a phenomenon called social
      discounting. Despite the pervasiveness of social discounting, social distance
      between actors has been surprisingly neglected in economic theory and
      neuroscientific research. We used functional magnetic resonance imaging (fMRI) to
      study the neural basis of this process to understand the neural underpinnings of
      social decision making. Participants chose between selfish and generous
      alternatives, yielding either a large reward for the participant alone, or
      smaller rewards for the participant and another individual at a particular social
      distance. We found that generous choices engaged the temporoparietal junction
      (TPJ). In particular, the TPJ activity was scaled to the social-distance
      dependent conflict between selfish and generous motives during prosocial choice,
      consistent with ideas that the TPJ promotes generosity by facilitating overcoming
      egoism bias. Based on functional coupling data, we propose and provide evidence
      for a biologically plausible neural model according to which the TPJ supports
      social discounting by modulating basic neural value signals in the ventromedial
      prefrontal cortex to incorporate social-distance-dependent other-regarding
      preferences into an otherwise exclusively own-reward value representation. 

PMID- 25605889
TI  - Purinosome formation as a function of the cell cycle.
AB  - The de novo purine biosynthetic pathway relies on six enzymes to catalyze the
      conversion of phosphoribosylpyrophosphate to inosine 5'-monophosphate. Under
      purine-depleted conditions, these enzymes form a multienzyme complex known as the
      purinosome. Previous studies have revealed the spatial organization and
      importance of the purinosome within mammalian cancer cells. In this study, time
      lapse fluorescence microscopy was used to investigate the cell cycle dependency
      on purinosome formation in two cell models. Results in HeLa cells under purine
      depleted conditions demonstrated a significantly higher number of cells with
      purinosomes in the G1 phase, which was further confirmed by cell synchronization.
      HGPRT-deficient fibroblast cells also exhibited the greatest purinosome formation
      in the G1 phase; however, elevated levels of purinosomes were also observed in
      the S and G2/M phases. The observed variation in cell cycle-dependent purinosome
      formation between the two cell models tested can be attributed to differences in
      purine biosynthetic mechanisms. Our results demonstrate that purinosome formation
      is closely related to the cell cycle. 

PMID- 25605890
TI  - Abrupt tectonics and rapid slab detachment with grain damage.
AB  - A simple model for necking and detachment of subducting slabs is developed to
      include the coupling between grain-sensitive rheology and grain-size evolution
      with damage. Necking is triggered by thickened buoyant crust entrained into a
      subduction zone, in which case grain damage accelerates necking and allows for
      relatively rapid slab detachment, i.e., within 1 My, depending on the size of the
      crustal plug. Thick continental crustal plugs can cause rapid necking while
      smaller plugs characteristic of ocean plateaux cause slower necking; oceanic
      lithosphere with normal or slightly thickened crust subducts without necking. The
      model potentially explains how large plateaux or continental crust drawn into
      subduction zones can cause slab loss and rapid changes in plate motion and/or
      induce abrupt continental rebound. 

PMID- 25605891
TI  - Population dynamics of islet-infiltrating cells in autoimmune diabetes.
AB  - Type-1 diabetes in the nonobese diabetic (NOD) mouse starts with an insulitis
      stage, wherein a mixed population of leukocytes invades the pancreas, followed by
      overt diabetes once enough insulin-producing beta-cells are destroyed by invading
      immunocytes. Little is known of the dynamics of lymphocyte movement into the
      pancreas during disease progression. We used the Kaede transgenic mouse, whose
      photoconvertible fluorescent reporter permits noninvasive labeling and subsequent
      tracking of immunocytes, to investigate pancreatic infiltrate dynamics and the
      requirement for antigen specificity during progression of autoimmune diabetes in
      the unmanipulated NOD mouse. Our results indicate that the insulitic lesion is
      very open with constant cell influx and active turnover, predominantly of B and T
      lymphocytes, but also CD11b(+)c(+) myeloid cells. Both naive- and memory
      phenotype lymphocytes trafficked to the insulitis, but Foxp3(+) regulatory T
      cells circulated less than their conventional CD4(+) counterparts. Receptor
      specificity for pancreatic antigens seemed irrelevant for this homing, because
      similar kinetics were observed in polyclonal and antigen-specific transgenic
      contexts. This "open" configuration was also observed after reversal of overt
      diabetes by anti-CD3 treatment. These results portray insulitis as a dynamic
      lesion at all stages of disease, continuously fed by a mixed influx of
      immunocytes, and thus susceptible to evolve over time in response to immunologic
      or environmental influences. 

PMID- 25605892
TI  - Mechanism of RNA polymerase II bypass of oxidative cyclopurine DNA lesions.
AB  - In human cells, the oxidative DNA lesion 8,5'-cyclo-2'-deoxyadenosine (CydA)
      induces prolonged stalling of RNA polymerase II (Pol II) followed by
      transcriptional bypass, generating both error-free and mutant transcripts with
      AMP misincorporated immediately downstream from the lesion. Here, we present
      biochemical and crystallographic evidence for the mechanism of CydA recognition.
      Pol II stalling results from impaired loading of the template base (5') next to
      CydA into the active site, leading to preferential AMP misincorporation. Such
      predominant AMP insertion, which also occurs at an abasic site, is unaffected by
      the identity of the 5'-templating base, indicating that it derives from
      nontemplated synthesis according to an A rule known for DNA polymerases and
      recently identified for Pol II bypass of pyrimidine dimers. Subsequent to AMP
      misincorporation, Pol II encounters a major translocation block that is slowly
      overcome. Thus, the translocation block combined with the poor extension of the
      dA.rA mispair reduce transcriptional mutagenesis. Moreover, increasing the active
      site flexibility by mutation in the trigger loop, which increases the ability of
      Pol II to accommodate the bulky lesion, and addition of transacting factor TFIIF
      facilitate CydA bypass. Thus, blocking lesion entry to the active site,
      translesion A rule synthesis, and translocation block are common features of
      transcription across different bulky DNA lesions. 

PMID- 25605893
TI  - A comparison of worldwide phonemic and genetic variation in human populations.
AB  - Worldwide patterns of genetic variation are driven by human demographic history.
      Here, we test whether this demographic history has left similar signatures on
      phonemes-sound units that distinguish meaning between words in languages-to those
      it has left on genes. We analyze, jointly and in parallel, phoneme inventories
      from 2,082 worldwide languages and microsatellite polymorphisms from 246
      worldwide populations. On a global scale, both genetic distance and phonemic
      distance between populations are significantly correlated with geographic
      distance. Geographically close language pairs share significantly more phonemes
      than distant language pairs, whether or not the languages are closely related.
      The regional geographic axes of greatest phonemic differentiation correspond to
      axes of genetic differentiation, suggesting that there is a relationship between
      human dispersal and linguistic variation. However, the geographic distribution of
      phoneme inventory sizes does not follow the predictions of a serial founder
      effect during human expansion out of Africa. Furthermore, although geographically
      isolated populations lose genetic diversity via genetic drift, phonemes are not
      subject to drift in the same way: within a given geographic radius, languages
      that are relatively isolated exhibit more variance in number of phonemes than
      languages with many neighbors. This finding suggests that relatively isolated
      languages are more susceptible to phonemic change than languages with many
      neighbors. Within a language family, phoneme evolution along genetic, geographic,
      or cognate-based linguistic trees predicts similar ancestral phoneme states to
      those predicted from ancient sources. More genetic sampling could further
      elucidate the relative roles of vertical and horizontal transmission in phoneme
      evolution. 

PMID- 25605894
TI  - Synergistic and antagonistic interactions between bednets and vaccines in the
      control of malaria.
AB  - It is extremely likely that the malaria vaccines currently in development will be
      used in conjunction with treated bednets and other forms of malaria control. The
      interaction of different intervention methods is at present poorly understood in
      a disease such as malaria where immunity is more complex than for other pathogens
      that have been successfully controlled by vaccination. Here we develop a general
      mathematical model of malaria transmission to examine the interaction between
      vaccination and bednets. Counterintuitively, we find that the frailty of malaria
      immunity will potentially cause both synergistic and antagonistic interactions
      between vaccination and the use of bednets. We explore the conditions that create
      these tensions, and outline strategies that minimize their detrimental impact.
      Our analysis specifically considers the three leading vaccine classes currently
      in development: preerythrocytic (PEV), blood stage (BSV), and transmission
      blocking (TBV). We find that the combination of BSV with treated bednets can lead
      to increased morbidity with no added value in terms of elimination; the
      interaction is clearly antagonistic. In contrast, there is strong synergy between
      PEV and treated bednets that may facilitate elimination, although transient
      stages are likely to increase morbidity. The combination of TBV with treated
      bednets is synergistic, lowering both morbidity and elimination thresholds. Our
      results suggest that vaccines will not provide a straightforward solution to
      malaria control, and that future programs need to consider the synergistic and
      antagonistic interactions between vaccines and treated bednets. 

PMID- 25605895
TI  - Pharmacological activation of myosin II paralogs to correct cell mechanics
      defects.
AB  - Current approaches to cancer treatment focus on targeting signal transduction
      pathways. Here, we develop an alternative system for targeting cell mechanics for
      the discovery of novel therapeutics. We designed a live-cell, high-throughput
      chemical screen to identify mechanical modulators. We characterized 4
      hydroxyacetophenone (4-HAP), which enhances the cortical localization of the
      mechanoenzyme myosin II, independent of myosin heavy-chain phosphorylation, thus
      increasing cellular cortical tension. To shift cell mechanics, 4-HAP requires
      myosin II, including its full power stroke, specifically activating human myosin
      IIB (MYH10) and human myosin IIC (MYH14), but not human myosin IIA (MYH9). We
      further demonstrated that invasive pancreatic cancer cells are more deformable
      than normal pancreatic ductal epithelial cells, a mechanical profile that was
      partially corrected with 4-HAP, which also decreased the invasion and migration
      of these cancer cells. Overall, 4-HAP modifies nonmuscle myosin II-based cell
      mechanics across phylogeny and disease states and provides proof of concept that
      cell mechanics offer a rich drug target space, allowing for possible corrective
      modulation of tumor cell behavior. 

PMID- 25605896
TI  - Intracellular and extracellular forces drive primary cilia movement.
AB  - Primary cilia are ubiquitous, microtubule-based organelles that play diverse
      roles in sensory transduction in many eukaryotic cells. They interrogate the
      cellular environment through chemosensing, osmosensing, and mechanosensing using
      receptors and ion channels in the ciliary membrane. Little is known about the
      mechanical and structural properties of the cilium and how these properties
      contribute to ciliary perception. We probed the mechanical responses of primary
      cilia from kidney epithelial cells [Madin-Darby canine kidney-II (MDCK-II)],
      which sense fluid flow in renal ducts. We found that, on manipulation with an
      optical trap, cilia deflect by bending along their length and pivoting around an
      effective hinge located below the basal body. The calculated bending rigidity
      indicates weak microtubule doublet coupling. Primary cilia of MDCK cells lack
      interdoublet dynein motors. Nevertheless, we found that the organelles display
      active motility. 3D tracking showed correlated fluctuations of the cilium and
      basal body. These angular movements seemed random but were dependent on ATP and
      cytoplasmic myosin-II in the cell cortex. We conclude that force generation by
      the actin cytoskeleton surrounding the basal body results in active ciliary
      movement. We speculate that actin-driven ciliary movement might tune and
      calibrate ciliary sensory functions. 

PMID- 25605897
TI  - Microtubule-targeting agents augment the toxicity of DNA-damaging agents by
      disrupting intracellular trafficking of DNA repair proteins.
AB  - The paradigm that microtubule-targeting agents (MTAs) cause cell death via
      mitotic arrest applies to rapidly dividing cells but cannot explain MTA activity
      in slowly growing human cancers. Many preferred cancer regimens combine a MTA
      with a DNA-damaging agent (DDA). We hypothesized that MTAs synergize with DDAs by
      interfering with trafficking of DNA repair proteins on interphase microtubules.
      We investigated nine proteins involved in DNA repair: ATM, ATR, DNA-PK, Rad50,
      Mre11, p95/NBS1, p53, 53BP1, and p63. The proteins were sequestered in the
      cytoplasm by vincristine and paclitaxel but not by an aurora kinase inhibitor,
      colocalized with tubulin by confocal microscopy and coimmunoprecipitated with the
      microtubule motor dynein. Furthermore, adding MTAs to radiation, doxorubicin, or
      etoposide led to more sustained gamma-H2AX levels. We conclude DNA damage-repair
      proteins traffic on microtubules and addition of MTAs sequesters them in the
      cytoplasm, explaining why MTA/DDA combinations are common anticancer regimens. 

PMID- 25605898
TI  - Microbial denitrification dominates nitrate losses from forest ecosystems.
AB  - Denitrification removes fixed nitrogen (N) from the biosphere, thereby
      restricting the availability of this key limiting nutrient for terrestrial plant
      productivity. This microbially driven process has been exceedingly difficult to
      measure, however, given the large background of nitrogen gas (N2) in the
      atmosphere and vexing scaling issues associated with heterogeneous soil systems.
      Here, we use natural abundance of N and oxygen isotopes in nitrate (NO3 (-)) to
      examine dentrification rates across six forest sites in southern China and
      central Japan, which span temperate to tropical climates, as well as various
      stand ages and N deposition regimes. Our multiple stable isotope approach across
      soil to watershed scales shows that traditional techniques underestimate
      terrestrial denitrification fluxes by up to 98%, with annual losses of 5.6-30.1
      kg of N per hectare via this gaseous pathway. These N export fluxes are up to
      sixfold higher than NO3 (-) leaching, pointing to widespread dominance of
      denitrification in removing NO3 (-) from forest ecosystems across a range of
      conditions. Further, we report that the loss of NO3 (-) to denitrification
      decreased in comparison to leaching pathways in sites with the highest rates of
      anthropogenic N deposition. 

PMID- 25605900
TI  - Persistence of deeply sourced iron in the Pacific Ocean.
AB  - Biological carbon fixation is limited by the supply of Fe in vast regions of the
      global ocean. Dissolved Fe in seawater is primarily sourced from continental
      mineral dust, submarine hydrothermalism, and sediment dissolution along
      continental margins. However, the relative contributions of these three sources
      to the Fe budget of the open ocean remains contentious. By exploiting the Fe
      stable isotopic fingerprints of these sources, it is possible to trace distinct
      Fe pools through marine environments, and through time using sedimentary records.
      We present a reconstruction of deep-sea Fe isotopic compositions from a Pacific
      Fe-Mn crust spanning the past 76 My. We find that there have been large and
      systematic changes in the Fe isotopic composition of seawater over the Cenozoic
      that reflect the influence of several, distinct Fe sources to the central Pacific
      Ocean. Given that deeply sourced Fe from hydrothermalism and marginal sediment
      dissolution exhibit the largest Fe isotopic variations in modern oceanic
      settings, the record requires that these deep Fe sources have exerted a major
      control over the Fe inventory of the Pacific for the past 76 My. The persistence
      of deeply sourced Fe in the Pacific Ocean illustrates that multiple sources
      contribute to the total Fe budget of the ocean and highlights the importance of
      oceanic circulation in determining if deeply sourced Fe is ever ventilated at the
      surface. 

PMID- 25605899
TI  - Higd1a is a positive regulator of cytochrome c oxidase.
AB  - Cytochrome c oxidase (CcO) is the only enzyme that uses oxygen to produce a
      proton gradient for ATP production during mitochondrial oxidative
      phosphorylation. Although CcO activity increases in response to hypoxia, the
      underlying regulatory mechanism remains elusive. By screening for hypoxia
      inducible genes in cardiomyocytes, we identified hypoxia inducible domain family,
      member 1A (Higd1a) as a positive regulator of CcO. Recombinant Higd1a directly
      integrated into highly purified CcO and increased its activity. Resonance Raman
      analysis revealed that Higd1a caused structural changes around heme a, the active
      center that drives the proton pump. Using a mitochondria-targeted ATP biosensor,
      we showed that knockdown of endogenous Higd1a reduced oxygen consumption and
      subsequent mitochondrial ATP synthesis, leading to increased cell death in
      response to hypoxia; all of these phenotypes were rescued by exogenous Higd1a.
      These results suggest that Higd1a is a previously unidentified regulatory
      component of CcO, and represents a therapeutic target for diseases associated
      with reduced CcO activity. 

PMID- 25605901
TI  - Kinetics of protein-ligand unbinding: Predicting pathways, rates, and rate
      limiting steps.
AB  - The ability to predict the mechanisms and the associated rate constants of
      protein-ligand unbinding is of great practical importance in drug design. In this
      work we demonstrate how a recently introduced metadynamics-based approach allows
      exploration of the unbinding pathways, estimation of the rates, and determination
      of the rate-limiting steps in the paradigmatic case of the trypsin-benzamidine
      system. Protein, ligand, and solvent are described with full atomic resolution.
      Using metadynamics, multiple unbinding trajectories that start with the ligand in
      the crystallographic binding pose and end with the ligand in the fully solvated
      state are generated. The unbinding rate k off is computed from the mean residence
      time of the ligand. Using our previously computed binding affinity we also obtain
      the binding rate k on. Both rates are in agreement with reported experimental
      values. We uncover the complex pathways of unbinding trajectories and describe
      the critical rate-limiting steps with unprecedented detail. Our findings
      illuminate the role played by the coupling between subtle protein backbone
      fluctuations and the solvation by water molecules that enter the binding pocket
      and assist in the breaking of the shielded hydrogen bonds. We expect our approach
      to be useful in calculating rates for general protein-ligand systems and a valid
      support for drug design.

PMID- 25605902
TI  - Mitochondrial alarmins released by degenerating motor axon terminals activate
      perisynaptic Schwann cells.
AB  - An acute and highly reproducible motor axon terminal degeneration followed by
      complete regeneration is induced by some animal presynaptic neurotoxins,
      representing an appropriate and controlled system to dissect the molecular
      mechanisms underlying degeneration and regeneration of peripheral nerve
      terminals. We have previously shown that nerve terminals exposed to spider or
      snake presynaptic neurotoxins degenerate as a result of calcium overload and
      mitochondrial failure. Here we show that toxin-treated primary neurons release
      signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial
      DNA, and cytochrome c. These molecules activate isolated primary Schwann cells,
      Schwann cells cocultured with neurons and at neuromuscular junction in vivo
      through the MAPK pathway. We propose that this inter- and intracellular signaling
      is involved in triggering the regeneration of peripheral nerve terminals affected
      by other forms of neurodegenerative diseases. 

PMID- 25605903
TI  - Retroviral envelope gene captures and syncytin exaptation for placentation in
      marsupials.
AB  - Syncytins are genes of retroviral origin captured by eutherian mammals, with a
      role in placentation. Here we show that some marsupials-which are the closest
      living relatives to eutherian mammals, although they diverged from the latter
      ~190 Mya-also possess a syncytin gene. The gene identified in the South American
      marsupial opossum and dubbed syncytin-Opo1 has all of the characteristic features
      of a bona fide syncytin gene: It is fusogenic in an ex vivo cell-cell fusion
      assay; it is specifically expressed in the short-lived placenta at the level of
      the syncytial feto-maternal interface; and it is conserved in a functional state
      in a series of Monodelphis species. We further identify a nonfusogenic retroviral
      envelope gene that has been conserved for >80 My of evolution among all
      marsupials (including the opossum and the Australian tammar wallaby), with
      evidence for purifying selection and conservation of a canonical
      immunosuppressive domain, but with only limited expression in the placenta. This
      unusual captured gene, together with a third class of envelope genes from
      recently endogenized retroviruses-displaying strong expression in the uterine
      glands where retroviral particles can be detected-plausibly correspond to the
      different evolutionary statuses of a captured retroviral envelope gene, with only
      syncytin-Opo1 being the present-day bona fide syncytin active in the opossum and
      related species. This study would accordingly recapitulate the natural history of
      syncytin exaptation and evolution in a single species, and definitely extends the
      presence of such genes to all major placental mammalian clades. 

PMID- 25605904
TI  - PSB27: A thylakoid protein enabling Arabidopsis to adapt to changing light
      intensity.
AB  - In earlier studies we have identified FKBP20-2 and CYP38 as soluble proteins of
      the chloroplast thylakoid lumen that are required for the formation of
      photosystem II supercomplexes (PSII SCs). Subsequent work has identified another
      potential candidate functional in SC formation (PSB27). We have followed up on
      this possibility and isolated mutants defective in the PSB27 gene. In addition to
      lack of PSII SCs, mutant plants were severely stunted when cultivated with light
      of variable intensity. The stunted growth was associated with lower PSII
      efficiency and defective starch accumulation. In response to high light exposure,
      the mutant plants also displayed enhanced ROS production, leading to decreased
      biosynthesis of anthocyanin. Unexpectedly, we detected a second defect in the
      mutant, namely in CP26, an antenna protein known to be required for the formation
      of PSII SCs that has been linked to state transitions. Lack of PSII SCs was found
      to be independent of PSB27, but was due to a mutation in the previously described
      cp26 gene that we found had no effect on light adaptation. The present results
      suggest that PSII SCs, despite being required for state transitions, are not
      associated with acclimation to changing light intensity. Our results are
      consistent with the conclusion that PSB27 plays an essential role in enabling
      plants to adapt to fluctuating light intensity through a mechanism distinct from
      photosystem II supercomplexes and state transitions. 

PMID- 25605905
TI  - Real-time resolution of point mutations that cause phenovariance in mice.
AB  - With the wide availability of massively parallel sequencing technologies, genetic
      mapping has become the rate limiting step in mammalian forward genetics. Here we
      introduce a method for real-time identification of N-ethyl-N-nitrosourea-induced
      mutations that cause phenotypes in mice. All mutations are identified by whole
      exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice
      before phenotypic assessment. Quantitative and qualitative traits, including
      lethal effects, in single or multiple combined pedigrees are then analyzed with
      Linkage Analyzer, a software program that detects significant linkage between
      individual mutations and aberrant phenotypic scores and presents processed data
      as Manhattan plots. As multiple alleles of genes are acquired through
      mutagenesis, pooled "superpedigrees" are created to analyze the effects. Our
      method is distinguished from conventional forward genetic methods because it
      permits (1) unbiased declaration of mappable phenotypes, including those that are
      incompletely penetrant (2), automated identification of causative mutations
      concurrent with phenotypic screening, without the need to outcross mutant mice to
      another strain and backcross them, and (3) exclusion of genes not involved in
      phenotypes of interest. We validated our approach and Linkage Analyzer for the
      identification of 47 mutations in 45 previously known genes causative for
      adaptive immune phenotypes; our analysis also implicated 474 genes not previously
      associated with immune function. The method described here permits forward
      genetic analysis in mice, limited only by the rates of mutant production and
      screening. 

PMID- 25605906
TI  - NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily
      divergent calmodulin-dependent mechanisms.
AB  - Nicotinamide adenine dinucleotide phosphate (NADP) is a critical cofactor during
      metabolism, calcium signaling, and oxidative defense, yet how animals regulate
      their NADP pools in vivo and how NADP-synthesizing enzymes are regulated have
      long remained unknown. Here we show that expression of Nadk, an NAD(+) kinase
      encoding gene, governs NADP biosynthesis in vivo and is essential for development
      in Xenopus frog embryos. Unexpectedly, we found that embryonic Nadk expression is
      dynamic, showing cell type-specific up-regulation during both frog and sea urchin
      embryogenesis. We analyzed the NAD kinases (NADKs) of a variety of deuterostome
      animals, finding two conserved internal domains forming a catalytic core but a
      highly divergent N terminus. One type of N terminus (found in basal species such
      as the sea urchin) mediates direct catalytic activation of NADK by
      Ca(2+)/calmodulin (CaM), whereas the other (typical for vertebrates) is
      phosphorylated by a CaM kinase-dependent mechanism. This work indicates that
      animal NADKs govern NADP biosynthesis in vivo and are regulated by evolutionarily
      divergent and conserved CaM-dependent mechanisms. 

PMID- 25605907
TI  - Structural insights into mis-regulation of protein kinase A in human tumors.
AB  - The extensively studied cAMP-dependent protein kinase A (PKA) is involved in the
      regulation of critical cell processes, including metabolism, gene expression, and
      cell proliferation; consequentially, mis-regulation of PKA signaling is
      implicated in tumorigenesis. Recent genomic studies have identified recurrent
      mutations in the catalytic subunit of PKA in tumors associated with Cushing's
      syndrome, a kidney disorder leading to excessive cortisol production, and also in
      tumors associated with fibrolamellar hepatocellular carcinoma (FL-HCC), a rare
      liver cancer. Expression of a L205R point mutant and a DnaJ-PKA fusion protein
      were found to be linked to Cushing's syndrome and FL-HCC, respectively. Here we
      reveal contrasting mechanisms for increased PKA signaling at the molecular level
      through structural determination and biochemical characterization of the aberrant
      enzymes. In the Cushing's syndrome disorder, we find that the L205R mutation
      abolishes regulatory-subunit binding, leading to constitutive, cAMP-independent
      signaling. In FL-HCC, the DnaJ-PKA chimera remains under regulatory subunit
      control; however, its overexpression from the DnaJ promoter leads to enhanced
      cAMP-dependent signaling. Our findings provide a structural understanding of the
      two distinct disease mechanisms and they offer a basis for designing effective
      drugs for their treatment. 

PMID- 25605908
TI  - The guanine nucleotide exchange factor Ric-8A induces domain separation and Ras
      domain plasticity in Galphai1.
AB  - Heterotrimeric G proteins are activated by exchange of GDP for GTP at the G
      protein alpha subunit (Galpha), most notably by G protein-coupled transmembrane
      receptors. Ric-8A is a soluble cytoplasmic protein essential for embryonic
      development that acts as both a guanine nucleotide exchange factor (GEF) and a
      chaperone for Galpha subunits of the i, q, and 12/13 classes. Previous studies
      demonstrated that Ric-8A stabilizes a dynamically disordered state of nucleotide
      free Galpha as the catalytic intermediate for nucleotide exchange, but no
      information was obtained on the structures involved or the magnitude of the
      structural fluctuations. In the present study, site-directed spin labeling (SDSL)
      together with double electron-electron resonance (DEER) spectroscopy is used to
      provide global distance constraints that identify discrete members of a
      conformational ensemble in the Galphai1:Ric-8A complex and the magnitude of
      structural differences between them. In the complex, the helical and Ras-like
      nucleotide-binding domains of Galphai1 pivot apart to occupy multiple resolved
      states with displacements as large as 25 A. The domain displacement appears to be
      distinct from that observed in Galphas upon binding of Gs to the beta2 adrenergic
      receptor. Moreover, the Ras-like domain exhibits structural plasticity within and
      around the nucleotide-binding cavity, and the switch I and switch II regions,
      which are known to adopt different conformations in the GDP- and GTP-bound states
      of Galpha, undergo structural rearrangements. Collectively, the data show that
      Ric-8A induces a conformationally heterogeneous state of Galphai and provide
      insight into the mechanism of action of a nonreceptor Galpha GEF. 

PMID- 25605909
TI  - Autocrine regulation of ecdysone synthesis by beta3-octopamine receptor in the
      prothoracic gland is essential for Drosophila metamorphosis.
AB  - In Drosophila, pulsed production of the steroid hormone ecdysone plays a pivotal
      role in developmental transitions such as metamorphosis. Ecdysone production is
      regulated in the prothoracic gland (PG) by prothoracicotropic hormone (PTTH) and
      insulin-like peptides (Ilps). Here, we show that monoaminergic autocrine
      regulation of ecdysone biosynthesis in the PG is essential for metamorphosis. PG
      specific knockdown of a monoamine G protein-coupled receptor, beta3-octopamine
      receptor (Octbeta3R), resulted in arrested metamorphosis due to lack of ecdysone.
      Knockdown of tyramine biosynthesis genes expressed in the PG caused similar
      defects in ecdysone production and metamorphosis. Moreover, PTTH and Ilps
      signaling were impaired by Octbeta3R knockdown in the PG, and activation of these
      signaling pathways rescued the defect in metamorphosis. Thus, monoaminergic
      autocrine signaling in the PG regulates ecdysone biogenesis in a coordinated
      fashion on activation by PTTH and Ilps. We propose that monoaminergic autocrine
      signaling acts downstream of a body size checkpoint that allows metamorphosis to
      occur when nutrients are sufficiently abundant. 

PMID- 25605910
TI  - Kinetics of sickle cell biorheology and implications for painful vasoocclusive
      crisis.
AB  - We developed a microfluidics-based model to quantify cell-level processes
      modulating the pathophysiology of sickle cell disease (SCD). This in vitro model
      enabled quantitative investigations of the kinetics of cell sickling, unsickling,
      and cell rheology. We created short-term and long-term hypoxic conditions to
      simulate normal and retarded transit scenarios in microvasculature. Using blood
      samples from 25 SCD patients with sickle hemoglobin (HbS) levels varying from 64
      to 90.1%, we investigated how cell biophysical alterations during blood flow
      correlated with hematological parameters, HbS level, and hydroxyurea (HU)
      therapy. From these measurements, we identified two severe cases of SCD that were
      also independently validated as severe from a genotype-based disease severity
      classification. These results point to the potential of this method as a
      diagnostic indicator of disease severity. In addition, we investigated the role
      of cell density in the kinetics of cell sickling. We observed an effect of HU
      therapy mainly in relatively dense cell populations, and that the sickled
      fraction increased with cell density. These results lend support to the
      possibility that the microfluidic platform developed here offers a unique and
      quantitative approach to assess the kinetic, rheological, and hematological
      factors involved in vasoocclusive events associated with SCD and to develop
      alternative diagnostic tools for disease severity to supplement other methods.
      Such insights may also lead to a better understanding of the pathogenic basis and
      mechanism of drug response in SCD. 

PMID- 25605911
TI  - Identification of hydroxyapatite spherules provides new insight into subretinal
      pigment epithelial deposit formation in the aging eye.
AB  - Accumulation of protein- and lipid-containing deposits external to the retinal
      pigment epithelium (RPE) is common in the aging eye, and has long been viewed as
      the hallmark of age-related macular degeneration (AMD). The cause for the
      accumulation and retention of molecules in the sub-RPE space, however, remains an
      enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence
      for the formation of small (0.5-20 MUm in diameter), hollow, hydroxyapatite (HAP)
      spherules in Bruch's membrane in human eyes. These spherules are distinct in
      form, placement, and staining from the well-known calcification of the elastin
      layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS)
      imaging confirmed the presence of calcium phosphate in the spherules and
      identified cholesterol enrichment in their core. Using HAP-selective fluorescent
      dyes, we show that all types of sub-RPE deposits in the macula, as well as in the
      periphery, contain numerous HAP spherules. Immunohistochemical labeling for
      proteins characteristic of sub-RPE deposits, such as complement factor H,
      vitronectin, and amyloid beta, revealed that HAP spherules were coated with these
      proteins. HAP spherules were also found outside the sub-RPE deposits, ready to
      bind proteins at the RPE/choroid interface. Based on these results, we propose a
      novel mechanism for the growth, and possibly even the formation, of sub-RPE
      deposits, namely, that the deposit growth and formation begin with the deposition
      of insoluble HAP shells around naturally occurring, cholesterol-containing
      extracellular lipid droplets at the RPE/choroid interface; proteins and lipids
      then attach to these shells, initiating or supporting the growth of sub-RPE
      deposits. 

PMID- 25605912
TI  - A tablet that shifts the clock.

PMID- 25605913
TI  - Rapid deposition of oxidized biogenic compounds to a temperate forest.
AB  - We report fluxes and dry deposition velocities for 16 atmospheric compounds above
      a southeastern United States forest, including: hydrogen peroxide (H2O2), nitric
      acid (HNO3), hydrogen cyanide (HCN), hydroxymethyl hydroperoxide, peroxyacetic
      acid, organic hydroxy nitrates, and other multifunctional species derived from
      the oxidation of isoprene and monoterpenes. The data suggest that dry deposition
      is the dominant daytime sink for small, saturated oxygenates. Greater than 6 wt
      %C emitted as isoprene by the forest was returned by dry deposition of its
      oxidized products. Peroxides account for a large fraction of the oxidant flux,
      possibly eclipsing ozone in more pristine regions. The measured organic nitrates
      comprise a sizable portion (15%) of the oxidized nitrogen input into the canopy,
      with HNO3 making up the balance. We observe that water-soluble compounds (e.g.,
      strong acids and hydroperoxides) deposit with low surface resistance whereas
      compounds with moderate solubility (e.g., organic nitrates and hydroxycarbonyls)
      or poor solubility (e.g., HCN) exhibited reduced uptake at the surface of plants.
      To first order, the relative deposition velocities of water-soluble compounds are
      constrained by their molecular diffusivity. From resistance modeling, we infer a
      substantial emission flux of formic acid at the canopy level (~1 nmol m(-2)?s(
      1)). GEOS-Chem, a widely used atmospheric chemical transport model, currently
      underestimates dry deposition for most molecules studied in this work.
      Reconciling GEOS-Chem deposition velocities with observations resulted in up to a
      45% decrease in the simulated surface concentration of trace gases. 

PMID- 25605915
TI  - Biomechanical basis of wing and haltere coordination in flies.
AB  - The spectacular success and diversification of insects rests critically on two
      major evolutionary adaptations. First, the evolution of flight, which enhanced
      the ability of insects to colonize novel ecological habitats, evade predators, or
      hunt prey; and second, the miniaturization of their body size, which profoundly
      influenced all aspects of their biology from development to behavior. However,
      miniaturization imposes steep demands on the flight system because smaller
      insects must flap their wings at higher frequencies to generate sufficient
      aerodynamic forces to stay aloft; it also poses challenges to the sensorimotor
      system because precise control of wing kinematics and body trajectories requires
      fast sensory feedback. These tradeoffs are best studied in Dipteran flies in
      which rapid mechanosensory feedback to wing motor system is provided by halteres,
      reduced hind wings that evolved into gyroscopic sensors. Halteres oscillate at
      the same frequency as and precisely antiphase to the wings; they detect body
      rotations during flight, thus providing feedback that is essential for
      controlling wing motion during aerial maneuvers. Although tight phase synchrony
      between halteres and wings is essential for providing proper timing cues, the
      mechanisms underlying this coordination are not well understood. Here, we
      identify specific mechanical linkages within the thorax that passively mediate
      both wing-wing and wing-haltere phase synchronization. We demonstrate that the
      wing hinge must possess a clutch system that enables flies to independently
      engage or disengage each wing from the mechanically linked thorax. In concert
      with a previously described gearbox located within the wing hinge, the clutch
      system enables independent control of each wing. These biomechanical features are
      essential for flight control in flies. 

PMID- 25605914
TI  - Specialized insulin is used for chemical warfare by fish-hunting cone snails.
AB  - More than 100 species of venomous cone snails (genus Conus) are highly effective
      predators of fish. The vast majority of venom components identified and
      functionally characterized to date are neurotoxins specifically targeted to
      receptors, ion channels, and transporters in the nervous system of prey,
      predators, or competitors. Here we describe a venom component targeting energy
      metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus
      geographus and Conus tulipa, have evolved specialized insulins that are expressed
      as major components of their venoms. These insulins are distinctive in having
      much greater similarity to fish insulins than to the molluscan hormone and are
      unique in that posttranslational modifications characteristic of conotoxins
      (hydroxyproline, gamma-carboxyglutamate) are present. When injected into fish,
      the venom insulin elicits hypoglycemic shock, a condition characterized by
      dangerously low blood glucose. Our evidence suggests that insulin is specifically
      used as a weapon for prey capture by a subset of fish-hunting cone snails that
      use a net strategy to capture prey. Insulin appears to be a component of the
      nirvana cabal, a toxin combination in these venoms that is released into the
      water to disorient schools of small fish, making them easier to engulf with the
      snail's distended false mouth, which functions as a net. If an entire school of
      fish simultaneously experiences hypoglycemic shock, this should directly
      facilitate capture by the predatory snail. 

PMID- 25605916
TI  - Quantum dot/antibody conjugates for in vivo cytometric imaging in mice.
AB  - Multiplexed, phenotypic, intravital cytometric imaging requires novel fluorophore
      conjugates that have an appropriate size for long circulation and diffusion and
      show virtually no nonspecific binding to cells/serum while binding to cells of
      interest with high specificity. In addition, these conjugates must be stable and
      maintain a high quantum yield in the in vivo environments. Here, we show that
      this can be achieved using compact (~15 nm in hydrodynamic diameter) and
      biocompatible quantum dot (QD) -Ab conjugates. We developed these conjugates by
      coupling whole mAbs to QDs coated with norbornene-displaying polyimidazole
      ligands using tetrazine-norbornene cycloaddition. Our QD immunoconstructs were
      used for in vivo single-cell labeling in bone marrow. The intravital imaging
      studies using a chronic calvarial bone window showed that our QD-Ab conjugates
      diffuse into the entire bone marrow and efficiently label single cells belonging
      to rare populations of hematopoietic stem and progenitor cells (Sca1(+)c-Kit(+)
      cells). This in vivo cytometric technique may be useful in a wide range of
      structural and functional imaging to study the interactions between cells and
      between a cell and its environment in intact and diseased tissues. 

PMID- 25605917
TI  - Suppression of cancer relapse and metastasis by inhibiting cancer stemness.
AB  - Partial or even complete cancer regression can be achieved in some patients with
      current cancer treatments. However, such initial responses are almost always
      followed by relapse, with the recurrent cancer being resistant to further
      treatments. The discovery of therapeutic approaches that counteract relapse is,
      therefore, essential for advancing cancer medicine. Cancer cells are extremely
      heterogeneous, even in each individual patient, in terms of their malignant
      potential, drug sensitivity, and their potential to metastasize and cause
      relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or
      stemness-high cancer cells, that are highly tumorigenic and metastatic have been
      isolated from cancer patients with a variety of tumor types. Moreover, such
      stemness-high cancer cells are resistant to conventional chemotherapy and
      radiation. Here we show that BBI608, a small molecule identified by its ability
      to inhibit gene transcription driven by Stat3 and cancer stemness properties, can
      inhibit stemness gene expression and block spherogenesis of or kill stemness-high
      cancer cells isolated from a variety of cancer types. Moreover, cancer relapse
      and metastasis were effectively blocked by BBI608 in mice. These data demonstrate
      targeting cancer stemness as a novel approach to develop the next generation of
      cancer therapeutics to suppress cancer relapse and metastasis. 

PMID- 25605918
TI  - Fatty acid synthase is preferentially degraded by autophagy upon nitrogen
      starvation in yeast.
AB  - Autophagy, an evolutionarily conserved intracellular catabolic process, leads to
      the degradation of cytosolic proteins and organelles in the vacuole/lysosome.
      Different forms of selective autophagy have recently been described. Starvation
      induced protein degradation, however, is considered to be nonselective. Here we
      describe a novel interaction between autophagy-related protein 8 (Atg8) and fatty
      acid synthase (FAS), a pivotal enzymatic complex responsible for the entire
      synthesis of C16- and C18-fatty acids in yeast. We show that although FAS
      possesses housekeeping functions, under starvation conditions it is delivered to
      the vacuole for degradation by autophagy in a Vac8- and Atg24-dependent manner.
      We also provide evidence that FAS degradation is essential for survival under
      nitrogen deprivation. Our results imply that during nitrogen starvation specific
      proteins are preferentially recruited into autophagosomes. 

PMID- 25605919
TI  - Dynamics of a morbillivirus at the domestic-wildlife interface: Canine distemper
      virus in domestic dogs and lions.
AB  - Morbilliviruses cause many diseases of medical and veterinary importance, and
      although some (e.g., measles and rinderpest) have been controlled successfully,
      others, such as canine distemper virus (CDV), are a growing concern. A propensity
      for host-switching has resulted in CDV emergence in new species, including
      endangered wildlife, posing challenges for controlling disease in multispecies
      communities. CDV is typically associated with domestic dogs, but little is known
      about its maintenance and transmission in species-rich areas or about the
      potential role of domestic dog vaccination as a means of reducing disease threats
      to wildlife. We address these questions by analyzing a long-term serological
      dataset of CDV in lions and domestic dogs from Tanzania's Serengeti ecosystem.
      Using a Bayesian state-space model, we show that dynamics of CDV have changed
      considerably over the past three decades. Initially, peaks of CDV infection in
      dogs preceded those in lions, suggesting that spill-over from dogs was the main
      driver of infection in wildlife. However, despite dog-to-lion transmission
      dominating cross-species transmission models, infection peaks in lions became
      more frequent and asynchronous from those in dogs, suggesting that other wildlife
      species may play a role in a potentially complex maintenance community.
      Widespread mass vaccination of domestic dogs reduced the probability of infection
      in dogs and the size of outbreaks but did not prevent transmission to or peaks of
      infection in lions. This study demonstrates the complexity of CDV dynamics in
      natural ecosystems and the value of long-term, large-scale datasets for
      investigating transmission patterns and evaluating disease control strategies. 

PMID- 25605920
TI  - Galactose metabolic genes in yeast respond to a ratio of galactose and glucose.
AB  - Natural environments are filled with multiple, often competing, signals. In
      contrast, biological systems are often studied in "well-controlled" environments
      where only a single input is varied, potentially missing important interactions
      between signals. Catabolite repression of galactose by glucose is one of the best
      studied eukaryotic signal integration systems. In this system, it is believed
      that galactose metabolic (GAL) genes are induced only when glucose levels drop
      below a threshold. In contrast, we show that GAL gene induction occurs at a
      constant external galactose:glucose ratio across a wide range of sugar
      concentrations. We systematically perturbed the components of the canonical
      galactose/glucose signaling pathways and found that these components do not
      account for ratio sensing. Instead we provide evidence that ratio sensing occurs
      upstream of the canonical signaling pathway and results from the competitive
      binding of the two sugars to hexose transporters. We show that a mutant that
      behaves as the classical model expects (i.e., cannot use galactose above a
      glucose threshold) has a fitness disadvantage compared with wild type. A number
      of common biological signaling motifs can give rise to ratio sensing, typically
      through negative interactions between opposing signaling molecules. We therefore
      suspect that this previously unidentified nutrient sensing paradigm may be common
      and overlooked in biology. 

PMID- 25605921
TI  - Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15
      conjugation and viral resistance.
AB  - Protein modification by the ubiquitin-like protein ISG15 is an interferon (IFN)
      effector system, which plays a major role in antiviral defense. ISG15
      modification is counteracted by the isopeptidase USP18, a major negative
      regulator of IFN signaling, which was also shown to exert its regulatory function
      in an isopeptidase-independent manner. To dissect enzymatic and nonenzymatic
      functions of USP18 in vivo, we generated knock-in mice (USP18(C61A/C61A))
      expressing enzymatically inactive USP18. USP18(C61A/C61A) mice displayed
      increased levels of ISG15 conjugates, validating that USP18 is a major ISG15
      isopeptidase in vivo. Unlike USP18(-/-) mice, USP18(C61A/C61A) animals did not
      exhibit morphological abnormalities, fatal IFN hypersensitivity, or increased
      lethality, clearly showing that major USP18 functions are unrelated to its
      protease activity. Strikingly, elevated ISGylation in USP18(C61A/C61A) mice was
      accompanied by increased viral resistance against vaccinia virus and influenza B
      virus infections. Enhanced resistance upon influenza B infection in
      USP18(C61A/C61A) mice was completely reversed in USP18(C61A/C61A) mice, which
      additionally lack ISG15, providing evidence that the observed reduction in viral
      titers is ISG15 dependent. These results suggest that increasing ISGylation by
      specific inhibition of USP18 protease activity could constitute a promising
      antiviral strategy with only a minimal risk of severe adverse effects. 

PMID- 25605922
TI  - Endo-beta-N-acetylglucosaminidase forms N-GlcNAc protein aggregates during ER
      associated degradation in Ngly1-defective cells.
AB  - The cytoplasmic peptide:N-glycanase (PNGase; Ngly1 in mice) is a deglycosylating
      enzyme involved in the endoplasmic reticulum (ER)-associated degradation (ERAD)
      process. The precise role of Ngly1 in the ERAD process, however, remains unclear
      in mammals. The findings reported herein, using mouse embryonic fibroblast (MEF)
      cells, that the ablation of Ngly1 causes dysregulation of the ERAD process.
      Interestingly, not only delayed degradation but also the deglycosylation of a
      misfolded glycoprotein was observed in Ngly1(-/-) MEF cells. The unconventional
      deglycosylation reaction was found to be catalyzed by the cytosolic endo-beta-N
      acetylglucosaminidase (ENGase), generating aggregation-prone N-GlcNAc proteins.
      The ERAD dysregulation in cells lacking Ngly1 was restored by the additional
      knockout of ENGase gene. Thus, our study underscores the functional importance of
      Ngly1 in the ERAD process and provides a potential mechanism underlying the
      phenotypic consequences of a newly emerging genetic disorder caused by mutation
      of the human NGLY1 gene. 

PMID- 25605923
TI  - Belief about nicotine selectively modulates value and reward prediction error
      signals in smokers.
AB  - Little is known about how prior beliefs impact biophysically described processes
      in the presence of neuroactive drugs, which presents a profound challenge to the
      understanding of the mechanisms and treatments of addiction. We engineered
      smokers' prior beliefs about the presence of nicotine in a cigarette smoked
      before a functional magnetic resonance imaging session where subjects carried out
      a sequential choice task. Using a model-based approach, we show that smokers'
      beliefs about nicotine specifically modulated learning signals (value and reward
      prediction error) defined by a computational model of mesolimbic dopamine
      systems. Belief of "no nicotine in cigarette" (compared with "nicotine in
      cigarette") strongly diminished neural responses in the striatum to value and
      reward prediction errors and reduced the impact of both on smokers' choices.
      These effects of belief could not be explained by global changes in visual
      attention and were specific to value and reward prediction errors. Thus, by
      modulating the expression of computationally explicit signals important for
      valuation and choice, beliefs can override the physical presence of a potent
      neuroactive compound like nicotine. These selective effects of belief demonstrate
      that belief can modulate model-based parameters important for learning. The
      implications of these findings may be far ranging because belief-dependent
      effects on learning signals could impact a host of other behaviors in addiction
      as well as in other mental health problems. 

PMID- 25605924
TI  - Spata6 is required for normal assembly of the sperm connecting piece and tight
      head-tail conjunction.
AB  - "Pinhead sperm," or "acephalic sperm," a type of human teratozoospermia, refers
      to the condition in which ejaculate contains mostly sperm flagella without heads.
      Family clustering and homogeneity of this syndrome suggests a genetic basis, but
      the causative genes remain largely unknown. Here we report that Spata6, an
      evolutionarily conserved testis-specific gene, encodes a protein required for
      formation of the segmented columns and the capitulum, two major structures of the
      sperm connecting piece essential for linking the developing flagellum to the head
      during late spermiogenesis. Inactivation of Spata6 in mice leads to acephalic
      spermatozoa and male sterility. Our proteomic analyses reveal that SPATA6 is
      involved in myosin-based microfilament transport through interaction with myosin
      subunits (e.g., MYL6). 

PMID- 25605925
TI  - Force-dependent transition in the T-cell receptor beta-subunit allosterically
      regulates peptide discrimination and pMHC bond lifetime.
AB  - The alphabeta T-cell receptor (TCR) on each T lymphocyte mediates exquisite
      specificity for a particular foreign peptide bound to a major histocompatibility
      complex molecule (pMHC) displayed on the surface of altered cells. This
      recognition stimulates protection in the mammalian host against intracellular
      pathogens, including viruses, and involves piconewton forces that accompany pMHC
      ligation. Physical forces are generated by T-lymphocyte movement during immune
      surveillance as well as by cytoskeletal rearrangements at the immunological
      synapse following cessation of cell migration. The mechanistic explanation for
      how TCRs distinguish between foreign and self-peptides bound to a given MHC
      molecule is unclear: peptide residues themselves comprise few of the TCR contacts
      on the pMHC, and pathogen-derived peptides are scant among myriad self-peptides
      bound to the same MHC class arrayed on infected cells. Using optical tweezers and
      DNA tether spacer technology that permit piconewton force application and
      nanometer scale precision, we have determined how bioforces relate to self versus
      nonself discrimination. Single-molecule analyses involving isolated alphabeta
      heterodimers as well as complete TCR complexes on T lymphocytes reveal that the
      FG loop in the beta-subunit constant domain allosterically controls both the
      variable domain module's catch bond lifetime and peptide discrimination via force
      driven conformational transition. In contrast to integrins, the TCR interrogates
      its ligand via a strong force-loaded state with release through a weakened,
      extended state. Our work defines a key element of TCR mechanotransduction,
      explaining why the FG loop structure evolved for adaptive immunity in alphabeta
      but not gammadeltaTCRs or immunoglobulins. 

PMID- 25605926
TI  - Fitness tradeoffs between spores and nonaggregating cells can explain the
      coexistence of diverse genotypes in cellular slime molds.
AB  - Cellular slime molds, including the well-studied Dictyostelium discoideum, are
      amoebae whose life cycle includes both a single-cellular and a multicellular
      stage. To achieve the multicellular stage, individual amoebae aggregate upon
      starvation to form a fruiting body made of dead stalk cells and reproductive
      spores, a process that has been described in terms of cooperation and altruism.
      When amoebae aggregate they do not perfectly discriminate against nonkin, leading
      to chimeric fruiting bodies. Within chimeras, complex interactions among
      genotypes have been documented, which should theoretically reduce genetic
      diversity. This is however inconsistent with the great diversity of genotypes
      found in nature. Recent work has shown that a little-studied component of D.
      discoideum fitness--the loner cells that do not participate in the aggregation-
      can be selected for depending on environmental conditions and that, together with
      the spores, they could represent a bet-hedging strategy. We suggest that in all
      cellular slime molds the existence of loners could resolve the apparent diversity
      paradox in two ways. First, if loners are accounted for, then apparent genotypic
      skew in the spores of chimeras could simply be the result of different
      investments into spores versus loners. Second, in an ecosystem with multiple
      local environments differing in their food recovery characteristics and connected
      globally via weak-to-moderate dispersal, coexistence of multiple genotypes can
      occur. Finally, we argue that the loners make it impossible to define altruistic
      behavior, winners or losers, without a clear description of the ecology.

PMID- 25605927
TI  - BTB-ZF transcriptional regulator PLZF modifies chromatin to restrain inflammatory
      signaling programs.
AB  - Inflammation is critical for host defense, but without appropriate control, it
      can cause chronic disease or even provoke fatal responses. Here we identify a
      mechanism that limits the inflammatory response. Probing the responses of
      macrophages to the key sensory Toll-like receptors, we identify that the Broad
      complex, Tramtrack and Bric-a-brac/poxvirus and zinc finger (BTB/POZ),
      transcriptional regulator promyelocytic leukemia zinc finger (PLZF) limits the
      expression of inflammatory gene products. In accord with this finding, PLZF
      deficient animals express higher levels of potent inflammatory cytokines and
      mount exaggerated inflammatory responses to infectious stimuli. Temporal
      quantitation of inflammatory gene transcripts shows increased gene induction in
      the absence of PLZF. Genome-wide analysis of histone modifications distinguish
      that PLZF establishes basal activity states of early response genes to maintain
      immune homeostasis and limit damaging inflammation. We show that PLZF stabilizes
      a corepressor complex that encompasses histone deacetylase activity to control
      chromatin. Together with our previous demonstration that PLZF promotes the
      antiviral response, these results suggest a strategy that could realize one of
      the major goals of immune therapy to retain immune resistance to pathogens while
      curbing damaging inflammation. 

PMID- 25605928
TI  - Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab
      paclitaxel associates with survival in lung cancer.
AB  - Addition of anti-VEGF antibody therapy to standard chemotherapies has improved
      survival and is an accepted standard of care for advanced non-small cell lung
      cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases
      survival remain unclear. We evaluated dynamic CT-based vascular parameters and
      plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy
      with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore
      potential biomarkers of treatment response and resistance to this regimen. Thirty
      six patients were enrolled in this study. The primary end point was 6-mo
      progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has
      a promising overall response rate of 36% and median time to progression of 8.5
      (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti
      VEGF therapy led to a sustained increase in plasma PlGF, a potential
      pharmacodynamic marker. We also found that higher levels of soluble VEGFR1
      measured before starting bevacizumab with chemotherapy were associated with worse
      survival, supporting its potential role as biomarker of treatment resistance. Our
      imaging biomarker studies indicate that bevacizumab-based treatment-while
      reducing blood flow, volume, and permeability in the overall population-may be
      associated with improved survival in patients with improved tumor vasculature and
      blood perfusion after treatment. This hypothesis-generating study supports the
      notion that excessively decreasing vascular permeability and pruning/rarefaction
      after bevacizumab therapy may negatively impact the outcome of combination
      therapy in NSCLC patients. This hypothesis warrants further dose-titration
      studies of bevacizumab to examine the dose effect on tumor vasculature and
      treatment efficacy. 

PMID- 25605929
TI  - Neuronal UCP1 expression suggests a mechanism for local thermogenesis during
      hibernation.
AB  - Hibernating mammals possess a unique ability to reduce their body temperature to
      ambient levels, which can be as low as -2.9  degrees C, by active down-regulation
      of metabolism. Despite such a depressed physiologic phenotype, hibernators still
      maintain activity in their nervous systems, as evidenced by their continued
      sensitivity to auditory, tactile, and thermal stimulation. The molecular
      mechanisms that underlie this adaptation remain unknown. We report, using
      differential transcriptomics alongside immunohistologic and biochemical analyses,
      that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus)
      express mitochondrial uncoupling protein 1 (UCP1). The expression changes
      seasonally, with higher expression during hibernation compared with the summer
      active state. Functional and pharmacologic analyses show that squirrel UCP1 acts
      as the typical thermogenic protein in vitro. Accordingly, we found that
      mitochondria isolated from torpid squirrel brain show a high level of palmitate
      induced uncoupling. Furthermore, torpid squirrels during the hibernation season
      keep their brain temperature significantly elevated above ambient temperature and
      that of the rest of the body, including brown adipose tissue. Together, our
      findings suggest that UCP1 contributes to local thermogenesis in the squirrel
      brain, and thus supports nervous tissue function at low body temperature during
      hibernation. 

PMID- 25605930
TI  - Endostatin: A novel inhibitor of androgen receptor function in prostate cancer.
AB  - Acquired resistance to androgen receptor (AR)-targeted therapies compels the
      development of novel treatment strategies for castration-resistant prostate
      cancer (CRPC). Here, we report a profound effect of endostatin on prostate cancer
      cells by efficient intracellular trafficking, direct interaction with AR,
      reduction of nuclear AR level, and down-regulation of AR-target gene
      transcription. Structural modeling followed by functional analyses further
      revealed that phenylalanine-rich alpha1-helix in endostatin-which shares
      structural similarity with noncanonical nuclear receptor box in AR-antagonizes AR
      transcriptional activity by occupying the activation function (AF)-2 binding
      interface for coactivators and N-terminal AR AF-1. Together, our data suggest
      that endostatin can be recognized as an endogenous AR inhibitor that impairs
      receptor function through protein-protein interaction. These findings provide new
      insights into endostatin whose antitumor effect is not limited to inhibiting
      angiogenesis, but can be translated to suppressing AR-mediated disease
      progression in CRPC. 

PMID- 25605931
TI  - Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and
      allergic asthma.
AB  - The inductive role of dendritic cells (DC) in Th2 differentiation has not been
      fully defined. We addressed this gap in knowledge by focusing on signaling events
      mediated by the heterotrimeric GTP binding proteins Galphas, and Galphai, which
      respectively stimulate and inhibit the activation of adenylyl cyclases and the
      synthesis of cAMP. We show here that deletion of Gnas, the gene that encodes
      Galphas in mouse CD11c(+) cells (Gnas(DeltaCD11c) mice), and the accompanying
      decrease in cAMP provoke Th2 polarization and yields a prominent allergic
      phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP
      on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain
      gene products made by Gnas(DeltaCD11c) DC affect the Th2 bias. These findings
      imply that G protein-coupled receptors, the physiological regulators of Galphas
      and Galphai activation and cAMP formation, act via PKA to regulate Th bias in DC
      and in turn, Th2-mediated immunopathologies. 

PMID- 25605932
TI  - X-ray crystallographic and EPR spectroscopic analysis of HydG, a maturase in
      [FeFe]-hydrogenase H-cluster assembly.
AB  - Hydrogenases use complex metal cofactors to catalyze the reversible formation of
      hydrogen. In [FeFe]-hydrogenases, the H-cluster cofactor includes a diiron
      subcluster containing azadithiolate, three CO, and two CN(-) ligands. During the
      assembly of the H cluster, the radical S-adenosyl methionine (SAM) enzyme HydG
      lyses the substrate tyrosine to yield the diatomic ligands. These diatomic
      products form an enzyme-bound Fe(CO)x(CN)y synthon that serves as a precursor for
      eventual H-cluster assembly. To further elucidate the mechanism of this complex
      reaction, we report the crystal structure and EPR analysis of HydG. At one end of
      the HydG (betaalpha)8 triosephosphate isomerase (TIM) barrel, a canonical [4Fe
      4S] cluster binds SAM in close proximity to the proposed tyrosine binding site.
      At the opposite end of the active-site cavity, the structure reveals the
      auxiliary Fe-S cluster in two states: one monomer contains a [4Fe-5S] cluster,
      and the other monomer contains a [5Fe-5S] cluster consisting of a [4Fe-4S] cubane
      bridged by a MU2-sulfide ion to a mononuclear Fe(2+) center. This fifth iron is
      held in place by a single highly conserved protein-derived ligand: histidine 265.
      EPR analysis confirms the presence of the [5Fe-5S] cluster, which on incubation
      with cyanide, undergoes loss of the labile iron to yield a [4Fe-4S] cluster. We
      hypothesize that the labile iron of the [5Fe-5S] cluster is the site of
      Fe(CO)x(CN)y synthon formation and that the limited bonding between this iron and
      HydG may facilitate transfer of the intact synthon to its cognate acceptor for
      subsequent H-cluster assembly. 

PMID- 25605933
TI  - MicroRNA-8 targets the Wingless signaling pathway in the female mosquito fat body
      to regulate reproductive processes.
AB  - Female mosquitoes require a blood meal for reproduction, and this blood meal
      provides the underlying mechanism for the spread of many important vector-borne
      diseases in humans. A deeper understanding of the molecular mechanisms linked to
      mosquito blood meal processes and reproductive events is of particular importance
      for devising innovative vector control strategies. We found that the conserved
      microRNA miR-8 is an essential regulator of mosquito reproductive events. Two
      strategies to inhibit miR-8 function in vivo were used for functional
      characterization: systemic antagomir depletion and spatiotemporal inhibition
      using the miRNA sponge transgenic method in combination with the yeast
      transcriptional activator gal4 protein/upstream activating sequence system.
      Depletion of miR-8 in the female mosquito results in defects related to egg
      development and deposition. We used a multialgorithm approach for miRNA target
      prediction in mosquito 3' UTRs and experimentally verified secreted wingless
      interacting molecule (swim) as an authentic target of miR-8. Our findings
      demonstrate that miR-8 controls the activity of the long-range Wingless (Wg)
      signaling by regulating Swim expression in the female fat body. We discovered
      that the miR-8/Wg axis is critical for the proper secretion of lipophorin and
      vitellogenin by the fat body and subsequent accumulation of these yolk protein
      precursors by developing oocytes. 

PMID- 25605934
TI  - Direct laser manipulation reveals the mechanics of cell contacts in vivo.
AB  - Cell-generated forces produce a variety of tissue movements and tissue shape
      changes. The cytoskeletal elements that underlie these dynamics act at cell-cell
      and cell-ECM contacts to apply local forces on adhesive structures. In epithelia,
      force imbalance at cell contacts induces cell shape changes, such as apical
      constriction or polarized junction remodeling, driving tissue morphogenesis. The
      dynamics of these processes are well-characterized; however, the mechanical basis
      of cell shape changes is largely unknown because of a lack of mechanical
      measurements in vivo. We have developed an approach combining optical tweezers
      with light-sheet microscopy to probe the mechanical properties of epithelial cell
      junctions in the early Drosophila embryo. We show that optical trapping can
      efficiently deform cell-cell interfaces and measure tension at cell junctions,
      which is on the order of 100 pN. We show that tension at cell junctions
      equilibrates over a few seconds, a short timescale compared with the contractile
      events that drive morphogenetic movements. We also show that tension increases
      along cell interfaces during early tissue morphogenesis and becomes anisotropic
      as cells intercalate during germ-band extension. By performing pull-and-release
      experiments, we identify time-dependent properties of junctional mechanics
      consistent with a simple viscoelastic model. Integrating this constitutive law
      into a tissue-scale model, we predict quantitatively how local deformations
      propagate throughout the tissue. 

PMID- 25605935
TI  - Structure, variation, and assembly of the root-associated microbiomes of rice.
AB  - Plants depend upon beneficial interactions between roots and microbes for
      nutrient availability, growth promotion, and disease suppression. High-throughput
      sequencing approaches have provided recent insights into root microbiomes, but
      our current understanding is still limited relative to animal microbiomes. Here
      we present a detailed characterization of the root-associated microbiomes of the
      crop plant rice by deep sequencing, using plants grown under controlled
      conditions as well as field cultivation at multiple sites. The spatial resolution
      of the study distinguished three root-associated compartments, the endosphere
      (root interior), rhizoplane (root surface), and rhizosphere (soil close to the
      root surface), each of which was found to harbor a distinct microbiome. Under
      controlled greenhouse conditions, microbiome composition varied with soil source
      and genotype. In field conditions, geographical location and cultivation
      practice, namely organic vs. conventional, were factors contributing to
      microbiome variation. Rice cultivation is a major source of global methane
      emissions, and methanogenic archaea could be detected in all spatial compartments
      of field-grown rice. The depth and scale of this study were used to build
      coabundance networks that revealed potential microbial consortia, some of which
      were involved in methane cycling. Dynamic changes observed during microbiome
      acquisition, as well as steady-state compositions of spatial compartments,
      support a multistep model for root microbiome assembly from soil wherein the
      rhizoplane plays a selective gating role. Similarities in the distribution of
      phyla in the root microbiomes of rice and other plants suggest that conclusions
      derived from this study might be generally applicable to land plants. 

PMID- 25605936
TI  - Jagged-Delta asymmetry in Notch signaling can give rise to a Sender/Receiver
      hybrid phenotype.
AB  - Notch signaling pathway mediates cell-fate determination during embryonic
      development, wound healing, and tumorigenesis. This pathway is activated when the
      ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor
      of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that
      activates many downstream target genes. NICD affects ligand production
      asymmetrically--it represses Delta, but activates Jagged. Although the dynamical
      role of Notch-Jagged signaling remains elusive, it is widely recognized that
      Notch-Delta signaling behaves as an intercellular toggle switch, giving rise to
      two distinct fates that neighboring cells adopt--Sender (high ligand, low
      receptor) and Receiver (low ligand, high receptor). Here, we devise a specific
      theoretical framework that incorporates both Delta and Jagged in Notch signaling
      circuit to explore the functional role of Jagged in cell-fate determination. We
      find that the asymmetric effect of NICD renders the circuit to behave as a three
      way switch, giving rise to an additional state--a hybrid Sender/Receiver (medium
      ligand, medium receptor). This phenotype allows neighboring cells to both send
      and receive signals, thereby attaining similar fates. We also show that due to
      the asymmetric effect of the glycosyltransferase Fringe, different outcomes are
      generated depending on which ligand is dominant: Delta-mediated signaling drives
      neighboring cells to have an opposite fate; Jagged-mediated signaling drives the
      cell to maintain a similar fate to that of its neighbor. We elucidate the role of
      Jagged in cell-fate determination and discuss its possible implications in
      understanding tumor-stroma cross-talk, which frequently entails Notch-Jagged
      communication. 

PMID- 25605937
TI  - Osteocytes mediate the anabolic actions of canonical Wnt/beta-catenin signaling
      in bone.
AB  - Osteocytes, >90% of the cells in bone, lie embedded within the mineralized matrix
      and coordinate osteoclast and osteoblast activity on bone surfaces by mechanisms
      still unclear. Bone anabolic stimuli activate Wnt signaling, and human mutations
      of components along this pathway underscore its crucial role in bone accrual and
      maintenance. However, the cell responsible for orchestrating Wnt anabolic actions
      has remained elusive. We show herein that activation of canonical Wnt signaling
      exclusively in osteocytes [dominant active (da)betacat(Ot) mice] induces bone
      anabolism and triggers Notch signaling without affecting survival. These features
      contrast with those of mice expressing the same dabeta-catenin in osteoblasts,
      which exhibit decreased resorption and perinatal death from leukemia.
      dabetacat(Ot) mice exhibit increased bone mineral density in the axial and
      appendicular skeleton, and marked increase in bone volume in
      cancellous/trabecular and cortical compartments compared with littermate
      controls. dabetacat(Ot) mice display increased resorption and formation markers,
      high number of osteoclasts and osteoblasts in cancellous and cortical bone,
      increased bone matrix production, and markedly elevated periosteal bone formation
      rate. Wnt and Notch signaling target genes, osteoblast and osteocyte markers, and
      proosteoclastogenic and antiosteoclastogenic cytokines are elevated in bones of
      dabetacat(Ot) mice. Further, the increase in RANKL depends on Sost/sclerostin.
      Thus, activation of osteocytic beta-catenin signaling increases both osteoclasts
      and osteoblasts, leading to bone gain, and is sufficient to activate the Notch
      pathway. These findings demonstrate disparate outcomes of beta-catenin activation
      in osteocytes versus osteoblasts and identify osteocytes as central target cells
      of the anabolic actions of canonical Wnt/beta-catenin signaling in bone. 

PMID- 25605938
TI  - TFIIH-dependent MMP-1 overexpression in trichothiodystrophy leads to
      extracellular matrix alterations in patient skin.
AB  - Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result
      in distinct clinical entities, including the cancer-prone xeroderma pigmentosum
      (XP) and the multisystem disorder trichothiodystrophy (TTD), which share only
      cutaneous photosensitivity. Gene-expression profiles of primary dermal
      fibroblasts revealed overexpression of matrix metalloproteinase 1 (MMP-1), the
      gene encoding the metalloproteinase that degrades the interstitial collagens of
      the extracellular matrix (ECM), in TTD patients mutated in XPD compared with
      their healthy parents. The defect is observed in TTD and not in XP and is
      specific for fibroblasts, which are the main producers of dermal ECM. MMP-1
      transcriptional up-regulation in TTD is caused by an erroneous signaling mediated
      by retinoic acid receptors on the MMP-1 promoter and leads to hypersecretion of
      active MMP-1 enzyme and degradation of collagen type I in the ECM of cell/tissue
      systems and TTD patient skin. In agreement with the well-known role of ECM in
      eliciting signaling events controlling cell behavior and tissue homeostasis, ECM
      alterations in TTD were shown to impact on the migration and wound-healing
      properties of patient dermal fibroblasts. The presence of a specific inhibitor of
      MMP activity was sufficient to restore normal cell migration, thus providing a
      potential approach for therapeutic strategies. This study highlights the
      relevance of ECM anomalies in TTD pathogenesis and in the phenotypic differences
      between TTD and XP. 

PMID- 25605939
TI  - Flagellin-induced NLRC4 phosphorylation primes the inflammasome for activation by
      NAIP5.
AB  - The Nlrc4 inflammasome contributes to immunity against intracellular pathogens
      that express flagellin and type III secretion systems, and activating mutations
      in NLRC4 cause autoinflammation in patients. Both Naip5 and phosphorylation of
      Nlrc4 at Ser533 are required for flagellin-induced inflammasome activation, but
      how these events converge upon inflammasome activation is not known. Here, we
      showed that Nlrc4 phosphorylation occurs independently of Naip5 detection of
      flagellin because Naip5 deletion in macrophages abolished caspase-1 activation,
      interleukin (IL)-1beta secretion, and pyroptosis, but not Nlrc4 phosphorylation
      by cytosolic flagellin of Salmonella Typhimurium and Yersinia enterocolitica. ASC
      speck formation and caspase-1 expression also were dispensable for Nlrc4
      phosphorylation. Interestingly, Helicobacter pylori flagellin triggered robust
      Nlrc4 phosphorylation, but failed to elicit caspase-1 maturation, IL-1beta
      secretion, and pyroptosis, suggesting that it retained Nlrc4 Ser533
      phosphorylating-activity despite escaping Naip5 detection. In agreement, the
      flagellin D0 domain was required and sufficient for Nlrc4 phosphorylation,
      whereas deletion of the S. Typhimurium flagellin carboxy-terminus prevented
      caspase-1 maturation only. Collectively, this work suggests a biphasic activation
      mechanism for the Nlrc4 inflammasome in which Ser533 phosphorylation prepares
      Nlrc4 for subsequent activation by the flagellin sensor Naip5. 

PMID- 25605940
TI  - MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma
      cells.
AB  - Canonical Wnt signaling plays an important role in development and disease,
      regulating transcription of target genes and stabilizing many proteins
      phosphorylated by glycogen synthase kinase 3 (GSK3). We observed that the MiT
      family of transcription factors, which includes the melanoma oncogene MITF
      (micropthalmia-associated transcription factor) and the lysosomal master
      regulator TFEB, had the highest phylogenetic conservation of three consecutive
      putative GSK3 phosphorylation sites in animal proteomes. This finding prompted us
      to examine the relationship between MITF, endolysosomal biogenesis, and Wnt
      signaling. Here we report that MITF expression levels correlated with the
      expression of a large subset of lysosomal genes in melanoma cell lines. MITF
      expression in the tetracycline-inducible C32 melanoma model caused a marked
      increase in vesicular structures, and increased expression of late endosomal
      proteins, such as Rab7, LAMP1, and CD63. These late endosomes were not functional
      lysosomes as they were less active in proteolysis, yet were able to concentrate
      Axin1, phospho-LRP6, phospho-beta-catenin, and GSK3 in the presence of Wnt
      ligands. This relocalization significantly enhanced Wnt signaling by increasing
      the number of multivesicular bodies into which the Wnt signalosome/destruction
      complex becomes localized upon Wnt signaling. We also show that the MITF protein
      was stabilized by Wnt signaling, through the novel C-terminal GSK3
      phosphorylations identified here. MITF stabilization caused an increase in
      multivesicular body biosynthesis, which in turn increased Wnt signaling,
      generating a positive-feedback loop that may function during the proliferative
      stages of melanoma. The results underscore the importance of misregulated
      endolysosomal biogenesis in Wnt signaling and cancer. 

PMID- 25605942
TI  - Short time interval for condensation of high-temperature silicates in the solar
      accretion disk.
AB  - Chondritic meteorites are made of primitive components that record the first
      steps of formation of solids in our Solar System. Chondrules are the major
      component of chondrites, yet little is known about their formation mechanisms and
      history within the solar protoplanetary disk (SPD). We use the reconstructed
      concentrations of short-lived (26)Al in chondrules to constrain the timing of
      formation of their precursors in the SPD. High-precision bulk magnesium isotopic
      measurements of 14 chondrules from the Allende chondrite define a (26)Al isochron
      with (26)Al/(27)Al = 1.2(+/-0.2) * 10(-5) for this subset of Allende chondrules.
      This can be considered to be the minimum bulk chondrule (26)Al isochron because
      all chondrules analyzed so far with high precision (~50 chondrules from CV and
      ordinary chondrites) have an inferred minimum bulk initial ((26)Al/(27)Al) >= 1.2
      * 10(-5). In addition, mineral (26)Al isochrons determined on the same chondrules
      show that their formation (i.e., fusion of their precursors by energetic events)
      took place from 0 Myr to ~2 Myr after the formation of their precursors, thus
      showing in some cases a clear decoupling in time between the two events. The
      finding of a minimum bulk chondrule (26)Al isochron is used to constrain the
      astrophysical settings for chondrule formation. Either the temperature of the
      condensation zone dropped below the condensation temperature of chondrule
      precursors at ~1.5 My after the start of the Solar System or the transport of
      precursors from the condensation zone to potential storage sites stopped after
      1.5 My, possibly due to a drop in the disk accretion rate. 

PMID- 25605941
TI  - Ventral striatal dopamine reflects behavioral and neural signatures of model
      based control during sequential decision making.
AB  - Dual system theories suggest that behavioral control is parsed between a
      deliberative "model-based" and a more reflexive "model-free" system. A balance of
      control exerted by these systems is thought to be related to dopamine
      neurotransmission. However, in the absence of direct measures of human dopamine,
      it remains unknown whether this reflects a quantitative relation with dopamine
      either in the striatum or other brain areas. Using a sequential decision task
      performed during functional magnetic resonance imaging, combined with striatal
      measures of dopamine using [(18)F]DOPA positron emission tomography, we show that
      higher presynaptic ventral striatal dopamine levels were associated with a
      behavioral bias toward more model-based control. Higher presynaptic dopamine in
      ventral striatum was associated with greater coding of model-based signatures in
      lateral prefrontal cortex and diminished coding of model-free prediction errors
      in ventral striatum. Thus, interindividual variability in ventral striatal
      presynaptic dopamine reflects a balance in the behavioral expression and the
      neural signatures of model-free and model-based control. Our data provide a novel
      perspective on how alterations in presynaptic dopamine levels might be
      accompanied by a disruption of behavioral control as observed in aging or
      neuropsychiatric diseases such as schizophrenia and addiction. 

PMID- 25605943
TI  - Clonal analysis reveals a common origin between nonsomite-derived neck muscles
      and heart myocardium.
AB  - Neck muscles constitute a transition zone between somite-derived skeletal muscles
      of the trunk and limbs, and muscles of the head, which derive from cranial
      mesoderm. The trapezius and sternocleidomastoid neck muscles are formed from
      progenitor cells that have expressed markers of cranial pharyngeal mesoderm,
      whereas other muscles in the neck arise from Pax3-expressing cells in the
      somites. Mef2c-AHF-Cre genetic tracing experiments and Tbx1 mutant analysis show
      that nonsomitic neck muscles share a gene regulatory network with cardiac
      progenitor cells in pharyngeal mesoderm of the second heart field (SHF) and
      branchial arch-derived head muscles. Retrospective clonal analysis shows that
      this group of neck muscles includes laryngeal muscles and a component of the
      splenius muscle, of mixed somitic and nonsomitic origin. We demonstrate that the
      trapezius muscle group is clonally related to myocardium at the venous pole of
      the heart, which derives from the posterior SHF. The left clonal sublineage
      includes myocardium of the pulmonary trunk at the arterial pole of the heart.
      Although muscles derived from the first and second branchial arches also share a
      clonal relationship with different SHF-derived parts of the heart, neck muscles
      are clonally distinct from these muscles and define a third clonal population of
      common skeletal and cardiac muscle progenitor cells within cardiopharyngeal
      mesoderm. By linking neck muscle and heart development, our findings highlight
      the importance of cardiopharyngeal mesoderm in the evolution of the vertebrate
      heart and neck and in the pathophysiology of human congenital disease. 

PMID- 25605944
TI  - Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program.
AB  - Substantial evidence supports the hypothesis that enhancers are critical
      regulators of cell-type determination, orchestrating both positive and negative
      transcriptional programs; however, the basic mechanisms by which enhancers
      orchestrate interactions with cognate promoters during activation and repression
      events remain incompletely understood. Here we report the required actions of LIM
      domain-binding protein 1 (LDB1)/cofactor of LIM homeodomain protein 2/nuclear LIM
      interactor, interacting with the enhancer-binding protein achaete-scute complex
      homolog 1, to mediate looping to target gene promoters and target gene regulation
      in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be
      required for both activation and repression of these target genes. Although LDB1
      dependent activated genes are regulated at the level of transcriptional
      initiation, the LDB1-dependent repressed transcription units appear to be
      regulated primarily at the level of promoter pausing, with LDB1 regulating
      recruitment of metastasis-associated 1 family, member 2, a component of the
      nucleosome remodeling deacetylase complex, on these negative enhancers, required
      for the repressive enhancer function. These results indicate that LDB1-dependent
      looping events can deliver repressive cargo to cognate promoters to mediate
      promoter pausing events in a pituitary cell type. 

PMID- 25605945
TI  - The first step of peptide selection in antigen presentation by MHC class I
      molecules.
AB  - MHC class I molecules present a variable but limited repertoire of antigenic
      peptides for T-cell recognition. Understanding how peptide selection is achieved
      requires mechanistic insights into the interactions between the MHC I and
      candidate peptides. We find that, at first encounter, MHC I H-2K(b) considers a
      wide range of peptides, including those with expanded N termini and unfitting
      anchor residues. Discrimination occurs in the second step, when noncanonical
      peptides dissociate with faster exchange rates. This second step exhibits
      remarkable temperature sensitivity, as illustrated by numerous noncanonical
      peptides presented by H-2K(b) in cells cultured at 26  degrees C relative to 37 
      degrees C. Crystallographic analyses of H-2K(b)-peptide complexes suggest that a
      conformational adaptation of H-2K(b) drives the decisive step in peptide
      selection. We propose that MHC class I molecules consider initially a large
      peptide pool, subsequently refined by a temperature-sensitive induced-fit
      mechanism to retain the canonical peptide repertoire. 

PMID- 25605946
TI  - Low spatial coherence electrically pumped semiconductor laser for speckle-free
      full-field imaging.
AB  - The spatial coherence of laser sources has limited their application to parallel
      imaging and projection due to coherent artifacts, such as speckle. In contrast,
      traditional incoherent light sources, such as thermal sources or light emitting
      diodes (LEDs), provide relatively low power per independent spatial mode. Here,
      we present a chip-scale, electrically pumped semiconductor laser based on a novel
      design, demonstrating high power per mode with much lower spatial coherence than
      conventional laser sources. The laser resonator was fabricated with a chaotic, D
      shaped cavity optimized to achieve highly multimode lasing. Lasing occurs
      simultaneously and independently in ~1,000 modes, and hence the total emission
      exhibits very low spatial coherence. Speckle-free full-field imaging is
      demonstrated using the chaotic cavity laser as the illumination source. The power
      per mode of the sample illumination is several orders of magnitude higher than
      that of a LED or thermal light source. Such a compact, low-cost source, which
      combines the low spatial coherence of a LED with the high spectral radiance of a
      laser, could enable a wide range of high-speed, full-field imaging and projection
      applications. 

PMID- 25605947
TI  - Imaging Dirac-mass disorder from magnetic dopant atoms in the ferromagnetic
      topological insulator Crx(Bi0.1Sb0.9)2-xTe3.
AB  - To achieve and use the most exotic electronic phenomena predicted for the surface
      states of 3D topological insulators (TIs), it is necessary to open a "Dirac-mass
      gap" in their spectrum by breaking time-reversal symmetry. Use of magnetic dopant
      atoms to generate a ferromagnetic state is the most widely applied approach.
      However, it is unknown how the spatial arrangements of the magnetic dopant atoms
      influence the Dirac-mass gap at the atomic scale or, conversely, whether the
      ferromagnetic interactions between dopant atoms are influenced by the topological
      surface states. Here we image the locations of the magnetic (Cr) dopant atoms in
      the ferromagnetic TI Cr0.08(Bi0.1Sb0.9)1.92Te3. Simultaneous visualization of the
      Dirac-mass gap Delta(r) reveals its intense disorder, which we demonstrate is
      directly related to fluctuations in n(r), the Cr atom areal density in the
      termination layer. We find the relationship of surface-state Fermi wavevectors to
      the anisotropic structure of Delta(r) not inconsistent with predictions for
      surface ferromagnetism mediated by those states. Moreover, despite the intense
      Dirac-mass disorder, the anticipated relationship [Formula: see text] is
      confirmed throughout and exhibits an electron-dopant interaction energy J* = 145
      meV.nm(2). These observations reveal how magnetic dopant atoms actually generate
      the TI mass gap locally and that, to achieve the novel physics expected of time
      reversal symmetry breaking TI materials, control of the resulting Dirac-mass gap
      disorder will be essential. 

PMID- 25605949
TI  - Multifocal tuberculous osteomyelitis.

PMID- 25605948
TI  - Genetic engineering of hematopoietic stem cells to generate invariant natural
      killer T cells.
AB  - Invariant natural killer T (iNKT) cells comprise a small population of alphabeta
      T lymphocytes. They bridge the innate and adaptive immune systems and mediate
      strong and rapid responses to many diseases, including cancer, infections,
      allergies, and autoimmunity. However, the study of iNKT cell biology and the
      therapeutic applications of these cells are greatly limited by their small
      numbers in vivo (~0.01-1% in mouse and human blood). Here, we report a new method
      to generate large numbers of iNKT cells in mice through T-cell receptor (TCR)
      gene engineering of hematopoietic stem cells (HSCs). We showed that iNKT TCR
      engineered HSCs could generate a clonal population of iNKT cells. These HSC
      engineered iNKT cells displayed the typical iNKT cell phenotype and
      functionality. They followed a two-stage developmental path, first in thymus and
      then in the periphery, resembling that of endogenous iNKT cells. When tested in a
      mouse melanoma lung metastasis model, the HSC-engineered iNKT cells effectively
      protected mice from tumor metastasis. This method provides a powerful and high
      throughput tool to investigate the in vivo development and functionality of
      clonal iNKT cells in mice. More importantly, this method takes advantage of the
      self-renewal and longevity of HSCs to generate a long-term supply of engineered
      iNKT cells, thus opening up a new avenue for iNKT cell-based immunotherapy. 

PMID- 25605950
TI  - Spinal cord tumour misdiagnosed as seropositive neuromyelitis optica spectrum
      disorder.

PMID- 25605951
TI  - Improvement and evaluation.

PMID- 25605952
TI  - What is a performance outlier?

PMID- 25605953
TI  - Self-reported patient safety competence among Canadian medical students and
      postgraduate trainees: a cross-sectional survey.
AB  - BACKGROUND: Quality and patient safety (PS) are critical components of medical
      education. This study reports on the self-reported PS competence of medical
      students and postgraduate trainees. METHODS: The Health Professional Education in
      Patient Safety Survey was administered to medical students and postgraduate
      trainees in January 2012. PS dimension scores were compared across learning
      settings (classroom and clinical) and year in programme. RESULTS: Sixty-three
      percent (255/406) of medical students and 32% (141/436) of postgraduate trainees
      responded. In general, both groups were most confident in their learning of
      clinical safety skills (eg, hand hygiene) and least confident in learning about
      sociocultural aspects of safety (eg, understanding human factors). Medical
      students' confidence in most aspects of safety improved with years of training.
      For some of the more intangible dimensions (teamwork and culture), medical
      students in their final year had lower scores than students in earlier years.
      Thirty-eight percent of medical students felt they could approach someone
      engaging in unsafe practice, and the majority of medical students (85%) and
      postgraduate trainees (78%) agreed it was difficult to question authority.
      CONCLUSIONS: Our results suggest the need to improve the overall content,
      structure and integration of PS concepts in both classroom and clinical learning
      environments. Decreased confidence in sociocultural aspects of PS among medical
      students in the final year of training may indicate that culture in clinical
      settings negatively affects students' perceived PS competence. Alternatively, as
      medical students spend more time in the clinical setting, they may develop a
      clearer sense of what they do not know.

PMID- 25605954
TI  - Confounding explains 'deaths avoided'.

PMID- 25605955
TI  - Measuring the true impact of an electronic physiological surveillance system
      (EPSS).

PMID- 25605956
TI  - Impact of introducing an electronic physiological surveillance system on hospital
      mortality.

PMID- 25605957
TI  - Influence of different interfaces on synchrony during pressure support
      ventilation in a pediatric setting: a bench study.
AB  - BACKGROUND: In adults and children, patient-ventilator synchrony is strongly
      dependent on both the ventilator settings and interface used in applying positive
      pressure to the airway. The aim of this bench study was to determine whether
      different interfaces and ventilator settings may influence patient-ventilator
      interaction in pediatric models of normal and mixed obstructive and restrictive
      respiratory conditions. METHODS: A test lung, connected to a pediatric mannequin
      using different interfaces (endotracheal tube [ETT], face mask, and helmet), was
      ventilated in pressure support ventilation mode testing 2 ventilator settings
      (pressurization time [Timepress]50%/cycling-off flow threshold [Trexp]25%,
      Timepress80%/Trexp60%), randomly applied. The test lung was set to simulate one
      pediatric patient with a healthy respiratory system and another with a mixed
      obstructive and restricted respiratory condition, at different breathing
      frequencies (f) (30, 40, and 50 breaths/min). We measured inspiratory trigger
      delay, pressurization time, expiratory trigger delay, and time of synchrony.
      RESULTS: At each breathing frequency, the helmet showed the longest inspiratory
      trigger delay compared with the ETT and face mask. At f30, the ETT had a reduced
      Tpress. The helmet had the shortest Tpress in the simulated child with a mixed
      obstructive and restricted respiratory condition, at f40 during
      Timepress50%/Trexp25% and at f50 during Timepress80%/Trexp60%. In the simulated
      child with a normal respiratory condition, the ETT presented the shortest Tpress
      value at f50 during Timepress80%/Trexp60%. Concerning the expiratory trigger
      delay, the helmet showed the best interaction at f30, but the worst at f40 and at
      f50. The helmet showed the shortest time of synchrony during all ventilator
      settings. CONCLUSIONS: The choice of the interface can influence patient
      ventilator synchrony in a pediatric model breathing at increased f, thus making
      it more difficult to set the ventilator, particularly during noninvasive
      ventilation. The helmet demonstrated the worst interaction, suggesting that the
      face mask should be considered as the first choice for delivering noninvasive
      ventilation in a pediatric model.

PMID- 25605958
TI  - Additional Evidence for the Long-Term Benefits of Pulmonary Rehabilitation.
AB  - BACKGROUND: Pulmonary rehabilitation programs document outcomes to prepare for
      program certification, to demonstrate the value of the program to upper
      management, and to provide feedback to pulmonary rehabilitation staff regarding
      the efficacy of the program. The overall goal of this study was to evaluate the
      feasibility of using non-research-generated clinical data to report long-term
      outcomes following a pulmonary rehabilitation program. METHODS: Using a
      longitudinal descriptive design, all subjects who completed pulmonary
      rehabilitation at one community-based pulmonary rehabilitation program in the San
      Francisco Bay Area were asked to complete a 6-month and subsequent yearly
      questionnaires. Adherence to pulmonary rehabilitation techniques was described
      for 7 y following pulmonary rehabilitation participation, health-care utilization
      from 1 y before pulmonary rehabilitation was compared with subsequent years, and
      health-care utilization was compared between those who participated in ongoing
      regular exercise after pulmonary rehabilitation and those who did not exercise.
      RESULTS: More than 70% of subjects who completed the questionnaire reported
      adherence to pulmonary rehabilitation techniques, including exercise for at least
      7 y following pulmonary rehabilitation. Health-care utilization declined after
      pulmonary rehabilitation. Subjects who did not exercise regularly required
      significantly more health care than those who exercised regularly (P < .05).
      CONCLUSIONS: This study demonstrated the ability of one pulmonary rehabilitation
      program to accurately monitor extended long-term follow-up after pulmonary
      rehabilitation. Implementing this long-term monitoring methodology consistently
      in pulmonary rehabilitation programs could contribute to evaluation of the
      comparative effectiveness of various treatment options.

PMID- 25605959
TI  - Subcutaneous Emphysema in Acute Asthma: A Cause for Concern?
AB  - Pneumomediastinum has been described in patients with asthma. In this case
      report, we describe a young patient who presented to our medical assessment unit
      with an asthma exacerbation and progressive dyspnea. The patient developed
      pneumomediastinum, a rare complication of an asthma exacerbation.
      Pneumomediastinum is usually characterized by chest pain, dyspnea, and neck
      swelling caused by subcutaneous emphysema. Although the condition is usually
      benign and treatment is primarily supportive, surgical intervention may be needed
      if the patient develops hemodynamic compromise or respiratory failure through
      mechanisms similar to those seen in a tension pneumothorax. 

PMID- 25605960
TI  - atBRX1-1 and atBRX1-2 are involved in an alternative rRNA processing pathway in
      Arabidopsis thaliana.
AB  - Ribosome biogenesis is an essential process in all organisms. In eukaryotes,
      multiple ribosome biogenesis factors (RBFs) act in the processing of ribosomal
      (r)RNAs, assembly of ribosomal subunits and their export to the cytoplasm. We
      characterized two genes in Arabidopsis thaliana coding for orthologs of yeast
      BRX1, a protein involved in maturation of the large ribosomal subunit. Both
      atBRX1 proteins, encoded by AT3G15460 and AT1G52930, respectively, are mainly
      localized in the nucleolus and are ubiquitously expressed throughout plant
      development and in various tissues. Mutant plant lines for both factors show a
      delay in development and pointed leaves can be observed in the brx1-2 mutant,
      implying a link between ribosome biogenesis and plant development. In addition,
      the pre-rRNA processing is affected in both mutants. Analysis of the pre-rRNA
      intermediates revealed that early processing steps can occur either in the 5'
      external transcribed spacer (ETS) or internal transcribed spacer 1 (ITS1).
      Interestingly, we also find that in xrn2 mutants, early processing events can be
      bypassed and removal of the 5' ETS is initiated by cleavage at the P' processing
      site. While the pathways of pre-rRNA processing are comparable to those of yeast
      and mammalian cells, the balance between the two processing pathways is different
      in plants. Furthermore, plant-specific steps such as an additional processing
      site in the 5' ETS, likely post-transcriptional processing of the early cleavage
      sites and accumulation of a 5' extended 5.8S rRNA not observed in other
      eukaryotes can be detected. 

PMID- 25605961
TI  - Evolutionary conservation of a molecular machinery for export and expression of
      mRNAs with retained introns.
AB  - Intron retention is one of the least studied forms of alternative splicing.
      Through the use of retrovirus and other model systems, it was established many
      years ago that mRNAs with retained introns are subject to restriction both at the
      level of nucleocytoplasmic export and cytoplasmic expression. It was also
      demonstrated that specific cis-acting elements in the mRNA could serve to bypass
      these restrictions. Here we show that one of these elements, the constitutive
      transport element (CTE), first identified in the retrovirus MPMV and subsequently
      in the human NXF1 gene, is a highly conserved element. Using GERP analysis, CTEs
      with strong primary sequence homology, predicted to display identical secondary
      structure, were identified in NXF genes from >30 mammalian species. CTEs were
      also identified in the predicted NXF1 genes of zebrafish and coelacanths. The CTE
      from the zebrafish NXF1 was shown to function efficiently to achieve expression
      of mRNA with a retained intron in human cells in conjunction with zebrafish Nxf1
      and cofactor Nxt proteins. This demonstrates that all essential functional
      components for expression of mRNA with retained introns have been conserved from
      fish to man. 

PMID- 25605963
TI  - Using droplet-based microfluidics to improve the catalytic properties of RNA
      under multiple-turnover conditions.
AB  - In vitro evolution methodologies are powerful approaches to identify RNA with new
      functionalities. While Systematic Evolution of Ligands by Exponential enrichment
      (SELEX) is an efficient approach to generate new RNA aptamers, it is less suited
      for the isolation of efficient ribozymes as it does not select directly for the
      catalysis. In vitro compartmentalization (IVC) in aqueous droplets in emulsions
      allows catalytic RNAs to be selected under multiple-turnover conditions but
      suffers severe limitations that can be overcome using the droplet-based
      microfluidics workflow described in this paper. Using microfluidics, millions of
      genes in a library can be individually compartmentalized in highly monodisperse
      aqueous droplets and serial operations performed on them. This allows the
      different steps of the evolution process (gene amplification, transcription, and
      phenotypic assay) to be uncoupled, making the method highly flexible, applicable
      to the selection and evolution of a variety of RNAs, and easily adaptable for
      evolution of DNA or proteins. To demonstrate the method, we performed cycles of
      random mutagenesis and selection to evolve the X-motif, a ribozyme which, like
      many ribozymes selected using SELEX, has limited multiple-turnover activity. This
      led to the selection of variants, likely to be the optimal ribozymes that can be
      generated using point mutagenesis alone, with a turnover number under multiple
      turnover conditions, k(ss) cat, ~ 28-fold higher than the original X-motif,
      primarily due to an increase in the rate of product release, the rate-limiting
      step in the multiple-turnover reaction.

PMID- 25605962
TI  - Arginine methylation and citrullination of splicing factor proline- and glutamine
      rich (SFPQ/PSF) regulates its association with mRNA.
AB  - Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as
      polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its
      binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb),
      are highly abundant, multifunctional nuclear proteins. However, the exact role of
      this complex is yet to be determined. Following purification of the endogeneous
      SFPQ/NONO complex, mass spectrometry analysis identified a wide range of
      interacting proteins, including those involved in RNA processing, RNA splicing,
      and transcriptional regulation, consistent with a multifunctional role for
      SFPQ/NONO. In addition, we have identified several sites of arginine methylation
      in SFPQ/PSF using mass spectrometry and found that several arginines in the N
      terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find
      that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation
      in vitro and that this is antagonized by citrullination of SFPQ. Arginine
      methylation and citrullination of SFPQ/PSF does not affect complex formation with
      NONO. However, arginine methylation was shown to increase the association with
      mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical
      properties of the endogenous complex from cell lysates are significantly
      influenced by the ionic strength during purification. At low ionic strength, the
      SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates,
      preventing the purification of the SFPQ/NONO complex. The ability of the
      SFPQ/NONO complex to form varying protein assemblies, in conjunction with the
      effect of post-translational modifications of SFPQ modulating mRNA binding,
      suggests key roles affecting mRNP dynamics within the cell. 

PMID- 25605964
TI  - Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and
      U2AF65 and modulates alternative pre-mRNA splicing in vivo.
AB  - The first stable complex formed during the assembly of spliceosomes onto pre-mRNA
      substrates in mammals includes U1 snRNP, which recognizes the 5' splice site, and
      the splicing factors SF1 and U2AF, which bind the branch point sequence,
      polypyrimidine tract, and 3' splice site. The 5' and 3' splice site complexes are
      thought to be joined together by protein-protein interactions mediated by factors
      that ensure the fidelity of the initial splice site recognition. In this study,
      we identified and characterized PRPF40B, a putative mammalian ortholog of the U1
      snRNP-associated yeast splicing factor Prp40. PRPF40B is highly enriched in
      speckles with a behavior similar to splicing factors. We demonstrated that
      PRPF40B interacts directly with SF1 and associates with U2AF(65). Accordingly,
      PRPF40B colocalizes with these splicing factors in the cell nucleus. Splicing
      assays with reporter minigenes revealed that PRPF40B modulates alternative splice
      site selection. In the case of Fas regulation of alternative splicing, weak 5'
      and 3' splice sites and exonic sequences are required for PRPF40B function.
      Placing our data in a functional context, we also show that PRPF40B depletion
      increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability
      of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate
      cell survival. 

PMID- 25605965
TI  - A deeply conserved, noncanonical miRNA hosted by ribosomal DNA.
AB  - Advances in small RNA sequencing technologies and comparative genomics have
      fueled comprehensive microRNA (miRNA) gene annotations in humans and model
      organisms. Although new miRNAs continue to be discovered in recent years, these
      have universally been lowly expressed, recently evolved, and of debatable
      endogenous activity, leading to the general assumption that virtually all
      biologically important miRNAs have been identified. Here, we analyzed small RNAs
      that emanate from the highly repetitive rDNA arrays of Drosophila. In addition to
      endo-siRNAs derived from sense and antisense strands of the pre-rRNA sequence, we
      unexpectedly identified a novel, deeply conserved, noncanonical miRNA. Although
      this miRNA is widely expressed, this miRNA was not identified by previous studies
      due to bioinformatics filters removing such repetitive sequences. Deep-sequencing
      data provide clear evidence for specific processing with precisely defined 5' and
      3' ends. Furthermore, we demonstrate that the mature miRNA species is
      incorporated in the effector complexes and has detectable trans regulatory
      activity. Processing of this miRNA requires Dicer-1, whereas the Drosha-Pasha
      complex is dispensable. The miRNA hairpin sequence is located in the internal
      transcribed spacer 1 region of rDNA and is highly conserved among Dipteran
      species that were separated from their common ancestor ~ 100 million years ago.
      Our results suggest that biologically active miRNA genes may remain unidentified
      even in well-studied organisms.

PMID- 25605966
TI  - Social network diversity and white matter microstructural integrity in humans.
AB  - Diverse aspects of physical, affective and cognitive health relate to social
      integration, reflecting engagement in social activities and identification with
      diverse roles within a social network. However, the mechanisms by which social
      integration interacts with the brain are unclear. In healthy adults (N = 155), we
      tested the links between social integration and measures of white matter
      microstructure using diffusion tensor imaging. Across the brain, there was a
      predominantly positive association between a measure of white matter integrity,
      fractional anisotropy (FA), and social network diversity. This association was
      particularly strong in a region near the anterior corpus callosum and driven by a
      negative association with the radial component of the diffusion signal. This
      callosal region contained projections between bilateral prefrontal cortices, as
      well as cingulum and corticostriatal pathways. FA within this region was weakly
      associated with circulating levels of the inflammatory cytokine interleukin-6 (IL
      6), but IL-6 did not mediate the social network and FA relationship. Finally,
      variation in FA indirectly mediated the relationship between social network
      diversity and intrinsic functional connectivity of medial corticostriatal
      pathways. These findings suggest that social integration relates to myelin
      integrity in humans, which may help explain the diverse aspects of health
      affected by social networks. 

PMID- 25605967
TI  - Loving yourself more than your neighbor: ERPs reveal online effects of a self
      positivity bias.
AB  - A large body of social psychological research suggests that we think quite
      positively of ourselves, often unrealistically so. Research on this 'self
      positivity bias' has relied mainly on self-report and behavioral measures, but
      these can suffer from a number of problems including confounds that arise from
      the desire to present oneself well. What has not been clearly assessed is whether
      the self-positivity bias influences the processing of incoming information as it
      unfolds in real time. In this study, we used event-related potentials to address
      this question. Participants read two-sentence social vignettes that were either
      self- or other-relevant. Pleasant words in self-relevant contexts evoked a
      smaller negativity between 300 and 500 ms (the N400 time window) than the same
      words in other-relevant contexts, suggesting that comprehenders were more likely
      to expect positive information when a scenario referred to themselves. This
      finding indicates that the self-positivity bias is available online, acting as a
      general schema that directly influences real-time comprehension. 

PMID- 25605968
TI  - Challenging emotional prejudice by changing self-concept: priming independent
      self-construal reduces racial in-group bias in neural responses to other's pain.
AB  - Humans show stronger empathy for in-group compared with out-group members'
      suffering and help in-group members more than out-group members. Moreover, the in
      group bias in empathy and parochial altruism tend to be more salient in
      collectivistic than individualistic cultures. This work tested the hypothesis
      that modifying self-construals, which differentiate between collectivistic and
      individualistic cultural orientations, affects in-group bias in empathy for
      perceived own-race vs other-race pain. By scanning adults using functional
      magnetic resonance imaging, we found stronger neural activities in the mid
      cingulate, left insula and supplementary motor area (SMA) in response to racial
      in-group compared with out-group members' pain after participants had been primed
      with interdependent self-construals. However, the racial in-group bias in neural
      responses to others' pain in the left SMA, mid-cingulate cortex and insula was
      significantly reduced by priming independent self-construals. Our findings
      suggest that shifting an individual's self-construal leads to changes of his/her
      racial in-group bias in neural responses to others' suffering. 

PMID- 25605969
TI  - Habitual condom use across partner type and sexual position among younger gay and
      bisexual men: findings from New Zealand HIV behavioural surveillance 2006-2011.
AB  - OBJECTIVES: Our objectives were to investigate demographic and behavioural
      factors associated with condom use and to examine how habitual condom use was
      across partner types and sexual positions among younger men who have sex with men
      (YMSM), aged 16-29, surveyed in New Zealand. METHODS: We analysed the 2006-2011
      national HIV behavioural surveillance data from YMSM who reported anal
      intercourse in four scenarios of partner type and sexual position: casual
      insertive, casual receptive, regular insertive and regular receptive. For each,
      respondents' condom use was classified as frequent (always/almost always) or
      otherwise, with associated factors identified with multivariate mixed-effect
      logistic regression. Habitual condom use across scenarios was examined using a
      latent variable technique that estimated the intraclass correlation coefficient
      (ICC). RESULTS: Frequent condom use was reported for 63.6% of 5153 scenarios
      reported from 2412 YMSM. Frequent use increased from boyfriend to fuckbuddy to
      casual partners. Infrequent use was associated with online recruitment, Pacific
      ethnicity, less education, HIV positivity, sex with women, having >=20 sexual
      partners versus 1 and reporting insertive and receptive sexual positions.
      Frequent condom use was associated with having two to five sexual partners versus
      one and shorter regular partnerships. The ICC=0.865 indicated highly habitual
      patterns of use; habitual infrequent condom use was most prevalent with regular
      partners (53.3%) and habitual frequent condom use was most prevalent with casual
      partners (70.2%) and for either sexual position (50.5% and 49.1%). CONCLUSIONS:
      Habitual condom use among YMSM highlights the value of early, engaging and
      sustained condom promotion. Public health should provide better and more
      compelling condom education, training and promotion for YMSM.

PMID- 25605971
TI  - A ligand for ALK.
AB  - The receptor tyrosine kinase ALK (anaplastic lymphoma kinase), as its name
      suggests, is aberrantly activated, mutated, or abundant in multiple cancers.
      Although widely studied in the context of cancer, the ligand that normally binds
      to and activates ALK in vertebrates has remained elusive. In this issue of
      Science Signaling, Murray and colleagues identify heparin as an ALK ligand. 

PMID- 25605970
TI  - Population and dyadic-based seroincidence of herpes simplex virus-2 and syphilis
      in southern India.
AB  - OBJECTIVES: Herpes simplex virus-2 (HSV-2) and syphilis are associated with
      increased risk of HIV, highlighting the importance of understanding their
      transmission dynamics. In India, most studies of HSV-2 and syphilis incidence are
      in high-risk populations and may not accurately reflect infectious activity. In
      this study, we aim to define HSV-2/syphilis incidence and risk factors in a
      population sample. METHODS: We conducted a longitudinal population-based survey
      in Andhra Pradesh, India, in two rounds: 2004-2005 and 2010-2011.
      Sociodemographic and behavioural data were collected, and dried blood spots
      tested for HSV-2 and Treponema pallidum IgG. After calculating sexually
      transmitted infection (STI) incidence, associated factors were assessed using
      modified Poisson regression and within-couple transmission rates modelled using
      seroconcordance/discordance data. RESULTS: 12,617 adults participated at baseline
      with 8494 at follow-up. Incidence of HSV-2 and syphilis per 1000 person-years was
      25.6 (95% CI 24.1 to 27.2) and 3.00 (95% CI 2.52 to 3.54). Incidence of HSV-2 was
      higher in women vs. men (31.1 vs. 20.2) and in rural vs urban residents (31.1 vs
      19.0) (p<0.05 for both). STI seroincidence increased in a step-wise fashion with
      age and was associated with spousal seropositivity for both sexes (incidence rate
      ratio (IRR) 2.59 to 6.78). Within couples the rate of transmission per 1000
      couple-years from men to women vs. women to men was higher for HSV-2 (193.3 vs.
      119.0) compared with syphilis (27.6 vs. 198.8), p<0.05 for both. CONCLUSIONS: HSV
      2 has higher incidence among subpopulations such as women, rural residents and
      older-aged individuals, suggesting a need for more generalised STI prevention
      approaches among populations traditionally considered low risk.

PMID- 25605972
TI  - Heparin is an activating ligand of the orphan receptor tyrosine kinase ALK.
AB  - Anaplastic lymphoma kinase (ALK) is one of the few remaining "orphan" receptor
      tyrosine kinases (RTKs) in which the ligands are unknown. Ligand-mediated
      activation of RTKs is important throughout development. ALK is particularly
      relevant to the development of the nervous system. Increased activation of RTKs
      by mutation, genetic amplification, or signals from the stroma contributes to
      disease progression and acquired drug resistance in cancer. Aberrant activation
      of ALK occurs in subsets of lung adenocarcinoma, neuroblastoma, and other
      cancers. We found that heparin is a ligand that binds specifically to the ALK
      extracellular domain. Whereas heparins with short chain lengths bound to ALK in a
      monovalent manner and did not activate the receptor, longer heparin chains
      induced ALK dimerization and activation in cultured neuroblastoma cells. Heparin
      lacking N- and O-linked sulfate groups or other glycosaminoglycans with sulfation
      patterns different than heparin failed to activate ALK. Moreover, antibodies that
      bound to the extracellular domain of ALK interfered with heparin binding and
      prevented heparin-mediated activation of ALK. Thus, heparin and perhaps related
      glycosaminoglycans function as ligands for ALK, revealing a potential mechanism
      for the regulation of ALK activity in vivo and suggesting an approach for
      developing ALK-targeted therapies for cancer. 

PMID- 25605974
TI  - The regulatory subunits of PI3Kgamma control distinct neutrophil responses.
AB  - Neutrophils, which migrate toward inflamed sites and kill pathogens by producing
      reactive oxygen species (ROS), are important in the defense against bacterial and
      fungal pathogens, but their inappropriate regulation causes various chronic
      inflammatory diseases. Phosphoinositide 3-kinase gamma (PI3Kgamma) functions
      downstream of proinflammatory G protein (heterotrimeric guanine nucleotide
      binding protein)-coupled receptors (GPCRs) in neutrophils and is a therapeutic
      target. In neutrophils, PI3Kgamma consists of a p110gamma catalytic subunit,
      which is activated by the guanosine triphosphatase Ras, and either a p84 or p101
      regulatory subunit. Loss or inhibition of p110gamma or expression of a Ras
      insensitive variant p110gamma (p110gamma(DASAA/DASAA)) impairs PIP3 production,
      Akt phosphorylation, migration, and ROS formation in response to GPCR activation.
      The p101 subunit binds to, and mediates PI3Kgamma activation by, G protein
      betagamma subunits, and p101(-/-) neutrophils have a similar phenotype to that of
      p110gamma(-/-) neutrophils, except that ROS responses are normal. We found that
      p84(-/-) neutrophils displayed reduced GPCR-stimulated PIP3 and Akt signaling,
      which was indistinguishable from that of p101(-/-) neutrophils. However, p84(-/-)
      neutrophils produced less ROS and exhibited normal migration in response to GPCR
      stimulation. These data suggest that p84-containing PI3Kgamma controls GPCR
      dependent ROS production. Thus, the PI3Kgamma regulatory subunits enable
      PI3Kgamma to mediate distinct neutrophil responses, which may occur by targeting
      PIP3 signaling into spatially distinct domains. 

PMID- 25605973
TI  - Synaptojanin 2 is a druggable mediator of metastasis and the gene is
      overexpressed and amplified in breast cancer.
AB  - Amplified HER2, which encodes a member of the epidermal growth factor receptor
      (EGFR) family, is a target of effective therapies against breast cancer. In
      search for similarly targetable genomic aberrations, we identified copy number
      gains in SYNJ2, which encodes the 5'-inositol lipid phosphatase synaptojanin 2,
      as well as overexpression in a small fraction of human breast tumors. Copy gain
      and overexpression correlated with shorter patient survival and a low abundance
      of the tumor suppressor microRNA miR-31. SYNJ2 promoted cell migration and
      invasion in culture and lung metastasis of breast tumor xenografts in mice.
      Knocking down SYNJ2 impaired the endocytic recycling of EGFR and the formation of
      cellular lamellipodia and invadopodia. Screening compound libraries identified
      SYNJ2-specific inhibitors that prevented cell migration but did not affect the
      related neural protein SYNJ1, suggesting that SYNJ2 is a potentially druggable
      target to block cancer cell migration. 

PMID- 25605975
TI  - Biological variation: a still evolving facet of laboratory medicine.

PMID- 25605976
TI  - Economic Status, Informal Exchange, and Sexual Risk in Kisumu, Kenya.
AB  - Many observers believe that wealthy men play a disproportionate role in the
      continuing spread of HIV/AIDS infection in sub-Saharan Africa through their
      involvement in informal exchange relationships, where money and gifts (referred
      to as "transfers") are given to a range of nonmarital sexual partners. In this
      case, wealthier men are riskier sexual partners because they can afford to give
      larger transfers, which have been found to be negatively associated with condom
      use. Alternatively, wealthier men might have greater incentives to practice safe
      sex at later stages of the epidemic or wealthier men might match with female
      partners who have particularly strong preferences for condom use. Accordingly,
      economic status would be positively associated with condom use. We use survey
      data from urban Kisumu, Kenya, to investigate the various mechanisms through
      which economic status is associated with sexual risk behavior. Our results show
      that wealth is positively associated with transfers; wealth is uncorrelated with
      condom use, however. The characteristics of wealthier men's female partners also
      do not differ from the characteristics of poorer men's partners. We conclude that
      wealthier men have stronger preferences for condom use, which offsets the
      negative effect of larger transfers that they give to their sexual partners.

PMID- 25605977
TI  - Trends in the Transitory Variance of Male Earnings: Methods and Evidence.
AB  - We estimate the trend in the transitory variance of male earnings in the U.S.
      using the Michigan Panel Study of Income Dynamics from 1970 to 2004. Using an
      error components model and simpler but only approximate methods, we find that the
      transitory variance started to increase in the early 1970s, continued to increase
      through the mid-1980s, and then remained at this new higher level through the
      1990s and beyond. Thus the increase mostly occurred about thirty years ago. Its
      increase accounts for between 31 and 49 percent of the total rise in cross
      sectional variance, depending on the time period.

PMID- 25605978
TI  - The Gender Gap in High School Physics: Considering the Context of Local
      Communities.
AB  - OBJECTIVES: We focus on variation in gender inequality in physics course-taking,
      questioning the notion of a ubiquitous male advantage. We consider how inequality
      in high school physics is related to the context of students' local communities,
      specifically the representation of women in STEM occupations in the labor force.
      METHODS: This study uses nationally representative data from the National
      Longitudinal Study of Adolescent Health (Add Health) and its education component,
      the Adolescent Health and Academic Achievement Transcript Study (AHAA). RESULTS:
      Approximately half of schools are characterized by either gender equality or even
      a small female advantage in enrollment in this traditionally male subject.
      Furthermore, variation in the gender gap in physics is related to the percent of
      women who are employed in STEM occupations within the community. CONCLUSION: Our
      study suggests that communities differ in the extent to which traditionally
      gendered status expectations shape beliefs and behaviors.

PMID- 25605979
TI  - Do the adult criminal careers of African Americans fit the "facts"?
AB  - PURPOSE: A major gap in the criminal career research is our understanding of
      offending among African Americans, especially beyond early adulthood. In light of
      this gap, this study describes the criminal career patterns of a cohort of
      African American males and females. METHODS: This paper uses official criminal
      history data spanning ages 17 to 52 from the Woodlawn Study, a community cohort
      of 1,242 urban African American males and females. We use basic descriptive
      statistics as well as group-based modeling to provide a detailed description of
      the various dimensions of their adult criminal careers. RESULTS: We find
      cumulative prevalence rates similar to those for African Americans from national
      probability sample estimates, yet participation in offending extends farther into
      midlife than expected with a substantial proportion of the cohort still engaged
      in offending into their 30s. CONCLUSIONS: The descriptive analyses contribute to
      the larger body of knowledge regarding the relationship between age and crime and
      the unfolding of the criminal career for African American males and females. The
      applicability of existing life course and developmental theories is discussed in
      light of the findings.

PMID- 25605980
TI  - A frailty model for interaction between multiple events.
AB  - Most models for categorical data rely on linear models in which higher order
      interactions are limited, usually to second order terms. Here we explore a
      dataset where second order interactions lead unavoidably to high order
      interactions. However in certain cases these interactions have a simple form
      which can be explained by population heterogeneity or 'frailty' and the Rasch
      model which uses a logistic structure is one such model. However its parameters
      are difficult to interpret. When event probabilities are low, we develop a simple
      model based on a multiplicative structure and a one-parameter gamma frailty model
      is developed to accommodate this sort of data. Moment estimators estimates are
      also provided for more general cases and goodness of fit statistics are given. An
      example involving 35 different human papillomavirus types in 33 614 women with
      normal cervical cytology smears (stratified by age) is explored.

PMID- 25605981
TI  - Genre-Specific Cultivation Effects: Lagged Associations between Overall TV
      Viewing, Local TV News Viewing, and Fatalistic Beliefs about Cancer Prevention.
AB  - Cultivation theory and research has been criticized for its failure to consider
      variation in effects by genre, employ appropriate third-variable controls, and
      determine causal direction. Recent studies, controlling for a variety of
      demographic characteristics and media use variables, have found that exposure to
      local television (TV) newscasts is associated with a variety of problematic "real
      world" beliefs. However, many of these studies have not adequately assessed
      causal direction. Redressing this limitation, we analyzed data from a two-wave
      national representative survey which permitted tests of lagged association
      between overall TV viewing, local TV news viewing, and fatalistic beliefs about
      cancer prevention. We first replicated the original cultivation effect and found
      a positive association between overall TV viewing at time 1 and increased
      fatalistic beliefs about cancer prevention at time 2. Analyses also provided
      evidence that local TV news viewing at time 1 predicts increased fatalistic
      beliefs about cancer prevention at time 2. There was little evidence for reverse
      causation in predicting changes in overall TV viewing or local TV news viewing.
      The paper concludes with a discussion of theoretical and practical implications
      of these findings.

PMID- 25605982
TI  - Age-independent effects of pubertal status on behavioral constraint in healthy
      adolescents.
AB  - Studies have examined age-related changes in personality traits from adolescence
      through young adulthood, finding that aspects of negative emotionality decrease
      while conscientiousness increases over time. Varied mechanisms may underlie these
      transitions, including puberty-driven hormonal changes. Here, healthy adolescents
      completed the Multidimensional Personality Questionnaire-Brief Form and self
      report measures of pubertal status at baseline and after two years. Independent
      of age, pubertal status impacted primary trait scales of the MPQ-BF Constraint
      factor in a sex-specific manner. Females decreased in Constraint, and
      particularly Control, while males increased in Constraint, and particularly Harm
      Avoidance, with advancing puberty. Longitudinal analyses validated these findings
      for Control. Findings are discussed relative to males' versus females'
      achievement of optimal levels of behavioral control in adolescence.

PMID- 25605983
TI  - Mass Spectrometric Analysis of Whole Secretome and Amylase-precipitated Secretome
      Proteins from Streptococcus gordonii.
AB  - Oral biofilm (dental plaque) is formed by the initial adhesion of "pioneer
      species" to salivary proteins that form the dental pellicle on the tooth surface.
      One such pioneer species, Streptococcus gordonii, is known to bind salivary
      amylase through specific amylase-binding proteins such as amylase-binding protein
      A (AbpA). Recent studies have demonstrated that once bound, salivary amylase
      appears to modulate gene expression in S. gordonii. However, it is not known if
      this amylase-induced gene expression leads to secretion of proteins that play a
      role in plaque biofilm formation. In this study we examined the differences in
      secreted proteomes between S. gordonii KS1 (wild type) and AbpA-deficient
      (DeltaAbpA) strains. We also examined the differentially precipitated secretome
      proteins following incubation with salivary amylase. The culture supernatants
      from KS1 and DeltaAbpA were analyzed by nano-LC/MS/MS to characterize the whole
      secreted proteomes of the KS1 and DeltaAbpA. A total of 107 proteins were
      identified in the KS1 and DeltaAbpA secretomes of which 72 proteins were
      predicted to have an N-terminal signal peptide for secretion. Five proteins were
      differentially expressed between the KS1 and DeltaAbpA secretomes; AbpA and
      sortase B were expressed exclusively by KS1, whereas Gdh, AdcA and GroEL were
      expressed only by DeltaAbpA. Incubation of culture supernatants from KS1 and
      DeltaAbpA with amylase (50 MUg/ml) at room temperature for 2 h resulted in the
      differential precipitation of secretome proteins. Hypothetical protein
      (SGO_0483), cation-transporting ATPase YfgQ (Aha1), isocitrate dehydrogenase
      (Icd), sortase A (SrtA), beta-N-acetylhexosaminidase (SGO_0405), peptide chain
      release factor 1(PrfA) and cardiolipin synthase (SGO_2037) were precipitated by
      amylase from the KS1 culture supernatant. Among the identified secreted proteins
      and amylase-precipitated proteins, transcriptional regulator LytR (SGO_0535) and
      cation-transporting ATPase YfgQ (Aha1) are potential signaling proteins.

PMID- 25605985
TI  - Copy number variations are progressively associated with the pathogenesis of
      colorectal cancer in ulcerative colitis.
AB  - AIM: To evaluate the association of known copy number variations (CNVs) in
      ulcerative colitis (UC) progressing to colorectal cancer. METHODS: Microsatellite
      instability analysis using the National Cancer Institute's panel of markers, and
      CNV association studies using Agilent 2 * 105 k arrays were done in tissue
      samples from four patient groups with UC: those at low risk (LR) or high risk of
      developing colorectal cancer, those with premalignant dysplastic lesions, and
      those with colitis-associated colorectal cancer (CAC). DNA from tissue samples of
      these groups were independently hybridized on arrays and analyzed. The data
      obtained were further subjected to downstream bioinformatics enrichment analysis
      to examine the correlation with CAC progression. RESULTS: Microarray analysis
      highlighted a progressive increase in the total number of CNVs [LR (n = 178) vs
      CAC (n = 958), 5.3-fold], gains and losses [LR (n = 37 and 141) vs CAC (n = 495
      and 463), 13.4- and 3.3-fold, respectively], size [LR (964.2 kb) vs CAC (10540
      kb), 10.9-fold] and the number of genes in such regions [LR (n = 119) vs CAC (n =
      455), 3.8-fold]. Chromosome-wise analysis of CNVs also showed an increase in the
      number of CNVs across each chromosome. There were 38 genes common to all four
      groups in the study; 13 of these were common to cancer genes from the Genetic
      Disease Association dataset. The gene set enrichment analysis and ontology
      analysis highlighted many cancer-associated genes. All the samples in the
      different groups were microsatellite stable. CONCLUSION: Increasing numbers of
      CNVs are associated with the progression of UC to CAC, and warrant further
      detailed exploration.

PMID- 25605984
TI  - Intraoperative endoscopic retrograde cholangio-pancreatography: a useful tool in
      the hands of the hepatobiliary surgeon.
AB  - AIM: To evaluate the efficacy of intraoperative endoscopic retrograde cholangio
      pancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) for
      patients with gall bladder stones (GS) and common bile duct stones (CBDS).
      METHODS: Patients treated for GS with CBDS were included. LC and intraoperative
      transcystic cholangiogram (TCC) were performed in most of the cases.
      Intraoperative ERCP was done for cases with proven CBDS. RESULTS: Eighty patients
      who had GS with CBDS were included. LC was successful in all cases.
      Intraoperative TCC revealed passed CBD stones in 4 cases so intraoperative ERCP
      was performed only in 76 patients. Intraoperative ERCP showed dilated CBD with
      stones in 64 cases (84.2%) where removal of stones were successful; passed stones
      in 6 cases (7.9%); short lower end stricture with small stones present in two
      cases (2.6%) which were treated by removal of stones with stent insertion; long
      stricture lower 1/3 CBD in one case (1.3%) which was treated by open
      hepaticojejunostomy; and one case (1.3%) was proved to be ampullary carcinoma and
      whipple's operation was scheduled. CONCLUSION: The hepatobiliary surgeon should
      be trained on ERCP as the third hand to expand his field of therapeutic options.

PMID- 25605986
TI  - Use of disposable graduated biopsy forceps improves accuracy of polyp size
      measurements during endoscopy.
AB  - AIM: To determine the accuracy of endoscopic polyp size measurements using
      disposable graduated biopsy forceps (DGBF). METHODS: Gradations accurate to 1 mm
      were assessed with the wire of disposable graduated biopsy forceps. When a polyp
      was noted, endoscopists determined the width of the polyp; then, the graduated
      biopsy forceps was inserted and the largest diameter of the tumor was measured.
      After excision, during surgery or endoscopy, the polyp was measured using the
      vernier caliper. RESULTS: One hundred and thirty-three colorectal polyps from 119
      patients were studied. The mean diameter, by post-polypectomy measurement, was
      0.92 +/- 0.69 cm; 83 were < 1 cm, 36 were between 1 and 2 cm, and 14 were > 2 cm.
      The mean diameter, by visual estimation, was 1.15 +/- 0.88 cm; compared to the
      actual size measured using vernier calipers, the difference was statistically
      significant. The mean diameter measured using the DGBF was 0.93 +/- 0.68 cm;
      compared to the actual size measured using vernier calipers, this difference was
      not statistically significant. The ratio between the mean size estimated by
      visual estimation and the actual size was significantly different from that
      between the mean size estimated using the DGBF and the actual size (1.26 +/- 0.30
      vs 1.02 +/- 0.11). CONCLUSION: The accuracy of polyp size estimation was low by
      visual assessment; however, it improved when the DGBF was used.

PMID- 25605987
TI  - Prevalence of Helicobacter pylori infection and atrophic gastritis in patients
      with dyspeptic symptoms in Myanmar.
AB  - AIM: To survey the detailed analyses for Helicobacter pylori (H. pylori)
      infection and gastric mucosal status in Myanmar. METHODS: A total of 252
      volunteers with dyspeptic symptoms (155 female and 97 male; mean age of 43.6 +/-
      14.2 years) was participated in Yangon and Mandalay. The status of H. pylori
      infection was determined based on 5 different tests including rapid urease test,
      culture, histology, immunohistochemistry and serology. Histological scores were
      evaluated according to the update Sydney system and the Operative Link for
      Gastritis Assessment system. Pepsinogen (PG) I and PG II were measured using
      enzyme-linked immunosorbent assays. RESULTS: The overall prevalence of H. pylori
      infection was 48.0%. There was no relationship between age and infection rate.
      Even in young group (less than 29 years old), the H. pylori infection rate was
      relatively high (41.9%). The prevalence of H. pylori infection was significantly
      higher in Yangon than that of Mandalay. H. pylori infection was significantly
      associated with the presence of gastric mucosal atrophy. All 7 subjects with
      peptic ulcer were infected with H. pylori. Although H. pylori-positive subjects
      showed stronger gastritis than H. pylori-negative subjects, most cases had mild
      gastritis. CONCLUSION: We revealed the prevalence of H. pylori infection in
      patients with dyspeptic symptoms in Myanmar. The H. pylori infection was a risk
      factor for peptic ulcer and stronger gastritis.

PMID- 25605988
TI  - Performance of American Society for Gastrointestinal Endoscopy guidelines for
      dyspepsia in Saudi population: prospective observational study.
AB  - AIM: To evaluate adherence of primary care physicians (PCPs) to international
      guidelines when referring patients for upper-gastrointestinal endoscopy (UGE),
      evaluate the importance of alarm symptoms and the performance of the American
      Society for Gastrointestinal Endoscopy (ASGE) guidelines in a Saudi population.
      METHODS: A prospective, observational cross-sectional study on dyspeptic patients
      undergoing UGE who were referred by PCPs over a 4 mo period. Referrals were
      classified as appropriate or inappropriate according to adherence to ASGE
      guidelines. RESULTS: Total of 221 dyspeptic patients was enrolled; 161 patients
      met our inclusion criteria. Mean age was 40.3 years (SD +/- 18.1). Females
      comprised 70.1%. Alarm symptoms included low hemoglobin level (39%), weight loss
      (18%), vomiting (16%), loss of appetite (16%), difficulty swallowing (3%), and
      gastrointestinal bleeding (3%). Abnormal endoscopy findings included gastritis
      (52%), duodenitis (10%), hiatus hernia (7.8%), features suggestive of celiac
      disease (6.5%), ulcers (3.9%), malignancy (2.6%) and gastroesophageal reflux
      disease (GERD: 17%). Among patients who underwent UGE, 63% met ASGE guidelines,
      and 50% had abnormal endoscopic findings. Endoscopy was not indicated in
      remaining 37% of patients. Among the latter group, endoscopy was normal in 54% of
      patients. There was no difference in proportion of abnormal endoscopic findings
      between two groups (P = 0.639). CONCLUSION: Dyspeptic patients had a low
      prevalence of important endoscopic lesions, and none of the alarm symptoms could
      significantly predict abnormal endoscopic findings.

PMID- 25605989
TI  - Response-guided treatment of cirrhotic chronic hepatitis B patients: multicenter
      prospective study.
AB  - AIM: To observe the effect of response-guided add-on therapy with adefovir (ADV)
      and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients. METHODS: A total of
      100 patients with CHB and cirrhosis were divided into three arms according to
      hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete
      response, HBV DNA <= 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000
      IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV
      was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological
      response, YMDD mutations, biochemical response, and liver function were
      evaluated. RESULTS: Comparison of the three arms demonstrated that early complete
      virologic response at week 24 was associated with maintained viral suppression
      (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%,
      respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144
      was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For
      patients who failed to achieve complete virological response at week 24,
      switching to combination therapy further decreased HBV DNA level by 1 log10
      IU/mL. All three arms obtained biochemical benefits including decline of alanine
      aminotransferase and elevation of albumin. In patients who developed HBV DNA
      breakthrough for YMDD mutations, ADV add-on therapy did not induce further
      multiple drug resistance to LAM or ADV. CONCLUSION: Optimized response-guided add
      on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves
      liver function in CHB patients with compensated liver cirrhosis.

PMID- 25605990
TI  - Berberine Prevents Intestinal Mucosal Barrier Damage During Early Phase of Sepsis
      in Rat through the Toll-Like Receptors Signaling Pathway.
AB  - Our previous study has shown berberine prevents damage to the intestinal mucosal
      barrier during early phase of sepsis in rat through mechanisms independent of the
      NOD-like receptors signaling pathway. In this study, we explored the regulatory
      effects of berberine on Toll-like receptors during the intestinal mucosal
      damaging process in rats. Male Sprague-Dawlay (SD) rats were treated with
      berberine for 5 d before undergoing cecal ligation and puncture (CLP) to induce
      polymicrobial sepsis. The expression of Toll-like receptor 2 (TLR 2), TLR 4, TLR
      9, the activity of nuclear factor-kappa B (NF-kappaB), the levels of selected
      cytokines and chemokines, percentage of cell death in intestinal epithelial
      cells, and mucosal permeability were investigated at 0, 2, 6, 12 and 24 h after
      CLP. Results showed that the tumor necrosis factor-alpha (TNF-alpha ) and
      interleukin-6 (IL-6) level were significantly lower in berberine-treated rats
      compared to the control animals. Conversely, the expression level of tight
      junction proteins, percentage of cell death in intestinal epithelial cells and
      the mucosal permeability were significantly higher in berberine-treated rats. The
      mRNA expression of TLR 2, TLR 4, and TLR 9 were significantly affected by
      berberine treatment. Our results indicate that pretreatment with berberine
      attenuates tissue injury and protects the intestinal mucosal barrier in early
      phase of sepsis and this may possibly have been mediated through the TLRs
      pathway. 

PMID- 25605991
TI  - Seasonal Acclimatization in Summer versus Winter to Changes in the Sweating
      Response during Passive Heating in Korean Young Adult Men.
AB  - We investigated the sweating response during passive heating (partial submersion
      up to the umbilical line in 42+/-0.5C water, 30 min) after summer and winter
      seasonal acclimatization (SA). Testing was performed in July during the summer,
      2011 [summer-SA; temp, 25.6+/-1.8C; relative humidity (RH), 82.1+/-8.2%] and in
      January during the winter, 2012 (winter-SA; temp, -2.7+/-2.9C; RH, 65.0+/-13.1%)
      in Cheonan (126 degrees 52'N, 33.38'E), Republic of Korea. All experiments were
      carried out in an automated climatic chamber (temp, 25.0+/-0.5C: RH, 60.0+/
      3.0%). Fifteen healthy men (age, 23.4+/-2.5 years; height, 175.0+/-5.9 cm;
      weight, 65.3+/-6.1 kg) participated in the study. Local sweat onset time was
      delayed during winter-SA compared to that after summer-SA (p< 0.001). Local sweat
      volume, whole body sweat volume, and evaporative loss volume decreased
      significantly after winter-SA compared to those after summer-SA (p<0.001).
      Changes in basal metabolic rate increased significantly after winter-SA (p<
      0.001), and tympanic temperature and mean body temperature were significantly
      lower after summer-SA (p<0.05). In conclusion, central sudomotor acitivity
      becomes sensitive to summer-SA and blunt to winter-SA in Rebubic of Korea. These
      results suggest that the body adjusts its temperature by economically controlling
      the sweating rate but does not lower the thermal dissipation rate through a more
      effective evaporation scheme after summer-SA than that after winter-SA. 

PMID- 25605992
TI  - Extremely low frequency magnetic field modulates the level of neurotransmitters.
AB  - This study was aimed to observe that extremely low frequency magnetic field (ELF
      MF) may be relevant to changes of major neurotransmitters in rat brain. After the
      exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of
      biogenic amines and their metabolites, amino acid neurotransmitters and nitric
      oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The
      exposure of ELF-MF for 2 or 5 days produced significant differences in
      norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum
      and hippocampus. Significant increases in the levels of serotonin and 5
      hydroxyindoleacetic acid were also observed in the striatum, thalamus or
      hippocampus. ELF-MF significantly increased the concentration of dopamine in the
      thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters
      such as glutamine, glycine and gamma -aminobutyric acid in the striatum and
      thalamus, whereas it decreased the levels in the cortex, cerebellum and
      hippocampus. ELF-MF significantly increased NO concentration in the striatum,
      thalamus and hippocampus. The present study has demonstrated that exposure to ELF
      MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in
      the brain although the extent and property vary with the brain areas. However,
      the mechanisms remain further to be characterized. 

PMID- 25605993
TI  - Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts
      from Artemisia annua L.
AB  - The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin
      derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L.
      were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory
      effects. Of these, the acetone extract had the greatest inhibitory effect on
      lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2), and
      proinflammatory cytokine (IL-1beta , IL-6, and IL-10) production. Antioxidant
      activity evaluations revealed that the ethanol extract had the highest free
      radical scavenging activity, (91.0+/-3.2%), similar to alpha-tocopherol (99.9%).
      The extracts had antimicrobial activity against the periodontopathic
      microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum
      subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella
      intermedia. This study shows that Artemisia annua L. extracts contain anti
      inflammatory, antioxidant, and antimicrobial substances and should be considered
      for use in pharmaceutical products for the treatment of dental diseases. 

PMID- 25605994
TI  - ERK Activation by Fucoidan Leads to Inhibition of Melanogenesis in Mel-Ab Cells.
AB  - Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the
      class Phaeophyceae, has been widely studied for its possible health benefits.
      However, the potential of fucoidan as a possible treatment for hyperpigmentation
      is not fully understood. This study investigated the effects of fucoidan on
      melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan
      significantly decreased melanin content. While fucoidan treatment decreased
      tyrosinase activity, it did not do so directly. Western blot analysis indicated
      that fucoidan downregulated microphthalmia-associated transcription factor and
      reduced tyrosinase protein expression. Further investigation showed that fucoidan
      activated the extracellular signal-regulated kinase (ERK) pathway, suggesting a
      possible mechanism for the inhibition of melanin synthesis. Treatment with
      PD98059, a specific ERK inhibitor, resulted in the recovery of melanin
      production. Taken together, these findings suggest that fucoidan inhibits
      melanogenesis via ERK phosphorylation. 

PMID- 25605995
TI  - Isolation and in vitro culture of vascular endothelial cells from mice.
AB  - In cardiovascular disorders, understanding of endothelial cell (EC) function is
      essential to elucidate the disease mechanism. Although the mouse model has many
      advantages for in vivo and in vitro research, efficient procedures for the
      isolation and propagation of primary mouse EC have been problematic. We describe
      a high yield process for isolation and in vitro culture of primary EC from mouse
      arteries (aorta, braches of superior mesenteric artery, and cerebral arteries
      from the circle of Willis). Mouse arteries were carefully dissected without
      damage under a light microscope, and small pieces of the vessels were transferred
      on/in a Matrigel matrix enriched with endothelial growth supplement. Primary
      cells that proliferated in Matrigel were propagated in advanced DMEM with fetal
      calf serum or platelet-derived serum, EC growth supplement, and heparin. To
      improve the purity of the cell culture, we applied shearing stress and anti
      fibroblast antibody. EC were characterized by a monolayer cobble stone
      appearance, positive staining with acetylated low density lipoprotein labeled
      with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate, RT-PCR
      using primers for von-Willebrand factor, and determination of the protein level
      endothelial nitric oxide synthase. Our simple, efficient method would facilitate
      in vitro functional investigations of EC from mouse vessels. 

PMID- 25605996
TI  - Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats.
AB  - It has been shown that the extracts including eupatilin and quercetin-3-beta-D
      glucuronopyranoside had mucoprotective effects on the esophagus and stomach
      through their antioxidant activities. This study was designed to investigate the
      anti-inflammatory effect of these flavonoid compounds in an animal model of
      inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid.
      Experimental colitis was induced by intracolonic administration of 2,4,6
      trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-beta-D
      glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to
      the induction of colitis and then again 24 h later. The animals were sacrificed
      48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic
      appearance of the colonic lesions was scored in a blinded manner on a scale of 1
      to 10. The inflammatory response to colitis induction was assessed by measuring
      myeloperoxidase activity, nitric oxide production, tumor necrosis factor-alpha
      expression, total glutathione levels, and malondialdehyde concentrations in the
      colon. The results indicated that extracts including eupatilin and extracts
      including quercetin-3-beta-D-glucuronopyranoside dose-dependently improved the
      morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and
      reduced the ulcer index accordingly. In addition, rats receiving extracts
      including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside
      showed significantly decreased levels of mucosal myeloperoxidase activity, nitric
      oxide production, tumor necrosis factor-alpha expression, and malondialdehyde
      levels, and increased total glutathione levels. Extracts including eupatilin and
      extracts including quercetin-3-beta-D-glucuronopyranoside ameliorated the
      inflammatory response and colonic injury in acute colitis by decreasing oxidative
      stress and neutrophil activation. Extracts including eupatilin and extracts
      including quercetin-3-beta-D-glucuronopyranoside may inhibit acute colitis. 

PMID- 25605997
TI  - Peptidoglycan Induces the Production of Interleukin-8 via Calcium Signaling in
      Human Gingival Epithelium.
AB  - The etiology of periodontal disease is multifactorial. Exogenous stimuli such as
      bacterial pathogens can interact with toll-like receptors to activate
      intracellular calcium signaling in gingival epithelium and other tissues. The
      triggering of calcium signaling induces the secretion of pro-inflammatory
      cytokines such as interleukin-8 as part of the inflammatory response; however,
      the exact mechanism of calcium signaling induced by bacterial toxins when
      gingival epithelial cells are exposed to pathogens is unclear. Here, we
      investigate calcium signaling induced by bacteria and expression of inflammatory
      cytokines in human gingival epithelial cells. We found that peptidoglycan, a
      constituent of gram-positive bacteria and an agonist of toll-like receptor 2,
      increases intracellular calcium in a concentration-dependent manner.
      Peptidoglycan-induced calcium signaling was abolished by treatment with blockers
      of phospholipase C (U73122), inositol 1,4,5-trisphosphate receptors, indicating
      the release of calcium from intracellular calcium stores. Peptidoglycan-mediated
      interleukin-8 expression was blocked by U73122 and 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). Moreover, interleukin
      8 expression was induced by thapsigargin, a selective inhibitor of the
      sarco/endoplasmic reticulum calcium ATPase, when thapsigargin was treated alone
      or co-treated with peptidoglycan. These results suggest that the gram-positive
      bacterial toxin peptidoglycan induces calcium signaling via the phospholipase
      C/inositol 1,4,5-trisphosphate pathway, and that increased interleukin-8
      expression is mediated by intracellular calcium levels in human gingival
      epithelial cells. 

PMID- 25605998
TI  - Pectin Micro- and Nano-capsules of Retinyl Palmitate as Cosmeceutical Carriers
      for Stabilized Skin Transport.
AB  - Retinyl palmitate (RP)-loaded pectinate micro- and nano-particles (PMP and PNP)
      were designed for stabilization of RP that is widely used as an anti-wrinkle
      agent in anti-aging cosmeceuticals. PMP/PNP were prepared with an ionotropic
      gelation method, and anti-oxidative activity of the particles was measured with a
      DPPH assay. The stability of RP in the particles along with pectin gel and
      ethanolic solution was then evaluated. In vitro release and skin permeation
      studies were performed using Franz diffusion cells. Distribution of RP in each
      skin tissue (stratum corneum, epidermis, and dermis) was also determined. PMP and
      PNP could be prepared with mean particle size diameters of 593~843 MUm (PMP) and
      530 nm (i.e., 0.53 MUm, PNP). Anti-oxidative activity of PNP was greater than PMP
      due largely to larger surface area available for PNP. The stability of RP in PMP
      and PNP was similar but much greater than RP in pectin bulk gels and ethanolic
      solution. PMP and PNP showed the abilities to constantly release RP and it could
      be permeated across the model artificial membrane and rat whole skin. RP was
      serially deposited throughout the skin layers. This study implies RP loaded PMP
      and PNP are expected to be advantageous for improved anti-wrinkle effects. 

PMID- 25605999
TI  - Airway Smooth Muscle Sensitivity to Methacholine in Precision-Cut Lung Slices
      (PCLS) from Ovalbumin-induced Asthmatic Mice.
AB  - Asthma is a chronic inflammatory disease characterized by airway
      hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh)
      is widely used in broncho-provocation test to evaluate airway resistance. For
      experimental investigation, ovalbumin-induced sensitization is frequently used in
      rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo,
      it remains unclear whether the MCh sensitivity of airway smooth muscle isolated
      from Ova-asthma is persistently changed. In this study, the contractions of
      airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13
      overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway
      lumen space (AW). The airway resistance in vivo was measured using
      plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed
      in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh
      concentration-dependent narrowing of airway lumen (DeltaAW) was observed. In
      contrast to the AHR in vivo, the EC50 of MCh for DeltaAW from Ova-asthma and IL
      13TG were not different from control, indicating unchanged sensitivity to MCh.
      Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma,
      the change was also statistically insignificant. Membrane depolarization-induced
      DeltaAW by 60 mM K(+) (60K-contraction) was larger in IL-13TG than control,
      whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin
      induced DeltaAW of Ova-asthma was smaller than control and IL-13TG. Taken
      together, the AHR in Ova-asthma and IL-13TG are not reflected in the
      contractility of isolated airways from PCLS. The AHR of the model animals seems
      to require intrinsic agonists or inflammatory microenvironment that is washable
      during tissue preparation. 

PMID- 25606000
TI  - Bisphenol A and 4-tert-Octylphenol Inhibit Cx46 Hemichannel Currents.
AB  - Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ)
      channels. Cx46 and Cx50 are also known to function as conductive hemichannels. As
      part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors
      were used to examine their effect on Cx46 hemichannels expressed in Xenopus
      oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by
      slowly activating outward currents and relatively fast inward tail currents.
      Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18%
      of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, 1 uM)
      reversibly reduced outward hemichannel currents up to ~28% (n=4). However,
      overall shapes of Cx46 hemichannel current traces (outward and inward currents)
      were not changed by these drugs. These results suggest that BPA and OP are likely
      to occupy the pore of Cx46 hemichannels and thus obstruct the ionic fluxes. This
      finding provides that BPA and OP are potential candidates for GJ channel
      blockers. 

PMID- 25606001
TI  - An easy, rapid, and cost-effective method for DNA extraction from various lichen
      taxa and specimens suitable for analysis of fungal and algal strains.
AB  - Lichen studies, including biodiversity, phylogenetic relationships, and
      conservation concerns require definitive species identification, however many
      lichens can be challenging to identify at the species level. Molecular techniques
      have shown efficacy in discriminating among lichen taxa, however, obtaining
      genomic DNA from herbarium and fresh lichen thalli by conventional methods has
      been difficult, because lichens contain high proteins, polysaccharides, and other
      complex compounds in their cell walls. Here we report a rapid, easy, and
      inexpensive protocol for extracting PCR-quality DNA from various lichen species.
      This method involves the following two steps: first, cell breakage using a
      beadbeater; and second, extraction, isolation, and precipitation of genomic DNA.
      The procedure requires approximately 10 mg of lichen thalli and can be completed
      within 20 min. The obtained DNAs were of sufficient quality and quantity to
      amplify the internal transcribed spacer region from the fungal and algal lichen
      components, as well as to sequence the amplified products. In addition, 26
      different lichen taxa were tested, resulting in successful PCR products. The
      results of this study validated the experimental protocols, and clearly
      demonstrated the efficacy and value of our KCl extraction method applied in the
      fungal and algal samples. 

PMID- 25606002
TI  - Entomopathogenicity of Simplicillium lanosoniveum Isolated in Korea.
AB  - Fruiting bodies similar to those of the ascomycete fungi Podostroma cornu-damae
      and Cordyceps militaris were collected from Mt. Seunghak in Busan, Korea on
      August 21, 2012. The fruiting bodies were cylindrical, with tapered ends and
      golden red in color. The fruiting bodies contained abundant conidiophores bearing
      single-celled conidia, but no perithecia or asci. Pure culture of the fungal
      isolates was obtained through single-spore isolation. Analyses of morphological
      characteristics, including conidia shape, and phylogenetic traits, using internal
      transcribed spacer sequences, showed that these isolates belonged to the species
      Simplicillium lanosoniveum. Although this fungal species is known to be
      mycoparasitic, the isolates obtained in this study were unable to infect fungi.
      However, silkworms (Bombyx mori) inoculated with the fungal isolates died during
      the larval or pupal stages, as has been shown for the strongly entomopathogenic
      fungus Beauveria bassiana. This study is the first report of the
      entomopathogenicity of S. lanosoniveum and indicates its potential for use in
      biological control of insects. 

PMID- 25606003
TI  - Genome-Wide Identification and Characterization of Novel Laccase Genes in the
      White-Rot Fungus Flammulina velutipes.
AB  - The aim of this study was to identify and characterize new Flammulina velutipes
      laccases from its whole-genome sequence. Of the 15 putative laccase genes
      detected in the F. velutipes genome, four new laccase genes (fvLac-1, fvLac-2,
      fvLac3, and fvLac-4) were found to contain four complete copper-binding regions
      (ten histidine residues and one cysteine residue) and four cysteine residues
      involved in forming disulfide bridges, fvLac-1, fvLac-2, fvLac3, and fvLac-4,
      encoding proteins consisting of 516, 518, 515, and 533 amino acid residues,
      respectively. Potential N-glycosylation sites (Asn-Xaa-Ser/Thr) were identified
      in the cDNA sequence of fvLac-1 (Asn-454), fvLac-2 (Asn-437 and Asn-455), fvLac-3
      (Asn-111 and Asn-237), and fvLac4 (Asn-402 and Asn-457). In addition, the first
      19~20 amino acid residues of these proteins were predicted to comprise signal
      peptides. Laccase activity assays and reverse transcription polymerase chain
      reaction analyses clearly reveal that CuSO4 affects the induction and the
      transcription level of these laccase genes. 

PMID- 25606004
TI  - Effects of Water Stress on the Endophytic Fungal Communities of Pinus koraiensis
      Needles Infected by Cenangium ferruginosum.
AB  - To examine the effects of water stress and Cenangium ferruginosum (CF) on the
      fungal endophytic community of needles of Pinus koraiensis (PK), fungal
      endophytes isolated from the needles of 5-year-old PK seedlings were compared
      before and after exposure to water stress conditions and artificial inoculation
      with CF ascospores. Artificial CF inoculation was successfully confirmed using
      PCR with CF-specific primers (CfF and CfR). For comparison of the degree of water
      deficit in water-stressed and control groups of PK seedlings infected with CF,
      the water saturation deficit and water potential were measured. Lower water
      potential estimates were found in the water-stressed seedlings than in the
      control group. The fungal endophytes isolated from the second-year needles of non
      water-stressed seedlings before and after CF inoculation revealed that primary
      saprobes were approximately 30% and 71.7%, respectively, and the remaining
      endophytes were rot fungi or pathogens. Sixty days after CF inoculation, diverse
      fungal endophytes in the first-year needles were isolated from the water-stressed
      seedlings. However, some fungal endophytes isolated from the non-water-stressed
      seedlings were also identified. Fungal endophytes in the second-year needles of
      the water-stressed and non-water-stressed seedlings were approximately 8% and
      71.7% of saprobes, respectively, and the remaining endophytes were rot fungi or
      pathogens. On the basis of the results, we conclude that water deficit and CF can
      have an effect on fungal endophytic communities in the needles of PK seedlings. 

PMID- 25606005
TI  - Incidence and level of aflatoxins contamination in medicinal plants in Korea.
AB  - During 2011~2013, a total of 729 samples for 19 types of medicinal plant were
      collected from Seoulyekryungsi in Seoul, Korea, and investigated for the presence
      of aflatoxins. The samples were analyzed using immunoaffinity column cleanup and
      high-performance liquid chromatography coupled to a fluorescence detector after
      post-column derivatization. Aflatoxins were found in 124 out of the 729 analyzed
      samples: 65 containing aflatoxin B1 (AFB1), 24 with aflatoxin B2 (AFB2), 15 with
      aflatoxin G1 (AFG1), and 20 samples with aflatoxin G2 (AFG2). The ranges for
      positive samples were 0.1~404.7 ug/kg for AFB1, 0.1~10.0 ug/kg for AFB2,
      0.1~635.3 ug/kg for AFG1, 0.1~182.5 ug/kg for AFG2, and 0.1~1,043.9 ug/kg for
      total aflatoxins. Most of the medicinal plant samples (721, 98.9%) were below
      legal limits, but 8 samples exceeded the legal limits of 10 and 15 ug/kg
      established by the Korean standard for AFB1 and total aflatoxins (the sum of
      AFB1, AFB2, AFG1 and AFG2), respectively. 

PMID- 25606006
TI  - Influence of Additives on the Yield and Pathogenicity of Conidia Produced by
      Solid State Cultivation of an Isaria javanica Isolate.
AB  - Recently, the Q biotype of tobacco whitefly has been recognized as the most
      hazardous strain of Bemisia tabaci worldwide, because of its increased resistance
      to some insecticide groups. As an alternative control agent, we selected an
      Isaria javanica isolate as a candidate for the development of a mycopesticide
      against the Q biotype of sweet potato whitefly. To select optimal mass production
      media for solid-state fermentation, we compared the production yield and
      virulence of conidia between 2 substrates (barley and brown rice), and we also
      compared the effects of various additives on conidia production and virulence.
      Barley was a better substrate for conidia production, producing 3.43 * 10(10)
      conidia/g, compared with 3.05 * 10(10) conidia/g for brown rice. The addition of
      2% CaCO3 + 2% CaSO4 to barley significantly increased conidia production.
      Addition of yeast extract, casein, or gluten also improved conidia production on
      barley. Gluten addition (3% and 1.32%) to brown rice improved conidia production
      by 14 and 6 times, respectively, relative to brown rice without additives.
      Conidia cultivated on barley produced a mortality rate of 62% in the sweet potato
      whitefly after 4-day treatment, compared with 53% for conidia cultivated on brown
      rice. The amendment of solid substrate cultivation with additives changed the
      virulence of the conidia produced; the median lethal time (LT50) was shorter for
      conidia produced on barley and brown rice with added yeast extract (1.32% and 3%,
      respectively), KNO3 (0.6% and 1%), or gluten (1.32% and 3%) compared with conidia
      produced on substrates without additives. 

PMID- 25606007
TI  - Metabolite Profiling during Fermentation of Makgeolli by the Wild Yeast Strain
      Saccharomyces cerevisiae Y98-5.
AB  - Makgeolli is a traditional Korean alcoholic beverage. The flavor of makgeolli is
      primarily determined by metabolic products such as free sugars, amino acids,
      organic acids, and aromatic compounds, which are produced during the fermentation
      of raw materials by molds and yeasts present in nuruk, a Korean fermentation
      starter. In this study, makgeolli was brewed using the wild yeast strain
      Saccharomyces cerevisiae Y98-5, and temporal changes in the metabolites during
      fermentation were analyzed by ultra-high-performance liquid chromatography
      quadrupole-time-of-flight mass spectrometry. The resultant data were analyzed by
      partial least squares-discriminant analysis (PLS-DA). Various metabolites,
      including amino acids, organic acids, sugar alcohols, small peptides, and
      nucleosides, were obviously altered by increasing the fermentation period.
      Changes in these metabolites allowed us to distinguish among makgeolli samples
      with different fermentation periods (1, 2, 3, 6, 7, and 8 days) on a PLS-DA score
      plot. In the makgeolli brewed in this study, the amounts of tyrosine (463.13
      ug/mL) and leucine (362.77 ug/mL) were high. Therefore, our results indicate that
      monitoring the changes in metabolites during makgeolli fermentation might be
      important for brewing makgeolli with good nutritional quality. 

PMID- 25606008
TI  - Identification of Wild Yeast Strains and Analysis of Their beta-Glucan and
      Glutathione Levels for Use in Makgeolli Brewing.
AB  - Makgeolli, also known as Takju, is a non-filtered traditional Korean alcoholic
      beverage that contains various floating matter, including yeast cells, which
      contributes to its high physiological functionality. In the present study, we
      assessed the levels of beta-glucan and glutathione in various yeast strains
      isolated from traditional Korean Nuruk and selected a beta-glucan- and
      glutathione-rich yeast strain to add value to Makgeolli by enhancing its
      physiological functionality through increased levels of these compounds. Yeast
      beta-glucan levels ranged from 6.26% to 32.69% (dry basis) and were strongly
      species-dependent. Dried Saccharomyces cerevisiae isolated from Nuruk contained
      25.53 ug/mg glutathione, 0.70 ug/mg oxidized glutathione, and 11.69 ug/g and
      47.85 ug/g spermidine and L-ornithine monohydrochloride, respectively. To produce
      functional Makgeolli, a beta-glucan- and glutathione-rich yeast strain was
      selected in a screening analysis. Makgeolli fermented with the selected yeast
      strain contained higher beta-glucan and glutathione levels than commercial
      Makgeolli. Using the selected yeast strain to produce Makgeolli with high beta
      glucan and glutathione content may enable the production of functional Makgeolli.

PMID- 25606009
TI  - Bioconversion of Ginsenosides from Red Ginseng Extract Using Candida allociferrii
      JNO301 Isolated from Meju.
AB  - Red ginseng (Panax ginseng), a Korean traditional medicinal plant, contains a
      variety of ginsenosides as major functional components. It is necessary to remove
      sugar moieties from the major ginsenosides, which have a lower absorption rate
      into the intestine, to obtain the aglycone form. To screen for microorganisms
      showing bioconversion activity for ginsenosides from red ginseng, 50 yeast
      strains were isolated from Korean traditional meju (a starter culture made with
      soybean and wheat flour for the fermentation of soybean paste). Twenty strains in
      which a black zone formed around the colony on esculin-yeast malt agar plates
      were screened first, and among them 5 strains having high beta-glucosidase
      activity on p-nitrophenyl-beta-D-glucopyranoside as a substrate were then
      selected. Strain JNO301 was finally chosen as a bioconverting strain in this
      study on the basis of its high bioconversion activity for red ginseng extract as
      determined by thin-layer chromatography (TLC) analysis. The selected
      bioconversion strain was identified as Candida allociferrii JNO301 based on the
      nucleotide sequence analysis of the 18S rRNA gene. The optimum temperature and pH
      for the cell growth were 20~30C and pH 5~8, respectively. TLC analysis confirmed
      that C. allociferrii JNO301 converted ginsenoside Rb1 into Rd and then into F2,
      Rb2 into compound O, Rc into compound Mc1, and Rf into Rh1. Quantitative analysis
      using high-performance liquid chromatography showed that bioconversion of red
      ginseng extract resulted in an increase of 2.73, 3.32, 33.87, 16, and 5.48 fold
      in the concentration of Rd, F2, compound O, compound Mc1, and Rh1, respectively. 

PMID- 25606010
TI  - Control of Root Rot and Wilt Diseases of Roselle under Field Conditions.
AB  - Roselle (Hibiscus sabdariffa L.) is one of the most important medicinal crops in
      many parts of the world. In this study, the effects of microelements,
      antioxidants, and bioagents on Fusarium oxysporum, F. solani, and Macrophomina
      phaseolina, the causal pathogens of root rot and wilt diseases in roselle, were
      examined under field conditions. Preliminary studies were carried out in vitro in
      order to select the most effective members to be used in field control trials.
      Our results showed that microelements (copper and manganese), antioxidants
      (salicylic acid, ascorbic acid, and EDTA), a fungicide (Dithane M45) and
      biological control agents (Trichoderma harzianum and Bacillus subtilis) were
      significantly reduced the linear growth of the causal pathogens. Additionally,
      application of the previous microelements, antioxidants, a fungicide and
      biological control agents significantly reduced disease incidence of root rot and
      wilt diseases under field conditions. Copper, salicylic acid, and T. harzianum
      showed the best results in this respect. In conclusion, microelements,
      antioxidants, and biocontrol agents could be used as alternative strategies to
      fungicides for controlling root rot and wilt diseases in roselle. 

PMID- 25606011
TI  - Virulence of Entomopathogenic Fungi Metarhizium anisopliae and Paecilomyces
      fumosoroseus for the Microbial Control of Spodoptera exigua.
AB  - The beet armyworm Spodoptera exigua (Lepidoptera: Noctuidae) is difficult to
      control using chemical insecticides because of the development of insecticide
      resistance. Several pest control agents are used to control the beet armyworm.
      Entomopathogenic fungi are one of the candidates for eco-friendly pest control
      instead of chemical control agents. In this study, among various entomopathogenic
      fungal strains isolated from soil two isolates were selected as high virulence
      pathogens against larva of beet armyworm. Control efficacy of fungal conidia was
      influenced by conidia concentration, temperature, and relative humidity (RH). The
      isolates Metarhizium anisopliae FT83 showed 100% cumulative mortality against
      second instar larvae of S. exigua 3 days after treatment at 1 * 10(7) conidia/mL
      and Paecilomyces fumosoroseus FG340 caused 100% mortality 6 days after treatment
      at 1 * 10(4) conidia/mL. Both M. anisopliae FT83 and P. fumosoroseus FG340
      effectively controlled the moth at 20~30C. M. anisopliae FT83 was significantly
      affected mortality by RH: mortality was 86.7% at 85% RH and 13.4% at 45% RH. P.
      fumosoroseus FG340 showed high mortality as 90% at 45% RH and 100% at 75% RH 6
      days after conidia treatments. These results suggest that P. fumosoroseus FG340
      and M. anisopliae FT83 have high potential to develop as a biocontrol agent
      against the beet armyworm. 

PMID- 25606012
TI  - First Report of the Ash Dieback Pathogen Hymenoscyphus fraxineus in Korea.
AB  - In the past two decades, European ash trees (Fraxinus spp.) have been severely
      damaged due to ash dieback disease, which is caused by the fungal species
      Hymenoscyphus fraxineus (Chalara fraxinea in the anamorphic stage). Recent
      molecular phylogenetic and population genetic studies have suggested that this
      fungus has been introduced from Asia to Europe. During a fungal survey in Korea,
      H. fraxineus-like apothecia were collected from fallen leaves, rachises, and
      petioles of Korean ash and Manchurian ash trees. The morphological and ecological
      traits of these materials are described with the internal transcribed spacer rDNA
      sequence comparison of H. fraxineus strains collected from Korea, China and
      Japan. 

PMID- 25606013
TI  - A New Record of Pseudallescheria boydii Isolated from Crop Field Soil in Korea.
AB  - Pseudallescheria boydii KNU13-2 was isolated from crop field soil and identified
      by analysis of internal transcribed spacer regions of rDNA and morphological
      characteristics. In the literature, P. boydii has been mentioned as a human
      pathogen. This is the first record of P. boydii isolated from crop field soil in
      Korea. 

PMID- 25606014
TI  - First Report of Mortierella alpina (Mortierellaceae, Zygomycota) Isolated from
      Crop Field Soil in Korea.
AB  - A new recorded species of Mortierella was recovered during the investigation of
      fungal communities in soil samples collected from different locations of Gangwon
      do, Korea. The species was identified and described as Mortierella alpina on the
      basis of phylogenetic analysis of internal transcribed spacer sequences and
      morphological characteristics. This species has not been officially reported from
      Korea thus far. 

PMID- 25606015
TI  - First Record of Alternaria simsimi Causing Leaf Spot on Sesame (Sesamum indicum
      L.) in Korea.
AB  - Leaf spot disease was observed in sesame (Sesamum indicum L.) during 2009 and
      2010 in Korea. The pathogen was identified as Alternaria simsimi based on
      morphological and cultural characteristics. The morphological identification was
      well supported by phylogenetic analysis of the ribosomal DNA-internal transcribed
      spacer region. A. simsimi isolates caused spot symptoms on leaves and stems of
      sesame plants 2 wk after artificial inoculation, which were similar to those
      observed in the field. This is the first record of leaf spot disease in Korea
      caused by A. simsimi. 

PMID- 25606016
TI  - The First Report of Postharvest Stem Rot of Kohlrabi Caused by Sclerotinia
      sclerotiorum in Korea.
AB  - In March 2014, a kohlrabi stem rot sample was collected from the cold storage
      room of Daegwallyong Horticultural Cooperative, Korea. White and fuzzy mycelial
      growth was observed on the stem, symptomatic of stem rot disease. The pathogen
      was isolated from the infected stem and cultured on potato dextrose agar for
      further fungal morphological observation and to confirm its pathogenicity,
      according to Koch's postulates. Morphological data, pathogenicity test results,
      and rDNA sequences of internal transcribed spacer regions (ITS 1 and 4) showed
      that the postharvest stem rot of kohlrabi was caused by Sclerotinia sclerotiorum.
      This is the first report of postharvest stem rot of kohlrabi in Korea. 

PMID- 25606017
TI  - Characterization and Pathogenicity of Alternaria vanuatuensis, a New Record from
      Allium Plants in Korea and China.
AB  - Alternaria from different Allium plants was characterized by multilocus sequence
      analysis. Based on sequences of the beta-tubulin (BT2b), the Alternaria allergen
      a1 (Alt a1), and the RNA polymerase II second largest subunit (RPB2) genes and
      phylogenetic data analysis, isolates were divided into two groups. The two groups
      were identical to representative isolates of A. porri (EGS48-147) and A.
      vanuatuensis (EGS45-018). The conidial characteristics and pathogenicity of A.
      vanuatuensis also well supported the molecular characteristics. This is the first
      record of A. vanuatuensis E. G. Simmons & C. F. Hill from Korea and China. 

PMID- 25606018
TI  - Root Age-Dependent Changes in Arbuscular Mycorrhizal Fungal Communities
      Colonizing Roots of Panax ginseng.
AB  - In this study, we examined arbuscular mycorrhizal fungal (AMF) community
      structure colonizing field-cultivated ginseng roots according of different ages,
      such as 1- to 5-year-old plant, collected from Geumsan-gun, Korea. A total of
      seven AMF species namely, Funnelliformis caledonium, F. moseae, Gigaspora
      margarita, Paraglomus laccatum, P. occultum, Rhizophagus irregularis, and
      Scutellospora heterogama were identified from the roots using cloning, PCR
      restriction fragment length polymorphism and sequence analysis of the large
      subunit region in rDNA. AMF species diversity in the ginseng roots decreased with
      the increase in root age because of the decreased species evenness. In addition,
      the community structures of AMF in the roots became more uniform. These results
      suggest that the age of ginseng affects mycorrhizal colonization and its
      community structure. 

PMID- 25606019
TI  - Role of LAMMER Kinase in Cell Wall Biogenesis during Vegetative Growth of
      Aspergillus nidulans.
AB  - Depending on the acquisition of developmental competence, the expression of genes
      for beta-1,3-glucan synthase and chitin synthase was affected in different ways
      by Aspergillus nidulans LAMMER kinase. LAMMER kinase deletion, DeltalkhA, led to
      decrease in beta-1,3-glucan, but increase in chitin content. The DeltalkhA strain
      was also resistant to nikkomycin Z. 

PMID- 25606020
TI  - Mitochondrial Protein Nfu1 Influences Homeostasis of Essential Metals in the
      Human Fungal Pathogen Cryptococcus neoformans.
AB  - Mitochondrial protein Nfu1 plays an important role in the assembly of
      mitochondrial Fe-S clusters and intracellular iron homeostasis in the model yeast
      Saccharomyces cerevisiae. In this study, we identified the Nfu1 ortholog in the
      human fungal pathogen Cryptococcus neoformans. Our data showed that C. neoformans
      Nfu1 localized in the mitochondria and influenced homeostasis of essential metals
      such as iron, copper and manganese. Marked growth defects were observed in the
      mutant lacking NFU1, which suggests a critical role of Nfu1 in Fe-S cluster
      biosynthesis and intracellular metal homeostasis in C. neoformans. 

PMID- 25606021
TI  - Developing a primary care research agenda through collaborative efforts - a
      proposed "6E" model.
AB  - BACKGROUND: Primary care research is at a crossroad in South Pacific. A steering
      committee comprising a member of WONCA Asia Pacific Regional (APR) council and
      the President of Fiji College of General Practitioners garnered sponsorship from
      Fiji Ministry of Health, WONCA APR and pharmaceutical agencies to organize the
      event in October 2013. This paper describes the processes needed to set up a
      national primary research agenda through the collaborative efforts of local
      stakeholders and external facilitators using a test case in South Pacific.
      METHOD: The setting was a 2-day primary care research workshop in Fiji. The
      steering committee invited a team of three external facilitators from the Asia
      Pacific region to organize and operationalize the workshop. The eventual
      participants were 3 external facilitators, 6 local facilitators, and 29 local
      primary care physicians, academics, and local medical leaders from Fiji and South
      Pacific Islands. Pre-workshop and main workshop programs were drawn up by the
      external facilitators, using participants' input of research topics relating to
      their local clinical issues of interest. Course notes were prepared and
      distributed before the workshop. In the workshop, proposed research topics were
      shortlisted by group discussion and consensus. Study designs were proposed,
      scrutinized, and adopted for further research development. RESULTS: The
      facilitators reviewed the processes in setting the research agenda after the
      workshop and conceived the proposed 6E model. These processes can be grouped for
      easy reference, comprising the pre-workshop stages of "entreat", "enlist",
      "engage", and the workshop stages of "educe", "empower", and "encapsulate".
      CONCLUSION: The 6E model to establish a research agenda is conceptually logical.
      Its feasibility can be further tested in its application in other situation where
      research agenda setting is the critical step to improve the quality of primary
      care.

PMID- 25606022
TI  - "The educating nursing staff effectively (TENSE) study": design of a cluster
      randomized controlled trial.
AB  - BACKGROUND: Challenging behavior exhibited by people with dementia can have
      adverse outcomes, like stress, low morale, low work satisfaction and absenteeism
      for nursing staff in long-term care settings. Training nursing staff to manage
      challenging behavior may reduce its impact. Although much of the research into
      training nursing staff shows methodological limitations, several studies find
      some effect of training programs on knowledge about and on management of
      challenging behavior. Effects on stress or burnout are almost not found.
      METHODS/DESIGN: The TENSE-study is a randomized controlled study on 18 nursing
      home units (9 control, 9 intervention) investigating the effects of a continuous
      educational program for nursing staff about managing challenging behavior.
      Nursing staff of intervention units receive the program, nursing staff of control
      units do not and continue usual care. The primary outcome is stress experienced
      by nursing staff (N = 135). Secondary outcomes are: emotional workload, work
      satisfaction, stress reactions at work and knowledge about challenging behaviour
      of nursing staff; and frequency of challenging behavior, quality of life and
      social engagement of residents (N = 135). Because there are many unknown factors
      influencing the effect of the training, a process evaluation to evaluate sampling
      , implementation- and intervention quality as well as barriers and facilitators
      to implementation will also be included in the analysis. Nursing staff could not
      be blinded to the intervention, but were blinded for the outcomes. DISCUSSION:
      Strengths of this study are the (good) description of the intervention
      complemented by a process evaluation and the tailoring of the intervention to the
      wishes and needs of the nursing homes at any moment during the study. Sustaining
      the effects of the intervention by using follow up sessions is another strength.
      Possible drawbacks may be dropout because of the frailty of the elderly
      population and because nursing staff might move to another job during the study.
      TRIAL REGISTRATION: NTR (Dutch Trial Registration) number NTR3620.

PMID- 25606023
TI  - Exploring intensive care nurses' team performance in a simulation-based emergency
      situation, - expert raters' assessments versus self-assessments: an explorative
      study.
AB  - BACKGROUND: Effective teamwork has proven to be crucial for providing safe care.
      The performance of emergencies in general and cardiac arrest situations in
      particular, has been criticized for primarily focusing on the individual's
      technical skills and too little on the teams' performance of non-technical
      skills. The aim of the study was to explore intensive care nurses' team
      performance in a simulation-based emergency situation by using expert raters'
      assessments and nurses' self-assessments in relation to different intensive care
      specialties. METHODS: The study used an explorative design based on laboratory
      high-fidelity simulation. Fifty-three registered nurses, who were allocated into
      11 teams representing two intensive care specialties, participated in a
      videotaped simulation-based cardiac arrest setting. The expert raters used the
      Ottawa Crisis Resource Management Global Rating Scale and the first part of the
      Mayo High Performance Teamwork Scale to assess the teams' performance. The
      registered nurses used the first part of the Mayo High Performance Teamwork Scale
      for their self-assessments, and the analyses used were Chi-square tests, Mann
      Whitney U tests, Spearman's rho and Intraclass Correlation Coefficient Type III.
      RESULTS: The expert raters assessed the teams' performance as either advanced
      novice or competent, with significant differences being found between the teams
      from different specialties. Significant differences were found between the expert
      raters' assessments and the registered nurses' self-assessments. CONCLUSIONS:
      Teams of registered nurses representing specialties with coronary patients
      exhibit a higher competence in non-technical skills compared to team performance
      regarding a simulated cardiac arrest. The use of expert raters' assessments and
      registered nurses' self-assessments are useful in raising awareness of team
      performance with regard to patient safety.

PMID- 25606024
TI  - Characteristics of being hospitalized as a child with a new diagnosis of type 1
      diabetes: a phenomenological study of children's past and present experiences.
AB  - BACKGROUND: Our understanding of children and childhood has changed over the last
      few decades, which may have an impact on children's conditions in hospitals.
      Children's rights have been strengthened by the "Convention on the Rights of the
      Child" and ward regulations. The aim of this Norwegian study was to identify
      potential characteristics of children's lived experience of being hospitalized
      diagnosed with type 1 diabetes today and from a retrospective view in the period
      1950-1980, despite the many obvious external changes. METHODS: This study
      presents a further analysis of data from two previous phenomenological studies.
      The first had a retrospective perspective, and the second assumed a contemporary
      perspective. Twelve adults and nine children who had been hospitalized for newly
      diagnosed type 1 diabetes at the age of approximately 6-12 years old
      participated. The adults relayed narratives from their childhood memories through
      interviews, and the study with the children was designed as a combination of
      observations, in-depth interviews, and photographs. A hermeneutic
      phenomenological method was used in the analysis. RESULTS: The analysis revealed
      a meaning structure that described a tension between vulnerability and agency in
      the experiences of being hospitalized as a child, both past and present. The
      experiences may further be characterized as alienation versus recognition and as
      passivity versus activity, relating to both the hospital environment and the
      illness. CONCLUSIONS: To a greater extent than ever, children today tend to
      experience themselves as active and competent individuals who can manage their
      own illness. Previously, children seemed to experience themselves as more
      vulnerable and less competent in relationship to their environment and illness.
      Presently, as before, children appear to desire involvement in their illness;
      however, at the same time, they prefer to share responsibility with or hand over
      responsibility to adults. However, living with diabetes was and remains
      demanding, and it affects children's lifeworld. Balancing the children's
      vulnerability and agency seems to be the best way to care for children in
      hospitals. In this article, we thus argue for a lifeworld-led approach when
      caring for hospitalized children, paying attention to both their vulnerability
      and agency.

PMID- 25606025
TI  - Lipopolysaccharide responsiveness in vocal fold fibroblasts.
AB  - BACKGROUND: Vocal fold fibroblast's (VFF) strategic location in the lamina
      propria and their ability to respond to external stimuli by producing
      inflammatory molecules suggest their possible direct involvement in innate
      immunity. Toll-like receptors (TLRs) are an essential signaling component to this
      response, as they allow for recognition of various microorganisms, leading to
      subsequent induction of pro-inflammatory genes. The objective of this study was
      to elucidate the role of VFF in the host immune response and subsequent influence
      on inflammatory cytokine secretion. METHODS: VFF derived from polyp, scar, and
      normal tissue were treated with 5 MUg/ml lipopolysaccharide (LPS). TLR1 through
      9, CD14, and MD-2 were measured during stable conditions by polymerase chain
      reaction (PCR). Expression of TLR4 and IL-1R type-1 genes were quantified after
      24 hrs LPS stimulation by reverse transcription-PCR. LPS responsiveness was
      determined by NF-kappaB nuclear translocation as measured by subunit p65
      expression in nucleus with immunocytochemistry. Downstream effects were confirmed
      with immunoassay measuring IL-8 concentrations in supernatant after 8 hrs.
      RESULTS: All VFFs constitutively expressed TLR1 to 6, TLR9, CD14, and MD-2 mRNA.
      Polyp VFF exhibited significantly higher TLR4 transcript levels (p < 0.001) in
      comparison to scar and normal VFF. LPS stimulated scar and polyp VFF exhibited
      increased levels of p65 in the nucleus (p < 0.01) and secreted greater IL-8
      protein (p < 0.0001) compared to normal VFF. CONCLUSION: VFF constitutively
      express genes for the receptors essential to the host immune response. Scar and
      polyp VFF produced greater LPS responsiveness resulting in over-activated
      inflammatory patterns. These findings support VFF role in the pathogenesis of
      inflammatory vocal fold disorders and suggests their presence in the wound bed
      could lead to chronic inflammation.

PMID- 25606026
TI  - The histone deacetylase Hdac1 regulates inflammatory signalling in intestinal
      epithelial cells.
AB  - BACKGROUND: It has recently been found that both nuclear epithelial-expressed
      histone deacetylases Hdac1 and Hdac2 are important to insure intestinal
      homeostasis and control the mucosal inflammatory response in vivo. In addition,
      HDAC inhibitors modulate epithelial cell inflammatory responses in cancer cells.
      However, little is known of the specific role of different HDAC, notably Hdac1,
      in the regulation of inflammatory gene expression in intestinal epithelial cells
      (IEC). METHODS: We investigated the role of Hdac1 in non-transformed IEC-6 rat
      cells infected with lentiviral vectors expressing specific Hdac1 shRNAs, to
      suppress Hdac1 expression. Proliferation was assessed by cell counting.
      Deacetylase activity was measured with a colorimetric HDAC assay. Cells were
      treated with IL-1beta and/or the JQ1 bromodomain acetyl-binding inhibitor.
      Nuclear protein levels of Hdac1, Hdac2, phosphorylated or unphosphorylated NF
      kappaB p65 or C/EBPbeta, and NF-kappaB p50 and actin were determined by Western
      blot. Chemokine and acute phase protein expression was assessed by semi
      quantitative RT-PCR analysis. Secreted cytokine and chemokine levels were
      assessed with a protein array. Chromatin immunoprecipitation experiments were
      done to assess RNA polymerase II recruitment. RESULTS: Reduced Hdac1 protein
      levels led to Hdac2 protein increases and decreased cell proliferation. Hdac1
      depletion prolonged nuclear IL-1beta-induced phosphorylation of NF-kappaB p65
      protein on Ser536 as opposed to total p65, and of C/EBPbeta on Ser105. In
      addition, semi-quantitative RT-PCR analysis revealed three patterns of expression
      caused by Hdac1 depletion, namely increased basal and IL-1beta-stimulated levels
      (Hp, Kng1), increased IL-1beta-stimulated levels (Cxcl2) and decreased basal
      levels with normal IL-1beta induction levels (Ccl2, Ccl5, Cxcl1, C3). Secreted
      cytokine and chemokine measurements confirmed that Hdac1 played roles both as an
      IL-1beta signalling repressor and activator. Hdac1 depletion did not alter the
      JQ1 dependent inhibition of basal and IL-1beta-induced inflammatory gene
      expression. Hdac1 depletion led to decreased basal levels of RNA polymerase II
      enrichment on the Ccl2 promoter, as opposed to the Gapdh promoter, correlating
      with decreased Ccl2 basal mRNA expression. CONCLUSIONS: Hdac1 is a major nuclear
      HDAC controlling IL-1beta-dependent inflammatory response in IEC, notably by
      regulating gene-specific transcriptional responses. Hdac1 may be important in
      restricting basal and inflammatory-induced gene levels to defined ranges of
      expression.

PMID- 25606028
TI  - Within-District Effects of Catholic Schooling on 12th Grad Math Achievement.
AB  - Using a propensity score matching method and regression modeling based on the
      2002 Education Longitudinal Study, this study found a significant Catholic school
      effect on mathematics achievement among those 12th graders who were least likely
      to attend Catholic school. This result is evident within-districts after we used
      the School District Demographics System map data to locate Catholic schools
      within school district boundaries. Furthermore, the Catholic school effects were
      statistically significant for students in districts that allowed publicly funded
      private education.

PMID- 25606027
TI  - An approach to prioritization of medical devices in low-income countries: an
      example based on the Republic of South Sudan.
AB  - BACKGROUND: Efficient and evidence-based medical device and equipment
      prioritization is of particular importance in low-income countries due to
      constraints in financing capacity, physical infrastructure and human resource
      capabilities. METHODS: This paper outlines a medical device prioritization method
      developed in first instance for the Republic of South Sudan. The simple algorithm
      offered here is a starting point for procurement and selection of medical devices
      and can be regarded as a screening test for those that require more labour
      intensive health economic modelling. CONCLUSIONS: A heuristic method, such as the
      one presented here, is appropriate for reaching many medical device
      prioritization decisions in low-income settings. Further investment and
      purchasing decisions that cannot be reached so simply require more complex health
      economic modelling approaches.

PMID- 25606029
TI  - Cystic lymphangioma of the chest wall: a case report.
AB  - Cystic lymphangioma is a congenital cystic malformation that occurs mostly in
      children. While it is mainly found in the cervix, cases in the chest wall are
      very rare. We report a case of cystic lymphangioma found in the chest wall of a 2
      month-old girl. The patient was noted to have a tumor in the left chest wall at
      birth. Since it gradually increased in size, the patient was referred to our
      department. Transillumination and ultrasonography showed a cystic lesion in the
      left chest. Surgical resection was performed in one step. Histopathological
      examination showed a cystic lymphangioma. 

PMID- 25606030
TI  - A 25-year-old woman with type 2 diabetes and liver disease.
AB  - A 25-year-old female nurse was referred to our diabetes outpatient clinic with
      poorly controlled type 2 diabetes, obesity and elevated liver function tests
      (LFTs). Following a liver biopsy she was diagnosed with non-alcoholic
      steatohepatitis (NASH) and liver fibrosis. Treatment with subcutaneous injections
      of the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was
      initiated. After 46 weeks of treatment the patient had lost 16 kg, glycemic
      control was excellent and LFTs had normalized. Repeat liver biopsy and ultrasound
      showed reduction in hepatic fat content and inflammatory cells. The biopsy no
      longer fulfilled the criteria for NASH. The liver biopsies did not express
      hepatic GLP-1Rs using quantitative polymerase chain reaction. Our case suggests
      that liraglutide may benefit patients with NASH. 

PMID- 25606031
TI  - Variations in the Blood Phenytoin Levels during Long-Term Combined Treatment with
      S-1 and Phenytoin.
AB  - Although combination therapy with the oral fluoropyrimidine anticancer drug S-1
      and the anticonvulsant phenytoin (PHT) is known to increase blood levels of PHT
      and the risk of intoxication, reports on long-term monitoring of blood levels of
      PHT during combined S-1 and PHT treatment and a thorough understanding of their
      interaction are lacking. This report aims to describe interactive effects of S-1
      and PHT through long-term therapeutic drug monitoring of PHT. A 72-year-old male
      had been prescribed oral PHT (130 mg/day) for over 20 years and started receiving
      S-1 therapy (80 mg/day for 4 weeks, followed by a 2-week rest) as postoperative
      adjuvant chemotherapy for gastric cancer. The blood PHT level was continuously
      monitored. Prior to receiving S-1, the patient's blood PHT concentration was 6.0
      MUg/ml, but it increased during S-1 therapy, reaching 22.9 MUg/ml on day 84
      (during a rest period of second cycle S-1 therapy). After reducing his PHT dosage
      to 100 mg/day, it never reached toxic levels (4.0-10.4 MUg/ml). It was difficult
      to keep blood PHT concentrations constant because of the time lag between the
      period of combined use of S-1 and PHT and the timing of manifestation and
      disappearance of the drug interaction. The DIPS probability scale indicated a
      highly probable interaction between S-1 and PHT. We conclude that, when S-1 and
      PHT are used concurrently, occurrence and disappearance time of their interaction
      need to be predicted to maintain an effective and safe PHT concentration. 

PMID- 25606032
TI  - Hepatocellular carcinoma in a noncirrhotic liver after long-term use of danazol
      for hereditary angioedema.
AB  - We report a 57-year-old male who was treated with high-dose danazol for
      hereditary angioedema for more than 30 years; he developed hepatocellular
      carcinoma in the absence of cirrhosis. Despite surgical resection, he had a
      recurrence and received sorafenib, but had a poor skin tolerance. Such tumors
      arising after danazol are infrequent, and this case is highly unique due to the
      minor lesions found on the liver. 

PMID- 25606033
TI  - Intractable Facial Pain and Numb Chin due to Metastatic Esophageal
      Adenocarcinoma.
AB  - The etiologies of facial pain are innumerable, thus facial pain misdiagnosis and
      resultant mismanagement is common. Numb chin syndrome presents with hypoesthesia
      and/or anesthesia in the dermatomal distribution of the inferior alveolar or the
      mental nerve. In this case report, we will discuss a case of intractable facial
      pain in a 57-year-old male with a history of esophageal adenocarcinoma who was
      initially misdiagnosed and treated as trigeminal neuralgia. During clinical
      examination, the loss of sensation in the inferior alveolar nerve distribution
      was identified and led to the diagnosis of mandibular metastasis. The details of
      the clinical presentation will be discussed in the context of accurate
      identification and diagnosis. Focal radiation to the metastatic location along
      with sphenopalatine ganglion radiofrequency ablation and medication management
      provided significant pain relief. This case report provides additional
      information to the current medical knowledge and it enhances the clinical
      vigilance of the clinicians when they encounter similar cases. We concluded that
      patients with a history of neoplasms who present with atypical symptoms of facial
      pain should undergo further investigation with advanced imaging. Targeted
      treatment based on an accurate diagnosis is the foundation of pain management. 

PMID- 25606034
TI  - Bilateral traumatic globe luxation with optic nerve transection.
AB  - PURPOSE: The purpose of this study was to document clinical findings and
      management of a patient with bilateral globe luxation and optic nerve
      transection. MATERIALS AND METHODS: A 25-year-old female patient was admitted to
      the emergency department with bilateral traumatic globe luxation following a
      motor vehicle accident. RESULTS: Visual acuity testing showed no light
      perception. The right pupil was dilated and bilaterally did not react to light.
      The globes were bilaterally intact. A computed tomography scan revealed Le Fort
      type II fractures, bilateral optic nerve transection and disruption of all
      extraocular muscles. The globes of the patient were bilaterally reduced into the
      orbit. However, the patient developed phthisis bulbi in the right eye at month 3.
      CONCLUSION: Globe luxation presents a dramatic clinical picture, and may lead to
      the development of severe complications due to the concomitance of complete optic
      nerve dissection and multiple traumas. Even if the luxated globe is repositioned
      into the orbit, there is still an increased risk of the development of phthisis
      due to ischemia.

PMID- 25606035
TI  - Botulinum toxin therapy in congenital blepharospasm.
AB  - Botulinum toxin injections are the treatment of choice for the management of
      essential blepharospasm in adults. No cases of congenital blepharospasm have been
      described in the literature so far, and no cases of botulinum toxin injection in
      an infant have been reported. A 4-week-old girl was referred to our department
      with absent eye opening and spasmodically closed eyes. Pregnancy and delivery had
      been normal. A neuropediatric examination did not reveal useful findings. A
      periorbital injection of botulinum toxin was performed at the age of 2 months to
      prevent deprivation amblyopia. Four days later, clearly visible bilateral eye
      opening and commencement of eye contact were observed. At the age of 3 years, her
      eyelids remain open and no side effects of botulinum toxin therapy have occurred.

PMID- 25606036
TI  - Unilateral angle-closure glaucoma with ciliochoroidal effusion after the
      consumption of cannabis: a case report.
AB  - A 35-year-old male patient, diagnosed with acute angle-closure glaucoma, did not
      improve despite intensive treatment with antiglaucoma medications. Ultrasound
      biomicroscopy revealed a ciliochoroidal effusion. Due to his past history of drug
      abuse, a urine test was analyzed and found to be positive for cannabis. After
      topical cycloplegia and oral steroid therapy, his symptoms improved
      substantially. The present case highlights the role of ultrasound biomicroscopy
      in evaluating patients with acute angle-closure glaucoma and the role of cannabis
      abuse in the development of ciliochoroidal effusion. 

PMID- 25606037
TI  - Conjunctival follicular lymphoma after treatment for invasive squamous cell
      carcinoma.
AB  - BACKGROUNDS/AIMS: The authors describe the case of a 79-year-old Caucasian woman
      who presented an ocular adnexal lesion as the first clinical manifestation of a
      systemic follicular lymphoma, highlighting the clinicopathological features of
      this rare entity and its potential to be misdiagnosed as marginal zone lymphoma
      of the mucosa-associated lymphoid tissue. METHODS: Conjunctival impression
      cytology was performed for a rapid initial diagnosis of lymphoma, and subsequent
      histopathological and immunohistochemical studies were carried out for its
      confirmation and to identify the best therapeutic regimen. RESULTS: After the
      initial presentation and diagnosis, she was submitted to complete clinical
      evaluation; confluent retroperitoneal lymphadenopathy was detected through
      abdominal computed tomography, characterizing clinical stage III. CONCLUSION:
      Awareness of this lymphoma is important when making a diagnosis of ocular adnexal
      lymphoid neoplasms for its appropriate evaluation and management.

PMID- 25606038
TI  - Bilateral macular edema in a patient treated with tamoxifen: a case report and
      review of the literature.
AB  - We present a case of a 41-year-old female patient with progressive bilateral
      visual loss. On examination, her best corrected visual acuity (BCVA) in her right
      eye was 3/10 and her BCVA in her left eye was 2/10. Fundus and optical coherence
      tomography examination revealed severe bilateral macular edema. She had been
      diagnosed with breast cancer 6 years ago and was receiving tamoxifen at a dosage
      of 20 mg/day ever since. Tamoxifen therapy was discontinued, and the patient
      received 250 mg of acetazolamide three times a day for a period of 1 month. Both
      foveae regained their normal contour within 2 months, and her vision was restored
      to 10/10 BCVA 3 months later. To our knowledge, this is the first case reported
      where bilateral intraretinal macular edema is the only retinal manifestation in a
      patient on oral tamoxifen. 

PMID- 25606039
TI  - Incomplete vitreomacular traction release using intravitreal ocriplasmin.
AB  - PURPOSE: To report the clinical course of our first 7 consecutive patients
      treated with intravitreal ocriplasmin (Jetrea((r))). METHODS: Retrospective case
      series of the first 7 patients treated with ocriplasmin between January and
      December 2013 at an academic tertiary care center. RESULTS: The average age was
      78.4 years (range: 63-92). Five patients were pseudophakic and 2 patients were
      phakic in the injected eye. The median baseline visual acuity (VA) was 20/60
      (range: 20/25 to 20/200). The median 1-month postinjection VA was 20/70, with a
      mean loss of 2 lines of VA among all patients. None of the patients had complete
      resolution of their vitreomacular traction or macular hole at 1 month of follow
      up. Three patients had subsequent pars plana vitrectomy and membrane peeling
      surgery. The mean follow-up period for those who did not undergo vitrectomy was 9
      months (range: 1-13). One patient with known ocular hypertension had an increase
      in intraocular pressure requiring topical pressure-lowering eyedrops. There were
      no cases of postinjection uveitis, endophthalmitis, retinal tears, or retinal
      detachment. CONCLUSIONS: While ocriplasmin may be a viable pharmacological agent
      for vitreolysis, we present a series of patients that all had incomplete
      resolution of vitreomacular traction with and without full-thickness macular
      hole. There was an associated reduction in VA after ocriplasmin treatment at 1
      month of follow-up. Careful analysis of the vitreoretinal interface and comorbid
      eye conditions is required to optimize outcome success with ocriplasmin.

PMID- 25606040
TI  - Choroidal nevus in an eye with polypoidal choroidal vasculopathy.
AB  - PURPOSE: To report an eye with polypoidal choroidal vasculopathy (PCV) and a
      choroidal nevus. METHODS: This is an observational case report. RESULTS: A
      healthy 69-year-old woman was referred to the Osaka University Hospital with a
      diagnosis of a macular tumor. She complained of having distorted vision in her
      left eye. The medical history of the patient was unremarkable. At the initial
      examination, her best-corrected visual acuity (BCVA) was 20/20 in both eyes, and
      the intraocular pressure was 18 mm Hg in both eyes. A slit-lamp examination
      showed no abnormalities in the anterior segment of both eyes and a fundus
      examination of the left eye showed a slightly elevated juxtafoveal chorioretinal
      lesion and polyp-like reddish-orange lesions. The juxtafoveal choroidal lesion
      was located beneath a choroidal neovascularization (CNV). An optical coherence
      tomography confirmed CNV with pigment epithelial detachment (PED). Fluorescein
      angiography showed juxtafoveal hyperfluorescence due to CNV. Indocyanine green
      angiography demonstrated a branching choroidal vascular network that resembled
      polypoidal lesions. A fundus autofluorescence showed a mosaic pattern and a
      slight hyperautofluorescence at the CNV. We diagnosed the patient as having PCV.
      Aflibercept was injected intravitreally because of her PED. After the injection,
      PED improved and her visual acuity remained stable during the 12-month follow-up
      period. CONCLUSIONS: In cases of PCV, FAF images are helpful in determining the
      status of the posterior pole. Intravitreal injections of aflibercept can improve
      PED associated with CNV, and the BCVA will remain stable for at least 12 months.

PMID- 25606041
TI  - Klebsiella pneumoniae Infection: A Virulent Cause of Visual Loss.
AB  - Bacterial endophthalmitis is endogenous in 2-6% of cases and is frequently
      misdiagnosed initially. Klebsiella pneumoniae is being increasingly recognised as
      an aggressive causative organism, and it is particularly prevalent in Asian
      populations. We describe the case of a 71-year-old female of Southeast Asian
      origin with type 2 diabetes mellitus who presented with visual loss secondary to
      bacterial endophthalmitis and concomitant cerebral abscesses. Imaging revealed
      the probable primary source of infection to be a liver abscess. She developed
      retinal detachment and subsequently underwent an evisceration of her right eye. A
      Klebsiella spp. was identified from the eye tissue by 16S rRNA amplification.
      Klebsiella pneumoniae endophthalmitis has a characteristic disease phenotype and
      a particularly aggressive course with poor visual outcomes observed in most
      cases. This case highlights the risks of metastatic infection including bacterial
      endophthalmitis in association with Klebsiella infection. 

PMID- 25606042
TI  - Gaps between Global Guidelines and Local Practices in CKD-MBD.
AB  - The term 'chronic kidney disease-mineral bone disorder' (CKD-MBD) is a new term
      that, in contrast to the old term 'renal osteodystrophy', implies a systemic
      syndrome associated with cardiovascular morbidity and mortality. This new
      terminology is in line with previous studies that show elevated serum calcium,
      phosphorus, and parathyroid hormone (PTH) levels associated with increased
      cardiovascular and all-cause mortality. In order to improve outcomes in patients
      with CKD-MBD, many countries have developed clinical practice guidelines.
      Globally, the Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney
      Disease: Improving Global Outcomes (KDIGO) guidelines are the most commonly used.
      However, whether these global guidelines can be successfully implemented on a
      local level needs to be studied. Differences in medical care and social factors
      between countries may limit the generalizability of global guidelines. Reports
      from the Korean registry and the Dialysis Outcomes and Practice Patterns Study
      (DOPPS) suggest that many dialysis patients are not within the target ranges
      recommended by the KDOQI and KDIGO guidelines for serum calcium, phosphorus, and
      PTH, suggesting gaps between global guidelines and local practices. Clinical
      studies with Korean CKD-MBD patients are necessary to compare Korean practices
      and outcomes to those suggested by global guidelines and to determine the target
      serum mineral levels associated with the best local outcomes. 

PMID- 25606043
TI  - How do We Manage Coronary Artery Disease in Patients with CKD and ESRD?
AB  - Chronic kidney disease (CKD) has been shown to be an independent risk factor for
      cardiovascular events. In addition, patients with pre-dialysis CKD appear to be
      more likely to die of heart disease than of kidney disease. CKD accelerates
      coronary artery atherosclerosis by several mechanisms, notably hypertension and
      dyslipidemia, both of which are known risk factors for coronary artery disease.
      In addition, CKD alters calcium and phosphorus homeostasis, resulting in
      hypercalcemia and vascular calcification, including the coronary arteries.
      Mortality of patients on long-term dialysis therapy is high, with age-adjusted
      mortality rates of about 25% annually. Because the majority of deaths are caused
      by cardiovascular disease, routine cardiac catheterization of new dialysis
      patients was proposed as a means of improving the identification and treatment of
      high-risk patients. However, clinicians may be uncomfortable exposing
      asymptomatic patients to such invasive procedures like cardiac catheterization,
      thus noninvasive cardiac risk stratification was investigated widely as a more
      palatable alternative to routine diagnostic catheterization. The effective
      management of coronary artery disease is of paramount importance in uremic
      patients. The applicability of diagnostic, preventive, and treatment modalities
      developed in nonuremic populations to patients with kidney failure cannot
      necessarily be extrapolated from clinical studies in non-kidney failure
      populations. Noninvasive diagnostic testing in uremic patients is less accurate
      than in nonuremic populations. Initial data suggest that dobutamine
      echocardiography may be the preferred diagnostic method. PCI with stenting is a
      less favorable alternative to CABG, however, it has a faster recovery time,
      reduced invasiveness, and no overall mortality difference in nondiabetic and non
      CKD patients compared with CABG. CABG is associated with reduced repeat
      revascularizations, greater relief of angina, and increased long term survival.
      However, CABG is associated with a higher incidence of post-operative risks. The
      treatment chosen for each patient should be an individualized decision based upon
      numerous risk factors. CKD is associated with higher rates of CAD, with 44% of
      all-cause mortality attributable to cardiac disease and about 20% from acute MI.
      Optimal treatment including aggressive lifestyle modifications and concomitant
      medical therapy should be implemented in all patients to maximize benefits from
      either PCI or CABG. Future prospective randomized controlled trials with newer
      second or third generation DES and bioabsorbable DES are necessary to determine
      if PCI may be non-inferior to CABG in the future. 

PMID- 25606045
TI  - Effect of dialysate sodium concentration on sodium gradient and hemodialysis
      parameters.
AB  - This retrospective study was performed to determine the ranges of the sodium
      gradient (SG) between the dialysate sodium concentration (DNa) and serum sodium
      concentration (SNa) in hemodialysis (HD) patients and to examine the
      relationships between HD parameters over a 1 year period. Fifty-five clinically
      stable HD patients, who had been on HD >2 years were enrolled. Monthly HD
      [ultrafiltration (UF) amount, systolic blood pressure (SBP), frequency of
      intradialytic hypotension (IDH)] and laboratory data were collected and 12-month
      means were subjected to analysis. The SG was calculated by subtracting SNa from
      prescribed DNa. Mean SG values were 1.5+/-3.3 (range -5.6~9.1). SG was positively
      related to DNa and the frequency of IDH. A higher SG was associated with larger
      UF amounts and SBP reduction during HD. The percentages of patients with a SG
      >=3mEq/L increased as DNa increased. On the other hand, SG was not found to be
      associated with SNa or pre-HD SBP. DNa appears to cause a significant increase in
      SG, and this seems to be related to HD parameters, such as, UF amount and IDH. 

PMID- 25606044
TI  - Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment
      Strategies.
AB  - Cisplatin is one of the most widely used and highly effective drug for the
      treatment of various solid tumors; however, it has dose-dependent side effects on
      the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and
      clinically important toxicity. Numerous studies have demonstrated that several
      mechanisms, including oxidative stress, DNA damage, and inflammatory responses,
      are closely associated with cisplatin-induced nephrotoxicity. Even though the
      establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics
      and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is
      still high, occurring in approximately one-third of patients who have undergone
      cisplatin therapy. Therefore it is imperative to develop treatments that will
      ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of
      cisplatin-induced renal toxicity and the new strategies for protecting the
      kidneys from the toxic effects without lowering the tumoricidal activity. 

PMID- 25606046
TI  - Epidermal Proteinase-Activated Receptor-2 Expression is Increased in End-Stage
      Renal Disease Patients with Pruritus: A Pilot Study.
AB  - Uremic pruritus is a common problem in patients with end-stage renal disease
      (ESRD), but the underlying mechanisms are not yet fully understood. We aimed to
      investigate the association between severity of uremic pruritus and cutaneous
      serine protease activity, as well as proteinase-activated receptor-2 (PAR-2)
      expression. Twelve ESRD patients with pruritus, 4 ESRD patients without pruritus,
      and 6 healthy controls were enrolled. Skin biopsies were obtained from the
      abdomen. Protease activity and PAR-2 expression in the epidermis were examined by
      in situ zymography and confocal laser microscopy, respectively. All ESRD patients
      presented more pronounced cutaneous protease activity compared with that in
      healthy controls. The skin samples from the patients with pruritus showed higher
      protease activity than either nonpruritic ESRD patients or healthy controls. The
      epidermis in all samples of ESRD patients presented higher immunoreactivity
      against PAR-2 versus those of healthy controls. In addition, correlation analysis
      between PAR-2 expression and VAS pruritus scores showed a significant positive
      correlation. Our data suggests that levels of serine protease and PAR-2
      expression could play important roles in the pathogenesis of uremic pruritus. 

PMID- 25606047
TI  - Effect of bicarbonate supplementation on renal function and nutritional indices
      in predialysis advanced chronic kidney disease.
AB  - Current practice guidelines recommend alkali therapy in patients with chronic
      kidney disease (CKD) and metabolic acidosis to prevent complications. This study
      aims to investigate the effect of oral sodium bicarbonate supplementation on the
      progression of renal function and nutritional indices in patients with
      predialysis advanced CKD. Forty patients with predialysis stage 5 CKD(estimated
      glomerular filtration rate, eGFR <15mL/min per 1.73m(2)) and 40 patients with
      stage 4 CKD (eGFR 15 to 30mL/min per 1.73m(2)) who had a total CO2 less than
      22mEq/L were assigned into the bicarbonate treatment group or control group for
      12 months. In stage 4 CKD, there were significant differences in the changes of
      eGFR during the study between the treatment group and the control group (-2.30+/
      4.49 versus -6.58+/-6.32mL/min/1.73m(2), p<0.05). However, in stage 5 CKD, there
      were no significant differences in the change of eGFR during the study between
      the two groups (-2.10+/-2.06 versus -3.23+/-1.95mL/min/1.73 m(2)).There were no
      significant differences in the changes of nutritional indices such as albumin,
      prealbumin, transferrin, total lymphocyte count (TLC), and Ondodera's prognostic
      nutritional index (OPNI) during the study between the two groups. In stage 5 CKD,
      there were significant differences in the changes of TLC and OPNI between the two
      groups. In conclusion, our results demonstrate that bicarbonate supplementation
      slows the rate of decline of renal function in stage 4 CKD and improves
      nutritional indices in stage 5 CKD. Alkali therapy in advanced CKD may have
      beneficial effect on renal function and malnutrition. 

PMID- 25606048
TI  - Genetically diverse mice are novel and valuable models of age-associated
      susceptibility to Mycobacterium tuberculosis.
AB  - BACKGROUND: Tuberculosis, the disease due to Mycobacterium tuberculosis, is an
      important cause of morbidity and mortality in the elderly. Use of mouse models
      may accelerate insight into the disease and tests of therapies since mice age
      thirty times faster than humans. However, the majority of TB research relies on
      inbred mouse strains, and these results might not extrapolate well to the
      genetically diverse human population. We report here the first tests of M.
      tuberculosis infection in genetically heterogeneous aging mice, testing if old
      mice benefit from rapamycin. FINDINGS: We find that genetically diverse aging
      mice are much more susceptible than young mice to M. tuberculosis, as are aging
      human beings. We also find that rapamycin boosts immune responses during primary
      infection but fails to increase survival. CONCLUSIONS: Genetically diverse mouse
      models provide a valuable resource to study how age influences responses and
      susceptibility to pathogens and to test interventions. Additionally, surrogate
      markers such as immune measures may not predict whether interventions improve
      survival.

PMID- 25606049
TI  - Medical work assessment in German hospitals: a study protocol of a movement
      sequence analysis (MAGRO-MSA).
AB  - BACKGROUND: Medical doctors are essential for the German public and occupational
      health system. They ensure the productivity of German society by enabling people
      to regain and recover their health. That is why the physicians' health and hence
      their productivity require special attention. Musculoskeletal disorders have a
      high prevalence in this work area. As a consequence, movement sequences, range of
      motions, and body postures of physicians in the course of the working day are in
      focus of this research project. METHODS: For this investigation 21 male or female
      junior physicians of various conservative medical disciplines will be covered.
      Data will be collected over one working day (approx. 9 hours). The CUELA system
      attached to the test person's body detects body posture and/or movements. This
      biomechanical measurement system ensures a locomotor and posture analysis that
      includes movement sequences, movement intensity, and range of motions to qualify
      the work tasks. For data analysis intra- and inter-professional comparisons are
      chosen. CONCLUSIONS: Working movement sequence analysis of physicians by means of
      the CUELA system is exclusive and novel in its focus. Up to now, knowledge of the
      working tasks of medical doctors has only been acquired by real-time observation
      approaches to work activity. In addition to this method of analysis, the CUELA
      system is able to record quantified biomechanical data about musculoskeletal
      loads of ordinary working tasks. Workloads and activities of physicians can be
      improved by ergonomic work design to reduce musculoskeletal disorders by
      utilizing the data collected. The healthcare system in Germany will thus be
      optimized by improving medical doctors' health. Consequently, MAGRO-MSA will also
      be used for other healthcare professions such as nurses and physicians
      assistants.

PMID- 25606050
TI  - Challenges of disseminating clinical practice guidelines in a weak health system:
      the case of HIV and infant feeding recommendations in Tanzania.
AB  - BACKGROUND: Clinical guidelines aim to improve patient outcomes by providing
      recommendations on appropriate healthcare for specific clinical conditions.
      Scientific evidence produced over time leads to change in clinical guidelines,
      and a serious challenge may emerge in the process of communicating the changes to
      healthcare practitioners and getting new practices adopted. There is very little
      information on the major barriers to implementing clinical guidelines in low
      income settings. Looking at how continual updates to clinical guidelines within a
      particular health intervention are communicated may shed light on the processes
      at work. The aim of this paper is to explore how the content of a series of
      diverging infant feeding guidelines have been communicated to managers in the
      Prevention of Mother to Child Transmission of HIV Programme (PMTCT) with the aim
      of generating knowledge about both barriers and facilitating factors in the
      dissemination of new and updated knowledge in clinical guidelines in the context
      of weak healthcare systems. METHODS: A total of 22 in-depth interviews and two
      focus group discussions were conducted in 2011. All informants were linked to the
      PMTCT programme in Tanzania. The informants included managers at regional and
      district levels and health workers at health facility level. RESULTS: The
      informants demonstrated partial and incomplete knowledge about the
      recommendations. There was lack of scientific reasoning behind various infant
      feeding recommendations. The greatest challenges to the successful communication
      of the infant feeding guidelines were related to slowness of communication,
      inaccessible jargon-ridden English language in the manuals, lack of summaries,
      lack of supportive supervision to make the guidelines comprehensible, and the
      absence of a reading culture. CONCLUSION: The study encountered substantial gaps
      in knowledge about the diverse HIV and infant feeding policies. These gaps were
      partly related to the challenges of communicating the clinical guidelines. There
      is a need for caution in assuming that important changes in guidelines for
      clinical practice can easily be translated to and implemented in local programme
      settings, not least in the context of weak healthcare systems.

PMID- 25606052
TI  - Effects of methylphenidate in children with attention deficit hyperactivity
      disorder: a near-infrared spectroscopy study with CANTAB(r).
AB  - BACKGROUND: A wide range of evidence supports the methylphenidate (MPH)-induced
      enhancement of prefrontal cortex (PFC) functioning and improvements in behavioral
      symptoms in patients with attention deficit hyperactivity disorder (ADHD).
      Although working memory (WM) has been hypothesized to be impaired in patients
      with ADHD, no pharmacological studies have examined visuospatial WM (VSWM) with
      near-infrared spectroscopy (NIRS). STUDY AIM: The present study was designed to
      investigate the acute effects of MPH on neuropsychological performance and
      hemodynamic activation in children with ADHD during VSWM tasks. METHODS: The
      subject group included 10 boys and 1 girl previously diagnosed with ADHD. Two
      VSWM tasks of differing degrees of difficulty were conducted. This is the first
      study on the pharmacological effects of MPH in children with ADHD to evaluate
      hemodynamic responses in the PFC with simultaneous NIRS. RESULTS: No significant
      differences were found in the scores for both spatial working memory (SWM) and
      score of spatial span (SSP) tasks between the MPH-off and MPH-on conditions.
      However, a significant MPH-effect on changes in oxy-hemoglobin levels in the PFC
      was found only in the SWM task. CONCLUSION: These findings suggest that PFC
      activation might be affected by MPH, depending on the degree of difficulty of the
      particular task. Although the MPH-induced change on behavior may or may not be
      obvious, NIRS measurements might be useful for assessing the psychological
      effects of MPH even when performance changes were not observed in the cognitive
      tasks.

PMID- 25606053
TI  - Comprehensive utilization of waste hemicelluloses during ethanol production to
      increase lactic acid yield: from pretreatment to fermentation.
AB  - BACKGROUND: Reducing the cost of producing cellulosic ethanol is essential for
      the industrialization of biorefinery. Several processes are currently under
      investigation, but few of these techniques are entirely satisfactory in terms of
      competitive cost or environmental impact. In this study, a new ethanol and lactic
      acid (LA) coproduction is proposed. The technique involved addition of waste
      alkaline peroxide pretreated hydrolysate (mainly LA and hemicelluloses) to the
      reaction mixture after ethanol fermentation (mainly LA and xylose) to reduce the
      ethanol production cost. RESULTS: The following processes were investigated to
      optimize LA production: no addition of hemicelluloses or hydrolysate, addition of
      recycled hemicelluloses, and addition of concentrated hydrolysate. The addition
      of concentrated hydrolysate at 48 hours, which resulted in a maximum LA
      concentration of 22.3 g/L, was the most environment-friendly and cost-effective
      process. After the improved fermentation, 361 mg LA and 132 mg ethanol were
      produced from 1 g of raw poplar wood. That is, the production of one gallon of
      ethanol produced $9 worth of LA. CONCLUSIONS: The amount of LA produced from the
      pretreated hydrolysate and reaction mixture after ethanol fermentation cannot be
      underestimated. The recovery of hydrolysate rich in LA and hemicelluloses (or
      xylose) significantly improved LA yield and further reduced the ethanol
      production cost.

PMID- 25606051
TI  - Protective mechanisms of medicinal plants targeting hepatic stellate cell
      activation and extracellular matrix deposition in liver fibrosis.
AB  - During chronic liver injury, hepatic stellate cells (HSC) are activated and
      proliferate, which causes excessive extracellular matrix (ECM) deposition,
      leading to scar formation and fibrosis. Medicinal plants are gaining popularity
      as antifibrotic agents, and are often safe, cost-effective, and versatile. This
      review aims to describe the protective role and mechanisms of medicinal plants in
      the inhibition of HSC activation and ECM deposition during the pathogenesis of
      liver fibrosis. A systematic literature review on the anti-fibrotic mechanisms of
      hepatoprotective plants was performed in PubMed, which yielded articles about
      twelve relevant plants. Many of these plants act via disruption of the
      transforming growth factor beta 1 signaling pathway, possibly through reduction
      in oxidative stress. This reduction could explain the inhibition of HSC
      activation and reduction in ECM deposition. Medicinal plants could be a source of
      anti-liver fibrosis compounds. 

PMID- 25606054
TI  - Genetic changes observed in a case of adult pilocytic astrocytoma revealed by
      array CGH analysis.
AB  - BACKGROUND: A palette of copy number changes in a case of adult pilocytic
      astrocytoma analyzed by Array Comparative Genomic Hybridization (aCGH) is
      presented. Pilocytic astrocytomas are specific gliomas that are benign and
      biologically distinct and the molecular mechanisms responsible for their
      development remain unexplained. The aCGH was performed using SurePrint G3 Human
      CGH microarrays 4 * 180 K (Agilent Technologies). To ascertain whether some of
      the aberrations were of constitutive nature, we also analyzed the blood sample
      from the same patient. RESULTS: The result of aCGH analysis demonstrated
      differences in the tumor tissue when compared to normal control on the array and
      also to autologous DNA from patient's blood. The total number of aberrations
      found in our case was 41 including 37 deletions and 4 amplifications. Whole
      chromosomal gains and losses were not observed. Collectively, our results showed
      three deletions and one amplification at 1p, two deletions at 2q, two deletions
      at 4q, two deletion at 5q, two deletions at 7p and two deletions at 7q; there
      were also three deletions at 8q, one deletion at 9p, one deletion at 10p, three
      deletions and one amplification at 10q. Chromosome 11 showed two deletions at
      11p, while there was one deletion at 12p and one at 12q. Four deletions at 14q;
      two deletions at 15q, one amplification at 17q and one deletion at 17q; one
      deletion at 18p, two deletions at 22q and finally one deletion at Xp and one
      deletion and one amplification at Xq. Among the signaling pathways, olfactory
      transduction, Fc gamma R-mediated phagocytosis and p53 signaling pathway showed
      significant enrichment ascertained by gene ontology (GO) analysis using the DAVID
      software. CONCLUSIONS: Our aCGH analysis is bringing subtle genomic alterations
      thus broadening genetic spectrum of adult pilocytic astrocytoma in order to offer
      new molecular biomarkers that will help in diagnostics and therapeutic decision
      making.

PMID- 25606055
TI  - Single gene microdeletions and microduplication of 3p26.3 in three unrelated
      families: CNTN6 as a new candidate gene for intellectual disability.
AB  - BACKGROUND: Detection of submicroscopic chromosomal alterations in patients with
      a idiopathic intellectual disability (ID) allows significant improvement in
      delineation of the regions of the genome that are associated with brain
      development and function. However, these chromosomal regions usually contain
      several protein-coding genes and regulatory elements, complicating the
      understanding of genotype-phenotype correlations. We report two siblings with ID
      and an unrelated patient with atypical autism who had 3p26.3 microdeletions and
      one intellectually disabled patient with a 3p26.3 microduplication encompassing
      only the CNTN6 gene. RESULTS: Two 295.1-kb microdeletions and one 766.1-kb
      microduplication of 3p26.3 involving a single gene, CNTN6, were identified with
      an Agilent 60K array. Another 271.9-kb microdeletion of 3p26.3 was detected using
      an Affymetrix CytoScan HD chromosome microarray platform. The CHL1 and CNTN4
      genes, although adjacent to the CNTN6 gene, were not affected in either of these
      patients. CONCLUSIONS: The protein encoded by CNTN6 is a member of the
      immunoglobulin superfamily and functions as a cell adhesion molecule that is
      involved in the formation of axon connections in the developing nervous system.
      Our results indicate that CNTN6 may be a candidate gene for ID.

PMID- 25606056
TI  - Deciphering the pathogenic consequences of chromosomal aberrations in human
      genetic disease.
AB  - Chromosomal aberrations include translocations, deletions, duplications,
      inversions, aneuploidies and complex rearrangements. They underlie genetic
      disease in roughly 15% of patients with multiple congenital abnormalities and/or
      mental retardation (MCA/MR). In genetic diagnostics, the pathogenicity of
      chromosomal aberrations in these patients is typically assessed based on criteria
      such as phenotypic similarity to other patients with the same or overlapping
      aberration, absence in healthy individuals, de novo occurrence, and protein
      coding gene content. However, a thorough understanding of the molecular
      mechanisms that lead to MCA/MR as a result of chromosome aberrations is often
      lacking. Chromosome aberrations can affect one or more genes in a complex manner,
      such as by changing the regulation of gene expression, by disrupting exons, and
      by creating fusion genes. The precise delineation of breakpoints by whole-genome
      sequencing enables the construction of local genomic architecture and facilitates
      the prediction of the molecular determinants of the patient's phenotype. Here, we
      review current methods for breakpoint identification and their impact on the
      interpretation of chromosome aberrations in patients with MCA/MR. In addition, we
      discuss opportunities to dissect disease mechanisms based on large-scale genomic
      technologies and studies in model organisms. 

PMID- 25606057
TI  - TRIP11-PDGFRB fusion in a patient with a therapy-related myeloid neoplasm with
      t(5;14)(q33;q32) after treatment for acute promyelocytic leukemia.
AB  - BACKGROUND: Therapy-related myeloid neoplasm after treatment for acute
      promyelocytic leukemia (APL) is a relatively infrequent but severe complication.
      Most therapy-related myeloid neoplasms after treatment for APL are classified as
      therapy-related myelodysplastic syndrome or therapy-related acute myeloid
      leukemia. Translocation of 5q31-33, PDGFRB occur rarely in therapy-related
      myeloid neoplasm and there has been two identified PDGFRB partner genes located
      at 14q32, TRIP11 and KIAA1509. RESULTS: The TRIP11-PDGFRB fusion was identified
      in a patient with therapy-related myeloid neoplasm with t(5;14)(q33;q32) after
      treatment of APL using conventional cytogenetics, fluorescence in situ
      hybridization (FISH) and molecular methods. Cytogenetic analysis of the bone
      marrow aspirate revealed 46, XY, t(5;14)(q33;q32) in all 20 analyzed cells. No
      other cytogenetic abnormalities were observed. Break-apart FISH analysis
      demonstrated that rearrangement of PDGFRB at 5q33 was positive in 460 of 500
      cells analyzed, while the PML-RARA rearrangement remained undetectable by RT-PCR.
      Sequencing of RT-PCR products revealed fusion between exon 16 of TRIP11 and exon
      11 of PDGFRB. However, the KIAA1509-PDGFRB fusion was not detected by RT-PCR.
      CONCLUSION: We firstly demonstrated that therapy-related myeloid neoplasm with
      TRIP11-PDGFRB fusion was identified after treatment of APL.

PMID- 25606058
TI  - Systematic evaluation of connectivity map for disease indications.
AB  - BACKGROUND: Connectivity map data and associated methodologies have become a
      valuable tool in understanding drug mechanism of action (MOA) and discovering new
      indications for drugs. One of the key ideas of connectivity map (CMAP) is to
      measure the connectivity between disease gene expression signatures and compound
      induced gene expression profiles. Despite multiple impressive anecdotal
      validations, only a few systematic evaluations have assessed the accuracy of this
      aspect of CMAP, and most of these utilize drug-to-drug matching to transfer
      indications across the two drugs. METHODS: To assess CMAP methodologies in a more
      direct setting, namely the power of classifying known drug-disease relationships,
      we evaluated three CMAP-based methods on their prediction performance against a
      curated dataset of 890 true drug-indication pairs. The disease signatures were
      generated using Gene Logic BioExpressTM system and the compound profiles were
      derived from the Connectivity Map database (CMAP, build 02,
      http://www.broadinstitute.org/CMAP/). RESULTS: The similarity scoring algorithm
      called eXtreme Sum (XSum) performs better than the standard Kolmogorov-Smirnov
      (KS) statistic in terms of the area under curve and can achieve a four-fold
      enrichment at 0.01 false positive rate level, with AUC = 2.2E-4, P value =
      0.0035. CONCLUSION: Connectivity map can significantly enrich true positive drug
      indication pairs given an effective matching algorithm.

PMID- 25606059
TI  - Comparison of DNA methylation profiles in human fetal and adult red blood cell
      progenitors.
AB  - BACKGROUND: DNA methylation is an epigenetic modification that plays an important
      role during mammalian development. Around birth in humans, the main site of red
      blood cell production moves from the fetal liver to the bone marrow. DNA
      methylation changes at the beta-globin locus and a switch from fetal to adult
      hemoglobin production characterize this transition. Understanding this globin
      switch may improve the treatment of patients with sickle cell disease and beta
      thalassemia, two of the most common Mendelian diseases in the world. The goal of
      our study was to describe and compare the genome-wide patterns of DNA methylation
      in fetal and adult human erythroblasts. METHODS: We used the Illumina
      HumanMethylation 450 k BeadChip to measure DNA methylation at 402,819 CpGs in ex
      vivo-differentiated erythroblasts from 12 fetal liver and 12 bone marrow CD34+
      donors. RESULTS: We identified 5,937 differentially methylated CpGs that overlap
      with erythroid enhancers and binding sites for erythropoiesis-related
      transcription factors. Combining this information with genome-wide association
      study results, we show that erythroid enhancers define particularly promising
      genomic regions to identify new genetic variants associated with fetal hemoglobin
      (HbF) levels in humans. Many differentially methylated CpGs are located near
      genes with unanticipated roles in red blood cell differentiation and
      proliferation. For some of these new candidate genes, we confirm the correlation
      between DNA methylation and gene expression levels in red blood cell progenitors.
      We also provide evidence that DNA methylation and genetic variation at the beta
      globin locus independently control globin gene expression in adult erythroblasts.
      CONCLUSIONS: Our DNA methylome maps confirm the widespread dynamic changes in DNA
      methylation that occur during human erythropoiesis. These changes tend to happen
      near erythroid enhancers, further highlighting their importance in erythroid
      regulation and HbF production. Finally, DNA methylation may act independently of
      the transcription factor BCL11A to repress fetal hemoglobin production. This
      provides cues on strategies to more efficiently re-activate HbF production in
      sickle cell disease and beta-thalassemia patients.

PMID- 25606060
TI  - Development of a monoclonal antibody specific to the endonuclease domain of the
      human LINE-1 ORF2 protein.
AB  - BACKGROUND: LINE-1 (L1) retrotransposons are common occupants of mammalian
      genomes representing about a fifth of the genetic content. Ongoing L1
      retrotransposition in the germ line and somatic tissues has contributed to
      structural genomic variations and disease-causing mutations in the human genome.
      L1 mobilization relies on the function of two, self-encoded proteins, ORF1 and
      ORF2. The ORF2 protein contains two characterized domains: endonuclease and
      reverse transcriptase. RESULTS: Using a bacterially purified endonuclease domain
      of the human L1 ORF2 protein, we have generated a monoclonal antibody specific to
      the human ORF2 protein. We determined that the epitope recognized by this
      monoclonal antibody includes amino acid 205, which is required for the function
      of the L1 ORF2 protein endonuclease. Using an in vitro L1 cleavage assay, we
      demonstrate that the monoclonal anti-ORF2 protein antibody partially inhibits L1
      endonuclease activity without having any effect on the in vitro activity of the
      human AP endonuclease. CONCLUSIONS: Overall, our data demonstrate that this anti
      ORF2 protein monoclonal antibody is a useful tool for human L1-related studies
      and that it provides a rationale for the development of antibody-based inhibitors
      of L1-induced damage.

PMID- 25606061
TI  - Repeated horizontal transfers of four DNA transposons in invertebrates and bats.
AB  - BACKGROUND: Horizontal transfer (HT) of transposable elements (TEs) into a new
      genome is considered as an important force to drive genome variation and
      biological innovation. However, most of the HT of DNA transposons previously
      described occurred between closely related species or insects. RESULTS: In this
      study, we carried out a detailed analysis of four DNA transposons, which were
      found in the first sequenced twisted-wing parasite, Mengenilla moldrzyki. Through
      the homology-based strategy, these transposons were also identified in other
      insects, freshwater planarian, hydrozoans, and bats. The phylogenetic
      distribution of these transposons was discontinuous, and they showed extremely
      high sequence identities (>87%) over their entire length in spite of their hosts
      diverging more than 300 million years ago (Mya). Additionally, phylogenies and
      comparisons of transposons versus orthologous gene identities demonstrated that
      these transposons have transferred into their hosts by independent HTs.
      CONCLUSIONS: Here, we provided the first documented example of HT of CACTA
      transposons, which have been so far extensively studied in plants. Our results
      demonstrated that bats had continuously acquired new DNA elements via HT. This
      implies that predation on a large quantity of insects might increase bat exposure
      to HT. In addition, parasite-host interaction might facilitate exchanging of
      their genetic materials.

PMID- 25606062
TI  - Activation of a bacterial mechanosensitive channel in mammalian cells by
      cytoskeletal stress.
AB  - Cells can sense a myriad of mechanical stimuli. Mechanosensitive channel of large
      conductance (MscL) found in bacteria is a well-characterized mechanosensitive
      channel that rapidly responds to an increase in turgor pressure. Functional
      expression of MscL in mammalian cells has recently been demonstrated, revealing
      that molecular delivery or transport can be achieved by charge-induced activation
      of MscL. Despite a well-accepted mechanism for MscL activation by membrane
      tension in bacteria, it is not clear whether and how MscL can be opened by other
      modes of force transduction in mammalian cells. In this work, we used a variety
      of techniques to characterize the gating of MscL expressed in mammalian cells,
      using both wild type and a G22S mutant which activates at a lower threshold. In
      particular, employing a new technique, acoustic tweezing cytometry (ATC), we show
      that ultrasound actuation of integrin-bound microbubbles can lead to MscL opening
      and that ATC induced MscL activation was dependent on the functional linkage of
      the microbubbles with an intact actin cytoskeleton. Our results indicate that
      localized mechanical stress can mediate opening of MscL that requires force
      transduction through the actin cytoskeleton, revealing a new mode of MscL
      activation that may prove to be a useful tool for mechanobiology and drug
      delivery research.

PMID- 25606064
TI  - PARP inhibitors.
AB  - Poly (ADP-ribose) polymerases, abbreviated as PARPs, are a group of familiar
      proteins that play a central role in DNA repair employing the base excision
      repair (BER) pathway. There about 17 proteins in this family out of which the
      primary nuclear PARPs are PARP-1, PARP-2, PARP-3, and tankyrases 1 and 2 (PARP-5a
      and -5b) .The PARP family members are known to engage in a wide range of cellular
      activities, for example, DNA repair, transcription, cellular signaling, cell
      cycle regulation and mitosis amongst others. The chief functional units of PARP-1
      are an amino terminal DNA binding domain (DBD), a central auto modification
      domain (AMD), and a carboxyl-terminal catalytic domain (CD). PARP inhibitors are
      currently undergoing clinical trials as targeted treatment modalities of breast,
      uterine, colorectal and ovarian cancer. This review summarizes current insights
      into the mechanism of action of PARP inhibitors, its recent clinical trials, and
      potential next steps in the evaluation of this promising class of anti-cancer
      drugs. 

PMID- 25606065
TI  - High-School Exit Examinations and the Schooling Decisions of Teenagers: Evidence
      From Regression-Discontinuity Approaches.
AB  - We examine whether barely failing one or more state-mandated high school exit
      examinations in Massachusetts affects the probability that students enroll in
      college. We extend the exit examination literature in two ways. First, we explore
      longer term effects of failing these tests. We find that barely failing an exit
      examination, for students on the margin of passing, reduces the probability of
      college attendance several years after the test. Second, we explore potential
      interactions that arise because students must pass exit examinations in both
      mathematics and English language arts in order to graduate from high school. We
      adopt a variety of regression-discontinuity approaches to address situations
      where multiple variables assign individuals to a range of treatments; some of
      these approaches enable us to examine whether the effect of barely failing one
      examination depends on student performance on the other. We document the range of
      causal effects estimated by each approach. We argue that each approach presents
      opportunities and limitations for making causal inferences in such situations and
      that the choice of approach should match the question of interest.

PMID- 25606063
TI  - Management of ovarian and endometrial cancers in women belonging to HNPCC carrier
      families: review of the literature and results of cancer risk assessment in
      Polish HNPCC families.
AB  - BACKGROUND: Over half the cancer deaths in HNPCC families are due to extra
      colonic malignancies that include endometrial and ovarian cancers. The benefits
      of surveillance for gynecological cancers are not yet proven and there is no
      consensus on the optimal surveillance recommendations for women with MMR
      mutations. METHODS: We performed a systematic review of the literature and
      evaluated gynecological cancer risk in a series of 631 Polish HNPCC families
      classified into either Lynch Syndrome (LS, MMR mutations detected) or HNPCC
      (fulfillment of the Amsterdam or modified Amsterdam criteria). RESULTS: Published
      data clearly indicates no benefit for ovarian cancer screening in contrast to
      risk reducing surgery. We confirmed a significantly increased risk of OC in
      Polish LS families (OR = 4,6, p < 0.001) and an especially high risk of OC was
      found for women under 50 years of age: OR = 32,6, p < 0.0001 (95% CI 12,96
      81,87). The cumulative OC risk to 50 year of life was calculated to be 10%. Six
      out of 19 (32%) early-onset patients from LS families died from OC within 2 years
      of diagnosis. We confirmed a significantly increased risk of EC (OR = 26, 95% CI
      11,36-58,8; p < 0,001). The cumulative risk for EC in Polish LS families was
      calculated to be 67%. CONCLUSIONS: Due to the increased risk of OC and absence of
      any benefit from gynecological screening reported in the literature it is
      recommended that prophylactic oophorectomy for female carriers of MMR mutations
      after 35 year of age should be considered as a risk reducing option. Annual
      transvaginal ultrasound supported by CA125 or HE4 marker testing should be
      performed after prophylactic surgery in these women. Due to the high risk of EC
      it is reasonable to offer, after the age of 35 years, annual clinical gynecologic
      examinations with transvaginal ultrasound supported by routine aspiration
      sampling of the endometrium for women from either LS or HNPCC families. An
      alternative option, which could be taken into consideration for women preferring
      surgical prevention, is risk reducing total hysterectomy (with bilateral salpingo
      oophorectomy) for carriers after childbearing is complete.

PMID- 25606066
TI  - [PREJUDICE AND SOCIAL DISTANCE TOWARD HOMOSEXUALS BY UNIVERSITY STUDENTS.]
AB  - We conduct a trans-sectional descriptive study to explore in 565 college
      students' prejudice attitude and social distance toward gay and lesbians (GL)
      people. We use a scale to measure prejudice and other scale to measure Social
      Distance. Participants show moderate levels of prejudice and social distance (SD)
      towards GLB people. Men's (M=104.5, DT= 27.47) shows significant more prejudice
      than woman's (M=98.8, DT= 23.41). Men's (M=22.7, DT= 7.00) shows more SD than
      women's (M=21.1, DT= 5.41). Those participants that attend regularly church
      services shows more prejudice and SD than those than not. The analysis of this
      findings strength the importance of incorporate sexual diversity issues in the
      curriculum to eradicate those prejudice to homosexual community.

PMID- 25606068
TI  - Editor's Note.

PMID- 25606067
TI  - Water Transport through Nanotubes with Varying Interaction Strength between Tube
      Wall and Water.
AB  - We present the results from extensive molecular dynamics simulations to study the
      effect of varying interaction strength, epsilonNT-OW, between the nanotube atoms
      and water's oxygen atom. We find the existence of a narrow transition region
      (epsilonNT-OW ~ 0.05 - 0.075 kcal/mol) in which water occupancy within a nanotube
      and flux through it increases dramatically with increasing epsilonNT-OW, with the
      exact location defined by nanotube diameter and length. This transition region
      narrows with increasing nanotube diameter to nearly a step-change in water
      transport from no flow to high water flux between epsilonNT-OW= 0.05 kcal/mol to
      0.055 kcal/mol for tube diameter 1.6 nm. Interestingly, this transition region
      (epsilonNT-OW= 0.05 - 0.075 kcal/mol) also coincides with water contact angles
      close to 90 degrees  on an unrolled nanotube surface hinting at a fundamental
      link between nanotube wetting characteristics and water transport through it.
      Finally, we find that the observed water flux is proportional to the average
      water occupancy divided by the average residence time within the nanotube, with a
      proportionality constant found to be 0.36, independent of the nanotube diameter
      and length.

PMID- 25606069
TI  - Evaluation and management of dyspepsia - current perspectives.

PMID- 25606071
TI  - Avoiding common errors in key feature problems.

PMID- 25606070
TI  - Summarizing research findings: systematic review and meta-analysis.
AB  - The explosion of biomedical publishing makes keeping up with the primary studies
      an impossible task. The often disparate, confusing and contradicting findings of
      individual studies makes healthcare professionals turn to review articles where
      knowledge has been collated and published in summaries. Narrative reviews lack
      rigorous, systematic and reproducible synthesis. In contrast, systematic reviews
      are conducted using systematic and explicit methods to identify, select and
      critically appraise relevant research, and to collect and analyse data from the
      studies that are included in the review. The final pathway for systematic review
      is a statistical summary of the results of primary studies, or meta-analysis.
      This article provides some guidelines to health care providers in understanding
      the key aspects of systematic review and meta-analysis. Steps involved in
      systematic review are discussed. The potential pitfall of meta-analysis was also
      explored. 

PMID- 25606072
TI  - Notes for the Primary Care Teachers: What do we Hope to Achieve in Family
      Practice Training and How: A brief look at the current trends in medical
      education.

PMID- 25606073
TI  - Notes for primary care: teachers how do adults learn?

PMID- 25606074
TI  - Notes for the primary care teachers: giving feedback.

PMID- 25606075
TI  - Notes for the primary care teachers: tips in preparing for a tutorial.

PMID- 25606076
TI  - Interpreting hepatitis B serology.

PMID- 25606077
TI  - An adult woman with Fever, cough and abnormal liver function.

PMID- 25606078
TI  - A 62 year old man with pain and stiffness of hands.

PMID- 25606079
TI  - Editor's Note.

PMID- 25606080
TI  - Current issues facing the introduction of human papillomavirus vaccine in
      malaysia.
AB  - Certain human papillomavirus (HPV) types are strongly associated with cervical
      cancer. Recently-described effective vaccines against these HPV types represent a
      great medical breakthrough in preventing cervical cancer. In Malaysia, the
      vaccine has just received regulatory approval. We are likely to face similar
      barriers to implementing HPV vaccination as reported by countries where
      vaccination has been introduced. Most women have poor understanding of HPV and
      its link to cervical cancer. Physicians who will be recommending HPV vaccines may
      not have extensive knowledge or experience with HPV-related disease. Furthermore,
      a vaccine against a sexually-transmitted infection may elicit negative reactions
      from potential recipients or their carers, particularly in a conservative
      society. Given the high cost of the vaccine, reaching the most vulnerable women
      is a concern. To foster broad acceptance of HPV vaccine, education must be
      provided to health care providers, parents and young women about the risks of HPV
      infection and the benefits of vaccination. 

PMID- 25606081
TI  - Urinary tract infections in pregnancy.
AB  - Urinary tract infections frequently affect pregnant mothers. This problem causes
      significant morbidity and healthcare expenditure. Three common clinical
      manifestations of UTIs in pregnancy are: asymptomatic bacteriuria, acute cystitis
      and acute pyelonephritis. Escherichia coli remains the most frequent organism
      isolated in UTIs. All pregnant mothers should be screened for UTIs in pregnancy
      and antibiotics should be commenced without delay. Urine culture and sensitivity
      is the gold standard in diagnosing UTIs. Without treatment, asymptomatic
      bacteriuria in pregnancy is associated with preterm delivery, intrauterine growth
      retardation, low birth weight, maternal hypertension, pre-eclampsia and anaemia.
      Acute pyelonephritis can lead to maternal sepsis. Recurrent UTIs in pregnancy
      require prophylactic antibiotic treatment. 

PMID- 25606082
TI  - The role of general practitioners in home oxygen therapy.
AB  - Recommendation of oxygen therapy must include clear indication and benefits of
      its use, appropriate prescription, vigilant monitoring and appropriate methods of
      delivery. Home oxygen therapy is expensive, inconvenient and cumbersome; it
      should be recommended only if benefits outweigh the disadvantages and adverse
      effects of oxygen. GPs play an important supportive and supervisory role in the
      use of long-term oxygen therapy (LTOT) to improve mortality of patients with
      chronic hypoxaemia. Prescription of short burst oxygen therapy (SBOT) for
      palliation of breathlessness is without clear evidence of its efficacy. GPs can
      prescribe SBOT when other secondary causes of breathlessness are excluded or
      treated, when breathlessness is not relieved by other treatments and if an
      improvement can be documented in patients. 

PMID- 25606085
TI  - Should Statins Be Started In All Type 2 Diabetics Irrespective of LDL-Cholesterol
      Level?

PMID- 25606083
TI  - Antimicrobial susceptibility of community-acquired uropathogens in general
      practice.
AB  - Antibiotic resistance of urinary tract pathogens has increased worldwide. The
      purpose of this study is to provide information regarding local resistance
      pattern of urinary pathogens to the commonly used antibiotics. One hundred and
      seventeen cases of community-acquired urinary tract infections were studied. The
      most common group of patients was the uncomplicated acute cystitis in women. E.
      coli was the most common isolate. Overall, antimicrobial susceptibility test on
      the organisms isolated showed a resistance of 63.0% to ampicillin, 40.1% to
      sulfamethoxazole-trimethoprim (S-T), 14.3% to pipemidic acid, 8.6% to
      norfloxacin, 3.8% to cephalexin, 3.7% to amoxicillin-clavulanate, 1.0% to
      cefuroxime, and 1.0% to fosfomycin. Three out of five patients on ampicillin as
      well as two out of five patients on S-T were likely to be inadequately treated. 

PMID- 25606084
TI  - Recurrent stroke: what have we learnt?
AB  - Stroke is the third leading cause of death, a major cause of disability in
      adults, and is frequently more disabling than fatal. With a decline in mortality
      from initial cerebral infarction and an increase in the life expectancy of the
      population, the number of patients with recurrent stroke and ensuing
      cardiovascular events will become greater. Thus it is important to find out those
      patients at high risk of stroke recurrence. This case report illustrates the
      process of recurrent stroke and the resulting disabilities and morbidities in a
      42-year- old man. The role of integrated stroke rehabilitation programme is
      described. 

PMID- 25606086
TI  - Notes for primary care teachers: mentoring - a personal experience.

PMID- 25606087
TI  - Notes for primary care teachers: assessments - the basics.

PMID- 25606088
TI  - Notes for Primary Care Teachers: Assessments - the Conjoint MAFP/FRACGP
      Examination.

PMID- 25606089
TI  - A young man with chronic cough.

PMID- 25606090
TI  - A middle-aged man with pain and swelling of the hands.

PMID- 25606092
TI  - Editor'S note.

PMID- 25606091
TI  - A toddler with limping.

PMID- 25606093
TI  - Depression in primary care, part 1: screening and diagnosis.
AB  - One of the commonest psychological problems that a clinician would encounter in
      primary care is depression. The prevalence of depression is high in women, the
      elderly and those with underlying physical problems or during the postpartum
      period. The spectrum of clinical presentations is wide and somatic complaints are
      more common in primary care clinics. Depression may present as a primary disorder
      and co-morbidity with other psychological problems or physical illnesses is high.
      A good clinical interview is an important form of assessment and a quick
      screening of depression can be done with the administration of proper rating
      scales, such as the Patient Health Questionnaire, Hamilton Depression Rating
      Scale or Geriatric Depression Scale. Repeated use of the same scale in a patient
      would help the clinician to monitor the progress objectively. 

PMID- 25606094
TI  - Depression in primary care part 2: management.
AB  - The management of depression in the primary care setting should ideally take a
      biological, psychological, and sociological approach. Antidepressants are the
      most commonly used biological agents in the treatment of depression.
      Psychological therapies and psychosocial interventions improve the outcome of
      treatment when combined with pharmacotherapy. Clinical depression is treatable
      and thus efforts should be made to alleviate the suffering of patients with
      depression. 

PMID- 25606095
TI  - Imaging as an aid to the diagnosis of acute appendicitis.
AB  - Acute appendicitis has been known as a disease entity for well over a century but
      a confident diagnosis before surgery in all patients suspected of the condition
      is still not possible. Timely diagnosis is essential to minimise morbidity due to
      possible perforation of the inflamed organ in the event treatment is delayed; so
      much so that surgeons often preferred to operate at the slightest suspicion of
      the diagnosis in the past. This resulted in the removal of many normal
      appendixes. When the diagnosis of appendicitis is clear from the history and
      clinical examination, then no further investigation is necessary and prompt
      surgical treatment is appropriate. Where there is doubt about the diagnosis
      however it is advisable to resort to imaging studies such as abdominal ultrasound
      or computed tomography to clear such suspicions before subjecting the patient to
      an appendicectomy. These studies would also help avoid delays in surgery in
      deserving patients. 

PMID- 25606097
TI  - Notes for the Primary Care Teachers: TIPS FOR THE NEW MEDICAL TEACHER.

PMID- 25606096
TI  - A patient who refused medical advice: the doctor and the patient should look for
      a common ground.
AB  - Treatment refusal is a common encounter in clinical practice. The process of
      deciding to refuse treatment is often complex. It is our responsibility to try
      and understand this process of decision making and the underlying reasons for
      treatment refusal. Many of these reasons are often rational in the context where
      the decision is made. The patients could be making the best decision for
      themselves even if these decisions are not necessarily the best in our mind. We
      should at all times discuss our treatment options and assess their ability to
      make decisions in achieving common goals. These goals should balance our best
      treatment strategies and the patients' best interest. This article discusses the
      reasons underlying treatment refusal and how we can achieve a common goal with
      our patients. 

PMID- 25606098
TI  - Notes for the Primary Care Teachers: TEACHING DOCTOR-PATIENT COMMUNICATION IN
      FAMILY MEDICINE.
AB  - Doctor-patient communication skills are important in family medicine and can be
      taught and learned. This paper summarises the salient contents and main methods
      of the teaching and learning of doctor-patient communication, especially those
      applicable to the discipline. 

PMID- 25606099
TI  - Notes for the Primary Care Teachers: THE EFFECTIVE TEACHER.

PMID- 25606100
TI  - Notes for the Primary Care Teachers: PORTFOLIO ASSESSMENT.
AB  - The portfolio consists of a variety of documentation of a learner's proof of
      learning. It has been promoted as one way to verify a learner's personal and
      professional development, especially for the more mature trainees and doctors at
      work. It has not been widely accepted as a summative tool because the amount of
      time imposed on the learners may be considerable. Ways to improve the reliability
      of assessments on unstandardised portfolios are needed for its wider application.

PMID- 25606101
TI  - A young man with loin pain.

PMID- 25606102
TI  - A 55 year-old man with lethargy for six months.

PMID- 25606103
TI  - Editor's Note.

PMID- 25606104
TI  - Understanding patient management: the need for medication adherence and
      persistence.
AB  - Poor patient adherence to medication is one of the major factors contributing to
      poor disease control, in particular in asymptomatic chronic diseases like
      hypertension and dyslipidaemia. The physical and economic burden on patients and
      the health care system as a result of non-adherence is great. It is estimated
      that poor adherence to hypertension medication accounts for as many as 7.1
      million preventable deaths annually. Hence recognising and identifying non
      adherence is the first step to addressing this problem. Medication adherence can
      be measured in various ways including self-report to electronic monitoring. In
      order to be more successful in managing non-adherence, attention must be paid to
      barriers to adherence, namely the interplay of patient factors, the health care
      providers themselves and the health care system itself. Taking these into account
      will probably have the greatest impact on improving medication adherence.
      Consequently strategies to help overcome these barriers are of paramount
      importance. Some of these strategies will include education of patients,
      improving communication between patients and health care providers, improving
      dose scheduling, providing drugs with less adverse effects, and improving
      accessibility to health care. Poor mediation adherence continues to be a huge
      challenge. While the patient is ultimately responsible for the taking of
      medication, good communication, involving the patient in decision making about
      their care and simplifying drug regimens go a long way in improving it. 

PMID- 25606105
TI  - Managing chronic diseases in the malaysian primary health care - a need for
      change.
AB  - Chronic diseases are the major cause of death and disability in Malaysia,
      accounted for 71% of all deaths and 69% of the total burden of disease. The WHO
      in its report Preventing Chronic Disease: A Vital Investment has highlighted the
      inaction of most governments of the low and middle income countries in tackling
      the problem urgently, is clear and unacceptable. The acute care paradigm is no
      longer adequate for the changing pattern of diseases in today's and tomorrow's
      world. An evolution of primary health care system beyond the acute care model to
      embrace the concept of caring for long term health problems is imperative in the
      wake of the rising epidemic of chronic diseases and its crushing burden resulting
      in escalating healthcare costs. Compelling evidence from around the world showed
      that there are innovative and cost-effective community-based interventions to
      reduce the morbidity and mortality attributable to chronic diseases, but these
      are rarely translated into high quality population-wide chronic disease care.
      This paper describes the current situation of chronic disease management in the
      Malaysian primary care setting - to highlight the need for change, discuss the
      barriers to the implementation of effective chronic disease management programmes
      in the community, and consider fundamental solutions needed to instigate the
      change in our setting. 

PMID- 25606106
TI  - Data analysis in qualitative research: a brief guide to using nvivo.
AB  - Qualitative data is often subjective, rich, and consists of in-depth information
      normally presented in the form of words. Analysing qualitative data entails
      reading a large amount of transcripts looking for similarities or differences,
      and subsequently finding themes and developing categories. Traditionally,
      researchers 'cut and paste' and use coloured pens to categorise data. Recently,
      the use of software specifically designed for qualitative data management greatly
      reduces technical sophistication and eases the laborious task, thus making the
      process relatively easier. A number of computer software packages has been
      developed to mechanise this 'coding' process as well as to search and retrieve
      data. This paper illustrates the ways in which NVivo can be used in the
      qualitative data analysis process. The basic features and primary tools of NVivo
      which assist qualitative researchers in managing and analysing their data are
      described. 

PMID- 25606107
TI  - Exercise-induced asthma: fresh insights and an overview.
AB  - Exercise-induced asthma (EIA) is a common condition affecting 12-15% of the
      population. Ninety percent of asthmatic individuals and 35-45% of patients with
      allergic rhinitis are afflicted by EIA, while 3-10% of the general population is
      also believed to suffer from this condition. EIA is a condition which is more
      prevalent in strenuous outdoor, cold weather and winter sports. The
      pathophysiology of EIA continues to intrigue medical physiologists. However, the
      water-loss hypothesis and the post-exertional airway-rewarming hypothesis are as
      yet the best accepted theories. EIA is best diagnosed by a good medical history
      and a free-run challenge test. A post-exertion decrease by 15% in FEV1 and PEFR
      is diagnostic of EIA. Sensitivity of exercise testing ranges from 55% to 80%
      while specificity is as high as 93%. EIA is a disorder that can be successfully
      treated by combining both non-pharmacological and pharmacological treatment
      options. Prompt diagnosis and treatment of this condition is vital if we hope to
      provide our patients with better overall health, better social life and a better
      self-image. 

PMID- 25606108
TI  - Prevalence of eye diseases and visual impairment in urban population - a study
      from university of malaya medical centre.
AB  - One thousand one hundred and sixty-nine (1169) patients were examined in the Eye
      Clinic of University of Malaya Medical Centre over a period of three weeks to
      determine the prevalence of eye diseases and visual impairment. Age, gender,
      race, visual acuity and diagnosis of patients were noted from the case records.
      Cataract (385, 32.9%) was the most common eye disease seen in our study followed
      by glaucoma (274, 23.4%). Refractive errors were seen in 126 (10.8%) while
      diabetic retinopathy was noted in 113 (9.7%) patients. One hundred and fifteen
      (9.6%) patients had visual impairment and 11 (0.9%) had blindness in our study
      according to WHO classification of visual impairment. Refractive errors are the
      most common causes of visual impairment in children, while cataract, glaucoma and
      diabetic retinopathy account for visual impairment in elderly people. All these
      eye diseases are treatable and the severe eye conditions may be potentially
      preventable with early diagnosis. 

PMID- 25606109
TI  - Should Beta Blockers Still be Recommended as First-Line Therapy for Essential
      Hypertension in Younger Patients?

PMID- 25606110
TI  - Two Adults With Hypertriglyceridemia: How should one manage these persons?(#).
AB  - The paper discusses the management of two individuals with asymptomatic
      hypertriglyceredemia, a common problem faces by Family Physicians in Malaysia. In
      such instances it is advisable to exclude an underlying disorder (e.g. metabolic
      syndrome) and take a pragmatic approach. 

PMID- 25606111
TI  - Notes for primary care teachers: teaching methods used in primary care.

PMID- 25606112
TI  - Notes for Primary Care Teachers: Self-Directed Learning: What it is, and How to
      Promote it.

PMID- 25606113
TI  - A man with febrile illness and difficulty in walking.

PMID- 25606114
TI  - Leadership in the ministry of health.
AB  - Leadership in a huge and complex organisation like the Ministry of Health is
      important. The importance of leadership lies in the role it plays in defining the
      character, values and direction of an organization; and it's relation to
      organizational performance. Leadership is a quality that must be embedded within
      an organization for the organization to be successful and meet its objectives.
      Good leaders can be developed through a continuous process of self-study,
      education, training and experience. This concept of leadership also highlights
      the importance of seeking people with leadership talent, developing their
      potential and providing opportunities for them to lead. 

PMID- 25606115
TI  - Training in male sexual and reproductive health for a primary care physician.
AB  - In 2006, I was awarded a scholarship from Universiti Sains Malaysia for
      Fellowship training at Monash University (MU) for one year. The objective of the
      training programme was to develop knowledge and skills in several areas,
      including androgen deficiency, male infertility, prostate disease, testicular
      tumours, sexual dysfunction and sexually transmitted diseases. The training
      programme consisted of attachments with clinical specialists, completion of a
      course work module and a research project. After completion of the training
      programme, I believe that Primary Care Physicians (PCPs) will benefit from
      undertaking the training programme that I had completed. It will enable PCPs to
      assume leadership roles in this multidisciplinary area. The ability of PCPs in
      handling sexual and reproductive health issues in men will definitely be a more
      cost effective form of care for patients, particularly as the number of
      specialists is limited, and even more importantly, it will be satisfying for the
      patient and the physician. 

PMID- 25606116
TI  - Training program in the field of addiction medicine - an experience of learning
      while abroad.
AB  - This paper illustrates the training program in the field of Addiction Medicine
      designed for primary care doctors by the Department of General Practice, School
      of Primary Care at Monash University in Melbourne. The nine month program was
      based around coursework, field visits and clinical observations. There were five
      modules that were completed and passed, twenty six Continuous Medical Education
      sessions attended, twenty nine field visits on Drug & Alcohol services, forty
      seven clinical visits and a total of three hundred and sixty clinical
      observations made. The comprehensive training program has benefited the first
      author in several ways to improve the Drugs & Alcohol services in Malaysia. 

PMID- 25606117
TI  - Family physicians with special interest in dermatology.

PMID- 25606119
TI  - Editor's Note.

PMID- 25606118
TI  - Qualitative research methods in family medicine: what and why?

PMID- 25606120
TI  - Prehypertension: What is the Current Status?
AB  - Cardiovascular disease (CVD) risk is a continuum across blood pressure. The term
      prehypertension was introduced because it is now recognized that blood pressure
      readings between what is deemed optimal and hypertension is associated with
      increased CVD risk. The prevalence of prehypertension is high and the progression
      to hypertension is also high. Prehypertension is also commonly associated with
      other CVD risk factors namely dyslipidaemia, dysgylcaemia and overweight/
      obesity. Eighty-five percent of prehypertensives have one other or more CVD risk
      factor compared to normotensives. A recent study has shown a reduction in the
      development of hypertension from prehypertension with the use of an angiotensin
      receptor blocker. Unfortunately to date, the impact of treatment of
      prehypertension on CVD outcome is still unknown except in those with high CVD
      risk like diabetes or established CVD. However this does not mean nothing can be
      done for those with prehypertension. The aim of managing prehypertension is to
      lower the BP, prevent progression to hypertension and to prevent BP related CVD
      deaths. Lifestyle changes can reduce BP and this by itself can lower CVD risk.
      Until more evidence about other modalities of treatment become available this is
      a sensible and cost-effective way to manage prehypertension. 

PMID- 25606121
TI  - Neonatal conjunctivitis - a review.
AB  - Ophthalmia neonatorum remains a significant cause of ocular morbidity, blindness
      and even death in underdeveloped countries. The organisms causing ophthalmia
      neonatorum are acquired mainly from the mother's birth canal during delivery and
      a small percentage of cases are acquired by other ways. Chlamydia and Neisseria
      are the most common pathogens responsible for the perinatal infection.
      Fortunately in most cases, laboratory studies can identify the causative organism
      and unlike other form of conjunctivitis, this perinatal ocular infection has to
      be treated with systemic antibiotics to prevent systemic colonization of the
      organism. Routine prophylaxis with 1% silver nitrate solution (credes method) has
      been discontinued in many developed nations for the fear of development of
      chemical conjunctivitis. 

PMID- 25606122
TI  - A comparison of headache and non-headache sufferers on measures of social support
      and mental health problems.
AB  - 138 headaches sufferers and 138 subjects without headaches were studied to
      investigate if there were differences between headache and non-headache sufferers
      in terms of their mental health and social support levels. The overall results of
      this study indicated that headache sufferers, as compared with non-headache
      sufferers had slightly more mental health problems, and more social support from
      their family members. When the results were scrutinised in more detail, it was
      observed that headache sufferers reported that they felt less capable of making
      decisions about things, were not always able to face up to their problems, and
      sometimes thought about themselves as a worthless. Given that the study was based
      on a community, rather than clinic sample, further research would be required to
      examine the differing the types of headaches that people are suffering from, and
      the intensity of the headaches, in relation to mental health problems. 

PMID- 25606123
TI  - Ethambutol ocular toxicity in a patient with pulmonary tuberculosis - a case
      report.
AB  - Purpose. To highlight the importance of using the Farnsworth Panel D-15 Hue test
      in colour vision testing in patients on ethambutol treatment. Case Report. A 70
      year-old lady received ethambutol as part of her anti-tuberculous regime. She
      developed blue-yellow colour defect detectable with the Farnsworth Panel D-15 Hue
      test, but not with the Isihara Pseudoisochromatic Plates. Ethambutol was
      immediately discontinued from her anti-tuberculous regime. Two months later, her
      colour vision returned to normal. Conclusion. This case report illustrates the
      importance of regular monitoring of patients receiving ethambutol for blue-yellow
      colour defect using the Farnsworth Panel D-15 Hue Test. 

PMID- 25606124
TI  - Is the Combination of Aspirin and Clopidogrel always Better than Aspirin Alone?
      Or will it be too much of a good thing?

PMID- 25606125
TI  - Is HIV Screening in the General Population Cost Effective?

PMID- 25606126
TI  - Are inhaled long-acting Beta-agonists (laba) really harmful in adult asthmatics?

PMID- 25606127
TI  - Notes for the primary care teacher: teaching in the family practice clinics.

PMID- 25606128
TI  - Notes for the primary care teacher: quality assurance in teaching.

PMID- 25606129
TI  - A woman presenting with dry cough, hoarseness of voice and significant weight
      loss.

PMID- 25606130
TI  - A baby with an abnormal upper limb.

PMID- 25606131
TI  - A man with an acute abdomen.

PMID- 25606132
TI  - National malaysian twin registry - a perfect opportunity for researchers to study
      nature versus nurture.

PMID- 25606133
TI  - The arthritis and musculoskeletal quality improvement program (amquip): a
      breakthrough series methodology project.
AB  - The Australian government had funded the National Primary Care Collaborative
      (NPCC) program with funding of $14.6 million over three years. One of the pilots
      project was the Arthritis and Musculoskeletal Quality Improvement Program
      (AMQuIP).The study aims to optimize general practitioners (GPs) management of
      patients with osteoarthritis (OA) of the hip and knee by identifying gaps between
      their current practice and best practice. The Breakthrough Series Collaborative
      methodology with several Plan-Do-Study-Act (PDSA) cycles was employed.
      Participants comprises of 12 GPs/practices from two Victorian Divisions of
      general Practice (one rural, one metropolitan) with 10 patients per GP/practice.
      GPs/practices attended an orientation and three learning workshops and a
      videoconference. GPs/practices completed PDSA cycles between workshop and
      reported results at workshops. GPs/practices reported use of guidelines, change
      in patient management and change in practice management/systems. All recruited
      patients completed the SF-12v2 Health Survey and WOMAC OA Index Questionnaire
      twice. Follow up activities including focus groups and face-to-face interviews
      were held six months after the final workshop. All GPs/practices used the
      guidelines/key messages, introduced "new" management strategies to patients, and
      made positive changes to their practice management/systems. Patient reported
      positive changes and outcomes. By using a structured methodology and evidence
      based guidelines/key messages; GPs can introduce new patient management
      strategies, and by identifying gaps in practice management systems, positive
      changes can be achieved. 

PMID- 25606135
TI  - Editor's Note.

PMID- 25606134
TI  - Know the Medicinal Herb: Catharanthus roseus (Vinca rosea).

PMID- 25606136
TI  - Understanding and preventing computer vision syndrome.
AB  - The invention of computer and advancement in information technology has
      revolutionized and benefited the society but at the same time has caused symptoms
      related to its usage such as ocular sprain, irritation, redness, dryness, blurred
      vision and double vision. This cluster of symptoms is known as computer vision
      syndrome which is characterized by the visual symptoms which result from
      interaction with computer display or its environment. Three major mechanisms that
      lead to computer vision syndrome are extraocular mechanism, accommodative
      mechanism and ocular surface mechanism. The visual effects of the computer such
      as brightness, resolution, glare and quality all are known factors that
      contribute to computer vision syndrome. Prevention is the most important strategy
      in managing computer vision syndrome. Modification in the ergonomics of the
      working environment, patient education and proper eye care are crucial in
      managing computer vision syndrome. 

PMID- 25606137
TI  - Classifying asthma severity and treatment determinants: national guidelines
      revisited.
AB  - Bronchial asthma is an inflammatory disease of the airways manifested
      physiologically by a widespread narrowing of the air passages. Being an
      inflammatory disease of the airways, the most effective treatment available for
      the management of bronchial asthma are anti-inflammatory agents such as
      corticosteroids. However, it is known that at higher dosage levels, even inhaled
      corticosteroids have harmful systemic side-effects. Hence, justification of use
      of high-dose of inhaled corticosteroids can only be made if patients with severe
      asthma can be accurately identified. For this precise reason, methods have been
      devised to categorize asthma severity through various National Asthma Management
      Guidelines. The present guidelines predominantly stress on symptoms and lung
      functions as the yardstick for determining the severity of asthma attacks and
      parameters determining airway inflammation have not yet been incorporated into
      them. However, these guidelines have proved to be fairly accurate in determining
      asthma severity and in guiding the treatment in these patients and all healthcare
      personnel are strongly advised to follow them. It is hoped that future guidelines
      may incorporate measures of inflammation as well, in order to further improve the
      diagnostic and treatment modalities in these patients. 

PMID- 25606138
TI  - An Older Woman in Early Pregnancy: What Antenatal Screening is Appropriate?

PMID- 25606139
TI  - Pattern of ocular trauma in kuching, malaysia.
AB  - OBJECTIVES: To analyze the causes and characteristics of ocular injuries
      presenting to Sarawak General Hospital (SGH), Kuching. DESIGN: It is a
      prospective hospital-based study done for a period of 1 year. SETTING: Department
      of Ophthalmology, Sarawak General Hospital, Malaysia. PARTICIPANTS: All ocular
      injury patients seen for the first time in the Eye Department during the period
      January 2006 to December 2006 were included in the study. Eye injury patients on
      follow-up and treated elsewhere were excluded. RESULTS: A total of 233 patients,
      and 257 eyes, were studied. Men had six-fold higher rates of injury than women.
      The average age of presentation was 30 years. The predominant age group was
      between 21-30 years, 26.2 % (n=61). Eye injuries related to work were seen in
      36.9% of patients. There was a gross negligence in the use of personal protective
      devices in the work-related group. The common settings in which the injuries
      occurred included home 34.3% (n=80) and industrial premises 31.8% (n=74). Assault
      related injuries 7.7% (n=18) were seen mostly among young men in the age between
      20-30 years. The initial presenting visual acuity of the patients with blunt
      ocular trauma was better than penetrating injury. CONCLUSION: Ocular injuries
      were common in young males. Work related eye injuries were noted in a significant
      number of cases. Health education and preventive strategies both in the working
      place and at home will help to decrease the occurrence of ocular injuries.

PMID- 25606141
TI  - Role of exercise in patients with symptomatic knee osteoarthritis.

PMID- 25606140
TI  - A mentally retarded patient with schizophrenia.
AB  - Schizophrenia is one of the most incapacitating forms of mental disorder that
      runs a chronic and relapsing course. It typically starts in adolescence or early
      adulthood and can be life-long. It is more common in people with learning
      disabilities than in the general population. Its prodromal features include
      depression, anxiety, suspiciousness, social isolation and bizarre behaviour. It
      may result in significant functional, social and economic impairments. The care
      of patients with schizophrenia places a considerable burden on all carers
      including patient's family, health and social services. Treatment includes
      pharmacotherapy and psychosocial interventions. In this case report we describe a
      thirteen-year-old patient with schizophrenia who has a background history of
      mental retardation. 

PMID- 25606142
TI  - Frequent Ventricular Ectopics in a Healthy Adult Woman - is it Associated with
      Sudden Cardiac Death?

PMID- 25606143
TI  - White coat effect and white coat hypertension: one and the same?
AB  - White coat hypertension (WCHT) and white coat effect (WCE) are often thought to
      be of the same entity. They are in fact different conditions which carry
      distinctive definitions and prognostic significance. WCHT is diagnosed when
      office blood pressure (OBP) is >=140/90 mmHg on at least 3 occasions, while the
      average daytime or 24-hour blood pressure is <135/85 mmHg. It is common with 15%
      prevalence in the general population and may account for over 30% of individuals
      in whom hypertension is diagnosed. Although individuals with WCHT were reported
      to have a better cardiovascular (CV) prognosis when compared to those with
      sustained hypertension and masked hypertension; they were also shown to have a
      greater prevalence of target organ damage (TOD) and metabolic abnormalities than
      that of normotensive subjects. In contrast, WCE is defined as the transient
      elevation of OBP induced by the alerting response to a doctor or a nurse. WCE can
      occur in both normotensive and hypertensive persons; and is not substantially
      influenced by reassurance and familiarisation. There is conflicting evidence with
      regards to prognostic significance of WCE, where most data indicated that it does
      not predict future TOD, CV morbidity or mortality; with some studies showed
      otherwise. This case scenario aims to solve the diagnostic perplexity with
      regards to WCHT and WCE, followed by an evidence-based commentary of how to best
      manage such conditions. 

PMID- 25606144
TI  - A boy with prolonged Fever.

PMID- 25606145
TI  - A man with claw hand.

PMID- 25606146
TI  - A woman with pain and stiffness of hands.

PMID- 25606147
TI  - Respiratory clinics ventilatory management in a patient with chronic obstructive
      pulmonary disease: a need for caution.

PMID- 25606148
TI  - Reflecting on Research: Self- Monitoring of Blood Glucose among Diabetes Patients
      Attending Government Health Clinics.
AB  - This article described the author's reflection on conducting research in primary
      care. Certainly hand-on experience will give a better learning experience for a
      person to explore further in research and research training will help too.
      Conducting a collaborative research with other institutions also help in better
      research outcome. Research capacity building is important as most patients are
      seen in primary care. 

PMID- 25606150
TI  - Editor's Note.

PMID- 25606149
TI  - Know the Common Substance: Table Salt (Sodium chloride, NaCl).

PMID- 25606151
TI  - Thyroid associated ophthalmopathy - a review.
AB  - Thyroid associated ophthalmopathy is an autoimmune disorder affecting the orbital
      and periorbital tissues. Hyperthyroidism is commonly associated with thyroid
      associated ophthalmopathy, however in 5% to 10% of cases it is euthyroid.
      Genetic, environmental and endogenous factors play a role in the initiation of
      the thyroid ophthalmopathy. Smoking has been identified as the strongest risk
      factor for the development of the disorder. The pathogenesis involves activation
      of both humoral and cell mediated immunity with subsequent production of
      gycoaminoglycans, hyaluronic acid resulting in oedema formation, increase
      extraocular mass and adipogenesis in the orbit. The natural history of the
      disease progresses from active to inactive fibrotic stage over a period of years.
      Diagnosis is mainly clinical and almost all patients with ophthalmopathy exhibit
      some form of thyroid abnormality on further testing. Treatment is based on the
      clinical severity of the disease. Non-severe cases are managed by supportive
      measures to reduce the symptomatology and severe cases are treated by either
      medical or surgical decompression. Rehabilitative surgery is done for quiescent
      disease to reduce diplopia and improve cosmesis. 

PMID- 25606152
TI  - Street ketamine-associated bladder dysfunction: an emerging health problem.
AB  - INTRODUCTION: Ketamine is frequently abused nowadays as a recreational drug. Case
      reports are emerging since 2007 to describe a new clinical entity of severe
      bladder dysfunction associated with chronic abuse of street ketamine. CLINICAL
      PRESENTATION: Severe lower urinary tract symptoms of urinary frequency and
      urgency which are refractory to conventional treatment. Quality of life is
      adversely affected as a consequence. Chronic kidney disease will develop in
      advanced cases. Investigation findings: The urine is sterile on culture.
      Ultrasound will show reduced bladder capacity with thickened bladder wall. In
      advanced stage, hydronephrosis and renal impairment will develop. TREATMENT:
      Patients should be advised to stop street ketamine use immediately.
      Anticholinergic medication could be tried to alleviate the symptoms. Refractory
      cases with dilatation of the upper urinary tract might need urinary diversion.
      CONCLUSION: Awareness of this new condition is essential in diagnosis. Early
      intervention offers better treatment outcome.

PMID- 25606153
TI  - Evidence based medicine series: evidence based medicine: an overview.

PMID- 25606154
TI  - Evidence based medicine series: asking focused answerable clinical questions.

PMID- 25606155
TI  - The Importance of Ophthalmic Signs in the Diagnosis of Suprasellar Meningioma - a
      case report.
AB  - A forty-two year old lady presented with gradual, painless, progressive blurring
      of vision of her left eye for four months. There were no other associated ocular
      or systemic complaints. Examination showed decreased visual acuity in both eyes
      and a pale optic disc on the left side. Visual field examination revealed a
      temporal field defect of the right eye which aroused the suspicion of an
      intracranial mass lesion. MRI of her brain revealed a suprasellar meningioma. We
      would like to emphasize the importance of visual field examination of both eyes
      in patients presenting with unilateral loss of vision. 

PMID- 25606156
TI  - Infantile blount disease: a case report.
AB  - Blount disease is an acquired growth disorder of the medial aspect of the
      proximal tibial physis, epiphysis and metaphysis. Infantile Blount disease
      present with bowing and length discrepancy in the lower limbs. The deformed
      medial tibial metaphysis represent as nontender bony protuberance can be palpated
      along the medial aspect of the proximal tibia. Here, we present an 18-month-old
      boy presented with the complaints of bilateral bowing of lower limb with normal
      biochemical investigation and radiological survey revealed Blount disease. 

PMID- 25606157
TI  - Missing an osteoporotic vertebral fracture.
AB  - This case illustrates an 80-year-old lady who presented with acute low back pain
      and finally succumbed from complications of osteoporotic vertebral fracture.
      Among the contributing factors are delayed diagnosis and a lack of continuity of
      care. It reminds the practitioners of the importance to look out for red flag
      symptoms and to have a high index of suspicion for vertebral fracture in high
      risk patients presenting with low back pain. 

PMID- 25606158
TI  - Exercise-Induced Rhabdomyolysis with Acute Renal Failure After Strenuous Push
      UPS.

PMID- 25606159
TI  - A woman with Fever and neck pain.

PMID- 25606161
TI  - Editor's Note.

PMID- 25606160
TI  - Respiratory clinics: left-sided hydropneumothorax in a young male: importance of
      clinical and radiological markers in arriving at an aetiological diagnosis.

PMID- 25606162
TI  - Common laboratory tests for rheumatological disorders: how do they help the
      diagnosis?
AB  - No screening test is ideal for detecting rheumatic diseases; diagnosis depends on
      appropriate history and thorough physical examination. Sometimes, laboratory
      investigations may be useful in confirming or ruling out rheumatic disease after
      a clinical diagnosis is considered. Once a rheumatic disease has been diagnosed,
      certain laboratory tests can help in assessing prognosis or determining the
      extent of the disease. Laboratory tests may also help the physician monitor
      certain rheumatic diseases, guide treatment or assess potential drug toxicity. 

PMID- 25606163
TI  - Masquerades of cluster headache.
AB  - Many cluster headache (CH) patients waited several years to be accurately
      diagnosed because their symptoms are often mistaken for sinusitis or a dental
      disorder.1 Patients have also been mistakenly diagnosed as analgesic drug abusers
      or suffering from a psychiatric illness. This case report illustrates how a young
      lady was diagnosed to have cluster headache after several years of consultations
      with ophthalmologists for eye swelling and redness. It also highlights the
      importance of pain assessment and a general and holistic approach to medical care
      which is the main distinguishing feature of Family Medicine. 

PMID- 25606164
TI  - Evidence Based Medicine Series: Part 3. Appraising the Evidence are the results
      valid and clinically Important?

PMID- 25606165
TI  - Evidence Based Medicine Series: Part 4. Why Some Good Studies with Clinically
      Important Results Cannot be Applied to Our Patients.

PMID- 25606166
TI  - Is it Necessary to Excise All Breast Lesions? Experience from a University-Based
      Breast Unit.
AB  - BACKGROUND: Breast cancer is becoming more important in Asia since it affect the
      younger age group. Question arises whether it is safe for breast lesions to be
      left in-situ if all the elements in triple assessment are benign. The aim of this
      study is to audit all the excision biopsies of breast lumps done in the
      University Malaya Medical Centre (UMMC), to review the association of age with
      the type of pathological finding and to evaluate the rate of carcinoma in these
      biopsies. METHODS: We conducted a retrospective study of all women who had
      excision biopsy of a breast lump in the University Malaya Medical Centre from
      January 2005 to December 2006. All patients with malignant preoperative biopsies
      were excluded. RESULTS: Of 717 lesions in 664 patients, 459 (64%) were
      fibroadenoma, 114 (15.9%) were fibrocystic disease, 20 (2.8%) were phylloides
      tumour, 27 (3.8%) were papilloma, 59 (8.2%) were malignant and 38 (5.3%) were of
      other pathology. Of the 717 open biopsies, 449 (62.6%) had fine-needle aspiration
      cytology (FNAC), 31 (4.3%) had core needle biopsy (CNB), while 14 (2.0%) had both
      FNAC and CNB done prior to excision biopsy. 251 (35%) had neither FNAC nor CNB.
      The incidence of fibroadenoma decreased with increasing age and the incidence of
      fibrocystic changes and papilloma increased with increasing age. There was no
      association of age with phylloides tumour. The incidence of unexpected malignancy
      increased with increasing age. The incidence rates were 0.3%, 4.5%, 19.4%, 29.7%
      and 29.6% for the age group below 30, 30-39, 40-49, 50-59 and above 60 years of
      age respectively. Of the 59 malignant lesions, FNAC was performed on 47 (79.7%)
      and CNB on 16 (27.1%). 9 had both FNAC and CNB and 3 had neither FNAC nor CNB.
      Out of the 56 lesions where FNAC/CNB were done, 23 (41.1%) were reported as
      benign, 20 (35.7%) as suspicious, 4 (7.1%) as atypical, 5 (8.9%) as inadequate, 2
      (3.6%) as equivocal and 2 (3.6%) as lymphoid lesions. Out of the 23 prior
      biopsies reported as benign, 22 were in the age group above 40. CONCLUSIONS: In
      conclusion, the rate of unexpected malignancy in open biopsies increases with
      age. It is recommended that all women above the age of 40 presenting with a
      palpable breast lump or a suspicious non-palpable abnormality on screening
      mammogram to have their lump excised even though the lump is benign on FNAC or
      CNB. However, women age of 30 to 39 should also have the lump excised in the
      presence of other risk factors such as family history of breast cancer.

PMID- 25606167
TI  - Professional training and roles of community pharmacists in malaysia: views from
      general medical practitioners.
AB  - AIM: This pilot study aimed to explore the perceptions of general medical
      practitioners (GPs) towards the professional training and roles of community
      pharmacists. METHODS: A self-administered questionnaire was distributed to all
      private clinics (n=160) run by GPs in a northern state of Malaysia. The
      instrument contained questions to evaluate the practitioners' level of agreement
      using a 5-point Likert-type scale. RESULTS: Of 160 GPs, 80 returned the
      questionnaire (response rate 50%). The respondents agreed that: GPs should
      consider the community pharmacists' recommendations whenever there is/are any
      problem(s) with the prescriptions given by them (46.3%); community pharmacists
      are the best healthcare professionals to educate patients about safe and
      appropriate use of medications (52.5%); the pharmacy profession had undergone a
      major metamorphosis from a product-oriented profession to a more patient-centred
      and outcome-oriented one (61.3%); if dispensing separation is implemented, they
      will work closely with the community pharmacists in monitoring patients'
      pharmacotherapeutic outcomes (77.5%). CONCLUSION: The current findings suggest
      that GPs would support an extension of the role of the community pharmacists in
      number of activities of patient care activities such as medication counselling.
      Thus, suggesting potential collaborative care between GPs and community
      pharmacists towards patient care and the needs to develop and incorporate topics
      on inter-professional relationship in the current medical and pharmaceutical
      education curriculums.

PMID- 25606168
TI  - High-risk behaviours and concomitant medical illnesses among patients at
      methadone maintenance therapy clinic, hospital tengku ampuan afzan, malaysia.
AB  - BACKGROUND: High prevalence of high-risk behaviours and concurrent medical
      illnesses among opioid drug users would influence the outcome of Methadone
      Maintenance Programme. It would also require a special medical attention to
      contain these issues. OBJECTIVES: This study explored patients' characteristics
      and their high-risk behaviours in order to understand more about opioid dependent
      users in Malaysia. METHODS: A total of 172 patient case notes at Methadone Clinic
      Hospital Tengku Ampuan Afzan (HTAA) were retrieved for relevant data. RESULTS:
      Many of the patients were engaged in high-risk behaviours such as needle sharing,
      unsafe sex and criminal activities. A large number of the subjects had contracted
      blood-borne diseases such as HIV and hepatitis infections. CONCLUSIONS: Education
      on the issue of medical and psychosocial complications related to high risk
      behaviours is essential. Medical professionals dealing with this group have to
      pay attention and update their knowledge on the medical issue.

PMID- 25606169
TI  - Universal versus selective screening for detection of gestational diabetes
      mellitus in a malaysian population.
AB  - OBJECTIVES: To compare the efficacy of two screenings methods for gestational
      diabetes mellitus, namely the universal screening using 50g Glucose Challenge
      Test to that of selective screening based on risk factors. METHODOLOGY: A cross
      sectional study involving 366 women between 24 weeks to 28 weeks gestation who
      attended a community health clinic for their antenatal care between January to
      May 2003. All women had their risk factors for gestational diabetes identified at
      the beginning of the study, after which they underwent a 50g Glucose Challenge
      Test and subsequently the 75g Oral Glucose Tolerance Test. RESULTS: The
      prevalence of gestational diabetes mellitus in this population was 18.3%. The
      universal screening had a sensitivity of 83.5% and specificity of 82.6% compared
      to that of selective screening, 76.1% and 60.9% respectively. Of all patients
      diagnosed to have gestational diabetes mellitus, 23.8% were without risk factors.
      CONCLUSION: Universal screening strategy using 50g glucose challenge test is a
      better predictor of gestational diabetes mellitus compared to risk-based
      selective screening.

PMID- 25606170
TI  - The management of an adolescent with conduct problems in a primary care clinic -
      a case report.
AB  - PURPOSE: To describe the management of mild conduct problems in an adolescent at
      the primary care level. CASE REPORT: A 16 year old girl presented with conduct
      problems with impending school suspension. The cause of her behavioural problems
      was mainly related to poor parenting skills of her parents and anger in herself.
      She was successfully managed with counselling and improvement of parenting styles
      in her parents. CONCLUSION: This case report illustrates the opportunity for
      family physicians to manage simple conduct problems at primary care level.

PMID- 25606171
TI  - Oral bag-valve-mask insufflation technique to remove unilateral friable nasal
      foreign body in emergency department.
AB  - Nasal foreign body in children is not an uncommon presentation to the Emergency
      Department. Removal is essential. Many methods of removal exist. Nasal wash
      technique is advocated mainly in friable foreign bodies. We report the successful
      use of the oral bag-valve-mask insufflation technique to remove friable facial
      tissue in the left nose of a 2 year-old girl. We used a pediatric bag-valve-mask
      with a pop-off pressure relief valve to avoid barotrauma. Pop-off pressure relief
      valve limits the pressure beyond 30mmHg. Conscious sedation was not required.
      There were no complications. 

PMID- 25606172
TI  - Cushing's Syndrome Secondary to Adulterated Complementary and Alternative
      Medicine.
AB  - This is a case of a 65 year old lady who presented with Cushing's syndrome
      secondary to ingestion of a complementary and alternative medicine that has been
      adulterated with exogenous glucocorticoids. In a clinical consultation, it is
      important to include assessment of complementary and alternative medicine use for
      a comprehensive care. 

PMID- 25606173
TI  - Elevated Alt and Ast in an Asymptomatic Person: What the primary care doctor
      should do?
AB  - Abnormal liver function test with raised alanine aminotransferase (ALT) and
      raised aspartate aminotransferase (AST) are commonly seen in primary care
      setting.Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH)
      and chronic viral hepatitis are common causes associated with raised ALT and
      AST.In chronic viral hepatitis, the elevation of liver enzyme may not correlate
      well with the degree of liver damage.Non-hepatic causes of raised ALT and AST
      include polymyositis, acute muscles injury, acute myocardial infarction and
      hypothyroidism.In the primary care setting, the doctor should obtain a complete
      history regarding the risk factors for viral hepatitis, substance abuse and
      request investigations accordingly.Suspected chronic viral hepatitis and liver
      cirrhosis are best referred to hepatologist for further management. 

PMID- 25606174
TI  - A right "spider" hand and a left "eagle" hand.

PMID- 25606175
TI  - Respiratory clinics: dry cough with progressively increasing breathlessness in a
      65-year old man.

PMID- 25606176
TI  - Editor's Note.

PMID- 25606178
TI  - Contact lens related corneal ulcer.
AB  - A corneal ulcer caused by infection is one of the major causes of blindness
      worldwide. One of the recent health concerns is the increasing incidence of
      corneal ulcers associated with contact lens user especially if the users fail to
      follow specific instruction in using their contact lenses. Risk factors
      associated with increased risk of contact lens related corneal ulcers are:
      overnight wear, long duration of continuous wear, lower socio-economic classes,
      smoking, dry eye and poor hygiene. The presenting symptoms of contact lens
      related corneal ulcers include eye discomfort, foreign body sensation and
      lacrimation. More serious symptoms are redness (especially circum-corneal
      injection), severe pain, photophobia, eye discharge and blurring of vision. The
      diagnosis is established by a thorough slit lamp microscopic examination with
      fluorescein staining and corneal scraping for Gram stain and culture of the
      infective organism. Delay in diagnosing and treatment can cause permanent
      blindness, therefore an early referral to ophthalmologist and commencing of
      antimicrobial therapy can prevent visual loss. 

PMID- 25606179
TI  - Photoageing skin of the elderly.

PMID- 25606177
TI  - Diabetic retinopathy and the effect of pregnancy.
AB  - Pregnancy is associated with increased risk of development and progression of
      diabetic retinopathy (DR). Although pregnancy does not have any long term effect
      on DR, progression of retinopathy changes occur in 50%-70% of cases. The greatest
      risk of worsening occurs during the second trimester and persists as long as 12
      months postpartum. The other factors found to be associated with its progression
      include duration of the diabetes, severity of retinopathy at conception,
      hyperglycaemic control, anaemia and progression of coexisting hypertension.
      Because of the increased risk of progression of the disease in pregnancy,
      conception should be delayed till the ocular disease is treated and stabilized
      and laser photocoagulation should be promptly instituted in all cases of severe
      non-proliferative retinopathy and should not be delayed till the patient develops
      early proliferative changes. Good diabetic control before and during pregnancy
      can help prevent this increase in the progression and serious vision loss. 

PMID- 25606180
TI  - Cross-sectional survey of multi-centre patient registries in malaysia.
AB  - OBJECTIVE: This survey set out to describe patient registries available in the
      country, to determine their security features, data confidentiality, extent of
      outputs produced and data quality of the registries. METHODS: A cross sectional
      survey was carried out via a self administered questionnaire. RESULTS: There were
      21 patient registries which covered important chronic diseases in health. There
      was a wide variety in duration since development, size, numbers of centre
      reporting, funding source and outputs but not much difference in data security
      and patient confidentiality amongst the registries. There were impressive outputs
      seen (reports, presentations and journal articles) and high quality data despite
      most registries being recently developed. CONCLUSION: The quality of registries
      in Malaysia is of high standard but its' major benefits have yet to be realised.

PMID- 25606181
TI  - Can Primary Care Clinic Run MMT Service Well?
AB  - Methadone Maintenance Therapy (MMT) for opiate dependence was first started in
      Malaysia in 2005. The service was initially provided by psychiatric clinics in
      hospitals and primary care clinics. Handling patients with opiate dependency
      especially in a primary care clinic is very challenging due to various
      constraints hence the success is doubtful. 143 patients from Tampin Health Clinic
      were recruited from November 2006 until March 2009. Retention rate in the program
      was high. Significant improvement was seen in the World Health Organization
      Quality Of Life score (WHOQOL-BREF) in all 4 domains done at baseline, 1st year
      and 2nd year in the program. After joining the program, there were no new blood
      borne virus infection for HIV and Hepatitis B and only 1 had Hepatitis C. Minimal
      number of patients were involved in new drug related offences while in the MMT
      program. Existing primary care clinics can be empowered to scale up this service
      in Malaysia. 

PMID- 25606182
TI  - Have we done enough with diabetic education? A pilot study.
AB  - BACKGROUND: Patients' education and empowerment are essential parts of a disease
      management. Patients have to be educated on the disease as well as lifestyle
      changes that they need to practise for a holistic and consistent improvement in
      their disease status. This study examined patients' knowledge on diabetes and
      nutrition as well as the role of dietician in the patient education. METHODS:
      This was a cross-sectional study of patients aged more than 18 years, in a
      primary care centre in Kuala Lumpur. Patients responded to a pre-tested self
      administered questionnaire which contains socio-demographic profiles of patients,
      knowledge on diabetes and nutrition. Patients were also asked on dietician
      consultation and the number of dietician visits. Patients were conveniently
      selected on the data collection days. Only consented patients and those who could
      understand Malay or English language were selected. RESULTS: There were 110
      patients who participated in the study. Overall the patients had good knowledge
      on diabetes and nutrition. The mean total knowledge score was 71.2% +/- 9.34.
      Domains such as diabetes complications, exercise, meal practice, food sources and
      proportion need reinforcement. Only 60 (54.9%) patients had seen a dietician.
      Patients who had seen dietician showed significantly higher level of knowledge
      score (p=0.04). However frequent meeting with the dietician did not show any
      significant improvement in the knowledge (p=0.10). Factors such as patients'
      gender, ethnicity, level of education, employment status, glycaemic level,
      duration of illness and body mass index did not show any significant association
      with the overall diabetic and nutrition knowledge. CONCLUSION: There is still a
      need to improve the overall diabetic education particularly in areas that
      patients were lacking such as diabetes complications, exercise, meal practice,
      food sources and proportion. It is equally necessary to encourage all diabetics
      to see a dietician since it helps to improve their level of knowledge as shown in
      this study.

PMID- 25606183
TI  - Barriers to the utilization of primary care services for mental health prolems
      among adolescents in a secondary school in malaysia.
AB  - OBJECTIVE: To study the barriers toward the utilization of primary care services
      for mental health problems among adolescents in a secondary school in Hulu
      Langat, Selangor, Malaysia. METHODS: This was a cross-sectional study conducted
      in July 2008 at a secondary school in Hulu Langat, Selangor. The respondents were
      selected using randomised cluster sampling among Form Four and Form Five
      students. Students were given self-administered questionnaire, consisting socio
      demographic data and questions on their help-seeking barrier and behaviour. Help
      seeking behaviour questions assess the use of medical facility and help-seeking
      sources. The formal help-seeking sources include from teachers, counsellors and
      doctors. The informal help-seeking sources include from friends, parents and
      siblings. RESULTS: A total of 175 students were included in the study. None of
      the students admitted of using the primary health care services for their mental
      health problems. Majority of the students were not aware of the services
      availability in the primary health care (97.1%). More than half of them thought
      the problems were due to their own mistakes (55.4%) and the problems were not
      that serious (49.1%). With regard to perception of the primary health care
      services, (43.2%) of the students were worried about confidentiality, half of
      them were concerned about other people's perception especially from their family
      members (44.6%) and friends (48.6%). Minority of them (10.8%) thought that nobody
      can help them. Few of them thought smoking (3.4%), alcohol (3.4%) and
      recreational drugs (1.1%) can solve their emotional problems. CONCLUSION: One of
      the major barriers identified in the students' failure to use the health care
      facilities was their unawareness of the availability of the service for them in
      the community. Thus there is a need to promote and increase their awareness on
      this issue.

PMID- 25606184
TI  - Prescribing of Antihypertensive Agents in Public Primary Care Clinics - is it in
      Accordance with Current Evidence?
AB  - BACKGROUND: Large population surveys in Malaysia have consistently shown minimal
      improvement of blood pressure control rates over the last 10 years. Poor
      adherence to antihypertensive medication has been recognized as a major reason
      for poor control of hypertension. This study aimed to describe the prescribing
      pattern of antihypertensive agents in 2 public primary care clinics and assess
      its appropriateness in relation to current evidence and guidelines. METHODS: A
      cross-sectional survey to describe the prescribing pattern of antihypertensive
      agents was carried out in 2 public primary care clinics in Selangor from May to
      June 2009. Hypertensive patients on pharmacological treatment for ?1 year who
      attended the clinics within the study period of 7 weeks were selected.
      Appropriate use of antihypertensive agents was defined based on current evidence
      and the recommendations by the Malaysian Clinical Practice Guidelines (CPG) on
      the Management of Hypertension, 2008. Data were obtained from patients' medical
      records and were analysed using the SPSS software version 16.0. RESULTS: A total
      of 400 hypertensive patients on treatment were included. Mean age was 59.5 years
      (SD +/-10.9, range 28 to 91 years), of which 52.8% were females and 47.2% were
      males. With regards to pharmacotherapy, 45.7% were on monotherapy, 43.3% were on
      2 agents and 11.0% were on >=3 agents. Target blood pressure of <140/90mmHg was
      achieved in 51.4% of patients on monotherapy, and 33.2% of patients on
      combination of >=2 agents. The commonest monotherapy agents being prescribed were
      beta-blockers (atenolol or propranolol), followed by the short-acting calcium
      channel blocker (nifedipine). The commonest combination of 2-drug therapy
      prescribed was beta-blockers and short-acting calcium channel blocker.
      CONCLUSION: This study shows that the prescribing pattern of antihypertensive
      agents in the 2 primary care clinics was not in accordance with current evidence
      and guidelines. beta-blockers and short-acting preparations were commonly used
      both as monotherapy and combination treatment. Thiazide diuretics, ACE inhibitors
      and long acting calcium channel blockers were underutilised in this study,
      despite robust evidence to support their use. Evidence have also shown that
      simplifying the number of daily doses is effective in improving adherence,
      therefore a wider use of generic once daily preparation should be strongly
      advocated in public primary care clinics.

PMID- 25606185
TI  - Brief report do university students have high cardiovascular risk? A pilot study
      from universiti malaysia sarawak (unimas).
AB  - A health screening was done in UNIMAS in August 2008 for 237 undergraduate
      students. Body mass index (BMI), waist circumference (WC) and blood pressure (BP)
      were measured for all subjects. Total cholesterol and glucose levels were checked
      for those who fulfilled the screening criteria. The proportion of participants
      with cardiovascular (CVD) risk factors was high. The strategies for health
      promotion should not only be targeted to the older community but also to the
      younger community. 

PMID- 25606186
TI  - Respiratory clinics: cough and melena in a 60-year-old man.

PMID- 25606187
TI  - Contact lens related corneal ulcer.

PMID- 25606188
TI  - An older woman with pain and swelling of left leg.

PMID- 25606189
TI  - Editor's Note.

PMID- 25606190
TI  - Academic mobbing: hidden health hazard at workplace.
AB  - Academic mobbing is a non-violent, sophisticated, 'ganging up' behaviour adopted
      by academicians to "wear and tear" a colleague down emotionally through
      unjustified accusation, humiliation, general harassment and emotional abuse.
      These are directed at the target under a veil of lies and justifications so that
      they are "hidden" to others and difficult to prove. Bullies use mobbing
      activities to hide their own weaknesses and incompetence. Targets selected are
      often intelligent, innovative high achievers, with good integrity and principles.
      Mobbing activities appear trivial and innocuous on its own but the frequency and
      pattern of their occurrence over long period of time indicates an aggressive
      manipulation to "eliminate" the target. Mobbing activities typically progress
      through five stereotypical phases that begins with an unsolved minor conflict
      between two workers and ultimately escalates into a senseless mobbing whereby the
      target is stigmatized and victimized to justify the behaviours of the bullies.
      The result is always physical, mental, social distress or illness and, most
      often, expulsion of target from the workplace. Organizations are subjected to
      great financial loss, loss of key workers and a tarnished public image and
      reputation. Public awareness, education, effective counselling, establishment of
      anti-bullying policies and legislations at all levels are necessary to curb
      academic mobbing. General practitioners (GPs) play an important role in
      supporting patients subjected to mental and physical health injury caused by
      workplace bullying and mobbing. 

PMID- 25606192
TI  - Brief review: who 2009 guidelines for anti-retroviral theraphy: its implication
      for primary care physician.

PMID- 25606191
TI  - Management of Chronic Heart Failure in Primary Care: What Evidence do we have for
      Heart Failure with Preserved Systolic Function?
AB  - Chronic Heart Failure (CHF) is a debilitating illness commonly encountered in
      primary care. Its prevalence in developing countries is rising as a result of an
      ageing population, and an escalating epidemic of hypertension, type 2 diabetes
      and coronary heart disease. CHF can be specifically diagnosed as Heart Failure
      with Reduced Systolic Function (HF-RSF) or Heart Failure with Preserved Systolic
      Function (HF-PSF). This paper illustrates a common presentation of HF-PSF in
      primary care; and critically appraises the evidence in support of its diagnosis,
      prognosis and management. Regardless of the specific diagnosis, long term
      management of CHF is intricate as it involves a complex interplay between
      medical, psychosocial, and behavioural factors. Hence, there is a pressing need
      for a multidisciplinary team management of CHF in primary care, and this usually
      takes place within the broader context of an integrated chronic disease
      management programme. Primary care physicians are ideally suited to lead
      multidisciplinary teams to ensure better co-ordination, continuity and quality of
      care is delivered for patients with chronic conditions across time and settings.
      Given the rising epidemic of cardiovascular risk factors in the Malaysian
      population, preventive strategies at the primary care level are likely to offer
      the greatest promise for reducing the growing burden of CHF. 

PMID- 25606193
TI  - Comparison between the panoptic ophthalmoscope and the conventional direct
      ophthalmoscope in the detection of sight threatening diabetic retinopathy: the
      kuching diabetic eye study.
AB  - OBJECTIVE: To determine the sensitivity and specificity of the conventional
      direct ophthalmoscope and the PanOptic ophthalmoscope in the detection of sight
      threatening retinopathy, as well as the "Ease of Use" of these equipments.
      METHODS: 200 diabetics, newly referred from primary health physicians were
      examined. Fundus examinations were performed with pupil dilatation in a dark
      room. The examinations were performed by a single investigator using the PanOptic
      ophthalmoscope, the conventional direct ophthalmoscope and slit lamp
      biomicroscopy. RESULTS: The overall sensitivity in detecting sight threatening
      retinopathy using the conventional direct ophthalmoscope was 73.2% (95% CI: 57.1
      85.8%), specificity 93.7% (95% CI: 88.7-96.9%). For PanOptic ophthalmoscope, the
      overall sensitivity in detecting sight threatening retinopathy was 58.5% (95% CI:
      42.1-73.7%), specificity 93.7% (95% CI: 88.7-96.9%). The conventional direct
      ophthalmoscope was 1.38 times (95% CI: 1.17-1.61 times) as easy to use compared
      to the PanOptic ophthalmoscope. CONCLUSION: The PanOptic ophthalmoscope is not
      superior to the conventional direct ophthalmoscope for the screening of Sight
      Threatening Retinopathy.

PMID- 25606194
TI  - Self reported hearing loss among elderly malaysians.
AB  - A cross-sectional study was conducted on patients attending a primary care
      facility to determine the prevalence of self reported hearing loss using a single
      question, "Do you have hearing loss?" Pure tone audiometry was performed to
      compare the accuracy of the self report. A total of 111 patients were recruited.
      The prevalence of self reported hearing loss using a single question and pure
      tone audiometry was 24.3% and 36.9% respectively. By using pure tone audiometry
      at a cut-off-level of 25 dBHL (decibels Hearing level), the single question
      yielded a sensitivity of 41.4% and specificity of 85.0%.The single question
      performed better at 40 dBHL pure tone audiometry with sensitivity of 55.0% and
      specificity of 82.0%. In conclusion, the prevalence of hearing loss in elderly
      was high and the single question self reported hearing loss performed
      satisfactorily with moderate hearing loss. 

PMID- 25606195
TI  - Visual problems of new malaysian drivers.
AB  - PURPOSE: The objective of this study was to determine the prevalence of poor
      visual acuity, colour blindness and visual field defect of new Malaysian drivers.
      METHODS: A total of 3717 new drivers (50.2% males and 49.8% females) age 19+/-6
      years, voluntarily participated in this study. Standard optometric apparatus such
      as LogMAR Charts, Ishihara plates and HandHeld Bernell Perimeter were used and
      standard procedures were applied. RESULTS: The visual examination showed 6.7%
      (n=250) of subjects achieved less than 0.3 LogMAR with better eye whilst 2.2%
      (n=83) had failed the Ishihara Test (2.1% males and 0.1% females). Most of the
      affected drivers were deutranopia. Only 2094 subjects had their visual field
      using a mobile Handheld Bernell Perimeter. 1.72% (n=36) subjects have less than
      120 degrees of peripheral field of vision. CONCLUSIONS: The visual status among
      new Malaysian drivers needs to be taken seriously to ensure safe driving. Other
      factors such as colour vision and visual field screening have to be considered
      seriously when evaluating the visual performance of a driver. Good visual
      performance is indispensible for safe driving.

PMID- 25606196
TI  - Drug reaction with herbal supplement: a possible case of drug induced lupus
      erythematosus.
AB  - A 24-year-old lady presented with four days history of fever, non-pruritic rash,
      ankle pain and swelling. She had consumed herbal supplement five days before the
      onset of symptoms. Examinations revealed erythematous maculo-papular lesions of
      varying sizes on sun exposed areas. Patient was suspected to have Drug Induced
      Lupus Erythematosus (DILE) and subsequently symptoms subsided rapidly on
      withholding the herbal medication. 

PMID- 25606197
TI  - Chronic cough with multiple causes.
AB  - This case reports a 57-year-old lady presented with cough of two months duration
      despite repeated treatments from multiple general practitioners. It took her
      another two months to know her diagnoses and a further couple of months to be
      relieved of her cough and became asymptomatic. Chronic cough management in
      primary care often needs an empiric integrative approach and requires good doctor
      patient rapport with informed follow ups and continuity of care to be successful.

PMID- 25606198
TI  - Respiratory clinics: haemoptysis, breathlessness and chest pain in a 46-year-old
      man.

PMID- 25606199
TI  - Painful oral ulcers.

PMID- 25606200
TI  - Failure to diagnose cervical cancer: what went wrong?

PMID- 25606201
TI  - Writing case reports.

PMID- 25606202
TI  - The two-minute approach to monocular diplopia.
AB  - OBJECTIVE: To describe a quick and simple diagnostic approach to monocular
      diplopia. BACKGROUND: Diplopia is a common visual complain in casualty
      departments, general practice clinics, neurologic clinics as well as ophthalmic
      clinics. Monocular diplopia, however, is uncommon. Many well established clinical
      examination methods are available to address diplopia. Some require special
      equipments which are not easily available or unfamiliar outside of ophthalmic
      clinic. We describe a simple two-minute diagnostic approach to monocular
      diplopia. CONCLUSION: Basic knowledge and understanding of simple clinical
      examination techniques enhances diagnostic skill and allow proper localization of
      underlying disorders.

PMID- 25606203
TI  - "I Am Hot, Irritable and Feeling Low; What Alternatives do I have Besides Hormone
      Replacement Therapy?".
AB  - Women at the end of their reproductive age often complain of climacteric symptoms
      which can be quite debilitating at times. Physiological changes due to deficient
      oestrogen have received global attention in the search for an acceptable and safe
      measure to improve quality of life for women with these complaints. Hormone
      replacement therapy (HRT) used to be the main treatment for menopausal symptoms.
      Lately there are concerns about its possible adverse effects of increasing risks
      of breast malignancy, heart diseases, etc. Complementary Alternative Medicine
      (CAM) plays a significant role in relieving these climacteric symptoms especially
      in women with contraindications to hormonal therapy and in those who are worried
      of its adverse effects. It is important for women to be aware of these CAM to
      provide them with options to improve their quality of life. This paper explores
      other pharmacological and non-pharmacological measures as alternatives to hormone
      replacement therapy (HRT), to assess how useful and reliable they are according
      to available scientific evidence. 

PMID- 25606204
TI  - Oral antibiotics in acne vulgaris: therapeutic response over 5 years.
AB  - INTRODUCTION: Antibiotic resistant P. acnes have influenced acne therapy
      worldwide resulting in increased use of topical and systemic retinoids. Judicious
      use of oral antibiotic is important for effective therapeutic outcome.
      OBJECTIVES: To determine the response and side effects of oral antibiotic
      treatment in acne vulgaris. To determine the type of antibiotic used, therapy
      duration and the types of concomitant topical therapy. METHODS: Retrospective
      analysis of the therapeutic response to oral antibiotics therapy in acne vulgaris
      in the Dermatology Department, Hospital Kuala Lumpur. New cases of acne vulgaris
      from 2005 to 2009 were randomly selected. The clinical notes of 250 patients
      treated with oral antibiotics were reviewed. RESULTS: About 60% of patients
      achieved good to excellent response to therapy while satisfactory response was
      seen in 26%. Only 8% patients experienced minor side effects. Doxycycline was the
      most frequently prescribed antibiotic, followed by tetracycline and erythromycin
      ethylsuccinate. The prescribing pattern was consistent over the years. The mean
      duration of treatment is four to five months. Oral antibiotic was augmented with
      topical therapy in 98.8% of patients. CONCLUSION: Good to excellent therapeutic
      response was achieved in the majority of patients and results observed have
      remained stable over the last five years.

PMID- 25606205
TI  - Diabetic hypertensive control and treatment: a descriptive report from the audit
      diabetes control and management (adcm) registry.
AB  - INTRODUCTION: Hypertension is a common co-morbidity in diabetes mellitus (DM)
      that may lead to serious complications if not adequately controlled. METHOD: This
      is a descriptive study based on data from the Audit of Diabetes Control and
      Management (ADCM) registry. This audit assessed the treatment and standard of
      control of hypertension in diabetic patients aged 18 years and above. Data were
      analysed using STATA version 9. RESULTS: From a total of 20 646 cases, about two
      third of them, 13 417 (65%) were reported to have hypertension. 19 484 (94.4%)
      had their blood pressure (BP) recorded and out of these, 11 414 (58.5%) were
      found to have BP >130/80 mmHg. 13 601 cases (65.9%) of the total sample were on
      antihypertensive drugs. 64.1% of those on antihypertensive drugs were prescribed
      angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor
      blockers. 14.2% were on more than two types of antihypertensive drugs. Older
      patients and those with longer duration of DM were less likely to achieve the
      target BP of <=130/80. In general, about 40% of diabetic cases registered in the
      ADCM project had their hypertension well controlled.

PMID- 25606206
TI  - An 80-year-old woman with left shoulder pain.
AB  - This case history illustrates the real life experience and dilemma of an 80-year
      old woman in pursuit of medical care for her left shoulder pain. Points for
      discussion range from clinical features of Pancoast tumor, importance of pain
      management, good principles of Family Medicine and Palliative care to ethical
      issues of conspiracy of silence, limited treatment plan and palliative versus
      curative radiotherapy treatment without a known biopsy report. This paper
      provides opportunity for analysis of a real complex clinical situation,
      application of medical knowledge to problem solving in clinical practice and
      relevant topics for discussions. (For anonymity sake, the names of patient,
      doctors, general and private hospitals are not mentioned. The aim of this paper
      is solely for continuous medical education without any intention to ridicule any
      party). 

PMID- 25606207
TI  - Tuberculous prostatic abscess in an immunocompromised patient.

PMID- 25606208
TI  - Parasitic infection in a young man presenting with non-specific abdominal pain.
AB  - A 27-year-old man presented with a two-week history of central colicky abdominal
      pain associated with loose stools. Further history revealed that he had been
      exposed to contaminated waters. Stool investigation by direct wet stool smears
      revealed the presence of Entamoeba histolytica and Blastocystis hominis cysts. A
      diagnosis of amoebiasis secondary to E. histolytica and concurrent B. hominis
      infestation was made. We would like to emphasise the importance of clinical
      history including recent travel to endemic areas. Any suspicion of parasitic
      infection should prompt the clinician to investigate. Early diagnosis and
      management would prevent serious complications associated with E. Histolytica
      infection. 

PMID- 25606209
TI  - Respiratory clinic: dry cough and severe weight loss.

PMID- 25606210
TI  - An adult patient with congenital heart disease.

PMID- 25606211
TI  - An Elderly Woman with Unresolved 'Stye' Over her Right Lower Eye Lid.

PMID- 25606212
TI  - A guide on guidelines.

PMID- 25606213
TI  - Obstructive sleep apnoea hypopnea syndrome - an overview.
AB  - Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is a common cause of
      breathing-related sleep disorder, causing excessive daytime sleepiness. Common
      clinical features of OSAHS include snoring, fragmented sleep, daytime somnolence
      and fatigue. This article aims to provide a comprehensive review of the
      condition, including its management. 

PMID- 25606214
TI  - Effectiveness of computerized visual screening tool used in driving schools in
      malaysia.
AB  - PURPOSE: A survey on new Malaysian drivers was conducted in Malaysia between year
      2006-2009. The objective of this study was to look at the effectiveness of the
      present computerized visual screening tool and to compare it with the
      conventional testing method. METHODS: A total of 3717 drivers aged 19+/-6 years,
      who had passed in the computerized visual screening, participated in this study.
      RESULTS: 250 subjects achieved less than 0.3 LogMAR with their best eye and 83
      subjects failed the Ishihara Test after retested using the conventional tool.
      CONCLUSION: These finding showed the computerized visual screening test failed to
      filter some subjects according to the standards set.

PMID- 25606215
TI  - A comparison of morbidity patterns in public and private primary care clinics in
      malaysia.
AB  - OBJECTIVES: To compare the morbidity patterns in public and private primary care
      clinics; determine patients' reasons for encounter (RFE) and diagnoses using the
      ICPC-2, and compare ten commonest diagnoses and RFEs. METHODS: A cross-sectional
      study on randomly selected clinics was conducted nationwide. Doctors completed
      the Patient Encounter Record (PER) for systematically selected encounters for a
      week. RESULTS: Response rate was 82.0% (public clinic) and 33% (private clinic)
      with 4262 encounters and 7280 RFE. Overall, the three commonest disease
      categories encountered were respiratory (37.2%), general and unspecified (29.5%),
      and cardiovascular diseases (22.2%). Public and private clinics handled 27%
      versus 50% acute cases and 20.0% versus 3.1% chronic cases i.e. 33.7 and 5.6
      chronic diseases per 100 RFE respectively. CONCLUSION: Doctors in public clinics
      saw more chronic and complex diseases as well as pregnancy related complaints and
      follow-up cases while in private clinics more acute and minor illnesses were
      seen. Health services should be integrated and support given to co-manage chronic
      diseases in both sectors.

PMID- 25606216
TI  - Palliative care for a child: role of a primary care doctor.
AB  - A 7-year-old boy with a diagnosis of advanced medulloblastoma refractory to
      treatment was discharged from hospital for further palliative care at home.
      During this short and eventful period, the child developed spinal cord
      compression with progressive weakness of upper and lower limbs, neck pain, faecal
      and urinary incontinence. This case highlights the important roles of a primary
      care doctor in the provision of palliative care for a child in the community. 

PMID- 25606217
TI  - The blue man who presented with a stroke.
AB  - A 19-year-old man presented with sudden onset of right eye ptosis, diplopia and
      giddiness. He had no previous medical illnesses with negative history of
      exertional dyspnoea, epistaxis, haemoptysis, palpitations, chest pain and chronic
      cough. Examination revealed central cyanosis, digital clubbing, polycythaemia,
      partial ptosis of right eye, diplopia on right gaze and dilated right pupil.
      Examination of the chest revealed pectus excavatum but no cardiac murmurs were
      heard. Investigations revealed a solitary right pulmonary arteriovenous
      malformation with two feeder vessels which were successfully embolized
      surgically. 

PMID- 25606218
TI  - Pre-auricular sinus: an uncommon presentation.
AB  - An infected pre-auricular sinus presenting as a post-auricular swelling is
      commonly misdiagnosed as an infected dermoid or sebaceous cyst. It may even mimic
      a mastoid abscess leading to further unwarranted investigations and
      interventions. We present a case of a 25-year-old Malay man who was initially
      diagnosed with recurrent infected dermoid cyst. At presentation, a right post
      auricular inflamed swelling was noted with an overlying old incision and drainage
      scar. An auricular pit was found at the crus of helix. Using a blunt probe
      inserted along the sinus tract pus was drained without the need for further
      surgical incision. Six weeks after the acute episode, patient underwent excision
      of the pre-auricular sinus with no evidence of recurrence at three months follow
      up. Awareness by the attending physician of this 'variant type' of pre-auricular
      sinus at patient's first presentation may negate the need for unnecessary
      incision and drainage which may subsequently impact the outcome of surgical
      excision and reduce the risk of recurrence. 

PMID- 25606219
TI  - An adult patient with nail abnormality.

PMID- 25606220
TI  - A clerk with back pain.

PMID- 25606221
TI  - A still born baby with cranial vault defects.

PMID- 25606222
TI  - Management of hypertension.

PMID- 25606223
TI  - Acute grief with delirium in an elderly: holistic care.
AB  - Delirium in the elderly is a challenging and under-recognized problem in the
      community. Early detection and management improves outcomes and quality of life
      for the elders with delirium at home.1 Family physicians (FP) play a key role in
      the assessments, early identification, and management of delirium and in the
      support and education of patients and their family caregivers.1 Clinical analysis
      of this case illustrates the bio-psychosocial spiritual model of approach to
      management of delirium in an elderly patient in the home setting. 

PMID- 25606224
TI  - Brief report: nail sampling technique and its interpretation.
AB  - The clinical suspicion of onychomyosis based on appearance of the nails, requires
      culture for confirmation. This is because treatment requires prolonged use of
      systemic agents which may cause side effects. One of the common problems
      encountered is improper nail sampling technique which results in loss of
      essential information. The unfamiliar terminologies used in reporting culture
      results may intimidate physicians resulting in misinterpretation and hamper
      treatment decision. This article provides a simple guide on nail sampling
      technique and the interpretation of culture results. 

PMID- 25606225
TI  - Risk factors for diabetic retinopathy in diabetics screened using fundus
      photography at a primary health care setting in East malaysia.
AB  - INTRODUCTION: This study reports on the prevalence of diabetic retinopathy (DR)
      and risk factors among diabetic patients, who underwent fundus photography
      screening in a primary care setting of Borneo Islands, East Malaysia. We aimed to
      explore the preliminary data to help in the planning of more effective preventive
      strategies of DR at the primary health care setting. MATERIALS AND METHODS: A
      cross-sectional study on 738 known diabetic patients aged 19-82 years was
      conducted in 2004. Eye examination consists of visual acuity testing followed by
      fundus photography for DR assessment. The fundus pictures were reviewed by a
      family physician and an ophthalmologist. Fundus photographs were graded as having
      no DR, NPDR, PDR and maculopathy. The data of other parameters was retrieved from
      patient's record. Bi-variate and multivariate analysis was used to elucidate the
      factors associated with DR. RESULTS: Any DR was detected in 23.7% (95% CI=21 to
      27%) of the patients and 3.2% had proliferative DR. The risk factors associated
      with any DR was duration of DM (OR =2.5, CI=1.6 to 3.9 for duration of five to 10
      years when compared to <5 years) and lower BMI (OR=1.8, CI=1.1 to 3.0). Moderate
      visual loss was associated with DR (OR=2.1, CI=1.2 to 3.7). CONCLUSIONS: This
      study confirms associations of DR with diabetic duration, body mass index and
      visual loss. Our data provide preliminary findings to help to improve the
      screening and preventive strategies of DR at the primary health care setting.

PMID- 25606226
TI  - Prevalence of smoking among secondary school students in sarawak.
AB  - Adolescent smoking is an emerging health concern in the developing countries. A
      cross-sectional study is conducted to determine the prevalence and smoking
      behaviour of adolescents in Sarawak. The prevalence of smoking is 32.8% with mean
      age of initiation at 12.8+/-1.9 years. Most (67.2%) adolescents are experimental
      smokers and the majority (67.9%) did not smoke on a daily basis. Branded
      cigarettes are preferred (83.1%) and the cigarettes are obtained either from
      friends (49.1%) or self purchased (43.6%). Students prefer to smoke at their
      friend's house (31.0%) or at school (25.3%). Smoking prevalence among adolescents
      in Sarawak is high and begins early. Early intervention on smoking prevention and
      risk awareness is perhaps more effective if initiated before the age of 12 years.

PMID- 25606227
TI  - Paediatric ocular trauma in kuching, sarawak, malaysia.
AB  - PURPOSE: To evaluate the demography, aetiology, type and outcome of paediatric
      ocular trauma in tertiary centre in Malaysia. METHOD: We retrospectively studied
      118 eyes from 117 patients over a period of 36 months (January 2006 to December
      2008). All ocular injuries in patients aged 12 and below seen in the
      Ophthalmology Department for the first time were included in this study. RESULTS:
      Mean age of patients was 6.1+/-3.0 years. 68 cases (58.2%) occurred in pre-school
      children, whereas 49 (41.9%) in school-aged children. Boys accounted for 65.8% of
      cases. There was no predilection for either right or the left eye. 47% of cases
      (56 patients) occurred in Malay. Most of the injuries took place at home when the
      children were alone (p<0.05). Sharp objects were the commonest cause (45 cases,
      38.1%). The majority of cases (103, 87.3%) were considered preventable. The
      frequency of open and closed globe injury was similar. Hyphema was more common in
      closed globe injury compared to open globe injury (p<0.05). Other associated
      injuries such as cataract, vitreous hemorrhage and retinal hemorrhage are similar
      between the two groups. Visual outcome is generally poor with only 34 eyes
      (28.8%) had no visual impairment. CONCLUSION: Ocular trauma in children is an
      important cause of visual loss. Most cases occurred at home and were preventable.
      Prevention through education is the best approach.

PMID- 25606228
TI  - Clinical characteristics of gout: a hospital case series.
AB  - INTRODUCTION: Gout is an increasingly common medical problem. The traditional
      risk factors of male sex and high red meat or alcohol consumption have been
      joined with newer risks such as increased life expectancy, and the metabolic
      syndrome (hypertension, diabetes, dyslipidaemia, truncal obesity). METHODS: This
      was a retrospective study to determine the epidemiology, clinical features,
      associated conditions as well as renal related conditions in existing gout
      patients followed-up in Rheumatology outpatient clinic, Hospital Tuanku Ja'afar,
      Seremban. RESULTS: Over a three month period, we identified 54 gouty patients on
      our follow-up, the majority being male, Malay ethnicity, with the age of onset in
      the third and fourth decades of life. Commonly associated risk factors were
      hypertension, hyperlipidaemia and obesity. However, underlying history of
      diabetes mellitus, alcohol consumption, and family history were not commonly
      associated with gout in our group of patients. Half of our patients had at least
      two or more joints involvement. About half of the patients with tophaceous gout
      had renal impairment. CONCLUSION: Our series of gout patients highlight the high
      prevalence of cardiovascular risk factors. The high prevalence of tophi and renal
      impairment is a cause for concern.

PMID- 25606229
TI  - Diagnosis and Management of Mild Cognitive Impairment in the Community: What is
      the Role of Primary Care Physician?
AB  - Dementia is a large and growing problem in the ageing population but often not
      diagnosed in its earlier stages which is Mild Cognitive Impairment (MCI). MCI
      represents the phase between normal ageing and early dementia. About 12% of
      patients with MCI develop dementia per year, usually Alzheimer's disease. It is a
      diagnosis given to individuals who have cognitive impairments beyond that is
      expected for their age and education. However, this condition does not interfere
      significantly with daily activities as these individuals retain their critical
      thinking and reasoning skills. Nevertheless, due to its complexity and vague
      initial presentation, many cases of MCI can be missed. Therefore, it is
      imperative for primary care physicians to recognise these symptoms as opposed to
      normal ageing memory changes, and refer these patients to the memory clinic early
      to confirm the diagnosis. This paper illustrates a common primary care
      presentation of a patient with MCI. As there is no proven pharmacological
      treatment for MCI, the mainstay of management is to provide lifestyle
      intervention and long term support to these patients in the community. Primary
      care physicians should work as a team with the geriatrician, allied health
      personnel, support groups and caregivers in providing this care. 

PMID- 25606230
TI  - An adolescent with anorexia nervosa - a case report.
AB  - This case report illustrates an adolescent with clinical presentation of moderate
      anorexia nervosa with no significant co-morbidities. It highlights the management
      of anorexia nervosa in the outpatient setting by a multi-disciplinary health care
      team which includes a family physician, a dietician, a psychologist and a child
      psychiatrist. 

PMID- 25606231
TI  - A child with epistaxis, reduced hearing and cervical lymphadenopathy: a rare case
      of nasopharyngeal carcinoma in a child.
AB  - Although nasopharyngeal carcinoma (NPC) is common in this part of the world, the
      incidence among children is still very low worldwide. The diagnosis is sometimes
      delayed because of the late reporting of the symptom by the patient or parents,
      or difficulty in reaching the final diagnosis due to its hidden anatomical
      location. The challenges include the difficult endoscopy in children, inability
      to differentiate an adenoid from the tumour on radiograph and often the
      inconclusive fine needle aspiration findings. If the tumour mass at Fossa of
      Rosenmuller can be clearly appreciated and biopsied with undoubtedly proven
      histology of NPC, the diagnosis can be straight forward and treatment can be
      commenced as early as possible. We report a 10-year-old child presented with
      bilateral neck cervical lymphadenopathy and epistaxis with fine needle aspiration
      cytology (FNAC) of the neck mass reported as lymphoma. Further work-up confirmed
      he was suffering from NPC. 

PMID- 25606232
TI  - Role of mantoux test in the diagnosis of tuberculosis.

PMID- 25606234
TI  - Management of schizophrenia in adults.

PMID- 25606233
TI  - An elderly smoker with abnormal chest film.

PMID- 25606235
TI  - Coining: an ancient treatment widely practiced among asians.
AB  - Coining is a technique used in treating many illnesses since ancient times. It is
      a form of dermabrasion therapy still widely practiced in China and South East
      Asia. This ancient treatment method is employed to rid the body of "heatiness" or
      "negative energies". Coining is associated with serious complications, and has
      been confused with child abuse by physicians unfamiliar to Asian cultures.
      Despite the availability of more simple and effective treatment for fever,
      coining is still widely practiced among Asians. 

PMID- 25606236
TI  - Editor's Note.

PMID- 25606237
TI  - An annual audit of the ear foreign bodies in hospital universiti sains malaysia.
AB  - Foreign bodies or objects in the ear are one of the most common problems
      encountered by otorhinolaryngologist (ORL) with attendant complications, removal
      of which requires expertise. Patients with this problem who sought treatment in
      the otorhinolaryngology clinic of Hospital Universiti Sains Malaysia (HUSM) were
      studied for duration of one year from January 2010 to December 2010.
      Specifically, the clinical presentation, type of foreign body and management
      outcome were analysed. 72 patients were reviewed - 44 (61.1%) males and 28
      (38.9%) females. The age range was one year to 75 years with 59.8% being children
      below 10 years old. Ear pain (56.9%) was recorded as the most common and
      persistent symptom and insects (54%) were the commonest foreign body encountered.
      95% (69) of the foreign bodies were removed under clinic setting with only three
      (4.2%) cases requiring general anaesthesia. Post-removal complications were noted
      in only one patient (1.4%). Repeated attempts by untrained personnel should be
      avoided and timely referral is vital to avoid undesirable complications. 

PMID- 25606238
TI  - Prevalence of eye diseases and visual impairment among the rural population - a
      case study of temerloh hospital.
AB  - OBJECTIVE: To determine the prevalence of eye diseases and visual impairment
      among new patients at the eye clinic of Hospital Sultan Haji Ahmad Shah,
      Temerloh, Pahang. METHOD: In this cross-sectional prospective study, 1081 new
      patients were examined over a period of six months. Age, gender, ethnicity,
      visual acuity and diagnosis were noted from the medical records. RESULTS: Out of
      1081 examined, 607 (56.1%) were males, 783 (72.4%) were Malays. The mean age of
      patients was 45.2 years (ranging from one month to 91 years). Cataract (248,
      22.9%) was the most common eye disease, followed by retinal diseases (124, 11.5%)
      and ocular trauma (106, 9.8%). Majority of the patients (48) suffering from
      ocular trauma had foreign body cornea. In 85 premature infants screened for
      retinopathy, 19 showed different stages of retinopathy of prematurity. Visual
      impairment was noted in 89 (8.2%) patients, severe visual impairment in 12 (1.1%)
      and blindness in 35 (3.2%); vision could not be determined in 85 premature
      infants (7.9%). Cataract was singled out as the cause of severe visual impairment
      in 11 out of 12 patients. CONCLUSION: Health education at primary health centres
      and availability of eye specialists in all the district hospitals will facilitate
      the rehabilitation of visually impaired and blind persons by providing early
      treatment for eye problems (specifically prescription for spectacles, medical
      treatment and cataract surgery with intraocular lens implantation).

PMID- 25606239
TI  - A study on pregnant adolescents residing in a government home: common
      characteristics and their views on the pregnancy.
AB  - BACKGROUND: Adolescent pregnancy has emerged to be a significant public health
      and social issue in Malaysia as its prevalence is increasing in our population.
      OBJECTIVES: This study aimed to identify the common characteristics of pregnant
      adolescents residing in a government shelter home. Their reasons for pregnancy,
      sources of information on contraception, and views on abortion and future care of
      the baby were explored. METHODS: A cross-sectional study was performed on 26
      universally sampled pregnant adolescents in the centre. The adolescents responded
      to a set of self-administered questionnaire on their socio-demographic profiles,
      reasons of their pregnancy, contraception and future plans including abortion as
      well as care of the newborn. RESULTS: Almost all (92%) of the adolescents were
      unmarried. Majority of them were in late adolescence, age between 16 to 19 years
      (73.1%), from urban areas (73.1%) and of low income families (53.8%). There were
      69.3% of the adolescents who were school dropouts. The reasons for pregnancy were
      consensual sexual activity (63.0%), coercion by boyfriend (18.5%), and rape
      (11.5%). The main sources of information on contraception were friends (50%),
      partners (50%) and the internet or mass media (42.3%). 54% had considered
      abortion earlier, but majority (92.0%) disagreed that abortion should be
      legalised in Malaysia. Most of the adolescents planned to parent their child with
      or without help from significant others and only 42.3% planned to relinquish
      their child for adoption. CONCLUSION: To curb teenage pregnancy-related problems,
      efforts on educating the adolescents about sexual reproductive health and
      assertive communication skills should be implemented, especially to the late
      adolescents, school dropouts and those from poor urban families. Parenthood
      support may be necessary to the pregnant adolescents who opted to care for their
      own child.

PMID- 25606240
TI  - An examination of Australian general practitioners' knowledge, attitudes and
      practices in relation to sleep disorders.
AB  - BACKGROUND: Sleep disorders represent an under-recognised public health problem
      and are reported to be under-diagnosed in general practices. AIMS: To examine
      general practitioners' (GPs) attitude, knowledge and practice behaviour and
      identify barriers to detection, diagnosis and treatment of sleep disorders
      encountered in the Australian primary care setting. METHOD: Using mixed methods,
      quantitative data from the Dartmouth Sleep Knowledge Questionnaire (DSKQ) were
      analysed using MS Excel 2007. Qualitative data were obtained from one focus group
      and eight interviews. Data were thematically analysed. RESULTS: 15 GPs
      participated; seven in a focus group and eight in interviews. Scores from DSKQ
      suggest gaps in GPs' knowledge. Qualitative analysis revealed that patients
      frequently presented with sleep disorders underpinned by mental health disorders.
      GPs agreed that prescribing pharmacological interventions was undesirable and
      behavioural interventions were preferred. Barriers included limited training for
      GPs, lack of resources, patient expectations and willingness to engage in
      lifestyle changes, and consultation time constraints. DISCUSSION: Greater
      flexibility to investigate sleep related problems within the standard
      consultation and improved access to educational activities could assist GPs.
      Patient factors, such as adherence to management strategies, are paramount to
      successful management of sleep disorders; however, these obstacles to clinical
      practice may be difficult to overcome. CONCLUSION: Providing education for GPs
      about sleep disorders, greater flexibility within consultations may improve
      patient care and patient engagement in management strategies may assist, yet a
      critical success factor in disease management includes patient engagement in
      management strategies.

PMID- 25606242
TI  - Unilateral foul smelly nasal discharge in an adult.
AB  - The incidence of rhinolith is by far very low compared to the nasal foreign
      bodies, especially in adult. Foreign body (FB) in the nostril will lead to
      unilateral nasal symptom which can start with nasal obstruction or discomfort. In
      younger children, they may miss to report the problem to the parents but, later
      on, the FB will manifest itself with unilateral nasal discharge, which at most of
      the time fouls smells. We report a case of a healthy adult female who presented
      with unilateral foul smelly nasal discharge which later was diagnosed as
      rhinolith, with rubber-tip pencil eraser as the nidus of calcification. 

PMID- 25606241
TI  - Vaginismus and subfertility: case reports on the association observed in clinical
      practice.
AB  - OBJECTIVE: To analyse the features of patients with vaginismus first presented to
      a gynaecologist for infertility before being referred for psychiatric evaluation
      and management. The case series aim to provide some insight on features and
      presentations of Asian women with vaginismus. Vaginismus is characterised by
      persistent or recurrent difficulties in vaginal penetration despite the woman's
      wish for coitus. Avoidance, phobia, anticipatory fear of pain and involuntary
      pelvic muscle contraction are the most common symptoms. METHOD: We report a
      series of cases of Malaysian women who had been suffering from vaginismus and
      'infertility'. All the cases had never been attended to medically and there were
      long delays in seeking intervention. There was no history of traumatic sexual
      experience or any major psychiatric illness in these patients. Majority of the
      patients had prominent symptoms of anxiety. CONCLUSION: The cases illustrate that
      it is important to rule out the possibility of vaginismus among patients with
      infertility. The former have unique psychological features which require
      psychological interventions.

PMID- 25606243
TI  - Ptosis due to cavernous sinus syndrome as a rare presentation of advanced breast
      metastasis in a patient with delayed diagnosis.
AB  - Complications of breast cancer metastasis may be the first manifestation of the
      disease. We report a rare case of left eye ptosis secondary to cavernous sinus
      syndrome in a 34-year-old lady due to refusal of proper medical treatment for
      metastatic breast cancer. The delay in seeking medical treatment was attributed
      to her use of Traditional Chinese Medicine (TCM). 

PMID- 25606244
TI  - Respiratory Clinics: MEDIASTINAL SHIFT: A SIGN OF SIGNIFICANT CLINICAL AND
      RADIOLOGICAL IMPORTANCE IN DIAGNOSIS OF MALIGNANT PLEURAL EFFUSION.

PMID- 25606245
TI  - Issues in emergency contraception for the adolescent.

PMID- 25606246
TI  - A man with hot potato voice and neck swelling.

PMID- 25606247
TI  - An elderly lady with blurring of vision.

PMID- 25606249
TI  - Editor's Note.

PMID- 25606248
TI  - A man with multiple abdominal calcifications.

PMID- 25606250
TI  - Prevalence and determinants of left ventricular hypertrophy in hypertensive
      patients at a primary care clinic.
AB  - Left ventricular hypertrophy (LVH) has prognostic significance on cardiovascular
      mortality and morbidity. However, echocardiography screening for LVH is not
      routinely done for hypertensive patients in a primary care setting. Thus, this
      quantitative study aims to determine the prevalence and factors associated with
      LVH in hypertensive patients at a primary care setting. This was a cross
      sectional study of 359 consecutive patients with uncomplicated essential
      hypertension attending a hospital-based clinic in Malaysia. All subjects
      underwent an echocardiography test. LVH occur when the left ventricular posterior
      wall thickness together with inter-ventricular septal thickness is >=11 mm. It
      was found that 24% patients fulfilled the criteria for LVH. The mean age of the
      study population was 59.2+/-7.7 years; mean duration of hypertension was 9.7+/
      7.5 years; and mean blood pressure was 136.5/81.5 (+/-13.7/7.7) mmHg. Using
      multiple logistic regression analysis, patients who were obese [odds ratio (OR)
      8.34, 95% confidence interval (CI) 3.14, 22.22] and male gender (OR 1.96, 95% CI
      1.08, 3.16) had significant positive association with LVH. LVH was found in
      approximately one fourth of the hypertensive patients at a hospital-based primary
      care setting. There was a significant positive association between LVH and
      obesity and being male. Guidelines for enhancing use of echocardiography in
      detecting LVH may be needed. 

PMID- 25606251
TI  - Reliability and Validity of the Revised Summary of Diabetes Self-Care Activities
      (SDSCA) for Malaysian Children and Adolescents.
AB  - BACKGROUND: Self-care plays an important role in diabetes management. One of the
      instruments used to evaluate self-care in patients with diabetes is the Summary
      of Diabetes Self-Care Activities (SDSCA) questionnaire. A validated instrument in
      the Malay language is used to assess self-care practice among children and
      adolescents with diabetes in Malaysia. OBJECTIVE: To translate and evaluate the
      psychometric properties of the revised version of the SDSCA questionnaire in the
      Malay language. METHODS: Forward and backward translations were performed. An
      expert panel reviewed all versions for conceptual and content equivalence. The
      final version was administered to paediatric patients with diabetes between
      August 2006 and September 2007. Reliability was analysed using Cronbach's alpha
      and validity was assessed using exploratory factor analysis. RESULTS: A total of
      117 patients aged 10-18 years were enrolled from nine hospitals. The reliability
      of overall core items was 0.735 (with item 4) while the reliabilities of the four
      domains were in the range of 0.539-0.838. As core item number 4 was found to be
      problematic and it was subtituted by item 5a (from the expanded SDSCA) to suit
      local dietary education and practice; and the reliabilities of the overall core
      item (0.782) and the four domains (0.620 - 0.838) improved. Factor loadings of
      all the items were greater than 0.4, loaded into the original domains, and
      accounted for 73% of the total variance. CONCLUSION: The Malay translation of the
      revised English SDSCA is reliable and valid as a guide for Malaysian children and
      adolescents suffering from diabetes.

PMID- 25606252
TI  - Perception of Quality of Life among People with Diabetes.
AB  - Diabetes is a chronic disease that affects a patient's quality of life. This
      cross-sectional study aimed to determine the socio-demographic and disease
      profile factors associated with poor quality of life among patients with
      diabetes. The study was conducted at a primary health care clinic in Kuching
      between August to November 2010. Short Form - 36 (SF - 36) questionnaire was used
      to assess the quality of life of diabetic patients aged >= 18. A total of 142
      respondents participated in the survey. After adjusting for age, those with no
      education scored lower at vitality (p=0.043) and emotional health (p=0.033)
      compared with those who have tertiary education. Those working in the private
      sector scored better for physical functioning (p=0.042) compared with pensioners
      and the unemployed. Patients with uncontrolled diabetes scored lower in the role
      emotional domain (p=0.003). Participants who were on <3 (p=0.014) and >=3
      (p=0.024) oral medications had better score for role-physical than those on
      insulin. Those on insulin had worse score for bodily pain than those on oral
      medication only (vs <3 oral drugs, p=0.026; vs >=3 oral drugs, p=0.001). Various
      socio-demographic factors, uncontrolled diabetes and insulin usage were found to
      have negative impact on a diabetic patient's quality of life. Programmes
      addressing the physical and emotional needs of diabetic patients at the primary
      health care setting are essential to help improve their quality of life. 

PMID- 25606253
TI  - An audit of sputum smear negative pulmonary tuberculosis cases in kinta district,
      perak, in 2011.
AB  - 58 cases of sputum smear negative pulmonary tuberculosis (PTB) were reported to
      Kinta Health Department between January and June 2011. It was found that 47 cases
      (81%) were sputum smear negative cases. Six cases (10.3%) were actually sputum
      smear positive but were wrongly reported as smear negative. Five cases (8.6%)
      were misdiagnosed as tuberculosis. Majority of these patients (82.7%) sought
      consultation and treatment after two weeks of having cough. Only 6.9% sought
      treatment for cough that was less than two weeks old. Accurate diagnosis of PTB
      is crucial and the Perak State Health Department needs to quickly adopt steps to
      improve the situation. 

PMID- 25606254
TI  - Cat's Curse: A Case of Misdiagnosed Kerion.
AB  - Kerion is an inflammatory type of tinea capitis which can be mistaken for
      bacterial infection or folliculitis as both conditions display similar clinical
      features. It occurs most frequently in prepubescent children and rarely in
      adults. We report a 26-year-old woman who presented with multiple tender
      inflammed nodules on her scalp. Her condition was misdiagnosed as bacterial
      abscess and treated with multiple courses of antibiotics without improvement.
      Later, her condition was re-diagnosed as kerion based on clinical appearance,
      history of contact with infected animal and Wood's lamp examination. symptoms and
      lesions resolved completely with systemic antifungal treatment leaving residual
      scarring alopecia. The delay in the diagnosis and treatment of this patient
      resulted in permanent scarring alopecia. 

PMID- 25606255
TI  - Nasopharyngeal (Tornwaldt's) Cyst: Rare Finding in a Habitual Snorer.
AB  - A nasopharyngeal (Tornwaldt's) cyst is uncommon. It is often asymptomotic;
      however it may cause problem if it too big becomes. We present a case of a 24
      year-old Malay girl who had been a habitual snorer for years but was unaware of
      the significance of her problem. Opportunities for an earlier referral and
      assessment were missed since we were not aware of her history despite previous
      related but non-specific consultations at our primary healthcare centre. She was
      referred to us a few years later when her nasopharyngeal cyst became infected.
      After a course of antibiotics, she proceeded with an endoscopic resection of the
      nasopharyngeal cyst. A follow-up visit six months later did not reveal a
      recurrence. This case highlights the importance of a good history for the
      diagnosis of a nasopharyngeal cyst. 

PMID- 25606256
TI  - A successful antenatal myomectomy.
AB  - Complications that may occur while performing myomectomy in pregnancy can be
      prevented in a well-optimised surgery. Counselling and comprehensive peri
      operative preparations are mandatory to minimise litigations and untoward events.
      Myomectomy in pregnancy remains a contentious issue. Degeneration of fibroid
      during pregnancy is common. However, conservative management suffices in majority
      of cases. In non-responsive conservative treatment, myomectomy may be an option.
      This article discusses our experience in treating a 38-year-old woman in her
      fourth pregnancy at 15 weeks gestation with symptomatic uterine fibroid. She had
      persistent abdominal pain since nine weeks gestation. She developed fever and
      acute abdomenat at 15 weeks and the uterus was larger than dates.Ultrasound scan
      confirmed single pregnancy with a large intramural fibroid showing degenerative
      changes. A myomectomy was performed as a preventive measure to prevent massive
      haemorrhage. Although performing myomectomy during pregnancy is considered
      controversial, complications can be minimised with properly-planned surgery. 

PMID- 25606257
TI  - Vitamin B12 deficiency presenting as pancytopenia in pregnancy: a case report.
AB  - Vitamin B12 deficiency is a well-known cause of megaloblastic anaemia and
      pancytopenia. However, the incidence in pregnancy is rarely reported. We present
      a case of a 32-year old multigravid woman who was diagnosed with megaloblastic
      anaemia since 22 weeks gestation and progressed to develop severe pancytopenia at
      30 weeks gestation. She was also diagnosed with vitamin B12 deficiency related to
      dietary and sociocultural habits. Folate and iron levels were normal throughout
      pregnancy. Treatment with parenteral cyano-cobalamin resulted in sustained
      improvement of haematological parameters. The pregnancy was carried to term and
      the baby was born weighing 2,050gm but otherwise well at birth and had normal
      developmental milestones thereafter. This case illustrates the clinical
      presentation of maternal vitamin B12 deficiency and demonstrates the importance
      of detecting and treating maternal vitamin B12 deficiency during pregnancy in at
      risk patients. Failure to diagnose and institute treatment carries significant
      risks to both mother and child. Oral vitamin B12 supplementation should be
      considered for patients who are strict vegetarians or consume very little animal
      products. 

PMID- 25606258
TI  - Ludwig's Angina: The Importance of Oral Cavity Examination in Patients with a
      Neck Mass.
AB  - Neck mass is a common condition in primary care. The most common affected area is
      the cervical lymph node. The neck region is also prone infection as structurally
      the nodes and spaces are in close contact with the upper respiratory tract and
      the alimentary tract. Oral cavity is one of the most common route for harbouring
      infection. Poor oral hygeine and periapical dental problems are the main causes.
      Thus, it is important to perform a complete oral cavity examination even when
      trismus is present. Besides dental caries, floor of the mouth should be inspected
      for oedema that may impose threat to the upper airway. We report a case of
      Ludwig's angina originating from a periapical lesion of the lower molar stressing
      the importance of oral examination in patient with neck mass. 

PMID- 25606259
TI  - Publication ethics.

PMID- 25606260
TI  - Validating instruments of measure : Is it really necessary?

PMID- 25606261
TI  - Validation of the Malay version of Berlin questionaire to identify Malaysian
      patients for obstructive sleep apnea.
AB  - OBJECTIVE: To validate the Malay version of Berlin Questionnaire (BQ) as a tool
      to screen for patients at risk of obstructive sleep apnea (OSA) in primary care.
      BACKGROUND: Most patients with OSA are unrecognised and untreated. Thus, the BQ
      has been used as a tool to screen for patients at risk for OSA. However, this
      tool has not been validated in Malay version. MATERIALS AND METHODS: A parallel
      back-to-back translation method was applied to produce the Malay version (Berlin
      M). The Malay version was administered to 150 patients in a tertiary respiratory
      medical centre.  Concurrent validity of the Berlin-M was determined using the
      Apnea Hypopnea Index (AHI) as the gold standard measure.  The test-retest
      reliability and internal consistency of the Berlin-M were determined. RESULTS:
      Most patients were males (64.0%) and majority of them were Malays (63.3%). Based
      on the sleep study test, 121 (84.0%) were classified as high risk while 23
      (16.0%) as low risk using the Apnea Hypopnea Index (AHI) >=5 as the cutoff point.
      The test-retest reliability Kappa value showed a good range between 0.864 -
      1.000. The Cronbach's alpha of BQ was 0.750 in category 1 and 0.888 in category
      2. The sensitivity and specificity were 92% and 17% respectively. CONCLUSION: The
      BQ showed high sensitivity (92%) but low specificity (17%). Therefore, though the
      Berlin-M is useful as a screening tool, it is not a confirmatory diagnostic tool.

PMID- 25606262
TI  - Reliability and validity of the Malay translated version of diabetes quality of
      life for youth questionnaire.
AB  - INTRODUCTION: Many studies reported poorer quality of life (QoL) in youth with
      diabetes compared to healthy peers. One of the tools used is the Diabetes Quality
      of Life for Youth (DQoLY) questionnaire in English. A validated instrument in
      Malay is needed to assess the perception of QoL among youth with diabetes in
      Malaysia. OBJECTIVE: To translate the modified version, i.e., the DQoLY
      questionnaire,into Malay and determine its reliability and validity. METHODS:
      Translation and back-translation were used. An expert panel reviewed the
      translated version for conceptual and content equivalence. The final version was
      then administered to youths with type 1 diabetes mellitus from the universities
      and Ministry of Health hospitals between August 2006 and September 2007.
      Reliability was analysed using Cronbach's alpha, while validity was confirmed
      using concurrent validity (HbA1c and self-rated health score). RESULTS: A total
      of 82 youths with type 1 diabetes (38 males) aged 10-18 years were enrolled from
      eight hospitals. The reliability of overall questionnaire was 0.917, and the
      reliabilities of the three domains ranged from 0.832 to 0.867. HbA1c was
      positively correlated with worry (p=0.03). The self-rated health score was found
      to have significant negative correlation with the "satisfaction" (p=0.013) and
      "impact" (p=0.007) domains. CONCLUSION: The Malay translated version of DQoLY
      questionnaire was reliable and valid to be used among youths with type 2 diabetes
      in Malaysia.

PMID- 25606263
TI  - Generalised pruritus as a presentation of Grave's disease.
AB  - Pruritus is a lesser known symptom of hyperthyroidism, particularly in autoimmune
      thyroid disorders. This is a case report of a 27-year-old woman who presented
      with generalised pruritus at a primary care clinic. Incidental findings of
      tachycardia and a goiter led to the investigations of her thyroid status. The
      thyroid function test revealed elevated serum free T4 and suppressed thyroid
      stimulating hormone levels. The anti-thyroid antibodies were positive. She was
      diagnosed with Graves' disease and treated with carbimazole until her symptoms
      subsided. Graves' disease should be considered as an underlying cause for
      patients presenting with pruritus. A thorough history and complete physical
      examination are crucial in making an accurate diagnosis. Underlying causes must
      be determined before treating the symptoms. 

PMID- 25606264
TI  - Reactive arthritis in tuberculosis: A case of Poncet's disease.
AB  - Reactive arthritis and erythema are uncommon presentations of tuberculosis (TB).
      Reactive arthritis in tuberculosis (TB) is known as Poncet's disease, a rare
      aseptic form of arthritis observed in patients with active TB. We report a case
      of Poncet's disease in a 20-year old man whose reactive arthritis overshadowed
      other clinical symptoms of TB resulting in delayed diagnosis and treatment.
      Although a conclusive diagnosis of Poncet's disease is not possible, reactive
      immunologic reactions such as reactive arthritis and erythema nodosum even
      without respiratory symptoms should raise suspicion on possible TB. Thus, taking
      a thorough medical history as well as performing relevant examinations and
      investigations for possible TB will help expedite the diagnostic process. 

PMID- 25606265
TI  - Hot water immersion as a treatment for stonefish sting: A case report.
AB  - The North Borneo state of Sabah is known worldwide for its beautiful islands and
      dive sites. Local hospitals deal with a number of marine-related injuries,
      including marine fauna envenomation by Scorpaenidae and Synanceiidae families of
      fish. We report a case of a tourist who presented with excruciating pain on her
      right foot after stepping on a stonefish. Despite being given parenteral
      analgesia and regional anaesthesia, the pain persisted. Her pain improved after
      she soaked her foot in hot water for about 30 minutes. No further treatment was
      required. We reviewed the literature comparing this inexpensive mode of treatment
      with other conventional treatments. We also explored the possibility of using hot
      water immersion for treatment of envenomation by other types of marine animals. 

PMID- 25606266
TI  - Sequelae of neglected senile cataract.
AB  - Cataract is the most common cause of blindness in the world. An attack of
      phacolytic and phacomorphic glaucoma as a result of neglected cataract
      constitutes a medical emergency that must be addressed immediately. Ocular
      emergencies such as these is challenging for the surgeon with guarded or poor
      prognosis. We describe the presentation, management and prognosis of three cases
      of phacomorphic and phacolytic glaucoma. All three patients underwent aggressive
      management of intraocular pressure. Despite successful cataract operation with
      implantation of intraocular lens, there was only mild improvement of the vision.
      Optic nerve and pupil functions were permanently affected following the insult.
      Phacomorphic and phacolytic glaucoma present a very challenging problem to the
      surgeon with poor visual outcome. Public health education and awareness are
      important and health workers should encourage patients with cataract to seek
      early treatment for better prognosis. 

PMID- 25606267
TI  - Dangerous diplopia: A case of pansinusitis.
AB  - PURPOSE: To report a case of pansinusitis after swimming in a common pool. CASE
      REPORT: Acute sinusitis is ranked the fifth-most common indication for antibiotic
      prescriptions.2 Although sinusitis is often diagnosed clinically, cases that are
      resistant to conventional antibiotic therapy or recurrent cases may require
      diagnostic imaging in order to confirm the diagnosis. The complications of
      sinusitis, though rare, may lead to serious consequences if not diagnosed and
      treated early. We report a 33-year old man with pansinusitis presenting with a
      sudden onset of peripheral gaze diplopia associated with progressive frontal
      headache. His symptom resolved completely after he was given intravenous
      antibiotics and a nasal decongestant.

PMID- 25606268
TI  - Masked rhinolith: The significance of unilateral symptom.
AB  - This is a case report of an 11-year old child who was suffering from rhinorrhoea
      for five years. As there was no history of foreign body insertion into the nose,
      the diagnosis of a nasal problem was not suspected. Furthermore, the initial
      presentation of unilateral rhinorrhoea (nasal discharge) masked the suspicion of
      other pathologies. The child was treated for allergic rhinitis until she
      presented herself to our attention whereby a rhinoscopy was performed, showing a
      rhinolith. 

PMID- 25606269
TI  - The ' widow maker': Electrocardiogram features that should not be missed.
AB  - Patients with Wellen's syndrome often present with chest pain and found to have
      specific precordial T-wave changes on the electrocardiogram (ECG). They
      subsequently develop a large anterior wall myocardial infarction. These specific
      electrocardiographic abnormalities are associated with critical stenosis of the
      proximal left anterior descending coronary artery (LAD). This syndrome is often
      under-recognised and has fatal consequences; it is, therefore, also known as the
      widow maker. We highlight a case of a 39-year old gentleman who had a history of
      coronary artery disease and typical ECG characteristics of Wellen's syndrome. 

PMID- 25606270
TI  - Scales on the scalp.

PMID- 25606271
TI  - An adult patient with double vision.

PMID- 25606272
TI  - Sudden-onset of hearing loss after a slap.

PMID- 25606273
TI  - Practising EBM in primary care.

PMID- 25606274
TI  - Evidence-based practice in Malaysia: where are we and what more can be done?

PMID- 25606275
TI  - Teaching evidence-based medicine: a clinician's perspective.

PMID- 25606276
TI  - From mummified guidelines to living evidence-based medicine: three essential
      tools.

PMID- 25606277
TI  - A preliminary study of job satisfaction and motivation among the Malaysian
      primary healthcare professionals.
AB  - AIM: This study aimed to examine the relationship between personal or work-based
      characteristics and job satisfaction and motivation in Malaysian primary
      healthcare professionals. METHODS: This was a cross-sectional survey conducted
      during the 15th Family Medicine Scientific Conference in June 2011 using the Warr
      Cook-Wall scales. The questionnaires included demography and work-related items
      and were self-distributed and returned at the end of the conference. Independent
      risk factors were identified using multiple linear regressions. RESULTS: A total
      of 149 conference participants completed the survey, with a response rate of
      33.1%. They were mainly females (85.2%), Malay (83.2%), and married (83.9%) in
      almost equal proportions of practice location (urban 57.8% and rural 42.2%).
      Majority of them were working at community-based health clinics (74.0%) and in
      public sectors (94.4%). The respondents were mainly doctors (91.4%). The mean age
      of the participants was 39.1 years (SD 8.0), with a mean duration of service of 9
      years (SD 6.9). Family medicine specialty (FMSt) residents had lower job
      satisfaction (B = -8.0, 95% CI -14.61 to -1.40, p = 0.02). Family medicine
      specialists (FMSs) had higher satisfaction with working conditions (B = 1.95, 95%
      CI 0.50 to 3.41, p = 0.01). A male worker had on average 2.8 (95% CI -4.7 to 
      0.9, p = 0.005) lower points in the total intrinsic job motivation scale. There
      was a positive relationship between the duration of working and job motivation (B
      = 0.10, 95% CI 0.004 to 0.2, p = 0.04). CONCLUSION: FMSt residents might have the
      least job satisfaction, but FMSs were generally satisfied with their working
      conditions regardless of the location of their clinics. Men and those who were
      novice in primary healthcare may need more support for motivation.

PMID- 25606278
TI  - The effect of profiling report on antibiotic prescription for upper respiratory
      tract infection.
AB  - INTRODUCTION: Upper respiratory tract infection (URTI) is a common encounter in
      primary care and mostly viral in origin. Despite frequent reminders to primary
      care providers on judicious use of antibiotics for URTI, the practice is still
      rampant. METHODS: As part of quality improvement initiative, an intervention was
      designed by distributing a profiling report on individual prescriber's
      performance in comparison to colleagues on usage of antibiotic for URTI. The data
      were generated from electronic health record in three public primary care clinics
      in Malaysia and emailing monthly throughout 2011 to all providers. RESULTS: There
      were 22,328 consultations for URTI in 2010 and 22,756 in 2011 with the incidence
      rates of URTI among overall consultations of 15.7% and 15.9% respectively. 60
      doctors and medical assistants had performed consultations during the 2 year
      period. Following the intervention in 2011, the prescription rate of antibiotic
      for URTI is significantly reduced from 33.5% in 2010 to 23.3 % in 2011. Before
      intervention, individual prescription rate varies from 9.7% to 88.9% and reduced
      to 4.3% to 50.5% after intervention. CONCLUSION: Profiling report is a potential
      method of changing antibiotic prescribing habit among public primary care
      providers in Malaysia especially if the baseline adherence was poor and higher
      variation of prescribing rate.

PMID- 25606279
TI  - Management of otitis media with effusion in children.

PMID- 25606280
TI  - Management of postmenopausal osteoporosis.

PMID- 25606281
TI  - Do calcium supplements increase the risk of cardiovascular events?

PMID- 25606282
TI  - Treatment of acute gout in patients with coronary artery disease.

PMID- 25606283
TI  - A postmenopausal osteoporotic woman losing bone mineral density despite
      bisphosphonates.
AB  - Bisphosphonates are pyrophosphate analogues, with a strong affinity for bones.
      They inhibit bone resorption and are currently the first choice of treatment for
      osteoporosis. Bisphosphonates should be taken in a specific manner and for at
      least one year to be effective in the maintenance and improvement of bone mineral
      density (BMD), as well as for protection against fractures. We report a case of a
      postmenospausal osteoporotic woman who lost BMD despite being on bisphosphonate
      therapy for eight years, highlighting issues that a primary care doctor needs to
      address before deciding on the next best option. 

PMID- 25606284
TI  - Peritonsillar swelling is not always quinsy.
AB  - Quinsy is a common encounter in family physician practice. It is defined as a
      collection of purulent material in the peritonsillar space, giving appearance of
      unilateral palatal bulge. Presenting symptoms include trismus, muffled voice,
      odynophagia, and ipsilateral otalgia. When the diagnostic needle aspiration
      reveals no pus, the diagnosis is changed into peritonsillar cellulitis or also
      known as perintonsillitis. Peritonsillitis is sufficiently treated with
      antibiotics unlike a quinsy which warrants surgical incision and drainage. 

PMID- 25606285
TI  - A child with swelling between the eyes.

PMID- 25606286
TI  - Swyer syndrome in a woman with pure 46, XY gonadal dysgenesis and a hypoplastic
      uterus.
AB  - Swyer syndrome or pure 46, XY gonadal dysgenesis is a condition in which the
      individuals have female appearance. They classically present as sexually
      infantile phenotypic females with primary amenorrhoea. People with this disorder
      have female external genitalia but the uterus and fallopian tubes are
      underdeveloped. However, they do not have functional gonads (ovaries or testes).
      Instead, they have streak gonads. We are reporting a case of Swyer syndrome with
      partially developed breasts, hypoplastic uterus, and absent streak gonads. The
      patient was treated with hormonal therapy and few years after her presentation,
      breast and uterine development were noted. In view that the patient is already
      married, the option of fertility was discussed with her. This case illustrates a
      rare case of gonadal dysgenesis and demonstrates the importance of counseling on
      the options of treatment, especially regarding fertility. 

PMID- 25606287
TI  - A chinese new year rash.

PMID- 25606288
TI  - The child with suspected hearing loss.

PMID- 25606289
TI  - Nurturing tomorrow's family doctors.

PMID- 25606290
TI  - Onychomycosis nailed.
AB  - Fungal infection of the nail is a common condition that causes much concern
      because of its disfiguring appearance. Although specific treatment is available
      for this condition, treatment outcome is variable and persistent nail dystrophy
      post-treatment may cause distress to both the patient and the physician. This
      article describes the current available treatment options for onychomycosis,
      management approach and the expected treatment outcome to enhance primary care
      physicians' confidence in managing this condition. Oral antifungal agents such as
      terbinafine and itraconazole are good treatment options for onychomycosis.
      Combination therapy using oral antifungal agents with topical lacquer
      preparations may provide added benefits. Evaluation of patient's expectations,
      providing information on treatment outcome, clinical cure and recurrence rates
      are essential in the management of onychomycosis. This article is intended to
      guide primary care physicians to achieve realistic treatment goals and for a
      satisfactory experience in the overall management of this challenging condition. 

PMID- 25606291
TI  - Involvement of practice nurses and allied health professionals in the development
      and management of care planning processes for patients with chronic disease - A
      pilot study.
AB  - INTRODUCTION: Medicare items were introduced in 2005 to encourage general
      practitioners (GPs) to involve other healthcare providers in the management of
      patients with chronic disease. However, there appears to be barriers to
      converting financial incentives and the use of information technology as a
      communication tool to better patient outcomes. The aim of this study was to
      explore these barriers from the perspectives of practice nurses and allied health
      practitioners. METHODS: Three focus groups were held, comprising a convenience
      sample of 10 practice nurses and 17 allied health professionals from south-east
      Melbourne. FINDINGS: FINDINGS were reported under five themes: (1) attitudes and
      beliefs, (2) communication using care planning documents, (3) electronic
      communication, (4) care planning and collaboration between healthcare
      professionals and (5) ongoing challenges. CONCLUSION: While allied professionals
      use care planning tools, there is confusion about the extent to which these tools
      are for the GPs to provide structured care to assist with communication or
      funding mechanisms for allied health services. Further research is needed on the
      contributions of these groups to the care planning process and how communication
      and collaboration between healthcare professionals can be strengthened.

PMID- 25606292
TI  - Malaysian Clinical Practice Guideline for the Management of Psoriasis Vulgaris:
      Summary of recommendations for management in primary healthcare setting.

PMID- 25606293
TI  - The experience of managing a retroviral antenatal patient in a primary care
      clinic in Perak, Malaysia.

PMID- 25606294
TI  - Hoarseness as the sole symptom of an impending thoracic aneurysm rupture?
AB  - Unilateral vocal cord palsy secondary to thoracic aortic aneurysm is a rare
      occurrence. Direct compression of the enlarging thoracic aneurysm on the left
      recurrent laryngeal nerve causes neuronal injury of the nerve, which is
      manifested as hoarseness. We present a rare case of unilateral vocal cord palsy
      in a 60-year-old healthy gentleman caused by a large thoracic aortic aneurysm.
      This rare presentation, with a serious underlying pathology might be misdiagnosed
      or delayed. Therefore, it is important for us to have high index of suspicion in
      cases with a rare presentation such as this. 

PMID- 25606295
TI  - Otitis externa complicated with chloramphenicol ear drops-induced perichondritis.
AB  - Otitis externa is a common condition of the ear. It is manifested as narrowing of
      the lumen owing to the edematous swelling of the ear canal lining. Perichondritis
      may occur independently or as a complication of the otitis externa. We report a
      case of perichondritis after using a topical ear drop. Changing the medication
      provides immediate resolution of the condition. 

PMID- 25606296
TI  - Rhinolith: An important cause of foul-smelling nasal discharge.
AB  - Rhinoliths result from neglected nasal foreign bodies that gradually increase in
      size. They are usually discovered incidentally during routine ENT examination or
      due to the associated symptoms such as nasal obstruction or persistent foul
      smelling unilateral nasal discharge. A case of a 14-year-old girl was reported
      with a year history of the symptom. The foul-smelling nasal discharge noted by
      her mother was not the main concern to them. She was referred by her primary care
      physician as she complained of impacted ear wax. However, rhinolith was
      incidentally found upon routine clinical examination in the ENT clinic and was
      removed uneventfully. 

PMID- 25606297
TI  - A Rejang River rash.

PMID- 25606298
TI  - A pulsating mass in the pre-auricular region.

PMID- 25606299
TI  - A joint estimation detection of Glaucoma progression in 3D spectral domain
      optical coherence tomography optic nerve head images.
AB  - Glaucoma is an ocular disease characterized by distinctive changes in the optic
      nerve head (ONH) and visual field. Glaucoma can strike without symptoms and
      causes blindness if it remains without treatment. Therefore, early disease
      detection is important so that treatment can be initiated and blindness
      prevented. In this context, important advances in technology for non-invasive
      imaging of the eye have been made providing quantitative tools to measure
      structural changes in ONH topography, an essential element for glaucoma detection
      and monitoring. 3D spectral domain optical coherence tomography (SD-OCT), an
      optical imaging technique, has been commonly used to discriminate glaucomatous
      from healthy subjects. In this paper, we present a new framework for detection of
      glaucoma progression using 3D SD-OCT images. In contrast to previous works that
      the retinal nerve fiber layer (RNFL) thickness measurement provided by
      commercially available spectral-domain optical coherence tomograph, we consider
      the whole 3D volume for change detection. To integrate a priori knowledge and in
      particular the spatial voxel dependency in the change detection map, we propose
      the use of the Markov Random Field to handle a such dependency. To accommodate
      the presence of false positive detection, the estimated change detection map is
      then used to classify a 3D SDOCT image into the "non-progressing" and
      "progressing" glaucoma classes, based on a fuzzy logic classifier. We compared
      the diagnostic performance of the proposed framework to existing methods of
      progression detection.

PMID- 25606300
TI  - Effectiveness of lasers in the treatment of dentin hypersensitivity.
AB  - Dentin hypersensitivity (DH) is a relatively common painful condition among
      dental problems. Although many studies have been performed regarding the
      diagnosis and treatment of DH, dental practitioners are still confused about the
      definite diagnosis and treatment.The use of lasers as a treatment for dentin
      hypersensitivity was first introduced in 1985.Laser treatment in dentin
      hypersensitivity is an interesting and controversial issue and many
      investigations have been done on its mechanism of action, advantages, and unclear
      points.The present literature review tries to go over the definition, diagnosis,
      etiology , predisposing factors, various laser types in the treatment of DH alone
      or in combination with topical desensitizing agents. Since a certain treatment
      has not yet introduced for dentin hypersensitivity, a combination of laser
      therapy and topical desensitizing factors ,can increase the success of the
      treatment compared with either treatments alone. 

PMID- 25606301
TI  - Disinfection of Contaminated Canals by Different Laser Wavelengths, while
      Performing Root Canal Therapy.
AB  - Removal of smear layer and disinfection of canals are important objectives of
      teeth root canal cleaning. In order to achieve this purpose, rinsing substances,
      intra canal drugs as well as ultrasound are used. Today, use of laser to remove
      smear layer and to disinfect root canals has increasingly attracted the
      attentions. Till now different lasers such as CO2, Nd:YAG, Er:YAG, Er,Cr:YSGG
      have been used for debris and smear removal from the canals. Numerous studies
      have shown that Er:YAG is the most appropriate laser for intra canal debris and
      smear removal. In addition different laser wavelengths have been used directly or
      as an adjunctive to disinfect canals. Laser light can penetrate areas of canals
      where irrigating and disinfecting solutions cannot reach, like secondary canals
      and deep dentinal tubules and also can eliminate microorganisms. Different
      studies have confirmed the penetration of Nd:YAG laser in deep dentin and
      reduction of microorganisms penetration. But studies on comparison of
      antibacterial effects of Nd:YAG laser with sodium hypochlorite showed
      effectiveness of both, with a better effect for sodium hypochlorite. Studies
      performed in relation with anti-microbial effects of Diode laser with various
      parameters show that this laser can be effective in reducing intra canal
      bacterial count and penetration in the depth of 500 microns in dentin. In studies
      performed on Diode laser in combination with canal irrigating solutions such as
      sodium hypochlorite and oxygenated water better results were obtained. Although
      studies on disinfection by the Erbium laser family show that use of this laser
      alone can be effective in disinfecting canals, studies evaluating the
      disinfecting effects of this laser and different concentrations of sodium
      hypochlorite show that the latter alone is more effective in disinfecting canals.
      And better results were obtained when Erbium laser was used in combination with
      sodium hypochlorite irrigating solution in canals. Results of the aforementioned
      articles indicate that this laser is effective in combination with a rinsing
      solution such as sodium hypochlorite. Results from studies including several
      types of the different Er:YAG, Ho:YAG, Nd:YAG, Er,Cr:YSGG lasers in disinfecting
      canals showed that all wavelengths used in disinfection for different thicknesses
      of dentin were efficacious without damaging thermal effect. Considering that use
      of different lasers in canals can be accompanied with temperature increase which
      can sometimes lead to damages to teeth and surrounding tissues, thus the use of
      photochemical phenomenon for elimination of microorganisms have attracted
      attention of many researchers. Studies in this field imply the efficacy of this
      method in reducing canal bacterial count and recommend its use as an adjunctive
      after biomechanical preparation of canals. Results from performed studies show
      removal of intra canal debris and smear layer by different lasers and
      particularly the Erbium laser family. Furthermore various laser wavelengths,
      particularly of Diode and Nd:YAG lasers can be effective in reducing intra canal
      microbial count. Maximum effect is obtained when laser light is used in canals in
      combination with sodium hypochlorite irrigating substance in appropriate
      concentration. Therefore use of laser energy can improve success rate of root
      canal treatments. 

PMID- 25606302
TI  - The Effect of Light Therapy on Superficial Radial Nerve Conduction Using a
      Clustered Array of Infrared Super luminous Diodes and Red Light Emitting Diodes.
AB  - INTRODUCTION: Lasers, light emitting diodes (LEDs) and super luminous diodes
      (SLDs) are widely used to treat selected musculoskeletal, integumentary and
      neurological conditions.The mechanisms underlying the reported treatment effects
      of light therapy are unclear and the physiologic effect of light on a variety of
      tissues, particularly neurological, is mostly unknown. A few researchers have
      reported on the effects of lasers and to a lesser extent infrared LEDs on nerve
      conduction in superficial nerves, but there is little evidence of the effects of
      SLDs and red LEDs on conduction parameters of peripheral nerves. The purpose of
      this study was to examine the effects of a light therapy generated by cluste
      rprobe containing an array of infrared super luminous and red light emitting
      diodes on superficial radial nerve conduction. METHODS: This was a single blind,
      randomized controlled trial conducted in an academic clinical laboratory. Thirty
      two healthy participants (mean age = 25 years) were randomized to a treatment
      group or a placebo group. The treatment group received light irradiation through
      the application of a cluster probe containing 32 infrared (880nm) SLDs and 4 red
      (660nm) LEDs for 30 seconds at a dose of 6 J/cm(2) to each of the two 5 cm(2)
      segments of skin overlying the superficial radial nerve. The placebo group
      received identical set-up without the application of light irradiation. Negative
      peak latency (NPL) and conduction velocity (NCV) for the superficial radial nerve
      were measured before treatment and for 10-minutes following treatment at 2-minute
      intervals. Skin temperature was monitored throughout. RESULTS: No significant
      differences between groups and over time for NPL, NCV, or temperature difference
      scores were identified. However, a significant increase in skin temperature was
      measured over time at each time point compared to baseline. CONCLUSION: Light
      irradiation using a cluster probe containing infrared super luminous and red
      light emitting diodes does not impact the neurophysiological properties of the
      superficial radial nerve.

PMID- 25606303
TI  - Implant Bed Preparation with an Erbium, Chromium Doped Yttrium Scandium Gallium
      Garnet (Er,Cr: YSGG) Laser Using Stereolithographic Surgical Guide.
AB  - BACKGROUND: Implant bed preparation with laser is taken into consideration owing
      to the increased interest in use of lasers in hard tissue surgery. The purpose of
      this study is to determine the deviations in the position and inclination between
      the planned and prepared implant beds with Erbium, Chromium doped Yttrium
      Scandium Gallium Garnet (Er,Cr:YSGG) laser using stereolithographic (SLA)
      surgical guides. METHODS: After 3-dimensional (3D) imaging of six sheep lower
      jaws, computed tomography (CT) images were transformed into 3D models. Locations
      of implant beds were determined on these models. Two implant beds in each half
      jaw were prepared with an Er,Cr:YSGG laser system and a conventional drilling
      method using a total of 12 SLA surgical guides. A new CT was taken to analyze the
      deviation values between planned and prepared implant beds. Finally, a software
      program was used to superimpose the images on 3D models, then the laser and
      conventional drilling groups were compared. RESULTS: Differences of mean angular
      deviations between the planned and prepared implant beds were 5.17+/-4.91 degrees
      in the laser group and 2.02+/-1.94 degrees  in the conventional drilling
      group.The mean coronal deviation values were found to be 0.48+/-0.25 mm and
      0.23+/-0.14 mm in the laser group and conventional drilling group, respectively.
      While the mean deviation at the apex between the planned and prepared implant
      beds were 0.70+/-0.26 mm and 0.26+/-0.08 ,the mean vertical deviations were
      0.06+/-0.15 mm and 0.02+/-0.05 mm for the laser group and the conventional
      drilling group, respectively. CONCLUSION: It is possible to prepare an implant
      bed properly with the aid of Er,Cr:YSGGlaser by using SLA surgical guide.

PMID- 25606304
TI  - Solar Lentigines: Evaluating Pulsed Dye Laser (PDL) as an Effective Treatment
      Option.
AB  - INTRODUCTION: Solar lentigines are among commonest cosmetic problems. There are
      many topical therapies suggested to treat these lesions including cryotherapy,
      chemical peeling with tri chloro acetic acid (TCA) and laser therapy with q
      switched lasers as well as long pulsed lasers. Considering possible treatment
      side effects (PIH, scar) with cryotherapy and peeling in Iranian patients (darker
      skin types) it seems necessary to try to find alternative measures. The aim of
      the present study was to evaluate effect of long pulsed dye laser (LPDL) on
      lentigines via an objective method (computerized dermoscopy). METHODS: Patients
      with pathologically confirmed lentigines were selected if they agreed to
      participate in the study,were not treated before, hadn't history of psoriasis,
      vitiligo, scar formation and were not pregnant. Letigines were dermoscopied
      before and after treatment with PDL (V-beam, 595nm, Candela Corp. Wayland, USA)
      using fluence of 10 joules,without DCD (dynamic cooling device) via extra
      compress lens provided with laser system.The resulting figures were compared by
      two academic unrelated dermatologists as well as by computerized analysis. Post
      laser side effects were treated with topical antibiotics and mild topical
      steroids. Patients were followed for six months after the end of the study to
      determine the rate of recurrence via dermoscopy of sites of previous lesions and
      also delayed side effects. RESULTS: A total of 21 patients with the same number
      of lesions, were included in the study.Mean age of patients was 54.2 years (+/
      23.3) ranging from 39 to 71 years. Included patient swere 18 females and three
      males. From 21 treated lesions, 11 were located on the hands and 10 on the face.
      Comparing before and after photographs taken through dermoscopy system,revealed
      that approximately 57% of patients had more than 75% improvement. Mean pigment
      analysis score (calculated by computerized dermoscope software) was respectively
      8 and 2 before and after PDL therapy, showing noticeable decrease in pigment
      density of lesions.Side effects were mild erythema and local irritation
      responding to topical mild steroids.No hypo or persistent hyper pigmentation or
      other delayed side effects was seen after six months follow up. One patient
      experienced transient hyper pigmentation of treatment site after treatment.
      During six months follow up, no recurrences were seen. CONCLUSION: In conclusion,
      PDL is a safe and effective option to treat lentigines if applied properly using
      compression method, especially in Iranian patients. However, further studies with
      larger sample size are required to confirm these results.

PMID- 25606305
TI  - Assessment of Microleakage of Class V Composite Resin Restoration Following
      Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) Laser Conditioning and Acid Etching
      with Two Different Bonding Systems.
AB  - INTRODUCTION: The use of laser for cavity preparation or conditioning of dentin
      and enamelsurfaces as an alternative for dental tissue acid-etch have increased
      in recent years. Theaim of this in vitro study was to compare microleakage at
      enamel-composite and dentincompositeinterfaces following Erbium-Doped Yttrium
      Aluminum Garnet(Er:YAG) laserconditioning or acid-etching of enamel and dentin,
      hybridized with different bonding systems. METHODS: Class V cavities were
      prepared on the lingual and buccal surfaces of 50 recentlyextracted intact human
      posterior teeth with occlusal margin in the enamel and gingival marginin the
      dentin. The cavities were randomly assigned to five groups: group1:conditioned
      withlaser (Energy=120mJ, Frequency=10Hz, Pulse duration=100MUs for Enamel and
      Energy=80mJ,Frequency=10Hz, Pulse duration=100MUs for Dentin) + Optibond FL,
      group2:conditioned withlaser + etching with 35% phosphoric acid + Optibond FL,
      group3:conditioned with laser+ Clearfil SE Bond, group 4 (control):acid etched
      with 35% phosphoric acid + OptibondFL, group 5 (control): Clearfil SE Bond. All
      cavities were restored using Point 4 compositeresin. All samples were stored in
      distilled water at 37 degrees c for 24 h, then were thermocycled for500 cycles
      and immersed in 50% silver nitrate solution for 24 h. The teeth were
      sectionedbucco-lingually to evaluate the dye penetration. Kruskal-Wallis & Mann
      Whitney testswere used for statistical analysis. RESULTS: In occlusal margins,
      the least microleakage showed in groups 2, 4 and 5. Themaximum microleakage was
      observed in group 3 (P=0.009). In gingival margins, the leastmicroleakage was
      recorded in group2, while the most microleakage was found in group5 (P=0.001).
      Differences between 5 study groups were statistically significant (P<0.05).The
      microleakage scores were higher at the gingival margins. CONCLUSION: The use of
      the Er:YAG laser for conditioning with different dentin adhesivesystems
      influenced the marginal sealing of composite resin restorations.

PMID- 25606306
TI  - Morphological Changes of Human Dentin after Erbium-Doped Yttrium Aluminum Garnet
      (Er:YAG) and Carbon Dioxide (CO2) Laser Irradiation and Acid-etch Technique: An
      Scanning Electron Microscopic (SEM) Evaluation.
AB  - INTRODUCTION: The aim of this study was to investigate the morphological changes
      of human dentin after Erbium-Doped Yttrium Aluminum Garnet (Er:YAG), Carbon
      Dioxide(CO2) laser-irradiation and acid-etching by means of scanning electron
      microscopic (SEM) Methods: 9 extracted human third molars were used in this
      study. The teeth were divided in three groups: first group, CO2 laser with power
      of 1.5 w and frequency of 80 Hz; second group, Er:YAG laser with output power of
      1.5 W frequency of 10 Hz, very short pulse with water and air spray was applied;
      and third group, samples were prepared by acid-etching 37% for 15 sec and rinsed
      with air-water spray for 20 sec. Then, the samples were prepared for SEM
      examination. RESULTS: Melting and cracks can be observed in CO2 laser but in
      Er:YAG laser cleanedablated surfaces and exposed dentinal tubules, without smear
      layer was seen. CONCLUSION: It can be concluded that Er:YAG laser can be an
      alternative technique for surface treatment and can be considered as safe as the
      conventional methods. But CO2 laser has some thermal side effects which make this
      device unsuitable for this purpose.

PMID- 25606307
TI  - Treatment of Ankyloglossia with Carbon Dioxide (CO2) Laser in a Pediatric
      Patient.
AB  - INTRODUCTION: Laser surgery as an alternative for conventional surgical procedure
      has gained special attention. Using Carbon Dioxide (CO2) laser has some benefits
      like less post-operative pain, swelling and infection, decrease in risk of
      metastasis and edema, and less bleeding providing dry sites for surgery. CASE
      REPORT: A 12 years old boy with lingual frenum with indication for excision was
      referred to the laser department of Tehran University of medical sciences dental
      school.CO2 laser was used with 10600 nm wavelength, 1.5 W output power, 100 Hz
      frequency and 400 MUsec pulse duration in non-contact mode. RESULTS: The result
      of using CO2 laser was dry and bloodless field during operation, no post
      operative swelling, no pain or discomfort, with normal healing process.
      CONCLUSION: We suggest and stimulate the use of CO2 laser for soft tissue surgery
      because of elimination of suture, convenient coagulation, time saving, patients'
      comfort and easy manipulation.

PMID- 25606308
TI  - Application of Low level Lasers in Dentistry (Endodontic).
AB  - Low level lasers, cold or soft lasers: These lasers do not produce thermal
      effects on tissues and induce photoreactions in cells through light stimulation
      which is called photobiostimulation. Power of these lasers is usually under
      250mW. The main point differentiating low level lasers and high power ones is the
      activation of photochemical reactions without heat formation. The most important
      factor to achieve this light characteristic in lasers is not their power, but
      their power density for each surfa ceunit (i.e cm(2)). Density lower than
      670mW/cm(2), can induce the stimulatory effects of low level lasers without
      thermal effects. Low level lasers (therapeutic) used today as treatment
      adjunctive devices in medicine and dentistry. Numerous studies have been
      performed on the applications of low level lasers in patient pain reduction.
      Mechanisms of pain reduction with therapeutic lasers and their application are
      expressed, and the studies realized in this field are presented. 

PMID- 25606309
TI  - Low level laser therapy for painful joints.
AB  - Low Level Laser Therapy (LLLT) uses a light source that generates extremely pure
      light, of a single wavelength(1). The effect is not thermal, but rather related
      to photochemical reactions in the cells. LLLT was introduced as an alternative
      non-invasive treatment for OA about 10 years ago, but its effectiveness is still
      controversial(2). A Cochrane review of LLLT in osteoarthritis included five
      trials, and concluded that despite some positive findings, the meta-analysis
      lacked data on how LLLT effectiveness was affected by the important factors of
      wavelength, treatment duration of LLLT, dosage, and site of application over
      nerves instead of joints(1,3,4,5,6,7). A different review(2) addresses some of
      these issues in a wider range of trials, and is broadly positive, if limited by
      numbers. 

PMID- 25606310
TI  - The 808 nm Laser-Assisted Surgery as an Adjunct to Orthodontic Treatment of
      Delayed Tooth Eruption.
AB  - INTRODUCTION: Failure of teeth to erupt from gingival tissues at usual
      developmental time is called delayed tooth eruption (DTE). Delayed tooth eruption
      lead to prolonged fixed orthodontic treatment and its eventual complications. The
      purpose of the present study was to evaluate the effect of laser-assisted (808
      nm) surgical uncovering, on the tooth emergence and orthodontic treatment of DTE.
      METHODS: A total of 16 orthodontic patients were included in this study and were
      equally assigned to an experimental and a control group. Subjects for experiment
      consisted of eight patients (6 girls and 2 boys) with a mean age of 14+/-0.9
      years. All patients exhibited delayed second premolar eruption. The laser
      wavelength was 810 nm and it was set in a continuous wave mode at a power output
      of 1.6 watt with a 0.3-mm diameter fiber tip. When the target tissue was
      sufficiently anesthetized, the tip was directed at an angle of 10 to 20 degrees
      to the tissue (light contact mode); and was applied continuously for
      approximately 12 Seconds until an acceptable tooth exposure area was visible. The
      facial axis of the clinical crown (FACC) line represents the most prominent
      portion of the facial central lobe for premolars. All orthodontic brackets are
      aligned along this reference and are located on FA (Facial Axis) point. The
      standard for adequate tooth eruption was the accessibility of facial axis of the
      clinical crown (FACC) for bonding the brackets. Data gathered from the patients
      were statistically surveyed and compared by means of Tukey's Test and Analysis of
      Variance (ANOVA). RESULTS: All patients showed good gingival status, no
      significant bleeding during or immediately after the surgery, and acceptable
      level of healing after laser surgery. The biologic width of the teeth was
      preserved and no violation of this important periodontal parameter was observed.
      The average time for accessing the FA point in experimental group was 11+/-1.1
      weeks and the mentioned period was increased to 25+/-1.8 weeks in control group.
      The data analysis showed that in patients with DTE, laser intervention
      significantly accelerated tooth eruption (P < 0.05). CONCLUSION: Laser-assisted
      surgical removal of the fibrous tissue over erupting premolars (DTE) with
      appropriate irradiation parameters appears to be a promising adjunct to
      orthodontic treatment for bringing the premolar to the aligned and leveled dental
      arch.

PMID- 25606311
TI  - Scanning Electron Microscope Comparative Evaluation of Feldspathic Porcelain
      Surfaces under Irradiation by Different Powers of Neodymium-Doped Yttrium
      Aluminium Garnet (Nd:YAG) Laser.
AB  - INTRODUCTION: Recent use of lasers for porcelain surface treatment for adhesion
      of brackets to restorations has not only showed some promising results, but is
      also accompanied with less undesirable effects among other advantages. The
      purpose of this study is the comparative electron microscope evaluation of
      feldspathic porcelain surfaces under irradiation by Neodymium-Doped Yttrium
      Aluminium Garnet (Nd:YAG) with different powers (0.75, 1.5 and 2W) via the acid
      etching with hydrofluoric acid (HF) technique. METHODS: The glazed porcelain
      samples were obtained by duplicating labial surfaces of maxillary central incisor
      teeth. The specimens were randomly treated by 4 different methods. Group1 was
      etched with hydrofluoric acid 9.6%. Samples in group 2 to 4 were also irradiated
      by Nd:YAG laser with different powers: 0.75, 1.5 and 2W. Then the samples were
      prepared for evaluation by scanning electron microscope (SEM). RESULTS: Etching
      quality from a porosity point of view was similar for group2 and HF group. Laser
      with power of 0.75W has little potential to create mechanical porosity.
      CONCLUSION: In regard of the results of this study, it is possible to benefit
      from Nd:YAG laser with appropriate parameters for surface conditioning.

PMID- 25606312
TI  - Effect of low level laser application at the end of surgery to reduce pain after
      tonsillectomy in adults.
AB  - INTRODUCTION: Tonsillectomy is among commonest otorhinolaryngologic surgeries.
      Many methods have been used to control post surgical pain, but despite it, pain
      is still one of the problems related to this operation. Recently, due to the non
      invasiveness of low level lasers, this modality has attracted attention. The
      purpose of this study is to evaluate the effects of low level laser irradiation
      at the end of surgery on reduction of pain after tonsillectomy in adults.
      METHODS: In a clinical trial, 60 adult patients, candidates for tonsillectomy
      were randomly assigned to two groups, A and B, and both groups were anesthetized
      similarly by the same technique. At the end of surgery, in the case group, the
      tonsils' bed were irradiated by infrared laser with 980nm wavelength, 100Hz,
      4J/cm(2) from the infra mandibular angle. In the control group, the tonsils' bed
      had laser therapy with a turned off probe. Following laser treatment, the
      patients were reversed and extubated and consciousness achieved, pain and
      odynophagia were assessed at 2, 4, 6, 8, 12 and 24h post surgery based on visual
      analog scale for pain (VAS) and analgesic consumption. RESULTS: In the laser
      group frequency of patients with pain sensation in each evaluated hour was lower
      than in the control group. The amount of pain decrease and analgesic consumption
      reduction was significantly higher in patients who received laser (P=0.01).
      CONCLUSION: Based on the results of this study, use of low level lasers is
      effective in reducing tonsillectomy post surgical pain in adults.

PMID- 25606313
TI  - The Effect of Carbon Dioxide (CO2) Laser on Sandblasting with Large Grit and Acid
      Etching (SLA) Surface.
AB  - INTRODUCTION: The purpose of this study was to investigate the effect of 6W power
      Carbon Dioxide Laser (CO2) on the biologic compatibility of the Sandblasting with
      large grit and acid etching (SLA) titanium discs through studying of the Sarcoma
      Osteogenic (SaOS-2) human osteoblast-like cells viability. METHODS: Sterilized
      titanium discs were used together with SaOS-2 human osteoblast-like cells. 6
      sterilized SLA titanium discs of the experimental group were exposed to
      irradiation by CO2 laser with a power of 6W and 10.600nm wavelength, at fixed
      frequency of 80Hz during 45 seconds in both pulse and non-contact settings. SaOS
      2 human osteoblast-like cells were incubated under 37 degrees C in humid
      atmosphere (95% weather, 5% CO2) for 72 hours. MTT test was performed to measure
      the ratio level of cellular proliferation. RESULTS: The results indicated that at
      570nm wavelength, the 6W CO2 laser power have not affected the cellular
      viability. CONCLUSION: CO2 laser in 6w power has had no effect on the biologic
      compatibility of the SLA titanium surface.

PMID- 25606314
TI  - Effect of Laser Treatment on Surface Morphology of Indirect Composite Resin:
      Scanning Electron Microscope (SEM) Evaluation.
AB  - INTRODUCTION: The aim of this study was to evaluate and compare the Scanning
      electron microscope (SEM) of indirect composite conditioned by Erbium-Doped
      Yttrium Aluminum Garnet (Er:YAG) laser, Neodymium-Doped Yttrium Aluminium Garnet
      (Nd:YAG) laser and Carbon Dioxide (CO2) laser. METHODS: 18 indirect composite
      blocks (GC Gradia DA2, Japan) with 15 * 10 * 10 mm dimensions were made. The
      bonding surface of these blocks were polished, then the samples were divided into
      six groups as follow: Er:YAG laser with output power of 0.5 W and frequency of 10
      Hz, Nd:YAG laser with output power of 0.25, 0.5 W and frequency of 10 Hz, CO2
      laser with output power of 0.5 W and frequency of 10 Hz and 5 Hz, and no
      treatment. Then, the surfaces were evaluated by SEM. RESULTS: Irregularities were
      observed in Er:YAG laser samples compared to control group that produced suitable
      retention for adhesion of cements. Nd:YAG and CO2 lasers showed melting areas.
      CONCLUSION: Among different lasers, Er:YAG laser can be used as an alternative
      technique for surface treatment of indirect composites.

PMID- 25606315
TI  - Clinical application of 810nm diode laser to remove gingival hyperplasic lesion.
AB  - INTRODUCTION: Several treatment options have been introduced for removal of
      gingival hyperplasic lesions, but using diode lasers have many advantages such as
      less bleeding, time saving, better shaping, improved healing and less
      complication for the patients. CASE: A 15-year-old girl with multiple fibroma
      like lesions in the oral cavity, who had a medical history of tuberous sclerosis,
      was selected for gingivoplasty treatment with 810nm diode laser. RESULT: A
      perfect shaping was obtained after removal of the whole lesion in one session and
      no recurrence was observed in 6 months. CONCLUSION: Using laser in the treatment
      of oral lesions leads to excellent wound healing along with excellent functional
      results.

PMID- 25606316
TI  - Mechanisms of Laser-Tissue Interaction: II. Tissue Thermal Properties.
AB  - Laser-tissue interaction is of great interest due to its significant application
      in biomedical optics in both diagnostic and treatment purposes. Major aspects of
      the laser-tissue interaction which has to be considered in biomedical studies are
      the thermal properties of the tissue and the thermal changes caused by the
      interaction of light and tissue. In this review paper the effects of light on the
      tissue at different temperatures are discussed. Then, due to the noticeable
      importance of studying the heat transfer quantitatively, the equations governing
      this phenomenon are presented. Finally a method of medical diagnosis called
      thermography and some of its applications are explained. 

PMID- 25606317
TI  - Laser application in prevention of demineralization in orthodontic treatment.
AB  - One common negative side effect of orthodontic treatment with fixed appliances is
      the development of incipient caries lesions around brackets, particularly in
      patients with poor oral hygiene. Different methods have been used to prevent
      demineralization such as fluoride therapy and application of sealant to prevent
      caries. The recent effort to improve the resistance against the demineralization
      is by the application of different types of lasers. The purpose of this review
      article is discussing the effects of laser in prevention of demineralization in
      orthodontic patients. 

PMID- 25606318
TI  - In Vitro Study of Dentin Hypersensitivity Treated by 980-nm Diode Laser.
AB  - INTRODUCTION: To investigate the ultrastructural changes of dentin irradiated
      with 980-nm diode laser under different parameters and to observe the
      morphological alterations of odontoblasts and pulp tissue to determine the safety
      parameters of 980-nm diode laser in the treatment of dentin hypersensitivity
      (DH). METHODS: Twenty extracted human third molars were selected to prepare
      dentin discs. Each dentin disc was divided into four areas and was irradiated by
      980-nm diode laser under different parameters: Group A: control group, 0 J/cm(2);
      Group B: 2 W/CW (continuous mode), 166 J/cm(2); Group C: 3W/CW, 250 J/cm(2); and
      Group D: 4W/CW, 333 J/cm(2). Ten additional extracted human third molars were
      selected to prepare dentin discs. Each dentin disc was divided into two areas and
      was irradiated by 980-nm diode laser: Group E: control group, 0 J/cm(2); and
      Group F: 2.0 W/CW, 166 J/cm(2). The morphological alterations of the dentin
      surfaces and odontoblasts were examined with scanning electron microscopy (SEM),
      and the morphological alterations of the dental pulp tissue irradiated by laser
      were observed with an upright microscope. RESULTS: The study demonstrated that
      dentinal tubules can be entirely blocked after irradiation by 980-nm diode laser,
      regardless of the parameter setting. Diode laser with settings of 2.0 W and 980
      nm sealed exposed dentin tubules effectively, and no significant morphological
      alterations of the pulp and odontoblasts were observed after irradiation.
      CONCLUSIONS: Irradiation with 980-nm diode laser could be effective for routine
      clinical treatment of DH, and 2.0W/CW (166 J/cm(2)) was a suitable energy
      parameter due to its rapid sealing of the exposed dentin tubules and its safety
      to the odontoblasts and pulp tissue.

PMID- 25606319
TI  - Assessing Health-Related Quality of Life with Antimicrobial Photodynamic Therapy
      (APDT) and Low Level Laser Therapy (LLLT) after Third Molar Removal.
AB  - INTRODUCTION: The purpose of this study was to evaluate the antimicrobial
      photodynamic therapy (APDT) and low level laser therapy (LLLT) on wound healing,
      pain intensity, swelling problems, halitosis and the postoperative usage of
      analgesics after surgical removal of lower third molars. METHODS: One hundred and
      fifty patients, randomly divided into three groups were selected (50 per each
      group). The P1 group received the APDT after a third molar surgery, the P2 group
      received the LLLT and the C group (control group) was without any additional
      therapy after surgery. A photoactive substance was applied in the APDT study
      group before suturing. After 60 seconds the photosensitive substance was
      thoroughly washed with saline water and the laser light was applied in two
      intervals (30 seconds each). The irradiation power was 50 mW while the wavelength
      was 660 nm. The laser therapy in P2 group was performed before suturing and the
      laser light was applied also in two intervals (90 seconds each), the irradiation
      power was 90 mW while the wavelength was the same as in the first group - 660 nm.
      Postoperative follow-ups were scheduled on the third and the seventh day in
      patients who received laser therapy. RESULTS: The results of the postoperative
      evaluation showed that there was a statistically significant difference in the
      postoperative wound healing, pain intensity, swelling problems, halitosis and
      analgesics intake between patients in all three groups (p<0.001). The patients
      that were subjected to APDT (P1) had the least postoperative problems. After the
      laser therapy (P1 and P2) wound healing was without any complications, opposite
      from the patients from the C group (p<0.001). Postoperative application of a
      laser therapy significantly reduced patient's use of analgesics over the observed
      period of time (p<0.001). CONCLUSION: Both modalities of laser therapy
      significantly reduced postoperative problems after surgical removal of third
      lower molars with the best results in both laser groups.

PMID- 25606320
TI  - Effect of Air Abrasion and Erbium-Doped Yttrium Aluminum Garnet (Er: YAG) laser
      preparation on Shear Bond Strength of Composite to Dentin.
AB  - INTRODUCTION: The aim of this study was to assess shear bond strength of
      composite to dentin after air abrasion and laser treatment. METHODS: 40 human
      extracted molars divided into 4 groups (n=10) received the following treatments.
      Group 1: carbide bur, Group 2: air abrasion with aluminum oxide 50 MUm, Group 3:
      irradiated with Erbium-Doped Yttrium Aluminum Garnet (Er: YAG) laser (150
      mJ/20Hz), Group 4: irradiated with Er:YAG laser (150 mJ/20Hz)+ air. Specimens in
      all groups were chemically etched with phosphoric acid 37% and treated with
      bonding agent (single bond 3M). Then, composite build-up was performed by tygon
      tube. After storage in distilled water at 37 degrees c for one week, all
      specimens were subjected to a shear bond strength test with universal testing
      machine. Data were analyzed with ANOVA and T-Test. RESULTS: The mean and standard
      deviation of shear bond strength of the 4 groups were 20.8+/-6.76, 14.98+/-3.98,
      11.43+/-4.36 and 14.95+/- 3.18 MPa, respectively. CONCLUSION: Air abrasion after
      laser treatment improved the shear bond strength.

PMID- 25606321
TI  - Photothrombosis of corneal neovascularization by photodynamic therapy utilizing
      verteporfin and diode laser.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effect of
      photodynamic therapy in the treatment of experimental corneal neovascularization
      (NV) with benzoporphyrin derivative (BPD). METHODS: One group was considered as
      control (n=6 eyes) then, corneal NV was induced in 30 New Zealand male rabbits
      (n=60 eyes) by placing 7.0 silk sutures at midstromal depth approximately1mm from
      the limbus. Fifteen rabbits with corneal NV were left without any treatment, and
      15 rabbits were subjected to photodynamic therapy (PDT) by intravenous injection
      with Verteporfin at a dose of 1.5 mg /Kg. Diode laser (660 nm) was applied after
      15 minutes for 5 minutes with a power of 50 mW/cm2. All rabbits were successively
      followed up by slit lamp examination for periods of 1 day, 1, 2, 3 and 4 weeks.
      Three rabbits were selected and sacrificed weekly (n=6 eyes each) and the corneas
      were isolated for histopathological examination. RESULTS: The results of slit
      lamp examination indicated the gradual regression of the cornea
      neovascularization 4 weeks of PDT. Furthermore, regression of corneal
      neovascularization was documented clinically by decrease number and length of
      blood vessels and by histopathological examination. CONCLUSION: PDT with
      Verteporfin can provide efficacious treatment of corneal neovascularization.

PMID- 25606322
TI  - Micromorphological evaluation of dentin treated with different desensitizing
      agents.
AB  - INTRODUCTION: The purpose of a desensitizing agent is a permanent coating or
      filling of dentin surface. Morphological analysis in vitro of this treated
      surface is essential to understand the interaction between desensitizing agent
      and hypersensitive dentin. The aim was to evaluate the morphology of four dentin
      surface treated with desensitizing agents. METHODS: This was an in vitro
      laboratory study, where fifteen specimens from extracted human premolars were
      obtained. The enamel was removed to expose the dentin surface, polished with
      silicon carbide abrasive papers and etched with 6% citric acid for 2 min.The
      specimens were randomly divided into 5 groups: G1 - without treatment (control)
      (C), G2 - fluoride varnish (FV), G3 - potassium oxalate (PO), G4 - 2-step self
      etching adhesive system (AS), G5 - diode laser (DL). The specimens were cleaved
      in the lingual buccaldirection, prepared for analysis by Scanning Electron
      Microscope and the surface and interior of the dentinal tubules were observed at
      1500* magnification. RESULTS: In the control group, the dentin etching promoted
      smear layer removal and exposure of dentinal tubules. In the group of fluoride
      varnish, a film was observed on the surface, with plugs of varnish into tubules.
      In the group of oxalate, partial obliteration of the tubular entrances was
      observed. In the group of the adhesive system, the tubules were obstructed
      through the formation of hybrid layer and a physical barrier on the surface. In
      the group of the diode laser, dentin melting and solidification with partial
      occlusion of dentinal tubules were observed. CONCLUSIONS: All desensitizing
      agents evaluated demonstrated ability to modify the surface of dentin, with
      partial or total occlusion of dentinal tubules. Thus, it is suggested to do more
      clinical studies to verify the effectiveness of the findings.

PMID- 25606323
TI  - Defocused irradiation mode of diode laser for conservative treatment of oral
      hemangioma.
AB  - Vascular lesions rise from abnormalities in blood vessels or endothelial
      proliferation. Capillary hemangiomas are formed by small capillaries surrounded
      by a layer of endothelial cells in a connective tissue stroma. Various treatments
      are used for these conditions like excisional surgery, sclerotherapy, and
      recently laser irradiation. In this case study, we report successful treatment of
      intraoral capillary hemangioma by gallium/aluminum/arsenide (GaAlAs) laser. A 29
      year old woman with a red lesion on the upper side of the right maxillary
      premolar was referred to private dental office. The Diode laser with wavelength
      of 810 nm was selected for treatment of the lesion in defocused mode by output
      power of 4 W in continuous mode. No bleeding was observed during surgery which
      provided better vision for surgeon and resulted in a minimally invasive
      procedure. According to results, Diode laser can be considered as a conservative
      modality in treatment of oral capillary hemangioma, especially in the esthetic
      zone. 

PMID- 25606324
TI  - Laser applications in orthodontics.
AB  - A laser is a collimated single wavelength of light which delivers a concentrated
      source of energy. Soon after different types of lasers were invented,
      investigators began to examine the effects of different wavelengths of laser
      energy on oral tissues, routine dental procedures and experimental applications.
      Orthodontists, along with other specialist in different fields of dentistry, can
      now benefit from several different advantages that lasers provide during the
      treatment process, from the beginning of the treatment, when separators are
      placed, to the time of resin residues removal from the tooth surface at the end
      of orthodontic treatment. This article outlines some of the most common usages of
      laser beam in orthodontics and also provides a comparison between laser and other
      conventional method that were the standard of care prior to the advent of laser
      in this field. 

PMID- 25606325
TI  - Evaluation of Accuracy of DIAGNOdent in Diagnosis of Primary and Secondary Caries
      in Comparison to Conventional Methods.
AB  - INTRODUCTION: Today the prevalence of teeth decays has considerably decreased.
      Related organizations and institutions mention several reasons for it such as
      improvement of decay diagnostic equipment and tools which are even capable of
      detecting caries in their initial stages. This resulted in reduction of costs for
      patients and remarkable increase in teeth life span. There are many methods for
      decay diagnostic, like: visual and radiographic methods, devices with
      fluorescence such as Quantitative light-induced fluorescence (QLF), Vista proof,
      Laser fluorescence (LF or DIAGNOdent), Fluorescence Camera (FC) and Digital
      radiography. Although DIAGNOdent is considered a valuable device for decay
      diagnostic ,there are concerns regarding its efficacy and accuracy. Considering
      the sensitivity of decaydiagnosis and the exorbitant annual expenses supported by
      government and people for caries treatment, finding the best method for early
      caries detection is of the most importance. Numerous studies were performed to
      compare different diagnostic methods with conflicting results. The objective of
      this study is a comparative review of the efficiency of DIAGNOdent in comparison
      to visual methods and radiographic methods in the diagnostic of teeth occlusal
      surfaces. METHODS: Search of PubMed, Google Scholar electronic resources was
      performed in order to find clinical trials in English in the period between 1998
      and 2013. Full texts of only 35 articles were available. CONCLUSION: Considering
      the sensitivity and specificity reported in the different studies, it seems that
      DIAGNOdent is an appropriate modality for caries detection as a complementary
      method beside other methods and its use alone to obtain treatment plan is not
      enough.

PMID- 25606326
TI  - In vitro evaluation of the effect of different laser irradiations on the enamel
      surfaces of teeth treated with home bleach procedure.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of dental surface
      treatment with Erbium-Doped Yttrium Aluminum Garnet(Er: YAG), Neodymium-Doped
      Yttrium Aluminium Garnet(Nd: YAG) and Carbon Dioxide Laser (CO2) lasers and
      sodium ascorbate to recently home bleached enamel by scanning electron microscope
      (SEM). METHODS: Thirty extracted human third molars were selected for this in
      vitro study. The teeth were randomly divided in two groups including home
      bleached group and control group (non-bleached). In group 1, the samples were
      bleached by home bleach technique. No bleaching procedure was done in second the
      group which served as control group.Then , the samples of two groups were divided
      to five subgroups as follow: Subgroup 1: treated using Nd:YAG laser with output
      power of 1 W, Subgroup 2: treated using Er:YAG laser with output power of 0.5 W,
      Subgroup 3: treated using CO2 laser with output power of 0.5 W, Subgroup 4:
      sodium ascorbate 10%, Subgroup 5: no treatment. After treatments, the surfaces
      were evaluated using Scanning Electron Microscope (SEM) analysis. RESULTS: The
      surfaces treated by Nd:YAG laser showed some melting and recrystallized areas and
      in some area droplet pattern was observed. But the surface treated by Er:YAG
      laser showed irregular and micro porous surface with flake pattern. CO2 laser
      treatment of home-bleached surfaces resulted in melting area and cracks. Sodium
      ascorbate did not change the home-bleached surface. CONCLUSION: Among different
      surface treatments used in this study, it seems that Er:YAG laser can best
      interact with home-bleached teeth.

PMID- 25606327
TI  - Temperature distribution simulation of the human eye exposed to laser radiation.
AB  - INTRODUCTION: Human eye is a sensitive part of human body with no direct
      protection and due to its lack of protection against the external heat waves,
      studying the temperature distribution of heat waves on the human eye is of utmost
      importance. Various lasers are widely used in medical applications such as eye
      surgeries. The most significant issue in the eye surgeries with laser is
      estimation of temperature distribution and its increase in eye tissues due to the
      laser radiation intensity. Experimental and invasive methods to measure the eye
      temperature usually have high risks. METHODS: In this paper, human eye has been
      modeled through studying the temperature distribution of three different laser
      radiations, using the finite element method. We simulated human eye under 1064 nm
      Neodymium-Doped Yttrium Aluminium Garnet (Nd: YAG) laser, 193 nm argon fluoride
      (ArF) excimer laser, and 1340 nm Neodymium doped Yttrium Aluminum Perovskite (Nd:
      YAP) laser radiation. RESULTS: The results show that these radiations cause
      temperature rise in retina, lens and cornea region, which will in turn causes
      serious damages to the eye tissues. CONCLUSION: This simulation can be a useful
      tool to study and predict the temperature distribution in laser radiation on the
      human eye and evaluate the risk involved in using laser to perform surgery.

PMID- 25606328
TI  - The effects of low intensity laser on clinical and electrophysiological
      parameters of carpal tunnel syndrome.
AB  - INTRODUCTION: Carpal Tunnel Syndrome (CTS) is the most common type of entrapment
      neuropathy. Conservative therapy is usually considered as the first step in the
      management of CTS. Low Level Laser Therapy (LLLT) is among the new physical
      modalities, which has shown therapeutic effects in CTS. The aim of the present
      study was to compare the effects of applying LASER and splinting together with
      splinting alone in patients with CTS. METHODS: Fifty patients with mild and
      moderate CTS who met inclusion criteria were included in this study. The disease
      was confirmed by electrodiagnostic study (EDx) and clinical findings. Patients
      were randomly divided into 3 groups. Group A received LLLT and splinting. Group B
      received sham LLLT+ splinting and group C received only splints. Group A received
      LLLT (50 mw and 880nm with total dose of 6 joule/cm(2)). Clinical and EDx
      parameters were evaluated before and after treatment (3 weeks and 2 months
      later). RESULTS: Electrophysiologic parameters and clinical findings including
      CTS provocative tests, Symptoms severity score (SSS), Functional Severity Score
      (FSS) and Visual Analogue Score (VAS) were improved in all three groups at 3
      weeks and 2 months after treatment. No significant changes were noticed between
      the three groups regarding clinical and EDX parameters. CONCLUSION: We found no
      superiority in applying Low Intensity Laser accompanying splinting to traditional
      treatment which means splinting alone in patients with CTS. However, future
      studies investigating LLLT with parameters other than the one used in this study
      may reveal different results in favor of LLLT.

PMID- 25606329
TI  - Histological Evaluation of Retina after Photo Disruption for Vitreous Humor by Q
      Switched Neodymium-Doped Yttrium Aluminium Garnet (Nd:YAG) Laser.
AB  - INTRODUCTION: Rabbits' eyes were exposed to vitreous humor liquefaction with Q -
      switched (sometimes called " giant pulses") Neodymium-Doped Yttrium Aluminium
      Garnet (Nd:YAG) laser using two different energy protocols (5 mJ X 100 pulse and
      10 mJ X 50 pulse)with and without vitamin C administration. The histological
      changes in the retina were investigated to evaluate the protective role of
      vitamin C. METHODS: The rabbits were divided into four main groups (n= 12 each).
      The first group was divided into three subgroups (n=4) and then treated with 5 mJ
      X 100 pulse (X means times) delivered to the anterior, middle and posterior
      vitreous humor respectively. The second group received a daily dose of 25 mg/Kg
      vitamin C for two weeks then was divided into three subgroups and treated with
      laser in the same manner as the first group.The third group was divided into
      three subgroups (n=4) and then treated with 10 mJ X 50 pulse delivered to the
      anterior, middle and posterior vitreous respectively. The fourth group received a
      daily dose of 25 mg/Kg vitamin C for two weeks then was divided into three
      subgroups and treated with laser in the same manner as the third group. After two
      weeks, rabbits were decapitated and histological examination for the retina was
      performed. RESULTS: The results showed that, the anterior vitreous group exposed
      to 5mJX100 pulse and supplemented with vitamin C, showed no obvious change.
      Furthermore, all other treated groups showed alteration in retina's tissues
      histology after laser. CONCLUSION: Application of Q-switched Nd: YAG laser in
      vitreous humor liquefaction induces changes in retina's layers. Although there
      were some sorts of improvements in retinas supplemented with vitamin C, it cannot
      protect them against laser oxidative damage.

PMID- 25606330
TI  - Comparison of Manual Tools, Ultrasonic and Erbium-Doped Yttrium Aluminum Garnet
      (Er:YAG) Laser on the Debridement Effect of the Surface of the Root of Teeth
      Suffering from Periodontitis.
AB  - INTRODUCTION: Periodontal diseases are considered as some of the most common
      reasons of teeth loss, which occur due to the aggregation of microbial plaque and
      other precipitations on the dental surfaces. In this study, the scaling effect
      using manual tools, ultrasonic machine and Erbium-Doped Yttrium Aluminum Garnet
      (Er:YAG)laser on the connection of the human gums connective tissue cells on the
      root surface of the teeth suffering from severe periodontitis will be compared.
      METHODS: After removal of the big precipitations with manual tools, Er:YAG laser
      light emission of Photona machine is used with respect to the following
      characteristics: wavelength: 2940MUm, each pulse: 100mJ, frequency: 10 pulse/sec,
      optic fiber with cross section 0.5x1.65mm, fiber tip angle with root surface: 15
      20 degrees with non-contact mode, 1.5mm farther than the root surface and pulse
      duration 230 very short. The gingival fibroblast cellular was incubated as a
      sample of the human gums connective tissue cells under 37C. These cells were
      departed from the culture medium after the cellular reproduction in the third
      passage.On the 3rd day after incubation, the gingival fibroblast cells morphology
      was studied by Scanning Electron Microscopy (SEM). RESULTS: The results of SEM
      images in the present study indicated the spread fibroblast cells with philopodia
      were found in all of 5 groups; untreated healthy group (control), untreated group
      suffering from periodontitis, the scaling effect using manual tools (Scaled
      Gracey), ultrasonic machine and Er:YAG laser. There is a meaningful difference
      among the three treatment groups (P<0.001) in the numbers of the fibroblast
      cells, while all the four treated groups had a meaningful difference with the
      positive control group (P < 0.001). CONCLUSION: The present study indicated that
      although various dental surfaces cleaning methods may be different in other
      aspects, but are similar concerning the fibroblasts morphology. Also in addition
      to power, laser emission time may also be effective in the cells morphology
      results.

PMID- 25606331
TI  - Diode laser application in soft tissue oral surgery.
AB  - INTRODUCTION: Diode laser with wavelengths ranging from 810 to 980 nm in a
      continuous or pulsed mode was used as a possible instrument for soft tissue
      surgery in the oral cavity. DISCUSSION: Diode laser is one of laser systems in
      which photons are produced by electric current with wavelengths of 810, 940 and
      980nm. The application of diode laser in soft tissue oral surgery has been
      evaluated from a safety point of view, for facial pigmentation and vascular
      lesions and in oral surgery excision; for example frenectomy, epulis fissuratum
      and fibroma. The advantages of laser application are that it provides relatively
      bloodless surgical and post surgical courses with minimal swelling and scarring.
      We used diode laser for excisional biopsy of pyogenic granuloma and gingival
      pigmentation. CONCLUSION: The diode laser can be used as a modality for oral soft
      tissue surgery.

PMID- 25606332
TI  - Oral mucositis prevention and management by therapeutic laser in head and neck
      cancers.
AB  - INTRODUCTION: Oral mucositis is considered a severe complication in cancer
      patients receiving radiotherapy or chemotherapy for head and neck cancer. The aim
      of this review study was to assess the effect of low level laser therapy for
      prevention and management of oral mucositis in cancer patients. METHODS: The
      electronic databases searched included Pubmed, ISI Web of Knowledge and Google
      scholar with keywords as "oral mucositis", "low level laser therapy" from 2000 to
      2013. RESULTS: The results of most studies showed that photobiomodulation (PBM)
      reduced the severity of mucositis. Also, it can delay the appearance of severe
      mucositis. CONCLUSION: Low level laser therapy is a safe approach for management
      and prevention of oral mucositis.

PMID- 25606333
TI  - 308nm excimer laser in dermatology.
AB  - 308nm xenon-chloride excimer laser, a novel mode of phototherapy, is an
      ultraviolet B radiation system consisting of a noble gas and halide. The aim of
      this systematic review was to investigate the literature and summarize all the
      experiments, clinical trials and case reports on 308-nm excimer laser in
      dermatological disorders. 308-nm excimer laser has currently a verified efficacy
      in treating skin conditions such as vitiligo, psoriasis, atopic dermatitis,
      alopecia areata, allergic rhinitis, folliculitis, granuloma annulare, lichen
      planus, mycosis fungoides, palmoplantar pustulosis, pityriasis alba, CD30+ lympho
      proliferative disorder, leukoderma, prurigo nodularis, localized scleroderma and
      genital lichen sclerosus. Although the 308-nm excimer laser appears to act as a
      promising treatment modality in dermatology, further large-scale studies should
      be undertaken in order to fully affirm its safety profile considering the
      potential risk, however minimal, of malignancy, it may impose. 

PMID- 25606334
TI  - Diffuse optical tomography: image reconstruction and verification.
AB  - INTRODUCTION: In this study, we intend to use diffuse optical Tomography (DOT) as
      a noninvasive, safe and low cost technique that can be considered as a functional
      imaging method and mention the importance of image reconstruction in accuracy and
      procession of image. One of the most important and fastest methods in image
      reconstruction is the boundary element method (BEM). This method is introduced
      and employed in our works. METHOD: Generally, to image a biological tissue we
      must obtain its optical properties. In order to reach this goal we benefit from
      diffusion equation because tissue is highly scattering medium. Diffusion equation
      is solved by boundary element equation (BEM) in our research. First, we assume a
      double layer phantom with different scattering and absorption coefficients to
      simulate and verify precession and accuracy of image reconstruction by BEM. Light
      absorption can be affected by volume fraction of blood in skin. For a specific
      skin species the volume fraction is calculated and then the results are compared
      with the reconstructed values obtained by BEM. Since the depth of tissue is
      important in light absorption a two layer phantom with known values is made and
      the depths of layers are reconstructed by BEM then they are compared with the
      expected values. A homogenous phantom with known scattering and absorption
      coefficients was made and then these coefficients were reconstructed by BEM.
      Finally, an inhomogeneous phantom (phantom with defect) whose defect was in a
      known position was made and the absorption and scattering coefficients were
      reconstructed and compared with real values. RESULTS: Comparison between real or
      simulated values and reconstructed values of scattering and absorption
      coefficients, volume fraction of blood and thickness of phantom layers by BEM
      shows maximum errors of 24%, 7% and 35%, respectively. CONCLUSION: Comparison
      between BEM data and real or simulated values shows an acceptabl eagreement.
      Consequently, we can rely on BEM as a beneficial method in diffuse optical
      tomography image reconstruction.

PMID- 25606335
TI  - The disinfecting efficacy of root canals with laser photodynamic therapy.
AB  - INTRODUCTION: Infecting microorganisms of the root canals are difficult to
      eliminate during endodontic treatment. In this study the effect of root canal
      disinfection with photodynamic therapy (PDT) at different time intervals in
      comparison to 2.5% sodium hypochlorite (NaOCl) irrigation and passive ultrasonic
      irrigation (PUI) in extracted teeth colonized with Enterococcus faecalis and
      Candida albicans was tested to assess which treatment reaches the best
      disinfection rate. METHODS: One hundred and fifty-six extracted single-rooted
      teeth were collected, sterilized, and incubated with Enterococcus faecalis (ATCC
      29212) and Candida albicans (ATCC 60193). The two groups were further divided
      into 6 groups depending on the treatment mode; HELBO((r))Endo Blue
      photosensitizer dye application followed by HELBO laser irradiation, with the
      output power 100 mW and emission of 660 nm, for a 1, 3 and 5 minutes, irrigation
      with 2.5% NaOCl, 10 second PUI with 2.5% NaOCl and control group. Flow cytometry
      and scanning electron microscopic (SEM) analysis were used to determine the
      effectiveness of the different disinfecting methods. RESULTS: The different
      disinfecting methods had a significantly different effect on the percent of dead
      cells (p<0.001). A statistical significance of dead cells between organisms
      (p<0.001) was observed. Interaction between the disinfecting method and both of
      organisms had shown the statistical significance (p=0.045). Percent of dead cells
      in treatment groups were significantly higher compared to control group for both
      organisms (p<0.001). CONCLUSIONS: PUI still remains the most effective method for
      disinfection of infected root canals in endodontics compared to hand
      instrumentation for both microorganisms. SEM analysis only confirmed the results.
      Other results ex vivo suggested that prolonging the time from 1 to 5 minutes of
      PDT increased the number of killed microorganisms significantly, therefore longer
      times of photodynamic therapy were recommended. Irrigation with 2.5% NaOCl showed
      similar results to 5 min irradiation.

PMID- 25606336
TI  - Evaluation of the effects of diode (980 nm) laser on gingival inflammation after
      nonsurgical periodontal therapy.
AB  - INTRODUCTION: Periodontitis is an inflammatory disease, for which, scaling and
      root planning(SRP) is the common approach for non-surgical control of
      inflammation. Using lasers is anotherapproach in the first phase of periodontal
      treatment for control of inflammation. Diode laserhas some beneficial effects
      such as acceleration of wound healing, promotion of angiogenesisand augmentation
      of growth factor release. Thus the aim of this study is the evaluation of
      diodelaser (980 nm) effect on gingival inflammation when it is used between the
      first and secondphase of periodontal treatment, in comparison with common
      treatment (SRP) modality alone. METHODS: In this study, 21 patients with moderate
      to severe chronic periodontitis were selectedand divided in to control group
      (SRP) and test group (SRP + laser). Two months after the lastscaling and laser
      radiation, indexes including gingival level (GL), bleeding on probing (BOP)and
      modified gingival index (MGI) were recorded and compared with baseline. RESULTS:
      Two months after the beginning of the study, all indices improved in both groups.
      Theindices were not different between two groups except for BOP which was lower
      in laser group. CONCLUSION: Based on overall improvement in parameters such as
      superiority of laser applicationin some indices, lack of thermal damage and
      gingival recession with the specific settings usedin this study, the application
      of laser as an adjunctive treatment together with common methodsis preferable.

PMID- 25606337
TI  - A Roughness Study of Ytterbium-Doped Potassium Yttrium Tungstate (YB: KYW) Thin
      Disk Femtosecond Ablated Dentin.
AB  - INTRODUCTION: The aim of this study was to evaluate the morphological changes and
      quantitatively assess the roughness of dentin after the ablation with a Ytterbium
      Doped Potassium Yttrium Tungstate (YB: KYW) thin-disk femtosecond pulsed laser of
      different fluences, scanning speeds and scanning distances. METHOD: Twelve
      extracted human premolars were sectioned into crowns and roots along the cementum
      enamel junction, and then the crowns were cut longitudinally into sheets about
      1.5 mm thick with a cutting machine. The dentin samples were fixed on a stage at
      focus plane. The laser beam was irradiated onto the samples through a
      galvanometric scanning system, so rectangular movement could be achieved. After
      ablation, the samples were examined with a scanning electron microscope and laser
      three-dimensional profile measurement microscope for morphology and roughness
      study.With increasing laser fluence, dentin samples exhibited more melting and
      resolidification of dentin as well as debris-like structure and occluded parts of
      dentinal tubules. RESULTS: When at the scanning speed of 2400mm/s and scanning
      distance of 24MUm, the surface roughness of dentin ablated with femtosecond
      pulsed laser decreased significantly and varied between values of dentin surface
      roughness grinded with two kinds of diamond burs with different grits. When at
      the scanning speed of 1200mm/s and scanning distance of 12MUm, the surface
      roughness decreased slightly, and the surface roughness of dentin ablated with
      femtosecond pulsed laser was almost equal to that grinded with a low grit diamond
      bur. CONCLUSION: This study showed that increased laser influence may lead to
      more collateral damage and lower dentin surface roughness, while scanning speed
      and scanning distance were also negatively correlated with surface roughness.
      Adequate parameters should be chosen to achieve therapeutic benefits, and
      different parameters can result in diverse ablation results.

PMID- 25606338
TI  - The effect of polarized polychromatic noncoherent light (bioptron) therapy on
      patients with carpal tunnel syndrome.
AB  - INTRODUCTION: To study the effects of Polarized Polychromatic Noncoherent Light
      (Bioptron) therapy on patients with carpal tunnel syndrome (CTS). METHODS: This
      study was designed as a randomized clinical trial. Forty four patients with mild
      or moderate CTS (confirmed by clinical and electrodiagnostic studies) were
      assigned randomly into two groups (intervention and control goups). At the
      beginning of the study, both groups received wrist splinting for 8 weeks.
      Bioptron light was applied for the intervention group (eight sessions, for
      3/weeks). Bioptron was applied perpendicularly to the wrist from a 10 centimeter
      sdistance. Pain severity and electrodiagnostic measurements were compared from
      before to 8 weeks after initiating each treatment. RESULTS: Eight weeks after
      starting the treatments, the mean of pain severity based on Visual Analogue Scale
      (VAS) scores decreased significantly in both groups. Median Sensory Nerve Action
      Potential (SNAP) latency decreased significantly in both groups. However, other
      electrophysiological findings (median Compound Motor Action Potential (CMAP)
      latency and amplitude, also SNAP amplitude) did not change after the therapy in
      both groups. There was no meaningful difference between two groups regarding the
      changes in the pain severity. CONCLUSION: Bioptron with the above mentioned
      parameters led to therapeutic effects equal to splinting alone in patients with
      carpal tunnel syndrome. However, applying Bioptron with different therapeutic
      protocols and light parameters other than used in this study, perhaps longer
      duration of therapy and long term assessment may reveal different results
      favoring Bioptron therapy.

PMID- 25606339
TI  - One visit providing desirable smile by laser application.
AB  - INTRODUCTION: Providing desirable smile is one of the main concerns in cosmetic
      dentistry. Hyperpigmentation is one of the esthetic concerns especially in gummy
      smile patients. Lasers with different wavelength are used for oral surgery
      including Carbon Dioxide Laser (CO2), Neodymium-Doped Yttrium Aluminium Garnet
      (Nd:YAG), Erbium family and diode laser. In this case, all esthetic procedures
      including gingival depigmentation, caries detection and removal were done by
      laser technology in one session. CASE STUDY: A 40- year-old male with a chief
      complaint of black gingiva in upper jaw was referred. The right side of maxillary
      was anesthetized and depigmentation was done by Erbium, Chromium doped Yttrium
      Scandium Gallium Garnet (Er-Cr: YSGG) laser. Due to scores obtained from
      Diagnodent which indicated caries in dentin, the cavities were prepared by Er
      Cr:YSGG laser. The cavities were restored by composite resin. The patient was
      advised to keep oral hygiene instructions and use mouthwash. RESULTS: The patient
      reported no pain after surgery and did not use any systemic antibiotic. After 4
      weeks, complete healing was observed. CONCLUSION: Considering acceptable clinical
      outcome, Er-Cr: YSGG laser can be considered as an effective method for
      combination of soft and hard tissue treatment.

PMID- 25606340
TI  - Argon prevents the development of locomotor sensitization to amphetamine and
      amphetamine-induced changes in mu opioid receptor in the nucleus accumbens.
AB  - Systemic administration of gamma-amino-butyric acid type A (GABA-A) and
      benzodiazepine receptor agonists has been reported to block the development of
      locomotor sensitization to amphetamine. Here, we investigated whether the non
      anesthetic noble gas argon, shown to possess agonistic properties at these
      receptors, may block the acquisition of amphetamine-induced locomotor
      sensitization and mu opioid receptor activation in the nucleus accumbens. Rats
      were pretreated with saline solution or amphetamine (1 mg/kg) from day 1 to day 3
      and then exposed, immediately after injection of amphetamine, to medicinal air or
      argon at 75 vol% (with the remainder being oxygen). After a 3-day period of
      withdrawal, rats were challenged with amphetamine on day 7. Rats pretreated with
      amphetamine and argon had lower locomotor activity (U = 5, P < 0.005) and mu
      opioid receptor activity in the nucleus accumbens (U = 0, P < 0.001) than rats
      pretreated with amphetamine and air. In contrast, argon had effect on locomotor
      and mu receptor activity neither in rats pretreated with saline and challenged
      with amphetamine (acute amphetamine) nor in rats pretreated and challenged with
      saline solution (controls). These results indicate that argon inhibits the
      development of both locomotor sensitization and mu opioid receptor activation
      induced by repeated administration of amphetamine. 

PMID- 25606341
TI  - Exogenous hydrogen sulfide mitigates the fatty liver in obese mice through
      improving lipid metabolism and antioxidant potential.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver
      disease in the world. Hydrogen sulfide (H2S) plays an important role in
      physiology and pathophysiology of liver. However, whether exogenous H2S could
      mitigate the hepatic steatosis in mice remains unclear. The aim of this study is
      to evaluate the effects of H2S on fatty liver. METHODS: C57BL/6 mice were fed
      with either a high-fat diet (HFD) or a normal fat diet (NFD) for 16 weeks. After
      12 weeks of feeding, the HFD-fed mice were injected one time per day with NaHS or
      saline for the followed 4 weeks. RESULTS: Compared to NFD, HFD could induce an
      accumulation of lipids in liver and a damage of hepatic structure. Compared to
      saline treatment, in the liver of HFD fed mice H2S treatment could significantly
      (1) recover the structure; (2) decrease the accumulation of lipids including
      triglyceride (TG) and total cholesterol (TC); (3) decrease the expression of
      fatty acid synthase (FAS) and increase the expression of carnitine
      palmitoyltransferase-1 (CPT-1); (4) reduce malondialdehyde (MDA) levels; (5)
      increase the activities of superoxide dismutase (SOD) and glutathione peroxidase
      (GPx). CONCLUSION: H2S could mitigate the fatty liver by improving lipid
      metabolism and antioxidant potential in HFD-induced obese mice.

PMID- 25606342
TI  - Vitamin D and cinacalcet administration pre-transplantation predict
      hypercalcaemic hyperparathyroidism post-transplantation: a case-control study of
      355 deceased-donor renal transplant recipients over 3 years.
AB  - BACKGROUND: The effects of pre-transplantation medication for secondary
      hyperparathyroidism on post-transplantation parathyroid hormone (PTH) and calcium
      levels have not yet been conclusively determined. Therefore, this study sought to
      determine the level of off-label use of cinacalcet and to determine predictors of
      its administration during the long-term follow-up of a cohort of individuals who
      received deceased-donor renal transplants. Furthermore, safety considerations
      concerning the off-label use of cinacalcet are addressed. METHODS: This was a
      case-control study of 355 stable renal transplant recipients. The patient cohort
      was divided into two groups. Transplant group A comprised patients who did not
      receive cinacalcet treatment, and transplant group B comprised patients who
      received cinacalcet treatment during follow-up after renal transplantation. The
      characteristics of the patients were evaluated to determine predictors of
      cinacalcet use after successful renal transplantation. RESULTS: Compared with the
      control individuals (n = 300), the cinacalcet-treated individuals (n = 55) had
      significantly higher PTH levels at 4 weeks post-transplantation (20.3 +/- 1.6
      versus 40.7 +/- 4.0 pmol/L, p = 0.0000) when they were drug naive. At 3.2 years
      post-transplantation, cinacalcet-treated patients showed higher PTH (26.2 +/- 2.3
      versus 18.4 +/- 2.3 pmol/L, p = 0.0000), higher calcium (2.42 +/- 0.03 versus
      2.33 +/- 0.01 mmol/L, p = 0.0045) and lower phosphate (0.95 +/- 0.04 versus 1.06
      +/- 0.17 mmol/L, p = 0.0021) levels. Individuals in the verum group were more
      likely to receive cinacalcet therapy (45.5% versus 14.3%, p = 0.0000), and they
      had higher pill burdens for the treatment of hyperparathyroidism (1.40 +/- 0.08
      versus 0.72 +/- 0.03 pills per patient, p = 0.0000) whilst they were on the
      waiting list for transplantation. Regression analysis confirmed the associations
      between hypercalcaemic hyperparathyroidism and PTH levels at 4 weeks post
      transplantation (p = 0.0001), cinacalcet use (p = 0.0000) and the preoperative
      total pill burden (p = 0.0000). Renal function was the same in both groups.
      CONCLUSIONS: Parathyroid gland dysfunction pre-transplantation translates into
      clinically relevant hyperparathyroidism post-transplantation, despite patients
      being administered more intensive treatment whilst on dialysis. PTH levels at 4
      weeks post-transplantation might serve as a marker for the occurrence of
      hypercalcaemic hyperparathyroidism during follow-up.

PMID- 25606343
TI  - Evaluation of chromosomal aberrations caused by air pollutants in some taxi
      drivers from two polluted districts of urban Tehran and its comparison with
      drivers from rural areas of Lahijan: a pilot study.
AB  - BACKGROUND: Chromosome instability is the most common form of genomic
      instability. Genomic instability can lead to tumorogenesis. High level of
      chromosomal aberrations in peripheral blood lymphocytes can be used as a
      biomarker for cancer. Air pollution is one of the most important factors that
      cause chromosomal instability (CIN). In this comparative study we used classic
      Cytogenetic technique to analyze the effects of air pollutants on chromosome
      stability. We collected peripheral blood from 30 taxi drivers of two polluted
      districts (districts 6 and 7) in Tehran and 30 taxi drivers from rural areas of
      Lahijan, north of Iran. RESULTS: Comparison of the level of chromosome breakage
      in the two groups showed an increased level of chromosome breakage in the drivers
      from polluted districts of Tehran, although not significant, using Fisher exact
      test (p-value = 0.300). However, the overall chromosome aberration rate
      (including both chromosome and chromatid gaps), the difference was significant
      using Chi-square test (p-value = 0.012). CONCLUSION: An increased level of
      chromosome aberration was present in the drivers from polluted districts of
      Tehran compared to drivers from non-polluted areas in Lahijan.

PMID- 25606344
TI  - Disinfection of raw wastewater and activated sludge effluent using Fenton like
      reagent.
AB  - BACKGROUND AND OBJECTIVES: Water shortage problems have led to find either new
      water resources or improve wastewater treatment technologies in order to reuse.
      Due to less performance of previous units in microbial removal, disinfection has
      become a necessary step in wastewater treatment plants. In the present study
      performance of hydrogen peroxide (HP) and modified Fenton's reagent (HP + Cu(++))
      was considered for the disinfection of raw wastewater (RW) and activated sludge
      effluent (ASE). MATERIALS AND METHODS: Plastic containers of 10-liter volume each
      were used for RW and ASE sampling. Microbiological analyses of the RW and ASE
      were performed in triplicate; before and after the disinfection process. Fecal
      coliforms were analyzed by the direct (without enrichment) multiple fermentation
      tube procedure. RESULTS: The results showed that using HP alone did not have any
      significant disinfection capability. In RW and ASE, the highest dose used in this
      study could reduce fecal coliforms (FC)s by only 1.54 and 1.16 log-inactivation,
      respectively. However, Maximum removal efficiency of modified Fenton in RW and
      ASE was 4.63 and 3.41 log-inactivation, respectively. The results suggested that
      Cu(++) ions used in combination with H2O2 produced very rigorous synergistic
      effect, and HP disinfection capacity increased significantly. CONCLUSION:
      Hydrogen peroxide, when applied alone, was not successful in disinfecting of
      either RW or ASE, and neither the WHO guideline nor the Iranian standard could be
      met. However, modified Fenton showed very significant disinfection potential and
      could reduce FCs under World Health Organization (WHO) guideline and Iranian
      national standard for agricultural irrigation.

PMID- 25606345
TI  - Influence of bioaugmentation on biodegradation of phenanthrene-contaminated soil
      by earthworm in lab scale.
AB  - BACKGROUND: Use of earthworm to eliminate the phenanthrene from the soil
      (bioaccumulation) is developed as an economical method. Bioaugmentation of
      microorganism was used for promotion of bioaccumulation by earthworm. The aim of
      this study was to determine the bioaccumulation or biodegradation of phenanthrene
      by Eisenia fetida and bacterial consortium in polluted soil. METHODS: The amount
      of 0.4 kg of the polluted soil in the ratio of 10 and 30 mg phenanthrene per kg
      of dry soil was transferred into each pot. Afterwards, bacteria and earthworms
      were added to each pot in separate and combination. The samples were kept under
      field conditions, and the retention concentrations of phenanthrene were analyzed
      after 8 weeks. RESULTS: Results showed that the Eisenia fetida was able to
      significantly remove phenanthrene from the polluted soil samples. Bioaccumulation
      and bioaugmentation alone have the removal efficiency of 60.24% and 50.3%,
      respectively. In the combined mode, phenanthrene removal efficiency was 63.81%.
      CONCLUSIONS: The current study indicated that the use of earthworms, could
      improve both phenanthrene bioavailability and microbial activity, which led to
      enhancing removal of carbon-based pollutants.

PMID- 25606346
TI  - Approximation Bayesian Computation.
AB  - Approximation Bayesian computation [ABC] is an analysis approach that has arisen
      in response to the recent trend to collect data that is of a magnitude far higher
      than has been historically the case. This has led to many existing methods become
      intractable because of difficulties in calculating the likelihood function. ABC
      circumvents this issue by replacing calculation of the likelihood with a
      simulation step in which it is estimated in one way or another. In this review we
      give an overview of the ABC approach, giving examples of some of the more popular
      specific forms of ABC. We then discuss some of the areas of most active research
      and application in the field, specifically, choice of low-dimensional summaries
      of complex datasets and metrics for measuring similarity between observed and
      simulated data. Next, we consider the question of how to do model selection in an
      ABC context. Finally, we discuss an area of growing prominence in the ABC world,
      use of ABC methods in genetic pathway inference.

PMID- 25606347
TI  - Technology-Based Innovations in Child Maltreatment Prevention Programs: Examples
      from SafeCare(r)
AB  - Each year, hundreds of thousands of children in the U.S. are victims of child
      maltreatment. Experts recommend behavioral, skill-based parent training programs
      as a strategy for the prevention of child abuse and neglect. These programs can
      be enhanced using innovative technology strategies. This paper presents a brief
      history of the use of technology in SafeCare(r), a home visiting program shown to
      prevent child neglect and physical abuse, and highlights current work that takes
      a technology-based hybrid approach to SafeCare delivery. With this unique
      approach, the provider brings a tablet computer to each session, and the parent
      interacts with the software to receive psychoeducation and modeling of target
      skills. The provider and parent then work together to practice the targeted
      skills until mastery is achieved. Initial findings from ongoing research of both
      of these strategies indicate that they show potential for improving engagement
      and use of positive parenting skills for parents and ease of implementation for
      providers. Future directions for technology enhancements in SafeCare are also
      presented.

PMID- 25606348
TI  - Receptivity and Preferences in Cancer Risk Reduction Lifestyle Programs: A Survey
      of Colorectal Cancer Family Members.
AB  - BACKGROUND: Cancer is a shared family experience, and thus the purpose of this
      study was to assess receptivity and preferences for cancer risk reduction
      programs among at-risk family members with two or more relatives affected with
      colorectal cancer (CRC). METHODS: The sample comprised 401 at-risk family members
      with two or more relatives affected with CRC from the Colon Cancer Family
      Registry. In March 2009, respondents completed a mailed survey assessing
      receptivity and preferences for participating in cancer risk reduction programs
      and evaluated their relationship to demographic, medical, and psychosocial
      variables. Multivariable generalized estimating equation approaches were used to
      model preferences. RESULTS: Overall, 81% of respondents were receptive to a
      lifestyle cancer risk reduction program; of these, about half (54%) preferred to
      participate with their family. Program preferences included: weight management
      (36%) and nutrition (31%); delivered through the internet (41%) or mail (39%). In
      a multivariate model, a greater level of concern about cancer (p<0.001), female
      gender (p=0.002), and higher education (p=0.016) were significantly correlated
      with willingness to participate in lifestyle programs. CONCLUSIONS: Family
      members of those with CRC are receptive to cancer risk reduction programs that
      focus on weight management and nutrition delivered via the internet or mail.
      Future research is needed to determine how best to incorporate a family-based
      approach that addresses the cancer experience when designing lifestyle
      intervention programs.

PMID- 25606349
TI  - Household Air Pollution (HAP) and Cancer: What (HAP)pens Next?

PMID- 25606351
TI  - Expressive Writing Can Impede Emotional Recovery Following Marital Separation.
AB  - Marital separation and divorce are common life events that increases risk for
      poor health outcomes, yet few intervention studies explore how to mitigate this
      increased risk. This study implemented an expressive writing (EW; see Pennebaker,
      1997) intervention for adults who experienced a recent marital separation. Ninety
      participants (32 men) were randomly assigned to and completed one of three
      experimental writing tasks: traditional EW, a novel (narrative-based) type of EW
      or control writing. Up to nine months after this writing, participants judged to
      be actively engaged in a search for meaning concerning their separation reported
      significantly worse emotional outcomes when assigned to either EW condition
      relative to control writing. Within the control condition, those participants
      actively engaged in a search for meaning reported the lowest levels of separation
      related disturbance. We discuss these results in terms of the factors that may
      limit and promote psychological recovery following marital separation.

PMID- 25606352
TI  - Application of ITS2 metabarcoding to determine the provenance of pollen collected
      by honey bees in an agroecosystem.
AB  - PREMISE OF THE STUDY: Melissopalynology, the identification of bee-collected
      pollen, provides insight into the flowers exploited by foraging bees. Information
      provided by melissopalynology could guide floral enrichment efforts aimed at
      supporting pollinators, but it has rarely been used because traditional methods
      of pollen identification are laborious and require expert knowledge. We approach
      melissopalynology in a novel way, employing a molecular method to study the
      pollen foraging of honey bees (Apis mellifera) in a landscape dominated by field
      crops, and compare these results to those obtained by microscopic
      melissopalynology. * METHODS: Pollen was collected from honey bee colonies in
      Madison County, Ohio, USA, during a two-week period in midspring and identified
      using microscopic methods and ITS2 metabarcoding. * RESULTS: Metabarcoding
      identified 19 plant families and exhibited sensitivity for identifying the taxa
      present in large and diverse pollen samples relative to microscopy, which
      identified eight families. The bulk of pollen collected by honey bees was from
      trees (Sapindaceae, Oleaceae, and Rosaceae), although dandelion (Taraxacum
      officinale) and mustard (Brassicaceae) pollen were also abundant. * DISCUSSION:
      For quantitative analysis of pollen, using both metabarcoding and microscopic
      identification is superior to either individual method. For qualitative analysis,
      ITS2 metabarcoding is superior, providing heightened sensitivity and genus-level
      resolution.

PMID- 25606350
TI  - Mobilizable Rolling-Circle Replicating Plasmids from Gram-Positive Bacteria: A
      Low-Cost Conjugative Transfer.
AB  - Conjugation is a key mechanism for horizontal gene transfer in bacteria. Some
      plasmids are not self-transmissible but can be mobilized by functions encoded in
      trans provided by other auxiliary conjugative elements. Although the transfer
      efficiency of mobilizable plasmids is usually lower than that of conjugative
      elements, mobilizable plasmidsare more frequently found in nature. In this sense,
      replication and mobilization can be considered as important mechanisms
      influencing plasmid promiscuity. Here we review the present available information
      on two families of small mobilizable plasmids from Gram-positive bacteria that
      replicate via the rolling-circle mechanism. One of these families, represented by
      the streptococcal plasmid pMV158, is an interesting model since it contains a
      specific mobilization module (MOBV) that is widely distributed among mobilizable
      plasmids. We discuss a mechanism in which the promiscuity of the pMV158 replicon
      is based on the presence of two origins of lagging strand synthesis. The current
      strategies to assess plasmid transfer efficiency as well as to inhibit
      conjugative plasmid transfer are presented. Some applications of these plasmids
      as biotechnological tools are also reviewed.

PMID- 25606353
TI  - A method for eliminating bacterial contamination from in vitro moss cultures.
AB  - PREMISE OF THE STUDY: Bacterial contamination is a major problem in plant tissue
      culture, resulting in loss of experimental strains or preventing use of field
      collected isolates. Here we evaluated an agar embedding method for eliminating
      bacteria from experimental cultures of the mosses Ceratodon purpureus and
      Physcomitrella patens. * METHODS AND RESULTS: We blended moss protonema that had
      been inoculated with bacteria and embedded the cell fragments in antibiotic
      containing, low-concentration agar. The plants were placed in a growth chamber
      and allowed to grow until the moss grew out of the media. The plants were then
      transferred to new plates and observed for contamination. The embedding method
      consistently outperformed standard procedures. * CONCLUSIONS: The embedding
      method places moss in direct contact with antibiotics, arresting bacterial
      replication and allowing moss to outgrow contamination. We anticipate this method
      will prove valuable for other plants capable of clonal propagation by blending.

PMID- 25606354
TI  - Fourteen polymorphic microsatellite markers for the threatened Arnica montana
      (Asteraceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed to investigate
      population genetic structure in the threatened species Arnica montana. * METHODS
      AND RESULTS: Fourteen microsatellite markers with di-, tetra-, and hexanucleotide
      repeat motifs were developed for A. montana using 454 pyrosequencing without and
      with library-enrichment methods, resulting in 56,545 sequence reads and 14,467
      sequence reads, respectively. All loci showed a high level of polymorphism, with
      allele numbers ranging from four to 11 in five individuals from five populations
      (25 samples) and an expected heterozygosity ranging from 0.192 to 0.648 across
      the loci. * CONCLUSIONS: This set of microsatellite markers is the first one
      described for A. montana and will facilitate conservation genetic applications as
      well as the understanding of phylogeographic patterns in this species.

PMID- 25606355
TI  - Positional cloning in maize (Zea mays subsp. mays, Poaceae).
AB  - PREMISE OF THE STUDY: Positional (or map-based) cloning is a common approach to
      identify the molecular lesions causing mutant phenotypes. Despite its large and
      complex genome, positional cloning has been recently shown to be feasible in
      maize, opening up a diverse collection of mutants to molecular characterization.
      * METHODS AND RESULTS: Here we outline a general protocol for positional cloning
      in maize. While the general strategy is similar to that used in other plant
      species, we focus on the unique resources and approaches that should be
      considered when applied to maize mutants. * CONCLUSIONS: Positional cloning
      approaches are appropriate for maize mutants and quantitative traits, opening up
      to molecular characterization the large array of genetic diversity in this
      agronomically important species. The cloning approach described should be broadly
      applicable to other species as more plant genomes become available.

PMID- 25606356
TI  - Microsatellite development and flow cytometry in the African tree genus Afzelia
      (Fabaceae, Caesalpinioideae) reveal a polyploid complex.
AB  - PREMISE OF THE STUDY: Microsatellites were developed in the vulnerable African
      rainforest tree Afzelia bipindensis to investigate gene flow patterns. * METHODS
      AND RESULTS: Using 454 GS-FLX technique, 16 primer sets were identified and
      optimized, leading to 11 polymorphic and readable markers displaying each six to
      25 alleles in a population. Up to four alleles per individual were found in each
      of the loci, without evidence of fixed heterozygosity, suggesting an
      autotetraploid genome. Cross-amplification succeeded for all loci in the African
      rainforest species A. pachyloba and A. bella, which appeared tetraploid, and for
      most loci in the African woodland species A. africana and A. quanzensis, which
      appeared diploid, but failed in the Asian species A. xylocarpa. Flow cytometry
      confirmed the suspected differences in ploidy. * CONCLUSIONS: African Afzelia
      species are diploid or tetraploid, a situation rarely documented in tropical
      trees. These newly developed microsatellites will help in the study of their
      mating system and gene flow patterns.

PMID- 25606357
TI  - Development and characterization of microsatellite loci in the mistletoe
      Psittacanthus schiedeanus (Loranthaceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for the parasitic
      Psittacanthus schiedeanus, a common mistletoe species on cloud forest-adapted
      tree hosts in Mesoamerica, to investigate intraspecific genetic patterns of
      diversity and genetic structure. * METHODS AND RESULTS: Using an enriched
      library, 10 polymorphic microsatellite loci were developed in P. schiedeanus. All
      loci consisted of dinucleotide repeats. Average alleles per locus were 12 (4-17),
      and a total of 120 alleles were recorded across 39 individuals from four
      populations in Mexico. Primers were tested in 11 additional species, but only
      amplified successfully in P. calyculatus and P. angustifolius. * CONCLUSIONS: The
      polymorphic loci described will be useful in studies of genetic diversity and
      genetic population differentiation in natural populations of these parasitic
      plants, and will provide valuable information to understand the importance of
      host distribution.

PMID- 25606358
TI  - Simple sequence repeat markers for the endangered species Clianthus puniceus and
      C. maximus (Fabaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for Clianthus
      puniceus using a shotgun sequencing library and tested for cross amplification in
      the closely related C. maximus to inform population management of these two
      endangered species. * METHODS AND RESULTS: We constructed a shotgun sequencing
      library using a Roche 454 sequencer and searched the resulting data set for
      putative microsatellite regions. We optimized 12 of these regions to produce
      polymorphic markers for Clianthus. We tested these markers on four populations of
      C. maximus and on four C. puniceus individuals of known provenance. Alleles per
      locus ranged from two to nine, while observed and expected heterozygosities per
      locus ranged from 0.000 to 1.000 and 0.178 to 0.600, respectively. * CONCLUSIONS:
      These markers will be valuable for ongoing monitoring of the genetic variation in
      naturally occurring populations of Clianthus and for the selection of individuals
      for revegetation projects in the species' former range.

PMID- 25606359
TI  - Translational research guided by animal studies in Fragile X Disorders.

PMID- 25606360
TI  - Current research, diagnosis, and treatment of fragile X-associated tremor/ataxia
      syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by a premutation
      CGG-repeat expansion in the 5'UTR of the fragile X mental retardation 1 (FMR1)
      gene. The classical clinical manifestations include tremor, cerebellar ataxia,
      cognitive decline and psychiatric disorders. Other less frequent features are
      peripheral neuropathy and autonomic dysfunction. Cognitive decline, a form of
      frontal subcortical dementia, memory loss and executive function deficits are
      also characteristics of this disorder. In this review, we present an expansion of
      recommendations for genetic testing for adults with suspected premutation
      disorders and provide an update of the clinical, radiological and molecular
      research of FXTAS, as well as the current research in the treatment for this
      intractable complex neurodegenerative genetic disorder. 

PMID- 25606361
TI  - Serotonin dysregulation in Fragile X Syndrome: implications for treatment.
AB  - Fragile X Syndrome (FXS) is a trinucleotide repeat disorder that results in the
      silencing of the Fragile X Mental Retardation 1 gene (FMR1), leading to a lack of
      the FMR1 protein (FMRP). FMRP is an mRNA-binding protein that regulates the
      translation of hundreds of mRNAs important for synaptic plasticity. Several of
      these pathways have been identified and have guided the development of targeted
      treatments for FXS. Here we present evidence that serotonin is dysregulated in
      FXS and treatment with the selective serotonin reuptake inhibitor (SSRI)
      sertraline may be beneficial for individuals with FXS, particularly in early
      childhood. 

PMID- 25606364
TI  - Participation of underrepresented minority children in clinical trials for
      Fragile X syndrome and other neurodevelopmental disorders.
AB  - The purpose of this study was to identify demographic data, motivational factors
      and barriers for participation in clinical trials (CTs) at the University of
      California Davis, MIND Institute. We conducted a cross-sectional survey in 100
      participants (81 females and 19 males). The participants had high education
      levels (only 2% had not completed high school), a mean age of 44 years (SD +/-
      9.899) and had at least one child with a neurodevelopmental disorder. The
      diagnosis of Fragile X syndrome (FXS) had a significant association with past
      participation in CTs (p < 0.001). A statistical significance for age of diagnosis
      and participation in CTs was also found (z = -2.01, p = 0.045). The motivating
      factors were to help find cures/treatments for neurodevelopmental disorders and
      to relieve symptoms related to child's diagnosis. Factors explaining lack of
      participation, unwillingness to participate or unsure of participation were: lack
      of information/knowledge about the trials, time commitment to participation
      (screening, appointments, assessments, laboratory tests, etc.) and low annual
      household income. These results show that a portion of underrepresented
      minorities (URM) not participating in CTs are willing to participate and suggests
      that reducing barriers, particularly lack of knowledge/information and time
      commitment to trials are needed to improve recruitment. 

PMID- 25606363
TI  - Fragile X spectrum disorders.
AB  - The fragile X mental retardation 1 gene (FMR1), which codes for the fragile X
      mental retardation 1 protein (FMRP), is located at Xp27.3. The normal allele of
      the FMR1 gene typically has 5 to 40 CGG repeats in the 5' untranslated region;
      abnormal alleles of dynamic mutations include the full mutation (> 200 CGG
      repeats), premutation (55-200 CGG repeats) and the gray zone mutation (45-54 CGG
      repeats). Premutation carriers are common in the general population with
      approximately 1 in 130-250 females and 1 in 250-810 males, whereas the full
      mutation and Fragile X syndrome (FXS) occur in approximately 1 in 4000 to 1 in
      7000. FMR1 mutations account for a variety of phenotypes including the most
      common monogenetic cause of inherited intellectual disability (ID) and autism
      (FXS), the most common genetic form of ovarian failure, the fragile X-associated
      primary ovarian insufficiency (FXPOI, premutation); and fragile X-associated
      tremor/ataxia syndrome (FXTAS, premutation). The premutation can also cause
      developmental problems including ASD and ADHD especially in boys and
      psychopathology including anxiety and depression in children and adults. Some
      premutation carriers can have a deficit of FMRP and some unmethylated full
      mutation individuals can have elevated FMR1 mRNA that is considered a premutation
      problem. Therefore the term "Fragile X Spectrum Disorder" (FXSD) should be used
      to include the wide range of overlapping phenotypes observed in affected
      individuals with FMR1 mutations. In this review we focus on the phenotypes and
      genotypes of children with FXSD. 

PMID- 25606362
TI  - Modeling fragile X syndrome in the Fmr1 knockout mouse.
AB  - Fragile X Syndrome (FXS) is a commonly inherited form of intellectual disability
      and one of the leading genetic causes for autism spectrum disorder. Clinical
      symptoms of FXS can include impaired cognition, anxiety, hyperactivity, social
      phobia, and repetitive behaviors. FXS is caused by a CGG repeat mutation which
      expands a region on the X chromosome containing the FMR1 gene. In FXS, a full
      mutation (> 200 repeats) leads to hypermethylation of FMR1, an epigenetic
      mechanism that effectively silences FMR1 gene expression and reduces levels of
      the FMR1 gene product, fragile X mental retardation protein (FMRP). FMRP is an
      RNA-binding protein that is important for the regulation of protein expression.
      In an effort to further understand how loss of FMR1 and FMRP contribute to FXS
      symptomology, several FXS animal models have been created. The most well
      characterized rodent model is the Fmr1 knockout (KO) mouse, which lacks FMRP
      protein due to a disruption in its Fmr1 gene. Here, we review the behavioral
      phenotyping of the Fmr1 KO mouse to date, and discuss the clinical relevance of
      this mouse model to the human FXS condition. While much remains to be learned
      about FXS, the Fmr1 KO mouse is a valuable tool for understanding the
      repercussions of functional loss of FMRP and assessing the efficacy of
      pharmacological compounds in ameliorating the molecular and behavioral phenotypes
      relevant to FXS. 

PMID- 25606365
TI  - Distribution of AGG interruption patterns within nine world populations.
AB  - The CGG trinucleotide repeat within the FMR1 gene is associated with multiple
      clinical disorders, including fragile X-associated tremor/ataxia syndrome,
      fragile X-associated primary ovarian insufficiency, and fragile X syndrome.
      Differences in the distribution and prevalence of CGG repeat length and of AGG
      interruption patterns have been reported among different populations and
      ethnicities. In this study we characterized the AGG interruption patterns within
      3,065 normal CGG repeat alleles from nine world populations including Australia,
      Chile, United Arab Emirates, Guatemala, Indonesia, Italy, Mexico, Spain, and
      United States. Additionally, we compared these populations with those previously
      reported, and summarized the similarities and differences. We observed
      significant differences in AGG interruption patterns. Frequencies of longer
      alleles, longer uninterrupted CGG repeat segments and alleles with greater than 2
      AGG interruptions varied between cohorts. The prevalence of fragile X syndrome
      and FMR1 associated disorders in various populations is thought to be affected by
      the total length of the CGG repeat and may also be influenced by the AGG
      distribution pattern. Thus, the results of this study may be important in
      considering the risk of fragile X-related conditions in various populations. 

PMID- 25606366
TI  - Addictive substances may induce a rapid neurological deterioration in fragile X
      associated tremor ataxia syndrome: A report of two cases.
AB  - A debilitating late-onset disorder of the premutation in the FMR1 gene is the
      neurodegenerative disorder fragile X-associated tremor ataxia syndrome (FXTAS).
      We report two patients with FXTAS who have a history of substance abuse (opiates,
      alcohol, and cocaine) which may have exacerbated their rapid neurological
      deterioration with FXTAS. There has been no case report regarding the role of
      substance abuse in onset, progression, and severity of FXTAS symptoms. However,
      research has shown that substance abuse can have a negative impact on several
      neurodegenerative diseases, and we propose that in these cases, substance abuse
      contributed to a faster progression of FXTAS as well as exacerbated white matter
      disease. 

PMID- 25606367
TI  - Parent-delivered touchscreen intervention for children with fragile X syndrome.
AB  - The use of touchscreen applications for the iPad((r)) allows children with
      disabilities to improve their personal autonomy and quality of life. In light of
      this emerging literature and our clinical experience with toddlers and children
      with Fragile X syndrome (FXS), a randomized clinical trial pilot study was
      conducted of whether an interactive iPad((r))-based parent training program was
      efficacious for both individuals with FXS and autism spectrum disorder aged 2-to
      12 compared to wait-listed controls. As a second goal, we assessed the difference
      between direct person-to-person therapy vs. online therapy sessions through
      telehealth. In this case series report it is presented preliminary results of
      four individuals with FXS enrolled in the study and described the innovative
      experience including qualitative and quantitative data analysis. Furthermore, we
      provide professionals with specific guidelines about the use of touchscreen
      devices as in-home learning tools and parent training strategies to actively
      involve families in educational treatments in conjunction with clinical guidance.

PMID- 25606368
TI  - A comparison of psychiatric diagnoses among HIV-infected prisoners receiving
      combination antiretroviral therapy and transitioning to the community.
AB  - BACKGROUND: The criminal justice system (CJS), specifically prisons and jails, is
      ideally suited for uniform screening of psychiatric (PD) and substance use
      disorders (SUDs) among people living with HIV/AIDS (PLWHA), who are concentrated
      in these settings. By accurately diagnosing PDs and SUDs in these controlled
      settings, treatment can be initiated and contribute to improved continuity of
      care upon release. In the context of PLWHA, it may also improve combination
      antiretroviral treatment (cART) adherence, and reduce HIV transmission risk
      behaviors. METHODS: A retrospective data analysis was conducted by creating a
      cohort of PLWHA transitioning to the community from prison or jail enrolled who
      were enrolled in a controlled trial of directly administered antiretroviral
      (DAART). Participants were systematically assessed for PDs and SUDs using the
      Mini International Neuropsychiatric Interview (MINI), a standardized psychiatric
      assessment tool, and compared to diagnoses documented within the correctional
      medical record. RESULTS: Findings confirm a high prevalence of Axis I PDs (47.4%)
      and SUDs (67.1%) in PLWHA even after prolonged abstinence from alcohol and drugs.
      Although prevalence of PDs and SUDs were high in the medical record, there was
      fair to poor agreement among PDs using the MINI, making evident the potential
      benefit of more objective and concurrent PD assessments to guide treatment.
      CONCLUSIONS: Additional PD diagnoses may be detected in PLWHA in CJS using
      supplementary and objective screening tools. By identifying and treating PDs and
      SUDs in the CJS, care may be improved and may ultimately contribute to healthier
      outcomes after community release if patients are effectively transitioned.

PMID- 25606369
TI  - Appearance of leptin-HSP70 correlation, in type 2 diabetes.
AB  - In vitro and in vivo studies have shown conflicting results regarding heat shock
      protein (HSP) and leptin correlation. More importantly both HSP70 and leptin are
      correlated with C reactive proteins. The purpose of the present study was to
      study the correlation between serum HSP70 and leptin levels in patients with type
      2 diabetes stratified according to gender. We performed a cross sectional study
      on the established groups of patients with type 2 diabetes defined as 1: patients
      with long standing diabetes for more than 3 years; and 2: patients with newly
      diagnosed diabetes within recent 6 months who were not on any glucose lowering
      treatment other than by dietary means alone and 3: healthy controls. Patients
      with long standing diabetes had higher HSP70, HbA1c and triglyceride than
      controls. Serum leptin levels were significantly lower in patients with newly
      diagnosed diabetes. Women with type 2 diabetes had higher leptin levels compared
      to men, both before and after treatment. We showed a positive correlation between
      leptin and HSP70 levels in women with type 2 diabetes. The correlation was
      strongest in women with newly diagnosed diabetes (r = 0.59) and was attenuated in
      women who were on treatment (r = 0.3). The significance of this correlation was
      only observed in women with type 2 diabetes. There was no correlation between
      leptin and HSP70 in men. The positive correlation between leptin and HSP is
      observed in chronic inflammation such as type 2 diabetes. It could be
      hypothesized that the observed correlation between serum HSP70 and leptin implies
      a higher state of chronic inflammation. 

PMID- 25606370
TI  - No detectable association of IGF2BP2 and SLC30A8 genes with type 2 diabetes in
      the population of Hyderabad, India.
AB  - Genome-wide association studies identified novel genes associated with T2DM which
      have been replicated in different populations. We try to examine here if certain
      frequently replicated SNPs of Insulin growth factor 2 m-RNA binding protein 2
      (IGF2BP2) (rs4402960, rs1470579) and Solute Carrier family 30 member 8 (SLC30A8)
      (rs13266634) genes, known to be implicated in insulin pathway, are associated
      with T2DM in the population of Hyderabad, which is considered to be a diabetic
      capital of India. Genotyping of the 1379 samples, 758 cases and 621 controls, for
      the SNPs was performed on sequenom massarray platform. The logistic regression
      analysis was done using SPSS software and the post-hoc power of the study was
      estimated using G power. The allele and genotype frequencies were similar between
      cases and controls, both for SNPs of IGF2BP2 and SLC30A8 genes. Logistic
      regression did not reveal significant allelic or genotypic association of any of
      the three SNPs with T2DM. Despite large sample size and adequate power, we could
      not replicate the association of IGF2BP2 and SLC30A8 SNPs with T2DM in our sample
      from Hyderabad (A.P.), India, albeit another study based on much larger sample
      but from heterogeneous populations from the northern parts of India showed
      significant association of two of the above 3 SNPs, suggesting variable nature of
      susceptibility of these genes in different ethnic groups. Although the IGF2BP2
      and SLC30A8 genes are important in the functional pathway of Insulin secretion,
      it appears that these genes do not play a significant role in the susceptibility
      to T2DM in this population. 

PMID- 25606371
TI  - Genetic diversity within 5'upstream region of Toll-like receptor 8 gene reveals
      differentiation of riverine and swamp buffaloes.
AB  - In this study the nucleotide diversity in the 5'untranslated region (UTR) of TLR8
      gene in riverine as well as swamp buffaloes has been described. Analysis of the
      5'UTR of TLR8 gene showed presence of two SNPs in this region, g.-139G>T and g.
      128A>G. A PCR-RFLP assay designed for genotyping of g.-139G>T SNP across 667
      samples from 2 buffalo populations revealed a striking difference in allele
      frequency distribution across the swamp and riverine buffaloes. The frequency of
      T allele was higher in swamp buffalo as compared to riverine buffalo, ranging
      from 0.71 to 1. The G allele on the other hand exhibited a higher frequency
      across all the Indian riverine buffalo breeds/populations. The principal
      component analysis revealed separate clusters for the riverine and swamp
      buffaloes, as expected; however, the riverine type Assamese buffalo population of
      eastern India formed a distinct cluster. Since most of the buffalo populations in
      the eastern region are swamp type, this demarcation may be related to the
      difference in immune response in riverine and swamp buffaloes. These preliminary
      results indicate that the genetic variation observed in 5'upstream region of TLR8
      gene, which differentiates swamp and riverine buffalo, needs to be further
      explored for association with disease susceptibility in buffalo, an important
      dairy and meat animal of Southeast Asia. 

PMID- 25606372
TI  - Mutation study of DsrM from Allochromatium vinosum using the amino acid
      sequences.
AB  - Sulfur metabolism is one of the oldest known environmental processes. The operon
      involved in this process is called the dsr operon. The vital role of the operon
      is to maintain the environmental sulfur balance. The dsr operon of proteobacteria
      consists of 15 genes, viz. dsrABEFHCMKLJOPNRS. The proteins encoded by the dsr
      operon are essential for the transfer of sulfur globules from periplasm to
      cytosol and oxidation of the stored sulfur. In the present study we tried to
      analyze the probable molecular details of the DsrM proteins from a diverse set of
      microbial species using their sequence information. There are certain mutations
      in the sequences of the DsrM proteins from the different proteobacterial species.
      The effects of mutations in the sequences of DsrM proteins were predicted from
      the evolutionary point of view. This is so far the first report of its kind. Our
      study would therefore enable the researches to predict the hitherto unknown
      biochemistry of sulfur oxidation using the amino acid sequences of the DsrM
      proteins. 

PMID- 25606373
TI  - Association between SREBP-1 gene expression in mammary gland and milk fat yield
      in Sarda breed sheep.
AB  - The aim of this study was to examine the expression patterns of SREBP-1 gene in
      milk somatic cells and its association with milk fat yield during early lactation
      in Sarda breed sheep. A sample of 20 Sarda ewes, aged between 4 and 5 years, in
      their third to fourth lactation were chosen. From each ewe 28 days after lambing
      milk yield was measured, and a 160 ml milk sample for the RNA extraction and to
      test somatic cells count and lactose, fat and protein contents were collected.
      From the obtained RNA, total cDNA was synthesized and the quantitative PCR was
      performed. The fat, proteins and lactose content showed many differences among
      the animals, but these variations were no correlated with the milk yield. The
      SREBP-1 gene expression resulted higher in the high milk fat producing ewes. The
      correlation analysis showed that the SREBP-1 expression level is directly related
      to the amount of milk fat (g/die) (P < 0.001), while the total RNA obtained from
      each sample was found to be related to the somatic cells number (P < 0.001).
      Instead the expression of this gene showed no relations with the concentration of
      fat in milk. Our data highlight that in sheep SREBP-1 gene is expressed in the
      mammary gland during early lactation. Moreover, the positive relationship between
      SREBP-1 gene expression and the milk fat yield suggests that SREBP-1 gene is
      required for the lipid synthesis in the sheep mammary gland. 

PMID- 25606374
TI  - Genetic divergence in natural populations of bronze featherback, Notopterus
      notopterus (Osteoglossiformes: Notopteridae) from five Indian rivers, analyzed
      through mtDNA ATPase6/8 regions.
AB  - The present study characterized 842 bp fragment of mitochondrial ATP synthase 6
      and 8 (ATPase6/8) genes in Notopterus notopterus. In all, 97 samples of N.
      notopterus were collected from five distant rivers; viz Satluj, Gomti, Yamuna,
      Brahmaputra and Mahanadi representing 4 river basins in India. The analysis of
      variation revealed presence of 23 haplotypes in ATPase6/8 gene with haplotype
      diversity (Hd) of 0.899 and nucleotide diversity (pi) of 0.00336. The within
      population variation which was 41.78% of the total variation of 58.22% was found
      among population. The Fst value of 0.582 (P < 0.05) of the total population was
      found significant. The results concluded that the polymorphism in ATPase6/8 gene
      is a potential marker that is important for determining genetic divergence of
      wild N. notopterus populations. The findings reveal common ancestry of mahanadi
      population with the populations in rivers of Indo-Gangetic region. However, long
      evolutionary isolation must be responsible for the high genetic divergence
      between N. notopterus in Mahanadi and other regions. 

PMID- 25606375
TI  - The relationship between apolipoprotein CIII gene polymorphism and serum lipid
      levels in Han Chinese males.
AB  - BACKGROUND: Although apolipoprotein (apo) CIII gene polymorphisms have proved to
      be related to the increased serum lipid level in foreign studies, the results
      have not always been consistent among diverse populations. In addition, the
      research focuses on the impact of the apoCIII on the serum lipid levels of Han
      Chinese subjects which was not conducted before. OBJECTIVE: To explore the
      relationship between the apoCIII gene C3175G and T3206G polymorphisms and serum
      lipid levels as well as other risk factors for hyperlipidaemia, in Han Chinese
      males. METHOD: A total of 337 healthy male participants undergoing physical
      examinations were randomly selected from two hospitals in Chongqing, China.
      Through DNA sequencing, apoCIII gene C3175G and T3206G polymorphisms were
      identified and their relationships with serum lipid levels were further analysed.
      RESULTS: Carriers of apoCIII(3175) GG genotypes have higher levels of TG than
      other genotypes (P < 0.05). After the stratified selection of triacylglycerol
      (TG), G gene loci of apoCIIIT3206G are associated with decreasing the content of
      total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) in
      relatively high TG group while the G gene loci of apoCIIIC3175G have an inverse
      effect. The outcome of TG unconditional logistic regression shows that the G gene
      loci of apoCIIIT3206G polymorphism are also beneficial for decreasing TG.
      CONCLUSION: The detection of TG in apoCIII(3175) GG genotype carriers is an
      efficient predictor of hypertriglyceridaemia in Han Chinese males. The G gene
      loci of apoCIII(3206) may be beneficial for decreasing serum lipid level.

PMID- 25606376
TI  - Complete Arabis alpina chloroplast genome sequence and insight into its
      polymorphism.
AB  - The alpine plant Arabis alpina (alpine rock-cress) is a thoroughly studied
      species in the fields of perennial plant flowering regulation, phylogeography,
      and adaptation to harsh alpine climatic conditions. We report the complete A.
      alpina chloroplast genome sequence obtained through de novo assembly of Illumina
      paired-end reads produced by total DNA sequencing. The A. alpina cp circular
      genome is 152,866 bp in length and built of two inverted repeats of 26,933 bp
      separated by unique regions: a large single copy of 82,338 bp and a small single
      copy of 17,938 bp. The genome contains 131 genes, some of them being duplicated
      in the inverted repeats. Seventy-nine unique protein-coding genes were annotated,
      together with 29 tRNA genes and 4 ribosomal RNA genes. Sequencing and mapping of
      23 additional A. alpina DNA samples enabled to gain insight into the intraspecies
      polymorphism of the sequenced cp genome. Genetic variability among genomes was
      detected as 44 indels, most of them being located in noncoding regions, and 130
      single-nucleotide polymorphisms, 37 of them corresponding to mutations in coding
      regions. A. alpina chloroplast genome sequence will be helpful in population
      studies or investigations of chloroplast functions of this alpine plant species. 

PMID- 25606377
TI  - Significance of the use of the ViennaLab "Cardiovascular Disease panel" (CVD)
      Assay as a reflex test for the "Factor V/II/MTHFR Assay".
AB  - INTRODUCTION: Trends toward identifying risk factors of thrombotic complications
      had become essential as an attempt to prevent and decrease the incidence of the
      complications. Thrombosis has been associated with predisposing factors like
      mutations in FV, PTH, MTHFR and other genes. AIM: Evaluate whether the CVD
      StripAssay has an added value in the screening for more thrombophilia risk
      factors, which may predispose for the development of cardiovascular diseases and
      other thrombotic clinical conditions. METHODS: We compared the results for 94
      patients who were previously tested for Factor V, Factor II and MTHFR gene
      mutations using the ViennaLab FV-PTH-MTHFR StripAssay, and for whom additional
      testing for the Cardiovascular Disease panel (CVD StripAssay, ViennaLab) was
      requested. RESULTS: Using the CVD StripAssay, 66% of patients who had no
      mutations when tested using the FV-PTH-MTHFR StripAssay or carried a mutation for
      MTHFR, were found to have additional genes' SNPs or mutations that are highly
      associated with a risk of thrombosis as per the available international
      literature. CONCLUSION: This observation is of extreme importance in clinical
      practice for the introduction of the extended CVD panel into routine molecular
      diagnostic test menus and highlights the importance of genetic analysis of the
      implicated genes in the management of patients with a thrombotic episode
      presentation.

PMID- 25606378
TI  - C-reactive protein + 1059 G>C polymorphism in type 2 diabetes and coronary artery
      disease patients.
AB  - Human C-reactive protein (CRP) is an acute phase reactant involved in chronic and
      acute inflammation. CRP is associated with metabolic syndrome, obesity,
      atherosclerosis, unstable angina, insulin resistance and diabetes. The present
      study evaluates the association of + 1059 G>C silent polymorphism in exon 2 of
      CRP gene in 581 cases [CAD (206), T2D (266), T2D with CAD (109)] and 235 controls
      in the population of Punjab (North-West India). The frequency of + 1059 G allele
      is highest in CAD (98.3%) followed by T2D (98.1%), T2D + CAD cases (97.7%) and
      controls (94.7%). G-allele is associated with increased risk of T2D [P = 0.003,
      OR = 2.93 (1.39-6.17)] and CAD [P = 0.004, OR = 3.25 (1.39-7.60)] in comparison
      to controls. Recessive model shows that GG genotype increases the risk of CAD by
      4 fold (P = 0.003, OR = 4.19, 1.62-10.80), T2D by 3 fold (P = 0.008, OR = 3.23,
      1.36-7.60) and T2D + CAD by 3.5 fold (P = 0.029, OR = 3.64, 1.14-11.66). Factor
      analyses show that BMI, WC, and WHR are core predictors for CAD and T2D, whereas
      CHO, TG and VLDL for T2D + CAD. The present study concludes that GG genotype of
      CRP + 1059 G>C polymorphism and clustering of obesity and dyslipidemia underlie
      the risk towards CAD, T2D and T2D + CAD in the North-West Indian population of
      Punjab. 

PMID- 25606379
TI  - Effect of PON1 gene polymorphisms in Turkish patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: Reactive oxygen species (ROS) can oxidize biological molecules that
      mediate carcinogenesis by causing metabolic malfunction and damage to DNA. Human
      serum paraoxonases (PON1, PON2 and PON3) play a role in antioxidant defense and
      protect the cell against ROS. PON1 polymorphisms Q192R and L55M have been shown
      to be associated with several human cancers, but their association with
      hepatocellular carcinoma (HCC) has yet to be investigated. METHODS: We performed
      genotyping analysis using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 217
      confirmed HCC patients and 217 age-, gender-, smoking- and alcohol consumption
      matched cancer-free controls in Turkish population. RESULTS: Q192R and L55M
      polymorphisms were in significant linkage disequilibrium (LD) (D' = 0.77).
      However, allele, genotype and haplotype analysis showed no significant
      differences between the risks of HCC and PON1 polymorphisms. Moreover, no
      significant differences were found between clinical findings, clinicopathological
      features and sex in comparison with the PON1 genotypes in HCC group. CONCLUSION:
      Our results suggest for the first time that neither the Q192R polymorphism nor
      the L55M polymorphism has relationship with the risk of developing HCC. Further
      independent studies are required to clarify the possible role of PON1 gene Q192R
      and L55M polymorphisms on the risk of developing HCC in a larger series and also
      in patients of different ethnic origins.

PMID- 25606380
TI  - ATRX mutation in two adult brothers with non-specific moderate intellectual
      disability identified by exome sequencing.
AB  - In this report, we describe two adult brothers affected by moderate non-specific
      intellectual disability (ID). They showed minor facial anomalies, not clearly
      ascribable to any specific syndromic patterns, microcephaly, brachydactyly and
      broad toes. Both brothers presented seizures. Karyotype, subtelomeric and FMR1
      analysis were normal in both cases. We performed array-CGH analysis that revealed
      no copy-number variations potentially associated with ID. Subsequent exome
      sequence analysis allowed the identification of the ATRX c.109C>T (p.R37X)
      mutation in both the affected brothers. Sanger sequencing confirmed the presence
      of the mutation in the brothers and showed that the mother is a healthy carrier.
      Mutations in the ATRX gene cause the X-linked alpha thalassemia/mental
      retardation (ATR-X) syndrome (MIM #301040), a severe clinical condition usually
      associated with profound ID, facial dysmorphism and alpha thalassemia. However,
      the syndrome is clinically heterogeneous and some mutations, including the
      c.109C>T, are associated with a broad phenotypic spectrum, with patients
      displaying a less severe phenotype with only mild-moderate ID. In the case
      presented here, exome sequencing provided an effective strategy to achieve the
      molecular diagnosis of ATR-X syndrome, which otherwise would have been difficult
      to consider due to the mild non-specific phenotype and the absence of a family
      history with typical severe cases. 

PMID- 25606381
TI  - Association between 5, 10-methylenetetrahydrofolate reductase (MTHFR)
      polymorphisms and congenital heart disease: A meta-analysis.
AB  - BACKGROUND: Inconsistent results were reported in recent literature regarding the
      association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C
      polymorphisms and the susceptibility of congenital heart disease (CHD). In this
      study, we performed a meta-analysis to investigate the associations by employing
      multiple analytical methods. METHODS: Literature search was performed and
      published articles were obtained from PubMed, Embase and CNKI databases based on
      the exclusion and inclusion criteria. Data were extracted from eligible studies
      and the crude odds ratios and their corresponding 95% confidence intervals (CIs)
      were calculated using random or fix effects model to evaluate the associations
      between the MTHFR C677T/A1298C polymorphisms and CHD development. Subgroup based
      analysis was performed by Hardy-Weinberg equilibrium, ethnicity, types of CHD,
      source of control and sample size. RESULTS: Twenty-four eligible studies were
      included in this meta-analysis. Significant association was found between fetal
      MTHFR C677T polymorphism and CHD development in all genetic models. The pooled
      ORs and 95% CIs in all genetic models indicated that MTHFR C677T polymorphism was
      significantly associated with CHD in Asian, but not Caucasian in subgroup
      analysis. The maternal MTHFR C677T polymorphism was not associated with CHD
      except for recessive model. Moreover, neither maternal nor fetal MTHFR A1298C
      polymorphism was associated with CHD. CONCLUSION: The fetal MTHFR C677T
      polymorphism may increase the susceptibility to CHD. Fetal MTHFR C677T
      polymorphism was more likely to affect Asian fetus than Caucasian. The MTHFR
      A1298C polymorphism may not be a risk of congenital heart disease.

PMID- 25606382
TI  - The association between polymorphism of P53 codon 72 Arg/Pro and hepatocellular
      carcinoma susceptibility: evidence from a meta-analysis of 15 studies with 3704
      cases.
AB  - BACKGROUND: Emerging evidence has shown that p53gene participates in human
      carcinogenesis as tumor suppressors. Polymorphism of p53 gene codon 72 Arg/Pro
      (rs1042522) may influence the function of p53 protein and then affect the
      processing of carcinogenesis. It has been suggested that p53 codon 72 Arg/Pro
      polymorphism is associated with susceptibility to hepatocellular carcinoma (HCC).
      However, published results are inconsistent and inconclusive. To examine the
      validity of the association between the polymorphism and HCC risk, we performed
      this meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: We have conducted a search of
      case-control studies on the associations of p53 codon 72 polymorphism with
      susceptibility to HCC in PubMed, ScienceDirect, Bio-Med central, Springer-link,
      EBSCO, Wanfang databases and Chinese National Knowledge Infrastructure (CNKI)
      databases. A total of 15 studies were identified with 3704 cases and 4559
      controls for codon 72 Arg/Pro polymorphism. The result did support a significant
      genetic association between Pro allele and susceptibility to HCC in all the
      genetic models. Similarly, subgroup analysis showed significant associations
      between the Arg/Pro polymorphism and susceptibility to HCC when stratifying by
      race, gender, source of controls and hepatitis virus infection status.
      CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that p53 codon 72 Arg/Pro
      polymorphism may be associated with the risk of HCC, especially in subgroup
      analysis of Asian and Caucasian population, hospital-based population, the
      female, and the individuals infected with hepatitis virus. However, well-designed
      studies based on different ethnic groups with larger sample size and more
      detailed data are needed to confirm these conclusions.

PMID- 25606383
TI  - Investigation of the monocyte diapedesis-related LFA-1 and JAM-A gene variants in
      Turkish coronary heart disease patients.
AB  - BACKGROUND: LFA-1/JAM-A interaction plays a significant role in early steps of
      leukocyte transendothelial migration (diapedesis) which takes part in
      atherosclerosis pathogenesis. In this population-based case-control study, the
      frequencies of JAM-A rs790056 and LFA-1 rs8058823 gene polymorphisms in patients
      with coronary heart disease (CHD) and healthy subjects were investigated and the
      correlations between the different genotypes and cardiovascular risk factors were
      analyzed. METHODS: The JAM-A and LFA-1 genotypes were determined in 153 patients
      with CHD and 124 controls by PCR-RFLP assay. RESULTS: In CHD patient group, the
      frequency of JAM-A rs790056 TT genotype and the frequency of T allele were higher
      when compared with the control group (p = 0.03 and p = 0.007,respectively). In
      patient groups, the frequency of LFA-1 rs8058823 AA genotype was higher (p =
      0.000), and the frequency of AG genotype was lower when compared with the control
      group (p = 0.031). In the control group, LFA-1 rs8058823 G allele carriers had
      higher SBP than subjects with AA genotype (p = 0.038), whereas in the CHD patient
      group, G allele carriers had lower DBP than subjects with AA genotype (p =
      0.007). The multivariate logistic regression analysis confirmed that the JAM-A
      rs790056 TT genotype (OR = 2.472, p = 0.045) and LFA-1 rs8058823 AA genotype (OR
      = 6.751, p = 0.000) were risk factors for CHD development. CONCLUSION: These
      results suggest that the wild type genotypes and alleles of JAM-A rs790056 (TT
      genotype and T allele) and LFA-1 rs8058823 (AA genotype and A allele) were found
      to be risk factors for CHD, whereas rare genotypes and alleles were found to be
      higher in healthy controls thus being protective.

PMID- 25606384
TI  - A novel insertion-induced frameshift mutation of the androgen receptor gene in a
      patient with primary amenorrhea.
AB  - OBJECTIVE: To report a novel single nucleotide insertion mutation, and present
      the clinical, genetic, biochemical findings in a patient with primary amenorrhea.
      METHODS: Chromosomal analysis was performed by harvesting lymphocytes from
      peripheral blood sample. Hormonal analysis was performed from the serum. After
      genomic DNA extraction from peripheral blood leukocytes the coding regions and
      corresponding exon-intron boundaries of sex-determining region Y (SRY) gene and
      androgen receptor (AR) gene were amplified by PCR and subjected to direct
      sequencing. RESULTS: In the patient with a karyotype 46,XX, we identified a novel
      single nucleotide insertion mutation of the nucleotide G at position 2369
      (GenBank accession number HM010955), resulting in amino acid interchange cysteine
      to tryptophan at codon 669 in exon 4 [Cys669Trp] (GenBank Protein_id ADF47187).
      CONCLUSIONS: We report a novel single nucleotide insertion mutation in exon 4
      region of the AR gene. The nature of the mutation presented in the patient is in
      the ligand-binding domain (LBD) of the AR gene. This insertion mutation was
      predicted to produce frame shift mutation and resulted in truncated form of the
      AR protein, implicating it in the phenotype observed with primary amenorrhea.

PMID- 25606385
TI  - Dental developmental abnormalities in a patient with subtelomeric 7q36 deletion
      syndrome may confirm a novel role for the SHH gene.
AB  - Studies in mice demonstrated that the Shh gene is crucial for normal development
      of both incisors and molars, causing a severe retardation in tooth growth, which
      leads to abnormal placement of the tooth in the jaw and disrupted tooth
      morphogenesis. In humans the SHH gene is located on chromosome 7q36. Defects in
      its protein or signaling pathway may cause holoprosencephaly spectrum, a disorder
      in which the developing forebrain fails to correctly separate into right and left
      hemispheres and that can be manifested in microforms such as single maxillary
      central incisor. A novel role for this gene in the developing human primary
      dentition was recently demonstrated. We report a 12-year old boy with a de novo
      7q36.1-qter deletion characterized by high-resolution karyotyping,
      oligonucleotide aCGH and FISH. His phenotype includes intellectual disability,
      non-verbal communication, hypospadia, partial sacral agenesis and absence of
      coccyx, which are distinctive features of the syndrome and mainly correlated with
      the MNX1, HTR5A and EN2 genes. No microforms of holoprosencephaly spectrum were
      observed; but the patient had diastema and dental developmental abnormalities,
      such as conical, asymmetric and tapered inferior central incisors. The dental
      anomalies are reported herein for the first time in subtelomeric 7q36 deletion
      syndrome and may confirm clinically a novel role for the SHH gene in dental
      development. 

PMID- 25606386
TI  - Identification and expression analysis of a novel intragenic EFNB1 mutation
      causing craniofrontonasal syndrome.
AB  - Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by mutations in
      the EFNB1 gene and characterized by distinctive craniofacial and digital
      malformations. In contrast with most X-linked traits, female patients with CFNS
      display a more severe phenotype than males. In this report, the clinical,
      molecular and RNA expression analyses of a female subject with CFNS are
      described. A novel c.445_449delGAGGG deletion in exon 3 of EFNB1 was demonstrated
      in this patient. To assess the effect of this novel mutation at the transcript
      level, the expression of EFNB1 mRNA was studied by quantitative RT-PCR. To our
      knowledge, this is the first time that an EFNB1 transcript carrying a truncating
      mutation in exon 3 is demonstrated to undergo degradation by nonsense-mediated
      mRNA decay. Our results expand the mutational spectrum of CFNS and add to the
      functional consequences of truncating EFNB1 mutations. 

PMID- 25606387
TI  - Polymorphism analysis and new JAG1 gene mutations of Alagille syndrome in Mexican
      population.
AB  - Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of
      inheritance that affects the liver, heart, eyes, kidneys, skeletal system and
      presents characteristic facial features. Mutations of the JAG1 gene have been
      identified in 20-89% of the patients with Alagille syndrome, this gene encodes
      for a ligand that activates the Notch signaling pathway. In the present study we
      analyzed 9 Mexican patients with Alagille syndrome who presented the clinical
      criteria for the classical presentation of the disease. By using the denaturing
      high performance liquid chromatography mutation analysis we were able to identify
      different mutations in 7 of the patients (77.77%), importantly, we found 5 novel
      mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in
      Mexican population is also reported. The overall results demonstrated an
      expanding mutational spectrum of JAG1 gene in the Mexican population. 

PMID- 25606388
TI  - Current evidence on the four polymorphisms of VDR and breast cancer risk in
      Caucasian women.
AB  - There have been a few epidemiological studies reporting VDR polymorphisms
      including Fok1, Bsm1, Apa1 and Taq1with breast cancer incidence and therefore
      risk. The results however are controversial, often due to smaller sample size.
      Concerning most of the studies were performed on Caucasian women, we conducted
      this comprehensive meta-analysis encompassing 38,151 cases and 47,546 controls
      (Fok1: 13,152 cases, 17,443 controls; Bsm1: 14,755 cases, 18,633 controls; Apa1:
      3080 cases, 3412 controls; Taq1: 7164 cases, 8068 controls) to better understand
      roles of the polymorphisms in breast cancer development among Caucasian
      population. We did not find any association of the most controversial genotype
      Fok1 with breast cancer risk in Caucasian women (ff vs. FF: OR = 1.05, 95% CI =
      0.95-1.22, P = 0.32 for heterogeneity; ff vs. Ff: OR = 1.05, 95% CI = 0.94-1.17,
      P = 0.40; ff vs. Ff + FF: OR = 1.07, 95% CI = 0.95-1.14, P = 0.37 and ff + Ff vs.
      FF: OR = 1.04, 95% CI = 0.99-1.09, P = 0.23). For Bsm1, Apa1 and Taq1, no
      significant association was also not found in the homozygote comparison,
      heterozygote comparison, recessive and dominant models respectively. In
      conclusion, the current analysis suggested that the four polymorphisms (Fok1,
      Bsm1, Apa1 and Taq1) of VDR may be not associated with breast cancer risk in
      Caucasian women. 

PMID- 25606389
TI  - Endothelial nitric oxide synthase (eNOS) 4b/a polymorphism and the risk of
      diabetic nephropathy in type 2 diabetes mellitus: A meta-analysis.
AB  - Many studies have accessed the association between eNOS-4b/a polymorphism and the
      risk of diabetic nephropathy (DN) among type 2 diabetic subjects. However, the
      results are conflicting and inconclusive. The aim of current meta-analysis was to
      more precisely estimate the relationship. Pubmed, Embase, the China National
      Knowledge Infrastructure and the Wanfang Database were searched for articles
      published up to May 26th, 2013 that addressed eNOS-4b/a polymorphism and the risk
      of DN among type 2 diabetic subjects. 18 studies were included in this meta
      analysis. eNOS-4b/a polymorphisms were associated with an overall significantly
      increased risk of DN (allele model: OR = 1.44, 95% CI = 1.14-1.82; additive
      model: OR = 2.03, 95% CI = 1.14-3.62; dominant model: OR = 1.34, 95% CI = 1.07
      1.68; recessive model: OR = 2.01, 95% CI = 1.12-3.61). Subgroup analysis revealed
      a significant association between the eNOS-4b/a polymorphism and DN in Asian
      population, especially in Chinese population, but not in non Asian populations.
      Our meta-analysis supported an association between the 4b/a polymorphism of eNOS
      gene and increased risk of DN in type 2 diabetes among Asians, especially in
      Chinese population. 

PMID- 25606390
TI  - A 20 year history of clinical and genetic study of thyroid autoimmunity in a
      Tunisian multigenerational family: Evidence for gene interaction.
AB  - Autoimmune thyroid diseases (AITD), which include Hashimoto thyroiditis (HT),
      Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized by
      their clinical and genetic heterogeneity. In this study, we have carried on a
      global approach gathering 20 year genetic and clinical data on a Tunisian
      multigenerational family (Akr). Our purpose was search for a combined genotype
      involved in AITD susceptibility using 33 gene polymorphisms. The Akr pedigree is
      composed of more than 400 members distributed on 10 generations. Clinical follow
      up was performed by appreciation of the thyroid gland and measurement of both
      thyroid hormone and auto antibody levels. We used FBAT software to test for
      association between gene polymorphisms and AITDs. Clinical follow-up has showed
      that the number of AITD patients has increased from 25 to 78 subjects subdivided
      on 51 cases of GD, 22 PIM and 5 HT. Concerning genetic analysis, our study has
      revealed new gene association when compared with our previous analysis
      (considering single genes). Thus, PTPN22, TG and VDR gene polymorphisms have
      became associated with p-values ranging from 4.6  10(- 2) to 4  10(- 3) when
      considered with other genes on the same chromosome; giving evidence for gene
      interaction. The most significant association was found with the MHC region (p =
      7.15 10(- 4)). Moreover, and among gene polymorphisms explored, our analysis has
      identified some of them as AITD biomarkers. Indeed, PDS gene polymorphisms were
      associated with either exophthalmia or goiter (p-values from 10(- 2) to 10(- 3)).
      In conclusion, our study gives evidence for gene interaction in AITD development
      confirming genetic complexity of these diseases. 

PMID- 25606391
TI  - Interstitial 12p deletion involving more than 40 genes in a patient with
      postnatal microcephaly, psychomotor delay, optic nerve atrophy, and facial
      dysmorphism.
AB  - Interstitial deletions of chromosome 12p are rare, and the phenotype spectrum is
      therefore still unknown. The thirteen patients reported so far suffer from
      developmental delay, optic nerve hypoplasia, micropenis, hypoplastic hair and
      skin, oligodontia, brachydactyly, and arterial hypertension. We report a de novo
      12p12.2-p11.22 deletion of 9.2 Mb detected by array CGH analysis in a boy with
      global developmental delay, muscular hypotonia, postnatal microcephaly, facial
      dysmorphism including small ears, epicanthus, broad nasal bridge and hypoplastic
      nostrils. In addition, the patient had optic nerve atrophy, inverted nipples,
      micropenis, and a hemangioma. The deleted region encompasses more than 40
      reference genes. We compare phenotype and deletion extent of our index patient to
      that of previous reports and thereby contribute to the understanding of
      interstitial 12p deletion phenotypes. Knowledge of the pattern of this deletion
      phenotype will help clinicians to diagnose this abnormality in their patients and
      to counsel the parents accordingly. Further descriptions may be able to
      contribute to the clarification. 

PMID- 25606392
TI  - Biodiversity of the Betta smaragdina (Teleostei: Perciformes) in the northeast
      region of Thailand as determined by mitochondrial COI and nuclear ITS1 gene
      sequences.
AB  - In Thailand, there are currently five recognized species members of the bubble
      nesting Betta genus, namely Betta splendens, B. smaragdina, B. imbellis, B.
      mahachaiensis and B. siamorientalis. In 2010, we indicated the possibility, based
      on COI barcoding evidence, that there might be two additional species, albeit
      cryptic, related to the type-locality B. smaragdina in some provinces in the
      northeast of Thailand. In the present study, after a more extensive survey of the
      northeast, and phylogenetic analyses based on COI and ITS1 sequences, the B.
      smaragdina group may be composed of at least 3 cryptic species members. The
      phylogenetic positions of these B. smaragdina group members in the bubble-nesting
      bettas' tree together with those of their congeners have been consolidated by
      better DNA sequence quality and phylogenetic analyses. With a better supported
      tree, the species statuses of B. siamorientalis and the Cambodian B. smaragdina
      like fish, B. stiktos, are also confirmed. 

PMID- 25606393
TI  - Marfan syndrome: An eyesight of syndrome.
AB  - Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder
      of connective tissue with prominent manifestations in the skeletal, ocular, and
      cardiovascular systems, is caused by mutations in the glycoprotein gene fibrillin
      1 (FBN1). Aortic root dilation and mitral valve prolapse are the main
      presentations among the cardiovascular malformations of MFS. The revised Ghent
      diagnostics nosology of Marfan syndrome is established in accordance with a
      combination of major and minor clinical manifestations in various organ systems
      and the family history. The pathogenesis of Marfan syndrome has not been fully
      elucidated. However, fibrillin-1 gene mutations are believed to exert a dominant
      negative effect. The treatment includes prophylactic beta-blockers and
      angiotensin II-receptor blockers in order to slow down the dilation of the
      ascending aorta and prophylactic aortic surgery. Importantly, beta-blocker
      therapy may reduce TGF-beta activation, which has been recognized as a
      contributory factor in MFS. The identification of a mutation allows for early
      diagnosis, prognosis, genetic counseling, preventive management of carriers and
      reassurance for unaffected relatives. The importance of knowing in advance the
      location of the putative family mutation is highlighted by its straightforward
      application to prenatal and postnatal screening. The present article aims to
      provide an overview of this rare hereditary disorder. 

PMID- 25606394
TI  - Application of a reliable and rapid polymerase chain reaction based method in the
      diagnosis of myotonic dystrophy type 1 (DM1) in India.
AB  - DM1 is caused by CTG repeat expansion in the 3'-UTR of the DMPK gene. DM1
      patients have expansions of greater than 50 repeats and up to many thousands. The
      intention of the present study is the establishment of reliable and rapid
      polymerase chain reaction methodology in early screening of DM1 patients and
      their family members. PCR followed by TP-PCR was assessed for screening of 27
      cases (from 26 families) and 75 family members and 300 control samples. All
      patients had CTG repeat expansion while forty seven (63%) and twenty eight (37%),
      out of seventy five family members were heterozygous and homozygous respectively.
      Similarly, two hundred thirty (76.77%) and seventy (23.33%), out of three hundred
      control subjects were heterozygous and homozygous respectively and the number of
      repeats varied from 5 to 35. Thirteen complete family screenings were done. Thus,
      TP-PCR is a reliable and rapid molecular technique for the detection of CTG
      repeat expansion in DM1. 

PMID- 25606395
TI  - Isolation and identification of culturable bacteria from honeydew of whitefly,
      Bemisia tabaci (G.) (Hemiptera: Aleyrodidae).
AB  - Bemisia tabaci (G.) is an important pest and a vector of Gemini viruses infecting
      plants. During the process of feeding B. tabaci excretes honeydew which is rich
      in nutrients, and an excellent medium for microbial growth. Recent report proved
      that volatile emitted by the honeydew associated bacteria of aphid, Acyrthosiphon
      pisum Harris was involved in natural enemy calling. Thus understanding the
      honeydew associated bacteria is of paramount importance from the non-chemical
      method of insect pest management. In this perspective, very less information is
      available on bacteria associated with the honeydew excreted by B. tabaci.
      Therefore, in the present study we have isolated and characterized three
      culturable bacteria from the honeydew of B. tabaci viz. Bacillus endophyticus,
      Bacillus niacini and Roseomonas species by employing 16Sr DNA BLASTx analyses
      which revealed that both B. endophyticus and B. niacini had high similarity (>
      99%) to the respective species, while Roseomonas sp. showed only 95% similarity
      to the existing Roseomonas sp. specificity of honeydew association of Roseomonas
      sp. was confirmed by developing specific primers as this genus is reported from
      immunocompromised persons and recently from ticks and mites. The present study
      also indicated the possible host-plant origin of these honeydew associated
      bacteria. 

PMID- 25606396
TI  - Association of interleukin 1 beta (IL-1beta) polymorphism with mRNA expression
      and risk of non small cell lung cancer.
AB  - INTRODUCTION: Interleukin 1 beta (IL- 1beta), a key proinflammatory cytokine
      encoded by the interleukin 1 beta gene, has been associated with chronic
      inflammation and plays an important role in lung inflammatory diseases including
      lung cancer. Elevated levels of Interleukin 1proteins, in particular interleukin
      1 beta greatly enhance the intensity of the inflammatory response. AIM: To study
      the role of interleukin 1 beta-31C > T and -511 T > C polymorphism in the
      pathogenesis of non small cell lung cancer (NSCLC). MATERIALS AND METHODS: One
      hundred and ninety non small cell lung cancer patients and 200 healthy age, sex,
      smoking and dwelling matched controls were used for polymorphic analysis by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      followed by sequencing. Normal tissues of 48 histopathologically confirmed non
      small cell lung cancer patients were taken for mRNA expression analysis.
      Quantitation of interleukin 1 beta was carried out by quantitative real time PCR.
      RESULT: The T/T genotype of interleukin 1 beta-31 gene was significantly
      associated with increased risk of NSCLC [(P = 0.001, OR - 2.8 (95%CI 1.52-5.26)].
      The interleukin 1 beta - 511 T > C does not show any difference between the NSCLC
      and control group (P = 0.3, OR - 0.72 (95%CI 0.41-1.28). Quantitative analysis of
      mRNA showed significant association with interleukin 1 beta T allele as compared
      to the interleukin 1 beta-31C allele (P = 0.006). CONCLUSION: We conclude that
      lung cancer risk genotype interleukin 1 beta-31TT results in increased expression
      of interleukin 1 beta mRNA in lung cancer patients. Our data suggest that this
      genotype (IL1beta -31TT) in the interleukin 1 beta regulatory region provide a
      microenvironment with elevated inflammatory stimuli and thus increasing the risk
      for lung cancer.

PMID- 25606397
TI  - Genetic polymorphism of glutathione S-transferase P1 (GSTP1) in Delhi population
      and comparison with other global populations.
AB  - Glutathione S-transferases (GSTs) belong to a super family of phase II
      detoxification enzymes, which play an important role in protecting cells from
      damage caused by endogenous and exogenous compounds by conjugating reactive
      intermediates with glutathione to produce less reactive water-soluble compounds.
      In the present study, we determined the frequencies of two polymorphisms in exon
      5 and exon 6 of GSTP1 gene in 500 normal individuals from Delhi. GSTP1
      polymorphism was analysed by PCR-RFLP using amplification refractory mutation
      system (ARMS) assay. Two polymorphic sites in GSTP1 (Ile105 -> Val105; Ala114 ->
      Val114) have been analysed simultaneously, which results in four alleles: GSTP1*A
      (wild-type Ile105; Ala114), GSTP1*B (Val105; Ala114), GSTP1*C (Val105; Val114)
      and GSTP1*D (Ile105; Val114). The GSTP1 allele frequency in Delhi population was
      0.663, 0.248, 0.069, and 0.020 for GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D
      respectively. The frequency of Ile105 and Val105 allele was 0.683 and 0.317
      respectively and it was calculated for the purpose of comparison with published
      data where all the four alleles were not analysed. GSTP1 alleles from Delhi
      population were compared with reported frequencies from all over India, and from
      other ethnic groups worldwide. This study would provide a basic database for
      future genetic studies. 

PMID- 25606398
TI  - Uncoupling protein 2 gene polymorphisms in association with overweight and
      obesity susceptibility: A meta-analysis.
AB  - A meta-analysis was performed to evaluate the associations of uncoupling protein
      2 (UCP2) gene polymorphisms (Ala55Val, 45-bp insertion/deletion, and -866G/A)
      with overweight and obesity. A total of 42 studies were included in our analysis.
      Pooled effect estimates and 95% confidential intervals of each polymorphism were
      calculated under different inherited models. Fixed or random effect model was
      selected based on the between-study heterogeneity evaluated with I(2) . Source of
      heterogeneity was explored by subgroup analysis and meta-regression analysis.
      Potential publication bias was assessed using funnel plot and Peters test. After
      excluding studies that deviated from the Hardy-Weinberg equilibrium, T allele of
      Ala55Val polymorphism was associated with an increased risk of overweight and
      obesity under recessive model in the overall (OR = 1.24, 95%CI = 1.06-1.45) and
      Asian (OR = 1.28, 95%CI = 1.06-1.55) populations; and A allele of -866G/A
      polymorphism had a protective effect on overweight and obesity, especially for
      European populations (dominant model: OR = 0.88, 95%CI = 0.81-0.96, co-dominant 1
      model: OR = 0.89, 95%CI = 0.81-0.98, co-dominant 2 model: OR = 0.85, 95%CI = 0.74
      0.94, additive model: OR = 0.88, 95%CI = 0.80-0.95, and allelic model: OR = 0.91,
      95%CI = 0.86-0.97). No evidence was observed in the association of 45-bp
      insertion/deletion polymorphism with overweight and obesity susceptibility. We
      failed to fully explore the between-study heterogeneity regarding the association
      of Ala55Val polymorphism with overweight and obesity. Further studies are
      required to provide more convincing evidence. 

PMID- 25606399
TI  - Is microcephaly a so-far unrecognized feature of XYY syndrome?
AB  - *47,XYY syndrome is a frequent sex chromosome aneuploidy.*Overview of
      characteristic symptoms of 47,XXY*First report of 47,XYY and microcephaly in a
      preterm child*Brief differential diagnosis of microcephaly. 

PMID- 25606400
TI  - Genetic analysis of axial length genes in high grade myopia from Indian
      population.
AB  - PURPOSE: To study the putative association of Membrane frizzled related protein
      (MFRP) and Visual system homeobox protein (VSX2) gene variants with axial length
      (AL) in myopia. METHOD: A total of 189 samples with (N = 98) and without (N = 91)
      myopia were genotyped for the MRFP and VSX2 variations in ABI Prism 3100 AVANT
      genetic analyzer. Genotype/haplotype analysis was performed using PLINK,
      Haploview and THESIAS softwares. RESULTS: Fifteen variations were observed in the
      MFRP gene of which, rs36015759 (c.492C > T, T164T) in exon 5 was distributed at a
      high frequency in the controls and significantly associated with a low risk for
      myopia (P = 4.10 * e(- 07) OR < 1.0). An increased frequency for the coding
      haplotype block [CGTCGG] harboring rs36015759 was observed in controls (31%) than
      cases (8%) that also correlated with a decreased mean AL (- 1.35085; P =
      0.000444) by THESIAS analysis. The 'T' allele of rs36015759 was predicted to
      abolish the binding site for splicing enhancer (SRp40) by FASTSNP analysis.
      CONCLUSION: Myopia is a complex disorder influenced by genetic and environmental
      factors. Our work shows evidence of association of a specific MFRP haplotype
      which was more prevalent in controls with decreased AL. However, replication and
      functional studies are warranted to confirm these findings.

PMID- 25606401
TI  - The great diversity of major histocompatibility complex class II genes in
      Philippine native cattle.
AB  - Bovine leukocyte antigens (BoLA) are extensively used as markers for bovine
      disease and immunological traits. However, none of the BoLA genes in Southeast
      Asian breeds have been characterized by polymerase chain reaction (PCR)-sequence
      based typing (SBT). Therefore, we sequenced exon 2 of the BoLA class II DRB3 gene
      from 1120 individual cows belonging to the Holstein, Sahiwal, Simbrah, Jersey,
      Brahman, and Philippine native breeds using PCR-SBT. Several cross-breeds were
      also examined. BoLA-DRB3 PCR-SBT identified 78 previously reported alleles and
      five novel alleles. The number of BoLA-DRB3 alleles identified in each breed from
      the Philippines was higher (71 in Philippine native cattle, 58 in Brahman, 46 in
      Holstein * Sahiwal, and 57 in Philippine native * Brahman) than that identified
      in breeds from other countries (e.g., 23 alleles in Japanese Black and 35 in
      Bolivian Yacumeno cattle). A phylogenetic tree based on the DA distance
      calculated from the BoLA-DRB3 allele frequency showed that Philippine native
      cattle from different Philippine islands are closely related, and all of them are
      closely similar to Philippine Brahman cattle but not to native Japanese and Latin
      American breeds. Furthermore, the BoLA-DRB3 allele frequency in Philippine native
      cattle from Luzon Island, located in the Northern Philippines was different from
      that in cattle from Iloilo, Bohol, and Leyte Islands, which are located in the
      Southern Philippines. Therefore, we conclude that Philippine native cattle can be
      divided into two populations, North and South areas. Moreover, a neutrality test
      revealed that Philippine native cattle from Leyte showed significantly greater
      genetic diversity, which may be maintained by balancing selection. This study
      shows that Asian breeds have high levels of BoLA-DRB3 polymorphism. This finding,
      especially the identification of five novel BoLA-DRB3 alleles, will be helpful
      for future SBT studies of BoLA-DRB3 alleles in East Asian cattle. 

PMID- 25606402
TI  - Study of rumen metagenome community using qPCR under different diets.
AB  - The aim of this study was to detect the major bacteria present in rumen
      microbiota. Here, we performed qPCR based absolute quantitation of selected rumen
      microbes in rumen fluid of river buffalo adapted to varying proportion of
      concentrate to roughage diets. Animals were adapted to roughage-to-concentrate
      ratio in the proportion of 100:00 (T1), 75:25 (T2), 50:50 (T3) and 25:75 (T4)
      respectively for 30 days. At the end of each treatment, rumen fluid was collected
      at 0 h and 2 h after feeding. It was found that among fibrolytic bacteria
      Ruminococcus flavefaciens (2.22 * 10(8) copies/ml) were highest in T2 group and
      followed by 1.11 * 10(8) copies/ml for Fibrobacter succinogenes (T2), 2.56 *
      10(7) copies/ml for Prevotella ruminicola (T1) and 1.25 * 10(7) copies/ml for
      Ruminococcus albus (T4). In non-fibrolytic bacteria, the Selenomonas ruminantium
      (2.62 * 10(7) copies/ml) was predominant in group T3 and followed by Treponema
      bryantii (2.52 * 10(7)copies/ml) in group T1, Ruminobacter amylophilus (1.31 *
      10(7)copies/ml) in group T1 and Anaerovibrio lipolytica (2.58 * 10(6) copies/ml)
      in group T4. It is most notable that R. flavefaciens were the highest in
      population in the rumen of Surti buffalo fed wheat straw as roughage source. 

PMID- 25606403
TI  - The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a
      nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation
      genetic diagnosis.
AB  - Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder
      caused by mutations in the HEXA gene resulting in beta-hexosaminidase A (HEX A)
      deficiency and neuronal accumulation of GM2 ganglioside. We describe the first
      patient with Tay-Sachs disease in the Cypriot population, a juvenile case which
      presented with developmental regression at the age of five. The diagnosis was
      confirmed by measurement of HEXA activity in plasma, peripheral leucocytes and
      fibroblasts. Sequencing the HEXA gene resulted in the identification of two
      previously described mutations: the nonsense mutation c.78G>A (p.Trp26X) and the
      silent mutation c.1305C>T (p.=). The silent mutation was reported once before in
      a juvenile TSD patient of West Indian origin with an unusually mild phenotype.
      The presence of this mutation in another juvenile TSD patient provides further
      evidence that it is a disease-causing mutation. Successful preimplantation
      genetic diagnosis (PGD) and prenatal follow-up were provided to the couple. 

PMID- 25606404
TI  - Bovine NR1I3 gene polymorphisms and its association with feed efficiency traits
      in Nellore cattle.
AB  - The Nuclear receptor 1 family I member 3 (NR1I3), also known as the Constitutive
      Androstane Receptor (CAR), was initially characterized as a key regulator of
      xenobiotic metabolism. However, recent biochemical and structural data suggest
      that NR1I3 is activated in response to metabolic and nutritional stress in a
      ligand-independent manner. Thus, we prospected the Bovine NR1I3 gene for
      polymorphisms and studied their association with feed efficiency traits in
      Nellore cattle. First, 155 purebred Nellore bulls were individually measured for
      Residual Feed Intake (RFI) and the 25 best (High Feed Efficiency group, HFE) and
      the 25 worst animals (Low Feed Efficiency group, LFE) were selected for DNA
      extraction. The entire Bovine NR1I3 gene was amplified and polymorphisms were
      identified by sequencing. Then, one SNP different between HFE and LFE groups was
      genotyped in all the 155 animals and in another 288 animals totalizing 443
      Nellore bulls genotyped for association of NR1I3 SNPs with feed efficiency
      traits. We found 24 SNPs in the NR1I3 gene and choose a statistically different
      SNP between HFE and LFE groups for further analysis. Genotyping of the 155
      animals showed a significant association within SNP and RFI (p = 0.04), Residual
      Intake and BW Gain (p = 0.04) and Dry Matter Intake (p = 0.01). This SNP is
      located in the 5'flanking promoter region of NR1I3 gene and different alleles
      alter the binding site for predicted transcriptional factors as HNF4alpha, CREM
      and c-MYB, leading us to conclude that NR1I3 expression and regulation might be
      important to feed efficiency. 

PMID- 25606405
TI  - The complete mitochondrial genome of Aspiorhynchus laticeps and its phylogenetic
      analysis.
AB  - The complete nucleotide sequence of the mitochondrial genome (mitogenome) of
      Aspiorhynchus laticeps was determined. The length of the complete mitochondrial
      DNA sequence of A. laticeps is 16,591 bp, which consists of 13 protein-coding
      genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a non
      coding region 'D-loop'. Except for the D-loop, another non-coding region named
      replication origin of L-strand (OL) region was also found. According to the
      phylogenetic analysis, A. laticeps has a closer relationship with Schizothorax. 

PMID- 25606406
TI  - Genetic polymorphisms in miRNAs targeting the estrogen receptor and their effect
      on breast cancer risk.
AB  - Breast cancer is the cancer that most commonly affects women worldwide. This type
      of cancer is genetically complex, but is strongly linked to steroid hormone
      signaling systems. Because microRNAs act as translational regulators of multiple
      genes, including the steroid nuclear receptors, single nucleotide polymorphisms
      (SNPs) in microRNA genes can have potentially wide-ranging influences on breast
      cancer development. Thus, this study was conducted to investigate the
      relationships between six SNPs (rs6977848, rs199981120, rs185641358, rs113054794,
      rs66461782, and rs12940701) located in four miRNA genes predicted to target the
      estrogen receptor (miR-148a, miR-221, miR-186, and miR-152) and breast cancer
      risk in Caucasian Australian women. By using high resolution melt analysis (HRM)
      and polymerase chain reaction- restriction fragment length polymorphism (PCR
      RFLP), 487 samples including 225 controls and 262 cases were genotyped. Analysis
      of their genotype and allele frequencies indicated that the differences between
      case and control populations were not significant for rs6977848, rs66461782, and
      rs12940701 because their p-values are 0.81, 0.93, and 0.1, respectively, which
      are all above the threshold value (p = 0.05). Our data thus suggests that these
      SNPs do not affect breast cancer risk in the tested population. In addition,
      rs199981120, rs185641358, and rs113054794 could not be found in this population,
      suggesting that these SNPs do not occur in Caucasian Australians. 

PMID- 25606407
TI  - Genetic diversity and phylogenetic analysis of Citrus (L) from north-east India
      as revealed by meiosis, and molecular analysis of internal transcribed spacer
      region of rDNA.
AB  - The north-eastern region of India is reported to be the center of origin and rich
      in diversity of Citrus (L.) species, where some wild and endangered species
      namely Citrus indica, Citrus macroptera, Citrus latipes, Citrus ichagensis and
      Citrus assamensis exist in their natural and undisturbed habitat. In order to
      have comprehensive information about the extent of genetic variability and the
      occurrence of cryptic genomic hybridity between and within various Citrus
      species, a combined approach involving morphological, cytogenetical and molecular
      approaches were adopted in the present study. Cytogenetic approaches are known to
      resolve taxonomic riddles in a more efficient manner, by clearly delineating taxa
      at species and sub species levels. Male meiotic studies revealed a gametic
      chromosome number of n = 9, without any evidence of numerical variations.
      Bivalents outnumbered all other types of associations in pollen mother cells
      (PMCs) analyzed at diplotene, diakinesis and metaphase I. Univalents were
      frequently encountered in nine species presently studied, though their presence
      appropriately did not influence the distributional pattern of the chromosomes at
      anaphases I and II. The molecular approaches for phylogenetic analysis based on
      sequence data related to ITS 1, ITS 2 and ITS 1 + 5.8 s + ITS 2 of rDNA using
      maximum parsimony method and Bayesian inference have thrown light on species
      inter-relationship and evolution of Citrus species confirming our cytogenetical
      interpretations. The three true basic species i.e. Citrus medica, Citrus maxima
      and Citrus reticulata with their unique status have been resolved into distinct
      clades with molecular approaches as well. C. indica which occupies a unique
      position in the phylogenetic ladder of the genus Citrus has been resolved as a
      distinct clade and almost behaving as an out-group. The presences of
      quadrivalents in C. indica also echo and support its unique position. From our
      study it is amply clear that C. reticulata also has close relation to C.
      ichagensis, as these species have clustered together, denoting their close
      genetic relationship. On the other hand, our studies did not demonstrate a clear
      differentiation between subgenera Citrus and Papeda at the rDNA level. The
      combined approach of cytogenetical and molecular analysis did complement our
      early karyological findings and helped in resolving many a taxonomic riddles. 

PMID- 25606408
TI  - Metagenomic analysis of buffalo rumen microbiome: Effect of roughage diet on
      Dormancy and Sporulation genes.
AB  - Buffalo rumen microbiome experiences a variety of diet stress and represents
      reservoir of Dormancy and Sporulation genes. However, the information on genomic
      responses to such conditions is very limited. The Ion Torrent PGM next generation
      sequencing technology was used to characterize general microbial diversity and
      the repertoire of microbial genes present, including genes associated with
      Dormancy and Sporulation in Mehsani buffalo rumen metagenome. The research
      findings revealed the abundance of bacteria at the domain level and presence of
      Dormancy and Sporulation genes which were predominantly associated with the
      Clostridia and Bacilli taxa belonging to the phyla Firmicutes. Genes associated
      with Sporulation cluster and Sporulation orphans were increased from 50% to 100%
      roughage treatment, thereby promoting sporulation all along the treatments. The
      spore germination is observed to be the highest in the 75% roughage treatment
      both in the liquid and solid rumen fraction samples with respect to the decrease
      in the values of the genes associated with spore core dehydration, thereby
      facilitating spore core hydration which is necessary for spore germination. 

PMID- 25606409
TI  - mtDNA G10398A variation provides risk to type 2 diabetes in population group from
      the Jammu region of India.
AB  - Mitochondrion plays an integral role in glucose metabolism and insulin secretion.
      Mitochondrial electron-transport chain (ETC) is involved in adenosine
      triphosphate (ATP) generation and ATP mediated insulin secretion in pancreatic
      beta-cells. beta-cell dysfunction is a critical component in the pathogenesis of
      type 2 diabetes (T2D). The mtDNA G10398A variation (amino acid change: Alanine ->
      Threonine) within the NADH dehydrogenase (ND3) subunit of complex I of mtDNA ETC,
      has emerged as a variation of clinical significance in various disorders
      including T2D. This variation is supposed to result in altered complex I
      function, leading to an increased rate of electron leakage and reactive oxygen
      species (ROS) production, which might cause beta-cell damage and impaired insulin
      secretion. The aim of the study was to explore the association of mtDNA G10398A
      variation with T2D in a total of 439 samples (196 T2D cases and 243 healthy
      controls) belonging to the Jammu region of Jammu and Kashmir (J&K). The candidate
      gene association analyses showed significant association of mtDNA G10398A variant
      with T2D and the estimated odds ratio (OR) was 2.83 (1.64-4.90 at 95% CI) in the
      studied population group. The extent of genetic heterogeneity in T2D and
      diversity of the Indian population groups, make such replication studies
      pertinent to understand the etiology of T2D in these population groups. 

PMID- 25606410
TI  - De novo 393 kb microdeletion of 7p11.2 characterized by aCGH in a boy with
      psychomotor retardation and dysmorphic features.
AB  - We report on a 27 month old boy presenting with psychomotor delay and dysmorphic
      features, mainly mild facial asymmetry, prominent cup-shaped ears, long
      eyelashes, open mouth appearance and slight abnormalities of the hands and feet.
      Array comparative genomic hybridization revealed a 393 kb microdeletion in
      7p11.2. We discuss the possible involvement of CHCHD2, GBAS, MRPS17, SEPT14 and
      PSPH on our patient's phenotype. Additionally, we studied the expression of two
      other genes deleted in the patient, CCT6A and SUMF2, for which there is scarce
      data in the literature. Based on current knowledge and the de novo occurrence of
      this finding in our proband we presume that the aberration is likely to be
      pathogenic in our case. However, a single gene disorder, elsewhere in the genome
      or in this very region cannot be ruled out. Further elucidation of the properties
      of this chromosomal region, as well as of the role of the genes involved will be
      needed in order to draw safe conclusions regarding the association of the
      chromosomal deletion with the patient's features. 

PMID- 25606411
TI  - PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071)
      genetic diversity in Latvians, Lithuanians and Taiwanese.
AB  - PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071)
      genetic diversity was investigated in 1438 unrelated subjects from Latvia,
      Lithuania and Taiwan. In general, polymorphism of each individual locus showed
      tendencies similar to determined previously in HapMap populations. Main
      differences concern Taiwanese and include presence of rs2277460 rare allele A not
      found before in Asians and absence of rs2295827 rare alleles homozygotes TT
      observed in all other human populations. Observed patterns of SNPs and haplotype
      diversity were compatible with expectation of neutral model of evolution. Linkage
      disequilibrium between the rs2295826 and rs2295827 was detected to be complete in
      Latvians and Lithuanians (D' = 1; r(2) = 1) and slightly disrupted in Taiwanese
      (D' = 0.978; r(2) = 0.901). Population differentiation (FST statistics) was
      estimated from pairwise population comparisons of loci variability, five locus
      haplotypes and PSMA6 and PSMC6 two locus haplotypes. Latvians were significantly
      different from all Asians at each of 5 SNPs and from Lithuanians at the rs1048990
      and PSMC6 loci. Lithuanian and Asian populations exhibited similarities at the
      PSMC6 loci and were different at the PSMA6 and PSMA3 SNPs. Considering five locus
      haplotypes all European populations were significantly different from Asian;
      Lithuanian population was different from both Latvian and CEU. Allele specific
      patterns of transcription factor binding sites and splicing signals were
      predicted in silico and addressed to eventual functionality of nucleotide
      substitutions and their potential to be involved in human genome evolution and
      geographical adaptation. Current study represents a novel step toward a
      systematic analysis of the proteasomal gene genetic diversity in human
      populations. 

PMID- 25606412
TI  - Investigation of Calpain 10 (rs2975760) gene polymorphism in Asian Indians with
      Gestational Diabetes Mellitus.
AB  - BACKGROUND: Type 2 Diabetes Mellitus (T2DM) and Gestational Diabetes Mellitus
      (GDM) are part of a heterogeneous and complex metabolic group of disorders that
      share common pathophysiological circumstances, including beta-cell dysfunction
      and insulin resistance. The protein Calpain 10 (CAPN10) plays a role in glucose
      metabolism, pancreatic beta-cell insulin secretion, and thermogenesis. OBJECTIVE:
      Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP)
      based genotyping of CAPN10 (rs2975760) polymorphism was carried out in T2DM and
      GDM with suitable controls for each of the pathologies from the same population.
      Genomic DNA was isolated from 787 participants, including 250 cases of T2DM, 287
      pregnant women, of which 137 were identified as having GDM and the remaining 150
      were confirmed as non-GDM, and 250 healthy control volunteers, and association
      analysis was carried out for genotypes and alleles. RESULTS: In the present
      study, T2DM was compared with healthy controls and was not found to be associated
      with the CAPN10 C allele (odds ratio, OR: 1.09; 95% CI = 0.8011-1.484; p =
      0.5821). GDM also did not show any association when compared with non-GDM (OR:
      1.124; 95% CI = 0.7585-1.667; p = 0.5606) respectively. CONCLUSION: Our study
      suggests that the CAPN10 (rs2975760) polymorphism scrutinized in this study is
      not associated with T2DM and GDM.

PMID- 25606413
TI  - Polymorphism of FABP2 and PPARG2 genes in risk prediction of cataract among North
      Indian population.
AB  - BACKGROUND: Cataract is the leading cause of bilateral blindness in India. It has
      been reported that cataract is responsible for 50-80% of the bilaterally blind in
      the country. Cataract formation is a natural part of the ageing process. At
      present, adequate data are not available regarding the FABP2 and PPARG2 gene
      polymorphisms and their susceptibility with cataract cases in the North Indian
      population. Thus, the present study was carried out to investigate the
      association of FABP2 and PPARG2 gene polymorphisms with cataract cases and
      controls. MATERIALS AND METHODS: This study includes 130 cataract cases and 118
      controls. FABP2 and PPARG2 gene polymorphisms in cases and controls were
      evaluated by PCR-RFLP. RESULTS: Frequencies of Ala54Ala, Ala54Thr and Thr54Thr
      genotypes in FABP2 gene in cataract cases and controls were 50.76%, 39.23%, 10%
      and 25.42%, 61.86%, 12.71% respectively. The PPARG2 gene CC, CG, GG genotype
      frequencies were 11.53%, 87.69% and 0.76% in cases and 21.18%, 39.83% and 38.98%
      in healthy controls respectively. Significant differences were observed in the
      frequencies of FABP2 Ala54Ala, Ala54Thr genotype (p < 0.05) and PPARG2 CC, CG, GG
      genotype (p < 0.05) between cases and controls. CONCLUSION: The findings of this
      study suggest that FABP2 and PPARG2 gene polymorphisms can be an informative
      marker for early identification of population at risk of cataract. The potential
      role of FABP2 and PPARG2 gene polymorphisms as a marker of susceptibility to
      cataract needs further studies in a larger number of patients.

PMID- 25606414
TI  - ABCB1 C3435T and CYP2C19*2 polymorphisms in a Palestinian and Turkish population:
      A pharmacogenetic perspective to clopidogrel.
AB  - Clopidogrel is an antiplatelet drug used to prevent recurrent ischemic events
      after acute coronary syndrome and/or coronary stent implantation. Single
      nucleotide polymorphisms (SNPs) such as CYP2C19*2 and ABCB1 C3435T have been
      found to play a role in different individual responses to clopidogrel. Since the
      prevalence of these SNPs is generally known to differ from one population to
      another, the aim of this study was to examine their prevalence in both a
      Palestinian and Turkish population. One hundred unrelated Palestinian subjects
      and 100 unrelated Turkish subjects were analyzed for CYP2C19*2 and ABCB1 C3435T
      polymorphisms by the amplification refractory mutation system (ARMS). Results
      showed an ABCB1 3435 T allele frequency of 0.46 (95% CI 0.391 to 0.529) in the
      Palestinian sample and 0.535 (95% CI 0.4664 to 0.6036) in the Turkish sample.
      CYP2C19*2 allele frequency was 0.095 (95% CI 0.0558 to 0.134) in the Palestinian
      sample and 0.135 (95% CI 0.088 to 0.182) in the Turkish sample. Our results
      provide information about the prevalence of the polymorphisms related to
      clopidogrel response in both the Palestinian and Turkish populations, in order to
      improve the safety and efficacy of clopidogrel through use of genetically guided,
      individualized treatment. The prevalence of these clinically significant alleles
      shed light on the importance of testing them before prescribing clopidogrel. 

PMID- 25606415
TI  - A new gene in A. rubens: A sea star Ig kappa gene.
AB  - The sea star Asterias rubens reacts specifically to the antigen:HRP (horse-radish
      peroxydase) and produces an antibody anti-HRP. We previously identified a
      candidate Ig kappa gene corresponding to this manuscript. We show now the gene
      referred to as: "sea star Ig kappa gene in its specificity". 

PMID- 25606416
TI  - CHP2 gene expression and quantitation in Egyptian patients with acute leukemia.
AB  - AIM: CHP2 (calcineurin B homologous protein 2) is identified as a tumor
      associated antigen highly expressed in different malignancies. It plays a
      critical role in cancer cell development, proliferation, motility and survival.
      It is suggested that the human tumor related gene CHP2 expression in leukemia
      primary cells and leukemia cell lines significantly increase, which may play an
      important role in growth process of leukemia cells. METHODS: In this study, the
      expression of CHP2 gene was analyzed in 10 normal healthy controls and 40
      patients with de novo acute leukemia (20 AML and 20 ALL). CHP2 expression was
      analyzed using a real-time quantitative reverse-transcriptase polymerase chain
      reaction (RTQ-PCR) to investigate a possible relation, association or correlation
      with the clinical features of AL (acute leukemia) at diagnosis, such as age,
      gender, lineage, HB, TLC, platelet count, BM blast cell infiltration and risk
      group. RESULTS: CHP2 was highly expressed in 13/40 AL studied patients (7/20 AML
      and 6/20 ALL) with mean expression level of 2.7 while it was not expressed in any
      of the controls. CONCLUSIONS: Many studies suggest that CHP2 expression is a
      novel prognostic marker in AL and thus needs to be incorporated into the patient
      stratification and treatment protocols. In addition, a quarter of AL patients
      fail therapy and novel treatments that are focused on undermining specifically
      the leukemic process are needed urgently.

PMID- 25606417
TI  - Association of the rs11196218 polymorphism in TCF7L2 with type 2 diabetes
      mellitus in Asian population.
AB  - OBJECTIVE: To clarify the association of rs11196218 polymorphism in transcription
      factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in Asian population
      by a case-control study and meta-analysis. METHODS: In the case-control study,
      1842 patients with T2DM and 7777 normal glucose-tolerant controls in the Henan
      province of China were genotyped for rs11196218 in TCF7L2 by PCR-ligase detection
      reaction. We used allele, co-dominant, dominant and recessive models to evaluate
      the risk association and performed a meta-analysis of the results of different
      genetic models in previous studies and the current study. RESULTS: The AG
      genotype of rs11196218 was associated with risk of T2DM in the Henan population
      (odds ratio 1.37, 95% confidence interval 1.06-1.78), and dominant model showed
      marginal significant association (1.28, 0.99-1.67). Meta-analysis of 10 studies
      revealed the dominant model associated with T2DM in the overall population (1.20,
      1.05-1.36). When stratified by region (southern and northern China and Japan),
      both the AG genotype and the dominant model were associated with risk of T2DM in
      southern Chinese (1.31, 1.03-1.66; 1.27, 1.01-1.60, respectively). CONCLUSION:
      The rs11196218 polymorphism in TCF7L2 is associated with risk of T2DM in Asian
      population.

PMID- 25606418
TI  - A novel mutation of CLCNKB in a Japanese patient of Gitelman-like phenotype with
      diuretic insensitivity to thiazide administration.
AB  - The clinical phenotypes of patients with Bartter syndrome type III sometimes
      closely resemble those of Gitelman syndrome. We report a patient with mild, adult
      onset symptoms, such as muscular weakness and fatigue, who showed hypokalemic
      metabolic alkalosis, elevated renin-aldosterone levels with normal blood
      pressure, hypocalciuria and hypomagnesemia. She was also suffering from
      chondrocalcinosis. A diuretic test with furosemide and thiazide showed a good
      response to furosemide, but little response to thiazide. Although the clinical
      findings and diuretic tests predicted that the patient had Gitelman syndrome,
      genetic analysis found no mutation in SLC12A3. However, a novel missense
      mutation, p.L647F in CLCNKB, which is located in the CBS domain at the C-terminus
      of ClC-Kb, was discovered. Therefore, gene analyses of CLCNKB and SLC12A3 might
      be necessary to elucidate the precise etiology of the salt-losing tubulopathies
      regardless of the results of diuretic tests. 

PMID- 25606419
TI  - G894T endothelial nitric oxide synthase polymorphism and ischemic stroke in
      Morocco.
AB  - Nitric oxide plays a major role in the regulation of cerebral blood flow and loss
      of its function leads to alteration of the vascular relaxation given its central
      role in the physiology of the vascular system. G894T eNOS polymorphism could have
      adverse effects on the expression and activity of endothelial nitric oxide
      synthase, which can result in functional impairment of the endothelium and
      contribute to the development of ischemic stroke in the different models of
      transmission. In this study, genotyping with PCR-RFLP and HRM (high resolution
      melting) methods were conducted on 165 ischemic stroke patients as well as 182
      controls. The goal here was to compare genotyping with PCR-RLFP primer sequences
      of eNOS gene (size < 300 bp) to HRM. Our data suggests a statistically
      significant association between G894T eNOS polymorphism and ischemic stroke in
      recessive, dominant and additive models with P < 0.05 and odds ratio of 2.68
      (1.08-6.70), 1.78 (1.16-2.73), and 1.71 (1.21-2.43) respectively. In sum,
      although the sample size is relatively small, it suggests that G894T eNOS
      polymorphism could be a potentially important genetic marker of ischemic stroke
      in the Moroccan population. Future studies should be conducted in this direction
      taking into consideration the functional activity of eNOS. 

PMID- 25606420
TI  - Distribution of CYP17alpha polymorphism and selected physiochemical factors of
      uterine leiomyoma in Barbados.
AB  - Uterine leiomyoma is a major reproductive health disease among women and in
      particular Black women. The present study sought to determine whether a single
      nucleotide polymorphism (SNP) of CYP17 (rs743572) was associated with the risk of
      developing uterine leiomyoma (UL) in affected women in Barbados; a majority Black
      population. It also sought to determine if BMI, waist circumference and
      oestradiol levels were associated with UL in this group. A total of 96 random
      persons were assessed in a case-control study using a PCR-RFLP assay, and
      measurements of body mass index, waist circumference, and oestradiol levels were
      also assessed. Our results showed no genetic association with the risk of UL and
      this gene. The genetic distribution of CYP 17alpha- alleles resembled a normal
      Hardy-Weinberg distribution, and a relatively low risk of 0.25 at a confidence
      interval at 95%, of UL disease development. However, a significant association
      was found between oestradiol levels and fibroids, as well as oestradiol levels
      and BMI, at P < 0.05 among cases. Therefore our study indicates that significant
      associations between physiochemical factors comprising BMI, waist circumference,
      and oestrogen levels are disease indicators in this population. In conclusion,
      our findings suggest that obesity and its associated risk factors are important
      in a majority Black Caribbean population, although the sample size needs to be
      increased. 

PMID- 25606421
TI  - Evaluating the association of APOA2 polymorphism with insulin resistance in
      adolescents.
AB  - BACKGROUND: 265T>C SNP in the APOA-II gene promoter may be associated with
      obesity risk and insulin resistance (IR). This study aims to analyze the
      association between the APOA2 - 265T>C SNP and risk for obesity and IR in
      adolescents. MATERIAL AND METHODS: The study was conducted on 500 adolescents.
      They were 240 obese and 260 non-obese individuals, aged 16-21 years old. Their
      mean age was 18.25 +/- 2.54 years. Variables examined body weight, height, waist
      circumference (WC), systolic and diastolic blood pressure (BP), body fat
      percentage (BF%), and abdominal visceral fat layer. Homeostasis Model Assessment
      of Insulin Resistance (HOMA-IR) was used as a biomarker for IR. BF% was assessed
      by body composition analyzer and abdominal visceral fat thickness was determined
      by ultrasonography. The APOA2 - 265T>C polymorphism genotype was analyzed by PCR
      amplification of a 273-bp fragment. RESULTS: Genotype frequencies were in Hardy
      Weinberg equilibrium. The frequency of the mutant C allele was significantly
      higher in obese cases than non-obese cases. After multivariate adjustment, waist,
      BF%, visceral adipose layer and HOMA-IR were significantly higher in homozygous
      allele CC carriers than TT + TC carriers. Homozygous individuals for the CC
      allele had statistically higher values of energy intake, total fat (g/day) and
      saturated fat (SATFAT) than carriers of the T allele. CONCLUSIONS: Homozygous
      individuals for the C allele had higher obesity risk than carriers of the T
      allele and had elevated levels of visceral adipose tissue. Moreover, the present
      study shows that the CC polymorphism is associated with the development of IR [OR
      1.89 (1.35-2.91), P = .012] and remains significant after adjusting for gender,
      age and body mass index.

PMID- 25606422
TI  - Keratin 13 mutations associated with oral white sponge nevus in two Chinese
      families.
AB  - White sponge nevus (WSN) is an autosomal dominant hereditary disease. Keratin 4
      (KRT4) and Keratin 13 (KRT13) gene mutations were involved in the WSN. We
      recruited two WSN Chinese families, and oral lesion biopsy with hematoxylin and
      eosin staining showed that patients had significant pathological characteristics.
      The mutations of KRT4 and KRT13 gene were detected by PCR and direct sequencing.
      The multiple alignments of KRT13 from 23 diverse species homology analyses were
      performed by the ClustalW program. The KRT13 expression was measured by Real-Time
      RT-PCR and Western blot analysis. Sequencing analysis revealed two mutations of
      KRT13 gene: one mutation was 332T>C and amino acid change was Leu111Pro. Another
      mutation was 340C>T and amino acid change was Arg114Cys. The sequence of KRT13
      was highly conserved. Real-Time RT-PCR and Western blot analysis results show
      that KRT13 expression level is lower in patient but keep almost no change in mRNA
      level. When cells were treated with MG132, KRT13 protein level was increased and
      kept almost the same in normal and patient cells. We identified two heritable
      mutations in the KRT13 gene, which were associated with the development of WSN.
      The abnormal degradation of KRT13 protein of WSN may probably associate with the
      abnormal ubiquitination process. 

PMID- 25606423
TI  - Four pairs of gene-gene interactions associated with increased risk for type 2
      diabetes (CDKN2BAS-KCNJ11), obesity (SLC2A9-IGF2BP2, FTO-APOA5), and hypertension
      (MC4R-IGF2BP2) in Chinese women.
AB  - Metabolic disorders including type 2 diabetes, obesity and hypertension have
      growing prevalence globally every year. Genome-wide association studies have
      successfully identified many genetic markers associated to these diseases, but
      few studied their interaction effects. In this study, twenty candidate SNPs from
      sixteen genes are selected, and a lasso-multiple regression approach is
      implemented to consider the SNP-SNP interactions among them in an Asian
      population. It is found out that the main effects of the markers are weak but the
      interactions among the candidates showed a significant association to diseases.
      SNPs from genes CDKN2BAS and KCNJ11 are significantly associated to risk for
      developing diabetes, and SNPs from FTO and APOA5 might interact to play an
      important role for the onset of hypertension. 

PMID- 25606424
TI  - Association of the endothelial nitric oxide synthase gene G894T polymorphism with
      the risk of diabetic nephropathy in Qassim region, Saudi Arabia-A pilot study.
AB  - BACKGROUND: Diabetic nephropathy (DN) is a chronic microangiopathic complication
      of type 2 diabetes mellitus (DM).Vascular endothelial dysfunction resulting from
      impaired nitric oxide synthase (NOS) activity in the vascular endothelial cells
      has been suggested as playing an important role in the pathogenesis of diabetic
      nephropathy (DN). Endothelial nitric oxide synthase (E-NOS) gene G894T
      polymorphism has been reported to be associated with endothelial dysfunction
      leading to DN. Our objective was to evaluate the association of G894T
      polymorphism of eNOS gene with the risk of DN among type 2 diabetic Saudi
      patients. METHODS: One hundred and twenty subjects were included in this study.
      They were divided into three groups. Group I, 40 controls. Group II, 40 type 2
      diabetic patients without nephropathy. Group III, 40 type2 diabetic patients with
      nephropathy. Endothelial nitric oxide synthase (eNOS) G894Tpolymorphism was
      detected by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). Plasma nitric oxide (NO) levels were estimated. RESULTS: E-NOS
      genotype frequency showed non-significant differences among the all studied
      groups (p > 0.05). Both diabetic groups had significantly higher plasma nitrate
      levels than in controls with a significant increase in group III than in group II
      patients (all p < 0.0001). E NOS 894TT genotype was associated with higher plasma
      nitrate levels in all groups. CONCLUSION: E-NOS gene SNP is not considered as
      genetic risk factor for DN among type 2 diabetic Saudi patients. The higher
      plasma levels of nitrates as a marker of oxidative stress in diabetic patients
      with nephropathy suggest the possible role of oxidative stress but not e-NOS gene
      SNP in pathogenesis of the DN.

PMID- 25606425
TI  - Pitfalls in the prenatal diagnosis of mucolipidosis II alpha/beta: A case report.
AB  - Mucolipidosis II alpha/beta is an autosomal recessive disorder caused by
      deficient activity of GlcNAc-1-phosphotransferase. We report the prenatal
      diagnosis of a fetus who was found to exhibit normal levels of lysosomal enzymes
      in the amniotic fluid but low levels in amniocytes, and who was found to be
      heterozygous for the most common GNPTAB mutation. As in some carriers of
      Mucolipidosis II biochemical abnormalities may hinder prenatal diagnosis, we
      suggest DNA analysis should be performed whenever possible. 

PMID- 25606426
TI  - Genome-wide identification and expression pattern of drought-responsive members
      of the NAC family in maize.
AB  - NAC proteins are plant-specific transcription factors (TFs). Although they play a
      pivotal role in regulating distinct biological processes, TFs in maize are yet to
      be investigated comprehensively. Within the maize genome, we identified 152
      putative NAC domain-encoding genes (ZmNACs), including eight membrane-bound
      members, by systematic sequence analysis and physically mapped them onto ten
      chromosomes of maize. In silico analysis of the ZmNACs and comparison with
      similar genes in other plants such as Arabidopsis, rice, and soybean, revealed a
      similar NAC sequence architecture. Phylogenetically, the ZmNACs were arranged
      into six distinct subgroups (I-VI) possessing conserved motifs. Phylogenetic
      analysis using stress-related NAC TFs from Arabidopsis, rice, and soybean as
      seeding sequences identified 24 of the 152 ZmNACs (all from Group II) as putative
      stress-responsive genes, including one dehydration-responsive ZmSNAC1 gene
      reported earlier. One drought-tolerant genotype (HKI577) and one susceptible
      genotype (PC13T-3) were used for studying the expression pattern of the NAC genes
      during drought stress. qRT-PCR based expression profiles of 11 genes predicted to
      be related to stress confirmed strong differential gene expression during drought
      stress. Phylogenetic analyses revealed that ZmNAC18, ZmNAC51, ZmNAC145, and
      ZmNAC72, which were up-regulated in the tolerant genotype and down-regulated in
      the susceptible genotype, belonged to the same group to which also belong other
      drought-responsive genes, namely SNAC1, OsNAC6, ANAC019, and ANAC055, which act
      as a transcriptional activator and are strongly induced under stress from various
      abiotic sources. Differentially expressed ZmNAC genes, alone or in combination
      with each other or with other type(s) of TFs, may control the general cellular
      machinery and regulate stress-responsive downstream genes. Alternatively, they
      may serve as a platform to regulate a broad set of genes, which are subsequently
      fine-tuned by specific regulators. This genome-wide identification and expression
      profiling opens new avenues for systematic functional analysis of new members of
      the NAC gene family, which may be exploited in developing lines that are better
      adapted to drought. 

PMID- 25606427
TI  - Genetic ancestry of a Moroccan population as inferred from autosomal STRs.
AB  - Detecting population substructure and ancestry is a critical issue for both
      association studies of health behaviors and forensic genetics. Determining
      aspects of a population's genetic history as potential sources of substructure
      can aid in design of future genetic studies. Within this context, fifteen
      autosomal short tandem repeat (STR), were used to examine population genetic
      structure and hypotheses of the origin of the modern Moroccan population from
      individuals belonging to three different ethnical groups from Morocco (Arab,
      Berber and Sahrawi), by comparing their autosomal STR variation with that of
      neighboring and non-neighboring populations in North Africa, Europe and Middle
      East as well as proposed ancestral populations in Morocco (Berber). We report on
      the results that the gradient of North African ancestry accounts for previous
      observations of low levels of sharing with Near East and a substantially
      increased gene flow especially from Morocco and Spain. 

PMID- 25606428
TI  - Designing, optimization and validation of tetra-primer ARMS PCR protocol for
      genotyping mutations in caprine Fec genes.
AB  - New, quick, and inexpensive methods for genotyping novel caprine Fec gene
      polymorphisms through tetra-primer ARMS PCR were developed in the present
      investigation. Single nucleotide polymorphism (SNP) genotyping needs to be
      attempted to establish association between the identified mutations and traits of
      economic importance. In the current study, we have successfully genotyped three
      new SNPs identified in caprine fecundity genes viz. T(-242)C (BMPR1B), G1189A
      (GDF9) and G735A (BMP15). Tetra-primer ARMS PCR protocol was optimized and
      validated for these SNPs with short turn-around time and costs. The optimized
      techniques were tested on 158 random samples of Black Bengal goat breed. Samples
      with known genotypes for the described genes, previously tested in duplicate
      using the sequencing methods, were employed for validation of the assay. Upon
      validation, complete concordance was observed between the tetra-primer ARMS PCR
      assays and the sequencing results. These results highlight the ability of tetra
      primer ARMS PCR in genotyping of mutations in Fec genes. Any associated SNP could
      be used to accelerate the improvement of goat reproductive traits by identifying
      high prolific animals at an early stage of life. Our results provide direct
      evidence that tetra-primer ARMS-PCR is a rapid, reliable, and cost-effective
      method for SNP genotyping of mutations in caprine Fec genes. 

PMID- 25606429
TI  - Sequence analysis and identification of new variations in the coding sequence of
      melatonin receptor gene (MTNR1A) of Indian Chokla sheep breed.
AB  - Melatonin receptor 1A gene is the prime receptor mediating the effect of
      melatonin at the neuroendocrine level for control of seasonal reproduction in
      sheep. The aims of this study were to examine the polymorphism pattern of coding
      sequence of MTNR1A gene in Chokla sheep, a breed of Indian arid tract and to
      identify new variations in relation to its aseasonal status. Genomic DNAs of 101
      Chokla sheep were collected and an 824 bp coding sequence of Exon II was
      amplified. RFLP was performed with enzyme RsaI and MnlI to assess the presence of
      polymorphism at position C606T and G612A, respectively. Genotyping revealed
      significantly higher frequency of M and R alleles than m and r alleles. RR and MM
      were found to be dominantly present in the group of studied population. Cloning
      and sequencing of Exon II followed by mutation/polymorphism analysis revealed ten
      mutations of which three were non-synonymous mutations (G706A, C893A, G931C).
      G706A leads to substitution of valine by isoleucine Val125I (U14109) in the fifth
      transmembrane domain. C893A leads to substitution of alanine by aspartic acid in
      the third extracellular loop. G931C mutation brings about substitution of amino
      acid alanine by proline in the seventh transmembrane helix, can affect the
      conformational stability of the molecule. Polyphen-2 analysis revealed that the
      polymorphism at position 931 is potentially damaging while the mutations at
      positions 706 and 893 were benign. It is concluded that G931C mutation of MTNR 1A
      gene, may explain, in part, the importance of melatonin structure integrity in
      influencing seasonality in sheep. 

PMID- 25606430
TI  - Genetic diversity and relationship of Hedychium from Northeast India as dissected
      using PCA analysis and hierarchical clustering.
AB  - Molecular genetic fingerprints of eleven Hedychium species from Northeast India
      were developed using PCR based markers. Fifteen inter-simple sequence repeats
      (ISSRs) and five amplified fragment length polymorphism (AFLP) primers produced
      547 polymorphic fragments. Positive correlation (r = 0.46) was observed between
      the mean genetic similarity and genetic diversity parameters at the inter-species
      level. AFLP and ISSR markers were able to group the species according to its
      altitude and intensity of flower aroma. Cophenetic correlation coefficients
      between the dendrogram and the original similarity matrix were significant for
      ISSR (r = 0.89) compared to AFLP (r = 0.83) markers. This genetic
      characterization of Hedychium from Northeast India contributes to the knowledge
      of genetic structure of the species and can be used to define strategies for
      their conservation and management. 

PMID- 25606431
TI  - A novel CHD7 mutation in a Chinese patient with CHARGE syndrome.
AB  - In Genetics Out-patient Department of Shanghai Children's Medical Center, we
      consulted a 3-year-old boy with multiple anomaly syndrome (congenital heart
      disease, cryptorchidism, congenital deafness, mental retardation, exophthalmos,
      laryngeal cartilage dysplasia and high arched palate). We ruled out the
      possibility of multiple deformities caused by genomic imbalances. The patient was
      then clinically considered to have CHARGE syndrome, an autosomal dominant multi
      system disorder involving defects in multiple organs, and CHD7 is the only known
      gene associated with the syndrome. Sequencing analysis of CHD7 of the proband
      identified a de novo heterogeneous mutation (c.2916_2917del, p.Gln972HisfsX22), a
      two-nucleotide deletion causing reading frame shift and resulting in a truncated
      CHD7 protein. Computational structure analysis suggests that the truncated
      protein only contains the chromodomains of CHD7, but lacks the SWI2/SNF2-like
      ATPase/helicase domain and the DNA binding domain, which are indispensable for
      the proper function of the protein, especially on chromatin remodeling. The
      patient then received follow up treatment in different clinical departments in a
      long period. To our best knowledge, this is the first CHARGE syndrome in Chinese
      patients diagnosed by gene analysis. In summary, the clinical symptoms and the
      description of treatment in the present case, combined with genetic test and
      functional prediction of CHD7, are helpful for further understanding and genetic
      counseling of the CHARGE syndrome. 

PMID- 25606432
TI  - Cloning and characterization of a ribosomal protein L23a gene from Small Tail Han
      sheep by screening of a cDNA expression library.
AB  - As an indispensable component of the eukaryotic ribosome, ribosomal protein L23a
      plays an important role in protein synthesis, folding and sorting. In this study,
      the cDNA fragment of ribosomal protein L23a with 471 bp in size was screened from
      the Small Tail Han sheep ear marginal tissue cDNA expression library, it has 157
      amino acids and a molecular weight of 17.69 kDa. The nucleotide sequence of L23a
      shares a high homology with those of human, mouse, cattle and pig of 91.51%,
      88.32%, 96.18% and 93.84%, respectively. L23a is highly basic, containing a
      combined 45 Arg, Lys, and His residues and only 14 Asp and Glu residues. The
      expression pattern and intra-cellular distribution of recombinant L23a proteins
      in Ujumqin sheep fibroblast cells were analyzed after transfected with the
      plasmid pEGFP-N3-RPL23A, there were green fluorescence signals both in the
      cytoplasm and nucleolus of transfected cells after 24 h, the number of positive
      cells was increased with time, and they reached the peak level after 48 h of
      transfection. The transfection efficiency was 22.8%. Expression patterns of
      recombinant L23a gene in Escherichia coli were different with induction
      temperature, inductor concentration and induction time, when the IPTG
      concentration was 0.1 mmol/L and induction temperature was 37 degrees , L23a
      protein expression was increased with induction time. 

PMID- 25606433
TI  - Genetic stability and phytochemical analysis of the in vitro regenerated plants
      of Dendrobium nobile Lindl., an endangered medicinal orchid.
AB  - An efficient genetically stable regeneration protocol with increased
      phytochemical production has been established for Dendrobium nobile, a highly
      prized orchid for its economic and medicinal importance. Protocorm like bodies
      (PLBs) were induced from the pseudostem segments using thidiazuron (TDZ; 1.5
      mg/l), by-passing the conventional auxin-cytokinin complement approach for plant
      regeneration. Although, PLB induction was observed at higher concentrations of
      TDZ, plantlet regeneration from those PLBs was affected adversely. The best
      rooting (5.41 roots/shoot) was achieved in MS medium with 1.5 mg/l TDZ and 0.25%
      activated charcoal. Plantlets were successfully transferred to a greenhouse with
      a survival rate of 84.3%, exhibiting normal development. Genetic stability of the
      regenerated plants was investigated using randomly amplified polymorphic DNA
      (RAPD) and start codon targeted (SCoT) polymorphism markers which detected 97% of
      genetic fidelity among the regenerants. The PIC values of RAPD and SCoT primers
      were recorded to be 0.92 and 0.76 and their Rp values ranged between 3.66 and 10,
      and 4 and 12 respectively. The amplification products of the regenerated plants
      showed similar banding patterns to that of the mother plant thus demonstrating
      the homogeneity of the micropropagated plants. A comparative phytochemical
      analysis among the mother and the micropropagated plants showed a higher yield of
      secondary metabolites. The regeneration protocol developed in this study provides
      a basis for ex-situ germplasm conservation and also harnesses the various
      secondary metabolite compounds of medicinal importance present in D. nobile. 

PMID- 25606434
TI  - Polymorphisms in thrombophilic genes are associated with deep venous
      thromboembolism in an Iranian population.
AB  - It has been revealed that the inherited thrombophilia increases the risk of
      thrombosis in the venous system. To study the association of factor V G1691A,
      factor V HR2 (4070A/G), prothrombin G20210A, and PAI-1 (- 675 I/D, 5G/4G)
      polymorphisms with deep venous thromboembolism (DVT), these polymorphisms were
      investigated. A total of 193 patients who presented clinical symptoms of deep
      venous thromboembolism including 103 men and 90 women, and 500 healthy
      individuals without both personal and family histories of thromboembolic
      disorders including 275 men and 225 women were recruited into the study.
      Genotyping was carried out using the amplification refractory mutation system
      polymerase chain reaction (ARMS-PCR) technique. Our results showed that the
      genotype distribution for FV (G1691A and A4070G) and PAI-1 4G/5G polymorphisms in
      DVT patients were significantly higher than healthy control (P < 0.05). Also, the
      mutant allele frequencies for all studied polymorphisms differed significantly
      between the case and control groups (P < 0.05). We concluded that the prevalence
      of FV (G1691A and A4070G) and PAI-1 4G/5G polymorphisms increased the risk of DVT
      occurrence in subjects. These findings provide additional evidence to support the
      hypothesis that thrombophilic gene polymorphisms are involved in vascular
      thromboembolism. 

PMID- 25606435
TI  - Association of the histone-lysine N-methyltransferase MLL5 gene with coronary
      artery disease in Chinese Han people.
AB  - BACKGROUND: MLL5, a member of the histone-lysine N-methyltransferase family, has
      been implicated in the control of the cell cycle progression and survival. The
      aim of this study was to explore the relationship between the interaction of
      histone-lysine N-methyltransferase MLL5 gene polymorphism and CAD in a Chinese
      Han population. METHODS: Using a case-control study of Chinese CAD patients (n =
      565) and healthy controls (n = 694), we investigated the MLL5 gene polymorphism
      by the use of polymerase chain reaction fragment length polymorphism (PCR-RFLP)
      analysis. RESULTS: For total, the distribution of SNP1 (rs12671368) and SNP2
      (rs2192932) genotypes showed a significant difference between CAD and control
      participants (P1 = 0.03, P2 = 0.02). For total the distribution of SNP1
      (rs12671368) and SNP2 (rs2192932) alleles in the dominant model (GG vs. AA + AG)
      and the recessive model (AA vs. AG + GG) showed a significant difference between
      CAD and control participants (for allele: P1 < 0.01 and P2 = 0.05, for dominant
      model: P1 > 0.05 and P2 = 0.02, for recessive model: P1 = 0.03 and P2 = 0.78,
      respectively). For total the significant difference of the distribution of SNP1
      and SNP2 in the dominant model and recessive model was retained after adjusting
      for covariates (for dominant model: SNP1 OR: 1.68, 95% confidence interval [CI]:
      1.08-2.64, P = 0.02; SNP2 OR: 0.51, 95% CI: 0.36-0.72, P = 0.01; for recessive
      model: SNP1 OR: 1.84, 95% confidence interval [CI]: 1.28-2.64, P < 0.01; SNP2 OR:
      0.65, 95% CI: 0.35-1.22, P = 0.18). CONCLUSIONS: The GG genotype of rs12671368
      and the AA genotype of rs2192932 in the MLL5 gene could be protective genetic
      markers of CAD.

PMID- 25606436
TI  - Potential antioxidant response to coffee - A matter of genotype?
AB  - In a human intervention study, coffee combining natural green coffee bean
      constituents and dark roast products was identified as a genotype-dependent
      inducer of the Nrf2/ARE pathway, significantly affecting Nrf2 gene expression and
      downstream GST1A1 and UGT1A1 gene transcription. The observed transcriptional
      changes correlated with the presence of specific Nrf2 genotypes suggesting their
      influence on both Nrf2 and subsequent ARE-dependent GST1A1 and UGT1A1
      transcription. While the presence of the - 653 SNP seems to be advantageous,
      resulting in higher Nrf2, GST1A1 and UGT1A1 gene transcription following coffee
      consumption, in contrast, the presence of the - 651 SNP significantly down
      regulated the response to the study coffee. Furthermore, the presence of the B/B
      genotype in GST1A1 along with the frequency of the [TA]6/6 and [TA]7/7
      polymorphisms in UGT1A1 appeared to significantly increase sensitivity toward
      coffee-induced gene transcription. This data suggests that when examining the
      role of the Nrf2/ARE pathway in the regulation of antioxidative and
      chemopreventive phase II efficacy, individual genotypes should be included when
      considering the potency of bioactive food/food constituents and their therapeutic
      potential. 

PMID- 25606438
TI  - SLC34A2 gene compound heterozygous mutation identification in a patient with
      pulmonary alveolar microlithiasis and computational 3D protein structure
      prediction.
AB  - We recently diagnosed a patient with pulmonary alveolar microlithiasis (PAM).
      Because loss-of-function mutations of the SLC34A2 gene are responsible for the
      development of PAM, we sought to sequence the SLC34A2 gene of the patient and his
      direct relatives, with a purpose to identify mutations that caused the PAM of the
      patient as well as the carriers of his family. We found a novel compound
      heterozygous mutation of the SLC34A2 gene in this patient, which were the
      mutations of c.1363T > C (p. Y455H) in exon 12 and c.910A > T (p. K304X) in exon
      8. Computational prediction of three-dimensional (3D) structures of the mutants
      revealed that the Y455H mutation resulted in a formation of irregular coils in
      the trans-membrane domain and the K304X mutation resulted in protein truncation.
      Our study suggested that sequencing of the SLC34A2 gene together with a
      computational prediction of the 3D structures of the mutated proteins may be
      useful in PAM diagnosis and prognosis. 

PMID- 25606437
TI  - Association of vitamin D and vitamin D receptor gene polymorphisms with chronic
      inflammation, insulin resistance and metabolic syndrome components in type 2
      diabetic Egyptian patients.
AB  - BACKGROUND: To date the published data concerning the possible interplay between
      vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the
      immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient.
      Some of the immune non-classical actions of vitamin D may point to its role in
      the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6).
      Although there is evidence to support a relationship among vitamin D status,
      chronic inflammation and insulin resistance, the underlying mechanism requires
      further exploration. We aimed to investigate the role of vitamin D in chronic
      inflammation and insulin resistance in type 2 DM. Moreover, to examine the
      association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A >
      G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic
      Egyptian patients . SUBJECTS AND METHODS: A total of 190 subjects were enrolled
      in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II
      was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients
      with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done
      in all subjects. VitD and IL-6 plasma levels were estimated. RESULTS: The TT
      genotype for the VDR FokI was significantly more frequent in subgroup IIb than in
      subgroup IIa and controls (X (2) = 6.83, P = 0.03 and X (2) = 16.592, P = 0.000)
      respectively. The T allele was more frequent in the MetSyn group as compared to
      diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele
      of C > T (FokI) = 2.30 (1.37-3.86). We did not detect any significant difference
      in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR
      was significantly associated with the lipid profile parameters, VitD and IL-6
      plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6
      levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while
      BsmI VDR variant was associated only with VitD values in both subgroups.
      CONCLUSION: The present study suggests an interaction between VDR polymorphisms
      and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6).
      FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance
      and might represent a genetic determinant for developing MetSyn in type 2
      diabetic Egyptian patients. The challenge is determining the mechanisms of VitD
      action for recommendation of VitD supplementation that reduces the risks of
      MetSyn, insulin resistance and progression to type 2 diabetes.

PMID- 25606439
TI  - Association between CETP, MLXIPL, and TOMM40 polymorphisms and serum lipid levels
      in a Latvian population.
AB  - BACKGROUND: Abnormal lipid levels are considered one of the most significant risk
      factors for atherosclerosis and coronary artery disease, two of the main causes
      of death worldwide. Apart from monogenic cases of hypercholesterolemia, most of
      the common dyslipidemias are caused by a number of low-impact polymorphisms. It
      has recently been reported that frequent polymorphisms at a large number of loci
      are significantly associated with one or more blood lipid parameters in many
      populations. Identifying these associations in different populations and
      estimating the possible interactions between genetic models are necessary to
      explain the underlying genetic architecture of the associated loci and their
      ultimate impact on lipid-associated traits. METHODS: We estimated the association
      between 144 common single-nucleotide polymorphisms (SNPs) from published genome
      wide association studies and the levels of total cholesterol, low- and high
      density lipoprotein-cholesterol, and triglycerides in 1273 individuals from the
      Genome Database of the Latvian Population. We analyzed a panel of 144 common SNPs
      with Illumina GoldenGate Genotyping Assays on the Illumina BeadXpress System.
      RESULTS: Ten SNPs at the CETP locus and two at the MLXIPL locus were associated
      with reduced high-density lipoprotein-cholesterol levels; one SNP at the TOMM40
      locus was associated with increased low-density lipoprotein-cholesterol; and four
      SNPs at the MLXIPL locus were associated with increased log triglyceride levels.
      There was also a significant correlation between the number of risk alleles and
      all the lipid parameters, suggesting that the coexistence of many low-impact SNPs
      has a greater effect on the dyslipidemia phenotype than the individual effects of
      found SNPs. CONCLUSION: We conclude that the CETP, MLXIPL, and TOMM40 loci are
      the strongest genetic factors underlying the variability in lipid traits in our
      population.

PMID- 25606440
TI  - IRS1 gene polymorphisms Gly972Arg and Ala513Pro are not associated with insulin
      resistance and type 2 diabetes risk in non-obese Turkish population.
AB  - Insulin receptor substrate 1 (IRS1), plays a critical role in insulin signaling
      and its control has an important place in the development of insulin resistance.
      The tyrosine phosphorylation of IRS1 serves as docking molecules for downstream
      effectors such as Phosphatidylinositol 3-kinase and phosphotyrosine phosphatase
      2. We focused on the Gly972Arg and Ala513Pro variants of the IRS1 gene, since
      these specific allelic variants are located near the Tyr-Met-X-Met (YMXM) motifs
      around Tyr987 and Tyr612. Thus, we aimed to investigate the effects of
      Gly972Arg/Ala513Pro polymorphisms in IRS1 gene on development of insulin
      resistance and the risk of type 2 diabetes in a non-obese Turkish population.
      This work included 306 individuals comprising 178 subjects with type 2 diabetes
      and 128 healthy subjects matched for body mass index. Gly972Arg/Ala513Pro
      polymorphisms had no effect on type 2 diabetes risk and its phenotypes (P >
      0.05). Although IRS1 gene and its variants are associated with type 2 diabetes
      and insulin resistance in several studies worldwide, our data showed that there
      is no association between Gly972Arg and Ala513Pro variants in IRS1 and disease in
      Turkish population. 

PMID- 25606441
TI  - In silico analysis of single nucleotide polymorphism (SNP) in human TNF-alpha
      gene.
AB  - The TNF-alpha gene mutations are seen in many diseases especially inflammatory
      diseases. Hence, before planning a larger population study, it is advisable to
      sort out the possible functional SNPs. To accomplish this goal, data available in
      the dbSNP database and different computer programs can be used. Therefore, this
      study was undertaken to find the functional nsSNPs (non-synonymous single
      nucleotide polymorphisms) in TNF-alpha. Out of the total 169 SNPs, 48 were nsSNPs
      (non-synonymous single nucleotide polymorphisms), 23 occurred in the mRNA 3' UTR,
      10 occurred in 5' UTR region, 41 occurred in intronic regions and the rest were
      other types of SNPs. SIFT and PolyPhen predicted 2 out of 48 nsSNPs as damaging.
      Among the predicted nsSNPs, rs4645843 and rs1800620 were identified as
      deleterious and damaging by the SIFT (Sorting Intolerant from Tolerant) and
      PolyPhen programs. Additionally, I-Mutant and nsSNPAnalyzer showed a decrease in
      stability for these nsSNPs upon mutation. Protein structural analysis with these
      amino acid variants was performed by using I-Mutant, Swiss PDB viewer, ANOLEA
      (Atomic Non-Local Environment Assessment), MUSTER (MUlti-Sources ThreadER) and
      NOMAD-Ref servers to check their molecular dynamics and energy minimization
      calculations. This study suggested that P84L and A94T variants of TNF-alpha could
      directly or indirectly destabilize the amino acid interactions and hydrogen bond
      networks thus explaining the functional deviations of protein to some extent. 

PMID- 25606442
TI  - Epidemiology of prostate cancer in India.
AB  - Data from national cancer registries shows that incidence of certain cancers are
      on rise in India. The cancers which are showing significant increase in incidence
      rates include prostate, mouth and kidney among male population, corpus uteri,
      breast and thyroid among female population and lung cancer in both male and
      female populations. In the present review article we have focused on epidemiology
      of prostate cancer in Indian subcontinent in terms of incidence, survival, and
      mortality etc. The article presents the incidence rates, mortality and trends
      over time for prostate cancer as the data collected from national population
      based cancer registries. Prostate is the second leading site of cancer among
      males in large Indian cities like Delhi, Kolkatta, Pune and Thiruvananthapuram,
      third leading site of cancer in cities like Bangalore and Mumbai and it is among
      the top ten leading sites of cancers in the rest of the population based cancer
      registries (PBCRs) of India. The PBCRs at Bangalore (Annual Percentage Change:
      3.4%), Chennai (4.2%), Delhi (3.3%), Mumbai (0.9%) and Kamrup Urban District
      (11.6%) recorded a statistically significant increasing trend in incidence rates
      over time. 

PMID- 25606443
TI  - Genome wide analysis of Arabidopsis thaliana reveals high frequency of AAAGN7CTTT
      motif.
AB  - Sequence specific elements in DNA regulate transcription by recruiting
      transcription factors. The Dof proteins are a large family of transcription
      factors that share a single highly conserved zinc finger. The core to which Dof
      proteins bind has a consensus AAAG or ACTTTA sequence. These motifs have been
      over represented in many promoters. We performed a genome wide analysis of AAAG
      repeat elements increasing the spacer length from 0 to 25. Similar analyses was
      done with AAAG-CTTT motifs. We report unusual high frequency of AAAGN7CTTT in
      Arabidopsis thaliana genome. We also conclude that there is a preference for A/G
      nucleotides in spacer sequence between two AAAG repeats. 

PMID- 25606444
TI  - Pollitt syndrome patients carry mutation in TTDN1.
AB  - Complete human genome sequencing was used to identify the causative mutation in a
      family with Pollitt syndrome (MIM #275550), comprising two non-consanguineous
      parents and their two affected children. The patient's symptoms were reminiscent
      of the non-photosensitive form of recessively inherited trichothiodystrophy
      (TTD). A mutation in the TTDN1/C7orf11 gene, a gene that is known to be involved
      in non-photosensitive TTD, had been excluded by others by Sanger sequencing.
      Unexpectedly, we did find a homozygous single-base pair deletion in the coding
      region of this gene, a mutation that is known to cause non-photosensitive TTD.
      The deleterious variant causing a frame shift at amino acid 93 (C326delA)
      followed the right mode of inheritance in the family and was independently
      validated using conventional DNA sequencing. We expect this novel DNA sequencing
      technology to help redefine phenotypic and genomic variation in patients with
      (mono) genetic disorders in an unprecedented manner. 

PMID- 25606446
TI  - Role of transforming growth factor-beta1 in serum and - 509 C>T promoter gene
      polymorphism in development of liver cirrhosis in Egyptian patients.
AB  - OBJECTIVES: Liver cirrhosis is a condition in which the liver slowly deteriorates
      and malfunctions due to chronic injury. HCV is one of the major causes of liver
      fibrosis and ultimate progression to cirrhosis. Transforming growth factor-beta1
      (TGF-beta1), one of the three isoforms of TGF-beta, is a pleiotrophic cytokine
      that regulates the proliferation and differentiation of cells, embryonic
      development, wound healing and angiogenesis. This study aimed to evaluate the
      role of serum TGF-beta1 and - 509 C>T promoter gene polymorphism in the
      development of liver cirrhosis. DESIGN AND METHODS: Besides routine liver
      profiles, serum TGF-beta1 was measured in 40 liver cirrhosis patients and 40
      controls using ELISA technique. TGF-beta1 - 509 C>T promoter gene polymorphism
      was detected using PCR-RFLP technique. RESULTS: TGF-beta1 - 509 CT and TT
      genotype frequencies were significantly higher in the cirrhotic group (52.5%,
      25%; respectively) than control group (10%, 7.5%; respectively); OR = 16.238 (95%
      CI 5.391-48.914, p < 0.05). The - 509 T allele carriers are more prone to develop
      liver cirrhosis than - 509 C allele carriers; OR = 7.359 (95% CI 3.325-16.288, p
      < 0.05). Serum TGF-beta1 was significantly higher in cirrhotic group (11.79 +/-
      1.45 ng/ml) than control group (8.67 +/- 1.23 ng/ml); p < 0.05. Also serum TGF
      beta1 was significantly higher in TT genotype than CT and CC genotypes (p <
      0.05). A significant positive correlation was observed between serum TGF-beta1
      and alkaline phosphatase (r = 0.559, p < 0.05); AST (r = 0.573, p < 0.05). A
      significant negative correlation was observed between serum TGF-beta1 and albumin
      (r = - 0.331, p < 0.05). CONCLUSION: There is an association between serum TGF
      beta1, - 509 CT and TT genotypes of TGF-beta1 gene and the higher risk for liver
      cirrhosis development of liver cirrhosis.

PMID- 25606445
TI  - BTNL2 gene SNPs as a contributing factor to sarcoidosis pathogenesis in a cohort
      of Greek patients.
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown etiology that
      primarily affects adults between the ages of 20 and 40 years old. It is
      characterized by the activation of Th1 lymphocytes resulting in the production of
      inflammatory cytokines and the formation of noncaseating epithelioid cell
      granulomas in affected tissues. The lungs and lymphatic system are the ones most
      frequently affected. The disease usually presents spontaneous remission in the
      first two years and, in a few patients, the disease progresses to pulmonary
      fibrosis or other fatal complications depending on the affected organ. The
      pathogenesis of sarcoidosis is still not clearly defined, and is considered an
      interaction between the environment and risk alleles in many genes. The present
      case control study consisted of 146 Greek patients with sarcoidosis and 90
      healthy volunteers from the same ethnic group. The coding and neighboring
      intronic regions of the BTNL2 gene were sequenced and risk alleles were compared
      amongst the two groups. Thirty-seven different variants were detected from which
      12 were synonymous substitutions and 25 non-synonymous. With the help of in
      silico tools (SIFT, PolyPhen, PROVEAN, PMut and EX_SKIP), 13 variants were
      classified as possible pathological risk variants including 4 novel ones. The
      most common risk variants contributing to phenotypic modulation of sarcoidosis
      were p.S360G and p.S334L, with the latter contributing to a more severe disease
      stage with extra-pulmonary manifestations such as skin granulomas and relapses
      being more common. 

PMID- 25606447
TI  - Familial hypercholesterolemia: Molecular characterization of possible cases from
      the Azores Islands (Portugal).
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder of the
      cholesterol metabolism, which constitutes a risk factor for coronary arterial
      disease (CAD). In the Azores Islands (Portugal), where mortality from CAD doubles
      its rate comparatively to the rest of the country and where a high frequency of
      dyslipidemia has been reported, the prevalence and distribution of FH remain
      unknown. The molecular characterization of a group of 33 possible cases of FH of
      Azorean background was undertaken in this study. A DNA array was initially used
      to search mutations in the LDLR, APOB and PCSK9 loci in 10 unrelated possible
      cases of FH. No mutations were detected in the array; after sequencing the full
      LDLR gene, 18 variants were identified, corresponding to two missense (c.806G >
      A; c.1171G > A) and sixteen synonymous alterations. Six of the synonymous
      variants which are consistently described in the literature as associated with
      altered cholesterol levels were used to build haplotypes. The most frequent
      haplotype corresponded to TTCGCC (45%), a "risk" haplotype, formed exclusively by
      alleles that were reported to increase cholesterol levels. Some of the variants
      detected in the full sequencing of the LDLR gene fell within the ligand-binding
      domain of this gene, defined by exons 2 to 6. To add information as to the role
      of such variants, these exons were sequenced in the remaining 23 possible FH
      cases. Two missense alterations (c.185C > T; c.806G > A) were found in this
      subset of possible FH cases. The missense alteration c.185C > T, identified in
      one individual, is novel for the Portuguese population. In silico analysis was
      not conclusive for this alteration, whose role will have to be further
      investigated. This study represents the first approach to the establishment of
      the mutational profile of FH in the Azores Islands. 

PMID- 25606448
TI  - Vitamin-D receptor (VDR) gene polymorphisms (Taq-I & Apa-I) in Syrian healthy
      population.
AB  - The vitamin D endocrine system regulates bone metabolism and calcium homeostasis
      as well as cellular proliferation and differentiation. Vitamin D receptor (VDR)
      mediates Vit-D activity, thus VDR gene polymorphisms may correlate with different
      diseases. This study aimed to determine the distribution of VDR gene (Taq-I and
      Apa-I) polymorphisms using a RFLP in unrelated normal healthy individuals of
      Syrian population. Allelic frequencies were 65% vs 35% and 66% vs 34% for T vs t
      and A vs a alleles, respectively. Genotype distribution was 36%, 58% and 6% for
      TT, Tt and tt and 42%, 47% and 10% for AA, Aa and aa, respectively. These results
      demonstrate that the frequency and distribution of the VDR polymorphisms in
      Syrian population are different from other populations worldwide. 

PMID- 25606449
TI  - Association of Versican (VCAN) gene polymorphisms rs251124 and rs2287926 (G428D),
      with intracranial aneurysm.
AB  - Intracranial aneurysm (IA) accounts for 85% of Subarachnoid Hemorrhage (SAH) and
      is mainly caused due to the weakening of arterial wall. The structural integrity
      of the intracranial arteries is mainly influenced by the extracellular matrix
      (ECM) remodeling. The Proteoglycan Versican plays an important role in
      extracellular matrix assembly and plays a major role in the pathogenesis of IA.
      The linkage studies also indicated VCAN as a putative candidate gene for IA in
      the 5q22-31 region. Using a case-control study design, we tested the hypothesis
      whether the variants in VCAN gene, nonsynonymous variants in the coding region of
      Glycosaminoglycan alpha (GAG-alpha) and GAG-beta and two reported SNPs involved
      in splicing rs251124 and rs173686 can increase the risk of aSAH among South
      Indian patients, either independently, or by interacting with other risk factors
      of the disease. We selected 200 radiologically confirmed aneurysmal cases and 250
      ethnically, age and sex matched controls from the Dravidian Malayalam speaking
      population of South India. The present study reiterated the earlier association
      of rs251124 with intracranial aneurysm (P = 0.0002) and also found a novel
      association with rs2287926 (G428D) in exon 7 coding for GAG-alpha with
      intracranial aneurysm (P = 0.0015). Interestingly, both these SNPs contributed to
      higher risk for aneurysm in males. In-silico analysis predicted this SNP to have
      the highest functional relevance in the gene which might have a potentially
      altered regulatory role in transcription and splicing. Using meta-analysis with
      available literature rs251124 was found to be the strongest intracranial aneurysm
      marker for global ethnicities. This study with a novel functional SNP rs2287926
      (G428D) further substantiates the potential role of VCAN in the pathogenesis of
      IA. 

PMID- 25606450
TI  - ACE-II genotype and I allele predicts ischemic stroke among males in south India.
AB  - Two hundred ischemic stroke patients and 193 age and sex matched healthy controls
      were studied for the presence of Angiotensin Converting Enzyme Insertion/Deletion
      (ACE I/D) gene polymorphism. The PCR studies revealed that ACE 'II' (OR = 2.055;
      p = 0.004) genotype and 'I' (OR = 1.411; p = 0.018) alleles were significantly
      associated with IS patients. Gender specific analysis revealed a strong
      association of 'II' (OR = 2.044; p = 0.014) genotype and 'I' (OR = 1.531; p =
      0.011) allele with male sex. Classification of patients based on TOAST criteria,
      revealed a significant association for 'II' genotype (OR = 1.713; p = 0.043) and
      'I' (OR = 1.382; p = 0.039) allele in LVD patients only. When the data was
      stratified based on age and sex, a statistically significant association was
      observed for ACE 'II' genotype (OR = 2.288; p = 0.006) and 'I' allele (OR =
      1.395; p = 0.054) in IS male patients of > 50 years of age. The ACE 'D' allele
      was found to be increased in controls (OR = 0.709; p = 0.018) than IS patients.
      Multivariate logistic regression analysis showed that smoking and diabetes were
      the most powerful independent risk factor in LVD type of stroke. Thus, we
      presented here an evidence for a strong association of ACE 'II' genotype and 'I'
      allele compounded by factors such as smoking and diabetes among south Indian IS
      patients. 

PMID- 25606451
TI  - At the southeast fringe of the Bantu expansion: genetic diversity and
      phylogenetic relationships to other sub-Saharan tribes.
AB  - Here, we present 12 loci paternal haplotypes (Y-STR profiles) against the
      backdrop of the Y-SNP marker system of Bantu males from the Maputo Province of
      Southeast Africa, a region believed to represent the southeastern fringe of the
      Bantu expansion. Our Maputo Bantu group was analyzed within the context of 27
      geographically relevant reference populations in order to ascertain its genetic
      relationship to other Bantu and non Bantu (Pygmy, Khoisan and Nilotic) sub
      equatorial tribes from West and East Africa. This study entails statistical pair
      wise comparisons and multidimensional scaling based on YSTR Rst distances,
      network analyses of Bantu (B2a-M150) and Pygmy (B2b-M112) lineages as well as an
      assessment of Y-SNP distribution patterns. Several notable findings include the
      following: 1) the Maputo Province Bantu exhibits a relatively close paternal
      affinity with both east and west Bantu tribes due to high proportion of Bantu Y
      chromosomal markers, 2) only traces of Khoisan (1.3%) and Pygmy (1.3%) markers
      persist in the Maputo Province Bantu gene pool, 3) the occurrence of R1a1a
      M17/M198, a member of the Eurasian R1a-M420 branch in the population of the
      Maputo Province, may represent back migration events and/or recent admixture
      events, 4) the shared presence of E1b1b1-M35 in all Tanzanian tribes examined,
      including Bantu and non-Bantu groups, in conjunction with its nearly complete
      absence in the West African populations indicate that, in addition to a shared
      linguistic, cultural and genetic heritage, geography (e.g., east vs. west) may
      have impacted the paternal landscape of sub-Saharan Africa, 5) the admixture and
      assimilation processes of Bantu elements were both highly complex and region
      specific. 

PMID- 25606452
TI  - Genetic polymorphism of the human organic solute carrier protein 1 (hOSCP1) gene
      in Japanese patients with non-viral liver carcinoma.
AB  - Human organic solute carrier protein 1 (hOSCP1) is a Na(+)-independent
      multispecific organic solute transporter. To date, several studies have revealed
      that gene mutations of the transporters are likely to be associated with some
      diseases; however, there are no data concerning the genetic polymorphism of the
      hOSCP1 gene in Japanese patients with non-viral liver carcinoma (LC). In the
      present study, we isolated genomic DNA from a normal portion of LC, and analyzed
      41 single nucleotide polymorphisms (SNPs) chosen from a database of SNPs
      (dbSNPs). We found genotype frequencies for 2 non-synonymous SNPs [rs34409118
      (Thr(131) -> Ala) and rs1416840 (Ile(219) -> Thr)] and 1 synonymous SNP
      [rs16822954 (Ser(193) -> Ser)] to be statistically significant when compared with
      dbSNPs. No statistical significance was observed in rs2275477 (Gly(307) -> Arg)
      in the hOSCP1 gene. With respect to the allele frequency, we also observed
      rs34409118 to be statistically significant. Interestingly, we found that non
      viral LC patients do not carry heterozygous mutations in rs1416840 (A/G) and
      rs16822954 (A/G), suggesting that a non-carrier of heterozygous mutations in
      these two SNPs might be a biomarker for susceptibility for non-viral LC in
      Japanese. Further analyses of patients with hOSCP1 variants may elucidate the
      relationship between the hOSCP1 gene and susceptibility of non-viral LC in
      Japanese patients. 

PMID- 25606453
TI  - In- silico exploration of thirty alphavirus genomes for analysis of the simple
      sequence repeats.
AB  - The compilation of simple sequence repeats (SSRs) in viruses and its analysis
      with reference to incidence, distribution and variation would be instrumental in
      understanding the functional and evolutionary aspects of repeat sequences.
      Present study encompasses the analysis of SSRs across 30 species of alphaviruses.
      The full length genome sequences, assessed from NCBI were used for extraction and
      analysis of repeat sequences using IMEx software. The repeats of different motif
      sizes (mono- to penta-nucleotide) observed therein exhibited variable incidence
      across the species. Expectedly, mononucleotide A/T was the most prevalent
      followed by dinucleotide AG/GA and trinucleotide AAG/GAA in these genomes. The
      conversion of SSRs to imperfect microsatellite or compound microsatellite (cSSR)
      is low. cSSR, primarily constituted by variant motifs accounted for up to 12.5%
      of the SSRs. Interestingly, seven species lacked cSSR in their genomes. However,
      the SSR and cSSR are predominantly localized to the coding region ORFs for non
      structural protein and structural proteins. The relative frequencies of different
      classes of simple and compound microsatellites within and across genomes have
      been highlighted. 

PMID- 25606454
TI  - High gene flow and genetic diversity in three economically important Zanthoxylum
      Spp. of Upper Brahmaputra Valley Zone of NE India using molecular markers.
AB  - The genetic diversity in Zanthoxylum species viz.  Zanthoxylum nitidum,
      Zanthoxylum oxyphyllum and Zanthoxylum rhesta collected from the Upper
      Brahmaputra Valley Zone of Assam (NE India) was amplified using 13 random
      amplified polymorphic DNA (RAPD) markers and 9 inter-simple sequence repeat
      (ISSR) markers. RAPD markers were able to detect 81.82% polymorphism whereas ISSR
      detected 98.02% polymorphism. The genetic similarities were analyzed from the
      dendrogram constructed by RAPD and ISSR fingerprinting methods which divided the
      3 species of Zanthoxylum into 3 clear different clusters. The principle component
      analysis (PCA) was carried out to confirm the clustering pattern of RAPD and ISSR
      analysis. Analysis of molecular variance (AMOVA) revealed the presence of
      significant variability between different Zanthoxylum species and within the
      species by both RAPD and ISSR markers. Z. nitidum was found to be sharing a high
      degree of variation with the other two Zanthoxylum species under study. The Nei's
      gene diversity (h), Shannon's information index (I), observed number of alleles
      (na) and effective number of alleles (ne) were also found to be higher in ISSR
      markers (0.3526, 0.5230, 1.9802 and 1.6145) than in RAPD markers (0.3144, 0.4610,
      1.8182 and 1.5571). The values for total genotype diversity for among population
      (HT), within population diversity (Hs) and gene flow (Nm) were more in ISSR
      (0.3491, 0.2644 and 1.5610) than RAPD (0.3128, 0.2264 and 1.3087) but the mean
      coefficient of gene differentiation (GST) was more in RAPD (0.2764) than ISSR
      (0.2426). A comparison of this two finger printing methods was done by
      calculating MR, EMI and MI. The correlation coefficient between data matrices of
      RAPD and ISSR based on Mantel test was found to be significant (r = 0.65612). 

PMID- 25606455
TI  - Lack of association between glutathione peroxidase1 (GPx1) activity, Pro198Leu
      polymorphism and stenosis of coronary arteries: A population-based prediction.
AB  - BACKGROUND: We studied the association between erythrocyte glutathione
      peroxidase1 (GPx1) activity and rs1050450 (Pro198Leu) site with the stenosis of
      coronary arteries and, evaluated the Pro/Leu position within the predicted
      tertiary structure. METHODS: Subjects were recruited from who underwent coronary
      angiography (controls; n = 55, Stenosis < 5% and Patients; n = 95, Stenosis >=
      50%). The GPx1 activity and rs1050450 C/T variants were determined using enzyme
      assay and RFLP-PCR techniques, respectively. The conserved regions and GPx1
      tertiary structure were predicted using bioinformatics tools. RESULTS: We did not
      find significant association between GPx1 activity (P = 0.96), rs1050450 genotype
      distribution and coronary artery disease (adjusted OR = 0.79; 95%CI 0.28-2.2, P =
      0.6). The polymorphic variants were not located at the predicted structural and
      functional domains so that it had not the significant role on the GPx1stability
      and function. CONCLUSIONS: In agreement with the results predicted from
      bioinformatics tools, we suggested that the GPx1 activity and rs1050450
      (Pro198Leu) site are not involved in the development of stenosis of coronary
      arteries in the study population.

PMID- 25606456
TI  - KIR genotype distribution among patients with multiple myeloma: Higher prevalence
      of KIR 2DS4 and KIR 2DS5 genes.
AB  - INTRODUCTION: Natural killer (NK) cells possess an antitumor activity against
      multiple myeloma cells proven by the susceptibility of plasmocytes to NK lysis.
      In the early stage of MM, the killing of MM cells is mediated by natural
      cytotoxicity receptors (NRC) and NKG2D-dependent pathway, while in the late
      stage, NK cells lose their killing potential against MM cells due to the high
      expression of HLA class I molecules on MM cells. AIM: The aim of this paper is to
      study KIR expression of NK cells in MM patients and in healthy controls, to check
      for any association between KIR genotypes and MM. METHODS: KIR genotype was
      analyzed in 120 healthy Lebanese individuals and 34 MM patients using the KIR
      Genotyping SSP kit. RESULTS: KIR 2DS4*001/002 and KIR 2DS5 were found to be
      significantly more prevalent among MM patients as compared to controls. For MM
      patients, the AA, AB, and BB genotype frequencies were, respectively, 38.23%,
      47.06% and 14.71% with an A:B ratio of 1.62:1. As for the healthy controls, the
      AA, AB, and BB genotype frequencies were, respectively, 39.17%, 50%, and 10.83%
      with an A:B ratio of 1.80:1. CONCLUSION: The interesting observation of the
      significant presence of KIR2DS4 and KIR2DS5 genes more among multiple myeloma
      patients than controls is worth further clinical, translational as well as
      survival research studies in these cases.

PMID- 25606457
TI  - DNA barcoding of Pentatomomorpha bugs (Hemiptera: Heteroptera) from Western Ghats
      of India.
AB  - Recent studies from East Asia and Canadian National Collection of Insects have
      established the utility of DNA barcoding technique in identification of true
      bugs. The present study is an expansion of the database by adding mitochondrial
      cytochrome c oxidase I (mtCOI) sequences from forty three species of indigenous
      true bugs of India. mtCOI gene analysis of infraorder Pentatomomorpha covering a
      total of seventy three species that belong to five superfamilies; Pentatomoidea,
      Coreoidea, Pyrrhocoroidea, Lygaeoidea and Aradoidea revealed more than 3%
      interspecific distances in all the taxa studied except for two cases which showed
      barcode sharing. Less than 2% intra-specific divergence was observed in 97% of
      the taxa analysed and the average interspecies genetic distance was about 29
      times higher than the average intraspecies genetic divergence. Distinct sequence
      divergence pattern at generic level and NJ clustering analysis suggests that COI
      barcode is an excellent molecular marker for species level identification of
      unknown taxa; however it may not be useful for resolving deep levels of
      divergence. Species identification even at nymphal stage could be achieved
      confirming the efficacy of this technique. 

PMID- 25606459
TI  - The reduction of vascular disease risk mutations contributes to longevity in the
      Chinese population.
AB  - AIM: Genetic factors play important roles in determining human lifespan. Although
      some "longevity genes" have been identified to be implicated in human longevity,
      many disease-associated variants were also observed in the long-lived
      individuals. The oldest old and their offspring usually have a lower prevalence
      of age-related diseases, which is likely attributed to a reduction or an absence
      of disease risk variants. METHODS AND RESULTS: To test this hypothesis, 23
      disease risk single nucleotide polymorphisms (SNPs), identified by previous
      genome-wide association studies (GWASs), were selected and genotyped in 1074
      samples consisting of 574 longevity subjects (over 90 years old) and 500 younger
      controls. Our results revealed that 5 SNPs (rs2144300, rs1864163, rs2200733,
      rs1967017, and rs7193343) displayed significantly lower allelic frequencies and
      odds ratios (ORs) in the longevity group than that in the control group. The
      frequencies of homozygous mutation genotypes and corresponding ORs of the
      rs1864163, rs2200733, rs127430, rs1967017, and rs12413409 were lower in the
      longevity subjects. Interestingly, most of the abovementioned SNPs convey
      susceptibility to cardiovascular disease (CVD), which is the leading cause of
      deaths in old adults but shows a much lower incidence in the longevity
      individuals and their offspring. CONCLUSION: Taking into account the observation
      that the longevity subjects and their offspring have lower rate of cardiovascular
      mortality, it is then most plausible that the lack of disease risk variants,
      especially the CVD, is a genetic contributor to longevity in the Chinese
      population.

PMID- 25606458
TI  - Characterization of the bovine gene LIPE and possible influence on fatty acid
      composition of meat.
AB  - LIPE is an intracellular neutral lipase, which is capable of hydrolyzing a
      variety of esters and plays a key role in the mobilization of fatty acids from
      diacylglycerols. The objectives of this study were to characterize the genetic
      polymorphism of bovine LIPE gene and to evaluate the possible association between
      three SNPs in the coding regions of this gene with the fatty acid composition of
      meat in a cattle population. Forty-three unrelated animals from different cattle
      breeds were re-sequenced and 21 SNPs were detected over approximately 2600 bp,
      five of these SNPs were novel. Three SNPs were selected, on the basis of
      evolutionary conservation, to perform validation and association studies in a
      crossbred cattle population. Our results may suggest a possible association of
      SNP1 with contents of oleic acid and total monounsaturated fatty acids (p <
      0.01), and SNP2 and SNP3 with Heneicosylic acid content (p < 0.01), may be
      helpful to improve the quality of meat and improve health. 

PMID- 25606460
TI  - Analysis of genetic variations across regulatory and coding regions of kappa
      casein gene of Indian native cattle (Bos indicus) and buffalo (Bubalus bubalis).
AB  - The promoter region of kappa-casein (kappa-CN) gene in Indian native cattle and
      buffalo breeds was sequenced and analyzed for nucleotide variations. Sequence
      comparison across breeds of Indian cattle revealed a total of 7 variations in the
      promoter region, of which - 515 G/T, - 427 C/T, - 385 C/T, - 283 A/G and - 251
      C/T were located within consensus binding sites for octamer-binding protein
      (OCT1)/pregnancy specific mammary nuclear factor (PMF), activator protein-2
      (AP2), hepatocyte nuclear factor (HNF-1) and GAL4 transcription factors (TFs),
      respectively. These variations might be involved in gain or loss of potential
      transcription factor binding sites (TFBSs). Unlike the other 4 variants, the -
      283 (A/G) variant located within HNF-1 TFBS was specific to Indian cattle as this
      change has not been observed in the Bos taurus sequence. Other TFBSs viz., MGF,
      TBP, NF-1, milk box and C/EBP were conserved across species. For the Indian
      native buffalo breeds, only 3 changes were identified in the promoter region; -
      305 (A/C), - 160 (T/C) and - 141 (A/G) and most of the TFBSs were found to be
      conserved. However, deletion of two adjacent nucleotides located in and around
      binding site for C/EBP TF was identified in buffalo when compared with promoter
      sequence of bovine kappa-CN. For kappa-CN of Indian native cattle, a strong
      linkage disequilibrium (LD) was observed for variations 515 G/T, - 427 C/T and -
      385 C/T in the promoter region; and for variations at codons 136 and 148 of exon
      IV. Further, among intragenic haplotypes, variation - 427 C/T was found to be in
      LD with variations at codons 136 and 148. The information generated in the
      present work provides comprehensive characterization of kappa-CN gene promoter
      and coding regions in Indian cattle and buffaloes and reported variations could
      become important candidates for carrying out further research in dairy traits. 

PMID- 25606461
TI  - Comparative in-silico genome analysis of Leishmania (Leishmania) donovani: A step
      towards its species specificity.
AB  - Comparative genome analysis of recently sequenced Leishmania (L.) donovani was
      unexplored so far. The present study deals with the complete scanning of L. (L.)
      donovani genome revealing its interspecies variations. 60 distinctly present
      genes in L. (L.) donovani were identified when the whole genome was compared with
      Leishmania (L.) infantum. Similarly 72, 159, and 265 species specific genes were
      identified in L. (L.) donovani when compared to Leishmania (L.) major, Leishmania
      (L.) mexicana and Leishmania (Viannia) braziliensis respectively. The cross
      comparison of L. (L.) donovani in parallel with the other sequenced species of
      leishmanial led to the identification of 55 genes which are highly specific and
      expressed exclusively in L. (L.) donovani. We found mainly the discrepancies of
      surface proteins such as amastins, proteases, and peptidases. Also 415 repeat
      containing proteins in L. (L.) donovani and their differential distribution in
      other leishmanial species were identified which might have a potential role
      during pathogenesis. The genes identified can be evaluated as drug targets for
      anti-leishmanial treatment, exploring the scope for extensive future
      investigations. 

PMID- 25606462
TI  - 19q13.33->qter trisomy in a girl with intellectual impairment and seizures.
AB  - Rearrangements in chromosome 19 are rare. Among the 35 patients with partial 19q
      trisomy described, only six have a breakpoint defined by array. The 19q
      duplication results in a variable phenotype, including dysmorphisms, intellectual
      disability and seizure. In a female patient, although G-banding at 550 band
      resolution was normal, multiplex ligation-dependent probe amplification (MLPA)
      technique and genomic array showed a 10.6 Mb terminal duplication of chromosome
      19q13. Fluorescent in situ hybridization (FISH) revealed that the duplicated
      region was attached to the short arm of chromosome 21 and silver staining showed
      four small acrocentrics with nucleolar organization region (NOR) activity,
      suggesting that the breakpoint in chromosome 21 was at p13. This is the first de
      novo translocation between 19q13.33 and 21p13 described in liveborn. The
      chromosome 19 is known to be rich in coding and non-coding regions, and
      chromosomal rearrangements involving this chromosome are very harmful.
      Furthermore, the 19q13.33->qter region is dense in pseudogenes and microRNAs,
      which are potent regulators of gene expression. The trisomic level of this region
      may contribute to deregulation of global gene expression, and consequently, may
      lead to abnormal development on the carriers of these rearrangements. 

PMID- 25606463
TI  - CTAB-mediated, single-step preparation of competent Escherichia coli,
      Bifidobacterium sp. and Kluyveromyces lactis cells.
AB  - An efficient and reproducible method for transformation depends on the competency
      of the organism. We have developed a simple method for the preparation of
      competent Escherichia coli, Kluyveromyces lactis, and Bifidobacterium sp. by
      using a buffer containing cetyl trimethyl ammonium bromide (CTAB) and permits
      efficient uptake of plasmid DNA and ligation-reaction products. Cells are
      harvested, washed, mixed with 1-10 MUg/ml CTAB, incubated, and followed by a
      buffer wash. For long-term storage of competent cells, bacteria may be frozen in
      10% glycerol without the addition of other components. The transformation process
      is very simple; plasmid DNA and the cells are mixed and incubated for 5-60 min at
      4  degrees C; no heat pulse is required, and the duration of incubation at 4 
      degrees C is not crucial. 

PMID- 25606464
TI  - let-65 is cytoplasmic methionyl tRNA synthetase in C. elegans.
AB  - Cytoplasmic methionyl tRNA synthetase (MetRS) is one of more than 20 cytoplasmic
      aminoacyl tRNA synthetase enzymes (ARS). This family of enzymes catalyzes a
      process fundamental for protein translation. Using a combination of genetic
      mapping, oligonucleotide array comparative genomic hybridization, and phenotypic
      correlation, we show that mutations in the essential gene, let-65, reside within
      the predicted Caenorhabditis elegans homologue of MetRS, which we have named mars
      1. We demonstrate that the lethality associated with alleles of let-65 is fully
      rescued by a transgenic array that spans the mars-1 genomic region. Furthermore,
      sequence analysis reveals that six let-65 alleles lead to the alteration of
      highly conserved amino acids. 

PMID- 25606465
TI  - Androgen receptor and monoamine oxidase polymorphism in wild bonobos.
AB  - Androgen receptor gene (AR), monoamine oxidase A gene (MAOA) and monoamine
      oxidase B gene (MAOB) have been found to have associations with behavioral
      traits, such as aggressiveness, and disorders in humans. However, the extent to
      which similar genetic effects might influence the behavior of wild apes is
      unclear. We examined the loci AR glutamine repeat (ARQ), AR glycine repeat (ARG),
      MAOA intron 2 dinucleotide repeat (MAin2) and MAOB intron 2 dinucleotide repeat
      (MBin2) in 32 wild bonobos, Pan paniscus, and compared them with those of
      chimpanzees, Pan troglodytes, and humans. We found that bonobos were polymorphic
      on the four loci examined. Both loci MAin2 and MBin2 in bonobos showed a higher
      diversity than in chimpanzees. Because monoamine oxidase influences
      aggressiveness, the differences between the polymorphisms of MAin2 and MBin2 in
      bonobos and chimpanzees may be associated with the differences in aggression
      between the two species. In order to understand the evolution of these loci and
      AR, MAOA and MAOB in humans and non-human primates, it would be useful to conduct
      future studies focusing on the potential association between aggressiveness, and
      other personality traits, and polymorphisms documented in bonobos. 

PMID- 25606466
TI  - Genes and personality characteristics: Possible association of the genetic
      background with intelligence and decision making in 830 Caucasian Greek subjects.
AB  - It is well known that intelligence consists of a variety of interactional and
      cognitive skills and abilities (e.g. tradecraft; critical and divergent thinking;
      perception of foreign information). Decision making is defined as the conscious
      choice between given options, relating to a problem. Both genetic background and
      environment comprise key elements for personality characteristics of the human
      being. The aim of this study is to determine the frequency distribution of
      rs324420, rs1800497, rs363050, rs6265, rs1328674 polymorphisms known to be
      involved in individual personality characteristics, in 830 Greek Subjects. The
      study is independent from direct clinical measurements (e.g. IQ measurements;
      physiological tests). The population of the volunteers is described, based on
      genotype, sex, with the respective gene frequencies, including the Minor Allele
      Frequency (MAF). A potential influence of the volunteer gender with the above
      characteristics (based on genotypes and alleles) is examined and finally,
      volunteers are classified as follows: A volunteer receives + 1, for each
      genotype/allele, which enhances his intelligence or his decision-making. In
      contrast, he receives - 1, for each genotype/allele, which relegates the
      individual characteristic. No statistically significant gender-characteristics
      correlation is observed. According to their genetic profile, a rate of 92.5%, of
      the volunteers may be characterized by prudence and temperance of thought, with
      only a small proportion of them (7.5%) may be classified as genetically
      spontaneous and adventurous. Regarding intelligence, the study population may lay
      around average and a little above it, at a rate of 96.3%, while the edges of the
      scale suggest only a 0.5% of the volunteers, who, although the "smartest",
      somehow seem to lack prudence. In conclusion, individuals with low cognitive
      ability may be more prudent than others and vice versa, while the "smartest" ones
      tend to be more risky, in decision-making. Therefore, intelligence and decision
      making may, after all, be less linked to each other than expected. 

PMID- 25606467
TI  - Cloning and comparative analysis of gene structure in promoter site of alpha-s1
      casein gene in Naeinian goat and sheep.
AB  - The 5' end or alpha-S1 casein promoter has a significant role in milk protein
      gene expression. The understanding of the translation process of alpha-S1 casein
      mutants will provide us an opportunity to make the best selection in livestock
      providing more proteins in milk. Blood samples were taken from three hundred of
      Naeinian goats and sheep, and DNA extraction was done using modified salting out
      method. Polymerase chain reactions (PCR) were carried out using a specific primer
      pairs for amplification a fragment of 1133 bp from part of 5'-UTR and exon 1 of
      alpha s1 casein gene. The AluI and HinfI restriction enzyme treatment of all
      samples provided the same homozygous AA genotype in both species. Subsequently,
      one sample of each species was selected and cloned, and the final sequences were
      analyzed by BioEdit, CLC genomic, Mega4 and DNASIS MAX software. Several
      polymorphisms are recognized between Naeinian goat and sheep that are presented
      on motif sites. In this research, the interested location, including exon I and a
      part of 5', was analyzed, and genetic element comparisons were done between
      Naeinian goat and sheep. The number and location of probable binding sites can
      have a crucial role as a result of antagonistic and synergistic effects on gene
      regulation activities. 

PMID- 25606468
TI  - Southeast Asian mouth-brooding Betta fighting fish (Teleostei: Perciformes)
      species and their phylogenetic relationships based on mitochondrial COI and
      nuclear ITS1 DNA sequences and analyses.
AB  - Fighting fish species in the genus Betta are found in several Southeast Asian
      countries. Depending on the mode of paternal care for fertilized eggs and
      hatchlings, various species of the betta fish are classified as mouth brooders or
      nest builders whose members in turn have been grouped according to their
      similarities mainly in morphology. The mouth brooders as well as some nest
      builders involved in the present study include fishes discovered and identified
      subsequent to previous reports on species groupings and their positions on
      phylogenetic trees based on DNA sequences that differ from those used by us in
      this study. From the mitochondrial COI gene and nuclear ITS1 gene sequences and
      more accurate analyses we conclude that the following members of the mouth
      brooding pairs, named differently previously, are virtually identical, viz the
      Betta prima-Betta pallida pair and Betta ferox-Betta apollon pair. The Betta
      simplex, hitherto believed to be one species, could possibly be genetically split
      into 2 distinct species. In addition, several other established type-locality
      fishes could harbor cryptic species as judged by genetic differences. Assignments
      of fish species to groups reported earlier may have to be altered somewhat by the
      present genetic findings. We propose here a new Betta fish phylogenetic tree
      which, albeit being similar to the previous ones, is clearly different from them.
      Our gene-based evidence also leads to assignments of some fishes to new species
      groups and alters the positions of some species on the new phylogenetic tree,
      thus implying different ancestral relationships. 

PMID- 25606469
TI  - A novel GLI3c.750delC truncation mutation in a multiplex Greig
      cephalopolysyndactyly syndrome family with an unusual phenotypic combination in a
      patient.
AB  - Greig cephalopolysyndactyly (GCPS) syndrome is an autosomal dominant disorder
      with high penetrance in majority of cases, characterized by a triad of
      polysyndactyly, macrocephaly and hypertelorism. GCPS is known to be caused by
      mutations in the transcription factor GLI3 gene (7p13) which results in
      functional haploinsufficiency of this gene. The present study reports a large
      multiplex family having 12 members affected with GCPS in 3 generations and
      several unaffected members showing autosomal dominant pattern of inheritance with
      complete penetrance. Interestingly an affected member of the family had unusual
      features including thumb which is although biphalangeal (confirmed with X-ray)
      but morphologically looks like finger and a unilateral tiny bony outgrown
      (externally indistinguishable) on the distal phalanx of the first toe of the left
      foot. This member also presented with mild ichthyosis. Although it is also
      possible that one or more of these features are coincidentally present in this
      member and might not be part of GCPS. Resequencing of the GLI3 gene detected a
      novel frame-shift mutation c.750delC in heterozygous state transmitting in the
      family and co-segregating with the disorder suggesting it to be the causal for
      the GCPS phenotype in the family. In silico analysis suggests that this mutation
      creates a truncated GLI3 protein resulting in its haploinsufficiency leading to
      GCPS syndrome. Furthermore, genotype-phenotype correlation is supported by the
      mutation as it lies in the amino terminal domain of the protein. 

PMID- 25606470
TI  - Regenerative potential of endometrial stem cells: a mini review.
AB  - Recent findings in stem cell biology have opened a new window in regenerative
      medicine. The endometrium possesses mesenchymal stem cells (MSCs) called
      endometrial stem cells (EnSCs) having specific regenerative properties linked to
      adult stem cells. They contribute in tissue remodeling and engineering and were
      shown to have immuno-modulating effects. Many clinical trials were undertaken to
      ascertain the therapeutic potential of EnSCS. In this mini review, we showed that
      EnSCs are readily available sources of adult stem cells in the uterus that can be
      highlighted for their renewable multipotent and differentiation properties. This
      cell population may be a practical solution of choice in reproductive biology,
      regenerative medicine and autologous stem cell therapy. 

PMID- 25606471
TI  - Burn wound infections and antibiotic susceptibility patterns at pakistan
      institute of medical sciences, islamabad, pakistan.
AB  - BACKGROND: Burn wound infections carry considerable mortality and morbidity
      amongst burn injury victims who have been successfully rescued through the
      initial resuscitation. This study assessed the prevalent microrganisms causing
      burn wound infections among hospitalized patients; their susceptibility pattern
      to commonly used antibiotics; and the frequency of infections with respect to the
      duration of the burn wounds. METHODS: This study was carried out at Burn Care
      Centre, Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan over a
      period of two years (i.e. from June 2010 to May 2012). The study included all
      wound-culture-positive patients of either gender and all ages, who had sustained
      deep burns and underwent definitive management with wound excisions and skin auto
      grafting. Patients with negative cultures of the wounds were excluded. Tissue
      specimens for culture and sensitivity were collected from burn wounds using
      standard collection techniques and analyzed at microbiological laboratory.
      RESULTS: Out of a total of 95 positive microbial growths, 36 were Pseudomonas
      aeruginosa (35.29%) as the most frequent isolate found, followed by 21 Klebsiella
      pneumoniae (20.58%), 19 Staphylococcus aureaus (18.62%), 10 Proteus (9.80%), 7 E.
      coli (6.86%), 7 Acinetobacter (6.86%), and 4 Candida (3.92%). A variable
      antibiotic susceptibility pattern was observed among the grown microbes. Positive
      cultures were significantly more frequent among patients with over two weeks
      duration of burn wounds. CONCLUSION: P. aeruginosa, K. pneumoniae and S. aureus
      constituted the most common bacterial microbes of burn wounds in our in-patients
      cases. Positive cultures were more frequent among patients with over two weeks
      duration of burn wounds. Early excision and skin grafting of deep burns and
      adherence to infection control measures can help to effectively reduce the burden
      of these infections.

PMID- 25606472
TI  - The healing effect of scrophularia striata on experimental burn wounds infected
      to pseudomonas aeruginosa in rat.
AB  - BACKGROUND: The cause of death in burn patients after 48 hours of hospitalization
      has been reported to be bacterial infections. Recently, due to the compounds
      accelerating the healing process and the intense reduction of treatment side
      effects, medicinal plants are used to cure burn wound infections. This study aims
      to investigate the medicinal effect of the ethanolic extract of Scrophularia
      striata on burn wound infection in in-vivo and in-vitro in comparison with silver
      sulfadiazine (SSD). METHODS: One hundred and fifty male Sprague Dawley rats were
      divided into 3 equal groups. A hot plate of 1*1cm was used to create second
      degree burn wounds. The ethanolic extract of S. striata was provided through
      percolation method. Group 1 was treated with SSD, group 2 with S. striata, and
      group 3 was considered as control group. All animals were infected to Pseudomonas
      aeruginosa. On days 3, 7, 10, 14, and 21 after burn wound injury, the animals
      were euthanized and were evaluated histologically. The MIC and MBC were
      determined using the micro dilution method. RESULTS: The rate of wound healing
      was significantly greater in S. striata group in comparison to SSD and control
      groups. CONCLUSION: S. striata contains was shown to have anti-bacterial and
      wound healing effects while this effect was significantly more than SSD denoting
      to its use when needed for burn wounds infected to P. aeruginosa.

PMID- 25606473
TI  - The healing effect of nettle extract on second degree burn wounds.
AB  - BACKGROUND: Numerous studies were carried out to develop more sophisticated
      dressings to expedite healing processes and diminish the bacterial burden in burn
      wounds. This study assessed the healing effect of nettle extract on second degree
      burns wound in rats in comparison with silver sulfadiazine and vaseline. METHODS:
      Forty rats were randomly assigned to four equal groups. A deep second-degree burn
      was created on the back of each rat using a standard burning procedure. The burns
      were dressed daily with nettle extract in group 1, silver sulfadiazine in group
      2, vaseline in group 3 and without any medication in group 4 as control group.
      The response to treatment was assessed by digital photography during the
      treatment until day 42. Histological scoring was undertaken for scar tissue
      samples on days 10 and 42. RESULTS: A statistically significant difference was
      observed in group 1 compared with other groups regarding 4 scoring parameters
      after 10 days. A statistically significant difference was seen for fibrosis
      parameter after 42 days. In terms of difference of wound surface area, maximal
      healing was noticed at the same time in nettle group and minimal repair in the
      control group. CONCLUSION: Our findings showed maximal rate of healing in the
      nettle group. So it may be a suitable substitute for silver sulfadiazine and
      vaseline when available.

PMID- 25606475
TI  - The effect of shiatsu massage on underlying anxiety in burn patients.
AB  - BACKGROUND: Burn patients experience high levels of predictable anxiety during
      dressing changes while anti-anxiety drugs cannot control these anxieties. The
      nurses can limit the side effects of medications by undertaking complementary
      therapies. Hand pressure massage was introduced as a technique that can reduce
      these anxieties. This study aimed to investigate the effect of hand pressure
      massage using Shiatsu method on underlying anxiety in burn patients. METHODS: In
      an available randomized study, 60 burn patients with underlying pain were
      enrolled. They were randomly allocated in two groups of hand massage and the
      control. The anxiety of underlying burn pain before and after the massage was
      evaluated using Burn Specific Pain Anxiety Scale (BSPAS). RESULTS: The difference
      for anxiety scores in the hand Shiatsu massage group before and after massage
      were statistically significant, but in the control group was not significant.
      CONCLUSION: Based on our findings, 20 minutes of hand Shiatsu massage in
      conjunction with analgesic medications can be beneficial to control the anxiety
      of burn patients.

PMID- 25606474
TI  - The healing effect of curcumin on burn wounds in rat.
AB  - BACKGROUND: Burns are still considered one of the most devastating conditions in
      emergency medicine affecting both genders and all age groups in developed and
      developing countries, resulting into physical and psychological scars and cause
      chronic disabilities. This study was performed to determine the healing effect of
      curcumin on burn wounds in rat. METHODS: Seventy female Sprague-Dawley 180-220 g
      rats were randomly divided into 5 equal groups. Groups of A-C received 0.1, 0.5
      and 2% curcumin respectively and Group D, silver sulfadiazine ointment. Group E
      was considered as control group and received eucerin. After 7, 14 and 21 days of
      therapy, the animals were sacrificed and burn areas were macroscopically examined
      and histologically were scored. RESULTS: Administration of curcumin resulted into
      a decrease in size of the burn wounds and a reduction in inflammation after
      14(th) days. Reepithelialization was prominent in groups A-C while more
      distinguishable in group C. In group C, epidermis exhibited well structured
      layers without any crusting. There were spindle shaped fibroblasts in fascicular
      pattern, oriented parallel to the epithelial surface with eosinophilic collagen
      matrix. CONCLUSION: Curcumin as an available and inexpensive herbal was shown be
      a suitable substitute in healing of burn wounds especially when 2% concentration
      was applied.

PMID- 25606476
TI  - Reconstructive surgery of extensive face and neck burn scars using tissue
      expanders.
AB  - BACKGROUND: Neck reconstruction is considered as one of the most important
      surgeries in cosmetic and reconstructive surgery. The present study aimed to
      assess the results of reconstructive surgery of extensive face and neck burning
      scars using tissue expanders. METHODS: This descriptive prospective study was
      conducted on 36 patients with extensive burning scars on the neck and face.
      Operation for tissue expander insertion was performed and tissue distension
      started two or three weeks later, depending on the patients' incisions. After
      sufficient time for tissue expansion, while removing the expander and excision of
      the lesion, the expanded flap was used to cover the lesion. Overall, 43 cosmetic
      surgeries were done. RESULTS: Rectangular expanders were employed in most
      patients (73.81%) and were located in the neck in most of them (60.78%).
      Complications were detected in five patients (13.89%), with exposure of the
      prosthesis being the most common one. Scar tissues at the reconstruction site and
      the flap donor site were acceptable in 94.44% and 98.18% of the cases,
      respectively. Overall, most of the patients (77.78%) were satisfied with the
      operation results.  CONCLUSION: Using tissue expanders in tissue reconstruction
      of extensive neck and facial burning scars results in highly desirable outcomes.

PMID- 25606477
TI  - Comparison between Conventional Mechanical Fixation and Use of Autologous
      Platelet Rich Plasma (PRP) in Wound Beds Prior to Resurfacing with Split
      Thickness Skin Graft.
AB  - BACKGROUND: Platelet rich plasma is known for its hemostatic, adhesive and
      healing properties in view of the multiple growth factors released from the
      platelets to the site of wound. The primary objective of this study was to use
      autologous platelet rich plasma (PRP) in wound beds for anchorage of skin grafts
      instead of conventional methods like sutures, staplers or glue. METHODS: In a
      single center based randomized controlled prospective study of nine months
      duration, 200 patients with wounds were divided into two equal groups. Autologous
      PRP was applied on wound beds in PRP group and conventional methods like
      staples/sutures used to anchor the skin grafts in a control group. RESULTS:
      Instant graft adherence to wound bed was statistically significant in the PRP
      group. Time of first post-graft inspection was delayed, and hematoma, graft
      edema, discharge from graft site, frequency of dressings and duration of stay in
      plastic surgery unit were significantly less in the PRP group. CONCLUSION:
      Autologous PRP ensured instant skin graft adherence to wound bed in comparison to
      conventional methods of anchorage. Hence, we recommend the use of autologous PRP
      routinely on wounds prior to resurfacing to ensure the benefits of early healing.

PMID- 25606478
TI  - Comparison of effects of labetalol and nitroglycerine on intraoperative blood
      loss and surgical field quality in rhinoplasty surgery.
AB  - BACKGROUND: Rhinoplasty is one of the most common surgeries of the plastic
      surgery and as well as ear, throat and nose. Intra-operative bleeding during
      surgery is one of the most important factors that may impair the surgeon's job.
      Providing a clean blood-free surgical filed makes the operation faster, easier
      and with a better quality. One way to achieve this goal is to induce hypotension.
      This study aimed to compare the impacts and outcomes of administration of
      labetalol or nitroglycerin for this purpose. METHODS: In this randomized clinical
      trial, 60 ASA I and ASA II patients who were referred for rhinoplasty were
      enrolled. Patients were randomly assigned to two groups. Labetalol was given to
      the first and nitroglycerin to the second group of patients. Blood pressure and
      the amount of intra-operative bleeding during surgery and surgeon satisfaction
      were measured. RESULTS: The average age of patients was 25.9+/-7.52 years. The
      average amount of bleeding among all patients was 117.87+/-324.86 ml, and the
      average quality of the surgical site was 1.65+/-4.48, considering all patients.
      The average quality and average surgical site bleeding between the two groups was
      not significant. CONCLUSION: There was a little difference between labetalol and
      nitroglycerine on the effect of intraoperative blood loss and surgical field
      quality in rhinoplasty surgery.

PMID- 25606479
TI  - The Healing Effects of Aquatic Activities and Allogenic Injection of Platelet
      Rich Plasma (PRP) on Injuries of Achilles Tendon in Experimental Rat.
AB  - BACKGROUND: Clinical tendon injuries represent serious and unresolved issues of
      the case on how the injured tendons could be improved based on natural structure
      and mechanical strength. The aim of this studies the effect of aquatic activities
      and alogenic platelet rich plasma (PRP) injection in healing Achilles tendons of
      rats. METHODS: Forty rats were randomly divided into 5 equal groups. Seventy two
      hours after a crush lesion on Achilles tendon, group 1 underwent aquatic activity
      for 8 weeks (five sessions per week), group 2 received intra-articular PRP (1
      ml), group 3 had aquatic activity together with injection PRP injection after an
      experimental tendon injury, group 4 did not receive any treatment after tendon
      injury and the control group with no tendon injuries. of 32 rats. After 8 weeks,
      the animals were sacrificed and the tendons were transferred in 10% formalin for
      histological evaluation. RESULTS: There was a significant increase in number of
      fibroblast and cellular density, and collagen deposition in group 3 comparing to
      other groups denoting to an effective healing in injured tendons. However, there
      was no significant difference among the studied groups based on their tendons
      diameter. CONCLUSION: Based on our findings on the number of fibroblast, cellular
      density, collagen deposition, and tendon diameter, it was shown that aquatic
      activity together with PRP injection was the therapeutic measure of choice
      enhance healing in tendon injuries that can open a window in treatment of damages
      to tendons.

PMID- 25606480
TI  - Nasal alar necrosis following hyaluronic Acid injection into nasolabial folds: a
      case report.
AB  - Injection of synthetic fillers for soft tissue augmentation is increasing over
      the last decade. One of the most common materials used is hyaluronic acid (HA)
      that is safe and temporary filler for soft tissue augmentation. We present a case
      of 54-year-old female who experienced vascular occlusion and nasal alar necrosis
      following HA injection to the nasolabial folds. She suffered from pain, necrosis,
      infection, and alar loss that finally required a reconstructive surgery for
      cosmetic appearance of the nose. The case highlights the importance of proper
      injection technique by an anesthesiologist, as well as the need for immediate
      recognition and treatment of vascular occlusion. 

PMID- 25606481
TI  - Successful propranolol treatment of a large size infantile hemangioma of the face
      causing recurrent bleeding and visual field disruption.
AB  - A 29 days old Pakistani female infant was presented to our outpatient department
      with two weeks history of a rapidly progressing large size facial hemangioma
      involving most of the right cheek and right eyelids. The infant was unable to
      open the right eye. There was also a small hemangioma on the right second toe.
      Additionally, three similar lesions were found on the right side of the palate
      and adjoining buccogingival surfaces. The parents were particularly concerned
      about the explosive progression of the lesions, recurrent bleeding episodes from
      ulcerated areas of the cheek lesion and complete occlusion of the right eye.
      Following four weeks therapy with propranolol in a dose of 2 mg/kg/day, the
      hemangiomas rapidly regressed, the bleeding episodes ceased and the infant
      started opening the eye. 

PMID- 25606482
TI  - Tips on writing and reviewing articles as a non-english speaking medical doctor.

PMID- 25606483
TI  - The clinical implications of poly implant prothese breast implants: an overview.
AB  - Mammary implants marketed by Poly Implant Prothese (PIP) were found to contain
      industrial grade silicone and this caused heightened anxiety and extensive
      publicity regarding their safety in humans. These implants were used in a large
      number of patients worldwide for augmentation or breast reconstruction. We
      reviewed articles identified by searches of Medline, PubMed, Embase, and Google
      Scholar databases up to May 2014 using the terms: "PIP", "Poly Implant Prothese",
      "breast implants" and "augmentation mammoplasty" "siloxanes" or "silicone". In
      addition the websites of regulating bodies in Europe, USA, and Australia were
      searched for reports related to PIP mammary implants. PIP mammary implants are
      more likely to rupture than other implants and can cause adverse effects in the
      short to the medium term related to the symptoms of rupture such as pain, lumps
      in the breast and axilla and anxiety. Based on peer-reviewed published studies we
      have calculated an overall rupture rate of 14.5% (383/2,635) for PIP implants.
      However, there is no evidence that PIP implant rupture causes long-term adverse
      health effects in humans so far. Silicone lymphadenopathy represents a foreign
      body reaction and should be treated conservatively. The long-term adverse effects
      usually arise from inappropriate extensive surgery, such as axillary lymph node
      dissection or extensive resection of breast tissue due to silicone leakage. 

PMID- 25606484
TI  - KCl Mediates K(+) Channel-Activated Mitogen-Activated Protein Kinases Signaling
      in Wound Healing.
AB  - BACKGROUND: Wound healing is an interaction of a complex signaling cascade of
      cellular events, including inflammation, proliferation, and maturation. K(+)
      channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway.
      Here, we investigated whether K(+) channel-activated MAPK signaling directs
      collagen synthesis and angiogenesis in wound healing. METHODS: The human skin
      fibroblast HS27 cell line was used to examine cell viability and collagen
      synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8)
      and western blotting. To investigate whether K(+) ion channels function upstream
      of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we
      examined alteration of MAPK expression after treatment with KCl (channel
      inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the
      effect of KCl on angiogenesis, angiogenesis-related proteins such as
      thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor
      (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were
      assayed by western blot. RESULTS: The viability of HS27 cells was not affected by
      25 mM KCl. Collagen synthesis increased dependent on time and concentration of
      KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal
      regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment
      cells and were inhibited by treatment of NS1619. TSP1 expression increased by
      100%, bFGF expression decreased by 40%, and there is no significant differences
      in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase
      inhibitors. CONCLUSIONS: Our results suggest that KCl may function as a
      therapeutic agent for wound healing in the skin through MAPK signaling mediated
      by the K(+) ion channel.

PMID- 25606485
TI  - Regulation of Transforming Growth Factor beta1, Platelet-Derived Growth Factor,
      and Basic Fibroblast Growth Factor by Silicone Gel Sheeting in Early-Stage
      Scarring.
AB  - BACKGROUND: Hypertrophic scars and keloids are associated with abnormal levels of
      growth factors. Silicone gel sheets are effective in treating and preventing
      hypertrophic scars and keloids. There has been no report on the change in growth
      factors in the scar tissue following the use of silicone gel sheeting for scar
      prevention. A prospective controlled trial was performed to evaluate whether
      growth factors are altered by the application of a silicone gel sheet on a fresh
      surgical scar. METHODS: Four of seven enrolled patients completed the study.
      Transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF),
      and basic fibroblast growth factor (bFGF) were investigated immunohistochemically
      in biopsies taken from five scars at 4 months following surgery. RESULTS: In both
      the epidermis and the dermis, the expression of TGF-beta1 (P=0.042 and P=0.042)
      and PDGF (P=0.043 and P=0.042) was significantly lower in the case of silicone
      gel sheet-treated scars than in the case of untreated scars. The expression of
      bFGF in the dermis was significantly higher in the case of silicone gel sheet
      treated scars than in the case of untreated scars (P=0.042), but in the
      epidermis, the expression of bFGF showed no significant difference between the
      groups (P=0.655). CONCLUSIONS: The levels of TGF-beta1, PDGF, and bFGF are
      altered by the silicone gel sheet treatment, which might be one of the mechanisms
      of action in scar prevention.

PMID- 25606486
TI  - Topical EMLA Cream as a Pretreatment for Facial Lacerations.
AB  - BACKGROUND: Topical anesthetics, such as eutectic mixture of local anesthetics
      (EMLA) cream, can be applied to reduce pain before minor procedure. This trial
      evaluated EMLA as pretreatment for facial lacerations and compared pain,
      discomfort and overall satisfaction. METHODS: This trial included consecutive
      emergency department patients >=16 years of age who presented with simple facial
      lacerations. At triage, lacerations were allotted to either the routine
      processing group or EMLA pretreatment group according to date of admission.
      Initially, the emergency department doctors inspected each laceration, which were
      dressed with saline-soaked gauze. In the pretreatment group, EMLA cream was
      applied during wound inspection. The plastic surgeon then completed primary
      closure following the local injection of an anesthetic. After the procedure, all
      patients were given a questionnaire assessing pain using the 10-point visual
      analog scale (VAS) ("no pain" to "worst pain"). All questionnaires were collected
      by the emergency department nurse before discharge. RESULTS: Fifty patients were
      included in the routine processing group, and fifty patients were included in the
      EMLA pretreatment group. Median age was 39.9 years, 66% were male, and the
      average laceration was 2.67 cm in length. The EMLA pretreatment group reported
      lower pain scores in comparison with the routine processing group (2.4 vs. 4.5 on
      VAS, P<0.05), and lower discomfort scores during the procedure (2.0 vs. 3.3,
      P=0.60). Overall satisfaction was significantly higher in the EMLA pretreatment
      group (7.8 vs. 6.1, P<0.05). CONCLUSIONS: Pretreating facial lacerations with
      EMLA topical cream aids patients by reducing pain and further enhancing overall
      satisfaction during laceration treatment.

PMID- 25606487
TI  - Analysis of patients with facial lacerations repaired in the emergency room of a
      provincial hospital.
AB  - BACKGROUND: Facial laceration is the most common injury encountered in the
      emergency room in the plastic surgery field, and optimal treatment is important.
      However, few authors have investigated this injury in all age groups or performed
      follow-up visit after repair. In the present study, the medical records of
      patients with lacerations in the facial area and underwent primary repair in an
      emergency room over a 2-year period were reviewed and analyzed. METHODS: Medical
      records of 3,234 patients with lacerations in facial area and underwent primary
      repair in an emergency room between March 2011 and February 2013 were reviewed
      and identified. RESULTS: All the 3,234 patients were evaluated, whose ratio of
      men to women was 2.65 to 1. The forehead was the most common region affected and
      a slip down was the most common mechanism of injury. In terms of monthly
      distribution, May had the highest percentage. 1,566 patients received follow-up
      managements, and 58 patients experienced complications. The average days of
      follow-up were 9.8. CONCLUSIONS: Proportion of male adolescents was significantly
      higher than in the other groups. Facial lacerations exhibit a 'T-shaped' facial
      distribution centered about the forehead. Careful management is necessary if a
      laceration involves or is located in the oral cavity. We were unable to long term
      follow-up most patients. Thus, it is necessary to encourage patients and give
      them proper education for follow-up in enough period.

PMID- 25606488
TI  - Medial and lateral canthal reconstruction with an orbicularis oculi myocutaneous
      island flap.
AB  - BACKGROUND: The eyelid and canthal areas are common locations for cutaneous
      tumors. The medial canthus includes, among many other apparatuses, the canthal
      tendon and lacrimal canaliculi, and its characteristic thin and supple skin is
      hard to mimic and restore using tissue from other regions. Accordingly,
      reconstruction of the canthal area can prove challenging for surgeons. Although
      various methods, such as skin grafts and local flaps from adjacent regions, have
      been utilized for reconstructive purposes, they present known disadvantages.
      However, we were able to successfully reconstruct both lateral and medial canthal
      area defects by using orbicularis oculi myocutaneous island flaps. METHODS: Our
      study included seven patients who underwent medial or lateral canthal region
      reconstruction, using orbicularis oculi myocutaneous island flaps, between 2011
      and 2014, following either cutaneous tumor excision or traumatic avulsion injury.
      RESULTS: Five patients had basal cell carcinoma, one had squamous cell carcinoma
      of the eyelid, and one had sustained a traumatic avulsion injury of the eyelid
      and canthal area. Entire flap loss was not observed in any patient, but one-a
      heavy smoker-showed partial flap loss, which healed with secondary intention and
      yielded acceptable results. Donor site morbidity was not observed, and all
      patients were satisfied with their surgical outcomes. CONCLUSIONS: The canthal
      regions can be successfully reconstructed with orbicularis oculi myocutaneous
      island flaps. These flaps offer several key advantages, including similarity in
      texture, color, and thickness to the recipient site and a negligible incidence of
      donor site morbidity.

PMID- 25606489
TI  - Cognitive investigation study of patients admitted for cosmetic surgery:
      information, expectations, and consent for treatment.
AB  - BACKGROUND: In all branches of medicine, it is the surgeon's responsibility to
      provide the patient with accurate information before surgery. This is especially
      important in cosmetic surgery because the surgeon must focus on the aesthetic
      results desired by the patient. METHODS: An experimental protocol was developed
      based on an original questionnaire given to 72 patients. The nature of the
      responses, the patients' motivation and expectations, the degree of patient
      awareness regarding the planned operation, and the patients' perceptions of the
      purpose of the required consent for cosmetic surgery were all analyzed using
      Fisher's exact test. RESULTS: Candidates for abdominal wall surgery had
      significantly more preoperative psychological problems than their counterparts
      did (P=0.035). A significantly different percentage of patients under 40 years of
      age compared to those over 40 years of age searched for additional sources of
      information prior to the operation (P=0.046). Only 30% of patients with a lower
      educational background stated that the preoperative information had been
      adequate, whereas 92% of subjects with secondary schooling or a postsecondary
      degree felt that the information was sufficient (P=0.001). A statistically
      significant difference was also present between patients according to their
      educational background regarding expected improvements in their quality of life
      postoperatively (P=0.008). CONCLUSIONS: This study suggests that patients require
      more attention in presurgical consultations and that clear communication should
      be prioritized to ensure that the surgeon understands the patient's expectations.

PMID- 25606490
TI  - A Pilot Study of Skin Resurfacing Using the 2,790-nm Erbium:YSGG Laser System.
AB  - BACKGROUND: The erbium:yttrium scandium gallium garnet (Er:YSGG) laser differs
      from other laser techniques by having a faster and higher cure rate. Since the
      Er:YSGG laser causes an appropriate proportion of ablation and coagulation, it
      has advantages over the conventional carbon dioxide (CO2) laser and the erbium
      doped yttrium aluminum garnet (Er:YAG) laser, including heating tendencies and
      explosive vaporization. This research was conducted to explore the effects and
      safety of the Er:YSGG laser. METHODS: Twenty patients participated in the pilot
      study of a resurfacing system using a 2,790-nm Er:YSGG laser. All patients
      received facial treatment by the 2,790-nm Er:YSGG laser system (Cutera) twice
      with a 4-week interval. Wrinkle reduction, reduction in pigment inhomogeneity,
      and improvement in tone and texture were measured. RESULTS: Study subjects
      included 15 women and five men. Re-epithelization occurred in all subjects 3 to 4
      days after treatment, and wrinkle reduction, reduction in pigment inhomogeneity,
      and improvement in tone and texture within 6 months of treatment. CONCLUSIONS:
      The 2,790-nm YSGG laser technique had fewer complications and was effective in
      the improvement of scars, pores, wrinkles, and skin tone and color with one or
      two treatments. We expect this method to be effective for people with acne scars,
      pore scars, deep wrinkles, and uneven skin texture and color.

PMID- 25606492
TI  - Treatment of the Mycobacterium chelonae Infection after Fat Injection.
AB  - For recent years, use of autologous fat injection has increased significantly in
      facial contouring surgery. Along with such increase in use, complications like
      atypical mycoplasma infection have been also on the increasing trend. The authors
      report two cases of Mycobacterium chelonae infection that occurred after
      autologous fat injection. Patients were treated as infection that resistant to
      common antibiotics and results were negative to routine culture and Gram
      staining. Acid-fast bacillus stain, polymerase chain reaction (PCR) test and
      mycobacterial cultures were conducted for diagnosis under suspicion of atypical
      mycoplasma infection. Then, combination antibiotics therapy, surgical treatment,
      and steroid injection were performed for treatment. Both patients were diagnosed
      with Mycobacterium chelonae in PCR test. They were positive to mycobacterial
      cultures. Combination antibiotics therapy was repeated to improvement of symptom.
      However, they could not be free from side effects such as deformation in facial
      contour, scar and pigmentation even after full recovery. When chronic wound
      infections after autologous fat injection, we must suspect atypical or
      mycobacterial infection and conduct examinations for a early diagnosis and proper
      antibiotic therapy that is effective to the nontuberculous mycobacteria. 

PMID- 25606491
TI  - Negative pressure wound therapy of chronically infected wounds using 1% acetic
      Acid irrigation.
AB  - BACKGROUND: Negative-pressure wound therapy (NPWT) induces angiogenesis and
      collagen synthesis to promote tissue healing. Although acetic acid soaks
      normalize alkali wound conditions to raise tissue oxygen saturation and
      deconstruct the biofilms of chronic wounds, frequent dressing changes are
      required. METHODS: Combined use of NPWT and acetic acid irrigation was assessed
      in the treatment of chronic wounds, instilling acetic acid solution (1%) beneath
      polyurethane membranes twice daily for three weeks under continuous pressure (125
      mm Hg). Clinical photographs, pH levels, cultures, and debrided fragments of
      wounds were obtained pre- and posttreatment. Tissue immunostaining (CD31, Ki-67,
      and CD45) and reverse transcription-polymerase chain reaction (vascular
      endothelial growth factor [VEGF], vascular endothelial growth factor receptor
      [VEGFR]; procollagen; hypoxia-inducible factor 1 alpha [HIF-1-alpha]; matrix
      metalloproteinase [MMP]-1,-3,-9; and tissue inhibitor of metalloproteinase
      [TIMP]) were also performed. RESULTS: Wound sizes tended to diminish with the
      combined therapy, accompanied by drops in wound pH (weakly acidic or neutral) and
      less evidence of infection. CD31 and Ki-67 immunostaining increased (P<0.05) post
      treatment, as did the levels of VEGFR, procollagen, and MMP-1 (P<0.05), whereas
      the VEGF, HIF-1-alpha, and MMP-9/TIMP levels declined (P<0.05). CONCLUSIONS: By
      combining acetic acid irrigation with negative-pressure dressings, both the pH
      and the size of chronic wounds can be reduced and infections be controlled. This
      approach may enhance angiogenesis and collagen synthesis in wounds, restoring the
      extracellular matrix.

PMID- 25606493
TI  - The axillary approach to raising the latissimus dorsi free flap for facial re
      animation: a descriptive surgical technique.
AB  - The latissimus dorsi flap is popular due to the versatile nature of its
      applications. When used as a pedicled flap it provides a robust solution when
      soft tissue coverage is required following breast, thoracic and head and neck
      surgery. Its utilization as a free flap is extensive due to the muscle's size,
      constant anatomy, large caliber of the pedicle and the fact it can be used for
      functional muscle transfers. In facial palsy it provides the surgeon with a long
      neurovascular pedicle that is invaluable in situations where commonly used facial
      vessels are not available, in congenital cases or where previous free functional
      muscle transfers have been attempted, or patients where a one-stage procedure is
      indicated and a long nerve is required to reach the contra-lateral side. Although
      some facial palsy surgeons use the trans-axillary approach, an operative guide of
      raising the flap by this method has not been provided. A clear guide of raising
      the flap with the patient in the supine position is described in detail and
      offers the benefits of reducing the risk of potential brachial plexus injury and
      allows two surgical teams to work synchronously to reduce operative time. 

PMID- 25606494
TI  - Preoperative identification of a perforator using computed tomography angiography
      and metal clip marking in perforator flap reconstruction.
AB  - In perforator flap reconstruction, vascular mapping using preoperative computed
      tomography (CT) angiography is widely used to confirm the existence and location
      of an appropriate perforator. This study proposes a rapid, accurate, and
      convenient method for marking the perforator location on the skin surface. For 12
      patients who underwent perforator flap reconstruction between November 2011 and
      November 2013, metal clips were fixed on the skin surface at the anticipated
      perforator locations, which were decided using a handheld Doppler. CT angiography
      was used to compare the location between the metal clip and the actual
      perforator. The metal clip was moved and repositioned, if needed, on the basis of
      the CT images. The locations of the appropriate perforator and the metal clip,
      which were observed during the surgery, were then compared. In CT angiography,
      the mean distance between the metal clip and the perforator was 3+/-3.9 mm, and
      the mean distance that was measured during surgery was 0.8+/-0.8 mm. In
      conclusion, we report a simple, rapid, and precise technique to indicate the
      accurate location of the appropriate perforator on the skin surface. 

PMID- 25606495
TI  - Transient hair loss after finger replantation.

PMID- 25606496
TI  - An unexpected etiology of a subcutaneous mass: hydatid cyst.

PMID- 25606497
TI  - Experience of adult-onset velopharyngeal insufficiency after tuberculosis of the
      soft palate.

PMID- 25606498
TI  - Clinical experience of morel-lavallee syndrome.

PMID- 25606499
TI  - Extravasation of a percutaneous femoral hepatic infusion device.

PMID- 25606500
TI  - Gemella morbillorum Infection after Acupuncture Therapy.

PMID- 25606501
TI  - Leiomyoma on nasal dorsum.

PMID- 25606502
TI  - The Rare Presentation of Extraskeletal Ewing's Sarcoma on the Forehead.

PMID- 25606504
TI  - Editorial.

PMID- 25606503
TI  - A rare case of peripheral osteoma of the zygoma.

PMID- 25606505
TI  - Posterior cruciate ligament-retaining and posterior-stabilized total knee
      arthroplasty: differences in surgical technique.
AB  - The debate over the relative merits of substituting or retaining the posterior
      cruciate ligament in total knee arthroplasty is still ongoing. This article
      discusses the differences between the two procedures, considering the
      biomechanics and the surgical techniques involved. 

PMID- 25606506
TI  - Patellar malalignment treatment in total knee arthroplasty.
AB  - The patella, with or without resurfacing, plays a fundamental role in the success
      of a total knee arthroplasty (TKA). Patellofemoral joint complications are due to
      problems related to the patient, to the surgical technique, or to the design of
      the components. Patellar tracking is influenced by several factors: a severe
      preoperative valgus, the presence of pre-existing patellofemoral dysplasia, the
      design of the femoral component, the surgical approach, the Q angle, the
      mechanical alignment of the limb, the tightness of the lateral retinaculum, the
      positioning of the patellar component in the proximal-distal and medial-lateral
      directions, the patella height, the patella (native or resurfaced) thickness, the
      size of the femoral and the tibial components, and the alignment and rotation of
      the components. Several factors are crucial to prevent patellar maltracking in
      TKA: the use of an anatomical femoral component, a meticulous surgical technique,
      careful dynamic intraoperative assessment of patellar tracking, and, if
      necessary, the achievement of an adequate lateral release. 

PMID- 25606507
TI  - ACL Reconstruction: Choosing the Graft.
AB  - Rupture of the anterior cruciate ligament is one of the most common ligament
      injuries in sports traumatology. The need for surgical anterior cruciate ligament
      reconstruction is justified by its anatomical characteristics. Key considerations
      when choosing a graft include the potential for bone integration and the risk of
      failure. Bone sclerosis around the tunnel affects the integration of the graft.
      For this reason, one aspect upon which orthopedic surgeons should focus is the
      biology of the bone-graft interface. Although the BPTB graft is still used,
      hamstrings and synthetic grafts have become increasingly widespread and popular
      over the years. An allograft certainly requires more long-term follow-up to
      validate its use in response to functional, clinical and biological requirements.

PMID- 25606508
TI  - Pre-operative planning in anterior cruciate ligament reconstruction revision
      surgery.
AB  - Primary reconstructions of the anterior cruciate ligament are common and
      increasing in number, a trend inevitably paralleled by an increase in the number
      of revision procedures. Failure of primary ACL reconstruction can appear as
      objective residual laxity, subjective instability, severe and persistent
      postoperative stiffness and/or pain, or infection. Revision surgery is a complex
      procedure, in which the expected clinical outcome is inferior to that which can
      be expected from primary reconstruction, and patients have a 5.4% risk of
      undergoing a second revision after five years. This type of procedure demands
      correct and exhaustive preoperative planning so as ensure optimal treatment of
      accompanying lesions and of any complications arising during surgery. It is
      important to know, in detail, the patient's clinical history (when the primary
      surgery was performed and the technique used, the cause of the recurrence, the
      degree of functional recovery, etc.), to perform a thorough clinical examination
      (to evaluate alignment, gait cycle, skin color, the trophic condition of the
      muscles, joint laxity), and to have available the results of a detailed and
      specific imaging study and also of blood tests, in order to exclude the presence
      of an infection. 

PMID- 25606510
TI  - Editorial.

PMID- 25606509
TI  - Patellofemoral instability: surgical treatment of soft tissues.
AB  - Instability of the patella is a relatively frequent occurrence in adolescents.
      Its pathogenesis, which is multi-factorial, is still much debated. Stability of
      the patella is guaranteed by a delicate balance of a series of factors (osteo
      cartilaginous, ligamentous and muscular), and it is not surprising that
      alteration of one or more of these can lead to pathological conditions that can
      range from simple anterior pain associated with a hypermobile patella to
      recurrent dislocation. The aim of surgical treatment is to correct these
      anatomical abnormalities. Surgical procedures on the soft tissues comprise
      reefing, realignment and reconstruction of the medial stabilizing structures, and
      release of the lateral structures. These procedures, although having precise
      indications, provide the surgeon with the instruments necessary to deal with
      almost all these anatomo-pathological conditions. Furthermore, preserving the
      osteo-cartilaginous components results in less morbidity than is associated with
      traditional surgical procedures, such as trochleoplasty and transposition of the
      anterior tibial tuberosity. 

PMID- 25606511
TI  - Patellofemoral instability: classification and imaging.
AB  - Patellofemoral disorders must be approached through an appropriate process of
      diagnostic framing, performed using language that is, as far as possible,
      unequivocal and a validated and organic classification system. At present, the
      classification proposed by the Lyonnaise school, which fulfills these
      requirements, is the most complete. This classification divides patellofemoral
      disorders into three groups: objective patellar instability, potential patellar
      instability and painful patella syndrome. It also identifies three principal
      factors of instability: trochlear dysplasia, abnormal patellar height and
      pathological tibial tubercle-trochlear groove (TT-TG) distance. Imaging is
      crucial for correct classification and for identifying and measuring the
      principal factors of instability. Up to now, the emphasis has been placed on the
      contribution made by traditional diagnostic radiology and computed tomography. In
      recent years, however, growing attention has been paid to the use of magnetic
      resonance imaging in the assessment of the patellofemoral joint and in the study
      of factors of instability, even though there is still a need for validation of
      this approach before it can be routinely used in preoperative planning. 

PMID- 25606513
TI  - Extensor mechanism realignment procedures in the treatment of patellofemoral
      instability.
AB  - Patellar instability is one of the most common conditions treated in the field of
      orthopedics. A diagnosis based on clinical and instrumental tests allows proper
      treatment planning. The techniques at the disposal of the surgeon - arthroscopic,
      arthroscopically-assisted and open - are numerous, and extensor mechanism
      realignment procedures are among the ones most frequently used. The choice of the
      most appropriate technique must be made case by case, considering the
      peculiarities of the individual patient. 

PMID- 25606512
TI  - Patellofemoral anatomy and biomechanics: current concepts.
AB  - The patellofemoral joint, due to its particular bone anatomy and the numerous
      capsuloligamentous structures and muscles that act dynamically on the patella, is
      considered one of the most complex joints in the human body from the
      biomechanical point of view. The medial patellofemoral ligament (MPFL) has been
      demonstrated to contribute 60% of the force that opposes lateral displacement of
      the patella, and MPFL injury results in an approximately 50% reduction in the
      force needed to dislocate the patella laterally with the knee extended. For this
      reason, recent years have seen a growing interest in the study of this important
      anatomical structure, whose aponeurotic nature has thus been demonstrated. The
      MPFL acts as a restraint during motion, playing an active role under conditions
      of laterally applied stress, but an only marginal role during natural knee
      flexion. However, it remains extremely difficult to clearly define the anatomy of
      the MPFL and its relationships with other anatomical structures. 

PMID- 25606514
TI  - Patellofemoral malalignment and chondral damage: current concepts.
AB  - Patellofemoral disorders can be classified according to specific criteria, and
      the most well-known classification systems are Insall's classification and
      Merchant's classification. In this work, after completion of an in-depth
      literature review, we will analyze the most frequent patellofemoral pathologies
      with the aim of determining the correct clinical-diagnostic-therapeutic course.
      Pathologies of greater clinical frequency will be examined in detail to provide
      the most relevant didactic scope. We will therefore address the following
      pathologies: excessive lateral patellar compression syndrome; patellar
      dislocations and subluxations; patellar chondromalacia; and patellofemoral
      osteoarthritis. 

PMID- 25606516
TI  - Unicompartmental knee replacement: a historical overview.
AB  - There is currently a growing demand for unicompartmental knee replacement (UKR)
      to treat degenerative osteoarthritis or osteonecrosis of a single compartment of
      the knee. This procedure has evolved significantly over the past three decades
      and we here present a brief review of the literature on this topic. This
      historical overview traces the hypotheses that have led to the modern state of
      the art in minimally invasive UKR surgery and to the revival of the concept of
      interpositional hemiarthroplasty. 

PMID- 25606515
TI  - Surgical approaches in total knee arthroplasty.
AB  - Total knee replacement surgery begins with correct planning of both the incision
      and the exposure of the joint. Indeed, these are factors that are just as crucial
      to an optimal outcome as choosing the right implant, positioning the components,
      and balancing the ligaments. While it is true that the standard incision and
      arthrotomy (with which we are most familiar) will, in most primary implant cases,
      provide adequate joint exposure, it is also true that cases characterized by
      certain conditions, such as previous cutaneous incisions, a stiff knee or patella
      baja, present specific skin and exposure problems that need to be recognized,
      planned for and overcome. 

PMID- 25606517
TI  - Editorial.

PMID- 25606518
TI  - One-step bone marrow-derived cell transplantation in talarosteochondral lesions:
      mid-term results.
AB  - PURPOSE: to verify the capability of scaffold-supported bone marrow-derived cells
      to be used in the repair of osteochondral lesions of the talus. METHODS: using a
      device to concentrate bone marrow-derived cells, a scaffold (collagen powder or
      hyaluronic acid membrane) for cell support and platelet gel, a one-step
      arthroscopic technique was developed for cartilage repair. In a prospective
      clinical study, we investigated the ability of this technique to repair talar
      osteochondral lesions in 64 patients. The mean follow-up was 53 months. Clinical
      results were evaluated using the American Orthopaedic Foot and Ankle Society
      (AOFAS) scale score. We also considered the influence of scaffold type, lesion
      area, previous surgery, and lesion depth. RESULTS: the mean preoperative AOFAS
      scale score was 65.2 +/- 13.9. The clinical results peaked at 24 months, before
      declining gradually to settle at a score of around 80 at the maximum follow-up of
      72 months. CONCLUSIONS: the use of bone marrow-derived cells supported by
      scaffolds to repair osteochondral lesions of the talus resulted in significant
      clinical improvement, which was maintained over time. LEVEL OF EVIDENCE: level
      IV, therapeutic case series.

PMID- 25606519
TI  - The role of arthroscopic capsulo-labral repair in unidirectional post-traumatic
      shoulder instability in adolescent athletes participating in overhead or contact
      sports.
AB  - PURPOSE: this study was performed to identify the role of arthroscopic capsulo
      labral repair (ACR) in unidirectional post-traumatic shoulder instability in
      adolescent athletes participating in overhead or contact sports. METHODS: sixty
      five adolescent patients (aged 13 to 18 years) with post-traumatic shoulder
      instability submitted to arthroscopic surgery were selected from our database.
      The mean follow-up duration was 63 months. Shoulder range of motion and
      functional outcomes were evaluated preoperatively and postoperatively using the
      Single Assessment Numeric Evaluation (SANE), Rowe, and American Shoulder and
      Elbow Surgeons (ASES) scores. In addition, details in the database on the type of
      sport practiced, time until surgery, and number of dislocations were analyzed to
      look for possible correlations with the recurrence rate. RESULTS: at the final
      follow-up, the mean SANE score was 87.23% (range: 30% to 100%) (preoperative mean
      score: 46.15% [range, 20% to 50%]); the mean Rowe score was 85 (range: 30 to 100)
      (preoperative mean score: 35.9 [range: 30 to 50]); and the mean ASES score was
      84.12 (range: 30 to 100) (preoperative mean score: 36.92 [range: 30 to 48]). Mean
      forward flexion and external rotation with the arm at 90 degrees  abduction did
      not show changes compared with preoperative values; 81.5% of the patients
      returned to their pre-injury level of sports activities, and the failure rate was
      21.5%. The recurrence rate was not related to the postoperative scores (p = 0.556
      for SANE, p = 0.753 for Rowe, and p = 0.478 for ASES), number of preoperative
      episodes of instability (p = 0.59), or time that elapsed between the first
      instability episode and the surgery (p = 0.43). A statistically significant
      association (p = 0.0021) was found between recurrence and the type of sport
      practiced. CONCLUSIONS: ACR is a reasonable surgical option in an adolescent
      population participating in sports. It has a role in restoring shoulder stability
      with very low morbidity; however, the failure rate is higher than in the adult
      population and both the young patients and their relatives must be properly
      informed about the expected outcome of the procedure. LEVEL OF EVIDENCE: level
      IV, therapeutic case series.

PMID- 25606520
TI  - Leukocyte-poor PRP application for the treatment of knee osteoarthritis.
AB  - PURPOSE: the aim of this study was to describe the clinical results obtained
      after intra-articular injection of a leukocyte-poor platelet-rich plasma (PRP)
      preparation for the treatment of knee osteoarthritis (OA). METHODS: forty-five
      patients (mean age: 59 years, mean BMI: 27) were included and treated with a
      cycle of three weekly injections of autologous conditioned plasma. Six patients
      were affected by bilateral symptomatic OA, therefore 51 knees in total were
      treated. The patients were divided into two groups: those affected by
      early/moderate OA and those affected by severe OA. The patients were submitted to
      baseline evaluation and evaluation after a mean follow-up of 14.5 months (range:
      6-24 months), performed using the following outcome measures: IKDC-subjective, EQ
      VAS, Tegner, and KOOS scores. Adverse events and patient satisfaction were also
      recorded. The results in the two groups of patients ("early/moderate" vs "severe
      OA") were analyzed separately. RESULTS: the overall clinical outcome was positive
      and the treatment proved to be safe. In the "early/moderate OA" group, the IKDC
      subjective score increased from 36.4 at the baseline evaluation to 57.3 at the
      follow-up (p<0.0005) and a similar trend was shown by the EQ-VAS, Tegner, and
      KOOS scores. Although an improvement was also recorded in the "severe OA" group,
      the clinical outcome of the patients in this group was significantly poorer and
      they reported less benefit. In the "early/moderate OA" group, BMI and longer
      symptom duration before treatment were found to be correlated with clinical
      outcome. CONCLUSIONS: PRP injections are capable of reducing pain and improving
      knee functional status at short-term follow-up. The patients with a lower degree
      of joint degeneration were the best responders, whereas in severe osteoarthritic
      knees this biological treatment, used as a "salvage procedure", produced a less
      favorable outcome. LEVEL OF EVIDENCE: level IV; therapeutic case series.

PMID- 25606521
TI  - Cemented versus cementless fixation in total knee arthroplasty.
AB  - The question of whether to use cemented or cement-less fixation for a total knee
      arthroplasty (TKA) is still debated. Discouraging preliminary results of cement
      less TKAs have determined the worldwide use of cemented implants. However, with
      the development of biotechnologies and new biomaterials with high osteoconductive
      properties, biological fixation is now becoming an attractive option for
      improving the longevity of TKAs, especially in young patients. There is no
      evidence in the current literature to support the use of one method of fixation.
      The extensive clinical experience with cemented implants gathered over the years
      justifies their widespread use. New randomized clinical trials are necessary to
      compare cementless fixation based on the new ingrowth surfaces with standard
      cemented implants. 

PMID- 25606522
TI  - Femoral tunnel in revision anterior cruciate ligament reconstruction.
AB  - The failure rate after anterior cruciate ligament (ACL) reconstruction performed
      by expert surgeons is estimated to be in the range of 10-15%, and only 60% of
      patients undergoing this surgery are able to resume sporting activities
      comparable to those they engaged in prior to the traumatic incident. Incorrect
      femoral tunnel placement is one of the main causes of failed ACL reconstruction
      and this must be remembered when undertaking revision surgery. There are various
      possible errors that can be committed and, to plan revision surgery correctly, it
      is fundamental to study the position of the existing femoral tunnel(s) both on
      classic anteroposterior and lateral plain radiographs and on computed tomography
      scans with frontal, sagittal, and coronal sections, and also using three
      dimensional reconstruction. In-depth anatomical knowledge and familiarity with
      the various possible surgical techniques are also mandatory for a successful
      surgical outcome. 

PMID- 25606523
TI  - The biomaterialist's task: scaffold biomaterials and fabrication technologies.
AB  - This paper focuses on tissue engineering (TE) from the biomaterialist's point of
      view. With the aim of answering some simple but key questions about TE, the
      related literature is here reviewed. In order to obtain an engineered tissue the
      following steps are mandatory: (a) cell selection, (b) identification of the
      ideal three-dimensional scaffold for cell seeding and proliferation, (c) choice
      of the most suitable type of cell culture. Whereas the biotechnologist working in
      the TE field is responsible for optimizing the cell seeding and culture, the
      biomaterialist has the challenging task of optimizing the three-dimensional cell
      support, or scaffold. Therefore, in the present paper, scaffold properties,
      biomaterials and fabrication technologies are analyzed in depth and reviewed on
      the basis of the current literature. Finally, mention is also made of the most
      recently emerging and innovative technologies relating to scaffolds for TE
      applications. 

PMID- 25606525
TI  - Editorial.

PMID- 25606526
TI  - Bipolar fresh osteochondral allograft of the shoulder.
AB  - PURPOSE: to describe an original technique and preliminary results of bipolar
      fresh osteochondral allograft implantation for the treatment of end-stage
      glenohumeral osteoarthritis. METHODS: three patients underwent bipolar fresh
      osteochondral allograft implantation to the shoulder. Clinical and radiographical
      evaluations were carried out periodically through to final follow-up. RESULTS:
      constant Score increased from 38.3 +/- 2.9 pre-operatively to 78.7 +/- 16.2 at 12
      months, 72.3 +/-15.3 at 24 months, and 59.3 +/- 22.0 at 34 months. Arthritis and
      partial reabsorption of the implanted surfaces were evident radiographically.
      CONCLUSIONS: the clinical results obtained in these patients seem to support the
      applicability of bipolar fresh osteochondral allograft implantation in the
      shoulder in subjects with severe post-traumatic arthritis and intact rotator
      cuff. The development of arthritis of the implanted surfaces, while not impacting
      the clinical result, is a cause of concern. LEVEL OF EVIDENCE: level IV,
      therapeutic case series.

PMID- 25606524
TI  - Surgical treatment of trapeziometacarpal joint osteoarthritis.
AB  - Trapeziometacarpal joint osteoarthritis is a common cause of radial-sided wrist
      pain that prevalently affects women. It is diagnosed on the basis of a thorough
      history, physical examination, and radiographic evaluation. While radiographs are
      used to determine the stage of disease, treatment is dependent on the severity of
      the symptoms. Non-surgical treatment frequently consists of activity
      modification, non-steroidal anti-inflammatory drugs, splinting and corticosteroid
      injections. After failure of conservative treatment, various surgical options
      exist depending on the stage of the disease. These options range from ligament
      reconstruction or osteotomy, for early painful laxity, to trapeziectomy,
      arthrodesis and arthroplasty for more severe osteoarthritis. This article reviews
      the literature supporting the various surgical treatment options and analyzes the
      surgical techniques most frequently used in the different disease stages. 

PMID- 25606527
TI  - Rotational alignment of the tibial component in total knee arthroplasty: the
      anterior tibial cortex is a reliable landmark.
AB  - PURPOSE: to compare the anterior tibial surface curvature, the Akagi's line and
      the medial third of the tibial tubercle in order to assess which is the most
      reliable landmark for correct tibial component rotational positioning in total
      knee arthroplasty. METHODS: three independent investigators reviewed 124 knee MRI
      scans. The most suitable tibial baseplate tracing for the Nexgen Total Knee
      System (Zimmer, Warsaw, USA) was superimposed on the scan matching the anterior
      tibial cortex with the anterior aspect of the baseplate. The rotation of the
      tibial baseplate tracing was calculated with respect to the transepicondylar axis
      (TEA), the medial third of the tibial tubercle line, Akagi's line and the femoral
      posterior condylar axis (PCA). Customized software was created and used for
      analysis of the MRI datasets. The reliability of each measurement was then
      calculated by using the intraclass correlation coefficient for interobserver
      agreement. RESULTS: observer agreement on the position of the Akagi's line was
      within 3 degrees  in 64% of the cases and within 5 degrees  in 85% of the cases.
      Agreement on the position of the medial third of the tibial tubercle was within 3
      degrees  in 29% of the cases and within 5 degrees  in 70% of the cases. Agreement
      on the localization of the anterior tibial surface curvature was within 3 degrees
      in 89% of the cases and within 5 degrees  in 99% of the cases. Component
      alignment along the anterior cortex guaranteed full matching +/- 3 degrees  with
      the epicondylar axis in 75% of the knees. CONCLUSIONS: the anterior tibial
      surface curvature was found to be a more reliable and more easily identifiable
      landmark for correct tibial component alignment than either Akagi's line or the
      medial third of the tibialtubercle. LEVEL OF EVIDENCE: level III, retrospective
      cohort study.

PMID- 25606528
TI  - Polyurethane scaffold for the treatment of partial meniscal tears. Clinical
      results with a minimum two-year follow-up.
AB  - PURPOSE: to evaluate the safety and effectiveness of the polyurethane meniscal
      scaffold through clinical examination, MRI and arthroscopic second look, over a
      minimum two-year follow-up. METHODS: between 2009 and 2011, 19 patients underwent
      meniscal scaffold implantation in our department (medial meniscus in 16 cases
      lateral meniscus in two cases, and bilateral in one case). All the patients were
      clinically evaluated preoperatively, and at 6, 12, and 24 months after surgery
      using Lysholm score, Tegner score, and VAS. Ten patients were studied with MRI,
      and nine patients were evaluated arthroscopically. RESULTS: no adverse reactions
      to the implant were observed. The clinical scores showed a significant
      improvement at 6 months and increased progressively over time. On MRI studies,
      the implants showed a clear hyperintense signal, sometimes irregular, and the
      chondral surface was preserved in all cases. At arthroscopic second look in the
      first months after surgery, the scaffold size was unchanged and the scaffold
      appeared light yellowish in color and well integrated into the surrounding
      tissues. At arthroscopic second look at 12 and 24 months the scaffold was found
      to have an irregular morphology and to be slightly reduced in size. CONCLUSIONS:
      polyurethane meniscal scaffold is a good alternative to a collagen scaffold, but
      a longer follow-up is needed to evaluate the scaffold degradation and chondral
      coverage. LEVEL OF EVIDENCE: level IV, therapeutic case series.

PMID- 25606529
TI  - The treatment of chondral lesions of the knee with the microfracture technique
      and platelet-rich plasma.
AB  - PURPOSE: to assess the efficacy of associating the microfracture technique with
      platelet-rich plasma (PRP) injections in the treatment of chondral lesions to
      promote acceleration and optimization of the healing process compared with the
      traditional microfracture approach. METHODS: from September 2011 to August 2012,
      20 patients (9 males and 11 females, aged 30-55 years) were treated. All
      presented with chondral lesions of the medial femoral condyle of the knee and a
      pain duration ranging from 8 to 12 months. The patients were randomized into two
      groups (A and B). Group A was treated with the microfracture technique and a
      total of three intra-articular injections of PRP. Group B was treated with
      microfractures alone. Clinical follow-up was performed at 3, 6 and 12 months
      after treatment. Clinical function was assessed on the basis of the International
      Knee Documentation Committee (IKDC) score. Pain was evaluated using a visual
      analogue scale (VAS). RESULTS: the patients in group A had a mean baseline IKDC
      score of 31.2, which rose to 84.2 at 12 months. The IKDC scores in group B were
      at 30.1 at baseline and 81 at 12 months. CONCLUSIONS: the results of our study
      suggest that functional recovery and resolution of pain are obtained more quickly
      in PRP-treated patients. We also observed a better functional outcome in the
      patients treated with the combination of PRP and microfractures, even at 12
      months, although the difference was not statistically significant. LEVEL OF
      EVIDENCE: level II, randomized clinical study.

PMID- 25606531
TI  - The effects of growth factors on skeletal muscle lesions.
AB  - Skeletal muscle injuries are common causes of severe long-term pain and physical
      disability, accounting for up to 55% of all sports injuries. The phases of the
      healing process after direct or indirect muscle injury are complex but clearly
      defined processes comprising well-coordinated steps: degeneration, inflammation,
      regeneration, and fibrosis. Despite this frequent occurrence and the presence of
      a body of data on the pathophysiology of muscle injuries, none of the treatment
      strategies adopted to date have been shown to be really effective in strictly
      controlled trials. Most current muscle injury treatments are based on limited
      experimental and clinical data and/or were only empirically tested. Platelet-rich
      plasma (PRP) is a promising alternative approach based on the ability of
      autologous growth factors (GFs) to accelerate tissue healing, improve muscular
      regeneration, increase neovascularization and reduce fibrosis, allowing rapid
      recovery after muscle lesions. Thus, further experimental studies that include
      the quantification of specific GFs released by PRP, as well as additional data on
      angiogenesis, myogenesis and functional recovery are needed to ultimately
      validate the hypothesis of PRP efficacy in the treatment of muscle lesions and
      open the way for its wide clinical application. 

PMID- 25606530
TI  - Generalized joint laxity and multidirectional instability of the shoulder.
AB  - Generalized joint laxity and shoulder instability are common conditions that
      exhibit a wide spectrum of different clinical forms and may coexist in the same
      patient. Generalized joint laxity can be congenital or acquired. It is
      fundamental to distinguish laxity from instability. Laxity is a physiological
      condition that may predispose to the development of shoulder instability. A high
      prevalence of generalized joint laxity has been identified in patients with
      multidirectional instability of the shoulder. Multidirectional instability is
      defined as symptomatic instability in two or more directions. The diagnosis and
      treatment of this condition are still challenging because of complexities in its
      classification and etiology. These complexities are compounded when
      multidirectional instability and laxity exist in the same patient. With an
      improved understanding of the clinical symptoms and physical examination
      findings, a successful strategy for conservative and/or surgical treatments can
      be developed. Conservative treatment is the first-line option. If it fails,
      different surgical options are available. Historically, open capsular shift has
      been considered the gold standard in the surgical management of these patients.
      Nowadays, advanced arthroscopic techniques offer several advantages over
      traditional open approaches and have shown similar outcomes. The correct approach
      to the management of failed stabilization procedures has not been yet defined. 

PMID- 25606532
TI  - Lamberto Perugia Lecture: The intuition and contribution of Lamberto Perugia and
      his fellows to anterior cruciate ligament reconstruction: Lecture given to the
      1(st) European Workshop on Ligaments and Tendons Arezzo October 19(th), 2013.

PMID- 25606534
TI  - Looking ahead and looking back: happy birthday joints!

PMID- 25606533
TI  - Recurrent anterior shoulder dislocation with glenoid bone loss and concurrent
      irreparable rotator cuff tear in a young patient: case report.
AB  - Full-thickness rotator cuff tear associated with gleno-humeral anterior
      dislocation is a rare injury in patients younger than 40 years of age. We here
      report a case of recurrent anterior shoulder dislocation with glenoid bone loss
      and concurrent irreparable rotator cuff tear in a young patient. This is, to the
      best of our knowledge, the first such case reported in the literature. We also
      discuss the type of surgical treatment adopted and the measures that can be
      undertaken to address both instability and massive rotator cuff tear. 

PMID- 25606535
TI  - Reconstruction of the coracoclavicular and acromioclavicular ligaments with
      semitendinosus tendon graft: a pilot study.
AB  - PURPOSE: this study was conducted to assess the safety and efficacy of a new
      surgical technique for anatomical reconstruction of the coracoclavicular (CC) and
      acromioclavicular (AC) ligaments using one single-strand semitendinosus tendon
      graft. METHODS: eighteen patients affected by chronic type III-V AC joint
      dislocations were included in the present study between January 2010 and March
      2012. All underwent the same surgical operation and rehabilitation protocol. The
      semitendinosus tendon was harvested from the ipsilateral knee. The CC and AC
      ligaments were reconstructed using the graft passed beneath the coracoid and
      through bone tunnels in the clavicle and in the acromion. The graft was secured
      with non-absorbable sutures. Radiographic recurrence of AC joint dislocation was
      the primary outcome. Clinical outcome was assessed using the DASH score and
      normalized Constant score. Wilcoxon's signed-rank test was used for comparison
      between pre- and postoperative results. Significance was set at p <= 0.05.
      RESULTS: the mean follow-up duration was 26.4+/-2.3 months (range: 24-30 months).
      On X-ray evaluation, only two patients (11%) showed asymptomatic recurrence of AC
      joint instability. Comparison between pre- and postoperative DASH and Constant
      scores showed significant clinical improvement (p<0.001). CONCLUSION: anatomical
      reconstruction of CC and AC ligaments using an autologous semitendinosus tendon
      graft for the treatment of AC joint dislocation provided good and reliable
      clinical and radiological results with a low failure rate at short-term follow
      up. LEVEL OF EVIDENCE: level IV, therapeutic case series.

PMID- 25606536
TI  - Conservative integrated treatment of adhesive capsulitis of the shoulder.
AB  - PURPOSE: the aim of this study was to present the results of a conservative
      treatment for adhesive capsulitis based on an original protocol of combined
      pharmacological and rehabilitation treatment. METHODS: fifty-two patients with
      idiopathic adhesive capsulitis were enrolled in the present study. The treatment
      protocol included the use of hyaluronic acid and anaesthetic periarticular and
      intra-articular injections followed by a specific program of capsule and muscle
      stretching. RESULTS: the results of this treatment showed complete recovery of
      range of motion (ROM) in 50 of the 52 cases. The mean pre-treatment ROM values
      were: 85 degrees  for forward elevation, 75 degrees  for abduction, 25 degrees 
      for external rotation, and 15 degrees  for internal rotation. The post-treatment
      mean ROM values showed marked improvements: 175 degrees  for forward elevation,
      175 degrees  for abduction, 87.5 degrees  for external rotation and 75 degrees 
      for internal rotation. CONCLUSIONS: conservative treatment of adhesive capsulitis
      based on a combined pharmacological and rehabilitation approach was found to be
      effective in resolving pain and stiffness in 96% of the patients. LEVEL OF
      EVIDENCE: level IV, therapeutic case series.

PMID- 25606537
TI  - A future in our past: the umbilical cord for orthopaedic tissue engineering.
AB  - The umbilical cord (UC) has recently been added to the list of potential cell
      sources for tissue engineering and regenerative medicine purposes. Although the
      UC is usually discarded after delivery, UC storage in special tissue banks is
      becoming an increasingly common procedure. Indeed, the capacity of UC cells to be
      directed toward different phenotypes makes this tissue an ideal cell source for
      regenerative medicine in orthopedics and in other fields. In this paper, these
      issues are presented and discussed, together with the potential of this cell
      source for allogeneic use. This article also looks at the anatomy of the UC from
      both the macroscopic and the cellular perspective and considers its extraordinary
      potential for research and clinical applications. 

PMID- 25606538
TI  - Degenerative disease in rotator cuff tears: what are the biochemical and
      histological changes?
AB  - The histopathological changes associated with rotator cuff tears include thinning
      and disorganization of collagen fibers, the presence of granulation tissue,
      increased levels of glycosaminoglycans, fibrocartilaginous metaplasia,
      calcification, fatty infiltration, and necrosis of the tendon margin with cell
      apoptosis. The biochemical changes include an increase in the expression of
      matrix metalloproteinases (MMPs) and a decrease in tissue inhibitor of
      metalloproteinases (TIMP) messenger ribonucleic acid expression. Histological
      evidence of tendinopathy has been found in patients with rotator cuff tear.
      Biochemical changes include significant increases in MMP1, MMP2, MMP3, and in
      TIMP1 and TIMP2 levels, not only at the lateral supraspinatus edge, but also in
      the macroscopically intact portion of the supraspinatus tendon and in the intact
      subscapularis. The tissue in the ruptured area of the supraspinatus tendon
      undergoes marked rearrangement at molecular levels. This involves the activity of
      MMP1, 2, and 3 and supports a critical role of MMPs in tendon physiology. Intact
      parts of the torn supraspinatus tendon can present the histopathological changes
      associated with rotator cuff tears. These findings suggest that biochemical
      changes can already occur in a macroscopically intact tendon and seem to point to
      a global degenerative process in the shoulder. 

PMID- 25606539
TI  - Osteochondritis dissecans of the knee.
AB  - Osteochondritis dissecans (OCD) of the knee is a common cause of knee pain and
      dysfunction among skeletally immature and young adult patients. OCD is
      increasingly frequently seen in pediatric, adolescent and young adult athletes.
      If it is not recognized and treated appropriately, it can lead to secondary
      osteoarthritis with pain and functional limitation. Stable lesions in skeletally
      immature patients should initially be managed non-operatively. Unstable juvenile
      lesions and stable juvenile lesions that fail to heal with non-operative
      treatment require a surgical treatment. By contrast, adult OCD of the knee rarely
      responds to conservative measures because of limited healing potential. Operative
      treatment depends on the lesion stage, and there exist several surgical options. 

PMID- 25606540
TI  - Soft tissue balancing in total knee arthroplasty.
AB  - A good outcome in total knee arthroplasty depends on many factors: joint
      alignment, range of motion, patellar tracking and ligament stability. A correct
      soft tissue balance keeps the joint aligned in flexion and extension, and
      therefore constitutes the most important factor for durability of the implant.
      Indeed, incorrect soft tissue balancing is the primary cause of early implant
      failure necessitating revision surgery. Soft tissue releases, serving to correct
      imbalances, are performed until the flexion and extension gaps appear symmetrical
      and balanced. A knee is considered perfectly balanced when the flexion and
      extension gaps are perfectly rectangular and all the measurements are absolutely
      equal. 

PMID- 25606542
TI  - Measures in orthopaedics: what, how and why?

PMID- 25606541
TI  - Extra-articular reconstruction in the anterior cruciate ligament deficient knee:
      a commentary.
AB  - The conclusions of the consensus conference organized in 1989 by the AOSSM in
      Snow mass on the Extra-articular reconstrucions in ACL deficient knee were
      reviewed in the light of the more recent advances in surgical techniques and
      rehabilitation. While most of the statements validated by the experts related to
      the use of ERs used in isolation and in adolescente patients have been confirmed
      by following studies, this paper pointed out that, on the contrary, the use of
      ERs in association with intra-articular reconstruction should be reconsidered and
      should be of great value in selected cases in order to improve knee stability,
      reduce rate of failure with no increased risk of complications and late
      degenerative osteoarthritis. 

PMID- 25606543
TI  - Improving the accuracy of the preoperative diagnosis of long head of the biceps
      pathology: the biceps resisted flexion test.
AB  - PURPOSE: the purpose of this study was to describe a new test for identifying
      lesions of the long head of the biceps (LHB) and to evaluate its diagnostic
      performance in comparison with selected traditional clinical tests. METHODS: one
      hundred and nine consecutive candidates for arthroscopic rotator cuff repair were
      prospectively recruited. The BRF test, which measures biceps resisted flexion
      strength, was performed with the patient seated (armat the side and elbow flexed
      at 90 degrees ). The patient was asked to maintain maximal resistance for five
      seconds while strength was assessed with a digital dynamometer. Since the
      dynamometer expresses a continuous variable in kilograms, the measure was
      dichotomized using a threshold value (cut-off) value-able to simultaneously
      maximize the sensitivity and specificity. This cut-off value was derived from
      receiver operating characteristic (ROC) curve analysis. Speed's test and the
      O'Brien test were also performed. During arthroscopy the presence of LHB
      pathology was assessed. RESULTS: biceps resisted flexion strength was
      significantly higher in patients without associated LHB lesions [median (range):
      3 kg (0-9.5 kg) versus 0 kg (0-8.5 kg); p< 0.001]. The cut-off level able to
      simultaneously maximize the sensitivity and specificity of the test was 1.1kg.
      The area under the ROC curve was 0.745 (p<0.001) for the dichotomic BRF test
      (dBRF), 0.562 (p=0.3) for the O'Brien test, and 0.602 (p=0.113) for Speed's test.
      A significant good level of accuracy was achieved only by the dBRF test.
      Specificity and the positive predictive value were significantly higher for the
      dBRF test than for Speed's and O'Brien's tests (p<0.02). Age and the dBRF test
      were both found to be significant predictors of LHB lesions. CONCLUSIONS: the
      dBRF test showed higher accuracy than traditional clinical tests in diagnosing
      LHB lesions. This novel test for biceps pathology may be advantageous because it
      is objective and therefore likely reproducible. LEVEL OF EVIDENCE: Level II,
      Development of diagnostic test on basis of consecutive patients (with universally
      applied reference "gold" standard).

PMID- 25606544
TI  - Validity and reliability of the SPORTS score for shoulder instability.
AB  - PURPOSE: athletes affected by shoulder instability cannot be judged solely
      according to the criteria used for non-athletes. In order to improve the
      assessment of shoulder instability surgery outcomes, the SPORTS score was tested
      in a cohort of athletes. METHODS: ninety-eight athletes at an average follow-up
      of 4.6 years (range 1-9.2) after open or arthroscopic surgery for recurrent
      anterior shoulder instability were included in this study. The patients were
      asked to complete the SPORTS score questionnaire twice, with an interval of 2-3
      weeks between the two assessments. The Bland-Altman method and the intra-class
      correlation coefficient were used to measure reliability. Criterion validity was
      assessed by calculating the Spearman correlation coefficient between the SPORTS
      score and the Western Ontario Shoulder Instability Index (WOSI) score, the Rowe
      score, the Oxford Shoulder Instability Score (OSIS), and the Subjective Shoulder
      Value (SSV). RESULTS: the SPORTS score showed excellent test-retest reliability.
      The systematic error between the first and the second assessment was 0.3 points
      (95% upper limit of agreement = 2.3 points). The criterion validity was found to
      be strong for the SPORTS score, which correlated best with the SSV and the
      "sport, recreation, and work" component of the WOSI score. The SPORTS score had
      an acceptable floor effect (8%). The ceiling effect was 46%, which was better
      than the ceiling effects seen with the Rowe, OSIS and WOSI scores. CONCLUSIONS:
      this study suggests that the SPORTS score is a valid score in the assessment of
      athletes after surgery for shoulder instability and that it adds important
      information to the currently available scores. LEVEL OF EVIDENCE: Level III,
      diagnostic study of nonconsecutive patients.

PMID- 25606545
TI  - How do massive immobile rotator cuff tears behave after arthroscopic interval
      slides? Comparison with mobile tears.
AB  - PURPOSE: the aim of this study was to compare clinical outcomes of contracted
      immobile massive rotator cuff tears mobilised through an arthroscopic interval
      slide technique versus massive mobile cuff tears directly repaired without any
      mobilisation. METHODS: twenty-five patients who underwent arthroscopic repair for
      massive rotator cuff tears with a minimum of 18 months follow-up were included.
      The patients were retrospectively divided into two groups. In group 1, a single
      or double interval slide was performed to achieve adequate tendon mobilisation.
      In group 2 (control group), massive rotator cuff tears were arthroscopically
      repaired without any additional release. Patients were evaluated with validated
      outcomes scores: subjective and objective Constant score, a Visual Analogue Scale
      (VAS) for pain, and single Assessment Numeric Evaluation (SANE). RESULTS: the two
      groups were comparable in terms of age, gender and involvement of the dominant
      arm. The mean follow-up duration was 31 months in group 1 and 28 months in group
      2 (p = 0.4). The two groups showed no significant differences in SANE and VAS
      results (group 1: SANE 77%, VAS 1.3; group 2: SANE 88%, VAS 1.6), or in total
      Constant score (group 1: 66.5 +/- 11; group 2: 75 +/- 14; p = 0.1) and subjective
      Constant score (Group 1: 31 +/- 5; group 2: 30.8 +/- 7; p = 0.9). A significant
      difference was found for the objective Constant score, which was higher in the
      control group (group 1: 35.5 +/- 7; group 2: 44 +/- 8; p = 0.009). CONCLUSIONS:
      Subjective clinical outcomes of arthroscopic repair with or without interval
      slides did not differ and were satisfactory. Objectively, immobile cuff tears
      showed inferior results. The use of interval slides might be considered a first
      step or an alternative to more invasive procedures for low demanding patients.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 25606546
TI  - Early assessment of patient perception of outcome in total knee replacement.
AB  - PURPOSE: the aim of the present study was to measure patient perception in the
      early period after knee replacement surgery and to correlate health status with
      the surgery-related outcome. METHODS: thirty-eight consecutive patients who
      underwent total knee replacement were evaluated before surgery; at the time
      Radiographic evaluation was used to assess limb alignment and the Oxford Knee
      Score (OKS) to assess objective outcome. Health outcome was measured with the
      three-level version of the EuroQol - five dimension (EQ-5D-3L) self-administered
      questionnaire, a standardized instrument used to measure patient's perception of
      health status. Evaluation was performed before surgery, at discharge from
      hospital, and six weeks after surgery. RESULTS: the mean overall EQ-5D-3L scores
      were 10.23 before surgery, 8.34 at discharge from the hospital, and 6.52 at six
      weeks. The overall EQ-5D-3L score before surgery was greater than 8 points in 31
      of the 38 patients, ranging from 5 to 8 points in 21 of the 38 patients at the
      discharge and greater than 8 points in six of the 38 patients six weeks after
      surgery. Patients with scores of over 8 points at six weeks also scored more than
      10 points on the discharge assessment. CONCLUSIONS: analysis of early patient
      reports of performance after TKR showed marked changes in the level of
      satisfaction during the first six weeks after surgery. An EQ-5D-3L score of 8 or
      more at follow-up should be considered a sign that the patient has not achieved
      satisfaction and, accordingly, should be studied in the context of a personalized
      follow-up schedule in order to identify as soon as possible the causes of
      impairment. LEVEL OF EVIDENCE: Level IV, prognostic case series.

PMID- 25606547
TI  - Analysis of differences in bone removal during femoral box osteotomy for primary
      total knee arthroplasty.
AB  - PURPOSE: this study was conducted to compare the quantity of intercondylar bone
      removed during femoral box osteotomy for implantation of three contemporary
      posterior stabilized (PS) total knee arthroplasty designs: Sigma PS (DePuy),
      Vanguard (Biomet) and Persona (Zimmer). METHODS: we compared the maximum
      volumetric bone resection required for the housing of the PS mechanism of these
      three designs. Bone removal by each PS box cutting jig was three-dimensionally
      measured. The differences between the three designs were analyzed by the Kruskal
      Wallis test. The Mann-Whitney U-test was used for pairwise comparisons. The level
      of significance was set at p<0.05. RESULTS: for small-size implants, the average
      box osteotomy volume of Persona was significantly smaller than the Vanguard and
      Sigma PS volumes (p=0.003). The mean difference between Vanguard and Sigma PS
      (p=0.01) was also significant. For medium size implants, the mean difference
      between Persona and Sigma PS (p=0.008) and the mean difference between Vanguard
      and Sigma PS (p=0.01) were statistically significant. For large size implants,
      the mean difference between Vanguard and Sigma PS (p=0.01) and the mean
      difference between Sigma PS and Persona (p=0.008) were statistically significant.
      CONCLUSIONS: irrespective of implant size, the Persona cutting jig always
      resected significantly less bone than did Vanguard and Sigma PS. CLINICAL
      RELEVANCE: although this study does not establish any clinical relevance of
      removing more or less bone at primary TKA, its results suggest that if a PS
      design is indicated, it is preferable to select a model which resects less distal
      femoral bone.

PMID- 25606548
TI  - The use of braces in the rehabilitation treatment of the post-traumatic elbow.
AB  - The elbow, the middle joint of the upper limb, enables the hand to be placed at
      various distances from the body. The articular, muscular and neuromotor
      complexity of the elbow is such that it is often prone to stiffness, especially
      if immobilized for long periods of time. Therefore, mobilization of the
      posttraumatic elbow must be started early. In the presence of lesions to the
      ligamentous structures, the joint must be protected to prevent these structures
      from being placed under tension during movement. Rehabilitation of the elbow
      includes the use of braces. Different types of brace are used depending on
      clinical situation and the objectives to be achieved. They can have fixed
      protection or locked articulation, allow an adjustable range of movement to
      restrict flexion-extension and pronation-supination, or allow dynamic and static
      progressive movement. The latter plays a special role in conservative treatment
      and following surgical release. However, the effectiveness of braces in the
      rehabilitation treatment of elbow stiffness depends on the patient's compliance.
      Their use requires a considerable amount of physician time to achieve the
      objectives envisaged by the rehabilitation program. 

PMID- 25606549
TI  - Acromioclavicular joint instability: anatomy, biomechanics and evaluation.
AB  - Acromioclavicular (AC) joint instability is a common source of pain and
      disability. The injury is most commonly a result of a direct impact to the AC
      joint. The AC joint is surrounded by a capsule and has an intra-articular
      synovium and an articular cartilage interface. An articular disc is usually
      present in the joint, but this varies in size and shape. The AC joint capsule is
      quite thin, but has considerable ligamentous support; there are four AC
      ligaments: superior, inferior, anterior and posterior. The coracoclavicular (CC)
      ligament complex consists of the conoid and trapezoid ligaments. They insert on
      the posteromedial and anterolateral region of the undersurface of the distal
      clavicle, respectively. The coracoid origin of the trapezoid covers the posterior
      half of the coracoid dorsum; the conoid origin is more posterior on the base of
      the coracoid. Several biomechanical studies showed that horizontal stability of
      the AC joint is mediated by the AC ligaments while vertical stability is mediated
      by the CC ligaments. The radiographic classification of AC joint injuries
      described by Rockwood includes six types: in type I injuries the AC ligaments are
      sprained, but the joint is intact; in type II injuries, the AC ligaments are
      torn, but the CC ligaments are intact; in type III injuries both the AC and the
      CC ligaments are torn; type IV injuries are characterized by complete dislocation
      with posterior displacement of the distal clavicle into or through the fascia of
      the trapezius; type V injuries are characterized by a greater degree of soft
      tissue damage; type VI injuries are inferior AC joint dislocations into a
      subacromial or subcoracoid position. The diagnosis of AC joint instability can be
      based on historical data, physical examination and imaging studies. The cross
      body adduction stress test has the greatest sensitivity, followed by the AC
      resisted extension test and the O'Brien test. Proper radiographic evaluation of
      the AC joint is necessary. The Zanca view is the most accurate view for examining
      the AC joint. The axial view of the shoulder is important in differentiating a
      type III AC joint injury from a type IV injury. 

PMID- 25606550
TI  - Posterolateral rotatory instability of the knee after arthroscopic subtotal
      lateral meniscectomy: a case report.
AB  - A 33-year-old Caucasian woman came to our attention complaining of lateral knee
      pain on the left side, severe external instability associated with varus
      malalignment, and difficulties in weight-bearing activities. The symptoms had
      appeared following two lateral meniscectomies on her discoid meniscus, performed
      elsewhere. The patient was initially submitted to an allograft meniscus
      transplantation exploiting the unloaded condition of lateral compartment and
      obtained pain relief. The posterolateral corner was reconstructed in combination
      with a valgus osteotomy to address the posterolateral rotatory instability. The
      follow-up assessment at two years after the last surgery showed no symptoms,
      maintenance of limb alignment and no evidence of joint degeneration. 

PMID- 25606551
TI  - 50 up! Our vision and dream for our "orange journal".

PMID- 25606552
TI  - Treatment of osteochondritis dissecans of the knee with a biomimetic scaffold. A
      prospective multicenter study.
AB  - PURPOSE: the aim of the present study was to evaluate the clinical outcome of the
      treatment of osteochondritis dissecans (OCD) of the knee with a type-I collagen
      hydroxyapatite nanostructural biomimetic osteochondral scaffold. METHODS: twenty
      three patients affected by symptomatic knee OCD of the femoral condyles, grade 3
      or 4 of the International Cartilage Repair Society (ICRS) scale, underwent
      biomimetic scaffold implantation. The site of the defect was the medial femoral
      condyle in 14 patients, whereas in 9 patients the lateral femoral condyle was
      involved. The average size of the defects was 3.5+/-1.43 cm(2). All patients were
      clinically evaluated using the ICRS subjective score, the IKDC objective score,
      the EQ-VAS and the Tegner Activity Score. Minimum follow-up was two years. MRI
      was performed at 12 and 24 months after surgery and then every 12 months
      thereafter. RESULTS: the ICRS subjective score improved from the baseline value
      of 50.93+/-20.6 to 76.44+/-18.03 at the 12 months (p<0.0005) and 82.23+/- 17.36
      at the two-year follow-up (p<0.0005). The IKDC objective score confirmed the
      results. The EQ-VAS showed a significant improvement from 3.15+/-1.09 to 8.15+/
      1.04 (p<0.0005) at two years of follow-up. The Tegner Activity Score improvement
      was statistically significant (p<0.0005). CONCLUSIONS: biomimetic scaffold
      implantation was a good procedure for treating grade 3 and 4 OCD, in which other
      classic techniques are burdened by different limitations. This open one-step
      surgery gave promising stable results at short-term follow-up. LEVEL OF EVIDENCE:
      Level IV, therapeutic case series.

PMID- 25606553
TI  - Long-term outcome of low contact stress total knee arthroplasty with different
      mobile bearing designs.
AB  - PURPOSE: to evaluate the differences in clinical outcome and survivorship of
      three different mobile bearings for total knee arthroplasty. METHODS: a
      retrospective study was conducted in 60 patients (53 females, 7 males, mean age:
      68 years and 5 months) each submitted to total knee replacement using one of the
      three different mobile bearings of the LCS system (Depuy Johnson & Johnson,
      Warsaw, IN). The diagnosis was knee osteoarthritis in 57 cases and rheumatoid
      arthritis in three cases. Three different groups of 20 cases each were
      identified: total knee arthroplasties with mobile menisci (group 1); total knee
      arthroplasties with the rotating platform (group 2); and total knee
      arthroplasties with the anteroposterior glide platform (group 3). As regards the
      component fixation, 33 implants were cementless, three were cemented, and in 24
      only the tibial component was cemented. The patella was not replaced. RESULTS:
      although the duration of follow-up differed between the three groups, the
      clinical and radiological results at final follow-up showed no revision of
      femoral and/or tibial components for mechanical or septic reasons, and no signs
      of impending failure. One meniscal bearing, showing polyethylene wear after 17
      years, was successfully replaced. CONCLUSIONS: the present retrospective study
      confirmed the long-term effectiveness of knee implants with mobile bearings, in
      which the congruity of the surfaces makes it possible to overcome the problem of
      high contact stresses that may result in polyethylene wear and osteolysis; at the
      same time, these implants eliminate constraint forces thereby reducing the risk
      of mechanical loosening. LEVEL OF EVIDENCE: Level III, retrospective comparative
      study.

PMID- 25606554
TI  - Osteochondritis dissecans of the talus.
AB  - Osteochondritis dissecans (OCD) is an acquired idiopathic lesion of subchondral
      bone that can produce delamination and sequestration with or without articular
      cartilage involvement and instability. The cause of OCD is still debated: the
      most recognized etiology is the occurrence of repetitive micro-traumas associated
      with vascular impairment, causing progressive ankle pain and dysfunction in
      skeletally immature and young adult patients. Ankle OCD is classically located in
      the medial part of the talus, while lateral and posterior involvement is less
      frequent. Diagnosis of OCD, based on MRI findings, is quite straightforward; MRI
      examination can also be very useful for dating the defect and obtaining
      information about the associated bone bruise. Osteochondritis dissecans, if not
      recognized and treated appropriately, may lead to secondary osteoarthritis with
      pain and functional limitation. Surgical treatment is mandatory especially in
      young patients with unstable cartilage fragments. There are various surgical
      options: fixation, microfracture, or substitution using autologous chondrocyte
      implantation techniques. 

PMID- 25606555
TI  - Inertial sensors to quantify the pivot shift test in the treatment of anterior
      cruciate ligament injury.
AB  - The main purpose of this article was to describe in detail, from the perspective
      of the clinical end user, a previously presented non-invasive methodology,
      applied in the treatment of anterior cruciate ligament injury, in which inertial
      sensors are used to quantify the pivot shift test. The outcomes obtained and
      relative considerations were compared with findings emerging from a review of the
      relevant updated literature. The detailed description here provided covers the
      system, the parameters identified and the testing procedure; it also includes the
      technical specifications of the hardware, the features introduced in the updated
      version of the software and the application of the system in clinical practice.
      The comparison of the technical considerations and clinical results with the
      updated literature confirmed the system's optimal ergonomics, good
      reproducibility and clinical reliability. The novel approach here analyzed has
      been shown to overcome the weaknesses of other available devices and systems.
      Therefore, since it can be considered a new paradigm in the quantification of
      pivot shift test, we can recommend its routine use in clinical practice. 

PMID- 25606556
TI  - Calcific tendinitis of the shoulder.
AB  - Calcific tendinitis is a common disease that predominantly affects individuals
      aged between 40 and 60 years. Women seem to be more affected than men. Various
      factors have been suggested to play a role in this condition, such as abnormal
      activity of the thyroid gland, metabolic diseases (e.g. diabetes), and genetic
      predisposition. Various etiological hypotheses have been advanced: the
      degenerative and multiphasic theories are the two most accredited ones.
      Clinically, calcific tendinitis is characterized by severe, disabling pain which
      occurs spontaneously, usually in the morning. There can be concomitant stiffness,
      giving rise to a frozen shoulder-like clinical picture. Conventional radiography
      of the shoulder is the most appropriate imaging approach. Most cases resolve
      spontaneously. Many conservative treatments have been reported in the literature,
      showing varying levels of evidence of efficacy. Arthroscopic surgery is the
      orthopedic specialist's last option. It is to be noted that post-surgical pain
      can persist for many weeks after the operation. Finally, it is important not to
      forget the variant characterized by osteolytic involvement of the greater
      tuberosity, which has been associated with a worse clinical outcome, both after
      conservative treatment and after surgery. 

PMID- 25606557
TI  - Imaging of articular cartilage: current concepts.
AB  - Magnetic resonance imaging (MRI) is the gold standard method for non-invasive
      assessment of joint cartilage, providing information on the structure, morphology
      and molecular composition of this tissue. There are certain minimum requirements
      for a MRI study of cartilage tissue: machines with a high magnetic field (> 1.5
      Tesla); the use of surface coils; and the use of T2-weighted, proton density
      weighted fast-spin echo (T2 FSE-DP) and 3D fat-suppressed T1-weighted gradient
      echo (3D-FS T1W GRE) sequences. For better contrast between the different joint
      structures, MR arthography is a method that can highlight minimal fibrillation or
      fractures of the articular surface and allow evaluation of the integrity of the
      native cartilage-repair tissue interface. To assess the biochemical composition
      of cartilage and cartilage repair tissue, various techniques have been proposed
      for studying proteoglycans [dGEMRIC, T1rho mapping, sodium (23Na) imaging MRI,
      etc.], collagen, and water distribution [T2 mapping, "magnetisation transfer
      contrast", diffusion-weighted imaging (DWI), and so on]. Several MRI
      classifications have been proposed for evaluating the processes of joint
      degeneration (WORMS, BLOKS, ICRS) and post-surgical maturation of repair tissue
      (MOCART, 3D MOCART). In the future, isotropic 3D sequences set to improve image
      quality and facilitate the diagnosis of disorders of articular structures
      adjacent to cartilage. 

PMID- 25606558
TI  - First patellar dislocation: from conservative treatment to return to sport.
AB  - Treatment of first patellar dislocation is usually conservative and the
      subsequent rehabilitation program is based on specifically formulated objectives,
      which can be divided into different stages: stage 1: resolution of pain, swelling
      and inflammation; stage 2: recovery of joint motion and flexibility; stage 3:
      recovery of muscle strength; stage 4: recovery of motor patterns and
      coordination; and stage 5: recovery of the sport-specific athletic action and
      return to sporting activity. The aim, in the management of a patient affected by
      first patellar dislocation, is to achieve the best possible functional recovery:
      since this is a condition often affecting young athletes, this means returning
      them to their pre-injury conditions, both in terms of fitness and the level of
      sporting activity practiced. By proceeding through functional stages, the risk of
      recurrence of the dislocation can be reduced. The "go-ahead" to resume sporting
      activity can only be given in the presence of normal results on sport-specific
      functional tests. 

PMID- 25606559
TI  - Locked bilateral posterior fracture-dislocation of the shoulder in an epileptic
      patient: case report.
AB  - Bilateral posterior dislocation of the shoulder, often secondary to seizures, is
      uncommon, while bilateral posterior fracture-dislocations is rarer still: 0.6
      cases among a population of 100,000 people per year. The scientific literature
      contains very few published reports of cases of bilateral posterior fracture
      dislocation of the shoulder, a condition that tends to be sustained by epileptic
      patients during seizures. The authors presented a case of bilateral posterior
      fracture-dislocation of the shoulder secondary to a first epileptic seizure
      episode treated by humeral head replacement with stem less implants on both
      shoulders, with satisfactory radiographic and clinical outcome. 

PMID- 25606561
TI  - Efficacy of Long-Term Daily Dosage of Alfuzosin 10 mg upon Sexual Function of
      Benign Prostatic Hypertrophy Patients: Two-Year Prospective Observational Study.
AB  - PURPOSE: To identify sexual function improvement associated with alfuzosin (10 mg
      daily for 2 years). MATERIALS AND METHODS: We enrolled 30 men with lower urinary
      tract symptom (LUTS) who visited Gyeongsang National University Hospital between
      2010 and 2012. At first visit, urinalysis, prostate specific antigen, transrectal
      ultrasound, and uroflowmetry were performed. The nternational Prostate Symptom
      Score (IPSS), quality of life (QoL), International Index of Erectile Function
      (IIEF), and Male Sexual Health Questionnaire Ejaculation Function Domain (MSHQ
      EjFD) questionnaires were administered, and the subjects answered the same
      questionnaires at 1 month, 6 months, 1 year, and 2 years of follow-up. RESULTS:
      Twelve men completed of the entire study. After administration of alfuzosin, the
      median IPSS at first visit, 1 month, 6 months, 1 year, and 2 years was 18.00
      (interquatile range [IQR]: 14.00~29.75), 20.00 (IQR: 11.50~30.00), 15.50 (IQR:
      8.50~25.25), 14.50 (IQR: 9.25~19.50), and 11.50 (IQR: 5.00~17.75), respectively,
      which showed an improvement. The median QoL at the same times was 4.50 (IQR:
      4.00~5.00), 4.50 (IQR: 4.00~5.00), 3.00 (IQR: 2.00~4.00), 3.50 (IQR: 2.25~4.00),
      and 3.00 (IQR: 1.00~3.00), respectively, and also showed improvement. Likewise,
      the median IIEF was 36.50 (IQR: 24.50~46.75), 37.50 (IQR: 26.75~47.25), 45.50
      (IQR: 35.00~59.75), 48.50 (IQR: 34.75~62.75), and 47.50 (IQR: 43.25~61.00), while
      the median MSHQ-EjFD was 19.00 (IQR: 12.0~24.75), 19.50 (IQR: 13.50~27.75), 23.00
      (IQR: 19.25~32.25), 26.50 (IQR: 18.25~34.50), 27.00 (IQR: 21.50~32.50),
      respectively, with both showing improvement. CONCLUSIONS: After administration of
      alfuzosin (10 mg daily for 2 years), the IPSS, QoL, IIEF, and MSHQ-EjFD all
      improved significantly. This means long-term administration of 10 mg of alfuzosin
      daily would be effective not only for LUTS but also erectile function and
      ejaculation.

PMID- 25606560
TI  - Understanding the role of heat shock protein isoforms in male fertility, aging
      and apoptosis.
AB  - Heat shock proteins (HSPs) play a role in the homeostasis, apoptosis regulation
      and the maintenance of the various other physiological processes. Aging is
      accompanied by a decrease in the resistance to environmental stress, while
      mitochondria are primary targets in the process of aging, their expression
      decreasing with age. Mitochondrion also plays a significant role in the process
      of spermatogenesis. HSPs have been shown to be involved in apoptosis with some of
      acting as apoptotic inhibitors and are involved in cytoprotection. In this review
      we discuss the roles of Hsp 27, 60, 70, and 90 in aging and male infertility and
      have concluded that these particular HSPs can be used as a molecular markers for
      mitochondrially- mediated apoptosis, aging and male infertility. 

PMID- 25606562
TI  - Relationship between Serum Testosterone and Cardiovascular Disease Risk
      Determined Using the Framingham Risk Score in Male Patients with Sexual
      Dysfunction.
AB  - PURPOSE: The aim of the present study aimed to evaluate the effect of
      testosterone on cardiovascular disease by using the Framingham Risk Score (FRS)
      in patients with sexual dysfunction. MATERIALS AND METHODS: A total of 308 men
      with sexual dysfunction were enrolled in this study. Clinical assessments
      included the 15-item International Index of Erectile Function (IIEF), blood
      pressure measurement, and clinical laboratory indexes. The FRS, which predicts
      the incidence rate of cardiovascular diseases in the next 10 years, was
      calculated on the basis of age, gender, total cholesterol, smoking status, high
      density lipoprotein cholesterol, and systolic blood pressure. RESULTS: The mean
      age of the 308 enrolled patients was 49.42+/-10.73 years, and the patients' mean
      body mass index (kg/m(2)) was 25.07+/-3.14. The mean total IIEF score was 28.44+/
      18.06. The median total testosterone concentration was 3.2 ng/mL (interquartile
      range [IQR]: 2.3~3.2 ng/mL). The median calculated free and bioavailable
      testosterone concentrations were 0.052 ng/mL (IQR 0.039~0.070 ng/mL) and 1.30
      ng/mL (IQR: 1.00~1.76 ng/mL), respectively. The mean FRS was 10.47+/-6.45. The
      FRS tended to show a negative correlation with the total and calculated free
      testosterone levels, but this was not significant (p=0.064 and p=0.074,
      respectively). In the multiple linear regression analysis, a significant negative
      correlation was observed between the total testosterone level and the FRS
      (p=0.048). CONCLUSIONS: The results suggest that the testosterone level is
      related to the FRS and that a high testosterone level may decrease the risk of
      cardiovascular disease.

PMID- 25606563
TI  - The efficacy of mirodenafil for chronic prostatitis/chronic pelvic pain syndrome
      in middle-aged males.
AB  - PURPOSE: The aim of this study was to investigate the efficacy of mirodenafil in
      middle-aged male patients with chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS). MATERIALS AND METHODS: Eighty-eight males with CP/CPPS were randomized
      to receive either levofloxacin (500 mg/d) (group L, 40 patients) or levofloxacin
      (500 mg/d) and mirodenafil (50 mg/d) (group ML, 48 patients) for six weeks. The
      International Prostate Symptom Score (IPSS), National Institutes of Health
      Chronic Prostatitis Symptom Index (NIH-CPSI), and erectile function (EF) domain
      scores of the International Index of Erectile Function (IIEF) questionnaire were
      used to grade symptoms at baseline and 6 weeks after treatment. RESULTS: The mean
      change in total IPSS from baseline was higher in group ML than that in group L
      (group L, -1.1 vs. group ML, -4.3; p<0.05). Significant improvements were also
      seen in the IPSS voiding subscore (group L, -0.7 vs. group ML, -3.0; p<0.05).
      Changes observed in the NIH-CPSI of group ML at six weeks were greater than those
      at baseline (group L, -3.2 vs. group ML, -7.2; p<0.05). Significant improvements
      were seen in the NIH-CPSI voiding (group L, -0.5 vs. group ML, -1.7; p<0.05) and
      quality of life domains (group L, -1.0 vs. group ML, -1.8; p<0.05). Group ML
      showed a significantly greater increase in the IIEF-EF score than did group ML
      (group L, +0.2 vs. group ML, +7.8; p<0.05). CONCLUSIONS: Mirodenafil (50 mg once
      daily) was well tolerated and resulted in significant symptomatic improvement in
      middle-aged males with CP/CPPS.

PMID- 25606564
TI  - Effects of Hydro-Alcoholic Extract of Rhus coriaria (Sumac) Seeds on Reproductive
      Complications of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male
      Mice.
AB  - PURPOSE: The purpose of this study was to investigate the effects of the hydro
      alcoholic extract of Rhus coriaria seeds on the reproductive system of
      nicotinamide-streptozotocin-induced type-2 diabetic mice. MATERIALS AND METHODS:
      In this experimental study, 56 male Naval Medical Research Institute mice were
      randomly divided into seven groups (n=8): control; diabetic mice; diabetic mice
      administered glibenclamide (0.25 mg/kg); diabetic mice who received the hydro
      alcoholic extract of R. coriaria seeds (200 and 400 mg/kg groups); and normal
      mice who received this extract (200 and 400 mg/kg groups). Diabetes was induced
      by intraperitoneal administration of streptozotocin (65 mg/kg) 15 minutes after
      an injection of nicotinamide (120 mg/kg). Then, glibenclamide and the above
      mentioned extract were administered orally for 28 consecutive days. Twenty-four
      hours after the last treatment, serum samples, the testes, and the cauda
      epididymis were removed immediately for hormonal, testis morphology, and sperm
      parameter assessments. RESULTS: Body and testicular weight, sperm count and
      viability, and serum luteinizing hormone, follicle-stimulating hormone and
      testosterone levels were significantly lower in the diabetic mice (p<0.05). The
      diabetic mice treated with 400 mg/kg of the hydro-alcoholic extract of R.
      coriaria seeds recovered from these reductions (p<0.05). Further, glibenclamide
      alleviated hormonal and sperm count depletion in diabetes-induced mice (p<0.05).
      CONCLUSIONS: The present results indicated that the hydro-alcoholic extract of R.
      coriaria seeds has anti-infertility effects in diabetic males.

PMID- 25606565
TI  - Primary androgen deprivation therapy for prostate cancer in koreans: a
      retrospective multicenter study.
AB  - PURPOSE: To evaluate the characteristics of patients who received primary
      androgen deprivation therapy (PADT) for prostate cancer and the clinical efficacy
      of this treatment. MATERIALS AND METHODS: Two hundred forty patients treated by
      PADT were reviewed. These patients could not receive definitive therapy owing to
      old age, patient need, and medical comorbidity. The patients were divided into
      three groups according to the extent of prostate cancer: localized, locally
      advanced, and metastatic. Then, prostate-specific antigen (PSA) progression in
      these groups was analyzed. RESULTS: The median age of the patients was 73.0
      years, and the median pretreatment PSA level was 47.0 ng/mL. Of the patients,
      91.7% were treated with combined androgen blockade, and 8.3% were treated with
      monotherapy. Clinical factors for PSA progression were a PSA nadir and a high
      clinical stage. Estimated PSA recurrence-free median survival time in each group
      was 57, 24, and 12 months, respectively. A PSA nadir of >0.2 ng/mL and metastatic
      stage were independent factors for expecting a poor response to PADT (hazard
      ratio 4.26, p<0.001; and 2.60, p<0.001). CONCLUSIONS: Patients with localized or
      locally advanced prostate cancer who did not receive definitive therapy had lower
      PSA progression rates than those at metastatic stage during PADT. Further, a PSA
      nadir of <=0.2 ng/mL showed better progression-free survival. Therefore, PADT can
      be another therapeutic option in well-selected patients with localized or locally
      advanced prostate cancer and PSA change should be checked carefully.

PMID- 25606566
TI  - Meta-Analysis of the Relationship between CXCR4 Expression and Metastasis in
      Prostate Cancer.
AB  - PURPOSE: Experimental studies have suggested that the stromal-derived factor-1
      (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in
      several malignancies. We performed a meta-analysis to elucidate the relationship
      between CXCR4 expression and the clinicopathological features of prostate cancer.
      MATERIALS AND METHODS: Data were collected from studies comparing Gleason score,
      T stage, and the presence of metastasis with CXCR4 levels in human prostate
      cancer samples. The studies were pooled, and the odds ratio (OR) of CXCR4
      expression for clinical and pathological variables was calculated. RESULTS: Five
      articles were eligible for the current meta-analysis. We found no relationship
      between CXCR4 expression and Gleason score (<7 vs. >=7). The forest plot using
      the fixed-effects model indicated an OR of 1.585 (95% confidence interval [CI]:
      0.793~3.171; p=0.193). Further, CXCR4 expression was not associated with the T
      stage (<T3 vs. >=T3), and the relevant meta-analysis showed OR=1.803 (95% CI:
      0.756~4.297, p=0.183). However, increased CXCR4 expression was strongly
      associated with metastatic disease with a fixed-effects pooled OR of 7.459 (95%
      CI: 2.665~20.878, p<0.001). CONCLUSIONS: Our meta-analysis showed that the higher
      CXCR4 protein expression in prostate cancer specimens is significantly associated
      with the presence of metastatic disease. This supports previous experimental data
      supporting the role played by the SDF-1/CXCR4 axis in metastasis.

PMID- 25606567
TI  - Effects of exendin-4 on male reproductive parameters of d-galactose induced aging
      mouse model.
AB  - PURPOSE: The purpose of this study was to evaluate the role of exendin-4 on
      reproductive alteration in a D-galactose-induced aging mouse model. MATERIALS AND
      METHODS: In this experimental study, 72 male Naval Medical Research Institute
      mice (20~25 g) were randomly divided into six groups: control, exendin-4 (1
      nmol/kg), exendin-4 (10 nmol/kg), D-galactose (500 mg/kg), D-galactose+exendin-4
      (1 nmol/kg), and D-galactose+exendin-4 (10 nmol/kg). The aging model animals were
      gavaged with D-galactose for six weeks, and exendin-4 was injected
      intraperitoneally in the last 10 days. At the end of treatment serum luteinizing
      hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were
      evaluated and the cauda epididymis and testis were removed to analyze the sperm
      count and testis morphology. RESULTS: The testis weight and volume decreased in
      the D-galactose group (p<0.01 and p<0.05) respectively. Exendin-4 (1, 10 nmol/kg)
      increased these parameters in the normal and aging mouse models. Serum LH and FSH
      levels increased and the sperm count decreased in the D-galactose group (p<0.05).
      Further, exendin-4 (1 nmol/kg) decreased LH and FSH levels and increased the
      serum testosterone level and sperm count in both normal and aging animals.
      CONCLUSIONS: D-galactose can induce aging alternations in the male reproductive
      system such as decreased sperm count and increased serum LH and FSH levels
      through reactive oxygen species over production and reduced antioxidant enzyme
      activity. Further, co-administration of exendin-4 reduced reproductive
      complications of D-galactose in an aging mouse model.

PMID- 25606568
TI  - Diagnosis of a gastrointestinal stromal tumor presenting as a prostatic mass: a
      case report.
AB  - Gastrointestinal stromal tumors (GISTs) are an unusual and heterogeneous group of
      spindle cell tumors that can also appear on the exterior of the gastrointestinal
      tract (extra-GISTs). Despite the fact that extra-GISTs or large rectal GISTs can
      lead to the clinical impression of a prostatic mass, these tumors are, in
      general, excluded in the differential diagnosis of spindle cell tumors observed
      on prostate needle biopsy. Here, we present, in detail, a case of an extra-GIST
      identified on prostatic biopsy; the tumor was previously believed to be a primary
      prostatic stromal sarcoma in the differential diagnosis. Every investigator
      should check for KIT (CD117) in immunohistochemical staining to rule out an extra
      GIST prior to diagnosing a solitary prostatic tumor, specialized prostatic
      stromal tumor, or leiomyosarcoma on prostate needle biopsy. 

PMID- 25606569
TI  - An unexpected course after simultaneous urethral repair and reimplantation of
      penile prosthesis in a patient with a urethral stricture.
AB  - We experienced the growth of urethral hair along the urethral stricture six years
      after simultaneous urethral repair and reimplantation of penile prosthesis (RPP)
      in a patient with a urethral stricture. We detected hair in the urethra with a
      stricture on the bulbous urethra. Further, we performed hair removal by using a
      pair of cystoscopic forceps and internal urethrotomy. Then, we performed RPP, and
      the patient voided well; the prosthesis worked very well and without any
      complications. One-stage urethroplasty with a pedicle island of the penile skin
      and RPP in a simultaneous stage may be an option for treating the long-segment
      urethral stricture in the penile prosthesis patient. However, we should pay
      attention to the urethral hair growth that can occur after urethral repair
      performed using a skin graft. 

PMID- 25606570
TI  - Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano
      Growth Factor Delays Decompensation Following Myocardial Infarction.
AB  - Insulin like growth factor-I (IGF-1) isoforms differ structurally in their E
      domain regions and their temporal expression profile in response to injury. We
      and others have reported that Mechano-growth factor (MGF), which is equivalent to
      human IGF-1c and rodent IGF-1Eb isoforms, is expressed acutely following
      myocardial infarction (MI) in the mouse heart. To examine the function of the E
      domain region, we have used a stabilized synthetic peptide analog corresponding
      to the unique 24 amino acid region E-domain of MGF. Here we deliver the human MGF
      E-domain peptide to mice during the acute phase (within 12 hours) and the chronic
      phase (8 weeks) post-MI. We assessed the impact of peptide delivery on cardiac
      function and cardiovascular hemodynamics by pressure-volume (P-V) loop analysis
      and gene expression by quantitative RT-PCR. A significant decline in both
      systolic and diastolic hemodynamics accompanied by pathologic hypertrophy
      occurred by 10 weeks post-MI in the untreated group. Delivery of the E-domain
      peptide during the acute phase post-MI ameliorated the decline in hemodynamics,
      delayed decompensation but did not prevent pathologic hypertrophy. Delivery
      during the chronic phase post-MI significantly improved systolic function,
      predominantly due to the effects on vascular resistance and prevented
      decompensation. While pathologic hypertrophy persisted there was a significant
      decline in atrial natriuretic factor (ANF) expression in the E-domain peptide
      treated hearts. Taken together our data suggest that administration of the MGF E
      domain peptide derived from the propeptide form of IGF-1Ec may be used to
      facilitate the actions of IGF-I produced by the tissue during the progression of
      heart failure to improve cardiovascular function.

PMID- 25606571
TI  - Advanced methods of microscope control using MUManager software.
AB  - MUManager is an open-source, cross-platform desktop application, to control a
      wide variety of motorized microscopes, scientific cameras, stages, illuminators,
      and other microscope accessories. Since its inception in 2005, MUManager has
      grown to support a wide range of microscopy hardware and is now used by thousands
      of researchers around the world. The application provides a mature graphical user
      interface and offers open programming interfaces to facilitate plugins and
      scripts. Here, we present a guide to using some of the recently added advanced
      MUManager features, including hardware synchronization, simultaneous use of
      multiple cameras, projection of patterned light onto a specimen, live slide
      mapping, imaging with multi-well plates, particle localization and tracking, and
      high-speed imaging.

PMID- 25606574
TI  - Hypofractionated radiation therapy for prostate cancer: biologic and technical
      considerations.
AB  - The optimal radiation schedule for the curative treatment of prostate cancer is
      not known. The dose-response of tumors and normal tissues to fractionated
      irradiation can be described according to a parameter called the alpha-beta ratio
      (alpha/beta). In the past several years numerous reports have been published that
      suggest that the alpha-beta ratio for prostate cancer may be quite low; between 1
      and 3. If this hypothesis is true, then a radiation therapy schedule that employs
      less frequent and larger fractions, termed hypofractionation, may be more
      efficacious. Multiple randomized trials have been conducted comparing moderate
      (less than 5 Gy/day) hypofractionated radiation therapy and standard radiation
      therapy in men with prostate cancer. In the majority of these studies the
      moderate hypofractionated arm had equivalent efficacy with a similar or improved
      side effect profile. One area to use caution may be in patients with compromised
      (IPSS > 12) urinary function at baseline due to an increase in urinary toxicity
      observed in patients treated with hypofractionated radiation in one study.
      Extreme hypofractionation (greater than or equal to 5 Gy/day), is currently being
      compared in a randomized trial. Early prospectively collected data from multiple
      institutions demonstrates efficacy and toxicity that compares favorably with
      historical controls. The cost savings from hypofractionation could be profound on
      a national level and only increases the necessity of testing hypofractionated
      treatment schedules. Long term data and future trials will help radiation
      oncologists determine the ideal fractionation scheme based on cost, efficacy, and
      toxicity. 

PMID- 25606573
TI  - Neuroendocrine differentiation of prostate cancer: a review.
AB  - Neuroendocrine cells are one of the epithelial populations in the prostate.
      Neuroendocrine differentiation (NED) has been observed in prostate cancer. In
      addition to small cell neuroendocrine carcinomas and carcinoid tumors of the
      prostate, prostatic adenocarcinomas may have NED. The incidence and clinical
      relevance of NED in prostatic adenocarcinoma is not clearly understood because of
      conflicting results in the reported studies, and evaluation of NED is not
      routinely performed in clinical practice. This review is an overall synthesis
      with an aim to develop a more comprehensive understanding and practical approach
      towards the current knowledge of neuroendocrine differentiation. In this review
      we are stratifying these lesions into separate subtypes based on histologic
      parameters such as tumor morphology, neuroendocrine cell density and distribution
      and clinical parameters. We also want to identify current controversies and
      confusing issues not totally resolved in this topic for further investigations.
      Eventually a clearer understanding of this phenomenon and appropriate handling
      NED in prostate cancer will benefit clinical practice. 

PMID- 25606572
TI  - Chromatin Memory in the Development of Human Cancers.
AB  - Cancer is a complex disease with acquired genomic and epigenomic alterations that
      affect cell proliferation, viability and invasiveness. Almost all the epigenetic
      mechanisms including cytosine methylation and hydroxymethylation, chromatin
      remodeling and non-coding RNAs have been found associate with carcinogenesis and
      cancer specific expression profile. Altered histone modification as an epigenetic
      hallmark is frequently found in tumors. Understanding the epigenetic alterations
      induced by carcinogens or infectious agents may help us understand early
      epigenetic changes prior to the development of cancer. In this review, we focus
      on chromatin remodeling and the associated histone modifiers in the development
      of cancer; the application of these modifiers as a cancer therapy target in
      different clinical trial phases is also discussed.

PMID- 25606575
TI  - Emerging players in prostate cancer: long non-coding RNAs.
AB  - Recent observations of novel long non-coding RNAs (lncRNAs) have considerably
      altered our understanding of cell biology. The role of lncRNAs as tumor
      suppressors or oncogenes has been extensively studied. Over-expression of
      oncogenic lncRNAs promotes tumor-cell proliferation and metastasis through
      chromatin looping and distal engagement with the androgen receptor, anti-sense
      gene regulation, alternative splicing, and impeding DNA repair. Prostate cancer
      is the most common type of cancer and frequent cause of cancer-related mortality
      in men worldwide. Unraveling the molecular and biological processes that
      contribute to prostate cancer development and progression is a challenging task.
      In prostate cancer, aberrant expression of lncRNAs has been associated with
      disease progression. In this review, we highlight the emerging impact of lncRNAs
      in prostate cancer research, with a particular focus on the mechanisms and
      functions of lncRNAs. Increased research on lncRNAs will lead to a greater
      understanding of prostate cancercinogenesis and progression and may lead to novel
      clinical applications. LncRNAs have great potential to become new biomarkers for
      detection, prognostication and prediction in prostate cancer. 

PMID- 25606576
TI  - Methoxyacetic acid suppresses prostate cancer cell growth by inducing growth
      arrest and apoptosis.
AB  - Methoxyacetic acid (MAA) is a primary metabolite of ester phthalates that are
      used in production of consumer products and pharmaceutical products. MAA causes
      embryo malformation and spermatocyte death through inhibition of histone
      deacetylases (HDACs). Little is known about MAA's effects on cancer cells. In
      this study, two immortalized human normal prostatic epithelial cell lines (RWPE-1
      and pRNS-1-1) and four human prostate cancer cell lines (LNCaP, C4-2B, PC-3, and
      DU-145) were treated with MAA at different doses and for different time periods.
      Cell viability, apoptosis, and cell cycle analysis were performed using flow
      cytometry and chemical assays. Gene expression and binding to DNA were assessed
      using real-time PCR, Western blot, and chromatin immunoprecipitation analyses. We
      found that MAA dose-dependently inhibited prostate cancer cell growth through
      induction of apoptosis and cell cycle arrest at G1 phase. MAA-induced apoptosis
      was due to down-regulation of the anti-apoptotic gene baculoviral inhibitor of
      apoptosis protein repeat containing 2 (BIRC2, also named cIAP1), leading to
      activation of caspases 7 and 3 and turning on the downstream apoptotic events.
      MAA-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21
      expression at the early time and down-regulation of cyclin-dependent kinase 4
      (CDK4) and CDK2 expression at the late time. MAA up-regulated p21 expression
      through inhibition of HDAC activities, independently of p53/p63/p73. These
      findings demonstrate that MAA suppresses prostate cancer cell growth by inducing
      growth arrest and apoptosis, which suggests that MAA could be used as a potential
      therapeutic drug for prostate cancer. 

PMID- 25606578
TI  - Active surveillance for prostate cancer: a legal perspective.
AB  - Active surveillance (AS) for prostate cancer (PCa) has become a viable management
      strategy for men with low-risk PCa. With AS being offered more often and more
      patients being included in AS studies, the aim of this paper is to describe AS
      from a legal perspective. What might be pitfalls in the management strategy that
      urologists should be aware of? In order to construct an answer to our research
      question, a patient from the Prostate cancer Research International: Active
      Surveillance (PRIAS) study will be used as an example. In the methods section,
      first some information on the PRIAS study is given. Then a PRIAS case will be
      described after which the Dutch legal framework will be set-out. Finally, the
      Dutch legal framework will be applied to the PRIAS case to find what would happen
      if that particular patient would file a complaint. On the basis of the analysis
      we can conclude that urologists that offer AS should be aware of the information
      that they provide to patients when entering AS but also during follow-up. It is
      furthermore important that urologists act in line with their medical professional
      standards. Therefore it is advised that urologists follow the progress that is
      made within the field of AS carefully, as the field is moving rapidly. 

PMID- 25606577
TI  - Beta-catenin is elevated in human benign prostatic hyperplasia specimens compared
      to histologically normal prostate tissue.
AB  - Benign prostatic hyperplasia (BPH) is linked to lower urinary tract symptoms
      (LUTS) such as incomplete bladder emptying, urinary frequency and urgency.
      Mechanisms responsible for BPH are not fully known. Here, we tested whether beta
      catenin (CTNNB1) immunostaining intensity and distribution differ in human
      glandular BPH tissue specimens compared to normal prostate tissue. Multiplex
      immunostaining of CTNNB1, its putative transcriptional target gene lymphoid
      enhancer binding factor 1 (LEF1), and the epithelial marker E-cadherin were
      examined in clinical human prostate specimens with or without histological BPH
      (pure epithelial or mixed stromal-epithelial nodules). BPH specimens were
      obtained from 24 men who experienced LUTS and underwent transurethral resection
      of the prostate surgery. Control specimens were tumor-adjacent histologically
      normal prostate tissue from 48 patients who underwent radical prostatectomy. The
      resulting multispectral images were unmixed and optical densities recorded to
      quantify staining abundance, cellular (membranous, cytoplasmic, and nuclear) and
      tissue localization (stromal versus epithelial), and determination of percentage
      of CTNNB1-positive cells. The following CTNNB1 indices were significantly higher
      in BPH compared to normal prostate tissue: overall staining intensity, staining
      intensity in prostate stromal cell membranes, cytoplasm and nuclei, and prostate
      epithelial cell nuclei. The following LEF1 indices were significantly lower in
      BPH compared to tumor-adjacent normal prostate tissue: stromal LEF1 staining
      intensity, percentage of LEF1-positive stromal cells, and intensity of LEF1
      staining in stromal cell membranes, cytoplasm, and nuclei. The percentage of
      stromal cells with CTNNB1(+)/LEF1(-) nuclei was higher and percentage of stromal
      cells with CTNNB1(-)/LEF1(+) nuclei was lower in BPH compared to tumor-adjacent
      normal prostate tissues. These results support the hypothesis that CTNNB1
      expression increases in specific BPH tissue compartments. Further, since nuclear
      LEF1 staining does not coincide with cytoplasmic or nuclear CTNNB1 staining, it
      does not appear to be a reliable index of CTNNB1 activity in adult human
      prostate. 

PMID- 25606579
TI  - The implications of prostate-specific antigen density to predict clinically
      significant prostate cancer in men <= 50 years.
AB  - To investigate the appropriate cut-off level of PSA or other clinical parameters
      at aged <= 50 years. The rate of detection of PCa in young men will continue to
      rise associated with the advancement of the current and evolving practices of
      screening and detection. In this study, we determined whether to investigate the
      appropriate cut-off level of PSA or other clinical parameters at aged <= 50
      years. The study population included 106 patients aged <= 50 years who had
      prostate biopsy at our institute. The differences of clinical variables including
      various PSA related parameters between the patients with significant PCa and
      insignificant PCa were analyzed. Receiver operating characteristics (ROC) curves
      and the corresponding areas under the ROC curves (AUC) were calculated. There
      were no significant differences between no-PCa and PCa patients regarding PSA
      value, prostate volume (P vol), PSA density (PSAD), transition zone volume (TZ
      vol), PSATZ density (PSATZD). When the patients meeting the following criteria,
      Gleason score was <= 6 with less than 2 positive biopsy cores, were classified as
      having insignificant prostate cancer, PSAD could become a useful predictor of
      significant PCa in men. The AUC was significantly greater in PSAD (0.801) than
      for the other parameters. The sensitivity and specificity of a PSAD threshold of
      0.32 were 85.7% and 77.8%, respectively. In conclusion, PSAD can be a useful and
      very effective predictor in a man aged <= 50 and we can counsel patients with
      discretion regarding the likelihood of significant PCa. 

PMID- 25606580
TI  - De novo large cell neuroendocrine carcinoma of the prostate, case report and
      literature review.
AB  - Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in
      particular, is an extremely rare entity that has only been described in the
      literature in case reports. Historically, the majority of the cases of LCNEC
      reported in the literature represent typical prostatic adenocarcinomas that
      transformed after long standing androgen deprivation therapy (ADT). These cases
      were admixed with histological areas of usual adenocarcinoma and showed hybrid
      features of both neuroendocrine and usual adenocarcinoma. Here we present a case
      of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de
      novo in a patient without prior history of hormonal therapy. The tumor also shows
      morphologic evidence of neuroendocrine differentiation; composed of large sheets
      and nests of cells with moderate amphophilic cytoplasm with peripheral
      palisading, and vesicular clumpy chromatin with prominent nucleoli. The
      carcinoma's prostatic origin is indicated by positive immunohistochemical
      staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining
      for chromogranin and synaptophysin, as well as the presence of secretory granules
      in the cytoplasm of the tumor cells demonstrated by electron microscopy supports
      the NE differentiation. NE prostate cancer usually does not express AR and is
      refractory to ADT therapy while AR and ERG are positive in this case. In summary,
      we report a de novo LCNEC of the prostate with review of literature, in
      particular, clinical implications. 

PMID- 25606582
TI  - Dental schools, medical centers, and research universities.

PMID- 25606581
TI  - Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the
      detection and management of prostate cancer.
AB  - Prostate-specific antigen (PSA) has been widely used as a serum marker for
      prostate cancer (PCa) screening or progression monitoring, which dramatically
      increased rate of early detection while significantly reduced PCa-specific
      mortality. However, a number of limitations of PSA have been noticed. Low
      specificity of PSA may lead to overtreatment in men who presenting with a total
      PSA (tPSA) level of < 10 ng/mL. As a type of free PSA (fPSA), [-2]proPSA is
      differentially expressed in peripheral zone of prostate gland and found to be
      elevated in serum of men with PCa. Two p2PSA-based derivatives, prostate health
      index (PHI) and %p2PSA, which were defined as [(p2PSA/fPSA) * ? tPSA] and
      [(p2PSA/fPSA) * 100] respectively, have been suggested to be increased in PCa and
      can better distinguish PCa from benign prostatic diseases than tPSA or fPSA. We
      performed a systematic review of the available scientific evidences to evaluate
      the potentials of %p2PSA and PHI in clinical application. Mounting evidences
      suggested that both %p2PSA and PHI possess higher area under the ROC curve (AUC)
      and better specificity at a high sensitivity for PCa detection when compare with
      tPSA and %fPSA. It indicated that measurements of %p2PSA and PHI significantly
      improved the accuracy of PCa detection and diminished unnecessary biopsies.
      Furthermore, elevations of %p2PSA and PHI are related to more aggressive
      diseases. %p2PSA and PHI might be helpful in reducing overtreatment on indolent
      cases or assessing the progression of PCa in men who undergo active surveillance.
      Further studies are needed before being applied in routine clinical practice. 

PMID- 25606583
TI  - Anterior all-ceramic superstructures: chance or risk?
AB  - The use of zirconia abutments for single-tooth restorations is well documented
      and supported by clinical studies with observational periods of up to 5 years.
      However, data for fixed partial dentures (FPDs) on all-ceramic abutments are
      lacking. Therefore, this indication cannot yet be generally recommended. Based on
      the available clinical studies, it can be assumed that the treatment results for
      anterior restorations can be improved by using all-ceramic abutments, especially
      in situations with a reduced thickness of the peri-implant soft tissues (< 2 mm).
      Zirconia abutments for single-tooth restorations can be restored with glass
      ceramic crowns on a lithium-disilicate base or crowns with oxide-ceramic
      structures (alumina or zirconia). If the restorations are cemented adhesively,
      then all of the cement residues must be carefully removed. Superstructures based
      on zirconia ceramics can be removed to a certain degree if they are cemented
      temporarily or screwfixed with directly veneered abutments. However, prior to
      providing a general recommendation for temporary cementation or screw-fixation of
      all-ceramic superstructures, additional clinical data are needed. 

PMID- 25606585
TI  - Plant science called up to provide food security.
AB  - The fundamental understanding of plant biochemistry, physiology and genetics,
      along with insights into ecology, plant evolution and the domestication of common
      crop species will have to serve agricultural applications to ensure that the
      growing population of our rapidly changing planet will have sufficient food in
      the coming decades. Michael Gross reports.

PMID- 25606584
TI  - Importance of determining indication for colonoscopy: implications for practice
      and policy original.

PMID- 25606586
TI  - Takashi Yoshimura.

PMID- 25606587
TI  - Cas proteins: dodgy scaffolding in breast cancer.
AB  - The members of the Cas protein family (p130Cas/BCAR1, Nedd9/HEF1, EFS and CASS4)
      are scaffold proteins required for the assembly of signal transduction complexes
      in response to several stimuli, such as growth factors, hormones and
      extracellular matrix components. Given their ability to integrate and coordinate
      multiple signalling events, Cas proteins have emerged as crucial players in the
      control of mammary cell proliferation, survival and differentiation. More
      importantly, it has been found that alterations of their expression levels result
      in aberrant signalling cascades, which promote initiation and progression of
      breast cancer. Based on the increasing data from in vitro, mouse model and
      clinical studies, in this review we will focus on two Cas proteins, p130Cas/BCAR1
      and Nedd9, and their coupled signalling pathways, to examine their role in
      mammary cell transformation and in the acquirement of invasiveness and drug
      resistance of breast cancer cells.

PMID- 25606589
TI  - Gout, tophi and the wonders of NETs.

PMID- 25606588
TI  - New concepts in breast cancer genomics and genetics.
AB  - Massively parallel DNA and RNA sequencing approaches have generated data on
      thousands of breast cancer genomes. In this review, we consider progress largely
      from the perspective of new concepts and hypotheses raised so far. These include
      challenges to the multistep model of breast carcinogenesis and the discovery of
      new defects in DNA repair through sequence analysis. Issues for functional
      genomics include the development of strategies to differentiate between mutations
      that are likely to drive carcinogenesis and bystander background mutations, as
      well as the importance of mechanistic studies that examine the role of mutations
      in genes with roles in splicing, histone methylation, and long non-coding RNA
      function. The application of genome-annotated patient-derived breast cancer
      xenografts as a potentially more reliable preclinical model is also discussed.
      Finally, we address the challenge of extracting medical value from genomic data.
      A weakness of many datasets is inadequate clinical annotation, which hampers the
      establishment of links between the mutation spectra and the efficacy of drugs or
      disease phenotypes. Tools such as dGene and the DGIdb are being developed to
      identify possible druggable mutations, but these programs are a work in progress
      since extensive molecular pharmacology is required to develop successful 'genome
      forward' clinical trials. Examples are emerging, however, including targeting
      HER2 in HER2 mutant breast cancer and mutant ESR1 in ESR1 endocrine refractory
      luminal-type breast cancer. Finally, the integration of DNA- and RNA-based
      sequencing studies with mass spectrometry-based peptide sequencing and an
      unbiased determination of post-translational modifications promises a more
      complete view of the biochemistry of breast cancer cells and points toward a new
      discovery horizon in our understanding of the pathophysiology of this complex
      disease.

PMID- 25606590
TI  - Clinical value of whole-body PET/CT in patients with active rheumatic diseases.
AB  - Advanced imaging techniques may enable early diagnosis and monitoring of therapy
      in various rheumatic diseases. To prevent irreversible tissue damage,
      inflammatory rheumatic disease must be diagnosed and treated in pre-clinical
      stages, requiring highly sensitive detection techniques. Positron emission
      tomography (PET) provides highly sensitive, quantitative imaging at a molecular
      level, revealing the important pathophysiological processes underlying
      inflammation. This review provides an overview of the current utility of 18 F
      fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active
      rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia
      rheumatica, adult-onset Still's disease, relapsing polychondritis, immunoglobulin
      G4-related disease, large-vessel vasculitis, Wegener's granulomatosis,
      polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the
      diagnosis and monitoring of these diseases.

PMID- 25606591
TI  - What has functional connectivity and chemical neuroimaging in fibromyalgia taught
      us about the mechanisms and management of 'centralized' pain?
AB  - Research suggests that fibromyalgia is a central, widespread pain syndrome
      supported by a generalized disturbance in central nervous system pain processing.
      Over the past decades, multiple lines of research have identified the locus for
      many functional, chronic pain disorders to the central nervous system, and the
      brain. In recent years, brain neuroimaging techniques have heralded a revolution
      in our understanding of chronic pain, as they have allowed researchers to non
      invasively (or minimally invasively) evaluate human patients suffering from
      various pain disorders. While many neuroimaging techniques have been developed,
      growing interest in two specific imaging modalities has led to significant
      contributions to chronic pain research. For instance, resting functional
      connectivity magnetic resonance imaging (fcMRI) is a recent adaptation of fMRI
      that examines intrinsic brain connectivity - defined as synchronous oscillations
      of the fMRI signal that occurs in the resting basal state. Proton magnetic
      resonance spectroscopy (1H-MRS) is a non-invasive magnetic resonance imaging
      technique that can quantify the concentration of multiple metabolites within the
      human brain. This review will outline recent applications of the complementary
      imaging techniques - fcMRI and 1H-MRS - to improve our understanding of
      fibromyalgia pathophysiology and how pharmacological and non-pharmacological
      therapies contribute to analgesia in these patients. A better understanding of
      the brain in chronic pain, with specific linkage as to which neural processes
      relate to spontaneous pain perception and hyperalgesia, will greatly improve our
      ability to develop novel therapeutics. Neuroimaging will play a growing role in
      the translational research approaches needed to make this a reality.

PMID- 25606592
TI  - Ubiquitin-specific proteases as therapeutic targets for the treatment of breast
      cancer.
AB  - Key mediators of signaling pathways in breast cancer involve post-translational
      protein modification, primarily mediated through phosphorylation and
      ubiquitination. While previous studies focused on phosphorylation events, more
      recent analysis suggests that ubiquitin plays a parallel and equally important
      role in several signaling and cell regulatory events in breast cancer.
      Availability of new tools capable of sensitive detection of gene mutations and
      aberrant expression of genes and proteins coupled with gene-specific knockdown
      and silencing protocols have provided insight into the previously unexplored
      ubiquitin regulatory process within these tumors. Ubiquitin-specific proteases
      are one class of enzymes with protein deubiquitinating activity, making up the
      majority of protein deubiquitinating diversity within mammalian cells. Ubiquitin
      specific proteases are also emerging as potential therapeutic targets in many
      diseases, including cancer. In this report, we summarize the involvement of this
      class of enzymes in breast cancer signaling and cell regulation and illustrate
      the potential for additional studies to define novel targets and approaches in
      breast cancer therapy.

PMID- 25606593
TI  - Current and emerging therapeutic strategies for preventing inflammation and
      aggrecanase-mediated cartilage destruction in arthritis.
AB  - Arthritis is a multifactorial disease for which current therapeutic intervention
      with high efficacy remains challenging. Arthritis predominately affects articular
      joints, and cartilage deterioration and inflammation are key characteristics.
      Current therapeutics targeting inflammatory responses often cause severe side
      effects in patients because of the systemic inhibition of cytokines or other
      global immunosuppressive activities. Furthermore, a lack of primary response or
      failure to sustain a response to treatment through acquired drug resistance is an
      ongoing concern. Nevertheless, treatments such as disease-modifying anti
      rheumatic drugs, biological agents, and corticosteroids have revealed promising
      outcomes by decreasing pain and inflammation in patients and in some cases
      reducing radiographic progression of the disease. Emerging and anecdotal
      therapeutics with anti-inflammatory activity, alongside specific inhibitors of
      the A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 repeats
      (ADAMTS) cartilage-degrading aggrecanases, provide promising additions to current
      arthritis treatment strategies. Thus, it is paramount that treatment strategies
      be optimized to increase efficacy, reduce debilitating side effects, and improve
      the quality of life of patients with arthritis. Here, we review the current
      strategies that attempt to slow or halt the progression of osteoarthritis and
      rheumatoid arthritis, providing an up-to-date summary of pharmaceutical treatment
      strategies and side effects. Importantly, we highlight their potential to
      indirectly regulate ADAMTS aggrecanase activity through their targeting of
      inflammatory mediators, thus providing insight into a mechanism by which they
      might inhibit cartilage destruction to slow or halt radiographic progression of
      the disease. We also contrast these with anecdotal or experimental administration
      of statins that could equally regulate ADAMTS aggrecanase activity and are
      available to arthritis sufferers worldwide. Finally, we review the current
      literature regarding the development of synthetic inhibitors directed toward the
      aggrecanases ADAMTS4 and ADAMTS5, a strategy that might directly inhibit
      cartilage destruction and restore joint function in both rheumatoid arthritis and
      osteoarthritis.

PMID- 25606594
TI  - beta1 and beta4 integrins: from breast development to clinical practice.
AB  - Following a highly dynamic and complex dialogue between the epithelium and the
      surrounding microenvironment, the mammary gland develops into a branching
      structure during puberty, buds during pregnancy, forms intricate polar acini
      during lactation and, once the babies are weaned, remodels and involutes. At
      every stage of menstrual and pregnancy cycles, interactions between the cells and
      the extracellular matrix (ECM) and homotypic and heterotypic cell-cell
      interactions give rise to the architecture and function of the gland at that
      junction. These orchestrated programs would not be possible without the important
      role of the ECM receptors, integrins being the prime examples. The ECM-integrin
      axis regulates many crucial cellular functions including survival, migration and
      quiescence; the imbalance in any of these processes could contribute to
      oncogenesis. In this review we spotlight the involvement of two prominent
      integrin subunits, beta1 and beta4 integrins, in cross-talk with tyrosine kinase
      receptors, and we discuss the roles of these integrin subunits in the biology of
      normal breast differentiation and as potential prognostic and therapeutic targets
      in breast cancer.

PMID- 25606595
TI  - Mesenchymal stem cells in the treatment of traumatic articular cartilage defects:
      a comprehensive review.
AB  - Articular cartilage has a limited capacity to repair following injury. Early
      intervention is required to prevent progression of focal traumatic chondral and
      osteochondral defects to advanced cartilage degeneration and osteoarthritis.
      Novel cell-based tissue engineering techniques have been proposed with the goal
      of resurfacing defects with bioengineered tissue that recapitulates the
      properties of hyaline cartilage and integrates into native tissue.
      Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given
      the high proliferative capacity of MSCs and their potential to differentiate into
      cartilage-producing cells - chondrocytes. MSCs are historically harvested through
      bone marrow aspiration, which does not require invasive surgical intervention or
      cartilage extraction from other sites as required by other cell-based strategies.
      Biomaterial matrices are commonly used in conjunction with MSCs to aid cell
      delivery and support chondrogenic differentiation, functional extracellular
      matrix formation and three-dimensional tissue development. A number of specific
      transplantation protocols have successfully resurfaced articular cartilage in
      animals and humans to date. In the clinical literature, MSC-seeded scaffolds have
      filled a majority of defects with integrated hyaline-like cartilage repair tissue
      based on arthroscopic, histologic and imaging assessment. Positive functional
      outcomes have been reported at 12 to 48 months post-implantation, but future work
      is required to assess long-term outcomes with respect to other treatment
      modalities. Despite relatively positive outcomes, further investigation is
      required to establish a consensus on techniques for treatment of chondral and
      osteochondral defects with respect to cell source, isolation and expansion,
      implantation density, in vitro precultivation, and scaffold composition. This
      will allow for further optimization of MSC proliferation, chondrogenic
      differentiation, bioengineered cartilage integration, and clinical outcome.

PMID- 25606597
TI  - Nociceptive neurons detect cytokines in arthritis.
AB  - Proinflammatory cytokines are major mediators in the pathogenesis of diseases of
      joints such as rheumatoid arthritis and osteoarthritis. This review emphasizes
      that proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1
      beta, interleukin-6 and interleukin-17 are also mediators of pain by directly
      acting on the nociceptive system. Proportions of nociceptive sensory neurons
      express receptors for these cytokines, and the application of cytokines rapidly
      changes the excitability, ion currents and second messenger systems of these
      neurons. By inducing persistent sensitization of nociceptive sensory neurons (C-
      and a proportion of Adelta-fibers) for mechanical stimuli in the joint (a process
      called peripheral sensitization), these cytokines significantly contribute to the
      persistent hyperalgesia typical for many disease states of the joint. In
      addition, the disease-associated release of cytokines in the spinal cord supports
      the generation of central sensitization. The therapeutic neutralization of
      proinflammatory cytokines thus not only reduces the process of inflammation but
      may directly reduce hyperalgesia and pain by reversing the neuronal effects of
      cytokines. It is emerging that different cytokines have different actions on
      neurons. The neutralization of tumor necrosis factor-alpha reduces both
      mechanical and thermal hyperalgesia of the joint. The neutralization of
      interleukin-1 beta attenuates thermal hyperalgesia whereas the neutralization of
      interleukin-6 and interleukin-17 mainly reduces mechanical hyperalgesia. These
      different effects are partly explained by influencing different target molecules
      in sensory neurons. For example, in cultured sensory neurons tumor necrosis
      factor-alpha and interleukin-1 beta upregulate the TRPV1 ion channel, which is
      involved in the transduction of heat stimuli, consistent with an effect of these
      cytokines in thermal hyperalgesia. By contrast, interleukin-17 upregulates the
      TRPV4 ion channel, which has a role in the transduction of mechanical stimuli.
      Thus, the analgesic potential of neutralizing cytokines seems to depend on which
      cytokine is mainly involved in the particular pain state.

PMID- 25606596
TI  - Immune checkpoint receptors in regulating immune reactivity in rheumatic disease.
AB  - Immune checkpoint regulators are critical modulators of the immune system,
      allowing the initiation of a productive immune response and preventing the onset
      of autoimmunity. Co-inhibitory and co-stimulatory immune checkpoint receptors are
      required for full T-cell activation and effector functions such as the production
      of cytokines. In autoimmune rheumatic diseases, impaired tolerance leads to the
      development of diseases such as rheumatoid arthritis, systemic lupus
      erythematosus, and Sjogren's syndrome. Targeting the pathways of the inhibitory
      immune checkpoint molecules CD152 (cytotoxic T lymphocyte antigen-4) and CD279
      (programmed death-1) in cancer shows robust anti-tumor responses and tumor
      regression. This observation suggests that, in autoimmune diseases, the converse
      strategy of engaging these molecules may alleviate inflammation owing to the
      success of abatacept (CD152-Ig) in rheumatoid arthritis patients. We review the
      preclinical and clinical developments in targeting immune checkpoint regulators
      in rheumatic disease.

PMID- 25606599
TI  - A scoring system for estimating the risk of advanced colorectal neoplasia at
      colonoscopy.

PMID- 25606600
TI  - Global mental health: development and collaboration.

PMID- 25606601
TI  - Response to 'OPN gene polymorphisms influence the risk of knee OA and OPN levels
      in synovial fluid in a Chinese population'.

PMID- 25606598
TI  - Regulatory T cells and control of the germinal centre response.
AB  - Germinal centres (GCs) are specialised lymphoid microenvironments that form in
      secondary B-cell follicles upon exposure to T-dependent antigens. In the GC,
      clonal expansion, selection and differentiation of GC B cells result in the
      production of high-affinity plasma cells and memory B cells that provide
      protection against subsequent infection. The GC is carefully regulated to fulfil
      its critical role in defence against infection and to ensure that immunological
      tolerance is not broken in the process. The GC response can be controlled by a
      number of mechanisms, one of which is by forkhead box p3 expressing regulatory T
      (Treg) cells, a suppressive population of CD4+ T cells. A specialised subset of
      Treg cells - follicular regulatory T (Tfr) cells - form after immunisation and
      are able to access the GC, where they control the size and output of the
      response. Our knowledge of Treg cell control of the GC is expanding. In this
      review we will discuss recent advances in the field, with a particular emphasis
      on the differentiation and function of Tfr cells in the GC.

PMID- 25606602
TI  - Influence of temperature and fat content on ideal sucrose concentration,
      sweetening power, and sweetness equivalence of different sweeteners in chocolate
      milk beverage.
AB  - The introduction of new products catering to specific dietary needs and the
      corresponding changes in the consumer profile reflect a growing demand for diet
      and "light" products. However, little information is available regarding the
      sensory effects of different sweeteners in products consumed at different
      temperatures and with varying fat contents. In this regard, this study aimed to
      determine the influence of temperature and fat content on the ideal sucrose
      concentration and the sweetness equivalence and sweetening power of different
      sweeteners: Neotame (NutraSweet Corp., Chicago, IL), aspartame, neosucralose,
      sucralose, and stevia (95% rebaudioside A), with sucrose as reference, in a
      chocolate milk beverage using a just-about-right (JAR) scale and magnitude
      estimation. Increasing temperature of consumption had an inverse effect on the
      ideal sucrose concentration in whole milk beverages, whereas no difference was
      noted in beverages made skim milk. In addition, a decrease in sweetening power
      was observed for all of the sweeteners analyzed considering the same conditions.
      The findings suggest that different optimal conditions exist for consumption of
      chocolate milk beverage related to sweetness perception, which depends on the fat
      level of milk used in the formulation. This information can be used by
      researchers and dairy processors when developing chocolate milk beverage
      formulations.

PMID- 25606603
TI  - Minimum risk and HEAT-PPCI: innovative ideas for informed consent in emergency
      medical research.

PMID- 25606604
TI  - An empty toolbox: hydrocodone to schedule II.

PMID- 25606605
TI  - Investigation of the use and feasibility of speed warning systems.

PMID- 25606606
TI  - Removal notice to "Protective effect of Daucus carota against UV-DMBA induced
      skin cancer in mice" [Chem. Biol. Interact. 219 (2014) 48-56].

PMID- 25606607
TI  - Britain on brink of freshwater species invasion from south east  Europe.

PMID- 25606608
TI  - Pipeline to replenish vanishing Dead Sea.

PMID- 25606609
TI  - Law of the Sea authorizes animal tagging research without nations' consent.

PMID- 25606610
TI  - Top marine scientists call for action on 'invisible' fisheries.

PMID- 25606611
TI  - Seismic network will measure the effects of ocean waves on  Antarctic ice
      shelves.

PMID- 25606612
TI  - Emerging disease in Europe could wipe out American  salamanders.

PMID- 25606613
TI  - Past climate change was caused by the ocean, not just the  atmosphere.

PMID- 25606614
TI  - Pharmaceuticals and the water-fish-osprey food web.

PMID- 25606615
TI  - Rescued penguin chicks survival similar to colony rates.

PMID- 25606616
TI  - Antarctic scientists create 'future ocean'.

PMID- 25606617
TI  - Northwestern Hawaiian Islands clean up.

PMID- 25606618
TI  - Restoring wetlands can lessen soil sinkage.

PMID- 25606619
TI  - California mussels contaminated with Giardia.

PMID- 25606620
TI  - Inexpensive simulator for studying tidal marsh plants.

PMID- 25606621
TI  - Advancing the boundaries of molecular cellular pathology.

PMID- 25606622
TI  - Elie Sanchez, 1944-2014.

PMID- 25606623
TI  - New graduate nurses in transition: a review of transition programmes and
      transition experiences within mental health care.
AB  - Research on experiences of transition into mental health-care roles seems sparse,
      but it is vital in order to produce a comprehensive understanding of the
      transition into mental health-care roles and to serve as a foundation for future
      research and development. The aim of the present study was to review existing
      research literature, and in doing so, investigate transition programmes for new
      graduate nurses (NGN) into mental health care, and their experiences of role
      transition and evaluations of participation in transition programmes. The
      literature review spans literature published after the year 2000. The literature
      search was conducted using the following databases: CINAHL, Psychology and
      Behavioral Sciences Collection, PsycINFO, and Pubmed. Search results consisting
      of 14 articles were analysed using thematic analysis. Results from the analysis
      showed four overall themes: nursing education, transition programmes and
      evaluations, working environment, and the NGN role. We conclude that it is not
      possible to produce a comprehensive understanding specifically concerning the
      transition programmes for NGN into mental health care, and that further research
      is necessary due to the limitations of this review.

PMID- 25606624
TI  - An innovative approach to enhancing continuing education   activities for
      practising pharmacists using clicker technology.
AB  - OBJECTIVE: The objective of this study was to evaluate the use of an audience
      response system (i.e. clickers) as an engaging tool for learning and examine its
      potential for enhancing continuing education (CE) activities. METHODS: Attendees
      at a symposium were invited to utilise and evaluate the use of clickers.
      Electronic data relating to participant demographics and feedback were collected
      using clickers during the symposium. RESULTS: The 60 attendees who used the
      clickers were mostly pharmacists (76%) who worked in hospital pharmacy practice
      (86%). Attendees strongly agreed or agreed that clickers were easy to use (94%),
      enhanced interaction (98%), allowed comparison of knowledge with that of their
      peers (78%), brought to attention their knowledge deficits (64%) and should be
      used again (94%). CONCLUSION: The innovative use of clickers at the symposium was
      very well received by all attendees and offered a number of benefits, including
      the ability to provide a more engaging and interactive CE activity.

PMID- 25606625
TI  - Editorial: introduction to special issue on aging families.

PMID- 25606626
TI  - In vitro platelets in sight.

PMID- 25606627
TI  - Unexplained bleeding: another player to look out for!

PMID- 25606628
TI  - Oral anticoagulants: new and improved.

PMID- 25606629
TI  - Bringing out the DCs' softer side in GVHD.

PMID- 25606630
TI  - In utero transplantation may soon be in delivery.

PMID- 25606632
TI  - Challenges in nutrition support. Editor's note.

PMID- 25606631
TI  - Platelet bioreactor-on-a-chip.
AB  - Platelet transfusions total >2.17 million apheresis-equivalent units per year in
      the United States and are derived entirely from human donors, despite clinically
      significant immunogenicity, associated risk of sepsis, and inventory shortages
      due to high demand and 5-day shelf life. To take advantage of known physiological
      drivers of thrombopoiesis, we have developed a microfluidic human platelet
      bioreactor that recapitulates bone marrow stiffness, extracellular matrix
      composition,micro-channel size, hemodynamic vascular shear stress, and
      endothelial cell contacts, and it supports high-resolution live-cell microscopy
      and quantification of platelet production. Physiological shear stresses triggered
      proplatelet initiation, reproduced ex vivo bone marrow proplatelet production,
      and generated functional platelets. Modeling human bone marrow composition and
      hemodynamics in vitro obviates risks associated with platelet procurement and
      storage to help meet growing transfusion needs.

PMID- 25606633
TI  - Hurricane Sandy nutrition support during disasters.
AB  - Natural disasters and weather-related emergencies can strike at a moment's
      notice. Individuals with chronic health conditions and other special needs are
      especially vulnerable. Basic services such as water, electricity, gas, and
      telephone service may not be available. Home parenteral and enteral nutrition
      consumers are at a serious risk as they depend on clean water and power for
      nutrient delivery. Creating a comprehensive emergency preparedness plan is
      imperative for both the home parenteral and enteral consumer and home care
      provider to ensure that special needs are met. Home care providers can assist
      home parenteral and enteral consumers in disaster and emergency planning.

PMID- 25606634
TI  - Nutrition in the Great East Japan Earthquake Disaster.
AB  - The Great East Japan Earthquake Disaster (GEJED) struck the northeast region of
      Honshu, the main island of Japan, on March 11, 2011. This mega-disaster claimed
      more than 15,000 lives, with approximately 3000 later deaths being disaster
      related. The GEJED consisted of a mega-earthquake, tsunami, and nuclear accident.
      Survivors living in temporary shelters might have received insufficient levels of
      vitamins, with the exception of vitamin B1, which appeared to be overestimated,
      and excess levels of sodium. However, scientific data collection and surveys
      following the GEJED were extremely limited. This experience highlights the need
      to prepare an "emergency nutrition assessment" system for optimal nutrition in
      future disasters.

PMID- 25606635
TI  - Once upon a storm: Katrina and nutrition support or the lack thereof.
AB  - Nutrition support teams face many challenges to establish, fund, maintain, and
      justify their existence. Some of the challenges can be resolved over time.
      However, the challenge of providing nutrition in general and nutrition support in
      specific during a natural disaster is void of the luxury of time experienced with
      the previously delineated challenges. The experience of Methodist Hospital in New
      Orleans, Louisiana, during Hurricane Katrina in 2005 in providing nutrition and
      nutrition support is summarized in this invited article. The recollections of
      various represented disciplines are bolstered by tables and figures that outline
      the 7 days before and after Katrina. Transdisciplinarity was exhibited through
      the performance of nontraditional functions or tasks by a variety of
      professionals who lived 5 days or longer in the "Methodist Island." Lessons
      learned and considerations for disaster preparedness as it relates to nutrition
      and nutrition support as well as general considerations are provided.

PMID- 25606636
TI  - Provision of nutrition support therapies in the recent Iraq and Afghanistan
      conflicts.
AB  - This article describes the experience of nutrition support practitioners,
      specifically dietitians, providing care to combat casualties. It provides a brief
      overview of dietitians' induction into armed service but focuses primarily on
      their role in providing nutrition support during the most recent conflicts in
      Iraq and Afghanistan. The current system of combat casualty care is discussed
      with specific emphasis on providing early and adequate nutrition support to U.S.
      combat casualties from injury, care in theater combat support hospitals
      (CSHs)/expeditionary medical support (EMEDs), and en route care during critical
      care air transport (CCAT) up to arrival at treatment facilities in the United
      States. The article also examines practices and challenges faced in the
      CSHs/EMEDs providing nutrition support to non-U.S. or coalition patients. Over
      the past decade in armed conflicts, dietitians, physicians, nurses, and other
      medical professionals have risen to challenges, have implemented systems, and
      continue working to optimize treatment across the spectrum of combat casualty
      care.

PMID- 25606637
TI  - Leadless pacing debate: current issues in pacing.

PMID- 25606638
TI  - Tackling heart failure in Africa via innovative research: setting the agenda.

PMID- 25606639
TI  - European interventionists leading treatment of valvular heart disease.

PMID- 25606640
TI  - The 'Ten commandments' for European Society   of Cardiology guidelines on aortic
      diseases.

PMID- 25606641
TI  - Prof. Raimund Erbel and Prof. Victor Aboyans   discuss the 2014 European Society
      of Cardiology   guidelines on the diagnosis and treatment of aortic   diseases
      with Emma Wilkinson.

PMID- 25606642
TI  - New enteral connectors raising awareness.
AB  - Small-bore connectors, in the past, have enabled misconnections between
      therapeutic systems that should not connect. Many enteral misconnections have
      been reported with subsequent frequent fatal outcomes. New enteral connectors
      have been designed via an International Organization of Standardization (ISO)
      standards development process. The new patient access connectors will be in the
      marketplace soon for the purpose of improving patient safety. Becoming aware of
      the changes and planning for them within your facility or agency will ease the
      transition to these new devices while continuing enteral nutrition support.
      Clinicians should look for education and information from appropriate resources
      and work with their suppliers to see when these changes will come to their
      institution or agency.

PMID- 25606643
TI  - Nutrition and small bowel transplantation.
AB  - Intestinal transplantation is indicated for patients with intractable intestinal
      failure, especially when life-threatening complications of parenteral nutrition
      (PN) occur. The rates of 1- and 5-year graft survival range from 65%-80% and 40%
      50% across differing age ranges, with adult recipients generally performing
      better. Despite nutrition being so central to intestinal transplantation, there
      are little published literature and essentially no data from clinical trials. In
      this review, we critically examine published manuscripts in an attempt to draw
      common themes between various transplant programs, covering experimental
      physiologic data, published nutrition protocols, and common postoperative
      management issues. We conclude that the well-established intestinal graft in a
      healthy state absorbs key nutrients adequately to wean off PN and that the wide
      variation in practice across different programs suggests that different
      approaches can equally lead to success.

PMID- 25606644
TI  - Nutrition and anabolic pharmacotherapies in the care of burn patients.
AB  - Thermal injury is a devastating injury that results in a number of pathological
      alterations in almost every system in the body. Hypermetabolism, muscle wasting,
      depressed immunity, and impaired wound healing are all clinical features of
      burns. Failure to address each of these specific pathological alterations can
      lead to increased mortality. Nutrition supplementation has been recommended as a
      therapeutic tool to help attenuate the hypermetabolism and devastating catabolism
      evident following burn. Despite the wide consensus on the need of nutrition
      supplementation in burn patients, controversy exists with regard to the type and
      amount of nutrition recommended. Nutrition alone is also not enough in these
      patients to halt and reverse some of the damage done by the catabolic pathways
      activated following severe burn injury. This has led to the use of anabolic
      pharmacologic agents in conjunction with nutrition to help improve patient
      outcome following burn injury. In this review, we examine the relevant literature
      on nutrition after burn injury and its contribution to the attenuation of the
      postburn hypermetabolic response, impaired wound healing, and suppressed
      immunological responses. We also review the commonly used anabolic agents
      clinically in the care of burn patients. Finally, we provide nutrition and
      pharmacological recommendations gained from prospective trials, retrospective
      analyses, and expert opinions based on our practice at the Ross Tilley Burn
      Center in Toronto, Canada.

PMID- 25606645
TI  - 3-in-1 vs 2-in-1 parenteral nutrition in adults: a review.
AB  - Parenteral nutrition (PN) provides a means of nourishment for patients in whom
      oral or enteral nutrition is not possible or practical. Initial formulations
      consisted of carbohydrates (dextrose), amino acids, vitamins, trace minerals,
      electrolytes, and water. A stable intravenous fat emulsion (IVFE) permitted the
      combination of all 3 macronutrients in the same admixture (3-in-1 or total
      nutrient admixture [TNA]). Many institutions have adopted these TNAs as the
      standard formulation. Others, due to a variety of concerns (including historical
      concerns regarding stability), continue to administer PN as a formulation of
      dextrose and amino acids (2-in-1) with separate IVFE infusions. The aim of this
      article is to review the literature regarding the use of TNA vs 2-in-1
      formulations. The published data were critically analyzed, and a preferred
      strategy was suggested based on an interpretation of the data. Concerns
      surrounding the safety of 2-in-1 vs 3-in-1 PN formulations can be grouped with
      respect to those regarding infections, emulsion instability ("cracking"), and
      precipitant formation. These concerns are largely historical and would seem to be
      no longer relevant to adult PN formulations. We believe that the available
      (limited) data support the safe transition to the 3-in-1 formulation as the
      standard of care in adult PN.

PMID- 25606646
TI  - Implementation of a dietitian-led enteral nutrition support clinic results in
      quality improvement, reduced readmissions, and cost savings.
AB  - BACKGROUND: Enteral access device malfunction and breakage results in significant
      morbidity and healthcare cost. In many healthcare systems, enteral nutrition care
      is fragmented and inefficient. We describe the development and validation of an
      enteral nutrition support clinic (NSC) with a focus on prevention of enteral
      access complications. A care protocol consisting of pre- and postplacement visits
      and subsequent weekly visits was developed. Competencies were established for
      dietitians to staff the NSC. METHODS: A retrospective quality analysis was
      performed in patients before and after the implementation of an enteral NSC.
      Enteral access complications, emergency room visits, readmissions, unplanned
      physician visits, and tube replacements were recorded for 90 days after tube
      placement. RESULTS: Thirty patients were evaluated in the NSC pilot and compared
      with 22 baseline patients with adequate follow-up. The NSC resulted in an 88.9%
      reduction in nutrition-related emergency room visits (P = .016) and 78.1%
      reduction in readmissions (P = .027). Estimated per-patient cost reductions
      amounted to $6831. Approximately 30% of patients were seen in the NSC at least
      once for a clogged tube and 43.3% for tube leakage. Only 1 NSC patient required a
      procedure for tube reinsertion. CONCLUSION: Implementation of a dietitian-led
      nutrition support clinic resulted in improved quality, as well as reductions in
      hospital readmissions, tube-related complications, and healthcare costs

PMID- 25606647
TI  - Delivered volumes of enteral nutrition exceed prescribed volumes.
AB  - BACKGROUND: Enteral nutrition (EN) provisions are typically calculated based on a
      24-hour infusion period. However, feedings are often interrupted for daily
      activities, procedures, or gastrointestinal intolerance. The study's objective
      was to determine the delivered EN quantities provided to stable hospitalized
      patients, using cellular time and measured volumes to verify our EN calculation
      adjustment. METHODS: A supply of consecutively numbered ready-to-hang (RTH) EN
      product was delivered to the bedside of 26 inpatients with established EN
      tolerance at goal rates on various types of nursing units. The dietitian weighed
      the volume remaining in the infusing product and recorded the measurement time.
      On the following days, the dietitian continued to weigh the infusing RTH product
      and the empty RTH bottles saved by nursing. The primary outcome was the
      difference between the prescribed and delivered EN provisions, which was
      calculated with a paired t test. RESULTS: Patients received significantly more
      calories in the delivered enteral feeding (mean [SD], 1678 [385] kcal) than
      prescribed calories in the EN order (1489 [246 kcal]; t = 3.736, P = .001),
      adjusting for observed time. No significant differences were found between
      nursing units, product, and rate. CONCLUSION: EN delivered may actually exceed
      ordered amounts by 5%-21% (mean, 12%) with feeding pump inaccuracy as the primary
      contributing factor. This differs from what others have found. Our findings
      support using a volume-based ordering system vs a rate-based ordering system for
      more accurate EN delivery.

PMID- 25606648
TI  - Nasal bridles for securing nasoenteric tubes: a meta-analysis.
AB  - BACKGROUND: Nasoenteric feeding tubes may easily become dislodged due to patient
      mental status, transfers, or positional changes. Nasal bridles were introduced to
      provide a better, more reliable system to secure these tubes. This meta-analysis
      was performed to evaluate the effectiveness of nasal bridles compared with the
      traditional method of adhesive tape alone in securing enteral feeding tubes.
      MATERIALS AND METHODS: Multiple databases were searched (October 2013). All
      studies that evaluated the use of nasal bridles in adult patients were included
      in the analysis. Meta-analysis for the outcomes from use of a nasal bridle vs the
      more traditional method of adhesive tape alone for securing nasoenteric tubes was
      analyzed by calculating pooled estimates of dislodgement, skin complications, and
      sinusitis. Statistical analysis was performed using RevMan 5.1. RESULTS: Six
      studies (n = 594) met the inclusion criteria. Use of a nasal bridle for securing
      enteral tubes resulted in a statistically significant reduction in tube
      dislodgement compared with traditional adhesive tape alone (odds ratio [OR],
      0.16; 95% confidence interval [CI], 0.10-0.27; P < .01). The use of nasal bridles
      was associated with a higher rate of skin complications compared with traditional
      adhesive tape (OR, 4.27; 95% CI, 1.79-10.23; P < .01). Incidence of sinusitis was
      no different between the 2 groups (OR, 0.26; 95% CI, 0.03-2.28; P = .22).
      CONCLUSION: Nasal bridles appear to be more effective at securing nasoenteric
      tubes and preventing dislodgement than traditional use of tape alone.

PMID- 25606649
TI  - Uveal melanoma with diffuse bone marrow involvement.

PMID- 25606650
TI  - Functional hyposplenism diagnosed by blood film examination.

PMID- 25606654
TI  - [Fewer cases of decompression sickness in Vastra Gotaland. Eight years of
      statistics show a reduced number of consultations and treatments].
AB  - During the period 2005 to 2012, a total of 340 consultations (phone calls and/or
      visits) regarding possible decompression illness were recorded at the two
      hospitals with recompression chambers in the Vastra Gotaland region, Sweden. An
      analysis of the data showed a trend towards fewer consultations and recompression
      treatments. A similar trend has been observed in many other countries. Possible
      reasons for this reduction in the number of cases are discussed. Most of the
      patients only present relatively mild signs and symptoms at the time of
      consultation. This, together with the fact that the number of patients is low,
      involves a risk that awareness and knowledge regarding correct handling and care
      in diving accidents might be lost. Since rapid and correct care of decompression
      illness is important to avoid later sequeale it is important that competence in
      diving medicine is maintained at hospitals Nationwide.

PMID- 25606655
TI  - [Numerous hypotheses about sudden infant death ... but no impact].

PMID- 25606656
TI  - [Iron intoxication--poisoning with easily accessible medicines].
AB  - A 20-year-old woman was found semiconscious on the floor in a pool of black
      diarrhea with an empty 100 jar of ferrous sulphate beside her (100 mg
      Fe2+/tablet), 160 mg/kg. She was brought to the hospital an estimated 4 hours
      after ingestion and presented with irritability and a fluctuating CNS depression.
      Her blood pressure was 190/85 mmHg and pulse 130 bpm. An arterial blood gas
      analysis showed pH 7.17, pCO2 5.4 kPa, pO2 16.7 kPa and BE -14 mmol/l.
      Deferoxamine was started immediately with a dose of 15 mg/kg/h intravenously. The
      patient was intubated in the ICU and whole bowel irrigation was performed. Due to
      technical problems with the venous blood sampling, a correct measurement of the
      serum iron concentration (s-Fe2) was not at hand until 15 hours post ingestion
      and showed 131 umol/l. At that point her condition deteriorated with circulatory
      instability, hepatic failure, coagulopathy and renal insufficiency. Despite full
      treatment including continuous renal replacement therapy she died after 4 Days.

PMID- 25606657
TI  - [Most musculoskeletal soft tissue tumors are benign].
AB  - Most musculoskeletal soft tissue tumors are benign, lipoma being the most common.
      Malignant soft tissue tumors may be difficult to clinically distinguish from
      benign. Scandinavian recommendations are that all lesions suspicious for sarcoma
      be referred to a sarcoma center. This has led to improved tumor control and less
      post-operative functional deficits. Magnetic resonance imaging (MRI) can reliably
      diagnose lipomas, and further work-up is not necessary. Lipomas can be treated at
      the local hospital. All deep seated musculoskeletal tumors (under the muscle
      fascia) not unequivocally lipomas should be referred to a sarcoma center. All
      superficial (subcutaneous) musculoskeletal tumors larger than 5 cm and not
      unequivocally lipomas should be referred to a sarcoma center.

PMID- 25606658
TI  - [2.0 and health care--partly right, but just as often wrong].

PMID- 25606659
TI  - [Criticism without evidence, symptomatic of the health care debate].

PMID- 25606660
TI  - [Hormone replacement therapy in menopause--risk of disreputable activities].

PMID- 25606661
TI  - [Pain as source of joy--and necessary evil].

PMID- 25606662
TI  - Toward selection of efficient density functionals for van der Waals molecular
      complexes: comparative study of C-H...pi and N-H...pi interactions.
AB  - We have evaluated the performance of two of the recently developed density
      functionals (M06-2X and B2PLYP-D), which are widely used, by considering three
      important prototype systems, including benzene-acetylene, benzene-methane, and
      benzene-ammonia, possessing C-H...pi or N-H...pi interactions. Computational
      results are compared with the available experimental data. Considered density
      functionals are from two different classes: hybrid meta density functional (M06
      2X) and double hybrid density functional (B2PLYP-D). The performance of a range
      of basis sets (6-31G(d), 6-31+G(d), 6-31+G(d,p), 6-311G(d,p), 6-311+G(d,p), aug
      cc-pVXZ (X = D, T, Q)) with the above-mentioned two density functionals was
      evaluated. Comparison of the results includes Pople's basis sets versus Dunning's
      correlation consistent basis sets with the M06-2X and B2PLYP-D functionals
      considered in this study. The basis set effect on geometrical parameters,
      dissociation energies, and selected vibrational frequency shifts was thoroughly
      analyzed. We have addressed whether the counterpoise corrections with geometry
      optimizations and vibrational frequencies are important. Our computational study
      reveals that calculations carried out with smaller basis sets very well reproduce
      the reported experimental values of dissociation energies. The present study also
      shows that using the very large Dunning's correlation consistent basis set
      worsens the results. The necessity of including counterpoise correction for
      binding energies depends on the system and the type of method used. In general,
      vibrational frequency calculations using these DFT functionals generate
      characteristic red shifts for the C-H...pi or N-H...pi interactions in the
      complexes. 

PMID- 25606663
TI  - Single gold@silver nanoprobes for real-time tracing the entire autophagy process
      at single-cell level.
AB  - This article describes a multimodified core-shell gold@silver nanoprobe for real
      time monitoring the entire autophagy process at single-cell level. Autophagy is
      vital for understanding the mechanisms of human pathologies, developing novel
      drugs, and exploring approaches for autophagy controlling. A major challenge for
      autophagy study lies in real-time monitoring. One solution might come from real
      time detection of in situ superoxide radicals (O2(*-)), because it is the main
      regulator of autophagy. In this work, our proposed nanoprobes were etched by O2(*
      ) and gave a notable wavelength change in the plasmon resonance scattering
      spectra. Both the experimental and simulated results suggested the wavelength
      change rate correlated well with O2(*-) level. This response enabled its
      application in real-time in situ quantification of O2(*-) during autophagy
      course. More importantly, with the introduction of "relay probe" operation, two
      types of O2(*-)-regulating autophagy processes were successfully traced from the
      beginning to the end, and the possible mechanism was also proposed. 

PMID- 25606664
TI  - Molecular basis for antagonistic activity of anifrolumab, an anti-interferon
      alpha receptor 1 antibody.
AB  - Anifrolumab (anifrolumab) is an antagonist human monoclonal antibody that targets
      interferon alpha receptor 1 (IFNAR1). Anifrolumab has been developed to treat
      autoimmune diseases and is currently in clinical trials. To decipher the
      molecular basis of its mechanism of action, we engaged in multiple epitope
      mapping approaches to determine how it interacts with IFNAR1 and antagonizes the
      receptor. We identified the epitope of anifrolumab using enzymatic fragmentation,
      phage-peptide library panning and mutagenesis approaches. Our studies revealed
      that anifrolumab recognizes the SD3 subdomain of IFNAR1 with the critical residue
      R(279). Further, we solved the crystal structure of anifrolumab Fab to a
      resolution of 2.3 A. Guided by our epitope mapping studies, we then used in
      silico protein docking of the anifrolumab Fab crystal structure to IFNAR1 and
      characterized the corresponding mode of binding. We find that anifrolumab
      sterically inhibits the binding of IFN ligands to IFNAR1, thus blocking the
      formation of the ternary IFN/IFNAR1/IFNAR2 signaling complex. This report
      provides the molecular basis for the mechanism of action of anifrolumab and may
      provide insights toward designing antibody therapies against IFNAR1. 

PMID- 25606666
TI  - The incidence of giant cell arteritis in Olmsted County, Minnesota, over a 60
      year period 1950-2009.
AB  - OBJECTIVE: To assess the incidence of giant cell arteritis (GCA) in the era from
      2000 to 2009. METHOD: We extended the previously identified population-based
      cohort of Olmsted County, Minnesota residents who fulfilled 1990 American College
      of Rheumatology (ACR) criteria for GCA for earlier decades during 1950-1999.
      RESULTS: In 2000-2009, 74 cases of GCA were identified (mean age 78.1 years; 80%
      women; 79% temporal artery biopsy positive; seven included based on radiological
      criteria). The incidence of GCA was 19.8 per 100,000 population. CONCLUSIONS: The
      GCA incidence rates have remained steady since 1970 and the age at incidence,
      which was progressively increasing, seems to have reached a plateau.

PMID- 25606665
TI  - Screening of cell cycle fusion proteins to identify kinase signaling networks.
AB  - Kinase signaling networks are well-established mediators of cell cycle
      transitions. However, how kinases interact with the ubiquitin proteasome system
      (UPS) to elicit protein turnover is not fully understood. We sought a means of
      identifying kinase-substrate interactions to better understand signaling pathways
      controlling protein degradation. Our prior studies used a luciferase fusion
      protein to uncover kinase networks controlling protein turnover. In this study,
      we utilized a similar approach to identify pathways controlling the cell cycle
      protein p27(Kip1). We generated a p27(Kip1)-luciferase fusion and expressed it in
      cells incubated with compounds from a library of pharmacologically active
      compounds. We then compared the relative effects of the compounds on p27(Kip1)
      luciferase fusion stabilization. This was combined with in silico kinome
      profiling to identify potential kinases inhibited by each compound. This approach
      effectively uncovered known kinases regulating p27(Kip1) turnover. Collectively,
      our studies suggest that this parallel screening approach is robust and can be
      applied to fully understand kinase-ubiquitin pathway interactions. 

PMID- 25606667
TI  - Tetracycline-loaded biomimetic apatite: an adsorption study.
AB  - Biomimetic apatites are appealing compounds for the elaboration of bioactive bone
      repair scaffolds due to their intrinsic similarity to bone mineral. Bone
      surgeries are however often heavy procedures, and the infiltration of pathogens
      may not be totally avoided. To prevent their development, systemic antibiotic
      prophylaxis is widespread but does not specifically target surgical sites and
      involves doses not always optimized. A relevant alternative is a preliminary
      functionalization by an infection-fighting agent. In this work, we investigated
      from a physicochemical viewpoint the association of a wide-spectrum antibiotic,
      tetracycline (TC), and a biomimetic nanocrystalline apatite previously
      characterized. TC adsorption kinetics and isotherm were thoroughly explored.
      Kinetic data were fitted to various models (pseudo-first-order, pseudo-second
      order, general kinetic model of order n, Elovich, double-exponential, and purely
      diffusive models). The best fit was found for a double-exponential kinetic model
      or with a decimal reaction order of 1.4, highlighting a complex process with such
      TC molecules which do not expose high-affinity end groups for the surface of
      apatite. The adsorption isotherm was perfectly fitted to the Sips (Langmuir
      Freundlich) model, while other models failed to describe it, and the Sips
      exponent greater than unity (1.08) suggested a joint impact of surface
      heterogeneity and positive cooperativity between adsorbed molecules. Finally,
      preliminary insights on TC release from pelletized nanocrystalline apatite, in
      aqueous medium and neutral pH, were obtained using a recirculation cell,
      indicating a release profile mainly following a Higuchi-like diffusion-limited
      rate. This work is intended to shed more light on the interaction between polar
      molecules not exhibiting high-affinity end groups and biomimetic apatites and is
      a starting point in view of the elaboration of biomimetic apatite-based bone
      scaffolds functionalized with polar organic drugs for a local delivery. 

PMID- 25606668
TI  - Do genes modify the association of selenium and lipid levels?
AB  - The interaction of selenium, a component of antioxidant selenoproteins, with
      genetic variation in lipid-related pathways has not been evaluated earlier as a
      potential determinant of blood lipid levels. We aimed at evaluating the effects
      of gene-environment interactions between plasma levels of selenium and
      polymorphisms in lipid metabolic pathways on plasma lipid levels in a study
      population from Spain (N=1,315). We observed statistically significant
      associations between plasma selenium and lipid levels (differences in total, low
      density lipoprotein [LDL]-cholesterol, and triglycerides comparing the 80th with
      the 20th percentiles of plasma selenium levels were, respectively, 12.0 (95%
      confidence interval 6.3, 17.8), 8.9 (3.7, 14.2), and 9.0 (2.9, 15.2) mg/dl). We
      also found statistically significant interactions at the Bonferroni-corrected
      significance level (p=0.0008) between selenium and rs2290201 in FABP4 for total
      and LDL cholesterol levels and rs1800774 in CETP for elevated LDL cholesterol.
      Other polymorphisms showed statistically significant differential associations of
      plasma selenium levels and lipids biomarkers at the nominal p-value of 0.05.
      Reported statistical interactions with genes involved in lipid transport and
      transfer provide biological support to the positive associations of selenium with
      lipids shown in cross-sectional studies and lead to the hypothesis that selenium
      and lipid levels share common biological pathways that need to be elucidated in
      mechanistic studies.

PMID- 25606669
TI  - A stochastic relationship.

PMID- 25606670
TI  - Beating the millisecond barrier in molecular dynamics simulations.

PMID- 25606671
TI  - Local perturbation analysis: a computational tool for biophysical reaction
      diffusion models.
AB  - Diffusion and interaction of molecular regulators in cells is often modeled using
      reaction-diffusion partial differential equations. Analysis of such models and
      exploration of their parameter space is challenging, particularly for systems of
      high dimensionality. Here, we present a relatively simple and straightforward
      analysis, the local perturbation analysis, that reveals how parameter variations
      affect model behavior. This computational tool, which greatly aids exploration of
      the behavior of a model, exploits a structural feature common to many cellular
      regulatory systems: regulators are typically either bound to a membrane or freely
      diffusing in the interior of the cell. Using well-documented, readily available
      bifurcation software, the local perturbation analysis tracks the approximate
      early evolution of an arbitrarily large perturbation of a homogeneous steady
      state. In doing so, it provides a bifurcation diagram that concisely describes
      various regimes of the model's behavior, reducing the need for exhaustive
      simulations to explore parameter space. We explain the method and provide
      detailed step-by-step guides to its use and application.

PMID- 25606673
TI  - Cell Volume Fluctuations in MDCK Monolayers.
AB  - Cells moving collectively in tissues constitute a form of active matter, in which
      collective motion depends strongly on driven fluctuations at the single-cell
      scale. Fluctuations in cell area and number density are often seen in monolayers,
      yet their role in collective migration is not known. Here we study density
      fluctuations at the single- and multicell level, finding that single-cell volumes
      oscillate with a timescale of 4 h and an amplitude of 20%; the timescale and
      amplitude are found to depend on cytoskeletal activity. At the multicellular
      scale, density fluctuations violate the central limit theorem, highlighting the
      role of nonequilibrium driving forces in multicellular density fluctuations.

PMID- 25606672
TI  - Molecular biophysics of Orai store-operated Ca2+ channels.
AB  - Upon endoplasmic reticulum Ca(2+) store depletion, Orai channels in the plasma
      membrane are activated directly by endoplasmic reticulum-resident STIM proteins
      to generate the Ca(2+)-selective, Ca(2+) release-activated Ca(2+) (CRAC) current.
      After the molecular identification of Orai, a plethora of functional and
      biochemical studies sought to compare Orai homologs, determine their
      stoichiometry, identify structural domains responsible for the biophysical
      fingerprint of the CRAC current, identify the physiological functions, and
      investigate Orai homologs as potential therapeutic targets. Subsequently, the
      solved crystal structure of Drosophila Orai (dOrai) substantiated many findings
      from structure-function studies, but also revealed an unexpected hexameric
      structure. In this review, we explore Orai channels as elucidated by functional
      and biochemical studies, analyze the dOrai crystal structure and its implications
      for Orai channel function, and present newly available information from molecular
      dynamics simulations that shed light on Orai channel gating and permeation. 

PMID- 25606674
TI  - Spatiotemporal detection and analysis of exocytosis reveal fusion "hotspots"
      organized by the cytoskeleton in endocrine cells.
AB  - Total internal reflection fluorescence microscope has often been used to study
      the molecular mechanisms underlying vesicle exocytosis. However, the spatial
      occurrence of the fusion events within a single cell is not frequently explored
      due to the lack of sensitive and accurate computer-assisted programs to analyze
      large image data sets. Here, we have developed an image analysis platform for the
      nonbiased identification of different types of vesicle fusion events with high
      accuracy in different cell types. By performing spatiotemporal analysis of
      stimulus-evoked exocytosis in insulin-secreting INS-1 cells, we statistically
      prove that individual vesicle fusion events are clustered at hotspots. This
      spatial pattern disappears upon the disruption of either the actin or the
      microtubule network; this disruption also severely inhibits evoked exocytosis. By
      demonstrating that newcomer vesicles are delivered from the cell interior to the
      surface membrane for exocytosis, we highlight a previously unappreciated
      mechanism in which the cytoskeleton-dependent transportation of secretory
      vesicles organizes exocytosis hotspots in endocrine cells. 

PMID- 25606675
TI  - Functional rearrangement of the light-harvesting antenna upon state transitions
      in a green alga.
AB  - State transitions in the green alga Chlamydomonas reinhardtii serve to balance
      excitation energy transfer to photosystem I (PSI) and to photosystem II (PSII)
      and possibly play a role as a photoprotective mechanism. Thus, light-harvesting
      complex II (LHCII) can switch between the photosystems consequently transferring
      more excitation energy to PSII (state 1) or to PSI (state 2) or can end up in
      LHCII-only domains. In this study, low-temperature (77 K) steady-state and time
      resolved fluorescence measured on intact cells of Chlamydomonas reinhardtii shows
      that independently of the state excitation energy transfer from LHCII to PSI or
      to PSII occurs on two main timescales of <15 ps and ~ 100 ps. Moreover, in state
      1 almost all LHCIIs are functionally connected to PSII, whereas the transition
      from state 1 to a state 2 chemically locked by 0.1 M sodium fluoride leads to an
      almost complete functional release of LHCIIs from PSII. About 2/3 of the released
      LHCIIs transfer energy to PSI and ~ 1/3 of the released LHCIIs form a component
      designated X-685 peaking at 685 nm that decays with time constants of 0.28 and
      5.8 ns and does not transfer energy to PSI or to PSII. A less complete state 2
      was obtained in cells incubated under anaerobic conditions without chemical
      locking. In this state about half of all LHCIIs remained functionally connected
      to PSII, whereas the remaining half became functionally connected to PSI or
      formed X-685 in similar amounts as with chemical locking. We demonstrate that X
      685 originates from LHCII domains not connected to a photosystem and that its
      presence introduces a change in the interpretation of 77 K steady-state
      fluorescence emission measured upon state transitions in Chalamydomonas
      reinhardtii.

PMID- 25606676
TI  - Effect of thanatophoric dysplasia type I mutations on FGFR3 dimerization.
AB  - Thanatophoric dysplasia type I (TDI) is a lethal human skeletal growth disorder
      with a prevalence of 1 in 20,000 to 1 in 50,000 births. TDI is known to arise
      because of five different mutations, all involving the substitution of an amino
      acid with a cysteine in fibroblast growth factor receptor 3 (FGFR3). Cysteine
      mutations in receptor tyrosine kinases (RTKs) have been previously proposed to
      induce constitutive dimerization in the absence of ligand, leading to receptor
      overactivation. However, their effect on RTK dimer stability has never been
      measured experimentally. In this study, we characterize the effect of three TDI
      mutations, Arg248Cys, Ser249Cys, and Tyr373Cys, on FGFR3 dimerization in
      mammalian membranes, in the absence of ligand. We demonstrate that the mutations
      lead to surprisingly modest dimer stabilization and to structural perturbations
      of the dimers, challenging the current understanding of the molecular
      interactions that underlie TDI. 

PMID- 25606677
TI  - Molecular model for the solubilization of membranes into nanodisks by styrene
      maleic Acid copolymers.
AB  - A recent discovery in membrane research is the ability of styrene-maleic acid
      (SMA) copolymers to solubilize membranes in the form of nanodisks allowing
      extraction and purification of membrane proteins from their native environment in
      a single detergent-free step. This has important implications for membrane
      research because it allows isolation as well as characterization of proteins and
      lipids in a near-native environment. Here, we aimed to unravel the molecular mode
      of action of SMA copolymers by performing systematic studies using model
      membranes of varying compositions and employing complementary biophysical
      approaches. We found that the SMA copolymer is a highly efficient membrane
      solubilizing agent and that lipid bilayer properties such as fluidity, thickness,
      lateral pressure profile, and charge density all play distinct roles in the
      kinetics of solubilization. More specifically, relatively thin membranes,
      decreased lateral chain pressure, low charge density at the membrane surface, and
      increased salt concentration promote the speed and yield of vesicle
      solubilization. Experiments using a native membrane lipid extract showed that the
      SMA copolymer does not discriminate between different lipids and thus retains the
      native lipid composition in the solubilized particles. A model is proposed for
      the mode of action of SMA copolymers in which membrane solubilization is mainly
      driven by the hydrophobic effect and is further favored by physical properties of
      the polymer such as its relatively small cross-sectional area and rigid pendant
      groups. These results may be helpful for development of novel applications for
      this new type of solubilizing agent, and for optimization of the SMA technology
      for solubilization of the wide variety of cell membranes found in nature. 

PMID- 25606678
TI  - Irrelevance of the power stroke for the directionality, stopping force, and
      optimal efficiency of chemically driven molecular machines.
AB  - A simple model for a chemically driven molecular walker shows that the elastic
      energy stored by the molecule and released during the conformational change known
      as the power-stroke (i.e., the free-energy difference between the pre- and post
      power-stroke states) is irrelevant for determining the directionality, stopping
      force, and efficiency of the motor. Further, the apportionment of the dependence
      on the externally applied force between the forward and reverse rate constants of
      the power-stroke (or indeed among all rate constants) is irrelevant for
      determining the directionality, stopping force, and efficiency of the motor.
      Arguments based on the principle of microscopic reversibility demonstrate that
      this result is general for all chemically driven molecular machines, and even
      more broadly that the relative energies of the states of the motor have no role
      in determining the directionality, stopping force, or optimal efficiency of the
      machine. Instead, the directionality, stopping force, and optimal efficiency are
      determined solely by the relative heights of the energy barriers between the
      states. Molecular recognition--the ability of a molecular machine to discriminate
      between substrate and product depending on the state of the machine--is far more
      important for determining the intrinsic directionality and thermodynamics of
      chemo-mechanical coupling than are the details of the internal mechanical
      conformational motions of the machine. In contrast to the conclusions for
      chemical driving, a power-stroke is very important for the directionality and
      efficiency of light-driven molecular machines and for molecular machines driven
      by external modulation of thermodynamic parameters.

PMID- 25606679
TI  - Orientation of the N- and C-terminal lobes of the myosin regulatory light chain
      in cardiac muscle.
AB  - The orientations of the N- and C-terminal lobes of the cardiac isoform of the
      myosin regulatory light chain (cRLC) in the fully dephosphorylated state in
      ventricular trabeculae from rat heart were determined using polarized
      fluorescence from bifunctional sulforhodamine probes. cRLC mutants with one of
      eight pairs of surface-accessible cysteines were expressed, labeled with
      bifunctional sulforhodamine, and exchanged into demembranated trabeculae to
      replace some of the native cRLC. Polarized fluorescence data from the probes in
      each lobe were combined with RLC crystal structures to calculate the lobe
      orientation distribution with respect to the filament axis. The orientation
      distribution of the N-lobe had three distinct peaks (N1-N3) at similar angles in
      relaxation, isometric contraction, and rigor. The orientation distribution of the
      C-lobe had four peaks (C1-C4) in relaxation and isometric contraction, but only
      two of these (C2 and C4) remained in rigor. The N3 and C4 orientations are close
      to those of the corresponding RLC lobes in myosin head fragments bound to
      isolated actin filaments in the absence of ATP (in rigor), but also close to
      those of the pair of heads folded back against the filament surface in isolated
      thick filaments in the so-called J-motif conformation. The N1 and C1 orientations
      are close to those expected for actin-bound myosin heads with their light chain
      domains in a pre-powerstroke conformation. The N2 and C3 orientations have not
      been observed previously. The results show that the average change in orientation
      of the RLC region of the myosin heads on activation of cardiac muscle is small;
      the RLC regions of most heads remain in the same conformation as in relaxation.
      This suggests that the orientation of the dephosphorylated RLC region of myosin
      heads in cardiac muscle is primarily determined by an interaction with the thick
      filament surface. 

PMID- 25606680
TI  - Continuous allosteric regulation of a viral packaging motor by a sensor that
      detects the density and conformation of packaged DNA.
AB  - We report evidence for an unconventional type of allosteric regulation of a
      biomotor. We show that the genome-packaging motor of phage phi29 is regulated by
      a sensor that detects the density and conformation of the DNA packaged inside the
      viral capsid, and slows the motor by a mechanism distinct from the effect of a
      direct load force on the motor. Specifically, we show that motor-ATP interactions
      are regulated by a signal that is propagated allosterically from inside the viral
      shell to the motor mounted on the outside. This signal continuously regulates the
      motor speed and pausing in response to changes in either density or conformation
      of the packaged DNA, and slows the motor before the buildup of large forces
      resisting DNA confinement. Analysis of motor slipping reveals that the force
      resisting packaging remains low (<1 pN) until ~ 70% and then rises sharply to ~
      23 pN at high filling, which is a several-fold lower value than was previously
      estimated under the assumption that force alone slows the motor. These findings
      are consistent with recent studies of the stepping kinetics of the motor. The
      allosteric regulatory mechanism we report allows double-stranded DNA viruses to
      achieve rapid, high-density packing of their genomes by limiting the buildup of
      nonequilibrium load forces on the motor.

PMID- 25606681
TI  - Phosphorylation in the catalytic cleft stabilizes and attracts domains of a
      phosphohexomutase.
AB  - Phosphorylation can modulate the activities of enzymes. The phosphoryl donor in
      the catalytic cleft of alpha-D-phosphohexomutases is transiently dephosphorylated
      while the reaction intermediate completes a 180 degrees  reorientation within the
      cleft. The phosphorylated form of 52 kDa bacterial
      phosphomannomutase/phosphoglucomutase is less accessible to dye or protease, more
      stable to chemical denaturation, and widely stabilized against NMR-detected
      hydrogen exchange across the core of domain 3 to juxtaposed domain 4 (each by >=
      1.3 kcal/mol) and parts of domains 1 and 2. However, phosphorylation accelerates
      hydrogen exchange in specific regions of domains 1 and 2, including a metal
      binding residue in the active site. Electrostatic field lines reveal attraction
      across the catalytic cleft between phosphorylated Ser-108 and domain 4, but
      repulsion when Ser-108 is dephosphorylated. Molecular dynamics (MD) simulated the
      dephosphorylated form to be expanded due to enhanced rotational freedom of domain
      4. The contacts and fluctuations of the MD trajectories enabled correct
      simulation of more than 80% of sites that undergo either protection or
      deprotection from hydrogen exchange due to phosphorylation. Electrostatic
      attraction in the phosphorylated enzyme accounts for 1) domain 4 drawing closer
      to domains 1 and 3; 2) decreased accessibility; and 3) increased stability within
      these domains. The electrostriction due to phosphorylation may help capture
      substrate, whereas the opening of the cleft upon transient dephosphorylation
      allows rotation of the intermediate. The long-range effects of phosphorylation on
      hydrogen exchange parallel reports on protein kinases, suggesting a conceptual
      link among these multidomain, phosphoryl transfer enzymes.

PMID- 25606682
TI  - Biophysical analysis of the MHR motif in folding and domain swapping of the HIV
      capsid protein C-terminal domain.
AB  - Infection by human immunodeficiency virus (HIV) depends on the function, in
      virion morphogenesis and other stages of the viral cycle, of a highly conserved
      structural element, the major homology region (MHR), within the carboxyterminal
      domain (CTD) of the capsid protein. In a modified CTD dimer, MHR is swapped
      between monomers. While no evidence for MHR swapping has been provided by
      structural models of retroviral capsids, it is unknown whether it may occur
      transiently along the virus assembly pathway. Whatever the case, the MHR-swapped
      dimer does provide a novel target for the development of anti-HIV drugs based on
      the concept of trapping a nonnative capsid protein conformation. We have carried
      out a thermodynamic and kinetic characterization of the domain-swapped CTD dimer
      in solution. The analysis includes a dissection of the role of conserved MHR
      residues and other amino acids at the dimerization interface in CTD folding,
      stability, and dimerization by domain swapping. The results revealed some
      energetic hotspots at the domain-swapped interface. In addition, many MHR
      residues that are not in the protein hydrophobic core were nevertheless found to
      be critical for folding and stability of the CTD monomer, which may dramatically
      slow down the swapping reaction. Conservation of MHR residues in retroviruses did
      not correlate with their contribution to domain swapping, but it did correlate
      with their importance for stable CTD folding. Because folding is required for
      capsid protein function, this remarkable MHR-mediated conformational
      stabilization of CTD may help to explain the functional roles of MHR not only
      during immature capsid assembly but in other processes associated with retrovirus
      infection. This energetic dissection of the dimerization interface in MHR-swapped
      CTD may also facilitate the design of anti-HIV compounds that inhibit capsid
      assembly by conformational trapping of swapped CTD dimers. 

PMID- 25606684
TI  - Small peptide binding stiffens the ubiquitin-like protein SUMO1.
AB  - Posttranslational modification by small ubiquitin-like modifiers (SUMOs), known
      as SUMOylation, is a key regulatory event in many eukaryotic cellular processes
      in which SUMOs interact with a large number of target proteins. SUMO binding
      motifs (SBMs) are small peptides derived from these target proteins that interact
      noncovalently with SUMOs and induce conformational changes. To determine the
      effect of SBMs on the mechanical properties of SUMO1 (the first member of the
      human SUMO family), we performed single-molecule force spectroscopy experiments
      on SUMO1/SBM complexes. The unfolding force of SUMO1 (at a pulling speed of 400
      nm/s) increased from ~ 130 pN to ~ 170 pN upon binding to SBMs, indicating
      mechanical stabilization upon complexation. Pulling-speed-dependent experiments
      and Monte Carlo simulations measured a large decrease in distance to the
      unfolding transition state for SUMO1 upon SBM binding, which is by far the
      largest change measured for any ligand binding protein. The stiffness of SUMO1
      (measured as a spring constant for the deformation response along the line
      joining the N- and C-termini) increased upon SBM binding from ~ 1 N/m to ~ 3.5
      N/m. The relatively higher flexibility of ligand-free SUMO1 might play a role in
      accessing various conformations before binding to a target.

PMID- 25606683
TI  - Single-molecule motions of MHC class II rely on bound peptides.
AB  - The major histocompatibility complex (MHC) class II protein can bind peptides of
      different lengths in the region outside the peptide-binding groove. Peptide
      flanking residues (PFRs) contribute to the binding affinity of the peptide for
      MHC and change the immunogenicity of the peptide/MHC complex with regard to T
      cell receptor (TCR). The mechanisms underlying these phenomena are currently
      unknown. The molecular flexibility of the peptide/MHC complex may be an important
      determinant of the structures recognized by certain T cells. We used single
      molecule x-ray analysis (diffracted x-ray tracking (DXT)) and fluorescence
      anisotropy to investigate these mechanisms. DXT enabled us to monitor the real
      time Brownian motion of the peptide/MHC complex and revealed that peptides
      without PFRs undergo larger rotational motions than peptides with PFRs.
      Fluorescence anisotropy further revealed that peptides without PFRs exhibit
      slightly larger motions on the nanosecond timescale. These results demonstrate
      that peptides without PFRs undergo dynamic motions in the groove of MHC and
      consequently are able to assume diverse structures that can be recognized by T
      cells.

PMID- 25606685
TI  - Equilibrium kinetic network of the villin headpiece in implicit solvent.
AB  - We applied the single-replica multiple-state transition-interface sampling method
      to elucidate the equilibrium kinetic network of the 35-residue-fragment (HP-35)
      villin headpiece in implicit water at room temperature. Starting from the native
      Protein Data Bank structure, nine (meta)stable states of the system were
      identified, from which the kinetic network was built by sampling pathways between
      these states. Application of transition path theory allowed analysis of the
      (un)folding mechanism. The resulting (un)folding rates agree well with
      experiments. This work demonstrates that high (un)folding barriers can now be
      studied. 

PMID- 25606686
TI  - Stigmatellin probes the electrostatic potential in the QB site of the
      photosynthetic reaction center.
AB  - The electrostatic potential in the secondary quinone (QB) binding site of the
      reaction center (RC) of the photosynthetic bacterium Rhodobacter sphaeroides
      determines the rate and free energy change (driving force) of electron transfer
      to QB. It is controlled by the ionization states of residues in a strongly
      interacting cluster around the QB site. Reduction of the QB induces change of the
      ionization states of residues and binding of protons from the bulk. Stigmatellin,
      an inhibitor of the mitochondrial and photosynthetic respiratory chain, has been
      proven to be a unique voltage probe of the QB binding pocket. It binds to the QB
      site with high affinity, and the pK value of its phenolic group monitors the
      local electrostatic potential with high sensitivity. Investigations with
      different types of detergent as a model system of isolated RC revealed that the
      pK of stigmatellin was controlled overwhelmingly by electrostatic and slightly by
      hydrophobic interactions. Measurements showed a high pK value (>11) of
      stigmatellin in the QB pocket of the dark-state wild-type RC, indicating
      substantial negative potential. When the local electrostatics of the QB site was
      modulated by a single mutation, L213Asp -> Ala, or double mutations, L213Asp
      L212Glu -> Ala-Ala (AA), the pK of stigmatellin dropped to 7.5 and 7.4,
      respectively, which corresponds to a >210 mV increase in the electrostatic
      potential relative to the wild-type RC. This significant pK drop (DeltapK > 3.5)
      decreased dramatically to (DeltapK > 0.75) in the RC of the compensatory mutant
      (AA+M44Asn -> AA+M44Asp). Our results indicate that the L213Asp is the most
      important actor in the control of the electrostatic potential in the QB site of
      the dark-state wild-type RC, in good accordance with conclusions of former
      studies using theoretical calculations or light-induced charge recombination
      assay.

PMID- 25606687
TI  - Effects of HCM cTnI mutation R145G on troponin structure and modulation by PKA
      phosphorylation elucidated by molecular dynamics simulations.
AB  - Cardiac troponin (cTn) is a key molecule in the regulation of human cardiac
      muscle contraction. The N-terminal cardiac-specific peptide of the inhibitory
      subunit of troponin, cTnI (cTnI(1-39)), is a target for phosphorylation by
      protein kinase A (PKA) during beta-adrenergic stimulation. We recently presented
      evidence indicating that this peptide interacts with the inhibitory peptide
      (cTnl(137-147)) when S23 and S24 are phosphorylated. The inhibitory peptide is
      also the target of the point mutation cTnI-R145G, which is associated with
      hypertrophic cardiomyopathy (HCM), a disease associated with sudden death in
      apparently healthy young adults. It has been shown that both phosphorylation and
      this mutation alter the cTnC-cTnI (C-I) interaction, which plays a crucial role
      in modulating contractile activation. However, little is known about the
      molecular-level events underlying this modulation. Here, we computationally
      investigated the effects of the cTnI-R145G mutation on the dynamics of cTn, cTnC
      Ca(2+) handling, and the C-I interaction. Comparisons were made with the cTnI
      R145G/S23D/S24D phosphomimic mutation, which has been used both experimentally
      and computationally to study the cTnI N-terminal specific effects of PKA
      phosphorylation. Additional comparisons between the phosphomimic mutations and
      the real phosphorylations were made. For this purpose, we ran triplicate 150 ns
      molecular dynamics simulations of cTnI-R145G Ca(2+)-bound cTnC(1-161)-cTnI(1-172)
      cTnT(236-285), cTnI-R145G/S23D/S24D Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236
      285), and cTnI-R145G/PS23/PS24 Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236
      285), respectively. We found that the cTnI-R145G mutation did not impact the
      overall dynamics of cTn, but stabilized crucial Ca(2+)-coordinating interactions.
      However, the phosphomimic mutations increased overall cTn fluctuations and
      destabilized Ca(2+) coordination. Interestingly, cTnI-R145G blunted the
      intrasubunit interactions between the cTnI N-terminal extension and the cTnI
      inhibitory peptide, which have been suggested to play a crucial role in
      modulating troponin function during beta-adrenergic stimulation. These findings
      offer a molecular-level explanation for how the HCM mutation cTnI-R145G reduces
      the modulation of cTn by phosphorylation of S23/S24 during beta-adrenergic
      stimulation.

PMID- 25606688
TI  - Determination of the catalytic mechanism for mitochondrial malate dehydrogenase.
AB  - The kinetics of malate dehydrogenase (MDH) catalyzed oxidation/reduction of L
      malate/oxaloacetate is pH-dependent due to the proton generated/taken up during
      the reaction. Previous kinetic studies on the mitochondrial MDH did not yield a
      consensus kinetic model that explains both substrate and pH dependency of the
      initial velocity. In this study, we propose, to our knowledge, a new kinetic
      mechanism to explain kinetic data acquired over a range of pH and substrate
      concentrations. Progress curves in the forward and reverse reaction directions
      were obtained under a variety of reactant concentrations to identify associated
      kinetic parameters. Experiments were conducted at physiologically relevant ionic
      strength of 0.17 M, pH ranging between 6.5 and 9.0, and at 25  degrees C. The
      developed model was built on the prior observation of proton uptake upon binding
      of NADH to MDH, and that the MDH-catalyzed oxidation of NADH may follow an
      ordered bi-bi mechanism with NADH/NAD binding to the enzyme first, followed by
      the binding of oxaloacetate/L-malate. This basic mechanism was expanded to
      account for additional ionic states to explain the pH dependency of the kinetic
      behavior, resulting in what we believe to be the first kinetic model explaining
      both substrate and pH dependency of the reaction velocity.

PMID- 25606689
TI  - Characterization of the kinetics of cardiac cytosolic malate dehydrogenase and
      comparative analysis of cytosolic and mitochondrial isoforms.
AB  - Because the mitochondrial inner membrane is impermeable to pyridine nucleotides,
      transport of reducing equivalents between the mitochondrial matrix and the
      cytoplasm relies on shuttle mechanisms, including the malate-aspartate shuttle
      and the glycerol-3-phosphate shuttle. These shuttles are needed for reducing
      equivalents generated by metabolic reactions in the cytosol to be oxidized via
      aerobic metabolism. Two isoenzymes of malate dehydrogenase (MDH) operate as
      components of the malate-aspartate shuttle, in which a reducing equivalent is
      transported via malate, which when oxidized to oxaloacetate, transfers an
      electron pair to reduce NAD to NADH. Several competing mechanisms have been
      proposed for the MDH-catalyzed reaction. This study aims to identify the pH
      dependent kinetic mechanism for cytoplasmic MDH (cMDH) catalyzed
      oxidation/reduction of MAL/OAA. Experiments were conducted assaying the forward
      and reverse directions with products initially present, varying pH between 6.5
      and 9.0. By fitting time-course data to various mechanisms, it is determined that
      an ordered bi-bi mechanism with coenzyme binding first followed by the binding of
      substrate is able to explain the kinetic data. The proposed mechanism is similar
      to, but not identical to, the mechanism recently determined for the mitochondrial
      isoform, mMDH. cMDH and mMDH mechanisms are also shown to both be reduced
      versions of a common, more complex mechanism that can explain the kinetic data
      for both isoforms. Comparing the simulated activity (ratio of initial velocity to
      the enzyme concentration) under physiological conditions, the mitochondrial MDH
      (mMDH) activity is predicted to be higher than cMDH activity under mitochondrial
      matrix conditions while the cMDH activity is higher than mMDH activity under
      cytoplasmic conditions, suggesting that the functions of the isoforms are
      kinetically tuned to their individual physiological roles. 

PMID- 25606690
TI  - Stochastic interdigitation as a toughening mechanism at the interface between
      tendon and bone.
AB  - Reattachment and healing of tendon to bone poses a persistent clinical challenge
      and often results in poor outcomes, in part because the mechanisms that imbue the
      uninjured tendon-to-bone attachment with toughness are not known. One feature of
      typical tendon-to-bone surgical repairs is direct attachment of tendon to smooth
      bone. The native tendon-to-bone attachment, however, presents a rough mineralized
      interface that might serve an important role in stress transfer between tendon
      and bone. In this study, we examined the effects of interfacial roughness and
      interdigital stochasticity on the strength and toughness of a bimaterial
      interface. Closed form linear approximations of the amplification of stresses at
      the rough interface were derived and applied in a two-dimensional unit-cell
      model. Results demonstrated that roughness may serve to increase the toughness of
      the tendon-to-bone insertion site at the expense of its strength. Results further
      suggested that the natural tendon-to-bone attachment presents roughness for which
      the gain in toughness outweighs the loss in strength. More generally, our results
      suggest a pathway for stochasticity to improve surgical reattachment strategies
      and structural engineering attachments. 

PMID- 25606692
TI  - Impaired bone morphogenetic protein receptor II signaling in a transforming
      growth factor-beta-dependent mouse model of pulmonary hypertension and in
      systemic sclerosis.
AB  - RATIONALE: Up to 10% of patients with systemic sclerosis (SSc) develop pulmonary
      arterial hypertension (PAH). This risk persists throughout the disease and is
      time dependent, suggesting that SSc is a susceptibility factor. Outcome for SSc
      PAH is poor compared with heritable or idiopathic forms, despite clinical and
      pathological similarities. Although susceptibility in heritable PAH and
      idiopathic PAH is strongly associated with gene mutations leading to reduced
      expression of bone morphogenetic protein receptor (BMPR) II, these mutations have
      not been observed in SSc-PAH. OBJECTIVES: To explore BMPRII expression and
      function in a mouse model of SSc (TbetaRIIDeltak-fib) that is susceptible to
      developing pulmonary hypertension and in SSc lung. METHODS: BMPRII and downstream
      signaling pathways were profiled in lung tissue and fibroblasts from the
      TbetaRIIDeltak-fib model, which develops pulmonary vasculopathy with pulmonary
      hypertension that is exacerbated by SU5416. Complementary studies examined SSc or
      control lung tissue and fibroblasts. MEASUREMENTS AND MAIN RESULTS: Our study
      shows reduced BMPRII, impaired signaling, and altered receptor turnover activity
      in a transforming growth factor (TGF)-beta-dependent mouse model of SSc-PAH.
      Similarly, a significant reduction in BMPRII expression is observed in SSc lung
      tissue and fibroblasts. Increased proteasomal degradation of BMPRII appears to
      underlie this and may result from heightened TGF-beta activity. CONCLUSIONS: We
      found reduced BMPRII protein in patients with SSc-PAH and a relevant mouse model
      associated with increased proteasomal degradation of BMPRII. Collectively, these
      results suggest that impaired BMP signaling, resulting from TGF-beta-dependent
      increased receptor degradation, may promote PAH susceptibility in SSc and provide
      a unifying mechanism across different forms of PAH.

PMID- 25606691
TI  - Is catalytic activity of chaperones a selectable trait for the emergence of heat
      shock response?
AB  - Although heat shock response is ubiquitous in bacterial cells, the underlying
      physical chemistry behind heat shock response remains poorly understood. To study
      the response of cell populations to heat shock we employ a physics-based ab
      initio model of living cells where protein biophysics (i.e., folding and protein
      protein interactions in crowded cellular environments) and important aspects of
      proteins homeostasis are coupled with realistic population dynamics simulations.
      By postulating a genotype-phenotype relationship we define a cell division rate
      in terms of functional concentrations of proteins and protein complexes, whose
      Boltzmann stabilities of folding and strengths of their functional interactions
      are exactly evaluated from their sequence information. We compare and contrast
      evolutionary dynamics for two models of chaperon action. In the active model,
      foldase chaperones function as nonequilibrium machines to accelerate the rate of
      protein folding. In the passive model, holdase chaperones form reversible
      complexes with proteins in their misfolded conformations to maintain their
      solubility. We find that only cells expressing foldase chaperones are capable of
      genuine heat shock response to the increase in the amount of unfolded proteins at
      elevated temperatures. In response to heat shock, cells' limited resources are
      redistributed differently for active and passive models. For the active model,
      foldase chaperones are overexpressed at the expense of downregulation of high
      abundance proteins, whereas for the passive model; cells react to heat shock by
      downregulating their high abundance proteins, as their low abundance proteins are
      upregulated. 

PMID- 25606693
TI  - Diagnostic accuracy of language sample measures with Persian-speaking preschool
      children.
AB  - This study examined the diagnostic accuracy of selected language sample measures
      (LSMs) with Persian-speaking children. A pre-accuracy study followed by phase I
      and II studies are reported. Twenty-four Persian-speaking children, aged 42 to 54
      months, with primary language impairment (PLI) were compared to 27 age-matched
      children without PLI on a set of measures derived from play-based, conversational
      language samples. Results showed that correlations between age and LSMs were not
      statistically significant in either group of children. However, a majority of
      LSMs differentiated children with and without PLI at the group level (phase I),
      while three of the measures exhibited good diagnostic accuracy at the level of
      the individual (phase II). We conclude that general LSMs are promising for
      distinguishing between children with and without PLI. Persian-specific measures
      are mainly helpful in identifying children without language impairment while
      their ability to identify children with PLI is poor.

PMID- 25606694
TI  - Rising above the rhetoric: mobile applications and the delivery of cost-effective
      cardiovascular care in resource-limited settings.

PMID- 25606695
TI  - Early invasive treatment for acute coronary syndrome in patients with chronic
      kidney disease: do we know what we're doing?

PMID- 25606696
TI  - Endogenous carbon monoxide and cardiometabolic risk: can measuring exhaled carbon
      monoxide be used to refine cardiometabolic risk assessment?

PMID- 25606697
TI  - ATLANTIC and beyond: an interview with Professor Azfar Zaman.
AB  - Professor Azfar Zaman speaks to Wing Wu, Commissioning Editor: Professor Azfar
      Zaman is a Consultant Interventional Cardiologist at Freeman Hospital and
      Professor of Cardiology at Newcastle University. Following graduation at Leeds
      Medical School, he completed postgraduate training in cardiology at regional
      centres in Leeds, London and Cardiff. Prior to his appointment in Newcastle upon
      Tyne, he was a Fulbright Scholar and British Heart Foundation International
      Fellow at Mount Sinai Medical Center, New York, USA. He is the Clinical Lead for
      Coronary Intervention and Director of the Cardiac Catheter Laboratories. In 2012,
      he was appointed Specialty Group Lead for Cardiovascular Research and has an
      interest in clinical research, with a particular interest in atherothrombosis in
      diabetes and clinical trials. 

PMID- 25606698
TI  - Short-term dual antiplatelet therapy in patients with acute coronary syndrome
      treated with the COMBOTM dual-therapy stent: what we plan to learn from REDUCE.

PMID- 25606699
TI  - Takotsubo's cardiomyopathy with an uncommon complication: implications for
      management and treatment.
AB  - We present the case of a 57-year-old female with no significant history of
      cardiac disease admitted to our service with stress-induced cardiomyopathy
      (Takotsubo's cardiomyopathy). Admission echocardiography with contrast showed a
      non-mobile apical-filling defect, consistent with laminar thrombus. After 1 month
      of anticoagulation with warfarin (bridged with inpatient intravenous heparin),
      follow-up echocardiography with contrast showed resolution of the thrombus.
      Although reported in the literature, to our knowledge, there are no consensus
      guidelines for the surveillance and treatment of left ventricular thrombus in
      patients with Takotsubo's cardiomyopathy. An awareness of this adverse effect and
      its treatment implications is imperative for any clinician caring for these
      patients.

PMID- 25606700
TI  - ODYSSEY MONO: effect of alirocumab 75 mg subcutaneously every 2 weeks as
      monotherapy versus ezetimibe over 24 weeks.
AB  - ABSTRACT  Alirocumab is a fully human monoclonal antibody to PCSK9. The ODYSSEY
      MONO study was the first alirocumab Phase III study to test a previously unused
      dose of 75 mg subcutaneously every 2 weeks in a population on no lipid-lowering
      therapy. A total of 103 patients were randomly assigned to alirocumab starting at
      75 mg subcutaneously every 2 weeks or ezetimibe 10 mg per os every day with
      alirocumab dose uptitration at 12 weeks based on achieved LDL-cholesterol level
      at week 8 and followed to week 24. At the week-24 primary end point, the
      alirocumab intent-to-treat group showed a 47.2% (least square [LS] mean)
      reduction in LDL-cholesterol compared with a 15.6% (LS mean) reduction with
      ezetimibe (LS mean difference of 31.6%; p < 0.0001). Safety parameters and
      adverse events were similar between the two groups. 

PMID- 25606701
TI  - The Bologna experience with the ThoraflexTM hybrid frozen elephant trunk device.
AB  - BACKGROUND: We present our initial experience with the frozen elephant trunk
      using a ThoraflexTM hybrid device for the treatment of the complex thoracic aorta
      lesions. MATERIALS & METHODS: Between March 2013 and March 2014, ten patients
      underwent thoracic aorta surgery using the frozen elephant trunk approach with
      the Thoraflex hybrid device. Indications for surgery were: residual type A
      chronic dissection (eight patients), degenerative aneurysm (one patient) and type
      B chronic aortic dissection (one patient). Selective antegrade cerebral perfusion
      and moderate hypothermia were used in all cases. RESULTS: In-hospital mortality
      was 0% and no patients presented with paraplegia, paraparesis or major
      neurological events. One patient experienced transient ischemic attack. Two
      patients underwent reoperation for bleeding. All postoperative angiography CT
      scans confirmed the desired results. CONCLUSION: Our initial experience
      demonstrated excellent early results. The Thoraflex hybrid prosthesis with the
      four-branched arch graft increases the spectrum of techniques available for the
      surgeon in the treatment of complex diseases of the thoracic aorta.

PMID- 25606702
TI  - Vascular injury and repair: a potential target for cell therapies.
AB  - Whether due to atherosclerotic disease or mechanical intervention, vascular
      injury is a frequently encountered pathology in cardiovascular medicine. The past
      decade has seen growing interest in the role of circulating endothelial
      progenitor cells in vessel recovery postinjury. Despite this, the definition,
      origin and potential role of endothelial progenitor cells in vascular
      regeneration remains highly controversial. While animal work has shown early
      promise, evidence of a therapeutic role for endothelial progenitor cells in
      humans remains elusive. To date, clinical trials involving direct cell
      administration, growth factor therapy and endothelial cell capture stents have
      largely been disappointing, although this may in part reflect limitations in
      study design. This article will outline the pathophysiological mechanisms of
      vascular injury with an emphasis on endothelial progenitor cell biology and the
      potential therapeutic role of this exciting new field.

PMID- 25606703
TI  - Mechanisms of myocardial ischemia-reperfusion injury and the cytoprotective role
      of minocycline: scope and limitations.
AB  - Deep insight into the complex mechanisms of myocardial ischemia-reperfusion
      injury has been attained in the past years. Minocycline is a second-generation
      tetracycline with US FDA approval for clinical use in various infections. Lately,
      several noninfectious cytoprotective activities of minocycline have been
      discovered as well. There now exists encouraging evidence of its protective role
      in cardiovascular pathology and its activity against myocardial ischemia
      reperfusion injury. In this article, an overview of the major mechanisms involved
      in myocardial ischemia-reperfusion injury is presented. This is followed by an
      analysis of the mechanisms by which minocycline exerts its cytoprotective role
      and of studies that have been conducted in order to analyze minocycline, along
      with a review of the scope and limitations of its role as a cytoprotective agent.

PMID- 25606704
TI  - Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage.
AB  - Cardiac manifestations are recognized complications of subarachnoid hemorrhage.
      Neurogenic stress cardiomyopathy is one complication that is seen in acute
      subarachnoid hemorrhage. It can present as transient diffuse left ventricular
      dysfunction or as transient regional wall motion abnormalities. It occurs more
      frequently with neurologically severe-grade subarachnoid hemorrhage and is
      associated with increased morbidity and poor clinical outcomes. Managing this
      subset of patients is challenging. Early identification followed by a
      multidisciplinary team approach can potentially improve outcomes.

PMID- 25606705
TI  - Use and impact of cardiac medication during pregnancy.
AB  - Cardiovascular disease is the most encountered cause of maternal death during
      pregnancy in the western world and an increase in maternal mortality due to
      cardiac causes has been observed. More women with congenital or acquired heart
      disease have the desire to become pregnant. Pregnancy is known to impose a major
      hemodynamic burden and also has impacts on the coagulation system. The risk of
      developing complications is clearly increased as compared with the normal
      population. For optimal management, it is crucial to have information on the
      effects of cardiac medications on the fetus. The focus of this article is to
      discuss the management of cardiac disease in pregnancy, as well as the known
      safety of cardiac medications for the mother and/or fetus.

PMID- 25606707
TI  - PET imaging of atherosclerosis.
AB  - Atherosclerosis is a chronic, progressive, multifocal disease of the arterial
      wall, which is mainly fuelled by local and systemic inflammation, often resulting
      in acute ischemic events following plaque rupture and vessel occlusion. When
      assessing the cardiovascular risk of an individual patient, we must consider both
      global measures of disease activity and local features of plaque vulnerability,
      in addition to anatomical distribution and degree of established atherosclerosis.
      These parameters cannot be measured with conventional anatomical imaging
      techniques alone, which are designed primarily to identify the presence of
      organic intraluminal obstruction in symptomatic patients. However, molecular
      imaging with PET, using specifically targeted radiolabeled probes to track active
      in vivo atherosclerotic mechanisms noninvasively, may potentially provide a
      method that is better suited for this purpose. Vascular PET imaging can help us
      to further understand aspects of plaque biology, and current evidence supports a
      future role as an emerging clinical tool for the quantification of cardiovascular
      risk in order to guide and monitor responses to antiatherosclerosis treatments
      and to distinguish high-risk plaques.

PMID- 25606706
TI  - A life course approach to cardiovascular aging.
AB  - A life course approach in epidemiology investigates the biological, behavioral
      and social pathways that link physical and social exposures and experiences
      during gestation, childhood, adolescence and adult life, and across generations,
      to later-life health and disease risk. We illustrate how a life course approach
      has been applied to cardiovascular disease, highlighting the evidence in support
      of the early origins of disease risk. We summarize how trajectories of
      cardiometabolic risk factors change over the life course and suggest that
      understanding underlying 'normal' or 'healthy' trajectories and the
      characteristics that drive deviations from such trajectories offer the potential
      for early prevention and for identifying means of preventing future disease.

PMID- 25606709
TI  - Surgical technique for graft exchange after big-bubble deep anterior lamellar
      keratoplasty.
AB  - PURPOSE: The aim of this study was to describe a surgical technique for repeat
      deep anterior lamellar keratoplasty (DALK) by baring Descemet membrane again in
      eyes affected by stromal opacity of the donor lamella. METHODS: Repeat DALK was
      performed in 5 eyes of 5 patients affected by central stromal opacity not
      involving the endothelium; indications for repeat surgery were postbacterial or
      postherpetic corneal scars (n = 3), postphotorefractive keratectomy haze (n = 1),
      and recurrence of granular dystrophy (n = 1). The surgical procedure consisted of
      the following: (1) superficial trephination, 250 MUm in depth, on the original
      peripheral scar; (2) blunt detachment of the donor graft completed by means of
      corneal forceps; (3) apposition of the new lamella. Best spectacle-corrected
      visual acuity, topographic astigmatism, and endothelial cell density were
      evaluated preoperatively, as well as 3, 6, 9, 12, and 18 months after surgery.
      RESULTS: At the latest follow-up examination, with all sutures removed from all
      eyes, the best spectacle-corrected visual acuity was 20/30 or better in all cases
      with 3 eyes achieving 20/20. Postoperative refractive astigmatism averaged 3.0 +/
      1.2 diopters (mean +/- SD); endothelial cell density was not significantly
      affected by surgery. CONCLUSIONS: Repeat DALK is effective in removing diseased
      corneal stroma while keeping the recipient endothelium unaffected; the procedure
      is simple and does not require pneumatic dissection, thus eliminating the most
      challenging surgical step; postoperative visual recovery does not differ from
      that experienced after primary DALK.

PMID- 25606708
TI  - Avoiding artefacts during electron microscopy of silver nanomaterials exposed to
      biological environments.
AB  - Electron microscopy has been applied widely to study the interaction of
      nanomaterials with proteins, cells and tissues at nanometre scale. Biological
      material is most commonly embedded in thermoset resins to make it compatible with
      the high vacuum in the electron microscope. Room temperature sample preparation
      protocols developed over decades provide contrast by staining cell organelles,
      and aim to preserve the native cell structure. However, the effect of these
      complex protocols on the nanomaterials in the system is seldom considered. Any
      artefacts generated during sample preparation may ultimately interfere with the
      accurate prediction of the stability and reactivity of the nanomaterials. As a
      case study, we review steps in the room temperature preparation of cells exposed
      to silver nanomaterials (AgNMs) for transmission electron microscopy imaging and
      analysis. In particular, embedding and staining protocols, which can alter the
      physicochemical properties of AgNMs and introduce artefacts thereby leading to a
      misinterpretation of silver bioreactivity, are scrutinized. Recommendations are
      given for the application of cryogenic sample preparation protocols, which
      simultaneously fix both particles and diffusible ions. By being aware of the
      advantages and limitations of different sample preparation methods, compromises
      or selection of different correlative techniques can be made to draw more
      accurate conclusions about the data. 

PMID- 25606710
TI  - A multiyear assessment of air quality benefits from China's emerging shale gas
      revolution: Urumqi as a case study.
AB  - China is seeking to unlock its shale gas in order to curb its notorious urban air
      pollution, but robust assessment of the impact on PM2.5 pollution of replacing
      coal with natural gas for winter heating is lacking. Here, using a whole-city
      heating energy shift opportunity offered by substantial reductions in coal
      combustion during the heating periods in Urumqi, northwest China, we conducted a
      four-year study to reveal the impact of replacing coal with natural gas on the
      mass concentrations and chemical components of PM2.5. We found a significant
      decline in PM2.5, major soluble ions and metal elements in PM2.5 in January of
      2013 and 2014 compared with the same periods in 2012 and 2011, reflecting the
      positive effects on air quality of using natural gas as a heating fuel throughout
      the city. This occurred following complete replacement with natural gas for
      heating energy in October 2012. The weather conditions during winter did not show
      any significant variation over the four years of the study. Our results indicate
      that China and other developing nations will benefit greatly from a change in
      energy source, that is, increasing the contribution of either natural gas or
      shale gas to total energy consumption with a concomitant reduction in coal
      consumption. 

PMID- 25606713
TI  - Autonoetic consciousness: Reconsidering the role of episodic memory in future
      oriented self-projection.
AB  - Following the seminal work of Ingvar (1985. "Memory for the future": An essay on
      the temporal organization of conscious awareness. Human Neurobiology, 4, 127
      136), Suddendorf (1994. The discovery of the fourth dimension: Mental time travel
      and human evolution. Master's thesis. University of Waikato, Hamilton, New
      Zealand), and Tulving (1985. Memory and consciousness. Canadian
      Psychology/PsychologieCanadienne, 26, 1-12), exploration of the ability to
      anticipate and prepare for future contingencies that cannot be known with
      certainty has grown into a thriving research enterprise. A fundamental tenet of
      this line of inquiry is that future-oriented mental time travel, in most of its
      presentations, is underwritten by a property or an extension of episodic
      recollection. However, a careful conceptual analysis of exactly how episodic
      memory functions in this capacity has yet to be undertaken. In this paper I
      conduct such an analysis. Based on conceptual, phenomenological, and empirical
      considerations, I conclude that the autonoetic component of episodic memory, not
      episodic memory per se, is the causally determinative factor enabling an
      individual to project him or herself into a personal future. 

PMID- 25606712
TI  - Numerical chromosomal instability mediates susceptibility to radiation treatment.
AB  - The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR)
      underlies an important rationale for the widely used fractionated radiation
      therapy. However, the mechanism for this cell cycle-dependent vulnerability is
      unknown. Here we show that treatment with IR leads to mitotic chromosome
      segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell
      lines. These mitotic errors generate an abundance of micronuclei that predispose
      chromosomes to subsequent catastrophic pulverization thereby independently
      amplifying radiation-induced genome damage. Experimentally suppressing whole
      chromosome missegregation reduces downstream chromosomal defects and
      significantly increases the viability of irradiated mitotic cells. Further,
      orthotopically transplanted human glioblastoma tumours in which chromosome
      missegregation rates have been reduced are rendered markedly more resistant to
      IR, exhibiting diminished markers of cell death in response to treatment. This
      work identifies a novel mitotic pathway for radiation-induced genome damage,
      which occurs outside of the primary nucleus and augments chromosomal breaks. This
      relationship between radiation treatment and whole-chromosome missegregation can
      be exploited to modulate therapeutic response in a clinically relevant manner. 

PMID- 25606715
TI  - On-road heavy-duty vehicle emissions monitoring system.
AB  - The introduction of particulate and oxides of nitrogen (NOx) after-treatment
      controls on heavy-duty vehicles has spurred the need for fleet emissions data to
      monitor their reliability and effectiveness. The University of Denver has
      developed a new method for rapidly measuring heavy-duty vehicles for gaseous and
      particulate fuel specific emissions. The method was recently used to collect 3088
      measurements at a Port of Los Angeles location and a weigh station on I-5 in
      northern California. The weigh station NOx emissions for 2014 models are 73%
      lower than 2010 models (3.8 vs 13.9 gNOx/kg of fuel) and look to continue to
      decrease with newer models. The Port site has a heavy-duty fleet that has been
      entirely equipped with diesel particulate filters since 2010. Total particulate
      mass and black carbon measurements showed that only 3% of the Port vehicles
      measured exceed expected emission limits with mean gPM/kg of fuel emissions of
      0.031 +/- 0.007 and mean gBC/kg of fuel emissions of 0.020 +/- 0.003. Mean
      particulate emissions were higher for the older weigh station fleet but 2011 and
      newer trucks gPM/kg of fuel emissions were nevertheless more than a factor of 30
      lower than the means for pre-DPF (2007 and older) model years. 

PMID- 25606716
TI  - Double-chamber microbial fuel cell with a non-platinum-group metal Fe-N-C cathode
      catalyst.
AB  - Non-Pt-group metal (non-PGM) materials based on transition metal-nitrogen-carbon
      (M-N-C) and derived from iron salt and aminoantipyrine (Fe-AAPyr) of mebendazole
      (Fe-MBZ) were studied for the first time as cathode catalysts in double-chamber
      microbial fuel cells (DCMFCs). The pH value of the cathode chamber was varied
      from 6 to 11 to elucidate the activity of those catalysts in acidic to basic
      conditions. The Fe-AAPyr- and Fe-MBZ-based cathodes were compared to a Pt-based
      cathode used as a baseline. Pt cathodes performed better at pH 6-7.5 and had
      similar performances at pH 9 and a substantially lower performance at pH 11 at
      which Fe-AAPyr and Fe-MBZ demonstrated their best electrocatalytic activity. The
      power density achieved with Pt constantly decreased from 94-99 MUW cm(-2) at pH 6
      to 55-57 MUW cm(-2) at pH 11. In contrast, the power densities of DCMFs using Fe
      AAPyr and Fe-MBZ were 61-68 MUW cm(-2) at pH 6, decreased to 51-58 MUW cm(-2) at
      pH 7.5, increased to 65-75 MUW cm(-2) at pH 9, and the highest power density was
      achieved at pH 11 (68-80 MUW cm(-2) ). Non-PGM cathode catalysts can be
      manufactured at the fraction of the cost of the Pt-based ones. The higher
      performance and lower cost indicates that non-PGM catalysts may be a viable
      materials choice in large-scale microbial fuel cells. 

PMID- 25606714
TI  - Colloidal aggregation and the in vitro activity of traditional Chinese medicines.
AB  - Traditional Chinese Medicines (TCMs) have been the sole source of therapeutics in
      China for two millennia. In recent drug discovery efforts, purified components of
      TCM formulations have shown activity in many in vitro assays, raising concerns of
      promiscuity. Here, we investigated 14 bioactive small molecules isolated from
      TCMs for colloidal aggregation. At concentrations commonly used in cell-based or
      biochemical assay conditions, eight of these compounds formed particles
      detectable by dynamic light scattering and showed detergent-reversible inhibition
      against beta-lactamase and malate dehydrogenase, two counter-screening enzymes.
      When three of these compounds were tested against their literature-reported
      molecular targets, they showed similar reversal of their inhibitory activity in
      the presence of detergent. For three of the most potent aggregators,
      contributions to promiscuity via oxidative cycling were investigated; addition of
      1 mM DTT had no effect on their activity, which is inconsistent with an oxidative
      mechanism. TCMs are often active at micromolar concentrations; this study
      suggests that care must be taken to control for artifactual activity when seeking
      their primary targets. Implications for the formulation of these molecules are
      considered. 

PMID- 25606717
TI  - Mapping the structural order of laser-induced periodic surface structures in thin
      polymer films by microfocus beam grazing incidence small-angle X-ray scattering.
AB  - In this work we present an accurate mapping of the structural order of laser
      induced periodic surface structures (LIPSS) in spin-coated thin polymer films,
      via a microfocus beam grazing incidence small-angle X-ray scattering (MUGISAXS)
      scan, GISAXS modeling, and atomic force microscopy imaging all along the scanned
      area. This combined study has allowed the evaluation of the effects on LIPSS
      formation due to nonhomogeneous spatial distribution of the laser pulse energy,
      mapping with micrometric resolution the evolution of the period and degree of
      structural order of LIPSS across the laser beam diameter in a direction
      perpendicular to the polarization vector. The experiments presented go one step
      further toward controlling nanostructure formation in LIPSS through a deep
      understanding of the parameters that influence this process. 

PMID- 25606718
TI  - Editor's note.

PMID- 25606719
TI  - The discourse of sexual excess as a hallmark of Brazilianness: revisiting
      Brazilian social thinking in the 1920s and 1930s.
AB  - The objective of this article is to analyze the discourse of sexual excess
      produced by Brazilian social thinking in the 1920s and 1930s and its dialog with
      the medical discourse at the time. Inspired by Foucault, it is within the field
      of the history of knowledge and is supported by sociology and medical documents
      from the period in question.Within the framework of the twentieth century re
      codification of the imagery of Brazilianness, the topic of sexual excess was
      revisited by local thinkers in the field of sociology and seen either as
      disturbing the national civilizing project, or as a trait that should be seen in
      a positive light because it permitted the cultural hybridization of its sources
      of identity. 

PMID- 25606720
TI  - On slaves and genes: "origins" and "processes" in genetic studies of the
      Brazilian population.
AB  - In this article I examine how contemporary geneticists investigating the history
      and configuration of the Brazilian population engage with other academic
      disciplines. To do so I use as a case study some articles published by
      geneticists researching the presence of hemoglobin S variants in Brazil, in which
      there is a clear pretension to contribute to the analysis of issues such as
      slavery or Brazil's ethnic identity. By contrasting these studies with
      contemporary works from history and the social science, the explanatory
      centrality of "origin" in the genetic studies analyzed is problematized, as is
      the lack of interaction with the epistemological characteristics of other areas
      of knowledge. 

PMID- 25606721
TI  - The body of the nation: government positions on physical education during the
      Brazilian monarchy.
AB  - In association with its nation building projects, the imperial government in
      Brazil under monarchic rule took some concrete actions based on proposals for
      physical education. The aim of this article is to investigate the meanings and
      significations attributed to this subject in the legislation and the annual
      reports issued by the Ministry of Business of the Empire (1831-1889), giving
      special attention to Rio de Janeiro. The approach to the subject in the sources
      researched demonstrates that the views of physical education took shape through a
      web of ideas that associated moral, health and civilization conceptions, in a bid
      to deal with the concrete circumstances of a newly independent peripheral nation
      with a bureaucratic structure in the process of formation. 

PMID- 25606722
TI  - Irritable heart syndrome in Anglo-American medical thought at the end of the
      nineteenth century.
AB  - This paper examines the characteristics and the conditions for the emergence of
      the nosological category known as irritable heart syndrome to be found in Anglo
      American medical literature in the second half of the nineteenth century. In the
      context of the American Civil War, it looks at some of the socio-historical
      elements, which comprised the medical care given to certain cardiac symptoms
      shown by soldiers. It emphasizes the moral values influencing the medical
      attitudes of military physicians towards symptoms of fear experienced by
      combatants, as well as the British and American etiological theories, which
      contributed to the nosological characterization of the suffering of soldiers
      afflicted with palpitations. Finally, it offers a brief analysis of the specific
      nature of the medical category known as irritable heart syndrome in the light of
      the categories of fear described by current psychiatric nosology. 

PMID- 25606723
TI  - Boys in white: a classic of qualitative research turns 50.
AB  - This article analyzes Boys in white: student culture in medical schoolby Howard
      S. Becker, Blanche Geer, Everett C. Hughes and Anselm Strauss, considered a model
      of qualitative research in sociology. The analysis investigates the trajectories
      of the authors, the book, qualitative analysis, and the medical students,
      emphasizing their importance in the origins of medical sociology and the
      sociology of medical education. In the trajectory of the authors, bibliographical
      information is given. The trajectory of qualitative research focuses on how this
      methodology influences the construction of the field. The investigation of the
      students' trajectory shows how they progress through their first years at medical
      school to build their own student culture. 

PMID- 25606724
TI  - [Another Dante's inferno in a gold mine during the Vargas era: Nova Lima, Minas
      Gerais].
AB  - This article analyzes the control strategies in place at Morro Velho mine in the
      Brazilian state of Minas Gerais, and the changes after the implementation of
      labor legislation during the Vargas administration. The diseases common amongst
      mine workers, silicosis and arsenicosis, are investigated through statements
      given by former miners and a book by an anonymous author that discusses the
      diseases and the power relations between employers and employees, identifying the
      limitations of the legislation and the workers' struggles. The book presents a
      striking story of how for many years the British company side-stepped laws such
      as the insalubrity premium, a right which other mining companies, not only of
      British ownership, flouted and still flout in different parts of the world. 

PMID- 25606725
TI  - [Notes on the Chain of Being and the place of blacks in eighteenth-century
      European natural philosophy].
AB  - This examination of academic works produced by eighteenth-century natural
      philosophers discusses some recurring ideas about the Chain of Being. To this
      end, the article analyzes the relations between natural philosophy and theology
      during the period. It also re-evaluates some elements of the Chain of Being
      through an exploration of authors who addressed the topic in their writings.
      Lastly, it identifies a specific element within eighteenth-century discussions of
      scala naturae, to wit, the various and not always convergent ideas about whether
      there are differences between humans based on specific characteristics and,
      consequently, about the places they occupy in the chain of being. 

PMID- 25606726
TI  - [Minas Gerais Radium Institute: at the forefront of radiotherapy in Brazil, 1923
      1935].
AB  - This article proposes to study the first 12 years of the Minas Gerais Radium
      Institute, founded in 1922. Its work in the fight against cancer in Brazil,
      albeit still little known, is coming to light as its institutional documents are
      studied. A database has been prepared using information from its patient
      register, based on which statistical analyses have been done to identify the
      types of cancer and treatments available there between 1923 and 1935. This
      register is one of five recently unearthed at the Medicine Memory Center of the
      Universidade Federal de Minas Gerais. Through them, the earliest experiments in
      radiotherapy in Brazil can be reconstituted, and its development and the
      influence of this model hospital can be mapped out. 

PMID- 25606727
TI  - [Federal university hospitals and their institutional missions in the past and
      present].
AB  - The definition of a university hospital presupposes the integration of teaching,
      research and healthcare. Considering these activities constituent parts of
      university hospitals' missions, an analysis was made from the administrators'
      viewpoint of their place in these institutions at their founding and in the
      present day. Semi-structured interviews were held with the administrators of 13
      of the 31 general hospitals run at Brazil's federal universities. Parallel to
      this, official information was gathered and analyzed from the 31 university
      hospitals' websites. Using a content analysis technique, it was found that
      although most of the university hospitals state that research is one of their
      missions, alongside teaching and healthcare, in practice teaching and healthcare
      take precedence. 

PMID- 25606728
TI  - [Between the country and the laboratory: the dynamics of the production of
      knowledge at the Menopause Outpatients Clinic at Caism, Unicamp].
AB  - This study investigates the practices involved in the production of knowledge
      about menopause at Caism, Unicamp, a reference center for public policies for
      women's health. Gynecological appointments and psychological support meetings
      were observed, and women and doctors were interviewed in order to identify what
      discourse circulates there and how different actors are brought in to ensure that
      the knowledge produced attains credibility and "travels" beyond the boundaries of
      the teaching hospital to become "universal". The analysis is based on localized
      studies aligned with social studies of science and technology. 

PMID- 25606729
TI  - [Anatomy and the teaching of anatomy in Brazil: the Boverian school].
AB  - There is little scholarly research on the history, teaching and research of human
      anatomy in Brazil. A broader vision of the progress of anatomy under different
      circumstances in the country is virtually non-existent, leaving researchers keen
      to study the subject insecure. This is compounded by the fact that the data
      available are not always reliable. This text retraces the development of the
      discipline of anatomy and its research and education in Brazil in general and Sao
      Paulo state in particular, which can largely be reduced to the action of the self
      proclaimed Boverian school of anatomy, founded by Italian physician Alfonso
      Bovero at the same time as the Medical Faculty of the University of Sao Paulo. 

PMID- 25606730
TI  - [The motives for hospitalization at Adauto Botelho Hospital (Cariacica, ES) in
      the second half of the twentieth century].
AB  - This paper discusses the procedures for referring patients to Adauto Botelho
      Hospital, in Cariacica, Espirito Santo state, Brazil. The research is based on
      the medical records since its inauguration in 1954 and statements by people who
      worked there in the second half of the twentieth century. One hundred and two
      records were analyzed and four people were interviewed. The records revealed the
      active involvement of the Chief of Police in hospitalizations. The interviews
      corroborate this, while also showing the long duration of the hospitalizations.
      The tone of the paper is set by the life stories of the people hospitalized
      there. The conclusion is that this hospital served not so much for treatment as
      for confinement. 

PMID- 25606731
TI  - [Geography, health and urban development in Sao Paulo state at the turn of the
      twentieth century: Domingos Jaguaribe and the construction of the Climate Resort
      of Campos do Jordao].
AB  - The resort towns created in the early 1900s are prime objects for studying the
      relationship between public health policies and urban and social development.
      This article analyzes the social and institutional vectors involved in the
      creation of the resort town of Campos do Jordao from the perspective of the
      career and works of physician, geographer and businessman Domingos Nogueira
      Jaguaribe Filho. Geographical studies, medical knowledge and the precepts of
      urbanization combined with private and development interests in the symbolism and
      concrete manifestation of the "Brazilian Switzerland". 

PMID- 25606733
TI  - [The socialization of medicine in the era of Sao Paulo Governor Adhemar de
      Barros].
AB  - The article analyzes how the process of the professionalization of physicians in
      Sao Paulo related to healthcare policy under the administration of Sao Paulo
      governor Adhemar de Barros (1947-1951) during a period of broad change in the
      realm of health known by Sao Paulo physicians as the "socialization of medicine."
      Medical professionalism confronted certain ambivalences under this populist
      administration, including doctors' struggle to achieve pay equal to that of state
      public attorneys; the establishment of a state health department; and some
      contradictory ties between the area of health under Adhemar and the professional
      ideology and organization of medicine in Sao Paulo. The article undertakes a more
      in-depth analysis of the ideological manifestations of important leaders in the
      state's medical community. 

PMID- 25606732
TI  - [Anti-aging medicine: notes on a socio-technical controversy].
AB  - After some decades of struggle, geriatrics and gerontology have become the
      legitimate sciences of aging. Today, their status is being questioned. In its
      short history, anti-aging medicine has taken root as a medical practice that
      questions how to address biological aging. In so doing, all medicine is
      questioned. Here, we explore in particular how this controversy is structured
      around the founding principles of the sciences of aging. Is there any basis for
      these questionings? How have they been treated by those who have received them?
      Taking a socio-technical viewpoint, it is worth considering that for
      geriatricians and gerontologists, the need to criticize anti-aging medicine also
      raises some important reflections about how the sciences of aging address their
      subject. 

PMID- 25606734
TI  - Cleansing the world of the germ of laziness: hygiene, sanitation, and the
      Javanese population in Suriname.
AB  - In 1915 the Rockefeller Foundation took its hookworm eradication campaign to
      Suriname, but was soon disappointed because of opposition from its main target
      group: the Javanese. Moreover, authorities and planters objected to the
      construction of latrines because of the costs and their belief that the Javanese
      were "unhygienic". In describing the labor migration from Java to Suriname, I
      show that this "lack of hygiene" was closely related to the system's
      organization. I argue that uncleanliness was the consequence of harmful socio
      economic and ecological conditions. Secondly I suggest that even though the
      Foundation did not manage to cleanse Suriname of hookworm, its educational
      efforts, its emphasis on prevention, and its training of local health workers
      probably had more impact than Rockefeller officials thought. 

PMID- 25606735
TI  - [Looking beyond the campaign to eradicate ancylostomiasis: the diary of the
      American physician Alan Gregg].
AB  - Between 1916 and 1923, the Federal District and 11 Brazilian states entered into
      cooperation agreements with the International Health Board of the Rockefeller
      Foundation to combat a rural endemic disease, namely ancylostomiasis. This paper
      presents the diary of Alan Gregg, one of the American physicians who worked in
      Brazil from 1919 to 1922. An interesting source to discuss issues relating to the
      history of public health in Brazil, in addition to information about the
      activities to combat ancylostomiasis developed by the Rockefeller Foundation in
      the country, the diary of the physician presents his impressions concerning
      nature, culture, politics and society in Brazil. In the diary excerpts presented
      here, however, aspects related to the professional activities performed by Gregg
      are prioritized. 

PMID- 25606736
TI  - [The social context of the birth control debate in Colombia in the 1960s and
      1970s: politics, medicine and society].
AB  - The article seeks to present the necessary context and a preliminary approach to
      understanding and addressing the birth control debate in Colombia in the 1960s
      and 1970s. It covers the main conflicting positions during that period and the
      discourses and logics permeating the arrival of North American family planning
      programs to Latin America as a form of political control of revolutionary
      movements. 

PMID- 25606737
TI  - [Decriminalizing traditional Andean medicine: an interview with Walter Alvarez
      Quispe].
AB  - Walter Alvarez Quispe, a Kallawaya healer and biomedical practitioner
      specializing in general surgery and gynecology, presents the struggle of
      traditional and alternative healers to get their Andean medical systems
      depenalized between 1960 and 1990. Bolivia was the first country in Latin America
      and the Caribbean to decriminalize traditional medicine before the proposals of
      the International Conference on Primary Health Care (Alma-Ata, 1978). The data
      provided by the interviewee show that the successes achieved, mainly by the
      Kallawayas, stem from their own independent initiative. These victories are not
      the result of official policies of interculturality in healthcare, although the
      successes achieved tend to be ascribed to them. 

PMID- 25606742
TI  - Lessons from Washington State's Medical Home Payment Pilot: What It Will Take to
      Change American Health Care.
AB  - The Washington State Multi-Payer Medical Home Reimbursement Pilot (Pilot) tested
      a payment method for the patient-centered medical home (PCMH) model intended to
      reduce avoidable emergency department (ED) and hospitalization rates. Very little
      is known about the primary care clinic (clinic) experience with various payment
      methods designed for the medical home model. The objective was to elicit and
      describe the primary care clinic experience among various medical groups in
      Washington State's payment Pilot. This was a qualitative analysis of semi
      structured interviews conducted in January 2014 to identify enabling features (or
      "facilitators") as well as barriers to successful implementation of PCMH in this
      multi-payer pilot. Participants were clinical and administrative staff of Pilot
      clinics representing various types of health systems under 8 parent organizations
      across Washington State. Pilot clinics across Washington State chose evidence
      based population health strategies to achieve Pilot targets. Pilot clinics
      encountered more barriers than facilitators when implementing strategies. A key
      facilitator was having timely access to ED and hospital clinical data. A common
      barrier was the cost of infrastructure development to implement strategies. Other
      barriers included lack of data to guide interventions and insufficient payment
      for care management and quality improvement work. It will take more than just
      primary care transformation to improve health outcomes--a significant
      transformation in data collection, reporting and payment needs to match the
      change occurring in clinics.

PMID- 25606743
TI  - Accurate and automated image segmentation of 3D optical coherence tomography data
      suffering from low signal-to-noise levels.
AB  - Optical coherence tomography (OCT) has proven to be a useful tool for
      investigating internal structures in ceramic tapes, and the technique is expected
      to be important for roll-to-roll manufacturing. However, because of high
      scattering in ceramic materials, noise and speckles deteriorate the image
      quality, which makes automated quantitative measurements of internal interfaces
      difficult. To overcome this difficulty we present in this paper an innovative
      image analysis approach based on volumetric OCT data. The engine in the analysis
      is a 3D image processing and analysis algorithm. It is dedicated to boundary
      segmentation and dimensional measurement in volumetric OCT images, and offers
      high accuracy, efficiency, robustness, subpixel resolution, and a fully automated
      operation. The method relies on the correlation property of a physical interface
      and effectively eliminates pixels caused by noise and speckles. The remaining
      pixels being stored are the ones confirmed to be related to the target
      interfaces. Segmentation of tilted and curved internal interfaces separated by
      ~10  MUm in the Z direction is demonstrated. The algorithm also extracts full
      field top-view intensity maps of the target interfaces for high-accuracy
      measurements in the X and Y directions. The methodology developed here may also
      be adopted in other similar 3D imaging and measurement technologies, e.g.,
      ultrasound imaging, and for various materials. 

PMID- 25606744
TI  - Bidirectional reflectance distribution function measurements and analysis of
      retroreflective materials.
AB  - We compare the performance of various analytical retroreflecting bidirectional
      reflectance distribution function (BRDF) models to assess how they reproduce
      accurately measured data of retroreflecting materials. We introduce a new
      parametrization, the back vector parametrization, to analyze retroreflecting
      data, and we show that this parametrization better preserves the isotropy of
      data. Furthermore, we update existing BRDF models to improve the representation
      of retroreflective data. 

PMID- 25606745
TI  - Ellipse fitting for interferometry. Part 1: static methods.
AB  - We compare a number of different methods for fitting an ellipse to a static set
      of measured data points, specifically considering their suitability for
      interferometric application. We suggest an improved distance approximation for
      least-square geometric fitting and alternative normalizations for linear
      algebraic fitting. Of the methods considered, an algebraic fit using a data
      dependent normalization has both the least bias in phase and amplitude estimation
      and the greatest robustness against uneven distribution of data. 

PMID- 25606746
TI  - Comparison of focal properties of square-channel and meridional lobster-eye
      lenses.
AB  - The lobster-eye telescope with square cross-section channels has been suggested
      as a possible candidate for a wide-field-of-view x-ray all-sky monitor. However,
      due to the difficult construction, especially with metals, variations of lobster
      eye lenses have been proposed as possible alternatives. This work is a
      computational comparison of the focal properties of one variant, the meridional
      lens, with the square-channel lens. For both types of lens, the efficiency of
      focusing for imaged photons as well as the point-spread function in one dimension
      is studied for collimated sources. 

PMID- 25606747
TI  - One-dimensional voting scheme for circle and arc detection.
AB  - Circle detection is an important issue that has not been perfectly solved in
      automated image analysis to date. It is traditionally carried out via pixel-based
      3D voting algorithms, involving tremendous computation and requiring huge storage
      space with questionable accuracy. In this report, a novel edge-section-based 1D
      voting algorithm is developed in circle detection to improve the detection rate
      and precision. Based on experiments with simulated image data and a ground-tested
      standard dataset, the novel scheme significantly outperformed all previous state
      of-the-art schemes in detection rate and precision, and was comparable to the
      state of the art in processing speed. 

PMID- 25606748
TI  - Effect of beam size, finite number of lines, and rotational misalignment on
      coupled subwavelength gratings.
AB  - The effects of beam size, number of lines, and rotational misalignment on coupled
      subwavelength gratings (CSWGs) were investigated in this paper using optical
      modeling. Period and thickness of the gratings were optimized for maximum
      evanescent wave coupling efficiency at a wavelength of 650 nm. The size of the
      input light beam and the number of grating lines were established for discernible
      transmission of higher diffraction orders, and the half-width at half-maximum for
      minimum noise was determined. A rotation of the far-field pattern, due to milling
      one grating on a fiber facet, was calculated and confirmed by simulations. These
      parameters will be included in a method using CSWGs for electronic chip security.

PMID- 25606749
TI  - Feature-based filter design for resolution enhancement of known features in
      microscopy.
AB  - We present a new feature-based design concept for filter design in which a filter
      is designed specifically to image a known feature with dimensions lower than the
      optical resolution of the system. Unlike the conventional filter design based on
      focal spot engineering, we use the complete response of the microscope to form a
      resolution factor and consider minimizing the resolution factor as the design
      goal. We consider three design goals (i.e., resolution factors) based on the
      system response and show that a feature matching approach is more suitable in
      practice. It is shown that a three-bar pattern and grid of square dots of
      critical dimension, 0.08lambda, can be resolved using a simple two-layer feature
      based filter designed for radially polarized illumination in aplanatic solid
      immersion lens microscopy. An example that requires a more complex filter is also
      shown. Applicability of the concept of feature-based filter design in diverse
      microscopy scenarios is discussed as well. 

PMID- 25606750
TI  - Electromagnetic subsurface prospecting by a fully nonlinear multifocusing inexact
      Newton method.
AB  - An electromagnetic inverse scattering procedure for the reconstruction of shallow
      buried objects in a homogeneous half-space is proposed. The approach is based on
      the numerical solution of the integral equations that model inverse scattering
      relationships, and it extends to strong scatterers the imaging capabilities of a
      previously proposed approach relying on approximated formulations. The inversion
      is based on the synergic application of a multifocusing strategy based on the
      iterative multiscaling approach along with an efficient regularization scheme
      based on the inexact Newton method. Numerical results corroborate the
      mathematical description to assess capabilities and current limitations of the
      proposed fully nonlinear technique. 

PMID- 25606751
TI  - Scattering of an electromagnetic plane wave by a homogeneous sphere made of an
      orthorhombic dielectric-magnetic material: erratum.
AB  - A correction is given for an equation in [J. Opt. Soc. Am. A31, 89-100
      (2014)10.1364/JOSAA.31.000089JOAOD61084-7529]. 

PMID- 25606752
TI  - Two-dimensional nonseparable linear canonical transform: sampling theorem and
      unitary discretization.
AB  - The two-dimensional (2D) nonseparable linear canonical transform (NS-LCT) is a
      unitary, linear integral transform that relates the input and output
      monochromatic, paraxial scalar wave fields of optical systems characterized by a
      4*4 ray tracing matrix. In addition to the obvious generalizations of the 1D LCT
      (which are referred to as separable), the 2D-NS-LCT can represent a variety of
      nonaxially symmetric optical systems including the gyrator transform and image
      rotation. Unlike the 1D LCT, the numerical approximation of the 2D-NS-LCT has not
      yet received extensive attention in the literature. In this paper, (1) we develop
      a sampling theorem for the general 2D-NS-LCT which generalizes previously
      published sampling theorems for the 1D case and (2) we determine which sampling
      rates may be chosen to ensure that the obvious discrete transform is unitary. 

PMID- 25606753
TI  - Double image in far peripheral vision of pseudophakic eye as source of negative
      dysphotopsia.
AB  - Some intraocular lens (IOL) patients report seeing "dark shadows" at visual
      angles that are larger than 60 degrees -70 degrees . Raytrace models of the
      pseudophakic eye show that light starts to miss the IOL at large visual angles
      because the implant diameter of about 6 mm is much smaller than the natural
      crystalline lens diameter of 9.5 mm. This light forms a second displaced image on
      the peripheral retina. To evaluate the appearance of the image, raytrace software
      was used to image an illuminated window onto the highly curved retina, and a
      method was developed to project the image back to object space for evaluation on
      a flat surface. Only a single schematic eye was evaluated monochromatically and
      the low resolution of the peripheral retina was not modeled, but the simulated
      images depict a shadow-like phenomenon at similar visual angles to reports of
      "negative dysphotopsia." 

PMID- 25606754
TI  - Theoretical performance model for single image depth from defocus.
AB  - In this paper we present a performance model for depth estimation using single
      image depth from defocus (SIDFD). Our model is based on an original expression of
      the Cramer-Rao bound (CRB) in this context. We show that this model is consistent
      with the expected behavior of SIDFD. We then study the influence on the
      performance of the optical parameters of a conventional camera such as the focal
      length, the aperture, and the position of the in-focus plane (IFP). We derive an
      approximate analytical expression of the CRB away from the IFP, and we propose an
      interpretation of the SIDFD performance in this domain. Finally, we illustrate
      the predictive capacity of our performance model on experimental data comparing
      several settings of a consumer camera. 

PMID- 25606755
TI  - QBRIX: a quantile-based approach to retinex.
AB  - In this paper, we introduce a novel probabilistic version of retinex. It is based
      on a probabilistic formalization of the random spray retinex sampling and
      contributes to the investigation of the spatial properties of the model. Various
      versions available of the retinex algorithm are characterized by different
      procedures for exploring the image content (so as to obtain, for each pixel, a
      reference white value), then used to rescale the pixel lightness. Here we propose
      an alternative procedure, which computes the reference white value from the
      percentile values of the pixel population. We formalize two versions of the
      algorithm: one with global and one with local behavior, characterized by
      different computational costs. 

PMID- 25606756
TI  - Two-dimensional complex source point solutions: application to propagationally
      invariant beams, optical fiber modes, planar waveguides, and plasmonic devices.
AB  - Highly convergent beam modes in two dimensions are considered based on rigorous
      solutions of the scalar wave (Helmholtz) equation, using the complex source point
      formalism. The modes are applicable to planar waveguide or surface plasmonic
      structures and nearly concentric microcavity resonator modes in two dimensions. A
      novel solution is that of a vortex beam, where the direction of propagation is in
      the plane of the vortex. The modes also can be used as a basis for the cross
      section of propagationally invariant beams in three dimensions and bow-tie-shaped
      optical fiber modes. 

PMID- 25606757
TI  - Cramer-Rao bounds in functional form: theory and application to passive optical
      ranging.
AB  - A functional approach to the multivariate statistical model of a generalized
      incoherent passive optical ranging and imaging system with a CCD sensor is
      proposed. This approach implies that a large number of discrete, statistically
      independent, random data (pixel readouts) can be approximated by a continuous
      random function. Thus, the joint probability density function (PDF) takes a
      functional form; the statistical averages of the infinite-variate PDF and the
      Fisher information become functional integrals that can be treated analytically
      in the Gaussian approximation. The Cramer-Rao bounds on estimator-error variances
      are obtained for the scalar and functional deterministic parameters of the model.
      An approximate expression is derived for the PDF of the sum of independent
      Gaussian and Poisson random variables using the steepest-descent method, and the
      resulting PDF is shown to be asymptotically Gaussian. As an illustration, we
      apply the developed approach to a passive optical rangefinder with chiral
      wavefront coding. Numerical and experimental examples are presented. 

PMID- 25606758
TI  - Adaptive deformation correction of depth from defocus for object reconstruction.
AB  - The accuracy of three-dimensional object reconstruction using depth from defocus
      (DfD) can be severely reduced by elliptical lens deformation. This paper presents
      two correction methods, correction by deformation cancellation (CDC) and
      correction by least squares fit (CLSF). CDC works by subtracting the current
      deformed depth value by a prestored deformed value, and CLSF by mapping the
      deformed values to the expected values. Each method is followed by a smoothing
      algorithm to address the low-texture problem of DfD. Experiments using four DfD
      methods on real images show that the proposed methods effectively and efficiently
      eliminate the deformation. 

PMID- 25606760
TI  - Cutoff due to pointwise degradations in color images.
AB  - Many studies analyze resolution limits in single-channel, pan-chromatic systems.
      However, color imaging is popular. Thus, there is a need for its modeling in
      terms of resolving capacity under noise. This work analyzes the probability of
      resolving details as a function of spatial frequency in color imaging. The
      analysis introduces theoretical bounds for performance, using optimal linear
      filtering and fusion operations. The work focuses on resolution loss caused
      strictly by noise, without the presence of imaging blur. It applies to full-field
      color systems, which do not compromise resolution by spatial multiplexing. The
      framework allows us to assess and optimize the ability of an imaging system to
      distinguish an object of given size and color under image noise. 

PMID- 25606759
TI  - Noise characterization of supercontinuum sources for low-coherence interferometry
      applications.
AB  - We examine the noise properties of supercontinuum light sources when used in low
      coherence interferometry applications. The first application is a multiple
      scattering low-coherence interferometry (ms2/LCI) system, where high power and
      long image acquisition times are required to image deep into tissue. For this
      system, we compare the noise characteristics of two supercontinuum sources from
      different suppliers. Both sources have long-term drift that limits the amount of
      time over which signal averaging is advantageous for reducing noise. The second
      application is a high-resolution optical coherence tomography system, where
      broadband light is needed for high axial resolution. For this system, we compare
      the noise performance of the two supercontinuum sources and a light source based
      on four superluminescent diodes (SLD) using imaging contrast as a comparative
      metric. We find that the NKT SuperK has superior noise performance compared with
      the Fianium SC-450-4, but neither meets the performance of the SLD. 

PMID- 25606761
TI  - Foucault test: shadowgram modeling from the physical theory for quantitative
      evaluations.
AB  - The physical theory of the Foucault test has been investigated to represent the
      complex amplitude and irradiance of the shadowgram in terms of the wavefront
      error; however, most of the studies have limited the treatment for the particular
      case of nearly diffraction-limited optical devices (i.e., aberrations smaller
      than the wavelength). In this paper we discard this restriction, and in order to
      show a more precise interpretation from the physical theory we derive expressions
      for the complex amplitude and the irradiance over an optical device with larger
      aberrations. To the best of our knowledge, it is the first time an expression is
      obtained in closed form. As will be seen, the result of this derivation is
      obtained using some properties of the Hilbert transform that permit representing
      the irradiance in a simple form in terms of the partial derivatives of the
      wavefront error. Additionally, we briefly describe from this point of view a
      methodology for the quantitative analysis of the test. 

PMID- 25606762
TI  - Holographic laser Doppler imaging of microvascular blood flow.
AB  - We report on local superficial blood flow monitoring in biological tissue from
      laser Doppler holographic imaging. In time-averaging recording conditions,
      holography acts as a narrowband bandpass filter, which, combined with a frequency
      shifted reference beam, permits frequency-selective imaging in the radio
      frequency range. These Doppler images are acquired with an off-axis Mach-Zehnder
      interferometer. Microvascular hemodynamic components mapping is performed in the
      cerebral cortex of the mouse and the eye fundus of the rat with near-infrared
      laser light without any exogenous marker. These measures are made from a basic
      inverse-method analysis of local first-order optical fluctuation spectra at low
      radio frequencies, from 0 Hz to 100 kHz. Local quadratic velocity is derived from
      Doppler broadenings induced by fluid flows, with elementary diffusing wave
      spectroscopy formalism in backscattering configuration. We demonstrate quadratic
      mean velocity assessment in the 0.1-10 mm/s range in vitro and imaging of
      superficial blood perfusion with a spatial resolution of about 10 micrometers in
      rodent models of cortical and retinal blood flow. 

PMID- 25606763
TI  - From a nondepolarizing Mueller matrix to a depolarizing Mueller matrix.
AB  - The depolarizing properties of a generic Mueller matrix are synthesized from a
      corresponding nondepolarizing reference Mueller matrix, which is appropriately
      factorized and transformed by sequentially adjusting the values of three indices
      of polarimetric purity (IPP) [Opt. Commun.284, 38 (2011)OPCOB80030-4018]. This
      procedure allows generating type-I and type-II arbitrary Mueller matrices from an
      adequate choice of the reference Mueller matrix and, by reducing, in a consistent
      way, the starting 1-valued IPP. This synthesis procedure also provides better
      understanding of the sources and structure of depolarization. 

PMID- 25606764
TI  - Circular Bessel statistics: derivation and application to wave propagation in
      random media.
AB  - We present a family of circular Bessel probability density functions that are
      capable of describing the intensity, amplitude, and field statistics of waves in
      any random medium, with only the assumption of circularity. The well-known zero
      mean circular Gaussian statistics break down in the Anderson localization and the
      weakly scattering regimes, where the field can no longer be regarded as the sum
      of a multitude of independent random phasors. We find that in such scenarios
      circular Bessel statistics apply because the field can be modeled as a random
      phasor sum with a random number of contributing phasors. The validity of our
      density functions is verified through numerical simulations of electromagnetic
      waves propagating in 2D random media. Having a set of density functions that work
      in all scattering regimes provides a framework for modeling wave propagation in
      random media, facilitating random media characterization, imaging in and through
      scatter, and random laser design. 

PMID- 25606765
TI  - Degree of polarization of a tightly focused, partially coherent anomalous hollow
      beam.
AB  - By using the Richards-Wolf vector diffraction theory, the formulas of the
      propagation of a linearly polarized, partially coherent anomalous hollow beam
      (AHB) through a high numerical aperture (NA) thin lens are derived. The tight
      focusing properties of a partially coherent AHB, including the degree of
      polarization, the intensity distribution, and the degree of coherence, are
      studied in detail. It is found that the focusing properties of a partially
      coherent AHB are closely determined by the initial coherence, initial beam
      parameters, and NA of the thin lens. However, no matter how high the value of
      eccentricity, the initial beam will reduce to a Gaussian beam of quasi-circular
      symmetry at the focal plane. No matter the value of NA, the size of the beam will
      remain invariant, which is an interesting phenomenon, and the beam has good
      stability. The results may find application in optical trapping with a partially
      coherent field. 

PMID- 25606766
TI  - Manipulation of dielectric particles with nondiffracting parabolic beams.
AB  - The trapping and manipulation of microscopic particles embedded in the structure
      of nondiffracting parabolic beams is reported. The particles acquire orbital
      angular momentum and exhibit an open trajectory following the parabolic fringes
      of the beam. We observe an asymmetry in the terminal velocity of the particles
      caused by the counteracting gradient and scattering forces. 

PMID- 25606767
TI  - Anti-aliasing Wiener filtering for wave-front reconstruction in the spatial
      frequency domain for high-order astronomical adaptive-optics systems.
AB  - Computationally efficient wave-front reconstruction techniques for astronomical
      adaptive-optics (AO) systems have seen great development in the past decade.
      Algorithms developed in the spatial-frequency (Fourier) domain have gathered much
      attention, especially for high-contrast imaging systems. In this paper we present
      the Wiener filter (resulting in the maximization of the Strehl ratio) and further
      develop formulae for the anti-aliasing (AA) Wiener filter that optimally takes
      into account high-order wave-front terms folded in-band during the sensing (i.e.,
      discrete sampling) process. We employ a continuous spatial-frequency
      representation for the forward measurement operators and derive the Wiener filter
      when aliasing is explicitly taken into account. We further investigate and
      compare to classical estimates using least-squares filters the reconstructed wave
      front, measurement noise, and aliasing propagation coefficients as a function of
      the system order. Regarding high-contrast systems, we provide achievable
      performance results as a function of an ensemble of forward models for the Shack
      Hartmann wave-front sensor (using sparse and nonsparse representations) and
      compute point-spread-function raw intensities. We find that for a 32*32 single
      conjugated AOs system the aliasing propagation coefficient is roughly 60% of the
      least-squares filters, whereas the noise propagation is around 80%. Contrast
      improvements of factors of up to 2 are achievable across the field in the H band.
      For current and next-generation high-contrast imagers, despite better aliasing
      mitigation, AA Wiener filtering cannot be used as a standalone method and must
      therefore be used in combination with optical spatial filters deployed before
      image formation actually takes place. 

PMID- 25606768
TI  - Two-flux transfer matrix model for predicting the reflectance and transmittance
      of duplex halftone prints.
AB  - We introduce a model allowing convenient calculation of the spectral reflectance
      and transmittance of duplex prints. It is based on flux transfer matrices and
      enables retrieving classical Kubelka-Munk formulas, as well as extended formulas
      for nonsymmetric layers. By making different assumptions on the flux transfers,
      we obtain two predictive models for the duplex halftone prints: the "duplex
      Clapper-Yule model," which is an extension of the classical Clapper-Yule model,
      and the "duplex primary reflectance-transmittance model." The two models can be
      calibrated from either reflectance or transmittance measurements; only the second
      model can be calibrated from both measurements, thus giving optimal accuracy for
      both reflectance and transmittance predictions. The conceptual differences
      between the two models are deeply analyzed, as well as their advantages and
      drawbacks in terms of calibration. According to the test carried out in this
      study with paper printed in inkjet, their predictive performances are good
      provided appropriate calibration options are selected. 

PMID- 25606769
TI  - Equivalence relations and symmetries for laboratory, LIDAR, and planetary Mueller
      matrix scattering geometries.
AB  - Symmetry relationships for optical observations of matter generally fall into
      several common scattering geometries. The "planetary" configuration is preferred
      by observers of extraterrestrial planets, "laboratory" observations are performed
      in the biomedical research field, and the LIDAR configuration is preferred by
      those using lasers to probe optical properties of horizontal surfaces with mirror
      or axial symmetry. This paper begins with the Stokes matrix formalism and uses
      symmetries of Muller matrix scattering to establish links among the mathematical
      symmetries of each geometric configuration. We finish the paper by identifying
      and correcting an influential misapplication of rotational scattering matrices in
      the literature. The corrected equation should find wide application in models of
      the LIDAR scattering process. 

PMID- 25606770
TI  - Standard deviation of luminance distribution affects lightness and pupillary
      response.
AB  - We examined whether the standard deviation (SD) of luminance distribution serves
      as information of illumination. We measured the lightness of a patch presented in
      the center of a scrambled-dot pattern while manipulating the SD of the luminance
      distribution. Results showed that lightness decreased as the SD of the surround
      stimulus increased. We also measured pupil diameter while viewing a similar
      stimulus. The pupil diameter decreased as the SD of luminance distribution of the
      stimuli increased. We confirmed that these results were not obtained because of
      the increase of the highest luminance in the stimulus. Furthermore, results of
      field measurements revealed a correlation between the SD of luminance
      distribution and illuminance in natural scenes. These results indicated that the
      visual system refers to the SD of the luminance distribution in the visual
      stimulus to estimate the scene illumination. 

PMID- 25606771
TI  - Robust block sparse discriminative classification framework.
AB  - In this paper, a block sparse discriminative classification framework (BSDC) is
      proposed under the assumption that a block or group structure exists in sparse
      coefficients on classification. First, we propose a block discriminative
      dictionary-learning (BDDL) algorithm, which learns class-specific subdictionaries
      and forces the sparse coefficients to be block sparse. An efficient gradient
      based optimization strategy of BDDL also is developed, and the block sparse
      constraint of the sparse coefficient leads to a least-squares solution of nonzero
      entries in the sparse coding stage of dictionary learning. Second, to take
      advantage of the structures when a new test sample is given, conventional sparse
      coding algorithms are discarded, and structured sparse coding methods are
      adopted. Experiments validate the effectiveness of the proposed framework in face
      recognition and texture classification. We also show that BSDC is robust to
      noise. 

PMID- 25606772
TI  - Inverse source in the presence of a reflecting plane for the strip case.
AB  - In this paper the inverse source problem in the presence of a reflecting plane is
      dealt with for a two-dimensional configuration and bounded rectilinear strip
      sources. The cases of both orthogonal and parallel (to the reflecting plane)
      sources are considered. Analytical arguments are developed to estimate the
      singular value decomposition of the pertinent radiation operator. This allows
      highlighting of the role played by the reflecting plane in the so-called number
      of degrees of freedom of the radiated field as well as in the achievable
      resolution while reconstructing the unknown sources. 

PMID- 25606773
TI  - Enforcing symmetries in boundary element formulation of plasmonic and second
      harmonic scattering problems.
AB  - The study of metal nanoparticles and metamaterials has increased the demand for
      accurate and efficient numerical methods for solving electromagnetic scattering
      problems. The boundary element method, and especially its Poggio-Miller-Chang
      Harrington-Wu-Tsai (PMCHWT) formulation, has received growing interest lately due
      to its accuracy and stability at plasmon resonance conditions. Consequently, this
      formulation has been used to model second-harmonic generation (SHG) in plasmonic
      nanoparticles, which is an area of increasing importance. Many nanostructures
      exhibit geometrical symmetries, whose identification is often crucial for the
      qualitative understanding of SHG. In this work, we present the theory and details
      to take advantage of these symmetries in the PMCHWT formulation. We show that,
      importantly, the symmetry of the medium can be exploited even though the
      excitation source does not exhibit a well-defined symmetry. We estimate the
      obtainable computational benefits and apply the method to the study of the linear
      and second-order nonlinear properties of multiply split gold ring resonators. 

PMID- 25606774
TI  - Robust and efficient inverse mask synthesis with basis function representation.
AB  - Mask optimization is essential in the resolution scaling of optical lithography
      due to its strong ability to overcome the optical proximity effect. However, it
      often demands extensive computation in solving the nonlinear optimization problem
      with a large number of variables. In this paper, we use a set of basis functions
      to represent the mask patterns, and incorporate this representation into the mask
      optimization at both the nominal plane and various defocus conditions. The
      representation coefficients are updated according to the gradient to the
      coefficients, which can be easily obtained from the gradient to the pixel
      variables. To ease the computation of the gradient, we use an adaptive method
      that divides the optimization into two steps, in which a small number of kernels
      is used as the first step, and more kernels are used for fine optimization.
      Simulations performed on two test patterns demonstrate that this method can
      improve the optimization efficiency by several times, and the optimized patterns
      have better manufacturability compared with regular pixel-based representation. 

PMID- 25606775
TI  - Efficient representation of mask transmittance functions for vectorial
      lithography simulations.
AB  - In this paper, a generalized method to efficiently represent the incident-angle
      dependent mask transmittance function (MTF) of a thick mask is proposed. This
      method expands the MTF into a series expansion, which consists of a set of
      predetermined basis functions weighted by a set of predetermined expansion
      coefficients. The predetermined basis functions are independent of the incident
      angles and thus may be computed offline and stored, while the expansion
      coefficients depend only on the incident angles and can be rapidly calculated
      online. Near-field and optical image simulations of thick masks have demonstrated
      the excellent accuracy and superior speed performance. 

PMID- 25606776
TI  - Illumination source optimization in optical lithography via derivative-free
      optimization.
AB  - Illumination source optimization (SO) in optical lithography is generally
      performed under a simulation model that does not consider critical effects such
      as the vectorial nature of light and mask topography. When a numerical aperture
      becomes large and the critical dimension reaches subwavelength, the prediction of
      this model generally fails; therefore, the previous works based on this model
      become inaccurate. In order to correctly compute SO, we first propose a new
      source pattern representation method that has moderate parameter variations but
      remains complete in solution space. Then we develop a derivative-free
      optimization (DFO) method to optimize these parameters under a rigorous
      simulation model. Unlike gradient-based techniques, DFO methods do not require a
      closed-form formulation of the model and are independent of the form of cost
      function. 

PMID- 25606777
TI  - Diffractive lens design for optimized focusing.
AB  - We utilized nonlinear optimization to design phase-only diffractive lenses that
      focus light to a spot, whose width is smaller than that dictated by the far-field
      diffraction limit. Although scalar-diffraction theory was utilized for the
      design, careful comparisons against rigorous finite-difference time-domain
      simulations confirm the superfocusing effect. We were able to design a lens with
      a focal spot size that is 25% smaller than that formed by a conventional lens of
      the same numerical aperture. An optimization strategy that allows one to design
      such lenses is clearly explained. Furthermore, we performed careful simulations
      to elucidate the effects of fabrication errors and defocus on the performance of
      such optimized lenses. Since these lenses are thin, binary, and planar, large
      uniform arrays could be readily fabricated enabling important applications in
      microscopy and lithography. 

PMID- 25606778
TI  - Gradient descent algorithm applied to wavefront retrieval from through-focus
      images by an extreme ultraviolet microscope with partially coherent source.
AB  - The wavefront retrieval by gradient descent algorithm that is typically applied
      to coherent or incoherent imaging is extended to retrieve a wavefront from a
      series of through-focus images by partially coherent illumination. For accurate
      retrieval, we modeled partial coherence as well as object transmittance into the
      gradient descent algorithm. However, this modeling increases the computation time
      due to the complexity of partially coherent imaging simulation that is repeatedly
      used in the optimization loop. To accelerate the computation, we incorporate not
      only the Fourier transform but also an eigenfunction decomposition of the image.
      As a demonstration, the extended algorithm is applied to retrieve a field
      dependent wavefront of a microscope operated at extreme ultraviolet wavelength
      (13.4 nm). The retrieved wavefront qualitatively matches the expected
      characteristics of the lens design. 

PMID- 25606779
TI  - Advances in lithography: introduction to the feature.
AB  - Optical projection lithography has been the key technology for the ongoing
      miniaturization in semiconductor devices over the past 40 years. This issue
      features original research covering mask and image modeling methods and
      computational techniques for various inverse problems in advanced lithography,
      including source and mask optimization, wavefront retrieval, and design of
      Fresnel lenses. 

PMID- 25606780
TI  - DNA charge transport within the cell.
AB  - The unique characteristics of DNA charge transport (CT) have prompted an
      examination of roles for this chemistry within a biological context. Not only can
      DNA CT facilitate long-range oxidative damage of DNA, but redox-active proteins
      can couple to the DNA base stack and participate in long-range redox reactions
      using DNA CT. DNA transcription factors with redox-active moieties such as SoxR
      and p53 can use DNA CT as a form of redox sensing. DNA CT chemistry also provides
      a means to monitor the integrity of the DNA, given the sensitivity of DNA CT to
      perturbations in base stacking as arise with mismatches and lesions. Enzymes that
      utilize this chemistry include an interesting and ever-growing class of DNA
      processing enzymes involved in DNA repair, replication, and transcription that
      have been found to contain 4Fe-4S clusters. DNA repair enzymes containing 4Fe-4S
      clusters, that include endonuclease III (EndoIII), MutY, and DinG from bacteria,
      as well as XPD from archaea, have been shown to be redox-active when bound to
      DNA, share a DNA-bound redox potential, and can be reduced and oxidized at long
      range via DNA CT. Interactions between DNA and these proteins in solution, in
      addition to genetics experiments within Escherichia coli, suggest that DNA
      mediated CT can be used as a means of cooperative signaling among DNA repair
      proteins that contain 4Fe-4S clusters as a first step in finding DNA damage, even
      within cells. On the basis of these data, we can consider also how DNA-mediated
      CT may be used as a means of signaling to coordinate DNA processing across the
      genome. 

PMID- 25606781
TI  - CD27low natural killer cells prolong allograft survival in mice by controlling
      alloreactive CD8+ T cells in a T-bet-dependent manner.
AB  - BACKGROUND: Natural killer (NK) cells play a dichotomous role in alloimmune
      responses because they are known to promote both allograft survival and
      rejection. The aim of this study was to investigate the role of functionally
      distinct NK cell subsets in alloimmunity with the hypothesis that this dichotomy
      is explained by the functional heterogeneity of distinct NK cell subsets.
      METHODS: Because T-bet controls thematuration of NK cells from CD27high to
      terminally differentiated CD27low NK cells, we used Rag-/-T-bet-/- mice that
      lackmature CD27low NK cells to study the distinct roles of CD27low versus
      CD27high NK cells in a model of Tcell-mediated skin transplant rejection under
      costimulatory blockade conditions. RESULTS: We found that T cell-reconstituted
      Rag1-/- recipients (possessing CD27low NK cells) show significantly prolonged
      allograft survival on costimulatory blockade when compared to Rag1-/-T-bet-/-
      mice (lacking CD27low NK cells), indicating that CD27low but not CD27high NK
      cells enhance allograft survival. Critically, Rag1-/-T-bet-/- recipients showed
      strikingly increased alloreactive memory CD8+ Tcell responses, as indicated by
      increased CD8+ Tcell proliferation and interferon-gamma production. Therefore, we
      speculated that CD27low NK cells directly regulate alloreactive CD8+ Tcell
      responses under costimulatory blockade conditions. To test this, we adoptively
      transferred CD27low NK cells into Rag1-/-T-bet-/- skin transplant recipients and
      found that the CD27low NK cells restore better allograft survival by inhibiting
      the proliferation of alloreactive interferon-gamma+CD8+ T cells. CONCLUSIONS: In
      summary, mature CD27low NK cells promote allograft survival under costimulatory
      blockade conditions by regulating alloreactive memory CD8+ T-cell responses.

PMID- 25606782
TI  - Quality of life in liver transplant candidates: frailty is a better indicator
      than severity of liver disease.
AB  - BACKGROUND: In an effort to understand the diminished quality of life (QoL)
      exhibited by patients with end-stage liver disease (ESLD), we studied the
      association of frailty and severity of liver disease with quality of life in this
      patient population. METHODS: In a prospective, single-center cohort study
      (N=487), we assessed frailty and QoL in patients with ESLD referred for liver
      transplant. Frailty was measured on a scale from 0 to 5 by grip strength, gait
      speed, exhaustion, shrinkage, and physical activity, with scores of 3 or higher
      characterized as frail. Physical, mental, and combined overall quality of life
      scores ranging from 0 to 100 were assessed using Short Form 36. Pearson
      correlation and multiple linear regression were used to identify variables
      associated with QoL. RESULTS: Quality of life was notably low in the study cohort
      (mean: physical, 42.9+/-24.1; mental, 58.3+/-23.2). In multivariate analysis
      adjusted for demographic and clinical characteristics, frailty was significantly
      negative associated with physical (slope, -22.55, 95% confidence interval, -26.39
      to -18.71; P<0.001) and mental QoL (slope, -17.59, 95% confidence interval, 
      21.47 to -13.71; P<0.001). Model for ESLD (MELD) was not associated with QoL.
      CONCLUSION: In ESLD patient referred for liver transplant, diminished QoL appears
      to be significantly negatively associated with frailty and not with severity of
      liver disease as measured MELD. With further study, if frailty is shown to be a
      remediable condition, targeted programs may help decrease frailty and improve
      quality of life in ESLD patients.

PMID- 25606783
TI  - Pretransplant malignancy as a risk factor for posttransplant malignancy after
      heart transplantation.
AB  - BACKGROUND: Posttransplant malignancy is a major cause of death in orthotopic
      heart transplant recipients. Our study objective is to identify whether
      pretransplant malignancy increases the risk for posttransplant malignancy.
      METHODS: Using the Organ Procurement and Transplantation Network/United Network
      for Organ Sharing database, adult (>=18 years old) recipients of a primary
      orthotopic heart transplant performed between 2000 and 2012 were included. The
      cohort was stratified according to the presence and type of pretransplant
      malignancy. Outcomes were posttransplant overall, skin, solid malignancies, and
      posttransplant lymphoproliferative disorder. Incidence of and time to first
      posttransplant malignancy, accounting for death as a competing event, were
      calculated. Fine and Gray competing risks regression was performed to examine
      risk factors associated with posttransplant malignancy. RESULTS: Of 23,171
      recipients, overall posttransplant malignancy was diagnosed in 2673 recipients
      (11.5%).The median time to overall, skin, solid posttransplant malignancies, and
      posttransplant lymphoproliferative disorder were 3.2 (1.6-5.7), 3.2 (1.7-5.6),
      3.5 (1.7-5.9), and 2.5 years(0.8-5.2), respectively. Pretransplant malignancy
      increased the risk of posttransplant overall (subhazard ratio [SHR], 1.51; 95%
      confidence interval [95% CI], 1.27-1.81), skin (SHR, 1.55, 95% CI, 1.23-1.93),
      and solid organ malignancies (SHR, 1.54; 95% CI, 1.13-2.11). Pretransplant skin
      malignancy increased the risk of posttransplant skin malignancy (SHR, 2.79; 95%
      CI, 1.82-4.28). Pretransplant solid malignancy also increased the risk of
      posttransplant skin malignancy (SHR, 1.55; 95% CI, 1.07-2.25) but not of
      posttransplant solid tumors (SHR, 1.23; 95% CI, 0.69-2.19). Older, male, and
      white were also risk factors for posttransplant malignancy. CONCLUSIONS: A
      history of any pretransplant malignancy was associated with increased risks of
      skin and solid malignancies after transplantation. The specific type of
      posttransplant malignancy risk differed according to the type of pretransplant
      malignancy.

PMID- 25606784
TI  - Minimally invasive kidney transplantation: perioperative considerations and key 6
      month outcomes.
AB  - BACKGROUND: Minimally invasive approaches to kidney transplantation (KT) have
      been described recently. However, information concerning perioperative management
      in these patients is lacking. Accordingly, in the current study, we describe our
      perioperative management strategy in patients undergoing robotic KT with regional
      hypothermia and report its safety and efficacy. Further, we describe key 6-month
      outcomes in these patients. METHODS: Sixty-seven consecutive end-stage renal
      disease patients underwent live-donor robotic KT at a single tertiary care
      institution between January 2013 and June 2014. Outcomes including patient/graft
      survival, graft function, operative parameters, and perioperative complications
      are reported in patients with a minimum of 6-month follow-up (n=54). RESULTS: All
      patients successfully underwent robotic KT with regional hypothermia using a
      modified intraoperative management protocol. None of the cases required
      conversion to open surgery (0%). Mean console, warm ischemia, and rewarming times
      were 130.8 minutes, 2.3 minutes and 42.9 minutes, respectively. Mean graft
      surface temperature was 19.2 degrees C with zero incidence of systemic
      hypothermia. Routine extraperitonealization of the graft insured against graft
      torsion (0%) despite a transperitoneal approach to graft placement. There were no
      instances of graft vascular thromboses/stenoses/leaks (0%). Three patients (5.6%)
      developed clinical head-neck edema but were successfully extubated on table.
      There was no delayed graft function (0%). Mean 6-month serum creatinine was 1.2
      mg/dL. Patient survival was 96.3% (n=52), and death-censored graft survival was
      100% at a median follow-up of 13.4 months. CONCLUSIONS: Significant differences
      exist in intraoperative management of patients undergoing robotic KT and open KT.
      By tweaking fluid infusion rates and pneumatic pressures and maintaining core
      body temperature, optimal patient outcomes can be achieved. Pretransplant and
      posttransplant management is essentially the same.

PMID- 25606785
TI  - A phase I/II placebo-controlled trial of C1-inhibitor for prevention of antibody
      mediated rejection in HLA sensitized patients.
AB  - BACKGROUND: Antibody-mediated rejection (AMR) is a severe form of rejection,
      mediated primarily by antibody-dependent complement (C) activation. C1 inhibitor
      (C1-INH, Berinert) inhibits the classical and lectin pathways of C activation. We
      performed a randomized, placebo-controlled study using C1-INH in highly
      sensitized renal transplant recipients for prevention of AMR. METHODS: Twenty
      highly sensitized patients desensitized with IVIG+rituximab+/-plasma exchange
      were enrolled and randomized 1:1 to receive plasma-derived human C1-INH (20
      IU/kg/dose) versus placebo intraoperatively, then twice weekly for 7 doses. Renal
      function, adverse events (AEs)/serious AEs, C3, C4, and C1-INH levels were
      monitored and C1q+ HLA antibodies were also blindly assessed. RESULTS: One
      patient in the C1-INH group versus 2 patients in the placebo group developed
      serious AEs, but none were related to study drug. Delayed graft function
      developed in 1 C1-INH subject and 4 in the placebo. The C1-INH trough levels
      increased with C1-INH treatment. C3 and C4 levels also increased significantly in
      the C1-INH group compared to placebo. No C1-INH patient developed AMR during the
      study. Two patients developed AMR after the study. Three placebo patients
      developed AMR, one during the study. C1q+ donor specific antibodies were reduced
      in 2 C1-INH treated patients tested, while immunoglobulin G DSA levels showed
      decreased binding for both groups. CONCLUSIONS: The C1-INH appears safe in the
      posttransplant period. The C1-INH treatment may reduce ischemia-reperfusion
      injury. The C1-INH also resulted in significant elevations of C1-INH levels, C3,
      C4, and reduced C1q+ HLA antibodies. Taken together, the combination of antibody
      reduction and C1-INH may prove useful in prevention of AMR. Further controlled
      studies are warranted.

PMID- 25606786
TI  - Three-dimensional structural modelling and calculation of electrostatic
      potentials of HLA Bw4 and Bw6 epitopes to explain the molecular basis for
      alloantibody binding: toward predicting HLA antigenicity and immunogenicity.
AB  - BACKGROUND: We have previously shown that qualitative assessment of surface
      electrostatic potential of HLA class I molecules helps explain serological
      patterns of alloantibody binding. We have now used a novel computational approach
      to quantitate differences in surface electrostatic potential of HLA B-cell
      epitopes and applied this to explain HLA Bw4 and Bw6 antigenicity. METHODS:
      Protein structure models of HLA class I alleles expressing either the Bw4 or Bw6
      epitope (defined by sequence motifs at positions 77 to 83) were generated using
      comparative structure prediction. The electrostatic potential in 3-dimensional
      space encompassing the Bw4/Bw6 epitope was computed by solving the Poisson
      Boltzmann equation and quantitatively compared in a pairwise, all-versus-all
      fashion to produce distance matrices that cluster epitopes with similar
      electrostatics properties. RESULTS: Quantitative comparison of surface
      electrostatic potential at the carboxyl terminal of the alpha1-helix of HLA class
      I alleles, corresponding to amino acid sequence motif 77 to 83, produced
      clustering of HLA molecules in 3 principal groups according to Bw4 or Bw6 epitope
      expression. Remarkably, quantitative differences in electrostatic potential
      reflected known patterns of serological reactivity better than Bw4/Bw6 amino acid
      sequence motifs. Quantitative assessment of epitope electrostatic potential
      allowed the impact of known amino acid substitutions (HLA-B*07:02 R79G, R82L,
      G83R) that are critical for antibody binding to be predicted. CONCLUSIONS: We
      describe a novel approach for quantitating differences in HLA B-cell epitope
      electrostatic potential. Proof of principle is provided that this approach
      enables better assessment of HLA epitope antigenicity than amino acid sequence
      data alone, and it may allow prediction of HLA immunogenicity.

PMID- 25606787
TI  - Discrepancies between beliefs and behavior: a prospective study into
      immunosuppressive medication adherence after kidney transplantation.
AB  - BACKGROUND: Nonadherence to immunosuppressive medication after kidney
      transplantation is a behavioral issue and as such it is important to understand
      the psychological factors that influence this behavior. The aim of this study was
      to investigate the extent to which goal cognitions, illness perceptions, and
      treatment beliefs were related to changes in self-reported immunosuppressive
      medication adherence up to 18 months after transplantation. METHODS: Interviews
      were conducted with patients in the outpatient clinic 6 weeks (T1; n=113), 6
      months (T2; n=106), and 18 months (T3; n=84) after transplantation. Self-reported
      adherence was measured using the Basel Assessment of Adherence to
      Immunosuppressive Medications Scale Interview. Psychological concepts were
      measured using the Brief Illness Perceptions Questionnaire, Beliefs about
      Medicines Questionnaire, and questions on the importance of adherence as a
      personal goal, conflict with other goals, and self-efficacy for goal attainment.
      RESULTS: Nonadherence significantly increased over time to 31% at T3. Perceived
      necessity of medication, perceived impact of transplant on life (consequences)
      and emotional response to transplantation significantly decreased over time.
      Participants who reported low importance of medication adherence as a personal
      goal were more likely to become nonadherent over time. CONCLUSIONS: Illness
      perceptions can be described as functional and supportive of adherence which is
      inconsistent with the pervasive and increasing nonadherence observed. There
      appears therefore to be a discrepancy between beliefs about adherence and actual
      behavior. Promoting (intrinsic) motivation for adherence goals and exploring the
      relative importance in comparison to other personal goals is a potential target
      for interventions.

PMID- 25606788
TI  - Clinical outcomes associated with induction regimens among retransplant kidney
      recipients in the United States.
AB  - BACKGROUND: Numerous studies have evaluated outcomes and risk factors associated
      with induction protocols among kidney transplant recipients. However, few studies
      have evaluated outcomes in the subset of retransplant recipients who often have
      unique immunologic condition and risk profile and represent an increasing
      proportion of transplant patients in the United States. METHODS: We evaluated the
      association of common induction treatments (alemtuzumab, thymoglobulin,
      interleukin-2 receptor blockers, and no induction) given at transplantation with
      clinical outcomes among adult recipients retransplant between 2003 and 2011 using
      national Scientific Registry of Transplant Recipients data (n = 14,336). We used
      a propensity score analysis to minimize potential selection biases for allocation
      of treatment. RESULTS: In adjusted models, there were no significant differences
      between induction groups for outcomes of delayed graft function, 1-year acute
      rejection, 1-year BK virus or patient death. Acute rejection before hospital
      discharge was lowest among patients treated with thymoglobulin and alemtuzumab.
      The no induction group had the highest average 1-year estimated glomerular
      filtration rate (62 mL/min/1.73 kg/m(2)) and lowest incidence of any malignancies
      within 1 year (1.0%). Hospitalizations after transplantation were highest among
      patients treated with thymoglobulin (42% at 1 year). Recipients with alemtuzumab
      had the highest relative risk for graft loss (adjusted hazard ratio, 1.19; 95%
      confidence interval, 1.01-1.40, relative to patients treated with thymoglobulin).
      CONCLUSION: There is moderate variation in clinical outcomes associated with
      induction treatment among retransplant kidney recipients in the United States,
      including higher graft loss rates among recipients treated with alemtuzumab but
      similar patient survival between all regimens.

PMID- 25606789
TI  - VEGF-trap aflibercept significantly improves long-term graft survival in high
      risk corneal transplantation.
AB  - BACKGROUND: Graft failure because of immune rejection remains a significant
      problem in organ transplantation, and lymphatic and blood vessels are important
      components of the afferent and efferent arms of the host alloimmune response,
      respectively. We compare the effect of antihemangiogenic and antilymphangiogenic
      therapies on alloimmunity and graft survival in a murine model of high-risk
      corneal transplantation. METHODS: Orthotopic corneal transplantation was
      performed in hemevascularized and lymph-vascularized high-risk host beds, and
      graft recipients received subconjunctival vascular endothelial growth factor
      (VEGF)-trap, anti-VEGF-C, sVEGFR-3, or no treatment, beginning at the time of
      surgery. Fourteen days after transplantation, graft hemeangiogenesis and
      lymphangiogenesis were evaluated by immunohistochemistry. The frequencies of Th1
      cells in regional lymphoid tissue and graft-infiltrating immune cells were
      evaluated by flow cytometry. Long-term allograft survival was compared using
      Kaplan-Meier curves. RESULTS: VEGF-trap significantly decreased graft
      hemangiogenesis as compared to the control group and was most effective in
      reducing the frequency of graft-infiltrating immune cells. Anti-VEGF-C and
      sVEGFR3 significantly decreased graft lymphangiogenesis and lymphoid Th1 cell
      frequencies as compared to control. VEGF-trap (72%), anti-VEGF-C (25%), and
      sVEGFR-3 (11%) all significantly improved in the 8-week graft survival compared
      to control (0%), although VEGF-trap was significantly more effective than both
      anti-VEGF-C (P < 0.05) and sVEGFR-3 (P < 0.05). CONCLUSION: In a clinically
      relevant model of high-risk corneal transplantation in which blood and lymphatic
      vessels are present and treatment begins at the time of transplantation, VEGF
      trap is significantly more effective in improving long-term graft survival as
      compared to anti-VEGF-C and sVEGFR-3, but all approaches improve survival when
      compared to untreated control.

PMID- 25606790
TI  - Gastrointestinal Endoscopy Is Safe in Patients Before and After Lung or Heart
      Transplantation.
AB  - BACKGROUND: Gastrointestinal complications are common in patients after lung and
      heart transplantation. Endoscopy is a standard method for the assessment of
      gastrointestinal morbidities. The aim of this study was to analyze the number and
      type of complications during endoscopic procedures in patients before and after
      lung or heart transplantation. METHODS: A retrospective single centre analysis of
      endoscopic procedures in patients before and after lung and heart transplantation
      from May 1999 to September 2012 was performed compared to a control group.
      RESULTS: Four hundred fifty-nine endoscopic procedures were performed in 175
      patients after transplantation (84 lung and 91 heart) and 213 procedures in 160
      transplant candidates on the waiting list for lung (n = 126) or heart (n = 34)
      transplantation. In 26% (n = 56/214) of the endoscopic examinations, an
      intervention was necessary in the lung transplant group compared to 32% (n =
      79/245) in the heart transplant group and 27% (n = 43/160) and 21% (n = 11/53) in
      the lung and heart transplant candidates, respectively. In the control group,
      endoscopic interventions were performed in 24% (n = 195/805) of the examinations.
      Overall, 14 (1%) complications resulted from 1,477 endoscopic examinations. Only
      four (0.9%) of 459 endoscopic examinations were followed by complications in the
      transplant recipients, whereas in the control group, 10 complications (1.2%) of
      805 endoscopies were documented. No endoscopic complication occurred in the lung
      and heart transplant candidates. CONCLUSION: Diagnostic and therapeutic
      endoscopies can be safely performed after lung and heart transplantation and in
      patients on the waiting list for these organs.

PMID- 25606791
TI  - Living Donor Liver Transplantation in Patients 70 Years or Older.
AB  - INTRODUCTION: Previous published studies have shown that age is not a
      contraindication for deceased donor liver transplantation. The data about elderly
      recipient after living donor liver transplantation (LDLT) is unsatisfactory. The
      aim of this study was to evaluate the outcome of the LDLT with recipients aged 70
      years or older. PATIENTS AND METHODS: Between 2005 and 2013, 469 patients
      underwent LDLTs. The clinical characteristics, preoperative, intraoperative, and
      postoperative data, graft, and patients' survival of these patients were
      retrospectively analyzed. All recipients who were 70 years or older at the time
      of liver transplantation were indentified. The results were compared to the
      results of the patients younger than 70 years. RESULTS: There were 12 patients
      (2%) 70 years or older. All patients received the right lobe of their donor in a
      standard technique. One patient died postoperatively because of pulmonary
      infection, and one patient died 6 months after the operation because of graft
      failure after cardiac infarction. The comorbidity score of these two patients
      were significantly higher compared to the other ten patients without any
      complications (8.5 vs. 4.6, P = 0.01). The 1-year and 3-year patient and graft
      survival was 84%. There were no significant differences in complications,
      hospital stay, perioperative mortality, or median survival compared to the
      younger group. CONCLUSION: Although the number of the patients is small, our
      study emphasizes that LDLT of patients 70 years or older can be performed safely
      in patients without major comorbidities. Elderly patients with increased risk for
      postoperative complications should be excluded from LDLT.

PMID- 25606792
TI  - Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly
      Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.
AB  - BACKGROUND: Desensitization with intravenous immunoglobulin and rituximab (I+R)
      significantly improves transplant rates in highly sensitized patients, but
      antibody-mediated rejection (ABMR) remains a concern. PATIENTS AND METHODS:
      Between July 2006 and December 2012, 226 highly sensitized patients received
      transplants after desensitization. Most received alemtuzumab induction and
      standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n
      = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed.
      RESULTS: Significant risks for ABMR included previous transplants and pregnancies
      as sensitizing events, donor-specific antibody (DSA) relative intensity scores
      greater than 17, presence of both class I and II DSAs at transplant and time on
      waitlist. The ABMR showed a significant benefit for graft survival and glomerular
      filtration rate at 5 years (P < 0.0001). Banff pathology characteristics for ABMR
      patients with or without graft loss did not differ. C4d versus C4d ABMR did not
      predict graft loss (P = 0.086). Thrombotic microangiopathy (TMA) significantly
      predicted graft failure (P = 0.045). The ABMR episodes were treated with I+R (n =
      25), or, in more severe ABMR, plasma exchange (PLEX)+I+R (n = 20). Graft survival
      for patients treated with I+R was superior (P = 0.028). Increased mortality was
      seen in ABMR patients experiencing graft loss after ABMR treatment (P = 0.004).
      The PLEX + Eculizumab improved graft survival for TMA patients (P = 0.036).
      CONCLUSION: Patients desensitized with I+R who remain ABMR have long-term graft
      and patient survival. The ABMR patients have significantly reduced graft survival
      and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes
      benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores
      at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance
      and reduction strategies before transplantation are critical to avoiding ABMR and
      improving long-term outcomes.

PMID- 25606793
TI  - Noninvasive diagnosis of dysfunctions in patients after organ transplantation by
      monitoring the redox potential of blood serum.
AB  - BACKGROUND: The problem of noninvasive diagnosis of transplant dysfunction in
      patients is one of the most complex problems in transplantology at the present
      time. Because transplanted organs can be ischemic, the measurement of redox
      potential (RP) in blood serum reflects the prooxidant-antioxidant balance in the
      organism. It was hypothesized that certain dysfunctions and postoperative
      complications in transplant patients may be accompanied by a change in the RP of
      blood plasma. METHODS: Monitoring of the RP in the blood serum of patients was
      performed as a noninvasive method of diagnosis of transplant dysfunctions. The RP
      values were measured in blood serum of 63 apparently healthy subjects. Monitoring
      of blood serum RP was performed in 64 liver transplant patients, 59 kidney
      allotransplantation patients and six lung transplant patients. A total of 1,759
      measurements were performed in 192 total subjects. Statistical analysis of RP
      values was performed using the Statistica 6.0 software package. RESULTS AND
      CONCLUSION: The proposed method is based on the electrochemical measurement of
      the open-circuit potential of the platinum electrode immersed in blood serum
      because the measured value reflects the state of equilibrium between prooxidant
      and antioxidant systems of the organism. Shifts in values of the RPs (open
      circuit potentials) observed in the course of monitoring are significantly
      different in patients with transplant dysfunction compared to patients with
      unremarkable recoveries. The analysis of monitoring allows for the development of
      certain diagnostic and prognostic criteria of transplant dysfunction. It is
      important that the proposed method is noninvasive, simple, and inexpensive.

PMID- 25606794
TI  - Understanding Patient Barriers to Kidney Transplant Evaluation.
AB  - BACKGROUND: Some patients referred for kidney transplant evaluation fail to
      attend the visit. Our goal was to compare demographic, socioeconomic, and
      psychologic factors between evaluation visit attendees and absentees. METHODS: A
      convenience sample of patients referred and scheduled for kidney transplant
      evaluation at a single center from November 2012 to December 2013 participated in
      a phone survey reporting socioeconomic, demographic, and clinical
      characteristics; health literacy; and perceived knowledge and concerns about
      transplantation. Absentees were matched by race with attendees. Analyses of
      differences between groups were performed with chi-square test, Fisher exact
      test, and t tests. Multivariable logistic regression was adjusted for relevant
      demographic characteristics. RESULTS: One hundred four adults participated (61%
      men, 46% white, 52 +/- 12 years). Financial concerns were the most prevalent
      (67.3% affording medication, 64.1% affording operation). Previous evaluation at a
      different transplant center (P = 0.029) and being on dialysis (P = 0.008) were
      significantly associated with absence. Attendance was associated with concerns
      about finding a living donor (P = 0.038) and higher perceived general knowledge
      about transplantation (P <= 0.001). No differences were appreciated in
      demographic, socioeconomic, or health literacy factors between groups.
      CONCLUSION: Both attendee and absentee patients were most concerned with the
      financial burden of kidney transplantation. Although concerns and perceived
      knowledge are important correlates of behavior, other considerations such as
      psychologic factors and prior medical experiences may influence patients' ability
      to complete the kidney transplant evaluation process. Although this pilot study
      was conducted in a small sample and has limited generalizability, our findings
      can guide future research.

PMID- 25606795
TI  - Use of Heavy Drinking Donors in Heart Transplantation is Not Associated With
      Worse Mortality.
AB  - BACKGROUND: Although orthotopic heart transplantation (OHT) remains the preferred
      treatment for end-stage heart failure, there continues to be a critical shortage
      of organ donors. The goal of this study is to examine outcomes after orthotopic
      OHT using heavy drinking donors (HDDs) in a large, national database. METHODS:
      The United Network for Organ Sharing database was examined for all primary, adult
      OHT carried out from 2005 to 2012. RESULTS: There were 14,928 total OHT performed
      during the study period with 2,274 (15.2%) using HDD. Recipients of HDD were
      older (53.4 vs. 51.9 years, P < 0.001), more likely men (80.7 vs 74.4%, P <
      0.001), less likely sex mismatched (21.5 vs 27.5%, P < 0.001), more likely race
      mismatched (57.4 vs 52.4%, P < 0.001), and had less total HLA mismatches (4.55 vs
      4.65, P < 0.001). The HDD were older (37.0 vs 30.5 years, P < 0.001), more likely
      men (82.2 vs 69.9%, P < 0.001), and more likely to have heavy cigarette use (38.1
      vs 13.2%, P < 0.001). Length of stay was not different (20.3 vs 19.7 days, P =
      0.02). On multivariate analysis, use of HDD was not associated with mortality at
      30 days (hazards ratio [HR], 1.12; 95% confidence interval [95% CI], 0.90-1.39; P
      = 0.30), 1 year (HR, 0.96; 95% CI, 0.83-1.11; P = 0.56), and at 5 years (HR,
      1.02; 95% CI, 0.91-1.13; P = 0.79). Variables associated with mortality at 5
      years included increasing donor age, prolonged ischemic time, worsening recipient
      creatinine, recipient black race, sex mismatch, and extracorporeal membrane
      oxygenation or mechanical ventilation as a bridge to transplantation. CONCLUSION:
      Heart transplantation can be performed using carefully selected HDDs with good
      outcomes.

PMID- 25606796
TI  - The Effect of Mammalian Target of Rapamycin Versus Calcineurin Inhibitor-based
      Immunosuppression on Measured Versus Estimated Glomerular Filtration Rate After
      Orthotopic Liver Transplantation.
AB  - INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors have been proposed
      to preserve renal function in patients after orthotopic liver transplantation
      (OLT) based on estimated glomerular filtration rate (eGFR). The presented study
      evaluated their effect on renal function in comparison to calcineurin inhibitors
      (CNIs) defined by measured GFR. METHODS: Renal function was measured in patients
      on mTOR-based (n=28) or on CNI-based (n=51) immunosuppression after OLT by
      performing inulin clearance (IC) as well as eGFR based on the Modification of
      Diet in Renal Disease (MDRD4) Study and the chronic kidney disease epidermiology
      (CKD-EPI) formula at baseline, 6, 12, 18, and 24 months. Statistical analysis was
      performed by using analysis of variance and serial measurement testing. RESULTS:
      The MDRD4 and the IC values differed significantly at study inclusion in both
      groups (mTOR and CNI group, P=0.001), whereas the CKD-EPI and the IC values did
      not. Estimated GFR by the MDRD4 results declined throughout the study period in
      patients on CNI and in patients on mTOR (CNI, 81 vs. 61 mL/min/1.73 m(2), P=0.01;
      82 vs. 60 mL/min/1.73 m(2), P=0.01), whereas CKD EPI and measured GFR did not
      change throughout the study period in the CNI. CONCLUSION: The use of eGFR
      especially the MDRD-based formula, in OLT patients, leads to incorrect
      interpretation of their renal function.

PMID- 25606797
TI  - Reduced rate of cardiovascular death after cytomegalovirus prophylaxis in renal
      transplant recipients.
AB  - BACKGROUND: It is unknown how death with a functioning graft (DWFG) is affected
      in renal transplant recipients who receive prophylaxis for cytomegalovirus (CMV)
      infection. METHODS: Data from 61,927 adult recipients of a deceased donor kidney
      transplant in 1990 to 2012 registered with the Collaborative Transplant Study
      were analyzed. RESULTS: Cytomegalovirus prophylaxis was administered in 18%, 75%,
      27% and 34% of R-/D- (recipient-negative, donor-negative), R-/D+, R+/D- and R+/D+
      transplants, respectively. Only in R-/D+ transplants was CMV prophylaxis
      associated with significantly improved patient survival versus no prophylaxis
      (P<0.001). Unexpectedly, in the R-/D+ subgroup, DWFG because of infection was not
      significantly affected by use of CMV prophylaxis (P=0.16) but death from
      cardiovascular disease was significantly lower (P<0.001). Cox regression analysis
      confirmed that the primary impact of CMV prophylaxis on DWFG in R-/D+ transplants
      was because of reduced cardiovascular death (hazard ratio, 0.66; 95% confidence
      interval, 0.51-0.85; P=0.002), an effect restricted to patients aged 40 years or
      older (hazard ratio, 0.61; 95% confidence interval, 0.46-0.81; P<0.001).
      CONCLUSION: We conclude that CMV prophylaxis is associated with a significant
      benefit for risk of cardiovascular DWFG among R-/D+ kidney transplant patients
      aged >= 40 years. Cytomegalovirus prophylaxis appears particularly critical in
      this patient subpopulation.

PMID- 25606798
TI  - Normothermic preservation of the rat hind limb with artificial oxygen-carrying
      hemoglobin vesicles.
AB  - BACKGROUND: For managing major limb amputation, it is important to consider
      ischemic time and reperfusion injury by free radicals after the blood supply is
      reestablished. State of preservation during transplant surgery is crucial for the
      survival and function of the tissue, graft, or organ. In this study, we confirmed
      the effect of intermittent blood flow in rat ischemic hind limb and developed a
      new oxygenic preservation method using artificial oxygen carrying hemoglobin
      vesicles (HbVs). METHODS: We first compared a continuous ischemic model and an
      intermittent reflow model on rat hind limb. At postoperative day 7, hind limbs
      were evaluated. Next, we performed total amputation, normothermic preservation by
      perfusion with extracellular-trehalose-Kyoto (ETK) solution or HbV, and
      microsurgical replantation of the left hind limb. Venous efflux was analyzed, the
      amputated limb evaluated after 6 hr perfusion, and the replantation outcome of
      each model was compared. RESULTS: In our early study, 24 hr continuous ischemic
      model necrotized, but intermittent reflow model almost survived except for
      partial necrosis at postoperative day 7. Scar tissue on the right limb showed
      myonecrosis and infiltration of inflammatory cells. Skeletal muscle on the right
      limb was structurally well maintained. Hemoglobin vesicle-treated limbs appeared
      to have much better oxygenation than ETK-treated limbs. Aerobic respiration
      remained in the amputated limb, gastrocnemius muscle was well maintained, and the
      overall replantation was successful in the limb preserved using HbV. CONCLUSION:
      These studies demonstrated that oxygenic preservation is effective for rat
      ischemic limb, suggesting that this method may be useful for other replantation
      and transplantation surgeries.

PMID- 25606799
TI  - Identifying Opportunities to Increase the Throughput of Kidney Paired Donation.
AB  - BACKGROUND: Although kidney paired donation (KPD) has led to thousands of
      transplants, the 2012 KPD Consensus Conference concluded that more could be done.
      Perceptions are that a large number of match offers never resulted in
      transplantations, and unfruitful matches have both financial and emotional costs.
      METHODS: To describe, quantify, and analyze the unrealized match offers, we
      studied the matching process from registration to transplantation in the National
      Kidney Registry, a large KPD registry, over a 25-month period. RESULTS: Of the
      3,180 match offers, 454 were turned down. The most common reasons were the donor
      was not acceptable (50%) and their recipient had unacceptably high donor-specific
      antibodies (28%). Of the 2,228 accepted offers, 1,335 advanced to the cell-based
      cross-match stage because 893 of these were part of chains that fell through.
      Fifty-five of 887 recorded cell-based cross-matches were positive, 20 donors were
      unacceptable, and 22 recipients had unacceptably high donor-specific antibodies.
      Six hundred ninety transplantations were performed. CONCLUSION: Despite the
      success of KPD, by analyzing the matching process, we identify several strategies
      to increase the number of KPD transplantations, including recruiting more
      participants, processing the match offers more quickly at the transplant center
      level, enhancing the donor preselection tools, improving communication between
      centers and the registries, and combining desensitization with KPD.

PMID- 25606802
TI  - Synthesis of large single-crystal hexagonal boron nitride grains on Cu-Ni alloy.
AB  - Hexagonal boron nitride (h-BN) has attracted significant attention because of its
      superior properties as well as its potential as an ideal dielectric layer for
      graphene-based devices. The h-BN films obtained via chemical vapour deposition in
      earlier reports are always polycrystalline with small grains because of high
      nucleation density on substrates. Here we report the successful synthesis of
      large single-crystal h-BN grains on rational designed Cu-Ni alloy foils. It is
      found that the nucleation density can be greatly reduced to 60 per mm(2) by
      optimizing Ni ratio in substrates. The strategy enables the growth of single
      crystal h-BN grains up to 7,500 MUm(2), approximately two orders larger than that
      in previous reports. This work not only provides valuable information for
      understanding h-BN nucleation and growth mechanisms, but also gives an effective
      alternative to exfoliated h-BN as a high-quality dielectric layer for large-scale
      nanoelectronic applications. 

PMID- 25606807
TI  - Too Much of a Good Thing? Emotional Intelligence and Interpersonal Conflict
      Behaviors.
AB  - Research suggests that the outcomes of interpersonal conflict are determined not
      only by the conflict itself, but also by the way in which it is handled.
      Confrontational and domineering tactics have been found to magnify the adverse
      impact of conflict. Thus, investigations of determinants of aggressive conflict
      management behaviors are of considerable interest. This study extends the
      literature by examining the relationship between conflict management preferences
      and conflict management behaviors and by examining how emotional intelligence
      (EI) shapes this preference-behavior relationship. Individuals' conflict
      management preferences predicted actual conflict management behaviors. EI was
      found to moderate this relationship. However, some of these moderating effects
      run contrary to the popular view of EI as a prosocial concept. Specifically, some
      EI facets were found to strengthen the link between aggressive conflict
      management preferences and subsequent conflict management behaviors. 

PMID- 25606808
TI  - Polymorphic blistering eruption and stomatitis in a patient with non-Hodgkin
      lymphoma.

PMID- 25606800
TI  - Vascular endothelial growth factor c/vascular endothelial growth factor receptor
      3 signaling regulates chemokine gradients and lymphocyte migration from tissues
      to lymphatics.
AB  - BACKGROUND: Circulation of leukocytes via blood, tissue and lymph is integral to
      adaptive immunity. Afferent lymphatics form CCL21 gradients to guide dendritic
      cells and T cells to lymphatics and then to draining lymph nodes (dLN). Vascular
      endothelial growth factor C and vascular endothelial growth factor receptor 3
      (VEGFR-3) are the major lymphatic growth factor and receptor. We hypothesized
      these molecules also regulate chemokine gradients and lymphatic migration.
      METHODS: CD4 T cells were injected into the foot pad or ear pinnae, and migration
      to afferent lymphatics and dLN quantified by flow cytometry or whole mount
      immunohistochemistry. Vascular endothelial growth factor receptor 3 or its
      signaling or downstream actions were modified with blocking monoclonal antibodies
      (mAbs) or other reagents. RESULTS: Anti-VEGFR-3 prevented migration of CD4 T
      cells into lymphatic lumen and significantly decreased the number that migrated
      to dLN. Anti-VEGFR-3 abolished CCL21 gradients around lymphatics, although CCL21
      production was not inhibited. Heparan sulfate (HS), critical to establish CCL21
      gradients, was down-regulated around lymphatics by anti-VEGFR-3 and this was
      dependent on heparanase-mediated degradation. Moreover, a Phosphoinositide 3
      kinase (PI3K)alpha inhibitor disrupted HS and CCL21 gradients, whereas a PI3K
      activator prevented the effects of anti-VEGFR-3. During contact hypersensitivity,
      VEGFR-3, CCL21, and HS expression were all attenuated, and anti-heparanase or
      PI3K activator reversed these effects. CONCLUSIONS: Vascular endothelial growth
      factor C/VEGFR-3 signaling through PI3Kalpha regulates the activity of
      heparanase, which modifies HS and CCL21 gradients around lymphatics. The
      functional and physical linkages of these molecules regulate lymphatic migration
      from tissues to dLN. These represent new therapeutic targets to influence
      immunity and inflammation.

PMID- 25606801
TI  - MicroRNA-10b is upregulated and has an invasive role in colorectal cancer through
      enhanced Rhoc expression.
AB  - We found that the difference in miR-10b expression between the tumor tissue and
      adjacent non-tumor tissue was significant. Outer periphery and portal vein serum
      miR-10b concentrations were significantly higher than those of the control.
      However, the outer periphery vein miR-10b concentrations were not significant
      when compared with the portal vein serum concentration in colorectal cancer. The
      expression levels of miR-10b were associated with higher-grade colorectal cancer.
      MiR-10b levels were markedly elevated in lymph node metastasis-positive tumor
      tissue compared with those in lymph node metastasis-free tumor tissue, and were
      correlated with a downregulation in Hoxd10 expression. Rhoc protein expression in
      tumor tissue was significantly amplified when compared to that of the control
      tissue group. An inverse correlation between Hoxd10 and Rhoc in
      immunohistochemistry and western blot analysis was observed (P<0.05). MiR-10b
      expression was also inversely correlated with Hoxd10 protein expression (P<0.05).
      Thus, miR-10b is potentially involved in the invasion of colorectal cancer.

PMID- 25606809
TI  - Statistical methods of risk-adjusted statistical process control charts to assess
      surgical performance in consecutive colorectal operations at a single
      institution.

PMID- 25606810
TI  - A versatile valving toolkit for automating fluidic operations in paper
      microfluidic devices.
AB  - Failure to utilize valving and automation techniques has restricted the
      complexity of fluidic operations that can be performed in paper microfluidic
      devices. We developed a toolkit of paper microfluidic valves and methods for
      automatic valve actuation using movable paper strips and fluid-triggered
      expanding elements. To the best of our knowledge, this is the first functional
      demonstration of this valving strategy in paper microfluidics. After introduction
      of fluids on devices, valves can actuate automatically after a) a certain period
      of time, or b) the passage of a certain volume of fluid. Timing of valve
      actuation can be tuned with greater than 8.5% accuracy by changing lengths of
      timing wicks, and we present timed on-valves, off-valves, and diversion (channel
      switching) valves. The actuators require ~30 MUl fluid to actuate and the time
      required to switch from one state to another ranges from ~5 s for short to ~50 s
      for longer wicks. For volume-metered actuation, the size of a metering pad can be
      adjusted to tune actuation volume, and we present two methods - both methods can
      achieve greater than 9% accuracy. Finally, we demonstrate the use of these valves
      in a device that conducts a multi-step assay for the detection of the malaria
      protein PfHRP2. Although slightly more complex than devices that do not have
      moving parts, this valving and automation toolkit considerably expands the
      capabilities of paper microfluidic devices. Components of this toolkit can be
      used to conduct arbitrarily complex, multi-step fluidic operations on paper-based
      devices, as demonstrated in the malaria assay device. 

PMID- 25606811
TI  - Evaluating enhanced sulfate reduction and optimized volatile fatty acids (VFA)
      composition in anaerobic reactor by Fe (III) addition.
AB  - Anaerobic reactors with ferric iron addition have been experimentally
      demonstrated to be able to simultaneously improve sulfate reduction and organic
      matter degradation during sulfate-containing wastewater treatment. In this work,
      a mathematical model is developed to evaluate the impact of ferric iron addition
      on sulfate reduction and organic carbon removal as well as the volatile fatty
      acids (VFA) composition in anaerobic reactor. The model is successfully
      calibrated and validated using independent long-term experimental data sets from
      the anaerobic reactor with Fe (III) addition under different operational
      conditions. The model satisfactorily describes the sulfate reduction, organic
      carbon removal and VFA production. Results show Fe (III) addition induces the
      microbial reduction of Fe (III) by iron reducing bacteria (IRB), which
      significantly enhances sulfate reduction by sulfate reducing bacteria (SRB) and
      subsequently changes the VFA composition to acetate-dominating effluent.
      Simultaneously, the produced Fe (II) from IRB can alleviate the inhibition of
      undissociated H2S on microorganisms through iron sulfide precipitation, resulting
      in further improvement of the performance. In addition, the enhancement on
      reactor performance by Fe (III) is found to be more significantly favored at
      relatively low organic carbon/SO4(2-) ratio (e.g., 1.0) than at high organic
      carbon/SO4(2-) ratio (e.g., 4.5). The Fe (III)-based process of this work can be
      easily integrated with a commonly used strategy for phosphorus recovery, with the
      produced sulfide being recovered and then deposited into conventional chemical
      phosphorus removal sludge (FePO4) to achieve FeS precipitation for phosphorus
      recovery while the required Fe (III) being acquired from the waste ferric sludge
      of drinking water treatment process, to enable maximum resource recovery/reuse
      while achieving high-rate sulfate removal. 

PMID- 25606812
TI  - Fucoidan protects ARPE-19 cells from oxidative stress via normalization of
      reactive oxygen species generation through the Ca2+-dependent ERK signaling
      pathway.
AB  - Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and
      it is the main cause of loss of vision. In previous years, interest in the
      biological activities of marine organisms has intensified. The effect of fucoidan
      from the seaweed Fucus vesiculosus on the molecular mechanisms of numerous
      diseases has been studied, while to date, its effect on DR was yet to be
      investigated. Therefore, the aim of the present study was to evaluate the role of
      fucoidan in DR. The human retinal pigment epithelial cell line ARPE-19 was
      exposed to high D-glucose in the presence or absence of fucoidan. Cell viability
      was monitored using MTT and lactate dehydrogenase assays. The intracellular
      reactive oxygen species (ROS) generation was measured using fluorescence
      spectrophotometry. Cell apoptosis was measured by flow cytometry using Annexin V
      fluorescein isothiocyanate staining. Ca2+ influx was measured with a calcium
      imaging system and the activation of the extracellular signal-regulated kinase
      (ERK) protein was evaluated using western blot analysis. The non-toxic fucoidan
      protected ARPE-19 cells from high glucose-induced cell death and normalized high
      glucose-induced generation of ROS. Fucoidan also inhibited high glucose-induced
      cell apoptosis, as well as the Ca2+ influx and ERK1/2 phosphorylation in ARPE-19
      cells. Taken together, these findings indicated that fucoidan protects ARPE-19
      cells against high glucose-induced oxidative damage via normalization of ROS
      generation through the Ca2+-dependent ERK signaling pathway.

PMID- 25606814
TI  - Femur Rotation Increases Patella Cartilage Stress in Females with Patellofemoral
      Pain.
AB  - PURPOSE: This study aimed to test the hypothesis that internal rotation of the
      femur increases patellofemoral joint stress in persons with patellofemoral pain
      (PFP). METHODS: Patella cartilage stress profiles of nine female participants
      with PFP were obtained during squatting using subject-specific finite element
      (FE) models of the patellofemoral joint (15 degrees  and 45 degrees  of knee
      flexion). Input parameters for the FE model included joint geometry, quadriceps
      muscle forces during squatting, and weight-bearing patellofemoral joint
      kinematics. The femur of each model was then internally rotated 5 degrees  and 10
      degrees  along its long axis beyond that of the natural degree of rotation. Using
      a nonlinear FE solver, quasistatic loading simulations were performed to quantify
      patellofemoral joint stress. RESULTS: Compared with those at the natural position
      of the femur, mean hydrostatic pressure and mean octahedral shear stress were
      significantly higher when the femur was internally rotated 5 degrees  and 10
      degrees . No significant differences in stress variables were observed when the
      femur was rotated from 5 degrees  to 10 degrees . These findings were consistent
      across both knee flexion angles (15 degrees  and 45 degrees ). CONCLUSIONS: The
      finding of elevated hydrostatic pressure and octahedral shear stress with
      internal rotation of the femur supports the premise that females with PFP who
      exhibit abnormal hip kinematics may be exposed to elevated patellofemoral joint
      stress.

PMID- 25606813
TI  - The recombinant maize ribosome-inactivating protein transiently reduces viral
      load in SHIV89.6 infected Chinese Rhesus Macaques.
AB  - Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating
      the large ribosomal RNA and some are found to possess anti-human immunodeficiency
      virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal
      inactivation loop which is proteolytically removed for full catalytic activity.
      Here, we showed that the recombinant active maize RIP protected chimeric simian
      human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood
      mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in
      SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and
      other obvious side-effects was found in the treated macaques. Our work
      demonstrates the potential development of maize RIP as an anti-HIV agent without
      impeding systemic immune functions. 

PMID- 25606815
TI  - Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.
AB  - INTRODUCTION: Adaptive responses to exercise training (ET) are crucial in
      maintaining physiologic homeostasis and health span. Exercise-induced aerobic
      bioenergetic reactions in the mitochondria and cytosol increase production of
      reactive oxygen species, where excess of reactive oxygen species can be scavenged
      by enzymatic and nonenzymatic antioxidants (AO) to protect against deleterious
      oxidative stress. Free radicals, however, have recently been recognized as
      crucial signaling agents that promote adaptive mechanisms to ET, such as
      mitochondrial biogenesis, AO enzyme activity defense system upregulation, insulin
      sensitivity, and glucose uptake in the skeletal muscle. Commonly used
      nonenzymatic AO supplements, such as vitamins C and E, alpha-lipoic acid, and
      polyphenols, in combination with ET, have been proposed as ways to prevent
      exercise-induced oxidative stress and hence improve adaptation responses to
      endurance training. METHODS: During the PubMed search, we selected studies that
      examined and compared ET effects with and without administration of commonly used
      AO supplements. RESULTS: Preclinical and clinical studies to date have shown
      inconsistent results indicating either positive or negative effects of endurance
      training combined with different blends of AO supplements (mostly vitamins C and
      E and alpha-lipoic acid) on redox status, mitochondrial biogenesis pathways, and
      insulin sensitivity. Preclinical reports on ET combined with resveratrol,
      however, have shown consistent positive effects on exercise performance,
      mitochondrial biogenesis, and insulin sensitivity, with clinical trials reporting
      mixed effects. Relevant clinical studies have been few and have used inconsistent
      results and methodology (types of compounds, combinations, and supplementation
      time). CONCLUSIONS: The future studies should investigate the effects of specific
      AO and other popular supplements, such as alpha-lipoic acid and resveratrol, on
      training effects in humans. Of particular importance are older adults who may be
      at higher risk of age-related increased oxidative stress, an impaired AO enzyme
      defense system, and comorbidities such as hypertension, insulin resistance, and
      diabetes.

PMID- 25606816
TI  - Exercise Training and Energy Expenditure following Weight Loss.
AB  - PURPOSE: This study aims to determine the effects of aerobic or resistance
      training on activity-related energy expenditure (AEE; kcal.d(-1)) and physical
      activity index (activity-related time equivalent (ARTE)) following weight loss.
      It was hypothesized that weight loss without exercise training would be
      accompanied by decreases in AEE, ARTE, and nontraining physical activity energy
      expenditure (nonexercise activity thermogenesis (NEAT)) and that exercise
      training would prevent decreases in free-living energy expenditure. METHODS: One
      hundred forty premenopausal women had an average weight loss of 25 lb during a
      diet (800 kcal.d(-1)) of furnished food. One group aerobically trained 3 times
      per week (40 min.d(-1)), another group resistance-trained 3 times per week (10
      exercises/2 sets * 10 repetitions), and the third group did not exercise. Dual
      energy x-ray absorptiometry was used to measure body composition, indirect
      calorimetry was used to measure resting energy expenditure (REE) and walking
      energy expenditure, and doubly labeled water was used to measure total energy
      expenditure (TEE). AEE, ARTE, and nontraining physical activity energy
      expenditure (NEAT) were calculated. RESULTS: TEE, REE, and NEAT all decreased
      following weight loss for the no-exercise group, but not for aerobic and
      resistance trainers. Only REE decreased in the two exercise groups. Resistance
      trainers increased ARTE. HR and oxygen uptake while walking on the flat and up a
      grade were consistently related to TEE, AEE, NEAT, and ARTE. CONCLUSIONS:
      Exercise training prevents a decrease in energy expenditure, including free
      living energy expenditure separate from exercise training, following weight loss.
      Resistance training increases physical activity, whereas economy/ease of walking
      is associated with increased TEE, AEE, NEAT, and ARTE.

PMID- 25606818
TI  - Encapsulation of a Ni salen complex in zeolite Y: an experimental and DFT study.
AB  - It is observed that for a square planar Ni(II)-Schiff base complex of the general
      formula {Ni(II)L}, where L is {L: N,N'-bis(5-hydroxy
      salicylidene)ethylenediamine}, when encapsulated in a supercage of zeolite Y the
      bulky guest complex adopts a non-planar geometry without disturbing the integrity
      of the zeolite framework. Detailed comparative characterization is carried out to
      understand the structural change of the guest complex as a result of steric and
      electronic interactions with the host framework. UV-Vis spectroscopic studies of
      the encapsulated and 'neat' complex show a significant blue shift in the d-d
      transition after encapsulation and the diamagnetic 'neat' complex exhibits
      paramagnetism after encapsulation. DFT studies of the Ni(II)-Schiff base complex
      have been carried out for different spin states in neat and encapsulated form and
      the UV-Vis spectra are simulated using TD-DFT to understand the observed spectra
      in detail.

PMID- 25606817
TI  - Exercise Intensity Thresholds: Identifying the Boundaries of Sustainable
      Performance.
AB  - Critical power (CP), respiratory compensation point (RCP), maximal lactate steady
      state (MLSS), and deoxyhemoglobin breakpoint ([HHb]BP) are alternative functional
      indices that are thought to demarcate the highest exercise intensity that can be
      tolerated for long durations. PURPOSE: We tested the hypothesis that CP, RCP,
      MLSS, and [HHb]BP occur at the same metabolic intensity by examining the
      pulmonary oxygen uptake (V)O2p and power output (PO) associated with each
      "threshold." METHODS: Twelve healthy men (mean +/- SD age, 27 +/- 3 yr) performed
      the following tests on a cycle ergometer: i) four to five exhaustive tests for
      determination of CP, ii) two to three 30-min constant-power trials for MLSS
      determination, and iii) a ramp incremental exercise test from which the VO2p and
      PO at RCP and [HHb]BP were determined. During each trial, breath-by-breath VO2p
      and ventilatory variables were measured with a metabolic cart and flowmeter
      turbine; near-infrared spectroscopy-derived [HHb] was monitored using a frequency
      domain multidistance system, and arterialized capillary blood lactate was sampled
      at regular intervals. RESULTS: There were no differences (P > 0.05) among the
      VO2p values associated with CP, RCP, MLSS, and [HHb]BP (CP, 3.29 +/- 0.48; RCP,
      3.34 +/- 0.45; MLSS, 3.27 +/- 0.44; [HHb]BP, 3.41 +/- 0.46 L.min(-1)); however,
      the PO associated with RCP (262 +/- 48 W) and [HHb]BP (273 +/- 41 W) were greater
      (P < 0.05) than both CP (226 +/- 45 W) and MLSS (223 +/- 39 W), which,
      themselves, were not different (P > 0.05). CONCLUSIONS: Although the standard
      methods for determination of CP, RCP, MLSS, and [HHb]BP are different, these
      indices occur at the same VO2p, suggesting that i) they may manifest as a result
      of similar physiological phenomenon and ii) each provides a valid delineation
      between tolerable and intolerable constant-power exercise.

PMID- 25606820
TI  - SF6(-) photodetachment near the adiabatic limit.
AB  - High sensitivity photodetachment cross-section measurements of SF6(-) are
      performed near the adiabatic threshold limit. The extraction of adiabatic
      detachment energy (ADE) from the high sensitivity measurement of the cross
      section change as a function of photon energy is discussed. Below the vertical
      detachment energy a steep 4 orders of magnitude cross-section drop is observed,
      with cross sections as low as 2 * 10(-6) A(2) measured for photon energies below
      2 eV. The cross-section is fitted with both the expected spectral shape based on
      recently calculated Frank-Condon overlaps and a phenomenological threshold
      function. The resulting 1.7 +/- 0.02 eV ADE values are significantly higher than
      previously recommended experimental ADE values obtained based on kinetics
      modeling, and possible differences between the experimental approaches are
      discussed. 

PMID- 25606819
TI  - Proapoptotic effect of endocannabinoids in prostate cancer cells.
AB  - In the early stages, prostate cancer is androgen- dependent; therefore, medical
      castration has shown significant results during the initial stages of this
      pathology. Despite this early effect, advanced prostate cancer is resilient to
      such treatment. Recent evidence shows that derivatives of Cannabis sativa and its
      analogs may exert a protective effect against different types of oncologic
      pathologies. The purpose of the present study was to detect the presence of
      cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and
      to evaluate the effect of the in vitro use of synthetic analogs. In order to do
      this, we used a commercial cell line and primary cultures derived from prostate
      cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2
      receptors was determined by immunohistochemistry where we showed a higher
      expression of these receptors in later stages of the disease (samples with a high
      Gleason score). Later, treatments were conducted using anandamide, 2-arachidonoyl
      glycerol and a synthetic analog of anandamide, methanandamide. Using the MTT
      assay, we proved that the treatments produced a cell growth inhibitory effect on
      all the different prostate cancer cultures. This effect was demonstrated to be
      dose-dependent. The use of a specific CB1 receptor blocker (SR141716) confirmed
      that this effect was produced primarily from the activation of the CB1 receptor.
      In order to understand the MTT assay results, we determined cell cycle
      distribution by flow cytometry, which showed no variation at the different cell
      cycle stages in all the cultures after treatment. Treatment with endocannabinoids
      resulted in an increase in the percentage of apoptotic cells as determined by
      Annexin V assays and caused an increase in the levels of activated caspase-3 and
      a reduction in the levels of Bcl-2 confirming that the reduction in cell
      viability noted in the MTT assay was caused by the activation of the apoptotic
      pathway. Finally, we observed that endocannabinoid treatment activated the Erk
      pathway and at the same time, produced a decrease in the activation levels of the
      Akt pathway. Based on these results, we suggest that endocannabinoids may be a
      beneficial option for the treatment of prostate cancer that has become
      nonresponsive to common therapies. 

PMID- 25606821
TI  - Functional and Electrical Integration of Induced Pluripotent Stem Cell-Derived
      Cardiomyocytes in a Myocardial Infarction Rat Heart.
AB  - In vitro expanded beating cardiac myocytes derived from induced pluripotent stem
      cells (iPSC-CMs) are a promising source of therapy for cardiac regeneration.
      Meanwhile, the cell sheet method has been shown to potentially maximize survival,
      functionality, and integration of the transplanted cells into the heart. It is
      thus hypothesized that transplanted iPSC-CMs in a cell sheet manner may
      contribute to functional recovery via direct mechanical effects on the myocardial
      infarction (MI) heart. F344/NJcl-rnu/rnu rats were left coronary artery ligated
      (n = 30), followed by transplantation of Dsred-labeled iPSC-CM cell sheets of
      murine origin over the infarct heart surface. Effects of the treatment were
      assessed, including in vivo molecular/cellular evaluations using a synchrotron
      radiation scattering technique. Ejection fraction and activation recovery
      interval were significantly greater from day 3 onward after iPSC-CM
      transplantation compared to those after sham operation. A number of transplanted
      iPSC-CMs were present on the heart surface expressing cardiac myosin or connexin
      43 over 2 weeks, assessed by immunoconfocal microscopy, while mitochondria in the
      transplanted iPSC-CMs gradually showed mature structure as assessed by electron
      microscopy. Of note, X-ray diffraction identified 1,0 and 1,1 equatorial
      reflections attributable to myosin and actin-myosin lattice planes typical of
      organized cardiac muscle fibers within the transplanted cell sheets at 4 weeks,
      suggesting cyclic systolic myosin mass transfer to actin filaments in the
      transplanted iPSC-CMs. Transplantation of iPSC-CM cell sheets into the heart
      yielded functional and electrical recovery with cyclic contraction of
      transplanted cells in the rat MI heart, indicating that this strategy may be a
      promising cardiac muscle replacement therapy.

PMID- 25606822
TI  - Mental health care screening and care coordination during pregnancy and
      postpartum for women veterans.

PMID- 25606823
TI  - Integrating intimate partner violence assessment and intervention into healthcare
      in the United States: a systems approach.
AB  - The Institute of Medicine, United States Preventive Services Task Force (USPSTF),
      and national healthcare organizations recommend screening and counseling for
      intimate partner violence (IPV) within the US healthcare setting. The Affordable
      Care Act includes screening and brief counseling for IPV as part of required free
      preventive services for women. Thus, IPV screening and counseling must be
      implemented safely and effectively throughout the healthcare delivery system.
      Health professional education is one strategy for increasing screening and
      counseling in healthcare settings, but studies on improving screening and
      counseling for other health conditions highlight the critical role of making
      changes within the healthcare delivery system to drive desired improvements in
      clinician screening practices and health outcomes. This article outlines a
      systems approach to the implementation of IPV screening and counseling, with a
      focus on integrated health and advocacy service delivery to support
      identification and interventions, use of electronic health record (EHR) tools,
      and cross-sector partnerships. Practice and policy recommendations include (1)
      ensuring staff and clinician training in effective, client-centered IPV
      assessment that connects patients to support and services regardless of
      disclosure; (2) supporting enhancement of EHRs to prompt appropriate clinical
      care for IPV and facilitate capturing more detailed and standardized IPV data;
      and (3) integrating IPV care into quality and meaningful use measures. Research
      directions include studies across various health settings and populations,
      development of quality measures and patient-centered outcomes, and tests of
      multilevel approaches to improve the uptake and consistent implementation of
      evidence-informed IPV screening and counseling guidelines. 

PMID- 25606826
TI  - Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis
      through induction of autophagy in H9c2 cardiomyocytes.
AB  - Autophagy is a cellular self-catabolic process responsible for the degradation of
      proteins and organelles. Autophagy is able to promote cell survival in response
      to stress, and increased autophagy amongst cardiomyocytes has been identified in
      conditions of heart failure, starvation and ischemia/reperfusion. However, the
      detailed regulatory mechanisms underlying autophagy in heart disease have
      remained elusive. MicroRNAs (miRNAs) have been implicated in the regulation of
      autophagy in cells under stress. In the present study, the protective effect of
      miRNA (miR)-101 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis
      was investigated. It was revealed that H/R induced apoptosis in H9c2
      cardiomyocytes, accompanied by a downregulation of miR-101 expression. Further
      investigation identified Ras-related protein Rab-5A (RAB5A) as a direct target of
      miR-101. RAB5A was previously reported to be involved in autophagy; therefore,
      the present study further focused on the role of miR-101 in the regulation of
      autophagy under H/R and found that the inhibition of miR-101 attenuated H/R
      induced apoptosis, at least partially, via the induction of autophagy. In
      conclusion, the results of the present study revealed a beneficial effect of miR
      101 inhibition on H/R-induced apoptosis in cardiomyocytes, indicating that miR
      101 inhibition may present a potential therapeutic agent in the treatment or
      prevention of heart diseases.

PMID- 25606828
TI  - Impact factor: what is it and is it still relevant?

PMID- 25606829
TI  - Osteoradionecrosis of the temporal bone.

PMID- 25606827
TI  - Arthpyrones A-C, pyridone alkaloids from a sponge-derived fungus Arthrinium
      arundinis ZSDS1-F3.
AB  - Three new 4-hydroxy-2-pyridone alkaloids, arthpyrones A-C (1-3), were isolated
      from the sponge-derived fungus Arthrinium arundinis ZSDS1-F3. Their structures
      were elucidated on the basis of spectroscopic analysis, CD spectra, quantum
      chemical calculation, and X-ray single-crystal diffraction analysis. Compounds 1
      and 2 possessed a 2-pyridone core featured with a decalin moiety linked via a
      carboxide bridge bearing a novel oxabicyclo[3.3.1]nonane ring system rarely
      discovered in nature. A possible biosynthetic pathway for them was proposed. 

PMID- 25606824
TI  - Regulation of T-cell activation and migration by the kinase TBK1 during
      neuroinflammation.
AB  - Development of an immune or autoimmune response involves T-cell activation in
      lymphoid organs and subsequent migration to peripheral tissues. Here we show that
      T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes
      retention of effector T cells in the draining lymph node in a neuroinflammatory
      autoimmunity model, experimental autoimmune encephalomyelitis (EAE). At older
      ages, the T-cell-conditional TBK1-knockout mice also spontaneously accumulate T
      cells with activated phenotype. TBK1 controls the activation of AKT and its
      downstream kinase mTORC1 by a mechanism involving TBK1-stimulated AKT
      ubiquitination and degradation. The deregulated AKT-mTORC1 signalling in turn
      contributes to enhanced T-cell activation and impaired effector T-cell egress
      from draining lymph nodes. Treatment of mice with a small-molecule inhibitor of
      TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating
      T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling
      axis. 

PMID- 25606830
TI  - Arrested development: lingual thyroid gland.

PMID- 25606831
TI  - Cherubism.

PMID- 25606832
TI  - IgG4-related disease of the thyroid: a consideration in the differential
      diagnosis of an expanding thyroid mass.

PMID- 25606833
TI  - Contralateral hearing loss after vestibular schwannoma excision: a rare
      complication of neurotologic surgery.
AB  - We report a rare case of contralateral hearing loss after vestibular schwannoma
      excision in a 48-year-old man who underwent surgery via a suboccipital approach
      for removal of a nearly 2-cm lesion involving the right cerebellopontine angle.
      Postoperatively, the patient awoke with bilateral deafness, confirmed by both
      audiometry and spontaneous otoacoustic emissions. The patient was treated
      aggressively with high-dose intravenous steroids, vitamins E and C, and oxygen.
      Over the next several months he had gradual recovery of most of the hearing in
      his left (unoperated) ear. Contralateral hearing loss may develop after
      vestibular schwannoma excision; multiple pathophysiologic mechanisms for this
      occurrence have been proposed. 

PMID- 25606835
TI  - A case of myoepithelioma mimicking a parotid cyst.
AB  - Myoepithelioma is an uncommon tumor of the myoepithelial cells that is considered
      to represent a distinct category of tumor by the World Health Organization. It
      accounts for less than 1% of all tumors that develop in the salivary glands. We
      describe the case of a 35-year-old woman who presented to us with a painless
      swelling on the right side of her face. She was diagnosed with a parotid gland
      cyst by ultrasonography and computed tomography. Following excision of the mass,
      however, the pathology report identified the tumor as a solid myoepithelioma. To
      the best of our knowledge, this is the first reported case of a myoepithelioma
      that exhibited cystic features on radiologic examination even though it had a
      solid architecture. We also discuss the preoperative diagnostic aspects of the
      myoepitheliomas. 

PMID- 25606834
TI  - Effect of low-level laser therapy in the treatment of cochlear tinnitus: a double
      blind, placebo-controlled study.
AB  - Many treatments for chronic tinnitus have been attempted, but the condition
      remains difficult to cure, especially in the case of cochlear tinnitus. We
      conducted a prospective, double-blind, placebo-controlled study to assess the
      effect of low-dose laser therapy on chronic cochlear tinnitus. Our study
      population was made up of 66 patients-33 who received active laser treatment
      (case group) and 33 who received inactive dummy treatment (control group).
      Patients in the laser group received 5 mV with a wavelength of 650 nm for 20
      minutes a day, 5 days a week, for 4 weeks. The controls followed the same
      schedule, but they were "treated" with an inactive device. The degree of tinnitus
      was evaluated before and after treatment in each group in three ways: (1) the
      Tinnitus Severity Index (TSI), (2) a subjective 10-point self-assessment scale
      for tinnitus loudness, and (3) the Tinnitus Evaluation Test (TET). At study's
      end, we found no statistically significant differences between the case and
      control groups in the number of patients who experienced a reduction in TSI
      values (p = 0.589) or a reduction in subjective self-assessment scores (p =
      0.475). Nor did we find any significant reductions in the loudness (p = 0.665)
      and frequency (p = 0.396) of tinnitus as determined by the TET. We conclude that
      5-mV laser therapy with a wavelength of 650 nm is no better than placebo for
      improving hearing thresholds overall or for treating tinnitus with regard to age,
      sex, environmental noise level, and the duration of tinnitus. 

PMID- 25606837
TI  - Group A beta streptococcal infections in children after oral or dental trauma: a
      case series of 5 patients.
AB  - Group A streptococcus (GAS) produces a variety of disease processes in children.
      Severe invasive diseases such as necrotizing fasciitis can result. Traumatic
      dental injuries are common in the pediatric population, although the role of
      dental injuries in invasive GAS disease is not well characterized. In this
      article, we describe our retrospective series of 5 cases of GAS infection
      following oral or dental trauma in children. 

PMID- 25606839
TI  - A case of transient cortical blindness associated with hypercapnia as a result of
      extremely enlarged adenoid tissue.
AB  - Adenotonsillar hypertrophy is common among children, but it can lead to serious
      complications if left untreated. Among the well-known complications are
      obstructive sleep apnea syndrome, growth failure, cor pulmonale, and
      hypertension. One complication of adenotonsillar hypertrophy that has not been
      previously reported in the English-language literature is transient cortical
      blindness. We describe such a case, which occurred in a 6-year-old boy who
      presented with a sudden loss of vision and subsequent unconsciousness. He had
      experienced hypercapnia and was resuscitated via endotracheal tube ventilation.
      Laboratory and radiologic assessments found no pathology except for extremely
      enlarged adenoid tissue. Once the patient was stabilized, an urgent
      adenotonsillectomy was performed. The patient recovered well, and his vision and
      respiratory symptoms resolved. Severe hypertrophy of the adenoid tissue can cause
      hypercapnia and acidosis secondary to upper airway obstruction. The possibility
      of adenoid hypertrophy and hypercapnia should be kept in mind in cases of
      transient cortical blindness. Aggressive treatment, including early intubation
      and adenoidectomy, may lead to a rapid resolution of symptoms. 

PMID- 25606838
TI  - Spontaneous bilateral dural arteriovenous fistulas with pulsatile tinnitus.
AB  - Pulsatile tinnitus with normal otoscopic findings often presents a diagnostic
      challenge to otolaryngologists and can be attributed to serious vascular
      malformations such as dural arteriovenous fistulas (DAVFs). Spontaneous DAVFs are
      relatively rare. A 65-year-old woman presented with sudden-onset
      subjective/objective pulsatile tinnitus on the right side that had persisted for
      2 months. Angiography and magnetic resonance angiography revealed DAVF formation.
      Stereotactic radiosurgery was performed, and total remission of the DAVFs was
      achieved. 

PMID- 25606840
TI  - An uncommon cause of allergic fungal sinusitis: Rhizopus oryzae.
AB  - We report what we believe is the first case of allergic fungal rhinosinusitis
      (AFRS) caused by the fungus Rhizopus oryzae. Our patient was a 32-year-old woman
      who presented with unilateral nasal polyps and chronic nasal dysfunction.
      Computed tomography of the sinuses detected left-sided pansinusitis and bone
      erosion. T2-weighted magnetic resonance imaging demonstrated a signal void that
      suggested the presence of a fungal infection. The patient underwent unilateral
      ethmoidectomy. Histologic examination of the diseased tissue identified allergic
      mucin with 70% eosinophils and no fungal hyphae. Mycologic culture detected R
      oryzae. After a short period of improvement, the patient experienced a
      recurrence, which was confirmed by radiology. A second surgery was performed, and
      the same fungal hyphae were found in the mucus and on culture, which led us to
      suspect AFRS. Since no IgE test for R oryzae was available, we developed a
      specific immunologic assay that confirmed the presence of specific IgG, which
      identified a high degree of immunologic reaction against our homemade R oryzae
      antigens. With a long course of systemic antifungal treatment, the patient's
      symptoms resolved and no recurrence was noted at 5 years of follow-up. 

PMID- 25606841
TI  - Reconstructive and rehabilitation challenges following a cranio-orbital gunshot
      wound.
AB  - We present a case of a 26-year-old man who sustained a close-range gunshot wound
      to the head. His injuries included significant left orbital injury resulting in a
      ruptured, blind eye and severely comminuted fractures of the left orbital roof,
      superior and inferior orbital rims, and orbital floor. Associated injuries
      included left frontal lobe injury, anterior and posterior table fractures of the
      left frontal sinus, and a comminuted left zygomaticomaxillary complex fracture.
      We employed an interdisciplinary surgical approach with collaboration among the
      Otolaryngology, Neurosurgery, and Oculoplastic Surgery services performed in two
      stages. Management of such extensive craniofacial injuries can be challenging and
      requires a coordinated, interdisciplinary approach. 

PMID- 25606842
TI  - Bronchoscopic extraction of a chicken bone 5 years after aspiration.
AB  - A 58-year-old man with a remote history of choking on a chicken bone 5 years
      earlier presented with chronic cough but had no remarkable clinical examination
      findings. He was being followed for recurrent pneumonias complicated by a
      resistant empyema, for which he had undergone thoracotomy and decortication.
      Imaging studies initially missed a foreign body (the chicken bone), which was
      found on follow-up studies and was removed with a flexible bronchoscope despite
      the fact that 5 years had passed since the aspiration. 

PMID- 25606843
TI  - Glottic myxoma presenting as chronic dysphonia: a case report and review of the
      literature.
AB  - Myxomas of the vocal fold are rare benign tumors often presenting with chronic
      dysphonia and less frequently with airway obstruction. The current consensus is
      that all laryngeal myxomas should be totally excised with clear margins to
      prevent recurrences. The recommendation for complete excision, however, has to be
      balanced with consideration of preserving vocal fold phonatory and sphincteric
      function. We report a case of vocal fold myxoma recurring twice after subtotal
      excision via two surgical approaches. This case illustrates a benign lesion with
      potential for recurrence and the need for a balanced treatment approach. 

PMID- 25606844
TI  - Primary calcitonin-secreting neuroendocrine carcinoma of the supraglottic larynx.

PMID- 25606845
TI  - Unusual presentation of a midline neck mass.

PMID- 25606846
TI  - Endoscopic view of nasopharyngeal scarring.

PMID- 25606847
TI  - Metastatic squamous cell carcinoma of the tonsil presenting as otorrhea: a case
      report.
AB  - We describe the case of a 52-year-old man with a history of squamous cell
      carcinoma (SCC) of the tonsil who presented with right subacute otalgia and
      otorrhea. Dedicated computed tomography of the temporal bones showed
      opacification within the mastoid process with destruction of bony mastoid
      septations consistent with coalescent mastoiditis. Preoperative imaging showed no
      destruction or expansion of the bony eustachian tube that would indicate that a
      direct spread had occurred. An urgent cortical mastoidectomy was performed.
      Intraoperatively, a friable white mass surrounded with purulence and granulation
      tissue was biopsied and returned as SCC. The discrete metastasis was removed
      without complication. Postoperatively, the patient was prescribed palliative
      chemotherapy. This case shows that a metastatic SCC can be masked by an overlying
      mastoiditis, and thus it should be considered in the differential diagnosis of a
      patient with a history of oropharyngeal cancer. 

PMID- 25606848
TI  - Increased oxidative stress and disrupted small intestinal tight junctions in
      cigarette smoke-exposed rats.
AB  - Chronic obstructive pulmonary disease (COPD) is a major public health problem,
      and cigarette smoke (CS) is the primary risk factor. The pathology is often
      observed in the lung, but COPD is also associated with intestinal barrier
      disruption, although the underlying mechanisms are poorly understood. To address
      this, a CS-exposed rat model was evaluated in the present study by analyzing
      small intestinal gene expression using reverse transcription-quantitative
      polymerase chain reaction. CS exposure caused upregulation of the nicotinamide
      adenine dinucleotide phosphate-oxidase subunits nox2 and p22phox in the small
      intestine, while the antioxidative enzyme superoxide dismutase was downregulated.
      CS exposure also increased bax expression and decreased bcl-2 expression. This
      was associated with an elevation of hypoxia-inducible factor (HIF)-1alpha.
      Claudin-1 was decreased and claudin-2 increased, indicating a loosening of small
      intestinal tight junctions (TJs). These data suggest that during the development
      of COPD, HIF-1alpha expression is altered in the small intestine, which may be
      associated with the increased oxidative stress and apoptosis, eventually
      resulting in disruption of the intestinal TJs. 

PMID- 25606849
TI  - N-annulated perylene-substituted and fused porphyrin dimers with intense near
      infrared one-photon and two-photon absorption.
AB  - Fusion of two N-annulated perylene (NP) units with a fused porphyrin dimer along
      the S0-S1 electronic transition moment axis has resulted in new near-infrared
      (NIR) dyes 1 a/1 b with very intense absorption (epsilon>1.3*10(5) M(-1) cm(-1))
      beyond 1250 nm. Both compounds displayed moderate NIR fluorescence with
      fluorescence quantum yields of 4.4*10(-6) and 6.0*10(-6) for 1 a and 1 b,
      respectively. The NP-substituted porphyrin dimers 2 a/2 b have also been obtained
      by controlled oxidative coupling and cyclodehydrogenation, and they showed
      superimposed absorptions of the fused porphyrin dimer and the NP chromophore. The
      excited-state dynamics of all of these compounds have been studied by femtosecond
      transient absorption measurements, which revealed porphyrin dimer-like behaviour.
      These new chromophores also exhibited good nonlinear optical susceptibility with
      large two-photon absorption cross-sections in the NIR region due to extended pi
      conjugation. Time-dependent density functional theory calculations have been
      performed to aid our understanding of their electronic structures and absorption
      spectra.

PMID- 25606850
TI  - Nonlinear rheology of entangled polymers at turning point.
AB  - Thanks to extensive observations of strain localization upon startup or after
      stepwise shear, a conceptual framework for nonlinear rheology of entangled
      polymers appears to have emerged that has led to discovery of many new phenomena,
      which were not previously predicted by the standard tube model. On the other
      hand, the published theoretical and experimental attempts to test the limits of
      the tube model have largely demonstrated that the most experimental data appear
      consistent with the tube-model based theoretical calculations. Therefore, the
      field of nonlinear rheology of entangled polymers is at a turning point and is
      thus a rather crucial area in which further examinations are needed. In
      particular, more molecular dynamics simulations are needed to delineate the
      detailed molecular mechanisms for the various nonlinear rheological phenomena. 

PMID- 25606851
TI  - Real-time PCR demonstrates high prevalence of Schistosoma japonicum in the
      Philippines: implications for surveillance and control.
AB  - BACKGROUND: The Philippines has a population of approximately 103 million people,
      of which 6.7 million live in schistosomiasis-endemic areas with 1.8 million
      people being at risk of infection with Schistosoma japonicum. Although the
      country-wide prevalence of schistosomiasis japonica in the Philippines is
      relatively low, the prevalence of schistosomiasis can be high, approaching 65% in
      some endemic areas. Of the currently available microscopy-based diagnostic
      techniques for detecting schistosome infections in the Philippines and elsewhere,
      most exhibit varying diagnostic performances, with the Kato-Katz (KK) method
      having particularly poor sensitivity for detecting low intensity infections. This
      suggests that the actual prevalence of schistosomiasis japonica may be much
      higher than previous reports have indicated. METHODOLOGY/PRINCIPAL FINDINGS: Six
      barangay (villages) were selected to determine the prevalence of S. japonicum in
      humans in the municipality of Palapag, Northern Samar. Fecal samples were
      collected from 560 humans and examined by the KK method and a validated real-time
      PCR (qPCR) assay. A high S. japonicum prevalence (90.2%) was revealed using qPCR
      whereas the KK method indicated a lower prevalence (22.9%). The geometric mean
      eggs per gram (GMEPG) determined by the qPCR was 36.5 and 11.5 by the KK. These
      results, particularly those obtained by the qPCR, indicate that the prevalence of
      schistosomiasis in this region of the Philippines is much higher than
      historically reported. CONCLUSIONS/SIGNIFICANCE: Despite being more expensive,
      qPCR can complement the KK procedure, particularly for surveillance and
      monitoring of areas where extensive schistosomiasis control has led to low
      prevalence and intensity infections and where schistosomiasis elimination is on
      the horizon, as for example in southern China.

PMID- 25606853
TI  - Resistance patterns among multidrug-resistant tuberculosis patients in greater
      metropolitan Mumbai: trends over time.
AB  - BACKGROUND: While the high burden of multidrug-resistant tuberculosis (MDR-TB)
      itself is a matter of great concern, the emergence and rise of advanced forms of
      drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug
      resistant TB (XXDR-TB) is more troubling. The aim of this study was to
      investigate the trends over time of patterns of drug resistance in a sample of
      MDR-TB patients in greater metropolitan Mumbai, India. METHODS: This was a
      retrospective, observational study of drug susceptibility testing (DST) results
      among MDR-TB patients from eight health care facilities in greater Mumbai between
      2005 and 2013. We classified resistance patterns into four categories: MDR-TB,
      pre-XDR-TB, XDR-TB and XXDR-TB. RESULTS: A total of 340 MDR-TB patients were
      included in the study. Pre-XDR-TB was the most common form of drug-resistant TB
      observed overall in this Mumbai population at 56.8% compared to 29.4% for MDR-TB.
      The proportion of patients with MDR-TB was 39.4% in the period 2005-2007 and
      27.8% in 2011-2013, while the proportion of those with XDR-TB and XXDR-TB was
      changed from 6.1% and 0% respectively to 10.6% and 5.6% during the same time
      period. During the same periods, the proportions of patients with ofloxacin,
      moxifloxacin and ethionamide resistance significantly increased from 57.6% to
      75.3%, from 60.0% to 69.5% and from 24.2% to 52.5% respectively (p<0.05).
      DISCUSSION: The observed trends in TB drug-resistance patterns in Mumbai
      highlight the need for individualized drug regimens, designed on the basis of DST
      results involving first- and second-line anti-TB drugs and treatment history of
      the patient. A drug-resistant TB case-finding strategy based on molecular
      techniques that identify only rifampicin resistance will lead to initiation of
      suboptimal treatment regimens for a significant number of patients, which may in
      turn contribute to amplification of resistance and transmission of strains with
      increasingly advanced resistance within the community.

PMID- 25606854
TI  - A permutation method to assess heterogeneity in external validation for risk
      prediction models.
AB  - The value of a developed prediction model depends on its performance outside the
      development sample. The key is therefore to externally validate the model on a
      different but related independent data. In this study, we propose a permutation
      method to assess heterogeneity in external validation for risk prediction models.
      The permutation p value measures the extent of homology between development and
      validation datasets. If p < 0.05, the model may not be directly transported to
      the external validation population without further revision or updating. Monte
      Carlo simulations are conducted to evaluate the statistical properties of the
      proposed method, and two microarray breast cancer datasets are analyzed for
      demonstration. The permutation method is easy to implement and is recommended for
      routine use in external validation for risk prediction models. 

PMID- 25606852
TI  - Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that
      selectively activates the MAPK/ERK pathway.
AB  - The alpha1A-AR is thought to couple predominantly to the Galphaq/PLC pathway and
      lead to phosphoinositide hydrolysis and calcium mobilization, although certain
      agonists acting at this receptor have been reported to trigger activation of
      arachidonic acid formation and MAPK pathways. For several G protein-coupled
      receptors (GPCRs) agonists can manifest a bias for activation of particular
      effector signaling output, i.e., not all agonists of a given GPCR generate
      responses through utilization of the same signaling cascade(s). Previous work
      with Galphaq coupling-defective variants of alpha1A-AR, as well as a combination
      of Ca2+ channel blockers, uncovered cross-talk between alpha1A-AR and beta2-AR
      that leads to potentiation of a Galphaq-independent signaling cascade in response
      to alpha1A-AR activation. We hypothesized that molecules exist that act as biased
      agonists to selectively activate this pathway. In this report, isoproterenol
      (Iso), typically viewed as beta-AR-selective agonist, was examined with respect
      to activation of alpha1A-AR. alpha1A-AR selective antagonists were used to
      specifically block Iso evoked signaling in different cellular backgrounds and
      confirm its action at alpha1A-AR. Iso induced signaling at alpha1A-AR was further
      interrogated by probing steps along the Galphaq /PLC, Galphas and MAPK/ERK
      pathways. In HEK-293/EBNA cells transiently transduced with alpha1A-AR, and
      CHO_alpha1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+
      mobilization that could be blocked by alpha1A-AR selective antagonists. The
      kinetics of Iso induced Ca2+ transients differed from typical Galphaq- mediated
      Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained
      phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could
      be detected in either cell line after stimulation with Iso, but activation was
      accompanied by receptor internalization. Data are presented that indicate that
      Iso represents a novel type of alpha1A-AR partial agonist with signaling bias
      toward MAPK/ERK signaling cascade that is likely independent of coupling to
      Galphaq.

PMID- 25606857
TI  - Correction: Contribution for the Derivation of a Soil Screening Value (SSV) for
      Uranium, Using a Natural Reference Soil.

PMID- 25606856
TI  - Characterization of the factors that influence sinapine concentration in rapeseed
      meal during fermentation.
AB  - We analyzed and compared the difference in sinapine concentration in rapeseed
      meal between the filamentous fungus, Trametes sp 48424, and the yeast,
      Saccharomyces cerevisiae, in both liquid and solid-state fermentation. During
      liquid and solid-state fermentation by Trametes sp 48424, the sinapine
      concentration decreased significantly. In contrast, the liquid and solid-state
      fermentation process by Saccharomyces cerevisiae just slightly decreased the
      sinapine concentration (P <= 0.05). After the solid-state fermented samples were
      dried, the concentration of sinapine in rapeseed meal decreased significantly in
      Saccharomyces cerevisiae. Based on the measurement of laccase activity, we
      observed that laccase induced the decrease in the concentration of sinapine
      during fermentation with Trametes sp 48424. In order to eliminate the influence
      of microorganisms and the metabolites produced during fermentation, high moisture
      rapeseed meal and the original rapeseed meal were dried at 90  degrees C and 105 
      degrees C, respectively. During drying, the concentration of sinapine in high
      moisture rapeseed meal decreased rapidly and we obtained a high correlation
      coefficient between the concentration of sinapine and loss of moisture. Our
      results suggest that drying and enzymes, especially laccase that is produced
      during the solid-state fermentation process, may be the main factors that affect
      the concentration of sinapine in rapeseed meal.

PMID- 25606858
TI  - Forearm position's alteration of radial-head impingement on wrist-extensor
      tendons.
AB  - CONTEXT: Lateral epicondylalgia, pain at the lateral elbow, is commonly
      associated with extensor carpi radialis brevis tendinopathy. The radial head,
      which abuts the extensor tendons and is elliptical in shape, may affect the
      extensor tendons during pronation of the forearm. Cadaverous studies have shown
      that the radial head may act as a cam in pronation, to offer a mechanical
      advantage to the common extensor tendon and to mitigate load on the origin of the
      extensor carpi radialis brevis tendon. OBJECTIVE: To determine the effect of
      radial-head position on the wrist-extensor tendons in vivo. DESIGN: Repeated
      measures design. SETTING: Laboratory. PARTICIPANTS: 22 participants (12 male, 2
      left-handed). MAIN OUTCOME MEASURES: Distance (mm) from subcutaneous fascia to
      radial head measured by ultrasound. RESULTS: The radial head in supination was
      significantly deeper than either pronation or midprone, indicating a smaller cam
      effect in supination. CONCLUSION: The authors recommend that the effect of radial
      head position and its relationship to the area of tendon pathology be considered
      clinically in the rehabilitation of patients suffering from lateral
      epicondylalgia.

PMID- 25606859
TI  - The validity of the nordic hamstring lower for a field-based assessment of
      eccentric hamstring strength.
AB  - CONTEXT: Hamstring injury-risk assessment has primarily been investigated using
      isokinetic dynamometry. However, practical issues such as cost and availability
      limit the widespread application of isokinetics for injury-risk assessment; thus,
      field-based alternatives for assessing eccentric hamstring strength are needed.
      OBJECTIVE: The aim of this study was to investigate the validity of the angle
      achieved during Nordic hamstring lowers (break-point angle) as a field-based test
      for eccentric hamstring strength. DESIGN: Exploratory study. SETTING: Laboratory.
      PARTICIPANTS: Sixteen male (n = 7) and female (n = 9) soccer players (mean +/- SD
      age 24 +/- 6 y, height 1.77 +/- 0.12 m, and body mass 68.5 +/- 16.5 kg) acted as
      subjects for the study. MAIN OUTCOME MEASURES: The authors explored relationships
      between the Nordic break-point angle (the point at which the subject can no
      longer resist the increasing gravitational moment during a Nordic hamstring
      lower) measured from video and isokinetic peak torque and angle of peak torque of
      right- and left-knee flexors. RESULTS: The results revealed a meaningful
      relationship between eccentric knee-flexor peak torque (average of right and left
      limbs) and the Nordic break-point angle (r = -.808, r2 = 65%, P < .00001).
      However, there was a weak relationship observed (r = .480, r2 = 23%, P = .06)
      between break-point angle and the angle of peak torque (average of right and left
      limbs). CONCLUSIONS: The results suggest that the break-point angle achieved
      during Nordic hamstring lowers could be used as a field-based assessment of
      eccentric hamstring strength.

PMID- 25606860
TI  - The effectiveness of whole-body-vibration training in improving hamstring
      flexibility in physically active adults.
AB  - CLINICAL SCENARIO: Hamstring tightness is common among physically active
      individuals. In addition to limiting range of motion and increasing the risk of
      muscle strain, hamstring tightness contributes to a variety of orthopedic
      conditions. Therefore, clinicians continue to identify effective methods to
      increase flexibility. Although hamstring tightness is typically treated with
      common stretching techniques such as static stretching and proprioceptive
      neuromuscular facilitation, it has been suggested that whole-body-vibration (WBV)
      training may improve hamstring flexibility. CLINICAL QUESTION: Can WBV training,
      used in isolation or in combination with common stretching protocols or exercise,
      improve hamstring flexibility in physically active young adults? Summary of Key
      Findings: Of the included studies, 4 demonstrated statistically significant
      improvements in hamstring flexibility in the intervention group, and 1 study
      found minor improvements over time in the intervention group after treatment.
      Clinical Bottom Line: There is moderate evidence to support the use of WBV
      training to improve hamstring flexibility in physically active young adults.
      STRENGTH OF RECOMMENDATION: There is grade B evidence that WBV training improves
      hamstring flexibility in physically active adults. The Centre of Evidence Based
      Medicine recommends a grade of B for level 2 evidence with consistent findings.

PMID- 25606855
TI  - Analysis of putative apoplastic effectors from the nematode, Globodera
      rostochiensis, and identification of an expansin-like protein that can induce and
      suppress host defenses.
AB  - The potato cyst nematode, Globodera rostochiensis, is an important pest of
      potato. Like other pathogens, plant parasitic nematodes are presumed to employ
      effector proteins, secreted into the apoplast as well as the host cytoplasm, to
      alter plant cellular functions and successfully infect their hosts. We have
      generated a library of ORFs encoding putative G. rostochiensis putative
      apoplastic effectors in vectors for expression in planta. These clones were
      assessed for morphological and developmental effects on plants as well as their
      ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins
      induced developmental phenotypes, whereas predicted cell wall-modifying proteins
      induced necrosis and chlorosis, consistent with roles in cell fate alteration and
      tissue invasion, respectively. When directed to the apoplast with a signal
      peptide, two effectors, an ubiquitin extension protein (GrUBCEP12) and an
      expansin-like protein (GrEXPB2), suppressed defense responses including NB-LRR
      signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in
      species- and sequence-specific manner. Our results are consistent with the
      scenario whereby potato cyst nematodes secrete effectors that modulate host cell
      fate and metabolism as well as modifying host cell walls. Furthermore, we show a
      novel role for an apoplastic expansin-like protein in suppressing intra-cellular
      defense responses. 

PMID- 25606863
TI  - Crystal field analysis of Dy and Tm implanted silicon for photonic and quantum
      technologies.
AB  - We report the lattice site and symmetry of optically active Dy<sup>3+</sup> and
      Tm<sup>3+</sup> implanted Si. Local symmetry was determined by fitting crystal
      field parameters (CFPs), corresponding to various common symmetries, to the
      ground state splitting determined by photoluminescence measurements. These CFP
      values were then used to calculate the splitting of every J manifold. We find
      that both Dy and Tm ions are in a Si substitution site with local tetragonal
      symmetry. Knowledge of rare-earth ion symmetry is important in maximising the
      number of optically active centres and for quantum technology applications where
      local symmetry can be used to control decoherence. 

PMID- 25606864
TI  - Widely tunable single bandpass microwave photonic filter based on Brillouin
      assisted optical carrier recovery.
AB  - A widely tunable single bandpass microwave photonic filter (MPF) based on
      Brillouin-assisted optical carrier recovery in a highly nonlinear fiber (HNLF)
      with only one optical filter is proposed and experimentally demonstrated. The
      fundamental principle lies in the fact that the suppressed optical carrier of the
      phase modulated optical signal could be recovered by the stimulated Brillouin
      scattering (SBS) amplification effect. When phase modulated optical signals go
      through an optical filter with a bandpass response, the optical carrier and the
      upper sidebands suffer from the suppression of the optical filter because they
      fall in the stopband of that. In our system, the optical carrier could be
      recovered by the SBS operation around 38 dB. The MPF is achieved by one-to-one
      mapping from the optical domain to the electrical domain only when one of phase
      modulated sidebands lies in the bandpass of the optical filter. It shows an
      excellent selectivity with a 3-dB bandwidth of 170 MHz over a tuning frequency
      range of 9.5-32.5 GHz. The out-of-band suppression of the MPF is more than 20 dB.
      Moreover, the MPF shows an excellent shape factor with 10-dB bandwidth of only
      520 MHz. The frequency response of the MPF could be widely tuned by changing the
      frequency difference between the frequency of the optical carrier and the center
      frequency of the bandpass of the optical filter. A proof-of-concept experiment is
      carried out to verify the proposed approach. 

PMID- 25606865
TI  - Linear dissipative soliton in an anomalous-dispersion fiber laser.
AB  - We report on the generation of linear dissipative soliton (LDS) from an erbium
      doped actively mode-locked fiber laser. We show that depending on the down
      chirping effect of quadratic phase modulation, instead of the fiber nonlinear
      Kerr effect in an all-normal-dispersion (ANDi) cavity, stable LDS can be realized
      in the linear dissipative system. The DS operation of ANDi laser and LDS
      operation of anomalous dispersion laser are experimentally investigated and
      compared, and the formation mechanisms of the DS and LDS are discussed. Finally,
      optical frequency comb generated by the LDS laser is demonstrated. 

PMID- 25606866
TI  - Mode multi/demultiplexing with parallel waveguide for mode division multiplexed
      transmission.
AB  - We propose a planar lightwave circuit (PLC)-based mode multi/demultiplexer
      (MUX/DEMUX) with an asymmetric parallel waveguide for mode division multiplexed
      (MDM) transmission. The PLCb-ased mode MUX/DEMUX has advantage of selectively
      exciting higher-order mode. We realize three-mode (LP(01), LP(11)a, and LP(21)a)
      multiplexing by using an asymmetric parallel waveguide. We then design and
      fabricate a PLC-based mode MUX/DEMUX on one chip by using our proposed LP(11)
      mode rotator to allow us to utilize the LP(11)b mode. We successfully multiplex
      the LP(01), LP(11)a, and LP(11)b modes and achieve a relatively low insertion
      loss over the C-band using our fabricated mode MUX/DEMUX. Our results indicate
      that the PLC-based mode MUX/DEMUX with a uniform height has the potential to
      increase the mode number by using an LP(11)b mode.

PMID- 25606867
TI  - Enhanced performance of 400 Gb/s DML-based CAP systems using optical filtering
      technique for short reach communication.
AB  - A parallel transmission approach is more likely to realize 400 Gb/s and above
      short reach transmission as it helps to reduce the cost of both electrical and
      optical device largely. Directly modulated lasers (DML) are more attractive in
      400 Gb/s approach, because it requires relatively small amount of driving power
      and has low insertion loss, thus lowering its cost. However, the intrinsic chirp
      will degrade the transmission performance. In this paper, an optical filtering
      technique is introduced for 400 Gb/s high-speed DML-based carrierless amplitude
      and phase (CAP) modulation short reach systems for the first time. Owing to the
      additional optical filter, 1 dB and 3.6 dB sensitivity improvement at BER of 3.8
      x 10(-3) is obtained for the back-to-back and 15 km fiber link transmission for
      single lane at the bitrate of 28 Gb/s. Then a 16-lane CAP16 system with a total
      bit rate of 413 Gb/s is demonstrated experimentally using low-cost 10 GHz-class
      DML using optical filtering technique.

PMID- 25606868
TI  - Flat lens criterion by small-angle phase.
AB  - We show that a classical imaging criterion based on angular dependence of small
      angle phase can be applied to any system composed of planar, uniform media to
      determine if it is a flat lens capable of forming a real paraxial image and to
      estimate the image location. The real paraxial image location obtained by this
      method shows agreement with past demonstrations of far-field flat-lens imaging
      and can even predict the location of super-resolved images in the near-field. The
      generality of this criterion leads to several new predictions: flat lenses for
      transverse-electric polarization using dielectric layers, a broadband flat lens
      working across the ultraviolet-visible spectrum, and a flat lens configuration
      with an image plane located up to several wavelengths from the exit surface.
      These predictions are supported by full-wave simulations. Our work shows that
      small-angle phase can be used as a generic metric to categorize and design flat
      lenses. 

PMID- 25606869
TI  - Stabilization of microwave signal generated by a dual-polarization DBR fiber
      laser via optical feedback.
AB  - Microwave signals can be generated by beating the two orthogonal polarization
      modes from a dual-frequency fiber grating laser. In this paper, we present that
      the phase noise of the microwave signal can be significantly reduced via optical
      feedback by cascading an external cavity. This is achieved as a result of the
      bandwidth narrowing of each polarization laser mode when introducing phase
      matched feedbacks into the laser cavity. By optimizing the external cavity length
      and the feedback ratio, the noise level over low frequencies has been reduced by
      up to 30 dB, from -42 to -72 dBc/Hz at 1 kHz, and from -72 to -102 dBc/Hz at 10
      kHz. Meanwhile the relaxation resonant peaks can be eliminated. Compared with the
      existing techniques, the present method can offer a cost-effective, low-noise
      microwave signal, without the requirement for complex electrical feedback system.

PMID- 25606870
TI  - Transmission grating stretcher for contrast enhancement of high power lasers.
AB  - We propose, for the first time, a transmission grating stretcher for high power
      lasers and demonstrate its superiority over conventional, reflective gold grating
      stretchers in terms of pulse temporal quality. We show that, compared to a
      conventional stretcher with the same stretching factor, the transmission-grating
      based stretcher yields more than an order of magnitude improvement in the
      contrast pedestal. We have also quantitatively characterized the roughness of the
      grating surfaces and estimated its impact on the contrast pedestal. 

PMID- 25606871
TI  - Atomic mercury vapor inside a hollow-core photonic crystal fiber.
AB  - We demonstrate high atomic mercury vapor pressure in a kagome-style hollow-core
      photonic crystal fiber at room temperature. After a few days of exposure to
      mercury vapor the fiber is homogeneously filled and the optical depth achieved
      remains constant. With incoherent optical pumping from the ground state we
      achieve an optical depth of 114 at the 6(3)P(2) - 6(3)D(3) transition,
      corresponding to an atomic mercury number density of 6 * 10(10) cm(-3). The use
      of mercury vapor in quasi one-dimensional confinement may be advantageous
      compared to chemically more active alkali vapor, while offering strong optical
      nonlinearities in the ultraviolet region of the optical spectrum.

PMID- 25606872
TI  - Widely tunable SPP bandgap in a nonlinear metal-insulator-metal waveguide.
AB  - In this article, we propose a novel kind of widely tunable surface plasmon
      polaritons (SPP) bandgap in a Kerr nonlinear metal-insulator-metal waveguide. By
      two identical gratings, the pump beam is coupled to two opposing SPP waves, which
      interfere with each other and results in SPP standing wave in the region between
      the two gratings. The refractive index of the Kerr nonlinear material is then
      periodically modulated by the SPP standing wave, and a SPP bandgap is formed. The
      position of the SPP bandgap can be tuned from 1.4 MUm to 1.75 MUm by adjusting
      the pump wavelength, and the relationship between the transmittance contrast of
      the bandgap and the pump power is also studied. Comparing with existing methods
      that directly modulate the refractive index (RI) or the width of the waveguide,
      in our work, the periodic modulation of the RI comes from the interference of the
      pump light, which can greatly simplify the fabrication. This work may find
      applications in the design of novel nonlinear devices for future all-optical
      integrated circuits. 

PMID- 25606873
TI  - Process dependence of morphology and microstructure of cyanine dye J-aggregate
      film: correlation with absorption, photo- and electroluminescence properties.
AB  - Cyanine dye J-aggregate films are a class of absorbing and luminescent materials
      which have been extensively applied in the polariton-based research. Here we
      systematically study the DEDOC cyanine dyes J-aggregate films made by layer-by
      layer assembly and spin-coating processes to establish a clear correlation
      between the film structure and the absorption and luminescence properties. From
      detailed analyses of morphology, optical spectra, and light-emitting diode
      characteristics, we demonstrate that layer-by-layer assembled film has higher
      degrees of homogeneity and molecular packing quality than spin-coated film,
      leading to a higher absorption coefficient, more uniform luminescence, and a
      greater electroluminescence quantum efficiency with maximized thickness. 

PMID- 25606874
TI  - High performance wafer-fused semiconductor disk lasers emitting in the 1300 nm
      waveband.
AB  - We report for the first time on the performance of 1300 nm waveband semiconductor
      disc lasers (SDLs) with wafer fused gain mirrors that implement intracavity
      diamond and flip-chip heat dissipation schemes based on the same gain material.
      With a new type of gain mirror structure, maximum output power values reach 7.1 W
      with intracavity diamond gain mirrors and 5.6 W with flip-chip gain mirrors,
      using a pump spot diameter of 300 um, exhibiting a beam quality factor M(2)< 1.25
      in the full operation range. These results confirm previously published
      theoretical modeling of these types of SDLs.

PMID- 25606875
TI  - Optical injection locking of monolithically integrated photonic source for
      generation of high purity signals above 100 GHz.
AB  - A monolithically integrated photonic source for tuneable mm-wave signal
      generation has been fabricated. The source consists of 14 active components, i.e.
      semiconductor lasers, amplifiers and photodetectors, all integrated on a 3 mm(2)
      InP chip. Heterodyne signals in the range between 85 GHz and 120 GHz with up to 
      10 dBm output power have been successfully generated. By optically injection
      locking the integrated lasers to an external optical comb source, high-spectral
      purity signals at frequencies >100 GHz have been generated, with phase noise
      spectral density below -90 dBc/Hz being achieved at offsets from the carrier
      greater than 10 kHz.

PMID- 25606876
TI  - Simultaneous multichannel wavelength multicasting and XOR logic gate multicasting
      for three DPSK signals based on four-wave mixing in quantum-dot semiconductor
      optical amplifier.
AB  - In this paper, we experimentally demonstrate simultaneous multichannel wavelength
      multicasting (MWM) and exclusive-OR logic gate multicasting (XOR-LGM) for three
      10Gbps non-return-to-zero differential phase-shift-keying (NRZ-DPSK) signals in
      quantum-dot semiconductor optical amplifier (QD-SOA) by exploiting the four-wave
      mixing (FWM) process. No additional pump is needed in the scheme. Through the
      interaction of the input three 10Gbps DPSK signal lights in QD-SOA, each channel
      is successfully multicasted to three wavelengths (1-to-3 for each), totally 3-to
      9 MWM, and at the same time, three-output XOR-LGM is obtained at three different
      wavelengths. All the new generated channels are with a power penalty less than
      1.2dB at a BER of 10(-9). Degenerate and non-degenerate FWM components are fully
      used in the experiment for data and logic multicasting.

PMID- 25606877
TI  - Quadrature demultiplexing using a degenerate vector parametric amplifier.
AB  - We report on quadrature demultiplexing of a quadrature phase-shift keying (QPSK)
      signal into two cross-polarized binary phase-shift keying (BPSK) signals with
      negligible penalty at bit-error rate (BER) equal to 10(-9). The all-optical
      quadrature demultiplexing is achieved using a degenerate vector parametric
      amplifier operating in phase-insensitive mode. We also propose and demonstrate
      the use of a novel and simple phase-locked loop (PLL) scheme based on detecting
      the envelope of one of the signals after demultiplexing in order to achieve
      stable quadrature decomposition.

PMID- 25606878
TI  - Gap solitons in PT-symmetric optical lattices with higher-order diffraction.
AB  - The existence and stability of gap solitons are investigated in the semi-infinite
      gap of a parity-time (PT)-symmetric periodic potential (optical lattice) with a
      higher-order diffraction. The Bloch bands and band gaps of this PT-symmetric
      optical lattice depend crucially on the coupling constant of the fourth-order
      diffraction, whereas the phase transition point of this PT optical lattice
      remains unchangeable. The fourth-order diffraction plays a significant role in
      destabilizing the propagation of dipole solitons. Specifically, when the fourth
      order diffraction coupling constant increases, the stable region of the dipole
      solitons shrinks as new regions of instability appear. However, fundamental
      solitons are found to be always linearly stable with arbitrary positive value of
      the coupling constant. We also investigate nonlinear evolution of the PT solitons
      under perturbation. 

PMID- 25606879
TI  - Optical properties of plasmonic light-emitting diodes based on flip-chip III
      nitride core-shell nanowires.
AB  - In this work, we utilize the finite difference time domain (FDTD) method to
      investigate the Purcell factor, light extraction efficiency (EXE), and cavity
      quality parameter (Q), and to predict the modulation response of Ag-clad flip
      chip GaN/InGaN core-shell nanowire light-emitting diodes (LEDs) with the
      potential for electrical injection. We consider the need for a pn-junction, the
      effects of the substrate, and the limitations of nanoscale fabrication techniques
      in the evaluation. The investigated core-shell nanowire consists of an n-GaN
      core, surrounded by nonpolar m-plane quantum wells, p-GaN, and silver cladding
      layers. The core-shell nanowire geometry exhibits a Purcell factor of 57,
      resulting in a predicted limit of 30 GHz for the 3dB modulation bandwidth. 

PMID- 25606880
TI  - High-performance TDM demultiplexing of coherent Nyquist pulses using time-domain
      orthogonality.
AB  - We propose a simple and high-performance scheme for demultiplexing coherent
      Nyquist TDM signals by photo-mixing on a photo-detector with Nyquist LO pulses.
      This scheme takes advantage of the time-domain orthogonality of Nyquist pulses,
      which enables high-SNR demultiplexing and homodyne detection simultaneously in
      spite of a strong overlap with adjacent pulses in the time domain. The
      feasibility of this scheme is demonstrated through a demultiplexing experiment
      employing 80 Gbaud, 64 QAM Nyquist pulse OTDM signals. This scheme exhibits
      excellent demultiplexing performance with a much simpler configuration than a
      conventional ultrafast all-optical sampling scheme. 

PMID- 25606881
TI  - Paraxial ray optics cloaking.
AB  - Despite much interest and progress in optical spatial cloaking, a three
      dimensional (3D), transmitting, continuously multidirectional cloak in the
      visible regime has not yet been demonstrated. Here we experimentally demonstrate
      such a cloak using ray optics, albeit with some edge effects. Our device requires
      no new materials, uses isotropic off-the-shelf optics, scales easily to cloak
      arbitrarily large objects, and is as broadband as the choice of optical material,
      all of which have been challenges for current cloaking schemes. In addition, we
      provide a concise formalism that quantifies and produces perfect optical cloaks
      in the small-angle ('paraxial') limit. 

PMID- 25606882
TI  - Spatially tunable photonic bandgap of wide spectral range and lasing emission
      based on a blue phase wedge cell.
AB  - This study demonstrates for the first time a continuously tunable photonic
      bandgap (PBG) of wide spectral range based on a blue phase (BP) wedge cell. A
      continuously shifting PBG of the BP wedge cell occurs due to the thickness
      gradient of the wedge cell at a fixed temperature. The wedge cell provides a
      gradient of boundary force on the LCs and thus forms a distribution of BP crystal
      structure with a gradient lattice. Additionally, a spatially tunable lasing
      emission based on a dye-doped BP (DDBP) wedge cell is also demonstrated. The
      tunable band of the PBG and lasing emission is about 130 nm and 70 nm,
      respectively, which tuning spectral ranges are significantly wider than those of
      CLC and DDCLC wedge cells, respectively. Such a BP device has a significant
      potential in applications of tunable photonic devices and displays. 

PMID- 25606883
TI  - Fabrication, splicing, Bragg grating writing, and polyelectrolyte
      functionalization of exposed-core microstructured optical fibers.
AB  - Femtosecond laser written Bragg gratings have been written in exposed-core
      microstructured optical fibers with core diameters ranging from 2.7 um to 12.5 um
      and can be spliced to conventional single mode fiber. Writing a Bragg grating on
      an open core fiber allows for real-time refractive index based sensing, with a
      view to multiplexed biosensing. Smaller core fibers are shown both experimentally
      and theoretically to provide a higher sensitivity. A 7.5 um core diameter fiber
      is shown to provide a good compromise between sensitivity and practicality and
      was used for monitoring the deposition of polyelectrolyte layers, an important
      first step in developing a biosensor. 

PMID- 25606884
TI  - Pre-plasma formation in experiments using petawatt lasers.
AB  - We used time-resolved shadowgraphy to characterize the pre-plasma formation in
      solid-target interaction experiments with micrometer-scale accuracy. We performed
      quantitative measurements of the plasma density for amplified spontaneous
      emission (ASE) levels ranging from 2 . 10(-7) to 10(-10) backed with 2
      dimensional hydrodynamic simulations. We find that ASE levels above 10(-9) are
      able to create a significant pre-plasma plume that features a plasma canal
      driving a self-focusing of the laser beam. For ASE levels of 10(-10), no ASE pre
      plasma could be detected.

PMID- 25606885
TI  - Image quality enhancement using original lens via optical computing.
AB  - High-end lenses are usually composed of many optical elements to compensate
      various optical aberrations, e.g. geometric distortion, monochromatic and
      chromatic aberrations. The resulting complexity and machining accuracy
      requirements make high-end lenses too expensive, heavy, and fragile for day-to
      day photography. To address this problem, we devised an optical computing
      approach to touch-up the low quality photos produced by simpler lenses. We
      propose a setup consisting of an easily accessible display and the original
      camera in order to perform optical aberration correction with a deconvolution
      framework. The equivalence of the degeneration model and the lens's optical
      computing turns the traditional blind deconvolution algorithm into its non-blind
      counterpart and promises robust performance. A prototype system is implemented to
      verify the feasibility of the proposed method, and a series of experiments on
      both synthetic and captured images are applied to demonstrate effectiveness and
      performance. 

PMID- 25606886
TI  - Enhanced learning-based imaging with thin-film luminescent concentrators.
AB  - LumiConSense, a transparent, flexible, scalable, and disposable thin-film image
      sensor has the potential to lead to new human-computer interfaces that are
      unconstrained in shape and sensing-distance. In this article we make four new
      contributions: (1) A new real-time image reconstruction method that results in a
      significant enhancement of image quality compared to previous approaches; (2) the
      efficient combination of image reconstruction and shift-invariant linear image
      processing operations; (3) various hardware and software prototypes which,
      realize the above contributions, demonstrating the current potential of our
      sensor for real-time applications; and finally, (4) a further higher quality
      offline reconstruction algorithm. 

PMID- 25606887
TI  - Observation of the four wave mixing photonic band gap signal in
      electromagnetically induced grating.
AB  - For the first time, we experimentally and theoretically research about the probe
      transmission signal (PTS), the reflected four wave mixing band gap signal(FWM
      BGS) and fluorescence signal (FLS) under the double dressing effect in an
      inverted Y-type four level system. FWM BGS results from photonic band gap
      structure. We demonstrate that the characteristics of PTS, FWM BGS and FLS can be
      controlled by power, phase and the frequency detuning of the dressing beams. It
      is observed in our experiment that FWM BGS switches from suppression to
      enhancement, corresponding to the switch from transmission enhancement to
      absorption enhancement in the PTS with changing the relative phase. We also
      observe the relation among the three signals, which satisfy the law of
      conservation of energy. Such scheme could have potential applications in optical
      diodes, amplifiers and quantum information processing. 

PMID- 25606888
TI  - Picometer-scale surface roughness measurements inside hollow glass fibres.
AB  - A differential profilometry technique is adapted to the problem of measuring the
      roughness of hollow glass fibres by use of immersion objectives and index
      matching liquid. The technique can achieve picometer level sensitivity. Cross
      validation with AFM measurements is obtained through use of vitreous silica step
      calibration samples. Measurements on the inner surfaces of fibre-sized glass
      capillaries drawn from high purity suprasil F300 tubes show a sub-nanometer
      roughness, and the roughness power spectrum measured in the range [5 . 10(-3) m(
      1) 10(-1) m(-1)] is consistent with the description of the glass surface as a
      superposition of frozen capillary waves. The surface roughness spectrum of two
      capillary tubes of differing compositions can be quantitatively distinguished.

PMID- 25606889
TI  - Mitigation of organic laser damage precursors from chemical processing of fused
      silica.
AB  - Increases in the laser damage threshold of fused silica have been driven by the
      successive elimination of near-surface damage precursors such as polishing
      residue, fractures, and inorganic salts. In this work, we show that trace
      impurities in ultrapure water used to process fused silica optics may be
      responsible for the formation of carbonaceous deposits. We use surrogate
      materials to show that organic compounds precipitated onto fused silica surfaces
      form discrete damage precursors. Following a standard etching process, solvent
      free oxidative decomposition using oxygen plasma or high-temperature thermal
      treatments in air reduced the total density of damage precursors to as low as <50
      cm(-2). Finally, we show that inorganic compounds are more likely to cause damage
      when they are tightly adhered to a surface, which may explain why high
      temperature thermal treatments have been historically unsuccessful at removing
      extrinsic damage precursors from fused silica.

PMID- 25606890
TI  - Enhanced single-stage laser-driven electron acceleration by self-controlled
      ionization injection.
AB  - We report on overall enhancement of a single-stage laser wakefield acceleration
      (LWFA) using the ionization injection in a mixture of 0.3% nitrogen gas in 99.7%
      helium gas. Upon the interaction of 30-TW, 30-fs laser pulses with a gas jet of
      the above gas mixture, >300 MeV electron beams were generated at a helium plasma
      densities of 3.3-8.5 * 10(18) cm(-3). Compared with the uncontrolled electron
      self-injection in pure helium gas jet, the ionization injection process due to
      the presence of ultra-low nitrogen concentrations appears to be self-controlled;
      it has led to the generation of electron beams with higher energies, higher
      charge, lower density threshold for trapping, and a narrower energy spread
      without dark current (low energy electrons) or multiple bunches. It is foreseen
      that further optimization of such a scheme is expected to bring the electron beam
      energy-spread down to 1%, making them suitable for driving ultra-compact free
      electron lasers.

PMID- 25606891
TI  - Function fitting the symmetric radiation pattern of a LED with attached secondary
      optic.
AB  - The analytical model [Moreno and Sun, Opt. Express 16, 1808-1819 (2008)] is
      applied to LED with attached secondary optics. It is shown that a slightly
      modified model using only three cosine power functions can be used for the cases
      with symmetric radiation pattern and that good fitting on realistic examples can
      be achieved with several standard optimization algorithms including local search
      heuristics and genetic algorithm. 

PMID- 25606892
TI  - Digital holography based on multiwavelength spatial-bandwidth-extended capturing
      technique using a reference arm (Multi-SPECTRA).
AB  - Single-shot digital holography based on multiwavelength spatial-bandwidth
      extended capturing-technique using a reference arm (Multi-SPECTRA) is proposed.
      Both amplitude and quantitative phase distributions of waves containing multiple
      wavelengths are simultaneously recorded with a single reference arm in a single
      monochromatic image. Then, multiple wavelength information is separately
      extracted in the spatial frequency domain. The crosstalk between the object waves
      with different wavelengths is avoided and the number of wavelengths recorded with
      both a single-shot exposure and no crosstalk can be increased, by a large spatial
      carrier that causes the aliasing, and/or by use of a grating. The validity of
      Multi-SPECTRA is quantitatively, numerically, and experimentally confirmed. 

PMID- 25606893
TI  - Attenuated total reflectance spectroscopy with chirped-pulse upconversion.
AB  - Chirped-pulse upconversion technique has been applied to attenuated total
      reflectance (ATR) infrared spectroscopy. An extremely broadband infrared pulse
      was sent to an ATR diamond prism and the reflected pulse was converted to the
      visible by using four-wave mixing in krypton gas. Absorption spectra of liquids
      in the range from 200 to 5500 cm(-1) were measured with a visible spectrometer on
      a single-shot basis. The system was applied to observe the dynamics of exchanging
      process of two solvents, water and acetone, which give clear vibrational spectral
      contrast. We observed that the exchange was finished within ~ 10 ms.

PMID- 25606894
TI  - Reflection-type integral imaging system using a diffuser holographic optical
      element.
AB  - A reflection-type integral imaging (InIm) system using a diffuser holographic
      optical element (DHOE) is proposed for improving the fill factor of displayed
      three-dimensional images. The DHOE performs an optical function similar to that
      for a conventional diffuser only for Bragg matched light, while Bragg mismatched
      light passes through the DHOE. Elemental images projected under Bragg matching
      condition are scattered by the DHOE. Meanwhile, light reflected by a concave
      mirror-array becomes Bragg mismatched light, and is integrated into three
      dimensional images without the fill factor problem. The optical characteristics
      of the DHOE are examined by measuring diffraction efficiencies, and the
      feasibility of the fill-factor-improved InIm is verified by a concave mirror
      array and DHOE. 

PMID- 25606895
TI  - Dual-functional sensor based on switchable plasmonic structure of VO2 nano
      crystal films and Ag nanoparticles.
AB  - Utilizing the insulator-metal phase transition of vanadium dioxide (VO2) crystal
      films, we develop a dual-functional sensor based on the coupling between VO2 nano
      crystal films and Ag nanoparticles, which can probe fluorescence or Raman signals
      on the same substrate and it is switchable by changing temperature. At room
      temperature, the VO2 crystal films is insulator phase and the fluorescence
      signals of probe molecules (R6G) is detectable (Raman is in "off"). At high
      temperature (such as 85  degrees C), the VO2 crystal films become metallic phase.
      Ag nanoparticles interact with the metal phase of VO2 crystal films to produce
      stronger localized electric field. The stronger electric field can excite the
      Raman signals of probe molecules (R6G) and the coupled structure can also emit
      the Raman signals out efficiently (Raman is in "on"). The switchable probe of
      fluorescence and Raman signals would have potential applications in active
      photoelectric components, such as intelligent switch and multifunctional active
      sensor etc.

PMID- 25606896
TI  - Influence of the device parameters in ICRBD on SSB-OOFDM signal with reduced
      guard band.
AB  - The paper has theoretically evaluated a signal-signal beat interference (SSBI)
      cancellation receiver with the balanced detection (ICRBD) for single sideband
      optical orthogonal frequency division multiplexing (SSB-OOFDM) signal, which has
      an improved spectral efficiency (SE) by reducing the guard band (GB) between the
      OOFDM signal and the optical carrier. The influences of the parameters of the
      interleaver (IL), the optical coupler (OC), and the balanced photodiodes (BPD) as
      well as the connecting optical/electrical paths in the ICRBD on the received OFDM
      signal performance are studied in detail. The theoretical results show that the
      received OFDM signal and noise power are dependent on the parameters of the
      devices and their deviation away from the ideal value degrades the performance
      greatly. Based on the simulation system, the 40 Gb/s 16QAM SSB-OOFDM signal with
      5 GHz GB is converted to the OFDM signal by the ICRBD with the suppressed SSBI.
      It is observed that (1) the received OFDM signal is insensitive to the deviation
      of the coupling coefficient of the 3 dB OC; (2) the received signal suffers
      little degradation from the filter outline of the IL if an IL with the bandwidth
      over 13 GHz and 6- or higher-order Gaussian filter is used; (3) the polarization
      deviation and phase shift between the OOFDM signal and the optical carrier caused
      by the optical paths between IL and OC have smaller influence on the EVM of the
      received signal; and (4) although the ICRBD is immune to the polarization
      deviation of the two recombined SSB-OOFDM signals, the relative time delay
      between the two optical/electrical paths from the OC to the BPD degrades the
      received signal seriously. By tuning the time delay in optical or electrical
      domain to reduce the total relative time delay within 10 ps, the EVM maintains
      below 20%. The simulation results agree well with the theoretical analysis and
      catch an insight on the mechanism of the ICRBD.

PMID- 25606897
TI  - Temperature retrieval from Rayleigh-Brillouin scattering profiles measured in
      air.
AB  - In order to investigate the performance of two different algorithms for
      retrieving temperature from Rayleigh-Brillouin (RB) line shapes, RB scattering
      measurements have been performed in air at a wavelength of 403 nm, for a
      temperature range from 257 K to 330 K, and atmospherically relevant pressures
      from 871 hPa to 1013 hPa. One algorithm, based on the Tenti S6 line shape model,
      shows very good accordance with the reference temperature. In particular, the
      absolute difference is always less than 2 K. A linear correlation yields a slope
      of 1.01 +/- 0.02 and thus clearly demonstrates the reliability of the retrieval
      procedure. The second algorithm, based on an analytical line shape model, shows
      larger discrepancies of up to 9.9 K and is thus not useful at its present stage.
      The possible reasons for these discrepancies and improvements of the analytical
      model are discussed. The obtained outcomes are additionally verified with
      previously performed RB measurements in air, at 366 nm, temperatures from 255 K
      to 338 K and pressures from 643 hPa to 826 hPa [Appl. Opt. 52, 4640 (2013)]. The
      presented results are of relevance for future lidar studies that might utilize RB
      scattering for retrieving atmospheric temperature profiles with high accuracy. 

PMID- 25606898
TI  - Chromatic control in coextruded layered polymer microlenses.
AB  - We describe the formation, characterization and theoretical understanding of
      microlenses comprised of alternating polystyrene and polymethylmethacrylate
      layers produced by multilayer coextrusion. These lenses are fabricated by
      photolithography, using a grayscale mask followed by plasma etching, so that the
      refractive index alternation of the bilayer stack appears across the radius of
      the microlens. The alternating quarter-wave thick layers form a one-dimensional
      photonic crystal whose dispersion augments the material dispersion, allowing one
      to sculpt the chromatic dispersion of the lens by adjusting the layered
      structure. Using Huygen's principle, we model our experimental measurements of
      the focal length of these lenses across the reflection band of the multilayer
      polymer film from which the microlens is fashioned. For a 56 MUm diameter
      multilayered lens of focal length 300 MUm, we measured a ~ 25% variation in the
      focal length across a shallow, 50 nm-wide reflection band. 

PMID- 25606899
TI  - Discrete solitons and vortices on two-dimensional lattices of PT-symmetric
      couplers.
AB  - We introduce a 2D network built of PT-symmetric dimers with on-site cubic
      nonlinearity, the gain and loss elements of the dimers being linked by parallel
      square-shaped lattices. The system may be realized as a set of PT-symmetric dual
      core waveguides embedded into a photonic crystal. The system supports PT
      symmetric and antisymmetric fundamental solitons (FSs) and on-site-centered
      solitary vortices (OnVs). Stability of these discrete solitons is the central
      topic of the consideration. Their stability regions in the underlying parameter
      space are identified through the computation of stability eigenvalues, and
      verified by direct simulations. Symmetric FSs represent the system's ground
      state, being stable at lowest values of the power, while anti-symmetric FSs and
      OnVs are stable at higher powers. Symmetric OnVs, which are also stable at lower
      powers, are remarkably robust modes: on the contrary to other PT-symmetric
      states, unstable OnVs do not blow up, but spontaneously rebuild themselves into
      stable FSs.

PMID- 25606900
TI  - Fano resonances in the nonlinear optical response of coupled plasmonic
      nanostructures.
AB  - The coupling between metallic nanostructures is a common and easy way to control
      the optical properties of plasmonic systems. Even though the coupling between
      plasmonic oscillators has been widely studied in the linear regime, its influence
      on the nonlinear optical response of metallic nanostructures has been sparsely
      considered. Using a surface integral equation method, we investigate the second
      order nonlinear optical response of plasmonic metamolecules supporting Fano
      resonances revealing that the typical lineshape of Fano resonances is also
      clearly observable in the nonlinear regime. The physical mechanisms leading to
      nonlinear Fano resonances are revealed by the coupled oscillator model and the
      symmetry subgroup decomposition. It is found that the origin of the nonlinear
      scattered wave, i. e. the active plasmonic oscillator, can be selectively chosen.
      Furthermore, interferences between nonlinear emissions are clearly observed in
      specific configurations. The results presented in this article pave the way for
      the design of efficient nonlinear plasmonic metamolecules with controlled
      nonlinear radiation. 

PMID- 25606901
TI  - Dark pulse generation in fiber lasers incorporating carbon nanotubes.
AB  - We demonstrate the generation of dark pulses from carbon nanotube (CNT)
      incorporated erbium-doped fiber ring lasers with net anomalous dispersion. A side
      polished fiber coated with CNT layer by optically-driven deposition method is
      embedded into the laser in order to enhance the birefringence and nonlinearity of
      the laser cavity. The dual-wavelength domain-wall dark pulses are obtained from
      the developed CNT-incorporated fiber laser at a relatively low pump threshold of
      50.6 mW. Dark pulses repeated at the fifth-order harmonic of the fundamental
      cavity frequency are observed by adjusting the intra-cavity polarization state. 

PMID- 25606902
TI  - Low-threshold mode instability in Yb3+-doped few-mode fiber amplifiers.
AB  - Spatio-temporal instability of the fundamental mode in Yb(3+)-doped few-mode PM
      fiber amplifiers with a core diameter of 8.5 MUm was registered at 2-30 Watts
      pump power. Both experimental and theoretical analysis revealed the nonlinear
      power transformation of the LP(01) fundamental mode into high-order modes.
      Numerical simulation revealed self-consistent growth of the higher-order mode and
      traveling electronic index grating accompanying the population grating induced by
      the mode interference field (due to different polarizability of the excited and
      unexcited Yb(3+) ions). Experimental results and numerical calculations showed
      the increase of the instability threshold along with an increase of the signal
      frequency bandwidth.

PMID- 25606903
TI  - Fiber-integrated 780 nm source for visible parametric generation.
AB  - We report the development of a fully fiber-integrated pulsed master oscillator
      power fibre amplifier (MOPFA) source at 780 nm, producing 3.5 W of average power
      with 410 ps pulses at a repetition rate of 50 MHz. The source consists of an
      intensity modulated 1560 nm laser diode amplified in an erbium fiber amplifier
      chain, followed by a fiber coupled periodically poled lithium niobate crystal
      module for frequency doubling. The source is then used for generating visible
      light through four-wave mixing in a length of highly nonlinear photonic crystal
      fiber: 105 mW at 668 nm and 95 mW at 662 nm are obtained, with pump to anti
      Stokes conversion slope efficiencies exceeding 6% in both cases. 

PMID- 25606904
TI  - Multi-stage perturbation theory for compensating intra-channel nonlinear
      impairments in fiber-optic links.
AB  - A recursive perturbation theory to model the fiber-optic system is developed.
      Using this perturbation theory, a multi-stage compensation technique to mitigate
      the intra-channel nonlinear impairments is investigated. The technique is
      validated by numerical simulations of a single-polarization single-channel fiber
      optic system operating at 28 Gbaud, 32-quadrature amplitude modulation (32-QAM),
      and 40 * 80 km transmission distance. It is found that, with 2 samples per
      symbol, the multi-stage scheme with eight compensation stages increases the Q
      factor as compared with linear compensation by 4.5 dB; as compared with single
      stage compensation, the computational complexity is reduced by a factor of 1.3
      and the required memory for storing perturbation coefficients is decreased by a
      factor of 13. 

PMID- 25606905
TI  - Optical sorting of nonspherical and living microobjects in moving interference
      structures.
AB  - Contactless, sterile and nondestructive separation of microobjects or living
      cells is demanded in many areas of biology and analytical chemistry, as well as
      in physics or engineering. Here we demonstrate advanced sorting methods based on
      the optical forces exerted by travelling interference fringes with tunable
      periodicity controlled by a spatial light modulator. Besides the sorting of
      spherical particles we also demonstrate separation of algal cells of different
      sizes and particles of different shapes. The three presented methods offer
      simultaneous sorting of more objects in static suspension placed in a Petri dish
      or on a microscope slide. 

PMID- 25606906
TI  - Size dependence of band structures in a two-dimensional plasmonic crystal with a
      square lattice.
AB  - A scanning transmission electron microscope (STEM) -cathodoluminescence (CL)
      technique is used to investigate the size dependence of the band structures in
      two-dimensional plasmonic crystals with a square lattice (SQ-PlCs) composed of
      cylindrical pillars and holes. The experimentally determined and calculated
      dependences of the band edge energies of the three SPP modes at the Gamma point
      on the diameter of the cylindrical structure agree well. The photon maps reveal
      the field strength distributions of the standing SPP waves of the three
      eigenmodes. Additionally, a mechanism is proposed to explain the dependence of
      the contrast on the detected light polarization. 

PMID- 25606907
TI  - Non-collinear high-order harmonic generation by three interfering laser beams.
AB  - High order harmonic generation (HHG) has shown its impact on several applications
      in Attosecond Science and Atomic and Molecular Physics. Owing to the complexity
      of the experimental setup for the generation and characterization of harmonics,
      as well as to the large computational costs of numerical modelling, HHG is
      generally performed and modelled in collinear geometry. Recently, several
      experiments have been performed exploiting non-collinear geometry, such as HHG in
      a grating of excited molecules created by crossing beams. In such studies,
      harmonics were observed at propagation directions different from those of the
      driving pulses; moreover the scattered harmonics were angularly dispersed.In this
      work we report on a new regime of HHG driven by multiple beams, where the
      harmonics are generated by three synchronized, intense laser pulses organized in
      a non-planar geometry. Although the configuration we explore is well within the
      strong-field regime, the scattered harmonics we observe are not angularly
      dispersed. 

PMID- 25606908
TI  - Continuous measurement of optical surfaces using a line-scan interferometer with
      sinusoidal path length modulation.
AB  - We present a fast approach to the continuous measurement of rotational symmetric
      optical surfaces. This approach is based on a line scanning interferometer with
      sinusoidal modulation of the optical path length. The specimen is positioned with
      respect to the sensor and both are moved during measurement by use of a five axes
      system comprising a high precision rotational table. The calibration of both the
      line sensor as well as the scanning and positioning system is discussed. As proof
      of principle of the measurement and stitching concept results of a scan of a
      rotational symmetric sinusoidal structure and a spherical lens with a moderate
      slope are shown. 

PMID- 25606909
TI  - Highly transparent privacy filter film with image distortion.
AB  - We present a novel privacy filter film with transparent micro-cuboid arrays. The
      privacy filter film, which does not include any opaque materials, rarely affects
      the normal transparency, whereas it obscures personal information by distorting
      paths of oblique light rays. The effects of the cuboid size and a gap between the
      privacy filter and a display are analyzed using a ray-tracing program. The
      analysis is consistent with the experimental results carried out using the poly
      dimethylsiloxane (PDMS) micro-cuboid (100 MUm * 100 MUm * 200 MUm) arrays, which
      are fabricated by lithography and transfer molding. 

PMID- 25606910
TI  - Three-dimensional super-resolution structured illumination microscopy with
      maximum a posteriori probability image estimation.
AB  - We introduce and demonstrate a new high performance image reconstruction method
      for super-resolution structured illumination microscopy based on maximum a
      posteriori probability estimation (MAP-SIM). Imaging performance is demonstrated
      on a variety of fluorescent samples of different thickness, labeling density and
      noise levels. The method provides good suppression of out of focus light,
      improves spatial resolution, and allows reconstruction of both 2D and 3D images
      of cells even in the case of weak signals. The method can be used to process both
      optical sectioning and super-resolution structured illumination microscopy data
      to create high quality super-resolution images. 

PMID- 25606911
TI  - Compact 2 * 2 polarization-diversity Si-wire switch.
AB  - A polarization-independent 2 * 2 switch based on silicon-wire waveguides has been
      realized with a compact size of 600 * 500 MUm2. Polarization-independent
      operation was achieved with a polarization-diversity technique which implements
      polarization splitters, TE-TM intersections, and Mach-Zehnder switches. The
      extinction ratios of the 2 * 2 switch for TE, TM, and a mixed polarization at a
      wavelength of 1550 nm were measured to be larger than 30 dB, 25 dB, and 30 dB,
      respectively. The measured switching powers for the TE and TM polarizations were
      25 and 55 mW, respectively. The measured polarization-dependent loss was lower
      than 1 dB. The differential group delay (DGD) between the TE and TM modes was
      also evaluated using the Mueller matrix method, which was in good agreement with
      the values estimated from the path lengths for each mode. A path-length
      compensated switch was fabricated, whose DGDs for all paths were indeed as small
      as ~2 ps, mainly from the access waveguides. The switch could provide an
      important route to develop ultra-compact polarization-independent integrated
      circuits based on silicon-wire waveguides.

PMID- 25606912
TI  - On the impact of polarization-dependent gain/loss for optical multicast sessions.
AB  - This work focuses on the design and engineering of metropolitan area optical
      networks for multicast session provisioning. Specifically, the impact of
      polarization-dependent gain/loss of optical components in coordination with other
      physical layer impairments is investigated for the first time for several optical
      multicast algorithms and switch designs. Performance results indicate that the
      conventional probabilistic handling of PDG/PDL is not practical in this case,
      requiring a more refined and computationally efficient interaction between
      physical and control layers. 

PMID- 25606913
TI  - Model based scattering correction in time-of-flight cameras.
AB  - In-camera light scattering is a systematic error of Time-of-Flight depth cameras
      that significantly reduces the accuracy of the systems. A completely new model is
      presented, based on raw data calibration and only one additional intrinsic camera
      parameter. It is shown that the approach effectively removes the errors of in
      camera light scattering. 

PMID- 25606914
TI  - Thickness-dependent crystallization on thermal anneal for titania/silica nm-layer
      composites deposited by ion beam sputter method.
AB  - Crystallization following thermal annealing of thin film stacks consisting of
      alternating nm-thick titania/silica layers was investigated. Several prototypes
      were designed, featuring a different number of titania/silica layer pairs, and
      different thicknesses (in the range from 4 to 40 nm, for the titania layers), but
      the same nominal refractive index (2.09) and optical thickness (a quarter of
      wavelength at 1064 nm). The prototypes were deposited by ion beam sputtering on
      silicon substrates. All prototypes were found to be amorphous as-deposited.
      Thermal annealing in air at progressive temperatures was subsequently performed.
      It was found that the titania layers eventually crystallized forming the anatase
      phase, while the silica layers remained always amorphous. However, progressively
      thinner layers exhibited progressively higher threshold temperatures for
      crystallization onset. Accordingly it can be expected that composites with
      thinner layers will be able to sustain higher annealing temperatures without
      crystallizing, and likely yielding better optical and mechanical properties for
      advanced coatings application. These results open the way to the use of materials
      like titania and hafnia, that crystallize easily under thermal anneal, but ARE
      otherwise promising candidate materials for HR coatings necessary for cryogenic
      3rd generation laser interferometric gravitational wave detectors. 

PMID- 25606915
TI  - Femtosecond direct-written integrated mode couplers.
AB  - We report the design and fabrication of three-dimensional integrated mode
      couplers operating in the C-band. These mode-selective couplers were inscribed
      into a boro-aluminosilicate photonic chip using the femtosecond laser direct
      write technique. Horizontally and vertically written two-core couplers are shown
      to allow for the multiplexing of the LP11a and LP11b spatial modes of an optical
      fiber, respectively, with excellent mode extinction ratios (25-37 + dB) and low
      loss (~1 dB) between 1500 and 1580 nm. Furthermore, optimized fabrication
      parameters enable coupling ratios close to 100%. When written in sequence, the
      couplers allow for the multiplexing of all LP01, LP11a and LP11b modes. This is
      also shown to be possible using a single 3-dimensional three-core coupler. These
      integrated mode couplers have considerable potential to be used in mode-division
      multiplexing for increasing optical fiber capacity. The three-dimensional
      capability of the femtosecond direct-write technique provides the versatility to
      write linear cascades of such two- and three-core couplers into a single compact
      glass chip, with arbitrary routing of waveguides to ensure a small footprint.
      This technology could be used for high-performance, compact and cost-effective
      multiplexing of large numbers of modes of an optical fiber.

PMID- 25606916
TI  - Controllable Akhmediev breather and Kuznetsov-Ma soliton trains in PT-symmetric
      coupled waveguides.
AB  - The PT-symmetric and PT-antisymmetric Akhmediev breather (AB) and Kuznetsov-Ma
      (KM) soliton train solutions of a (2+1)-dimensional variable-coefficient coupled
      nonlinear Schrodinger equation in PT-symmetric coupled waveguides with gain and
      loss are derived via the Darboux transformation method. From these analytical
      solutions, we investigate the controllable behaviors of AB and KM soliton trains
      in a diffraction decreasing system with exponential profile. By adjusting the
      relation between the maximum Zm of effective propagation distance and the peak
      locations Zi of AB and KM soliton trains, we can control the restraint,
      maintenance and postpone excitations of AB and KM soliton trains.

PMID- 25606917
TI  - Optical network scaling: roles of spectral and spatial aggregation.
AB  - As the bit rates of routed data streams exceed the throughput of single
      wavelength-division multiplexing channels, spectral and spatial traffic
      aggregation become essential for optical network scaling. These aggregation
      techniques reduce network routing complexity by increasing spectral efficiency to
      decrease the number of fibers, and by increasing switching granularity to
      decrease the number of switching components. Spectral aggregation yields a modest
      decrease in the number of fibers but a substantial decrease in the number of
      switching components. Spatial aggregation yields a substantial decrease in both
      the number of fibers and the number of switching components. To quantify routing
      complexity reduction, we analyze the number of multi-cast and wavelength
      selective switches required in a colorless, directionless and contentionless
      reconfigurable optical add-drop multiplexer architecture. Traffic aggregation has
      two potential drawbacks: reduced routing power and increased switching component
      size. 

PMID- 25606918
TI  - Optical birefringence of Zn nanoparticles embedded in silica induced by swift
      heavy-ion irradiation.
AB  - Zn nanoparticles (NPs) embedded in a silica matrix subjected to irradiation with
      swift heavy ions of 200 MeV Xe14+ have been found to undergo shape elongation
      from spheres to prolate-spheroids while maintaining the major axes of the NPs in
      parallel alignment. The directionally-aligned Zn spheroids enable acquisition of
      optical properties, such as linear dichroism and birefringence. In this paper,
      the birefringence of the Zn spheroids was evaluated by the crossed-Nicols (XN)
      transmittance, where a sample was inserted between a pair of optical polarizers
      that were set in an orthogonal configuration. Linearly-polarized light aligned by
      the first polarizer was transformed to an elliptic polarization by the
      birefringence of the Zn spheroids. The existence of the birefringence was
      confirmed by the non-zero transmittance of the second polarizer in the orthogonal
      configuration. The sample irradiated with a fluence of 5.0 * 1013 ions/cm2
      exhibited a maximum XN transmittance of 2.1% at a photon energy of ~4 eV. The XN
      transmission was observed down to a fluence of 1.0 * 1012 ions/cm2, but reduced
      below the detection limit at a fluence of 1.0 * 1011 ions/cm2. The possible
      application of the elongated Zn NPs as a polarizer with nanometric thickness
      working in the near- and mid-ultraviolet region is discussed.

PMID- 25606919
TI  - Measurement of the refractive index by using a rectangular cell with a fs-laser
      engraved diffraction grating inner wall.
AB  - A very simple method to obtain the refractive index of liquids by using a
      rectangular glass cell and a diffraction grating engraved by fs laser ablation on
      the inner face of one of the walls of the cell is presented. When a laser beam
      impinges normally on the diffraction grating, the diffraction orders are deviated
      when they pass through the cell filled with the liquid to be measured. By
      measuring the deviation of the diffraction orders, we can determine the
      refractive index of the liquid. 

PMID- 25606920
TI  - High-power, single-frequency, continuous-wave optical parametric oscillator
      employing a variable reflectivity volume Bragg grating.
AB  - A continuous-wave singly-resonant optical parametric oscillator (SRO) with an
      optimum extraction efficiency, that can be adjusted independent of the pump
      power, is demonstrated. The scheme employs a variable-reflectivity volume Bragg
      grating (VBG) as the output coupler of a ring cavity, omitting any additional
      intra-cavity elements. In this configuration, we obtained a 75%-efficient SRO
      with a combined signal (19 W @ 1.55 um) and idler (11 W @ 3.4 um) output power of
      30 W. 

PMID- 25606921
TI  - PN-type carrier-induced filter with modulatable extinction ratio.
AB  - We demonstrate the first PN-type carrier-induced silicon waveguide Bragg grating
      filter on a SOI wafer. The optical extinction ratio of this kind of filter can be
      efficiently modulated under both reverse and forward biases. The carrier-induced
      Bragg grating based on a PN junction is fabricated on the silicon waveguide using
      litho compensation technology. The measured optical bandwidth and the extinction
      ratio of the filter are 0.45 nm and 19 dB, respectively. The optical extinction
      ratio modulation under the reverse bias is more than 11.5 dB and it is more than
      10 dB under the forward bias. Only 1-dB optical transmission loss is realized in
      this Bragg grating under a reverse bias. The shifting rates of the central
      wavelength under forward and reverse biases are ~-1.25 nm/V and 0.01 nm/V,
      respectively. The 3-dB modulation bandwidth of this filter is 5.1 GHz at a bias
      of -10 V. 

PMID- 25606922
TI  - 1.61 MUm high-order passive harmonic mode locking in a fiber laser based on
      graphene saturable absorber.
AB  - We demonstrate a passive mode-locked Er:Yb doped double-clad ring fiber laser
      based on graphene saturable absorber. By adjusting the polarization controller
      and minimizing the cavity loss, the laser can operate at hundreds of harmonics of
      the fundamental repetition frequency of the resonator with the central wavelength
      of 1.61 MUm. Up to 683rd harmonic (which corresponds to 5.882 GHz) of the
      fundamental repetition frequency was achieved. 

PMID- 25606923
TI  - Low-power silicon-organic hybrid (SOH) modulators for advanced modulation
      formats.
AB  - We demonstrate silicon-organic hybrid (SOH) electro-optic modulators that enable
      quadrature phase-shift keying (QPSK) and 16-state quadrature amplitude modulation
      (16QAM) with high signal quality and record-low energy consumption. SOH
      integration combines highly efficient electro-optic organic materials with
      conventional silicon-on-insulator (SOI) slot waveguides, and allows to overcome
      the intrinsic limitations of silicon as an optical integration platform. We
      demonstrate QPSK and 16QAM signaling at symbol rates of 28 GBd with peak-to-peak
      drive voltages of 0.6 V(pp). For the 16QAM experiment at 112 Gbit/s, we measure a
      bit-error ratio of 5.1 * 10-5 and a record-low energy consumption of only 19
      fJ/bit.

PMID- 25606924
TI  - Generalized method for retrieving effective parameters of anisotropic
      metamaterials.
AB  - Electromagnetic or acoustic metamaterials can be described in terms of equivalent
      effective, in general anisotropic, media and several techniques exist to
      determine the effective permeability and permittivity (or effective mass density
      and bulk modulus in the context of acoustics). Among these techniques, retrieval
      methods use the measured reflection and transmission coefficients (or scattering
      coefficients) for waves incident on a metamaterial slab containing few unit
      cells. Until now, anisotropic effective slabs have been considered in the
      literature but they are limited to the case where one of the axes of anisotropy
      is aligned with the slab interface. We propose an extension to arbitrary
      orientations of the principal axes of anisotropy and oblique incidence. The
      retrieval method is illustrated in the electromagnetic case for layered media,
      and in the acoustic case for array of tilted elliptical particles. 

PMID- 25606925
TI  - Silicon waveguide filter based on cladding modulated anti-symmetric long-period
      grating.
AB  - In this paper, we demonstrate an optical filter using cladding modulated anti
      symmetric long-period grating in a two-mode silicon waveguide. The filter
      consists of a two-mode waveguide connected with an input and output single-mode
      waveguide through two linear tapers. The anti-symmetric grating is formed by
      placing two periodic arrays of silicon squares offset by half of a grating pitch
      along the two-mode waveguide. Light coupling occurs between two co-propagating
      modes at the coupling wavelength through the grating and results in a rejection
      band at the output. The grating pitch, coupling coefficient, transmission
      spectrum and 3-dB bandwidth of the grating are investigated with the coupled-mode
      theory. By using a cladding modulated grating, the grating coupling strength can
      be controlled over a wide range by the two-mode waveguide width or separation
      distance between the grating and waveguide. Band-rejection filters are
      experimentally demonstrated in 1-MUm, 0.8-MUm and 0.7-MUm wide two-mode silicon
      waveguides and rejection bands with different bandwidths and maximal attenuation
      contrasts larger than 15 dB (~97% coupling efficiency) have been achieved. 

PMID- 25606926
TI  - Backward Lasing of Air plasma pumped by Circularly polarized femtosecond pulses
      for the saKe of remote sensing (BLACK).
AB  - Recently, S. Mitryukovskiy et al. presented experimental evidence showing that
      backward Amplified Spontaneous Emission (ASE) at 337 nm can be obtained from
      plasma filaments in nitrogen gas pumped by circularly polarized 800 nm
      femtosecond pulses (Opt. Express, 22, 12750 (2014)). Here, we report that a seed
      pulse injected in the backward direction can be amplified by ~200 times inside
      this plasma amplifier. The amplified 337 nm radiation can be either linearly or
      circularly polarized, dictated by the seeding pulse, which is distinct from the
      non-polarized nature of the ASE. We performed comprehensive measurements of the
      spatial profile, optical gain dynamics, and seed pulse energy dependence of this
      amplification process. These measurements allow us to deduce the pulse duration
      of the ASE and the amplified 337 nm radiation as well as the corresponding laser
      intensity inside the plasma amplifier. It indicates that the amplification is
      largely in the unsaturated regime and that further improvement of laser energy is
      possible. Moreover, we observed optical gain in plasma created in ambient air.
      This represents an important step towards future applications exploiting backward
      lasing for remote atmospheric sensing. 

PMID- 25606927
TI  - High-efficiency Si optical modulator using Cu travelling-wave electrode.
AB  - We demonstrate a high-efficiency and CMOS-compatible silicon Mach-Zehnder
      Interferometer (MZI) optical modulator with Cu traveling-wave electrode and
      doping compensation. The measured electro-optic bandwidth at Vbias = -5 V is
      above 30 GHz when it is operated at 1550 nm. At a data rate of 50 Gbps, the
      dynamic extinction ratio is more than 7 dB. The phase shifter is composed of a 3
      mm-long reverse-biased PN junction with modulation efficiency (Vpi.Lpi) of ~18.5
      V.mm. Such a Cu-photonics technology provides an attractive potentiality for
      integration development of silicon photonics and CMOS circuits on SOI wafer in
      the future.

PMID- 25606928
TI  - Optical depth localization of nitrogen-vacancy centers in diamond with nanometer
      accuracy.
AB  - Precise positioning of nitrogen-vacancy (NV) centers is crucial for their
      application in sensing and quantum information. Here we present a new purely
      optical technique enabling determination of the NV position with nanometer
      resolution. We use a confocal microscope to determine the position of individual
      emitters along the optical axis. Using two separate detection channels, it is
      possible to simultaneously measure reflected light from the diamond surface and
      fluorescent light from the NV center and statistically evaluate both signals. An
      accuracy of 2.6 nm for shallow NV centers was achieved and is consistent with
      other techniques for depth determination. 

PMID- 25606929
TI  - Fluorescent porous silicon biological probes with high quantum efficiency and
      stability.
AB  - We demonstrate porous silicon biological probes as a stable and non-toxic
      alternative to organic dyes or cadmium-containing quantum dots for imaging and
      sensing applications. The fluorescent silicon quantum dots which are embedded on
      the porous silicon surface are passivated with carboxyl-terminated ligands
      through stable Si-C covalent bonds. The porous silicon bio-probes have shown
      photoluminescence quantum yield around 50% under near-UV excitation, with high
      photochemical and thermal stability. The bio-probes can be efficiently conjugated
      with antibodies, which is confirmed by a standard enzyme-linked immunosorbent
      assay (ELISA) method. 

PMID- 25606930
TI  - High-precision x-ray FEL pulse arrival time measurements at SACLA by a THz streak
      camera with Xe clusters.
AB  - The accurate measurement of the arrival time of a hard X-ray free electron laser
      (FEL) pulse with respect to a laser is of utmost importance for pump-probe
      experiments proposed or carried out at FEL facilities around the world. This
      manuscript presents the latest device to meet this challenge, a THz streak camera
      using Xe gas clusters, capable of pulse arrival time measurements with an
      estimated accuracy of several femtoseconds. An experiment performed at SACLA
      demonstrates the performance of the device at photon energies between 5 and 10
      keV with variable photon beam parameters. 

PMID- 25606931
TI  - Mapping the transverse coherence of the self amplified spontaneous emission of a
      free-electron laser with the heterodyne speckle method.
AB  - The two-dimensional single shot transverse coherence of the Self-Amplified
      Spontaneous Emission of the SPARC_LAB Free-Electron Laser was measured through
      the statistical analysis of a speckle field produced by heterodyning the
      radiation beam with a huge number of reference waves, scattered by a suspension
      of particles. In this paper we report the measurements and the evaluation of the
      transverse coherence along the SPARC_LAB undulator modules. The measure method
      was demonstrated to be precise and robust, it does not require any a priori
      assumptions and can be implemented over a wide range of wavelengths, from the
      optical radiation to the x-rays. 

PMID- 25606932
TI  - Reflectivity of transient Bragg reflection gratings in fiber laser with laser
      wavelength self-sweeping.
AB  - We present a method for the estimation of the reflection spectra of transient
      gratings in rare-earth doped fiber lasers having a self-sweeping of laser
      wavelength. We show that high reflectivities of several tens of percent can be
      achieved. An example of this is demonstrated through the use of an experimental
      Yb-doped Fabry-Perot fiber laser. The gratings' spectra are highly asymmetric due
      to the apodization of the refractive index modulation. The importance of the self
      sweeping regime for triggering self-Q-switched laser instabilities is discussed. 

PMID- 25606933
TI  - An ab-initio coupled mode theory for near field radiative thermal transfer.
AB  - We investigate the thermal transfer between finite-thickness planar slabs which
      support surface phonon polariton modes (SPhPs). The thickness-dependent
      dispersion of SPhPs in such layered materials provides a unique opportunity to
      manipulate and enhance the near field thermal transfer. The key accomplishment of
      this paper is the development of an ab-initio coupled mode theory that accurately
      describes all of its thermal transfer properties. We illustrate how the coupled
      mode parameters can be obtained in a direct fashion from the dispersion relation
      of the relevant modes of the system. This is illustrated for the specific case of
      a semi-infinite SiC substrate placed in close proximity to a thin slab of SiC.
      This is a system that exhibits rich physics in terms of its thermal transfer
      properties, despite the seemingly simple geometry. This includes a universal
      scaling behavior of the thermal conductance with the slab thickness and spacing.
      The work highlights and further increases the value of coupled mode theories in
      rapidly calculating and intuitively understanding near-field transfer. 

PMID- 25606934
TI  - Picosecond optical parametric generator and amplifier for large temperature-jump.
AB  - An optical parametric generator and amplifier producing 15 ps pulses at
      wavelengths tunable around 2 MUm, with energies up to 15 mJ/pulse, has been
      realized and characterized. The output wavelength is chosen to match a
      vibrational combination band of water. By measuring the induced birefringence
      changes we prove that a single pulse is able to completely melt samples of ice in
      the 10-6 cm3 volume range, both at room pressure (263 K) and at high pressure
      (298 K, 1 GPa) in a sapphire anvil cell. This source opens the possibility of
      studying melting and freezing processes by spectroscopic probes in water or water
      solutions in a wide range of conditions as found in natural environments.

PMID- 25606935
TI  - On the performance of multichannel digital backpropagation in high-capacity long
      haul optical transmission.
AB  - The performance of digital backpropagation (DBP) equalization when applied over
      multiple channels to compensate for the nonlinear impairments in optical fiber
      transmission systems is investigated. The impact of a suboptimal multichannel DBP
      operation is evaluated, where implementation complexity is reduced by varying
      parameters such as the number of nonlinear steps per span and sampling rate.
      Results have been obtained for a reference system consisting of a 5*32 Gbaud PDM
      16QAM superchannel with 33 GHz subchannel spacing and Nyquist pulse shaping under
      long-haul transmission. The reduction in the effectiveness of the algorithm is
      evaluated and compared with the ideal gain expected from the cancellation of the
      nonlinear signal distortion. The detrimental effects of polarization mode
      dispersion (PMD) with varying DBP bandwidth are also studied. Key parameters
      which ensure the effectiveness of multichannel DBP are identified. 

PMID- 25606936
TI  - Object reconstitution using pseudo-inverse for ghost imaging.
AB  - We propose a novel method for object reconstruction of ghost imaging based on
      Pseudo-Inverse, where the original objects are reconstructed by computing the
      pseudo-inverse of the matrix constituted by the row vectors of each speckle
      field. We conduct reconstructions for binary images and gray-scale images. With
      equal number of measurements, our method presents a satisfying performance on
      enhancing Peak Signal to Noise Ratio (PSNR) and reducing computing time. Being
      compared with the other existing methods, its PSNR distinctly exceeds that of the
      traditional Ghost Imaging (GI) and Differential Ghost Imaging (DGI). In
      comparison with the Compressive-sensing Ghost Imaging (CGI), the computing time
      is substantially shortened, and in regard to PSNR our method exceeds CGI on
      grayscale images and performs as well as CGI visually on binary images. The
      influence of both the detection noise and the accuracy of measurement matrix on
      PSNR are also presented. 

PMID- 25606937
TI  - Deep-sea low-light radiometer system.
AB  - Two single-waveband low-light radiometers were developed to characterize
      properties of the underwater light field relevant to biological camouflage at
      mesopelagic ocean depths. Phenomena of interest were vertical changes in downward
      irradiance of ambient light at wavelengths near 470 nm and 560 nm, and flashes
      from bioluminescent organisms. Depth profiles were acquired at multiple deep
      stations in different geographic regions. Results indicate significant irradiance
      magnitudes at 560 nm, providing direct evidence of energy transfer as described
      by Raman scattering. Analysis of a night profile yielded multiple examples of
      bioluminescent flashes. The selection of high-sensitivity, high-speed silicon
      photomultipliers as detectors enabled measurement of spectrally-resolved
      irradiance to greater than 400 m depth. 

PMID- 25606938
TI  - Thermal effects in thin-film organic solid-state lasers.
AB  - With the recent development of organic solid-state lasers (OSSLs) architectures
      enabling power scaling and progresses towards continuous-wave operation, the
      question of thermal effects now arises in OSSLs. In this paper, a Rhodamine 640
      PMMA based vertical external cavity surface emitting organic laser is
      investigated. A thermal microscope is used to record temperature maps at the
      organic thin film surface during laser action; those maps are compared with time
      resolved finite element thermal simulations. The measured and simulated peak
      temperature rises are in good accordance and are shown to remain below 10 K in
      standard operating conditions, showing a negligible impact on performance. The
      validated model is used to investigate typical OSSL structures from the
      literature, in a virtual high average power regime, and up to the CW regime. It
      is shown that whenever true CW organic lasing will be realized, significant
      thermal effects will have to be considered and properly managed. 

PMID- 25606939
TI  - Tunable subwavelength photonic lattices and solitons in periodically patterned
      graphene monolayer.
AB  - We study linear and nonlinear mode properties in a periodically patterned
      graphene sheet. We demonstrate that a subwavelength one-dimensional photonic
      lattice can be defined across the graphene monolayer, with its modulation depth
      and correspondingly the associated photonic band structures being controlled
      rapidly, by an external gate voltage. We find the existences of graphene lattice
      solitons at the deep-subwavelength scales in both dimensions, thanks to the
      combination of graphene intrinsic self-focusing nonlinearity and the graphene
      plasmonic confinement effects. 

PMID- 25606940
TI  - Dissipative Raman solitons.
AB  - A new type of dissipative solitons--dissipative Raman solitons--are revealed on
      the basis of numerical study of the generalized complex nonlinear Ginzburg-Landau
      equation. The stimulated Raman scattering significantly affects the energy
      scalability of the dissipative solitons, causing splitting to multiple pulses. We
      show, that an appropriate increase of the group-delay dispersion can suppress the
      multipulsing instability due to formation of the dissipative Raman soliton, which
      is chirped, has a Stokes-shifted spectrum, and chaotic modulation on its trailing
      edge. The strong perturbation of a soliton envelope caused by the stimulated
      Raman scattering confines the energy scalability preventing the so-called
      dissipative soliton resonance. We show, that in practical implementations, a
      spectral filter can extend the stability regions of high-energy pulses.

PMID- 25606942
TI  - Bilateral symmetry breaking in nonlinear circular cylinders.
AB  - Symmetry breaking is a common phenomenon in nonlinear systems, it refers to the
      existence of solutions that do not preserve the original symmetries of the
      underlying system. In nonlinear optics, symmetry breaking has been previously
      investigated in a number of systems, usually based on simplified model equations
      or temporal coupled mode theories. In this paper, we analyze the scattering of an
      incident plane wave by one or two circular cylinders with a Kerr nonlinearity,
      and show the existence of solutions that break a lateral reflection symmetry.
      Although symmetry breaking is a known phenomenon in nonlinear optics, it is the
      first time that this phenomenon was rigorously studied in simple systems with one
      or two circular cylinders. 

PMID- 25606943
TI  - Longitudinal fiber parameter measurements of multi-core fiber using OTDR.
AB  - A novel technique is proposed for measuring the longitudinal fiber parameters of
      multi-core fiber (MCF). The mode field diameter (MFD)of a fiber link composed of
      MCF is successfully estimated with a modified optical time domain reflectometer
      (OTDR). The measurement accuracy of the MFD distribution is revealed by
      simulation as a function of the mode coupling coefficient. It is also shown that
      the relative-index difference and chromatic dispersion of MCF can be estimated
      with the present technique. 

PMID- 25606944
TI  - Ag nanoparticles@ZnO nanowire composite arrays: an absorption enhanced UV
      photodetector.
AB  - A novel heterojunction ultraviolet (UV) photodetector of assembling Ag
      nanoparticles (NPs) onto ZnO nanowire (NW) arrays was fabricated via combination
      of chemical vapor deposition and thermal evaporation route. The fabricated
      composite Ag@ZnO NW arrays show blue-shift of UV peaks, suppression of the
      visible peaks, and obvious enhancements in absorption from ultraviolet to
      infrared region and photoluminescence (PL) emission at room-temperature. These
      phenomena are attributed to the Localized Surface Plasmon Resonance (LSPR)
      effect. Benefiting from absorption enhancement and surface heterojunctions,
      Ag@ZnO heterostructures show a photocurrent increment by 117%, a short response
      time of 80 ms and a recovery time of 3.27 s under 365 nm UV illumination of 0.24
      mW/cm2. This research presented a simple route to obtain high performance UV
      photodetectors and would be of some benefit in optical-electron devices
      manufacture.

PMID- 25606945
TI  - Analysis of the THz response of a simple periodic graphite-based structure.
AB  - We report the observation of the dichroism effect in simple wire grid structures
      made of graphite on a paper substrate, i.e. we investigate the feasibility of
      drawing polarizers for the THz band using conventional graphite-based lead
      pencils. The displacement of the maximum frequency of the selective absorption
      phenomenon by varying the wire pitch hints at a polarizing behavior. Measurements
      of the maximum and minimum of transmission efficiency, extinction ratio and
      degree of polarization are carried out with a transmission fiber THz-TDS setup.
      Experimental results show a 9 dB extinction ratio for an inexpensive (<1$) home
      made component. 

PMID- 25606946
TI  - Enhanced transmission due to antireflection coating layer at surface plasmon
      resonance wavelengths.
AB  - We present experiments and analysis on enhanced transmission due to dielectric
      layer deposited on a metal film perforated with two-dimensional periodic array of
      subwavelength holes. The Si3N4 overlayer is applied on the perforated gold film
      (PGF) fabricated on GaAs substrate in order to boost the transmission of light at
      the surface plasmon polariton (SPP) resonance wavelengths in the mid- and long
      wave IR regions, which is used as the antireflection (AR) coating layer between
      two dissimilar media (air and PGF/GaAs). It is experimentally shown that the
      transmission through the perforated gold film with 1.8 um (2.0 um) pitch at the
      first-order (second-order) SPP resonance wavelengths can be increased up to 83%
      (110%) by using a 750 nm (550 nm) thick Si3N4 layer. The SPP resonance leads to a
      dispersive resonant effective permeability (MUeff ? 1) and thereby the refractive
      index matching condition for the conventional AR coating on the surface of a
      dielectric material cannot be applied to the resonant PGF structure. We develop
      and demonstrate the concept of AR condition based on the effective parameters of
      PGF. In addition, the maximum transmission (zero reflection) condition is
      analyzed numerically by using a three-layer model and a transfer matrix method is
      employed to determine the total reflection and transmission. The numerically
      calculated total reflection agrees very well with the reflection obtained by 3D
      full electromagnetic simulations of the entire structure. Destructive
      interference conditions for amplitude and phase to get zero reflection are well
      satisfied.

PMID- 25606947
TI  - Generation and elimination of polarization-dependent ablation of cubic crystals
      by femtosecond laser radiation.
AB  - We experimentally showed that the pi/2-period oscillation of an ablation area
      with laser polarization direction can be observed in GaAs, ZnSe, MgO and LiF with
      cubic crystal by a femtosecond laser (800 nm, 100 fs) and that the modulation in
      the ablation area can be controlled by the laser fluence. While the polarization
      dependence is sustained in a wide range of laser fluences for a narrow band-gap
      crystal, it is strongly suppressed with a slight augmentation of laser fluence in
      a wide band-gap material. The polarization-dependent ablation is explained by the
      crystal's orientation-dependent reduced-electron mass and the resultant
      contrasting nonlinear absorptions with slightly different reduced electron mass.
      The interplay between photoionization and avalanche ionization is discussed to
      interpret the influence of laser fluence on polarization-dependent ablation.
      Based on Keldysh's theory, polarization-dependent ablation occurs in a mixed
      regime between tunneling and multiphoton ionization. 

PMID- 25606948
TI  - Tunable THz absorption in graphene-based heterostructures.
AB  - We investigate THz absorption properties of graphene-based heterostructures by
      using characteristics matrix method based on conductivity. We demonstrate that
      the proposed structure can lead to perfect THz absorption because of strong
      photon localization in the defect layer of the heterostructure. The THz
      absorption may be tuned continuously from 0 to 100% by controlling the chemical
      potential through a gate voltage. By adjusting the incident angle or the period
      number of the two PCs with respect to the graphene layer, one can tailor the
      maximum THz absorption value. The position of the THz absorption peaks can be
      tuned by changing either the center wavelength or the thicknesses ratio of the
      layers constituting the heterostructure. Our proposal may have potentially
      important applications in optoelectronic devices. 

PMID- 25606949
TI  - Relation of the angular momentum of surface modes to the position of their power
      flow center.
AB  - We show that the value of the total angular momentum (AM) carried by a surface
      mode can be interpreted as representing the transverse position of the center or
      balance point of the power flow through the mode. Especially in the lossless
      cases, the value of the Abraham AM per unit power (multiplied by the square of
      the speed of light in vacuum) is exactly the same as the transverse position of
      this power-flow center. However, the Minkowski counterpart becomes proportional
      to that position with a coefficient in the form of 1 + eta, where eta is
      determined mainly by the constitutive parameters of media. 

PMID- 25606950
TI  - Enhanced conductivity of sol-gel silica cladding for efficient poling in electro
      optic polymer/TiO2 vertical slot waveguide modulators.
AB  - We report the enhanced conductivity of sol-gel silica under-cladding for
      efficient poling of electro-optic (EO) polymer in a hybrid EO polymer/TiO2
      vertical slot waveguide modulator. The electrical volume conductivity of sol-gel
      silica cladding increases approximately 30 times when the calcining time of the
      cladding layer is critically reduced to 45 minutes, which increases the in-device
      EO coefficient of the 600-nm-thick EO polymer film in modulators and reduces the
      lower halfwave voltage (Vpi) of the modulators. The lowest driving voltage (Vpi)
      of the TiO2 slot waveguide modulator is 2.0 V for an electrode length (Le) of 10
      mm and wavelength of 1550 nm (VpiLe = 2.0 V.cm) for the low-index guest-host EO
      polymer SEO125. The optical propagation loss is reduced to 7 dB/cm.

PMID- 25606951
TI  - Non-iterative holographic axial localization using complex amplitude of
      diffraction-free vortices.
AB  - We present a novel technique of digital holography using digitally implemented
      diffraction-free vortices for a precise three-dimensional (3D) localization of
      point-like objects. The localization is realized by the processing of the
      holographic image reconstructed at arbitrarily selected plane. Separating a
      single radial component of the spatial spectrum and modulating its phase by a
      virtual spiral mask, the holographic images of individual object points are
      transformed to the image structures analogous to the diffraction-free vortex
      beams. The real part of the complex amplitude of the digital vortices creates the
      shape-invariant patterns rotating due to a defocusing. Determining the angular
      rotation, the axial positions of the individual point objects are specified over
      a wide axial range. In the proposed method, a single in-line hologram is
      processed without phase shifting and multiplane reconstruction, so that a dynamic
      localization and tracking of particles becomes possible. The principle of the
      method is presented in a unified computational model valid for both coherent and
      incoherent techniques of digital holography. The functionality of the method has
      been verified in experiments of the Fresnel incoherent correlation holography
      (FINCH) and its flexibility presented by controlled variations of the
      localization sensitivity. The application potential has been demonstrated by the
      defocusing image rotation of fixed fluorescent microspheres and the 3D
      localization and tracking of moving polystyrene beads resulting in the trajectory
      reconstruction of a selected particle. 

PMID- 25606952
TI  - A novel tunable frequency selective surface absorber with dual-DOF for broadband
      applications.
AB  - A novel tunable frequency selective surface (FSS) with dual-degrees of freedom
      (DOF) is presented, and firstly applied to broadband absorber. Based on a simple
      prototype unit cell resonator, an approach for achieving multi-resonances is
      studied. A unit cell pattern with gradient edges is discussed, and variable
      resistor and variable capacitor are introduced to fully utilize its
      characteristic of multi-resonances. Bias line is designed to provide bias voltage
      respectively for two variable devices and provide two operational DOF for FSS.
      Simulation and measurement results both show that the tunable FSS absorber with
      dual-DOF has wideband absorption with the reflectivity below -10 dB in 1-5 GHz
      and with a total thickness of about 10 mm. 

PMID- 25606953
TI  - Observation of electro-activated localized structures in broad area VCSELs.
AB  - We demonstrate experimentally the electro-activation of a localized optical
      structure in a coherently driven broad-area vertical-cavity surface-emitting
      laser (VCSEL) operated below threshold. Control is achieved by electro-optically
      steering a writing beam through a pre-programmable switch based on a
      photorefractive funnel waveguide. 

PMID- 25606954
TI  - Supercontinuum generation at 800 nm in all-normal dispersion photonic crystal
      fiber.
AB  - We have numerically investigated the supercontinuum generation and pulse
      compression in a specially designed all-normal dispersion photonic crystal fiber
      with a flat-top dispersion curve, pumped by typical pulses from state of the art
      Ti:Sapphire lasers at 800 nm. The optimal combination of pump pulse parameters
      for a given fiber was found, which provides a wide octave-spanning spectrum with
      superb spectral flatness (a drop in spectral intensity of ~1.7 dB). With regard
      to the pulse compression for these spectra, multiple-cycle pulses (~8 fs) can be
      obtained with the use of a simple quadratic compressor and nearly single-cycle
      pulses (3.3 fs) can be obtained with the application of full phase compensation.
      The impact of pump pulse wavelength-shifting relative to the top of the
      dispersion curve on the generated SC and pulse compression was also investigated.
      The optimal pump pulse wavelength range was found to be 750 nm < lambdap < 850
      nm, where the distortions of pulse shape are quite small (< -3.3 dB). The
      influences of realistic fiber fabrication errors on the SC generation and pulse
      compression were investigated systematically. We propose that the spectral shape
      distortions generated by fiber fabrication errors can be significantly attenuated
      by properly manipulating the pump.

PMID- 25606955
TI  - Spectral properties of limiting solitons in optical fibers.
AB  - It seems to be self-evident that stable optical pulses cannot be considerably
      shorter than a single oscillation of the carrier field. From the mathematical
      point of view the solitary solutions of pulse propagation equations should loose
      stability or demonstrate some kind of singular behavior. Typically, an unphysical
      cusp develops at the soliton top, preventing the soliton from being too short.
      Consequently, the power spectrum of the limiting solution has a special behavior:
      the standard exponential decay is replaced by an algebraic one. We derive the
      shortest soliton and explicitly calculate its spectrum for the so-called short
      pulse equation. The latter applies to ultra-short solitons in transparent
      materials like fused silica that are relevant for optical fibers. 

PMID- 25606956
TI  - All-optical measurement of elastic constants in nematic liquid crystals.
AB  - In this article we present a new all-optical method to measure elastic constants
      connected with twist and bend deformations. The method is based on the optical
      Freedericksz threshold effect induced by the linearly polarized electro-magnetic
      wave. In the experiment elastic constants are measured of commonly used liquid
      crystals 6CHBT and E7 and two new nematic mixtures with low birefringence. The
      proposed method is neither very sensitive on the variation of cell thickness,
      beam waist or the power of a light beam nor does it need any special design of a
      liquid crystal cell. The experimental results are in good agreement with the
      values obtain by other methods based on an electro-optical effect. 

PMID- 25606957
TI  - Selection of energy optimized pump concepts for multi core and multi mode erbium
      doped fiber amplifiers.
AB  - The selection of an appropriate pump concept has a major impact on amplifier cost
      and power consumption. The energy efficiency of different pump concepts is
      compared for multi core and multi mode active fibers. In preamplifier stages,
      pump power density requirements derived from full C-band low noise WDM operation
      result in superior energy efficiency of direct pumping of individual cores in a
      multi core fiber with single mode pump lasers compared to cladding pumping with
      uncooled multi mode lasers. Even better energy efficiency is achieved by direct
      pumping of the core in multi mode active fibers. Complexity of pump signal
      combiners for direct pumping of multi core fibers can be reduced by deploying
      integrated components. 

PMID- 25606958
TI  - Pulse synchronization system for picosecond pulse-pumped OPCPA with femtosecond
      level relative timing jitter.
AB  - A simple and compact scheme for synchronization of the pump and signal pulses for
      short-pulse OPCPA is demonstrated. Relative timing jitter of 17 fs RMS is
      achieved (1% of the pump pulse duration) and the system remains locked for hours.
      The scheme uses a balanced optical cross correlator to detect relative delays
      between the pump and signal pulses and can be operated with just 10's of MUJ of
      pump energy and pJ-level signal energies. 

PMID- 25606959
TI  - Performance characterization of a broadband vector Apodizing Phase Plate
      coronagraph.
AB  - One of the main challenges for the direct imaging of planets around nearby stars
      is the suppression of the diffracted halo from the primary star. Coronagraphs are
      angular filters that suppress this diffracted halo. The Apodizing Phase Plate
      coronagraph modifies the pupil-plane phase with an anti-symmetric pattern to
      suppress diffraction over a 180 degree region from 2 to 7 lambda/D and achieves a
      mean raw contrast of 10(-4) in this area, independent of the tip-tilt stability
      of the system. Current APP coronagraphs implemented using classical phase
      techniques are limited in bandwidth and suppression region geometry (i.e. only on
      one side of the star). In this paper, we introduce the vector-APP (vAPP) whose
      phase pattern is implemented through the vector phase imposed by the orientation
      of patterned liquid crystals. Beam-splitting according to circular polarization
      states produces two, complementary PSFs with dark holes on either side. We have
      developed a prototype vAPP that consists of a stack of three twisting liquid
      crystal layers to yield a bandwidth of 500 to 900 nm. We characterize the
      properties of this device using reconstructions of the pupil-plane pattern, and
      of the ensuing PSF structures. By imaging the pupil between crossed and parallel
      polarizers we reconstruct the fast axis pattern, transmission, and retardance of
      the vAPP, and use this as input for a PSF model. This model includes aberrations
      of the laboratory set-up, and matches the measured PSF, which shows a raw
      contrast of 10(-3.8) between 2 and 7 lambda/D in a 135 degree wedge. The vAPP
      coronagraph is relatively easy to manufacture and can be implemented together
      with a broadband quarter-wave plate and Wollaston prism in a pupil wheel in high
      contrast imaging instruments. The liquid crystal patterning technique permits the
      application of extreme phase patterns with deeper contrasts inside the dark
      holes, and the multilayer liquid crystal achromatization technique enables
      unprecedented spectral bandwidths for phase-manipulation coronagraphy.

PMID- 25606960
TI  - Characterization of topological charge and orbital angular momentum of shaped
      optical vortices.
AB  - Optical vortices (OV) are usually associated to cylindrically symmetric light
      beams. However, they can have more general geometries that extends their
      applicability. Since the typical experimental characterization methods are not
      appropriate for OV with arbitrary shapes, we discuss in this work how the
      definitions of the classical orbital angular momentum and the topological charge
      can be used to retrieve these informations in the general case. The concepts
      discussed are experimentally demonstrated and may be specially useful in areas
      such as optical tweezers and plasmonics. 

PMID- 25606961
TI  - 240 kW peak power at 266 nm in nonlinear YAl3(BO3)4 single crystal.
AB  - We report the fourth harmonic generation at 266 nm using a type I YAl3(BO3)4
      (YAB) single crystal from a Q-switch microchip laser Nd:YAG/Cr4+:YAG frequency
      doubled with a LiB3O5 (LBO) crystal. 240 kW peak power at 266 nm corresponding to
      a mean conversion efficiency of 12.2% from 532 to 266 nm has been obtained with a
      2.94 mm thick YAB crystal. The influences of optical homogeneity and absorption
      on the conversion efficiency are discussed.

PMID- 25606962
TI  - Temperature sensor based on ladder-level assisted thermal coupling and thermal
      enhanced luminescence in NaYF4: Nd3+.
AB  - NaYF4: Nd3+ microprisms were synthesized by a hydrothermal method. The bands of
      near-infrared (NIR) luminescence originating from the 4F3/2, 4F5/2 and 4F7/2
      levels of Nd3+ ions in NaYF4: Nd3+ microcrystals were measured under 574.8 nm
      excitation at various temperatures from 323 to 673 K. The fluorescence intensity
      ratios (FIRs) between any two of the three bands change monotonically with
      temperature and agree with the prediction assuming thermal couplings. A large
      relative temperature sensitivity of 1.12% K-1 at 500K is reached with the FIR of
      4F7/2 to 4F3/2 levels. In addition, anti-Stokes fluorescence from 4F5/2 level
      (740 nm) and 4F5/2,7/2 levels (740 nm and 803 nm) of Nd3+ ions was studied
      meticulously under 793.8 nm and 864.2 nm excitations, respectively. The
      intensities were shown to be greatly enhanced as temperature increases, and the
      740 nm band from 4F7/2 level at 458 K increases in intensity by 170 fold relative
      to that at 298 K under the 793.8 nm excitation.

PMID- 25606963
TI  - Imaging of acoustic fields using optical feedback interferometry.
AB  - This study introduces optical feedback interferometry as a simple and effective
      technique for the two-dimensional visualisation of acoustic fields. We present
      imaging results for several pressure distributions including those for
      progressive waves, standing waves, as well as the diffraction and interference
      patterns of the acoustic waves. The proposed solution has the distinct advantage
      of extreme optical simplicity and robustness thus opening the way to a low cost
      acoustic field imaging system based on mass produced laser diodes. 

PMID- 25606964
TI  - Iterative tailoring of optical quantum states with homodyne measurements.
AB  - As they can travel long distances, free space optical quantum states are good
      candidates for carrying information in quantum information technology protocols.
      These states, however, are often complex to produce and require protocols whose
      success probability drops quickly with an increase of the mean photon number.
      Here we propose a new protocol for the generation and growth of arbitrary states,
      based on one by one coherent adjunctions of the simple state superposition
      alpha|0> + beta|1>. Due to the nature of the protocol, which allows for the use
      of quantum memories, it can lead to high performances. 

PMID- 25606965
TI  - Electroabsorption-modulated widely tunable DBR laser transmitter for WDM-PONs.
AB  - We present an InP based distributed Bragg reflector (DBR) laser transmitter which
      has a wide wavelength tuning range and a high chip output power for wavelength
      division multiplexing passive optical network (WDM-PON) applications. By butt
      jointing InGaAsP with 1.45 um emission wavelength as the material of the grating
      section, the laser wavelength can be tuned for over 13 nm by the DBR current.
      Accompanied by varying the chip temperature, the tuning range can be further
      enlarged to 16 nm. With the help of the integrated semiconductor optical
      amplifier (SOA), the largest chip output power is over 30 mW. The
      electroabsorption modulator (EAM) is integrated into the device by the selective
      area growth (SAG) technique. The 3 dB small signal modulation bandwidth of the
      EAM is over 13 GHz. The device has both a simple tuning scheme and a simple
      fabrication procedure, making it suitable for low cost massive production which
      is desirable for WDM-PON uses.

PMID- 25606966
TI  - Mode-resolved gain analysis and lasing in multi-supermode multi-core fiber laser.
AB  - Multi-core fibers (MCFs) with coupled-cores are attractive large-mode area (LMA)
      specialty fiber designs that support the propagation of a few transverse modes
      often called supermodes (SMs). Compared to other LMA fibers, the uniqueness of
      MCF arises from the higher degrees of design space offered by a multitude of core
      array geometries, resulting in extended flexibility to tailor SM properties. To
      date, the use of MCF as gain media has focused on lasers that operate in only one
      selected SM, typically the lowest order in-phase SM, which considerably limited
      the potential of these multi-core structures. Here, we expand the potential of
      MCF lasers by investigating multi-SM amplification and lasing schemes. Amplifier
      and laser systems using a 7 coupled-cores Yb-doped MCF as gain medium were
      successfully designed and assembled. Individual SM could be decomposed using the
      correlation filter technique mode analysis and the modal amplification factors
      (gammai) were recorded. With access to amplification characteristics of
      individual transverse modes, a monolithic MCF laser was demonstrated that
      operates simultaneously on the two SMs carrying the highest optical gain.

PMID- 25606967
TI  - Stress compensation with antireflection coatings for ultrafast laser
      applications: from theory to practice.
AB  - Each complicated coating, in particular, a dispersive mirror consists of dozens
      of layers. Thin films layers have mechanical stresses. After summing up stresses
      from all layers, the resulting stress is high enough to bend even a relatively
      thick substrate. To avoid this effect we suggest depositing an antireflection
      coating (AR) at the back-side of the substrate which together with suppression of
      unwanted reflections from the back side will also compensate this stress. We
      demonstrate unique, extremely thick and sophisticated AR coating consisting of 71
      layers with the total physical thickness of 7.5 um. This AR coating completely
      compensates stress from the dispersive mirror coated on the front side and
      minimizes unwanted reflections. 

PMID- 25606968
TI  - Melatonin induces apoptosis in cholangiocarcinoma cell lines by activating the
      reactive oxygen species-mediated mitochondrial pathway.
AB  - We previously demonstrated that melatonin could be used as a chemopreventive
      agent for inhibiting cholangiocarcinoma (CCA) development in a hamster model.
      However, the cytotoxic activity of melatonin in cancer remains unclear. In the
      present study, we investigated the effect of melatonin on CCA cell lines. Human
      CCA cell lines (KKU-M055 and KKU-M214) were treated with melatonin at
      concentrations of 0.5, 1 and 2 mM for 48 h. Melatonin treatment exerted a
      cytotoxic effect on CCA cells by inhibiting CCA cell viability in a concentration
      dependent manner. Treatment with melatonin, especially at 2 mM, increased
      intracellular reactive oxygen species (ROS) production and in turn led to
      increased oxidative DNA damage and 8-oxodG formation. Moreover, melatonin
      treatment enhanced the production of cytochrome c leading to apoptosis in a
      concentration-dependent manner, as indicated by increased expression of apoptosis
      related proteins caspase-3 and caspase-7. In conclusion, melatonin acts as a pro
      oxidant by activating ROS-dependent DNA damage and thus leading to the apoptosis
      of CCA cells.

PMID- 25606969
TI  - Inhibitory effect of arazyme on the development of atopic dermatitis-like lesions
      in BALB/c and Nc/Nga mice.
AB  - Arazyme is a metalloprotease released by Aranicola proteolyticus that was shown
      to inhibit cytokine release in HaCaT and endothelial cells. However, the
      regulatory effects of arazyme in atopic dermatitis remain to be fully understood.
      In the present study, the anti-inflammatory effects of arazyme in BALB/c and
      Nc/Nga mice induced with 2,4-dinitrochlrobenzene (DNCB) were investigated. BALB/c
      mice were sensitized with DNCB and were subsequently administered arazyme for 4
      weeks either orally, dorsally or orally/dorsally. Arazyme administration
      significantly reduced epidermal thickening and infiltration of inflammatory cells
      into the dermis compared with the DNCB group. However, serum immunoglobulin E
      (IgE) levels were not altered by arazyme treatment. Additionally, the level of
      secretion of interleukins (IL)-4, -5 and -13 in the splenocytes of BALB/c mice
      was elevated following stimulation with concanavalin A, while the increase of IL
      4 and IL-13 was inhibited by arazyme. Administration of arazyme (25 mg/kg in
      phosphate-buffered saline) to Nc/Nga mice that had been sensitized with DNCB for
      6 weeks reduced the skin severity score compared with that in the DNCB group and
      inhibited the histological manifestations of atopic dermatitis-like skin lesions.
      In addition, the serum IgE levels were reduced in the arazyme-treated NC/Nga mice
      relative to the DNCB group. Collectively, these results indicated that arazyme
      attenuates the development of atopic dermatitis-like lesions via lowering the
      levels of IgE and inflammatory cytokines. The results of the present study will
      aid in the development of effective therapeutic strategies for the treatment of
      allergic diseases, including atopic dermatitis.

PMID- 25606970
TI  - HIV-1 replication and the cellular eukaryotic translation apparatus.
AB  - Eukaryotic translation is a complex process composed of three main steps:
      initiation, elongation, and termination. During infections by RNA- and DNA
      viruses, the eukaryotic translation machinery is used to assure optimal viral
      protein synthesis. Human immunodeficiency virus type I (HIV-1) uses several non
      canonical pathways to translate its own proteins, such as leaky scanning,
      frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates
      the host translation machinery by targeting key translation factors and overcomes
      different cellular obstacles that affect protein translation. In this review, we
      describe how HIV-1 proteins target several components of the eukaryotic
      translation machinery, which consequently improves viral translation and
      replication. 

PMID- 25606971
TI  - Usutu virus: an emerging flavivirus in Europe.
AB  - Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the
      Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley
      encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was
      discovered in South Africa in 1959. In Europe, the first true demonstration of
      circulation of USUV was reported in Austria in 2001 with a significant die-off of
      Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring
      countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland,
      England, Czech Republic, Greece, and Belgium, where it caused unusual mortality
      in birds. In 2009, the first two human cases of USUV infection in Europe have
      been reported in Italy, causing meningoencephalitis in immunocompromised
      patients. This review describes USUV in terms of its life cycle, USUV
      surveillance from Africa to Europe, human cases, its cellular tropism and
      pathogenesis, its genetic relationship with other flaviviruses, genetic diversity
      among USUV strains, its diagnosis, and a discussion of the potential future
      threat to Asian countries. 

PMID- 25606972
TI  - Identification of a novel human rhinovirus C type by antibody capture VIDISCA
      454.
AB  - Causative agents for more than 30 percent of respiratory infections remain
      unidentified, suggesting that unknown respiratory pathogens might be involved. In
      this study, antibody capture VIDISCA-454 (virus discovery cDNA-AFLP combined with
      Roche 454 high-throughput sequencing) resulted in the discovery of a novel type
      of rhinovirus C (RV-C). The virus has an RNA genome of at least 7054 nt and
      carries the characteristics of rhinovirus C species. The gene encoding viral
      protein 1, which is used for typing, has only 81% nucleotide sequence identity
      with the closest known RV-C type, and, therefore, the virus represents the first
      member of a novel type, named RV-C54. 

PMID- 25606973
TI  - A polyprotein-expressing salmonid alphavirus replicon induces modest protection
      in atlantic salmon (Salmo salar) against infectious pancreatic necrosis.
AB  - Vaccination is an important strategy for the control and prevention of infectious
      pancreatic necrosis (IPN) in farmed Atlantic salmon (Salmo salar) in the post
      smolt stage in sea-water. In this study, a heterologous gene expression system,
      based on a replicon construct of salmonid alphavirus (SAV), was used for in vitro
      and in vivo expression of IPN virus proteins. The large open reading frame of
      segment A, encoding the polyprotein NH2-pVP2-VP4-VP3-COOH, as well as pVP2, were
      cloned and expressed by the SAV replicon in Chinook salmon embryo cells (CHSE
      214) and epithelioma papulosum cyprini (EPC) cells. The replicon constructs
      pSAV/polyprotein (pSAV/PP) and pSAV/pVP2 were used to immunize Atlantic salmon
      (Salmo salar) by a single intramuscular injection and tested in a subsequent IPN
      virus (IPNV) challenge trial. A low to moderate protection against IPN was
      observed in fish immunized with the replicon vaccine that encoded the pSAV/PP,
      while the pSAV/pVP2 construct was not found to induce protection. 

PMID- 25606975
TI  - Autologous fat grafting in the treatment of fibrotic perioral changes in patients
      with systemic sclerosis.
AB  - Autologous fat tissue grafting (AFTG) has been successfully used in the treatment
      of different sclerotic conditions, including localized scleroderma. Patients with
      advanced systemic sclerosis (SSc)-related perioral thickening and mouth opening
      limitation are candidates for this therapeutic approach. AFTG of the lips was
      performed to improve mouth opening in patients with SSc. We enrolled in the study
      20 female patients with diffuse SSc (median age 35 +/- 15 years and 11 +/- 10
      years of disease duration). Two-milliliter fractions of autologous fat drawn from
      trochanteric or periumbilical areas were injected in eight different sites around
      the mouth. Baseline and after-treatment mouth opening changes were assessed by
      measuring interincisal distance and oral perimeter, while skin hardness was
      tested by digital durometer. Pre- and posttreatment modifications of
      microvascular architecture were assessed by counting capillaries in the inferior
      lip videocapillaroscopy (VC) images and by scoring the microvascular density
      (MVD) in anti-CD34/CD31 immunohistochemical (IH) stained perioral skin biopsy
      sections. Similarly, histological sections were examined to evaluate
      dermoepidermic junction (DEJ) modifications. Three months after treatment, both
      the interincisal distance and oral perimeter significantly increased (p < 0.001).
      At the same time, a significant skin neovascularization became evident, both
      considering the VC images (p < 0.001) and MVD scores in IH sections (p < 0.0001).
      Finally, some skin histological aspects also improved, as shown by the
      significant changes in DEJ flattening scores (p < 0.0001). The present study
      suggests that, in patients with SSc, AFTG can improve mouth opening and function,
      induce a neovascularization, and partially restore the skin structure.

PMID- 25606974
TI  - Bacteriophage-derived vectors for targeted cancer gene therapy.
AB  - Cancer gene therapy expanded and reached its pinnacle in research in the last
      decade. Both viral and non-viral vectors have entered clinical trials, and
      significant successes have been achieved. However, a systemic administration of a
      vector, illustrating safe, efficient, and targeted gene delivery to solid tumors
      has proven to be a major challenge. In this review, we summarize the current
      progress and challenges in the targeted gene therapy of cancer. Moreover, we
      highlight the recent developments of bacteriophage-derived vectors and their
      contributions in targeting cancer with therapeutic genes following systemic
      administration. 

PMID- 25606976
TI  - Revealing gene clusters associated with the development of cholangiocarcinoma,
      based on a time series analysis.
AB  - Cholangiocarcinoma (CC) is a rapidly lethal malignancy and currently is
      considered to be incurable. Biomarkers related to the development of CC remain
      unclear. The present study aimed to identify differentially expressed genes
      (DEGs) between normal tissue and intrahepatic CC, as well as specific gene
      expression patterns that changed together with the development of CC. By using a
      two-way analysis of variance test, the biomarkers that could distinguish between
      normal tissue and intrahepatic CC dissected from different days were identified.
      A k-means cluster method was used to identify gene clusters associated with the
      development of CC according to their changing expression pattern. Functional
      enrichment analysis was used to infer the function of each of the gene sets. A
      time series analysis was constructed to reveal gene signatures that were
      associated with the development of CC based on gene expression profile changes.
      Genes related to CC were shown to be involved in 'mitochondrion' and 'focal
      adhesion'. Three interesting gene groups were identified by the k-means cluster
      method. Gene clusters with a unique expression pattern are related with the
      development of CC. The data of this study will facilitate novel discoveries
      regarding the genetic study of CC by further work.

PMID- 25606977
TI  - Anti-HIV Nucleoside Phosphonate GS-9148 and Its Prodrug GS-9131: Scale Up of a 2'
      F Modified Cyclic Nucleoside Phosphonate and Synthesis of Selected Amidate
      Prodrugs.
AB  - Nucleoside phosphonate analogs are an important class of antiviral drugs for the
      treatment of HIV and HBV. The most recent nucleoside phosphonate to progress to
      clinical development is GS-9131, a cyclic nucleoside phosphonate (CNP). This unit
      contains procedures for the synthesis of the parent CNP 2'-Fd4AP (GS-9148) and
      selected monoamidate and bisamidate prodrugs, including the monoamidate clinical
      prodrug GS-9131. The first basic protocol of this unit details improved
      procedures for the preparation of 2'-Fd4AP and related phosphonate esters by
      introduction of a hydroxylmethyl phosphonate ester regioselectively and
      stereoselectively onto a furanose core via a glycal intermediate. The method
      described is believed to be robust and flexible, allowing for a variety of
      analogs with other nucleobases or furanose 2'-ring substitutions to be prepared.
      The preparation of monoamidate and bisamidate prodrugs either on the phosphonate
      diacid or its monophenyl ester is then described in the second and third basic
      protocols of this unit.

PMID- 25606978
TI  - Synthesis of 8-oxoguanosine phosphoramidite and its incorporation into
      Oligoribonucleotides..
AB  - The detailed synthetic protocol for preparation of the phosphoramidite of an
      oxidatively damaged ribonucleotide, 8-oxoguanosine (8-oxo-G), and its
      incorporation into RNA are described. The O(6)- and N(7)-bisdiphenylcarbamoyl
      protected 8-oxoguanosine phosphoramidite was synthesized as a new phosphoramidite
      precursor unit for the synthesis of RNA. It was successfully incorporated into
      the RNA sequences, and the synthesized RNAs were completely deprotected with 28%
      aqueous ammonia solution at 55 degrees C for 24 hr. After purification using
      HPLC, they were identified by MALDI-TOF mass measurement. The base-pairing
      properties showed that 8-oxo-G forms base pairs not only with rC or dC in anti
      conformation, but also with rA in syn conformation within the RNA duplexes or
      RNA/DNA heteroduplexes.

PMID- 25606979
TI  - Synthesis of G-N2-(CH2)3-N2-G Trimethylene DNA Interstrand Cross-Links.
AB  - The synthesis of G-N(2)-(CH(2))(3)-N(2)-G trimethylene DNA interstrand cross
      links (ICLs) in a 5'-CG-3' and 5'-GC-3' sequence from oligodeoxynucleotides
      containing N(2)-(3-aminopropyl)-2'-deoxyguanosine and 2-fluoro-O(6)
      (trimethylsilylethyl)inosine is presented. Automated solid-phase DNA synthesis
      was used for unmodified bases and modified nucleotides were incorporated via
      their corresponding phosphoramidite reagent by a manual coupling protocol. The
      preparation of the phosphoramidite reagents for incorporation of N(2)-(3
      aminopropyl)-2'-deoxyguanosine is reported. The high-purity trimethylene DNA
      interstrand cross-link product is obtained through a nucleophilic aromatic
      substitution reaction between the N(2)-(3-aminopropyl)-2'-deoxyguanosine- and 2
      fluoro-O(6)-(trimethylsilylethyl)inosine-containing oligodeoxynucleotides.

PMID- 25606980
TI  - Molecular modeling of nucleic Acid structure: setup and analysis.
AB  - The last in a set of units by the same authors, this unit addresses some
      important remaining questions about molecular modeling of nucleic acids. The unit
      describes how to choose an appropriate molecular mechanics force field; how to
      set up and equilibrate the system for accurate simulation of a nucleic acid in an
      explicit solvent by molecular dynamics or Monte Carlo simulation; and how to
      analyze molecular dynamics trajectories.

PMID- 25606982
TI  - Genome-wide gene expression profiling of ischemia-reperfusion injury in rat
      kidney, intestine and skeletal muscle implicate a common involvement of MAPK
      signaling pathway.
AB  - The mechanisms of ischemia-reperfusion (I/R) injury have not been fully
      elucidated to date. In order to determine the genetic involvement across
      different organs during I/R injury, a DNA microarray approach was used to analyze
      the gene expression profiles of the kidney, intestine, and skeletal muscle in a
      rat model of I/R injury. Fifteen male Lewis rats were divided randomly into three
      different organ groups; a sham operation (control group), 60-min-ischemia (Is
      group) only, and 60-min-ischemia plus 60-min-reperfusion (I/R group),
      respectively. The target genes were identified by DNA microarray and studied by
      quantitative polymerase chain reaction (qPCR). By comparing the I/R group with
      the control group, a 2-fold upregulation of 467, 172, and 3932 and a 2-fold
      downregulation of 437, 416, and 4203 genes were identified in the kidney, small
      intestine, and skeletal muscle, respectively. Several commonly upregulated genes
      associated with mitogen-activated protein kinase (MAPK) pathways, including Jun,
      Atf3, junB, Fos, Adm and Dusp 1, were differentially expressed in the I/R group.
      The mRNA expression levels of the target genes were confirmed by qPCR. The
      present study hypothesized that the MAPK pathway may function in a common pathway
      of I/R injury and regulate the pathogenesis through activator protein 1. The
      findings of the present study contributed to the understanding of the molecular
      pathways associated with I/R injury.

PMID- 25606983
TI  - Is the injury gap closing between the Aboriginal and general populations of
      British Columbia?
AB  - BACKGROUND: Evidence from various jurisdictions has shown higher rates of injury
      for Aboriginal compared with non-Aboriginal populations. This study provides an
      overview of trends in hospitalization injury rates between the Aboriginal and
      total populations of one Canadian province, British Columbia. DATA AND METHODS:
      Hospital discharge records from 1986 through 2010 were obtained from linked
      health care databases maintained by Population Data BC. Crude rates and
      standardized relative risks of hospitalization due to injury among Aboriginal
      people, relative to the total population of British Columbia, were calculated.
      Changes over time among males and females were compared for various types and
      causes of injury. RESULTS: Throughout more than two decades, standardized risks
      of hospitalization for injury decreased among the Aboriginal and total
      populations of British Columbia. Larger decreases among the Aboriginal population
      than among the total population suggest that the gaps are closing. Downward
      trends in rates were found for most injury categories, and for males and females.
      INTERPRETATION: The findings indicate narrowing of the gap in injury rates
      between the total population of British Columbia and the province's Aboriginal
      population.

PMID- 25606981
TI  - In vitro selection using modified or unnatural nucleotides.
AB  - Incorporation of modified nucleotides into in vitro RNA or DNA selections offers
      many potential advantages, such as the increased stability of selected nucleic
      acids against nuclease degradation, improved affinities, expanded chemical
      functionality, and increased library diversity. This unit provides useful
      information and protocols for in vitro selection using modified nucleotides. It
      includes a discussion of when to use modified nucleotides; protocols for
      evaluating and optimizing transcription reactions, as well as confirming the
      incorporation of the modified nucleotides; protocols for evaluating modified
      nucleotide transcripts as template in reverse transcription reactions; protocols
      for the evaluation of the fidelity of modified nucleotides in the replication and
      the regeneration of the pool; and a protocol to compare modified nucleotide pools
      and selection conditions.

PMID- 25606984
TI  - Chronic pain, activity restriction and flourishing mental health.
AB  - BACKGROUND: According to the activity restriction (AR) model, a potential
      explanation for the impact of chronic pain on mental illness is that pain
      contributes to depression by limiting usual activities. This study uses a measure
      of mental health (flourishing), rather than mental illness to examine
      associations between pain and activity restrictions. DATA AND METHODS: Data from
      the 2011/2012 Canadian Community Health Survey were used to study the
      relationship between pain intensity, pain-related activity prevention, and
      flourishing mental health in people aged 18 or older. Multivariate logistic
      regression was used in a sample of 26,429 people with chronic pain to identify
      significant relationships, while adjusting for potential confounders. RESULTS: In
      2011/2012, an estimated 6 million Canadians aged 18 or older (22%) reported
      chronic pain. They were less likely to be in flourishing mental health than were
      people without chronic pain (69% versus 79%). The prevalence of flourishing
      mental health declined as pain intensity and the number of activities prevented
      because of pain increased. Pain intensity and pain-related activity prevention
      were each independently associated with flourishing mental health, even when
      socio-demographic and health factors were taken into account. Pain-related
      activity prevention partially mediated the association between pain intensity and
      flourishing mental health. INTERPRETATION: The results of this study support the
      AR model and highlight the importance of both pain intensity and activity
      restriction in relation to flourishing mental health.

PMID- 25606986
TI  - Energy-resolved visibility analysis of grating interferometers operated at
      polychromatic X-ray sources.
AB  - Grating interferometry has been successfully adapted at standard X-ray tubes and
      is a promising candidate for a broad use of phase-contrast imaging in medical
      diagnostics or industrial testing. The achievable image quality using this
      technique is mainly dependent on the interferometer performance with the
      interferometric visibility as crucial parameter. The presented study deals with
      experimental investigations of the spectral dependence of the visibility in order
      to understand the interaction between the single contributing energies.
      Especially for the choice which type of setup has to be preferred using a
      polychromatic source, this knowledge is highly relevant. Our results affirm
      previous findings from theoretical investigations but also show that measurements
      of the spectral contributions to the visibility are necessary to fully
      characterize and optimize a grating interferometer and cannot be replaced by only
      relying on simulated data up to now. 

PMID- 25606987
TI  - Evidence for frequency comb emission from a Fabry-Perot terahertz quantum-cascade
      laser.
AB  - We report on a broad-band terahertz quantum-cascade laser (QCL) with a long Fabry
      Perot ridge cavity, for which the tuning range of the individual laser modes
      exceeds the mode spacing. While a spectral range of approximately 60 GHz (2 cm(
      1)) is continuously covered by current and temperature tuning, the total emission
      range spans more than 270 GHz (9 cm(-1)). Within certain operating ranges, we
      found evidence for stable frequency comb operation of the QCL. An experimental
      technique is presented to characterize frequency comb operation, which is based
      on the self-mixing effect.

PMID- 25606988
TI  - Megawatt peak power level sub-100 fs Yb:KGW oscillators.
AB  - We report on the first demonstration, to the best of our knowledge, of sub-100 fs
      pulses directly from the diode-pumped mode-locked Yb:KGW bulk oscillators
      operated at a low repetition rate. The 36 MHz oscillator delivered 78 fs pulses
      with pulse energy of 50 nJ and peak power of 0.65 MW. The cavity was extended by
      inserting a 1:1 imaging telescope, allowing 85 fs pulses to be generated at a
      repetition rate of 18 MHz. The pulse energy up to 83 nJ was reached,
      corresponding to a peak power as high as 1 MW. Sub-100 fs regime was achieved by
      dual action of the Kerr-lens and saturable absorber (KLAS) mode locking. 

PMID- 25606985
TI  - Functional properties of bone marrow derived multipotent mesenchymal stromal
      cells are altered in heart failure patients, and could be corrected by adjustment
      of expansion strategies.
AB  - BACKGROUND: Bone marrow multipotent mesenchymal stromal cells (BM-MMSC)
      considered as a prospective substrate for cell therapy applications, however
      adult stem cells could be affected by donor-specific factors: age, gender,
      medical history. Our aim was to investigate how HF affects the functional
      properties of BM-MMSC. MATERIALS AND METHODS: BM-MMSC from 10 healthy donors
      (HD), and 16 donors with chronic HF were evaluated for proliferative activity,
      ability to differentiate, replicative senescence, expression of genes that affect
      regeneration and fibrosis. The effect of culturing conditions on efficiency of BM
      MMSC expansion was determined. RESULTS: HF-derived BM-MMSC demonstrated early
      decrease of proliferative activity and upregulation of genes that control both,
      regeneration and fibrosis: Tgf-beta pathway, synthesis of ECM, remodeling
      enzymes, adhesion molecules. We assume that these effects were related to
      increase of frequency of myofibroblast-like CD146+/SMAalpha+ CFU-F in HF samples;
      (ii) low seeding density and hypoxia resulted in predominant purification and
      expansion of CD146+/SMAalpha- CFU-Fs. (iii) the activity of NPs system was
      downregulated in HF BM-MMSC; CONCLUSIONS: downregulation of NP signaling in
      combination with upregulation of Tgf-beta pathway in BM-MMSC would result in pro
      fibrotic phenotype and make these cells non-effective for therapeutic
      applications; the corrections in culturing strategy resulted in 2(3)-2(7)
      increase of expansion efficiency.

PMID- 25606989
TI  - Tapered GRIN fiber microsensor.
AB  - The sensitivity of an optical fiber microsensor based on inter-modal interference
      can be considerably improved by tapering a short extension of the multimode
      fiber. In the case of Graded Index fibers with a parabolic refractive index
      profile, a meridional ray exhibits a sinusoidal path. When these fibers are
      tapered, the period of the propagated beam decrease down-taper and increase up
      taper. We take advantage of this modulation -along with the enhanced overlap
      between the evanescent field and the external medium- to substantially increase
      the sensitivity of these devices by tuning the sensor's maximum sensitivity
      wavelength. Moreover, the extension of this device is reduced by one order of
      magnitude, making it more propitious for reduced space applications. Numerical
      and experimental results demonstrate the success and feasibility of this
      approach. 

PMID- 25606990
TI  - Optimally-designed single fiber Bragg grating filter scheme for RZ-OOK/DPSK/DQPSK
      to NRZ-OOK/DPSK/DQPSK format conversion.
AB  - We investigate return-to-zero (RZ) to non-return-to-zero (NRZ) format conversion
      by means of the linear time-invariant system theory. It is shown that the problem
      of converting random RZ stream to NRZ stream can be reduced to constructing an
      appropriate transfer function for the linear filter. This approach is then used
      to propose novel optimally-designed single fiber Bragg grating (FBG) filter
      scheme for RZ-OOK/DPSK/DQPSK to NRZ-OOK/DPSK/DQPSK format conversion. The
      spectral response of the FBG is designed according to the optical spectra of the
      algebraic difference between isolated NRZ and RZ pulses, and the filter order is
      optimized for the maximum Q-factor of the output NRZ signals. Experimental
      results as well as simulations show that such an optimally-designed FBG can
      successfully perform RZ-OOK/DPSK/DQPSK to NRZ-OOK/DPSK/DQPSK format conversion.

PMID- 25606991
TI  - Polarization splitter based on dual-core photonic crystal fiber.
AB  - A polarization splitter based on a new type of dual-core photonic crystal fiber
      (DC-PCF) is proposed. The effects of geometrical parameters of the DC-PCF on
      performances of the polarization splitter are investigated by finite element
      method (FEM). The numerical results demonstrate that the polarization splitter
      possesses ultra-short length of 119.1 MUm and high extinction ratio of 118.7 dB
      at the wavelength of 1.55 MUm. Moreover, an extinction ratio greater than 20 dB
      is achieved over a broad bandwidth of 249 nm, i.e., from 1417 nm to 1666 nm,
      covering the S, C and L communication bands. 

PMID- 25606992
TI  - Sensitive detection of yeast using terahertz slot antennas.
AB  - We demonstrated sensitive detection of individual yeast cells and yeast films by
      using slot antenna arrays operating in the terahertz frequency range.
      Microorganisms located at the slot area cause a shift in the resonant frequency
      of the THz transmission. The shift was investigated as a function of the surface
      number density for a set of devices fabricated on different substrates. In
      particular, sensors fabricated on a substrate with relatively low permittivity
      demonstrate higher sensitivity. The frequency shift decreases with increasing
      slot antenna width for a fixed coverage of yeast film, indicating a field
      enhancement effect. Furthermore, the vertical range of the effective sensing
      volume has been studied by varying the thickness of the yeast film. The resonant
      frequency shift saturates at 3.5 MUm for a slot width of 2 MUm. In addition, the
      results of finite-difference time-domain simulations are in good agreement with
      our experimental data. 

PMID- 25606993
TI  - A metamolecule antenna for coplanar waveguides.
AB  - We report on a metamolecule antenna, based on a fish-scale design but augmented
      with two split-ring resonators (SRRs) placed within the fish-scale loops. The
      properties of the antenna resonator, with and without additional SRRs, were
      examined using finite element method simulations (COMSOL Multiphysics). The
      simulation findings were subsequently confirmed experimentally, using a vector
      network analyser coupled to an antenna-loaded coplanar waveguide (CPW). The
      addition of SRRs to the fish-scale meta-molecule leads to a demonstrably large
      increase in microwave-absorption. It is shown that the fish-scale/SRR/CPW
      combination performs as a microwave antenna. Simulations of the antenna gain and
      far-field emission are presented and discussed. 

PMID- 25606994
TI  - Influence of random zone positioning errors on the resolving power of Fresnel
      zone plates.
AB  - Fresnel zone plates produced by electron beam lithography and planar etching
      techniques provide a resolving power of about 10 nm. An alternative zone plate
      fabrication approach is based on alternately coating a micro-wire with two
      different materials. With this process, very thin zone layers with very high
      aspect ratios can be deposited. However, depending on the fabrication method,
      random zone positioning errors may introduce strong aberrations. We simulate the
      effect of positioning errors using different random fluctuations and study their
      influence on zone plate resolution. We find that random errors significantly
      decrease the contrast transfer of X-ray microscopes. Additionally, we derive an
      upper bound for the mean acceptable variance of the deposition rate. 

PMID- 25606995
TI  - Transition between metamaterial and photonic-crystal behavior in arrays of
      dielectric rods.
AB  - Using finite-difference time-domain simulations, we study the interactions of
      electromagnetic radiation with a square array of dielectric rods parallel to the
      electric vector. We observe the electric and magnetic Mie resonances which induce
      intervals of negative effective permittivity and permeability and which
      contribute to the formation of the photonic band gaps. Owing to the interplay of
      these phenomena, a narrow spectral range with a negative refractive index can
      occur. However, this requires the filling fraction of the dielectric to fall into
      a well defined interval of values and its permittivity to exceed a minimum of
      about 50. We discuss these phenomena from the perspective of both photonic
      crystal and metamaterial concepts. 

PMID- 25606996
TI  - High-speed multi-wavelength Fresnel diffraction imaging.
AB  - We demonstrate a compact lensless microscope which can capture video-rate phase
      contrast images of moving objects and allows numerical scanning of the focal
      distance after recording. Using only an RGB-detector and illumination from a
      single mode fiber, diffraction patterns at three wavelengths are recorded
      simultaneously, enabling high-speed data collection and reconstruction of phase
      and amplitude. The technique is used for imaging of a moving test target, beads
      in a flow cell, and imaging of Caenorhabditis elegans moving in a droplet of
      liquid. 

PMID- 25606997
TI  - Retrieval of frequency spectrum from time-resolved spectroscopic data: comparison
      of Fourier transform and linear prediction methods.
AB  - Femtosecond time-resolved signals often display oscillations arising from the
      nuclear and electronic wave packet motions. Fourier power spectrum is generally
      used to retrieve the frequency spectrum. We have shown by numerical simulations
      and coherent phonon spectrum of single walled carbon nanotubes (SWCNT) that the
      Fourier power spectrum may not be appropriate to obtain the spectrum, when the
      peaks overlap with varying phases. Linear prediction singular value decomposition
      (LPSVD) can be a good alternative for this case. We present a robust way to
      perform LPSVD analysis and demonstrate the method for the chirality assignment of
      SWCNT through the time-domain coherent phonon spectroscopy. 

PMID- 25606998
TI  - Variable optical attenuator and dynamic mode group equalizer for few mode fibers.
AB  - Variable optical attenuation (VOA) for three-mode fiber is experimentally
      presented, utilizing an amplitude spatial light modulator (SLM), achieving up to 
      28dB uniform attenuation for all modes. Using the ability to spatially vary the
      attenuation distribution with the SLM, we also achieve up to 10dB differential
      attenuation between the fiber's two supported mode group (LP01 and LP11). The
      spatially selective attenuation serves as the basis of a dynamic mode-group
      equalizer (DME), potentially gain-balancing mode dependent optical amplification.
      We extend the experimental three mode DME functionality with a performance
      analysis of a fiber supporting 6 spatial modes in four mode groups. The spatial
      modes' distribution and overlap limit the available dynamic range and performance
      of the DME in the higher mode count case.

PMID- 25606999
TI  - On-chip optical trapping and Raman spectroscopy using a TripleX dual-waveguide
      trap.
AB  - We present a new approach to the dual-beam geometry for on-chip optical trapping
      and Raman spectroscopy, using waveguides microfabricated in TripleX technology.
      Such waveguides are box shaped and consist of SiO2 and Si3N4, so as to provide a
      low index contrast with respect to the SiO2 claddings and low loss, while
      retaining the advantages of Si3N4. The waveguides enable both the trapping and
      Raman functionality with the same dual beams. Polystyrene beads of 1 MUm diameter
      can be easily trapped with the device. In the axial direction discrete trapping
      positions occur, owing to the intensity pattern of the interfering beams.
      Trapping events are interpreted on the basis of simulated optical fields and
      calculated optical forces. The average transverse trap stiffness is 0.8 pN/nm/W,
      indicating that a strong trap is formed by the beams emitted by the waveguides.
      Finally, we measure Raman spectra of trapped beads for short integration times
      (down to 0.25 s), which is very promising for Raman spectroscopy of
      microbiological cells.

PMID- 25607000
TI  - Single freeform surface imaging design with unconstrained object to image
      mapping.
AB  - An imaging design approach which is free of third-order astigmatism for one
      freeform optical surface and the image is presented in this paper. A set of
      differential equations is derived from generalized ray tracing. The solution of
      the above derived equations provides the anastigmatic freeform optical surface,
      the image surface and the object to image mapping. The obtained design can be
      used as a good starting point for optimization. As an example, a reflective
      freeform surface is designed for a single reflective Head Mounted Display (HMD).
      This example has a 3 mm pupil, 15mm eye clearance, 24-degree diagonal full field
      of view, and the final design yields an average MTF of 62.6% across 17 field
      points.

PMID- 25607001
TI  - Asymmetric transmission of radially polarized THz radiation through a double
      circular grating.
AB  - We report on unidirectional and asymmetric transmission of radially polarized THz
      radiation through a dual circular metallic grating with sub-wavelength slits.
      Unidirectional transmission is shown theoretically for a super-Gaussian incident
      beam, and an asymmetric transmission is demonstrated experimentally, when the
      radially polarized beam of 0.1 THz is obtained by converting a linearly polarized
      beam with a discontinuous phase retarder and a tapered waveguide. The dual
      grating does not include nonlinear materials, its operation is reciprocal, and
      analogous to that of some planar metallic gratings.

PMID- 25607002
TI  - Phase derivative method for reconstruction of slightly off-axis digital
      holograms.
AB  - A phase derivative (PD) method is proposed for reconstruction of off-axis
      holograms. In this method, a phase distribution of the tested object wave
      constrained within 0 to pi radian is firstly worked out by a simple analytical
      formula; then it is corrected to its right range from -pi to pi according to the
      sign characteristics of its first-order derivative. A theoretical analysis
      indicates that this PD method is particularly suitable for reconstruction of
      slightly off-axis holograms because it only requires the spatial frequency of the
      reference beam larger than spatial frequency of the tested object wave in
      principle. In addition, because the PD method belongs to a pure local method with
      no need of any integral operation or phase shifting algorithm in process of the
      phase retrieval, it could have some advantages in reducing computer load and
      memory requirements to the image processing system. Some experimental results are
      given to demonstrate the feasibility of the method.

PMID- 25607003
TI  - Enhanced coherence between condensates formed resonantly at different times.
AB  - We demonstrate coherence between exciton-polariton condensates created resonantly
      at different times. The coherence persists much longer than the individual
      particle dephasing time, and this persistence increases as the particle density
      increases. The observed coherence time exceeds that of the injecting laser pulse
      by more than an order of magnitude. We show that this significant coherence
      enhancement relies critically on the many-body particle interactions, as verified
      by its dependence on particle density, interaction strength, and bath
      temperature, whereas the mass of the particles plays no role in the condensation
      of resonantly injected polaritons. Furthermore, we observe a large nonlinear
      phase shift resulting from intra-condensate interaction energy. Our results
      provide a new approach for probing ultrafast dynamics of resonantly-created
      condensates and open new directions in the study of coherence in matter.

PMID- 25607004
TI  - Novel glucose sensor based on enzyme-immobilized 81 degrees  tilted fiber
      grating.
AB  - We demonstrate a novel glucose sensor based on an optical fiber grating with an
      excessively tilted index fringe structure and its surface modified by glucose
      oxidase (GOD). The aminopropyltriethoxysilane (APTES) was utilized as binding
      site for the subsequent GOD immobilization. Confocal microscopy and fluorescence
      microscope were used to provide the assessment of the effectiveness in modifying
      the fiber surface. The resonance wavelength of the sensor exhibited red-shift
      after the binding of the APTES and GOD to the fiber surface and also in the
      glucose detection process. The red-shift of the resonance wavelength showed a
      good linear response to the glucose concentration with a sensitivity of 0.298
      nm.(mg/ml)-1 in the very low concentration range of 0.0~3.0mg/ml. Compared to the
      previously reported glucose sensor based on the GOD-immobilized long period
      grating (LPG), the 81 degrees  tilted fiber grating (81 degrees -TFG) based
      sensor has shown a lower thermal cross-talk effect, better linearity and higher Q
      factor in sensing response. In addition, its sensitivity for glucose
      concentration can be further improved by increasing the grating length and/or
      choosing a higher-order cladding mode for detection. Potentially, the proposed
      techniques based on 81 degrees -TFG can be developed as sensitive, label free and
      micro-structural sensors for applications in food safety, disease diagnosis,
      clinical analysis and environmental monitoring.

PMID- 25607005
TI  - Phase noise tolerance study in coherent optical circular QAM transmissions with
      Viterbi-Viterbi carrier phase estimation.
AB  - We present a performance evaluation of a non-conventional approach to implement
      phase noise tolerant optical systems with multilevel modulation formats. The
      performance of normalized Viterbi-Viterbi carrier phase estimation (V-V CPE) is
      investigated in detail for circular m-level quadrature amplitude modulation (C
      mQAM) signals. The intrinsic property of C-mQAM constellation points with a
      uniform phase separation allows a straightforward employment of V-V CPE without
      the need to adapt constellation. Compared with conventional feed-forward CPE for
      square QAM signals, the simulated results show an enhanced tolerance of linewidth
      symbol duration product (DeltanuTs) at a low sensitivity penalty by using feed
      forward CPE structure with C-mQAM. This scheme can be easily upgraded to higher
      order modulations without inducing considerable complexity.

PMID- 25607006
TI  - Elimination of image flicker in fringe-field switching liquid crystal display
      driven with low frequency electric field.
AB  - Recently, a low frequency driving of a fringe-field switching-liquid crystal
      display (FFS-LCD) draws much attention to minimize the power consumption. In the
      low frequency driving of FFS-LCD, an image flickering effect occurs when the sign
      of the electric field is reversed. We suggested a method to eliminate the image
      flickering effect by doping small amount of bent-core liquid crystal (BLC)
      molecules. The BLC molecules have an opposite sign of flexoelectric polarization
      and reduce the flexoelectric polarization of the host liquid crystal. By adding
      2.0 wt% of BLC, the total transmittance during a positive and a negative electric
      field could be balanced and the image flickering effect was not observed by eyes.

PMID- 25607007
TI  - Effects of surface plasmon polariton-mediated interactions on second harmonic
      generation from assemblies of pyramidal metallic nano-cavities.
AB  - We use polarization-resolved two-photon microscopy to investigate second harmonic
      generation (SHG) from individual assemblies of site-controlled nano-pyramidal
      recess templates covered with silver films. We demonstrate the effect of the
      surface plasmon polaritons (SPPs) at fundamental and second-harmonic frequencies
      on the effective second order susceptibility tensor as a function of pyramid
      arrangement and inter-pyramid distance. These results open new perspectives for
      the application of SHG microscopy as a sensitive probe of coherently excited
      SPPs, as well as for the design of new plasmonic nanostructure assemblies with
      tailored nonlinear optical properties. 

PMID- 25607008
TI  - High efficiency germanium-assisted grating coupler.
AB  - We propose a fiber to submicron silicon waveguide vertical coupler utilizing
      germanium-on-silicon gratings. The germanium is epitaxially grown on silicon in
      the same step for building photodetectors. Coupling efficiency based on FDTD
      simulation is 76% at 1.55 um and the optical 1dB bandwidth is 40 nm. 

PMID- 25607009
TI  - Self-reconstructing spatiotemporal light bullets.
AB  - We show that spatiotemporal light bullets generated by self-focusing and
      filamentation of 100 fs, 1.8 MUm pulses in a dielectric medium with anomalous
      group velocity dispersion (sapphire) are extremely robust to external
      perturbations. We present the experimental results supported by the numerical
      simulations that demonstrate complete spatiotemporal self-reconstruction of the
      light bullet after hitting an obstacle, which blocks its intense core carrying
      the self-compressed pulse, in nonlinear as well as in linear (free-space)
      propagation regimes.

PMID- 25607010
TI  - Wavefront correction in the extreme ultraviolet wavelength range using
      piezoelectric thin films.
AB  - A new scheme for wavefront correction in the extreme ultraviolet wavelength range
      is presented. The central feature of the scheme is the successful growth of
      crystalline piezoelectric thin films with the desired orientation on an amorphous
      glass substrate. The piezoelectric films show a high piezoelectric coefficient of
      250 pm/V. Using wavefront calculations we show that the grown films would enable
      high-quality wavefront correction, based on a stroke of 25 nm, with voltages that
      are well below the electrical breakdown limit of the piezoelectric film. 

PMID- 25607011
TI  - Electronic and optical properties of quaternary alloy GaAsBiN lattice-matched to
      GaAs.
AB  - Employing first-principles combined with hybrid functional calculations, the
      electronic and optical properties of GaAs alloyed with isovalent impurities Bi
      and N are investigated. As GaAsBiN alloy is a quaternary alloy, the band gap and
      the lattice constant of the alloy can be individually tuned. Both impurities are
      important to the valence band and conduction band of the alloy, with the band gap
      of the alloy being dramatically reduced by Bi 6p states and N localized 2s
      states. Interestingly, the calculated optical properties of the quaternary alloy
      are similar to those of undoped GaAs except that the absorption edge has a
      redshift toward lower energy. These results suggest potential interest in the
      long-wavelength applications of GaAsBiN alloy. 

PMID- 25607012
TI  - Improve spatial resolution by Modeling Finite Focal Spot (MFFS) for industrial CT
      reconstruction.
AB  - The finite focal spot is one of the major limitations of the high spatial
      resolution CT, especially to the high-energy industrial CT system with a macro
      focus x-ray source. In this paper, we propose an efficient reconstruction
      framework through finite focal spot size based projection modeling to improve the
      spatial resolution of current industrial CT system, and demonstrate the superior
      performance of this method. First of all, the blurred projection produced by a
      finite size source is modeled as the integral ideal projection of a given point
      source over the finite focal spot support. Under the model discretization, the
      approximate linear equivalence relation between the actual finite focus model and
      the ideal point source model is established. Then a projection recovery method
      with this relationship is presented to recover the projection of the finer focal
      spot from the blurred projection. Finally, a high-spatial resolution image can be
      reconstructed from the recovered projections using the standard Filtered Back
      Projection (FBP) algorithm. Furthermore the noise in the reconstructed image with
      different model parameters is studied and a difference image based fusion method
      is presented for the further suppression of the noise caused by the projection
      analysis processing. Both numerical simulations and real experiments have shown
      that the proposed reconstruction framework with the outstanding performance and
      efficiency characteristics can significantly enhance the spatial resolutions of
      current high-energy industrial CT systems. 

PMID- 25607013
TI  - Diode-pumped, actively Q-switched Nd:YAG laser with self-adaptive, reciprocal,
      closed-loop resonator.
AB  - We demonstrate, for the first time to our knowledge, active Q-switching in self
      adaptive, reciprocal, closed-loop, diode-side-pumped Nd:YAG slab laser. Pulse
      energy of 19 mJ with 9.5 ns pulse duration, corresponding to 2 MW of peak power
      with near-diffraction-limited beam quality was achieved. 

PMID- 25607014
TI  - Nematicons in planar cells subject to the optical Freedericksz threshold.
AB  - We investigate, both theoretically and experimentally, self-trapping of light
      beams in nematic liquid crystals arranged so as to exhibit the optical
      Freedericksz transition in planar cells. The resulting threshold in the nonlinear
      reorientational response supports a bistable behavior between diffracting and
      self-localized beam states, leading to the appearance of a hysteretic loop versus
      input excitation. Our results confirm the role of nematic liquid crystals in the
      study of non-perturbative nonlinear photonics. 

PMID- 25607015
TI  - Optical nano-structuring in light-sensitive AgCl-Ag waveguide thin films:
      wavelength effect.
AB  - Irradiation of photosensitive thin films results in the nanostructures formation
      in the interaction area. Here, we investigate how the formation of nanostructures
      in photosensitive waveguide AgCl thin films, doped by Ag nanoparticles, can be
      customized by tuning the wavelength of the incident beam. We found, silver
      nanoparticles are pushed towards the interference pattern minima created by the
      interference of the incident beam with the excited TE<sub>n</sub>-modes of the
      AgCl-Ag waveguide. The interference pattern determines the grating constant of
      the resulting spontaneous periodic nanostructures. Also, our studies indicate a
      strong dependence of the shape and size distribution of the formed Ag nano
      coalescences on the wavelength of the incident beam. It also influences on the
      surface coverage of the sample by the formed silver nanoparticles and on period
      of the self-organized nano-gratings. It is found, exposure time and intensity of
      the incident light are the most determinant parameters for the quality and
      finesse of our nanostructures. More intense incident light with shorter exposure
      time generates more regular nanostructures with smaller nano-coalescences and,
      produces gratings with higher diffraction efficiency. At constant intensity
      longer exposure time produces more complete nanostructures because of optical
      positive feedback. We observed exposure with longer wavelength produces finer
      gratings. 

PMID- 25607016
TI  - Interferometric measurement of the temperature coefficient of the refractive
      index dn/dT and the coefficient of thermal expansion of Pr:YLF laser crystals.
AB  - We report interferometric measurements of the temperature coefficient of the
      refractive index (dn/dT) and the coefficient of thermal expansion (alpha) of a
      praseodymium-doped yttrium lithium fluoride (Pr:YLF) crystal and of a fused
      silica reference sample. Our phase-resolved interferometric method yields a large
      number of data points and thus allows a precise measurement and a good error
      estimation. Furthermore, both dn/dT and alpha are obtained simultaneously from a
      single measurement which reduces errors that can occur in separate measurements.
      Over the temperature range from 20  degrees C to 80  degrees C, the value of
      dn/dT of Pr:YLF decreases from -5.2 * 10(-6)/K to -6.2 * 10(-6)/K for the
      ordinary refractive index and from -7.6 * 10(-6)/K to -8.6 * 10(-6)/K for the
      extraordinary refractive index. The coefficient of thermal expansion for the a
      axis of Pr:YLF increases from 16.4 * 10(-6)/K to 17.8 * 10(-6)/K over the same
      temperature range.

PMID- 25607017
TI  - Purely lossy and robust quantum interfaces between light and matter.
AB  - The commonly used teleportation-based interfaces between light and matter are
      very sensitive to noise of matter systems and also to the optical in-coupling and
      out-coupling losses. These imperfections produce classical noise in the
      teleportation interface, which significantly limits the transmission of quantum
      states. We propose robust quantum interfaces between weakly coupled continuous
      variables of light and matter. The state transfer introduces only pure loss,
      without any additional classical noise, despite a presence of in-coupling and out
      coupling optical losses. These interfaces qualitatively overcome commonly used
      interfaces based on quantum teleportation. 

PMID- 25607018
TI  - Low-voltage-tunable nanobeam lasers immersed in liquid crystals.
AB  - A low-voltage-tunable one-dimensional nanobeam laser is realized by employing
      lithographically defined lateral electrodes. An InGaAsP nanobeam with a sub
      micrometer width is transfer-printed in the middle of two electrodes using a
      polydimethylsiloxane stamp. Spectral tuning is achieved by controlling the
      molecular alignment of the surrounding liquid crystals (LCs). From MUm-scale-gap
      structures, a total wavelength shift that exceed 6 nm is observed at a low
      voltage of less than 10 V. A measured spectral tuning rate of 0.87 nm/V, which is
      the largest value ever reported to our knowledge among LC-tuned photonic crystal
      lasers, was also noted. 

PMID- 25607019
TI  - Color-filter-free spatial visible light communication using RGB-LED and mobile
      phone camera.
AB  - A novel color-filter-free visible-light communication (VLC) system using red
      green-blue (RGB) light emitting diode (LED) and mobile-phone camera is proposed
      and demonstrated for the first time. A feature matching method, which is based on
      the scale-invariant feature transform (SIFT) algorithm for the received grayscale
      image is used instead of the chromatic information decoding method. The proposed
      method is simple and saves the computation complexity. The signal processing is
      based on the grayscale image computation; hence neither color-filter nor
      chromatic channel information is required. A proof-of-concept experiment is
      performed and high performance channel recognition is achieved. 

PMID- 25607020
TI  - Wired and wireless convergent extended-reach optical access network using direct
      detection of all-optical OFDM super-channel signal.
AB  - We propose and demonstrate the feasibility of using all-optical orthogonal
      frequency division multiplexing (AO-OFDM) for the convergent optical wired and
      wireless access networks. AO-OFDM relies on all-optically generated orthogonal
      subcarriers; hence, high data rate (> 100 Gb/s) can be easily achieved without
      hitting the speed limit of electronic digital-to-analog and analog-to-digital
      converters (DAC/ADC). A proof-of-concept convergent access network using AO-OFDM
      super-channel (SC) is demonstrated supporting 40 - 100 Gb/s wired and gigabit/s
      100 GHz millimeter-wave (MMW) ROF transmissions. 

PMID- 25607021
TI  - Effects of exchange correlation functional on optical permittivity of gold and
      electromagnetic responses.
AB  - Understanding the optical properties of nanometer-scale noble metals is important
      for the nanoplasmonic devices. The bulk gold and thin film are calculated by
      density functional theory (DFT) with LDA, PBE, and GLLBSC functionals,
      respectively. The GLLBSC results for bulk gold are closer to the experimental
      data because the GLLBSC functional has better descriptions of transition energy.
      The Im(epsilon) of thin film calculated by LDA and PBE are overestimated. The
      effects of DFT-based optical properties are performed by conducting
      electromagnetic simulations. The transmission for the gold thin film by GLLBSC is
      blue-shifted. The gold grating structure with the GLLBSC-based optical
      permittivity has strong localized streamlines of Poynting vector in the corner
      edges at the resonance condition.

PMID- 25607022
TI  - Germanium as a material for stimulated Brillouin scattering in the mid-infrared.
AB  - In a theoretical design study, we propose buried waveguides made of germanium or
      alloys of germanium and other group-IV elements as a CMOS-compatible platform for
      robust, high-gain stimulated Brillouin scattering (SBS) applications in the mid
      infrared regime. To this end, we present numerical calculations for backward-SBS
      at 4 MUm in germanium waveguides that are buried in silicon nitride. Due to the
      strong photoelastic anisotropy of germanium, we investigate two different
      orientations of the germanium crystal with respect to the waveguide's propagation
      direction and find considerable differences. The acoustic wave equation is solved
      including crystal anisotropy; acoustic losses are computed from the acoustic mode
      patterns and previously published material parameters. 

PMID- 25607023
TI  - Size effects on metal-insulator phase transition in individual vanadium dioxide
      nanowires.
AB  - We report the size effects on the metal-insulator phase transition of vanadium
      dioxide (VO2) nanowires prepared by chemical vapor deposition. The phase
      transition temperature can be tuned from 67  degrees C in the bulk VO2 to as low
      as 29 degrees C by reducing the diameter of VO2 nanowires to nanoscale.
      Temperature-dependent Raman spectra display a clear dynamic picture on the metal
      insulator phase transition process of the VO2 nanowires. Whilst, Raman study
      shows no remarkable strain effect on the phase transition behaviors of our
      samples. The increasing surface defect density with reducing nanowire size
      facilitates the decreasing phase transition temperature. In addition, the
      polarized-photocurrent effect was observed, resulting from the anisotropy of the
      photoresponse and also caused by the reduced dimensionality.Our results indicate
      that size of VO2 nanostructures can dominate their thermoelectric and
      photoelectrical properties.

PMID- 25607024
TI  - 3D simulation of the image formation in soft x-ray microscopes.
AB  - In water-window soft x-ray microscopy the studied object is typically larger than
      the depth of focus and the sample illumination is often partially coherent. This
      blurs out-of-focus features and may introduce considerable fringing.
      Understanding the influence of these phenomena on the image formation is
      therefore important when interpreting experimental data. Here we present a wave
      propagation model operating in 3D for simulating the image formation of thick
      objects in partially coherent soft x-ray microscopes. The model is compared with
      present simulation methods as well as with experiments. The results show that our
      model predicts the image formation of transmission soft x-ray microscopes more
      accurately than previous models. 

PMID- 25607025
TI  - Splitting after collision of high-order bright spatial solitons in Kerr media.
AB  - By numerically studying the collision between (1 + 1)-Dimensional high order
      bright spatial solitons in a Kerr nonlinear media we show that after the
      collision, the high order solitons split into a number of first order solitons
      that corresponds to its order. Two different collision scenarios are considered:
      collision between two independent high order solitons and a collision with a
      virtual soliton simulated by the reflection at an angle of a high order soliton
      at a linear interface. The results demonstrate that in both cases the high order
      solitons split showing minor differences.

PMID- 25607026
TI  - Three-photon excitation source at 1250 nm generated in a dual zero dispersion
      wavelength nonlinear fiber.
AB  - We demonstrate 1250 nm pulses generated in dual-zero dispersion photonic crystal
      fiber capable of three-photon excitation fluorescence microscopy. The total power
      conversion efficiency from the 28 fs seed pulse centered at 1075 nm to pulses at
      1250 nm, including coupling losses from the nonlinear fiber, is 35%, with up to
      67% power conversion efficiency of the fiber coupled light. Frequency-resolved
      optical gating measurements characterize 1250 nm pulses at 0.6 nJ and 2 nJ,
      illustrating the change in nonlinear spectral phase accumulation with pulse
      energy even for nonlinear fiber lengths < 50 mm. The 0.6 nJ pulse has a 26 fs
      duration and is the shortest nonlinear fiber derived 1250 nm pulse yet reported
      (to the best of our knowledge). The short pulse durations and energies make these
      pulses a viable route to producing light at 1250 nm for multiphoton microscopy,
      which we we demonstrate here, via a three-photon excitation fluorescence
      microscope. 

PMID- 25607027
TI  - Radiation hardness of high-Q silicon nitride microresonators for space compatible
      integrated optics.
AB  - Integrated optics has distinct advantages for applications in space because it
      integrates many elements onto a monolithic, robust chip. As the development of
      different building blocks for integrated optics advances, it is of interest to
      answer the important question of their resistance with respect to ionizing
      radiation. Here we investigate effects of proton radiation on high-Q (theta(106))
      silicon nitride microresonators formed by a waveguide ring. We show that the
      irradiation with high-energy protons has no lasting effect on the linear optical
      losses of the microresonators.

PMID- 25607028
TI  - Identifying modes of large whispering-gallery mode resonators from the spectrum
      and emission pattern.
AB  - Identifying the mode numbers in whispering-gallery mode resonators (WGMRs) is
      important for tailoring them to experimental needs. Here we report on a novel
      experimental mode analysis technique based on the combination of frequency
      analysis and far-field imaging for high mode numbers of large WGMRs. The radial
      mode numbers q and the angular mode numbers p = l-m are identified and labeled
      via far-field imaging. The polar mode numbers l are determined unambiguously by
      fitting the frequency differences between individual whispering gallery modes
      (WGMs). This allows for the accurate determination of the geometry and the
      refractive index at different temperatures of the WGMR. For future applications
      in classical and quantum optics, this mode analysis enables one to control the
      narrow-band phase-matching conditions in nonlinear processes such as second
      harmonic generation or parametric down-conversion.

PMID- 25607029
TI  - Metal-insulator-metal plasmonic absorbers: influence of lattice.
AB  - We experimentally demonstrate three kinds of metal-insulator-metal based
      plasmonic absorbers consisting of arrays of gold nanodisks distributed in
      different lattices, including square, triangular and honeycomb lattices. It's
      found that resonances originated from localized surface plasmon undergo little
      changes with respect to different lattice distributions of the nanodisks. The
      interparticle coupling results in a minor bandwidth broadening of the fundamental
      mode. Different from square- and triangular-lattice absorbers, honeycomb-lattice
      absorber possesses a unique red-shifting (with respect to incident angles) narrow
      band high-order mode, which originates from coupling of incident light to
      propagating surface plasmon polariton (SPP) waves. Similar high-order mode can
      also be generated in square-lattice absorber by increasing the period so that a
      smaller reciprocal lattice vector can be introduced to excite the SPP mode.
      Furthermore, we show that two types of resonances can interact and create Fano
      type resonances. The simulation results agree well with the experimental results.

PMID- 25607030
TI  - Quantum control study of ultrafast optical responses in semiconductor quantum dot
      devices.
AB  - Two quantum control spectroscopic techniques were applied to study InAs quantum
      dot (QD) devices, which contain different strain-reducing layers. By adaptively
      control light matter interaction, a delayed resonant response from the InAs QDs
      was found to be encoded into the optimal phase profile of ultrafast optical pulse
      used. We verified the delayed resonant response to originate from excitons
      coupled to acoustic phonons of InAs QDs with two-dimensional coherent
      spectroscopy. Our study yields valuable dynamical information that can deepen our
      understanding of the coherent coupling process of exciton in the quantum-confined
      systems. 

PMID- 25607031
TI  - Optical Kerr nonlinearity in a high-Q silicon carbide microresonator.
AB  - We demonstrate a high-Q amorphous silicon carbide (a-SiC) microresonator with
      optical Q as high as 1.3 * 10(5). The high optical quality allows us to
      characterize the third-order nonlinear susceptibility of a-SiC. The Kerr
      nonlinearity is measured to be n2 = (5.9 +/- 0.7) * 10(-15) cm(2)/W in the
      telecom band around 1550 nm. The strong Kerr nonlinearity and high optical
      quality render a-SiC microresonators a promising platform for integrated
      nonlinear photonics.

PMID- 25607032
TI  - Unusual electromagnetic scattering by cylinders of topological insulator.
AB  - Topological insulators (TIs) show unusual optical responses resulting from a
      topological magnetoelectric (TME) effect. In this paper, we study theoretically
      the scattering of electromagnetic waves by circular TI cylinders. In certain
      configurations, the bulk scattering can be suppressed, leading to strong
      scattering in the backward direction in both Rayleigh and Mie scattering regimes
      due to the TME effect. At antiresonances, an interesting filed trapping
      phenomenon is found which is absent in conventional dielectric cylinders. 

PMID- 25607033
TI  - Efficient band-pass color filters enabled by resonant modes and plasmons near the
      Rayleigh anomaly.
AB  - We design and fabricate efficient, narrow-band, transmission color filters whose
      operating principle resides in a narrow-band guided-mode resonance associated
      with a surface-plasmon resonance. The fundamental device consists of an aluminum
      grating over a 200-nm-thick aluminum oxide film on a glass substrate. Numerical
      simulations show a sharp resonance-derived spectral profile that is additionally
      shaped by a neighboring Rayleigh anomaly. Besides the Rayleigh effect, we show
      numerically that the narrow bandwidth is predominantly due to the low refractive
      index contrast between the waveguide film and the substrate. Red, green, and blue
      filters are fabricated using ultraviolet holographic lithography followed by a
      lift-off process. The experimental spectral efficiency in transmission exceeds
      80% with full-width-at-half-maximum linewidths near 20 nm. We provide color
      images of the zero-order transmitted spectra, and illustrate the pure colors
      associated with the modal resonance extracted as side-coupled output light. 

PMID- 25607034
TI  - STED-SPIM made simple.
AB  - We report the development of a stimulated emission depletion (STED) selective
      plane illumination (SPIM) microscope based on a single diode-pumped solid state
      (DPSS) laser that simultaneously delivers nanosecond-pulses at two wavelengths.
      The two wavelengths, 355 nm and 532 nm, are generated by harmonic conversion and
      they are used to induce respectively excitation and stimulated emission
      depletion. This source should allow a low-cost, compact, very efficient and
      simplified STED scheme since the two beams are intrinsically aligned and
      synchronized. Using a chromatic beam shaping device which leaves the excitation
      beam unaffected and produces a donut-shaped STED beam, we demonstrate a 300%
      reduction of the light sheet thickness, together with an enhancement of the sheet
      uniformity over larger field of view, at low STED power, in Coumarin dye
      solution. 

PMID- 25607035
TI  - Synchronized dual tunable wavelength Q-switched Nd:Glass laser.
AB  - A flash-lamp pumped electro-optically Q-switched dual tunable wavelength Nd:Glass
      laser is demonstrated. An Nd:Glass rod was selected as the laser medium and a
      DKDP crystal was employed as the Q-switch. A cubic polarizer was placed in the
      cavity to divide the randomly polarized radiation into two orthogonally polarized
      beams. The two beams were tuned by two Littman-gratings and output independently.
      For Q-switched operation, the tuning range was 1050.1 - 1061.6 nm and 1050.5 -
      1060.2 nm for the horizontal and vertical polarizations, respectively. When the
      horizontally polarized output was fixed at 1059.1 nm, the synchronized vertically
      polarized one can be tuned from 1051.5 to 1057.5 nm. 

PMID- 25607036
TI  - Effect of metal coating in all-fiber acousto-optic tunable filter using torsional
      wave.
AB  - Torsional mode acousto-optic tunable filter (AOTF) is demonstrated using a metal
      coated birefringent optical fiber for an improved robustness. The changes in
      acoustic and optical properties of a metal-coated birefringent optical fiber
      induced by the thin metal coating were analyzed experimentally and theoretically.
      The filter wavelength shift is successfully explained as a result of combined
      effect of acoustic wavelength change and optical birefringence change. We also
      demonstrated a small form-factor configuration by coiling the fiber with 6 cm
      diameter without performance degradation. The center wavelength of the filter can
      be tuned >35 nm by changing the applied frequency, and the coupling efficiency is
      higher than 92% with <5 nm 3-dB bandwidth. 

PMID- 25607037
TI  - Enhancement of electro-optical properties of twisted nematic liquid crystals by
      doping aromatic hydrocarbon liquids.
AB  - In this paper, doping liquid materials to enhance the electro-optical (EO)
      properties of twisted nematic liquid crystals (NLCs) was presented. Two aromatic
      hydrocarbon (AH) liquids, toluene and 1-methylnaphthalene, were chosen as dopants
      in order to lower the driving voltage and response time of the NLCs. A 18%
      decrease in driving voltage and response time was achieved by doping 10 wt%
      toluene into NLCs. The main reason of this phenomenon is due to a large amount of
      reduction in the rotational viscosity of AH liquids doped NLCs. This method
      provides an easy and potential choice for applications in various LC display
      systems. 

PMID- 25607038
TI  - Strong field enhancement and light-matter interactions with all-dielectric
      metamaterials based on split bar resonators.
AB  - Strong subwavelength field enhancement has often been assumed to be unique to
      plasmonic nanostructures. Here we propose a type of all-dielectric metamaterials
      based on split bar resonators. The nano gap at the centre of the resonant
      elements results in large local field enhancement and light localization in the
      surrounding medium, which can be employed for strong light-matter interactions.
      In a Fano-resonant dielectric metamaterial comprising pairs of asymmetric split
      silicon bars, the enhancement of electric field amplitude in the gap exceeds 120
      while the averaged electromagnetic energy density is enhanced by more than 7000
      times. An optical refractive index sensor with a potential sensitivity of 525
      nm/RIU is designed based on the proposed metamaterials. The proposed concept can
      be applied to other types of dielectric nanostructures and may stimulate further
      research of dielectric metamaterials for applications ranging from nonlinear
      optics and sensing to the realization of new types of active lasing devices. 

PMID- 25607039
TI  - Linearization of phase-modulated analog optical links using a four-wave mixing
      comb source.
AB  - We present a novel method for distortion elimination in phase-modulated analog
      optical links. A small part of the phase modulated signal seeds a four-wave
      mixing comb source, which generates lightwaves with integer multiples of the
      phase modulation of the original signal. These lightwaves are scaled and re
      combined with the original phase-modulated signal to cancel the distortion
      generated in the interferometric phase-to-amplitude conversion process.
      Experimentally, we demonstrate full cancelation of the third-order distortion of
      the receiver and achieve a 19-dB improvement in the link's SFDR at a 1-Hz
      bandwidth. This approach is readily extendable to eliminate all relevant higher
      order distortion products or synthesize arbitrary phase-to-amplitude transfer
      functions.

PMID- 25607040
TI  - Single-wavelength phase retrieval method from simultaneous multi-wavelength in
      line phase-shifting interferograms.
AB  - From a sequence of simultaneous multi-wavelength phase-shifting interferograms
      (SMWPSIs), a novel single-wavelength phase retrieval method based on the least
      squares iterative algorithm is proposed and utilized in dual-wavelength
      interferometry. Firstly, only one time phase-shifting procedure implements the
      phase shifts of all illumination wavelengths simultaneously, and then the
      accurate wrapped phases of each single-wavelength can be respectively retrieved
      from SMWPSIs by the least-squares iterative operation, so the phase of synthetic
      wavelength can be obtained by the subtraction easily. Using the proposed method,
      both the simulation and the experimental results demonstrate that the optical
      setup is simpler; the requirements for the displacement of the phase-shifting
      device and the number of the captured interferograms are smaller compared to the
      traditional phase-shifting multi-wavelength interferometry or off-axis multi
      wavelength interferometry. Even in the case that the phase-shifts are unknown,
      the wrapped phases and the phase-shifts of each single-wavelength can be obtained
      by the proposed method. 

PMID- 25607041
TI  - Integrated high quality factor lithium niobate microdisk resonators.
AB  - Lithium Niobate (LN) is an important nonlinear optical material. Here we
      demonstrate LN microdisk resonators that feature optical quality factor ~10(5),
      realized using robust and scalable fabrication techniques, that operate over a
      wide wavelength range spanning visible and near infrared. Using our resonators,
      and leveraging LN's large second order optical nonlinearity, we demonstrate on
      chip second harmonic generation with a conversion efficiency of 0.109 W(-1).

PMID- 25607042
TI  - High-Q MgF2 whispering gallery mode resonators for refractometric sensing in
      aqueous environment.
AB  - We present our experiments on refractometric sensing with ultrahigh-Q,
      crystalline, birefringent magnesium fluoride (MgF2) whispering gallery mode
      resonators. The difference to fused silica which is most commonly used for
      sensing experiments is the small refractive index of MgF2 which is very close to
      that of water. Compared to fused silica this leads to more than 50% longer
      evanescent fields and a 4.25 times larger sensitivity. Moreover the birefringence
      amplifies the sensitivity difference between TM and TE type modes which will
      enhance sensing experiments based on difference frequency measurements. We
      estimate the performance of our resonators and compare them with fused silica
      theoretically and present experimental data showing the interferometrically
      measured evanescent field decay and the sensitivity of mm-sized MgF2 whispering
      gallery mode resonators immersed in water. These data show reasonable agreement
      with the developed theory. Furthermore, we observe stable Q factors in water well
      above 1 * 108.

PMID- 25607043
TI  - Effects of inhomogeneities and drift on the dynamics of temporal solitons in
      fiber cavities and microresonators.
AB  - In [Phys. Rev. Lett. 110, 064103 (2013)], using the Swift-Hohenberg equation, we
      introduced a mechanism that allows to generate oscillatory and excitable soliton
      dynamics. This mechanism was based on a competition between a pinning force at
      inhomogeneities and a pulling force due to drift. Here, we study the effect of
      such inhomogeneities and drift on temporal solitons and Kerr frequency combs in
      fiber cavities and microresonators, described by the Lugiato-Lefever equation
      with periodic boundary conditions. We demonstrate that for low values of the
      frequency detuning the competition between inhomogeneities and drift leads to
      similar dynamics at the defect location, confirming the generality of the
      mechanism. The intrinsic periodic nature of ring cavities and microresonators
      introduces, however, some interesting differences in the final global states. For
      higher values of the detuning we observe that the dynamics is no longer described
      by the same mechanism and it is considerably more complex. 

PMID- 25607044
TI  - Multiphoton microscopy as a detection tool for photobleaching of EO materials.
AB  - Multi-photon microscopy operating at 1550 nm is employed as a rapid
      characterization tool for studying the photostability of three well-known electro
      optical materials. Different nonlinear optical responses such as multi-photon
      excitation fluoresence, second-, and third-harmonic generation can be used as
      detection probes to reveal the degradation mechanisms. This technique is rapid,
      accurate, and can be used to study the photostability of a broad range of
      materials. 

PMID- 25607045
TI  - Energy band structure tailoring of vertically aligned InAs/GaAsSb quantum dot
      structure for intermediate-band solar cell application by thermal annealing
      process.
AB  - This study presents an band-alignment tailoring of a vertically aligned
      InAs/GaAs(Sb) quantum dot (QD) structure and the extension of the carrier
      lifetime therein by rapid thermal annealing (RTA). Arrhenius analysis indicates a
      larger activation energy and thermal stability that results from the suppression
      of In-Ga intermixing and preservation of the QD heterostructure in an annealed
      vertically aligned InAs/GaAsSb QD structure. Power-dependent and time-resolved
      photoluminescence were utilized to demonstrate the extended carrier lifetime from
      4.7 to 9.4 ns and elucidate the mechanisms of the antimony aggregation resulting
      in a band-alignment tailoring from straddling to staggered gap after the RTA
      process. The significant extension in the carrier lifetime of the columnar
      InAs/GaAsSb dot structure make the great potential in improving QD intermediate
      band solar cell application. 

PMID- 25607046
TI  - Simple carrier-phase estimator for high-speed RSOA-based coherent WDM PON.
AB  - It has been recently reported that reflective semiconductor optical amplifiers
      (RSOAs) can be used as phase modulators for the cost-effective implementation of
      the high-speed wavelength-division-multiplexed passive optical networks (WDM
      PONs). For the detection of the phase-shift-keying (PSK) signal generated by
      using an RSOA, we should be able to estimate its carrier phase accurately at the
      digital coherent receiver. However, when the baud rate of this PSK signal is set
      to be much higher than the RSOA's modulation bandwidth, the conventional M-th
      power algorithm cannot estimate its carrier phase accurately. To solve this
      problem, we develop a simple carrier-phase estimation technique for the high
      speed (>10 Gb/s) PSK signals generated by using bandwidth-limited RSOAs. This
      technique estimates the carrier phase of the PSK signal by measuring the angular
      direction of the opening occurred in the trajectory of the phasor diagram. By
      using the proposed technique, we demonstrate the upstream transmission of the
      25.78-Gb/s quadrature phase-shift-keying (QPSK) signal generated by using an RSOA
      (3-dB bandwidth: 3.2 GHz) in a 60-km reach coherent WDM PON. 

PMID- 25607047
TI  - Blue electroluminescence from Sb-ZnO/Cd-ZnO/Ga-ZnO heterojunction diode
      fabricated by dual ion beam sputtering.
AB  - p-type Sb-doped ZnO/i-CdZnO/n-type Ga-doped ZnO was grown by dual ion beam
      sputtering deposition system. Current-voltage characteristics of the
      heterojunction showed a diode-like rectifying behavior with a turn-on voltage of
      ~5 V. The diode yielded blue electroluminescence emissions at around 446 nm in
      forward biased condition at room temperature. The emission intensity increased
      with the increase of the injection current. A red shifting of the emission peak
      position was observed with the increment of ambient temperature, indicating a
      change of band gap of the CdZnO active layer with temperature in low-temperature
      measurement. 

PMID- 25607048
TI  - Statistical measurements of quantum emitters coupled to Anderson-localized modes
      in disordered photonic-crystal waveguides.
AB  - We present a statistical study of the Purcell enhancement of the light emission
      from quantum dots coupled to Anderson-localized cavities formed in disordered
      photonic-crystal waveguides. We measure the time-resolved light emission from
      both single quantum emitters coupled to Anderson-localized cavities and directly
      from the cavities that are fed by multiple quantum dots. Strongly inhibited and
      enhanced decay rates are observed relative to the rate of spontaneous emission in
      a homogeneous medium. From a statistical analysis, we report an average Purcell
      factor of 4.5 +/- 0.4 without applying any spectral tuning. By spectrally tuning
      individual quantum dots into resonance with Anderson-localized modes, a maximum
      Purcell factor of 23.8 +/- 1.5 is recorded, which is at the onset of the strong
      coupling regime. Our data quantify the potential of Anderson-localized cavities
      for controlling and enhancing the light-matter interaction strength in a photonic
      crystal waveguide, which is of relevance for cavity quantum-electrodynamics
      experiments, efficient energy harvesting and random lasing.

PMID- 25607049
TI  - Experimental demonstration of selective compression of femtosecond pulses in the
      Laue scheme of the dynamical Bragg diffraction in 1D photonic crystals.
AB  - We present the experimental results of diffraction-induced temporal splitting of
      chirped femtosecond optical pulses under the dynamical Bragg diffraction in the
      Laue geometry. For the experiments we made a transparent, high quality porous
      quartz based 1D photonic crystal composed of 500 layers. We demonstrate that a
      selective compression of pulses is observed in this case, that is only one pulse
      from the pair is compressed, while the second one is broadened. This selective
      compression effect is determined by the sign and the value of the chirp parameter
      of the input pulse, in agreement with the theoretical description. 

PMID- 25607050
TI  - Gigahertz frequency comb from a diode-pumped solid-state laser.
AB  - We present the first stabilization of the frequency comb offset from a diode
      pumped gigahertz solid-state laser oscillator. No additional external
      amplification and/or compression of the output pulses is required. The laser is
      reliably modelocked using a SESAM and is based on a diode-pumped Yb:CALGO gain
      crystal. It generates 1.7-W average output power and pulse durations as short as
      64 fs at a pulse repetition rate of 1 GHz. We generate an octave-spanning
      supercontinuum in a highly nonlinear fiber and use the standard f-to-2f carrier
      envelope offset (CEO) frequency f<sub>CEO</sub> detection method. As a pump
      source, we use a reliable and cost-efficient commercial diode laser. Its multi
      spatial-mode beam profile leads to a relatively broad frequency comb offset beat
      signal, which nevertheless can be phase-locked by feedback to its current. Using
      improved electronics, we reached a feedback-loop-bandwidth of up to 300 kHz. A
      combination of digital and analog electronics is used to achieve a tight phase
      lock of f<sub>CEO</sub> to an external microwave reference with a low in-loop
      residual integrated phase-noise of 744 mrad in an integration bandwidth of [1 Hz,
      5 MHz]. An analysis of the laser noise and response functions is presented which
      gives detailed insights into the CEO stabilization of this frequency comb. 

PMID- 25607051
TI  - Thulium-doped all-fiber mode-locked laser based on NPR and 45 degrees -tilted
      fiber grating.
AB  - A nonlinear polarization rotation based all-fiber passively mode-locked Tm3+
      doped fiber laser is demonstrated by using a 45 degrees  tilted fiber grating
      (TFG) as an in-line polarizer. The 45 degrees  TFG centered at 2000 nm with
      polarization dependent loss (PDL) of >12 dB at 1850 nm~2150 nm range was UV
      inscribed for the first time in SM28 fiber using a 244 nm Ar+ continuous wave
      laser and a phase mask with 25 mm long uniform pitch and titled period pattern of
      33.7 degrees  with respect to the fiber axis. Stable soliton pulses centered at
      1992.7 nm with 2.02 nm FWHM bandwidth were produced at a repetition rate of 1.902
      MHz with pulse duration of 2.2 ps and pulse energy of 74.6 pJ. As increased pump
      power, the laser also can operate at noise-like regime with 18.1 nm FWHM
      bandwidth and pulse energy of up to 250.1 nJ. Using the same 45 degrees  TFG,
      both stable soliton and noise-like mode-locking centered at ~1970 nm and ~2050
      nm, were also achieved by shortening and extending the length of Tm3+-doped
      fiber, respectively, exhibiting advantages of broadband and low insertion loss at
      2 um band.

PMID- 25607052
TI  - Dispersion engineered Ge11.5As24 Se64.5 nanowire for supercontinuum generation: a
      parametric study.
AB  - A promising design of Ge11.5As24 Se64.5 nanowires for supercontinuum generation
      is proposed through numerical simulations. It can be used for generating a
      supercontinuum with 1300-nm bandwidth. The dispersion parameters upto eighth
      order are obtained by calculating the effective mode index with the finite
      element method. We have investigated dispersion curves for a number of nanowire
      geometries. Through dispersion engineering and by varying dimensions of the
      nanowires we have identified a promising structure that shows possibility of
      realizing a wideband supercontinuum. We have found significant variations in its
      bandwidth with the inclusion of higher-order dispersion coefficients and
      indicated the possibility of obtaining spurious results if the adequate number of
      dispersion coefficients is not considered. To confirm the accuracy of dispersion
      coefficients obtained through numerical computations, we have shown that a data
      fitting procedure based on the Taylor series expansion provides good agreement
      with the actual group velocity dispersion curve obtained by using a full
      vectorial finite-element mode-solver.

PMID- 25607053
TI  - An adaptive liquid lens with a reciprocating movement in a cylindrical hole.
AB  - We demonstrate a liquid droplet which can do a reciprocating movement in a
      cylindrical hole. The droplet in the hole exhibits a lens character. By applying
      a voltage, the border of the droplet is stretched to expand by the generated
      dielectric force. Due to the fixed volume, the dome of the droplet in the hole
      has to move toward the substrate without changing its surface profile. Therefore,
      the focal length of the droplet remains unchanged although the focal point is
      shifted. Once the voltage is removed, the droplet can return to its original
      state. The droplet with such a movement functions as an adaptive lens. Our lens
      can provide a high resolution (~114 lp/mm) whether or not it is actuated. The
      dynamic response time is reasonably fast. Integrating with a solid lens, the
      compound lens can provide a variable focal length. 

PMID- 25607054
TI  - Active pump-seed-pulse synchronization for OPCPA with sub-2-fs residual timing
      jitter.
AB  - Short-pulse-pumped optical parametric chirped pulse amplification (OPCPA)
      requires a precise temporal overlap of the interacting pulses in the nonlinear
      crystal to achieve stable performance. We present active synchronization of the
      ps-pump pulses and the broadband seed pulses used in an OPCPA system with a
      residual timing jitter below 2 fs. This unprecedented stability was achieved
      utilizing optical parametric amplification to generate the error signal,
      requiring less than 4 pJ of seed- and 10 uJ of pump-pulse-energy in the optical
      setup. The synchronization system shows excellent long-term performance and can
      be easily implemented in almost any OPCPA system. 

PMID- 25607055
TI  - 150 x 120 Gb/s unrepeatered transmission over 409.6 km of large effective area
      fiber with commercial Raman DWDM system.
AB  - 15 Tb/s unrepeatered transmission is achieved over 409.6 km (68.2 dB) of large
      effective area fiber using forward and backward distributed Raman amplification
      and a remotely-pumped erbium-doped optical amplifier. This result provides a
      record capacity-reach product of 6.14 Pb/s-km over a single fiber type. We also
      demonstrate channel growth from 10 to 150 waves within 61 nm amplification
      bandwidth. 

PMID- 25607056
TI  - Multispectral elastic scanning lidar for industrial flare research:
      characterizing the electronic subsystem and application.
AB  - This work deals with the analysis of the electronic subsystem of a
      multiwavelength elastic scanning lidar. Several calibration tests are applied to
      the Cubatao scanning lidar placed at the industrial area of Cubatao in the State
      of Sao Paulo (Brazil), in order to improve the knowledge of its performing itself
      and to design protocols for correcting lidar signal for undesirable instrumental
      effects. In particular, the trigger delay is assessed by means of zero-bin and
      bin-shift tests for analog (AN) and photo-counting (PC) signals, respectively.
      Dark current test is also performed to detect potential range-dependency that
      could affect lidar products. All tests were performed at different spatial
      resolutions. These instrumental corrections were applied to a case study of data
      acquired for characterizing the optical and microphysical properties of particles
      in an industrial flare. To that aim, a graphical method based on the space
      defined by the extinction-related Angstrom exponent versus its spectral curvature
      is used to derive the contribution of fine aerosol to extinction and the size of
      the fine aerosols in the industrial flare, therefore revealing features of the
      processes occurring inside the flame. Our study demonstrates the potential of
      this new technique for the study and measurement of industrial emissions.

PMID- 25607057
TI  - Extending single mode performance of all-solid large-mode-area single trench
      fiber.
AB  - We report a novel "single trench fiber" design for mode area scaling of the
      fundamental mode while offering effective single mode operation for a compact
      fiber laser device. This fiber design allows very high suppression of the higher
      order modes by offering high loss and power delocalization. It has the advantages
      of low cost and easy fabrication thanks to all solid fiber design, cylindrical
      symmetry, and higher refractive index of core as that of the cladding. A Yb-doped
      single trench fiber with a 40 um core diameter has been fabricated from modified
      chemical vapor deposition process in conjunction with solution-doping offering an
      effective mode area of as large as ~1,000 um(2) at 1,060 nm for the bend radius
      of 20 cm. Detailed characterizations confirm a robust single mode behavior of the
      fiber. Comparative analysis with other fiber designs shows significant
      performance enhancement of effective single mode operation suitable for fiber
      laser applications.

PMID- 25607058
TI  - Ultrafast multi-wavelength switch based on dynamics of spectrally-shifted
      solitons in a dual-core photonic crystal fiber.
AB  - Nonlinear propagation of ultrafast near infrared pulses in anomalous dispersion
      region of dual-core photonic crystal fiber was studied. Polarization tunable
      soliton-based nonlinear switching at multiple non-excitation wavelengths was
      demonstrated experimentally for fiber excitation by 100 fs pulses at 1650 nm. The
      highest-contrast switching was obtained with the fiber length of just 14 mm,
      which is significantly shorter compared to the conventional non-solitonic in
      fiber switching based on nonlinear optical loop mirror. Advanced numerical
      simulations show good agreement with the experimental results, suggesting that
      the underlying dual-core soliton fission process supports nonlinear optical
      switching and simultaneous pulse compression to few-cycle durations at the level
      of 20 fs. 

PMID- 25607059
TI  - High throughput second harmonic imaging for label-free biological applications.
AB  - Second harmonic generation (SHG) is inherently sensitive to the absence of
      spatial centrosymmetry, which can render it intrinsically sensitive to
      interfacial processes, chemical changes and electrochemical responses. Here, we
      seek to improve the imaging throughput of SHG microscopy by using a wide-field
      imaging scheme in combination with a medium-range repetition rate amplified near
      infrared femtosecond laser source and gated detection. The imaging throughput of
      this configuration is tested by measuring the optical image contrast for
      different image acquisition times of BaTiO3 nanoparticles in two different wide
      field setups and one commercial point-scanning configuration. We find that the
      second harmonic imaging throughput is improved by 2-3 orders of magnitude
      compared to point-scan imaging. Capitalizing on this result, we perform low
      fluence imaging of (parts of) living mammalian neurons in culture.

PMID- 25607060
TI  - Tunable Q-switched fiber laser based on saturable edge-state absorption in few
      layer molybdenum disulfide (MoS2).
AB  - We fabricate a few-layer molybdenum disulfide (MoS2) polymer composite saturable
      absorber by liquid-phase exfoliation, and use this to passively Q-switch an
      ytterbium-doped fiber laser, tunable from 1030 to 1070 nm. Self-starting Q
      switching generates 2.88 MUs pulses at 74 kHz repetition rate, with over 100 nJ
      pulse energy. We propose a mechanism, based on edge states within the bandgap,
      responsible for the wideband nonlinear optical absorption exhibited by our few
      layer MoS2 sample, despite operating at photon energies lower than the material
      bandgap.

PMID- 25607061
TI  - Background suppression in long-distance imaging using volume hologram filters.
AB  - We performed experiments using a volume hologram filter (VHF) coupled with a
      telephoto objective lens to detect weak distant signals masked by strong
      background noise. The VHF was able to selectively pass light originating from a
      certain distance while attenuating background noise contributions from other
      distances, resulting in a higher signal-to-noise ratio (SNR). The proposed method
      is useful in remote sensing applications such as daytime artificial satellite and
      space debris detection. 

PMID- 25607062
TI  - Two octaves mid-infrared supercontinuum generation in As2Se3 microwires.
AB  - We report the first demonstration of mid-infrared supercontinuum generation in
      As2Se3 chalcogenide microwires with the added advantage of using low energy
      pulses. The generated SC covers two octaves of bandwidth from 1.1 MUm to 4.4 MUm
      at -30 dB. This exceeds the broadest reported SC bandwidth in As2Se3 microwires
      by a factor of 3.5. The microwire geometry and pumping conditions are the key
      parameters in generating the 3.3 MUm bandwidth while using a low pump pulse
      energy of 500 pJ.

PMID- 25607063
TI  - Real-time coherent detection of phase modulated ultrashort pulses after time-to
      space conversion and spatial demultiplexing.
AB  - Phase modulated sub-picosecond pulses are converted by a time-to-space processor
      to quasi-monochromatic spatial beams that are spatially demultiplexed and
      coherently detected in real-time. The time-to-space processor, based on sum
      frequency generation (SFG), serves as a serial-to-parallel converter, reducing
      the temporal bandwidth of the ultrashort pulse to match the bandwidth of
      optoelectronic receivers. As the SFG process is phase preserving, we demonstrate
      homodyne coherent detection of phase modulated temporal pulses by mixing the
      demultiplexed SFG beam with a narrow linewidth local oscillator (LO) resulting in
      single-shot phase detection of the converted pulses at a balanced detector.
      Positively and negatively phase-modulated signal pulses are individually detected
      and LO shot noise limited operation is achieved. This demonstration of real-time
      demultiplexing followed by single-shot full-field detection of individual pulses,
      highlights the potential of time-to-space conversion for ultrahigh bit rate
      optical communications and data processing applications. 

PMID- 25607064
TI  - Electro-optical switching between polariton and cavity lasing in an InGaAs
      quantum well microcavity.
AB  - We report on the condensation of microcavity exciton polaritons under optical
      excitation in a microcavity with four embedded InGaAs quantum wells. The
      polariton laser is characterized by a distinct non-linearity in the input-output
      characteristics, which is accompanied by a drop of the emission linewidth
      indicating temporal coherence and a characteristic persisting emission blueshift
      with increased particle density. The temporal coherence of the device at
      threshold is underlined by a characteristic drop of the second order coherence
      function to a value close to 1. Furthermore an external electric field is used to
      switch between polariton regime, polariton condensate and photon lasing. 

PMID- 25607065
TI  - Fluorescence correlation spectroscopy with a doughnut-shaped excitation profile
      as a characterization tool in STED microscopy.
AB  - The resolution of stimulated emission depletion (STED) microscopes is ultimately
      limited by the quality of the doughnut-shaped illumination profile of the STED
      erase beam. We show here that in the focal plane this illumination profile is
      well approximated by an analytical expression - a difference of Gaussian
      functions, which tends towards a first order Laguerre-Gaussian profile in the
      case of a well aligned beam with a true zero-intensity central minimum. We
      further show that along the optical axis the maximum intensity profile is
      reasonably approximated by a Gaussian decay away from the focal plane. The result
      is a fully Gaussian analytical approximation of the three-dimensional point
      spread function of STED erase beams. This allows the derivation of an analytical
      form for the autocorrelation function of the fluorescence generated by
      fluorophore diffusion through the STED depletion volume. We verified this form to
      be correct by performing fluorescence correlation spectroscopy (FCS) experiments
      in solutions of the dye Alexa Fluor 532. Since the quality of the illumination
      profile is reflected in the shape of the autocorrelation function, we propose
      that fluctuation analysis can be used as a tool to assess the quality of STED
      erase beams.

PMID- 25607066
TI  - Non-data-aided and universal cycle slip detection and correction for coherent
      communication systems.
AB  - We propose a simple non-data-aided (or unsupervised) and universal cycle slip
      detection and correction (CS-DC) technique based on locating the minimum of the
      sliding average of twice estimated phase noise. The CS-DC can be appended to any
      carrier phase estimation(CPE) technique and is modulation format independent. We
      analytically derive the probability density function of the CS detection metric
      and study how the sliding window length and detection threshold affects CS
      detection performance. Simulation results reveal significant cycle slips
      reduction for various modulation formats with a residual CS probability of 2 *
      10<sup>-7</sup> for single carrier system even in unrealistic highly nonlinear
      system setups. In addition, we show that a second stage of CS-DC with a different
      sliding window length can further reduce the cycle slip probability by at least
      an order of magnitude. We also show that CS-DC is tolerant to inter-channel
      nonlinearities and residue frequency offset effects. Overall, the proposed CS-DC
      technique can be used in conjunction to other CS reduction techniques to maximize
      the ability of CS mitigation in next generation optical transceivers. 

PMID- 25607067
TI  - Semi-analytic texturing algorithm for polygon computer-generated holograms.
AB  - A texturing method for the semi-analytic polygon computer-generated hologram
      synthesis algorithm is studied. Through this, the full-potential and development
      direction of the semi-analytic polygon computer-generated holograms are discussed
      and compared to that of the conventional numerical algorithm of polygon computer
      generated hologram generation based on the fast Fourier transform and bilinear
      interpolation. The theoretical hurdle of the semi-analytic texturing algorithm is
      manifested and an approach to resolve this problen. A key mathematical
      approximation in the angular spectrum computer-generated hologram computation, as
      well as the trade-offs between texturing effects and computational efficiencies
      are analyzed through numerical simulation. In this fundamental study, theoretical
      potential of the semi-analytic polygon computer-generated hologram algorithm is
      revealed and the ultimate goal of research into the algorithm clarified. 

PMID- 25607068
TI  - Theoretical calculation on ICI reduction using digital coherent superposition of
      optical OFDM subcarrier pairs in the presence of laser phase noise.
AB  - Digital coherent superposition (DCS) of optical OFDM subcarrier pairs with
      Hermitian symmetry can reduce the inter-carrier-interference (ICI) noise resulted
      from phase noise. In this paper, we show two different implementations of DCS
      OFDM that have the same performance in the presence of laser phase noise. We
      complete the theoretical calculation on ICI reduction by using the model of pure
      Wiener phase noise. By Taylor expansion of the ICI, we show that the ICI power is
      cancelled to the second order by DCS. The fourth order term is further derived
      out and only decided by the ratio of laser linewidth to OFDM subcarrier symbol
      rate, which can greatly simplify the system design. Finally, we verify our
      theoretical calculations in simulations and use the analytical results to predict
      the system performance. DCS-OFDM is expected to be beneficial to certain optical
      fiber transmissions. 

PMID- 25607069
TI  - Calibration of a non-null test interferometer for the measurement of aspheres and
      free-form surfaces.
AB  - The measurement of aspheric and free-form surfaces in a non-null test
      configuration has the advantage that no compensation optics is required. However,
      if a surface is measured in a non-null test configuration, retrace errors are
      introduced to the measurement. We describe a method to calibrate the test space
      of an interferometer, enabling to compensate retrace errors. The method is
      effective even for strong deviations from null test configuration up to several
      100 waves, enabling the fast and flexible measurement of aspheres and free-form
      surfaces. In this paper we present the application of the method to the
      calibration of the Tilted Wave Interferometer. Furthermore, the method can be
      generalized to the calibration of other setups. 

PMID- 25607070
TI  - Super-transmission: the delivery of superoscillations through the absorbing
      resonance of a dielectric medium.
AB  - The delivery of a super-oscillatory optical signal through a medium with an
      absorbing resonance at the super-oscillation frequency is considered
      theoretically and through simulations. While a regular signal oscillating at the
      absorption resonance frequency would be completely absorbed after a few
      absorption lengths, it is found that the superoscillation undergoes quasi
      periodic revivals over optically thick distances. In particular revivals of
      extreme UV local oscillations propagating through Silica Glass over distances
      which are three orders of magnitude longer than the associated absorbing length
      are numerically demonstrated.

PMID- 25607071
TI  - Circular polarization interferometry: circularly polarized modes of cholesteric
      liquid crystals.
AB  - We describe a novel polarization interferometer which permits the determination
      of the refractive indices for circularly-polarized light. It is based on a Jamin
      Lebedeff interferometer, modified with waveplates, and permits us to
      experimentally determine the refractive indices nL and nR of the respectively
      left- and right-circularly polarized modes in a cholesteric liquid crystal.
      Whereas optical rotation measurements only determine the circular birefringence,
      i.e. the difference (nL - nR), the interferometer also permits the determination
      of their absolute values. We report refractive indices of a cholesteric liquid
      crystal in the region of selective (Bragg) reflection as a function of
      temperature. 

PMID- 25607072
TI  - Fast and accurate auto-focusing algorithm based on the combination of depth from
      focus and improved depth from defocus.
AB  - An auto-focus method for digital imaging systems is proposed that combines depth
      from focus (DFF) and improved depth from defocus (DFD). The traditional DFD
      method is improved to become more rapid, which achieves a fast initial focus. The
      defocus distance is first calculated by the improved DFD method. The result is
      then used as a search step in the searching stage of the DFF method. A dynamic
      focusing scheme is designed for the control software, which is able to eliminate
      environmental disturbances and other noises so that a fast and accurate focus can
      be achieved. An experiment is designed to verify the proposed focusing method and
      the results show that the method's efficiency is at least 3-5 times higher than
      that of the traditional DFF method. 

PMID- 25607073
TI  - Multi-wavelength Transmission-Reflection Analysis for fiber monitoring.
AB  - We propose and implement a novel approach based on multi-wavelength Transmission
      Reflection Analysis (MW-TRA) technique for monitoring lossy events (e.g.
      disconnected connectors, fiber breaks and fiber bendings) along an optical fiber
      link. By launching un-modulated continuous-wave lights carried by different
      wavelengths into the fiber and measuring their transmitted and
      reflected/backscattered optical powers, our proposed MW-TRA scheme is able to
      localize any lossy event (including both reflective and non-reflective) and to
      quantify the corresponding insertion and return losses with high accuracy. 

PMID- 25607074
TI  - High density 3D localization microscopy using sparse support recovery.
AB  - Single-molecule localization microscopy methods offer high spatial resolution,
      but they are not always suitable for live cell imaging due to limited temporal
      resolution. One strategy is to increase the density of photoactivated molecules
      present in each image, however suitable analysis algorithms for such data are
      still lacking. We present 3denseSTORM, a new algorithm for localization
      microscopy which is able to recover 2D or 3D super-resolution images from a
      sequence of diffraction limited images with high densities of photoactivated
      molecules. The algorithm is based on sparse support recovery and uses a Poisson
      noise model, which becomes critical in low-light conditions. For 3D data
      reconstruction we use the astigmatism and biplane imaging methods. We derive the
      theoretical resolution limits of the method and show examples of image
      reconstructions in simulations and in real 2D and 3D biological samples. The
      method is suitable for fast image acquisition in densely labeled samples and
      helps facilitate live cell studies with single molecule localization microscopy. 

PMID- 25607075
TI  - Dipole and quadrupole trapped modes within bi-periodic silicon particle array
      realizing three-channel refractive sensing.
AB  - In this research paper, multiple trapped modes within a bi-periodic silicon
      particle array were studied numerically both through finite difference time
      domain method and finite element method. Anti-phased electric dipole, magnetic
      dipole, and magnetic quadrupole collective resonances in the two arrays result in
      three distinct trapped modes, which interact with the corresponding "bright
      modes" generating three sharp asymmetric Fano profiles in reflection. The
      lineshapes can be easily tailored by particle radius to achieve very narrow
      linewidth, while still remains 100% modulation depth. As a three-channel
      refractive sensor, the sensitivities for three working frequencies are 155
      nm/RIU, 725 nm/RIU, and 190 nm/RIU.

PMID- 25607076
TI  - 1.55 um high speed low chirp electroabsorption modulated laser arrays based on
      SAG scheme.
AB  - We demonstrate a cost-effective 1.55 um low chirp 4 * 25 Gbit/s electroabsorption
      modulated laser (EML) array with 0.8 nm channel spacing by varying ridge width of
      the lasers and using selective area growth (SAG) integration scheme. The devices
      for all the 4 channels within the EML array show uniform threshold currents
      around 18 mA and high SMSRs over 45 dB. The output optical power of each channel
      is about 9 mW at an injection current of 100 mA. The typical chirp value of
      single EML measured by a fiber resonance method varied from 2.2 to -4 as the bias
      voltage was increased from 0 V to 2.5 V. These results show that the EML array is
      a suitable light source for 100 Gbit/s optical transmissions.

PMID- 25607077
TI  - Three-dimensional dielectric crystalline waveguide beam splitters in mid-infrared
      band by direct femtosecond laser writing.
AB  - We report on the fabrication of three-dimensional waveguide beam splitters in a
      dielectric Bi(4)Ge(3)O(12) (BGO) crystal by direct femtosecond laser writing. In
      the laser written tracks of BGO crystal, positive refractive index is induced,
      resulting in so-called Type I configuration waveguiding cores. The "multiscan"
      technique is utilized to shape cores with designed cross-sectional geometry in
      order to achieve guidance at mid-infrared wavelength of 4 MUm. The fundamental
      mode guidance along both TE and TM polarizations has been obtained in the
      waveguide structures. With this feature, we implement beam splitters from 2D to
      3D geometries, and realize 1 * 2, 1 * 3, and 1 * 4 power splitting at 4MUm.

PMID- 25607078
TI  - Measurement of mode coupling distribution along a few-mode fiber using a
      synchronous multi-channel OTDR.
AB  - We describe the nondestructive measurement of mode coupling along a few-mode
      fiber using a synchronous multi-channel optical time-domain reflectometer (OTDR).
      By installing a few-mode fiber (FMF) coupler made with a phase mask method, we
      excite the LP01 mode in an FMF under the test as an input mode, and then we
      detect backward Rayleigh scattered LP11a or LP11b modes, which were generated as
      a result of the mode coupling through the coupler. The mode coupling distribution
      between the LP01 and LP11a,b modes along the test FMF was successfully measured
      with a 10-m spatial resolution by obtaining the ratio between the backscattered
      LP01 mode and LP11a or LP11b. The value of the mode coupling obtained with the
      present method agreed well with that obtained with the conventional transmission
      method.

PMID- 25607079
TI  - 120 Gbit/s injection-locked homodyne coherent transmission of polarization
      multiplexed 64 QAM signals over 150 km.
AB  - We describe an injection-locked 64 QAM homodyne coherent transmission, which is
      the highest QAM multiplicity realized with an injection locking technique. The
      frequency locking range of the local oscillator (LO) was as wide as 1 GHz. The
      phase noise was only 0.2 deg, which is 1/3 of that obtained with our previous
      OVCO-based OPLL (0.6 deg.). As a result, a 120 Gbit/s polarization-multiplexed 64
      QAM signal was successfully transmitted over 150 km with a simple receiver
      configuration and low DSP complexity. 

PMID- 25607080
TI  - Novel laser machining of optical fibers for long cavities with low birefringence.
AB  - We present a novel method of machining optical fiber surfaces with a CO2 laser
      for use in Fiber-based Fabry-Perot Cavities (FFPCs). Previously FFPCs were prone
      to large birefringence and limited to relatively short cavity lengths (<= 200
      MUm). These characteristics hinder their use in some applications such as cavity
      quantum electrodynamics with trapped ions. We optimized the laser machining
      process to produce large, uniform surface structures. This enables the cavities
      to achieve high finesse even for long cavity lengths. By rotating the fibers
      around their axis during the laser machining process the asymmetry resulting from
      the laser's transverse mode profile is eliminated. Consequently we are able to
      fabricate fiber mirrors with a high degree of rotational symmetry, leading to
      remarkably low birefringence. Through measurements of the cavity finesse over a
      range of cavity lengths and the polarization dependence of the cavity linewidth,
      we confirmed the quality of the produced fiber mirrors for use in low
      birefringence FFPCs.

PMID- 25607081
TI  - Significance of scattering by oceanic particles at angles around 120 degree.
AB  - Field observations and theoretical studies have shown that shapes of the volume
      scattering functions (VSFs) of oceanic particles in the backward directions,
      i.e., VSFs normalized by the total backscattering coefficient, exhibit a
      surprisingly low variability at angles near 120 degree, which is also confirmed
      by measurements of VSFs in coastal waters around the US. To investigate what this
      minimum variability angle (theta*) represents, we estimated mean values of the
      VSFs in the backward angles using four mean value theorems: mean value for
      integral, weighted mean value for integral, classic mean value for
      differentiation and Cauchy's mean value. We also estimated the angles
      corresponding to the minimum values of the VSFs. We found theta* to be very close
      to the angles representing the classic mean values for differentiation of the
      VSFs. The low variability is due to the fact that the classic mean values vary
      little with the composition and sizes of particles.

PMID- 25607082
TI  - Evaluation of channel capacities of OAM-based FSO link with real-time wavefront
      correction by adaptive optics.
AB  - We have evaluated the channel capacity of OAM-based FSO link under a strong
      atmospheric turbulence regime when adaptive optics (AO) are employed to correct
      the wavefront phase distortions of OAM modes. The turbulence is emulated by the
      Monte-Carlo phase screen method, which is validated by comparison with the
      theoretical phase structure function. Based on that, a closed-loop AO system with
      the capability of real-time correction is designed and validated. The simulation
      results show that the phase distortions of OAM modes induced by turbulence can be
      significantly compensated by the real-time correction of the properly designed
      AO. Furthermore, the crosstalk across channels is reduced drastically, while a
      substantial enhancement of channel capacity can be obtained when AO is deployed. 

PMID- 25607083
TI  - Influence of methyl red as a dopant on the electrical properties and device
      performance of liquid crystals.
AB  - The ionic effect in nematic liquid-crystal (LC) cells containing the azo dye
      methyl red was investigated by means of dielectric spectroscopy, measurements of
      voltage holding ratio (VHR) and ultraviolet/visible absorption spectroscopy. The
      experimental results indicated that incorporating a minute amount of the methyl
      red (< 0.03 wt%) in the LC host leads to the suppression of the ionic effect
      caused by impurity ions. Practically, the doped LC cells with a dye content of
      0.02 wt% showed improved VHR and promoted lifetime by 15% and 180%, respectively,
      in virtually no expense of the optical transmittance. 

PMID- 25607084
TI  - Integrated photonic reservoir computing based on hierarchical time-multiplexing
      structure.
AB  - An integrated photonic reservoir computing (RC) based on hierarchical time
      multiplexing structure is proposed by numerical simulations. A micro-ring array
      (MRA) is employed as a typical time delay implementation of RC. At the output
      port of the MRA, a secondary time-multiplexing is achieved by multi-mode
      interference (MMI) splitter and delay line array. This hierarchical time
      multiplexing structure can ensure a large reservoir size with fast processing
      speed. Simulation results indicate that the proposed RC system yields better
      performance than previously reported ones. The achieved normalized mean square
      error between the system output and target sequence are 0.5% and 2.7% for signal
      classification and chaotic time series prediction, respectively, while the sample
      rate is as high as 1.3 Gbps.

PMID- 25607085
TI  - Polarization rotation Bragg grating using Si wire waveguide with non-vertical
      sidewall.
AB  - We report polarization independent Bragg grating wavelength filter using
      polarization rotation. A non-vertical waveguide sidewall and antisymmetric
      grating structure can be used to generate the polarization rotation of the
      fundamental modes. The diffraction efficiencies and peaks becomes the same for
      two orthogonal input polarizations. The concept was verified by simulation and
      experiment. 

PMID- 25607086
TI  - High average power mode-locked figure-eight Yb fibre master oscillator.
AB  - For the first time, we demonstrate the possibility to generate record-high output
      radiation power exceeding 1 W in an all-fibre figure-eight mode-locked Yb fibre
      master oscillator based on non-linear amplifying loop mirror. Generated at the
      repetition rate of 25 MHz clusters of sub-pulses with duration of no more than
      200 fs have envelope width of 23 ps or less. Two typical mode-locked laser
      regimes with substantially different generation spectra are identified and
      results of their study presented. Numerical modelling of laser generation in the
      proposed layout agrees well with the measured experimental data. 

PMID- 25607087
TI  - Phase recovery from interferograms under high amplitude vibrations.
AB  - A phase recovery procedure using interferograms acquired in highly noisy
      environments as severe vibrations is described. This method may be implemented
      when disturbances do not allow obtaining equidistant phase shifts between
      consecutive interferograms due to tilt-shift and nonlinearity errors introduced
      by the vibrating conditions. If the amount of the tilt-shift is greater than pi
      radians, it will lead a sign change in the phase estimation. This situation
      cannot be handled correctly by algorithms that consider small errors or non
      equidistant phase shifts during the phase shifting process under moderate
      disturbances. In experimental applications, it is observed that the tilt-shift is
      often the most dominant error in phase differences that one must deal with. In
      this work, a Fourier technique is used for the processing and recovering of the
      cosine of the phase differences. Once the phase differences are obtained, the
      phase encoded in the interferograms is determined. The proposed algorithm is
      tested in two sets of interferograms obtained from the analysis of an optical
      component, finding an rms error in the phase reconstructions of 0.1388 rad. 

PMID- 25607088
TI  - High performance twisted nematic liquid crystal display with solution-derived YZO
      surface modification via ion-beam irradiation.
AB  - Solution-derived YZO films were investigated as liquid crystal (LC) alignment
      layers modified by ion beam (IB) irradiation. Solution processing was adopted in
      place of the sputtering method for the deposition of YZO films as LC alignment
      layers. Uniform and homogeneous LC alignment was achieved to produce a high
      performance LC system. X-ray photoelectron spectroscopy analysis showed that
      surface reformation of YZO films by annealing and IB irradiation affects the
      uniformity of the LC alignment. Superior electro-optical characteristics of
      twisted nematic LC cells constructed from IB-irradiated YZO films were observed,
      which indicates that the proposed solution-derived YZO films have strong
      potential for use in the production of advanced LC displays. 

PMID- 25607089
TI  - Continuous-wave and passive Q-switching laser performance of Yb:YSGG crystal.
AB  - We report, for the first time, on the passive Q-switching laser performance of
      Yb:YSGG disordered garnet crystal. An average output power of 2.6 W at 1025.8 nm
      was produced at a pulse repetition rate of 11 kHz with a slope efficiency of 47%;
      the resulting pulse energy, duration, and peak power were respectively 236 MUJ,
      3.6 ns and 65.6 kW. The laser performance in continuous-wave mode under 935-nm
      diode pumping was also investigated, with output coupling changed over a wide
      range from 0.5% to 60%.

PMID- 25607090
TI  - Lasing from fluorescent protein crystals.
AB  - We investigated fluorescent protein crystals for potential photonic applications,
      for the first time to our knowledge. Rod-shaped crystals of enhanced green
      fluorescent protein (EGFP) were synthesized, with diameters of 0.5-2 MUm and
      lengths of 100-200 MUm. The crystals exhibit minimal light scattering due to
      their ordered structure and generate substantially higher fluorescence intensity
      than EGFP or dye molecules in solutions. The magnitude of concentration quenching
      in EGFP crystals was measured to be about 7-10 dB. Upon optical pumping at 485
      nm, individual EGFP crystals located between dichroic mirrors generated laser
      emission with a single-mode spectral line at 513 nm. Our results demonstrate the
      potential of protein crystals as novel optical elements for self-assembled, micro
      or nano-lasers and amplifiers in aqueous environment.

PMID- 25607091
TI  - Convenient ultra-broadband femtosecond optical gating utilizing transient beam
      deflection effect.
AB  - A simple but robust ultra-broadband femtosecond optical gating method utilizing
      transient beam deflection effect is demonstrated with direct CCD imaging of the
      distorted single-color probe and the measurement of the chirp structure of a
      white light continuum generated from a CaF2 plate. The non-collinear configured
      beam deflection gating technique not only preserves all the advantages of the
      previous optical Kerr lens based gating methods, such as having no phase matching
      conditions, little dependence on probe intensity or special nonlinear media, and
      no requirements on the pump-probe polarization relationship, but it also extends
      the measurable probe bandwidth. Meanwhile, it is also proved that the current
      gating technique is easy-aligned, free from the influence of the pump-probe pulse
      front mismatch and the probe beam profile, which is much convenient for the
      characterization of ultra-broadband light pulses in the applications of ultrafast
      spectroscopy.

PMID- 25607092
TI  - Phase-space measurement for depth-resolved memory-effect imaging.
AB  - Random scattering of light by a turbid layer prevents conventional imaging of
      objects hidden behind it. Angular correlations in the scattered light, created by
      the so-called optical memory effect, have been shown to enable computational
      image retrieval of hidden sources. However, basic memory-effect imaging contains
      no spatial (x) information, as only angular (k-space) measurements are made.
      Here, we use windowed Fourier transforms to record scattered-light images in the
      full {x,k} phase space. The result is the ability to discriminate size and depth
      of individual sources that are hidden behind a thin scattering layer. 

PMID- 25607093
TI  - Anti-diffracting beams through the diffusive optical nonlinearity.
AB  - Anti-diffraction is a theoretically predicted nonlinear optical phenomenon that
      occurs when a light beam spontaneously focalizes independently of its intensity.
      We observe anti-diffracting beams supported by the peak-intensity-independent
      diffusive nonlinearity that are able to shrink below their diffraction-limited
      size in photorefractive lithium-enriched potassium-tantalate-niobate (KTN:Li). 

PMID- 25607094
TI  - Decoupling chaotic amplification and nonlinear phase in high-energy thin-disk
      amplifiers for stable OPCPA pumping.
AB  - The dynamics of chirped pulse amplification in thin-disk regenerative amplifiers
      relevant to the pumping of optical parametric chirp pulse amplification systems
      are described. It is shown that the suitability for reproducible pumping of
      subsequent nonlinear processes requires a balance between the demands of avoiding
      chaotic pulse train dynamics and providing a reproducible spectral phase. We
      describe measures that may be taken to ensure that a laser system operates in the
      desired stable regime. 

PMID- 25607095
TI  - Super multi-view three-dimensional display through spatial-spectrum time
      multiplexing of planar aligned OLED microdisplays.
AB  - Existing super multi-view (SMV) technologies depend on ultra-high resolution two
      dimensional (2D) display panel or large number of 2D display panels to obtain
      dense sub-viewing-zones for constructing more natural three-dimensional (3D)
      display by pure spatial-multiplexing. Through gating the spatial-spectrum of each
      OLED microdisplay, the present work proposes a new SMV technology combining time-
      and spatial-multiplexing based on planar-aligned OLED microdisplays. The inherent
      light emission characteristics of OLED, i.e. large divergence angle, guarantees a
      homogeneous light intensity distribution on the spectrum plane, which is a
      necessary condition for successful time multiplexing. The developed system bears
      with low requirements on the number of 2D display panels. The factors influencing
      the lateral display resolution limit are discussed and the optimum value is
      deduced. Experimentally, a prototype system with 60 sub-viewing-zones is
      demonstrated by 12 OLED microdisplays. The horizontal interval between adjacent
      sub-viewing-zones is 1.6mm.

PMID- 25607096
TI  - Three-dimensional graphene based passively mode-locked fiber laser.
AB  - We present an all-fiber passively mode-locked fiber laser incorporating three
      dimensional (3D) graphene as a saturable absorber (SA) for the first time to the
      best of our knowledge. The 3D graphene is synthesized by template-directed
      chemical vapor deposition (CVD). The SA is then simply formed by sandwiching the
      freestanding 3D graphene between two conventional fiber connectors without any
      deposition process. It is demonstrated that such 3D graphene based SA is capable
      to produce high quality mode-locked pulses. A passively mode-locked fiber laser
      is constructed and stable output pulses with a fundamental repetition rate of
      ~9.9 MHz and a pulse width of ~1 ps are generated from the fiber laser. The
      average output power of the laser is ~10.5 mW while the output pulse is operating
      at single pulse region. The results imply that the freestanding 3D graphene can
      be applied as an effective saturable absorption material for passively mode
      locked lasers. 

PMID- 25607097
TI  - Thin-film limit formalism applied to surface defect absorption.
AB  - The thin-film limit is derived by a nonconventional approach and equations for
      transmittance, reflectance and absorptance are presented in highly versatile and
      accurate form. In the thin-film limit the optical properties do not depend on the
      absorption coefficient, thickness and refractive index individually, but only on
      their product. We show that this formalism is applicable to the problem of
      ultrathin defective layer e.g. on a top of a layer of amorphous silicon. We
      develop a new method of direct evaluation of the surface defective layer and the
      bulk defects. Applying this method to amorphous silicon on glass, we show that
      the surface defective layer differs from bulk amorphous silicon in terms of light
      soaking. 

PMID- 25607098
TI  - Investigation of UV optical fibers under synchrotron irradiation.
AB  - The focus of the present paper deals, for the first time, with commercial UV
      optical fibers, characterizing their behaviour as they are subjected to very high
      flux wiggler generated synchrotron radiation. Five distinct types of UV optical
      fibers, produced by three manufactures, were exposed to total doses between 5 Gy
      and 2000 Gy. The exposure to synchrotron radiation was performed in two
      campaigns. The tests were run off-line and considered the dependence of the
      radiation induced attenuation (RIA) as function of the total dose. The recovery
      of the radiation induced colour centres was studied at room temperature and after
      heating the samples up to 560 K. As a premiere, we also investigated through THz
      imaging and spectroscopy the irradiated optical fiber samples. Under these
      conditions, three of the optical fibers proved to be radiation resistant. The two
      optical fibers sensitive to synchrotron radiation exhibited a linear variation of
      the optical absorption at the wavelengths of lambda = 229 nm, lambda = 248 nm,
      and lambda = 265 nm, for total doses between 60 Gy and 2000 Gy. These two samples
      showed also an increase of the optical absorption in the UV spectral range when
      heated to 560 K. The optical fibers sensitive to synchrotron radiation can
      potentially be used for on-line radiation dosimetry. 

PMID- 25607099
TI  - Frequency non-degenerate phase-sensitive optical parametric amplification based
      on four-wave-mixing in width-modulated silicon waveguides.
AB  - A width-modulated silicon waveguide is proposed to realize non-degenerate phase
      sensitive optical parametric amplification. It is found that the relative phase
      at the input of the phase sensitive amplifier (PSA) thetaIn-PSA can be tuned by
      tailoring the width and length of the second segment of the width-modulated
      silicon waveguide, which will influence the gain in the parametric amplification
      process. The maximum gain of PSA is larger by 9 dB compared with the phase
      insensitive amplifier (PIA) gain, and the gain bandwidth of PSA is larger by 35
      nm compared with the gain bandwidth of PIA. Our on-chip PSA can find important
      potential applications in highly integrated optical circuits for optical chip-to
      chip communication and computers.

PMID- 25607100
TI  - Shaping and spatiotemporal characterization of sub-10-fs pulses focused by a high
      NA objective.
AB  - We describe a setup consisting of a 4f pulse shaper and a microscope with a high
      NA objective lens and discuss the aspects most relevant for an undistorted
      spatiotemporal profile of the focused beam. We demonstrate shaper-assisted pulse
      compression in focus to a sub-10-fs duration using phase-resolved interferometric
      spectral modulation (PRISM). We introduce a nanostructure-based method for sub
      diffraction spatiotemporal characterization of strongly focused pulses. The
      distortions caused by optical aberrations and space-time coupling from the shaper
      can be reduced by careful setup design and alignment to about 10 nm in space and
      1 fs in time. 

PMID- 25607101
TI  - Graphene-based absorber exploiting guided mode resonances in one-dimensional
      gratings.
AB  - A one-dimensional dielectric grating, based on a simple geometry, is proposed and
      investigated to enhance light absorption in a monolayer graphene exploiting
      guided mode resonances. Numerical findings reveal that the optimized
      configuration is able to absorb up to 60% of the impinging light at normal
      incidence for both TE and TM polarizations resulting in a theoretical enhancement
      factor of about 26 with respect to the monolayer graphene absorption (~2.3%).
      Experimental results confirm this behavior showing CVD graphene absorbance peaks
      up to about 40% over narrow bands of a few nanometers. The simple and flexible
      design points to a way to realize innovative, scalable and easy-to-fabricate
      graphene-based optical absorbers. 

PMID- 25607102
TI  - Novel adaptive fiber-optics collimator for coherent beam combination.
AB  - In this manuscript, we experimentally validate a novel design of adaptive fiber
      optics collimator (AFOC), which utilizes two levers to enlarge the movable range
      of the fiber end cap. The enlargement of the range makes the new AFOC possible to
      compensate the end-cap/tilt aberration in fiber laser beam combining system. The
      new AFOC based on flexible hinges and levers was fabricated and the performance
      of the new AFOC was tested carefully, including its control range, frequency
      response and control accuracy. Coherent beam combination (CBC) of two 5-W fiber
      amplifiers array with simultaneously end-cap/tilt control and phase-locking
      control was implemented successfully with the novel AFOC. Experimental results
      show that the average normalized power in the bucket (PIB) value increases from
      0.311 to 0.934 with active phasing and tilt aberration compensation
      simultaneously, and with both controls on, the fringe contrast improves to more
      than 82% from 0% for the case with both control off. This work presents a
      promising structure for tilt aberration control in high power CBC system.

PMID- 25607103
TI  - Varifocal MOEMS fiber scanner for confocal endomicroscopy.
AB  - Based on an advanced silicon optical bench technology with integrated MOEMS
      (Micro-Opto-Electro-Mechanical-System) components, a piezo-driven fiber scanner
      for confocal microscopy has been developed. This highly-miniaturized technology
      allows integration into an endoscope with a total outer probe diameter of 2.5 mm.
      The system features a hydraulically-driven varifocal lens providing axial
      confocal scanning without any translational movement of components. The
      demonstrated resolutions are 1.7 MUm laterally and 19 MUm axially.

PMID- 25607104
TI  - Silicon colors: spectral selective perfect light absorption in single layer
      silicon films on aluminum surface and its thermal tunability.
AB  - Using two most abundant materials in nature: silicon and aluminum, spectral
      selective perfect light absorption in single layer silicon films on aluminum
      surface is demonstrated. Perfect light absorption is achieved due to the critical
      coupling of incident optical wave to the second order resonance mode of the
      optical cavity made of a thin silicon film on aluminum surface. Spectral
      selective perfect light absorption results in different optical colors
      corresponding to different thicknesses of silicon films. The device colors do not
      change when viewing from large angles with respect to the surface normal. Perfect
      absorption wavelength can be tuned over a wide wavelength range over 70 nm by
      thermal annealing. This new technology, which is low cost and compatible with
      silicon technology platform, paves the way for many applications such as optical
      color filters and wavelength selective photodetectors. 

PMID- 25607105
TI  - Reduced graphene oxide for fiber-optic humidity sensing.
AB  - Graphene-based electrical chemical vapor sensors can achieve extremely high
      sensitivity, whereas the comparatively slow sensing response and recovery, the
      research focused on only low concentration detection, have been known as
      drawbacks for many applications requiring rapid and high concentration detection.
      Here we report a novel graphene-based fiber-optic relative humidity (RH) sensor
      relying on fundamentally different sensing mechanism. The sensor can achieve
      power variation of up to 6.9 dB in high relative humidity range (70-95%), and
      display linear response with correlation coefficient of 98.2%, sensitivity of
      0.31 dB/%RH, response speed of faster than 0.13%RH/s, and good repeatability in
      75-95%RH. Theoretical analysis of sensing mechanism can explain the experimental
      result, and reveal the broad applying prospect of the sensor for other kinds of
      chemical vapor detection. This novel graphene-based optical sensor provides a
      beneficial complement to the existing electrical ones, and will promote the
      employment of graphene in chemical sensing techniques. 

PMID- 25607106
TI  - Analysis of diffraction imaging in non-conjugate configurations.
AB  - Diffraction imaging of scattered light allows extraction of information on
      scatterer's morphology. We present a method for accurate simulation of
      diffraction imaging of single particles by combining rigorous light scattering
      model with ray-tracing software. The new method has been validated by comparison
      to measured images of single microspheres. Dependence of fringe patterns on
      translation of an objective based imager to off-focus positions has been analyzed
      to clearly understand diffraction imaging with multiple optical elements. The
      calculated and measured results establish unambiguously that diffraction imaging
      should be pursued in non-conjugate configurations to ensure accurate sampling of
      coherent light distribution from the scatterer. 

PMID- 25607107
TI  - Demonstration of uniform multicore fiber Bragg gratings.
AB  - Fiber Bragg gratings in multicore fibers have significant potential as compact
      and robust filters for research and commercial applications. With the aid of an
      innovative, flat-fielded Mach-Zehnder interferometer, we demonstrate deep (>30
      dB) narrow (100 pm at 3 dB; 90 pm at 10 dB) notches in the outer 6 cores of a 7
      core fiber at a constant wavelength ( +/- 15 pm). This is a crucial step in the
      development of FBGs operating within multimode fibers that carry an arbitrary
      number of spatial modes.

PMID- 25607108
TI  - Diagnosis of monoclonal gammopathy of renal significance.
AB  - Monoclonal gammopathy of renal significance (MGRS) regroups all renal disorders
      caused by a monoclonal immunoglobulin (MIg) secreted by a nonmalignant B-cell
      clone. By definition, patients with MGRS do not meet the criteria for overt
      multiple myeloma/B-cell proliferation, and the hematologic disorder is generally
      consistent with monoclonal gammopathy of undetermined significance (MGUS).
      However, MGRS is associated with high morbidity due to the severity of renal and
      sometimes systemic lesions induced by the MIg. Early recognition is crucial, as
      suppression of MIg secretion by chemotherapy often improves outcomes. The
      spectrum of renal diseases in MGRS is wide, including old entities such as AL
      amyloidosis and newly described lesions, particularly proliferative
      glomerulonephritis with monoclonal Ig deposits and C3 glomerulopathy with
      monoclonal gammopathy. Kidney biopsy is indicated in most cases to determine the
      exact lesion associated with MGRS and evaluate its severity. Diagnosis requires
      integration of morphologic alterations by light microscopy, immunofluorescence
      (IF), electron microscopy, and in some cases by IF staining for Ig isotypes,
      immunoelectron microscopy, and proteomic analysis. Complete hematologic workup
      with serum and urine protein electrophoresis, immunofixation, and serum-free
      light-chain assay is required. This review addresses the pathologic and clinical
      features of MGRS lesions, indications of renal biopsy, and a proposed algorithm
      for the hematologic workup. 

PMID- 25607109
TI  - Update on endocarditis-associated glomerulonephritis.
AB  - Glomerulonephritis (GN) due to infective endocarditis (IE) is well documented,
      but most available data are based on old autopsy series. To update information,
      we now present the largest biopsy-based clinicopathologic series on IE-associated
      GN. The study group included 49 patients (male-to-female ratio of 3.5:1) with a
      mean age of 48 years. The most common presenting feature was acute kidney injury.
      Over half of the patients had no known prior cardiac abnormality. However, the
      most common comorbidities were cardiac valve disease (30%), intravenous drug use
      (29%), hepatitis C (20%), and diabetes (18%). The cardiac valve infected was
      tricuspid in 43%, mitral in 33%, and aortic in 29% of patients. The two most
      common infective bacteria were Staphylococcus (53%) and Streptococcus (23%).
      Hypocomplementemia was found in 56% of patients tested and ANCA antibody in 28%.
      The most common biopsy finding was necrotizing and crescentic GN (53%), followed
      by endocapillary proliferative GN (37%). C3 deposition was prominent in all
      cases, whereas IgG deposition was seen in <30% of cases. Most patients had immune
      deposits detectable by electron microscopy. Thus, IE-associated GN most commonly
      presents with AKI and complicates staphylococcal tricuspid valve infection.
      Contrary to infection-associated glomerulonephritis in general, the most common
      pattern of glomerular injury in IE-associated glomerulonephritis was necrotizing
      and crescentic glomerulonephritis. 

PMID- 25607110
TI  - Progranulin protects against renal ischemia/reperfusion injury in mice.
AB  - Progranulin (PGRN), an autocrine growth factor, has multiple physiological
      functions and is widely involved in the pathogenesis of many types of diseases.
      The pivotal anti-inflammatory function of PGRN in rheumatoid arthritis encouraged
      us to examine the role of PGRN in acute kidney injury (AKI). We found that levels
      of PGRN were significantly reduced in the kidney in a mouse model of renal
      ischemia/reperfusion injury. We also observed that PGRN deficiency (Grn(-/-)
      mice) significantly aggravated renal injury as evidenced by higher serum
      creatinine, more severe morphological injury, increased tubular epithelial cell
      death, and tubulointerstitial neutrophil and macrophage infiltration versus wild
      type mice. In vitro, we found that recombinant human PGRN attenuated hypoxia
      induced inflammatory actions and apoptosis in proximal tubule epithelial cells,
      at least in part associated with a nucleotide-binding oligomerization domain
      containing 2 (NOD2)-mediated immune response. Importantly, pretreatment with or
      delayed administration of recombinant human PGRN protected against or promoted
      recovery from renal ischemia/reperfusion injury in wild-type and Grn(-/-) mice.
      Similar protective effects were also found in cisplatin-induced AKI. Thus, our
      findings provide a better understanding of the biological activities of PGRN in
      the kidney and suggest that PGRN may be an innovative therapeutic strategy for
      treating patients with AKI. 

PMID- 25607111
TI  - Molecular markers to assess short-term disease local recurrence in nasopharyngeal
      carcinoma.
AB  - An important challenge in nasopharyngeal carcinoma (NPC) research is to develop
      effective predictors of tumor recurrence following treatment to determine whether
      immediate adjuvant therapy is necessary. We retrospectively analyzed archived
      specimens collected from 45 patients with paired samples of primary NPC (pNPC)
      and recurrent NPC (rNPC). Clinical samples were collected from the Cancer Center
      Databases of the First People's Hospital of Foshan and Shantou Central Hospital
      (affiliates of Sun Yat-Sen University) between 2001 and 2012. Expression levels
      of phosphor-Stat3 (p-Stat3), signalosome complex subunit 5 (Jab1/Csn5), Akt1,
      C/EBP homologous protein (CHOP), Ki-67, and apoptosis were determined by
      immunohistochemistry in pNPC and rNPC samples from the same patients. Differences
      in these markers between the short-term interval to recurrence (ITR) group (ITR
      <18 months) and long-term ITR group (ITR >=18 months) were further analyzed. In
      Cox's regression analysis, the ITR was significantly associated as an independent
      negative prognostic factor for overall survival (hazard ratio, 0.211; 95%
      confidence interval, 0.053-0.841; P=0.027). p-Stat3 was increased in the short
      term ITR group (ITR <18 months) and tended to be lower in the long-term ITR group
      (ITR >=18 months). In the short-term ITR group, nuclear Akt expression was
      significantly increased in paired rNPC (P=0.028). In the long-term ITR group, the
      expression of nuclear Jab1/Csn5 (P=0.047) and assessment of apoptosis measured
      with TdT-mediated dUTP nick end-labeling (TUNEL) (P=0.003) was significantly
      increased in paired rNPC. The results suggest that differences between short- and
      long-term ITR may predict outcome in rNPC. Furthermore, the overexpression of
      Jab1/Csn5 and Akt may contribute to the carcinogenesis of rNPC, and Akt seems to
      promote the progression of short-term ITR. Intra-individual changes of Jab1/Csn5,
      Akt, and TUNEL may help to identify short-term ITR.

PMID- 25607113
TI  - Organisational development in a rural hospital in Australia.
AB  - OBJECTIVE: This paper analyses an organisational development project that aimed
      to change the organisational culture and improve people management systems and
      processes. The questions addressed were: was the change process a success; how
      was success defined; and what were the barriers to its progress? METHODS: We
      examined the process of change over a 3-year period. The organisational
      development intervention is described and analysed. Qualitative methods,
      including document review, in-depth interviews and focus groups, participant
      observation, newsletters and diary entries were used to gather the data. A
      variant of competing values was used to analyse the data. RESULTS: We sought to
      build trust with all managers and encouraged reflection by conducting feedback
      sessions, presentations, workshops and one-on-one and group discussions. A cross
      site action group was established to encourage organisation-wide participation in
      the project. However, it was clear that stakeholders had different understandings
      and perceptions of the problems facing the organisation. The project faltered
      when a leadership development intervention was organised. CONCLUSIONS: The
      existence of at least four different organisational 'worlds' and identities,
      according to different professional groupings with different goals, languages and
      values, was evident. The relationship between the researcher and subjects was key
      in terms of whether the researcher is seen as an 'expert' or as a 'facilitator'.
      In bringing about change, we need to work with the Chief Executive Officer in
      empowering others. Hence, the researchers need to engage in continual dialogue
      across boundaries and within groups as well as at individual levels to provide
      support for organisational change.

PMID- 25607112
TI  - Azithromycin attenuates cigarette smoke extract-induced oxidative stress injury
      in human alveolar epithelial cells.
AB  - Cigarette smoking has been verified to be one of the most important etiological
      factors causing the development of bronchogenic carcinoma and chronic obstructive
      pulmonary disease. Azithromycin (AZM) has been demonstrated to have antioxidant
      capacity. In the present study, whether AZM is able to attenuate cigarette smoke
      extract (CSE)-induced A549 cell oxidative stress injury was investigated. Cells
      were incubated with CSE in the presence or absence of AZM. Cell viability was
      measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. The expression of vascular endothelial growth factor (VEGF) was analyzed
      using western blotting and ELISA. The expression of epithelial cell structural
      proteins, zona occludens (ZO)-1 and occludin was determined using western
      blotting and immunofluorescence staining. Reactive oxygen species (ROS)
      production was examined by flow cytometry and fluorescence staining. The results
      demonstrated that the exposure of A549 cells to CSE decreased cell viability in a
      dose- and time-dependent manner. AZM significantly attenuated the CSE-induced
      decreases in the expression of VEGF and epithelial cell structural proteins,
      including ZO-1 and occludin. CSE also stimulated ROS production in the A549 cell,
      while AZM significantly reversed the effects of CSE. In addition, the inhibition
      of ROS by N-acetyl-L-cysteine had similar effects as AZM on the expression of
      VEGF and epithelial cell structural proteins and also enhanced cell
      proliferation. In conclusion, AZM attenuated CSE-induced oxidative stress injury
      in A549 cells and may be a promising therapeutic agent for smoking-associated
      pulmonary diseases.

PMID- 25607114
TI  - Resistance of SMMC-7721 hepatoma cells to etoposide in hypoxia is reversed by
      VEGF inhibitor.
AB  - Hypoxia is associated with resistance to chemotherapy in a number of human cancer
      types; particularly in hepatocellular carcinoma (HCC), which is a highly
      vascularized tumor. To develop a potential combination therapy strategy that is
      capable of overcoming the hypoxia-induced insensitivity to chemotherapy, the HCC
      cell SMMC-7721 was employed to investigate the hypoxia-induced chemoresistance to
      etoposide. Increased levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and
      vascular endothelial growth factor (VEGF) were observed when SMMC-7721 cells were
      exposed to hypoxia, and exposure of tumor cells to hypoxia impaired etoposide
      induced DNA damage, as indicated by the failure of upregulation of gammaHA2X.
      Etoposide-induced apoptosis and cell cycle arrest of SMMC-7721 was also impaired
      in hypoxia. However, co-treatment with anti-VEGF significantly restored etoposide
      induced cell apoptosis and cell cycle arrest, as indicated by the elimination of
      B-cell lymphoma 2 (Bcl-2), procaspase 3, cyclin B1 and Cdc2. Furthermore, anti
      VEGF eliminated phosphorylation of AKT, ERK and IkappaB-alpha resulting from
      hypoxia, suggesting the involvement of VEGF in the activation of the survival
      pathways. In conclusion, the present study suggests a significant role of VEGF in
      the chemoresistance of etoposide in hypoxia. A rational chemotherapy should be
      developed based on a combination of etoposide and anti-VEGF.

PMID- 25607115
TI  - Polymorphism in the NLRP3 inflammasome-associated EIF2AK2 gene and inflammatory
      bowel disease.
AB  - Inflammatory bowel disease (IBD) is the common name for numerous relapsing
      inflammatory conditions, and is the collective name for Crohn's disease (CD) and
      ulcerative colitis (UC). The activation of the inflammasome in the pathogenesis
      of IBD has recently been identified, however the underlying mechanisms remain
      unclear. An activator of the inflammasome is double-stranded RNA-dependent
      protein kinase R, also termed EIF2AK2. A genetic alteration in the EIF2AK2 gene
      has previously been shown to be associated with Alzheimer's disease. The present
      study genotyped samples from a Swedish cohort of patients with IBD and healthy
      controls for an EIF2AK2 polymorphism. The rs2254958 polymorphism in the 5'
      untranslated region of the EIF2AK2 gene was genotyped by TaqMan(r) single
      nucleotide polymorphism genotyping, followed by allelic discrimination. However,
      no significant association was determined between the rs2254958 polymorphism and
      the development of IBD, or clinical outcome. In conclusion, the results of the
      present study suggest that the rs2254958 polymorphism has a limited effect on the
      onset or progression of IBD. 

PMID- 25607116
TI  - Chemicals as a source of autoimmune reactivity.

PMID- 25607117
TI  - Effects of jazz on postoperative pain and stress in patients undergoing elective
      hysterectomy.
AB  - CONTEXT: Anesthesiologists use various medications to provide surgical patients
      with pain relief in the postoperative period. Other modalities, such as music,
      could be used in conjunction with opioids and nonsteroidal anti-inflammatory
      drugs (NSAIDs) to decrease pain and lower heart rate and blood pressure. Our
      hypothesis was that patients listening to jazz in a postanesthesia care unit
      (PACU) would have lower heart rates and blood pressures and reduced pain and
      anxiety. OBJECTIVE: The study objective was to determine if listening to jazz
      music in the PACU, when compared to wearing noise-canceling headphones with no
      music playing, would decrease heart rate, blood pressure, pain, or anxiety in
      patients undergoing a hysterectomy. DESIGN: The research design was a
      prospective, randomized study. SETTING: The study was conducted in the PACU at
      the Penn State Hershey Medical Center in Hershey, PA, USA. PARTICIPANTS: A total
      of 56 patients, aged 18-75 y, who were categorized as status 1 or 2 according to
      the American Society of Anesthesiologists (ASA) Physical Status Classification
      System, and who were undergoing elective laparoscopic or abdominal
      hysterectomies, were enrolled in the study. INTERVENTION: Patients were randomly
      assigned either to listen to jazz music where the beats per min (BPM) was <100
      (experimental group, n = 28) or to wear noise-canceling headphones (control
      group, n = 28) for 30 min while in the PACU after their surgery. OUTCOME
      MEASURES: Heart rate was the primary outcome, and secondary outcomes included
      systolic and diastolic blood pressure, an anxiety score, and a pain score. All
      outcome measures were initially recorded at baseline upon the patient's arrival
      in the PACU. Heart rate and blood pressure were recorded postoperatively every 5
      min for the initial 30 min that a patient was in the PACU. Pain was checked every
      10 min during the 30-min period; anxiety was checked at 30 min. RESULTS: Heart
      rates of patients in the noise-cancellation group were significantly lower when
      compared with baseline (P < .05), at all time points. For patients in the jazz
      group, heart rates were significantly lower at 15, 20, 25, and 30 min when
      compared with baseline. The pain scores were significantly lower (P < .05) in the
      noise-cancellation group compared with the jazz group at 10 min into the recovery
      period. CONCLUSION: Overall, the results showed that patients responded not only
      to music but also to silence in the PACU. Using music and/or noise reduction
      could decrease opioid administration, promote relaxation, and improve patient
      satisfaction.

PMID- 25607118
TI  - Effects of energy enhancer patches on cortisol production, peripheral
      circulation, and psychological measures: a pilot study.
AB  - CONTEXT: LifeWave Energy Enhancer (LEE) patches (LifeWave Corp, San Diego, CA,
      USA) on skin produce some changes that are consistent with increased energy
      production, but little is known about their effects on cortisol concentrations or
      the peripheral circulation. OBJECTIVE: The study intended to assess the effects
      of LEE patches on salivary cortisol, peripheral circulation, and psychological
      measures on healthy adults. METHODS: A double-blind, placebo-controlled,
      randomized pilot study was performed. SETTING/LOCATION: Measurements were made in
      the laboratory at Mind-Body-Science (Tucson, AZ, USA). Participants collected
      some of the saliva samples at work or home. PARTICIPANTS: To obtain pilot data,
      20 healthy individuals with no chronic conditions were recruited-5 males and 15
      females-aged 30-69 y. INTERVENTION: Participants completed baseline psychological
      questionnaires and provided saliva samples for hormonal analysis. The next day,
      fingertip microvascular perfusion was measured, LEE or placebo patches were
      applied to participants' wrists, and perfusion scans were repeated, first
      immediately after and then 10 min after application of the patch. Saliva samples
      were collected, and questionnaires were completed. Participants returned at noon
      and 4:00 PM for further scans, and at the end of that time, the patches were
      removed. The protocol was repeated the following day using new patches. OUTCOME
      MEASURES: The research team analyzed the saliva samples for levels of cortisol
      and measured the percentage changes in cutaneous microvascular perfusion. The
      participants completed the energy visual analog scales (eVASs) and the Marlowe
      Crowne Social Desirability survey. RESULTS: After the first patch application,
      the active group showed significantly higher cortisol concentrations than the
      placebo group, both at noon-2.39 +/- 0.17 ng/mL vs 2.15 +/- 0.27 (P = .0360),
      respectively-and at 4:00 PM- 2.02 +/- 0.24 vs 1.67 +/- 0.31 (P = .0155),
      respectively. No consistent changes occurred in perfusion. The eVAS score
      decreased significantly compared with baseline in the placebo group but not in
      the active group. CONCLUSION: Cortisol concentrations and eVAS scores showed
      significant differences between groups, which is consistent with the patches
      increasing energy production, warranting further testing.

PMID- 25607119
TI  - Rhythmic breathing: immunological, biochemical, and physiological effects on
      health.
AB  - Yoga and breathing techniques have become increasingly popular in recent decades.
      Sudarshan Kriya (SK) is a type of rhythmic and controlled breathing that involves
      cyclic breathing in which long breaths are followed by medium and short breaths.
      Scientific research has been conducted to study the effects of SK on different
      physiological parameters. Various studies have shown that the technique is simple
      and cost effective and can be used as a complementary therapy, together with
      ongoing conventional treatments, to help people suffering from extreme levels of
      stress, anxiety, and other physical problems. Studies have demonstrated that SK
      can play an important role in promoting a healthy lifestyle by improving
      immunity, antioxidant status, hormonal status, and brain functioning. Through
      available scientific evidence and research, the current article aims to review
      the complementary role of rhythmic breathing (ie, SK) as a practical and
      effective tool to alleviate stress, improve health, and increase wellness.

PMID- 25607121
TI  - Rubin Naiman, PhD: Sleep and the spectrum of consciousness--learning to love
      sleep and dreams.

PMID- 25607120
TI  - A healthy aging program for older adults: effects on self-efficacy and morale.
AB  - CONTEXT: As of 2012, 810 million people worldwide were older than 60 y,
      accounting for 11% of the population. That number is expected to rise to 2
      billion by 2050 or to 22% of the overall population. As a result, a growing need
      exists to understand the factors that promote mental and physical health in older
      populations. OBJECTIVES: The purpose of this study was to develop a healthy aging
      program for older adults and to measure the changes from baseline to the end of
      the program in participants' relevant psychosocial outcomes (ie, self-efficacy
      and morale). DESIGN: The study's healthy aging mind-body intervention (MBI) was
      adapted from the Relaxation Response Resiliency Program (3RP) at the Benson-Henry
      Institute for Mind Body Medicine, which incorporates elements from the fields of
      stress management, cognitive behavioral therapy, and positive psychology. That
      program was modified with examples and exercises targeted to an older population
      and evaluated in the current single-arm pilot study. SETTING: The program took
      place at the Massachusetts General Hospital (MGH). PARTICIPANTS: The 9-wk healthy
      aging MBI was developed for participants aged 65 y and older. Fifty-one older
      adults from the surrounding community participated in the study's groups.
      INTERVENTION: A new intervention group began the program every 3 mo, with a
      maximum of 12 individuals per group. For each group, the MBI consisted of weekly
      90-min sessions for 9 consecutive wk, directed by a psychologist. The program
      included sessions that taught participants (1) a variety of methods to elicit the
      relaxation response (RR), (2) the practice of adaptive coping and cognitions, (3)
      behaviors necessary to create a healthy lifestyle, and (4) methods of building
      social support. OUTCOME MEASURES: The research team chose to focus on 2
      psychological variables of interest for aging populations: morale and self
      efficacy. The study used 2 questionnaires to measure those outcomes, the
      Philadelphia Geriatric Center Morale Scale (PGCMS), a multidimensional measure of
      the psychological state of older people, and the Coping Self-efficacy Scale
      (CSES), a measure that addresses the multiple dimensions of self-efficacy.
      RESULTS: Data from 5 intervention groups were combined for the current analysis.
      Forty-six participants enrolled and completed questionnaires. Of those
      participants, 41 attended at least 7 of the 9 sessions. Significant increases in
      self-efficacy and morale were observed for program completers. After a highly
      conservative sensitivity analysis, the change for the measure of self-efficacy
      remained significant, and the change for the measure of morale trended toward
      significance. CONCLUSIONS: The study's healthy aging program appears to be a
      feasible intervention for older adults, with the potential to increase levels of
      self-efficacy and morale in participants. Further research is warranted to
      determine its effects on other psychosocial outcomes and health care utilization
      in aging populations.

PMID- 25607122
TI  - Primary and secondary prevention of metabolic and cardiovascular comorbidities in
      women with polycystic ovary syndrome.

PMID- 25607123
TI  - Pregnancy in women undergoing hemodialysis: case series in a Southeast Brazilian
      reference center.
AB  - PURPOSE: To describe maternal and neonatal outcomes in pregnant women undergoing
      hemodialysis in a referral center in Brazilian Southeast side. METHODS:
      Retrospective and descriptive study, with chart review of all pregnancies
      undergoing hemodialysis that were followed-up at an outpatient clinic of high-
      risk prenatal care in Southeast Brazil. RESULTS: Among the 16 women identified, 2
      were excluded due to follow-up loss. In 14 women described, hypertension was the
      most frequent cause of chronic renal failure (half of cases). The majority
      (71.4%) had performed hemodialysis treatment for more than one year and all of
      them underwent 5 to 6 hemodialysis sessions per week. Eleven participants had
      chronic hypertension, 1 of which was also diabetic, and 6 of them were smokers.
      Regarding pregnancy complications, 1 of the hypertensive women developed
      malignant hypertension (with fetal growth restriction and preterm delivery at 29
      weeks), 2 had acute pulmonary edema and 2 had abruption placenta. The mode of
      delivery was cesarean section in 9 women (64.3%). All neonates had Apgar score at
      five minutes above 7. CONCLUSIONS: To improve perinatal and maternal outcomes of
      women undergoing hemodialysis, it is important to ensure multidisciplinary
      approach in referral center, strict control of serum urea, hemoglobin and
      maternal blood pressure, as well as close monitoring of fetal well-being and
      maternal morbidities. Another important strategy is suitable guidance for
      contraception in these women.

PMID- 25607124
TI  - [Can genital infections alter the results of preterm birth predictive tests?].
AB  - PURPOSE: To determine if the presence of infectious agents in vaginal or cervical
      content can alter the results of the insulin-like growth factor binding protein-1
      (phIGFBP-1) test and the measurement of cervical length (CC) by transvaginal
      ultrasonography. METHODS: A total of 107 pregnant women with a history of
      spontaneous preterm birth were submitted to the phIGFBP-1 test and to measurement
      of CC by transvaginal ultrasonography every 3 weeks, between 24 and 34 weeks of
      gestation. Genital infections were determined immediately before testing. The
      patients were distributed into four groups (GA, GB, GC, and GD) and the
      correlation between genital infection and changes in the tests was determined
      within each group based on the odds ratio (OR) and the Pearson correlation
      coefficient. RESULTS: In each group, over 50% of the patients had genital
      infections (GA 10/17; GB 28/42; GC 15/24; GD 35/53), with bacterial vaginosis
      being the main alteration of the vaginal flora. Positive results for phIGFBP-1(GA
      10/10; GB 18/28; GC 15/15; GD 19/35) and CC <= 20 mm (GA 10/10; GB 20/28; GC
      10/15; GD 20/35) were obtained more frequently in patients with genital infection
      in all groups. Nonetheless, when applying the Pearson correlation coefficient we
      detected a poor correlation between genital infection and positivity for markers.
      CONCLUSION: The presence of changes in the vaginal flora and of other genital
      infections does not significantly alter the results of phIGFBP-1 and the
      measurement of cervical length when compared to cases without infection. However,
      more studies with larger samples are necessary to confirm these results.

PMID- 25607125
TI  - [Food consumption in postmenopausal women and its relation with anthropometric
      measurements and time since menopause].
AB  - PURPOSE: To evaluate eating in postmenopausal women and its relation to
      anthropometry, age and time since menopause in Sao Bernardo do Campo residents.
      METHODS: During the period from June to August of 2011, 148 postmenopausal women
      residents in state of Sao Paulo (Southeast region of Brazil) were evaluated using
      a structured questionnaire containing socioeconomic, clinical, anthropometric and
      food data. The level of physical activity, biochemical variables, Body Mass Index
      (BMI), abdominal circumference (AC) and dietary intake (energy, protein,
      carbohydrates and fats, fiber, cholesterol, vitamins A and C, minerals, calcium
      and iron) were analyzed according to age and time after menopause. RESULTS: Mean
      BMI was 29.0 <= 5.6 kg/m(2) and abdominal circumference was 95.7 +/- 12.9 cm. The
      average daily caloric consumption was 1,406.3 +/- 476.5 kcal. The calorie intake
      was significantly more appropriate in normal-weight women and women with AC<88
      cm. The same was observed for protein intake (p<0.001 and p=0.006, respectively).
      No association was observed with age or duration of the postmenopausal period,
      except for average protein consumption that was higher in the group with five
      years or less of menopause (p=0.048). CONCLUSION: The anthropometry of
      postmenopausal women showed a predominance of overweight and obesity. Dietary
      intake was adequate in relation to the percentage of calories and macronutrients
      and calories among most normal-weight women and women with AC<88 cm.

PMID- 25607126
TI  - Predictors of fluid intravasation during operative hysteroscopy: a preplanned
      prospective observational study with 200 cases.
AB  - PURPOSE: To verify the predictors of intravasation rate during hysteroscopy.
      METHODS: Prospective observational study (Canadian Task Force classification II(
      1)). All cases (n=200 women; 22 to 86 years old) were treated in an operating
      room setting. Considering respective bag overfill to calculate water balance, we
      tested two multiple linear regression models: one for total intravasation (mL)
      and the other for absorption rate (mL.min(-1)). The predictors tested
      (independent variables) were energy (mono/bipolar), tube patency (with/without
      tubal ligation), hysterometry (cm), age <= 50 years, body surface area (m(2)),
      surgical complexity (with/without myomectomy) and duration (min). RESULTS: Mean
      intravasation was significantly higher when myomectomy was performed (442 +/- 616
      versus 223 +/- 332 mL; p<0.01). In the proposed multiple linear regression models
      for total intravasation (adjusted R(2)=0.44; p<0.01), the only significant
      predictors were myomectomy and duration (p<0.01).In the proposed model for
      intravasation rate (R(2)=0.39; p<0.01), only myomectomy and hysterometry were
      significant predictors (p=0.02 and p<0.01, respectively). CONCLUSIONS: Not only
      myomectomy but also hysterometry were significant predictors of intravasation
      rate during operative hysteroscopy.

PMID- 25607127
TI  - [Prevalence of low bone mineral density in postmenopausal breast cancer
      survivors].
AB  - PURPOSE: To evaluate the prevalence of low bone mineral density (BMD) in
      postmenopausal breast cancer survivors. METHODS: In this cross-sectional study,
      115 breast cancer survivors, seeking healthcare at a University Hospital in
      Brazil, were evaluated. Eligibility criteria included women with amenorrhea >= 12
      months and age >= 45 years, treated for breast cancer and metastasis-free for at
      least five years. BMD was measured by DEXA at the lumbar spine (L1-L4) and
      femoral neck. Low BMD was considered when total-spine and/or femoral-neck T-score
      values were <-1.0 Delphi Score (DP) (osteopenia and osteoporosis). The risk
      factors for low BMD were assessed by interview. Data were analyzed statistically
      by the chi(2) test and Fisher's exact test. RESULTS: The mean age of breast
      cancer survivors was 61.6 +/- 10.1 years and time since menopause was 14.2 +/-
      5.6 years, with a mean follow-up of 10.1 +/- 3.9 years. Considering spine and
      femoral neck, 60% of breast cancer survivors had low BMD. By evaluating the risk
      factors for low BMD, a significant difference was found in the percent
      distribution for age (higher % of women >50 years with low BMD), personal history
      of previous fracture (11.6% with low BMD versus 0% with normal BMD) and BMI. A
      higher frequency of obesity was observed among women with normal BMD (63%)
      compared to those with low BMD (26.1%) (p<0.05). CONCLUSION: Postmenopausal
      breast cancer survivors had a high prevalence of osteopenia and osteoporosis.

PMID- 25607128
TI  - [Preservation of the fertility and the ovaries in women with benign adnexal
      tumors].
AB  - PURPOSE: To evaluate the sparing of fertility and ovaries in women submitted to
      surgical treatment for benign adnexal tumors. METHODS: Between February 2010 and
      January 2014, 206 patients were included in this observational study as they were
      submitted to surgical treatment for benign ovarian tumors at CAISM, a tertiary
      hospital. Fertility sparing surgery was defined as tumorectomy or unilateral
      salpingoophorectomy without hysterectomy in premenopausal women. Preservation of
      the ovary occurred when at least one ovary or part of it was mantained. RESULTS:
      Of the 206 women with benign tumors, 120 (58%) were premenopausal and 86 (42%)
      were postmenopausal. There were 36 (30%) ovarian germ cell tumors, 31 (26%)
      epithelial neoplasms and 11 (9%) sex-cord stromal tumors among premenopausal
      women. In the group of postmenopausal women, 35 (41%) epithelial neoplasms, 27
      (31%) sex-cord stromal tumors and 8 (9%) ovarian germ cell tumors were
      identified. Among 36 women with non-neoplastic ovarian tumors, 21 (58%) had
      endometriomas and 8 (22%) functional cysts. Among 22 women with extra-ovarian
      tumors, uterine leiomyomatosis was the most frequent finding (50%). In the group
      of women who were <= 35 years old, 26 (57%) were treated by tumorectomy and 18
      (39%) were submitted to unilateral salpingoophorectomy with sparing of the uterus
      and the contralateral ovary. Women who were <= 35 years old were more frequently
      operated by laparoscopy which was associated with a higher number of fertility
      sparing procedures when compared to laparotomy (p<0.01). Twenty-six (28%) women
      submitted to hysterectomy with bilateral salpingoophorectomy were premenopausal.
      CONCLUSION: Although there is a trend to perform only tumorectomy in women who
      are <= 35 years old, a significant number of young women is still treated by
      salpingoophorectomy. Among 36- to 45-year-old women, only 70% had their fertility
      spared, while 20% had both ovaries removed. However, whenever possible, we must
      try to preserve the ovaries, mainly in premenopausal women.

PMID- 25607129
TI  - Diagnosis, classification and treatment of gestational trophoblastic neoplasia.
AB  - Gestational trophoblastic neoplasia (GTN) is the term to describe a set of
      malignant placental diseases, including invasive mole, choriocarcinoma, placental
      site trophoblastic tumor and epithelioid trophoblastic tumor. Both invasive mole
      and choriocarcinoma respond well to chemotherapy, and cure rates are greater than
      90%. Since the advent of chemotherapy, low-risk GTN has been treated with a
      single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN,
      however, should be treated with multiagent chemotherapy, and the regimen usually
      selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D,
      cyclophosphamide and vincristine. This study reviews the literature about GTN to
      discuss current knowledge about its diagnosis and treatment. 

PMID- 25607130
TI  - Compact spatial multiplexers for mode division multiplexing.
AB  - Spatial multiplexer (SMUX) for mode division multiplexing (MDM) has evolved from
      mode-selective excitation, multiple-spot and photonic-lantern based solutions in
      order to minimize both mode-dependent loss (MDL) and coupler insertion loss
      (CIL). This paper discusses the implementation of all the three solutions by
      compact components in a small footprint. Moreover, the compact SMUX can be
      manufactured in mass production and packaged to assure high reliability. First,
      push-pull scheme and center launch based SMUXes are demonstrated on two mostly
      popular photonic integration platforms: Silicon-on-insulator (SOI) and Indium
      Phosphide (InP) for selectively exciting LP<sub>01</sub> and LP<sub>11</sub>
      modes. 2-dimensional (2D) top-coupling by using vertical emitters is explored to
      provide a coupling interface between a few-mode fiber (FMF) and the photonic
      integrated SMUX. SOI-based grating couplers and InP-based 45 degrees  vertical
      mirrors are proposed and researched as vertical emitters in each platform.
      Second, a 3-spot SMUX is realized on an InP-based circuit through employing 45
      degrees  vertical mirrors. Third, as a newly-emerging photonic integration
      platform, laser-inscribed 3D waveguide (3DW) technology is applied for a fully
      packaged dual-channel 6-mode SMUX including two 6-core photonic lantern
      structures as mode multiplexer and demultiplexer, respectively. 

PMID- 25607131
TI  - Breakdown of the linear acousto-optic interaction regime in phoxonic cavities.
AB  - The limits of validity of the linear photoelastic model are investigated in a one
      dimensional dual photonic-phononic cavity, formed by alternating layers of a
      chalcogenide glass and a polymer homogeneous and isotropic material, which
      supports both optical and acoustic resonant modes localized in the same region.
      It is shown that the linear-response regime breaks down when either the acoustic
      excitation increases or the first-order acousto-optic interaction coupling
      element vanishes by symmetry, giving rise to the manifestation of multiphonon
      absorption and emission processes by a photon. Our results provide a consistent
      interpretation of different aspects of the underlying physics relating to
      nonlinear acousto-optic interactions that can occur in such cavities. 

PMID- 25607132
TI  - Propagation of electromagnetic stochastic beams in anisotropic turbulence.
AB  - The effects of anisotropic, non-Kolmogorov turbulence on propagating stochastic
      electromagnetic beam-like fields are discussed for the first time. The atmosphere
      of interest can be found above the boundary layer, at high (more than 2 km above
      the ground) altitudes where the energy distribution among the turbulent eddies
      might not satisfy the classic assumption represented by the famous 11/3
      Kolmogorov's power law, and the anisotropy in the direction orthogonal to the
      Earth surface is possibly present. Our analysis focuses on the classic
      electromagnetic Gaussian Schell-model beams but can either be readily reduced to
      scalar and/or coherent beams or generalized to other beam classes. In particular,
      we explore the effects of the anisotropic parameter on the spectral density, the
      spectral degree of coherence and on the spectral degree of polarization of the
      beam. 

PMID- 25607133
TI  - Modulation measuring profilometry with auto-synchronous phase shifting and
      vertical scanning.
AB  - To determine the shape of a complex object with vertical measurement mode and
      higher accuracy, a novel modulation measuring profilometry realizing auto
      synchronous phase shifting and vertical scanning is proposed. Coaxial optical
      system for projection and observation instead of triangulation system is adopted
      to avoid shadow and occlusion. In the projecting system, sinusoidal grating is
      perpendicular to optical axis. For moving the grating along a direction at a
      certain angle to optical axis, 1D precision translation platform is applied to
      achieve purposes of both phase-shifting and vertical scanning. A series of fringe
      patterns with different modulation variations are captured by a CCD camera while
      scanning. The profile of the tested object can be reconstructed by the
      relationship between the height values and the modulation distributions. Unlike
      the previous method based on Fourier transform for 2D fringe pattern, the
      modulation maps are calculated from the intensity curve formed by the points with
      definite pixel coordinates in the captured fringe patterns. The paper gives the
      principle of the proposed method, the set-up of measurement system and the method
      for system calibration. Computer simulation and experiment results proved its
      feasibility. 

PMID- 25607134
TI  - Spectral coherence in all-normal dispersion supercontinuum in presence of Raman
      scattering and direct seeding from sub-picosecond pump.
AB  - Intensity stability and wavelength correlations of near-infrared supercontinuum
      generation are studied in all-normal flattened dispersion, all-solid soft glass
      photonic crystal fiber. We use dispersive Fourier transformation method to
      measure shot-to-shot resolved spectra under pumping from a sub-picosecond, fiber
      based chirped pulse amplification (CPA) system. For the first time to our
      knowledge, we demonstrate how unconverted radiation from pump, propagating in the
      photonic cladding of the fiber, improves the measured degree of coherence in the
      spectrum and influences its wavelength correlation by seeding of multiple four
      wave-mixing / Raman scattering components. The presented results suggest a
      convenient and simple way of stabilizing of shot-to-shot coherence in sub
      picosecond fiber laser pumped, normal-dispersion supercontinuum sources by
      direct, pump-related seeding. 

PMID- 25607135
TI  - White thin-film flip-chip LEDs with uniform color temperature using laser lift
      off and conformal phosphor coating technologies.
AB  - We fabricated a phosphor-conversion white light emitting diode (PC-WLED) using a
      thin-film flip-chip GaN LED with a roughened u-GaN surface (TFFC-SR-LED) that
      emits blue light at 450 nm wavelength with a conformal phosphor coating that
      converts the blue light into yellow light. It was found that the TFFC-SR-LED with
      the thin-film substrate removal process and surface roughening exhibits a power
      enhancement of 16.1% when compared with the TFFC-LED without a sapphire
      substrate. When a TFFC-SR-LED with phosphors on a Cu-metal packaging-base (TFFC
      SR-Cu-WLED) was operated at a forward-bias current of 350 mA, luminous flux and
      luminous efficacy were increased by 17.8 and 11.9%, compared to a TFFC-SR-LED on
      a Cup-shaped packaging-base (TFFC-SR-Cup-WLED). The angular correlated color
      temperature (CCT) deviation of a TFFC-SR-Cu-WLED reaches 77 K in the range of -70
      degrees  to + 70 degrees  when the average CCT of white LEDs is around 4300 K.
      Consequently, the TFFC-SR-LED in a conformal coating phosphor structure on a Cu
      packaging-base could not only increase the luminous flux output, but also improve
      the angular-dependent CCT uniformity, thereby reducing the yellow ring effect. 

PMID- 25607136
TI  - In-fiber torsion sensor based on dual polarized Mach-Zehnder interference.
AB  - This paper presents a novel optical fiber torsion sensor based on dual polarized
      Mach-Zehnder interference (DPMZI). Unlike the conventional fiber sensor, the
      proposed sensor is composed of a sensor part and a demodulator. The demodulator
      is made by a bared single mode fiber (SMF) loop, and the sensor part is a segment
      of a coated SMF placed before the loop. A mathematical model is proposed based on
      DPMZI mechanism and from the model when the sensor part is twisted, the E-field
      rotational angle will bring a quasi-linear impact on the resonance dip wavelength
      in their matched detecting range. A proof-of-concept experiment was performed to
      verify the theoretical prediction. From the experimental data, a sensitivity of 
      0.3703, -1.00962, and -0.59881 nm*m/rad is achieved with the determining range of
      12.0936, 7.6959, and 10.4444 rad/m respectively. The sensor which is composed
      only of the SMF has the advantages of low insertion loss (~-2dB), healthy
      structure, low manufacture cost, and easy assembly and application. 

PMID- 25607137
TI  - Anisotropic effective permittivity of an ultrathin gold coating on optical fiber
      in air, water and saline solutions.
AB  - The optical properties of an ultrathin discontinuous gold film in different
      dielectric surroundings are investigated experimentally by measuring the
      polarization-dependent wavelength shifts and amplitudes of the cladding mode
      resonances of a tilted fiber Bragg grating. The gold film was prepared by
      electron-beam evaporation and had an average thickness of 5.5 nm ( +/- 1 nm).
      Scanning electron imaging was used to determine that the film is actually formed
      of individual particles with average lateral dimensions of 28 nm ( +/- 8 nm). The
      complex refractive indices of the equivalent uniform film in air at a wavelength
      of 1570 nm were calculated from the measurements to be 4.84-i0.74 and 3.97-i0.85
      for TM and TE polarizations respectively (compared to the value for bulk gold:
      0.54-i10.9). Additionally, changes in the birefringence and dichroism of the
      films were measured as a function of the surrounding medium, in air, water and a
      saturated NaCl (salt) solution. These results show that the film has stronger
      dielectric behavior for TM light than for TE, a trend that increases with
      increasing surrounding index. Finally, the experimental results are compared to
      predictions from two widely used effective medium approximations, the generalized
      Maxwell-Garnett and Bruggeman theories for gold particles in a surrounding
      matrix. It is found that both of these methods fail to predict the observed
      behavior for the film considered. 

PMID- 25607138
TI  - Additional waves in the graphene layered medium.
AB  - We investigate the features of additional waves that arise in the graphene
      layered medium, within the framework of nonlocal effective medium model. The
      additional wave is manifest on the biquadratic dispersion relation of the medium
      and represents as a distinctive nonlocal character at long wavelength. In
      particular, the reflection and transmission coefficients for the nonlocal medium
      are underdetermined by Maxwell's boundary conditions. An additional boundary
      condition based on modal expansions is proposed to derive the generalized Fresnel
      equations, based on which the additional wave in the graphene layered medium is
      determined. The additional wave tends to be significant near the effective plasma
      frequency, near which the graphene plasmons are excited inside the medium. 

PMID- 25607139
TI  - Computational approaches for generating electromagnetic Gaussian Schell-model
      sources.
AB  - Two different methodologies for generating an electromagnetic Gaussian-Schell
      model source are discussed. One approach uses a sequence of random phase screens
      at the source plane and the other uses a sequence of random complex transmittance
      screens. The relationships between the screen parameters and the desired
      electromagnetic Gaussian-Schell model source parameters are derived. The
      approaches are verified by comparing numerical simulation results with published
      theory. This work enables one to design an electromagnetic Gaussian-Schell model
      source with pre-defined characteristics for wave optics simulations or laboratory
      experiments. 

PMID- 25607140
TI  - Panoramic monocentric imaging using fiber-coupled focal planes.
AB  - Monocentric lenses provide high-resolution wide field of view imaging onto a
      hemispherical image surface, which can be coupled to conventional focal planes
      using fiber-bundle image transfer. We show the design and characterization of a 2
      glass concentric F/1.0 lens, and describe integration of 5 Mpixel 1.75um pitch
      back-side illuminated color CMOS sensors with 2.5um pitch fiber bundles, then
      show the fiber-coupled lens compares favorably in both resolution and light
      collection to a 10x larger conventional F/4 wide angle photographic lens. We
      describe assembly of the monocentric lens and 6 adjacent sensors with focus
      optomechanics into an extremely compact 30Mpixel panoramic imager with a 126
      degrees  "letterbox" format field of view. 

PMID- 25607141
TI  - Emission properties and CW laser operation of Pr:YLF in the 910 nm spectral
      range.
AB  - The polarized emission spectra for the <sup>3</sup>P<sub>0</sub>
      ><sup>1</sup>G<sub>4</sub> emission transition of the Pr<sup>3+</sup> ion around
      910 nm in the Pr<sup>3+</sup>:LiYF<sub>4</sub> (Pr:YLF) laser crystal were
      registered and calibrated in unit of cross sections for the first time.
      Continuous-wave (CW) laser operation is demonstrated at 915 nm in pi polarization
      by pumping the crystal with an optically pumped semiconductor laser (OPSL) at
      479.2 nm. An output power of 218 mW is thus obtained with a laser slope
      efficiency of about 24% for an output coupler (OC) transmission of 1.9%. CW laser
      operation is also demonstrated at 907 nm in sigma polarization by using a thin
      plate oriented at Brewster angle. An output power of about 89 mW with a slope
      efficiency of about 10% is then obtained for an OC transmission of 0.8%.The round
      trip cavity losses are estimated for different experimental cavity configurations
      to be about 1% and the typical beam quality M<sup>2</sup> factors measured in the
      transverse x and y directions are found equal to about 1.07 and 1.04,
      respectively. Finally, we also report on a double laser wavelength operation by
      using an OC with a transmission of about 0.05%, such effect resulting from joint
      etalon effects inside the cavity. 

PMID- 25607142
TI  - Cascaded phase-preserving multilevel amplitude regeneration.
AB  - The performance of cascaded in-line phase-preserving amplitude regeneration using
      nonlinear amplifying loop mirrors has been studied in numerical simulations. As
      an example of a spectrally efficient modulation format with two amplitude states
      and multiple phase states, the regeneration performance of a star-16QAM format,
      basically an 8PSK format with two amplitude levels, was evaluated. An increased
      robustness against amplified spontaneous emission and nonlinear phase noise was
      observed resulting in a significantly increased transmission distance. 

PMID- 25607143
TI  - A dual-polarization coherent communication system with simplified optical
      receiver for UDWDM-PON architecture.
AB  - A dual-polarization coherent heterodyne optical communication system using a
      simplified and low-cost demodulation scheme, for high-capacity UDWDM-PON access
      networks, is proposed and demonstrated. In this scheme, the signal light and
      reference light occupying each of the polarization modes are emitted
      simultaneously from the transmitter. The random phase fluctuations between the
      signal light and reference light are obviated completely by means of the
      application of the phase-correlated orthogonal lights. When the signal light in
      the each polarization mode is modulated with M-amplitude-shift keying (M-ASK) or
      M<sup>2</sup>-quadrature amplitude modulation (M<sup>2</sup>-QAM), the phase
      stable intermediate frequency (IF) signal with M-ASK or M<sup>2</sup>-QAM
      modulation in the corresponding polarization mode is available for conversion in
      the electrical domain by beating the modulated signal light with the un-modulated
      reference light. A new IF signal with M<sup>2</sup> or M<sup>4</sup>-QAM can be
      synthesized by the IF signals in both modes as long as the power ratio and time
      delay between the two-modes optical signals are set at the proper values. This is
      achieved without using polarization demultiplexing and complicated algorithms and
      the synthesized IF signal can be received and demodulated directly. A proof-of
      concept transmission link with dual-polarization 2-ASK is demonstrated. The
      experimental results are consistent with theoretical predictions. 

PMID- 25607144
TI  - Microscopic OCT imaging with focus extension by ultrahigh-speed acousto-optic
      tunable lens and stroboscopic illumination.
AB  - We develop high-resolution optical coherence tomography (OCT) system with high
      speed acousto-optic tunable lens. Stroboscopic pulsed illumination is used for
      the first time to perform time-resolved OCT imaging with acousto-optic tunable
      focusing. The operation of ultrahigh-speed tunable acousto-optic lens is
      demonstrated theoretically and experimentally. Focal position tuning at MHz
      frequency range is experimentally shown in the imaging system leading to OCT
      images with extended depth of focus. Imaging with active optical elements is
      helpful for improvement of photon collection efficiency, depth of focus and
      enhancement of the image quality. 

PMID- 25607145
TI  - Trans-oceanic class ultra-long-haul transmission using multi-core fiber.
AB  - Space-division multiplexing with uncoupled multi-core fiber is a promising
      technology to drastically increase a fiber capacity in optical communication
      systems. Trans-oceanic class ultra-long-haul transmission was successfully
      achieved by using 7-core MCF with suppressed inter-core crosstalk. By using a
      combination of MCF and spectral efficient modulation format, the fiber capacity
      could be increased from 28.8 Tbit/s to 140 Tbit/s and a capacity-distance product
      exceeding 1 Exabit/s.km was obtained in 7 cores x 201 lambda x 100 Gbit/s
      transmission over 7326 km. These results indicate that the MCF transmission will
      be one of promising candidates for future ultra-high capacity optical
      communication systems. 

PMID- 25607146
TI  - Polarization-insensitive all-optical dual pump-phase transmultiplexing from 2 *
      10-GBd OOKs to 10-GBd RZ-QPSK using cross-phase modulation in a birefringent
      nonlinear PCF.
AB  - Polarization-insensitive (PI) all-optical dual pump-phase transmultiplexing from
      2 * 10-GBd OOKs to 10-GBd RZ-QPSK was successfully demonstrated in a birefringent
      nonlinear photonic crystal fiber (PCF), by utilizing cross-phase modulation (XPM)
      and the inherent birefringence of the device, for the first time. PI operation
      was achieved by launching the probe and one pump off-axis while the state of
      polarization (SOP) of the other pump was randomized. Optimum pump-probe detuning,
      all within the C-Band, was also utilized to reduce the polarization-induced power
      fluctuation. Receiver sensitivity penalty at 10<sup>-9</sup> bit-error-rate was <
      5.5 dB in PI operation, relative to the FPGA-precoded RZ-DQPSK baseline. 

PMID- 25607147
TI  - Characterisation of the n-colour printing process using the spot colour overprint
      model.
AB  - This paper is aimed at reproducing the solid spot colours using the n-colour
      separation. A simplified numerical method, called as the spot colour overprint
      (SCOP) model, was used for characterising the n-colour printing process. This
      model was originally developed for estimating the spot colour overprints. It was
      extended to be used as a generic forward characterisation model for the n-colour
      printing process. The inverse printer model based on the look-up table was
      implemented to obtain the colour separation for n-colour printing process.
      Finally the real-world spot colours were reproduced using 7-colour separation on
      lithographic offset printing process. The colours printed with 7 inks were
      compared against the original spot colours to evaluate the accuracy. The results
      show good accuracy with the mean CIEDE2000 value between the target colours and
      the printed colours of 2.06. The proposed method can be used successfully to
      reproduce the spot colours, which can potentially save significant time and cost
      in the printing and packaging industry. 

PMID- 25607148
TI  - Integrated optical dual-cantilever arrays in silica on silicon.
AB  - A dual cantilever device has been demonstrated which can operate as a force
      sensor or variable attenuator. The device is fabricated using physical
      micromachining techniques that do not require cleanroom class facilities. The
      response of the device to mechanical actuation is measured, and shown to be well
      described by conventional fiber optic angular misalignment theory. The device has
      the potential to be utilized within integrated optical components for sensors or
      attenuators. An array of devices was fabricated with potential for parallel
      operation. 

PMID- 25607149
TI  - Simplified method for numerical modeling of fiber lasers.
AB  - A simplified numerical approach to modeling of dissipative dispersion-managed
      fiber lasers is examined. We present a new numerical iteration algorithm for
      finding the periodic solutions of the system of nonlinear ordinary differential
      equations describing the intra-cavity dynamics of the dissipative soliton
      characteristics in dispersion-managed fiber lasers. We demonstrate that results
      obtained using simplified model are in good agreement with full numerical
      modeling based on the corresponding partial differential equations. 

PMID- 25607150
TI  - Telecentric 3D profilometry based on phase-shifting fringe projection.
AB  - Three dimensional shape measurement in the microscopic range becomes increasingly
      important with the development of micro manufacturing technology. Microscopic
      fringe projection techniques offer a fast, robust, and full-field measurement for
      field sizes from approximately 1 mm<sup>2</sup> to several cm<sup>2</sup>.
      However, the depth of field is very small due to the imaging of non-telecentric
      microscope, which is often not sufficient to measure the complete depth of a 3D
      object. And the calibration of phase-to-depth conversion is complicated which
      need a precision translation stage and a reference plane. In this paper, we
      propose a novel telecentric phase-shifting projected fringe profilometry for
      small and thick objects. Telecentric imaging extends the depth of field
      approximately to millimeter order, which is much larger than that of microscopy.
      To avoid the complicated phase-to-depth conversion in microscopic fringe
      projection, we develop a new system calibration method of camera and projector
      based on telecentric imaging model. Based on these, a 3D reconstruction of
      telecentric imaging is presented with stereovision aided by fringe phase maps.
      Experiments demonstrated the feasibility and high measurement accuracy of the
      proposed system for thick object. 

PMID- 25607151
TI  - Optical limiting properties and mechanisms of single-layer graphene dispersions
      in heavy-atom solvents.
AB  - The optical limiting (OL) properties of single-layer graphene dispersions in
      different solvents were studied using a nanosecond pulse laser. The graphene
      dispersions, especially in heavy-atom solvents, showed much better OL properties
      compared with referenced C<sub>60</sub>-toluene solution. The dependences of OL
      thresholds and nonlinear scattering (NLS) intensities on the solvent surface
      tensions indicated that, NLS effect played an important role in the OL process of
      graphene dispersions, while nonlinear absorption (NLA) effect might also
      contribute in solvents with heavy atoms. The NLA measurements further
      demonstrated the contribution of NLA effect to the excellent OL property of
      graphene dispersions in heavy-atom solvents. 

PMID- 25607152
TI  - Variational and accessible soliton approximations to multidimensional solitons in
      highly nonlocal nonlinear media.
AB  - We apply the variational approach to solitons in highly nonlocal nonlinear media
      in D = 1, 2, 3 dimensions. We compare results obtained by the variational
      approach with those obtained by the accessible soliton approximation, by
      considering the same system of equations in the same spatial region and under the
      same boundary conditions. To assess the accuracy of these approximations, we also
      compare them with the numerical solution of the equations. We discover that the
      accessible soliton approximation suffers from systematic errors, when compared to
      the variational approach and the numerical solution. The errors increase with the
      dimension of the system. The variational highly nonlocal approximation provides
      more accurate results in any dimension and as such is more appropriate solution
      than the accessible soliton approximation. 

PMID- 25607153
TI  - Enhanced field-of-view integral imaging display using multi-Kohler illumination.
AB  - A common drawback in 3D integral imaging displays is the appearance of
      pseudoimages beyond the viewing angle. These pseudoimages appear when the light
      rays coming from each elemental image are not passing through the corresponding
      microlens, and a set of barriers must be used to avoid this flipping effect. We
      present a pure optical arrangement based on Kohler illumination to generate these
      barriers thus avoiding the pseudoimages. The proposed system does not use
      additional lenses to project the elemental images, so no optical aberrations are
      introduced. As an added benefit, Kohler illumination provides a higher contrast
      3D display. 

PMID- 25607154
TI  - Performance analysis of a mirror by numerical iterative method.
AB  - Zernike polynomials are generally used to predict the optical performance of a
      mirror. However, it can also be done by a numerical iterative method. As piston,
      tip, tilt, and defocus (P.T.T.F) aberrations can be easily removed by optical
      alignment, we iteratively used a rotation transformation and a paraboloid graph
      subtraction for removal of the aberrations from a raw deformation of the optical
      surface through a Finite Element Method (FEM). The results of a 30 cm concave
      circular mirror corrected by the iterative method were almost the same as those
      yielded by Zernike polynomial fitting, and the computational time was fast. In
      addition, a concave square mirror whose surface area is pi was analyzed in order
      to visualize the deformation maps of a general mirror aperture shape. The
      iterative method can be applicable efficiently because it does not depend on the
      mirror aperture shape. 

PMID- 25607155
TI  - Epsilon-near-zero meta-lens for high resolution wide-field imaging.
AB  - Herein, we will propose a new application possibility of epsilon-near-zero (ENZ)
      materials: high resolution wide-field imaging. We show that the resolution can be
      dramatically enhanced by simply inserting a thin epsilon-near-zero (ENZ) material
      between the sample and substrate. By performing metal half-plane imaging, we
      experimentally demonstrate that the resolution could be enhanced by about 47%
      with a 300-nm-thick SiO<sub>2</sub> interlayer, an ENZ material at 8-MUm
      wavelength (1250 cm<sup>-1</sup>). The physical origin of the resolution
      enhancement is the strong conversion of diffracted near fields to quasi-zeroth
      order far fields enabled by the directive emission of ENZ materials. 

PMID- 25607156
TI  - Hybrid Brillouin/thulium multiwavelength fiber laser with switchable single- and
      double-Brillouin-frequency spacing.
AB  - We demonstrate a multiwavelength laser at 2 um based on a hybrid gain scheme
      consisting of a Brillouin gain medium and a thulium-doped fiber. The laser has
      switchable frequency spacing, corresponding to the single and double Brillouin
      frequency shifts. In the 20 dB bandwidth, seven lasing channels with a frequency
      spacing of 0.1 nm (7.62 GHz) and eleven channels with a double-spacing of 0.2 nm
      (15.24 GHz) are obtained. A wavelength tunability of 1.3 nm is realized for both
      laser configurations by shifting the pump wavelength. Strong four wave mixing is
      observed in the double-spacing laser resulting in an improved performance: larger
      number of channels and better temporal stability. 

PMID- 25607157
TI  - Theoretical study of polarization insensitivity of carrier-induced refractive
      index change of multiple quantum well.
AB  - Characteristics of polarization insensitivity of carrier-induced refractive index
      change of 1.55 MUm tensile-strained multiple quantum well (MQW) are theoretically
      investigated. A comprehensive MQW model is proposed to effectively extend the
      application range of previous models. The model considers the temperature
      variation as well as the nonuniform distribution of injected carrier in MQW.
      Tensile-strained MQW is expected to achieve polarization insensitivity of carrier
      induced refractive index change over a wide wavelength range as temperature
      varies from 0 degrees C to 40 degrees C, while the magnitude of refractive index
      change keeps a large value (more than 3 * 10<sup>-3</sup>). And that the
      polarization insensitivity of refractive index change can maintain for a wide
      range of carrier concentration. Multiple quantum well with different material and
      structure parameters is anticipated to have the similar polarization
      insensitivity of refractive index change, which shows the design flexibility. 

PMID- 25607158
TI  - Low-crosstalk Si arrayed waveguide grating with parabolic tapers.
AB  - A silicon arrayed waveguide grating (AWG) with low channel crosstalk was
      demonstrated by using ultra-short parabolic tapers to connect the AWG's free
      propagation regions and single-mode waveguides. The tapers satisfied the
      requirements of low-loss mode conversion and lower channel crosstalk from the
      coupling of neighboring waveguides in the AWGs. In this work, three different
      tapers, including parabolic tapers, linear tapers, and exponential tapers, were
      theoretically analyzed and experimentally investigated for a comparison of their
      effects when implemented in AWGs. The experimental results showed that the AWG
      with parabolic tapers had a crosstalk improvement up to 7.1 dB compared with the
      others. Based on the advantages of parabolic tapers, a 400-GHz 8 * 8 cyclic AWG
      with 2.4 dB on-chip loss and -17.6~-25.1 dB crosstalk was fabricated using a
      simple one-step etching process. Its performance was comparable with that of
      existing AWGs with bi-level tapers, which require complicated two-step etching
      fabrication processes. 

PMID- 25607159
TI  - Surface antireflection properties of GaN nanostructures with various effective
      refractive index profiles.
AB  - GaN nanostructures with various effective refractive index profiles (Linear,
      Cubic, and Quintic functions) were numerically studied as broadband
      omnidirectional antireflection structures for concentrator photovoltaics by using
      three-dimensional finite difference time domain (3D-FDTD) method. Effective
      medium theory was used to design the surface structures corresponding to
      different refractive index profiles. Surface antireflection properties were
      calculated and analyzed for incident light with wavelength, polarization and
      angle dependences. The surface antireflection properties of GaN nanostructures
      based on six-sided pyramid with both uniform and non-uniform patterns were also
      investigated. Results indicate a significant dependence of the surface
      antireflection on the refractive index profiles of surface nanostructures as well
      as their pattern uniformity. The GaN nanostructures with linear refractive index
      profile show the best performance to be used as broadband omnidirectional
      antireflection structures. 

PMID- 25607160
TI  - Etching Bragg gratings in Panda fibers for the temperature-independent refractive
      index sensing.
AB  - We demonstrate the evolution of the Bragg gratings inscribed in Panda fibers with
      chemical etching. The resonance wavelengths can blueshift with cladding reduction
      similar to the conventional counterparts. But the wavelength separation between
      the two polarizations is co-determined by the stress and the asymmetric shape
      effects. The fast and slow axes of the fiber can be reversed with each other and
      zero birefringence can be achieved by chemical etching the structure. When the
      stress-applying parts of the fiber are removed, the finalizing grating can be
      exploited for the temperature-independent refractive index sensing, since the
      modes corresponding to the two polarizations exhibit the dissimilar responses to
      the external refractive index change but the same response to temperature. Our
      device is featured with easy achievement, spectral controllability, and relative
      robustness. 

PMID- 25607161
TI  - Stereoscopic 3D display with color interlacing improves perceived depth.
AB  - Temporal interlacing is a method for presenting stereoscopic 3D content whereby
      the two eyes' views are presented at different times and optical filtering
      selectively delivers the appropriate view to each eye. This approach is prone to
      distortions in perceived depth because the visual system can interpret the
      temporal delay between binocular views as spatial disparity. We propose a novel
      color-interlacing display protocol that reverses the order of binocular
      presentation for the green primary but maintains the order for the red and blue
      primaries: During the first sub-frame, the left eye sees the green component of
      the left-eye view and the right eye sees the red and blue components of the right
      eye view, and vice versa during the second sub-frame. The proposed method
      distributes the luminance of each eye's view more evenly over time. Because
      disparity estimation is based primarily on luminance information, a more even
      distribution of luminance over time should reduce depth distortion. We conducted
      a psychophysical experiment to test these expectations and indeed found that less
      depth distortion occurs with color interlacing than temporal interlacing. 

PMID- 25607162
TI  - High resolution integral holography using Fourier ptychographic approach.
AB  - An innovative approach is proposed for calculating high resolution computer
      generated integral holograms by using the Fourier Ptychographic (FP) algorithm.
      The approach initializes a high resolution complex hologram with a random guess,
      and then stitches together low resolution multi-view images, synthesized from the
      elemental images captured by integral imaging (II), to recover the high
      resolution hologram through an iterative retrieval with FP constrains. This paper
      begins with an analysis of the principle of hologram synthesis from multi
      projections, followed by an accurate determination of the constrains required in
      the Fourier ptychographic integral-holography (FPIH). Next, the procedure of the
      approach is described in detail. Finally, optical reconstructions are performed
      and the results are demonstrated. Theoretical analysis and experiments show that
      our proposed approach can reconstruct 3D scenes with high resolution. 

PMID- 25607163
TI  - Evaluation of path-history-based fluorescence Monte Carlo method for photon
      migration in heterogeneous media.
AB  - The path-history-based fluorescence Monte Carlo method used for fluorescence
      tomography imaging reconstruction has attracted increasing attention. In this
      paper, we first validate the standard fluorescence Monte Carlo (sfMC) method by
      experimenting with a cylindrical phantom. Then, we describe a path-history-based
      decoupled fluorescence Monte Carlo (dfMC) method, analyze different perturbation
      fluorescence Monte Carlo (pfMC) methods, and compare the calculation accuracy and
      computational efficiency of the dfMC and pfMC methods using the sfMC method as a
      reference. The results show that the dfMC method is more accurate and efficient
      than the pfMC method in heterogeneous medium. 

PMID- 25607164
TI  - Experimental and numerical evaluation of inter-core differential mode delay
      characteristic of weakly-coupled multi-core fiber.
AB  - We investigated the inter-core differential mode delay (DMD) characteristic of a
      weakly-coupled homogeneous multi-core fiber with a view to utilizing inter-core
      crosstalk compensation with MIMO processing. We confirmed experimentally that the
      bend induced inter-core DMD is lower than the simulated results, which we
      expected owing to the twist of the fiber. We also revealed numerically that the
      refractive index profile variation of each core greatly increases inter-core DMD.
      Finally, we conducted a 4 * 4 MIMO transmission experiment using a weakly-coupled
      4-core fiber and successfully compensated for the inter-core crosstalk. 

PMID- 25607165
TI  - An ultra-low detection-limit optofluidic biosensor based on all glass Fabry-Perot
      cavity.
AB  - An all glass optofludic biosensor with high quality-factor Fabry-Perot cavity
      (FPC) channel was reported. The all glass sandwich structure can completely
      eliminate the etching roughness of the channel surface, and can extend the
      operating wavelength to visible and ultraviolet regions compared with that of Si
      based sensor. The quality-factor of the FPC channel is 875, and the system noise
      can be reduced to 1.2 nV by combining optical differential detection with phase
      lock-in detection. A detection limit of 15ng/mL for glucose solution, which
      corresponds to a refractive index unit of 2.0 * 10<sup>-9</sup>, was
      experimentally demonstrated. The all glass FPC sensor features low cost and
      robust compared with surface-plasmon-resonance sensor and ring-resonator sensor. 

PMID- 25607166
TI  - Optical fiber axial micro-displacement sensor based on Mach-Zehnder
      interferometer.
AB  - A Mach-Zehnder interferometer (MZI) based fiber axial micro-displacement sensor
      was proposed. The MZI was constructed by a bowknot-type taper (BTT) combining
      with a fiber core-offset between two single mode fibers (SMFs). The axial micro
      displacement of the core offset is correlated with the MZI transmission spectrum
      and varied with the interferometer arm length. For the arm length L of 12, 18, 24
      and 30 mm, the proposed sensors showed high sensitivity of -0.362 dB/MUm, -0.385
      dB/MUm, -0.332 dB/MUm and -0.235dB/MUm, and temperature errors of -0.056 dB/
      degrees C, -0.036 dB/ degrees C, -0.044 dB/ degrees C, -0.048 dB/ degrees C,
      respectively. The theoretical simulations of the energy distributions were also
      given. The obtained sensitivity of -0.385 dB/MUm is about 150 times high than
      that of the current similar existing axial micro-displacement sensor. 

PMID- 25607167
TI  - Integrated programmable photonic filter on the silicon-on-insulator platform.
AB  - We propose and demonstrate a silicon-on-insulator (SOI) on-chip programmable
      filter based on a four-tap finite impulse response structure. The photonic filter
      is programmable thanks to amplitude and phase modulation of each tap controlled
      by thermal heaters. We further demonstrate the tunability of the filter central
      wavelength, bandwidth and variable passband shape. The tuning range of the
      central wavelength is at least 42% of the free spectral range. The bandwidth
      tuning range is at least half of the free spectral range. Our scheme has distinct
      advantages of compactness, capability for integrating with electronics. 

PMID- 25607168
TI  - Spin scan tomographic array-based imager.
AB  - This work presents a novel imaging device based on tomographic reconstruction.
      Similar in certain aspects to the earlier presented tomographic scanning (TOSCA)
      principle, it provides several important enhancements. The device described
      generates a stream of one-dimensional projections from a linear array of thin
      stripe detectors onto which the (circular) image of the scene is rotated. A two
      dimensional image is then reproduced from the one-dimensional signals using
      tomographic processing techniques. A demonstrator is presented. Various aspects
      of the design and construction are discussed, and resulting images and movies are
      presented. 

PMID- 25607169
TI  - Temporal reshaping of two-dimensional pulses.
AB  - An analytic study of complete cylindrical focusing of pulses in two dimensions is
      presented, and compared with the analogous three-dimensional case of focusing
      over a complete sphere. Such behavior is relevant for understanding the limiting
      performance of ultrafast, planar photonic and plasmonic devices. A particular
      spectral distribution is assumed that contains finite energy. Separate ingoing
      and outgoing pulsed waves are considered, along with the combination that would
      be generated in free space by an ingoing wave. It is shown that for the two
      dimensional case, in order to produce a temporally symmetrical pulse at the
      focus, an asymmetric pulse must be launched. A symmetrical outgoing pulse is
      generated from a source with asymmetric time behavior, or an anti-symmetric input
      pulse. These results are very different from the corresponding three-dimensional
      case, and imply fundamental limitations on the performance of ultrafast, tightly
      focused, two-dimensional devices. 

PMID- 25607170
TI  - Plasmonic amplification for bioassays with epi-fluorescence readout.
AB  - Corrugated metallic surfaces offer means for efficient amplification of
      fluorescence bioassay signal based on the near field coupling between surface
      plasmons and fluorophore emitters that are used as labels. This paper discusses
      the design of such plasmonic structure to enhance the sensitivity of immunoassays
      with epi-fluorescence readout geometry. In particular, crossed gold grating is
      theoretically and experimentally investigated for combined increasing of the
      excitation rate at the fluorophore excitation wavelength and utilizing
      directional surface plasmon-coupled fluorescence emission. For Alexa Fluor 647
      dye, the enhancement factor of around EF = 10<sup>2</sup> was simulated and
      experimentally measured. When applied to a sandwich interleukin-6 immunoassay,
      highly surface-selective enhancement reaching a similar value was observed.
      Besides increasing the measured fluorescence signal associated with the molecular
      binding events on a surface by two orders of magnitude, the presented approach
      enables measuring kinetics of the surface reaction that is otherwise masked by
      strong background signal originating from bulk solution. 

PMID- 25607171
TI  - Theory of intermodal four-wave mixing with random linear mode coupling in few
      mode fibers.
AB  - We study intermodal four-wave mixing (FWM) in few-mode fibers in the presence of
      birefringence fluctuations and random linear mode coupling. Two different
      intermodal FWM processes are investigated by including all nonlinear
      contributions to the phase-matching condition and FWM bandwidth. We find that one
      of the FWM processes has a much larger bandwidth than the other. We include
      random linear mode coupling among fiber modes using three different models based
      on an analysis of the impact of random coupling on differences of propagation
      constants between modes. We find that random coupling always reduces the FWM
      efficiency relative to its vale in the absence of linear coupling. The reduction
      factor is relatively small (about 3 dB) when only a few modes are linearly
      coupled but can become very large (> 40 dB) when all modes couple strongly. In
      the limit of a coupling length much shorter than the nonlinear length, intermodal
      FWM efficiency becomes vanishingly small. These results should prove useful in
      the context of space-division multiplexing with few-mode and multimode fibers. 

PMID- 25607172
TI  - Mode conversion based on forward stimulated Brillouin scattering in a hybrid
      phononic-photonic waveguide.
AB  - We propose a scheme for on-chip all optical mode conversion based on forward
      stimulated Brillouin scattering in a hybrid phononic-photonic waveguide. To
      describe the mode conversion the theoretical model of the FSBS is established by
      taking into account the radiation pressure and the electrostriction force
      simultaneously. The numerical simulation is carried out for the mode conversion
      from the fundamental mode E11x to the higher-order mode E21x. The results
      indicate that the mode conversion efficiency is affected by the waveguide length
      and the input pump light power, and the highest efficiency can reach upto 88% by
      considering the influence of optical and acoustic absorption losses in the hybrid
      waveguide. Additionally, the conversion bandwidth with approximate 12.5 THz can
      be achieved in 1550nm communication band. This mode converter on-chip is a
      promising device in the integrated optical systems, which can effectively
      increase the capacity of silicon data busses for on-chip optical
      interconnections. 

PMID- 25607173
TI  - Nanofocusing of terahertz wave in a tapered hyperbolic metal waveguide.
AB  - An tapered hyperbolic metal waveguide is suggested for the nanofocusing of
      terahertz waves. We numerically show that, at the frequency of 1 THz, the focal
      spot can be as small as only 5 nm, which is smaller than that of a plate
      waveguide by 2 orders of magnitude. Correspondingly, the longitudinal component
      of the energy flow density is stronger than that of a plate waveguide by 3 orders
      of magnitude for the same input. It is shown that these significant improvements
      come from the small imaginary part of the effective index of the hyperbolic metal
      waveguide. 

PMID- 25607174
TI  - Parallel ptychographic reconstruction.
AB  - Ptychography is an imaging method whereby a coherent beam is scanned across an
      object, and an image is obtained by iterative phasing of the set of diffraction
      patterns. It is able to be used to image extended objects at a resolution limited
      by scattering strength of the object and detector geometry, rather than at an
      optics-imposed limit. As technical advances allow larger fields to be imaged,
      computational challenges arise for reconstructing the correspondingly larger data
      volumes, yet at the same time there is also a need to deliver reconstructed
      images immediately so that one can evaluate the next steps to take in an
      experiment. Here we present a parallel method for real-time ptychographic phase
      retrieval. It uses a hybrid parallel strategy to divide the computation between
      multiple graphics processing units (GPUs) and then employs novel techniques to
      merge sub-datasets into a single complex phase and amplitude image. Results are
      shown on a simulated specimen and a real dataset from an X-ray experiment
      conducted at a synchrotron light source. 

PMID- 25607175
TI  - Generation of bright attosecond x-ray pulse trains via Thomson scattering from
      laser-plasma accelerators.
AB  - Generation of attosecond x-ray pulse attracts more and more attention within the
      advanced light source user community due to its potentially wide applications.
      Here we propose an all-optical scheme to generate bright, attosecond hard x-ray
      pulse trains by Thomson backscattering of similarly structured electron beams
      produced in a vacuum channel by a tightly focused laser pulse. Design parameters
      for a proof-of-concept experiment are presented and demonstrated by using a
      particle-in-cell code and a four-dimensional laser-Compton scattering simulation
      code to model both the laser-based electron acceleration and Thomson scattering
      processes. Trains of 200 attosecond duration hard x-ray pulses holding stable
      longitudinal spacing with photon energies approaching 50 keV and maximum
      achievable peak brightness up to 10<sup>20</sup>
      photons/s/mm<sup>2</sup>/mrad<sup>2</sup>/0.1%BW for each micro-bunch are
      observed. The suggested physical scheme for attosecond x-ray pulse trains
      generation may directly access the fastest time scales relevant to electron
      dynamics in atoms, molecules and materials. 

PMID- 25607176
TI  - Regularized iterative integration combined with non-linear diffusion filtering
      for phase-contrast x-ray computed tomography.
AB  - Phase-contrast x-ray computed tomography has a high potential to become
      clinically implemented because of its complementarity to conventional absorption
      contrast.In this study, we investigate noise-reducing but resolution-preserving
      analytical reconstruction methods to improve differential phase-contrast imaging.
      We apply the non-linear Perona-Malik filter on phase-contrast data prior or post
      filtered backprojected reconstruction. Secondly, the Hilbert kernel is replaced
      by regularized iterative integration followed by ramp filtered backprojection as
      used for absorption-contrast imaging. Combining the Perona-Malik filter with this
      integration algorithm allows to successfully reveal relevant sample features,
      quantitatively confirmed by significantly increased structural similarity indices
      and contrast-to-noise ratios. With this concept, phase-contrast imaging can be
      performed at considerably lower dose. 

PMID- 25607177
TI  - Imaging bacterial 3D motion using digital in-line holographic microscopy and
      correlation-based de-noising algorithm.
AB  - Better understanding of bacteria environment interactions in the context of
      biofilm formation requires accurate 3-dimentional measurements of bacteria
      motility. Digital Holographic Microscopy (DHM) has demonstrated its capability in
      resolving 3D distribution and mobility of particulates in a dense suspension. Due
      to their low scattering efficiency, bacteria are substantially difficult to be
      imaged by DHM. In this paper, we introduce a novel correlation-based de-noising
      algorithm to remove the background noise and enhance the quality of the hologram.
      Implemented in conjunction with DHM, we demonstrate that the method allows DHM to
      resolve 3-D E. coli bacteria locations of a dense suspension (>10<sup>7</sup>
      cells/ml) with submicron resolutions (<0.5 um) over substantial depth and to
      obtain thousands of 3D cell trajectories. 

PMID- 25607178
TI  - Experimental demonstration and devices optimization of NRZ-DPSK amplitude
      regeneration scheme based on SOAs.
AB  - We propose and experimentally demonstrate a novel scheme which can simultaneously
      realize wavelength-preserving and phase-preserving amplitude noise compression of
      a 40 Gb/s distorted non-return-to-zero differential-phase-shift keying (NRZ-DPSK)
      signal. In the scheme, two semiconductor optical amplifiers (SOAs) are exploited.
      The first one (SOA1) is used to generate the inverted signal based on SOA's
      transient cross-phase modulation (T-XPM) effect and the second one (SOA2) to
      regenerate the distorted NRZ-DPSK signal using SOA's cross-gain compression (XGC)
      effect. In the experiment, the bit error ratio (BER) measurements show that power
      penalties of constructive and destructive demodulation at BER of 10<sup>-9</sup>
      are -1.75 and -1.01 dB, respectively. As the nonlinear effects and the
      requirements of the two SOAs are completely different, quantum-well (QW)
      structures has been separately optimized. A complicated theoretical model by
      combining QW band structure calculation with SOA's dynamic model is exploited to
      optimize the SOAs, in which both interband effect (carrier density variation) and
      intraband effect (carrier temperature variation) are taken into account.
      Regarding SOA1, we choose the tensile strained QW structure and large optical
      confinement factor to enhance the T-XPM effect. Regarding SOA2, the compressively
      strained QW structure is selected to reduce the impact of excess phase noise
      induced by amplitude fluctuations. Exploiting the optimized QW SOAs, better
      amplitude regeneration performance is demonstrated successfully through numerical
      simulation. The proposed scheme is intrinsically stable comparing with the
      interferometer structure and can be integrated on a chip, making it a practical
      candidate for all-optical amplitude regeneration of high-speed NRZ-DPSK signal. 

PMID- 25607179
TI  - Planarised optical fiber composite using flame hydrolysis deposition
      demonstrating an integrated FBG anemometer.
AB  - This paper reports for the first time a planarised optical fiber composite formed
      using Flame Hydrolysis Deposition (FHD). As a way of format demonstration a Micro
      Opto-Electro-Mechanical (MOEMS) hot wire anemometer is formed using micro
      fabrication processing. The planarised device is rigidly secured to a silicon
      wafer using optical quality doped silica that has been deposited using flame
      hydrolysis and consolidated at high temperature. The resulting structure can
      withstand temperatures exceeding 580K and is sensitive enough to resolve free and
      forced convection interactions at low fluid velocity. 

PMID- 25607180
TI  - Phase noise performance comparison between optoelectronic oscillators based on
      optical delay lines and whispering gallery mode resonators.
AB  - We investigate the phase noise performance of optoelectronic oscillators when the
      optical energy storage elements are in the following three configurations: a high
      Q whispering gallery mode resonator, an optical delay-line and a combination of
      both elements. The stability properties of these various optical elements are
      first characterized, and then systematically compared in the optical and in the
      microwave frequency domains. Subsequently, the spectral purity of the oscillator
      is theoretically and experimentally examined for each case. When the resonator is
      used as both delay and filtering element inside the delay-line based oscillator,
      the generated spurious modes are highly rejected. A spur rejection by more than
      53 dB has been demonstrated for the first-neighboring spur. 

PMID- 25607181
TI  - Design and production of antireflection coating for the 8-10 um spectral region.
AB  - A special design procedure allowing to trap layer thicknesses inside specified
      limits is applied for designing of antireflection coating (AR) for the infrared
      spectral band of 8-10 um. The obtained AR design has no too thick layers that may
      cause delaminating of the deposited AR coating. A special monitoring procedure
      taking into account wavelength positions of monitoring signal extrema is applied
      for coating deposition. The manufactured coating features excellent AR properties
      in the requested spectral region and possesses high mechanical stability. 

PMID- 25607182
TI  - Control of cavity lifetime of 1.5 um wafer-fused VCSELs by digital mirror
      trimming.
AB  - Digital chemical etching is used to trim the output mirror thickness of wafer
      fused VCSELs emitting at a wavelength near 1.5um. The fine control of the photon
      cavity lifetime thus achieved is employed to extract important device parameters
      and optimize the combination of the threshold current, output power, and direct
      current modulation characteristics. The fabrication process is compatible with
      industrial production and should help in improving device yield and in reducing
      manufacturing costs. 

PMID- 25607183
TI  - Optimal signal constellation design for ultra-high-speed optical transport in the
      presence of nonlinear phase noise.
AB  - In this paper, we first describe an optimal signal constellation design algorithm
      suitable for the coherent optical channels dominated by the linear phase noise.
      Then, we modify this algorithm to be suitable for the nonlinear phase noise
      dominated channels. In optimization procedure, the proposed algorithm uses the
      cumulative log-likelihood function instead of the Euclidian distance. Further, an
      LDPC coded modulation scheme is proposed to be used in combination with signal
      constellations obtained by proposed algorithm. Monte Carlo simulations indicate
      that the LDPC-coded modulation schemes employing the new constellation sets,
      obtained by our new signal constellation design algorithm, outperform
      corresponding QAM constellations significantly in terms of transmission distance
      and have better nonlinearity tolerance. 

PMID- 25607184
TI  - Errata: Frequency ratio measurement of <sup>171</sup>Yb and <sup>87</sup>Sr
      optical lattice clocks.
AB  - We correct the errors in the uncertainty budget. The determined ratio
      (nu<sub>Yb</sub>/nu<sub>Sr</sub>) is corrected to be 1.207 507 039 343 341 2(17)
      with a fractional standard uncertainty of 1.4 * 10<sup>-15</sup>. 

PMID- 25607185
TI  - Low thermal-mass LEDs: size effect and limits.
AB  - In this work, low thermal-mass LEDs (LTM-LEDs) were developed and demonstrated in
      flip-chip configuration, studying both experimentally and theoretically the
      enhanced electrical and optical characteristics and the limits. LTM-LED chips in
      25 * 25 MUm<sup>2</sup>, 50 * 50 MUm<sup>2</sup>, 100 * 100 MUm<sup>2</sup> and
      200 * 200 MUm<sup>2</sup> mesa sizes were fabricated and comparatively
      investigated. Here it was revealed that both the electrical and optical
      properties are improved by the decreasing chip size due to the reduced thermal
      mass. With a smaller chip size (from 200 MUm to 50 MUm), the device generally
      presents higher current density against the bias and higher power density against
      the current density. However, the 25 * 25 MUm<sup>2</sup> device behaves
      differently, limited by the fabrication margin limit of 10 MUm. The underneath
      mechanisms of these observations are uncovered, and furthermore, based on the
      device model, it is proven that for a specific flip-chip fabrication process, the
      ideal size for LTM-LEDs with optimal power density performance can be identified.

PMID- 25607186
TI  - Color sorting by retinal waveguides.
AB  - Light is being detected by the two distinct types of photoreceptors in the human
      retina: cones and rods. Before light arrives at the photoreceptors, it must
      traverse the whole retina, along its array of higher-index Muller cells serving
      as natural waveguides. Here we analyze this optical process of light propagation
      through Muller cells by two independent optical methods: numerical beam
      propagation and analytical modal analysis. We show that the structure and
      refractive index profile of the Muller cells create a unique spatio-spectral
      distribution of light. This distribution corresponds to the positions and
      spectral sensitivities of both cones and rods to improve their light absorption. 

PMID- 25607187
TI  - Pre-chirping management of a self-similar Yb-fiber amplifier towards 80 W average
      power with sub-40 fs pulse generation.
AB  - We report on the generation of 80-W average power 38-fs laser pulse from a 2-m
      polarization-maintaining large-mode-area photonic crystal fiber amplifier with
      high pump absorption coefficient. The pre-chirping management was demonstrated to
      play a key role on the self-similar amplification. The achieved spectral
      bandwidth and compressed pulse duration were determined by the interplay between
      self-phase modulation and finite gain bandwidth. The power scaling in the self
      similar fiber amplifier system was eventually limited by the onset of stimulated
      Raman scattering. 

PMID- 25607188
TI  - Improved geometrical model of fringe projection profilometry.
AB  - The accuracy performance of fringe projection profilometry (FPP) depends on
      accurate phase-to-height (PTH) mapping and system calibration. The existing PTH
      mapping is derived based on the condition that the plane formed by axes of camera
      and projector is perpendicular to the reference plane, and measurement error
      occurs when the condition is not met. In this paper, a new geometric model for
      FPP is presented to lift the condition, resulting in a new PTH mapping
      relationship. The new model involves seven parameters, and a new system
      calibration method is proposed to determine their values. Experiments are
      conducted to verify the performance of the proposed technique, showing a
      noticeable improvement in the accuracy of 3D shape measurement. 

PMID- 25607189
TI  - Enhanced broadband absorption in gold by plasmonic tapered coaxial holes.
AB  - Gold absorbers based on plasmonic tapered coaxial holes (PTCHs) are demonstrated
      theoretically and experimentally. An average absorption of over 0.93 is obtained
      theoretically in a broad wavelength range from 300 nm to 900 nm without
      polarization sensitivity due to the structural symmetry. Strong scattering of the
      incident light by the tapered coaxial holes is the main reason for the high
      absorption in the short wavelength range below about 550 nm, while gap surface
      plasmon polaritons propagating along the taper dominate the resonance-induced
      high absorption in the long wavelength range. Combining two PTCHs with different
      structural parameters can further enhance the absorption and thus increase the
      spectral bandwidth, which is verified by a sample fabricated by focused ion beam
      milling. This design is promising to be extended to other metals to realize
      effective and efficient light harvesting and absorption. 

PMID- 25607190
TI  - Miniature multi-contact MEMS switch for broadband terahertz modulation.
AB  - A miniature MEMS switch is designed, fabricated, and incorporated in a
      reconfigurable metallic mesh filter for broadband terahertz modulation. The
      mechanical, electrical, and geometrical properties of the MEMS switch are set to
      enable broadband terahertz modulation with relatively low modulation voltage,
      high modulation speed, and high device reliability. The implemented miniature
      MEMS switch exhibits an actuation voltage of 30 V, a fundamental mechanical
      resonance frequency of 272 kHz, and an actuation time of 1.23 MUs, enabling
      terahertz modulation with a record high modulation depth of more than 70% over a
      terahertz band of 0.1-1.5 THz, with a modulation voltage of 30 V and modulation
      speeds exceeding 20 kHz. 

PMID- 25607191
TI  - Laser-induced oxidation kinetics of bismuth surface microdroplets on GaAsBi
      studied in situ by Raman microprobe analysis.
AB  - We report the cw-laser-induced oxidation of molecular-beam-epitaxy grown GaAsBi
      bismuth surface microdroplets investigated in situ by micro-Raman spectroscopy
      under ambient conditions as a function of irradiation power and time. Our results
      reveal the surface droplets are high-purity crystalline bismuth and the resultant
      Bi<sub>2</sub>O<sub>3</sub> transformation to be beta-phase and stable at room
      temperature. A detailed Raman study of Bi microdroplet oxidation kinetics yields
      insights into the laser-induced oxidation process and offers useful real-time
      diagnostics. The temporal evolution of new beta-Bi<sub>2</sub>O<sub>3</sub> Raman
      modes is shown to be well described by Johnson-Mehl-Avrami-Kolmogorov kinetic
      transformation theory and while this study limits itself to the laser-induced
      oxidation of GaAsBi bismuth surface droplets, the results will find application
      within the wider context of bismuth laser-induced oxidation and direct Raman
      laser processing. 

PMID- 25607192
TI  - High-resolution terahertz spectroscopy with a single tunable frequency comb.
AB  - We report an improvement of three orders of magnitude in the spectral resolution
      of a recently proposed single-comb terahertz spectroscopy [Opt. Lett.39, 5669
      (2014)]. The improvement is achieved by using a femtosecond optical pulse train
      with a tunable repetition rate. Terahertz comb with tunable spectral line spacing
      generated by the train is detected via nonlinear mixing with a harmonic of a CW
      signal from a microwave frequency synthesizer. By applying this technique to the
      low-pressure gas spectroscopy, we achieved a 100 kHz spectral resolution in
      measuring separate absorption lines of the rotational manifold of fluoroform
      (CF<sub>3</sub>H). 

PMID- 25607193
TI  - Impulse response of nonlinear Schrodinger equation and its implications for pre
      dispersed fiber-optic communication systems.
AB  - In the presence of pre-dispersion, an exact solution of nonlinear Schrodinger
      equation (NLSE) is derived for impulse input. The phase factor of the exact
      solution is obtained in a closed form using the exponential integral. The
      nonlinear interaction among periodically placed impulses launched at the input is
      investigated, and the condition under which these pulses do not exchange energy
      is examined. It is found that if the complex weights of the impulses at the input
      have a secant-hyperbolic envelope and a proper chirp factor, they will propagate
      over long distances without exchanging energy. To describe their interaction, a
      discrete version of NLSE is derived. The derived equation is a form of discrete
      self-trapping (DST) equation, which is found to admit fundamental and higher
      order soliton solutions in the presence of high pre-dispersion. Nonlinear
      eigenmodes derived here may be useful for description of signal propagation and
      nonlinear interaction in highly pre-dispersion fiber-optic systems. 

PMID- 25607194
TI  - Cavity-enhanced frequency doubling from 795nm to 397.5nm ultra-violet coherent
      radiation with PPKTP crystals in the low pump power regime.
AB  - We demonstrate a simple, compact and cost-efficient diode laser pumped frequency
      doubling system at 795 nm in the low power regime. In two configurations, a bow
      tie four-mirror ring enhancement cavity with a PPKTP crystal inside and a semi
      monolithic PPKTP enhancement cavity, we obtain 397.5nm ultra-violet coherent
      radiation of 35mW and 47mW respectively with a mode-matched fundamental power of
      about 110mW, corresponding to a conversion efficiency of 32% and 41%. The low
      loss semi-monolithic cavity leads to the better results. The constructed ultra
      violet coherent radiation has good power stability and beam quality, and the
      system has huge potential in quantum optics and cold atom physics. 

PMID- 25607195
TI  - Optical realization of the radon transform.
AB  - This paper presents a novel optical system for the realization of the Radon
      transform in a single frame. The optical system is simple, fast and accurate and
      consists of a 4F system, where in the 2F plane a vortex like optical element is
      placed. This optical element performs the rotation of the object, which replaces
      the need for mechanically rotating it, as is done in other common optical
      realization techniques of the Radon transform. This optical element is realized
      using a spatial light modulator (SLM) and an amplitude slide. The obtained Radon
      transform is given in Cartesian coordinates, which can subsequently be
      transformed using a computer to a polar set. The proposed concept is supported
      mathematically, numerically and experimentally. 

PMID- 25607196
TI  - Cross-cultural variation of memory colors of familiar objects.
AB  - The effect of cross-regional or cross-cultural differences on color appearance
      ratings and memory colors of familiar objects was investigated in seven different
      countries/regions - Belgium, Hungary, Brazil, Colombia, Taiwan, China and Iran.
      In each region the familiar objects were presented on a calibrated monitor in
      over 100 different colors to a test panel of observers that were asked to rate
      the similarity of the presented object color with respect to what they thought
      the object looks like in reality (memory color). For each object and region the
      mean observer ratings were modeled by a bivariate Gaussian function. A
      statistical analysis showed significant (p < 0.001) differences between the
      region average observers and the global average observer obtained by pooling the
      data from all regions. However, the effect size of geographical region or culture
      was found to be small. In fact, the differences between the region average
      observers and the global average observer were found to of the same magnitude or
      smaller than the typical within region inter-observer variability. Thus, although
      statistical differences in color appearance ratings and memory between regions
      were found, regional impact is not likely to be of practical importance. 

PMID- 25607197
TI  - Optical chirp z-transform processor with a simplified architecture.
AB  - Using a simplified chirp z-transform (CZT) algorithm based on the discrete-time
      convolution method, this paper presents the synthesis of a simplified
      architecture of a reconfigurable optical chirp z-transform (OCZT) processor based
      on the silica-based planar lightwave circuit (PLC) technology. In the simplified
      architecture of the reconfigurable OCZT, the required number of optical
      components is small and there are no waveguide crossings which make fabrication
      easy. The design of a novel type of optical discrete Fourier transform (ODFT)
      processor as a special case of the synthesized OCZT is then presented to
      demonstrate its effectiveness. The designed ODFT can be potentially used as an
      optical demultiplexer at the receiver of an optical fiber orthogonal frequency
      division multiplexing (OFDM) transmission system. 

PMID- 25607198
TI  - Sensitivity and design of grating-assisted bimodal interferometers for integrated
      optical biosensing.
AB  - The sensitivity of bimodal waveguides for integrated optical biosensors is
      compared to single mode waveguides and grating-assisted bimodal interferometers
      are proposed as improved sensor concept. Grating-assisted bimodal interferometers
      are an elegant and compact sensor concept, which features easy fabrication and
      overcomes typical weaknesses of classical Mach-Zehnder interferometers. Long
      period gratings for mode conversion in the proposed sensor concept have been
      simulated employing the FDTD method. Such gratings give full control over the
      power distribution in the waveguides modes, which is not possible with other
      methods. Designs for three typical material systems are given and fabrication
      tolerances were investigated. 

PMID- 25607199
TI  - Intuitive model for the scintillations of a partially coherent beam.
AB  - An intuitive model for the scintillation index of a partially coherent beam is
      developed in which essentially the only critical parameter is the properly
      defined Fresnel number equal to the ratio of the "working" aperture area to the
      area of the Fresnel zone. The model transpired from and is supported by numerical
      simulations using Rytov method for weak fluctuations regime and Tatarskii
      turbulence spectrum with inner scale. The ratio of the scintillation index of a
      partially coherent beam to that of a plane wave displays a characteristic
      minimum, the magnitude of which and its distance from the transmitter are easily
      explained using the intuitive model. A theoretical asymptotic is found for the
      scintillation index of a source with decreasing coherence at this minimum. 

PMID- 25607200
TI  - Direct writing of 150 nm gratings and squares on ZnO crystal in water by using
      800 nm femtosecond laser.
AB  - We present a controllable fabrication of nanogratings and nanosquares on the
      surface of ZnO crystal in water based on femtosecond laser-induced periodic
      surface structures (LIPSS). The formation of nanogrooves depends on both laser
      fluence and writing speed. A single groove with width less than 40 nm and double
      grooves with distance of 150 nm have been produced by manipulating 800 nm
      femtosecond laser fluence. Nanogratings with period of 150 nm, 300 nm and 1000
      nm, and nanosquares with dimensions of 150 * 150 nm<sup>2</sup> were fabricated
      by using this direct femtosecond laser writing technique. 

PMID- 25607201
TI  - Infrared broadband quarter-wave and half-wave plates synthesized from anisotropic
      Bezier metasurfaces.
AB  - In this work a new technique for synthesizing metamaterials using Bezier surfaces
      is introduced. First, the computational efficiency for the optimization of a
      reconfigurable Bezier quarter-wave plate metasurface is compared to the popular
      technique of optimizing pixelized surfaces via a binary Genetic Algorithm (GA).
      For the presented design methodology, a real valued optimization technique is
      employed which is based on the Covariance Matrix Adaptation Evolutionary Strategy
      (CMA-ES). When compared to the GA, the optimizations of Bezier surfaces using CMA
      ES are shown to consistently arrive at better solutions with an order of
      magnitude reduction in the required number of function evaluations. Additionally,
      more examples of Bezier metasurfaces are presented in the form of broadband
      quarter-wave and half-wave plate designs operating at optical wavelengths,
      subsequently exhibiting bandwidths which outperform metasurface designs found in
      the current literature. 

PMID- 25607202
TI  - Comparative study of the accuracy of the PSM and Kogelnik models of diffraction
      in reflection and transmission holographic gratings.
AB  - Calculated diffractive efficiencies in the visible spectral band from lossless
      planar holographic gratings are studied using the PSM and Kogelnik models of
      diffraction for the case of the sigma-polarization. The results are numerically
      compared with rigorous coupled wave calculations over a wide parameter space
      covering both transmission and reflection geometries. For most reflection
      gratings, the PSM model is shown to consistently provide a marginally superior
      estimation of the diffractive efficiency. This is particularly evident in a
      clearly superior description of the diffractive sideband structure for most
      gratings, both in terms of angle and wavelength. For the transmission grating,
      the PSM model continues to provide a relatively good description of diffraction
      at low permittivity modulations and lower incidence angles with respect to the
      grating plane normal. However, overall Kogelnik's theory is shown to provide a
      somewhat superior estimation of diffractive efficiency and a clearly superior
      description of the diffractive side-band structure in the transmission case. 

PMID- 25607204
TI  - Experimental implementation of tightly focused beams with unpolarized transversal
      component at any plane.
AB  - The aim of this paper is to provide a formal framework for designing highly
      focused fields with specific transversal features when the incoming beam is
      partially polarized. More specifically, we develop a field with a transversal
      component that remains unpolarized in the focal area. Special attention is paid
      to the design of the input beam and the development of the experiment. The
      implementation of such fields is possible by using an interferometric setup
      combined with the use of digital holography techniques. Experimental results are
      compared with those obtained numerically. 

PMID- 25607203
TI  - Towards model-based adaptive optics optical coherence tomography.
AB  - The transfer function for optical wavefront aberrations in single-mode fiber
      based optical coherence tomography is determined. The loss in measured OCT signal
      due to optical wavefront aberrations is quantified using Fresnel propagation and
      the calculation of overlap integrals. A distinction is made between a model for a
      mirror and a scattering medium model. The model predictions are validated with
      measurements on a mirror and a scattering medium obtained with an adaptive optics
      optical coherence tomography setup. Furthermore, a one-step defocus correction,
      based on a single A-scan measurement, is derived from the model and verified.
      Finally, the pseudo-convex structure of the optical coherence tomography transfer
      function is validated with the convergence of a hill climbing algorithm. The
      implications of this model for wavefront sensorless aberration correction are
      discussed. 

PMID- 25607205
TI  - Frequency-comb-referenced mid-infrared source for high-precision spectroscopy.
AB  - We report on a tunable continuous-wave mid-infrared optical parametric oscillator
      (OPO), which is locked to a fully stabilized near-infrared optical frequency comb
      using a frequency doubling scheme. The OPO is used for 40 GHz mode-hop-free,
      frequency-comb-locked scans in the wavelength region between 2.7 and 3.4 MUm. We
      demonstrate the applicability of the method to high-precision cavity-ring-down
      spectroscopy of nitrous oxide (N<sub>2</sub>O) and water (H<sub>2</sub>O) at 2.85
      um and of methane (CH<sub>4</sub>) at 3.2 MUm. 

PMID- 25607206
TI  - Novel buried inverse-trapezoidal micropattern for dual-sided light extracting
      backlight unit.
AB  - We devised a novel buried inverse-trapezoidal (BIT) micropattern that can enable
      light extracting to both front and back sides of the backlight unit (BLU). The
      proposed BLU comprised of only a single-sheet light-guide plate (LGP) having the
      BIT micropatterns only on the top surface of the LGP. The proposed BLU shows
      normal directional light emitting characteristics to both the front and back
      sides of the LGP and successfully acts as a planer light source for a dual-sided
      LCD. The proposed BLU has the potential to dramatically reduce the thickness,
      weight and cost of the dual-sided LCD thanks to its single-sheet nature. 

PMID- 25607207
TI  - Mid-infrared plasmon induced transparency in heterogeneous graphene ribbon pairs.
AB  - The control of coherent phenomena in graphene structures is proposed.
      Specifically, plasmon induced transparency (PIT) effect is investigated in a kind
      of simple graphene structures - graphene ribbon pairs. The transparency effect
      are understood by the mode coupling between dipolar and quadrupole plasmons modes
      in graphene ribbons. By using bias voltage tuning or geometry parameters
      changing, the PIT effect can be effectively controlled, which is based on the
      frequency tuning of dipolar or quadrupole modes in ribbons. These properties make
      these structures possess applications in two-dimensional plasmonics devices in
      mid-infrared range. In addition, the tuning of PIT in graphene ribbon pairs opens
      an avenue for active coherent control in plasmonics. 

PMID- 25607208
TI  - Modulation formats for multi-core fiber transmission.
AB  - We investigate high dimensional modulation formats for multi-core fibers (MCFs)
      and spatial superchannels. We show that the low skew variations between MCF cores
      maybe exploited to generate 'multi-core' formats that offer significant
      advantages over independently transmitting conventional 4-dimensional formats in
      each core. We describe how pulse position modulation formats may be transposed to
      the spatial domain and then investigate a family of modulation formats referred
      to as core-coding, one of which has the same power and spectral efficiency as
      polarization switched quaternary phase shift keying but with half of the optical
      power, potentially improving non-linear tolerance for long distance transmission,
      albeit at the cost of implementation challenges. Finally, we investigate the
      application of set-partitioning to multi-core formats using a single-parity check
      bit transmitted in one quadrature of one polarization in one of the cores and
      polarization-division multiplexing quadrature phase shift keying data in all
      remaining cores. We observe that for high core counts, an advantage of almost 3
      dB in asymptotic power efficiency may be obtained with negligible impact on
      spectral efficiency, which translates into experimentally measured reduction in
      the required optical signal-to-noise ratio of up to 1.8 dB at a bit-error-rate of
      10<sup>-5</sup> and the same data-rate, and additional transmission reach of up
      to 20%. 

PMID- 25607209
TI  - Manipulation of heat-diffusion channel in laser thermal lithography.
AB  - Laser thermal lithography is a good alternative method for forming small pattern
      feature size by taking advantage of the structural-change threshold effect of
      thermal lithography materials. In this work, the heat-diffusion channels of laser
      thermal lithography are first analyzed, and then we propose to manipulate the
      heat-diffusion channels by inserting thermal conduction layers in between
      channels. Heat-flow direction can be changed from the in-plane to the out-of
      plane of the thermal lithography layer, which causes the size of the structural
      change threshold region to become much smaller than the focused laser spot
      itself; thus, nanoscale marks can be obtained. Samples designated as "glass
      substrate/thermal conduction layer/thermal lithography layer (100 nm)/thermal
      conduction layer" are designed and prepared. Chalcogenide phase-change materials
      are used as thermal lithography layer, and Si is used as thermal conduction layer
      to manipulate heat-diffusion channels. Laser thermal lithography experiments are
      conducted on a home-made high-speed rotation direct laser writing setup with 488
      nm laser wavelength and 0.90 numerical aperture of converging lens. The writing
      marks with 50-60 nm size are successfully obtained. The mark size is only about
      1/13 of the focused laser spot, which is far smaller than that of the light
      diffraction limit spot of the direct laser writing setup. This work is useful for
      nanoscale fabrication and lithography by exploiting the far-field focusing light
      system. 

PMID- 25607210
TI  - Theoretical and experimental studies of polarization fluctuations over
      atmospheric turbulent channels for wireless optical communication systems.
AB  - In wireless optical communications (WOC), polarization multiplexing systems and
      coherent polarization systems have excellent performance and wide applications,
      while its state of polarization affected by atmospheric turbulence is not clearly
      understood. This paper focuses on the polarization fluctuations caused by
      atmospheric turbulence in a WOC link. Firstly, the relationship between the
      polarization fluctuations and the index of refraction structure parameter is
      introduced and the distribution of received polarization angle is obtained
      through theoretical derivations. Then, turbulent conditions are adjusted and
      measured elaborately in a wide range of scintillation indexes (SI). As a result,
      the root-mean-square (RMS) variation and probability distribution function (PDF)
      of polarization angle conforms closely to that of theoretical model. 

PMID- 25607211
TI  - Formal selection rules for Brillouin scattering in integrated waveguides and
      structured fibers.
AB  - We derive formal selection rules for Stimulated Brillouin Scattering (SBS) in
      structured waveguides. Using a group-theoretical approach, we show how the
      waveguide symmetry determines which optical and acoustic modes interact for both
      forward and backward SBS. We present a general framework for determining this
      interaction and give important examples for SBS in waveguides with rectangular,
      triangular and hexagonal symmetry. The important role played by degeneracy of the
      optical modes is illustrated. These selection rules are important for SBS-based
      device design and for a full understanding the physics of SBS in structured
      waveguides. 

PMID- 25607212
TI  - Optical fiber with nanostructured cladding of TiO2 nanoparticles self-assembled
      onto a side polished fiber and its temperature sensing.
AB  - We demonstrated temperature sensing of a fiber with nanostructured cladding,
      which was constructed by titanium dioxide TiO2 nanoparticles self-assembled onto
      a side polished optical fiber (SPF). Significantly enhanced interaction between
      the propagating light and the TiO2 nanoparticles (TN) can be obtained via strong
      evanescent field of the SPF. The strong light-TN interaction results in
      temperature sensing with a maximum optical power variation of ~4dB in SPF
      experimentally for an external environment temperature varying from -7.8 degrees
      C to 77.6 degrees C. The novel temperature sensing device shows a linear
      correlation coefficient of better than 99.4%, and a sensitivity of ~0.044 dB/
      degrees C. The TN-based all-fiber-optic temperature sensing characteristics was
      successfully demonstrated, and it is compatible with fiber-optic interconnections
      and high potential in photonics applications.

PMID- 25607213
TI  - Detecting atoms trapped in an optical lattice using a tapered optical nanofiber.
AB  - Optical detection of structures with dimensions smaller than an optical
      wavelength requires devices that work on scales beyond the diffraction limit.
      Here we present the possibility of using a tapered optical nanofiber as a
      detector to resolve individual atoms trapped in an optical lattice in the Mott
      insulator phase. We show that the small size of the fiber combined with an
      enhanced photon collection rate can allow for the attainment of large and
      reliable measurement signals. 

PMID- 25607214
TI  - Pump-probe quantum state tomography in a semiconductor optical amplifier.
AB  - Pump-probe quantum state tomography was applied to the transmission of a coherent
      state through an In(Ga)As based quantum dot optical amplifier during the
      interaction with an optical pump pulse. The Wigner function and the statistical
      moments of the field were extracted and used to determine the degree of
      population inversion and the signal-to-noise ratio in a sub-picosecond time
      window. 

PMID- 25607215
TI  - Focus issue introduction: space-division multiplexing.
AB  - Since the publication of the first focus issue [Opt. Express 19(11), 2011],
      single-fiber transmission capacity has eclipsed the 1 Pb/s mark. All aspects
      related to space-division multiplexing including fiber, passive components
      [(de)multiplexer, couplers], active components (EDFA and Raman amplifiers),
      switching and routing elements (ROADM and WSS), as well as transmission and
      networking have progressed rapidly. This focus issue is intended to bring
      together the most up-to-date research in space-division multiplexing, including
      fibers, passive and active components, transmission systems and networking. 

PMID- 25607216
TI  - PKA/CREB regulates the constitutive promoter activity of the USP22 gene.
AB  - The human ubiquitin-specific processing enzyme 22 (USP22) plays a crucial role in
      regulating cell cycle processes and its overexpression has been linked to tumor
      progression. However, the mechanisms leading to USP22 transcriptional activation
      in human cancer cells are still unclear. Previously, we characterized the 5'
      flanking sequence of the human USP22 gene and found a potential CREB/ATF binding
      site within the basic promoter region. The present study found that this site was
      required for constitutive USP22 transcriptional activity in HeLa and HepG2 cells.
      Chromatin immunoprecipitation assay confirmed that CREB interacted with this
      site. siRNA knockdown of CREB decreased USP22 transcriptional activation and
      endogenous expression, whereas CREB overexpression did not affect transcriptional
      levels. Furthermore, USP22 promoter activity and expression were decreased by
      inhibiting PKA with H-89, but were not responsive to forskolin induction. All of
      these results demonstrate that PKA/CREB is involved in the regulation of
      constitutive promoter activity of the USP22 gene.

PMID- 25607217
TI  - Role of adenovirus-mediated retinoblastoma 94 in the treatment of human non-small
      cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related
      mortality despite the fact that great advances have been made in therapeutic
      treatment methods. Therefore, in the present study, the role of adenovirus
      mediated retinoblastoma 94 (Ad-RB94) gene therapy in NSCLC was investigated.
      Following treatment with Ad-RB94, the proportion of A549 cells in the G2/M phase
      was increased. In the mouse xenograft model, the overexpression of RB94 inhibited
      the tumor growth compared with the control group and the Ad--LacZ-treated group.
      In the transplanted tumors, the overexpression of RB94 induced the apoptosis of
      tumors as well as an increase in the mRNA levels of cyclinB1. In conclusion, the
      results of the present study suggested that RB94 may effectively inhibit NSCLC
      tumor cell growth by inducing G2/M cell cycle arrest and apoptosis, indicating
      that RB94 may be a promising candidate for adjuvant therapy with radiation or
      chemotherapy in NSCLC.

PMID- 25607218
TI  - State-Resolved Quantum Dynamics of Photodetachment of HCO2(-)/DCO2(-) on an
      Accurate Global Potential Energy Surface.
AB  - Full-dimensional quantum dynamics studies of the photodetachment of HCO2(-) and
      DCO2(-) are reported using a wave-packet method on an accurate global potential
      energy surface of the neutral HOCO/HCO2 system. The calculated photoelectron
      spectra reproduced both the positions and widths of the main HCO2 and DCO2 peaks
      observed in experiment. Specifically, both the (2)A1 and (2)B2 resonance peaks of
      the neutral radicals were identified in our simulations thanks to the adiabatic
      PES that captures both the (2)A1 and (2)B2 minima. The narrow widths and isotope
      effect of the lowest resonances are indicative of tunneling-facilitated
      predissociation. Furthermore, the dissociation product CO2 was found to be
      excited in both its symmetric stretching and bending modes, which are coupled via
      a strong Fermi resonance, but rotationally cold, in good agreement with the
      recent photoelectron-photodetachment coincidence experiments. 

PMID- 25607219
TI  - Encapsulation and covalent binding of molecular payload in enzymatically
      activated micellar nanocarriers.
AB  - The high selectivity and often-observed overexpression of specific disease
      associated enzymes make them extremely attractive for triggering the release of
      hydrophobic drug or probe molecules from stimuli-responsive micellar
      nanocarriers. Here we utilized highly modular amphiphilic polymeric hybrids,
      composed of a linear hydrophilic polyethylene glycol (PEG) and an esterase
      responsive hydrophobic dendron, to prepare and study two diverse strategies for
      loading of enzyme-responsive micelles. In the first type of micelles, hydrophobic
      coumarin-derived dyes were encapsulated noncovalently inside the hydrophobic core
      of the micelle, which was composed of lipophilic enzyme-responsive dendrons. In
      the second type of micellar nanocarrier the hydrophobic molecular cargo was
      covalently linked to the end-groups of the dendron through enzyme-cleavable
      bonds. These amphiphilic hybrids self-assembled into micellar nanocarriers with
      their cargo covalently encapsulated within the hydrophobic core. Both types of
      micelles were highly responsive toward the activating enzyme and released their
      molecular cargo upon enzymatic stimulus. Importantly, while faster release was
      observed with noncovalent encapsulation, higher loading capacity and slower
      release rate were achieved with covalent encapsulation. Our results clearly
      indicate the great potential of enzyme-responsive micellar delivery platforms due
      to the ability to tune their payload capacities and release rates by adjusting
      the loading strategy. 

PMID- 25607220
TI  - Thinking differently: working together for better care.
AB  - This paper describes the development and outcomes from 'joint working' between
      Prince of Wales Hospital and BD (Becton, Dickinson and Company) in Australia.
      'Joint working' is a term used within the English National Health Service to
      describe health system and industry partners working together to create novel
      service models which benefit patients. The joint working process broadened the
      perspective of both parties through learning from each other and so enhanced the
      range of tools they each bring to their work.

PMID- 25607221
TI  - Fast surface crystallization of molecular glasses: creation of depletion zones by
      surface diffusion and crystallization flux.
AB  - Molecular glasses can grow crystals much faster at the free surface than in the
      interior. A property of this process is the creation of depressed grooves or
      depletion zones around the crystals on the initially flat amorphous surface. With
      scanning electron microscopy and atomic force microscopy, we studied this
      phenomenon in indomethacin, which crystallizes in two polymorphs (alpha and
      gamma) of different morphologies. The observed depletion zones are well
      reproduced by the known coefficients of surface diffusion and the velocities of
      crystal growth. At the slow-growing flanks of needle-like alpha IMC crystals,
      depletion zones widen and deepen over time according to the expected kinetics for
      surface diffusion responding to a crystallization flux. Before fast-advancing
      growth fronts, depletion zones have less time to develop; their steady-state
      dimensions agree with the same model revised for a moving phase boundary. These
      results support the view that surface diffusion enables fast surface crystal
      growth on molecular glasses. Our finding helps understand crystal growth in thin
      films in which the formation of deep depletion zones can cause dewetting and
      alter growth kinetics. 

PMID- 25607222
TI  - Severe Intraventricular Hemorrhage in Extremely Premature Infants: Are high
      Carbon Dioxide Pressure or Fluctuations the Culprit?
AB  - OBJECTIVE: This study aims to examine the association between measures of
      hypercapnia and fluctuation in Pco 2 and severe intraventricular hemorrhage (IVH)
      and to evaluate the prevalence of hypercapnia, hypocapnia, and fluctuations in
      Pco 2 in the initial 72 hours of life among premature infants. STUDY DESIGN:
      Retrospective study of premature infants with birth weight < 1,250 g, who were
      receiving some respiratory support. All blood gases obtained in the first 3 days
      of life were collected. Univariate and multivariate analyses were performed to
      assess the association of hypercapnia, and fluctuations in Pco 2 with severe IVH.
      RESULT: Our cohort included 285 patients, of whom 84% were intubated. Only 20%
      patients had all blood gases in the normocapnia range; 9% had at least 1 gas with
      hypercapnia; 51% had at least 1 gas with hypocapnia, and 20% patients had both
      hypercapnia and hypocapnia at different times. Infants with severe IVH (n = 41)
      had significantly higher peak Pco 2 and greater fluctuations in Pco 2 within a
      short interval, compared with those without severe IVH (n = 227). After
      controlling for gestational age, gender, antenatal steroid exposure, presence of
      hypercapnia, and Apgar score at 5 minutes, fluctuation in Pco 2 remained
      significantly associated with severe IVH. CONCLUSION: Fluctuations in Pco 2
      within a short period may be more significantly associated with severe IVH than
      the mere presence of hypercapnia.

PMID- 25607223
TI  - Cardiac Troponin Levels in Neonates Who Require ECMO for Noncardiac Indications
      Are Elevated in Nonsurvivors.
AB  - OBJECTIVE: The aim of the study is to determine the utility of cardiac troponin
      (cTnI) as a marker of mortality and morbidity in newborn infants who require
      extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Retrospective medical
      chart analysis of term or near-term newborn infants treated with ECMO from 2002
      to 2012 at a single Level III neonatal intensive care unit. Data analyzed
      included serial serum cTnI measurements, clinical and demographic
      characteristics, pre-ECMO laboratory values, and ECMO laboratory values and
      outcomes. RESULTS: Survival (27/46) was significantly related to birth weight
      (3,413.9 +/- 662.3 vs. 2,667.7 +/- 478.3 g, p < 0.001), outborn status (22/30 vs.
      5/13, p = 0.0021), and the absence of a congenital diaphragmatic hernia (22/30
      vs. 5/18, p = 0.0021). Mean peak cTnI did not differ between survivors and
      nonsurvivors but when peak cTnI was < 2.8 ng/mL, survival was 64% compared with
      22% when it was > 2.8 ng/mL (p = 0.0224; odds ratio = 0.160, 95% confidence
      interval = 0.0292-0.8778). By multivariate analysis, peak cTnI > 2.1 was a
      significant risk factor for nonsurvival, p = 0.0497. The area under the curve of
      a receiver-operator analysis using peak cTnI > 2.1, birth weight, and birthplace
      was 0.89, p < 0.001. CONCLUSION: cTnI is an independent biomarker for poor
      outcome in neonates who receive ECMO therapy for noncardiac generations.

PMID- 25607224
TI  - Cesarean Delivery and Risk for Subsequent Ectopic Pregnancy.
AB  - OBJECTIVE: This study aims to examine the risk for subsequent ectopic pregnancy
      in women with prior cesarean delivery. STUDY DESIGN: Women with a history of at
      least one cesarean delivery in the state of Utah during 1996 to 2011 were
      identified and compared with women with vaginal delivery only. The primary
      outcome was subsequent ectopic pregnancy. Data were analyzed by multivariate
      logistic regression and stratified by first, second, or third live births. Model
      covariates included maternal age, ethnicity, marital status, education level,
      gravidity, and prior ectopic pregnancy. RESULTS: Overall, 260,249 women with at
      least one live birth were identified. After exclusions, 255,082, 154,930, and
      70,228 women had at least one, two, and three prior live births that lead to 531,
      199, and 62 subsequent ectopic pregnancies, respectively. Women who had one prior
      cesarean delivery were not at increased risk for subsequent ectopic pregnancy in
      relation to women with no prior cesarean delivery. However, women with two of
      two, two of three, or three of three prior cesareans had increased risk for
      subsequent ectopic pregnancy with odds ratios (95% confidence interval) of 1.54
      (1.06-2.22), 3.50 (1.49-8.24), and 1.99 (1.00-3.98), respectively. CONCLUSION:
      History of two or three cesarean deliveries is associated with increased risk for
      subsequent ectopic pregnancy.

PMID- 25607225
TI  - Effect of Growth Restriction on Fetal Heart Rate Patterns in the Second Stage of
      Labor.
AB  - OBJECTIVE: We aimed to estimate the effect of intrauterine growth restriction
      (IUGR) on electronic fetal monitoring (EFM) patterns in the second stage of
      labor. STUDY DESIGN: We performed a 5-year retrospective cohort study of
      consecutive singleton, non-anomalous, term gestations. We compared IUGR infants,
      those with a birth weight less than the 10th percentile, with non-IUGR infants,
      those greater than or equal to the 10th percentile. Our primary outcome was the
      EFM patterns in the 30 minutes before delivery. A secondary analysis was
      performed excluding infants with composite morbidity. Logistic regression was
      used to adjust for body mass index, race, nulliparity, induction, and protracted
      labor. RESULTS: Out of the 5,388 infants, 652 (12.1%) were IUGR. IUGR fetuses had
      less accelerations (29.0 vs. 35.9%, p < 0.01), even among apparently normal
      infants (29.0 vs. 36.4%, p < 0.01). IUGR fetuses had a higher risk of
      decelerations, and in all, IUGR accounted for 6% of late decelerations
      (attributable risk 0.06, 95% confidence interval 0.02-0.10). There was no
      significant association between IUGR and bradycardia or minimal variability.
      CONCLUSION: Growth restriction at term confers an increased risk of late
      decelerations, even in the absence of neonatal morbidity. EFM patterns may
      require different interpretations based on a priori risk and clinical factors.

PMID- 25607227
TI  - Premedication Use Before Nonemergent Intubation in the Newborn Infant.
AB  - OBJECTIVE: In 2010, an American Academy of Pediatrics (AAP) clinical report
      recommended that except for emergent situations, premedication should be used for
      all endotracheal intubations in newborns. The purpose of this study is to
      ascertain the current practice of premedication before elective intubation. STUDY
      DESIGN: An online, survey-based questionnaire on the practice of premedication
      before nonemergent intubations was distributed via e-mail to neonatologists who
      are members of the Perinatal Section of the AAP. RESULTS: Although 72% of
      respondents believed premedication should be used in nonemergent intubations,
      only 34% of the respondents report frequently premedicating before intubation
      with significant variation among the neonatal units (46% among level 4 units and
      27% in level 3 and 2 units) p = 0.000. About 44% of respondents report having a
      written protocol or guideline on premedication which significantly correlated
      with the use of premedication (62% in level 4, 33% in level 3, and 16% in level 2
      units), p = 0.000. CONCLUSION: Despite a recent AAP clinical report recommending
      the use of premedication before nonemergent endotracheal intubation, only one
      third of neonatologists report frequent use of premedication and less than half
      of the institutions have a written protocol on premedication.

PMID- 25607226
TI  - A Pilot Randomized Controlled Trial of Early versus Routine Caffeine in Extremely
      Premature Infants.
AB  - OBJECTIVE: This study aims to compare the effects of early and late (routine)
      initiation of caffeine in nonintubated preterm neonates. STUDY DESIGN: A total of
      21 neonates < 29 weeks gestational age were randomized to receive intravenous
      caffeine citrate (20 mg/kg) or placebo either before 2 hours of age (early) or at
      12 hours of age (routine). This was an observational trial to determine the power
      needed to reduce the need for endotracheal intubation by 12 hours of age. Other
      outcomes included comparisons of cerebral oxygenation, systemic and pulmonary
      blood flow, hemodynamics, hypotension treatment, oxygen requirement, and head
      ultrasound findings. RESULTS: There was no difference in the need for intubation
      (p = 0.08), or vasopressors (p = 0.21) by 12 hours of age. Early caffeine was
      associated with improved blood pressure (p = 0.03) and systemic blood flow
      (superior vena cava flow, p = 0.04 and right ventricular output, p = 0.03). Heart
      rate, left ventricular output, and stroke volume were not significantly affected.
      Cerebral oxygenation transiently decreased 1 hour after caffeine administration.
      There were no differences in other outcomes. CONCLUSION: This pilot study
      demonstrated the feasibility of conducting such a trial in extremely preterm
      neonates. We found that early caffeine administration was associated with
      improved hemodynamics. Larger studies are needed to determine whether early
      caffeine reduces intubation, intraventricular hemorrhage, and related long-term
      outcomes.

PMID- 25607228
TI  - Tidal volume in infants with congenital diaphragmatic hernia supported with
      conventional mechanical ventilation.
AB  - OBJECTIVE: This study aims to test the hypothesis that the tidal volume (VT)
      required for maintaining eucapnia in infants with congenital diaphragmatic hernia
      (CDH) is not reduced to the same degree as their lung mass. STUDY DESIGN: Records
      of infants with CDH admitted to our hospital from 1997 to 2009 managed with
      conventional ventilation were reviewed. Demographics, ventilator settings,
      observed VT, respiratory rate (RR), and blood gas values pre- and postsurgery
      were recorded. Minute ventilation (MV) was calculated as a product of RR * VT.
      Only VT values with corresponding Paco 2 between 35 and 60 mm Hg were included.
      Mean VT/kg and MV/kg were calculated for each patient. Forty term/late preterm
      infants ventilated for lung disease other than CDH or pulmonary hypoplasia served
      as controls. RESULTS: Birth weights of the 19 patients with CDH and 40 control
      infants were similar (3,360 +/- 480 g and 3,300 +/- 640 g). Mean gestational age
      was 38.5 +/- 2 and 37.4 +/- 1.5 week, p = 0.02. Infants with CDH required similar
      VT and MV as controls to maintain equal Paco 2. CONCLUSIONS: Infants with CDH
      require similar VT to clear their CO2 production compared with infants of similar
      size without pulmonary hypoplasia. These are the first reference values to guide
      selection of VT in infants with CDH.

PMID- 25607229
TI  - The Clinical Characters of Congenital Choledochal Cysts in Perinatal Patients: A
      Retrospective Analysis in a Single Institution.
AB  - OBJECT: We aimed to investigate the clinical characters of congenital choledochal
      cysts (CC) in perinatal patients and to determine the most suitable time for
      their management. STUDY DESIGN: We retrospectively analyzed all the data of
      patients with CC in our hospital between 2003 and 2013. Clinical characteristics
      during the perinatal, infancy, and childhood periods were examined. RESULTS: A
      total of 216 cases were analyzed, including 12, 39, and 165 patients in their
      perinatal, infancy, and childhood periods, respectively. The incidence of
      abdominal pain and jaundice in the perinatal group was lower than that in other
      groups (p < 0.0001; p = 0.001). The incidence of abnormal inflammatory markers
      and liver function in perinatal cases was lower than in the other cases (p =
      0.012; p = 0.002). The receiver-operating characteristic curves for liver
      function indicated that the cut-off point for age at which liver damage was found
      was 120 days. Of the 12 perinatal cases, there were no significant differences,
      with regards to operative time and hospital stay, between open and laparoscopic
      surgical approaches (p = 0.164; p = 0.722). CONCLUSION: Abdominal pain, jaundice,
      inflammatory markers, and liver function in perinatal patients with CC are better
      than in the infancy and childhood groups. We recommend surgical treatment before
      120 days of age.

PMID- 25607230
TI  - Association of influenza vaccination on decreased stillbirth rate.
AB  - OBJECTIVE: We have previously shown a decrease in the overall stillbirth rate at
      our institution in women receiving the seasonal influenza vaccine during
      pregnancy. The goal of this study was to ascertain factors associated with this
      decrease. STUDY DESIGN: This was a retrospective cohort study examining the
      stillbirth rate, etiology, autopsy findings, and placental pathology in pregnant
      women receiving the seasonal trivalent inactive influenza vaccine during five
      influenza seasons between 2003 and 2008. All stillbirths at our institution are
      investigated by a committee and an etiology is assigned. Autopsy is offered to
      all patients and placental evaluation is performed routinely. RESULTS: During the
      study period, 8,690 pregnant women received the seasonal influenza vaccine
      antepartum and delivered at our institution. Thirty of these births were
      complicated by stillbirth as compared with 436 stillbirths in the 76,153 women
      not vaccinated (0.35 vs. 0.57%, p = 0.006). No association was identified between
      assigned causes of stillbirth when comparing vaccinated and nonvaccinated women.
      CONCLUSION: No specific etiology commonly associated with stillbirth was
      identified to have been affected by maternal antepartum influenza vaccination.

PMID- 25607231
TI  - Distance dependence of the energy transfer rate from a single semiconductor
      nanostructure to graphene.
AB  - The near-field Coulomb interaction between a nanoemitter and a graphene monolayer
      results in strong Forster-type resonant energy transfer and subsequent
      fluorescence quenching. Here, we investigate the distance dependence of the
      energy transfer rate from individual, (i) zero-dimensional CdSe/CdS nanocrystals
      and (ii) two-dimensional CdSe/CdS/ZnS nanoplatelets to a graphene monolayer. For
      increasing distances d, the energy transfer rate from individual nanocrystals to
      graphene decays as 1/d(4). In contrast, the distance dependence of the energy
      transfer rate from a two-dimensional nanoplatelet to graphene deviates from a
      simple power law but is well described by a theoretical model, which considers a
      thermal distribution of free excitons in a two-dimensional quantum well. Our
      results show that accurate distance measurements can be performed at the single
      particle level using graphene-based molecular rulers and that energy transfer
      allows probing dimensionality effects at the nanoscale. 

PMID- 25607232
TI  - The centrosomal component CEP161 of Dictyostelium discoideum interacts with the
      Hippo signaling pathway.
AB  - CEP161 is a novel component of the Dictyostelium discoideum centrosome which was
      identified as binding partner of the pericentriolar component CP250. Here we show
      that the amino acids 1-763 of the 1381 amino acids CEP161 are sufficient for
      CP250 binding, centrosomal targeting and centrosome association. Analysis of AX2
      cells over-expressing truncated and full length CEP161 proteins revealed defects
      in growth and development. By immunoprecipitation experiments we identified the
      Hippo related kinase SvkA (Hrk-svk) as binding partner for CEP161. Both proteins
      colocalize at the centrosome. In in vitro kinase assays the N-terminal domain of
      CEP161 (residues 1-763) inhibited the kinase activity of Hrk-svk. A comparison of
      D. discoideum Hippo kinase mutants with mutants overexpressing CEP161
      polypeptides revealed similar defects. We propose that the centrosomal component
      CEP161 is a novel player in the Hippo signaling pathway and affects various
      cellular properties through this interaction. 

PMID- 25607233
TI  - Influence of different sports on bone mass in growing girls.
AB  - The aim of this study was to analyse whether there are differences in bone mass
      in girls playing different sports. Two hundred girls (10.6 +/- 1.5 years old,
      Tanner stages I-III) participated in the study and were divided into groups of 40
      (swimmers, soccer players, basketball players, handball players and controls).
      Bone mineral content and bone mineral density (BMD) (whole body and hip) were
      measured using dual-energy X-ray absorptiometry. The degree of sexual development
      was determined using Tanner test, and physical activity habits were recorded
      through a questionnaire designed ad hoc for this research. Girls were divided by
      pubertal stage and the type of sport. In the prepubertal group, intertrochanteric
      BMD was significantly higher in both handball and soccer players compared with
      the control group (P < 0.05). Furthermore, in the pubertal group, total BMD, mean
      arms BMD, pelvis BMD, femoral neck BMD, intertrochanteric BMD and Ward's triangle
      BMD were significantly higher in soccer and handball players compared with the
      control group (P < 0.05), and the swimmers showed significantly higher values in
      the mean arms BMD compared with the control group (P < 0.01). Our data suggest
      that sport practice during puberty, especially in activities that support the
      body weight, may be an important factor in achieving a high peak bone mass and
      improving bone health in girls. 

PMID- 25607234
TI  - MicroRNA-206 attenuates tumor proliferation and migration involving the
      downregulation of NOTCH3 in colorectal cancer.
AB  - Colorectal cancer (CRC) is the most common cancer diagnosed worldwide, and the
      development of metastases is a major cause of mortality. Accumulating evidence
      suggests that microRNAs are important in carcinogenesis by affecting the
      expression of genes that regulate cancer progression. A number of studies have
      shown that miR-206 is frequently downregulated in many human malignancies,
      including CRC, and is associated with a more malignant phenotype. Previous
      studies involving HeLa and C2C12 cells have validated the inhibitory mechanism of
      miR-206 via NOTCH3 targeting. However, whether or not the interplay between miR
      206 and NOTCH3 also occurs in CRC is unknown. Therefore, we investigated the
      tumor suppressive and metastatic effects of miR-206 and its target, NOTCH3, in
      CRC. Based on the inverse association between the expression of miR-206 and
      NOTCH3 in CRC tissues, miR-206 mimics were transiently transfected into the SW480
      (and its metastatic strain) and SW620 colon cancer cell lines. Upregulation of
      miR-206 inhibited cancer cell prolife-ration and migration, blocked the cell
      cycle, and activated apoptosis. The tumor suppressive capacity of miR-206 had a
      similar effect on CRC cells, although with a different metastatic potential, and
      may be explained by direct NOTCH3 signaling inhibition and indirect cross-talk
      with other signaling pathways involving CDH2 and MMP-9. These results support miR
      206 as a tumor suppressor in CRC and suggest a potential therapeutic target for
      clinical intervention.

PMID- 25607235
TI  - Selenium preferentially accumulates in the eye lens following embryonic exposure:
      a confocal X-ray fluorescence imaging study.
AB  - Maternal transfer of elevated selenium (Se) to offspring is an important route of
      Se exposure for fish in the natural environment. However, there is a lack of
      information on the tissue specific spatial distribution and speciation of Se in
      the early developmental stages of fish, which provide important information about
      Se toxicokinetics. The effect of maternal transfer of Se was studied by feeding
      adult zebrafish a Se-elevated or a control diet followed by collection of larvae
      from both groups. Novel confocal synchrotron-based techniques were used to
      investigate Se within intact preserved larvae. Confocal X-ray fluorescence
      imaging was used to compare Se distributions within specific planes of an intact
      larva from each of the two groups. The elevated Se treatment showed substantially
      higher Se levels than the control; Se preferentially accumulated to highest
      levels in the eye lens, with lower levels in the retina, yolk and other tissues.
      Confocal X-ray absorption spectroscopy was used to determine that the speciation
      of Se within the eye lens of the intact larva was a selenomethionine-like
      species. Preferential accumulation of Se in the eye lens may suggest a direct
      cause-and-effect relationship between exposure to elevated Se and Se-induced
      ocular impairments reported previously. This study illustrates the effectiveness
      of confocal X-ray fluorescence methods for investigating trace element
      distribution and speciation in intact biological specimens. 

PMID- 25607236
TI  - Berberine as a therapy for type 2 diabetes and its complications: From mechanism
      of action to clinical studies.
AB  - The incidence of type 2 diabetes is increasing rapidly worldwide, and the
      development of novel anti-diabetic drugs is emerging. However, most anti-diabetic
      drugs cannot be used in patients with hepatic dysfunction, renal disease, and
      heart disease, which makes pharmacological therapy of type 2 diabetes
      complicated. Despite continued introduction of novel agents, the search for an
      ideal drug that is useful as both a hypoglycemic agent and to reduce diabetes
      related complications remains elusive. Berberine is an isoquinoline alkaloid
      extract that has shown promise as a hypoglycemic agent in the management of
      diabetes in animal and human studies. Mechanistic studies have revealed
      beneficial effects of berberine on diabetes-related complications. Although there
      have been few clinical reports of the anti-diabetic effects of berberine, little
      documentation of adverse effects in humans positions it as a potential candidate
      drug to treat type 2 diabetes. In the present review, the anti-diabetic mechanism
      of berberine, its effect on diabetes-related complications, and its recent use in
      human clinical studies is highlighted. In addition, we summarize the different
      treatments for type 2 diabetes in adults and children.

PMID- 25607237
TI  - Genetically enhanced lysozyme evades a pathogen derived inhibitory protein.
AB  - The accelerating spread of drug-resistant bacteria is creating demand for novel
      antibiotics. Bactericidal enzymes, such as human lysozyme (hLYZ), are interesting
      drug candidates due to their inherent catalytic nature and lack of susceptibility
      to the resistance mechanisms typically directed toward chemotherapeutics.
      However, natural antibacterial enzymes have their own limitations. For example,
      hLYZ is susceptible to pathogen derived inhibitory proteins, such as Escherichia
      coli Ivy. Here, we describe proof of concept studies demonstrating that hLYZ can
      be effectively redesigned to evade this potent lysozyme inhibitor. Large
      combinatorial libraries of hLYZ were analyzed using an innovative screening
      platform based on microbial coculture in hydrogel microdroplets. Isolated hLYZ
      variants were orders of magnitude less susceptible to E. coli Ivy yet retained
      high catalytic proficiency and inherent antibacterial activity. Interestingly,
      the engineered escape variants showed a disadvantageous increase in
      susceptibility to the related Ivy ortholog from Pseudomonas aeruginosa as well as
      an unrelated E. coli inhibitory protein, MliC. Thus, while we have achieved our
      original objective with respect to escaping E. coli Ivy, engineering hLYZ for
      broad-spectrum evasion of proteinaceous inhibitors will require consideration of
      the complex and varied determinants that underlie molecular recognition by these
      emerging virulence factors. 

PMID- 25607239
TI  - H3K9 histone methyltransferase G9a ameliorates dilated cardiomyopathy via the
      downregulation of cell adhesion molecules.
AB  - Dilated cardiomyopathy (DCM) is one of the leading causes of mortality; however,
      the underlying molecular mechanisms of DCM remain to be elucidated. H3K9 histone
      methyltransferase G9a has been previously characterized, although its functions
      in DCM are not yet understood. Cell adhesion molecules (CAM) are highly expressed
      in diseased human hearts and were thought to contribute to chronic degeneration
      in cardiac incompetence; however, it has been suggested that G9a may suppress the
      effects of CAM. The aim of the present study was to investigate whether G9a
      decreased the risk of DCM via regulation of CAM expression. A rat model of DCM
      was induced using furazolidone (FZ) treatment and numerous parameters were
      examined. G9a RNA interference (RNAi) was applied to primary neonatal
      cardiomyocytes (PNCs). Reverse transcription quantitative polymerase chain
      reaction and western blot analyses were used to examine the expression levels of
      G9a in the DCM model and PNCs. The growth rate of PNCs was evaluated following
      G9a RNAi and FZ treatment. The results confirmed that the expression levels of
      G9a were significantly decreased in the DCM model compared with those in the
      control group (P<0.01). Conversely, CAM expression levels were significantly
      increased in the DCM model compared with those in the control group (P<0.01). In
      PNCs, the expression of CAM was upregulated following G9a silencing using RNAi.
      Following three-day culture, the growth rate of PNCs was inhibited by 70 and 35%
      following FZ treatment and G9a RNAi, respectively. In conclusion, G9a ameliorated
      DCM via downregulation of CAMs, therefore indicating its potential for use in the
      treatment of DCM.

PMID- 25607238
TI  - Hypoxic epithelial necrosis triggers neutrophilic inflammation via IL-1 receptor
      signaling in cystic fibrosis lung disease.
AB  - RATIONALE: In many organs, hypoxic cell death triggers sterile neutrophilic
      inflammation via IL-1R signaling. Although hypoxia is common in airways from
      patients with cystic fibrosis (CF), its role in neutrophilic inflammation remains
      unknown. We recently demonstrated that hypoxic epithelial necrosis caused by
      airway mucus obstruction precedes neutrophilic inflammation in Scnn1b-transgenic
      (Scnn1b-Tg) mice with CF-like lung disease. OBJECTIVES: To determine the role of
      epithelial necrosis and IL-1R signaling in the development of neutrophilic airway
      inflammation, mucus obstruction, and structural lung damage in CF lung disease.
      METHODS: We used genetic deletion and pharmacologic inhibition of IL-1R in Scnn1b
      Tg mice and determined effects on airway epithelial necrosis; levels of IL
      1alpha, keratinocyte chemoattractant, and neutrophils in bronchoalveolar lavage;
      and mortality, mucus obstruction, and structural lung damage. Furthermore, we
      analyzed lung tissues from 21 patients with CF and chronic obstructive pulmonary
      disease and 19 control subjects for the presence of epithelial necrosis.
      MEASUREMENTS AND MAIN RESULTS: Lack of IL-1R had no effect on epithelial necrosis
      and elevated IL-1alpha, but abrogated airway neutrophilia and reduced mortality,
      mucus obstruction, and emphysema in Scnn1b-Tg mice. Treatment of adult Scnn1b-Tg
      mice with the IL-1R antagonist anakinra had protective effects on neutrophilic
      inflammation and emphysema. Numbers of necrotic airway epithelial cells were
      elevated and correlated with mucus obstruction in patients with CF and chronic
      obstructive pulmonary disease. CONCLUSIONS: Our results support an important role
      of hypoxic epithelial necrosis in the pathogenesis of neutrophilic inflammation
      independent of bacterial infection and suggest IL-1R as a novel target for
      antiinflammatory therapy in CF and potentially other mucoobstructive airway
      diseases.

PMID- 25607240
TI  - Custom-tailored tissue engineered polycaprolactone scaffolds for total disc
      replacement.
AB  - Degeneration of the intervertebral disc (IVD) represents a significant
      musculoskeletal disease burden. Tissue engineering has proposed several
      strategies comprising the use of biodegradable materials to prepare scaffolds
      that can present mechanical properties similar to those of native IVD tissues.
      However, this might be insufficient, since the patient's intervertebral space
      geometry must be replicated to allow for appropriate implant fixation and
      integration. Herein, we propose the use of reverse engineering and rapid
      prototyping techniques with the goal of preparing custom-tailored annulus
      fibrosus scaffolds; these techniques have previously been applied to rabbit
      models. The IVD reverse-engineered architecture was obtained by means of
      microcomputed tomography acquisition and three-dimensional modelling, resulting
      in a computer-aided design (CAD) that replicates the original rabbit IVD. Later,
      a fused deposition-modelling three-dimensional printer was used to produce the
      scaffolds with different geometries provided by the CAD, using polycaprolactone
      (PCL) with 100% infill density. The microstructure of the PCL scaffolds was
      investigated by scanning electron microscopy (SEM), which allowed us to observe
      an adequate fusion adhesion between the layers. The SEM images revealed that, up
      to the point of moderate resolution, the porosities manually designed in the CAD
      model were successfully replicated. The PCL scaffolds' three-dimensional
      architecture was also assessed by means of microcomputed tomography analysis.
      Compressive stiffness was determined using a mechanical testing system. Results
      showed higher values than those of human IVDs (5.9-6.7 kN mm(-1) versus 1.2 kN
      mm(-1), respectively). In vitro studies were performed to investigate the
      possible cytotoxicity of the polycaprolactone scaffolds' leachables. The results
      showed that the custom-tailored PCL scaffolds do not have any deleterious
      cytotoxic effect over annulus fibrosus cells or the mouse lung fibroblast's cell
      line. This study proposed a simple, rapid, and low-cost strategy to fabricate
      custom-tailored annulus fibrosus scaffolds. In the future, this strategy might be
      used in association with nucleus pulposus regeneration strategies to facilitate
      the development of tissue-engineered total disc replacement implants specific to
      each patient, with a goal of full IVD regeneration. 

PMID- 25607241
TI  - Appropriate Tongue Blade Length of the Dingman Mouth Gag for Japanese Pediatric
      Patients With Cleft Palate and Mandibular Micrognathia.
AB  - Objective Our objective is to determine appropriate specifications for smaller
      tongue blade for Japanese pediatric patients with cleft palate (CP) and
      mandibular micrognathia. Patients We investigated 59 patients who underwent
      palatoplasty. Patients were divided into two groups: the micrognathia (MG) group
      consisted of 11 patients and the normognathia (NG) group consisted of 48
      patients. Interventions The following five items were investigated
      retrospectively: (1) gender, (2) cleft type, (3) age at the time of surgery, (4)
      weight at the time of surgery, and (5) distance from the tongue blade base to the
      posterior pharyngeal wall (Dis). Results There was a significant difference (P <
      .01) in age at the time of surgery and in Dis between groups, but not in weight.
      The minimum values were 55 mm for the MG group. As for correlations between age
      and weight at the time of surgery, the P values for the MG and NG groups were
      .993 and .052, respectively. As for correlations between weight at the time of
      surgery and Dis, the P values for the MG and NG groups were .987 and .099,
      respectively. Conclusions It was difficult to predict Dis on the basis of the
      patient's age and weight measured preoperatively. The minimum Dis was 55 mm,
      equal to the length from the base to the tip of the Dingman Mouth Gag tongue
      blade currently in use, suggesting that a tongue blade of approximately 50 mm in
      length, shorter than the current minimum specifications, may be appropriate.

PMID- 25607243
TI  - Appointment availability after increases in Medicaid payments for primary care.
AB  - BACKGROUND: Providing increases in Medicaid reimbursements for primary care, a
      key provision of the Affordable Care Act (ACA), raised Medicaid payments to
      Medicare levels in 2013 and 2014 for selected services and providers. The
      federally funded increase in reimbursements was aimed at expanding access to
      primary care for the growing number of Medicaid enrollees. The reimbursement
      increase expired at the end of 2014 in most states before policymakers had much
      empirical evidence about its effects. METHODS: We measured the availability of
      and waiting times for appointments in 10 states during two periods: from November
      2012 through March 2013 and from May 2014 through July 2014. Trained field staff
      posed as either Medicaid enrollees or privately insured enrollees seeking new
      patient primary care appointments. We estimated state-level changes over time in
      a stable cohort of primary care practices that participated in Medicaid to assess
      whether willingness to provide appointments for new Medicaid enrollees was
      related to the size of increases in Medicaid reimbursements in each state.
      RESULTS: The availability of primary care appointments in the Medicaid group
      increased by 7.7 percentage points, from 58.7% to 66.4%, between the two time
      periods. The states with the largest increases in availability tended to be those
      with the largest increases in reimbursements, with an estimated increase of 1.25
      percentage points in availability per 10% increase in Medicaid reimbursements
      (P=0.03). No such association was observed in the private-insurance group. During
      the same periods, waiting times to a scheduled new-patient appointment remained
      stable over time in the two study groups. CONCLUSIONS: Our study provides early
      evidence that increased Medicaid reimbursement to primary care providers, as
      mandated in the ACA, was associated with improved appointment availability for
      Medicaid enrollees among participating providers without generating longer
      waiting times. (Funded by the Robert Wood Johnson Foundation.).

PMID- 25607244
TI  - Amine-based CO2 capture technology development from the beginning of 2013-a
      review.
AB  - It is generally accepted by the scientific community that anthropogenic CO2
      emissions are leading to global climate change, notably an increase in global
      temperatures commonly referred to as global warming. The primary source of
      anthropogenic CO2 emissions is the combustion of fossil fuels for energy. As
      society's demand for energy increases and more CO2 is produced, it becomes
      imperative to decrease the amount emitted to the atmosphere. One promising
      approach to do this is to capture CO2 at the effluent of the combustion site,
      namely, power plants, in a process called postcombustion CO2 capture.
      Technologies to achieve this are heavily researched due in large part to the
      intuitive nature of removing CO2 from the stack gas and the ease in retrofitting
      existing CO2 sources with these technologies. As such, several reviews have been
      written on postcombustion CO2 capture. However, it is a fast-developing field,
      and the most recent review papers already do not include the state-of-the-art
      research. Notable among CO2 capture technologies are amine-based technologies.
      Amines are well-known for their reversible reactions with CO2, which make them
      ideal for the separation of CO2 from many CO2-containing gases, including flue
      gas. For this reason, this review will cover amine-based technology developed and
      published in and after the year 2013. 

PMID- 25607242
TI  - Red fluorescent zinc oxide nanoparticle: a novel platform for cancer targeting.
AB  - Multifunctional zinc oxide (ZnO) nanoparticles (NPs) with well-integrated
      multimodality imaging capacities have generated increasing research interest in
      the past decade. However, limited progress has been made in developing ZnO NP
      based multimodality tumor-imaging agents. Here we developed novel red fluorescent
      ZnO NPs and described the successful conjugation of 64Cu (t1/2=12.7 h) and
      TRC105, a chimeric monoclonal antibody against CD105, to these ZnO NPs via well
      developed surface engineering procedures. The produced dual-modality ZnO NPs were
      readily applicable for positron emission tomography (PET) imaging and
      fluorescence imaging of the tumor vasculature. Their pharmacokinetics and tumor
      targeting efficacy/specificity in mice bearing murine breast 4T1 tumor were
      thoroughly investigated. ZnO NPs with dual-modality imaging properties can serve
      as an attractive candidate for future cancer theranostics.

PMID- 25607245
TI  - Immediate inferences from quantified assertions.
AB  - We propose a theory of immediate inferences from assertions containing a single
      quantifier, such as: All of the artists are bakers; therefore, some of the bakers
      are artists. The theory is based on mental models and is implemented in a
      computer program, mReasoner. It predicts three main levels of increasing
      difficulty: (a) immediate inferences in which the premise and conclusion have
      identical meanings; (b) those in which the initial mental model of the premise
      yields the correct conclusion; and (c) those in which only an alternative to the
      initial model establishes the correct conclusion. These levels of difficulty were
      corroborated for inferences to necessary conclusions (in a reanalysis of data
      from Newstead, S. E., & Griggs, R. A. (1983). Drawing inferences from quantified
      statements: A study of the square of opposition. Journal of Verbal Learning and
      Verbal Behavior, 22, 535-546), for inferences to modal conclusions, such as, it
      is possible that all of the bakers are artists (Experiment 1), for inferences
      with unorthodox quantifiers, such as, most of the artists (Experiment 2), and for
      inferences about the consistency of pairs of quantified assertions (Experiment
      3). The theory also includes three parameters in a stochastic system that
      predicted quantitative differences in accuracy within the three main sorts of
      inference. 

PMID- 25607246
TI  - Disease Management: The Need for a Focus on Broader Self-Management Abilities and
      Quality of Life.
AB  - The study objective was to investigate long-term effects of disease management
      programs (DMPs) on (1) health behaviors (smoking, physical exercise); (2) self
      management abilities (self-efficacy, investment behavior, initiative taking); and
      (3) physical and mental quality of life among chronically ill patients. The study
      also examined whether (changes in) health behaviors and self-management abilities
      predicted quality of life. Questionnaires were sent to all 5076 patients
      participating in 18 Dutch DMPs in 2010 (T0; 2676 [53%] respondents). Two years
      later (T1), questionnaires were sent to 4350 patients still participating in DMPs
      (1722 [40%] respondents). Structured interviews were held with the 18 DMP project
      leaders. DMP implementation improved patients' health behavior and physical
      quality of life, but mental quality of life and self-management abilities
      declined over time. Changes in patients' investment behavior predicted physical
      quality of life at T1 (P<.001); physical activity, investment behavior (both
      P<.05), and self-efficacy (P<.01) at T0, and changes in self-efficacy and
      investment behavior (both P<.001) predicted patients' mental quality of life at
      T1. The long-term benefits of these DMPs include successful improvement of
      chronically ill patients' health behaviors and physical quality of life. However,
      these programs were not able to improve or maintain broader self-management
      abilities or mental quality of life, highlighting the need to focus on these
      abilities and overall quality of life. As coproducers of care, patients should be
      stimulated and enabled to manage their health and quality of life.

PMID- 25607247
TI  - The Role of Identity Integration in Hedonic Adaptation to a Beneficial Life
      Change: The Example of "Coming Out" for Lesbians and Gay Men.
AB  - After apparently beneficial life changes, people are expected to experience
      elevated well-being. However, research suggests that some individuals adapt
      quickly to change, so their well-being increases little in the long-term. We
      propose this phenomenon is explained by the integration of the changes into
      identity, in interaction with perceived valence of the changes. We hypothesized
      that higher integration would be associated with smaller increases in well-being
      for changes perceived as positive. For changes perceived as negative, higher
      integration would be associated with larger increases in well-being. Lesbians and
      gay men (N = 80) completed a questionnaire on well-being, perceived valence of
      coming out and its integration into identity. Moderated regressions supported the
      hypotheses, revealing the importance of considering identity integration and
      perceived valence in research on adaptation to changes. The results question the
      merits of interventions promoting identity integration. 

PMID- 25607248
TI  - Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through
      autophagy.
AB  - Both apoptosis ("self-killing") and autophagy ("self-eating") are evolutionarily
      conserved processes, and their crosstalk influences anticancer drug sensitivity
      and cell death. However, the underlying mechanism remains unclear. Here, we
      demonstrated that HMGB1 (high mobility group box 1), normally a nuclear protein,
      is a crucial regulator of TNFSF10/TRAIL (tumor necrosis factor [ligand]
      superfamily, member 10)-induced cancer cell death. Activation of PARP1 (poly [ADP
      ribose] polymerase 1) was required for TNFSF10-induced ADP-ribosylation of HMGB1
      in cancer cells. Moreover, pharmacological inhibition of PARP1 activity or
      knockdown of PARP1 gene expression significantly inhibited TNFSF10-induced HMGB1
      cytoplasmic translocation and subsequent HMGB1-BECN1 complex formation.
      Furthermore, suppression of the PARP1-HMGB1 pathway diminished autophagy,
      increased apoptosis, and enhanced the anticancer activity of TNFSF10 in vitro and
      in a subcutaneous tumor model. These results indicate that PARP1 acts as a
      prominent upstream regulator of HMGB1-mediated autophagy and maintains a
      homeostatic balance between apoptosis and autophagy, which provides new insight
      into the mechanism of TNFSF10 resistance. 

PMID- 25607249
TI  - Metabolite profiling of fish skin mucus: a novel approach for minimally-invasive
      environmental exposure monitoring and surveillance.
AB  - The application of 'omics tools to biologically based monitoring and surveillance
      of aquatic environments shows considerable promise for complementing chemical
      monitoring in ecological risk assessments. However, few of the current approaches
      offer the ability to sample ecologically relevant species (e.g., fish) in a way
      that produces minimal impact on the health of the organism(s) under study. In the
      current study we employ liquid chromatography tandem mass spectrometry (LC-MS/MS)
      to assess the potential for skin mucus-based metabolomics for minimally invasive
      sampling of the fathead minnow (FHM; Pimephales promelas). Using this approach we
      were able to detect 204 distinct metabolites in the FHM skin mucus metabolome
      representing a large number of metabolite classes. An analysis of the sex
      specificity of the skin mucus metabolome showed it to be highly sexually
      dimorphic with 72 of the detected metabolites showing a statistically significant
      bias with regard to sex. Finally, in a proof-of-concept fashion we report on the
      use of skin mucus-based metabolomics to assess exposures in male and female
      fathead minnows to an environmentally relevant concentration of bisphenol A, a
      nearly ubiquitous environmental contaminant and an established endocrine active
      chemical. 

PMID- 25607250
TI  - Nonsteroidal anti-inflammatory drugs and the risk for anastomotic failure: a
      report from Washington State's Surgical Care and Outcomes Assessment Program
      (SCOAP).
AB  - IMPORTANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have many physiologic
      effects and are being used more commonly to treat postoperative pain, but recent
      small studies have suggested that NSAIDs may impair anastomotic healing in the
      gastrointestinal tract. OBJECTIVE: To evaluate the relationship between
      postoperative NSAID administration and anastomotic complications. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective cohort study of 13,082 patients
      undergoing bariatric or colorectal surgery at 47 hospitals in Washington State
      from January 1, 2006, through December 31, 2010, using data from the Surgical
      Care and Outcomes Assessment Program linked to the Washington State Comprehensive
      Abstract Reporting System. EXPOSURE: NSAID administration beginning within 24
      hours after surgery. MAIN OUTCOMES AND MEASURES: We used multivariate logistic
      regression modeling to assess the risk for anastomotic complications
      (reoperation, rescue stoma, revision of an anastomosis, and percutaneous drainage
      of an abscess) through 90 days after bariatric and colorectal surgery involving
      anastomoses. RESULTS: Of the 13,082 patients (mean [SD] age, 58.1 [15.8] years;
      60.7% women), 3158 (24.1%) received NSAIDs. The overall 90-day rate of
      anastomotic leaks was 4.3% for all patients (151 patients [4.8%] in the NSAID
      group and 417 patients [4.2%] in the non-NSAID group; P=.16). After risk
      adjustment, NSAIDs were associated with a 24% increased risk for anastomotic leak
      (odds ratio, 1.24 [95% CI, 1.01-1.56]; P=.04). This association was isolated to
      nonelective colorectal surgery, for which the leak rate was 12.3% in the NSAID
      group and 8.3% in the non-NSAID group (odds ratio, 1.70 [95% CI, 1.11-2.68];
      P=.01). CONCLUSIONS AND RELEVANCE: Postoperative NSAIDs were associated with a
      significantly increased risk for anastomotic complications among patients
      undergoing nonelective colorectal resection. To determine the role of NSAIDs in
      colorectal surgery, future evaluations should consider specific formulations, the
      dose effect, mechanism, and other relevant outcome domains, including pain
      control, cardiac complications, and overall recovery.

PMID- 25607251
TI  - RANTES gene polymorphisms are not associated with rheumatoid arthritis and atopic
      dermatitis: a meta-analysis.
AB  - BACKGROUND: A few recent studies have suggested that regulated on activation,
      normal T cell expressed and secreted (RANTES) polymorphisms (-403 G/A, -28C/G)
      are associated with rheumatoid arthritis (RA) and atopic dermatitis (AD).
      However, there still existed studies that did not confirm this correlation.
      OBJECTIVE: The objective of this study was to evaluate the relationships of
      RANTES and RA and AD using a meta-analysis. METHODS: Pubmed, Embase, and Cochrane
      library databases were systemically searched. Data were extracted by two
      independent reviewers, and pooled odds ratio (OR) with 95% confidence interval
      (CI) were calculated. RESULTS: Eight studies were enrolled, including a total of
      548 RA cases and 493 controls of -403G/A, 305 RA cases and 303 controls of 
      28C/G, and 705 AD cases and 578 controls of -403G/A in this meta-analysis. In RA,
      the overall OR and 95% CI of -403A were 1.41, 1.10-1.82 (p = 0.391) and 2.18,
      1.30-3.66 (p = 0.335) in dominant and recessive models, respectively. The overall
      OR and 95% CI of -28G in RA were 1.35, 0.91-2.01 (p = 0.707) and 3.32, 1.29-8.52
      (p = 0.559) in dominant and recessive models, respectively. Moreover, the overall
      OR and 95% CI of -403A in AD were 1.38, 1.08-1.76 (p = 0.421) and 1.06 and 0.65
      1.72 (p = 0.361) in dominant and recessive models, respectively. CONCLUSIONS:
      This meta-analysis showed that RANTES -403G/A and -28C/G were not associated with
      RA and AD.

PMID- 25607252
TI  - Synthesis of the tetracyclic ABCD ring systems of madangamines D-F.
AB  - Synthesis of the tetracyclic cores of madangamines D-F was achieved, featuring a
      reductive radical process from an ethoxycarbonyldichloroacetamide to build the
      morphan nucleus, a Mitsunobu-type aminocyclization toward the common
      diazatricyclic intermediate, and ring-closing metathesis reactions for the
      macrocyclization step leading to the 13- to 15-membered rings. 

PMID- 25607253
TI  - Bilateral lower extremity inflammatory lymphedema in Air Force basic trainees:
      clinical and epidemiologic study of a new disease entity.
AB  - IMPORTANCE: This observational study characterizes a new clinical condition
      identified in 55 military trainees. OBJECTIVE: To determine the incidence and
      underlying cause of bilateral lower extremity inflammatory lymphedema in Air
      Force basic trainees. DESIGN, SETTING, AND PARTICIPANTS: An observational study
      was conducted at Lackland Air Force Base in San Antonio, Texas. Participants
      included 14 243 Air Force basic trainees who entered training between September
      2011 and January 2012 and the 55 trainees (0.4%) who developed bilateral lower
      extremity inflammatory lymphedema that occurred during the 81/2-week basic
      training course. Two modifiable risk factors were evaluated: vaccine reaction and
      newly issued military footwear (combat boots and boot socks). INTERVENTIONS:
      During November 2011, all new trainees wore only white socks and running shoes
      rather than the issued military footwear. During December 2011 and January 2012,
      the scheduled administration of tetanus/diphtheria/acellular pertussis and
      meningococcal vaccines, respectively, was delayed by 1 week for all new trainees.
      A full medical record review was conducted for every confirmed case of bilateral
      lower extremity inflammatory lymphedema. MAIN OUTCOMES AND MEASURES:
      Identification of incident cases, symptom onset, antimicrobial treatment,
      immunization reaction, laboratory studies, specialty referral, and biopsy.
      RESULTS: Fifty-four of the 55 incident cases (98%) of bilateral lower extremity
      inflammatory lymphedema occurred during the first 120 hours of training.
      Alterations in the timing of the military footwear used and selected vaccine
      administration had no effect on the incidence of new cases. Two participants (4%)
      experienced symptom onset before receipt of the vaccines. Oral antimicrobial
      medications were not found to speed symptom resolution compared with conservative
      treatment measures (P = .34). One incident case was diagnosed as leukocytoclastic
      vasculitis by tissue examination. CONCLUSIONS AND RELEVANCE: Multiple training
      related risk factors were ruled out as sources of bilateral lower extremity
      inflammatory lymphedema. Cases are likely secondary to prolonged standing with
      resultant gravity-dependent venous congestion and inflammatory vasculitis. The
      potential roles of undiagnosed venous reflux disease and the military physical
      training environment in these cases remain to be elucidated.

PMID- 25607255
TI  - Statins are potential anticancerous agents (review).
AB  - Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      (HMGCR), which is a rate-limiting enzyme in the mevalonate pathway. The
      pleiotropic effects of statins may be mediated by the inhibition of downstream
      products such as small GTP-binding proteins, Rho, Ras and Rac whose localization
      and function are dependent on isoprenylation. Preclinical studies of statins in
      different cancer cell lines and animal models showed antiproliferative, pro
      apoptotic and anti-invasive effects. Notably, statins showed targeted action in
      cancerous cell lines compared to normal cells. Previous studies have also shown
      the synergistic effects of statins with chemotherapeutic agents and radiotherapy.
      This effect of statins was also observed in chemotherapeutic-resistant tumors.
      Statins were reported to sensitize the cells to radiation by arresting them in
      the late G1 phase of the cell cycle. Similarly, population-based studies also
      demonstrated a chemopreventive and survival benefit of statins in various types
      of cancers. However, this benefit has yet to be proven in clinical trials. The
      inter-individual variation in response to statins may be contributed to many
      genetic and non-genetic factors, including single-nucleotide polymorphisms in
      HMGCR gene and the overexpression of heterogeneous nuclear ribonucleoprotein A1,
      which was reported to reduce HMGCR enzyme activity. However, more studies with
      large phase III randomized controlled trials in cancer patients should be
      conducted to establish the effect of stains in cancer prevention and treatment.

PMID- 25607254
TI  - Total saponins from Albizia julibrissin inhibit vascular endothelial growth
      factor-mediated angiogenesis in vitro and in vivo.
AB  - Dried stem bark from Albizia julibrissin (AJ) is a highly valued Traditional
      Chinese Medicine, which has been shown to suppress tumor growth and angiogenesis.
      Total saponins from AJ (TSAJ) are one of the most bioactive components of AJ
      extract. The present study evaluated the anti-tumor and anti-angiogenic effects
      of TSAJ in vitro and in vivo. The anti-angiogenic activity of TSAJ was
      investigated by measuring the effects on vascular endothelial growth factor
      (VEGF)-induced proliferation, migration and tube formation of Ea.hy926
      endothelial cells in vitro. The expression levels of proteins associated with
      VEGF-induced angiogenesis were determined by western blotting. Furthermore, in
      vivo MatrigelTM plug and H22 hepatoma tumor models were used to verify the anti
      angiogenic effects of TSAJ. The present study demonstrated that TSAJ
      significantly inhibited VEGF-mediated endothelial cell proliferation, migration
      and tube formation of Ea.hy926 cells in vitro. The anti-angiogenic effects of
      TSAJ were modulated by suppression of phosphorylated-(p-) focal adhesion kinase,
      p-Akt, and p-extracellular signal-regulated kinase in the VEGF/VEGF receptor 2
      (R2) signaling pathway. Furthermore, oral administration of TSAJ significantly
      inhibited tumor growth and tumor-induced angiogenesis, as well as the formation
      of functional vessels, in the MatrigelTM plug model. These results suggest that
      TSAJ may be a potential anti-angiogenic agent that targets the VEGF/VEGFR2
      signaling pathway, and inhibits tumor-induced angiogenesis.

PMID- 25607256
TI  - Roles of the human occupant in indoor chemistry.
AB  - Over the last decade, influences of the human occupant on indoor chemistry have
      been investigated in environments ranging from simulated aircraft cabins to
      actual classrooms. We have learned that ozone reacts rapidly with constituents of
      skin surface lipids on exposed skin, hair, and clothing, substantially reducing
      indoor ozone concentrations but increasing airborne levels of mono- and
      bifunctional compounds that contain carbonyl, carboxyl, or alpha-hydroxy ketone
      groups. Moreover, occupants transfer skin oils to and shed skin flakes
      (desquamation) onto indoor surfaces. Evidence for the presence of skin
      flakes/oils has been found in airborne particles, settled dust, and wipes of
      indoor surfaces. These occupant residues are also anticipated to scavenge ozone
      and produce byproducts. Under typical conditions, occupancy is anticipated to
      decrease the net level of oxidants in indoor air. When occupants scavenge ozone,
      the level of SOA derived from ozone/terpene chemistry decreases; the fraction of
      SVOCs in the gas-phase increases, and the fraction associated with airborne
      particles decreases. Occupants also remove organic compounds, including certain
      chemically active species, via bodily intake. Studies reviewed in this paper
      demonstrate the pronounced influences of humans on chemistry within the spaces
      they inhabit and the consequences of these influences on their subsequent
      chemical exposures. 

PMID- 25607257
TI  - Intensive care unit visitation policies in Brazil: firsts steps in Latin America.

PMID- 25607258
TI  - New concepts for bringing urine biochemistry back to clinical practice in the
      intensive care unit.

PMID- 25607259
TI  - Wake up your patients!

PMID- 25607260
TI  - Current insights into severe sepsis in cancer patients.

PMID- 25607261
TI  - Intensive care unit visitation policies in Brazil: a multicenter survey.
AB  - OBJECTIVE: This study aimed to determine which visitation policy was the most
      predominant in Brazilian intensive care units and what amenities were provided to
      visitors. METHODS: Eight hundred invitations were sent to the e-mail addresses of
      intensivist physicians and nurses who were listed in the research groups of the
      Brazilian Association of Intensive Care Network and the Brazilian Research in
      Intensive Care Network. The e-mail contained a link to a 33-item questionnaire
      about the profile of their intensive care unit. RESULTS: One hundred sixty-two
      questionnaires from intensive care units located in all regions of the country,
      but predominantly in the Southeast and South (58% and 16%), were included in the
      study. Only 2.6% of the intensive care units reported having liberal visitation
      policies, while 45.1% of the intensive care units allowed 2 visitation periods
      and 69.1% allowed 31-60 minutes of visitation per period. In special situations,
      such as end-of-life cases, 98.7% of them allowed flexible visitation. About half
      of them (50.8%) did not offer any bedside amenities for visitors. Only 46.9% of
      the intensive care units had a family meeting room, and 37% did not have a
      waiting room. CONCLUSION: Restrictive visitation policies are predominant in
      Brazilian intensive care units, with most of them allowing just two periods of
      visitation per day. There is also a lack of amenities for visitors.

PMID- 25607263
TI  - Adherence to the items in a bundle for the prevention of ventilator-associated
      pneumonia.
AB  - OBJECTIVE: To assess adherence to a ventilator care bundle in an intensive care
      unit and to determine the impact of adherence on the rates of ventilator
      associated pneumonia. METHODS: A total of 198 beds were assessed for 60 days
      using a checklist that consisted of the following items: bed head elevation to 30
      to 45o; position of the humidifier filter; lack of fluid in the ventilator
      circuit; oral hygiene; cuff pressure; and physical therapy. Next, an educational
      lecture was delivered, and 235 beds were assessed for the following 60 days. Data
      were also collected on the incidence of ventilator-acquired pneumonia. RESULTS:
      Adherence to the following ventilator care bundle items increased: bed head
      elevation from 18.7% to 34.5%; lack of fluid in the ventilator circuit from 55.6%
      to 72.8%; oral hygiene from 48.5% to 77.8%; and cuff pressure from 29.8% to
      51.5%. The incidence of ventilator-associated pneumonia was statistically similar
      before and after intervention (p=0.389). CONCLUSION: The educational intervention
      performed in this study increased the adherence to the ventilator care bundle,
      but the incidence of ventilator-associated pneumonia did not decrease in the
      small sample that was assessed.

PMID- 25607262
TI  - Urinary NGAL in patients with and without acute kidney injury in a cardiology
      intensive care unit.
AB  - OBJECTIVE: To assess the diagnostic and prognostic efficacy of urine neutrophil
      gelatinase-associated lipocalin in patients admitted to an intensive care unit.
      METHODS: Longitudinal, prospective cohort study conducted in a cardiology
      intensive care unit. The participants were divided into groups with and without
      acute kidney injury and were followed from admission to the intensive care unit
      until hospital discharge or death. Serum creatinine, urine output and urine
      neutrophil gelatinase-associated lipocalin were measured 24 and 48 hours after
      admission. RESULTS: A total of 83 patients admitted to the intensive care unit
      for clinical reasons were assessed, most being male (57.8%). The participants
      were divided into groups without acute kidney injury (N=18), with acute kidney
      injury (N=28) and with severe acute kidney injury (N=37). Chronic diseases,
      mechanical ventilation and renal replacement therapy were more common in the
      groups with acute kidney injury and severe acute kidney injury, and those groups
      exhibited longer intensive care unit stay and hospital stay and higher mortality.
      Serum creatinine did not change significantly in the group with acute kidney
      injury within the first 24 hours of admission to the intensive care unit,
      although, urine neutrophil gelatinase-associated lipocalin was high in the groups
      with acute kidney injury and severe acute kidney injury (p<0.001). Increased
      urine neutrophil gelatinase-associated lipocalin was associated with death.
      CONCLUSION: An increase in urine neutrophil gelatinase-associated lipocalin
      precedes variations in serum creatinine in patients with acute kidney injury and
      may be associated with death.

PMID- 25607264
TI  - Hemodynamic monitoring in the intensive care unit: a Brazilian perspective.
AB  - OBJECTIVE: In Brazil, there are no data on the preferences of intensivists
      regarding hemodynamic monitoring methods. The present study aimed to identify the
      methods used by national intensivists, the hemodynamic variables they consider
      important, the regional differences, the reasons for choosing a particular
      method, and the use of protocols and continued training. METHODS: National
      intensivists were invited to answer an electronic questionnaire during three
      intensive care events and later, through the Associacao de Medicina Intensiva
      Brasileira portal, between March and October 2009. Demographic data and aspects
      related to the respondent preferences regarding hemodynamic monitoring were
      researched. RESULTS: In total, 211 professionals answered the questionnaire.
      Private hospitals showed higher availability of resources for hemodynamic
      monitoring than did public institutions. The pulmonary artery catheter was
      considered the most trusted by 56.9% of the respondents, followed by
      echocardiograms, at 22.3%. Cardiac output was considered the most important
      variable. Other variables also considered relevant were mixed/central venous
      oxygen saturation, pulmonary artery occlusion pressure, and right ventricular end
      diastolic volume. Echocardiography was the most used method (64.5%), followed by
      pulmonary artery catheter (49.3%). Only half of respondents used treatment
      protocols, and 25% worked in continuing education programs in hemodynamic
      monitoring. CONCLUSION: Hemodynamic monitoring has a greater availability in
      intensive care units of private institutions in Brazil. Echocardiography was the
      most used monitoring method, but the pulmonary artery catheter remains the most
      reliable. The implementation of treatment protocols and continuing education
      programs in hemodynamic monitoring in Brazil is still insufficient.

PMID- 25607265
TI  - Ineffectiveness of using the pressure relief valve technique during cuff
      inflation.
AB  - OBJECTIVE: To test the effectiveness of using a cuff pressure relief valve
      technique to maintain cuff pressure levels within the normal in vitro range
      (Phase 1) in patients admitted to the intensive care unit (Phase 2) and to test
      the reproducibility of the technique using different syringes. METHODS: In Phase
      1, a tracheal tube was inserted into a trachea model. Ten- and 20mL syringes were
      used to inflate the cuff through the tracheal tube. The cuff was slowly and
      steadily inflated until the syringe plunger would move in the opposite direction
      of the application. After the plunger stopped, the cuff pressures were recorded.
      In Phase 2, the same maneuvers for inflating the cuff were performed on 20
      patients using 5, 10, and 20mL syringes and were compared with manometer
      measurements. The intraclass correlation coefficient and Bland-Altman analysis
      were employed to determine the reproducibility and agreement between syringes.
      Data were expressed as medians (interquartile range). RESULTS: There was no
      reproducibility between syringes with an intraclass correlation coefficient
      ranging between -0.33 and 0.8 (p>0.05). The pressures generated with the syringes
      were higher than the pressures generated using a standard manometer: the 5mL
      syringe pressure was 105cmH2O (82.5-120cmH2O), the 10mL syringe pressure was
      69cmH2O (47.5-111.3cmH2O), and the 20mL syringe pressure was 45cmH2O (35
      59.5cmH2O). The Bland-Altman analysis confirmed the large bias and variability
      between the syringes used, compared with the manometer. CONCLUSION: The use of
      syringes is not an effective technique for determining the cuff pressure in
      patients admitted to the intensive care unit.

PMID- 25607266
TI  - Translation and cultural adaptation of the Brazilian Portuguese version of the
      Behavioral Pain Scale.
AB  - OBJECTIVE: The objective of this study was to translate and culturally adapt the
      Behavioral Pain Scale to Brazilian Portuguese and to evaluate the psychometric
      properties of this scale. METHOD: This study was conducted in two phases: the
      Behavioral Pain Scale was translated and culturally adapted to Brazilian
      Portuguese and the psychometric properties of this scale were subsequently
      assessed (reliability and clinical utility). The study sample consisted of 100
      patients who were older than 18 years of age, admitted to an intensive care unit,
      intubated, mechanically ventilated, and subjected or not to sedation and
      analgesia from July 2012 to December 2012. Pediatric and non-intubated patients
      were excluded. The study was conducted at a large private hospital that was
      situated in the city of Sao Paulo (SP). RESULTS: Regarding reproducibility, the
      results revealed that the observed agreement between the two evaluators was
      92.08% for the pain descriptor "adaptation to mechanical ventilation", 88.1% for
      "upper limbs", and 90.1% for "facial expression". The kappa coefficient of
      agreement for "adaptation to mechanical ventilation" assumed a value of 0.740.
      Good agreement was observed between the evaluators with an intraclass correlation
      coefficient of 0.807 (95% confidence interval: 0.727-0.866). CONCLUSION: The
      Behavioral Pain Scale was easy to administer and reproduce. Additionally, this
      scale had adequate internal consistency. The Behavioral Pain Scale was
      satisfactorily adapted to Brazilian Portuguese for the assessment of pain in
      critically ill patients.

PMID- 25607267
TI  - Clinical assessment of the oral cavity of patients hospitalized in an intensive
      care unit of an emergency hospital.
AB  - OBJECTIVE: To describe the oral health status of patients hospitalized in an
      intensive care unit. METHODS: Clinical assessment of the oral cavity was
      performed in 35 patients at two time-points (up to 48 hours after admission and
      72 hours after the first assessment) and recorded in data collection forms. The
      following data were collected: plaque index, condition of the mucosa, presence or
      absence of dental prosthesis, number of teeth present, and tongue coating index.
      RESULTS: The prevalence of nosocomial infection was 22% (eight patients), with
      50% respiratory tract infections. All patients exhibited oral biofilm, and 20
      (57%) showed biofilm visible to the naked eye; tongue coating was present on more
      than two thirds of the tongue in 24 patients (69%) and was thick in most cases. A
      significant increase in plaque index (p=0.007) occurred after 72 hours, although
      the tongue coating index was p<0.001 regarding the area and p=0.5 regarding the
      thickness. CONCLUSION: The plaque and tongue coating indices increased with the
      length of hospital stay at the intensive care unit.

PMID- 25607269
TI  - sRAGE in septic shock: a potential biomarker of mortality.
AB  - OBJECTIVE: To evaluate and understand the clinical implications of the plasma
      levels of a soluble isoform of a receptor for advanced glycation end products
      (sRAGE) in different stages of sepsis. METHODS: Serum sRAGE values in patients
      who were divided into intensive care unit control, severe sepsis, septic shock
      and recovery from septic shock groups were statistically analyzed to assess
      quantity (Kruskal-Wallis), variability (Levine test) and correlation (Spearman
      rank test) with certain inflammatory mediators (IL-1 alpha, IL-6, IL-8, IL-10, IP
      10, G-CSF, MCP-1, IFN-gamma and TNF-alpha). RESULTS: No changes in sRAGE levels
      were observed among the groups; however, the septic shock group showed
      differences in the variability of sRAGE compared to the other groups. A positive
      correlation with all the inflammatory mediators was reported in the septic shock
      group. CONCLUSION: sRAGE levels are associated with worse outcomes in patients
      with septic shock. However, a statistical correlation analysis with other
      proinflammatory cytokines indicated that the pathways leading to those outcomes
      are different depending on the sRAGE levels. Future studies to elucidate the
      pathophysiological mechanisms involving sRAGE in models of sepsis are of great
      clinical importance for the safe handling of this biomarker.

PMID- 25607268
TI  - Septic versus non-septic acute kidney injury in critically ill patients:
      characteristics and clinical outcomes.
AB  - OBJECTIVE: This study aimed to describe and compare the characteristics and
      clinical outcomes of patients with septic and non-septic acute kidney injury.
      METHODS: This study evaluated an open cohort of 117 critically ill patients with
      acute kidney injury who were consecutively admitted to an intensive care unit,
      excluding patients with a history of advanced-stage chronic kidney disease,
      kidney transplantation, hospitalization or death in a period shorter than 24
      hours. The presence of sepsis and in-hospital death were the exposure and primary
      variables in this study, respectively. A confounding analysis was performed using
      logistic regression. RESULTS: No significant differences were found between the
      mean ages of the groups with septic and non-septic acute kidney injury [65.30+/
      21.27 years versus 66.35+/-12.82 years, respectively; p=0.75]. In the septic and
      non-septic acute kidney injury groups, a predominance of females (57.4% versus
      52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%,
      respectively; p=0.49) was observed. Compared with the non-septic patients, the
      patients with sepsis had a higher mean Acute Physiology and Chronic Health
      Evaluation II score [21.73+/-7.26 versus 15.75+/-5.98; p<0.001)] and a higher
      mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure
      (p<0.001) were more common in the non-septic patients. Septic acute kidney injury
      was associated with a greater number of patients who required dialysis (p=0.001)
      and a greater number of deaths (p<0.001); however, renal function recovery was
      more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an
      Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI:
      3.73-25.58) were associated with death in the multivariate analysis. CONCLUSION:
      Sepsis was an independent predictor of death. Significant differences were found
      between the characteristics and clinical outcomes of patients with septic versus
      non-septic acute kidney injury.

PMID- 25607270
TI  - Hemodynamic optimization in severe trauma: a systematic review and meta-analysis.
AB  - OBJECTIVE: Severe trauma can be associated with significant hemorrhagic shock and
      impaired organ perfusion. We hypothesized that goal-directed therapy would confer
      morbidity and mortality benefits in major trauma. METHODS: The MedLine, Embase
      and Cochrane Controlled Clinical Trials Register databases were systematically
      searched for randomized, controlled trials of goal-directed therapy in severe
      trauma patients. Mortality was the primary outcome of this review. Secondary
      outcomes included complication rates, length of hospital and intensive care unit
      stay, and the volume of fluid and blood administered. Meta-analysis was performed
      using RevMan software, and the data presented are as odds ratios for dichotomous
      outcomes and as mean differences (MDs) and standard MDs for continuous outcomes.
      RESULTS: Four randomized, controlled trials including 419 patients were analyzed.
      Mortality risk was significantly reduced in goal-directed therapy-treated
      patients, compared to the control group(OR=0.56, 95%CI: 0.34-0.92). Intensive
      care (MD: 3.7 days 95%CI: 1.06-6.5)and hospital length of stay (MD: 3.5
      days,95%CI: 2.75-4.25) were significantly shorter in the protocol group
      patients.There were no differences in reported total fluid volume or blood
      transfusions administered. Heterogeneity in reporting among the studies prevented
      quantitative analysis of complications. CONCLUSION: Following severe trauma,
      early goal-directed therapy was associated with lower mortality and shorter
      durations of intensive care unit and hospital stays. The findings of this
      analysis should be interpreted with caution due to the presence of significant
      heterogeneity and the small number of the

PMID- 25607271
TI  - Haff disease complicated by multiple organ failure after crayfish consumption: a
      case study.
AB  - Haff disease is a syndrome consisting of unexplained rhabdomyolysis. Patients
      suffering from Haff disease report having eaten fish within 24 hours before the
      onset of illness. Most patients survive and recover quickly. The present study is
      the first report of Haff disease complicated by multiple organ failure after
      crayfish consumption. A 66-year-old Chinese man ate cooked crayfish on the night
      of June 23, 2013. He arrived at our hospital 2 days later and was admitted to the
      intensive care unit. After admission, the patient was diagnosed with Haff disease
      complicated by multiple organ failure. Despite supportive and symptomatic
      treatments, the condition of the patient deteriorated, and he died due to his
      illness. Haff disease is a rare clinical syndrome that is sometimes misdiagnosed.
      Early diagnosis and proper treatment are essential to prevent progression to
      multiple organ failure.

PMID- 25607272
TI  - Varicella associated acute respiratory distress syndrome in an adult patient: an
      example for extracorporeal respiratory support in Brazilian endemic diseases.
AB  - A case of a 30 year-old man presenting with severe systemic chickenpox with
      refractory hypoxemia, central nervous system vasculitis and anuric renal failure
      is described. Ambulance transportation and support using veno-venous
      extracorporeal membrane oxygenation were necessary until the patient recovered.
      Ultimately, the potential use of extracorporeal membrane oxygenation support in
      low-middle income countries to manage common diseases is discussed.

PMID- 25607273
TI  - Is this septic shock? A rare case of distributive shock.
AB  - The authors report a rare case of shock in a patient without significant clinical
      history, admitted to the intensive care unit for suspected septic shock. The
      patient was initially treated with fluid therapy without improvement. A
      hypothesis of systemic capillary leak syndrome was postulated following the
      confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration--a
      combination of three symptoms typical of the disease. The authors discussed the
      differential diagnosis and also conducted a review of the diagnosis and treatment
      of the disease.

PMID- 25607274
TI  - Assistance of inhalation injury victims caused by fire in confined spaces: what
      we learned from the tragedy at Santa Maria.
AB  - On January 2013, a disaster at Santa Maria (RS) due to a fire in a confined space
      caused 242 deaths, most of them by inhalation injury. On November 2013, four
      individuals required intensive care following smoke inhalation from a fire at the
      Memorial da America Latina in Sao Paulo (SP). The present article reports the
      clinical progression and management of disaster victims presenting with
      inhalation injury. Patients ERL and OC exhibited early respiratory failure,
      bronchial aspiration of carbonaceous material, and carbon monoxide poisoning.
      Ventilation support was performed with 100% oxygen, the aspirated material was
      removed by bronchoscopy, and cyanide poisoning was empirically treated with
      sodium nitrite and sodium thiosulfate. Patient RP initially exhibited cough and
      retrosternal burning and subsequently progressed to respiratory failure due to
      upper airway swelling and early-onset pulmonary infection, which were treated
      with protective ventilation and antimicrobial agents. This patient was extubated
      following improvement of edema on bronchoscopy. Patient MA, an asthmatic,
      exhibited carbon monoxide poisoning and bronchospasm and was treated with
      normobaric hyperoxia,bronchodilators, and corticosteroids. The length of stay in
      the intensive care unit varied from four to 10 days, and all four patients
      exhibited satisfactory functional recovery. To conclude, inhalation injury has a
      preponderant role in fires in confined spaces. Invasive ventilation should not be
      delayed in cases with significant airway swelling. Hyperoxia should be induced
      early asa therapeutic means against carbon monoxide poisoning, in addition to
      empiric pharmacological treatment in suspected cases of cyanide poisoning.

PMID- 25607275
TI  - Venous sinus thrombosis in a child with nephrotic syndrome: a case report and
      literature review.
AB  - Nephrotic syndrome is associated with a hypercoagulable state and an increased
      risk of thromboembolic complications. Cerebral venous sinus thrombosis is a rare
      complication of nephrotic syndrome, with few cases described in the literature,
      although the disease may be under-diagnosis. The true incidence of cerebral
      venous sinus thrombosis may be underestimated because many events are
      asymptomatic or are not diagnosed in time. Here, we describe the case of a male
      child, 2 years and 10 months old, with nephrotic syndrome presenting with
      headache, epileptic seizures and sensory inhibition who was diagnosed with
      superior sagittal and transverse sinuses thrombosis. An international literature
      review was performed with a defined search strategy in the PubMed, SciELO and
      Lilacs databases using the terms 'nephrotic syndrome' and 'cerebral sinovenous
      thrombosis'. The diagnosis of venous thrombosis should be considered in any
      patient with nephrotic syndrome who presents with neurological signs and
      symptoms, as early clinical diagnosis promotes favorable outcomes.

PMID- 25607276
TI  - To: High-volume hemofiltration and prone ventilation in subarachnoid hemorrhage
      complicated by severe acute respiratory distress syndrome and refractory septic
      shock.

PMID- 25607277
TI  - To: The use of 2% chlorhexidine gel and toothbrushing for oral hygiene of
      patients receiving mechanical ventilation: effects on ventilator-associated
      pneumonia.

PMID- 25607278
TI  - Antiproliferative Activity of Polyether Antibiotic--Cinchona Alkaloid Conjugates
      Obtained via Click Chemistry.
AB  - A series of eight new conjugates of salinomycin or monensin and Cinchona
      alkaloids were obtained by the Cu(I)-catalysed 1,3-dipolar Huisgen cycloaddition
      (click chemistry) of respective N-propargyl amides of salinomycin or monensin
      with four different Cinchona alkaloid derived azides. In vitro antiproliferative
      activity of these conjugates evaluated against three cancer cell lines (LoVo,
      LoVo/DX, HepG2) showed that four of the compounds exhibited high
      antiproliferative activity (IC50 below 3.00 MUm) and appeared to be less toxic
      and more selective against normal cells than two standard anticancer drugs. 

PMID- 25607279
TI  - Novel methods of inspiratory muscle training via the Test of Incremental
      Respiratory Endurance (TIRE).
AB  - The favorable effects of inspiratory muscle training (IMT) in health and disease
      are becoming much more apparent. A variety of IMT methods exist, but few studies
      have compared IMT methods. The purpose of this article is to review the methods
      and outcomes of the Test of Incremental Respiratory Endurance (TIRE).

PMID- 25607280
TI  - Multidimensional physical activity: an opportunity, not a problem.
AB  - Our research shows that no single metric will reflect an individual's physical
      activity adequately because multiple biologically important dimensions are
      independent and unrelated. We propose that there is an opportunity to exploit
      this multidimensional characteristic of physical activity to improve personalized
      feedback and offer physical activity options and choices that are tailored to an
      individual's needs and preferences. 

PMID- 25607281
TI  - TGF-beta superfamily signaling in muscle and tendon adaptation to resistance
      exercise.
AB  - Numerous studies in muscle and tendon have identified a central role of the
      transforming growth factor-beta (TGF-beta) superfamily of cytokines in the
      regulation of extracellular matrix growth and remodeling, protein degradation,
      and cell proliferation and differentiation. We provide a novel framework for TGF
      beta and myostatin signaling in controlling the coordinated adaptation of both
      skeletal muscle and tendon tissue to resistance training.

PMID- 25607282
TI  - A simple analogy for nervous system plasticity after injury.
AB  - When considering plasticity, the central nervous system can be viewed as a
      building block house. After damage, building components might be lost or loosened
      and may be rearranged by renovation, analogous to neuroplasticity that occurs
      after central nervous system injury. In both scenarios, the location and severity
      of damage will determine the efficacy of renovation/rehabilitation and thus the
      quality of the adapted structure.

PMID- 25607283
TI  - [Study of occupational exposure to magnetic fields among operators of magnetic
      resonance scanning at the Papa Giovanni XXIII Hospital (Bergamo)].
AB  - BACKGROUND: In this study occupational exposure to static magnetic fields of 1T
      and 1.5 T MR scanners installed at Azienda Ospedaliera Papa Giovanni XXIII,
      Bergamo, Italy, was assessed and the results were compared with the limits for
      worker's exposure to static magnetic field currently applicable in Italy
      (Attachment 1 of D.M. 02/08/91). OBJECTIVES: The aim of the study was to assess
      current occupational exposure to static magnetic fields at 1T and 1.5 T MRI
      scanner sites and to predict exposure using the new 3 T MR equipment due to come
      into operation shortly. METHODS: Measurements were performed sampling the static
      magnetic field experienced by workers while carrying out their tasks by means of
      a Hall effect probe. All together, 167 measurements were obtained for 29 workers
      (11 healthcare assistants, 14 radiography technicians and 4 anaesthesiologists).
      RESULTS: The results showed wide variations of occupational exposure parameters
      according to the worker's job, type of procedure and patient's state.
      Nevertheless, it was possible to confirm that the regulatory limits were observed
      in all cases: the time spent by workers in the zone of the magnet room where B >
      200 mT was much shorter than the limit of 1 hour a day prescribed by Italian law
      (D.M 02/08/91) and the maximum time variation of B (dB/dt) was at least 4 times
      lower than the value of 6 T/s taken as the health safety threshold in DM 3/8/93.
      CONCLUSIONS: The data collected suggest that compliance with exposure limits
      prescribed by Italian law will also be met with the new 3 T MR.

PMID- 25607285
TI  - [Workers with Ehlers-Danlos syndrome: indications for health surveillance and
      suitable job assignment].
AB  - BACKGROUNDS: In Europe 23.5% of the working-age population suffers from chronic
      or rare diseases, including Ehlers-Danlos syndrome (EDS), an inherited disorder
      of the connective tissue that frequently leads to impairment also at work.
      OBJECTIVES: We sought to evaluate the impairment of different functional areas in
      EDS subjects, using EDS-Disability Test (EDS-DT) (7 visual analogical scales:
      pain, stiffness, daily activities of life, in the home, outside the home, at
      work, in social relationships). METHODS: We administered the EDS-DT to 50 workers
      with EDS (classic type n=35, hypermobile n=14, vascular n=3) and 150 healthy
      workers (non-EDS). RESULTS: EDS subjects showed higher perceived disability
      (median 29.31 vs 7.22, p< 0.0001) than non-EDS. We observed a trend suggesting
      that the hypermobile type has a higher level of pain (54 vs 42) and work
      impairment (62.5 vs 42.5) (p>0.20), whereas the classic type has greater
      impairment of daily living activities (18.57 vs 11.43) and in the home (34.29 vs
      25.71) (p>0.20). Subjects reporting moderate-to-vigorous occupational physical
      activities (OPA) showed a higher disability level in the work area (p=0.04).
      CONCLUSIONS: People with EDS suffer from chronic pain, impaired quality of life
      and employment difficulties. The hypermobile type seems more compromised in
      functional areas such as pain and work, while the classic type is more
      compromised in daily routine and home activities. The employment section was more
      impaired for EDS subjects who perform tasks with greater physical effort.

PMID- 25607284
TI  - Occupational accidents among attendants inside hyperbaric chambers in France.
AB  - INTRODUCTION: The purpose of the study was to assess the number of accidents
      among staff employed in the operation of hyperbaric chambers in France. MATERIALS
      AND METHODS: A retrospective study using a questionnaire was carried out on
      occupational accidents in France between 2005 and 2011. RESULTS: 12 (46%) centres
      participated in the study, representing 73 subjects. The mean age was 43.5 years
      (SD=9.73). They had worked in hyperbaric chambers for 9.8 years on average
      (SD=7.7). The average number of hyperbaric sessions was 198.3 per subject
      (SD=174.25), for a total of 8.072 hyperbaric sessions; 27% of the subjects
      reported that they had at least one accident during the study period. In all, 30
      accidents were reported: 3 blood exposures, 4 accidents related to patient
      handling, 20 hyperbaric accidents; 3 other accidents. Of the hyperbaric
      accidents, 2 (10%) involved decompression sicknesses with cutaneous symptoms, 3
      (15%) decompression illness (DCI), 14 (70%) ear traumatisms, 1 (5%) dental
      accident. The incidences were 372 per 100,000 sessions in hyperbaric chambers
      (SHC) for all accidents, 248 per 100,000 SHC for hyperbaric accidents and 173 per
      100,000 SHC for ENT barotraumas. CONCLUSION: The accidents involving staff
      operating hyperbaric chambers were mainly ear traumatisms..

PMID- 25607286
TI  - [Results of an alcohol breath-test campaign in a sample of construction site
      workers in the Umbria region].
AB  - OBJECTIVE: The purpose of the research was to evaluate the respect of the
      regulation on the prohibition of alcohol consumption in the building sector
      through an alcohol breath test campaign, and to acquire information on the
      alcohol consumption by the contractors. METHODS: In the course of the
      investigation which covered the period 2011-2013, in a sample of construction, it
      was decided to access with verification of the presence of alcoholic beverages,
      administration workers to an anonymous questionnaire on alcohol consumption,
      execution of alcohol breath test. RESULTS: The reached population consisted in
      1635 subjects, 1040 of which Italians and 595 foreigners; the consumers of at
      least 0,5 AU/die resulted being 354 among Italians and 250 among foreigners
      (p<0,05), the main occasion of consumption was observed being the meal for 39,8%
      of subjects; wine, followed by beer, were recorded as the most consumed
      beverages. The great majority of subjects, 1340, declared being aware of the
      regulation on the prohibition of alcohol consumption and only a minimum part of
      it, 42 subjects, declared having occasionally consumed alcoholic beverages for
      more than 6 AU, or having driven a car, 3 subjects, after having consumed at
      least 2 AU, or having had interviews, 115 subjects, about alcohol consumption
      with healthcare operators. The alcohol test results only marked 91 cases (5,6%)
      of positiveness with values mostly confined to 0,2 g/l, and the distribution of
      positive tests resulted substantially overlapping (p>0,05) between foreigners and
      Italians. Notwithstanding, among the negative subjects, 9% declared having
      consumed alcoholics during the meal immediately preceding the work shift; all
      this underlining a sound dangerous behaviour. A behaviour which may easily escape
      to an alcohol metric test, considering the relationship between the timing of the
      last alcohol consumption, the quantity assumed, the test timing and its result.
      CONCLUSIONS: The authors conclude pointing out how, in the studied sector, there
      certainly is a great tendency to respect the regulation on the prohibition of
      alcohol consumption, and how there is a reliable modification with regards to
      alcohol among the behavioural models traditionally allocated to building
      contractors, with a strong reduction of consumption as in working as in non
      working hours. Notwithstanding, the authors may want to underline the persistency
      of dangerous behaviours worthy promotion, information and education actions.
      Besides, they advise and wish for additional interventions by the legislator,
      directed to better define the boundaries of the prohibition and impose in such
      boundaries an alcohol test level equal to 0 during the working hours.

PMID- 25607287
TI  - [Industrial first aid equipment: a historical analysis (1840-1914) ].
AB  - Even if references to the tools required to intervene after an accident can be
      found in the works of Bernardino Ramazzini (1633-1714) or Johann Peter Frank
      (1745-1821), it was only with the development of industrial manufacturing that
      the need to study means to prevent and intervene in cases of accident became
      evident. In October 1894 the III Congres International des Accidents du Travail
      et des Assurances Sociales was held in Milan. The following year, the Milanese
      trade union movement acknowledged the necessity to address the problem of
      industrial accidents. In 1896 the Association for Medical Assistance in 
      Industrial Accidents was founded in Milan. A specific medical institute was set
      up, appropriate first aid tools were collected and first aid rooms in the main
      Milanese factories were inaugurated. Nevertheless, few data seem to be available
      regarding the manufacture and use of this equipment in industry. We analyzed more
      than fifty catalogs of European industrial products, between 1843 and 1914, to
      study the evolution of first aid equipment for industrial use. They reflect and
      attest to the evolution of medicine and surgery, although some models seem to be
      related to certain industrial categories (railways, electrical appliances), some
      were similar to ordinary first aid boxes, others were strictly related to
      surgery; some could only be used by physicians, and others only by workers.
      Identification, conservation, and reappraisal of these tools is essential for
      historians of occupational health because these objects were normally not
      preserved. The catalogues of industrial production are also precious sources,
      since they are rarely preserved in public libraries and deserve to be used for
      historical studies. 

PMID- 25607288
TI  - [The assessment of psychosocial risk: only "work-related stress" or something
      else?].

PMID- 25607289
TI  - [Remembering Bernardino Ramazzini on the occasion of the tercentenary of his
      death (1714-2014): celebrations in Padua, San Paulo, Brazil and Modena].

PMID- 25607290
TI  - [Recognized error in a [mathematical] sign in the solution of the Peto formula].

PMID- 25607291
TI  - Environmental epidemiology: What's at stake: open issues and methodologies --
      report from the 26th Annual Conference of the International Society for
      Environmental Epidemiology (ISEE).
AB  - At the end of last August, the University of Washington (UW) in Seattle welcomed
      over 1,100 attendees at the 26th Annual ISEE Conference - "From Local to Global:
      Advancing Science for Policy in Environmental Health"...

PMID- 25607292
TI  - [Recognized error in a [mathematical] sign in the solution of the Peto formula].

PMID- 25607295
TI  - Total internal reflection-based planar waveguide solar concentrator with
      symmetric air prisms as couplers.
AB  - We present a waveguide coupling approach for planar waveguide solar concentrator.
      In this approach, total internal reflection (TIR)-based symmetric air prisms are
      used as couplers to increase the coupler reflectivity and to maximize the optical
      efficiency. The proposed concentrator consists of a line focusing cylindrical
      lens array over a planar waveguide. The TIR-based couplers are located at the
      focal line of each lens to couple the focused sunlight into the waveguide. The
      optical system was modeled and simulated with a commercial ray tracing software
      (Zemax). Results show that the system used with optimized TIR-based couplers can
      achieve 70% optical efficiency at 50 * geometrical concentration ratio, resulting
      in a flux concentration ratio of 35 without additional secondary concentrator. An
      acceptance angle of +/- 7.5 degrees  is achieved in the x-z plane due to the use
      of cylindrical lens array as the primary concentrator. 

PMID- 25607297
TI  - Hybrid tandem solar cell enhanced by a metallic hole-array as the intermediate
      electrode.
AB  - A metallic hole-array structure was inserted into a tandem solar cell structure
      as an intermediate electrode, which allows a further fabrication of a novel and
      efficient hybrid organic-inorganic tandem solar cell. The inserted hole-array
      layer reflects the higher-energy photons back to the top cell, and transmits
      lower-energy photons to the bottom cell via the extraordinary optical
      transmission (EOT) effect. In this case light absorption in both top and bottom
      subcells can be simultaneously enhanced via both structural and material
      optimizations. Importantly, this new design could remove the constraints of
      requiring lattice-matching and current-matching between the used two cascaded
      subcells in a conventional tandem cell structure, and therefore, the tunnel
      junction could be no longer required. As an example, a novel PCBM/CIGS tandem
      cell was designed and investigated. A systematic modeling study was made on the
      structural parameter tuning, with the period ranging from a few hundreds
      nanometers to over one micrometer. Surface plasmon polaritons, magnetic plasmon
      polaritons, localized surface plasmons, and optical waveguide modes were found to
      participate in the EOT and the light absorption enhancement. Impressively, more
      than 40% integrated power enhancement can be achieved in a variable structural
      parameter range. 

PMID- 25607298
TI  - Microstructured porous ZnO thin film for increased light scattering and improved
      efficiency in inverted organic photovoltaics.
AB  - Microstructured porous zinc oxide (ZnO) thin film was developed and demonstrated
      as an electron selective layer for enhancing light scattering and efficiency in
      inverted organic photovoltaics. High degree of porosity was induced and
      controlled in the ZnO layer by incorporation of polyethylene glycol (PEG) organic
      template. Scanning electron microscopy, contact angle and absorption measurements
      prove that the ZnO:PEG ratio of 4:1 is optimal for the best performance of porous
      ZnO. Ensuring sufficient pore-filling, the use of porous ZnO leads to a marked
      improvement in device performance compared to non-porous ZnO, with 35% increase
      in current density and 30% increase in efficiency. Haze factor studies indicate
      that the performance improvement can be primarily attributed to the improved
      light scattering enabled by such a highly porous structure. 

PMID- 25607299
TI  - Pyramidal surface textures for light trapping and antireflection in perovskite-on
      silicon tandem solar cells.
AB  - Perovskite-on-silicon tandem solar cells show potential to reach > 30% conversion
      efficiency, but require careful optical control. We introduce here an effective
      light-management scheme based on the established pyramidal texturing of
      crystalline silicon cells. Calculations show that conformal deposition of a thin
      film perovskite solar cell directly onto the textured front surface of a high
      efficiency silicon cell can yield front surface reflection losses as low as
      0.52mA/cm(2). Combining this with a wavelength-selective intermediate reflector
      between the cells additionally provides effective light-trapping in the high
      bandgap top cell, resulting in calculated absolute efficiency gains of 2 - 4%.
      This approach provides a practical and effective method to adapt existing high
      efficiency silicon cell designs for use in tandem cells, with conversion
      efficiencies approaching 35%.

PMID- 25607300
TI  - Silicon nanodisk array design for effective light trapping in ultrathin c-Si.
AB  - The use of ultrathin c-Si (crystalline silicon) wafers thinner than 20 MUm for
      solar cells is a very promising approach to realize dramatic reduction in cell
      cost. However, the ultrathin c-Si requires highly effective light trapping to
      compensate optical absorption reduction. Conventional texturing in micron scale
      is hardly applicable to the ultrathin c-Si wafers; thus, nano scale texturing is
      demanded. In general, nanotexturing is inevitably accompanied by surface area
      enlargements, which must be minimized in order to suppress surface recombination
      of minority carriers. In this study, we demonstrate using optical simulations
      that periodic c-Si nanodisk arrays of short heights less than 200 nm and optimal
      periods are very useful in terms of light trapping in the ultrathin c-Si wafers
      while low surface area enlargements are maintained. Double side texturing with
      the nanodisk arrays leads to over 90% of the Lambertian absorption limit while
      the surface area enlargement is kept below 1.5. 

PMID- 25607301
TI  - Effect of Auger recombination and leakage on the droop in InGaN/GaN quantum well
      LEDs.
AB  - We investigate the effect of the epitaxial structure and the acceptor doping
      profile on the efficiency droop in InGaN/GaN LEDs by the physics based simulation
      of experimental internal quantum efficiency (IQE) characteristics. The device
      geometry is an integral part of our simulation approach. We demonstrate that even
      for single quantum well LEDs the droop depends critically on the acceptor doping
      profile. The Auger recombination was found to increase stronger than with the
      third power of the carrier density and has been found to dominate the droop in
      the roll over zone of the IQE. The fitted Auger coefficients are in the range of
      the values predicted by atomistic simulations. 

PMID- 25607302
TI  - Mesoscale modeling of photoelectrochemical devices: light absorption and carrier
      collection in monolithic, tandem, Si|WO3 microwires.
AB  - We analyze mesoscale light absorption and carrier collection in a tandem junction
      photoelectrochemical device using electromagnetic simulations. The tandem device
      consists of silicon (E(g,Si) = 1.1 eV) and tungsten oxide (E(g,WO3) = 2.6 eV) as
      photocathode and photoanode materials, respectively. Specifically, we
      investigated Si microwires with lengths of 100 um, and diameters of 2 um, with a
      7 um pitch, covered vertically with 50 um of WO3 with a thickness of 1 um. Many
      geometrical variants of this prototypical tandem device were explored. For
      conditions of illumination with the AM 1.5G spectra, the nominal design resulted
      in a short circuit current density, J(SC), of 1 mA/cm(2), which is limited by the
      WO3 absorption. Geometrical optimization of photoanode and photocathode shape and
      contact material selection, enabled a three-fold increase in short circuit
      current density relative to the initial design via enhanced WO3 light absorption.
      These findings validate the usefulness of a mesoscale analysis for ascertaining
      optimum optoelectronic performance in photoelectrochemical devices.

PMID- 25607303
TI  - Enhanced light output power of thin film GaN-based high voltage light-emitting
      diodes.
AB  - The characteristics of high-voltage light-emitting diodes (HVLEDs) consisting of
      a 64-cell LED array were investigated by employing various LED structures. Two
      types of HVLED were examined: a standard HVLED with a single roughened indium tin
      oxide (ITO) surface grown on a sapphire substrate and a thin-film HVLED (TF
      HVLED) with a roughened n-GaN and ITO double side transferred to a mirror/silicon
      substrate. At an injection current of 24 mA, the output powers of the HVLEDs
      fabricated using a sapphire substrate and those fabricated using a mirror/silicon
      substrate were 170 and 216 mW, respectively. Because the TF-HVLED exhibited
      improved thermal dissipation and light extraction, it produced a greater output
      power than the HVLED fabricated using the sapphire substrate did. 

PMID- 25607304
TI  - Influence of black silicon surfaces on the performance of back-contacted back
      silicon heterojunction solar cells.
AB  - The influence of different black silicon (b-Si) front side textures prepared by
      inductively coupled reactive ion etching (ICP-RIE) on the performance of back
      contacted back silicon heterojunction (BCB-SHJ) solar cells is investigated in
      detail regarding their optical performance, black silicon surface passivation and
      internal quantum efficiency. Under optimized conditions the effective minority
      carrier lifetime measured on black silicon surfaces passivated with Al(2)O(3) can
      be higher than lifetimes measured for the SiO(2)/SiN(x) passivation stack used in
      the reference cells with standard KOH textures. However, to outperform the
      electrical current of silicon back-contact cells, the black silicon back-contact
      cell process needs to be optimized with aspect to chemical and thermal stability
      of the used dielectric layer combination on the cell.

PMID- 25607305
TI  - Slim planar apparatus for converting LED light into collimated polarized light
      uniformly emitted from its top surface.
AB  - This study proposes a slim planar apparatus for converting nonpolarized light
      from a light-emitting diode (LED) into an ultra-collimated linearly polarized
      beam uniformly emitted from its top surface. The apparatus was designed based on
      a folded-bilayer configuration comprising a light-mixing collimation element,
      polarization conversion element, and polarization-preserving light guide plate
      (PPLGP) with an overall thickness of 5 mm. Moreover, the apparatus can be
      extended transversally by connecting multiple light-mixing collimation elements
      and polarization conversion elements in a side-by-side configuration to share a
      considerably wider PPLGP, so the apparatus can have theoretically unlimited
      width. The simulation results indicate that the proposed apparatus is feasible
      for the maximal backlight modules in 39-inch liquid crystal panels. In the case
      of an apparatus with a 480 * 80 mm emission area and two 8-lumen LED light
      sources, the average head-on polarized luminance and spatial uniformity over the
      emission area was 5000 nit and 83%, respectively; the vertical and transverse
      angular distributions of the emitting light were only 5 degrees  and 10 degrees ,
      respectively. Moreover, the average degree of polarization and energy efficiency
      of the apparatus were 82% and 72%, respectively. As compared with the high
      performance ultra-collimated nonpolarized backlight module proposed in our prior
      work, not only did the apparatus exhibit outstanding optical performance, but
      also the highly polarized light emissions actually increased the energy
      efficiency by 100%. 

PMID- 25607306
TI  - Two-step design method for highly compact three-dimensional freeform optical
      system for LED surface light source.
AB  - Designing an illumination system for a surface light source with a strict
      compactness requirement is quite challenging, especially for the general three
      dimensional (3D) case. In accordance with the two key features of an expected
      illumination distribution, i.e., a well-controlled boundary and a precise
      illumination pattern, a two-step design method is proposed in this paper for
      highly compact 3D freeform illumination systems. In the first step, a target
      shape scaling strategy is combined with an iterative feedback modification
      algorithm to generate an optimized freeform optical system with a well-controlled
      boundary of the target distribution. In the second step, a set of selected radii
      of the system obtained in the first step are optimized to further improve the
      illuminating quality within the target region. The method is quite flexible and
      effective to design highly compact optical systems with almost no restriction on
      the shape of the desired target field. As examples, three highly compact freeform
      lenses with ratio of center height h of the lens and the maximum dimension D of
      the source <= 2.5:1 are designed for LED surface light sources to form a uniform
      illumination distribution on a rectangular, a cross-shaped and a complex cross
      pierced target plane respectively. High light control efficiency of eta > 0.7 as
      well as low relative standard illumination deviation of RSD < 0.07 is obtained
      simultaneously for all the three design examples. 

PMID- 25607307
TI  - Light diffusing effects of nano and micro-structures on OLED with microcavity.
AB  - We examined the light diffusing effects of nano and micro-structures on
      microcavity designed OLEDs. The results of FDTD simulations and experiments
      showed that the pillar shaped nano-structure was more effective than the concave
      micro-structure for light diffusing of microcavity OLEDs. The sharp luminance
      distribution of the microcavity OLED was changed to near Lambertian luminance
      distribution by the nano-structure, and light diffusing effects increased with
      the height of the nano-structure. Furthermore, the nano-structure has advantages
      including light extraction of the substrate mode, reproducibility of
      manufacturing process, and minimizing pixel blur problems in an OLED display
      panel. The nano-structure is a promising candidate for a light diffuser,
      resolving the viewing angle problems in microcavity OLEDs. 

PMID- 25607308
TI  - Enhancing photovoltaic output power by 3-band spectrum-splitting and
      concentration using a diffractive micro-optic.
AB  - We report the enhancement of photovoltaic output power by separating the incident
      spectrum into 3 bands, and concentrating these bands onto 3 different
      photovoltaic cells. The spectrum-splitting and concentration is achieved via a
      thin, planar micro-optical element that demonstrates high optical efficiency over
      the entire spectrum of interest. The optic (which we call a polychromat) was
      designed using a modified version of the direct-binary-search algorithm. The
      polychromat was fabricated using grayscale lithography. Rigorous optical
      characterization demonstrates excellent agreement with simulation results.
      Electrical characterization of the solar cells made from GaInP, GaAs and Si
      indicate increase in the peak output power density of 43.63%, 30.84% and 30.86%,
      respectively when compared to normal operation without the polychromat. This
      represents an overall increase of 35.52% in output power density. The potential
      for cost-effective large-area manufacturing and for high system efficiencies
      makes our approach a strong candidate for low cost solar power. 

PMID- 25607309
TI  - Engineered surface scatterers in edge-lit slab waveguides to improve light
      delivery in algae cultivation.
AB  - Most existing photobioreactors do a poor job of distributing light uniformly due
      to shading effects. One method by which this could be improved is through the use
      of internal wave-guiding structures incorporating engineered light scattering
      schemes. By varying the density of these scatterers, one can control the spatial
      distribution of light inside the reactor enabling better uniformity of
      illumination. Here, we compare a number of light scattering schemes and evaluate
      their ability to enhance biomass accumulation. We demonstrate a design for a
      gradient distribution of surface scatterers with uniform lateral scattering
      intensity that is superior for algal biomass accumulation, resulting in a 40%
      increase in the growth rate. 

PMID- 25607310
TI  - Seebeck nanoantennas for the detection and characterization of infrared
      radiation.
AB  - Arrays of metallic thermocouples in the shape of spiral nanoantennas are proposed
      as infrared detectors, which use the thermoelectric properties of the metallic
      interfaces to generate electrical DC signals. The responsivity of these types of
      antennas is evaluated from both theoretical and numerical perspectives pointing
      out its potential as infrared sensors. Moreover, the same structures can be used
      to characterize the state of polarization of the optical near fields with a
      spatial resolution comparable to the wavelength. 

PMID- 25607311
TI  - Polarization insensitive infrared absorbing behaviour of one-dimensional
      multilayer stack: a fractal approach.
AB  - The control and tailoring of infrared absorbance/emittance is a crucial task for
      all those applications involving thermal radiation management and detection. We
      theoretically investigated the peculiar absorbing/emitting behaviour of pre
      fractal Cantor multilayers, in order to design a polarization-insensitive
      multilayer stack absorbing over a wide angular lobe in the mid wavelength
      infrared range (8-10 MUm). Using transfer matrix method, we explored the spectral
      properties arising from both the material and the geometrical dispersion. We
      considered several combinations of the constituent materials: SiO2 was combined
      with TiO2 and Si, respectively.

PMID- 25607312
TI  - Size dependence of silica nanospheres embedded in 385 nm ultraviolet light
      emitting diodes on a far-field emission pattern.
AB  - We demonstrate that the use of silica nanospheres (SNs) with sizes close to the
      emission wavelength of light-emitting diodes (LEDs) can enhance the light output
      power and manipulate the far-field emission pattern. Near-ultraviolet (NUV)-LEDs
      grown on a patterned sapphire substrate embedded with 300 nm SNs show a three
      times higher light output power than that without SNs, when measured through the
      top side. For far-field emission measurements, the LEDs embedded with 300 nm SNs
      show the significant increase of front emission due to the improved crystal
      quality of epitaxial films as well as the increase of Mie scattering effect of
      SNs. These experimental results indicate the important role of the size of
      embedded SNs in enhancing the light output power for NUV-LEDs. 

PMID- 25607313
TI  - Enhancement of the evanescent wave coupling effect in a sub-wavelength-sized
      GaAs/AlGaAs ridge structure by low-refractive-index surface layers.
AB  - We have investigated the three-dimensional emission patterns of GaAs/AlGaAs ridge
      structures with a sub-wavelength-sized top-flat facet by angle-resolved
      photoluminescence (PL). We found that the integrated PL intensity, and hence the
      light-extraction efficiency, can be enhanced by about 34% just by covering the
      ridge surface with a thin SiO2 layer. A double-coupling effect of evanescent
      waves that occurs at both the semiconductor-SiO2 and SiO2-air interfaces is
      suggested to be responsible for the improvement, based on a finite-difference
      time-domain simulation of the electromagnetic field around the ridge top.

PMID- 25607314
TI  - Two-axis tracking using translation stages for a lens-to-channel waveguide solar
      concentrator.
AB  - A two-axis tracking scheme designed for <250x concentration realized by a single
      axis mechanical tracker and a translation stage is discussed. The translation
      stage is used for adjusting positions for seasonal sun movement. It has two
      dimensional x-y tracking instead of horizontal movement x-only. This tracking
      method is compatible with planar waveguide solar concentrators. A prototype
      system with 50x concentration shows >75% optical efficiency throughout the year
      in simulation and >65% efficiency experimentally. This efficiency can be further
      improved by the use of anti-reflection layers and a larger waveguide refractive
      index. 

PMID- 25607315
TI  - Resonance-induced absorption enhancement in colloidal quantum dot solar cells
      using nanostructured electrodes.
AB  - The application of nanostructured indium-doped tin oxide (ITO) electrodes as
      diffraction gratings for light absorption enhancement in colloidal quantum dot
      solar cells is numerically investigated using finite-difference time-domain
      (FDTD) simulation. Resonant coupling of the incident diffracted light with
      supported waveguide modes in light absorbing layer at particular wavelengths
      predicted by grating far-field projection analysis is shown to provide superior
      near-infrared light trapping for nanostructured devices as compared to the planar
      structure. Among various technologically feasible nanostructures, the two
      dimensional nano-branch array is demonstrated as the most promising polarization
      independent structure and proved to be able to maintain its performance despite
      structural imperfections common in fabrication. 

PMID- 25607316
TI  - Monolithic integration of GaN-based light-emitting diodes and metal-oxide
      semiconductor field-effect transistors.
AB  - In this study, we report a novel monolithically integrated GaN-based light
      emitting diode (LED) with metal-oxide-semiconductor field-effect transistor
      (MOSFET). Without additionally introducing complicated epitaxial structures for
      transistors, the MOSFET is directly fabricated on the exposed n-type GaN layer of
      the LED after dry etching, and serially connected to the LED through standard
      semiconductor-manufacturing technologies. Such monolithically integrated
      LED/MOSFET device is able to circumvent undesirable issues that might be faced by
      other kinds of integration schemes by growing a transistor on an LED or vice
      versa. For the performances of resulting device, our monolithically integrated
      LED/MOSFET device exhibits good characteristics in the modulation of gate voltage
      and good capability of driving injected current, which are essential for the
      important applications such as smart lighting, interconnection, and optical
      communication. 

PMID- 25607317
TI  - Surface plasmon-enhanced nanoporous GaN-based green light-emitting diodes with
      Al2O3 passivation layer.
AB  - A surface plasmon (SP)-enhanced nanoporous GaN-based green LED based on top-down
      processing technology has been successfully fabricated. This SP-enhanced LED
      consists of nanopores passing through the multiple quantum wells (MQWs) region,
      with Ag nanorod array filled in the nanopores for SP-MQWs coupling and thin
      Al(2)O(3) passivation layer for electrical protection. Compared with nanoporous
      LED without Ag nanorods, the electroluminescence (EL) peak intensity for the SP
      enhanced LED was greatly enhanced by 380% and 220% at an injection current
      density of 1 and 20A/cm(2), respectively. Our results show that the increased EL
      intensity is mainly attributed to the improved internal quantum efficiency of LED
      due to the SP coupling between Ag nanorods and MQWs.

PMID- 25607318
TI  - Role of spectral non-idealities in the design of solar thermophotovoltaics.
AB  - To bridge the gap between theoretically predicted and experimentally demonstrated
      efficiencies of solar thermophotovoltaics (STPVs), we consider the impact of
      spectral non-idealities on the efficiency and the optimal design of STPVs over a
      range of PV bandgaps (0.45-0.80 eV) and optical concentrations (1-3,000x). On the
      emitter side, we show that suppressing or recycling sub-bandgap radiation is
      critical. On the absorber side, the relative importance of high solar absorptance
      versus low thermal emittance depends on the energy balance. Both results are well
      described using dimensionless parameters weighting the relative power density
      above and below the cutoff wavelength. This framework can be used as a guide for
      materials selection and targeted spectral engineering in STPVs. 

PMID- 25607319
TI  - Self-organized nanoparticle photolithography for two-dimensional patterning of
      organic light emitting diodes.
AB  - We report a new simple and inexpensive sub-micrometer two dimensional patterning
      technique. This technique combines a use of a photomask featured with self
      organized particles in the micro- to nano-meter size range and a photoresist
      covered substrate. The photomask was prepared by depositing monodispersed silicon
      dioxide (SiO(2))- or polystyrene- spheres on a quartz substrate to form a close
      packed pattern. The patterning technique can be realized in two configurations: a
      hard-contact mode or a soft-contact mode. In the first configuration, each sphere
      acts as a micro ball-lens that focuses light and exposes the photoresist
      underneath the sphere. The developed pattern therefore reproduces exactly the
      same spatial arrangement as the close-packed spheres but with a feature size of
      developed hole smaller than the diameter of the sphere. In the soft-contact mode,
      an air gap of few micrometers thick is introduced between the 2D array of self
      organized spheres and the photoresist-covered substrate. In this case, a phase
      mask behavior is obtained which results in an exposure area with a lattice period
      being half of the sphere diameter. A 2D lattice structure with period and feature
      size of a developed hole as small as 750 nm and 420 nm, respectively, was
      realized in this configuration. We further applied this technique to host the
      deposition of organic films into the 2D nanostructure and demonstrated the
      realization of green and red nano-structured OLEDs.

PMID- 25607320
TI  - Binary phase shift keying on orthogonal carriers for multi-channel CO2 absorption
      measurements in the presence of thin clouds.
AB  - A new modulation technique for Continuous Wave (CW) Lidar is presented based on
      Binary Phase Shift Keying (BPSK) using orthogonal carriers closely spaced in
      frequency, modulated by Maximum Length (ML) sequences, which have a theoretical
      autocorrelation function with no sidelobes. This makes it possible to conduct
      multi-channel atmospheric differential absorption measurements in the presence of
      thin clouds without the need for further processing to remove errors caused by
      sidelobe interference while sharing the same modulation bandwidth. Flight tests
      were performed and data were collected using both BPSK and linear swept frequency
      modulation. This research shows there is minimal or no sidelobe interference in
      the presence of thin clouds for BPSK compared to linear swept frequency with
      significant sidelobe levels. Comparisons between of CO(2) optical depth Signal to
      Noise (SNR) between the BPSK and linear swept frequency cases indicate a 21% drop
      in SNR for BPSK experimentally using the instrument under consideration.

PMID- 25607321
TI  - Multi-objective genetic algorithm for the optimization of a flat-plate solar
      thermal collector.
AB  - We present a multi-objective genetic algorithm we developed for the optimization
      of a flat-plate solar thermal collector. This collector consists of a waffle
      shaped Al substrate with NiCrOx cermet and SnO(2) anti-reflection conformal
      coatings. Optimal geometrical parameters are determined in order to (i) maximize
      the solar absorptance alpha and (ii) minimize the thermal emittance epsilon. The
      multi-objective genetic algorithm eventually provides a whole set of Pareto
      optimal solutions for the optimization of alpha and epsilon, which turn out to be
      competitive with record values found in the literature. In particular, a solution
      that enables alpha = 97.8% and epsilon = 4.8% was found.

PMID- 25607322
TI  - Advance care planning in palliative care: a national survey of health
      professionals and service managers.
AB  - OBJECTIVE: To identify the attitudes, knowledge and practices regarding advance
      care planning (ACP) in palliative care. METHODS: A nationwide online survey was
      distributed to Australian palliative care services associated with the Palliative
      Care Outcomes Collaboration (n=105). Seventy-three health professionals (HPs) and
      59 service managers completed the survey. RESULTS: Regarding ACP, 51% of service
      managers reported relevant policies and procedures were in place in their service
      and 44% included ACP in job descriptions. Most HPs were confident in undertaking
      ACP, including initiating discussions with patients and complying with documents;
      however, only 44% reported receiving ACP specific training. Although 58% of HPs
      reported having conversations about ACP with more than 11 patients in the past 6
      months, only 44% of managers report that it is offered to most patients. Thirty
      per cent of HPs were aware of others not adhering to patient wishes in the past 6
      months and only 43% of HPs (and 37% of managers) believed ACP is done well within
      their service. CONCLUSIONS: This first national survey examining ACP in
      palliative care services demonstrates there is a need to improve systems to
      support ACP and to understand circumstances in which ACP wishes are not followed.

PMID- 25607323
TI  - Potential-controlled current responses from staircase to blip in single Pt
      nanoparticle collisions on a Ni ultramicroelectrode.
AB  - Collisions of electrocatalytic platinum (Pt) single nanoparticles (NPs) with a
      less electrocatalytic nickel (Ni) ultramicroelectrode (UME) surface were detected
      by amplification of the current by electrocatalysis of NPs. Two typical types of
      current responses, a current staircase or blip (or spike), in single NP collision
      experiments were observed at a time with a new system consisting of Pt NP/Ni
      UME/hydrazine oxidation. The staircase current response was obtained when the
      collided NPs were attached to the electrode and continued to produce
      electrocatalytic current. On the other hand, the blip current response was
      believed to be obtained when the NP attached but was deactivated. The different
      current responses depend on the different electrocatalytic reaction mechanism,
      characteristics of the NP, or the electrode material. How the deactivation of the
      electrocatalytic process affects on the current response of NP collision was
      investigated using the Ni UME. The current response of a single Pt NP collision
      is controllable from staircase to blip by changing the applied potential. The
      current response of the Pt NP was observed as a staircase response with 0 V (vs
      Ag/AgCl) and as a blip response with 0.1 V (vs Ag/AgCl) applied to the Ni UME. 

PMID- 25607324
TI  - Solitary, well-circumscribed depressed palmar lesion: challenge.

PMID- 25607325
TI  - Solitary, well-circumscribed, depressed palmar lesion.

PMID- 25607326
TI  - Choriocarcinoma-like squamous cell carcinoma: a new variant expressing human
      chorionic gonadotropin.
AB  - Cutaneous squamous cell carcinoma (SCC) has been classified into a large number
      of subtypes, which have been grouped according to malignant potential. We
      describe a new morphological variant containing areas of intermingled
      cytotrophoblast-like and syncytiotrophoblast-like cells and designate it
      "choriocarcinoma-like SCC." Furthermore, the neoplasm exhibits expression of
      human chorionic gonadotropin predominantly in the syncytiotrophoblast-like foci,
      mimicking the germ cell tumor. Human chorionic gonadotropin expression has been
      described in SCC from other organs, but not by cutaneous SCC, to our knowledge.
      This new variant could be misinterpreted as metastatic choriocarcinoma,
      especially in small punch biopsies. The frequency of this neoplasm and its
      malignant potential are undetermined.

PMID- 25607327
TI  - Multifocal epithelial sheath neuroma.

PMID- 25607328
TI  - Purpuric bullous pemphigoid.
AB  - Rare clinical variants of bullous pemphigoid (BP) include vesicular BP,
      dyshidrosiform BP, pemphigoid nodularis, seborrheic BP, pemphigoid vegetans,
      localized BP, erythrodermic BP, and juvenile BP. To our knowledge, this is the
      first report of an unusual case of purpuric BP. We present a case of 85-year-old
      white man who presented with a 2-week history of blisters and pruritic urticarial
      lesions all over his body. The diagnosis of purpuric BP was made on the basis of
      history, clinical presentation, histopathology report, direct and indirect
      immunofluorescence studies the diagnosis of purpuric BP was made. The reason for
      the development of palmoplantar purpuric lesions concomitant to ordinary patches
      and plaques of BP is unknown.

PMID- 25607329
TI  - Cytomegalovirus meningoencephalitis after rituximab treatment for primary central
      nervous system lymphoma.
AB  - The efficacy and safety of rituximab against B-cell lymphomas is well
      established. However, there has been an increased incidence of infectious
      complications after rituximab treatment, mostly hepatitis B reactivation and
      progressive multifocal leukoencephalopathy. This is the case of a 67-year-old
      patient with primary central nervous system lymphoma, who developed
      cytomegalovirus meningoencephalitis after receiving high-dose chemotherapy and
      rituximab. As there was no evidence of lymphoma relapse or additional
      immunosuppression, besides his previous treatment, an association between
      rituximab and cytomegalovirus meningoencephalitis cannot be ruled out. 

PMID- 25607330
TI  - Trigeminal herpes zoster complicated by Ramsay Hunt syndrome.
AB  - We report the case of a 55-year-old woman with herpes zoster of the mandibular
      branch of the left trigeminal nerve, which was complicated within 4 days by
      ipsilateral Ramsay Hunt syndrome. Recently, a case of trigeminal herpes zoster
      and Ramsay Hunt syndrome was described, in which the MRI and CSF findings along
      with the clinical course urged the authors to suggest the possibility of
      transaxonal spread of the virus. In our case, the findings and particularly the
      temporal relation between the 2 conditions render more plausible other
      pathophysiological mechanisms, such as the spread of the virus through the CSF. 

PMID- 25607331
TI  - MRI findings in cryptococcal meningitis of the non-HIV population.
AB  - OBJECTIVES: Cryptococcal meningitis is an opportunistic infection which can
      afflict immunocompetent and immunocompromised individuals. Imaging findings in
      the HIV population are well described; however, few studies have focused on the
      non-HIV population.The purpose of this study is to characterize clinical and
      magnetic resonance imaging (MRI) findings in the non-HIV population. METHODS: We
      performed a retrospective chart review of patients with positive CSF cryptococcal
      antigen (between 1997 and 2009) who were not HIV positive. Only patients with
      MRIs of the brain were included. Data collected included CSF findings, blood and
      CSF cryptococcal titers, and information regarding the use of immunosuppressant
      drugs. RESULTS: Nineteen patients fulfilled study criteria, and 74% of the
      patients had abnormal imaging.Ten patients were on immunosuppressants due to
      cancer, organ transplantation, or presumed vasculitis. Four patients had no known
      risk factors and 2 patients had idiopathic low CD4 counts.MRI findings in
      cryptococcal meningitis included leptomeningeal enhancement with or without a
      micronodular pattern, microcystic prominence involving the temporal lobes or
      basal ganglia, ventriculomegaly, and a brain abscess. Two patients had posterior
      fossa cysts at the foramen of Luschka. Five patients had a normal MRI.
      CONCLUSIONS: MRI findings in cryptococcal meningitis of the non-HIV population
      were more common in our series than previously recognized. In this patient
      population, leptomeningeal enhancement and intraventricular cystic lesions were
      more common than intraparenchymal findings.

PMID- 25607332
TI  - Combination treatment of interferon beta-1b and warfarin for a patient with
      Balo's concentric sclerosis and antiphospholipid syndrome.
AB  - BACKGROUND: Balo's concentric sclerosis (BCS), a rare variant of multiple
      sclerosis (MS), as the initial presentation of antiphospholipid syndrome (APS) is
      unusual. The pathogenic role of antiphospholipid antibodies in the development of
      MS remains unknown. Anticoagulant therapy might be used in patients with MS and
      APS for prevention against the relapse of MS. CASE REPORT: We present a 27-year
      old man diagnosed as BCS with APS. Initially, after corticosteroid therapy, he
      exhibited a complete recovery. During follow-up, his Balo-like lesion dissolved
      over time but transformed into other asymptomatic MS-like lesions. He also had
      persistently elevated anticardiolipin IgG levels. The patient was, therefore, on
      a combined therapy of interferon beta-1b and an anticoagulant agent. No new brain
      lesions were found on 2 occasional head magnetic resonance imaging studies at 1
      year follow-up. CONCLUSIONS: To prevent further MS relapse and thrombotic
      complications of APS, a combined therapy of interferon beta-1b and an
      anticoagulant agent can be an important strategy in treating patients with both
      BCS and APS.

PMID- 25607334
TI  - Hyperthyroidism and thrombophilia in cerebral arterial and venous thrombosis: a
      case report and critical review.
AB  - INTRODUCTION: People with hyperthyroidism, thrombophilia, or oral contraceptive
      (OC) use are reported to have a risk in developing arterial or venous thrombosis.
      There has been a rare case reporting concurrent arterial and venous thrombosis in
      such patients. CASE REPORT: We presented a 44-year-old woman with Grave disease
      and metabolic syndrome developing cerebral venous and arterial thrombosis and
      later deep vein thrombosis after OC use. At the acute stage, hyperthyroidism was
      associated with an increase in factor VIII and antithrombin III deficiency. At
      follow-up, antithrombin III level remained decreased. Her daughter with Hashimoto
      thyroiditis in a euthyroid state presenting with headache and OC use was also
      found to have antithrombin III deficiency. CONCLUSIONS: Elevated factor VIII and
      antithrombin III deficiency were associated with a series of arterial and venous
      thrombotic events in this patient. Thyroid disease and OC use may have an impact
      on these coagulation parameters. We suggested that the exclusion of thrombophilia
      and of alterations of coagulative parameters should precede any decision of OC
      prescription in thyroid disease patient with a family history of venous
      thromboembolism.

PMID- 25607333
TI  - The syndrome of stroke-like migraine attacks after radiation therapy associated
      with prolonged unresponsiveness in an adult patient.
AB  - INTRODUCTION: The syndrome of stroke-like migraine attacks after radiation
      therapy (SMART) is an extremely rare complication of cerebral irradiation. It is
      characterized by reversible episodic neurological dysfunction, commonly
      associated with headaches and occasionally with seizures, occurring years after
      cranial radiotherapy. Approximately a dozen cases have been reported in adult
      patients to date. CASE REPORT: In 1997, a 48-year-old man underwent resection of
      a right cerebellar metastasis from renal cell carcinoma, followed by whole-brain
      irradiation. Two years later he began experiencing recurrent episodes of headache
      associated with reversible left hemiparesis, dysphasia, visual field defects, and
      confusion. Over subsequent years these episodes increased in frequency, and in
      2009 and 2010 the patient experienced 2 episodes associated with seizures and
      characterized by severe depression in level of consciousness (GCS 5); the latter
      of these was particularly prolonged, with neurological recovery requiring almost
      6 months. Cortical and leptomeningeal gadolinium enhancement was demonstrated on
      magnetic resonance imaging during the second episode. Repeated
      electroencephalography studies did not demonstrate any epileptiform activity, and
      extensive workup including brain biopsy failed to identify any neoplastic,
      vascular, or infective pathology. The diagnosis of SMART syndrome was therefore
      made. CONCLUSIONS: Reduced level of consciousness of such severity and duration
      as observed here has not previously been described in SMART syndrome. This
      report, however, suggests that an excellent prognosis can be expected even in
      cases of prolonged unresponsiveness. The pathogenic mechanisms of SMART syndrome
      remain unclear, but may involve pathways common to both migraine and epilepsy.

PMID- 25607335
TI  - Orofacial pain after invasive dental procedures: neuropathic pain in perspective.
AB  - BACKGROUND: The neurologist is very familiar with the painful neuropathies of the
      trunk and extremities but, generally, to a lesser extent with those of the head
      and face. Of the latter, the neurologist is particularly familiar with ophthalmic
      zoster and trigeminal neuralgia. REVIEW SUMMARY: This review deals with
      neuropathic orofacial pain: (1) to highlight its presentation; and (2) to
      contrast it with that of neuropathic pain elsewhere in the body, including the
      head, from which it seems to differ significantly. The reason for the difference
      is also discussed as well as its implications for the diagnosis of orofacial pain
      as neuropathic. In the cases of neuropathic orofacial pain presented, the pain
      followed invasive dental procedures, making it relatively homogenous in terms of
      its etiology. The cases are contrasted with those of cranial nonorofacial and of
      noncranial painful neuropathy. CONCLUSIONS: It is suggested that the presence of
      abnormal sensory responses to touch, in the sense of paresthesia, dysesthesia, or
      allodynia, is a prerequisite for the diagnosis of neuropathic pain, when other,
      motor or sensory, signs of nerve injury ordinarily guiding the diagnosis are
      lacking, as is often the case in the face.

PMID- 25607336
TI  - Amantadine for patients with severe traumatic brain injury: a critically
      appraised topic.
AB  - BACKGROUND: Research into traumatic brain injury (TBI) has increased
      significantly. Diagnostic testing and therapeutics for patients with severe TBI
      are 2 areas on which there is increasing focus. Amantadine hydrochloride is one
      treatment considered to have potential therapeutic value in this patient
      population. OBJECTIVE: The objective was addressed through the development of a
      structured critically appraised topic. This included a clinical scenario,
      structured question, literature search strategy, critical appraisal, results,
      evidence summary, commentary, and bottom-line conclusions. Participants included
      consultant and resident neurologists, a medical librarian, clinical
      epidemiologists, and content experts in the disciplines of neurocritical care and
      physical medicine and rehabilitation. RESULTS: A multicenter, placebo-controlled,
      double-blind, randomized controlled trial was selected for review. The trial
      compared the rate of recovery, as determined by the overall Disability Rating
      Scale score, in a total of 184 patients with severe TBI. Patients were randomized
      to either receive amantadine (87) or visually identical placebo (97) over the 4
      week study interval. The rate of recovery, as measured by the Disability Rating
      Scale, was found to be greater in the treatment arm as compared with the placebo
      arm (difference in slope -0.24 points/wk, P=0.007) over the 4-week treatment
      interval. CONCLUSIONS: The results from this study demonstrated that amantadine
      hydrochloride accelerates recovery in patients with severe TBI.

PMID- 25607337
TI  - Frequency of dermatological side effects of continuous subcutaneous insulin
      infusion in children and adolescents with type 1 diabetes.
AB  - BACKGROUND: The incidence of type 1 diabetes is rising, particularly in young
      infants. The treatment with continuous subcutaneous insulin infusion (CSII)
      offers certain benefits and has gained popularity. Insulin-pump therapy could be
      associated with cutaneous-adverse effects. The purpose of our study was to
      investigate the frequency and characterization of skin-related complications in
      patients with CSII. METHODS: In a single center setting, 54 patients (28 male, 26
      female) on CSII therapy aged between 3 and 20 years participated in our study.
      Data including duration of diabetes, duration of CSII, pump model, catheter
      material, frequency of catheter switch and hygiene procedures at time of puncture
      were collected through a standardized questionnaire and photographs of affected
      areas of the skin were made. Statistical analysis was done to verify an
      association with gender, patients' age, HbA1c values, and body mass index.
      RESULTS: Our observation revealed skin complications at the site of catheter
      insertion in 43% (8 f, 15 m) of our patients. A frequent occurrence of scars
      (24%, 6 f, 7 m), lipohypertrophic areas (20%, 4 f, 7 m) and eczema (11%, 1 f, 5
      m) was observed. Furthermore, 6% (1 f, 2 m) showed changes in pigmentation and 6%
      (1 f, 2 m) lipoatrophy. The catheter localization had to be switched due to skin
      complications in 24% (6 f, 7 m) whereas none of our patients discontinued insulin
      pump therapy. CONCLUSION: Skin-related complications during CSII are frequent and
      regular examination of the insertion sites is crucial. To verify the occurrence
      of lipoatrophy associated with insulin pump therapy - an otherwise rare
      complication - larger studies would be needed.

PMID- 25607338
TI  - The comparative effect of pioglitazone and metformin on serum osteoprotegerin,
      adiponectin and intercellular adhesion molecule concentrations in patients with
      newly diagnosed type 2 diabetes: a randomized clinical trial.
AB  - AIM: The etiologic role of inflammatory pathways in the development of diabetic
      complications, especially cardiovascular events, has been established. The anti
      inflammatory role of metformin and pioglitazone has been described; however, no
      study to date has compared the efficacy of these common oral agents in this
      regard. In this study, the authors aimed to compare the anti-inflammatory
      properties of pioglitazone and metformin, with respect to their effect on serum
      concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin
      (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin. METHODS: In an
      open-label randomized clinical trial, 117 patients with newly diagnosed type 2
      diabetes mellitus were visited; 84 fulfilled the inclusion criteria, and were
      randomly allocated to 2 arms receiving either 1,000 mg/d metformin or 30 mg/d
      pioglitazone, respectively. Biochemical assessments were made at baseline and the
      end of the 3 months trial. RESULTS: Significant reduction in FPG, insulin and
      HbA1c in women and men of both arms were observed. Log-hsCRP values significantly
      decreased in both arms. A decreasing, but non-significant trend in log-OPG levels
      was observed in women of the metformin arm (p=0.063). A greater reduction in log
      ICAM levels was identifiable in men receiving pioglitazone compared to the other
      arm (p=0.008); in addition, the same trend was observed in log-OPG values
      (p=0.029). Nonetheless, reduction in log-ICAM and log-OPG levels was comparable
      between the 2 arms. A significant increase in adiponectin was observed in both
      men and women in the pioglitazone arm (p<0.001), whereas changes were non
      significant in the metformin arm. CONCLUSION: Remarkably, patients receiving
      pioglitazone revealed more significant reduction in inflammatory markers.

PMID- 25607339
TI  - Secondary IGF-I deficiency as a prognostic factor of growth hormone (GH) therapy
      effectiveness in children with isolated, non-acquired GH deficiency.
AB  - OBJECTIVE: Growth hormone (GH) deficiency (GHD) has recently been classified as
      secondary IGF-I deficiency but the significance of IGF-I measurement in
      diagnosing GHD is still discussed. The aim of the study was to assess the
      relationships between IGF-I secretion and GH therapy effectiveness in children
      with GHD. PATIENTS AND METHODS: The analysis comprised 300 children with
      isolated, non-acquired GHD (GH peak below 10 MUg/l) who completed GH therapy and
      attained final height (FH). In all patients IGF-I concentration was measured
      before the treatment and IGF-I deficiency was diagnosed if IGF-I SDS for age and
      sex was below -1.0. The following auxological indices were assessed: patients'
      height SDS before treatment (H0SDS), FH SDS and improvement of FHSDS vs. H0SDS
      (DeltaHSDS). RESULTS: In the patients with IGF-I deficiency when compared with
      those with normal IGF-I secretion before treatment, significantly better FH SDS (
      1.42+/-0.90 vs. -1.74+/-0.86, p=0.004) and DeltaHSDS (1.64+/-1.01 vs. 1.32+/
      1.05, p=0.010) were observed, despite similar H0SDS (- 3.07+/-0.78 vs. - 3.11+/
      0.77, p=0.63) and GH peak (7.0+/-3.1 MUg/l vs. 6.8+/-2.1 MUg/l, p=0.55). The
      patients who achieved FH over 10(th) centile had significantly lower IGF-I SDS
      before treatment than those with FH below 10(th) centile (- 1.59+/-1.54 vs. -
      1.20+/-1.64, p=0.04), despite similar GH peak (7.0+/-2.3 MUg/l vs. 6.7+/-3.1
      MUg/l, p=0.45). The patients with DeltaHSDS over the median value had
      significantly lower IGF-I SDS than those with DeltaHSDS below the median value (-
      1.59+/-1.71 vs. - 1.09+/-1.47, p<0.0001), despite similar GH peak (6.8+/-2.5
      MUg/l vs. 7.0+/-2.7 MUg/l, p=0.86). CONCLUSION: In children with isolated, non
      acquired GHD, secondary IGF-I deficiency is an important predictor of better GH
      therapy effectiveness.

PMID- 25607340
TI  - Clinical characteristics and predictive factors of subclinical diabetic
      nephropathy.
AB  - BACKGROUND: To investigate the clinical characteristics and predictive factors of
      subclinical diabetic nephropathy in type 2 diabetes patients. METHODS: A total of
      298 type 2 diabetes patients were divided into 3 groups based on 24-h urinary
      microalbumin and estimated glomerular filtration rate: patients with normal
      albuminuria and glomerular filtration rate (NC), patients with normoalbuminuria
      and glomerular hyperfiltration (SDN) and patients with microalbuminuria (EDN).
      The renal size, tubular injury markers and ambulatory blood pressure were
      analyzed. RESULTS: Renal size increased in the SDN and EDN groups compared to the
      NC group (P<0.05), while renal length in the SDN group was greater than the EDN
      group (P<0.05). Patients in the SDN and EDN groups had higher level of urine
      retinol binding protein and N-acetyl-beta-D-glucosaminidase and most of them
      developed proximal tubular dysfunction. The SDN group had higher 24-h mean and
      nocturnal diastolic blood pressure than the NC group (P<0.05), while the EDN
      group had higher systolic blood pressure and pulse pressure than the SDN group
      (P<0.01). More patients developed abnormal blood pressure rhythm in the SDN and
      EDN groups. The likelihood of a decrease in nocturnal systolic blood pressure was
      lower as the microalbuminuria increased. Increased renal size, more abnormal
      tubular injury markers and higher 24-h mean and nocturnal blood pressure were all
      risk factors of subclinical diabetic nephropathy. CONCLUSION: Patients with
      subclinical diabetic nephropathy had increased renal size, abnormal tubular
      injury markers, high blood pressure and abnormal circadian rhythm.

PMID- 25607341
TI  - Catalytic chalcogenylation under greener conditions: a solvent-free sulfur- and
      seleno-functionalization of olefins via I2/DMSO oxidant system.
AB  - Herein, we report a solvent- and metal-free methodology for the alkoxy
      chalcogenylation of styrenes, using molecular iodine as a catalyst, DMSO as a
      stoichiometric oxidant, and different nucleophiles under microwave irradiation.
      This eco-friendly approach afforded the desired products in good to excellent
      yields in only 10 min. In addition, using the same protocol, we carried out the
      cyclization reaction of relevant molecules, such as lapachol derivatives. 

PMID- 25607342
TI  - Colloidal aggregate and gel incubated by amorphous conjugated polymer in hybrid
      solvent medium.
AB  - A practical valuable amorphous conjugated polymer, poly(2-methoxy-5-(2'
      ethylhexyloxy)-1,4-phenylenevinylene (MEH-PPV), has been revealed to foster an
      abundance of micrometer-sized colloidal aggregates at relatively low
      concentration (below 1 wt %) in a hybrid-solvent medium that contains a
      nonsolvent, and the solution turned into gel by colloidal bridging after one-day
      aging at 30  degrees C. In contrast with typical polymer gels fostered by
      (anisotropic) chain cross-linking or planar packing on selective interacting
      sites, the MEH-PPV gel has been revealed (via dynamic light scattering, small
      angle light scattering, time-sweep dynamic modulus and optical microscope) to
      first develop featureless aggregate clusters in solution and, as the solvent
      quality worsens with reduced system temperature, bridge themselves to form gel
      through a one-dimensional (1-D) to three-dimensional (3-D) kinetic pathway.
      Combined dynamic/static light scattering analyses, along with supporting scanning
      electron microscope image and molecular dynamics simulation, indicated a
      concomitant structural reorganization within the colloidal aggregates, where
      spontaneous chain packing was perceived to form local fiber-like materials that
      are elastic by nature (i.e., a q-independent decay rate). The near coincidence of
      the above-mentioned microscopic and macroscopic phase alterations led us to
      contend that similar fibrous materials have served as the exterior bridging agent
      to fabricate colloidal strands upon gelation. The present findings clarify
      previously enigmatic, much speculative, gelation phenomena of MEH-PPV, and shed
      light on the prospect of capitalizing on specific polymer-solvent interactions to
      incubate desirable colloidal aggregates and gels in room-temperature processing
      of practical valuable conjugated polymers. 

PMID- 25607343
TI  - Quantum thermopower of metallic atomic-size contacts at room temperature.
AB  - We report conductance and thermopower measurements of metallic atomic-size
      contacts, namely gold and platinum, using a scanning tunneling microscope (STM)
      at room temperature. We find that few-atom gold contacts have an average negative
      thermopower, whereas platinum contacts present a positive thermopower, showing
      that for both metals, the sign of the thermopower in the nanoscale differs from
      that of bulk wires. We also find that the magnitude of the thermopower exhibits
      minima at the maxima of the conductance histogram in the case of gold
      nanocontacts while for platinum it presents large fluctuations. Tight-binding
      calculations and Green's function techniques, together with molecular dynamics
      simulations, show that these observations can be understood in the context of the
      Landauer-Buttiker picture of coherent transport in atomic-scale wires. In
      particular, we show that the differences in the thermopower between these two
      metals are due to the fact that the elastic transport is dominated by the 6s
      orbitals in the case of gold and by the 5d orbitals in the case of platinum. 

PMID- 25607344
TI  - Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats: Roles
      of oxidative stress, proinflammatory cytokines, and DNA damage.
AB  - Acrylamide is a hazardous substance inducing oxidative stress. Based on some
      evidence on the antioxidant properties of fenugreek, Trigonella foenum-graecum,
      this study was conducted to investigate the protective effect of fenugreek seed
      oil against acrylamide toxicity. Thirty-two male Wistar rats were randomly
      assigned into four groups. The control group was given normal saline. The second
      group was administered acrylamide (20 mg/kg bw orally). The third and fourth
      groups were administered acrylamide (20 mg/kg bw) and supplemented with 2.5% and
      5% fenugreek seed oil in their diets, respectively. Acrylamide intoxication
      significantly increased serum levels of LDH, AST, ALT, APL, gamma-GT,
      cholesterol, uric acid, urea, creatinine, 8-oxo-2'-deoxyguanosine, interleukin 1
      beta, interleukin 6, and tumor necrosis factor alpha. Moreover, it increased
      hepatic, renal, and brain lipid peroxidation, while it impaired the activities
      and concentrations of the antioxidant biomarkers. Fenugreek oil supplementation
      normalized the altered serum parameters, prevented lipid peroxidation, and
      enhanced the antioxidant biomarker concentrations and activities in the hepatic,
      renal, and brain tissues of acrylamide-intoxicated rats in a dose-dependent
      manner. Thus, these results indicate that Trigonella foenum-graecum oil has a
      protective effect against acrylamide-induced toxicity through its free radical
      scavenging and potent antioxidant activities. 

PMID- 25607345
TI  - Upward electrical discharges observed above Tropical Depression Dorian.
AB  - Observation of upward electrical discharges from thunderstorms has been
      sporadically reported in the scientific literature. According to their terminal
      altitudes, they are classified as starters (20-30 km), jets (40-50 km) and
      gigantic jets (70-90 km). They not only have a significant impact on the occupied
      atmospheric volumes but also electrically couple different atmospheric regions.
      However, as they are rare and unpredictable, our knowledge of them has been built
      on observations that typically record only one type of such discharges. Here we
      report a close-distance observation of seven upward discharges including one
      starter, two jets and four gigantic jets above Tropical Depression Dorian. Our
      optical and electromagnetic data indicate that all events are of negative
      polarity, suggesting they are initiated in the same thundercloud charge region.
      The data also indicate that the lightning-like discharge channel can extend above
      thunderclouds by about 30 km, but the discharge does not emit low-frequency
      electromagnetic radiation as normal lightning.

PMID- 25607346
TI  - beta-NaGdF4 nanotubes: one-pot synthesis and luminescence properties.
AB  - Hexagonal-phase NaGdF4 nanotubes were successfully fabricated through a template-
      and catalyst-free method in a hydrothermal environment. The intrinsic and
      external factors contributing to the formation of tubular nanocrystals were
      discussed, namely the anisotropic crystal structure of the hexagonal-phase NaGdF4
      and the insufficient supply of reagents. Furthermore, the addition of ethylene
      glycol and hydrazine had a significant effect on the morphological variation. The
      desirable multicolor outputs were achieved by co-doping Ce(3+) and Ln(3+) (Ln =
      Eu, Tb, and Dy) ions in the NaGdF4 crystal, in which the Gd(3+) ions acted as an
      intermediate medium transforming the excitation energy to the activator ions.
      Finally, the upconversion luminescence and magnetic performance of the sodium
      rare earth fluoride were demonstrated. 

PMID- 25607348
TI  - The accessible cellulose surface influences cellulase synergism during the
      hydrolysis of lignocellulosic substrates.
AB  - Effective enzymatic hydrolysis of insoluble cellulose requires the synergistic
      action of a suite of cellulase components. Most previous studies have only
      assessed cellulase synergism on model cellulosic substrates. When the actions of
      individual and combinations of cellulases (Cel7A, Cel6A, Cel7B, Cel5A) were
      assessed on various pretreated lignocellulosic substrates, Cel7A was shown to be
      the major contributor to overall cellulose hydrolysis, with the other enzymes
      synergistically enhancing its hydrolytic efficiency, at least partially, by
      facilitating Cel7A desorption (assessed by a double-sandwich enzyme-linked
      immunosorbent assay). When the influences of various substrate physicochemical
      characteristics on the effectiveness of enzyme synergism were assessed, a strong
      relationship was observed between cellulose accessibility (as determined by the
      cellulose binding module technique) and the degree of synergism, with greater
      synergy observed on the more disorganized/accessible cellulose surface. 

PMID- 25607347
TI  - The effects of bisphosphonates on ectopic soft tissue mineralization caused by
      mutations in the ABCC6 gene.
AB  - Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy
      (GACI) are heritable ectopic mineralization disorders. Most cases of PXE and many
      cases of GACI harbor mutations in the ABCC6 gene. There is no effective treatment
      for these disorders. We explored the potential efficacy of bisphosphonates to
      prevent ectopic calcification caused by ABCC6 mutations by feeding Abcc6(-/-)
      mice with diet containing etidronate disodium (ETD) or alendronate sodium
      trihydrate (AST) in quantities corresponding to 1x, 5x, or 12x of the doses used
      to treat osteoporosis in humans. The mice were placed on diet at 4 weeks of age,
      and the degree of mineralization was assessed at 12 weeks by quantitation of the
      calcium deposits in the dermal sheath of vibrissae, a progressive biomarker of
      the mineralization, by computerized morphometry of histopathologic sections and
      by direct chemical assay of calcium. We found that ETD, but not AST, at the 12x
      dosage, significantly reduced mineralization, suggesting that selected
      bisphosphonates may be helpful for prevention of mineral deposits in PXE and GACI
      caused by mutations in the ABCC6 gene, when combined with careful monitoring of
      efficacy and potential side-effects. 

PMID- 25607349
TI  - Capacitive deionization on-chip as a method for microfluidic sample preparation.
AB  - Desalination as a sample preparation step is essential for noise reduction and
      reproducibility of mass spectrometry measurements. A specific example is the
      analysis of proteins for medical research and clinical applications. Salts and
      buffers that are present in samples need to be removed before analysis to improve
      the signal-to-noise ratio. Capacitive deionization is an electrostatic
      desalination (CDI) technique which uses two porous electrodes facing each other
      to remove ions from a solution. Upon the application of a potential of 0.5 V ions
      migrate to the electrodes and are stored in the electrical double layer. In this
      article we demonstrate CDI on a chip, and desalinate a solution by the removal of
      23% of Na(+) and Cl(-) ions, while the concentration of a larger molecule (FITC
      dextran) remains unchanged. For the first time impedance spectroscopy is
      introduced to monitor the salt concentration in situ in real-time in between the
      two desalination electrodes. 

PMID- 25607350
TI  - Post-transcriptional modifications are very important after all.

PMID- 25607351
TI  - Downregulation of peroxiredoxin-1 by beta-elemene enhances the radiosensitivity
      of lung adenocarcinoma xenografts.
AB  - beta-elemene, the active component of elemene (1-methyl-1-vinyl-2,4-diisopropenyl
      cyclohexane), is a naturally occurring compound isolated from the traditional
      Chinese medicinal herb Curcuma wenyujin. Studies have confirmed that beta-elemene
      enhances the radiosensitivity of lung cancer cell lines such as A549, by multiple
      pathways; however, their underlying mechanisms and pathways are yet to be
      elucidated. In the present study, two-dimensional differential in-gel
      electrophoresis and matrix-assisted laser desorption/ionization time-of-flight
      tandem mass spectrometry were used to profile the different proteins in A549 cell
      xenograft models of both treatment groups. The protein/mRNA expression was
      assessed by reverse transcription-polymerase chain reaction and western blotting
      techniques in tumor samples from all treatment groups. As a critical player in
      redox regulation of cancer cells, inhibition of peroxiredoxin-1 (Prx-1) may be an
      effective option for enhancing the tumor response to radiation. We further
      verified Prx-1 expression at the transcription and translation levels. beta
      elemene at a dose of 45 mg/kg had little effect on the Prx-1 protein expression,
      which was correlated with a moderate antitumor effect. However, a 45 mg/kg dose
      of beta-elemene significantly inhibited the Prx-1 mRNA expression, thereby
      suggesting a possible influence on the transcriptional process, and radiation
      significantly increased the Prx-1 mRNA/protein expression compared to the control
      group (p<0.01). Notably, Prx-1 mRNA/protein expression was significantly lower in
      the beta-elemene/radiation co-treatment group compared to the baseline levels in
      the control group (p<0.01). These results suggest that radiation-induced Prx-1
      expression is directly or indirectly suppressed by beta-elemene, thus suggesting
      a new pathway by which to reverse radioresistance.

PMID- 25607352
TI  - New energetic polynitrotetrazoles.
AB  - This combined experimental, theoretical and comparative study details the
      syntheses and chemical characterisation of two new energetic polynitromethyl
      tetrazole derivatives, namely, 2-(2-nitro-2-azapropyl)-5-(trinitromethyl)-2 H
      tetrazole and its fluorine-containing analogue 2-(2-nitro-2-azapropyl)-5
      (fluorodinitromethyl)-2 H-tetrazole. Their crystal structures and energetic
      behaviour are compared to those of their starting materials, the ammonium salts
      of the corresponding 5-(polynitromethyl)-2 H-tetrazoles. Additionally, the
      crystal structures of two further related polynitrotetrazoles are presented. 

PMID- 25607353
TI  - Corrigendum: The adipokine Retnla modulates cholesterol homeostasis in
      hyperlipidemic mice.

PMID- 25607354
TI  - Selecting core-hole localization or delocalization in CS2 by photofragmentation
      dynamics.
AB  - Electronic core levels in molecules are highly localized around one atomic site.
      However, in single-photon ionization of symmetric molecules, the question of core
      hole localization versus delocalization over two equivalent atoms has long been
      debated as the answer lies at the heart of quantum mechanics. Here, using a joint
      experimental and theoretical study of core-ionized carbon disulfide (CS2), we
      demonstrate that it is possible to experimentally select distinct molecular
      fragmentation pathways in which the core hole can be considered as either
      localized on one sulfur atom or delocalized between two indistinguishable sulfur
      atoms. This feat is accomplished by measuring photoelectron angular distributions
      within the frame of the molecule, directly probing entanglement or
      disentanglement of quantum pathways as a function of how the molecule
      dissociates. 

PMID- 25607355
TI  - Recharge of a subglacial lake by surface meltwater in northeast Greenland.
AB  - In a warming climate, surface meltwater production on large ice sheets is
      expected to increase. If this water is delivered to the ice sheet base it may
      have important consequences for ice dynamics. For example, basal water
      distributed in a diffuse network can decrease basal friction and accelerate ice
      flow, whereas channelized basal water can move quickly to the ice margin, where
      it can alter fjord circulation and submarine melt rates. Less certain is whether
      surface meltwater can be trapped and stored in subglacial lakes beneath large ice
      sheets. Here we show that a subglacial lake in Greenland drained quickly, as seen
      in the collapse of the ice surface, and then refilled from surface meltwater
      input. We use digital elevation models from stereo satellite imagery and airborne
      measurements to resolve elevation changes during the evolution of the surface and
      basal hydrologic systems at the Flade Isblink ice cap in northeast Greenland.
      During the autumn of 2011, a collapse basin about 70 metres deep and about 0.4
      cubic kilometres in volume formed near the southern summit of the ice cap as a
      subglacial lake drained into a nearby fjord. Over the next two years, rapid
      uplift of the floor of the basin (which is approximately 8.4 square kilometres in
      area) occurred as surface meltwater flowed into crevasses around the basin margin
      and refilled the subglacial lake. Our observations show that surface meltwater
      can be trapped and stored at the bed of an ice sheet. Sensible and latent heat
      released by this trapped meltwater could soften nearby colder basal ice and alter
      downstream ice dynamics. Heat transport associated with meltwater trapped in
      subglacial lakes should be considered when predicting how ice sheet behaviour
      will change in a warming climate. 

PMID- 25607356
TI  - Recoded organisms engineered to depend on synthetic amino acids.
AB  - Genetically modified organisms (GMOs) are increasingly used in research and
      industrial systems to produce high-value pharmaceuticals, fuels and chemicals.
      Genetic isolation and intrinsic biocontainment would provide essential biosafety
      measures to secure these closed systems and enable safe applications of GMOs in
      open systems, which include bioremediation and probiotics. Although safeguards
      have been designed to control cell growth by essential gene regulation, inducible
      toxin switches and engineered auxotrophies, these approaches are compromised by
      cross-feeding of essential metabolites, leaked expression of essential genes, or
      genetic mutations. Here we describe the construction of a series of genomically
      recoded organisms (GROs) whose growth is restricted by the expression of multiple
      essential genes that depend on exogenously supplied synthetic amino acids (sAAs).
      We introduced a Methanocaldococcus jannaschii tRNA:aminoacyl-tRNA synthetase pair
      into the chromosome of a GRO derived from Escherichia coli that lacks all TAG
      codons and release factor 1, endowing this organism with the orthogonal
      translational components to convert TAG into a dedicated sense codon for sAAs.
      Using multiplex automated genome engineering, we introduced in-frame TAG codons
      into 22 essential genes, linking their expression to the incorporation of
      synthetic phenylalanine-derived amino acids. Of the 60 sAA-dependent variants
      isolated, a notable strain harbouring three TAG codons in conserved functional
      residues of MurG, DnaA and SerS and containing targeted tRNA deletions maintained
      robust growth and exhibited undetectable escape frequencies upon culturing
      ~10(11) cells on solid media for 7 days or in liquid media for 20 days. This is a
      significant improvement over existing biocontainment approaches. We constructed
      synthetic auxotrophs dependent on sAAs that were not rescued by cross-feeding in
      environmental growth assays. These auxotrophic GROs possess alternative genetic
      codes that impart genetic isolation by impeding horizontal gene transfer and now
      depend on the use of synthetic biochemical building blocks, advancing orthogonal
      barriers between engineered organisms and the environment. 

PMID- 25607357
TI  - Emotional learning selectively and retroactively strengthens memories for related
      events.
AB  - Neurobiological models of long-term memory propose a mechanism by which initially
      weak memories are strengthened through subsequent activation that engages common
      neural pathways minutes to hours later. This synaptic tag-and-capture model has
      been hypothesized to explain how inconsequential information is selectively
      consolidated following salient experiences. Behavioural evidence for tag-and
      capture is provided by rodent studies in which weak early memories are
      strengthened by future behavioural training. Whether a process of behavioural
      tagging occurs in humans to transform weak episodic memories into stable long
      term memories is unknown. Here we show, in humans, that information is
      selectively consolidated if conceptually related information, putatively
      represented in a common neural substrate, is made salient through an emotional
      learning experience. Memory for neutral objects was selectively enhanced if other
      objects from the same category were paired with shock. Retroactive enhancements
      as a result of emotional learning were observed following a period of
      consolidation, but were not observed in an immediate memory test or for items
      strongly encoded before fear conditioning. These findings provide new evidence
      for a generalized retroactive memory enhancement, whereby inconsequential
      information can be retroactively credited as relevant, and therefore selectively
      remembered, if conceptually related information acquires salience in the future. 

PMID- 25607359
TI  - Metabolic coupling of two small-molecule thiols programs the biosynthesis of
      lincomycin A.
AB  - Low-molecular-mass thiols in organisms are well known for their redox-relevant
      role in protection against various endogenous and exogenous stresses. In
      eukaryotes and Gram-negative bacteria, the primary thiol is glutathione (GSH), a
      cysteinyl-containing tripeptide. In contrast, mycothiol (MSH), a cysteinyl pseudo
      disaccharide, is dominant in Gram-positive actinobacteria, including antibiotic
      producing actinomycetes and pathogenic mycobacteria. MSH is equivalent to GSH,
      either as a cofactor or as a substrate, in numerous biochemical processes, most
      of which have not been characterized, largely due to the dearth of information
      concerning MSH-dependent proteins. Actinomycetes are able to produce another
      thiol, ergothioneine (EGT), a histidine betaine derivative that is widely
      assimilated by plants and animals for variable physiological activities. The
      involvement of EGT in enzymatic reactions, however, lacks any precedent. Here we
      report that the unprecedented coupling of two bacterial thiols, MSH and EGT, has
      a constructive role in the biosynthesis of lincomycin A, a sulfur-containing
      lincosamide (C8 sugar) antibiotic that has been widely used for half a century to
      treat Gram-positive bacterial infections. EGT acts as a carrier to template the
      molecular assembly, and MSH is the sulfur donor for lincomycin maturation after
      thiol exchange. These thiols function through two unusual S-glycosylations that
      program lincosamide transfer, activation and modification, providing the first
      paradigm for EGT-associated biochemical processes and for the poorly understood
      MSH-dependent biotransformations, a newly described model that is potentially
      common in the incorporation of sulfur, an element essential for life and
      ubiquitous in living systems. 

PMID- 25607361
TI  - Apico-basal forces exerted by apoptotic cells drive epithelium folding.
AB  - Epithelium folding is a basic morphogenetic event that is essential in
      transforming simple two-dimensional epithelial sheets into three-dimensional
      structures in both vertebrates and invertebrates. Folding has been shown to rely
      on apical constriction. The resulting cell-shape changes depend either on
      adherens junction basal shift or on a redistribution of myosin II, which could be
      driven by mechanical signals. Yet the initial cellular mechanisms that trigger
      and coordinate cell remodelling remain largely unknown. Here we unravel the
      active role of apoptotic cells in initiating morphogenesis, thus revealing a
      novel mechanism of epithelium folding. We show that, in a live developing tissue,
      apoptotic cells exert a transient pulling force upon the apical surface of the
      epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic
      cells then induce a non-autonomous increase in tissue tension together with
      cortical myosin II apical stabilization in the surrounding tissue, eventually
      resulting in epithelium folding. Together our results, supported by a theoretical
      biophysical three-dimensional model, identify an apoptotic myosin-II-dependent
      signal as the initial signal leading to cell reorganization and tissue folding.
      This work further reveals that, far from being passively eliminated as generally
      assumed (for example, during digit individualization), apoptotic cells actively
      influence their surroundings and trigger tissue remodelling through regulation of
      tissue tension. 

PMID- 25607363
TI  - Biochemistry: Elusive source of sulfur unravelled.

PMID- 25607364
TI  - Structure of the key species in the enzymatic oxidation of methane to methanol.
AB  - Methane monooxygenase (MMO) catalyses the O2-dependent conversion of methane to
      methanol in methanotrophic bacteria, thereby preventing the atmospheric egress of
      approximately one billion tons of this potent greenhouse gas annually. The key
      reaction cycle intermediate of the soluble form of MMO (sMMO) is termed compound
      Q (Q). Q contains a unique dinuclear Fe(IV) cluster that reacts with methane to
      break an exceptionally strong 105 kcal mol(-1) C-H bond and insert one oxygen
      atom. No other biological oxidant, except that found in the particulate form of
      MMO, is capable of such catalysis. The structure of Q remains controversial
      despite numerous spectroscopic, computational and synthetic model studies. A
      definitive structural assignment can be made from resonance Raman vibrational
      spectroscopy but, despite efforts over the past two decades, no vibrational
      spectrum of Q has yet been obtained. Here we report the core structures of Q and
      the following product complex, compound T, using time-resolved resonance Raman
      spectroscopy (TR(3)). TR(3) permits fingerprinting of intermediates by their
      unique vibrational signatures through extended signal averaging for short-lived
      species. We report unambiguous evidence that Q possesses a bis-MU-oxo diamond
      core structure and show that both bridging oxygens originate from O2. This
      observation strongly supports a homolytic mechanism for O-O bond cleavage. We
      also show that T retains a single oxygen atom from O2 as a bridging ligand, while
      the other oxygen atom is incorporated into the product. Capture of the extreme
      oxidizing potential of Q is of great contemporary interest for bioremediation and
      the development of synthetic approaches to methane-based alternative fuels and
      chemical industry feedstocks. Insight into the formation and reactivity of Q from
      the structure reported here is an important step towards harnessing this
      potential. 

PMID- 25607366
TI  - Biocontainment of genetically modified organisms by synthetic protein design.
AB  - Genetically modified organisms (GMOs) are increasingly deployed at large scales
      and in open environments. Genetic biocontainment strategies are needed to prevent
      unintended proliferation of GMOs in natural ecosystems. Existing biocontainment
      methods are insufficient because they impose evolutionary pressure on the
      organism to eject the safeguard by spontaneous mutagenesis or horizontal gene
      transfer, or because they can be circumvented by environmentally available
      compounds. Here we computationally redesign essential enzymes in the first
      organism possessing an altered genetic code (Escherichia coli strain C321.DeltaA)
      to confer metabolic dependence on non-standard amino acids for survival. The
      resulting GMOs cannot metabolically bypass their biocontainment mechanisms using
      known environmental compounds, and they exhibit unprecedented resistance to
      evolutionary escape through mutagenesis and horizontal gene transfer. This work
      provides a foundation for safer GMOs that are isolated from natural ecosystems by
      a reliance on synthetic metabolites. 

PMID- 25607367
TI  - Biochemistry: Breaking methane.

PMID- 25607368
TI  - RBM3 mediates structural plasticity and protective effects of cooling in
      neurodegeneration.
AB  - In the healthy adult brain synapses are continuously remodelled through a process
      of elimination and formation known as structural plasticity. Reduction in synapse
      number is a consistent early feature of neurodegenerative diseases, suggesting
      deficient compensatory mechanisms. Although much is known about toxic processes
      leading to synaptic dysfunction and loss in these disorders, how synaptic
      regeneration is affected is unknown. In hibernating mammals, cooling induces loss
      of synaptic contacts, which are reformed on rewarming, a form of structural
      plasticity. We have found that similar changes occur in artificially cooled
      laboratory rodents. Cooling and hibernation also induce a number of cold-shock
      proteins in the brain, including the RNA binding protein, RBM3 (ref. 6). The
      relationship of such proteins to structural plasticity is unknown. Here we show
      that synapse regeneration is impaired in mouse models of neurodegenerative
      disease, in association with the failure to induce RBM3. In both prion-infected
      and 5XFAD (Alzheimer-type) mice, the capacity to regenerate synapses after
      cooling declined in parallel with the loss of induction of RBM3. Enhanced
      expression of RBM3 in the hippocampus prevented this deficit and restored the
      capacity for synapse reassembly after cooling. RBM3 overexpression, achieved
      either by boosting endogenous levels through hypothermia before the loss of the
      RBM3 response or by lentiviral delivery, resulted in sustained synaptic
      protection in 5XFAD mice and throughout the course of prion disease, preventing
      behavioural deficits and neuronal loss and significantly prolonging survival. In
      contrast, knockdown of RBM3 exacerbated synapse loss in both models and
      accelerated disease and prevented the neuroprotective effects of cooling. Thus,
      deficient synapse regeneration, mediated at least in part by failure of the RBM3
      stress response, contributes to synapse loss throughout the course of
      neurodegenerative disease. The data support enhancing cold-shock pathways as
      potential protective therapies in neurodegenerative disorders. 

PMID- 25607369
TI  - Neurodegeneration: Cold shock protects the brain.

PMID- 25607370
TI  - Cell biology: Death drags down the neighbourhood.

PMID- 25607371
TI  - Predicting climate-driven regime shifts versus rebound potential in coral reefs.
AB  - Climate-induced coral bleaching is among the greatest current threats to coral
      reefs, causing widespread loss of live coral cover. Conditions under which reefs
      bounce back from bleaching events or shift from coral to algal dominance are
      unknown, making it difficult to predict and plan for differing reef responses
      under climate change. Here we document and predict long-term reef responses to a
      major climate-induced coral bleaching event that caused unprecedented region-wide
      mortality of Indo-Pacific corals. Following loss of >90% live coral cover, 12 of
      21 reefs recovered towards pre-disturbance live coral states, while nine reefs
      underwent regime shifts to fleshy macroalgae. Functional diversity of associated
      reef fish communities shifted substantially following bleaching, returning
      towards pre-disturbance structure on recovering reefs, while becoming
      progressively altered on regime shifting reefs. We identified threshold values
      for a range of factors that accurately predicted ecosystem response to the
      bleaching event. Recovery was favoured when reefs were structurally complex and
      in deeper water, when density of juvenile corals and herbivorous fishes was
      relatively high and when nutrient loads were low. Whether reefs were inside no
      take marine reserves had no bearing on ecosystem trajectory. Although conditions
      governing regime shift or recovery dynamics were diverse, pre-disturbance
      quantification of simple factors such as structural complexity and water depth
      accurately predicted ecosystem trajectories. These findings foreshadow the likely
      divergent but predictable outcomes for reef ecosystems in response to climate
      change, thus guiding improved management and adaptation. 

PMID- 25607372
TI  - Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic
      methylation.
AB  - DNA methylation is an epigenetic modification associated with transcriptional
      repression of promoters and is essential for mammalian development. Establishment
      of DNA methylation is mediated by the de novo DNA methyltransferases DNMT3A and
      DNMT3B, whereas DNMT1 ensures maintenance of methylation through replication.
      Absence of these enzymes is lethal, and somatic mutations in these genes have
      been associated with several human diseases. How genomic DNA methylation patterns
      are regulated remains poorly understood, as the mechanisms that guide recruitment
      and activity of DNMTs in vivo are largely unknown. To gain insights into this
      matter we determined genomic binding and site-specific activity of the mammalian
      de novo DNA methyltransferases DNMT3A and DNMT3B. We show that both enzymes
      localize to methylated, CpG-dense regions in mouse stem cells, yet are excluded
      from active promoters and enhancers. By specifically measuring sites of de novo
      methylation, we observe that enzymatic activity reflects binding. De novo
      methylation increases with CpG density, yet is excluded from nucleosomes.
      Notably, we observed selective binding of DNMT3B to the bodies of transcribed
      genes, which leads to their preferential methylation. This targeting to
      transcribed sequences requires SETD2-mediated methylation of lysine 36 on histone
      H3 and a functional PWWP domain of DNMT3B. Together these findings reveal how
      sequence and chromatin cues guide de novo methyltransferase activity to ensure
      methylome integrity. 

PMID- 25607373
TI  - Reconciling the convergence of supraspinous fossa shape among hominoids in light
      of locomotor differences.
AB  - Differences in scapular morphology between modern humans and the African and
      lesser apes are associated with the distinct locomotor habits of these groups.
      However, several traits, particularly aspects of the supraspinous fossa, are
      convergent between Homo and Pongo-an unexpected result given their divergent
      locomotor habits. Many morphological assessments of the scapula rely on the
      limited number of static landmarks available, and traditional approaches like
      these tend to oversimplify scapular shape. Here, we present the results of two
      geometric morphometric (GM) analyses of hominoid supraspinous fossa shape-one
      employing five homologous landmarks and another with 83 sliding semilandmarks
      alongside those of traditional methods to evaluate if three-dimensional
      considerations of fossa shape afford more comprehensive insights into scapular
      shape and functional morphology. Traditional measures aligned Pongo and Homo with
      narrow and transversely oriented supraspinous fossae, whereas African ape and
      Hylobates fossae are broader and more obliquely situated. However, our GM results
      highlight that much of the convergence between Homo and Pongo is reflective of
      their more medially positioned superior angles. These approaches offered a more
      complete assessment of supraspinous shape and revealed that the Homo fossa, with
      an intermediate superior angle position and moderate superoinferior expansion, is
      actually reminiscent of the African ape shape. Additionally, both Pongo and
      Hylobates were shown to have more compressed fossae, something that has not
      previously been identified through traditional analyses. Thus, the total
      morphological pattern of the Pongo supraspinous fossa is unique among hominoids,
      and possibly indicative of its distinctive locomotor habits.

PMID- 25607375
TI  - Accurate determination of the diffusion coefficient of proteins by Fourier
      analysis with whole column imaging detection.
AB  - Analysis in the frequency domain is considered a powerful tool to elicit precise
      information from spectroscopic signals. In this study, the Fourier transformation
      technique is employed to determine the diffusion coefficient (D) of a number of
      proteins in the frequency domain. Analytical approaches are investigated for
      determination of D from both experimental and data treatment viewpoints. The
      diffusion process is modeled to calculate diffusion coefficients based on the
      Fourier transformation solution to Fick's law equation, and its results are
      compared to time domain results. The simulations characterize optimum spatial and
      temporal conditions and demonstrate the noise tolerance of the method. The
      proposed model is validated by its application for the electropherograms from the
      diffusion path of a set of proteins. Real-time dynamic scanning is conducted to
      monitor dispersion by employing whole column imaging detection technology in
      combination with capillary isoelectric focusing (CIEF) and the imaging plug flow
      (iPF) experiment. These experimental techniques provide different peak shapes,
      which are utilized to demonstrate the Fourier transformation ability in
      extracting diffusion coefficients out of irregular shape signals. Experimental
      results confirmed that the Fourier transformation procedure substantially
      enhanced the accuracy of the determined values compared to those obtained in the
      time domain. 

PMID- 25607374
TI  - Rare variants in RTEL1 are associated with familial interstitial pneumonia.
AB  - RATIONALE: Up to 20% of cases of idiopathic interstitial pneumonia cluster in
      families, comprising the syndrome of familial interstitial pneumonia (FIP);
      however, the genetic basis of FIP remains uncertain in most families. OBJECTIVES:
      To determine if new disease-causing rare genetic variants could be identified
      using whole-exome sequencing of affected members from FIP families, providing
      additional insights into disease pathogenesis. METHODS: Affected subjects from 25
      kindreds were selected from an ongoing FIP registry for whole-exome sequencing
      from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing,
      and cosegregation analysis was performed in families, followed by additional
      sequencing of affected individuals from another 163 kindreds. MEASUREMENTS AND
      MAIN RESULTS: We identified a potentially damaging rare variant in the gene
      encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated
      with disease and was associated with very short telomeres in peripheral blood
      mononuclear cells in 1 of 25 families in our original whole-exome sequencing
      cohort. Evaluation of affected individuals in 163 additional kindreds revealed
      another eight families (4.7%) with heterozygous rare variants in RTEL1 that
      segregated with clinical FIP. Probands and unaffected carriers of these rare
      variants had short telomeres (<10% for age) in peripheral blood mononuclear cells
      and increased T-circle formation, suggesting impaired RTEL1 function.
      CONCLUSIONS: Rare loss-of-function variants in RTEL1 represent a newly defined
      genetic predisposition for FIP, supporting the importance of telomere-related
      pathways in pulmonary fibrosis.

PMID- 25607376
TI  - Recombinant adeno-associated virus-, polyethylenimine/plasmid- and
      lipofectamine/carboxyfluorescein-labeled small interfering RNA-based transfection
      in retinal pigment epithelial cells with ultrasound and/or SonoVue.
AB  - The present study was conducted to investigate the efficacy and safety of
      ultrasound (US)-mediated transfection of the type 2 recombinant adeno-associated
      virus (AAV) vectors encoding the enhanced green fluorescent protein (EGFP) gene
      (rAAV), polyethylenimine (PEI)/plasmid EGFP-N1 (pDNA) or lipofectamine
      (L)/carboxyfluorescein (FAM)-labeled small interfering RNA (siRNA) in the human
      ARPE-19 retinal pigment epithelial (RPE) cell line, with or without the addition
      of SonoVue. Cultured RPE cells were exposed to US, with or without SonoVue under
      different conditions, including variation in the intensity and duration of
      treatment, and the dose of microbubbles. The effects of ultrasound-targeted
      microbubble destruction (UTMD) on the structure of pDNA and the transfection
      ability of rAAV, PEI/pDNA and L/siRNA were also evaluated. Furthermore, the
      effect of UTMD on RPE cells was evaluated at 0 and 24 h following UTMD. US
      mediated transfection (USMT) significantly increased L/siRNA transfection
      efficiency, as measured by the transgene expression per cell and the percentage
      of transfected cells. UTMD significantly increased rAAV and PEI/pDNA transfer to
      RPE cells. UTMD-mediated rAAV or PEI/pDNA delivery was more effective than USMT
      mediated delivery of siRNA. Evaluating cell viability at 24 h post-UTMD provided
      more valuable information than immediate evaluation following UTMD. Furthermore,
      there was minimal cytotoxicity and minimal change to the structure of pDNA under
      the optimal parameters. UTMD/US may be of use in enhancing rAAV, PEI/pDNA and
      L/siRNA transgene expression of ARPE-19 cells in vitro. Studies on the
      transfection of different nucleotides (such as pDNA and siRNA) and different
      types of vectors (chemical and biological) mediated by UTMD may provide useful
      information to guide future in vivo and transfection studies.

PMID- 25607377
TI  - Generating free charges by carrier multiplication in quantum dots for highly
      efficient photovoltaics.
AB  - CONSPECTUS: In a conventional photovoltaic device (solar cell or photodiode)
      photons are absorbed in a bulk semiconductor layer, leading to excitation of an
      electron from a valence band to a conduction band. Directly after
      photoexcitation, the hole in the valence band and the electron in the conduction
      band have excess energy given by the difference between the photon energy and the
      semiconductor band gap. In a bulk semiconductor, the initially hot charges
      rapidly lose their excess energy as heat. This heat loss is the main reason that
      the theoretical efficiency of a conventional solar cell is limited to the
      Shockley-Queisser limit of ~33%. The efficiency of a photovoltaic device can be
      increased if the excess energy is utilized to excite additional electrons across
      the band gap. A sufficiently hot charge can produce an electron-hole pair by
      Coulomb scattering on a valence electron. This process of carrier multiplication
      (CM) leads to formation of two or more electron-hole pairs for the absorption of
      one photon. In bulk semiconductors such as silicon, the energetic threshold for
      CM is too high to be of practical use. However, CM in nanometer sized
      semiconductor quantum dots (QDs) offers prospects for exploitation in
      photovoltaics. CM leads to formation of two or more electron-hole pairs that are
      initially in close proximity. For photovoltaic applications, these charges must
      escape from recombination. This Account outlines our recent progress in the
      generation of free mobile charges that result from CM in QDs. Studies of charge
      carrier photogeneration and mobility were carried out using (ultrafast) time
      resolved laser techniques with optical or ac conductivity detection. We found
      that charges can be extracted from photoexcited PbS QDs by bringing them into
      contact with organic electron and hole accepting materials. However, charge
      localization on the QD produces a strong Coulomb attraction to its counter charge
      in the organic material. This limits the production of free charges that can
      contribute to the photocurrent in a device. We show that free mobile charges can
      be efficiently produced via CM in solids of strongly coupled PbSe QDs. Strong
      electronic coupling between the QDs resulted in a charge carrier mobility of the
      order of 1 cm(2) V(-1) s(-1). This mobility is sufficiently high so that
      virtually all electron-hole pairs escape from recombination. The impact of
      temperature on the CM efficiency in PbSe QD solids was also studied. We inferred
      that temperature has no observable effect on the rate of cooling of hot charges
      nor on the CM rate. We conclude that exploitation of CM requires that charges
      have sufficiently high mobility to escape from recombination. The contribution of
      CM to the efficiency of photovoltaic devices can be further enhanced by an
      increase of the CM efficiency above the energetic threshold of twice the band
      gap. For large-scale applications in photovoltaic devices, it is important to
      develop abundant and nontoxic materials that exhibit efficient CM.

PMID- 25607378
TI  - Trigger matters: an ergonomy analysis of insulin pens.
AB  - BACKGROUND: Excessive force required to deliver a set dose of insulin as well as
      a localization of the push button and its upwards extension may result in
      significant difficulties to safely perform insulin injection, including
      bending/breakage of the injector's needle. The GensuPen2 (Copernicus/Bioton,
      Warsaw, Poland) pen has a unique spring-assisted delivery system and a lateral
      trigger device for injection of insulin to improve its ergonomics. We tested the
      force required to administer insulin using three pens: GensuPen2, NovoPen((r)) 4
      (Novo Nordisk, Bagsvaerd, Denmark), and HumaPen Ergo((r)) (Eli Lilly,
      Indianapolis, IN). MATERIALS AND METHODS: Using a certified dynamometer we tested
      injection force at three doses of insulin: 2, 30, and 60 U, using each of the
      three injectors (n=10) in triplicate. Area under the curve (AUC) and maximum
      force used were calculated for each series of injections. RESULTS: When
      administering doses of 2, 30, and 60 units of insulin, the GensuPen2 (6.55+/
      1.09, 6.52+/-1.92, and 6.89+/-1.15 N, respectively) required significantly lower
      maximum force than the NovoPen 4 (9.04+/-0.61, 12.96+/-1.45, and 15.42+/-0.99 N,
      respectively) and the HumaPen Ergo (17.66+/-1.88, 32.14+/-6.08, and 40.39+/-7.64
      N, respectively) (all P<0.0001). The AUC of force used for insulin injection with
      GensuPen2 did not differ between doses (P=0.82). At all dose levels, GensuPen2
      required significantly lower force than the other two injectors. Moreover, the
      mode of holding of GensuPen2 was more similar to the natural arrangement of the
      hand while gripping a cylindrical item in comparison with NovoPen 4 and HumaPen
      Ergo. CONCLUSIONS: Usage of the GensuPen2 injector with a lateral trigger
      location and spring-assisted delivery system reduces the force required for drug
      administration, especially at high doses of insulin.

PMID- 25607379
TI  - The fine structure of Pearlman's catalyst.
AB  - Pearlman's catalyst, nominally Pd(OH)2/C, is widely used as for hydrogenation
      reactions and C-C coupling reactions. Contrary to the accepted view, we show that
      Pearlman's catalyst as prepared and after drying consists of carbon supported
      (mostly) nano-particulate hydrous palladium oxide capped with a monolayer of
      hydroxyls hydrogen-bonded to a few layers of water: a core-shell structure of
      C/PdO/OH/H2O. The conventional formulation Pd(OH)2/C from the macroscopic point
      of view is ruled-out by the different spectral signatures of surface hydroxyls
      and stoichiometric hydroxides. We also show that a minor fraction of the
      palladium is present as a reduced species. 

PMID- 25607380
TI  - In vivo evaluation of Fe3O4 nanoparticles.
AB  - Our review summarizes the latest approaches regarding in vivo biocompatibility
      evaluation of magnetite nanoparticle-based systems. The paper follows the
      applications of Fe3O4 nanoparticles in cancer diagnosis and treatment, by means
      of nanoparticle-mediated magnetic hyperthermia, respectively by targeted delivery
      of chemotherapeutics. The long-term biodistribution in relevant organisms is also
      discussed, due to the need of knowing the exact course of magnetite nanoparticles
      after the fulfillment of their function. Several commercial Fe3O4 systems used as
      contrast agents for medical imaging and cancer treatment by hyperthermia are
      briefly presented in the last section. 

PMID- 25607381
TI  - Molecular diagnosis of autoimmune skin diseases.
AB  - A wide range of skin diseases are associated with autoimmune responses against
      skin-specific or ubiquitous antigens. In many of these diseases, including
      autoimmune blistering disorders, collagenoses and vasculitides, extensive
      clinical and experimental evidence shows that autoreactive T-cells and/or
      autoantibodies play a major pathogenic role, allowing their classification as
      autoimmune diseases. The presence of tissue-bound and circulating autoantibodies
      does not only bear relevance for disease pathogenesis, but also allows developing
      robust diagnostic tools and molecular therapeutic approaches. Thus, various
      immunofluorescence methods, as well as molecular immunoassays, including enzyme
      linked immunosorbent assay and immunoblotting, belong to the modern diagnostic
      algorithms for these disorders. This review article describes the
      immunopathological features of autoimmune skin diseases and the molecular assays
      currently available for their diagnosis and monitoring.

PMID- 25607382
TI  - Microvesicles - potential biomarkers for the interrelations atherosclerosis/type
      2 diabetes mellitus.
AB  - Microvesicles, also called microparticles or exosomes, are ultrastructural
      cellular components that have been widely researched in the past as well as
      present in order to establish their morphology, origin and role in physiological
      and pathological processes. Advanced techniques show that these microparticles
      have their clinical implications in the prevention and prediction in pathology
      and have potential in the discovery of novel therapeutic approaches to metabolic
      diseases such as diabetes, cardiovascular, autoimmune diseases and cancer. 

PMID- 25607383
TI  - Hepatic steatosis background in chronic hepatitis B and C - significance of
      similarities and differences.
AB  - The aim of our study was to investigate comparatively the steatotic background in
      viral chronic hepatitis B, C and mixed types, in correlation with the severity
      degree of specific liver lesions. The study group consisted of 1206 liver biopsy
      specimens, etiologically diagnosed as hepatitis C - 1021 (84.66%) cases,
      hepatitis B - 100 (8.29%) cases, hepatitis B and C - 39 (3.23%) cases, hepatitis
      B and D - 39 (3.23%) cases, hepatitis C and toxicity - six (0.49%) cases,
      hepatitis B, C and D - one case (0.08%). The histopathological assessment focused
      on the steatotic lesions associated with inflammation and fibrosis. The cases
      were classified according to necrosis and inflammatory activity (score between 0
      12) and fibrosis (score between 0-4). Our data indicates significant association
      of steatotic lesions in hepatitis C (76.59%) as opposed to other types of viral
      hepatitis. In mixed hepatitis B and C, steatotic lesions are more frequent
      (66.66%) than in chronic hepatitis B (47%) and in mixed chronic B and D hepatitis
      (48.72%). Steatosis was present in all cases with chronic hepatitis C and
      associated toxicity. These observations confirm the important aggressiveness of
      hepatitis C virus as opposed to hepatitis B and D virus. The analysis of the
      pattern of steatosis in correlation with necrosis and inflammatory activity and
      fibrosis, respectively, lead to the identification of certain specific elements.
      Thus, for all types of hepatitis, steatosis is associated predominantly with
      moderate severity (score 6-8) and progressive expansion of fibrosis (score 2-3).
      The presence of steatosis does not define hepatic lesions with severe
      inflammation (score 9-12) nor those with extended fibrosis (score 4). The type of
      steatosis present is mostly macrovesicular, the transformation into lipid cysts
      being uncommon. Based on the scoring systems applied in the evaluation of the
      entire investigated study group, we believe that a possible inclusion of a
      quantifiable criterion for steatosis could be beneficial in order to complete the
      characterization of the severity of the lesions, from the point of view of the
      potential for future evolution, reversible or irreversible.

PMID- 25607384
TI  - The immunohistochemical investigations of cadherin "switch" during epithelial
      mesenchymal transition of tongue squamous cell carcinoma.
AB  - Oral cancer was ranked as the sixth worldwide most common cancer, but recent
      studies noticed an overall downward trend in its incidence. However, for tumors
      localized on the tongue, the incidence seems to increase. The malignant
      transformation of many carcinomas is associated with loss of epithelial
      differentiation and gain of a mesenchymal phenotype, a process known as
      epithelial-mesenchymal transition (EMT) which for oral squamous cell carcinomas
      (OSCC) could be a predictor and a prognostic factor. The aim of our study was to
      investigate immunohistochemically the E-cadherin/N-cadherin "switch" and vimentin
      expression as markers of EMT process in tongue OSCC. Thus, we analyzed 15 cases
      of tongue OSCC by enzymatic double immunohistochemistry using the following
      double pairs of antibodies: E-cadherin/vimentin and N-cadherin/E-cadherin. E
      cadherin reactivity was recorded in all the investigated cases, the pattern of
      expression being both membranous and cytoplasmic, with the membrane pattern
      decreasing simultaneously with the decrease of the differentiation degree and
      with the increase of invasion phenotype, while the cytoplasmic pattern had an
      opposite behavior. Tumor parenchyma reactivity for vimentin was noticed in 73.3%
      and its expression was more obvious in tumor cells from the periphery of
      proliferative islands and in acantholytic carcinomatous cells. N-cadherin
      reactivity was restricted to only 33.33% of the investigated cases and its
      expression was prevalent in poorly differentiated forms. In conclusion, in tongue
      squamous cell carcinomas at the invasion front the E-cadherin reactivity
      decreases while vimentin expression increases, with a cytoplasmic N-cadherin
      reactivity in a few of the observed cases. This EMT phenotype was correlated with
      the decrease of differentiation degree, with the increase of the type of invasion
      pattern and with increasing disease' stages and thus these EMT markers could be
      used for prognostic stratification of such patients.

PMID- 25607358
TI  - Common genetic variants influence human subcortical brain structures.
AB  - The highly complex structure of the human brain is strongly shaped by genetic
      influences. Subcortical brain regions form circuits with cortical areas to
      coordinate movement, learning, memory and motivation, and altered circuits can
      lead to abnormal behaviour and disease. To investigate how common genetic
      variants affect the structure of these brain regions, here we conduct genome-wide
      association studies of the volumes of seven subcortical regions and the
      intracranial volume derived from magnetic resonance images of 30,717 individuals
      from 50 cohorts. We identify five novel genetic variants influencing the volumes
      of the putamen and caudate nucleus. We also find stronger evidence for three loci
      with previously established influences on hippocampal volume and intracranial
      volume. These variants show specific volumetric effects on brain structures
      rather than global effects across structures. The strongest effects were found
      for the putamen, where a novel intergenic locus with replicable influence on
      volume (rs945270; P = 1.08 * 10(-33); 0.52% variance explained) showed evidence
      of altering the expression of the KTN1 gene in both brain and blood tissue.
      Variants influencing putamen volume clustered near developmental genes that
      regulate apoptosis, axon guidance and vesicle transport. Identification of these
      genetic variants provides insight into the causes of variability in human brain
      development, and may help to determine mechanisms of neuropsychiatric
      dysfunction. 

PMID- 25607385
TI  - Detection of Merkel cell polyomavirus in formalin-fixed, paraffin-embedded tissue
      of Merkel cell carcinoma and correlation with prognosis.
AB  - Merkel cell carcinoma (MCC) is a rare, but highly aggressive primary cutaneous
      malignancy, showing neuroendocrine differentiation. In 2008, a novel member of
      the polyomavirus family, named Merkel cell polyomavirus (MCPyV) was identified in
      the genome of MCC tumors raising the possibility of an involvement in its
      pathogenesis. Due to the rarity of this tumor and current pathology practices,
      the most readily available tissue is archival formalin-fixed, paraffin-embedded
      (FFPE) material. In this study, we evaluated the presence of MCPyV in FFPE tissue
      and correlated its presence with tumor progression. Representative FFPE specimens
      from 18 tumors belonging to 14 patients with a diagnosis of MCC spanning the
      period from 2003 to 2008 were retrieved. Following DNA extraction, we performed
      PCR amplification and sequencing with four different MCPyV-specific primer pairs
      mapping within the T antigen and VP1 region. Overall, we detected MCPyV amplicons
      in 8/18 (44.4%) analyzed tumors from 7/14 (50%) cases. Two-year survival rate and
      median survival for the MCPyV-positive MCCs were 48% and 22.5 months,
      respectively and for the negative ones 69% and 51.3 months, respectively;
      however, the difference did not reach statistical significance (p=0.8). There was
      no significant correlation between the presence of the virus and the stage at
      presentation; however, tumors in the head and neck area had a lower frequency of
      viral positivity compared to those arising in the extremities suggesting a MCPyV
      independent oncogenetic pathway perhaps, dependent on UV exposure, in a subset of
      these cases.

PMID- 25607388
TI  - Bone marrow edema - premonitory sign in malignant hemopathies or nonspecific
      change?
AB  - Bone marrow edema (BME) is defined as an excess of fluids that builds up in the
      bone marrow (BM), commonly found because of osteoporosis, trauma, infections,
      ischemia or neoplasia. Histologically, BME is characterized by accumulation of
      extracellular eosinophilic fluid. Magnetic Resonance Imaging (MRI) is the only
      method that highlights the presence of BME caused by various diseases, including
      the one associated with hematological malignancies. The classic MRI protocol for
      the study of BM and BME includes T1- and T2-weighted sequences, the STIR
      sequence, and in some cases, the administration of intravenous contrast agents in
      T1-weighted sequences. Fifty-four patients were investigated; there were
      identified 30 patients with MRI features of BME. Out of the 30 patients with BME,
      24 were known to have a malignant hematological disease (multiple myeloma,
      leukemia, lymphoma); for the remaining subjects, imagistic findings and other
      laboratory investigations led to multiple myeloma diagnosis. Of the 30 patients,
      six showed characteristic lesions of the underlying disease as well as BME; four
      patients had only BME. BM is a structure that is commonly investigated using MRI
      scans, regardless of the examined bone segment. T1-weighted images and T2
      weighted with fat suppression are essential for BME evaluation. Moreover, MRI
      allows monitoring disease progression and treatment response in patients with
      malignant hemopathies. 

PMID- 25607387
TI  - Corpora amylacea in the brain form highly branched three-dimensional lattices.
AB  - Corpora amylacea (CA) are glycoprotein-based depositions that accumulate in the
      normal aging brain or consecutively to different neuro-degenerative diseases.
      Although controversies still exists in what it regards their origins and
      functions, their morphology is described simply as round basophilic entities
      based on bi-dimensional observations. The aim of the present study was to
      evaluate the three-dimensional morphology of these bodies in the brain in normal
      aging. We utilized here brain tissue from six aged patients, and performed an in
      depth stereological analysis of CAs based on series of thin serial sections, and
      50 MUm-thick sections. The thin seriate sections have been counter-stained with
      Hematoxylin and Eosin, while the thick sections have been immunostained in
      fluorescence for ubiquitin and GFAP/collagen IV or aquaporin 4. Three-dimensional
      renderings have been obtained after aligning the serial sections, while high
      resolution z-stacks have resulted after deconvolution on the thick sections. More
      than 70% of all the identified CAs proved to be in fact parts of larger
      aggregates, where the flattened individual spheroids branched and communicated
      with other bodies in a complex pattern, and budding of small CAs from larger CAs
      could be observed. There was a direct correlation between the diameter of the
      vessels and the number of associated CAs. Astrocyte GFAP and aquaporin 4 signals
      surrounded CAs, but without any colocalization with the ubiquitin areas, while
      perivascular CAs were sometimes enclosed in pockets of the basement membranes. In
      conclusion, as far as we know, this is the first study to describe the three
      dimensional branching complexity of corpora amylacea in the brain.

PMID- 25607386
TI  - Prognostic factors in anterior skull base meningiomas.
AB  - AIM: Histopathological and immunohistochemical study of prognostic factors in
      anterior skull base meningiomas in order to determine the post-operative
      management. MATERIALS AND METHODS: The studied material consisted in resection
      specimens from 65 patients with anterior skull base meningiomas hospitalized in
      Clinic of Neurosurgery, National Institute of Neurology and Neurovascular
      Diseases, Bucharest, Romania, and diagnosed in the Department of Pathology of the
      same Institute, between 2007 and 2013. The biological material was processed by
      standard histological technique with Hematoxylin and Eosin staining which allowed
      the classification of tumors according to WHO 2007 system and the assessment of
      the morphological parameters of known prognostic value. Subsequently, the tumor
      fragments were submitted to immunohistochemistry to evaluate the proliferative
      activity (Ki-67 labeling index) and progesterone hormone receptor (PR) status.
      RESULTS: 83.07% of the 65 anterior skull base meningiomas were WHO grade I
      tumors; the grade II tumors accounted 15.38%, while the grade III tumors were
      rare (1.53%). Mitotic activity was variable, reaching up to 14 mitoses/10 HPF
      (high-power field) in atypical and anaplastic tumors; mitoses were absent in
      64.81% of grade I tumors; the average mitotic index in grade II tumors was 5.15
      mitoses/10 HPF. Both mitotic activity and infiltrative and invasive tumor growth
      (the latter found in 36.92% of cases) were correlated with tumor grade. Ki-67
      labeling index ranged between 1.1% and 7.7%, with the highest value found in
      anaplastic tumor; progesterone receptors (PR) were expressed with variable index
      in 84.61% of cases. The immunonegative PR tumors were represented by 16.66% of
      grade I tumors and by the only grade III tumor. In contrast to PR, Ki-67
      expression was statistically correlated with tumor grade. The comparison between
      the expression of Ki-67 and PR revealed an inverse relationship between the level
      of PR expression and the proliferative activity intensity. CONCLUSIONS: We found
      that PR expression decreases as the biological behavior of tumor becomes more
      aggressive; it may be related with an increased risk of recurrence, making the
      postoperative surveillance more rigorous in these patients.

PMID- 25607389
TI  - Biopsying parapsoriasis: quo vadis? Are morphological stains enough or are
      ancillary tests needed?
AB  - BACKGROUND: Parapsoriasis represents a group of cutaneous disorders that shows
      variable clinical aspects somehow resembling to psoriasis, how is reflecting by
      its name. It was first named by Brocq, in 1902, as an entity with three
      components: pityriasis lichenoides, small plaque parapsoriasis and large plaque
      parapsoriasis. Nowadays, under the name of parapsoriasis are included only the
      last two categories, that are considered disorders characterized by the presence
      of a mononuclear infiltrate in the dermis, composed of T-cells. Until now, there
      were not established pathognomonic histopathological features to diagnose
      parapsoriasis. AIM: The aim of the study was to investigate the epidemiological
      and morphological data of parapsoriasis cases diagnosed at Emergency City
      Hospital, Timisoara, Romania for a period of 12 years. MATERIALS AND METHODS: The
      study had two parts; one was retrospective and another one prospective. For the
      retrospective part, we searched 210111 patient files recorded in our Pathology
      Service for a period of 11 years, from January 2002 to December 2012. The slides
      were searched from the archive and re-read by two individual pathologists. For
      prospective part of the study, we reviewed 11815 histological slides read between
      January and June 2013. After inspection of the recorded files, the pathologists
      noted, were available, the localization and number of the lesions, together with
      symptoms. The biopsied specimens were initially processed with routine
      histological technique, the archive slides being stained with Hematoxylin and
      Eosin. While reading the slides, the pathologists paid attention to the
      architecture of the epidermis, the presence of epidermotropism and interface
      dermatitis, type of the dermal infiltrate and its distributions. CONCLUSIONS: In
      the present study, we emphasized the histopathological aspects of parapsoriasis
      in order to create a basic line that could help in the establishment of a
      uniformly accepted definition of parapsoriasis on histopathological grounds.

PMID- 25607390
TI  - Alveolar and dental arch morphology in Angle Class II division 2 malocclusion: a
      comparative study.
AB  - OBJECTIVE: The aim of this study was to analyze the dental and alveolar
      intercanine, interpremolar and intermolar widths in patients with Class II/2
      malocclusion and to compare the data with a patient group with normal occlusion
      and also with a patient group with Class II/1 malocclusion. MATERIALS AND
      METHODS: The study was conducted on 140 untreated patients with permanent
      dentition, aged 16 to 25 years, which were divided into three groups, according
      to Angle's classification of occlusion. The measurements of the dento-alveolar
      intercanine, interpremolar and intermolar widths were made on virtual study
      models, scanned using an optical 3D scanner. The unpaired (Student's) t-test was
      used to determine whether there were any significant differences between the
      Class II/2 and Class I groups and between Class II/2 and Class II/1 groups,
      respectively (p<0.05). RESULTS: Significant differences were found between Class
      II/2 and Class II/1 groups in the maxillary and mandibular intercanine widths.
      Comparing the Class II/2 and Class I groups, significant differences were found
      in the mandibular intercanine width, in the maxillary and mandibular
      interpremolar widths and also in the maxillary and mandibular intercanine and
      interpremolar alveolar widths. CONCLUSIONS: The maxillary and mandibular
      interpremolar widths and the intercanine and interpremolar alveolar widths were
      larger, while the mandibular intercanine width was shorter in the Class I group
      than in the Class II division 2 group. The mandibular intercanine width was
      longer and the maxillary intercanine width was shorter in the Class II division 1
      group compared to the Class II division 2 group.

PMID- 25607391
TI  - The anatomo-radiological study of unusual extrasinusal pneumatizations: superior
      and supreme turbinate, crista galli process, uncinate process.
AB  - INTRODUCTION: One of the aspects that have an influence on rhinosinusal
      endoscopic surgery is extrasinusal pneumatization, which can also affect less
      common structures at this level. The pneumatization of the superior and supreme
      turbinates, uncinate process and crista galli are perfect examples of this
      situation. The diagnosis is made only through imaging methods. MATERIALS AND
      METHODS: This is a retrospective anatomo-radiological study analyzing 205 CT
      scans of the facial sinuses performed over a three years period. All patients
      were symptomatic and the CT scans were performed to assess the cases prior to
      surgery. Ninety-seven patients were females and 108 males, aged between 18 and 91
      years. RESULTS: The prevalence of pneumatization and the prevalence of the
      different pneumatization types (superior and supreme turbinate, uncinate process
      and crista galli) were determined. CONCLUSIONS: The pneumatization of the supreme
      turbinate (10.24%) was less common than that of the superior turbinate (29.76%)
      and affected all its anatomical variations (A, B, C). Pneumatization of the
      crista galli process was recorded in 22.92% of the cases, especially in
      association with type 2, while the prevalence of pneumatized uncinate process was
      of only 3.41% (uni- or bilateral).

PMID- 25607392
TI  - Analysis of aortic size in subjects died due to cardiovascular and non
      cardiovascular events: a necropsy study.
AB  - Aortic size is known to be a predictor for cardiovascular deaths. The purpose of
      this study was to investigate whether aortic diameters measured on tissue samples
      obtained during autopsy from subjects that died of cardiovascular disease were
      bigger when compared to those from subjects deceased from other cause than
      cardiovascular disease. The study included 91 deceased subjects (average age 56
      +/- 18.1 years), which underwent autopsy to determine cause of death.
      Morphological measurements were completed on 364 aortic specimens obtained from
      four different sites, namely ascending aorta, aortic arch, distal thoracic aorta
      and abdominal aorta. Aorta showed the tendency to decrease in diameter from
      ascending aorta to abdominal aorta, the latter presenting with the smallest
      diameter. All studied aortic diameters were found to be larger in the
      cardiovascular population (p<0.01).

PMID- 25607393
TI  - A morphometric study of multiple renal arteries in Greek population and a
      systematic review.
AB  - The aim of the study was to determine the distribution patterns of multiple renal
      arteries, evaluate how they are affected by gender and bilateral asymmetry and
      proceed on a systematic review. Two hundred and six kidneys from 103 Greek
      cadavers (53 males and 50 females) were investigated. The number and pattern of
      multiple renal arteries were determined according to side, gender and level of
      origin. The distances between the main renal and first multiple renal arteries
      were also measured. Multiple renal arteries were present in 11.2% of the kidneys.
      No statistically significant difference was found between side and gender
      (p>0.05). The incidence of multiple renal arteries was 87% unilaterally and 13%
      bilaterally. As regards the multiple renal arteries, a single artery was detected
      in 83%, two in 13% and three in 4.3%. In 30.4% (7/23) of the kidneys, there was a
      short common trunk (<1.5 cm), early dividing into the main renal artery and a
      thinner artery. Multiple renal arteries on the left side seemed to emerge lower
      than the right ones and displayed a greater variability at their origin. In the
      systematic review, we detected the patterns of multiple renal arteries which were
      classified according to population, gender, side and specimen (cadaveric,
      radiological or transplant). The awareness of morphology and topography of the
      multiple renal arteries is important in order to achieve a safe pre and
      intraoperative management of the renal vascular supply.

PMID- 25607394
TI  - Etiopathogenetic, clinical and histopathological aspects regarding the
      involvement of dental focal infection in premature births with fetal hypotrophy.
AB  - The study conducted on a total of 1344 preterm births, of which 403 hypotrophic
      fetuses births (between 2010-2012 within the Maternal Clinics of Craiova,
      Romania), studied the involvement of dental inflammatory infections in the
      chorioamnionitis onset. The possibility of transferring germs, toxins and
      degraded materials into the blood flow, and them entering the chorioamniotic
      structures is quite a common issue. Subclinically often evolving chorioamniotic
      membrane and its existence is clearly established after birth by
      histopathological and bacteriological examinations, being partially responsible
      for the growth delay of the conception product. Our study revealed this fact, by
      using clinical examinations, ultrasound exams, bacteriological determinations of
      the amniotic fluid and the placenta, alongside the histopathological
      examinations. The chorioamnionitis inflammatory process is responsible for
      premature birth, through a high synthesis of interleukins (IL) and
      prostaglandins, causing uterine contractions. Our IL-6 dosage determinations show
      its growth that can be considered a prediction marker for preterm birth. 

PMID- 25607395
TI  - Immunohistochemical analysis in the diagnosis of uterine myometrial smooth muscle
      tumors.
AB  - Uterine myometrial smooth muscle tumors sometimes raise concerns related to their
      histopathological typing, and that especially for benign entities with areas of
      atypia. In this study, we analyzed a group of myometrial smooth muscle tumors in
      what it regards their differential diagnosis utilizing a panel of antibodies
      consisting of alpha-SMA, Ki-67, p16, p53, PR and bcl-2. The study included a
      total of 16 cases of cellular leiomyomas, five cases of atypical leiomyomas and
      six of leiomyosarcomas, which were all analyzed for age, risk factors, mitotic
      activity, cellular atypia and tumor staging. In cases of cellular leiomyomas, the
      immunophenotype was characterized by high expression of PR and bcl-2 and low
      expression of p53 and Ki-67. For atypical leiomyomas, PR, bcl-2 and p53
      expression levels were highly compared with low levels of p16 and Ki-67.
      Leiomyosarcomas immunophenotype was characterized by high expression values of Ki
      67, p16 and p53, and decreased levels of PR and bcl-2. The study indicated
      specific immunophenotypes among the uterine myometrial smooth muscle tumors
      analyzed. The antibody panel used here might be a useful for the complementary
      histopathological analysis of myometrial leiomyomas and leiomyosarcomas. 

PMID- 25607396
TI  - Matrix metalloproteinase -7, -8, -9 and -13 in gingival tissue of patients with
      type 1 diabetes and periodontitis.
AB  - There is scientific data to support the existence of a two-way relationship
      between diabetes and periodontitis, with diabetes increasing the risk for
      periodontitis, and periodontal inflammation negatively affecting the diabetic
      status. Our study aims to investigate the expression of MMP-7, -8, -9 and -13 in
      the gingiva of the young patients with aggressive periodontitis (AP) and type 1
      diabetes mellitus (T1D). Gingival biopsies were harvested from five adult
      patients aged 19-29 years with T1D+AP with moderate (three cases) to severe (two
      cases) forms of AP and from four adult patients aged 18-28 years with moderate AP
      without T1D. The MMP-7 immunoreaction was positive in the five cases with T1D+AP
      with different staining patterns. The MMP-8 immunostaining was positive in all
      cases. The reaction was more intense in cases with T1D+AP, especially in those
      with severe periodontitis. The MMP-9 immunoreaction was present in all the
      structures of the gingival mucosa with different intensity, being frequently
      present surrounding the blood vessels of the chorion. In most of the patients,
      reaction to MMP-9 was intense, localized at the level of the cells in the
      superficial chorion and very rarely at the level of some dispersed cells in the
      connective vascular islands. MMP-13 was present in all cases, but it was more
      intense in the two cases with T1D+AP with probing depth (PD)>6 mm when it had
      similar patterns as MMP-9 staining and in one case with AP when the staining was
      observed strictly in the lamina propria associated with moderate chronic
      inflammatory infiltrate. The expression of MMP-7, -8, -9 and -13 in the gingiva
      of the young patients with aggressive periodontitis and T1D was positive in all
      studied cases supporting the hypothesis that both are inflammatory diseases with
      common pathogenic mechanisms involving inflammatory mediators and may be possible
      biomarkers of disease status.

PMID- 25607397
TI  - Cytoarchitecture of steroid dependent target tissues after testosterone
      administration compared to nandrolone decanoate in castrated rats in the aim of
      Hershberger bio test.
AB  - The objective was the cytoarchitecture evaluation of known steroid dependent
      target tissues after administering of testosterone, compared to action of its
      more active ester, nortestosterone (nandrolone decanoate) in castrated rat males
      in the aim of Hershberger bio test. Study was performed on 30 castrated male
      Wistar rats, aged between 35 and 39 days, in peripubertal period, divided into
      five groups. Androgen doses administration begun at the rats' age of 49 days.
      Animals were injected i.m., daily, for 10 consecutive days as follows: Aquatest
      (Balkan Pharmaceuticals Ltd., Moldova) testosterone aqueous solution:
      Testosterone I group (0.4 mg/animal); Testosterone II (0.8 mg/animal); (Deca
      Durabolin, Balkan Pharmaceuticals); nandrolone decanoate oily solution:
      Nortestosterone I (1.5 mg/kg body weight); Nortestosterone II (7.5 mg/kg body
      weight) and Control (White sesame oil, Manicos, Romania, 0.1 mL/animal).
      Gonadectomy (GDX) induced modifications of target tissues wet weight accompanied
      by important modifications in cytoarchitecture. Changes following exogenous
      administration of testosterone and nortestosterone decanoate were found in: liver
      (granular dystrophy, mega-mitochondria, tubular intumescences), prostate
      (increasing of the structural elements), seminal vesicles (hyalinosis, thickening
      of cell walls and the hyaline presence), levator ani-bulbo-cavernosus muscle
      (muscle fibbers dilacerations), bulbourethral glands (muscular fibbers
      rarefaction by fluid accumulation) demonstrating the disruptor activity
      especially for overdosed nandrolone decanoate.

PMID- 25607398
TI  - Histopathological study of pleomorphic adenoma of salivary glands.
AB  - The pleomorphic adenoma, also known as mixed tumor, presents an epithelial and
      mesenchymal histological structure, being also called epithelioma with altered
      stroma. The pleomorphic adenoma has a frequency of 70% of major salivary gland
      tumors, being located preponderantly at the level of parotid gland (52-84%), at
      the level of submandibular glands (7-17%) and at the level of the other salivary
      minor salivary glands (3-8%). The purpose of our study was the histopathological
      analysis of 45 cases of pleomorphic adenoma. The tumors were characterized by an
      increased structural pleomorphism, given by the multitude of cytological
      differences and proliferation patterns, and on the other side by the diversity of
      stromal component. 

PMID- 25607399
TI  - Prenatal depression and stress - risk factors for placental pathology and
      spontaneous abortion.
AB  - Prenatal stress and depression affects 10-25% of pregnant women and is associated
      with disruption of fetal neurodevelopment, higher rates of placental
      abnormalities, preeclampsia, spontaneous abortion, or preterm birth. Markers of
      genetic vulnerability are catechol-O-methyltransferase, monoamine oxidase-A,
      variation of serotonin transporters, low levels of dopamine-beta-hydroxylase, and
      brain derived neurotrophic factor Val66Met (BDNF), while hyperactivity of HPA
      (hypothalamic-pituitary-adrenal) axis and massive release of endogenous cortisol,
      regulated by metalloproteinase-1, -2, -3 and -9, and are involved both in
      depressive symptoms and neurodevelopmental abnormalities in fetus. In women with
      prenatal stress and depression which suffered spontaneous abortion were observed
      placental abnormalities as regular shape and necrotic villi, decidua with large
      areas of necrosis, acute inflammation and effusion areas correlated with increase
      in proinflammatory factors, immune deficit and infections, hyaline type fibrosis,
      intervilos and deciduous intense hemorrhage, associated with increase of vascular
      endothelial growth factor. Taking into account the important societal and
      economic costs becomes important for an interdisciplinary approach, in which
      pregnancy and its risks are a central point for women mental health. 

PMID- 25607400
TI  - The place of prostate rebiopsy in the diagnosis of prostate cancer.
AB  - AIM: To highlight the role of prostate rebiopsy in the diagnosis of prostate
      cancer (PCa) in cases with an atypical small acinar proliferation (ASAP)
      diagnosis on the initial biopsy. MATERIALS AND METHODS: A retrospective study on
      1525 patients who underwent prostate needle biopsy (PB) over a period of four
      years (2009-2012) was performed. For each patient the following were analyzed:
      age, prostate volume, digital rectal examination (DRE), serum total prostate
      specific antigen (tPSA), number of the cores taken. All PB were examined in HE
      staining and in difficult cases, immunohistochemistry (IHC) for basal cell
      markers was performed in order to establish a correct diagnosis. According to
      morphological criteria and IHC results, all PB were classified into four category
      of diagnosis: PCa, ASAP, high-grade prostate intraepithelial neoplasia (HGPIN)
      and benign (including normal tissue, inflammatory lesions, and prostatic
      atrophy). In ASAP cases, a rebiopsy was performed. RESULTS: PCa detection on the
      first biopsy was 69.77%, with a 3% incidence of ASAP and 1% of HGPIN, values
      similar with those in the literature. After rebiopsy the overall detection rate
      of PCa was improved to 71.01%, with a detection rate of 41.17% on the second
      biopsy. CONCLUSIONS: PCa diagnosis is the result of a complex algorithm including
      DRE, tPSA, transrectal ultrasound (TRUS) examination and TRUS-guided prostate
      biopsy. TRUS-guided prostate biopsy is the key step of this algorithm; it
      confirms the diagnosis of PCa and must be repeated in cases with a solid clinical
      suspicion of PCa, whenever histopathological features are inconclusive even after
      IHC staining.

PMID- 25607401
TI  - Meckel's diverticulum in children, clinical and pathological aspects.
AB  - Meckel's diverticulum (MD) represents one of the most common malformations of the
      digestive tract, being a vestige of the proximal end of omphalo-mesenteric duct,
      which normally obliterates and atrophiates between the sixth and ninth week of
      intrauterine life. It is estimated that 2-4% of people are carriers of this
      malformation. The interest in this organ study lies in the fact that it presents
      its own non-specific pathology, mimicking a cecal, colon or small intestine
      pathology. It seems that most MD cases are asymptomatic (AS MD), being arbitrary
      discovered during surgeries, whereas only a small part are being symptomatic (S
      MD). MD may be clinically expressed at any age but it is more common in children.
      In our study, we evaluated a group of 44 children, aged between 0 and 16 years,
      diagnosed with AS MD (15 cases) or S MD (29 cases). Of the 29 S MD cases, 14 had
      intestinal obstruction, seven cases showed lower gastrointestinal bleeding, five
      cases presented acute inflammation (diverticulitis) and three cases were
      complicated with peritonitis; 15 cases of AS MD were discovered during surgical
      interventions for acute appendicitis (14 cases) or inguinal hernia (one case).
      Most cases of MD were recorded between 1-4-year-old and 7-16-year-old. 

PMID- 25607402
TI  - A rare case of multiple clear cell acanthoma with a relatively rapid development
      of the lower legs.
AB  - Clear cell acanthoma, firstly described by Degos as "an epidermal tumor with a
      particular aspect", although quite a rare lesion, raised an important interest
      because it may be easily confused with other dermatologic lesions, in the absence
      of a histopathological examination. Its clinical aspect is of a solitary nodule,
      with a red-brown varying color, with a size of 3 mm to 2 mm, sometimes covered
      with a thin scall. We present a case of a multiple rare cell acanthoma (seven
      nodular formations), having a rapid development (about two months) diagnosed in a
      71-year-old patient within the lower 1/3 of the right shin.

PMID- 25607403
TI  - Seven renal arteries: a case report using MDCT angiography.
AB  - We report an atypical case of a 63-year-old male with the presence of seven renal
      arteries (RAs) (three right and four left) found incidentally on multi-detector
      computed tomography (MDCT) angiography which was used to investigate peripheral
      vascular disease of the lower limbs. Each arterial lumen was analyzed for the
      diameter at its origin; length and trajectory in the frontal plane (ascendant +
      or descendant -); and the distance between the point of origin from the abdominal
      aorta (AA) to its renal intraparenchymal penetration point. We also analyzed the
      distance between the extreme points of origin of the right and left RAs from the
      AA and the distance between the extreme points of penetration into the renal
      parenchyma of the right and left RAs. On each side, the endoluminal diameter at
      the origin of the main RA was significantly larger than that of the other AdRAs;
      however, the AdRAs were much longer than that of the main RA. From the six AdRAs,
      four were hilar RAs and two were superior polar RAs. Knowledge of such cases is
      of great clinical significance, as it may be beneficial in various urological
      operations or invasive arterial procedures. 

PMID- 25607404
TI  - Ordinary symptom for a serious pathology - giant solitary fibrous tumor of the
      pleura.
AB  - The solitary fibrous tumor of the pleura (SFTP) is a rare primary tumor arising
      from mesenchymal cells in the areolar tissue subjacent to the mesothelial-lined
      pleura. From an epidemiological standpoint, solitary fibrous tumors of the pleura
      account for less than 5% of primary pleural tumors, and commonly affect patients
      in the sixth and seventh decades. We presented the case of a 38-year-old woman,
      without any significant pathological history, who presented at the emergency room
      for unspecific respiratory symptoms. Imagistic investigations showed a giant
      opacity in the upper half part of the left hemithorax. The patient underwent
      surgery and en bloc resection of the tumor (30/25 cm) in oncological limits was
      performed. Definite diagnosis - solitary fibrous tumor of the pleura - was
      obtained through histological examination and immunohistochemistry. Even if SFTP
      are benign tumors, a long follow-up period is mandatory as even patients with
      complete resection are at risk of recurrence several years after surgery.

PMID- 25607405
TI  - In vivo imaging techniques for psoriatic lesions.
AB  - Psoriasis is an inflammatory skin disease, with a polymorphic clinical
      appearance. Modern techniques for in vivo imaging of skin structure, such as
      reflectance confocal microscopy (RCM) and dermoscopy, could be very useful tools
      for diagnosis and monitoring of psoriatic lesions. We report a case of psoriasis
      vulgaris in which we identified certain dermoscopic features suggestive for
      psoriasis and RCM enabled us to identify in vivo most of the histological
      features of psoriatic lesions. 

PMID- 25607406
TI  - A rare case of canine anomaly - a possible algorithm for treating it.
AB  - Canine transmigration is a very rare dental anomaly in which an unerupted
      mandibular canine migrates, crossing the mandibular midline. This unusual
      condition is most often diagnosed by chance during a routine X-ray examination.
      The most common clinical signs announcing the presence of this anomaly are over
      retention of the deciduous canine and the absence of permanent canine from the
      dental arch after its physiological period of eruption. In this paper, we present
      a clinical case, 10-year-old boy, who was diagnosed with mandibular right canine
      transmigration at three years after the start of orthodontic treatment, during
      which we were expecting the eruption of mandibular canines. The orthopantomograph
      revealed the mandibular right canine to be in a horizontal position under the
      apices of the incisors - type 2 transmigration pattern classified by Mupparapu
      (2002). Based on cone-beam computer tomography examination, we recommended a
      surgical exposure of the canine and orthodontic alignment. Due to the risk of
      root resorption of the mandibular right lateral incisor during orthodontic
      movement phase of canine transmigrated to the dental arch, we decided to align
      the mandibular right canine in a transposition, between the two mandibular right
      incisors. Then we resorted to adapting the mandibular right lateral incisor
      coronary morphology to simulate a canine and also to reshaping the canine
      coronary morphology to resemble a lateral incisor. This therapeutic approach
      allowed us to restore morphologically and functionally the mandibular dento
      alveolar arch, preserving the entire dental system.

PMID- 25607407
TI  - Frontal epidural empyema (Pott's puffy tumor) associated with Mycoplasma and
      depression.
AB  - A 37-year-old male has left exophthalmia, which gradually evolved in the last two
      years, finally with a deviation of left eye (LE), down side and out, with
      gradually decrease of visual acuity (VA). These symptoms are accompanied with
      headache and psychiatric manifestations with irritability, decreased attention,
      anxiety, insomnia, depressed mood. Brain Computed Tomography (CT) shows a tumor
      mass in air leakage sinus, bilateral frontal and bilateral ethmoidal, with left
      orbital invasion. This tumor mass lysis by pressure the supero-posterior wall of
      the left orbit, with the delimitation of a frontal epidural process with a
      capsule and calcifications. Additionally, it has been shown there is a bilateral
      maxillary sinusitis. The surgical intervention removed the infection focal spots
      rearranging the left eyeball, recovering the VA. The sinuses were drained. The
      psychiatric symptoms in the post operatory phase disappeared. Histopathological
      examination of the excised tissue revealed sinus ciliated respiratory mucosa with
      mixed acute and chronic inflammatory infiltrate and focal squamous metaplasia.
      The lamina propria is edematous and contains large numbers of neutrophils,
      lymphocytes and plasma cells. Histopathological diagnosis is acute and chronic
      sinusitis. CONCLUSIONS: An untreated infection of the aerial sinuses can lead to
      a complication like Pott's puffy tumor. When signs such as ophthalmologic,
      psychiatric and intense headaches appear, it suggests the presence of the Pott's
      puffy tumor (PPT). The clinical signs are reversible once the tumor has been
      removed.

PMID- 25607408
TI  - The role of immunohistochemistry in diagnosing a synchronous colon tumor.
AB  - Simultaneous presence of an epithelial and lymphoid tumor of the digestive tract
      is quite rarely met in literature. In this paper, we describe a case which
      presented such an association. Diagnosis was established by histological study,
      followed by immunohistochemistry. It is a synchronous colon tumor, associating a
      non-Hodgkin's lymphoma to a colon adenocarcinoma. The 57-year-old male patient
      has been clinically diagnosed with a tumor of the left abdominal quadrant and
      paraclinically (imaging and endoscopic) with colon neoplasm. Exploratory
      laparotomy revealed two tumors: one tumor of five centimeters in the sigmoid,
      with firm consistency, mobile on lower plans and the second tumor in the ceco
      ascending colon, measuring about 7 cm, irregular, with firm consistency, mobile
      on lower plans, with lymph nodes extending to retroperitoneal space. The urinary
      bladder, kidneys, liver and stomach were of normal aspect. Subtotal colectomy was
      performed with latero-lateral ileo-sigmoid anastomosis. Microscopic examination
      revealed sigmoid tumor as G1 adenocarcinoma and cecal tumor as B-cell type
      lymphoma. Immunohistochemistry established the final diagnosis of cecal
      localization being a diffuse immunoblastic large B-cell non-Hodgkin's malignant
      lymphoma. The final diagnosis of this patient was actually a synchronous
      manifestation of a colon adenocarcinoma and non-Hodgkin's lymphoma. This
      association puts into question synchronous tumors etiopathogeny matter.

PMID- 25607409
TI  - The impact of melanocytic cell destruction in pediatric facial burns and plastic
      surgery therapeutic management.
AB  - The main role of the melanin production belongs to the keratinocyte-Langerhans
      melanocyte complex that within a burn injury might be destroyed. A particular
      aspect has the pediatric patient with burns due to a deficit in pigment synthesis
      and particularities involving the growth process of facial structures. This
      article presents four eloquent cases of pediatric patients with sequelae,
      consequence of facial burns that varied in depth and etiology. The age of
      patients at time of admission was between four and 18 years, and the interval
      between production of the primary lesion and admission was variable (0-17 years).
      Conservative treatments prove to be insufficient, requiring the destroyed
      structures to be replaced with compatible tissue by surgical intervention. The
      therapeutic success of skin grafts and dermal substituents acknowledges the main
      role of plastic surgery. New technologies as well as new cell focused studies
      support the clinical proven results as well as they enlarge the spectrum of
      potential available therapeutic methods in order to obtain the best therapeutic
      results. 

PMID- 25607410
TI  - Aneurysmal dermatofibroma mimicking both clinical and dermoscopic malignant
      melanoma and Kaposi's sarcoma.
AB  - Aneurysmal dermatofibroma (AD) or aneurysmal fibrous histiocytoma (AFH) is a
      relatively rare form of histiocytoma representing less than 2% of total cases. It
      shares many clinical and dermoscopic similarities with skin tumors, especially
      malignant melanoma and Kaposi's sarcoma, which can make differentiation
      problematic. We report the case of a 53-year-old man, who presents with a black
      nodular tumor with increased consistency, edges infiltrated from the surface to
      depth, spontaneous and sensitive to touch that shows rapid growth in the last
      three months. Dermoscopically, the central region consists of intricate areas
      colored in red, violet, blue-white and black. On the periphery stand two rings,
      centrally white and peripherally pigmented, with an abundance of polymorphic
      capillaries. To clarify the diagnosis, the lesion was widely excised and
      histopathological examination was performed, which revealed immunophenotypical
      tumor cells negative for HMB-45 and S100, and numerous CD68 macrophages between
      tumor cells. This aneurysmal fibrous histiocytoma shows both clinical and
      dermoscopically discrete differential criteria, which are not specific and that
      make it difficult to distinguish from malignant melanoma and Kaposi's sarcoma,
      and required performing histopathology and immunohistochemistry. 

PMID- 25607411
TI  - Adenoid basal carcinoma-like tumor combined with invasive squamous cell carcinoma
      foci of uterine cervix - a case report of 55-year-old woman with literature
      review.
AB  - BACKGROUND: Adenoid basal carcinoma (ABC) of uterine cervix is an extraordinary
      example of carcinoma with both basal and glandular cell types. Here we present
      such a case of ABC combined with invasive squamous cell carcinoma (SCC) of 55
      year-old woman. METHODS: The tumor was stained with Hematoxylin-Eosin (HE),
      Mucicarmine, PAS/Alcian Blue, CK AE1/AE3, CK7, CD117 and Ki67. RESULTS: The
      whitish-grey 1 cm in-depth infiltration of endocervix was composed of
      infiltrative coalescing areas of CK AE1/AE3 positive carcinoma with peripheral
      palisading of basal cell type with spaces lined by Mucicarmine- and Alcian Blue
      positive benign looking, glandular epithelium. There were also foci of apparently
      malignant squamous epithelium with evident dyskeratosis. Thus, a lesion was
      diagnosed of adenoid basal carcinoma combined with invasive squamous cell
      carcinoma foci of uterine cervix. The tumor was further CD117 negative what
      favored diagnosis of ABC over adenoid cystic carcinoma (ACC). There were rare
      mitoses on HE slides but 60% of all tumor cells were positive for Ki67 that would
      partially contradict reported benign nature of ABC lesion. Moreover, tumor was
      CK7-positive and this finding was controversial and according to one report
      favored diagnosis of ABC-like adenosquamous carcinoma (ACC). Due to CK7
      positivity and high index of Ki67, the neoplasm was re-classified as adenoid
      basal carcinoma-like tumor. CONCLUSIONS: It seems reasonable to treat the patient
      in the same manner as in case of pure simple invasive squamous cell carcinoma
      because much more aggressive, minor component of invasive SCC was found within
      ABC in our case.

PMID- 25607412
TI  - Thermographic and microscopic evaluation of LARS knee ligament tearing.
AB  - Damage to knee articular ligaments causes important functional problems and
      adversely affects particularly the stability of the knee joint. Several methods
      were developed in order to repair damage to the anterior cruciate ligament (ACL),
      which employ autografts, allografts, as well as synthetic ligaments. One such
      synthetic scaffold, the ligament advanced reinforcement system (LARS) synthetic
      ligament is made of non-absorbing polyethylene terephthalate fibers whose
      structure allow tissue ingrowths in the intra-articular part, improving the
      stability of the joint. The LARS ligament is nowadays widely used in modern knee
      surgery in the Europe, Canada, China or Japan. This paper evaluates LARS ligament
      from two perspectives. The first regards a study done by the Orthopedics Clinic
      II, Timisoara, Romania, which compared results obtained by employing two
      techniques of ACL repair - the Bone-Tendon-Bone (BTB) or LARS arthroscopic, intra
      articular techniques. This study found that patients treated with the BTB
      technique presented with an IKDC score of 45.82+/-1.14 units preoperative, with
      increasing values in the first nine months after each implant post-surgical
      ligament restoration, reaching an average value of 75.92 +/- 2.88 units
      postoperative. Patients treated with the LARS technique presented with an IKDC
      score of 43.64 +/- 1.11 units preoperative, and a score of 77.32 +/- 2.71 units
      postoperative. The second perspective describes the thermographic and microscopic
      analysis of an artificial knee ligament tearing or loosening. The objective of
      the study was to obtain information regarding the design of artificial ligaments
      in order to expand their lifespan and avoid complications such as recurring
      synovitis, osteoarthritis and trauma of the knee joint. Thermographic data has
      shown that tearing begins from the inside out, thus improving the inner design of
      the ligament would probably enhance its durability. An optical microscope was
      employed to obtain images of structural damage in the inner layers, for use in
      further analysis of the tears. In conclusion, the LARS artificial ligament, like
      the BTB technique, displays both advantages and disadvantages. It is important to
      understand that these two options of ACL lesion repair are not competing. LARS
      could, in addition to its use in primary ACL ruptures, be utilized in revisions
      of autologous graft rupture post primary ACL repair.

PMID- 25607413
TI  - Left crossed fused renal ectopia L-shaped kidney type, with double nutcracker
      syndrome (anterior and posterior).
AB  - Crossed fused renal ectopia (CFRE) is the second most common fusion anomalies
      (FAs) of the kidneys after horseshoe kidney. Crossed fused renal ectopia (CFRE)
      results from one kidney crossing over to the opposite side and subsequent fusion
      of the parenchyma of the two kidneys. We report, by multidetector-row computed
      tomography (MDCT) angiography, an extremely rare case of a left CFRE (L-shaped
      kidney type), consisting of multiple renal arteries (one main renal artery for
      the upper renal parenchyma, and three renal arteries (one main and two
      additional) for the lower renal parenchyma) and two left renal veins, which
      produced a double nutcracker syndrome (both anterior and posterior). The L-shaped
      left kidney has a maximum length of 18.5 cm, a maximum width of 10.2 cm, and a
      maximum thickness of 5.3 cm. The upper pole of the kidney is located at the level
      of the lower third of T12 vertebral body (4.6 cm left to the mediosagittal plan);
      the lower pole is located along the lower half of the L5 vertebral body (1.5 cm
      left to the mediosagittal plan). The following case will focus on the relevant
      anatomy, embryology, and the clinical significance of this entity. 

PMID- 25607414
TI  - Accessory spleen.
AB  - An accessory spleen (AS), or splenunculus, is a small nodule of splenic tissue
      found outside of the spleen. Post-mortem examinations, also known as autopsies,
      are carried out to identify a cause of death, and to assess the state of the
      organs of the deceased. We present two incidental cases of splenunculi, one
      localized in greater omentum and a second one localized in the hilum of the
      spleen, diagnosed during a histopathological examination. An immunohistochemical
      profile of the normal and accessory spleen was followed where the expression of
      the CD20, CD3, CD23, alpha-SMA were analyzed. 

PMID- 25607415
TI  - Oral squamous cell carcinoma of the maxilla, a second malignancy after a right
      ethmoido-maxillary chondrosarcoma.
AB  - Squamous cell carcinoma is defined as an invasive epithelial neoplasm, with
      variable degrees of squamous differentiation, with or without keratinization. It
      is origins stand at the level of the keratinized stratified squamous epithelium
      (skin) or non-keratinized (oral mucosa, esophageal mucosa, uterine exocervical
      mucosa), but it can also be found in squamous metaplasia areas (uterine
      endocervix or trachea-bronchial tree). This report presents the case of an oral
      squamous cell carcinoma as a second malignancy in the same anatomical territory,
      in a patient with prior treatment for chondrosarcoma, both surgical and
      radiotherapy. The tumor had appeared 5-6 months prior and had undergone a
      relatively rapid growth, this being the patient's main motive for addressing the
      doctors. The tumor was greyish, with imprecisely demarcated margins, of firm
      consistency, bleeding and with local necrotic deposits. The tumor extended from
      the incisive region to the maxillary tuberosity, towards the cheek mucosa and the
      soft palate. After a large excision, the histopathological diagnosis was
      infiltrative keratinizing squamous cell carcinoma, with moderate differentiation,
      with origins in the oral mucosa, infiltrating the whole of the maxilla and the
      maxillary sinus mucosa. Approximately three months after the surgery, a new tumor
      appeared in the oral cavity, on superior and inferior mucosa of the right cheek,
      extending towards the right buccal commissure, implying a relapse of the primary
      tumor. Postoperative oncological therapy included standard chemotherapy, which
      resulted in favorable postoperative evolution. This case is interesting by the
      association, of two metachronous malignant tumors, of different histological
      origin: a chondrosarcoma and a squamous cell carcinoma, at an interval of 25
      years. 

PMID- 25607416
TI  - Gastrointestinal stromal tumor, jejunal atresia and stenosis in a neonate.
AB  - Gastrointestinal stromal tumors could rise in different areas of the digestive
      tract, at any age, but very rarely in neonates. We present the case of a 5-day
      old male, with intestinal stenosis and atresia (type II) operated for
      peritonitis. On the resected specimen, the histopathological examination revealed
      a small gastrointestinal tumor of 8 mm. The immunohistochemical analysis
      indicated a low malignant potential. He is currently at two years of oncologic
      follow-up with no evidence of disease. 

PMID- 25607417
TI  - Thrombotic thrombocytopenic purpura: a hematological emergency.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disease
      characterized by mechanical hemolytic anemia and consumptive thrombocytopenia
      leading to disseminated microvascular thrombosis that causes signs and symptoms
      of organ ischemia and functional damage. TTP is diagnosed by the presence of
      microangiopathic hemolytic anemia and thrombocytopenia in a patient who
      frequently presents with central nervous system involvement and, to a lesser
      extent, renal dysfunction. CASE REPORT: We present the case of a 23-year-old
      female with TTP, diagnosed by the presence of the neurological symptoms,
      microangiopathic hemolytic anemia and severe thrombocytopenia (platelets
      4000/MUL). During the clinical evolution, the patient presented the hepatic
      cytolysis syndrome, following disseminated microvascular thrombosis inside the
      liver, representing an atypical damage. The diagnosis was difficult because it
      was necessary to make differential diagnosis with other diseases that evolve with
      microangiopathic hemolytic anemia in a short time to be able to initiate
      plasmapheresis. Initiation of the plasmapheresis as soon as possible was the goal
      of our treatment. Following the plasmapheresis combined with administration of
      corticosteroids was achieved complete resolution of all symptoms. CONCLUSIONS:
      TTP is a hematological emergency and diagnostic challenge. The critical
      determinant of outcome is timely diagnosis and treatment. Once the diagnosis is
      suspected, life-saving therapeutic plasma exchange therapy is initiated.

PMID- 25607418
TI  - Stress in medical students.
AB  - Stress has been defined as the state of a body threatened by imbalance under the
      influence of agents or conditions endangering its homeostatic mechanisms but the
      concept have multiple meanings in correlation with the origin and biological
      support of its effects. Also, stressors are multiple, recording one of the
      highest levels during the academic studies. For the medical students, stress
      represents an important challenge, especially during the first year of medical
      school, caused by the absence of a learning strategy, the sleepless night before
      the exam and also an unhealthy food intake during the exams. The coping
      strategies are important, their background being represented by the social
      support, especially within the family, and emotional, the passions of the
      medicine students being the most important stress-combating factor. Gender
      represents also an important factor for the stress vulnerability, manifested
      through medical and psychiatric symptoms. In order to train good doctors, fair
      and above all healthy, it is important to consider not only the information we
      want to transmit, but also the context in which we educate. 

PMID- 25607419
TI  - Celebrating Soft Matter's 10th Anniversary: chain configuration and rate
      dependent mechanical properties in transient networks.
AB  - Numerical solution of a coupled set of Smoluchowski convection-diffusion
      equations of associating polymers modelled as finitely extensible dumbbells
      enables computation of time-dependent end-to-end distributions for bridged,
      dangling, and looped chains in three dimensions as a function of associating end
      group kinetics. Non-monotonic flow curves which can lead to flow instabilities
      during shear flow result at low equilibrium constant and high association rate
      from two complementary phenomena: a decrease in the fraction of elastically
      active chains with increasing shear rate and non-monotonic extension in the
      population of elastically active chains. Chain tumbling leads to reformation of
      bridges, resulting in an increased fraction of bridged chains at high Deborah
      number and significant reduction in the average bridge chain extension. In the
      start-up of steady shear, force-activated chain dissociation and chain tumbling
      cause both stress overshoot and stress ringing behaviour prior to reaching steady
      state stress values. During stress relaxation following steady shear, chain
      kinetics and extension mediate both the number of relaxations and the length of
      time required for system relaxation. While at low association rate relaxation is
      limited by the relaxation of dangling chains and the rate of dangling chain
      formation, at high association rate coupling of dangling and bridged chains leads
      to simultaneous relaxation of all chains due to a dynamic equilibrium between
      dangling and bridged states. 

PMID- 25607420
TI  - Modeling uptake of hydrophobic organic contaminants into polyethylene passive
      samplers.
AB  - Single-phase passive samplers are gaining acceptance as a method to measure
      hydrophobic organic contaminant (HOC) concentration in water. Although the
      relationship between the HOC concentration in water and passive sampler is linear
      at equilibrium, mass transfer models are needed for nonequilibrium conditions. We
      report measurements of organochlorine pesticide diffusion and partition
      coefficients with respect to polyethylene (PE), and present a Fickian approach to
      modeling HOC uptake by PE in aqueous systems. The model is an analytic solution
      to Fick's second law applied through an aqueous diffusive boundary layer and a
      polyethylene layer. Comparisons of the model with existing methods indicate
      agreement at appropriate boundary conditions. Laboratory release experiments on
      the organochlorine pesticides DDT, DDE, DDD, and chlordane in well-mixed slurries
      support the model's applicability to aqueous systems. In general, the advantage
      of the model is its application in the cases of well-agitated systems, low values
      of polyethylene-water partioning coefficients, thick polyethylene relative to the
      boundary layer thickness, and/or short exposure times. Another significant
      advantage is the ability to estimate, or at least bound, the needed exposure time
      to reach a desired CPE without empirical model inputs. A further finding of this
      work is that polyethylene diffusivity does not vary by transport direction
      through the sampler thickness. 

PMID- 25607421
TI  - Age, wage, and job placement: older women's experiences entering the retail
      sector.
AB  - Older women seeking employment often find opportunities limited to low-wage jobs,
      such as those in retail. We report findings about job placement and starting
      wages for hourly workers hired at a women's apparel retailer from August 2006 to
      December 2009. We examine competing hypotheses regarding the role of age in
      explaining women's job placement and starting wages. Although newly hired women
      age 55+ earn higher wages and are placed in higher-quality jobs than the youngest
      women (ages 18-22), they are less likely to be placed in better-quality jobs than
      their midlife counterparts. Overall, wage differences are largely explained by
      job quality. 

PMID- 25607423
TI  - One-step chemical synthesis of ZnO/graphene oxide molecular hybrids for high
      temperature thermoelectric applications.
AB  - ZnO as high-temperature thermoelectric material suffers from high lattice thermal
      conductivity and poor electrical conductivity. Al is often used to n-dope ZnO to
      form Zn1-xAlxO (AZO). Owing to very limited Al solubility (less than 2 atom %) in
      AZO, however, electrical conductivity is difficult to improve further. Moreover,
      such a low concentration of Al dopants can hardly reduce the thermal
      conductivity. Here, we propose slightly adding chemically reduced graphene oxides
      (rGOs) to AZO in various contents to modulate the carrier concentration and
      simultaneously optimize the electrical and thermal conductivities. Such
      nanocomposites with rGO embedded in AZO matrix are formed on the molecular level
      by one-step solution chemistry method. No obvious changes are found in
      crystalline structures of AZO after introducing rGOs. The rGO inclusions are
      shown to uniformly mix the AZO matrix that consists of compacted nanoparticles.
      In such AZO/rGO hybrids, Zn2+ is captured by the rGO, releasing extra electrons
      and thus increasing electron density, as confirmed by Hall measurements. The
      phonon-boundary scattering at the interface between AZO and rGO remarkably
      reduces the lattice thermal conductivity. Therefore, a respectable thermoelectric
      figure of merit of 0.28 at 900  degrees C is obtained in these nanocomposites at
      the rGO content of 1.5 wt %, which is 8 times larger than that of pure ZnO and
      60% larger than that of alloyed AZO. This work demonstrates a facile wet
      chemistry route to produce nanostructured thermoelectric composites in which
      electrical conductivity can be greatly increased while largely lowering thermal
      conductivity, collectively enhancing the thermoelectric performance.

PMID- 25607424
TI  - Treating millions for HIV--the adherence clubs of Khayelitsha.

PMID- 25607425
TI  - Demedicalizing AIDS prevention and treatment in Africa.

PMID- 25607426
TI  - Bridging the hospitalist-primary care divide through collaborative care.

PMID- 25607429
TI  - Images in clinical medicine. Bilateral lower palpebral MALT lymphoma.

PMID- 25607430
TI  - Case records of the Massachusetts General Hospital. Case 3-2015. A 60-year-old
      woman with abdominal pain, dyspnea, and diplopia.

PMID- 25607428
TI  - Origins of cystic fibrosis lung disease.

PMID- 25607431
TI  - Institute of Medicine report on GME--a call for reform.

PMID- 25607427
TI  - Causes and timing of death in extremely premature infants from 2000 through 2011.
AB  - BACKGROUND: Understanding the causes and timing of death in extremely premature
      infants may guide research efforts and inform the counseling of families.
      METHODS: We analyzed prospectively collected data on 6075 deaths among 22,248
      live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born
      in study hospitals within the National Institute of Child Health and Human
      Development Neonatal Research Network. We compared overall and cause-specific in
      hospital mortality across three periods from 2000 through 2011, with adjustment
      for baseline differences. RESULTS: The number of deaths per 1000 live births was
      275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285
      (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI,
      248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three
      periods). There were fewer pulmonary-related deaths attributed to the respiratory
      distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003
      and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78
      to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as
      compared with 2000-2003, there were decreases in deaths attributed to immaturity
      (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system
      injury (P<0.001); however, there were increases in deaths attributed to
      necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27],
      P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3%
      occurred after 28 days. CONCLUSIONS: We found that from 2000 through 2011,
      overall mortality declined among extremely premature infants. Deaths related to
      pulmonary causes, immaturity, infection, and central nervous system injury
      decreased, while necrotizing enterocolitis-related deaths increased. (Funded by
      the National Institutes of Health.).

PMID- 25607432
TI  - A biologic Velcro patch.

PMID- 25607433
TI  - Rituximab or azathioprine maintenance in ANCA-associated vasculitis.

PMID- 25607434
TI  - Rituximab or azathioprine maintenance in ANCA-associated vasculitis.

PMID- 25607435
TI  - Rituximab or azathioprine maintenance in ANCA-associated vasculitis.

PMID- 25607436
TI  - Rituximab or azathioprine maintenance in ANCA-associated vasculitis.

PMID- 25607437
TI  - Cost-effectiveness of CT screening in the National Lung Screening Trial.

PMID- 25607438
TI  - Cost-effectiveness of CT screening in the National Lung Screening Trial.

PMID- 25607439
TI  - Cost-effectiveness of CT screening in the National Lung Screening Trial.

PMID- 25607440
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25607441
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25607442
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25607443
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25607444
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25607445
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25607446
TI  - Hidden formaldehyde in e-cigarette aerosols.

PMID- 25607448
TI  - Images in clinical medicine. Acute colonic pseudo-obstruction.

PMID- 25607449
TI  - Conflicting Readmission Rate Trends in a High-Risk Population: Implications for
      Performance Measurement.
AB  - The 30-day readmission rate is a common performance indicator for hospitals and
      accountable care entities. There is reason to question whether measuring
      readmissions as a function of hospital discharges is an appropriate measure of
      performance for initiatives that aim to improve overall cost and quality outcomes
      in a population. The objectives of this study were to compare trends in 30-day
      readmission rates per discharge to population-based measures of hospital
      admission and readmission frequency in a high-risk statewide Medicaid population
      over a 5-year period of quality improvement and care management intervention.
      Further, this study aimed to examine case-mix changes among hospitalized
      beneficiaries over time. This was a retrospective analysis of North Carolina
      Medicaid paid claims 2008 through 2012 for beneficiaries with multiple chronic or
      catastrophic conditions. Thirty-day readmission rates per discharge trended
      upward from 18.3% in 2008 to 18.7% in 2012. However, the rate of 30-day
      readmissions per 1000 beneficiaries declined from 123.3 to 110.7. Overall
      inpatient admissions per 1000 beneficiaries decreased from 579.4 to 518.5. The
      clinical complexity of hospitalized patients increased over the 5-year period.
      Although rates of hospital admissions and readmissions fell substantially in this
      high-risk population over 5 years, the 30-day readmission rate trend appeared
      unfavorable when measured as a percent of hospital discharges. This may be
      explained by more complex patients requiring hospitalization over time. The
      choice of metrics significantly affects the perceived effectiveness of
      improvement initiatives. Emphasis on readmission rates per discharge may be
      misguided for entities with a population health management focus.

PMID- 25607450
TI  - AMPK helps T cells survive nutrient starvation.
AB  - Reprogramming of cellular metabolism is crucial for T cells responding to
      environmental cues. Blagih et al. (2015) reveal that the kinase AMPK directs
      metabolic adaption of effector T cells upon nutrient limitation and contributes
      to immune responses in vivo.

PMID- 25607451
TI  - Taking T cell priming down a Notch: signaling through Notch receptors enhances T
      cell sensitivity to antigen.
AB  - Notch receptors are widely expressed and have recognized functions in thymocytes
      and mature T cells. In this issue, Laky et al. (2015) show that Notch
      interactions with Delta-like ligand 4 (DLL4) amplify priming of naive T cells.

PMID- 25607452
TI  - Self-determination in the T cell repertoire.
AB  - The number of T cells specific for various antigens can vary dramatically. In
      this issue of Immunity, Nelson et al. (2015) report that these differences might
      be, at least in part, set by the number of cross-reactive self peptides
      encountered by T cells during development.

PMID- 25607453
TI  - Monocytes compensate Kupffer cell loss during bacterial infection.
AB  - Liver Kupffer cells (KCs) are self-maintained tissue-resident macrophages. In
      this issue of Immunity, Bleriot et al. demonstrate that bacterial infection leads
      to KC necroptosis and quantitative replacement by monocyte-derived macrophages
      that contribute to antibacterial immunity and restoration of tissue integrity.

PMID- 25607454
TI  - Myeloid cells stimulate their progenitors in an emergency.
AB  - The nature and functions of cells creating hematopoietic niches during
      inflammation remain incompletely understood. In this issue of Immunity, Kwak et
      al. (2015) reveal that myeloid cell-produced reactive oxygen species stimulate
      proliferation of myeloid progenitors establishing an additional mechanism to
      regulate hematopoiesis.

PMID- 25607455
TI  - White, brown, and beige; type 2 immunity gets hot.
AB  - The biogenesis of beige fat is poorly understood. In recent issues of Nature and
      Cell, Brestoff et al. (2014) and Lee et al. (2015) demonstrate that resident
      innate lymphoid cells in subcutaneous fat generate and activate beige adipocytes,
      producing thermogenesis.

PMID- 25607456
TI  - Mouse genome engineering via CRISPR-Cas9 for study of immune function.
AB  - Clustered regularly interspaced palindromic repeats (CRISPR)-associated (Cas9)
      technology has proven a formidable addition to our armory of approaches for
      genomic editing. Derived from pathways in archaea and bacteria that mediate the
      resistance to exogenous genomic material, the CRISPR-Cas9 system utilizes a short
      single guide RNA (sgRNA) to direct the endonuclease Cas9 to virtually anywhere in
      the genome. Upon targeting, Cas9 generates DNA double-strand breaks (DSBs) and
      facilitates the repair or insertion of mutations, insertion of recombinase
      recognition sites, or large DNA elements. Here, we discuss the practical
      advantages of the CRISPR-Cas9 system over conventional and other nuclease-based
      targeting technologies and provide suggestions for the use of this technology to
      address immunological questions.

PMID- 25607457
TI  - Antimicrobial defense of the intestine.
AB  - The mammalian gastrointestinal tract is home to a dense community of resident
      bacteria and is also exposed to microorganisms from the external environment. The
      epithelial surface of the intestine plays a critical role in host protection by
      producing a diverse repertoire of antimicrobial proteins that directly kill or
      hinder the growth of microorganisms. Here we discuss the general principles that
      govern the mechanisms of action of epithelial antimicrobial proteins, regulation
      of antimicrobial protein expression and activity, and in vivo functions of
      intestinal antimicrobial proteins. We also consider how altered antimicrobial
      protein expression and function can contribute to disease and how these
      endogenous antibiotics might be harnessed for the benefit of human health.

PMID- 25607458
TI  - The energy sensor AMPK regulates T cell metabolic adaptation and effector
      responses in vivo.
AB  - Naive T cells undergo metabolic reprogramming to support the increased energetic
      and biosynthetic demands of effector T cell function. However, how nutrient
      availability influences T cell metabolism and function remains poorly understood.
      Here we report plasticity in effector T cell metabolism in response to changing
      nutrient availability. Activated T cells were found to possess a glucose
      sensitive metabolic checkpoint controlled by the energy sensor AMP-activated
      protein kinase (AMPK) that regulated mRNA translation and glutamine-dependent
      mitochondrial metabolism to maintain T cell bioenergetics and viability. T cells
      lacking AMPKalpha1 displayed reduced mitochondrial bioenergetics and cellular ATP
      in response to glucose limitation in vitro or pathogenic challenge in vivo.
      Finally, we demonstrated that AMPKalpha1 is essential for T helper 1 (Th1) and
      Th17 cell development and primary T cell responses to viral and bacterial
      infections in vivo. Our data highlight AMPK-dependent regulation of metabolic
      homeostasis as a key regulator of T cell-mediated adaptive immunity.

PMID- 25607459
TI  - A20 restricts ubiquitination of pro-interleukin-1beta protein complexes and
      suppresses NLRP3 inflammasome activity.
AB  - Inappropriate inflammasome activation contributes to multiple human diseases, but
      the mechanisms by which inflammasomes are suppressed are poorly understood. The
      NF-kappaB inhibitor A20 is a ubiquitin-modifying enzyme that might be critical in
      preventing human inflammatory diseases. Here, we report that A20-deficient
      macrophages, unlike normal cells, exhibit spontaneous NLRP3 inflammasome activity
      to LPS alone. The kinase RIPK3, but not the adaptor MyD88, is required for this
      response. In normal cells, A20 constitutively associates with caspase-1 and pro
      IL-1beta, and NLRP3 activation further promotes A20 recruitment to the
      inflammasome. Pro-IL-1beta also co-immunoprecipitates with RIPK1, RIPK3, caspase
      1, and caspase-8 in a complex that is modified with K63-linked and unanchored
      polyubiquitin. In A20-deficient macrophages, this pro-IL-1beta-associated
      ubiquitination is markedly increased in a RIPK3-dependent manner. Mass
      spectrometric and mutational analyses reveal that K133 of pro-IL-1beta is a
      physiological ubiquitination site that supports processing. Our study reveals a
      mechanism by which A20 prevents inflammatory diseases.

PMID- 25607460
TI  - Notch signaling regulates antigen sensitivity of naive CD4+ T cells by tuning co
      stimulation.
AB  - Adaptive immune responses begin when naive CD4(+) T cells engage peptide+major
      histocompatibility complex class II and co-stimulatory molecules on antigen
      presenting cells (APCs). Notch signaling can influence effector functions in
      differentiated CD4(+) T helper and T regulatory cells. Whether and how ligand
      induced Notch signaling influences the initial priming of CD4(+) T cells has not
      been addressed. We have found that Delta Like Ligand 4 (DLL4)-induced Notch
      signaling potentiates phosphatidylinositol 3-OH kinase (PI3K)-dependent signaling
      downstream of the T cell receptor+CD28, allowing naive CD4(+) T cells to respond
      to lower doses of antigen. In vitro, DLL4-deficient APCs were less efficient
      stimulators of CD4(+) T cell activation, metabolism, proliferation, and cytokine
      secretion. With deletion of DLL4 from CD11c(+) APCs in vivo, these deficits
      translated to an impaired ability to mount an effective CD4(+)-dependent anti
      tumor response. These data implicate Notch signaling as an important regulator of
      adaptive immune responses.

PMID- 25607462
TI  - Strategically localized dendritic cells promote rapid T cell responses to lymph
      borne particulate antigens.
AB  - Upon infection, adaptive immune responses play catch-up with rapidly replicating
      pathogens. While mechanisms for efficient humoral responses to lymph-borne
      antigens have been characterized, the current paradigm for T cell responses to
      infections and particulate vaccines involves delayed migration of peripheral
      antigen-bearing dendritic cells (DCs) to lymph nodes (LNs), where they elicit
      effector T cell responses. Utilizing whole LN 3D imaging, histo-cytometry, and
      intravital 2-photon microscopy, we have identified a specialized population of
      DCs, enriched in the LN-resident CD11b(+) subset, which resides within the
      lymphatic sinus endothelium and scans lymph with motile dendrites. These DCs
      capture draining particles and present associated antigens to T lymphocytes,
      inducing T cell responses much sooner than and independently of migratory DCs.
      Thus, strategic DC subset positioning in LNs limits a potentially costly delay in
      generation of T cell responses to lymph-borne antigens, contributing to effective
      host defense. These findings are also highly relevant to vaccine design.

PMID- 25607461
TI  - Individual T helper cells have a quantitative cytokine memory.
AB  - The probabilistic expression of cytokine genes in differentiated T helper (Th)
      cell populations remains ill defined. By single-cell analyses and mathematical
      modeling, we show that one stimulation featured stable cytokine nonproducers as
      well as stable producers with wide cell-to-cell variability in the magnitude of
      expression. Focusing on interferon-gamma (IFN-gamma) expression by Th1 cells,
      mathematical modeling predicted that this behavior reflected different cell
      intrinsic capacities and not mere gene-expression noise. In vivo, Th1 cells sort
      purified by secreted IFN-gamma amounts preserved a quantitative memory for both
      probability and magnitude of IFN-gamma re-expression for at least 1 month.
      Mechanistically, this memory resulted from quantitatively distinct transcription
      of individual alleles and was controlled by stable expression differences of the
      Th1 cell lineage-specifying transcription factor T-bet. Functionally, Th1 cells
      with graded IFN-gamma production competence differentially activated Salmonella
      infected macrophages for bacterial killing. Thus, individual Th cells commit to
      produce distinct amounts of a given cytokine, thereby generating functional
      intrapopulation heterogeneity.

PMID- 25607464
TI  - Pyrrolizidine Alkaloid Production of Jacobaea aquatica under Different Cutting
      Regimes.
AB  - Jacobaea aquatica (Asteraceae) growing in wet grasslands with low management
      intensity is regarded as a noxious weed with pyrrolizidine alkaloids (PAs), which
      cause health problems to livestock. The influence of different management
      practices on the production of PAs and on the proportion of J. aquatica in the
      fodder was studied. Five cutting regimes were applied during 4 years on permanent
      plots in lower Austria. The toxicity of the fodder was assessed by recording dry
      weight and alkaloid content of J. aquatica and total aboveground biomass.
      Different cutting regimes had significant effects on the PA content of J.
      aquatica and on its proportion in the fodder. The content of J. aquatica was
      lowest in fodder of June and October cuts and highest in second cuts in July and
      August. Total alkaloid contents exceeding 100 mg/kg were found in fodder
      harvested in July and August. After cutting, the toxic plants regenerated quickly
      and produced new flowering stalks within 4-5 weeks. Six macrocylic PAs were
      evaluated, with Z-erucifoline as the most abundant compound. The alkaloid levels
      were highest in plants cut during summer when flowering plants were present.
      Consequently, this fodder should not be fed to livestock over a long period of
      time.

PMID- 25607465
TI  - Shared timing variability in eye and finger movements increases with interval
      duration: Support for a distributed timing system below and above one second.
AB  - The origins of the ability to produce action at will at the hundreds of
      millisecond to second range remain poorly understood. A central issue is whether
      such timing is governed by one mechanism or by several different mechanisms,
      possibly invoked by different effectors used to perform the timing task. If two
      effectors invoke similar timing mechanisms, then they should both produce similar
      variability increase with interval duration (interonset interval) and thus adhere
      to Weber's law (increasing linearly with the duration of the interval to be
      timed). Additionally, if both effectors invoke the same timing mechanism, the
      variability of the effectors should be highly correlated across participants. To
      test these possibilities, we assessed the behavioural characteristics across
      fingers and eyes as effectors and compared the timing variability between and
      within them as a function of the interval to be produced (interresponse
      interval). Sixty participants produced isochronous intervals from 524 to 1431 ms
      with their fingers and their eyes. High correlations within each effector
      indicated consistent performance within participants. Consistent with a single
      mechanism, temporal variability in both fingers and eyes followed Weber's law,
      and significant correlations between eye and finger variability were found for
      several intervals. These results can support neither the single clock nor the
      multiple clock hypotheses but instead suggest a partially overlapping distributed
      timing system. 

PMID- 25607463
TI  - Enhancer sequence variants and transcription-factor deregulation synergize to
      construct pathogenic regulatory circuits in B-cell lymphoma.
AB  - Most B-cell lymphomas arise in the germinal center (GC), where humoral immune
      responses evolve from potentially oncogenic cycles of mutation, proliferation,
      and clonal selection. Although lymphoma gene expression diverges significantly
      from GC B cells, underlying mechanisms that alter the activities of corresponding
      regulatory elements (REs) remain elusive. Here we define the complete pathogenic
      circuitry of human follicular lymphoma (FL), which activates or decommissions REs
      from normal GC B cells and commandeers enhancers from other lineages. Moreover,
      independent sets of transcription factors, whose expression was deregulated in
      FL, targeted commandeered versus decommissioned REs. Our approach revealed two
      distinct subtypes of low-grade FL, whose pathogenic circuitries resembled GC B or
      activated B cells. FL-altered enhancers also were enriched for sequence variants,
      including somatic mutations, which disrupt transcription-factor binding and
      expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of
      FL reveals distinct genetic and epigenetic etiologies for GC B-cell
      transformation. 

PMID- 25607467
TI  - Using chromate to investigate the impact of natural organics on the surface
      reactivity of nanoparticulate magnetite.
AB  - Chromate was used as a chemical probe to investigate the size-dependent influence
      of organics on nanoparticle surface reactivity. Magnetite-chromate sorption
      experiments were conducted with ~ 90 and ~ 6 nm magnetite nanoparticles in the
      presence and absence of fulvic acid (FA), natural organic matter (NOM), and
      isolated landfill leachate (LL). Results indicated that low concentrations (1
      mg/L) of organics had no noticeable impact on chromate sorption, whereas
      concentrations of 50 mg/L or more resulted in decreased amounts of chromate
      sorption. The adsorption of organics onto the magnetite surfaces interfered
      equally with the ability of the 6 and 90 nm particles to sorb chromate from
      solution, despite the greater surface area of the smaller particles. Results
      indicate the presence of organics did not impact the redox chemistry of the
      magnetite-chromate system over the duration of the experiments (8 h), nor did the
      organics interact with the chromate in solution. Brunauer-Emmett-Teller (BET) and
      scanning electron microscopy (SEM) results indicate that the organics blocked the
      surface reactivity by occupying surface sites on the particles. The similarity of
      results with FA and NOM suggests that coverage of the reactive mineral surface is
      the main factor behind the inhibition of surface reactivity in the presence of
      organics.

PMID- 25607468
TI  - Palladium-catalyzed regioselective benzylation-annulation of pyridine N-oxides
      with toluene derivatives via multiple C-H bond activations: benzylation versus
      arylation.
AB  - A palladium-catalyzed cross-dehydrogenative coupling (CDC) reaction of pyridine N
      oxides with toluenes has been developed that operates under mild conditions. 2
      Benzylpyridines can be obtained directly by this method via a CDC reaction
      between unactivated toluenes and pyridine N-oxides. In addition, azafluorene N
      oxides, of value for future medicinal chemistry applications, can be obtained
      successfully by this procedure via four tandem C-H bond activations. 

PMID- 25607466
TI  - TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer.
AB  - Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian
      cancer, but drug resistance becomes a major limitation of its success clinically.
      The key molecule or mechanism associated with paclitaxel resistance in ovarian
      cancer still remains unclear. Here, we showed that TXNDC17 screened from 356
      differentially expressed proteins by LC-MS/MS label-free quantitative proteomics
      was more highly expressed in paclitaxel-resistant ovarian cancer cells and
      tissues, and the high expression of TXNDC17 was associated with poorer prognostic
      factors and exhibited shortened survival in 157 ovarian cancer patients.
      Moreover, paclitaxel exposure induced upregulation of TXNDC17 and BECN1
      expression, increase of autophagosome formation, and autophagic flux that
      conferred cytoprotection for ovarian cancer cells from paclitaxel. TXNDC17
      inhibition by siRNA or enforced overexpression by a pcDNA3.1(+)-TXNDC17 plasmid
      correspondingly decreased or increased the autophagy response and paclitaxel
      resistance. Additionally, the downregulation of BECN1 by siRNA attenuated the
      activation of autophagy and cytoprotection from paclitaxel induced by TXNDC17
      overexpression in ovarian cancer cells. Thus, our findings suggest that TXNDC17,
      through participation of BECN1, induces autophagy and consequently results in
      paclitaxel resistance in ovarian cancer. TXNDC17 may be a potential predictor or
      target in ovarian cancer therapeutics. 

PMID- 25607469
TI  - An assessment of surgical and anesthesia staff at 10 government hospitals in
      Sierra Leone.
AB  - IMPORTANCE: Strengthening workforce capacity to deliver essential surgical and
      anesthesia care has been identified as a strategy for addressing the unmet burden
      of morbidity and mortality in under-resourced countries. Sierra Leone is one of
      the poorest countries in the world and faces the challenge of stretching limited
      resources to provide appropriate health care for a population of 6 million.
      OBJECTIVES: To investigate the training of surgical and anesthesia staff in
      Sierra Leone and to build an evidence base for future health care policy and
      training programs tailored to local needs. DESIGN, SETTING, AND PARTICIPANTS:
      Health care professionals who conduct surgery or deliver anesthesia at 10 of the
      23 government hospitals in Sierra Leone were surveyed regarding training and
      clinical practices. This study surveyed 36 of 70 surgical staff (51%) and 38 of
      68 nurse specialists (56%) nationally. MAIN OUTCOMES AND MEASURES: Descriptive
      analysis of demographic details, training levels, and reported needs for future
      development. RESULTS: Thirty-six surgeons were surveyed in study hospitals, of
      whom the majority had limited surgical specialization training, whereas most
      anesthesia was provided by 47 nurse specialists. All consultants had postgraduate
      qualifications, but 4 of 6 medical superintendents (67%) and all medical officers
      lacked postgraduate surgical qualifications or formal surgical specialist
      training. The number of trained anesthesia staff increased after the introduction
      of the Nurse Anesthesia Training Program in 2008, funded by the United Nations
      Fund for Population Activities, increasing the number from 2 to 47 anesthesia
      staff based at the study hospitals. Although 32 of 37 nurse anesthetists (86%)
      reported having attended training workshops, 30 of 37 (>80%) described anesthesia
      resources as "poor," reporting a critical need for anesthesia machines and
      continual oxygen supply. Of the 37, 25 specifically mentioned the need for a
      better-functioning anesthesia machine and 16 mentioned the need for oxygen.
      CONCLUSIONS AND RELEVANCE: To address unmet surgical need in the long term,
      accredited local surgical specialization programs are required; training of
      nonphysician surgical practitioners may offer a short-term solution. To develop
      safe anesthesia care, governments and donors should focus on providing health
      care professionals with essential equipment and resources.

PMID- 25607470
TI  - Dermatology in an age of fully transparent electronic medical records.

PMID- 25607471
TI  - Recombinant human vascular endothelial growth factor receptor 1 effectively
      inhibits angiogenesis in vivo.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in both
      physiological and pathological angiogenesis. VEGF receptor-1 (VEGFR-1) acts as a
      decoy VEGF receptor that enables the regulation of VEGF on the vascular
      endothelium. In the present study, the recombinant human VEGFR1D1-3/Fc (rhVEGFR
      1), which contains key domains for VEGF binding, was cloned and expressed in
      Chinese hamster ovary (CHO) cells. The rhVEGFR-1 protein was purified using
      protein-A affinity chromatography. The molecular weight of rhVEGFR-1 was found to
      be ~162 and 81 kD in non-reducing and reducing SDS-PAGE, respectively. The
      majority of the final protein products were in the dimeric conformation. Western
      blot analysis revealed that rhVEGFR-1 was only capable of binding to the full
      glycan form of rhVEGF-165 and rhVEGF-121. The dissociation constant for the
      binding of rhVEGFR-1 to VEGF-165, detected using Biacore, was 285 pM. In
      addition, rhVEGFR-1 inhibited the proliferation and migration of human
      microvascular endothelial cells. In vivo experiments also demonstrated that
      rhVEGFR-1 inhibited chicken chorioallantoic membrane neovascularization and
      angiogenesis in nude mice. In conclusion, an anti-angiogenic recombinant soluble
      VEGFR was expressed (up to 5 mg/l) in CHO cells and was shown to be capable of
      inhibiting neovascularization in vivo and in vitro.

PMID- 25607472
TI  - Insulin-like growth factor-I and UVB photoprotection in human keratinocytes.
AB  - Ultraviolet radiation (UVR), in particular the UVB spectrum, is a risk factor for
      skin cancer development. The generation and accumulation of UVB-induced genetic
      mutations are fundamental premalignant events. Keratinocyte interactions between
      other cutaneous cell populations and the surrounding microenvironment determine
      cell fate and acute photoresponses. In this study, the importance of the insulin
      like growth factor (IGF) system, in particular the insulin-like growth factor-I
      (IGF-I), on influencing key processes in the keratinocyte acute photoresponse was
      investigated. Exogenous IGF-I and other growth factors present in dermal
      fibroblast-conditioned media (CM) were found to significantly enhance
      keratinocyte survival following UVB irradiation in vitro. This pretreatment was
      also shown to cause a shift in the expression levels of various DNA damage
      response proteins. Consequently, this was associated with accelerated rates of
      UVB-induced cyclobutane pyrimidine dimer removal in these samples. Finally,
      activation of the IGF system influenced cell cycle progression in UVB-irradiated
      keratinocytes. Taken together, these results highlight the importance of the IGF
      signalling network in initiating the repair of potentially mutagenic DNA damage
      in human keratinocytes. The dysregulation of these processes may therefore have
      significant implications in the aetiology of skin cancers and other cutaneous
      diseases. 

PMID- 25607473
TI  - Inhibition of microtubule-associated protein 1 light chain 3B via small
      interfering RNA or 3-methyladenine impairs hypoxia-induced HO8910PM and HO8910
      epithelial ovarian cancer cell migration and invasion and is associated with RhoA
      and alterations of the actin cytoskeleton.
AB  - Expression of microtubule-associated protein 1 light chain 3 (LC3) is correlated
      with poor prognosis in many human cancers. Hypoxia induces LC3 expression and is
      an essential characteristic of epithelial ovarian cancer (EOC). The aim of the
      present study was to elucidate the mechanism by which LC3 facilitates EOC cell
      migration and invasion under conditions of hypoxia. The effects of LC3B
      inhibition under hypoxic conditions on migration, invasion, and adhesion in
      HO8910PM and HO8910 EOC cell lines were investigated. LC3B inhibition was
      achieved by small-interfering RNA (siRNA) targeting LC3B or by treatment with 3
      methyladenine (3-MA). Cell migration, invasion and adhesion and the arrangement
      of the cytoskeleton were determined by Transwell migration assays and rhodamine
      phalloidin staining. Western blot analysis was performed to evaluate the
      expression level of LC3B and the expression and activity of ras homolog gene
      family member A (RhoA). Increased LC3B expression was associated with HO8910PM
      and HO8910 cell migration and invasion promoted under hypoxic conditions. LC3B
      siRNA and 3-MA treatment each attenuated hypoxia-induced LC3B expression, along
      with migration and invasion, and this was associated with a decrease in RhoA
      expression and disorganization of the actin cytoskeleton. LC3B may promote the
      migration and invasion of EOC cells by affecting the cytoskeleton via the RhoA
      pathway. In addition, LC3B may be a marker of tumor hypoxia and/or metastasis in
      EOC cells.

PMID- 25607474
TI  - BRAF wild-type melanoma in situ arising in a BRAF V600E mutant dysplastic nevus.
AB  - IMPORTANCE: The BRAF V600E mutation accounts for the majority of BRAF mutations
      found in cutaneous melanoma and is also commonly found in nevi. We used
      dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence
      analysis to highlight BRAF V600E heterogeneity within a multicomponent
      melanocytic proliferation. This sampling technique demonstrates the prospect of
      in vivo application in a clinical setting. OBSERVATIONS: A man in his 50s with
      Fitzpatrick skin type II presented with an irregularly pigmented melanocytic
      lesion on his back that met melanoma-specific dermoscopic criteria, and
      diagnostic shave excision of the lesion was performed. Histopathologic analysis
      revealed a melanoma in situ arising in a dysplastic nevus. Dermoscopy-targeted
      microbiopsy specimens were taken across the lesion, and genotyping was carried
      out on extracted DNA samples for BRAF and NRAS mutations. The melanoma in situ
      showed only BRAF wild-type results, while the dysplastic nevus showed both BRAF
      wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS
      wild-type genotype. CONCLUSIONS AND RELEVANCE: Dermoscopy-targeted sampling and
      genotyping of a melanoma in situ arising in a dysplastic nevus revealed a
      phenotype-genotype paradox that confounds the exclusive significance of BRAF and
      NRAS mutations in melanoma pathogenesis. Further studies are required to
      investigate the importance of other candidate genes linked to melanomagenesis.

PMID- 25607475
TI  - Kr/Kc but not dN/dS correlates positively with  body mass in birds, raising
      implications for  inferring lineage-specific selection.
AB  - BACKGROUND: The ratio of the rates of non-synonymous and synonymous substitution
      (dN/dS) is commonly used to estimate selection in coding sequences. It is often
      suggested that, all else being equal, dN/dS should be lower in populations with
      large effective size (Ne) due to increased efficacy of purifying selection. As Ne
      is difficult to measure directly, life history traits such as body mass, which is
      typically negatively associated with population size, have commonly been used as
      proxies in empirical tests of this hypothesis. However, evidence of whether the
      expected positive correlation between body mass and dN/dS is consistently
      observed is conflicting. RESULTS: Employing whole genome sequence data from 48
      avian species, we assess the relationship between rates of molecular evolution
      and life history in birds. We find a negative correlation between dN/dS and body
      mass, contrary to nearly neutral expectation. This raises the question whether
      the correlation might be a method artefact. We therefore in turn consider non
      stationary base composition, divergence time and saturation as possible
      explanations, but find no clear patterns. However, in striking contrast to dN/dS,
      the ratio of radical to conservative amino acid substitutions (Kr/Kc) correlates
      positively with body mass. CONCLUSIONS: Our results in principle accord with the
      notion that non-synonymous substitutions causing radical amino acid changes are
      more efficiently removed by selection in large populations, consistent with
      nearly neutral theory. These findings have implications for the use of dN/dS and
      suggest that caution is warranted when drawing conclusions about lineage-specific
      modes of protein evolution using this metric.

PMID- 25607476
TI  - Kinetic Analyses of Data from a Human Serum Albumin Assay Using the liSPR System.
AB  - We used the interaction between human serum albumin (HSA) and a high-affinity
      antibody to evaluate binding affinity measurements by the bench-top liSPR system
      (capitalis technology GmbH). HSA was immobilized directly onto a carboxylated
      sensor layer, and the mechanism of interaction between the antibody and HSA was
      investigated. The bivalence and heterogeneity of the antibody caused a complex
      binding mechanism. Three different interaction models (1:1 binding, heterogeneous
      analyte, bivalent analyte) were compared, and the bivalent analyte model best fit
      the curves obtained from the assay. This model describes the interaction of a
      bivalent analyte with one or two ligands (A + L <-> LA + L <-> LLA). The apparent
      binding affinity for this model measured 37 pM for the first reaction step, and
      20 pM for the second step. 

PMID- 25607477
TI  - Acute focal dystonic reaction after acute methylphenidate treatment in an
      adolescent patient.

PMID- 25607478
TI  - Low-power communication with a photonic heat pump.
AB  - An optical communication channel is constructed using a heated thermo
      electrically pumped, high efficiency infrared light-emitting diode (LED). In
      these devices, electro-luminescent cooling is observed, resulting in greater than
      unity (> 100%) efficiency in converting electrical power to optical power. The
      average amount of electrical energy required to generate a photon (4.3 meV) is
      much less than the optical energy in that photon (520 meV). Such a light source
      can serve as a test-bed for fundamental studies of energy-efficient bosonic
      communication channels. In this low energy consumption mode, we demonstrate data
      transmission at 3 kilobits per second (kbps) with only 120 picowatts of input
      electric power. Although the channel employs a mid-infrared source with limited
      quantum efficiency, a binary digit can be communicated using 40 femtojoules with
      a bit error rate of 3 x 10<sup>-3</sup>. 

PMID- 25607479
TI  - Energy efficiency and color quality limits in artificial light sources emulating
      natural illumination.
AB  - We present in this work a calculation of the theoretical limits attainable for
      natural light emulation with regard to the joint optimization of the Luminous
      Efficacy of Radiation and color fidelity by using multiple reflectance spectra
      datasets, along with an implementation of a physical device that approaches these
      limits. A reduced visible spectrum of blackbody radiators is introduced and
      demonstrated which allows lamps designed to emulate natural light to operate with
      excellent color fidelity and higher efficiency as compared to full visible
      spectrum sources. It is shown that even though 3,000K and 5,500K blackbody
      sources have maximum efficacies of 21 lm/W and 89 lm/W, respectively, reduced
      spectrum artificial light sources can exceed those values up to 363 lm/W and 313
      lm/W, respectively, while retaining excellent color fidelity. Experimental
      demonstration approaching these values is accomplished through the design and
      implementation of a 12-channel light engine which emits arbitrarily-tunable
      spectra. The color fidelity of the designed spectra is assessed through Color
      Rendering Maps, showing that color fidelity is preserved uniformly over a large
      spectral reflectance dataset, unlike other approaches to generate white light. 

PMID- 25607480
TI  - Enhanced performances in inverted small molecule solar cells by Ag nanoparticles.
AB  - We demonstrate a highly efficient inverted small molecular solar cell with
      integration of Ag nanoparticles (NPs) into the devices. The optimized device
      based on thermal evaporated Ag NPs provides a power conversion efficiency (PCE)
      of 4.87%, which offers 33% improvement than that of the reference device without
      Ag NPs. Such a high efficiency is mainly attributed to the improved electrical
      properties by virtue of the modification of the surface of ITO with Ag NPs and
      the enhanced light harvesting due to localized surface plasmon resonance (LSPR).
      The more detail enhanced mechanism of the PCE by introduction of Ag NPs is also
      discussed. 

PMID- 25607481
TI  - Improvement of the light extraction efficiency of GaN-based LEDs using rolled-up
      nanotube arrays.
AB  - In this paper, we have investigated the effect of rolled-up nanotubes on the
      light extraction efficiency of GaN-based LEDs using two-dimensional finite
      element method simulation. The light extraction involves two successive steps,
      including the coupling from the light source to the tube and the subsequent
      emission from the tube to the air. Significantly enhanced light extraction
      efficiency is observed for both TE and TM waves by optimizing the nanotube
      geometry and dimension as well as the separation between the nanotube and light
      source. We have further shown that densely packed nanotube arrays can be
      integrated with GaN-based LEDs to achieve unequivocal improvement of light
      extraction efficiency over a large surface area. With recent advances in rolled
      up micro- and nanotubes, it is expected that this study can offer a potentially
      flexible, low cost approach to enhance the light extraction of various LED
      devices. 

PMID- 25607482
TI  - Light outcoupling enhancement from top-emitting organic light-emitting diodes
      made on a nano-sized stochastic texture surface.
AB  - An effective method for enhancing the light outcoupling efficiency from top
      emitting organic light-emitting diodes (TEOLEDs) with a nano-sized stochastic
      texture surface (NSTS) is suggested. The broadly distributed pitch and the
      randomly sized of islands in the NSTS enable the photons that are otherwise
      trapped to be emitted over the broad emission wavelength range. The NSTS-embedded
      TEOLEDs have wide angular-dependent emission characteristics and an enhanced
      external quantum efficiency (EQE). Theoretical and full-wave optical calculations
      were performed to understand the mechanisms of the efficiency enhancement.
      Optimized TEOLEDs achieved a 32% EQE enhancement compared with the reference
      devices without the NSTS. 

PMID- 25607483
TI  - Light extraction enhancement of organic light-emitting diodes using aluminum zinc
      oxide embedded anodes.
AB  - Aluminum zinc oxide (AZO) has been embedded onto indium tin oxide (ITO) anode to
      enhance the light extraction from an organic light-emitting diode (OLED). The
      embedded AZO provides deflection and scattering interfaces on the newly generated
      AZO/organics and AZO/ITO interfaces rather than the conventional ITO/organic
      interface. The current efficiency of AZO embedded OLEDs was enhanced by up to
      64%, attributed to the improved light extraction by additionally created
      reflection and scattering of emitted light on the AZO/ITO interfaces which was
      roughed in AZO embedding process. The current efficiency was found to increase
      with the increasing AZO embedded area ratio, but limited by the accompanying
      increases in haze and electrical resistance of the AZO embedded ITO film. 

PMID- 25607484
TI  - MRGC performance evaluation model of gas leak infrared imaging detection system.
AB  - Gas leak infrared imaging detection technology has become one of the most
      effective means to detect gas leaks. We propose a novel MRGC (minimum resolvable
      gas concentration) model that is suitable for evaluating the performance of
      passive GLIIDSs (gas leak infrared imaging detection systems). An MRGC equivalent
      calculation method and a direct MRGC measurement method based on the MRTD
      (minimum resolvable temperature difference) model are also proposed. The MRGC
      measurement system is designed and built. The measured and calculated results are
      in good agreement, which verifies the MRGC model's correctness and demonstrates
      the effectiveness of the MRGC performance evaluation method. 

PMID- 25607485
TI  - Parallel LC circuit model for multi-band absorption and preliminary design of
      radiative cooling.
AB  - We perform a comprehensive analysis of multi-band absorption by exciting magnetic
      polaritons in the infrared region. According to the independent properties of the
      magnetic polaritons, we propose a parallel inductance and capacitance(PLC)
      circuit model to explain and predict the multi-band resonant absorption peaks,
      which is fully validated by using the multi-sized structure with identical
      dielectric spacing layer and the multilayer structure with the same strip width.
      More importantly, we present the application of the PLC circuit model to
      preliminarily design a radiative cooling structure realized by merging several
      close peaks together. This omnidirectional and polarization insensitive structure
      is a good candidate for radiative cooling application. 

PMID- 25607486
TI  - Wideband antireflective circular polarizer exhibiting a perfect dark state in
      organic light-emitting-diode display.
AB  - We proposed wideband antireflective circular polarizer for realizing a true black
      state in all viewing directions in organic light-emitting-diode displays (OLEDs).
      Present commercialized wideband circular polarizer consisted of a half wave and a
      quarter wave plates having the refractive index parameter (Nz) of 1.5 in both
      films exhibits light leakage in the oblique viewing directions, deteriorating
      image quality of a black state. We evaluated Nzs of both films and proposed a new
      wideband antireflective circular polarizer with a perfect dark state in all
      viewing directions with Nz = 0.5 in both plates, which will greatly improve image
      quality of OLEDs. 

PMID- 25607487
TI  - Analysis and demonstration of atmospheric methane monitoring by mid-infrared open
      path chirped laser dispersion spectroscopy.
AB  - Atmospheric methane concentration levels were detected using a custom built laser
      dispersion spectrometer in a long open-path beam configuration. The instrument is
      driven by a chirped distributed feedback mid-infrared quantum cascade laser
      centered at ~1283.46 cm<sup>-1</sup> and covers intense rotational-vibrational
      transitions from the fundamental nu<sub>4</sub> band of methane. A full forward
      model simulating molecular absorption and dispersion profiles, as well as
      instrumental noise, is demonstrated. The instrument's analytical model is
      validated and used for quantitative instrumental optimization. The temporal
      evolution of atmospheric methane mixing ratios is retrieved using a fitting
      algorithm based on the model. Full error propagation analysis on precision gives
      a normalized sensitivity of ~3 ppm.m.Hz<sup>-0.5</sup> for atmospheric methane. 

PMID- 25607488
TI  - Enhanced optical phase conjugation in nonlinear metamaterials.
AB  - Optical phase conjugation by degenerate four-wave mixing in nonlinear
      metamaterials is studied theoretically by solving the coupled wave equations
      using a generalized version of the invariant imbedding method. The phase
      conjugate reflectance and the lateral shift of the phase-conjugate reflected
      beams are calculated and their dependencies on the frequency, the polarization,
      the incident angle, the material properties and the structure are investigated in
      detail. It is found that the efficiency of phase conjugation can be significantly
      enhanced due to the enhancement of electromagnetic fields in various metamaterial
      structures. 

PMID- 25607489
TI  - Efficiency dip observed with InGaN-based multiple quantum well solar cells.
AB  - The dip of external quantum efficiency (EQE) is observed on In(0.15)Ga(0.85)N/GaN
      multiple quantum well (MQW) solar cells upon the increase of incident optical
      power density. With indium composition increased to 25%, the EQE dip becomes much
      less noticeable. The composition dependence of EQE dip is ascribed to the
      competition between radiative recombination and photocurrent generation in the
      active region, which are dictated by quantum-confined Stark effect (QCSE) and
      composition fluctuation in the MQWs.

PMID- 25607490
TI  - Design of MUc-Si:H/a-Si:H coaxial tandem single-nanowire solar cells considering
      photocurrent matching.
AB  - The single nanowire solar cells (SNSCs) with radial junctions are expected to
      show the superiority in efficient carrier collection benefited from the largely
      shortened junction length. Considering that the conversion efficiency of the
      existing SNSCs is still limited due to the low operation voltage, we design MUc
      Si:H(core)/a-Si:H(shell) radial tandem SNSCs, giving much attention to the
      intrinsic optical and electrical properties. The core and shell cells are
      carefully engineered in order to realize the photocurrent matching. It is found
      that under matching condition the radius of the entire cell (R) shows linear
      dependence on the radius of the core cell (r), i.e., R ~1.2r. Under an optimal
      design of the tandem cell, the open-circuit voltage (photoconversion efficiency)
      is increased by 160% (34% relative) compared to the equivalent-size MUc-Si:H
      SNSCs. 

PMID- 25607491
TI  - Color-tunable, phosphor-free InGaN nanowire light-emitting diode arrays
      monolithically integrated on silicon.
AB  - We demonstrate controllable and tunable full color light generation through the
      monolithic integration of blue, green/yellow, and orange/red InGaN nanowire light
      emitting diodes (LEDs). Such multi-color nanowire LED arrays are fabricated
      directly on Si substrate using a three-step selective area molecular beam epitaxy
      growth process. The lateral-arranged multi-color subpixels enable controlled
      light mixing at the chip-level and yield color-tunable light emission with CCT
      values in the range from 1900 K to 6800 K, while maintaining excellent color
      rendering capability. This work provides a viable approach for achieving micron
      and nanoscale tunable full-color LED arrays without the compromise between the
      device efficiency and light quality associated with conventional phosphor-based
      LEDs. 

PMID- 25607492
TI  - Surface-plasmon-enhanced microcavity organic light-emitting diodes.
AB  - Efficiency enhancement of organic light-emitting diodes (OLEDs) can be obtained
      by the combination of microcavity effect and Au nanoparticles based surface
      plasmons. Au nanoparticles are thermally deposited on distributed Bragg reflector
      (DBR)-coated glass substrate, leading to realization of microcavity effect and
      localized surface plasmon effect. Our results show the current efficiency of
      OLEDs with DBR/Au nanoparticles as anode is increased by 72% compared to that
      with ITO as anode. 

PMID- 25607493
TI  - Light extraction analysis and enhancement in a quantum dot light emitting diode.
AB  - We apply a rigorous dipole model to analyze the light outcoupling and angular
      performance of quantum dot light emitting diode (QLED). To illustrate the design
      principles, we use a red QLED as an example and compare its performance with an
      organic light emitting diode (OLED). By combining a high refractive index glass
      substrate with macroextractors, our simulation results indicate that the light
      outcoupling efficiency is doubled from ~40% to ~80%. After analyzing the light
      emission spectra and angular radiation pattern of the device, we confirm that
      QLED has a much weaker color shift than OLED. 

PMID- 25607494
TI  - Regularly patterned non-polar InGaN/GaN quantum-well nanorod light-emitting diode
      array.
AB  - The growth and process of a regularly patterned nanorod (NR)- light-emitting
      diode (LED) array with its emission from sidewall non-polar quantum wells (QWs)
      are demonstrated. A pyramidal un-doped GaN structure is intentionally formed at
      the NR top for minimizing the current flow through this portion of the NR such
      that the injection current can be effectively guided to the sidewall m-plane
      InGaN/GaN QWs for emission excitation by a conformal transparent conductor
      (GaZnO). The injected current density at a given applied voltage of the NR LED
      device is similar to that of a planar c-plane or m-plane LED. The blue-shift
      trend of NR LED output spectrum with increasing injection current is caused by
      the non-uniform distributions of QW width and indium content along the height on
      a sidewall. The photoluminescence spectral shift under reversed bias confirms
      that the emission of the fabricated NR LED comes from non-polar QWs. 

PMID- 25607495
TI  - Trace aerosol detection and identification by dynamic photoacoustic spectroscopy.
AB  - Dynamic photoacoustic spectroscopy (DPAS) is a high sensitivity technique for
      standoff detection of trace vapors. A field-portable DPAS system has potential as
      an early warning provider for gaseous-based chemical threats. For the first time,
      we utilize DPAS to successfully detect the presence of trace aerosols. Aerosol
      identification via long-wavelength infrared (LWIR) spectra is demonstrated. We
      estimate the sensitivity of our DPAS system to aerosols comprised of silica
      particles is comparable to that of SF(6) gas based on a signal level per
      absorbance unit metric for the two materials. The implications of these
      measurements are discussed.

PMID- 25607496
TI  - Planar solar concentrator featuring alignment-free total-internal-reflection
      collectors and an innovative compound tracker.
AB  - This study proposed a planar solar concentrator featuring alignment-free total
      internal-reflection (TIR) collectors and an innovative compound tracker. The
      compound tracker, combining a mechanical single-axis tracker and scrollable prism
      sheets, can achieve a performance on a par with dual-axis tracking while reducing
      the cost of the tracking system and increasing its robustness. The alignment-free
      TIR collectors are assembled on the waveguide without requiring alignment, so the
      planar concentrator is relatively easily manufactured and markedly increases the
      feasibility for use in large concentrators. Further, the identical TIR collector
      is applicable to various-sized waveguide slab without requiring modification,
      which facilitates flexibility regarding the size of the waveguide slab. In the
      simulation model, the thickness of the slab was 2 mm, and its maximal length
      reached 6 m. With an average angular tolerance of +/-0.6 degrees , and after
      considering both the Fresnel loss and the angular spread of the sun, the
      simulation indicates that the waveguide concentrator of a 1000-mm length provides
      the optical efficiencies of 62-77% at the irradiance concentrations of 387-688,
      and the one of a 2000-mm length provides the optical efficiencies of 52-64.5% at
      the irradiance concentrations of 645-1148. Alternatively, if a 100-mm
      horizontally staggered waveguide slab is collocated with the alignment-free TIR
      collectors, the optical efficiency would be greatly improved up to 91.5% at an
      irradiance concentration of 1098 (C(geo) = 1200X).

PMID- 25607497
TI  - Roll-to-roll embossing of optical linear Fresnel lens polymer film for solar
      concentration.
AB  - Roll-to-roll manufacturing has been proven to be a high-throughput and low-cost
      technology for continuous fabrication of functional optical polymer films. In
      this paper, we have firstly studied a complete manufacturing cycle of linear
      Fresnel lens polymer film for solar concentration in the aspects of ultra
      precision diamond machining of metal roller mold, roll-to-roll embossing, and
      measurement on film profile and functionality. A metal roller mold patterned with
      linear Fresnel lenses is obtained using single point diamond turning technique.
      The roller mold is installed onto a self-developed roll-to-roll UV embossing
      system to realize continuous manufacturing of linear Fresnel lens film. Profile
      measurement of the machined roller mold and the embossed polymer film, which is
      conducted using a stylus profilometer, shows good agreement between measured
      facet angles with designed ones. Functionality test is conducted on a solar
      simulation system with a reference solar cell, and results show that strong light
      concentration is realized. 

PMID- 25607498
TI  - High efficiency of photon-to-heat conversion with a 6-layered metal/dielectric
      film structure in the 250-1200 nm wavelength region.
AB  - The optical properties and thermal stability of a 6-layered metal/dielectric film
      structure are investigated in this work. A high optical absorption average of >
      98% is achieved in the broad spectral range of 250-1200 nm with experiment
      results, in good agreement with our simulated results. The samples have a typical
      layered structure of: SiO(2)(57.3 nm)/Ti(5.7 nm)/SiO(2) (67.1 nm)/Ti(11.6
      nm)/SiO(2)(51.4 nm)/Cu(>100 nm), deposited on optically polished Si or K9-glass
      substrates by magnetron sputtering. The sample of the 6-layered metal/dielectric
      film structure has an AM1.5G solar absorptance of 95.5% with the features of low
      thermal emittance of 0.136 at 700K and good thermal stability, and will be
      potentially suitable for practical application in high-efficiency solar absorber
      devices in many fields.

PMID- 25607499
TI  - Photoelectrochemical hydrogen generation with linear gradient Al composition
      dodecagon faceted AlGaN/n-GaN electrode.
AB  - We demonstrated photoelectrochemical cells (PECs) with dodecagon faceted AlGaN/n
      GaN heterostructure electrode for H(2) generation, where the AlGaN/n-GaN
      heterostructure has a linear gradient Al composition (LGAC). The separation
      efficiency of the photo-generated electron-hole pairs in the electrode performs a
      key function in the H(2) generation efficiency of PEC cells. The linear gradient
      Al composition, AlGaN, could create more internal field and light absorption
      because of the linear graded band gap. Therefore, the zero-bias photocurrent
      density of PEC cells with dodecagon facet LGAC AlGaN/n-GaN heterostructure
      electrode is around 5.9 times larger than that of dodecagon faceted n-GaN
      electrode.

PMID- 25607500
TI  - P-side-up thin-film AlGaInP-based light emitting diodes with direct ohmic contact
      of an ITO layer with a GaP window layer.
AB  - A twice wafer-transfer technique can be used to fabricate high-brightness p-side
      up thin-film AlGaInP-based light-emitting diodes (LEDs) with an indium-tin oxide
      (ITO) transparent conductive layer directly deposited on a GaP window layer,
      without using postannealing. The ITO layer can be used to improve light
      extraction, which enhances light output power. The p-side-up thin-film AlGaInP
      LED with an ITO layer exhibited excellent performance stability (e.g., emission
      wavelength and output power) as the injection current increased. This stability
      can be attributed to the following factors: 1) Refractive index matching,
      performed by introducing ITO between the epoxy and the GaP window layer enhances
      light extraction; and 2) The ITO layer is used as the current spreading layer to
      reduce the thermal accumulation in the epilayers. 

PMID- 25607501
TI  - Thermoresponsive scattering coating for smart white LEDs.
AB  - White light emitting diode (LED) systems, capable of lowering the color
      temperature of emitted light on dimming, have been reported in the literature.
      These systems all use multiple color LEDs and complex control circuitry. Here we
      present a novel responsive lighting system based on a single white light emitting
      LED and a thermoresponsive scattering coating. The coated LED automatically emits
      light of lower correlated color temperature (CCT) when the power is reduced. We
      also present results on the use of multiple phosphors in the white light LED
      allowing for the emission of warm white light in the range between 2900 K and
      4150 K, and with a chromaticity complying with the ANSI standards (C78.377). This
      responsive warm white light LED-system with close-to-ideal emission
      characteristics is highly interesting for the lighting industry. 

PMID- 25607502
TI  - Self-tracking solar concentrator with an acceptance angle of 32 degrees .
AB  - Solar concentration has the potential to decrease the cost associated with solar
      cells by replacing the receiving surface aperture with cheaper optics that
      concentrate light onto a smaller cell aperture. However a mechanical tracker has
      to be added to the system to keep the concentrated light on the size reduced
      solar cell at all times. The tracking device itself uses energy to follow the
      sun's position during the day. We have previously shown a mechanism for self
      tracking that works by making use of the infrared energy of the solar spectrum,
      to activate a phase change material. In this paper, we show an implementation of
      a working 53 x 53 mm(2) self-tracking system with an acceptance angle of 32
      degrees  ( +/- 16 degrees ). This paper describes the design optimizations and
      upscaling process to extend the proof-of-principle self-tracking mechanism to a
      working demonstration device including the incorporation of custom photodiodes
      for system characterization. The current version demonstrates an effective
      concentration of 3.5x (compared to 8x theoretical) over 80% of the desired
      acceptance angle. Further improvements are expected to increase the efficiency of
      the system and open the possibility to expand the device to concentrations as
      high as 200x (C(geo) = 400x, eta = 50%, for a solar cell matched spectrum).

PMID- 25607503
TI  - Superlattice photonic crystal as broadband solar absorber for high temperature
      operation.
AB  - A high performance solar absorber using a 2D tantalum superlattice photonic
      crystal (PhC) is proposed and its design is optimized for high-temperature energy
      conversion. In contrast to the simple lattice PhC, which is limited by
      diffraction in the short wavelength range, the superlattice PhC achieves solar
      absorption over broadband spectral range due to the contribution from two
      superposed lattices with different cavity radii. The superlattice PhC geometry is
      tailored to achieve maximum thermal transfer efficiency for a low concentration
      system of 250 suns at 1500 K reaching 85.0% solar absorptivity. In the high
      concentration case of 1000 suns, the superlattice PhC absorber achieves a solar
      absorptivity of 96.2% and a thermal transfer efficiency of 82.9% at 1500 K,
      amounting to an improvement of 10% and 5%, respectively, versus the simple square
      lattice PhC absorber. In addition, the performance of the superlattice PhC
      absorber is studied in a solar thermophotovoltaic system which is optimized to
      minimize absorber re-emission by reducing the absorber-to-emitter area ratio and
      using a highly reflective silver aperture. 

PMID- 25607504
TI  - Numerical method for an analysis of nonlinear light propagation in
      photorefractive media--time nonlocal approach.
AB  - Nonlinear light propagation in photorefractive media can be analyzed by numerical
      methods. The presented numerical approach has regard to the effects of time
      nonlocality. Two algorithms are presented, and compared in terms of physical
      results and computing times. The possibility to address the issue of time
      nonlocality in two ways is attributed to the fact that, it is possible to
      completely separate carrier dynamics evaluation and wave equation calculation.
      This in turn, allows to choose a short integration time for carrier dynamics and
      a longer one to solve the wave equation. The tests of the methods were carried
      out for a one-carrier model that describes most of photorefractive media, and for
      a model with bipolar transport and hot electron effect, used in descriptions of
      semiconductor materials. 

PMID- 25607505
TI  - Design of efficient LED optics with two free-form surfaces.
AB  - Most LED illumination applications require generation of complex light patterns
      for which the secondary optics with two free-form surfaces needs to be used. We
      present a novel optimization method for computing such type of optical elements.
      An analytical solution for the generation of the initial surfaces is proposed. To
      accelerate the optimization process, a specific surface representation is used,
      that eliminates the need to run a time-expensive raytracing procedure. As an
      example, an optical element generating uniformly illuminated rectangular area
      with size of 60 degrees  by 40 degrees  is computed. Lighting efficacy for the
      extended Lambertian source 1x1 mm is 88.5% and nonuniformity is less than 8.5%. 

PMID- 25607506
TI  - Structural study and Raman scattering analysis of Cu2ZnSiTe4 bulk crystals.
AB  - Bulk crystals of Cu(2)ZnSiTe(4) (CZSiTe) have been prepared by modified Bridgman
      method and have been investigated by single crystal X-ray method, Energy
      Dispersive X-Ray analysis and Raman scattering techniques. The structural studies
      revealed that the CZSiTe compounds crystallizes in the tetragonal space group I4
      2m, with a = b = 5.9612(1) A and c = 11.7887(4) A at 293 K. The Raman spectrum
      characteristic of the crystals exhibits nine peaks, with two dominant peaks at
      approximately 134 cm(-1) and 151 cm(-1) that can be used as fingerprint peaks for
      the identification of this compound. The Raman peaks were analyzed on the basis
      of the derived irreducible representation for the zone center phonons and by
      comparison with experimental and theoretical data from close related
      semiconductors as Cu(2)FeSnS(4) and Cu(2)ZnSnSe(4).

PMID- 25607507
TI  - Palliative care health professionals' experiences of caring for patients with
      advance care directives.
AB  - OBJECTIVE: To explore the health professionals' (HPs) perceptions and experiences
      of advance care directives (ACDs) and advance care planning in Australian
      palliative care services. METHODS: A nationwide survey of 105 palliative care
      services was conducted, with two HPs from each service invited to participate. A
      qualitative analysis of open responses about advance care planning was
      undertaken. RESULTS: Sixty questionnaires were returned with open responses. Most
      responders were nurses (75%), aged >=40 years (80%) and with a mean of 12 years
      palliative care experience. Data were grouped into four key themes: (1) the ACD;
      (2) the process of developing ACDs; (3) the process of using ACDs; and (4) the
      consequences of having ACDs. Participants were positive about advance care
      planning, commenting that ongoing communication about end-of-life care ensures
      mutual understanding between patients, family and HPs. Provision of care was
      considered easier and more efficient with an ACD in place. ACDs were perceived to
      reduce distrust and conflict between family, friends and HPs, and promote
      communication. Suboptimal documentation, clarity and explicitness limited the
      usefulness of ACDs when they were available. CONCLUSIONS: Advance care planning
      benefits HPs, patients and their family. To maximise these benefits, ACDs need to
      be clear, comprehensive, medically relevant and transportable documents.

PMID- 25607508
TI  - Catalytic transformation of aliphatic alcohols to corresponding esters in O2
      under neutral conditions using visible-light irradiation.
AB  - Selective oxidation of aliphatic alcohols under mild and base-free conditions is
      a challenging process for organic synthesis. Herein, we report a one-pot process
      for the direct oxidative esterification of aliphatic alcohols that is
      significantly enhanced by visible-light irradiation at ambient temperatures. The
      new methodology uses heterogenerous photocatalysts of gold-palladium alloy
      nanoparticles on a phosphate-modified hydrotalcite support and molecular oxygen
      as a benign oxidant. The alloy photocatalysts can absorb incident light, and the
      light-excited metal electrons on the surface of metal nanoparticles can activate
      the adsorbed reactant molecules. Tuning the light intensity and wavelength of the
      irradiation can remarkably change the reaction activity. Shorter wavelength light
      (<550 nm) drives the reaction more efficiently than light of longer wavelength
      (e.g., 620 nm), especially at low temperatures. The phosphate-exchanged
      hydrotalcite support provides sufficient basicity (and buffer) for the catalytic
      reactions; thus, the addition of base is not required. The photocatalysts are
      efficient and readily recyclable. The findings reveal the first example of using
      "green" oxidants and light energy to drive direct oxidative esterification of
      aliphatic alcohols under base-free, mild conditions. 

PMID- 25607509
TI  - Decreased vascular endothelial growth factor expression is associated with cell
      apoptosis in low-dose aspirin-induced gastric mucosal injury.
AB  - BACKGROUND: The use of low-dose aspirin (LDA) has emerged as an important cause
      of gastrointestinal ulcers. The aim of this study was to investigate the
      association between LDA-induced gastric mucosal injury and the expression of
      vascular endothelial growth factor (VEGF) and cell apoptosis in elderly Chinese
      patients. METHODS: A total of 136 patients aged 60 to 80 years with LDA-induced
      (100 mg/d for at least 1 month) gastric mucosal injury and 48 age-matched healthy
      subjects were enrolled in this study. The patients were divided into a low
      severity group and a high-severity group based on their modified Lanza scale
      scores. Biopsy specimens of gastric mucosa from all participants were subjected
      to immunohistochemical staining for VEGF expression and terminal deoxynucleotidyl
      transferase dUTP nick end labeling staining for cell apoptosis. Staining indices
      and apoptotic indices were applied to assess VEGF expression level and the extent
      of cell apoptosis. RESULTS: VEGF expression decreased significantly in the 2
      patient groups, whereas the extent of cell apoptosis significantly increased
      compared with the control group. Furthermore, Spearman's correlation coefficients
      suggest that VEGF expression levels and the extent of cell apoptosis in gastric
      mucosae shared a significant correlation with the severity of LDA-induced gastric
      mucosal injury. Receiver operating characteristics analysis further confirmed
      these results. CONCLUSIONS: Our findings provide important clues as to the
      underlying molecular mechanism behind gastric mucosal injury resulting from
      exposure to LDA in elderly adults, and also suggest that interventions
      specifically targeting the pathways associated with angiogenesis and apoptosis
      may help facilitate the healing process.

PMID- 25607510
TI  - Echinocandin use in hospitalized patients: a multi-institutional study.
AB  - BACKGROUND: The echinocandin antifungals are recommended as initial therapy in
      hospitalized patients with candidemia. Contemporary usage rates and indication
      for use of echinocandins have not been studied in the United States. The purpose
      of this study was to evaluate echinocandin usage patterns in community and
      academic teaching hospitals over time and to evaluate dose, duration of therapy
      and indications for use. METHODS: This study used hospital pharmacy databases
      from academic and community hospitals to collect information on adult inpatients
      given systemic antifungal agents from 2008 to 2012. Patient medical information
      was also obtained from randomly selected patients given an echinocandin over the
      same time period. RESULTS: Echinocandin use was determined for 4 academic and 34
      community hospitals. A significant increase in echinocandin use was observed in
      academic and community hospitals during the time period (P < 0.001). Two hundred
      forty-two randomly selected patients receiving an echinocandin were
      retrospectively reviewed. Indications for echinocandin use did not change during
      the time period and included empiric therapy in a high-risk patient without
      subsequent mycologic confirmation from a normally sterile site (55%), systemic
      candidiasis (43%) and prophylactic (2%). Fifty-six percent of patients had at
      least 1 anatomic site of mycologic growth; most commonly urine only (14%),
      respiratory only (12%) or blood only (7%). In patients with candidemia, the
      hospital treatment course with an echinocandin averaged 8.4 +/- 7.9 days (range,
      1-35 days). CONCLUSIONS: This study provides useful benchmark data on antifungal
      use and indications for use that could be used for antifungal stewardship program
      comparisons.

PMID- 25607511
TI  - An underdiagnosed ailment: scurvy in a tertiary care academic center.

PMID- 25607512
TI  - Complicated appendicitis with unusual complication: appendicovesical fistula.

PMID- 25607513
TI  - Vanishing lung syndrome of uncommon size.

PMID- 25607514
TI  - Prediction of renal outcomes in patients with crescentic lupus nephritis.
AB  - BACKGROUND: Few studies are currently available about the renal survival and risk
      factors of crescentic lupus nephritis (cLN). We retrospectively analyzed data
      from Chinese patients with cLN in our center to identify the prognostic factors.
      METHODS: One hundred twenty-four cases of biopsy-proven LN with >=50% crescents
      (cLN) were included in this study. Another 100 patients with LN without crescents
      were randomly enrolled as a control group. Their clinicopathological data and
      long-term outcome were compared. RESULTS: There were 101 females and 23 males
      with an average age of 32.0 +/- 13.5 years followed for a median period of 4
      years. At biopsy, the mean SCr level was 2.4 +/- 2.0 mg/dL, and the mean
      percentage of crescents was 64.4 +/- 13.3%. The renal survival rates at years 1,
      3 and 5 after biopsy of cLN group and the control group were 82.3% versus 97.8%,
      78.4% versus 92.6% and 70.2% versus 84.9%, respectively. Multivariate Cox
      regression revealed initial SCr concentration as the only independent risk factor
      for end-stage renal disease (hazard ratio: 1.433, P < 0.001). Logistic regression
      showed that the risk of end-stage renal disease at 5 years after biopsy increased
      rapidly at SCr >1.4 mg/dL and reached 90% at SCr >5.5 mg/dL. CONCLUSIONS:
      Crescentic LN had worse treatment response and lower probability of renal
      survival than those without crescents. Initial SCr concentration may predict
      kidney failure in patients with crescentic disease.

PMID- 25607515
TI  - Pulmonary function parameters in high-resolution computed tomography phenotypes
      of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Heterogeneity of clinical presentation of chronic obstructive
      pulmonary disease (COPD) attributes to different pathological basis. High
      resolution computed tomography (HRCT) phenotypes of COPD may reflex the
      pathological basis of COPD indirectly by evaluating the small airway inflammation
      and emphysema. How the pulmonary function related with different HRCT phenotypes
      has not been well known. The aim was to explore the features of pulmonary
      function parameters in the 3 phenotypes. METHODS: Sixty-three stable COPD
      patients were allocated in 3 groups based on HRCT findings: phenotype A (absence
      of emphysema, with minimal evidence of emphysema with or without bronchial wall
      thickening [BWT]), phenotype E (emphysema without BWT) and phenotype M (emphysema
      with BWT). The pulmonary function testing was also analyzed. RESULTS: The values
      of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC%),
      FEV1% and maximum expiratory flows (MEF)50% were the highest in phenotype A (P <
      0.05), so was residual volume (RV)/total lung capacity (TLC%) in phenotype E (P <
      0.05). Those with MEF50/MEF25 ratio >4.0 were more prevalence in phenotype A than
      in E and M (odds ratio = 2.214; P < 0.05). The occurrences of RV/TLC% >40% were
      higher in phenotype E than in A and M (odds ratio = 3.906; P < 0.05). Receiver
      operating characteristic analysis showed that the cutoff value of MEF50/MEF25
      ratio for identifying phenotype A was 2.5, with sensitivity 66.7% and specificity
      92.9%. The cutoff value of RV/TLC% for identifying phenotype E was 57.4%, with
      sensitivity 75.0% and specificity 79.1%. CONCLUSIONS: The different features of
      pulmonary function parameters were found in various HRCT phenotypes; MEF50/MEF25
      ratio could imply phenotype A, whereas RV/TLC% may be the indicator of phenotype
      E.

PMID- 25607516
TI  - Emperipolesis.

PMID- 25607518
TI  - Importance of peak height velocity timing in terms of injuries in talented soccer
      players.
AB  - The purpose of this study was to identify differences in traumatic and overuse
      injury incidence between talented soccer players who differ in the timing of
      their adolescent growth spurt. 26 soccer players (mean age 11.9 +/- 0.84 years)
      were followed longitudinally for 3 years around Peak Height Velocity, calculated
      according to the Maturity Offset Protocol. The group was divided into an earlier
      and later maturing group by median split. Injuries were registered following the
      FIFA consensus statement. Mann-Whitney tests showed that later maturing players
      had a significantly higher overuse injury incidence than their earlier maturing
      counterparts both in the year before Peak Height Velocity (3.53 vs.0.49 overuse
      injuries/1 000 h of exposure,U = 49.50, z = - 2.049, p < 0.05) and the year of
      Peak Height Velocity (3.97 vs. 1.56 overuse injuries/1 000 h of exposure, U =
      50.5, z = - 1.796,p < 0.05). Trainers and coaches should be careful with the
      training and match load they put on talented soccer players, especially those
      physically not (yet) able to handle that load. Players appear to be especially
      susceptible to injury between 13.5 and 14.5 years of age. Training and match load
      should be structured relative to maturity such that athletic development is
      maximized and the risk of injury is minimized.

PMID- 25607517
TI  - Use of Noncadaveric Human Acellular Dermal Tissue (BellaDerm) in Lower Eyelid
      Retraction Repair.
AB  - PURPOSE: To evaluate the efficacy and longevity of a human-derived, noncadaveric,
      acellular dermal implant (BellaDerm) as a posterior spacer graft in the
      correction of lower eyelid retraction, taking into consideration issues
      associated with the use of acellular dermis such as contraction and potential
      regression of repairs. METHODS: A prospective, nonrandomized clinical study
      involving the use of BellaDerm as a posterior spacer graft to correct symptomatic
      lower eyelid retraction secondary to involutional, cicatricial, and paralytic
      etiologies. Pre- and postoperative margin reflex distance 2 and inferior scleral
      show (ISS) were measured for each eyelid, and success was defined as a positive
      eyelid elevation and decrease in ISS. Long-term stability beyond 12 months was
      evaluated. Resolution of symptoms and postoperative complications were also
      documented. RESULTS: Fifteen eyelids of 11 patients were included. All eyes
      showed an improvement in eyelid elevation and decrease in ISS, both of which were
      statistically significant. The mean improvement in margin reflex distance 2 for
      all eyelids was 2.2 mm (p<0.0001). The mean decrease in ISS for all eyelids was
      1.7 mm (p<0.0001). The average duration of follow up was 15.6 months. Ten eyelids
      of seven patients had greater than 12 months of follow up (mean 21.9 months), and
      this subset was evaluated separately to emphasize longevity of results. In this
      subset, the mean improvement in margin reflex distance 2 was 2.4 mm (p<0.0001),
      and the mean decrease in ISS was 1.7 mm (p=0.0003). CONCLUSIONS: Noncadaveric
      human acellular dermal tissue is efficacious in treating lower eyelid retraction.
      BellaDerm produced long-term symptomatic relief and stable clinical correction of
      lower eyelid retraction secondary to multiple etiologies. These findings
      contradict the thinking that although acellular dermis is an adequate modality
      for correction of eyelid retraction, results may be compromised by graft
      resorption and recurrence of symptoms. Improved biological integrity from live
      donor harvesting or alternate processing techniques may contribute to the success
      of this particular acellular dermis.

PMID- 25607519
TI  - Does combined antioxidant vitamin supplementation blunt repeated bout effect?
AB  - We investigated the effect of antioxidant supplementation on markers of muscle
      damage, antioxidant status, and delayed onset of muscle soreness (DOMS) after
      repeated downhill runs. Moderately-trained males (n=22) were randomly assigned to
      a supplement (S) or placebo (P) group. Capsules (vitamin C:1 000 mg/d; vitamin E:
      400 IU/d) were ingested daily for 2 weeks. before the first (1D) and second (2D)
      downhill runs, and for 2 additional days following each run. Creatine kinase (CK)
      activity and oxygen radical absorbance capacity (ORAC) were measured pre-exercise
      and at 0 (immediately), 6, 24 and 48 h post-exercise (POST). DOMS was rated for
      quadriceps, hamstring, gluteus, gastrocnemius, and tibialis anterior at 0, 24, 48
      and 72 h POST. CK at 48 h following 1D remained elevated above pre-exercise only
      in P (P<0.01). Overall, DOMS of the quadriceps was lower in S (1.1+/-0.3) than P
      (2.2+/-0.5) (P<0.05). At 24 h POST in S, CK was lower (P<0.01) and ORAC was
      higher (P<0.05) following 2D than 1D. CK and ORAC following 2D were blunted and
      augmented, respectively, in response to 1D and antioxidant supplementation
      enhanced this protective effect as indicated by an attenuation of biomarkers of
      muscle damage and a greater antioxidant capacity observed 24 h POST 2D. 

PMID- 25607520
TI  - Landing limb posture in volleyball athletes with patellar tendinopathy: a pilot
      study.
AB  - The aims of this pilot study were to investigate how a novel sagittal plane
      kinematic measurement - the lower extremity contact angle (LECA) - relates to the
      landing dynamics of elite male volleyball athletes with and without patellar
      tendinopathy. The LECA was defined as the angle between the ground and the line
      connecting the center of pressure to the L5S1 marker. 18 athletes (9 with
      patellar tendinopathy and 9 with asymptomatic tendons) completed simulated spike
      jumps while instrumented for kinetic and kinematic analysis using a force
      platform and 3D motion analysis system. The patellar tendinopathic group
      demonstrated a significantly more acute LECA compared to the asymptomatic group
      (65.3 degrees +/-2.2 degrees  vs. 69.1 degrees +/-4.5 degrees ) and was the only
      kinematic or kinetic variable measured to discriminate between the 2 groups. The
      LECA further demonstrated less variability between trials than sagittal plane
      hip, knee, and ankle kinematics. Additionally, the LECA's - and not individual
      joints' - high correlation with the braking impulse ensures its predictive value
      for landing dynamics (r=- 0.890). The LECA has the potential to be a valuable
      tool to help assess jumping athletes in both injury prevention screening and as a
      variable that, if modified, could help alter the maladaptive behavior observed in
      symptomatic athletes. 

PMID- 25607521
TI  - Regulation of mTOR Pathway in Exercise-induced Cardiac Hypertrophy.
AB  - This study was designed to examine whether the mTOR signaling pathway would
      respond to long-term different intensity exercises and to observe the impact of
      exercise upon possible cardiac damage. Male Sprague Dawley rats were randomly
      divided into control group, moderate-intensity exercise group and high-intensity
      exercise group, and each exercise group had 4 observation time points (1-24 h).
      Exercise training lasted 8 weeks with a 2-day break for each week. Serum cTnI was
      measured by ELSIA and myocardium histology was assessed by HE and HBFP. The
      expressions of Akt, mTOR, p70(S6K) and their phosphorylated forms were determined
      by western-blot. Both exercises were effective at inducing cardiac hypertrophy,
      wherein magnitude increased with exercise intensity. The significantly high level
      of serum cTnI in the high-intensity group was accompanied by obvious myocellular
      abnormalities and ischemia in the myocardium. Significant activation of Akt, mTOR
      and p70(S6K) were observed in the moderate exercise group but not in the high
      intensity exercise group. Results indicate that long-term high-intensity exercise
      training would induce cardiac hypertrophy accompanied by damage to the heart,
      entailing a risk of pathological changes. There might be a pivotal regulatory
      role of the mTOR signaling pathway on cardiac hypertrophy after long-term
      moderate exercise, but not after high-intensity exercise. 

PMID- 25607522
TI  - Energy expenditure and fitness response following once weekly hill climbing at
      low altitude.
AB  - This work sought to determine the fitness responses and energy expenditure (EE)
      following once-weekly hill climbing for 16 weeks on different slopes. A cohort of
      98 healthy, sedentary subjects (49 female, 49 male) completed the program at
      their preferred climbing pace. Body composition, resting metabolic rate (RMR) and
      VO2max were measured. EE was measured on 4 slopes (11.6 degrees , 19.9 degrees ,
      14.9 degrees , and 28.6 degrees ) at the subjects' preferred speed. In males,
      weight, body mass index, fat mass significantly decreased (P<0.05), and RMR
      showed an increasing trend, but the difference was not significant (P=0.051). In
      females, the muscle mass increased significantly, and fat (%) and fat mass
      significantly decreased (P<0.05). Absolute and relative of VO2max, ventilation
      (VE) improved significantly in both sexes (P<0.01). Energy expenditure was
      similar on different slopes, but shows gender-specific values of approximately
      50.4 and 33.6 kJ/min for males and females, respectively. The regression equation
      of EE (kJ/min)=[1.724*(female=1, and male=2)+(
      0.072*age)+0.106*weight+0.024*HR+0.136*slope+1.487*velocity]*4.2. In conclusion,
      hill climbing at a subjects' preferred velocity is a vigorous-intensity physical
      activity for energy cost and, performed once weekly, enhances cardiorespiratory
      fitness and reduces fat mass, therefore making it a viable exercise for most
      people. 

PMID- 25607523
TI  - Transcutaneous Electrical Nerve Stimulation Improves Exercise Tolerance in
      Healthy Subjects.
AB  - Transcutaneous electrical nerve stimulation (TENS) increases peripheral blood
      flow by attenuation of the muscle metaboreflex, improving oxygen supply to
      working muscles. We tested the hypothesis that application of TENS at ganglion
      improves exercise performance. 11 subjects underwent constant-work rate tests
      (CWR) to the limit of tolerance (Tlim) while receiving TENS or placebo. Oxygen
      uptake (V.O2), carbon dioxide (V.CO2), minute ventilation (V.E), ventilatory
      equivalent (V.E/V.CO2), heart rate (HR) and oxygen pulse (V.O2/HR) were analyzed
      at isotime separated by percentile and Tlim. V.O2 was lower and V.CO2 was higher
      at 100% of isotime during TENS, while there were no differences in V.E and
      V.E/V.CO2. HR was lower during exercise with TENS, and V.O2/HR increased at peak
      exercise (17.96+/-1.9 vs. 20.38+/-1 ml/min/bpm, P<0.05). TENS increased
      mechanical efficiency at isotime and Tlim (4.10+/-0.50 vs. 3.39+/-0.52%, P<0.05
      and 3.95+/-0.67 vs. 3.77+/-0.45%, P<0.05) and exercise tolerance compared to P
      TENS (390+/-41 vs. 321+/-41 s; P<0.05). Our data shows that the application of
      TENS can potentially increase exercise tolerance and oxygen supply in healthy
      subjects. 

PMID- 25607524
TI  - Heat-stress-induced metabolic changes and altered male reproductive function.
AB  - Heat stress can cause systemic physiological and biochemical alterations in
      living organisms. In reproductive systems, heat stress induces germ cell loss and
      poor quality semen. However, until now, little has been known about such a
      complex regulation process, particularly in the perspective of metabolism. In
      this study, serum, hypothalamus, and epididymis samples derived from male SD
      (Sprague-Dawley) rats being exposed to high environmental temperature (40 
      degrees C) 2 h per day for 7 consecutive days were analyzed using metabonomics
      strategies based on GC/TOFMS. Differentially expressed metabolites reveal that
      the energy metabolism, amino acid neurotransmitters, and monoamine
      neurotransmitters pathways are associated with heat stress, in accordance with
      changes of the three upstream neuroendocrine system pathways in the SNS
      (sympathetic adrenergic system), hypothalamic pituitary adrenal axis (HPA), and
      hypothalamic pituitary testis axis (HPT) axis. Many of these metabolites,
      especially in the epididymis, were found to be up-regulated, presumably due to a
      self-preserving action to resist the environmental hot irritation to maintain
      normal functioning of the male reproductive system. 

PMID- 25607525
TI  - Switching a normal insulator into a topological insulator via electric field with
      application to phosphorene.
AB  - The study of topological insulators has generally involved search of materials
      that have this property as an innate quality, distinct from normal insulators.
      Here we focus on the possibility of converting a normal insulator into a
      topological one by application of an external electric field that shifts
      different bands by different energies and induces a specific band inversion,
      which leads to a topological state. Phosphorene is a two-dimensional (2D)
      material that can be isolated through mechanical exfoliation from layered black
      phosphorus, but unlike graphene and silicene, single-layer phosphorene has a
      large band gap (1.5-2.2 eV). Thus, it was unsuspected to exhibit band inversion
      and the ensuing topological insulator behavior. Using first-principles
      calculations with applied perpendicular electric field F? on few-layer
      phosphorene we predict a continuous transition from the normal insulator to a
      topological insulator and eventually to a metal as a function of F?. The tuning
      of topological behavior with electric field would lead to spin-separated, gapless
      edge states, that is, quantum spin Hall effect. This finding opens the
      possibility of converting normal insulating materials into topological ones via
      electric field and making a multifunctional "field effect topological transistor"
      that could manipulate simultaneously both spin and charge carrier. We use our
      results to formulate some design principles for looking for other 2D materials
      that could have such an electrical-induced topological transition. 

PMID- 25607526
TI  - Food Allergens: Is There a Correlation between Stability to Digestion and
      Allergenicity?
AB  - Food allergy is a major health problem in the Western countries, affecting 3-8%
      of the population. It has not yet been established what makes a dietary protein a
      food allergen. Several characteristics have been proposed to be shared by food
      allergens. One of these is resistance to digestion. This paper reviews data from
      digestibility studies on purified food allergens and evaluates the predictive
      value of digestibility tests on the allergenic potential. We point out that food
      allergens do not necessarily resist digestion. We discuss how the choice of in
      vitro digestibility assay condition and the method used for detection of residual
      intact protein as well as fragments hereof may greatly influence the outcome as
      well as the interpretation of results. The finding that digests from food
      allergens may retain allergenicity, stresses the importance of using
      immunological assays for evaluating the allergenic potential of food allergen
      digestion products. Studies assessing the allergenicity of digestion products, by
      either IgE-binding, elicitation or sensitizing capacity, shows that digestion may
      abolish, decrease, have no effect, or even increase the allergenicity of food
      allergens. Therefore, the predictive value of the pepsin resistance test for
      assessing the allergenic potential of novel proteins can be questioned. 

PMID- 25607527
TI  - Sequencing of first-strand cDNA library reveals full-length transcriptomes.
AB  - Massively parallel strand-specific sequencing of RNA (ssRNA-seq) has emerged as a
      powerful tool for profiling complex transcriptomes. However, many current methods
      for ssRNA-seq suffer from the underrepresentation of both the 5' and 3' ends of
      RNAs, which can be attributed to second-strand cDNA synthesis. The 5' and 3' ends
      of RNA harbour crucial information for gene regulation; namely, transcription
      start sites (TSSs) and polyadenylation sites. Here we report a novel ssRNA-seq
      method that does not involve second-strand cDNA synthesis, as we Directly Ligate
      sequencing Adaptors to the First-strand cDNA (DLAF). This novel method with fewer
      enzymatic reactions results in a higher quality of the libraries than the
      conventional method. Sequencing of DLAF libraries followed by a novel analysis
      pipeline enables the profiling of both 5' ends and polyadenylation sites at near
      base resolution. Therefore, DLAF offers the first genomics tool to obtain the
      'full-length' transcriptome with a single library. 

PMID- 25607530
TI  - Clinical and tumor significance of tropomyosin-1 expression levels in renal cell
      carcinoma.
AB  - Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and
      has been described as one of the deadliest of cancers affecting the genitourinary
      tract. Tropomyosin is a two-stranded alpha-helical coiled coil protein found in
      cell cytoskeletons. One of its isoforms, tropomyosin-1 (TPM1) has been reported
      as a novel tumor-suppressor gene and is downregulated in many solid tumors.
      However the expression level and function of TPM1 in RCC have not yet been
      determined. In the present study, we evaluated the TPM1-4 mRNA and TPM1 protein
      levels in RCC tissue samples. TPM1-overexpressing OSRC-2 and 786-O cell lines
      were also used to investigate the impact of TPM1 on RCC cells. We found that TPM1
      was significantly and specifically downregulated in the RCC tissues. TPM1
      expression was associated with tumor size, smoking status, Fuhrman grade and the
      prognosis of RCC patients. After TPM1 transfection, the migratory and invasive
      abilities of the OSRC-2 and 786-O cell lines were both reduced when compared to
      the control groups. Meanwhile, apoptosis was also enhanced in these two RCC cell
      lines following TPM1 transfection. Taken together, TPM1 exhibits characteristics
      of a tumor-suppressor gene while being overexpressed in RCC cell lines.

PMID- 25607531
TI  - Molecular design of cage iron(II) and cobalt(II,III) complexes with a second
      fluorine-enriched superhydrophobic shell.
AB  - Pentafluorophenylboron-capped iron and cobalt(II) hexachloroclathrochelate
      precursors were obtained by the one-pot template condensation of dichloroglyoxime
      with pentafluorophenylboronic acid on iron and cobalt(II) ions under vigorous
      reaction conditions in trifluoroacetic acid media. These reactive precursors
      easily undergo nucleophilic substitution with (per)fluoroarylthiolate anions,
      giving (per)fluoroarylsulfide macrobicyclic complexes with encapsulated iron and
      cobalt(II) ions; nucleophilic substitution of the cobalt(II)
      hexachloroclathrochelate precursor with a pentafluorophenylsulfide anion gave the
      target hexasulfide monoclathrochelate and the mixed-valence Co(III)Co(II)Co(III)
      bis-clathrochelate as a side product. The complexes obtained were characterized
      using elemental analysis, MALDI-TOF mass spectrometry, IR, UV-Vis, (57)Fe
      Mossbauer (for the X-rayed iron complexes), (1)H, (11)B, (13)C and (19)F NMR
      spectroscopies and by X-ray diffraction; their redox and electrocatalytic
      behaviors were studied using cyclic voltammetry and gas chromatography. As can be
      seen from the single-crystal X-ray diffraction data, the second superhydrophobic
      shell of such caged metal ions is formed by fluorine atoms of both the apical and
      ribbed (per)fluoroaryl peripheral groups. The main bond distances and chelate N=C
      C=N angles in their molecules are similar, but rotational elongation
      (contraction) along the molecular C3-pseudoaxes, accompanied by changes in the
      geometry of the corresponding MN6-coordination polyhedra from a trigonal prism to
      a trigonal antiprism, allowed encapsulating Fe(2+), Co(2+) and Co(3+) ions. The
      nature of an encapsulated metal ion and its oxidation state affect the M-N bond
      lengths, and, for cobalt(ii) clathrochelate with an electronic configuration d(7)
      the Jahn-Teller structural effect is observed as an alternation of the Co-N
      distances. Pentafluorophenylboron-capped hexachloroclathrochelate precursors,
      giving stable catalytically active metal(I)-containing intermediates due to the
      electron-withdrawing effect of their six ribbed chlorine substituents, were found
      to show moderate electrocatalytic activity in a 2H(+)/H2 hydrogen-forming
      reaction. In the case of their ribbed-functionalized sulfide derivatives, the
      strong electron-withdrawing (per)fluoroaryl groups do not stabilize the reduced
      electrocatalytically active metal(i)-containing species as their mesomeric effect
      is absent or substantially decreased by steric hindrances between them.

PMID- 25607532
TI  - Injectable Colloidal Gold for Use in Intrafractional 2D Image-Guided Radiation
      Therapy.
AB  - In the western world, approximately 50% of all cancer patients receive
      radiotherapy alone or in combination with surgery or chemotherapy. Image-guided
      radiotherapy (IGRT) has in recent years been introduced to enhance precision of
      the delivery of radiation dose to tumor tissue. Fiducial markers are often
      inserted inside the tumor to improve IGRT precision and to enable monitoring of
      the tumor position during radiation therapy. In the present article, a liquid
      fiducial tissue marker is presented, which can be injected into tumor tissue
      using thin and flexible needles. The liquid fiducial has high radio-opacity,
      which allows for marker-based image guidance in 2D and 3D X-ray imaging during
      radiation therapy. This is achieved by surface-engineering gold nanoparticles to
      be highly compatible with a carbohydrate-based gelation matrix. The new fiducial
      marker is investigated in mice where they are highly biocompatible and stable
      after implantation. To investigate the clinical potential, a study is conducted
      in a canine cancer patient with spontaneous developed solid tumor in which the
      marker is successfully injected and used to align and image-guide radiation
      treatment of the canine patient. It is concluded that the new fiducial marker has
      highly interesting properties that warrant investigations in cancer patients. 

PMID- 25607528
TI  - ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and
      therapy resistance.
AB  - Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that
      promotes tumor invasion and metastasis by inducing epithelial-mesenchymal
      transition (EMT) in carcinoma cells. EMT not only plays an important role in
      embryonic development and malignant progression, but is also implicated in cancer
      therapy resistance. It has been hypothesized that carcinoma cells that have
      undergone EMT acquire cancer stem cell properties including self-renewal,
      chemoresistance and radioresistance. However, our recent data indicate that ZEB1
      regulates radioresistance in breast cancer cells through an EMT-independent
      mechanism. In this Perspective, we review different mechanisms by which ZEB1
      regulates tumor progression and treatment resistance. Based on studies by us and
      others, we propose that it is specific EMT inducers like ZEB1, but not the
      epithelial or mesenchymal state itself, that dictate cancer stem cell properties.

PMID- 25607529
TI  - Modification of the wobble uridine in bacterial and mitochondrial tRNAs reading
      NNA/NNG triplets of 2-codon boxes.
AB  - Posttranscriptional modification of the uridine located at the wobble position
      (U34) of tRNAs is crucial for optimization of translation. Defects in the U34
      modification of mitochondrial-tRNAs are associated with a group of rare diseases
      collectively characterized by the impairment of the oxidative phosphorylation
      system. Retrograde signaling pathways from mitochondria to nucleus are involved
      in the pathophysiology of these diseases. These pathways may be triggered by not
      only the disturbance of the mitochondrial (mt) translation caused by
      hypomodification of tRNAs, but also as a result of nonconventional roles of mt
      tRNAs and mt-tRNA-modifying enzymes. The evolutionary conservation of these
      enzymes supports their importance for cell and organismal functions.
      Interestingly, bacterial and eukaryotic cells respond to stress by altering the
      expression or activity of these tRNA-modifying enzymes, which leads to changes in
      the modification status of tRNAs. This review summarizes recent findings about
      these enzymes and sets them within the previous data context. 

PMID- 25607533
TI  - Synthesis of the antimicrobial S-linked glycopeptide, glycocin F.
AB  - The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial
      peptide bearing a rare S-linked N-acetylglucosamine (GlcNAc) moiety in addition
      to an O-linked GlcNAc, has been accomplished using a native chemical ligation
      strategy. The synthetic and naturally occurring peptides were compared by HPLC,
      mass spectrometry, NMR and CD spectroscopy, and their stability towards
      chymotrypsin digestion and antimicrobial activity were measured. This is the
      first comprehensive structural and functional comparison of a naturally occurring
      glycocin with an active synthetic analogue. 

PMID- 25607534
TI  - Imperceptible magnetoelectronics.
AB  - Future electronic skin aims to mimic nature's original both in functionality and
      appearance. Although some of the multifaceted properties of human skin may remain
      exclusive to the biological system, electronics opens a unique path that leads
      beyond imitation and could equip us with unfamiliar senses. Here we demonstrate
      giant magnetoresistive sensor foils with high sensitivity, unmatched flexibility
      and mechanical endurance. They are <2 MUm thick, extremely flexible (bending
      radii <3 MUm), lightweight (~3 g m(-2)) and wearable as imperceptible magneto
      sensitive skin that enables proximity detection, navigation and touchless
      control. On elastomeric supports, they can be stretched uniaxially or biaxially,
      reaching strains of >270% and endure over 1,000 cycles without fatigue. These
      ultrathin magnetic field sensors readily conform to ubiquitous objects including
      human skin and offer a new sense for soft robotics, safety and healthcare
      monitoring, consumer electronics and electronic skin devices.

PMID- 25607535
TI  - A DNA hybridization sensor based on catalytic response by platinum deposition.
AB  - We report a novel electrochemical sensing system for single-stranded DNA (ssDNA)
      with a specific sequence based on the catalytic reduction of protons with
      platinum deposited by the electrochemical reduction of chloro-2,2':6',2''
      terpyridine platinum(II) chloride dihydrate (Pt complex) on a glassy carbon (GC)
      electrode. There was no catalytic property observed for proton reduction at the
      GC electrode, while the platinum deposited by the reduction of the Pt complex
      shows the catalytic activity of proton reduction. The intercalation of the Pt
      complex with double-stranded DNA (dsDNA) decreased the concentration of the free
      Pt complex with a concomitant diminution in the electrochemical catalytic current
      due to steric hindrance and a decrease in the diffusion coefficient of the
      intercalated Pt complex. Thus, the catalytic current of proton reduction by
      platinum deposited on a GC electrode decreased with an increase in the
      concentration of target ssDNA, when capture DNA with a complementary sequence was
      present in the solution to form the hybrid dsDNA. A detectable concentration
      range was estimated and found to be 0.1-1.0 MUM. The catalytic current was
      significantly larger than the reduction current of the Pt complex, resulting in
      the sensitive detection of ssDNA. Furthermore, the present method is simply due
      to the immobilization of capture DNA being unnecessary.

PMID- 25607536
TI  - A minimal physical model captures the shapes of crawling cells.
AB  - Cell motility in higher organisms (eukaryotes) is crucial to biological functions
      ranging from wound healing to immune response, and also implicated in diseases
      such as cancer. For cells crawling on hard surfaces, significant insights into
      motility have been gained from experiments replicating such motion in vitro. Such
      experiments show that crawling uses a combination of actin treadmilling
      (polymerization), which pushes the front of a cell forward, and myosin-induced
      stress (contractility), which retracts the rear. Here we present a simplified
      physical model of a crawling cell, consisting of a droplet of active polar fluid
      with contractility throughout, but treadmilling connected to a thin layer near
      the supporting wall. The model shows a variety of shapes and/or motility regimes,
      some closely resembling cases seen experimentally. Our work strongly supports the
      view that cellular motility exploits autonomous physical mechanisms whose
      operation does not need continuous regulatory effort. 

PMID- 25607537
TI  - Dendritic silica nanoparticles synthesized by a block copolymer-directed seed
      regrowth approach.
AB  - A facile seed regrowth method is presented for the preparation of a new type of
      colloidal dendritic silica nanoparticles (DSNPs) with unique Konpeito-like
      morphology and high surface area (~400 m(2) g(-1)). Growth of silica
      nanoprotrusions on the surfaces of colloidal silica nanoparticles proceeds by
      hydrolysis and polycondensation of tetraethoxysilane (TEOS) in the presence of a
      PEO-PPO-PEO-type block copolymer (Pluronic F127) under controlled pH conditions.
      The polymers adsorbed on the seed surface play a crucial role in the formation of
      DSNPs. DSNPs with controllable size (28-85 nm) and narrow size distributions can
      be obtained by using monodisperse silica nanoparticles with various sizes as
      seeds. The surface morphology of DSNPs is tunable by changing the concentration
      of TEOS. Additionally, novel dendritic silica nanochains are prepared using one
      dimensionally assembled silica nanoparticles as the seeds. 

PMID- 25607538
TI  - New microfluidic-based sampling procedure for overcoming the hematocrit problem
      associated with dried blood spot analysis.
AB  - Hematocrit (Hct) is one of the most critical issues associated with the
      bioanalytical methods used for dried blood spot (DBS) sample analysis. Because
      Hct determines the viscosity of blood, it may affect the spreading of blood onto
      the filter paper. Hence, accurate quantitative data can only be obtained if the
      size of the paper filter extracted contains a fixed blood volume. We describe for
      the first time a microfluidic-based sampling procedure to enable accurate blood
      volume collection on commercially available DBS cards. The system allows the
      collection of a controlled volume of blood (e.g., 5 or 10 MUL) within several
      seconds. Reproducibility of the sampling volume was examined in vivo on capillary
      blood by quantifying caffeine and paraxanthine on 5 different extracted DBS spots
      at two different time points and in vitro with a test compound, Mavoglurant, on
      10 different spots at two Hct levels. Entire spots were extracted. In addition,
      the accuracy and precision (n = 3) data for the Mavoglurant quantitation in blood
      with Hct levels between 26% and 62% were evaluated. The interspot precision data
      were below 9.0%, which was equivalent to that of a manually spotted volume with a
      pipet. No Hct effect was observed in the quantitative results obtained for Hct
      levels from 26% to 62%. These data indicate that our microfluidic-based sampling
      procedure is accurate and precise and that the analysis of Mavoglurant is not
      affected by the Hct values. This provides a simple procedure for DBS sampling
      with a fixed volume of capillary blood, which could eliminate the recurrent Hct
      issue linked to DBS sample analysis. 

PMID- 25607540
TI  - Visual attention during spatial language comprehension.
AB  - Spatial terms such as "above", "in front of", and "on the left of" are all
      essential for describing the location of one object relative to another object in
      everyday communication. Apprehending such spatial relations involves relating
      linguistic to object representations by means of attention. This requires at
      least one attentional shift, and models such as the Attentional Vector Sum (AVS)
      predict the direction of that attention shift, from the sausage to the box for
      spatial utterances such as "The box is above the sausage". To the extent that
      this prediction generalizes to overt gaze shifts, a listener's visual attention
      should shift from the sausage to the box. However, listeners tend to rapidly look
      at referents in their order of mention and even anticipate them based on
      linguistic cues, a behavior that predicts a converse attentional shift from the
      box to the sausage. Four eye-tracking experiments assessed the role of overt
      attention in spatial language comprehension by examining to which extent visual
      attention is guided by words in the utterance and to which extent it also shifts
      "against the grain" of the unfolding sentence. The outcome suggests that
      comprehenders' visual attention is predominantly guided by their interpretation
      of the spatial description. Visual shifts against the grain occurred only when
      comprehenders had some extra time, and their absence did not affect comprehension
      accuracy. However, the timing of this reverse gaze shift on a trial correlated
      with that trial's verification time. Thus, while the timing of these gaze shifts
      is subtly related to the verification time, their presence is not necessary for
      successful verification of spatial relations. 

PMID- 25607539
TI  - A toolkit for ARB to integrate custom databases and externally built phylogenies.
AB  - Researchers are perpetually amassing biological sequence data. The computational
      approaches employed by ecologists for organizing this data (e.g. alignment,
      phylogeny, etc.) typically scale nonlinearly in execution time with the size of
      the dataset. This often serves as a bottleneck for processing experimental data
      since many molecular studies are characterized by massive datasets. To keep up
      with experimental data demands, ecologists are forced to choose between
      continually upgrading expensive in-house computer hardware or outsourcing the
      most demanding computations to the cloud. Outsourcing is attractive since it is
      the least expensive option, but does not necessarily allow direct user
      interaction with the data for exploratory analysis. Desktop analytical tools such
      as ARB are indispensable for this purpose, but they do not necessarily offer a
      convenient solution for the coordination and integration of datasets between
      local and outsourced destinations. Therefore, researchers are currently left with
      an undesirable tradeoff between computational throughput and analytical
      capability. To mitigate this tradeoff we introduce a software package to leverage
      the utility of the interactive exploratory tools offered by ARB with the
      computational throughput of cloud-based resources. Our pipeline serves as
      middleware between the desktop and the cloud allowing researchers to form local
      custom databases containing sequences and metadata from multiple resources and a
      method for linking data outsourced for computation back to the local database. A
      tutorial implementation of the toolkit is provided in the supporting information,
      S1 Tutorial. AVAILABILITY: http://www.ece.drexel.edu/gailr/EESI/tutorial.php.

PMID- 25607541
TI  - The relationship between internalising symptom development and academic
      attainment in early adolescence.
AB  - Evidence for the longitudinal associations between internalising symptom
      development and academic attainment is sparse and results from existing studies
      are largely inconclusive. The approaches that have been used in existing studies
      examining this relationship have in common the limitation of grouping together
      all individuals in the sample which makes the assumption that the relationship
      between time, symptoms and attainment across all individuals is the same. The
      current study aimed to use heterogeneous trajectories of symptom development to
      examine the longitudinal associations between internalising symptom development
      and change in academic attainment over a three years period in early adolescence,
      a key period for internalising symptom development. Internalising symptoms were
      assessed for 3 consecutive years in a cohort from age 11-14 years (n = 2647, mean
      age at T1 = 11.7 years). National standardised test scores prior to the first
      wave and subsequent to the last wave were used as measures of academic
      attainment. Heterogeneous symptom development trajectories were identified using
      latent class growth analysis and socio-demographic correlates, such as gender,
      SES and ethnicity, of the different trajectory groupings were investigated.
      Derived trajectory groupings were examined as predictors of subsequent academic
      attainment, controlling for prior attainment. Results demonstrate that symptom
      trajectories differentially predicted change in academic attainment with
      increasing trajectories associated with significantly worse academic outcomes
      when compared to pupils with low levels of symptoms in all waves. Hence, a
      trajectory based approach provides a more nuanced breakdown of complexities in
      symptom development and their differential relationships with academic outcomes
      and in doing so helps clarify the longitudinal relationship between these two key
      domains of functioning in early adolescence. 

PMID- 25607542
TI  - Theoretical insights into the functioning of metallopeptidases and their
      synthetic analogues.
AB  - CONSPECTUS: The selective hydrolysis of a peptide or amide bond (-(O?)C-NH-) by a
      synthetic metallopeptidase is required in a wide range of biological,
      biotechnological, and industrial applications. In nature, highly specialized
      enzymes known as proteases and peptidases are used to accomplish this daunting
      task. Currently, many peptide bond cleaving enzymes and synthetic reagents have
      been utilized to achieve efficient peptide hydrolysis. However, they possess some
      serious limitations. To overcome these inadequacies, a variety of metal complexes
      have been developed that mimic the activities of natural enzymes
      (metallopeptidases). However, in comparison to metallopeptidases, the hydrolytic
      reactions facilitated by their existing synthetic analogues are considerably
      slower and occur with lower catalytic turnover. This could be due to the
      following reasons: (1) they lack chemical properties of amino acid residues found
      within enzyme active sites; (2) they contain a higher metal coordination number
      compared with naturally occurring enzymes; and (3) they do not have access to
      second coordination shell residues that provide substantial rate enhancements in
      enzymes. Additionally, the critical structural and mechanistic information
      required for the development of the next generation of synthetic
      metallopeptidases cannot be readily obtained through existing experimental
      techniques. This is because most experimental techniques cannot follow the
      individual chemical steps in the catalytic cycle due to the fast rate of enzymes.
      They are also limited by the fact that the diamagnetic d(10) Zn(II) center is
      silent to electronic, electron spin resonance, and (67)Zn NMR spectroscopies.
      Therefore, we have employed molecular dynamics (MD), quantum mechanics (QM), and
      hybrid quantum mechanics/molecular mechanics (QM/MM) techniques to derive this
      information. In particular, the role of the metal ions, ligands, and
      microenvironment in the functioning of mono- and binuclear metal center
      containing enzymes such as insulin degrading enzyme (IDE) and bovine lens leucine
      aminopeptidase (BILAP), respectively, and their synthetic analogues have been
      investigated. Our results suggested that in the functioning of IDE, the chemical
      nature of the peptide bond played a role in the energetics of the reaction and
      the peptide bond cleavage occurred in the rate-limiting step of the mechanism. In
      the cocatalytic mechanism used by BILAP, one metal center polarized the scissile
      peptide bond through the formation of a bond between the metal and the carbonyl
      group of the substrate, while the second metal center delivered the hydroxyl
      nucleophile. The Zn(N3) [Zn(His, His, His)] core of matrix metalloproteinase was
      better than the Zn(N2O) [Zn(His, His, Glu)] core of IDE for peptide hydrolysis.
      Due to the synergistic interaction between the two metal centers, the binuclear
      metal center containing Pd2(MU-OH)([18]aneN6)](4+) complex was found to be ~100
      times faster than the mononuclear [Pd(H2O)4](2+) complex. A successful small
      molecule synthetic analogue of a mononuclear metallopeptidase must contain a
      metal with a strong Lewis acidity capable of reducing the pKa of its water ligand
      to less than 7. Ideally, the metal center should include three ligands with low
      basicity. The steric effects or strain exerted by the microenvironment could be
      used to weaken the metal-ligand interactions and increase the activity of the
      metallopeptidase.

PMID- 25607544
TI  - Effects of different per translational kinetics on the dynamics of a core
      circadian clock model.
AB  - Living beings display self-sustained daily rhythms in multiple biological
      processes, which persist in the absence of external cues since they are generated
      by endogenous circadian clocks. The period (per) gene is a central player within
      the core molecular mechanism for keeping circadian time in most animals.
      Recently, the modulation PER translation has been reported, both in mammals and
      flies, suggesting that translational regulation of clock components is important
      for the proper clock gene expression and molecular clock performance. Because
      translational regulation ultimately implies changes in the kinetics of
      translation and, therefore, in the circadian clock dynamics, we sought to study
      how and to what extent the molecular clock dynamics is affected by the kinetics
      of PER translation. With this objective, we used a minimal mathematical model of
      the molecular circadian clock to qualitatively characterize the dynamical changes
      derived from kinetically different PER translational mechanisms. We found that
      the emergence of self-sustained oscillations with characteristic period,
      amplitude, and phase lag (time delays) between per mRNA and protein expression
      depends on the kinetic parameters related to PER translation. Interestingly,
      under certain conditions, a PER translation mechanism with saturable kinetics
      introduces longer time delays than a mechanism ruled by a first-order kinetics.
      In addition, the kinetic laws of PER translation significantly changed the
      sensitivity of our model to parameters related to the synthesis and degradation
      of per mRNA and PER degradation. Lastly, we found a set of parameters, with
      realistic values, for which our model reproduces some experimental results
      reported recently for Drosophila melanogaster and we present some predictions
      derived from our analysis. 

PMID- 25607545
TI  - Conditions in home and transplant soils have differential effects on the
      performance of diploid and allotetraploid anthericum species.
AB  - Due to increased levels of heterozygosity, polyploids are expected to have a
      greater ability to adapt to different environments than their diploid ancestors.
      While this theoretical pattern has been suggested repeatedly, studies comparing
      adaptability to changing conditions in diploids and polyploids are rare. The aim
      of the study was to determine the importance of environmental conditions of
      origin as well as target conditions on performance of two Anthericum species,
      allotetraploid A. liliago and diploid A. ramosum and to explore whether the two
      species differ in the ability to adapt to these environmental conditions.
      Specifically, we performed a common garden experiment using soil from 6
      localities within the species' natural range, and we simulated the forest and
      open environments in which they might occur. We compared the performance of
      diploid A. ramosum and allotetraploid A. liliago originating from different
      locations in the different soils. The performance of the two species was not
      affected by simulated shading but differed strongly between the different target
      soils. Growth of the tetraploids was not affected by the origin of the plants. In
      contrast, diploids from the most nutrient poor soil performed best in the richest
      soil, indicating that diploids from deprived environments have an increased
      ability to acquire nutrients when available. They are thus able to profit from
      transfer to novel nutrient rich environments. Therefore, the results of the study
      did not support the general expectation that the polyploids should have a greater
      ability than the diploids to adapt to a wide range of conditions. In contrast,
      the results are in line with the observation that diploids occupy a wider range
      of environments than the allotetraploids in our system. 

PMID- 25607546
TI  - Gene sequence analysis and screening of feature genes in spinal cord injury.
AB  - The aim of the present study was to screen for feature genes associated with
      spinal cord injury (SCI), in order to identify the underlying pathogenic
      mechanisms. Differentially expressed genes were screened for using pre-processing
      data. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was
      performed to analyze and identify the genes involved in pathways associated with
      SCI. Subsequently, Gene Ontology enrichment analysis and Uniprot tissue analysis
      were used to screen out genes specifically expressed in spinal cord tissue. In
      addition, a protein-protein interaction network was used to demonstrate possible
      associations among SCI-associated feature genes. Finally, a link was identified
      between feature genes and SCI by analyzing protein domains in coding areas of the
      three feature genes. The cytochrome c oxidase subunit Va, adenosine triphosphate
      (ATP) synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1 and
      cardiac muscle and mitochondrial beta-F1-ATPase may be downregulated in SCI,
      resulting in destruction of the mitochondrial electron transport chain and
      membrane-bound enzyme complexes/ion transporters, thus, affecting the normal
      function of nerves. The three screened feature genes have the potential to become
      candidate target molecules to monitor, diagnose and treat SCI and may be
      beneficial for the early diagnosis and therapeutic control of the condition.

PMID- 25607543
TI  - The Lung-Liver Axis: A Requirement for Maximal Innate Immunity and
      Hepatoprotection during Pneumonia.
AB  - The hepatic acute-phase response (APR), stimulated by injury or inflammation, is
      characterized by significant changes in circulating acute-phase protein (APP)
      concentrations. Although individual functions of liver-derived APPs are known,
      the net consequence of APP changes is unclear. Pneumonia, which induces the APR,
      causes an inflammatory response within the airspaces that is coordinated largely
      by alveolar macrophages and is typified by cytokine production, leukocyte
      recruitment, and plasma extravasation, the latter of which may enable delivery of
      hepatocyte-derived APPs to the infection site. To determine the functional
      significance of the hepatic APR during pneumonia, we challenged APR-null mice
      lacking hepatocyte signal transducer and activator of transcription 3 (STAT3) and
      v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) with
      Escherichia coli in the airspaces. APR-null mice displayed ablated APP induction,
      significantly increased mortality, liver injury and apoptosis, and a trend toward
      increased bacterial burdens. TNF-alpha neutralization reversed hepatotoxicity,
      but not mortality, suggesting that APR-dependent survival is not solely due to
      hepatoprotection. After a milder (nonlethal) E. coli infection, hepatocyte
      specific mutations decreased APP concentrations and pulmonary inflammation in
      bronchoalveolar lavage fluid. Cytokine expression in airspace macrophages, but
      not other airspace or circulating cells, was significantly dependent on APP
      extravasation into the alveoli. These data identify a novel signaling axis
      whereby the liver response enhances macrophage activation and pulmonary
      inflammation during pneumonia. Although hepatic acute-phase changes directly curb
      injury induced by TNF-alpha in the liver itself, APPs downstream of these same
      signals promote survival in association with innate immunity in the lungs, thus
      demonstrating a critical role for the lung-liver axis during pneumonia. 

PMID- 25607547
TI  - Correction: kernel density surface modelling as a means to identify significant
      concentrations of vulnerable marine ecosystem indicators.

PMID- 25607548
TI  - Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal
      ablation model.
AB  - The pathogenic role of inflammation and oxidative stress in chronic kidney
      disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has
      demonstrated significant renoprotection in experimental nephropathies. Moreover,
      the inclusion of natural antioxidants derived from food and herbal extracts (such
      as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD
      progression has been largely tested. Brazilian propolis is a honeybee product,
      whose anti-inflammatory, antimicrobial and antioxidant effects have been widely
      shown in models of sepsis, cancer, skin irritation and liver fibrosis.
      Furthermore, previous studies demonstrated that this compound promotes
      vasodilation and reduces hypertension. However, potential renoprotective effects
      of propolis in CKD have never been investigated. The aim of this study was to
      evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP),
      in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and
      were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of
      surgery; when rats already exhibited marked hypertension and proteinuria. Animals
      were observed for 90 days from the surgery day, when Nx+RP group showed
      significant reduction of hypertension, proteinuria, serum creatinine retention,
      glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared
      to age-matched untreated Nx rats, which worsened progressively over time. In
      conclusion, RP treatment attenuated hypertension and structural renal damage in
      Nx model. Reduction of renal inflammation and oxidative stress could be a
      plausible mechanism to explain this renoprotection. 

PMID- 25607550
TI  - Therapeutic update: Onychomycosis.

PMID- 25607551
TI  - Colloidal oatmeal formulations and the treatment of atopic dermatitis.
AB  - Colloidal oatmeal suspensions are currently available in bath soaps, shampoos,
      shaving gels, and moisturizing creams, and several studies have been conducted
      that demonstrate the efficacy and safety of colloidal oatmeal for the treatment
      of inflammatory skin conditions. The diverse chemical polymorphism of oats
      translates into numerous clinical utilities for atopic dermatitis (AD) and
      eczema. Avenanthramides are the principle polyphenolic antioxidants in oats, and
      they have been shown to assuage inflammation in murine models of contact
      hypersensitivity and neurogenic inflammation and also reduce pruritogen-induced
      scratching in a murine itch model. Moreover, avenanthramides are a potent
      antioxidant. This paper will discuss various studies that have found colloidal
      oatmeal compounds to be beneficial in the treatment of AD and also as adjunctive
      treatments for AD.

PMID- 25607552
TI  - Efinaconazole topical, 10% for the treatment of toenail onychomycosis in patients
      with diabetes.
AB  - OBJECTIVE: To evaluate efficacy, safety, and tolerability efinaconazole topical
      solution, 10% in diabetic patients with onychomycosis. METHODS: A post-hoc
      analysis of 112 patients, aged 29-70 years, randomized to receive efinaconazole
      topical solution, 10% or vehicle from two identical multicenter, double-blind,
      vehicle-controlled 48-week studies evaluating safety and efficacy. The primary
      end point was complete cure rate (0% clinical involvement of target toenail, and
      both negative potassium hydroxide examination and fungal culture) at week 52.
      RESULTS: Mycologic cure rates (OC) were significantly greater with efinaconazole
      (56.5% and 56.3% in diabetic and non-diabetic patients respectively) compared to
      vehicle (P=0.016 and P<0.001, respectively). The primary end point, complete
      cure, was also greater for efinaconazole (13.0% and 18.8%, respectively vs 3.7%
      and 4.7%). Treatment success (percent affected target toenail <=10%) for
      efinaconazole was 40.8% and 47.7%, respectively vs 18.5% and 18.2% with vehicle.
      There was no statistically significant difference between the diabetic and non
      diabetic populations for any efficacy endpoint. Adverse events associated with
      efinaconazole were local site reactions and clinically similar to vehicle.
      CONCLUSIONS: Once daily efinaconazole topical solution, 10% may provide a useful
      topical option in the treatment of diabetic patients with onychomycosis.

PMID- 25607553
TI  - Treatment of recalcitrant warts with occlusive warming patches.
AB  - Prior studies have identified local heat therapy as a treatment for recalcitrant
      warts. We have employed a thermal pad that raises local temperature to 42-43oC
      for at least 2 hours in a proof of concept study of three patients with
      recalcitrant warts. The recalcitrant warts cleared in all three patients
      beginning in the fourth and fifth weeks after daily treatment with the pads.
      There were no adverse events. We conclude that the timing of clearance following
      use of these thermal pads is likely via direct viral killing and immunologic
      mechanisms. Further controlled trials are underway.

PMID- 25607549
TI  - Autophagy in the fight against tuberculosis.
AB  - Tuberculosis (TB), a chronic infectious disease mainly caused by the tubercle
      bacillus Mycobacterium tuberculosis, is one of the world's deadliest diseases
      that has afflicted humanity since ancient times. Although the number of people
      falling ill with TB each year is declining, its incidence in many developing
      countries is still a major cause of concern. Upon invading host cells by
      phagocytosis, M. tuberculosis can replicate within infected cells by arresting
      the maturation of the phagosome whose function is to target the pathogen for
      elimination. Host cells have mechanisms of controlling this evasion by inducing
      autophagy, an elaborate cellular process that targets bacteria for progressive
      elimination, decreasing bacterial loads within infected cells. In addition,
      autophagy activation also aids in the control of inflammation, contributing to a
      more efficient innate immune response against M. tuberculosis. Several innovative
      TB therapies have been envisaged based on autophagy manipulation, with some of
      them revealing high potential for future clinical trials and eventual
      implementation in healthcare systems. Thus, this review highlights the recent
      advances on the innate immune response regulation by autophagy upon M.
      tuberculosis infection and the promising new autophagy-based therapies for TB. 

PMID- 25607554
TI  - A phase 3, randomized, double-blind, placebo-controlled study evaluating the
      efficacy and safety of alitretinoin (BAL4079) in the treatment of severe chronic
      hand eczema refractory to potent topical corticosteroid therapy.
AB  - Severe chronic hand eczema (sCHE) is a persistent, disfiguring disease that
      responds poorly to conventional treatment and causes substantial physical and
      psychological disability. The objective of this study was to evaluate efficacy
      and safety of oral alitretinoin in sCHE in a Phase 3, multicenter, randomized,
      double-blind, placebo-controlled, parallel-group study comparing alitretinoin
      with placebo. Efficacy was assessed every 4 weeks during treatment and 4 weeks
      after end of treatment (EOT, 24 weeks); responders were assessed every 4 weeks
      for a further 48 weeks after EOT. The study was conducted at academic and private
      dermatology centers. The participants were 596 patients with sCHE refractory to
      potent topical corticosteroids. Patients were treated with daily oral
      alitretinoin 30 mg or placebo for up to 24 weeks. Primary endpoint was proportion
      of responding patients based on Physician Global Assessment (PGA) of "clear" or
      "almost clear" at EOT. Key secondary endpoints: Patient Global Assessment (PaGA),
      change in modified Total Lesion Symptom Score (mTLSS), time to response (TTR),
      extent of disease at EOT, and duration of response (DOR). At EOT, 40% of
      alitretinoin-treated patients were responders vs 15% placebo-treated patients
      (odds ratio [OR] = 3.78; P < .001); a greater proportion of alitretinoin-treated
      patients achieved a PaGA of "cleared" or "almost cleared" (OR = 4.05; P< .001). A
      greater decrease in mTLSS occurred from baseline to EOT in alitretinoin- vs
      placebo-treated patients (treatment difference -24% P< .001). Median TTR for
      responders at EOT was shorter with alitretinoin vs placebo (65 vs 117 days; P<
      .001). Greater decreases in extent of disease at EOT were observed with
      alitretinoin vs placebo (treatment difference -22%; P< .001). The most common
      treatment-emergent adverse event was headache. Alitretinoin significantly
      improved signs/symptoms of sCHE, was well tolerated in patients refractory to
      potent topical corticosteroids, and may provide benefit to this population.

PMID- 25607555
TI  - Split-face vitamin C consumer preference study.
AB  - BACKGROUND: Vitamin C is commonly used to treat aged skin. It has shown
      regenerative effects on skin wrinkles, texture, strength, and evenness of tone
      through its roles as an antioxidant, tyrosinase inhibitor, and inducer of
      collagen synthesis. Available vitamin C formulations on the anti-aging skin care
      market vary by their pH, packaging, and vehicle, which may decrease absorption,
      and therefore, the efficacy of the product. OBJECTIVE: The purpose of this study
      was to assess the subjective efficacy, wearability, tolerance and overall
      preference of two professional vitamin C topical serums and sunscreens in
      Caucasian females using a split face method. METHODS: A virtual split-face study
      of 39 Caucasian women compared two popular vitamin C and SPF product combinations
      - C-ESTA(r) Face Serum and Marini Physical Protectant SPF 45 (Jan Marini Skin,
      San Jose, CA; Products A) and CE Ferulic(r) and Physical Fusion UV Defense SPF 50
      (Products B; SkinCeuticals Inc, Garland, TX). The products were assigned to each
      subject's left or right side of the face, and subjects rated and compared
      products through 5 online surveys at baseline, 24 hours, days 3, 7, and 14.
      RESULTS: Over 86% of the 35 subjects who completed the study preferred the smell
      and 83% preferred the feel and application of vitamin C Serum A over Serum B.
      Seventy-one percent of subjects preferred the feel and application of Sunscreen A
      over Sunscreen B. Results also showed a significant skin texture improvement and
      skin tone with Products A vs Product B. Products A trended higher for multiple
      additional categories. CONCLUSIONS: Products A exhibited superior anti-aging
      benefits than Products B. Subjects preferred the smell, feel, and application of
      Products A and experienced significantly less irritation than Products B.
      Overall, Products A were preferred over Products B with subjects willing to pay
      more for Products A over Products B.

PMID- 25607556
TI  - The effects of topical L-selenomethionine on protection against UVB-induced skin
      cancer when given before, during, and after UVB exposure.
AB  - Previous studies in mice have shown that topical L-selenomethionine (SeMet) can
      prevent UVB-induced skin cancer when applied continuously before, during, and
      after the radiation exposure. With topical application of SeMet, selenium levels
      were shown to increase in the skin and liver, as well as in tumor tissue. Thus,
      possibly, the timing of SeMet application could affect the degree of inhibition
      of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The
      goal of this research was to determine whether topical SeMet best inhibits UV
      induced skin cancer if (a) begun before and continued during and after UVB
      exposure, (b) if begun before UVB-exposure and discontinued when tumors are first
      clinically detected, or (c) if begun only after tumors are first detected and
      continued thereafter. Groups of ten Skh: 1 hairless, non-pigmented mice were
      treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle
      lotion applied either (a) before, during, and after UV exposure, (b) before UV
      radiation and continued only until the first tumor was detected, or (c) only
      after the first tumor was detected. In all cases, UV irradiation was discontinued
      at the time of detection of the first tumor. Optimal inhibition of skin cancer
      was achieved by application of topical SeMet before, during, and after exposure;
      significant protection was also attained with application only after the onset of
      tumors. Notably, statistically significant protection was not seen with SeMet
      application only prior to tumor detection. These results suggest that even
      beginning SeMet supplementation late in the process of tumorigenesis can help
      protect from UV-induced photodamage and skin cancer.

PMID- 25607557
TI  - Gender-based variability in disease presentation in pemphigus vulgaris.
AB  - Pemphigus vulgaris is a chronic autoimmune blistering disorder of the skin. As
      with many autoimmune diseases, a female predominance in pemphigus vulgaris is
      well established. The genetic and physiological basis for this gender bias is not
      well understood. Moreover, it is unclear whether the affect of gender extends
      beyond disease susceptibility to influence disease presentation. To address this
      issue, we performed a comprehensive analysis of 72 male and 125 female pemphigus
      vulgaris patients across a set of defined demographic (HLA type, ethnicity) and
      clinical (age at disease onset, anti-desmoglein antibody levels, site of lesions,
      and history of autoimmune disease) factors. We find that male patients are more
      likely to present with disease onset before age 40 than females. Additionally, we
      find that males have increased cutaneous involvement and display greater co
      expression of anti-Dsg1 and anti-Dsg3 antibodies, while females tend to have
      mucosal predominance and stronger personal and family histories of autoimmunity.
      We do not find any differences in the distribution of HLA type or ethnicity
      between male and female pemphigus vulgaris patients. Our findings establish that
      gender does influence disease presentation in pemphigus vulgaris, supporting a
      role for genetic and hormonal factors in immune dysregulation and perpetuation of
      the autoimmune phenotype.

PMID- 25607558
TI  - Topical cyclosporine versus emulsion vehicle for the treatment of brittle nails:
      a randomized controlled pilot study.
AB  - BACKGROUND: Limited options are available for the treatment of brittle nail
      syndrome. OBJECTIVE: To assess the efficacy and safety of topical cyclosporine
      emulsion (CsAE) versus emulsion (vehicle) alone in the treatment of brittle nail
      syndrome. RESULTS: Twenty-four patients were randomized to topical CsAE emulsion
      or emulsion (vehicle) for 24 weeks. Four fingernails of each patient were
      included; the 2 most severe brittle nails and the second most normal nail were
      treated with the same medication. The fourth nail, the most normal nail, remained
      untreated and was used to assess nail growth. The prespecified primary endpoint
      was change from baseline in Physician Global Assessment (PGA) score (0 to 5
      scale) at each follow-up visit. Safety evaluations were conducted at each visit.
      RESULTS: In the intent-to-treat population (n=12 for each treatment arm), the PGA
      score for treated nails improved from baseline (CsAE, 0.7 to 1.4; emulsion, 0.7
      to 1.5; P<0.05 for each), with no significant between-group differences.
      Untreated nails did not improve in overall appearance (0.0 to 0.3 grade; P>0.05).
      Statistically and clinically significant improvement from baseline was reported
      for nail length/appearance in both CsAE and vehicle groups. LIMITATIONS: Sample
      size was relatively small. The difference in PGA between treated and untreated
      nails was not analyzed. Baseline disease severity may have been too mild,
      limiting detection of efficacy. CONCLUSIONS: Both CsAE and emulsion vehicle
      applied topically appeared to improve signs and symptoms of brittle nail syndrome
      and were well tolerated. These findings warrant corroboration in a larger
      population and inclusion of comparison with an inactive control and a higher
      concentration of CsAE, the former which may help in distinguishing the efficacy
      of vehicle emulsion from CsAE.

PMID- 25607561
TI  - Hailey-Hailey disease and review of management.
AB  - IMPORTANCE: Hailey-Hailey disease, or familial benign chronic pemphigus, is a
      rare genodermatosis that can be challenging for both patients and dermatologists
      as the disease can significantly impact patients' quality of life and is often
      difficult to control. In recalcitrant cases, multiple treatment modalities are
      often needed to obtain benefit. Unfortunately, most of the available evidence
      pertaining to treatment is scattered across case reports and retrospective
      analyses. OBJECTIVE: To review successful treatments of Hailey-Hailey, synthesize
      the evidence, and provide recommendations for therapy. FINDINGS: The best
      evidence exists for treatment with topical steroids and topical antimicrobials.
      Refractory disease has shown the most benefit with addition of oral antibiotics,
      excisional procedures and botulinum toxin A. Other therapies are described but
      with much less supporting evidence. CONCLUSIONS: Herein we review the literature
      to identify successful treatments for Hailey-Hailey disease. We have outlined the
      treatments with the most evidence. The difficult nature of treating this disease
      requires that clinicians approach each patient differently. The literature shows
      that no one regiment works for all patients.

PMID- 25607560
TI  - Measuring occipital scalp laxity before donor strip harvesting in hair
      transplantation.
AB  - BACKGROUND: Occipital scars from donor strip harvesting during hair
      transplantation are an important cosmetic concern. Scalp laxity has an important
      role, due to the more frequent use of dense packing and megasession
      transplantation, which requires more grafts and creates a wider, longer donor
      scar. OBJECTIVE: To determine if the use of a simple, objective measurement of
      occipital scalp laxity could reduce scar length by allowing for adjustment of
      donor strip harvesting during hair transplantation. METHODS AND MATERIALS: This
      retrospective study included data from 39 patients who underwent hair
      transplantation with >2000 follicular units: 25 patients underwent measurement of
      occipital scalp laxity (measurement group); the other 14 did not (control group).
      We measured and calculated preoperative scalp parameters for hair
      transplantation, including follicular unit density at occipital scalp, length and
      width of the donor strip, and estimated total number of grafts. All patients
      underwent standard follicular-unit hair transplantation, at which time the actual
      total number of grafts was determined. RESULTS: Mean occipital follicular unit
      density in the measurement group was 74.16 follicles per cm2, which did not
      significantly differ from the controls (73.29; t=0.410, d.f.=37, P>0.05). The
      mean length of the occipital surgical wound was significantly shorter in the
      measurement group than in the controls (19.16 vs 27.50 cm, respectively;
      t=10.412, d.f.=37, P<0.05). The difference between the estimated and actual total
      number of grafts was significant in the measurement group (2139.44 vs 2397.64,
      respectively; paired t=3.095, d.f.=48, P<0.05) but not in the control group
      (2277.71 vs 2296.71, respectively; paired t=0.175, d.f.=26, P>0.05). Accuracy in
      estimating the total number of grafts was poor for the measurement group, as the
      number of actual grafts significantly exceeded estimates. CONCLUSION: Use of data
      from a simple, objective method to measure occipital scalp laxity simplified
      adjustment of strip harvesting, allowed for use of wider strips, and resulted in
      smaller donor wounds and scars from hair transplantation; however, accuracy in
      estimating the total number of grafts was reduced.

PMID- 25607559
TI  - Assessment of cardiovascular risk in patients with moderate to severe plaque
      psoriasis.
AB  - BACKGROUND: Cardiovascular morbidity and mortality have been demonstrated to be
      greater in psoriasis patients than in the general population. Our study aimed to
      assess the 10-year cardiovascular risk in patients with moderate to severe
      psoriasis compared with those suffering from other dermatological diseases, using
      the calibrated Framingham risk score and the Systematic Coronary Risk Evaluation
      (SCORE) risk charts. METHODS: A cross-sectional, multicentre study was made of
      477 patients, of whom 238 had moderate to severe psoriasis (cases) and 239 were
      diagnosed with another dermatological disease (controls). RESULTS: The proportion
      of patients with intermediate to high 10-year cardiovascular risk using the
      Framingham equation was significantly higher among psoriasis patients (38.5%;
      80/208) than among the controls with other dermatological diseases (23.4%;
      50/214, P<.05). No significant differences were observed between the 2 groups
      with respect to cardiovascular risk using the SCORE risk charts (P=.591). The
      case group included a greater proportion of obese and morbidly obese patients, as
      well as patients with higher triglyceride and low density lipoprotein cholesterol
      levels (P<.05); while high density lipoprotein cholesterol levels were
      significantly more favorable in patients in the control group (P<.05).
      CONCLUSIONS: Cardiovascular risk was greater in patients with moderate to severe
      psoriasis than in patients with other dermatological conditions, suggesting that
      early detection and tailored management of risk factors is essential to reducing
      cardiovascular morbidity in these patients.

PMID- 25607562
TI  - Comparison of the efficacy of long-pulsed Nd:YAG laser intervention for treatment
      of onychomycosis of toenails or fingernails.
AB  - BACKGROUND: Current studies have demonstrated the efficacy and safety of laser
      intervention in the treatment of onychomycosis. The objective of this study was
      to compare the efficacy of long-pulsed Nd:YAG 1064 nm laser for treatment of
      toenails onychomycosis with fingernails onychomycosis. METHODS: One hundred and
      twelve affected fingernails or toenails in 37 patients with onychomycosis were
      randomized into Group 1 (22 patients with 50 affected fingernails) and Group 2
      (15 patients with 62 affected toenails). These patients were further classified
      into three subgroups (Grade II, III, and IV) according to Scoring Clinical Index
      of Onychomycosis. All the affected nails were treated with long-pulse Nd:YAG 1064
      nm laser intervention, once weekly, for continuous weeks, and were followed up
      for 24 weeks. RESULTS: The response rates at weeks 8, 16, and 24 were 0, 0 and
      52%, respectively, for Group 1, and 10, 32 and 71% for Group 2. The inter-group
      difference in efficacy was statistically significant (P<0.05). Even in the same
      subgroup, the response rate of Group 2 was higher than that of Group 1.
      CONCLUSIONS: The efficacy of long-pulsed Nd:YAG 1064 nm laser intervention
      against affected toenails is superior to that against fingernails. It is also
      effective for treatment of onychomycosis with different severity.

PMID- 25607563
TI  - A randomized controlled clinical study to evaluate the effectiveness of an active
      moisturizing lotion with colloidal oatmeal skin protectant versus its vehicle for
      the relief of xerosis.
AB  - Xerosis is a common skin condition, occurring most often in the winter and in low
      relative humidity, which results in loss of moisture, cracking, and desquamation.
      Many emollient creams and lotions are available for use as preventive
      moisturizers. However, few controlled experiments have been published comparing
      the efficacy of active moisturizing products versus the vehicle used to deliver
      the products to the skin. Therefore, we conducted this randomized, double-blind,
      controlled clinical study to objectively compare a commercially available
      moisturizing product against its own vehicle. The active colloidal oatmeal
      moisturizer used in this study showed significant benefits versus its vehicle
      control in several dermatological parameters used to measure skin dryness.

PMID- 25607564
TI  - Use of multispectral digital skin lesion analysis for evaluation of nevi in
      children.
AB  - OBJECTIVE: We determine if the use of Multispectral Digital Skin Lesion Analysis
      for the evaluation of nevi in children and possible detection of malignancies.
      EVIDENCE REVIEW: Evidence gathered from a pivotal study involving 1,383 patients
      with 1,831-pigmented lesions. The isolated use of the pediatric population within
      this study was used to determine the specificity and sensitivity of such a device
      with comparison to a dermatologists evaluation. FINDINGS: For all lesions from
      the assessed pediatric population the biopsy ratio was equivalent for the
      Multispectral Digital Skin Lesion Analysis device as for the dermatologists when
      performing as independent reviewers. Furthermore analyzed data suggests that
      dermatologists who incorporate the Multispectral Digital Skin Lesion Analysis
      device perform better than they would independently or if they were to follow the
      device blindly without incorporating their own judgment. CONCLUSION AND
      RELEVANCE: An approach that integrates automated imaging technology like the
      Multispectral Digital Skin Lesion Analysis device, along with another diagnostic
      aid, with the end result being cost-effective, easy to use by even non-experts
      and comforting for the pediatric patient is likely to compete to be the new gold
      standard in successful early diagnosis and management of melanoma.

PMID- 25607565
TI  - Successful medical treatment of a severe reaction to red tattoo pigment.
AB  - Tattoo allergies are often eczematous skin rashes that can be complicated by
      ulceration and infection. These allergies are difficult to resolve, sometimes
      requiring surgical or laser intervention, with varying success. Here we present a
      case of a 29-year-old woman with a serious skin allergic reaction to red tattoo
      ink that ulcerated and became secondarily infected. The patient expressed a
      desire to have the tattoo allergic reaction treated while preserving the cosmetic
      appearance of her tattoo for sentimental reasons. This case is being presented to
      provide an effective treatment algorithm for managing allergic tattoo reactions
      with ulceration and co-infection, while preserving the aesthetic integrity of the
      tattoo.

PMID- 25607566
TI  - Metastatic squamous cell carcinoma presenting as an erythematous nodule in a man
      with lung adenocarcinoma.
AB  - Skin metastases from visceral malignancies have been well documented in the
      literature, and may be the presenting sign of an occult internal malignancy. Lung
      cancer in particular is a relatively common cause of skin metastases, which are
      considered a poor prognostic sign. Rarely, patients with lung cancer develop a
      second primary lung cancer that may require a novel chemotherapeutic regimen. The
      frequency of second primary malignancies presenting with metastatic skin lesions
      is not documented in the literature. We present a case of a 50-year-old man with
      a history of metastatic lung adenocarcinoma who was referred for evaluation of a
      nodule overlying his right mandible, which had been progressively enlarging for
      two weeks. Biopsy demonstrated metastatic squamous cell carcinoma. Subsequent CT
      guided biopsy of a left retroperitoneal lymph node was conducted and notable for
      squamous cell carcinoma. Therefore, this patient's skin lesion was the presenting
      sign of a second primary visceral tumor, likely originating in the lung. We
      present this case to raise clinical awareness of the rare phenomenon that
      cutaneous metastasis may be the first sign of a visceral cancer, even in the
      setting of a previous distinct primary malignancy.

PMID- 25607567
TI  - An adipocitolitic aqueous micro-gelatinous solution for buffalo hump deformity
      reduction.
AB  - Buffalo hump is a manifestation of HIV related lipodistrophy, it is characterized
      by an enlargment of dorsocervical fat pad and is distressing for patients.
      Surgical correction until a few years ago was the only option for treatment,
      however in last years non surgical corrections was carried out with minimally
      invasive techniques. Authors report this case that describe a longer follow up of
      an already published study were this deformity was treated with the injection of
      an adipocitolitic aqueous micro-gelatinous solution and during all the follow up
      no relapse was observed.

PMID- 25607568
TI  - A variant of palpable migratory arciform erythema.
AB  - Palpable migratory arciform erythema is a T-cell pseudolymphoma with no well
      established treatment. The disease is rarely reported in the literature, perhaps
      because it is difficult to diagnose. We present a case of a variant of PMAE in a
      30-year-old healthy man with no history of medication use and erythematous to
      violaceous annular and arciform plaques on his face, scalp and trunk. This case
      is of particular significance because gene rearrangement studies and
      histopathologic findings are concerning for folliculotropic mycosis fungoides
      while the clinical course does not support this diagnosis. The authors' emphasize
      that clinical history is imperative for definitive diagnosis of palpable
      migratory arciform erythema as it can clinically and histopathologically resemble
      other cutaneous lymphocytic diseases.

PMID- 25607570
TI  - The critical role of intragap states in the energy transfer from gold
      nanoparticles to TiO2.
AB  - Cathodoluminescence spectroscopy is profitably exploited to study energy transfer
      mechanisms in Au and Pt/black TiO2 heterostructures. While Pt nanoparticles
      absorb light in the UV region, Au nanoparticles absorb light by surface plasmon
      resonance and interband transitions, both of them occurring in the visible
      region. The intra-bandgap states (oxygen vacancies) of black TiO2 play a key role
      in promoting both hot electron transfer and plasmonic resonant energy transfer
      from Au nanoparticles to the TiO2 semiconductor with a consequent photocatalytic
      H2 production increase. An innovative criterion is introduced for the design of
      plasmonic composites with increased efficiency under visible light. 

PMID- 25607569
TI  - Ferrate(VI)-prompted removal of metals in aqueous media: mechanistic delineation
      of enhanced efficiency via metal entrenchment in magnetic oxides.
AB  - The removal efficiency of heavy metal ions (cadmium(II), Cd(II); cobalt(II),
      Co(II); nickel(II), Ni(II); copper(II), Cu(II)) by potassium ferrate(VI) (K2FeO4,
      Fe(VI)) was studied as a function of added amount of Fe(VI) (or Fe) and varying
      pH. At pH = 6.6, the effective removal of Co(II), Ni(II), and Cu(II) from water
      was observed at a low Fe-to-heavy metal ion ratio (Fe/M(II) = 2:1) while a
      removal efficiency of 70% was seen for Cd(II) ions at a high Fe/Cd(II) weight
      ratio of 15:1. The role of ionic radius and metal valence state was explored by
      conducting similar removal experiments using Al(III) ions. The unique combination
      of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), in-field
      Mossbauer spectroscopy, and magnetization measurements enabled the delineation of
      several distinct mechanisms for the Fe(VI)-prompted removal of metal ions. Under
      a Fe/M weight ratio of 5:1, Co(II), Ni(II), and Cu(II) were removed by the
      formation of MFe2O4 spinel phase and partially through their structural
      incorporation into octahedral positions of gamma-Fe2O3 (maghemite) nanoparticles.
      In comparison, smaller sized Al(III) ions got incorporated easily into the
      tetrahedral positions of gamma-Fe2O3 nanoparticles. In contrast, Cd(II) ions
      either did not form the spinel ferrite structure or were not incorporated into
      the lattic of iron(III) oxide phase due to the distinct electronic structure and
      ionic radius. Environmentally friendly removal of heavy metal ions at a much
      smaller dosage of Fe than those of commonly applied iron-containing coagulants
      and the formation of ferrimagnetic species preventing metal ions leaching back
      into the environment and allowing their magnetic separation are highlighted. 

PMID- 25607572
TI  - Severe Illness in Children Exposed to Natural Measles after Prior Vaccination
      against the Disease: A Report of Six Cases.
AB  - Abstract Six similar cases of moderate to severe illness after exposure to
      natural measles in children previously vaccinated against the disease are
      described. It is suggested that an Arthus-type antigen-antibody reaction is
      responsible for the clinical features observed. There is evidence that
      inactivated measles vaccine may be the causative factor. 

PMID- 25607573
TI  - Atypical measles after vaccination with killed vaccine.
AB  - Abstract Two cases are presented with diseases considered to be atypical measles
      as described by Fulginiti and Kempe. Two siblings, 8 and 9 years old, received
      measles vaccine in 1963 according to a schedule of 2 injections of killed vaccine
      1 month apart followed by 1 injection of live vaccine. In 1967 they contracted
      natural measles infection and developed a serious illness with high fever,
      exanthem, pneumonia and prostration. The patients recovered within 2 weeks. One
      patient has persistent infiltration in his left lung as revealed by X-ray
      examination. The diagnoses were substantiated epidemiologically and confirmed
      serologically. 

PMID- 25607574
TI  - Presence and persistence of australia antigen in patients with liver disorders.
AB  - Abstract Patients with suspected disease involving the liver and seen at a
      department for infectious diseases were examined routinely for Au-antigen. Of 344
      patients examined, 259 were found to have biochemical evidence of liver
      affection. Acute hepatitis was diagnosed in 129, including 65 with serum
      hepatitis, 18 with infectious hepatitis and 46 with sporadic hepatitis. 62
      patients had Au-antigen and 60 of them belonged to the group acute hepatitis. 69%
      of the patients with serum hepatitis and 28% of those with sporadic hepatitis
      were Au-antigen positive. Most of the patients harboured the antigen only
      temporarily. It was demonstrated up to 2-7 weeks after anamnestic onset. In 5
      patients Au-antigen in the serum persisted for 5-15 months; histologic
      examination of biopsy specimen showed signs of chronic liver disease in 4, only
      mild changes in 1. Only 3 patients had antibodies in the serum; all of them had
      been exposed to antigen for a long time. In one patient with arthritis Au-antigen
      was repeatedly demonstrated in both serum and joint exudate. 

PMID- 25607575
TI  - Hospital staphylococci in helsinki.
AB  - Abstract A total of 812 nasal swabs taken from the staff at 3 Helsinki city
      hospitals were examined. The carrier rate was 26%. Coagulase-positive
      staphylococci resistant to methicillin occurred in one hospital in 3%. They were
      multiple resistant. Strains belonging to phage group III dominated, accounting
      for 35%. Staphylococci of types 83A and 53/83A totalled 9% and those of type 6557
      7%. 

PMID- 25607576
TI  - Isolation of L-forms reverting to Staphylococcus aureus from pus of patients with
      staphylococcal infections: a study on 31 cases of staphylococcal infections
      treated with antibiotics.
AB  - Abstract The results of regularly performed cultures with the aim of isolating L
      forms from pus from 31 patients treated with antibiotics for staphylococcal
      infections are presented. In 3 cases growth of L-forms of Staphylococcus aureus
      was obtained on penicillin-free media. These patients had not been treated with
      cell wall affecting antibiotics for 2 weeks or more prior to the isolation of
      Informs. 

PMID- 25607577
TI  - Distribution of diplococcus pneumoniae types in acute otitis media in children
      and influence of the types on the clinical course in penicillin v therapy.
AB  - Abstract Pneumococci isolated from the ear exudate in 245 children under 10 years
      of age afflicted with acute otitis media were typed. Types 3, 6, 14, 18, 19 and
      23 were found in 80% of the cases. In the remaining cases, 15 other types were
      found. Five strains were not typable with the antisera used. Types 14 and 23 were
      found twice as often in the age group 0-3 years as in the higher age groups,
      whereas the opposite was true for type 3. The relapse frequency was highest after
      types 14 and 19 infections. The frequency of residual secretory otitis was
      highest after type 14 infections. Types 19 and 23 were never found in infections
      followed by secretory otitis. Patients with type 14 infections, healed or
      unhealed, showed the same blood group distribution within the ABO and Lewis
      systems as a normal Swedish population. Penicillin V therapy failed to eliminate
      the pneumococcal strain from the nasopharynx in 40% of consecutive cases of
      otitis media. Relapse after penicillin-treated pneumococcal otitis is to be
      regarded as a new complication of the primary infection and not as a reinfection
      from the environment. 

PMID- 25607578
TI  - Benign gonococcemia with skin lesions and arthritis.
AB  - Abstract An account is given of 16 cases of benign gonococcemia during the period
      Dec. 1, 1967 to Oct. 31, 1969. 15 patients were women, 1 man, and the average age
      was 29 years. The typical clinical picture consisted of fever, joint affection
      combined with a vesiculopapular, frequently hemorrhagic exanthema and genital
      gonococcal infection with usually slight or no symptoms and a good general
      condition throughout. Neisseria gonorrhoeae was isolated from the blood in 1
      case. Positive cultures were more frequently obtained from the genital and anal
      mucous membranes. With the fluorescent antibody technique gonococci were
      demonstrated from an efflorescence of 1 patient. Serological response was
      demonstrated in 8 patients. All cases had an unequivocal clinical picture.
      Penicillin resistance did not occur, but a reduction in sensitivity was noted in
      1 case. Treatment had prompt effect, but spontaneous healing was also seen. No
      complications or relapses were noted. 

PMID- 25607580
TI  - Urinary tract pathogens-sensitivity to trimethoprim/sulphamethoxazole.
AB  - Abstract The sensitivity to sulphamethizole, sulphamethoxazole (SM), trimethoprim
      (TMP) and the combination SM/TMP of freshly isolated urinary tract pathogens from
      hospital patients was studied. Out of 798 strains tested primarily, 47% were
      found to be fully sensitive to sulphamethizole (tablet method), and 81% fully
      sensitive to the SM/TMP combination (disk method). Out of 423 strains with
      reduced sensitivity to sulphamethizole, 65% were fully sensitive to SM/TMP. Out
      of 391 strains tested secondarily (disk method), 39% were fully sensitive to SM,
      68% fully sensitive to TMP, and 91% to SM/TMP. Of 283 strains presenting a
      reduced sensitivity to SM, 85% were fully sensitive to SM/TMP. In both series the
      isolated Streptococcus faecalis strains were highly resistant to sulphamethizole
      and SM, but presented a very high degree of sensitivity to TMP and SM/TMP. In
      contrast, nearly all isolated Pseudomonas aeruginosa strains were found to be
      resistant both to sulphonamides, TMP and SM/TMP. Of the 18 Staphylococcus aureus
      strains tested secondarily, 10 out of 12 multiresistant strains were fully
      sensitive to TMP. Synergy between SM and TMP could be demonstrated in 61% of the
      391 strains tested secondarily. The synergic effect depended on the degree of
      sensitivity to SM. 

PMID- 25607579
TI  - Bactericidal activity in sera from carriers of sulphonamide-resistant
      meningococci.
AB  - Abstract During the winter 1969 a small epidemic of meningococcal meningitis
      occurred in a naval training centre in Norway. After sulphonamide prophylaxis
      most of the meningococcal strains isolated from throat cultures from the recruits
      were resistant to sulphonamides (8, 9). Serological studies were undertaken in 43
      of the recruits, of whom 72% were found to be carriers of meningococci on at
      least one occasion. All these isolated strains were resistant to sulphonamides.
      In paired serum specimens, taken at the beginning of the epidemic and 6 weeks
      later, no increase in bactericidal antibodies against 4 meningococcal test
      strains belonging to the serogroups A, B, C, and Y was demonstrated. Against
      meningococcal strains isolated from the recruits themselves, however, a
      significant rise in titre was found, indicating that the recruits had been
      infected at about the same time as the first serum specimen was taken. In 26
      members of the permanent staff, 2 of them carriers of meningococci, the
      bactericidal titres were about equal to those in the recruits. Thus, the lower
      carrier rate in the permanent staff does not seem to be due to increased
      bactericidal potency of the serum. 

PMID- 25607581
TI  - Short-term treatment of urinary tract infections with
      trimethoprim/sulphamethoxazole: a clinical and bacteriological study.
AB  - Abstract The clinical effects of treatment with a trimethoprim (TMP)
      sulphamethoxazole (SM) combination were studied in 40 patients with urinary tract
      infection. The indication for treatment was symptoms of urinary tract infection
      with > 10(5) colonies per ml of urine. The dosage was 160 mg of TMP and 800 mg of
      SM administered orally twice daily for 10 days. The bacteriological in vitro
      examination revealed synergic effect of the two agents on 30 out of 55 bacterial
      strains (55%). Out of 32 strains which were resistant or slightly sensitive to
      SM, synergy was revealed in 14 instances (44%). Development of resistance to TMP
      was seen in one case. In 20 patients with non-complicated urinary tract
      infections, sterile urine was found 3 and 14 days after termination of treatment
      in 100% and 89%, respectively. In one case there was recurrence, and in one case
      reinfection occurred. In 20 patients with complicated urinary tract infections,
      sterile urine was found 3 and 14 days after termination of treatment in 80% and
      55%, respectively. In 4 cases infection recurred, and in 5 cases the treatment
      had no effect. Side effects were seen in 3 patients; one case of exanthem, one of
      nausea, and one of leucopenia. In one case treatment had to be withdrawn because
      of exanthem, in another because of nausea. 

PMID- 25607582
TI  - Recrudescent typhus: fluctuations in titers of complement-fixing and
      microagglutinating antibodies to rickettsia prowazeki in persons with a history
      of epidemic typhus.
AB  - Abstract A study on recrudescent typhus was conducted among 294 volunteers most
      of whom had contracted typhus in Eastern Europe and who immigrated to Israel
      after the Second World War. The main aim of the study was to determine whether
      persons, once infected, might subsequently suffer relapses without clinical signs
      which could presumably serve as sources of the microorganism in the interepidemic
      period and might be responsible for the initiation of new epidemics. The
      selection of volunteers was based on the reliability of their histories and on
      the absence of murine typhus in their present environment. Those under study were
      interviewed at regular 2-3 months' intervals during which blood samples were
      taken from them. Six blood samples were obtained from 262 individuals and at
      least 3 samples from the rest. Complement-fixation and microagglutination tests
      were carried out in order to establish the presence of antibodies specific for
      epidemic typhus. In 12% of the volunteers no demonstrable antibodies were found,
      while 67% considered to have such antibodies showed no significant titer
      fluctuations. However, 21% of the volunteers exhibited 4- to 8-fold fluctuations
      in titer in at least one of the tests used-a result which suggests the
      possibility of serological relapse. 

PMID- 25607583
TI  - Contamination of smears with "sergentella spiroides".
AB  - Abstract "Sergentella spiroides" is a filamentous fungal spore which can
      incidentally contaminate smears. In Romanowsky stainings the spores are
      confusingly like microfilariae and it is important to recognize the phenomenon to
      avoid diagnostic mistakes. 

PMID- 25607584
TI  - Wissler's Syndrome Associated with Parainfluenza 2 Infection.
AB  - Abstract A 9-year-old boy fell ill with respiratory symptoms and high fever,
      followed after a day or so by acute pleuritis. A classical Wissler's syndrome
      developed with altogether 3 attacks of high fever within the course of a month,
      various forms of exanthema on 2 occasions, arthritis in knee-joint, leucocytosis
      with eosinophilia attaining an extreme degree, and a high erythrocyte
      sedimentation rate. Blood cultures were negative; and, through extensive
      bacteriological tests and serological reactions, infections with various
      bacteria, mycoplasma, psittacosis agent and ordinary respiratory virus could be
      excluded with the exception of parainfluenza 2, for which infection there was
      clear serological evidence. Urinary findings with abundance of inclusion-bearing
      cells and occurrence of multinuclear giant cells may be considered to confirm
      this diagnosis. Pulmonary infiltrates, appearing after the acute pleuritis had
      receded, were probably due to small primary bronchopneumonias caused by
      parainfluenza 2. Infiltrates appearing in the subsequent course without clinical
      symptoms are classified, on the other hand, as eosinophil pulmonary infiltrates.
      These, as well as the primary pleuritis, must be regarded as subsymptoms of
      Wissler's syndrome. Aetiologically, a bacterial cause has been sought for
      earlier. The present case, however, shows that Wissler's syndrome may be brought
      on by a virus infection. The clinical picture may possibly reflect an individual
      reaction of an allergic nature to various infections, both bacteriological and
      virological. 

PMID- 25607585
TI  - Fatal varicella pneumonia.
AB  - Abstract A case of fatal varicella pneumonia in a 37-year-old woman is described.
      The clinical diagnosis was supported by the post-mortem examination which
      revealed extensive involvement of the lungs, skin and liver. Varicella virus was
      isolated from vesicular fluid and fluid obtained at lung puncture after death. No
      predisposing factor was found that could explain the fatal outcome of the
      infection. 

PMID- 25607586
TI  - N-confused porphyrin tautomers: lessons from density functional theory.
AB  - Using first-principle calculations, we characterize the properties of N-confused
      porphyrins (NCP), with a focus on the differences between the 2H and 3H
      tautomers. We find that NCP-3H is almost as strongly aromatic as porphyrin, and
      about twice as aromatic, i.e., remarkably more stable, than NCP-2H, due to the
      less efficient pi-conjugation in the latter form. The deprotonation of the NH
      group at the external side of the inverted ring of NCP-2H, adds a lone pair to
      the pi-system, which restores a strong aromaticity, while methylation has no
      significant effect. Investigating the impact of solvation using a continuum
      model, we find quite stable solvation energies with a relative dielectric
      constant, epsilonr, in the 5-40 range, for both tautomers. NCP-3H presents a
      slightly lower energy than its NCP-2H counterpart in all solvents. However, the
      energy differences between the two species are of the order of the error margin
      of the method, hence too small to discuss the experimentally observed
      stabilization of NCP-3H in dichloromethane (DCM, a poorly polar solvent) and NCP
      2H in N,N-dimethylformamide (DMF, a strongly polar solvent) or to extract the
      population ratios between the two forms in the different solvents. Therefore, the
      vibronic absorption spectra are also investigated in an effort to rationalize the
      complex absorption profiles of these NCP derivatives. We find very distinct
      spectra for the 2H and 3H forms in DMF and DCM, respectively, each fairly
      reproducing the experiment. We also find that, in the same solvent, the two
      species exhibit very different signatures, which allows us to conclude that the
      2H and 3H tautomers are largely dominant in DMF and DCM, respectively.
      Interestingly, the vibrational motions that strongly participate in the shoulder
      of the Soret band and the multiple maxima of the Q-bands largely differ in the
      two tautomers. 

PMID- 25607587
TI  - The paradox of impossible beauty: body changes and beauty practices in aging
      women.
AB  - The aim of this article is to describe and understand the experience of aesthetic
      body changes in women between 65 and 75 years old. To approach the issue, 29 in
      depth interviews were conducted in Marseille in 2011. Following a brief review of
      contemporary Western aesthetics, we will examine the marks of time women perceive
      as stigmatizing and analyze beauty practices that aim to conceal or repair them.
      The last part of this article will be devoted to the experience of the aesthetic
      body and in particular show how aging can paradoxically have a beneficial effect
      on some women. 

PMID- 25607588
TI  - Papilla Formation in Response to Computer-Assisted Implant Surgery and Immediate
      Restoration.
AB  - This retrospective analysis was undertaken to evaluate the effect of immediate
      implant restoration using a computer-assisted technique in partially edentulous
      sites on interimplant and intertooth bone level stability and papilla formation.
      Nine partially edentulous patients received a total of 23 implants that supported
      immediately placed implant restorations. Planning was accomplished using a
      radiographic guide, which allowed visualization of the emergence profile from the
      platform of the implant to the cervical of the planned restoration. Guided
      implants were placed according to the manufacturer's instructions, and
      restorations were screw retained directly to the implant. Multiple implants were
      splinted at surgery with autopolymerizing resin. Measurements were made at a mean
      of 545 days (range 288-958) postoperatively on the basis of radiographs and
      photographs. Measures were: (1) distance from bone crest to platform, (2) bone
      crest to contact point, (3) interimplant distance at the outer diameter of the
      platform, and (4) papilla from highest point to a reference line. At follow-up
      time, the bone ridge was located higher than the implant platform (mean 0.57 mm)
      compared to implants whose interimplant distance was less than 3 mm (mean 0.27
      mm). Mean increase of the bone level between insertion and approximate 1-year
      follow-up was 0.047 mm. The mean distance from the contact point to bone was
      2.39/3.93 mm postoperatively, resulting in 91/71% papilla fill between implants
      and between implant and adjacent tooth, respectively. Computer-assisted surgery
      with the preplanned immediate restoration seems to be an effective method to
      minimize bone loss at the implant platform resulting in support for papilla. 

PMID- 25607589
TI  - Spatial atmospheric atomic layer deposition of InxGayZnzO for thin film
      transistors.
AB  - We have investigated the nucleation and growth of InGaZnO thin films by spatial
      atmospheric atomic layer deposition. Diethyl zinc (DEZ), trimethyl indium (TMIn),
      triethyl gallium (TEGa), and water were used as Zn, In, Ga and oxygen precursors,
      respectively. The vaporized metal precursors have been coinjected in the reactor.
      The metal composition of InGaZnO has been controlled by varying the TMIn or TEGa
      flow to the reactor, for a given DEZ flow and exposure time. The morphology of
      the films changes from polycrystalline, for ZnO and In-doped ZnO, to amorphous
      for In-rich IZO and InGaZnO. The use of these films as the active channel in TFTs
      has been demonstrated and the influence of In and Ga cations on the electrical
      characteristics of the TFTs has been studied. 

PMID- 25607590
TI  - The fluid events model: Predicting continuous task action change.
AB  - The fluid events model is a behavioural model aimed at predicting the likelihood
      that people will change their actions in ongoing, interactive events. From this
      view, not only are people responding to aspects of the environment, but they are
      also basing responses on prior experiences. The fluid events model is an attempt
      to predict the likelihood that people will shift the type of actions taken within
      an event on a trial-by-trial basis, taking into account both event structure and
      experience-based factors. The event-structure factors are: (a) changes in event
      structure, (b) suitability of the current action to the event, and (c) time on
      task. The experience-based factors are: (a) whether a person has recently shifted
      actions, (b) how often a person has shifted actions, (c) whether there has been a
      dip in performance, and (d) a person's propensity to switch actions within the
      current task. The model was assessed using data from a series of tasks in which a
      person was producing responses to events. These were two stimulus-driven figure
      drawing studies, a conceptually driven decision-making study, and a probability
      matching study using a standard laboratory task. This analysis predicted trial-by
      trial action switching in a person-independent manner with an average accuracy of
      70%, which reflects a 34% improvement above chance. In addition, correlations
      between overall switch rates and actual switch rates were remarkably high (mean r
      = .98). The experience-based factors played a more major role than the event
      structure factors, but this might be attributable to the nature of the tasks. 

PMID- 25607591
TI  - New DEA rules expand options for controlled substance disposal.
AB  - Prescription drug abuse and overdose are rapidly growing problems in the United
      States. The United States federal Disposal of Controlled Substances Rule became
      effective 9 October 2014, implementing the Secure and Responsible Drug Disposal
      Act of 2010 (Disposal Act). These regulations target escalating prescription drug
      misuse by reducing accumulation of unused controlled substances that may be
      abused, diverted or accidentally ingested. Clinical areas that can now
      participate in collecting unused controlled substances include retail pharmacies,
      hospitals or clinics with an onsite pharmacy, and narcotic treatment programs.
      Collection methods include placing a controlled substance collection receptacle
      or instituting a mail-back program. Because prompt onsite destruction of
      collected items is required of mail-back programs, collection receptacles are
      more likely to be used in clinical areas. Retail pharmacies and hospitals or
      clinics with an onsite pharmacy may also place and maintain collection
      receptacles at long-term care facilities. The Act and Rule are intended to
      increase controlled substance disposal methods and expand local involvement in
      collection of unused controlled substances. Potential barriers to participating
      in controlled substance collection include acquisition of suitable collection
      receptacles and liners, lack of available space meeting the necessary criteria,
      lack of employee time for verification and inventory requirements, and program
      costs. 

PMID- 25607592
TI  - Disentangling natural and anthropogenic sources of atmospheric sulfur in an
      industrial region using biomonitors.
AB  - Despite reductions in atmospheric sulfur (S) concentrations due to abatement
      policies in some countries, modeling the dispersion of this pollutant and
      disentangling anthropogenic sources from natural ones is still of great concern.
      Lichens have been used as biomonitors of the impacts of S for over 40 years, but
      their potential as source-tracers of specific sources, including natural ones,
      remains unexplored. In fact, few attempts have been made to try to distinguish
      and spatially model different sources of S using lichens. We have measured S
      concentrations and isotopic values in lichens within an industrial coastal region
      where different sources of S, natural and anthropogenic, interplay. We detected a
      prevailing influence of natural sea-originated S that mixed with anthropogenic
      sources of S. We were then able to disentangle the sources of S, by removing the
      ocean influence on S isotopic values, enabling us to model the impact of
      different anthropogenic sources on S deposition and highlighting the potential
      use of lichens to evaluate the weight of different types of anthropogenic
      sources. 

PMID- 25607593
TI  - Treating the sequelae of postoperative meningioma and traumatic brain injury: a
      case of implementation of craniosacral therapy in integrative inpatient care.
AB  - BACKGROUND: Craniosacral therapy (CST) is a commonly used but under-researched
      therapeutic approach. This case study explores the implementation of CST in the
      integrative inpatient treatment of sequelae of postoperative meningioma and
      traumatic brain injury. CASE: A 50-year-old woman was admitted for 2 weeks of
      integrative inpatient treatment following meningioma resection and traumatic
      brain injury. In addition to the integrative treatment approach, which included
      conventional as well as complementary and alternative medicine, she received five
      sessions of CST for refractory headaches, vertigo, and cervicobrachial syndrome
      during this time. At discharge, the reported intensity of her headaches on a 10
      cm visual analogue scale decreased from 6-9 cm to 2-4 cm and her level of vertigo
      decreased from 6-10 cm to 2 cm. Her cervical mobility and muscle tension, sleep
      quality, and general well-being also improved. The attending physicians saw CST
      as having contributed greatly to this improvement alongside use of phytotherapy
      and hyperthermia. CONCLUSION: Implementation of CST in integrative inpatient care
      could benefit patients with headache and vertigo from intracranial injuries.

PMID- 25607594
TI  - The effect of incentive spirometry on postoperative pulmonary function following
      laparotomy: a randomized clinical trial.
AB  - IMPORTANCE: Changes in pulmonary dynamics following laparotomy are well
      documented. Deep breathing exercises, with or without incentive spirometry, may
      help counteract postoperative decreased vital capacity; however, the evidence for
      the role of incentive spirometry in the prevention of postoperative atelectasis
      is inconclusive. Furthermore, data are scarce regarding the prevention of
      postoperative atelectasis in sub-Saharan Africa. OBJECTIVE: To determine the
      effect of the use of incentive spirometry on pulmonary function following
      exploratory laparotomy as measured by forced vital capacity (FVC). DESIGN,
      SETTING, AND PARTICIPANTS: This was a single-center, randomized clinical trial
      performed at Kamuzu Central Hospital, Lilongwe, Malawi. Study participants were
      adult patients who underwent exploratory laparotomy and were randomized into the
      intervention or control groups (standard of care) from February 1 to November 30,
      2013. All patients received routine postoperative care, including instructions
      for deep breathing and early ambulation. We used bivariate analysis to compare
      outcomes between the intervention and control groups. INTERVENTION: Adult
      patients who underwent exploratory laparotomy participated in postoperative deep
      breathing exercises. Patients in the intervention group received incentive
      spirometers. MAIN OUTCOMES AND MEASURES: We assessed pulmonary function using a
      peak flow meter to measure FVC in both groups of patients. Secondary outcomes,
      such as hospital length of stay and mortality, were obtained from the medical
      records. RESULTS: A total of 150 patients were randomized (75 in each arm). The
      median age in the intervention and control groups was 35 years (interquartile
      range, 28-53 years) and 33 years (interquartile range, 23-46 years),
      respectively. Men predominated in both groups, and most patients underwent
      emergency procedures (78.7% in the intervention group and 84.0% in the control
      group). Mean initial FVC did not differ significantly between the intervention
      and control groups (0.92 and 0.90 L, respectively; P=.82 [95% CI, 0.52-2.29]).
      Although patients in the intervention group tended to have higher final FVC
      measurements, the change between the first and last measured FVC was not
      statistically significant (0.29 and 0.25 L, respectively; P=.68 [95% CI, 0.65
      1.95]). Likewise, hospital length of stay did not differ significantly between
      groups. Overall postoperative mortality was 6.0%, with a higher mortality rate in
      the control group compared with the intervention group (10.7% and 1.3%,
      respectively; P=.02 [95% CI, 0.01-0.92]). CONCLUSIONS AND RELEVANCE: Education
      and provision of incentive spirometry for unmonitored patient use does not result
      in statistically significant improvement in pulmonary dynamics following
      laparotomy. We would not recommend the addition of incentive spirometry to the
      current standard of care in this resource-constrained environment. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01789177.

PMID- 25607596
TI  - Topical application of sphingosine 1-phosphate receptor 1 prolongs corneal graft
      survival in mice.
AB  - The present study aimed to investigate the effects of topical application of
      sphingosine 1-phosphate receptor 1 (S1P1) on allogeneic corneal transplantation
      in mice. A total of 45 BALB/c mice received corneal grafts from C57BL/6 donors.
      The recipients were randomly divided into three groups and treated with eye drops
      containing 0.5% S1P1, 1% cyclosporine A or saline as a negative control. The
      serum levels of interleukin (IL)-2, IL-10, tumor growth factor (TGF)-beta1 and
      interferon (IFN)-gamma were measured by ELISA. The numbers of CD4+ T cell and T
      regulatory (Treg) cell phenotypes were measured by flow cytometry. The cytokine
      mRNA expression was analyzed by quantitative polymerase chain reaction. The
      results demonstrated that corneal graft survival was prolonged in the S1P1 group
      [mean survival time (MST), 24.11+/-1.58 days], and 1% cyclosporine A (MST, 25.0+/
      1.91 days) compared with the controls (MST, 13.44+/-0.48 days; P<0.01). S1P1 and
      cyclosporine A decreased CD4+ T-cell levels (P<0.05) in the peripheral blood
      compared with those of the controls. However, an increase of CD4+ T cells in the
      spleen was noted in the S1P1 group (P<0.05) and Treg cells were also increased in
      the cervical lymph nodes in the S1P1 group (P<0.01). TGF-beta1 mRNA transcription
      in the corneal grafts increased following treatment with S1P1 (P<0.05) and TGF
      beta1 in the serum following treatment with S1P1 also increased (P<0.01). In
      conclusion, S1P1 had a significant effect in corneal allograft rejection
      inhibition.

PMID- 25607595
TI  - Characterizing the transmission dynamics and control of ebola virus disease.
AB  - Carefully calibrated transmission models have the potential to guide public
      health officials on the nature and scale of the interventions required to control
      epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in
      Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant
      modeling approach to capture the distributions of the number of secondary cases
      that arise in the community and health care settings in the context of changing
      population behaviors and increasing hospital capacity. Their findings underscore
      the role of increasing the rate of safe burials and the fractions of infectious
      individuals who seek hospitalization together with hospital capacity to achieve
      epidemic control. However, further modeling efforts of EVD transmission and
      control in West Africa should utilize the spatial-temporal patterns of spread in
      the region by incorporating spatial heterogeneity in the transmission process.
      Detailed datasets are urgently needed to characterize temporal changes in
      population behaviors, contact networks at different spatial scales, population
      mobility patterns, adherence to infection control measures in hospital settings,
      and hospitalization and reporting rates. 

PMID- 25607597
TI  - Downregulation of SNAIL sensitizes hepatocellular carcinoma cells to TRAIL
      induced apoptosis by regulating the NF-kappaB pathway.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second
      most lethal cancer worldwide. Evidence has shown HCC cell resistance to TRAIL
      mediated apoptosis. In a previous study, we verified that silencing SNAIL
      downregulated the growth of HCC cells. In addition, the mechanism of resistance
      to TRAIL in HCC cells was connected with the activation of nuclear factor-kappaB
      (NF-kappaB). Thus, it was hypothesized that the downregultaion of SNAIL
      sensitizes HCC cells to TRAIL-induced apoptosis by regulating the NF-kappaB
      pathway. In the present study, the most effective lentiviral vectors carrying
      shRNA against SNAIL were selected and adenoviral vectors harboring TRAIL were
      constructed. The expression of SNAIL and TRAIL was detected by quantitative PCR
      and western blotting. HCC cell viability and apoptosis were assessed using an MTT
      assay and the Hoechst test. To determine how to sensitize HCC cells to TRAIL
      induced apoptosis after silencing SNAIL, p53 was assessed by western blot
      analysis. We also investigated the expression of Bcl-xL, cIAP2, survivin and Raf
      1 protein using western blot analysis and the apoptotic degree of HuH-7 cells was
      detected using the Hoechst test following the suppression of each gene, which was
      a possible molecular mechanism to sensitive TRAIL-induced apoptosis through the
      downregulation of SNAIL in HCC cells. Silencing SNAIL resulted in increased
      apoptosis by enhancing sensitization to TRAIL in all the HCC cells. Additionally,
      p53 protein was upregulated in HuH-7 cells. Expression of Bcl-xL, cIAP2, survivin
      and Raf-1 was downregulated following silencing of SNAIL, while down-regulation
      of any of the proteins contributed to SNAIL suppression enhancing HCC cell
      sensitivity to TRAIL-induced apoptosis, with the exception of cIAP2. The results
      demonstrated that silencing SNAIL can sensitize TRAIL-induced apoptosis in HCC
      cells by upregulating p53 protein and by regulating related genes of the NF
      kappaB pathway such as Bcl-xL, survivin and Raf-1.

PMID- 25607598
TI  - Suicide in a health maintenance organization population.

PMID- 25607599
TI  - Raman-activated cell sorting based on dielectrophoretic single-cell trap and
      release.
AB  - Raman-activated cell sorting (RACS) is a promising single-cell technology that
      holds several significant advantages, as RACS is label-free, information-rich,
      and potentially in situ. To date, the ability of the technique to identify single
      cells in a high-speed flow has been limited by inherent weakness of the
      spontaneous Raman signal. Here we present an alternative pause-and-sort RACS
      microfluidic system that combines positive dielectrophoresis (pDEP) for single
      cell trap and release with a solenoid-valve-suction-based switch for cell
      separation. This has allowed the integration of trapping, Raman identification,
      and automatic separation of individual cells in a high-speed flow. By exerting a
      periodical pDEP field, single cells were trapped, ordered, and positioned
      individually to the detection point for Raman measurement. As a proof-of-concept
      demonstration, a mixture of two cell strains containing carotenoid-producing
      yeast (9%) and non-carotenoid-producing Saccharomyces cerevisiae (91%) was
      sorted, which enriched the former to 73% on average and showed a fast Raman
      activated cell sorting at the subsecond level. 

PMID- 25607600
TI  - Smoking-related knowledge, attitude, social pressure, and environmental
      constraints among new undergraduates in Chongqing, China.
AB  - BACKGROUND: Smoking has resulted in numerous deaths in China. Data indicate that
      21% of college students in China are smokers. OBJECTIVE: This study aimed to
      examine the smoking-related behaviors of undergraduates, as influenced by
      knowledge, attitude, social pressure, and environmental constraints. METHOD: A
      convenience sampling of 412 fresh undergraduates from two universities in the
      University Town in Chongqing, China was recruited. Chi-square tests were used to
      compare the smoking-related variables between smokers and non-smokers. Moreover,
      logistic regression was used to examine the factors that associated with smoking
      status in undergraduates. RESULTS: Smokers and non-smokers differ in terms of
      knowledge, attitudes toward smoking, participation in tobacco promotional
      activities, and sources of social pressure. Logistic regression model identified
      that sex, living cost, five smoking-related attitudes of "Smoking is pleasurable,
      Smoking relaxes me, Smoking makes me look strong, Smoking is a waste of money,
      Smoking can help me study better", the social pressure "Smoking brings comfort
      during celebration", and the environmental constraints "How did you get your
      cigarettes in the past 30 days?" are significantly associated with smoking.
      CONCLUSIONS: The findings provide a better understanding of the epidemic of
      smoking among fresh undergraduates in Chongqing, China. This study provides more
      detailed consideration of the implications for the WHO Framework Convention on
      Tobacco Control (FCTC) policies, especially on restriction of retail sales
      outlets and tobacco promotion activities near universities in China.

PMID- 25607602
TI  - Local sustainability and gender ratio: evaluating the impacts of mining and
      tourism on sustainable development in Yunnan, China.
AB  - This study employed rapid evaluation methods to investigate how the leading
      industries of mining and tourism impact sustainability as manifest through
      social, economic and environmental dimensions in Yunnan, China. Within the social
      context, we also consider the differentiated impact on gender ratio-which is a
      salient feature of sustained development trajectories. Our results indicate that
      mining areas performed better than tourism areas in economic aspects but fell
      behind in social development, especially regarding the issue of gender balance.
      Conclusions on environmental status cannot be drawn due to a lack of data.  The
      results from the environmental indicators are mixed. Our study demonstrates that
      rapid evaluation using currently available data can provide a means of greater
      understanding regarding local sustainability and highlights areas that need
      attention from policy makers, agencies and academia. 

PMID- 25607601
TI  - Effects of horizontal acceleration on human visual acuity and stereopsis.
AB  - The effect of horizontal acceleration on human visual acuity and stereopsis is
      demonstrated in this study. Twenty participants (mean age 22.6 years) were
      enrolled in the experiment. Acceleration from two different directions was
      performed at the Taiwan High-Speed Rail Laboratory. Gx and Gy (< and >0.1 g) were
      produced on an accelerating platform where the subjects stood. The visual acuity
      and stereopsis of the right eye were measured before and during the acceleration.
      Acceleration <0.1 g in the X- or Y-axis did not affect dynamic vision and
      stereopsis. Vision decreased (mean from 0.02 logMAR to 0.25 logMAR) and
      stereopsis declined significantly (mean from 40 s to 60.2 s of arc) when Gx > 0.1
      g. Visual acuity worsened (mean from 0.02 logMAR to 0.19 logMAR) and poor
      stereopsis was noted (mean from 40 s to 50.2 s of arc) when Gy > 0.1 g. The
      effect of acceleration from the X-axis on the visual system was higher than that
      from the Y-axis. During acceleration, most subjects complained of ocular strain
      when reading. To our knowledge, this study is the first to report the exact
      levels of visual function loss during Gx and Gy. 

PMID- 25607603
TI  - Benzo[a]pyrene and Benzo[k]fluoranthene in some processed fish and fish products.
AB  - In this study, the concentration levels of the probable carcinogenic PAH
      fractions, benzo[a]pyrene (BaP) and benzo[k]fluoranthrene (BkF) in fillets of
      some processed fish species were investigated. Fish species comprising Merluccius
      poli (hake), Tyrsites atun (snoek), Seriola lalandi (yellow-tail) and Brama brama
      (angel fish) were bought in fish shops at Gordon's Bay, Western Cape, South
      Africa. The fish were gutted, filleted and prepared for edibility by frying,
      grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each
      homogenized fish sample, cleaned-up using solid phase extraction (SPE), and
      analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled
      with a Flame Ionization Detector (GC-FID). The sum of the two PAHs (?2PAH) i.e.,
      BaP and BkF ranged between 0.56 and 1.46 ug/kg, in all boiled, grilled and fried
      fish species. The fried fish extracts showed significantly higher (p < 0.05)
      abundance of ?2PAH, than grilled and boiled fish. Dietary safety and PAHs
      toxicity was also discussed. 

PMID- 25607604
TI  - Assessing metal exposures in a community near a cement plant in the Northeast
      U.S.
AB  - Cement production is a major source of metals and metalloids in the environment,
      while exposures to metals and metalloids may impact human health in the
      surrounding communities. We recruited 185 participants living in the vicinity of
      a cement plant in the northeast U.S., and measured the levels of aluminum (Al),
      arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), and selenium (Se) in blood
      and Hg in hair samples from them. A questionnaire was used to assess potential
      sources of Hg exposure. Multivariate regressions and spatial analyses were
      performed to evaluate the relative importance of different routes of exposures.
      The metal concentrations in blood or hair samples of our study participants were
      comparable to the U.S. general or regional population. Smoking contributed
      significantly to Cd and Pb exposures, and seafood consumption contributed
      significantly to Hg and As exposures, while variables related to the cement plant
      were not significantly associated with metal concentrations. Our results suggest
      that our study population was not at elevated health risk due to metal exposures,
      and that the contribution of the cement plant to metal exposures in the
      surrounding community was minimal. 

PMID- 25607605
TI  - Prevalence of virulence determinants and antimicrobial resistance among commensal
      Escherichia coli derived from dairy and beef cattle.
AB  - Cattle is a reservoir of potentially pathogenic E. coli, bacteria that can
      represent a significant threat to public health, hence it is crucial to monitor
      the prevalence of the genetic determinants of virulence and antimicrobial
      resistance among the E. coli population. The aim of this study was the analysis
      of the phylogenetic structure, distribution of virulence factors (VFs) and
      prevalence of antimicrobial resistance among E. coli isolated from two groups of
      healthy cattle: 50 cows housed in the conventional barn (147 isolates) and 42
      cows living on the ecological pasture (118 isolates). The phylogenetic analysis,
      identification of VFs and antimicrobial resistance genes were based on either
      multiplex or simplex PCR. The antimicrobial susceptibilities of E. coli were
      examined using the broth microdilution method. Two statistical approaches were
      used to analyse the results obtained for two groups of cattle. The relations
      between the dependent (VFs profiles, antibiotics) and the independent variables
      were described using the two models. The mixed logit model was used to
      characterise the prevalence of the analysed factors in the sets of isolates. The
      univariate logistic regression model was used to characterise the prevalence of
      these factors in particular animals. Given each model, the odds ratio (OR) and
      the 95% confidence interval for the population were estimated. The phylogroup B1
      was predominant among isolates from beef cattle, while the phylogroups A, B1 and
      D occurred with equal frequency among isolates from dairy cattle. The frequency
      of VFs-positive isolates was significantly higher among isolates from beef
      cattle. E. coli from dairy cattle revealed significantly higher resistance to
      antibiotics. Some of the tested resistance genes were present among isolates from
      dairy cattle. Our study showed that the habitat and diet may affect the genetic
      diversity of commensal E. coli in the cattle. The results suggest that the
      ecological pasture habitat is related to the increased spreading rate of the VFs,
      while the barn habitat is characterised by the higher levels of antimicrobial
      resistance among E. coli. 

PMID- 25607606
TI  - Risk communication concerning welding fumes for the primary preventive care of
      welding apprentices in southern Brazil.
AB  - This study's aim was to assess the perceptions of welding apprentices concerning
      welding fumes being associated with respiratory and cardiovascular disorders and
      assess the implementation of risk communication as a primary prevention tool in
      the welding training process. This quasi-experimental, non-randomized study with
      before-and-after design was conducted with 84 welding apprentices in Southern
      Brazil. Poisson Regression analysis was used. Relative Risk was the measure used
      with a 95% confidence interval and 5% (p <= 0.05) significance level. Significant
      association was found between perceptions of worsened symptoms of respiratory
      disorders caused by welding fumes and educational level (p = 0.049), the use of
      goggles to protect against ultraviolet rays (p = 0.023), and access to services
      in private health facilities without insurance coverage (p = 0.001). Apprentices
      younger than 25 years old were 4.9 times more likely to perceive worsened
      cardiovascular symptoms caused by welding fumes after risk communication (RR =
      4.91; CI 95%: 1.09 to 22.2). The conclusion is that risk communication as a
      primary preventive measure in continuing education processes implemented among
      apprentices, who are future welders, was efficacious. Thus, this study confirms
      that risk communication can be implemented as a primary prevention tool in
      welding apprenticeships. 

PMID- 25607607
TI  - PINK1- and PARK2-mediated local mitophagy in distal neuronal axons.
AB  - Mutations in the PINK1 and PARK2/PARKIN genes are associated with hereditary
      early onset Parkinson disease (PD), and in cell lines the corresponding gene
      products play a critical role in mitophagic clearance of damaged mitochondria. In
      neurons, however, where the extraordinary cellular shapes pose particular
      challenges for maintaining healthy mitochondria, the pathways of mitophagy are
      less well understood. Both the location at which mitophagy occurs and the
      involvement of PINK1 and PARK2 have been controversial. Here we review our recent
      study where we found that selective damage to a subset of axonal mitochondria
      causes them to be engulfed within autophagosomes and cleared locally within the
      axon without the need for transport back to the soma. We also found this process
      to be completely dependent on neuronal PINK1 and PARK2. 

PMID- 25607609
TI  - Vibronic structure in the far-UV electronic circular dichroism spectra of
      proteins.
AB  - The Franck-Condon effect is considered and the vibrational structure of the
      pinbpi* transition of the peptide backbone is incorporated into matrix method
      calculations of the electronic circular dichroism (CD) spectra of proteins in the
      far-ultraviolet. We employ the state-averaged CASPT2 method to calculate the
      ground and pinbpi* excited state geometries and frequencies of N-methylacetamide
      (NMA), which represents the peptide chromophore. The results of these
      calculations are used to incorporate vibronic levels of the excited states into
      the matrix method calculation. The CD spectra of a set of 49 proteins, comprising
      a range of structural types, are calculated to assess the influence of the
      vibrational structure. The calculated spectra of alpha-helical proteins are
      better resolved using the vibronic parameters and correlation between the
      experimental and the calculated intensity of less regular beta structure proteins
      improves over most wavelengths in the far-UV. No obvious improvement is observed
      in the calculated spectra of regular beta-sheet proteins. Our high-level ab
      initio calculations of the vibronic structure of the pinbpi* transition in NMA
      have provided some further insight into the physical origins of the nature of
      protein CD spectra in the far-UV. 

PMID- 25607608
TI  - A 24-month study evaluating the efficacy and safety of denosumab for the
      treatment of men with low bone mineral density: results from the ADAMO trial.
AB  - CONTEXT: One in 4 men in the United States aged >50 years will have an
      osteoporosis-related fracture. Fewer data are available on osteoporosis treatment
      in men than in women. OBJECTIVE: The purpose of this study was to evaluate
      denosumab therapy in men with low bone mineral density (BMD). DESIGN: This was a
      phase 3 study with 2 treatment periods: a previously reported 12-month double
      blind, placebo-controlled phase and a 12-month open-label phase. SETTING: This
      was a multicenter study conducted in North America and Europe. PARTICIPANTS: A
      total of 228 men entered the open-label phase and 219 completed the study.
      INTERVENTION: Men from the original denosumab (long-term) and placebo (crossover)
      groups received 60 mg of denosumab sc every 6 months. MAIN OUTCOME MEASURES: BMD,
      serum collagen type I C-telopeptide, and safety were measured. RESULTS: During
      the open-label phase, continued BMD increases occurred with long-term denosumab
      treatment (2.2% lumbar spine, 0.9% total hip, 1.3% femoral neck, 1.3% trochanter,
      and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of
      8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P < .01). The crossover group
      showed BMD gains after 12 months of denosumab treatment similar to those of the
      long-term denosumab group during the first treatment year. Significant reductions
      in serum collagen type I C-teleopeptide were observed after denosumab
      administration. Adverse event rates were similar between groups, and no new
      safety signals were identified. CONCLUSIONS: In men with low BMD, denosumab
      treatment for a second year continued to increase BMD, maintained reductions in
      bone resorption, and was well tolerated. BMD increased in men initiating
      denosumab during the second year. These effects were similar to those previously
      seen in postmenopausal women with osteoporosis and in men with prostate cancer
      receiving androgen deprivation therapy.

PMID- 25607611
TI  - Care a calling.

PMID- 25607610
TI  - Inhibitory effect of terpinen-4-ol on voltage-dependent potassium currents in rat
      small sensory neurons.
AB  - The biological and pharmacological activities of the terpenoid terpinen-4-ol (1),
      which include depressant effects in the central nervous system, are of potential
      therapeutic interest. In the present study, the effects of 1 on neuronal
      excitability and voltage-dependent K(+) currents in the somatic sensory system
      were investigated. Intact and dissociated neurons of rat dorsal root ganglia
      (DRG) were used for intracellular and patch-clamp recordings, respectively. In
      neurons of intact DRG, 1 caused concentration-dependent depolarization of the
      resting membrane potential and increased input resistance. 1 also inhibited
      action potentials (AP) and decreased AP parameters, with the exception of AP
      duration, which was increased. In dissociated DRG neurons, 1 partially blocked
      the total K(+) current in a concentration-dependent manner. 1 inhibited I(A),
      I(D), and I(K) with IC50 values of 3.2 +/- 03, 0.7 +/- 0.1, and 1.6 +/- 0.7 mM,
      respectively. 1 did not shift either the steady-state activation or inactivation
      curves of I(A), I(D), and I(K) but reduced the decay time course of I(A). The
      alterations in DRG reported here are consistent with the inhibition of K(+)
      currents and might partially explain the effect of 1 on excitable tissues.

PMID- 25607612
TI  - What's in the name? Care management ... more important than ever.

PMID- 25607613
TI  - Opportunities to improve pain management outcomes in total knee replacements:
      patient-centered care across the continuum.
AB  - Despite the importance of pain management to each patient's overall experience
      with a total knee replacement, opportunities to improve pain care exist. The
      authors target an unnecessarily fragmented pain management trajectory as one
      cause of variability in pain outcomes. They propose that a technology-enhanced
      patient-centered pain management continuum running from the preoperative through
      the recovery phase offers effective and efficient pain management. 

PMID- 25607615
TI  - Changing measures to evaluate changing bone.
AB  - Osteoporosis is a silent, progressive disease affecting millions of Americans,
      costing $23.5 billion annually (). Fragility fractures, painful and costly
      sequelae of osteoporosis, are frequently underdiagnosed and undertreated
      partially because of limited assessment measures. Currently, bone mineral density
      measured by dual-energy x-ray absorptiometry is the surrogate marker of bone
      health () but has shortcomings predicting fragility fractures. Bone turnover
      markers and magnetic resonance spectroscopy are promising techniques for earlier,
      more accurate assessment of bone physiology and structure. Bone turnover markers
      reflect the dynamic nature of living bone (), thus providing a more comprehensive
      picture of bone health. Magnetic resonance spectroscopy may hold predictive power
      in determining fast and slow bone mineral density losers (). The use of these
      tools may assist with diagnosis of osteoporosis, allowing earlier determination
      of the effectiveness of prescribed therapies to improve bone health. 

PMID- 25607617
TI  - Adolescent avulsion injuries of the pelvis: a case study and review of the
      literature.
AB  - Avulsion fractures of the pelvic apophyses are a result of repetitive strain
      injuries or sudden, forceful eccentric or concentric contractions of
      corresponding muscle groups in the leg. Using a case study approach, we present
      the clinical and radiological features, and management of a 14-year-old boy who
      presented to our hospital with an avulsion fracture of the anterior inferior
      iliac spine. The literature on the subject, along with the management of the
      condition, is reviewed and presented. A condition often treated nonoperatively,
      the focus of treatment is based on effective nursing and rehabilitation of the
      patient on an outpatient basis. Without this vital role, patients are at risk of
      unnecessary hospitalization that also has adverse socioeconomic effects. 

PMID- 25607619
TI  - Exploring New Zealand orthopaedic nurses' knowledge of osteoporosis.
AB  - BACKGROUND: Osteoporosis is a highly prevalent yet preventable disease. Nurses
      can play a major role in the prevention of osteoporosis and preventive treatment
      of patients who have had an osteoporotic fracture. PURPOSE: This study explored
      whether New Zealand orthopaedic nurses have the knowledge to provide osteoporosis
      prevention education, and also examined these nurses' perceptions of their role
      in the diagnosis and prevention of osteoporosis. METHODS: A questionnaire
      assessing osteoporosis knowledge was sent to a convenience sample of orthopaedic
      nurses. Data were analyzed quantitatively for the knowledge component, and
      qualitatively for the nurses' perception of their role, perceived barriers, and
      educational preferences. RESULTS AND CONCLUSION: Findings reveal that New Zealand
      orthopaedic nurses have inadequate osteoporosis knowledge and this is a barrier
      to educating patients regarding osteoporosis. Adherence to published
      recommendations for the management of osteoporosis has been inconsistent.
      Confusion about who should lead osteoporosis prevention is evident and it seems
      that nurses play a passive role.

PMID- 25607621
TI  - Symptom clusters, functional status, and quality of life in older adults with
      osteoarthritis.
AB  - BACKGROUND: One in two people may develop symptomatic knee osteoarthritis (OA) in
      their lifetime. Many OA sufferers have multiple symptoms, including pain,
      fatigue, and depressive symptoms. Determining whether symptom clusters exist
      among these older adults and what their effects are on outcomes such as quality
      of life (QOL) and functional status is essential to provide evidence-based
      geriatric healthcare. PURPOSE: The purposes of the secondary analyses were to
      explore symptoms that form clusters in older adults with OA of the knee and the
      effects of symptom clusters on their QOL and functional status. METHOD: A cross
      sectional, methodological exploration of existing data from a convenience sample
      (N = 75) of adults aged 50 years and older with OA of the knee was used.
      Hierarchical and k-means cluster analyses were used to identify symptom clusters.
      MANOVA was performed to test for joint differences in QOL and functional status.
      RESULTS: Two large clusters of pain, fatigue, and depressive symptoms were
      identified from the cluster, and significant relationships were found between
      symptom clusters and both QOL (p = .008) and functional status (p < .001).
      Conclusions about QOL or functional status differences were similar for
      alternative clustering strategies or numbers of symptom clusters in sensitivity
      analyses. CONCLUSION: The findings of this study provide a foundation for
      targeted interventions to improve QOL and functional status of older adults with
      OA of the knee.

PMID- 25607623
TI  - The relationship between nonsurgical pain and interference with activity in
      patients undergoing a total knee arthroplasty.
AB  - BACKGROUND: Patients with nonsurgical pain (NSP) after a total knee arthroplasty
      (TKA) report different patterns of pain interference than those without NSP.
      PURPOSE: This study explores the severity and ways in which NSP interferes with
      activities 48 hours and 6-7 weeks post surgery. ANALYSIS: Univariate and
      multivariate analyses were used. The mean score for intensity at 48 hours was
      1.78, and at 6-7 weeks it was 1.15. The mean score for interference with
      activities at 48 hours was 1.62 and at 6-7 weeks it was 0.91. Highest NSP pain
      interference at 48 hours was for "activity," "sleep," and "enjoyment of life." At
      6-7 weeks, the highest scores were for "activity," "sleep," and "walking." No
      significant differences were noted for age, race, education, or gender.
      IMPLICATIONS: Although rated "mild," this pain should be addressed. The NSP
      indicates a baseline of chronic and persistent pain, which is an opportunity to
      work with our patients to mitigate this pain. Total knee arthroplasty, a common
      and effective treatment for painful knee conditions attributed to various forms
      of arthritis, is known to be a painful surgical procedure. Two of the major
      concerns voiced by patients awaiting TKA are about postoperative pain management
      and rehabilitation efforts after the procedure (). Healthcare providers offer a
      range of methods and strategies to deal with postoperative TKA pain, yet to date
      no single method offers complete satisfaction (; ; ; ).

PMID- 25607624
TI  - Ultrasound and shockwave therapy for acute fractures in adults.

PMID- 25607625
TI  - Watch out for luxatio erecta of the shoulder.
AB  - Traumatic inferior dislocation of the shoulder (also termed "luxatio erecta") is
      a very rare injury. The correct diagnosis may be overlooked and results after
      reduction can often result in significant morbidity of the affected joint. It is
      described in a clinical case in which a male adult reported a luxatio erecta that
      was correctly diagnosed and reduced with uneventful recovery. Since it is a quite
      rare event in the emergency room, a careful review of the literature warned us
      about potential pitfalls in diagnosis and treatment of this peculiar injury. Our
      brief case report is intended to furnish educational images and stress the
      importance of a correct clinical and radiographic evaluation. 

PMID- 25607627
TI  - Sonographic and Doppler Sonographic Diagnosis of Posthemorrhagic Hydrocephalus.
AB  - Severe intracranial hemorrhages occur especially in very immature premature
      infants born with a gestational age under 28 weeks of gestation and a birth
      weight below 1000 g. Severe hemorrhages are often complicated by a post
      hemorrhagic hydrocephalus (PHH). PHH can be caused by a blockage of the cerebro
      spinal fluid pathways or by obliterative arachnoiditis of the posterior cranial
      fossa. Cerebral sonography can differentiate between both entities. In cases of
      obstruction of the cerebro-spinal fluid circulation the parts of the ventricular
      system infront of the obstruction are dilated. Color coded Doppler sonography can
      display the patency or obstruction of the physiologic constrictions of the
      ventricular system. Increased intracranial pressure can noninvasively be detected
      by spectral Doppler: The increase of the peak systolic flow velocity in the
      intracranial section of the internal carotid artery in comparison with the extra
      cranial part is an early indication of a raised intracranial pressure. The
      decrease of the end-diastolic flow velocity during fontanel compression is
      indicative of abolished cranial compliance and increased intracranial pressure.
      In the case of raised intracranial pressure diastolic amplitudes and end
      diastolic flow velocities are decreased and the resistive-indices are increased.

PMID- 25607628
TI  - CEUS Time Intensity Curves in the Differentiation Between Leydig Cell Carcinoma
      and Seminoma: A Multicenter Study.
AB  - PURPOSE: Ultrasound (US) is the main imaging technique in the assessment of
      testicular masses, as it has proved to be highly accurate in the visualization of
      these pathologies. Identification of a Leydig cell tumor is essential since the
      lesion is benign in 90% of cases. The aim of this multicenter study is to assess
      the effectiveness of contrast-enhanced ultrasound (CEUS) in differentiating
      Leydig cell tumors from seminoma using qualitative and quantitative features.
      MATERIALS AND METHODS: From February 2011 to December 2013, 31 patients (mean
      age: 34 years; range: 25 - 52) were recruited for this prospective study. Three
      of them were monorchid. Therefore, a total of 59 testicles were assessed. All
      patients underwent grayscale US, color Doppler ultrasound (CDUS), CEUS and
      orchiectomy. The paired one-tailed Student's t-test was carried out to
      differentiate between Leydig cell tumors and seminomas. RESULTS: 31 lesions
      suspicious for malignancy were hypoechoic on grayscale US while they did not show
      a typical pattern on CDUS. CEUS qualitative analysis, based on contrast
      enhancement pattern, during the arterial and venous phases, did not allow
      discrimination of Leydig cell tumors from seminoma. Quantitative analysis of time
      intensity curves (TICs) demonstrated that only three parameters presented
      statistical significance, i. e. wash-in rate (WiR) p = 0.014, peak enhancement
      (PE) p = 0.001 and time to peak (TTP) p = 0.003. CONCLUSION: The vascular bed of
      a Leydig cell tumor is wider and the blood flow velocity is higher than that of a
      seminoma due to more regular neovascularization. In contrast, a seminoma presents
      large areas of necrosis due to irregular neovascularization. This explains the
      different PE and WiR values. Further studies involving larger patient populations
      are mandatory to confirm these encouraging preliminary results.

PMID- 25607629
TI  - Pulmonary Vasoreactivity to Materno-Fetal Hyperoxygenation Testing in Fetuses
      with Hypoplastic Left Heart.
AB  - PURPOSE: The aim of the study was to describe the response of fetal lung
      vasculature to maternal hyperoxygenation (MH) in the case of prenatally diagnosed
      hypoplastic left heart (HLH) with intact or restrictive (IAS/RAS) and without
      restriction of the atrial septum. Furthermore, the ability of MH to differentiate
      between newborns with HLH who do not require immediate atrial septostomy and
      newborns who will undergo immediate left atrial septoplasty after birth was
      evaluated. MATERIALS AND METHODS: Cross-sectional prospective study of fetuses >=
      26 weeks of gestation with prenatally diagnosed HLH. Lung perfusion (LP) was
      qualitatively assessed by color Doppler interrogation and LP was quantitatively
      measured using the pulsatility index for veins (PIV). Measurements were performed
      both with the mother breathing room air (LPRA) and after receiving 100% oxygen
      for 10 minutes (LPMH). The oxygen test was defined as positive if MH led to an
      increase in lung perfusion and as negative if MH did not lead to an increase.
      RESULTS: A total number of 22 pregnancies with hypoplasia of the left heart
      structures were included. 6/20 cases presented with an intact or restrictive
      atrial septum (IAS/RAS). All of these fetuses presented with a reduced LPRA. MH
      led to an increase in LP in 2/6 cases. The overall 30-day-survival rate was 83.3%
      (5/6). In 14/20 fetuses an open septum was detected. 11 cases had a normal LPRA,
      and the LPRA was reduced in 3/14 fetuses. The overall 30-day-survival rate was
      92.9% (13/14). CONCLUSION: MH might be a useful adjunct in the assessment of
      pulmonary vasculopathy in fetuses with HLH.

PMID- 25607630
TI  - Quantification of Internal Carotid Artery Stenosis with 3D Ultrasound
      Angiography.
AB  - PURPOSE: The aim of this study was to evaluate a new method of three-dimensional
      ultrasound (3D-US) angiography of carotid vessels including 3D-US quantification
      of internal carotid artery (ICA) stenosis (ICAS). MATERIALS AND METHODS: Two
      neurologists performed native ultrasound scans of the brain-supplying carotid
      arteries in 73 probands (including 22 patients with 25 cases of ICAS) using a
      Toshiba Aplio 500 ultrasound machine equipped with the 3 D application of Curefab
      CS. Additionally, 25 probands underwent contrast-enhanced magnetic resonance
      angiography (CE-MRA) of the neck vessels. RESULTS: The mean length of the
      proximal ICA was 32.1 mm +/- 9.8 mm & 31.3 mm +/- 9.0 mm (each n = 97). The
      interrater reliability (intraclass correlation, ICC) was 0.75 +/- 0.23 for the
      common carotid artery (CCA, n = 90) and 0.78 +/- 0.21 (n = 92) for the ICA. The
      intermethod agreement between 3D-US angiography and CE-MRA was 0.67 +/- 0.19 (n =
      45) & 0.66 +/- 0.19 (n = 44) for the CCA and 0.79 +/- 0.17 (n = 47) & 0.75 +/-
      0.19 (n = 46) for the ICA. Quantification of ICAS applying 3D-US in comparison to
      2D color-coded duplexsonography (2D-CDS) showed a moderate to good intermethod
      agreement both by the Bland and Altman analysis and by ICC (0.8 & 0.72; with each
      p < 0.001). The interrater reliability for quantification of ICAS was 0.79; p <
      0.001. CONCLUSION: Native 3D-US angiography of carotid vessels shows good
      interrater and intermethod agreement in comparison to CE-MRA. Together with a
      moderate to good intermethod and interrater agreement in the quantification of
      ICAS, when compared to 2D-CDS, 3D-US angiography is thus a promising
      complementary imaging technique for carotid artery disease.

PMID- 25607631
TI  - Evaluating post-interventional occlusion grades of cerebral aneurysms with
      transcranial contrast-enhanced ultrasound (CEUS) using a matrix probe.
AB  - PURPOSE: The main goal of cerebral endovascular aneurysm therapy is the complete
      occlusion of the aneurysm. Along with the development of new aneurysm treatment
      devices, repeated controls are necessary. We examined whether contrast-enhanced
      ultrasound can help to monitor aneurysms after endovascular treatment. MATERIALS
      AND METHODS: We prospectively examined 12 patients after coiling (7 patients) or
      flow diverter (FD) implantation (5 patients). These patients were examined with
      transcranial contrast-enhanced ultrasound using a matrix probe (1 - 5 MHz).
      Doppler sonography, Power Doppler, contrast harmonic imaging (CHI) and Power
      Doppler sonography (CPD) were included in the examination. Digital subtraction
      angiography with 3 D reconstructions served as the gold standard. Two
      radiologists decided in consensus about the degree of aneurysm occlusion
      separately in CEUS and digital subtraction angiography using a 4-point grading
      scheme. RESULTS: The degree of occlusion of the 12 aneurysms comparing the two
      imaging modalities was identical in 10 cases. In two cases CHI and CPD showed a
      small aneurysm remnant after coiling in the center of the coil pack while in
      digital subtraction angiography the aneurysms seemed completely occluded.
      CONCLUSION: The investigation indicates that contrast-enhanced ultrasound is a
      supportive, noninvasive method for post-interventional controls of intracranial
      aneurysms due to its ability to display not only macro- but also
      microvascularization.

PMID- 25607632
TI  - Ways and Means for the Infusion of Bioactive Constituents in Solid Foods.
AB  - The development and consumption of functional food, or foods that promote health
      not merely basic nutrition, is on rise. In recent years, industrial and consumer
      interests have focused on developing foods supplemented with bioactive
      constituents that provide greater physiological benefits. The direct addition of
      these components to liquid or fabricated solid foods has led to a wide range of
      new products appearing on the market. Osmotic dehydration, an operation in which
      food stuff is soaked in solution of low water activity, has been reported as a
      suitable technology for formulating new products because of the twofold effect
      that it has on food where it partially removes water and impregnates the food
      pieces (solid food matrix) with solutes from the osmotic solution. The article
      focuses on the impregnation of bioactive constituents having added advantage to
      human health such as antioxidants, minerals, vitamins, and probiotics. The
      infusion of enzymes and aroma also has been discussed. Application of ultrasound,
      vacuum, high pressure, and/or atmospheric impregnation techniques appears to be
      the feasible technologies for impregnation of solid food matrix for the
      incorporation of bioactive ingredients. 

PMID- 25607634
TI  - Comment on "Models of care for musculoskeletal health in Australia: now more than
      ever to drive evidence into health policy and practice".

PMID- 25607633
TI  - Development of a cellularly degradable PEG hydrogel to promote articular
      cartilage extracellular matrix deposition.
AB  - Healing articular cartilage remains a significant clinical challenge because of
      its limited self-healing capacity. While delivery of autologous chondrocytes to
      cartilage defects has received growing interest, combining cell-based therapies
      with scaffolds that capture aspects of native tissue and promote cell-mediated
      remodeling could improve outcomes. Currently, scaffold-based therapies with
      encapsulated chondrocytes permit matrix production; however, resorption of the
      scaffold does not match the rate of production by cells leading to generally low
      extracellular matrix outputs. Here, a poly (ethylene glycol) (PEG) norbornene
      hydrogel is functionalized with thiolated transforming growth factor (TGF-beta1)
      and cross-linked by an MMP-degradable peptide. Chondrocytes are co-encapsulated
      with a smaller population of mesenchymal stem cells, with the goal of stimulating
      matrix production and increasing bulk mechanical properties of the scaffold. The
      co-encapsulated cells cleave the MMP-degradable target sequence more readily than
      either cell population alone. Relative to non-degradable gels, cellularly
      degraded materials show significantly increased glycosaminoglycan and collagen
      deposition over just 14 d of culture, while maintaining high levels of viability
      and producing a more widely-distributed matrix. These results indicate the
      potential of an enzymatically degradable, peptide-functionalized PEG hydrogel to
      locally influence and promote cartilage matrix production over a short period.
      Scaffolds that permit cell-mediated remodeling may be useful in designing
      treatment options for cartilage tissue engineering applications.

PMID- 25607635
TI  - Indications and limitations of afamelanotide for treating vitiligo.

PMID- 25607636
TI  - MicroRNA-195 functions as a tumor suppressor by inhibiting CBX4 in hepatocellular
      carcinoma.
AB  - MicroRNA-195 (miR-195) plays important roles in tumor metastasis and
      angiogenesis, yet its function and mechanism of action in hepatocellular
      carcinoma (HCC) remain to be elucidated. In this study, we aimed to confirm
      whether chromobox homolog 4 (CBX4) is a direct target gene of miR-195 and
      determine the functions of miR-195 through the CBX4 pathway. miR-195 expression
      was slightly lower in the HCC tissues compared with that in the adjacent normal
      tissues. In addition, western blotting and qRT-RCR results showed that both CBX4
      mRNA and protein levels were downregulated upon miR-195 overexpression.
      Luciferase reporter assays revealed that CBX4 is a direct target gene of miR-195.
      Furthermore, overexpression of CBX4 significantly restored the proliferative,
      invasive and migratory capacities of the HepG2 cells. Finally, in vivo
      experiments confirmed that high expression of CBX4 in HepG2 cells promoted tumor
      growth. In conclusion, our study demonstrated that miR-195 acts as a tumor
      suppressor by directly targeting CBX4 in HCC. This finding suggests a potential
      novel strategy for therapeutic interventions of this disease.

PMID- 25607637
TI  - Implementation of an innovative nurse-delivered depression intervention for
      mothers of NICU infants.
AB  - Depression affects approximately 19% of all postpartum women, and mounting
      evidence indicates increased risk for mothers of preterm infants, with prevalence
      estimates ranging from 28% to 67%. The current approach to management of maternal
      symptoms related to postpartum depression in the neonatal intensive care unit
      (NICU) ranges from no intervention to depression screening and referral. For
      depressed mothers of NICU infants, obtaining treatment is especially difficult
      and usually becomes a secondary priority; thus, we looked to a nurse-delivered
      counseling model. Listening visits (LV) are an empirically supported nurse
      delivered intervention that focuses on relationship building and exploration of a
      mother's problems through active reflective listening and collaborative problem
      solving. An LV open trial in the NICU has been conducted to evaluate the
      effectiveness of this intervention for mothers of hospitalized infants. Results
      indicate that LV are associated with a reduction in both maternal depressive and
      anxiety symptoms. This case study following the description of the intervention
      demonstrates how the authors used the experiences from the NICU open trial to
      expand the application of LV to this new setting. 

PMID- 25607638
TI  - Endothelin-1 protects human melanocytes from UV-induced DNA damage by activating
      JNK and p38 signalling pathways.
AB  - Endothelin-1 is a paracrine factor with mitogenic, melanogenic and survival
      effects on cultured human melanocytes. We report that endothelin-1 signalling
      reduced the generation and enhanced the repair of ultraviolet radiation (UV)
      induced DNA photoproducts, and inhibited apoptosis of human melanocytes, without
      increasing cAMP levels, melanin content or proliferation. Treatment with
      endothelin-1 activated the MAP kinases JNK and p38, as evidenced by
      phosphorylation of their target, activating transcription factor-2 (ATF-2).
      Endothelin-1 also enhanced the phosphorylation of JNK, p38 and ATF-2 by UV. The
      effects of endothelin-1 were dependent on increasing intracellular calcium
      mobilization by endothelin B receptor signalling. Activation of both JNK and p38
      was required for reducing DNA photoproducts, but only JNK partially contributed
      to the survival effect of endothelin-1. ATF-2 activation depended mainly on JNK,
      yet was not sufficient for the effect of endothelin-1 on UV-induced DNA damage,
      suggesting the requirement for other JNK and p38 targets for this effect. Our
      results underscore the significance of endothelin-1 and endothelin B receptor
      signalling in reducing the genotoxic effects of UV via activating JNK and p38,
      hence restoring genomic stability of melanocytes. 

PMID- 25607639
TI  - Bedtime and sleep timing but not sleep duration are associated with eating habits
      in primary school children.
AB  - OBJECTIVE: In the context of childhood obesity progression, sleep patterns have
      been associated with unhealthy eating habits and energy intake. The association
      between several eating habits and sleep patterns in children has been recently
      studied. The aim of this study was to explore the association between sleep
      patterns, eating habits, and physical fitness in primary school children.
      METHODS: A total of 236 children of 6 to 10 years old were recruited.
      Anthropometric characteristics and body composition were measured, and
      cardiorespiratory (20-m shuttle run test) and musculoskeletal (squat jump and
      cycling peak power) fitness tests were performed. Parents were asked to fill out
      an eating habits questionnaire, and children were classified into 4 categories as
      a function of the number of eating risk factors they presented. Parents completed
      a questionnaire about their child's bedtime and waking hours during weekdays and
      weekends. RESULTS: Weight (p < .01), waist circumference, and fat mass (p < .05)
      were significantly higher in late sleepers (27.6 +/- 6.3 kg; 60.1 +/- 7.6 cm;
      19.52 +/- 7.44) compared with normal sleepers (25.4 +/- 3.7 kg; 58.2 +/- 4.9 cm;
      17.44% +/- 6.23%). None of the physical fitness parameters were associated with
      sleep duration, bedtime, wake-up time, nor were they significantly different
      between late and normal sleepers. Bedtime was significantly earlier in children
      consuming breakfast everyday (08:30 vs. 09:00 PM, p < .01); later in children
      snacking (09:15 vs. 09:30 PM, p < .05) or watching TV at lunch (10:00 vs 09:30
      PM, p < .05). There is an association between the proportion of normal and late
      sleepers and the accumulation of healthy eating habits (p < .001). CONCLUSION:
      Bedtime and sleep timings (normal or late sleepers) are associated with eating
      habits in primary school children. It seems necessary to consider the number of
      unhealthy eating habits adopted by children when studying these associations.

PMID- 25607640
TI  - Signaling factor interactions with polysaccharide aggregates of bacterial
      biofilms.
AB  - Biofilms are surface-attached colonies of bacteria embedded in an extracellular
      polymeric substance (EPS). Inside the eukaryotic hosts, bacterial biofilms
      interact with the host cells through signaling factors (SFs). These signaling
      processes play important roles in the interaction between bacteria and host cells
      and the outcome of infections and symbiosis. However, how host immune factors
      diffuse through biofilms is not well understood. Here, we describe synergistic
      molecular dynamics and experimental approaches for studying the translocation of
      signaling factors through polysaccharide chain aggregates present in the
      extracellular matrix of bacterial biofilms. The effect of polysaccharide chain
      degradation on the energetics of SF-EPS interactions was examined by simulating
      an EPS consisting of various polysaccharide chain lengths. It is shown that the
      SF stabilization energy, defined as the average potential of mean force
      difference between the environments outside and within the matrix, increases
      linearly with decreasing chain length. This effect has been explained based on
      the changes in the polysaccharide configurations around the SF. Specifically,
      shorter chains are packed tightly around the SF, promoting favorable SF-EPS
      interactions, while longer chains are packed loosely resulting in screening of
      interactions with neighboring chains. We further investigated the translocation
      of SFs through the host cell membrane using molecular dynamics simulations.
      Further, simulations predict the existence of energy barriers greater than 1000
      kJ mol(-1) associated with the translocation of the signaling factors necrosis
      factor-alpha (TNF-alpha) and granulocyte macrophage colony stimulating factor (GM
      CSF) across the lipid bilayer. The agreement of computational and experimental
      findings motivates future computational studies using a more detailed description
      of the EPS aimed at understanding the role of the extracellular matrix on biofilm
      drug resistance. 

PMID- 25607641
TI  - WW domains of the yes-kinase-associated-protein (YAP) transcriptional regulator
      behave as independent units with different binding preferences for PPxY motif
      containing ligands.
AB  - YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and
      the object of heightened interest as a potent oncogene and stemness factor. YAP
      has two major isoforms that differ in the number of WW domains they harbor.
      Elucidating the degree of co-operation between these WW domains is important for
      a full understanding of the molecular function of YAP. We present here a detailed
      biophysical study of the structural stability and binding properties of the two
      YAP WW domains aimed at investigating the relationship between both domains in
      terms of structural stability and partner recognition. We have carried out a
      calorimetric study of the structural stability of the two YAP WW domains, both
      isolated and in a tandem configuration, and their interaction with a set of
      functionally relevant ligands derived from PTCH1 and LATS kinases. We find that
      the two YAP WW domains behave as independent units with different binding
      preferences, suggesting that the presence of the second WW domain might
      contribute to modulate target recognition between the two YAP isoforms. Analysis
      of structural models and phage-display studies indicate that electrostatic
      interactions play a critical role in binding specificity. Together, these results
      are relevant to understand of YAP function and open the door to the design of
      highly specific ligands of interest to delineate the functional role of each WW
      domain in YAP signaling. 

PMID- 25607643
TI  - SSZ-87: a borosilicate zeolite with unusually flexible 10-ring pore openings.
AB  - The structure of the as-synthesized borosilicate zeolite SSZ-87 has been solved
      by combining high-resolution X-ray powder diffraction (XPD) and rotation electron
      diffraction (RED) techniques. The unit cell and space group symmetry were found
      from the XPD data, and were essential for the initial analysis of the RED data.
      Although the RED data were only 15% complete, this proved to be enough for
      structure solution with the program Focus. The framework topology is the same as
      that of ITQ-52 (IFW), but for SSZ-87 the locations of the structure directing
      agent (SDA) and the B atoms could also be determined. SSZ-87 has large cages
      interconnected by 8- and 10-rings. However, results of hydroisomerization and Al
      insertion experiments are much more in line with those found for 12-ring
      zeolites. This prompted the structure analyses of SSZ-87 after calcination, and
      Al insertion. During calcination, the material is also partially deboronated, and
      the location of the resulting vacancies is consistent with those of the B atoms
      in the as-synthesized material. After Al insertion, SSZ-87 was found to contain
      almost no B and to be defect free. In its calcined and deboronated form, the pore
      system of SSZ-87 is more flexible than those of other 10-ring zeolites. This can
      be explained by the fact that the large cages in SSZ-87 are connected via single
      rather than double 10-ring windows and that there are vacancies in some of these
      10-rings. 

PMID- 25607642
TI  - The European general practice research network presents the translations of its
      comprehensive definition of multimorbidity in family medicine in ten European
      languages.
AB  - BACKGROUND: Multimorbidity, according to the World Health Organization, exists
      when there are two or more chronic conditions in one patient. This definition
      seems inaccurate for the holistic approach to Family Medicine (FM) and long-term
      care. To avoid this pitfall the European General Practitioners Research Network
      (EGPRN) designed a comprehensive definition of multimorbidity using a systematic
      literature review. OBJECTIVE: To translate that English definition into European
      languages and to validate the semantic, conceptual and cultural homogeneity of
      the translations for further research. METHOD: Forward translation of the EGPRN's
      definition of multimorbidity followed by a Delphi consensus procedure assessment,
      a backward translation and a cultural check with all teams to ensure the
      homogeneity of the translations in their national context. Consensus was defined
      as 70% of the scores being higher than 6. Delphi rounds were repeated in each
      country until a consensus was reached. RESULTS: 229 European medical expert FPs
      participated in the study. Ten consensual translations of the EGPRN comprehensive
      definition of multimorbidity were achieved. CONCLUSION: A comprehensive
      definition of multimorbidity is now available in English and ten European
      languages for further collaborative research in FM and long-term care.

PMID- 25607644
TI  - Competing to coordinate cell fate decisions: the MST2-Raf-1 signaling device.
AB  - How do biochemical signaling pathways generate biological specificity? This
      question is fundamental to modern biology, and its enigma has been accentuated by
      the discovery that most proteins in signaling networks serve multifunctional
      roles. An answer to this question may lie in analyzing network properties rather
      than individual traits of proteins in order to elucidate design principles of
      biochemical networks that enable biological decision-making. We discuss how this
      is achieved in the MST2/Hippo-Raf-1 signaling network with the help of
      mathematical modeling and model-based analysis, which showed that competing
      protein interactions with affinities controlled by dynamic protein modifications
      can function as Boolean computing devices that determine cell fate decisions. In
      addition, we discuss areas of interest for future research and highlight how
      systems approaches would be of benefit. 

PMID- 25607645
TI  - Identification of structural DNA variations in human cell cultures after long
      term passage.
AB  - Random amplified polymorphic DNA (RAPD) analysis was adapted for genomic
      identification of cell cultures and evaluation of DNA stability in cells of
      different origin at different culture passages. DNA stability was observed in
      cultures after no more than 5 passages. Adipose-derived stromal cells
      demonstrated increased DNA instability. RAPD fragments from different cell lines
      after different number of passages were cloned and sequenced. The chromosomal
      localization of these fragments was identified and single-nucleotide variations
      in RAPD fragments isolated from cell lines after 8-12 passages were revealed.
      Some of them had permanent localization, while most variations demonstrated
      random distribution and can be considered as de novo mutations. 

PMID- 25607646
TI  - Polo-like kinase 1 inhibits DNA damage response during mitosis.
AB  - In response to genotoxic stress, cells protect their genome integrity by
      activation of a conserved DNA damage response (DDR) pathway that coordinates DNA
      repair and progression through the cell cycle. Extensive modification of the
      chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases
      enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are
      required for homologous recombination and non-homologous end joining,
      respectively. Whereas mechanisms of DDR are relatively well understood in
      interphase cells, comparatively less is known about organization of DDR during
      mitosis. Although ATM can be activated in mitotic cells, 53BP1 is not recruited
      to the chromatin until cells exit mitosis. Here we report mitotic phosphorylation
      of 53BP1 by Plk1 and Cdk1 that impairs the ability of 53BP1 to bind the
      ubiquitinated H2A and to properly localize to the sites of DNA damage.
      Phosphorylation of 53BP1 at S1618 occurs at kinetochores and in cytosol and is
      restricted to mitotic cells. Interaction between 53BP1 and Plk1 depends on the
      activity of Cdk1. We propose that activity of Cdk1 and Plk1 allows
      spatiotemporally controlled suppression of 53BP1 function during mitosis. 

PMID- 25607647
TI  - The synergistic inhibition of breast cancer proliferation by combined treatment
      with 4EGI-1 and MK2206.
AB  - Cap-dependent translation is a potential cancer-related target (oncotarget) due
      to its critical role in cancer initiation and progression. 4EGI-1, an inhibitor
      of eIF4E/eIF4G interaction, was discovered by screening chemical libraries of
      small molecules. 4EGI-1 inhibits cap-dependent translation initiation by
      impairing the assembly of the eIF4E/eIF4G complex, and therefore is a potential
      anti-cancer agent. Here, we report that 4EGI-1 also inhibits mTORC1 signaling
      independent of its inhibitory role on cap-dependent translation initiation. The
      inhibition of mTORC1 signaling by 4EGI-1 activates Akt due to both abrogation of
      the negative feedback loops from mTORC1 to PI3K and activation of mTORC2. We
      further validated that mTORC2 activity is required for 4EGI-1-mediated Akt
      activation. The activated Akt counteracted the anticancer effects of 4EGI-1. In
      support of this model, inhibition of Akt potentiates the antitumor activity of
      4EGI-1 both in vitro and in a xenograft mouse model in vivo. Our results suggest
      that a combination of 4EGI-1and Akt inhibitor is a rational approach for the
      treatment of cancer. 

PMID- 25607648
TI  - miR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells
      and involved in anti-tumor immune suppression.
AB  - MicroRNAs (miRNAs) play an important role in tumorigenesis, but their role in
      tumor-induced immune suppression is largely unknown. STAT3 signaling, a key
      pathway mediating immune suppression in the tumor microenvironment, is
      responsible for the transcription of several important miRNAs. In this study, we
      observed that miR-146a, a known important regulator of immune responses, was
      downregulated by blocking activated STAT3 in hepatocellular carcinoma (HCC)
      cells. Furthermore, miR-146a inhibition in HCC cells not only altered the STAT3
      activation-associated cytokine profile but also reversed HCC-induced NK cell
      dysfunction in vitro and improved the anti-tumor effect of lymphocytes in vivo.
      Importantly, ChIP and luciferase reporter assays confirmed that STAT3 directly
      bound to the miR-146a promoter and induced miR-146a expression. These findings
      indicated that miR-146a expression was regulated by aberrantly activated STAT3 in
      HCC cells and exerted negative effects on anti-tumor immune response, which
      resulted in the upregulation of cytokines such as TGF-beta, IL-17, VEGF and
      downregulation of type I IFN to create an immunosuppressive microenvironment.
      This further insight into understanding the mechanism responsible for tumor
      induced immune suppression highlights the potential application of miR-146a as a
      novel immunotherapeutic target for HCC. 

PMID- 25607649
TI  - Long ncRNA expression associates with tissue-specific enhancers.
AB  - Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from
      a subset of enhancers and to be required for the distant regulation of gene
      expression. Several approaches to predict enhancers have been developed based on
      various chromatin marks and occupancy of enhancer-binding proteins. Despite the
      rapid advances in the field, no consensus how to define tissue specific enhancers
      yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE
      (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue
      specific enhancers. We use a recently developed algorithm to predict tissue
      specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue
      specific expression of mRNAs. The expression of the long ncRNAs overlapping
      enhancers is significantly higher when the enhancer is predicted as active in a
      specific cell line, suggesting a general interdependency of active enhancers and
      expression of long ncRNAs. This dependency is not identified using previous
      enhancer prediction algorithms that do not account for expression of their
      downstream targets. The predicted enhancers that overlap annotated long ncRNAs
      generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers
      expressing long ncRNAs might be associated with specific epigenetic marks. In
      conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and
      provide evidence for thousands of long ncRNAs that are expressed from active
      tissue-specific enhancers, suggesting a particularly important functional
      relationship between long ncRNAs and enhancer activity in determining tissue
      specific gene expression. 

PMID- 25607650
TI  - The functional repertoire of survivin's tails.
AB  - Survivin is a multitasking protein that can inhibit cell death and that is
      essential for mitosis. Due to these prosurvival activities and the correlation of
      its expression with tumor resistance to conventional cancer treatments, survivin
      has received much attention as a potential oncotherapeutic target. Nevertheless,
      many questions regarding its exact role at the molecular level remain to be
      elucidated. In this study we ask whether the extreme C- and NH2 termini of
      survivin are required for it to carry out its cytoprotective and mitotic duties.
      When assayed for their ability to act as a cytoprotectant, both survivin1-120 and
      survivin11-142 were able to protect cells against TRAIL-mediated apoptosis, but
      when challenged with irradiation cells expressing survivin11-142 had no survival
      advantage. During mitosis, however, removing the NH2 terminal 10 amino acids
      (survivin11-142) had no apparent effect but truncating 22 amino acids from the C
      terminus (survivin1-120) prevented survivin from transferring to the midzone
      microtubules during anaphase. Collectively the data herein presented suggest that
      the C-terminus is required for cell division, and that the NH2 terminus is
      dispensable for apoptosis and mitosis but required for protection from
      irradiation. 

PMID- 25607651
TI  - SIRT6 rescues the age related decline in base excision repair in a PARP1
      dependent manner.
AB  - In principle, a decline in base excision repair (BER) efficiency with age should
      lead to genomic instability and ultimately contribute to the onset of the aging
      phenotype. Although multiple studies have indicated a negative link between aging
      and BER, the change of BER efficiency with age in humans has not been
      systematically analyzed. Here, with foreskin fibroblasts isolated from 19 donors
      between 20 and 64 y of age, we report a significant decline of BER efficiency
      with age using a newly developed GFP reactivation assay. We further observed a
      very strong negative correlation between age and the expression levels of SIRT6,
      a factor which is known to maintain genomic integrity by improving DNA double
      strand break (DSB) repair. Our mechanistic study suggests that, similar to the
      regulatory role that SIRT6 plays in DNA DSB repair, SIRT6 regulates BER in a
      PARP1-depdendent manner. Moreover, overexpression of SIRT6 rescues the decline of
      BER in aged fibroblasts. In summary, our results uncovered the regulatory
      mechanisms of BER by SIRT6, suggesting that SIRT6 reactivation in aging tissues
      may help delay the process of aging through improving BER. 

PMID- 25607653
TI  - Electrostatically induced superconductivity at the surface of WS2.
AB  - We investigate transport through ionic liquid gated field effect transistors
      (FETs) based on exfoliated crystals of semiconducting WS2. Upon electron
      accumulation, at surface densities close to, or just larger than, 10(14) cm(-2),
      transport exhibits metallic behavior with the surface resistivity decreasing
      pronouncedly upon cooling. A detailed characterization as a function of
      temperature and magnetic field clearly shows the occurrence of a gate-induced
      superconducting transition below a critical temperature Tc ~ 4 K, a finding that
      represents the first demonstration of superconductivity in tungsten-based
      semiconducting transition metal dichalcogenides. We investigate the nature of
      superconductivity and find significant inhomogeneity, originating from the local
      detaching of the frozen ionic liquid from the WS2 surface. Despite the
      inhomogeneity, we find that in all cases where a fully developed zero resistance
      state is observed, different properties of the devices exhibit a behavior
      characteristic of a Berezinskii-Kosterlitz-Thouless transition, as it could be
      expected in view of the two-dimensional nature of the electrostatically
      accumulated electron system. 

PMID- 25607652
TI  - KSHV latent protein LANA2 inhibits sumo2 modification of p53.
AB  - Tumor suppressor p53 plays a crucial antiviral role and targeting of p53 by viral
      proteins is a common mechanism involved in virus oncogenesis. The activity of p53
      is tightly regulated at the post-translational levels through a myriad of
      modifications. Among them, modification of p53 by SUMO has been associated with
      the onset of cellular senescence. Kaposi's sarcoma-associated herpesvirus (KSHV)
      expresses several proteins targeting p53, including the latent protein LANA2 that
      regulates polyubiquitylation and phosphorylation of p53. Here we show that LANA2
      also inhibits the modification of p53 by SUMO2. Furthermore, we show that the
      reduction of p53-SUMO2 conjugation by LANA2, as well as the p53-LANA2
      interaction, both require the SUMOylation of the viral protein and its
      interaction with SUMO or SUMOylated proteins in a non-covalent manner. Finally,
      we show that the control of p53-SUMO2 conjugation by LANA2 correlates with its
      ability to inhibit SUMO2- and type I interferon-induced senescence. These results
      highlight the importance of p53 SUMOylation in the control of virus infection and
      suggest that viral oncoproteins could contribute to viral infection and cell
      transformation by abrogating p53 SUMOylation. 

PMID- 25607654
TI  - A new metric of inclusive fitness predicts the human mortality profile.
AB  - Biological species have evolved characteristic patterns of age-specific mortality
      across their life spans. If these mortality profiles are shaped by natural
      selection they should reflect underlying variation in the fitness effect of
      mortality with age. Direct fitness models, however, do not accurately predict the
      mortality profiles of many species. For several species, including humans,
      mortality rates vary considerably before and after reproductive ages, during life
      stages when no variation in direct fitness is possible. Variation in mortality
      rates at these ages may reflect indirect effects of natural selection acting
      through kin. To test this possibility we developed a new two-variable measure of
      inclusive fitness, which we term the extended genomic output or EGO. Using EGO,
      we estimate the inclusive fitness effect of mortality at different ages in a
      small hunter-gatherer population with a typical human mortality profile. EGO in
      this population predicts 90% of the variation in age-specific mortality. This
      result represents the first empirical measurement of inclusive fitness of a trait
      in any species. It shows that the pattern of human survival can largely be
      explained by variation in the inclusive fitness cost of mortality at different
      ages. More generally, our approach can be used to estimate the inclusive fitness
      of any trait or genotype from population data on birth dates and relatedness. 

PMID- 25607656
TI  - Probing the molecular mechanisms in copper amine oxidases by generating
      heterodimers.
AB  - For some homodimeric copper amine oxidases (CuAO), there is suggestive evidence
      of differential activity at the two active sites implying potential cooperativity
      between the two monomers. To examine this phenomenon for the Arthrobacter
      globiformis CuAO (AGAO), we purified a heterodimeric form of the enzyme for
      comparison with the homodimer. The heterodimer comprises an active wild-type
      monomer and an inactive monomer in which an active-site tyrosine is mutated to
      phenylalanine (Y382F). This mutation prevents the formation of the
      trihydroxyphenylalanine quinone (TPQ) cofactor. A pETDuet vector and a dual
      fusion tag strategy was used to purify heterodimers (WT/Y382F) from homodimers.
      Purity was confirmed by western blot and native PAGE analyses. Spectral and
      kinetic studies support the view that whether there are one or two functional
      monomers in the dimer, the properties of each functional monomer are the same,
      thus indicating no communication between the active sites in this bacterial
      enzyme. 

PMID- 25607655
TI  - The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of
      oligodendrocyte development.
AB  - Mutations in GPR56, a member of the adhesion G protein-coupled receptor family,
      cause a human brain malformation called bilateral frontoparietal polymicrogyria
      (BFPP). Magnetic resonance imaging (MRI) of BFPP brains reveals myelination
      defects in addition to brain malformation. However, the cellular role of GPR56 in
      oligodendrocyte development remains unknown. Here, we demonstrate that loss of
      Gpr56 leads to hypomyelination of the central nervous system in mice. GPR56
      levels are abundant throughout early stages of oligodendrocyte development, but
      are downregulated in myelinating oligodendrocytes. Gpr56-knockout mice manifest
      with decreased oligodendrocyte precursor cell (OPC) proliferation and diminished
      levels of active RhoA, leading to fewer mature oligodendrocytes and a reduced
      number of myelinated axons in the corpus callosum and optic nerves. Conditional
      ablation of Gpr56 in OPCs leads to a reduced number of mature oligodendrocytes as
      seen in constitutive knockout of Gpr56. Together, our data define GPR56 as a cell
      autonomous regulator of oligodendrocyte development. 

PMID- 25607657
TI  - Hematopoietic stem/progenitor cells express several functional sex hormone
      receptors-novel evidence for a potential developmental link between hematopoiesis
      and primordial germ cells.
AB  - Evidence has accumulated that hematopoietic stem progenitor cells (HSPCs) share
      several markers with the germline, a connection supported by reports that
      prolactin, androgens, and estrogens stimulate hematopoiesis. To address this
      issue more directly, we tested the expression of receptors for pituitary-derived
      hormones, such as follicle-stimulating hormone (FSH) and luteinizing hormone
      (LH), on purified murine bone marrow (BM) cells enriched for HSPCs and tested the
      functionality of these receptors in ex vivo signal transduction studies and in
      vitro clonogenic assays. We also tested whether administration of pituitary- and
      gonad-derived sex hormones (SexHs) increases incorporation of bromodeoxyuridine
      (BrdU) into HSPCs and expansion of hematopoietic clonogenic progenitors in mice
      and promotes recovery of blood counts in sublethally irradiated animals. We
      report for the first time that HSPCs express functional FSH and LH receptors and
      that both proliferate in vivo and in vitro in response to stimulation by
      pituitary SexHs. Furthermore, based on our observations that at least some of
      CD45(-) very small embryonic-like stem cells (VSELs) may become specified into
      CD45(+) HSPCs, we also evaluated the expression of pituitary and gonadal SexHs
      receptors on these cells and tested whether these quiescent cells may expand in
      vivo in response to SexHs administration. We found that VSELs express SexHs
      receptors and respond in vivo to SexHs stimulation, as evidenced by BrdU
      accumulation. Since at least some VSELs share several markers characteristic of
      migrating primordial germ cells and can be specified into HSPCs, this observation
      sheds new light on the BM stem cell hierarchy. 

PMID- 25607658
TI  - A critical role of the Thy28-MYH9 axis in B cell-specific expression of the Pax5
      gene in chicken B cells.
AB  - Accumulating evidence suggests that Pax5 plays essential roles in B cell lineage
      commitment. However, molecular mechanisms of B cell-specific expression of Pax5
      are not fully understood. Here, we applied insertional chromatin
      immunoprecipitation (iChIP) combined with stable isotope labeling using amino
      acids in cell culture (SILAC) (iChIP-SILAC) to direct identification of proteins
      interacting with the promoter region of the endogenous single-copy chicken Pax5
      gene. By comparing B cells with macrophage-like cells trans-differentiated by
      ectopic expression of C/EBPbeta, iChIP-SILAC detected B cell-specific interaction
      of a nuclear protein, Thy28/Thyn1, with the Pax5 1A promoter. Trans
      differentiation of B cells into macrophage-like cells caused down-regulation of
      Thy28 expression. Loss-of-function of Thy28 induced decrease in Pax5 expression
      and recruitment of myosin-9 (MYH9), one of Thy28-interacting proteins, to the
      Pax5 1A promoter. Loss-of-function of MYH9 also induced decrease in Pax5
      expression. Thus, our analysis revealed that Thy28 is functionally required for B
      cell-specific expression of Pax5 via recruitment of MYH9 to the Pax5 locus in
      chicken B cells. 

PMID- 25607659
TI  - CN: a consensus algorithm for inferring gene regulatory networks using the SORDER
      algorithm and conditional mutual information test.
AB  - Inferring Gene Regulatory Networks (GRNs) from gene expression data is a major
      challenge in systems biology. The Path Consistency (PC) algorithm is one of the
      popular methods in this field. However, as an order dependent algorithm, PC
      algorithm is not robust because it achieves different network topologies if gene
      orders are permuted. In addition, the performance of this algorithm depends on
      the threshold value used for independence tests. Consequently, selecting suitable
      sequential ordering of nodes and an appropriate threshold value for the inputs of
      PC algorithm are challenges to infer a good GRN. In this work, we propose a
      heuristic algorithm, namely SORDER, to find a suitable sequential ordering of
      nodes. Based on the SORDER algorithm and a suitable interval threshold for
      Conditional Mutual Information (CMI) tests, a network inference method, namely
      the Consensus Network (CN), has been developed. In the proposed method, for each
      edge of the complete graph, a weighted value is defined. This value is considered
      as the reliability value of dependency between two nodes. The final inferred
      network, obtained using the CN algorithm, contains edges with a reliability value
      of dependency of more than a defined threshold. The effectiveness of this method
      is benchmarked through several networks from the DREAM challenge and the widely
      used SOS DNA repair network in Escherichia coli. The results indicate that the CN
      algorithm is suitable for learning GRNs and it considerably improves the
      precision of network inference. The source of data sets and codes are available
      at . 

PMID- 25607661
TI  - Air displacement plethysmography versus dual-energy x-ray absorptiometry in
      underweight, normal-weight, and overweight/obese individuals.
AB  - BACKGROUND: Accurately estimating fat percentage is important for assessing
      health and determining treatment course. Methods of estimating body composition
      such as hydrostatic weighing or dual-energy x-ray absorptiometry (DXA), however,
      can be expensive, require extensive operator training, and, in the case of
      hydrostatic weighing, be highly burdensome for patients. Our objective was to
      evaluate air displacement plethysmography via the Bod Pod, a less burdensome
      method of estimating body fat percentage. In particular, we filled a gap in the
      literature by testing the Bod Pod at the lower extreme of the Body Mass Index
      (BMI) distribution. FINDINGS: Three BMI groups were recruited and underwent both
      air displacement plethysmography and dual-energy x-ray absorptiometry. We
      recruited 30 healthy adults at the lower BMI distribution from the Calorie
      Restriction (CR) Society and followers of the CR Way. We also recruited 15 normal
      weight and 19 overweight/obese healthy adults from the general population. Both
      Siri and Brozek equations derived body fat percentage from the Bod Pod, and Bland
      Altman analyses assessed agreement between the Bod Pod and DXA. Compared to DXA,
      the Bod Pod overestimated body fat percentage in thinner participants and
      underestimated body fat percentage in heavier participants, and the magnitude of
      difference was larger for underweight BMI participants, reaching 13% in some. The
      Bod Pod and DXA had smaller discrepancies in normal weight and overweight/obese
      participants. CONCLUSIONS: While less burdensome, clinicians should be aware that
      Bod Pod estimates may deviate from DXA estimates particularly at the lower end of
      the BMI distribution.

PMID- 25607662
TI  - Wastewater treatment performance efficiency of constructed wetlands in African
      countries: a review.
AB  - In Africa, different studies have been conducted at different scales to evaluate
      wastewater treatment efficiency of constructed wetland. This paper aims to review
      the treatment performance efficiency of constructed wetland used in African
      countries. In the reviewed papers, the operational parameters, size and type of
      wetland used and the treatment efficiency are assessed. The results are organized
      and presented in six tables based on the type of wetland and wastewater used in
      the study. The results of the review papers indicated that most of the studies
      were conducted in Tanzania, Egypt and Kenya. In Kenya and Tanzania, different
      full-scale wetlands are widely used in treating wastewater. Among wetland type,
      horizontal subsurface flow wetlands were widely studied followed by surface flow
      and hybrid wetlands. Most of the reported hybrid wetlands were in Kenya. The
      results of the review papers indicated that wetlands are efficient in removing
      organic matter (biochemical oxygen demand and chemical oxygen demand) and
      suspended solids. On the other hand, nutrient removal efficiency appeared to be
      low. 

PMID- 25607660
TI  - A genome-wide investigation of microRNA expression identifies biologically
      meaningful microRNAs that distinguish between high-risk and low-risk intraductal
      papillary mucinous neoplasms of the pancreas.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic
      ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs
      that warrant surgical resection and low-risk IPMNs that can be monitored is a
      significant clinical problem, and we sought to discover a panel of mi(cro)RNAs
      that accurately classify IPMN risk status. METHODOLOGY/PRINCIPAL FINDINGS: In a
      discovery phase, genome-wide miRNA expression profiling was performed on 28
      surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk)
      using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent
      IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA
      expression level and various clinical and pathological factors and examined genes
      and pathways regulated by the identified miRNAs by integrating data from
      bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs
      (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in
      high-risk versus low-risk IPMNs and distinguished between groups (P<10-3, area
      underneath the curve (AUC) = 87%). The same trend was observed in the validation
      phase (AUC = 74%). Low miR-99b expression was associated with main pancreatic
      duct involvement (P = 0.021), and serum albumin levels were positively correlated
      with miR-99a (r = 0.52, P = 0.004) and miR-100 expression (r = 0.49, P = 0.008).
      Literature, validated miRNA:target gene interactions, and pathway enrichment
      analysis supported the candidate miRNAs as tumor suppressors and regulators of
      PDAC development. Microarray analysis revealed that oncogenic targets of miR-130a
      (ATG2B, MEOX2), miR-342-3p (DNMT1), and miR-126 (IRS-1) were up-regulated in high
      versus low-risk IPMNs (P<0.10). CONCLUSIONS: This pilot study highlights miRNAs
      that may aid in preoperative risk stratification of IPMNs and provides novel
      insights into miRNA-mediated progression to pancreatic malignancy. The miRNAs
      identified here and in other recent investigations warrant evaluation in
      biofluids in a well-powered prospective cohort of individuals newly-diagnosed
      with IPMNs and other pancreatic cysts and those at increased genetic risk for
      these lesions.

PMID- 25607663
TI  - Dewatering as a non-toxic control of nuisance midge larvae in algal wastewater
      treatment floways.
AB  - Attached-algae floways have tremendous potential for use in wastewater treatment
      because natural algal communities show high nutrient removal efficiencies, have
      low operating costs, and are easy to maintain. Algal wastewater floways may also
      serve as a sustainable option for producing renewable energy because algae grow
      rapidly, are easily harvested, and can serve as a source of biomass for biofuel.
      However, pests such as chironomids (Diptera) colonize open channel periphyton
      floways and their larvae damage the biofilms. While pesticides can control midge
      larvae, little information is known about alternative, non-toxic controls. This
      study examined the effectiveness of periodic, short-term dewatering (4 hours
      every 9 days) on midge abundance and periphyton growth in 16 recirculating,
      outdoor floways (3 m long, 0.1 m wide). We compared midge abundance and algal
      accumulation (chlorophyll a, b, c, and pheophytin) among control (n=8) and
      dewatered (n=8) floways filled with secondarily treated wastewater (27 days, 10
      hours of daylight). Dewatered flumes had 42% fewer midges and 28-49% lower algal
      productivity (as measured by chlorophyll a, b, c, and pheophytin pigments).
      Chlorophyll a production rates averaged (+/-1 SD) 0.5+/-0.2 MUg/cm2/day in
      control floways compared to 0.3+/-0.1 MUg/cm2/day dewatered floways. Short-term
      dewatering effectively reduced midges but also damaged periphyton. To maximize
      the recovery of periphyton biomass, operators should harvest periphyton from
      floways during dewatering events before periphyton is damaged by desiccation or
      direct exposure to sunlight.

PMID- 25607664
TI  - Modeling bioaugmentation with nitrifiers in membrane bioreactors.
AB  - Bioaugmentation with nitrifiers was studied using two pilot-scale membrane
      bioreactors, with the purpose of assessing the suitability of state-of-the-art
      activated sludge models (ASMs) in predicting the efficiency of bioaugmentation as
      a function of operating conditions. It was demonstrated that the temperature
      difference between seeding and seeded reactors (DeltaT) affects bioaugmentation
      efficiency. Experimental data were accurately predicted when DeltaT was within a
      range of up to 10  degrees C at the higher range, and when the temperature was
      significantly lower in the seeded reactor compared to the seeding one, standard
      ASMs overestimated the efficiency of bioaugmentation. A modified ASM, capable of
      accurately representing the behavior of seeded nitrifying biomass in the presence
      of high DeltaT, would require the inclusion of the effect of temperature time
      gradients on nitrifiers. A simple linear correlation between DeltaT and the
      Arrhenius coefficient was proposed as a preliminary step. 

PMID- 25607665
TI  - Adaptive neuro-fuzzy inference system for real-time monitoring of integrated
      constructed wetlands.
AB  - Monitoring large-scale treatment wetlands is costly and time-consuming, but
      required by regulators. Some analytical results are available only after 5 days
      or even longer. Thus, adaptive neuro-fuzzy inference system (ANFIS) models were
      developed to predict the effluent concentrations of 5-day biochemical oxygen
      demand (BOD5) and NH4-N from a full-scale integrated constructed wetland (ICW)
      treating domestic wastewater. The ANFIS models were developed and validated with
      a 4-year data set from the ICW system. Cost-effective, quicker and easier to
      measure variables were selected as the possible predictors based on their
      goodness of correlation with the outputs. A self-organizing neural network was
      applied to extract the most relevant input variables from all the possible input
      variables. Fuzzy subtractive clustering was used to identify the architecture of
      the ANFIS models and to optimize fuzzy rules, overall, improving the network
      performance. According to the findings, ANFIS could predict the effluent quality
      variation quite strongly. Effluent BOD5 and NH4-N concentrations were predicted
      relatively accurately by other effluent water quality parameters, which can be
      measured within a few hours. The simulated effluent BOD5 and NH4-N concentrations
      well fitted the measured concentrations, which was also supported by relatively
      low mean squared error. Thus, ANFIS can be useful for real-time monitoring and
      control of ICW systems. 

PMID- 25607666
TI  - Commercial microwave links instead of rain gauges: fiction or reality?
AB  - Commercial microwave links (MWLs) were suggested about a decade ago as a new
      source for quantitative precipitation estimates (QPEs). Meanwhile, the theory is
      well understood and rainfall monitoring with MWLs is on its way to being a mature
      technology, with several well-documented case studies, which investigate QPEs
      from multiple MWLs on the mesoscale. However, the potential of MWLs to observe
      microscale rainfall variability, which is important for urban hydrology, has not
      been investigated yet. In this paper, we assess the potential of MWLs to capture
      the spatio-temporal rainfall dynamics over small catchments of a few square
      kilometres. Specifically, we investigate the influence of different MWL
      topologies on areal rainfall estimation, which is important for experimental
      design or to a priori check the feasibility of using MWLs. In a dedicated case
      study in Prague, Czech Republic, we collected a unique dataset of 14 MWL signals
      with a temporal resolution of a few seconds and compared the QPEs from the MWLs
      to reference rainfall from multiple rain gauges. Our results show that, although
      QPEs from most MWLs are probably positively biased, they capture spatio-temporal
      rainfall variability on the microscale very well. Thus, they have great potential
      to improve runoff predictions. This is especially beneficial for heavy rainfall,
      which is usually decisive for urban drainage design. 

PMID- 25607667
TI  - Removal and bioaccumulation of heavy metals from aqueous solutions using
      freshwater algae.
AB  - Four freshwater algae, including Cladophora glomerata, Oedogonium westii,
      Vaucheria debaryana and Zygnema insigne, were tested for their bioaccumulation
      capacity for cadmium (Cd), chromium (Cr) and lead (Pb) in a controlled
      environment with an average temperature of 18  degrees C, and light/dark duration
      of 12:12 h. Experiments were performed in aqueous solutions containing selected
      heavy metals (HM) (ranging from 0.05 to 1.5 mg L(-1)) with 0.5 g of living algae
      at 18  degrees C and pH 6.8. The results indicated that C. glomerata was observed
      to be the most competent species for the removal of Cr, Cd and Pb from aqueous
      solutions. HM removal trends were in the order of Cd>Cr>Pb while the removal
      efficiency of selected algae species was in the order of C. glomerata, O. westii,
      V. debaryana and Z. insigne. The bioaccumulation capacity of C. glomerata, V.
      debaryana and Z. insigne was observed for different HM. Removal of HM was higher
      with low levels of HM in aqueous solutions. The results indicated that C.
      glomerata, O. westii, V. debaryana and Z. insigne had significant (P<=0.01)
      diverse bioaccumulation capacity for Cr, Cd and Pb.

PMID- 25607668
TI  - Influence of local calibration on the quality of online wet weather discharge
      monitoring: feedback from five international case studies.
AB  - This paper reports about experiences gathered from five online monitoring
      campaigns in the sewer systems of Berlin (Germany), Graz (Austria), Lyon (France)
      and Bogota (Colombia) using ultraviolet-visible (UV-VIS) spectrometers and
      turbidimeters. Online probes are useful for the measurement of highly dynamic
      processes, e.g. combined sewer overflows (CSO), storm events, and river impacts.
      The influence of local calibration on the quality of online chemical oxygen
      demand (COD) measurements of wet weather discharges has been assessed. Results
      underline the need to establish local calibration functions for both UV-VIS
      spectrometers and turbidimeters. It is suggested that practitioners calibrate
      locally their probes using at least 15-20 samples. However, these samples should
      be collected over several events and cover most of the natural variability of the
      measured concentration. For this reason, the use of automatic peristaltic
      samplers in parallel to online monitoring is recommended with short
      representative sampling campaigns during wet weather discharges. Using reliable
      calibration functions, COD loads of CSO and storm events can be estimated with a
      relative uncertainty of approximately 20%. If no local calibration is
      established, concentrations and loads are estimated with a high error rate,
      questioning the reliability and meaning of the online measurement. Similar
      results have been obtained for total suspended solids measurements. 

PMID- 25607669
TI  - Two-phase anaerobic co-digestion of food waste and sewage sludge.
AB  - The feasibility and performance of food waste and sewage sludge co-digestion were
      investigated to gain insight into their resource utilization. In this study, two
      phase anaerobic digestion (TPAD) was operated under a total solids mixing ratio
      of 1:1 and different sludge retention times (SRTs). Results show that an
      acidogenic reactor with a 5-day SRT obtained the highest acidification
      efficiency, and its acetic acid content was dominant. The organic removal rate of
      a methanogenic reactor (MR) with a 20-day SRT and its corresponding TPAD system
      with a 25-day SRT were both the highest among the MRs and TPAD systems. Volatile
      solids and total chemical oxygen demand average removal efficiencies of the TPAD
      system with a 25-day SRT reached 64.7 and 60.8%, respectively. The MR with a 30
      day SRT obtained the minimum ratio of volatile fatty acid to alkalinity (0.12).
      The methane content generated from the different MRs fluctuated at around 70%.
      All of the above results can provide reference for future research. 

PMID- 25607670
TI  - Scale-dependence effects of landscape on seasonal water quality in Xitiaoxi
      catchment of Taihu Basin, China.
AB  - Further understanding the mechanisms of landscape-water interactions is of great
      importance to water quality management in the Xitiaoxi catchment. Pearson's
      correlation analysis, stepwise multiple regression and redundancy analysis were
      adopted in this study to investigate the relation between water quality and
      landscape at the sub-catchment and 200 m riparian zone scales during dry and wet
      seasons. Landscape was characterized by natural environmental factors, land use
      patterns and four selected landscape configuration metrics. The obtained results
      indicated that land use categories of urban and forest were dominant landscape
      attributes, which influenced water quality. Natural environment and landscape
      configuration were overwhelmed due to land management activities and hydrologic
      conditions. In general, the landscape of the 200 m riparian zone appeared to have
      slightly greater influence on water than did the sub-catchment, and water quality
      was slightly better explained by all landscape attributes in the wet season than
      in the dry season. The results suggested that management efforts aimed at
      maintaining and restoring river water quality should currently focus on the
      protection of riparian zones and the development of an updated long-term
      continuous data set and higher resolution digital maps to discuss the minimum
      width of the riparian zone necessary to protect water quality. 

PMID- 25607671
TI  - Alkaline treatment of high-solids sludge and its application to anaerobic
      digestion.
AB  - High-solids anaerobic digestion is a promising new process for sludge reduction
      and bioenergy recovery, requiring smaller digestion tanks and less energy for
      heating, but a longer digestion time, than traditional low-solids anaerobic
      digestion. To accelerate this process, alkaline sludge disintegration was tested
      as a pretreatment method for anaerobic digestion of high-solids sludge. The
      results showed that alkaline treatment effectively disintegrated both low-solids
      sludge and high-solids sludge, and treatment duration of 30 min was the most
      efficient. The relation between sludge disintegration degree and NaOH dose can be
      described by a transmutative power function model. At NaOH dose lower than 0.2
      mol/L, sludge disintegration degree remained virtually unchanged when sludge
      total solids (TS) content increased from 2.0 to 11.0%, and decreased only
      slightly when sludge TS increased to 14.2%. Although high-solids sludge required
      a slightly higher molarity of NaOH to reach the same disintegration level of low
      solids sludge, the required mass of NaOH actually decreased due to sludge
      thickening. From the view of NaOH consumption, sludge TS of 8-12% and a NaOH dose
      of 0.05 mol/L were optimum conditions for alkaline pretreatment, which resulted
      in a slight increase in accumulative biogas yield, but a decrease by 24-29% in
      digestion time during the subsequent anaerobic digestion. 

PMID- 25607673
TI  - The study of capacitive deionization behavior of a carbon nanotube electrode from
      the perspective of charge efficiency.
AB  - In this work, the capacitive deionization (CDI) performance of a single-walled
      carbon nanotube (CNT) electrode has been studied from the point view of charge
      efficiency theory. It is revealed here that the charge efficiency of a CNT
      electrode is strongly dependent upon the cell voltage and solution concentration.
      Either the high cell voltage or the low ionic strength results in a high charge
      efficiency, implying that CDI is expected to be a promising technique for an
      aqueous solution with low ionic strength. Additionally, it is found that the high
      decay constant and high electrical double-layer capacity are beneficial to
      enhance electrosorption performance. 

PMID- 25607672
TI  - Characteristics of hydrocarbon hydroxylase genes in a thermophilic aerobic
      biological system treating oily produced wastewater.
AB  - Alkane and aromatic hydroxylase genes in a full-scale aerobic system treating
      oily produced wastewater under thermophilic condition (45-50  degrees C) in the
      Jidong oilfield, China, were investigated using clone library and quantitative
      polymerase chain reaction methods. Rather than the normally encountered integral
      membrane non-haem iron monooxygenase (alkB) genes, only CYP153-type P450
      hydroxylase genes were detected for the alkane activation, indicating that the
      terminal oxidation of alkanes might be mainly mediated by the CYP153-type alkane
      hydroxylases in the thermophilic aerobic process. Most of the obtained CYP153
      gene clones showed distant homology with the reference sequences, which might
      represent novel alkane hydroxylases. For the aromatic activation, the polycyclic
      aromatic hydrocarbon-ring hydroxylating dioxygenase (PAH-RHD) gene was derived
      from Gram-negative PAH-degraders belonging to the Burkholderiales order, with a
      0.72% relative abundance of PAH-RHD gene to 16S rRNA gene. This was consistent
      with the result of 16S rRNA gene analysis, indicating that Burkholderiales
      bacteria might play a key role in the full-scale process of thermophilic
      hydrocarbon degradation. 

PMID- 25607674
TI  - Predicting wastewater temperatures in sewer pipes using abductive network models.
AB  - A predictive modelling technique was employed to estimate wastewater temperatures
      in sewer pipes. The simplicity of abductive predictive models attracts large
      numbers of users due to their minimal computation time and limited number of
      measurable input parameters. Data measured from five sewer pipes over a period of
      12 months provide 33,900 training entries and 39,000 evaluation entries to
      support the models' development. Two simple predictive models for urban upstream
      combined sewers and large downstream collector sewers were developed. They
      delivered good correlation between measured and predicted wastewater temperatures
      proven by their R(2) values of up to 0.98 and root mean square error (RMSE) of
      the temperature change along the sewer pipe ranging from 0.15  degrees C to 0.33 
      degrees C. Analysis of a number of potential input parameters indicated that
      upstream wastewater temperature and downstream in-sewer air temperature were the
      only input parameters that are needed in the developed models to deliver this
      level of accuracy. 

PMID- 25607675
TI  - Effect of sulfate and lactate loading rates on the respiration process and
      microbial population changes measured by ecological indices.
AB  - In a sulfate reducing process, increasing loading rates and sulfide accumulation
      may induce population changes resulting in decreasing effectiveness of the
      process. Thus, the relationship between microbial metabolism changes and
      population dynamics was studied. An upflow anaerobic sludge blanket reactor was
      operated at different sulfate loading rates (SLR), from 290 to 981 mg SO4-S/L d
      at a constant carbon/sulfur ratio of 0.75. When the SLR was increased, the total
      organic carbon and sulfate consumption efficiencies decreased to nearly 30% and
      25%, respectively. The acetate and propionate yields increased with increasing
      SLR and 385+/-7 mg sulfide-S/L d was reached. The ecological indices, determined
      by random amplified polymorphic DNA and denaturing gradient gel electrophoresis
      techniques, diversity and evenness were found to be constant, and similarity
      coefficient values remained higher than 76%. The results suggest that the
      microbial population changes were negligible compared with metabolic changes when
      SLR was increased. The sulfide accumulation did not modify the microbial
      diversity. The sequencing of 16S rRNA genes showed strains related to sulfate
      reducing, fermentation, and methanogenesis processes. The results indicated that
      the decreasing of effectiveness, under the experimental conditions tested, was
      dependent more on operational parameters than microbial changes.

PMID- 25607676
TI  - Biohydrogen production from industrial wastewaters.
AB  - The feasibility of producing hydrogen from various industrial wastes, such as
      vinasses (sugar and tequila industries), and raw and physicochemical-treated
      wastewater from the plastic industry and toilet aircraft wastewater, was
      evaluated. The results showed that the tequila vinasses presented the maximum
      hydrogen generation potential, followed by the raw plastic industry wastewater,
      aircraft wastewater, and physicochemical-treated wastewater from the plastic
      industry and sugar vinasses, respectively. The hydrogen production from the
      aircraft wastewater was increased by the adaptation of the microorganisms in the
      anaerobic sequencing batch reactor. 

PMID- 25607677
TI  - Study of the sludge reduction in an oxic-settling-anaerobic activated sludge
      process based on UNITANK.
AB  - An oxic-settling-anaerobic process (OSA) can effectively reduce sludge
      production, but most of the research studies on the OSA process have been either
      under laboratory test conditions or based on synthetic wastewater, which cannot
      fully reflect the performance and sludge reduction efficiency in existing OSA
      process. Thus, aiming at examining the sludge reduction efficiency and the
      stability of the OSA process, UNITANK and UNITANK-OSA processes were performed in
      a 120 m(3)/d pilot-scale system using actual sewage. The results indicate that
      UNITANK-OSA achieved a 48% reduction of the sludge compared to the reduction due
      to UNITANK, not considering the accumulation of the effluent-suspended solids.
      The effluent quality was not found to change significantly, except that the total
      phosphorus concentration increased slightly. The extracellular polymeric
      substances metal floc theory may, to some extent, explain this reduction in this
      study. The OSA process could be used to reform the classic wastewater treatment
      process to get lower sludge mass. 

PMID- 25607678
TI  - Characterization of organic fouling in reverse osmosis membranes by headspace
      solid phase microextraction and gas chromatography-mass spectrometry.
AB  - Adsorption of organic substances on reverse osmosis (RO) membrane surfaces may
      form an organic film on the membrane, known as organic fouling, and cause flow
      rate loss. This problem is mostly unavoidable as no pretreatment method exists
      for perfect removal of possible foulants, including organic compounds resulting
      from undesirable bioactivity. Understanding the characteristics of fouling layers
      is an essential step towards overall improvement of RO membrane operations. In
      this study, the organic fouling in RO membranes treating the effluent of a
      secondary treatment from an urban wastewater treatment plant was characterized.
      Headspace solid phase microextraction (HS-SPME) coupled with gas chromatography
      mass spectrometry has been used for the first time, to provide valuable
      information of organic fouling. Different polarity SPME fibers were tested for
      this purpose. In addition, the characterization of the organic fouling obtained
      by HS-SPME was compared with the results obtained by extraction using several
      organic solvents. The results indicated that more compound families can be
      identified by HS-SPME than by organic solvent extraction. Moreover, complementary
      organic analyses were done for better understanding of the organic fouling in RO
      membranes, such as total organic carbon and loss on ignition. 

PMID- 25607679
TI  - Comparative study on electrochemical 4-chlorophenol degradation in different
      diaphragm systems with combined reduction and oxidation properties.
AB  - Two diaphragm electrolysis systems, two-electrode (anode-cathode) and three
      electrode (cathode-anode-cathode), were compared for the electrochemical
      degradation of 4-chlorophenol. The performance of these systems was improved by
      feeding with hydrogen gas and then with air, in aid of the combined processes of
      reduction and oxidation. The 4-chlorophenol degradation, dechlorination, and
      total organic carbon removal were monitored to characterize the difference
      between the two systems. The results indicated that the three-electrode system
      exhibited higher degradation percentages for 4-chlorophenol compared with that of
      the two-electrode system. The dechlorination property of the three-electrode
      system was stronger than that of the two-electrode system. In addition, the total
      organic carbon removal percentage of the anodic compartment in the three
      electrode system was higher than that of the two-electrode system. The three
      electrode system showed excellent treatment properties for 4-chlorophenol. 

PMID- 25607680
TI  - Basis for the development of sustainable optimisation indicators for activated
      sludge wastewater treatment plants in the Republic of Ireland.
AB  - This paper describes the basis of a stakeholder-based sustainable optimisation
      indicator (SOI) system to be developed for small-to-medium sized activated sludge
      (AS) wastewater treatment plants (WwTPs) in the Republic of Ireland (ROI). Key
      technical publications relating to best practice plant operation, performance
      audits and optimisation, and indicator and benchmarking systems for wastewater
      services are identified. Optimisation studies were developed at a number of Irish
      AS WwTPs and key findings are presented. A national AS WwTP manager/operator
      survey was carried out to verify the applied operational findings and identify
      the key operator stakeholder requirements for this proposed SOI system. It was
      found that most plants require more consistent operational data-based decision
      making, monitoring and communication structures to facilitate optimised,
      sustainable and continuous performance improvement. The applied optimisation and
      stakeholder consultation phases form the basis of the proposed stakeholder-based
      SOI system. This system will allow for continuous monitoring and rating of plant
      performance, facilitate optimised operation and encourage the prioritisation of
      performance improvement through tracking key operational metrics. Plant
      optimisation has become a major focus due to the transfer of all ROI water
      services to a national water utility from individual local authorities and the
      implementation of the EU Water Framework Directive. 

PMID- 25607681
TI  - Removal and recovery of lead (Pb2+) from industrial effluent using indigenous and
      tailor-made Aureobasidium sp. RBSS-303.
AB  - The objective of this study was to assess the removal and recovery of Pb-II from
      industrial wastewater using a locally isolated strain of Aureobasidium sp. RBSS
      303. The initial Pb2+ concentration of 600 mg/L resulted in maximum uptake
      capacity (Qmax 235.1+/-0.3 mg/g). The biosorbent revival was attained by
      contacting with HCl (0.01 M), with 75.3% recovery of Pb2+. The Freundlich
      isotherm best explains the Pb2+ sorption performances. Maximum adsorption
      distribution coefficient of 1,309.6 mg metal/mL was observed at initial Pb2+
      concentration value of 100 mg/L. Evaluation of nine kinetic models showed the
      removal rate of Pb2+ was reliant on diffusion control pseudo-second-order and
      saturation-mixed-order kinetic models with a high correlation coefficient value
      (R=0.99). Fourier transform infrared spectroscopy analysis showed the major
      contribution of -NH2 and -CN ligands of Aureobasidium sp. RBSS-303 in the
      sorption phenomenon of Pb2+. The biosorption assays carried out with effluent of
      the paint industry showed 76.8% efficiency for Pb2+ removal by the candidate
      biosorbent, regardless of the complex composition of the industrial effluent.

PMID- 25607682
TI  - Can we model the implementation of water sensitive urban design in evolving
      cities?
AB  - This study showcases the dynamic simulation capabilities of the Urban Biophysical
      Environments And Technologies Simulator (UrbanBEATS) on a Melbourne catchment.
      UrbanBEATS simulates the planning, design and implementation of water sensitive
      urban design (WSUD) infrastructure in urban environments. It considers explicitly
      the interaction between urban and water infrastructure planning through time. The
      model generates a large number of realizations of different WSUD interventions
      and their evolution through time based on a user-defined scenario. UrbanBEATS'
      dynamics was tested for the first time on a historical case study of Scotchman's
      Creek catchment and was trained using historical data (e.g. planning documents,
      narratives, urban development and societal information) to adequately reproduce
      patterns of uptake of specific WSUD technologies. The trained model was also used
      to explore the implications of more stringent future water management objectives.
      Results highlighted the challenges of meeting this legislation and the
      opportunities that can be created through the mix of multiple spatial scales. 

PMID- 25607683
TI  - Erratum: Water Science and Technology 56(3), 2007, 233-240: Comparison of
      measured and simulated distribution of microbial biomass in subsurface vertical
      flow constructed wetlands.

PMID- 25607685
TI  - Dental and skeletal changes in mild to moderate Class II malocclusions treated by
      either a Twin-block or Xbow appliance followed by full fixed orthodontic
      treatment.
AB  - OBJECTIVE: To compare the short-term skeletal and dental effects of two-phase
      orthodontic treatment including either a Twin-block or an XBow appliance.
      MATERIALS AND METHODS: This was a retrospective clinical trial of 50 consecutive
      Class II cases treated in a private practice with either a Twin-block (25) or
      XBow (25) appliance followed by full fixed orthodontic treatment. To factor out
      growth, an untreated Class II control group (25) was considered. RESULTS: A
      MANOVA of treatment/observation changes followed by univariate pairwise
      comparisons showed that the maxilla moved forward less in the treatment groups
      than in the control group. As for mandibular changes, the corpus length increase
      was larger in the Twin-block group by 3.9 mm. Dentally, mesial movement of
      mandibular molars was greater in both treatment groups. Although no distalization
      of maxillary molars was found in either treatment group, restriction of mesial
      movement of these teeth was seen in both treatment groups. Both treatment groups
      demonstrated increased mandibular incisor proclination with larger increases for
      the XBow group by 3.3 degrees . The Wits value was decreased by 1.6 mm more in
      the Twin-block group. No sex-related differences were observed. CONCLUSIONS:
      Class II correction using an XBow or Twin-block followed by fixed appliances
      occurs through a relatively similar combination of dental and skeletal effects.
      An increase in mandibular incisor inclination for the XBow group and an increased
      corpus length for the Twin-block group were notable exceptions. No overall
      treatment length differences were seen.

PMID- 25607686
TI  - An iron-based green approach to 1-h production of single-layer graphene oxide.
AB  - As a reliable and scalable precursor of graphene, graphene oxide (GO) is of great
      importance. However, the environmentally hazardous heavy metals and poisonous
      gases, explosion risk and long reaction times involved in the current synthesis
      methods of GO increase the production costs and hinder its real applications.
      Here we report an iron-based green strategy for the production of single-layer GO
      in 1 h. Using the strong oxidant K2FeO4, our approach not only avoids the
      introduction of polluting heavy metals and toxic gases in preparation and
      products but also enables the recycling of sulphuric acid, eliminating pollution.
      Our dried GO powder is highly soluble in water, in which it forms liquid crystals
      capable of being processed into macroscopic graphene fibres, films and aerogels.
      This green, safe, highly efficient and ultralow-cost approach paves the way to
      large-scale commercial applications of graphene.

PMID- 25607684
TI  - Elongator, a conserved complex required for wobble uridine modifications in
      eukaryotes.
AB  - Elongator is a 6 subunit protein complex highly conserved in eukaryotes. The role
      of this complex has been controversial as the pleiotropic phenotypes of Elongator
      mutants have implicated the complex in several cellular processes. However, in
      yeast there is convincing evidence that the primary and probably only role of
      this complex is in formation of the 5-methoxycarbonylmethyl (mcm(5)) and 5
      carbamoylmethyl (ncm(5)) side chains on uridines at wobble position in tRNA. In
      this review we summarize the cellular processes that have been linked to the
      Elongator complex and discuss its role in tRNA modification and regulation of
      translation. We also describe additional gene products essential for formation of
      ncm(5) and mcm(5) side chains at U34 and their influence on Elongator activity. 

PMID- 25607687
TI  - Chemistry specificity of DNA-polycation complex salt response: a simulation study
      of DNA, polylysine and polyethyleneimine.
AB  - In this work, the chemistry specific stability determining factors of DNA
      polycation complexes are examined by performing all-atom molecular dynamics
      simulations. To this end, we conduct a systematic variation of polycation line
      charge through polyethyleneimine (PEI) protonation and polycation chemistry via
      comparison with poly-l-lysine (PLL). Our simulations show that increasing line
      charge of the polycation alone does not lead to more salt tolerant complexes.
      Instead, the effective charge compensation by the polycation correlates with the
      increased stability of the complex against additional salt. The salt stability of
      PEI-DNA complexes also links to the proton sponge property of weak polycations,
      commonly assumed to be behind the effectivity of PEI as a gene delivery vector.
      Examination of the complexes reveals the mechanism behind this behaviour; more
      Cl(-) ions are attracted by the protonated complexes but, in contrast to the
      common depiction of the proton sponge behaviour, the ion influx does not cause
      swelling of the complex structure itself. However, PEI protonation leads to
      release of PEI while DNA remains tightly bound to the complex. Jointly, these
      findings shed light on the stability determining factors of DNA-polycation
      complexes, raise charge distribution as an important stability determining
      contributor, and indicate that the effectivity of PEI in gene delivery is likely
      to result from the freed PEI facilitating gene transfection. 

PMID- 25607688
TI  - The traditional Chinese medicinal formula BDL301 suppresses tumor growth by
      inhibiting STAT3 pathway and inducing apoptosis in colorectal cancer cells.
AB  - The traditional Chinese medicinal formula BDL301 has been used to inhibit
      inflammation for hundreds of years. The development of colorectal cancer and
      chronic inflammation are closely related. In this study, we investigated whether
      BDL301 could inhibit tumor growth. We found that angiogenesis and tumor growth
      were both inhibited in vivo. In addition, apoptosis was induced and the signal
      transducer and activator of transcription-3 (STAT3) pathway were suppressed in
      the colorectal cancer cells in vitro and in vivo by BDL301. This study
      demonstrates that BDL301 exerted significant anticancer activity by inhibiting
      the STAT3 pathways and inducing apoptosis in colorectal cancer cells. 

PMID- 25607689
TI  - Correction: comparative genomic analysis of primary and synchronous metastatic
      colorectal cancers.

PMID- 25607690
TI  - Uncovering the spatial structure of mobility networks.
AB  - The extraction of a clear and simple footprint of the structure of large,
      weighted and directed networks is a general problem that has relevance for many
      applications. An important example is seen in origin-destination matrices, which
      contain the complete information on commuting flows, but are difficult to analyze
      and compare. We propose here a versatile method, which extracts a coarse-grained
      signature of mobility networks, under the form of a 2 * 2 matrix that separates
      the flows into four categories. We apply this method to origin-destination
      matrices extracted from mobile phone data recorded in 31 Spanish cities. We show
      that these cities essentially differ by their proportion of two types of flows:
      integrated (between residential and employment hotspots) and random flows, whose
      importance increases with city size. Finally, the method allows the determination
      of categories of networks, and in the mobility case, the classification of cities
      according to their commuting structure. 

PMID- 25607691
TI  - Drought planning and management: using high spatial resolution as part of the
      solution.
AB  - Water scarcity is intensified by drought, a phenomenon that impacts many sectors
      of society and affects virtually all climate zones. The Palmer drought indices
      are widely used by scientists and policy makers to understand drought and model
      its components. Despite the spatial heterogeneity and variability in variables
      required by the Palmer model, regional index values are most commonly used for
      real-time drought assessment. Local stakeholders charged with developing flexible
      and tailored water management policies have articulated the need for drought
      indices calculated at finer spatial resolutions than a regional scale. We use the
      Pacific Northwest United States (U.S.) as a study area to demonstrate the
      differences between drought indices calculated for U.S. climate divisions with
      those calculated at a 0.5 degrees  by 0.5 degrees  latitude/longitude resolution.
      Our results indicate that regional values of the two cumulative Palmer drought
      indices do not represent finer-resolution values well. For half of the study
      area, the pictures of drought (as determined by regional and finer-resolution
      values) are drastically different more than 30% of the time. Thus, quite often
      water managers do not have a clear understanding of the relative severity of
      drought in their area, which can have serious implications for drought mitigation
      and adaptation. 

PMID- 25607692
TI  - Ultrasound technologies for dermatologic applications.

PMID- 25607693
TI  - Update on male pattern hair loss.

PMID- 25607694
TI  - VISIA system: a possible tool in the cosmetic practice.
AB  - BACKGROUND: Dyspigmentation is a common complaint in the dermatology office.
      OBJECTIVE: We also sought to evaluate whether the VISIA Complexion Analysis
      System (Canfield Imaging Systems, Fairfield, NJ) could be a tool to help patients
      better understand their skin complaints. METHODS: Twenty-one consecutive women
      were recruited for VISIA analysis. Each subject underwent VISIA analysis and
      completed a follow up survey. RESULTS: 86% of respondents reported that the VISIA
      analysis helped them understand their initial concern. 86% noted that the VISIA
      brought other skin problems to their attention. 100% of the subjects responded
      that they would recommend VISIA analysis to others. 62% of subjects responded
      that they would prefer to go to a practice with a VISIA system in comparison to a
      practice without VISIA. CONCLUSION: The VISIA Complexion Analysis System is a
      beneficial tool for dermatology and aesthetic practices with the potential to aid
      in patient education.

PMID- 25607695
TI  - Muscle weakness in treatment of palmar hyperhidrosis with botulinum toxin type a:
      can it be prevented?
AB  - BACKGROUND: Palmar hyperhidrosis is a chronic disorder, resistant to conventional
      treatment. Clinical studies suggest the effectiveness of botulinum toxin A in the
      treatment of primary palmar hyperhidrosis. OBJECTIVE: To evaluate the efficacy of
      botulinum toxin A in the therapy of palmar hyperhidrosis and the frequency of
      incurred muscle weakness. MATERIALS AND METHODS: Four hundred seventy-four
      patients with palmar hyperhidrosis were enrolled in the study. The Hyperhidrosis
      Disease Severity Scale (HDSS) and the Minor-iodine starch test were chosen to
      assess the disease severity. In addition, a physician's global assessment scale
      was used to evaluate the effectiveness of the treatment with BTX-A. RESULTS:
      There were 312 females and 162 males aged 19-48 (mean 29 years). The improvement
      following the injection at two weeks and at one, three, six and nine months, as
      evaluated by physicians, was 82%, 83%, 74%, 48% and 28%, respectively. Two
      hundred and seventy five patients reported local pain and muscle weakness
      occurred in 102 patients. CONCLUSIONS: BTX-A led to the reduction of disease
      severity while transient side effects were reported.

PMID- 25607696
TI  - Nonablative 1927 nm fractional resurfacing for the treatment of facial
      photopigmentation.
AB  - BACKGROUND: Long-term exposure to sunlight, including ultraviolet A and B,
      produces signs associated with photoaging and photodamage, including laxity and
      discoloration of the skin. Initial laser treatment for dyspigmentation included
      the use of ablative lasers, followed by Q-switched lasers and more recently
      fractional lasers. OBJECTIVE: We investigated the safety and efficacy of a
      fractionated 1927nm non-ablative thulium laser for the treatment of photo-induced
      pigmentation. METHODS: Prospective multi-center study of subjects with clinically
      identifiable photopigmentation. The study protocol was approved by BioMed
      Institutional Review Board (San Diego, CA). Subjects received two treatments with
      a non-ablative 1927nm fractionated thulium laser (Fraxel Dual 1550/1927 Laser
      System, Solta, Hayward CA), energy level of 10mJ, coverage of 40% and 4-6 passes.
      Subject pain, erythema and edema were recorded immediately after treatment. Two
      dimensional photography was obtained before each treatment and at one and three
      month follow up visits. Independent blinded physician assessment was performed
      evaluating overall improvement in appearance as well as pigment specific
      improvement. RESULTS: Forty men and women, ages 30 to 80 years, Fitzpatrick skin
      types I-IV, with photo-induced facial pigmentation were enrolled and treated, and
      39 completed the three month follow up visit. Mean pain sensation for subjects
      during laser treatments was reported to be 4.3 on a 10-point scale. Mean scores
      for erythema, edema, and skin roughness throughout all treatments indicated
      moderate erythema, mild edema and mild skin roughness. Assessment of overall
      improvement was graded as moderate to very significant in 82% of subjects at one
      month and in 69% of subjects at three months after the second treatment.
      Assessment of lentigines and ephelides demonstrated moderate to very significant
      improvement in approximately 68% of subjects at the one month and in 51% of
      subjects at three months after the second treatment. Independent blinded
      physician assessment of randomized photography also demonstrated a durable
      response at three month follow up visit. Treatment was well tolerated and no
      serious adverse events related to treatment were observed or reported. Study
      limitations included a limited number of male subjects, lack of Fitzpatrick skin
      types V and VI, and decrease in improvement at 3 months post-treatment.
      CONCLUSIONS: Two treatments with a 1927nm non-ablative fractionated thulium laser
      produced moderate to marked improvement in overall appearance and pigmentation
      with high patient satisfaction. The response to treatment was maintained at one
      and three months follow up.

PMID- 25607697
TI  - Clinical evaluation of a non-ablative 1940 nm fractional laser.
AB  - BACKGROUND AND OBJECTIVES: Non-ablative fractional lasers cause little down-time,
      however, some patients want more noticeable results with fewer treatments. The
      1940 nm wavelength matches one of the water absorption peaks in the mid infrared
      band of electromagnetic energy. The skin absorption is much stronger than other
      non-ablative wavelengths (1410-1550 nm) and weaker than ablative wavelengths
      (Er:YAG or CO2). The objective of this study was to characterize clinical
      efficacy using this technology to treat photodamaged skin in human subjects.
      MATERIALS AND METHODS: Under an IRB approved study, eleven subjects with facial
      photodamage (1 male and 10 female) were enrolled and completed the study. The
      fractional 1940 nm laser was comprised of a thulium rod pumped by a pulsed
      alexandrite laser. The fractional patterns were generated by four separate
      handpieces (two dot (0.48mm and 0.76mm dot-to-dot distance or pitch) and two grid
      geometries) whereby a larger beam was broken up into smaller microbeams by a
      microlens system or reflective square grids. The low -pitch circular dot array
      handpiece, which is used most frequently, has a macro-spot size of 12 mm and a
      total applied energy of approximately 2-5 J (~ 4-10 mJ per beamlet). Contact skin
      cooling (5-20degC) was provided via a sapphire window at the distal end of
      handpiece. Pulses from the dot handpieces were applied with 20% overlap. The
      microspot size for the dot handpieces was ~ 0.2-0.3 mm. The two grid pattern
      handpieces included 0.4 mm wide lines with 45% and 0.7 mm wide lines with 65%
      coverage. Each subject received 3 full-face treatments 4-6 weeks apart.
      Anesthesia was achieved by 5% lidocaine cream and a cold air chiller. Typical
      treatments were carried out with two passes. Outcome assessments included changes
      in pigment, rhytides, laxity, elastosis, and texture, using a diffuse
      pigmentation scale and the Alexiades-Armenakas Comprehensive Grading Scale of
      Rhytides, Laxity, and Photodamage. Photographs of each patient from prior to
      treatment, and 3 months after treatment were analyzed by 3 blinded physician
      raters. A paired t-test was applied for each category comparing the pre treatment
      and 3-month post treatment results. RESULTS: Three months after the final
      treatment, (a) mean pigment improvement was 21.1%, (b) rhytides were reduced by
      14.3%, (c) laxity was reduced by 8.9%, elastosis was reduced by 22.3%, and (e)
      texture scores were unchanged. Reductions in pigmentation, rhytides, and
      elastosis were statistically significant (P<= 0.05). Clinical downtime was 3-5
      days. Pain was variable (mean of 2.8/10) and side effects included two cases of
      mild focal vesiculation. No long-term side effects were noted. Histological
      analysis showed focal damage that extended about 200 MUm deep to the surface.
      CONCLUSION: The 1940nm thulium laser is safe, well tolerated, and results in
      reduced downtime compared to traditional resurfacing. The study demonstrated that
      the 1940 nm thulium laser could achieve injury patterns capable of skin
      rejuvenation.

PMID- 25607698
TI  - Radiofrequency: an update on latest innovations.
AB  - As the aging population in our society continues to grow, new technologies and
      procedures promising a more youthful appearance are continuously sought. The
      utilization of radiofrequency technology remains a novel method for the treatment
      of many aesthetic and medical dermatological indications. Innovative applications
      are constantly identified, expanding treatment options for various patient
      concerns including aging of the hands, cellulite, non-invasive lipolysis, and
      postpartum skin laxity. Non-invasive treatments are ideal for busy patients
      seeking minimal recovery time and so called lunch-time procedures. Furthermore,
      new developments in treatment devices enhance efficacy while decreasing patient
      discomfort.

PMID- 25607699
TI  - A focused monopolar radiofrequency causes apoptosis: a porcine model.
AB  - BACKGROUND: The purpose of this study was to demonstrate the effect of monopolar,
      focused radiofrequency (RF) with embedded cooling on subcutaneous skin
      structures. Specifically, the study was to prove that the monopolar RF with
      cooling can selectively heat fat, causing disintegration of adipocytes and
      programmed cell death (apoptosis) of the subcutaneous fat cells. METHODS: A non
      invasive monopolar RF device with cooling (Exilis Elite, BTL Industries,
      Framingham, MA) was used to reduce abdominal fat in a porcine model. The study
      was done on 3 Vietnamese pigs in a certified veterinary facility. The treatment
      was delivered to an area the size of 20 x 10cm. The treatment duration was 11
      minutes, 30 seconds. Biopsy samples were taken before the first treatment, 1 hour
      post each treatment, as well as 8 and 20 hours post each treatment. Programmed
      cell death (apoptosis) was monitored using the TUNEL method. The temperature was
      measured on the skin surface by an infrared thermal imager and built-in IR
      thermometer, and by an internal probe inserted into various depths of the
      subcutaneous layer. The internal probe placement was monitored by diagnostic
      ultrasound examination. RESULTS: The temperature in the treated adipose tissue
      was higher compared to the skin surface temperature. The average temperature
      gradient observed was 3.1 degrees C. Due to the temperature gradient the skin
      surface remained intact, while subcutaneous layers showed significant changes.
      The TUNEL method proved large-scale apoptosis of fat cells after each treatment.
      The apoptotic index increased from 7% before the first treatment to an average of
      53.4%, 39.6%, 40.2%, and 44.7% respectively for each treatment. In the three
      month follow up the apoptotic index dropped back to 11.7%. Histology, blood
      biochemistry and hematology samples showed mild to no signs of inflammation in
      the treated area. CONCLUSION: The study has shown that use of monopolar, focused
      radiofrequency can induce substantial apoptotic process in a porcine model. The
      data suggests that the monopolar, focused radiofrequency device can be used for
      reduction of fat and body shaping.

PMID- 25607700
TI  - Home-based wrinkle reduction using a novel handheld multisource phase-controlled
      radiofrequency device.
AB  - BACKGROUND: In the last decade, energy-based aesthetic treatments, using light,
      radiofrequency (RF), and ultrasound, have gained scientific acceptance as safe
      and efficacious for non-invasive treatment for aesthetic skin disorders. The
      phase-controlled multisource radiofrequency technology (3DEEPTM), which is based
      on the simultaneous use of multiple RF generators, was proven to allow
      significant pigment-independent dermal heating without pain or the need of
      epidermal cooling. This study was performed in order to evaluate the efficacy and
      safety of a new handheld device delivering multisource radiofrequency to the skin
      for wrinkle reduction and skin tightening in the home setting. PATIENTS AND
      METHODS: A total of 69 participants (age 54.3 years +/- 8.09; age range 37-72
      years) were enrolled in the study after meeting all inclusion/exclusion criteria
      (100%) and providing informed consent. Participants were provided with the tested
      device together with a user manual and treatment diary, to perform independent
      treatments at home for 4 weeks. The tested device, (NewaTM, EndyMed Medical,
      Cesarea, Israel) emits 12 W of 1Mhz, RF energy through six electrodes arranged in
      a linear fashion. Independent control of RF polarity through each one of the 6
      electrodes allows significant reduction of energy flow through the epidermis with
      increased dermal penetration. Participants were instructed to perform at least 5
      treatments a week, for one month. Four follow-up visits were scheduled (once a
      week) during the period of independent treatments at home, following 4 weeks of
      home treatments, 1 month follow-up visit (1 month after treatment end) and at 3
      months follow-up (3 months following treatment end). Analysis of pre-and post
      treatment images was conducted by three uninvolved physicians experienced with
      the Fitzpatrick Wrinkle and Elastosis Scale. Fitzpatrick Wrinkle and Elastosis
      score of each time point (4 weeks following home use treatments; 1 month follow
      up, 3 months follow-up) was compared to baseline. Participants were asked a
      series of questions designed to explore usability concerns and level of
      satisfaction regarding the device use and subjective efficacy. RESULTS:
      Altogether, 62 subjects completed the study course and follow-up visits. No
      unexpected adverse effects were detected or reported throughout the independent
      treatment. All study participants did not experience any difficulties while
      operating the tested device for independent wrinkle reduction treatments.
      Photographic analysis of pre- and post-one month of independent home use
      treatments, and one and three months follow-up after end of treatment course, was
      conducted by three uninvolved board certified dermatologists. Analysis of results
      revealed improvement (downgrade of at least 1 score according to the Fitzpatrick
      scale) in 91.93%, 96.77%, and 98.39% of study subjects (according to the first,
      second, and third reviewer, respectively). Results were found to be statistically
      significant. The majority of study participants were very satisfied from the
      results of the independent treatment using the tested device for wrinkle
      reduction.

PMID- 25607701
TI  - Pulsed dye laser therapy for molluscum contagiosum: a systematic review.
AB  - BACKGROUND: Molluscum contagiosum (MC) is a benign contagious viral skin
      infection that typically resolves without treatment within months. For cases
      where treatment is recommended or requested, a number of options are available.
      Over the last 2 decades, a number of case reports and case series have described
      cases of MC lesions that were successfully treated with pulsed dye laser (PDL);
      however, a review of these studies has not been reported in the dermatologic
      literature. OBJECTIVES: To review the use of PDL for the treatment of MC.
      MATERIALS AND METHODS: A search of the National Library of Medicine's PubMed
      Database and the SCOPUS Database was performed to find articles that detailed the
      treatment of MC with PDL. RESULTS: Eight articles met criteria for inclusion in
      this review. These articles represented 161 patients with over 4200 MC lesions
      that were treated with PDL. Each article was reviewed and summarized in a table.
      LIMITATIONS: The main limitation of this review is the small number of published
      studies, which reflects the importance of this review of the dermatology
      literature. CONCLUSIONS: PDL offers a novel and effective treatment for MC.
      However, the articles reviewed herein suggest PDL is a safe, effective, quick and
      well-tolerated treatment for clearing MC lesions that does not cause scarring or
      permanent pigment change.

PMID- 25607702
TI  - Treatment of facial actinic keratoses with aminolevulinic acid photodynamic
      therapy (ALA-PDT) or ingenol mebutate 0.015% gel with and without prior treatment
      with ALA-PDT.
AB  - OBJECTIVE: This randomized, 3-group study compared the efficacy and tolerability
      of 3 treatment modalities for facial actinic keratoses. METHODS: Twenty-four
      healthy adult male and female subjects who had 4 to 8 clinically visible and
      discrete actinic keratoses on the face in a contiguous 25cm2 treatment area.
      Subjects were randomized into one of three treatment groups: 2 treatments with 5
      aminolevulinic acid (ALA) and photodynamic therapy (PDT), 1 ALA-PDT treatment and
      1 course of ingenol mebutate (ingenol mebutate) 0.015% gel daily for 3
      consecutive days, or 1 course of ingenol mebutate gel alone. Actinic keratoses in
      the treatment field were counted at the baseline visit, and at the completion of
      the study (day 57 or day 71). At the site of application, local site reactions
      were graded at each visit. RESULTS: Subjects in the two ALA-PDT treatment group
      had a 97.5% mean reduction (P<0.00001) from the number of baseline actinic
      keratosis; ALA-PDT plus ingenol mebutate gel group had an 86.7% mean reduction
      (P<0.00001); while subjects in the ingenol mebutate gel alone group had a 91.7%
      mean reduction from the number of baseline actinic keratoses. The peak composite
      LSR score was 4.625 for the ALA-PDT group, 10.375 for the ALA-PDT followed by
      ingenol mebutate gel group, and 12.625 for the ingenol mebutate gel alone group
      (P=0.0004 and 0.001, respectively). CONCLUSION: ALA-PDT, ingenol mebutate gel,
      and a combination of the two treatment modalities are successful topical
      therapies for the reduction of actinic keratoses on the face. The group of
      subjects receiving 2 consecutive treatments with ALA-PDT, compared to treatment
      with ingenol mebutate gel alone or sequentially after one course of ALA-PDT had a
      significantly lower mean composite LSR score and a non-significant trend for
      greater efficacy.

PMID- 25607703
TI  - Antibiotic resistance: shifting the paradigm in topical acne treatment.
AB  - INTRODUCTION: Multiple topical therapies are available for mild to moderate acne
      vulgaris. The role of antibiotics and their resistance in the treatment of acne
      was reviewed by an expert panel of dermatologists who practice in Canada.
      METHODS: Prior to the consensus meeting, the panel members filled out a survey on
      their current practice using topical treatment for acne. A literature review was
      carried out using information obtained from PubMed, Cochrane Library, Medline,
      and EMBASE. During a consensus meeting organized at the Spring Dermatology Update
      on April 27, 2014 in Toronto, ON, the panel had a blind vote on the issues at
      hand. RESULTS: The panel reached consensus on: 1) Antibiotics are an integral
      part of acne treatment not only due to their antibiotic effect but also by their
      anti-inflammatory action. 2) Oral antibiotics should be used for a short period
      of time if possible. 3) Topical antibiotics should not be used in monotherapy. 4)
      Retinoids are effective in reducing antibiotic resistance. 5) A benzoyl peroxide
      wash is as effective as topical benzoyl peroxide in reducing antibiotic
      resistance. 6) Therapy needs to be re-evaluated in 6-8 weeks versus 12 weeks. The
      recommendations given by the panel are to be disseminated to both general
      practitioners and dermatologists. CONCLUSION: For mild to moderate acne
      treatment, topical antibiotics in monotherapy are not to be used but may be
      combined with a retinoid or BPO to safely achieve more successful outcomes.

PMID- 25607704
TI  - Microbiome of affected and unaffected skin of patients with atopic dermatitis
      before and after emollient treatment.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disorder that results in
      areas of dry, itchy skin. Several cultivation-dependent and -independent studies
      have identified changes in the composition of microbial communities in these
      affected areas over time and when compared to healthy control individuals.
      However, how these communities vary on affected and unaffected skin of the same
      individual, and how these communities respond to emollient treatment, remains
      poorly understood. Here we characterized the microbial communities associated
      with affected and unaffected skin of 49 patients with AD before and after
      emollient treatment using high-throughput sequencing of the 16S rRNA gene. We
      found that microbial diversity and community composition was different between
      affected and unaffected skin of AD patients prior to treatment. Differences were
      driven primarily by the overabundance of Staphylococcus species on affected skin
      and a corresponding decrease in bacterial diversity. After 84-days of emollient
      treatment, the clinical symptoms of AD improved in 72% of the study population.
      Microbial communities associated with affected skin of these treatment responders
      more closely resembled unaffected skin after treatment as indicated by increased
      overall diversity and a decrease in the abundance of Staphylococcus species.
      Interestingly, Stenotrophomonas species were significantly more abundant in the
      communities of 'responders', suggesting a possible role in restoration of the
      skin microbiome in patients with AD. We demonstrated that the comparison of
      affected and unaffected skin from the same individual provides deeper insight
      into the bacterial communities involved in the skin dysbiosis associated with AD.
      These data support the importance of emollients in the management of AD although
      future studies should explore how emollients and other treatments help to restore
      skin dysbioses.

PMID- 25607705
TI  - Real-life treatment profile of calcipotriene and betamethasone dipropionate
      topical suspension in patients with psoriasis vulgaris.
AB  - BACKGROUND: Treatment with calcipotriene plus betamethasone dipropionate (CBD)
      fixed-combination topical suspension has been shown to be effective and well
      tolerated in patients with psoriasis vulgaris. AIM: To document experiences with
      CBD topical suspension in a US clinical dermatology setting using patient
      reported outcomes (PROs). METHODS: In total, 147 patients were enrolled in this 8
      week, prospective, noninterventional, multicenter, one-arm study. Data were
      collected at baseline and week 8 at the office, and at one time at home (week 2).
      PROs were assessed using the Dermatology Life Quality Index (DLQI), Patient's
      Global Assessment of disease severity (PtGA) using a 5-point Likert scale,
      patient-reported level of itching using a 0-100 graduated visual analog scale,
      and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Treatment
      adherence and adverse events (AEs) were assessed at week 8. RESULTS: After 8
      weeks of treatment, DLQI score significantly improved compared with baseline (
      5.5 +/- 5.93; P<.0001), starting as early as week 2 (-4.2 +/- 5.28; P<.0001). The
      level of itching was significantly reduced from baseline to week 2 (-19% +/-
      25.94%; P<.0001) and week 8 (-28.6% +/- 29.14%; P<.0001). The percentage of
      patients with "controlled disease" (PtGA score of "clear" or "very mild") was
      34.1% at week 2 and 60.2% at week 8. At the end of treatment, mean TSQM-9 scores
      for effectiveness, convenience, and satisfaction domains ranged from 68 to 74.
      Patients reported the need to use CBD topical suspension for an average of 53.62
      +/- 8.05 days. Treatment-emergent AEs occurred in 3 patients. CONCLUSION: The
      results of this noninterventional study are consistent with previously reported
      data from interventional trials and suggest that treatment with CBD topical
      suspension is efficacious and well tolerated and improves quality of life in
      patients with psoriasis vulgaris.

PMID- 25607707
TI  - Transungual delivery of efinaconazole: its deposition in the nail of
      onychomycosis patients and in vitro fungicidal activity in human nails.
AB  - BACKGROUND: Effective transungual delivery of topical antifungal agents in
      onychomycosis has been hampered by poor nail permeation. To be effective they
      must have antifungal efficacy, and effectively permeate through the dense
      keratinized nail plate to the site of infection in the nail bed and nail matrix.
      The therapeutic efficacy of efinaconazole topical solution, 10% has been
      established in two phase 3 clinical trials in distal lateral subungual
      onychomycosis. OBJECTIVE: To investigate the transungual delivery of
      efinaconazole in onychomycosis patients and its fungicidal activity in the
      toenail. METHODS: Concentrations of efinaconazole were determined as part of a
      multi-center, open label study in forty onychomycosis patients following repeated
      application of efinaconazole topical solution, 5% and 10% to the toenails over 28
      days, with a 2-week follow-up. Fungicidal activity against T. rubrum in the
      ventral layer of human nails was determined using an in vitro human nail
      infection model (ChubTur(r)). RESULTS: Efinaconazole concentrations in the nail
      were four orders of magnitude higher than MIC values of efinaconazole against
      dermatophytes. Further, nail drug concentrations were not influenced by the
      presence of disease or nail thickness, and maintained at high antifungal levels
      post-treatment. Efinaconazole was effective in reducing fungal viability,
      suggesting that sufficient amounts of efinaconazole were being delivered into the
      ventral layer of the nail plate.<BR /> CONCLUSIONS: Effective transungual
      delivery of efinaconazole was demonstrated. The high efinaconazole concentrations
      in patient toenails and fungicidal activity in vitro potentially contribute to
      the clinical efficacy reported in phase 3 studies.

PMID- 25607708
TI  - Access of efinaconazole topical solution, 10%, to the infection site by spreading
      through the subungual space.
AB  - OBJECTIVE: To evaluate the ability of efinaconazole vehicle to reach the site of
      toenail onychomycosis by spreading through the subungual space between the nail
      plate and nail bed. Lacquer-based vehicles are primarily limited to application
      on the nail plate and dependent on nail plate permeation. METHODS: 11 patients
      (mean age 48.5 years) were entered with clinically determined onychomycosis.
      Presence of fungal infection was confirmed by KOH testing in eight patients. Two
      separate applications of vehicle (with fluorescein incorporated for better
      visualization) were applied at the hyponychium, avoiding application to the
      exterior nail plate surface. Affected nails were later clipped to allow
      examination of the nail bed and further examination of the underside of the nail.
      Spread of formulation was assessed under visible and UV light conditions by
      photographing target toenails after vehicle application, and after nail clipping.
      RESULTS: Assessments under both visible and UV light indicated that the vehicle
      had spread into the subungual space, with deposition of flourescein wherever
      vehicle had reached, including in the nail bed. Nail clippings also indicated
      deposition to the underside of the nail plate. LIMITATIONS: The relative
      contributions of spreading into the subungual space, or permeation through the
      nail plate to the efficacy of efinaconazole topical solution, 10% in treating
      onychomycosis were not assessed. CONCLUSIONS: This study suggests that the
      vehicle developed for efinaconazole topical solution, 10%, when applied at the
      hyponychium, spreads into the subungual space between the nail plate and nail
      bed, reaching the site of infection.

PMID- 25607706
TI  - Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating
      inflammatory lesions of rosacea: results of two 40-week controlled, investigator
      blinded trials.
AB  - Papulopustular rosacea (PPR) is characterized by facial erythema and inflammatory
      lesions believed to be primarily caused by dysregulation of the innate immune
      system. More recent evidence also suggests that Demodex folliculorum mites may
      contribute to the etiology of PPR. Ivermectin (IVM) 1% cream is a novel topical
      treatment developed to treat PPR. Two phase 3 trials have demonstrated that IVM
      1% cream was significantly better than vehicle at investigator global assessment
      (IGA) success rate and lesion reductions and that it was safe and well tolerated.
      Two 40-week extension studies of those trials were conducted to assess the long
      term safety of IVM 1% cream vs azelaic acid (AzA) 15% gel. Subjects originally
      treated with IVM 1% continued on IVM 1% and those originally treated with vehicle
      switched to AzA 15% gel. IVM 1% cream was safe throughout the study with a lower
      incidence of related adverse events (AEs) compared to AzA 15% gel. No subjects in
      the IVM 1% cream group discontinued either study due to a related AE. IVM 1% also
      continued to be efficacious during the 40-week extension studies as the
      percentage of subjects with IGA scores of clear or almost clear was higher at the
      end of the study compared to baseline. The results of these 40-week extension
      studies support the use of IVM 1% cream as a long-term therapy for PPR as IVM 1%
      cream was shown to be safe and effective for up to 52 weeks of total treatment.

PMID- 25607709
TI  - A single-blinded randomized controlled study to assess the efficacy of twice
      daily application of sinecatechins 15% ointment when used sequentially with
      cryotherapy in the treatment of external genital warts.
AB  - OBJECTIVE: To evaluate the efficacy of sequential therapy of cryotherapy and
      sinecatechins 15% ointment BID versus cryotherapy alone in treatment of external
      genital warts (EGW). METHODS: Forty-two subjects with at least two EGW lesions
      underwent cryotherapy to all lesions. One week following cryotherapy, subjects
      were randomized 1:1 to receive either no additional treatment or treatment with
      sinecatechins 15% ointment BID up to 16 weeks or until complete clearance. The
      total number of visible baseline and new EGW were recorded at each visit.
      Subjects were followed for a total of 65 weeks post-treatment. RESULTS: There was
      a significant reduction in mean number of lesions from baseline after 16 weeks of
      treatment in the cryotherapy-sinecatechins ointment group compared to cryotherapy
      alone (-5.0 lesions vs -2.1 lesions respectively, P=0.07). CONCLUSION:
      Cryotherapy plus sinecatechins 15% ointment BID resulted in a significant
      improvement in the reduction of EGW compared to cryotherapy alone.
      Clinicaltrials.gov registration identifier: NCT02147353.

PMID- 25607710
TI  - Efficacy of botulinum neurotoxin type A for treating recalcitrant plaque
      psoriasis.
AB  - Use of botulinum neurotoxin A (BoNTA) for treating inflammatory skin disease is
      an underexplored area in medical dermatology. Preclinical mouse studies have
      demonstrated efficacy of abobotulinumtoxinA in improving psoriasiform skin
      inflammation. We describe sustained local clearance of a psoriasis plaque in a
      patient following a single off-label injection of intradermal abobotulinumtoxinA.
      BoNTA may offer a novel therapeutic approach for treating recalcitrant plaque
      psoriasis. Case reports and anecdotal evidence suggests that onabotulinumtoxinA
      may be useful for treating inverse psoriasis.1,2 We previously reported an
      improvement in skin phenotype in a preclinical mouse model following a single
      intradermal injection of abobotulinumtoxinA.3 Here we present a patient case
      report demonstrating efficacy of abobotulinumtoxinA in reversing plaque
      psoriasis.

PMID- 25607711
TI  - A case of new onset keratosis pilaris after discontinuation of erlotinib.
AB  - IMPORTANCE: Keratosis pilaris and keratosis pilaris-like eruptions have been
      reported in association with RAF inhibitors sorafenib and vemurafenib. We
      describe herein what is to our knowledge the first reported case of new onset
      keratosis pilaris after discontinuation of EGFR inhibitor erlotinib.
      OBSERVATIONS: A 60 year-old female with stage IV lung cancer was treated with
      erlotinib (100 mg/d). The patient elected to discontinue erlotinib after four
      years secondary to adverse systemic reactions. However, five months later small,
      monomorphic, rough, folliculocentric papules with surrounding mild erythema
      characteristic of keratosis pilaris were noted on upper back and arms.
      CONCLUSIONS AND RELEVANCE: This serves as the first documented case of new onset
      keratosis pilaris in a patient after discontinuation of erlotinib. We report the
      present case to show the possible association of keratosis pilaris with not only
      RAF inhibitors, but also the EGFR inhibitor erlotinib. Further investigation will
      determine whether this is a class effect with other systemic EGFR inhibitors.

PMID- 25607712
TI  - Repurposing of drugs for dermatologic applications: five key medications.

PMID- 25607715
TI  - The structures of hexadecylamine films adsorbed on iron-oxide surfaces in
      dodecane and hexadecane.
AB  - Molecular-dynamics simulations are used to gain insights on recent sum-frequency
      spectroscopy and polarised neutron reflectometry measurements of the structure of
      hexadecylamine films adsorbed on iron-oxide surfaces in dodecane and hexadecane.
      Simulations were carried out under quiescent and high-shear conditions. Mass
      density profiles, molecular-height and molecular-orientation probability
      distribution functions, and in-layer radial distribution functions were
      calculated. The simulation results show that at high surface coverage, the film
      thickness is about 15 A, and that the molecules are mainly pointing upwards from
      the surface at an angle of 40-50 degrees . The results are compared critically
      against published experimental results, and the agreement is found to be good.
      The in-layer ordering of the hexadecylamine head-group atoms is found to be
      dictated by the crystalline structure of the iron-oxide surface, but this
      influence rapidly diminishes along the molecular backbone. The tail-group atoms
      show almost no positional ordering. Finally, an example calculation of the
      kinetic friction coefficient under high-shear conditions is presented. The
      lateral (friction) force is measured as a function of the normal (applied) force,
      and the kinetic friction coefficient is determined to be about 0.09, which is
      typical for this kind of system. 

PMID- 25607713
TI  - MiR-101 sensitizes human nasopharyngeal carcinoma cells to radiation by targeting
      stathmin 1.
AB  - Radioresistance remains a major problem in the treatment of patients suffering
      from nasopharyngeal carcinoma (NPC). A better understanding of the mechanisms
      involved in the induction of radioresistance may provide strategies to improve
      NPC patients' response to therapy. The present study aimed to investigate the
      effect of microRNA (miR)-101 on the radioresistance of NPC cells. Analysis of miR
      101 expression levels indicated that miR-101 was downregulated in NPC cell lines.
      Furthermore, ectopic expression of miR-101 suppressed cell proliferation and
      enhanced radiosensitivity of NPC cells. Stathmin 1 (STMN1) was additionally
      verified as a direct functional target of miR-101, which was found to be involved
      in cell viability, radioresistance and radiation-induced autophagy of NPC cells.
      In conclusions, the results of the present study suggested that the identified
      miR-101/STMN1 pathway contributed to the elucidation of the mechanisms of
      radioresistance in human NPC and that it may represent a potential therapeutic
      target.

PMID- 25607716
TI  - Rennet Coagulation and Cheesemaking Properties of Thermally Processed Milk:
      Overview and Recent Developments.
AB  - Thermally induced changes in milk proteins and minerals, particularly
      interactions among caseins and denatured whey proteins, influence important
      properties of dairy products in both positive and negative ways. Whereas the
      extensive protein connectivity and increased water-holding capacity resulting
      from such heat-induced protein modification account for the much desired firmness
      of acid gels of yogurt, thermal processing, on the other hand, severely impairs
      clotting and adversely affects the cheesemaking properties of rennet-coagulated
      cheeses. In technological terms, the principal ongoing challenge in the cheese
      industry is to take advantage of the water-holding capacity of thermally
      aggregated whey proteins without compromising the rennetability of cheese milk or
      the textural and functional attributes of cheese. Including some recent data from
      the authors' laboratory, this paper will discuss important aspects and current
      literature on the use of thermally processed milk in the production of rennet
      coagulated cheeses and also some of the potential alternatives available for
      inclusion of whey proteins in cheese, such as the addition of microparticulated
      whey proteins to cheese milk. 

PMID- 25607717
TI  - Social integration and health insurance status among African American men and
      women.
AB  - Using 2010 national data, we investigate the relationship between social
      integration and health insurance for African American adults. During the previous
      year 21.6% of men and 19.8% of women lacked continuous health insurance. The
      effect of marital status, income, and employment on insurance coverage differed
      by age and gender. Additionally, frequency of church attendance was positively
      associated with continuous health insurance for women aged 51-64.
      Spiritual/religious identity was marginally associated with insurance status for
      men aged 36-50. As provisions of the Affordable Care Act take effect,
      implementation programs should expand enrollment efforts to include the conjugal
      unit and the church. 

PMID- 25607718
TI  - Dual-task interference in evaluative conditioning: Similarity matters!
AB  - Evaluative conditioning (EC) refers to changes in liking that are due to the
      pairing of stimuli. Although the question of whether a secondary task can
      interfere with the occurrence of EC is of great theoretical relevance, previous
      research has not obtained a consistent pattern of results. Whereas in some
      studies EC remains intact under dual-task conditions, in others a secondary task
      resulted in reduced or diminished EC. In order to reconcile these inconsistent
      findings, we hypothesized that dual-task interference in EC depends on the
      similarity of demands incurred by processing the stimuli used in the conditioning
      procedure and the secondary task. Specifically, we assumed that interference only
      occurs when similar verbal or visuospatial demands are imposed. In order to test
      this hypothesis, we investigated the occurrence of EC under conditions of a
      demanding 3-back working memory task while using either orthographic or pictorial
      stimuli to manipulate verbal and visuospatial processing demands, respectively.
      Relative to conditions using dissimilar types of stimuli, we found that the 3
      back task interfered with the occurrence of EC only when the same types of
      stimuli were used. The implications for the underlying processes of EC are
      discussed. 

PMID- 25607719
TI  - Alterations in Gas Exchange and Oxidative Metabolism in Rice Leaves Infected by
      Pyricularia oryzae are Attenuated by Silicon.
AB  - Rice blast, caused by Pyricularia oryzae, is the most important disease in rice
      worldwide. This study investigated the effects of silicon (Si) on the
      photosynthetic gas exchange parameters (net CO2 assimilation rate [A], stomatal
      conductance to water vapor [gs], internal-to-ambient CO2 concentration ratio
      [Ci/Ca], and transpiration rate [E]); chlorophyll fluorescence a (Chla)
      parameters (maximum photochemical efficiency of photosystem II [Fv/Fm],
      photochemical [qP] and nonphotochemical [NPQ] quenching coefficients, and
      electron transport rate [ETR]); concentrations of pigments, malondialdehyde
      (MDA), and hydrogen peroxide (H2O2); and activities of superoxide dismutase
      (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR),
      and lypoxigenase (LOX) in rice leaves. Rice plants were grown in a nutrient
      solution containing 0 or 2 mM Si (-Si or +Si, respectively) with and without P.
      oryzae inoculation. Blast severity decreased with higher foliar Si concentration.
      The values of A, gs and E were generally higher for the +Si plants in comparison
      with the -Si plants upon P. oryzae infection. The Fv/Fm, qp, NPQ, and ETR were
      greater for the +Si plants relative to the -Si plants at 108 and 132 h after
      inoculation (hai). The values for qp and ETR were significantly higher for the 
      Si plants in comparison with the +Si plants at 36 hai, and the NPQ was
      significantly higher for the -Si plants in comparison with the +Si plants at 0
      and 36 hai. The concentrations of Chla, Chlb, Chla+b, and carotenoids were
      significantly greater in the +Si plants relative to the -Si plants. For the -Si
      plants, the MDA and H2O2 concentrations were significantly higher than those in
      the +Si plants. The LOX activity was significantly higher in the +Si plants than
      in the -Si plants. The SOD and GR activities were significantly higher for the 
      Si plants than in the +Si plants. The CAT and APX activities were significantly
      higher in the +Si plants than in the -Si plants. The supply of Si contributed to
      a decrease in blast severity, improved the gas exchange performance, and caused
      less dysfunction at the photochemical level. 

PMID- 25607720
TI  - Population Structure of Pythium irregulare, P. ultimum, and P. sylvaticum in
      Forest Nursery Soils of Oregon and Washington.
AB  - Pythium species are important soilborne pathogens occurring in the forest nursery
      industry of the Pacific Northwest. However, little is known about their genetic
      diversity or population structure and it is suspected that isolates are moved
      among forest nurseries on seedling stock and shared field equipment. In order to
      address these concerns, a total of 115 isolates of three Pythium species (P.
      irregulare, P. sylvaticum, and P. ultimum) were examined at three forest
      nurseries using simple sequence repeat (SSR) and amplified fragment length
      polymorphism (AFLP) markers. Analyses revealed distinct patterns of intraspecific
      variation for the three species. P. sylvaticum exhibited the most diversity,
      followed by P. irregulare, while substantial clonality was found in P. ultimum.
      For both P. irregulare and P. sylvaticum, but not P. ultimum, there was evidence
      for significant variation among nurseries. However, all three species also
      exhibited at least two distinct lineages not associated with the nursery of
      origin. Finally, evidence was found that certain lineages and clonal genotypes,
      including fungicide-resistant isolates, are shared among nurseries, indicating
      that pathogen movement has occurred. 

PMID- 25607721
TI  - Precision of working memory for speech sounds.
AB  - Memory for speech sounds is a key component of models of verbal working memory
      (WM). But how good is verbal WM? Most investigations assess this using binary
      report measures to derive a fixed number of items that can be stored. However,
      recent findings in visual WM have challenged such "quantized" views by employing
      measures of recall precision with an analogue response scale. WM for speech
      sounds might rely on both continuous and categorical storage mechanisms. Using a
      novel speech matching paradigm, we measured WM recall precision for phonemes.
      Vowel qualities were sampled from a formant space continuum. A probe vowel had to
      be adjusted to match the vowel quality of a target on a continuous, analogue
      response scale. Crucially, this provided an index of the variability of a memory
      representation around its true value and thus allowed us to estimate how memories
      were distorted from the original sounds. Memory load affected the quality of
      speech sound recall in two ways. First, there was a gradual decline in recall
      precision with increasing number of items, consistent with the view that WM
      representations of speech sounds become noisier with an increase in the number of
      items held in memory, just as for vision. Based on multidimensional scaling
      (MDS), the level of noise appeared to be reflected in distortions of the formant
      space. Second, as memory load increased, there was evidence of greater clustering
      of participants' responses around particular vowels. A mixture model captured
      both continuous and categorical responses, demonstrating a shift from continuous
      to categorical memory with increasing WM load. This suggests that direct acoustic
      storage can be used for single items, but when more items must be stored,
      categorical representations must be used. 

PMID- 25607722
TI  - Controlling the dopant dose in silicon by mixed-monolayer doping.
AB  - Molecular monolayer doping (MLD) presents an alternative to achieve doping of
      silicon in a nondestructive way and holds potential for realizing ultrashallow
      junctions and doping of nonplanar surfaces. Here, we report the mixing of dopant
      containing alkenes with alkenes that lack this functionality at various ratios to
      control the dopant concentration in the resulting monolayer and concomitantly the
      dopant dose in the silicon substrate. The mixed monolayers were grafted onto
      hydrogen-terminated silicon using well-established hydrosilylation chemistry.
      Contact angle measurements, X-ray photon spectroscopy (XPS) on the boron
      containing monolayers, and Auger electron spectroscopy on the phosphorus
      containing monolayers show clear trends as a function of the dopant-containing
      alkene concentration. Dynamic secondary-ion mass spectroscopy (D-SIMS) and Van
      der Pauw resistance measurements on the in-diffused samples show an effective
      tuning of the doping concentration in silicon. 

PMID- 25607723
TI  - Controlling the energy transfer via multi luminescent centers to achieve white
      light/tunable emissions in a single-phased X2-type Y2SiO5:Eu(3+),Bi(3+) phosphor
      for ultraviolet converted LEDs.
AB  - So far, more than 1000 UV converted phosphors have been reported for potential
      application in white light-emitting diodes (WLEDs), but most of them (e.g.,
      Y2O2S:Eu, YAG:Ce or CaAlSiN3:Eu) suffer from intrinsic problems such as thermal
      instability, color aging or re-absorption by commixed phosphors in the coating of
      the devices. In this case, it becomes significant to search a single-phased
      phosphor, which can efficiently convert UV light to white lights. Herein, we
      report a promising candidate of a white light emitting X2-type
      Y2SiO5:Eu(3+),Bi(3+) phosphor, which can be excitable by UV light and address the
      problems mentioned above. Single Bi(3+)-doped X2-type Y2SiO5 exhibits three
      discernible emission peaks at ~355, ~408, and ~504 nm, respectively, upon UV
      excitation due to three types of bismuth emission centers, and their relative
      intensity depends tightly on the incident excitation wavelength. In this regard,
      proper selection of excitation wavelength can lead to tunable emissions of
      Y2SiO5:Bi(3+) between blue and green, which is partially due to the energy
      transfer among the Bi centers. As a red emission center Eu(3+) is codoped into
      Y2SiO5:Bi(3+), energy transfer has been confirmed happening from Bi(3+) to Eu(3+)
      via an electric dipole-dipole (d-d) interaction. Our experiments reveal that it
      is easily realizable to create the white or tunable emissions by adjusting the
      Eu(3+) content and the excitation schemes. Moreover, a single-phased white light
      emission phosphor, X2-type Y1.998SiO5:0.01Eu(3+),0.01 Bi(3+), has been achieved
      with excellent resistance against thermal quenching and a QE of 78%. At 200 
      degrees C, it preserves >90% emission intensity of that at 25  degrees C.
      Consequent three time yoyo experiments of heating-cooling prove no occurrence of
      thermal degradation. A WLED lamp has been successfully fabricated with a CIE
      chromaticity coordinate (0.3702, 0.2933), color temperature 4756 K, and color
      rendering index of 65 by applying the phosphor onto a UV LED chip. 

PMID- 25607724
TI  - Image overlay solution based on threshold detection for a compact near infrared
      fluorescence goggle system.
AB  - Near infrared (NIR) fluorescence imaging has shown great potential for various
      clinical procedures, including intraoperative image guidance. However, existing
      NIR fluorescence imaging systems either have a large footprint or are handheld,
      which limits their usage in intraoperative applications. We present a compact NIR
      fluorescence imaging system (NFIS) with an image overlay solution based on
      threshold detection, which can be easily integrated with a goggle display system
      for intraoperative guidance. The proposed NFIS achieves compactness, light
      weight, hands-free operation, high-precision superimposition, and a real-time
      frame rate. In addition, the miniature and ultra-lightweight light-emitting diode
      tracking pod is easy to incorporate with NIR fluorescence imaging. Based on
      experimental evaluation, the proposed NFIS solution has a lower detection limit
      of 25 nM of indocyanine green at 27 fps and realizes a highly precise image
      overlay of NIR and visible images of mice in vivo. The overlay error is limited
      within a 2-mm scale at a 65-cm working distance, which is highly reliable for
      clinical study and surgical use.

PMID- 25607725
TI  - Yes-associated protein regulates the growth of human non-small cell lung cancer
      in response to matrix stiffness.
AB  - The Yes-associated protein (YAP) transcriptional coactivator is recognized as a
      crucial regulator of human cancer. However, its involvement in human non-small
      cell lung cancer (NSCLC) in response to physical cues remains unclear. In this
      study, substrates with different rigidity were generated in order to evaluate the
      role of YAP, and its upstream regulators in the Hippo pathway, in the regulation
      of growth of an NSCLC cell line within particular environments. It was shown that
      the expression of the YAP protein in SPCA-1 NSCLC cells was significantly
      increased when cultured on a stiff substrate compared to a soft substrate.
      However, the expression of phospho-YAP protein and large tumor suppressor kinase
      1 (LATS1) were markedly decreased after culturing on the stiff substrate.
      Phosphorylation of YAP by LATS1 leads to cytoplasmic retention of YAP, which
      inhibits its function as a nuclear transcription coactivator. The study also
      found that the stiff substrate promoted the growth of NSCLC cells in vitro, and
      an increase in the transcription levels of Survivin, connective tissue growth
      factor, amphiregulin and Ki67, as well as a decrease in the expression level of
      YAP in the cytoplasm, and adecrease in p-YAP. In conclusion, the findings showed
      that the stiffness of the subcellular matrix altered the behavior of NSCLC cells,
      and that YAP regulated the growth of NSCLC cells in response to matrix stiffness,
      thereby suggesting a role for the Hippo-YAP pathway in the response of NSCLC cell
      growth to specific microenvironments. 

PMID- 25607726
TI  - Emodin attenuates radioresistance induced by hypoxia in HepG2 cells via the
      enhancement of PARP1 cleavage and inhibition of JMJD2B.
AB  - Radioresistance in the tumor and radiotoxicity in the non-tumorous liver
      significantly restrict efficient radiotherapy of hepatocellular carcinoma (HCC).
      It is therefore important to study the radioresistance mechanism and development
      of radiosensitization to optimize the effect of irradiation on cancer cells.
      Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a plant-derived polyphenol,
      possessing anticancer properties. It is known to act as a radiosensitizer in
      human HCC cell lines. The aim of this study was to evaluate the role of emodin in
      radioresistance of human HCC cell lines as well as the underlying
      radiosensitization mechanism. The human HCC cell line (HepG2) was used in this
      study. Four different treatment groups, i.e., no treatment (control), irradiation
      (10 Gy, one fraction), emodin (10 uM), and a combination of irradiation and
      emodin (10 Gy+10 uM) were used for two environmental conditions: hypoxia (1% O2)
      and normoxia (20% O2). The cells were exposed to the respective treatments for 24
      and 72 h. Following the treatment, the cell viability was determined by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the
      radiosensitization mechanism was evaluated by western blotting. The proliferation
      of HepG2 cells was significantly suppressed in the treatment groups under hypoxic
      and normoxic conditions in the following order: combination of irradiation and
      emodin>irradiation only >emodin only. The combination of irradiation and emodin
      induced apoptotic signaling activities such as cleavage of poly (ADP-ribose)
      polymerase (PARP)-1 as well as the downregulation of epigenetic signaling such as
      JMJD1A and JMJD2B. Emodin attenuated radioresistance in the HepG2 cells via
      upregulation of the apoptotic signals and down-regulation of the proliferative
      signals. These results suggested that emodin is a potential candidate for the
      radiosensitization of HCC cells and can aid in identifying novel therapeutic
      strategies for HCC radiotherapy.

PMID- 25607728
TI  - Acceleration of proteolytic activity associated with selection of thiol ligand
      coatings on quantum dots.
AB  - Nanoparticle bioconjugates are attractive probes for measuring the activity of
      hydrolytic enzymes. In these configurations, the localization of multiple copies
      of a hydrolase substrate to a nanoparticle scaffold has been reported to enhance
      apparent activity by factors of 2 to 3 compared to that for equivalent amounts of
      substrate in bulk solution. Here, we studied the effect of surface chemistry on
      protease activity using multivalent QD-peptide substrate conjugates as a model
      system. QDs were coated with cysteine (CYS), glutathione (GSH), dihydrolipoic
      acid (DHLA), or 3-mercaptopropionic acid (MPA) ligands, and thrombin and trypsin
      were used as model proteases. Proteolytic activity was measured for different
      combinations of ligand and protease using Forster resonance energy transfer
      (FRET)-based assays. The highest levels of activity were observed with CYS and
      GSH coatings, and the lowest levels of activity were observed with DHLA and MPA
      coatings. In all cases, proteolytic activity was accelerated compared to that for
      an equivalent amount of substrate in bulk solution, with up to 80- and 65-fold
      increases in the apparent specificity constants for thrombin and trypsin,
      respectively. Thrombin was more strongly affected by the QD surface chemistry,
      with up to a 50-fold variation in its apparent specificity constant between
      ligand coatings, whereas only a 5-fold variation was observed with trypsin. These
      trends were correlated to adsorption of the proteases on the QDs and are
      discussed in the context of the physicochemical properties of both components.
      This work clearly indicates a critical role for the nanoparticle interface in
      mediating substrate turnover and provides some of the strongest support to date
      for a so-called hopping model of activity. 

PMID- 25607727
TI  - Venlafaxine extended-release for depression following spinal cord injury: a
      randomized clinical trial.
AB  - IMPORTANCE: Depression is prevalent and associated with negative outcomes in
      individuals with spinal cord injury (SCI). Antidepressants are used routinely to
      treat depression, yet no placebo-controlled trials have been published in this
      population to our knowledge. OBJECTIVE: To determine the efficacy and
      tolerability of venlafaxine hydrochloride extended-release (XR) for major
      depressive disorder (MDD) or dysthymic disorder in persons with chronic SCI.
      DESIGN, SETTING, AND PARTICIPANTS: Multisite, randomized (1:1), double-blind,
      placebo-controlled Project to Improve Symptoms and Mood After SCI (PRISMS) trial.
      All research staff conducting screening, intervention, and outcome procedures
      were blinded to randomization status. We screened 2536 patients from outpatient
      clinics at 6 SCI treatment centers in the United States and randomized 133
      participants into the trial. Participants were 18 to 64 years old and at least 1
      month after SCI, with MDD or dysthymic disorder. Seventy-four percent of
      participants were male, and participants were on average 40 years old and 11
      years after SCI. Forty-seven percent had cervical injuries, 53.4% had American
      Spinal Injury Association injury severity A (complete injury) SCI, 24.1% had at
      least 2 prior MDD episodes, and 99.2% had current MDD. Common comorbidities
      included chronic pain (93.9%), significant anxiety (57.1%), and history of
      substance dependence (44.4%). INTERVENTIONS: Twelve-week trial of venlafaxine XR
      vs placebo using a flexible-dose algorithm. MAIN OUTCOMES AND MEASURES: The
      Hamilton Depression Rating Scale (HAM-D 17-item version and Maier subscale, which
      focuses on core depression symptoms and excludes somatic symptoms) over 12 weeks.
      RESULTS: Mixed-effects models revealed a significant difference between the
      venlafaxine XR and placebo groups in improvement on the Maier subscale from
      baseline to 12 weeks (treatment effect, 1.6; 95% CI, 0.3-2.9; P = .02) but not on
      the HAM-D 17-item version (treatment effect, 1.0; 95% CI, -1.4 to 3.4; P = .42).
      Participants receiving venlafaxine XR reported significantly less SCI-related
      disability on the Sheehan Disability Scale at 12 weeks compared with placebo
      (treatment effect, 4.7; 95% CI, 1.5-7.8; P = .005). Blurred vision was the only
      significantly more common new or worsening adverse effect in the venlafaxine XR
      group compared with the placebo group over 12 weeks. CONCLUSIONS AND RELEVANCE:
      Venlafaxine XR was well tolerated by most patients and an effective
      antidepressant for decreasing core symptoms of depression and improving SCI
      related disability. Further research is needed to determine the optimal treatment
      and measurement approaches for depression in chronic SCI. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00592384.

PMID- 25607730
TI  - Regioselective direct C-3 arylation of imidazo[1,2-a]pyridines with aryl
      tosylates and mesylates promoted by palladium-phosphine complexes.
AB  - Direct C-3 arylation of imidazo[1,2-a]pyridines with aryl tosylates and mesylates
      has been accomplished by employing palladium(II) acetate associated with SPhos (2
      dicyclohexylphosphino-2',6'-dimethoxybiphenyl) or L1 (2-(2
      (diisopropylphosphino)phenyl)-1-methyl-1H-indole). This catalyst system can be
      applied to a wide range of aryl sulfonates and shows excellent C-3
      regioselectivity of imidazo[1,2-a]pyridine. These results represent the first
      examples of using tosylate- and mesylate-functionalized arenes as the
      electrophile partners for this regioselective direct arylation. 

PMID- 25607731
TI  - Isolation and characterization of six AP2/ERF transcription factor genes in
      Chrysanthemum nankingense.
AB  - The AP2/ERF family of plant transcription factors (TFs) regulate a variety of
      developmental and physiological processes. Here, we report the isolation of six
      AP2/ERF TF family genes from Chrysanthemum nankingense. On the basis of sequence
      similarity, one of these belonged to the Ethylene Responsive Factor (ERF)
      subfamily and the other five to the Dehydration Responsive Element Binding
      protein (DREB) subfamily. A transient expression experiment showed that all six
      AP2/ERF proteins localized to the nucleus. A yeast-one hybrid assay demonstrated
      that CnDREB1-1, 1-2 and 1-3 all function as transactivators, while CnERF1,
      CnDREB3-1 and 3-2 have no transcriptional activation ability. The transcription
      response of the six TFs in response to wounding, salinity and low temperature
      stress and treatment with abscisic acid (ABA), salicylic acid (SA) and jasmonic
      acid (JA) showed that CnERF1 was up-regulated by wounding and low temperature
      stress but suppressed by salinity stress. The transcription of CnDREB1-1, 1-2 and
      1-3 was down-regulated by ABA and JA to varying degrees. CnDREB3-1 and 3-2 was
      moderately increased or decreased by wounding and SA treatment, suppressed by
      salinity stress and JA treatment, and enhanced by low temperature stress and ABA
      treatment. 

PMID- 25607732
TI  - Variation and genetic structure in Platanus mexicana (Platanaceae) along riparian
      altitudinal gradient.
AB  - Platanus mexicana is a dominant arboreal species of riparian ecosystems. These
      ecosystems are associated with altitudinal gradients that can generate genetic
      differences in the species, especially in the extremes of the distribution.
      However, studies on the altitudinal effect on genetic variation to riparian
      species are scarce. In Mexico, the population of P. mexicana along the Colipa
      River (Veracruz State) grows below its reported minimum altitude range, possibly
      the lowest where this tree grows. This suggests that altitude might be an
      important factor in population genetics differentiation. We examined the genetic
      variation and population structuring at four sites with different altitudes (70,
      200, 600 and 1700 m a.s.l.) using ten inter-simple sequence repeats (ISSR)
      markers. The highest value for Shannon index and Nei's gene diversity was
      obtained at 1700 m a.s.l. (He = 0.27, Ne = 1.47, I = 0.42) and polymorphism
      reached the top value at the middle altitude (% p = 88.57). Analysis of molecular
      variance (AMOVA) and STRUCTURE analysis indicated intrapopulation genetic
      differentiation. The arithmetic average (UPGMA) dendrogram identified 70 m a.s.l.
      as the most genetically distant site. The genetic structuring resulted from
      limited gene flow and genetic drift. This is the first report of genetic
      variation in populations of P. mexicana in Mexico. This research highlights its
      importance as a dominant species, and its ecological and evolutionary
      implications in altitudinal gradients of riparian ecosystems. 

PMID- 25607733
TI  - Insecticide-mediated up-regulation of cytochrome P450 genes in the red flour
      beetle (Tribolium castaneum).
AB  - Some cytochrome P450 (CYP) genes are known for their rapid up-regulation in
      response to insecticide exposures in insects. To date, however, limited
      information is available with respect to the relationships among the insecticide
      type, insecticide concentration, exposure duration and the up-regulated CYP
      genes. In this study, we examined the transcriptional response of eight selected
      CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5
      and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium
      castaneum. Reverse transcription quantitative PCR (RT-qPCR) revealed that CYP4G7
      and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06
      fold, respectively), permethrin (2.00- and 2.03-fold) and lambda-cyhalothrin
      (1.73- and 1.81-fold), whereas CYP4BR3 and CYP345A1 can be significantly up
      regulated by imidacloprid (1.99- and 1.83-fold) when 20-day larvae were exposed
      to each of these insecticides at the concentration of LC20 for 24 h. Our studies
      also showed that similar levels of up-regulation can be achieved for CYP4G7,
      CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or
      imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated
      that up-regulation of these CYP genes was rapid and only required low
      concentrations of insecticides, and the up-regulation not only depended on the
      CYP genes but also the type of insecticides. Our results along with those from
      previous studies also indicated that there were no specific patterns for
      predicting the up-regulation of specific CYP gene families based on the
      insecticide classification. 

PMID- 25607734
TI  - Antimicrobial polymers with metal nanoparticles.
AB  - Metals, such as copper and silver, can be extremely toxic to bacteria at
      exceptionally low concentrations. Because of this biocidal activity, metals have
      been widely used as antimicrobial agents in a multitude of applications related
      with agriculture, healthcare, and the industry in general. Unlike other
      antimicrobial agents, metals are stable under conditions currently found in the
      industry allowing their use as additives. Today these metal based additives are
      found as: particles, ions absorbed/exchanged in different carriers, salts, hybrid
      structures, etc. One recent route to further extend the antimicrobial
      applications of these metals is by their incorporation as nanoparticles into
      polymer matrices. These polymer/metal nanocomposites can be prepared by several
      routes such as in situ synthesis of the nanoparticle within a hydrogel or direct
      addition of the metal nanofiller into a thermoplastic matrix. The objective of
      the present review is to show examples of polymer/metal composites designed to
      have antimicrobial activities, with a special focus on copper and silver metal
      nanoparticles and their mechanisms. 

PMID- 25607735
TI  - Prevention of osteoporosis by oral administration of phytate-removed and
      deamidated soybean beta-conglycinin.
AB  - Phytate-removed and deamidated soybean beta-conglycinin (PrDS) prepared by ion
      exchange resins was supplemented to be 4% in the diet administered to
      ovariectomized rats to investigate its preventive effect on osteoporosis. The
      apparent calcium absorption rate decreased following ovariectomy and was not
      replenished by oral administration of phytate-removed soybean beta-conglycinin
      (PrS) or casein. On the other hand, administration of PrDS restored the calcium
      absorption rate to the same level as the sham group. Markers of bone resorption,
      such as serum parathyroid hormone (PTH) and urinary deoxypyridinoline (DPD),
      increased, and the bone mineral density and breaking stress decreased following
      ovariectomy. However, PrDS supplementation suppressed the changes caused by the
      decrease in calcium absorption from the small intestine. Therefore, PrDS
      supplementation shows promise for the prevention of postmenopausal osteoporosis. 

PMID- 25607737
TI  - Simultaneous multiselective spectroelectrochemical fiber-optic sensor:
      demonstration of the concept using methylene blue and ferrocyanide.
AB  - Herein, we present a novel spectroelectrochemical fiber-optic sensor that
      combines electrochemistry, spectroscopy, and electrostatic adsorption in three
      modes of selectivity. The proposed sensor is simple and consists of a gold mesh
      cover on a multimode fiber optic that uses attenuated total reflection as the
      optical detection mode. The sensing is based on changes in the attenuation of the
      light that passes through the fiber-optic core accompanying the electrochemical
      oxidation-reduction of an analyte at the electrode. Methylene blue and
      ferrocyanide were used as model analytes to evaluate the performance of the
      proposed sensor. The optical transmission changes generated by electrochemical
      manipulation showed a good linear relationship with the concentration and the
      limits of detection (3sigma) for methylene blue and ferrocyanide at 2.0 * 10(-7)
      and 1.6 * 10(-3) M, respectively. The sensor responses were successfully enhanced
      with an additional level of selectivity via an electrostatically adsorbed, self
      assembled monolayer (SAM), which consisted of a silane coupling layer, a
      polyanion, and a polycation. The improvement observed in the sensitivity of a SAM
      modified fiber-optic sensor was rather encouraging. The optimized sensor had
      detection limits (3sigma) of 8.3 * 10(-9) M for methylene blue and 7.1 * 10(-4) M
      for ferrocyanide. The developed sensor was successfully applied to the detection
      of ferrocyanide in simulated nuclear waste. 

PMID- 25607736
TI  - Running exercise alleviates pain and promotes cell proliferation in a rat model
      of intervertebral disc degeneration.
AB  - Chronic low back pain accompanied by intervertebral disk degeneration is a common
      musculoskeletal disorder. Physical exercise, which is clinically recommended by
      international guidelines, has proven to be effective for degenerative disc
      disease (DDD) patients. However, the mechanism underlying the analgesic effects
      of physical exercise on DDD remains largely unclear. The results of the present
      study showed that mechanical withdrawal thresholds of bilateral hindpaw were
      significantly decreased beginning on day three after intradiscal complete
      Freund's adjuvant (CFA) injection and daily running exercise remarkably reduced
      allodynia in the CFA exercise group beginning at day 28 compared to the
      spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the
      exercise group returned nearly to baseline at the end of experiment, but severe
      pain persisted in the control group. Histological examinations performed on day
      70 revealed that running exercise restored the degenerative discs and increased
      the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP).
      Furthermore, immunofluorescence labeling revealed significantly higher numbers of
      5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28,
      42, 56 and 70, which indicated more rapid proliferation compared to the control
      at the corresponding time points. Taken together, these results suggest that
      running exercise might alleviate the mechanical allodynia induced by intradiscal
      CFA injection via disc repair and cell proliferation, which provides new evidence
      for future clinical use. 

PMID- 25607738
TI  - A few key points about figure presentation.

PMID- 25607739
TI  - A multicentered prospective analysis of diagnosis, risk factors, and outcomes
      associated with pediatric ventilator-associated pneumonia.
AB  - OBJECTIVE: To assess risk factors and outcomes associated with pediatric
      ventilator-associated pneumonia. DESIGN: Multicentered prospective observational
      cohort. SETTING: Children's hospitals in the United States. PATIENTS:
      Mechanically ventilated patients less than 18 years old. MEASUREMENTS AND MAIN
      RESULTS: Prospective evaluation of the prevalence, risk factors, and outcomes of
      pediatric ventilator-associated pneumonia along with evaluation of diagnostic
      criterion for pediatric ventilator-associated pneumonia. The prevalence of
      pediatric ventilator-associated pneumonia was 5.2% (n = 2,082), for a rate of
      7.1/1,000 ventilator days. Patients with ventilator-associated pneumonia had a
      longer unadjusted ICU length of stay (p < 0.0001) and increased length of
      mechanical ventilation by more than 11 days (p < 0.0001). After adjustment for
      patient factors, ICU length of stay (p = 0.03) and mechanical ventilation days (p
      = 0.001) remained significant. Patients with ventilator-associated pneumonia were
      almost three times more likely to die (p = 0.007). Independent risk factors for
      ventilator-associated pneumonia were reintubation and part-time ventilation.
      CONCLUSIONS: Pediatric ventilator-associated pneumonia is common in mechanically
      ventilated pediatric patients. These patients have longer length of stay, longer
      duration of mechanical ventilation, and increased risk for mortality.

PMID- 25607741
TI  - Implementation of a pediatric critical care focused bedside ultrasound training
      program in a large academic PICU.
AB  - OBJECTIVES: To determine the feasibility and describe the process of implementing
      a pediatric critical care bedside ultrasound program in a large academic PICU and
      to evaluate the impact of bedside ultrasound on clinical management. DESIGN:
      Retrospective case series, description of program implementation. SETTING: Single
      center quaternary noncardiac PICU in a children's hospital. PATIENTS: Consecutive
      patients from January 22, 2012, to July 22, 2012, with bedside ultrasounds
      performed and interpreted by pediatric critical care practitioners.
      INTERVENTIONS: A pediatric critical care bedside ultrasound program consisting of
      a 2-day immersive course followed by clinical performance with internal quality
      assurance review was implemented. Studies performed in the PICU following
      training were documented and reviewed against reference standards including
      subspecialist-performed ultrasound or clinical response. MEASUREMENTS AND MAIN
      RESULTS: Seventeen critical care faculties and eight fellows recorded 201 bedside
      ultrasound studies over 6 months in defined core applications: 57 procedural
      (28%), 76 hemodynamic (38%), 35 thoracic (17%), and 33 abdominal (16%). A quality
      assurance review identified 23 studies (16% of all nonprocedural studies) as
      critical (affected clinical management or gave valuable information). Forty-eight
      percent of those studies (11/23) were within the hemodynamic core. The proportion
      of critical studies were not significantly different across the applications
      (hemodynamic, 11/76 [15%] vs thoracic and abdominal, 12/68 [18%]; p = 0.65).
      Examples of critical studies include evidence of tamponade secondary to pleural
      effusions, identification of pulmonary hypertension, hemodynamic assessment
      before tracheal intubation, recognition of hypovolemia and systemic vascular
      resistance abnormalities, determination of pneumothorax, location of chest tube
      and urinary catheter, and differentiation of pleural fluid from pulmonary
      consolidation. CONCLUSIONS: Implementation of a critical care bedside ultrasound
      program for critical care providers in a large academic PICU is feasible. Bedside
      ultrasound evaluation and interpretation by intensivists affected the management
      of critically ill children.

PMID- 25607740
TI  - Longer RBC storage duration is associated with increased postoperative infections
      in pediatric cardiac surgery.
AB  - OBJECTIVES: Infants and children undergoing open heart surgery routinely require
      multiple RBC transfusions. Children receiving greater numbers of RBC transfusions
      have increased postoperative complications and mortality. Longer RBC storage age
      is also associated with increased morbidity and mortality in critically ill
      children. Whether the association of increased transfusions and worse outcomes
      can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for
      congenital heart disease is unknown. INTERVENTIONS: One hundred and twenty-eight
      consecutively transfused children undergoing repair or palliation of congenital
      heart disease with cardiopulmonary bypass who were participating in a randomized
      trial of washed versus standard RBC transfusions were evaluated for an
      association of RBC storage age and clinical outcomes. To avoid confounding with
      dose of transfusions and timing of infection versus timing of transfusion, a
      subgroup analysis of patients only transfused 1-2 units on the day of surgery was
      performed. MEASUREMENTS AND MAIN RESULTS: Mortality was low (4.9%) with no
      association between RBC storage duration and survival. The postoperative
      infection rate was significantly higher in children receiving the oldest blood
      (25-38 d) compared with those receiving the freshest RBCs (7-15 d) (34% vs 7%; p
      = 0.004). Subgroup analysis of subjects receiving only 1-2 RBC transfusions on
      the day of surgery (n = 74) also demonstrates a greater prevalence of infections
      in subjects receiving the oldest RBC units (0/33 [0%] with 7- to 15-day storage;
      1/21 [5%] with 16- to 24-day storage; and 4/20 [20%] with 25- to 38-day storage;
      p = 0.01). In multivariate analysis, RBC storage age and corticosteroid
      administration were the only predictors of postoperative infection. Washing the
      oldest RBCs (> 27 d) was associated with a higher infection rate and increased
      morbidity compared with unwashed RBCs. DISCUSSION: Longer RBC storage duration
      was associated with increased postoperative nosocomial infections. This
      association may be secondary in part, to the large doses of stored RBCs
      transfused, from single-donor units. Washing the oldest RBCs was associated with
      increased morbidity, possibly from increased destruction of older, more fragile
      erythrocytes incurred by washing procedures. Additional studies examining the
      effect of RBC storage age on postoperative infection rate in pediatric cardiac
      surgery are warranted.

PMID- 25607742
TI  - A training program for anthropometric measurements by a dedicated nutrition
      support team improves nutritional status assessment of the critically ill child.
AB  - OBJECTIVES: The cornerstone of an optimal nutrition approach in PICUs is to
      evaluate the nutritional status of any patient. Anthropometric measurements and
      nutritional indices calculation allow for nutritional status assessment, which is
      not often part of routine management, as it is considered difficult to perform in
      this setting. We designed a study to evaluate the impact of a training program by
      the PICU nutritional support team on the implementation of routine anthropometric
      measurements on our PICU. DESIGN: A prospective study was performed over a 2-year
      period, which included: a baseline evaluation of nutritional assessment,
      knowledge, anthropometric measurements (weight, height, and head and mid upper
      arm circumferences), and nutritional indices calculation in patient files. This
      was followed by a training program to implement the newly developed nutrition
      assessment guidelines, which included anthropometrical measurements and also the
      interpretation of these. The impact of this nutritional assessment program was
      reviewed annually for 2 years after the implementation. SETTING: PICU--Lyon,
      France. PATIENTS AND SUBJECTS: PICU nursing and medical staff, and patients
      admitted in February 2011, 2012, and 2013. INTERVENTIONS: Training program.
      MEASUREMENTS AND MAIN RESULTS: Ninety-nine percent of staff (n = 145) attended
      the individual teaching. We found significant progress in nutritional awareness
      and confidence about nutritional assessment following the teaching program. In
      addition, an improvement in staff knowledge about undernutrition and its
      consequences were found. We enrolled 41, 55, and 91 patients in 2011, 2012, and
      2013, respectively. There was a significant increase in anthropometric
      measurements during this time: 32%, 65% (p = 0.002), and 96% in 2013 (p < 0.001).
      Nutritional indices were calculated in 20%, 74% (p < 0.001), and 96% (p < 0.001)
      of cases. CONCLUSIONS: This is the first study, showing that a targeted
      nutritional assessment teaching program that highlights both the importance and
      techniques of anthropometrical measurements has successfully been implemented in
      a PICU. It managed to improve staff knowledge and nutritional practice.

PMID- 25607743
TI  - Appropriateness of disposition following telemedicine consultations in rural
      emergency departments.
AB  - OBJECTIVES: To compare the appropriateness of hospital admission in eight rural
      emergency departments among a cohort of acutely ill and injured children who
      receive telemedicine consultations from pediatric critical care physicians to a
      cohort of similar children who receive telephone consultations from the same
      group of physicians. DESIGN: Retrospective cohort study between January 2003 and
      May 2012. SETTING: Eight rural emergency departments in Northern California.
      PATIENTS: Acutely ill and injured children triaged to the highest-level triage
      category who received either telemedicine or telephone consultations.
      INTERVENTIONS: Telemedicine and telephone consultations. MEASUREMENTS AND MAIN
      RESULTS: We compared the overall and stratified observed-to-expected hospital
      admission ratios between telemedicine and telephone cohorts by calculating the
      risk of admission using the second generation of Pediatric Risk of Admission
      score and the Revised Pediatric Emergency Assessment Tool. A total of 138 charts
      were reviewed; 74 children received telemedicine consultations and 64 received
      telephone consultations. The telemedicine cohort had fewer hospital admissions
      compared with the telephone cohort (59.5% vs 87.5%; p < 0.05). Although the
      telemedicine cohort had lower observed-to-expected admission ratios than the
      telephone cohort, these differences were not statistically different (Pediatric
      Risk of Admission II, 2.36 vs 2.58; Revised Pediatric Emergency Assessment Tool,
      2.34 vs 2.57). This result did not change when the cohorts were stratified into
      low (below median) and high (above median) risk of admission cohorts, using
      either Pediatric Risk of Admission II (low risk, 18.25 vs 22.81; high risk, 1.40
      vs 1.54) or Revised Pediatric Emergency Assessment Tool (low risk, 5.35 vs 5.94;
      high risk, 1.51 vs 1.81). CONCLUSIONS: Although the overall admission rate among
      patients receiving telemedicine consultations was lower than that among patients
      receiving telephone consultations, there were no statistically significant
      differences between the observed-to-expected admission ratios using Pediatric
      Risk of Admission II and Revised Pediatric Emergency Assessment Tool. Our
      findings may be reassuring in the context of previous research, suggesting that
      telemedicine specialty consultations can aid in the delivery of more appropriate,
      safer, and higher quality of care.

PMID- 25607744
TI  - Standardizing postoperative PICU handovers improves handover metrics and patient
      outcomes.
AB  - OBJECTIVES: To improve handover communication and patient outcomes for
      postoperative admissions to a multidisciplinary PICU. DESIGN: Prospective cohort
      study. SETTING: Multidisciplinary PICU in a university hospital. SUBJECTS: The
      multidisciplinary team responsible for postoperative PICU admissions and patient
      care, including attending, fellow, house staff physicians, and nurses from
      pediatric critical care medicine, surgery, and anesthesia. INTERVENTIONS: An
      online survey distributed to PICU, surgery, and anesthesia providers identified
      existing barriers and challenges to effective postoperative PICU handovers and
      guided the formation of a standard protocol. Handovers for postoperative PICU
      admissions were then directly observed for 3 months pre- and postimplementation
      of the protocol, with data collected on communication, metrics, and patient
      outcomes. Observations and data collection, as well as the online provider
      survey, were repeated approximately 1 year after handover protocol
      implementation. MEASUREMENTS AND MAIN RESULTS: Survey data demonstrated increases
      in provider ratings of handover attendance, communication, and quality after
      implementation of the handover protocol (p < 0.001). Surgical report errors were
      eliminated (p = 0.03), and the prevalence of provider attendance for the handover
      duration increased from 39.3% to 68.2% (p = 0.01). Following protocol
      implementation, fewer patients experienced antibiotic delays (34.5% to 13.9%; p =
      0.03) or required hemodynamic or respiratory interventions within the first 6
      hours of PICU admission (24.6% to 9.1%; p = 0.04). Patients received their first
      dose of analgesia (62.3 to 17.4 min; p = 0.01) and had their admission laboratory
      studies sent (42.3 to 32.9 min; p = 0.04) more quickly. Data collected at 12
      months postimplementation demonstrated sustained reductions in analgesia timing,
      antibiotic delays, and handover barriers. CONCLUSIONS: Postoperative
      communication and patient outcomes can be improved and sustained over time with
      implementation of a standardized handover protocol.

PMID- 25607745
TI  - Novel 755-nm diode laser vs. conventional 755-nm scanned alexandrite laser: Side
      by-side comparison pilot study for thorax and axillary hair removal.
AB  - BACKGROUND: Alexandrite (755 nm) and diode lasers (800-810 nm) are commonly used
      for hair removal. The alexandrite laser technology is somewhat cumbersome whereas
      new diode lasers are more robust. Recently, alexandrite-like 755 nm wavelength
      diodes became available. OBJECTIVES: To compare the efficacy, tolerability, and
      subject satisfaction of a 755 nm diode laser operated in conventional (HR) and
      non-conventional in-motion (SHR) modes with a conventional scanned alexandrite
      755 nm laser for chest and axillary hair removal. MATERIALS AND METHODS: A
      prospective, single-center, proof of principle study was designed to evaluate the
      safety, efficacy and handling of a 755 nm diode laser system in comparison to a
      standard alexandrite 755 nm scanning hair removal laser. RESULTS: The new 755 nm
      diode is suitable to be used in SHR and HR mode and has been tested for its
      safety, efficacy and handling in a volunteer with success. Overall, both systems
      showed a high efficacy in hair reduction (88.8% 755 nm diode laser vs. 77.7% 755
      nm alexandrite laser). Also, during the study period, no severe adverse effects
      were reported. CONCLUSION: The new 755 nm diode laser is as effective and safe as
      the traditional 755 nm alexandrite laser. Additionally, treatment with the 755 nm
      diode laser with HR and SHR modes was found to be less painful.

PMID- 25607746
TI  - Evaluation of Wound Healing Activity of Ethanolic Extract of Pongamia pinnata
      Bark.
AB  - Present study evaluate wound healing activity of ethanolic extract of stem bark
      of Pongamia pinnata (PP). Evaluation of wound healing activity, 2 wound models
      were used I. e., incision and excision wounds were perform in this study on
      Albino wistar rats (150-200 g). The rats were been treated with 10% and 5%
      ointment base formulation at dose 15 ul/wound topically. The parameters studied
      were breaking strength in case of incision wounds, epithelization period and
      wound area in case of excision wound. The ethanolic extract treated group showed
      a significant (P < 0.01) reduction in the wound breaking strength in incision
      type of wound model and significant increase in epithelization period and
      reduction in percentage of wound area in excision type of wound model as compared
      to control group. Extract treated groups showed significant (P < 0.01)
      improvement in all the wound healing parameters of incision and excision wound
      models as compared to control. This study justify the traditional use of
      ethanolic extract of Pongamia pinnata stem bark shows wound healing property.

PMID- 25607747
TI  - Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-beta
      Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles.
AB  - The aim of the present work was to encapsulate 18-beta-Glycyrrhetinic acid (GLA)
      in albumin conjugated poly(lactide-co-glycolide) (PLGA) nanoparticles by a
      modified nanoprecipitation method. Nanoparticles (NPs) were prepared by different
      drug to polymer ratios, human serum albumin (HSA) content, dithiothreitol (as
      producer of free thiol groups) content, and acetone (as non-solvent in
      nanoprecipitation). NPs with a size ranging from 126 to 174 nm were achieved. The
      highest entrapment efficiency (89.4+/-4.2%) was achieved when the ratio of drug
      to polymer was 1:4. The zeta potential of NPs was fairly negative (-8 to -12).
      Fourier transform infrared spectroscopy and differential scanning calorimetry
      proved the conjugation of HSA to PLGA NPs. In vitro release profile of NPs showed
      2 phases: an initial burst for 4 h (34-49%) followed by a slow release pattern up
      to the end. The antibacterial effects of NPs against Staphylococcus aureus,
      Staphylococcus epidermidis and Pseudomonas aeruginosa were studied by
      microdilution method. The GLA-loaded NPs showed more antibacterial effect than
      pure GLA (2-4 times). The anticancer MTT test revealed that GLA-loaded NPs were
      approximately 9 times more effective than pure GLA in Hep G2 cells. 

PMID- 25607748
TI  - Development of QSAR for antimicrobial activity of substituted benzimidazoles.
AB  - QSAR analysis has been done to correlate antimicrobial activity of substituted
      benzimidazole derivatives with their physicochemical parameters. Developed QSAR
      models have been cross validated using leave one out (LOO) method. Statistical
      parameters like probable error of the coefficient of correlation (PE), least
      square error (LSE), Friedman's lack of fit measure (LOF), standard error of
      prediction (SEP) and quality value (Q) were also used to cross validate the
      models. QSAR studies established the importance of WAP, Mlog P and UI in
      describing the antimicrobial activities of substituted benzimidazole derivatives.

PMID- 25607749
TI  - Performance of antioxidative compounds under frying conditions: A review.
AB  - Although much study has been done assessing activity of antioxidants at ambient
      and accelerated storage temperatures, the results cannot correctly depict their
      performance under frying conditions. Due to the stringent conditions imposed,
      most conventional antioxidative compounds failed under frying conditions,
      suggesting the need for a continuous modification to improve their effectiveness.
      Although syntheses and performance evaluation of over a hundred (semi)synthetic
      antioxidants have been reported in literature, only a small fraction have been
      specifically designed and/or evaluated under frying conditions. Here, the
      performance under frying conditions of major natural and synthetic antioxidants
      is reviewed. The recent trend in the designing of antioxidants for frying
      applications is also reviewed with the view of stimulating further study in this
      direction.

PMID- 25607750
TI  - On the photophysics of butadiyne bridged pyrene-phenyl molecular conjugates:
      multiple emissive pathways through locally excited, intramolecular charge
      transfer and excimer states.
AB  - The present work describes the photophysical properties of a group of butadiyne
      bridged pyrene-phenyl molecular hybrids having different substitutions with
      varying donor and acceptor abilities. In addition to emission from the locally
      excited (LE) state originating from the pyrene moiety, intramolecular charge
      transfer (ICT) emissions were observed in molecules with donor-acceptor
      character. The positions of the ICT emission maxima varied over a wide range of
      wavelengths (475-600 nm). Pyrene behaved as a donor when a strong acceptor group
      (-CN) was attached to the phenyl ring and it behaved as an acceptor when the
      phenyl group contained a strong donor group (-NMe2). In mixed aqueous solvents at
      higher percentages of water (80-99%), the derivatives showed emissions from the
      aggregate state in addition to the LE and ICT states. Emissions from the
      aggregate states of the derivatives were centred in the range 510-560 nm. The
      aggregate state emissions were found to originate from static excimers involving
      pyrene moieties. A detailed structure-property relationship of the butadiynyl
      derivatives was revealed in this study. 

PMID- 25607751
TI  - Increasing trends of syphilis among men who have sex with men in high income
      countries.
AB  - Background The epidemiology of syphilis, and therefore the population most
      impacted, differs between countries. Many developed countries have reported an
      increase in syphilis notifications among men who have sex with men (MSM) over the
      past decade. METHODS: The rates of syphilis notifications between 2000 and 2013
      in the 31 countries categorised by the Organisation for Economic Co-operation and
      Development (OECD) as high income were investigated. Data was taken primarily
      from published national surveillance reports, and a male-to-female ratio
      substantially greater than two in syphilis notifications was taken as a proxy for
      the infection being disproportionately diagnosed in MSM. RESULTS: Data was
      available for 27 high-income countries. The male-to-female ratio exceeded two in
      all but four countries. This ratio significantly increased across all
      geographical areas over time. Globally, the male-to-female ratio in these
      countries increased from 4.1 in 2000 to 7.9 in 2013 (P=0.001). Furthermore, the
      proportion of male cases reported as being among MSM increased over time from
      26.8% to 55.0% between 2000 and 2013 (P<0.001). CONCLUSION: These data show that
      in countries with high income, there is a near universal finding of increasing
      rates of syphilis in MSM. It is therefore clear that no country has identified an
      effective method to control syphilis in this population.

PMID- 25607752
TI  - Massive Subcutaneous Masses on the Back Related to beta2-Microglobulin
      Amyloidosis.

PMID- 25607754
TI  - Bamboo-like carbon nanotube/Fe3C nanoparticle hybrids and their highly efficient
      catalysis for oxygen reduction.
AB  - The design of a new class of non-noble-metal catalysts with oxygen reduction
      reaction (ORR) activity superior to that of Pt is extremely important for future
      fuel cell devices. Here we demonstrate a one-pot, large-scale protocol for the
      controlled synthesis of new one-dimensional bamboo-like carbon nanotube/Fe(3)C
      nanoparticle hybrid nanoelectrocatalysts, which are directly prepared by
      annealing a mixture of PEG-PPG-PEG Pluronic P123, melamine, and Fe(NO(3))(3) at
      800  degrees C in N(2). The resulting hybrid electrocatalysts show very high ORR
      activity with a half-wave potential of 0.861 V (vs reversible hydrogen electrode)
      in 0.10 M KOH solution, 49 mV more positive than that of 20 wt% Pt/C catalyst.
      Furthermore, they exhibit good ORR activity in acidic media, with an onset
      potential comparable to that of the Pt/C catalyst. Most importantly, they show
      much higher stability and better methanol tolerance, with almost no ORR
      polarization curve shift and no change of the oxygen reduction peak in the cyclic
      voltammogram in the presence of 1.0 M methanol, than those of the commercial Pt/C
      catalyst in both alkaline and acidic solutions. This makes them one of the best
      non-noble-metal catalysts ever reported for ORR in both alkaline and acidic
      solutions.

PMID- 25607753
TI  - Hsp90 inhibitor NVP-AUY922 enhances the radiation sensitivity of lung cancer cell
      lines with acquired resistance to EGFR-tyrosine kinase inhibitors.
AB  - Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase
      inhibitors (TKIs) is a critical issue that needs to be overcome in the treatment
      of patients with non-small cell lung cancer (NSCLC) harboring EGFR activating
      mutations. EGFR and AKT are client proteins of the 90-kDa heat shock protein
      (Hsp90). Therefore, it was hypothesized that the use of Hsp90 inhibitors might
      allow the resistance to EGFR-TKIs to be overcome. Furthermore, Hsp90 inhibitors
      are known to function as radiosensitizers in various types of cancer. In the
      present study, we evaluated the radiosensitizing effect of the novel Hsp90
      inhibitor, NVP-AUY922 (AUY), on NSCLC cell lines harboring EGFR activating
      mutations and showing acquired resistance to EGFR-TKIs via any of several
      mechanisms. We used HCC827 and PC-9, which are NSCLC cell lines harboring EGFR
      exon 19 deletions, and gefitinib-resistant sublines derived from the same cell
      lines with T790M mutation, MET amplification or stem-cell like properties. AUY
      was more effective against the gefitinib-resistant sublines with T790M mutation
      and MET amplification than against the parental cell lines, although the subline
      with stem cell-like properties showed more than a 10-fold higher resistance to
      AUY than the parental cell line. AUY exerted a significant radiosensitizing
      effect on the parental cell line and the MET-amplified subline through inducing
      G2/M arrest and inhibition of non-homologous end joining (NHEJ). In contrast, the
      radiosensitizing effect of AUY was limited on the subline with stem cell-like
      properties, in which it did not induce G2/M arrest or inhibition of NHEJ. In
      conclusion, combined inhibition of Hsp90 plus radiation was effective, and
      therefore a promising treatment alternative for overcoming major EGFR-TKI
      resistance, such as that induced by T790M mutation or MET amplification. However,
      other approaches are required to overcome minor resistance to EGFR-TKIs, such as
      that observed in cells with stem cell-like properties.

PMID- 25607755
TI  - Somatosensory pleasure circuit: from skin to brain and back.
AB  - The skin senses serve a discriminative function, allowing us to manipulate
      objects and detect touch and temperature, and an affective/emotional function,
      manifested as itch or pain when the skin is damaged. Two different classes of
      nerve fibre mediate these dissociable aspects of cutaneous somatosensation: (i)
      myelinated A-beta and A-delta afferents that provide rapid information about the
      location and physical characteristics of skin contact; and (ii) unmyelinated,
      slow-conducting C-fibre afferents that are typically associated with coding the
      emotional properties of pain and itch. However, recent research has identified a
      third class of C-fibre afferents that code for the pleasurable properties of
      touch - c-tactile afferents or CTs. Clinical application of treatments that
      target pleasant, CT-mediated touch (such as massage therapy) could, in the
      future, provide a complementary, non-pharmacological means of treating both the
      physical and psychological aspects of chronic skin conditions such as itch and
      eczema. 

PMID- 25607756
TI  - International Consensus on Standardization of Data Collection for Complications
      Associated With Esophagectomy: Esophagectomy Complications Consensus Group
      (ECCG).
AB  - INTRODUCTION: Perioperative complications influence long- and short-term outcomes
      after esophagectomy. The absence of a standardized system for defining and
      recording complications and quality measures after esophageal resection has meant
      that there is wide variation in evaluating their impact on these outcomes.
      METHODS: The Esophageal Complications Consensus Group comprised 21 high-volume
      esophageal surgeons from 14 countries, supported by all the major thoracic and
      upper gastrointestinal professional societies. Delphi surveys and group meetings
      were used to achieve a consensus on standardized methods for defining
      complications and quality measures that could be collected in institutional
      databases and national audits. RESULTS: A standardized list of complications was
      created to provide a template for recording individual complications associated
      with esophagectomy. Where possible, these were linked to preexisting
      international definitions. A Delphi survey facilitated production of specific
      definitions for anastomotic leak, conduit necrosis, chyle leak, and recurrent
      nerve palsy. An additional Delphi survey documented consensus regarding critical
      quality parameters recommended for routine inclusion in databases. These quality
      parameters were documentation on mortality, comorbidities, completeness of data
      collection, blood transfusion, grading of complication severity, changes in level
      of care, discharge location, and readmission rates. CONCLUSIONS: The proposed
      system for defining and recording perioperative complications associated with
      esophagectomy provides an infrastructure to standardize international data
      collection and facilitate future comparative studies and quality improvement
      projects.

PMID- 25607757
TI  - The Impact of Nonelective Abdominal Surgery on the Residential Status of Older
      Adult Patients.
AB  - OBJECTIVE: To describe the change in residential status at discharge and 6 months
      after hospitalization among older adults who have undergone nonelective abdominal
      surgery and to identify risk factors associated with discharge to institution.
      BACKGROUND: Surgery in older adults may lead to a loss of independence that
      prevents them from returning to their preadmission residential status.
      Understanding the impact of surgery on residential status and risk factors for
      institutionalization is important for patient counseling, discharge planning, and
      resource allocation. METHODS: Community-dwelling patients aged 70 years and older
      who underwent nonelective abdominal surgery over a 15-month period were
      prospectively enrolled. Residential status before admission, at discharge, and 6
      months after admission was assessed. Multiple logistic regression was used to
      identify factors associated with discharge to institution. RESULTS: Of the 197
      patients who underwent surgery and survived to discharge, 30% were living alone
      before admission and 70% were living with others. At discharge, 72% of patients
      returned to their preadmission residential status and 22% were institutionalized.
      Six months after hospitalization, 55% of institutionalized patients had returned
      to community-living, and 79% of all patients had returned to their preadmission
      residential status. Change in residential status was associated with decreased
      quality of life. Increasing American Society of Anesthesiologists score, frailty,
      surgery for malignancy, and postoperative complications were associated with
      discharge to institution. CONCLUSIONS: The majority of older patients, including
      those who were discharged to an institution, returned to their preadmission
      residential status 6 months after nonelective abdominal surgery.

PMID- 25607758
TI  - Understanding failure to rescue and improving safety culture.

PMID- 25607759
TI  - How to Select Patients With Acute Appendicitis for Appendectomy in Ambulatory
      Surgery?

PMID- 25607760
TI  - Factors Associated With Recurrence and Survival in Lymph Node-negative Gastric
      Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative.
AB  - OBJECTIVES: To determine pathologic features associated with recurrence and
      survival in patients with lymph node-negative gastric adenocarcinoma. STUDY
      DESIGN: Multi-institutional retrospective analysis. BACKGROUND: Lymph node status
      is among the most important predictors of recurrence after gastrectomy for
      gastric adenocarcinoma. Pathologic features predictive of recurrence in patients
      with node-negative disease are less well established. METHODS: Patients who
      underwent curative resection for gastric adenocarcinoma between 2000 and 2012
      from 7 institutions of the US Gastric Cancer Collaborative were analyzed,
      excluding 30-day mortalities and stage IV disease. Competing risks regression and
      multivariate Cox regression were used to determine pathologic features associated
      with time to recurrence and overall survival. Differences in cumulative incidence
      of recurrence were assessed using the Gray method (for univariate nonparametric
      analyses) and the Fine and Gray method (for multivariate analyses) and shown as
      subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively.
      RESULTS: Of 805 patients who met inclusion criteria, 317 (39%) had node-negative
      disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients,
      respectively, experienced recurrence. On multivariate competing risks regression,
      only T-stage 3 or higher was associated with shorter time to recurrence [aSHR =
      2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T
      stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular
      invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95%
      CI, 1.2-3.6) to be associated with decreased overall survival. CONCLUSIONS:
      Despite absence of lymph node involvement, patients with T-stage 3 or higher have
      a significantly shorter time to recurrence. These patients may benefit from more
      aggressive adjuvant therapy and postoperative surveillance regimens.

PMID- 25607761
TI  - Oral Antibiotic Bowel Preparation Significantly Reduces Surgical Site Infection
      Rates and Readmission Rates in Elective Colorectal Surgery.
AB  - OBJECTIVE: To determine the relationship between oral antibiotic bowel
      preparation (OABP) and surgical site infection (SSI) rates in a national
      colectomy cohort. BACKGROUND: OABP for elective colorectal surgery has fallen out
      of favor. Large cohort studies show that OABP is associated with a 50% reduction
      in SSI after colectomy. METHODS: A retrospective analysis of the National
      Surgical Quality Improvement Program colectomy cohort from 2011 to 2012 was
      performed to examine the association between use of OABP and outcomes of SSI,
      length of stay (LOS), and readmission after elective colectomy. Univariate and
      multivariable analyses for SSI were performed. RESULTS: The cohort included 8415
      colorectal operations of which 5291 (62.9%) had a minimally invasive surgical
      (MIS) approach. Overall, 25.6% had no bowel preparation, 44.9% had mechanical
      bowel preparation (MBP) only, and 29.5% received OABP. The SSI rate was 11.1%,
      and it varied by preparation type: 14.9% no preparation, 12.0% MBP, and 6.5% OABP
      (P < 0.001). OABP group had significantly shorter hospital LOS: (median = 4,
      interquartile range: 3-6) versus other preparations (median LOS = 5) (P < 0.001).
      Readmission rates were lowest in OABP (8.1%) and highest in the no preparation
      group (11.8%). Multivariable logistic regressions found OABP associated with
      lower SSI [adjusted odds ratio (ORadj) = 0.46, 95% confidence interval (CI): 0.36
      0.59]. Stratified models found OABP protective for SSI for both open procedures
      (ORadj = 0.40, 95% CI: 0.30-0.53) and MIS procedures (ORadj = 0.48, 95% CI: 0.36
      0.65). CONCLUSIONS: OABP is associated with reduced SSI rates, shorter LOS, and
      fewer readmissions. Adoption of OABP before elective colectomy would reduce SSI
      without effecting LOS. The practice of MBP alone should be abandoned.

PMID- 25607762
TI  - Re: Li J, Ji Z, Li Y. The Comparison of Self-gripping Mesh and Sutured Mesh in
      Open Inguinal Hernia Repair. The Results of Meta-analysis. Ann Surg.
      2014;259:1080--1085.

PMID- 25607763
TI  - Reply to Letter: "Surgical Simulation: Seeing the Bigger Picture and Asking the
      Right Questions".

PMID- 25607764
TI  - Henry Hollingsworth Smith and His Bibliographical Index and Historical Record:
      The Beginning of American Surgical Historiography.
AB  - OBJECTIVE: To explore the details of Henry Hollingsworth Smith's (1815-1890)
      achievement as the first physician to organize in a systematic and chronologic
      manner the details of the history of surgery in America and prepare a register of
      men who performed surgical operations. BACKGROUND: The life of Smith, the
      earliest of the nation's surgeons to elucidate the history of American surgery,
      is little known. His boosting the image of the scalpel wielder helped shape the
      future of the craft, in particular, surgery's rise as a specialty and profession.
      METHODS: An analysis of the published medical literature and unpublished
      documents relating to Smith and his work to document the history of American
      surgery. RESULTS: During the 1850 s, a time when surgery was not considered a
      separate branch of medicine but a mere technical mode of treatment, Smith's
      efforts in surgical history provided much needed encouragement to surgeons in
      their pursuit of professional recognition. CONCLUSIONS: Although Smith's
      accomplishment as the nation's first compiler of the history of American surgery
      has long been forgotten, his effort afforded the men who performed surgical
      operations their earliest measure of self-respect. As such, Smith belongs in
      America's pantheon of surgical heroes.

PMID- 25607765
TI  - Timeout for checklists?

PMID- 25607766
TI  - The Impact of Gastric Bypass on Gastroesophageal Reflux Disease in Morbidly Obese
      Patients.
AB  - OBJECTIVE: To assess the impact of Roux-en-Y gastric bypass (GBP) on
      gastroesophageal reflux disease (GERD) in morbidly obese patients. BACKGROUND:
      Recently, authors have reported that early results of GBP can control GERD.
      However, longer follow-ups based on objective parameters for GERD are missing.
      METHODS: Fifty-three patients [15 men (28%), 39 years old (range, 18-59), body
      mass index = 46 +/- 7.7 kg/m2] were consecutively evaluated for GERD
      irrespectively of related symptoms, before the operation (E1) and at 6 (E2) and
      39 +/- 7 months postoperatively (E3). The end points were (1) esophageal
      syndromes based on the Montreal Consensus and (2) an esophageal acid exposure
      assessment. RESULTS: Body mass index dropped from 46 +/- 7.7 kg/m2 at E1 to 30 +/
      5.2 kg/m2 at E3. Typical reflux syndrome displayed a significant decrease from
      31 (58%) at E1 to 8 (15%) at E2 and 5 (9%) at E3. Statistically significant
      differences occurred between E1 and both postoperative evaluations (P < 0.001).
      Reflux esophagitis was detected in 24 (45%), 17 (32%), and 10 patients (19%) at
      E1, E2, and E3, respectively (P = 0.002). The incidence of GERD decreased in 34
      (64%) and 21 (40%) patients at E1 and E2, respectively, and then in 12 (23%)
      patients at E3. DeMeester scores reduced from 28.6 (E1) to 9.4 (E2) and 1.2 (E3)
      (P < 0.001). CONCLUSIONS: For most morbidly obese patients, in addition to
      causing significant weight loss, GBP reduces GERD symptoms, improves reflux
      esophagitis, and decreases esophageal acid exposure for longer than 3 years.

PMID- 25607767
TI  - Circulating Tumor Cells as a Biomarker for Preoperative Prognostic Staging in
      Patients With Esophageal Cancer.
AB  - OBJECTIVE: We evaluated the prognostic significance of circulating tumor cells
      (CTCs) in patients with esophageal cancer (EC). BACKGROUND: Despite the
      availability of several preoperative diagnostic techniques, accurate pretreatment
      staging of EC remains challenging. METHODS: In this single-center, prospective
      study, peripheral blood samples for CTC analyses were obtained preoperatively
      from 100 patients who were judged to have resectable EC. CTC detection was
      performed using the CellSearch System. Data were correlated with
      clinicopathological parameters and patient outcomes. RESULTS: CTCs were detected
      in 18% (18/100) of all eligible patients. Patients with CTCs showed significantly
      shorter relapse-free (P < 0.001) and overall survival (P < 0.001) than CTC
      negative patients. Even in patients with lymph node invasion and without distant
      metastases (pN+, M0, N = 45), CTC detection indicated significantly worse relapse
      free (P < 0.001) and overall survival (P = 0.007). Multivariate analyses of
      eligible patients identified CTCs as a strong, independent, prognostic indicator
      of tumor recurrence (hazard ratio, 5.063; 95% confidence interval, 2.233-11.480;
      P < 0.001) and overall survival (hazard ratio, 3.128; 95% confidence interval,
      1.492-6.559; P = 0.003). CONCLUSIONS: This is the first study to report that CTCs
      detected by an automated immunomagnetic detection system are independent,
      prognostic indicators of patients' outcome in EC. Thus, implementation of CTCs
      may improve accuracy of preoperative staging in EC.

PMID- 25607769
TI  - Laparoscopy Decreases Pulmonary Complications in Patients Undergoing Major Liver
      Resection: A Propensity Score Analysis.
AB  - OBJECTIVE: To compare both incidence and types of postoperative pulmonary
      complications (PPCs) between laparoscopic major hepatectomy (LMH) and open major
      hepatectomy (OMH). BACKGROUND: LMHs are increasingly performed. Yet, the benefits
      of laparoscopy over laparotomy regarding PPCs remain unknown. METHODS: In this
      multi-institutional study, all patients undergoing OMH or LMH between 1998 and
      2013 were retrospectively reviewed. Risk factors for PPCs were analyzed on
      multivariate analysis. Comparison of both overall rate and types of PPCs between
      OMH and LMH patients was performed after propensity score adjustment on factors
      influencing the choice of the approach. RESULTS: LMH was performed in 226 (18.6%)
      of the 1214 included patients. PPCs occurred in 480 (39.5%) patients including
      symptomatic pleural effusion in 366 (30.1%) patients, respiratory insufficiency
      in 141 (11.6%), acute respiratory distress syndrome in 84 (6.9%), pulmonary
      infection in 80 (6.5%), and pulmonary embolism in 47 (3.8%) patients. On
      multivariate analysis, preoperative hypoprotidemia [hazard ratio (HR): 1.341, 95%
      confidence interval (CI): 1.001-1.795; P = 0.049], open approach (HR: 2.481, 95%
      CI: 1.141-6.024; P = 0.024), right-sided hepatectomy (HR: 2.143, 95% CI: 1.544
      2.975; P < 0.001), concomitant extrahepatic procedures (HR: 1.742, 95% CI: 1.103
      2.750; P = 0.017), transfusion (HR: 2.851, 95% CI: 2.067-3.935; P < 0.001), and
      operative time more than 6 hours (HR: 1.510, 95% CI: 1.127-2.022; P = 0.006) were
      independently associated with PPCs. After propensity score matching, the overall
      incidence of PPCs (13.2% vs 40.5%, P < 0.001), symptomatic pleural effusion
      (11.6% vs 26.4%, P = 0.003), pleural effusion requiring drainage (1.7% vs 9.9%, P
      = 0.006), and acute respiratory distress syndrome (1.7% vs 9.9%, P = 0.006) were
      significantly lower in the laparoscopy group than in the open group. CONCLUSIONS:
      Pure laparoscopy allows reducing PPCs in patients requiring major liver
      resection.

PMID- 25607768
TI  - Immediate Implant Reconstruction Is Associated With a Reduced Risk of Lymphedema
      Compared to Mastectomy Alone: A Prospective Cohort Study.
AB  - OBJECTIVE: We sought to determine the risk of lymphedema associated with
      immediate breast reconstruction compared to mastectomy alone. BACKGROUND:
      Immediate breast reconstruction is increasingly performed at the time of
      mastectomy. Few studies have examined whether breast reconstruction impacts
      development of lymphedema. METHODS: A total of 616 patients with breast cancer
      who underwent 891 mastectomies between 2005 and 2013 were prospectively screened
      for lymphedema at our institution, with 22.2 months' median follow-up.
      Mastectomies were categorized as immediate implant, immediate autologous, or no
      reconstruction. Arm measurements were performed preoperatively and during
      postoperative follow-up using a Perometer. Lymphedema was defined as 10% or more
      arm volume increase compared to preoperative. Kaplan-Meier and Cox regression
      analyses were performed to determine lymphedema rates and risk factors. RESULTS:
      Of 891 mastectomies, 65% (580/891) had immediate implant, 11% (101/891) immediate
      autologous, and 24% (210/891) no reconstruction. The two-year cumulative
      incidence of lymphedema was as follows: 4.08% [95% confidence interval (CI): 2.59
      6.41%] implant, 9.89% (95% CI: 4.98-19.1%) autologous, and 26.7% (95% CI: 20.4
      34.4%) no reconstruction. By multivariate analysis, immediate implant [hazards
      ratio (HR): 0.352, P < 0.0001] but not autologous (HR: 0.706, P = 0.2151)
      reconstruction was associated with a significantly reduced risk of lymphedema
      compared to no reconstruction. Axillary lymph node dissection (P < 0.0001),
      higher body mass index (P < 0.0001), and greater number of nodes dissected (P =
      0.0324) were associated with increased lymphedema risk. CONCLUSIONS: This
      prospective study suggests that in patients for whom implant-based reconstruction
      is available, immediate implant reconstruction does not increase the risk of
      lymphedema compared to mastectomy alone.

PMID- 25607770
TI  - Phenanthrene bioaccumulation in the nematode Caenorhabditis elegans.
AB  - The contribution of food to the bioaccumulation of xenobiotics and hence toxicity
      is still an ambiguous issue. It is becoming more and more evident that universal
      statements cannot be made, but that the relative contribution of food-associated
      xenobiotics in bioaccumulation depends on species, substance, and environmental
      conditions. Yet, small-sized benthic or soil animals such as nematodes have
      largely been disregarded so far. Bioaccumulation of the polycyclic aromatic
      hydrocarbon phenanthrene in the absence and presence of bacterial food was
      measured in the nematode Caenorhabditis elegans. Elimination of phenanthrene in
      the nematodes was biphasic, suggesting that there was a slowly exchanging pool
      within the nematodes or that biotransformation of phenanthrene took place. Even
      with food present, dissolved phenanthrene was still the major contributor to
      bioaccumulated compound in nematode tissues, whereas the diet only contributed
      about 9%. Toxicokinetic parameters in the treatment without food were different
      from the ones of the treatment with bacteria, possibly because nematodes depleted
      their lipid reserves during starvation. 

PMID- 25607771
TI  - Enantioselective total synthesis of (+)-methoxystemofoline and (+)
      isomethoxystemofoline.
AB  - The first enantioselective total synthesis of (+)-methoxystemofoline (2) and (+)
      isomethoxystemofoline (3) has been reported. The synthesis employed the halide
      assisted bromotropanonation method that we developed recently to construct the
      core structure, and Overman's strategy for the implementation of the butenolide
      moiety. Through this work, the structure of methoxystemofoline was revised as
      with an E-alkene, and its absolute configuration was established.

PMID- 25607774
TI  - Discrimination of membrane transporter protein types using K-nearest neighbor
      method derived from the similarity distance of total diversity measure.
AB  - Membrane transporters play crucial roles in the fundamental cellular processes of
      living organisms. Computational techniques are very necessary to annotate the
      transporter functions. In this study, a multi-class K nearest neighbor classifier
      based on the increment of diversity (KNN-ID) was developed to discriminate the
      membrane transporter types when the increment of diversity (ID) was introduced as
      one of the novel similarity distances. Comparisons with multiple recently
      published methods showed that the proposed KNN-ID method outperformed the other
      methods, obtaining more than 20% improvement for overall accuracy. The overall
      prediction accuracy reached was 83.1%, when the K was selected as 2. The
      prediction sensitivity achieved 76.7%, 89.1%, 80.1% for channels/pores,
      electrochemical potential-driven transporters, primary active transporters,
      respectively. Discrimination and comparison between any two different classes of
      transporters further demonstrated that the proposed method is a potential
      classifier and will play a complementary role for facilitating the functional
      assignment of transporters. 

PMID- 25607773
TI  - Comparison of the effect of two different doses of recombinant hepatitis B
      vaccine on immunogenicity in healthy adults.
AB  - The aim of this study was to evaluate the one-month immune response to 2
      different doses (10 and 20 MUg) of recombinant hepatitis B vaccine in adults aged
      20-46 y. Subjects who were negative for hepatitis B surface antigen (HBsAg),
      hepatitis B antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) were
      recruited. The participants were divided into 2 groups: group I received 3 doses
      of 10 MUg hepatitis B vaccine at 0, 1 and 3 months, and group II received 3 doses
      of 20 MUg at the same time points. The anti-HBs levels were measured one month
      after the third vaccination. Among 739 subjects, 62 (9.70%) were positive for
      HBsAg, and 317 subjects were eligible. The anti-HBs seroprotection rates (anti
      HBs >= 10 mIU/mL was considered to indicate seroprotection) after the third
      vaccination were 88.05% and 94.06% in group I and group II respectively, and the
      geometric mean titers were 91.69 and 290.23 mIU/mL respectively. The difference
      in the seroprotection rate was not significant (chi(2) = 2.566, P > 0.05), but
      the GMT after the third dose was significantly lower for group I than for group
      II (F = 20.587, P < 0.05). Better responses were observed in young adults,
      especially in group I. In group I, the seroprotection rate and GMT were
      significantly higher in the 20-35 y group than in the 36-46 y group (P < 0.05);
      there was no significant difference compared to group II (P > 0.05). The
      hepatitis B vaccine has good immunological effect; the 20 MUg dose can be used in
      adults aged 20-46 y and the 10 MUg dose can be used in subjects aged 20-35 years,
      and it should be tested on a larger number of subjects before recommending it for
      adult routine vaccination.

PMID- 25607772
TI  - The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions
      with Galpha12/13 and RhoA.
AB  - In the vertebrate central nervous system, myelinating oligodendrocytes are
      postmitotic and derive from proliferative oligodendrocyte precursor cells (OPCs).
      The molecular mechanisms that govern oligodendrocyte development are incompletely
      understood, but recent studies implicate the adhesion class of G protein-coupled
      receptors (aGPCRs) as important regulators of myelination. Here, we use zebrafish
      and mouse models to dissect the function of the aGPCR Gpr56 in oligodendrocyte
      development. We show that gpr56 is expressed during early stages of
      oligodendrocyte development. In addition, we observe a significant reduction of
      mature oligodendrocyte number and myelinated axons in gpr56 zebrafish mutants.
      This reduction results from decreased OPC proliferation, rather than increased
      cell death or altered neural precursor differentiation potential. Finally, we
      show that these functions are mediated by Galpha12/13 proteins and Rho
      activation. Together, our data establish Gpr56 as a regulator of oligodendrocyte
      development. 

PMID- 25607775
TI  - Modulation of photodeprotection by the sunscreen protocol.
AB  - A protocol for the selective photoremoval of alcohol protecting groups modulated
      by the presence of auxiliary light absorbing molecules is presented. Thus, by
      this method, a single light source was used to selectively remove a specific
      protecting group in the presence of another chromophore with a lower molar
      absorption coefficient. The use of a molecular sunscreen, either internal or
      external, was found to be crucial to achieve high selectivities. 

PMID- 25607776
TI  - Discovery of optimal zeolites for challenging separations and chemical
      transformations using predictive materials modeling.
AB  - Zeolites play numerous important roles in modern petroleum refineries and have
      the potential to advance the production of fuels and chemical feedstocks from
      renewable resources. The performance of a zeolite as separation medium and
      catalyst depends on its framework structure. To date, 213 framework types have
      been synthesized and >330,000 thermodynamically accessible zeolite structures
      have been predicted. Hence, identification of optimal zeolites for a given
      application from the large pool of candidate structures is attractive for
      accelerating the pace of materials discovery. Here we identify, through a large
      scale, multi-step computational screening process, promising zeolite structures
      for two energy-related applications: the purification of ethanol from
      fermentation broths and the hydroisomerization of alkanes with 18-30 carbon atoms
      encountered in petroleum refining. These results demonstrate that predictive
      modelling and data-driven science can now be applied to solve some of the most
      challenging separation problems involving highly non-ideal mixtures and highly
      articulated compounds. 

PMID- 25607777
TI  - Serum beta-crosslaps as predictor of long-term parathyroid hormone levels in
      hemodialysis patients.
AB  - BACKGROUND AND AIMS: Parathyroid hormone (PTH) measurements in hemodialysis (HD)
      patients are routinely performed every 3 to 6 months of therapy, which are
      adjusted in accordance with PTH. However, recent evidences show very high PTH
      biological variability. The aim of our study was to evaluate the role of serum
      beta-crosslap (CTX), a validated marker of bone resorption, as indicator of PTH
      maintenance at different time intervals. METHODS: Forty-six HD patients fulfilled
      the inclusion criteria (HD age of more than 21 months and 7 PTH measurements for
      the last 21 months) for this retrospective cohort study and were enrolled. Data
      of the backward quarter PTH values for the last 21 months were collected from
      clinical records, and a single CTX was measured.To evaluate the relationship
      between CTX value and the maintenance of PTH in the short-term and long-term, 7
      time intervals (3, 6, 9, 12, 15, 18, and 21 months) were stated and the mean
      value of PTH was measured within each interval and calculated for every patient.
      RESULTS: We found the following: (1) positive correlation between mean PTH in
      each time interval and beta-crosslaps with a progressive increase of the
      correlation coefficient (highest value for the 12- and 21-month intervals); (2)
      significant differences between tertiles of beta-crosslaps at 6-, 9-, 12-, 15-,
      18-, and 21-month intervals, with a progressively growing value of the test
      coefficient; and (3) after the computation of receiver operating characteristic
      curves, beta-crosslaps showed to significantly estimate threshold PTH values with
      the highest areas under the curves (AUCs; AUC, 0.763; 95% confidence interval,
      0.625-0.901 for <150 pg/mL of PTH; AUC, 0.774; 95% confidence interval, 0.614
      0.934 for >300 pg/mL of PTH) and best value of both sensitivity and specificity
      at the 12-month time interval (82% and 72% for <150 pg/mL of PTH; 78% and 79% for
      >300 pg/mL of PTH). CONCLUSIONS: In HD patients, beta-crosslaps have a potential
      ability to best estimate backward PTH into 12 months of interval.

PMID- 25607778
TI  - Self-assembly and electrostriction of arrays and chains of hopfion particles in
      chiral liquid crystals.
AB  - Some of the most exotic condensed matter phases, such as twist grain boundary and
      blue phases in liquid crystals and Abrikosov phases in superconductors, contain
      arrays of topological defects in their ground state. Comprised of a triangular
      lattice of double-twist tubes of magnetization, the so-called 'A-phase' in chiral
      magnets is an example of a thermodynamically stable phase with topologically
      nontrivial solitonic field configurations referred to as two-dimensional
      skyrmions, or baby-skyrmions. Here we report that three-dimensional skyrmions in
      the form of double-twist tori called 'hopfions', or 'torons' when accompanied by
      additional self-compensating defects, self-assemble into periodic arrays and
      linear chains that exhibit electrostriction. In confined chiral nematic liquid
      crystals, this self-assembly is similar to that of liquid crystal colloids and
      originates from long-range elastic interactions between particle-like skyrmionic
      torus knots of molecular alignment field, which can be tuned from isotropic
      repulsive to weakly or highly anisotropic attractive by low-voltage electric
      fields. 

PMID- 25607779
TI  - Coexistence of Digenic Mutations in Both Thin (TPM1) and Thick (MYH7) Filaments
      of Sarcomeric Genes Leads to Severe Hypertrophic Cardiomyopathy in a South Indian
      FHCM.
AB  - Mutations in sarcomeric genes are the leading cause for cardiomyopathies.
      However, not many genetic studies have been carried out on Indian cardiomyopathy
      patients. We performed sequence analyses of a thin filament sarcomeric gene,
      alpha-tropomyosin (TPM1), in 101 hypertrophic cardiomyopathy (HCM) patients and
      147 dilated cardiomyopathy (DCM) patients against 207 ethnically matched healthy
      controls, revealing 13 single nucleotide polymorphisms (SNPs). Of these, one
      mutant, S215L, was identified in two unrelated HCM cases-patient #1, aged 44, and
      patient #2, aged 65-and was cosegregating with disease in these families as an
      autosomal dominant trait. In contrast, S215L was completely absent in 147 DCM and
      207 controls. Patient #1 showed a more severe disease phenotype, with poor
      prognosis and a family history of sudden cardiac death, than patient #2.
      Therefore, these two patients and the family members positive for S215L were
      further screened for variations in MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, and
      ACTC. Interestingly, two novel thick filaments, D896N (homozygous) and I524K
      (heterozygous) mutations, in the MYH7 gene were identified exclusively in patient
      #1 and his family members. Thus, we strongly suggest that the coexistence of
      these digenic mutations is rare, but leads to severe hypertrophy in a South
      Indian familial hypertrophic cardiomyopathy (FHCM).

PMID- 25607780
TI  - Spectrum of critical illness in undocumented border crossers. The Arizona-Mexico
      border experience.
AB  - RATIONALE: Approximately 150-250 migrants die each year while attempting to cross
      the border from Mexico to the Southwest United States. Many border crossers
      survive the journey, but some develop life-threatening medical complications.
      Such complications have been subject to little formal analysis. OBJECTIVES: We
      sought to determine the causes of critical illness in this population and to
      analyze the hospital course and outcomes of these patients. METHODS: We
      retrospectively identified border crossers admitted to the intensive care units
      (ICUs) of two major teaching hospitals in southern Arizona. We recorded admitting
      diagnoses, severity of illness, length of stay, resource use, discharge
      diagnoses, and mortality. RESULTS: Our investigation identified 55 admissions to
      adult ICUs between January 1, 2010 and December 31, 2012. The median age of
      patients was 27 years. The median hospital length of stay was 7 days, with a
      median ICU length of stay of 3 days. The median temperature on arrival to the
      emergency department was 36.8 degrees C. The most common admission diagnoses
      included trauma (40), rhabdomyolysis (27), acute liver injury (25), dehydration
      (24), acute kidney injury (19), and encephalopathy (17). Thirteen patients
      presented with respiratory failure, six patients with severe sepsis, and two with
      septic shock. A total of 19 patients required ventilator support during their
      hospital stay, and 30 required at least one surgical intervention. One patient
      required renal replacement therapy. The median Acute Physiology and Chronic
      Health Evaluation II score was 6. All but one patient survived to discharge from
      the hospital. CONCLUSIONS: Border crossers are a unique population of young
      individuals exposed to high temperatures and extreme conditions. Our review of
      border crosser admissions showed that most patients demonstrated signs of
      dehydration and leukocytosis, despite a normal median temperature. The median ICU
      stay was short, despite a high number of patients requiring ventilator support
      and surgical intervention. Only one death occurred in this cohort.

PMID- 25607783
TI  - Principles and approaches for optimizing therapy with unique topical vehicles.

PMID- 25607784
TI  - Should hyaluronic acid fillers be diluted?

PMID- 25607785
TI  - Metastatic hepatocellular carcinoma with paraneoplastic itch: effective treatment
      with naltrexone.

PMID- 25607781
TI  - Adaptive immune responses to Candida albicans infection.
AB  - Fungal infections are becoming increasingly prevalent in the human population and
      contribute to morbidity and mortality in healthy and immunocompromised
      individuals respectively. Candida albicans is the most commonly encountered
      fungal pathogen of humans, and is frequently found on the mucosal surfaces of the
      body. Host defense against C. albicans is dependent upon a finely tuned
      implementation of innate and adaptive immune responses, enabling the host to
      neutralise the invading fungus. Central to this protection are the adaptive Th1
      and Th17 cellular responses, which are considered paramount to successful immune
      defense against C. albicans infections, and enable tissue homeostasis to be
      maintained in the presence of colonising fungi. This review will highlight the
      recent advances in our understanding of adaptive immunity to Candida albicans
      infections. 

PMID- 25607786
TI  - Safety observations in 12095 patients with psoriasis enrolled in an international
      registry (PSOLAR): experience with infliximab and other systemic and biologic
      therapies.
AB  - BACKGROUND: Long-term data are essential to assess the safety of biologic agents
      for the treatment of psoriasis. OBJECTIVE: To evaluate the incidence of adverse
      events of interest (AEIs), including all-cause mortality, major adverse
      cardiovascular events (MACE), malignancy (excluding nonmelanoma skin cancer), and
      serious infections (SI), in patients treated for psoriasis in clinical practice
      settings. METHODS: PSOLAR is a large, ongoing, observational study of patients
      receiving, or eligible to receive, biologic or systemic therapy for psoriasis.
      Cumulative incidence rates of AEIs per 100 patient-years (PY) are reported across
      treatment cohorts: (1) infliximab, (2) ustekinumab, (3) other biologics (eg,
      adalimumab and etanercept), and (4) non-biologic agents. Significant predictors
      of each AEI were identified using Cox proportional hazards regression
      methodology. RESULTS: PSOLAR is now fully enrolled at 12095 patients followed for
      31818PY. The cumulative rate was 0.46/100PY for death, 0.36/100PY for MACE,
      0.68/100PY for malignancy, and 1.50/100PY for SI. Increasing age was a
      significant predictor of all AEIs. A history of cardiovascular disease,
      malignancy, and significant infection was associated with a higher risk of
      developing MACE, malignancy, and SI, respectively. Exposure to infliximab (Hazard
      Ratio [HR]=3.101, P<0.001) and exposure to other biologics (HR=1.736, P<0.001)
      were significant predictors of SI. Use of immunomodulators (HR=1.954, P=0.005)
      was a significant predictor of MACE. Compared with non-biologic therapy, the use
      of biologic agents was not a significant predictor of death, MACE, or malignancy.
      CONCLUSIONS: Based on PSOLAR data through 2013, no new safety concerns were
      observed with infliximab for all-cause mortality, MACE, or malignancy; the data
      suggest that infliximab was associated with serious infections.

PMID- 25607787
TI  - Evaluation of a new adipocytolytic solution: adverse effects and their
      relationship with the number of vials injected.
AB  - Adipocytolytic therapies have always raised the interest of aesthetic medicine
      physicians, mainly because of the great potential to achieve spectacular results
      in localized adiposities reduction. In the last few decades, these results have
      been severely compromised due to the improper or reckless injection of these
      products, to the extent of some of them being banned in many countries. Today,
      there is a new adipocytolytic solution that has been approved, is effective, and
      has theoretic and empiric consensus regarding its safety. The aim of this study
      for which 331 therapeutic sessions were retrospectively analyzed is to provide
      evidence of its safety and efficacy.

PMID- 25607788
TI  - Enhancing transungual delivery and spreading of efinaconazole under the nail
      plate through a unique formulation approach.
AB  - Onychomycosis is a very common nail disorder seen in dermatological practice. It
      is difficult to treat successfully for a multitude of reasons, and although
      topical antifungal therapy might be considered ideal for mild to moderate
      onychomycosis, efficacy has been limited by poor nail penetration of active
      ingredient through the nail plate into the nail bed and nail matrix to the site
      of infection. The intrinsic properties of an antifungal and its vehicle
      formulation are both considered important contributors to effective treatment.
      Here we review the formulation approach to efinaconazole topical solution, 10% an
      effective and well-tolerated treatment for onychomycosis. We demonstrate that the
      low surface tension formulation affords better penetration of efinaconazole
      through the nail plate, and also to the site of infection by spreading into the
      space between the nail and nail bed.

PMID- 25607789
TI  - A comparison of super wide field microscopy systems in mohs surgery.
AB  - Microscopic frozen section interpretation is one of the cornerstones of Mohs
      surgery. The recent development of super wide field (SWF) microscopy can improve
      accuracy and efficiency while reading microscope sections, and also decrease the
      physician's musculoskeletal and ocular strain. Super wide field microscopy
      systems increase viewable field area (VA) by combining low magnification
      objectives, eg, 1x or 2x (Figure 1), with eyepieces that have a higher field
      number. This article reviews 3 SWF microscopy systems: Leica DM2000 (Leica
      Microsystems, Wetzlar, Germany), Nikon Eclipse Ni (Nikon Instruments Inc.,
      Melville, NY), and Olympus BX43 (Olympus, Center Valley, PA). The Leica DM2000's
      1.25x objective results in a VA of 314.16 mm2. The Nikon Eclipse Ni's 1x
      objective results in a VA of 490.87 mm2. The Olympus BX43's 1.25x objective
      results in a VA of 352.99 mm2. The maximum VA at the lowest objective for Nikon
      is nearly 40% greater than for the Olympus and over 50% greater than for the
      Leica. The Nikon Eclipse Ni has a significantly higher maximum VA than the other
      2 systems.

PMID- 25607790
TI  - Evaluation of efficacy and tolerance of a nighttime topical antioxidant
      containing resveratrol, baicalin, and vitamin e for treatment of mild to
      moderately photodamaged skin.
AB  - Resveratrol is an effective anti-aging molecule with diverse biologic activity.
      It functions as a dual antioxidant that can neutralize free radicals and increase
      intrinsic antioxidant capacity. Additionally resveratrol increases mitochondrial
      biogenesis and has anti-inflammatory, anti-diabetic, and anti-cancer activity. In
      this paper we will focus on the use of topically applied resveratrol using a
      proprietary blend containing 1% resveratrol, 0.5% baicalin, and 1% vitamin E.
      This stabilized high concentration formulation demonstrates percutaneous
      absorption and alterations in gene expression such as hemoxygenase-1 (HO-1),
      vascular endothelial growth factor (VEGFA), and collagen 3 (COL3A1). Clinical
      assessment showed a statistically significant improvement in fine lines and
      wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation,
      radiance, and skin roughness over baseline in 12 weeks. Ultrasound measurements
      in the periorbital area showed an average improvement of 18.9% in dermal
      thickness suggesting significant dermal remodeling. These studies confirm that
      topical resveratrol, baicalin, and vitamin E are valuable ingredient that can be
      used for skin rejuvenation.

PMID- 25607791
TI  - Dermatofibrosarcoma protuberans: is mohs surgery truly superior? And the success
      of tyrosine kinase inhibitors.
AB  - Dermatofibrosarcoma protuberans is a rare, slow growing tumor. This growth occurs
      most frequently in males from ages 20 to 50. The most common area on which DFSP
      originates is the trunk. DFSP presents clinically as a pink nodule or as a firm,
      flesh-colored to brown, indurated and exophytic plaque. Pathology shows atypical
      spindle cells of fibroblast origin surrounding a core of collagen. The definitive
      treatment of DFSP is surgical excision. Imatinib is a tyrosine kinase inhibitor
      that has been approved for use in DFSP refractory to surgery.

PMID- 25607792
TI  - Safe and efficacious use of a topical retinoid under occlusion for the treatment
      of mycosis fungoides.

PMID- 25607793
TI  - Effect of skin barrier emulsion cream vs a conventional moisturizer on
      transepidermal water loss and corneometry in atopic dermatitis: a pilot study.
AB  - The repair and maintenance of the epidermal barrier is of the utmost importance
      in the treatment of atopic dermatitis (AD). While barrier creams and emollients
      are considered to be a foundation of AD therapy, there is little comparative data
      between various product options. This was a pilot study with a small sample size
      to investigate the use of skin barrier emulsion cream vs a commonly used
      moisturizing lotion to improve the epidermal barrier in subjects with atopic
      dermatitis.

PMID- 25607794
TI  - Integration of thermal imaging with subsurface radiofrequency thermistor heating
      for the purpose of skin tightening and contour improvement: a retrospective
      review of clinical efficacy.
AB  - INTRODUCTION: Radiofrequency has remained a staple procedure for the treatment of
      skin laxity as therapeutic heat thresholds effectively promote collagen
      remodeling. Nevertheless, comprehensive skin tightening involves both dermal and
      hypodermal collagen remodeling. However, transcutaneous radiofrequency is unable
      to deliver consistent and measurable temperatures to the hypodermal layers.
      Herein, we evaluated a newly emerging approach that provides precise and
      controlled subdermal heating is thermistor-controlled subdermal skin tightening
      (ThermiTight) using a percutaneous radiofrequency treatment probe. METHODS: A
      retrospective analysis of 35 patients was completed on patients having undergone
      ThermiTight for submental skin tightening. Treated sites included under-chin and
      under-chin and jowls. The ThermiTight probe temperature was set between 50 to 60 
      degrees C and was maintained using the thermistor integrated electrode. The probe
      was guided at a deliberate pace, treating a surface area of 3.0 cm2 every two
      minutes. The clinical endpoint was an epidermal temperature of 42  degrees C. Two
      blinded reviewers assessed photographs taken at baseline and 30 days post
      procedure. They were randomly presented with a photograph and asked to rate the
      photograph using a 4.0 skin laxity scale. RESULTS: The combined mean change
      comparing baseline and post-procedure skin laxity scores was -0.78, which was
      statistically significant (Table 2; P<0.0001). Each blinded reviewer correctly
      categorized photographs as either being "baseline" or "post-procedure" 89% of the
      time. No adverse events were reported. DISCUSSION: These data demonstrate the
      safety and efficacy of the ThermiTIght procedure for the treatment of skin
      laxity.

PMID- 25607795
TI  - A surprising case of Mycobacterium avium complex skin infection in an
      immunocompetent patient.
AB  - An acute inflammatory nodule of unknown etiology can pose a formidable diagnostic
      challenge. Here, we highlight the importance of including Mycobacterium avium
      intracellulare complex (MAC) and other atypical mycobacterial infections in the
      differential diagnosis of a cutaneous nodule in an immunocompetent individual. We
      also explore the implications of eczema in the development of a mycobacterial
      infectious process. We report a case of MAC skin infection in an immunocompetent
      individual. The patient is a 49-year-old male with a history of dyshidrotic
      eczema presenting with a fluctuant, non-draining nodule on his right forearm for
      2 to 3 weeks, identified by tissue DNA probe to be a cutaneous MAC infection
      without systemic complications, as serologies and chest X-ray were unremarkable.
      MAC should be included in the broader differential diagnosis of deep fungal vs
      atypical mycobacterial skin infections. Nucleic acid-based assays are an
      important tool in making a definitive diagnosis, allowing for utilization of
      appropriate therapy for the specific etiologic pathogen. Given the patient's
      preceding diagnosis of eczema, it is possible that the compromised skin barrier
      and dampened cytotoxic Th1 activity predisposed the patient to this infection,
      typically appreciated in the immunosuppressed, warranting further investigation
      into the relative risk for atypical mycobacterial infections in the setting of
      eczema.

PMID- 25607796
TI  - Cutaneous non-tuberculous mycobacterial infections in the outpatient setting:
      presentation of a case, review of the literature, and therapeutic considerations.
AB  - Mycobacterial infections are not common issues for many dermatologists.
      Recognition and treatment of these infections are frequently delayed by incorrect
      diagnoses. Frequently, the diagnosis of a mycobacterial infection is hampered by
      coinfection with bacteria including Staphylococcus. In some instances, patients
      will have infections with both mycobacteria and Staphylococcus. For some
      patients, as was the case with the patient reported herein, a biopsy is required
      to establish an accurate diagnosis. Physicians need to keep an open mind when
      presented with cutaneous infections and consider mycobacterial infections for
      patients that do not improve with standard antibacterial medications.

PMID- 25607797
TI  - Challenges and advances in rosacea management.

PMID- 25607798
TI  - Update on the management of rosacea: a status report on the current role and new
      horizons with topical azelaic acid.
AB  - Azelaic acid (AzA) 15% gel has been available in the United States for slightly
      over a decade, approved for treatment of the inflammatory lesions (papules and
      pustules) of rosacea. Efficacy and safety have been established in multiple
      studies both as monotherapy and in combination with oral doxycycline. Azelaic
      acid 15% gel has been shown not to induce epidermal permeability barrier
      impairment, and proper skin care reduces the likelihood of neurosensory adverse
      effects of stinging and burning that can affect a subset of patients with
      rosacea. Azelaic acid 15% gel appears to produce a quicker onset of clinical
      effect than metronidazole in some patients when either agent is used in
      combination with subantimicrobial dose doxycycline; however, both topical agents
      are effective when used in this combination approach for papulopustular rosacea
      (PPR). Although more information is needed on the modes of action of AzA in the
      treatment of rosacea, downregulation of the cathelicidin pathway appears to be
      one operative mode of action based on in vitro and in vivo studies, including
      data from patients treated with AzA 15% gel for PPR. Azelaic acid 15% foam is
      currently in the latter stages of development for PPR, with pivotal studies
      demonstrating efficacy and favorable tolerability, including a very low incidence
      of stinging, burning, and itching even without the use of designated skin care
      products.

PMID- 25607800
TI  - Effect of fulvic acid surface coatings on plutonium sorption and desorption
      kinetics on goethite.
AB  - The rates and extent of plutonium (Pu) sorption and desorption onto mineral
      surfaces are important parameters for predicting Pu mobility in subsurface
      environments. The presence of natural organic matter, such as fulvic acid (FA),
      may influence these parameters. We investigated the effects of FA on Pu(IV)
      sorption/desorption onto goethite in two scenarios: when FA was (1) initially
      present in solution or (2) found as organic coatings on the mineral surface. A
      low pH was used to maximize FA coatings on goethite. Experiments were combined
      with kinetic modeling and speciation calculations to interpret variations in Pu
      sorption rates in the presence of FA. Our results indicate that FA can change the
      rates and extent of Pu sorption onto goethite at pH 4. Differences in the
      kinetics of Pu sorption were observed as a function of the concentration and
      initial form of FA. The fraction of desorbed Pu decreased in the presence of FA,
      indicating that organic matter can stabilize sorbed Pu on goethite. These results
      suggest that ternary Pu-FA-mineral complexes could enhance colloid-facilitated Pu
      transport. However, more representative natural conditions need to be
      investigated to quantify the relevance of these findings. 

PMID- 25607799
TI  - Management of impulse control disorders in Parkinson's disease: Controversies and
      future approaches.
AB  - Impulse control disorders in Parkinson's disease are a group of impulsive
      behaviors most often associated with dopaminergic treatment. Presently, there is
      a lack of high quality evidence available to guide their management. This
      manuscript reviews current management strategies, before concentrating on the
      concept of dopamine agonist withdrawal syndrome and its implications for the
      management of impulse control disorders. Further, we focus on controversies,
      including the role of more recently available anti-parkinsonian drugs, and
      potential future approaches involving routes of drug delivery, nonpharmacological
      treatments (such as cognitive behavioral therapy and deep brain stimulation), and
      other as yet experimental strategies.

PMID- 25607801
TI  - Regulation of neuronal morphogenesis and positioning by ubiquitin-specific
      proteases in the cerebellum.
AB  - Ubiquitin signaling mechanisms play fundamental roles in the cell-intrinsic
      control of neuronal morphogenesis and connectivity in the brain. However, whereas
      specific ubiquitin ligases have been implicated in key steps of neural circuit
      assembly, the roles of ubiquitin-specific proteases (USPs) in the establishment
      of neuronal connectivity have remained unexplored. Here, we report a
      comprehensive analysis of USP family members in granule neuron morphogenesis and
      positioning in the rodent cerebellum. We identify a set of 32 USPs that are
      expressed in granule neurons. We also characterize the subcellular localization
      of the 32 USPs in granule neurons using a library of expression plasmids encoding
      GFP-USPs. In RNAi screens of the 32 neuronally expressed USPs, we uncover novel
      functions for USP1, USP4, and USP20 in the morphogenesis of granule neuron
      dendrites and axons and we identify a requirement for USP30 and USP33 in granule
      neuron migration in the rodent cerebellar cortex in vivo. These studies reveal
      that specific USPs with distinct spatial localizations harbor key functions in
      the control of neuronal morphogenesis and positioning in the mammalian
      cerebellum, with important implications for our understanding of the cell
      intrinsic mechanisms that govern neural circuit assembly in the brain. 

PMID- 25607802
TI  - Strategies to avoid wrongly labelled genomes using as example the detected wrong
      taxonomic affiliation for aeromonas genomes in the GenBank database.
AB  - Around 27,000 prokaryote genomes are presently deposited in the Genome database
      of GenBank at the National Center for Biotechnology Information (NCBI) and this
      number is exponentially growing. However, it is not known how many of these
      genomes correspond correctly to their designated taxon. The taxonomic affiliation
      of 44 Aeromonas genomes (only five of these are type strains) deposited at the
      NCBI was determined by a multilocus phylogenetic analysis (MLPA) and by pairwise
      average nucleotide identity (ANI). Discordant results in relation to taxa
      assignation were found for 14 (35.9%) of the 39 non-type strain genomes on the
      basis of both the MLPA and ANI results. Data presented in this study also
      demonstrated that if the genome of the type strain is not available, a genome of
      the same species correctly identified can be used as a reference for ANI
      calculations. Of the three ANI calculating tools compared (ANI calculator,
      EzGenome and JSpecies), EzGenome and JSpecies provided very similar results.
      However, the ANI calculator provided higher intra- and inter-species values than
      the other two tools (differences within the ranges 0.06-0.82% and 0.92-3.38%,
      respectively). Nevertheless each of these tools produced the same species
      classification for the studied Aeromonas genomes. To avoid possible
      misinterpretations with the ANI calculator, particularly when values are at the
      borderline of the 95% cutoff, one of the other calculation tools (EzGenome or
      JSpecies) should be used in combination. It is recommended that once a genome
      sequence is obtained the correct taxonomic affiliation is verified using ANI or a
      MLPA before it is submitted to the NCBI and that researchers should amend the
      existing taxonomic errors present in databases. 

PMID- 25607803
TI  - Activation of corticotropin-releasing factor 1 receptor: insights from molecular
      dynamics simulations.
AB  - G-protein-coupled receptors (GPCRs) constitute the largest family of membrane
      bound proteins involved in translation of extracellular signals into
      intracellular responses. They regulate diverse physiological and
      pathophysiological processes, and hence, they are prime drug targets for
      therapeutic intervention. In spite of the recent advancements in membrane protein
      crystallography, limited information is available on the molecular signatures of
      activation of GPCRs. Although few studies have been reported for class A GPCRs,
      the activation mechanism of class B GPCRs remains unexplored. Corticotropin
      releasing factor 1 receptor (CRF1R), a class B GPCR, is associated with various
      disease conditions including stress, anxiety, and irritable bowel syndrome. Here,
      we report the activation of CRF1R using accelerated molecular dynamics
      simulations of the apo receptor. The breakage of His155(2.50)-Glu209(3.50) and
      Glu209(3.50)-Thr316(6.42) interactions is found to be crucial in transition of
      the receptor to its active conformation. Compared to the inactive crystal
      structure, major structural rearrangements occurred in the intracellular region
      of the transmembrane (TM) domain upon activation: TM3 twisted away from TM2, and
      an opening of the G-protein binding site occurred as a result of the outward
      movements of TM5 and TM6 from the helical bundle. Further, an inward tilt of TM7
      toward the helical core is observed at the extracellular side, in agreement with
      recent findings (Coin et al. Cell 2013, 155, 1258-1269), where it is proposed
      that this movement helps in establishing favorable interactions with peptide
      agonist. Moreover, different allosteric pathways in the inactive and active
      states are identified using the correlations in torsion angle space. The inactive
      state is found to be less dynamic as compared to the putative active state of the
      receptor. Results from the current study could present a model for class B GPCRs
      activation and aid in the design of CRF1R modulators against brain and metabolic
      disorders. 

PMID- 25607804
TI  - One-step thermal-treatment route to fabricate well-dispersed ZnO nanocrystals on
      nitrogen-doped graphene for enhanced electrochemiluminescence and ultrasensitive
      detection of pentachlorophenol.
AB  - Heteroatom doping enables graphene with novel properties and thus may broaden the
      potential of graphene-based materials. In this paper, novel ZnO-nanocrystal
      decorated nitrogen-doped graphene (N-GR) composites were prepared through a one
      step thermal-treatment route using glycine as the nitrogen source. ZnO
      nanocrystals with a size about 8 nm were well-dispersed and tightly anchored on
      the N-GR sheet. Compared with ZnO-nanocrystal-decorated undoped graphene, the
      ZnO/N-GR nanocomposites could not only enhance the electrochemiluminescence (ECL)
      intensity by 4.3-fold but also moved the ECL onset potential positively for ~200
      mV. All these results could be ascribed to the presence of nitrogen in graphene
      which decreased the barrier of ZnO nanocrystals reduction. Furthermore, the ECL
      sensor based on ZnO/N-GR nanocomposites was fabricated for the ultrasensitive
      detection of pentachlorophenol (PCP). This recyclable and eco-friendly sensor has
      excellent performances including wide linear range (0.5 pM to ~61.1 nM), low
      detection limit (0.16 pM, S/N=3), good selectivity, and stability, which is a
      promising sensor for practical application in environment analysis.

PMID- 25607806
TI  - The impact of time perspective latent profiles on college drinking: a
      multidimensional approach.
AB  - BACKGROUND: Zimbardo and Boyd's(1) time perspective, or the temporal framework
      individuals use to process information, has been shown to predict health
      behaviors such as alcohol use. Previous studies supported the predictive validity
      of individual dimensions of time perspective, with some dimensions acting as
      protective factors and others as risk factors. However, some studies produced
      findings contrary to the general body of literature. In addition, time
      perspective is a multidimensional construct, and the combination of perspectives
      may be more predictive than individual dimensions in isolation; consequently,
      multidimensional profiles are a more accurate measure of individual differences
      and more appropriate for predicting health behaviors. OBJECTIVES: The current
      study identified naturally occurring profiles of time perspective and examined
      their association with risky alcohol use. METHODS: Data were collected from a
      college student sample (n = 431, mean age = 20.41 years) using an online survey.
      Time perspective profiles were identified using latent profile analysis. RESULTS:
      Bootstrapped regression models identified a protective class that engaged in
      significantly less overall drinking (beta = -0.254) as well as engaging in
      significantly less episodic high risk drinking (beta = -0.274). There was also
      emerging evidence of a high risk time perspective profile that was linked to more
      overall drinking (beta = 0.198) and engaging in more high risk drinking (beta =
      0.245), though these differences were not significant. CONCLUSIONS/IMPORTANCE:
      These findings support examining time perspective in a multidimensional framework
      rather than individual dimensions in isolation. Implications include identifying
      students most in need of interventions, and tailoring interventions to target
      temporal framing in decision-making.

PMID- 25607805
TI  - Experimentally-derived fibroblast gene signatures identify molecular pathways
      associated with distinct subsets of systemic sclerosis patients in three
      independent cohorts.
AB  - Genome-wide expression profiling in systemic sclerosis (SSc) has identified four
      'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and
      normal-like), each of which shows deregulation of distinct signaling pathways;
      however, the full set of pathways contributing to this differential gene
      expression has not been fully elucidated. Here we examine experimentally derived
      gene expression signatures in dermal fibroblasts for thirteen different signaling
      pathways implicated in SSc pathogenesis. These data show distinct and overlapping
      sets of genes induced by each pathway, allowing for a better understanding of the
      molecular relationship between profibrotic and immune signaling networks. Pathway
      specific gene signatures were analyzed across a compendium of microarray datasets
      consisting of skin biopsies from three independent cohorts representing 80 SSc
      patients, 4 morphea, and 26 controls. IFNalpha signaling showed a strong
      association with early disease, while TGFbeta signaling spanned the
      fibroproliferative and inflammatory subsets, was associated with worse MRSS, and
      was higher in lesional than non-lesional skin. The fibroproliferative subset was
      most strongly associated with PDGF signaling, while the inflammatory subset
      demonstrated strong activation of innate immune pathways including TLR signaling
      upstream of NF-kappaB. The limited and normal-like subsets did not show
      associations with fibrotic and inflammatory mediators such as TGFbeta and
      TNFalpha. The normal-like subset showed high expression of genes associated with
      lipid signaling, which was absent in the inflammatory and limited subsets.
      Together, these data suggest a model by which IFNalpha is involved in early
      disease pathology, and disease severity is associated with active TGFbeta
      signaling. 

PMID- 25607808
TI  - Prioritizing--The task strategy of the powerful?
AB  - Previous research has shown that power increases focus on the main goal when
      distractor information is present. As a result, high-power people have been
      described as goal-focused. In real life, one typically wants to pursue multiple
      goals at the same time. There is a lack of research on how power affects how
      people deal with situations in which multiple important goals are present. To
      address this question, 158 participants were primed with high or low power or
      assigned to a control condition, and were asked to perform a dual-goal task with
      three difficulty levels. We hypothesized and found that high-power primed people
      prioritize when confronted with a multiple-goal situation. More specifically,
      when task demands were relatively low, power had no effect; participants
      generally pursued multiple goals in parallel. However, when task demands were
      high, the participants in the high-power condition focused on a single goal
      whereas participants in the low-power condition continued using a dual-task
      strategy. This study extends existing power theories and research in the domain
      of goal pursuit. 

PMID- 25607807
TI  - The Effect of Neighborhood Context on the Relationship Between Substance Misuse
      and Weapons Aggression in Urban Adolescents Seeking ED Care.
AB  - BACKGROUND: Frameworks for studying the ecology of human behavior suggest that
      multiple levels of the environment influence behavior and that these levels
      interact. Applied to studies of weapons aggression, this suggests proximal risk
      factor (e.g., substance use) effects may differ across neighborhoods. OBJECTIVES:
      To estimate how the association between weapons aggression and substance use
      varies as a function of several community-level variables. METHODS: Individual
      level measures (demographics, behavioral measures) were obtained from a survey of
      youth aged 14-24 years old seeking care at a Level-1 ED in Flint, Michigan.
      Community-level variables were obtained from public sources. Logistic generalized
      additive models were used to test whether community-level variables (crime rates,
      alcohol outlets, demographics) modify the link between individual-level substance
      use variables and the primary outcome measure: self-reported past 6-month weapon
      (firearm/knife) related aggression. RESULTS: The effect of marijuana misuse on
      weapons aggression varied significantly as a function of five community-level
      variables: racial composition, vacant housing rates, female headed household
      rates, density of package alcohol outlets, and nearby drug crime rates. The
      effect of high-risk alcohol use did not depend on any of the eight community
      variables tested. CONCLUSIONS: The relationship between marijuana misuse and
      weapons aggression differed across neighborhoods with generally less association
      in more disadvantaged neighborhoods, while high-risk alcohol use showed a
      consistently high association with weapons aggression that did not vary across
      neighborhoods. The results aid in understanding the contributions of alcohol and
      marijuana use to the etiology of weapon-related aggression among urban youth, but
      further study in the general population is required.

PMID- 25607810
TI  - MicroRNA-133a inhibits cell proliferation, colony formation ability, migration
      and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma.
AB  - MicroRNA-133a (miR-133a) is downregulated in various types of human malignancy,
      including hepatocellular carcinoma (HCC), renal cell carcinoma, esophageal
      squamous cell carcinoma, bladder cancer, ileal carcinoid and rhabdomyosarcoma.
      The aim of the present study was to examine the effects of miR-133a on HCC cell
      proliferation, colony formation, migration and invasion. miR-133a was transfected
      into the HCC HepG2 and SMMC-7721 cell lines and the expression levels of miR-133a
      were determined; in addition, cell viability assays, colony formation assays,
      cell migration assays, cell invasion assays, western blot analyses and luciferase
      assays were performed in the HCC cell lines. The results demonstrated that miR
      133a significantly inhibited cell proliferation, colony formation, migration and
      invasion in HepG2 and SMMC-7721 cells. To the best of our knowledge, the present
      study also provided the first evidence that miR-133a directly downregulated the
      expression of matrix metallopeptidase 9 (MMP-9) in the HCC cells. In conclusion,
      the results of the present study indicated that miR-133a may have suppressed cell
      proliferation, colony formation, migration and invasion via the downregulation of
      MMP-9 in HCC cell lines. Therefore, MMP-9 may be used for the development of
      novel molecular markers and therapeutic approaches to inhibit hepatocellular
      carcinoma metastasis.

PMID- 25607811
TI  - Characterization of phospholipids by two-dimensional liquid chromatography
      coupled to in-line ozonolysis-mass spectrometry.
AB  - In this study, the characterization of phospholipids (PL) was achieved by using a
      combination of LC/MS/MS and two-dimensional LC/MS. A HILIC LC column was used for
      PL class separation, while the further molecular species separation of each PL
      class was achieved by using online HILIC * C18 LC. The double bond positions
      along the fatty acyl chains of these PL molecular species were also obtained by
      using the combination of 2D-LC and in-line ozonolysis-MS analysis. The ozonolysis
      device is composed of a gas-permeable, liquid-impermeable Teflon tube passing
      through a glass chamber filled with ozone gas, which is then placed in-line
      between the 2D-LC and the mass spectrometer. The eluting PL molecules in the LC
      mobile phase passed through the device where they rapidly reacted with the ozone
      that penetrated through the tubing wall. The ozonolysis products were then
      detected by MS in real-time, which allowed the localization of the double bonds
      along the fatty acyl chains in these PL molecular species. This comprehensive
      method was successfully applied to an egg yolk PL extract, which revealed the
      detailed structures of the PL molecules.

PMID- 25607812
TI  - Nanoporous silica-based protocells at multiple scales for designs of life and
      nanomedicine.
AB  - Various protocell models have been constructed de novo with the bottom-up
      approach. Here we describe a silica-based protocell composed of a nanoporous
      amorphous silica core encapsulated within a lipid bilayer built by self-assembly
      that provides for independent definition of cell interior and the surface
      membrane. In this review, we will first describe the essential features of this
      architecture and then summarize the current development of silica-based
      protocells at both micro- and nanoscale with diverse functionalities. As the
      structure of the silica is relatively static, silica-core protocells do not have
      the ability to change shape, but their interior structure provides a highly
      crowded and, in some cases, authentic scaffold upon which biomolecular components
      and systems could be reconstituted. In basic research, the larger protocells
      based on precise silica replicas of cells could be developed into geometrically
      realistic bioreactor platforms to enable cellular functions like coupled
      biochemical reactions, while in translational research smaller protocells based
      on mesoporous silica nanoparticles are being developed for targeted nanomedicine.
      Ultimately we see two different motivations for protocell research and
      development: (1) to emulate life in order to understand it; and (2) to use
      biomimicry to engineer desired cellular interactions. 

PMID- 25607814
TI  - Telling faces together: Learning new faces through exposure to multiple
      instances.
AB  - We are usually able to recognize novel instances of familiar faces with little
      difficulty, yet recognition of unfamiliar faces can be dramatically impaired by
      natural within-person variability in appearance. In a card-sorting task for
      facial identity, different photos of the same unfamiliar face are often seen as
      different people. Here we report two card-sorting experiments in which we
      manipulate whether participants know the number of identities present. Without
      constraints, participants sort faces into many identities. However, when told the
      number of identities present, they are highly accurate. This minimal contextual
      information appears to support viewers in "telling faces together". In Experiment
      2 we show that exposure to within-person variability in the sorting task improves
      performance in a subsequent face-matching task. This appears to offer a fast
      route to learning generalizable representations of new faces. 

PMID- 25607813
TI  - How amino acids and peptides shaped the RNA world.
AB  - The "RNA world" hypothesis is seen as one of the main contenders for a viable
      theory on the origin of life. Relatively small RNAs have catalytic power, RNA is
      everywhere in present-day life, the ribosome is seen as a ribozyme, and rRNA and
      tRNA are crucial for modern protein synthesis. However, this view is incomplete
      at best. The modern protein-RNA ribosome most probably is not a distorted form of
      a "pure RNA ribosome" evolution started out with. Though the oldest center of the
      ribosome seems "RNA only", we cannot conclude from this that it ever functioned
      in an environment without amino acids and/or peptides. Very small RNAs (versatile
      and stable due to basepairing) and amino acids, as well as dipeptides, coevolved.
      Remember, it is the amino group of aminoacylated tRNA that attacks peptidyl-tRNA,
      destroying the bond between peptide and tRNA. This activity of the amino acid
      part of aminoacyl-tRNA illustrates the centrality of amino acids in life. With
      the rise of the "RNA world" view of early life, the pendulum seems to have swung
      too much towards the ribozymatic part of early biochemistry. The necessary
      presence and activity of amino acids and peptides is in need of highlighting. In
      this article, we try to bring the role of the peptide component of early life
      back into focus. We argue that an RNA world completely independent of amino acids
      never existed. 

PMID- 25607815
TI  - Effects of customized balance exercises on older women whose balance ability has
      deteriorated with age.
AB  - Falls represent a major public health problem for older adults, and loss of
      balance (LOS) abilities is one of the primary causes of falls. Previous studies
      have shown that balance training is effective in improving physical function and
      decreasing risk of falls. However, little attention has been given specifically
      to balance training in older adults with very poor balance. The purpose of this
      study was to determine the effect of a 12-week customized balance exercise
      program on LOS for community-dwelling older women with poor balance ability.
      Twenty-four older women with poor balance (composite maximum excursion [MXEcomp]
      score of less than 70% based on Limits of Stability) were divided into an
      exercise group and control group. After 12 weeks of balance exercises, mean
      MXEcomp improved (p < .05) from 58.6% to 79.0% in the exercise group. EPEcomp
      (composite endpoint excursion), RTcomp (composite reaction time), SVcomp3
      (composite sway velocity on thick foam with the eyes open), UG (up and go) also
      improved, but the functional reach and other static balance indexes did not
      change. These results indicated that balance training allows older adults with
      poor balance to improve dynamic balance ability and potentially reduce risk for
      falls.

PMID- 25607816
TI  - Predicting Health Care Cost Transitions Using a Multidimensional Adaptive
      Prediction Process.
AB  - Managing population health requires meeting individual care needs while striving
      for increased efficiency and quality of care. Predictive models can integrate
      diverse data to provide objective assessment of individual prospective risk to
      identify individuals requiring more intensive health management in the present.
      The purpose of this research was to develop and test a predictive modeling
      approach, Multidimensional Adaptive Prediction Process (MAPP). MAPP is predicated
      on dividing the population into cost cohorts and then utilizing a collection of
      models and covariates to optimize future cost prediction for individuals in each
      cohort. MAPP was tested on 3 years of administrative health care claims starting
      in 2009 for health plan members (average n=25,143) with evidence of coronary
      heart disease. A "status quo" reference modeling methodology applied to the total
      annual population was established for comparative purposes. Results showed that
      members identified by MAPP contributed $7.9 million and $9.7 million more in 2011
      health care costs than the reference model for cohorts increasing in cost or
      remaining high cost, respectively. Across all cohorts, the additional accurate
      cost capture of MAPP translated to an annual difference of $1882 per member, a
      21% improvement, relative to the reference model. The results demonstrate that
      improved future cost prediction is achievable using a novel adaptive multiple
      model approach. Through accurate prospective identification of individuals whose
      costs are expected to increase, MAPP can help health care entities achieve
      efficient resource allocation while improving care quality for emergent need
      individuals who are intermixed among a diverse set of health care consumers.

PMID- 25607817
TI  - Synthesis and characterization of ferrocene-chelating heteroscorpionate complexes
      of nickel(II) and zinc(II).
AB  - The first example of a ferrocene-chelating heteroscorpionate,
      [Li(THF)2][fc(PPh2)(BH[(3,5-Me)2pz]2)] ((fc(P,B))Li(THF)2, fc = 1,1'
      ferrocenediyl) is described. Starting from a previously reported compound,
      fcBr(PPh2), a series of ferrocene derivatives, fc(PPh2)(B[OMe]2),
      [Li(OEt2)][fc(PPh2)(BH3)], [Li(THF)2][fc(PPh2)(BH[(3,5-Me)2pz]2)] (pz =
      pyrazole), was isolated and characterized. Compound (fc(P,B))Li(THF)2 allowed the
      synthesis of the corresponding nickel and zinc complexes, (fc(P,B))NiCl,
      (fc(P,B))NiMe, (fc(P,B))ZnCl, and (fc(P,B))ZnMe. All compounds were characterized
      by NMR spectroscopy, while the zinc and nickel complexes were also characterized
      by X-ray crystallography. The redox behavior of (fc(P,B))NiCl, (fc(P,B))NiMe,
      (fc(P,B))ZnCl, and (fc(P,B))ZnMe was studied by cyclic voltammetry and supported
      by density functional theory calculations. 

PMID- 25607818
TI  - The familial basis of facial emotion recognition deficits in adolescents with
      conduct disorder and their unaffected relatives.
AB  - BACKGROUND: There is accumulating evidence of impairments in facial emotion
      recognition in adolescents with conduct disorder (CD). However, the majority of
      studies in this area have only been able to demonstrate an association, rather
      than a causal link, between emotion recognition deficits and CD. To move closer
      towards understanding the causal pathways linking emotion recognition problems
      with CD, we studied emotion recognition in the unaffected first-degree relatives
      of CD probands, as well as those with a diagnosis of CD. METHOD: Using a family
      based design, we investigated facial emotion recognition in probands with CD (n =
      43), their unaffected relatives (n = 21), and healthy controls (n = 38). We used
      the Emotion Hexagon task, an alternative forced-choice task using morphed facial
      expressions depicting the six primary emotions, to assess facial emotion
      recognition accuracy. RESULTS: Relative to controls, the CD group showed impaired
      recognition of anger, fear, happiness, sadness and surprise (all p < 0.005).
      Similar to probands with CD, unaffected relatives showed deficits in anger and
      happiness recognition relative to controls (all p < 0.008), with a trend toward a
      deficit in fear recognition. There were no significant differences in performance
      between the CD probands and the unaffected relatives following correction for
      multiple comparisons. CONCLUSIONS: These results suggest that facial emotion
      recognition deficits are present in adolescents who are at increased familial
      risk for developing antisocial behaviour, as well as those who have already
      developed CD. Consequently, impaired emotion recognition appears to be a viable
      familial risk marker or candidate endophenotype for CD.

PMID- 25607820
TI  - Dynamics of high-speed micro-drop impact: numerical simulations and experiments
      at frame-to-frame times below 100 ns.
AB  - Technologies including (3D-) (bio-)printing, diesel engines, laser-induced
      forward transfer, and spray cleaning require optimization and therefore
      understanding of micrometer-sized droplets impacting at velocities beyond 10 m s(
      1). However, as yet, this regime has hardly been addressed. Here we present the
      first time-resolved experimental investigation of microdroplet impact at
      velocities up to V0 = 50 m s(-1), on hydrophilic and -phobic surfaces at frame
      rates exceeding 10(7) frames per second. A novel method to determine the 3D
      droplet profile at sub-micron resolution at the same frame rates is presented,
      using the fringe pattern observed from a bottom view. A numerical model, which is
      validated by the side- and bottom-view measurements, is employed to study the
      viscous boundary layer inside the droplet and the development of the rim. The
      spreading dynamics, the maximal spreading diameter, the boundary layer thickness,
      the rim formation, and the air bubble entrainment are compared to theory and
      previous experiments. In general, the impact dynamics are equal to millimeter
      sized droplet impact for equal Reynolds-, Weber- and Stokes numbers (Re, We, and
      St, respectively). Using our numerical model, effective scaling laws for the
      progression of the boundary layer thickness and the rim diameter are provided.
      The dimensionless boundary layer thickness develops in time (t) according to
      deltaBL ~ D0/?Re(t/tau)0.45, and the diameter of the rim develops as DRim ~
      D0/?We(t/tau)0.68, with drop diameter D0 and inertial time scale tau = D0/V0.
      These scalings differ from previously assumed, but never validated, values.
      Finally, no splash is observed, at variance with many predictions but in
      agreement with models including the influence of the surrounding gas. This
      confirms that the ambient gas properties are key ingredients for splash threshold
      predictions.

PMID- 25607819
TI  - Dense collagen-I matrices enhance pro-tumorigenic estrogen-prolactin crosstalk in
      MCF-7 and T47D breast cancer cells.
AB  - Breast cancers that express estrogen receptor alpha (ERalpha+) constitute the
      majority of breast tumors. Estrogen is a major driver of their growth, and
      targeting ER-mediated signals is a largely successful primary therapeutic
      strategy. Nonetheless, ERalpha+ tumors also result in the most breast cancer
      mortalities. Other factors, including altered characteristics of the
      extracellular matrix such as density and orientation and consequences for
      estrogen crosstalk with other hormones such as prolactin (PRL), may contribute to
      these poor outcomes. Here we employed defined three dimensional low
      density/compliant and high density/stiff collagen-I matrices to investigate the
      effects on 17beta-estradiol (E2) activity and PRL/E2 interactions in two well
      characterized ERalpha+/PRLR+ luminal breast cancer cell lines in vitro. We
      demonstrate that matrix density modulated E2-induced transcripts, but did not
      alter the growth response. However, matrix density was a potent determinant of
      the behavioral outcomes of PRL/E2 crosstalk. High density/stiff matrices enhanced
      PRL/E2-induced growth mediated by increased activation of Src family kinases and
      insensitivity to the estrogen antagonist, 4-hydroxytamoxifen. It also permitted
      these hormones in combination to drive invasion and modify the alignment of
      collagen fibers. In contrast, low density/compliant matrices allowed modest if
      any cooperation between E2 and PRL to growth and did not permit hormone-induced
      invasion or collagen reorientation. Our studies demonstrate the power of matrix
      density to determine the outcomes of hormone actions and suggest that stiff
      matrices are potent collaborators of estrogen and PRL in progression of ERalpha+
      breast cancer. Our evidence for bidirectional interactions between these hormones
      and the extracellular matrix provides novel insights into the regulation of the
      microenvironment of ERalpha+ breast cancer and suggests new therapeutic
      approaches. 

PMID- 25607821
TI  - Hepatic expression of the Sptlc3 subunit of serine palmitoyltransferase is
      associated with the development of hepatocellular carcinoma in a mouse model of
      nonalcoholic steatohepatitis.
AB  - The molecular mechanisms underlying the progression of nonalcoholic
      steatohepatitis (NASH) have not been fully elucidated. The aim of this study was
      to identify factors involved in NASH progression by analysis of
      pathophysiological features and gene-expression profiles in livers of STAM mice,
      a model of NASH-associated hepatocarcinogenesis. C57BL/6N (B6N) mice were
      injected with streptozotocin to generate STAM mice. Four-week-old male STAM and
      B6N mice were fed a high-fat diet (HFD) (STAM-F, B6N-F) or a conventional diet
      (STAM-C, B6N-C) until they were 10, 14, or 18 weeks old. Blood glucose and
      nonalcoholic fatty liver disease (NAFLD) activity scores of STAM-F were higher
      than those of STAM-C during all observation periods. STAM-F mice had more severe
      hepatic fibrosis at 14 weeks, and exhibited higher levels of alpha-fetoprotein
      positive hepatic tumor formation with multiplication than STAM-C mice at 18
      weeks. At 14 weeks, cDNA microarray analysis revealed that the hepatic expression
      of eight mRNAs was >=30-fold higher in STAM-F than B6N-F mice. The expression of
      another four genes was increased >=5-fold in STAM-F than B6N-F mice, and >=5-fold
      in B6N-F relative to B6N-C mice. Of the 12 genes, the difference in Sptlc3 mRNA
      expression was most pronounced, and gradually increased over time, as determined
      by quantitative RT-PCR in STAM-F mice. In addition, Sptlc3 mRNA expression in
      STAM-F mice was higher than that in db/db mice that received HFD and in B6N mice
      fed a choline-deficient L-amino acid (CDAA)-defined diet. In conclusion, a high
      fat diet aggravated pathophysiological findings in the liver in NASH mouse
      models, and the hepatic expression of Sptlc3 mRNA was potentially associated with
      NASH progression. 

PMID- 25607822
TI  - Key factors for stable retention of fluorophores and labeled biomolecules in
      droplet-based microfluidics.
AB  - Water-in-oil emulsion droplets created in droplet-based microfluidic devices have
      been tested and used recently as well-defined picoliter-sized 3D compartments for
      various biochemical and biomedical applications. In many of these applications,
      fluorescence measurements are applied to reveal the protein content, spatial
      distribution, and dynamics in the droplets. However, emulsion droplets do not
      always provide entirely sealed compartments, and partitioning of dyes or labeled
      molecules to the oil phase is frequently observed. Therefore, stable molecular
      retention in the droplets represents a challenge, and many physical and chemical
      key factors of microfluidic system components have to be considered. In this
      study, we investigated the retention of 12 commonly used water-soluble dyes in
      droplets having six different aqueous phase conditions. We demonstrate that the
      physicochemical properties of the dyes have a major influence on the retention
      level. In particular, hydrophilicity has a strong influence on retention, with
      highly hydrophilic dyes (LogD < -7) showing stable, buffer/medium independent
      retention. In the case of less hydrophilic dyes, we showed that retention can be
      improved by adjusting the surfactants physical properties, such as geometry,
      length, and concentration. Furthermore, we analyzed the retention stability of
      labeled biomolecules such as antibodies, streptavidin, and tubulin proteins and
      showed that stable retention can be strongly dependent on dye and surfactants
      selection. 

PMID- 25607824
TI  - The impacts of electricity dispatch protocols on the emission reductions due to
      wind power and carbon tax.
AB  - Two dispatch protocols have been adopted by electricity markets to deal with the
      uncertainty of wind power but the effects of the selection between the dispatch
      protocols have not been comprehensively analyzed. We establish a framework to
      compare the impacts of adopting different dispatch protocols on the efficacy of
      using wind power and implementing a carbon tax to reduce emissions. We suggest
      that a market has high potential to achieve greater emission reduction by
      adopting the stochastic dispatch protocol instead of the static protocol when the
      wind energy in the market is highly uncertain or the market has enough adjustable
      generators, such as gas-fired combustion generators. Furthermore, the carbon-tax
      policy is more cost-efficient for reducing CO2 emission when the market operates
      according to the stochastic protocol rather than the static protocol. An
      empirical study, which is calibrated according to the data from the Electric
      Reliability Council of Texas market, confirms that using wind energy in the Texas
      market results in a 12% CO2 emission reduction when the market uses the
      stochastic dispatch protocol instead of the 8% emission reduction associated with
      the static protocol. In addition, if a 6$/ton carbon tax is implemented in the
      Texas market operated according to the stochastic protocol, the CO2 emission is
      similar to the emission level from the same market with a 16$/ton carbon tax
      operated according to the static protocol. Correspondingly, the 16$/ton carbon
      tax associated with the static protocol costs 42.6% more than the 6$/ton carbon
      tax associated with the stochastic protocol. 

PMID- 25607823
TI  - Serum amyloid a truncations in type 2 diabetes mellitus.
AB  - METHODS: Using mass spectrometric immunoassay, the abundance of SAA truncations
      relative to the native variants was examined in plasma of 91 participants with
      type 2 diabetes and chronic kidney disease and 69 participants without diabetes.
      RESULTS: The ratio of SAA 1.1 (missing N-terminal arginine) to native SAA 1.1 was
      lower in diabetics compared to non-diabetics (p = 0.004), and in males compared
      to females (p<0.001). This ratio was negatively correlated with glycated
      hemoglobin (r = -0.32, p<0.001) and triglyceride concentrations (r = -0.37,
      p<0.001), and positively correlated with HDL cholesterol concentrations (r =
      0.32, p<0.001). CONCLUSION: The relative abundance of the N-terminal arginine
      truncation of SAA1.1 is significantly decreased in diabetes and negatively
      correlates with measures of glycemic and lipid control.

PMID- 25607825
TI  - Photocurrent enhanced by singlet fission in a dye-sensitized solar cell.
AB  - Investigations of singlet fission have accelerated recently because of its
      potential utility in solar photoconversion, although only a few reports
      definitively identify the role of singlet fission in a complete solar cell.
      Evidence of the influence of singlet fission in a dye-sensitized solar cell using
      1,3-diphenylisobenzofuran (DPIBF, 1) as the sensitizer is reported here. Self
      assembly of the blue-absorbing 1 with co-adsorbed oxidation products on
      mesoporous TiO2 yields a cell with a peak internal quantum efficiency of ~70% and
      a power conversion efficiency of ~1.1%. Introducing a ZrO2 spacer layer of
      thickness varying from 2 to 20 A modulates the short-circuit photocurrent such
      that it is initially reduced as thickness increases but 1 with 10-15 A of added
      ZrO2. This rise can be explained as being due to a reduced rate of injection of
      electrons from the S1 state of 1 such that singlet fission, known to occur with a
      30 ps time constant in polycrystalline films, has the opportunity to proceed
      efficiently and produce two T1 states per absorbed photon that can subsequently
      inject electrons into TiO2. Transient spectroscopy and kinetic simulations
      confirm this novel mode of dye-sensitized solar cell operation and its potential
      utility for enhanced solar photoconversion. 

PMID- 25607826
TI  - To resume a stalled psychotherapy? Psychological testing to understand an impasse
      and reevaluate treatment options.
AB  - Clinical wisdom holds that psychological testing is a useful tool for
      consultation when there is a need to untangle and resolve a psychotherapeutic
      impasse. However, there has been a lack of empirical research in this area, and
      only a few cases have been published demonstrating how psychological testing can
      be used toward this end. In this article, the author offers a case illustration
      of the application of testing with a patient who sought to resume psychotherapy
      following a previous impasse and premature termination. Specific referral
      questions for the evaluation are explicated followed by discussion of the test
      data that answered each of them. The findings pointed not only to intrapsychic
      and object relational characteristics of the patient that contributed to the
      impasse but, importantly, alerted the author-therapist to his contributions as
      well. Treatment implications of the findings are also highlighted. 

PMID- 25607827
TI  - Decreased microRNA-132 and its function in human non-small cell lung cancer.
AB  - MicroRNA-132 (miR-132) has been shown to be dysregulated in certain types of
      human malignancies and is associated with tumor progression. However, its
      function in non-small cell lung cancer (NSCLC) and whether it is differentially
      expressed in this disease, remain unclear. Thus, the aim of the present study was
      to investigate the effects of miR-132 on NSCLC tumorigenesis and progression.
      Using reverse transcription-quantitative polymerase chain reaction, miR-132
      expression was detected in NSCLC cell lines and primary tumor tissues. The
      association between miR-132 expression, and clinicopathological factors and
      prognosis was assessed using statistical analysis. An MTT assay, flow cytometry,
      Transwell invasion assays and scratch migration assays were conducted in order to
      examine the proliferation, apoptosis, invasion and migration of NSCLC cells that
      had been transfected with miR-132 mimics or inhibitors. The results showed that
      miR-132 expression levels were significantly downregulated in NSCLC cells
      compared with that in corresponding non-cancerous lung tissues (P<0.001). In
      addition, reduced miR-132 expression was significantly associated with lymph node
      metastasis (P=0.003), an advanced tumor-node-metastasis stage (P<0.001) and
      shorter overall survival (P<0.001). Multivariate regression analysis confirmed
      that downregulation of miR-132 was an independent predictor of prognosis.
      Furthermore, transfection of miR-132 mimics into the NSCLC cells reduced cell
      proliferation, invasion and migration, and promoted cell apoptosis. These
      findings indicate that miR-132 may be a novel diagnostic and prognostic marker,
      as well as a potential target for molecular therapy in NSCLC.

PMID- 25607828
TI  - Indications and limitations of afamelanotide for treating vitiligo-reply.

PMID- 25607829
TI  - Antibiotic Resistance Prevalence in Routine Bloodstream Isolates from Children's
      Hospitals Varies Substantially from Adult Surveillance Data in Europe.
AB  - BACKGROUND: Surveillance of antimicrobial resistance (AMR) is central for
      defining appropriate strategies to deal with changing AMR levels. It is unclear
      whether childhood AMR patterns differ from those detected in isolates from adult
      patients. METHODS: Resistance percentages of nonduplicate Staphylococcus aureus,
      Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium,
      Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa bloodstream
      isolates from children less than 18 years of age reported to the Antibiotic
      Resistance and Prescribing in European Children (ARPEC) project were compared
      with all-age resistance percentages reported by the European Antimicrobial
      Resistance Surveillance Network (EARS-Net) for the same pathogen-antibiotic class
      combinations, period and countries. In addition, resistance percentages were
      compared between ARPEC isolates from children less than 1 year of age and
      children greater than or equal to1 year of age. RESULTS: Resistance percentages
      for many important pathogen-antibiotic class combinations were different for
      ARPEC isolates compared with EARS-Net. E. coli and K. pneumoniae fluoroquinolone
      resistance percentages were substantially lower in ARPEC (13.4% and 17.9%) than
      in EARS-Net (23.0% and 30.7%), whereas the reverse was true for all pathogen
      antibiotic class combinations in P. aeruginosa (for example, 27.3% aminoglycoside
      resistance in ARPEC, 19.3% in EARS-Net, 32.8% carbapenem resistance in ARPEC and
      20.5% in EARS-Net), and for S. pneumoniae and macrolide resistance. For many Gram
      negative pathogen-antibiotic class combinations, isolates from children greater
      than or equal to 1 year of age showed higher resistance percentages than isolates
      from children less than 1 year of age. CONCLUSIONS: Age-stratified presentation
      of resistance percentage estimates by surveillance programs will allow
      identification of important variations in resistance patterns between different
      patient groups for targeted intervention.

PMID- 25607830
TI  - Biosynthesis of copper nanoparticles and its effect on actively dividing cells of
      mitosis in Allium cepa.
AB  - Nanobiotechnological application of copper nanoparticles has paved the way for
      advancement in agriculture owing to its bactericidal and fungicidal activities.
      Recently, researchers have focussed on bioinspired synthesis of copper
      nanoparticles as a viable alternative to existing physicochemical techniques. For
      the commercialization of nanocopper, the toxicity evaluation is a major issue. In
      this context, Citrus medica (L.) fruit extract-mediated copper nanoparticles were
      synthesized and its different concentrations (10, 20, 40, 60, 80, and 100 ug mL(
      1) ) were evaluated for its effect on actively dividing cells of Allium cepa. The
      study clearly revealed that copper nanoparticles increased mitotic index up to
      the concentration of 20 ug mL(-1) . In addition, a gradual decline in mitotic
      index and increase in abnormality index was observed as the concentration of
      copper nanoparticles and treatment duration were increased. Aberrations in
      chromosomal behavior such as sticky and disturbed chromosomes in metaphase and
      anaphase, c-metaphase, bridges, laggard, disturbed telophase, and vacuolated
      nucleus were also observed.

PMID- 25607831
TI  - CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast
      cancer cell line by the ROS/JNK signaling pathway.
AB  - Cyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is
      an enzyme which post-synthetically converts the RNA modification N6-iso
      pentenyladenosine (i6A) into 2-methylthio-N6-isopentenyladenosine (ms2i6A).
      However, the interaction between CDK5RAP1 deficiency and cell apoptosis has not
      been studied. Breast cancer has long been a leading cause of mortality in the
      world. Therefore, in the present study, CDK5RAP1 deficiency in a human breast
      cancer cell line was investigated. CDK5RAP1 small interfering RNA (siRNA) and
      negative control siRNA were transfected into MCF-7 cells, and the cells were
      further incubated for 48 h. CDK5RAP1 deficiency suppressed tumor growth in MCF-7
      cells and arrested the cells at G2/M phase. CDK5RAP1 deficiency also induced cell
      apoptosis and reactive oxygen species (ROS) generation. Furthermore, western blot
      analysis showed that the expression of phospho-c-Jun N-terminal kinase (p-JNK),
      p53, caspase-9 and caspase-3 were upregulated in CDK5RAP1-deficient MCF-7 cells.
      Pretreatment with N-acetyl-cysteine (NAC), the inhibitor of ROS, or with
      SP600125, the inhibitor of JNK, prevented the apoptosis and the high expression
      of p-JNK, p53, caspase-9 and caspase-3 in CDK5RAP1-deficient MCF-7 cells. Taken
      together, these data indicated that CDK5RAP1 deficiency induced cell cycle arrest
      and apoptosis in human breast cancer MCF-7 cells by the ROS/JNK signaling
      pathway. Our findings indicated a novel therapeutic strategy for cancer.

PMID- 25607832
TI  - Excited state dynamics of organic semi-conducting materials.
AB  - Time-resolved absorption and emission spectroscopy has been applied to
      investigate the dynamics of excited state processes in oligomer models for semi
      conducting organic materials. Following the photo-excitation of a pentamer
      oligomer that is a model for the conjugated polymer MEH-PPV, an ultrafast
      component of a few picoseconds is observed for the decay of the initially formed
      transient species. Variable temperature absorption and emission spectra combined
      with X-ray crystallography and calculations support the assignment of this rapid
      relaxation process to an excited state conformational rearrangement from non
      planar to more planar molecular configurations. The implications of the results
      for the overall photophysics of conjugated polymers are considered. 

PMID- 25607833
TI  - Prolonged exposure vs eye movement desensitization and reprocessing vs waiting
      list for posttraumatic stress disorder in patients with a psychotic disorder: a
      randomized clinical trial.
AB  - IMPORTANCE: The efficacy of posttraumatic stress disorder (PTSD) treatments in
      psychosis has not been examined in a randomized clinical trial to our knowledge.
      Psychosis is an exclusion criterion in most PTSD trials. OBJECTIVE: To examine
      the efficacy and safety of prolonged exposure (PE) therapy and eye movement
      desensitization and reprocessing (EMDR) therapy in patients with psychotic
      disorders and comorbid PTSD. DESIGN, SETTING, AND PARTICIPANTS: A single-blind
      randomized clinical trial with 3 arms (N = 155), including PE therapy, EMDR
      therapy, and waiting list (WL) of 13 outpatient mental health services among
      patients with a lifetime psychotic disorder and current chronic PTSD. Baseline,
      posttreatment, and 6-month follow-up assessments were made. INTERVENTIONS:
      Participants were randomized to receive 8 weekly 90-minute sessions of PE (n =
      53), EMDR (n = 55), or WL (n = 47). Standard protocols were used, and treatment
      was not preceded by stabilizing psychotherapeutic interventions. MAIN OUTCOMES
      AND MEASURES: Clinician-rated severity of PTSD symptoms, PTSD diagnosis, and full
      remission (on the Clinician-Administered PTSD Scale) were primary outcomes. Self
      reported PTSD symptoms and posttraumatic cognitions were secondary outcomes.
      RESULTS: Data were analyzed as intent to treat with linear mixed models and
      generalized estimating equations. Participants in the PE and EMDR conditions
      showed a greater reduction of PTSD symptoms than those in the WL condition.
      Between-group effect sizes were 0.78 (P < .001) in PE and 0.65 (P = .001) in
      EMDR. Participants in the PE condition (56.6%; odds ratio [OR], 3.41; P = .006)
      or the EMDR condition (60.0%; OR, 3.92; P < .001) were significantly more likely
      to achieve loss of diagnosis during treatment than those in the WL condition
      (27.7%). Participants in the PE condition (28.3%; OR, 5.79; P = .01), but not
      those in the EMDR condition (16.4%; OR, 2.87; P = .10), were more likely to gain
      full remission than those in the WL condition (6.4%). Treatment effects were
      maintained at the 6-month follow-up in PE and EMDR. Similar results were obtained
      regarding secondary outcomes. There were no differences in severe adverse events
      between conditions (2 in PE, 1 in EMDR, and 4 in WL). The PE therapy and EMDR
      therapy showed no difference in any of the outcomes and no difference in
      participant dropout (24.5% in PE and 20.0% in EMDR, P = .57). CONCLUSIONS AND
      RELEVANCE: Standard PE and EMDR protocols are effective, safe, and feasible in
      patients with PTSD and severe psychotic disorders, including current symptoms. A
      priori exclusion of individuals with psychosis from evidence-based PTSD
      treatments may not be justifiable. TRIAL REGISTRATION: isrctn.com Identifier:
      ISRCTN79584912.

PMID- 25607834
TI  - In vivo analysis of lung cancer metabolism: nothing like the real thing.
AB  - Cancer cells exhibit altered metabolism compared with that of the surrounding
      tissue. There is hope that these reprogrammed metabolic pathways in tumors hold
      the key to advances for both cancer imaging and therapy. Translation of
      observations in cultured cancer cells to live tumors, however, has proven to be
      highly complex, and robust methods to analyze metabolic activity in primary human
      tumors are sorely needed. In this issue of the JCI, Sellers et al. use
      perioperative administration of isotope-labeled glucose to lung cancer patients
      to differentiate metabolic pathways between tumors and benign lung. They identify
      pyruvate carboxylation, a reaction that enables glucose-derived carbon to
      replenish TCA cycle intermediates, as a key component of anabolic metabolism in
      tumor cells. 

PMID- 25607835
TI  - Role reversal: infiltrating T cells protect the brain.
AB  - Inflammatory conditions intensify and then resolve, often sparing and recovering
      some of the injured tissue. While the ebb and flow of inflammation can be
      followed in many tissues, there is not a great deal of information on how
      inflammation regresses in the brain. In this issue of the JCI, Walsh, Hendrix,
      and colleagues illuminate a cellular mechanism whereby T cells that infiltrate
      the brain after nerve crush or contusion actually protect neurons from injury.
      These infiltrating T cells produce IL-4 and do so independently of a classic
      adaptive T cell immune response. The T cells respond to mediators produced by
      damaged neurons, without the classic three-way interaction among antigen, the
      major histocompatibility complex, and the T cell receptor. After brain injury,
      these protective T cells produce IL-4, which attenuates damage via IL-4 receptors
      on neurons. 

PMID- 25607836
TI  - Fighting polyglutamine disease by wrestling with SUMO.
AB  - Spinobulbar muscular atrophy (SBMA) is an X-linked disease characterized by
      degeneration of motor neurons, muscle atrophy, and progressive weakness. It is
      caused by a polyglutamine (polyQ) expansion in the androgen receptor (AR), a
      transcription factor that is activated upon hormone binding. The polyQ expansion
      in AR causes it to form intracellular aggregates and impairs transcriptional
      activity. Intriguingly, SUMOylation (where SUMO indicates small ubiquitin-like
      modifier) of AR inhibits its transcriptional activity and reduces aggregation of
      the polyQ form of this protein, but it is unclear whether SUMOylation plays a
      pathogenic or protective role in SBMA. In this issue of the JCI, Chua et al.
      address this question by generating knockin mice in which the native AR is
      replaced by either a polyQ AR or a polyQ AR lacking the two lysine residues that
      are SUMOylated. The results from this study demonstrate that inhibiting
      SUMOylation of polyQ AR restores much of its transcriptional activity and
      prevents many (but not all) SBMA-associated symptoms in this mouse model. 

PMID- 25607837
TI  - Ghrelin and hypothalamic development: too little and too much of a good thing.
AB  - Neural centers in the hypothalamus regulate food intake and body weight in
      response to hormones and other neural stimuli, and dysfunctional communication
      between the brain and gut underlies metabolic disorders, including obesity. In
      this issue of the JCI, Steculorum and colleagues present evidence that the
      gastric peptide ghrelin mediates neural fiber growth in the arcuate nucleus of
      the hypothalamus during the neonatal period. Neonatal mice subjected to either
      increased or decreased ghrelin action during this developmental period had an
      increased risk of obesity in adulthood. Together, the results of this study
      support a model whereby neural organization at key stages of development sets the
      foundation for metabolic health later in life. 

PMID- 25607838
TI  - Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute
      kidney injury.
AB  - Acute kidney injury (AKI) is a public health concern with an annual mortality
      rate that exceeds those of breast and prostate cancer, heart failure, and
      diabetes combined. Oxidative stress and mitochondrial damage are drivers of AKI
      associated pathology; however, the pathways that mediate these events are poorly
      defined. Here, using a murine cisplatin-induced AKI model, we determined that
      both oxidative stress and mitochondrial damage are associated with reduced levels
      of renal sirtuin 3 (SIRT3). Treatment with the AMPK agonist AICAR or the
      antioxidant agent acetyl-l-carnitine (ALCAR) restored SIRT3 expression and
      activity, improved renal function, and decreased tubular injury in WT animals,
      but had no effect in Sirt3-/- mice. Moreover, Sirt3-deficient mice given
      cisplatin experienced more severe AKI than WT animals and died, and neither AICAR
      nor ALCAR treatment prevented death in Sirt3-/- AKI mice. In cultured human
      tubular cells, cisplatin reduced SIRT3, resulting in mitochondrial fragmentation,
      while restoration of SIRT3 with AICAR and ALCAR improved cisplatin-induced
      mitochondrial dysfunction. Together, our results indicate that SIRT3 is
      protective against AKI and suggest that enhancing SIRT3 to improve mitochondrial
      dynamics has potential as a strategy for improving outcomes of renal injury. 

PMID- 25607839
TI  - Vector design influences hepatic genotoxicity after adeno-associated virus gene
      therapy.
AB  - The use of adeno-associated virus (AAV) as a gene therapy vector has been
      approved recently for clinical use and has demonstrated efficacy in a growing
      number of clinical trials. However, the safety of AAV as a vector has been
      challenged by a single study that documented hepatocellular carcinoma (HCC) after
      AAV gene delivery in mice. Most studies have not noted genotoxicity following AAV
      mediated gene delivery; therefore, the possibility that there is an association
      between AAV and HCC is controversial. Here, we performed a comprehensive study of
      HCC in a large number of mice following therapeutic AAV gene delivery. Using a
      sensitive high-throughput integration site-capture technique and global
      expressional analysis, we found that AAV integration into the RNA imprinted and
      accumulated in nucleus (Rian) locus, and the resulting overexpression of proximal
      microRNAs and retrotransposon-like 1 (Rtl1) were associated with HCC. In
      addition, we demonstrated that the AAV vector dose, enhancer/promoter selection,
      and the timing of gene delivery are all critical factors for determining HCC
      incidence after AAV gene delivery. Together, our results define aspects of AAV
      mediated gene therapy that influence genotoxicity and suggest that these features
      should be considered for design of both safer AAV vectors and gene therapy
      studies. 

PMID- 25607840
TI  - Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.
AB  - Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in
      turn requires anaplerosis to replenish precursor intermediates. The major
      anaplerotic sources are pyruvate and glutamine, which require the activity of
      pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their
      rapid proliferation, cancer cells have increased anabolic and energy demands;
      however, different cancer cell types exhibit differential requirements for PC-
      and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we
      infused patients with early-stage non-small-cell lung cancer (NSCLC) with
      uniformly 13C-labeled glucose before tissue resection and determined that the
      cancerous tissues in these patients had enhanced PC activity. Freshly resected
      paired lung tissue slices cultured in 13C6-glucose or 13C5,15N2-glutamine tracers
      confirmed selective activation of PC over GLS in NSCLC. Compared with
      noncancerous tissues, PC expression was greatly enhanced in cancerous tissues,
      whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis
      of paired lung tissues showed PC overexpression in cancer cells rather than in
      stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased
      cell proliferation and colony formation in human NSCLC cells, and reduced tumor
      growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed
      Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and
      altered glutathione homeostasis. These findings indicate that PC-mediated
      anaplerosis in early-stage NSCLC is required for tumor survival and
      proliferation. 

PMID- 25607841
TI  - GP96 is a GARP chaperone and controls regulatory T cell functions.
AB  - Molecular chaperones control a multitude of cellular functions via folding
      chaperone-specific client proteins. CD4+FOXP3+ Tregs play key roles in
      maintaining peripheral tolerance, which is subject to regulation by multiple
      molecular switches, including mTOR and hypoxia-inducible factor. It is not clear
      whether GP96 (also known as GRP94), which is a master TLR and integrin chaperone,
      controls Treg function. Using murine genetic models, we demonstrated that GP96 is
      required for Treg maintenance and function, as loss of GP96 resulted in
      instability of the Treg lineage and impairment of suppressive functions in vivo.
      In the absence of GP96, Tregs were unable to maintain FOXP3 expression levels,
      resulting in systemic accumulation of pathogenic IFN-gamma-producing and IL-17
      producing T cells. We determined that GP96 serves as an essential chaperone for
      the cell-surface protein glycoprotein A repetitions predominant (GARP), which is
      a docking receptor for latent membrane-associated TGF-beta (mLTGF-beta). The loss
      of both GARP and integrins on GP96-deficient Tregs prevented expression of mLTGF
      beta and resulted in inefficient production of active TGF-beta. Our work
      demonstrates that GP96 regulates multiple facets of Treg biology, thereby placing
      Treg stability and immunosuppressive functions strategically under the control of
      a major stress chaperone. 

PMID- 25607842
TI  - MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.
AB  - A body of experimental evidence suggests that T cells mediate neuroprotection
      following CNS injury; however, the antigen specificity of these T cells and how
      they mediate neuroprotection are unknown. Here, we have provided evidence that T
      cell-mediated neuroprotection after CNS injury can occur independently of major
      histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using
      two murine models of CNS injury, we determined that damage-associated molecular
      mediators that originate from injured CNS tissue induce a population of
      neuroprotective, IL-4-producing T cells in an antigen-independent fashion.
      Compared with wild-type mice, IL-4-deficient animals had decreased functional
      recovery following CNS injury; however, transfer of CD4+ T cells from wild-type
      mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a
      culture-based system, we determined that T cell-derived IL-4 protects and induces
      recovery of injured neurons by activation of neuronal IL-4 receptors, which
      potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these
      findings demonstrate that damage-associated molecules from the injured CNS induce
      a neuroprotective T cell response that is independent of MHCII/TCR interactions
      and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates
      neuroprotection and recovery of the injured CNS and suggest that strategies to
      enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in
      the course of CNS injury in trauma, inflammation, or neurodegeneration. 

PMID- 25607843
TI  - Neonatal ghrelin programs development of hypothalamic feeding circuits.
AB  - A complex neural network regulates body weight and energy balance, and
      dysfunction in the communication between the gut and this neural network is
      associated with metabolic diseases, such as obesity. The stomach-derived hormone
      ghrelin stimulates appetite through interactions with neurons in the arcuate
      nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and
      neurobiological contribution of ghrelin during development by specifically
      blocking ghrelin action during early postnatal development in mice. Ghrelin
      blockade in neonatal mice resulted in enhanced ARH neural projections and long
      term metabolic effects, including increased body weight, visceral fat, and blood
      glucose levels and decreased leptin sensitivity. In addition, chronic
      administration of ghrelin during postnatal life impaired the normal development
      of ARH projections and caused metabolic dysfunction. Consistent with these
      observations, direct exposure of postnatal ARH neuronal explants to ghrelin
      blunted axonal growth and blocked the neurotrophic effect of the adipocyte
      derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also
      attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these
      data reveal that ghrelin plays an inhibitory role in the development of
      hypothalamic neural circuits and suggest that proper expression of ghrelin during
      neonatal life is pivotal for lifelong metabolic regulation. 

PMID- 25607847
TI  - Tumor initiation by skin Ha-ras-ment.

PMID- 25607844
TI  - Disrupting SUMOylation enhances transcriptional function and ameliorates
      polyglutamine androgen receptor-mediated disease.
AB  - Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR)
      causes neuromuscular degeneration in individuals with spinobulbar muscular
      atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits
      ligand-dependent proteotoxicity, features that have both been implicated in SBMA;
      however, the extent to which altered AR transcriptional function contributes to
      pathogenesis remains controversial. Here, we sought to dissociate effects of
      diminished AR function from polyQ-mediated proteotoxicity by enhancing the
      transcriptional activity of polyQ AR. To accomplish this, we bypassed the
      inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like
      modifier) by mutating conserved lysines in the polyQ AR that are sites of
      SUMOylation. We determined that replacement of these residues by arginine
      enhances polyQ AR activity as a hormone-dependent transcriptional regulator. In a
      murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and
      type I muscle fiber atrophy; it also prolonged survival. These changes occurred
      without overt alterations in polyQ AR expression or aggregation, revealing the
      favorable trophic support exerted by the ligand-activated receptor. Our findings
      demonstrate beneficial effects of enhancing the transcriptional function of the
      ligand-activated polyQ AR and indicate that the SUMOylation pathway may be a
      potential target for therapeutic intervention in SBMA. 

PMID- 25607846
TI  - Relative sensitivity of conventional and real-time PCR assays for detection of
      SFG Rickettsia in blood and tissue samples from laboratory animals.
AB  - Studies on the natural transmission cycles of zoonotic pathogens and the
      reservoir competence of vertebrate hosts require methods for reliable diagnosis
      of infection in wild and laboratory animals. Several PCR-based applications have
      been developed for detection of infections caused by Spotted Fever group
      Rickettsia spp. in a variety of animal tissues. These assays are being widely
      used by researchers, but they differ in their sensitivity and reliability. We
      compared the sensitivity of five previously published conventional PCR assays and
      one SYBR green-based real-time PCR assay for the detection of rickettsial DNA in
      blood and tissue samples from Rickettsia- infected laboratory animals (n = 87).
      The real-time PCR, which detected rickettsial DNA in 37.9% of samples, was the
      most sensitive. The next best were the semi-nested ompA assay and rpoB
      conventional PCR, which detected as positive 18.4% and 14.9% samples
      respectively. Conventional assays targeting ompB, gltA and hrtA genes have been
      the least sensitive. Therefore, we recommend the SYBR green-based real-time PCR
      as a tool for the detection of rickettsial DNA in animal samples due to its
      higher sensitivity when compared to more traditional assays. 

PMID- 25607848
TI  - Correction: A Large Extension to HIV-1 Gag, Like Pol, Has Negative Impacts on
      Virion Assembly.

PMID- 25607849
TI  - Solvent-dependent dynamics of a series of rhenium photoactivated catalysts
      measured with ultrafast 2DIR.
AB  - The spectral dynamics of a series of rhenium photocatalysts, fac-Re(4,4'-R2
      bpy)(CO)3Cl, where R = H, methyl, t-butyl, and carboxylic acid, as well as
      Re(1,10-phenanthroline)(CO)3Cl were observed in multiple aprotic solvents using
      two-dimensional infrared spectroscopy (2DIR). The carbonyl vibrational stretching
      frequencies showed slight variations due to the electron-donating or -withdrawing
      nature of the substituents on the bipyridine. The different substituents had
      minimal to no influence on the spectral diffusion time scales of the compounds
      within a particular solvent, but among the three different solvents investigated
      (DMSO, THF, and CH3CN), we find the spectral diffusion times to correlate with
      the solvent's donor number (DN). Because the donicity is a measure the Lewis
      basicity of the solvent, these findings may help establish a more complete
      dynamical picture of the photocatalysis, where the first chemical step following
      optical excitation is electron transfer from a sacrificial donor to the rhenium
      complex. 

PMID- 25607845
TI  - CRALBP supports the mammalian retinal visual cycle and cone vision.
AB  - Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by
      RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It
      is not known how CRALBP supports cone function or how altered CRALBP leads to
      cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the
      retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M
      cone loss, and impaired cone-driven visual behavior and light responses.
      Additionally, M-cone dark adaptation was largely suppressed in CRALBP-deficient
      animals. While rearing CRALBP-deficient mice in the dark prevented the
      deterioration of cone function, it did not rescue cone dark adaptation. Adeno
      associated virus-mediated restoration of CRALBP expression specifically in Muller
      cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual
      cycle and M-cone sensitivity in knockout mice. Our results identify Muller cell
      CRALBP as a key component of the retinal visual cycle and demonstrate that this
      pathway is important for maintaining normal cone-driven vision and accelerating
      cone dark adaptation. 

PMID- 25607850
TI  - Reduced Coenzyme Q10 Decreases Urinary 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine
      Concentrations in Healthy Young Female Subjects.
AB  - It remains unclear whether dietary supplementation with coenzyme Q10 (CoQ10)
      provides beneficial effects for healthy individuals, especially young subjects.
      This study investigated the effects of dietary supplementation with CoQ10 on
      oxidative stress in healthy young females. We performed a placebo-controlled
      trial using a crossover design (n=28) with 100 mg/day CoQ10 in reduced form or
      placebo, each lasting 2 weeks with a 2-week interval. The urinary levels of 8-oxo
      7,8-dihydro-2'-deoxyguanosine (8-oxodG), a biomarker of oxidative DNA damage,
      were determined by high-performance liquid chromatography (HPLC) coupled to an
      electrochemical detector. Levels of malondialdehyde (MDA), a biomarker of lipid
      peroxidation, and antioxidant vitamin C in urine were also measured using a
      thiobarbituric acid-reactive substance method with a commercial kit and by the
      2,4-dinitrophenylhydrazine method with HPLC, respectively. Urinary 8-oxodG levels
      during supplementation with reduced form of CoQ10 (median [first and third
      quartiles]: 1.76 [1.24-2.08] nmol/mmol creatinine) were significantly lower than
      those with placebo (2.00 [1.34-2.49] nmol/mmol creatinine, P=.031 by Student's
      paired t-test using the logarithmically transformed values). In contrast, the
      urinary levels of MDA and vitamin C were not significantly affected (P=.094 and
      P=.247 by Student's paired t-test, respectively). There was no evidence of any
      side effects. Supplementation with CoQ10 in the reduced form showed a slightly
      protective effect against oxidative DNA damage even in healthy young subjects. 

PMID- 25607854
TI  - Simultaneous measurement of refractive index and temperature using an epoxy resin
      based interferometer.
AB  - A fiber-optics reflection probe based on fiber Fabry-Perot interference (FFPI) is
      proposed and experimentally demonstrated. The sensing structure comprises an
      epoxy resin (ER)-based cap on the end-face of the single-mode fiber. A well
      defined interference spectrum is obtained by the reflective beams of two surfaces
      of the ER cap. The simultaneous measurements, including fringe contrast
      referenced for the surrounding refractive index (SRI) and wavelength-referenced
      for temperature, have been achieved via selective interference dips monitoring.
      Experimental results indicate that the proposed FFPI presents an SRI sensitivity
      of 57.69 dB/RIU in the measurement range of 1.33-1.40 RIU and a temperature
      sensitivity of 0.98  pm.MUm<sup>-1</sup>. degrees C<sup>-1</sup> with per unit
      cavity length in the range of 30 degrees C-70 degrees C. The proposed sensor has
      advantages of being compact and robust, making it an alternative candidate as a
      smart sensor in chemical and biological applications. 

PMID- 25607855
TI  - Design of an ultra-short coupler in an asymmetric twin-waveguide structure using
      transformation optics.
AB  - An integrated vertical coupler that transfers light from the lower passive
      waveguide to the upper active waveguide in an asymmetric twin-waveguide
      integration structure (in InGaAsP/InP material system) is designed using
      transformation optics (TO). The length of the coupler is as short as 3 MUm, which
      is two orders of magnitude shorter than that of traditional tapered couplers.
      According to three-dimensional full-wave simulations, the designed optimized
      coupler has a high coupling efficiency of 94.9%, and a low reflection at the
      wavelength of 1.55 MUm. Subsequently, quasi-conformal mapping is employed to
      reduce the material complexity and to make it possible to realize the coupler by
      purely using an isotropic dielectric material. Applying TO to integrated photonic
      devices may motivate new applications, and improve integration density on the InP
      platform. 

PMID- 25607856
TI  - Isotropic superresolution imaging for fluorescence emission difference
      microscopy.
AB  - Fluorescence emission diffraction microscopy (FED) has proven to be an effective
      sub-diffraction-limited imaging method. In this paper, we theoretically propose a
      method to further enhance the resolving capability of FED. Using a coated mirror
      and only one objective lens, this method achieves not only the same axial
      resolution as 4Pi microscopy but also a higher lateral resolution. The point
      spread function (PSF) of our method is isotropic. According to calculations, the
      full width at half-maximum (FWHM) of the isotropic FED's PSF is 0.17lambda along
      all three spatial directions. Compared with confocal microscopy, the lateral
      resolution is improved 0.7-fold, and the axial resolution is improved 3.1-fold.
      Simulation tests also demonstrate this method's advantage over traditional
      microscopy techniques. 

PMID- 25607857
TI  - Numerical investigation on the generation of high-order Laguerre-Gaussian beams
      in end-pumped solid-state lasers by introducing loss control.
AB  - This paper reports a robust and systematic approach to generate high-order scalar
      Laguerre-Gaussian (LG<sub>p,l</sub>) beams in end-pumped solid-state lasers by
      introducing loss control. Based on the spatial distributions of Laguerre-Gaussian
      modes and the theory of transverse mode selection, the "loss control" is
      implemented by an amplitude mask in the resonator. This proposed mechanism can be
      divided into three categories: radial loss, azimuthal loss, and the combination
      of radial and azimuthal loss, which correspond to excite radial high-order modes
      (LG<sub>p,0</sub>), azimuthal high-order modes (LG<sub>0,l</sub>), and regular
      high-order modes (LG<sub>p,l</sub>), respectively. By controlling the locations
      and thicknesses of opaque rings and lines on the mask, all kinds of
      LG<sub>p,l</sub> modes can be obtained. With the application of mode purity, all
      the generated modes possess high mode purities greater than 93% in simulation. 

PMID- 25607858
TI  - Determination of point-spread function of paper substrate based on light
      scattering simulation.
AB  - The objective of this work was to establish the relationship between the
      calculated subsurface scattered-photon distribution and the mathematical quantity
      known as point-spread function (PSF). Photon distribution of subsurface scattered
      light was calculated using the Monte Carlo method developed for describing
      reflectance and opacity of paper and of images printed on paper. The obtained
      normalized photon distribution made it possible to separate optical and
      mechanical components of dot gain for the paper-ink system. In the presented
      method of obtaining the reflectance profile of a screen element, the PSF
      convolves with a modelled reflectance profile of that element. It was found that
      the PSF can be better approximated by means of the Lorentzian function when
      compared to the Gaussian profile that was used in the past research on this
      topic. 

PMID- 25607859
TI  - Quick topological method for acquiring the beacon in inter-satellite laser
      communications.
AB  - Background starlight can lead to some spot noise in the image collected by a CCD,
      disturbing the beacon acquisition in inter-satellite laser communications.
      Removing the spot noise takes much time by using the existing method that is
      based on the reference star calendar table. We present a novel method to reduce
      the processing time in this paper. The key point is to use the topological
      characteristic of the spot noise in the graph that is obtained through threshold
      segmentation to the image on the CCD. The method helps to improve the acquisition
      probability and to save valuable onboard computing resources. 

PMID- 25607860
TI  - Fabrication of high quality and low cost microlenses on a glass substrate by
      direct printing technique.
AB  - The fabrication of high quality and low cost microlenses on a glass substrate
      using a simple, rapid, and precise direct microplotting technique is shown in
      this paper. The fabrication method is based on the use of a microplotter system,
      which is significantly different from the existing inkjet, roll-to-roll printing,
      and reactive ion etching technology and could work with higher viscosity
      materials. By optimizing the parameters of voltage, dispense time, and
      concentration of the polymer solution, high quality microlenses with a diameter
      of 20 MUm could be obtained. The geometrical and optical characteristics of the
      microlenses are analyzed by measurement of the surface profile and the imaging
      properties in the near-field and far-field zones as well as the diffraction
      pattern. We think that the fabricated microlenses could be attractive for
      enhancing the light extraction efficiency of light emitting diodes. 

PMID- 25607861
TI  - Quality control of leather by terahertz time-domain spectroscopy.
AB  - We use terahertz time-domain spectroscopy, combined with effective-medium theory,
      to measure the moisture content and thickness of leather simultaneously. These
      results demonstrate that this method could become a standard quality control test
      for the industrial tanning process. 

PMID- 25607863
TI  - Extending the mode-hop-free tuning range of an external-cavity diode laser by
      synchronous tuning with mode matching.
AB  - We present an effective method to extend the mode-hop-free (MHF) tuning range of
      an external-cavity diode laser (ECDL) by synchronous tuning of the longitudinal
      modes of the external cavity and the internal cavity, with the mode also matched
      in the initial state. Both the principle of synchronous tuning and the condition
      of mode matching in a Littman-configuration ECDL are introduced. The necessary
      tuning parameters could simply be estimated by the output power curve of the
      tuning with a single photodiode. By using this tuning method, we increased the
      MHF tuning range of an ECDL with a nonoptimized reflector pivot position from
      several gigahertzes to over 78 GHz around 774.5 nm. The tuning performance of the
      ECDL could meet the requirement of frequency scanned interferometry. 

PMID- 25607864
TI  - Angle of incidence of minimum reflectance of a dielectric-conductor interface for
      incident unpolarized or circularly polarized light.
AB  - The angle of incidence phi=phi<sub>u min</sub> of minimum reflectance for
      incident unpolarized or circularly polarized light at a dielectric-conductor
      interface is determined for any complex relative refractive index N=(n,k), and
      contours of constant phi<sub>u min</sub> in the nk plane are presented. The
      minimum reflectance R<sub>u min</sub> at phi<sub>u min</sub> is also plotted as a
      function of the polar angle 0<=theta=arg(N)<=90 degrees  along each constant
      phi<sub>u min</sub> contour. Also presented are families of R<sub>u</sub>-versus
      phi curves for values of complex N at theta=30 degrees , phi<sub>u min</sub>=45
      degrees  to 85 degrees  in steps of 10 degrees , and values of complex N at
      phi<sub>u min</sub>=75 degrees , theta=0 degrees  to 90 degrees  in steps of 10
      degrees . Finally, a nonpolarimetric method for the determination of n and k of
      optical materials, which is based on measurements of phi<sub>u min</sub> and the
      normal-incidence reflectance R<sub>0</sub>, is proposed. 

PMID- 25607865
TI  - High-resolution reconstruction for terahertz imaging.
AB  - We present a high-resolution (HR) reconstruction model and algorithms for
      terahertz imaging, taking advantage of super-resolution methodology and
      algorithms. The algorithms used include projection onto a convex sets approach,
      iterative backprojection approach, Lucy-Richardson iteration, and 2D wavelet
      decomposition reconstruction. Using the first two HR reconstruction methods, we
      successfully obtain HR terahertz images with improved definition and lower noise
      from four low-resolution (LR) 22*24 terahertz images taken from our homemade THz
      TDS system at the same experimental conditions with 1.0 mm pixel. Using the last
      two HR reconstruction methods, we transform one relatively LR terahertz image to
      a HR terahertz image with decreased noise. This indicates potential application
      of HR reconstruction methods in terahertz imaging with pulsed and continuous wave
      terahertz sources. 

PMID- 25607866
TI  - Comparative study on diode-pumped continuous wave laser at 607  nm using
      differently doped Pr(3+):LiYF(4) crystals and wavelength tuning to 604  nm.
AB  - We comparatively study an InGaN laser-diode-pumped continuous-wave laser at ~607 
      nm (sigma polarization) using differently doped Pr:LiYF<sub>4</sub> single
      crystals. Maximum output power and slope efficiency at this wavelength were up to
      209 mW and 47.1%, respectively, using a 0.2 at. % doped and 8 mm sample. Findlay
      Clay analysis shows roundtrip losses, including reabsorption loss at this
      particular emission of about 1.2% using the 0.2 at. % doped sample, which is
      lower than that of samples with higher doping concentrations at 0.5 and 1 at. %.
      Using a 0.15 mm glass plate as a Fabry-Perot etalon, a maximum output power of 73
      mW was achieved at ~604  nm (pi polarization) with slope efficiency of 17.2% for
      what is believed to be the highest result currently. 

PMID- 25607867
TI  - Application of a synthetic extended source for interferometry.
AB  - This paper presents the design of a synthetic extended source (SES) that reduces
      coherent noise in interferometric measurements. The SES uses a fully coherent
      source for data acquisition to preserve high-contrast interferograms. Multiple
      measurements are made while the point source is translated according to a
      prescribed trajectory. The average of the measurements has the effect of using a
      source with a distribution defined by the trajectory. Thus, the optical system
      uses a coherent point source, but the data combination synthesizes the behavior
      of an extended source. A parametric model to quantify measurement noise due to
      diffraction from small particles is developed and used to evaluate SES designs.
      Experimental results are shown that validate the modeling. An example of a
      practical working SES implemented in a custom SPSI interferometer is provided. 

PMID- 25607868
TI  - Three-dimensional imaging based on electronically adaptive liquid crystal lens.
AB  - In this paper, we present a relatively simple method to acquire a 3D image based
      on an electrically controlled liquid crystal (LC) lens. Its advantage is that
      this proposed method does not need any mechanical movements to acquire a 3D
      image. The tunable-focus LC lens combined with a high-resistance layer (PEDOT) is
      applied by an overdrive method to become a key optical component for use in a 3D
      imaging system. Multiple 2D images of slightly different perspectives are
      recorded, respectively, and 3D images, according to a proposed mapping and
      projection method, can be reconstructed. This is the first report, to the best of
      our knowledge, on using an LC lens to reconstruct 3D images. The proposed 3D
      imaging system is novel for its compact and smart features, so it is attractive
      for some compact 3D imaging systems. 

PMID- 25607869
TI  - Separation of specular and diffuse components using tensor voting in color
      images.
AB  - Most methods for the detection and removal of specular reflections suffer from
      nonuniform highlight regions and/or nonconverged artifacts induced by
      discontinuities in the surface colors, especially when dealing with highly
      textured, multicolored images. In this paper, a novel noniterative and predefined
      constraint-free method based on tensor voting is proposed to detect and remove
      the highlight components of a single color image. The distribution of diffuse and
      specular pixels in the original image is determined using tensors' saliency
      analysis, instead of comparing color information among neighbor pixels. The
      achieved diffuse reflectance distribution is used to remove specularity
      components. The proposed method is evaluated quantitatively and qualitatively
      over a dataset of highly textured, multicolor images. The experimental results
      show that our result outperforms other state-of-the-art techniques. 

PMID- 25607870
TI  - Localization of light in the atomic medium induced by the Hermite-cosine-Gauss
      field.
AB  - This paper provides a way of realizing light wave localization via
      electromagnetically induced transparency, which is quite different from the
      traditional, off-resonant mechanism-based Aubry-Andre model. The localization of
      light in a one-dimensional atomic medium is reported in this paper. The medium
      suggested in this paper is a resonant cold atomic ensemble with N-configuration,
      which can be modulated to be a quasi-periodic structure in the center area. As
      the paraxial signal field propagates in the medium, localization can be realized.
      The localization point and the propagation properties of the signal field are
      studied in this paper. 

PMID- 25607871
TI  - Structured light system calibration method with optimal fringe angle.
AB  - For structured light system calibration, one popular approach is to treat the
      projector as an inverse camera. This is usually performed by projecting
      horizontal and vertical sequences of patterns to establish one-to-one mapping
      between camera points and projector points. However, for a well-designed system,
      either horizontal or vertical fringe images are not sensitive to depth variation
      and thus yield inaccurate mapping. As a result, the calibration accuracy is
      jeopardized if a conventional calibration method is used. To address this
      limitation, this paper proposes a novel calibration method based on optimal
      fringe angle determination. Experiments demonstrate that our calibration approach
      can increase the measurement accuracy up to 38% compared to the conventional
      calibration method with a calibration volume of 300(H)  mm*250(W)  mm*500(D)  mm.

PMID- 25607872
TI  - Mid-infrared rotated image singly resonant twisted rectangle optical parametric
      oscillator based on HgGa(2)S(4) pumped at 1064 nm.
AB  - We compare linear, planar ring, and rotated image singly resonant twisted
      rectangle (RISTRA) type nanosecond optical parametric oscillator cavities using
      HgGa<sub>2</sub>S<sub>4</sub> nonlinear crystal pumped by 8 ns pulses at 1064 nm
      from a low beam quality pump source. The input-output characteristics and the
      output idler beam quality at 6300 nm are compared for two values of the pump beam
      diameter presenting different cavity Fresnel numbers and magnitudes of the
      spatial walk-off effect due to birefringence. The RISTRA cavity ensures in all
      cases a circular output beam profile but is advantageous in terms of beam quality
      with respect to the planar ring only at a large pump beam diameter. 

PMID- 25607873
TI  - Method to improve beam quality by compensating spherical aberrations in master
      oscillator power amplifier laser systems.
AB  - A method is presented for beam quality improvement, in master oscillator power
      amplifier laser systems. Intensive study was first carried out with the beam
      wavefront evolution in a laser resonator. When the laser beam propagates inside
      the resonator, the spherical aberration coefficient of the beam wavefront can
      change sign, i.e., the negative spherical aberration coefficient can turn to
      positive, and vice versa. This process also occurs when the beam propagates
      outside the resonator in a free space. The laser beam, from an oscillator with
      negative spherical aberration, was found to be well-compensated by the positive
      spherical aberration of a strongly pumped laser rod in a laser amplifier. The
      laser beam quality M<sup>2</sup> factor has been significantly improved, from 2.2
      to 1.4, while the output power has been scaled from 31 W up to 60 W. 

PMID- 25607874
TI  - Field correlation of spherical wave in underwater turbulent medium.
AB  - The absolute field correlation of the spherical wave in an underwater turbulent
      medium is investigated at the receiver plane by using the extended Huygens
      Fresnel principle. Results denote that increase in the propagation distance, the
      rate of dissipation of the mean squared temperature, and microscale length cause
      reduction in the absolute field correlation. Field correlation increases when the
      wavelength and the rate of dissipation of the turbulent kinetic energy and
      parameters of temperature and salinity contribution to the turbulence decrease.
      Salinity dominated turbulence corrupts the absolute field correlation much more
      in comparison to the temperature dominated turbulence. Change in the receiver
      coordinate is found not to affect the absolute field correlation. 

PMID- 25607875
TI  - Truncated corner cubes with near-perfect retroreflection efficiency.
AB  - By isolating a finite effective volume from a conventional triangular pyramid
      corner cube, we obtained truncated corner cube structures with greatly enhanced
      retroreflection efficiency. We explore an optimal truncated corner cube with near
      100% retroreflection efficiency based on the expectation that the traveling paths
      of the optical rays can be localized in the finite effective volume of the
      structure, and, as a result, truncated corner cubes with perfect efficiency can
      be produced. As a case study, the retroreflection efficiency of a commercialized
      3M truncated corner cube sample is evaluated. Furthermore, it is shown with
      numerical verification that a truncated corner cube array sheet with near-perfect
      retroreflection efficiency can be produced. 

PMID- 25607876
TI  - Common-pull, multiple-push, vacuum-activated telescope mirror cell.
AB  - A new concept for push-pull active optics is presented, where the push-force is
      provided by means of individual airbag type actuators and a common force in the
      form of a vacuum is applied to the entire back of the mirror. The vacuum provides
      the pull-component of the system, in addition to gravity. Vacuum is controlled as
      a function of the zenithal angle, providing correction for the axial component of
      the mirror's weight. In this way, the push actuators are only responsible for
      correcting mirror deformations, as well as for supporting the axial mirror weight
      at the zenith, allowing for a uniform, full dynamic-range behavior of the system
      along the telescope's pointing range. This can result in the ability to perform
      corrections of up to a few microns for low-order aberrations. This mirror support
      concept was simulated using a finite element model and was tested experimentally
      at the 2.12 m San Pedro Martir telescope. Advantages such as stress-free
      attachments, lighter weight, large actuator area, lower system complexity, and
      lower required mirror-cell stiffness could make this a method to consider for
      future large telescopes. 

PMID- 25607877
TI  - Pulsed photothermal mirror technique: characterization of opaque materials.
AB  - The time-resolved thermal mirror technique is developed under pulsed laser
      excitation for quantitative measurement of thermal and mechanical properties of
      opaque materials. Heat diffusion and thermoelastic equations are solved
      analytically for pulsed excitation assuming surface absorption and an
      instantaneous pulse. Analytical results for the temperature change and surface
      displacement in the sample are compared to all-numerical solutions using finite
      element method analysis accounting for the laser pulse width and sample geometry.
      Experiments are performed that validate the theoretical model and regression
      fitting is performed to obtain the thermal diffusivity and the linear thermal
      expansion coefficient of the samples. The values obtained for these properties
      are in agreement with literature data. The technique is shown to be useful for
      quantitative determinations of the physics properties of metals with high thermal
      diffusivity. 

PMID- 25607878
TI  - Three-dimensional imaging reconstruction algorithm of gated-viewing laser imaging
      with compressive sensing.
AB  - Three-dimensional (3D) laser imaging combining compressive sensing (CS) has an
      advantage in lower power consumption and less imaging sensors; however, it brings
      enormous stress to subsequent calculation devices. In this paper we proposed a
      fast 3D imaging reconstruction algorithm to deal with time-slice images sampled
      by single-pixel detectors. The algorithm implements 3D imaging reconstruction
      before CS recovery, thus it saves plenty of runtime of CS recovery. Several
      experiments are conducted to verify the performance of the algorithm. Simulation
      results demonstrated that the proposed algorithm has better performance in terms
      of efficiency compared to an existing algorithm. 

PMID- 25607879
TI  - Sellmeier and thermo-optic dispersion formulas for LiInS(2).
AB  - This paper reports on improved Sellmeier and thermo-optic dispersion formulas for
      LiInS<sub>2</sub>, which provide an excellent reproduction of the temperature
      dependent phase-matching conditions for second, sum-, and difference-frequency
      generation achieved in the 1.0642-10.5910 MUm range. 

PMID- 25607880
TI  - Shaping of steel mold surface of lens array by electrical discharge machining
      with single rod electrode.
AB  - We propose a method for fabricating a lens array mold by electrical discharge
      machining (EDM). In this method, the tips of rods are machined individually to
      form a specific surface, and then a number of the machined rods are arranged to
      construct an electrode for EDM. The repetition of the EDM process using the
      electrode enables a number of lens elements to be produced on the mold surface.
      The effectiveness of our proposed method is demonstrated by shaping a lens array
      mold made of stainless steel with 16 spherical elements, in which the EDM process
      with a single rod electrode is repeatedly conducted. 

PMID- 25607883
TI  - Inside the structure of a nanocomposite electrolyte membrane: how hybrid
      particles get along with the polymer matrix.
AB  - Hybrid materials remain the target for a fruitful range of investigations,
      especially for energy devices. A number of hybrid electrolyte membranes
      consisting of inorganic and organic phases were then synthesized. Mechanical,
      solvent uptake and ionic transport properties were studied with the key point
      being the characteristic length scale of the interaction between the phases. A
      group of nanocomposite membranes made of polystyrenesulfonic acid-grafted silica
      particles embedded in a Poly(Vinylidene Fluoride-co-HexaFluoroPropene) (PVdF-HFP)
      matrix was studied by combining neutron and X-ray scatterings on the nanometer to
      angstrom scale. This approach allows for the variation in the morphology and
      structure as a function of particle loading to be described. These studies showed
      that the particles aggregate with increasing particle loading and these
      aggregates swell, creating a physical interaction with the polymer matrix.
      Particle loadings lower than 30 wt% induce a slight strain between both of the
      subphases, namely the polymer matrix and the particles. This strain is decreased
      with particle loading between 20 and 30 wt% conjointly with the beginning of
      proton conduction. Then the percolation of the aggregates is the beginning of a
      significant increase of the conduction without any strain. This new insight can
      give information on the variation in other important intrinsic properties. 

PMID- 25607881
TI  - Fascin1-dependent Filopodia are required for directional migration of a subset of
      neural crest cells.
AB  - Directional migration of neural crest (NC) cells is essential for patterning the
      vertebrate embryo, including the craniofacial skeleton. Extensive filopodial
      protrusions in NC cells are thought to sense chemo-attractive/repulsive signals
      that provide directionality. To test this hypothesis, we generated null mutations
      in zebrafish fascin1a (fscn1a), which encodes an actin-bundling protein required
      for filopodia formation. Homozygous fscn1a zygotic null mutants have normal NC
      filopodia due to unexpected stability of maternal Fscn1a protein throughout NC
      development and into juvenile stages. In contrast, maternal/zygotic fscn1a null
      mutant embryos (fscn1a MZ) have severe loss of NC filopodia. However, only a
      subset of NC streams display migration defects, associated with selective loss of
      craniofacial elements and peripheral neurons. We also show that fscn1a-dependent
      NC migration functions through cxcr4a/cxcl12b chemokine signaling to ensure the
      fidelity of directional cell migration. These data show that fscn1a-dependent
      filopodia are required in a subset of NC cells to promote cell migration and NC
      derivative formation, and that perdurance of long-lived maternal proteins can
      mask essential zygotic gene functions during NC development. 

PMID- 25607882
TI  - New insights into structure and luminescence of Eu(III) and Sm(III) complexes of
      the 3,4,3-LI(1,2-HOPO) ligand.
AB  - We report the preparation and new insight into photophysical properties of
      luminescent hydroxypyridonate complexes [M(III)L](-) (M = Eu or Sm) of the
      versatile 3,4,3-LI(1,2-HOPO) ligand (L). We report the crystal structure of this
      ligand with Eu(III) as well as insights into the coordination behavior and
      geometry in solution by using magnetic circular dichroism. In addition TD-DFT
      calculations were used to examine the excited states of the two different
      chromophores present in the 3,4,3-LI(1,2-HOPO) ligand. We find that the Eu(III)
      and Sm(III) complexes of this ligand undergo a transformation after in situ
      preparation to yield complexes with higher quantum yield (QY) over time. It is
      proposed that the lower QY in the in situ complexes is not only due to water
      quenching but could also be due to a lower degree of f-orbital overlap (in a
      kinetic isomer) as indicated by magnetic circular dichroism measurements. 

PMID- 25607884
TI  - Cross-protection against influenza virus infection by intranasal administration
      of nucleoprotein-based vaccine with compound 48/80 adjuvant.
AB  - The nucleoprotein (NP) of influenza viruses is highly conserved and therefore has
      become one of the major targets of current universal influenza vaccine (UIV)
      studies. In this study, the recombinant nucleoprotein (NP) of the A/PR/8/34
      (H1N1) influenza virus strain was expressed using an Escherichia coli (E. coli)
      expression system and then purified as a candidate UIV. The NP protein was
      administered intranasally or intraperitoneally twice at 3-week intervals to
      female BALB/c mice in combination with C48/80 adjuvant. Then, the mice were
      challenged with homologous or heterologous influenza viruses at a lethal dose 3
      weeks after the last immunization. The results showed that the serum IgG titers
      of all of the mice immunized with NP reached a higher level and the protection
      provided by NP vaccine against the homologous virus depended on the administered
      dosage and adjuvant. In addition, immunization with 100 MUg NP in combination
      with C48/80 adjuvant could provide good cross-protection against heterologous
      H9N2 avian influenza viruses. This study indicated that NP as a candidate antigen
      of UIV immunized intranasally could effectively induce mucosal and cell-mediated
      immunity, with the potential to control epidemics caused by the appearance of new
      emerging influenza viruses. 

PMID- 25607886
TI  - Reversal of diastereoselectivity in the synthesis of peptidomimetic 3-carboxamide
      1,4-benzodiazepin-5-ones.
AB  - Enantiopure 3-carboxamide-1,4-benzodiazepin-5-ones were synthesized via the Ugi
      reaction followed by the Staudinger/aza-Wittig or reduction reactions in only two
      steps. A complete reversal of diastereoselectivity was achieved depending on the
      cyclization methodology employed. The different orientation of the C3 substituent
      in our 3-substituted 1,4-benzodiazepin-5-ones with respect to the most studied
      1,4-benzodiazepin-2-ones makes them complementary in the development of new drugs
      because the primary source of binding selectivity of 1,4-benzodiazepines is the
      selective recognition of ligand conformations by the receptor. 

PMID- 25607885
TI  - IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity
      during T-cell-mediated colitis.
AB  - Polymorphisms attenuating IL-10 signalling confer genetic risk for inflammatory
      bowel disease. Yet, how IL-10 prevents mucosal autoinflammation is incompletely
      understood. We demonstrate using lineage-specific deletions of IL-10Ralpha that
      IL-10 acts primarily through macrophages to limit colitis. Colitis depends on IL
      6 to support pathologic Th17 cell generation in wild-type mice. However, specific
      ablation of macrophage IL-10Ralpha provokes excessive IL-1beta production that
      overrides Th17 IL-6 dependency, amplifying the colonic Th17 response and disease
      severity. IL-10 not only inhibits pro-IL-1beta production transcriptionally in
      macrophages, but suppresses caspase-1 activation and caspase-1-dependent
      maturation of pro-IL-1beta to IL-1beta. Therefore, lineage-specific effects of IL
      10 skew the cytokine dependency of Th17 cell development required for colitis
      pathogenesis. Coordinated interventions may be needed to fully suppress Th17
      mediated immunopathology. 

PMID- 25607887
TI  - Sub-50-nm self-assembled nanotextures for enhanced broadband antireflection in
      silicon solar cells.
AB  - Materials providing broadband light antireflection have applications as highly
      transparent window coatings, military camouflage, and coatings for efficiently
      coupling light into solar cells and out of light-emitting diodes. In this work,
      densely packed silicon nanotextures with feature sizes smaller than 50 nm enhance
      the broadband antireflection compared with that predicted by their geometry
      alone. A significant fraction of the nanotexture volume comprises a surface layer
      whose optical properties differ substantially from those of the bulk, providing
      the key to improved performance. The nanotexture reflectivity is quantitatively
      well-modelled after accounting for both its profile and changes in refractive
      index at the surface. We employ block copolymer self-assembly for precise and
      tunable nanotexture design in the range of ~10-70 nm across macroscopic solar
      cell areas. Implementing this efficient antireflection approach in crystalline
      silicon solar cells significantly betters the performance gain compared with an
      optimized, planar antireflection coating. 

PMID- 25607888
TI  - Chaos, change, and disruption in higher education: are we ready to respond?

PMID- 25607890
TI  - Virtual excursion to the legislature.

PMID- 25607891
TI  - Thoughts about the baby and the bathwater.

PMID- 25607892
TI  - Differential gene expression patterns in developing sexually dimorphic rat brain
      regions exposed to antiandrogenic, estrogenic, or complex endocrine disruptor
      mixtures: glutamatergic synapses as target.
AB  - The study addressed the question whether gene expression patterns induced by
      different mixtures of endocrine disrupting chemicals (EDCs) administered in a
      higher dose range, corresponding to 450*, 200*, and 100* high-end human exposure
      levels, could be characterized in developing brain with respect to endocrine
      activity of mixture components, and which developmental processes were
      preferentially targeted. Three EDC mixtures, A-Mix (anti-androgenic mixture) with
      8 antiandrogenic chemicals (di-n-butylphthalate, diethylhexylphthalate,
      vinclozolin, prochloraz, procymidone, linuron, epoxiconazole, and DDE), E-Mix
      (estrogenic mixture) with 4 estrogenic chemicals (bisphenol A, 4
      methylbenzylidene camphor, 2-ethylhexyl 4-methoxycinnamate, and butylparaben), a
      complex mixture, AEP-Mix, containing the components of A-Mix and E-Mix plus
      paracetamol, and paracetamol alone, were administered by oral gavage to rat dams
      from gestation day 7 until weaning. General developmental endpoints were not
      affected by EDC mixtures or paracetamol. Gene expression was analyzed on
      postnatal day 6, during sexual brain differentiation, by exon microarray in
      medial preoptic area in the high-dose group, and by real-time RT-PCR in medial
      preoptic area and ventromedial hypothalamus in all dose groups. Expression
      patterns were mixture, sex, and region specific. Effects of the analgesic drug
      paracetamol, which exhibits antiandrogenic activity in peripheral systems,
      differed from those of A-Mix. All mixtures had a strong, mixture-specific impact
      on genes encoding for components of excitatory glutamatergic synapses and genes
      controlling migration and pathfinding of glutamatergic and GABAergic neurons, as
      well as genes linked with increased risk of autism spectrum disorders. Because
      development of glutamatergic synapses is regulated by sex steroids also in
      hippocampus, this may represent a general target of ECD mixtures. 

PMID- 25607893
TI  - Receptor expression modulates calcium-sensing receptor mediated intracellular
      Ca2+ mobilization.
AB  - Calcium-sensing receptors (CaSRs) are class C G protein-coupled receptors that
      respond to physiological activators, including extracellular Ca2+ (Cao2+) and L
      amino acids as well as the pharmaceutical calcimimetic, cinacalcet. Unlike Cao2+,
      which is an orthosteric agonist, L-amino acids and cinacalcet are positive
      allosteric modulators. CaSR expression levels vary considerably between tissues,
      but the physiological significance of these differences in expression for the
      effects of its activators is unknown. To investigate the impact of receptor
      expression on CaSR-mediated signaling we used a tetracycline-inducible expression
      system and focused on intracellular Ca2+ (Cai2+) responses in single cells and
      considered both population and single-cell behavior. Increased receptor
      expression positively modulated CaSR-mediated Cai2+ mobilization in response to
      elevated Cao2+, the amino acid L-phenylalanine, or the calcimimetic cinacalcet.
      It lowered threshold concentrations for the initiation of Cai2+ oscillations and
      for their transformation to sustained Cai2+ elevations, and it increased the
      proportions of responding cells. It also positively modulated the frequency of
      Cai2+ oscillations with the order of effectiveness: cinacalcet equal to or
      greater than Cao2+ greater than L-phenylalanine. The results indicate that
      receptor expression modulates key characteristics of the Cai2+ response at the
      single-cell level as well as the amplitude of whole-tissue CaSR-mediated
      responses by recruiting quiescent cells into the active pool of responding cells.
      By lowering the threshold concentrations for Cao2+- and L-amino acid-induced
      responses below the physiological levels of these nutrients in plasma, mechanisms
      that up-regulate receptor expression can control tissue function in the absence
      of dynamic changes in ligand concentration.

PMID- 25607894
TI  - Sim1 inhibits bone formation by enhancing the sympathetic tone in male mice.
AB  - Single-minded 1 (Sim1) is a basic helix-loop-helix Per-Arnt-Sim transcription
      factor that is important for neuronal development in the hypothalamus. Loss-of
      function mutation of Sim1 causes early-onset obesity. However, it is unknown
      whether and how Sim1 regulates bone remodeling. In this study, we found that
      adult-onset Sim1 deletion increases bone formation, leading to high bone mass. In
      contrast, Sim1-overexpressing transgenic mice exhibit decreased bone formation
      and low bone mass. Sim1 does not directly regulate osteoblastogenesis, because
      bone marrow mesenchymal stem cells from Sim1 mutant mice display a normal
      capacity for osteoblast differentiation. Instead, Sim1 inhibits bone formation
      via stimulating the sympathetic nervous system, because sympathetic tone is
      decreased by Sim1 deletion but increased by Sim1 overexpression. Treatment with
      the beta-adrenergic agonist isoproterenol effectively reverses the high bone mass
      in Sim1-knockout mice. These findings reveal Sim1 as a critical yet previously
      unrecognized modulator of skeletal homeostasis that functions through a central
      relay. 

PMID- 25607895
TI  - Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced
      lipolysis, and protection against high-fat diet-induced obesity.
AB  - Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4)
      is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which
      governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane
      proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and
      reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles
      of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using
      a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are
      moderately insulin resistant but paradoxically protected against HFDIO. After
      high-fat diet feeding, Nedd4+/- mice showed less body weight gain, less fat mass,
      and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice
      did not manifest improvement in glucose tolerance vs the wild type in both
      genders. Nedd4+/- male, but not female, mice displayed significantly lower
      fasting blood glucose levels and serum insulin levels. Under obesogenic
      conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity,
      primarily through a beta2-adrenergic receptor. Combined, these data support novel
      complex roles for Nedd4 in metabolic regulation involving altered insulin and
      beta-adrenergic signaling pathways.

PMID- 25607897
TI  - JLAST--celebrating 25 years.

PMID- 25607898
TI  - 25(th) Anniversary state-of-the-art expert discussion with Santiago Horgan, MD,
      on robotics.

PMID- 25607896
TI  - The 40-residue insertion in Vibrio cholerae FadR facilitates binding of an
      additional fatty acyl-CoA ligand.
AB  - FadR is a master regulator of fatty acid metabolism and influences virulence in
      certain members of Vibrionaceae. Among FadR homologues of the GntR family, the
      Vibrionaceae protein is unusual in that it contains a C-terminal 40-residue
      insertion. Here we report the structure of Vibrio cholerae FadR (VcFadR) alone,
      bound to DNA, and in the presence of a ligand, oleoyl-CoA. Whereas Escherichia
      coli FadR (EcFadR) contains only one acyl-CoA-binding site in each monomer,
      crystallographic and calorimetric data indicate that VcFadR has two. One of the
      binding sites resembles that of EcFadR, whereas the other, comprised residues
      from the insertion, has not previously been observed. Upon ligand binding, VcFadR
      undergoes a dramatic conformational change that would more fully disrupt DNA
      binding than EcFadR. These findings suggest that the ability to bind and respond
      to an additional ligand allows FadR from Vibrionaceae to function as a more
      efficient regulator. 

PMID- 25607899
TI  - Appraisal of face and content validity of a serious game improving situational
      awareness in surgical training.
AB  - BACKGROUND: Equipment-related malfunctions during minimally invasive surgery
      (MIS) are common and threaten patient safety. As they occur in the periphery of
      the surgeon's vision, the surgical team requires a high level of situational
      awareness in order to intercept these errors timely. A serious game has been
      developed to train surgical residents to deal with equipment-related errors. This
      study investigates to what extent surgical educators and trainees would accept a
      serious game as a training method. MATERIALS AND METHODS: A cross-sectional
      survey was conducted among 45 surgeons, surgical residents, and medical students
      who played the serious game at a scientific convention. The questionnaire
      contained statements on perceived realism, usefulness, teaching capability, user
      experience and application toward surgical training. RESULTS were analyzed
      according to participants' MIS experience ("expert," "intermediate," and
      "novice"). RESULTS: The majority found that important medical constructs are
      represented realistically (64.4%-88.9%) and indicated the game to be particularly
      useful for training operating room nurses and surgical residents (75%-86%). Both
      educators and trainees found the game to be useful for surgical training (53%).
      Serious gaming was viewed as positive (78%) and challenging (60%), and 66% would
      play the game in their leisure time. Licensed surgeons perceived the game more
      frequently as boring than the intermediate-level and trainee groups (23.5% versus
      6.7% and 8.3%; P=.045). CONCLUSIONS: This is the first study to show acceptance
      of a serious game as a training format in surgical training by educators and
      trainees. Future research should investigate whether the serious game indeed
      improves problem-solving and situational awareness in the operating room.

PMID- 25607900
TI  - Psychosocial challenges and strategies for coping with HIV among adolescents in
      Uganda: a qualitative study.
AB  - Although more than 90% of youth perinatally infected with HIV live in sub-Saharan
      Africa, little is known about the psychosocial factors that impact their
      wellbeing, or how these youth cope with these challenges. The purpose of this
      study was to identify the psychosocial challenges and coping strategies among
      perinatal HIV-infected adolescents in Uganda. In-depth interviews were conducted
      with a purposive sample of 38 HIV-infected adolescents aged 12-19 years at a
      large HIV treatment center in Kampala. Data were analyzed thematically to
      identify themes and domains related to stressors and specific coping strategies.
      Psychosocial challenges included stigma/discrimination, relationship challenges
      such as HIV status disclosure, and medication difficulties. Coping strategies
      included medication adherence, concealment or limited disclosure of HIV status,
      treatment optimism, social support, rationalizing, social comparison,
      spirituality/religiosity, avoidance, and distraction. Age and gender differences
      also emerged: younger participants generally lacked specific coping strategies;
      compared to females, male adolescents reported greater use of
      avoidance/distraction techniques. Findings underscore the need to address stigma
      within homes and schools, and to equip adolescents with the comprehensive
      knowledge and skills to address their varied challenges. 

PMID- 25607902
TI  - Therapeutic update on the treatment of striae distensae.

PMID- 25607903
TI  - Single blind, randomized, controlled trial of a lightening product with and
      without iontophoresis versus tretinoin and vehicle for hyperpigmentation.
AB  - BACKGROUND: Hyperpigmentation is a common concern and has many causes including
      lentigines and melasma. Currently available topical products for
      hyperpigmentation are limited by their potential for irritation, lack of
      demonstrated efficacy or regulatory concerns. OBJECTIVE: To compare the efficacy
      of a new skin lightening product with and without iontophoresis to a known
      effective product (tretinoin) and placebo on hyperpigmentation caused by
      lentigines and/or melasma. Secondary objectives included an assessment of the
      product's effects on the appearance of rhytides and roughness. METHODS AND
      MATERIALS: Eighty subjects were randomized into one of four treatment groups:
      proprietary lightening product, proprietary lightening product with
      iontophoresis, tretinoin 0.05% cream, or vehicle control. Seventy-four subjects
      completed all study visits. Blinded assessments of subjects were performed at
      each visit under ambient and Wood's light. RESULTS: The proprietary skin
      lightening product improved facial hyperpigmentation versus placebo under ambient
      light (P= 0.05) and Wood's lamp (P= 0.01) examination. Tretinoin also improved
      facial hyperpigmentation versus placebo under Wood's lamp (P= 0.01). The
      proprietary product was better tolerated than tretinoin, with fewer subject
      reported side effects. CONCLUSION: The investigational product was effective and
      may be better tolerated than tretinoin cream.

PMID- 25607904
TI  - Clinical evaluation of a cross-linked hyaluronic Acid dermal filler applied for
      facial augmentation.
AB  - BACKGROUND: Hyaluronic Acid (HA) fillers are widely used for restoring facial
      volume. OBJECTIVE: A 24-week study evaluated clinical efficacy with HA. METHODS
      AND MATERIALS: Included were 15 healthy subjects recruited from 4 centers,
      between ages of 35 to 65 years, who had a Wrinkle Severity Rating Scale (WSRS)
      score >= 3, indicating moderate volume loss. Revanesse(r) Ultra (Prollenium), a
      HA dermal filler, was used. Primary study outcome was physicians scored facial
      volume correction, using the Global Aesthetic Improvement Scale (GAIS), comparing
      baseline (day 0) versus 24 weeks (end) and blindly assessed photographs. Subject
      satisfaction and comfort was evaluated using self-administered questionnaires at
      day 0 and at week 24. RESULTS: N = 15, 13 female and 2 males with a mean age
      (years) of 48.52 ( SD +/- 10.46) received treatment with HA and completed the 24
      week study. At screening they had a moderate (mean 2.85, SD +/- 0.45) WSRS score.
      At week 24 a market facial volume restoration was shown and no adverse events
      were reported. All patients reported to be satisfied with the obtained results.
      CONCLUSION: Good - excellent volume enhancement was noted almost immediately
      after the HA injections, improving patient reported quality of life aspects. HA
      treatment was shown to be safe.

PMID- 25607905
TI  - A randomized, double-blind, split-face study comparing the efficacy and
      tolerability of three retinol-based products vs. three tretinoin-based products
      in subjects with moderate to severe facial photodamage.
AB  - Retinol, has been shown to improve the appearance of photodamaged skin when
      applied topically, and is generally considered to be approximately ten times less
      potent than tretinoin. To assess this theory, three cosmetic formulations
      containing 0.25%, 0.5%, and 1.0% retinol were developed to correspond to the
      three commonly prescribed concentrations of tretinoin (0.025%, 0.05%, and 0.1%).
      A randomized, double-blind, split-face comparison study was conducted to compare
      the three concentrations retinol (Ret) including 0.25%, 0.5%, and 1.0%, against
      the respective three strengths of tretinoin (Tret) 0.025%, 0.05%, and 0.1% in
      subjects with moderate to severe facial photodamage. Subjects were randomized
      into three groups: Group 1 (Ret 0.25% vs. Tret 0.025%); Group 2 (Ret 0.5% vs.
      Tret 0.05%); and Group 3 (Ret 1.0% vs. Tret 0.1%). Within each group, subjects
      were randomized to apply Ret on one half of the face (left or right) and Tret on
      the other facial side, for a duration of twelve weeks. Clinical evaluations for
      efficacy and tolerability, as well as standardized digital photographs were
      conducted at baseline and at weeks 4, 8, and 12. Sixty-five subjects completed
      the twelve-week study (Group 1: n=24, Group 2: n=20, and Group 3: n=21). At week
      12 in all treatment groups, both Ret and Tret produced statistically significant
      improvements from baseline in all efficacy parameters, including overall
      photodamage, fine lines/wrinkles, coarse lines/wrinkles, skin tone brightness,
      mottled pigmentation, and tactile roughness (all P<0.001). There were no
      significant differences in efficacy between Ret and Tret in these efficacy
      parameters. Results from this comparison study suggest that this sustained
      release retinol complex containing multiple agents for optimal irritation control
      provides comparable improvements to tretinoin in the appearance of photodamage.

PMID- 25607906
TI  - Optimizing the use of topical brimonidine in rosacea management: panel
      recommendations.
AB  - Rosacea is a chronic inflammatory disease with a complex pathophysiology that
      manifests with central facial redness with or without papulopustular lesions.
      Often, patients with rosacea present with a constellation of signs and symptoms;
      for best results, the treatment plan should take into account all symptoms
      manifesting in the individual patient. The first available pharmacologic
      treatment to address the redness associated with rosacea is topical brimonidine.
      In the United States, brimonidine topical gel 0.33% is indicated for persistent
      facial erythema of rosacea; approval was based on clinically significant efficacy
      and good safety data from large-scale clinical trials. Use of brimonidine in
      routine clinical practice has yielded new insights that elaborate on the findings
      from clinical trials. For example, real-world use has shown that a percentage of
      patients (in our experience, approximately 10 to 20%) treated with brimonidine
      experience a worsening of erythema that has been called "rebound." Our routine
      use of this agent for >1 year has yielded strategies to set patient expectations,
      optimize treatment initiation, and minimize potential problems; this article
      details those strategies. Because we believe that the term "rebound" has been
      used to describe several physiologically distinct events, we have also proposed
      more specific terminology for such events.

PMID- 25607907
TI  - Anti-inflammatory activities of colloidal oatmeal (Avena sativa) contribute to
      the effectiveness of oats in treatment of itch associated with dry, irritated
      skin.
AB  - BACKGROUND: Oat (Avena sativa) in colloidal form is a centuries-old topical
      treatment for a variety of skin conditions, including skin rashes, erythema,
      burns, itch, and eczema; however, few studies have investigated the exact
      mechanism of action for the anti-inflammatory activity of colloidal oatmeal.
      METHODS: Four extracts of colloidal oatmeal were made with various solvents and
      tested in anti-inflammatory and antioxidant assays. In addition, an investigator
      blind study was performed with twenty-nine healthy female subjects who exhibited
      bilateral mild to moderate itch with moderate to severe dry skin on their lower
      legs. Subjects were treated with a colloidal oatmeal skin protectant lotion.
      RESULTS: Extracts of colloidal oatmeal diminished pro-inflammatory cytokines in
      vitro and the colloidal oat skin protectant lotion showed significant clinical
      improvements in skin dryness, scaling, roughness, and itch intensity.
      CONCLUSIONS: These results demonstrate that colloidal oat extracts exhibit direct
      anti-oxidant and anti-inflammatory activities, which may provide the mechanisms
      for observed dermatological benefits while using the colloidal oatmeal skin
      protectant lotion.

PMID- 25607908
TI  - Biological properties of a new volumizing hyaluronic acid filler: a systematic
      review.
AB  - BACKGROUND: Hyaluronic acid (HA) dermal fillers are effective and safe for
      correction of facial rhytides. A new volumizing HA filler, 20 mg/ml HA dermal
      filler (Juvederm(r) Voluma(r), Allergan Inc., Irvine, CA), is the only HA filler
      with a FDA indication for facial volumization due to age-related facial volume
      loss. OBJECTIVE: Evaluate the biological properties, including biochemical,
      biophysical and rheological, of this new 20 mg/ml HA dermal filler and discuss
      the importance of these properties in clinical applications. METHODS AND
      MATERIALS: A systematic search of the computerized bibliographic databases
      Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation
      Abstracts with key term "Voluma." Four articles on the biological properties of
      this new 20 mg/ ml HA dermal filler were suitable for inclusion in this review.
      RESULTS: Biological analysis of elasticity and viscosity values of this new 20
      mg/ml HA dermal filler demonstrated intermediate properties in three studies and
      high in one study compared to other HA dermal fillers. This 20 mg/ml HA dermal
      filler retained the highest elasticity and viscosity values at temperature of 37
      degrees C. Histology demonstrated that this 20 mg/ml HA dermal filler has an
      intermediate pattern of distribution within the superficial and deep reticular
      dermis. CONCLUSION: This 20 mg/ml HA dermal filler demonstrated volumizing
      ability, and maintaining viscosity and free-flowing characteristics for easy
      injection, tissue lifting, and molding. We hope future research incorporates
      biological properties analysis of this HA dermal filler in clinical trials.

PMID- 25607909
TI  - Efinaconazole topical solution, 10%: the benefits of treating onychomycosis
      early.
AB  - OBJECTIVE: To evaluate efficacy of efinaconazole topical solution, 10% in
      onychomycosis patients with early and long-standing disease. METHODS: An analysis
      of 1655 patients, aged 18-70 years, randomized to receive efinaconazole topical
      solution, 10% or vehicle from two identical multicenter, double-blind, vehicle
      controlled 48-week studies evaluating safety and efficacy. The primary end point
      was complete cure rate (0% clinical involvement of target toenail, and both
      negative potassium hydroxide examination and fungal culture) at Week 52. Three
      groups were compared: those with early disease (<1year), patients with a baseline
      disease of 1-5 years, and those with long-standing onychomycosis (>5years).
      RESULTS: The majority of patients had long-standing disease; were older, male and
      white. While nail involvement of the target toenail did not differ noticeably
      amongst the three groups, the number of nails involved did increase progressively
      with disease duration. Differences were seen in terms of infecting pathogens in
      early disease that might have important treatment implications. Efinaconazole was
      more effective in treating early disease, however more than 40% of patients with
      long-standing disease were considered treatment successes. LIMITATIONS: A period
      of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis.
      CONCLUSIONS: Treatment of onychomycosis early to avoid disease progression to
      other toenails is important. Once daily efinaconazole topical solution, 10% is
      particularly effective in these patients.

PMID- 25607910
TI  - Successful botulinum toxin (onabotulinumtoxinA) treatment of Hailey-Hailey
      disease.
AB  - Hailey-Hailey disease is a genetic disorder that affects flexural skin with
      scale, blisters, and maceration. Botulinum toxins have been previously used to
      treat Hailey-Hailey disease. Here, we present a patient who underwent one
      treatment of onabotulinumtoxinA and achieved excellent improvement that was
      sustained for three months post initial treatment.

PMID- 25607911
TI  - Effective treatment of acne scars using pneumatic injection of hyaluronic acid.
AB  - Acne scars remain a challenging condition to treat despite multiple currently
      available technologies. This study evaluated the clinical efficacy and safety of
      pneumatic injections of Hyaluronic Acid in the treatment of acne scars. Two
      patients (Fitzpatrick skin type IV-V) with acne scars received two sessions of
      pneumatic, needleless injections of crosslinked hyaluronic acid (HA) at 4-week
      intervals. The treatment response was assessed by comparing pre- and 3-month
      posttreatment clinical photography. The patients' acne scar grade improved from 2
      to 1 in the first case, and 3 to 2 in the second case, based on independent
      physician assessment. Patient degree of satisfaction was similar to the
      physicians' assessment. No significant adverse events were noted. We conclude
      that pneumatic injection technology to deliver HA to the tissue is an effective
      and safe method for improving acne scars, even in patients with dark complexion.

PMID- 25607912
TI  - Non-tuberculous mycobacterial infections following cosmetic laser procedures: a
      case report and review of the literature.
AB  - Skin infections are not uncommon after cosmetic laser procedures. Infection rates
      following ablative laser resurfacing procedures are reported to be as high as
      7.6%, compared to 1.9% for fractional ablation. An infrequent yet important
      infectious complication of ablative laser treatment is that caused by non
      tuberculous mycobacteria (NTM).

PMID- 25607913
TI  - Demonstration of the biphasic release of 0.1% halcinonide cream.
AB  - Halcinonide in Halog Cream is formulated in a unique cream base that allows a
      biphasic release of this Class II steroid. Halcinonide in this product exists in
      two phases--a solution phase that is released immediately and a suspension phase
      that has a delayed release over time. The goal of this study was to evaluate this
      biphasic release of halcinonide into the skin using a novel noninvasive method. A
      dermal tape stripping protocol was used to quantify halcinonide concentration at
      6 sequential depths in the skin of 4 sites on the forearms of 5 subjects. D
      Squame strips were sequentially applied with consistent pressure and removed at
      1, 3, 6, and 9 hours after application of halcinonide. Halcinonide was extracted
      from the strips and quantified using liquid chromatography mass spectrometry. The
      highest concentration of halcinonide was detected in strip 1 from the superficial
      stratum corneum with subsequent reduction in deeper stratum corneum layers as
      expected. The concentration increased beyond the first hour after application and
      demonstrated a sustained release into hour 6 before beginning declining.
      Similarly, the average concentration of halcinonide in strips 1 to 6 peaked at
      hour 1 and remained elevated for 6 hours. Data collected from the tape strips
      demonstrated a biphasic release of halcinonide--immediate release within 1 hour
      of application from the solution phase and continued, sustained release from the
      suspension phase following the first hour of application.

PMID- 25607917
TI  - Carbon nanotube network embroidered graphene films for monolithic all-carbon
      electronics.
AB  - A unique cage growth of graphene is developed by using carbon nanotube (CNT)
      spider webs as porous templates, resulting in CNT/graphene hybrids with high
      conductivity and mechanical flexibility. Furthermore, monolithic all-carbon
      transistors with graphene as active elements and CNT/graphene hybrids as contacts
      and interconnects are directly formed by chemical synthesis, and flexible all
      carbon bioelectronics are subsequently demonstrated for in vivo mapping of
      cardiac signals. 

PMID- 25607919
TI  - Significant enhancement of infrared photodetector sensitivity using a
      semiconducting single-walled carbon nanotube/C60 phototransistor.
AB  - A highly sensitive single-walled carbon nanotube/C60 -based infrared photo
      transistor is fabricated with a responsivity of 97.5 A W(-1) and detectivity of
      1.17 * 10(9) Jones at 1 kHz under a source/drain bias of -0.5 V. The much
      improved performance is enabled by this unique device architecture that enables a
      high photoconductive gain of ~10(4) with a response time of several milliseconds.

PMID- 25607923
TI  - Occurrence of synthetic phenolic antioxidants and major metabolites in municipal
      sewage sludge in China.
AB  - Synthetic phenolic antioxidants (SPAs) are one group of widely used additive
      chemicals, which have not yet had focused attention except for a few compounds
      such as 2,6-di-tert-butyl-4-methylphenol (BHT). In this study, the occurrence and
      composition profiles of 12 frequently used SPAs and three BHT metabolites were
      investigated in fifty-six sludge samples collected from individual wastewater
      treatment plants in China. Eleven SPAs were positively found in the sludge
      samples, in which, to our knowledge, eight SPA compounds were identified for the
      first time in the environment. BHT, 4-tert-octylphenol (4-tOP), and 2,4,6-tri
      tert-bultylphenol (AO 246) were the most dominant SPAs in the sludge at mean
      concentrations of 4.14 MUg/g, 374 ng/g, and 98.1 ng/g d.w. (dry weight).
      Meanwhile, three BHT metabolites, including 3,5-di-tert-butyl-4
      hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q), and
      2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone (BHT-quinol), were also
      found in most of the samples (>98.2%) with mean concentrations of 141, 562, and
      225 ng/g d.w., respectively. The activated sludge system (anaerobic, anoxic, and
      oxic tanks) of a wastewater treatment plant was further investigated for the
      removal efficiencies of the SPAs. High removal efficiencies (80.1-89.2%) were
      found for the six detected SPAs in the aqueous phase, while generation of large
      proportions of the three BHT metabolites was also observed. 

PMID- 25607924
TI  - Dynamics of solvent response in methanol-chloroform binary solvent mixture: a
      case of synergistic solvation.
AB  - Steady-state absorption, emission, and femtosecond transient absorption
      spectroscopies were used to ascertain the static and dynamic nature of the
      solvent response of methanol-chloroform binary solvent mixtures of different
      stoichiometric ratios using 4-(dicyanomethylene)-2-methyl-6-(4
      dimethylaminostyryl)-4H-pyran (DCM) as the probe molecule. The appearance of
      synergistic solvation behavior in the steady-state absorption measurements can be
      explained in terms of solvent-solvent interactions through an extended hydrogen
      bonding network. The disappearance of such synergistic behavior in the excited
      state of the DCM dye was recently proposed by us to be due to the weak nature of
      the intermolecular interactions present in binary solvent mixtures (J. Phys.
      Chem. B 2012, 116, 1345). It was anticipated and subsequently confirmed by the
      dynamics of the solvent response that the disruption of the weak interactive
      solvent network is the main reason for the absence of the synergism in the
      excited state. As expected, we observed the slowest dynamics for the mixture with
      X(MeOH) = 0.45, with an average solvation time of 12.03 ps, which is much higher
      than the values for the pure bulk counterparts (?tau(s)?(Methanol) = 4.32 ps and
      ?tau(s)?(Chloroform) = 1.32 ps). The unprecedented slowing of solvation for DCM
      is probably due to the rigid interactive methanol-chloroform solvent system in
      the first solvation shell, followed by solvent rearrangements around the solute
      dipole. Overall interactions present within the methanol-chloroform binary
      solvent mixture furnish clear evidence of solvent association through weak
      hydrogen bonding.

PMID- 25607925
TI  - Liquid phase deposition of a space-durable, antistatic SnO2 coating on Kapton.
AB  - Polyimides are widely used in thermal blankets covering the external surfaces of
      spacecrafts due to their space durability and their thermo-optical properties.
      However, they are susceptible to atomic oxygen (AO) erosion, the main hazard of
      low Earth orbit (LEO), and to electrical charging. This work demonstrates that
      liquid phase deposition (LPD) of 100 nm of tin oxide creates a protective coating
      on Kapton polyimide that has good adherence and is effective in preventing AO
      induced surface erosion and in reducing electrical charging. The as-deposited tin
      oxide induces no significant changes in the original thermo-optical properties of
      the polymer and is effective in preventing electrostatic discharge (ESD). The
      durability of the oxide coating under AO attack was studied using oxygen RF
      plasma. The AO exposure did not result in any significant changes in surface
      morphology, thermo-optical, mechanical, and electrical properties of the tin
      oxide-coated Kapton. The erosion yield of tin oxide-coated Kapton was negligible
      after exposure to 6.4 * 10(20) O atoms.cm(-2) of LEO equivalent AO fluence,
      indicating a complete protection of Kapton by the LPD deposited coating.
      Moreover, the tin oxide coating is flexible enough so that its electrical
      conductivity stays within the desired range of antistatic materials despite
      mechanical manipulations. The advantages of liquid phase deposited oxides in
      terms of their not being line of site limited are well established. We now extend
      these advantages to coatings that reduce electrostatic discharge while still
      providing a high level of protection from AO erosion. 

PMID- 25607926
TI  - Thyroglobulin level in fine-needle aspirates for preoperative diagnosis of
      cervical lymph node metastasis in patients with papillary thyroid carcinoma: two
      different cutoff values according to serum thyroglobulin level.
AB  - BACKGROUND: Measurement of thyroglobulin (Tg) in the washout fluid of fine-needle
      aspirates (FNA-Tg) is useful for diagnosis of lymph node (LN) metastasis in
      papillary thyroid carcinoma (PTC). However, the cutoff value of FNA-Tg in the
      preoperative state is not defined clearly. This study aimed to evaluate the
      optimal cutoff value of preoperative FNA-Tg according to serum Tg level. METHODS:
      FNA-Tg was measured in 135 PTC patients (160 LNs) for preoperative diagnosis of
      cervical LN metastasis. RESULTS: Of the 160 LNs, 119 (74%) were surgically
      removed and 110 (69%) were diagnosed as malignant. When we adopted a FNA-Tg of
      1.0 MUg/L as the cutoff value, the sensitivity and specificity were 99% and 76%,
      respectively. FNA-Tg levels were correlated with serum Tg levels (Pearson's
      coefficient 0.42, p=0.002) and the FNA-Tg levels of 12 of the 50 benign LNs were
      above 1.0 MUg/L. We classified the LNs into two groups according to serum Tg
      level regardless of anti-Tg antibody status: a low Tg group (<=1.0 MUg/L, n=22,
      14%) and a high Tg group (>1.0 MUg/L, n=138, 86%). In the low Tg group, the
      sensitivity and specificity of the FNA-Tg cutoff value of 1.0 MUg/L were 93% and
      100%, respectively. In the high Tg group, the sensitivity and specificity of the
      FNA-Tg cutoff value of 19.0 MUg/L were 93% and 100%, respectively. A Tg ratio
      (FNA-Tg level divided by serum Tg level) of 0.5 gave an improved diagnostic
      performance (sensitivity, 98%; specificity, 98%) in the high Tg group.
      CONCLUSIONS: FNA-Tg levels in the preoperative state are affected by serum Tg
      levels when they exceeded 1.0 MUg/L. For the preoperative diagnosis of metastatic
      cervical LNs, it seems reasonable to employ different cutoff values of FNA-Tg
      depending on serum Tg levels. We propose the use of an optimal cutoff value of
      FNA-Tg of 1.0 MUg/L in patients with low serum Tg levels and a Tg ratio of 0.5 in
      those with high serum Tg levels irrespective of thyroglobulin antibody status.

PMID- 25607927
TI  - Skeletal muscle fibrosis in the mdx/utrn+/- mouse validates its suitability as a
      murine model of Duchenne muscular dystrophy.
AB  - Various therapeutic approaches have been studied for the treatment of Duchenne
      muscular dystrophy (DMD), but none of these approaches have led to significant
      long-term effects in patients. One reason for this observed inefficacy may be the
      use of inappropriate animal models for the testing of therapeutic agents. The mdx
      mouse is the most widely used murine model of DMD, yet it does not model the
      fibrotic progression observed in patients. Other murine models of DMD are
      available that lack one or both alleles of utrophin, a functional analog of
      dystrophin. The aim of this study was to compare fibrosis and myofiber damage in
      the mdx, mdx/utrn+/- and double knockout (dko) mouse models. We used Masson's
      trichrome stain and percentage of centrally-nucleated myofibers as indicators of
      fibrosis and myofiber regeneration, respectively, to assess disease progression
      in diaphragm and gastrocnemius muscles harvested from young and aged wild-type,
      mdx, mdx/utrn+/- and dko mice. Our results indicated that eight week-old
      gastrocnemius muscles of both mdx/utrn+/- and dko hind limb developed fibrosis
      whereas age-matched mdx gastrocnemius muscle did not (p = 0.002). The amount of
      collagen found in the mdx/utrn+/- diaphragm was significantly higher than that
      found in the corresponding diaphragm muscles of wild-type animals, but not of mdx
      animals (p = 0.0003). Aged mdx/utrn+/- mice developed fibrosis in both diaphragm
      and gastrocnemius muscles compared to wild-type controls (p = 0.003). Mdx
      diaphragm was fibrotic in aged mice as well (p = 0.0235), whereas the
      gastrocnemius muscle in these animals was not fibrotic. We did not measure a
      significant difference in collagen staining between wild-type and mdx
      gastrocnemius muscles. The results of this study support previous reports that
      the moderately-affected mdx/utrn+/- mouse is a better model of DMD, and we show
      here that this difference is apparent by 2 months of age. 

PMID- 25607929
TI  - Getting connected: Both associative and semantic links structure semantic memory
      for newly learned persons.
AB  - The present study examined whether semantic memory for newly learned people is
      structured by visual co-occurrence, shared semantics, or both. Participants were
      trained with pairs of simultaneously presented (i.e., co-occurring)
      preexperimentally unfamiliar faces, which either did or did not share
      additionally provided semantic information (occupation, place of living, etc.).
      Semantic information could also be shared between faces that did not co-occur. A
      subsequent priming experiment revealed faster responses for both co-occurrence/no
      shared semantics and no co-occurrence/shared semantics conditions, than for an
      unrelated condition. Strikingly, priming was strongest in the co
      occurrence/shared semantics condition, suggesting additive effects of these
      factors. Additional analysis of event-related brain potentials yielded priming in
      the N400 component only for combined effects of visual co-occurrence and shared
      semantics, with more positive amplitudes in this than in the unrelated condition.
      Overall, these findings suggest that both semantic relatedness and visual co
      occurrence are important when novel information is integrated into person-related
      semantic memory. 

PMID- 25607928
TI  - Functional comparison of induced pluripotent stem cell- and blood-derived
      GPIIbIIIa deficient platelets.
AB  - Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model
      genetic diseases and are a potential source for cell transfusion therapies.
      However, it remains elusive to which extent patient-specific hiPSC-derived cells
      functionally resemble their native counterparts. Here, we generated a hiPSC model
      of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by
      dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy
      and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT
      hiPSC-derived platelets and their peripheral blood equivalents showed absence of
      membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading
      and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets
      recapitulate molecular and functional aspects of the disease and show comparable
      behavior to their native counterparts encouraging the further use of hiPSC-based
      disease models as well as the transition towards a clinical application. 

PMID- 25607930
TI  - Design, synthesis and evaluation of new marine alkaloid-derived pentacyclic
      structures with anti-tumoral potency.
AB  - This work describes the synthesis and biological evaluation of a new heterocyclic
      hybrid derived from the ellipticine and the marine alkaloid makaluvamine A.
      Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12
      and its intermediates 1-11 were evaluated for their in vitro cytotoxic activity
      against different cancer cell lines and tested for their inhibitory activity
      against the human DNA topoisomerase II. The analysis by electrophoresis shows
      that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 uM.
      Compound 9 was found to have an interesting profile, having a cytotoxicity of 15,
      15, 15 and 10 MUM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively,
      without any noticeable toxicity against human fibroblast. 

PMID- 25607931
TI  - Oxidative stress and DNA damage induced by imidacloprid in zebrafish (Danio
      rerio).
AB  - Imidacloprid is a neonicotinoid insecticide that can have negative effects on
      nontarget animals. The present study was conducted to assess the toxicity of
      various imidacloprid doses (0.3, 1.25, and 5 mg/mL) on zebrafish sampled after 7,
      14, 21, and 28 days of exposure. The levels of catalase (CAT), superoxide
      dismutase (SOD), reactive oxygen species (ROS), glutathione-S-transferase (GST),
      and malondialdehyde (MDA) and the extent of DNA damage were measured to evaluate
      the toxicity of imidacloprid on zebrafish. SOD and GST activities were noticeably
      increased during early exposure but were inhibited toward the end of the exposure
      period. In addition, the CAT levels decreased to the control level following
      their elevation during early exposure. High concentrations of imidacloprid (1.25
      and 5 mg/L) induced excessive ROS production and markedly increased MDA content
      on the 21st day of exposure. DNA damage was dose- and time-dependent. In
      conclusion, the present study showed that imidacloprid can induce oxidative
      stress and DNA damage in zebrafish. 

PMID- 25607932
TI  - Guide for developing an information technology investment road map for population
      health management.
AB  - Many health systems recovering from a massive investment in electronic health
      records are now faced with the prospect of maturing into accountable care
      organizations. This maturation includes the need to cooperate with new partners,
      involve substantially new data sources, require investment in additional
      information technology (IT) solutions, and become proficient in managing care
      from a new perspective. Adding to the confusion, there are hundreds of population
      health management (PHM) vendors with overlapping product functions. This article
      proposes an organized approach to investing in PHM IT. The steps include
      assessing the organization's business and clinical goals, establishing
      governance, agreeing on business requirements, evaluating the ability of current
      IT systems to meet those requirements, setting time lines and budgets,
      rationalizing current and future needs and capabilities, and installing the new
      systems in the context of a continuously learning organization. This article will
      help organizations chart their position on the population health readiness
      spectrum and enhance their chances for a successful transition from volume-based
      to value-based care.

PMID- 25607933
TI  - Substance use disorder prevention and treatment in stigmatized patient
      populations: ripe for innovation.

PMID- 25607934
TI  - Preclinical trials for prevention of tumor progression of hepatocellular
      carcinoma by LZ-8 targeting c-Met dependent and independent pathways.
AB  - Hepatocellular carcinoma (HCC) is among the most lethal cancers. Mounting studies
      highlighted the essential role of the HGF/c-MET axis in driving HCC tumor
      progression. Therefore, c-Met is a potential therapeutic target for HCC. However,
      several concerns remain unresolved in c-Met targeting. First, the status of
      active c-Met in HCC must be screened to determine patients suitable for therapy.
      Second, resistance and side effects have been observed frequently when using
      conventional c-Met inhibitors. Thus, a preclinical system for screening the
      status of c-Met signaling and identifying efficient and safe anti-HCC agents is
      urgently required. In this study, immunohistochemical staining of phosphorylated
      c-Met (Tyr1234) on tissue sections indicated that HCCs with positive c-Met
      signaling accounted for approximately 46% in 26 cases. Second, many patient
      derived HCC cell lines were established and characterized according to motility
      and c-Met signaling status. Moreover, LZ8, a medicinal peptide purified from the
      herb Lingzhi, featuring immunomodulatory and anticancer properties, was capable
      of suppressing cell migration and slightly reducing the survival rate of both c
      Met positive and negative HCCs, HCC372, and HCC329, respectively. LZ8 also
      suppressed the intrahepatic metastasis of HCC329 in SCID mice. On the molecular
      level, LZ8 suppressed the expression of c-Met and phosphorylation of c-Met, ERK
      and AKT in HCC372, and suppressed the phosphorylation of JNK, ERK, and AKT in
      HCC329. According to receptor array screening, the major receptor tyrosine kinase
      activated in HCC329 was found to be the epidermal growth factor receptor (EGFR).
      Moreover, tyrosine-phosphorylated EGFR (the active EGFR) was greatly suppressed
      in HCC329 by LZ8 treatment. In addition, LZ8 blocked HGF-induced cell migration
      and c-Met-dependent signaling in HepG2. In summary, we designed a preclinical
      trial using LZ8 to prevent the tumor progression of patient-derived HCCs with c
      Met-positive or -negative signaling. 

PMID- 25607935
TI  - Derivation of hair-inducing cell from human pluripotent stem cells.
AB  - Dermal Papillae (DP) is a unique population of mesenchymal cells that was shown
      to regulate hair follicle formation and growth cycle. During development most DP
      cells are derived from mesoderm, however, functionally equivalent DP cells of
      cephalic hairs originate from Neural Crest (NC). Here we directed human embryonic
      stem cells (hESCs) to generate first NC cells and then hair-inducing DP-like
      cells in culture. We showed that hESC-derived DP-like cells (hESC-DPs) express
      markers typically found in adult human DP cells (e.g., p-75, nestin, versican,
      SMA, alkaline phosphatase) and are able to induce hair follicle formation when
      transplanted under the skin of immunodeficient NUDE mice. Engineered to express
      GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair
      follicles and express appropriate markers. We demonstrated that BMP signaling is
      critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely
      eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed
      as the cell-based treatment for hair loss diseases. Unfortunately human DP cells
      are not suitable for this purpose because they cannot be obtained in necessary
      amounts and rapidly loose their ability to induce hair follicle formation when
      cultured. In this context derivation of functional hESC-DP cells capable of
      inducing a robust hair growth for the first time shown here can become an
      important finding for the biomedical science.

PMID- 25607936
TI  - Characterisation of calcium phosphate crystals on calcified human aortic vascular
      smooth muscle cells and potential role of magnesium.
AB  - BACKGROUND: Cardiovascular disease including vascular calcification (VC) remains
      the leading cause of death in patients suffering from chronic kidney disease
      (CKD). The process of VC seems likely to be a tightly regulated process where
      vascular smooth muscle cells are playing a key role rather than just a mere
      passive precipitation of calcium phosphate. Characterisation of the chemical and
      crystalline structure of VC was mainly led in patients or animal models with CKD.
      Likewise, Mg2+ was found to be protective in living cells although a potential
      role for Mg2+ could not be excluded on crystal formation and precipitation. In
      this study, the crystal formation and the role of Mg2+ were investigated in an in
      vitro model of primary human aortic vascular smooth muscle cells (HAVSMC) with
      physical techniques. METHODOLOGY/PRINCIPAL FINDINGS: In HAVSMC incubated with
      increased Ca x Pi medium, only calcium phosphate apatite crystals (CPA) were
      detected by Micro-Fourier Transform InfraRed spectroscopy (uFTIR) and Field
      Effect Scanning Electron Microscope (FE-SEM) and Energy Dispersive X-ray
      spectrometry (EDX) at the cell layer level. Supplementation with Mg2+ did not
      alter the crystal composition or structure. The crystal deposition was
      preferentially positioned near or directly on cells as pictured by FE-SEM
      observations and EDX measurements. Large uFTIR maps revealed spots of CPA
      crystals that were associated to the cellular layout. This qualitative analysis
      suggests a potential beneficial effect of Mg2+ at 5 mM in noticeably reducing the
      number and intensities of CPA uFTIR spots. CONCLUSIONS/SIGNIFICANCE: For the
      first time in a model of HAVSMC, induced calcification led to the formation of
      the sole CPA crystals. Our data seems to exclude a physicochemical role of Mg2+
      in altering the CPA crystal growth, composition or structure. Furthermore, Mg2+
      beneficial role in attenuating VC should be linked to an active cellular role.

PMID- 25607937
TI  - Two distinct redox intercalation reactions of hydroquinone with porous vanadium
      benzenedicarboxylate MIL-47.
AB  - One of the enticing features of metal-organic frameworks (MOFs) is the potential
      to control the chemical and physical nature of the pores through postsynthetic
      modification. The incorporation of redox active guest molecules inside the pores
      of the framework represents one strategy toward improving the charge transport
      properties of MOFs. Herein, we report the vapor-phase redox intercalation of an
      electroactive organic compound, hydroquinone (H2Q) or benzene-1,4-diol, into the
      channels of the host [V(IV)O(bdc)], (bdc =1,4-benzenedicarboxylate)
      conventionally denoted as MIL-47. The temperatures and especially the atmosphere
      in which the reactions took place were found to determine the products. In
      ambient atmosphere, quinhydrone charge-transfer complexes are formed inside the
      channels. Under anhydrous conditions, the framework itself was functionalized by
      a radical anion species derived from the pyrolysis of hydroquinone. Both cases
      are accompanied by the reduction of V(4+) to V(3+) via single-crystal-to-single
      crystal transformations. The products were characterized by single crystal X-ray
      diffraction, thermogravimetric analysis, infrared spectroscopy, and electron
      paramagnetic resonance spectroscopy. 

PMID- 25607938
TI  - Developing health care workforces for uncertain futures.
AB  - Conventional approaches to health care workforce planning are notoriously
      unreliable. In part, this is due to the uncertainty of the future health milieu.
      An approach to health care workforce planning that accommodates this uncertainty
      is not only possible but can also generate intelligence on which planning and
      consequent development can be reliably based. Drawing on the experience of Health
      Workforce New Zealand, the author outlines some of the approaches being used in
      New Zealand. Instead of relying simply on health care data, which provides a
      picture of current circumstances in health systems, the author argues that
      workforce planning should rely on health care intelligence--looking beyond the
      numbers to build understanding of how to achieve desired outcomes. As health care
      systems throughout the world respond to challenges such as reform efforts, aging
      populations of patients and providers, and maldistribution of physicians (to name
      a few), New Zealand's experience may offer a model for rethinking workforce
      planning to truly meet health care needs.

PMID- 25607939
TI  - A competency-based approach to recruiting, developing, and giving feedback to
      department chairs.
AB  - Academic health centers (AHCs) are under unprecedented pressure, making strong
      leadership during these challenging times critical. Department chairs have
      tremendous influence in their AHCs, yet data indicate that--despite outstanding
      academic credentials--they are often underprepared to take on these important
      leadership roles. The authors sought to improve the approach to recruiting,
      developing, and giving feedback to department chairs at their institution, the
      Indiana University School of Medicine (IUSM), by reorganizing these processes
      around six key leadership competencies: leadership and team development,
      performance and talent management, vision and strategic planning, emotional
      intelligence, communication skills, and commitment to the tripartite mission.
      Over a two-year period (2009-2011), IUSM faculty and administrators developed
      standardized recruitment procedures to assess potential chairs based on the six
      leadership domains, and searches are now streamlined through centralized staff
      support in the dean's office. Additionally, IUSM offers a chair development
      series to support learning around these leadership competencies and to meet the
      stated professional development needs of the chairs. Finally, chairs receive
      structured feedback regarding their leadership (among other considerations)
      through two different assessment instruments, IUSM's Department Chair 360 degrees
      Leadership Survey and IUSM's Faculty Vitality Survey--both of which the dean
      reviews annually. Strategically attending to the way that chairs are selected,
      developed, and given feedback has tremendous potential to increase the success of
      chairs and, in turn, to constructively shape the culture of AHCs.

PMID- 25607940
TI  - The impact of duty hours restrictions on job burnout in internal medicine
      residents: a three-institution comparison study.
AB  - PURPOSE: Internal medicine (IM) residents commonly develop job burnout, which may
      lead to poor academic performance, depression, and medical errors. The extent to
      which duty hours restrictions (DHRs) can mitigate job burnout remains uncertain.
      The July 2011 DHRs created an opportunity to measure the impact of decreased work
      hours on developing burnout in IM residents. METHOD: A survey was administered
      twice to first-year IM residents at three academic medical centers between June
      2011 and July 2012. To estimate the impact of the 2011 DHRs, data from this
      cohort, including demographics, sleepiness, hospital-based patient service
      characteristics, and burnout measures, were compared with data from 2008-2009
      from first-year IM residents at the same institutions. RESULTS: Of eligible
      residents, 128/188 (68%) from the 2011-2012 cohort and 111/180 (62%) from the
      2008-2009 cohort completed both surveys. Year-end burnout prevalence (92/123
      [75%] versus 91/108 [84%], P = .08) and incidence (59/87 [68%] versus 55/68
      [81%], P = .07) did not differ significantly between cohorts. There was no
      difference in year-end prevalence of excessive Epworth sleepiness (72/122 [59%]
      versus 71/108 [66%], P = .29) between cohorts; however, a greater percentage of
      residents who developed burnout in the 2011-2012 cohort reported caring for > 8
      patients on their service (2011-2012 versus 2008-2009) (29/59 [49%] versus 5/34
      [15%], P < .01). CONCLUSIONS: Job burnout and self-reported sleepiness in IM
      resident physicians were unchanged after the 2011 DHRs at three academic
      institutions. Further investigation into the determinants of burnout can inform
      effective interventions.

PMID- 25607941
TI  - What makes a top research medical school? A call for a new model to evaluate
      academic physicians and medical school performance.
AB  - Since the publication of the Flexner Report in 1910, the medical education
      enterprise has undergone many changes to ensure that medical schools meet a
      minimum standard for the curricula and clinical training they offer students.
      Although the efforts of the licensing and accrediting bodies have raised the
      quality of medical education, the educational processes that produce the
      physicians who provide the best patient care and conduct the best biomedical
      research have not been identified. Comparative analyses are powerful tools to
      understand the differences between institutions, but they are challenging to
      carry out. As a result, the analysis performed by U.S. News & World Report
      (USN&WR) has become the default tool to compare U.S. medical schools. Medical
      educators must explore more rigorous and equitable approaches to analyze and
      understand the performance of medical schools. In particular, a better
      understanding and more thorough evaluation of the most successful institutions in
      producing academic physicians with biomedical research careers are needed. In
      this Perspective, the authors present a new model to evaluate medical schools'
      production of academic physicians who advance medicine through basic, clinical,
      translational, and implementation science research. This model is based on
      relevant and accessible objective criteria that should replace the subjective
      criteria used in the current USN&WR rankings system. By fostering a national
      discussion about the most meaningful criteria that should be measured and
      reported, the authors hope to increase transparency of assessment standards and
      ultimately improve educational quality. 

PMID- 25607942
TI  - Research ethics consultation: ethical and professional practice challenges and
      recommendations.
AB  - The complexity of biomedical research has increased considerably in the last
      decade, as has the pace of translational research. This complexity has generated
      a number of novel ethical issues for clinical investigators, institutional review
      boards (IRBs), and other oversight committees. In response, many academic medical
      centers have created formal research ethics consultation (REC) services to help
      clinical investigators and IRBs navigate ethical issues in biomedical research.
      Key functions of a REC service include assisting with research design and
      implementation, providing a forum for deliberative exploration of ethical issues,
      and supplementing regulatory oversight. As increasing numbers of academic
      research institutions establish REC services, there is a pressing need for
      consensus about the primary aims and policies that should guide these activities.
      Establishing clear expectations about the aims and policies of REC services is
      important if REC programs are to achieve their full potential. Drawing on the
      experiences of a Clinical and Translational Science Award Research Ethics
      Consultation Working Group, this article describes three major ethical and
      professional practice challenges associated with the provision of REC: (1)
      managing multiple institutional roles and responsibilities, (2) managing
      sensitive information, and (3) communicating with consultation requestors about
      how these issues are managed. The paper also presents several practical
      strategies for addressing these challenges and enhancing the quality of REC
      services. 

PMID- 25607943
TI  - The patient-as-partner approach in health care: a conceptual framework for a
      necessary transition.
AB  - The prevalence of chronic diseases today calls for new ways of working with
      patients to manage their care. Although patient-centered approaches have
      contributed to significant advances in care and to treatments that more fully
      respect patients' preferences, values, and personal experiences, the reality is
      that health care professionals still hold a monopoly on the role of healer.
      Patients live with their conditions every day and are experts when it comes to
      their own experiences of illness; this expertise should be welcomed, valued, and
      fostered by other members of the care team. The patient-as-partner approach
      embodies the ideal of making the patient a bona fide member of the health care
      team, a true partner in his or her care. Since 2010, the University of Montreal,
      through the Direction of Collaboration and Patient Partnership, has embraced this
      approach. Patients are not only active members of their own health care team but
      also are involved in research and provide valuable training to health sciences
      students. Including patients as full partners in the health care team entails a
      significant shift in both the medical practice and medical education cultures. In
      this perspective, the authors describe this innovative approach to patient care,
      including the conceptual framework used in its development and the main
      achievements of patient partners in education, health care, and research. 

PMID- 25607945
TI  - Health policy, ethics, and the Kansas Legislative Health Academy.
AB  - We describe a unique program, the Kansas Legislative Health Academy, that brings
      together state legislators from across the political spectrum to build their
      capacity in advancing policies that can improve the health of Kansans. To that
      end, the academy helps legislators develop new skills to deliberate the ethics of
      health policy, use systems thinking to understand the long- and short-term
      effects of policy action and inaction, and engage in acts of civic leadership.
      The academy also seeks to foster an environment of respectful open dialogue and
      to build new cross-chamber and cross-party relationships. Among the most
      important outcomes cited by program participants is the value of sustained,
      personal interaction and problem solving with individuals holding differing
      political views. 

PMID- 25607944
TI  - Phytomonas: trypanosomatids adapted to plant environments.
AB  - Over 100 years after trypanosomatids were first discovered in plant tissues,
      Phytomonas parasites have now been isolated across the globe from members of 24
      different plant families. Most identified species have not been associated with
      any plant pathology and to date only two species are definitively known to cause
      plant disease. These diseases (wilt of palm and coffee phloem necrosis) are
      problematic in areas of South America where they threaten the economies of
      developing countries. In contrast to their mammalian infective relatives, our
      knowledge of the biology of Phytomonas parasites and how they interact with their
      plant hosts is limited. This review draws together a century of research into
      plant trypanosomatids, from the first isolations and experimental infections to
      the recent publication of the first Phytomonas genomes. The availability of
      genomic data for these plant parasites opens a new avenue for comparative
      investigations into trypanosomatid biology and provides fresh insight into how
      this important group of parasites have adapted to survive in a spectrum of hosts
      from crocodiles to coconuts. 

PMID- 25607946
TI  - Extent of inhibition of alpha-synuclein aggregation in vitro by SUMOylation is
      conjugation site- and SUMO isoform-selective.
AB  - alpha-Synuclein, the major aggregating protein in Parkinson's disease, can be
      modified by the small protein SUMO, indicating a potential role in disease.
      However, the effects of SUMOylation on alpha-synuclein aggregation remain
      controversial due to heterogeneous nature of the proteins previously
      investigated. Here we used protein semisynthesis to obtain homogeneously
      SUMOylated alpha-synuclein and discovered site- and isoform-dependent effects of
      SUMOylation on alpha-synuclein aggregation. Our results indicate that SUMOylation
      at K102 is a better inhibitor of aggregation than corresponding modification at
      K96 and SUMO1 modification, a better inhibitor than SUMO3. 

PMID- 25607948
TI  - Bicyclobutonium ions in biosynthesis--interconversion of cyclopropyl-containing
      sterols from orchids.
AB  - Theoretical investigation of cyclopropane-to-cyclopropane rearrangements of
      sterols indicates a role for highly delocalized bicyclobutonium ions in
      biosynthesis. 

PMID- 25607947
TI  - Dietary patterns and clinical outcomes in hemodialysis patients in Japan: a
      cohort study.
AB  - BACKGROUND & OBJECTIVES: Little is known about actual dietary patterns and their
      associations with clinical outcomes in hemodialysis patients. We identified
      dietary patterns in hemodialysis patients in Japan and examined associations
      between dietary patterns and clinical outcomes. DESIGN, SETTING, PARTICIPANTS,
      MEASUREMENTS: We used data from 3,080 general-population participants in the
      Hisayama study (year 2007), and data from 1,355 hemodialysis patients in the
      Japan Dialysis Outcomes and Practice Patterns Study (JDOPPS: years 2005-2007).
      Food intake was measured using a brief self-administered diet-history
      questionnaire (BDHQ). To identify food groups with the Hisayama population data,
      we used principal components analysis with Promax rotation. We adjusted the
      resulting food groups for total daily energy intake, and then we used those
      adjusted food-group scores to identify dietary patterns in the JDOPPS patients by
      cluster analysis (Ward's method). We then used Cox regression to examine the
      association between dietary patterns and a composite of adverse clinical
      outcomes: hospitalization due to cardiovascular disease or death due to any
      cause. RESULTS: We identified three food groups: meat, fish, and vegetables.
      Using those groups we then identified three dietary patterns: well-balanced,
      unbalanced, and other. After adjusting for potential confounders, we found an
      association between an unbalanced diet and important clinical events (hazard
      ratio 1.90, 95% C.I. 1.19-3.04). CONCLUSIONS: Hemodialysis patients whose diet
      was unbalanced were more likely to have adverse clinical outcomes. Thus
      hemodialysis patients might benefit not only from portion control, but also from
      a diet that is well-balanced diet with regard to the food groups identified here
      as meat, fish, and vegetables.

PMID- 25607949
TI  - Probing deactivation pathways of DNA nucleobases by two-dimensional electronic
      spectroscopy: first principles simulations.
AB  - The SOS//QM/MM [Rivalta et al., Int. J. Quant. Chem., 2014, 114, 85] method
      consists of an arsenal of computational tools allowing accurate simulation of one
      dimensional (1D) and bi-dimensional (2D) electronic spectra of monomeric and
      dimeric systems with unprecedented details and accuracy. Prominent features like
      doubly excited local and excimer states, accessible in multi-photon processes, as
      well as charge-transfer states arise naturally through the fully quantum
      mechanical description of the aggregates. In this contribution the SOS//QM/MM
      approach is extended to simulate time-resolved 2D spectra that can be used to
      characterize ultrafast excited state relaxation dynamics with atomistic details.
      We demonstrate how critical structures on the excited state potential energy
      surface, obtained through state-of-the-art quantum chemical computations, can be
      used as snapshots of the excited state relaxation dynamics to generate spectral
      fingerprints for different de-excitation channels. The approach is based on high
      level multi-configurational wavefunction methods combined with non-linear
      response theory and incorporates the effects of the solvent/environment through
      hybrid quantum mechanics/molecular mechanics (QM/MM) techniques. Specifically,
      the protocol makes use of the second-order Perturbation Theory (CASPT2) on top of
      Complete Active Space Self Consistent Field (CASSCF) strategy to compute the high
      lying excited states that can be accessed in different 2D experimental setups. As
      an example, the photophysics of the stacked adenine-adenine dimer in a double
      stranded DNA is modeled through 2D near-ultraviolet (NUV) spectroscopy. 

PMID- 25607950
TI  - DNMT3B7 expression promotes tumor progression to a more aggressive phenotype in
      breast cancer cells.
AB  - Epigenetic changes, such as DNA methylation, have been shown to promote breast
      cancer progression. However, the mechanism by which cancer cells acquire and
      maintain abnormal DNA methylation is not well understood. We have previously
      identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed
      in virtually all cancer cell lines but at very low levels in normal cells.
      Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express
      increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating
      that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data
      gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is
      increased in breast cancer patient tissues compared to normal tissue. To
      determine the mechanism by which DNMT3B7 was functioning in breast cancer cells,
      two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably
      transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to
      hypermethylation and down-regulation of E-cadherin, altered localization of beta
      catenin, as well as increased adhesion turnover, cell proliferation, and
      anchorage-independent growth. The novel results presented in this study suggest a
      role for DNMT3B7 in the progression of breast cancer to a more aggressive state
      and the potential for future development of novel therapeutics. 

PMID- 25607951
TI  - Metformin: a modulator of bevacizumab activity in cancer? A case report.
AB  - Recurrent type I endometrial cancer (EC) has poor prognosis and demands novel
      therapeutic approaches. Bevacizumab, a VEGF-A neutralizing monoclonal antibody,
      has shown clinical activity in this setting. To our knowledge, however, although
      some diabetic cancer patients treated with bevacizumab may also take metformin,
      whether metformin modulates response to anti-VEGF therapy has not yet been
      investigated. Here, we report the case of a patient with advanced EC treated,
      among other drugs, with bevacizumab in combination with metformin. The patient
      affected by relapsed EC G3 type 1, presented in march 2010 with liver, lungs and
      mediastinic metastases. After six cycles of paclitaxel and cisplatin she
      underwent partial response. Later on, she had disease progression notwithstanding
      administration of multiple lines of chemotherapy. In march 2013, due to brain
      metastases with coma, she began steroid therapy with development of secondary
      diabetes. At this time, administration of Bevacizumab plus Metformin improved her
      performance status. CT scans performed in this time window showed reduced
      radiologic density of the lung and mediastinic lesions and of liver disease,
      suggestive of increased tumor necrosis. Strong (18)F-FDG uptake by PET imaging
      along with high levels of monocarboxylate transporter 4 and lack of liver kinase
      B1 expression in liver metastasis, highlighted metabolic features previously
      associated with response to anti-VEGF therapy and phenformin in preclinical
      models. However, clinical benefit was transitory and was followed by rapid and
      fatal disease progression. These findings--albeit limited to a single case-
      suggest that tumors lacking LKB1 expression and/or endowed with an highly
      glycolytic phenotype might develop large necrotic areas following combined
      treatment with metformin plus bevacizumab. As metformin is widely used among
      diabetes patients as well as in ongoing clinical trials in cancer patients, these
      results deserve further clinical investigation.

PMID- 25607952
TI  - Heterosis and combining ability estimates in isoflavone content using different
      parental soybean accessions: wild soybean, a valuable germplasm for soybean
      breeding.
AB  - Isoflavone, a group of secondary metabolites in soybean, is beneficial to human
      health. Improving isoflavone content in soybean seeds has become one of the most
      important breeding objectives. However, the narrow genetic base of soybean
      cultivars hampered crop improvement. Wild soybean is an extraordinarily important
      gene pool for soybean breeding. In order to select an optimal germplasm for
      breeding programs to increase isoflavone concentration, 36 F1 soybean progenies
      from different parental accessions (cultivars, wild, Semi-wild and Interspecific)
      with various total isoflavone (TIF) concentration (High, Middle, Low) were
      analyzed for their isoflavone content. Results showed that male parents, except
      for Cultivars, showed positive GCA effects. In particular, wild soybean had
      higher positive GCA effects for TIF concentration. Both MP and BP heterosis value
      declined in the hybrid in which male parents were wild soybean, semi-wild
      soybean, interspecific offspring and cultivar in turn. In general, combining
      ability and heterosis in hybrids which had relative higher TIF concentration
      level parents showed better performance than those which had lower TIF
      concentration level parents. These results indicated characteristics of
      isoflavone content were mainly governed by additive type of gene action, and wild
      relatives could be utilized for breeding of soybean cultivars with this trait. A
      promising combination was found as the best potential hybrid for isoflavone
      content improvement. 

PMID- 25607953
TI  - Transcriptional responses to sucrose mimic the plant-associated life style of the
      plant growth promoting endophyte Enterobacter sp. 638.
AB  - Growth in sucrose medium was previously found to trigger the expression of
      functions involved in the plant associated life style of the endophytic bacterium
      Enterobacter sp. 638. Therefore, comparative transcriptome analysis between
      cultures grown in sucrose or lactate medium was used to gain insights in the
      expression levels of bacterial functions involved in the endophytic life style of
      strain 638. Growth on sucrose as a carbon source resulted in major changes in
      cell physiology, including a shift from a planktonic life style to the formation
      of bacterial aggregates. This shift was accompanied by a decrease in
      transcription of genes involved in motility (e.g., flagella biosynthesis) and an
      increase in the transcription of genes involved in colonization, adhesion and
      biofilm formation. The transcription levels of functions previously suggested as
      being involved in endophytic behavior and functions responsible for plant growth
      promoting properties, including the synthesis of indole-acetic acid, acetoin and
      2,3-butanediol, also increased significantly for cultures grown in sucrose
      medium. Interestingly, despite an abundance of essential nutrients transcription
      levels of functions related to uptake and processing of nitrogen and iron became
      increased for cultures grown on sucrose as sole carbon source. Transcriptome data
      were also used to analyze putative regulatory relationships. In addition to the
      small RNA csrABCD regulon, which seems to play a role in the physiological
      adaptation and possibly the shift between free-living and plant-associated
      endophytic life style of Enterobacter sp. 638, our results also pointed to the
      involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant
      associated life style. Targeted mutagenesis was used to confirm this role and
      showed that compared to wild-type Enterobacter sp. 638 a DeltarcsB mutant was
      affected in its plant growth promoting ability.

PMID- 25607956
TI  - Antireflection coatings designed by the average uniform algorithm for thin film
      solar cells.
AB  - Effective coatings improve the performance of any device designed to emit or
      collect light over a range of angles and wavelengths. Improved broadband and wide
      angle antireflection coatings (ARCs) are a simple and direct way to improve solar
      cell performance. In this paper we demonstrate a multilayered ARC optimized using
      a new meta-heuristic algorithm called the average uniform algorithm (AUA).
      Comparison between the well-known genetic algorithm and the AUA showed that both
      achieved similar results but the AUA converged much faster. The coating optimized
      by AUA for broadband and wide-angle emission is applied to a copper zinc tin
      sulfide based thin film solar cell by co-sputtering of high and low refractive
      index material. A significant improvement in efficiency was observed over wide
      angle and bandwidth with a typical improvement of 15% over the uncoated solar
      cell. This AUA methodology is proven to be an efficient method for design of
      general ARCs. 

PMID- 25607954
TI  - Systemic expression of Kaposi sarcoma herpesvirus (KSHV) Vflip in endothelial
      cells leads to a profound proinflammatory phenotype and myeloid lineage
      remodeling in vivo.
AB  - KSHV is the causative agent of Kaposi sarcoma (KS), a spindle-shaped endothelial
      cell neoplasm accompanied by an inflammatory infiltrate. To evaluate the role of
      KSHV vFLIP in the pathogenesis of KS, we constructed mice with inducible
      expression of vFLIP in endothelial cells. Abnormal cells with endothelial marker
      expression and fusiform appearance were observed in several tissues reminiscent
      of the spindle cells found in KS. Serum cytokines displayed a profound
      perturbation similar to that described in KSHV inflammatory cytokine syndrome
      (KICS), a recently described clinical condition characterized by elevated IL6 and
      IL10. An increased myeloid component with suppressive immune phenotype was found,
      which may contribute to functional changes in the microenvironment and cellular
      heterogeneity as observed in KS. These mice represent the first in vivo
      demonstration that vFLIP is capable of inducing vascular abnormalities and
      changes in host microenvironment with important implications for understanding
      the pathogenesis and treating KSHV-associated diseases. 

PMID- 25607957
TI  - Low-loss, efficient, wide-angle 1  *  4 power splitter at ~1.55  MUm wavelengths
      for four play applications built with a monolithic photonic crystal slab.
AB  - We exhibit a low-loss, efficient, and wide-angle 1*4 power splitter based on a
      silicon monolithic photonic crystal slab with triangular lattice air holes. A
      distinctive power-splitting ratio can be obtained depending on the hole shift in
      the bending region and the structure adjustment at the junction area with regard
      to the power splitter designed. Simulation results achieved with a rigorous
      finite-difference time-domain technique show that the TE-polarized light is
      designed to ensure single-mode operation and the transmitted power is distributed
      almost equally, with a total transmission of 93.4% at the 1550 nm optical
      operation wavelength. Furthermore, we demonstrate ultralow-loss output of the
      optimized power splitter, with a transmittance above 22.5% (-6.48  dB) achieved
      in the ranges of 1524-1594 and 1610-1620 nm, which cover the entire C-band and a
      large portion of the L-band of optical communication. 

PMID- 25607955
TI  - Rift Valley fever virus infection in golden Syrian hamsters.
AB  - Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe
      disease and abortion in a variety of livestock species and a range of disease in
      humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and
      blindness. The natural transmission cycle involves mosquito vectors, but exposure
      can also occur through contact with infected fluids and tissues. The lack of
      approved antiviral therapies and vaccines for human use underlies the importance
      of small animal models for proof-of-concept efficacy studies. Several mouse and
      rat models of RVFV infection have been well characterized and provide useful
      systems for the study of certain aspects of pathogenesis, as well as antiviral
      drug and vaccine development. However, certain host-directed therapeutics may not
      act on mouse or rat pathways. Here, we describe the natural history of disease in
      golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain
      of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV
      challenge. High titer viremia and substantial viral loads were observed in most
      tissues examined; however, histopathology and immunostaining for RVFV antigen
      were largely restricted to the liver. Acute hepatocellular necrosis associated
      with a strong presence of viral antigen in the hepatocytes indicates that
      fulminant hepatitis is the likely cause of mortality. Further studies to assess
      the susceptibility and disease progression following respiratory route exposure
      are warranted. The use of the hamsters to model RVFV infection is suitable for
      early stage antiviral drug and vaccine development studies. 

PMID- 25607958
TI  - First-order approximation error analysis of Risley-prism-based beam directing
      system.
AB  - To improve the performance of a Risley-prism system for optical detection and
      measuring applications, it is necessary to be able to determine the direction of
      the outgoing beam with high accuracy. In previous works, error sources and their
      impact on the performance of the Risley-prism system have been analyzed, but
      their numerical approximation accuracy was not high. Besides, pointing error
      analysis of the Risley-prism system has provided results for the case when the
      component errors, prism orientation errors, and assembly errors are certain. In
      this work, the prototype of a Risley-prism system was designed. The first-order
      approximations of the error analysis were derived and compared with the exact
      results. The directing errors of a Risley-prism system associated with wedge
      angle errors, prism mounting errors, and bearing assembly errors were analyzed
      based on the exact formula and the first-order approximation. The comparisons
      indicated that our first-order approximation is accurate. In addition, the
      combined errors produced by the wedge-angle errors and mounting errors of the two
      prisms together were derived and in both cases were proved to be the sum of
      errors caused by the first and the second prism separately. Based on these
      results, the system error of our prototype was estimated. The derived formulas
      can be implemented to evaluate beam directing errors of any Risley-prism beam
      directing system with a similar configuration. 

PMID- 25607959
TI  - High efficiency, linearly polarized, directly diode-pumped Er:YAG laser at 1617 
      nm.
AB  - An efficient, directly diode-pumped Er:YAG laser at 1617 nm was demonstrated. A
      folding mirror with high reflectivity for the s-polarized light at the laser
      wavelength was used to achieve a linearly polarized laser. A maximum continuous
      wave output power of 7.73 W was yielded under incident pump power of 50.57 W, and
      the optical conversion efficiency with respect to incident pump power was
      ~15.28%, which was the highest optical conversion efficiency with directly diode
      pumped Er:YAG lasers up to now; in Q-switched operation, the maximum pulse energy
      of 7.82 mJ was generated with pulse duration of about 80 ns at a pulse repetition
      frequency of 500 Hz. 

PMID- 25607960
TI  - All-optical logical gates based on pump-induced resonant nonlinearity in an
      erbium-doped fiber coupler.
AB  - In this paper, we theoretically investigate all-optical logical gates based on
      the pump-induced resonant nonlinearity in an erbium-doped fiber coupler. The
      resonant nonlinearity yielded by the optical transitions between the (4)I(15/2)
      states and (4)I(13/2) states in Er(3+) induces the refractive index to change,
      which leads to switching between two output ports. First, we do a study on the
      switching performance, and calculate the extinction ratio (Xratio) of the device.
      Second, using the Xratio, we obtain the truth tables of the device. The results
      reveal that compared with other undoped nonlinear couplers, the erbium-doped
      fiber coupler can drop the switching threshold power. We also obtain different
      logic gates and logic operations in the cases of the same phase and different
      phase of two initial signals by changing the pump power.

PMID- 25607961
TI  - Polarization-dependent bandwidth in low-index plasmonic metamaterials.
AB  - We investigate the visible range, less-than-one index bandwidth, n(lambda)<1, of
      an optical metamaterial structure composed of plasmonic gold nanoparticles, and
      show that it is highly dependent on the polarization of incident light. The full
      wave finite element method is used to obtain the spectral characteristics of the
      structure. We have found spectral bands over which the structure shows the
      desired low index. Further, a possible increase of the bandwidth by as much as
      270% is demonstrated by a change in the incident polarization that extends the
      low-index bandwidth range (503-600 nm) asymmetrically into a wider range (485-750
      nm) covering longer wavelengths close to near infrared. This asymmetric overlap
      might have the potential for new optical applications. 

PMID- 25607962
TI  - Generation and transmission of 3 * 3 W-Band multi-input multi-output orthogonal
      frequency division multiplexing-radio-over-fiber signals using micro-ring
      resonators.
AB  - Using the micro-ring resonator (MRR) system, the single and multi-carriers at
      frequencies of f(1)=192.898, f(2)=192.990, f(3)=193.1, f(4)=193.315, and
      f(5)=193.537  THz with a free spectral range (FSR) of 92, 110, 215, and 222 GHz,
      respectively, are generated to be suitable for a radio-over-fiber (RoF) system
      based on multi-input multi-output (MIMO) with orthogonal frequency division
      multiplexing (OFDM). Demonstrated are the concepts of all-optical MIMO signal
      generation and its transmission over a 50 km single mode fiber (SMF) optical link
      and an up to 3 m wireless link. Sixty-four multi-carriers are used in the all
      optical generation of three MIMO W-Band RF signals, where the single carriers
      (f(3)-f(5)) transport the signals over the RoF link. The bit error rate (BER) of
      the overall system performance is discussed; thus, the transmission of MIMO
      signals is feasible for up to an SMF path 50 km long and a wireless distance of 3
      m.

PMID- 25607963
TI  - 1.5  kW, near-diffraction-limited, high-efficiency, single-end-pumped all-fiber
      integrated laser oscillator.
AB  - We report a monolithic single-end-pumped all-fiber laser oscillator with 1.5 kW
      power output operating at 1070 nm. The laser scheme design and fiber parameter
      selection are based on our theoretical analysis through one rate equation model
      consisting of changing pump wavelengths. The laser oscillator is pumped by 49
      fiber-pigtailed 915 nm laser diodes with power of 50 W each through two stage
      combiners. The measured laser power is 1520 W at the pump power of 2054 W, and
      the corresponding optical-to-optical efficiency is 74%, in agreement with
      numerical simulation. Stimulated Raman scattering is observed when the laser
      power reaches 1030 W and the power ratio of Raman power is 4% at maximum output
      power. The experimental results show that the beam qualities represented by the
      M(2) factor are less than 1.2 at all pump power levels.

PMID- 25607964
TI  - Recent results of medium wave infrared compressive sensing.
AB  - The application of compressive sensing (CS) for imaging has been extensively
      investigated and the underlying mathematical principles are well understood. The
      theory of CS is motivated by the sparse nature of real-world signals and images,
      and provides a framework in which high-resolution information can be recovered
      from low-resolution measurements. This, in turn, enables hardware concepts that
      require much fewer detectors than a conventional sensor. For infrared imagers
      there is a significant potential impact on the cost and footprint of the sensor.
      When smaller focal plane arrays (FPAs) to obtain large images are allowed, large
      formats FPAs are unnecessary. From a hardware standpoint, this benefit is
      independent of the actual level of compression and effective data rate reduction,
      which depend on the choice of codes and information recovery algorithm. Toward
      this end, we used a CS testbed for mid-wave infrared (MWIR) to experimentally
      show that information at high spatial resolution can be successfully recovered
      from measurements made with a small FPA. We describe the highly parallel and
      scalable CS architecture of the testbed, and its implementation using a
      reflective spatial light modulator and a focal plane array with variable pixel
      sizes. We also discuss the impact of real-world devices and the effect of sensor
      calibration that must be addressed in practice. Finally, we present preliminary
      results of image reconstruction, which demonstrate the testbed operation. These
      results experimentally confirm that high-resolution spatial information (for
      tasks such as imaging and target detection) can be successfully recovered from
      low-resolution measurements. We also discuss the potential system-level benefits
      of CS for infrared imaging, and some of the challenges that must be addressed in
      future infrared CS imagers designs. 

PMID- 25607965
TI  - Design of compact polarization rotator using simple silicon nanowires.
AB  - In this paper, an ultracompact design of a polarization rotator (PR) based on a
      silicon-on-insulator (SOI) platform is presented. The design contains two simple
      silicon nanowires but with unequal width, which will be easier to fabricate. It
      is shown here that a low-loss, wide-bandwidth, and 52.8-MUm-long compact PR with
      polarization cross talk of -20  dB can be achieved. A full-vectorial finite
      element method and the least-squares boundary residual method are used to study
      the effects of the fabrication tolerances. This design shows reasonably stable
      performances. 

PMID- 25607966
TI  - Quantum efficiency measurements of an x-ray charge-coupled device in the 2-10 
      keV spectral region by means of a double crystal monochromator coupled to an x
      ray tube.
AB  - The Atomic Energy Commission has set up a laboratory dedicated to the calibration
      of x-ray cameras mainly used in the Laser MegaJoule Facility in the Bordeaux
      region of France. Thanks to a double crystal monochromator specifically designed
      to perform such calibration, we calibrated a thinned, back-illuminated x-ray CCD
      manufactured by Roper Scientific Inc. over the 2.2-8.9 keV spectral region.
      Quantum efficiency results are in good agreement with those of previous works. To
      explain slight differences, we studied the difference between monochromatization
      methods performed either using a crystal monochromator or filters. Results showed
      that the latter method appears to be too dependent on the x-ray source parameters
      to perform accurate and relevant calibration on x-ray cameras. 

PMID- 25607967
TI  - Self-written waveguides in a dry acrylamide/polyvinyl alcohol photopolymer
      material.
AB  - For the first time it is demonstrated that permanent optical waveguides can be
      self-written in a solid acrylamide/polyvinyl alcohol photopolymer material. The
      novel (to our knowledge) technique used to prepare the polymeric medium used is
      described. It is demonstrated that the resulting waveguides formed can be used to
      guide different wavelengths. A standard theoretical model is used to predict both
      the evolution of the light intensity distribution and the channel formation
      inside the material during the exposure. The experimental results and the
      numerical simulations are compared, and good agreement is obtained. 

PMID- 25607968
TI  - Tomographic laser absorption spectroscopy using Tikhonov regularization.
AB  - The application of tunable diode laser absorption spectroscopy (TDLAS) to flames
      with nonhomogeneous temperature and concentration fields is an area where only
      few studies exist. Experimental work explores the performance of tomographic
      reconstructions of species concentration and temperature profiles from wavelength
      modulated TDLAS measurements within the plume of an axisymmetric McKenna burner.
      Water vapor transitions at 1391.67 and 1442.67 nm are probed using calibration
      free wavelength modulation spectroscopy with second harmonic detection (WMS-2f).
      A single collimated laser beam is swept parallel to the burner surface, where
      scans yield pairs of line-of-sight (LOS) data at multiple radial locations.
      Radial profiles of absorption data are reconstructed using Tikhonov regularized
      Abel inversion, which suppresses the amplification of experimental noise that is
      typically observed for reconstructions with high spatial resolution. Based on
      spectral data reconstructions, temperatures and mole fractions are calculated
      point-by-point. Here, a least-squares approach addresses difficulties due to
      modulation depths that cannot be universally optimized due to a nonuniform
      domain. Experimental results show successful reconstructions of temperature and
      mole fraction profiles based on two-transition, nonoptimally modulated WMS-2f and
      Tikhonov regularized Abel inversion, and thus validate the technique as a viable
      diagnostic tool for flame measurements. 

PMID- 25607969
TI  - Enhanced luminous efficiency of phosphor-converted LEDs by using back reflector
      to increase reflectivity for yellow light.
AB  - To obtain high reflectivity over a broad range of green, yellow, and red light as
      well as blue light incidents from a particular angular range and further increase
      the luminous efficiency of a phosphor-converted white LED packaging module, a
      novel back hybrid reflector including a SiO(2) total internal reflection layer
      (TIR), five-pair SiO(2)/TiO(2) double distributed Bragg reflector (DBR) stacks,
      and a gold (Au) metallic mirror was designed and fabricated. The double DBR
      stacks have layers configured to reflect green, yellow, and red light as well as
      blue light, which includes a first portion where the thickness of the layers are
      relatively larger, and also includes a second portion where the thickness of the
      layers is relatively smaller. Light that is passing toward the hybrid reflector
      at angles greater than the critical angle (56 degrees ) is reflected by the
      SiO(2) TIR layer at the sapphire/SiO(2) interface, whereas the light that passes
      through the SiO(2) TIR layer with incident angles between 0 degrees  and 56
      degrees  is reflected by the double DBR stacks. The overall hybrid reflector can
      ensure a reflectivity of more than 95% in both the blue light wavelength region
      and the yellow light wavelength region. The obtained higher reflectivity in the
      yellow light wavelength region will benefit the phosphor-converted LEDs because
      yellow light backscattered by phosphor particles is reflected upward.

PMID- 25607970
TI  - Effects of astigmatism on spectra and polarization of aberrant electromagnetic
      nonuniformly correlated beams in turbulent ocean.
AB  - Analytical formulas are derived, for the cross spectral density matrix of
      electromagnetic nonuniformly correlated (EMUNC) beams, with astigmatic aberration
      propagating through oceanic turbulence. We investigate the effects of astigmatism
      on the spectral density, and the spectral degree of polarization, in great
      detail. It can be seen that, unlike for an aberration-free case, the lateral
      shifted intensity maximum (of an astigmatic EMUNC beam) does not return back to
      the on-axis position, after propagating at sufficiently large distances in the
      turbulence. Furthermore, in the far-zone, the deviation of its maximum value
      (from the optical axis) gradually increases, in accordance with growing
      propagation distance. 

PMID- 25607971
TI  - Rayleigh beacon for measuring the surface profile of a radio telescope.
AB  - Millimeter-wavelength Rayleigh scattering from water droplets in a cloud is
      proposed as a means of generating a bright beacon for measuring the surface
      profile of a radio telescope. A lambda=3  mm transmitter, with an output power of
      a few watts, illuminating a stratiform cloud, can generate a beacon with the same
      flux as Mars in 10 GHz bandwidth, but the beacon has a narrow line width, so it
      is extremely bright. The key advantage of the beacon is that it can be used at
      any time, and positioned anywhere in the sky, as long as there are clouds. 

PMID- 25607972
TI  - On the precision of absolute sensitivity calibration and specifics of
      spectroscopic quantities interpretation in tokamaks.
AB  - Typical situations, which can be met during the process of absolute calibration,
      are shown in the case of a visible light observation system for the COMPASS
      tokamak. Technical issues and experimental limitations of absolute measurements
      connected with tokamak operation are discussed. 

PMID- 25607973
TI  - Impact of device geometry on the imaging characteristics of an intravascular
      photoacoustic catheter.
AB  - A basic requirement for intravascular photoacoustic (IVPA) imaging catheters is
      that the delivery of light lies within the ultrasonic field of view. Size and
      manufacturing constraints favor probe designs with offset optical and acoustic
      beams. This noncollinear dual beam arrangement leads to a curved PA point spread
      function (PSF). In this work, we characterize the three-dimensional shape of the
      PSF for IVPA imaging in clear and optically scattering media. We show that the
      product of the two beam profiles can accurately model the measured peak response
      in clear and scattering media. We discuss the impact of the PSF shape and its
      relation to probe construction. We test the imaging capability of the catheter on
      a phantom and a human artery ex vivo. 

PMID- 25607974
TI  - Silicon wire grid polarizer for ultraviolet applications.
AB  - We present a silicon wire grid polarizer operating down to a wavelength of 300
      nm. Besides metallic grating materials, semiconductors also offer appropriate
      material properties to realize wire grid polarizers in the ultraviolet (UV)
      spectral range. The presented polarizer with a period of 140 nm was realized by
      means of electron beam lithography and dry etching using amorphous silicon as the
      grating material. At a wavelength of 365 nm, a transmission of 42% and an
      extinction ratio of 90 (19.5 dB) are measured. The spectral bandwidth of these
      polarizers in the UV-spectral range is about 100 nm. 

PMID- 25607975
TI  - Investigation of a macrobending micro-plastic optical fiber for refractive index
      sensing.
AB  - This paper investigates a refractive index (RI) sensor based on a macrobending
      micro-plastic optical fiber (m-POF), which is used as a sensitive probe. The m
      POFs are fabricated from commercial POFs using a heating and pulling method. The
      m-POFs have diameters of approximately 20-40 MUm and act as multimode fibers at
      visible wavelengths. The macrobending structure of the m-POFs is simulated and
      optimized using the ray tracing method. The RI sensitivity and the range of RI
      measurements are affected by the structure parameter R/rho, which is the ratio of
      the radius of curvature of the macrobending fiber to the radius of the fiber
      itself. A linear RI sensing response is obtained when R/rho=20 and the
      sensitivity reaches 500%/RIU. The experimental results coincide well with the
      simulation results. 

PMID- 25607976
TI  - Transport of intensity phase imaging in the presence of curl effects induced by
      strongly absorbing photomasks.
AB  - We report theoretical and experimental results for imaging of electromagnetic
      phase edge effects in lithography photomasks. Our method starts from the
      transport of intensity equation (TIE), which solves for phase from through-focus
      intensity images. Traditional TIE algorithms make an implicit assumption that the
      underlying in-plane power flow is curl-free. Motivated by our current study, we
      describe a practical situation in which this assumption breaks down. Strong
      absorption gradients in mask features interact with phase edges to contribute a
      curl to the in-plane Poynting vector, causing severe artifacts in the phase
      recovered. We derive how curl effects are coupled into intensity measurements and
      propose an iterative algorithm that not only corrects the artifacts, but also
      recovers missing curl components. 

PMID- 25607977
TI  - Nodal line-scanning method for maskless optical lithography.
AB  - Maskless optical lithography can improve the economics and performance of multi
      patterning by eliminating photomasks and by simplifying the lithography exposure
      technology. It could also potentially eliminate the need for multi-patterning by
      enabling dual-wavelength, nonlinear optical recording methods. High-resolution,
      maskless patterning can be achieved with a scanned-spot-array system in which
      modulated, diffraction-limited focus spots write the exposure pattern. Each spot
      has a central zero-intensity interference null along a line parallel to the scan
      direction for printing sub-resolution line patterns. High throughput can be
      achieved at the comparatively low repetition rate of excimer lasers (e.g., 6
      kHz). The low repetition rate simplifies the optical modulation technology,
      enabling the use of supplemental modulation controls including dynamic gray-level
      and beam-centration controls for resolution enhancement. 

PMID- 25607978
TI  - Advances in lithography: introduction to the feature.
AB  - Optical projection lithography has been the key technology for the ongoing
      miniaturization in semiconductor devices over the past 40 years. This issue
      features original research covering mask and image modeling methods and
      computational techniques for various inverse problems in advanced lithography,
      including source and mask optimization, wavefront retrieval, and design of
      Fresnel lenses. 

PMID- 25607979
TI  - Correction: Identification and Expression Profiling of MicroRNAs in the Brain,
      Liver and Gonads of Marine Medaka (Oryzias melastigma) and in Response to
      Hypoxia.

PMID- 25607980
TI  - Nuclear-translocated endostatin downregulates hypoxia inducible factor-1alpha
      activation through interfering with Zn(II) homeostasis.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is key in tumor progression and
      aggressiveness as it regulates a series of genes involved in angiogenesis and
      anaerobic metabolism. Previous studies have shown that the transcriptional levels
      of HIF-1alpha may be downregulated by endostatin. However, the molecular
      mechanism by which endostatin represses HIF-1alpha expression remains unknown.
      The current study investigated the mechanism by which nuclear-translocated
      endostatin suppresses HIF-1alpha activation by disrupting Zn(II) homeostasis.
      Endostatin was observed to downregulate HIF-1alpha expression at mRNA and protein
      levels. Blockage of endostatin nuclear translocation by RNA interference of
      importin alpha1/beta1 or ectopic expression of NLS-deficient mutant nucleolin in
      human umbilical vein endothelial cells co-transfected with small interfering (si)
      nucleolin siRNA compromises endostatin-reduced HIF-1alpha expression. Nuclear
      translocated apo-endostatin, but not holo-endostatin, significantly disrupts the
      interaction between CBP/p300 and HIF-1alpha by disturbing Zn(II) homeostasis,
      which leads to the transcriptional inactivation of HIF-1alpha. The results reveal
      mechanistic insights into the method by which nuclear-translocated endostatin
      downregulates HIF-1alpha activation and provides a novel way to investigate the
      function of endostatin in endothelial cells.

PMID- 25607982
TI  - Chemical and toxicological evolution of carbon nanotubes during atmospherically
      relevant aging processes.
AB  - The toxicity of carbon nanotubes (CNTs) has received significant attention due to
      their usage in a wide range of commercial applications. While numerous studies
      exist on their impacts in water and soil ecosystems, there is a lack of
      information on the exposure to CNTs from the atmosphere. The transformation of
      CNTs in the atmosphere, resulting in their functionalization, may significantly
      alter their toxicity. In the current study, the chemical modification of single
      wall carbon nanotubes (SWCNTs) via ozone and OH radical oxidation is investigated
      through studies that simulate a range of expected tropospheric particulate matter
      (PM) lifetimes, in order to link their chemical evolution to toxicological
      changes. The results indicate that the oxidation favors carboxylic acid
      functionalization, but significantly less than other studies performed under
      nonatmospheric conditions. Despite evidence of functionalization, neither O3 nor
      OH radical oxidation resulted in a change in redox activity (potentially giving
      rise to oxidative stress) or in cytotoxic end points. Conversely, both the redox
      activity and cytotoxicity of SWCNTs significantly decreased when exposed to
      ambient urban air, likely due to the adsorption of organic carbon vapors. These
      results suggest that the effect of gas-particle partitioning of organics in the
      atmosphere on the toxicity of SWCNTs should be investigated further. 

PMID- 25607981
TI  - New look at hemoglobin allostery.

PMID- 25607983
TI  - Generation of silver standard concept annotations from biomedical texts with
      special relevance to phenotypes.
AB  - Electronic health records and scientific articles possess differing linguistic
      characteristics that may impact the performance of natural language processing
      tools developed for one or the other. In this paper, we investigate the
      performance of four extant concept recognition tools: the clinical Text Analysis
      and Knowledge Extraction System (cTAKES), the National Center for Biomedical
      Ontology (NCBO) Annotator, the Biomedical Concept Annotation System (BeCAS) and
      MetaMap. Each of the four concept recognition systems is applied to four
      different corpora: the i2b2 corpus of clinical documents, a PubMed corpus of
      Medline abstracts, a clinical trails corpus and the ShARe/CLEF corpus. In
      addition, we assess the individual system performances with respect to one gold
      standard annotation set, available for the ShARe/CLEF corpus. Furthermore, we
      built a silver standard annotation set from the individual systems' output and
      assess the quality as well as the contribution of individual systems to the
      quality of the silver standard. Our results demonstrate that mainly the NCBO
      annotator and cTAKES contribute to the silver standard corpora (F1-measures in
      the range of 21% to 74%) and their quality (best F1-measure of 33%), independent
      from the type of text investigated. While BeCAS and MetaMap can contribute to the
      precision of silver standard annotations (precision of up to 42%), the F1-measure
      drops when combined with NCBO Annotator and cTAKES due to a low recall. In
      conclusion, the performances of individual systems need to be improved
      independently from the text types, and the leveraging strategies to best take
      advantage of individual systems' annotations need to be revised. The textual
      content of the PubMed corpus, accession numbers for the clinical trials corpus,
      and assigned annotations of the four concept recognition systems as well as the
      generated silver standard annotation sets are available from
      http://purl.org/phenotype/resources. The textual content of the ShARe/CLEF
      (https://sites.google.com/site/shareclefehealth/data) and i2b2
      (https://i2b2.org/NLP/DataSets/) corpora needs to be requested with the
      individual corpus providers. 

PMID- 25607984
TI  - Low Na, high K diet and the role of aldosterone in BK-mediated K excretion.
AB  - A low Na, high K diet (LNaHK) is associated with a low rate of cardiovascular
      (CV) disease in many societies. Part of the benefit of LNaHK relies on its
      diuretic effects; however, the role of aldosterone (aldo) in the diuresis is not
      understood. LNaHK mice exhibit an increase in renal K secretion that is dependent
      on the large, Ca-activated K channel, (BK-alpha with accessory BK-beta4; BK
      alpha/beta4). We hypothesized that aldo causes an osmotic diuresis by increasing
      BK-alpha/beta4-mediated K secretion in LNaHK mice. We found that the plasma aldo
      concentration (P[aldo]) was elevated by 10-fold in LNaHK mice compared with
      control diet (Con) mice. We subjected LNaHK mice to either sham surgery (sham),
      adrenalectomy (ADX) with low aldo replacement (ADX-LA), or ADX with high aldo
      replacement (ADX-HA). Compared to sham, the urinary flow, K excretion rate,
      transtubular K gradient (TTKG), and BK-alpha and BK-beta4 expressions, were
      decreased in ADX-LA, but not different in ADX-HA. BK-beta4 knockout (beta4KO) and
      WT mice exhibited similar K clearance and TTKG in the ADX-LA groups; however, in
      sham and ADX-HA, the K clearance and TTKG of beta4KO were less than WT. In
      response to amiloride treatment, the osmolar clearance was increased in WT Con,
      decreased in WT LNaHK, and unchanged in beta4KO LNaHK. These data show that the
      high P[aldo] of LNaHK mice is necessary to generate a high rate of BK-alpha/beta4
      mediated K secretion, which creates an osmotic diuresis that may contribute to a
      reduction in CV disease. 

PMID- 25607985
TI  - The phylogenetically-related pattern recognition receptors EFR and XA21 recruit
      similar immune signaling components in monocots and dicots.
AB  - During plant immunity, surface-localized pattern recognition receptors (PRRs)
      recognize pathogen-associated molecular patterns (PAMPs). The transfer of PRRs
      between plant species is a promising strategy for engineering broad-spectrum
      disease resistance. Thus, there is a great interest in understanding the
      mechanisms of PRR-mediated resistance across different plant species. Two well
      characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs)
      EFR and XA21 from Arabidopsis thaliana (Arabidopsis) and rice, respectively.
      Interestingly, despite being evolutionary distant, EFR and XA21 are
      phylogenetically closely related and are both members of the sub-family XII of
      LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of
      these related PRRs to engage immune signaling across the monocots-dicots
      taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show
      that the kinase domain of the rice XA21 is functional in triggering elf18-induced
      signaling and quantitative immunity to the bacteria Pseudomonas syringae pv.
      tomato (Pto) DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore,
      the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with
      known components of the EFR complex. Conversely, EFR associates with Arabidopsis
      orthologues of rice XA21-interacting proteins, which appear to be involved in EFR
      mediated signaling and immunity in Arabidopsis. Our work indicates the overall
      functional conservation of immune components acting downstream of distinct LRR-RK
      type PRRs between monocots and dicots. 

PMID- 25607986
TI  - Increase in ultrasonic intensity of blood speckle across moderate coronary artery
      stenosis is an independent predictor of functional coronary artery stenosis
      measured by fractional flow reserve: pilot study.
AB  - BACKGROUND AND AIMS: The degree of coronary artery stenosis should be assessed
      both anatomically and functionally. We observed that the intensity of blood
      speckle (IBS) on intravascular ultrasound (IVUS) is low proximal to a coronary
      artery stenosis, and high distal to the stenosis. We defined step-up IBS as the
      distal minus the proximal IBS, and speculated that this new parameter could be
      used for the functional evaluation of stenosis on IVUS. The aims of this study
      were to assess the relationships between step-up IBS and factors that affect
      coronary blood flow, and between step-up IBS and fractional flow reserve (FFR).
      METHODS AND RESULTS: This study enrolled 36 consecutive patients with angina who
      had a single moderate stenosis in the left anterior descending artery. All
      patients were evaluated by integrated backscatter IVUS and intracoronary pressure
      measurements. FFR was calculated from measurements using a coronary pressure wire
      during hyperemia. Conventional gray-scale IVUS images were recorded, and
      integrated backscatter was measured in three cross-sectional slices proximal and
      distal to the stenosis. Step-up IBS was calculated as (mean distal integrated
      backscatter value) - (mean proximal integrated backscatter value). Stepwise
      multiple linear regression analysis showed that the heart rate (r = 0.45, P =
      0.005), ejection fraction (r = -0.39, P = 0.01), and hemoglobin level (r = -0.32,
      P = 0.04) were independently correlated with step-up IBS, whereas proximal and
      distal IBS were not associated with these factors. There was a strong inverse
      correlation between step-up IBS and FFR (r = -0.84, P < 0.001), which remained
      significant on stepwise multiple linear regression analysis. CONCLUSIONS: The
      newly defined parameter of step-up IBS is potentially useful for the functional
      assessment of coronary artery stenosis.

PMID- 25607988
TI  - Correction: temporal and anatomical host resistance to chronic salmonella
      infection is quantitatively dictated by nramp1 and influenced by host genetic
      background.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0111763.]. 

PMID- 25607987
TI  - Catalysis by the tumor-suppressor enzymes PTEN and PTEN-L.
AB  - Phosphatase and tensin homologue deleted from chromosome ten (PTEN) is a lipid
      phosphatase tumor suppressor that is lost or inactivated in most human tumors.
      The enzyme catalyzes the hydrolysis of phosphatidylinositol-(3,4,5)-trisphosphate
      (PIP3) to form phosphatidylinositol-(4,5)-bisphosphate (PIP2) and inorganic
      phosphate. Here, we report on the first continuous assay for the catalytic
      activity of PTEN. Using this assay, we demonstrate that human PTEN is activated
      by the reaction product PIP2, as well as in solutions of low salt concentration.
      This activation is abrogated in the K13A variant, which has a disruption in a
      putative binding site for PIP2. We also demonstrate that PTEN-L, which derives
      from alternative translation of the PTEN mRNA, is activated constitutively. These
      findings have implications for catalysis by PTEN in physiological environments
      and could expedite the development of PTEN-based chemotherapeutic agents. 

PMID- 25607989
TI  - Tuning carbon nanotube assembly for flexible, strong and conductive films.
AB  - Carbon nanotubes are ideal scaffolds for designing and architecting flexible
      graphite films with tunable mechanical, electrical and thermal properties.
      Herein, we demonstrate that the assembly of aligned carbon nanotubes with
      different aggregation density and morphology leads to different mechanical
      properties and anisotropic electrical conduction along the films. Using drying
      evaporation under tension treatment, the carbon nanotubes can be assembled into
      strong films with tensile strength and Young's modulus as high as 3.2 GPa and 124
      GPa, respectively, leading to a remarkable toughness of 54.38 J g(-1), greatly
      outperforming conventional graphite films, spider webs and even Kevlar fiber
      films. Different types of solvents may result in the assembly of CNTs with
      different aggregation morphology and therefore different modulus. In addition, we
      reveal that the high density assembly of aligned CNTs correlates with better
      electric conduction along the axial direction, enabling these flexible graphite
      films to be both strong and conductive. 

PMID- 25607990
TI  - Association of INSIG2 polymorphism with overweight and LDL in children.
AB  - BACKGROUND: Dyslipidemia and overweight are common issues in children.
      Identifying genetic markers of risk could lead to targeted interventions. A
      polymorphism of SNP rs7566605 near insulin-induced gene 2 (INSIG2) has been
      identified as a strong candidate gene for obesity, through its feedback control
      of lipid synthesis. OBJECTIVE: To identify polymorphisms in INSIG2 which are
      associated with overweight (BMI >= 85% for age) and dyslipidemia in children.
      HYPOTHESIS: The C allele of rs7566605 would be significantly associated with BMI
      and LDL. DESIGN/METHODS: We genotyped 15 SNPs in/near INSIG2 in 1,058 healthy
      children (53% non-Hispanic white (NHW), 37% overweight) participating in a school
      based study. Genotype was compared with BMI and lipid markers, adjusting for age,
      gender, and puberty. RESULTS: We found a significant association between the SNP
      rs12464355 and LDL in NHW children, p < 0.001. The G allele is protective (lower
      LDL). A different SNP was associated with overweight in NHW: rs17047757. SNP
      rs7566605 was not associated with overweight or lipid levels. CONCLUSIONS: We
      identified novel genetic associations between INSIG2 and both overweight and LDL
      in NHW children. Polymorphisms in INSIG2 may be important in the development of
      obesity through its effects on lipid regulation.

PMID- 25607992
TI  - An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare
      cell populations.
AB  - Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq)
      has enabled genome-wide epigenetic profiling of numerous cell lines and tissue
      types. A major limitation of ChIP-seq, however, is the large number of cells
      required to generate high-quality data sets, precluding the study of rare cell
      populations. Here, we present an ultra-low-input micrococcal nuclease-based
      native ChIP (ULI-NChIP) and sequencing method to generate genome-wide histone
      mark profiles with high resolution from as few as 10(3) cells. We demonstrate
      that ULI-NChIP-seq generates high-quality maps of covalent histone marks from
      10(3) to 10(6) embryonic stem cells. Subsequently, we show that ULI-NChIP-seq
      H3K27me3 profiles generated from E13.5 primordial germ cells isolated from single
      male and female embryos show high similarity to recent data sets generated using
      50-180 * more material. Finally, we identify sexually dimorphic H3K27me3
      enrichment at specific genic promoters, thereby illustrating the utility of this
      method for generating high-quality and -complexity libraries from rare cell
      populations. 

PMID- 25607991
TI  - Comparative genomic and phylogenetic analyses of Gammaproteobacterial glg genes
      traced the origin of the Escherichia coli glycogen glgBXCAP operon to the last
      common ancestor of the sister orders Enterobacteriales and Pasteurellales.
AB  - Production of branched alpha-glucan, glycogen-like polymers is widely spread in
      the Bacteria domain. The glycogen pathway of synthesis and degradation has been
      fairly well characterized in the model enterobacterial species Escherichia coli
      (order Enterobacteriales, class Gammaproteobacteria), in which the cognate genes
      (branching enzyme glgB, debranching enzyme glgX, ADP-glucose pyrophosphorylase
      glgC, glycogen synthase glgA, and glycogen phosphorylase glgP) are clustered in a
      glgBXCAP operon arrangement. However, the evolutionary origin of this particular
      arrangement and of its constituent genes is unknown. Here, by using 265 complete
      gammaproteobacterial genomes we have carried out a comparative analysis of the
      presence, copy number and arrangement of glg genes in all lineages of the
      Gammaproteobacteria. These analyses revealed large variations in glg gene
      presence, copy number and arrangements among different gammaproteobacterial
      lineages. However, the glgBXCAP arrangement was remarkably conserved in all glg
      possessing species of the orders Enterobacteriales and Pasteurellales (the E/P
      group). Subsequent phylogenetic analyses of glg genes present in the
      Gammaproteobacteria and in other main bacterial groups indicated that glg genes
      have undergone a complex evolutionary history in which horizontal gene transfer
      may have played an important role. These analyses also revealed that the E/P
      glgBXCAP genes (a) share a common evolutionary origin, (b) were vertically
      transmitted within the E/P group, and (c) are closely related to glg genes of
      some phylogenetically distant betaproteobacterial species. The overall data
      allowed tracing the origin of the E. coli glgBXCAP operon to the last common
      ancestor of the E/P group, and also to uncover a likely glgBXCAP transfer event
      from the E/P group to particular lineages of the Betaproteobacteria. 

PMID- 25607993
TI  - Retaining Part D's comprehensive coverage of antidepressants: not a silver
      bullet.

PMID- 25607994
TI  - Unliganded thyroid hormone receptor function: amphibian metamorphosis got TALENs.

PMID- 25607997
TI  - Dissociative photoionization of quinoline and isoquinoline.
AB  - Two nitrogen-containing polycyclic aromatic hydrocarbon isomers of C9H7N
      composition, quinoline, and isoquinoline have been studied by imaging
      photoelectron photoion coincidence spectroscopy at the VUV beamline of the Swiss
      Light Source. High resolution threshold photoelectron spectra have been recorded
      and are interpreted applying a Franck-Condon model. Dissociative ionization mass
      spectra as a function of the parent ion internal energy are analyzed with the use
      of breakdown diagrams. HCN loss and H loss are the dominant dissociation paths
      for both C9H7N(*+) isomers at photon energies below 15.5 eV. Computed C9H7N(*+)
      potential energy surfaces suggest that the lowest energy path leading to HCN-loss
      yields the benzocyclobutadiene cation. A statistical model is used to fit the
      breakdown diagram and-to account for the kinetic shift-the time-of-flight mass
      spectra that reveal the dissociation rates. We have derived appearance energies
      of 11.9 +/- 0.1 (HCN loss) and 12.0 +/- 0.1 (H loss), as well as 11.6 +/- 0.2
      (HCN loss) and 12.1 +/- 0.2 (H loss) eV, for the dissociative ionization of
      quinoline and isoquinoline, respectively. The results are compared to a recent
      study on the dissociative ionization of naphthalene. Implications for the
      formation and destruction of nitrogenated PAHs in the interstellar medium and in
      Titan's atmosphere are highlighted. 

PMID- 25607999
TI  - Advocating Nonsurgical Management of Patients With Small, Incidental Radial Scars
      at the Time of Needle Core Biopsy: A Study of 77 Cases.
AB  - CONTEXT: Radial scars are benign sclerosing lesions that are routinely excised
      when diagnosed in a needle core biopsy. Optimal management for patients with
      incidental and small (<=5 mm) radial scars is uncertain. OBJECTIVE: To assess
      pathologic upgrade of radial scars diagnosed in needle core biopsy samples and
      identify a subset of patients who could benefit from conservative management.
      DESIGN: Patients with a diagnosis of radial scar in a needle core biopsy who
      underwent excision of the biopsied area were identified. Radial scars greater
      than 5 mm in size and those with coexisting atypia, carcinoma, and papillary
      lesions were excluded. After histologic-radiographic correlation, rates of
      pathologic upgrade were assessed. RESULTS: Seventy-seven radial scars diagnosed
      in 66 patients were included. Overall, 9 of 77 (12%) showed upgrade to a high
      risk lesion (6 lobular carcinoma in situ, 2 atypical ductal hyperplasia, 1
      atypical lobular hyperplasia), while none (0%) showed upgrade to invasive
      carcinoma or ductal carcinoma in situ. One of 22 incidental radial scars (4.5%)
      showed upgrade on excision versus 6 of 36 (16.7%) for radial scars considered to
      be the radiographic target (P = .23). Older age was associated with upgrade (P <
      .001). CONCLUSIONS: No incidental or small (<=5 mm) radial scars excised revealed
      invasive carcinoma or ductal carcinoma in situ on excision. Provided there is
      good pathologic-radiologic concordance, it appears reasonable for these patients
      to be managed conservatively.

PMID- 25607998
TI  - Plasma folate, vitamin B12, and homocysteine and cancers of the esophagus,
      stomach, and liver in a Chinese population.
AB  - Evidence is accumulating regarding a role of micronutrients in folate metabolism
      in cancer risk. We investigated the associations of plasma folate, vitamin B12,
      and homocysteine with upper gastrointestinal (GI) cancers in a population-based
      case-control study in Taixing City, China. With informed consent, we recruited
      cases with cancers of esophagus (n = 218), stomach (n = 206), and liver (n =
      204), and one common healthy control group (n = 405). A standardized
      epidemiologic questionnaire was used in face-to-face interviews, and blood
      samples were collected during interviews. We observed an inverse association
      between plasma folate levels and liver cancer. The adjusted odds ratio (aOR) was
      0.46 [95% confidence interval (CI) = 0.24-0.88] comparing individuals in the
      highest quartile to those in the lowest. We found a positive association between
      plasma vitamin B12 levels and all three cancers. The aORs for those in the
      highest quartile were 2.80 (95% CI = 1.51-5.18) for esophageal cancer, 2.17 (1.21
      3.89) for stomach cancer, and 9.97 (4.82-20.60) for liver cancer, comparing to
      those in the lowest quartile. We further observed interaction between plasma
      folate and vitamin B12 on these cancers. Our data indicated associations between
      plasma folate and vitamin B12 with upper GI cancers in Chinese population.
      Further research is warranted considering the debate over the necessity of food
      fortification. 

PMID- 25608000
TI  - Helical defects in microRNA influence protein binding by TAR RNA binding protein.
AB  - BACKGROUND: MicroRNAs (miRNAs) are critical post-transcriptional regulators of
      gene expression. Their precursors have a globally A-form helical geometry, which
      prevents most proteins from identifying their nucleotide sequence. This suggests
      the hypothesis that local structural features (e.g., bulges, internal loops) play
      a central role in specific double-stranded RNA (dsRNA) selection from cellular
      RNA pools by dsRNA binding domain (dsRBD) containing proteins. Furthermore, the
      processing enzymes in the miRNA maturation pathway require tandem-dsRBD cofactor
      proteins for optimal function, suggesting that dsRBDs play a key role in the
      molecular mechanism for precise positioning of the RNA within these multi-protein
      complexes. Here, we focus on the tandem-dsRBDs of TRBP, which have been shown to
      bind dsRNA tightly. METHODOLOGY/PRINCIPAL FINDINGS: We present a combination of
      dsRNA binding assays demonstrating that TRBP binds dsRNA in an RNA-length
      dependent manner. Moreover, circular dichroism data shows that the number of
      dsRBD moieties bound to RNA at saturation is different for a tandem-dsRBD
      construct than for constructs with only one dsRBD per polypeptide, revealing
      another reason for the selective pressure to maintain multiple domains within a
      polypeptide chain. Finally, we show that helical defects in precursor miRNA alter
      the apparent dsRNA size, demonstrating that imperfections in RNA structure
      influence the strength of TRBP binding. CONCLUSION/SIGNIFICANCE: We conclude that
      TRBP is responsible for recognizing structural imperfections in miRNA precursors,
      in the sense that TRBP is unable to bind imperfections efficiently and thus is
      positioned around them. We propose that once positioned around structural
      defects, TRBP assists Dicer and the rest of the RNA-induced silencing complex
      (RISC) in providing efficient and homogenous conversion of substrate precursor
      miRNA into mature miRNA downstream.

PMID- 25608001
TI  - Influence of levosimendan postconditioning on apoptosis of rat lung cells in a
      model of ischemia-reperfusion injury.
AB  - OBJECTIVE: To ascertain if levosimendan postconditioning can alleviate lung
      ischemia-reperfusion injury (LIRI) in rats. METHOD: One hundred rats were divided
      into five groups: Sham (sham), ischemia-reperfusion group (I/R group), ischemic
      postconditioning (IPO group), levosimendan postconditioning (Levo group) and
      combination postconditioning group of levosimendan and 5-Hydroxydecanoic acid
      (Levo+5-HD group). The apoptotic index (AI) of lung tissue cells was determined
      using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      assay. Expression of active cysteine aspartate specific protease-3 ( active
      caspase-3), Bcl-2 and Bax in lung tissue was determined by immunohistochemical
      staining. The morphopathology of lung tissue was observed using light and
      electron microscopy. RESULTS: AI values and expression of active caspase-3, Bcl-2
      and Bax of lung tissue in I/R and Levo+5-HD groups were significantly higher than
      those in the sham group ( P<0.05). AI values and expression of active caspase-3
      and Bax were significantly lower, whereas that of Bcl-2 was higher significantly
      in the Levo group, compared with I/R and Levo+5-HD groups (P<0.05). Significant
      differences were not observed in comparisons between I/R and Levo+5-HD groups as
      well as IPO and Levo groups. CONCLUSION: LIRI can be alleviated by levosimendan,
      which simulates an IPO protective function. A postulated lung-protective
      mechanism of action could involve opening of mitochondrial adenosine triphosphate
      sensitive potassium channels, relieving Ca2+ overload, upregulation of expression
      of Bcl-2, and downregulation of expression of active caspase-3 and Bax.

PMID- 25608002
TI  - Proteomic profiling reveals autoimmune targets in sarcoidosis.
AB  - RATIONALE: There is a need to further characterize the antibody repertoire in
      relation to sarcoidosis and potentially related autoantigens. OBJECTIVES: We
      investigated bronchoalveolar lavage (BAL) and serum samples from patients with
      sarcoidosis and healthy and diseased control subjects to discover sarcoidosis
      associated autoantigens. METHODS: Antigen microarrays built on 3,072 protein
      fragments were used to screen for IgG reactivity in 73 BAL samples from subjects
      with sarcoidosis, subjects with asthma, and healthy subjects. A set of 131
      targets were selected for subsequent verification on suspension bead arrays using
      272 additional BAL samples and 141 paired sera. Reactivity to four antigens was
      furthermore analyzed in 22 unprocessed BAL samples from patients with fibrosis
      and 269 plasma samples from patients diagnosed with myositis. MEASUREMENTS AND
      MAIN RESULTS: Reactivity toward zinc finger protein 688 and mitochondrial
      ribosomal protein L43 were discovered with higher frequencies in patients with
      sarcoidosis, for mitochondrial ribosomal protein L43 especially in patients with
      non-Lofgren syndrome. Increased reactivity toward nuclear receptor coactivator 2
      was also observed in patients with non-Lofgren syndrome as compared with patients
      with Lofgren syndrome. The antigen representing adenosine diphosphate
      ribosylation factor GTPase activating protein 1 revealed high reactivity
      frequency in all sample groups but with significantly higher level of IgG
      reactivities in patients with sarcoidosis. CONCLUSIONS: Autoantigen reactivity
      was present in most BAL and serum samples analyzed, and the results revealed high
      interindividual heterogeneity, with most of the reactivities observed in single
      individuals only. Four proteins are here proposed as sarcoidosis-associated
      autoimmune targets and of interest for further validation in independent cohorts.

PMID- 25608003
TI  - Risk estimation of HNA-3 incompatibility and alloimmunization in Thai
      populations.
AB  - Severe transfusion-related acute lung injury (TRALI) is often due to antibodies
      in blood components directed against human neutrophil antigen (HNA)-3a. This
      study aimed to report the genotype frequencies of the HNA-3 system and to
      estimate the potential risk of HNA-3 incompatibility and alloimmunization in two
      Thai populations. Eight hundred DNA samples obtained from 500 unrelated healthy
      blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok and
      300 samples from the Blood Bank, Faculty of Medicine, Chiang Mai University,
      Chiang Mai, Thailand were included. HNA-3 genotyping was performed using an in
      house polymerase chain reaction with sequence-specific primer (PCR-SSP)
      technique. The observed frequencies of the HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b
      genotypes were 0.528, 0.380, and 0.092 in central Thais and 0.600, 0.350, and
      0.050 in northern Thais, respectively. The frequencies were used to estimate HNA
      3 incompatibility and risk of HNA-3a alloimmunization. The HNA-3 incompatibility
      in central Thais (33.28%) was higher than northern Thais (28.75%), corresponding
      to a significantly higher probability of HNA-3a alloimmunization (P<0.05) similar
      to Japanese and Chinese populations. This study showed the high risk of HNA-3
      incompatibility and alloimmunization, especially in central Thai blood donors. A
      molecular-based identification of the HNA-3 genotype of female donors is
      suggested to reduce the risk of TRALI following plasma and whole blood allogeneic
      transfusion. 

PMID- 25608005
TI  - Northern-hemispheric differential warming is the key to understanding the
      discrepancies in the projected Sahel rainfall.
AB  - Future projections of the Sahel rainfall are highly uncertain, with different
      climate models showing widely differing rainfall trends. Moreover, the twentieth
      century cross-model consensus linking Sahel rainfall to tropical sea-surface
      temperatures (SSTs) is no longer applicable in the twenty-first century. Here we
      show that the diverse future Northern Hemisphere differential warming between
      extratropical and tropical SSTs can explain the discrepancy in the projected
      Sahel rainfall. The relationship between SST and Sahel rainfall that holds for
      the twentieth-century persists into the twenty-first century when the
      differential SST warming is taken into account. A suite of SST-sensitivity
      experiments confirms that strong Northern Hemisphere extratropical warming
      induces a significant increase in Sahel rainfall, which can predominate over the
      drying impact of tropical SST warming. These results indicate that a trustworthy
      projection of Sahel rainfall requires the estimation of the most likely future
      Northern-hemispheric differential warming. 

PMID- 25608004
TI  - Location of triple-negative breast cancers: comparison with estrogen receptor
      positive breast cancers on MR imaging.
AB  - There has been a major need to better understand the biological characteristics
      of triple-negative breast cancers. Compared with estrogen receptor (ER)-positive
      cancers, several magnetic resonance (MR) imaging findings have been reported as
      characteristic findings. However, information regarding their location has not
      been described. Our study was to compare the location of triple-negative breast
      cancers with that of ER-positive breast cancers using magnetic resonance (MR)
      imaging. The locations of 1102 primary breast cancers (256 triple-negative and
      846 ER-positive) in 1090 women (mean, 52.1 years) were reviewed using three
      dimensional (3D) coordinates. The x-axis measurement was recorded as the
      transverse distance from the posterior nipple line; y-axis measurement as the
      anteroposterior distance from the chest wall; z-axis measurement as the
      superoinferior distance from the posterior nipple line. The association between
      breast cancer subtype and tumor location was evaluated using multiple linear
      regression analysis. Triple-negative breast cancers were significantly closer to
      the chest wall than ER-positive breast cancers in absolute (1.8 cm vs. 2.3 cm, P
      < .0001) and normalized (0.21 vs. 0.25, P < .0001) y-axis distances. The x- and z
      axes distances were not significantly different between triple-negative and ER
      positive breast cancers. Multiple linear regression analysis revealed that age,
      mammographic density, axillary nodal status, and triple-negative subtype were
      significantly associated with absolute and normalized distances from the chest
      wall (all P < .05). Our results show that triple-negative breast cancers have a
      tendency toward a posterior or prepectoral location compared with ER-positive
      breast cancers. 

PMID- 25608006
TI  - Dynamic growth and shrinkage govern the pH dependence of RecA filament stability.
AB  - RecA proteins form a long stable filament on a single-stranded DNA and catalyze
      strand exchange reaction. The stability of RecA filament changes dramatically
      with pH, yet its detailed mechanism is not known. Here, using a single molecule
      assay, we determined the binding and dissociation rates of RecA monomers at the
      filament ends at various pH. The pH-induced rate changes were moderate but
      occurred in opposite directions for binding and dissociation, resulting in a
      substantial increase in filament stability in lower pH. The highly charged
      residues in C-terminal domain do not contribute to the pH dependent stability.
      The stability enhancement of RecA filament in low pH may help the cell to cope
      with acidic stress by fine-tuning of the binding and dissociation rates without
      losing the highly dynamic nature of the filament required for strand exchange. 

PMID- 25608007
TI  - Alternative carrier injection/extraction inspired by electrode interlayers based
      on peripheral modification of the electron-rich skeleton.
AB  - Peripheral modifications of the electron-rich trifluorene-substituted
      triphenylamine core have been comparatively studied through the linkage of the
      different polar pendants with fluorene via saturated sp3 hybrid alkyl chains. The
      work function of electrode could be effectively tuned by the interlayers with or
      without peripheral pendants of phosphoric acid and phosphonate groups to give
      selective hole and electron injection/extraction property. Their applications in
      various vacuum- and solution-processed organic light-emitting diodes and
      photovoltaic devices were thoroughly investigated. The current comparative study
      provides valuable exploration on developing high-performance environmentally
      friendly solvent-processed electrode interlayer materials.

PMID- 25608008
TI  - The ABCs of ICD.

PMID- 25608010
TI  - Don't let your revenue be part of the $4.9 billion returned to taxpayers!
AB  - Wound care professionals should carefully inspect and audit their coding and
      billing practices in light of (1) the OIG's 2014 Semiannual Report to Congress
      and (2) the 2015 OIG Work Plan.You can read the details of both documents by
      following the Internet links provided earlier in this article. Conducting those
      self-audits and taking steps to correct issues are far better than the possible
      alternatives, for example: exclusion from participating in Medicare, Medicaid,
      and other federal healthcare program civil monetary penalties for submitting or
      causing to be submitted a claim for items or services that the person knows or
      should know is false or fraudulent criminals penalties for the following:)
      knowingly and willfully soliciting, receiving, offering, or paying remuneration
      (in cash or in kind) to induce, or) in return for (1) referring an individual to
      a person or an entity for the furnishing, or arranging for the furnishing, of any
      item or service payable under the federal healthcare programs or (2) purchasing,
      leasing, or ordering, or arranging for or recommending the purchasing, leasing,
      or ordering, of any good,facility, service, or item payable under the federal
      healthcare programs.If wound care professionals identify problem areas during an
      audit, they should always contact their compliance officer.Together, they should
      decide if they should self-disclose to the OIG. Since 1998, the OIG has made
      available comprehensive guidelines describing the protocol for providers to
      voluntarily submit to OIG self-disclosures of fraud, waste, or abuse. The
      provider self-disclosure protocol gives providers an opportunity to minimize the
      potential costs and disruption that a full scale OIG audit or investigation might
      entail if fraud were uncovered. The self-disclosure also allows the provider to
      negotiate a fair monetary settlement and potentially avoid being excluded from
      participation in federal healthcare programs.The self-disclosure protocol guides
      providers and suppliers through the process of structuring a disclosure to OIG
      about matters that constitute potential violations of federal laws. After making
      an initial disclosure, the provider or supplier is expected to thoroughly
      investigate the nature and cause of the matters uncovered and make a reliable
      assessment of their economic impact. The OIG evaluates the reported results of
      each internal investigation to determine the appropriate course of action. The
      self-disclosure guidelines are available on the OIG website at
      http://oig.hhs.gov/compliance/self-disclosure-info.

PMID- 25608011
TI  - Use of silicone materials to simulate tissue biomechanics as related to deep
      tissue injury.
AB  - OBJECTIVE: Deep tissue injury (DTI) is caused by prolonged mechanical loading
      that disrupts blood flow and metabolic clearance. A patient simulator that mimics
      the biomechanical aspects of DTI initiation, stress and strain in deep muscle
      tissue, would be potentially useful as a training tool for pressure-relief
      techniques and testing platform for pressure-mitigating products. As a step
      toward this goal, this study evaluates the ability of silicone materials to mimic
      the distribution of stress in muscle tissue under concentrated loading. METHODS:
      To quantify the mechanical properties of candidate silicone materials, unconfined
      compression experiments were conducted on 3 silicone formulations (Ecoflex 0030,
      Ecoflex 0010, and Dragon Skin; Smooth-On, Inc, Easton, Pennsylvania). Results
      were fit to an Ogden hyperelastic material model, and the resulting shear moduli
      (G) were compared with published values for biological tissues. Indentation tests
      were then conducted on Ecoflex 0030 and porcine muscle to investigate silicone's
      ability to mimic the nonuniform stress distribution muscle demonstrates under
      concentrated loading. Finite element models were created to quantify stresses
      throughout tissue depth. Finally, a preliminary patient simulator prototype was
      constructed, and both deep and superficial "tissue" pressures were recorded to
      examine stress distribution. RESULTS: Indentation tests showed similar stress
      distribution trends in muscle and Ecoflex 0030, but stress magnitudes were higher
      in Ecoflex 0030 than in porcine muscle. All 3 silicone formulations demonstrated
      shear moduli within the range of published values for biological tissue. For the
      experimental conditions reported in this work, Ecoflex 0030 exhibited greater
      stiffness than porcine muscle. CONCLUSION: Indentation tests and the prototype
      patient simulator trial demonstrated similar trends with high pressures closest
      to the bony prominence with decreasing magnitude toward the interfacial surface.
      Qualitatively, silicone mimicked the phenomenon observed in muscle of nonuniform
      stress under concentrated loading. Although shear moduli were within biological
      ranges, stress and stiffness values exceeded those of porcine muscle. This
      research represents a first step toward development of a preclinical model
      simulating the biomechanical conditions of stress and strain in deep muscle,
      since local biomechanical factors are acknowledged to play a role in DTI
      initiation. Future research is needed to refine the capacity of preclinical
      models to simulate biomechanical parameters in successive tissue layers of
      muscle, fat, dermis, and epidermis typically intervening between bone and support
      surfaces, for body regions at risk for DTI.

PMID- 25608013
TI  - Association of sociodemographic factors with hope for cure, religiosity, and
      spirituality in patients with venous ulcers.
AB  - OBJECTIVE: The objective of the study was to evaluate the association of
      sociodemographic factors with hope for cure and levels of religiosity and
      spirituality in patients with venous leg ulcers (VLUs). DESIGN: This was a
      primary, prospective, descriptive, analytical, clinical, nonrandomized study.
      SETTING: The study was performed at a nursing care and education center of a
      university hospital in interior Minas Gerais, Brazil. PATIENTS: A convenience
      sample of 50 adult patients with VLUs and Doppler ankle-brachial index ranging
      from 0.8 to 1.0 participated in the study. Patients with mixed ulcers, arterial
      ulcers, and diabetic foot ulcers were excluded from the study. MAIN OUTCOME
      MEASURES: A questionnaire assessing sociodemographic and clinical characteristics
      of patients, the Spirituality Self-rating Scale (SSRS), and the Herth Hope Index
      (HHI) were administered to all patients. MAIN RESULTS: The mean SSRS score was
      10.20, and the mean HHI was 25.5, corresponding to low levels of spirituality and
      moderate hope for cure, respectively. Patients aged between 50 and 59 years, men,
      nonsmokers, and those who were unemployed had the lowest mean SSRS scores. The
      lowest mean HHI values were reported by patients whose ulcers had exudate and
      odor, those aged 20 to 39 years, retired, and living with the wound for 1 year or
      less. Patients who had no religion or were not practicing a religion and those
      who considered living with an ulcer as a punishment reported low SSRS scores.
      CONCLUSION: The results showed that most patients with VLUs had low levels of
      spirituality, did not perceive divine intervention in their daily life or
      practice religious activities such as prayer, and had moderate hope for cure.

PMID- 25608012
TI  - What is the healing time of Stage II pressure ulcers? Findings from a secondary
      analysis.
AB  - Pressure ulcers (PrUs) remain a concern for clinicians, patients, caregivers, and
      researchers. Although data on prevalence and incidence are available, as well as
      evidence-based prevention and management intervention, PrU healing time is
      underreported. OBJECTIVE: The objective of this study was to evaluate the healing
      time of Stage II PrUs. METHODS: Secondary analysis of data collected from a
      multicenter randomized clinical trial was undertaken. Patients (a) with a Stage
      II PrU, (b) older than 18 years, and (c) who had given informed consent were
      included. The endpoints of the study were complete re-epithelialization of the
      PrU measured with the Pressure Ulcer Scale for Healing Tool 3.0 and the healing
      time. A network of 46 healthcare centers located in northern Italy participated
      in the study. RESULTS: Two hundred seventy patients with an average age of 83.9
      years (95% confidence interval [CI], 82.71-85.10) were recruited. Among 270 Stage
      II PrUs included, 153 lesions healed (56.7%), whereas 74 (27.4%) were still
      present after 10 weeks of follow-up. For 43 lesions (15.9%), the follow-up
      evaluation was interrupted because of patient death or transfer to units not
      included in the study. The PrUs healed on an average of 22.9 days (95% CI, 20.47
      25.37 days), with a median of 18 days. The average healing time for PrUs of less
      than 3.1 cm was significantly shorter (19.2 days; 95% CI, 16.6-21.8) compared
      with those 3.1 cm or greater (31.0 days; 95% CI, 26.4-35.6 days) (P = .000).
      CONCLUSIONS: To achieve complete re-epithelialization in Stage II PrUs, it takes
      approximately 23 days. This is quite a long time if we consider that pressures of
      only 60 to 70 mm Hg for between 30 and 240 minutes are needed to cause tissue
      damage. On average, a small ulcer heals 12 days faster compared with those with a
      surface of 3.1 cm or greater.

PMID- 25608014
TI  - Changes in classifications of chronic lower-limb wound codes in patients with
      diabetes: ICD-9-CM versus ICD-10-CM.
AB  - PURPOSE: To enhance the learner's competence with knowledge of changes in
      classifications of chronic lower limb wound codes from ICD-9-CM to ICD-10-CM in
      patients with diabetes. TARGET AUDIENCE: This continuing education activity is
      intended for physicians and nurses with an interest in skin and wound care.
      OBJECTIVES: After participating in this educational activity, the participant
      should be better able to:1. Identify the upcoming transition date and coding
      differences of ICD-9-CM and ICD-10-CM coding.2. Interpret the author's study
      population, methods, and design.3. Summarize the author's study findings
      comparing ICD-9-CM coding to ICD-10-CM coding. ABSTRACT:  OBJECTIVE: To determine
      the sensitivity and specificity of International Classification of Diseases,
      Ninth Edition, Clinical Modification (ICD-9-CM) and ICD-10-CM codes for
      individuals with diabetes and foot ulcers. DESIGN AND METHODS: Wound care
      providers and researchers are concerned about the potential impacts when the
      United States transitions from ICD-9-CM to ICD-10-CM. To identify the impact on
      diabetic foot ulcers, health history and wound variables were prospectively
      assessed with criterion-standard data from a prospective study of 49 patients
      with 65 foot ulcer episodes representing 81 incident foot ulcers. The ICD-9-CM
      and ICD-10-CM code sets were mapped to correctly classify individuals with
      diabetes and foot ulcers. RESULTS: Frequencies for health history variables were
      similar in both systems. The ICD-9 code did not capture any data on laterality
      (left or right) or ulcer depth/severity. The ICD-9 captured 69 of 81 incident
      ulcers (85%) and 94% of heel and midfoot ulcers, whereas the ICD-10 code captured
      78 of 81 incident ulcers (96%) and all incident heel or midfoot ulcers.
      Sensitivity and specificity for ulcer characteristics were consistently lower in
      ICD-9 than in ICD-10. CONCLUSIONS: The ICD-9 and ICD-10 are similar for data
      capture on health history variables, but wound variables are captured more
      accurately using ICD-10. The increased specificity of ICD-10 for ulcer location
      and severity improves identification and tracking ulcers during an episode of
      care.

PMID- 25608016
TI  - Tracking, monitoring, and measuring for process improvement.

PMID- 25608017
TI  - Regeneration of degenerated urinary sphincter muscles: improved stem cell-based
      therapies and novel imaging technologies.
AB  - Stress urinary incontinence (SUI) is a largely ousted but significant medical,
      social, and economic problem. Surveys suggest that nowadays approximately 10% of
      the male and 15% of the female population suffer from urinary incontinence at
      some stage in their lifetime. In women, two major etiologies contribute to SUI:
      degeneration of the urethral sphincter muscle controlling the closing mechanism
      of the bladder outflow and changes in lower pelvic organ position associated with
      degeneration of connective tissue or with mechanical stress, including obesity
      and load and tissue injury during pregnancy and delivery. In males, the reduction
      of the sphincter muscle function is sometimes due to surgical interventions as a
      consequence of prostate cancer treatment, benign prostate hyperplasia, or of
      neuropathical origin. Accordingly, for women and men different therapies were
      developed. In some cases, SUI can be treated by physical exercise,
      electrophysiological stimulation, and pharmacological interventions. If this
      fails to improve the situation, surgical interventions are required. In standard
      procedures, endoprostheses for mechanical support of the weakened tissue or
      mechanical valves for a bladder outflow control are implanted. In 20% of cases
      treated, repeat procedures are required as implants yield all sorts of side
      effects in time. Based on preclinical studies, the application of an advanced
      therapy medicinal product (ATMP) such as implantation of autologous cells may be
      a curative and long-lasting therapy for SUI. Cellular therapy could also be an
      option for men suffering from incontinence caused by injury of the nerves
      controlling the muscular sphincter system. Here we briefly report on human
      progenitor cells, especially on mesenchymal stromal cells (MSCs), their expansion
      and differentiation to smooth muscle or striated muscle cells in vitro, labeling
      of cells for in vivo imaging, concepts of improved, precise, yet gentle
      application of cells in muscle tissue, and monitoring of injected cells in situ. 

PMID- 25608018
TI  - Relationship satisfaction reduces the risk of maternal infectious diseases in
      pregnancy: the Norwegian Mother and Child Cohort Study.
AB  - OBJECTIVES: The aims of this study were to explore the degree to which
      relationship satisfaction predicts the risk of infectious diseases during
      pregnancy and to examine whether relationship satisfaction moderates the
      association between stressful life events and the risk of infections. METHODS:
      This was a prospective study based on data from the Norwegian Mother and Child
      Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health.
      Pregnant women (n = 67,244) completed questionnaires concerning relationship
      satisfaction and nine different categories of infectious diseases as well as
      socioeconomic characteristics and stressful life events. Associations between the
      predictor variables and the infectious diseases were assessed by logistic
      regression analyses. A multiple regression analysis was performed to assess a
      possible interaction of relationship satisfaction with stressful life events on
      the risk for infectious diseases. RESULTS: After controlling for marital status,
      age, education, income, and stressful life events, high levels of relationship
      satisfaction at week 15 of gestation were found to predict a significantly lower
      risk for eight categories of infectious diseases at gestational weeks 17-30. No
      significant interaction effect was found between relationship satisfaction and
      stressful life events on the risk for infections.

PMID- 25608020
TI  - Cell penetrating synthetic antimicrobial peptides (SAMPs) exhibiting potent and
      selective killing of mycobacterium by targeting its DNA.
AB  - Naturally occurring antimicrobial peptides (AMPs) are powerful defence tools to
      tackle pathogenic microbes. However, limited natural production and high
      synthetic costs in addition to poor selectivity limit large-scale use of AMPs in
      clinical settings. Here, we present a series of synthetic AMPs (SAMPs) that
      exhibit highly selective and potent killing of Mycobacterium (minimum inhibitory
      concentration <20 MUg mL(-1)) over E. coli or mammalian cells. These SAMPs are
      active against rapidly multiplying as well as growth saturated Mycobacterium
      cultures. These SAMPs are not membrane-lytic in nature, and are readily
      internalized by Mycobacterium and mammalian cells; whereas in E. coli, the
      lipopolysaccharide layer inhibits their cellular uptake, and hence, their
      antibacterial action. Upon internalization, these SAMPs interact with the
      unprotected genomic DNA of mycobacteria, and impede DNA-dependent processes,
      leading to bacterial cell death.

PMID- 25608021
TI  - Antiangiogenic-Like Properties of Fermented Extracts of Ayurvedic Medicinal
      Plants.
AB  - The three ayurvedic medicinal plants, Withania somnifera, Emblica officinalis,
      and Bacopa monnieri, were extracted by high-pressure static extraction using the
      Zippertex((r)) technology. The extracts were mixed to reach quantifiable amounts
      of active compounds identified by high-pressure liquid chromatography-mass
      spectrometry (HPLC-MS) analysis. The mixture of extracts was incubated with
      resting cells of the fungus Beauveria bassiana ATCC 7159. The fermentation
      promoted the fluidization of the starting dense mixture, while HPLC monitoring
      evidenced the disappearance of glucogallin from E. officinalis extract and the
      concomitant increase in gallic acid content. Topical exposure of the chick embryo
      chorioallantoic membrane (CAM) to the nonfermented extract led to the extensive
      necrosis and destruction of the treated membrane. However, the fermented extract
      was shown to be free of any toxicity. Furthermore, compared with the untreated
      CAM, the fermented sample reduced CAM vascularization, suggesting its
      antiangiogenic potency. The innocuity of the fermented extract was demonstrated
      using the in vivo LD50 test, the morphological examination of internal organs of
      treated rats, as well as the evaluation of blood biomarkers of liver damage
      (aspartate aminotransferase and alanine aminotransferase). The fermented extract
      was developed as a nutraceutical antiangiogenic treatment of age-related macular
      degeneration and commercialized in an oral form named Ethnodyne-VisioTM. 

PMID- 25608022
TI  - Correction: Separate Introns Gained within Short and Long Soluble Peridinin
      Chlorophyll a-Protein Genes during Radiation of Symbiodinium (Dinophyceae) Clade
      A and B Lineages.

PMID- 25608024
TI  - A cyclodiphosphazane based pincer ligand, [2,6-{MU-((t)BuN)2P((t)BuHN)PO}2C6H3I]:
      Ni(II), Pd(II), Pt(II) and Cu(I) complexes and catalytic studies.
AB  - Synthesis and late-transition metal complexes of pincer capable
      cyclodiphosphazane, 2,6-{MU-((t)BuN)2P((t)BuHN)PO}2C6H3I (1) are described. The
      condensation of 2-iodoresorcinol with cis-{ClP(MU-N(t)Bu)2PN(H)(t)Bu} produced a
      difunctional derivative 1 in good yield. The treatment of Ni(COD)2,
      Pd2(dba)3.CHCl3 or Pt(PPh3)4 with 1 afforded pincer complexes [2,6-{MU
      ((t)BuN)2P((t)BuHN)PO}2C6H3MI] (2 M = Ni; 3 M = Pd and 4 M = Pt). The reaction of
      complex 3 with copper halides resulted in the formation of heterobimetallic
      complexes bridged by rhombic {Cu(MU-X)}2 units, [{{Cu(MU-X)}2}{MU
      ((t)BuN)2P((t)BuHN)PO}2C6H3PdI] (5 X = I and 6 X = Br). The crystal structures of
      1-3, and 6 were established by single X-ray diffraction studies. The palladium
      complex 3 was tested for catalytic P-arylation of diphenylphosphine oxide
      (Ph2P(O)H) under microwave irradiation. Moderate to good catalytic activity was
      observed with aryl bromides.

PMID- 25608023
TI  - Neurophysiological effects of sleep deprivation in healthy adults, a pilot study.
AB  - Total sleep deprivation (TSD) may induce fatigue, neurocognitive slowing and mood
      changes, which are partly compensated by stress regulating brain systems,
      resulting in altered dopamine and cortisol levels in order to stay awake if
      needed. These systems, however, have never been studied in concert. At baseline,
      after a regular night of sleep, and the next morning after TSD, 12 healthy
      subjects performed a semantic affective classification functional magnetic
      resonance imaging (fMRI) task, followed by a [11C]raclopride positron emission
      tomography (PET) scan. Saliva cortisol levels were acquired at 7 time points
      during both days. Affective symptoms were measured using Beck Depression
      Inventory (BDI), Spielberger State Trait Anxiety Index (STAI) and visual analogue
      scales. After TSD, perceived energy levels, concentration, and speed of thought
      decreased significantly, whereas mood did not. During fMRI, response speed
      decreased for neutral words and positive targets, and accuracy decreased
      trendwise for neutral words and for positive targets with a negative distracter.
      Following TSD, processing of positive words was associated with increased left
      dorsolateral prefrontal activation. Processing of emotional words in general was
      associated with increased insular activity, whereas contrasting positive vs.
      negative words showed subthreshold increased activation in the (para)hippocampal
      area. Cortisol secretion was significantly lower after TSD. Decreased voxel-by
      voxel [11C]raclopride binding potential (BPND) was observed in left caudate. TSD
      induces widespread cognitive, neurophysiologic and endocrine changes in healthy
      adults, characterized by reduced cognitive functioning, despite increased
      regional brain activity. The blunted HPA-axis response together with altered
      [11C]raclopride binding in the basal ganglia indicate that sustained wakefulness
      requires involvement of additional adaptive biological systems. 

PMID- 25608025
TI  - Pluronic copolymer encapsulated SCR7 as a potential anticancer agent.
AB  - Nonhomologous end joining (NHEJ) of DNA double strand breaks (DSBs) inside cells
      can be selectively inhibited by 5,6-bis-(benzylideneamino)-2-mercaptopyrimidin-4
      ol (SCR7) which possesses anticancer properties. The hydrophobicity of SCR7
      decreases its bioavailability which is a major setback in the utilization of this
      compound as a therapeutic agent. In order to circumvent the drawback of SCR7, we
      prepared a polymer encapsulated form of SCR7. The physical interaction of SCR7
      and Pluronic(r) copolymer is evident from different analytical techniques. The in
      vitro cytotoxicity of the drug formulations is established using the MTT assay. 

PMID- 25608027
TI  - Eddy covariance flux measurements of gaseous elemental mercury using cavity ring
      down spectroscopy.
AB  - A newly developed pulsed cavity ring-down spectroscopy (CRDS) system for
      measuring atmospheric gaseous elemental mercury (GEM) concentrations at high
      temporal resolution (25 Hz) was used to successfully conduct the first eddy
      covariance (EC) flux measurements of GEM. GEM is the main gaseous atmospheric
      form, and quantification of bidirectional exchange between the Earth's surface
      and the atmosphere is important because gas exchange is important on a global
      scale. For example, surface GEM emissions from natural sources, legacy emissions,
      and re-emission of previously deposited anthropogenic pollution may exceed direct
      primary anthropogenic emissions. Using the EC technique for flux measurements
      requires subsecond measurements, which so far has not been feasible because of
      the slow time response of available instrumentation. The CRDS system measured GEM
      fluxes, which were compared to fluxes measured with the modified Bowen ratio
      (MBR) and a dynamic flux chamber (DFC). Measurements took place near Reno, NV, in
      September and October 2012 encompassing natural, low-mercury (Hg) background
      soils and Hg-enriched soils. During nine days of measurements with deployment of
      Hg-enriched soil in boxes within 60 m upwind of the EC tower, the covariance of
      GEM concentration and vertical wind speed was measured, showing that EC fluxes
      over an Hg-enriched area were detectable. During three separate days of flux
      measurements over background soils (without Hg-enriched soils), no covariance was
      detected, indicating fluxes below the detection limit. When fluxes were
      measurable, they strongly correlated with wind direction; the highest fluxes
      occurred when winds originated from the Hg-enriched area. Comparisons among the
      three methods showed good agreement in direction (e.g., emission or deposition)
      and magnitude, especially when measured fluxes originated within the Hg-enriched
      soil area. EC fluxes averaged 849 ng m(-2) h(-1), compared to DFC fluxes of 1105
      ng m(-2) h(-1) and MBR fluxes of 1309 ng m(-2) h(-1). This study demonstrated
      that a CRDS system can be used to measure GEM fluxes over Hg-enriched areas, with
      a conservative detection limit estimate of 32 ng m(-2) h(-1). 

PMID- 25608026
TI  - Global estimates of prevalent and incident herpes simplex virus type 2 infections
      in 2012.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection causes significant
      disease globally. Adolescent and adult infection may present as painful genital
      ulcers. Neonatal infection has high morbidity and mortality. Additionally, HSV-2
      likely contributes substantially to the spread of HIV infection. The global
      burden of HSV-2 infection was last estimated for 2003. Here we present new global
      estimates for 2012 of the burden of prevalent (existing) and incident (new) HSV-2
      infection among females and males aged 15-49 years, using updated methodology to
      adjust for test performance and estimate by World Health Organization (WHO)
      region. METHODS AND FINDINGS: We conducted a literature review of HSV-2
      prevalence studies world-wide since 2000. We then fitted a model with constant
      HSV-2 incidence by age to pooled HSV-2 prevalence values by age and sex.
      Prevalence values were adjusted for test sensitivity and specificity. The model
      estimated prevalence and incidence by sex for each WHO region to obtain global
      burden estimates. Uncertainty bounds were computed by refitting the model to
      reflect the variation in the underlying prevalence data. In 2012, we estimate
      that there were 417 million people aged 15-49 years (range: 274-678 million)
      living with HSV-2 infection world-wide (11.3% global prevalence), of whom 267
      million were women. We also estimate that in 2012, 19.2 million (range: 13.0-28.6
      million) individuals aged 15-49 years were newly-infected (0.5% of all
      individuals globally). The highest burden was in Africa. However, despite lower
      prevalence, South-East Asia and Western Pacific regions also contributed large
      numbers to the global totals because of large population sizes. CONCLUSIONS: The
      global burden of HSV-2 infection is large, leaving over 400 million people at
      increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV
      2 to partners or neonates. These estimates highlight the critical need for
      development of vaccines, microbicides, and other new HSV prevention strategies.

PMID- 25608028
TI  - Cysteine-specific Cu2+ chelating tags used as paramagnetic probes in double
      electron electron resonance.
AB  - Double electron electron resonance (DEER) is an attractive technique that is
      utilized for gaining insight into protein structure and dynamics via nanometer
      scale distance measurements. The most commonly used paramagnetic tag in these
      measurements is a nitroxide spin label, R1. Here, we present the application of
      two types of high-affinity Cu(2+) chelating tags, based on the EDTA and cyclen
      metal-binding motifs as alternative X-band DEER probes, using the B1
      immunoglobulin-binding domain of protein G (GB1) as a model system. Both types of
      tags have been incorporated into a variety of protein secondary structure
      environments and exhibit high spectral sensitivity. In particular, the cyclen
      based tag displays distance distributions with comparable distribution widths and
      most probable distances within 1-3 A when compared to homologous R1
      distributions. The results display the viability of the cyclen tag as an
      alternative to the R1 side chain for X-band DEER distance measurements in
      proteins. 

PMID- 25608030
TI  - Neonatal bowel obstruction with unilateral labial swelling. Diagnosis: Ovarian
      cyst with torsion.

PMID- 25608029
TI  - Whole-exome sequencing identifies somatic ATRX mutations in pheochromocytomas and
      paragangliomas.
AB  - Pheochromocytomas and paragangliomas (PCC/PGL) are the solid tumour type most
      commonly associated with an inherited susceptibility syndrome. However, very
      little is known about the somatic genetic changes leading to tumorigenesis or
      malignant transformation. Here we perform whole-exome sequencing on a discovery
      set of 21 PCC/PGL and identify somatic ATRX mutations in two SDHB-associated
      tumours. Targeted sequencing of a separate validation set of 103 PCC/PGL
      identifies somatic ATRX mutations in 12.6% of PCC/PGL. PCC/PGL with somatic ATRX
      mutations are associated with alternative lengthening of telomeres and clinically
      aggressive behaviour. This finding suggests that loss of ATRX, an SWI/SNF
      chromatin remodelling protein, is important in the development of clinically
      aggressive PCC/PGL. 

PMID- 25608031
TI  - Changes of field incurred chlorpyrifos and its toxic metabolite residues in rice
      during food processing from-RAC-to-consumption.
AB  - The objectives of this study were to determine the effects of food processing on
      field incurred residues levels of chlorpyrifos and its metabolite 3,5,6-Trichloro
      2-pyridinol (TCP) in rice. The chlorpyrifos and TCP were found to be 1.27 and
      0.093 mg kg-1 in straw and 0.41 and 0.073 mg kg-1 in grain, respectively. It is
      observed that the sunlight for 2 hours does not decrease the chlorpyrifos and TCP
      residues in grain significantly. Their residues in rice were reduced by up to 50%
      by hulling. The cooking reduced the chlorpyrifos and TCP in rice to undetectable
      level (below 0.01 mg kg-1). Processing factors (PFs) of chlorpyrifos and TCP
      residues in rice during food processing were similar. Various factors have
      impacts on the fates of chlorpyrifos and TCP residues and the important steps to
      reduce their residues in rice were hulling and cooking. The results can
      contribute to assure the consumer of a safe wholesome food supply. 

PMID- 25608032
TI  - Empathy, but not mimicry restriction, influences the recognition of change in
      emotional facial expressions.
AB  - The current study addressed the hypothesis that empathy and the restriction of
      facial muscles of observers can influence recognition of emotional facial
      expressions. A sample of 74 participants recognized the subjective onset of
      emotional facial expressions (anger, disgust, fear, happiness, sadness, surprise,
      and neutral) in a series of morphed face photographs showing a gradual change
      (frame by frame) from one expression to another. The high-empathy (as measured by
      the Empathy Quotient) participants recognized emotional facial expressions at
      earlier photographs from the series than did low-empathy ones, but there was no
      difference in the exploration time. Restriction of facial muscles of observers
      (with plasters and a stick in mouth) did not influence the responses. We discuss
      these findings in the context of the embodied simulation theory and previous data
      on empathy. 

PMID- 25608033
TI  - The state of population health surveillance using electronic health records: a
      narrative review.
AB  - Electronic health records (EHRs) are transforming the practice of clinical
      medicine, but the extent to which they are being harnessed to advance public
      health goals remains uncertain. Data extracted from integrated EHR networks offer
      the potential for almost real-time determination of the health status of
      populations in care, for targeting interventions to vulnerable populations, and
      for monitoring the impact of such initiatives over time. This is especially true
      in ambulatory care settings, which are uniquely suited for monitoring population
      health indicators including risk factors and disease management indicators
      associated with chronic diseases. As efforts gather steam to integrate health
      data across delivery systems, large networks of electronic patient information
      are increasingly emerging. Few of the national population health surveillance
      systems that rely on EHR data have progressed beyond laying groundwork to launch
      and maintain EHR-based surveillance, but a limited number of more focused or
      local efforts have demonstrated innovation in population health surveillance.
      Common challenges include incompleteness of population coverage, lack of
      interoperability across data systems, and variable data quality. This review
      defines progress, opportunities, and challenges in using EHR data for population
      health surveillance.

PMID- 25608034
TI  - Pepsinogens and pepsins from largemouth bass, Micropterus salmoides: purification
      and characterization with special reference to high proteolytic activities of
      bass enzymes.
AB  - Six pepsinogens were purified from the gastric mucosa of largemouth bass
      (Micropterus salmoides) by DEAE-Sephacel chromatography, Sephadex G-100 gel
      filtration, and Mono Q FPLC. The potential specific activities of two major
      pepsinogens, PG1-1 and PG2-2, against hemoglobin were 51 and 118 units/mg
      protein, respectively. The activity of pepsin 2-2 was the highest among the
      pepsins reported to date; this might be linked to the strongly carnivorous diet
      of the largemouth bass. The molecular masses of PG1-1 and PG2-2 were 39.0 and
      41.0 kDa, respectively. The N-terminal amino acid sequences of PG1-1 and PG2-2
      were LVQVPLEVGQTAREYLE- and LVRLPLIVGKTARQALLE-, respectively, showing
      similarities with those of fish type-A pepsinogens. The optimal pHs for
      hemoglobin-digestive activity of pepsins 1-1 and 2-2 were around 1.5 and 2.0,
      respectively, though both pepsins retained considerable activity at pHs over 3.5.
      They showed maximal activity around 50 and 40  degrees C, respectively. They were
      inhibited by pepstatin similarly to porcine pepsin A. The cleavage specificities
      clarified with oxidized insulin B chain were shown to be restricted to a few
      bonds consisting of hydrophobic/aromatic residues, such as the Leu(15)-Tyr(16),
      Phe(24)-Phe(25) and Phe(25)-Tyr(26) bonds. When hemoglobin was used as a
      substrate, the kcat/Km value of bass pepsin 2-2 was 4.6- to 36.8-fold larger than
      those of other fish pepsins. In the case of substance P, an ideal pepsin
      substrate mimic, the kcat/Km values were about 200-fold larger than those of
      porcine pepsin A, supporting the high activity of the bass pepsin.

PMID- 25608035
TI  - Pentafluoro-oxotellurate(VI) anions of mercury(II); syntheses and structures of
      [Hg(OTeF5)4](2-), [Hg(OTeF5)5](3-), [Hg2(OTeF5)6](2-), [Hg(OTeF5)4](2
      ).Hg(OTeF5)2, and [Hg2(OTeF5)7](3-).Hg(OTeF5)2.
AB  - Mercury(II) anions derived from the F5TeO- (teflate) group were synthesized and
      structurally characterized. The salts, [N(CH2CH3)4]2[Hg(OTeF5)4],
      [N(CH3)4]3[Hg(OTeF5)5], [N(CH2CH3)4]3[Hg(OTeF5)5], [N(CH3)4]2[Hg2(OTeF5)6],
      Cs2[Hg(OTeF5)4].Hg(OTeF5)2, and {Cs3[Hg2(OTeF5)7].Hg(OTeF5)2}.4SO2ClF, were
      obtained by reaction of Hg(OTeF5)2 with [M][OTeF5] (M = [N(CH3)4](+),
      [N(CH2CH3)4](+), Cs(+)) and were characterized by low-temperature single-crystal
      X-ray diffraction and low-temperature Raman spectroscopy. Unlike in the
      extensively fluorine-bridged solid-state structures of [HgF3](-) and [HgF4](2-),
      the less basic and more sterically demanding teflate ligands of the Hg(II) anions
      show less tendency to bridge. The anions exhibit a variety of structural motifs,
      ranging from well-isolated tetrahedral [Hg(OTeF5)4](2-) and square-pyramidal
      [Hg(OTeF5)5](3-) to the chain structures, [Hg2(OTeF5)6](2-) and [Hg2(OTeF5)7](3
      ).Hg(OTeF5)2. The geometrical parameters and vibrational frequencies of
      [Hg(OTeF5)4](2-) (S4), [Hg(OTeF5)5](3-) (C1), and [Hg2(OTeF5)6](2-) (D2) anions,
      as well as the hypothetical [Hg3(OTeF5)8](2-) (C1) anion, were calculated using
      density functional theory methods (PBE1PBE/def2-TZVPP), which aided in the
      assignment of the Raman spectra of [Hg(OTeF5)4](2-), [Hg(OTeF5)5](3-),
      [Hg2(OTeF5)6](2-), and Cs2[Hg(OTeF5)4].Hg(OTeF5)2. The calculated geometries were
      used to assess the effects of solid-state interionic interactions on the anion
      geometries. For the most part, the gross gas-phase trigonal bipyramidal (tbp)
      geometry of [Hg(OTeF5)5](3-) adheres to the predicted VSEPR geometry but
      contrasts with the solid-state anion structures, which have square-pyramidal
      geometries or geometries that lie between square pyramidal- and tbp-geometries.
      However, the bond length order calculated for the Hg-O bonds of tbp
      [Hg(OTeF5)5](3-), Hg-Oeq > Hg-Oax, is opposite to that predicted by the VSEPR
      model of molecular geometry. Natural bond orbital analyses provided the
      associated Mayer bond orders, Mayer valencies, and natural population analysis
      charges. 

PMID- 25608036
TI  - Fe-catalyzed double cross-dehydrogenative coupling of 1,3-dicarbonyl compounds
      and arylmethanes.
AB  - Fe-catalyzed tandem cross-dehydrogenative coupling of the methyl group in
      arylmethanes with 1,3-dicarbonyl compounds has been developed. The reaction
      affords one new C(sp(3))-C(sp(2)) bond and one new C(sp(3))-C(sp(3)) bond in a
      one-pot protocol. Further study suggests that this reaction might start with a
      Friedel-Crafts-type reaction (cross-dehydrogenative arylation) followed by cross
      dehydrogenative coupling with an activated methylene group under mild oxidative
      conditions. 

PMID- 25608037
TI  - Prenatal and Perinatal Factors Related to Autism, IQ, and Adaptive Functioning.
AB  - This study focused on prenatal and perinatal factors related to autism spectrum
      disorder (ASD). The authors hypothesized that mothers who exposed their infants
      to intrauterine toxicity or who had complications with labor or delivery would be
      more likely to give birth to individuals with lower IQ scores, higher scores on a
      measure of ASD, and lower scores on a measure of adaptive functioning. This
      clinical sample consisted of 33 children who presented for neuropsychological
      assessment with symptoms of ASD. Results indicated that individuals with a
      history of intrauterine toxicity had lower IQ scores than individuals who did not
      have a history of intrauterine toxicity. However, no significant effects were
      found for intrauterine toxicity and ASD or adaptive functioning. Results
      indicated that individuals with a history of complications during labor and
      delivery had lower IQ scores, higher scores on a measure of ASD, and lower scores
      on a measure of adaptive functioning. Findings may lend support to the oxidative
      stress theory of ASD. 

PMID- 25608038
TI  - Pyrolysis of Cyclopentadienone: Mechanistic Insights from a Direct Measurement of
      Product Branching Ratios.
AB  - The thermal decomposition of cyclopentadienone (C5H4?O) has been studied in a
      flash pyrolysis continuous flow microreactor. Passing dilute samples of o
      phenylene sulfite (C6H4O2SO) in He through the microreactor at elevated
      temperatures yields a relatively clean source of C5H4?O. The pyrolysis of C5H4?O
      was investigated over the temperature range 1000-2000 K. Below 1600 K, we have
      identified two decomposition channels: (1) C5H4?O (+ M) -> CO + HC=C-CH?CH2 and
      (2) C5H4?O (+ M) -> CO + HC=CH + HC=CH. There is no evidence of radical or H atom
      chain reactions. To establish the thermochemistry for the pyrolysis of
      cyclopentadienone, ab initio electronic structure calculations (AE-CCSD(T)/aug-cc
      pCVQZ//AE-CCSD(T)/cc-pVQZ and anharmonic FC-CCSD(T)/ANO1 ZPEs) were used to find
      DeltafH0(C5H4?O) to be 16 +/- 1 kcal mol(-1) and DeltafH0(CH2?CH-C=CH) to be 71
      +/- 1 kcal mol(-1). The calculations predict the reaction enthalpies
      DeltarxnH0(1) to be 28 +/- 1 kcal mol(-1) (DeltarxnH298(1) is 30 +/- 1 kcal mol(
      1)) and DeltarxnH0(2) to be 66 +/- 1 kcal mol(-1) (DeltarxnH298(2) is 69 +/- 1
      kcal mol(-1)). Following pyrolysis of C5H4?O, photoionization mass spectrometry
      was used to measure the relative concentrations of HCC-CHCH2 and HCCH. Reaction 1
      dominates at low pyrolysis temperatures (1000-1400 K). At temperatures above 1400
      K, reaction 2 becomes the dominant channel. We have used the product branching
      ratios over the temperature range 1000-1600 K to extract the ratios of
      unimolecular rate coefficients for reactions 1 and 2 . If Arrhenius expressions
      are used, the difference of activation energies for reactions 1 and 2 , E2 - E1,
      is found to be 16 +/- 1 kcal mol(-1) and the ratio of the pre-exponential
      factors, A2/A1, is 7.0 +/- 0.3. 

PMID- 25608041
TI  - Synergistic effects of nucleating agents and plasticizers on the crystallization
      behavior of poly(lactic acid).
AB  - The synergistic effect of nucleating agents and plasticizers on the thermal and
      mechanical performance of PLA nanocomposites was investigated with the objective
      of increasing the crystallinity and balancing the stiffness and toughness of PLA
      mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK
      (sulfates) were compared with each other as heterogeneous nucleating agents. Both
      the DSC isothermal and non-isothermal studies indicated that talc and LAK were
      the more effective nucleating agents among the selected fillers. Poly(D-lactic
      acid) (PDLA) acted also as a nucleating agent due to the formation of the PLA
      stereocomplex. The half crystallization time was reduced by the addition of talc
      to about 2 min from 37.5 min of pure PLA by the isothermal crystallization study.
      The dynamic mechanical thermal study (DMTA) indicated that nanofillers acted as
      both reinforcement fillers and nucleating agents in relation to the higher
      storage modulus. The plasticized PLA studied by DMTA indicated a decreasing glass
      transition temperature with the increasing of the PEG content. The addition of
      nanofiller increased the Young's modulus. PEG had the plasticization effect of
      increasing the break deformation, while sharply decreasing the stiffness and
      strength of PLA. The synergistic effect of nanofillers and plasticizer achieved
      the balance between stiffness and toughness with well-controlled crystallization.

PMID- 25608042
TI  - Identification and quantitative characterization of PSORI-CM01, a Chinese
      medicine formula for psoriasis therapy, by liquid chromatography coupled with an
      LTQ Orbitrap mass spectrometer.
AB  - PSORI-CM01 is a Chinese medicine formula prepared from medicinal herbs and used
      in China for the treatment of psoriasis. However, the chemical constituents in
      PSORI-CM01 have not been clarified yet. In order to quickly define the chemical
      profiles and control the quality of PSORI-CM01 preparations, ultra-high liquid
      chromatography coupled with electrospray ionization hybrid linear trap quadrupole
      Orbitrap mass spectrometry (UHPLC-ESI-LTQ/Orbitrap-MS) was applied for
      simultaneous identification and quantification of multiple constituents. A total
      of 108 compounds, including organic acids, phenolic acids, flavonoids, and
      terpenoids, were identified or tentatively deduced on the base of their retention
      behaviors, MS and MSn data, or by comparing with reference substances and
      literature data. In addition, an optimized UHPLC-ESI-MS method was established
      for the quantitative determination of 14 marker compounds in different dosage
      forms of PSORI-CM01 preparations. The validation of the method, including spike
      recoveries, linearity, sensitivity (LOQ), precision, and repeatability, was
      carried out and demonstrated to be satisfied the requirements of quantitative
      analysis. This is the first report on the comprehensive determination of chemical
      constituents in PSORI-CM01 preparations by UHPLC-ESI-LTQ/Orbitrap mass
      spectrometry. The results suggested that the established methods would be a
      powerful and reliable analytical tool for the characterization of multi
      constituents in complex chemical system and quality control of TCM preparations. 

PMID- 25608039
TI  - The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease
      but not amyotrophic lateral sclerosis and cerebral ischemia.
AB  - Sirtuin deacetylases regulate diverse cellular pathways and influence disease
      processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2)
      deacetylase as a potential drug target to counteract neurodegeneration. In the
      present study, we characterize SIRT2 inhibition activity of the brain-permeable
      compound AK7 and examine the efficacy of this small molecule in models of
      Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia. Our
      results demonstrate that AK7 is neuroprotective in models of Parkinson's disease;
      it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic
      neuron loss in vivo. The compound does not show beneficial effects in mouse
      models of amyotrophic lateral sclerosis and cerebral ischemia. These findings
      underscore the specificity of protective effects observed here in models of
      Parkinson's disease, and previously in Huntington's disease, and support the
      development of SIRT2 inhibitors as potential therapeutics for the two
      neurodegenerative diseases. 

PMID- 25608043
TI  - Triterpenes as potentially cytotoxic compounds.
AB  - Triterpenes are compounds of natural origin, which have numerously biological
      activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti
      viral, anti-bacterial and anti-fungal. These substances can be isolated from
      plants, animals or fungi. Nowadays, when neoplasms are main cause of death,
      triterpenes can become an alternative method for treating cancer because of their
      cytotoxic properties and chemopreventive activities. 

PMID- 25608044
TI  - Inhibition of urinary macromolecule heparin on aggregation of nano-COM and nano
      COD crystals.
AB  - PURPOSE: This research aims to study the influences of heparin (HP) on the
      aggregation of nano calcium oxalate monohydrate (COM) and nano calcium oxalate
      dihydrate (COD) with mean diameter of about 50 nm. METHOD: The influences of
      different concentrations of HP on the mean diameter and Zeta potential of nano
      COM and nano COD were investigated using a nanoparticle size Zeta potential
      analyzer. RESULTS: HP could be adsorbed on the surface of nano COM and nano COD
      crystals, leading to an increase in the absolute value of Zeta potential on the
      crystals and an increase in the electrostatic repulsion force between crystals.
      Consequently, the aggregation of the crystals is reduced and the stability of the
      system is improved. The strong adsorption ability of HP was closely related to
      the -OSO3- and -COO- groups contained in the HP molecules. X-ray photoelectron
      spectroscopy confirmed the coordination of HP with Ca2+ ions of COM and COD
      crystals. CONCLUSION: HP could inhibit the aggregation of nano COM and nano COD
      crystals and increase their stability in aqueous solution, which is conducive in
      inhibiting the formation of calcium oxalate stones.

PMID- 25608046
TI  - Correlation between knee and hindfoot alignment in patients with rheumatoid
      arthritis: The effects of subtalar joint destruction.
AB  - OBJECTIVES: Compensatory hindfoot alignment for deformities at the knee level has
      been demonstrated in patients with knee osteoarthritis. However, this phenomenon
      has not been elucidated in patients with rheumatoid arthritis (RA). The aim of
      this study is to investigate the relationship between knee deformity and hindfoot
      alignment and the effect of subtalar joint destruction in patients with RA.
      METHODS: We retrospectively investigated RA patients (110 patients, 205 limbs)
      using radiographs in the standing anteroposterior knee, standing lateral foot,
      and hindfoot alignment views. The grade of destruction at the knee and subtalar
      joints was assigned using Larsen's grading system. The correlation between the
      femorotibial and tibiocalcaneal angles and the effect of joint destruction on
      this correlation were analyzed using Pearson's correlation coefficients. RESULTS:
      There was moderate correlation between the femorotibial and tibiocalcaneal angles
      in a group of knees with a Larsen grade of >= 4 (r = 0.544, p = 0.0239). This
      correlation was stronger in a group with less damaged subtalar joints with a
      Larsen grade of <= 3 (r = 0.705, p = 0.0049). CONCLUSION: These findings
      emphasized the importance of examining foot and ankles in patients with RA who
      undergo total knee arthroplasty.

PMID- 25608047
TI  - 3D morphometric analysis of laminae and facet joints in patients with
      degenerative spondylolisthesis.
AB  - OBJECTIVE: To clarify the three-dimensional (3D) morphometric characteristics of
      the spine in patients with degenerative spondylolisthesis (DS). METHODS: 3D
      morphometric analyses of laminae and facets were performed and compared for a DS
      group, an age-matched spinal canal stenosis (LCS) group, and a control group of
      young persons without spinal disease. 3D facet sagittal angles (3D-FSAs), 3D
      facet axial angle (3D-FAAs), and 3D-FAA tropism at L3 and at L4 were measured by
      extracting the 3D inferior articular process. The 3D lamina inclination angles
      (3D-LIAs) of L3 and L4 were also measured by extracting the ventral surface of
      the laminae. RESULTS: The 3D-FSAs at L4 in the DS group were significantly higher
      than for the other groups, but the difference in 3D-FSAs at L3 was not
      statistically significant among the groups. The 3D-FAAs at L4 in the DS group
      were significantly lower than in the control group. There was no significant
      difference in other factors. CONCLUSIONS: 3D morphometric analysis clarified that
      DS is significantly correlated with horizontalization (higher 3D-FSA), but is not
      correlated with sagittalization (lower 3D-FAA) and tropism (3D-FAA tropism) of
      facet joints or horizontalization of laminae (3D-LIA). There were no morphometric
      characteristics at the cranial adjacent segment of DS.

PMID- 25608045
TI  - Stability of the human Hsp90-p50Cdc37 chaperone complex against nucleotides and
      Hsp90 inhibitors, and the influence of phosphorylation by casein kinase 2.
AB  - The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37,
      which recruits a wide selection of client protein kinases. Targeted disruption of
      the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has
      emerged as an alternative strategy to treat diseases characterized by aberrant
      Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays
      we evaluated reported Hsp90 inhibitors and nucleotides for their ability to
      inhibit formation of the human Hsp90beta-p50Cdc37 complex, reconstituted in vitro
      from full-length proteins. Hsp90 inhibitors, including the proposed PPI
      inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90
      with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2
      (CK2) did not alter the thermodynamic signature of complex formation. However,
      the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 uM),
      while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The
      differential inhibitory activity of ADP suggests that phosphorylation by CK2
      primes the complex for dissociation in response to a drop in ATP/ADP levels. The
      approach applied herein provides robust assays for a comprehensive biochemical
      evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as
      phosphorylation by a kinase or the interaction with small molecule ligands. 

PMID- 25608048
TI  - Astaxanthin ameliorates cartilage damage in experimental osteoarthritis.
AB  - PURPOSE: Astaxanthin is a red-pigment carotenoid found in certain marine animals
      and plants. Astaxanthin has been shown to inhibit matrix metalloproteinases
      (MMPs) expression in vitro. However, the effect of astaxanthin on cartilage is
      still unclear. The aim of this study was to investigate the effects of
      astaxanthin on cartilage in experimental osteoarthritis (OA). METHODS: New
      Zealand rabbits underwent anterior cruciate ligament transection to induce OA in
      right knee. Rabbits received intra-articular injection containing 0.3 ml of
      vehicle (dimethyl sulfoxide) or astaxanthin (50 MUM). Injection was started on
      the day of operation, and the injection were performed once weekly for six
      consecutive weeks. Then, rabbits were sacrificed and the right knees were
      harvested for study. RESULTS: Cartilage degradation was reduced by astaxanthin,
      as assessed by morphological and histological examination. Astaxanthin inhibited
      the gene expression of MMP-1, MMP-3, and MMP-13 in cartilage as compared with the
      vehicle group. CONCLUSIONS: The results suggest that astaxanthin may be
      considered as pharmaceutical agent in OA treatment.

PMID- 25608049
TI  - Long-term outcome of joint-preserving surgery by combination metatarsal
      osteotomies for shortening for forefoot deformity in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: We report the long-term outcome of joint-preserving surgery by
      combining metatarsal osteotomies for shortening for forefoot deformity in
      patients with rheumatoid arthritis (RA). METHODS: Forty-three patients (57 feet)
      aged 41.7-70.8 years (mean, 57.7 years) underwent a combination of first
      tarsometatarsal fusion and distal realignment (modified Lapidus procedure),
      shortening oblique osteotomies of the bases of metatarsals 2-4, and fifth ray
      osteotomy (modified Coughlin procedure). Patients were followed up for 64-108
      months (mean, 76.6 months). RESULTS: Average postoperative Foot Function Index
      scores for pain, disability, and activity were 10.3, 19.9, and 16.2,
      respectively. Average Japanese Society for Surgery of the Foot RA foot and ankle
      score improved significantly from 52.1 points preoperatively to 90.3 points
      postoperatively. Postoperatively, 41% of patients reported some forefoot
      stiffness, but showed no disability. Residual deformity and callosity were absent
      in all patients. Average hallux valgus and intermetatarsal angles decreased
      postoperatively from 48.5 degrees  to 8.6 degrees  and from 15.2 degrees  to 4.6
      degrees , respectively. Nonunion in two metatarsals, hardware breakage in three,
      and mild infection in one were identified during follow-up. CONCLUSIONS: With
      good perioperative medical management of RA, surgical repositioning of the
      metatarsophalangeal joints by proximal metatarsal shortening and consequent
      relaxing of the surrounding soft tissue shows successful long-term results.

PMID- 25608050
TI  - The polio endgame.
AB  - Paralytic poliomyelitis is a disease that became a public health issue at the
      beginning of the twentieth century and was more or less eliminated in developed
      countries by the early 1970s. The Global Polio Eradication Initiative of WHO has
      now eradicated endemic polio from all but three countries although re
      introductions occur. The progress in polio eradication is striking and has
      accelerated over the last few years. It is likely that it will be finally
      eradicated from the world soon, the looming issue will then be how to stop
      vaccinating or modify immunization programs safely so that poliomyelitis does not
      re-emerge. This review article discusses the history and pathogenesis of
      poliomyelitis. The progress made, and challenges in sustaining the eradication of
      this debilitating infectious disease are considered. 

PMID- 25608051
TI  - Stability of dietary polyphenols under the cell culture conditions: avoiding
      erroneous conclusions.
AB  - Most data of bioactivity from dietary polyphenols have been derived from in vitro
      cell culture experiments. In this context, little attention is paid to potential
      artifacts due to chemical instability of these natural antioxidants. An early
      degradation time ((C)T10) and half-degradation time ((C)T50) were defined to
      characterize the stability of 53 natural antioxidants incubated in Dulbecco's
      modified Eagle's medium (DMEM) at 37  degrees C. The degree of hydroxylation of
      flavones and flavonols significantly influenced the stability in order resorcinol
      type > catechol-type > pyrogallol-type, with the pyrogallol-type being least
      stable. In contrast, any glycosylation of polyphenols obviously enhanced their
      stability. However, the glycosylation was less important compared to the
      substitution pattern of the nucleus rings. Methoxylation of flavonoids with more
      than three hydroxyl groups typically improved their stability as did the
      hydrogenation of the C2?C3 double bond of flavonoids to corresponding flavanoids.
      There was no significant correlation between the antioxidant potential of
      polyphenols and their stability. Notably, the polyphenols were clearly more
      stable in human plasma than in DMEM, which may be caused by polyphenol-protein
      interactions. It is strongly suggested to carry out stability tests in parallel
      with cell culture experiments for dietary antioxidants with catechol or
      pyrogallol structures and pyrogallol-type glycosides in order to avoid artifacts.

PMID- 25608052
TI  - Spatial confinement of a Co3O4 catalyst in hollow metal-organic frameworks as a
      nanoreactor for improved degradation of organic pollutants.
AB  - We here first proposed a yolk-shell Co3O4@metal-organic frameworks (MOFs)
      nanoreactor via a facile method to accommodate sulfate radical-based advanced
      oxidation processes (SR-AOPs) into its interior cavity. The mesoporous and
      adsorptive MOFs shells allow the rapid diffusion of reactant molecules to the
      encapsulated Co3O4 active sites, and the confined high instantaneous
      concentration of reactants in the local void space is anticipated to facilitate
      the SR-AOPs. As a proof of concept, the nanoreactor was fully characterized and
      applied for catalytic degradation of 4-chlorophenol (4-CP) in the presence of
      peroxymonosulfate (PMS). The enhancement of SR-AOPs in the nanoreactor is
      demonstrated by the result that degradation efficiency of 4-CP reached almost
      100% within 60 min by using the yolk-shell Co3O4@MOFs catalysts as compared to
      only 59.6% under the same conditions for bare Co3O4 NPs. Furthermore, the
      applicability of this nanoreactor used in SR-AOPs was systematically investigated
      in terms of effect of reaction parameters and identification of intermediates and
      primary radical as well as mineralization of the reaction and stability of the
      composite. The findings of this study elucidated a new opportunity for improved
      environmental remediation. 

PMID- 25608053
TI  - Alkylresorcinol metabolites in urine and plasma as potential biomarkers of rye
      and wheat fiber consumption in prostate cancer patients and controls.
AB  - Alkylresorcinols (ARs) are phytochemicals mainly associated with rye/wheat bran.
      Plasma ARs and their plasma and urine metabolites are considered as biomarkers
      for whole-grain rye/wheat intake. However ARs metabolite day and night variations
      have not been studied in prostate cancer patients yet. We investigated ARs
      metabolites 3, 5-dihydroxy-benzoic acid (DHBA), and 3-(3, 5-dihydroxyphenyl)-1
      propanoic acid (DHPPA) in urine and plasma in prostate cancer patients and in
      control group. DHPPA in 12-h overnight urine correlated with the intake of rye
      bread and bread fiber across short time periods (3 days). Plasma DHPPA
      concentration was significantly greater in the prostate cancer group than in the
      control group. DHPPA and DHBA excretion was significantly higher in the overnight
      urine than in day urine in the prostate cancer group but not in the control
      group. DHPPA concentration in plasma in the prostate cancer group did not depend
      on the intake of rye bread in the previous day, suggesting an impaired metabolism
      of ARs metabolites in the prostate cancer group. The results of this study
      suggest DHPPA in 12-h overnight urine as a biomarker to estimate the intake of
      rye bread and bread fiber. 

PMID- 25608054
TI  - Spectral assemblage using light emitting diodes to obtain specified lighting
      characteristics.
AB  - Light emitting diodes (LEDs) are considered next-generation light sources.
      Because of their narrow emission spectrum, easy adjustment, and various other
      characteristics, LEDs can be used in many situations, especially those that
      require dimming or spectral assemblage. In this paper we discuss spectral
      assemblage with LEDs. We cover possible valid arrangements in a spectrum from 400
      to 700 nm by an exhaustive and genetic algorithm, calculate the highest luminous
      efficacy of a source for each correlated color temperature and color-rendering
      index, and present the corresponding energy distribution. 

PMID- 25608055
TI  - Transportable cavity-stabilized laser system for optical carrier frequency
      transmission experiments.
AB  - We report the design and performance of a transportable laser system at 1543 nm,
      together with its application as the source for a demonstration of optical
      carrier frequency transmission over 118 km of an installed dark fiber network.
      The laser system is based around an optical reference cavity featuring an elastic
      mounting that bonds the cavity to its support, enabling the cavity to be
      transported without additional clamping. The cavity exhibits passive fractional
      frequency insensitivity to vibration along the optical axis of 2.0*10(-11)  m(-1)
      s(2). With active fiber noise cancellation, the optical carrier frequency
      transmission achieves a fractional frequency instability, measured at the user
      end, of 2.6*10(-16) at 1 s, averaging down to below 3*10(-18) after 20,000 s. The
      fractional frequency accuracy of the transfer is better than 3*10(-18). This
      level of performance is sufficient for comparison of state-of-the-art optical
      frequency standards and is achieved in an urban fiber environment.

PMID- 25608056
TI  - Effect of constructional parameters on the performance of a surface plasmon
      resonance sensor based on a multimode polymer optical fiber.
AB  - We experimentally studied the influence of different constructional parameters on
      the performance of surface plasmon resonance (SPR) sensors based on a
      commercially available polymer step-index multimode fiber. For the first time, to
      the best of our knowledge, we experimentally investigated the influence of
      polishing depth on the characteristics of SPR sensors based on a straight
      multimode fiber. We also examined the impact of sensing length on the spectral
      position and strength of the SPR in side-polished straight fibers. To clarify
      literature contradictions concerning the effect of fiber bending on SPR, we
      experimentally investigated the performance of U-bent SPR sensing probes based on
      multimode fibers. We have shown that the SPR can be significantly amplified by
      bending the polymer fiber with stripped cladding. We also demonstrated that the
      side-polishing of U-bent sensing probes has little impact on their performance. 

PMID- 25608057
TI  - Fourier transform optical profilometry using fiber optic Lloyd's mirrors.
AB  - A fiber optic Lloyd's mirror assembly is used to obtain various optical
      interference patterns for the detection of 3D rigid body shapes. Two types of
      fiber optic Lloyd's systems are used in this work. The first consists of a single
      mode optical fiber and a highly reflecting flat mirror to produce bright and dark
      strips. The second is constructed by locating a single-mode optical fiber in a v
      groove, which is formed by two orthogonal flat mirrors to allow the generation of
      square-type interference patterns for the desired applications. The structured
      light patterns formed by these two fiber Lloyd's techniques are projected onto 3D
      objects. Fringe patterns are deformed due to the object's surface topography,
      which are captured by a digital CCD camera and processed with a Fourier transform
      technique to accomplish 3D surface topography of the object. It is demonstrated
      that the fiber-optic Lloyd's technique proposed in this work is more compact,
      more stable, and easier to configure than other existing surface profilometry
      systems, since it does not include any high-cost optical tools such as aligners,
      couplers, or 3D stages. The fringe patterns are observed to be more robust
      against environmental disturbances such as ambient temperature and vibrations. 

PMID- 25608058
TI  - Speckle reduction in holographic projection by random pixel separation with time
      multiplexing.
AB  - A speckle-reduction method with random locations of sparse object points is
      proposed for image quality improvement based on a time-multiplexing approach in
      holographic reconstruction. The object points of a reconstructed image are
      divided into groups of sparse object points. Pixel separation of the periodic
      location, in general, is used for the sparse object points. However, an unwanted
      periodic fringe pattern is caused, and it dominantly degrades the reconstructed
      image quality. The proposed random pixel separation enables the reconstructed
      image quality to improve more effectively. The numerical simulation and the
      optical experiment are presented to confirm the performance of the proposed
      method. 

PMID- 25608059
TI  - Composite electromagnetic scattering from an object situated above rough surface.
AB  - A highly efficient hybrid method combining physical optics (PO) with physical
      optics is adopted to analyze the electromagnetic (EM) scattering from a perfectly
      electric conducting object situated above the conducting rough surface. The PO
      method is applied to solve the scattering of an object and the underlying rough
      surface, respectively. And the Huygens equivalence principle and multipath
      scattering strategy are employed to deal with the mutual interactions between
      object and rough surface. To validate the efficiency of our present method, the
      EM scattering of the composite model by the hybrid PO-PO method for different
      polarizations is calculated and compared with those using the conventional method
      of moments as well as computational time and memory requirements. The
      distribution of induced surface currents on the object and rough surface are
      illustrated for different scattering paths. Finally, the influence of some
      parameters on the composite scattering is investigated and discussed in detail. 

PMID- 25608060
TI  - Interpretation of visible moire between repetitive periodic-like gratings in the
      image domain.
AB  - An image domain approach to the interpretation of visible moire phenomena in
      repetitive grating multiplicative superposition has been proposed. The local
      frequency method provides the instantaneous period and orientation of generated
      moire. These parameters of the moire have been sorted into real and pseudo
      patterns by the Fourier expansions analysis. With the combination of these two
      steps, the concept "equivalent period contribution threshold" has been
      introduced. It is found that different thresholds bring different integral
      domains and results for the calculation of average intensities of generated moire
      waveforms. This proves that different thresholds would introduce different
      average intensity distribution (macrostructure effects) in different moire
      patterns. With the local intensity variation (microstructure effects), the human
      eye would confuse different macrostructure effects but only consider them the
      same. The interpretation is that the macrostructure versus microstructure effects
      garble discernment of the human eye and result in different visible moire
      phenomena. This is significant for visible moire effects in various repetitive
      grating (both of cosinusoidal and binary patterns) superpositions in the image
      domain. It also presents and summarizes the coexistence of real and pseudo moires
      in repetitive, periodic-like layer superposition. 

PMID- 25608061
TI  - Optical test-benches for multiple source wavefront propagation and spatiotemporal
      point-spread function emulation.
AB  - Precise measurement of aberrations within an optical system is essential to
      mitigate combined effects of user-generated aberrations for the study of
      anisoplanatic imaging using optical test benches. The optical system point spread
      function (PSF) is first defined, and methods to minimize the effects of the
      optical system are discussed. User-derived aberrations, in the form of low-order
      Zernike ensembles, are introduced using a liquid crystal spatial light modulator
      (LC-SLM), and dynamic phase maps are used to study the spatiotemporal PSF. A
      versatile optical test bench is described, where the Shack Hartmann and curvature
      wavefront sensors are used to emulate the effects of wavefront propagation over
      time from two independent sources. 

PMID- 25608062
TI  - Dissipative vector soliton in a dispersion-managed fiber laser with normal
      dispersion.
AB  - We numerically study the vector dynamics of dissipative solitons (DSs) in a 2 MUm
      dispersion-managed fiber laser mode locked by a semiconductor saturable absorber
      mirror and operated in the normal dispersion regime. It is shown that the
      effective gain bandwidth is crucial for the DS generation. The steep spectral
      edges of DSs are the consequence of the interaction among the normal dispersion,
      fiber nonlinearity, gain and loss, and gain dispersion effect, etc. We
      numerically duplicate the experimental results and further explore the vector
      features of the generated DSs. Two DSs formed along the two orthogonal
      polarization directions which, incoherently coupled with each other, could
      propagate in the birefringent cavity with the same group velocity. 

PMID- 25608063
TI  - Precise control of the optical microfiber tapering process based on monitoring of
      intermodal interference.
AB  - This paper describes the effective rectification of the estimated diameter of an
      optical microfiber (OM) during the tapering process. A high-coherence laser is
      used to monitor the OM-tapering process. The evolution of the intermodal
      interference between the fundamental mode and the coupled modes can be clearly
      observed. We analyze the point in time at which the excited mode vanishes and use
      that to justify the correlative diameter of the fabricated OM for the first time,
      to the best of our knowledge. By comparing the measured cutoff time of the
      coupled LP(02) mode and the theoretically predicted value, we can judge whether
      the theoretical estimation of the OM diameter has been correctly obtained, and we
      can introduce a modification method with feedback by changing the initial
      parameters or the manufacturing conditions to ensure OM diameter accuracy. This
      identification and rectification method is helpful for precise fabrication of OMs
      with different waist lengths and waist diameters, and it can also be used to
      check the repeatability of OMs.

PMID- 25608064
TI  - Generation of broadband laser by high-frequency bulk phase modulator with
      multipass configuration.
AB  - A new technique is presented for obtaining a large broadband nanosecond-laser
      pulse. This technique is based on multipass phase modulation of a single
      frequency nanosecond-laser pulse from the integrated front-end source, and it is
      able to shape the temporal profile of the pulse arbitrarily, making this approach
      attractive for high-energy-density physical experiments in current laser fusion
      facilities. Two kinds of cavity configuration for multipass modulation are
      proposed, and the performances of both of them are discussed theoretically in
      detail for the first time to our knowledge. Simulation results show that the
      bandwidth of the generated laser pulse by this approach can achieve more than 100
      nm in principle if adjustment accuracy of the time interval between contiguous
      passes is controlled within 0.1% of a microwave period. In our preliminary
      experiment, a 2 ns laser pulse with 1.35-nm bandwidth in 1053 nm is produced via
      this technique, which agrees well with the theoretical result. Owing to an all
      solid-state structure, the energy of the pulse achieves 25 MUJ. In the future,
      with energy compensation and spectrum filtering, this technique is expected to
      generate a nanosecond-laser pulse of 3 nm or above bandwidth with energy of about
      100 MUJ. 

PMID- 25608065
TI  - Adaptive total variation-based spectral deconvolution with the split Bregman
      method.
AB  - Spectroscopic data often suffer from common problems of band overlap and noise.
      This paper presents a maximum a posteriori (MAP)-based algorithm for the band
      overlap problem. In the MAP framework, the likelihood probability density
      function (PDF) is constructed with Gaussian noise assumed, and the prior PDF is
      constructed with adaptive total variation (ATV) regularization. The split Bregman
      iteration algorithm is employed to optimize the ATV spectral deconvolution model
      and accelerate the speed of the spectral deconvolution. The main advantage of
      this algorithm is that it can obtain peak structure information as well as
      suppress noise simultaneity. Simulated and real spectra experiments manifest that
      this algorithm can satisfactorily recover the overlap peaks as well as suppress
      noise and are robust to the regularization parameter. 

PMID- 25608066
TI  - Error compensation in computer generated hologram-based form testing of aspheres.
AB  - Computer-generated holograms (CGHs) are used relatively often to test aspheric
      surfaces in the case of medium and high lot sizes. Until now differently modified
      measurement setups for optical form testing interferometry have been presented,
      like subaperture stitching interferometry and scanning interferometry. In
      contrast, for testing low to medium lot sizes in research and development, a
      variety of other tactile and nontactile measurement methods have been developed.
      In the case of CGH-based interferometric form testing, measurement deviations in
      the region of several tens of nanometers typically occur. Deviations arise
      especially due to a nonperfect alignment of the asphere relative to the testing
      wavefront. Therefore, the null test is user- and adjustment-dependent, which
      results in insufficient repeatability and reproducibility of the form errors.
      When adjusting a CGH, an operator usually performs a minimization of the spatial
      frequency of the fringe pattern. An adjustment to the ideal position, however,
      often cannot be performed with sufficient precision by the operator as the
      position of minimum spatial fringe density is often not unique, which also
      depends on the asphere. Thus, the scientific and technical objectives of this
      paper comprise the development of a simulation-based approach to explain and
      quantify typical experimental errors due to misalignment of the specimen toward a
      CGH in an optical form testing measurement system. A further step is the
      programming of an iterative method to realize a virtual optimized realignment of
      the system on the basis of Zernike polynomial decomposition, which should allow
      for the calculation of the measured form for an ideal alignment and thus a
      careful subtraction of a typical alignment-based form error. To validate the
      simulation-based findings, a series of systematic experiments is performed with a
      recently developed hexapod positioning system in order to allow an exact and
      reproducible positioning of the optical CGH-based setup. Additionally a CGH phase
      function using an exact geometric model is compared to the other approaches. The
      phase function is utilized to enhance the overall reliability of the sensitivity
      functions with regard to alignment errors in interferometric testing. 

PMID- 25608067
TI  - Volume Bragg grating narrowed high-power and highly efficient cladding-pumped
      Raman fiber laser.
AB  - High-power and highly efficient operation of a single-mode cladding-pumped Raman
      fiber laser with narrow lasing bandwidth is demonstrated. The spectral narrowing
      was realized by an external cavity containing a volume Bragg grating with a
      center wavelength of 1658 nm. A maximum output power of 10.4 W at 1658.3 nm with
      a spectral linewidth (FWHM) of ~0.1  nm was obtained for the launched pump power
      of 18.4 W, corresponding to a slope efficiency of 109% with respect to the
      launched pump power. Lasing characteristics of free-running operation are also
      evaluated and discussed. 

PMID- 25608068
TI  - Fast precalculated triangular mesh algorithm for 3D binary computer-generated
      holograms.
AB  - A new method for constructing computer-generated holograms using a precalculated
      triangular mesh is presented. The speed of calculation can be increased
      dramatically by exploiting both the precalculated base triangle and GPU parallel
      computing. Unlike algorithms using point-based sources, this method can
      reconstruct a more vivid 3D object instead of a "hollow image." In addition,
      there is no need to do a fast Fourier transform for each 3D element every time. A
      ferroelectric liquid crystal spatial light modulator is used to display the
      binary hologram within our experiment and the hologram of a base right triangle
      is produced by utilizing just a one-step Fourier transform in the 2D case, which
      can be expanded to the 3D case by multiplying by a suitable Fresnel phase plane.
      All 3D holograms generated in this paper are based on Fresnel propagation; thus,
      the Fresnel plane is treated as a vital element in producing the hologram. A
      GeForce GTX 770 graphics card with 2 GB memory is used to achieve parallel
      computing. 

PMID- 25608069
TI  - Wavefront reconstruction from tangential and sagittal curvature.
AB  - In a previous contribution [Appl. Opt.51, 8599 (2012)], a coauthor of this work
      presented a method for reconstructing the wavefront aberration from tangential
      refractive power data measured using dynamic skiascopy. Here we propose a new
      regularized least squares method where the wavefront is reconstructed not only
      using tangential but also sagittal curvature data. We prove that our new method
      provides improved quality reconstruction for typical and also for highly
      aberrated wavefronts, under a wide range of experimental error levels. Our method
      may be applied to any type of wavefront sensor (not only dynamic skiascopy) able
      to measure either just tangential or tangential plus sagittal curvature data.

PMID- 25608070
TI  - Detection of Golden apples' climacteric peak by laser biospeckle measurements.
AB  - In this paper, we report a study in which a laser biospeckle technique is used to
      detect the climacteric peak indicating the optimal ripeness of fruits. We monitor
      two batches of harvested Golden apples going through the ripening phase in low-
      and room-temperature environments, determine speckle parameters, and measure the
      emitted ethylene concentration using gas chromatography as reference method.
      Speckle results are then correlated to the emitted ethylene concentration by a
      principal component analysis. From a practical point of view, this approach
      allows us to validate biospeckle as a noninvasive and alternative method to
      respiration rate and ethylene production for climacteric peak detection as a
      ripening index. 

PMID- 25608071
TI  - Laser-induced plasma in aqueous media: numerical simulation and experimental
      validation of spatial and temporal profiles.
AB  - A numerical study of spatial and temporal distribution of a Gaussian-pulsed laser
      induced plasma in distilled water is conducted in order to understand the
      resulting electron density distribution within the plasma plume. The primary
      motivation behind this study is the recent impetus on laser-induced plasma in the
      field of microfabrication, where prediction of geometric feature information is
      paramount to understanding material removal and overall process performance. This
      simulation predicts the distribution of plasma energy density, absorption
      coefficient, and laser intensity within the focal region by using a 3D
      axisymmetric model. The model can be adapted to other nonaqueous condensed media
      and different laser wavelengths and pulse widths. This numerical model was
      experimentally validated by an ultrafast gated camera and an external power meter
      by measuring the plasma energy and residual intensity, respectively. The model
      and the experimental data show similar qualitative trends in plasma energy
      density as the beam power is increased. Also the residual intensity data obtained
      from the model is within 10% of the experimental data for near-threshold
      intensities and within 40% for super-threshold intensities. The outcomes of this
      model can be further used as an input for a hydrodynamic model to predict the
      behavior of the condensed medium or for a thermomechanical model to predict
      material removal characteristics of the plasma. 

PMID- 25608072
TI  - Application of the transport of intensity equation in determination of nonlinear
      refractive index.
AB  - We investigate the determination of nonlinear refractive index n(2), based on
      solving the transport of intensity equation (TIE) in conjunction with a pump
      probe technique. As the pump and probe beams propagate through a sample, the pump
      induced refractive index variations in the sample change the phase distribution
      of the probe beam. Using two recorded probe intensities in TIE, this phase change
      is derived, and so the nonlinear refractive index n(2) is obtained. The influence
      of some characteristics of the pump beam and noise on the accuracy of determining
      n(2) is also investigated. The simulation results show that the proposed method
      has a good capability for determining the nonlinear refractive index of
      materials.

PMID- 25608073
TI  - High-power Ho-doped all-fiber superfluorescent source pumped by a 1150  nm Raman
      fiber laser.
AB  - A broadband superfluorescent source based on 2 m long Ho-doped fiber and a 1150
      nm high-power Raman fiber laser is reported. The optical spectrum of the
      superfluorescent source spans the range from 1930 to 2110 nm. The maximum output
      power is 1.5 W, and the spectral full width at half-maximum is about 30 nm. Two
      peaks are generated in an optical spectrum when output power of the Ho-doped
      superfluorescent source is beyond ~200  mW. 

PMID- 25608074
TI  - Design of a compact polarization demultiplexer for silicon-based slot waveguides.
AB  - A compact polarization demultiplexer (P-DEMUX) composed of a microring resonator
      in strip waveguides and two bus channels in slot waveguides is proposed and
      characterized. The modal indices of the TM modes for slot and strip waveguides
      have comparable values, while those for the TE modes show large differences. With
      these unique properties, the input TE mode can directly output from the through
      port with nearly neglected coupling, while the input TM mode can efficiently
      output from the drop port at the resonant wavelength. Results show that a P-DEMUX
      with a radius of 3.069 MUm is achieved, where the extinction ratios are ~29.85
      and 24.23 dB, respectively, for TE and TM modes, and the insertion losses are
      ~0.45 and 0.26 dB, respectively, at the wavelength of 1550 nm. Moreover,
      fabrication tolerances to the structural parameters are investigated and field
      evolution along the propagation distance through the P-DEMUX is demonstrated. 

PMID- 25608075
TI  - Transverse Bragg reflection filtering in a dielectric waveguide.
AB  - We demonstrate that transverse Bragg stacks symmetrically placed about a
      dielectric waveguide can effectively filter a fundamental mode in the dielectric
      waveguide. A narrow bandpass dielectric waveguide filter based on transverse
      Bragg reflection is proposed and investigated numerically. The results calculated
      indicate that for the filter with Bragg stacks of longitudinal length 3.86 MUm,
      there is high transmission (>=95%) in the wavelength range of 1294-1326 nm,
      whereas there is loss as high as 93.4% at 1550 nm. Owing to its simple and
      compact structure, this filter is expected to be applied to highly dense photonic
      integrated circuits. 

PMID- 25608076
TI  - Topology optimization-based lightweight primary mirror design of a large-aperture
      space telescope.
AB  - For the large-aperture space telescope, the lightweight primary mirror design
      with a high-quality optical surface is a critical and challenging issue. This
      work presents a topology optimization-based design procedure for a lightweight
      primary mirror and a new mirror configuration of a large-aperture space telescope
      is obtained through the presented design procedure. Inspired by the topology
      optimization method considering cast constraints, an optimization model for the
      configuration design of the mirror back is proposed, through which the
      distribution and the heights of the stiffeners on the mirror back can be
      optimized simultaneously. For the purpose of minimizing the optical surface
      deviation due to self-weight and polishing pressure loadings, the objective
      function is selected as to maximize the mirror structural stiffness, which can be
      achieved by minimizing the structural compliance. The total mass of the primary
      mirror is assigned as the constraint. In the application example, results of the
      optimized design topology for two kinds of mass constraints are presented.
      Executing the design procedure for specific requirements and postprocessing the
      topology obtained of the structure, a new mirror configuration with tree-like
      stiffeners and a multiple-arch back in double directions is proposed. A
      verification model is constructed to evaluate the design results and the finite
      element method is used to calculate the displacement of the mirror surface. Then
      the RMS deviation can be obtained after fitting the deformed surface by Zernike
      polynomials. The proposed mirror is compared with two classical mirrors in the
      optical performance, and the comparison results demonstrate the superiority of
      the new mirror configuration. 

PMID- 25608077
TI  - Detecting organic materials with a CCD camera.
AB  - Absorption bands in the near-infrared are used to detect materials composed of
      organic molecules, in scenes imaged with a conventional CCD camera. A simple
      model of reflectance spectra (between 850 and 980 nm) is proposed and tested on a
      wide range of materials. An existing vision system that was designed to detect
      materials with high water content is tested on organic materials. The system
      cannot detect materials (such as cellulose and starch) that consist of chains of
      sugars. It is able to robustly detect materials such as fats and aliphatic
      plastics (in their pure form), whose molecules are essentially long chains of
      CH(2) and CH(3) groups. The ability of the system to detect plastic objects is
      limited by inorganic additives in the plastics.

PMID- 25608078
TI  - Geometric detection based on one-dimensional laser range profiles of dynamic
      conical target.
AB  - One-dimensional laser range profiles (LRPs) contain abundant information
      regarding the shape, size, and attitude of detected objects. For a dynamic
      conical target, the variation of its size and attitude could have a significant
      effect on the projections of LRP peaks. Ground coordinates, target coordinates,
      and incident field coordinates are established to compute the LRP of dynamic
      cones. In order to inverse the size, a genetic algorithm is adopted. The cone
      heights and half-cone angles of three different cones are inversed. Moreover, the
      results are used to inverse the attitude angles at any sampling time in order to
      verify accuracy of the theory. The inversion mentioned in this paper can be
      applied in any targets of arbitrary material, shape, and attitude with great
      efficiency. 

PMID- 25608079
TI  - Wavefront sensing by means of binary intensity modulation.
AB  - We propose a kind of wavefront sensing technique by means of binary intensity
      modulation. A digital micromirror device operates as a binary intensity modulator
      and a pinhole works as a binary-aberration-mode filter. Through modulating
      intensity distribution of incident light, light emitting from the pinhole is
      capable of containing information on binary aberration coefficients. With the
      amount of light acquired by a single detector, the coefficients of binary
      aberration modes for reconstructing incident wavefront can be calculated.
      Differing from the conventional wavefront sensing technique, this method turns
      the complex two-dimensional wavefront sensing into simple total-light-intensity
      detection. The simulation experiment has validated the feasibility of the
      theoretical model. 

PMID- 25608080
TI  - Combing DGS and finite element for stress analysis using inverse boundary method.
AB  - Digital gradient sensing (DGS) data combined with the finite-element method is
      proposed for stress solutions over the stress concentration area. Boundary
      conditions for a local finite element model, that is, the nodal force along the
      boundaries, are inversely determined from experimental values obtained by the DGS
      method. The DGS method measures the Cartesian stress gradient components
      directly. The sum in Cartesian stresses at all interesting points on the surface
      is obtained from the stress gradient using the linear least squares method. Thus,
      the sum stresses are used to compute the unknown boundary conditions for the
      local model. After boundary conditions are computed, the individual stress
      components are calculated by the direct finite element method. The effectiveness
      is demonstrated by applying the proposed method to a three-point bending specimen
      under the compression problem. Results show that the boundary conditions of the
      local finite element model can be determined from the DGS data and then the
      individual stresses can be obtained by the proposed method. 

PMID- 25608081
TI  - Method of hybrid multiplexing for fiber-optic Fabry-Perot sensors utilizing
      frequency-shifted interferometry.
AB  - Experimental and theoretical research on hybrid multiplexing for fiber-optic
      Fabry-Perot (F-P) sensors based on frequency-shifted interferometry is presented.
      Four F-P sensors multiplexed in a hybrid configuration were experimentally
      investigated. The location of each multiplexed sensor was retrieved by performing
      the fast Fourier transform, and the reflection spectrum of each sensor was also
      obtained in spite of the spectral overlap, which was consistent with the results
      measured by an optical spectrum analyzer. With theoretical modeling, the maximum
      sensor number of a two-channel hybrid multiplexing system reaches 26 with
      crosstalk of less than -50  dB and a maximum frequency-domain signal-to-noise
      ratio (SNR) of ~25  dB, when the source power is 2 mW and the sensor separation
      is optimal, i.e., 40 m. And the sensor number is almost twice that multiplexed by
      a serial system under the same conditions. An SNR improvement of 3.9 dB can be
      achieved by using a Hamming window in a noise-free system compared with a Hanning
      window. In addition, we applied the experimental multiplexing system to a strain
      sensing test. The cavity lengths and cavity-length shifts of the four F-P sensors
      were demodulated, which was consistent with the actual situation. It provides a
      new feasible method to multiplex F-P sensors at large scale. 

PMID- 25608082
TI  - Analysis and optimization of a dual-core dispersion compensation fiber based on a
      12-fold photonic quasicrystal structure.
AB  - In this paper, a dual-concentric-core photonic quasicrystal fiber (DCC-PQF) with
      a 12-fold symmetric structure has been designed to compensate for dispersion
      effects. To this end, a new design based on modifying the positions of the
      nearest air holes to the central core has been proposed for dispersion
      compensation, in which ultra-high negative dispersion of about -44,000 
      ps/(nm.km) at 1.55 MUm can be estimated. In addition, by optimizing structural
      parameters, high negative dispersion for the proposed DCC-PQF has been predicted,
      approximately -12,000  ps/(nm.km) at around 1.55 MUm, with an FWHM about 42 nm in
      the wavelength ranges between 1529 and 1571 nm, which entirely covers the C
      telecommunication band. Furthermore, a dispersion relation dependency on hole-to
      hole spacing, first ring air hole diameters, as well as diameter of the air holes
      in the outer core and its position, has been investigated and discussed in
      detail. 

PMID- 25608083
TI  - Sex, eyes, and vision: male/female distinctions in ophthalmic disorders.
      Introduction.

PMID- 25608084
TI  - The use of joint incentive funding to create a Department of Veterans Affairs
      Department of Defense Vascular Surgery Program.

PMID- 25608085
TI  - Crude Garlic Extract Inhibits Cell Proliferation and Induces Cell Cycle Arrest
      and Apoptosis of Cancer Cells In Vitro.
AB  - Garlic and its lipid-based extracts have played an important medicinal role in
      humans for centuries that includes antimicrobial, hypoglycemic, and lipid
      lowering properties. The present study was to investigate the effects of crude
      garlic extract (CGE) on the proliferation of human breast, prostate, hepatic, and
      colon cancer cell lines and mouse macrophageal cells, not previously studied. The
      human cancer cell lines, such as hepatic (Hep-G2), colon (Caco-2), prostate (PC
      3), and breast (MCF-7), were propagated at 37 degrees C; air/CO2 (95:5 v/v) using
      the ATCC-formulated RPMI-1640 Medium and 10% fetal bovine serum (FBS), while the
      mouse macrophage cell line (TIB-71) was propagated at 37 degrees C; air/CO2 (95:5
      v/v) using the ATCC-formulated DMEM and 10% FBS. All cells were plated at a
      density of ~5000 cells/well. After overnight incubation, the cells were treated
      with 0.125, 0.25, 0.5, or 1 MUg/mL of CGE an additional 72 h. Inhibition of cell
      proliferation of 80-90% was observed for Hep-G2, MCF-7, TIB-71, and PC-3 cells,
      but only 40-55% for the Caco-2 cells when treated with 0.25, 0.5, or 1 MUg/mL. In
      a coculture study of Caco-2 and TIB-71 cells, inhibition of cell proliferation of
      90% was observed for Caco-2 cells compared to the 40-55% when cultured
      separately. CGE also induced cell cycle arrest and had a fourfold increase in
      caspase activity (apoptosis) in PC-3 cells when treated at a dose of 0.5 or 1
      MUg/mL. This investigation of CGE clearly highlights the fact that the lipid
      bioactive compounds in CGE have the potential as promising anticancer agents.

PMID- 25608086
TI  - Utility of the FIB-4 Index for hepatocarcinogenesis in hepatitis C virus carriers
      with normal alanine aminotransferase levels.
AB  - The FIB-4 index is a simple formula using age, aspartate aminotransferase,
      alanine aminotransferase (ALT) and platelet count to evaluate liver fibrosis. We
      investigated the ability of the FIB-4 index for hepatocarcinogenesis in hepatitis
      C virus (HCV) carriers with normal ALT levels. A total of 516 patients with ALT
      levels persistently at or below 40 IU/L during an observation period of over 3
      years were included. Factors associated with the development of HCC were
      determined. Hepatocellular carcinoma (HCC) developed in 60 of 516 patients
      (11.6%). The incidence rate of HCC at 5 and 10 years was 2.6% and 17.6%,
      respectively. When patients were categorized according to the FIB-4 index as <=
      2.0 (n = 226), >2.0 and <= 4.0 (n = 169), and > 4.0 (n = 121), the cumulative
      incidence of HCC at 5 years was 0.5%, 1.3% and 8.0%, respectively, and 2.8%,
      25.6% and 37.1% at 10 years, respectively. Patients with FIB-4 index >4.0 were at
      the highest risk (P < 0.001). Factors that were significantly associated with HCC
      in the multivariate analysis were FIB-4 index >2.0 (hazard ratio (HR), 7.690),
      FIB-4 index >4.0 (HR, 8.991), alpha-fetoprotein (AFP) >5 ng/mL (HR, 2.742), AFP
      >10 ng/mL (HR, 4.915) and total bilirubin >1.2 mg/dL (HR, 2.142). A scoring
      system for hepatocarcinogenesis that combines the FIB-4 index and AFP predicted
      patient outcomes with excellent discriminative ability. The FIB-4 index is
      strongly associated with the risk of HCC in HCV carriers with normal ALT levels.

PMID- 25608088
TI  - Interaction between emotional state and learning underlies mood instability.
AB  - Intuitively, good and bad outcomes affect our emotional state, but whether the
      emotional state feeds back onto the perception of outcomes remains unknown. Here,
      we use behaviour and functional neuroimaging of human participants to investigate
      this bidirectional interaction, by comparing the evaluation of slot machines
      played before and after an emotion-impacting wheel-of-fortune draw. Results
      indicate that self-reported mood instability is associated with a positive
      feedback effect of emotional state on the perception of outcomes. We then use
      theoretical simulations to demonstrate that such positive feedback would result
      in mood destabilization. Taken together, our results suggest that the interaction
      between emotional state and learning may play a significant role in the emergence
      of mood instability. 

PMID- 25608087
TI  - Lentinula edodes-derived polysaccharide alters the spatial structure of gut
      microbiota in mice.
AB  - Lentinula edodes-derived polysaccharides possess many therapeutic
      characteristics, including anti-tumor and immuno-modulation. The gut microbes
      play a critical role in modulation of immune function. However, the impact of
      Lentinula edodes-derived polysaccharides on the gut microbes have not yet been
      explored. In this study, high-throughput pyrosequencing technique was employed to
      investigate the effects of a new heteropolysaccharide L2 from Lentinula edodes on
      microbiota diversity and composition of small intestine, cecum, colon and distal
      end of colon (feces) in mice. The results demonstrated that along mouse intestine
      the microbiota exhibit distinctly different space distribution. L2 treatment
      reduced the diversity and evenness of gut microbiota along the intestine,
      especially in the cecum and colon. In the fecal microbial communities, the
      decrease of Bacteroidetes by significantly increasing Proteobacteria were
      observed, which were characterized by the increased Helicobacteraceae and reduced
      S24-7 at family level. Some OTUs, corresponding to Bacteroides acidifaciens,
      Alistipes and Helicobacter suncus, were found to be significantly increased in L2
      treated-mice. In particular, 4 phyla Chloroflexi, Gemmatimonadetes, Nitrospirae
      and Planctomycetes are exclusively present in L2-treated mice. This is helpful
      for further demonstrating healthy action mechanism of Lentinula edodes-derived
      polysaccharide L2. 

PMID- 25608089
TI  - Transformational leaders capitalizing on opportunities.
AB  - Many organizations have recently launched new goals, which provide strategic
      opportunities for nursing professional development specialists. Nursing
      professional development specialists are key to advancing nursing practice and
      are in unique positions to influence and leverage our expertise to promote the
      provision of safe quality care. We are transformational leaders. 

PMID- 25608090
TI  - Refine test items for accurate measurement: six valuable tips.
AB  - Nursing Professional Development (NPD) specialists frequently design test items
      to assess competence, to measure learning outcomes, and to create active learning
      experiences. This article presents six valuable tips for improving test items and
      using test results to strengthen validity of measurement. NPD specialists can
      readily apply these tips and examples to measure knowledge with greater accuracy.

PMID- 25608091
TI  - New registered nurses' personal responses to professional practice: a pilot
      study.
AB  - This pilot study employed a qualitative description design to inquire into new
      registered nurses' (RNs') personal responses to being a "new nurse." Six new RNs
      participated in semistructured interviews. The findings of this pilot study can
      be used to guide educational activities for nurse leaders and others who work
      with new RNs. Several strategies are discussed, which may ease new RNs'
      transition into professional practice. 

PMID- 25608092
TI  - Nurses' perceptions of nurse residency: identifying barriers to implementation.
AB  - The purpose of this project was to describe the benefits and components of
      successful nurse residency programs, as well as gain insight into the perceptions
      of staff nurses, nurse educators, and nurse leaders regarding value, feasibility,
      and barriers to implementing nurse residency programs in acute care settings.
      This study has important implications for implementing an effective residency
      program. 

PMID- 25608093
TI  - Traditional classroom education versus computer-based learning: how nurses learn
      about pressure ulcers.
AB  - The goal of the Nurse Professional Development specialist is to utilize the most
      effective educational strategies when educating staff nurses about pressure ulcer
      prevention. More information is needed about the effect of computer-based
      learning and traditional classroom learning on pressure ulcer education for the
      staff nurse. This study compares computer-based learning and traditional
      classroom learning on immediate and long-term knowledge while evaluating the
      impact of education on pressure ulcer risk assessment, staging, and
      documentation. 

PMID- 25608094
TI  - Development and evaluation of a workshop to support evidence-based practice
      change in long-term care.
AB  - To support evidence-based practice changes in long-term care, we used a practice
      development approach with interactive workshops to engage teams from 10
      organizations in participatory change. Data from postworkshop surveys and
      subsequent semistructured interviews indicated that participants felt empowered
      to identify a priority challenge and initiate change. Notably, the workshop
      intervention enhanced collaboration between professional and unregulated staff,
      fostered the development of shared vision, and provided the impetus to tackle
      workplace barriers to change. 

PMID- 25608095
TI  - Creating and standardizing annual chemotherapy competencies throughout a
      healthcare system.
AB  - Changes in chemotherapy delivery from inpatient to outpatient settings and
      transition from intravenous to oral administration threaten the competency level
      of chemotherapy nurses. To standardize care and demonstrate competency across
      five hospital campuses and four outpatient infusion centers, one health system
      developed a hands-on competency evaluation for chemotherapy nurses based on a
      scenario approach. Results included improved confidence, competence,
      identification of variation, and standardization of equipment, process, and
      policy. 

PMID- 25608096
TI  - Outdoor adventure program builds confidence and competence to help new graduate
      RNs become "everyday" leaders at the point of care.
AB  - A nontraditional approach to leadership development promoted successful
      transition of new graduate RN residents to professional nurses. Utilizing an
      outdoor adventure program increased nurses' feelings of competence by boosting
      their confidence, facilitating an environment where leadership at the bedside
      became an ingrained part of their nursing practice. RN residents at a Midwestern
      medical center represented only 17% of the nursing population but reshaped the
      culture of the entire organization by becoming dynamic "everyday" leaders. 

PMID- 25608097
TI  - The sensei role... is it a partial cure for "nurses eating their young"?

PMID- 25608098
TI  - The financial case for nurse residency programs, part 2.

PMID- 25608099
TI  - Using simulation to effectively employ the educator/academic liaison elements of
      practice for the nursing professional development specialist.

PMID- 25608100
TI  - The role of nursing professional development in the future of nursing.

PMID- 25608101
TI  - e-learning and innovative learning options.

PMID- 25608102
TI  - An educational pathway to fast track evidence-based practice at the bedside.
AB  - Enculturation of evidence-based practice (EBP) is a continuing challenge. This
      article describes a novel pathway for staff development educators to fast track
      the teaching-learning of the EBP skills set and the immediate full cycle
      application of the EBP process at point of care. The pathway, called EBP
      Literacy, offers an asynchronous stepwise approach to learning EBP in an
      iterative process from the bedside to bench side and back to the bedside. 

PMID- 25608104
TI  - Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic
      reticulum stress-mediated apoptosis.
AB  - Malignant gliomas are a common type of primary tumor of the central nervous
      system. In spite of current intensive therapy, the prognosis of patients with
      malignant glioma remains poor, hence the development of novel therapeutic
      modalities is necessary. Cell apoptosis is a frequent target in the development
      of anti-cancer drugs. Fatsioside A, a novel baccharane-type triterpenoid
      glycoside, is extracted from the fruits of Fatsia japonica. Previous studies have
      shown that Fatsioside A induces growth inhibition, cell cycle arrest and
      apoptosis in C6 rat glioma cells and U251 human glioma cells. However, to the
      best of our knowledge, no detailed studies have reported its effect on U87MG
      glioma cells and its exact mechanisms remain unknown. In the current study, the
      growth inhibitory effect of Fatsioside A on U87MG cells was evaluated and the
      underlying molecular mechanisms were explored. Through the use of flow cytometry
      and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was
      determined that Fatsioside A markedly inhibits the growth of U87MG cells.
      Mechanistic studies demonstrated that Fatsioside A induces growth inhibition of
      U87MG cells via the induction of endoplasmic reticulum (ER) stress, which was
      supported by the upregulation of ER stress markers, including elevated levels of
      phosphorylation of PERK and eIF2alpha, the increased expression levels of CHOP
      and the accelerated cleavage of caspase-4. The downregulation of CHOP via CHOP
      specific siRNA reduced the growth-inhibitive effect of Fatsioside A on U87MG
      cells, further confirming the role of the ER stress response in mediating
      Fatsioside A-induced growth inhibition. In conclusion, Fatsioside A inhibits
      glioma cell growth via the induction of ER stress-mediated apoptosis. This may
      provide a molecular basis for the development of Fatsioside A into a drug
      candidate for the treatment of malignant glioma.

PMID- 25608105
TI  - Counterion-activated nanoactuator: reversibly switchable killing/releasing
      bacteria on polycation brushes.
AB  - A strategy to release attached bacteria from surface-grafted bactericidal
      poly((trimethylamino)ethyl methacrylate chloride) (pTMAEMA) brushes has been
      proposed. The pTMAEMA brushes were fabricated via the surface-initiated atom
      transfer radical polymerization for contact killing of bacteria, including
      Escherichia coli, Staphylococcus epidermidis and Stenotrophomonas maltophilia.
      The bacteria-conditioning surfaces, afterward, were washed with electrolyte
      solutions containing anions with different lipophilic characteristic, charge
      density, polarity and adsorbility to quaternary ammonium groups in polymers.
      Because of the special ion-pairing interactions, the interfacial properties,
      including wettability and zeta-potential, can be manipulated in a controlled
      manner. Therefore, the counterion-assisted modulation of pTMAEMA brushes
      facilitates the bacterial release and regeneration of antimicrobial polymer
      films. The physicochemical properties of polymer brushes and their interactions
      with counterions were characterized using an ellipsometer, contact angle
      goniometer, X-ray photoelectron spectroscopy and an electrokinetic analyzer. The
      repetitive killing and releasing actions of pTMAEMA through unlocking and locking
      counterions were demonstrated, showing the robust effectiveness of the pTMAEMA
      based nanoactuator in controlling the physical action by the chemical stimuli.
      The real-world implementation of the nanoactuator was demonstrated with a
      surgical scalpel by repelling killed bacteria and retaining reusability. 

PMID- 25608106
TI  - The phase diagram of electron-doped La(2-x)Ce(x)CuO(4-delta).
AB  - Superconductivity is a striking example of a quantum phenomenon in which
      electrons move coherently over macroscopic distances without scattering. The high
      temperature superconducting oxides (cuprates) are the most studied class of
      superconductors, composed of two-dimensional CuO2 planes separated by other
      layers that control the electron concentration in the planes. A key unresolved
      issue in cuprates is the relationship between superconductivity and magnetism.
      Here we report a sharp phase boundary of static three-dimensional magnetic order
      in the electron-doped superconductor La(2-x)Ce(x)CuO(4-delta), where small
      changes in doping or depth from the surface switch the material from
      superconducting to magnetic. Using low-energy spin-polarized muons, we find that
      static magnetism disappears close to where superconductivity begins and well
      below the doping level at which dramatic changes in the transport properties are
      reported. These results indicate a higher degree of symmetry between the electron
      and hole-doped cuprates than previously thought.

PMID- 25608107
TI  - ROS-triggered signaling pathways involved in the cytotoxicity and tumor promotion
      effects of pentachlorophenol and tetrachlorohydroquinone.
AB  - Free radical-triggered tissue damage is believed to play an essential role in a
      variety of human diseases. Pentachlorophenol (PCP) is applied as a pesticide
      worldwide in both industries and homes. It is used extensively as a biocide and
      wood preservative. Tetrachlorohydroquinone (TCHQ) was proved as a major toxic
      metabolite of PCP, contributing the release of free radicals during PCP
      metabolism. PCP has been proposed as a tumor promoter; however, only limited
      knowledge is available regarding the mechanisms of tumor promotion induced by PCP
      and its metabolite, TCHQ. A growing amount of literature suggests that a link
      between reactive oxygen species (ROS) and tumor promotion could exist. Herein, we
      summarize the findings regarding the ROS-triggered signaling pathways involved in
      the cytotoxicity and tumor promotion effects of PCP and TCHQ. Some of the notable
      findings demonstrated that TCHQ can induce DNA lesions and glutathione depletion
      in mammalian cells; meanwhile, oxidative stress and apoptosis/necrosis can be
      found both in vivo and in vitro. Interestingly, PCP and TCHQ were proved as mild
      tumor promoters in two-stage tumorigenesis models, in which the possible
      mechanism could be through ROS generation and changed Bcl-2 gene expression. We
      also found significant effects of antioxidants in attenuating the oxidative
      stress, cyto- and genotoxicity, and apoptosis/necrosis induced by PCP and/or
      TCHQ. In addition, mitogen-activated protein kinase (MAPK) activation is involved
      in PCP/TCHQ-triggered cytotoxicity, as evidenced by the finding that higher doses
      of TCHQ could lead to necrosis of freshly isolated splenocytes through the
      production of a large amount of ROS and sustained ERK activation. These results
      could explain partly the underlying molecular mechanisms contributing to the
      tumorigenesis induced by PCP. However, the detailed mechanisms of free radicals
      in triggering PCP/TCHQ-mediated tumor promotion and toxicity are still not
      completely resolved and need to be investigated further. 

PMID- 25608108
TI  - Sex chromosome synapsis and recombination in male guppies.
AB  - Guppy X and Y chromosomes represent an early stage in sex chromosome divergence.
      Synapsis and recombination between X and Y chromosomes attract special attention
      because recombination suppression promotes their differentiation, but previous
      studies have given contradictory results. Linkage analysis indicated that
      recombination between X and Y was extremely rare (<10%) and occurred in the
      medial part of the Y chromosome, while cytological analysis demonstrated regular
      association between the distal ends of the X and Y at diakinesis. In this study,
      we examine pairing and recombination between X and Y chromosomes using
      immunolocalization of MLH1 to mark recombination nodules, and genomic in situ
      hybridization with a male DNA probe to identify the Y-specific heterochromatic
      region. Pairing between X and Y is initiated distally. Single crossovers were
      detected in 87% of XY synaptonemal complexes, most often in the distal region and
      less frequently in a median position indicating that end-to-end associations
      between X and Y are chiasmatic. Thus, we suggest that the very low frequency of
      recombination detected by linkage analysis in a previous study resulted from a
      lack of informative markers in distal regions. 

PMID- 25608110
TI  - Production and transformation of mixed-valent nanoparticles generated by Fe(0)
      electrocoagulation.
AB  - Mixed-valent iron nanoparticles (NP) generated electrochemically by Fe(0)
      electrocoagulation (EC) show promise for on-demand industrial and drinking water
      treatment in engineered systems. This work applies multiple characterization
      techniques (in situ Raman spectroscopy, XRD, SEM, and cryo-TEM) to investigate
      the formation and persistence of magnetite and green rust (GR) NP phases produced
      via the Fe(0) EC process. Current density and background electrolyte composition
      were examined in a controlled anaerobic system to determine the initial Fe phases
      generated as well as transformation products with aging. Fe phases were
      characterized in an aerobic EC system with both simple model electrolytes and
      real groundwater to investigate the formation and aging of Fe phases produced in
      a system representing treatment of arsenic-contaminated ground waters in South
      Asia. Two central pathways for magnetite production via Fe(0) EC were identified:
      (i) as a primary product (formation within seconds when DO absent, no
      intermediates detected) and (ii) as a transformation product of GR (from minutes
      to days depending on pH, electrolyte composition, and aging conditions). This
      study provides a better understanding of the formation conditions of magnetite,
      GR, and ferric (oxyhydr)oxides in Fe EC, which is essential for process
      optimization for varying source waters. 

PMID- 25608111
TI  - Sex affects bone morphogenetic protein type II receptor signaling in pulmonary
      artery smooth muscle cells.
AB  - RATIONALE: Major pulmonary arterial hypertension (PAH) registries report a
      greater incidence of PAH in women; mutations in the bone morphogenic protein type
      II receptor (BMPR-II) occur in approximately 80% of patients with heritable PAH
      (hPAH). OBJECTIVES: We addressed the hypothesis that women may be predisposed to
      PAH due to normally reduced basal BMPR-II signaling in human pulmonary artery
      smooth muscle cells (hPASMCs). METHODS: We examined the BMPR-II signaling pathway
      in hPASMCs derived from men and women with no underlying cardiovascular disease
      (non-PAH hPASMCs). We also determined the development of pulmonary hypertension
      in male and female mice deficient in Smad1. MEASUREMENTS AND MAIN RESULTS:
      Platelet-derived growth factor, estrogen, and serotonin induced proliferation
      only in non-PAH female hPASMCs. Female non-PAH hPASMCs exhibited reduced
      messenger RNA and protein expression of BMPR-II, the signaling intermediary
      Smad1, and the downstream genes, inhibitors of DNA binding proteins, Id1 and Id3.
      Induction of phospho-Smad1/5/8 and Id protein by BMP4 was also reduced in female
      hPASMCs. BMP4 induced proliferation in female, but not male, hPASMCs. However,
      small interfering RNA silencing of Smad1 invoked proliferative responses to BMP4
      in male hPASMCs. In male hPASMCs, estrogen decreased messenger RNA and protein
      expression of Id genes. The estrogen metabolite 4-hydroxyestradiol decreased
      phospho-Smad1/5/8 and Id expression in female hPASMCs while increasing these in
      males commensurate with a decreased proliferative effect in male hPASMCs. Female
      Smad1(+/-) mice developed pulmonary hypertension (reversed by ovariectomy).
      CONCLUSIONS: We conclude that estrogen-driven suppression of BMPR-II signaling in
      non-PAH hPASMCs derived from women contributes to a pro-proliferative phenotype
      in hPASMCs that may predispose women to PAH.

PMID- 25608112
TI  - BCR-ABL inactivates cytosolic PTEN through Casein Kinase II mediated tail
      phosphorylation.
AB  - The tumor suppressive function of PTEN is exerted within 2 different cellular
      compartments. In the cytosol-membrane, it negatively regulates PI3K-AKT pathway
      through the de-phosphorylation of phosphatidylinositol (3,4,5)-triphosphate
      (PIP3), therefore blocking one of the major signaling transduction pathways in
      tumorigenesis. In the nucleus, PTEN controls genomic stability and cellular
      proliferation through phosphatase independent mechanisms. Importantly,
      impairments in PTEN cellular compartmentalization, changes in protein levels and
      post-transductional modifications affect PTEN tumor suppressive functions.
      Targeting mechanisms that inactivate PTEN promotes apoptosis induction of cancer
      cells, without affecting normal cells, with appealing therapeutic implications.
      Recently, we have shown that BCR-ABL promotes PTEN nuclear exclusion by favoring
      HAUSP mediated PTEN de-ubiquitination in Chronic Myeloid Leukemia. Here, we show
      that nuclear exclusion of PTEN is associated with PTEN inactivation in the
      cytoplasm of CML cells. In particular, BCR-ABL promotes Casein Kinase II-mediated
      PTEN tail phosphorylation with consequent inhibition of the phosphatase activity
      toward PIP3. Targeting Casein Kinase II promotes PTEN reactivation with apoptosis
      induction. We therefore propose a novel BCR-ABL/CKII/PTEN pathway as a potential
      target to achieve synthetic lethality with tyrosine kinase inhibitors. 

PMID- 25608113
TI  - Conjugated polymer and drug co-encapsulated nanoparticles for chemo- and photo
      thermal combination therapy with two-photon regulated fast drug release.
AB  - The spatial-temporal synchronization of photothermal therapy and chemotherapy is
      highly desirable for an efficient cancer treatment with synergistic effect.
      Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal
      conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser
      responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained
      nanoparticles (NPs) exhibit good monodispersity and excellent stability, which
      can efficiently convert laser energy into thermal energy for photothermal
      therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2
      naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR
      two-photon laser irradiation, which leads to fast drug release. Furthermore, the
      surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD)
      tripeptide significantly enhances the accumulation of the NPs within integrin
      alphavbeta3 overexpressed cancer cells. The half-maximal inhibitory concentration
      (IC50) of the combination therapy is 13.7 MUg mL(-1), while the IC50 for
      chemotherapy and photothermal therapy alone is 147.8 MUg mL(-1) and 36.2 MUg mL(
      1), respectively. The combination index (C.I.) is 0.48 (<1), which indicates the
      synergistic effect for chemotherapy and PTT. These findings provide an excellent
      NIR laser regulated nanoplatform for combined cancer treatment with synergistic
      effect due to the synchronous chemo- and photo-thermal therapy. 

PMID- 25608114
TI  - 30-Day Readmission Among Elderly Medicare Beneficiaries with Type 2 Diabetes.
AB  - This study retrospectively assessed rates and risk factors for all-cause hospital
      readmission among elderly Medicare beneficiaries with type 2 diabetes mellitus
      (T2DM) aged >=65 years. Associations between 30-day readmission and patients'
      demographic, insurance, index hospital, and clinical characteristics; patient
      complexities specific to the elderly; and health care utilization were examined
      using multivariable logistic regressions. Of 202,496 elderly Medicare
      beneficiaries, 52% were female, 76% were white, the mean age was 75.8 years, and
      13.2% had all-cause 30-day readmissions. Elderly patients with cognitive
      impairment (adjusted odds ratio [aOR]=1.06, 95% confidence interval [CI]=1.01
      1.12), falls and falls risk (aOR=1.15, 95% CI=1.08-1.22), polypharmacy (aOR=1.20,
      95% CI=1.14-1.27), and urinary incontinence (aOR=1.08, 95% CI=1.01-1.15) were at
      higher risk for all-cause 30-day readmission than their counterparts without
      these complexities. As elderly-specific complexities are associated with greater
      risk for readmission, intervention programs to reduce readmission risk among
      elderly patients with T2DM should be tailored to suit the needs of elderly
      patients with extensive complexities.

PMID- 25608115
TI  - An easy approach for constructing vesicles by using aromatic molecules with beta
      cyclodextrin.
AB  - Vesicles were formed in aqueous solution using beta-cyclodextrin (beta-CD)
      complexes with a series of ultra-small aromatic molecules. The vesicles are easy
      to prepare without a complicated synthesis procedure and their structure was
      identified and characterized using various techniques, including transmission
      electron microscopy, atomic force microscopy and dynamic laser light scattering.
      Using the beta-CD/l-phenylalanine system as a representative example, the
      structural factors that caused the self-assembly were revealed using proton
      nuclear magnetic resonance, Fourier transform infrared spectroscopy and X-ray
      diffraction. In addition, the vesicular architecture could be endowed with a
      diverse range of stimuli-responses, as a consequence of the selective addition of
      various guest molecules. It is anticipated that this novel assembly strategy
      could be further extended, and that it presents new opportunities for the
      development of nanocarriers and soft materials. 

PMID- 25608116
TI  - HJV and HFE Play Distinct Roles in Regulating Hepcidin.
AB  - AIMS: Hereditary hemochromatosis (HH) is an iron overload disease that is caused
      by mutations in HFE, HJV, and several other genes. However, whether HFE-HH and
      HJV-HH share a common pathway via hepcidin regulation is currently unclear.
      Recently, some HH patients have been reported to carry concurrent mutations in
      both the HFE and HJV genes. To dissect the roles and molecular mechanisms of HFE
      and/or HJV in the pathogenesis of HH, we studied Hfe(-/-), Hjv(-/-), and Hfe(-/
      )Hjv(-/-) double-knockout mouse models. RESULTS: Hfe(-/-)Hjv(-/-) mice developed
      iron overload in multiple organs at levels comparable to Hjv(-/-) mice. After an
      acute delivery of iron, the expression of hepcidin (i.e., Hamp1 mRNA) was
      increased in the livers of wild-type and Hfe(-/-) mice, but not in either Hjv(-/
      ) or Hfe(-/-)Hjv(-/-) mice. Furthermore, iron-induced phosphorylation of
      Smad1/5/8 was not detected in the livers of Hjv(-/-) or Hfe(-/-)Hjv(-/-) mice.
      INNOVATION: We generated and phenotypically characterized Hfe(-/-)Hjv(-/-) double
      knockout mice. In addition, because they faithfully phenocopy clinical HH
      patients, these mouse models are an invaluable tool for mechanistically
      dissecting how HFE and HJV regulate hepcidin expression. CONCLUSIONS: Based on
      our results, we conclude that HFE may depend on HJV for transferrin-dependent
      hepcidin regulation. The presence of residual hepcidin in the absence of HFE
      suggests either the presence of an unknown regulator (e.g., TFR2) that is
      synergistic with HJV or that HJV is sufficient to maintain basal levels of
      hepcidin.

PMID- 25608117
TI  - Impact of LDL apheresis on aortic root atheroma in children with homozygous
      familial hypercholesterolemia.
AB  - BACKGROUND: Homozygous familial hypercholesterolemia (HFH) is a rare genetic
      disease leading to early onset atherosclerosis, due to high concentrations of LDL
      C in the blood. Aortic root atheromas may be complicated by obstruction to left
      ventricle outflow or coronary stenosis. The aim of this study was to describe the
      progression of aortic root atheroma in patients requiring lipoprotein apheresis
      before 16 years of age and to examine the requirement of these patients for
      aortic surgery. METHOD: Clinical reports, lipid profiles and echocardiogram
      results were obtained retrospectively for patients with HFH from three French
      hemapheresis centers. Data are presented as group medians. RESULTS: Twenty
      patients were included, of which 53% had aortic root atheroma (as assessed by
      echocardiogram) before starting lipoprotein apheresis. These patients began
      lipoprotein apheresis later than children without aortic root atheroma (10.3
      years old [range 5.6-15.9 years] vs. 5.0 years old [range 4.5-11.6 years],
      respectively, p < 0.05). After 16.4 years (range 2.2-22.8 years) of lipoprotein
      apheresis treatment, aortic root atheroma had progressed in 64% of patients. Five
      patients needed surgery for aortic stenosis, which was associated with a coronary
      artery by-pass for two of them. There were significantly more operations among
      patients with an aortic root atheroma at the beginning of lipoprotein apheresis
      than among patients without preexisting lesions (p < 0.01). One patient died
      after aorta replacement surgery during this period. CONCLUSION: Our results
      suggest that the initiation of lipoprotein apheresis before the onset of aortic
      root atheroma should reduce the requirement for aortic surgery.

PMID- 25608118
TI  - Mowat-Wilson syndrome.

PMID- 25608119
TI  - Circadian rhythm and profile in patients with juvenile myoclonic epilepsy and
      temporal lobe epilepsy.
AB  - OBJECTIVE: This study intended to compare the circadian rhythm and circadian
      profile between patients with juvenile myoclonic epilepsy (JME) and patients with
      temporal lobe epilepsy (TLE). METHOD: We enrolled 16 patients with JME and 37
      patients with TLE from the Outpatient Clinic of UNICAMP. We applied a
      questionnaire about sleep-wake cycle and circadian profile. RESULTS: Fourteen
      (87%) out of 16 patients with JME, and 22 out of 37 (59%) patients with TLE
      reported that they would sleep after seizure (p < 0.05). Three (19%) patients
      with JME, and 17 (46%) reported to be in better state before 10:00 AM (p < 0.05).
      CONCLUSION: There is no clear distinct profile and circadian pattern in patients
      with JME in comparison to TLE patients. However, our data suggest that most JME
      patients do not feel in better shape early in the day.

PMID- 25608120
TI  - Low levels of maximal aerobic power impair the profile of mood state in
      individuals with temporal lobe epilepsy.
AB  - OBJECTIVE: To investigate the correlation between cardiorespiratory fitness and
      mood state in individuals with temporal lobe epilepsy (TLE). METHOD: Individuals
      with TLE (n = 20) and healthy control subjects (C, n = 20) were evaluated. Self
      rating questionnaires were used to assess mood (POMS) and habitual physical
      activity (BAECKE). Cardiorespiratory fitness was evaluated by a maximal
      incremental test. RESULTS: People with TLE presented lower cardiorespiratory
      fitness; higher levels of mood disorders; and lower levels of vigor when compared
      to control health subjects. A significant negative correlation was observed
      between the levels of tension-anxiety and maximal aerobic power. CONCLUSION: Low
      levels of cardiorespiratory fitness may modify the health status of individuals
      with TLE and it may be considered a risk factor for the development of mood
      disorders.

PMID- 25608121
TI  - Mowat-Wilson syndrome: neurological and molecular study in seven patients.
AB  - OBJECTIVE: To present a seven-cases serie of Mowat-Wilson syndrome (MWS). METHOD:
      All patients with positive mutation for the ZEB2 were evaluated by a geneticist
      and a neurologist, with clinical and laboratorial characterization. RESULTS: A
      peculiar facies and mental retardation were present in all patients. The Denver
      II scale showed intense delay in all aspects, especially fine motor and adaptive.
      Acquired microcephaly was observed in five patients. Only one patient did not
      present epilepsy. Epilepsy was focal and predominating in sleep, with status
      epilepticus in three patients. The initial seizure was associated with fever in
      most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging
      studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum
      (1/7). CONCLUSION: Physicians who care for patients with mental retardation and
      epilepsy should be aware of SMW.

PMID- 25608122
TI  - Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia
      type 7: comparison and correlation with other spinocerebellar ataxias.
AB  - The spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders
      characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type
      7 (SCA7) is caused by an abnormal CAG repeat expansion and includes cerebellar
      signs associated with visual loss and ophthalmoplegia. Marked anticipation and
      dynamic mutation is observed in SCA7. Moreover, phenotype variability and very
      early onset of symptoms may occur. In this article, a large series of Brazilian
      patients with different SCA subtypes was evaluated, and we compared the age of
      onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their
      symptoms before 10-year-old. Also, occasionally the parents may have the onset of
      symptoms after their children. In conclusion, our study highlights the genetic
      anticipation phenomenon that occurs in SCA7 families. Patients with very early
      onset ataxia in the context of a remarkable family history, must be considered
      and tested for SCA7. 

PMID- 25608123
TI  - Control of diabetes and fibrinogen levels as well as improvement in health care
      might delay low cognitive performance in societies aging progressively.
AB  - OBJECTIVE: To know the prevalence and factors associated to low cognitive
      performance in a representative sample of the adult population in a society aging
      progressively. METHOD: Cross-sectional population-based study carried out in a
      three-stage sampling: 81 census tracts (primary sampling unity) were randomly
      selected, followed by 1,672 households and 2,471 participants (weighted sample)
      corresponding to the second and third stages, respectively. The outcome
      prevalence was calculated according sociodemographic, behavioral and health
      related variables. Crude and adjusted prevalence ratios were estimated using
      Poisson regression. RESULTS: The prevalence of low cognitive performance was
      high, mainly among females, and indicated linear trends into categories of age,
      schooling, income, plasma fibrinogen and self-reported health status. In
      multivariate models, gender, diabetes, fibrinogen and self-reported health status
      presented positive associations, while schooling, employment and sitting time
      presented negative associations with the outcome. CONCLUSION: Interventions
      related to diabetes and fibrinogen levels control as well as improvement in
      health care might delay low cognitive performance in societies aging
      progressively as such the study population.

PMID- 25608124
TI  - Effect of speech therapy and pharmacological treatment in prosody of
      parkinsonians.
AB  - OBJECTIVE: Parkinsonian patients usually present speech impairment. The aim of
      this study was to verify the influence of levodopa and of the adapted Lee
      Silverman Vocal Treatment(r) method on prosodic parameters employed by
      parkinsonian patients. METHOD: Ten patients with idiopathic Parkinson's disease
      using levodopa underwent recording of utterances produced in four stages:
      expressing attitudes of certainty and doubt and declarative and interrogative
      modalities. The sentences were recorded under the effect of levodopa (on),
      without the effect of levodopa (off); before and after speech therapy during the
      on and off periods. RESULTS: The speech therapy and its association with drug
      treatment promoted the improvement of prosodic parameters: increase of
      fundamental frequency measures, reduction of measures of duration and greater
      intensity. CONCLUSION: The association of speech therapy to medication treatment
      is of great value in improving the communication of parkinsonian patients.

PMID- 25608125
TI  - Clinical, imagiological and etiological spectrum of posterior reversible
      encephalopathy syndrome.
AB  - OBJECTIVE: Analyze the cases of posterior reversible encephalopathy syndrome
      (PRES) admitted in a Neurology Department during an 8-year period. METHOD:
      Retrospective observational study in a central hospital in the north of Portugal.
      RESULTS: 14 patients were identified, mean age 52.3 years. Precipitating factors
      included: eclampsia, isolated arterial hypertension, spinal trauma and autonomic
      dysreflexia, Guillain-Barre syndrome, sepsis, sarcoidosis and pulmonary
      cryptococcosis and drugs. Most patients presented posterior-predominant vasogenic
      edema lesions, however 64.2% presented frontal lesions and in 42.8% cerebellum
      was involved. Four patients also had acute ischemic lesions and 1 had hemorrhagic
      lesions. During follow-up 10 patients recovered fully, 2 recovered partially, 1
      suffered a recurrence and 2 died in hospital. CONCLUSION: PRES has many
      etiological factors. The terms posterior and reversible should be revised because
      PRES frequently involves other brain regions and it is not always reversible.
      PRES patients may develop life-threatening complications and mortality is not
      negligible.

PMID- 25608126
TI  - Validity of the Brazilian version of the Neuropsychiatric Inventory Questionnaire
      (NPI-Q).
AB  - The NPI-Q (Neuropsychiatry Inventory-Questionnaire) was developed to facilitate
      the evaluation of neuropsychiatric symptoms. This study evaluated the internal
      consistency, the test-retest reliability of the Brazilian NPI-Q version and its
      convergent validity with the original NPI. METHOD: The NPI-Q and the NPI were
      administered to 64 caregivers of dementia patients. Thirteen informants were
      asked to complete a second NPI-Q form. RESULTS: The internal consistency of the
      Brazilian NPI-Q version was 0.67 for the severity scale and 0.81 for the distress
      scale. The test-retest reliability of the total NPI-Q severity and the distress
      scales were 0.97 and 0.92, respectively (p < 0.001). There were significant
      correlations between the total NPI-Q severity score and the NPI (r = 0.75) and
      between the total NPI-Q distress score and the total NPI standard distress (r =
      0.74). CONCLUSION: The Brazilian NPI-Q version showed evidence of good
      psychometric properties and can be used in general clinical practice.

PMID- 25608127
TI  - Validation survey of the impact of urinary incontinence (IIQ-7) and inventory of
      distress urogenital (UDI-6) - the short scales - in patients with multiple
      sclerosis.
AB  - Cross-cultural adaptation and validation of the Impact Questionnaire of Urinary
      Incontinence (IIQ-7) and Urogenital Distress Inventory (UDI-6) - short scale - in
      the Brazilian population with multiple sclerosis. The IIQ-7 and UDI-6 were
      translated into Portuguese, called IIQ-7-BR and UDI-6-BR. The questionnaires were
      administered in 211 individuals selected randomly. Of these, 140 had MS according
      to McDonald criteria and 71 were included in the control group. In both
      questionnaires, the Cronbach's alpha coefficient was above 0.7. The IIQ-7-BR
      showed 94.31% concordance between the evaluated studies and UDI-6-BR, 93.33%.
      Thus, the instruments of this study were presented according to the standards
      proposed by the Instrument Review Criteria, reliability, validity and
      sensitivity, maintaining the original scales characteristics. 

PMID- 25608128
TI  - Is functional dependence of Duchenne muscular dystrophy patients determinant of
      the quality of life and burden of their caregivers?
AB  - OBJECTIVE: The relationship between functional dependence and quality of life
      (QOL) in Duchenne muscular dystrophy (DMD) patients and burden and QOL in
      caregivers is not clear. This study investigated possible relationships between
      functional dependence/QOL of DMD patients and QOL/burden of caregivers. METHOD:
      This study included 35 boys (6-17 years) and respective caregivers (above 21
      years). Caregivers answered to World Health Organization Quality of Life and
      Zarit Burden Interview questionnaires. Patients were assessed with the Motor
      Function Measure and the Autoquestionnaire Qualite de vie Enfant Image. Spearman
      correlations and linear regressions were run to investigate relationships between
      the variables. RESULTS: The occurrence of lower QOL and higher burden among the
      caregivers of patients with Duchenne muscular dystrophy was evidenced. The
      functional dependence of patients was not considered a determinant factor. Higher
      caregivers' burden was related to lower caregivers' QOL and to higher patients'
      ages.

PMID- 25608129
TI  - Placebo and nocebo effects in the neurological practice.
AB  - Knowledge of placebo and nocebo effects is essential to identify their influence
      on the results in clinical practice and clinical trials, and thereby properly
      interpret their results. It is known that the gold standard of clinical trials
      research is the double-blind, placebo-controlled, randomized clinical study. The
      objective of this review is to distinguish specific from non-specific effects, so
      that the presence of positive effects in the group that received placebo (placebo
      effect) and the presence of adverse effects in the group receiving placebo
      (nocebo effect) lead to confounding in interpreting the results. Placebo and
      nocebo effects have been considered in neurological diseases such as depression,
      pain, headache, multiple sclerosis, epilepsy. As placebo and nocebo effects are
      also present in clinical practice, the purpose of this review is to draw
      attention to their influence on neurological practice, calling attention to the
      development of measures that can minimize them. 

PMID- 25608130
TI  - Scratch Collapse Test: a new clinical test for peripheral nerve compression.

PMID- 25608131
TI  - Leukodystrophy with premature ovarian failure: think on vanishing white matter
      disease (VWMD).

PMID- 25608132
TI  - Giant symptomatic capillary telangiectasia of the brain.

PMID- 25608133
TI  - Intracerebral Granulocytic Sarcoma in recurrence of Chronic Myeloid Leukemia.

PMID- 25608134
TI  - Longus colli calcific acute tendinitis: typical features with distinct imaging
      modalities.

PMID- 25608135
TI  - Neuropsychiatry problem is not the chief clinical presentation of 2014 Western
      Africa Ebola virus infection.

PMID- 25608136
TI  - Influenza A (H1N1) pandemic vaccination - an underlying risk factor for many CNS
      complications in Brazil.

PMID- 25608138
TI  - Enhanced expression of cell-specific surface antigens on endothelial
      microparticles in sepsis-induced disseminated intravascular coagulation.
AB  - Sepsis-induced disseminated intravascular coagulation (DIC) is a major cause of
      death in patients admitted to intensive care units. Endothelial injury with
      microparticle production is reported in the pathogenesis of sepsis. Endothelial
      microparticles (EMPs) present several cell-specific surface antigens with
      different bioactivities, for example, tissue factor (TF), thrombomodulin (TM),
      and endothelial protein C receptor (EPCR). We investigated associations between
      these three different surface antigen-positive EMPs and sepsis-induced DIC. This
      cross-sectional study composed of 24 patients with sepsis and 23 healthy controls
      was conducted from November 2012 to September 2013. Blood samples were collected
      from patients within 24 h of diagnosis of severe sepsis and from healthy
      controls. Numbers of TF-positive EMPs (TF EMPs), TM-positive EMPs (TM EMPs), and
      EPCR-positive EMPs (EPCR EMPs) were measured by flow cytometry immediately
      thereafter. Acute Physiology and Chronic Health Evaluation II and Sequential
      Organ Failure Assessment scores were assessed in the severe sepsis patients at
      enrollment. We assessed DIC with the International Society of Thrombosis and
      Haemostasis (ISTH) overt DIC diagnostic criteria algorithm. Numbers of antigen
      positive EMPs were increased significantly in both severe sepsis patients and
      controls and with the increase in ISTH DIC score. Numbers of TF EMPs and EPCR
      EMPs correlated significantly with Sequential Organ Failure Assessment score, and
      numbers of EPCR EMPs correlated significantly with Acute Physiology and Chronic
      Health Evaluation II score. Numbers of the three antigen-positive EMPs were
      increased significantly in severe sepsis patients versus those in healthy
      controls and with the increase of ISTH DIC score, suggesting that the specific
      bioactivity of each antigen-positive EMP may play a role in the progression of
      sepsis-induced DIC. 

PMID- 25608139
TI  - Shock in the first 24 h of intensive care unit stay: observational study of
      protocol-based fluid management.
AB  - Precision in fluid management for shock could lead to better clinical outcomes.
      We evaluated the association of protocol-based fluid management with intensive
      care unit (ICU) and hospital mortality. We performed an observational study of
      mechanically ventilated patients admitted directly from our emergency department
      to the ICU from August 2011 to December 2013, who had circulatory shock in the
      first 24 h of ICU stay (systolic blood pressure <90 mmHg at ICU admission or
      lactate >4 mmol/L). Patients with onset of shock beyond 24 h of ICU stay were
      excluded. Protocol-based fluid management required close physician-nurse
      cooperation and computerized documentation, checking for fluid response (>=10%
      arterial pulse pressure or stroke volume increase after two consecutive 250-mL
      crystalloid boluses), and fluid loading with repeated 500-mL boluses until fluid
      response became negative. Six hundred twelve mechanically ventilated patients
      with shock (mean [+/-SD] age, 63.0 years [16.5]; 252 or 41.2% females; mean Acute
      Physiology and Chronic Health Evaluation II score, 30.2 [8.8]) were studied. The
      fluid management protocol was used 455 times for 242 patients (39.5% of 612
      patients) within the first 24 h of ICU stay, with 244 (53.6% of 455) positive
      responses. Adjusted for age, sex, Acute Physiology and Chronic Health Evaluation
      II score, comorbidity, and admission year, protocol use was associated with
      reduced ICU mortality (odds ratio, 0.60; 95% confidence interval, 0.39-0.94; P =
      0.025) but not hospital mortality (odds ratio, 0.82; 95% confidence interval,
      0.54-1.23; P = 0.369). Among mechanically ventilated patients with shock within
      the first 24 h of ICU stay, about half had positive fluid responses. Adherence to
      protocol-based fluid management was associated with improved ICU survival. 

PMID- 25608140
TI  - Transforming growth factor-beta1 protects against intestinal epithelial barrier
      dysfunction caused by hypoxia-reoxygenation.
AB  - Intestinal epithelia regulate barrier integrity when challenged by inflammation,
      oxidative stress, and microbes. Transforming growth factor-beta1 (TGF-beta1) is a
      cytokine with known beneficial effects on intestinal epithelia, including barrier
      enhancement, after exposure to proinflammatory cytokines and infectious agents.
      The aim of this study was to determine whether TGF-beta1 directly protects
      intestinal epithelia during hypoxia-reoxygenation (HR). Intestinal epithelial
      monolayers (T84, Caco-2) were exposed to either hypoxia (1% O2, 1 h) or oxidative
      stress (hydrogen peroxide, 1 mM), followed by normoxic atmosphere for different
      time points in the absence and presence of varying concentrations of TGF-beta1.
      Transepithelial electrical resistance (TER) assessed barrier function, with RNA
      extracted for reverse transcription polymerase chain reaction analysis of GPx-1,
      HIF-1, heme-oxygenase-1 (HO-1), and NOX-1. In some experiments, intestinal
      epithelia were exposed to enterohemorrhagic Escherichia coli (EHEC) O157:H7
      during the reoxygenation period and TER recorded 7 h after the infectious
      challenge. Hypoxia-reoxygenation significantly decreased TER in intestinal
      epithelia compared with normoxic controls. Transforming growth factor-beta1
      pretreatment ameliorated HR-induced epithelial barrier dysfunction in T84 (at 1 -
      3 h) and Caco-2 (1 h) monolayers. Transforming growth factor-beta1 preserved
      barrier integrity for up to 16 h after challenge with hydrogen peroxide. In TGF
      beta1-treated epithelial monolayers, only HO-1 mRNA significantly increased after
      HR (P < 0.05 vs. normoxic controls). The EHEC-induced epithelial barrier
      dysfunction was significantly worsened by intestinal HR (P < 0.05 vs. normoxia
      EHEC-infected cells), but this was not protected by TGF-beta1 pretreatment.
      Transforming growth factor-beta1 preserves loss of epithelial barrier integrity
      caused by the stress of HR via a mechanism that may involve the upregulation of
      HO-1 transcription. Targeted treatment with TGF-beta could lead to novel
      therapies in enteric diseases characterized by HR injury. 

PMID- 25608141
TI  - Chemisorption, morphology, and structure of a n-type perylene diimide derivative
      at the interface with gold: influence on devices from thin films to single
      molecules.
AB  - We have investigated thin films of a perylene diimide derivative with a cyano
      functionalized core (PDI-8CN2) deposited on Au(111) single crystals from the
      monolayer to the multilayer regime. We found that PDI-8CN2 is chemisorbed on
      gold. The molecules experience a thickness-dependent reorientation, and a 2D
      growth mode with molecular stepped terraces is achieved adopting low deposition
      rates. The obtained results are discussed in terms of their impact on field
      effect devices, also clarifying why the use of substrate/contact treatments,
      decoupling PDI-8CN2 molecules from the substrate/contacts, is beneficial for such
      devices. Our results also suggest that perylene diimide derivatives with CN bay
      functionalization are very promising candidates for single-molecule electronic
      devices.

PMID- 25608142
TI  - Rhodium-catalyzed asymmetric arylation of cyclic N-sulfonyl aryl alkyl ketimines:
      efficient access to highly enantioenriched alpha-tertiary amines.
AB  - A simple catalyst system of Rh(I)/sulfur-olefin with exceptional catalytic
      performance has been developed for the highly enantioselective arylation of
      cyclic N-sulfonyl aryl alkyl ketimines with arylboroxines/arylboronic acids.
      Optically active alpha-arylalkyl-substituted benzosultams and benzosulfamidates
      which are generally difficult to obtain were easily prepared with excellent
      stereocontrol (up to 99.9% ee). The synthetic utility of the approach was
      demonstrated by the facile construction of NMDA antagonist FR115427 and
      benzoxazinone derivatives. This protocol offers new opportunities for the
      efficient synthesis of diverse chiral alpha-tertiary amines. 

PMID- 25608144
TI  - Concurrent ossification of posterior longitudinal ligament and ossification of
      ligamentum flavum in the thoracic spine demonstrated by SPECT/CT imaging.
AB  - A 44-year-old man with rectal cancer underwent bone scintigraphy to assess
      osseous lesions for lower extremity numbness and ambulatory difficulty. Whole
      body bone scan showed increased tracer accumulation in the mid thoracic spine.
      Then SPECT combined with diagnostic CT was performed to further evaluate this
      doubtful hot spot. According to the images of SPECT/CT, the radiotracer uptake at
      the site of the T7 to T8 thoracic vertebra was confirmed to be simultaneous
      ossification of posterior longitudinal ligament complicated with ossification of
      the ligamentum flavum in the thoracic spine by pathology. 

PMID- 25608143
TI  - Alkyne hydroacylation: switching regioselectivity by tandem ruthenium catalysis.
AB  - By using tandem Ru-catalysis, internal alkynes can be coupled with aldehydes for
      the synthesis of beta,gamma-unsaturated ketones. The catalyst promotes alkyne
      transformations with high regioselectivity, with examples that include the
      differentiation of a methyl vs ethyl substituent on the alkyne. Mechanistic
      studies suggest that the regioselectivity results from a selective allene
      formation that is governed by allylic strain. 

PMID- 25608145
TI  - Extraventricular neurocytoma treated with 177Lu DOTATATE PRRT induction and
      maintenance therapies.
AB  - A 64-year-old woman with a 30-year history of recurrent sellar masses presented
      with severe headache and rapidly progressive visual field loss in the left eye.
      She was diagnosed with an extraventricular neurocytoma, which was octreotide
      positive, and was referred for PRRT (peptide receptor radionuclide therapy) with
      177Lu [DOTA0,Tyr3]octreotate (DOTATATE). After 4 induction and 4 maintenance
      treatment cycles, her headaches resolved, her vision improved, and her sellar
      mass stabilized. The use of 177Lu DOTATATE PRRT in the management of
      extraventricular neurocytoma warrants further research.

PMID- 25608146
TI  - Rhabdoid papillary meningioma treated with 177Lu DOTATATE PRRT.
AB  - An 18-year-old girl presented with a 3-year history of a recurrent skull base
      mass confirmed to be a rhabdoid papillary meningioma. The tumor was octreotide
      avid and metastatic to the lungs, thoracic lymph nodes, and bones, and she was
      referred for PRRT (peptide receptor radionuclide therapy) with 177Lu DOTATATE.
      After 3 induction treatment cycles of 177Lu DOTATATE, she experienced significant
      improvements in her symptoms; however, just before the fourth treatment, she
      developed cervical spinal cord compression and passed away shortly thereafter.
      The use of 177Lu DOTATATE therapy in the management of rhabdoid papillary
      meningioma warrants further research.

PMID- 25608147
TI  - Physiologic facial muscle uptake on 18F-FDG PET/CT by chewing-like habitual
      movement in patient with Sjogren syndrome.
AB  - An 84-year-old female patient with known Sjogren syndrome underwent 18F-FDG
      PET/CT to detect recurrence of uterine cervix cancer. Sjogren syndrome is
      autoimmune disease that typically produces symptoms of dry mouth and eyes. We
      report a case of physiologic 18F-FDG uptake on facial muscles by chewing-like
      habitual movement, which was confused with salivary retention at first. The
      physiologic FDG uptake in oral cavity and facial muscles has to be reviewed
      carefully not to be confused with abnormal uptake.

PMID- 25608148
TI  - The role of 18F-flourocholine PET/CT in biochemically relapsed prostate cancer: a
      case of osteolytic prostate metastasis.
AB  - We present the case of a 60-year-old male patient with T3b-N1, Gleason score 8,
      adenocarcinoma prostate with biochemical relapse (prostate-specific antigen, 5.2
      MUg/L) 1 year after radical treatment with 50.4-Gy 3-dimensional conformal
      radiotherapy and androgen deprivation therapy. Conventional imaging including
      contrast-enhanced abdominal CT and whole-body bone scintigraphy did not reveal
      any local recurrence or distant metastases. F-flourocholine PET/CT demonstrated a
      solitary, intensely avid (SUVmax, 9.2) osteolytic metastasis in the manubrium.
      Histopathology confirmed metastatic prostate adenocarcinoma. 

PMID- 25608149
TI  - An unusual right ventricle metastasis from mandible squamous cell carcinoma
      detected on FDG PET/CT.
AB  - A patient with history of mandible squamous cell carcinoma underwent an FDG
      PET/CT scan. A focal hypermetabolic right ventricle lesion was noted and
      suggestive of metastasis. A cardiac MRI verified the right ventricle wall mass.
      Further endomyocardial biopsy confirmed the diagnosis of metastatic squamous cell
      carcinoma. 

PMID- 25608150
TI  - Analysis of the roles of glucose transporter 1 and hexokinase 2 in the metabolism
      of glucose by extrahepatic bile duct cancer cells.
AB  - PURPOSE OF THE REPORT: Extrahepatic bile duct (EHD) cancer varies in uptake of
      FDG. The aim of the present study was to determine the role of glucose
      transporter (GLUT) 1 and hexokinase (HK) 2 in the glucose metabolism of EHD
      cancer cells using immunohistochemistry and 18F-FDG PET/CT. METHODS: Twenty-six
      patients with EHD cancer who underwent baseline PET/CT and surgery were studied.
      Biopsies were immunohistochemically analyzed using antibodies against GLUT1 and
      HK2, and the expression was scored from 0 to 4 according to the percentage of
      stained cells. SUV and tumor-to-liver ratio (T/L ratio) were obtained from 18F
      FDG PET/CT data. SUV and T/L ratio and GLUT1 and HK2 expression were compared
      with histological grades and tumor locations (proximal and distal EHD) to
      correlate glucose metabolism with the expression of GLUT1 and HK2. RESULTS: SUV,
      T/L ratio, and GLUT1 and HK2 expression did not differ as a function of
      histological grade and tumor location. GLUT1 and HK2 were expressed in 20 (76.9%)
      and 22 (84.6%) of 26 tumor biopsies, respectively. The GLUT1 score, SUV, and T/L
      ratio increased, and the GLUT1 score, but not the HK2 score, correlated
      significantly with SUV (rho = 0.648) and T/L ratio (rho = 0.703). There was no
      direct correlation between the expression of GLUT1 and that of HK2 (rho = 0.2046,
      P = 0.3161). CONCLUSIONS: Although GLUT1 and HK2 regulate intracellular
      accumulation of FDG in many cancers, only GLUT1 expression was correlated with
      FDG uptake by EHD cancers.

PMID- 25608151
TI  - Hybrid imaging for pancreatic malignancy: clinical applications, merits,
      limitations, and pitfalls.
AB  - The role of PET/CT in pancreatic malignancy is evolving with new scientific
      evidence emerging continuously. PET/CT applications in imaging the pancreas and
      its organ-specific merits, limitations, and potential pitfalls are still
      evolving. This article provides an overview of the state-of-the-art applications
      of PET/CT imaging in evaluating pancreatic malignancy, comparing with
      conventional imaging modalities, such as contrast-enhanced CT and MRI. Current
      PET/MRI is also reviewed, along with brief discussion on cost-benefit analysis. 

PMID- 25608152
TI  - Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary
      carcinoid.
AB  - PURPOSE: The aims of this study were to retrospectively evaluate and compare the
      detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative
      workup of patients with pulmonary carcinoid (PC) and to assess the utility of
      various functional indices obtained with the 2 tracers in predicting the
      histological characterization of PC, that is, typical versus atypical. METHODS:
      Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga
      DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were
      included. The semiquantitative evaluation included the SUV max, the SUV of the
      tumor relative to the maximal liver uptake for 18F-FDG (SUV T/L) or the maximal
      spleen uptake for 68Ga-DOTA-peptides (SUV T/S), the ratio between SUV max of 68Ga
      DOTA-peptides PET/CT, and the SUV max of 18F-FDG PET/CT (SUV max ratio).
      Histology was used as reference standard. RESULTS: Definitive diagnosis consisted
      of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was
      positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was
      positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga
      DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F
      FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The
      SUV max ratio was the most accurate semiquantitative index in identifying TC.
      CONCLUSIONS: Overall diagnostic performance of PET/CT in detecting PC is optimal
      when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup
      analysis, the SUV max ratio seems to be the most accurate index in predicting TC.
      Both methods should be performed when PC is suspected or when the histological
      subtype is undefined.

PMID- 25608153
TI  - Radiation-induced osteosarcoma might mimic metastatic bone lesions: a case with
      bone scan and FDG PET/CT imaging.
AB  - We report on a 53-year-old woman with osteosarcoma of the skull who underwent
      radiation therapy for metastatic brain tumor. She had a history of uterine
      endometrial cancer treated with chemotherapy and surgery 9 years previously. FDG
      PET/CT for surveillance showed nodular accumulation at the right suprainguinal
      region and very avid accumulation at the left side of the occipital bone. Bone
      scan showed increased accumulation at the same portion of the occipital bone. The
      occipital tumor was surgically removed and diagnosed as radiation-induced
      osteosarcoma. 

PMID- 25608154
TI  - Asymmetric pulmonary hypermetabolism on 18F-FDG PET/CT caused by pulmonary
      embolism.
AB  - We present a case of diffuse and moderately increased 18F-FDG uptake in the
      entire left lung on 18F-FDG PET without any morphological parenchymal
      abnormalities in a patient with recent history of esophageal adenocarcinoma
      treated by minimal invasive surgery and adjuvant chemotherapy. Contrast-enhanced
      CT revealed a large embolism in the left pulmonary artery with near total
      occlusion. In the absence of parenchymal lesions, the increased 18F-FDG uptake is
      most likely an inflammatory response to a recent ischemic insult. This case
      illustrates that asymmetric lung hypermetabolism in the absence of parenchymal
      disease can be caused by a central pulmonary embolism.

PMID- 25608155
TI  - Metabolic phenotype of stage IV lung adenocarcinoma: relationship with epidermal
      growth factor receptor mutation.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) mutation status is important in
      treatment stratification of stage IV lung adenocarcinoma. We evaluated the
      relationship between the SUV max measured on PET/CT and EGFR mutations and the
      value of SUV max in predicting EGFR mutations. PATIENTS AND METHODS: Seventy-one
      stage IV lung adenocarcinoma patients with verified EGFR mutations (48 EGFR
      mutant, 23 EGFR wild-type) having pretreatment PET/CT were retrospectively
      reviewed. SUV max values of the primary tumors (n = 71), nodal (n = 246), and
      distant metastases (n = 618) were compared between EGFR-mutant and EGFR wild-type
      adenocarcinoma by Mann-Whitney U test. The receiver operating characteristics
      curve and logistic regression were performed for factors, SUV max, age, sex, and
      smoking status. The significant predictors were assessed individually and in
      combination in discriminating EGFR mutation status. Statistical significance was
      assumed at P < 0.05 RESULTS: The metastases in EGFR-mutant adenocarcinoma had
      lower SUV max than EGFR wild-type adenocarcinoma (nodal SUV max 3.4 vs 5.5,
      distant metastasis SUV max 3.4 vs 4.7, respectively; both P < 0.001). No
      statistical significant difference was observed in the primary tumors SUV max
      between the 2 groups (SUV max 7.4 vs 8.1, P = 0.311). A receiver operating
      characteristics-derived SUV max less than or equal to 7.2 in metastasis could
      separate EGFR-mutant from EGFR wild-type adenocarcinoma (area under the curve,
      0.71-0.74; P < 0.05). SUV max was a significant independent predictor, and when
      combined with age, sex, and smoking status, it is highly predictive of EGFR
      mutation status (area under the curve, 0.90). CONCLUSIONS: Low SUV max in the
      metastasis favors the presence of EGFR mutations in stage IV lung adenocarcinoma,
      and SUV max is an independent predictor of EGFR mutations.

PMID- 25608156
TI  - Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell
      carcinomas indicate HPV status?
AB  - OBJECTIVE: The aim of this study was to explore the relationship of PET/CT
      parameters with human papillomavirus (HPV) status of oropharyngeal (OP) and oral
      cavity (OC) squamous cell carcinomas (SCCs). PATIENTS AND METHODS: We
      retrospectively reviewed 39 patients with OC and OP-SCC who underwent staging 18F
      FDG PET/CT. PET/CT parameters were measured for the primary tumor and the hottest
      involved node, including SUV max, SUV mean, SUV peak, metabolic tumor volume,
      total lesion glycolysis, standardized added metabolic activity (SAM), and
      normalized SAM. Patient characteristics were compared between HPV positive (HPV+)
      and negative (HPV-) groups. Receiver operating characteristic analysis was used
      to dichotomize PET/CT parameters into high and low. Logistic regression models
      predicting HPV status were fit for each PET/CT parameter. RESULTS: The HPV+ group
      was composed of 18 patients all with OP-SCC; the HPV- group consisted of 21
      patients, 4 OP cancer patients and 17 OC cancer patients. The HPV+ group had a
      higher proportion of N2 stage (94% vs 43%; P < 0.001). Nodal PET/CT parameters
      were higher in the HPV+ group (P < 0.01); this difference was not present for the
      primary lesion. After adjusting for sex and age, the association of higher nodal
      SUV max (odds ratio [OR], 9.67), SUV mean (OR, 10.48), SUV peak (OR 9.67),
      metabolic tumor volume (OR, 14.52), total lesion glycolysis (OR, 11.84), and SAM,
      normalized SAM (OR, 16.21) with HPV+ status remained statistically significant (P
      < 0.05). CONCLUSIONS: Nodal PET/CT parameters predict HPV status. High nodal FDG
      uptake should raise suspicion for positive HPV status in the evaluation of the
      primary lesion.

PMID- 25608157
TI  - Early postoperative 18F-FDG PET/CT in high-risk stage III colorectal cancer.
AB  - PURPOSE: PET/CT may contribute to staging modification in different phases of
      colorectal cancer (CRC) management. However, it is not routinely indicated for
      stage III CRC. This study sought to determine the role of early postoperative
      PET/CT in patients with high-risk stage III CRC. PATIENTS AND METHODS: The tumor
      registry of a tertiary medical center was searched (2004-2011) for all patients
      with stage III CRC who underwent early postoperative PET/CT because of the
      presence of high-risk factors for systemic disease. Demographic and
      clinicopathological characteristics were compared between patients found/not
      found to have metastatic disease. RESULTS: The cohort included 91 patients with a
      median age of 67 years (range, 29-90 years). Pathological FDG uptake was observed
      in 38 (41%). Of these, 14 (15% of the whole cohort) were upstaged with alteration
      of their treatment protocol, 10 (11%) had local postoperative changes, and 14
      (15%) had false-positive findings. The sensitivity and specificity of PET/CT for
      detecting metastatic disease were 100% and 69%, respectively. Elevated
      postoperative carcinoembryonic antigen and CA-19.9 levels correlated with a
      positive PET/CT (P = 0.05 and P = 0.03, respectively). The median follow-up time
      was 34 months (range, 4-85 months). The estimated 5-year survival rate was
      significantly higher in patients with a negative than a positive scan (70% vs
      42%, P < 0.0006). CONCLUSIONS: Findings on early postoperative PET/CT may
      influence staging and treatment in 15% of selected patients with high-risk stage
      III CRC. Postoperative levels of carcinoembryonic antigen and CA-19.9 may serve
      as indications for PET/CT scanning in this setting. Prospective validation is
      warranted.

PMID- 25608158
TI  - Subdiaphragmatic gallstone mimicking hepatic malignancy on FDG PET/CT.
AB  - A 70-year-old man underwent an FDG PET/CT for a possible primary liver malignancy
      or metastasis found on an abdominal MRI obtained as part of a workup for
      intermittent abdominal pain. The MRI showed an enhancing lesion at the dome of
      the right lobe of the liver. The lesion was FDG avid with a discrete central
      calcification. In conjunction with the patient's history of laparoscopic
      cholecystectomy 1 year prior, the findings were consistent with inflammation
      around a migrated subdiaphragmatic gallstone. One month after the scan, a CT
      guided percutaneous biopsy of this lesion revealed chronic inflammatory cells
      with no evidence of malignancy. 

PMID- 25608159
TI  - Early prediction by 18F-FDG PET/CT for progression-free survival and overall
      survival in patients with metastatic colorectal cancer receiving third-line
      cetuximab-based therapy.
AB  - OBJECTIVE: In metastatic colorectal cancer (mCRC) with wild-type K-ras, cetuximab
      based regimen is an option for third-line therapy. The objective of this study
      was to assess if early response evaluation by 18F-FDG PET/CT can predict
      progression-free survival (PFS) and overall survival (OS) in these patients.
      PATIENTS AND METHODS: Patients with mCRC going to receive third-line cetuximab
      based therapy were enrolled. 18F-FDG PET/CT studies were arranged at baseline and
      at the ends of the first and fourth weeks of therapy. Treatment response was
      evaluated with 2 methods: method 1 based on PET response criteria in solid tumors
      1.0 and method 2 based on the assumption that an increase in peak tumor
      metabolism implies nonresponse. Progression-free survival was counted to tumor
      progression based on the Response Evaluation Criteria in Solid Tumors 1.1 or
      death. The predictive powers for PFS and OS were analyzed using the Kaplan-Meier
      method and the log-rank test. RESULTS: Twenty-seven patients were eligible with a
      median PFS of 5.8 months and a median OS of 9.1 months. Method 2 predicts PFS (P
      = 0.001) and OS (P < 0.001) at the end of the first week, whereas method 1 does
      not. Both methods predict PFS and OS at the end of the fourth week. CONCLUSIONS:
      Early response evaluation by 18F-FDG PET/CT predicts PFS and OS in patients with
      mCRC receiving third-line cetuximab-based therapy. Early therapeutic change may
      be possible for nonresponsive patients after 1 week of treatment.

PMID- 25608160
TI  - A rare case of urachal mucinous adenocarcinoma detected by 18F-FDG PET/CT.
AB  - A 48-year-old woman presented with abdominal pain, and her initial
      investigations, which included an abdominal ultrasound and a pelvic MRI
      examination, revealed a dominant soft tissue mass abutting her left iliac bone,
      extensive pelvic adenopathy, and multiple osseous metastases. The findings were
      concerning for chondrosarcoma; however, biopsy results were consistent with
      mucinous carcinoma of unknown origin. A staging 18F-FDG PET/CT revealed a mildly
      FDG-avid soft tissue mass with scattered calcifications extending to the dome of
      the urinary bladder, highly suggestive of a primary tumor. Cystoscopy with tissue
      sampling of this mass demonstrated a primary mucinous adenocarcinoma of the
      urachus.

PMID- 25608161
TI  - A rare case of primary paranasal sinus angiosarcoma with pulmonary metastasis
      detected by 18F-FDG PET/CT.
AB  - The study reports a rare case of primary paranasal sinus angiosarcoma with
      pulmonary metastases detected by 18F-FDG PET/CT. A 29-year-old woman presented
      with nasal congestion and rhinorrhea for 6 months. CT scanning showed a large
      mass in the right maxillary sinus, which had infiltrated the surrounding tissues.
      Subsequent evaluation by 18F-FDG PET/CT indicated numerous nodules in the lung,
      in addition to the paranasal sinus mass, which exhibited elevated FDG activity.
      Histologic examination after nasal endoscopic biopsy confirmed the diagnosis as
      primary paranasal sinus angiosarcoma with pulmonary metastases.

PMID- 25608162
TI  - Incidental detection of intracranial tuberculomas on (99m)Tc-TRODAT-1 SPECT/CT.
AB  - Tc-TRODAT-1 has high affinity and specificity for dopamine transporters and is
      useful for the evaluation of presynaptic dopaminergic function, especially in
      parkinsonism. There have been a few reports of extrastriatal pathological
      accumulation of Tc-TRODAT-1. We report a patient with intracranial tuberculomas
      that were incidentally detected when he underwent Tc-TRODAT-1 scintigraphy for an
      unrelated indication. 

PMID- 25608163
TI  - Autoimmune limbic encephalitis detected on FDG brain scan performed for the
      evaluation of dementia.
AB  - Most diagnostic imagers are familiar with the classic patterns of altered
      metabolism seen in Alzheimer disease, frontal temporal dementia, and dementia
      with Lewy bodies. However, awareness of other conditions that can cause cognitive
      impairment is crucial when interpreting FDG brain PET studies. This is
      particularly true of infectious and inflammatory processes, such as viral
      encephalitis, which should be diagnosed and treated on an emergent basis. In
      addition, altered metabolism can be caused by autoimmune paraneoplastic and
      encephalitic syndromes. We report a case of autoimmune limbic encephalitis
      encountered as part of evaluation for atypical onset cognitive impairment. 

PMID- 25608164
TI  - Squamous carcinoma of the lung metastases to the patella.
AB  - We report a case of a 65-year-old man with newly diagnosed squamous carcinoma of
      the lung, who presented with worsening left-knee pain. A bone scintigraphy
      displayed an increased radioactivity in the left patella. The patient underwent
      left patellectomy. Histopathological examination revealed metastasis to the
      patella from the known lung cancer. 

PMID- 25608165
TI  - Heat-damaged RBC scan: a case of intrahepatic splenosis.
AB  - Intrahepatic splenosis results from autotransplantation of splenic tissue within
      the liver, usually after splenic trauma or splenectomy. We present a case of a 43
      year-old male patient with an incidental liver lesion discovered on abdominal
      ultrasound. The diagnosis of intrahepatic splenosis was considered after CT and
      MRI before being definitively made with Tc-labeled heat-damaged RBC scintigraphy.
      The case report illustrates the imaging characteristics of this rare location of
      abdominal splenosis. 

PMID- 25608166
TI  - Quantitative graphical analysis of simultaneous dynamic PET/MRI for assessment of
      prostate cancer.
AB  - PURPOSE: Dynamic FDG imaging for prostate cancer characterization is limited by
      generally small size and low uptake in prostate tumors. Our aim in this pilot
      study was to explore feasibility of simultaneous PET/MRI to guide localization of
      prostate lesions for dynamic FDG analysis using a graphical approach. METHODS:
      Three patients with biopsy-proven prostate cancer underwent simultaneous FDG
      PET/MRI, incorporating dynamic prostate imaging. Histology and multiparametric
      MRI findings were used to localize tumors, which in turn guided identification of
      tumors on FDG images. Regions of interest were manually placed on tumor and
      benign prostate tissue. Blood activity was extracted from a region of interest
      placed on the femoral artery on PET images. FDG data were analyzed by graphical
      analysis using the influx constant Ki (Patlak analysis) when FDG binding seemed
      irreversible and distribution volume VT (reversible graphical analysis) when FDG
      binding seemed reversible given the presence of washout. RESULTS: Given inherent
      coregistration, simultaneous acquisition facilitated use of MRI data to localize
      small lesions on PET and subsequent graphical analysis in all cases. In 2 cases
      with irreversible binding, tumor had higher Ki than benign using Patlak analysis
      (0.023 vs 0.006 and 0.019 vs 0.008 mL/cm3 per minute). In 1 case appearing
      reversible, tumor had higher VT than benign using reversible graphical analysis
      (0.68 vs 0.52 mL/cm3). CONCLUSIONS: Simultaneous PET/MRI allows localization of
      small prostate tumors for dynamic PET analysis. By taking advantage of inclusion
      of the femoral arteries in the FOV, we applied advanced PET data analysis methods
      beyond conventional static measures and without blood sampling.

PMID- 25608167
TI  - 18F-FDG PET/CT, 99mTc-MIBI, and MRI in the prediction of outcome of patients with
      multiple myeloma: a comparative study.
AB  - PURPOSE: The aim of this study was to compare the relative contribution of 18F
      FDG PET/CT, 99mTc-MIBI, and MRI in predicting progression-free survival (PFS) and
      overall survival (OS) in multiple myeloma (MM) patients. PATIENTS AND METHODS:
      Thirty-three newly diagnosed MM patients had been evaluated in a previous study
      by 18F-FDG PET/CT, 99mTc-MIBI, and spine and pelvis MRI reporting focal lesions
      and diffuse bone marrow involvement. Twenty-seven patients were then subjected to
      a mean follow-up period of 58 months, whereas 6 patients were lost. RESULTS: 18F
      FDG PET/CT, 99mTc-MIBI, and MRI were positive in 26, 24, and 22 patients,
      respectively, showing diffuse bone marrow involvement in 12, 21, and 17 patients
      and a total of 185, 56, and 39 focal lesions, respectively. At follow-up, 18
      patients showed complete or partial remission, whereas 9 patients developed
      progressive disease, 7 of which died of myeloma. Univariate and subsequent
      multivariate analysis showed that F-FDG PET/CT focal uptake and Tc-MIBI focal and
      diffuse uptake predicted PFS (P = 0.0006), whereas 18F-FDG PET/CT focal uptake
      and 99mTc-MIBI focal uptake predicted OS (P = 0.0010). Although MRI diffuse
      pattern predicted PFS at univariate analysis (P = 0.0376), it was not retained in
      the model at multivariate analysis. Receiver operating characteristic curve
      analysis showed that the number of focal lesions best discriminating for PFS and
      OS prediction was 4 and 11 for 18F-FDG PET/CT and 2 in both cases for 99mTc-MIBI,
      respectively. By Kaplan-Meier analysis and log-rank testing, PFS and OS at follow
      up were significantly better in patients showing a number of focal lesions at F
      FDG PET/CT or Tc-MIBI lower than the respective cutoff (P = 0.03, P = 0.004, and
      P < 0.0001, respectively). Finally, PFS was significantly better in patients
      showing absent/faint diffuse Tc-MIBI uptake than in those having moderate/intense
      diffuse uptake (P = 0.0012). CONCLUSIONS: 18F-FDG PET/CT and 99mTc-MIBI may be
      useful in predicting PFS and OS in myeloma patients.

PMID- 25608168
TI  - Multiple ectopic calcification in subcutaneous tissues detected by bone
      scintigraphy in a patient with chronic renal failure.
AB  - A 56-year-old man presented with swelling bilateral shoulders for 2 months. Plain
      radiograph and CT demonstrated symmetric masses with plaque calcification in
      bilateral shoulders. A Tc-MDP bone scintigraphy revealed intense radiotracer
      uptake not only in the masses of bilateral shoulders but also in the masses of
      the right buttock and the left thigh. The masses in bilateral shoulders were
      resected, and the pathological examination confirmed the ectopic calcification.
      This is a rare case of multiple ectopic calcification in subcutaneous tissues in
      a patient with chronic renal failure. 

PMID- 25608169
TI  - (18)F-FDG PET/CT and MRI findings in a patient with anti-GABA(B) receptor
      encephalitis.
AB  - Autoimmune synaptic encephalitis can occur as paraneoplastic neurological
      syndromes, which are dysfunctions of the nervous system in cancer patients. One
      such rare but treatable form is associated with GABAB (gamma-aminobutyric acid-B)
      receptor antibody. We report a 55-year-old man with small cell lung cancer who
      presented with 3 weeks of progressive seizures, memory impairment, and behavioral
      disorder. His cerebrospinal fluid anti-GABAB receptor antibody titer was
      elevated. F-FDG PET/CT revealed pronounced medial temporal hypermetabolism with
      gross hypometabolism in the rest of the brain. There were no associated
      abnormalities on MRI. He showed improvement after immunotherapy and
      chemoradiotherapy. 

PMID- 25608170
TI  - Solitary subcutaneous gouty nodule mimicking metastatic melanoma on FDG PET/CT.
AB  - A 68-year-old man with a history of malignant melanoma in the right axilla
      underwent FDG PET/CT. The images demonstrated a focally increased activity in the
      subcutaneous tissue anterior to the distal left tibia, suggestive of metastasis.
      However, a gouty tophus was diagnosed pathologically after biopsy. 

PMID- 25608171
TI  - Non-Hodgkin lymphoma dominated by multiple organ extranodal disease revealed on
      FDG PET/CT.
AB  - The definition of primary extranodal lymphoma is rather controversial and often
      complicated by the variety of lymphoma types. Here we describe FDG PET/CT
      findings in 3 pediatric patients with diffuse large B-cell non-Hodgkin lymphomas
      dominated by extranodal lesions involving multiple organs. Lymphomas arising
      primarily in extranodal sites can present significant diagnostic challenges due
      to their morphological diversity and lack of uniformity in histopathological
      classification. 

PMID- 25608172
TI  - An unusual case of ectopic ACTH syndrome due to primary retroperitoneal
      carcinoid.
AB  - A 37-year-old woman with clinical and biochemical features of ectopic
      adrenocorticotropic hormone (ACTH) syndrome underwent 68Ga DOTANOC PET/CT to
      localize the source of ectopic ACTH secretion. The images showed 35 * 45-mm
      retroperitoneal mass with significantly increased tracer uptake. Plasma-free
      metanephrines and serum chromogranin levels were normal. Whole-body 131I-MIBG
      scan including the retroperitoneal mass did not show any abnormal uptake. On
      excision, histopathology of this paravertebral abdominal mass revealed carcinoid
      tumor. We suggest the use of 68Ga DOTANOC PET/CT as a first-line imaging modality
      for localization of source of ACTH secretion in ectopic ACTH syndrome.

PMID- 25608173
TI  - High liver FDG uptake on PET/CT in patient with lymphoma diagnosed with
      hereditary hemochromatosis.
AB  - Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism
      resulting in toxic accumulation of iron in vital organs. We present a 64-year-old
      white man with non-Hodgkin lymphoma treated with high-dose chemotherapy and stem
      cell transplant that was subsequently diagnosed with hereditary hemochromatosis.
      F-FDG PET/CT was performed as routine follow-up and showed a pathological finding
      of homogeneous increased liver glucose metabolism. Increased FDG avidity in the
      liver suggested the presence of damage caused by hemochromatosis. 

PMID- 25608174
TI  - Initial experience using 99mTc-MIBI SPECT/CT for the differentiation of
      oncocytoma from renal cell carcinoma.
AB  - PURPOSE: The differentiation of oncocytoma from renal cell carcinoma (RCC)
      remains a challenge with currently available cross-sectional imaging techniques.
      As a result, a large number of patients harboring a benign oncocytoma undergo
      unnecessary surgical resection. In this study, we explored the utility of 99mTc
      MIBI SPECT/CT for the differentiation of these tumors based on the hypothesis
      that the large number of mitochondria in oncocytomas would lead to increased
      99mTc-MIBI uptake. PATIENTS AND METHODS: In total, 6 patients (3 with oncocytoma
      and 3 with RCC) were imaged with 99mTc-MIBI SPECT/CT. Relative quantification was
      performed by measuring tumor-to-normal renal parenchyma background ratios.
      RESULTS: All 3 oncocytomas demonstrated radiotracer uptake near or above the
      normal renal parenchymal uptake (range of uptake ratios, 0.85-1.78). In contrast,
      the 3 RCCs were profoundly photopenic relative to renal background (range of
      uptake ratios, 0.21-0.31). CONCLUSIONS: 99mTc-MIBI SPECT/CT appears to be of
      value in scintigraphically distinguishing benign renal oncocytoma from RCC.

PMID- 25608175
TI  - FDG PET performed at thyroid remnant ablation has a higher predictive value for
      long-term survival of high-risk patients with well-differentiated thyroid cancer
      than radioiodine uptake.
AB  - PURPOSE: The predictive value of FDG PET at thyroid remnant ablation was
      evaluated in comparison to radioiodine uptake in high-risk patients with
      differentiated thyroid cancer. PATIENTS AND METHODS: One hundred forty-one
      patients who underwent radioiodine therapy (RIT) after total thyroidectomy and
      received at least 1 further RIT due to suspected metastases were retrospectively
      analyzed. Patients had not received RIT previously. FDG PET was performed before
      thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum
      thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg
      between the first and second RIT, DeltaTg). RESULTS: Biochemical response could
      be evaluated in 80 patients; survival data could be obtained for 88 patients
      (maximum, 124 months). Biochemical response was significantly better in patients
      with radioiodine-positive metastases compared with patients with radioiodine
      negative metastases (median DeltaTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding
      survival, deaths occurred later in patients with radioiodine-positive metastases
      compared with radioiodine-negative patients; however, there was no significant
      difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05).
      Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer
      biochemical response compared with patients with FDG-negative metastases (median
      DeltaTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed
      significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P <
      0.05). CONCLUSIONS: At thyroid remnant ablation, FDG PET is more predictive for
      long-term survival, whereas radioiodine uptake is more important for short-term
      response. FDG PET performed at thyroid remnant ablation might represent a useful
      tool for management of high-risk patients with differentiated thyroid cancer.

PMID- 25608176
TI  - Tips for a physician in getting the right job, Part XXI: introduction to contract
      negotiations.
AB  - Those physicians who have excellent job prospects, and preferably have more than
      one offer, may wish to try to negotiate better terms for their employment
      contract than was initially offered. However, any negotiation must be done in a
      friendly, polite, and professional manner. This article gives many tips regarding
      contract negotiations. However, the employment contract should be discussed with
      the job seeker's family and attorney before signing it. 

PMID- 25608177
TI  - Lead (Pb) contamination of self-supply groundwater systems in coastal Madagascar
      and predictions of blood lead levels in exposed children.
AB  - Thousands of households in coastal Madagascar rely on locally manufactured
      pitcher-pump systems to provide water for drinking, cooking, and household use.
      These pumps typically include components made from lead (Pb). In this study,
      concentrations of Pb in water were monitored at 18 household pitcher pumps in the
      city of Tamatave over three sampling campaigns. Concentrations of Pb frequently
      exceeded the World Health Organization's provisional guideline for drinking water
      of 10 MUg/L. Under first-draw conditions (i.e., after a pump had been inactive
      for 1 h), 67% of samples analyzed were in excess of 10 MUg/L Pb, with a median
      concentration of 13 MUg/L. However, flushing the pump systems before collecting
      water resulted in a statistically significant (p < 0.0001) decrease in Pb
      concentrations: 35% of samples collected after flushing exceeded 10 MUg/L, with a
      median concentration of 9 MUg/L. Based on measured Pb concentrations, a
      biokinetic model estimates that anywhere from 15% to 70% of children living in
      households with pitcher pumps may be at risk for elevated blood lead levels (>5
      MUg/dL). Measured Pb concentrations in water were not correlated at statistically
      significant levels with pump-system age, well depth, system manufacturer, or
      season of sample collection; only the contact time (i.e., flushed or first-draw
      condition) was observed to correlate significantly with Pb concentrations. In two
      of the 18 systems, Pb valve weights were replaced with iron, which decreased the
      observed Pb concentrations in the water by 57-89% in one pump and by 89-96% in
      the other. Both systems produced samples exclusively below 10 MUg/L after
      substitution. Therefore, relatively straightforward operational changes on the
      part of the pump-system manufacturers and pump users might reduce Pb exposure,
      thereby helping to ensure the continued sustainability of pitcher pumps in
      Madagascar. 

PMID- 25608178
TI  - Delay between recruitment and participation impacts on preinclusion attrition.
AB  - Despite being a common aspect of psychological research, the impact of delay
      between recruitment and active participation on dropout rates has received little
      research attention. This is probably due to the intuitive sense that longer
      delays will increase the dropout rate. Preinclusion attrition diminishes sample
      sizes and may threaten data representativeness. One hundred and two university
      undergraduates were recruited to participate in a short, one-off study via Short
      Message Service (SMS). Upon receipt of an SMS indicating consent to participate,
      the researchers delayed sending the study questions for one day, one week, one
      month, or two months. Delay was significantly associated with response rate with
      an 80% response rate in the one-day delay condition, 56% at one week, and 42% at
      one month. No responses were received in the two-month delay condition. This
      research confirms that the delay between recruitment and active participation
      impacts on preinclusion attrition when conducting research via SMS. 

PMID- 25608179
TI  - beta-Aminobutyric Acid-Induced Resistance Against Root-Knot Nematodes in Rice Is
      Based on Increased Basal Defense.
AB  - The nonprotein amino acid beta-aminobutyric acid (BABA) is known to protect
      plants against various pathogens. The mode of action is relatively diverse and
      specific in different plant-pathogen systems. To extend the analysis of the mode
      of action of BABA to plant-parasitic nematodes in monocot plants, we evaluated
      the effect of BABA against the root-knot nematode (RKN) Meloidogyne graminicola
      in rice. BABA treatment of rice plants inhibited nematode penetration and
      resulted in delayed nematode and giant cell development. BABA-induced resistance
      (BABA-IR) was still functional in mutants or transgenics defective in salicylic
      acid biosynthesis and response or abscisic acid (ABA) response. Pharmacological
      inhibition of jasmonic acid (JA) and ethylene (ET) biosynthesis indicated that
      BABA-IR against rice RKN likely occurs independent of JA and ET. However,
      histochemical and biochemical quantification in combination with quantitative
      real-time reverse transcription-polymerase chain reaction data suggest that BABA
      protects rice against RKN through the activation of basal defense mechanisms of
      the plant, such as reactive oxygen species accumulation, lignin formation, and
      callose deposition. 

PMID- 25608180
TI  - ARP2/3-Mediated Actin Nucleation Associated With Symbiosome Membrane Is Essential
      for the Development of Symbiosomes in Infected Cells of Medicago truncatula Root
      Nodules.
AB  - The nitrogen-fixing rhizobia in the symbiotic infected cells of root nodules are
      kept in membrane compartments derived from the host cell plasma membrane, forming
      what are known as symbiosomes. These are maintained as individual units, with
      mature symbiosomes having a specific radial position in the host cell cytoplasm.
      The mechanisms that adapt the host cell architecture to accommodate intracellular
      bacteria are not clear. The intracellular organization of any cell depends
      heavily on the actin cytoskeleton. Dynamic rearrangement of the actin
      cytoskeleton is crucial for cytoplasm organization and intracellular trafficking
      of vesicles and organelles. A key component of the actin cytoskeleton
      rearrangement is the ARP2/3 complex, which nucleates new actin filaments and
      forms branched actin networks. To clarify the role of the ARP2/3 complex in the
      development of infected cells and symbiosomes, we analyzed the pattern of actin
      microfilaments and the functional role of ARP3 in Medicago truncatula root
      nodules. In infected cells, ARP3 protein and actin were spatially associated with
      maturing symbiosomes. Partial ARP3 silencing causes defects in symbiosome
      development; in particular, ARP3 silencing disrupts the final differentiation
      steps in functional maturation into nitrogen-fixing units. 

PMID- 25608181
TI  - Identification and Characterization of the SnTox6-Snn6 Interaction in the
      Parastagonospora nodorum-Wheat Pathosystem.
AB  - Parastagonospora nodorum is a necrotrophic fungal pathogen that causes Septoria
      nodorum blotch (SNB) (formerly Stagonospora nodorum blotch) on wheat. P. nodorum
      produces necrotrophic effectors (NE) that are recognized by dominant host
      sensitivity gene products resulting in disease development. The NE-host
      interaction is critical to inducing NE-triggered susceptibility (NETS). To date,
      seven NE-host sensitivity gene interactions, following an inverse gene-for-gene
      model, have been identified in the P. nodorum-wheat pathosystem. Here, we used a
      wheat mapping population that segregated for sensitivity to two previously
      characterized interactions (SnTox1-Snn1 and SnTox3-Snn3-B1) to identify and
      characterize a new interaction involving the NE designated SnTox6 and the host
      sensitivity gene designated Snn6. SnTox6 is a small secreted protein that induces
      necrosis on wheat lines harboring Snn6. Sensitivity to SnTox6, conferred by Snn6,
      was light-dependent and was shown to underlie a major disease susceptibility
      quantitative trait locus (QTL). No other QTL were identified, even though the P.
      nodorum isolate used in this study harbored both the SnTox1 and SnTox3 genes.
      Reverse transcription-polymerase chain reaction showed that the expression of
      SnTox1 was not detectable, whereas SnTox3 was expressed and, yet, did not play a
      significant role in disease development. This work expands our knowledge of the
      wheat-P. nodorum interaction and further establishes this system as a model for
      necrotrophic specialist pathosystems. 

PMID- 25608182
TI  - Ethylene Signaling Modulates Herbivore-Induced Defense Responses in the Model
      Legume Medicago truncatula.
AB  - One or more effectors in the labial saliva (LS) of generalist Noctuid
      caterpillars activate plant signaling pathways to modulate jasmonate (JA)
      dependent defense responses; however, the exact mechanisms involved have yet to
      be elucidated. A potential candidate in this phytohormone interplay is the
      ethylene (ET) signaling pathway. We compared the biochemical and molecular
      responses of the model legume Medicago truncatula and the ET-insensitive skl
      mutant to herbivory by fourth instar Spodoptera exigua (Hubner) caterpillars with
      intact or impaired LS secretions. Cellular oxidative stress increases rapidly
      after herbivory, as evidenced by changes in oxidized-to-reduced ascorbate (ASC)
      and glutathione (GSH) ratios. The caterpillar-specific increase in GSH ratios and
      the LS-specific increase in ASC ratios are alleviated in the skl mutant,
      indicating that ET signaling is required. Ten hours postherbivory, markers of the
      JA and JA/ET pathways are differentially expressed; MtVSP is induced and MtHEL is
      repressed in a caterpillar LS- and ET-independent manner. In contrast, expression
      of the classic marker of the systemic acquired resistance pathway, MtPR1, is
      caterpillar LS-dependent and requires ET signaling. Caterpillar LS further
      suppresses the induction of JA-related trypsin inhibitor activity in an ET
      dependent manner. Findings suggest that ET is involved in the caterpillar LS
      dependent, salicylic acid/NPR1-mediated attenuation of JA-dependent induced
      responses. 

PMID- 25608184
TI  - Strong enhancement of Faraday rotation using one-dimensional conjugated photonic
      crystals containing graphene layers.
AB  - We propose a one-dimensional conjugated photonic crystal single heterojunction
      infiltrated with a single graphene layer to achieve large Faraday rotation (FR)
      angles as well as high transmission simultaneously. The effects of the external
      magnetic field values, incidence angle, number of unit cells, layer thickness of
      constituents of the conjugated photonic crystals, chemical potential of graphene,
      and ambient temperature on the Faraday rotation angle and transmission are
      investigated. Our results reveal that both the sign reversal and shifting of the
      FR peak can be obtained by changing the width of layers in the conjugated
      photonic crystal. In the case of negative FR angle, an increase of magnetic field
      enhances the FR angle and degrades the transmission. However, in the case of
      positive FR angle, when the magnetic field increases to a certain value, the FR
      angle is improved too. Further increase of the magnetic field leads to a decrease
      of FR angle. With increasing the number of unit cells, the FR angle is enhanced
      at the cost of decreasing the transmission. It is shown that normal incidence
      results in higher FR angle and transmission. It is also demonstrated that sign
      reversal and change of the FR angle is possible by manipulating the chemical
      potential of graphene and the ambient temperature. 

PMID- 25608183
TI  - Elucidation of the chemical structure and determination of the production
      conditions for a bioactive Maillard reaction product, [5-(5,6-dihydro-4H-pyridin
      3-ylidenemethyl)furan-2-yl]methanol, isolated from a glucose-lysine heated
      mixture.
AB  - We previously isolated a bioactive molecule, named F3-A, from an aqueous glucose
      (Glc) and lysine (Lys) Maillard reaction (MR) model system. Herein, F3-A was
      verified as [5-(5,6-dihydro-4H-pyridin-3-ylidenemethyl)furan-2-yl]methanol (5)
      and was subsequently synthesized for confirmation of bioactivity. Using Taguchi
      and factorial designs, we determined that the conditions which best increased the
      yield of F3-A were at pH 6 with a sugar:amino acid ratio of 2:1 and heating time
      of 12 h at 100  degrees C. The MR mixtures containing glucose produced highest
      yield, compared to fructose, lactose, and sucrose. Both the F3-A recovered from
      Glc-Lys MR mixture and the synthesized product exhibited significant (P < 0.05),
      dose dependent, nitric oxide (NO) inhibitory activity in Caco-2 cells that was
      comparable to aminoguanidine (AG) and pyrrolidine dithiocarbamate (PDTC),
      respectively. Finally, an additional inhibitory effect of F3-A was determined
      when coincubated with AG in cytokine-induced Caco-2 cells. This bioactivity
      points to a potential role in preventing intestinal inflammation. 

PMID- 25608185
TI  - Modeling and performance analysis of vertically coupled triple microring
      resonator in the Z domain.
AB  - A theoretical model of vertically coupled triple microring resonators (VCTMRRs)
      in the Z domain is presented in this work. Delay line signal processing approach
      in Z-domain modeling is used for the performance analysis of waveguide-based
      VCTMRRs. Overall transmittance of the VCTMRR is determined in the Z domain, and
      frequency response is evaluated in a MATLAB environment. Performance in terms of
      free spectral range (FSR) and crosstalk of VCTMRR with two symmetric rings is
      compared with previously published results, and found to be in close agreement.
      VCTMRR architectures with different ring length combinations have been considered
      for the analysis. Performance of a VCTMRR with three asymmetric rings is also
      reported and compared with the performance of a VCTMRR with two symmetric rings
      in the present work. The design provides transmission characteristics where
      spurious transmission (crosstalk) at the interstitial frequencies that lie
      between the extended FSR is adequately suppressed. Group delay and dispersion
      characteristics are also presented. 

PMID- 25608186
TI  - Strain gauge using Si-based optical microring resonator.
AB  - This paper presents a strain gauge using the mechanical-optical coupling method.
      The Si-based optical microring resonator was employed as the sensing element,
      which was embedded on the microcantilevers. The experimental results show that
      applying external strain triggers a clear redshift of the output resonant
      spectrum of the structure. The sensitivity of 93.72  pm/MPa was achieved, which
      also was verified using theoretical simulations. This paper provides what we
      believe is a new method to develop micro-opto-electromechanical system (MOEMS)
      sensors. 

PMID- 25608187
TI  - High-frame-rate observation of single femtosecond laser pulse propagation in
      fused silica using an echelon and optical polarigraphy technique.
AB  - We have demonstrated high-frame-rate observations of a single femtosecond laser
      pulse propagating in transparent medium using the optical polarigraphy technique
      and an echelon. The echelon produced a spatially encoded time delay for the probe
      pulse to capture directly four successive images of an intense propagating pulse
      with picosecond time interval and femtosecond time resolution. Using this method,
      we observed the propagation process of a single femtosecond laser pulse in fused
      silica. The influence of pulse-energy fluctuation on the spatial and temporal
      distribution of the single laser pulse was visualized using the single-shot
      measurements. 

PMID- 25608188
TI  - All-optical half-adder/half-subtractor using terahertz optical asymmetric
      demultiplexer.
AB  - Logic gates are the fundamental building blocks of digital systems. Using these
      logic gates, one can perform different logic and arithmetic operations. All
      optical logic and arithmetic operations are very much expected in high-speed
      communication systems. In this paper, we present a model to perform
      addition/subtraction operations on two binary digits based on a terahertz optical
      asymmetric demultiplexer (TOAD). Using four TOAD-based switches, we have designed
      a half-adder and half-subtractor circuit. The approach to designing all-optical
      arithmetic circuits not only enhances the computational speed but is also capable
      of synthesizing light as inputs to produce the desired outputs. The main
      advantages of this circuit are that synchronization between inputs is eliminated
      and simultaneous addition and subtraction operations are realized at the outputs.
      This circuit is designed theoretically and verified through numerical
      simulations. The impact of the control pulse energy, gain recovery time, and the
      input data pulse width on the extinction ratio, contrast ratio, amplitude
      modulation, Q-factor, and relative opening of the pseudo-eye diagram of the
      switching outcome is explored and assessed by means of numerical simulations. 

PMID- 25608189
TI  - Noise sources and improved performance of a mid-wave infrared uncooled silicon
      carbide optical photodetector.
AB  - An uncooled photon detector is fabricated for the mid-wave infrared (MWIR)
      wavelength of 4.21 MUm by doping an n-type 4H-SiC substrate with gallium using a
      laser doping technique. The dopant creates a p-type energy level of 0.3 eV, which
      is the energy of a photon corresponding to the MWIR wavelength 4.21 MUm. This
      energy level was confirmed by optical absorption spectroscopy. The detection
      mechanism involves photoexcitation of carriers by the photons of this wavelength
      absorbed in the semiconductor. The resulting changes in the carrier densities at
      different energy levels modify the refractive index and, therefore, the
      reflectance of the semiconductor. This change in the reflectance constitutes the
      optical response of the detector, which can be probed remotely with a laser beam
      such as a He-Ne laser and the power of the reflected probe beam can be measured
      with a conventional laser power meter. The noise mechanisms in the probe laser,
      silicon carbide MWIR detector, and laser power meter affect the performance of
      the detector in regards to aspects such as the responsivity, noise equivalent
      temperature difference (NETD), and detectivity. For the MWIR wavelengths of 4.21
      and 4.63 MUm, the experimental detectivity of the optical photodetector of this
      study was found to be 1.07*10(10)  cm.Hz(1/2)/W, while the theoretical value was
      1.11*10(10)  cm.Hz(1/2)/W. The values of NETD are 404 and 15.5 mK based on
      experimental data for an MWIR radiation source with a temperature of 25 degrees C
      and theoretical calculations, respectively.

PMID- 25608190
TI  - Aberration design of zoom lens systems using thick lens modules.
AB  - A systematic approach for the aberration design of a zoom lens system using a
      thick lens module is presented. Each component is treated as a thick lens module
      at the beginning of the design. A thick lens module refers to a thick lens
      component with a real lens structure, like lens materials, lens curvatures, lens
      thicknesses, and lens interval distances. All nine third-order aberrations of a
      thick lens component are considered during the design. The relationship of
      component aberrations in different zoom positions can be approximated from the
      aberration shift. After minimizing the aberrations of the zoom lens system, the
      nine third-order aberrations of every lens component can be determined. Then the
      thick lens structure of every lens component can be determined after optimization
      according to their first-order properties and third-order aberration targets.
      After a third optimization for minimum practical third-order aberrations of a
      zoom lens system, the aberration design using the thick lens module is complete,
      which provides a practical zoom lens system with thick lens structures. A double
      sided telecentric zoom lens system is designed using the thick lens module in
      this paper, which shows that this method is practical for zoom lens design. 

PMID- 25608191
TI  - Geometrical parameter analysis of a high-sensitivity fiber optic angular
      displacement sensor.
AB  - In this work, we present an analysis of the influence of geometrical parameters
      on the sensitivity and linear range of a fiber optic angular displacement sensor,
      through computational simulations and experiments. The geometrical parameters
      analyzed are the lens focal length, the gap between fibers, the fiber cladding
      radii, the emitting fiber critical angle (or, equivalently, the emitting fiber
      numerical aperture), and the standoff distance (distance between the lens and the
      reflective surface). Besides, we analyze the sensor sensitivity regarding any
      spurious linear displacement. The simulation and experimental results show that
      the parameters that play the most important roles are the emitting fiber core
      radius, the lens focal length, and the light coupling efficiency, whereas the
      remaining parameters have little influence on the sensor characteristics. 

PMID- 25608192
TI  - Laser printed fiber microlens for fiber-diode coupling by direct laser writing.
AB  - A printable microlens on fiber end for coupling between a laser diode to a single
      mode fiber (SMF) is demonstrated. The fiber microlens fabricated by the novel
      technique based on laser direct writing using a quasi-Bessel beam has gained high
      coupling efficiency, long working distance, and sufficient alignment tolerance. A
      coupling efficiency of 53.5% was measured for SMF coupling at a working distance
      of 16 MUm. The tolerances for a 1-dB loss increment for translational
      displacements and angular deviations between the fiber microlens and the laser
      diode were 2.5 and 1.2 MUm, and 2.0 and 5.0 degrees, respectively. The printable
      fabrication of a microlens on a fiber endface by laser direct writing allows for
      a batch process to reproduce a multiple microlens with a high consistency in a
      simple and fast fabrication cycle, with no need of individual fiber loading and
      unloading. 

PMID- 25608193
TI  - Optical layout of autostereoscopic display that simultaneously reproduces two
      views each with full-screen resolution.
AB  - Traditional 60 Hz autostereoscopic displays with static amplitude parallax
      barriers have a half of full-screen resolution in each of the two displayed views
      of a 3D scene. The known 120 Hz autostereoscopic displays with dynamic amplitude
      parallax barriers have full-screen resolution but are characterized by essential
      light intensity losses and crosstalk in each of displayed views. The recently
      proposed autostereoscopic displays with simultaneous reproducing two image
      elements in each display pixel and with a polarization parallax barrier have full
      screen resolution. However, the existing optical layout of these displays does
      not provide optimum operating conditions for the polarization parallax barrier
      creating a tendency to degrade the contrast and color characteristics. This paper
      presents a new optical layout characterized by the rearrangement of optical
      components of the previous layout. In this approach, the highlighted problems are
      addressed without any trade-offs. Through informal subjective visual tests, this
      proposal is found to provide good contrast and good color balance in the output
      image. 

PMID- 25608194
TI  - Impact of thickness of liquid crystal layer on response rate and exponential gain
      coefficient with assistance of ZnSe film.
AB  - A response time as short as 5.4 ms and an exponential gain coefficient as large
      as 1795.0  cm(-1) were obtained in C(60) doped 4,4'-n-pentylcyanobiphenyl liquid
      crystal cells sandwiched with two indium tin oxide glass plates coated with
      nanoscale photoconductive ZnSe films, which is believed to be facilitating charge
      carrier generation and transportation and, hence, to be responsible for the fast
      response rate. The surface-mediated photorefractive effect and the ZnSe
      interlayers were both behind the high gain coefficients. The two-dimensional
      diffraction patterns observed in our system are also discussed.

PMID- 25608195
TI  - Detection techniques in low-coherence interferometry and their impact on overall
      measurement accuracy.
AB  - This paper deals with interference fringe center detection techniques used in low
      coherence interferometry for contactless 3D inspection of macroscopic objects. It
      presents a complex analysis of several frequently used detection techniques and
      shows their impact on the measurement accuracy. The analysis compares those
      techniques in terms of computational complexity, measurement accuracy, and
      resistance to optical dispersion caused by wedge-shaped optical components. 

PMID- 25608196
TI  - Equitable mirrors.
AB  - Mirror surfaces used in catadioptric sensors are often designed so as to minimize
      one particular kind of image distortion. In this article we explore some finer
      properties of equi-areal mirrors, those that feature no area distortion, and we
      propose novel ways to measure compound forms of distortion. Specifically, we
      develop new mirror surfaces with large fields of view that simultaneously
      minimize angular and areal distortion with respect to different cost functions. 

PMID- 25608197
TI  - Wide-converter lens design for a pico projector.
AB  - In this paper, we propose a concept for the design of a 0.702* wide-converter
      lens for a 0.3 in. digital micromirror device. This 0.702* wide-converter lens is
      capable of enlarging the size of the original projected image at the same
      projection distance. This 0.702* wide-converter lens is attached in front of the
      projection lens of a pico projector (PP). Compared with the projection lens of a
      PP without the 0.702* wide-converter lens, there is an increase in the size of
      the original projected image of 42.4% at the same projection distance. In other
      words, there is a saving of projection distance of 29.78% to obtain a projected
      image of the same size. 

PMID- 25608198
TI  - Improvement in angular color uniformity of white light-emitting diodes using
      screen-printed multilayer phosphor-in-glass.
AB  - Angular color uniformity (ACU) is a key optical property of white light-emitting
      diodes (WLEDs) and high ACU is strongly demanded in illumination applications. In
      this paper, a multilayer phosphor-in-glass (PiG), which can be produced by the
      screen-printing method, is proposed to improve the ACU of LED packages. The
      screen-printing method provides a feasible scheme to produce multilayer, various
      shaped PiG with a controllable pattern. Angular correlated color temperature
      (CCT) distributions of the LED packages with multilayer PiG are simulated
      numerically and measured experimentally. Optical performance of the LED package
      with optimized three-layer cone-shaped PiG is compared with that of packages with
      two-layer and one-layer PiG. The experimental measurements indicate that the
      deviation of angular CCT can be reduced from 761 to 171 K by cone-shaped PiG at
      average CCT of 6000 K. The results demonstrate that higher angular color
      uniformity can be achieved by LED packages with multilayer cone-shaped PiG. 

PMID- 25608199
TI  - Spectral shaping of an all-fiber torsional acousto-optic tunable filter.
AB  - Spectral shaping of an all-fiber torsional acousto-optic (AO) tunable filter is
      studied. The technique is based on the axial modulation of AO coupling strength
      along a highly birefringent optical fiber, which is achieved by tailoring the
      outer diameter of the fiber along its propagation axis. Two kinds of filter
      spectral shaping schemes-Gaussian apodization and matched filtering with triple
      resonance peaks-are proposed and numerically investigated under realistic
      experimental conditions: at the 50-cm-long AO interaction length of the fiber and
      at half of the original fiber diameter as the minimum thickness of the tailored
      fiber section. The results show that the highest peak of sidelobe spectra in
      filter transmission is suppressed from 11.64% to 0.54% via Gaussian modulation of
      the AO coupling coefficient (kappa). Matched filtering with triple resonance
      peaks operating with a single radio frequency signal is also achieved by cosine
      modulation of kappa, of which the modulation period determines the spectral
      distance between two satellite peaks located in both wings of the main resonance
      peak. The splitting of two satellite peaks in the filter spectra reaches 48.2 nm
      while the modulation period varies from 7.7 to 50 cm. The overall peak power of
      two satellite resonances is calculated to be 22% of the main resonance power. The
      results confirm the validity and practicality of our approach, and we predict
      robust and stable operation of the designed all-fiber torsional AO filters. 

PMID- 25608200
TI  - Measuring two-dimensional profiles of beam spots in a high-density spot array for
      a maskless lithography system.
AB  - We measure two-dimensional (2D) profiles of beam spots in a high-density spot
      array for a maskless lithography system. Since the size of each spot is
      comparable to that of a pixel in a charge-coupled device (CCD), we detect image
      frame data, which are the distribution of the intensity of the spot overlapped on
      the active area of the pixel in the CCD, by scanning with a nano-stage. Using the
      image frame data of the scanning CCD we determine reconstructed images of the
      beam spot array. We calculate the 2D profile of each spot by taking the
      deconvolution of the reconstructed image of the spot with the active area of the
      CCD pixel. We theoretically analyze the uncertainty in the measurement of
      profiles in terms of spot size for the variation of the scanning step of the nano
      stage and determine the step size to achieve uncertainty of less than 100 nm. We
      experimentally demonstrate the measurement of profiles of an 11*11 spot array for
      the proof of concept. Also, we analyze various parameters of the spot array, such
      as ellipticity, rotation of the spot profile, spot size, intensity distribution,
      and position. 

PMID- 25608201
TI  - Three-dimensional facial recognition using passive long-wavelength infrared
      polarimetric imaging.
AB  - We use a polarimetric camera to record the Stokes parameters and the degree of
      linear polarization of long-wavelength infrared radiation emitted by human faces.
      These Stokes images are combined with Fresnel relations to extract the surface
      normal at each pixel. Integrating over these surface normals yields a three
      dimensional facial image. One major difficulty of this technique is that the
      normal vectors determined from the polarizations are not unique. We overcome this
      problem by introducing an additional boundary condition on the subject. The major
      sources of error in producing inversions are noise in the images caused by
      scattering of the background signal and the ambiguity in determining the surface
      normals from the Fresnel coefficients. 

PMID- 25608202
TI  - Toward optical-tweezers-based force microscopy for airborne microparticles.
AB  - Optical tweezers have found widespread application in biological and colloidal
      physics for the measurement of pN forces over nanometer to micrometer length
      scales. Similar aerosol-phase measurements of interparticle force have not been
      reported in spite of the potential to better resolve particle coagulation
      kinetics. Various refractive index mismatches in the beam path as well as the
      need to explicitly account for gravity and inertial particle motion provide a
      number of challenges that must be overcome to make such measurements tractable.
      In this regard, we demonstrate schemes by which the particle position and trap
      stiffness may be unambiguously measured using bright-field microscopy with
      resolution comparable with analogous condensed-phase measurements. Moreover, some
      of the challenges of working with highly dynamic aqueous particles are introduced
      and exploited to observe size-dependent phenomena in aerosol optical tweezers.
      Notably, when combined with cavity-enhanced Raman spectroscopy, this provides a
      unique opportunity to explore trapping forces over a continuum of particle size
      and refractive index. It is expected that the methods developed will provide a
      basis for the measurement of pairwise interaction forces in aerosol optical
      tweezers while providing a probe of fundamental airborne particle trapping
      dynamics. 

PMID- 25608203
TI  - Gluing for Raman lidar systems using the lamp mapping technique.
AB  - In the context of combined analog and photon counting (PC) data acquisition in a
      Lidar system, glue coefficients are defined as constants used for converting an
      analog signal into a virtual PC signal. The coefficients are typically calculated
      using Lidar profile data taken under clear, nighttime conditions since, in the
      presence of clouds or high solar background, it is difficult to obtain accurate
      glue coefficients from Lidar backscattered data. Here we introduce a new method
      in which we use the lamp mapping technique (LMT) to determine glue coefficients
      in a manner that does not require atmospheric profiles to be acquired and permits
      accurate glue coefficients to be calculated when adequate Lidar profile data are
      not available. The LMT involves scanning a halogen lamp over the aperture of a
      Lidar receiver telescope such that the optical efficiency of the entire detection
      system is characterized. The studies shown here involve two Raman lidar systems;
      the first from Howard University and the second from NASA/Goddard Space Flight
      Center. The glue coefficients determined using the LMT and the Lidar
      backscattered method agreed within 1.2% for the water vapor channel and within
      2.5% for the nitrogen channel for both Lidar systems. We believe this to be the
      first instance of the use of laboratory techniques for determining the glue
      coefficients for Lidar data analysis. 

PMID- 25608204
TI  - GHz high power Yb-doped picosecond fiber laser and supercontinuum generation.
AB  - We demonstrated a 97 W all-fiber picosecond master oscillator power amplifier
      seeding by an actively harmonic mode-locked Yb-doped fiber laser. The laser seed
      pulse duration was 7.7 ps at a 1.223 GHz repetition rate with a central
      wavelength of 1062 nm. In addition, by launching the amplified pulses into a 5 m
      long photonic crystal fiber, we obtained a 41.8 W supercontinuum covering the
      wavelength from 600 to 1700 nm with a 10 dB bandwidth of 1040 nm. 

PMID- 25608205
TI  - Capability of long distance 100  GHz FMCW using a single GDD lamp sensor.
AB  - Millimeter wave (MMW)-based imaging systems are required for applications in
      medicine, homeland security, concealed weapon detection, and space technology.
      The lack of inexpensive room temperature imaging sensors makes it difficult to
      provide a suitable MMW system for many of the above applications. A 3D MMW
      imaging system based on chirp radar was studied previously using a scanning
      imaging system of a single detector. The radar system requires that the
      millimeter wave detector will be able to operate as a heterodyne detector. Since
      the source of radiation is a frequency modulated continuous wave (FMCW), the
      detected signal as a result of heterodyne detection gives the object's depth
      information according to value of difference frequency, in addition to the
      reflectance of the 2D image. New experiments show the capability of long distance
      FMCW detection by using a large scale Cassegrain projection system, described
      first (to our knowledge) in this paper. The system presents the capability to
      employ a long distance of at least 20 m with a low-cost plasma-based glow
      discharge detector (GDD) focal plane array (FPA). Each point on the object
      corresponds to a point in the image and includes the distance information. This
      will enable relatively inexpensive 3D MMW imaging. 

PMID- 25608206
TI  - Telescopic horizon scanning.
AB  - The problem of "distortionless" viewing with terrestrial telescopic systems
      (mainly "binoculars") remains problematic. The so called "globe effect" is only
      partially counteracted in modern designs. Theories addressing the phenomenon have
      never reached definitive closure. In this paper, we show that exact
      distortionless viewing with terrestrial telescopic systems is not possible in
      general, but that it is in principle possible in-very frequent in battle field
      and marine applications-the case of horizon scanning. However, this involves
      cylindrical optical elements. For opto-electronic systems, a full solution is
      more readily feasible. The solution involves a novel interpretation of the
      relevant constraints and objectives. For final design decisions, it is not
      necessary to rely on a corpus of psychophysical (or ergonomic) data, although one
      has to decide whether the instrument is intended as an extension of the eye or as
      a "pictorial" device. 

PMID- 25608207
TI  - High-power all-fiberized superfluorescent source with distributed side-coupled
      cladding-pumped fiber.
AB  - An all-fiberized broadband superfluorescent source based on a distributed side
      coupled cladding-pumped Yb-doped fiber is demonstrated. A recorded 102 W combined
      output power is obtained with the angle-cleaved output ends. The bandwidth is
      larger than 10 nm. The power scalability of the superfluorescent source is
      analyzed numerically. It is found that, besides the optical feedback, the active
      fiber length is another key. The result shows that, by optimizing the active
      fiber length, it is promising to realize a 600 W superfluorescent source with
      this scheme. 

PMID- 25608208
TI  - Visible Infrared Imaging Radiometer Suite solar diffuser calibration and its
      challenges using a solar diffuser stability monitor.
AB  - The reflective solar bands (RSB) of the Visible Infrared Imaging Radiometer Suite
      (VIIRS) on board the Suomi National Polar-orbiting Partnership (SNPP) satellite
      is calibrated by a solar diffuser (SD) whose performance is itself monitored by a
      solar diffuser stability monitor (SDSM). In this study, we describe the
      calibration algorithm of the SDSM, analyze the current two and a half years of
      calibration data, and derive the performance result for the SD, commonly called
      SD degradation or H-factors. The application of the newly derived vignetting
      functions for both the SD screen and the SDSM sun-view screen effectively removes
      the seasonal oscillations in the derived SD degradation and significantly
      improves the quality of the H-factors. The full illumination region, the so
      called "sweet spot," for both SD view and SDSM sun view is carefully examined and
      selected to ensure a consistent and an optimal number of valid data samples to
      reduce the sample noise owing to inconsistent or lack of samples. The result
      shows that SD degrades much faster at short wavelength as expected, about 28.5%
      at 412 nm but only 1.2% at 935 nm up to date. The performance of the SD degrades
      exponentially with time until 7 November 2013 but has since become flat. This
      sudden flattening of the SD degradation is a new phenomenon never previously
      observed for the degradations of the SD on VIIRS or other satellite sensors. The
      overall result shows that SDSM is essentially functioning without flaws in
      catching the on-orbit degradation of the SD. The most significant and direct
      impact of this work would be on the quality of the ocean color products that
      depend sensitively on moderate RSB (RSB) (M1-M8, M10, and M11). Two very
      important and key questions on the performance of the SD are also raised. One
      pertains to the directional dependence of the SD degradation result, and it is
      shown that the SD does not degrade uniformly in all directions as has been
      assumed by all SD calibration analyses. This has a definitive impact on the RSB
      calibration. Another is on the degradation of the SD at the shortwave infrared
      (SWIR) wavelengths, and it is shown that the zero degradation input for the RSB
      calibration would be erroneous. Last, the impact of the stray light on the SD
      since "first light" is cleanly exhibited in the improved SD degradation result. 

PMID- 25608209
TI  - Radiant exposure level comparison between Gaussian and top hat beams in various
      scanning patterns.
AB  - The radiant exposure of optical irradiation beams with different scanning
      parameters has been theoretically studied. We analyzed the difference in radiant
      exposure introduced by Gaussian and top hat beams. Various parameters such as
      scanning pattern, aperture position, beam size and scan spacing were also
      introduced in this study. We found that Gaussian beams introduce higher
      calculated radiant exposure to the aperture than top hat beams for certain beam
      size to aperture size ratios. However, as the scan spacing decreases, the radiant
      exposure difference calculated from Gaussian and top hat beams diminishes. 

PMID- 25608210
TI  - Influence of microemulsion-mucin interaction on the fate of microemulsions
      diffusing through pig gastric mucin solutions.
AB  - Mucus layer, a selective diffusion barrier, has an important effect on the fate
      of drug delivery systems in the gastrointestinal tract. To study the fate of
      microemulsions in the mucus layer, four microemulsion formulations with different
      particle sizes and lipid compositions were prepared. The microemulsion-mucin
      interaction was demonstrated by the fluorescence resonance energy transfer (FRET)
      method. Moreover, the microemulsions were observed aggregated into micron-sized
      emulsions by laser confocal microscopy. We concluded the microemulsion-mucin
      interaction not only led to microemulsions closely adhered to mucins but also
      destroyed the structure of microemulsions. At last, the diffusion of blank
      microemulsions and microemulsion-carried drugs (resveratrol and hymecromone)
      through mucin solutions was determined by the fluorescence recovery after
      photobleaching (FRAP) method and the Franz diffusion cell method. The results
      demonstrated the diffusion of microemulsions was significantly hindered by mucin
      solutions. The particle size of microemulsions had a negligible effect on the
      diffusion coefficients. However, the type of lipid played an important role,
      which could form hydrophobic interactions with mucins. Interestingly,
      microemulsion-carried drugs with different core/shell locations seemed to suffer
      different fates in the mucin solutions. The drug incorporated in the oil core of
      microemulsions, resveratrol, was transported through the mucus layer by the
      carriers, while the drug incorporated in the surfactant shell of microemulsions,
      hymecromone, was separated from the carriers and diffused toward the epithelium
      in the form of free molecules. 

PMID- 25608211
TI  - Double cluster heads model for secure and accurate data fusion in wireless sensor
      networks.
AB  - Secure and accurate data fusion is an important issue in wireless sensor networks
      (WSNs) and has been extensively researched in the literature. In this paper, by
      combining clustering techniques, reputation and trust systems, and data fusion
      algorithms, we propose a novel cluster-based data fusion model called Double
      Cluster Heads Model (DCHM) for secure and accurate data fusion in WSNs. Different
      from traditional clustering models in WSNs, two cluster heads are selected after
      clustering for each cluster based on the reputation and trust system and they
      perform data fusion independently of each other. Then, the results are sent to
      the base station where the dissimilarity coefficient is computed. If the
      dissimilarity coefficient of the two data fusion results exceeds the threshold
      preset by the users, the cluster heads will be added to blacklist, and the
      cluster heads must be reelected by the sensor nodes in a cluster. Meanwhile,
      feedback is sent from the base station to the reputation and trust system, which
      can help us to identify and delete the compromised sensor nodes in time. Through
      a series of extensive simulations, we found that the DCHM performed very well in
      data fusion security and accuracy. 

PMID- 25608212
TI  - Hyperspectral imagery super-resolution by compressive sensing inspired dictionary
      learning and spatial-spectral regularization.
AB  - Due to the instrumental and imaging optics limitations, it is difficult to
      acquire high spatial resolution hyperspectral imagery (HSI). Super-resolution
      (SR) imagery aims at inferring high quality images of a given scene from degraded
      versions of the same scene. This paper proposes a novel hyperspectral imagery
      super-resolution (HSI-SR) method via dictionary learning and spatial-spectral
      regularization. The main contributions of this paper are twofold. First, inspired
      by the compressive sensing (CS) framework, for learning the high resolution
      dictionary, we encourage stronger sparsity on image patches and promote smaller
      coherence between the learned dictionary and sensing matrix. Thus, a sparsity and
      incoherence restricted dictionary learning method is proposed to achieve higher
      efficiency sparse representation. Second, a variational regularization model
      combing a spatial sparsity regularization term and a new local spectral
      similarity preserving term is proposed to integrate the spectral and spatial
      contextual information of the HSI. Experimental results show that the proposed
      method can effectively recover spatial information and better preserve spectral
      information. The high spatial resolution HSI reconstructed by the proposed method
      outperforms reconstructed results by other well-known methods in terms of both
      objective measurements and visual evaluation. 

PMID- 25608213
TI  - A survey of online activity recognition using mobile phones.
AB  - Physical activity recognition using embedded sensors has enabled many context
      aware applications in different areas, such as healthcare. Initially, one or more
      dedicated wearable sensors were used for such applications. However, recently,
      many researchers started using mobile phones for this purpose, since these
      ubiquitous devices are equipped with various sensors, ranging from accelerometers
      to magnetic field sensors. In most of the current studies, sensor data collected
      for activity recognition are analyzed offline using machine learning tools.
      However, there is now a trend towards implementing activity recognition systems
      on these devices in an online manner, since modern mobile phones have become more
      powerful in terms of available resources, such as CPU, memory and battery. The
      research on offline activity recognition has been reviewed in several earlier
      studies in detail. However, work done on online activity recognition is still in
      its infancy and is yet to be reviewed. In this paper, we review the studies done
      so far that implement activity recognition systems on mobile phones and use only
      their on-board sensors. We discuss various aspects of these studies. Moreover, we
      discuss their limitations and present various recommendations for future
      research. 

PMID- 25608214
TI  - The enhanced formaldehyde-sensing properties of P3HT-ZnO hybrid thin film OTFT
      sensor and further insight into its stability.
AB  - A thin-film transistor (TFT) having an organic-inorganic hybrid thin film
      combines the advantage of TFT sensors and the enhanced sensing performance of
      hybrid materials. In this work, poly(3-hexylthiophene) (P3HT)-zinc oxide (ZnO)
      nanoparticles' hybrid thin film was fabricated by a spraying process as the
      active layer of TFT for the employment of a room temperature operated
      formaldehyde (HCHO) gas sensor. The effects of ZnO nanoparticles on morphological
      and compositional features, electronic and HCHO-sensing properties of P3HT-ZnO
      thin film were systematically investigated. The results showed that P3HT-ZnO
      hybrid thin film sensor exhibited considerable improvement of sensing response
      (more than two times) and reversibility compared to the pristine P3HT film
      sensor. An accumulation p-n heterojunction mechanism model was developed to
      understand the mechanism of enhanced sensing properties by incorporation of ZnO
      nanoparticles. X-ray photoelectron spectroscope (XPS) and atomic force microscopy
      (AFM) characterizations were used to investigate the stability of the sensor in
      depth, which reveals the performance deterioration was due to the changes of
      element composition and the chemical state of hybrid thin film surface induced by
      light and oxygen. Our study demonstrated that P3HT-ZnO hybrid thin film TFT
      sensor is beneficial in the advancement of novel room temperature HCHO sensing
      technology. 

PMID- 25608215
TI  - Sensor data security level estimation scheme for wireless sensor networks.
AB  - Due to their increasing dissemination, wireless sensor networks (WSNs) have
      become the target of more and more sophisticated attacks, even capable of
      circumventing both attack detection and prevention mechanisms. This may cause WSN
      users, who totally trust these security mechanisms, to think that a sensor
      reading is secure, even when an adversary has corrupted it. For that reason, a
      scheme capable of estimating the security level (SL) that these mechanisms
      provide to sensor data is needed, so that users can be aware of the actual
      security state of this data and can make better decisions on its use. However,
      existing security estimation schemes proposed for WSNs fully ignore detection
      mechanisms and analyze solely the security provided by prevention mechanisms. In
      this context, this work presents the sensor data security estimator (SDSE), a new
      comprehensive security estimation scheme for WSNs. SDSE is designed for
      estimating the sensor data security level based on security metrics that analyze
      both attack prevention and detection mechanisms. In order to validate our
      proposed scheme, we have carried out extensive simulations that show the high
      accuracy of SDSE estimates. 

PMID- 25608216
TI  - Integrated semantics service platform for the Internet of Things: a case study of
      a smart office.
AB  - The Internet of Things (IoT) allows machines and devices in the world to connect
      with each other and generate a huge amount of data, which has a great potential
      to provide useful knowledge across service domains. Combining the context of IoT
      with semantic technologies, we can build integrated semantic systems to support
      semantic interoperability. In this paper, we propose an integrated semantic
      service platform (ISSP) to support ontological models in various IoT-based
      service domains of a smart city. In particular, we address three main problems
      for providing integrated semantic services together with IoT systems: semantic
      discovery, dynamic semantic representation, and semantic data repository for IoT
      resources. To show the feasibility of the ISSP, we develop a prototype service
      for a smart office using the ISSP, which can provide a preset, personalized
      office environment by interpreting user text input via a smartphone. We also
      discuss a scenario to show how the ISSP-based method would help build a smart
      city, where services in each service domain can discover and exploit IoT
      resources that are wanted across domains. We expect that our method could
      eventually contribute to providing people in a smart city with more integrated,
      comprehensive services based on semantic interoperability. 

PMID- 25608217
TI  - Fast traffic sign recognition with a rotation invariant binary pattern based
      feature.
AB  - Robust and fast traffic sign recognition is very important but difficult for safe
      driving assistance systems. This study addresses fast and robust traffic sign
      recognition to enhance driving safety. The proposed method includes three stages.
      First, a typical Hough transformation is adopted to implement coarse-grained
      location of the candidate regions of traffic signs. Second, a RIBP (Rotation
      Invariant Binary Pattern) based feature in the affine and Gaussian space is
      proposed to reduce the time of traffic sign detection and achieve robust traffic
      sign detection in terms of scale, rotation, and illumination. Third, the
      techniques of ANN (Artificial Neutral Network) based feature dimension reduction
      and classification are designed to reduce the traffic sign recognition time.
      Compared with the current work, the experimental results in the public datasets
      show that this work achieves robustness in traffic sign recognition with
      comparable recognition accuracy and faster processing speed, including training
      speed and recognition speed. 

PMID- 25608218
TI  - An activity recognition model using inertial sensor nodes in a wireless sensor
      network for frozen shoulder rehabilitation exercises.
AB  - This paper proposes a model for recognizing motions performed during
      rehabilitation exercises for frozen shoulder conditions. The model consists of
      wearable wireless sensor network (WSN) inertial sensor nodes, which were
      developed for this study, and enables the ubiquitous measurement of bodily
      motions. The model employs the back propagation neural network (BPNN) algorithm
      to compute motion data that are formed in the WSN packets; herein, six types of
      rehabilitation exercises were recognized. The packets sent by each node are
      converted into six components of acceleration and angular velocity according to
      three axes. Motor features such as basic acceleration, angular velocity, and
      derivative tilt angle were input into the training procedure of the BPNN
      algorithm. In measurements of thirteen volunteers, the accelerations and included
      angles of nodes were adopted from possible features to demonstrate the procedure.
      Five exercises involving simple swinging and stretching movements were recognized
      with an accuracy of 85%-95%; however, the accuracy with which exercises entailing
      spiral rotations were recognized approximately 60%. Thus, a characteristic space
      and enveloped spectrum improving derivative features were suggested to enable
      identifying customized parameters. Finally, a real-time monitoring interface was
      developed for practical implementation. The proposed model can be applied in
      ubiquitous healthcare self-management to recognize rehabilitation exercises. 

PMID- 25608219
TI  -  De novo isolation of antibodies with pH-dependent binding properties.
AB  - pH-dependent antibodies are engineered to release their target at a slightly
      acidic pH, a property making them suitable for clinical as well as
      biotechnological applications. Such antibodies were previously obtained by
      histidine scanning of pre-existing antibodies, a labor-intensive strategy
      resulting in antibodies that displayed residual binding to their target at pH
      6.0. We report here the de novo isolation of pH-dependent antibodies selected by
      phage display from libraries enriched in histidines. Strongly pH-dependent clones
      with various affinity profiles against CXCL10 were isolated by this method. Our
      best candidate has nanomolar affinity for CXCL10 at pH 7.2, but no residual
      binding was detected at pH 6.0. We therefore propose that this new process is an
      efficient strategy to generate pH-dependent antibodies. 

PMID- 25608220
TI  - Lack of documentation of evidence-based prognostication in cancer patients by
      inpatient palliative care consultants.
AB  - BACKGROUND: Prognostication plays a key role in palliative care (PC). It is
      critical for advance care planning, determining hospice eligibility, and
      communication. In contrast to subjective clinical prognostication, evidence-based
      prognostication (EBP) uses existing validated data to quantify prognosis;
      however, the extent to which PC providers use EBP is limited. OBJECTIVE: The
      objective was to analyze documentation of EBP by PC providers in the absence of
      an inpatient consultation note template at a single academic medical center.
      METHODS: We retrospectively evaluated prognostic documentation of inpatient PC
      consultations on oncology patients at a single academic hospital. Ratings of
      Eastern Cooperative Oncology Group (ECOG) Scale, Karnofsky Performance Scale
      (KPS), Palliative Performance Scale, and/or activities of daily living (ADLs)
      were considered documentation of functional status. PC-specific documentation of
      EBP included the Palliative Prognostic Index and/or Palliative Prognostic Score.
      RESULTS: There were 412 inpatient PC consultations for oncology patients (2012
      2013). Reasons for consultation included goals of care (n=108), symptom
      management (n=181), or both (n=123). In the absence of a note template,
      functional status was documented in 6% (n=24) of consultation notes, while no
      consultation notes contained EBP documentation of the Palliative Prognostic Index
      and Palliative Prognostic Score. CONCLUSION: This retrospective analysis
      conducted at a single academic medical center suggests poor documentation by PC
      providers of EBP in the absence of a consultation note template. Research and
      educational opportunities exist to evaluate barriers to EBP utilization and
      documentation by PC providers.

PMID- 25608222
TI  - Spinal cord stimulation analgesia: substantiating the mechanisms for neuropathic
      pain treatment.

PMID- 25608221
TI  - Internalization and vacuolar targeting of the brassinosteroid hormone receptor
      BRI1 are regulated by ubiquitination.
AB  - Brassinosteroids are plant steroid hormones that control many aspects of plant
      growth and development, and are perceived at the cell surface by the plasma
      membrane-localized receptor kinase BRI1. Here we show that BRI1 is post
      translationally modified by K63 polyubiquitin chains in vivo. Using both
      artificial ubiquitination of BRI1 and generation of an ubiquitination-defective
      BRI1 mutant form, we demonstrate that ubiquitination promotes BRI1
      internalization from the cell surface and is essential for its recognition at the
      trans-Golgi network/early endosomes (TGN/EE) for vacuolar targeting. Finally, we
      demonstrate that the control of BRI1 protein dynamics by ubiquitination is an
      important control mechanism for brassinosteroid responses in plants. Altogether,
      our results identify ubiquitination and K63-linked polyubiquitin chain formation
      as a dual targeting signal for BRI1 internalization and sorting along the
      endocytic pathway, and highlight its role in hormonally controlled plant
      development. 

PMID- 25608223
TI  - Hepatitis C virus infection: a risk factor for Parkinson's disease.
AB  - Recent studies found that hepatitis C virus (HCV) may invade the central nervous
      system, and both HCV and Parkinson's disease (PD) have in common the
      overexpression of inflammatory biomarkers. We analysed data from a community
      based integrated screening programme based on a total of 62,276 subjects. We used
      logistic regression models to investigate association between HCV infection and
      PD. The neurotoxicity of HCV was evaluated in the midbrain neuron-glia coculture
      system in rats. The cytokine/chemokine array was performed to measure the
      differences of amounts of cytokines released from midbrain in the presence and
      absence of HCV. The crude odds ratios (ORs) for having PD were 0.62 [95%
      confidence interval (CI), 0.48-0.81] and 1.91 (95% CI, 1.48-2.47) for hepatitis B
      virus (HBV) and HCV. After controlling for potential confounders, the association
      between HCV and PD remained statistically significant (adjusted OR = 1.39; 95%
      CI, 1.07-1.80), but not significantly different between HBV and PD. The HCV
      induced 60% dopaminergic neuron death in the midbrain neuron-glia coculture
      system in rats, similar to that of 1-methyl-4-phenylpyridinium (MPP(+) ) but not
      caused by HBV. This link was further supported by the finding that HCV infection
      may release the inflammatory cytokines, which may play a role in the pathogenesis
      of PD. In conclusion, our study demonstrated a significantly positive
      epidemiological association between HCV infection and PD and corroborated the
      dopaminergic toxicity of HCV similar to that of MPP(+) .

PMID- 25608224
TI  - Overexpression of Aiolos in Nalm-6 acute lymphoblastic leukaemia cells reduces
      apoptosis by suppressing phosphatase and tensin homologue deleted on chromosome
      10 and activating the phosphatidylinositol-3-kinase/Akt signalling pathway.
AB  - The aim of the present study was to elucidate the molecular mechanism of Aiolos
      in the regulation of B-cell leukaemia. A lentiviral system was used for
      overexpression of the Aiolos gene in Nalm-6 cells to determine the effects of
      Aiolos on proliferation, apoptosis and the cell cycle. The expression and
      activation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and
      Akt were also investigated. Upregulation of Aiolos inhibited cell growth and
      arrested an increased number of Nalm-6 cells at the G0/G1 phase. The apoptotic
      cell quantities were also significantly lower in the Aiolos-transfected Nalm-6
      cells. In addition, Aiolos overexpression downregulated PTEN, but increased the
      expression and phosphorylation of Akt in the Nalm-6 cells. The Akt inhibitor,
      Akti-1/2, reduced the percentage of viable Aiolos-overexpressed Nalm-6 cells,
      however, it had no effect on cell cycle arrest or proliferation. Aiolos
      upregulation in the Nalm-6 cells inhibited cell proliferation, suppressed
      apoptosis and arrested the cell cycle at the G0/G1 phase. Aiolos improved the
      survival of Nalm-6 cells via PTEN- and Akt-dependent processes.

PMID- 25608225
TI  - Interplay of weak interactions in the atom-by-atom condensation of xenon within
      quantum boxes.
AB  - Condensation processes are of key importance in nature and play a fundamental
      role in chemistry and physics. Owing to size effects at the nanoscale, it is
      conceptually desired to experimentally probe the dependence of condensate
      structure on the number of constituents one by one. Here we present an approach
      to study a condensation process atom-by-atom with the scanning tunnelling
      microscope, which provides a direct real-space access with atomic precision to
      the aggregates formed in atomically defined 'quantum boxes'. Our analysis reveals
      the subtle interplay of competing directional and nondirectional interactions in
      the emergence of structure and provides unprecedented input for the structural
      comparison with quantum mechanical models. This approach focuses on-but is not
      limited to-the model case of xenon condensation and goes significantly beyond the
      well-established statistical size analysis of clusters in atomic or molecular
      beams by mass spectrometry. 

PMID- 25608226
TI  - Benign recurrent sixth nerve palsy in an infant.
AB  - Acquired sixth nerve palsies in children are rare and may indicate serious
      underlying pathologies such as tumors, trauma, or raised intracranial pressure. A
      case of an infant with three episodes of benign sixth nerve palsy is presented.

PMID- 25608227
TI  - Sixth cranial nerve palsy due to arachnoid cyst.
AB  - Sixth cranial nerve palsy is an extremely rare complication of an arachnoid cyst.
      A 4-year-old boy who presented with left abducens palsy and a subdural hygroma
      complicating arachnoid cyst is discussed. Comprehensive review of the world
      literature revealed only 12 additional cases.

PMID- 25608228
TI  - Recurrent ocular involvement in pediatric atypical hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (HUS) is a subtype of thrombotic
      microangiopathy associated with complement alternative pathway dysregulation. It
      is clinically characterized by a relapsing course and a poor prognosis. Multiple
      organ systems are commonly affected by thrombotic microangiopathy in pediatric
      atypical HUS; however, ocular involvement is rarely reported. The case of an 11
      year-old girl diagnosed as having atypical HUS who presented with bilateral
      central retinal vein occlusions with macular subhyaloid hemorrhage during her
      initial onset and ophthalmoplegia, diplopia, and optic disc edema during her
      relapsing episode 1 year later is described. All ocular manifestations occurred
      in the convalescence phase of atypical HUS. No other extrarenal complications
      were found and full recovery was achieved following typical treatment for
      atypical HUS (ie, plasma infusion, steroid, and supportive therapy). This is
      thought to be the first reported case of recurrent ocular involvement in
      pediatric atypical HUS.

PMID- 25608229
TI  - ESCI award lecture: regulation, function and biomarker potential of DNA
      methylation.
AB  - Methylation of DNA and modifications of histones have emerged as intricately
      involved in gene regulation as they cross-talk and respond in multiple ways to
      the activity of transcription factors. Measuring these epigenome components has
      become a powerful tool to identify regulatory principles and biomarkers that
      predict cellular state during development or disease. Here, I will focus on DNA
      methylation as a reversible epigenetic modification of DNA that has been studied
      in great detail at the level of the genome. Recent advances in sequencing have
      identified unexpected dynamics of this modification, which are tightly linked to
      gene regulation. Understanding how DNA methylation patterns are read and how they
      contribute to regulation will be critical to interpret and utilize genomic maps
      of DNA methylation. As these patterns are dynamic during cellular differentiation
      and perturbed in disease, they present an opportunity to use DNA methylation as a
      biomarker. 

PMID- 25608232
TI  - C-terminus of Sororin interacts with SA2 and regulates sister chromatid cohesion.
AB  - Sororin is a conserved protein required for accurate separation of sister
      chromatids in each cell cycle. Sororin is recruited to chromatin during DNA
      replication, protects sister chromatid cohesion in S and G2 phase, and regulates
      the resolution of sister chromatid cohesion in mitosis. Sororin binds to cohesin
      complex, but how Sororin and cohesin subunits interact remains unclear. Here we
      report that the C-terminus of Sororin, especially the last 12 amino acid (aa)
      residues, is important for Sororin to bind cohesin core subunit SA2. Deletion of
      the last 12aa residues not only inhibits the interactions between Sororin and SA2
      but also causes precocious chromosome separation. Our data suggest that the C
      terminus of Sororin functions as an anchor binding to SA2, which facilitates
      other conserved motifs on Sororin to interact with other proteins to regulate
      sister chromatid cohesion and separation.

PMID- 25608233
TI  - Environmental concerns of roxarsone in broiler poultry feed and litter in
      Maryland, USA.
AB  - Roxarsone has been used extensively in the broiler chicken industry. We reviewed
      the environmental concerns of this usage. To summarize, arsenic added to poultry
      feed as roxarsone ends up in poultry litter. Fresh litter contains predominately
      roxarsone, whereas aged litter contains predominately inorganic arsenic. Soil
      arsenic concentrations from long-term poultry litter applications can exceed
      Maryland arsenic soil background remediation standards. Due to continued soil
      accumulation, arsenic-amended litter use as fertilizer is thought to be
      unsustainable. Surface-applied roxarsone-amended litter does not influence deep
      aquifer arsenic concentrations but is transported as inorganic arsenic to
      receiving waters and very shallow groundwater after precipitation. Arsenic in
      some receiving waters and sediments from agriculturally dominated watersheds have
      levels above established criteria. Arsenic in fish and shellfish is mostly
      organic. Phosphorus-based nutrient management will tend to limit PL application
      rates in areas that have over-applied phosphorus relative to crop needs,
      resulting in decreased rates of arsenic application and accumulation. Despite
      most arsenic in surface soils being tightly bound, as surface soils become more
      enriched in arsenic, the potential for downward movement increases but is limited
      in most soils due to the high capacity for binding of arsenic to clay minerals
      and oxides of iron and aluminum in subsoil horizons. In 2012, Maryland passed a
      law banning the use of arsenic additives except nitarsone in poultry feed. In
      2013, the USFDA withdrew approval of roxarsone, carbarsone, and arsanilic but is
      reviewing nitarsone. 

PMID- 25608234
TI  - Contact angle of a nanodrop on a nanorough solid surface.
AB  - The contact angle of a cylindrical nanodrop on a nanorough solid surface is
      calculated, for both hydrophobic and hydrophilic surfaces, using the density
      functional theory. The emphasis of the paper is on the dependence of the contact
      angle on roughness. The roughness is modeled by rectangular pillars of infinite
      length located on the smooth surface of a substrate, with fluid-pillar
      interactions different in strength from the fluid-substrate ones. It is shown
      that for hydrophobic substrates the trend of the contact angle to increase with
      increasing roughness, which was noted in all previous studies, is not universally
      valid, but depends on the fluid-pillar interactions, pillar height, interpillar
      distance, as well as on the size of the drop. For hydrophilic substrate, an
      unusual kink-like dependence of the contact angle on the nanodrop size is found
      which is caused by the change in the location of the leading edges of the
      nanodrop on the surface. It is also shown that the Wenzel and Cassie-Baxter
      equations can not explain all the peculiarities of the contact angle of a
      nanodrop on a nanorough surface. 

PMID- 25608235
TI  - Seeking fluid possibility and solid ground: space and movement in mental health
      service users' experiences of 'crisis'.
AB  - Since the closure of the UK asylums, 'the community' has become short hand for
      describing a variety of disparate and complex spaces, in which service users
      manage their experiences of distress. An examination of such spaces here forms
      the basis of an analysis of the way in which service users move through and
      within space, to establish agency and dis/order while distressed. Seventeen
      participants, with various experiences of mental distress took part in a
      qualitative study, and a further textual analysis was conducted on eight
      published autobiographies. In the context of the interviews, participants
      presented drawings of the spaces they occupy during times of crisis, wellbeing
      and recovery. All texts were analysed using a thematic approach, informed by
      theories of embodiment and relational space. In this paper, the focus is directed
      towards two key patterns of movement, in order to explore ways in which
      participants experiencing various forms of mental health crisis used space in
      order to maintain and manage feelings of agency. Firstly, incidents where
      participants described moving towards fluid, outside spaces are explored, with
      agency being established through seeking, and utilising, greater possibilities
      for action and engaging others. In addition, the opposite pattern of movement is
      also explored, using incidents where participants described moving indoors, using
      the private space of the home to establish order and restore feelings of agency
      and strength, in contrast to overwhelming experiences in public space.
      Connections between these patterns of movement and particular forms of distress
      are discussed. It is argued that community and private spaces are integral to the
      ways in which selfhood, agency and action is experienced in mental distress,
      which in turn has implications for policy, treatment and community action. 

PMID- 25608236
TI  - One-dimensional lanthanide coordination polymers: synthesis, structures, and
      single-ion magnetic behaviour.
AB  - A family of isostructural one-dimensional (1D) lanthanide compounds with the
      formula [Ln(III)(L)(NO3)(DMF)2]infinity, where Ln = Tb (1), Dy (2), Ho (3) and Er
      (4), was synthesised and structurally characterised. The magnetic behaviour of
      these compounds is demonstrated, and their static and dynamic properties are
      discussed and analyzed. The results of dc magnetic susceptibility measurements
      regarding compounds 1-4 indicate the existence of thermal depopulation of the
      crystal field-induced splitting of mJ levels of Ln ions, while the observed
      frequency-dependent out-of-phase ac magnetic susceptibility signals under certain
      magnetic fields for compounds 1, 2, and 4 show a slow relaxation of the
      magnetisation with an energy barrier of 6.15, 54.45, and 28.14 K, respectively.
      Also, complex 2 shows peak maxima of chiM'' signals in temperature-dependent as
      well as frequency-dependent ac magnetic susceptibility measurements under an
      appropriate magnetic field, indicating that the relaxation process is dominantly
      thermally activated.

PMID- 25608237
TI  - Plasma levels and placental expression of vaspin in pregnant women with diabetes
      mellitus.
AB  - The present study aimed to investigate visceral adipose tissue-specific serpin
      (vaspin) concentrations in serum and term placentas and relate these values to
      insulin resistance and lipid parameters in women with gestational diabetes
      mellitus (GDM). A total of 30 GDM subjects and 27 age-matched pregnant women with
      normal glucose tolerance (NGT, control) were included. Serum glucose, glycated
      hemoglobin (HbA1c), lipid profile, insulin, and vaspin were measured at the end
      of pregnancy, and homeostasis model of assessment-insulin resistance (HOMA-IR)
      values were calculated. Vaspin mRNA and protein levels in placentas were measured
      by real-time fluorescence quantitative reverse transcription polymerase chain
      reaction (RT-qPCR) and Western blotting, respectively. Serum vaspin levels were
      significantly lower in the GDM group than in controls (0.49 +/- 0.24 vs 0.83 +/-
      0.27 ng/mL, respectively; P<0.01). Three days after delivery, serum vaspin levels
      were significantly decreased in subjects with GDM (0.36 +/- 0.13 vs 0.49 +/- 0.24
      ng/mL, P<0.01). However, in the GDM group, serum vaspin levels were not
      correlated with the parameters evaluated. In contrast, in the control group,
      serum vaspin levels were positively correlated with triglycerides (TG; r=0.45,
      P=0.02) and very low-density lipoprotein cholesterol (VLDL-C; r=0.42, P=0.03).
      Placental mRNA vaspin (0.60 +/- 0.32 vs 0.68 +/- 0.32, P=0.46) and protein (0.30
      +/- 0.08 vs 0.39 +/- 0.26; P=0.33) levels in the GDM group did not differ
      significantly from those in the control group, but were negatively correlated
      with neonatal birth weight in the GDM group (r=-0.48, P=0.03; r=-0.88; P<0.01).
      Our findings indicated that vaspin may be an important adipokine involved in
      carbohydrate and lipid metabolism and may also play a role in fetal development.

PMID- 25608238
TI  - Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone
      marrow microenvironment of patients with myelodysplastic syndromes.
AB  - The purpose of this study was to explore cytokine expression patterns and
      cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow
      microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone
      marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy
      donors (control group). The expression pattern of cytokines was detected by
      customized protein array. The karyotypes of MSCs were analyzed using fluorescence
      in situ hybridization. Compared with the control group, leukemia inhibitory
      factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone
      morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and
      transforming growth factor-beta in the MDS group were significantly downregulated
      (P<0.05), while interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha), and programmed death ligand (B7-H1) were significantly upregulated
      (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal
      karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in
      the control group. In conclusion, the up- and downregulated expression of these
      cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and
      SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-gamma, TNF-alpha,
      and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In
      addition, the abnormal karyotypes might be actively involved in the pathogenesis
      of MDS. Further studies are required to determine the role of abnormal karyotypes
      in the occurrence and development of MDS.

PMID- 25608239
TI  - Galactose oxidation using (13)C in healthy and galactosemic children.
AB  - Galactosemia is an inborn error of galactose metabolism that occurs mainly as the
      outcome of galactose-1-phosphate uridyltransferase (GALT) deficiency. The ability
      to assess galactose oxidation following administration of a galactose-labeled
      isotope (1-(13)C-galactose) allows the determination of galactose metabolism in a
      practical manner. We aimed to assess the level of galactose oxidation in both
      healthy and galactosemic Brazilian children. Twenty-one healthy children and
      seven children with galactosemia ranging from 1 to 7 years of age were studied. A
      breath test was used to quantitate (13)CO2 enrichment in exhaled air before and
      at 30, 60, and 120 min after the oral administration of 7 mg/kg of an aqueous
      solution of 1-(13)C-galactose to all children. The molar ratios of (13)CO2 and
      (12)CO2 were quantified by the mass/charge ratio (m/z) of stable isotopes in each
      air sample by gas-isotope-ratio mass spectrometry. In sick children, the
      cumulative percentage of (13)C from labeled galactose (CUMPCD) in the exhaled air
      ranged from 0.03% at 30 min to 1.67% at 120 min. In contrast, healthy subjects
      showed a much broader range in CUMPCD, with values from 0.4% at 30 min to 5.58%
      at 120 min. The study found a significant difference in galactose oxidation
      between children with and without galactosemia, demonstrating that the breath
      test is useful in discriminating children with GALT deficiencies.

PMID- 25608240
TI  - A systematic review of cross-cultural adaptation of the neck disability index.
AB  - STUDY DESIGN: Systematic review of cross-cultural adaptation. OBJECTIVE: To
      perform a systematic review of cross-cultural adaptations of the Neck Disability
      Index (NDI) and to give a critical assessment to improve its translation. SUMMARY
      OF BACKGROUND DATA: The NDI is used to assess functional capacity and physical
      activity in patients with neck pain, but the quality of its cross-cultural
      adaptations has not been systematically reviewed. METHODS: PubMed, Cochrane
      Library, and EMBASE were searched up through 2013 to identify studies of cross
      cultural NDI adaptations. Search terms were "Neck Disability Index" or "NDI" and
      "cross-cultur*" or "cultur*" or "valid*" or "equivalence" or "transl*." Data were
      extracted and study quality was assessed. RESULTS: Twenty-four different NDI
      versions were identified from 14 different languages/cultures. Most reported
      forward and back translation and pretesting, but sample size was a problem for
      most studies. The Cronbach alpha was generally acceptable, and 13 versions met
      the criterion of reliability by reporting an intraclass correlation coefficient
      of 0.70 or more, although some versions did not reach the minimal intraclass
      correlation coefficient. Eleven versions tested ceiling and floor effects, but
      only 1 Japanese version reported a floor effect. No study reported
      interpretability, and none provided the minimal important change or minimal
      important difference. CONCLUSION: The Arabic, Italian, and Thai versions were of
      higher quality than the other versions according to the overall assessment of the
      3 checklists. The Catalan, Chinese, Japanese, Korean, Thai, and Turkish versions
      need more research according to the Quality Criteria for Psychometric Properties
      of Health Status Questionnaire. Pretest sample size was not large enough in most
      cases. LEVEL OF EVIDENCE: 1.

PMID- 25608241
TI  - Reducing surgical site infection in spinal surgery with betadine irrigation and
      intrawound vancomycin powder.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: The objective of this study was
      to evaluate the efficacy of a surgical site infection (SSI) prevention protocol
      instituted in the Orthopaedic Spine Department at our institution. SUMMARY OF
      BACKGROUND DATA: SSI is an undesired complication of orthopedic spine surgical
      procedures. It poses a significant risk to the patient, as well as a financial
      toll on the health care system. A wide range of prophylactic measures have been
      used to attempt to reduce SSI rates. METHODS: A protocol consisting of a
      combination of 0.3% Betadine wound irrigation and 1 g of intrawound Vancomycin
      powder application was developed at our institution. Multiple data sources were
      consolidated for thorough evaluation of changes in SSI rates, patient risk
      factors, and changes in bacteriology. Identification of risk factors that
      predispose patients to SSI was performed using mixed-effects logistic regression
      in a univariate fashion. Risk factors with P values of 0.05 or less in univariate
      analysis were included together in a multivariate mixed-effects logistic
      regression model. RESULTS: SSI rates were reduced by 50% after the intervention;
      chi analysis comparing the SSI rates between the pre- and postintervention
      periods yielded a P value of 0.042. Rates of methicillin-resistant Staphylococcus
      aureus dropped from 30% to 7% and the rates of multibacterial infections dropped
      from 37% to 27%. The risk factors that were statistically significant in
      multivariate analysis were the following: age (odds ratio [OR] = 0.93), anemia
      (OR = 30.73), prior operation (OR = 27.45), and vertebral fracture (OR = 22.22).
      CONCLUSION: The combination of Betadine wound irrigation and intrawound
      vancomycin powder application led to both a clinically and statistically
      significant decrease in SSI rates by 50%. Bacteriology analysis and risk factor
      assessment proved to be valuable tools in assessing the efficacy of a new
      prophylactic measure and in the planning of future protocols. LEVEL OF EVIDENCE:
      4.

PMID- 25608243
TI  - Implant distribution in surgically instrumented Lenke 1 adolescent idiopathic
      scoliosis: does it affect curve correction?
AB  - STUDY DESIGN: Retrospective review of prospective multicenter database of
      patients with adolescent idiopathic scoliosis who underwent posterior spinal
      fusion. OBJECTIVE: To analyze implant distribution in surgically instrumented
      Lenke 1 patients and evaluate how it impacts curve correction. SUMMARY OF
      BACKGROUND DATA: Although pedicle screw constructs have demonstrated successful
      surgical results, the optimal pedicle screw density and configuration remain
      unclear. METHODS: A total of 279 patients with adolescent idiopathic scoliosis
      treated with pedicle screws were reviewed. Implant density was computed for each
      side of the instrumented segment, which was divided into 5 regions: distal and
      proximal ends (upper/lower instrumented vertebra +1 adjacent vertebra), apical
      region (apex +/- 1 vertebra), and the 2 regions in between (upper/lower
      periapical). Centralized measurement of Cobb angle and thoracic kyphosis was
      performed on preoperative and at 1-year postoperative radiographs as well as
      percent curve flexibility. RESULTS: The mean implant density was 1.66 implants
      per level fused (1.08 to 2) with greater available pedicles filled on the
      concavity (92%, 53%-100%) compared with the convex side (73%, 23%-100%, P <
      0.01). The concave distal end region had the highest density with 99% of pedicles
      filled (P < 0.01), followed by the other concave regions and the convex distal
      end region (88%-94%) (P > 0.05). Other convex regions of the construct had less
      instrumentation, with only 54% to 78% of pedicles instrumented (P < 0.01).
      Implant density in the concave apical region (69%, 23%-100%) had a positive
      effect on curve correction (P = 0.002, R = 0.19). CONCLUSION: Significant
      variability exists in implant distribution with the greatest variation on the
      convex side and lowest implant density used in the periapical convex regions.
      Only instrumentation at the concave side, particularly at the apical region, was
      associated with curve correction. This suggests that for a low implant density
      construct, the best regions for planned screw dropout may be in the periapical
      convexity. LEVEL OF EVIDENCE: 3.

PMID- 25608244
TI  - Hoffmann sign: clinical correlation of neurological imaging findings in the
      cervical spine and brain.
AB  - STUDY DESIGN: Retrospective validity study. OBJECTIVE: To investigate the
      relationship between Hoffmann sign and radiographical evidence of cervical spinal
      cord compression and brain lesions. SUMMARY OF BACKGROUND DATA: Clinical
      significance of Hoffmann sign remains controversial with conflicting reports
      regarding its sensitivity and specificity and its usefulness. METHODS: Patients
      were divided into 2 groups according to the presence of Hoffmann sign on physical
      examination. Imaging studies were blindly examined by 2 observers for possible
      cervical and brain lesions. The sensitivity, specificity, positive predictive
      value, negative predictive value, as well as accuracy for Hoffmann sign as it
      relates to cervical spinal cord compression and brain pathology, were calculated.
      RESULTS: Of the 91 patients with a positive Hoffmann sign, 32 (35%) showed severe
      cervical cord compression and/or myelomalacia. Forty-seven of these patients had
      brain imaging studies, and 5 (10%) had positive findings. There were 80 patients
      in the negative Hoffmann sign or control group. Twenty-one (27%) of them had
      severe cervical cord compression and/or myelomalacia. Twenty-three of these
      control patients underwent neurological imaging of the brain, and 2 (8%) had
      positive findings. Hoffmann sign was found to have 59% sensitivity, 49%
      specificity, 35% positive predictive value, and 72% negative predictive value for
      cervical cord compression. For brain pathology, sensitivity was 71%, specificity
      33%, positive predictive value 10%, and negative predictive value 95%.
      CONCLUSION: Hoffmann sign has too low a positive predictive value to be relied
      upon as a stand-alone physical examination finding and is not a reliable
      screening tool for solely predicting the presence of cervical spinal cord
      compression or brain pathology. LEVEL OF EVIDENCE: 2.

PMID- 25608245
TI  - Abdominal aortic injury during vertebroplasty.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe an intraoperative complication
      occurring from abdominal aortic penetration during a vertebroplasty procedure for
      vertebral fractures on Th12 and L1. SUMMARY OF BACKGROUND DATA: A vertebroplasty
      is a minimally invasive and widely performed procedure in elderly and high-risk
      patients, although there is a risk of life-threatening complications including
      aortic injury. However, little is known about the treatment of iatrogenic aortic
      penetration occurring during a vertebroplasty. METHODS: An 80-year-old female
      underwent a scheduled vertebroplasty procedure. When the needle was advanced into
      the L1 vertebral body, arterial blood spurted out from the needle hub and
      fluoroscopic imaging revealed penetration of the aorta. To minimize bleeding, we
      depressed blood pressure and kept the needle in place. While vital signs were
      maintained, we prepared for blood transfusion and circulation monitoring and
      consulted a cardiothoracic surgeon and a cardiologist. Contrast medium injected
      via the needle revealed that a hematoma had formed to shift the aortic wall
      beyond the needle. Circulation was stable while pressure of the needle decreased,
      thus the hematoma was thought to have become coagulated and the needle was
      cautiously withdrawn. RESULTS: After placing the patient in a supine position,
      aortic angiography revealed no leakage around the aorta and she was transferred
      to the intensive care unit. On postoperative day 1, no leakage around the aorta
      was confirmed on computed tomographic scans and the patient was extubated. During
      the 2-year follow-up period, no arterial complication was observed. CONCLUSION:
      Conservative treatment is optional for accidental aortic penetration during a
      vertebroplasty when a tamponade effect is expected. In cases with circulatory
      collapse, when the tamponade effect seems insufficient or a free wall rupture is
      suspected, prompt removal of the needle and surgical repair should be considered.
      LEVEL OF EVIDENCE: 5.

PMID- 25608246
TI  - Comparing cost-effectiveness of X-Stop with minimally invasive decompression in
      lumbar spinal stenosis: a randomized controlled trial.
AB  - STUDY DESIGN: Randomized clinical trial with 2-year follow-up. OBJECTIVE: To
      compare the cost-effectiveness of X-stop to minimally invasive decompression in
      patients with symptomatic lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA:
      Lumbar spinal stenosis is the most common indication for operative treatment in
      elderly. Although surgery is more costly than nonoperative treatment, health
      outcomes for more than 2 years were shown to be significantly better. Surgical
      treatment with minimally invasive decompression is widely used. X-stop is
      introduced as another minimally invasive technique showing good results compared
      with nonoperative treatment. METHODS: We enrolled 96 patients aged 50 to 85
      years, with symptoms of neurogenic intermittent claudication within 250-m walking
      distance and 1- or 2-level lumbar spinal stenosis, randomized to either minimally
      invasive decompression or X-stop. Quality-adjusted life-years were based on
      EuroQol EQ-5D. The hospital unit costs were estimated by means of the top-down
      approach. Each cost unit was converted into a monetary value by dividing the
      overall cost by the amount of cost units produced. The analysis of costs and
      health outcomes is presented by the incremental cost-effectiveness ratio.
      RESULTS: The study was terminated after a midway interim analysis because of
      significantly higher reoperation rate in the X-stop group (33%). The incremental
      cost for X-stop compared with minimally invasive decompression was &OV0556;2832
      (95% confidence interval: 1886-3778), whereas the incremental health gain was
      0.11 quality-adjusted life-year (95% confidence interval: -0.01 to 0.23). Based
      on the incremental cost and effect, the incremental cost-effectiveness ratio was
      &OV0556;25,700. CONCLUSION: The majority of the bootstrap samples displayed in
      the northeast corner of the cost-effectiveness plane, giving a 50% likelihood
      that X-stop is cost-effective at the extra cost of &OV0556;25,700 (incremental
      cost-effectiveness ratio) for a quality-adjusted life-year. The significantly
      higher cost of X-stop is mainly due to implant cost and the significantly higher
      reoperation rate. LEVEL OF EVIDENCE: 2.

PMID- 25608247
TI  - Pre- and postoperative photographs and surgical outcomes in patients with Lenke
      type 1 adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Clinical study with pre- and postoperative back photographs and
      postoperative Scoliosis Research Society-22 survey in patients who had undergone
      surgery for idiopathic scoliosis. OBJECTIVE: To determine the effect of showing
      patients their photographs before and after surgery for idiopathic scoliosis on
      postoperative patient satisfaction. SUMMARY OF BACKGROUND DATA: After scoliosis
      surgery, patient satisfaction may be limited because the patients cannot directly
      see their back and may forget the preoperative appearance. METHODS: In 60
      patients who had undergone surgery for correction of idiopathic scoliosis (Lenke
      type 1), pre- and postoperative photographs were taken from the anterior,
      posterior, and right and left lateral views. After surgery, patients in group 1
      (30 patients) were shown the preoperative and most recent follow-up photographs,
      and patients in group 2 (30 patients) had routine evaluation but were not shown
      their photographs. All patients completed the Scoliosis Research Society-22
      survey. RESULTS: Patients in both groups had similar age, sex, distribution of
      Lenke type and Risser sign, follow-up, and pre- and postoperative Cobb angles and
      balance (coronal and sagittal). A significant difference was observed between the
      groups for survey question 10 (which was about self-image), question 18 (which
      was about function and activity), and question 21 (which was about satisfaction)
      (P <= 0.05). There were no differences between patients in groups 1 and 2 in
      Scoliosis Research Society-22 domain or total scores. CONCLUSION: By showing
      patients the pre- and postoperative clinical photographs, patient satisfaction
      may be greater, as measured with some SRS-22 scores. This method may enable
      clinicians to positively change the patients' self-image perception after surgery
      for correction of scoliosis. LEVEL OF EVIDENCE: 4.

PMID- 25608248
TI  - Acute cauda equina syndrome caused by a disk lesion: is emergent surgery the
      correct option?

PMID- 25608249
TI  - A biodegradable glue for annulus closure: evaluation of strength and endurance.
AB  - STUDY DESIGN: A biodegradable glue was biomechanically tested for annulus closure
      using nondegenerated goat intervertebral discs. Ultimate strength and endurance
      tests were performed using native and punctured discs as positive and negative
      controls, respectively. OBJECTIVE: The aim of this study was to investigate the
      feasibility and biomechanical properties of a biodegradable glue for annulus
      closure. SUMMARY OF BACKGROUND DATA: There is an unmet clinical need for annulus
      closure techniques. Isocyanate-terminated tissue glues show potential because
      they adhere to annulus tissue, have an elastic modulus similar to the annulus,
      and show limited cytotoxicity to human annulus fibrosus cells. METHODS: Three
      biomechanical tests were performed divided in 2 parts: part 1: ultimate strength
      tests comparing native, punctured (2.4-mm needle), and glued caprine
      intervertebral discs (n = 11 per group); part 2: 10 discs per group were
      subjected to a 10-day ex vivo endurance test of 864,000 load cycles, followed by
      ultimate strength tests. Outcome parameters include the restoration of strength
      after puncture, reduction of herniation in the endurance test, and conservation
      of glue strength after endurance testing. RESULTS: Part 1: The glue partially
      restored subsidence to failure and yield strength/ultimate strength ratio of
      intervertebral discs. Part 2: During endurance testing, 40% of punctured discs
      failed compared with none of the glued discs. Endurance testing did not affect
      glue strength, and pooling of ultimate strength tests showed that the glue
      restored ultimate strength, work to failure, and yield strength/ultimate strength
      to 79%, 75%, and 119% of native values, respectively. CONCLUSION: A biodegradable
      isocyanate-terminated glue increases the force at which nucleus protrusion
      occurs, and it limits herniations during endurance or ultimate strength tests.
      Biomechanical tests in a bioreactor provide a low-cost assessment for annulus
      repair strategies; however, the clinical efficacy needs to be further addressed
      using long-term in vivo studies. LEVEL OF EVIDENCE: N/A.

PMID- 25608250
TI  - Pathology of the adnexal mass.
AB  - An "adnexal mass" is a common specimen encountered in the daily pathology
      practice. Although most are benign, the incidence of malignancy increases with
      age, and approximately 30% are malignant in postmenopausal females. Herein we
      describe the salient macroscopic and microscopic features of the most prevalent
      adnexal masses. The entities are separated based on patients' age into
      premenopausal and postmenopausal, with further subdivision into non-neoplastic
      lesions, benign and malignant neoplasms, and those of uncertain behavior. For
      each entity, a brief differential diagnosis is discussed and for the malignant
      neoplasms, tables highlighting the key immunohistochemical differences that may
      be helpful are provided. 

PMID- 25608251
TI  - Imaging of the adnexal mass.
AB  - Imaging plays a central role in the diagnosis of adnexal masses, from the initial
      detection to characterization. Although ultrasound is often the first-line
      imaging modality in patients with adnexal masses, magnetic resonance imaging,
      computed tomography, and sometimes positron emission tomography-computed
      tomography are used for further evaluation. This chapter discusses the role of
      different imaging modalities in the evaluation of adnexal lesions as well as
      provides a summary of key imaging findings of common adnexal lesions. 

PMID- 25608252
TI  - Adnexal masses in the premenopausal patient.
AB  - Practitioners may frequently encounter adnexal masses in premenopausal women.
      Adnexal masses can represent a wide variety of etiologies, and therefore they can
      represent a diagnostic dilemma. When an adnexal mass is found the initial work up
      must focus on identifying acute pathology followed by determining the risk of a
      malignancy. Pelvic ultrasound remains the mainstay for evaluation of adnexal
      masses in premenopausal patients. If ultrasounds findings are indeterminate
      magnetic resonance imaging (MRI) is the next imaging modality of choice. The
      evaluation for malignancy should include serum marker screening. Aspiration of
      adnexal masses is generally avoided, due to the lack of therapeutic benefit and
      risk of seeding a tumor. When ultrasound findings are suggestive of benign
      disease, conservative management, including repeat imaging, should be considered.
      If the clinical suspicion for malignancy is high referral to a gynecologic
      oncologist is warranted. In other patients whom the evaluation of their adnexal
      mass remains unclear surgical excision with care not to disrupt the integrity of
      the mass should be performed for pathologic diagnosis. 

PMID- 25608253
TI  - Role of minimally invasive surgery in the management of adnexal masses.
AB  - Adnexal masses are common in women of all ages, and up to 10% of these women will
      undergo surgical removal of an ovarian mass. Laparoscopy is increasingly being
      viewed as the preferred surgical approach for management of these masses.
      Contraindications to laparoscopy are few, and multiple studies have shown
      benefits over laparotomy with respect to length of hospital stay, complications,
      and pain. Minimally invasive surgery can safely be performed by appropriately
      trained surgeons in almost all patient populations, including pregnancy and the
      morbidly obese. 

PMID- 25608254
TI  - Dermatologic disorders.

PMID- 25608255
TI  - Lichen sclerosus and lichen planus in women and girls.
AB  - Lichen planus and lichen sclerosus are common, chronic inflammatory vulvar
      dermatoses with significant morbidity. The course may wax and wane but disease
      often persists for decades. These autoimmune diseases have varied clinical
      presentations that extend beyond the genitalia. Management is best undertaken
      using a multidisciplinary approach and active patient involvement. The first-line
      treatment of both conditions is superpotent topical corticosteroids. Supportive
      measures and adjunct therapies can optimize patient outcomes. Patients who fail
      to improve despite correct medication use should be re-evaluated, and clinicians
      should be vigilant in detecting concomitant contact dermatitis, secondary
      infection, and malignancy. 

PMID- 25608256
TI  - Vulvodynia.
AB  - Vulvodynia is a genital pain syndrome occurring in 7% to 8% of women. Although
      common, most practitioners are uncomfortable with the diagnosis and management of
      these women's pain, and many believe this is psychologically based.
      Multifactorial in origin, ubiquitous factors include pelvic floor muscle
      abnormalities, neuropathic pain, anxiety, and primary or secondary sexual
      dysfunction. Although there are many published studies on vulvodynia, quality
      trials that evaluate therapy are lacking. However, experience suggests that most
      patients are significantly improved with pelvic floor physical therapy,
      medication for neuropathic pain, psychological support, and attention to sexual
      function. 

PMID- 25608257
TI  - Allergic contact dermatitis of the vagina and perineum: causes, incidence of, and
      differentiating factors.
AB  - Review of allergic contact dermatitis of the vagina and perineum, including
      causes, incidence of, and differentiating factors. The causes include common
      allergens found in everyday products. The true incidence of contact dermatitis of
      the vagina and perineum is unknown, however, it is a common problem facing
      clinicians. The differentiating factors include itching, erythema, and
      persistence. 

PMID- 25608268
TI  - Is anxiety associated with hot flashes in women with breast cancer?
AB  - OBJECTIVE: Women with breast cancer are at higher risk for experiencing hot
      flashes (HFs), which is attributable, in large part, to systemic cancer
      treatments and their effects on estrogen levels. However, other factors, such as
      anxiety, could also play a role. This study aimed to assess the cross-sectional
      and temporal relationships between anxiety and HFs among women treated for breast
      cancer and to clarify the direction of these relationships. METHODS: Fifty-six
      women recently treated for breast cancer were assessed prospectively using a 14
      day Hot Flashes and Anxiety Diary (HFAD). Anxiety and HFs were also assessed
      using the Hospital Anxiety and Depression Scale-anxiety subscale and the
      Menopause-Specific Quality of Life Questionnaire-vasomotor subscale. In addition,
      HFs were objectively recorded for a continuous 24-hour period using home-based
      sternal skin conductance. RESULTS: No cross-sectional relationship was found
      between anxiety and subjectively assessed HFs, or between anxiety and the
      frequency and intensity of objectively assessed HFs. However, a greater anxiety
      level on the HFAD was significantly associated with a shorter time to reach the
      HF peak, as assessed with sternal skin conductance (partial Spearman correlation
      coefficient rsp = -0.44). Moreover, greater anxiety predicted more severe self
      reported HFs on the following night, both assessed with the HFAD (rsp = 0.13).
      Conversely, self-reported diurnal and nocturnal HFs on the HFAD did not predict
      next-day anxiety level. CONCLUSIONS: This study reveals a significant
      relationship between anxiety and faster-developing objectively measured HFs.
      Furthermore, anxiety has been found to significantly predict subsequent increases
      in self-reported HFs, suggesting that strategies that target anxiety could
      potentially have a beneficial effect on HFs in women with breast cancer.

PMID- 25608269
TI  - Histological study on the effects of microablative fractional CO2 laser on
      atrophic vaginal tissue: an ex vivo study.
AB  - OBJECTIVE: Microablative fractional CO2 laser has been proven to determine tissue
      remodeling with neoformation of collagen and elastic fibers on atrophic skin. The
      aim of our study is to evaluate the effects of microablative fractional CO2 laser
      on postmenopausal women with vulvovaginal atrophy using an ex vivo model.
      METHODS: This is a prospective ex vivo cohort trial. Consecutive postmenopausal
      women with vulvovaginal atrophy managed with pelvic organ prolapse surgical
      operation were enrolled. After fascial plication, the redundant vaginal edge on
      one side was treated with CO2 laser (SmartXide2; DEKA Laser, Florence, Italy).
      Five different CO2 laser setup protocols were tested. The contralateral part of
      the vaginal wall was always used as control. Excessive vagina was trimmed and
      sent for histological evaluation to compare treated and nontreated tissues.
      Microscopic and ultrastructural aspects of the collagenic and elastic components
      of the matrix were studied, and a specific image analysis with computerized
      morphometry was performed. We also considered the fine cytological aspects of
      connective tissue proper cells, particularly fibroblasts. RESULTS: During the
      study period, five women were enrolled, and 10 vaginal specimens were finally
      retrieved. Four different settings of CO2 laser were compared. Protocols were
      tested twice each to confirm histological findings. Treatment protocols were
      compared according to histological findings, particularly in maximal depth and
      connective changes achieved. All procedures were uneventful for participants.
      CONCLUSIONS: This study shows that microablative fractional CO2 laser can produce
      a remodeling of vaginal connective tissue without causing damage to surrounding
      tissue.

PMID- 25608270
TI  - Effects of estrogen deprivation on expression of aquaporins in rat vagina.
AB  - OBJECTIVE: This study aims to investigate the expression of aquaporin (AQP) 0,
      AQP3, AQP5, AQP6, AQP10, AQP11, and AQP12 in the vaginal tissue of ovariectomized
      rats. METHODS: Eight-week-old female Sprague-Dawley rats (n = 18) were randomly
      divided into three groups: control group (n = 6), ovariectomy group (n = 6), and
      ovariectomy/estrogen therapy group (n = 6). After 4 weeks, vaginal lubrication
      level and expression of AQP0, AQP3, AQP5, AQP6, AQP10, AQP11, and AQP12 in
      vaginal tissue were examined. RESULTS: Serum estrogen level was significantly
      lower in the ovariectomy group than in the control and ovariectomy/estrogen
      therapy groups (P < 0.05). Vaginal lubrication was significantly lower in the
      ovariectomy group (mean [SD], 1.62 [0.30]) than in the control group (mean [SD],
      2.37 [0.70]) and ovariectomy/estrogen therapy group (mean [SD], 2.38 [0.73]; P <
      0.05). Protein expression of AQP0, AQP3, AQP5, AQP6, AQP10, AQP11, and AQP12 was
      significantly lower in the ovariectomy group than in the control and
      ovariectomy/estrogen therapy groups (P < 0.05). CONCLUSIONS: Decreased vaginal
      lubrication in ovariectomized rats after electrostimulation may be partly caused
      by decreased AQPs in vaginal tissue.

PMID- 25608271
TI  - Adult mesenchymal stem cells and women's health.
AB  - Adult mesenchymal stem cells (MSCs) were previously described as multipotent
      cells that could differentiate into bone, cartilage, muscle, and other
      mesenchymal tissues. New information suggests that MSCs can be found in every
      tissue of the body because they function as perivascular cells--pericytes--found
      outside all blood vessels. When these vessels break or are inflamed, pericytes
      are detached and form MSCs, which are activated by their local microenvironment
      of injury. Such MSCs function to secrete powerful immune-modulatory and
      regenerative agents; more than 450 clinical trials are now ongoing, covering a
      huge spectrum of clinical conditions. How such activated MSCs affect menstrual
      cycle, menopause, or osteotrophic cancers has only recently been studied. This
      article outlines these issues and challenges the scientific and medical community
      to use this newfound knowledge to uncover new clinical logics and medial
      solutions for women.

PMID- 25608272
TI  - Risk factors for falls in a longitudinal cohort study of Saudi postmenopausal
      women: the Center of Excellence for Osteoporosis Research Study.
AB  - OBJECTIVE: This study aims to identify possible risk factors for falls among
      Saudi postmenopausal women in a population-based study. METHODS: Seven hundred
      seven postmenopausal women aged 50 years or older were followed in a prospective
      cohort study. Participant demographic characteristics, medical history, lifestyle
      factors, past-year history of falls, and physical activity (PA) scores were
      assessed. We recorded single and multiple falls, anthropometric parameters, five
      special physical performance tests, hormone levels, and bone mineral density
      measurements. Data on knee osteoarthritis (OA), lumbar spondylosis, and
      osteopenia were collected. Knee and lower back pain were assessed by interview,
      and cognition was assessed with Mini-Mental State Examination. RESULTS: During
      the mean (SD) follow-up of 5.2 (1.3) years, 164 women (23.2%) reported at least
      one fall, of whom 73 women (10.3%) reported multiple falls. Six independent
      predictors of all falls were identified: PA score of 12.61 or lower (lowest
      quartile; odds ratio [OR], 4.10; 95% CI, 1.82-8.90); past-year history of falls
      (OR, 2.44; 95% CI, 2.30-2.90); age 65 years or older (OR, 2.16; 95% CI,1.30
      3.12); presence of knee OA (OR, 1.56; 95% CI,1.03-2.34); handgrip strength of
      13.88 kg or lower (lowest quartile; OR, 1.33; 95% CI,1.09-1.64); and 8-ft walk
      test of 3.94 s or longer (highest quartile; OR, 1.18; 95% CI, 1.07-1.35).
      CONCLUSIONS: Poor PA score, past-year history of falls, age 65 years or older,
      presence of knee OA, poor handgrip strength, and prolonged time on the 8-ft walk
      test are risk factors for all falls among Saudi postmenopausal women.

PMID- 25608273
TI  - Facilitating lifestyle changes to manage menopausal symptoms in women with breast
      cancer: a randomized controlled pilot trial of The Pink Women's Wellness Program.
AB  - OBJECTIVE: Women diagnosed as having breast cancer may experience difficulties
      with posttreatment effects such as menopausal symptoms. The aims of this pilot
      study were to (1) evaluate the impact of a multimodal lifestyle program on
      reducing menopausal symptoms in women with breast cancer and (2) examine the
      impact of the program on health-related quality of life (HRQoL) and adherence to
      lifestyle recommendations. METHODS: Overall, 55 women aged 45 to 60 years with
      one moderate to severe menopausal symptom and a history of breast cancer were
      randomized into an intervention group (n = 26) or a control group (n = 29). Women
      in the intervention group received a lifestyle intervention (The Pink Women's
      Wellness Program) that included clinical consultations and a tailored health
      education program. Measurements of menopausal symptoms (Greene Climacteric
      Scale), HRQoL (SF-12 and Functional Assessment of Cancer Therapy-Breast), and
      modifiable lifestyle factors (food intake, physical activity, smoking and alcohol
      use, and sleep disturbance) were taken at baseline and 12 weeks. RESULTS: Women
      in the intervention group reported clinically significant reductions in many
      menopausal symptoms, specifically somatic symptoms (d = 0.52), vasomotor symptoms
      (d = 0.55), sexual dysfunction (d = .65), and overall menopausal symptoms (d =
      0.54), at 12 weeks compared with the control group (d = 0.03, d = 0.24, d = 0.18,
      and d = 0.05, respectively). Women in the intervention group reported
      improvements in Functional Assessment of Cancer Therapy-Breast subscale scores,
      physical well-being and functional well-being, and Functional Assessment of
      Cancer Therapy-General total scores (intervention group: d = 0.54, d = 0.50, and
      d = 0.48, respectively; control group: d = 0.22, d = 0.11, and d = 0.05,
      respectively). CONCLUSIONS: The Pink Women's Wellness Program is effective in
      decreasing menopausal symptoms, thus improving HRQoL. This being a pilot study,
      further research is recommended to investigate the benefits of combining
      nonpharmacological interventions for women with breast cancer to reduce their
      treatment-related menopausal symptoms.

PMID- 25608274
TI  - Postoperative voiding difficulty and mesh-related complications after Total
      Prolift System surgical repair for pelvic organ prolapse and predisposing
      factors.
AB  - OBJECTIVE: We aimed to evaluate the incidence and predisposing factors of
      postoperative voiding difficulty and mesh-related complications. METHODS: In this
      prospective cohort study, 206 consecutive women with advanced pelvic organ
      prolapse underwent surgical repair with the Prolift mesh kit at Peking Union
      Medical College Hospital, with a mean follow-up of 4.2 years. Postoperative
      voiding difficulty was defined as postvoid bladder volume of 100 mL or more (or
      more than one third of voided volume). The International Urogynecological
      Association/International Continence Society joint terminology was used for mesh
      related complications and pain. Symptomatic recurrence was defined as symptomatic
      Pelvic Organ Prolapse Quantification stage II or higher. chi test and univariate
      or multivariate logistic regression were used for data analysis. RESULTS:
      Fourteen (6.8%) women were lost to follow-up. Postoperative voiding difficulty
      occurred in 60 of 192 (31.25%) women; low preoperative average urine flow (odds
      ratio [OR], 4.7; 95% CI, 1.3-17.2) and residual urine volume (OR, 2.6; 95% CI,
      1.3-5.0) were independent risk factors. In total, 85% (51 of 60) reported symptom
      resolution within 3 days. Women with a postoperative residual urine volume of 200
      mL or more experienced a more difficult recovery (P = 0.01). Mesh-related
      complications were reported in 29 of 192 (15.1%) women, with vaginal
      complications (mesh exposure/contraction) accounting for 69.0% (20 of 29).
      Greater blood loss (OR, 5.9; 95% CI, 2.1-18.7) and past pelvic surgical operation
      (OR, 6.3; 95% CI, 1.3-23.8) were strongly related to these complications. Three
      hematomas (7A) and six skin complications (6B) were also reported. However, the
      small participant sample prevented pain and recurrence analyses. CONCLUSIONS: Low
      average urine flow rate and preoperative urinary retention can be used to predict
      postoperative voiding difficulty. Vaginal complications (mesh
      exposure/contraction) are the primary mesh-related complications and are
      predicted by greater blood loss and past pelvic surgical operation.

PMID- 25608275
TI  - Effectiveness of silk fabric underwear as an adjuvant tool in the management of
      vulvar lichen simplex chronicus: results of a double-blind randomized controlled
      trial.
AB  - OBJECTIVE: Avoiding potentially irritating contact is a key point in vulvar
      lichen simplex chronicus (VLSC) management. This study aims to assess the use of
      nonirritating silk fabric underwear (Dermasilk) as an adjuvant tool in the
      treatment of VLSC. METHODS: Twenty women with VLSC were enrolled in a 1-week open
      label active treatment phase with topical 0.1% mometasone furoate (MMF) ointment.
      Participants then entered a 4-week double-blind maintenance phase (MP) in which
      they were randomized to wear either silk fabric or cotton briefs. During MP,
      participants were allowed to use MMF on an "as-needed" basis. The main efficacy
      endpoints were to assess and compare the two intervention groups on the
      following: (1) number of participants who needed to apply MMF throughout MP; (2)
      mean number of MMF applications; (3) mean symptom-free interval before MMF
      reapplication; and (4) changes in the severity of symptoms and signs. RESULTS:
      During MP, four women in the silk fabric briefs group applied MMF compared with
      six women in the cotton briefs group (relative risk, 0.66). The mean number of
      MMF applications was lower in the silk fabric briefs group than in the cotton
      briefs group (P = 0.074). VLSC symptom-free interval was 22.5 days in the silk
      fabric briefs group and 7.2 days in the cotton briefs group (P = 0.0003). At the
      end of MP, symptom improvement determined after corticosteroid use increased in
      the silk fabric briefs group but worsened in the cotton briefs group.
      CONCLUSIONS: Silk fabric underwear may be a useful tool for the management of
      VLSC by diminishing external sources of irritation and may reduce use of
      corticosteroids.

PMID- 25608276
TI  - Correlation of electron transport and photocatalysis of nanocrystalline clusters
      studied by Monte-Carlo continuity random walking.
AB  - In this research, Monte-Carlo Continuity Random Walking (MC-RW) model was used to
      study the relation between electron transport and photocatalysis of nano
      crystalline (nc) clusters. The effects of defect energy disorder, spatial
      disorder of material structure, electron density, and interfacial
      transfer/recombination on the electron transport and the photocatalysis were
      studied. Photocatalytic activity is defined as 1/tau from a statistical viewpoint
      with tau being the electron average lifetime. Based on the MC-RW simulation, a
      clear physical and chemical "picture" was given for the photocatalytic kinetic
      analysis of nc-clusters. It is shown that the increase of defect energy disorder
      and material spatial structural disorder, such as the decrease of defect trap
      number, the increase of crystallinity, the increase of particle size, and the
      increase of inter-particle connection, can enhance photocatalytic activity
      through increasing electron transport ability. The increase of electron density
      increases the electron Fermi level, which decreases the activation energy for
      electron de-trapping from traps to extending states, and correspondingly
      increases electron transport ability and photocatalytic activity. Reducing
      recombination of electrons and holes can increase electron transport through the
      increase of electron density and then increases the photocatalytic activity. In
      addition to the electron transport, the increase of probability for electrons to
      undergo photocatalysis can increase photocatalytic activity through the increase
      of the electron interfacial transfer speed. 

PMID- 25608277
TI  - Activation of a MnO2 cathode by water-stimulated Mg(2+) insertion for a magnesium
      ion battery.
AB  - Magnesium batteries have been considered to be one of the promising beyond
      lithium ion technologies due to magnesium's abundance, safety, and high
      volumetric capacity. However, very few materials show reversible performance as a
      cathode in magnesium ion systems. We present herein the best reported cycling
      performances of MnO2 as a magnesium battery cathode material. We show that the
      previously reported poor Mg(2+) insertion/deinsertion capacities in MnO2 can be
      greatly improved by synthesizing self-standing nanowires and introducing a small
      amount of water molecules into the electrolyte. Electrochemical and elemental
      analysis results revealed that the magnitude of Mg(2+) insertion into MnO2 highly
      depends on the ratio between water molecules and Mg(2+) ions present in the
      electrolyte and the highest Mg(2+) insertion capacity was observed at a ratio of
      6H2O/Mg(2+) in the electrolyte. We demonstrate for the first time, that MnO2
      nanowire electrode can be "activated" for Mg(2+) insertion/deinsertion by cycling
      in water containing electrolyte resulting in enhanced reversible Mg(2+)
      insertion/deinsertion even with the absence of water molecules. The MnO2 nanowire
      electrode cycled in dry Mg electrolyte after activation in water-containing
      electrolyte showed an initial capacity of 120 mA h g(-1) at a rate of 0.4 C and
      maintained 72% of its initial capacity after 100 cycles. 

PMID- 25608278
TI  - 3D-Printed Drug/Cell Carrier Enabling Effective Release of Cyclosporin A for
      Xenogeneic Cell-Based Therapy.
AB  - Systemic administration of the immunosuppressive drug cyclosporin A (CsA) is
      frequently associated with a number of side effects; therefore, sometimes it
      cannot be applied in sufficient dosage after allogeneic or xenogeneic cell
      transplantation. Local delivery is a possible solution to this problem. We used
      3D printing to develop a CsA-loaded 3D drug carrier for the purpose of local and
      sustained delivery of CsA. The carrier is a hybrid of CsA-poly(lactic-co-glycolic
      acid) (PLGA) microsphere-loaded hydrogel and a polymeric framework so that
      external force can be endured under physiological conditions. The expression of
      cytokines, which are secreted by spleen cells activated by Con A, and which are
      related to immune rejection, was significantly decreased in vitro by the released
      CsA from the drug carrier. Drug carriers seeded with xenogeneic cells (human lung
      fibroblast) were subcutaneously implanted into the BALB/c mouse. As a result, T
      cell-mediated rejection was also significantly suppressed for 4 weeks. These
      results show that the developed 3D drug carrier can be used as an effective
      xenogeneic cell delivery system with controllable immunosuppressive drugs for
      cell-based therapy. 

PMID- 25608279
TI  - Delivering clinical trials and observational studies in child eye health: a
      nationwide survey in the United Kingdom.
AB  - PURPOSE: Evidence-based medicine requires primary results from randomized
      controlled trials and high-quality observational studies; however, in pediatric
      medicine it can be difficult to enroll sufficient numbers of children to reach
      sample sizes required for statistical significance. The experience of clinicians
      and researchers with the practicalities of recruitment has not been explored, but
      could potentially inform best practice and lead to the development of successful
      research networks. Perceived barriers and facilitators to recruitment in child
      eye health in the United Kingdom, where adoption of trials and studies onto a
      central database has created a register of high quality projects, were
      investigated. METHODS: Studies and trials in child eye health from the United
      Kingdom Clinical Research Network portfolio database were identified and the
      named researchers contacted. Based on a validated tool, an electronic survey was
      created to ask about recruitment experience to identify facilitators and
      barriers. RESULTS: There were 46 trials and studies recruiting children, and 51
      completed questionnaires from researchers were received. Children's eye research
      activity is mainly based at tertiary referral centers. Although most studies
      recruit to target, many researchers report difficulties. Availability of
      dedicated research teams in clinics and good communication between research team,
      clinical team, and families are strong facilitators. Administrative difficulties
      and the burden of research to clinical teams and families are strong barriers.
      CONCLUSIONS: Support for investigators in the form of dedicated research and
      administrative staff and good communication enhance recruitment to studies in
      child eye health.

PMID- 25608280
TI  - Evaluation of the accuracy of grading indirect ophthalmoscopy video images for
      retinopathy of prematurity screening.
AB  - PURPOSE: To determine whether digital retinal images obtained using a video
      indirect ophthalmoscopy system can be accurately graded for zone, stage of
      retinopathy of prematurity (ROP), and plus or pre-plus disease, and used to
      screen for type 1 ROP. METHODS: Charts of 114 infants who had retinal video
      images acquired using the video indirect ophthalmoscopy system during routine ROP
      examinations were retrospectively reviewed. Two masked ophthalmologists (1 expert
      and 1 non-expert in ROP screening) graded the video images for image quality,
      zone, stage of ROP, and pre-plus or plus disease. The ophthalmologists' grades of
      the videos were compared to the clinical examination results, which served as the
      reference standard. The sensitivity and specificity of two predefined criteria
      for referral in detecting disease requiring treatment (ie, type 1 ROP) were then
      determined. RESULTS: Of images the expert considered fair or good quality (n =
      68), the expert and non-expert correctly identified zone (75% vs 74% of images,
      respectively), stage of ROP (75% vs 40% of images, respectively), and the
      presence of pre-plus or plus disease (79% of images). Expert and non-expert
      judgment of pre-threshold disease, pre-plus disease, or plus disease had 100%
      sensitivity and 75% versus 79% specificity, respectively, for detecting type 1
      ROP. Expert and non-expert judgment of pre-plus or plus disease had 92% versus
      100% sensitivity and 77% versus 82% specificity, respectively, for detecting type
      1 ROP. CONCLUSIONS: High-quality retinal video images can be read with high
      sensitivity and acceptable specificity to screen for type 1 ROP. Grading for pre
      plus or plus disease alone may be sufficient for the purpose of ROP screening.

PMID- 25608281
TI  - Cataract surgery in children with uveitis: retrospective analysis of intraocular
      lens implantation with anterior optic capture.
AB  - PURPOSE: To present experience with cataract extraction in 9 eyes of 7 pediatric
      patients with chronic uveitis and compare the technique of anterior optic capture
      in 5 eyes that underwent cataract extraction without optic capture of the
      intraocular lens (IOL) or were left aphakic. METHODS: A retrospective review of
      pediatric patients with chronic uveitis undergoing cataract surgery was
      performed, examining the preoperative and postoperative visual acuity,
      immunosuppressive therapy, surgical technique, complications, subsequent
      procedures, and need for escalation of systemic immunosuppressive therapy. The
      technique of anterior optic capture is described in detail. RESULTS: Of the 9
      eyes, 5 underwent cataract extraction with IOL placement with the haptics in the
      capsular bag and optic prolapsed through the anterior capsulorhexis. One eye
      underwent cataract extraction with IOL implantation in the bag. Three eyes had
      lensectomy without IOL placement. The eyes with anterior optic capture had no
      adverse outcomes and uveitis flares were controlled with topical medications and
      systemic immunosuppressants; the eye with IOL placement without optic capture had
      recurrent membranes and uveitis flares, necessitating increased systemic
      immunosuppression. All eyes achieved best-corrected visual acuity of 20/60 or
      better by 6 months following surgery and 20/30 or better at the most recent
      follow-up. CONCLUSIONS: The technique of cataract extraction with IOL placement
      and anterior prolapse of the optic through the anterior capsulorhexis shows
      promise to be a safe and viable option for pediatric patients with chronic
      uveitis treated with systemic immunotherapy.

PMID- 25608283
TI  - A 300-mV 220-nW event-driven ADC with real-time QRS detection for wearable ECG
      sensors.
AB  - This paper presents an ultra-low-power event-driven analog-to-digital converter
      (ADC) with real-time QRS detection for wearable electrocardiogram (ECG) sensors
      in wireless body sensor network (WBSN) applications. Two QRS detection
      algorithms, pulse-triggered (PUT) and time-assisted PUT (t-PUT), are proposed
      based on the level-crossing events generated from the ADC. The PUT detector
      achieves 97.63% sensitivity and 97.33% positive prediction in simulation on the
      MIT-BIH Arrhythmia Database. The t-PUT improves the sensitivity and positive
      prediction to 97.76% and 98.59% respectively. Fabricated in 0.13 MUm CMOS
      technology, the ADC with QRS detector consumes only 220 nW measured under 300 mV
      power supply, making it the first nanoWatt compact analog-to-information (A2I)
      converter with embedded QRS detector. 

PMID- 25608282
TI  - Reliability and application variability of a commercially available infrared
      videonystagmography unit.
AB  - PURPOSE: Nystagmus is a condition of involuntary eye movement. The causes for
      nystagmus may be congenital, idiopathic, or acquired. Considerable debate exists
      on the therapeutic potential of various surgical techniques. Currently, there are
      neither standardized protocols nor devices to record quantitative data on
      patients with clinical nystagmus undergoing various procedures at multiple
      centers to facilitate randomized prospective clinical trials. METHODS: The
      authors evaluated the reliability and variability of a commercially available
      infrared videonystagmography unit by recording eye movement waveforms elicited
      from normal volunteers (n = 117, 13 patients, 9 trials) by different examiners
      (A, B, and C). Five movement characteristics were examined, including saccadic
      latency, velocity and precision, and pursuit gain and velocity. RESULTS: The
      overall test/retest variability was low, where the median coefficient of
      variation of the three testers for all five eye movement categories was less than
      15%, and less than 10% of the coefficients of variation calculated were more than
      20%. However, there was a significant difference in interobserver variability for
      all outcomes, except saccade latency. CONCLUSIONS: The between-tester analysis
      was found to have greater variability than the test/retest reliability analysis.
      Future studies at multiple sites using videonystagmography measurements should
      aim to have each patient repeatedly tested by the same tester. In anticipation of
      multicenter, randomized, prospective clinical trials of surgical procedures for
      nystagmus, standardized protocols for nystagmographic data collection and
      analysis must be validated both within and among participating centers.

PMID- 25608284
TI  - A 1.33 MUW 8.02-ENOB 100 kS/s successive approximation ADC with supply reduction
      technique for implantable retinal prosthesis.
AB  - This paper presents a chip level 9 bits Charge Folding Successive-Approximation
      Register (SAR) Analog-to-Digital Converter (ADC) to be used in a CMOS image
      sensor for retinal prosthesis. It has a maximum single-ended input range of 1.8 V
      but only uses a supply voltage of 0.9 V for the entire ADC through the Charge
      Folding method. Therefore, the input range is no longer limited by the supply
      rail as in conventional SAR ADC. Moreover, the ADC is controlled by an internal
      delay line based Asynchronous Clock Generator which can be programmed to adjust
      the resolution of the ADC from 5 to 9 bits. Therefore, resolution adaptation
      function can be applied to improve the energy efficiency up to 15%. The test chip
      is implemented in 0.18 MUm CMOS process and occupies an area of 0.15 mm(2). At
      0.9 V and 100 kS/s, the 9 bit s ADC consumes 1.33 MUW and achieves an energy
      efficiency of 51.3 fJ/conversion-step . In addition, the power consumption can be
      further reduced by scaling the supply voltage and sampling frequency. At 100
      kS/s, this ADC is capable of converting the input signal at a rate equivalent to
      30 frames/s for a pixel array up to 3200 pixels. 

PMID- 25608285
TI  - A wireless capsule system with ASIC for monitoring the physiological signals of
      the human gastrointestinal tract.
AB  - This paper presents the design of a wireless capsule system for monitoring the
      physiological signals of the human gastrointestinal (GI) tract. The primary
      components of the system include a wireless capsule, a portable data recorder,
      and a workstation. Temperature, pH, and pressure sensors; an RF transceiver; a
      controlling and processing application specific integrated circuit (ASIC); and
      batteries were applied in a wireless capsule. Decreasing capsule size, improving
      sensor precision, and reducing power needs were the primary challenges; these
      were resolved by employing micro sensors, optimized architecture, and an ASIC
      design that include power management, clock management, a programmable gain
      amplifier (PGA), an A/D converter (ADC), and a serial peripheral interface (SPI)
      communication unit. The ASIC has been fabricated in 0.18- MUm CMOS technology
      with a die area of 5.0 mm * 5.0 mm. The wireless capsule integrating the ASIC
      controller measures Phi 11 mm * 26 mm. A data recorder and a workstation were
      developed, and 20 cases of human experiments were conducted in hospitals.
      Preprocessing in the workstation can significantly improve the quality of the
      data, and 76 original features were determined by mathematical statistics. Based
      on the 13 optimal features achieved in the evaluation of the features, the
      clustering algorithm can identify the patients who lack GI motility with a
      recognition rate reaching 83.3%. 

PMID- 25608286
TI  - Modified neural dynamic surface approach to output feedback of MIMO nonlinear
      systems.
AB  - We report an adaptive output feedback dynamic surface control (DSC), maintaining
      the prescribed performance, for a class of uncertain nonlinear systems with
      multiinput and multioutput. Designing neural network observers and modifying the
      DSC method achieves several control objectives. First, to achieve output feedback
      control, the finite-time echo state networks (ESN) observer with fast convergence
      is designed to obtain the online system states. Thus, the immeasurable states in
      traditional state feedback control are estimated and the unknown functions are
      approximated by ESN. Then, a modified DSC approach is developed by introducing a
      high-order sliding mode differentiator to replace the first-order filter in each
      step. Thus, the effect of filter performance on closed-loop stability is reduced.
      Furthermore, the input to state stability guarantees that all signals of the
      whole closed-loop system are semiglobally uniformly ultimately bounded.
      Specifically, the performance functions make the tracking errors converge to a
      compact set around equilibrium. Two numerical examples illustrated the proposed
      control scheme with satisfactory results. 

PMID- 25608287
TI  - Efficient l1 -norm-based low-rank matrix approximations for large-scale problems
      using alternating rectified gradient method.
AB  - Low-rank matrix approximation plays an important role in the area of computer
      vision and image processing. Most of the conventional low-rank matrix
      approximation methods are based on the l2 -norm (Frobenius norm) with principal
      component analysis (PCA) being the most popular among them. However, this can
      give a poor approximation for data contaminated by outliers (including missing
      data), because the l2 -norm exaggerates the negative effect of outliers.
      Recently, to overcome this problem, various methods based on the l1 -norm, such
      as robust PCA methods, have been proposed for low-rank matrix approximation.
      Despite the robustness of the methods, they require heavy computational effort
      and substantial memory for high-dimensional data, which is impractical for real
      world problems. In this paper, we propose two efficient low-rank factorization
      methods based on the l1 -norm that find proper projection and coefficient
      matrices using the alternating rectified gradient method. The proposed methods
      are applied to a number of low-rank matrix approximation problems to demonstrate
      their efficiency and robustness. The experimental results show that our proposals
      are efficient in both execution time and reconstruction performance unlike other
      state-of-the-art methods. 

PMID- 25608288
TI  - Semisupervised feature selection via spline regression for video semantic
      recognition.
AB  - To improve both the efficiency and accuracy of video semantic recognition, we can
      perform feature selection on the extracted video features to select a subset of
      features from the high-dimensional feature set for a compact and accurate video
      data representation. Provided the number of labeled videos is small, supervised
      feature selection could fail to identify the relevant features that are
      discriminative to target classes. In many applications, abundant unlabeled videos
      are easily accessible. This motivates us to develop semisupervised feature
      selection algorithms to better identify the relevant video features, which are
      discriminative to target classes by effectively exploiting the information
      underlying the huge amount of unlabeled video data. In this paper, we propose a
      framework of video semantic recognition by semisupervised feature selection via
      spline regression (S(2)FS(2)R) . Two scatter matrices are combined to capture
      both the discriminative information and the local geometry structure of labeled
      and unlabeled training videos: A within-class scatter matrix encoding
      discriminative information of labeled training videos and a spline scatter output
      from a local spline regression encoding data distribution. An l2,1 -norm is
      imposed as a regularization term on the transformation matrix to ensure it is
      sparse in rows, making it particularly suitable for feature selection. To
      efficiently solve S(2)FS(2)R , we develop an iterative algorithm and prove its
      convergency. In the experiments, three typical tasks of video semantic
      recognition, such as video concept detection, video classification, and human
      action recognition, are used to demonstrate that the proposed S(2)FS(2)R achieves
      better performance compared with the state-of-the-art methods. 

PMID- 25608289
TI  - A scalable projective scaling algorithm for l(p) loss with convex penalizations.
AB  - This paper presents an accurate, efficient, and scalable algorithm for minimizing
      a special family of convex functions, which have a lp loss function as an
      additive component. For this problem, well-known learning algorithms often have
      well-established results on accuracy and efficiency, but there exists rarely any
      report on explicit linear scalability with respect to the problem size. The
      proposed approach starts with developing a second-order learning procedure with
      iterative descent for general convex penalization functions, and then builds
      efficient algorithms for a restricted family of functions, which satisfy the
      Karmarkar's projective scaling condition. Under this condition, a light weight,
      scalable message passing algorithm (MPA) is further developed by constructing a
      series of simpler equivalent problems. The proposed MPA is intrinsically scalable
      because it only involves matrix-vector multiplication and avoids matrix inversion
      operations. The MPA is proven to be globally convergent for convex formulations;
      for nonconvex situations, it converges to a stationary point. The accuracy,
      efficiency, scalability, and applicability of the proposed method are verified
      through extensive experiments on sparse signal recovery, face image
      classification, and over-complete dictionary learning problems. 

PMID- 25608290
TI  - Scatter balance: an angle-based supervised dimensionality reduction.
AB  - Subspace selection is widely applied in data classification, clustering, and
      visualization. The samples projected into subspace can be processed efficiently.
      In this paper, we research the linear discriminant analysis (LDA) and maximum
      margin criterion (MMC) algorithms intensively and analyze the effects of scatters
      to subspace selection. Meanwhile, we point out the boundaries of scatters in LDA
      and MMC algorithms to illustrate the differences and similarities of subspace
      selection in different circumstances. Besides, the effects of outlier classes on
      subspace selection are also analyzed. According to the above analysis, we propose
      a new subspace selection method called angle linear discriminant embedding (ALDE)
      on the basis of angle measurement. ALDE utilizes the cosine of the angle to get
      new within-class and between-class scatter matrices and avoids the small sample
      size problem simultaneously. To deal with high-dimensional data, we extend ALDE
      to a two-stage ALDE (TS-ALDE). The synthetic data experiments indicate that ALDE
      can balance the within-class and between-class scatters and be robust to outlier
      classes. The experimental results based on UCI machine-learning repository and
      image databases show that TS-ALDE has a lower time complexity than ALDE while
      processing high-dimensional data. 

PMID- 25608291
TI  - Consensus in continuous-time multiagent systems under discontinuous nonlinear
      protocols.
AB  - In this paper, we provide a theoretical analysis for nonlinear discontinuous
      consensus protocols in networks of multiagents over weighted directed graphs. By
      integrating the analytic tools from nonsmooth stability analysis and graph
      theory, we investigate networks with both fixed topology and randomly switching
      topology. For networks with a fixed topology, we provide a sufficient and
      necessary condition for asymptotic consensus, and the consensus value can be
      explicitly calculated. As to networks with switching topologies, we provide a
      sufficient condition for the network to realize consensus almost surely. In
      particular, we consider the case that the switching sequence is independent and
      identically distributed. As applications of the theoretical results, we introduce
      a generalized blinking model and show that consensus can be realized almost
      surely under the proposed protocols. Numerical simulations are also provided to
      illustrate the theoretical results. 

PMID- 25608292
TI  - Backstepping fuzzy-neural-network control design for hybrid maglev transportation
      system.
AB  - This paper focuses on the design of a backstepping fuzzy-neural-network control
      (BFNNC) for the online levitated balancing and propulsive positioning of a hybrid
      magnetic levitation (maglev) transportation system. The dynamic model of the
      hybrid maglev transportation system including levitated hybrid electromagnets to
      reduce the suspension power loss and the friction force during linear movement
      and a propulsive linear induction motor based on the concepts of mechanical
      geometry and motion dynamics is first constructed. The ultimate goal is to design
      an online fuzzy neural network (FNN) control methodology to cope with the problem
      of the complicated control transformation and the chattering control effort in
      backstepping control (BSC) design, and to directly ensure the stability of the
      controlled system without the requirement of strict constraints, detailed system
      information, and auxiliary compensated controllers despite the existence of
      uncertainties. In the proposed BFNNC scheme, an FNN control is utilized to be the
      major control role by imitating the BSC strategy, and adaptation laws for network
      parameters are derived in the sense of projection algorithm and Lyapunov
      stability theorem to ensure the network convergence as well as stable control
      performance. The effectiveness of the proposed control strategy for the hybrid
      maglev transportation system is verified by experimental results, and the
      superiority of the BFNNC scheme is indicated in comparison with the BSC strategy
      and the backstepping particle-swarm-optimization control system in previous
      research. 

PMID- 25608293
TI  - Adaptive hidden Markov model with anomaly States for price manipulation
      detection.
AB  - Price manipulation refers to the activities of those traders who use carefully
      designed trading behaviors to manually push up or down the underlying equity
      prices for making profits. With increasing volumes and frequency of trading,
      price manipulation can be extremely damaging to the proper functioning and
      integrity of capital markets. The existing literature focuses on either empirical
      studies of market abuse cases or analysis of particular manipulation types based
      on certain assumptions. Effective approaches for analyzing and detecting price
      manipulation in real time are yet to be developed. This paper proposes a novel
      approach, called adaptive hidden Markov model with anomaly states (AHMMAS) for
      modeling and detecting price manipulation activities. Together with wavelet
      transformations and gradients as the feature extraction methods, the AHMMAS model
      caters to price manipulation detection and basic manipulation type recognition.
      The evaluation experiments conducted on seven stock tick data from NASDAQ and the
      London Stock Exchange and 10 simulated stock prices by stochastic differential
      equation show that the proposed AHMMAS model can effectively detect price
      manipulation patterns and outperforms the selected benchmark models. 

PMID- 25608294
TI  - Consensus-based distributed cooperative learning from closed-loop neural control
      systems.
AB  - In this paper, the neural tracking problem is addressed for a group of uncertain
      nonlinear systems where the system structures are identical but the reference
      signals are different. This paper focuses on studying the learning capability of
      neural networks (NNs) during the control process. First, we propose a novel
      control scheme called distributed cooperative learning (DCL) control scheme, by
      establishing the communication topology among adaptive laws of NN weights to
      share their learned knowledge online. It is further proved that if the
      communication topology is undirected and connected, all estimated weights of NNs
      can converge to small neighborhoods around their optimal values over a domain
      consisting of the union of all state orbits. Second, as a corollary it is shown
      that the conclusion on the deterministic learning still holds in the
      decentralized adaptive neural control scheme where, however, the estimated
      weights of NNs just converge to small neighborhoods of the optimal values along
      their own state orbits. Thus, the learned controllers obtained by DCL scheme have
      the better generalization capability than ones obtained by decentralized learning
      method. A simulation example is provided to verify the effectiveness and
      advantages of the control schemes proposed in this paper. 

PMID- 25608295
TI  - Delay-based reservoir computing: noise effects in a combined analog and digital
      implementation.
AB  - Reservoir computing is a paradigm in machine learning whose processing
      capabilities rely on the dynamical behavior of recurrent neural networks. We
      present a mixed analog and digital implementation of this concept with a
      nonlinear analog electronic circuit as a main computational unit. In our
      approach, the reservoir network can be replaced by a single nonlinear element
      with delay via time-multiplexing. We analyze the influence of noise on the
      performance of the system for two benchmark tasks: 1) a classification problem
      and 2) a chaotic time-series prediction task. Special attention is given to the
      role of quantization noise, which is studied by varying the resolution in the
      conversion interface between the analog and digital worlds. 

PMID- 25608296
TI  - Non-divergence of stochastic discrete time algorithms for PCA neural networks.
AB  - Learning algorithms play an important role in the practical application of neural
      networks based on principal component analysis, often determining the success, or
      otherwise, of these applications. These algorithms cannot be divergent, but it is
      very difficult to directly study their convergence properties, because they are
      described by stochastic discrete time (SDT) algorithms. This brief analyzes the
      original SDT algorithms directly, and derives some invariant sets that guarantee
      the nondivergence of these algorithms in a stochastic environment by selecting
      proper learning parameters. Our theoretical results are verified by a series of
      simulation examples. 

PMID- 25608297
TI  - Asymmetric mixture model with simultaneous feature selection and model detection.
AB  - A mixture model based on the symmetric Gaussian distribution that simultaneously
      treats the feature selection, and the model detection has recently received great
      attention for pattern recognition problems. However, in many applications, the
      distribution of the data has a non-Gaussian and nonsymmetric form. This brief
      presents a new asymmetric mixture model for model detection and model selection.
      In this brief, the proposed asymmetric distribution is modeled with multiple
      student's- t distributions, which are heavily tailed and more robust than
      Gaussian distributions. Our method has the flexibility to fit different shapes of
      observed data, such as non-Gaussian and nonsymmetric. Another advantage is that
      the proposed algorithm, which is based on the variational Bayesian learning, can
      simultaneously optimize over the number of the student's- t distribution that is
      used to model each asymmetric distribution, the number of components, and the
      saliency of the features. Numerical experiments on both synthetic and real-world
      datasets are conducted. The performance of the proposed model is compared with
      other mixture models, demonstrating the robustness, accuracy, and effectiveness
      of our method. 

PMID- 25608298
TI  - Computerized System for Quantitative Assessment of Atherosclerotic Plaques in the
      Femoral and Iliac Arteries Visualized by Multislice Computed Tomography.
AB  - OBJECTIVE: The investigation is aimed at the development of a semiautomatic
      method of examining the femoral and iliac arteries, and quantifying
      atherosclerotic plaques visible in the multislice computed tomography images.
      METHODS: We have utilized the advanced morphology and segmentation methods for
      processing of a series of the images. In particular, a novel sorted pixel
      intensity approach to segment the artery into the lumen/plaque regions has been
      used, and effectively combined with the Gaussian mixture modeling to increase the
      accuracy of the segmentation. RESULTS: Our numerical results are compared with
      those obtained manually by two experts. Statistics relevant to the progression of
      atherosclerosis have also been suggested. Results of the semiautomatic tracking
      of the femoral and iliac arteries and of the quantitative evaluation of
      atherosclerotic alterations therein have been shown to correspond well with the
      expert's results. CONCLUSION: The developed system is likely to be valuable tool
      for supporting the quantitative evaluation of atherosclerotic changes in
      arteries. SIGNIFICANCE: In its present form the system can be used for planning
      surgical treatment and/or predicting the course of the atherosclerotic
      alterations.

PMID- 25608299
TI  - Accuracy of Femur Angles Estimated by IMUs During Clinical Procedures Used to
      Diagnose Femoroacetabular Impingement.
AB  - We present a novel method for quantifying femoral orientation angles using a
      thigh-mounted inertial measurement unit (IMU). The IMU-derived femoral
      orientation angles reproduce gold-standard motion capture angles to within mean
      (standard deviation) differences of 0.1 (1.1) degrees on cadaveric specimens
      during clinical procedures used for the diagnosis of Femoroacetabular Impingement
      (FAI). The method, which assumes a stationary pelvis, is easy to use,
      inexpensive, and provides femur motion trajectory data in addition to range of
      motion measures. These advantages may accelerate the adoption of this technology
      to inform FAI diagnoses and assess treatment efficacy. To this end, we further
      investigate the accuracy of hip joint angles calculated using this methodology
      and assess the sensitivity of our estimates to skin motion artifact during these
      tasks. 

PMID- 25608300
TI  - A Robust and Artifact Resistant Algorithm of Ultrawideband Imaging System for
      Breast Cancer Detection.
AB  - OBJECTIVE: Ultrawideband radar imaging is regarded as one of the most promising
      alternatives for breast cancer detection. A range of algorithms reported in
      literature shows satisfactory tumor detection capabilities. However, most of
      algorithms suffer significant deterioration or even fail when the early-stage
      artifact, including incident signals and skin-fat interface reflections, cannot
      be perfectly removed from received signals. Furthermore, fibro-glandular tissue
      poses another challenge for tumor detection, due to the small dielectric contrast
      between glandular and cancerous tissues. METHODS: This paper introduces a novel
      Robust and Artifact Resistant (RAR) algorithm, in which a neighborhood pairwise
      correlation-based weighting is designed to overcome the adverse effects from both
      artifact and glandular tissues. In RAR, backscattered signals are time-shifted,
      summed, and weighted by the maximum combination of the neighboring pairwise
      correlation coefficients between shifted signals, forming the intensity of each
      point within an imaging area. RESULTS: The effectiveness was investigated using 3
      D anatomically and dielectrically accurate finite-difference-time-domain
      numerical breast models. The use of neighborhood pairwise correlation provided
      robustness against artifact and enabled the detection of multiple scatterers. RAR
      is compared with four well-known algorithms: delay-and-sum, delay-multiply-and
      sum, modified-weighted-delay-and-sum, and filtered-delay-and-sum. CONCLUSION: It
      has shown that RAR exhibits improved identification capability, robust artifact
      resistance, and high detectability over its counterparts in most scenarios
      considered, while maintaining computational efficiency. Simulated tumors in both
      homogeneous and heterogonous, from mildly to moderately dense breast phantoms,
      combining an entropy-based artifact removal algorithm, were successfully
      identified and localized. SIGNIFICANCE: These results show the strong potential
      of RAR for breast cancer screening.

PMID- 25608302
TI  - Analysis of Transcranial Magnetic Stimulation Based on the Surface Integral
      Equation Formulation.
AB  - GOAL: The aim of this paper is to provide a rigorous model and, hence, a more
      accurate description of the transcranial magnetic stimulation (TMS) induced
      fields and currents, respectively, by taking into account the inductive and
      capacitive effects, as well as the propagation effects, often being neglected
      when using quasi-static approximation. METHODS: The formulation is based on the
      surface integral equation (SIE) approach. The model of a lossy homogeneous brain
      has been derived from the equivalence theorem and using the appropriate boundary
      conditions for the electric field. The numerical solution of the SIE has been
      carried out using the method of moments. RESULTS: Numerical results for the
      induced electric field, electric current density, and the magnetic flux density
      distribution inside the human brain, presented for three typical TMS coils, are
      in a good agreement with some previous analysis as well as to the results
      obtained by analytical approach. CONCLUSION: The future work should be related to
      the development of a more detailed geometrical model of the human brain that will
      take into account complex cortical columnar structures, as well as some
      additional brain tissues. SIGNIFICANCE: To the best of authors knowledge, similar
      approach in modeling TMS has not been previously reported, albeit integral
      equation methods are seeing a revival in computational electromagnetics
      community.

PMID- 25608301
TI  - A Device for Human Ultrasonic Echolocation.
AB  - OBJECTIVE: We present a device that combines principles of ultrasonic
      echolocation and spatial hearing to provide human users with environmental cues
      that are 1) not otherwise available to the human auditory system, and 2) richer
      in object and spatial information than the more heavily processed sonar cues of
      other assistive devices. The device consists of a wearable headset with an
      ultrasonic emitter and stereo microphones with affixed artificial pinnae. The
      goal of this study is to describe the device and evaluate the utility of the
      echoic information it provides. METHODS: The echoes of ultrasonic pulses were
      recorded and time stretched to lower their frequencies into the human auditory
      range, then played back to the user. We tested performance among naive and
      experienced sighted volunteers using a set of localization experiments, in which
      the locations of echo-reflective surfaces were judged using these time-stretched
      echoes. RESULTS: Naive subjects were able to make laterality and distance
      judgments, suggesting that the echoes provide innately useful information without
      prior training. Naive subjects were generally unable to make elevation judgments
      from recorded echoes. However, trained subjects demonstrated an ability to judge
      elevation as well. CONCLUSION: This suggests that the device can be used
      effectively to examine the environment and that the human auditory system can
      rapidly adapt to these artificial echolocation cues. SIGNIFICANCE: Interpreting
      and interacting with the external world constitutes a major challenge for persons
      who are blind or visually impaired. This device has the potential to aid blind
      people in interacting with their environment.

PMID- 25608303
TI  - High-accuracy stereo matching based on adaptive ground control points.
AB  - This paper proposes a novel high-accuracy stereo matching scheme based on
      adaptive ground control points (AdaptGCP). Different from traditional fixed GCP
      based methods, we consider color dissimilarity, spatial relation, and the pixel
      matching reliability to select GCP adaptively in each local support window. To
      minimize the global energy, we propose a practical solution, named as alternating
      updating scheme of disparity and confidence map, which can effectively eliminate
      the redundant and interfering information of unreliable pixels. The disparity
      values of those unreliable pixels are reassigned with the information provided by
      local plane model, which is fitted with GCPs. Then, the confidence map is updated
      according to the disparity reassignment and the left-right consistency. Finally,
      the disparity map is refined by multistep filers. Quantitative evaluations
      demonstrate the effectiveness of our AdaptGCP scheme for regularizing the ill
      posed matching problem. The top ranks on Middlebury benchmark with different
      error thresholds show that our algorithm achieves the state-of-the-art
      performance among the latest stereo matching algorithms. This paper provides a
      new insight toward high-accuracy stereo matching. 

PMID- 25608304
TI  - Saliency-based color accessibility.
AB  - Perception of color varies markedly between individuals because of differential
      expression of photopigments in retinal cones. However, it has been difficult to
      quantify the individual cognitive variation in colored scene and to predict its
      complex impacts on the behaviors. We developed a method for quantifying and
      visualizing information loss and gain resulting from individual differences in
      spectral sensitivity based on visual salience. We first modeled the visual
      salience for color-deficient observers, and found that the predicted losses and
      gains in local image salience derived from normal and color-blind models were
      correlated with the subjective judgment of image saliency in psychophysical
      experiments, i.e., saliency loss predicted reduced image preference in color
      deficient observers. Moreover,saliency-guided image manipulations sufficiently
      compensated for individual differences in saliency. This visual saliency approach
      allows for quantification of information extracted from complex visual scenes and
      can be used as an image compensation to enhance visual accessibility by color
      deficient individuals.

PMID- 25608305
TI  - Hyperspectral face recognition with spatiospectral information fusion and PLS
      regression.
AB  - Hyperspectral imaging offers new opportunities for face recognition via improved
      discrimination along the spectral dimension. However, it poses new challenges,
      including low signal-to-noise ratio, interband misalignment, and high data
      dimensionality. Due to these challenges, the literature on hyperspectral face
      recognition is not only sparse but is limited to ad hoc dimensionality reduction
      techniques and lacks comprehensive evaluation. We propose a hyperspectral face
      recognition algorithm using a spatiospectral covariance for band fusion and
      partial least square regression for classification. Moreover, we extend 13
      existing face recognition techniques, for the first time, to perform
      hyperspectral face recognition.We formulate hyperspectral face recognition as an
      image-set classification problem and evaluate the performance of seven state-of
      the-art image-set classification techniques. We also test six state-of-the-art
      grayscale and RGB (color) face recognition algorithms after applying fusion
      techniques on hyperspectral images. Comparison with the 13 extended and five
      existing hyperspectral face recognition techniques on three standard data sets
      show that the proposed algorithm outperforms all by a significant margin.
      Finally, we perform band selection experiments to find the most discriminative
      bands in the visible and near infrared response spectrum.

PMID- 25608306
TI  - Reflection symmetry detection using locally affine invariant edge correspondence.
AB  - Reflection symmetry detection receives increasing attentions in recent years. The
      state-of-the-art algorithms mainly use the matching of intensity-based features
      (such as the SIFT) within a single image to find symmetry axes. This paper
      proposes a novel approach by establishing the correspondence of locally affine
      invariant edge-based features, which are superior to the intensity based in the
      aspects that it is insensitive to illumination variations, and applicable to
      textureless objects. The locally affine invariance is achieved by simple linear
      algebra for efficient and robust computations, making the algorithm suitable for
      detections under object distortions like perspective projection. Commonly used
      edge detectors and a voting process are, respectively, used before and after the
      edge description and matching steps to form a complete reflection detection
      pipeline. Experiments are performed using synthetic and real-world images with
      both multiple and single reflection symmetry axis. The test results are compared
      with existing algorithms to validate the proposed method. 

PMID- 25608307
TI  - A Miniature, Fiber-Coupled, Wireless, Deep-Brain Optogenetic Stimulator.
AB  - Controlled, wireless neuromodulation using miniature implantable devices is a
      long-sought goal in neuroscience. It will allow many studies and treatments that
      are otherwise impractical. Recent studies demonstrate advances in neuromodulation
      through optogenetics, but test animals are typically tethered, severely limiting
      experimental possibilities. Existing nontethered optical stimulators either
      deliver light through a cranial window limiting applications to superficial
      layers of the brain, are not widely accessible due to highly specialized
      fabrication techniques, or do not demonstrate robust and flexible control of the
      optical power emitted. To overcome these limitations, we have developed a novel,
      miniature, wireless, deep-brain, modular optical stimulator with controllable
      stimulation parameters for use in optogenetic experiments. We demonstrate its use
      in a behavioral experiment targeting a deep brain structure in freely behaving
      mice. To allow its rapid and widespread adoption, we developed this stimulator
      using commercially available components. The modular and accessible optogenetic
      stimulator presented advances the wireless toolset available for freely behaving
      animal experiments. 

PMID- 25608308
TI  - Bluetooth Communication Interface for EEG Signal Recording in Hyperbaric
      Chambers.
AB  - Recording biological signals inside a hyperbaric chamber poses technical
      challenges (the steel walls enclosing it greatly attenuate or completely block
      the signals as in a Faraday cage), practical (lengthy cables creating eddy
      currents), and safety (sparks hazard from power supply to the electronic
      apparatus inside the chamber) which can be overcome with new wireless
      technologies. In this technical report we present the design and implementation
      of a Bluetooth system for electroencephalographic (EEG) recording inside a
      hyperbaric chamber and describe the feasibility of EEG signal transmission
      outside the chamber. Differently from older systems, this technology allows the
      online recording of amplified signals, without interference from eddy currents.
      In an application of this technology, we measured EEG activity in professional
      divers under three experimental conditions in a hyperbaric chamber to determine
      how oxygen, assumed at a constant hyperbaric pressure of 2.8 ATA , affects the
      bioelectrical activity. The EEG spectral power estimated by fast Fourier
      transform and the cortical sources of the EEG rhythms estimated by low-resolution
      brain electromagnetic analysis were analyzed in three different EEG acquisitions:
      breathing air at sea level; breathing oxygen at a simulated depth of 18 msw, and
      breathing air at sea level after decompression. 

PMID- 25608309
TI  - Generating conformational transitions using the euclidean distance matrix.
AB  - Elastic network interpolation (ENI) is an efficient method for generating
      intermediate conformations between two end protein conformations. Its current
      formulation uses interatomic distance. We show how this can be generalized to
      interatomic distances-squared. This generalization is part of an effort to study
      protein dynamics on the set of positive semidefinite (PSD) matrices, which has a
      rich mathematical structure. We use lattice structures to test this interpolation
      scheme, and discuss some limitations observed. We conclude with some suggestions
      for future research. 

PMID- 25608310
TI  - Deformed graph laplacian for semisupervised learning.
AB  - Graph Laplacian has been widely exploited in traditional graph-based
      semisupervised learning (SSL) algorithms to regulate the labels of examples that
      vary smoothly on the graph. Although it achieves a promising performance in both
      transductive and inductive learning, it is not effective for handling ambiguous
      examples (shown in Fig. 1). This paper introduces deformed graph Laplacian (DGL)
      and presents label prediction via DGL (LPDGL) for SSL. The local smoothness term
      used in LPDGL, which regularizes examples and their neighbors locally, is able to
      improve classification accuracy by properly dealing with ambiguous examples.
      Theoretical studies reveal that LPDGL obtains the globally optimal decision
      function, and the free parameters are easy to tune. The generalization bound is
      derived based on the robustness analysis. Experiments on a variety of real-world
      data sets demonstrate that LPDGL achieves top-level performance on both
      transductive and inductive settings by comparing it with popular SSL algorithms,
      such as harmonic functions, AnchorGraph regularization, linear neighborhood
      propagation, Laplacian regularized least square, and Laplacian support vector
      machine. 

PMID- 25608311
TI  - Data imputation through the identification of local anomalies.
AB  - We introduce a comprehensive and statistical framework in a model free setting
      for a complete treatment of localized data corruptions due to severe noise
      sources, e.g., an occluder in the case of a visual recording. Within this
      framework, we propose: 1) a novel algorithm to efficiently separate, i.e., detect
      and localize, possible corruptions from a given suspicious data instance and 2) a
      maximum a posteriori estimator to impute the corrupted data. As a generalization
      to Euclidean distance, we also propose a novel distance measure, which is based
      on the ranked deviations among the data attributes and empirically shown to be
      superior in separating the corruptions. Our algorithm first splits the suspicious
      instance into parts through a binary partitioning tree in the space of data
      attributes and iteratively tests those parts to detect local anomalies using the
      nominal statistics extracted from an uncorrupted (clean) reference data set. Once
      each part is labeled as anomalous versus normal, the corresponding binary
      patterns over this tree that characterize corruptions are identified and the
      affected attributes are imputed. Under a certain conditional independency
      structure assumed for the binary patterns, we analytically show that the false
      alarm rate of the introduced algorithm in detecting the corruptions is
      independent of the data and can be directly set without any parameter tuning. The
      proposed framework is tested over several well-known machine learning data sets
      with synthetically generated corruptions and experimentally shown to produce
      remarkable improvements in terms of classification purposes with strong
      corruption separation capabilities. Our experiments also indicate that the
      proposed algorithms outperform the typical approaches and are robust to varying
      training phase conditions. 

PMID- 25608312
TI  - L1 -norm low-rank matrix factorization by variational Bayesian method.
AB  - The L1 -norm low-rank matrix factorization (LRMF) has been attracting much
      attention due to its wide applications to computer vision and pattern
      recognition. In this paper, we construct a new hierarchical Bayesian generative
      model for the L1 -norm LRMF problem and design a mean-field variational method to
      automatically infer all the parameters involved in the model by closed-form
      equations. The variational Bayesian inference in the proposed method can be
      understood as solving a weighted LRMF problem with different weights on matrix
      elements based on their significance and with L2 -regularization penalties on
      parameters. Throughout the inference process of our method, the weights imposed
      on the matrix elements can be adaptively fitted so that the adverse influence of
      noises and outliers embedded in data can be largely suppressed, and the
      parameters can be appropriately regularized so that the generalization capability
      of the problem can be statistically guaranteed. The robustness and the efficiency
      of the proposed method are substantiated by a series of synthetic and real data
      experiments, as compared with the state-of-the-art L1 -norm LRMF methods.
      Especially, attributed to the intrinsic generalization capability of the Bayesian
      methodology, our method can always predict better on the unobserved ground truth
      data than existing methods. 

PMID- 25608313
TI  - Stability criteria for recurrent neural networks with time-varying delay based on
      secondary delay partitioning method.
AB  - A secondary delay partitioning method is proposed to study the stability problem
      for a class of recurrent neural networks (RNNs) with time-varying delay. The
      total interval of the time-varying delay is first divided into two parts, and
      then each part is further divided into several subintervals. To deal with the
      state variables associated with these subintervals, an extended reciprocal convex
      combination approach and a double integral term with variable upper and lower
      limits of integral as a Lyapunov functional are proposed, which help to obtain
      the stability criterion. The main feature of the proposed result is more
      effective for the RNNs with fast time-varying delay. A numerical example is used
      to show the effectiveness of the proposed stability result. 

PMID- 25608314
TI  - Deep and shallow architecture of multilayer neural networks.
AB  - This paper focuses on the deep and shallow architecture of multilayer neural
      networks (MNNs). The demonstration of whether or not an MNN can be replaced by
      another MNN with fewer layers is equivalent to studying the topological conjugacy
      of its hidden layers. This paper provides a systematic methodology to indicate
      when two hidden spaces are topologically conjugated. Furthermore, some criteria
      are presented for some specific cases. 

PMID- 25608315
TI  - Nonlinear model predictive control based on collective neurodynamic optimization.
AB  - In general, nonlinear model predictive control (NMPC) entails solving a
      sequential global optimization problem with a nonconvex cost function or
      constraints. This paper presents a novel collective neurodynamic optimization
      approach to NMPC without linearization. Utilizing a group of recurrent neural
      networks (RNNs), the proposed collective neurodynamic optimization approach
      searches for optimal solutions to global optimization problems by emulating
      brainstorming. Each RNN is guaranteed to converge to a candidate solution by
      performing constrained local search. By exchanging information and iteratively
      improving the starting and restarting points of each RNN using the information of
      local and global best known solutions in a framework of particle swarm
      optimization, the group of RNNs is able to reach global optimal solutions to
      global optimization problems. The essence of the proposed collective neurodynamic
      optimization approach lies in the integration of capabilities of global search
      and precise local search. The simulation results of many cases are discussed to
      substantiate the effectiveness and the characteristics of the proposed approach. 

PMID- 25608316
TI  - Noise Level Estimation for Model Selection in Kernel PCA Denoising.
AB  - One of the main challenges in unsupervised learning is to find suitable values
      for the model parameters. In kernel principal component analysis (kPCA), for
      example, these are the number of components, the kernel, and its parameters. This
      paper presents a model selection criterion based on distance distributions
      (MDDs). This criterion can be used to find the number of components and the
      sigma(2) parameter of radial basis function kernels by means of spectral
      comparison between information and noise. The noise content is estimated from the
      statistical moments of the distribution of distances in the original dataset.
      This allows for a type of randomization of the dataset, without actually having
      to permute the data points or generate artificial datasets. After comparing the
      eigenvalues computed from the estimated noise with the ones from the input
      dataset, information is retained and maximized by a set of model parameters. In
      addition to the model selection criterion, this paper proposes a modification to
      the fixed-size method and uses the incomplete Cholesky factorization, both of
      which are used to solve kPCA in large-scale applications. These two approaches,
      together with the model selection MDD, were tested in toy examples and real life
      applications, and it is shown that they outperform other known algorithms. 

PMID- 25608317
TI  - An Optimal Pulse System Design by Multichannel Sensors Fusion.
AB  - Pulse diagnosis, recognized as an important branch of traditional Chinese
      medicine (TCM), has a long history for health diagnosis. Certain features in the
      pulse are known to be related with the physiological status, which have been
      identified as biomarkers. In recent years, an electronic equipment is designed to
      obtain the valuable information inside pulse. Single-point pulse acquisition
      platform has the benefit of low cost and flexibility, but is time consuming in
      operation and not standardized in pulse location. The pulse system with a single
      type sensor is easy to implement, but is limited in extracting sufficient pulse
      information. This paper proposes a novel system with optimal design that is
      special for pulse diagnosis. We combine a pressure sensor with a photoelectric
      sensor array to make a multichannel sensor fusion structure. Then, the optimal
      pulse signal processing methods and sensor fusion strategy are introduced for the
      feature extraction. Finally, the developed optimal pulse system and methods are
      tested on pulse database acquired from the healthy subjects and the patients
      known to be afflicted with diabetes. The experimental results indicate that the
      classification accuracy is increased significantly under the optimal design and
      also demonstrate that the developed pulse system with multichannel sensors fusion
      is more effective than the previous pulse acquisition platforms. 

PMID- 25608319
TI  - Fuzzy Stochastic Optimal Guaranteed Cost Control of Bio-Economic Singular
      Markovian Jump Systems.
AB  - This paper establishes a bio-economic singular Markovian jump model by
      considering the price of the commodity as a Markov chain. The controller is
      designed for this system such that its biomass achieves the specified range with
      the least cost in a finite-time. Firstly, this system is described by Takagi
      Sugeno fuzzy model. Secondly, a new design method of fuzzy state-feedback
      controllers is presented to ensure not only the regularity, nonimpulse, and
      stochastic singular finite-time boundedness of this kind of systems, but also an
      upper bound achieved for the cost function in the form of strict linear matrix
      inequalities. Finally, two examples including a practical example of eel seedling
      breeding are given to illustrate the merit and usability of the approach proposed
      in this paper. 

PMID- 25608318
TI  - Efficient Execution Methods of Pivoting for Bulk Extraction of Entity-Attribute
      Value-Modeled Data.
AB  - Entity-attribute-value (EAV) tables are widely used to store data in electronic
      medical records and clinical study data management systems. Before they can be
      used by various analytical (e.g., data mining and machine learning) programs, EAV
      modeled data usually must be transformed into conventional relational table
      format through pivot operations. This time-consuming and resource-intensive
      process is often performed repeatedly on a regular basis, e.g., to provide a
      daily refresh of the content in a clinical data warehouse. Thus, it would be
      beneficial to make pivot operations as efficient as possible. In this paper, we
      present three techniques for improving the efficiency of pivot operations: 1)
      filtering out EAV tuples related to unneeded clinical parameters early on; 2)
      supporting pivoting across multiple EAV tables; and 3) conducting multi-query
      optimization. We demonstrate the effectiveness of our techniques through
      implementation. We show that our optimized execution method of pivoting using
      these techniques significantly outperforms the current basic execution method of
      pivoting. Our techniques can be used to build a data extraction tool to simplify
      the specification of and improve the efficiency of extracting data from the EAV
      tables in electronic medical records and clinical study data management systems. 

PMID- 25608320
TI  - [My technique: resection of the upper left section (S 1+2 and S 3)].

PMID- 25608321
TI  - [Covering using an intercostal muscle flap].

PMID- 25608322
TI  - [Q & A. Imaging diagnosis. Diaphragmatic hernia].

PMID- 25608323
TI  - [An independent specialty in nursing].

PMID- 25608324
TI  - [Communication problems are widespread on nursing wards. More than one fourth of
      nurses find patient handovers as inefficient and unstructured].

PMID- 25608325
TI  - [German underestimated nursing costs].

PMID- 25608326
TI  - [An administrative lawyer has taken a closer look at the nursing chamber. He
      points out real opportunities, but also identifies risks. Neither a panacea nor a
      placebo].

PMID- 25608327
TI  - [The Pediatric Nursing Associations of Europe have created a position paper for
      the education of nurses. Advancing pediatric nursing].

PMID- 25608328
TI  - [Until recently the dominant philosophy was to keep the truth from terminally ill
      children. This is fundamentally wrong. A plea. Speaking is gold].

PMID- 25608329
TI  - [Palliative care in the pediatric and youth hospice. Living and laughing - dying
      and grieving].

PMID- 25608330
TI  - [The family health nurse concept. Nursing care at the center of society].

PMID- 25608331
TI  - [Pediatric home nursing reduces length of stay in the hospital].

PMID- 25608332
TI  - [In the spotlight: noninvasive ventilation in neonatology from the nursing
      viewpoint. The loud lifesaver].

PMID- 25608333
TI  - [Interventions for the management of fecal incontinence in children].

PMID- 25608334
TI  - [Since more than 10 years the student congress has taken place in the Baden
      Wurttemberg Esslingen. It introduces nursing students to congresses. Learning
      about the entire spectrum of the format].

PMID- 25608335
TI  - [New nursing responsibility fields. What communities for the elderly can do].

PMID- 25608336
TI  - [Fiona Smith, coordinator of the PNAE Network has written an article about
      pediatric nursing education. We have translated it to Germany. The real test].

PMID- 25608337
TI  - [Decisions at the end of life of children and adolescents pose particular legal
      problems. Our expert illuminates the legal status. Judges can deny custody in
      certain cases].

PMID- 25608338
TI  - [The revised nursing law - impacts on the nursing structure in ambulatory nursing
      care. Private nursing service survival is threatened].

PMID- 25608339
TI  - [Qualification for ambulatory care nursing: graduate education in community
      nursing. 800 hours of theory and general practice].

PMID- 25608340
TI  - [Nursing chronically ill children. Including children and parents].

PMID- 25608341
TI  - [The maternity stay, an important step].

PMID- 25608343
TI  - [The course to follow for suspicion of Ebola].

PMID- 25608344
TI  - [An historic mobilization of professionals].

PMID- 25608342
TI  - [The concept of advanced practice should not be confused with those of expertise
      or specialization].

PMID- 25608345
TI  - [A future institute for the prevention, monitoring and public health
      administration].

PMID- 25608346
TI  - [Modifications to the evaluation of nursing students].

PMID- 25608347
TI  - [New pricing for infusions].

PMID- 25608348
TI  - [Nurses and the night shift].

PMID- 25608349
TI  - [The cost of Prado is on the hot seat].

PMID- 25608350
TI  - [Birthing center restrictions].

PMID- 25608351
TI  - [Health certificates in the first months of life].

PMID- 25608352
TI  - [Medication advice by the Ministry of Health].

PMID- 25608353
TI  - [Understanding perinatal mourning].

PMID- 25608354
TI  - [Healthcare law, proposals of the Ministry of Health].

PMID- 25608355
TI  - [Patient education sheets on preoperative instructions].

PMID- 25608356
TI  - [Adolescents, the great difficulty].

PMID- 25608357
TI  - [Cribs, always inadequate].

PMID- 25608358
TI  - [A smoking cessation program].

PMID- 25608359
TI  - [Prevalence and duration of breast feeding in France].

PMID- 25608360
TI  - [The second Walk of Light against cancer].

PMID- 25608361
TI  - [A guide for taking action against abuse].

PMID- 25608362
TI  - [Winter infections. An anticipated influx of patients].

PMID- 25608363
TI  - [Infectious disease epidemics in pediatrics].
AB  - In winter, the main infectious diseases causing epidemics in young children are
      bronchiolitis, influenza and gastroenteritis. Knowledge of the symptomatology and
      the ways in which these diseases are spread is essential for the effective care
      of the child and their family. The implementation of hygiene rules helps to limit
      the spread.

PMID- 25608364
TI  - [Overcoming the surge of patients in pediatric emergency departments in Winter].
AB  - The regular exceeding of the capacities of paediatric emergency departments in
      periods of epidemics disrupts the organisation of the management of seriously ill
      children and compromises the quality of the reception given to these children and
      their families. This recurring phenomenon raises the need for an analysis of the
      determining factors in order to find ways to improve the system and anticipate
      this period of the year which constitutes a real challenge for nursing teams.

PMID- 25608365
TI  - [The role of the triage nurse in the pediatric emergency departments].
AB  - To optimise the care of children and reduce waiting times in paediatric emergency
      departments, various human or material resources are used. The triage nurse is
      the key player at the heart of this patient management, notably in the winter
      period when the influx of patients is higher.

PMID- 25608366
TI  - [Hand hygiene and the prevention of infectious diseases in pediatrics].
AB  - To prevent infections in paediatrics certain hygiene rules must be respected.
      Hand washing constitutes the most important measure. The aim is to limit as much
      as possible the risk of spreading of hand-borne infections, in particular during
      an epidemic.

PMID- 25608367
TI  - [The immunization schedule].
AB  - Vaccination offers individual and collective protection against a number of
      infectious diseases. The immunisation schedule is updated every year and
      published by the French Ministry for Health. In 2013, the schedule was simplified
      in order to improve the vaccination coverage of the French population. Specific
      recommendations are made for health professionals.

PMID- 25608368
TI  - [Bibliography. Winter infections].

PMID- 25608369
TI  - [Chronic pain in children].
AB  - Chronic pain affects 10 to 20% of children and teenagers. Apart from the physical
      consequences, it leads to psychological and social difficulties. These notions,
      still not well known, are often overlooked. It is essential to raise the
      awareness of professionals in order to identify these young patients as early as
      possible and offer them adapted multimodal treatment. The main aim is to develop
      their autonomy to enable them to gain better understanding of this pain and to
      treat the cause when it can be identified.

PMID- 25608370
TI  - [Palliative care in pediatrics, ethics and relations with the patient].
AB  - The extension of the Belgian law on euthanasia to minors during the course of
      2014 raises questions with regard to the needs of children in the context of
      paediatric palliative care. These needs concern essentially the focus given to
      the interrelations between the child, their family and the caregiving team as
      well as to the relief of the physical, psychological and spiritual pain. Ethical
      guidelines help to fuel the discussions surrounding professional practices.

PMID- 25608371
TI  - A marriage bar of convenience? The BBC and married women's work 1923-39.
AB  - In October 1932 the British Broadcasting Corporation introduced a marriage bar,
      stemming what had been an enlightened attitude towards married women employees.
      The policy was in line with the convention of the day; marriage bars were
      widespread in the inter-war years operating in occupations such as teaching and
      the civil service and in large companies such as Sainsbury's and ICI. However,
      once implemented, the BBC displayed an ambivalent attitude towards its marriage
      bar which had been constructed to allow those married women considered useful to
      the Corporation to remain on the staff. This article considers why, for its first
      ten years, the BBC bucked convention and openly employed married women and why,
      in 1932, it took the decision to introduce a marriage bar, albeit not a full bar,
      which was not abolished until 1944. It contends that the BBC marriage bar
      represented a quest for conformity rather than active hostility towards the
      employment of married women and demonstrates how easily arguments against the
      acceptability of married women's work could be transgressed, if seen as
      beneficial to the employer. Overall, the article contemplates how far the BBC's
      marriage bar reflected inter-war ideology towards the employment of married
      women.

PMID- 25608372
TI  - The Kosmo Club case: clandestine prostitution during the interwar period.
AB  - During November 1933 the trial of three men accused of 'living off the earnings
      of prostitution' captivated the news reading public of Edinburgh. This article
      uses the detailed trial transcription and newspaper coverage of the Kosmo Club
      trial to examine the role that dance clubs played within a larger network of
      clandestine prostitution and the implications this had for the women who worked
      in these clubs as 'dance partners'. The case study focuses on a key moment in the
      history of prostitution, one that has not yet received sufficient historical
      attention, a moment when new technologies, such as the telephone and the
      motorcar, first began to dramatically alter the landscape of prostitution.
      Furthermore, the trial offers a rare glimpse of dance partners' experiences, both
      the dangers they faced and the many ways in which they attempted to resist those
      who sought to control and exploit them.

PMID- 25608373
TI  - [Tumor in the kidney. But what is causing this pain? Polymyalgia rheumatica,
      incidental renal cell carcinoma].

PMID- 25608374
TI  - [Proper use is decisive. Does "Ebola protective clothing" provide adequate
      protection?].

PMID- 25608375
TI  - [The pills are also effective in the dog].

PMID- 25608376
TI  - [Who examines the feverish patient from Africa?].

PMID- 25608377
TI  - [Risk diagnosis. Look in the crystal ball of the biomarkers].

PMID- 25608378
TI  - [Consultation according to number 03230 can be billed more often starting in
      January].

PMID- 25608379
TI  - [The treasury keeps an eye on the Christmas party].

PMID- 25608380
TI  - [KBV discriminates against general practice centered care in employment of non
      physician assistants].

PMID- 25608381
TI  - [Costs for acupuncture needles can be claimed in many cases].

PMID- 25608382
TI  - [Chamber of nursing. Self government also means self responsibility].

PMID- 25608383
TI  - [MFA magazine "info practice team". More influence and advantage in the
      professional physician network].

PMID- 25608384
TI  - [Reha-Robot makes paralized patients mobile. "Simply standing up and walking"!].

PMID- 25608385
TI  - [IMPROVE-IT Study proves effectiveness of ezetimib. The Higgs particle of
      lipidologists].

PMID- 25608386
TI  - [The GARFIELD Registry. Women with atrial fibrillation have a lower mortality
      rate].

PMID- 25608387
TI  - [Which patient will now actually benefit from ezetimib?].

PMID- 25608388
TI  - [Fewer strokes, lower mortality. Large general practice studies confirm good
      safety profile of dabigatran].

PMID- 25608389
TI  - [Myocardial infarct and normal oxygen value. Better no routine oxygen
      administration?].

PMID- 25608390
TI  - [Statistics from England. Endocarditis incidence increased after guideline
      change].

PMID- 25608391
TI  - [STIKO recommendations. Should I vaccinate all patients against influenza].

PMID- 25608392
TI  - [Bed bug alarm in Berlin. "The ignorance of people contributes to the spread"].

PMID- 25608393
TI  - [Acute respiratory tract infection. The antibiotic can wait].

PMID- 25608394
TI  - [Control of cough after common cold. Antitussive agents, steroids and coffee with
      honey].

PMID- 25608395
TI  - [Therapy of alcohol dependence. "Drying out has no effect"].

PMID- 25608396
TI  - [Naturopathy consultation. Phytotherapy medications for seniors].

PMID- 25608397
TI  - [The Care-for-Rare Center at the Dr. von Haunerschen Pediatric Hospital in
      Munich. Help for children with rare illnesses].

PMID- 25608398
TI  - [It can almost be done over the telephone. Key questions for vertigo diagnosis].

PMID- 25608399
TI  - [Nonspecific abdominal symptoms. What is going on in the intestine?].

PMID- 25608400
TI  - [Medical care overuse. Billions for mammography screening].

PMID- 25608401
TI  - [Sugar - fat tax. Why should I pay for gluttons?].

PMID- 25608402
TI  - [Lowering blood pressure without affecting risk of falling].

PMID- 25608403
TI  - [Unbelievable: highly acclaimed milk brings misfortune!].

PMID- 25608404
TI  - [Narrowly missing internal exsanguination].

PMID- 25608405
TI  - [Pramipexole for restless legs syndrome promising].

PMID- 25608406
TI  - [Sufficient sleep protects against ulcerative colitis].

PMID- 25608407
TI  - [Who would think of the thyroid gland?].

PMID- 25608408
TI  - [Foam roller exercises relieve sore muscles].

PMID- 25608409
TI  - [ Not a myocardial infarct, no lung embolism].

PMID- 25608410
TI  - [Type 1 diabetes often waits until adulthood].

PMID- 25608411
TI  - [Epistaxis is not always from the Kieselbachii locus].

PMID- 25608412
TI  - [When Ebola fever is suspected--fundamentals, preparation and management].

PMID- 25608413
TI  - ['Men are not dying with, but from prostate cancer'].

PMID- 25608414
TI  - [Diagnosis of prostate cancer].

PMID- 25608415
TI  - [Modern therapy of prostate cancer].

PMID- 25608416
TI  - [What is the reason for the formication?].

PMID- 25608417
TI  - [Abdominal pain in the elderly--what is different?].

PMID- 25608418
TI  - [Role of cardiovascular risk factors in the etiology of dementia].

PMID- 25608419
TI  - [A clear view in colonoscopy. Effective bowel cleansing: essential for successful
      colorectal cancer screening].

PMID- 25608420
TI  - [Chronic hepatitis C. Interferon free therapy also in patients with liver
      cirrhosis].

PMID- 25608421
TI  - [Improving insulin therapy in type 2 diabetes. Conquering barriers and assuring
      quality of life].

PMID- 25608422
TI  - [Dyslipidemia. Red rice supplements change in nutrition].

PMID- 25608423
TI  - [HIV management. Current challenges in HIV diagnosis and treatment].

PMID- 25608424
TI  - Measurement literature reveals numerous scientific advances in the evaluation of
      instrument reliability.

PMID- 25608425
TI  - Development and revision of the Wittmann-Price Emancipated Decision-Making Scale.
AB  - BACKGROUND AND PURPOSE: The original Emancipated Decision-Making (EDM) scale was
      revised to test 3 subconcepts (flexible environment, personal knowledge, and
      awareness of social norms) of an emancipated decision-making process. METHODS:
      The original EDM scale was significantly related to the Satisfaction with
      Decision (SWD) scale in two separate studies (r = 0.79, r = 0.59). Two of the
      original 5 subconcepts showed a lack of contribution. The third study (N = 50)
      had good total scale reliability (r = 0.89). RESULTS: The revised EDM (EDM-r)
      scale was then leveled to the SWD scores and quantified into 2 categories and the
      subscales for the 3 subconcepts were reanalyzed for reliability and scale-if-item
      contribution. CONCLUSION: The final EDM-r is a generically worded, 20-item, 3
      subscale instrument with good total and individual subscale reliability.

PMID- 25608426
TI  - The validation of the Coping and Adaptation Processing Scale based on the Roy
      adaptation model.
AB  - BACKGROUND AND PURPOSE: To establish the psychometric soundness for Coping and
      Adaptation Processing Scale (CAPS) using the Roy adaptation model as theoretical
      framework. METHOD: A descriptive, cross-sectional survey of a convenience sample
      of 199 nurses working in different acute health care facilities in California.
      The internal consistency of the multifactor CAPS questionnaire was explored using
      Cronbach's alpha coefficient. Factors correlation was examined using Pearson
      product moment correlation. The factor structure was studied using confirmatory
      factor analyses. RESULTS: In the confirmatory factor analysis, the indices of
      fitness highly supported these results. The Cronbach's alpha coefficient for the
      total score was .81 and varied between .31 and .78 in the 5 domains. A positive
      and significant correlation emerged between CAPS factors and total scores (r =
      .91, p < .01) ranging from .17 to .81. CAPS showed acceptable validity and
      reliability for measuring the coping of nurses in acute setting. Future studies
      using the scale might lead to the improvement of the subscales measurement.
      CONCLUSION: The psychometric data suggests that CAPS is a highly suitable
      instrument to measure coping processes.

PMID- 25608427
TI  - Use of the Rasch model for initial testing of fit statistics and rating scale
      diagnosis for a general anesthesia satisfaction questionnaire.
AB  - BACKGROUND AND PURPOSE: The level of patient satisfaction is a result of a
      complex set of interactions between the patient and the health care provider. It
      is important to quantify satisfaction with care because it involves the patient
      in the care experience and decreases the potential gap between expected and
      actual care delivered. METHODS: We tested a preliminary 23-item instrument to
      measure patient satisfaction with general anesthesia care. The rating scale Rasch
      model was chosen as the framework. RESULTS: There were 10 items found to have
      sufficient evidence of stable fit statistics. Items included 2 questions related
      to information provided, 2 questions related to concern and kindness of the
      provider, and 1 question each for interpersonal skills of the provider, attention
      by the provider, feeling safe, well-being, privacy, and overall anesthesia
      satisfaction. CONCLUSION: Such actions as providing enough time to understand the
      anesthesia plan, answering questions related to the anesthetic, showing kindness
      and concern for the patient, displaying good interpersonal skills, providing
      adequate attention to the patient, providing a safe environment that maintains
      privacy and provides a sense of well-being are important actions that are well
      within the control of individual anesthesia providers and may lead to improved
      care from the perception of the patient.

PMID- 25608428
TI  - Exploratory factor analysis of the 12-item Functional Assessment of Chronic
      Illness Therapy-Spiritual Well-Being Scale in people newly diagnosed with
      advanced cancer.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to reexamine the factor
      pattern of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual
      Well-Being Scale (FACIT-Sp-12) using exploratory factor analysis in people newly
      diagnosed with advanced cancer. METHODS: Principal components analysis (PCA) and
      3 common factor analysis methods were used to explore the factor pattern of the
      FACIT-Sp-12. Factorial validity was assessed in association with quality of life
      (QOL). RESULTS: Principal factor analysis (PFA), iterative PFA, and maximum
      likelihood suggested retrieving 3 factors: Peace, Meaning, and Faith. Both Peace
      and Meaning positively related to QOL, whereas only Peace uniquely contributed to
      QOL. CONCLUSION: This study supported the 3-factor model of the FACIT-Sp-12.
      Suggestions for revision of items and further validation of the identified factor
      pattern were provided.

PMID- 25608429
TI  - Measuring nursing error: psychometrics of MISSCARE and practice and professional
      issues items.
AB  - BACKGROUND AND PURPOSE: Health care error causes inpatient morbidity and
      mortality. This study pooled the items from preexisting nursing error
      questionnaires and tested the psychometric properties of modified subscales from
      these item combinations. METHODS: Items from MISSCARE Part A, Part B, and the
      Practice and Professional Issues were collected from 556 registered nurses.
      Principal component analyses were completed for items measuring (a) nursing error
      and (b) antecedents to error. RESULTS: Acceptable factor loadings and internal
      consistency reliability (.70-.89) were found for subscales Acute Care Missed
      Nursing Care, Errors of Commission, Workload, Supplies Problems, and
      Communication Problems. CONCLUSIONS: The findings support the use of 5 subscales
      to measure nursing error and antecedents to error in various inpatient unit types
      with acceptable validity and reliability. The Activities of Daily Living (ADL)
      Omissions subscale is not appropriate for all inpatient unit types.

PMID- 25608431
TI  - Validation of the Brazilian version of the Newcastle Satisfaction with Nursing
      Scales: a partial least squares path modeling approach.
AB  - BACKGROUND AND PURPOSE: Assessing patient satisfaction requires reliable and
      valid instruments. This study evaluated the reliability and validity of the
      Brazilian version of the Newcastle Satisfaction with Nursing Scales (B-NSNS).
      METHODS: This cross-sectional study enrolled 351 adult inpatients. Partial least
      squares path modeling (PLS-PM) approach was used to evaluate the reliability and
      validity of this instrument. RESULTS: After the adjustments of model, both
      constructs exhibited adequate convergent and discriminant validity, showing that
      experiences with nursing care have a significant effect on patient satisfaction
      (r = .70) and account for 49.1% of the variance in patient satisfaction with the
      nursing care (R2 = 0.49). CONCLUSIONS: The B-NSNS result in a valid and reliable
      measure for use in managing nursing care.

PMID- 25608430
TI  - Validation of the NE1 wound assessment tool to improve staging of pressure ulcers
      on admission by registered nurses.
AB  - BACKGROUND AND PURPOSE: There is a need for a simple bedside tool to improve the
      ability of nurses to identify skin alterations, describe wounds, and stage
      pressure ulcers for proper care management and present on admission
      documentation. This study tests the test-retest reliability and criterion
      validity of the NE1 Wound Assessment Tool (NE1 WAT), a single-use tool featuring
      wound pictures and stage descriptions according to National Pressure Ulcer
      Advisor Panel criteria. METHODS: Registered nurses (N = 94) identified and staged
      30 wound photographs under 3 test conditions: (a) without NE1 WAT, (b) with NE1
      WAT after viewing a 10-min instructional presentation, (c) with NE1 WAT but no
      additional instruction after a 7-14-day delay. RESULTS: Out of a possible 90
      points, scores increased 12.3 points between Tests 1 and 2 (p <.001) and 14.1
      points between Tests 1 and 3 (p < .001). Test-retest reliability was high:
      intraclass correlation coefficient (ICC; 3, 1) = .892 (95% confidence interval
      [CI]: 0.840-0.927). CONCLUSIONS: The NE1 WAT is a simple tool that, with little
      training, improved the skin assessment ability of registered nurses.

PMID- 25608432
TI  - Designing and validity evaluation of Quality of Nursing Care Scale in Intensive
      Care Units.
AB  - BACKGROUND AND PURPOSE: Quality of nursing care measurement is essential in
      critical care units. The aim of this study was to develop a scale to measure the
      quality of nursing care in intensive care units (ICUs). METHODS: The 68 items of
      nursing care standards in critical care settings were explored in a literature
      review. Then, 30 experts evaluated the items' content validity index (CVI) and
      content validity ratio (CVR). Items with a low CVI score (< 0.78) and low CVR
      score (< 0.33) were removed from the scale. RESULTS: The 50 items remained in the
      scale. The Scale level-CVI and Scale level-CVR were 0.898 and 0.725,
      respectively. CONCLUSION: The nursing care scale in ICU (Quality of Nursing Care
      Scale- ICU) that was developed in this research had acceptable CVI and CVR.

PMID- 25608433
TI  - Reliability and validity of the Chinese versions of self-efficacy and outcome
      expectations for osteoporosis medication adherence scales in Chinese immigrants.
AB  - BACKGROUND AND PURPOSE: To assess the psychometric properties of Chinese versions
      self-efficacy and outcome expectations on osteoporosis medication adherence
      (SEOMA-C and OEOMA-C) scales. METHODS: Back-translated tools were assessed by
      internal consistency and R2 by structured equation modeling, confirmatory factor
      analyses, hypothesis testing, and criterion-related validity among 110 (81
      females, 29 males) Mandarin-speaking immigrants (mean age = 63.44, SD = 9.63).
      RESULTS: The Cronbach's alpha for SEOMA-C and OEOMA-C is .904 and .937,
      respectively. There was fair and good fit of the measurement model to the data.
      Previous bone mineral density (BMD) testing, calcaneus BMD, self-efficacy for
      exercise, and osteoporosis medication adherence were positively related to SEOMA
      C scores. CONCLUSION: These scales constitute some preliminary validity and
      reliability. Further refined and cultural sensitive items could be explored and
      added.

PMID- 25608434
TI  - Instrument to measure health literacy about complementary and alternative
      medicine.
AB  - BACKGROUND AND PURPOSE: Health literacy is an essential skill for today's health
      care consumers. The growth in use of complementary and alternative medicine (CAM)
      adds to the complexity of being sufficiently health literate. The purpose of this
      article is to describe the initial psychometric evaluation of the "Montana State
      University (MSU) CAM Health Literacy Scale," a newly developed instrument to
      measure an individual's health literacy about CAM. METHODS: Exploratory factor
      analyses, reliabilities, and conceptual considerations were used. RESULTS: The
      outcome is a 21-item instrument with Cronbach's alpha of .753 and 42.27%
      explained variance. Convergent validity assessments revealed weak but significant
      correlations between the scale and measures of general health literacy.
      CONCLUSIONS: The MSU CAM Health Literacy Scale has promise for use in future
      research and clinical endeavors.

PMID- 25608435
TI  - Psychometric testing of the Modified Reminiscence Functions Scale.
AB  - BACKGROUND AND PURPOSE: The Modified Reminiscence Functions Scale (MRFS) measures
      the patterns and functions of reminiscence. The purpose of this study was to
      examine the factor structure of the MRFS in a sample of community-dwelling Black
      adults. METHODS: A convenience sample (N = 335) of Black adults from the
      Northeast completed the 39-item MRFS. Seven- and 8-factor models were evaluated
      given the uncertainty regarding the number of factors in previous reminiscence
      research. RESULTS: Confirmatory factor analysis established validity of the 7
      factor model (relative chi-square [chi2/df] = 1.9, Tucker-Lewis index [TLI] =
      .919, comparative fit index [CFI] = .929, root mean square error of approximation
      [RMSEA] = .05). Reliability of the subscales ranged from .64 to .90. CONCLUSIONS:
      The MRFS is a reliable and valid measure of reminiscence patterns and functions
      in Black adults with similar characteristics.

PMID- 25608436
TI  - Validation of the Center for Epidemiologic Studies Depression Scale in black
      single mothers.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the factor
      structure of the Center for Epidemiologic Studies Depression (CES-D) scale in a
      community sample of Black single mothers and to evaluate the scale's construct
      validity. METHODS: Principal components and exploratory factor analysis were
      used. The participants responded to the CES-D scale and Spielberger's State-Trait
      Anger Expression Inventory. RESULTS: The final sample consisted of 208 Black
      single mothers aged 18-45 years. A 2-factor structure was accepted. Construct
      validity was confirmed via significant correlations with the anger scales. A
      method artifact for the 2-factor solution was ruled out. CONCLUSION: The CES-D
      scale is valid for use with Black single mothers. Additional psychometric
      evidence for the CES-D for Black single mothers is warranted.

PMID- 25608437
TI  - [A study on the 1946 smallpox epidemic in Japan and measures taken against it].
AB  - In early 1946, immediately after World War II, there was a smallpox epidemic in
      Japan. In this paper we investigated trends in the occurrence of smallpox by week
      and region using official documents of the General Headquarters, Supreme
      Commander for the Allied Powers (GHQ/SCAP), which are stored in the National Diet
      Library Modern Japanese Political History Materials Room, and summarized the
      measures taken against this epidemic. The following two points were clarified: 1)
      The 1946 smallpox epidemic peaked in Week 13 (March 24-30; 1,405 new patients),
      and the highest morbidity during this epidemic was seen in Hyogo Prefecture,
      followed by Osaka Prefecture, Aichi Prefecture, Tokyo Prefecture, and Hokkaido
      Prefecture. 2) Measures taken against this epidemic were classified into the
      following three stages: 1. "Vaccine shortage/Manufacture acceleration stage," 2.
      "Vaccine sufficiency/Smallpox vaccination program implementation stage," and 3.
      "Detection of defects in vaccination technique/Reimplementation of the smallpox
      vaccination program stage".

PMID- 25608438
TI  - [Soeda Gensyun; the official doctor of the Tokugawa Court, its medicine and
      medical activity].
AB  - Soeda Genshun was one of 83 founders of the Otamagaike Vaccination Institution.
      This paper summarizes his biography, based on Soeda Genshun's diary. Soeda
      Genshun, was born in 1826, served in Igakukan, Seiyo Igakusho and Igakusho as the
      official doctor. He furnished some money for the establishment of the Otamagaike
      Vaccination Institution and then served as the vaccinator. Soeda's medicine
      transfered gradually to Dutch medicine from Kanran Secchu Igaku.

PMID- 25608439
TI  - A correlative STS: lessons from a Chinese medical practice.
AB  - How might Science and Technology Studies learn more from the intersection between
      'Western' and 'other' forms of knowledge? In this article, we use Eduardo
      Viveiros de Castro's writing on equivocal translation to explore a moment of
      encounter in a Chinese Medical consultation in Taiwan in which a practitioner
      hybridizes Chinese Medicine and biomedicine. Our description is symmetrical, but
      creates a descriptive equivocation in which 'Western' analytical terms are used
      to describe a 'Chinese' medical reality. Drawing on the history of Chinese
      Medicine, we argue that the latter is not analytical, but 'correlative' in a
      specifically 'Chinese' manner that explores patternings, flows, and propensities
      in local collections of things and symptoms. In particular, it both handles
      difference without seeking to unearth stable causal mechanisms and absorbs new
      elements including relevant features of biomedicine. We conclude by briefly
      considering the scope of a possible post-colonial and 'correlative' STS and show
      that a 'correlative' description of the same Chinese Medical consultation would
      differ markedly from one making use of 'Western' analytical assumptions.

PMID- 25608440
TI  - Advancing science diplomacy: Indonesia and the US Naval Medical Research Unit.
AB  - Science diplomacy supposedly builds international cooperation through scientific
      and technical exchange. In practice, however, there are important but often
      overlooked instances where it might create conflict instead--as with accusations
      of espionage surrounding the US Naval Medical Research Unit 2 (NAMRU-2) in
      Indonesia. Did American science diplomacy backfire in Indonesia and, if so, why?
      Most literature fails to anticipate this possibility, let alone explain it, since
      science diplomacy is rarely subject to critical analysis. Rather than shun
      politics or, similarly, simply blame the demise of NAMRU-2 on the military or
      avian influenza, I consider both the successes and failures of this research unit
      in the context of Indonesia's transition to democracy and America's legacy from
      the Cold War. Based on this history, I propose that the effects of science
      diplomacy depend on strategic communication and exchange, as well as elite
      influence and material incentives. Therefore, by challenging the conventional
      wisdom about science diplomacy, NAMRU-2 can help advance the theory and practice
      of this potentially useful tool of statecraft.

PMID- 25608441
TI  - Places of pharmaceutical knowledge-making: global health, postcolonial science,
      and hope in South African drug discovery.
AB  - This article draws on ethnographic research at iThemba Pharmaceuticals, a small
      South African startup pharmaceutical company with an elite international
      scientific board. The word 'iThemba' is Zulu for 'hope', and so far drug
      discovery at the company has been essentially aspirational rather than actual.
      Yet this particular place provides an entry point for exploring how the location
      of the scientific knowledge component of pharmaceuticals--rather than their
      production, licensing, or distribution--matters. The article explores why it
      matters for those interested in global health and postcolonial science, and why
      it matters for the scientists themselves. Consideration of this case illuminates
      limitations of global health frameworks that implicitly posit rich countries as
      the unique site of knowledge production, and thus as the source of unidirectional
      knowledge flows. It also provides a concrete example for consideration of the
      contexts and practices of postcolonial science, its constraints, and its promise.
      Although the world is not easily bifurcated, it still matters who makes knowledge
      and where.

PMID- 25608442
TI  - Zapatista corn: a case study in biocultural innovation.
AB  - In November 2001, Nature published a letter in which University of California
      Berkeley's biologists claimed to have found evidence of genetically modified (GM)
      DNA in regional varieties of maize in Oaxaca, even though the Mexican government
      had banned transgenic corn agriculture in 1998. While urban protesters marched
      against the genetic 'contamination' of Mexican corn by US-based agricultural
      biotech firms, rural indigenous communities needed a framework for understanding
      concepts such as GM before they could take action. This article analyzes how the
      indigenous organization, the Zapatistas, mobilized a program to address this
      novel entity. Their anti-GM project entailed educating local farmers about
      genetics, importing genetic testing kits, seed-banking landrace corn and sending
      seeds to 'solidarity growers' around the world. This article explores material
      semiotic translations to explain one of the central aspects of this project, the
      definition and circulation of Zapatista corn--an entity defined not only through
      cultural geography, but also technological means. Through its circulation,
      Zapatista corn serves to perform a biocultural engagement with Zapatista's
      political project of resistance to neoliberalism. While much has been written
      about both regulatory policy and consumer activism against GM in the Global
      North, Zapatista corn also provides a case study in indigenous, anti-GM activism
      founded on biocultural innovation and the creation of alternative networks for
      circulating corn.

PMID- 25608443
TI  - Genetic fallout in biocultural landscapes: molecular imperialism and the cultural
      politics of (not) seeing transgenes in Mexico.
AB  - This article explores the trajectory of the global controversy over the
      introgression (or not) of transgenes from genetically modified maize into Mexican
      indigenous maize landraces. While a plurality of knowledge-making processes were
      deployed to render transgenes visible or invisible, we analyze how a particular
      in vitro based DNA-centered knowledge came to marginalize other forms of
      knowledge, thus obscuring other bio-cultural dimensions key to the understanding
      of gene flow and maize diversity. We show that dominant molecular norms of proof
      and standards of detection, which co-developed with the world of industrial
      monocropping and gene patenting, discarded and externalized non-compliant actors
      (i.e. complex maize genomes, human dimensions of gene flow). Operating in the
      name of high science, they hence obscured the complex biological and cultural
      processes that maintain crop diversity and enacted a cultural-political
      domination over the world of Mexican landraces and indigenous communities.

PMID- 25608444
TI  - Listening in the Pakal controversy: a matter of care in Ancient Maya studies.
AB  - This article explores the fraught historical politics of a 20th-century
      controversy over a Classic Maya king. The controversy ostensibly concerned the
      age at death of a ruler discovered in 1952 in an elaborate sarcophagus at the
      Mexican site of Palenque. Combining osteological and epigraphic techniques,
      Mexican scholars estimated that the ruler died at about 40 or 50years of age. Two
      decades later, an emerging collective of US hieroglyph experts claimed to have
      determined the grammatical structure of Maya glyphs for the first time and
      reevaluated the sarcophagus inscriptions. They concluded that the king, given the
      name 'Pakal', lived a remarkably long life of 80years (603-683 CE). This reading
      sparked a controversy that would persist until 1999. At stake was not just how to
      tell the story of an ancient Maya lord, but who could tell it, with what
      evidence, and with what degree of certainty. The inclination of some Mexican
      archaeologists to adopt nationalist and Marxist orientations came into palpable
      tension with foreign scholars' liberal, universalist knowledge practices. To
      address this problem, I rethink Pakal's material mediation through bones and
      inscriptions as a 'matter of concern' (Bruno Latour) and 'matter of care' (Maria
      Puig de la Bellacasa). I show how these concepts facilitate the reconsideration
      of contradictory historical propositions as potential sites of coexistence among
      actors temporarily ill equipped to listen to each other's claims. Ultimately, I
      present 'listening' as a technique of cosmopolitical care that complements the
      extensive emphasis on speech and spokespersonship in Latourian cosmopolitics.

PMID- 25608445
TI  - Use of small bowel capsule endoscopy in patients with chronic kidney disease:
      experience from a University Referral Center.
AB  - BACKGROUND: There are only few reports on the diagnostic yield (DY) of small
      bowel capsule endoscopy (SBCE) in patients with chronic kidney disease (CKD). We
      aim to report our SBCE experience in patients with CKD. METHODS: Retrospective
      study; case notes of patients with low estimated glomerular filtration rate
      (eGFR) who underwent SBCE (March 2005-August 2012) for anemia and/or obscure
      gastrointestinal bleeding (OGIB) were retrieved and abstracted. Severity of CKD
      was defined according to Renal Association recommendations as: stage 3 (eGFR: 30
      59); stage 4 (eGFR: 15-29); and stage 5 (eGFR <15 or on dialysis). RESULTS: In
      the aforementioned period, 69 patients with CKD [stage 3: 65/69 (92.8%), stage 4
      or 5:4/69 (7.2%)] had SBCE. 51/65 (78.5%) patients with stage 3 CKD had SBCE due
      to unexplained anemia and/or OGIB [43 (66.1%) and 8 (12.3%), respectively]. In
      25/51 (49%), the SBCE was normal and in 17/51 (33.3%) showed small-bowel
      angiectasias. Other findings were active bleeding (n=2), fold edema (n=2), ileal
      erosions (n=1), adenocarcinoma (n=1), and inconclusive/videos not available
      (n=3). All patients (n=4) with CKD grade 4 or 5 were referred due to unexplained
      anemia; 3/4 (75%) had angiectasias and 1 normal SBCE. Fecal calprotectin (FC) was
      measured in 12 patients with CKD stage 3 and unexplained anemia prior to their
      SBCE; no significant small-bowel inflammation was found in this subgroup.
      CONCLUSION: SBCE has limited DY in CKD patients referred for unexplained anemia.
      Sinister SB pathology is rare, while the most common finding is angiectasias.
      Furthermore, FC measurement prior to SBCE -in this cohort of patients- is not
      associated with increased DY.

PMID- 25608447
TI  - Guideline adherence and health outcomes in diabetes mellitus type 2 patients: a
      cross-sectional study.
AB  - BACKGROUND: The complex disease of diabetes mellitus type 2 (T2DM) requires a
      high standard of quality of care. Clinical practice guidelines define norms for
      diabetes care that ensure regular monitoring of T2DM patients, including annual
      diagnostic tests. This study aims to quantify guideline adherence in Dutch
      general practices providing care to T2DM patients and explores the association
      between guideline adherence and patients' health outcomes. METHODS: In this cross
      sectional study, we studied 363 T2DM patients in 32 general practices in 2011 and
      2012. Guideline adherence was measured by comparing structure and process
      indicators of care with recommendations in the national diabetes care guideline.
      Health outcomes included biomedical measures and health behaviours. Data was
      extracted from medical records. The association between guideline adherence and
      health outcomes was analysed using hierarchical linear and logistic regression
      models. RESULTS: Guideline adherence varied between different recommendations.
      For example 53% of the practices had a system for collecting patient experience
      feedback, while 97% had a policy for no-show patients. With regard to process
      indicators of care, guideline adherence was below 50% for foot, eye and urine
      albumin examination and high (>85%) for blood pressure, HbA1c and smoking
      behaviour assessment. Although guideline adherence varied considerably between
      practices, after adjusting for patient characteristics we found guideline
      adherence not to be associated with patients' health outcomes. CONCLUSIONS:
      Guideline adherence in Dutch general practices offering diabetes care was not
      optimal. Despite considerable variations between general practices, we found no
      clear relationship between guideline adherence and health outcomes. More research
      is needed to better understand the relationship between guideline adherence and
      health outcomes, specifically for guidelines that are based on limited scientific
      evidence.

PMID- 25608448
TI  - A unique cis-3-hydroxy-l-proline dehydratase in the enolase superfamily.
AB  - The genome of Labrenzia aggregata IAM 12614 encodes an uncharacterized member of
      the muconate lactonizing enzyme (MLE) subgroup of the enolase superfamily
      (UniProt ID A0NXQ8 ). The gene encoding A0NXQ8 is located between genes that
      encode members of the proline racemase superfamily, 4R-hydroxyproline 2-epimerase
      (UniProt ID A0NXQ7 ; 4HypE) and trans-3-hydroxy-l-proline dehydratase (UniProt ID
      A0NXQ9 ; t3LHypD). A0NXQ8 was screened with a library of proline analogues; two
      reactions were observed with cis-3-hydroxy-l-proline (c3LHyp), competing 2
      epimerization to trans-3-hydroxy-d-proline (1,1-proton transfer) and dehydration
      to Delta(1)-pyrroline-2-carboxylate (beta-elimination; c3LHyp dehydratase), with
      eventual total dehydration. The genome context encoding A0NXQ8 both (1) confirms
      its novel c3LHyp dehydratase function and (2) provides evidence for metabolic
      pathways that allow L. aggregata to utilize several isomeric 3- and 4
      hydroxyprolines as sole carbon sources. 

PMID- 25608449
TI  - Characteristics and factors related to quality of life in Mexican Mestizo
      patients with celiac disease.
AB  - BACKGROUND: Celiac disease (CD) is a global health problem and its prevalence is
      underestimated, especially in Latin American populations. Our aim was to evaluate
      the clinical features, psychological factors, and health-related quality of life
      (QoL), before and after diagnosis, in a representative sample of adult Mexican
      Mestizo patients presenting with CD. METHODS: A cross-sectional analysis was
      conducted on patients seen at two tertiary referral centers in Mexico. QoL before
      and after CD diagnosis was evaluated using the EuroQoL 5D, the Hospital Anxiety
      and Depression Scale (HADS), and the disease-specific Celiac Symptom Index (CSI)
      questionnaires. RESULTS: We included 80 patients (80% were women, with a mean age
      of 48.6 +/- 14.1 years). The most common symptoms were diarrhea (86%), bloating
      (77.5%), and abdominal pain (71.3%). Mean symptom duration was 10.33 +/- 6.3
      years. Fifty-one patients (63.8%) had a previous diagnosis of irritable bowel
      syndrome (IBS) and 23 (28.8%) had one of functional dyspepsia. Questionnaire
      respondents rated their health status at 50% before diagnosis (0 = worst
      imaginable state, 100 = best imaginable state) and there was a significant
      improvement of 26% after diagnosis. Thirty-nine percent of the patients had a CSI
      score > 45 and they were the ones that had been previously diagnosed most often
      with IBS (p = 0.13) or dyspepsia (p = .036). CONCLUSIONS: At the time of
      diagnosis, Mexican Mestizo patients with CD had poor QoL. Long-standing symptoms
      and a previous diagnosis of functional disorders were associated with worse QoL.
      As in other populations, our results support the need for a detailed examination
      of cost-effective strategies for increasing CD awareness in clinical practice.

PMID- 25608450
TI  - Investigation of the optimal b-value to detect breast tumors with diffusion
      weighted imaging by 1.5-T MRI.
AB  - BACKGROUND: Previous studies have reported that the signal attenuation of
      diffusion-weighted magnetic resonance imaging (DWI) for normal breast tissue and
      tumor were well fitted by a monoexponential and a biexponential function,
      respectively. The aim of this study was to investigate the optimal b-value to
      detect breast tumors from DWI signal attenuations. METHODS: Sixty-four subjects
      with breast cancer underwent DWI using six b-values up to 3500 s/mm2. The signal
      attenuations of normal breast and tumor were fitted by mono- and biexponential
      functions, respectively. The maximum contrast b-values were estimated and
      compared in terms of frequency. RESULTS: In almost all cases, the contrast
      increased with a b-value from 0 to approximately 1500 s/mm2. For b > 1500 s/mm2,
      the contrast decreased. The highest contrast b-value in the range of 0 to 2500
      s/mm2 most frequently was b = 1500 and the next most frequent was 1400 s/mm2.
      Comparing sensitivity and specificity between b = 700 and b = 1400 s/mm2, b =1400
      s/mm2 was slightly superior. CONCLUSION: Based on these results, DWI with a b
      value of approximately 1400-1500 s/mm2 is recommended for optimizing breast tumor
      detectability.

PMID- 25608451
TI  - The usefulness of carvedilol and nebivolol in preventing contrast nephropathy in
      rats.
AB  - BACKGROUND: Oxidative stress and vasoconstriction appear to be important
      components of contrast nephropathy (CN) pathogenesis, and both carvedilol and
      nebivolol are known to have vasodilatory and antioxidant effects. AIMS: This
      study aimed to investigate whether carvedilol and nebivolol play preventive roles
      against developing CN and to compare the effects of each. MATERIALS AND METHODS:
      Wistar albino rats were divided into control (C, n = 6), contrast material (CM, n
      = 6), carvedilol (CV, n = 7), carvedilol + contrast material (CV + CM, n = 7),
      nebivolol (N, n = 7), and nebivolol + contrast (N + CM, n = 7) groups. Following
      3 days of dehydration, 6 mL/kg diatrizoate was administered to each rat.
      Carvedilol was given at a dose of 2 mg/kg and nebivolol at a dose of 1 mg/kg by
      way of oral gavage. After scarification, total antioxidant capacity (TAC),
      malondialdehyde (MDA), and superoxide dismutase (SOD) were studied in renal
      tissue. Histopathological findings were graded as mild (+), moderate (++), and
      severe (+++). RESULTS AND DISCUSSION: Most of the histopathological findings and
      MDA levels were significantly higher in the CM group than that in the C, CVCM,
      and NVCM groups, whereas there was no significant difference between the C, CVCM
      and NVCM groups. TAC level in the CM group was significantly lower than in all
      other groups. There was no difference in SOD among groups. CONCLUSIONS:
      Carvedilol and nebivolol both prevent development of nephropathy related to CMs
      by decreasing oxidative stress. Neither is superior to the other.

PMID- 25608452
TI  - Comment on: Tamsulosin versus nifedipine in medical expulsive therapy for distal
      ureteral stones.

PMID- 25608453
TI  - Decrease of Urotensin II activity can impact on the volume status in predialysis
      chronic kidney disease.
AB  - Urotensin II (U-II) was thought to be one of the mediators of primary renal
      sodium retention due to effects on renal sodium excretion. For this purpose, the
      relationship between U-II and overhydration was investigated. A total of 107
      patients were enrolled in the study. According to body compositor monitor
      analysis, fluid overload up to 1.1 L, was considered normohydration. Patients
      were divided according to hydration status; overhydrate (n = 42) and normohydrate
      (n = 65) were studied in both groups. Pulse waveform velocity propagation for
      arterial stiffness and blood pressure analysis and echocardiographic left
      ventricular and left atrial indices were performed with known fluid overload
      related parameters. U-II levels were measured by using Human ELISA kit. In
      overhydrated group, U-II levels were significantly lower. All parameters (blood
      pressure, arterial stiffness parameters, echocardiographic data, age, gender,
      diabetes, U-II, hemoglobin) correlated with overhydration, were determined by
      linear regression model (method = enter), when considered together, U-II was
      found to be an independent predictor from other conventional overhydration
      related parameters. Male sex, left ventricular mass index, left atrial volume
      index, hemoglobin value were found to be independent predictors for
      overhydration. Considering the association of low U-II levels with adverse
      cardiovascular events and its role in sodium retention, we think that low U-II
      levels can be accepted as a potential therapeutic target in patients with
      hypervolemic cardio-renal syndrome.

PMID- 25608454
TI  - Prediction of poorly differentiated hepatocellular carcinoma using contrast
      computed tomography.
AB  - BACKGROUND: Percutaneous radiofrequency ablation (RFA) is a well-established
      local treatment for small hepatocellular carcinoma (HCC). However, poor
      differentiation is a risk factor for tumor seeding or intrahepatic dissemination
      after RFA for HCC. The present study aimed to develop a method for predicting
      poorly differentiated HCC using contrast computed tomography (CT) for safe and
      effective RFA. METHODS: Of HCCs diagnosed histologically, 223 patients with 226
      HCCs showing tumor enhancement on contrast CT were analyzed. The tumor
      enhancement pattern was classified into two categories, with and without non
      enhanced areas, and tumor stain that disappeared during the venous or equilibrium
      phase with the tumor becoming hypodense was categorized as positive for washout.
      RESULTS: The 226 HCCs were evaluated as well differentiated (w-) in 56,
      moderately differentiated (m-) in 137, and poorly differentiated (p-) in 33. The
      proportions of small HCCs (3 cm or less) in w-HCCs, m-HCCs, and p-HCCs were 86%
      (48/56), 59% (81/137), and 48% (16/33), respectively. The percentage with
      heterogeneous enhancement in all HCCs was 13% in w-HCCs, 29% in m-HCCs, and 85%
      in p-HCCs. The percentage with tumor stain washout in the venous phase was 29% in
      w-HCCs, 63% in m-HCCs, and 94% in p-HCCs. The percentage with heterogeneous
      enhancement in small HCCs was 10% in w-HCCs, 10% in m-HCCs, and 75% in p-HCCs.
      The percentage with tumor stain washout in the venous phase in small HCCs was 23%
      in w-HCCs, 58% in m-HCCs, and 100% in p-HCCs. Significant correlations were seen
      for each factor (p < 0.001 each). Sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy for prediction of poor
      differentiation in small HCCs by tumor enhancement with non-enhanced areas were
      75%, 90%, 48%, 97%, and 88%, respectively; for tumor stain washout in the venous
      phase, these were 100%, 55%, 22%, 100%, and 60%, respectively. CONCLUSIONS: Tumor
      enhancement patterns were associated with poor histological differentiation even
      in small HCCs. Tumor enhancement with non-enhanced areas was valuable for
      predicting poorly differentiated HCC.

PMID- 25608455
TI  - Derivation of water quality criteria of phenanthrene using interspecies
      correlation estimation models for aquatic life in China.
AB  - Species sensitivity distribution (SSD) method has been widely used to derive
      water quality criteria (WQC). However, the toxicity data of some environmental
      pollutants are not easily accessible, especially for endangered and threatened
      species. Thus, it would be very desirable and economical to predict the toxicity
      of those species not subjected to toxicity test with the aid of a mathematical
      model. The interspecies correlation estimation (ICE) model (developed by the US
      Environmental Protection Agency (USEPA)) uses the initial toxicity estimate for
      one species to produce correlated toxicity values for multiple species, and it
      can be utilized to develop SSD and HC5 (hazardous concentration, 5th percentile).
      In this study, we explored the applicability of ICE to predict toxicity of
      phenanthrene to various species. ICE-based SSDs were generated using three
      surrogate species (Oncorhynchus mykiss, Lepomis macrochirus, and Daphnia magna)
      and compared with the metrical-based SSD. The corresponding HC5 of both models
      were also compared. The results showed there were no significant differences
      between HC5 derived from measured acute and ICE-based predicted values. The ICE
      model was verified as a valid approach for generating SSDs with limited toxicity
      data and deriving WQC for phenanthrene. 

PMID- 25608456
TI  - Acute and chronic toxicity of emerging contaminants, alone or in combination, in
      Chlorella vulgaris and Daphnia magna.
AB  - This work presents the toxicity results of different compounds classified as
      emerging contaminants on primary producers and primary consumers in the aquatic
      compartment. The objectives were to (1) obtain acute and chronic toxicity results
      for algae and Daphnia magna using standardised or currently used tests, (2) study
      the relationship between the effects on the impaired feeding rate for daphnia and
      the effects of reproduction and (3) examine the responses on daphnia and algae
      after binary combinations of environmentally relevant compounds and
      perfluorooctane sulfonate (PFOS). Toxicity data on personal care products (PCPs),
      not reported in the scientific literature up to now, are presented. The results
      confirmed that the Daphnia feeding bioassay can be a sensitive, ecologically
      relevant endpoint to detect sublethal effects and could complement the
      information obtained with the reproduction test on Daphnia. The results also
      suggested that the concomitant occurrence of PFOS and other emerging contaminants
      in the aquatic compartment could affect the toxicity of some compounds according
      to their lipophilicity. 

PMID- 25608457
TI  - Content and quality of information websites about congenital heart defects
      following a prenatal diagnosis.
AB  - BACKGROUND: Pregnant women and their partners use the Internet to search for
      information following a prenatal diagnosis of congenital heart defect. OBJECTIVE:
      Our aim was to explore central subjects of content and to assess the
      accessibility, reliability, usability, and quality of written information on
      publicly available information websites about congenital heart defects following
      a prenatal diagnosis. METHODS: Following searches on Bing and Google, we included
      websites containing patient information in English. Hits ranged from 340,000
      67,500,000 and the first 50 hits from each search were screened for inclusion
      (N=600). Of these hits, 39.3% (236/600) were irrelevant. A total of 67 websites
      were included, of which 37% (25/67) were affiliated with independent information
      websites, 25% (17/67) with charity/private organizations, 25% (17/67) with
      hospitals/clinics, and 13% (8/67) had other affiliations. The majority of the
      websites (76%, 51/67) could not be attributed to an author. A manifest content
      analysis was performed to explore central subjects of content. The DISCERN
      instrument was used to assess the quality of information, and the LIDA tool was
      used to assess accessibility, usability, and reliability of the included
      websites. RESULTS: The content on the majority of the websites included care and
      treatment of children with congenital heart defects (88%, 59/67), causes of
      congenital heart defects (88%, 59/67), symptoms of congenital heart defects (85%,
      57/67), prevalence of congenital heart defects (81%, 54/67), potential
      complications of congenital heart defects (75%, 50/67), prenatal
      diagnostics/screening methods (72%, 48/67), and specific congenital heart defects
      (72%, 48/67), whereas less than 10% included information about termination of
      pregnancy (6%, 4/67), care during pregnancy (5%, 3/67), and information
      specifically directed to partners (1%, 1/67). The mean of the total DISCERN score
      was 27.9 (SD 9.7, range 16-53). According to the instrument, a majority of the
      websites were categorized as very poor regarding information about effects of no
      treatment (88%, 59/67), support for shared decision making (85%, 57/67),
      achievement of its aims (84%, 56/67), explicit aims (82%, 55/67), risks of each
      treatment (82%, 55/67), how treatment choices affect overall quality of life
      (76%, 51/67), and areas of uncertainty (76%, 51/67). The mean of the total LIDA
      score was 92.3 (SD 13.1, range 61-127). According to the tool, a majority of the
      websites were categorized as good with regard to registration (97%, 65/67) and
      browser test (75%, 50/67), whereas a majority were categorized as poor with
      regard to currency (87%, 58/67), content production (84%, 56/67), and
      engagability (75%, 50/67). CONCLUSIONS: Difficulties in finding relevant
      information sources using Web search engines and quality deficits on websites are
      an incentive for health professionals to take an active part in providing
      adequate and reliable information online about congenital heart defects.

PMID- 25608458
TI  - Contemporary Practice Patterns in the Management of Acute Obstructing Ureteral
      Stones.
AB  - PURPOSE: To elucidate current practice patterns among Endourological Society
      members for acutely obstructing ureteral stones necessitating intervention.
      METHODS: A practice pattern survey was sent to members of the Endourological
      Society using Survey Monkey. The following question stem was given: "Patient
      presents to the ER with acute renal colic and intractable pain, no signs of
      infection, i.e. afebrile and no pyuria. Stone is obstructing, and causing
      intractable pain; thus observation or medical expulsive therapy is not
      appropriate." A follow-up stem was provided for specific scenarios: "Calculus
      measuring x mm at x location. What is your preferred management option?" The
      options given for immediate management included shockwave lithotripsy (SWL),
      ureteroscopy (URS), stent placement, or percutaneous management. RESULTS: Four
      hundred and sixteen complete responses of approximately 2000 were received. There
      was a significant difference in management choice based on stone location
      (P<0.001) and stone size (P<0.001). URS was the predominant modality used for
      urgent treatment of acute proximal ureteral stones from 5, 10, and 15 mm except
      for calculi of 20 mm, where the preference was for percutaneous management.
      Immediate URS was the preferred choice for all distal and midureteral stones,
      regardless of size. The use of stents vs percutaneous nephrostomy drainage was
      similar (18% vs 16%, respectively) for proximally obstructing calculi, while
      stent insertion was preferred over nephrostomy for mid and distal stones.
      CONCLUSIONS: Current practice patterns among endourologists indicate a strong
      preference for immediate URS management over stent placement or SWL for acutely
      obstructing ureteral calculi. Not surprisingly, 20-mm stones in the proximal
      ureter had percutaneous management.

PMID- 25608459
TI  - Joint Association of Active and Passive Smoking with Psychiatric Distress and
      Violence Behaviors in a Representative Sample of Iranian Children and
      Adolescents: the CASPIAN-IV Study.
AB  - BACKGROUND: Mental health and smoking have been receiving increasing attention in
      adolescents all over the world. Although some studies have assessed the
      independent association of active/passive smoking with mental health, joint
      association of active and passive smoking with mental health remains unclear.
      PURPOSE: This study was designed to evaluate the joint association of smoking
      status (active and passive smoking) with psychiatric distress and violent
      behaviors in Iranian children and adolescents. METHOD: In this national survey,
      13,486 students, aged 6-18 years, living in rural and urban areas of 30 provinces
      of Iran were selected via multistage, cluster sampling method. Psychiatric
      distress (including worthless, angriness, worrying, insomnia, confusion,
      depression, and anxiety), violence behaviors (including bullying, victim, and
      physical fight), and smoking status (nonsmoker, only passive smoker, only active
      smoker, and active and passive smoker) were assessed. The questionnaire was
      prepared based on the World Health Organization Global School-based Student
      Health Survey (WHO-GSHS). Data were analyzed by the Stata package. RESULTS:
      Psychiatric distress and violent behaviors had linearly positive association with
      smoking status (p trend < 0.001). Compared to "nonsmoker" group, participants who
      were exposed to passive smoking besides active tobacco use were at increased risk
      of having angriness (odds ratio (OR) 2.55, 95 % confidence interval (CI) 1.86
      3.48), worrying (OR 1.66, 95 % CI 1.24-2.20), and anxiety (OR 1.99, 95 % CI 1.52
      2.61) and victim (OR 1.77, 95 % CI 1.34-2.33) and bully behaviors (OR 3.08, 95 %
      CI 2.33-4.07). CONCLUSION: The current findings suggest that active and passive
      tobacco smoking has synergistic effect on psychiatric distress. Since majority of
      smokers with psychiatric distress do not receive mental health services or
      counseling on smoking, strategies to address mental health problems and smoking
      prevention should be included as a part of school health services.

PMID- 25608460
TI  - Dieting Increases the Likelihood of Subsequent Obesity and BMI Gain: Results from
      a Prospective Study of an Australian National Sample.
AB  - BACKGROUND: Diet is a major determinant of obesity; however, findings from the
      studies examining how dieting to lose weight affects weight gain have been
      inconclusive. PURPOSE: Our aim was to examine the longitudinal association of
      frequency of dieting for weight loss with (a) obesity status and (b) body mass
      index (BMI) change. METHODS: We used data from Waves 9 (2009) and 10 (2010) of
      the Household Income and Labour Dynamics in Australia (HILDA) survey. Binominal
      logistic regression estimated the association of frequency of dieting in 2009 on
      probability of obesity in 2010. Multinomial logistic regression estimated the
      association of frequency of dieting in 2009 on the probability of BMI gain versus
      BMI maintenance and BMI loss between 2009 and 2010. The analysis sample size was
      8824. RESULTS: Compared to those who were never on a diet in the previous year,
      the odds of obesity were 1.9, 2.9, and 3.2 times higher among those who were on a
      diet once, more than once, and always, respectively. Similarly, the odds of BMI
      gain versus BMI maintenance and also versus BMI loss were higher among those who
      dieted than those who did not. CONCLUSIONS: Dieting to lose weight can contribute
      to the risk of future obesity and weight gain. Losing weight requires a
      commitment to change one's lifestyle and a sustained effort to maintain a healthy
      diet and engage in physical activity.

PMID- 25608461
TI  - Type D personality, mental distress, social support and health-related quality of
      life in coronary artery disease patients with heart failure: a longitudinal
      observational study.
AB  - BACKGROUND: The relationship between Type D personality and health related
      quality of life (HRQoL) in coronary artery disease patients is becoming more
      established, however, the factors that may explain this association remain
      unclear. The objective of the study was to examine the mediating effects of
      mental distress and social support on the relationship between the Type D
      personality and HRQoL in CAD patients with heart failure. METHODS: A total of 855
      CAD patients with heart failure were assessed on Type D personality, mental
      distress, perceived social support and HRQoL with the following self-administered
      questionnaires: the Type D personality scale - 14, the Hospital Anxiety and
      Depression scale, the Multidimensional Scale of Perceived Social Support and the
      Minnesota Living with Heart Failure Questionnaire. RESULTS: The prevalence of
      Type D personality within the study population was 33.5%. Type D personality,
      anxiety symptoms, depressive symptoms and social support were all found to be
      determinants of decreased HRQoL (p's < 0.001), once age, gender, NYHA functional
      class and acute myocardial infarction were adjusted for. Anxiety, depressive
      symptoms and social support were found to mediate the relationship between Type D
      personality and HRQoL. Type D personality exerted a stable effect on HRQoL over
      24 months follow-up period. CONCLUSIONS: Type D personality has an independent
      significant effect on the HRQoL in CAD patients with heart failure, and this
      relation is mediated by anxiety and depressive symptoms, social support.

PMID- 25608462
TI  - The role of general practice in routes to diagnosis of lung cancer in Denmark: a
      population-based study of general practice involvement, diagnostic activity and
      diagnostic intervals.
AB  - BACKGROUND: Lung cancer stage at diagnosis predicts possible curative treatment.
      In Denmark and the UK, lung cancer patients have lower survival rates than
      citizens in most other European countries, which may partly be explained by a
      comparatively longer diagnostic interval in these two countries. In Denmark, a
      pathway was introduced in 2008 allowing general practitioners (GPs) to refer
      patients suspected of having lung cancer directly to fast-track diagnostics.
      However, symptom presentation of lung cancer in general practice is known to be
      diverse and complex, and systematic knowledge of the routes to diagnosis is
      needed to enable earlier lung cancer diagnosis in Denmark. This study aims to
      describe the routes to diagnosis, the diagnostic activity preceding diagnosis and
      the diagnostic intervals for lung cancer in the Danish setting. METHODS: We
      conducted a national registry-based cohort study on 971 consecutive incident lung
      cancer patients in 2010 using data from national registries and GP
      questionnaires. RESULTS: GPs were involved in 68.3% of cancer patients'
      diagnostic pathways, and 27.4% of lung cancer patients were referred from the GP
      to fast-track diagnostic work-up. A minimum of one X-ray was performed in 85.6%
      of all cases before diagnosis. Patients referred through a fast-track route more
      often had diagnostic X-rays (66.0%) than patients who did not go through fast
      track (49.4%). Overall, 33.6% of all patients had two or more X-rays performed
      during the 90 days before diagnosis. Patients whose symptoms were interpreted as
      non-alarm symptoms or who were not referred to fast-track were more likely to
      experience a long diagnostic interval than patients whose symptoms were
      interpreted as alarm symptoms or who were referred to fast-track. CONCLUSIONS:
      Lung cancer patients followed several diagnostic pathways. The existing fast
      track pathway must be supplemented to ensure earlier detection of lung cancer.
      The high incidence of multiple X-rays warrants a continued effort to develop more
      accurate lung cancer tests for use in primary care.

PMID- 25608463
TI  - Triceps-sparing approach for open reduction and internal fixation of neglected
      displaced supracondylar and distal humeral fractures in children.
AB  - BACKGROUND: Supracondylar humeral fractures are one of the most common skeletal
      injuries in children. In cases of displacement and instability, the standard
      procedure is early closed reduction and percutaneous Kirschner wire fixation.
      However, between 10 and 20 % of patients present late. According to the
      literature, patients with neglected fractures are those patients who presented
      for treatment after 14 days of injury. The delay is either due to lack of medical
      facilities or social and financial constraints. The neglected cases are often
      closed injuries with no vascular compromise. However, the elbow may still be
      tense and swollen with abrasions or crusts. In neglected cases, especially after
      early appearance of callus, there is no place for closed reduction and
      percutaneous pinning. Traditionally, distal humeral fractures have been managed
      with surgical approaches that disrupt the extensor mechanism with less
      satisfactory functional outcome due to triceps weakness and elbow stiffness. The
      aim of this study is to evaluate the outcome of delayed open reduction using the
      triceps-sparing approach and Kirschner wire fixation for treatment of neglected,
      displaced supracondylar and distal humeral fractures in children. MATERIALS AND
      METHODS: This prospective study included 15 children who had neglected displaced
      supracondylar and distal humeral fractures. All patients were completely
      evaluated clinically and radiologically before intervention, after surgery and
      during the follow-up. The follow-up period ranged from 8 to 49 months, with a
      mean period of 17 months. Functional outcome was evaluated according to the Mayo
      Elbow Performance Index (MEPI) and Mark functional criteria. RESULTS: All
      fractures united in a mean duration of 7.2 weeks (range 5-10 weeks) with no
      secondary displacement or mal-union. Excellent results were found at the last
      follow-up in 13 of the 15 patients studied (86.66 %), while good results were
      found in two patients (13.33 %) according to the MEPI scale. According to the
      Mark functional criteria, there was one patient with a fair result (6.66 %).
      CONCLUSION: The results were very satisfactory if compared with traditional
      operative techniques, with many advantages including anatomical reduction and
      fixation of the fractures, avoidance of ulnar nerve injury, preservation of the
      extensor mechanism, decrease in incidence of myositis ossificans around the elbow
      and decrease in post-operative stiffness. LEVEL OF EVIDENCE: IV.

PMID- 25608464
TI  - Use of phosphorus-sorbing materials to remove phosphate from greenhouse
      wastewater.
AB  - High phosphate content in wastewater is currently a major issue faced by the
      North American greenhouse industry. Phosphate-sorbing material filters could
      provide a means of removing phosphate from wastewater prior to discharge to the
      environment, but the characterization of economically viable materials and
      specific recommendations for greenhouse wastewater are not available. Batch and
      column experiments were used to examine the capacity of two calcium-based waste
      materials, basic oxygen furnace slag and a concrete waste material, to remove
      phosphate from greenhouse nutrient solution at varied operating conditions.
      Material columns operating at a hydraulic retention time (HRT) of 3 h
      consistently removed >99% of influent phosphate at a concentration of 60 mg/L
      over repeated applications and demonstrated high phosphate retention capacity
      (PRC) of 8.8 and 5.1 g P/kg for slag and concrete waste, respectively. Both
      materials also provided some removal of the micronutrients Fe, Mn and Zn.
      Increasing HRT to 24 h increased P retention capacity of slag to >10.5 g P/kg but
      did not improve retention by concrete waste. Decreasing influent phosphate
      concentration to 20 mg/L decreased PRC to 1.64 g P/kg in concrete waste columns,
      suggesting fluctuations in greenhouse wastewater composition will affect filter
      performance. The pH of filter effluent was closely correlated to final P
      concentration and can likely be used to monitor treatment effectiveness. This
      study demonstrated that calcium-based materials are promising for the removal of
      phosphate from greenhouse wastewater, and worthy of further research on scaling
      up the application to a full-sized system. 

PMID- 25608465
TI  - AtNPF5.5, a nitrate transporter affecting nitrogen accumulation in Arabidopsis
      embryo.
AB  - Dipeptide (Leu-Leu) and nitrate transport activities of 26 Arabidopsis NPF
      (NRT1/PTR Family) proteins were screened in Saccharomyces cerevisiae and Xenopus
      laevis oocytes, respectively. Dipeptide transport activity has been confirmed for
      2 already known dipeptide transporters (AtNPF8.1 and AtNPF8.3) but none of the
      other tested NPFs displays dipeptide transport. The nitrate transport screen
      resulted in the identification of two new nitrate transporters, AtNPF5.5 and
      AtNPF5.10. The localization of the mRNA coding for NPF5.5 demonstrates that it is
      the first NPF transporter reported to be expressed in Arabidopsis embryo. Two
      independent homozygous npf5.5 KO lines display reduced total nitrogen content in
      the embryo as compared to WT plants, demonstrating an effect of NPF5.5 function
      on the embryo nitrogen content. Finally, NPF5.5 gene produces two different
      transcripts (AtNPF5.5a and AtNPF5.5b) encoding proteins with different N-terminal
      ends. Both proteins are able to transport nitrate in xenopus oocytes. 

PMID- 25608468
TI  - Calculating nuclear magnetic resonance shieldings using systematic molecular
      fragmentation by annihilation.
AB  - SMFA was used to calculate NMR shieldings in a test set of 15 molecules. Level 4
      fragments were found to yield satisfactory results when hydrogen bonding was
      included in the calculations. The utility of additional long range corrections
      was also investigated. It was found that with hydrogen bonding already included,
      ab initio long range corrections were not necessary. Instead, inclusion of the
      McConnell correction for fragments was found to be sufficient. With these
      parameters the algorithm produces MADs of 0.046, 0.26, 0.24 and 1.04 ppm for
      hydrogens, carbons, nitrogens and oxygens respectively. 

PMID- 25608466
TI  - Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker
      for diagnosis of esophageal squamous cell carcinoma.
AB  - BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs)
      were present in the blood of cancer patients and have shown great potential as
      powerful and non-invasive tumor markers. However, little is known about the value
      of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We
      hypothesized that ESCC-related lncRNAs might be released into the circulation
      during tumor initiation and could be utilized to detect and monitor ESCC.
      METHODS: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4
      IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found
      to be differently expressed in esophageal cancer were selected as candidate
      targets for subsequent circulating lncRNA assay. A four-stage exploratory study
      was conducted to test the hypothesis: (1) optimization of detected method to
      accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2)
      evaluation of the stability of circulating lncRNAs in human plasma or serum; (3)
      exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4)
      evaluation the diagnostic power of circulating lncRNAs for ESCC. RESULTS: ESCC
      related lncRNAs were detectable and stable in plasma of cancer patients, and
      derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3,
      HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with
      normal controls. By receiver operating characteristic curve (ROC) analysis, among
      the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic
      performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p <
      0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA
      in combination could provide a more effective diagnosis performance (AUC, 0.926,
      p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this
      combination was effective to detect ESCC at an early stage (80.8%). CONCLUSIONS:
      Plasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the
      combination of POU3F3 and SCCA was more efficient for ESCC detection, in
      particular for early tumor screening.

PMID- 25608467
TI  - Interfering with stem cell-specific gatekeeper functions controls tumour
      initiation and malignant progression of skin tumours.
AB  - Epithelial cancer constitutes a major clinical challenge and molecular mechanisms
      underlying the process of tumour initiation are not well understood. Here we
      demonstrate that hair follicle bulge stem cells (SCs) give rise to well
      differentiated sebaceous tumours and show that SCs are not only crucial in tumour
      initiation, but are also involved in tumour plasticity and heterogeneity. Our
      findings reveal that SC-specific expression of mutant Lef1, which mimics
      mutations found in human sebaceous tumours, drives sebaceous tumour formation.
      Mechanistically, we demonstrate that mutant Lef1 abolishes p53 activity in SCs.
      Intriguingly, mutant Lef1 induces DNA damage and interferes with SC-specific
      gatekeeper functions normally protecting against accumulations of DNA lesions and
      cell loss. Thus, normal control of SC proliferation is disrupted by mutant Lef1,
      thereby allowing uncontrolled propagation of tumour-initiating SCs. Collectively,
      these findings identify underlying molecular and cellular mechanisms of tumour
      initiating events in tissue SCs providing a potential target for future
      therapeutic strategies. 

PMID- 25608469
TI  - Thermal conductivity of skutterudite CoSb3 from first principles: Substitution
      and nanoengineering effects.
AB  - CoSb3-based skutterudites are promising intermediate-temperature thermoelectric
      materials and fundamental understanding of the thermal transport in CoSb3 is
      crucial for further improving its performance. We herein calculate the lattice
      thermal conductivity kappaL of CoSb3 with first-principles methods and conduct a
      comprehensive analysis on phonon mode contribution, relaxation time and mean free
      path (MFP) distributions. The contribution of optical phonons is found to be
      significant (28% at 300 K) and important optical modes usually involve two or
      more pnicogen atoms moving synchronously. The MFP (~135 nm at 300 K)
      corresponding to 50% kappaL accumulation in CoSb3 is much larger than that
      predicted from the kinetic theory (~4 nm), providing an opportunity to reduce
      kappaL by nanoengineering. The effects of elemental substitution and
      nanoengineering on kappaL are therefore investigated. A 10% substitution of Sb by
      As results in 57% reduction of kappaL while the in-plane (cross-plane) kappaL of
      a 50-nm CoSb3 thin film is only 56% (33%) of the bulk kappaL at 300 K. The
      impurity scattering and boundary scattering mainly suppress phonons in different
      frequency regimes. By combining these two effects, kappaL can be reduced by more
      than 70% at 300 K, potentially leading to much improved ZT near room temperature.

PMID- 25608470
TI  - HIV tropism shift: new paradigm on cell therapy strategies for HIV cure.

PMID- 25608471
TI  - Prioritization of new oral hepatitis C therapies for HIV patients.

PMID- 25608472
TI  - [Minimally invasive vs. open surgical procedures in the treatment of prostate
      cancer].

PMID- 25608473
TI  - [Robot-assisted laparoscopic partial nephrectomy: functional and oncological
      outcomes].
AB  - BACKGROUND: In recent years, small renal masses (SRM) have been increasingly
      detected as an incidental finding of radiological or ultrasound studies for other
      indications. Organ-sparing renal tumor resection as open partial nephrectomy
      (OPN) is the international standard for renal tumors <7 cm. RESULTS: Due to
      technical developments, minimally invasive procedures have emerged as an
      alternative to OPN. In experienced hands, conventional laparoscopic partial
      nephrectomy (LPN) has achieved good functional and oncological results comparable
      to OPN. Robot-assisted laparoscopic partial nephrectomy (RAPN) has been performed
      since 2004. Compared to LPN, RAPN provides a faster learning curve, better
      visualization and more versatile instrumentation due to the degrees of freedom of
      the articulated instruments. After about 30 procedures, a level of experience is
      reached, which is characterized by good functional results, less blood loss, and
      shorter warm ischemia time of the kidney as compared to LPN. This can relate to a
      shorter hospital stay and faster recovery. Complications according to the Clavien
      classification are mostly grade I and II and are mainly treated conservatively.
      CONCLUSION: Oncological long-term results are not available yet; so that RAPN
      cannot be considered as an equivalent treatment to LPN and OPN. Until long-term
      evidence is available, decisions regarding the surgical technique for organ
      sparing renal tumor resection will be determined by patient's wishes and
      surgeon's preference.

PMID- 25608475
TI  - A stable Li-deficient oxide as high-performance cathode for advanced lithium-ion
      batteries.
AB  - Monodisperse Li-deficient Li(0.35)Ni(0.2)Co(0.1)Mn(0.7)O(2-x) spinel single
      crystals have been prepared for the first time. The Li-deficient oxide
      surprisingly delivers large reversible capacity (251.3 mA h g(-1)), outstanding
      cycle life and low median-voltage of 2.7 V in the range of 2.0-4.9 V.
      Importantly, high median-voltage (4.4 V) and superior rate capability are also
      obtained from 3.0 to 5.0 V. These results indicate that high-energy or high-power
      density can be achieved by controlling discharge cut-off voltage.

PMID- 25608474
TI  - Muscle metastases: comparison of features in different primary tumours.
AB  - BACKGROUND: Muscle metastases (MM) from solid tumours are rare. The aim of this
      study was to describe radiological features of MM, and to compare their patterns
      in different malignancies. METHODS: A retrospective search in the statistical
      database of our institution revealed 61 cases of MM. Additionally, a
      retrospective search in Pubmed database was performed. Together with our cases
      the present analysis comprises 461 patients (682 MM). RESULTS: MM derived from
      the following malignancies: lung cancer (25.1%), gastrointestinal tumours
      (21.0%), and urological tumours (13.2%). Other neoplasias with MM were rare. MM
      were localised most frequently in the thigh muscles, the extraocular musculature,
      and the gluteal and paravertebral muscles. The localisation of MM was different
      in several primary malignancies. CONCLUSION: MM present with a broad spectrum of
      radiological features. Different CT imaging findings of MM were observed in
      different primary tumours. The localisation of MM also varies with different
      primary malignancies.

PMID- 25608476
TI  - Acceptability and Feasibility of Physical Activity Assessment Methods for an
      Appalachian Population.
AB  - Nowhere is improving understanding and accurate assessment of physical activity
      more important for disease prevention and health promotion than among health
      disparities populations such as those residing in rural and Appalachian regions.
      To enhance accurate assessment of physical activity and potentially improve
      intervention capacity, we conducted a mixed-methods study examining the
      acceptability and feasibility of self-report physical activity questionnaires,
      pedometers, and accelerometers among rural Appalachian children, adolescents, and
      adults. Most participants reported positive experiences with all three physical
      activity assessment tools. Several acceptability ratings differed by age group
      and by sex within each age group. With very few exceptions, no significant
      differences in acceptability were found by race, education, employment status,
      health status, BMI categories, income levels, or insurance status within age
      groups or overall. Several factors may impact the choice of the physical activity
      assessment method, including target population age, equipment cost, researcher
      burden, and potential influence on physical activity levels. Children and
      adolescents appear to have more constraints on when they can wear pedometers and
      accelerometers. While pedometers are inexpensive and convenient, they may
      influence physical activity levels, rather than simply measure them.
      Accelerometers, while less influential on behavior, consume extensive resources,
      including high purchase costs and researcher burden. 

PMID- 25608478
TI  - Development of n-type cobaltocene-encapsulated carbon nanotubes with remarkable
      thermoelectric property.
AB  - Direct conversion from heat to electricity is one of the important technologies
      for a sustainable society since large quantities of energy are wasted as heat. We
      report the development of a single-walled carbon nanotube (SWNT)-based high
      conversion efficiency, air-stable and flexible thermoelectric material. We
      prepared cobaltocene-encapsulated SWNTs (denoted CoCp2@SWNTs) and revealed that
      the material showed a negative-type (n-type) semiconducting behaviour (Seebeck
      coefficient: -41.8 MUV K(-1) at 320 K). The CoCp2@SWNT film was found to show a
      high electrical conductivity (43,200 S m(-1) at 320 K) and large power factor
      (75.4 MUW m(-1) K(-2)) and the performance was remarkably stable under
      atmospheric conditions over a wide range of temperatures. The thermoelectric
      figure of merit (ZT) value of the CoCp2@SWNT film (0.157 at 320 K) was highest
      among the reported n-type organic thermoelectric materials due to the large power
      factor and low thermal conductivity (0.15 W m(-1) K(-1)). These characteristics
      of the n-type CoCp2@SWNTs allowed us to fabricate a p-n type thermoelectric
      device by combination with an empty SWNT-based p-type film. The fabricated device
      exhibited a highly efficient power generation close to the calculated values even
      without any air-protective coating due to the high stability of the SWNT-based
      materials under atmospheric conditions.

PMID- 25608477
TI  - Combined image and genomic analysis of high-grade serous ovarian cancer reveals
      PTEN loss as a common driver event and prognostic classifier.
AB  - BACKGROUND: TP53 and BRCA1/2 mutations are the main drivers in high-grade serous
      ovarian carcinoma (HGSOC). We hypothesise that combining tissue phenotypes from
      image analysis of tumour sections with genomic profiles could reveal other
      significant driver events. RESULTS: Automatic estimates of stromal content
      combined with genomic analysis of TCGA HGSOC tumours show that stroma strongly
      biases estimates of PTEN expression. Tumour-specific PTEN expression was tested
      in two independent cohorts using tissue microarrays containing 521 cases of
      HGSOC. PTEN loss or downregulation occurred in 77% of the first cohort by
      immunofluorescence and 52% of the validation group by immunohistochemistry, and
      is associated with worse survival in a multivariate Cox-regression model adjusted
      for study site, age, stage and grade. Reanalysis of TCGA data shows that
      hemizygous loss of PTEN is common (36%) and expression of PTEN and expression of
      androgen receptor are positively associated. Low androgen receptor expression was
      associated with reduced survival in data from TCGA and immunohistochemical
      analysis of the first cohort. CONCLUSION: PTEN loss is a common event in HGSOC
      and defines a subgroup with significantly worse prognosis, suggesting the
      rational use of drugs to target PI3K and androgen receptor pathways for HGSOC.
      This work shows that integrative approaches combining tissue phenotypes from
      images with genomic analysis can resolve confounding effects of tissue
      heterogeneity and should be used to identify new drivers in other cancers.

PMID- 25608479
TI  - Low levels of LTR retrotransposon deletion by ectopic recombination in the
      gigantic genomes of salamanders.
AB  - Across the tree of life, species vary dramatically in nuclear genome size.
      Mutations that add or remove sequences from genomes-insertions or deletions, or
      indels-are the ultimate source of this variation. Differences in the tempo and
      mode of insertion and deletion across taxa have been proposed to contribute to
      evolutionary diversity in genome size. Among vertebrates, most of the largest
      genomes are found within the salamanders, an amphibian clade with genome sizes
      ranging from ~14 to ~120 Gb. Salamander genomes have been shown to experience
      slower rates of DNA loss through small (i.e., <30 bp) deletions than do other
      vertebrate genomes. However, no studies have addressed DNA loss from salamander
      genomes resulting from larger deletions. Here, we focus on one type of large
      deletion-ectopic-recombination-mediated removal of LTR retrotransposon sequences.
      In ectopic recombination, double-strand breaks are repaired using a "wrong"
      (i.e., ectopic, or non-allelic) template sequence-typically another locus of
      similar sequence. When breaks occur within the LTR portions of LTR
      retrotransposons, ectopic-recombination-mediated repair can produce deletions
      that remove the internal transposon sequence and the equivalent of one of the two
      LTR sequences. These deletions leave a signature in the genome-a solo LTR
      sequence. We compared levels of solo LTRs in the genomes of four salamander
      species with levels present in five vertebrates with smaller genomes. Our results
      demonstrate that salamanders have low levels of solo LTRs, suggesting that
      ectopic-recombination-mediated deletion of LTR retrotransposons occurs more
      slowly than in other vertebrates with smaller genomes.

PMID- 25608481
TI  - Vesicular disruption of lysosomal targeting organometallic polyarginine
      bioconjugates.
AB  - Compounds which are able to destabilize the lysosomal membrane have been proposed
      as interesting candidates for targeted anticancer drugs due to the pronounced
      lysosomal changes in cancer cells. For this purpose, metallocene derivatives of a
      cell penetrating polyarginine peptide M-(Arg)9(Phe)2Lys-NH2 (where M = ferrocene
      carboxylate or ruthenocene carboxylate) were designed and their biological
      activities were investigated in detail. The ferrocenoyl- and ruthenocenoyl
      polyarginine bioconjugates were synthesized via Fmoc solid-phase peptide
      synthesis (SPPS) protocols on a microwave-assisted synthesizer. After HPLC
      purification >98% purity was observed for all conjugates. Their interaction with
      supported biomimetic membranes was investigated on a quartz crystal microbalance
      (QCM) and revealed a very strong binding of the metallocene peptides and their
      metal-free congeners to an artificial eukaryotic membrane model (DMPC
      cholesterol). To demonstrate their antiproliferative utility as cytotoxic
      compounds for a targeted anticancer drug, cell viability (by the crystal violet
      assay), apoptosis (flow cytometry, Ann V/PI staining), induction of reactive
      oxygen species (ROS, by flow cytometry with dihydroethidium staining), and
      changes in cancer cell metabolism, e.g. respiration and glycolysis, were studied.
      Our results reveal only a weak toxicity for the metal-free polyarginine peptide,
      which could be significantly enhanced (to ca. 50 MUM against HeLa cells in the
      best case) by coupling ferrocene or ruthenocene carboxylates to the N-terminus of
      the peptide. The investigation of the cellular uptake and intracellular
      localization by fluorescence microscopy revealed an enhanced vesicular disruption
      by the metallocene bioconjugate compared to the metal-free derivative which could
      be triggered by light and chemicals. Further studies of apoptosis, respiration,
      glycolysis and ROS formation reveal the superior characteristics of the
      metallocene compounds. While most cells remain viable even at 300 MUM of the
      metal free bioconjugate 1, most cells are dead or in late stages of apoptosis at
      200 MUM of the ruthenocene derivative 3, and at 100 MUM of the most active
      ferrocene derivative 2, however, all show very little sign of necrosis. Also, the
      metal free compound 1 does not induce ROS formation but both metallocene
      polyarginine bioconjugates are clearly associated with enhanced intracellular ROS
      levels, with levels for the redox-active ferrocene derivative being two times
      higher than for the structurally very similar but redox-silent ruthenocene
      derivative. We propose that such metallocene-polyarginine peptides induce
      lysosomal membrane permeabilization and thereby could be developed towards
      targeted anticancer drugs.

PMID- 25608480
TI  - Evolutionary relationships among barley and Arabidopsis core circadian clock and
      clock-associated genes.
AB  - The circadian clock regulates a multitude of plant developmental and metabolic
      processes. In crop species, it contributes significantly to plant performance and
      productivity and to the adaptation and geographical range over which crops can be
      grown. To understand the clock in barley and how it relates to the components in
      the Arabidopsis thaliana clock, we have performed a systematic analysis of core
      circadian clock and clock-associated genes in barley, Arabidopsis and another
      eight species including tomato, potato, a range of monocotyledonous species and
      the moss, Physcomitrella patens. We have identified orthologues and paralogues of
      Arabidopsis genes which are conserved in all species, monocot/dicot differences,
      species-specific differences and variation in gene copy number (e.g. gene
      duplications among the various species). We propose that the common ancestor of
      barley and Arabidopsis had two-thirds of the key clock components identified in
      Arabidopsis prior to the separation of the monocot/dicot groups. After this
      separation, multiple independent gene duplication events took place in both
      monocot and dicot ancestors. 

PMID- 25608482
TI  - Assessing catastrophic and impoverishing effects of health care payments in
      Uganda.
AB  - BACKGROUND: Direct out-of-pocket payments for health care are recognised as
      limiting access to health care services and also endangering the welfare of
      households. In Uganda, such payments comprise a large portion of total health
      financing. This study assesses the catastrophic and impoverishing impact of
      paying for health care out-of-pocket in Uganda. METHODS: Using data from the
      Uganda National Household Surveys 2009/10, the catastrophic impact of out-of
      pocket health care payments is defined using thresholds that vary with household
      income. The impoverishing effect of out-of-pocket health care payments is
      assessed using the Ugandan national poverty line and the World Bank poverty line
      ($1.25/day). RESULTS: A high level and intensity of both financial catastrophe
      and impoverishment due to out-of-pocket payments are recorded. Using an initial
      threshold of 10% of household income, about 23% of Ugandan households face
      financial ruin. Based on both the $1.25/day and the Ugandan poverty lines, about
      4% of the population are further impoverished by such payments. This represents a
      relative increase in poverty head count of 17.1% and 18.1% respectively.
      CONCLUSION: The absence of financial protection in Uganda's health system calls
      for concerted action. Currently, out-of-pocket payments account for a large share
      of total health financing and there is no pooled prepayment system available.
      There is therefore a need to move towards mandatory prepayment. In this way,
      people could access the needed health services without any associated financial
      consequence.

PMID- 25608484
TI  - Phototherapy trends in dermatology - light or dark? Correspondence to
      phototherapy trends in dermatology by Luersen et al.

PMID- 25608483
TI  - Transcriptome analysis reveals in vitro cultured Withania somnifera leaf and root
      tissues as a promising source for targeted withanolide biosynthesis.
AB  - BACKGROUND: The production of metabolites via in vitro culture is promoted by the
      availability of fully defined metabolic pathways. Withanolides, the major
      bioactive phytochemicals of Withania somnifera, have been well studied for their
      pharmacological activities. However, only a few attempts have been made to
      identify key candidate genes involved in withanolide biosynthesis. Understanding
      the steps involved in withanolide biosynthesis is essential for metabolic
      engineering of this plant to increase withanolide production. RESULTS:
      Transcriptome sequencing was performed on in vitro adventitious root and leaf
      tissues using the Illumina platform. We obtained a total of 177,156 assembled
      transcripts with an average unigene length of 1,033 bp. About 13% of the
      transcripts were unique to in vitro adventitious roots but no unique transcripts
      were observed in in vitro-grown leaves. A putative withanolide biosynthetic
      pathway was deduced by mapping the assembled transcripts to the KEGG database,
      and the expression of candidate withanolide biosynthesis genes -were validated by
      qRT PCR. The accumulation pattern of withaferin A and withanolide A varied
      according to the type of tissue and the culture period. Further, we demonstrated
      that in vitro leaf extracts exhibit anticancer activity against human gastric
      adenocarcinoma cell lines at sub G1 phase. CONCLUSIONS: We report here a
      validated large-scale transcriptome data set and the potential biological
      activity of in vitro cultures of W. somnifera. This study provides important
      information to enhance tissue-specific expression and accumulation of secondary
      metabolites, paving the way for industrialization of in vitro cultures of W.
      somnifera.

PMID- 25608485
TI  - Hypervascular tumor volume estimated by comparison to a large-scale cerebral
      blood volume radiographic atlas predicts survival in recurrent glioblastoma
      treated with bevacizumab.
AB  - BACKGROUND: Dynamic susceptibility contrast (DSC)-MRI is a well-established
      perfusion MR imaging technique for estimating relative cerebral blood volume
      (CBV) in primary brain tumors; however, tumors localized to regions with
      naturally elevated perfusion, including cortical tissue and common vascular
      territories, make evaluation of tumor vascularity difficult to assess. In the
      current study, we have constructed a large-scale radiographic atlas of CBV to
      assess treatment response to bevacizumab in individual patients with recurrent
      glioblastoma. METHODS: Z-score normalized CBV maps were registered to
      stereotactic atlas space in 450 patients with brain tumors. A CBV atlas was
      created by calculating the voxel-wise mean and variability in CBV. MRI and CBV
      maps from 32 recurrent glioblastoma patients were then obtained prior to and
      following treatment with bevacizumab, registered to and compared with the CBV
      atlas. The volume of tumor tissue with elevated CBV, percentage of enhancing
      tumor with elevated CBV, and the mean and maximum change in normalized CBV
      intensity relative to the atlas were computed. RESULTS: Voxel-wise comparison of
      individual patient CBV maps to the atlas allowed delineation of elevated tumor
      perfusion from artery and normal cortical tissue. An atlas-defined hypervascular
      tumor blood volume greater than 2.35 cc prior to treatment, 0.14 cc after
      treatment, and a decrease in atlas-defined hypervascular tumor volume less than
      80% following treatment were characteristic of a shorter PFS and OS. Traditional
      measures of CBV were not predictive of PFS or OS. CONCLUSIONS: This study
      highlights the advantages of large-scale population maps to identify abnormal
      biological tissues.

PMID- 25608486
TI  - Employment and financial burden of families with preschool children diagnosed
      with autism spectrum disorders in urban China: results from a descriptive study.
AB  - BACKGROUND: Autism spectrum disorder (ASD) affects many aspects of family life,
      such as social and economic burden. Little investigation of this phenomenon has
      been carried out in China. We designed this study to evaluate the employment and
      financial burdens of families with ASD-diagnosed preschoolers. METHODS: Four
      hundred and fifty-nine nuclear families of children with ASD, 418 with some other
      disability (OD) and 424 with typically developing (TD) children were recruited
      for this study. Employment and financial burdens of families were evaluated using
      a structured questionnaire; logistic regression was used to examine differences
      in job change measures by group, and ordinal logistic regression was used to
      investigate the association between household income and group. RESULTS: Fifty
      eight percent of families with ASD children and 19% of families with OD children
      reported that childcare problems had greatly affected their employment decisions,
      compared with 9% of families with TD children (p < 0.001). Age of child, parental
      education and parental age notwithstanding, having a child with ASD and having a
      child with OD were both associated with increased odds of reporting that
      childcare greatly interfered with employment (ASD, OR: 15.936; OD, OR: 2.502; all
      p < 0.001) and decreased the odds of living in a higher-income household (ASD,
      estimate = -1.271; OD, estimate = -0.569; all p < 0.001). The average loss of
      annual income associated with having a child with ASD was Chinese RenMinBi (RMB)
      44,077 ($7,226), compared with RMB 20,788 ($3,408) for families of OD children.
      CONCLUSIONS: ASD is associated with severe employment and financial burdens, much
      more than for OD, in families with preschool children.

PMID- 25608487
TI  - CORR Insights(r): Is there a difference in TKA risk of revision in highly
      crosslinked versus conventional polyethylene?

PMID- 25608488
TI  - Clinical decision-making and patients expectations: is there a link?

PMID- 25608489
TI  - Dialectical behavior therapy skills training reduces binge eating among patients
      seeking weight-management services: preliminary evidence.

PMID- 25608490
TI  - Circumferential esophageal leiomyoma.

PMID- 25608491
TI  - Donor hepatitis C sero-status does not impact survival in liver transplantation.
AB  - BACKGROUND: Liver disease caused by hepatitis C virus (HCV) is the main
      indication for liver transplantation (LT) among adults in the US. Recurrent HCV
      impairs patient and graft survival after LT. The high prevalence of HCV along
      with scarce organs has lead to increased utilization of HCV+ organs. We estimated
      the impact of HCV+ donors on patient and graft survival. MATERIAL AND METHODS: We
      conducted a cohort study of LT recipients age 18 years or older from February
      2002 through December 2012 utilizing UNOS data. We evaluated differences in
      patient characteristics between HCV+ and HCV- recipients. We also compared
      patient and graft survival between these groups and among HCV+ recipients who
      received HCV+ versus HCV- donor organs using the Kaplan-Meier estimator and
      multivariate stratified Cox regression models. RESULTS: We identified 59,899 LT
      recipients. Among those, 1,695 (2.8%) were HCV+ who received HCV+ grafts. HCV+
      recipients of HCV- grafts were more likely to be female, hospitalized, in the
      ICU, on a ventilator, had higher MELD scores, and higher bilirubin. Patient and
      graft survival at 1, 5, and 10 years in HCV+ recipients was inferior to HCV-
      recipients, but HCV+ recipients who received HCV+ versus HCV- grafts were
      equivalent. Multivariate regression revealed multiple variables associated with
      worse outcomes. CONCLUSIONS: The use of HCV+ grafts in HCV+ recipients is not
      associated with worse outcomes. With the increase in HCV+ patients awaiting an
      organ, more consideration should be given to HCV+ donors.

PMID- 25608493
TI  - Characterisation of gastric cancer and its relation to environmental factors: a
      case study in Shenqiu County, China.
AB  - This article presents the results of spatial analysis of gastric cancer and its
      relation to environmental conditions in Shenqiu County, China. Retrospective data
      on gastric cancer mortality (GCM) were analysed at various spatial scales, with
      its relation to environmental factors explored at an appropriate scale. The
      results considered 2 * 2 km(2) grid as the optimal level for characterising GCM
      due to the highest Moran's I (I = 0.68, p < 0.01). Then, three clustering regions
      were clearly identified. Meanwhile, GCM was obviously associated with topography
      (r = -0.11, p < 0.10), farmland (r = 0.11, p < 0.10), population density (r =
      0.10, p < 0.10) and river density (r = 0.11, p < 0.10) in the buffered zones. It
      indicates that spatial grid technique is suitable for characterising GCM in
      Shenqiu County, and that GCM was geographically associated with environmental
      conditions. We suggest that preventive measures for controlling the environment
      related malignant neoplasm should not be limited in the regions suffering from
      this disease but be reasonably extended to surrounding areas. 

PMID- 25608492
TI  - Trends in the surgical management of diverticulitis.
AB  - Sigmoid diverticulitis is an increasingly common Western disease associated with
      a high morbidity and cost of treatment. Improvement in the understanding of the
      disease process, along with advances in the diagnosis and medical management has
      led to recent changes in treatment recommendations. The natural history of
      diverticulitis is more benign than previously thought, and current trends favor
      more conservative, less invasive management. Despite current recommendations of
      more restrictive indications for surgery, practice trends indicate an increase in
      elective operations being performed for the treatment of diverticulitis. Due to
      diversity in disease presentation, in many cases, optimal surgical treatment of
      acute diverticulitis remains unclear with regard to patient selection, timing,
      and technical approach in both elective and urgent settings. As a result, data is
      limited to mostly retrospective and non-randomized studies. This review addresses
      the current treatment recommendations for surgical management of diverticulitis,
      highlighting technical aspects and patterns of care.

PMID- 25608494
TI  - Investigating the CT localizer radiograph: acquisition parameters, patient
      centring and their combined influence on radiation dose.
AB  - OBJECTIVE: To systematically investigate the effect of CT localizer radiograph
      acquisition on the tube current modulation and thus radiation dose of the
      subsequent diagnostic scan. METHODS: Localizer radiographs of an abdominal
      section CT phantom were taken, and the resulting volume CT dose index (CTDIvol)
      for the diagnostic scan was recorded. Variables included tube potential, the
      phantom's alignment within the CT scanner gantry in both the vertical and
      horizontal directions and the X-ray source angle at which the localizer was
      acquired. RESULTS: Diagnostic scan CTDIvol decreased with increasing tube
      potential. Vertical (table height) movement was found to affect radiation dose
      more than horizontal movement, with +/-50 mm table movement resulting in a
      standard deviation in the diagnostic scan CTDIvol of 4.4 mGy, compared with 2.5
      mGy with +/-50 mm horizontal movement. Correspondingly, localizer angles of 90
      degrees  or 270 degrees  (3 o'clock and 9 o'clock X-ray source positions) were
      less sensitive overall to alignment errors, with a standard deviation of 2.5 mGy,
      compared with a 0 degrees  or 180 degrees  angle, which had a standard deviation
      of 3.8 mGy. CONCLUSION: To achieve a consistently optimized radiation dose, the
      localizer protocol should be paired with the diagnostic acquisition protocol. A
      final acquisition angle of 90 degrees  should be used when possible to minimize
      dose variation resulting from alignment errors. ADVANCES IN KNOWLEDGE: Localizer
      parameters that affect radiation output were identified for this scanner system.
      The importance of tube potential and acquisition angle was highlighted.

PMID- 25608495
TI  - A model predicting perforation and complications in paediatric appendicectomy.
AB  - PURPOSE: To analyse the diagnostic value of simple clinical measurements in
      ensuring an early and accurate detection of advanced appendicitis (perforation,
      mass and peri-appendicular abscess) and possible complications. METHODS: A
      retrospective, single-centre study of all paediatric (age 0-14 years)
      appendicectomies was conducted over a 14-year period. Preoperative symptoms,
      signs and laboratory results, intra-operative findings and postoperative
      complications were analyzed. Receiver operating characteristic (ROC) curves were
      used to estimate sensitivity and specificity of significant (p <= 0.05) predictor
      variables based on multivariate logistic regression models. RESULTS: One thousand
      and thirty-seven patients were included. Perforations were seen in 88 (8.5%)
      cases, and abscesses were seen in 35 (3.4%) cases. Of all the clinical variables
      evaluated, preoperative temperature >=37.5  degrees C was most discriminatory for
      advanced appendicitis. Significant other discriminatory clinical variables were
      WBC count >=15,100/MUL, preoperative anorexia and rebound tenderness.
      Postoperative complications occurred in 74 (7.1%) patients and were associated
      with pre-operative temperature >=37.5  degrees C and advanced appendicitis.
      CONCLUSION: Independent clinical predictors of advanced appendicitis exist but
      lack individual accuracy. In this study, preoperative pyrexia is shown to be
      highly associated with both advanced appendicitis and development of
      postoperative complications. This independent factor may point to early need for
      antibiotic treatment, urgent imaging and subsequent intervention in patients with
      appendicitis.

PMID- 25608496
TI  - Increased risk of stroke among patients with Crohn's disease: a population-based
      matched cohort study.
AB  - BACKGROUND: Crohn's disease (CD) is one type of inflammatory bowel disease (IBD)
      that has been speculated to share prognostic factors with the development of
      stroke. There is controversial information in the literature regarding the
      association between CD and stroke. The present cohort study estimated the risk of
      subsequent stroke among CD patients compared with matched comparison subjects
      drawn from a population-based dataset in Taiwan. METHOD: This study drew data
      from the Taiwan National Health Insurance Database to conduct a historical cohort
      study. The study cohort comprised 3309 CD patients, and the comparison cohort
      comprised 13,236 subjects without an IBD. Cox proportional hazards regressions
      were performed to estimate the risk of subsequent stroke during the follow-up
      period. We also conducted additional analyses stratifying by age group and
      gender. RESULTS: After adjusting for selected medical co-morbidities and recent
      prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent
      stroke among patients with CD was found to be 1.911 (95% confidence interval (CI)
      = 1.65-2.22) that of comparison subjects. While we did not detect an association
      between stroke and CD among patients aged 30-40 years, we did detect increased
      risks for stroke among CD patients aged 40-50 years (HR = 2.29) and those aged
      over 50 years (HR = 1.88). We also found women (HR = 2.39) to be at a greater
      risk than men (HR = 1.50). CONCLUSION: This study reports an increased HR for
      subsequent stroke among CD patients when compared to matched comparison patients
      without IBD in an Asian population.

PMID- 25608497
TI  - Supramolecular control of transition metal complexes in water by a hydrophobic
      cavity: a bio-inspired strategy.
AB  - Supramolecular chemistry in water is a very challenging research area. In
      biology, water is the universal solvent where transition metal ions play major
      roles in molecular recognition and catalysis. In enzymes, it participates in
      substrate binding and/or activation in the heart of a pocket defined by the
      folded protein. The association of a hydrophobic cavity with a transition metal
      ion is thus a very appealing strategy for controlling the metal ion properties in
      the very competitive water solvent. Various systems based on intrinsically water
      soluble macrocyclic structures such as cyclodextrins, cucurbituryls, and metallo
      cages have been reported. Others use calixarenes and resorcinarenes
      functionalized with hydrophilic substituents. One approach for connecting a metal
      complex to these cavities is to graft a ligand for metal ion binding at their
      edge. Early work with cyclodextrins has shown Michaelis-Menten like catalysis
      displaying enhanced kinetics and substrate-selectivity. Remarkable examples of
      regio- and stereo-selective transformation of substrates have been reported as
      well. Dynamic two-phase systems for transition metal catalysis have also been
      developed. They rely on either water-transfer of the metal complex through ligand
      embedment or synergistic coordination of a metal ion and substrate hosting.
      Another strategy consists in using metallo-cages, which provide a well-defined
      hydrophobic space, to stabilize metal complexes in water. When the cages can host
      simultaneously a substrate and a reactive metal complex, size- and regio
      selective catalysis was obtained. Finally, construction of a polydentate
      coordination site closely interlocked with a calixarene or resorcinarene
      macrocycle has been shown to be a very fruitful strategy for obtaining metal
      complexes with remarkable hosting properties. For each of these systems, the
      synergism resulting from the biomimetic association of a hydrophobic cavity and a
      metal ion is discussed within the objective of developing new tools for either
      selective molecular recognition (with analytical perspectives) or performant
      catalysis, in water. 

PMID- 25608498
TI  - Synthesis and spectroscopic properties of luminescent tantalum(v)-beta-diketonate
      complexes and their use as optical sensors and the preparation of nanostructured
      Ta2O5.
AB  - This work proposes a simple and inexpensive method to prepare a new series of
      beta-diketonate-tantalum complexes. The method is based on the use of a [TaF7](2
      ) solution, as the tantalum precursor, thenoyltrifluoroacetone (TTA),
      hexafluoroacetylacetone (HFA), and benzoyltrifluoroacetylacetone (BFA) in basic
      medium; basic pH is achieved by adding urea to the reaction medium. Elemental
      analysis, H(1)-NMR spectroscopy, potentiometric measurements conducted with a
      fluorine-selective electrode, conductivity measurements, vibrational spectroscopy
      based on quantum chemistry calculations, and electronic spectroscopy helped in
      determining the molecular structure of the complexes. At room temperature in the
      solid state and in solution upon irradiation with UV light, the complexes
      exhibited blue emission, probably as a result of the heavy atom effect. On the
      basis of the structures, luminescence properties at room temperature, and solvent
      dependent changes in the electronic properties of the complexes, these beta
      diketonates are potentially applicable as optical ethanol or humidity sensors and
      are promising materials for the development of luminescent devices. 

PMID- 25608499
TI  - [Acute treatment of patients with severe traumatic brain injury].
AB  - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and
      permanent disability and a common and important global problem. The contribution
      of secondary posttraumatic brain damage to overall disability in TBI is
      significant, underlining the importance of prompt and comprehensive treatment for
      affected patients. METHODS: This article focuses on current concepts of
      prehospital and emergency room management of patients with severe TBI to prevent
      secondary brain injuries. RESULTS AND DISCUSSION: Preclinical prevention and
      treatment of hypoxia, hypotension and hypercarbia are essential, as they affect
      the long-term outcome in TBI patients. Prehospital intubation should be
      critically weighed and in the context of an individual decision. In general,
      prehospital intubation is more difficult than in the clinical setting. The
      combination of ketamine and benzodiazepines are commonly used to induce
      anesthesia before intubation in hemodynamic instable patients. The choice of a
      muscle relaxant for anesthesia induction is either a non-depolarizing
      neuromuscular blocking agent or succinylcholine. Administration of mannitol or
      hypertonic saline is effective to rapidly decrease intracranial pressure.
      Whenever possible the final destination for transport of TBI patients should be a
      level I center with round the clock neurosurgical expertise. Trauma-induced
      coagulopathy should be recognized and immediately treated using a point-of-care
      testing. CONCLUSION: Hypoxia, hypotension and hypercarbia should strictly be
      avoided to improve survival and neurological outcome in patients with severe TBI.
      The prehospital decision to intubate must be made on a case by case basis at the
      accident site. A level I trauma center should be the destination for this patient
      group.

PMID- 25608500
TI  - [Standardized treatment protocols in acute postoperative pain therapy: analysis
      of contents of standardized medicinal concepts].
AB  - BACKGROUND: Standardized treatment approaches can improve the quality of the
      management of acute postoperative pain. AIM: The purpose of this study was to
      describe the content and structure of currently implemented standards for the
      management of acute postoperative pain in German hospitals and to better define
      the concept of a treatment standard for acute pain. MATERIAL AND METHODS: Written
      standardized treatment protocols from 68 hospitals for the management of acute
      postoperative pain were analyzed. The evaluation was based on the layout of
      processes, the baseline and rescue or on-demand analgesic medication and safety
      mechanisms. RESULTS: A treatment standard per hospital separated for adults (68
      standards) and children (27 standards) was identified and analyzed. A baseline
      medication was provided in all standards for adults and in 89% for children. Of
      the 95 standards 68% routinely combined opioids and non-opioids as a basis (78%
      for adults and 42% for children). A way to adapt the baseline medication was
      described more often in standards for adults. Of the standards for adults 91%
      (85% for children) contained provisions for rescue or on-demand analgesia and
      half of them (both adults and children) included an immediate-release opioid
      formulation, which was readily available. For adults the availability was
      regulated by a predefined process in 29% of the standards (8% for children). In
      cases of persisting pain, repetition of the rescue medication was generally
      possible in 63% of adult standards (54% for children) but within 1 h after the
      first dose in only 43% (30% for children). Intervention limitations for
      application of the rescue medication (e.g., a defined score on the numeric rating
      scale) were set in 63% of adult standards (54% for children). A follow-up
      assessment of the pain intensity after a rescue medication was only required in
      approximately half of the standards and safety information or mechanisms were
      only rarely included. CONCLUSION: Content, structure and type of the evaluated
      treatment standards showed a considerable heterogeneity with respect to the
      availability of rescue and baseline medication. Safety aspects were not addressed
      in many cases. These findings show that despite the requirements of the German
      guidelines for treatment of perioperative and posttraumatic pain for treatment
      standards, there are still no practical recommendations with respect to contents
      and structure of such standards.

PMID- 25608501
TI  - MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and
      virulence in guinea pigs.
AB  - Toxin-antitoxin (TA) systems are highly conserved in members of the Mycobacterium
      tuberculosis (Mtb) complex and have been proposed to play an important role in
      physiology and virulence. Nine of these TA systems belong to the mazEF family,
      encoding the intracellular MazF toxin and its antitoxin, MazE. By overexpressing
      each of the nine putative MazF homologues in Mycobacterium bovis BCG, here we
      show that Rv1102c (MazF3), Rv1991c (MazF6) and Rv2801c (MazF9) induce
      bacteriostasis. The construction of various single-, double- and triple-mutant
      Mtb strains reveals that these MazF ribonucleases contribute synergistically to
      the ability of Mtb to adapt to conditions such as oxidative stress, nutrient
      depletion and drug exposure. Moreover, guinea pigs infected with the triple
      mutant strain exhibits significantly reduced bacterial loads and pathological
      damage in infected tissues in comparison with parental strain-infected guinea
      pigs. The present study highlights the importance of MazF ribonucleases in Mtb
      stress adaptation, drug tolerance and virulence. 

PMID- 25608502
TI  - New technique of local ischemic preconditioning induction without repetitive
      aortic cross-clamping in cardiac surgery.
AB  - BACKGROUND: Several studies have demonstrated that local ischemic preconditioning
      can reduce myocardial ischemia-reperfusion injury in cardiac surgery patients;
      however, preconditioning has not become a standard cardioprotective intervention,
      primarily because of the increased risk of atheroembolism during repetitive
      aortic cross-clamping. In the present study, we aimed to describe and validate a
      novel technique of preconditioning induction. METHODS: Patients undergoing
      coronary artery bypass grafting (12 women and 78 men; mean age, 56 +/- 11 years)
      were randomized into 3 groups: (1) Controls (n = 30), (2) Perfusion (n = 30), and
      (3) Preconditioning (n = 30). All patients were operated under cardiopulmonary
      bypass using normothermic blood cardioplegia. Preconditioning was induced by
      subjecting the hemodynamically unloaded heart to 2 cycles of 3 min of ischemia
      and 3 min of reperfusion with normokalemic blood prior to cardioplegia. In the
      Perfusion group, the heart perfusion remained unaffected for 12 min. Troponin I
      (TnI) levels were analyzed before surgery, and 12, 24, 48 h, and 7 days after
      surgery. The secondary endpoints included the cardiac index, plasma natriuretic
      peptide level, and postoperative use of inotropes. RESULTS: Preconditioning
      resulted in a significant reduction in the TnI level on the 7th postoperative day
      only (0.10 +/- 0.05 and 0.33 +/- 0.88 ng/ml in Preconditioning and Perfusion
      groups, respectively, P < 0.05). In addition, cardiac index was significantly
      higher in the Preconditioning group than in the Control and Perfusion groups just
      after weaning from cardiopulmonary bypass. The number of patients requiring
      inotropic support with >= 2 agents after surgery was significantly lower in the
      Preconditioning and Perfusion group than in the Control group (P < 0.05). No
      complications of the procedure were recorded in the Preconditioning group.
      CONCLUSIONS: The preconditioning procedure described can be performed safely in
      cardiac surgery patients. The application of this technique of preconditioning
      was associated with certain benefits, including improved left ventricular
      function after weaning from cardiopulmonary bypass and a reduced need for
      inotropic support. However, the infarct-limiting effect of preconditioning in the
      early postoperative period was not evident. The procedure does not involve
      repetitive aortic cross-clamping, thus avoiding possible embolic complications.

PMID- 25608504
TI  - [Preventive measures against plague and the control of Chinese coolies in
      colonial Korea].
AB  - This paper aims to examine the preventive measures taken against the plague in
      colonial Korea, particularly as applied to the control of Chinese coolies in
      1911, soon after the annexation. The Government General of Korea began preventive
      measures with a train quarantine in Shin'uiju and Incheon in response to the
      spread of the plague to the Southern Manchuria. Shin' uiju had become urbanized
      due the development of the transportation network, and the seaport of Incheon was
      the major hub for traffic with China. Examining the transportation routes for the
      entry and exit of Chinese to and from Korea makes clear the reason why the Korea
      Government General initiated preventive measures in mid-January, 1911. The
      Government General of Korea tried to block the entry of Chinese through the land
      border crossing with China and through ports of entry, primarily Incheon. During
      the implementation of the preventive measures, quarantine facilities were built,
      including a quarantine station and isolation facility in Incheon. It was also
      needed to investigate the population and residential locations of Chinese in
      Korea to prevent the spread of plague. A certificate of residence was issued to
      all Chinese in Korea, which they needed to carry when they travelled. The
      preventive measures against plague which broke out in Manchuria were removed
      gradually. However, there was no specific measures against Chinese coolies, those
      who had migrated from China to work in the spring in Korea. Still the Government
      General of Korea had doubt about an infection of the respiratory system. As a
      result, the labor market in colonial Korea underwent changes in this period. The
      Government General recruited Korean laborers, instead of Chinese coolies whose
      employment had been planned. This move explains the Government General's strong
      preventive measures against plague and uncertainty in the route of plague
      infection, which influenced subsequent regulations on the prohibition of Chinese
      coolies working on the public enterprise sites and the improvement of labor
      conditions for Korean laborers. 

PMID- 25608503
TI  - Mechanism and functional impact of CD40 ligand-induced von Willebrand factor
      release from endothelial cells.
AB  - Co-stimulation via CD154 binding to CD40, pivotal for both innate and adaptive
      immunity, may also link haemostasis to vascular remodelling. Here we demonstrate
      that human platelet-bound or recombinant soluble CD154 (sCD154) elicit the
      release from and tethering of ultra-large (UL) von Willebrand factor (vWF)
      multimers to the surface of human cultured endothelial cells (ECs) exposed to
      shear stress. This CD40-mediated ULVWF multimer release from the Weibel-Palade
      bodies was triggered by consecutive activation of TRAF6, the tyrosine kinase c
      Src and phospholipase Cgamma1 followed by inositol-1,4,5 trisphosphate-mediated
      calcium mobilisation. Subsequent exposure to human washed platelets caused ULVWF
      multimer-platelet string formation on the EC surface in a shear stress-dependent
      manner. Platelets tethered to these ULVWF multimers exhibited P-selectin on their
      surface and captured labelled monocytes from the superfusate. When exposed to
      shear stress and sCD154, native ECs from wild-type but not CD40 or vWF-deficient
      mice revealed a comparable release of ULVWF multimers to which murine washed
      platelets rapidly adhered, turning P-selectin-positive and subsequently capturing
      monocytes from the perfusate. This novel CD154-provoked ULVWF multimer-platelet
      string formation at normal to fast flow may contribute to vascular remodelling
      processes requiring the perivascular or intravascular accumulation of pro
      inflammatory macrophages such as arteriogenesis or atherosclerosis.

PMID- 25608505
TI  - [Becoming medical doctors in colonial Korea: focusing on the faculty of medical
      colleges in early north Korea].
AB  - This paper traces how Koreans of north area became medical doctors in colonial
      Korea. Most of the past research have focused only on the well-known medical
      doctors, or even when they discussed a great number of doctors, many research
      tended to only pay attention to the explicit final results of those doctors. This
      research, on the other hand, includes ordinary medical doctors as well as the
      renowed ones, and adjusts the focus to the lifetime period of their growth and
      activities. As a result, the misunderstanding and obscurity about the Korean
      medical doctors of north area during this period have been cleared. The new
      characteristics of the Korean medical doctors of this period have been found,
      along with their embodiment of historical significance. At the time, Koreans had
      to get through a number of qualifications in order to become doctors. First is
      the unique background of origin in which the family held interest in the modern
      education and was capable of supporting it financially. Second is the long-term
      status of education that the education from elementary to high school was
      completed without interruption. Third is the academic qualification that among
      various institutions of higher education, medical science was chosen as a major.
      Fourth is the condition of career in which as the career as a doctor had
      consistently continued. Thus, in oder to become a modern medical doctor, Koreans
      had to properly complete these multiple steps of process. The group of Korean
      medical doctors in north area, which was formed after getting through these
      series of process, possessed a number of characteristics. Firstly, as the upper
      middle classes constituted the majority of medical doctors in Korea, the societal
      status of doctors rose and the foundation for the career as a doctor to be
      persisted as the family occupation settled. Secondly, the research career and
      academic degree became the principal method to escape from the discrimination and
      hierarchy existed between doctors. A PhD degree, especially, was the significant
      mark for clearly displaying the abilities and outcomes of the doctors. Lastly,
      the research career, education experience, clinical training and such that the
      Korean doctors of the period had built up were weak at the time, however, they
      were important sources for the future medical science development. Indeed, after
      Liberation, the rapid settlement and growth of Korea's medical science field were
      largely beholden to thus. Therefore, the growth of the Koreans as doctors did not
      cease in colonial Korea, but instead continued onto the history of future
      generations. In spite of the fact that the Korean doctors's growth and activities
      were greatly limited under the forceful policy of colonial domination of the era,
      the efforts the Korean doctors had put were not in vain. Likewise, if we do not
      fix our attention at the dominating policy and system, but rather put together
      the actors' correspondence and struggles of the period, then the Korean doctors
      will be a part of the living history. Hereby, the clue to the paradox between the
      suppression of medical science in colonial Korea and its leap after Liberation
      can be untied. 

PMID- 25608506
TI  - [The life of Choe Ung-sok: with a focus on his design for and role in the health
      care system immediately after the liberation].
AB  - Born in Pyongyang in 1914, Choe Ung-sok was a physician who lived through the
      Japanese colonial era (1910-1945), rule by the United States Army Military
      Government in Korea (USAMGIK; 1945-1948), and national division (1948).
      Influenced by socialism and social hygiene/social medicine during his studies in
      Japan, he played the role of representing the socialist camp in the discussions
      related to the construction of a heath care system immediately following the
      Liberation (1945). His key arguments were: first, the nationalization of the
      medical system and the implementation of nationwide programs to eradicate
      diseases; second, the provision of free medical services through the expansion of
      social insurance; third, the reeducation of the medical personnel; fourth, the
      provision of social sciences education to the medical personnel and the
      reorganization of medicine into preventive medicine; fifth, the nationalization
      of pharmaceutics; sixth, the laborers' establishment of autonomous medical organs
      (affordable clinics, medical consumers' unions through cooperatives); and
      seventh, the reduction of work hours to 6-8 hours, technical improvement, respite
      from research, and guarantee of economic life for the medical personnel.
      Influenced by the medical systems of the Soviet Union and Japan, such arguments
      stood in opposition to the right wing's plan for the construction of a relatively
      passive health care system at the time but, in the end, failed to be realized in
      southern part of Korea under the USAMGIK. Subsequently, he defected to northern
      part of Korea and came to participate in the task of constructing North Korea's
      health care system. Choe's life and design for a health care system provide
      examples through which one can confirm the nature of social hygiene/social
      medicine both during the Japanese colonial era and before and after the
      Liberation and the contents of the design related to a health care system as held
      by the socialist faction. In addition, they show that, immediately after the
      Liberation, there existed a broad spectrum of imagination and arguments
      concerning the desirable health care system. Following the division of the Korean
      Peninsula, South Korea witnessed the instatement of a regime that established
      anti-communism as the state policy and the strong influence of the United States
      in politics, economy, and culture. The consequent frustration of Choe's design
      for a health care system and his defection to North Korea frustrated the creation
      of a National Heath Service (NHS) in South Korea, reinforced the tendency to view
      NHS and social insurance as "socialist" or "communist" methods, and led to the
      restriction of the scope of subsequent discussions related to health care system.
      In conclusion, the course of Choe's life and thought went beyond the life of an
      individual during a period in which diverse ideologies collided through the
      Japanese colonial era, Liberation, and national division and symbolically
      demonstrates one important path of the process of constructing a health care
      system on the Korean Peninsula. 

PMID- 25608507
TI  - [Control discourses and power relations of yellow fever: Philadelphia in 1793].
AB  - 1793 Yellow fever in Philadelphia was the most severe epidemics in the late 18th
      century in the United States. More than 10% of the population in the city died
      and many people fled to other cities. The cause of yellow fever in the United
      States had close relationship with slaves and sugar in Philadelphia. Sugarcane
      plantation had needed many labors to produce sugar and lots of Africans had to
      move to America as slaves. In this process, Aedes aegypti, the vector of yellow
      fever had migrated to America and the circumstances of ships or cities provided
      appropriate conditions for its breeding. In this period, the cause of yellow
      fever could not be established exactly, so suggestions of doctors became
      entangled in political and intellectual discourses in American society. There was
      a critical conflict between Jeffersonian Republicanism and Federalism about the
      origin and treatment of yellow fever. Benjamin Rush, a Jeffersonian Republican,
      suggested urban sanitation reform and bloodletting. He believed the infectious
      disease happened because of unsanitary city condition, so he thought the United
      States could be a healthy nation by improvement of the public health and
      sanitation. He would like to cope with national crisis and develop American
      society on the basis of republicanism. While Rush suggested the improvement of
      public health and sanitation, the city government of Philadelphia suggested
      isolation of yellow fever patients and quarantine. City government isolated the
      patients from healthy people and it reconstructed space of hospital. Also, it
      built orphanages to take care of children who lost their parents during the
      epidemic and implemented power to control people put in the state of exception.
      Of course, city government tried to protect the city and nation by quarantine of
      every ship to Philadelphia. Control policies of yellow fever in 1793 showed
      different conflicts and interactions. Through the yellow fever, Jeffersonian
      Republicanism and Federalism had conflicted in politically, but they had
      interactions for control of the infectious disease. And with these kinds of
      infectious diseases policies, we can see interactions in local, national and
      global level. 

PMID- 25608508
TI  - [A study of development of medicine and science in the nineteenth century science
      fiction: biomedical experiments in Mary Shelley's Frankenstein].
AB  - As the sciences advanced rapidly in the modern European world, outstanding
      achievements have been made in medicine, chemistry, biology, physiology, physics
      and others, which have been co-influencing each of the scientific disciplines.
      Accordingly, such medical and scientific phenomena began to be reflected in
      novels. In particular, Mary Shelley's Frankenstein includes the diverse aspects
      of the change and development in the medicine and science. Associated with
      medical and scientific information reflected in Frankenstein and Frankenstein's
      experiments in the text, accordingly, this research will investigate the aspects
      of medical and scientific development taking place in the nineteenth century in
      three ways. First, the medical and scientific development of the nineteenth
      century has been reviewed by summerizing both the information of alchemy in which
      Frankenstein shows his interest and the new science in general that M. Waldman
      introduces in the text. Second, the actual features of medical and scientific
      development have been examined through some examples of the experimental methods
      that M. Waldman implicitly uttered to Frankenstein. Third, it has been checked
      how the medical and scientific development is related to the main issues of
      mechanism and vitalism which can be explained as principles of life. Even though
      this research deals with the developmental process of medicine & science and
      origin & principles of life implied in Mary Shelley's Frankenstein, its
      significance is that it is the interdisciplinary research focussing on how deeply
      medical and scientific discourse of Mary Shelley's period has been imbedded in
      the nineteenth century novel. 

PMID- 25608509
TI  - The "Oriental" problem: trachoma and Asian immigrants in the United States, 1897
      1910.
AB  - This essay examines the period between 1897 and 1910, when trachoma, a contagious
      eye disease, became an "Oriental" problem that justified exclusionary immigration
      policy against Asians entering the United States. It also investigates the ways
      in which the public fear and alleged threat of the eye disease destabilized and
      undermined the rights of Asian immigrants. Many scholars have explored the link
      between trachoma and southern and eastern European newcomers, in particular Jews,
      but they have not paid much attention to Chinese or Japanese immigrants, for
      whose exclusion trachoma played a significant role. This is primarily because the
      number of Asian immigrants was much smaller than that of their European
      counterparts and because the Chinese Exclusion Acts, which had already been in
      place, functioned as a stronger and more lasting deterrent to Asian immigration
      than exclusion or deportation through medical inspection. Moreover, into the
      1910s, medical and scientific innovations for detecting parasitic diseases (e.g.
      hookworm) helped American authorities exclude Asians in larger numbers. Still,
      the analysis of the discourses surrounding trachoma and immigration from Asia,
      though short-lived, demonstrates the role of medical inspection in controlling
      and regulating Asian immigrants, in particular Chinese and Japanese, into the
      United States and in constructing their legal and political rights. In 1906, the
      fear of trachoma justified an order to segregate Japanese students from white
      children in San Francisco even at the cost of compromising their rights as
      citizens. Along with fierce criticisms against immigration officials by the
      American public, the 1910 investigation of the San Francisco Immigration Office
      problematized the admission of trachoma-afflicted Asian immigrants. Those
      critical of the Immigration Office and its implementation of American immigration
      policy called for exclusionary measures to limit the privileges of exempt classes
      and domiciled aliens and hinder the exertion of their rights to leave and reenter
      their adopted country. The two examples show that trachoma was a convenient
      excuse to condemn inefficient immigration policy and regulate allegedly diseased
      Asian bodies. In 1910, the federal government made a decision to relegate to
      steamship companies full responsibility for medical inspection at Asian ports.
      Since they had to pay a fine for every immigrant excluded at American borders for
      medical reasons, including trachoma, steamship companies carried out more
      rigorous examinations. With medical advancements and growing interest in
      parasitic diseases, trachoma soon lost its appeal to immigration authorities.
      However, the association of immigration, race, and disease has continued to
      provide a rationale for immigration control beyond American borders. 

PMID- 25608510
TI  - [KJMH's note on a case involving an alleged violation of the KSHM Code of
      Research Ethics].

PMID- 25608511
TI  - Environmental variation and rivers govern the structure of chimpanzee genetic
      diversity in a biodiversity hotspot.
AB  - BACKGROUND: The mechanisms that underlie the diversification of tropical animals
      remain poorly understood, but new approaches that combine geo-spatial modeling
      with spatially explicit genetic data are providing fresh insights on this topic.
      Data about the diversification of tropical mammals remain particularly sparse,
      and vanishingly few opportunities exist to study endangered large mammals that
      increasingly exist only in isolated pockets. The chimpanzees of Cameroon
      represent a unique opportunity to examine the mechanisms that promote genetic
      differentiation in tropical mammals because the region is home to two chimpanzee
      subspecies: Pan troglodytes ellioti and P. t. trogolodytes. Their ranges converge
      in central Cameroon, which is a geographically, climatically and environmentally
      complex region that presents an unparalleled opportunity to examine the roles of
      rivers and/or environmental variation in influencing the evolution of chimpanzee
      populations. RESULTS: We analyzed microsatellite genotypes and mtDNA HVRI
      sequencing data from wild chimpanzees sampled at a fine geographic scale across
      Cameroon and eastern Nigeria using a spatially explicit approach based upon
      Generalized Dissimilarity Modeling. Both the Sanaga River and environmental
      variation were found to contribute to driving separation of the subspecies. The
      importance of environmental variation differed among subspecies. Gene-environment
      associations were weak in P. t. troglodytes, whereas environmental variation was
      found to play a much larger role in shaping patterns of genetic differentiation
      in P. t. ellioti. CONCLUSIONS: We found that both the Sanaga River and
      environmental variation likely play a role in shaping patterns of chimpanzee
      genetic diversity. Future studies using single nucleotide polymorphism (SNP) data
      are necessary to further understand how rivers and environmental variation
      contribute to shaping patterns of genetic variation in chimpanzees.

PMID- 25608513
TI  - Correction.
AB  - [This corrects the article on p. 430 in vol. 7, PMID: 25558305.]. 

PMID- 25608512
TI  - KSR1 is coordinately regulated with Notch signaling and oxidative phosphorylation
      in thyroid cancer.
AB  - Kinase suppressor of RAS1 (KSR1) is a scaffold protein implicated in RAS-mediated
      RAF activation. However, the molecular function of KSR in papillary thyroid
      cancer (PTC) is unknown. Thus, this study aimed to characterize the role of KSR1
      in patients with PTC. qRT-PCR and immunohistochemistry (IHC) revealed inter-tumor
      heterogeneities in the expression of KSR1 in PTC tissues. Interestingly,
      BRAFV600E-positive PTC showed higher KSR1 mRNA expression than BRAFV600E-negative
      PTC (P<0.001). Gene Set Enrichment Analysis (GSEA) using public repositories
      showed that high KSR1 expression coordinately upregulated Notch signaling
      (nominal P=0.019, false discovery rate (FDR) q-value=0.165); this finding was
      supported by GeneNetwork analysis, indicating that KSR1 expression is positively
      correlated with NOTCH1 expression (rho=0.677, P=6.15*10(-9)). siRNA against KSR1
      (siKSR1) significantly decreased ERK phosphorylation induced by BRAFV600E,
      resulting in reduced expression of NOTCH1 and HES1, targets of Notch signaling.
      GSEA revealed that high KSR1 expression was also associated with downregulation
      of genes related to oxidative phosphorylation (OxPhos). Consistent with this,
      electron microscopy showed that PTCs with high KSR1 expression exhibited
      structural defects of the mitochondrial cristae. Furthermore, siKSR1-transfected
      BCPAP and 8505C cells generated fewer colonies in colony-forming assays. In
      addition, GSEA showed that high expression of KSR2 and connector enhancer of KSR1
      (CNKSR1) also coordinately upregulated Notch signaling (KSR2: nominal P=0.0097,
      FDR q-value=0.154 and CNKSR1: nominal P<0.0001, FDR q-value=0.00554), and high
      CNKSR2 was associated with downregulation of the OxPhos gene set (nominal
      P<0.0001, FDR q-value <0.0001). In conclusion, KSR1 is coordinately regulated
      with Notch signaling and OxPhos in PTC, because its scaffold function might be
      required to sustain the proliferative signaling and metabolic remodeling
      associated with this type of cancer.

PMID- 25608514
TI  - At least 80 people have died in Crimea since Russian law banned opioid
      substitutes, says UN special envoy.

PMID- 25608515
TI  - Amphotericin B stimulates gammadelta T and NK cells, and enhances protection from
      Salmonella infection.
AB  - Amphotericin B (AmB) is a commonly used antifungal drug, with well-documented
      effects on cellular immune responses. We determined that AmB-stimulated
      gammadelta T-cell activation and proliferation in vitro at very low
      concentrations. AmB also enhanced IFN-gamma production by NK cells in combination
      with IL-18. AmB had a greater effect on IFN-gamma production in cells isolated
      from very young animals. Although innate immunostimulatory aspects of AmB have
      been defined, AmB has not been extensively applied in non-fungal infection
      settings. Given that gammadelta T cells are increased and activated in Salmonella
      infection in cattle, we assessed the effects of AmB in protection from Salmonella
      enterocolitis in calves. One injection of AmB, at approximately one-tenth of the
      concentration used in human patients to counter fungal infection, or saline
      control, was delivered intravenously to calves prior to infection with
      Salmonella. This single injection caused no adverse effects, reduced disease
      symptoms from Salmonella enterocolitis and significantly reduced Salmonella
      bacteria shed in feces of infected animals. Our findings suggest that AmB may be
      an inexpensive and readily available prophylactic approach for the prevention of
      bacterial infection in calves. 

PMID- 25608516
TI  - Uncovering microbes' role in tumor progression.

PMID- 25608517
TI  - Dipteran wing motor-inspired flapping flight versatility and effectiveness
      enhancement.
AB  - Insects are a prime source of inspiration towards the development of small-scale,
      engineered, flapping wing flight systems. To help interpret the possible energy
      transformation strategies observed in Diptera as inspiration for mechanical
      flapping flight systems, we revisit the perspective of the dipteran wing motor as
      a bistable click mechanism and take a new, and more flexible, outlook to the
      architectural composition previously considered. Using a representative
      structural model alongside biological insights and cues from nonlinear dynamics,
      our analyses and experimental results reveal that a flight mechanism able to
      adjust motor axial support stiffness and compression characteristics may
      dramatically modulate the amplitude range and type of wing stroke dynamics
      achievable. This corresponds to significantly more versatile aerodynamic force
      generation without otherwise changing flapping frequency or driving force
      amplitude. Whether monostable or bistable, the axial stiffness is key to enhance
      compressed motor load bearing ability and aerodynamic efficiency, particularly
      compared with uncompressed linear motors. These findings provide new foundation
      to guide future development of bioinspired, flapping wing mechanisms for micro
      air vehicle applications, and may be used to provide insight to the dipteran
      muscle-to-wing interface. 

PMID- 25608519
TI  - India's private medical colleges and capitation fees.

PMID- 25608518
TI  - Conservation of complete trimethylation of lysine-43 in the rotor ring of c
      subunits of metazoan adenosine triphosphate (ATP) synthases.
AB  - The rotors of ATP synthases turn about 100 times every second. One essential
      component of the rotor is a ring of hydrophobic c-subunits in the membrane domain
      of the enzyme. The rotation of these c-rings is driven by a transmembrane proton
      motive force, and they turn against a surface provided by another membrane
      protein, known as subunit a. Together, the rotating c-ring and the static subunit
      a provide a pathway for protons through the membrane in which the c-ring and
      subunit a are embedded. Vertebrate and invertebrate c-subunits are well
      conserved. In the structure of the bovine F1-ATPase-c-ring subcomplex, the 75
      amino acid c-subunit is folded into two transmembrane alpha-helices linked by a
      short loop. Each bovine rotor-ring consists of eight c-subunits with the N- and C
      terminal alpha-helices forming concentric inner and outer rings, with the loop
      regions exposed to the phospholipid head-group region on the matrix side of the
      inner membrane. Lysine-43 is in the loop region and its epsilon-amino group is
      completely trimethylated. The role of this modification is unknown. If the
      trimethylated lysine-43 plays some important role in the functioning, assembly or
      degradation of the c-ring, it would be expected to persist throughout vertebrates
      and possibly invertebrates also. Therefore, we have carried out a proteomic
      analysis of c-subunits across representative species from different classes of
      vertebrates and from invertebrate phyla. In the twenty-nine metazoan species that
      have been examined, the complete methylation of lysine-43 is conserved, and it is
      likely to be conserved throughout the more than two million extant metazoan
      species. In unicellular eukaryotes and prokaryotes, when the lysine is conserved
      it is unmethylated, and the stoichiometries of c-subunits vary from 9-15. One
      possible role for the trimethylated residue is to provide a site for the specific
      binding of cardiolipin, an essential component of ATP synthases in mitochondria. 

PMID- 25608521
TI  - Walking groups improve cardiovascular and general health, study shows.

PMID- 25608520
TI  - The Effects of Highly Challenging Balance Training in Elderly With Parkinson's
      Disease: A Randomized Controlled Trial.
AB  - BACKGROUND: Highly challenging exercises have been suggested to induce
      neuroplasticity in individuals with Parkinson's disease (PD); however, its effect
      on clinical outcomes remains largely unknown. OBJECTIVE: To evaluate the short
      term effects of the HiBalance program, a highly challenging balance-training
      regimen that incorporates both dual-tasking and PD-specific balance components,
      compared with usual care in elderly with mild to moderate PD. METHODS:
      Participants with PD (n = 100) were randomized, either to the 10-week HiBalance
      program (n = 51) or to the control group (n = 49). Participants were evaluated
      before and after the intervention. The main outcomes were balance performance
      (Mini-BESTest), gait velocity (during normal and dual-task gait), and concerns
      about falling (Falls Efficacy Scale-International). Performance of a cognitive
      task while walking, physical activity level (average steps per day), and
      activities of daily living were secondary outcomes. RESULTS: A total of 91
      participants completed the study. After the intervention, the between group
      comparison showed significantly improved balance and gait performance in the
      training group. Moreover, although no significant between group difference was
      observed regarding gait performance during dual-tasking; the participants in the
      training group improved their performance of the cognitive task while walking, as
      compared with the control group. Regarding physical activity levels and
      activities of daily living, in comparison to the control group, favorable results
      were found for the training group. No group differences were found for concerns
      about falling. CONCLUSIONS: The HiBalance program significantly benefited balance
      and gait abilities when compared with usual care and showed promising transfer
      effects to everyday living. Long-term follow-up assessments will further explore
      these effects.

PMID- 25608522
TI  - Acute gastrointestinal illness following a prolonged community-wide water
      emergency.
AB  - The drinking water infrastructure in the United States is ageing; extreme weather
      events place additional stress on water systems that can lead to interruptions in
      the delivery of safe drinking water. We investigated the association between
      household exposures to water service problems and acute gastrointestinal illness
      (AGI) and acute respiratory illness (ARI) in Alabama communities that experienced
      a freeze-related community-wide water emergency. Following the water emergency,
      investigators conducted a household survey. Logistic regression models were used
      to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI)
      for self-reported AGI and ARI by water exposures. AGI was higher in households
      that lost water service for ?7 days (aPR 2.4, 95% CI 1.1-5.2) and experienced low
      water pressure for ?7 days (aPR 3.6, 95% CI 1.4-9.0) compared to households that
      experienced normal service and pressure; prevalence of AGI increased with
      increasing duration of water service interruptions. Investments in the ageing
      drinking water infrastructure are needed to prevent future low-pressure events
      and to maintain uninterrupted access to the fundamental public health protection
      provided by safe water supplies. Households and communities need to increase
      their awareness of and preparedness for water emergencies to mitigate adverse
      health impacts. 

PMID- 25608523
TI  - Effects of Antenatal Corticosteroids on Cortisol and Heart Rate Reactivity of
      Preterm Infants.
AB  - Administration of glucocorticoids (GCs) during pregnancy is an established
      practice for reducing morbidity and mortality of fetuses at risk of preterm
      delivery. However, preliminary research indicates that exposure to exogenous GCs
      in utero may be associated with suppressed hypothalamic-pituitary-adrenal axis
      activity. The aim of this study was to determine whether preterm neonates who are
      exposed to antenatal corticosteroids show evidence of a suppressed stress
      response system during their first few weeks of life, in contrast to infants who
      are not exposed. The sample (51% female) included 57 neonates, with 74% exposed
      to steroids. Mean gestational ages (GAs) were 32.6 weeks for exposed and 34.7
      weeks for nonexposed infants. Although neonates in the two groups differed in
      gender, birth weight, and morbidity, these factors were controlled for in data
      analyses. Infants' salivary cortisol and heart rate (HR) were measured before and
      after they received a standardized caregiving "stressor" while in the newborn
      intensive care unit. Infants exposed to GCs in utero had lower basal cortisol
      levels and higher HRs than their nonexposed peers. In contrast to infants who
      received no GCs, they also exhibited minimal HR or cortisol reactivity to the
      stressor. Findings suggest that preterm infants who were exposed to antenatal
      corticosteroids experience a suppressed response to stress. As preterm children
      develop, this dysregulation has numerous implications for later development of
      stress-related cardiovascular and mental health problems. Further research is
      needed to determine whether these postnatal effects of antenatal corticosteroids
      persist over time. 

PMID- 25608524
TI  - Exploring how the tobacco industry presents and promotes itself in social media.
AB  - BACKGROUND: The commercial potential of social media is utilized by tobacco
      manufacturers and vendors for tobacco promotion online. However, the prevalence
      and promotional strategies of pro-tobacco content in social media are still not
      widely understood. OBJECTIVE: The goal of this study was to reveal what is
      presented by the tobacco industry, and how it promotes itself, on social media
      sites. METHODS: The top 70 popular cigarette brands are divided into two groups
      according to their retail prices: group H (brands with high retail prices) and
      group L (brands with low retail prices). Three comprehensive searches were
      conducted on Facebook, Wikipedia, and YouTube respectively using the top 70
      popular cigarette brands as keywords. We identified tobacco-related content
      including history and culture, product features, health warnings, home page of
      cigarette brands, and Web-based tobacco shops. Furthermore, we examined the
      promotional strategies utilized in social media. RESULTS: According to the data
      collected from March 3, 2014 to March 10, 2014, 43 of the 70 representative
      cigarette brands had created 238 Facebook fan pages, 46 cigarette brands were
      identified in Wikipedia, and there were over 120,000 pro-tobacco videos on
      YouTube, associated with 61 cigarette brands. The main content presented on the
      three social media websites differs significantly. Wikipedia focuses on history
      and culture (67%, 32/48; P<.001). Facebook mainly covers history and culture
      (37%, 16/43; P<.001) and major products (35%, 15/43), while YouTube focuses on
      the features of major tobacco products (79%, 48/61; P=.04) and information about
      Web-based shops (49%, 30/61; P=.004). Concerning the content presented by groups
      H and L, there is no significant difference between the two groups. With regard
      to the promotional strategies used, sales promotions exist extensively in social
      media. Sales promotion is more prevalent on YouTube than on the other two sites
      (64%, 39/61 vs 35%, 15/43; P=.004). Generally, the sale promotions of higher-cost
      brands in social media are more prevalent than those of lower-cost brands (55%,
      16/29 vs 7%, 1/14; P<.001 for Facebook; 78%, 28/36 vs 44%, 11/25; P=.005 for
      YouTube). CONCLUSIONS: The prevalence of cigarette brands in social media allows
      more pro-tobacco information to be accessed by online users. This dilemma
      indicates that corresponding regulations should be established to prevent tobacco
      promotion in social media.

PMID- 25608525
TI  - Tim-3 fosters HCC development by enhancing TGF-beta-mediated alternative
      activation of macrophages.
AB  - OBJECTIVE: Tumour-associated macrophages (TAMs) and their alternative activation
      contribute greatly to the development of hepatocellular carcinoma (HCC). Tim-3 is
      highly expressed on macrophages and regulates macrophage functions in several
      conditions. However, whether Tim-3 is involved in the activation and the function
      of TAMs has not been reported. DESIGN: Tim-3 expression in HCC samples was
      evaluated by flow cytometry, immunohistochemistry and confocal analysis. We
      analysed the effects of Tim-3 knockdown on macrophages in growth of H22 tumour
      homografts in BALB/c mice. Tim-3 interference was performed by neutralising
      antibody, small interfering RNA or short hairpin RNA-expressing lentivirus.
      Cytokine production was evaluated by reverse transcription PCR, ELISA or
      Cytometric Bead Array. The effects of Tim-3 interference in macrophages were
      examined with regard to alternative activation of macrophages and proliferation
      and migration of Hepa1-6 cells. Cell growth curve, colony formation and transwell
      assays were involved to estimate cell proliferation and migration. RESULTS: Tim-3
      expression was significantly increased in both peripheral blood monocytes and
      TAMs in patients with HCC. The Tim-3 expression in monocytes/TAMs strongly
      correlated with higher tumour grades and the poor survival of patients with HCC.
      Consistently, HCC conditioned medium or transforming growth factor-beta fostered
      Tim-3 expression and the alternative activation of macrophages. Moreover, Tim-3
      interference in macrophages significantly inhibited the alternative activation of
      macrophages and suppressed HCC cell growth both in vitro and in vivo. Blocking
      interleukin 6 reversed the Tim-3-mediated effects on HCC cell growth in vitro.
      CONCLUSIONS: Tim-3 displays critical roles in microenvironment-induced activation
      and protumoral effects of TAMs in HCC. Interference of Tim-3 might be great
      potential in HCC therapy.

PMID- 25608526
TI  - Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum
      stress.
AB  - BACKGROUND: Methyl donor deficiency (MDD) aggravates experimental colitis in rats
      and increases endoplasmic reticulum (ER) stress through decreased sirtuin 1
      (SIRT1) in neuronal cells and myocardium. ER stress plays a key role in IBD
      pathogenesis. AIM: We investigated whether the influence of MDD on colitis
      resulted from an ER stress response triggered by decreased SIRT1 expression.
      DESIGN: The unfolded protein response (UPR), chaperones proteins, heat shock
      factor protein 1 (HSF1) and SIRT1 were examined in rats with MDD and dextran
      sulfate sodium (DSS)-induced colitis in a Caco-2 cell model with stable
      expression of transcobalamin-oleosin (TO) chimera, which impairs cellular
      availability of vitamin B12, and in IBD. The effects of SIRT1 activation were
      studied both in vitro and in vivo. RESULTS: MDD aggravated DSS-induced colitis
      clinically, endoscopically and histologically. MDD activated ER stress pathways,
      with increased phosphorylate-PKR-like ER kinase, P-eiF-2alpha, P-IRE-1alpha,
      activating transcription factor (ATF)6, XBP1-S protein and ATF4 mRNA expression
      levels in rats. This was accompanied by reduced SIRT1 expression level and
      greater acetylation of HSF1, in relation with a dramatic decrease of chaperones
      (binding immunoglobulin protein (BIP), heat shock protein (HSP)27 and HSP90).
      Adding either vitamin B12, S-adenosylmethionine or an SIRT1 activator (SRT1720)
      reduced the UPR in vitro. In rats, SIRT1 activation by SRT1720 prevented colitis
      by reducing HSF1 acetylation and increasing expression of BIP, HSP27 and HSP90.
      Immunohistochemistry showed impaired expression of SIRT1 in the colonic
      epithelium of patients with IBD. CONCLUSIONS: SIRT1 is a master regulator of ER
      stress and severity of experimental colitis in case of MDD. It could deserve
      further interest as a therapeutic target of IBD.

PMID- 25608527
TI  - Fibroblast inward-rectifier potassium current upregulation in profibrillatory
      atrial remodeling.
AB  - RATIONALE: Fibroblasts are involved in cardiac arrhythmogenesis and contribute to
      the atrial fibrillation substrate in congestive heart failure (CHF) by generating
      tissue fibrosis. Fibroblasts display robust ion currents, but their functional
      importance is poorly understood. OBJECTIVE: To characterize atrial fibroblast
      inward-rectifier K(+) current (IK1) remodeling in CHF and its effects on
      fibroblast properties. METHODS AND RESULTS: Freshly isolated left atrial
      fibroblasts were obtained from controls and dogs with CHF (ventricular
      tachypacing). Patch clamp was used to record resting membrane potential (RMP) and
      IK1. RMP was significantly increased by CHF (from -43.2+/-0.8 mV, control, to 
      55.5+/-0.9 mV). CHF upregulated IK1 (eg, at -90 mV from -1.1+/-0.2 to -2.7+/-0.5
      pA/pF) and increased the expression of KCNJ2 mRNA (by 52%) and protein (by 80%).
      Ba(2+) (300 MUmol/L) decreased the RMP and suppressed the RMP difference between
      controls and dogs with CHF. Store-operated Ca(2+) entry (Fura-2-acetoxymethyl
      ester) and fibroblast proliferation (flow cytometry) were enhanced by CHF.
      Lentivirus-mediated overexpression of KCNJ2 enhanced IK1 and hyperpolarized
      fibroblasts. Functional KCNJ2 suppression by lentivirus-mediated expression of a
      dominant negative KCNJ2 construct suppressed IK1 and depolarized RMP.
      Overexpression of KCNJ2 increased Ca(2+) entry and fibroblast proliferation,
      whereas the dominant negative KCNJ2 construct had opposite effects. Fibroblast
      hyperpolarization to mimic CHF effects on RMP enhanced the Ca(2+) entry. MicroRNA
      26a, which targets KCNJ2, was downregulated in CHF fibroblasts. Knockdown of
      endogenous microRNA-26 to mimic CHF effects unregulated IK1. CONCLUSIONS: CHF
      upregulates fibroblast KCNJ2 expression and currents, thereby hyperpolarizing
      RMP, increasing Ca(2+) entry, and enhancing atrial fibroblast proliferation.
      These effects are likely mediated by microRNA-26a downregulation. Remodeling
      induced fibroblast KCNJ2 expression changes may play a role in atrial
      fibrillation promoting fibroblast remodeling and structural/arrhythmic
      consequences.

PMID- 25608528
TI  - Role of cAMP-phosphodiesterase 1C signaling in regulating growth factor receptor
      stability, vascular smooth muscle cell growth, migration, and neointimal
      hyperplasia.
AB  - RATIONALE: Neointimal hyperplasia characterized by abnormal accumulation of
      vascular smooth muscle cells (SMCs) is a hallmark of occlusive disorders such as
      atherosclerosis, postangioplasty restenosis, vein graft stenosis, and allograft
      vasculopathy. Cyclic nucleotides are vital in SMC proliferation and migration,
      which are regulated by cyclic nucleotide phosphodiesterases (PDEs). OBJECTIVE:
      Our goal is to understand the regulation and function of PDEs in SMC pathogenesis
      of vascular diseases. METHODS AND RESULTS: We performed screening for genes
      differentially expressed in normal contractile versus proliferating synthetic
      SMCs. We observed that PDE1C expression was low in contractile SMCs but
      drastically elevated in synthetic SMCs in vitro and in various mouse vascular
      injury models in vivo. In addition, PDE1C was highly induced in neointimal SMCs
      of human coronary arteries. More importantly, injury-induced neointimal formation
      was significantly attenuated by PDE1C deficiency or PDE1 inhibition in vivo. PDE1
      inhibition suppressed vascular remodeling of human saphenous vein explants ex
      vivo. In cultured SMCs, PDE1C deficiency or PDE1 inhibition attenuated SMC
      proliferation and migration. Mechanistic studies revealed that PDE1C plays a
      critical role in regulating the stability of growth factor receptors, such as
      PDGF receptor beta (PDGFRbeta) known to be important in pathological vascular
      remodeling. PDE1C interacts with low-density lipoprotein receptor-related protein
      1 and PDGFRbeta, thus regulating PDGFRbeta endocytosis and lysosome-dependent
      degradation in an low-density lipoprotein receptor-related protein-1-dependent
      manner. A transmembrane adenylyl cyclase cAMP-dependent protein kinase cascade
      modulated by PDE1C is critical in regulating PDGFRbeta degradation. CONCLUSIONS:
      These findings demonstrated that PDE1C is an important regulator of SMC
      proliferation, migration, and neointimal hyperplasia, in part through modulating
      endosome/lysosome-dependent PDGFRbeta protein degradation via low-density
      lipoprotein receptor-related protein-1.

PMID- 25608529
TI  - IP3 signalling regulates exogenous RNAi in Caenorhabditis elegans.
AB  - RNA interference (RNAi) is a widespread and widely exploited phenomenon. Here, we
      show that changing inositol 1,4,5-trisphosphate (IP3) signalling alters RNAi
      sensitivity in Caenorhabditis elegans. Reducing IP3 signalling enhances
      sensitivity to RNAi in a broad range of genes and tissues. Conversely up
      regulating IP3 signalling decreases sensitivity. Tissue-specific rescue
      experiments suggest IP3 functions in the intestine. We also exploit IP3
      signalling mutants to further enhance the sensitivity of RNAi hypersensitive
      strains. These results demonstrate that conserved cell signalling pathways can
      modify RNAi responses, implying that RNAi responses may be influenced by an
      animal's physiology or environment. 

PMID- 25608531
TI  - Microtrack migration: insights into 3D cell motility. Focus on "Comparative
      mechanisms of cancer cell migration through 3D matrix and physiological
      microtracks".

PMID- 25608530
TI  - Plasticity of PI4KIIIalpha interactions at the plasma membrane.
AB  - Plasma membrane PI4P is an important direct regulator of many processes that
      occur at the plasma membrane and also a biosynthetic precursor of PI(4,5)P2 and
      its downstream metabolites. The majority of this PI4P pool is synthesized by an
      evolutionarily conserved complex, which has as its core the PI 4-kinase
      PI4KIIIalpha (Stt4 in yeast) and also comprises TTC7 (Ypp1 in yeast) and the
      peripheral plasma membrane protein EFR3. While EFR3 has been implicated in the
      recruitment of PI4KIIIalpha via TTC7, the plasma membrane protein Sfk1 was also
      shown to participate in this targeting and activity in yeast. Here, we identify a
      member of the TMEM150 family as a functional homologue of Sfk1 in mammalian cells
      and demonstrate a role for this protein in the homeostatic regulation of
      PI(4,5)P2 at the plasma membrane. We also show that the presence of TMEM150A
      strongly reduces the association of TTC7 with the EFR3-PI4KIIIalpha complex,
      without impairing the localization of PI4KIIIalpha at the plasma membrane.
      Collectively our results suggest a plasticity of the molecular interactions that
      control PI4KIIIalpha localization and function. 

PMID- 25608533
TI  - Myotubes from lean and severely obese subjects with and without type 2 diabetes
      respond differently to an in vitro model of exercise.
AB  - Exercise improves insulin sensitivity and oxidative capacity in skeletal muscles.
      However, the effect of exercise on substrate oxidation is less clear in obese and
      type 2 diabetic subjects than in lean subjects. We investigated glucose and lipid
      metabolism and gene expression after 48 h with low-frequency electrical pulse
      stimulation (EPS), as an in vitro model of exercise, in cultured myotubes
      established from lean nondiabetic subjects and severely obese subjects (BMI >= 40
      kg/m(2)) with and without type 2 diabetes. EPS induced an increase in insulin
      sensitivity but did not improve lipid oxidation in myotubes from severely obese
      subjects. Thus, EPS-induced increases in insulin sensitivity and lipid oxidation
      were positively and negatively correlated to BMI of the subjects, respectively.
      EPS enhanced oxidative capacity of glucose in myotubes from all subjects.
      Furthermore, EPS reduced mRNA expression of slow fiber-type marker (MYH7) in
      myotubes from diabetic subjects; however, the protein expression of this marker
      was not significantly affected by EPS in either of the donor groups. On the
      contrary, mRNA levels of interleukin-6 (IL-6) and IL-8 were unaffected by EPS in
      myotubes from diabetic subjects, while IL-6 mRNA expression was increased in
      myotubes from nondiabetic subjects. EPS-stimulated mRNA expression levels of
      MYH7, IL-6, and IL-8 correlated negatively with subjects' HbA1c and/or fasting
      plasma glucose, suggesting an effect linked to the diabetic phenotype. Taken
      together, these data show that myotubes from different donor groups respond
      differently to EPS, suggesting that this effect may reflect the in vivo
      characteristics of the donor groups.

PMID- 25608534
TI  - Unusual endoscopic presentation of eosinophilic gastroenteropathy.

PMID- 25608532
TI  - Identification of Tyr residues that enhance folate substrate binding and
      constrain oscillation of the proton-coupled folate transporter (PCFT-SLC46A1).
AB  - The proton-coupled folate transporter (PCFT) mediates intestinal folate
      absorption and transport of folates across the choroid plexus. This study focuses
      on the role of Tyr residues in PCFT function. The substituted Cys-accessibility
      method identified four Tyr residues (Y291, Y362, Y315, and Y414) that are
      accessible to the extracellular compartment; three of these (Y291, Y362, and
      Y315) are located within or near the folate binding pocket. When the Tyr residues
      were replaced with Cys or Ala, these mutants showed similar (up to 6-fold)
      increases in influx Vmax and Kt/Ki for [(3)H]methotrexate and [(3)H]pemetrexed.
      When the Tyr residues were replaced with Phe, these changes were moderated or
      absent. When Y315A PCFT was used as representative of the mutants and
      [(3)H]pemetrexed as the transport substrate, this substitution did not increase
      the efflux rate constant. Furthermore, neither influx nor efflux mediated by
      Y315A PCFT was transstimulated by the presence of substrate in the opposite
      compartment; however, substantial bidirectional transstimulation of transport was
      mediated by wild-type PCFT. This resulted in a threefold greater efflux rate
      constant for cells that express wild-type PCFT than for cells that express Y315
      PCFT under exchange conditions. These data suggest that these Tyr residues,
      possibly through their rigid side chains, secure the carrier in a high-affinity
      state for its folate substrates. However, this may be achieved at the expense of
      constraining the carrier's mobility, thereby decreasing the rate at which the
      protein oscillates between its conformational states. The Vmax generated by these
      Tyr mutants may be so rapid that further augmentation during transstimulation may
      not be possible.

PMID- 25608535
TI  - Impact of high-resolution manometry on achalasia diagnosis and treatment.
AB  - Achalasia is a primary neurodegenerative disorder of the esophagus characterized
      by loss of function of the lower esophageal sphincter (LES) and of esophageal
      peristalsis, which causes symptoms such as dysphagia, regurgitation, weight loss,
      and chest pain. Esophageal manometry is the gold standard for the diagnosis of
      achalasia. The typical manometric features are incomplete relaxation of a
      frequently hypertensive LES and lack of peristalsis in the tubular esophagus.
      High-resolution manometry using catheters with 36 solid-state sensors spaced 1cm
      apart has more and more replaced water-perfused and pull-through manometry.
      However, the main innovation of this method is the conversion of pressure data
      into a topographical plot. The data can be modified using interpolation to
      generate high-resolution esophageal pressure topography (HREPT). HREPT is more
      sensitive, provides more detailed information, and is easier to perform than
      conventional manometry. Introduction of HREPT had an impact especially on the
      diagnosis and management of achalasia. A clinically relevant impact was achieved
      by the identification of 3 clinical subtypes which seem to predict treatment
      outcomes. This review analyzes the progress made in the diagnosis and management
      of achalasia since the recent introduction of HREPT.

PMID- 25608536
TI  - Wearable sensors in syncope management.
AB  - Syncope is a common disorder with a lifetime prevalence of about 40%. Implantable
      cardiac electronic devices, including implantable loop recorders (ILR) and
      implantable cardioverter-defibrillators (ICD), are well established in syncope
      management. However, despite the successful use of ILR and ICD, diagnosis and
      therapy still remain challenging in many patients due to the complex hemodynamic
      interplay of cardiac and vascular adaptations during impending syncopes. Wearable
      sensors might overcome some limitations, including misdiagnosis and inappropriate
      defibrillator shocks, because a variety of physiological measures can now be
      easily acquired by a single non-invasive device at high signal quality. In
      neurally-mediated syncope (NMS), which is the most common cause of syncope,
      advanced signal processing methodologies paved the way to develop devices for
      early syncope detection. In contrast to the relatively benign NMS, in arrhythmia
      related syncopes immediate therapeutical intervention, predominantly by
      electrical defibrillation, is often mandatory. However, in patients with a
      transient risk of arrhythmia-related syncope, limitations of ICD therapy might
      outweigh their potential therapeutic benefits. In this context the wearable
      cardioverter-defibrillator offers alternative therapeutical options for some high
      risk patients. Herein, we review recent evidence demonstrating that wearable
      sensors might be useful to overcome some limitations of implantable devices in
      syncope management.

PMID- 25608537
TI  - Long-term survival after endoscopic resection for early gastric cancer in the
      remnant stomach: comparison with radical surgery.

PMID- 25608538
TI  - [Predictive validity of the Braden Scale for pressure ulcer risk: a meta
      analysis].
AB  - PURPOSE: The Braden Scale is one of the most intensively studied risk assessment
      scales used in identifying the risk of developing pressure sore. However, not all
      studies show that the predictive validity of this scale is sufficient. The
      purpose of this study was to evaluate the Braden Scale for predicting pressure
      ulcer development. METHODS: Articles published 1946 and 2013 from periodicals
      indexed in Ovid Medline, Embase, CINAHL, KoreaMed, NDSL and other databases were
      selected, using the following keywords: 'pressure ulcer'. The QUADAS-II was
      applied to assess the internal validity of the diagnostic studies. Selected
      studies were analyzed using meta-analysis with MetaDisc 1.4. RESULTS: Thirty
      eight diagnostic studies with high methodological quality, involving 17,934
      patients, were included. Results of the meta-analysis showed that the pooled
      sensitivity and specificity of the Braden Scale were 0.74 (95% CI: 0.72-0.76),
      0.75 (95% CI: 0.74-0.76) respectively. However the predictive validity of the
      Braden Scale has limitation because there was high heterogeneity between studies.
      CONCLUSION: The Braden Scale's predictive validity of risk for pressure ulcer is
      interpreted as at a moderate level. However there is a limitation to the
      interpretation of the results, because of high heterogeneity among the studies.

PMID- 25608539
TI  - [Influence of self efficacy, social support and sense of community on health
      related quality of life for middle-aged and elderly residents living in a rural
      community].
AB  - PURPOSE: The purpose of this study was to examine the relationship between self
      efficacy, social support, sense of community and health-related quality of life
      (HRQoL), including the direct and indirect effects of the variables on HRQoL.
      METHODS: A cross-sectional survey was conducted with a convenience sample of 249
      middle-aged and elderly residents living in a rural community in A-County, K
      Province. The structured questionnaire included 4 scales from the Euro Quality of
      life-5 Dimensions (mobility, self-care, usual activities, pain/discomfort,
      anxiety/depression), and measures of General Self-Efficacy, Social Support, and
      Sense of Community. Data were analyzed using SPSS WIN 20.0 and AMOS 21.0 program.
      RESULTS: The mean HRQoL score for the participants was 0.87+/-0.13. Self-efficacy
      (beta=.13, p=.039) and age (beta= -.38, p<.001) were significantly associated
      with HRQoL, explaining 21% of the variance. In the path analysis, self-efficacy
      showed a significant direct effect on HRQoL (beta=.14, p=.040) and significantly
      mediating relationships between both social support (beta=.05, p=.030) and sense
      of community (beta=.02, p=.025) and HRQoL. CONCLUSION: Although self-efficacy was
      found to be the main predictor for HRQoL, the findings imply that social
      environmental factors such as social support and sense of community need to be
      considered when developing interventions to increase HRQoL in middle-aged and
      elderly residents in rural communities.

PMID- 25608540
TI  - [Maternal conflicts of Vietnamese married immigrant women in Korea].
AB  - PURPOSE: The purpose of the study was to identify and explain the essences and
      structures of maternal conflicts in Vietnamese married immigrant women in Korea.
      METHODS: A phenomenological methodology was used for the study. Eleven Vietnamese
      married immigrant women participated in the study. Verbatim transcripts were
      analyzed using Colaizzi's method. RESULTS: Four categories, 10 clusters and 26
      themes emerged from the data for the experience in maternal conflicts of
      Vietnamese married immigrant women. The four categories were 'An unprepared young
      motherhood in another culture', 'Feeling left out of the mother's place along the
      bands of Nap tai tradition', 'My image is like not-being able to stand alone/be
      independent' and 'Finding hope in motherhood despite of conflicts and stigmas'.
      CONCLUSION: Vietnamese married immigrant women experienced not only the negative
      aspects but also sublimation of maternal conflicts. Based on the results, health
      professionals need to develop effective nursing interventions toward a positive
      maternal identity and approach with interculturalism for the Vietnamese married
      immigrant women in Korea.

PMID- 25608541
TI  - [Development of a stress scale for elderly patients with coronary artery
      disease].
AB  - PURPOSE: The purpose of this study was to develop a scale to evaluate stress in
      elderly patients with coronary artery diseases (CAD) and to examine validity and
      reliability of the scale. METHODS: The development process for the preliminary
      scale included construction of a conceptual framework and initial items,
      verification of content analysis, sentence correction, and pilot study. This
      study was conducted using a questionnaire survey with one-to-one interviews
      during January and February, 2012. Participants were 240 elderly patients with
      CAD. Data were analyzed using item analysis, factor analysis, criterion related
      validity, and internal consistency. RESULTS: The developed scale consisted of 32
      items and 6 factors - aging and disease (7 items), family relations (5 items),
      anxiety and withdrawal (9 items), management of daily living (3 items),
      compliance of medical regimen (4 items), poverty and finance (4 items), and
      explained 68.5% of total variance. The scale had significantly positive
      correlation with the Korean Perceived Stress Scale (KPSS). Cronbach's alpha was
      .96, and Guttman split half coefficient was .91. CONCLUSION: Results indicate
      that the Stress Scale for Elderly Patients with CAD has validity and reliability,
      and is a suitable scale in health care settings to assess stress in elderly
      patients with CAD.

PMID- 25608542
TI  - [Life experiences of Korean patients with Hansen's disease in Sorok Island
      Hospital].
AB  - PURPOSE: The purpose of this study was to identify life experiences of Korean
      patients with Hansen's disease (leprosy). METHODS: For this study, 5 participants
      from Sorok Island Hospital were purposively chosen. Data were collected through
      in-depth individual interviews from June to July 2014. Data analysis method was
      based on Colaizzi's approach. RESULTS: The study results showed that experiences
      of patients with Hansen's disease consisted of 14 themes and six theme clusters:
      1) Bad disease approaching as fate; 2) Family breakup and far from the village;
      3) New life in Sorok Island Hospital; 4) Treatment of Hansen's disease and
      disability; 5) Life in the disease community; 6) Comfort and hope of life.
      CONCLUSION: The findings of this study indicate that health care professionals
      should pay attention to patients with Hansen's disease not only to reduce their
      physical and psychological suffering, but also to help the community and public
      culture to reduce the social stigma surrounding this disease and causing
      suffering for the patients. The results of the present study can help us to have
      a better understanding of various aspects of patients' lived experiences.

PMID- 25608543
TI  - [Effect of school-based peer leader centered smoking prevention program].
AB  - PURPOSE: The purpose of this study was to develop and evaluate a school-based
      peer leader centered smoking prevention program. METHODS: Non-equivalent control
      group with a pre/post-test design was used. Students (n=174) in two boys' junior
      high schools located in D city, Korea participated with 85 being selected for the
      experimental group and 89 for the control group. Five sessions were given to the
      experimental group and a 50 minute lecture to the control group. Knowledge,
      attitude, non-smoking intention, and non-smoking efficacy were measured for the
      both experimental and control group at two weeks before the program and one month
      after the program was completed. Data were analyzed using chi2-test, Fisher's
      exact test, independent t-test and paired t-test with the SPSS 21.0 program.
      RESULTS: The experimental group showed higher overall knowledge, negative
      attitude toward smoking, and higher non-smoking intention and efficacy. After
      receiving the school based peer leader centered smoking prevention program scores
      for attitude toward smoking and non-smoking efficacy increased in the
      experimental group were higher than in the control group. CONCLUSION: The school
      based peer leader centered smoking prevention program needs longitudinal
      evaluation, but from this study, there is an indication that this program can be
      used with junior high school students and effectively change students' attitude
      toward smoking and promote non-smoking efficacy.

PMID- 25608544
TI  - [A structural equation modeling on premenstrual syndrome in adolescent girls].
AB  - PURPOSE: The aims of this study were to construct a hypothetical structural model
      which explains the premenstrual syndrome (PMS) in adolescent girls and to test
      the fitness with collected data. METHODS: The participants were 1,087 adolescent
      girls from 3 high schools and 5 middle schools in B city. Data were collected
      from July 3 to October 15, 2012 using self-reported questionnaires and were
      analyzed using PASW 18.0 and AMOS 16.0 programs. RESULTS: The overall fitness
      indices of hypothetical model were good (chi2 =1555, p<.001), chi2/df=4.40,
      SRMR=.04, GFI=.91, RMSEA=.05, NFI=.90, TLI=.91, CFI=.92, AIC=1717). Out of 16
      paths, 12 were statistically significant. Daily hassles had the greatest impact
      on PMS in the adolescent girls in this model. In addition, PMS in adolescent
      girls was directly affected by menarche age, Body Mass Index (BMI), amount of
      menstruation, test anxiety, social support, menstrual attitude and femininity but
      not by academic stress. This model explained 27% of the variance in PMS in
      adolescent girls. CONCLUSION: The findings from this study suggest that nursing
      interventions to reduce PMS in adolescent girls should address their daily
      hassles, test anxiety, menstrual attitude and BMI. Also, social support from
      their parents, friends, and teachers needs to be increased.

PMID- 25608545
TI  - [Effects of a coaching program on comprehensive lifestyle modification for women
      with gestational diabetes mellitus].
AB  - PURPOSE: The purpose of this study was to investigate the effects of using a
      Coaching Program on Comprehensive Lifestyle Modification with pregnant women who
      have gestational diabetes. METHODS: The research design for this study was a non
      equivalent control group quasi-experimental study. Pregnant women with
      gestational diabetes were recruited from D women's hospital located in Gyeonggi
      Province from April to October, 2013. Participants in this study were 34 for the
      control group and 34 for the experimental group. The experimental group
      participated in the Coaching Program on Comprehensive Lifestyle Modification. The
      program consisted of education, small group coaching and telephone coaching over
      4weeks. Statistical analysis was performed using the SPSS 21.0 program. RESULTS:
      There were significant improvements in self-care behavior, and decreases in
      depression, fasting blood sugar and HbA1C in the experimental group compared to
      the control group. However, no significant differences were found between the two
      groups for knowledge of gestational diabetes mellitus. CONCLUSION: The Coaching
      Program on Comprehensive Lifestyle Modification used in this study was found to
      be effective in improving self-care behavior and reducing depression, fasting
      blood sugar and HbA1C, and is recommended for use in clinical practice as an
      effective nursing intervention for pregnant women with gestational diabetes.

PMID- 25608546
TI  - [Development and effects of emotional intelligence program for undergraduate
      nursing students: mixed methods research].
AB  - PURPOSE: This study was conducted to develop and test the effects of an emotional
      intelligence program for undergraduate nursing students. METHODS: The study
      design was a mixed method research. Participants were 36 nursing students
      (intervention group: 17, control group: 19). The emotional intelligence program
      was provided for 4 weeks (8 sessions, 20 hours). Data were collected between
      August 6 and October 4, 2013. Quantitative data were analyzed using Chi-square,
      Fisher's exact test, t-test, repeated measure ANOVA, and paired t-test with
      SPSS/WIN 18.0. Qualitative data were analyzed using content analysis. RESULTS:
      Quantitative results showed that emotional intelligence, communication skills,
      resilience, stress coping strategy, and clinical competence were significantly
      better in the experimental group compared to the control group. According to the
      qualitative results, the nursing students experienced improvement in emotional
      intelligence, interpersonal relationships, and empowerment, as well as a
      reduction in clinical practice stress after participation in the emotional
      intelligence program. CONCLUSION: Study findings indicate that the emotional
      intelligence program for undergraduate nursing students is effective and can be
      recommended as an intervention for improving the clinical competence of
      undergraduate students in a nursing curriculum.

PMID- 25608547
TI  - [Effects of community-based comprehensive fall prevention program on muscle
      strength, postural balance and fall efficacy in elderly people].
AB  - PURPOSE: The purposes of this study was to develop a comprehensive community
      based fall prevention program and to test the effects of the program on the
      muscle strength, postural balance and fall efficacy for elderly people. METHODS:
      The design of this study was a nonequivalent control group pretest-posttest
      design. There were 28 participants in the experimental group and 29 in the
      control group. The program consisted of balance exercises, elastic resistance
      exercises and prevention education. The program was provided five times a week
      for 8 weeks and each session lasted 90 minutes. Data were analyzed using chi2
      test, independent t-test and paired t-test using the SPSS program. RESULTS:
      Muscle strength of the lower extremities, postural balance and fall efficacy
      scores significantly improved in the experimental group compared to the control
      group. CONCLUSION: These results suggest that this program can improve lower
      extremity muscle strength, postural balance and fall efficacy in elders.
      Therefore, this program is recommended for use in fall prevention programs for
      elders living in the community.

PMID- 25608548
TI  - [Nutritional status and risk factors for malnutrition in low-income urban
      elders].
AB  - PURPOSE: The purpose of this study was to evaluate the nutritional status of low
      income urban elders by diversified ways, and to analyze the risk factors for
      malnutrition. METHODS: The participants in this study were 183 low-income elders
      registered at a visiting healthcare facility in a public health center. Data were
      collected using anthropometric measurements, and a questionnaire survey. For data
      analysis, descriptive statistics, chi2-test, t-test, Fisher's exact test,
      multiple logistic regression analysis were performed using SPSS 20.0. RESULTS:
      Regarding the nutritional status of low-income elders as measured by the Mini
      Nutritional Assessment (MNA), 10.4% of the elders were classified as
      malnourished; 57.4% as at high risk for malnutrition; and 32.2% as having normal
      nutrition levels. The main factors affecting malnutrition for low-income elders
      were loss of appetite (OR=3.34, 95% CI: 1.16~9.56) and difficulties in meal
      preparation (OR=2.35, 95% CI: 1.13~4.88). CONCLUSION: In order to effectively
      improve nutrition in low-income urban elders, it is necessary to develop
      individual intervention strategies to manage factors that increase the risk of
      malnutrition and to use systematic approach strategies in local communities in
      terms of a nutrition support system.

PMID- 25608549
TI  - [Effectiveness of the Military Mental Health Promotion Program].
AB  - PURPOSE: This study was done to evaluate the Military Mental Health Promotion
      Program. The program was an email based cognitive behavioral intervention.
      METHODS: The research design was a quasi-experimental study with a non-equivalent
      control group pretest-posttest design. Participants were 32 soldiers who agreed
      to participate in the program. Data were collected at three different times from
      January 2012 to March 2012; pre-test, post-test, and a one-month follow-up test.
      The data were statistically analyzed using SPSS 18.0. The effectiveness of the
      program was tested by repeated measures ANOVA. RESULTS: The first hypothesis that
      the level of depression in the experimental group who participated in the program
      would decrease compared to the control group was not supported in that the
      difference in group-time interaction was not statistically significant (F=2.19,
      p=.121). The second and third hypothesis related to anxiety and self-esteem were
      supported in group-time interaction, respectively (F=7.41, p=.001, F=11.67,
      p<.001). CONCLUSION: Results indicate that the program is effective in improving
      soldiers' mental health status in areas of anxiety and self-esteem.

PMID- 25608550
TI  - [Spiritual and psychosocial effects of the spirituality promotion program on
      clinical nurses].
AB  - PURPOSE: The purpose of this study was to evaluate the effects of the
      Spirituality Promotion Program(SPP) for young nurses working in the stressful
      university hospital environment. METHODS: The study included 41 nurses in the
      experimental group, nurses who had worked less than 5 years and completed 8 weeks
      of SPP between June and July in 2011. The control group, 44 nurses, also received
      the same program after the study was completed. For the study, a survey was
      conducted of all participants concerning spirituality, perceived stress, positive
      and negative affect, empathy, job satisfaction, and leadership practice. RESULTS:
      No significant difference was found between the two groups on study variables.
      Perceived stress decreased significantly in the experimental group (p=.012).
      Spirituality (p=.019), positive affect (p=.014), empathy (p=.004), job
      satisfaction (p=.016), and leadership practice (p=.021) increased significantly
      in the experimental group. CONCLUSION: The results show that the Spirituality
      Promotion Program has positive effects on the spiritual and psychosocial aspect
      of young nurses. Continuation of this program for nurses is recommended in order
      to help them develop their selfcare ability and improve nursing competency.

PMID- 25608551
TI  - Reliability and validity of the Korean version of the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire to assess
      Chemotherapy-induced peripheral neuropathy.
AB  - PURPOSE: This study was performed to assess the reliability and validity of the
      Korean version of European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire - Chemotherapy-induced peripheral neuropathy 20
      items (EORTC QLQ-CIPN20) in patients receiving neurotoxic chemotherapy. METHODS:
      A convenience sample of 249 Korean cancer patients, previously or currently,
      being treated with peripheral neurotoxic chemotherapeutic agents were asked to
      fill in the questionnaire. Collected data were analyzed using SPSS 21.0 and AMOS
      21.0. Construct validity, known-group validity, concurrent validity, and internal
      consistency reliability of the Korean version of the QLQ-CIPN20 were evaluated.
      RESULTS: Factor analysis confirmed 3 dimensions of CIPN: sensory, motor, and
      autonomic. The factor loadings of the 20 items on the 3 subscales ranged from .38
      to .85. The 3 subscale-model was validated by confirmatory factor analysis
      (GFI=.90, AGFI=.86, RMSR=.05, NFI=.87, and CFI=.94), and concurrent validity was
      demonstrated with the EORTC QLQ-C30. Furthermore, the QLQ-CIPN20 established
      known-group validity. The Cronbach's alpha coefficients for internal consistency
      of the subscales ranged from .73 to .89. CONCLUSION: The Korean version of the
      EORTC QLQ-CIPN20 showed satisfactory construct, concurrent, and known-group
      validity, as well as internal reliability.

PMID- 25608552
TI  - Trend analysis in the prevalence of type 2 diabetes according to risk factors
      among Korean adults: based on the 2001~2009 Korean National Health and Nutrition
      Examination Survey data.
AB  - PURPOSE: The objective of this study was to provide a trend analysis of the
      prevalence of diabetes relative to the socioeconomic, lifestyle, and physiologic
      risk factors among Korean adults aged over 30 years for a 10-year period using
      data from the Korean National Health and Nutrition Examination Survey. METHODS:
      Prevalence difference and the slope index of inequality were calculated for each
      risk factors using binomial regression by considering the repeated cross
      sectional features of the data. The prevalence ratio and the relative index of
      inequality were calculated using log-binomial regression. Linear trend tests were
      performed using SAS 9.2. RESULTS: Crude prevalence of diabetes increased over the
      10-year period, and was higher for men than for women. It was very high for
      adults 60 years or over, consistently increasing over time. The prevalence among
      unemployed men, women with higher level of stress, women with hypertension, and
      adults with serum triglyceride levels over 135 mg/dL increased over the 10-year
      period in comparison with the respective control group. CONCLUSION: Considering
      the rapid economic development and associated lifestyle changes in Korea, action
      should be taken to control the prevalence of diabetes by both preventing and
      consistently monitoring these identified risk factors using a public-health
      approach.

PMID- 25608553
TI  - Erratum: Synthesis, pharmacokinetics, and biological use of lysine-modified
      single-walled carbon nanotubes [Erratum].
AB  - [This corrects the article on p. 4245 in vol. 9, PMID: 25228803.]. 

PMID- 25608554
TI  - Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator
      activated receptor-loop.
AB  - It is well established that the heart is strongly dependent on fatty acid
      metabolism. In cardiomyocytes there are two distinct sites for the beta
      oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the
      metabolism of these two organelles is believed to be tightly coupled, the nature
      of this relationship has not been fully investigated. Recent research has
      established the significant contribution of mitochondrial function to cardiac ATP
      production under normal and pathological conditions. In contrast, limited
      information is available on peroxisomal function in the heart. This is despite
      these organelles harbouring metabolic pathways that are potentially cardio
      protective, and findings that patients with peroxisomal diseases, such as adult
      Refsum's disease, can develop heart failure. In this article, we provide a
      comprehensive overview on the current knowledge of peroxisomes and the regulation
      of lipid metabolism by PPARs in cardiomyocytes. We also present new experimental
      evidence on the differential expression of peroxisome-related genes in the heart
      chambers and demonstrate that even a mild peroxisomal biogenesis defect
      (Pex11alpha-/-) can induce profound alterations in the cardiomyocyte's
      peroxisomal compartment and related gene expression, including the concomitant
      deregulation of specific PPARs. The possible impact of peroxisomal dysfunction in
      the heart is discussed and a model for the modulation of myocardial metabolism
      via a peroxisome/PPAR-loop is proposed.

PMID- 25608555
TI  - Information-gathering for self-medication via Eastern Indonesian community
      pharmacies: a cross-sectional study.
AB  - BACKGROUND: Gathering sufficient information when handling self-medication
      requests in community pharmacies is an important factor in assisting patients to
      obtain appropriate health outcomes. Common types of information usually gathered
      include patient identity, signs and symptoms, action taken, medical history, and
      current medications being used. The aims of the study were (1) to describe the
      types and amount of information gathered by Eastern Indonesian community pharmacy
      staff when handling self-medication requests, and (2) to identify factors
      associated with the reported amount of information gathered. METHODS: Patient
      simulation and pharmacy staff interviews were used. First, patient simulation was
      conducted using 2 cough scenarios and 1 diarrhoea scenario. Second, a structured
      interview was administered to eligible pharmacy staff in the setting. The types
      and amount of information gathered during patient simulation encounters and
      reported during pharmacy staff interviews were noted. A regression analysis was
      performed to identify factors associated with the amount of information gathered
      from the interview data. RESULTS: The most frequent types of information gathered
      in patient simulation encounters were the nature of symptoms (88% in one of the
      cough scenarios) and patient identity (96% in the diarrhoea scenario). Other
      types of information were gathered in <40% of encounters in each scenario. From
      the pharmacy staff interviews, >90% of the 173 interviewees reported that they
      gathered information on patient identity, nature of symptoms, and associated
      symptoms. Information on medical history and medication used was gathered by 20%
      and 26% respectively of the 173 interviewees. The majority of pharmacy staff
      asked 0 to 2 questions in the patient simulation encounters compared to 5
      questions pharmacy staff reported as their usual practice during the interviews.
      Being qualified as a pharmacist or a pharmacy technician was one of the factors
      positively associated with the reported amount of information gathered.
      CONCLUSION: There were deficits in the types of information gathered when
      pharmacy staff handling self-medication requests. Having a pharmacy educational
      background and additional work experience in the pharmacy was positively
      associated with the reported amount of information gathered. There could be other
      factors contributing to shortcomings in the actual practice which need to be
      explored.

PMID- 25608556
TI  - RECIST measurements in cancer treatment: is there a role for physician
      assistants? - A pilot study.
AB  - BACKGROUND: Decision making in cancer treatment is influenced by standardized
      RECIST measurements which are subjective to interobserver variability. Aim of
      this pilot study was to evaluate whether it is feasible to transfer the
      radiologist's task of RECIST measurements to a trained radiology physician
      assistant and whether this influences diagnostic performance. METHODS: 177
      lesions in twenty patients were measured on baseline and two follow-up CTs using
      RECIST 1.1: Arm A according to routine clinical practice where various
      radiologists read scans of the referred patients. Arm B according to the
      experimental setting where a radiology physician assistant performed RECIST
      measurements of target lesions defined by the radiologists on baseline scans.
      Performance and agreement were compared between groups. RESULTS: Standard
      deviation between lesion measurements of arm A and B was four millimeters.
      Interobserver agreement comparing response category classification was
      substantial, K = 0.77 (95% CI: 0.66 - 0.87). Sensitivity and specificity for the
      radiology physician assistant for assessing progressive disease were 100% (95%
      CI: 61% - 100%) and 94% (95% CI: 81% - 98%) respectively. CONCLUSION: RECIST
      measurements performed by a paramedic are a feasible alternative to standard
      practice. This could impact the workflow of radiological units, opening ways to
      re-assigning radiologists' important, standardized but time consuming tasks to
      paramedics.

PMID- 25608557
TI  - The role of magnetic resonance imaging in the management of brain metastases:
      diagnosis to prognosis.
AB  - This article reviews the different MRI techniques available for the diagnosis,
      treatment and monitoring of brain metastases with a focus on applying advanced MR
      techniques to practical clinical problems. Topics include conventional MRI
      sequences and contrast agents, functional MR imaging, diffusion weighted MR, MR
      spectroscopy and perfusion MR. The role of radiographic biomarkers is discussed
      as well as future directions such as molecular imaging and MR guided high
      frequency ultrasound. 

PMID- 25608558
TI  - Closure of iatrogenic large mucosal and full-thickness defects of the stomach
      with endoscopic interrupted sutures in in vivo porcine models: are they durable
      enough?
AB  - BACKGROUND: In this study, we evaluated the technical feasibility of mucosal
      approximation of large ulcers via an endoscopic suturing system after endoscopic
      submucosal dissection (ESD), assessed the durability of these sutures, and
      compared this technique with serosal apposition of full-thickness gastric wall
      defects using the same device. METHODS: Post-ESD ulcers were closed with mucosal
      apposition in 7 pigs, and endoscopic full-thickness resection (EFTR) defects were
      closed with serosal apposition in 3 pigs. Pigs recovered for 1 week; they were
      then euthanized and necropsies were performed. RESULTS: Primary defect closure
      was achieved in 85.7% of the post-ESD closures and in 100% of the post-EFTR
      closures (p = 0.67). All pigs survived for 1 week. At necropsy, sutures had
      loosened in the post-ESD animals, although only minor deformity of the ulcer
      edges was observed in all repaired post-ESD ulcers. Meanwhile, all of the post
      EFTR defect closures were sustained for 1 week. CONCLUSIONS: Primary closure of
      post-therapeutic defects can be accomplished using the device. Inverted serosal
      apposition provides a more durable and reliable repair than everted mucosal
      apposition.

PMID- 25608559
TI  - Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity
      for mutations in clinically relevant genes.
AB  - BACKGROUND: The extent of intratumoral mutational heterogeneity remains unclear
      in gliomas, the most common primary brain tumors, especially with respect to
      point mutation. To address this, we applied single molecule molecular inversion
      probes targeting 33 cancer genes to assay both point mutations and gene
      amplifications within spatially distinct regions of 14 glial tumors. RESULTS: We
      find evidence of regional mutational heterogeneity in multiple tumors, including
      mutations in TP53 and RB1 in an anaplastic oligodendroglioma and amplifications
      in PDGFRA and KIT in two glioblastomas (GBMs). Immunohistochemistry confirms
      heterogeneity of TP53 mutation and PDGFRA amplification. In all, 3 out of 14
      glial tumors surveyed have evidence for heterogeneity for clinically relevant
      mutations. CONCLUSIONS: Our results underscore the need to sample multiple
      regions in GBM and other glial tumors when devising personalized treatments based
      on genomic information, and furthermore demonstrate the importance of measuring
      both point mutation and copy number alteration while investigating genetic
      heterogeneity within cancer samples.

PMID- 25608560
TI  - Strategies to use tablet computers for collection of electronic patient-reported
      outcomes.
AB  - BACKGROUND: Mobile devices are increasingly being used for data collection in
      research. However, many researchers do not have experience in collecting data
      electronically. Hence, the purpose of this short report was to identify issues
      that emerged in a study that incorporated electronic capture of patient-reported
      outcomes in clinical settings, and strategies used to address the issues.
      FINDINGS: The issues pertaining to electronic patient-reported outcome data
      collection were captured qualitatively during a study on use of electronic
      patient-reported outcomes in two home dialysis units. Fifty-six patients
      completed three surveys on tablet computers, including the Kidney Disease Quality
      of Life-36, the Edmonton Symptom Assessment Scale, and a satisfaction measure.
      Issues that arose throughout the research process were recorded during ethics
      reviews, implementation process, and data collection. Four core issues emerged
      including logistics of technology, security, institutional and financial support,
      and electronic design. CONCLUSIONS: Although use of mobile devices for data
      collection has many benefits, it also poses new challenges for researchers.
      Advance consideration of possible issues that emerge in the process, and
      strategies that can help address these issues, may prevent disruption and enhance
      validity of findings.

PMID- 25608562
TI  - Blood Spotlight on iAMP21 acute lymphoblastic leukemia (ALL), a high-risk
      pediatric disease.
AB  - Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct
      cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia.
      Breakage-fusion-bridge cycles followed by chromothripsis and other complex
      structural rearrangements of chromosome 21 underlie the mechanism giving rise to
      iAMP21. Patients with iAMP21 are older (median age 9 years), with a low white
      cell count. They have a high relapse rate when treated as standard risk. Recent
      studies have shown improved outcome on intensive therapy. Molecular targets for
      therapy are being sought. 

PMID- 25608561
TI  - Mapping interactions between complement C3 and regulators using mutations in
      atypical hemolytic uremic syndrome.
AB  - The pathogenesis of atypical hemolytic uremic syndrome (aHUS) is strongly linked
      to dysregulation of the alternative pathway of the complement system. Mutations
      in complement genes have been identified in about two-thirds of cases, with 5% to
      15% being in C3. In this study, 23 aHUS-associated genetic changes in C3 were
      characterized relative to their interaction with the control proteins factor H
      (FH), membrane cofactor protein (MCP; CD46), and complement receptor 1 (CR1;
      CD35). In surface plasmon resonance experiments, 17 mutant recombinant proteins
      demonstrated a defect in binding to FH and/or MCP, whereas 2 demonstrated reduced
      binding to CR1. In the majority of cases, decreased binding affinity translated
      to a decrease in proteolytic inactivation (known as cofactor activity) of C3b via
      FH and MCP. These results were used to map the putative binding regions of C3b
      involved in the interaction with MCP and CR1 and interrogated relative to known
      FH binding sites. Seventy-six percent of patients with C3 mutations had low C3
      levels that correlated with disease severity. This study expands our knowledge of
      the functional consequences of aHUS-associated C3 mutations relative to the
      interaction of C3 with complement regulatory proteins mediating cofactor
      activity. 

PMID- 25608563
TI  - In vitro culture of stress erythroid progenitors identifies distinct progenitor
      populations and analogous human progenitors.
AB  - Tissue hypoxia induces a systemic response designed to increase oxygen delivery
      to tissues. One component of this response is increased erythropoiesis. Steady
      state erythropoiesis is primarily homeostatic, producing new erythrocytes to
      replace old erythrocytes removed from circulation by the spleen. In response to
      anemia, the situation is different. New erythrocytes must be rapidly made to
      increase hemoglobin levels. At these times, stress erythropoiesis predominates.
      Stress erythropoiesis is best characterized in the mouse, where it is
      extramedullary and utilizes progenitors and signals that are distinct from steady
      state erythropoiesis. In this report, we use an in vitro culture system that
      recapitulates the in vivo development of stress erythroid progenitors. We
      identify cell-surface markers that delineate a series of stress erythroid
      progenitors with increasing maturity. In addition, we use this in vitro culture
      system to expand human stress erythroid progenitor cells that express analogous
      cell-surface markers. Consistent with previous suggestions that human stress
      erythropoiesis is similar to fetal erythropoiesis, we demonstrate that human
      stress erythroid progenitors express fetal hemoglobin upon differentiation. These
      data demonstrate that similar to murine bone marrow, human bone marrow contains
      cells that can generate BMP4-dependent stress erythroid burst-forming units when
      cultured under stress erythropoiesis conditions. 

PMID- 25608564
TI  - Determining the predictors of innovation implementation in healthcare: a
      quantitative analysis of implementation effectiveness.
AB  - BACKGROUND: The failure rates for implementing complex innovations in healthcare
      organizations are high. Estimates range from 30% to 90% depending on the scope of
      the organizational change involved, the definition of failure, and the criteria
      to judge it. The innovation implementation framework offers a promising approach
      to examine the organizational factors that determine effective implementation. To
      date, the utility of this framework in a healthcare setting has been limited to
      qualitative studies and/or group level analyses. Therefore, the goal of this
      study was to quantitatively examine this framework among individual participants
      in the National Cancer Institute's Community Clinical Oncology Program using
      structural equation modeling. METHODS: We examined the innovation implementation
      framework using structural equation modeling (SEM) among 481 physician
      participants in the National Cancer Institute's Community Clinical Oncology
      Program (CCOP). The data sources included the CCOP Annual Progress Reports,
      surveys of CCOP physician participants and administrators, and the American
      Medical Association Physician Masterfile. RESULTS: Overall the final model fit
      well. Our results demonstrated that not only did perceptions of implementation
      climate have a statistically significant direct effect on implementation
      effectiveness, but physicians' perceptions of implementation climate also
      mediated the relationship between organizational implementation policies and
      practices (IPP) and enrollment (p <0.05). In addition, physician factors such as
      CCOP PI status, age, radiological oncologists, and non-oncologist specialists
      significantly influenced enrollment as well as CCOP organizational size and
      structure, which had indirect effects on implementation effectiveness through IPP
      and implementation climate. CONCLUSIONS: Overall, our results quantitatively
      confirmed the main relationship postulated in the innovation implementation
      framework between IPP, implementation climate, and implementation effectiveness
      among individual physicians. This finding is important, as although the model has
      been discussed within healthcare organizations before, the studies have been
      predominately qualitative in nature and/or at the organizational level. In
      addition, our findings have practical applications. Managers looking to increase
      implementation effectiveness of an innovation should focus on creating an
      environment that physicians perceive as encouraging implementation. In addition,
      managers should consider instituting specific organizational IPP aimed at
      increasing positive perceptions of implementation climate. For example, IPP
      should include specific expectations, support, and rewards for innovation use.

PMID- 25608565
TI  - Metadata correction: making big data useful for health care: a summary of the
      inaugural mit critical data conference.

PMID- 25608566
TI  - Medicare and Medicaid enrollment and outside hospitalizations among HIV-infected
      and uninfected veterans engaged in VA care: a retrospective cohort study.
AB  - BACKGROUND: Many veterans engaged in care with the Veterans Administration (VA)
      health system are also enrolled in Medicare and/or Medicaid and may receive care
      both inside and outside of the VA. Use of dual health systems has been associated
      with worse outcomes. Veterans with HIV may have different rates of Medicare and
      Medicaid enrollment and may be at greater risk of poor outcomes related to non-VA
      use. This study compares the frequency and factors associated with Medicare
      and/or Medicaid enrollment and non-VA use in an HIV-infected and uninfected
      population of veterans. METHODS: We used data from the VA and Center for Medicare
      & Medicaid Services from 2004 and 2005 to determine the frequency of Medicare
      and/or Medicaid enrollment among a cohort of HIV-infected and uninfected veterans
      engaged in VA care. We then restricted the cohort to veterans enrolled in fee-for
      service (FFS) Medicare and/or Medicaid with at least one hospitalization and
      identified characteristics associated with non-VA hospital admissions. RESULTS:
      HIV-infected veterans had higher rates of Medicare and/or Medicaid enrollment
      than uninfected veterans (38% vs. 33%, p < 0.01), though the opposite was true
      when our sample was limited to veterans 65 years and older (53% vs. 70%, p < 0.0
      1). Among veterans enrolled in the VA and FFS Medicare and/or Medicaid, veterans
      with HIV had greater illness severity and more frequent hospitalizations, but
      were less likely to be hospitalized outside the VA (48% vs. 54%, p < 0.01). HIV
      infection was associated with lower odds of outside hospitalization (OR = 0.76
      [95% CI: 0.68, 0.85]). CONCLUSIONS: Veterans with HIV have higher rates of
      Medicare and/or Medicaid enrollment, but lower odds of non-VA hospitalization.
      The VA integrated model of HIV care may discourage outside use among HIV-infected
      veterans.

PMID- 25608567
TI  - Chimpanzee population structure in Cameroon and Nigeria is associated with
      habitat variation that may be lost under climate change.
AB  - BACKGROUND: The Nigeria-Cameroon chimpanzee (Pan troglodytes ellioti) is found in
      the Gulf of Guinea biodiversity hotspot located in western equatorial Africa.
      This subspecies is threatened by habitat fragmentation due to logging and
      agricultural development, hunting for the bushmeat trade, and possibly climate
      change. Although P. t. ellioti appears to be geographically separated from the
      neighboring central chimpanzee (P. t. troglodytes) by the Sanaga River, recent
      population genetics studies of chimpanzees from across this region suggest that
      additional factors may also be important in their separation. The main aims of
      this study were: 1) to model the distribution of suitable habitat for P. t.
      ellioti across Cameroon and Nigeria, and P. t. troglodytes in southern Cameroon,
      2) to determine which environmental factors best predict their optimal habitats,
      and 3) to compare modeled niches and test for their levels of divergence from one
      another. A final aim of this study was to examine the ways that climate change
      might impact suitable chimpanzee habitat across the region under various
      scenarios. RESULTS: Ecological niche models (ENMs) were created using the
      software package Maxent for the three populations of chimpanzees that have been
      inferred to exist in Cameroon and eastern Nigeria: (i) P. t. troglodytes in
      southern Cameroon, (ii) P. t. ellioti in northwestern Cameroon, and (iii) P. t.
      ellioti in central Cameroon. ENMs for each population were compared using the
      niche comparison test in ENMtools, which revealed complete niche divergence with
      very little geographic overlap of suitable habitat between populations.
      CONCLUSIONS: These findings suggest that a positive relationship may exist
      between environmental variation and the partitioning of genetic variation found
      in chimpanzees across this region. ENMs for each population were also projected
      under three different climate change scenarios for years 2020, 2050, and 2080.
      Suitable habitat of P. t. ellioti in northwest Cameroon / eastern Nigeria is
      expected to remain largely unchanged through 2080 in all considered scenarios. In
      contrast, P. t. ellioti in central Cameroon, which represents half of the
      population of this subspecies, is expected to experience drastic reductions in
      its ecotone habitat over the coming century.

PMID- 25608568
TI  - Transcriptome analysis of food habit transition from carnivory to herbivory in a
      typical vertebrate herbivore, grass carp Ctenopharyngodon idella.
AB  - BACKGROUND: Although feeding behavior and food habit are ecologically and
      economically important properties, little is known about formation and evolution
      of herbivory. Grass carp (Ctenopharyngodon idella) is an ecologically appealing
      model of vertebrate herbivore, widely cultivated in the world as edible fish or
      as biological control agents for aquatic weeds. Grass carp exhibits food habit
      transition from carnivory to herbivory during development. However, currently
      little is known about the genes regulating the unique food habit transition and
      the formation of herbivory, and how they could achieve higher growth rates on
      plant materials, which have a relatively poor nutritional quality. RESULTS: We
      showed that grass carp fed with duckweed (modeling fish after food habit
      transition) had significantly higher relative length of gut than fish before food
      habit transition or those fed with chironomid larvae (fish without transition).
      Using transcriptome sequencing, we identified 10,184 differentially expressed
      genes between grass carp before and after transition in brain, liver and gut. By
      eliminating genes potentially involved in development (via comparing fish with or
      without food habit transition), we identified changes in expression of genes
      involved in cell proliferation and differentiation, appetite control, circadian
      rhythm, and digestion and metabolism between fish before and after food habit
      transition. Up-regulation of GHRb, Egfr, Fgf, Fgfbp1, Insra, Irs2, Jak, STAT,
      PKC, PI3K expression in fish fed with duckweed, consistent with faster gut
      growth, could promote the food habit transition. Grass carp after food habit
      transition had increased appetite signal in brain. Altered expressions of Per,
      Cry, Clock, Bmal2, Pdp, Dec and Fbxl3 might reset circadian phase of fish after
      food habit transition. Expression of genes involved in digestion and metabolism
      were significantly different between fish before and after the transition.
      CONCLUSIONS: We suggest that the food habit transition from carnivory to
      herbivory in grass carp might be due to enhanced gut growth, increased appetite,
      resetting of circadian phase and enhanced digestion and metabolism. We also found
      extensive alternative splicing and novel transcript accompanying food habit
      transition. These differences together might account for the food habit
      transition and the formation of herbivory in grass carp.

PMID- 25608570
TI  - MR imaging features of intracranial primary CNS lymphoma in immune competent
      patients.
AB  - We aimed to characterize specific MRI findings seen in immune competent patients
      with intracranial primary CNS lymphoma (PCNSL) and to determine their value in
      the management of such patients. Pre-treatment MRI examinations of 21
      immunocompetent patients with biopsy-proven PCNSL were retrospectively evaluated.
      T1 and T2 signal characteristics as well as contrast enhancement features are
      described in all patients. Diffusion, perfusion and proton-MR-spectroscopy
      features are described in a subset of these patients. In the proper clinical and
      radiologic setting, suggesting the diagnosis of PCNSL can help institute proper
      treatment in a timely fashion and avoid unnecessary attempts at surgical
      resection and the associated morbidity. 

PMID- 25608569
TI  - Panobinostat reduces hypoxia-induced cisplatin resistance of non-small cell lung
      carcinoma cells via HIF-1alpha destabilization.
AB  - BACKGROUND: Lung cancer is one of the most frequent cancer types and the leading
      cause of cancer death worldwide. Cisplatin is a widely used chemotherapeutic for
      non-small cell lung carcinoma (NSCLC), however, its positive effects are
      diminished under hypoxia. We wanted to determine if co-treatment with cisplatin
      and histone deacetalyse (HDAC) inhibitor panobinostat can reduce hypoxia-induced
      cisplatin resistance in NSCLC cells, and to elucidate mechanism involved.
      METHODS: Expression status of different HDACS was determined in two cell lines
      and in tumor tissue from 20 patients. Cells were treated with cisplatin,
      panobinostat, or with combination of both under normoxic and hypoxic (1% O(2))
      conditions. Cell cycle, viability, acetylation of histones, and activation of
      apoptosis were determined. HIF-1alpha stability and its interaction with HDAC4
      were analyzed. RESULTS: Most class I and II HDACs were expressed in NSCLC cells
      and tumor samples. Co-treatment of tumor cells with cisplatin and panobinostat
      decreased cell viability and increased apoptosis more efficiently than in
      primary, non-malignant bronchial epithelial cells. Co-treatment induced apoptosis
      by causing chromatin fragmentation, activation of caspases-3 and 7 and PARP
      cleavage. Toxic effects were more pronounced under hypoxic conditions. Co
      treatment resulted in destabilization and degradation of HIF-1alpha and HDAC4, a
      protein responsible for acetylation and de/stabilization of HIF-1alpha. Direct
      interaction between HDAC4 and HIF-1alpha proteins in H23 cells was detected.
      CONCLUSIONS: Here we show that hypoxia-induced cisplatin resistance can be
      overcome by combining cisplatin with panobinostat, a potent HDAC inhibitor. These
      findings may contribute to the development of a new therapeutic strategy for
      NSCLC.

PMID- 25608572
TI  - Strategies to treat thoracic aortitis and infected aortic grafts.
AB  - Infectious thoracic aortitis is a rare disease, especially since the incidence of
      syphilis and tuberculosis has dropped in western countries. However, the risk to
      develop an infectious aortitis and subsequent mycotic aneurysm formation is still
      present, particularly in case of associated endocarditis, sepsis, and in
      immunosuppressive disorders. Moreover, the number of surgical and endovascular
      thoracic aortic repairs is continuously increasing, and infective graft
      complications are observed more frequently. Several etiopathogenetic factors may
      play a role in thoracic aortic and prosthetic infections, including hematogenous
      seeding, local bacterial translocation, and iatrogenous contamination. Also,
      fistulization of the esophagus or the bronchial tree is commonly associated with
      these diseases, and it represents a critical event requiring a multidisciplinary
      management. Knowledge on underlying micro-organisms, antibiotic efficacy, risk
      factors, and prevention strategies has a key role in the management of this
      spectrum of infectious diseases involving the thoracic aorta. When the diagnosis
      of a mycotic aneurysm or a prosthetic graft infection is established, treatment
      is demanding, often including a number of surgical options. Patients are usually
      severely compromised by sepsis, and in most cases they are considered unfit for
      surgery for general clinical conditions or local concerns. Thus, results of
      different therapeutic strategies for infectious diseases of the thoracic aorta
      are still burdened with very high morbidity and mortality. In this manuscript, we
      review the literature regarding the main issues related to thoracic infectious
      aortitis and aortic graft infections, and we report our personal series of
      patients surgically treated at our institution for these conditions from 1993 to
      2014. 

PMID- 25608571
TI  - Usefulness of DWI in preoperative assessment of deep myometrial invasion in
      patients with endometrial carcinoma: a systematic review and meta-analysis.
AB  - BACKGROUND: The objective of this study was to perform a systematic review and a
      meta-analysis in order to estimate the diagnostic accuracy of diffusion weighted
      imaging (DWI) in the preoperative assessment of deep myometrial invasion in
      patients with endometrial carcinoma. METHODS: Studies evaluating DWI for the
      detection of deep myometrial invasion in patients with endometrial carcinoma were
      systematically searched for in the MEDLINE, EMBASE, and Cochrane Library from
      January 1995 to January 2014. Methodologic quality was assessed by using the
      Quality Assessment of Diagnostic Accuracy Studies tool. Bivariate random-effects
      meta-analytic methods were used to obtain pooled estimates of sensitivity,
      specificity, diagnostic odds ratio (DOR) and receiver operating characteristic
      (ROC) curves. The study also evaluated the clinical utility of DWI in
      preoperative assessment of deep myometrial invasion. RESULTS: Seven studies
      enrolling a total of 320 individuals met the study inclusion criteria. The
      summary area under the ROC curve was 0.91. There was no evidence of publication
      bias (P = 0.90, bias coefficient analysis). Sensitivity and specificity of DWI
      for detection of deep myometrial invasion across all studies were 0.90 and 0.89,
      respectively. Positive and negative likelihood ratios with DWI were 8 and 0.11
      respectively. In patients with high pre-test probabilities, DWI enabled
      confirmation of deep myometrial invasion; in patients with low pre-test
      probabilities, DWI enabled exclusion of deep myometrial invasion. The worst case
      scenario (pre-test probability, 50%) post-test probabilities were 89% and 10% for
      positive and negative DWI results, respectively. CONCLUSION: DWI has high
      sensitivity and specificity for detecting deep myometrial invasion and more
      importantly can reliably rule out deep myometrial invasion. Therefore, it would
      be worthwhile to add a DWI sequence to the standard MRI protocols in preoperative
      evaluation of endometrial cancer in order to detect deep myometrial invasion,
      which along with other poor prognostic factors like age, tumor grade, and LVSI
      would be useful in stratifying high risk groups thereby helping in the tailoring
      of surgical approach in patient with low risk of endometrial carcinoma.

PMID- 25608573
TI  - Advances in the treatment of Helicobacter pylori infection in children.
AB  - In this review we elaborate on two main questions concerning the management of
      Helicobacter pylori infection in children. First, we focus on who should be
      treated. In the presence of Helicobacter pylori (H. pylori)-associated peptic
      ulcer disease, eradication of the micro-organism is recommended. When H. pylori
      infection is detected by biopsy-based methods in the absence of peptic ulcer
      disease in a child with dyspeptic symptoms, treatment of H. pylori infection may
      be considered. In infected children whose first degree relatives have gastric
      cancer, treatment can be offered. A 'test-and-treat' strategy is not and has
      never been recommended in children. The second issue to address is what the
      recommended treatments are. ESPGHAN/NASPGHAN recommends that treatment tailored
      to susceptibility testing should be the first choice in pediatric patients. The
      duration of therapy should be 10-14 days. Costs, compliance and adverse effects
      should be taken into account. Checking the result of eradication with a reliable
      non-invasive test such as the 13C urea breath test, is recommended at least 4-8
      weeks following completion of therapy.

PMID- 25608574
TI  - Diagnosis and treatment of congenital abdominal aortic aneurysm: a systematic
      review of reported cases.
AB  - BACKGROUND: Congenital abdominal aortic aneurysm (AAA) is distinctly rare in
      infants and children and carries a high mortality rate. Our objective was to
      summarize the experience of the diagnosis and treatment in patients with
      congenital AAA. METHODS: Reported cases of congenital AAA published prior to
      November 8, 2014, were identified through PubMed, EMBASE, Web of Science, and
      reference lists. All selected cases were evaluated for main clinical
      characteristics. RESULTS: Twenty-six cases of congenital AAA were identified in
      the English language literature. Congenital AAA occurred primarily in children
      under three years old, but it was also found in young adults and fetuses. With
      regards to the localization, the great majority of congenital AAA was infrarenal
      AAA. The majority of the AAA patients lacked specific symptoms, and a painless
      pulsatile abdominal mass was the most common clinical presentation. The diagnosis
      of AAA was based on ultrasound scanning in twenty-five cases, multi-slice spiral
      computed tomography angiography (MSCTA) in sixteen cases, and magnetic resonance
      angiography (MRA) in nine cases. Histopathological analyses were available in
      seven cases. Seven patients received conservative management. Surgical treatment
      was performed in seventeen cases, and open repair with an artificial graft was
      the main surgical intervention. The mortality associated with congenital AAA was
      high (30.76%). Ruptured aneurysm and renal failure were the main causes of death.
      CONCLUSIONS: Good outcomes can be achieved in children with early identification
      of congenital AAA and individualized surgical repair with grafts.

PMID- 25608576
TI  - A rare case of colonic pseudolipomatosis.

PMID- 25608577
TI  - Controlling the metal to semiconductor transition of MoS2 and WS2 in solution.
AB  - Lithiation-exfoliation produces single to few-layered MoS2 and WS2 sheets
      dispersible in water. However, the process transforms them from the pristine
      semiconducting 2H phase to a distorted metallic phase. Recovery of the
      semiconducting properties typically involves heating of the chemically exfoliated
      sheets at elevated temperatures. Therefore, it has been largely limited to sheets
      deposited on solid substrates. Here, we report the dispersion of chemically
      exfoliated MoS2 sheets in high boiling point organic solvents enabled by surface
      functionalization and the controllable recovery of their semiconducting
      properties directly in solution. This process connects the scalability of
      chemical exfoliation with the simplicity of solution processing, ultimately
      enabling a facile method for tuning the metal to semiconductor transitions of
      MoS2 and WS2 within a liquid medium. 

PMID- 25608579
TI  - Influences of porous structurization and Pt addition on the improvement of
      photocatalytic performance of WO3 particles.
AB  - Tungsten trioxide (WO3) displays excellent performance in solar-related material
      applications. However, this material is rare and expensive. Therefore, developing
      efficient materials using smaller amounts of WO3 is inevitable. In this study, we
      investigated how to create high photocatalytic performance of WO3 particles
      containing platinum (Pt, as a co-catalyst) and homogeneously spherical macropores
      (as a medium to enable access of large molecules and light penetration into the
      remote internal regions of the catalyst). The present particles were prepared by
      spray drying of a precursor solution containing WO3 nanoparticles, Pt solution,
      and polystyrene (PS) spheres (as a colloidal template). Photocatalytic studies
      showed that changes in particle morphology (from dense with smooth surfaces, to
      dense with rough surfaces, to porous structures) and added Pt effectively
      improved the photocatalytic performance over WO3 nanoparticles. Our results
      showed that the best precursor (prepared using a PS/WO3 mass ratio of 0.32 and
      containing Pt co-catalyst) provided WO3 particles with a photocatalytic rate of
      more than 5 times that of pure 10 nm WO3 nanoparticles. Moreover, the catalyst
      can be effectively recycled without an apparent decrease in its photocatalytic
      activity. The experimental results were also supported by a proposal mechanism of
      the photocatalytic reaction phenomenon. 

PMID- 25608575
TI  - Cardiovascular dysfunction in patients with liver cirrhosis.
AB  - Hyperdynamic syndrome is a well-known clinical condition found in patients with
      cirrhosis and portal hypertension, characterized by increased heart rate and
      cardiac output, and reduced systemic vascular resistance and arterial blood
      pressure. The leading cause of hyperdynamic circulation in cirrhotic patients is
      peripheral and splanchnic vasodilatation, due to an increased production/activity
      of vasodilator factors and decreased vascular reactivity to vasoconstrictors. The
      term "cirrhotic cardiomyopathy" describes impaired contractile responsiveness to
      stress, diastolic dysfunction and electrophysiological abnormalities in patients
      with cirrhosis without known cardiac disease. Underlying circulatory and cardiac
      dysfunctions are the main determinant in the development of hepatorenal syndrome
      in advanced cirrhosis. Moreover, the clinical consequences of cirrhosis-related
      cardiovascular dysfunction are evident during and after liver transplantation,
      and after transjugular intrahepatic portosystemic shunt insertion. Cardiovascular
      complications following these procedures are common, with pulmonary edema being
      the most common complication. Other complications include overt heart failure,
      arrhythmia, pulmonary hypertension, pericardial effusion, and cardiac thrombus
      formation. This review discusses the circulatory and cardiovascular dysfunctions
      in cirrhosis, examining the pathophysiologic and clinical implications in light
      of the most recent published literature.

PMID- 25608580
TI  - Predicting long-term outcomes of acute aortic dissection: a focus on gender.
AB  - Acute aortic disease ranks as the 19th leading cause of death with steadily
      increasing incidence. The prevalence of aneurysms varies depending on the
      localization along the aorta with a mortality of aortic rupture of around 80%.
      Traditionally, aortic disease affects men more frequently than women, however,
      with a varying gender ratio. Nevertheless, in the setting of acute aortic
      dissection, the International Registry of Acute Aortic Dissections identified
      significant gender-related differences in the management of both sexes with acute
      aortic conditions. Current data suggest that women are at an increased risk of
      both dying from aortic dissection and having aorta-related complications than
      men. This review aims to report on current evidence of gender impact on natural
      history, treatment and outcomes in patients with acute aortic dissection. 

PMID- 25608582
TI  - Deep breathing: A simple test for white coat effect detection in primary care.
AB  - AIM: White coat hypertension (WCH) is hard to differentiate from sustained
      hypertension without the use of 24-h ambulatory blood pressure monitoring (ABPM).
      This invaluable procedure is nevertheless cumbersome and expensive. A simple test
      of deep breathing over 30 s (DBT) was proposed as a method to unveil WCH.
      METHODS: Two hundred and fourteen outpatients referred for the evaluation of
      uncontrolled hypertension (blood pressure, BP > 140/90 mmHg despite therapy) were
      enrolled in a controlled clinical trial. The examinees were randomly divided in
      two groups: control (n = 108; sequential standard BP measurement only) and
      intervention (n = 106; the same+DBT), using ABPM as the reference standard.
      RESULTS: The relative decrease in BP was significantly larger in the intervention
      group than in the control group, by 15/4 mmHg (p = 0.005). The best detection of
      WCH was obtained at >= 15% systolic BP reduction following DBT, with a positive
      predictive value of 94.0% (95% CI 72.0-100.0). BP reduction of <= 8% may rule WCH
      out with a negative predictive value of 78.4% (95% CI 64.0 - 85.9). CONCLUSION:
      DBT is a reliable, inexpensive and fast test for the detection of WCH in primary
      care.

PMID- 25608581
TI  - Molecular and phenotypic characterization of human amniotic fluid-derived cells:
      a morphological and proteomic approach.
AB  - Mesenchymal Stem Cells derived from Amniotic Fluid (AFMSCs) are multipotent cells
      of great interest for regenerative medicine. Two predominant cell types, that is,
      Epithelial-like (E-like) and Fibroblast-like (F-like), have been previously
      detected in the amniotic fluid (AF). In this study, we examined the AF from 12
      donors and observed the prevalence of the E-like phenotype in 5, whereas the F
      like morphology was predominant in 7 samples. These phenotypes showed slight
      differences in membrane markers, with higher CD90 and lower Sox2 and SSEA-4
      expression in F-like than in E-like cells; whereas CD326 was expressed only in
      the E-like phenotype. They did not show any significant differences in
      osteogenic, adipogenic or chondrogenic differentiation. Proteomic analysis
      revealed that samples with a predominant E-like phenotype (HC1) showed a
      different profile than those with a predominant F-like phenotype (HC2). Twenty
      five and eighteen protein spots were differentially expressed in HC1 and HC2
      classes, respectively. Of these, 17 from HC1 and 4 from HC2 were identified by
      mass spectrometry. Protein-interaction networks for both phenotypes showed strong
      interactions between specific AFMSC proteins and molecular chaperones, such as
      preproteasomes and mature proteasomes, both of which are important for cell cycle
      regulation and apoptosis. Collectively, our results provide evidence that,
      regardless of differences in protein profiling, the prevalence of E-like or F
      like cells in AF does not affect the differentiation capacity of AFMSC
      preparations. This may be valuable information with a view to the therapeutic use
      of AFMSCs. 

PMID- 25608583
TI  - Antiviral activity and CSF concentrations of 600/100 mg of darunavir/ritonavir
      once daily in HIV-1 patients with plasma viral suppression.
AB  - OBJECTIVES: The objective of this study was to assess whether a lower dose than
      the currently used one of darunavir/ritonavir might achieve good CSF
      concentrations and contribute to inhibition of CNS viral replication. PATIENTS
      AND METHODS: This was a substudy of a randomized, open, multicentre study
      (eudraCT 2011-006272-39), comparing the efficacy and safety of 800/100 mg of
      darunavir/ritonavir (darunavir 800) versus 600/100 mg of darunavir/ritonavir
      (darunavir 600) once daily plus tenofovir/emtricitabine or abacavir/lamivudine in
      100 virologically suppressed patients. Paired blood and CSF samples were
      obtained. Total plasma darunavir concentrations were determined by HPLC, and CSF
      concentrations by liquid chromatography-tandem MS. Viral load (VL) was determined
      in plasma and CSF (limit of detection = 40 copies/mL) by PCR. RESULTS: Sixteen
      patients were enrolled. The median (range) of darunavir CSF concentrations in
      darunavir 600 (n = 8) and darunavir 800 (n = 8) patients was 17.08 (5.79-30.19)
      and 13.23 (3.47-32.98) ng/mL, respectively (P = 0.916). The median (range)
      darunavir CSF:plasma ratio was 0.010 (0.005-0.022) in darunavir 600 patients and
      0.008 (0.004-0.017) in the darunavir 800 arm (P = 0.370). All 16 patients had a
      VL < 40 copies/mL in plasma and 14 had a VL < 40 copies/mL in CSF. Of the two
      patients with detectable CSF VL (280 copies/mL and 159 copies/mL), one was
      receiving darunavir 600 and the other darunavir 800 plus tenofovir/emtricitabine.
      Of note, these patients had the lowest CSF darunavir concentrations in their
      respective groups: 5.79 ng/mL (802 ng/mL in plasma) and 3.47 ng/mL (958 ng/mL in
      plasma). CONCLUSIONS: Darunavir CSF and plasma concentrations were comparable
      between the two arms. However, one patient from each group (with the lowest CSF
      darunavir concentrations in their respective groups) had detectable CSF VL
      despite undetectable plasma VL.

PMID- 25608584
TI  - Plasma and target-site subcutaneous tissue population pharmacokinetics and dosing
      simulations of cefazolin in post-trauma critically ill patients.
AB  - OBJECTIVES: The objective of this study was to describe the population
      pharmacokinetics of cefazolin in plasma and the interstitial fluid of
      subcutaneous tissue of post-trauma critically ill patients and provide clinically
      relevant dosing recommendations that result in optimal concentrations at the
      target site. PATIENTS AND METHODS: This was a pharmacokinetic study in a tertiary
      referral ICU. We recruited 30 post-trauma critically ill adult patients and
      collected serial total and unbound plasma cefazolin concentrations. Interstitial
      fluid concentrations were determined using in vivo microdialysis. Population
      pharmacokinetic analysis and Monte Carlo simulations were undertaken with
      Pmetrics((r)). Fractional target attainment against an MIC distribution for
      Staphylococcus aureus isolates was calculated. RESULTS: The mean (SD) age,
      weight, APACHE II score and CLCR were 37.0 (14.1) years, 86.8 (22.7) kg, 16.9
      (5.3) and 163 (44) mL/min, respectively. A three-compartment linear population
      pharmacokinetic model was most appropriate. Covariates included in the model were
      CLCR on drug clearance and serum albumin concentration and body weight on the
      volume of the central compartment. The fractional target attainment for a 1 g
      intravenous 8-hourly dose for a CLCR of 50 mL/min was 88%, whereas for a patient
      with a CLCR of 215 mL/min, a dose of 2 g 6-hourly achieved 84% fractional target
      attainment. CONCLUSIONS: Clinicians should be mindful of the effects of elevated
      CLCR and serum albumin concentrations on dosing requirements for post-trauma
      critically ill patients.

PMID- 25608585
TI  - Performance of commonly used genotypic assays and comparison with phenotypic
      assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients.
AB  - OBJECTIVES: Although founder viruses in primary HIV-1 infections (PHIs) typically
      use the CCR5 coreceptor (R5-tropic), 3%-19% of subjects also harbour CXCR4-using
      viruses (X4-tropic), making tropism determination before CCR5 antagonist usage
      mandatory. Genotypic methods can be used to accurately determine HIV-1 tropism in
      chronically infected patients. METHODS: We compared the results of genotypic
      methods [geno2pheno, PSSMx4r5 including a novel nucleotide-input version (ntPSSM)
      and distant segments (ds)Kernel] to predict coreceptor usage in a cohort of 67
      PHIs. Specimens with discrepant results were phenotypically tested after cloning
      the V3 gene region into proviral backbones. Recombinant viruses were used to
      infect U87 indicator cell lines bearing CD4 and either CCR5 or CXCR4. RESULTS:
      Geno2pheno10%, PSSMx4r5 and (ds)Kernel gave identical predictions in 85% of
      cases. Geno2pheno10% predicted the presence of CXCR4 viruses in 18% of patients.
      Two patients were predicted to carry X4-tropic viruses by all algorithms and X4
      tropic viruses were detected in at least one of the recombinant AD8 or NL4-3
      backbone-based assays. Ten samples resulted in discordant predictions with at
      least one algorithm. Full concordance between tropism prediction by using
      population sequencing and phenotypic assays was observed only with ntPSSM.
      Geno2pheno prediction and the phenotypic assay gave the same results in a
      minority of 'discordant' patients. CONCLUSIONS: Compared with both PSSMx4r5
      versions, (ds)Kernel and our phenotypic assay, geno2pheno10% overestimated the
      frequency of X4-tropic viruses (18% versus 3%). ntPSSM was able to detect one
      additional X4 virus compared with (ds)Kernel that was confirmed with the
      phenotypic assay.

PMID- 25608586
TI  - Characterization of KPC-type carbapenemase-producing Klebsiella pneumoniae
      strains isolated in the Arabian Peninsula.

PMID- 25608587
TI  - Isoniazid treatment to prevent TB in kidney and pancreas transplant recipients
      based on an interferon-gamma-releasing assay: an exploratory randomized
      controlled trial.
AB  - BACKGROUND: We performed a randomized trial of isoniazid treatment based on
      interferon-gamma-releasing assay (IGRA) in kidney transplant (KT) recipients in
      an intermediate-TB-burden country. METHODS: All adult patients admitted to a KT
      institute between June 2010 and May 2013 were enrolled. The IGRA (T-SPOT.TB
      assay) was performed on all patients, and isoniazid treatment was given to those
      with clinical risk factors for latent TB infection (LTBI). Patients with positive
      IGRA who had no clinical risk factors for LTBI were randomly assigned to
      isoniazid treatment or a control group. The development of TB after KT was
      monitored between June 2010 and November 2013. The primary endpoint was the
      development of TB. RESULTS: Of the 784 patients who had no clinical risk factors
      for LTBI, 445 (57%) gave negative results in the IGRA, 76 (10%) indeterminate
      results and 263 (33%) positive results. Of the latter, 131 were allocated to
      isoniazid treatment and 132 to the control group. Three (2%) of the control group
      developed TB, whereas none of the isoniazid treatment group developed TB (rate
      difference 1.22 per 100 person-years, P = 0.09). Of the 521 patients with
      negative or indeterminate IGRA results, 4 [0.8%, 0.43 per 100 person-years (95%
      CI 0.12-1.09)] developed TB after KT. CONCLUSIONS: IGRA-based isoniazid treatment
      has a trend towards reducing TB development in KT recipients without clinical
      risk factors, but careful monitoring of TB development is needed in negative-IGRA
      KT recipients.

PMID- 25608588
TI  - Anthelmintic resistance in equine helminth parasites - a growing issue for horse
      owners and veterinarians in New Zealand?
AB  - There is growing concern that given the high frequency with which anthelmintics
      are being administered to many horses, anthelmintic resistance amongst equine
      helminth populations will be an increasing problem, rendering many of the
      currently available products unusable with little prospect of new products
      becoming available, at least in the near future. Worldwide, much reliance has
      been placed on the macrocyclic lactone (ML) group of anthelmintics, but
      resistance has been reported to these products as well as to the two other major
      anthelmintic classes used in this species, the benzimidazoles (BZ) and the
      tetrahydropyrimidines (e.g. pyrantel). In New Zealand, resistance has been
      reported to the ML and BZ groups, but not yet to pyrantel. As an alternative to
      interval-based anthelmintic regimens, the highly overdispersed nature of parasite
      populations in horses can be utilised to decide whether treatment is required,
      based on whether or not animals exceed a predetermined level of shedding of
      parasite eggs. If well managed, such a targeted and selective approach can be
      utilised to eliminate the majority of egg output whilst still providing a refuge
      for susceptible parasites to persist. Such a system would require that an
      adequate standard of monitoring be in place and cognisance needs to be taken of
      parasites or their lifecycle stages that cannot be diagnosed by routine methods.
      At the same time, using anthelmintics with high levels of efficacy, avoiding
      practices such as under-dosing, as well as utilising non-chemical means of
      parasite control when possible, e.g. regular removal of faeces from pasture,
      should all be considered. Combinations of anthelmintics, specifically of
      anthelmintics that target the same or a similar spectrum of parasite species,
      should play an important role in parasite control in horses. As well as providing
      arguably the highest levels of efficacy, combinations may also slow the rate at
      which anthelmintic resistance develops. 

PMID- 25608589
TI  - The Healthy Lifestyles Programme (HeLP)--an overview of and recommendations
      arising from the conceptualisation and development of an innovative approach to
      promoting healthy lifestyles for children and their families.
AB  - Despite the rise in childhood obesity, there remains a paucity of evidence for
      effective interventions that engage children and parents sufficiently to make and
      sustain lifestyle behaviour change. The Healthy Lifestyles Programme (HeLP) is a
      school-located obesity prevention programme, which has been developed with
      teachers, families and healthcare professionals. The underpinning assumption in
      the development of HeLP was to take a relational approach to changing behaviour,
      building relationships with the schools, children and their families to create
      supportive environments for healthy lifestyle choices. Thus, HeLP was
      conceptualised as a complex intervention within a complex system and developed as
      a dynamic, evolving set of processes to support and motivate children towards
      healthy behaviours. The delivery methods used are highly interactive and
      encourage identification with and ownership of the healthy lifestyle messages so
      that the children are motivated to take them home to their parents and effect
      change within the family. We have good evidence that HeLP engages schools and
      children such that they want to participate in the Programme. Results from an
      exploratory trial showed that the Programme is feasible and acceptable and has
      the potential to change behaviours and affect weight status. This paper presents
      an overview of and recommendations arising from the conceptualization;
      development and evaluation of the Healthy Lifestyles Programme as part of a
      special issue focusing on novel approaches to the global problem of childhood
      obesity. 

PMID- 25608590
TI  - Could a deletion in neuraminidase stalk strengthen human tropism of the novel
      avian influenza virus H7N9 in China, 2013?
AB  - Objective. A novel avian influenza A virus (AIV) H7N9 subtype which emerged in
      China in 2013 caused worldwide concern. Deletion of amino-acids 69 to 73 in the
      neuraminidase stalk was its most notable characteristic. This study is aimed to
      discuss the tropism and virulence effects of this deletion. METHODS:
      Neuraminidase gene sequences of N9 subtype were collected from NCBI and GISAID.
      MEGA6.0, Stata12.0, and UCSF Chimera were employed for sequence aligning,
      significance testing, and protein tertiary structure homology modeling. RESULTS:
      A total of 736 sequences were obtained; there were 81 human isolates of the novel
      AIV H7N9, of which 79 had the deletion. Among all the 654 avian origin sequences,
      only 43 had the deletion (p < 0.001). Tertiary structure displayed that the
      deletion obviously changed the spatial direction of neuraminidase. CONCLUSIONS:
      The deletion in neuraminidase stalk could have strengthened human tropism of the
      novel AIV H7N9, as well as its virulence.

PMID- 25608591
TI  - Ethanol and acetic acid production from carbon monoxide in a Clostridium strain
      in batch and continuous gas-fed bioreactors.
AB  - The effect of different sources of nitrogen as well as their concentrations on
      the bioconversion of carbon monoxide to metabolic products such as acetic acid
      and ethanol by Clostridium autoethanogenum was studied. In a first set of assays,
      under batch conditions, either NH4Cl, trypticase soy broth or yeast extract (YE)
      were used as sources of nitrogen. The use of YE was found statistically
      significant (p < 0.05) on the product spectrum in such batch assays. In another
      set of experiments, three bioreactors were operated with continuous CO supply, in
      order to estimate the effect of running conditions on products and biomass
      formation. The bioreactors were operated under different conditions, i.e., EXP1
      (pH = 5.75, YE 1g/L), EXP2 (pH = 4.75, YE 1 g/L) and EXP3 (pH = 5.75, YE 0.2
      g/L). When compared to EXP2 and EXP3, it was found that EXP1 yielded the maximum
      biomass accumulation (302.4 mg/L) and products concentrations, i.e., acetic acid
      (2147.1 mg/L) and ethanol (352.6 mg/L). This can be attributed to the fact that
      the higher pH and higher YE concentration used in EXP1 stimulated cell growth and
      did, consequently, also enhance metabolite production. However, when ethanol is
      the desired end-product, as a biofuel, the lower pH used in EXP2 was more
      favourable for solventogenesis and yielded the highest ethanol/acetic acid ratio,
      reaching a value of 0.54. 

PMID- 25608592
TI  - Assessing health impacts within environmental impact assessments: an opportunity
      for public health globally which must not remain missed.
AB  - Within the member states of the United Nations 190 of 193 have regulated
      Environmental Impact Assessments (EIA) which is a systematic process to prevent
      and mitigate the potential environmental impacts of industry development projects
      before these occur. However, the routine and comprehensive assessment of health
      impacts within EIAs remains underdeveloped. Focusing, as an example, on the risks
      to global health from the global shift in the mining industry towards Low and
      Middle Income Countries LMIC), this viewpoint details why connecting with EIA is
      an essential task for the health system. Although existing knowledge is out of
      date in relation to global practice we identify how health has been included, to
      some extent, in High Income Country EIAs and the institutional requirements for
      doing so. Using arguments identified by industry themselves about requiring a
      'social license to operate', we conclude that EIA regulations provide the best
      current mechanism to ensure health protection is a core aspect in the decision
      making process  to approve projects. 

PMID- 25608593
TI  - Opposing motion inhibits responses of direction-selective ganglion cells in the
      fish retina.
AB  - Inhibitory influences in receptive fields (RFs) of the fish retinal direction
      selective ganglion cells (DS GCs) were investigated. Responses of the fast
      retinal DS GCs were recorded extracellularly from their axon terminals in the
      superficial layer of tectum opticum of immobilized fish. The data were collected
      from two cyprinid species - Carassius gibelio, a wild form of the goldfish, and
      the barbel fish Labeobarbus intermedius. Visual stimuli were presented to the
      fish on the monitor screen within a square area of stimulation occupying
      approximately 11 * 11 degrees  of the visual field. DS GCs were stimulated by
      pairs of narrow stripes moving in opposing directions. One of them entered
      central (responsive) area of cell receptive field (RRF) from the preferred, and
      the other one from the null side. Stimuli merged at center of stimulation area,
      and subsequently moved away from each other. It was shown that the cell response
      evoked by the stripe coming from the preferred side of RF was inhibited by the
      stimulus coming from the opposite direction. In the majority of units recorded
      inhibitory effect induced by the null-side stimulus was initiated in the RF
      periphery. As a rule, inhibitory influences sent from the RF periphery were
      spread across the entire central area of RF. Modifications of the inhibitory
      influences were investigated throughout the whole motion of paired stimuli.
      Evident inhibitory effects mediated from the null direction were recorded during
      the approach of stimuli. When stripes crossed each other and moved apart
      inhibition was terminated, and cell response appeared again. Null-side inhibition
      observed in fish DS GCs is most likely induced by starburst-like amacrine cells
      described in morphological studies of different fish species. Possible mechanisms
      underlying direction selectivity in fish DS GCs are discussed. 

PMID- 25608594
TI  - Synthesis of indoles, benzofurans, and related heterocycles via an acetylene
      activated SNAr/intramolecular cyclization cascade sequence in water or DMSO.
AB  - The synthesis of 2-substituted indoles and benzofurans was achieved by
      nucleophilic aromatic substitution, followed by subsequent 5-endo-dig cyclization
      between the nucleophile and an ortho acetylene. The acetylene serves the dual
      role of the electron withdrawing group to activate the substrate for SNAr, and
      the C1-C2 carbon scaffold for the newly formed 5-membered heteroaromatic ring.
      This method allows for the bond forming sequence of Ar-X-N/O-C1 to proceed in a
      single synthetic step, furnishing indoles and benzofurans in moderate to high
      yields. Since the method is not transition metal mediated, brominated and
      chlorinated substrates are tolerated, and benzofuran formation can be conducted
      using water or water-DMSO mixtures as solvent. 

PMID- 25608595
TI  - Proteomic analysis of the copper resistance of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a Gram-positive bacterial pathogen causing a variety
      of diseases, including otitis media, bacteraemia and meningitis. Although copper
      is an essential trace metal for bacterial growth, high intracellular levels of
      free-copper are toxic. Copper resistance has emerged as an important virulence
      determinant of microbial pathogens. In this study, we determined the minimum
      inhibition concentration of copper for the growth inhibition of S. pneumoniae.
      Two-dimensional-electrophoresis coupled with mass spectrometry was applied to
      identify proteins involved in copper resistance of S. pneumoniae. In total, forty
      four proteins with more than 1.5-fold alteration in expression (p < 0.05) were
      identified. Quantitative reverse transcription PCR was used to confirm the
      proteomic results. Bioinformatics analysis showed that the differentially
      expressed proteins were mainly involved in the cell wall biosynthesis, protein
      biosynthesis, purine biosynthesis, pyrimidine biosynthesis, primary metabolic
      process, and the nitrogen compound metabolic process. Many up-regulated proteins
      in response to the copper treatment directly or indirectly participated in the
      cell wall biosynthesis, indicating that the cell wall is a critical determinant
      in copper resistance of S. pneumoniae. 

PMID- 25608596
TI  - Clinical evaluation of eight different D-dimer tests for the exclusion of deep
      venous thrombosis in primary care patients.
AB  - D-dimer tests are an essential element in the diagnostic work-up of deep venous
      thrombosis (DVT). However, the poor standardization amongst assays necessitates
      clinical validation before implementation in daily practice. We therefore
      evaluated the analytical and diagnostic performance of eight D-dimer tests in a
      representative group of 290 prospectively identified consecutive primary care
      patients with suspected DVT. Seven quantitative D-dimer assays, and a qualitative
      test, Simplify, were evaluated. Correlation between assays was generally poor and
      several assays showed a significant bias in the method comparison. Nevertheless,
      the Vidas D-dimer, Innovance D-dimer (CA1500 and BCS), Pathfast D-dimer, and
      HemosIL HS500 (ACL TOP), all displayed 100% (95% CI: 85-100%) sensitivity. Tina
      quant (Modular), AQT90 D-dimer, and Liatest (STA((r))) D-dimer tests showed a
      slightly lower sensitivity of 95% (78-100%). and the Simplify test reached a
      sensitivity of 91% (72-99%) that was further improved in combination with a
      clinical decision rule to 95% (76-100%). In concert with the low (8.2%)
      prevalence of proximal DVT, diagnosed by compression ultrasonography, in our
      study, all test reached a negative predictive value (NPV) of at least 99%. The
      user friendliness of the assays differed mainly by stability of reagents,
      calibration frequency, time required to obtain a test result and costs of a test.
      In conclusion, despite considerable analytical differences, in our low-risk
      population all tests evaluated displayed an excellent NPV. In combination with a
      validated clinical decision rule to identify low-risk patients, even a
      straightforward POC solution could safely and cost-efficiently rule out DVT.

PMID- 25608597
TI  - Six-day stability of erythrocyte and reticulocyte parameters in-vitro: a
      comparison of blood samples from healthy, iron-deficient, and thalassemic
      individuals.
AB  - INTRODUCTION: Stability for up to 6 days' storage of erythrocyte and reticulocyte
      parameters in samples from iron-deficient and thalassemic individuals has not yet
      been reported. This lack of knowledge challenges evaluation of the full blood
      count in referral samples for hemoglobinopathy evaluation. We therefore hereby
      present such sample stability data. METHODS: We included fresh (less than 4 hours
      old) blood samples from eight healthy, eight iron-deficient, and 11 thalassemic
      individuals. A full blood count, including reticulocyte parameters, was performed
      on a Sysmex XE-2100 once daily during a 6-day storage period at room temperature.
      For healthy individuals, we also studied stability of refrigerated samples and
      investigated analytical and biological variation. RESULTS: Hemoglobin
      concentration, erythrocyte count, and mean corpuscular hemoglobin were stable for
      6 days in all diagnostic groups. Mean corpuscular volume increased less in
      samples from iron-deficient individuals while the number of reticulocytes
      increased more in samples from thalassemic, as compared to healthy individuals.
      Ret-He stability depended on its baseline value. Within-person biological
      variation in samples from healthy individuals was low both for erythrocyte
      parameters and for reticulocyte hemoglobin, while higher for reticulocyte counts.
      CONCLUSION: Results for hemoglobin concentration, erythrocyte count, and mean
      corpuscular hemoglobin are reliable in hemoglobinopathy investigation of referred
      samples for up to 6 days. Storage time-dependent changes of other erythrocyte and
      reticulocyte parameters in blood samples from iron-deficient and thalassemic
      individuals differ from those of healthy individuals.

PMID- 25608598
TI  - Hemolysis indexes for biochemical tests and immunoassays on Roche analyzers:
      determination of allowable interference limits according to different calculation
      methods.
AB  - OBJECTIVES: To determine the hemolysis interference on biochemical tests and
      immunoassays performed on Roche Diagnostics analyzers, according to different
      maximum allowable limits. DESIGN AND METHODS: Heparinized plasma and serum pools,
      free of interferences, were overloaded by increasing amounts of a hemoglobin
      titrated hemolysate. This interference was evaluated for 45 analytes using
      Modular((r)) and Cobas((r)) analyzers. For each parameter, the hemolysis index
      (HI) corresponding to the traditional +/- 10% change of concentrations from
      baseline (+/- 10%Delta) was determined, as well as those corresponding to the
      analytical change limit (ACL), and to the reference change value (RCV). Then, the
      relative frequencies distribution (% RFD) of hemolyzed tests performed in a
      hospital laboratory over a 25-day period were established for each HI as
      allowable limit. RESULTS: Considering the +/- 10%Delta, the analyte
      concentrations enhanced by hemolysis were: Lactate dehydrogenase (LDH), aspartate
      aminotransferase (AST), folate, potassium, creatine kinase, phosphorus, iron,
      alanine aminotransferase, lipase, magnesium and triglycerides, decreasingly. The
      analyte concentrations decreased by hemolysis were: Haptoglobin, high-sensitive
      troponin T and alkaline phosphatase. Over the 25-day period, the % RFD of tests
      impacted more than 10%Delta by hemolysis were < 7% for LDH; < 5% for AST, folates
      and iron; and < 1% for the other analytes. Considering the ACL, HI were lower,
      giving % RFD substantially increased for many analytes, whereas only four
      analytes remain sensitive to hemolysis when considering RCV. CONCLUSION: This
      study proposes new HI based on different allowable limits, and can therefore
      serve as a starting point for future harmonization of hemolysis interference
      evaluation needed in routine laboratory practice.

PMID- 25608600
TI  - Extending the range of switchable-hydrophilicity solvents.
AB  - A switchable-hydrophilicity solvent (SHS) is a solvent that in one state forms a
      biphasic mixture with water but can be reversibly switched to another state that
      is miscible with water. All of the amine SHSs that we have reported previously
      lie within a particular basicity and hydrophilicity range (9.5 < pKaH < 11 and
      1.0 < log Kow < 2.5, respectively). We report an extension of this range by
      altering the pressure of CO2 as well as the water : SHS volume ratio used in the
      process. Increasing the pressure of CO2 and/or the water : amine volume ratio
      allows some amines with pKaH < 9.5 or log Kow > 2.5 to function as SHSs. 

PMID- 25608599
TI  - The utility of 18 F-FDG PET/CT for suspected recurrent breast cancer: impact and
      prognostic stratification.
AB  - BACKGROUND: The incremental value of 18FDG PET/CT in patients with breast cancer
      (BC) compared to conventional imaging (CI) in clinical practice is unclear. The
      aim of this study was to evaluate the management impact and prognostic value of
      18 F-FDG PET/CT in this setting. METHODS: Sixty-three patients who were referred
      to our institution for suspicion of BC relapse were retrospectively enrolled. All
      patients had been evaluated with CI and underwent PET/CT. At a median follow-up
      of 61 months, serial clinical, imaging and pathologic results were obtained to
      validate diagnostic findings. Overall Survival (OS) was estimated using Kaplan
      Meier methods and analyzed using the Cox proportional hazards regression models.
      RESULTS: Forty-two patients had a confirmed relapse with 37 (88%) positive on CI
      and 40 (95%) positive on PET/CT. When compared with CI, PET/CT had a higher
      negative predictive value (86% versus 54%) and positive predictive value (95%
      versus 70%). The management impact of PET/CT was high (change of treatment
      modality or intent) in 30 patients (48%) and medium (change in radiation
      treatment volume or dose fractionation) in 6 patients (9%). Thirty-nine patients
      (62%) died during follow-up. The PET/CT result was a highly significant predictor
      of OS (Hazard Ratio [95% Confidence Interval] =4.7 [2.0-10.9] for PET positive
      versus PET negative for a systemic recurrence; p = 0.0003). In a Cox multivariate
      analysis including other prognosis factors, PET/CT findings predicted survival (p
      = 0.005). In contrast, restaging by CI was not significant predictor of survival.
      CONCLUSION: Our study support the value of 18 F-FDG PET/CT in providing
      incremental information that influence patient management and refine prognostic
      stratification in the setting of suspected recurrent breast cancer.

PMID- 25608601
TI  - Single ion magnet behaviour in a two-dimensional network of dicyanamide-bridged
      cobalt(II) ions.
AB  - A novel two-dimensional coordination polymer of the formula [Co(dca)2(atz)2]n ()
      resulted from assembling trans-bis(2-amino-1,3,5-triazine)cobalt(ii) motifs by
      dicyanamide spacers. Variable-temperature dc and ac magnetic susceptibility
      measurements of show that the high-spin cobalt(ii) ions act as single ion magnets
      (SIMs). 

PMID- 25608602
TI  - Redundancy and metabolic function of the glutamine synthetase gene family in
      poplar.
AB  - BACKGROUND: Glutamine synthetase (GS; EC: 6.3.1.2, L-glutamate: ammonia ligase
      ADP-forming) is a key enzyme in ammonium assimilation and metabolism in higher
      plants. In poplar, the GS family is organized in 4 groups of duplicated genes, 3
      of which code for cytosolic GS isoforms (GS1.1, GS1.2 and GS1.3) and one group
      that codes for the choroplastic GS isoform (GS2). Our previous work suggested
      that GS duplicates may have been retained to increase the amount of enzyme in a
      particular cell type. RESULTS: The current study was conducted to test this
      hypothesis by developing a more comprehensive understanding of the molecular and
      biochemical characteristics of the poplar GS isoenzymes and by determinating
      their kinetic parameters. To obtain further insights into the function of the
      poplar GS genes, in situ hybridization and laser capture microdissections were
      conducted in different tissues, and the precise GS gene spatial expression
      patterns were determined in specific cell/tissue types of the leaves, stems and
      roots. The molecular and functional analysis of the poplar GS family and the
      precise localization of the corresponding mRNA in different cell types strongly
      suggest that the GS isoforms play non-redundant roles in poplar tree biology.
      Furthermore, our results support the proposal that a function of the duplicated
      genes in specific cell/tissue types is to increase the abundance of the enzymes.
      CONCLUSION: Taken together, our results reveal that there is no redundancy in the
      poplar GS family at the whole plant level but it exists in specific cell types
      where the two duplicated genes are expressed and their gene expression products
      have similar metabolic roles. Gene redundancy may contribute to the homeostasis
      of nitrogen metabolism in functions associated with changes in environmental
      conditions and developmental stages.

PMID- 25608603
TI  - Dynamic multidetector computed tomography findings of hepatocellular carcinoma of
      hepatitis B virus-positive and -negative patients.
AB  - BACKGROUND: The objective of this study was to retrospectively investigate and
      compare multidetector computed tomography findings of hepatocellular carcinoma
      (HCC) in hepatitis B virus (HBV)-positive and -negative patients. METHODS:
      Triphasic (arterial, portal venous, and delayed phases) dynamic multidetector
      computed tomography (CT) was performed in 83 patients with HCC, 48 of whom were
      HBV-positive. The diagnosis of HCC was established with typical CT imaging
      findings (68 patients) or histopathological evaluation (15 patients).
      Distribution of solitary, multiple, and diffuse HCC, portal/hepatic vein
      thrombosis, metastasis, and patients with high alpha-fetoprotein levels in the
      HBV-positive and -negative groups were compared using the Kolmogorov-Smirnov
      test. Lesion size, alpha-fetoprotein levels, arterial, portal, delayed
      enhancement, and washout of lesions were compared using the Student's t-test.
      RESULTS: Hypervascular tumors were observed in 72 (87%) patients, and
      hypovascular tumors were found in 11 (13%) patients. The mean alpha-fetoprotein
      value of HBV-positive patients with HCC was significantly higher than the mean
      alpha-fetoprotein value of HBV-negative patients (P < 0.05). Portal/hepatic vein
      thrombosis and metastasis were more frequently observed in HBV-positive patients
      (P < 0.05). The frequencies of solitary, multiple, and diffuse lesions in HBV
      positive and -negative patients were not significantly different (P > 0.05). The
      mean diameters, arterial, portal, and delayed phase attenuations, and washout of
      HCC were not significantly different (P > 0.05). CONCLUSIONS: Multidetector CT
      imaging findings of HCC in HBV-positive and -negative patients are alike.
      Portal/hepatic vein thrombosis and metastasis are more frequently observed in HBV
      positive patients. Alpha-fetoprotein levels are higher in HBV-positive patients.

PMID- 25608604
TI  - Preventing surgical disputes through early detection and intervention: a case
      control study in China.
AB  - BACKGROUND: Medical disputes have become a serious issue in China. A crisis
      cannot usually be predicted and managed through a cost-benefit strategy;
      therefore, researchers believe that prevention is better than containment and
      post-crisis resolution. This study aimed to identify solutions to prevent medical
      disputes in surgical cases through early warning and intervention of potential
      cases. METHODS: A case-control study was conducted to identify early detection
      indicators of medical disputes in the surgical treatment of liver cancer through
      Delphi consultation and logistic regression on the basis of which interventions
      were undertaken to prevent potential cases. RESULTS: The dispute detection model
      was composed of patient age (P = 0.08), frequency of hospitalization (P = 0.003),
      length of hospital stay (P < 0.001), terminal condition (P = 0.004), unplanned
      reoperation (P = 0.048), blood transfusion volume (P = 0.006), and arrearage (P <
      0.001). Risk management interventions through quality improvement and enhanced
      communication in cases with an abnormal performance indicator proved effective in
      practice. CONCLUSIONS: This study explored the use of an evidence-based medical
      risk management strategy for medical disputes that involved early detection and
      intervention and could potentially be adopted by hospitals to prevent medical
      disputes.

PMID- 25608605
TI  - Natural course of behavioral addictions: a 5-year longitudinal study.
AB  - BACKGROUND: Resolving the theoretical controversy on the labeling of an
      increasing number of excessive behaviors as behavioral addictions may also be
      facilitated by more empirical data on these behavioral problems. For instance, an
      essential issue to the classification of psychiatric disorders is information on
      their natural course. However, longitudinal research on the chronic vs. episodic
      nature of behavioral addictions is scarce. The aim of the present study,
      therefore, was to provide data on prevalence, substance use comorbidity, and five
      year trajectories of six excessive behaviors-namely exercising, sexual behavior,
      shopping, online chatting, video gaming, and eating. METHODS: Analyses were based
      on the data of the Quinte Longitudinal Study, where a cohort of 4,121 adults from
      Ontario, Canada was followed for 5 years (2006 to 2011). The response rate was
      21.3%, while retention rate was 93.9%. To assess the occurrence of each problem
      behavior, a single self-diagnostic question asked people whether their over
      involvement in the behavior had caused significant problems for them in the past
      12 months. To assess the severity of each problem behavior reported, the
      Behavioral Addiction Measure was administered. A mixed design ANOVA was used to
      investigate symptom trajectories over time for each problem behavior and whether
      these symptom trajectories varied as a function of sex. RESULTS: The large
      majority of people reported having problematic over-involvement for just one of
      these behaviors and just in a single time period. A main effect of time was found
      for each problem behavior, indicating a moderately strong decrease in symptom
      severity across time. The time x sex interaction was insignificant in each model
      indicating that the decreasing trend is similar for males and females. The data
      also showed that help seeking was very low in the case of excessive sexual
      behavior, shopping, online chatting, and video gaming but substantially more
      prevalent in the case of excessive eating and exercising. CONCLUSIONS: The
      present results indicate that self-identified excessive exercising, sexual
      behavior, shopping, online chatting, video gaming, and/or eating tend to be
      fairly transient for most people. This aspect of the results is inconsistent with
      conceptualizations of addictions as progressive in nature, unless treated.

PMID- 25608606
TI  - TNFalpha signalling primes chromatin for NF-kappaB binding and induces rapid and
      widespread nucleosome repositioning.
AB  - BACKGROUND: The rearrangement of nucleosomes along the DNA fiber profoundly
      affects gene expression, but little is known about how signalling reshapes the
      chromatin landscape, in three-dimensional space and over time, to allow
      establishment of new transcriptional programs. RESULTS: Using micrococcal
      nuclease treatment and high-throughput sequencing, we map genome-wide changes in
      nucleosome positioning in primary human endothelial cells stimulated with tumour
      necrosis factor alpha (TNFalpha) - a proinflammatory cytokine that signals
      through nuclear factor kappa-B (NF-kappaB). Within 10 min, nucleosomes reposition
      at regions both proximal and distal to NF-kappaB binding sites, before the
      transcription factor quantitatively binds thereon. Similarly, in long TNFalpha
      responsive genes, repositioning precedes transcription by pioneering elongating
      polymerases and appears to nucleate from intragenic enhancer clusters resembling
      super-enhancers. By 30 min, widespread repositioning throughout megabase pair
      long chromosomal segments, with consequential effects on three-dimensional
      structure (detected using chromosome conformation capture), is seen. CONCLUSIONS:
      Whilst nucleosome repositioning is viewed as a local phenomenon, our results
      point to effects occurring over multiple scales. Here, we present data in support
      of a TNFalpha-induced priming mechanism, mostly independent of NF-kappaB binding
      and/or elongating RNA polymerases, leading to a plastic network of interactions
      that affects DNA accessibility over large domains.

PMID- 25608607
TI  - Predictors of thromboprophylaxis in hospitalised medical patients. Explicit
      ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in
      SwitzErland (ESTIMATE).
AB  - Both, underuse and overuse of thromboprophylaxis in hospitalised medical patients
      is common. We aimed to explore clinical factors associated with the use of
      pharmacological or mechanical thromboprophylaxis in acutely ill medical patients
      at high (Geneva Risk Score >= 3 points) vs low (Geneva Risk Score < 3 points)
      risk of venous thromboembolism. Overall, 1,478 hospitalised medical patients from
      eight large Swiss hospitals were enrolled in the prospective Explicit ASsessment
      of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland
      (ESTIMATE) cohort study. The study is registered on ClinicalTrials.gov, number
      NCT01277536. Thromboprophylaxis increased stepwise with increasing Geneva Risk
      Score (p< 0.001). Among the 962 high-risk patients, 366 (38 %) received no
      thromboprophylaxis; cancer-associated thrombocytopenia (OR 4.78, 95 % CI 2.75
      8.31, p< 0.001), active bleeding on admission (OR 2.88, 95 % CI 1.69-4.92, p<
      0.001), and thrombocytopenia without cancer (OR 2.54, 95 % CI 1.31-4.95, p=0.006)
      were independently associated with the absence of prophylaxis. The use of
      thromboprophylaxis declined with increasing severity of thrombocytopenia
      (p=0.001). Among the 516 low-risk patients, 245 (48 %) received
      thromboprophylaxis; none of the investigated clinical factors predicted its use.
      In conclusion, in acutely ill medical patients, bleeding and thrombocytopenia
      were the most important factors for the absence of thromboprophylaxis among high
      risk patients. The use of thromboprophylaxis among low-risk patients was
      inconsistent, without clearly identifiable predictors, and should be addressed in
      further research.

PMID- 25608608
TI  - Assessment of nutritional status and health-related quality of life before and
      after liver transplantation.
AB  - BACKGROUND: Patients with chronic liver disease frequently suffer from
      malnutrition, together with a decline in their health-related quality of life.
      This study was carried out with the aim of evaluating the nutritional status,
      complications of medical and surgical care, anxiety, health-related quality of
      life and dependence level on basic and instrumental activities of daily living in
      pre- and post-liver transplant patients. METHODS/DESIGN: A prospective
      observational study with follow-up of patients on the waiting list for liver
      transplants who subsequently received a transplant at the University Hospital
      Complex in A Coruna during the period 2012-2014 (n = 110). All the patients will
      be followed-up for a maximum of 6 months. For survivors, assessments will be re
      evaluated at one, three and six months post- transplant. Informed consent of the
      patient and ethical review board approval was obtained (Code: 2010/081 and
      2010/082). The following variables will be studied: socio-demographic data,
      reason for the transplant, comorbidity (Charlson Score), analytical parameters,
      time on transplant waiting list and post-transplant complications. A trained
      nurse will evaluate the following for each patient: nutritional indices,
      anthropometric variables and handgrip strength. Validated questionnaires will be
      used to determine the patients' nutritional status (Subjective Global
      Assessment), anxiety (STAI questionnaire), Health-Related Quality of Life (LDQoL
      1.0 questionnaire), dependence (Barthel Index and Lawton-Brody Scale), nursing
      diagnoses (NANDA) and post-transplant quality indicators. Multiple
      linear/logistic regression models will be used to identify variables associated
      with the events of interest. Changes in nutritional status, quality of life and
      dependence over time will be analysed with linear mixed-effects regression
      models. Actuarial survival analysis using Kaplan-Meier curves, Cox regression and
      competitive risk will be performed Concordance between the different scores that
      assess nutritional status and interobserver agreement regarding nursing diagnoses
      will be studied using the statistical Kappa index and Bland Altman method.
      DISCUSSION: The risk of malnutrition can be considered as a possible prognostic
      factor in transplant outcomes, associated with anxiety, health-related quality of
      life and dependence. For this reason we consider interesting to perform a
      prospective follow-up study of patients who require a transplant to survive,
      studying their nutritional status and health-related quality of life.

PMID- 25608609
TI  - Cost to households in treating maternal complications in northern Ghana: a cross
      sectional study.
AB  - BACKGROUND: The cost of treating maternal complications has serious economic
      consequences to households and can hinder the utilization of maternal health care
      services at the health facilities. This study estimated the cost of maternal
      complications to women and their households in the Kassena-Nankana district of
      northern Ghana. METHODS: We carried out a cross-sectional study between February
      and April 2014 in the Kassena-Nankana district. Out of a total of 296 women who
      were referred to the hospital for maternal complications from the health centre
      level, sixty of them were involved in the study. Socio-demographic data of
      respondents as well as direct and indirect costs involved in the management of
      the complications at the hospital were collected from the patient's perspective.
      Analysis was performed using STATA 11. RESULTS: Out of the 60 respondents, 60%
      (36) of them suffered complications due to prolonged labour, 17% (10) due to
      severe abdominal pain, 10% (6) due to anaemia/malaria and 7% (4) due to pre
      eclampsia. Most of the women who had complications were primiparous and were
      between 21-25 years old. Transportation cost accounted for the largest cost,
      representing 32% of total cost of treatment. The median direct medical cost was
      US$8.68 per treatment, representing 44% of the total cost of treatment. Indirect
      costs accounted for the largest proportion of total cost (79%). Overall, the
      median expenditure by households on both direct and indirect costs per
      complication was US$32.03. Disaggregating costs by type of complication, costs
      ranged from a median of US$58.33 for pre-eclampsia to US$6.84 for haemorrrhage.
      The median number of days spent in the hospital was 2 days - five days for pre
      eclampsia. About 33% (6) of households spent more than 5% of annual household
      expenditure and therefore faced catastrophic payments. CONCLUSION: Although
      maternal health services are free in Ghana, women still incur substantial costs
      when complications occur and face the risk of incurring catastrophic health
      expenditure.

PMID- 25608611
TI  - Sexual dysfunction and sexual quality of life among the physically challenged in
      the Kumasi metropolis, Ghana.
AB  - BACKGROUND: Despite the fact that the physically disabled have difficulties in
      many aspects of their lives, including sexuality, society often ignores these
      needs or assume that they have no such needs. This cross-sectional study
      therefore seeks to determine the prevalence of sexual dysfunction (SD) and its
      impact on the quality of life among persons with physical disability residing in
      the Kumasi metropolis, Ghana. METHOD: This study was conducted among 235 persons
      with physical disability dwelling in communities within the Kumasi metropolis,
      Ghana between September 2011 and April 2012. All participants were evaluated by
      using a semi-structured questionnaire, the Golombok Rust Inventory of Sexual
      Satisfaction (GRISS) questionnaire and the Sexual Quality of Life questionnaire
      (SQoL). Self-designed semi-structured questionnaire was also administered to each
      consented study participant for socio-demographic information. RESULTS: The
      response rates were 72% and 63.6% for male and female respectively. The age range
      of the male was 19-74 years with 61.1% being married whilst the age range of the
      female was 20-66 years with 54.3% being married. 30% and 7.1% of the male and
      female respectively consumed alcohol beverage. The mean Sexual quality of life
      (SQoL) score was slightly higher in the females (57.7 +/- 15.8), ranging from
      25.6 to 97.8. Univariate analysis of the male data showed that the only
      significant factor that tends to increase the male SD was alcohol (OR: 24.6; CI:
      1.4 - 14.9; p = 0.0071). The prevalence of SD was higher among the female
      populace (65.7%) compared to the 64.4% for the male populace though very closely
      comparable. Except for non-communication (NC) and anorgasmia (impotence in
      males), all other areas of difficulty had higher percentages in males than
      females. CONCLUSION: The prevalence of sexual dysfunction among the physically
      challenged is comparable to prevalence rates in the able male and female
      population. This could impact significantly on their self-esteem and quality of
      life via avoidance, impotence and vaginismus thereby causing emotional distress
      leading to relationship problems. Alcohol increases the risk of developing SD by
      five-fold in physically challenged men.

PMID- 25608610
TI  - The population genetics of wild chimpanzees in Cameroon and Nigeria suggests a
      positive role for selection in the evolution of chimpanzee subspecies.
AB  - BACKGROUND: Chimpanzees (Pan troglodytes) can be divided into four subspecies.
      Substantial phylogenetic evidence suggests that these subspecies can be grouped
      into two distinct lineages: a western African group that includes P. t. verus and
      P. t. ellioti and a central/eastern African group that includes P. t. troglodytes
      and P. t. schweinfurthii. The geographic division of these two lineages occurs in
      Cameroon, where the rages of P. t. ellioti and P. t. troglodytes appear to
      converge at the Sanaga River. Remarkably, few population genetic studies have
      included wild chimpanzees from this region. RESULTS: We analyzed microsatellite
      genotypes of 187 wild, unrelated chimpanzees, and mitochondrial control region
      sequencing data from 604 chimpanzees. We found that chimpanzees in Cameroon and
      eastern Nigeria comprise at least two, and likely three populations. Both the
      mtDNA and microsatellite data suggest that there is a primary separation of P. t.
      troglodytes in southern Cameroon from P. t. ellioti north and west of the Sanaga
      River. These two populations split ~200-250 thousand years ago (kya), but have
      exchanged one migrant per generation since separating. In addition, P. t. ellioti
      consists of two populations that split from one another ~4 kya. One population is
      located in the rainforests of western Cameroon and eastern Nigeria, whereas the
      second population appears to be confined to a savannah-woodland mosaic in central
      Cameroon. CONCLUSIONS: Our findings suggest that there are as many as three
      genetically distinct populations of chimpanzees in Cameroon and eastern Nigeria.
      P. t. troglodytes in southern Cameroon comprises one population that is separated
      from two populations of P. t. ellioti in western and central Cameroon,
      respectively. P. t. ellioti and P. t. troglodytes appear to be characterized by a
      pattern of isolation-with-migration, and thus, we propose that neutral processes
      alone can not explain the differentiation of P. t. ellioti and P. t. troglodytes.

PMID- 25608612
TI  - Some simple nosocomial disease transmission models.
AB  - The SARS epidemic of 2002-2003 drew attention to nosocomial disease transmission
      as many of the disease cases were transmitted through hospital staff and
      visitors. Various types of model have been proposed to describe this, including
      metapopulation models. We formulate and analyze a simple compartmental model with
      heterogeneous mixing to describe nosocomial transmission and determine the
      reproduction number and final size relation. 

PMID- 25608613
TI  - The Omp85-type outer membrane protein p36 of Arabidopsis thaliana evolved by
      recent gene duplication.
AB  - Proteins of the Omp85 family are involved in the insertion of beta-barrel shaped
      outer membrane proteins in bacteria and mitochondria, and-at least-in the
      transfer of preproteins across the chloroplast outer envelope. In general these
      proteins consist of up to five N-terminal "polypeptide transport associated"
      (POTRA) domains and a C-terminal, membrane embedded beta-barrel domain. In
      Arabidopsis thaliana two plastidic gene families coding for Omp85-like proteins
      exist, namely the Toc75-III and the Toc75-V/Oep80 sub-family. The latter is
      composed of three genes, of which two do not contain POTRA domains. These are
      annotated as P39 and P36. However, P36 resulted from a very recent gene
      duplication of P39 and appears to be specific to Arabidopsis thaliana.
      Furthermore, we show that P39 is specifically expressed in vein tissues, while
      P36 is expressed at early and late developmental stages. T-DNA insertion in P36
      causes a mild phenotype with reduced starch accumulation in chloroplasts of
      sepals pointing towards a yet to be described plastid function.

PMID- 25608615
TI  - Reducing radiation exposure during invasive coronary angiography and percutaneous
      coronary interventions implementing a simple four-step protocol.
AB  - BACKGROUND: With an increasing number of complex and repeated percutaneous
      coronary interventions (PCI), radiation-induced hazards for patients and
      operators remain an important issue in fluoroscopy-guided procedures. Our
      objective was to evaluate radiation exposure during coronary angiographic
      procedures and assess the efficacy of a four-step program to reduce radiation
      exposure during coronary angiography (CAG) and PCI. METHODS AND RESULTS: A
      retrospective single-center analysis was performed in patients undergoing CAG or
      PCI in the first 6 months of 2012 vs. the first 6 months of 2014 (n = 3,107
      procedures). During 2013, a four-step protocol was established in our hospital.
      It contained measures to reduce radiation exposure, including a frame rate
      reduction from 15 to 7.5 frames per second, the use of fluoroscopy storage,
      strict use of beam collimation, and repeat training on radiation safety. After
      adjustment for confounding variables, a dose-area product (DAP) reduction of
      54.2% was observed subsequent to implementation of the four-step protocol.
      Independent predictors of DAP were age [odds ratio (OR) 1.01], body surface area
      (OR 5.47), prior coronary artery bypass grafting (OR 1.44), radial access (OR
      1.16), PCI (OR 2.36), female gender (OR 0.91), and the implementation of the four
      step program (OR 0.46). CONCLUSION: A simple four-step protocol led to a
      significant reduction in radiation exposure in diagnostic and interventional
      coronary procedures without significant drawbacks in image quality. Hence,
      radiation safety programs are of paramount importance and should be established
      to improve patient and operator safety with regard to radiation-induced hazards.

PMID- 25608614
TI  - Gender differences in clinical characteristics and outcome of acute heart failure
      in sub-Saharan Africa: results of the THESUS-HF study.
AB  - BACKGROUND: The impact of gender on the clinical characteristics, risk factors,
      co-morbidities, etiology, treatment and outcome of acute heart failure in sub
      Saharan Africa has not been described before. The aim of this study was to
      evaluate the sex differences in acute heart failure in sub-Saharan Africa using
      the data from The sub-Saharan Africa Survey of Heart Failure (THESUS-HF). METHODS
      AND RESULTS: 1,006 subjects were recruited into this prospective multicenter,
      international observational heart failure survey. The mean age of total
      population was 52.4 years (54.0 years for men and 50.7 years for women). The men
      were significantly older (p = 0.0045). Men also presented in poorer NYHA
      functional class (III and IV), p = 0.0364). Cigarette smoking and high blood
      pressure were significantly commoner in men (17.3 vs. 2.6% and 60.0 vs. 51.0%
      respectively). On the other hand, atrial fibrillation and valvular heart disease
      were significantly more frequent in women. The mean hemoglobin concentration was
      lower in women compared to men (11.7 vs. 12.6 g/dl, p <= 0.0001), while the blood
      urea and creatinine levels were higher in men (p < 0.0001). LV systolic
      dysfunctional was also seen more in men. Men also had higher E/A ratio indicating
      higher LV filling pressure. Outcomes were similar in both sexes. CONCLUSIONS:
      Although the outcome of patients admitted for AHF in sub-Saharan regions is
      similar in men and women, some gender differences are apparent suggesting that in
      men more emphasis should be put on modifiable life risk factors, while in women
      prevention of rheumatic heart diseases and improved nutrition should be addressed
      vigorously.

PMID- 25608616
TI  - Mediastinal staging in Non-Small-Cell Lung Carcinoma: computed tomography versus
      F-18-fluorodeoxyglucose positron-emission tomography and computed tomography.
AB  - BACKGROUND: After the diagnosis Non-Small-Cell Lung Carcinoma (NSCLC) has been
      established, consideration must turn toward the stage of disease, because this
      will impact directly on management and prognosis. Staging is used to predict
      survival and to guide the patient toward the most appropriate treatment regimen
      or clinical trial. Distinguishing malignant involvement of the mediastinal lymph
      nodes (N2 or N3) from the hilar lymph nodes, or no lymph nodes (N0 or N1) is
      critical, because malignant involvement of N2 or N3 lymph nodes usually indicates
      non-surgically resectable disease. The purpose of this study was to examine and
      compare CT versus integrated F18-FDG PET/low dose CT (FDG PET/CT) for mediastinal
      staging in NSCLC, and the desire was to safely distinguish between malignant and
      benign lesions without the need for invasive procedures. All results were
      controlled for reproducibility. METHODS: 114 participants with NSCLC were
      included in a prospective cohort study. Blinded CT and FDG PET/CT images were
      reviewed. The participants' mediastinums were staged based on lymph node sizes
      (CT), or on FDG uptake (FDG PET/CT). Reference standard was tissue sampling.
      RESULTS: We found that there was no measureable difference between CT and FDG
      PET/CT mediastinal staging results; overall two-thirds of the participants in the
      study were correctly staged, and almost one-third of the participants were
      falsely staged. CONCLUSION: Neither CT nor FDG PET/CT could obviate the need for
      further invasive staging prior to thoracotomy in patients with NSCLC; for that
      purpose, the results of both modalities were too meagre. Therefore, these
      patients still depend on invasive staging methods. In our study, invasive staging
      was accomplished by mediastinoscopy. However, today this is increasingly replaced
      by EBUS or EUS.

PMID- 25608617
TI  - A simultaneous extraction method for organophosphate, pyrethroid, and
      neonicotinoid insecticides in aqueous samples.
AB  - A method was developed for the extraction and analysis of 2 organophosphate, 8
      pyrethroid, and 5 neonicotinoid insecticides from the same water sample. A salted
      liquid-liquid extraction (LLE) was optimized with a solid-phase extraction (SPE)
      step that separated the organophosphates (OPs) and pyrethroids from the
      neonicotinoids. Factors that were optimized included volume of solvent and amount
      of salt used in the LLE, homogenization time for the LLE, and type and volume of
      eluting solvent used for the SPE. The OPs and pyrethroids were quantified using
      gas chromatography-mass spectrometry, and the neonicotinoids were quantified
      using liquid chromatography-diode array detector. Results showed that the
      optimized method was accurate, precise, reproducible, and robust; recoveries in
      river water spiked with 100 ng L(-1) of each of the insecticides were all between
      86 and 114 % with RSDs between 2 and 8 %. The method was also sensitive with
      method detection limits ranging from 0.1 to 27.2 ng L(-1) depending on compounds
      and matrices. The optimized method was thus appropriate for the simultaneous
      extraction of 15 widely applied insecticides from three different classes and was
      shown to provide valuable information on their environmental fate from field
      collected aqueous samples. 

PMID- 25608619
TI  - microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual
      pathways in hepatocellular carcinoma.
AB  - Growing evidence indicates that miR-146a is involved in carcinogenesis and tumor
      progression in several human malignancies. However, the molecular details
      underlying miR-146a mediated regulation of its target genes and its precise
      biological function in cancer, especially in hepatocellular carcinoma (HCC)
      remains unclear. METHODS: The expression levels of genes including miR-146a, APC,
      VEGF and HAb18G were examined in HCC cell lines and patient specimens were
      compared with control levels using quantitative reverse transcription-PCR. The
      functions of miR-146a and HAb18G in migration/invasion and liver metastasis
      formation were determined by transwell and spleen injection assays, respectively.
      miR-146a related genes were determined by PCR array. The potential regulatory
      targets of miR-146a were determined by bioinformatics and prediction tools,
      correlation with target protein expression, and luciferase reporter assay. DNA
      methylation status of miR-146a promoter were performed by PCR analysis of
      bisulfite-modified genomic DNA. RESULTS: We demonstrated that miR-146a expression
      was markedly downregulated in hepatoma cells and hepatoma tissues compared to
      immortalized normal liver epithelial cells and normal hepatic tissues. DNA
      methylation of miR-146a promoter correlated with its downexpression and with
      liver cancer metastasis. The restoration of miR-146a dramatically suppressed HCC
      cell invasion and metastasis by repressing VEGF expression through upregulating
      APC, which inhibits beta-catenin accumulation in nucleus, and downregulating NF
      kappaB p65 by targeting HAb18G. In human HCC, miR-146a expression was negative
      correlated with increased HAb18G, VEGF, NF-kappaB p65 and beneficial prognosis.
      CONCLUSION: This study identified a novel target of miR-146a and defined miR-146a
      as a crucial tumor suppressor in human HCC that acts through multiple pathways
      and mechanisms to suppress HCC invasion or metastasis.

PMID- 25608620
TI  - Clinicopathological and treatment analysis of 13 extragastrointestinal stromal
      tumors of mesentery and retroperitoneum.
AB  - BACKGROUND: Extragastrointestinal stromal tumors (EGISTs) are extremely rare
      mesenchymal tumors histologically and immunophenotypically similar to GI stromal
      tumors (GISTs). The aim of this study was to analyze the clinicopathological
      factors and treatment outcome in 13 patients with EGISTs treated at a tertiary
      care center. METHODS: Of 109 patients with GISTs treated at our center between
      April 2002 and December 2012, 13 patients with EGISTs were analyzed for
      clinicopathological factors and treatment outcome. RESULTS: Mean age was 45.8
      (range 30-61) years, and females constituted 62% with a male:female ratio of
      0.6:1. The most common tumor sites were mesentery in 10 patients and
      retroperitoneum in 3 patients. Mean tumor size was 11.7 (range 5-18) cm. Four
      (31%) patients were metastatic at presentation, the most common site of
      metastases being the liver in 3 (75%) patients. Lymph node enlargement was seen
      in 2 patients. Surgery was performed in 8 (62%) patients, 7 with localized
      disease, and 1 with metastatic disease. R0 resection was achieved in 3 (38%)
      patients. Five (71%) patients were considered as high-risk. Recurrences were seen
      in 3 patients (patient 3, 5 and 13) with localized disease after surgical
      resection, at 18, 7 and 137 months, respectively. At the last follow up, 7
      patients were alive and 6 died of disease progression. The median overall
      survival was 34 (7-148) months. CONCLUSIONS: EGISTs present at a younger age in
      the developing than in the developed countries. Females are more commonly
      affected than males. Lymph node metastases may be commonly present.

PMID- 25608621
TI  - The first pathogenic Yersinia enterocolitica bioserotype 4/O:3 strain isolated
      from a hunted wild boar (Sus scrofa) in Poland.
AB  - The objective of this study was to identify the bioserotypes and virulence
      markers of Yersinia enterocolitica strains isolated from wild boars in Poland.
      Bacteriological examination of 302 rectal swabs from 151 wild boars resulted in
      the isolation of 40 Y. enterocolitica strains. The majority of the examined
      strains (n = 30), belonged to bioserotype 1A/NI. The presence of individual Y.
      enterocolitica strains belonging to bioserotypes 1B/NI (3), 1A/O:8 (2), 1A/O:27
      (2), 2/NI (1), 2/O:9 (1) and 4/O:3 (1) was also demonstrated. Amplicons
      corresponding to ail and ystA genes were observed only in one Y. enterocolitica
      strain--bioserotype 4/O:3. The ail and ystB gene amplicons were noted in 11 Y.
      enterocolitica biotype 1A strains, although single amplicons of ystB gene were
      found in 28 of the tested samples. In four out of eight cases when two Y.
      enterocolitica strains were isolated from the same animal, the strains differed
      in biotype, serotype or virulence markers. The European population of wild boars
      continues to grow and spread to new areas, therefore, wild boars harbouring
      potentially pathogenic Y. enterocolitica 4/O:3 strains pose a challenge to public
      health.

PMID- 25608622
TI  - Questionnaire study and postmortem findings in backyard chicken flocks in
      Finland.
AB  - BACKGROUND: Although modern commercial poultry production today is based on large
      farms and intensive husbandry, keeping backyard poultry has regained popularity
      in industrialized countries. However, the health status of backyard flocks is
      still relatively poorly documented. A questionnaire was sent to the owners of 376
      backyard poultry flocks (<500 birds) in order to study health management
      procedures and characterize backyard poultry populations in Finland. Information
      was also collected on the postmortem findings from non-commercial flocks using
      necropsy data from the Finnish Food Safety Authority (Evira). RESULTS: Backyard
      flocks in Finland are small in size (<50 birds), comprising mainly chickens.
      Based on the results of the questionnaire, the health of such flocks is good,
      mortality low and vaccinations are not commonly used. Most of the flocks were
      registered in the national poultry register. The standard biosecurity practices
      are not generally applied and contact with wild birds, pets and farm animals is
      frequent, which can make the flocks more prone to infectious diseases. We
      conducted an 11-year retrospective study of the postmortem necropsy findings of
      the Evira in order to document the diseases, which caused mortality in backyard
      chickens in Finland. Necropsy was performed on a total of 132 non-commercial
      laying hens during 2000 - 2011. The most common postmortem findings were Marek's
      disease (27%) and colibacillosis (17%). CONCLUSIONS: This study is the first to
      report data on characteristics of and management practices for backyard chicken
      flocks in Finland. Close connections with commercial flocks are rare and farms
      are usually distantly located suggesting that the risk that these backyard flocks
      pose to commercial poultry is low.

PMID- 25608623
TI  - Morphological factors differentiating between early lung adenocarcinomas
      appearing as pure ground-glass nodules measuring <=10 mm on thin-section computed
      tomography.
AB  - BACKGROUND: We aimed to compare the morphological features of pure ground-glass
      nodules (GGNs; diameter, <=10 mm) on thin-section computed tomography (TSCT) with
      their histopathological results in order to identify TSCT features
      differentiating between atypical adenomatous hyperplasia (AAH), adenocarcinoma in
      situ (AIS) and minimally invasive adenocarcinoma (MIA). METHODS: Between January
      and December 2013, 205 pure GGNs with a diameter <=10 mm on TSCT were
      pathologically confirmed as AAH (40), AIS (95) or MIA (70) lesions. The patients'
      age and sex were recorded. The morphological features were evaluated, and maximum
      diameter and mean CT value were measured for each nodule. F test, Pearson chi2
      test, Fisher exact test and multinomial logistic regression analysis were used to
      identify factors differentiating between AAH, AIS and MIA. Receiver operating
      characteristic (ROC) curve analysis was performed for maximum diameter and mean
      CT value. RESULTS: F test, Pearson chi2 test and Fisher exact test revealed that
      maximum diameter (P <0.00001), mean CT value (P =0.005), type of interface (P
      =0.005) and presence of air bronchograms (P =0.02, n =44) significantly differed
      among the AAH, AIS and MIA groups. Multinomial logistic regression analysis
      showed that maximum diameter >=6.5 mm, a well-defined and coarse interface
      indicated AIS or MIA rather than AAH; air bronchograms differentiated MIA from
      AAH; but these parameters did not differentiate between AIS and MIA. A mean CT
      value less than -520 HU indicated AAH or AIS rather than MIA, but did not
      differentiate between AAH and AIS. CONCLUSIONS: In the case of pure GGNs
      measuring <=10 mm, a maximum diameter >=6.5 mm, a well-defined and coarse
      interface indicate AIS or MIA rather than AAH; an air bronchogram can
      differentiate MIA from AAH. A mean CT value less than -520 HU indicates AAH or
      AIS rather than MIA.

PMID- 25608624
TI  - The supplementary therapeutic DMARD role of low-dose glucocorticoids in
      rheumatoid arthritis.
AB  - The management of rheumatoid arthritis (RA) is primarily based on the use of
      disease-modifying antirheumatic drugs (DMARDs), mainly comprising synthetic
      chemical compounds (that is, methotrexate or leflunomide) and biological agents
      (tumor necrosis factor inhibitors or abatacept). On the other hand,
      glucocorticoids (GCs), used for decades in the treatment of RA, are effective in
      relieving signs and symptoms of the disease, but also interfere with radiographic
      progression, either as monotherapy or in combination with conventional synthetic
      DMARDs. GCs exert most of their biological effects through a genomic action,
      using the cytosolic GC receptor and then interacting with the target genes within
      target cells that can result in increased expression of regulatory--including
      anti-inflammatory--proteins (transactivation) or decreased production of
      proinflammatory proteins (transrepression). An inadequate secretion of GCs from
      the adrenal gland, in relation to stress and inflammation, seems to play an
      important role in the pathogenesis and disease progression of RA. At present
      there is clear evidence that GC therapy, especially long-term low-dose treatment,
      slows radiographic progression by at least 50% when given to patients with early
      RA, hence satisfying the conventional definition of a DMARD. In addition, long
      term follow-up studies suggest that RA treatment strategies which include GC
      therapy may favorably alter the disease course even after their discontinuation.
      Finally, a low-dose, modified night-release formulation of prednisone, although
      administered in the evening (replacement therapy), has been developed to
      counteract the circadian (night) rise in proinflammatory cytokine levels that
      contributes to disease activity, and might represent the way to further optimize
      the DMARD activity exerted by GCs in RA.

PMID- 25608627
TI  - [Hepatitis E virus: opinions of the Working Group of the Federal Ministry of
      Health Blood].

PMID- 25608625
TI  - Pre-gestational vs gestational exposure to maternal obesity differentially
      programs the offspring in mice.
AB  - AIMS/HYPOTHESIS: Maternal obesity is associated with an increased risk of obesity
      and impaired glucose homeostasis in offspring. However, it is not known whether a
      gestational or pre-gestational exposure confers similar risks, and if so, what
      the underlying mechanisms are. METHODS: We used reciprocal two-cell embryo
      transfers between mice fed either a control or high-fat diet (HFD) starting at
      the time of weaning. Gene expression in placenta was assessed by microarray
      analyses. RESULTS: A pre-gestational exposure to a maternal HFD (HFD/control)
      impaired fetal and placental growth despite a normal gestational milieu.
      Expression of imprinted genes and genes regulating vasculogenesis and lipid
      metabolism was markedly altered in placenta of HFD/control. An exposure to an HFD
      (control/HFD) only during gestation also resulted in fetal growth restriction and
      decreased placental weight. Interestingly, only a gestational exposure to an HFD
      (control/HFD) resulted in obesity and impaired glucose tolerance in adulthood.
      CONCLUSIONS/INTERPRETATION: An HFD during pregnancy has profound consequences for
      the offspring later in life. Our data demonstrate that the mechanism underlying
      this phenomenon is not related to placental dysfunction, intrauterine growth
      restriction or postnatal weight gain, but rather an inability of the progeny to
      adapt to the abnormal gestational milieu of an HFD. Thus, the ability to adapt to
      an adverse intrauterine environment is conferred prior to pregnancy and it is
      possible that the effects of a maternal HFD may be transmitted to subsequent
      generations.

PMID- 25608626
TI  - Magnification endoscopy in esophageal squamous cell carcinoma: a review of the
      intrapapillary capillary loop classification.
AB  - Recent developments in image-enhancement technology have enabled clear
      visualization of the microvascular structure of the esophageal mucosa. In
      particular, intrapapillary capillary loops (IPCLs) are observed as brown loops on
      magnification endoscopy with narrow-band imaging (NBI). IPCLs demonstrate
      characteristic morphological changes according to the structural irregularity of
      esophageal epithelium and cancer infiltration, summarized in the IPCL
      classification. In this review, the process from the first endoscopic description
      of IPCLs to the eventual development of the IPCL classification is described and
      discussed, particularly focusing on early stage squamous cell carcinoma of the
      esophagus.

PMID- 25608628
TI  - Don't Forget the Doctor: Gastroenterologists' Preferences on the Development of
      mHealth Tools for Inflammatory Bowel Disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) encompasses a number of disorders of
      the gastrointestinal tract. Treatment for IBD is lifelong and complex, and the
      majority of IBD patients seek information on the Internet. However, research has
      found existing digital resources to be of questionable quality and that patients
      find content lacking. Gastroenterologists are frontline sources of information
      for North American IBD patients, but their opinions and preferences for digital
      content, design, and utility have not been investigated. The purpose of this
      study is to systematically explore gastroenterologists' perceptions of, and
      design preferences for, mHealth tools. OBJECTIVE: Our goal was to critically
      assess these issues and elicit expert feedback by seeking consensus with Canadian
      gastroenterologists. METHODS: Using a qualitative approach, a closed meeting with
      7 gastroenterologists was audio recorded and field notes taken. To synthesize
      results, an anonymous questionnaire was collected at the end of the session.
      Participant-led discussion themes included methodological approaches to non
      adherence, concordance, patient-centricity, and attributes of digital tools that
      would be actively supported and promoted. RESULTS: Survey results indicated that
      4 of the 7 gastroenterologists had experienced patients bringing digital
      resources to a visit, but 5 found digital patient resources to be inaccurate or
      irrelevant. All participants agreed that digital tools were of increasing
      importance and could be leveraged to aid in consultations and save time. When
      asked to assess digital attributes that they would be confident to refer patients
      to, all seven indicated that the inclusion of evidence-based facts were of
      greatest importance. Patient peer-support networks were deemed an asset but only
      if closely monitored by experts. When asked about interventions, nearly all (6/7)
      preferred tools that addressed a mix of compliance and concordance, and only one
      supported the development of tools that focused on compliance. Participants
      confirmed that they would actively refer patients and other physicians to digital
      resources. However, while a number of digital IBD tools exist,
      gastroenterologists would be reluctant to endorse them. CONCLUSIONS:
      Gastroenterologists appear eager to use digital resources that they believe
      benefit the physician-patient relationship, but despite the trend of patient
      centric tools that focus on concordance (shared decision making and enlightened
      communication between patients and their health care providers), they would
      prefer digital tools that highlight compliance (patient following orders). This
      concordance gap highlights an issue of disparity in digital health: patients may
      not use tools that physicians promote, and physicians may not endorse tools that
      patients will use. Further research investigating the concordance gap, and
      tensions between physician preferences and patient needs, is required.

PMID- 25608629
TI  - Microalgae lipid characterization.
AB  - To meet the growing interest of utilizing microalgae biomass in the production of
      biofuels and nutraceutical and pharmaceutical lipids, we need suitable analytical
      methods and a comprehensive database for their lipid components. The objective of
      the present work was to demonstrate methodology and provide data on fatty acid
      composition, lipid class content and composition, characteristics of the
      unsaponifiables, and type of chlorophylls of five microalgae. Microalgae lipids
      were fractionated into TAG, FFA, and polar lipids using TLC, and the composition
      of fatty acids in total lipids and in each lipid class, hydrocarbons, and sterols
      were determined by GC-MS. Glyco- and phospholipids were profiled by LC/ESI-MS.
      Chlorophylls and their related metabolites were qualified by LC/APCI-MS. The
      melting and crystallization profiles of microalgae total lipids and their esters
      were analyzed by DSC to evaluate their potential biofuel applications.
      Significant differences and complexities of lipid composition among the algae
      tested were observed. The compositional information is valuable for strain
      selection, downstream biomass fractionation, and utilization. 

PMID- 25608630
TI  - Atomic-level study of the effects of O4 molecules on the structural properties of
      protofibrillar Abeta trimer: beta-sheet stabilization, salt bridge protection,
      and binding mechanism.
AB  - Alzheimer's disease (AD) is associated with the aggregation of amyloid-beta
      (Abeta) peptides into toxic prefibrillar aggregates. Recent experiments reported
      that small organic molecule O4 decreases the concentration of toxic oligomers by
      promoting fibrillation and thus reduces Abeta toxicity. However, the atomic-level
      details of O4-Abeta-oligomer interaction are largely unknown. In this work, we
      studied the structural stability of the fibrillike Abeta(17-42) trimer by
      performing atomistic molecular dynamics simulations of 1.5 MUs in total on the
      trimer with and without O4. We found that the Abeta(17-42) trimer is unstable
      without O4, whereas its structural stability is greatly enhanced with O4. Four
      binding sites were found around residues F20, S26, and M35, namely the central
      hydrophobic core (CHC) site, the turn site, and two hydrophobic-groove sites. The
      two hydrophobic grooves near M35 facilitate O4 to bind through hydrophobic
      interaction and geometry match. The binding of O4 at the CHC site is mostly
      stabilized by hydrophobic and pi-pi stacking interactions. Hydrogen-bonding
      interaction between O4 and S26 plays a role in the binding of O4 to the turn
      site. Our work reveals the detailed stabilization mechanism of protofibrillar
      Abeta oligomers by O4 and may provide novel insight into the development of drug
      candidates against AD. 

PMID- 25608631
TI  - Untreated masked hypertension and carotid atherosclerosis: a meta-analysis.
AB  - AIM: Masked hypertension (MH) is recognized as a clinical entity with an
      unfavorable cardiovascular prognosis; a limited number of reports, however,
      investigated the impact of this condition on subclinical vascular damage. We
      performed a meta-analysis aimed at evaluating the association of MH with
      subclinical carotid atherosclerosis in initially untreated subjects. DESIGN:
      Studies were identified by the following search terms: "masked hypertension",
      "isolated clinic normotension", "white coat normotension", "carotid artery",
      "carotid atherosclerosis", "carotid intima-media thickness", "carotid damage" and
      "carotid thickening". Full articles published in English language reporting data
      from studies performed in untreated adult individuals were considered. RESULTS:
      Overall, 2752 untreated subjects (1039 normotensive, 497 MH and 766 hypertensive
      individuals) of both genders were included in five studies (sample size range 18
      222 for MH participants). Common carotid intima-media thickness (IMT) showed a
      progressive increase from normotensive (681 +/- 24 MUm) to MH (763 +/- 57 MUm)
      (standardized mean difference, SMD: 0.51 +/- 0.19, 95% CI 0.13-0.89, p < 0.01)
      and to sustained hypertensive subjects (787 +/- 58 MUm) (SMD: 0.33 +/- 0.07, 95%
      CI 0.20-0.46, p < 0.01). The statistical difference between MH and NT became
      borderline after correction for publication bias. A sensitivity analysis showed
      that the final result was not substantially affected by a single study effect.
      CONCLUSIONS: Our findings support the view that MH subjects tend to have a higher
      risk of developing early carotid atherosclerosis than their true normotensive
      counterparts. From a practical perspective, the ultrasound search of preclinical
      carotid disease may improve cardiovascular risk stratification and decision
      making strategies in these subjects.

PMID- 25608632
TI  - Effects of Flurbiprofen Axetil on Postoperative Analgesia and Cytokines in
      Peripheral Blood of Thoracotomy Patients.
AB  - The objective is to study the effects of flurbiprofen axetil (FA) with fentanyl
      together in postoperative controlled intravenous analgesia (PCIA) on pain
      intensity, cytokine levels in peripheral blood and adverse reactions of
      thoracotomy patients. Fifty thoracotomy patients were divided into a FA and a
      control group, each with 25 cases. Postoperative analgesia was administered in
      the two groups using PCIA. The pressing times of analgesia pump, the visual
      analog scale (VAS) scores during resting and coughing at 2, 6, 24, 48, 72 h after
      surgery and the incidence of adverse drug reactions were recorded. Levels of IL
      1beta, IL-6, IL-8, IL-2, and TNF-alpha in peripheral blood were determined before
      the administration of FA (T0), and at 24 h (T1), 48 h (T2), 72 h (T3) after
      surgery. The analgesia pump pressing times in the FA group was less than that of
      the control group. The VAS scores during resting and coughing at 2, 6, 24, 48, 72
      h after surgery, were statistically less than those of control group. The
      incidence rate of nausea and vomiting was insignificantly different between the
      two groups. Administration of FA together with PCIA in thoracotomy patients can
      improve postoperative analgesia. 

PMID- 25608633
TI  - Effects of Intermediate-Conductance Ca(2+)-Activated K(+) Channels on Human
      Endometrial Carcinoma Cells.
AB  - The objective of this study was to investigate the effect of intermediate
      conductance Ca(2+)-activated K(+) (KCa3.1) channels on the cell proliferation,
      cell cycle, apoptosis, migration, and invasion in endometrial cancer (EC) cells.
      Human EC cell lines HEC-1-A and Ishikawa were cultured in vitro and transfected
      with recombinant plasmid containing KCa3.1-targeting shRNA. RT-qPCR and Western
      blot were used to examine the mRNA and protein expression levels of KCa3.1
      channels in transfected cells. In addition, the specific inhibitor of KCa3.1,
      TRAM-34, was used to examine the effect of KCa3.1 blockage on migration capacity
      and invasiveness of EC cells using transwell assay. Proliferation and apoptotic
      rates of EC cells transfected with KCa3.1 shRNA or treated with TRAM-34 were
      analyzed using MTT, BrdU incorporation assay, and flow cytometry. Expression of
      cell cycle proteins and metalloproteinase-2 (MMP-2) was evaluated by RT-qPCR and
      Western blotting. TRAM-34 treatment and KCa3.1 silencing using shRNA dramatically
      suppressed both the mRNA and protein expression of KCa3.1 channels (P < 0.01)
      compared with control groups. Blockage of KCa3.1 by TRAM-34 treatment and KCa3.1
      shRNA transfection exerted inhibitory effect on cell growth of both EC cell
      lines, as demonstrated by increased cell population at G0-G1 phase and decreased
      cell population at S phase. However, both the treatments did not result in
      significant changes in the apoptotic rate (P > 0.05) compared to controls.
      Protein expressions of cyclin D1, cyclin E, and survivin were significantly
      decreased in the experimental groups comparing to control. We showed that TRAM-34
      treatment led to significantly inhibited migration, invasion, and MMP-2
      expression in HEC-1-A and Ishikawa cells, compared with the control group (P <
      0.01). Blockage of KCa3.1 channel activity or expression inhibits cell
      proliferation and cell cycle progression without inducing apoptosis in EC cells.
      Moreover, TRAM-34 could reduce the ability of EC cells to migrate and invade,
      which might be related to reduced expression of MMP-2. 

PMID- 25608634
TI  - Grey Turner's sign in acute necrotizing pancreatitis.

PMID- 25608635
TI  - Short-course radiotherapy in elderly patients with early stage non-melanoma skin
      cancer: a phase II study.
AB  - AIM: To evaluate outcome of an accelerated radiotherapy (RT) regimen in elderly
      patients with an early stage non-melanoma skin cancer (NMSC). METHODS: Total RT
      dose was 30 Gy in 5 Gy fractions in six consecutive days. RESULTS: Thirty-one
      patients were enrolled. Fourteen were aged >=80 years. Acute skin and observed
      late toxicity were exclusively of grade 1. Thirty patients showed a complete
      response (median follow-up 30 months). Two-year actuarial local control was
      93.2%. The cosmetic result was mostly judged as good or excellent. CONCLUSIONS:
      Short-course RT in elderly NMSC patients produces >90% local control of disease.

PMID- 25608636
TI  - The association between NQO1 Pro187Ser polymorphism and urinary system cancer
      susceptibility: a meta-analysis of 22 studies.
AB  - Numerous studies have investigated the association between NQO1 Pro187Ser
      polymorphism and urinary system cancer risk, but the findings are inconsistent.
      To derive a more precise estimation of such association, we performed a meta
      analysis based on 22 publications encompassing 5,274 cases and 6,459 controls.
      Overall, significant association was found between NQO1 Pro187Ser polymorphism
      and urinary system cancer risk. Moreover, stratified analysis observed a
      statistically significant association for bladder cancer, prostate cancer, renal
      cell carcinoma, Caucasians, Asians, and hospital-based studies. In summary, this
      meta-analysis indicated that NQO1 Pro187Ser polymorphism conferred genetic
      susceptibility to urinary system cancer.

PMID- 25608637
TI  - Liquid-in-liquid antibody confinement provides new possibilities for multiplexed
      diagnostics.
AB  - The accuracy of disease diagnosis and prognosis can be improved by measuring the
      concentrations of multiple biomarkers from patient samples. One of the most
      common and robust methods for detecting biomarkers from patient samples is the
      ELISA. Recently, there has been a push to improve the disease detection
      capabilities of immunoassays such as ELISA, as well as other diagnostic assays,
      by implementing multiplexing strategies. This perspective discusses recent
      progress using a unique multiplexing technology that takes advantage of phase
      separating polymers to spatially confine antibody reagents for cross-reaction
      free multiplexing of immunoassays. 

PMID- 25608639
TI  - Tracheal ultrasound to assess endotracheal tube depth: an exploratory study.

PMID- 25608638
TI  - Cardiopulmonary exercise testing, prehabilitation, and Enhanced Recovery After
      Surgery (ERAS).
AB  - PURPOSE: This review evaluates the current and future role of cardiopulmonary
      exercise testing (CPET) in the context of Enhanced Recovery After Surgery (ERAS)
      programs. PRINCIPAL FINDINGS: There is substantial literature confirming the
      relationship between physical fitness and perioperative outcome in general. The
      few small studies in patients undergoing surgery within an ERAS program describe
      less fit individuals having a greater incidence of morbidity and mortality. There
      is evidence of increasing adoption of perioperative CPET, particularly in the UK.
      Although CPET-derived variables have been used to guide clinical decisions about
      choice of surgical procedure and level of perioperative care as well as to screen
      for uncommon comorbidities, the ability of CPET-derived variables to guide
      therapy and thereby improve outcome remains uncertain. Recent studies have
      reported a reduction in CPET-defined physical fitness following neoadjuvant
      therapies (chemo- and radio-therapy) prior to surgery. Preliminary data suggest
      that this effect may be associated with an adverse effect on clinical outcomes in
      less fit patients. Early reports suggest that CPET-derived variables can be used
      to guide the prescription of exercise training interventions and thereby improve
      physical fitness in patients prior to surgery (i.e., prehabilitation). The impact
      of such interventions on clinical outcomes remains uncertain. CONCLUSIONS:
      Perioperative CPET is finding an increasing spectrum of roles, including risk
      evaluation, collaborative decision-making, personalized care, monitoring
      interventions, and guiding prescription of prehabilitation. These indications are
      potentially of importance to patients having surgery within an ERAS program, but
      there are currently few publications specific to CPET in the context of ERAS
      programs.

PMID- 25608640
TI  - Ultrasound-guided peripheral nerve blocks for total knee arthroplasty in the
      context of severe aortic stenosis: avoiding the general anesthetic.

PMID- 25608641
TI  - Neuraxial anesthesia improves long-term survival after total joint replacement: a
      retrospective nationwide population-based study in Taiwan.
AB  - INTRODUCTION: This study explored the effects of general (GA) and neuraxial (NA)
      anesthesia on the outcomes of primary total joint replacement (TJR) in terms of
      postoperative mortality, length of stay (LOS), and hospital treatment costs.
      METHODS: From 1997 to 2010, this nationwide population-based study
      retrospectively evaluated 7,977 patients in Taiwan who underwent primary total
      hip or knee replacement. We generated two propensity-score-matched subgroups,
      each containing an equal number of patients who underwent TJR with either GA or
      NA. RESULTS: Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%)
      underwent NA. Propensity-score matching was used to create comparable GA and NA
      groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and
      surgeon volume. Survival over the first three years following surgery was
      similar. The proportion of patients alive up to 14 years postoperatively for
      those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and
      for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia
      was associated with lower median [interquartile range; IQR] hospital treatment
      cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P < 0.001) and shorter median
      [IQR] LOS (8 [7-10] days vs 8 [6-10] days, respectively; P = 0.024). CONCLUSIONS:
      Our results support the use of NA for primary TJR. The improvements in hospital
      costs persist even when anesthesia costs are removed. The mechanism underlying
      the association between NA and long-term survival is unknown.

PMID- 25608642
TI  - Teaching blind nasal intubation in Rwanda.

PMID- 25608643
TI  - Jammed elastic shells - a 3D experimental soft frictionless granular system.
AB  - We present a new experimental system of monodisperse, soft, frictionless,
      fluorescent labeled elastic shells for the characterization of structure,
      universal scaling laws and force networks in 3D jammed matter. The elastic shells
      in a jammed packing are deformed in such a way that at each contact one of the
      shells buckles with a dimple and the other remain spherical, closely resembling
      overlapping spheres. Using confocal microscopy, we obtained 3D stacks of images
      of shells at different volume fractions which were subsequently processed in
      ImageJ software to find their coordinates. The determination of 3D coordinates
      involved three steps: locating the edges of shells in all 2D slices, analyzing
      their shape and subsequently finding their 2D coordinates, and finally
      determining their 3D centers by grouping the corresponding 2D coordinates. From
      this analysis routine we obtained particle coordinates with sub-pixel accuracy.
      In a contact pair we also identified the shell that underwent buckling forming a
      dimple by analyzing the intensity profile of a line that connects the centers of
      particle pairs. The amorphous structure of the packing was analyzed as a function
      of distance to the jamming threshold by investigating the radial distribution
      function, bond order parameters, contact numbers and the number of dimples per
      particle (buckling number), which is a unique property of this system. We find
      that the power law scaling of the contact number with excess volume fraction
      deviated from theoretical and computer simulation predictions. In addition, the
      buckling number also showed a similar scaling as that of the contact number with
      distance to the jamming transition. 

PMID- 25608645
TI  - Kinetic analysis for the isomerization of glucose, fructose, and mannose in
      subcritical aqueous ethanol.
AB  - Fructose, glucose, and mannose were treated with subcritical aqueous ethanol for
      ethanol concentrations ranging from 0 to 80% (v/v) at 180-200  degrees C. The
      aldose-ketose isomerization was more favorable than ketose-aldose isomerization
      and glucose-mannose epimerization. The isomerization of the monosaccharides was
      promoted by the addition of ethanol. In particular, mannose was isomerized most
      easily to fructose in subcritical aqueous ethanol. The apparent equilibrium
      constants for the isomerizations of mannose to fructose, Keq,M->F, and glucose to
      fructose, Keq,G->F, were independent of ethanol concentration and increased with
      increasing temperature. Moreover, the Keq,M->F value was much larger than the
      Keq,G->F value. The enthalpies for the isomerization of mannose to fructose,
      DeltaHM->F, and glucose to fructose, DeltaHG->F, were estimated to be 18 and 24
      kJ/mol, respectively, according to van't Hoff equation. Subcritical aqueous
      ethanol can be used to produce fructose from glucose and mannose efficiently. 

PMID- 25608644
TI  - Osmotic pressure induced tensile forces in tendon collagen.
AB  - Water is an important component of collagen in tendons, but its role for the
      function of this load-carrying protein structure is poorly understood. Here we
      use a combination of multi-scale experimentation and computation to show that
      water is an integral part of the collagen molecule, which changes conformation
      upon water removal. The consequence is a shortening of the molecule that
      translates into tensile stresses in the range of several to almost 100 MPa,
      largely surpassing those of about 0.3 MPa generated by contractile muscles.
      Although a complete drying of collagen would be relevant for technical
      applications, such as the fabrication of leather or parchment, stresses
      comparable to muscle contraction already occur at small osmotic pressures common
      in biological environments. We suggest, therefore, that water-generated tensile
      stresses may play a role in living collagen-based materials such as tendon or
      bone.

PMID- 25608647
TI  - The Mayo Clinic Department of Orthopedic Surgery: an international foundation.

PMID- 25608646
TI  - Lipid abnormalities in patients with adrenal incidentalomas: role of subclinical
      hypercortisolism and impaired glucose metabolism.
AB  - BACKGROUND: Subclinical hypercortisolism (SH) has been associated with metabolic
      complications such as type 2 diabetes mellitus, obesity and dyslipidemia. Scarce
      data are available regarding the lipid pattern abnormalities in SH, in relation
      to insulin resistance and impaired glucose metabolism (IGM). We aimed to evaluate
      the possible influence of SH on lipid pattern in relation to the presence/absence
      of impaired glucose metabolism. METHODS: In 338 patients with adrenal
      incidentaloma, the presence of SH, hypertension, dyslipidemia and IGM was
      evaluated. According to the presence of SH and IGM the patients were divided into
      4 groups (IGM+SH+, IGM+SH-, IGM-SH+, IGM-SH-). We recruited 98 subjects without
      IGM (IGM-) and 100 with IGM (IGM+) as control groups. RESULTS: The prevalence of
      dyslipidemia was comparable among Group IGM+SH+, Group IGM+SH- and IGM+ controls
      (57.9, 58.4, 56%, P = NS). No difference in dyslipidemia prevalence among IGM-
      patients and IGM- controls was observed. The IGM+SH+ patients had a higher
      prevalence of dyslipidemia (57.9%) than IGM-SH+ ones (29.1%, P < 0.01). The
      IGM+SH- patients showed an increased prevalence of hypertension (76.6 vs 54.8%, P
      < 0.01) and dyslipidemia (58.4 vs 23.8%, P < 0.0001) as compared with IGM-SH-
      patients. Logistic regression analysis showed that only IGM was associated to
      dyslipidemia (OR 4.31, 95% CI 2.61-7.12, P = 0.0001) regardless of age, SH and
      gender. CONCLUSIONS: In the absence of alterations of glucose metabolism the
      presence of a subtle cortisol excess has no effect on lipid pattern. IGM seems to
      influence the lipid metabolism regardless of the presence of SH.

PMID- 25608648
TI  - Economic burden of illness associated with diabetic foot ulcers in Canada.
AB  - BACKGROUND: The primary objective was to estimate the national burden of illness
      in Canada for diabetic foot ulcer (DFU) for 2011. Secondary objectives included
      estimating the national incidence and prevalence of DFU, and the 3-year average
      cost for DFU incident cases. METHODS: Analyses were conducted using four national
      databases for the period April 1, 2006 to March 31, 2011, with cases being
      identified by ICD-10 CA codes. Resource utilization and costs, expressed in 2011
      Canadian dollars, were estimated for DFU-related hospitalizations, emergency care
      (ER), same day surgeries, home care, long term care, physician visits and
      caregiver time losses. RESULTS: In Canada in the year 2011, DFU was associated
      with 16,883 hospital admissions (327,140 days), 31,095 ER or clinic visits,
      41,367 rehabilitation clinic visits, and 26,493 interventions, including 6,036
      amputations and 5,796 surgical debridements. This acute institution care
      represented $320.5 M, and with an additional $125.4 M for home care and $63.1 M
      for long term care, the annual cost associated with DFU-related care was $547.0
      M, or $21,371 annual cost per prevalent case. In 2011, the national prevalence of
      DFU was 25,597 cases (75.1 per 100,000 population), consisting of 16,161 men
      (63.1%) and 9,436 women (36.9%), and an estimated 14,449 incident cases. For an
      incident case of DFU, the average 3-year cumulative cost was $52,360. CONCLUSION:
      The annual burden for DFU cases that have at least one admission or ER/clinic
      visit over a 5 year period is higher than previously reported.

PMID- 25608649
TI  - Mechanisms of hyperhomocysteinemia induced skeletal muscle myopathy after
      ischemia in the CBS-/+ mouse model.
AB  - Although hyperhomocysteinemia (HHcy) elicits lower than normal body weights and
      skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that
      HHcy-mediated enhancement in ROS and consequent damage to regulators of different
      cellular processes is relatively well established in other organs, the nature of
      such events is unknown in skeletal muscles. Previously, we reported that HHcy
      attenuation of PGC-1alpha and HIF-1alpha levels enhanced the likelihood of muscle
      atrophy and declined function after ischemia. In the current study, we examined
      muscle levels of homocysteine (Hcy) metabolizing enzymes, anti-oxidant capacity
      and focused on protein modifications that might compromise PGC-1alpha function
      during ischemic angiogenesis. Although skeletal muscles express the key enzyme
      (MTHFR) that participates in re-methylation of Hcy into methionine, lack of trans
      sulfuration enzymes (CBS and CSE) make skeletal muscles more susceptible to the
      HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS-/+
      mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to
      enhanced total protein as well as PGC-1alpha specific nitrotyrosylation after
      ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy)
      or its cyclized version, Hcy thiolactone, not only increased PGC-1alpha specific
      protein nitrotyrosylation but also reduced its association with PPARgamma in
      C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic
      effects via reduction of the PGC-1/PPARgamma axis after ischemia. 

PMID- 25608650
TI  - Unravelling genes and pathways implicated in working memory of schizophrenia in
      Han Chinese.
AB  - Working memory deficit is the core neurocognitive disorder in schizophrenia
      patients. To identify the factors underlying working memory deficit in
      schizophrenia patients and to explore the implication of possible genes in the
      working memory using genome-wide association study (GWAS) of schizophrenia,
      computerized delay-matching-to-sample (DMS) and whole genome genotyping data were
      obtained from 100 first-episode, treatment-naive patients with schizophrenia and
      140 healthy controls from the Mental Health Centre of the West China Hospital,
      Sichuan University. A composite score, delay-matching-to-sample total correct
      numbers (DMS-TC), was found to be significantly different between the patients
      and control. On associating quantitative DMS-TC with interactive variables of
      groups * genotype, one SNP (rs1411832), located downstream of YWHAZP5 in
      chromosome 10, was found to be associated with the working memory deficit in
      schizophrenia patients with lowest p-value (p = 2.02 * 10(-7)). ConsensusPathDB
      identified that genes with SNPs for which p values below the threshold of 5 * 10(
      5) were significantly enriched in GO:0007155 (cell adhesion, p < 0.001). This
      study indicates that working memory, as an endophenotype of schizophrenia, could
      improve the efficacy of GWAS in schizophrenia. However, further study is required
      to replicate the results from our study.

PMID- 25608651
TI  - Molecular characterization of a new wheat-Thinopyrum intermedium translocation
      line with resistance to powdery mildew and stripe rust.
AB  - A new wheat-Thinopyrum translocation line CH13-21 was selected from the progenies
      derived from a cross between wheat-Th. intermedium partial amphiploid TAI7047 and
      wheat line Mianyang11. CH13-21 was characterized by using genomic in situ
      hybridization (GISH), multicolor-GISH (mc-GISH), multicolor-fluorescence in situ
      hybridization (mc-FISH) and chromosome-specific molecular markers. When
      inoculated with stripe rust and powdery mildew isolates, CH13-21 displayed novel
      resistance to powdery mildew and stripe rust which inherited from its Thinopyrum
      parent. The chromosomal counting analyses indicated that CH13-21 has 42
      chromosomes, with normal bivalent pairing at metaphase I of meiosis. GISH probed
      by Th. intermedium genomic DNA showed that CH13-21 contained a pair of wheat-Th.
      intermedium translocated chromosomes. Sequential mc-FISH analyses probed by
      pSc119.2 and pAs1 clearly revealed that chromosome arm 6BS of CH13-21 was
      replaced by Thinopyrum chromatin in the translocation chromosome. The molecular
      markers analysis further confirmed that the introduced Th. intermedium chromatin
      in CH13-21 belonged to the long arm of homoeologous group 6 chromosome.
      Therefore, CH13-21 was a new T6BS.6Ai#1L compensating Robertsonian translocation
      line. It concludes that CH13-21 is a new genetic resource for wheat breeding
      programs providing novel variation for disease resistances. 

PMID- 25608652
TI  - Transgenic plants as low-cost platform for chemotherapeutic drugs screening.
AB  - In this work we explored the possibility of using genetically modified
      Arabidopsis thaliana plants as a rapid and low-cost screening tool for evaluating
      human anticancer drugs action and efficacy. Here, four different inhibitors with
      a validated anticancer effect in humans and distinct mechanism of action were
      screened in the plant model for their ability to interfere with the cytoskeletal
      and endomembrane networks. We used plants expressing a green fluorescent protein
      (GFP) tagged microtubule-protein (TUA6-GFP), and three soluble GFPs differently
      sorted to reside in the endoplasmic reticulum (GFPKDEL) or to accumulate in the
      vacuole through a COPII dependent (AleuGFP) or independent (GFPChi) mechanism.
      Our results demonstrated that drugs tested alone or in combination differentially
      influenced the monitored cellular processes including cytoskeletal organization
      and endomembrane trafficking. In conclusion, we demonstrated that A. thaliana
      plants are sensitive to the action of human chemotherapeutics and can be used for
      preliminary screening of drugs efficacy. The cost-effective subcellular imaging
      in plant cell may contribute to better clarify drugs subcellular targets and
      their anticancer effects. 

PMID- 25608653
TI  - Experimental confirmation of a whole set of tRNA molecules in two archaeal
      species.
AB  - Based on the genomic sequences for most archaeal species, only one tRNA gene
      (isodecoder) is predicted for each triplet codon. This observation promotes
      analysis of a whole set of tRNA molecules and actual splicing patterns of
      interrupted tRNA in one organism. The entire genomic sequences of two
      Creanarchaeota, Aeropyrum pernix and Sulfolobus tokodaii, were determined
      approximately 15 years ago. In these genome datasets, 47 and 46 tRNA genes were
      detected, respectively. Among them, 14 and 24 genes, respectively, were predicted
      to be interrupted tRNA genes. To confirm the actual transcription of these
      predicted tRNA genes and identify the actual splicing patterns of the predicted
      interrupted tRNA molecules, RNA samples were prepared from each archaeal species
      and used to synthesize cDNA molecules with tRNA sequence-specific primers.
      Comparison of the nucleotide sequences of cDNA clones representing unspliced and
      spliced forms of interrupted tRNA molecules indicated that some introns were
      located at positions other than one base 3' from anticodon region and that bulge
      helix-bulge structures were detected around the actual splicing sites in each
      interrupted tRNA molecule. Whole-set analyses of tRNA molecules revealed that the
      archaeal tRNA splicing mechanism may be essential for efficient splicing of all
      tRNAs produced from interrupted tRNA genes in these archaea. 

PMID- 25608654
TI  - Identification and analysis of differentially-expressed microRNAs in Japanese
      encephalitis virus-infected PK-15 cells with deep sequencing.
AB  - Japanese encephalitis virus (JEV), a mosquito-borne Flavivirus, causes acute
      viral encephalitis with high morbidity and mortality in humans and animals.
      MicroRNAs (miRNAs) are small noncoding RNAs that are important modulators of the
      intricate host-pathogen interaction networks. However, our knowledge of the
      changes that occur in miRNAs in host cells after JEV infection is still limited.
      To understand the molecular pathogenesis of JEV at the level of
      posttranscriptional regulation, we used Illumina deep sequencing to sequence two
      small RNA libraries prepared from PK-15 cells before and after JEV infection. We
      identified 522 and 427 miRNAs in the infected and uninfected cells, respectively.
      Overall, 132 miRNAs were expressed significantly differently after challenge with
      JEV: 78 were upregulated and 54 downregulated. The sequencing results for
      selected miRNAs were confirmed with RT-qPCR. GO analysis of the host target genes
      revealed that these dysregulated miRNAs are involved in complex cellular
      pathways, including the metabolic pathway, inflammatory response and immune
      response. To our knowledge, this is the first report of the comparative
      expression of miRNAs in PK-15 cells after JEV infection. Our findings will
      underpin further studies of miRNAs' roles in JEV replication and identify
      potential candidates for antiviral therapies against JEV. 

PMID- 25608655
TI  - De novo assembly and characterization of narrow-ridged finless porpoise renal
      transcriptome and identification of candidate genes involved in osmoregulation.
AB  - During the evolutionary transition from land to water, cetaceans have undergone
      numerous critical challenges, with osmoregulation being the major one. Two
      subspecies of the narrow-ridged finless porpoise (Neophocaena asiaeorientalis),
      the freshwater Yangtze finless porpoise (N. a. asiaeorientalis, NAA) and the
      marine East Asian finless porpoise (N. a. sunameri, NAS), provide excellent
      subjects to understand the genetic basis of osmoregulatory divergence between
      freshwater and marine mammals. The kidney plays an important and well-established
      role in osmoregulation in marine mammals and thus, herein, we utilized RNA-seq to
      characterize the renal transcriptome and preliminarily analyze the divergence
      between the NAA and the NAS. Approximately 48.98 million clean reads from NAS and
      49.40 million clean reads from NAA were obtained by RNA-Seq. And 73,449 (NAS) and
      68,073 (NAA) unigenes were assembled. Among these annotations, 22,231 (NAS) and
      21,849 (NAA) unigenes were annotated against the NCBI nr protein database. The
      ion channel complex GO term and four pathways were detected as relevant to
      osmoregulation by GO and KEGG pathway classification of these annotated unigenes.
      Although the endangered status of the study species prevented analysis of
      biological replicates, we identified nine differentially expressed genes (DEGs)
      that may be vital in the osmoregulation of the narrow-ridged finless porpoise and
      worthwhile for future studies. Of these DEGs, the differential expression and
      distribution of the aquaporin-2 (AQP2) in the collecting duct were verified using
      immunohistochemical experiments. Together, this work is the first report of renal
      transcriptome sequencing in cetaceans, and it will provide a valuable resource
      for future molecular genetics studies on cetacean osmoregulation. 

PMID- 25608656
TI  - Mechanical and anticorrosive properties of graphene/epoxy resin composites
      coating prepared by in-situ method.
AB  - The graphene nanosheets-based epoxy resin coating (0, 0.1, 0.4 and 0.7 wt %) was
      prepared by a situ-synthesis method. The effect of polyvinylpyrrolidone/reduced
      graphene oxide (PVP-rGO) on mechanical and thermal properties of epoxy resin
      coating was investigated using nanoindentation technique and thermogravimetric
      analysis, respectively. A significant enhancement (ca. 213% and 73  degrees C) in
      the Young modulus and thermal stability of epoxy resin coating was obtained at a
      loading of 0.7 wt %, respectively. Furthermore, the erosion resistance of
      graphene nanosheets-based epoxy resin coating was investigated by electrochemical
      measurement. The results showed also that the Rrcco (ca. 0.3 mm/year) of graphene
      nanosheets-based epoxy resin coating was far lower than neat epoxy resin (1.3
      mm/year). Thus, this approach provides a novel route for improving erosion
      resistance and mechanical-thermal stability of polymers coating, which is
      expected to be used in mechanical-thermal-corrosion coupling environments. 

PMID- 25608658
TI  - Exploration of Na(2.65)Ti(3.35)Fe(0.65)O9 as anode materials for Na-ion
      batteries.
AB  - Na(2.65)Ti(3.35)Fe(0.65)O9 rods were prepared by a simple solid-state route and
      coated with carbon to enhance their electronic conductivity. For the first time,
      Na(2.65)Ti(3.35)Fe(0.65)O9 was explored as an anode material for Na-ion batteries
      to deliver a discharge capacity of 137.5 mA h g(-1) at a current rate of 40 mA g(
      1). The charge/discharge capacity of a carbon-coated sample increased by 46.3% to
      achieve 201.1 mA h g(-1).

PMID- 25608657
TI  - Inhibition of the IgE-mediated activation of RBL-2H3 cells by TIPP, a novel
      thymic immunosuppressive pentapeptide.
AB  - TIPP is a novel thymic immunosuppressive pentapeptide originally obtained from
      calf thymic immunosuppressive extract. The present study aimed to investigate the
      inhibitory activity of TIPP on IgE-mediated activation of RBL-2H3 cells. Release
      of beta-hexosaminidase and histamine, intracellular calcium, membrane ruffling,
      mRNA levels of cytokines, cyclooxygenase-2 (COX-2) expression, and activation of
      mitogen-activated protein kinases (MAP kinases) and NF-kappaB were determined by
      colorimetric assay, fluorescence spectrophotometer, confocal fluorescence
      microscope, quantification PCR, and Western blot, respectively. The results
      showed that TIPP significantly inhibited the degranulation in IgE-antigen complex
      stimulated RBL-2H3 cells without cytotoxicity. TIPP significantly suppressed the
      increase of intracellular calcium and the rearrangement of F-actin, attenuated
      the transcription of pro-inflammatory cytokines (IL-3, -4, -6, -13, TNF-alpha,
      and monocyte chemotactic protein-1 (MCP-1)), and decreased the expression of COX
      2. Western blot analysis showed that TIPP had an inhibitory activity on the
      phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and
      ERK kinase 1/2 (MEK1/2), and inhibited the activation of NF-kappaB. The data
      suggested that TIPP effectively suppressed IgE-mediated activation of RBL-2H3
      cells via blocking MEK/ERK and NF-kappaB signaling pathways. 

PMID- 25608659
TI  - Genomic organization of the crested ibis MHC provides new insight into ancestral
      avian MHC structure.
AB  - The major histocompatibility complex (MHC) plays an important role in immune
      response. Avian MHCs are not well characterized, only reporting highly compact
      Galliformes MHCs and extensively fragmented zebra finch MHC. We report the first
      genomic structure of an endangered Pelecaniformes (crested ibis) MHC containing
      54 genes in three regions spanning ~500 kb. In contrast to the loose BG (26 loci
      within 265 kb) and Class I (11 within 150) genomic structures, the Core Region is
      condensed (17 within 85). Furthermore, this Region exhibits a COL11A2 gene,
      followed by four tandem MHC class II alphabeta dyads retaining two suites of
      anciently duplicated "alphabeta" lineages. Thus, the crested ibis MHC structure
      is entirely different from the known avian MHC architectures but similar to that
      of mammalian MHCs, suggesting that the fundamental structure of ancestral avian
      class II MHCs should be "COL11A2-IIalphabeta1-IIalphabeta2." The gene structures,
      residue characteristics, and expression levels of the five class I genes reveal
      inter-locus functional divergence. However, phylogenetic analysis indicates that
      these five genes generate a well-supported intra-species clade, showing evidence
      for recent duplications. Our analyses suggest dramatic structural variation among
      avian MHC lineages, help elucidate avian MHC evolution, and provide a foundation
      for future conservation studies. 

PMID- 25608660
TI  - Impact of a countywide smoke-free workplace law on emergency department visits
      for respiratory diseases: a retrospective cohort study.
AB  - BACKGROUND: With the goal of reducing exposure to secondhand smoke, the state of
      Minnesota (MN), enacted a smoke-free law (i.e., Freedom to Breathe Act) in all
      workplaces, restaurants, and bars in 2007. This retrospective cohort study
      analyzes emergency department (ED) visits in Olmsted County, MN, for chronic
      obstructive pulmonary disease (COPD) and asthma over a five-year period to assess
      changes after enactment of the smoke-free law. METHODS: We calculated the rates
      of ED visits in Olmsted County, MN, with a primary diagnosis of COPD and asthma
      in the five-year period from January 1, 2005 to December 31, 2009. Analyses were
      performed using segmented Poisson regression to assess whether ED visit rates
      declined following enactment of the smoke free law after adjusting for potential
      underlying temporal trends in ED visit rates during this time period. RESULTS:
      Using segmented Poisson regression analyses, a significant reduction was detected
      in asthma-related ED visits (RR 0.814, p < 0.001) but not for COPD-related ED
      visits following the enactment of the smoke-free law. The reduction in asthma
      related ED visits was observed in both adults (RR 0.840, p = 0.015) and children
      (RR 0.751, p = 0.015). CONCLUSIONS: In Olmsted County, MN, asthma-related ED
      visits declined significantly after enactment of a smoke-free law. These results
      add to the body of literature supporting community health benefits of smoke-free
      policies in public environments and their potential to reduce health care costs.

PMID- 25608661
TI  - Synthesis, structural characterization and thermal properties of copper and
      silver silyl complexes.
AB  - The synthesis of copper and silver silyl complexes containing either N
      heterocyclic carbenes or nitrogen donors is described. Alterations made to both
      the neutral donor ligands as well as the silyl group provided access to a number
      of different compounds. Many of the complexes synthesized were studied in the
      solid state and the effect of the donor ligand on the final structure of the
      complexes was examined. The thermal properties of the complexes were explored
      using thermogravimetric analysis, differential scanning calorimetry and
      sublimations. Some of the complexes synthesized were demonstrated to be promising
      volatile metal precursors. 

PMID- 25608663
TI  - Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF
      mutations in intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal
      prognosis and limited therapeutic options. By performing RNA- and exome
      sequencing analyses, we report a novel fusion event, FGFR2-PPHLN1 (16%), and
      damaging mutations in the ARAF oncogene (11%). Here we demonstrate that the
      chromosomal translocation t(10;12)(q26;q12) leading to FGFR2-PPHLN1 fusion
      possesses transforming and oncogenic activity, which is successfully inhibited by
      a selective FGFR2 inhibitor in vitro. Among the ARAF mutations, N217I and G322S
      lead to activation of the pathway and N217I shows oncogenic potential in vitro.
      Screening of a cohort of 107 iCCA patients reveals that FGFR2 fusions represent
      the most recurrent targetable alteration (45%, 17/107), while they are rarely
      present in other primary liver tumours (0/100 of hepatocellular carcinoma (HCC);
      1/21 of mixed iCCA-HCC). Taken together, around 70% of iCCA patients harbour at
      least one actionable molecular alteration (FGFR2 fusions, IDH1/2, ARAF, KRAS,
      BRAF and FGF19) that is amenable for therapeutic targeting. 

PMID- 25608662
TI  - Imaging of malignancies of the biliary tract- an update.
AB  - Malignancies of the biliary tract include cholangiocarcinoma, gallbladder cancers
      and carcinoma of the ampulla of Vater. Biliary tract adenocarcinomas are the
      second most common primary hepatobiliary cancer. Due to their slow growing
      nature, non-specific and late symptomatology, these malignancies are often
      diagnosed in advanced stages with poor prognosis. Apart from incidental discovery
      of gall bladder carcinoma upon cholecystectomy, early stage biliary tract cancers
      are now detected with computed tomography (CT) and magnetic resonance imaging
      (MRI) with magnetic resonance cholangiopancreatography (MRCP). Accurate
      characterization and staging of these indolent cancers will determine outcome as
      majority of the patients' are inoperable at the time of presentation. Ultrasound
      is useful for initial evaluation of the biliary tract and gallbladder masses and
      in determining the next suitable modality for further evaluation. Multimodality
      imaging plays an integral role in the management of the biliary tract
      malignancies. The imaging techniques most useful are MRI with MRCP, endoscopic
      retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and
      positron emission tomography (PET). In this review we will discuss epidemiology
      and the role of imaging in detection, characterization and management of the
      biliary tract malignancies under the three broad categories of
      cholangiocarcinomas (intra- and extrahepatic), gallbladder cancers and ampullary
      carcinomas. 

PMID- 25608664
TI  - CO2 enrichment and N addition increase nutrient loss from decomposing leaf litter
      in subtropical model forest ecosystems.
AB  - As atmospheric CO2 concentration increases, many experiments have been carried
      out to study effects of CO2 enrichment on litter decomposition and nutrient
      release. However, the result is still uncertain. Meanwhile, the impact of CO2
      enrichment on nutrients other than N and P are far less studied. Using open-top
      chambers, we examined effects of elevated CO2 and N addition on leaf litter
      decomposition and nutrient release in subtropical model forest ecosystems. We
      found that both elevated CO2 and N addition increased nutrient (C, N, P, K, Ca,
      Mg and Zn) loss from the decomposing litter. The N, P, Ca and Zn loss was more
      than tripled in the chambers exposed to both elevated CO2 and N addition than
      those in the control chambers after 21 months of treatment. The stimulation of
      nutrient loss under elevated CO2 was associated with the increased soil moisture,
      the higher leaf litter quality and the greater soil acidity. Accelerated nutrient
      release under N addition was related to the higher leaf litter quality, the
      increased soil microbial biomass and the greater soil acidity. Our results imply
      that elevated CO2 and N addition will increase nutrient cycling in subtropical
      China under the future global change. 

PMID- 25608665
TI  - The role of vanadium in biology.
AB  - Vanadium is special in at least two respects: on the one hand, the tetrahedral
      anion vanadate(v) is similar to the phosphate anion; vanadate can thus interact
      with various physiological substrates that are otherwise functionalized by
      phosphate. On the other hand, the transition metal vanadium can easily expand its
      sphere beyond tetrahedral coordination, and switch between the oxidation states
      +v, +iv and +iii in a physiological environment. The similarity between vanadate
      and phosphate may account for the antidiabetic potential of vanadium compounds
      with carrier ligands such as maltolate and picolinate, and also for vanadium's
      mediation in cardiovascular and neuronal defects. Other potential medicinal
      applications of more complex vanadium coordination compounds, for example in the
      treatment of parasitic tropical diseases, may also be rooted in the specific
      properties of the ligand sphere. The ease of the change in the oxidation state of
      vanadium is employed by prokarya (bacteria and cyanobacteria) as well as by
      eukarya (algae and fungi) in respiratory and enzymatic functions. Macroalgae
      (seaweeds), fungi, lichens and Streptomyces bacteria have available
      haloperoxidases, and hence enzymes that enable the 2-electron oxidation of halide
      X(-) with peroxide, catalyzed by a Lewis-acidic V(V) center. The X(+) species
      thus formed can be employed to oxidatively halogenate organic substrates, a fact
      with implications also for the chemical processes in the atmosphere. Vanadium
      dependent nitrogenases in bacteria (Azotobacter) and cyanobacteria (Anabaena)
      convert N2 + H(+) to NH4(+) + H2, but are also receptive for alternative
      substrates such as CO and C2H2. Among the enigmas to be solved with respect to
      the utilization of vanadium in nature is the accumulation of V(III) by some sea
      squirts and fan worms, as well as the purport of the nonoxido V(IV) compound
      amavadin in the fly agaric. 

PMID- 25608666
TI  - Water pollutant monitoring by a whole cell array through lens-free detection on
      CCD.
AB  - Environmental contamination has become a serious problem to human and
      environmental health, as exposure to a wide range of possible contaminants
      continuously increases due to industrial and agricultural activities. Whole cell
      sensors have been proposed as a powerful tool to detect class-specific toxicants
      based upon their biological activity and bioavailability. We demonstrated a
      robust toxicant detection platform based on a bioluminescence whole cell sensor
      array biochip (LumiChip). LumiChip harbors an integrated temperature control and
      a 16-member sensor array, as well as a simple but highly efficient luminescence
      collection setup. On LumiChip, samples were infused in an oxygen-permeable
      microfluidic flow channel to reach the sensor array. Time-lapse changes in
      bioluminescence emitted by the array members were measured on a single window
      removed linear charge-coupled device (CCD) commonly used in commercial industrial
      process control or in barcode readers. Removal of the protective window on the
      linear CCD allowed lens-free direct interfacing of LumiChip to the CCD surface
      for measurement with high light collection efficiency. Bioluminescence induced by
      simulated contamination events was detected within 15 to 45 minutes. The portable
      LumiSense system utilizing the linear CCD in combination with the miniaturized
      LumiChip is a promising potential platform for on-site environmental monitoring
      of toxicant contamination. 

PMID- 25608667
TI  - Be SMART: examining the experience of implementing the NHS Health Check in UK
      primary care.
AB  - BACKGROUND: The NHS Health Check was designed by UK Department of Health to
      address increased prevalence of cardiovascular disease by identifying risk levels
      and facilitating behaviour change. It constituted biomedical testing,
      personalised advice and lifestyle support. The objective of the study was to
      explore Health Care Professionals' (HCPs) and patients' experiences of delivering
      and receiving the NHS Health Check in an inner-city region of England. METHODS:
      Patients and HCPs in primary care were interviewed using semi-structured
      schedules. Data were analysed using Thematic Analysis. RESULTS: Four themes were
      identified. Firstly, Health Check as a test of 'roadworthiness' for people. The
      roadworthiness metaphor resonated with some patients but it signified a passive
      stance toward illness. Some patients described the check as useful in the theme,
      Health check as revelatory. HCPs found visual aids demonstrating levels of
      salt/fat/sugar in everyday foods and a 'traffic light' tape measure helpful in
      communicating such 'revelations' with patients. Being SMART and following the
      protocolrevealed that few HCPs used SMART goals and few patients spoke of them.
      HCPs require training to understand their rationale compared with traditional
      advice-giving. The need for further follow-up revealed disparity in follow-ups
      and patients were not systematically monitored over time. CONCLUSIONS: HCPs'
      training needs to include the use and evidence of the effectiveness of SMART
      goals in changing health behaviours. The significance of fidelity to protocol
      needs to be communicated to HCPs and commissioners to ensure consistency.
      Monitoring and measurement of follow-up, e.g., tracking of referrals, need to be
      resourced to provide evidence of the success of the NHS Health Check in terms of
      healthier lifestyles and reduced CVD risk.

PMID- 25608669
TI  - Formation of stoichiometric CsFn compounds.
AB  - Alkali halides MX, have been viewed as typical ionic compounds, characterized by
      1:1 ratio necessary for charge balance between M(+) and X(-). It was proposed
      that group I elements like Cs can be oxidized further under high pressure. Here
      we perform a comprehensive study for the CsF-F system at pressures up to 100 GPa,
      and find extremely versatile chemistry. A series of CsFn (n >= 1) compounds are
      predicted to be stable already at ambient pressure. Under pressure, 5p electrons
      of Cs atoms become active, with growing tendency to form Cs (III) and (V) valence
      states at fluorine-rich conditions. Although Cs (II) and (IV) are not
      energetically favoured, the interplay between two mechanisms (polyfluoride anions
      and polyvalent Cs cations) allows CsF2 and CsF4 compounds to be stable under
      pressure. The estimated defluorination temperatures of CsFn (n = 2,3,5) compounds
      at atmospheric pressure (218 degrees C, 150 degrees C, -15 degrees C,
      respectively), are attractive for fluorine storage applications. 

PMID- 25608668
TI  - Did female prisoners with mental disorders receive psychiatric treatment before
      imprisonment?
AB  - BACKGROUND: Throughout the world, high prevalence rates of mental disorders have
      been found in prison populations, especially in females. It has been suggested
      that these populations do not access psychiatric treatment. The aim of this study
      was to establish rates of psychiatric in- and outpatient treatments prior to
      imprisonment in female prisoners and to explore reasons for discontinuation of
      such treatments. METHODS: 150 consecutively admitted female prisoners were
      interviewed in Berlin, Germany. Socio-demographic characteristics, mental
      disorders, and previous psychiatric in- and outpatient treatments were assessed
      by trained researchers. Open questions were used to explore reasons for ending
      previous psychiatric treatment. RESULTS: A vast majority of 99 prisoners (66%;
      95% CI: 58-73) of the total sample reported that they had previously been in
      psychiatric treatment, 80 (53%; 95 CI: 45-61) in inpatient treatment, 62 (41%; 95
      CI: 34-49) in outpatient treatment and 42 (29%; 21-39) in both in- and outpatient
      treatments. All prisoners with psychosis and 72% of the ones with any lifetime
      mental health disorder had been in previous treatment. The number of inpatient
      treatments and imprisonments were positively correlated (rho = 0.27; p < 0.01).
      Inpatient treatment was described as successfully completed by 56% (N = 41) of
      those having given reasons for ending such treatment, whilst various reasons were
      reported for prematurely ending outpatient treatments. CONCLUSION: The data do
      not support the notion of a general 'mental health treatment gap' in female
      prisoners. Although inpatient care is often successfully completed, repeated
      inpatient treatments are not linked with fewer imprisonments. Improved transition
      from inpatient to outpatient treatment and services that engage female prisoners
      to sustained outpatient treatments are needed.

PMID- 25608670
TI  - RNA-Seq analysis and transcriptome assembly for blackberry (Rubus sp. Var.
      Lochness) fruit.
AB  - BACKGROUND: There is an increasing interest in berries, especially blackberries
      in the diet, because of recent reports of their health benefits due to their high
      content of flavonoids. A broad range of genomic tools are available for other
      Rosaceae species but these tools are still lacking in the Rubus genus, thus
      limiting gene discovery and the breeding of improved varieties. RESULTS: De novo
      RNA-seq of ripe blackberries grown under field conditions was performed using
      Illumina Hiseq 2000. Almost 9 billion nucleotide bases were sequenced in total.
      Following assembly, 42,062 consensus sequences were detected. For functional
      annotation, 33,040 (NR), 32,762 (NT), 21,932 (Swiss-Prot), 20,134 (KEGG), 13,676
      (COG), 24,168 (GO) consensus sequences were annotated using different databases;
      in total 34,552 annotated sequences were identified. For protein prediction
      analysis, the number of coding DNA sequences (CDS) that mapped to the protein
      database was 32,540. Non redundant (NR), annotation showed that 25,418 genes
      (73.5%) has the highest similarity with Fragaria vesca subspecies vesca.
      Reanalysis was undertaken by aligning the reads with this reference genome for a
      deeper analysis of the transcriptome. We demonstrated that de novo assembly,
      using Trinity and later annotation with Blast using different databases, were
      complementary to alignment to the reference sequence using SOAPaligner/SOAP2. The
      Fragaria reference genome belongs to a species in the same family as blackberry
      (Rosaceae) but to a different genus. Since blackberries are tetraploids, the
      possibility of artefactual gene chimeras resulting from mis-assembly was tested
      with one of the genes sequenced by RNAseq, Chalcone Synthase (CHS). cDNAs
      encoding this protein were cloned and sequenced. Primers designed to the
      assembled sequences accurately distinguished different contigs, at least for
      chalcone synthase genes. CONCLUSIONS: We prepared and analysed transcriptome data
      from ripe blackberries, for which prior genomic information was limited. This new
      sequence information will improve the knowledge of this important and healthy
      fruit, providing an invaluable new tool for biological research.

PMID- 25608671
TI  - Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis.
AB  - Several studies have yielded conflicting results on the role of antibiotic
      prophylaxis in improving outcomes in acute necrotizing pancreatitis. A meta
      analysis was carried out to investigate the impact of antibiotic prophylaxis in
      the incidence of infected pancreatic necrosis and mortality. METHODOLOGY:
      Randomized controlled trials and cohort studies investigating impact of
      prophylactic systemic antibiotic used in acute necrotizing pancreatitis were
      retrieved from online databases. An overall analysis was done with all studies
      (Group 1), followed by subgroup analyses with randomized controlled trials (Group
      2) and cohort studies (Group 3). Risk ratios (RR) were calculated for the impact
      of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and
      mortality in each group using random effects model. RESULTS: Eleven studies
      involving 864 patients were included. No significant differences in the incidence
      of infected pancreatic necrosis were observed with prophylactic antibiotic use in
      all groups. Prophylactic antibiotic use was not associated with significant
      differences in all-cause mortality in Group 2 (RR = 0.75; p = 0.24) but was
      associated with a reduction in Groups 1 (RR = 0.66, p = 0.02) and 3 (RR = 0.55, p
      = 0.04). There was no statistical difference in the incidence of fungal
      infections and surgical interventions. CONCLUSION: Antibiotic prophylaxis does
      not significantly reduce the incidence of infected pancreatic necrosis but may
      affect all-cause mortality in acute necrotizing pancreatitis.

PMID- 25608673
TI  - [Interleukin-22 - friend or foe?].

PMID- 25608672
TI  - Measles vaccine coverage estimates in an outbreak three years after the nation
      wide campaign in China: implications for measles elimination, 2013.
AB  - BACKGROUND: China is approaching measles elimination, but indigenous measles
      still circulates. County L in China has reported measles-containing vaccine (MCV)
      coverage rates >95% since 2000. Despite high reported coverage, a large measles
      outbreak occurred among young children in L County. We measured MCV coverage
      using 5 different methods during an investigation on this outbreak and compared
      our estimates with reported rates. METHODS: Reported coverage rates are
      determined by aggregating clinic-based data across the county: doses administered
      in each clinic divided by the number of children registered in each clinic. Our
      methods estimated coverage for the 2010-2012 birth cohort, and were (1)
      administrative method: doses administered in clinics divided by the birth cohort
      recorded in the Statistical Year Book, (2) house-to-house convenience-sample
      survey of children living near cases, (3) vaccination clinic records review, (4)
      determination of a convenience sample of measles outbreak cases' vaccination
      statuses and using the field vaccine efficacy outbreak equation to estimate
      population coverage, and (5) a seroprevalence survey using a convenience sample
      of residual blood samples from hospitals. RESULTS: The measles outbreak totaled
      215 cases, representing an incidence of 195.8 per million population. Our
      estimated MCV coverage rates were: (1) administrative method: 84.1%-87.0% for
      MCV1 and 80.3%-90.0% for MCV2, (2) in-house survey: 83.3% of 9-17 month children
      received MCV1, and 74.5% of 24-47 month children received MCV2, (3) clinic record
      review: 85.5% of 9-17 month children received MCV1, and 73.2% of 24-59 month
      children received MCV2, (4) field VE method: 83.6% of 9-47 month children
      received one or more MCV doses, and (5) serology: seropositive rates were <80% in
      the 12-17 and 18-23 month age cohorts. CONCLUSIONS: Compared with reported
      coverage >95%, our 5 coverage assessments all showed substantially lower
      coverage. China should evaluate guidelines for reporting vaccination coverage and
      identify feasible improvements to the assessment methods.

PMID- 25608674
TI  - [Effector T cells].
AB  - BACKGROUND: Although the present understanding of the immunopathogenesis of
      rheumatoid inflammation is still incomplete, there is substantial evidence that
      effector CD4+ T helper (Th) cells play a central role. RESULTS: In recent years,
      in addition to the established Th cell subsets Th1 and Th2 cells, other subsets,
      such as Th9, Th17, Th22 and T follicular helper (Tfh) cells have been described.
      Defining the contribution of T cells in the initiation and maintenance of
      inflammation has been augmented by the identification of functionally distinct
      subsets of effector Th cells that can be classified based on their cytokine and
      transcription factor profiles. CONCLUSION: Increasing knowledge of the role of
      these various T cell populations in chronic inflammation provides a better
      understanding and insights into the pathogenic mechanisms and chronification of
      rheumatic diseases.

PMID- 25608675
TI  - [Enthesitis in the context of spondyloarthritides].
AB  - Enthesitis is a frequent manifestation in spondyloarthritis (SpA) and psoriatic
      arthritis (PsA) and can be found in up to 40 % of patients with SpA. Because of
      the pathognomonic relevance the classification criteria for SpA and PsA use
      enthesitis as an entrance or secondary criterion. Enthesitis is most frequently
      localized at the heel but it can occur at any insertion of an enthesis into the
      bone. When diagnosing enthesitis differential diagnoses should be considered,
      mechanical-degenerative causes and fibromyalgia in particular should be excluded.
      The imaging techniques power Doppler ultrasound (PDUS) and magnetic resonance
      imaging (MRI) are most helpful in making the diagnosis. The therapeutic options
      for enthesitis are limited. Nonsteroidal antirheumatic drugs (NSARD) and local
      injections of corticosteroids are recommended. In small clinical trials no
      efficacy of disease modifying antirheumatic drugs (DMARD) could be demonstrated.
      In contrast, tumor necrosis factor alpha (TNF-alpha) blockers were shown to be
      highly effective in randomized controlled trials for SpA and PsA but they are not
      currently approved for enthesitis only. 

PMID- 25608677
TI  - Nursing identity and patient-centredness in scholarly health services research: a
      computational text analysis of PubMed abstracts 1986-2013.
AB  - BACKGROUND: The most important and contested element of nursing identity may be
      the patient-centredness of nursing, though this concept is not well-treated in
      the nursing identity literature. More conceptually-based mapping of nursing
      identity constructs are needed to help nurses shape their identity. The field of
      computational text analytics offers new opportunities to scrutinise how growing
      disciplines such as health services research construct nursing identity. This
      paper maps the conceptual content of scholarly health services research in PubMed
      as it relates to the patient-centeredness of nursing. METHODS: Computational text
      analytics software was used to analyse all health services abstracts in the
      database PubMed since 1986. Abstracts were treated as indicative of the content
      of health services research. The database PubMed was searched for all research
      papers using the term "service" or "services" in the abstract or keywords for the
      period 01/01/1986 to 30/06/2013. A total of 234,926 abstracts were obtained.
      Leximancer software was used in 1) mapping of 4,144,458 instances of 107
      concepts; 2) analysis of 106 paired concept co-occurrences for the nursing
      concept; and 3) sentiment analysis of the nursing concept versus patient, family
      and community concepts, and clinical concepts. RESULTS: Nursing is constructed
      within quality assurance or service implementation or workforce development
      concepts. It is relatively disconnected from patient, family or community care
      concepts. CONCLUSIONS: For those who agree that patient-centredness should be a
      part of nursing identity in practice, this study suggests that there is a need
      for development of health services research into both the nature of the caring
      construct in nursing identity and its expression in practice. More fundamentally,
      the study raises questions about whether health services research cultures even
      value the politically popular idea of nurses as patient-centred caregivers and
      whether they should.

PMID- 25608678
TI  - Evaluation of de novo transcriptome assemblies from RNA-Seq data.
AB  - De novo RNA-Seq assembly facilitates the study of transcriptomes for species
      without sequenced genomes, but it is challenging to select the most accurate
      assembly in this context. To address this challenge, we developed a model-based
      score, RSEM-EVAL, for evaluating assemblies when the ground truth is unknown. We
      show that RSEM-EVAL correctly reflects assembly accuracy, as measured by REF
      EVAL, a refined set of ground-truth-based scores that we also developed. Guided
      by RSEM-EVAL, we assembled the transcriptome of the regenerating axolotl limb;
      this assembly compares favorably to a previous assembly. A software package
      implementing our methods, DETONATE, is freely available at
      http://deweylab.biostat.wisc.edu/detonate. 

PMID- 25608679
TI  - A prospective investigation into the clinical impact of 4D-PET/CT in the
      characterisation of solitary pulmonary nodules.
AB  - BACKGROUND: While the effects of respiratory motion on measuring metabolic signal
      in PET/CT scanning are well known, it is still standard practice in most centres
      to scan patients while breathing freely with no correction for the effects of
      respiratory motion. The aim of this study was to investigate the impact of 4D
      PET/CT in classifying lesions in patients with a radiologically-indeterminate
      solitary pulmonary nodule. METHODS: Twenty consecutive patients with a solitary
      pulmonary nodule for investigation were prospectively recruited and completed a
      whole-body (WB)-PET/CT and 4D-PET/CT in the same session. The reporting physician
      initially classified the nodule using a 5-point scale (Definitely Malignant,
      Probably Malignant, Indeterminate, Probably benign, Definitely Benign) on the WB
      PET/CT. The physician was then shown the 4D-PET/CT and asked if they would re
      classify the lesion. Frequency, sensitivity, specificity and accuracy values were
      calculated for WB-PET/CT alone and then with the addition of the 4D-PET/CT.
      RESULTS: There were no changes in the classification for nodules initially
      classed as either benign or malignant with the addition of a 4D-PET/CT. However
      changes were observed between WB and 4D-PET/CT scans in lesions initially
      classified as indeterminate. When indeterminate lesions were defined as malignant
      there was a minor increase in sensitivity (from 73% to 75%), in specificity (56%
      63%) and in accuracy (65%-70%) but these results do not reach statistical
      significance. When the Indeterminate lesions were defined as benign there was an
      increase in sensitivity (from 55% to 67%) but there was a reduction in the
      specificity (100%-75%) and accuracy (75%-70%) with the addition of the 4D-PET/CT
      but again the results did not reach statistical significance. CONCLUSION: The
      addition of 4D-PET/CT is most likely to have an impact on those nodules initially
      classified as indeterminate on standard WB-PET/CT. In lesions classified as
      benign or malignant on standard WB-PET/CT the addition of a 4D-PET/CT is less
      likely to impact lesion classification. While 4D-PET/CT does improve the
      measurement of the metabolic signal, it does not overcome inherent limitations of
      FDG in differentiating a malignant lesion from inflammatory processes, correct
      for partial volume effects or compensate for the low intrinsic FDG-avidity of
      some malignancies.

PMID- 25608680
TI  - Analysis of vestibular-balance symptoms according to symptom duration:
      dimensionality of the Vertigo Symptom Scale-short form.
AB  - BACKGROUND: Dizziness or vertigo is associated with both vestibular-balance and
      psychological factors. A common assessment tool is the Vertigo Symptom Scale
      (VSS) -short form, which has two subscales: vestibular-balance and autonomic
      anxiety. Despite frequent use, the factor structure of the VSS-short form has yet
      to be confirmed. Here, we clarified the factor structure of the VSS-short form,
      and assessed the validity and reliability of the Japanese version of this tool.
      METHODS: We conducted a cross-sectional, multicenter, psychometric evaluation of
      patients with non-central dizziness or vertigo persisting for longer than 1
      month. Participants completed the VSS-short form, the Dizziness Handicap
      Inventory, and the Hospital Anxiety and Depression Scale. They also completed the
      VSS-short form a second time 1-3 days later. The questionnaire was translated
      into Japanese and cross-culturally adapted. We conducted a confirmatory factor
      analysis followed by an exploratory factor analysis. Convergent and discriminant
      validity, internal consistency, and test-retest reliability were evaluated.
      RESULTS: The total sample and retest sample consisted of 159 and 79 participants,
      respectively. Model-fitting for a two-subscale structure in a confirmatory factor
      analysis was poor. An exploratory factor analysis produced a three-factor
      structure: long-duration vestibular-balance symptoms, short-duration vestibular
      balance symptoms, and autonomic-anxiety symptoms. Regarding convergent and
      discriminant validity, all hypotheses were clearly supported. We obtained high
      Cronbach's alpha coefficients for the total score and subscales, ranging from
      0.758 to 0.866. Total score and subscale interclass correlation coefficients for
      test-retest reliability were acceptable, ranging from 0.867 to 0.897.
      CONCLUSIONS: The VSS-short form has a three-factor structure that was cross
      culturally well-matched with previous data from the VSS-long version. Thus, it
      was suggested that vestibular-balance symptoms can be analyzed separately
      according to symptom duration, which may reflect pathophysiological factors. The
      VSS-short form can be used to evaluate vestibular-balance symptoms and autonomic
      anxiety symptoms, as well as the duration of vestibular-balance symptoms. Further
      research using the VSS-short form should be required in other languages and
      populations.

PMID- 25608681
TI  - The impact of newer nucleos(t)ide analogues on patients with hepatitis B
      decompensated cirrhosis.
AB  - BACKGROUND/AIM: Patients with HBV-related decompensated cirrhosis (HBV-DeCi)
      should be treated with potent nucleos(t)ide analogues (NA)[entecavir (ETV) or
      tenofovir (TDF)]. The aim was the evaluation of safety and efficacy in terms of
      changes in liver disease course in HBV-DeCi patients treated with ETV or TDF.
      METHODS: In 52 HBV-DeCi patients clinical and laboratory data, including
      glomerular filtration rates (GFR), were recorded. The changes in MELD (DMELD) and
      Child-Pugh (DCTP) scores between baseline and after 6 months of treatment were
      evaluated. The independent factors associated with survival were evaluated.
      RESULTS: 31 patients under TDF and 21 under ETV were evaluated. During a median
      follow-up of 22.5 months (range: 6-68), there were no differences between the two
      groups in GFR and serum phosphate levels. At the end of follow up, in the TDF
      group, 2 patients died and 3 received liver transplantations (LT), while in the
      ETV group, 1 patient died and 3 received LT. In multivariable Cox regression
      analysis, DMELD was independently associated with the outcome in the total cohort
      (HR: 1.78, 95%C.I.:1.12-2.79, P=0.013) as well as in the subgroup of naive (n=37)
      patients (HR: 1.8, 95%C.I.:1.19-4.5, P=0.03). Finally, in the non-hepatocellular
      carcinoma patients, the DCTP score was independently associated with the outcome
      in the total cohort (HR: 2.64, 95%C.I.: 1.21-7.29, P=0.015). CONCLUSIONS: TDF and
      ETV appear to have similar renal safety profile in HBV-DeCi patients. DMELD score
      in the total cohort and DCTP score in non-HCC patients were independently
      associated with the outcome; these findings need confirmation in larger studies.

PMID- 25608682
TI  - Clinical characteristics of congenital and developmental cataract undergoing
      surgical treatment.
AB  - PURPOSE: To analyze the clinical characteristics of congenital/developmental
      cataract undergoing surgery. METHODS: A mail questionnaire was sent to 49
      facilities engaged in surgical treatment of congenital cataracts, and data on
      preoperative clinical features were collected. RESULTS: Twenty nine facilities
      reported on 864 eyes of 521 patients with congenital/infantile cataract, ranging
      in age at initial visit from 0 to 18.8 years (2.6 +/- 3.3 years, mean +/-
      standard deviation). Among the patients, 65.8 % had bilateral cataracts and 34.2
      % were unilaterally affected. Family history was found for 22.4 % of cases, of
      which 98.1 % were bilateral. Family history was positive for 33.1 % of bilateral
      and 1.3 % of unilateral cases. The most common main complaint was white pupil for
      35.7 % of bilateral cases and 32.7 % for unilateral cases. Concomitant systemic
      abnormalities were more frequently associated with bilateral cases (31.6 %) than
      with unilateral cases (16.7 %). Associated ocular diseases, such as strabismus,
      persistent fetal vasculature, and posterior lenticonus, were more frequently seen
      among unilateral cases whereas nystagmus was more common among bilateral cases.
      CONCLUSIONS: Among congenital/developmental cataracts, the ratio of bilateral and
      unilateral cases was approximately 2:1. Almost all patients with a family history
      of congenital cataract were bilateral. Initial visits to a physician were rather
      late, 2.6 years from birth; this should be improved.

PMID- 25608683
TI  - Progress in interventional cardiology: challenges for the future.
AB  - Cardiovascular disease is the leading cause of death in the western and
      developing countries. Percutaneous transluminal coronary interventions have
      become the most prevalent treatment option for coronary artery disease; however,
      due to serious complications, such as stent thrombosis and in-stent restenosis
      (ISR), the efficacy and safety of the procedure remain important issues to
      address. Strategies to overcome these aspects are under extensive investigation.
      In this review, we summarise relevant milestones during the time to overcome
      these limitations of coronary stents, such as the development of polymer-free
      drug-eluting stents (DES) to avoid pro-inflammatory response due to the polymer
      coating or the developement of stents with cell-directing drugs to,
      simultaneously, improve re-endothelialisation and inhibit ISR amongst other
      techniques most recently developed, which have not fully entered the clinical
      stage. Also the novel concept of fully biodegradable DES featured by the lack of
      a permanent foreign body promises to be a beneficial and applicable tool to
      restore a natural vessel with maintained vasomotion and to enable optional
      subsequent surgical revascularisation.

PMID- 25608684
TI  - Addressing implementation challenges during guideline development - a case study
      of Swedish national guidelines for methods of preventing disease.
AB  - BACKGROUND: Many of the world's life threatening diseases (e.g. cancer, heart
      disease, stroke) could be prevented by eliminating life-style habits such as
      tobacco use, unhealthy diet, physical inactivity and excessive alcohol use.
      Incorporating evidence-based research on methods to change unhealthy lifestyle
      habits in clinical practice would be equally valuable. However gaps between
      guideline development and implementation are well documented, with implications
      for health care quality, safety and effectiveness. The development phase of
      guidelines has been shown to be important both for the quality in guideline
      content and for the success of implementation. There are, however, indications
      that guidelines related to general disease prevention methods encounter specific
      barriers compared to guidelines that are diagnosis-specific. In 2011 the Swedish
      National board for Health and Welfare launched guidelines with a preventive
      scope. The aim of this study was to investigate how implementation challenges
      were addressed during the development process of these disease preventive
      guidelines. METHODS: Seven semi-structured interviews were conducted with members
      of the guideline development management group. Archival data detailing the
      guideline development process were also collected and used in the analysis.
      Qualitative data were analysed using content analysis as the analytical
      framework. RESULTS: The study identified several strategies and approaches that
      were used to address implementation challenges during guideline development. Four
      themes emerged from the analysis: broad agreements and consensus about scope and
      purpose; a formalized and structured development procedure; systematic and active
      involvement of stakeholders; and openness and transparency in the specific
      guideline development procedure. Additional factors concerning the scope of
      prevention and the work environment of guideline developers were perceived to
      influence the possibilities to address implementation issues. CONCLUSIONS: This
      case study provides examples of how guideline developers perceive and approach
      the issue of implementation during the development and early launch of prevention
      guidelines. Models for guideline development could benefit from an initial
      assessment of how the guideline topic, its target context and stakeholders will
      affect the upcoming implementation.

PMID- 25608687
TI  - Finnish physicians' attitudes towards active euthanasia have become more positive
      over the last 10 years.
AB  - INTRODUCTION: Most physicians are against active euthanasia. Very little is known
      about the possible changes in the attitudes of physicians. METHODS: A
      questionnaire was sent to a random sample of 1003 Finnish physicians of working
      age. A similar questionnaire had been sent to a random sample of Finnish
      physicians also in 1993 and 2003. The questionnaire consisted of statements about
      euthanasia, for which the participants were asked to express their agreement or
      disagreement on a 5-point Likert scale. RESULTS: In general, Finnish physicians'
      attitudes towards active euthanasia have become considerably more positive. In
      2003, 61% of the respondents were against the legalisation of euthanasia and 29%
      supported it. In 2013, both groups were of equal size (46%). The willingness to
      perform active euthanasia has not, however, increased significantly, even in a
      legalised setting. CONCLUSIONS: The attitudes of Finnish physicians towards
      active euthanasia became considerably more positive between 2003 and 2013. There
      was no significant change, however, in the willingness to practice euthanasia if
      it became legal.

PMID- 25608686
TI  - The anti-angiogenic and cytotoxic effects of the boswellic acid analog BA145 are
      potentiated by autophagy inhibitors.
AB  - BACKGROUND: While angiogenesis inhibitors represent a viable cancer therapy,
      there is preclinical and clinical data to suggest that many tumors develop
      resistance to such treatments. Moreover, previous studies have revealed a complex
      association between autophagy and angiogenesis, and their collective influence on
      tumorigenesis. Autophagy has been implicated in cytoprotection and tumor
      promotion, and as such may represent an alternative way of targeting apoptosis
      resistant cancer cells. This study explored the anti-cancer agent and boswellic
      acid analog BA145 as an inducer of autophagy and angiogenesis-mediated
      cytoprotection of tumor cells. METHODS: Flow cytometry, western blotting, and
      confocal microscopy were used to investigate the role of BA145 mediated
      autophagy. ELISA, microvessel sprouting, capillary structure formation, aortic
      ring and wound healing assays were performed to determine the relationship
      between BA145 triggered autophagy and angiogenesis. Flow cytometery, western
      blotting, and microscopy were employed to examine the mechanism of BA145 induced
      cell death and apoptosis. Live imaging and tumor volume analysis were carried out
      to evaluate the effect of BA145 triggered autophagy on mouse tumor xenografts.
      RESULTS: BA145 induced autophagy in PC-3 cancer cells and HUVECs significantly
      impeded its negative regulation on cell proliferation, migration, invasion and
      tube formation. These effects of BA145 induced autophagy were observed under both
      normoxic and hypoxic conditions. However, inhibition of autophagy using either
      pharmacological inhibitors or RNA interference enhanced the BA145 mediated death
      of these cells. Similar observations were noticed with sunitinib, the anti
      angiogenic properties of which were significantly enhanced during combination
      treatments with autophagy inhibitors. In mouse tumor xenografts, co-treatment
      with chloroquinone and BA145 led to a considerable reduction in tumor burden and
      angiogenesis compared to BA145 alone. CONCLUSION: These studies reveal the
      essential role of BA145 triggered autophagy in the regulation of angiogenesis and
      cytoprotection. It also suggests that the combination of the autophagy inhibitors
      with chemotherapy or anti-angiogenic agents may be an effective therapeutic
      approach against cancer.

PMID- 25608688
TI  - Treatment of whistleblowers is "stain on reputation of NHS," say MPs.

PMID- 25608690
TI  - Does ethnicity have an impact on duration of untreated psychoses: A retrospective
      study in Singapore.
AB  - BACKGROUND: Some studies have suggested ethnicity as being one of the causes
      leading to a longer duration of untreated psychosis (DUP) in first episode
      psychosis. AIM: We sought to investigate this issue, in a large cohort of
      patients with a first episode of psychosis, in Singapore. METHOD: In this
      naturalistic retrospective study, 794 patients accepted into Early Psychosis
      Intervention Programme (EPIP) services in Singapore were recruited. Diagnosis was
      made based on SCID 1 (Structured Clinical Interview for Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), Axis I Disorders).
      Information about DUP and sociodemographic characteristics was collected from
      patients and relatives. Positive and Negative Symptom Scale (PANSS) and Global
      Assessment of Functioning (GAF) Scale were used as tools to assess the severity
      of symptoms and functioning of the patient, respectively, at baseline, 3, 6, 12
      and 24  months. RESULTS: The mean and 50th quantile (median) of DUP for this
      sample were 14.2 and 6, respectively. The mean and median DUP were higher among
      Indians than in the other ethnic groups. After adjusting for demographic
      variables, Indian ethnicity was significantly associated with higher median and
      75th Percentile DUP than Chinese. Secondary and tertiary education and diagnosis
      of affective psychosis and brief psychotic disorder (vs. schizophrenia spectrum
      and delusional disorder) were also significantly associated with lower mean,
      median and 75th percentile DUP symptoms. Increase in age was significantly
      associated with higher mean, median and 75th percentile DUP while married and
      separated/divorced (vs. single) was significantly associated with lower mean and
      75th percentile DUP. CONCLUSION: This study found a positive correlation between
      certain ethnic groups and DUP. Indian ethnicity, older age, single, lower
      education and patients diagnosed with schizophrenia spectrum and delusional
      disorders were more likely to be associated with longer DUP.

PMID- 25608691
TI  - Illness in breastfeeding infants relates to concentration of lactoferrin and
      secretory Immunoglobulin A in mother's milk.
AB  - BACKGROUND AND OBJECTIVES: This study aims to better understand the relationship
      between immune compounds in human milk and infant health. We hypothesized that
      the concentration of immune compounds in milk would relate to infant illness
      symptoms according to two possible theoretical paradigms. In the 'protective'
      paradigm, high concentrations of immune compounds prevent infant illness. The
      converse, the 'responsive' framework, posits that concentrations of immune
      compounds are elevated in response to infection. METHODOLOGY: Milk samples (n =
      110) and illness data were collected among the Toba of Argentina from 30 mother
      infant dyads. Samples were assayed for two immune proteins, lactoferrin and
      secretory immunoglobulin A (sIgA). Generalized estimating equations were used to
      assess the relationship between immune composition of milk and symptoms of
      illness in infants. RESULTS: Lactoferrin was positively associated with symptoms
      of illness in infants (odds ratios >1), both in the month preceding the sample
      collection and the subsequent month. sIgA was negatively associated with symptoms
      (odds ratios <1) in the preceding and subsequent months, an association which was
      particularly strong for gastrointestinal symptoms. CONCLUSIONS AND IMPLICATIONS:
      The two compounds investigated in our study had opposite relationships with
      symptoms of illness; the positive relationship between lactoferrin and illness
      lends support to our 'responsive' paradigm, and the negative relationship between
      sIgA and symptoms of illness was consistent with our 'protective' framework. That
      elevated lactoferrin is restricted to periods of illness suggests that there may
      be a cost to mother or infant associated with persistently elevated lactoferrin
      that is not incurred with elevated sIgA.

PMID- 25608689
TI  - ThermoTRPs and Pain.
AB  - The ability of the body to perceive noxious stimuli lies in a heterogeneous group
      of primary somatosensory neurons termed nociceptors. The molecular receptors of
      noxious mechanical, temperature, or chemical stimuli are expressed in these
      neurons and have drawn considerable attention as possible targets for analgesic
      development to improve treatment for the millions who suffer from chronic pain
      conditions. A number of thermoTRPs, a subset of the transient receptor potential
      family of ion channels, are activated by a wide range on noxious stimuli. In this
      review, we review the function of these channels and examine the evidence that
      thermoTRPs play a vital role in acute, inflammatory and neuropathic nociception. 

PMID- 25608692
TI  - A Fully Automated Diabetes Prevention Program, Alive-PD: Program Design and
      Randomized Controlled Trial Protocol.
AB  - BACKGROUND: In the United States, 86 million adults have pre-diabetes. Evidence
      based interventions that are both cost effective and widely scalable are needed
      to prevent diabetes. OBJECTIVE: Our goal was to develop a fully automated
      diabetes prevention program and determine its effectiveness in a randomized
      controlled trial. METHODS: Subjects with verified pre-diabetes were recruited to
      participate in a trial of the effectiveness of Alive-PD, a newly developed, 1
      year, fully automated behavior change program delivered by email and Web. The
      program involves weekly tailored goal-setting, team-based and individual
      challenges, gamification, and other opportunities for interaction. An
      accompanying mobile phone app supports goal-setting and activity planning. For
      the trial, participants were randomized by computer algorithm to start the
      program immediately or after a 6-month delay. The primary outcome measures are
      change in HbA1c and fasting glucose from baseline to 6 months. The secondary
      outcome measures are change in HbA1c, glucose, lipids, body mass index (BMI),
      weight, waist circumference, and blood pressure at 3, 6, 9, and 12 months.
      Randomization and delivery of the intervention are independent of clinic staff,
      who are blinded to treatment assignment. Outcomes will be evaluated for the
      intention-to-treat and per-protocol populations. RESULTS: A total of 340 subjects
      with pre-diabetes were randomized to the intervention (n=164) or delayed-entry
      control group (n=176). Baseline characteristics were as follows: mean age 55 (SD
      8.9); mean BMI 31.1 (SD 4.3); male 68.5%; mean fasting glucose 109.9 (SD 8.4)
      mg/dL; and mean HbA1c 5.6 (SD 0.3)%. Data collection and analysis are in
      progress. We hypothesize that participants in the intervention group will achieve
      statistically significant reductions in fasting glucose and HbA1c as compared to
      the control group at 6 months post baseline. CONCLUSIONS: The randomized trial
      will provide rigorous evidence regarding the efficacy of this Web- and Internet
      based program in reducing or preventing progression of glycemic markers and
      indirectly in preventing progression to diabetes. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01479062; http://clinicaltrials.gov/show/NCT01479062
      (Archived by WebCite at http://www.webcitation.org/6U8ODy1vo).

PMID- 25608694
TI  - Recommendations for physical activity in older adults.

PMID- 25608693
TI  - The value of glucocorticoid co-therapy in different rheumatic diseases--positive
      and adverse effects.
AB  - Glucocorticoids play a pivotal role in the management of many inflammatory
      rheumatic diseases. The therapeutic effects range from pain relief in
      arthritides, to disease-modifying effects in early rheumatoid arthritis, and to
      strong immunosuppressive actions in vasculitides and systemic lupus
      erythematosus. There are multiple indications that adverse effects are more
      frequent with the longer use of glucocorticoids and use of higher dosages, but
      high-quality data on the occurrence of adverse effects are scarce especially for
      dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease
      activity, risk factors and individual responsiveness of the patient should guide
      treatment decisions. Monitoring for adverse effects should also be tailored to
      the patient. Continuously balancing the benefits and risks of glucocorticoid
      therapy is recommended. There is an ongoing quest for new drugs with
      glucocorticoid actions without the potential to cause harmful effects, such as
      selective glucocorticoid receptor agonists, but the application of a new compound
      in clinical practice will probably not occur within the next few years. In the
      meantime, basic research on glucocorticoid effects and detailed reports on
      therapeutic efficacy and occurrence of adverse effects will be valuable in
      weighing benefits and risks in clinical practice. 

PMID- 25608695
TI  - Abnormal development of thalamic microstructure in premature neonates with
      congenital heart disease.
AB  - Preterm birth is associated with alteration in corticothalamic development, which
      underlies poor neurodevelopmental outcomes. Our hypothesis was that preterm
      neonates with CHD would demonstrate abnormal thalamic microstructure when
      compared to critically ill neonates without CHD. A secondary aim was to identify
      any association between thalamic microstructural abnormalities and perioperative
      clinical variables. We compared thalamic DTI measurements in 21 preterm neonates
      with CHD to two cohorts of neonates without CHD: 28 term and 27 preterm neonates,
      identified from the same neonatal intensive care unit. Comparison was made with
      three other selected white matter regions using ROI manual-based measurements.
      Correlation was made with post-conceptional age and perioperative clinical
      variables. In preterm neonates with CHD, there were age-related differences in
      thalamic diffusivity (axial and radial) compared to the preterm and term non-CHD
      group, in contrast to no differences in anisotropy. Contrary to our hypothesis,
      abnormal thalamic and optic radiation microstructure was most strongly associated
      with an elevated first arterial blood gas pO2 and elevated preoperative arterial
      blood gas pH (p < 0.05). Age-related thalamic microstructural abnormalities were
      observed in preterm neonates with CHD. Perinatal hyperoxemia and increased
      perioperative serum pH were associated with abnormal thalamic microstructure in
      preterm neonates with CHD. This study emphasizes the vulnerability of
      thalamocortical development in the preterm neonate with CHD.

PMID- 25608696
TI  - Pathophysiology of infantile pulmonary arterial hypertension induced by
      monocrotaline.
AB  - Pediatric pulmonary arterial hypertension (PAH) presents certain specific
      features. In this specific age group, experimental models to study the
      pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric,
      and histological progression as well as the expression of neurohumoral factors
      and regulators of cardiac transcription in an infantile model of PAH induced by
      monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT
      (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were
      instrumented for biventricular hemodynamic recording 7, 14, and 21 days after
      MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT.
      Different time point postinjections were defined for further analysis. Hearts and
      lungs were collected for morphometric characterization, assessment of right- and
      left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type
      III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness.
      mRNA quantification was undertaken for brain natriuretic peptide (BNP),
      endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1).
      Animals treated with MCT at the 8th day of life presented RV hypertrophy since
      day 14 after MCT injection. There were no differences on the RV collagen volume
      fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling
      and PAH were present on day 21, which were accompanied by an increased expression
      of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be
      useful for the study of its pathophysiology and to test new therapeutic targets
      in pediatric age group.

PMID- 25608697
TI  - Experience with levosimendan in 32 paediatric patients.
AB  - The aim of this study was to describe the off-label conditions of use for
      levosimendan in the paediatric population of a tertiary referral hospital. This
      is a retrospective observational study conducted between January 2007 and January
      2014. Inclusion criteria were as follows: 100 % of paediatric patients who
      received intravenous perfusions of levosimendan during the study period. The
      following data were gathered: age, sex, diagnosis, dose administered, duration
      and date of the perfusion, number of perfusions per patient, previous inotropic
      and concomitant treatment, side effects and survival. A total of 32 patients were
      included in the study (56 % male). The mean age at the moment of administration
      was 4 months (range 2 days-15 years). During the study period, a total of 70
      infusions were recorded. Fifteen of the 32 patients (46.9 %) received repeat
      doses, with a mean interval between doses of 8 days (range 3-37 days). The doses
      used were between 0.05 and 0.2 mcg/kg/min. Loading doses were not used in any
      cases. At the moment of receiving the infusion, all of the patients were
      receiving conventional treatment without any response, including inotropic
      support in 88 % of the cases. The administration of levosimendan was only
      suspended in one case due to the appearance of severe hypotension. In the rest of
      the administrations, it was well tolerated, without registering any severe side
      effect during the infusion process. Levosimendan proved to be a safe, effective
      strategy in our paediatric population. The good tolerance observed may be related
      to the absence of an initial bolus or loading dose.

PMID- 25608698
TI  - Feasibility of noninvasive fetal electrocardiographic monitoring in a clinical
      setting.
AB  - Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica
      AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality
      for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting.
      The fECG device has the ability to acquire fECG signals and allow calculation of
      fetal cardiac time intervals between 16- and 42-week gestational age (GA). We
      aimed to demonstrate the feasibility of fECG acquisition in a busy fetal
      cardiology clinic using the Monica fetal heart rate monitor. This is a
      prospective observational pilot study of fECG acquired from fetuses referred for
      fetal echocardiography. Recordings were performed for 5-15 min. Maternal signals
      were attenuated and fECG averaged. fECG and fetal cardiac time intervals (PR,
      QRS, RR, and QT) were evaluated by two cardiologists independently and inter
      observer reliability was assessed using intraclass coefficient (ICC). Sixty fECGs
      were collected from 50 mothers (mean GA 28.1 +/- 6.1). Adequate signal-averaged
      waveforms were obtained in 20 studies with 259 cardiac cycles. Waveforms could
      not be obtained between 26 and 30 weeks. Fetal cardiac time intervals were
      measured and were reproducible for PR (ICC = 0.89; CI 0.77-0.94), QRS (ICC =
      0.79; CI 0.51-0.91), and RR (ICC = 0.77; CI 0.53-0.88). QT ICC was poor due to
      suboptimal T-wave tracings. Acquisition of fECG and measurement of fetal cardiac
      time intervals is feasible in a clinical setting between 19- and 42-week GA,
      though tracings are difficult to obtain, especially between 26 and 30 weeks.
      There was high reliability in fetal cardiac time intervals measurements, except
      for QT. The device may be useful for assessing atrioventricular/intraventricular
      conduction in fetuses from 20 to 26 and >30 weeks. Techniques to improve signal
      acquisition, namely T-wave amplification, are ongoing.

PMID- 25608699
TI  - Vascular chronic Q fever: quality of life.
AB  - The aim of this study was to evaluate the quality of life in patients with
      vascular chronic Q fever at time of diagnosis and during follow-up. Based upon
      the SF-36 questionnaire, the mean physical and mental health of each patient were
      assessed at 3-month intervals for up to 18 months. A total of 26 patients were
      included in the study. At time of diagnosis, the mean physical health and mental
      health score was 50.6 [95% confidence interval (CI) 46.7-54.4] and 44.6 (95% CI
      41.6-47.5), respectively. During treatment, the mean physical health score
      declined significantly by 1.7 points each 3 months (P < 0.001) to 40.8 (95% CI
      34.4-45.1). The mean mental health score significantly and steadily increased
      towards 51.2 (95% CI 46.9-54.3) during follow-up (P = 0.026). A total of 23% of
      patients were cured after 18 months of follow-up. In conclusion, quality of life
      at time of diagnosis for patients with vascular chronic Q fever is lower compared
      to a similar group of patients, matched for age and gender, with an aortic
      abdominal aneurysmal disease, and physical health decreases further after
      starting treatment. Considering the low percentage of cure, the current treatment
      of vascular chronic Q fever patients may require a separate strategy from that of
      endocarditis in order to increase survival. 

PMID- 25608701
TI  - Outcomes improve in babies conceived by assisted reproduction, Nordic study
      shows.

PMID- 25608700
TI  - [The satisfied patient in aesthetic dermatology. Consensus work on patient
      satisfaction in botulinum toxin A treatment].
AB  - Patient satisfaction is an important factor for successful therapy. Many
      consensus reports have been published regarding correct treatment with botulinum
      toxin A (BTX-A). However, the focus of most of these publications has been on
      technical aspects and the important topic of patient satisfaction was often only
      one aspect among others. The Swiss Group of Esthetic Dermatology and Skincare
      (SGEDS) pursued these questions in a two-day consensus meeting. Patients of
      aesthetic dermatology are healthy and therefore place higher demands in contrast
      to ill patients of medical dermatology. This demands a great deal of the
      physician, the practice staff and the conditions in the practice to accommodate
      the special requirements of aesthetic clients. Informative consultation and
      patient education are of major importance; this also holds true for clinical
      performance and care before, during and after treatment with BTX-A. This
      publication aims at finding ways to gain greater patient satisfaction in daily
      practice. 

PMID- 25608702
TI  - How do we measure blood pressure at home?
AB  - BACKGROUND: Home blood pressure monitoring (HBPM) is one of the measures that
      increases compliance with antihypertensive therapy. HBPM requires a proper
      measurement technique as well as an accurate sphygmomanometer. The aim of this
      study was to assess the characteristics of home sphygmomanometers (HS) in a big
      city in Turkey. SUBJECTS AND METHOD: We assessed the HS of hypertensive patients
      (n = 452; male: 253, female: 199) who were examined for the first time in our
      outpatient center. General evaluation of HS included trademark, model, device's
      age, cuff size, validation and calibration status. RESULTS: We interviewed 452
      patients and 452 HS were identified. The most common factors affecting the
      patients' choice for the type and model of the HS were its simplicity and ease of
      use (28.2%), followed by advertisements (44%), physician's advice (19.3%) and the
      belief in accurate measurement (< 1%). All patients were unaware of validation
      and calibration of their devices. CONCLUSION: Awareness of both patients and
      physicians about the validation status of HS is not enough. Some complaints from
      patients may be associated with using non-validated HS. There is a need for a
      policy or standard criteria for HS.

PMID- 25608703
TI  - Histological appearance of anomalous anterior papillary muscle.

PMID- 25608705
TI  - Long-term stability study of Prussian blue-A quality assessment of water content
      and cyanide release.
AB  - CONTEXT: Prussian blue, ferric hexacyanoferrate is approved for (oral) treatment
      of internal contamination with radioisotopes of cesium or thallium. Cyanide makes
      up 35-40% of Prussian blue's molecular composition; thus, cyanide may be released
      during transit through the digestive tract under physiological pH conditions.
      OBJECTIVES: The purpose of this study is to assess the long-term stability of
      Prussian blue drug products and active pharmaceutical ingredients and its impact
      on cyanide release. The study involves the determination and comparison of the
      loss in water content and cyanide released from Prussian blue under pH conditions
      that bracket human physiological exposure. METHODS: Test samples of active
      pharmaceutical ingredient and drug product were stored for 10 years at ambient
      temperatures that mimic warehouse storage conditions. Water loss from Prussian
      blue was measured using thermogravimetric analysis. An in vitro physiological pH
      model that brackets gastric exposure and gastrointestinal transit was utilized
      for cyanide release. Prussian blue was incubated in situ at pH: 1.0, 5.0, and 7.0
      @ 37 degrees C for 1-24 h. Cyanide was measured using a validated colorimetric
      method by UV-Vis spectroscopy. RESULTS: Although the water content (quality
      attribute) of Prussian blue active pharmaceutical ingredient and drug product
      decreased by about 10.5% and 13.8%, respectively, since 2003, the cyanide release
      remained comparable. At pH of 7.0 for 24 h cyanide released from active
      pharmaceutical ingredient-1 was 21.33 +/- 1.76 MUg/g in 2004, and 28.45 +/- 3.15
      MUg/g in 2013; cyanide released from drug product-1 was 21.89 +/- 0.56 MUg/g in
      2004, and 27.31 +/- 5.78 MUg/g in 2013. At gastric pH of 1.0 and upper
      gastrointestinal pH of 5.0, the data for active pharmaceutical ingredients and
      drug products were also comparable in 2013. The cyanide release is still pH
      dependent and follows the same trend as observed in 2003 with minimum release at
      pH of 5.0 and maximal release at pH of 1.0. In summary, this is the long-term
      stability study of Prussian blue which correlates cyanide release to water loss.
      Cyanide released from Prussian blue was maximum at pH of 1.0 (47.47 MUg/g) and
      minimum at pH of 5.0-7.0 (20.01 MUg/g). CONCLUSIONS: Based on maximal dose,
      maximal residence time in stomach and intestine, the maximal cyanide released
      from Prussian blue is about 1.31 mg, which is far below the minimal lethal dose
      of cyanide of 50 mg, and therefore does not present a safety concern following
      long-term storage.

PMID- 25608704
TI  - Nested case-control studies: should one break the matching?
AB  - In a nested case-control study, controls are selected for each case from the
      individuals who are at risk at the time at which the case occurs. We say that the
      controls are matched on study time. To adjust for possible confounding, it is
      common to match on other variables as well. The standard analysis of nested case
      control data is based on a partial likelihood which compares the covariates of
      each case to those of its matched controls. It has been suggested that one may
      break the matching of nested case-control data and analyse them as case-cohort
      data using an inverse probability weighted (IPW) pseudo likelihood. Further, when
      some covariates are available for all individuals in the cohort, multiple
      imputation (MI) makes it possible to use all available data in the cohort. In the
      paper we review the standard method and the IPW and MI approaches, and compare
      their performance using simulations that cover a range of scenarios, including
      one and two endpoints. 

PMID- 25608706
TI  - Mesenteric inflammatory myofibroblastic tumors.
AB  - Inflammatory myofibroblastic tumors (IMTs), also known as inflammatory
      pseudotumors and inflammatory fibrosarcomas, are uncommon mesenchymal tumors
      composed of myofibroblastic spindle cells admixed with lymphocytes, plasma cells
      and eosinophils. Once thought to be reactive, these lesions are now considered to
      be neoplastic. These tumors can occur throughout the body, most commonly in the
      lung, mesentery and omentum. Patients commonly present with painless abdominal
      mass or with intestinal obstruction. IMTs may be multicentric, have a high local
      recurrence rate and may metastasize in rare cases. The lesions show wide
      variability in their histologic features and cellularity, and marked inflammatory
      infiltration, predominantly of plasmatocytes and lymphocytes, and occasionally
      neutrophils and eosinophils. Anaplastic lymphoma kinase (ALK) rearrangements
      and/or ALK1 and p80 immunoreactivity are reported in 33-67% of the tumors. Owing
      to the rarity of these lesions, there are no specific imaging findings that
      distinguish IMTs from other mesenteric masses. Complete surgical resection is the
      treatment of choice. Local recurrence rates are high, and re-excision is the
      preferred therapy for local recurrences. ALK-positive tumors show good response
      to ALK inhibitors. Current knowledge and comprehensive review of the available
      literature on IMTs is herein presented.

PMID- 25608708
TI  - Mapping thermomechanical pulp sludge (TMPS) biochar characteristics for
      greenhouse produce safety.
AB  - This study evaluates the existence of toxic compounds in thermomechanical pulp
      sludge (TMPS) derived biochars obtained through a slow pyrolysis process and
      establishes the criteria for manufacturing benign-quality biochar for safe
      greenhouse-based food production. Accordingly, nine TMPS biochars generated at
      different temperatures (450, 500, 550  degrees C) and residence times (30, 60,
      120 min) were investigated. Depending on the production conditions, the
      polycyclic aromatic hydrocarbons (PAHs) sum varied from 0.4 to 236 MUg/g biochar.
      Interestingly, correlations between the PAH content, toxicity, and process
      conditions were derived in the form of process toxicity relationships (PTRs). On
      the basis of the learning garnered in this study, it is recommended that TMPS
      feedstock will yield benign quality biochar when processed at a minimum 500 
      degrees C temperature for an optimum residence time of 30 min. 

PMID- 25608707
TI  - Pre- and post-sentence mental health service use by a population cohort of older
      offenders (>=45 years) in Western Australia.
AB  - PURPOSE: Information on older offenders' mental health service (MHS) used before
      and after sentence is sparse. We therefore aimed to determine the 1-year
      prevalence of MHS use before sentence, and the likelihood and predictors of MHS
      use in the 5-year post-sentence period by first-time older adult offenders (>=45
      years). METHODS: Pre- and post-sentence MHS use by a cohort of 1,853 first-time
      offenders over 45 years in Western Australia was determined through whole
      population linked administrative data. Logistic regression models compared the 1
      year pre-sentence MHS contacts between offenders and matched non-offenders. Cox
      proportional hazards regression models identified the socio-demographic,
      offending and pre-sentence health service variables that determined post-sentence
      MHS use. RESULTS: Older offenders were six times more likely to have used MHSs
      than non-offenders before sentence. Substance use was the most commonly treated
      disorder. Non-custodial offenders were twice more likely than prisoners to have
      been treated for any mental disorder and substance use disorders, and violent
      offenders were four times more likely to have attempted self-harm than non
      violent offenders before being sentenced. The strongest predictors of post
      sentence MHS contact were past psychiatric diagnosis in offenders with a pre
      sentence MHS contact, and pre-sentence hospitalisation for attempted self-harm or
      physical illness, or being a male in those without. Discontinuity in MHS use
      after sentence by over half of the offenders with a prior contact was prominent.
      CONCLUSION: Better detection and treatment of mental disorders in older offenders
      to ensure continuity of care at all transition points through age-sensitive
      correctional and community-based MHSs is needed.

PMID- 25608709
TI  - Inherent Driving Force for Charge Separation in Curved Stacks of Oligothiophenes.
AB  - Coexistence of high local charge mobility and an energy gradient can lead to
      efficient free charge carrier generation from geminate charge transfer states at
      the donor-acceptor interface in bulk heterojunction organic photovoltaics. It is,
      however, not clear what polymer microstructures can support such coexistence.
      Using recent methods from density functional theory, we propose that a stack of
      similarly curved oligothiophene chains can deliver the requirements for efficient
      charge separation. Curved stacks are stable because of the polymer's strong pi
      stacking ability and because backbone torsions are flexible in neutral chains.
      However, energy of a charge in a polymer chain has remarkably stronger dependence
      on torsions. The trend of increasing planarity in curved stacks effectively
      creates an energy gradient that drives charge in one direction. The curvature of
      these partially ordered stacks is found to beneficially interact with fullerenes
      for charge separation. The curved stacks, therefore, are identified as possible
      building blocks for interfacial structures that lead to efficient free carrier
      generation in high-performing organic photovoltaic systems. 

PMID- 25608710
TI  - Genetic and pharmacologic inhibition of eIF4E reduces breast cancer cell
      migration, invasion, and metastasis.
AB  - The translation initiation factor eIF4E is an oncogene that is commonly
      overexpressed in primary breast cancers and metastases. In this article, we
      report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and
      potently suppresses breast tumor formation. Ribavirin administration blocked the
      growth of primary breast tumors in several murine models and reduced the
      development of lung metastases in an invasive model. Mechanistically, eIF4E
      silencing or blockade reduced the invasiveness and metastatic capability of
      breast cancer cells in a manner associated with decreased activity of matrix
      metalloproteinase (MMP)-3 and MMP-9. Furthermore, eIF4E silencing or ribavirin
      treatment suppressed features of epithelial-to-mesenchymal transition, a process
      crucial for metastasis. Our findings offer a preclinical rationale to explore
      broadening the clinical evaluation of ribavirin, currently being tested in
      patients with eIF4E-overexpressing leukemia, as a strategy to treat solid tumors
      such as metastatic breast cancer.

PMID- 25608711
TI  - p21 ablation in liver enhances DNA damage, cholestasis, and carcinogenesis.
AB  - Genetic mouse studies suggest that the NF-kappaB pathway regulator NEMO (also
      known as IKKgamma) controls chronic inflammation and carcinogenesis in the liver.
      However, the molecular mechanisms explaining the function of NEMO are not well
      defined. Here, we report that overexpression of the cell-cycle regulator p21 is a
      critical feature of liver inflammation and carcinogenesis caused by the loss of
      NEMO. NEMO(Deltahepa) mice develop chronic hepatitis characterized by increased
      hepatocyte apoptosis and proliferation that causes the development of fibrosis
      and hepatocellular carcinoma (HCC), similar to the situation in human liver
      disease. Having identified p21 overexpression in this model, we evaluated its
      role in disease progression and LPS-mediated liver injury in double mutant
      NEMO(Deltahepa)/p21(-/-) mice. Eight-week-old NEMO(Deltahepa)/p21(-/-) animals
      displayed accelerated liver damage that was not associated with alterations in
      cell-cycle progression or the inflammatory response. However, livers from
      NEMO(Deltahepa)/p21(-/-) mice displayed more severe DNA damage that was further
      characterized by LPS administration correlating with higher lethality of the
      animals. This phenotype was attenuated by genetic ablation of the TNF receptor
      TNF-R1 in NEMO(Deltahepa)/p21(-/-) mice, demonstrating that DNA damage is induced
      via TNF. One-year-old NEMO(Deltahepa)/p21(-/-) mice displayed greater numbers of
      HCC and severe cholestasis compared with NEMO(Deltahepa) animals. Therefore, p21
      overexpression in NEMO(Deltahepa) animals protects against DNA damage,
      acceleration of hepatocarcinogenesis, and cholestasis. Taken together, our
      findings illustrate how loss of NEMO promotes chronic liver inflammation and
      carcinogenesis, and they identify a novel protective role for p21 against the
      generation of DNA damage.

PMID- 25608712
TI  - Multi-channel electronic and vibrational dynamics in polyatomic resonant high
      order harmonic generation.
AB  - High-order harmonic generation in polyatomic molecules generally involves
      multiple channels of ionization. Their relative contribution can be strongly
      influenced by the presence of resonances, whose assignment remains a major
      challenge for high-harmonic spectroscopy. Here we present a multi-modal approach
      for the investigation of unaligned polyatomic molecules, using SF6 as an example.
      We combine methods from extreme-ultraviolet spectroscopy, above-threshold
      ionization and attosecond metrology. Fragment-resolved above-threshold ionization
      measurements reveal that strong-field ionization opens at least three channels. A
      shape resonance in one of them is found to dominate the signal in the 20-26 eV
      range. This resonance induces a phase jump in the harmonic emission, a switch in
      the polarization state and different dynamical responses to molecular vibrations.
      This study demonstrates a method for extending high-harmonic spectroscopy to
      polyatomic molecules, where complex attosecond dynamics are expected.

PMID- 25608713
TI  - The use of FDG-PET in diffuse large B cell lymphoma (DLBCL): predicting outcome
      following first line therapy.
AB  - Positron emission tomography (PET) using 18fluoro-2-deoxyglucose (FDG) has become
      a standard clinical tool for staging and response assessment in aggressive
      lymphomas. The use of PET scans in clinical trials is still under exploration,
      however. In this review, we examine current data regarding PET in DLBCL, and its
      potential applicability to development of a surrogate endpoint to expedite
      clinical trial conduct. Interim PET scanning in DLBCL shows mixed results, with
      qualitative assessment variably associated with outcome. Addition of quantitative
      assessment might improve predictive power of interim scans. Data from multiple
      retrospective studies support that PET-defined response at end of treatment
      correlates with outcome in DLBCL. Optimal technical criteria for standardization
      of acquisition and criteria for interpretation of scans require further study.
      Prospective studies to define the correlation of PET-defined response and time
      dependent outcomes such as progression free survival (PFS) and overall survival
      (OS), critical for development of PET as a surrogate endpoint for clinical
      trials, are ongoing. In conclusion, evolving data regarding utility of PET in
      predictcing outcome of patients with DLBCL show promise to support the use of PET
      as a surrogate endpoint in clinical trials of DLBCL in the future.

PMID- 25608714
TI  - Urticaria due to polyethylene glycol-3350 and electrolytes for oral solution in a
      patient with jejunal nodular lymphoid hyperplasia.
AB  - Both jejunal nodular lymphoid hyperplasia (NLH) and polyethylene glycol (PEG)
      3350 hypersensitivity are extremely rare. We describe a 30-year-old female who
      had previously taken a PEG-3350 bowel preparation without adverse effects, and
      presented for evaluation of chronic diarrhea. An upper and lower gastrointestinal
      endoscopy, and small bowel series were scheduled. PEG-3350 and electrolytes for
      oral solution was prescribed for bowel cleansing. During consumption of the bowel
      preparation she developed urticarial hypersensitivity. An alternative bowel
      preparation was used. Colonoscopy and upper endoscopy were normal, but small
      bowel series revealed innumerable sand-like lucencies in the jejunum. NLH was
      confirmed on biopsy from antegrade enteroscopy. This is the first case report on
      the pathological jejunal NLH in association with the PEG-3350 urticarial
      hypersensitivity. The potential pathophysiological etiology of this association
      is discussed.

PMID- 25608717
TI  - Metal-organic frameworks catalyzed C-C and C-heteroatom coupling reactions.
AB  - Metal organic frameworks (MOFs) are porous crystalline solids whose structure is
      formed by metal ions or clusters of a few metal ions held in place by bi- or
      multipodal organic linkers. In some cases, the metal nodes in MOFs have
      exchangeable coordination positions that allow them to participate as active
      sites promoting organic reactions. There is much current interest in exploiting
      the advantages that MOFs offer as catalysts, including a large surface area, high
      metal content, flexibility in the design of the active sites in the framework,
      together with the easy synthesis of these materials. In the present review we
      describe the use of MOFs as catalysts to promote cross-coupling reactions
      involving organometallic reaction intermediates and catalysis by Lewis acid
      sites. These types of reactions are of large synthetic utility due to the high
      yields achieved, mild conditions and compatibility with other functional groups.
      The content includes C-C bond forming reactions, such as Suzuki-Miyaura, Mizoroki
      Heck, Sonogashira, Stille and Ullmann, but also C-O and C-N cross-couplings. The
      final section summarizes our views on future developments and targets in these
      types of reactions. The core of the review is references that have appeared in
      2010 or after, which give an idea of the novelty and current interest in this
      area. 

PMID- 25608718
TI  - A scalable method to concentrate lentiviral vectors pseudotyped with measles
      virus glycoproteins.
AB  - Lentiviral (LV) vectors have emerged as powerful tools for basic research and
      clinical applications because of their ability to stably transduce both dividing
      and nondividing cells. A wide range of viral envelope (Env) glycoproteins have
      the ability to associate with the membrane of LV vectors, a process that is
      referred to as pseudotyping. Pseudotyped vectors have the capacity to transduce
      specific cell types for specific applications. For example, LV vectors
      pseudotyped with the measles virus (MV)-derived hemagglutinin (H) and fusion (F)
      proteins have the ability to transduce quiescent lymphocytes. In addition, the MV
      H glycoprotein can be engineered allowing cell-specific targeting of LV vectors.
      One problem with MV glycoprotein-pseudotyped LV vectors is low titer during
      vector production. This results in the need to manufacture large volumes of the
      vectors and to concentrate them to appropriate titers. The commonly used
      centrifugation-based concentration techniques for LV vectors are not practical
      for large-scale vector manufacturing. Thus, there is a need for improved methods
      to concentrate LV vectors. In this study, we adapted an anion-exchange membrane
      chromatography method that we previously used in the context of LV vectors
      pseudotyped with the vesicular stomatitis virus glycoprotein to concentate MV
      glycoprotein-pseudotyped LV vectors. Up to 60% of the input vectors with an up to
      5300-fold reduction in volume was achieved using this anion-exchange
      chromatography method in conjunction with a desalting/concentration step
      involving centrifugal filter units. This technique provides a rapid and scalable
      approach for concentrating MV-pseudotyped LV vectors that does not require an
      elaborate setup. 

PMID- 25608720
TI  - Surface enhanced vibrational spectroscopic evidence for an alternative DNA
      independent redox activation of endonuclease III.
AB  - Surface enhanced vibrational spectro-electrochemistry of endonuclease III
      provides direct evidence that the [4Fe-4S] cluster is responsible for the enzyme
      redox activity, and that this process is not exclusively DNA-mediated, as
      currently proposed. We report the first surface enhanced resonance Raman spectrum
      of a [4Fe-4S](2+) cluster containing enzyme. 

PMID- 25608719
TI  - Comprehension of Randomization and Uncertainty in Cancer Clinical Trials Decision
      Making Among Rural, Appalachian Patients.
AB  - Comprehension of randomization is a vital, but understudied, component of
      informed consent to participate in cancer randomized clinical trials (RCTs). This
      study examines patient comprehension of the randomization process as well as
      sources of ongoing uncertainty that may inhibit a patient's ability to provide
      informed consent to participate in RCTs. Cancer patients living in rural
      Appalachia who were offered an opportunity to participate in a cancer treatment
      RCT completed in-depth interviews and a brief survey. No systematic differences
      in randomization comprehension between patients who consented and those who
      declined participation in a cancer RCT were detected. Comprehension is
      conceptually distinct from uncertainty, with patients who had both high and low
      comprehension experiencing randomization-related uncertainty. Uncertainty about
      randomization was found to have cognitive and affective dimensions. Not all
      patients enrolling in RCTs have a sufficient understanding of the randomization
      process to provide informed consent. Healthcare providers need to be aware of the
      different types of randomization-related uncertainty. Efforts to improve informed
      consent to participate in RCTs should focus on having patients teach back their
      understanding of randomization. This practice could yield valuable information
      about the patient's cognitive and affective understanding of randomization as
      well as opportunities to correct misperceptions. Education about RCTs should
      reflect patient expectations of individualized care by explaining how all
      treatments being compared are appropriate to the specifics of a patient's
      disease. 

PMID- 25608721
TI  - A critical assessment of the methodologies to investigate the role of inhibition
      of apoptosis in rodent hepatocarcinogenesis.
AB  - Non-genotoxic carcinogens act by promoting the clonal expansion of preneoplastic
      cells by directly or indirectly stimulating cell division or inhibiting cell loss
      in the target organ. The specific mode-of-action (MoA) by which some non
      genotoxic carcinogens ultimately cause cancer is not completely understood. To
      date, there are several proposed MoAs for non-genotoxic carcinogens, and some of
      these propose inhibition of apoptosis as one of the key events. In general,
      inhibition of apoptosis is considered a necessary step for cell survival and in
      theory can occur in combination or in association with other key promotional
      events, such as cell proliferation, oxidative stress and inhibition of
      intercellular communication to promote carcinogenesis. However, the evidence
      supporting the role of inhibition of apoptosis as a necessary step in promoting
      specific chemically induced tumors is often debated. To address this evidence, we
      reviewed studies that utilized prototypical nuclear receptor-mediated
      hepatocarcinogens. Based on this review, it is proposed that the ability to
      determine the importance of inhibition of apoptosis as a key event in the MoA for
      tumor promotion is hampered by the limitations of the methods utilized for its
      detection. This review provides an assessment of the strengths and limitations of
      the current methodology used for detection of apoptosis and provides suggestions
      for improving its detection, thereby strengthening the weight of evidence
      supporting inhibition of apoptosis as a key event in a MoA for tumor promotion. 

PMID- 25608722
TI  - Photoimmunology and Multiple Sclerosis.
AB  - The ultraviolet (UV) radiation contained in sunlight is a powerful immune
      suppressant. While exposure to UV is best known for its ability to cause skin
      cancer, it is also associated with protection against a range of autoimmune
      diseases, particularly multiple sclerosis (MS). Although the precise mechanism by
      which sunlight affords protection from MS remains to be determined, some have
      hypothesised that UV immunosuppression explains the "latitude-gradient effect"
      associated with MS. By stimulating the release of soluble factors in exposed
      skin, UV activates immune suppressive pathways that culminate in the induction of
      regulatory cells in distant tissues. Each and every one of the immune suppressive
      cells and molecules activated by UV exposure are potential targets for treating
      and preventing MS. A thorough understanding of the mechanisms involved is
      therefore required if we are to realise the therapeutic potential of
      photoimmunology. 

PMID- 25608724
TI  - Structural insight into the active site of a Bombyx mori unclassified glutathione
      transferase.
AB  - Glutathione transferases (GSTs) are major detoxification enzymes that play
      central roles in the defense against various environmental toxicants as well as
      oxidative stress. Here, we identify amino acid residues of an unclassified GST
      from Bombyx mori, bmGSTu-interacting glutathione (GSH). Site-directed mutagenesis
      of bmGSTu mutants indicated that amino acid residues Asp103, Ser162, and Ser166
      contribute to catalytic activity. 

PMID- 25608725
TI  - Marine structure derived calcium phosphate-polymer biocomposites for local
      antibiotic delivery.
AB  - Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with
      medically active substances were used to develop polylactic acid (PLA) thin film
      composites for slow drug delivery systems. The effects of HAp particles within
      PLA matrix on the gentamicin (GM) release and release kinetics were studied. The
      gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model
      with mainly diffusional process with a number of different drug transport
      mechanisms. Statistical analysis shows very significant difference on the release
      of gentamicin between GM containing PLA (PLAGM) and GM containing HAp
      microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower
      release rates. The use of HAp particles improved drug stabilization and higher
      drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for
      the regeneration and repair of diseased bone tissue. The release profiles,
      exhibited a steady state release rate with significant antimicrobial activity
      against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of
      bacteria. The devices also indicated significant ability to control the growth of
      bacterial even after four weeks of drug release. Clinical release profiles can be
      easily tuned from drug-HAp physicochemical interactions and degradation kinetics
      of polymer matrix. The developed systems could be applied to prevent microbial
      adhesion to medical implant surfaces and to treat infections mainly caused by S.
      aureus in surgery. 

PMID- 25608723
TI  - Sleep and plasticity in schizophrenia.
AB  - Schizophrenia is a devastating mental illness with a worldwide prevalence of
      approximately 1%. Although the clinical features of the disorder were described
      over one hundred years ago, its neurobiology is still largely elusive despite
      several decades of research. Schizophrenia is associated with marked sleep
      disturbances and memory impairment. Above and beyond altered sleep architecture,
      sleep rhythms including slow waves and spindles are disrupted in schizophrenia.
      In the healthy brain, these rhythms reflect and participate in plastic processes
      during sleep. This chapter discusses evidence that schizophrenia patients exhibit
      dysfunction of sleep-mediated plasticity on a behavioral, cellular, and molecular
      level and offers suggestions on how the study of sleeping brain activity can shed
      light on the pathophysiological mechanisms of the disorder.

PMID- 25608726
TI  - Squid pen chitin chitooligomers as food colorants absorbers.
AB  - One of the most promising applications of chitosanase is the conversion of
      chitinous biowaste into bioactive chitooligomers (COS). TKU033 chitosanase was
      induced from squid pen powder (SPP)-containing Bacillus cereus TKU033 medium and
      purified by ammonium sulfate precipitation and column chromatography. The enzyme
      was relatively more thermostable in the presence of the substrate and had an
      activity of 93% at 50  degrees C in a pH 5 buffer solution for 60 min.
      Furthermore, the enzyme used for the COS preparation was also studied. The enzyme
      products revealed various mixtures of COS that with different degrees of
      polymerization (DP), ranging from three to nine. In the culture medium, the
      fermented SPP was recovered, and it displayed a better adsorption rate (up to
      96%) for the disperse dyes than the water-soluble food colorants, Allura Red AC
      (R40) and Tartrazne (Y4). Fourier transform-infrared spectroscopic (FT-IR)
      analysis proved that the adsorption of the dyes onto fermented SPP was a physical
      adsorption. Results also showed that fermented SPP was a favorable adsorber and
      could be employed as low-cost alternative for dye removal in wastewater
      treatment. 

PMID- 25608727
TI  - Influences on and patterns in total gaseous mercury (TGM) at Harwell, England.
AB  - Total gaseous mercury (TGM) was monitored during 2013 at the rural monitoring
      site, Harwell, England using the Tekran 2537A monitoring system. Average TGM for
      the year was 1.45 +/- 0.24 ng m(-3). This is comparable to other northern
      hemisphere studies, but on average 0.5 ng m(-3) higher than at its sister
      monitoring station at Auchencorth Moss, Scotland, but 14% lower than that found
      in a similar study at the same location of 1.68 ng m(-3) in 1995/6. Using wind
      sector analysis we show the important influence of local emissions, with our data
      showing that the largest influence on TGM observed is that of the adjacent
      Science & Innovation campus, making the site more a 'suburban background'. By
      using co-located measurements of black carbon and sulphur dioxide as tracers, we
      present an initial investigation into the impact of the closure of Didcot A coal
      fired power station, which ceased operating in March 2013. Further analysis using
      air mass back trajectories shows the long-range contribution to TGM from
      continental Europe, and that the lowest levels are associated with marine air
      masses from the west. 

PMID- 25608728
TI  - Trajectories of multimorbidity: exploring patterns of multimorbidity in patients
      with more than ten chronic health problems in life course.
AB  - BACKGROUND: Physicians are frequently confronted with complex health situations
      of patients, but knowledge of intensive forms of multimorbidity and their
      development during life is lacking. This study explores patterns and trajectories
      of chronic health problems of patients with multimorbidity particularly those
      with more than ten conditions and type and variety of organ systems involved in
      these patterns during life. METHOD: Life time prevalence patterns of chronic
      health problems were determined in patients with illness trajectories
      accumulating more than ten chronic health problems during life as registered by
      general practitioners in the South of the Netherlands in the Registration Network
      Family Practices (RNH). RESULTS: Overall 4,560 subjects (5%) were registered with
      more than ten chronic health problems during their life (MM11+), accounting for
      61,653 (20%) of the 302,808 registered health problems in the population (N =
      87,837 subjects). More than 30% accumulates 4 or more chronic health conditions
      (MM4-5: 4-5 conditions (N = 14,199; 16.2%); MM6-10: 6-10 conditions (N = 14,365;
      16.4%). Gastro-intestinal, cardiovascular, locomotor, respiratory and metabolic
      conditions occur more frequently in the MM11+ patients than in the other
      patients, while the nature and variety of body systems involved in lifetime
      accumulation of chronic health problem clusters is both generic and specific.
      Regarding chronic conditions afflicting multiple sites throughout the body, the
      number of neoplasms seems low (N = 3,592; 5.8%), but 2,461 (49%) of the 4,560
      subjects have registered at least one neoplasm condition during life. A similar
      pattern is noted for inflammation (N = 3,537, 78%), infection (N = 2,451, 54%)
      and injury (N = 3,401, 75%). CONCLUSION: There are many challenges facing
      multimorbidity research, including the implementation of a longitudinal, life
      time approach from a family practice perspective. The present study, although
      exploratory by nature, shows that both general and specific mechanisms
      characterize the development of multimorbidity trajectories. A small proportion
      of patients has a high number of chronic health problems (MM11+) and keeps adding
      health problems during life. However, GP's need to realise that more than one
      third of their patients accumulate four or more chronic health problems (MM4-5
      and MM6-10) during life.

PMID- 25608729
TI  - WS2 mode-locked ultrafast fiber laser.
AB  - Graphene-like two dimensional materials, such as WS2 and MoS2, are highly
      anisotropic layered compounds that have attracted growing interest from basic
      research to practical applications. Similar with MoS2, few-layer WS2 has
      remarkable physical properties. Here, we demonstrate for the first time that WS2
      nanosheets exhibit ultrafast nonlinear saturable absorption property and high
      optical damage threshold. Soliton mode-locking operations are achieved separately
      in an erbium-doped fiber laser using two types of WS2-based saturable absorbers,
      one of which is fabricated by depositing WS2 nanosheets on a D-shaped fiber,
      while the other is synthesized by mixing WS2 solution with polyvinyl alcohol, and
      then evaporating them on a substrate. At the maximum pump power of 600 mW, two
      saturable absorbers can work stably at mode-locking state without damage,
      indicating that few-layer WS2 is a promising high-power flexible saturable
      absorber for ultrafast optics. Numerous applications may benefit from the
      ultrafast nonlinear features of WS2 nanosheets, such as high-power pulsed laser,
      materials processing, and frequency comb spectroscopy. 

PMID- 25608730
TI  - Prospects of nanoscience with nanocrystals.
AB  - Colloidal nanocrystals (NCs, i.e., crystalline nanoparticles) have become an
      important class of materials with great potential for applications ranging from
      medicine to electronic and optoelectronic devices. Today's strong research focus
      on NCs has been prompted by the tremendous progress in their synthesis.
      Impressively narrow size distributions of just a few percent, rational shape
      engineering, compositional modulation, electronic doping, and tailored surface
      chemistries are now feasible for a broad range of inorganic compounds. The
      performance of inorganic NC-based photovoltaic and light-emitting devices has
      become competitive to other state-of-the-art materials. Semiconductor NCs hold
      unique promise for near- and mid-infrared technologies, where very few
      semiconductor materials are available. On a purely fundamental side, new insights
      into NC growth, chemical transformations, and self-organization can be gained
      from rapidly progressing in situ characterization and direct imaging techniques.
      New phenomena are constantly being discovered in the photophysics of NCs and in
      the electronic properties of NC solids. In this Nano Focus, we review the state
      of the art in research on colloidal NCs focusing on the most recent works
      published in the last 2 years. 

PMID- 25608731
TI  - Effects of particle size and drying methods of corn on growth performance,
      digestibility and haematological and immunological characteristics of weaned
      piglets.
AB  - The objective of this study was to evaluate the effects of particle size and
      drying methods of corn on growth performance of weaned piglets. Crossbreed weaned
      piglets (n = 192; Duroc * Landrace * Large White) were assigned to one of four
      treatments (2 * 2 factorial arrangement). All piglets were fed corn-soybean meal
      diets and treatments were (1) hot air-dried and coarsely ground corn, (2) hot air
      dried and finely ground corn, (3) sun-dried and coarsely ground corn and (4) sun
      dried and finely ground corn. The results showed that finely ground corn (FGC)
      improved the performance of piglets. Additionally, the apparent total tract
      digestibility (ATTD) of gross energy (GE) and ether extract (EE) were increased
      by FGC, but the drying methods did not affect the performance of piglets or ATTD.
      Furthermore, smaller particle size significantly decreased the intestinal
      permeability, which was also not influenced by drying methods. FGC increased the
      total number of white blood cells, but not other blood parameters. Finally, the
      level of serum interleukin-1 was decreased by fine grinding and that of serum
      tumour necrosis factor alpha was decreased by sun drying. Conversely, these
      characteristics of weaned piglets can hardly have been affected either by the
      corn drying method or its interaction with grinding methods.

PMID- 25608733
TI  - Gaps in smiles and services: a cross-sectional study of dental caries in refugee
      background children.
AB  - BACKGROUND: Refugees are reported to experience high rates of dental disease,
      although there are limited data on refugee children. The aim of this study was to
      report on oral health in refugee-background children in Australia, and to assess
      their follow-up at dental services. METHODS: Cross-sectional study of
      opportunistic oral health screening and subsequent dental service use in refugee
      background children attending a refugee health clinic in Victoria, Australia,
      between November 2006-November 2010. RESULTS: 350 patients (0-18 years, mean age
      8 years 7 months) had oral health screening; 241 (68.9%) were born overseas, (176
      Africa, 65 other countries) and 109 (31.1%) were born in Australia to African
      background families. Parents were concerned about oral health in 65/341 (19.1%)
      children, with specific concern about caries in only 9/341 (2.6%). On assessment,
      155/336 (46.1%) had visible caries and 178/345 (51.6%) had caries experience
      (dmft/DMFT > 0). Where parents were concerned about caries, they were likely to
      be present (positive predictive value = 100%), however absence of parent concern
      about caries was not reassuring (negative predictive value = 56.1%).Compared to
      Australian-born children of African background; African-born children were more
      likely to be referred for further dental care (adjusted PR 1.33, 95% CI [1.02
      1.73]), although there was no statistically significant difference in caries
      prevalence. African-born children were less likely to have caries compared to
      other overseas-born children (adjusted PR 0.73, 95% CI [0.58 - 0.93]). Overall
      187/344 (54.4%) children were referred for further dental care; 91/124 (73.4%)
      attended any dental appointment. Attendance rates were 90% with a phone reminder
      system for appointments, attendance reduced when this system lapsed. CONCLUSIONS:
      Oral health is an important public health issue in refugee-background children,
      despite low levels of parent concern and very few parent reported caries. Routine
      direct oral health assessment is important in refugee-background children and co
      ordinated health systems may help improve their attendance at dental services.

PMID- 25608734
TI  - Implementing healthy lifestyle promotion in primary care: a quasi-experimental
      cross-sectional study evaluating a team initiative.
AB  - BACKGROUND: Non-communicable diseases are a leading cause of death and can
      largely be prevented by healthy lifestyles. Health care organizations are
      encouraged to integrate healthy lifestyle promotion in routine care. This study
      evaluates the impact of a team initiative on healthy lifestyle promotion in
      primary care. METHODS: A quasi-experimental, cross-sectional design compared
      three intervention centres that had implemented lifestyle teams with three
      control centres that used a traditional model of care. Outcomes were defined
      using the RE-AIM framework: reach, the proportion of patients receiving lifestyle
      promotion; effectiveness, self-reported attitudes and competency among staff;
      adoption, proportion of staff reporting regular practice of lifestyle promotion;
      implementation, fidelity to the original lifestyle team protocol. Data collection
      methods included a patient questionnaire (n = 888), a staff questionnaire (n =
      120) and structured interviews with all practice managers and, where applicable,
      team managers (n = 8). The chi square test and problem-driven content analysis
      was used to analyse the questionnaire and interview data, respectively. RESULTS:
      Reach: patients at control centres (48%, n = 211) received lifestyle promotion
      significantly more often compared with patients at intervention centres (41%, n =
      169). Effectiveness: intervention staff was significantly more positive towards
      the effectiveness of lifestyle promotion, shared competency and how lifestyle
      promotion was prioritized at their centre. Adoption: 47% of staff at intervention
      centres and 58% at control centres reported that they asked patients about their
      lifestyle on a daily basis. IMPLEMENTATION: all intervention centres had
      implemented multi-professional teams and team managers and held regular meetings
      but struggled to implement in-house referral structures for lifestyle promotion,
      which was used consistently among staff. CONCLUSIONS: Intervention centres did
      not show higher rates than control centres on reach of patients or adoption among
      staff at this stage. All intervention centres struggled to implement working
      referral structures for lifestyle promotion. Intervention centres were more
      positive on effectiveness outcomes, attitudes and competency among staff,
      however. Thus, lifestyle teams may facilitate lifestyle promotion practice in
      terms of increased responsiveness among staff, illustrated by positive attitudes
      and perceptions of shared competency. More research is needed on lifestyle
      promotion referral structures in primary care regarding their configuration and
      implementation.

PMID- 25608735
TI  - Prognostic factors in advanced pharyngeal and oral cavity cancer; significance of
      multimodality imaging in terms of 7th edition of TNM.
AB  - As with most cancers the prognosis in pharyngeal and oral cavity cancer largely
      depends on tumour stage. Physical examination, including endoscopy should be
      combined with technical radiologic imaging to record the precise extent of
      tumour. The TNM staging system of the head and neck region is, in fact, an
      anatomic staging system that describes the anatomic extent of the primary tumour
      as well as the involvement of regional lymph nodes and distant metastases.
      Modifications in the TNM staging system should consider not only the expert
      opinions and published reports in the literature but the technical advances in
      technology for improved assessment of tumour extent and the shifting paradigms in
      therapeutic strategies. "T" stage of the tumour is defined by its size, the depth
      of the invasion and the involvement of vital structures. In the 7th edition of
      TNM classification, for stage T4 tumors (larger than 4 cm), subcategories a and b
      were introduced to indicate the involvement of vital structures and their
      suitability for surgical resection (except for nasopharynx cancer). Nodal
      metastasis is the most important predictor of outcome for squamous cell cancer of
      the head and neck. 

PMID- 25608736
TI  - Uterine rupture disguised by urinary retention following a second trimester
      induced abortion: a case report.
AB  - BACKGROUND: Uterine rupture classically presents with severe abdominal pain, loss
      of fetal station, vaginal bleeding, and shock. CASE PRESENTATION: We present a
      case of uterine rupture presenting as significant urinary retention that occurred
      following a second trimester abortion induced with mifepristone and misoprostol.
      Uterine rupture was discovered unexpectedly on diagnostic laparoscopy. The
      uterine rupture was contained by dense adhesions between the omentum and bladder
      with the previous uterine cesarean hysterotomy scar. CONCLUSION: This case
      highlights the difficulties in diagnosis of abnormal placentation and an unusual
      presentation of uterine rupture. This case was managed successfully
      laparoscopically.

PMID- 25608737
TI  - Cloud computing approaches for prediction of ligand binding poses and pathways.
AB  - We describe an innovative protocol for ab initio prediction of ligand
      crystallographic binding poses and highly effective analysis of large datasets
      generated for protein-ligand dynamics. We include a procedure for setup and
      performance of distributed molecular dynamics simulations on cloud computing
      architectures, a model for efficient analysis of simulation data, and a metric
      for evaluation of model convergence. We give accurate binding pose predictions
      for five ligands ranging in affinity from 7 nM to > 200 MUM for the immunophilin
      protein FKBP12, for expedited results in cases where experimental structures are
      difficult to produce. Our approach goes beyond single, low energy ligand poses to
      give quantitative kinetic information that can inform protein engineering and
      ligand design. 

PMID- 25608738
TI  - Dynamic HypA zinc site is essential for acid viability and proper urease
      maturation in Helicobacter pylori.
AB  - Helicobacter pylori requires urease activity in order to survive in the acid
      environment of the human stomach. Urease is regulated in part by nickelation, a
      process that requires the HypA protein, which is a putative nickel
      metallochaperone that is generally associated with hydrogenase maturation.
      However, in H. pylori, HypA plays a dual role. In addition to an N-terminal
      nickel binding site, HypA proteins also contain a structural zinc site that is
      coordinated by two rigorously conserved CXXC sequences, which in H. pylori are
      flanked by His residues. These structural Zn sites are known to be dynamic,
      converting from Zn(Cys)4 centers at pH 7.2 to Zn(Cys)2(His)2 centers at pH 6.3 in
      the presence of Ni(ii) ions. In this study, mutant strains of H. pylori that
      express zinc site variants of the HypA protein are used to show that the
      structural changes in the zinc site are important for the acid viability of the
      bacterium, and that a reduction in acid viability in these variants can be traced
      in large measure to deficient urease activity. This in turn leads to a model that
      connects the Zn(Cys)4 coordination to urease maturation. 

PMID- 25608740
TI  - Renal Cell Carcinoma Presenting with Paraneoplastic Hallucinations and Cognitive
      Decline from Limbic Encephalitis.
AB  - We present a 66-year-old woman with 2 months of visual hallucinations,
      unintentional weight loss, and short-term memory decline, whose clinical
      presentation and EEG supported a diagnosis of limbic encephalitis. Subsequent
      evaluation for a paraneoplastic etiology revealed a renal mass, which was
      resected and identified as clear cell renal carcinoma. The patient's clinical
      condition improved after resection of the mass. When patients present with
      incongruous subacute neuropsychiatric symptoms, clinicians should be mindful of
      paraneoplastic neurological disorders, as early diagnosis and treatment of
      malignancy may lead to symptomatic improvement.

PMID- 25608739
TI  - Increased cardiovascular disease, resource use, and costs before the clinical
      diagnosis of diabetes in veterans in the southeastern U.S.
AB  - IMPORTANCE: Screening for diabetes might be more widespread if adverse
      associations with cardiovascular disease (CVD), resource use, and costs were
      known to occur earlier than conventional clinical diagnosis. OBJECTIVE: The
      purpose of this study was to determine whether adverse effects associated with
      diabetes begin prior to clinical diagnosis. DESIGN: Veterans with diabetes were
      matched 1:2 with controls by follow-up, age, race/ethnicity, gender, and VA
      facility. CVD was obtained from ICD-9 codes, and resource use and costs from VA
      datasets. SETTING: VA facilities in SC, GA, and AL. PARTICIPANTS: Patients with
      and without diagnosed diabetes. MAIN OUTCOME MEASURES: Diagnosed CVD, resource
      use, and costs. RESULTS: In this study, the 2,062 diabetic patients and 4,124
      controls were 63 years old on average, 99 % male, and 29 % black; BMI was 30.8 in
      diabetic patients vs. 27.8 in controls (p<0.001). CVD prevalence was higher and
      there were more outpatient visits in Year -4 before diagnosis through Year +4
      after diagnosis among diabetic vs. control patients (all p<0.01); in Year -2, CVD
      prevalence was 31 % vs. 24 %, and outpatient visits were 22 vs. 19 per year,
      respectively. Total VA costs/year/veteran were higher in diabetic than control
      patients from Year -4 ($4,083 vs. $2,754) through Year +5 ($8,347 vs. $5,700)
      (p<0.003) for each, reflecting underlying increases in outpatient, inpatient, and
      pharmacy costs (p<0.05 for each). Regression analysis showed that diabetes
      contributed an average of $1,748/year to costs, independent of CVD (p<0.001).
      CONCLUSIONS AND RELEVANCE: VA costs per veteran are higher--over $1,000/year
      before and $2,000/year after diagnosis of diabetes--due to underlying increases
      in outpatient, inpatient, and pharmacy costs, greater number of outpatient
      visits, and increased CVD. Moreover, adverse associations with veterans' health
      and the VA healthcare system occur early in the natural history of the disease,
      several years before diabetes is diagnosed. Since adverse associations begin
      before diabetes is recognized, greater consideration should be given to
      systematic screening in order to permit earlier detection and initiation of
      preventive management. Keeping frequency of CVD and marginal costs in line with
      those of patients before diabetes is currently diagnosed has the potential to
      save up to $2 billion a year.

PMID- 25608741
TI  - Capsule Commentary on Bell et al., Impact of a Randomized Control Educational
      Trial to Improve Physician Practice Behaviors Around Screening for Inherited
      Breast Cancer.

PMID- 25608742
TI  - Comparative effectiveness of three anxiolytics for acute respiratory infections:
      antibiotics, C-reactive protein point-of-care testing, and improved
      communication.

PMID- 25608743
TI  - The pace of change in medical practice and health policy: collision or
      coexistence?
AB  - Medical practice and health policy are both changing rapidly. While the adopting
      of changes is not new for physicians, the pace of change in standards of care,
      marked by advances and reversals, has accelerated over the course of the past
      decade. A recurring new theme in medical practice has been an emphasis on
      tailoring treatment plans to individual patients. Physicians have had to
      simultaneously absorb new processes in the health care system brought about by
      the Health Information Technology for Economic and Clinical Health (HITECH) Act
      in 2009 and the Affordable Care Act (ACA) in 2010. The ability of physicians to
      maintain standards of care that focus on individual patients may conflict with
      changes resulting from new health policies that emphasize population health
      management. Primary care physicians may be one of the few collective voices
      capable of identifying areas where population-level health policies conflict with
      the care of individual patients, and policymakers should include practicing
      primary care physicians in the form of community boards in order to ensure the
      development of new health policies that provide sustainable high-value patient
      care. 

PMID- 25608744
TI  - Direct to consumer advertising: the case for greater consumer control.

PMID- 25608745
TI  - Plasmids are vectors for redundant chromosomal genes in the Bacillus cereus
      group.
AB  - BACKGROUND: Prokaryotic plasmids have played significant roles in the evolution
      of bacterial genomes and have a great impact on the metabolic functions of the
      host cell. Many bacterial strains contain multiple plasmids, but the
      relationships between bacterial plasmids and chromosomes are unclear. We focused
      on plasmids from the Bacillus cereus group because most strains contain several
      plasmids. RESULTS: We collected the genome sequences of 104 plasmids and 20
      chromosomes from B. cereus group strains, and we studied the relationships
      between plasmids and chromosomes by focusing on the pan-genomes of these plasmids
      and chromosomes. In terms of basic features (base composition and codon usage),
      the genes on plasmids were more similar to the chromosomal variable genes
      (distributed genes and unique genes) than to the chromosomal core genes. Although
      all the functional categories of the chromosomal genes were exhibited by the
      plasmid genes, the proportions of each category differed between these two gene
      sets. The 598 gene families shared between chromosomes and plasmids displayed a
      uniform distribution between the two groups. A phylogenetic analysis of the
      shared genes, including the chromosomal core gene set, indicated that gene
      exchange events between plasmids and chromosomes occurred frequently during the
      evolutionary histories of the strains and species in this group. Moreover, the
      shared genes between plasmids and chromosomes usually had different promoter and
      terminator sequences, suggesting that they are regulated by different elements at
      the transcriptional level. CONCLUSIONS: We speculate that for the entire B.
      cereus group, adaptive genes are preserved on both plasmids and chromosomes;
      however, in a single cell, homologous genes on plasmids and the chromosome are
      controlled by different regulators to reduce the burden of maintaining redundant
      genes.

PMID- 25608746
TI  - Active and latent tuberculosis in Brazilian correctional facilities: a cross
      sectional study.
AB  - BACKGROUND: Tuberculosis (TB) rates among prisoners are more than 20 times that
      of the general population in Brazil, yet there are limited data available to
      facilitate the development of effective interventions in this high-transmission
      setting. We aimed to assess risk factors for TB infection and evaluate the yield
      of mass screening for active disease among inmates. METHODS: We administered a
      questionnaire and tuberculin skin test (TST) to a population-based sample of
      inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing
      and two sputum samples for smear microscopy and culture from participants
      reporting a cough of any duration. Hierarchical Poisson regression models were
      used to evaluate factors associated with latent tuberculosis infection (LTBI).
      RESULTS: We recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8
      prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%)
      subjects who reported a cough, we obtained sputum from 691 (68%) and identified
      31 cases of active TB for a point prevalence of 917 (95% CI, 623-1302) per
      100,000 prisoners. Evaluation of the two sputum smear samples failed to identify
      74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms.
      Obtaining a second culture identified an additional 7 (24%) cases. The
      prevalences of LTBI were 22.5% and 11.7% for male and female prisoners,
      respectively and duration of incarceration (in years) was associated with LTBI in
      male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95%
      CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly
      incarcerated inmates, among whom LTBI prevalence significantly increased by 5%
      with each year of incarceration. CONCLUSIONS: Although the overall LTBI
      prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is
      high (>1,800/100,00), likely due to the high force of infection among a largely
      susceptible inmate population. Efforts to reduce transmission in prisons may
      require mass screening for active TB, utilizing sputum culture in case-detection
      protocols.

PMID- 25608747
TI  - Differences in patient outcomes after conventional versus real time perfusion
      stress echocardiography in men versus women: a prospective randomised trial.
AB  - OBJECTIVE: The purpose of our study was to determine whether sex affects the
      predictive value of perfusion and wall motion imaging obtained with real time
      myocardial contrast echocardiography (RTMCE) when compared with conventional
      stress echocardiography (CSE). METHODS: We prospectively enrolled 1649 age
      matched men and women with intermediate pretest probability of coronary artery
      disease (CAD) undergoing stress echocardiography for suspicion of CAD. Patients
      with known CAD were excluded. Those who consented to participate in the study
      were randomised to undergo either CSE or RTMCE. Events were defined as death, non
      fatal myocardial infarction (MI) and need for revascularisation. RESULTS: Median
      follow-up was 2.6 years (927 women, 722 men). Mean age was 58+/-13 years in both
      sexes. There were a total of 62 deaths, 12 MIs and 85 revascularisations with a 2
      year event rate of 3.5% (95% CI 2.7% to 4.7%). Male sex was a significant
      independent predictor of adverse outcome (death, non-fatal MI) in both CSE and
      RTMCE (CSE HR 2.07, 95% CI 1.07 to 4.02, RTMCE HR 2.14; 95% CI 1.04 to 4.33).
      Higher 2-year event rates were noted in men in comparison with women after a
      normal CSE (men 5.4%, women 1.6%, p=0.02), but not after a normal RTMCE (men
      5.8%, women 3.7%, p=0.41). Event rates were also significantly higher in men
      after an abnormal RTMCE (men 34.8%, women 16.4%, p=0.02) but no difference in
      outcome between sexes was observed after an abnormal CSE (men 17.8%, women 18.6%,
      p=0.90). CONCLUSIONS: The addition of perfusion imaging with RTMCE improves the
      predictive value of stress echocardiography in men with no known CAD, but does
      not improve the predictive value in age-matched women.

PMID- 25608748
TI  - Coronary disease in pregnancy.

PMID- 25608749
TI  - Mode of delivery for pregnant women with heart disease.

PMID- 25608750
TI  - Angiopoietin-1 enhances skeletal muscle regeneration in mice.
AB  - Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis
      is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang
      1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle
      satellite cell survival; however, its role in skeletal muscle regeneration after
      injury is unknown. We assessed the effects of Ang-1 on fiber regeneration,
      myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA)
      in mice. We also assessed endogenous Ang-1 levels and localization in intact and
      injured TA muscles. TA fiber injury was triggered by cardiotoxin injection.
      Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin
      then increased during the 2 wk. Ang-1 protein was expressed in satellite cells,
      both in noninjured and recovering TA muscles. Positive Ang-1 staining was present
      in blood vessels but not in nerve fibers. Four days after the initiation of
      injury, injection of adenoviral Ang-1 into injured muscles resulted in
      significant increases in in situ TA muscle contractility, muscle fiber
      regeneration, and capillary density. In cultured human skeletal myoblasts,
      recombinant Ang-1 protein increased survival, proliferation, migration, and
      differentiation into myotubes. The latter effect was associated with significant
      upregulation of the expression of the myogenic regulatory factors MyoD and
      Myogenin and certain genes involved in cell cycle regulation. We conclude that
      Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury
      and that this effect is mediated through induction of the myogenesis program in
      muscle progenitor cells and the angiogenesis program in endothelial cells.

PMID- 25608752
TI  - Plasticity of renal endocrine function.
AB  - The kidneys are important endocrine organs. They secrete humoral factors, such as
      calcitriol, erythropoietin, klotho, and renin into the circulation, and
      therefore, they are essentially involved in the regulation of a variety of
      processes ranging from bone formation to erythropoiesis. The endocrine functions
      are established by cells, such as proximal or distal tubular cells, renocortical
      interstitial cells, or mural cells of afferent arterioles. These endocrine cells
      are either fixed in number, such as tubular cells, which individually and
      gradually upregulate or downregulate hormone production, or they belong to a pool
      of cells, which display a recruitment behavior, such as erythropoietin- and renin
      producing cells. In the latter case, regulation of humoral function occurs via
      (de)recruitment of active endocrine cells. As a consequence renin- and
      erythropoietin-producing cells in the kidney show a high degree of plasticity by
      reversibly switching between distinct cell states. In this review, we will focus
      on the characteristics of renin- and of erythropoietin-producing cells,
      especially on their origin and localization, their reversible transformations,
      and the mediators, which are responsible for transformation. Finally, we will
      discuss a possible interconversion of renin and erythropoietin expression.

PMID- 25608753
TI  - A collaborative strategy to tackle tuberculosis in England.

PMID- 25608751
TI  - Female rats selectively bred for high intrinsic aerobic fitness are protected
      from ovariectomy-associated metabolic dysfunction.
AB  - Ovariectomized rodents model human menopause in that they rapidly gain weight,
      reduce spontaneous physical activity (SPA), and develop metabolic dysfunction,
      including insulin resistance. How contrasting aerobic fitness levels impacts
      ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats
      selectively bred for high and low intrinsic aerobic fitness [high-capacity
      runners (HCR) and low-capacity runners (LCR), respectively] were maintained under
      sedentary conditions for 39 wk. Midway through the observation period, OVX or
      sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR
      OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before
      and 4 wk after surgery, while body composition via dual-energy X-ray
      absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and
      skeletal muscle phenotype, hepatic lipid content, insulin resistance via
      homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids
      were assessed at death. Remarkably, HCR were protected from OVX-associated
      increases in adiposity and insulin resistance, observed only in LCR. HCR rats
      were ~30% smaller, had ~70% greater spontaneous physical activity (SPA), consumed
      ~10% more relative energy, had greater skeletal muscle proliferator-activated
      receptor coactivator 1-alpha, and ~40% more BAT. OVX did not increase energy
      intake and reduced SPA to the same extent in both HCR and LCR. LCR were
      particularly affected by an OVX-associated reduction in resting energy
      expenditure and experienced a reduction in relative BAT; resting energy
      expenditure correlated positively with BAT across all animals (r = 0.6; P <
      0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic
      fitness protects against OVX-associated increases in adiposity and insulin
      resistance. The mechanism may involve preservation of resting energy expenditure.

PMID- 25608754
TI  - Blood as medicine: social meanings of blood and the success of Ebola trials.

PMID- 25608755
TI  - Corticosteroids and pneumonia: time to change practice.

PMID- 25608757
TI  - Vaginal epithelium and microflora characteristics in women with premature ovarian
      failure under hormone therapy compared to healthy women.
AB  - PURPOSE: To evaluate some microbiological aspects of the vaginal flora and the
      vaginal trophism of women with premature ovarian failure (POF) in use of oral
      hormone therapy. METHODS: A cross-sectional study with 36 women with POF under
      the age of 40 years using oral hormonal therapy. They were age matched with 36
      women with normal gonadal function (control group). The characteristics of the
      vaginal epithelium were assessed through the hormonal vaginal cytology, vaginal
      pH measurement and vaginal health index to identify vaginal disturbances. Vaginal
      microflora was evaluated by the amine test, bacterioscopy (Nugent score) and
      culture for fungi to identify vaginal abnormal microflora and fungi infections.
      RESULTS: Despite the fact that there were no statistical significant differences
      related to the cytological aspects and pH measurements, it was found that the
      vaginal health index was highly superior in the control group than in the POF
      group (23.4 +/- 1.8 vs 20.8 +/- 3.5), p < 0.0001 despite both groups had trophic
      scores. There were no statistical significance differences regarding to vaginal
      microflora types and fungi infection. CONCLUSION: Oral hormone therapy for young
      women with POF seems to be good enough to reestablish the epithelium cells,
      vaginal pH and microflora.

PMID- 25608756
TI  - Adjunct prednisone therapy for patients with community-acquired pneumonia: a
      multicentre, double-blind, randomised, placebo-controlled trial.
AB  - BACKGROUND: Clinical trials yielded conflicting data about the benefit of adding
      systemic corticosteroids for treatment of community-acquired pneumonia. We
      assessed whether short-term corticosteroid treatment reduces time to clinical
      stability in patients admitted to hospital for community-acquired pneumonia.
      METHODS: In this double-blind, multicentre, randomised, placebo-controlled trial,
      we recruited patients aged 18 years or older with community-acquired pneumonia
      from seven tertiary care hospitals in Switzerland within 24 h of presentation.
      Patients were randomly assigned (1:1 ratio) to receive either prednisone 50 mg
      daily for 7 days or placebo. The computer-generated randomisation was done with
      variable block sizes of four to six and stratified by study centre. The primary
      endpoint was time to clinical stability defined as time (days) until stable vital
      signs for at least 24 h, and analysed by intention to treat. This trial is
      registered with ClinicalTrials.gov, number NCT00973154. FINDINGS: From Dec 1,
      2009, to May 21, 2014, of 2911 patients assessed for eligibility, 785 patients
      were randomly assigned to either the prednisone group (n=392) or the placebo
      group (n=393). Median time to clinical stability was shorter in the prednisone
      group (3.0 days, IQR 2.5-3.4) than in the placebo group (4.4 days, 4.0-5.0;
      hazard ratio [HR] 1.33, 95% CI 1.15-1.50, p<0.0001). Pneumonia-associated
      complications until day 30 did not differ between groups (11 [3%] in the
      prednisone group and 22 [6%] in the placebo group; odds ratio [OR] 0.49 [95% CI
      0.23-1.02]; p=0.056). The prednisone group had a higher incidence of in-hospital
      hyperglycaemia needing insulin treatment (76 [19%] vs 43 [11%]; OR 1.96, 95% CI
      1.31-2.93, p=0.0010). Other adverse events compatible with corticosteroid use
      were rare and similar in both groups. INTERPRETATION: Prednisone treatment for 7
      days in patients with community-acquired pneumonia admitted to hospital shortens
      time to clinical stability without an increase in complications. This finding is
      relevant from a patient perspective and an important determinant of hospital
      costs and efficiency. FUNDING: Swiss National Science Foundation, Viollier AG,
      Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner
      Stiftung.

PMID- 25608758
TI  - The evaluation of reliability and contribution of frozen section pathology to
      staging endometrioid adenocarcinomas.
AB  - PURPOSE: To evaluate the reliability and accuracy of intraoperative pathological
      findings, compared to permanent section (PS) and to understand contributions of
      frozen section (FS) to final staging in patients with endometrioid carcinomas.
      METHODS: This is a retrospective analysis of 79 patients undergoing
      intraoperative FS and with endometrioid adenocarcinomas. Intraoperative
      pathological findings were compared with final results as to grade, depth of
      myometrial invasion (MI), cervical involvement, lymphovascular space invasion
      (LVSI) and stage. We also analyzed whether staging procedures like pelvic or para
      aortic lymph node metastasis, peritoneal cytology and extension beyond of uterus
      were related to FS findings. Staging was based on the FIGO 2009. RESULTS: FS
      results were agreement in 89.9 % for grade, 88.6 % for depth of MI, 100 % for
      cervical invasion, and 92.4 % for LVSI, compared with PS. On FS, 12, 16.6 and
      44.4 % of specimens in stages of IA, IB and II became upstaged in final
      pathology, respectively. Of 79 cases, 5 (6.3 %) were upstaged to IIIC1, and 3
      (3.8 %) were upstaged to IIIC2 because of lymph node metastasis. A significant
      relationship was detected between lymph node metastasis, and FS grades (p =
      0.001), LVSI (p = 0.000), cervical invasion (p = 0.006) and MI (p = 0.001).
      CONCLUSION: We consider that intraoperative FS is a useful procedure to identify
      poor prognostic pathological factors. While grading, depth of MI, cervical
      stromal invasion and LVSI on FS are significant in predicting lymph node
      metastasis, the existence of cervical stromal invasion and LVSI should be
      considered more effective parameters in the identification of metastatic
      endometrial cancer risks.

PMID- 25608759
TI  - Hiding in the dark: uncovering cancer drivers through image-guided genomics.
AB  - Genome analysis which takes into account tumor purity leads to discovery of PTEN
      as a tumor suppressor gene in high-grade serous ovarian cancer. 

PMID- 25608761
TI  - The impact of 18 F-FET PET-CT on target definition in image-guided stereotactic
      radiotherapy in patients with skull base lesions.
AB  - BACKGROUND: 18 F-fluoro-ethyl-tyrosine PET is gaining more indications in the
      field of oncology. We investigated the potentials of usage of FET-PET/CT in
      addition to MRI for definition of gross tumor volume (GTV) in stereotactic
      radiotherapy of lesions of skull base. METHODS: We included in a prospective
      setting 21 cases. An MRI was performed, completed by FET PET/CT. Different GTV's
      were defined based on respective imaging tools: 1. GTVMRI, 2. GTV MRI /CT, 3. GTV
      composit (1 + 2), and GTVPET = GTV Boost. Lesions could be visualised by MRI and
      FET-PET/CT in all patients. RESULTS: FET tracer enhancement was found in all
      cases. Skull base infiltration by these lesions was observed by MRI, CT (PET/CT)
      and FET-PET (PET/CT) in all patients. Totally, brain tissue infiltration was seen
      in 10 patients. While, in 7 (out 10) cases, MRI and CT (from PET/CT) were
      indicating brain infiltration, FET-PET could add additional information regarding
      infiltrative behaviour: in 3 (out 10) patients, infiltration of the brain was
      displayed merely in FET-PET. An enlargement of GTVMRI/CT due to the FET-PET
      driven information, which revealed GTVcomposite , was necessary in 7 cases,. This
      enlargement was significant by definition (> 10% of GTVMRI/CT). The mean PET
      effect on GTV counted for 1 +/- 4 cm3. The restricted boost fields were based
      mainly on the GTVPET volume. In mean, about 8.5 cm3 of GTVMRI/CT, which showed no
      FET uptake, were excluded from target volume. GTV boost driven by only-PET
      activity, was in mean by 33% smaller than the initial large treatment field, GTV
      composite, for those cases received boost treatment. FET-PET lead to significant
      (>10%) changes in the initial treatment fields in 11/21 patients and showed
      additional tumour volume relevant for radiation planning in 6/21 cases, and led
      to a subsequent decrease of more than 10% of the initial volumes for the boost
      fields. CONCLUSION: The implementation of FET PET into the planning procedures
      showed a benefit in terms of accurate definition of skull base lesions as targets
      for Image-guided stereotactic Radiotherapy. This has to be investigated
      prospectively in larger cohorts.

PMID- 25608760
TI  - Comparison of two methods to report potentially avoidable hospitalizations in
      France in 2012: a cross-sectional study.
AB  - BACKGROUND: Potentially avoidable hospitalizations represent an indirect measure
      of access to effective primary care. However many approaches have been proposed
      to measure them and results may differ considerably. This work aimed at examining
      the agreement between the Weissman and Ansari approaches in order to measure
      potentially avoidable hospitalizations in France. METHODS: Based on the 2012
      French national hospital discharge database (Programme de Medicalisation des
      Systemes d'Information), potentially avoidable hospitalizations were measured
      using two approaches proposed by Weissman et al. and by Ansari et al. Age- and
      sex-standardised rates were calculated in each department. The two approaches
      were compared for diagnosis groups, type of stay, severity, age, sex, and length
      of stay. RESULTS: The number and age-standardised rate of potentially avoidable
      hospitalizations estimated by the Weissman et al. and Ansari et al. approaches
      were 742,474 (13.3 cases per 1,000 inhabitants) and 510,206 (9.0 cases per 1,000
      inhabitants), respectively. There are significant differences by conditions
      groups, age, length of stay, severity level, and proportion of medical stays
      between the Weissman and Ansari methods. CONCLUSIONS: Regarding potentially
      avoidable hospitalizations in France in 2012, the agreement between the Weissman
      and Ansari approaches is poor. The method used to measure potentially avoidable
      hospitalizations is critical, and might influence the assessment of accessibility
      and performance of primary care.

PMID- 25608762
TI  - Anti-inflammatory T-cell shift in neuropathic pain.
AB  - BACKGROUND: The classification of pain into nociceptive and neuropathic pain is
      based on characteristic symptoms and different pathophysiological mechanisms. In
      a recent investigation, we found a disrupted TH17/Treg balance in patients
      suffering from chronic unspecific low back pain (CLBP). These patients did not
      show any signs of neuropathy. There is evidence for a considerable impact of the
      immune system also in neuropathic pain. However, the role of the adaptive immune
      system is still unclear. In the present study, we investigated systemic T-cell
      subset responses and T-cell related cytokine profiles in patients with chronic
      neuropathic pain. METHODS: We analyzed T-cell subsets, mRNA expression and T-cell
      related cytokine profiles in 26 patients suffering from neuropathic pain in
      comparison to 26 healthy controls. Using multicolor flow cytometry (FACS), we
      quantified the number of T helper cells 1 (TH1), TH2, TH17 and regulatory T-cells
      (Tregs). Forkhead-Box-Protein 3 (FoxP3), Transforming growth factor-beta (TGF
      beta) and RAR-related orphan receptor-gammaT (ROR-gammaT) mRNA expression was
      determined by quantitative real-time PCR (qPCR) and levels of pain-related
      cytokines were measured by Human Cytokine Multiplex Immunoassay (Macrophage
      inflammatory protein-1alpha (MIP-1alpha), Tumor necrosis factor-alpha (TNF
      alpha), Interferon-gamma (IFN-gamma), Interleukin (IL) -4, IL-6, IL-10, IL-17,
      and IL-23). RESULTS: We found a TH17/Treg imbalance with significantly increased
      anti-inflammatory Tregs and decreased pro-inflammatory TH17 cells in patients
      with neuropathic pain as compared to healthy controls. These results were
      confirmed on mRNA level: Treg-related FoxP3 and TGF-beta mRNA expression was
      elevated, whereas expression of TH17-related RORgammaT was reduced. Cytokine
      analyses revealed only marginal changes. CONCLUSIONS: Our investigation revealed
      a clear shift of T-cell subsets towards anti-inflammation in patients with
      neuropathic pain. Interestingly, this is quite similar to our previous findings
      in CLBP patients, but even more pronounced. Therefore, it remains to be
      elucidated in future investigations whether the immune changes represent an
      underlying pathophysiological mechanism or an epiphenomenon induced by ongoing
      pain and stress. GERMAN CLINICAL TRIAL REGISTER (DRKS): Trial registration
      number: DRKS00005954.

PMID- 25608763
TI  - Recently discovered Aedes japonicus japonicus (Diptera: Culicidae) populations in
      The Netherlands and northern Germany resulted from a new introduction event and
      from a split from an existing population.
AB  - BACKGROUND: Originally native to East Asia, Aedes japonicus japonicus, a
      potential vector of several arboviruses, has become one of the most invasive
      mosquito species in the world. After having established in the USA, it is now
      spreading in Europe, with new populations emerging. In contrast to the USA, the
      introduction pathways and modes of dispersal in Europe are largely obscure.
      METHODS: To find out if two recently detected populations of Ae. j. japonicus in
      The Netherlands and northern Germany go back to new importations or to movements
      within Europe, the genetic makeup of mosquito specimens from all known European
      populations was compared. For this purpose, seven microsatellite loci from a
      representative number of mosquito specimens were genotyped and part of their
      mitochondrial nad4 gene sequenced. RESULTS: A novel nad4 haplotype found in the
      newly discovered Dutch population of Ae. j. japonicus suggests that this
      population is not closely related to the other European populations but has
      emanated from a further introduction event. With five nad4 haplotypes, the Dutch
      population also shows a very high genetic diversity indicating that either the
      founder population was very large or multiple introductions took place. By
      contrast, the recently detected North German population could be clearly assigned
      to one of the two previously determined European Ae. j. japonicus microsatellite
      genotypes and shows nad4 haplotypes that are known from West Germany. CONCLUSION:
      As the European populations of Ae. j. japonicus are geographically separated but
      genetically mixed, their establishment must be attributed to passive
      transportation. In addition to intercontinental shipment, it can be assumed that
      human activities are also responsible for medium- and short-distance overland
      spread. A better understanding of the processes underlying the introduction and
      spread of this invasive species will help to increase public awareness of the
      human-mediated displacement of mosquitoes and to find strategies to avoid it.

PMID- 25608764
TI  - Bone-marrow-derived very small embryonic-like stem cells in patients with
      critical leg ischaemia: evidence of vasculogenic potential.
AB  - Very small embryonic-like stem cells (VSELs) are multipotent stem cells localised
      in adult bone marrow (BM) that may be mobilised into peripheral blood (PB) in
      response to tissue injury. We aimed to quantify VSELs in BM and PB of patients
      with critical limb ischaemia (CLI) and to test their angiogenic potential in
      vitro as well as their therapeutic capacity in mouse model of CLI. We isolated BM
      VSELs from patients with CLI and studied their potential to differentiate into
      vascular lineages. Flow and imaging cytometry showed that VSEL counts were lower
      in BM (p< 0.001) and higher (p< 0.001) in PB from CLI patients compared to
      healthy controls, suggesting that ischaemia may trigger VSELs mobilisation in
      this patient population. Sorted BM-VSELs cultured in angiogenic media acquired a
      mesenchymal phenotype (CD90+, Thy-1 gene positive expression). VSEL-derived cells
      had a pattern of secretion similar to that of endothelial progenitor cells, as
      they released low levels of VEGF-A and inflammatory cytokines. Noteworthy, VSELs
      triggered post-ischaemic revascularisation in immunodeficient mice (p< 0.05 vs
      PBS treatment), and acquired an endothelial phenotype either in vitro when
      cultured in the presence of VEGF-B (Cdh-5 gene positive expression), or in vivo
      in Matrigel implants (human CD31+ staining in neo-vessels from plug sections). In
      conclusion, VSELs are a potential new source of therapeutic cells that may give
      rise to cells of the endothelial lineage in humans.

PMID- 25608765
TI  - Dimensions of Learning Organizations Questionnaire (DLOQ) in a low-resource
      health care setting in Nepal.
AB  - BACKGROUND: Knowledge-based organizations, such as health care systems, need to
      be adaptive to change and able to facilitate uptake of new evidence. To be able
      to assess organizational capability to learn is therefore an important part of
      health systems strengthening. The aim of the present study is to assess context
      using the Dimensions of the Learning Organization Questionnaire (DLOQ) in a low
      resource health setting in Nepal. METHODS: DLOQ was translated and administered
      to 230 employees at all levels of the hospital. Data was analyzed using non
      parametric tests. RESULTS: The DLOQ was able to detect variations across
      employee's perceptions of the organizational context. Nurses scored significantly
      lower than doctors on the dimension "Empowerment" while doctors scored lower than
      nurses on "Strategic leadership". These results suggest that the hospital's
      organization carries attributes of a centralized, hierarchical structure that
      might hinder a progress towards a learning organization. CONCLUSIONS: This study
      demonstrates that, despite the designing and developing of the DLOQ in the USA
      and its main utilization in company settings, it can be used and applied in
      hospital settings in low-income countries. The application of DLOQ provides
      valuable insights and understanding when designing and evaluating efforts for
      healthcare improvement.

PMID- 25608767
TI  - Breast Imaging Second Opinions Impact Surgical Management.
AB  - BACKGROUND: Breast surgeons often see women for second opinions for abnormalities
      found on breast imaging. For second opinions, these images are submitted for
      review and interpretation by dedicated breast imagers. This study evaluated the
      conformity of results among interpretation of imaging submitted from outside
      hospitals both from tertiary care centers, as well as community programs, in an
      attempt to evaluate the utility of this practice for the sake of clinical
      management and resource utilization. METHODS: A retrospective chart review was
      conducted on all breast patients that submitted outside imaging films for the
      years 2011 to 2013 at Rush University Medical Center (RUMC). The radiologic
      diagnosis and each patient's proposed management plan was collected and evaluated
      for concordance between the outside institutions and RUMC. RESULTS: A total of
      380 patients who presented for second opinions with an interpretation of outside
      exams were evaluated. In 47.4 % [95 % confidence interval (CI) 42.4-52.4] of
      cases there was distinct variance in radiologic impression. For 53.5 % (95 % CI
      48.4-58.5) of patients, there was a change in recommended management plan, which
      included recommendations for either additional imaging or need for additional
      biopsy. In total, this changed the overall surgical management in 27.1 % (95 % CI
      22.8-31.9) of cases. In six patients, the reinterpretation of outside imaging
      detected new malignancies not previously identified. Overall, 83.7 % (95 % CI
      79.7-87.1) of patients who submitted imaging from outside institutions chose to
      complete the remainder of their treatment at RUMC. CONCLUSIONS: The practice of
      second opinion review changed overall definitive management at our specialty
      center in more than one in four cases. In addition, the review identified six
      previously unrecognized malignancies. Given this data, the practice of second
      opinions and interpretation of outside exams should continue despite the
      additional resources required.

PMID- 25608768
TI  - Laparoscopic Suprapancreatic Lymph Node Dissection for Advanced Gastric Cancer
      Using a Left-Sided Approach.
AB  - BACKGROUND: We developed a novel procedure for laparoscopic suprapancreatic lymph
      node (LN) dissection, which is compulsory and quite difficult for patients with
      advanced gastric cancer.1 (-) 3 METHODS: We dissected suprapancreatic LNs from
      the left to the right side. The No. 11p LNs were dissected first, followed by the
      No. 9, 7, and 8a LNs. Dissection of the No. 5 and 12a LNs was completed last. The
      above procedure was performed on 814 consecutive patients with stage cT2-3
      disease. RESULTS: Mean operation time was 186.9 +/- 56.4 min (range 80-480 min),
      mean blood loss was 76.6 +/- 106.8 ml (range 3-500 ml), and mean times to first
      flatus, fluid diet, and soft diet were 3.7 +/- 1.2 days (range 1-9 days), 5.2 +/-
      1.7 days (range 2-14 days), and 8.3 +/- 2.2 days (range 5-20 days), respectively.
      A mean 34.5 +/- 12.9 LNs (range 22-103) were retrieved, including a mean 12.4 +/-
      5.7 (range 0-35) suprapancreatic area LNs. Overall postoperative morbidity rate
      was 14.7 % (120/814), including three cases of pancreatic fistula. All of these
      postoperative complications were successfully treated by conservative methods. At
      a median follow-up of 27 months (range 1-63), cumulative 3-year overall survival
      was 59.2 %. CONCLUSION: Laparoscopic suprapancreatic LN dissection using a left
      sided approach could be safely achieved and is more convenient for advanced
      gastric cancer.

PMID- 25608769
TI  - Role of surgery in patients with recurrent, metastatic, or unresectable locally
      advanced gastrointestinal stromal tumors sensitive to imatinib: a retrospective
      analysis of the Spanish Group for Research on Sarcoma (GEIS).
AB  - BACKGROUND: Recurrent, metastatic, and locally advanced gastrointestinal stromal
      tumors (GISTs) can be treated successfully with imatinib mesylate. Surgery for
      residual disease has been suggested for nonrefractory metastatic GISTs to reduce
      the probability of resistant recurrent clones, although no randomized Phase III
      trial has been performed to answer the question about its benefit. We carried out
      an analysis of the outcome of patients with recurrent unresectable locally
      advanced or metastatic imatinib-sensitive priamary GIST in 14 institutions in
      Spain. We compared two cohorts: treated or not treated with surgery after partial
      response or stabilization by imatinib. PATIENTS AND METHODS: Data were obtained
      from the online GIST registry of the Spanish Group for Research in Sarcomas.
      Selected patients were then divided into two groups: group A, treated initially
      only with imatinib, and group B, treated additionally with metastasectomy.
      Baseline characteristics between groups were compared, and univariate and
      multivariate analysis for progression-free survival and overall survival (OS)
      were performed. RESULTS: Analysis was undertaken in 171 patients considered
      nonrefractory to imatinib. The median follow-up time was 56.6 months. Focusing on
      OS, the Eastern Cooperative Oncology Group performance status different than 0,
      extent of disease limited to one metastatic organ, and comparison between groups
      A or B achieved statistical difference in the multivariate analysis. Median
      survival was 59.9 months in group A and 87.6 months in group B. CONCLUSIONS:
      Based in its benefit in OS, our study supports surgery of metastatic disease in
      GIST patients who respond to imatinib therapy.

PMID- 25608770
TI  - Evaluation of malignancy risk stratification of microcalcifications detected on
      mammography: a study based on the 5th edition of BI-RADS.
AB  - BACKGROUND: The 5th edition of Breast Imaging Reporting and Data System
      subdivides suspicious calcifications into two categories: 4B-amorphous, coarse
      heterogeneous, and fine pleomorphic calcifications; 4C-fine linear or fine linear
      branching calcifications. We investigated whether these revised categories are
      appropriate for malignancy risk stratification. METHODS: We studied 246 patients
      (mean age 48.2 years) with suspicious microcalcifications detected on mammography
      who underwent stereotactic biopsy (n = 154) or surgical excisional biopsy with
      preoperative mammogram-guided needle localization (n = 92). Pre-biopsy mammograms
      were reviewed retrospectively, and imaging features were analyzed according to
      the revised morphology and distribution descriptors. Pathological results of
      stereotactic biopsy and surgical excision were considered, with the surgical
      results being the reference standard. Positive predictive values (PPVs) were
      calculated and compared using the chi (2) test or Fisher's exact test. RESULTS:
      Overall PPV of suspicious microcalcifications was 22.4 %. PPVs of morphology
      descriptors were as follows: amorphous 7.9 %, coarse heterogeneous 17.8 %, fine
      pleomorphic 63.2 %, fine linear/fine linear branching 100 % (p < 0.001). PPVs of
      distribution descriptors were as follows: regional 8.8 %, grouped 14.3 %, linear
      87.5 %, segmental 63.6 % (p < 0.001). For morphology and distribution descriptors
      combinations, PPVs for amorphous/regional and amorphous/grouped
      microcalcifications were 4.2 and 7.6 %, resepectively. The PPV for fine
      pleomorphic/linear or segmental was 93.8 %. CONCLUSIONS: Subcategorization of
      morphology descriptors for suspicious microcalcifications is needed because of
      the different PPVs for amorphous, coarse heterogeneous, and fine pleomorphic
      microcalcifications. Combining morphology and distribution descriptors for
      suspicious microcalcifications provides accurate risk stratification.

PMID- 25608771
TI  - Retropharyngeal lymph node metastasis in 54 patients with oropharyngeal squamous
      cell carcinoma who underwent surgery-based treatment.
AB  - BACKGROUND: This study aimed to determine the incidence, risk factors, and
      prognostic significance of retropharyngeal lymph node (RPLN) metastasis from
      malignancies of the oropharynx. METHODS: The study retrospectively analyzed 54
      patients with oropharyngeal squamous cell carcinoma who underwent primary surgery
      based treatment. Most of the patients had advanced stage (stage 3 or 4, 96.3 %)
      oropharyngeal cancer. Surgery alone was performed for 14 patients. Postoperative
      radiotherapy was administered to 14 patients and chemoradiation to 26 patients.
      Genotyping and detection of human papillomavirus (HPV) was available for 52
      patients. RESULTS: Using pathologic analysis, RPLN metastasis was confirmed in 22
      subjects. The patients with RPLN metastasis had a significantly lower disease
      specific survival rate than the non-RPLN metastasis group (54.5 vs 75 %; p =
      0.05). The pN+ (RPLN) yield of these cases was 18/22 (81.8 %) for cN+ (RPLN)
      versus 4/32 (7.4 %) for cN0 (RPLN). Multivariate analysis identified the
      independent factors associated with RPLN metastasis as radiographically positive
      retropharyngeal node (p = 0.012; odds ratio [OR] 53.920) and posterior pharyngeal
      wall invasion (p = 0.021; OR 33.014). A high-risk HPV-positive result was not
      significantly correlated with RPLN metastasis. CONCLUSIONS: Elective RPLN
      dissection should be considered for patients with advanced neck and primary
      tumor, particularly those with posterior pharyngeal wall invasion.

PMID- 25608773
TI  - Erratum to: Intratumor Textural Heterogeneity on Pretreatment 18F-FDG PET Images
      Predicts Response and Survival After Chemoradiotherapy for Hypopharyngeal Cancer.

PMID- 25608772
TI  - Tumoral CD10 expression correlates with aggressive histology and prognosis in
      patients with malignant pleural mesothelioma.
AB  - BACKGROUND: Currently, tumor-node-metastasis stage and histologic type are the
      established prognostic factors for malignant pleural mesothelioma, whereas no
      prognostic markers have been established for clinical practice. We investigated
      the prognostic value of CD10, a metalloproteinase that can promote cancer
      aggressiveness through enzymatic degradation and intracellular signaling
      crosstalk, in malignant pleural mesothelioma. METHODS: CD10 immunostaining was
      performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148;
      biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative
      (no staining) or positive (any staining). Epithelioid tumors were classified as
      pleomorphic subtype when cytologic pleomorphism was >=10 % of the tumor. Overall
      survival (OS) was analyzed by log-rank tests and Cox proportional hazard models.
      RESULTS: Tumoral CD10 expression was identified in 42 % of epithelioid non
      pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic
      tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was
      correlated with higher mitotic count (p = 0.002). Overall survival for patients
      with positive CD10 expression was significantly shorter than that for patients
      with negative CD10 expression in all patients (p = 0.001) and in patients with
      epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an
      independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019).
      CONCLUSIONS: Tumoral CD10 expression correlated with aggressive histologic types
      and higher mitotic activity and is an independent prognostic factor for patients
      with malignant pleural mesothelioma.

PMID- 25608775
TI  - Organisational culture and post-merger integration in an academic health centre:
      a mixed-methods study.
AB  - BACKGROUND: Around the world, the last two decades have been characterised by an
      increase in the numbers of mergers between healthcare providers, including some
      of the most prestigious university hospitals and academic health centres.
      However, many mergers fail to bring the anticipated benefits, and successful post
      merger integration in university hospitals and academic health centres is even
      harder to achieve. An increasing body of literature suggests that organisational
      culture affects the success of post-merger integration and academic-clinical
      collaboration. METHODS: This paper reports findings from a mixed-methods single
      site study to examine 1) the perceptions of organisational culture in academic
      and clinical enterprises at one National Health Service (NHS) trust, and 2) the
      major cultural issues for its post-merger integration with another NHS trust and
      strategic partnership with a university. From the entire population of 72
      clinician-scientists at one of the legacy NHS trusts, 38 (53%) completed a
      quantitative Competing Values Framework survey and 24 (33%) also provided
      qualitative responses. The survey was followed up by semi-structured interviews
      with six clinician-scientists and a group discussion including five senior
      managers. RESULTS: The cultures of two legacy NHS trusts differed and were
      primarily distinct from the culture of the academic enterprise. Major cultural
      issues were related to the relative size, influence, and history of the legacy
      NHS trusts, and the implications of these for respective identities, clinical
      services, and finances. Strategic partnership with a university served as an
      important ameliorating consideration in reaching trust merger. However, some
      aspects of university entrepreneurial culture are difficult to reconcile with the
      NHS service delivery model and may create tension. CONCLUSIONS: There are
      challenges in preserving a more desirable culture at one of the legacy NHS
      trusts, enhancing cultures in both legacy NHS trusts during their post-merger
      integration, and in aligning academic and clinical cultures following strategic
      partnership with a university. The seeds of success may be found in current best
      practice, good will, and a near identical ideal of the future preferred culture.
      Strong, fair leadership will be required both nationally and locally for the
      success of mergers and post-merger integration in university hospitals and
      academic health centres.

PMID- 25608776
TI  - Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing
      liver fibrosis.
AB  - BACKGROUND: Limited data are available regarding the role of magnetic resonance
      imaging (MRI), particularly the new generation 3 Tesla technology, and especially
      diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our
      pilot study was to assess the clinical performance of the apparent diffusion
      coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in
      patients with non-alcoholic fatty liver disease (NAFLD). METHODS: 18 patients
      with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with
      single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm2. ADC was
      measured in four locations in the liver and the mean ADC value was used for
      analysis. Staging of fibrosis was performed according to the METAVIR system.
      RESULTS: The median age of patients was 52 years (range 23-73). The distribution
      of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5),
      4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm2
      (r= -0.30, P=0.27). However it was significantly associated with ADC at b value
      of 0-1000 s/mm2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm2) the area
      under receiver-operating characteristic curve was 0.93 for fibrosis stage >=3 and
      the optimal ADC cut-off value was 1.16 *10-3 mm2/s. CONCLUSION: 3 Tesla DWI can
      possibly predict the presence of advanced fibrosis in patients with NAFLD.

PMID- 25608777
TI  - Circadian rhythms in rheumatology--a glucocorticoid perspective.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in
      regulating and controlling immune responses. Dysfunction of the HPA axis has been
      implicated in the pathogenesis of rheumatoid arthritis (RA) and other rheumatic
      diseases. The impact of glucocorticoid (GC) therapy on HPA axis function also
      remains a matter of concern, particularly for longer treatment duration.
      Knowledge of circadian rhythms and the influence of GC in rheumatology is
      important: on the one hand we aim for optimal treatment of the daily undulating
      inflammatory symptoms, for example morning stiffness and swelling; on the other,
      we wish to disturb the HPA axis as little as possible. This review describes
      circadian rhythms in RA and other chronic inflammatory diseases, dysfunction of
      the HPA axis in RA and other rheumatic diseases and the recent concept of the
      hepato-hypothalamic-pituitary-adrenal-renal axis, the problem of adrenal
      suppression by GC therapy and how it can be avoided, and evidence that
      chronotherapy with modified release prednisone effective at 02:00 a.m. can
      inhibit proinflammatory sequelae of nocturnal inflammation better compared with
      GC administration in the morning but does not increase the risk of HPA axis
      insufficiency in RA. 

PMID- 25608778
TI  - Assessing fungal community structure from mineral surfaces in Kartchner Caverns
      using multiplexed 454 pyrosequencing.
AB  - Research on the distribution and structure of fungal communities in caves is
      lacking. Kartchner Caverns is a wet and mineralogically diverse carbonate cave
      located in an escarpment of Mississippian Escabrosa limestone in the Whetstone
      Mountains, Arizona, USA. Fungal diversity from speleothem and rock wall surfaces
      was examined with 454 FLX Titanium sequencing technology using the Internal
      Transcribed Spacer 1 as a fungal barcode marker. Fungal diversity was estimated
      and compared between speleothem and rock wall surfaces, and its variation with
      distance from the natural entrance of the cave was quantified. Effects of
      environmental factors and nutrient concentrations in speleothem drip water at
      different sample sites on fungal diversity were also examined. Sequencing
      revealed 2,219 fungal operational taxonomic units (OTUs) at the 95% similarity
      level. Speleothems supported a higher fungal richness and diversity than rock
      walls. However, community membership and the taxonomic distribution of fungal
      OTUs at the class level did not differ significantly between speleothems and rock
      walls. Both OTU richness and diversity decreased significantly with increasing
      distance from the natural cave entrance. Community membership and taxonomic
      distribution of fungal OTUs also differed significantly between the sampling
      sites closest to the entrance and those furthest away. There was no significant
      effect of temperature, CO2 concentration, or drip water nutrient concentration on
      fungal community structure on either speleothems or rock walls. Together, these
      results suggest that proximity to the natural entrance is a critical factor in
      determining fungal community structure on mineral surfaces in Kartchner Caverns.

PMID- 25608780
TI  - [Current situation and prospect of measures of rehabilitation after burn injury].
AB  - In the wound healing process after a deep burn injury, improper treatment in the
      early stage and lack of functional rehabilitation measures in the late stage
      usually lead to hyperplastic scar, joint contracture, synarthrophysis, and other
      deformities. All of them may result in cosmetic and functional impairments, loss
      of work ability, poor life quality, and even psychopathy of the patients. Thus,
      the improvement in rehabilitation methods and the maximal recovery of appearance
      and functions have drawn intense attention. This article mainly discusses the
      prevention, systematic treatment principles and methods for the hyperplastic scar
      and scar contracture, as well as the problems need to be solved in burn
      rehabilitation, based on the introduction of the new advancement in the
      rehabilitation techniques. 

PMID- 25608781
TI  - [Effects of early treatment with ultrashort wave combined with sequential
      pressure on functional recovery of deeply burned hands].
AB  - OBJECTIVE: To study the effects of ultrashort wave combined with sequential
      pressure treatment on the functional recovery of deeply burned hands in the early
      stage of healed wounds in hands. METHODS: Sixty-five patients with burn of
      unilateral hand were hospitalized from July 2012 to June 2013 in our center.
      Injured hands of 35 patients were treated with active movement, ultrashort wave,
      sequential pressure therapy, and pressure gloves, and the other 30 patients were
      treated with active movement and pressure gloves 10-31 days after the wounds were
      healed according to the will of patients. The former 35 patients were regarded as
      comprehensive treatment (CT) group, and the latter 30 patients were regarded as
      routine treatment (RT) group. Before treatment and 4 weeks after treatment, the
      appearance of injured hands was observed; the circumference of the proximal
      segment of thumb, index, and middle fingers and that of the palmar crease and
      wrist crease were measured to evaluate swelling of injured hand; score and grade
      of function of injured hands were evaluated with a Carroll Upper Extremity
      Functional Test. Data were processed with t test and rank sum test. RESULTS: (1)
      Four weeks after treatment, appearance of 30 injured hands in group CT was
      improved, which was close to that of the normal hand of each patient, while
      contracture deformity of metacarpophalangeal joints and interphalangeal joints
      was observed in the other 5 injured hands. Four weeks after treatment, no obvious
      change in the appearance of 17 injured hands in group RT was observed compared
      with that before treatment, while hyperextension of metacarpophalangeal joints,
      flexion of interphalangeal joints, and adduction deformity of thumb were observed
      in the other 13 hands. (2) Four weeks after treatment, the circumferential values
      of the proximal segment of thumb, index, and middle fingers and the palmar crease
      and wrist crease of injured hands in group CT were respectively lower than those
      before treatment (with t values 3.26-4.24, P values below 0.01), and the
      circumferential values of the proximal segment of thumb and middle fingers and
      the wrist crease of injured hands in group RT were respectively lower than those
      before treatment (with t values 2.02-2.44, P values below 0.05). The difference
      values of circumference values of the proximal segment of thumb, index, and
      middle fingers and the palmar crease and wrist crease of injured hands between
      before treatment and 4 weeks after treatment were respectively (0.491 +/- 0.022),
      (0.583 +/- 0.089), (0.486 +/- 0.021), (1.100 +/- 0.076), (0.751 +/- 0.053) cm in
      group CT, which were significantly higher than those in group RT [(0.306 +/-
      0.021), (0.277 +/- 0.022), (0.320 +/- 0.027), (0.700 +/- 0.052), (0.483 +/-
      0.048) cm, with t values respectively 5.94, 3.11, 5.02, 4.22, 3.68, P values
      below 0.01]. (3) Four weeks after treatment, scores of function of injured hands
      in groups CT and RT were respectively higher than those before treatment (with t
      values respectively 14.40 and 4.00, P values below 0.001), and the grades of
      function of injured hands were respectively improved (with u values respectively
      6.93 and 3.29, P values below 0.01). The difference value of scores of function
      of injured hands between before treatment and 4 weeks after treatment was (51.1
      +/- 2.2) points in group CT, which was significantly higher than that of group RT
      [(32.5 +/- 4.8) points, t = 3.52, P < 0.001]. CONCLUSIONS: Ultrashort wave
      combined with sequential pressure and routine rehabilitation treatment of deeply
      burned hands in the early stage after wounds in hands are healed can obviously
      reduce the swelling of injured hands, which provides a favorable condition for
      active movements and systematic rehabilitation treatment later.

PMID- 25608782
TI  - [Curative effects of kinesitherapy in combination with self-made simple orthosis
      in treatment of scar contracture of burned hand in children].
AB  - OBJECTIVE: To survey the curative effects of kinesitherapy in combination with
      self-made simple orthosis (SO) in treatment of scar contracture of burned hand in
      children. METHODS: Fifty-eight children with burns of unilateral hand and
      received treatment in our rehabilitation center from January 2012 to January 2014
      were divided into common rehabilitation (CR) and SO groups according to the
      random number table, with 29 cases in each group. After the wounds were healed,
      patients in group CR were treated with kinesitherapy combined with hand game
      exercises and pressure gloves, while patients in group SO were treated with
      kinesitherapy combined with hand game exercises and self-made SO, which was
      composed of finger web dividing belt, self-adhesive bandage, and infusion set
      fixing plate. Before treatment and 16 weeks after treatment, scar condition was
      assessed with the Vancouver Scar Scale (VSS); hand function was evaluated by the
      Jebsen Test of Hand Function, and the completion time was recorded; and the
      activities of daily life (ADL) was measured by the modified Barthel Index.
      Sixteen weeks after treatment, the range of motion was measured with the Total
      Active Movement (TAM) method. Data were processed with t test and chi-square
      test. RESULTS: The score of VSS in group SO was (12.2 +/- 1.3) points before
      treatment and (6.7 +/- 2.2) points 16 weeks after treatment, and the improvement
      score was (5.6 +/- 1.8) points. The score of VSS in group CR was (12.0 +/- 1.4)
      points before treatment and (7.0 +/- 1.8) points 16 weeks after treatment, and
      the improvement score was (5.0 +/- 1.0) points. There was no obvious difference
      in improvement score of VSS between the two groups (t = 1.452, P = 0.152). The
      ratio of excellent and good results according to TAM method in group SO was 75.9%
      (22/29) , while it was 37.9% (11/29) in group CR (t = 8.507, P = 0.004). The
      completion time for the Jebsen Test of group OS was (8.2 +/- 1.6) min before
      treatment and (7.1 +/- 1.4) min after treatment, and the improvement time was
      (1.2 +/- 1.5) min. The completion time for the Jebsen Test of group CR was (9.0
      +/- 1.9) min before treatment and (6.3 +/- 1.4) min 16 weeks after treatment, and
      the improvement time was (2.7 +/- 2.7) min. There was a significant difference in
      improvement time for the Jebsen Test between the two groups (t = 2.618, P =
      0.012). The score of ADL in group CR was (7.7 +/- 1.4) points before treatment
      and (10.4 +/- 1.4) points 16 weeks after treatment, and the improvement score was
      (2.7 +/- 1.7) points. The score of ADL in group CR was (7.8 +/- 1.4) points
      before treatment and (9.5 +/- 1.4) points 16 weeks after treatment, and the
      improvement score was (1.7 +/- 1.6) points. There was a significant difference in
      improvement score of ADL between the two groups (t = 2.246, P = 0.029).
      CONCLUSIONS: Kinesitherapy in combination with self-made SO can improve the
      functional recovery of burned hand in children and prevent contractures in hand,
      and it is worth applying generally.

PMID- 25608783
TI  - [Analysis on polymorphism at -509 C/T site of TGF-beta1 gene in patients with
      keloids].
AB  - OBJECTIVE: To analyze the polymorphism at -509C/T site of TGF-beta1 gene in
      patients with keloids, and to explore its relationship with the occurrence of
      keloid and its influence on the plasma level of TGF-beta1. METHODS: One hundred
      and sixty-nine patients with keloids and hospitalized from June 2011 to April
      2014 were included as keloid group, and 119 healthy blood donors were enrolled as
      healthy control group. Venous blood of study subjects was collected. The -509C/T
      genotype of TGF-beta1 gene was determined with PCR-restriction fragment length
      polymorphism technique combined with DNA sequence analysis, and the frequency of
      allele C or T was calculated. The theoretical frequency of the 3 genotypes CC,
      CT, and TT was calculated according to the theory of Hardy-Weinberg equilibrium
      to determine whether the gene frequency of the study subject was group
      representative or not. The distribution of -509C/T genotype of TGF-beta1 gene
      among patients in keloid group was analyzed by grouping in gender, age, with or
      without family history of keloid, and the number of keloid respectively. Plasma
      level of TGF-beta1 of all study subjects was determined with ELISA, and the
      plasma level TGF-beta1 of patients with various -509C/T genotypes of TGF-beta1
      gene in keloid group was analyzed. The relative risk of allele frequency of
      patients in keloid group was analyzed by Logistic regression analysis, and the
      other data were processed with chi-square test and t test. RESULTS: Among the 
      509C/T genotypes of TGF-beta1 gene between subjects in the two groups, the
      distribution of genotypes CC, CT, and TT was quite similar, and they were
      respectively 38 cases (22.5%), 79 cases (46.7%), and 52 cases (30.8%) in keloid
      group and 39 persons (32.8%), 52 persons (43.7%), and 28 persons (23.5%) in
      healthy control group (chi2 = 4.225, P>0.05). The distribution frequency of
      alleles C and T in the two groups were obviously different, and they were
      respectively 45.9% and 54.1% in keloid group and 54.6% and 45.4% in healthy
      control group (chi2 = 4.291, P<0.05). The theoretical frequency values of the
      three kinds of genotypes of CC, CT, and TT were respectively 35 cases (21.0%), 84
      cases (49.7%), and 50 cases (29.3%) in keloid group, and 35 persons (29.8%), 59
      persons (49.6%), and 25 persons (20.6%) in healthy control group. There were no
      statistically significant differences between the actual genotype frequency and
      the theoretical values (with chi2 values respectively 0.581 and 1.672, P values
      above 0.05), showing that the research group reached Hardy-Weinberg equilibrium.
      Relative risk analysis of allele frequency showed that the risk of suffering from
      keloid of patients carrying allele C was 1.421 times of that of patients without
      carrying allele C (odds ratio = 1.421, with 95% confidence interval 1.109-1.983,
      P < 0.05). The distribution of -509C/T genotypes of TGF-beta1 gene among patients
      in keloid group was similar by grouping in gender, age, and number of keloid
      (with chi2 values 0.895-5.008, P values above 0.05). Between patients with or
      without family history of keloid, the differences of distribution frequencies of
      genotypes CC and CT were significantly different, which were respectively 61.8%
      (21/34) and 37.8% (51/135) in patients with family history of keloid and 14.7%
      (5/34) and 34.1% (46/135) in patients without a family history of keloid, with
      chi2 values respectively 6.391 and 4.835, P values below 0.05; the distribution
      frequency of genotype TT was close (chi2 = 0.292, P > 0.05). The plasma level of
      TGF-beta1 of patients in keloid group was (42 +/- 9) ug/L, which was
      significantly higher than that of people in healthy control group ?[(34 +/- 8)
      ug/L, t = 4.408, P < 0.05?]. In keloid group, the plasma level of TGF-beta1 in
      patients with genotype CC and that of patients with genotype CT was quite
      similar, which were respectively (43 +/- 9) and (40 +/- 9) ug/L (t = 0.680, P >
      0.05), and they were significantly higher than that of patients with genotype TT
      ?[(34 +/- 8) ug/L, with t values respectively 2.676 and 2.137, P values below
      0.05?]. CONCLUSIONS: TGF-beta1 gene -509C/T polymorphism was shown to be present
      in patients with keloids who were admitted to our hospital. It was shown to
      influence the plasma level of TGF-beta1 in patients. The individuals who carry
      TGF-beta1 allele C may increase the risk of developing keloid by promoting the
      expression of TGF-beta1.

PMID- 25608784
TI  - [Effects of group psychological counseling on self-confidence and social
      adaptation of burn patients].
AB  - OBJECTIVE: To explore the effects of group psychological counseling on the self
      confidence and social adaptation of burn patients during the course of
      rehabilitation. METHODS: Sixty-four burn patients conforming to the inclusion
      criteria and hospitalized from January 2012 to January 2014 in Xijing Hospital
      were divided into trial group and control group according to the method of
      rehabilitation, with 32 cases in each group. Patients in the two groups were
      given ordinary rehabilitation training for 8 weeks, and the patients in trial
      group were given a course of group psychological counseling in addition. The
      Rosenberg's Self-Esteem Scale was used to evaluate the changes in self-confidence
      levels, and the number of patients with inferiority complex, normal feeling, self
      confidence, and over self-confidence were counted before and after treatment. The
      Abbreviated Burn-Specific Health Scale was used to evaluate physical function,
      psychological function, social relationship, health condition, and general
      condition before and after treatment to evaluate the social adaptation of
      patients. Data were processed with t test, chi-square test, Mann-Whitney U test,
      and Wilcoxon test. RESULTS: (1) After treatment, the self-confidence levels of
      patients in trial group were significantly higher than those in control group (Z
      = -2.573, P < 0.05). Among trial group, the number of patients with inferiority
      complex was 17 (53.1%) before treatment, which was decreased to 6 (18.8%) after
      treatment; the number of patients with normal feeling and that of self-confidence
      were 8 (25.0%) and 4 (12.5%) before treatment, which were respectively increased
      to 13 (40.6%) and 10 (31.3%) after treatment. The overall difference in trial
      group was obvious between before and after treatment (Z = -4.123, P < 0.01) .
      There was no obvious difference in self-confidence level of patients in control
      group between before and after treatment (Z = -1.000, P > 0.05). (2) After
      treatment, the scores of psychological function, social relationship, health
      condition, and general condition were (87 +/- 3), (47.8 +/- 3.6), (49 +/- 3), and
      (239 +/- 10) points in trial group, which were significantly higher than those in
      control group [(79 +/- 4), (38.3 +/- 5.6), (46 +/- 4), and (231 +/- 9) points,
      with t values respectively -8.635, -8.125, -3.352, -3.609, P values below 0.01].
      After treatment, the scores of physical function, psychological function, social
      relationship, health condition, and general condition in trial group were
      significantly higher than those before treatment (with t values from -33.282 to 
      19.515, P values below 0.05). The scores of physical function, psychological
      function, health condition, and general condition in control group after
      treatment were significantly higher than those before treatment (with t values
      from -27.137 to -17.790, P values below 0.05). CONCLUSIONS: Group psychological
      counseling combined with ordinary rehabilitation training give rise to
      significant effects on self-confidence level and social adaptation for burn
      patients.

PMID- 25608785
TI  - [Analysis of diagnosis and management of 21 patients with Marjolin's ulcers].
AB  - OBJECTIVE: To investigate the clinical manifestation, diagnosis, and treatment of
      patients with Marjolin's ulcers. METHODS: The clinical materials of 21 patients
      with Marjolin's ulcers hospitalized from January 2007 to January 2013 were
      retrospectively analyzed, including age, gender, injury causes, duration time of
      primary disease in developing Marjolin's ulcer, duration of ulcer, lesion site,
      ulcer area, symptoms and signs of ulcer region, bacterial culture results before
      operation, histopathological type, grade of carcinoma cell differentiation, depth
      of invasion, treatment, and outcome. RESULTS: (1) The age of 21 patients at the
      time of diagnosis of Marjolin's ulcers was 19-74 (47 +/- 13) years, and the ratio
      of male to female was nearly 0.9:1.0. (2) The main primary lesions were flame
      burns and high temperature liquid scald, respectively occurred in 12 cases
      (57.1%) and 7 cases (33.3%). The time for development of Marjolin's ulcers from
      primary injury was 10-56 (40 +/- 14) years. (3) Ulceration on top of scar lasted
      for longer than one year in 12 patients (57.1%). (4) Lesion site was mainly
      located in the limbs in 13 patients (61.9%), and on head and face in 6 patients
      (28.6%), respectively. (5) Ulcer area ranged 0.25-74.25 (39 +/- 25) cm(2). Foul
      excretion, bleeding, intensified pain, and gradual enlargement of ulceration were
      observed in the lesion of most patients. (6) Bacterial culture of wound excretion
      before operation showed positive results in 16 patients (76.2%). RESULTS: of
      bacterial culture of blood were negative in all patients. (7) Pathological
      examination revealed squamous cell carcinoma in 20 cases and basal cell carcinoma
      in 1 case, and mostly of high or medium differentiation. Cancer cells in nearly
      40% patients had invaded the subcutaneous tissue or deeper area. (8) All patients
      were treated by surgery, among them autologous skin grafting was done after
      excision of lesion in 11 patients, and in 5 patients the defects were closed with
      skin flaps after excision of lesion, and in 5 patients limbs harboring the lesion
      were amputated. Twelve patients (57.1%) received postoperative rehabilitation
      treatment. Two patients with pulmonary metastasis received chemotherapy. (9) Most
      of the flaps and skin grafts survived well after surgery, and a few cases with
      failure of skin grafting or transplantation of flaps underwent skin grafts again.
      Patients were followed up for 6 months to 5 years, in 4 patients recurrence
      occurred after surgery, and 2 of them died. The other patients survived without
      recurrence. CONCLUSIONS: Squamous cell carcinoma was the most common pathological
      type of Marjolin's ulcer admitted to our unit. A recurrent ulcer with long course
      should be considered as Marjolin's ulcer, and it should be scrutinized
      pathologically. Currently, surgery remains the optimal treatment for Marjolin's
      ulcer. Regular follow-up should be carried out after resection of the lesion to
      detect carcinoma recurrence and metastasis.

PMID- 25608786
TI  - [Advances in the research of Marjolin's ulcer].
AB  - Marjolin's ulcer is a rare malignancy arising from various forms of scars, mainly
      an old scar resulted from burn. The second most common origin is malignant
      degeneration arising from tissue within osteomyelitis fistulae. Not uncommonly,
      the lesions may arise secondary to ulcers due to venous insufficiency or pressure
      sores. The pathology of the majority of Marjolin's ulcer is a well-differentiated
      squamous cell carcinoma. The exact reason for an ulcer which undergoes a
      malignant transformation is unknown. The pathologic diagnosis is the gold
      standard. Surgery remains the preferred treatment after diagnosis is reached.
      Wide surgical excision with margins up to 2-3 cm has been suggested. The
      necessity of whether lymphatic dissection should be executed, or radiotherapy and
      chemotherapy following surgery is still in dispute. This article deals with the
      etiology of Marjolin's ulcer and its pathological grading, diagnosis, treatment,
      prognosis, and prevention, with a hope to provide some useful clinical
      information. 

PMID- 25608787
TI  - [Scarless fetal wound healing and its mechanism].
AB  - Scarless healing is considered as the most ideal mode of wound repair. This
      ability generally exists in the early period of mammalian embryos, however it
      gradually turns to scar healing with the development of the embryos. This
      phenomenon is the result of the interaction of multiple biological functions, and
      the mechanism is still uncertain. This article deals with a systematical review
      of literature concerning the mechanism of scarless healing based on the recent
      experimental studies, hoping to provide evidence for the treatment of wounds to
      realize scarless healing in adult. 

PMID- 25608779
TI  - Repeat instability during DNA repair: Insights from model systems.
AB  - The expansion of repeated sequences is the cause of over 30 inherited genetic
      diseases, including Huntington disease, myotonic dystrophy (types 1 and 2),
      fragile X syndrome, many spinocerebellar ataxias, and some cases of amyotrophic
      lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat expansions are
      dynamic, and disease inheritance and progression are influenced by the size and
      the rate of expansion. Thus, an understanding of the various cellular mechanisms
      that cooperate to control or promote repeat expansions is of interest to human
      health. In addition, the study of repeat expansion and contraction mechanisms has
      provided insight into how repair pathways operate in the context of structure
      forming DNA, as well as insights into non-canonical roles for repair proteins.
      Here we review the mechanisms of repeat instability, with a special emphasis on
      the knowledge gained from the various model systems that have been developed to
      study this topic. We cover the repair pathways and proteins that operate to
      maintain genome stability, or in some cases cause instability, and the cross-talk
      and interactions between them. 

PMID- 25608788
TI  - [Effects of hydrogen-rich saline on liver of severely scalded rats with delayed
      resuscitation].
AB  - OBJECTIVE: To explore the effects of hydrogen-rich saline (HS) on liver of
      severely scalded rats with delayed resuscitation. METHODS: Twenty-four SD rats
      were inflicted with 40% TBSA full-thickness scald using a temperature-controlled
      scalding apparatus. The injured rats were divided into lactated Ringer's solution
      (RS) and HS groups according to the random number table, with 12 rats in each
      group. Rats in groups RS and HS were respectively resuscitated with an
      intraperitoneal injection of 4 mL * kg-1 * %TBSA-1 of RS or HS (self-prepared,
      with concentration of hydrogen 0.6 mmol/L) 6 hours after injury up to 48 hours
      after scald. The infusion volume of the second 24 hours after injury was a half
      of that of the first 24 hours. At post scald hour (PSH) 6 (before resuscitation),
      12, 24, and 48, blood was collected from the heart of 3 rats in each group, and
      then the rats were sacrificed for harvesting liver tissue. The pathological
      change in liver tissue was observed with HE staining. The number of hepatic
      neutrophils was counted with a hematocytometer. Serum levels of AST and ALT were
      determined with full-automatic biochemical analyzer. Contents of TNF-alpha, IL
      1beta, IL-6, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver tissue were
      determined with ELISA. Absorbance value of malondialdehyde (MDA) in liver tissue
      was detected and quantified with spectrophotometer. Data were processed with
      analysis of variance of repeated measurement and LSD-t test. RESULTS: At PSH 48,
      moderate infiltration of inflammatory cells and hepatic hyperemia were observed
      in rats of group HS as compared with group RS. At PSH 12, 24, and 48, the number
      of neutrophils in group HS was respectively (25.3 +/- 1.8) * 105, (19.6 +/- 0.6)
      * 105, and (14.1 +/- 3.2) * 105 cells per mililitre, and they were significantly
      lower than those in group RS ?[(31.9 +/- 2.0) * 105, (30.9 +/- 2.2) * 105, and
      (23.8 +/- 3.0) * 105 cells per mililitre, with t values respectively 5.6, 7.6,
      and 8.7, P values below 0.05?]. At PSH 6 and 12, the serum levels of AST and ALT
      and the levels of TNF-alpha, IL-1beta, and IL-6 in liver tissue were close
      between the two groups (with t values respectively 0.3-3.9 and 0.9-3.8, P values
      above 0.05). At PSH 24 and 48, the serum levels of AST and ALT in group HS were
      respectively (308 +/- 24) and (210 +/- 15) U/L and (93 +/- 7) and (70 +/- 5) U/L,
      which were significantly lower than those in group RS ?[(541 +/- 39) and (505 +/-
      18) U/L, with t values respectively 17.5 and 16.7, P values below 0.05; (156 +/-
      9) and (166 +/- 21) U/L, with t values respectively 30.3 and 6.9, P values below
      0.05?]. At PSH 24 and 48, the levels of TNF-alpha, IL-1beta, and IL-6 in liver
      tissue in group HS were respectively (20.7 +/- 1.6) and (13.7 +/- 1.5) pg/mg,
      (7.7 +/- 1.5) and (6.3 +/- 1.2) pg/mg, and (8.7 +/- 1.2) and (6.0 +/- 2.0) pg/mg,
      which were significantly lower than those in group RS ?[(32.7 +/- 5.0) and (25.7
      +/- 4.0) pg/mg, with t values respectively 5.2 and 5.7, P values below 0.05;
      (16.3 +/- 2.5) and (12.0 +/- 2.7) pg/mg, with t values both as 4.7, P values
      below 0.05; (14.7 +/- 2.1) and (13.3 +/- 1.5) pg/mg, with t values respectively
      10.4 and 4.4, P values below 0.05?]. The level of MDA at PSH 6 and levels of 8
      OHdG at PSH 6 and 12 in liver tissue were close between the two groups (with t
      values respectively 0.1, 0.7, and 4.3, P values above 0.05). In group HS, the
      levels of MDA in liver tissue at PSH 12, 24, and 48 were respectively (15.3 +/-
      1.5), (8.7 +/- 1.2), and (6.7 +/- 1.5) mmol/mg, and the levels of hepatic 8-OHdG
      at PSH 24 and 48 were respectively (124 +/- 12) and (79 +/- 10) pg/mg, which were
      significantly lower than those in group RS ?[(27.3 +/- 4.7), (20.3 +/- 1.5), and
      (14.0 +/- 1.0) mmol/mg, with t values respectively 5.2, 5.7, and 5.1, P values
      below 0.05; (191 +/- 10) and (136 +/- 15) pg/mg, with t values respectively 8.0
      and 8.1, P values below 0.05?]. CONCLUSIONS: Resuscitation with HS could protect
      liver of severely scalded rats with delayed resuscitation possibly by reducing
      infiltration of neutrophils, thus lowering the content of inflammatory cytokines,
      and effectively alleviating oxidative stress.

PMID- 25608789
TI  - [Effects of rat allogeneic adipose-derived stem cells on the early
      neovascularization of autologous fat transplantation].
AB  - OBJECTIVE: To investigate the effects of allogeneic adipose-derived stem cells
      (ADSCs) of rat on the early neovascularization of autologous fat transplantation.
      METHODS: (1) Experiment 1. Adipose tissue was collected from both inguinal
      regions of two SD rats to isolate, culture, and purify ADSCs through collagen
      enzyme digestion, density gradient centrifugation, and adherence method. The
      fourth passage of cells were collected for morphologic observation, detection of
      expressions of surface markers CD34, CD49d, CD106, and CD45 of ADSCs with flow
      cytometer, identification of adipogenic and osteogenic differentiation, and
      determination of the cell proliferation ability with thiazolyl blue method. (2)
      Experiment 2. Another 30 SD rats were divided into allogeneic adipose granule
      (AG) group (A, n = 6), autologous AG group (B, n = 8), autologous
      ADSCs+autologous AG group (C, n = 8), and allogeneic ADSCs+autologous AG group
      (D, n = 8) according to the random number table. The fourth passage of ADSCs were
      obtained from adipose tissue from one side of inguinal region of SD rats in group
      C. Adipose tissue obtained from one side of inguinal region of SD rats of the
      other 3 groups was abandoned. The AG was prepared from another side of inguinal
      region of SD rats in the 4 groups. The mixture of 0.6 g AG from one rat and 1 mL
      DMEM/F12 nutrient solution was injected subcutaneously into the back of another
      rat in group A, and so on. Autologous AG was injected into its own body of the
      rats in group B. The mixture of 1 mL autologous ADSCs mixture which contains 3.0
      * 106 cells per mililitre autologous ADSCs combined with autologous AG was
      injected into the rats in group C. The mixture of 1 mL allogeneic ADSCs mixture
      which contains 3.0 * 106 cells per mililitre ADSCs extractived from the former 2
      rats in experiment 1 combined with autologous AG was injected into the rats in
      group D. At 7 days post transplantation, fat transplants were harvested for gross
      observation, measurement of wet weight, pathological observation, and assessment
      of cells with positive expression of CD31 with immunohistochemical method. Data
      were processed with one-way analysis of variance and SNK test. RESULTS: (1) The
      fourth passage of cells proliferated well showing fusiform shape similar to
      fibroblasts. These cells showed positive expression of CD34 and CD49d and weak
      positive expression of CD106 and CD45. They were able to differentiate into
      adipocytes and osteoblasts. These cells were identified as ADSCs. The fourth
      passage of cells grew faster than that of the tenth passage. (2) At 7 days post
      transplantation, no liquifying necrosis or infection was observed in the fat
      transplants of the rats in the 4 groups. Wet weight of the fat transplants in
      groups A and B was respectively (0.25 +/- 0.04) and (0.26 +/- 0.03) g, which were
      less than those of groups C and D [(0.36 +/- 0.03) and (0.35 +/- 0.04) g, with P
      values below 0.05]. HE staining showed that there were less fat cells and more
      fibroblasts in the transplants of group A, visible fibrous tissue around uneven
      shape of fat cells in the transplants of group B, and almost identical size and
      shape of fat cells and unobvious fibrous tissues were found in the transplants of
      groups C and D. The cells with positive expression of CD31 were distributed in
      fibrous tissues in larger number but less around fat cells in the transplants of
      group A, while more of these cells were observed surrounding fat cells in the
      transplants of group B. There were more cells with positive expression of CD31
      distributed surrounding fat cells in the transplants of groups C and D than that
      in group B. The cells with positive expression of CD31 observed under 400 times
      field were more in number in groups C (20.5 +/- 1.1) and D (22.1 +/- 1.0) than in
      groups A (8.0 +/- 3.6) and B (10.9 +/- 1.7), with P values below 0.05.
      CONCLUSIONS: Allogeneic ADSCs combined with autologous AG can significantly
      improve the early vascularization of fat transplantation as well as autologous
      ADSCs combined with autologous AG.

PMID- 25608790
TI  - [Advances in the research of treating refractory diabetic wounds with stem
      cells].
AB  - With the growth of aging society, China has become the country of population with
      the highest incidence of diabetes in the world. Diabetes leads to pathological
      changes in vascular and nervous system, rendering the diabetic skin fragile and
      hard to heal if wounded; in the end most diabetic wounds tend to become chronic
      skin ulcers. The refractory diabetic wound is the result of various endogenous
      and exogenous factors. It is a quite complicated pathophysiologic event which
      lacks an effective and specific therapeutic method in clinic. The use of stem
      cells could be a new approach of treating diabetic chronic wounds since they have
      a potential ability of self-renovation and multi-directional differentiation
      which will promote angiogenesis and wound healing process, thus be beneficial in
      the care of ischemia diseases of the lower limb. This article reviews basic
      theory of treating diabetic wound and the changes in microenvironment, and
      prompts many successful cases in curing refractory diabetic wounds. 

PMID- 25608791
TI  - Mutual information reveals multiple structural relaxation mechanisms in a model
      glass former.
AB  - Among the key challenges to our understanding of solidification in the glass
      transition is that it is accompanied by little apparent change in structure.
      Recently, geometric motifs have been identified in glassy liquids, but a causal
      link between these motifs and solidification remains elusive. One 'smoking gun'
      for such a link would be identical scaling of structural and dynamic lengthscales
      on approaching the glass transition, but this is highly controversial. Here we
      introduce an information theoretic approach to determine correlations in
      displacement for particle relaxation encoded in the initial configuration of a
      glass-forming liquid. We uncover two populations of particles, one inclined to
      relax quickly, the other slowly. Each population is correlated with local density
      and geometric motifs. Our analysis further reveals a dynamic lengthscale similar
      to that associated with structural properties, which may resolve the discrepancy
      between structural and dynamic lengthscales. 

PMID- 25608792
TI  - Determining the pathogenicity of genetic variants associated with cardiac
      channelopathies.
AB  - Advancements in genetic screening have generated massive amounts of data on
      genetic variation; however, a lack of clear pathogenic stratification has left
      most variants classified as being of unknown significance. This is a critical
      limitation for translating genetic data into clinical practice. Genetic screening
      is currently recommended in the guidelines for diagnosis and treatment of cardiac
      channelopathies, which are major contributors to sudden cardiac death in young
      people. We propose to characterize the pathogenicity of genetic variants
      associated with cardiac channelopathies using a stratified scoring system. The
      development of this system was considered by using all of the tools currently
      available to define pathogenicity. The use of this scoring system could help
      clinicians to understand the limitations of genetic associations with a disease,
      and help them better define the role that genetics can have in their clinical
      routine. 

PMID- 25608793
TI  - Broadening the future of value account of the wrongness of killing.
AB  - On Don Marquis's future of value account of the wrongness of killing, 'what makes
      it wrong to kill those individuals we all believe it is wrong to kill, is that
      killing them deprives them of their future of value'. Marquis has recently argued
      for a narrow interpretation of his future of value account of the wrongness of
      killing and against the broad interpretation that I had put forward in response
      to Carson Strong. In this article I argue that the narrow view is problematic
      because it violates some basic principles of equality and because it allows for
      some of the very killing that Marquis sets out to condemn; further, I argue that
      the chief reason why Marquis chooses the narrow view over the broad view-namely
      that the broad view would take the killing of some non-human animals to be also
      wrong-should rather be considered a welcome upshot of the broad view. 

PMID- 25608794
TI  - Prolonged, reversible neurologic symptoms after carpet sea anemone envenomation
      in a pet store worker.

PMID- 25608797
TI  - Structure-odor correlations in homologous series of alkanethiols and attempts to
      predict odor thresholds by 3D-QSAR studies.
AB  - Homologous series of alkane-1-thiols, alkane-2-thiols, alkane-3-thiols, 2
      methylalkane-1-thiols, 2-methylalkane-3-thiols, 2-methylalkane-2-thiols, and
      alkane-1,omega-dithiols were synthesized to study the influence of structural
      changes on odor qualities and odor thresholds. In particular, the odor thresholds
      were strongly influenced by steric effects: In all homologous series a minimum
      was observed for thiols with five to seven carbon atoms, whereas increasing the
      chain length led to an exponential increase in the odor threshold. Tertiary
      alkanethiols revealed clearly lower odor thresholds than found for primary or
      secondary thiols, whereas neither a second mercapto group in the molecule nor an
      additional methyl substitution lowered the threshold. To investigate the impact
      of the SH group, odor thresholds and odor qualities of thiols were compared to
      those of the corresponding alcohols and (methylthio)alkanes. Replacement of the
      SH group by an OH group as well as S-methylation of the thiols significantly
      increased the odor thresholds. By using comparative molecular field analysis, a
      3D quantitative structure-activity relationship model was created, which was able
      to simulate the odor thresholds of alkanethiols in good agreement with the
      experimental results. NMR and mass spectrometric data for 46 sulfur-containing
      compounds are additionally supplied.

PMID- 25608796
TI  - Construction and characterization of VL-VH tail-parallel genetically engineered
      antibodies against staphylococcal enterotoxins.
AB  - Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus have
      increasingly given rise to human health and food safety. Genetically engineered
      small molecular antibody is a useful tool in immuno-detection and treatment for
      clinical illness caused by SEs. In this study, we constructed the V(L)-V(H) tail
      parallel genetically engineered antibody against SEs by using the repertoire of
      rearranged germ-line immunoglobulin variable region genes. Total RNA were
      extracted from six hybridoma cell lines that stably express anti-SEs antibodies.
      The variable region genes of light chain (V(L)) and heavy chain (V(H)) were
      cloned by reverse transcription PCR, and their classical murine antibody
      structure and functional V(D)J gene rearrangement were analyzed. To construct the
      eukaryotic V(H)-V(L) tail-parallel co-expression vectors based on the "5'-V(H)
      ivs-IRES-V(L)-3'" mode, the ivs-IRES fragment and V(L) genes were spliced by two
      step overlap extension PCR, and then, the recombined gene fragment and V(H) genes
      were inserted into the pcDNA3.1(+) expression vector sequentially. And then the
      constructed eukaryotic expression clones termed as p2C2HILO and p5C12HILO were
      transfected into baby hamster kidney 21 cell line, respectively. Two clonal cell
      lines stably expressing V(L)-V(H) tail-parallel antibodies against SEs were
      obtained, and the antibodies that expressed intracytoplasma were evaluated by
      enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry.
      SEs can stimulate the expression of some chemokines and chemokine receptors in
      porcine IPEC-J2 cells; mRNA transcription level of four chemokines and chemokine
      receptors can be blocked by the recombinant SE antibody prepared in this study.
      Our results showed that it is possible to get functional V(L)-V(H) tail-parallel
      genetically engineered antibodies in same vector using eukaryotic expression
      system.

PMID- 25608798
TI  - Tribute to William L. Jorgensen.

PMID- 25608795
TI  - FOXP3+ Tregs: heterogeneous phenotypes and conflicting impacts on survival
      outcomes in patients with colorectal cancer.
AB  - The tumor microenvironment composites a mixture of immune lymphoid cells, myeloid
      cells, stromal cells with complex cytokines, as well as numerous lymphovascular
      vessels. Colorectal cancer (CRC) is a common malignancy and one of the leading
      causes of tumor-related death in the United States and worldwide. The immune
      status in the tumor microenvironment contributes to the survival of a patient
      with CRC. Regulatory T cells (Tregs) are considered a key factor in immune escape
      and immunotherapy failure among cancer patients. The transcription factor
      forkhead box P3 (FOXP3) is a crucial intracellular marker and also a key
      developmental and functional factor for CD4+CD25+ Tregs. Tregs are correlated
      with survival in various human neoplasms, and elevated proportions of Tregs are
      usually associated with unfavorable clinical outcomes. However, the role of Tregs
      in CRC remains controversial. High densities of tumor-infiltrating Tregs in CRC
      patients are reported to be correlated with worse or better outcomes. And Tregs
      may not be predictive of prognosis after resection of the primary tumor. The
      exact explanations for these discordant results remain unclear. The heterogeneous
      instincts of cell phenotype, gene expression, and functional activities of Tregs
      may partly contribute this contrasting result. Furthermore, the lack of a robust
      marker for identifying Tregs or due to the different techniques applied is also
      account. The Treg-specific demethylated region (TSDR) was recently reported to be
      a specific epigenetic marker for natural Tregs (nTregs), which can stably express
      FOXP3. The FOXP3-TSDR demethylation assay may be an promising technique for CRC
      related nTregs studies. 

PMID- 25608799
TI  - Autobiography of William L. Jorgensen: scientific history and recollections.

PMID- 25608802
TI  - Which oral hypoglycaemic for gestational diabetes?

PMID- 25608803
TI  - Interferon-based combination treatment for chronic hepatitis C in the era of
      direct acting antivirals.
AB  - The development of protease inhibitors (PIs) such as telaprevir and boceprevir
      constitutes a milestone in chronic hepatitis C antiviral treatment since it has
      achieved sustained virological response (SVR) rates of up to 75% in naive and 29
      88% in treatment-experienced patients with genotype 1 infection. Both require
      combination treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) as
      PI monotherapy results in resistant mutations. New direct acting antiviral agents
      (DAAs) have recently been approved or their approval is imminent. Simeprevir
      administered orally as one pill per day in combination with PEG-IFN/RBV will be
      the next PI to be approved. The SVR rates at about 72-80% for treatment-naive
      patients are not a major improvement over telaprevir or boceprevir. However, this
      treble combination has fewer side effects and drug-drug interactions and most
      patients undergo shorter treatment duration (24 months) due to earlier treatment
      responses. Sofosbuvir is the first available once-daily NS5B polymerase inhibitor
      which has been approved in combination with PEG-IFN/RBV for just 12 weeks with
      89% SVR in treatment-naive patients with genotype 1 infection and 83-100% in
      treatment-experienced patients with genotypes 2/3. The current review focuses on
      the recent rapid and continuous developments in the management of chronic HCV
      infection with DAAs in combination with PEG-IFN/RBV.

PMID- 25608806
TI  - Occupational COPD among Danish never-smokers: a population-based study.
AB  - Occupational exposures have been shown to be risk factors for chronic obstructive
      pulmonary disease (COPD) among never-smokers. In a Danish population-based
      cohort, we analysed this association and the population attributable fraction.
      The study population (N=1575) was aged 45-84, COPD was defined by lung function
      measurements and the method of lower limit of normal (LLN), and occupational
      exposure was assessed by questionnaire and expert judgement. Furthermore, the
      estimates additionally were provided according to the Global Initiative for
      Chronic Obstructive Lung Diseases. More than a threefold increased risk (LLN
      OR=3.69 (95% CI 1.36 to 10.04) was found for occupational exposure to vapour,
      gas, dust and fumes (predominantly organic dust) in this never-smoking
      population, with a corresponding 48% (95% CI 30% to 65%) population attributable
      fraction among never-smokers. 

PMID- 25608805
TI  - Twenty years of SHIELD: decreasing incidence of occupational asthma in the West
      Midlands, UK?
AB  - INTRODUCTION: Since 2000 a decline in the incidence of occupational asthma (OA)
      has been reported in the UK and Europe. We aimed to describe and account for
      trends in the incidence of OA in the West Midlands, UK using annual notification
      data from the SHIELD voluntary surveillance scheme over the period 1991-2011.
      METHODS: All notifications to the SHIELD database between January 1991 and
      December 2011 were identified, along with patients' demographic data,
      occupations, causative agents and confirmatory tests. Annual notifications were
      scaled to give an annual count per million workers, giving a measure of
      incidence, and also standardised against those of bakers' asthma. Non-parametric
      analyses were undertaken between annual incidence and time (years) for common
      causative agents using (1) a negative binomial regression univariate model and
      (2) a logistic regression model calculating annual reporting ORs. A step-change
      analysis was used to examine time points at which there were marked reductions in
      incidence. RESULTS: A decrease in annual incidence of OA was observed over the
      study period (incident rate ratio=0.945; 95% CI 0.933 to 0.957; p<0.0001), an
      effect that was lost after standardising for bakers' asthma. Decreases in
      incidence were seen for most common causative agents, with only cleaning product
      related OA increasing over 21 years. Marked fall in incidence was seen in 2004
      for isocyanates, and in 1995 for latex. Most notifications came from a regional
      specialist occupational lung disease unit, with notifications from other sites
      falling from 16 cases/million workers/annum in 1995 to 0 in 2004. CONCLUSIONS:
      Reporter fatigue and increasing under-recognition of OA are both factors which
      contribute to the apparent fall in incidence of OA in the West Midlands. There is
      a future need for interventions that enable health professionals to identify
      potential cases of OA in the workplace and in healthcare settings.

PMID- 25608807
TI  - The roles of signaling pathways in regulating kidney development.
AB  - The development of mammalian kidney is a complex process. The reciprocal
      inductive interactions between epithelial cells and metanephric mesenchymal cells
      determine cell fates including proliferation, growth, apoptosis, and eventually
      contribute to the formation of an intact kidney. Multiple signaling pathways,
      including the GDNF/Ret, Wnt and BMP signaling pathways, have been shown to
      regulate the development of kidney. A myriad of signaling pathways and their
      cross-talks form a precise spatiotemporal regulatory network, which ensures the
      kidney to be properly organized. In this review, we summarize the physiological
      process of kidney development as well as the involved signaling pathways and
      their interplay. 

PMID- 25608804
TI  - Structure and boosting activity of a starch-degrading lytic polysaccharide
      monooxygenase.
AB  - Lytic polysaccharide monooxygenases (LPMOs) are recently discovered enzymes that
      oxidatively deconstruct polysaccharides. LPMOs are fundamental in the effective
      utilization of these substrates by bacteria and fungi; moreover, the enzymes have
      significant industrial importance. We report here the activity, spectroscopy and
      three-dimensional structure of a starch-active LPMO, a representative of the new
      CAZy AA13 family. We demonstrate that these enzymes generate aldonic acid
      terminated malto-oligosaccharides from retrograded starch and boost significantly
      the conversion of this recalcitrant substrate to maltose by beta-amylase. The
      detailed structure of the enzyme's active site yields insights into the mechanism
      of action of this important class of enzymes. 

PMID- 25608808
TI  - Functional roles of pseudogenes in cancers.
AB  - Pseudogene is a DNA fragment with high sequence similarity to the corresponding
      functional gene. Because of accumulation of multiple mutations, pseudogenes have
      lost their original functions. Previous studies indicated that pseudogenes are
      dysfunctional relatives of the corresponding functional genes, and are noises in
      the process of genome evolution. However, with the development of molecular
      biotechnologies, more and more studies have demonstrated that pseudogenes possess
      important biologic functions. For example, some pseudogene could regulate the
      expression of functional genes by competitively binding to the miRNAs, some could
      produce endogenous small interference RNAs to negatively regulate the expression
      of functional genes, and some even could encode functional proteins. In this
      review, we summarize the recent research progresses of pseudogenes through four
      aspects: the classification, identification, function, and particularly the roles
      in cancers. 

PMID- 25608809
TI  - Biological function and molecular mechanism of Twist2.
AB  - Twist2, one of the basic helix-loop-helix protein (bHLH) family members, is
      responsible for the transcriptional regulation in mesenchymal cell lineages
      during its development. Twist2 functions as a molecular switch to activate or
      repress target genes by direct or indirect mechanisms. Twist2 can directly bind
      with conserved E-box on DNA sequence, to recruit co-activators or repressors, and
      interfere with the activation or inhibition function through protein-protein
      interactions with E-protein modulators. Nonsense mutations of Twist2 cause
      Setleis syndrome. Early research on Twist2 focused on osteogenesis, and then
      expression differences were found in a wide variety of tumors. Further studies
      showed that Twist2 plays an important role in cancer epithelial-mesenchymal
      transition (EMT). Regulation function of Twist2 is controlled by temporal and
      spatial expression, phosphorylation, dimerization and cell positioning
      adjustment. The involvement of Twist2 in a broad spectrum of regulatory pathways
      highlights the importance of understanding its role in normal development,
      homeostasis and disease. In this review, we summarize the role of Twist2 in
      osteogenesis differentiation, tumor formation and EMT, and its molecular
      mechanism. It is helpful to have a thorough understanding of the biological
      functions of Twist2, and facilitate the transformation and application in
      diagnosis, development and therapy. 

PMID- 25608810
TI  - Advances on molecular mechanism of the adaptive evolution of Chiroptera (bats).
AB  - As the second biggest animal group in mammals, Chiroptera (bats) demonstrates
      many unique adaptive features in terms of flight, echolocation, auditory acuity,
      feeding habit, hibernation and immune defense, providing an excellent system for
      understanding the molecular basis of how organisms adapt to the living
      environments encountered. In this review, we summarize the researches on the
      molecular mechanism of the adaptive evolution of Chiroptera, especially the
      recent researches at the genome levels, suggesting a far more complex
      evolutionary pattern and functional diversity than previously thought. In the
      future, along with the increasing numbers of Chiroptera species genomes
      available, new evolutionary patterns and functional divergence will be revealed,
      which can promote the further understanding of this animal group and the
      molecular mechanism of adaptive evolution. 

PMID- 25608811
TI  - Mechanisms of TET protein-mediated DNA demethylation and its role in the
      regulation of mouse development.
AB  - TET (ten-eleven translocation) protein family includes three members TET1, TET2
      and TET3, which belong to alpha-ketoglutaric acid ( alpha-KG )- and Fe(2+)
      dependent dioxygenase superfamily, and have the capacity to convert 5
      methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC)
      and 5-carboxylcytosine (5 caC). At present, growing lines of evidence indicate
      that TET proteins are involved in the control of active or passive DNA
      demethylation via different mechanisms; moreover, their activities may be
      regulated by some cellular factors. TET proteins play vital roles in modulating
      mammal development, including primordial germ cell formation, embryonic
      development, stem cells pluripotency, nerve and brain development, etc. The
      identification of biological roles of TET proteins will open a new field in
      epigenetic research, and these studies on TET proteins are of great significance
      to life science research. Here, we review TET proteins from their structure,
      molecular mechanisms of DNA demethylation and function in the regulation of mouse
      development, which may provide the basis for understanding the functions of TET
      proteins. 

PMID- 25608812
TI  - Genetic screening of a pedigree with osteogenesis imperfecta type I and
      identification of a novel mutation in COL1A2 pathogenic gene.
AB  - To uncover the molecular pathogenic mechanism of congenital osteogenesis
      imperfecta (OI) type I, all the 103 exons of the COL1A1 (Collagen, type I, alpha
      1) and COL1A2 (Collagen, type I, alpha 2) genes in a child with OI type I were
      screened using PCR-DNA direct sequencing. The results showed no pathological
      mutation in COL1A1 gene, but a novel mutation c.946G>T/p.G316C in the exon 19 of
      COL1A2 gene, which was inherited from her father. This mutation was not found in
      her mother and other six phenotypically normal relatives. By denaturing high
      performance liquid chromatography (DHPLC) screening, the abnormal double-peak was
      visualized in PCR products of exon 19 of COL1A2 gene in the proband and her
      father, while the normal single-peak was shown in those of her mother and all the
      healthy controls. Using allele specific amplification (ASA) screening, a specific
      band of 391 bp in COL1A2 exon 19 was amplified only in the proband and her
      father, but not in other samples. The amino acid encoded by the mutation site is
      evolutionarily highly conserved, and this mutation was a "damaging" or "probably
      damaging" factor to OI type I, based on the predicting results using SIFT and
      Polyphen-2 softwares. In conclusion, the novel c.946G>T/p.G316C mutation in
      COL1A2 gene is a pathogenic mutation that could result in OI type I. If the
      couple wants to get pregnant again, it is necessary to screen the mutation site
      in COL1A2 gene through the prenatal genetic diagnosis in the first trimester or
      through preimplantation genetic diagnosis (PGD) in the progestation. 

PMID- 25608813
TI  - Correlation between FUT4 expression and its promoter methylation in HaCaT cells.
AB  - The expression level of fucosyltransferase IV (FUT4) is low in normal cells. The
      mechanism underlying regulation of FUT4 expression in normal cells remains
      elusive. In this study, Western blot, immunofluorescence and real-time PCR were
      used to analyze FUT4 expression in the immortalized human keratinocytes cells
      HaCaT. Methylated-specific PCR was used to investigate methylation status of FUT4
      promoter. The results showed that the FUT4 expression level was significantly
      lower in HaCaT cells than squamous carcinoma cells A431 and SCC12. FUT4 mRNA
      expression was increased in HaCaT cells treated by 5-aza-dC (5 MUmol/L), an
      inhibitor of DNA methyltransferase. Furthermore, using the primers to amplify the
      methylated fragment yielded PCR products and no products were yielded by the
      primers to amplify the unmethylated fragment in HaCaT cells. Unmethylated PCR
      products were obtained in HaCaT cells treated by 5-aza-dC, while methylated PCR
      products were not detected. These results suggest that the lower expression of
      FUT4 in HaCaT cells may be correlated with the methylation of CpG island in FUT4
      promoter. 

PMID- 25608814
TI  - Improving gene targeting efficiency on pig IGF2 mediated by ZFNs and CRISPR/Cas9
      by using SSA reporter system.
AB  - IGF2 (Insulin-like growth factor 2) is a major growth factor affecting porcine
      fetal and postnatal development. We propose that the precise modification of IGF2
      gene of Chinese indigenous pig breed--Lantang pig by genome editing technology
      could reduce its backfat thickness, and increase its lean meat content. Here, we
      tested the genome editing activities of zinc finger nucleases (ZFNs) and
      CRISPR/Cas9 system on IGF2 gene in the Lantang porcine fetal fibroblasts (PEF).
      The results indicated that CRISPR/Cas9 presented cutting efficiency up to 9.2%,
      which was significantly higher than that generated by ZFNs with DNA cutting
      efficiency lower than 1%. However, even by using CRISPR/Cas9, the relatively
      lower percentage of genetically modified cells in the transfected population was
      not satisfied for somatic nuclear transfer (SCNT). Therefore, we used a SSA
      (Single-strand annealing) reporter system to enrich genetically modified cells
      induced by ZFN or CRISPR/Cas9. T7 endonuclease I assay revealed that this
      strategy improved genome editing activity of CRISPR/Cas9 by 5 folds, and was even
      more effective for improving genome editing efficiency of ZFN. 

PMID- 25608815
TI  - Gene expression analysis of porcine peripheral blood mononuclear cell in response
      to immune stimulation of Poly I:C.
AB  - Polyinosinic-polycytidylic acid (Poly I:C) is an analogue of natural double
      strand RNA (dsRNA), which can simulate the viral dsRNA and stimulate the immune
      response. In the present study, peripheral blood mononuclear cells (PBMC) were
      isolated from piglets of Dapulian and Landrace with different disease resistance,
      and stimulated with 20 MUg/mL Poly I:C for 24 hours in vitro culture. The
      expression of several cytokines (IL6, IL8, TNFalpha, IL10, IRF3, IFNalpha and
      IFNgamma) and three pattern recognition receptors (TLR3, TLR4 and RIG1) was
      determined by qRT-PCR. The results showed that, most of the cytokines or
      receptors had obvious expression change compared with the control (without Poly
      I:C stimulation), especially the three cytokine genes IL6, IL8 and IL10, whose
      average expression change times were 20.71, 10.87 and 5.18, respectively.
      Expression comparison between breeds and among individuals of the same breed
      indicated that there was obvious difference not only between Dapulain and
      Landrace (Dapulain higher than Landrace) but also among the three individuals of
      the same breed. Our study simulated the infection of dsRNA to host cells using
      Poly I:C, and provided experimental foundation for further study on selecting the
      immune genes in response to Poly I:C stimulation and identifying the unique
      disease-resistance genes of Dapulian. 

PMID- 25608816
TI  - PPARgamma links maternal malnutrition and abnormal glucose and lipid metabolism
      in the offspring of mice.
AB  - Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear
      receptor proteins that regulate gene transcription. PPARs play essential roles in
      modulating cell differentiation, development, and metabolism (carbohydrate,
      lipid, protein). Here, we investigated whether PPARgamma plays a role in linking
      maternal malnutrition and aberrant metabolism in the offspring of mice. After
      feeding dams with high fat (HF) and low protein (LP) diet during pregnancy and
      lactation, we examined the effects on the offspring at weaning (age of 3-week).
      The results showed that the LP offspring had lower body weight and length than
      the control. The HF offspring had heavier body weight and longer body length than
      LP. The blood glucose levels in HF group were significantly higher at 30 min and
      60 min after intraperitoneal glucose administration and the area under curve was
      also significantly larger than the control. The blood glucose levels in HF group
      were significantly higher at 30 min than LP. HF group had elevated total
      cholesterol levels and LP group had decreased total cholesterol levels compared
      with the control. All results were statistically significant as examined by t
      test. More importantly, PPARgamma expression levels detected by qRT-PCR were
      significantly increased in HF and LP groups compared with the control. In
      conclusion, maternal HF and LP diet during pregnancy and lactation can induce
      impaired glucose and lipid metabolism in the early life of mouse offspring, where
      PPARgamma may play an important role. 

PMID- 25608817
TI  - Comparative analysis of H3K9 acetylation level in parthenogenetic, and in vitro
      and in vivo developed mouse embryos.
AB  - The developmental rate of parthenogenetic embryos is slower than that of embryos
      generated in vitro and in vivo. To detect the effects of epigenetic modification
      on embryo development, we compared the H3K9 acetylation level in these three
      types of embryos as well as parthenogenetic embryos treated with a histone
      deacetylase inhibitor trichostatin (TSA) by indirect immunofluorescence. Our
      results showed that fluctuations in the level of acetylated H3K9 detected during
      embryo development are similar among different types of mouse embryos. However,
      the level of H3K9 acetylation in parthenogenetic embryos is significantly higher
      while the level in embryos generated in vitro is lower when compared with that in
      embryos derived from in vivo. Treatment of parthenogenetic embryos with TSA
      increases the developmental rate but further elevates the level of H3K9
      acetylation, especially from pronuclear to 8-cell stages. These results suggest
      that the promoters of genes that should be silenced during pre-implantation
      embryo development may be hyperacetylated in parthenogenetic embryos which
      inhibit normal embryo development. However, the positive effect of TSA on embryo
      development is not through altering the H3K9 acetylation level. 

PMID- 25608818
TI  - Cloning and characterization of a salt responsive gene AcPsbQ1 from Atriplex
      canescens.
AB  - PsbQ is an extrinsic subunit of the photosystem II in eukaryotic photosynthetic
      organisms. Numerous studies have demonstrated that PsbQ can stabilize the
      inorganic cofactors and enhance the oxygen release in PSII. The decrease of
      photosynthesis rate under salinity condition is normally attributed to the high
      concentration of injurious ions, such as Na(+) and Cl(-), which accumulate in the
      chloroplast and damage thylakoid membrane under salinity stress. In this study,
      AcPsbQ1 was isolated from a halophyte Atriplex canescens cDNA library. The
      AcPsbQ1 contains an open reading frame of 699 bp encoding a 233 amino acid
      protein. In order to investigate its function, AcPsbQ1 was cloned and transformed
      into Saccharomyces cerevisiae INVSc1. The heterologous expression of AcPsbQ1 in
      transgenic yeast significantly helped to increase the adapting and recovery
      ability of yeast cells under the salt and drought. Quantitative real-time PCR
      assay was performed to reveal the expression pattern of AcPsbQ1 under different
      abiotic stresses. On exposure to NaCl stress, the transcript level of AcPsbQ1 was
      significantly enhanced. AcPsbQ1 expression level was also up-regulated under
      drought stress. These results indicated that AcPsbQ1 might involve in the
      response to salt stress in A. canescens. 

PMID- 25608819
TI  - MapGene2Chrom, a tool to draw gene physical map based on Perl and SVG languages.
AB  - Genetic linkage map is helpful for analysis on heredity of some gene families and
      map-based gene cloning because of its simple and elegant manifestation. One
      software is in need to draw a gene physical map, which shows a manner similar to
      the genetic linkage map, based on the relative physical distance between genes.
      Although some tools like GBrowse and MapViewer etc. are available to draw gene
      physical map, there are obvious limitations for them: (1) the data need to be
      decorated in advance; (2) users can't modify results. Therefore, we developed a
      bio-assisted mapping software--MapGene2Chrom with PC and web versions, which is
      based on Perl and SVG languages. The software can be used to draw the
      corresponding physical map quickly in SVG format based on the input data. It will
      become a useful tool for drawing gene physical map with the advantages of simple
      input data format, easily modified output and very good portability. 

PMID- 25608820
TI  - Understanding the cellular and molecular mechanisms of dominant and recessive
      inheritance in genetics course.
AB  - In Mendellian genetics, the dominance and recessiveness are used to describe the
      functional relationship between two alleles of one gene in a heterozygote. The
      allele which constitutes a phenotypical character over the other is named
      dominant and the one functionally masked is called recessive. The definitions
      thereby led to the creation of Mendel's laws on segregation and independent
      assortment and subsequent classic genetics. The discrimination of dominance and
      recessiveness originally is a requirement for Mendel's logical reasoning, but now
      it should be explained by cellular and molecular principles in the modern
      genetics. To answer the question raised by students of how the dominance and
      recessiveness are controlled, we reviewed the recent articles and tried to
      summarize the cellular and molecular basis of dominant and recessive inheritance.
      Clearly, understanding the essences of dominant and recessive inheritance
      requires us to know the dissimilarity of the alleles and their products (RNA
      and/or proteins), and the way of their function in cells. The alleles spatio
      temporally play different roles on offering cells, tissues or organs with
      discernible phenotypes, namely dominant or recessive. Here, we discuss the
      changes of allele dominance and recessiveness at the cellular and molecular
      levels based on the variation of gene structure, gene regulation, function and
      types of gene products, in order to make students understand gene mutation and
      function more comprehensively and concretely. 

PMID- 25608821
TI  - Added value of advanced over conventional magnetic resonance imaging in grading
      gliomas and other primary brain tumors.
AB  - BACKGROUND: Although conventional MR imaging (MRI) is the most widely used non
      invasive technique for brain tumor grading, its accuracy has been reported to be
      relatively low. Advanced MR techniques, such as perfusion-weighted imaging (PWI),
      diffusion-weighted imaging (DWI), and magnetic resonance spectroscopy (MRS),
      could predict neoplastic histology, but their added value over conventional MRI
      is still open to debate. METHODS: We prospectively analyzed 129 patients
      diagnosed with primary brain tumors (118 gliomas) classified as low-grade in 30
      cases and high-grade in 99 cases. RESULTS: Significant differences were obtained
      in high-grade tumors for conventional MRI variables (necrosis, enhancement,
      edema, hemorrhage, and neovascularization); high relative cerebral blood volume
      values (rCBV), low relative apparent diffusion coefficients (rADC), high ratio of
      N-acetyl-aspartate/creatine at short echo time (TE) and high choline/creatine at
      long TE. Among conventional MRI variables, the presence of enhancement and
      necrosis were demonstrated to be the best predictors of high grade in primary
      brain tumors (sensitivity 95.9%; specificity 70%). The best results in primary
      brain tumors were obtained for enhancement, necrosis, and rADC (sensitivity
      98.9%; specificity 75.9%). Necrosis and enhancement were the only predictors of
      high grade in gliomas (sensitivity 97.6%; specificity 76%) when all the magnetic
      resonance variables were combined. CONCLUSIONS: MRI is highly accurate in the
      assessment of tumor grade. The combination of conventional MRI features with
      advanced MR variables showed only improved tumor grading by adding rADC to
      conventional MRI variables in primary brain tumors.

PMID- 25608822
TI  - Paraneoplastic thrombocytosis independently predicts poor prognosis in patients
      with locally advanced pancreatic cancer.
AB  - BACKGROUND AND AIMS: Platelets are believed to promote tumor growth and
      metastasis but their prognostic role in locally advanced pancreatic cancer (LAPC)
      remains largely unknown. We assessed whether pretreatment platelet counts
      independently predict survival outcomes in patients with LAPC treated with
      chemoradiation (CRT). METHODS: We retrospectively reviewed the MD Anderson
      pancreatic cancer database and identified 199 patients with LAPC treated with CRT
      between 2006 and 2012. Induction chemotherapy was used prior to consolidative CRT
      in 177 (89%) patients. Median radiation dose was 50.4 Gy. Concurrent
      radiosensitizers were gemcitabine-based (13%) or capecitabine-based (84%)
      regimens. Actuarial univariate and multivariate statistical methods were used to
      determine significant prognostic factors for overall survival (OS) and
      progression-free survival (PFS) calculated from the start of treatment. RESULTS:
      Median follow-up was 9.9 months. Median OS and PFS durations were 17.7 and 10.7
      months, respectively. On univariate analysis, platelet count > 300 K/MUl, KPS <=
      80, >= 5% weight loss and pretreatment CA19-9 above the median were associated
      with inferior OS or PFS. Median OS was lower in patients with platelet count >
      300 K/MUl compared to patients with platelet count <= 300 K/MUl (10.2 vs. 19
      months; p = 0.0002). Corresponding median PFS times were 7.8 months and 11.1
      months (p = 0.004), respectively. On multivariate analysis, platelet count > 300
      K/MUl (p = 0.012), >= 5% weight loss (p = 0.002) and elevated pretreatment CA19-9
      (p = 0.005) were independent prognostic factors for OS. Platelet count > 300
      K/MUl (p = 0.03) and KPS <= 80 (p = 0.05) independently predicted PFS.
      CONCLUSIONS: Our analysis suggests that pretreatment thrombocytosis independently
      predicts inferior OS and PFS in LAPC.

PMID- 25608823
TI  - Does the timing of adjuvant chemotherapy for gastric cancer influence patient
      outcome?

PMID- 25608824
TI  - Cancer risk and mortality in asthma patients: A Swedish national cohort study.
AB  - BACKGROUND: Previous studies found an increased risk of cancer in hospitalized
      asthma patients, but it is not known whether patients from primary health care
      show a similar risk pattern. In addition, it is unclear whether the diagnosis of
      asthma can influence the prognosis of subsequent cancer. METHODS: Asthma patients
      were identified from Swedish inpatient, outpatient, and primary health care
      registers, and were linked to the Swedish Cancer Registry to identify subsequent
      diagnoses of cancer. Standardized incidence ratios (SIRs) were used to examine
      the risk of cancer in asthma patients compared with subjects without asthma. In
      addition, we used Cox proportional hazards regression to estimate hazard ratios
      (HRs) for mortality in patients with both asthma and cancer. RESULTS: A total of
      10 649 cancers were diagnosed in patients with previous asthma, with a SIR of
      1.19 (95% CI 1.17-1.21). A total of 15 cancer sites showed an increased
      incidence, whereas two cancer sites showed a decreased risk. Non-allergic asthma
      showed the highest risk of cancer (SIR = 1.25, 95% CI 1.18-1.32), followed by
      unspecified asthma (SIR = 1.22, 95% CI 1.19-1.25), status asthmaticus (SIR =
      1.19, 95% CI 1.02-1.39), and allergic asthma (SIR = 1.14, 95% CI 1.06-1.22). The
      risk of cancer was similarly increased in asthma patients diagnosed in primary
      health care and those diagnosed in hospitals. Cancer patients with previous
      asthma had increased mortality, with a HR of 1.55 (95% CI 1.50-1.60). HRs ranged
      from 1.09 to 1.94 for different sites/types of cancer. CONCLUSIONS: Patients with
      asthma, irrespective of whether they were treated in primary health care or
      hospitals, had an increased risk of cancer. In addition, cancer patients with
      previous asthma had a worse prognosis compared with those without asthma,
      suggesting that these patients may require a multidisciplinary approach to manage
      the comorbidity.

PMID- 25608825
TI  - Motivation for the inclusion of genetic risk factors of radiosensitivity
      alongside dosimetric and clinical parameters in predicting normal tissue effects.

PMID- 25608826
TI  - Thrombocytopenia due to low-dose colchicine therapy: A possible drug interaction
      with nivolumab and implications for supportive care.

PMID- 25608827
TI  - A long and distant journey: a case of rectal cancer with metastasis to the orbit.
AB  - We present the case of a 33-year-old man with acute onset of eye pain and
      diplopia as the presenting symptoms of rectal cancer with orbital metastasis.
      Colorectal cancer with orbital metastasis is exceedingly rare with only 7 cases
      worldwide despite the prevalence of colorectal cancer. The rarity of this
      presentation may be related to the long path through multiple vascular beds that
      tumor emboli from the rectum must travel in order to reach the orbit.

PMID- 25608828
TI  - A nonsynonymous SNP in BANK1 is associated with serum LDL cholesterol levels in
      three Korean populations.
AB  - Serum levels of lipids, such as cholesterol and triglycerides, are heritable risk
      factors for cardiovascular disease and targets for therapeutic intervention.
      Because previous genome-wide association studies (GWASs) did not target
      functional genetic variants, we employed an alternate approach using
      nonsynonymous single-nucleotide polymorphisms (SNPs) to identify functional
      genetic variants associated with the regulation of serum lipid levels. We
      selected 3667 healthy individuals from a rural community-based cohort (CAVAS;
      Cardio Vascular disease Association Study) of the Korean Genome and Epidemiology
      Study project. We analyzed demographic and lifestyle information, lipid
      measurements and genotypes using the Illumina-1M SNP chip. For genotyping, we
      isolated 11 558 nonsynonymous SNPs and conducted a linear regression analysis
      with four lipid traits (total, high-density lipoprotein (HDL) and low-density
      lipoprotein (LDL) cholesterols and triglycerides). Significantly associated SNPs
      were validated in two independent Korean populations, Korean Association Resource
      (KARE) (n=4116) and Health Examinee (HEXA) (n=2178). Of the 11 558 SNPs, one SNP
      (rs3733197) from the CAVAS was significantly associated with serum LDL
      cholesterols (beta+/-s.e.=4.67+/-0.94, P-value=1.0 * 10(-6 and) Bonferroni
      corrected P-value=0.012). The replication results of HEXA and KARE were beta+/
      s.e.=2.88+/-1.12, P-value=0.016 and beta+/-s.e.=1.26+/-0.97, P-value=0.196,
      respectively. An overall meta-analysis of the three data sets revealed
      beta=2.98+/-0.57, P-value=6.19 * 10(-7). The rs3733197 is located in the coding
      region of BANK1 (B-cell scaffold protein with ankyrin repeats 1), and the minor
      allele (A) resulted in the replacement of the Alanine at position 383 with
      Threonine. 

PMID- 25608829
TI  - Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean
      population by genome-wide association studies including gene-environment
      interactions.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial
      disease. Although smoking is a main risk factor for obstructive impairment, not
      all smokers develop this critical disease. We conducted a genome-wide association
      study to identify the association between genetic variants and pulmonary function
      and also examined how these variants relate to lung impairment in accordance with
      smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319)
      and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we
      analyzed the association between genetic variants (single-nucleotide
      polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using
      multivariate linear regression models. Similar analyses were conducted after
      stratification by smoking status. Four genome-wide significant signals in the
      FAM13A gene (the strongest signal at rs2609264, P=1.76 * 10(-7) in a combined
      set) were associated with FEV1/FVC. For the association with ratio, the effect
      size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 * 10(
      7)) as compared with the TCAG haplotype (reference haplotype) in a combined set.
      There was also a significant interaction of FAM13A haplotypes with heavy smoking
      on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported
      association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes
      also interacted with heavy smoking to affect the risk of reduced pulmonary
      function. 

PMID- 25608830
TI  - Rare cases of congenital arthrogryposis multiplex caused by novel recurrent CHRNG
      mutations.
AB  - Multiple pterygium syndrome (MPS) is an autosomal recessively inherited condition
      that becomes evident before birth, with pterygium at multiple joints and
      akinesia. There are two forms of this syndrome that are differentiated by
      clinical severity: the milder form, Escobar type (OMIM#265000), and the more
      severe form, lethal type (OMIM#253290). Mutations in CHRNG, which encode the
      acetylcholine receptor gamma subunit, cause most cases of MPS. Here, we present
      three patients from two unrelated families showing multiple joint contractures in
      both the upper and lower limbs. High-arched palates with malocclusion, short neck
      and micrognathia were observed in all patients. Peripheral blood karyotypes were
      normal. Whole-exome sequencing analysis of the patients' genomes led to the
      discovery of identical missense (p.Pro143Arg) and frameshift deletion variants
      (p.Pro251fs*45) on CHRNG. These were rare cases of congenital arthrogryposis
      multiplex related to novel recessive CHRNG variants in two Korean kindred without
      apparent relatedness. 

PMID- 25608831
TI  - Identical deletion at 14q13.3 including PAX9 and NKX2-1 in siblings from
      mosaicism of unaffected parent.
AB  - By screening patients with undiagnosed multiple congenital anomalies and
      intellectual disability using array-comparative genomic hybridization, we
      identified an 884 kb heterozygous microdeletion at 14q13.3 in two siblings
      presenting with oligodontia, hypothyroidism and persistent pulmonary hypertension
      of the newborn, resulting from their parental gonosomal mosaicism. Among the six
      genes included in the deletion, haploinsufficiency of PAX9 and NKX2-1 was
      probably associated with their phenotypes. These results highlighted a
      possibility of recurrence of pathogenic copy-number variants associated with
      parental mosaicism, which requires careful genetic counseling. 

PMID- 25608833
TI  - Fluorescent and colorimetric ion probes based on conjugated oligopyrroles.
AB  - Metal ions and anions play important roles in many industrial and biochemical
      processes, and thus it is highly desired to detect them in the relevant systems.
      Small organic molecule based sensors for selective and sensitive detection of
      target ions show the advantages of low cost, high sensitivity and convenient
      implementation. In this area, pyrrole has incomparable advantages. It can be
      easily incorporated into linear and macrocyclic conjugated structures such as
      dipyrrins, porphyrins, and N-confused porphyrins, which may utilize the imino N
      and amino NH moieties for binding metal ions and anions, respectively. In this
      tutorial review, we focus on representative examples to describe the design,
      syntheses, sensing mechanisms, and applications of the conjugated oligopyrroles.
      These compounds could be used as colorimetric or fluorescent ion probes, with the
      advantages of vivid colour and fluorescence changes, easy structural modification
      and functionalization, and tunable emission wavelengths. Compared with normal
      porphyrins, simple di- and tripyrrins, as well as some porphyrinoids are more
      suitable for designing fluorescence "turn-on" metal probes, because they may
      exhibit flexible confirmations, and metal coordination will improve the rigidity,
      resulting in vivid fluorescence enhancement. It is noteworthy that the
      oligopyrrolic moieties may simultaneously act as the binding unit as well as the
      reporting moiety, which simplifies the design and syntheses of the probes. 

PMID- 25608832
TI  - Detecting copy-number variations in whole-exome sequencing data using the eXome
      Hidden Markov Model: an 'exome-first' approach.
AB  - Whole-exome sequencing (WES) is becoming a standard tool for detecting nucleotide
      changes, and determining whether WES data can be used for the detection of copy
      number variations (CNVs) is of interest. To date, several algorithms have been
      developed for such analyses, although verification is needed to establish if they
      fit well for the appropriate purpose, depending on the characteristics of each
      algorithm. Here, we performed WES CNV analysis using the eXome Hidden Markov
      Model (XHMM). We validated its performance using 27 rare CNVs previously
      identified by microarray as positive controls, finding that the detection rate
      was 59%, or higher (89%) with three or more targets. XHMM can be effectively
      used, especially for the detection of >200 kb CNVs. XHMM may be useful for
      deletion breakpoint detection. Next, we applied XHMM to genetically unsolved
      patients, demonstrating successful identification of pathogenic CNVs: 1.5-1.9-Mb
      deletions involving NSD1 in patients with unknown overgrowth syndrome leading to
      the diagnosis of Sotos syndrome, and 6.4-Mb duplication involving MECP2 in
      affected brothers with late-onset spasm and progressive cerebral/cerebellar
      atrophy confirming the clinical suspect of MECP2 duplication syndrome. The
      possibility of an 'exome-first' approach for clinical genetic investigation may
      be considered to save the cost of multiple investigations. 

PMID- 25608834
TI  - Histomorphological and torque removal comparison of 6 mm orthodontic miniscrews
      with and without surface treatment in New Zealand rabbits.
AB  - AIM: The purpose of this study was to assess the difference of removal torque
      values (RTV) and the bone-to-implant contact (BIC) between the sand-blasted,
      large grit, and acid-etched (SLA) surface-treated and the machined surface (MA)
      miniscrews. MATERIAL AND METHODS: Miniscrews used in this study were 6mm long
      with a diameter of 1.5mm. A total of 23 SLA miniscrews and 24 MA miniscrews were
      placed into the distal femoral condyle of 24 New Zealand rabbits. Removal torque
      test and the BIC was histologically evaluated at 0 and 8 weeks. RESULTS: There
      was no statistical difference between the RTV in the MA group versus the SLA
      group at both 0 and 8 weeks. Comparing 0-8 weeks, there was no significant
      difference in RTV of the SLA group (P = 0.48), however the change in the MA group
      was statistically significant (P = 0.006). Histological observation showed a
      significant decrease in BIC comparing 0 and 8 weeks for the MA group. The BIC
      ratio at 8 weeks was statistically significantly higher in the SLA group compared
      to the MA group. CONCLUSION: SLA surface preparation does not increase the RTV of
      miniscrews. Further investigations under loading and a large sample size are
      required.

PMID- 25608835
TI  - Global health agenda on non-communicable diseases: has WHO set a smart goal for
      physical activity?

PMID- 25608836
TI  - ATM may be a protective factor in endometrial carcinogenesis with the
      progesterone pathway.
AB  - The purpose of the study was to explore the role and mechanism of ataxia
      telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse
      phase protein array (RPPA) was used to analyze the expression of ATM signal
      pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM
      expression was detected in endometrium specimens by immunohistochemistry,
      including 8 cases with proliferative endometrium, 6 cases with secretory
      endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex
      hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83
      cases with type I endometrial cancer. The relationship between ATM expression and
      other clinicopathological indicators was also examined in type I endometrial
      cancer patients. The mechanisms of ATM were explored in vitro with the
      endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test
      and Western blot analysis were performed to test proliferation and protein
      expression. Statistical analysis was performed with SPSS19.0. The significance
      level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA)
      stimulation in Ishikawa in RPPA. ATM expression gradually decreased in
      endometrial hyperplasic lesions compared with the normal proliferative and
      secretory endometrium and was the lowest in type I endometrial cancer. ATM
      expression was negatively correlated with pathological grades in type I
      endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in
      Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA
      stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA
      might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53
      caspase-3 (active), preserving normal endometrium and protecting it from
      malignancies. ATM might be a promising indicator for endometrial hyperplasia and
      cancer. 

PMID- 25608837
TI  - The tumor suppressor protein p150(Sal2) in carcinogenesis.
AB  - The transcription factor p150(Sal2), the product of the SALL2 gene, was first
      identified as a binding target of the oncogenic mouse polyomavirus T antigen.
      However, mouse polyomavirus is not the only oncogenic virus that targets
      p150(Sal2); the human papillomavirus E6 protein also targets this cellular
      protein in order to overcome p150(Sal2)-mediated growth arrest. Studies have
      demonstrated that p150(Sal2) recognizes GC-rich regions of the promoter and
      transcriptionally induces p21(Cip1/Waf1) and BAX in human ovarian epithelial
      cancer cells, resulting in cell growth arrest and apoptosis. Although the
      p150(Sal2) protein is strongly expressed in surface epithelial cells of the
      ovary, immunostaining experiments showed that expression of p150(Sal2) was lost
      in 90 % of 210 human ovarian carcinomas, supporting an important tumor
      suppressive role for p150(Sal2) in the human ovary. Mechanisms of silencing SALL2
      in OVCA cell lines and primary tumors and possible therapeutic approaches for
      ovarian carcinoma are discussed in this review. 

PMID- 25608838
TI  - TIMP-1 and CEA as biomarkers in third-line treatment with irinotecan and
      cetuximab for metastatic colorectal cancer.
AB  - KRAS wild-type (wt) status determines indication for treatment with combination
      therapy, including epidermal growth factor receptor (EGFR) inhibitors, but still,
      the overall response rate in KRAS wt patients is less than 40 %. Consequently,
      the majority of patients will suffer from substantial side effects and no
      apparent benefit. Tissue inhibitor of metalloproteinases-1 is a glycoprotein,
      which regulates metalloproteinases and may consequently imply a central role in
      tumour progression. Furthermore, it is closely related to the EGFR regulation and
      has shown promising potential as a biomarker in colorectal cancer (CRC). The aim
      of the present study was to investigate the clinical value of TIMP-1 in patients
      with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan.
      Patients with chemotherapy-resistant mCRC referred to third-line treatment with
      cetuximab (initial 400 mg/m(2) followed by weekly 250 mg/m(2))/irinotecan (350
      mg/m(2) q3w) were prospectively included in the biomarker study, as previously
      published. Pre-treatment blood samples were collected, and plasma TIMP-1 was
      measured by a validated in-house ELISA assay. In addition, carcinoembryonic
      antigen (CEA) measurement was performed with a standardised method. A total of
      107 patients were included in the biomarker study. The median baseline plasma
      TIMP-1 level was 271.1 ng/ml (range 65.9-1432 ng/ml) with no significant
      associations with baseline clinical characteristics. Median baseline plasma TIMP
      1 levels were significantly higher in patients with early progression compared to
      patients who achieved disease control, 349 ng/ml (233-398 95 % confidence
      interval (CI)) and 215 ng/ml (155-289 95 % CI), respectively, p = 0.03,
      suggesting some association with treatment efficacy. When dividing patients
      according to TIMP-1 tertiles, the median progression-free survival (PFS) in
      patients with a high level of TIMP-1 was 2.4 months (95 % CI 2.1-4.1) compared to
      3.3 months (95 % CI 2.1-6.2) and 4.7 months (95 % 3.2-7.6) in patients with
      intermediate or low levels, respectively. Analysis of TIMP-1 as a continuous
      variable revealed a shorter PFS associated with increasing levels of TIMP-1
      (hazard ratio (HR) 1.36). These results translated into a significantly lower
      overall survival (OS) in patients with a high baseline TIMP-1 level (4.5 months
      (95 % CI 3.4-5.4)), compared to those with intermediate or low TIMP-1 levels (7.8
      months (95 % CI 4.4-13.7) and 12.0 months (95 % CI 10.1-14.3), respectively, p <
      0.0001). An 83 % higher hazard for death was revealed (HR = 1.83) with each
      twofold increase in the TIMP-1 level. Pre-treatment levels of CEA were not
      associated with any of the baseline characteristics (except primary tumour
      localisation) or to differences in PFS or OS. The rank correlation between CEA
      and TIMP-1 was r = 0.50, and a test for interaction between TIMP-1 and CEA
      (dichotomised at 5 ng/ml) in survival analysis was not significant (p = 0.18). A
      multivariate analysis for PFS and OS resulted in a model with significant
      contributions from TIMP-1, KRAS, and the number of metastatic sites. We have
      confirmed the potential prognostic value of TIMP-1 measurement prior to
      palliative chemotherapy for mCRC. However, validation in randomised trials will
      be essential with the perspective of establishing a potential predictive role of
      plasma TIMP-1 in this setting.

PMID- 25608839
TI  - SOX11 expression in chronic lymphocytic leukemia correlates with adverse
      prognostic markers.
AB  - The transcription factor SOX11 plays an important role in embryonic neurogenesis
      and tissue remodeling. Recent studies have shown aberrant expression of SOX11 in
      various types of aggressive B cell neoplasms. In this study, we have analyzed
      SOX11 transcription levels in 86 patients with diagnosis of chronic lymphocytic
      leukemia (CLL). Results were correlated with well-known prognostic factors such
      as immunoglobulin heavy chain variable (IGHV) gene mutational status,
      cytogenetics risk groups and clinicopathological characteristics of the disease.
      Overall, 35 % of cases showed SOX11 expression; meanwhile, the remaining 65 %
      lacked gene expression. The analysis taking into account the IGHV mutational
      status showed significant differences in SOX11 transcripts levels between mutated
      (0.004 +/- 0.0001) and unmutated CLL patients (0.405 +/- 0.011) (p < 0.0001), as
      well as a positive correlation between SOX11 mRNA expression and the percentage
      of IGHV homology (p = 0.0001). Furthermore, significantly lower SOX11 mRNA
      expression was detected in patients with deletion 13q14 as a single alteration
      (0.016 +/- 0.008) than those observed in cases with deletions 11q/17p (0.35 +/-
      0.017) (p = 0.02). The correlation of gene expression with clinical evolution
      showed shorter treatment free survival (p = 0.043) and overall survival (p =
      0.047) in SOX11 positive patients compared to SOX11 negative cases. Our findings
      show for the first time an association between SOX11 expression and some CLL poor
      prognostic factors. These results suggest SOX11 as a possible biomarker that adds
      new biological information that could contribute to a better understanding of
      this pathology.

PMID- 25608840
TI  - MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by
      targeting PIK3R3.
AB  - MicroRNAs (miRNAs) are critical for cancer development and progression.
      Elucidating the underlying mechanism of miRNAs in carcinogenesis may lead to
      novel diagnostic and therapeutic strategies for malignancy. In this study, we
      found that miR-511 expression was markedly downregulated in hepatocellular
      carcinoma (HCC) cell lines and tissues. Phosphoinositide-3-kinase regulatory
      subunit 3 (PIK3R3) was identified as a direct target of miR-511 and miR-511
      expression inversely correlated with PIK3R3 mRNA expression in clinical HCC
      tissues. We further demonstrated that miR-511 suppressed HCC cell proliferation,
      migration, and invasion by repressing PIK3R3 expression. Investigations of
      possible mechanisms underlying these results revealed that miR-511 inhibited the
      phosphorylation of AKT and mTOR, which are key participants in the AKT/mTOR
      pathway. Taken together, our findings provide new insights into tumor suppression
      by miR-511 by negatively regulating the PIK3R3/AKT/mTOR signaling pathway.

PMID- 25608841
TI  - Combined Runx2 and Snail overexpression is associated with a poor prognosis in
      breast cancer.
AB  - The purpose of this study was to investigate the prognostic value of Runx2 and
      Snail expression in breast cancer. The expression of Runx2 and Snail in clinical
      specimens from 125 breast cancer patients was detected by immunohistochemistry.
      The results showed there is a link between Runx2 and Snail expression at protein
      levels (p = 0.007). The Kaplan-Meier survival analysis showed that Runx2 or Snail
      expression was correlated with shortened disease-free survival (DFS) (p = 0.002,
      p = 0.004, respectively) and overall survival (OS) (p = 0.002, p = 0.009,
      respectively). In addition, Runx2-positive/Snail-positive patients had the worst
      DFS and OS (p = 0.001, p < 0.001, respectively). In multivariate survival
      analysis, Runx2, Snail, and combined Runx2/Snail were still remained as
      independent prognostic factors for DFS (p = 0.020, p = 0.013, and p = 0.001,
      respectively) and OS (p = 0.027, p = 0.030 and p = 0.005, respectively). These
      results suggest that a combined Runx2/Snail expression could be used as a new
      significant prognostic biomarker for patients with breast cancer.

PMID- 25608842
TI  - In vitro detection of circulating tumor cells compared by the CytoTrack and
      CellSearch methods.
AB  - Comparison of two methods to detect circulating tumor cells (CTC) CytoTrack and
      CellSearch through recovery of MCF-7 breast cancer cells, spiked into blood
      collected from healthy donors. Spiking of a fixed number of EpCAM and pan
      cytokeratin positive MCF-7 cells into 7.5 mL donor blood was performed by
      FACSAria flow sorting. The samples were shipped to either CytoTrack or CellSearch
      research facilities within 48 h, where evaluation of MCF-7 recovery was
      performed. CytoTrack and CellSearch analyses were performed simultaneously.
      Recoveries of MCF-7 single cells, cells in clusters, and clusters were
      determined. The average numbers of MCF-7 cells/cells in clusters/clusters
      recovered from blood by the CytoTrack and CellSearch methods were 103 +/- 5.9/27
      +/- 7.9/11 +/- 3.5 (95 % CI) and 107 +/- 4.4/20 +/- 7.1/10 +/- 3.5, respectively,
      with no difference between the two methods (p = 0.37/p = 0.23/p = 0.09). Overall,
      the recovery of CytoTrack and CellSearch was 68.8 +/- 3.9 %/71.1 +/- 2.9 %,
      respectively (p = 0.58). In spite of different methodologies, CytoTrack and
      CellSearch found similar number of CTCs, when spiking was performed with the
      EpCAM and pan cytokeratin-positive cell line MCF-7. The results suggest that
      CytoTrack and CellSearch have similar abilities to identify CTC in vitro.

PMID- 25608843
TI  - Conformation of a charged vesicle.
AB  - We report on the first systematic study of vesicle conformational change caused
      by Coulomb interaction between surface charges on a lipid vesicle. The
      equilibrium configuration of a charged vesicle is found, as the result of the
      competition between the local bending elastic energy and the long-range
      electrostatic interaction within the membrane where the counter-ion effects are
      neglected. Because of the Rayleigh instability, a charged vesicle undergoes
      conformational transitions as a function of the surface charge density. 

PMID- 25608844
TI  - Ultrafast liquid water transport through graphene-based nanochannels measured by
      isotope labelling.
AB  - Based on isotope labelling, we found that liquid water can afford an ultrafast
      permeation through graphene-based nanochannels with a diffusion coefficient 4-5
      orders of magnitude greater than in the bulk case. When dissolving ions in
      sources, the diffusion coefficient of ions through graphene channels lies in the
      same order of magnitude as water, while the ion diffusion is slightly faster than
      water, indicating that the ions are mainly transported by water flows and the
      delicate interactions between ions and nanocapillary walls also take effect in
      the accelerated ion transportation. 

PMID- 25608845
TI  - Extracorporeal membrane oxygenation for critically ill adults.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a form of life support
      that targets the heart and lungs. Extracorporeal membrane oxygenation for severe
      respiratory failure accesses and returns blood from the venous system and
      provides non-pulmonary gas exchange. Extracorporeal membrane oxygenation for
      severe cardiac failure or for refractory cardiac arrest (extracorporeal
      cardiopulmonary resuscitation (ECPR)) provides gas exchange and systemic
      circulation. The configuration of ECMO is variable, and several pump-driven and
      pump-free systems are in use. Use of ECMO is associated with several risks.
      Patient-related adverse events include haemorrhage or extremity ischaemia;
      circuit-related adverse effects may include pump failure, oxygenator failure and
      thrombus formation. Use of ECMO in newborns and infants is well established, yet
      its clinical effectiveness in adults remains uncertain. OBJECTIVES: The primary
      objective of this systematic review was to determine whether use of veno-venous
      (VV) or venous-arterial (VA) ECMO in adults is more effective in improving
      survival compared with conventional respiratory and cardiac support. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE (Ovid) and EMBASE (Ovid) on 18 August 2014. We searched
      conference proceedings, meeting abstracts, reference lists of retrieved articles
      and databases of ongoing trials and contacted experts in the field. We imposed no
      restrictions on language or location of publications. SELECTION CRITERIA: We
      included randomized controlled trials (RCTs), quasi-RCTs and cluster-RCTs that
      compared adult ECMO versus conventional support. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened the titles and abstracts of all
      retrieved citations against the inclusion criteria. We independently reviewed
      full-text copies of studies that met the inclusion criteria. We entered all data
      extracted from the included studies into Review Manager. Two review authors
      independently performed risk of bias assessment. All included studies were
      appraised with respect to random sequence generation, concealment of allocation,
      blinding of outcome assessment, incomplete outcome data, selective reporting and
      other bias. MAIN RESULTS: We included four RCTs that randomly assigned 389
      participants with acute respiratory failure. Risk of bias was low in three RCTs
      and high in one RCT. We found no statistically significant differences in all
      cause mortality at six months (two RCTs) or before six months (during 30 days of
      randomization in one trial and during hospital stay in another RCT). The quality
      of the evidence was low to moderate, and further research is very likely to
      impact our confidence in the estimate of effects because significant changes have
      been noted in ECMO applications and treatment modalities over study periods to
      the present.Two RCTs supplied data on disability. In one RCT survival was low in
      both groups but none of the survivors had limitations in their daily activities
      six months after discharge. The other RCT reported improved survival without
      severe disability in the intervention group (transfer to an ECMO centre +/- ECMO)
      six months after study randomization but no statistically significant differences
      in health-related quality of life.In three RCTs, participants in the ECMO group
      received greater numbers of blood transfusions. One RCT recorded significantly
      more non-brain haemorrhage in the ECMO group. Another RCT reported two serious
      adverse events in the ECMO group, and another reported three adverse events in
      the ECMO group.Clinical heterogeneity between studies prevented meta-analyses
      across outcomes. We found no completed RCT that had investigated ECMO in the
      context of cardiac failure or arrest. We found one ongoing RCT that examined
      patients with acute respiratory failure and two ongoing RCTs that included
      patients with acute cardiac failure (arrest). AUTHORS' CONCLUSIONS:
      Extracorporeal membrane oxygenation remains a rescue therapy. Since the year
      2000, patient treatment and practice with ECMO have considerably changed as the
      result of research findings and technological advancements over time. Over the
      past four decades, only four RCTs have been published that compared the
      intervention versus conventional treatment at the time of the study. Clinical
      heterogeneity across these published studies prevented pooling of data for a meta
      analysis.We recommend combining results of ongoing RCTs with results of trials
      conducted after the year 2000 if no significant shifts in technology or treatment
      occur. Until these new results become available, data on use of ECMO in patients
      with acute respiratory failure remain inconclusive. For patients with acute
      cardiac failure or arrest, outcomes of ongoing RCTs will assist clinicians in
      determining what role ECMO and ECPR can play in patient care.

PMID- 25608847
TI  - Experiences of HIV-positive gay, bisexual and other men who have sex with men
      residing in relatively rural areas.
AB  - Most previous studies of the sexual behaviour of gay, bisexual and other men who
      have sex with men living with HIV are based on samples of men recruited within
      relatively urban and suburban areas of the USA. The aim of the present study was
      to explore the potential challenges associated with HIV-related stigma and
      residing in a relatively rural area. We conducted a qualitative study based in
      south-central Indiana, a relatively rural area of the USA. Twenty-three HIV
      positive gay, bisexual and other men who have sex with men, aged 21-48 years,
      were interviewed on topics regarding community engagement, perceived HIV-related
      stigma, relationship formation, sexual behaviour and HIV status disclosure.
      Findings indicate HIV-related stigma is commonly reported at the interpersonal
      and community levels. Because of this, men face complex situations on how and
      when to disclose their HIV status to members of their social and sexual networks.
      Although many participants reported many challenges associated with relationship
      formation, all expressed a desire for romantic and/or sexual connections with
      other men and/or women. Results suggest that new programmatic approaches are
      necessary to inform the work of social service and medical providers on
      mechanisms to intervene and combat stigma and discrimination inherent in
      communities, programmes and policies. 

PMID- 25608848
TI  - We need to discuss India's reliance on private medical colleges.

PMID- 25608846
TI  - Dissecting structural and electronic effects in inducible nitric oxide synthase.
AB  - Nitric oxide synthases (NOSs) are haem-thiolate enzymes that catalyse the
      conversion of L-arginine (L-Arg) into NO and citrulline. Inducible NOS (iNOS) is
      responsible for delivery of NO in response to stressors during inflammation. The
      catalytic performance of iNOS is proposed to rely mainly on the haem midpoint
      potential and the ability of the substrate L-Arg to provide a hydrogen bond for
      oxygen activation (O-O scission). We present a study of native iNOS compared with
      iNOS-mesohaem, and investigate the formation of a low-spin ferric haem-aquo or 
      hydroxo species (P) in iNOS mutant W188H substituted with mesohaem. iNOS-mesohaem
      and W188H-mesohaem were stable and dimeric, and presented substrate-binding
      affinities comparable to those of their native counterparts. Single turnover
      reactions catalysed by iNOSoxy with L-Arg (first reaction step) or N-hydroxy-L
      arginine (second reaction step) showed that mesohaem substitution triggered
      higher rates of Fe(II)O2 conversion and altered other key kinetic parameters. We
      elucidated the first crystal structure of a NOS substituted with mesohaem and
      found essentially identical features compared with the structure of iNOS carrying
      native haem. This facilitated the dissection of structural and electronic
      effects. Mesohaem substitution substantially reduced the build-up of species P in
      W188H iNOS during catalysis, thus increasing its proficiency towards NO
      synthesis. The marked structural similarities of iNOSoxy containing native haem
      or mesohaem indicate that the kinetic behaviour observed in mesohaem-substituted
      iNOS is most heavily influenced by electronic effects rather than structural
      alterations.

PMID- 25608849
TI  - Efficacy and safety of a dieckol-rich extract (AG-dieckol) of brown algae,
      Ecklonia cava, in pre-diabetic individuals: a double-blind, randomized, placebo
      controlled clinical trial.
AB  - The effects of 12 weeks of supplementation with a dieckol-rich extract (AG
      dieckol) from brown algae, Ecklonia cava, on glycemic parameters, serum
      biochemistry, and hematology were investigated in this study. Eighty pre-diabetic
      male and female adults were enrolled in a randomized, double-blind, placebo
      controlled trial with parallel-group design. Subjects were randomly allocated
      into two groups designated as placebo and AG-dieckol (1500 mg per day). Compared
      with the placebo group, the AG-dieckol group showed a significant decrease in
      postprandial glucose levels after 12 weeks. The AG-dieckol group also showed a
      significant decrease in insulin and C-peptide levels after 12 weeks, but there
      was no significant difference between the AG-dieckol and placebo groups. There
      were no significant adverse events related to the consumption of AG-dieckol, and
      biochemical and hematological parameters were maintained within the normal range
      during the intervention period. In conclusion, these results demonstrate that AG
      dieckol supplementation significantly contributes to lowering postprandial
      hyperglycemia and in reducing insulin resistance. Furthermore, we believe that
      based on these results the consumption of phlorotannin-rich foods such as marine
      algae may be useful for the treatment of diabetes. 

PMID- 25608850
TI  - ERRATUM: Shaping complex microwave fields in reverberating media with binary
      tunable metasurfaces.

PMID- 25608851
TI  - What do general practitioners think about an online self-regulation programme for
      health promotion? Focus group interviews.
AB  - BACKGROUND: Chronic diseases may be prevented through programmes that promote
      physical activity and healthy nutrition. Computer-tailoring programmes are
      effective in changing behaviour in the short- and long-term. An important issue
      is the implementation of these programmes in general practice. However, there are
      several barriers that hinder the adoption of eHealth programmes in general
      practice. This study explored the feasibility of an eHealth programme that was
      designed, using self-regulation principles. METHODS: Seven focus group interviews
      (a total of 62 GPs) were organized to explore GPs' opinions about the feasibility
      of the eHealth programme for prevention in general practice. At the beginning of
      each focus group, GPs were informed about the principles of the self-regulation
      programme 'My Plan'. Open-ended questions were used to assess the opinion of GPs
      about the content and the use of the programme. The focus groups discussions were
      audio-taped, transcribed and thematically analysed via NVivo software. RESULTS:
      The majority of the GPs was positive about the use of self-regulation strategies
      and about the use of computer-tailored programmes in general practice. There were
      contradictory results about the delivery mode of the programme. GPs also
      indicated that the programme might be less suited for patients with a low
      educational level or for old patients. CONCLUSIONS: Overall, GPs are positive
      about the adoption of self-regulation techniques for health promotion in their
      practice. However, they raised doubts about the adoption in general practice.
      This barrier may be addressed (1) by offering various ways to deliver the
      programme, and (2) by allowing flexibility to match different work flow systems.
      GPs also believed that the acceptability and usability of the programme was low
      for patients who are old or with low education. The issues raised by GPs will
      need to be taken into account when developing and implementing an eHealth
      programme in general practice.

PMID- 25608852
TI  - Synthesis of novel bis-1,5-disubstituted-1H-tetrazoles by an efficient catalyst
      free Ugi-azide repetitive process.
AB  - A series of five novel bis-1,5-disubstituted-1H-tetrazoles (bis-1,5-DS-1H-T) were
      quickly prepared by a catalyst-free Ugi-azide repetitive process from easily
      accessible starting materials in excellent yields, either at room temperature
      (88%-95%) or using mild MW-heating conditions (80%-91%). These molecules may have
      a wide range of applications, such as chelating agents, organocatalysts and
      luminescent materials, and mainly as bioactive compounds. 

PMID- 25608853
TI  - Cross-amplification of Vicia sativa subsp. sativa microsatellites across 22 other
      Vicia species.
AB  - The temperate and herbaceous genus Vicia L. is a member of the legume tribe
      Fabeae of the subfamily Papilionoideae. The genus Vicia comprises 166 annual or
      perennial species distributed mainly in Europe, Asia, and North America, but also
      extending to the temperate regions of South America and tropical Africa. The use
      of simple sequence repeat (SSR) markers for Vicia species has not been
      investigated as extensively as for other crop species. In this study, we assessed
      the potential for cross-species amplification of cDNA microsatellite markers
      developed from common vetch (Vicia sativa subsp. sativa). For cross-species
      amplification of the SSRs, amplification was carried out with genomic DNA
      isolated from two to eight accessions of 22 different Vicia species. For
      individual species or subspecies, the transferability rates ranged from 33% for
      V. ervilia to 82% for V. sativa subsp. nigra with an average rate of 52.0%.
      Because the rate of successful SSR marker amplification generally correlates with
      genetic distance, these SSR markers are potentially useful for analyzing genetic
      relationships between or within Vicia species. 

PMID- 25608854
TI  - Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in SGC-7901
      cells and inhibits tumor growth in vivo.
AB  - Deoxypodophyllotoxin (DPT), a natural microtubule destabilizer, was isolated from
      Anthriscus sylvestris, and a few studies have reported its anti-cancer effect.
      However, the in vivo antitumor efficacy of DPT is currently indeterminate. In
      this study, we investigated the anti-gastric cancer effects of DPT both in vitro
      and in vivo. Our data showed that DPT inhibited cancer cell proliferation and
      induced G2/M cell cycle arrest accompanied by an increase in apoptotic cell death
      in SGC-7901 cancer cells. In addition, DPT caused cyclin B1, Cdc2 and Cdc25C to
      accumulate, decreased the expression of Bcl-2 and activated caspase-3 and PARP,
      suggesting that caspase-mediated pathways were involved in DPT-induced apoptosis.
      Animal studies revealed that DPT significantly inhibited tumor growth and
      decreased microvessel density (MVD) in a xenograft model of gastric cancer. Taken
      together, our findings provide a framework for further exploration of DPT as a
      novel chemotherapeutic for human gastric cancer. 

PMID- 25608855
TI  - Contact toxicity and repellency of the essential oil of Liriope muscari (DECN.)
      bailey against three insect tobacco storage pests.
AB  - In order to find and develop new botanical pesticides against tobacco storage
      pests, bioactivity screening was performed. The essential oil obtained from the
      aerial parts of Liriope muscari was investigated by GC/MS and GC/FID. A total of
      14 components representing 96.12% of the oil were identified and the main
      compounds in the oil were found to be methyl eugenol (42.15%) and safrole
      (17.15%), followed by myristicin (14.18%) and 3,5-dimethoxytoluene (10.60%).
      After screening, the essential oil exhibit potential insecticidal activity. In
      the progress of assay, it showed that the essential oil exhibited potent contact
      toxicity against Tribolium castaneum, Lasioderma serricorne and Liposcelis
      bostrychophila adults, with LD50 values of 13.36, 11.28 ug/adult and 21.37
      ug/cm2, respectively. The essential oil also exhibited strong repellency against
      the three stored product insects. At the same concentrations, the essential oil
      was more repellent to T. castaneum than to L. serricorne adults. The results
      indicate that the essential oil of Liriope muscari has potential to be developed
      into a natural insecticide or repellent for controlling insects in stored tobacco
      and traditional Chinese medicinal materials. 

PMID- 25608856
TI  - Hybrids of salicylalkylamides and Mannich bases: control of the amide
      conformation by hydrogen bonding in solution and in the solid state.
AB  - 3-Aminomethylation of salicylalkylamides afforded hybrids with a Mannich base. In
      addition, it triggered the rotation of the amide bond. The observed
      conformational switch is driven by strong intramolecular hydrogen bonding between
      the Mannich base and phenolic group. Crystal structure analysis reveals the
      stabilization of the hybrid molecules by double hydrogen bonding of the phenolic
      OH, which acts as an acceptor and donor simultaneously. The molecules contain an
      amide site and a Mannich base site in an orthogonal spatial arrangement. The
      intramolecular hydrogen bonds are persistent in a nonpolar solvent (e.g.,
      chloroform). The conformational change can be reversed upon protection or
      protonation of the Mannich base nitrogen. 

PMID- 25608857
TI  - Synthesis and in silico evaluation of novel compounds for PET-based
      investigations of the norepinephrine transporter.
AB  - Since the norepinephrine transporter (NET) is involved in a variety of diseases,
      the investigation of underlying dysregulation-mechanisms of the norepinephrine
      (NE) system is of major interest. Based on the previously described highly potent
      and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro
      2H-benzimidaz- ol-2-one (Me@APPI), this paper aims at the development of several
      fluorinated methylamine-based analogs of this compound. The newly synthesized
      compounds were computationally evaluated for their interactions with the
      monoamine transporters and represent reference compounds for PET-based
      investigation of the NET. 

PMID- 25608858
TI  - Glutathione-garlic sulfur conjugates: slow hydrogen sulfide releasing agents for
      therapeutic applications.
AB  - Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant
      and chemo-sensitization properties, including the in vitro inhibition of tumor
      cell proliferation through the induction of apoptosis. Garlic water- and oil
      soluble allyl sulfur compounds show distinct properties and the capability to
      inhibit the proliferation of tumor cells. In the present study, we optimized a
      new protocol for the extraction of water-soluble compounds from garlic at low
      temperatures and the production of glutathionyl-OSC conjugates during the
      extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in
      vivo metabolism of OSCs and represent active molecules able to affect cellular
      metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione
      conjugates, were here produced and tested for their ability to release hydrogen
      sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide
      sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from
      garlic OSCs and their conjugates has been investigated by molecular in vitro
      experiments. The antiproliferative properties of these extracts on the human T
      cell lymphoma cell line, HuT 78, were observed and related to histone
      hyperacetylation and downregulation of GAPDH expression. Altogether, the results
      presented here pave the way for the production of a GSGaWS as new, slowly
      releasing hydrogen sulfide extract for potential therapeutic applications. 

PMID- 25608859
TI  - Current situation on the availability of nanostructure-biological activity data.
AB  - Recent developments in nanotechnology have not only increased the number of
      nanoproducts on the market, but also raised concerns about the safety of
      engineered nanomaterials (ENMs) for human health and the environment. As the
      production and use of ENMs increase, we are approaching the point at which it is
      impossible to individually assess the toxicity of a vast number of ENMs.
      Therefore, it is desirable to use time-effective computational methods, such as
      the quantitative structure-activity relationship (QSAR) models, to predict the
      toxicity of ENMs. However, the accuracy of the nano-(Q)SARs is directly tied to
      the quality of the data from which the model is estimated. Although the amount of
      available nanotoxicity data is insufficient for generating robust nano-(Q)SAR
      models in most cases, there are a handful of studies that provide appropriate
      experimental data for (Q)SAR-like modelling investigations. The aim of this study
      is to review the available literature data that are particularly suitable for
      nano-(Q)SAR modelling. We hope that this paper can serve as a starting point for
      those who would like to know more about the current availability of experimental
      data on the health effects of ENMs for future modelling purposes. 

PMID- 25608860
TI  - Cerebrovascular and mitochondrial abnormalities in Alzheimer's disease: a brief
      overview.
AB  - Multiple lines of evidence suggest that vascular alterations contribute to
      Alzheimer's disease (AD) pathogenesis. It is also well established that
      mitochondrial abnormalities occur early in course of AD. Here, we give an
      overview of the vascular and mitochondrial abnormalities occurring in AD,
      including mitochondrial alterations in vascular endothelial cells within the
      brain, which is emerging as a common feature that bridges cerebral vasculature
      and mitochondrial metabolism. 

PMID- 25608861
TI  - Beyond the hospital door: a retrospective, cohort study of associations between
      birthing in the public or private sector and women's postpartum care.
AB  - BACKGROUND: In Australia, maternity care is available through universal coverage
      and a parallel, competitive private health insurance system. Differences between
      sectors in antenatal and intrapartum care and associated outcomes are well
      documented but few studies have investigated differences in postpartum care
      following hospital discharge and their impact on maternal satisfaction and
      confidence. METHODS: Women who birthed in Queensland, Australia from February to
      May 2010 were mailed a self-report survey 4 months postpartum. Regression
      analysis was used to determine associations between sector of birth and
      postpartum care, and whether postpartum care experiences explained sector
      differences in postpartum well-being (satisfaction, parenting confidence and
      feeling depressed). RESULTS: Women who birthed in the public sector had higher
      odds of health professional contact in the first 10 days post-discharge and
      satisfaction with the amount of postpartum care. After adjusting for demographic
      and postpartum contact variables, sector of birth no longer had an impact on
      satisfaction (AOR 0.95, 99% CI 0.78-1.31), but any form of health professional
      contact did. Women who had a care provider's 24 hour contact details had higher
      odds of being satisfied (AOR 3.64, 95% CI 3.00-4.42) and confident (AOR 1.34, 95%
      CI 1.08- 1.65). CONCLUSION: Women who birthed in the public sector appeared more
      satisfied because they had higher odds of receiving contact from a health
      professional within 10 days post-discharge. All women should have an opportunity
      to speak to and/or see a doctor, midwife or nurse in the first 10 days at home,
      and the details of a person they can contact 24 hours a day.

PMID- 25608862
TI  - Provision of specific dental procedures by general dentists in the National
      Dental Practice-Based Research Network: questionnaire findings.
AB  - BACKGROUND: Objectives were to: (1) determine whether and how often general
      dentists (GDs) provide specific dental procedures; and (2) test the hypothesis
      that provision is associated with key dentist, practice, and patient
      characteristics. METHODS: GDs (n = 2,367) in the United States National Dental
      Practice-Based Research Network completed an Enrollment Questionnaire that
      included: (1) dentist; (2) practice; and (3) patient characteristics, and how
      commonly they provide each of 10 dental procedures. We determined how commonly
      procedures were provided and tested the hypothesis that provision was
      substantively related to the three sets of characteristics. RESULTS: Two
      procedure categories were classified as "uncommon" (orthodontics, periodontal
      surgery), three were "common" (molar endodontics; implants; non-surgical
      periodontics), and five were "very common" (restorative; esthetic procedures;
      extractions; removable prosthetics; non-molar endodontics). Dentist, practice,
      and patient characteristics were substantively related to procedure provision;
      several characteristics seemed to have pervasive effects, such as dentist gender,
      training after dental school, full-time/part-time status, private practice vs.
      institutional practice, presence of a specialist in the same practice, and
      insurance status of patients. CONCLUSIONS: As a group, GDs provide a
      comprehensive range of procedures. However, provision by individual dentists is
      substantively related to certain dentist, practice, and patient characteristics.
      A large number and broad range of factors seem to influence which procedures GDs
      provide. This may have implications for how GDs respond to the ever-changing
      landscape of dental care utilization, patient population demography, scope of
      practice, delivery models and GDs' evolving role in primary care.

PMID- 25608863
TI  - Cultural variation in emotion perception is real: a response to Sauter, Eisner,
      Ekman, and Scott (2015).

PMID- 25608864
TI  - Emotional vocalizations are recognized across cultures regardless of the valence
      of distractors.

PMID- 25608865
TI  - Asymptomatic myocardial metastasis from cancers of upper aero-digestive tract
      detected on FDG PET/CT: a series of 4 cases.
AB  - Metastatic involvement of the heart is a rare occurrence and remains undiagnosed
      until autopsy. In some instances, patients may have cardiac symptoms, leading to
      ante-mortem diagnosis. Although most primary cancers have been documented to
      metastasize to heart, the existing literature on cancers of upper aero-digestive
      tract is an exception, with only a few reports. We report four cases of upper
      aero-digestive tract cancers, three of which arise from oral cavity, one from
      lower esophagus, metastasising to the myocardium, detected on 18 F - Fluoro-deoxy
      glucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) study , in
      the absence of related symptoms.

PMID- 25608866
TI  - Stigma against HIV/AIDS among female sex workers and general migrant women in
      eastern China.
AB  - BACKGROUND: HIV related stigma is a recognized barrier to early detection of HIV
      and causes great suffering for those affected. However, data regarding HIV
      related stigma among female sex workers (FSW) in China was limited, with none for
      comparison between FSW and general migrant women (GMW). Therefore, the aim of
      this study was to examine HIV related stigma among FSW and GMW in Shanghai,
      China. METHODS: A community based cross-sectional study with face-to-face
      interviews was conducted in Shanghai (September 2011 through December 2012),
      using a structured questionnaire.HIV related stigma scores were examined
      graphically using boxplot. A logistic regression analysis with the proportional
      odds model was employed to identify factors affecting HIV related stigma scores.
      RESULTS: A total of 1,396 subjects, including 721 FSW and 675 GMW, were recruited
      in the present study. Both groups had substantial misconceptions about HIV/AIDS,
      although FSW had slightly higher scores on average. Both groups showed a medium
      level of HIV related stigma (38.34 +/- 6.21 and 38.35 +/- 6.86 for FSW and GMW,
      respectively). For the FSW, higher levels of stigma were observed for those who
      were in the older age groups (age 26-35 years, OR, 2.06, 95% CI 1.06-4.01), those
      who were married (OR, 1.62, 95% CI 1.03-2.54), and those who were working at
      lower-level sex service sites (OR, 1.60, 95% CI 1.06-2.43). Conversely, HIV
      knowledge was inversely associated with the level of HIV related stigma (OR,
      0.93, 95% CI 0.87-0.98).Among GMW participating in the study, those age in the 26
      35 years were more likely to show higher level of stigma (OR, 2.61, 95% CI 1.03
      2.54), and HIV knowledge was found to be inversely associated with the HIV
      related stigma level as well (OR, 0.89, 95% CI 0.84-0.95). CONCLUSIONS: The
      present study suggests that there is an urgent need for the development of
      appropriate education strategies to reduce HIV related stigma among FSW and GMW
      in Shanghai, China. In particular, older women, less educated women, and women
      that have lived in Shanghai a relatively long time should be targeted in future
      stigma reduction programs.

PMID- 25608867
TI  - Assessing cholesterol storage in live cells and C. elegans by stimulated Raman
      scattering imaging of phenyl-Diyne cholesterol.
AB  - We report a cholesterol imaging method using rationally synthesized phenyl-diyne
      cholesterol (PhDY-Chol) and stimulated Raman scattering (SRS) microscope. The
      phenyl-diyne group is biologically inert and provides a Raman scattering cross
      section that is 88 times larger than the endogenous C = O stretching mode. SRS
      microscopy offers an imaging speed that is faster than spontaneous Raman
      microscopy by three orders of magnitude, and a detection sensitivity of 31 MUM
      PhDY-Chol (~1,800 molecules in the excitation volume). Inside living CHO cells,
      PhDY-Chol mimics the behavior of cholesterol, including membrane incorporation
      and esterification. In a cellular model of Niemann-Pick type C disease, PhDY-Chol
      reflects the lysosomal accumulation of cholesterol, and shows relocation to lipid
      droplets after HPbetaCD treatment. In live C. elegans, PhDY-Chol mimics
      cholesterol uptake by intestinal cells and reflects cholesterol storage.
      Together, our work demonstrates an enabling platform for study of cholesterol
      storage and trafficking in living cells and vital organisms. 

PMID- 25608868
TI  - Thyroid hormone responsive protein spot 14 enhances lipogenesis in bovine mammary
      epithelial cells.
AB  - Thyroid hormone responsive spot 14 (THRSP, Spot14, S14) is a nuclear protein that
      regulates milk fat synthesis. To investigate the role of THRSP in lipogenesis in
      the dairy cow mammary gland, first, we examined the association between milk fat
      concentration and THRSP expression in the mammary gland. We found that the dairy
      cow mammary glands that produced milk with high fat had high THRSP mRNA and
      protein levels. Additionally, the study described the consequences of
      overexpression or depletion of THRSP on lipogenesis in cultured bovine mammary
      epithelial cells (BMECs). We found that BMECs with overexpressed THRSP increased
      triacylglycerol levels and enhanced the expression of FAS, PPARgamma, and SREBP1,
      compared with the control BMECs. Depletion of THRSP produced the opposite
      effects. Overall, increased mammary expression of THRSP can be a marker of high
      fat. In addition, our results provide evidence that THRSP may regulate expression
      of PPARgamma and SREBP1 and can regulate milk fat synthesis by directly affecting
      the activity of some classical lipogenic enzymes. 

PMID- 25608869
TI  - engAGE in Community: Using Mixed Methods to Mobilize Older People to Elucidate
      the Age-Friendly Attributes of Urban and Rural Places.
AB  - The growing numbers of older adults in the United States will have a significant
      impact on community resources, which will affect the ability of residents to live
      and thrive in their local community regardless of age. For this study, we applied
      explanatory sequential mixed methods and community-based participatory research
      (CBPR) to discover how attributes of the physical, social, and service
      environments determine residents' perceptions of community age-friendliness and
      conditions for aging-in-place. A population survey measuring county residents' (n
      = 387) perceptions and importance of community resources that support community
      livability are explained by thematic results of the CBPR, that is, emergent
      proximal and distal age-friendly factors. Our qualitative approach engaged local
      people (n = 237) in participatory processes to study and share perceptions of
      environmental attributes in six communities in one Oregon county. Findings are
      integrated to explain similarities and differences in older residents' lived
      experience of rural and urban settings with regard to age-friendly foci.

PMID- 25608870
TI  - A Review of Self-Management Interventions for People With Dementia and Mild
      Cognitive Impairment.
AB  - Self-management offers a way of helping people with dementia or mild cognitive
      impairment (MCI) to play an active role in managing their condition. Barlow,
      Wright, Sheasby, Turner, and Hainsworth have defined self-management as the
      "individual's ability to manage the symptoms, treatment, physical and
      psychosocial consequences and life style changes inherent in living with a
      chronic condition." Although commonly used in other chronic health conditions,
      there has been relatively little exploration of the role of self-management in
      dementia or MCI. This review aimed to identify group-based psychosocial
      interventions for people with dementia or MCI that incorporate significant
      elements of self-management. Fifteen interventions were included in the review:
      12 for people with dementia and 3 for participants with MCI. In both the dementia
      and MCI interventions, the most commonly included self-management components were
      information, communication, and social support, and skills training. The review
      findings indicate that components of self-management have been incorporated into
      group-based interventions for people with dementia and MCI. Further studies are
      needed to address the methodological limitations of the included studies and to
      determine the effectiveness of self-management interventions with these
      populations.

PMID- 25608871
TI  - Evaluation of methods to purify virus-like particles for metagenomic sequencing
      of intestinal viromes.
AB  - BACKGROUND: Viruses are a significant component of the intestinal microbiota in
      mammals. In recent years, advances in sequencing technologies and data analysis
      techniques have enabled detailed metagenomic studies investigating intestinal
      viromes (collections of bacteriophage and eukaryotic viral nucleic acids) and
      their potential contributions to the ecology of the microbiota. An important
      component of virome studies is the isolation and purification of virus-like
      particles (VLPs) from intestinal contents or feces. Several methods have been
      applied to isolate VLPs from intestinal samples, yet to our knowledge, the
      efficiency and reproducibility between methods have not been explored. A rigorous
      evaluation of methods for VLP purification is critical as many studies begin to
      move from descriptive analyses of virus diversity to studies striving to
      quantitatively compare viral abundances across many samples. Therefore,
      reproducible VLP purification methods which allow for high sample throughput are
      needed. Here we compared and evaluated four methods for VLP purification using
      artificial intestinal microbiota samples of known bacterial and viral
      composition. RESULTS: We compared the following four methods of VLP purification
      from fecal samples: (i) filtration + DNase, (ii) dithiothreitol treatment +
      filtration + DNase, (iii) filtration + DNase + PEG precipitation and (iv)
      filtration + DNase + CsCl density gradient centrifugation. Three of the four
      tested methods worked well for VLP purification. We observed several differences
      between methods related to the removal efficiency of bacterial and host DNAs and
      biases against specific phages. In particular the CsCl density gradient
      centrifugation method, which is frequently used for VLP purification, was most
      efficient in removing host derived DNA, but also showed strong discrimination
      against specific phages and showed a lower reproducibility of quantitative
      results. CONCLUSIONS: Based on our data we recommend the use of methods (i) or
      (ii) for large scale studies when quantitative comparison of viral abundances
      across samples is required. The CsCl density gradient centrifugation method,
      while being excellently suited to achieve highly purified samples, in our
      opinion, should be used with caution when performing quantitative studies.

PMID- 25608872
TI  - A lateral electrophoretic flow diagnostic assay.
AB  - Immunochromatographic assays are a cornerstone tool in disease screening. To
      complement existing lateral flow assays (based on wicking flow) we introduce a
      lateral flow format that employs directed electrophoretic transport. The format
      is termed a "lateral e-flow assay" and is designed to support multiplexed
      detection using immobilized reaction volumes of capture antigen. To fabricate the
      lateral e-flow device, we employ mask-based UV photopatterning to selectively
      immobilize unmodified capture antigen along the microchannel in a barcode-like
      pattern. The channel-filling polyacrylamide hydrogel incorporates a photoactive
      moiety (benzophenone) to immobilize capture antigen to the hydrogel without a
      priori antigen modification. We report a heterogeneous sandwich assay using low
      power electrophoresis to drive biospecimen through the capture antigen barcode.
      Fluorescence barcode readout is collected via a low-resource appropriate imaging
      system (CellScope). We characterize lateral e-flow assay performance and
      demonstrate a serum assay for antibodies to the hepatitis C virus (HCV). In a
      pilot study, the lateral e-flow assay positively identifies HCV+ human sera in 60
      min. The lateral e-flow assay provides a flexible format for conducting
      multiplexed immunoassays relevant to confirmatory diagnosis in near-patient
      settings. 

PMID- 25608873
TI  - The bioavailability of the soluble algal products of different microalgal strains
      and its influence on microalgal growth in unsterilized domestic secondary
      effluent.
AB  - Soluble algal products (SAPs) accumulated in microalgal culture could be used as
      carbon source by bacteria, and thus induce serious bacteria contamination. In
      this study, three freshwater microalgal strains, Scenedesmus sp. LX1 (S. LX1),
      Chlorella ellipsoidea YJ1 (C. YJ1) and Haematococcus pluvialis (H. pluvialis),
      were used to investigate the bioavailability of SAPs and its influence on
      microalgal growth in unsterilized domestic secondary effluent. S. LX1 and H.
      pluvialis could grow well whether secondary effluent was sterilized or not, while
      C. YJ1 showed poor growth without sterilization. The assimilable organic carbon
      (AOC) concentration and AOC content in the SAPs of C. YJ1 was as high as 180MUg
      CL(-1) and 3.2%, respectively, which induced more serious bacteria contamination
      and thus inhibited the growth of C. YJ1. Based on the results, in microalgal
      strain selection for massive cultivation, AOC assays of SAPs could be applied to
      examine microalgal susceptibility to bacteria contamination. 

PMID- 25608874
TI  - Tracking down the sources of experimental contamination in microbiome studies.
AB  - A recent report warns that DNA extraction kits and other laboratory reagents are
      considerable sources of contamination in microbiome experiments. The issue of
      contamination is particularly problematic for samples of low biomass. 

PMID- 25608875
TI  - Mapping hotspots of malaria transmission from pre-existing hydrology, geology and
      geomorphology data in the pre-elimination context of Zanzibar, United Republic of
      Tanzania.
AB  - BACKGROUND: Larval source management strategies can play an important role in
      malaria elimination programmes, especially for tackling outdoor biting species
      and for eliminating parasite and vector populations when they are most vulnerable
      during the dry season. Effective larval source management requires tools for
      identifying geographic foci of vector proliferation and malaria transmission
      where these efforts may be concentrated. Previous studies have relied on surface
      topographic wetness to indicate hydrological potential for vector breeding sites,
      but this is unsuitable for karst (limestone) landscapes such as Zanzibar where
      water flow, especially in the dry season, is subterranean and not controlled by
      surface topography. METHODS: We examine the relationship between dry and wet
      season spatial patterns of diagnostic positivity rates of malaria infection
      amongst patients reporting to health facilities on Unguja, Zanzibar, with the
      physical geography of the island, including land cover, elevation, slope angle,
      hydrology, geology and geomorphology in order to identify transmission hot spots
      using Boosted Regression Trees (BRT) analysis. RESULTS: The distribution of both
      wet and dry season malaria infection rates can be predicted using freely
      available static data, such as elevation and geology. Specifically, high
      infection rates in the central and southeast regions of the island coincide with
      outcrops of hard dense limestone which cause locally elevated water tables and
      the location of dolines (shallow depressions plugged with fine-grained material
      promoting the persistence of shallow water bodies). CONCLUSIONS: This analysis
      provides a tractable tool for the identification of malaria hotspots which
      incorporates subterranean hydrology, which can be used to target larval source
      management strategies.

PMID- 25608876
TI  - From concept to content: assessing the implementation fidelity of a chronic care
      model for frail, older people who live at home.
AB  - BACKGROUND: Implementation fidelity, the degree to which a care program is
      implemented as intended, can influence program impact. Since results of trials
      that aim to implement comprehensive care programs for frail, older people have
      been conflicting, assessing implementation fidelity alongside these trials is
      essential to differentiate between flaws inherent to the program and
      implementation issues. This study demonstrates how a theory-based assessment of
      fidelity can increase insight in the implementation process of a complex
      intervention in primary elderly care. METHODS: The Geriatric Care Model was
      implemented among 35 primary care practices in the Netherlands. During home
      visits, practice nurses conducted a comprehensive geriatric assessment and wrote
      a tailored care plan. Multidisciplinary team consultations were organized with
      the aim to enhance the coordination between professionals caring for a single
      patient with complex needs. To assess fidelity, we identified 5 key intervention
      components and formulated corresponding research questions using Carroll's
      framework for fidelity. Adherence (coverage, frequency, duration, content) was
      assessed per intervention component during and at the end of the intervention
      period. Two moderating factors (participant responsiveness and facilitation
      strategies) were assessed at the end of the intervention. RESULTS: Adherence to
      the geriatric assessments and care plans was high, but decreased over time.
      Adherence to multidisciplinary consultations was initially poor, but increased
      over time. We found that individual differences in adherence between practice
      nurses and primary care physicians were moderate, while differences in
      participant responsiveness (satisfaction, involvement) were more distinct. Nurses
      deviated from protocol due to contextual factors and personal work routines.
      CONCLUSIONS: Adherence to the Geriatric Care Model was high for most of the
      essential intervention components. Study limitations include the limited number
      of assessed moderating factors. We argue that a longitudinal investigation of
      adherence per intervention component is essential for a complete understanding of
      the implementation process, but that such investigations may be complicated by
      practical and methodological challenges. TRIAL REGISTRATION: The Netherlands
      National Trial Register (NTR). TRIAL NUMBER: 2160 .

PMID- 25608877
TI  - Effects of peripheral FAAH blockade on NTG-induced hyperalgesia--evaluation of
      URB937 in an animal model of migraine.
AB  - BACKGROUND: Systemic nitroglycerin (NTG) activates brain nuclei involved in
      nociceptive transmission as well as in neuroendocrine and autonomic functions in
      rats. These changes are considered relevant for migraine because NTG consistently
      provokes spontaneous-like migraine attacks in migraineurs. Several studies have
      suggested a relationship between the endocannabinoid levels and pain mediation in
      migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)-the
      enzyme that degrades anandamide, produces analgesia in animal models of pain, but
      there is no information on its effects in migraine. AIM: We evaluated whether
      URB937 alters nociceptive responses in the animal model of migraine based on NTG
      administration in male rats, using the tail flick test and the plantar and
      orofacial formalin tests, under baseline conditions and after NTG administration.
      Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression
      in the brain. RESULTS: During the tail flick test, URB937 showed an
      antinociceptive effect in baseline conditions and it blocked NTG-induced
      hyperalgesia. URB937 also proved effective in counteracting NTG-induced
      hyperalgesia during both the plantar and orofacial formalin tests. Mapping of
      brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos
      expression in the nucleus trigeminalis caudalis and the locus coeruleus.
      CONCLUSIONS: The data suggest that URB937 is capable of changing, probably via
      indirect mechanisms, the functional status of central structures that are
      important for pain transmission in an animal model of migraine.

PMID- 25608878
TI  - Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced
      external carotid vasodilatation in anaesthetised dogs.
AB  - BACKGROUND: During migraine, capsaicin-sensitive trigeminal sensory nerves
      release calcitonin gene-related peptide (CGRP), resulting in cranial
      vasodilatation and central nociception. Moreover, 5-HT is involved in the
      pathophysiology of migraine and depression. Interestingly, some limited lines of
      evidence suggest that fluoxetine may be effective in migraine prophylaxis, but
      the underlying mechanisms are uncertain. Hence, this study investigated the
      canine external carotid vasodilator responses to capsaicin, alpha-CGRP and
      acetylcholine before and after acute and chronic oral treatment with fluoxetine.
      METHODS: Forty-eight vagosympathectomised male mongrel dogs were prepared to
      measure blood pressure, heart rate and external carotid blood flow. The thyroid
      artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal
      cannula was inserted (C1-C3) for infusions of 5-HT. RESULTS: The external carotid
      vasodilator responses to capsaicin, alpha-CGRP and acetylcholine remained
      unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator
      responses to capsaicin, but not those to alpha-CGRP or acetylcholine, were
      inhibited after chronic oral treatment with fluoxetine (300 ug/kg; for 90 days)
      or intrathecal 5-HT. CONCLUSIONS: Chronic oral fluoxetine inhibited capsaicin
      induced external carotid vasodilatation, and this inhibition could partly explain
      its potential prophylactic antimigraine action.

PMID- 25608879
TI  - Primary headache: What's stress got to do with it?

PMID- 25608880
TI  - Not-so-social learning strategies.
AB  - Social learning strategies (SLSs) are rules specifying the conditions in which it
      would be adaptive for animals to copy the behaviour of others rather than to
      persist with a previously established behaviour or to acquire a new behaviour
      through asocial learning. In behavioural ecology, cultural evolutionary theory
      and economics, SLSs are studied using a 'phenotypic gambit'-from a purely
      functional perspective, without reference to their underlying psychological
      mechanisms. However, SLSs are described in these fields as if they were
      implemented by complex, domain-specific, genetically inherited mechanisms of
      decision-making. In this article, we suggest that it is time to begin
      investigating the psychology of SLSs, and we initiate this process by examining
      recent experimental work relating to three groups of strategies: copy when
      alternative unsuccessful, copy when model successful and copy the majority. In
      each case, we argue that the reported behaviour could have been mediated by
      domain-general and taxonomically general psychological mechanisms; specifically,
      by mechanisms, identified through conditioning experiments, that make associative
      learning selective. We also suggest experimental manipulations that could be used
      in future research to resolve more fully the question whether, in non-human
      animals, SLSs are mediated by domain-general or domain-specific psychological
      mechanisms.

PMID- 25608881
TI  - Protein and carbohydrate intake influence sperm number and fertility in male
      cockroaches, but not sperm viability.
AB  - It is commonly assumed that because males produce many, tiny sperm, they are
      cheap to produce. Recent work, however, suggests that sperm production is not
      cost-free. If sperm are costly to produce, sperm number and/or viability should
      be influenced by diet, and this has been documented in numerous species. Yet few
      studies have examined the exact nutrients responsible for mediating these
      effects. Here, we quantify the effects of protein (P) and carbohydrate (C) intake
      on sperm number and viability in the cockroach Nauphoeta cinerea, as well as the
      consequences for male fertility. We found the intake of P and C influenced sperm
      number, being maximized at a high intake of diets with a P : C ratio of 1 : 2,
      but not sperm viability. The nutritional landscapes for male fertility and sperm
      number were closely aligned, suggesting that sperm number is the major
      determinant of male fertility in N. cinerea. Under dietary choice, males regulate
      nutrient intake at a P : C ratio of 1 : 4.95, which is midway between the ratios
      needed to maximize sperm production and pre-copulatory attractiveness in this
      species. This raises the possibility that males regulate nutrient intake to
      balance the trade-off between pre- and post-copulatory traits in this species. 

PMID- 25608882
TI  - Fishing directly selects on growth rate via behaviour: implications of growth
      selection that is independent of size.
AB  - Size-selective harvest of fish and crustacean populations has reduced stock
      numbers, and led to reduced growth rates and earlier maturation. In contrast to
      the focus on size-selective effects of harvest, here, we test the hypothesis that
      fishing may select on life-history traits (here, growth rate) via behaviour, even
      in the absence of size selection. If true, then traditional size-limits used to
      protect segments of a population cannot fully protect fast growers, because at
      any given size, fast-growers will be more vulnerable owing to bolder behaviour.
      We repeatedly measured individual behaviour and growth of 86 crayfish and found
      that fast-growing individuals were consistently bold and voracious over time, and
      were subsequently more likely to be harvested in single- and group-trapping
      trials. In addition, there was some indication that sex had independent effects
      on behaviour and trappability, whereby females tended to be less active, shyer,
      slower-growing and less likely to be harvested, but not all these effects were
      significant. This study represents, to our knowledge, the first across-individual
      support for this hypothesis, and suggests that behaviour is an important
      mechanism for fishing selectivity that could potentially lead to evolution of
      reduced intrinsic growth rates. 

PMID- 25608883
TI  - Genetic and phenotypic changes in an Atlantic salmon population supplemented with
      non-local individuals: a longitudinal study over 21 years.
AB  - While introductions and supplementations using non-native and potentially
      domesticated individuals may have dramatic evolutionary effects on wild
      populations, few studies documented the evolution of genetic diversity and life
      history traits in supplemented populations. Here, we investigated year-to-year
      changes from 1989 to 2009 in genetic admixture at 15 microsatellite loci and in
      phenotypic traits in an Atlantic salmon (Salmo salar) population stocked during
      the first decade of this period with two genetically and phenotypically distinct
      source populations. We detected a pattern of temporally increasing introgressive
      hybridization between the stocked population and both source populations. The
      proportion of fish returning to the river after a single winter at sea (versus
      several ones) was higher in fish assigned to the main source population than in
      local individuals. Moreover, during the first decade of the study, both single
      sea-winter and multi-sea-winter (MSW) fish assigned to the main source population
      were smaller than local fish. During the second decade of the study, MSW fish
      defined as hybrids were lighter and smaller than fish from parental populations,
      suggesting outbreeding depression. Overall, this study suggests that
      supplementation with non-local individuals may alter not only the genetic
      diversity of wild populations but also life-history traits of adaptive
      significance. 

PMID- 25608884
TI  - Top carnivores increase their kill rates on prey as a response to human-induced
      fear.
AB  - The fear induced by predators on their prey is well known to cause behavioural
      adjustments by prey that can ripple through food webs. Little is known, however,
      about the analogous impacts of humans as perceived top predators on the foraging
      behaviour of carnivores. Here, we investigate the influence of human-induced fear
      on puma foraging behaviour using location and prey consumption data from 30
      tagged individuals living along a gradient of human development. We observed
      strong behavioural responses by female pumas to human development, whereby their
      fidelity to kill sites and overall consumption time of prey declined with
      increasing housing density by 36 and 42%, respectively. Females responded to this
      decline in prey consumption time by increasing the number of deer they killed in
      high housing density areas by 36% over what they killed in areas with little
      residential development. The loss of food from declines in prey consumption time
      paired with increases in energetic costs associated with killing more prey may
      have consequences for puma populations, particularly with regard to reproductive
      success. In addition, greater carcass availability is likely to alter community
      dynamics by augmenting food resources for scavengers. In light of the extensive
      and growing impact of habitat modification, our study emphasizes that knowledge
      of the indirect effects of human activity on animal behaviour is a necessary
      component in understanding anthropogenic impacts on community dynamics and food
      web function. 

PMID- 25608885
TI  - Reproductive isolation in a nascent species pair is associated with aneuploidy in
      hybrid offspring.
AB  - Speciation may occur when the genomes of two populations accumulate genetic
      incompatibilities and/or chromosomal rearrangements that prevent inter-breeding
      in nature. Chromosome stability is critical for survival and faithful
      transmission of the genome, and hybridization can compromise this. However, the
      role of chromosomal stability on hybrid incompatibilities has rarely been tested
      in recently diverged populations. Here, we test for chromosomal instability in
      hybrids between nascent species, the 'dwarf' and 'normal' lake whitefish
      (Coregonus clupeaformis). We examined chromosomes in pure embryos, and healthy
      and malformed backcross embryos. While pure individuals displayed chromosome
      numbers corresponding to the expected diploid number (2n = 80), healthy
      backcrosses showed evidence of mitotic instability through an increased variance
      of chromosome numbers within an individual. In malformed backcrosses, extensive
      aneuploidy corresponding to multiples of the haploid number (1n = 40, 2n = 80, 3n
      = 120) was found, suggesting meiotic breakdown in their F1 parent. However, no
      detectable chromosome rearrangements between parental forms were identified.
      Genomic instability through aneuploidy thus appears to contribute to reproductive
      isolation between dwarf and normal lake whitefish, despite their very recent
      divergence (approx. 15-20 000 generations). Our data suggest that genetic
      incompatibilities may accumulate early during speciation and limit hybridization
      between nascent species. 

PMID- 25608886
TI  - Endogenous CCL2 neutralization restricts HIV-1 replication in primary human
      macrophages by inhibiting viral DNA accumulation.
AB  - BACKGROUND: Macrophages are key targets of HIV-1 infection. We have previously
      described that the expression of CC chemokine ligand 2 (CCL2) increases during
      monocyte differentiation to macrophages and it is further up-modulated by HIV-1
      exposure. Moreover, CCL2 acts as an autocrine factor that promotes viral
      replication in infected macrophages. In this study, we dissected the molecular
      mechanisms by which CCL2 neutralization inhibits HIV-1 replication in monocyte
      derived macrophages (MDM), and the potential involvement of the innate
      restriction factors protein sterile alpha motif (SAM) histidine/aspartic acid
      (HD) domain containing 1 (SAMHD1) and apolipoprotein B mRNA-editing, enzyme
      catalytic, polypeptide-like 3 (APOBEC3) family members. RESULTS: CCL2
      neutralization potently reduced the number of p24 Gag+ cells during the course of
      either productive or single cycle infection with HIV-1. In contrast, CCL2
      blocking did not modify entry of HIV-1 based Virus Like Particles, thus
      demonstrating that the restriction involves post-entry steps of the viral life
      cycle. Notably, the accumulation of viral DNA, both total, integrated and 2-LTR
      circles, was strongly impaired by neutralization of CCL2. Looking for correlates
      of HIV-1 DNA accumulation inhibition, we found that the antiviral effect of CCL2
      neutralization was independent of the modulation of SAMHD1 expression or
      function. Conversely, a strong and selective induction of APOBEC3A expression, to
      levels comparable to those of freshly isolated monocytes, was associated with the
      inhibition of HIV-1 replication mediated by CCL2 blocking. Interestingly, the
      CCL2 neutralization mediated increase of APOBEC3A expression was type I IFN
      independent. Moreover, the transcriptome analysis of the effect of CCL2 blocking
      on global gene expression revealed that the neutralization of this chemokine
      resulted in the upmodulation of additional genes involved in the defence response
      to viruses. CONCLUSIONS: Neutralization of endogenous CCL2 determines a profound
      restriction of HIV-1 replication in primary MDM affecting post-entry steps of the
      viral life cycle with a mechanism independent of SAMHD1. In addition, CCL2
      blocking is associated with induction of APOBEC3A expression, thus unravelling a
      novel mechanism which might contribute to regulate the expression of innate
      intracellular viral antagonists in vivo. Thus, our study may potentially lead to
      the development of new therapeutic strategies for enhancing innate cellular
      defences against HIV-1 and protecting macrophages from infection.

PMID- 25608888
TI  - A neuroprosthesis for control of seated balance after spinal cord injury.
AB  - BACKGROUND: A major desire of individuals with spinal cord injury (SCI) is the
      ability to maintain a stable trunk while in a seated position. Such stability is
      invaluable during many activities of daily living (ADL) such as regular work in
      the home and office environments, wheelchair propulsion and driving a vehicle.
      Functional neuromuscular stimulation (FNS) has the ability to restore function to
      paralyzed muscles by application of measured low-level currents to the nerves
      serving those muscles. METHODS: A feedback control system for maintaining seated
      balance under external perturbations was designed and tested in individuals with
      thoracic and cervical level spinal cord injuries. The control system relied on a
      signal related to the tilt of the trunk from the vertical position (which varied
      between 1.0 = erect posture and 0.0 = most forward flexed posture) derived from a
      sensor fixed to the sternum to activate the user's own hip and trunk extensor
      muscles via an implanted neuroprosthesis. A proportional-derivative controller
      modulated stimulation between trunk tilt values indicating deviation from the
      erect posture and maximum desired forward flexion. Tests were carried out with
      external perturbation forces set at 35%, 40% and 45% body-weight (BW) and maximal
      forward trunk tilt flexion thresholds set at 0.85, 0.75 and 0.70. RESULTS:
      Preliminary tests in a case series of five subjects show that the controller
      could maintain trunk stability in the sagittal plane for perturbations up to 45%
      of body weight and for flexion thresholds as low as 0.7. The mean settling time
      varied across subjects from 0.5(+/-0.4) and 2.0 (+/-1.1) seconds. Mean response
      time of the feedback control system varied from 393(+/-38) ms and 536(+/-84) ms
      across the cohort. CONCLUSIONS: The results show the high potential for robust
      control of seated balance against nominal perturbations in individuals with
      spinal cord injury and indicates that trunk control with FNS is a promising
      intervention for individuals with SCI.

PMID- 25608887
TI  - New targeted molecular therapies for cancer: radiological response in
      intrathoracic malignancies and cardiopulmonary toxicity: what the radiologist
      needs to know.
AB  - The emergence of new novel therapeutic agents which directly target molecules
      that are uniquely or abnormally expressed in cancer cells (molecular targeted
      therapy, MTT) has changed dramatically the treatment of cancer in recent years.
      The clinical benefit associated with these agents is typically limited to a
      subset of treated patients, who in many cases are defined by a specific genomic
      mutations and expression lesion within their tumor cells. All these new therapy
      modalities represent new challenges to radiologists as their mechanism of action
      and side effect profiles differ from conventional chemotherapy agents. In this
      article we will discuss radiological patterns of response to molecular targeted
      therapies MTT in lung cancer, typical and atypical radiological responses of
      targeted molecular therapy for other intra thoracic malignancies, cardiopulmonary
      toxicity and other side effects of molecular targeted therapy MTT in the thorax. 

PMID- 25608889
TI  - Quantifying the demand for hospital care services: a time and motion study.
AB  - BACKGROUND: The actual amount of care hospitalised patients need is unclear. A
      model to quantify the demand for hospital care services among various clinical
      specialties would avail healthcare professionals and managers to anticipate the
      demand and costs for clinical care. METHODS: Three medical specialties in a Dutch
      university hospital participated in this prospective time and motion study. To
      include a representative sample of patients admitted to clinical wards, the most
      common admission diagnoses were selected from the most recent update of the
      national medical registry (LMR) of ICD-10 admission diagnoses. The investigators
      recorded the time spent by physicians and nurses on patient care. Also the costs
      involved in medical and nursing care, (surgical) interventions, and diagnostic
      procedures as an estimate of the demand for hospital care services per
      hospitalised patient were calculated and cumulated. Linear regression analysis
      was applied to determine significant factors including patient and healthcare
      outcome characteristics. RESULTS: Fifty patients on the Surgery (19), Pediatrics
      (17), and Obstetrics & Gynecology (14) wards were monitored during their
      hospitalization. Characteristics significantly associated with the demand for
      healthcare were: polypharmacy during hospitalization, complication severity
      level, and whether a surgical intervention was performed. CONCLUSIONS: A set of
      predictors of the demand for hospital care services was found applicable to
      different clinical specialties. These factors can all be identified during
      hospitalization and be used as a managerial tool to monitor the patients' demand
      for hospital care services and to detect trends in time.

PMID- 25608891
TI  - [Involvement of cellular immunity and humoral immunity in mixed allergy induced
      by trichloroethylene].
AB  - OBJECTIVE: To investigate whether cellular immunity and humoral immunity are
      involved in trichlorethylene (TCE)-induced mixed allergy, then provide the
      scientific basis for the mechanism of this disease. METHODS: Guinea pigs and rats
      were tested for this study by application of guinea pig maximization test (GPMT),
      the animals were randomly divided into negative control, positive control and TCE
      treatment groups. Animals of these groups were administrated with olive oil, 2, 4
      dinitrochlorobenzene (DNCB), and TCE, respectively, by intradermal injection.
      After TCE administration, rat peripheral blood samples were collected by flow
      cytometry to detect lymphocytes CD3+, CD4+, CD8+. Guinea pig peripheral blood
      samples were collected to detect the levels of IgG, IgA, IgM, C3, C4, and the
      spleens were taken out from guinea pigs after various treatment, mRNA expression
      of GATA3, T-bet, CTLA4 and Foxp3 in lymphocytes of guinea pig spleen was detected
      by real-time fluorescent PCR assay. Additionally, TCE allergic dermatitis
      patients were selected for the study, the peripheral blood samples were collected
      from the TCE patients group and control group, quantitative PCR was applied to
      detect mRNA expression of immune-related genes Foxp3, GATA3, CTLA4, T-bet.
      RESULTS: TCE induced obvious skin allergic reaction in guinea pigs, the
      sensitization rate was 83.3%, IgG levels in TCE group and positive control
      increased significantly. Additionally, mRNA expression levels of GATA3, T-bet,
      CTLA4 significantly elevated in TCE group and positive control, but Foxp3 mRNA
      levels decreased. The lymphocytes CD3+ ratio in TCE group and positive control of
      rats was higher than that in negative control, we found that there was no
      statistical difference of CD4+, CD8+, CD4+/CD8+ between TCE group and negative
      control of rats. The mRNA expression levels of Foxp3, GATA3, CTLA4 in TCE
      patients increased by 115%, 97%, 241%, respectively as compared with the control,
      T-bet levels decreased by 47%when compared with the control. CONCLUSIONS: TCE
      could induce obvious changes of cellular immunity and humoral immunity in guinea
      pigs, rats, and TCE patients, these findings indicated that TCE-induced
      immunological disorder belongs to the mixed allergy with involvment of cellular
      immunity and humoral immunity, the mixed allergy might be type IV and type II
      allergy.

PMID- 25608890
TI  - Differential expression of alpha-L-arabinofuranosidases during maize (Zea mays
      L.) root elongation.
AB  - MAIN CONCLUSION: Specific alpha- l -arabinofuranosidases are involved in the
      realisation of elongation growth process in cells with type II cell walls.
      Elongation growth in a plant cell is largely based on modification of the cell
      wall. In type II cell walls, the Ara/Xyl ratio is known to decrease during
      elongation due to the partial removal of Ara residues from glucuronoarabinoxylan.
      We searched within the maize genome for the genes of all predicted alpha-L
      arabinofuranosidases that may be responsible for such a process and related their
      expression to the activity of the enzyme and the amount of free arabinose
      measured in six zones of a growing maize root. Eight genes of the GH51 family
      (ZmaABFs) and one gene of the GH3 family (ZmaARA-I) were identified. The
      abundance of ZmaABF1 and 3-6 transcripts was highly correlated with the measured
      enzymatic activity and free arabinose content that significantly increased during
      elongation. The transcript abundances also coincided with the pattern of changes
      in the Ara/Xyl ratio of the xylanase-extractable glucuronoarabinoxylan described
      in previous studies. The expression of ZmaABF3, 5 and 6 was especially up
      regulated during elongation although corresponding proteins are devoid of the
      catalytic glutamate at the proper position. ZmaABF2 transcripts were specifically
      enriched in the root cap and meristem. A single ZmaARA-I gene was not expressed
      as a whole gene but instead as splice variants that encode the C-terminal end of
      the protein. Changes in the ZmaARA-I transcript level were rather moderate and
      had no significant correlation with free arabinose content. Thus, elongation
      growth of cells with type II cell walls is accompanied by the up-regulation of
      specific and predicted alpha-L-arabinofuranosidase genes, and the corresponding
      activity is indeed pronounced and is important for the modification of
      glucuronoarabinoxylan, which plays a key role in the modification of the cell
      wall supramolecular organisation.

PMID- 25608892
TI  - [Early changes in renal injury parameters and their influencing factors in
      workers exposed to mercury].
AB  - OBJECTIVE: To investigate atmospheric mercury concentration in the workplace and
      urinary mercury concentration in workers exposed to mercury in a thermometer
      factory, and to determine the levels and influencing factors of urinary Beta2
      microglobulin (Beta2-MG) and retinol-binding protein (RBP) in these workers.
      METHODS: An occupational health survey of the workplace was completed according
      to relevant national occupational health standards. Questionnaire survey and
      occupational health examination were conducted in 178 workers exposed to mercury
      in the factory. Statistical analysis was accomplished using SPSS 19.0. RESULTS:
      In the workplace, atmospheric mercury concentration was out of limits at seven of
      eight detection points expressed by short-term exposure limit; it was out of
      limits at all the eight detection points shown by time-weighted average.
      Statistically significant difference in atmospheric mercury concentration was
      found among different detection points (F = 138.714, P < 0.001). The geometric
      mean of urinary mercury concentration measured in 154 workers was 171.607 ug/g.
      There were 127 workers with urinary mercury concentration exceeding the standard
      (82.5% over-standard rate). Significant difference in urinary mercury
      concentration was shown in the workers among different positions (chi2 = 44.531,
      P < 0.01). Urinary mercury concentration was positively correlated with
      atmospheric mercury concentration (r = 0.624, P < 0.01). The mean urinary Beta2
      MG level measured in 148 workers was 0.142 mg/L, and seven workers had urinary
      Beta2-MG levels greater than 0.3 mg/L (4.7% abnormal rate). The mean urinary RBP
      level measured in 153 workers was 0.485 mg/L, and 19 workers had urinary RBP
      levels greater than 0.7 mg/L (12.4% abnormal rate). Ordinal logistic regression
      showed that age >34 years (OR = 4.88, 95%CI: 2.24~10.62) and length of service
      >15 years (OR = 2.50, 95%CI: 1.06-5.92) were risk factors for increased urinary
      Beta2-MG level. Age >45 years (OR = 7.52, 95%CI: 2.50~22.65) was a risk factor
      for increased urinary RBP level. CONCLUSION: In the thermometer factory under
      study, atmospheric and urinary mercury concentrations both seriously exceeded the
      standards, which were harmful to the health of workers. High atmospheric mercury
      concentration, old age, and long length of service were risk factors for
      increased urinary Beta2-MG and RBP levels in workers exposed to mercury.

PMID- 25608893
TI  - [The coverage of work injury insurance and its affecting factors in Zhejiang
      province, China].
AB  - OBJECTIVE: In China, the coverage rate of work injury insurance was 23.2%in 2011,
      which was far lower than expected. The factors affecting the insurance's
      enrollment has very little known. This paper aims to study the existing coverage
      of work injury insurance scheme and its influencing factors. METHODS: The data
      were collected from 2 836 workers who came from 9 industries in three cities of
      Zhejiang province using face-to-face questionnaire interview. RESULTS: Of these
      2836 workers, the work injury insurance coverage was 50.1%, and 29.6% were not
      sure if they were covered or not. The results showed that the awareness of
      occupational disease and industrial injury insurance was helpful in increasing
      the coverage rate. Besides, the logistic regression analysis showed that in
      certain circumstances working population shared higher coverage of work injury
      insurance. For examples, male workers with local household registration and
      longer working years; people who had been informed about occupational risk
      factors, and thus gained more training on the issue; people who had exposed to
      occupational hazards or involved in administrative duties; and people who had
      already insured by a medical insurance scheme. In the contrary, the heavier
      family burden with longer working hours per week they needed, the lower
      possibility they joined the insurance scheme. CONCLUSIONS: The coverage of work
      injury insurance is higher than native average level but much lower than the
      average international level. The awareness of occupational disease and injury
      insurance was closely associated with the coverage of work injury insurance.
      Therefore, it is imperative to popularize the knowledge on OHS for migrant
      workers, as well as to reinforce the supervision and management of the issue
      would have been an effective way to elevate the coverage rate of work injury
      insurance.

PMID- 25608894
TI  - [A comparative analysis of health promotion demand in practitioners between urban
      and rural private enterprises].
AB  - OBJECTIVE: To assess the differences in the health promotion demand of
      practitioners between urban and rural private enterprises by a comparative
      analysis, and to probe into the more scientific and targeted health promotion
      measures. METHODS: Stratified cluster random sampling and self-designed
      questionnaire were adopted to survey 852 practitioners in urban and rural private
      enterprises of a Chinese city. RESULTS: There were significant differences in
      practitioners between the two sorts of enterprises in terms of age, length of
      service, educational level, and forms of employment (P < 0.05 or P < 0.01). The
      basic knowledge and skills of practitioners in rural private enterprises were
      worse than those in urban private enterprises(P < 0.05 or P < 0.01).
      Practitioners in rural private enterprises were significantly less inclined to
      gain basic health promotion knowledge through enterprise training and network(P <
      0.01). The demand of practitioners for health examination and hazard notification
      was significantly lower in rural private enterprises than in urban private
      enterprises (P < 0.05). CONCLUSION: Focused and targeted health promotion should
      be carried out based on different demand characteristics of practitioners in
      rural and urban private enterprises.

PMID- 25608895
TI  - [Analysis of authors in Chinese Journal of Industrial Hygiene and Occupational
      Diseases from 2006 to 2013].
AB  - OBJECTIVE: To investigate the distribution of authors, funding, institutions, and
      regions in Chinese Journal of Industrial Hygiene and Occupational Diseases
      between 2006 and 2013, to understand the types and characteristics of
      cooperation, and to identify the core authors, core institutions, and core
      regions. METHODS: Based on the Chinese Science Citation Database, the data on the
      journal were analyzed by bibliometric methods, including the number of papers,
      cooperation, core authors, regional distribution of authors, systematic
      distribution of authors, productive institutions, and funding sources and
      distribution. RESULTS: Within the eight years, there were 2488 papers published
      in the journal, and 1363 authors published only one paper in the journal,
      accounting for 76.57%of the number of first authors. A total of 2304 (92.60%) out
      of 2488 papers were published by co-authors and the degree of cooperation was
      4.64. One hundred and eighty-four papers (7.40%) were published by only one
      author. There were 64 (3.60%) core authors who published 324 papers (13.02%).
      Nine hundred and sixty-eight papers (38.91%) were published by research
      institutes, 825 papers (33.16%) by universities, and 272 papers (10.93%) by
      affiliated hospitals of medical universities. There were 19 productive
      institutions publishing 838 papers (33.68%), in which Beijing ranked first with
      300 papers (12.06%). CONCLUSION: The journal has a large number of authors,
      extensive institutions, a wide regional distribution, a high cooperation rate,
      and a strong ability to attract funded papers. Research institutes and
      universities are the main sources of papers in the journal.

PMID- 25608896
TI  - [Impact of combined effect of noise and heat on blood pressure: a meta-analysis].

PMID- 25608897
TI  - [The medical staff of blood-occupational exposure investigation and intervention
      analysis in a hospital from 2009 to 2013].

PMID- 25608898
TI  - [Effects of nanosized cadmium sulfide on male reproductive system in mice].
AB  - OBJECTIVE: To investigate the effects of nanosized cadmium sulfide (nano-CdS) on
      the male reproductive system in mice. METHODS: Thirty-six specific pathogen?free
      male ICR mice were equally and randomly divided into three groups: two
      experimental groups and a control group. The two experimental groups were exposed
      to 100 mg/kg and 50 mg/kg nano-CdS once daily by gavage, respectively, while the
      control group was exposed to the same volume of physiological saline once daily
      by gavage. After 45 days, levels of cadmium accumulation and serum testosterone
      in the testis were determined, the epididymal sperm count, the rate of sperm
      abnormality, and histopathological changes in testis tissue were observed under a
      microscope, and the level of CYP11A1 mRNA was determined by qRT-PCR. RESULTS:
      Compared with the control group, the two experimental groups had a significantly
      increased level of cadmium accumulation in the testis (P < 0.05), and the 100
      mg/kg nano-CdS group had a significantly decreased epididymal sperm count (P <
      0.05) and a significantly increased rate of sperm abnormality (P < 0.05), but the
      50 mg/kg nano-CdS group did not. The 100 mg/kg nano-CdS group showed different
      histopathological changes in testis tissue, but the 50 mg/kg nano-CdS group did
      not. The two experimental groups had significantly reduced levels of testosterone
      and CYP11A1 mRNA compared with the control group. CONCLUSION: Nano-CdS given
      through the digestive tract may have an effect on the male reproductive system in
      mice by affecting the key enzyme genes in the androgen synthesis pathway to
      reduce the levels of reproductive hormones.

PMID- 25608899
TI  - [Clinical efficacy of mouse nerve growth factor in treatment of occupational hand
      arm vibration disease].
AB  - OBJECTIVE: To investigate the efficacy of mouse nerve growth factor (mNGF) in
      treating occupational hand-arm vibration disease (HAVD). METHODS: Sixty-four
      patients with HAVD were equally and randomly divided into treatment group and
      control group. The control group was given Salvia miltiorrhiza Bunge and
      deproteinized extract of calf blood to improve circulation, and also given
      methylcobalamin tablets and vitamin B6 for neurotrophic treatment. In addition to
      the above treatments for the control group, the treatment group was also given 30
      ug/d mNGF by intramuscular injection for two courses (4 weeks for each course)
      with a 15-day interval. RESULTS: Both the treatment group and the control group
      showed significant improvements in clinical symptoms and signs (hand numbness and
      pain, and reduced senses of touch, pain, and vibration), cold water loading test
      (CWLT), and electroneuromyography (ENMG) after treatments (P < 0.05). And the
      treatment group had significantly more improvements than the control group (P <
      0.05). CONCLUSION: mNGF can significantly improve hand numbness and pain, reduced
      senses of touch, pain, and vibration, CWLT, and ENMG, so it has better clinical
      effect and safety in treating HAVD. Early diagnosis and treatment can improve the
      outcome of patients with HAVD.

PMID- 25608900
TI  - [Clinical effect of hemoperfusion combined with hemodialysis in treatment of
      severe organophosphate pesticide poisoning].
AB  - OBJECTIVE: To investigate the clinical effect of hemoperfusion combined with
      hemodialysis in the treatment of severe organophosphate pesticide poisoning.
      METHODS: Ninety-eight patients with severe organophosphate pesticide poisoning
      who were admitted to the emergency department of our hospital from March 2005 to
      September 2013 were equally divided into control group and observation group
      according to treatment methods. The control group was given conventional
      emergency treatment, while the observation group was given hemoperfusion combined
      with hemodialysis and the conventional emergency treatment. The clinical outcomes
      and complications of two groups were compared. RESULTS: In the control group, 35
      patients were cured and 14 patients died, so the cure rate was 71.4%. In the
      treatment group, 46 patients were cured and 3 patients died, so the cure rate was
      93.9%. The treatment group had a significantly higher cure rate than the control
      group (chi2 = 8.611, P < 0.05). And the treatment group had significantly shorter
      duration of coma (P < 0.01), mean length of hospital stay (P < 0.01), and time to
      recovery of cholinesterase activity (P < 0.01) and a significantly reduced dose
      of atropine than the control group (P < 0.01). The control group had
      significantly more cases of urinary retention than the treatment group (18 vs. 6,
      chi2 = 4.991, P < 0.05). And the control group had more cases of intermediate
      syndrome, respiratory failure, delayed neurological damage, and rebound than the
      treatment group. CONCLUSION: Hemoperfusion combined hemodialysis has a good
      clinical effect and causes fewer complications in treating severe organophosphate
      pesticide poisoning, so it is worthy of clinical promotion.

PMID- 25608901
TI  - [Misdiagnosis of occupational chronic n-hexane poisoning: an analysis of 16
      cases].
AB  - OBJECTIVE: To analyze the cause of misdiagnosis of occupational chronic n-hexane
      poisoning and to investigate the diagnosis and differential diagnosis of this
      disease. METHODS: The clinical data of 16 patients with occupational chronic n
      hexane poisoning who had been misdiagnosed with other diseases were collected.
      The hospital they first visited, cause of misdiagnosis, clinical features, and
      the misdiagnosis rate among inpatients during the same period were
      retrospectively analyzed. RESULTS: Sixteen of 62 patients hospitalized during the
      same period were misdiagnosed at the first visit; 11 cases were in the upper
      first-class hospitals, and 5 cases in the upper second-class hospitals; 5 cases
      were misdiagnosed as Green Barry syndrome, 2 cases as motor neuron disease, 2
      cases as drug-induced peripheral neuropathy, 3 cases as periodic paralysis, and 4
      cases had uncertain diagnosis. CONCLUSION: Most doctors who work in ordinary
      hospitals do not know occupational chronic n-hexane poisoning, which is often
      misdiagnosed as general neuropathies or difficult diseases. The key to correct
      diagnosis is to know the patient's occupational history and clinical features.

PMID- 25608902
TI  - [Study on tissue Doppler imaging in diagnosis of right ventricular hypertrophy in
      patients with silicosis complicated by chronic pulmonary heart disease].
AB  - OBJECTIVE: To investigate the value of tissue Doppler imaging (TDI) in the
      diagnosis of right ventricular hypertrophy in patients with silicosis complicated
      by chronic pulmonary heart disease. METHODS: A total of 50 cases of silicosis
      complicated by chronic pulmonary heart disease in our hospital underwent
      conventional electrocardiography (ECG) and TDI. The detection rates for right
      ventricular hypertrophy by two methods were compared. RESULTS: Of 50 cases of
      silicosis complicated by chronic pulmonary heart disease, 19 were diagnosed with
      right ventricular hypertrophy by ECG, with a detection rate of 38.0%; 29 were
      diagnosed with right ventricular hypertrophy by TDI, with a detection rate off
      58.0%. Statistical analysis suggested that TDI leads to a significantly higher
      detection rate for right ventricular hypertrophy in patients with silicosis
      complicated by chronic pulmonary heart disease (chi2 = 4.006, P = 0.036).
      CONCLUSION: Both TDI and ECG can be used for detecting right ventricular
      hypertrophy in patients with silicosis complicated by chronic pulmonary heart
      disease, but the detection rate is higher when TDI is employed. In addition, ECG
      cannot directly reflect the increase in pulmonary artery pressure. Therefore, TDI
      is more suitable for the diagnosis of right ventricular hypertrophy in patients
      with silicosis complicated by chronic pulmonary heart disease and provides a
      strong diagnostic basis for the clinical treatment of silicosis complicated by
      pulmonary heart disease.

PMID- 25608904
TI  - [Advances in exposome and exposomics].

PMID- 25608903
TI  - [Study on the method for determination of glyphosate in workplace air by HPLC
      post-column derivatization].

PMID- 25608906
TI  - [Investigation progress of the hazard and prevention of infections diseases in
      medical workers].

PMID- 25608905
TI  - [Review of biomarkers of exposure of Indium and its compounds].

PMID- 25608907
TI  - [Review of investigation in 1-bromopropane poisoning].

PMID- 25608908
TI  - [Comparative study on standards for hand-transmitted vibration of measurement and
      evaluation at home and abroad].

PMID- 25608910
TI  - Chromogenic assays for measurement of rivaroxaban from EDTA anticoagulated plasma
      samples.

PMID- 25608911
TI  - A rare complication of reduction malarplasty.
AB  - In this report, the authors introduce a rare complication after reduction
      malarplasty in a 21-year-old male patient. The patient underwent two-jaw surgery
      and reduction malarplasty at a local plastic surgery clinic in December 2012. He
      presented with mass-like swelling of the left temporomandibular joint (TMJ) and a
      clicking sound with jaw movement that began 5 months after surgery. Physical
      examination, ultrasonography, and enhanced facial 3-dimensional computed
      tomography indicated suspicion of TMJ capsule injury. Therefore, mass excisional
      biopsy was performed with plate and screw removal. Biopsy results of the excised
      cystic mass revealed bursitis. The patient's symptoms disappeared after surgery.
      This is the first report of bursitis as a rare complication after reduction
      malarplasty. 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- 25608912
TI  - Red breast syndrome: a review of available literature.
AB  - There is scant literature regarding a recently identified clinical entity termed
      red breast syndrome. Its clinical presentation has been described as a non
      infectious, self-limited erythema of a post-mastectomy breast reconstructed using
      acellular dermal matrix. Its incidence, risk factors, pathophysiology, clinical
      course, management, and long-term sequelae are largely unknown. We present a
      review of the available literature on this phenomenon and highlight some
      opportunities for further research. 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- 25608913
TI  - Measurement of Head Impact Due to Standing Fall in Adults Using Anthropomorphic
      Test Dummies.
AB  - The kinematics and kinetics of head impact due to a standing fall onto a hard
      surface are summarized. Head injury due to impact from falls represents a
      significant problem, especially for older individuals. When the head is left
      unprotected during a fall, the impact severity can be high enough to cause
      significant injury or even death. To ascertain the range of head impact
      parameters, the dynamic response was captured for the pedestrian version of the
      5th percentile female and 50th percentile male Hybrid III anthropomorphic test
      dummies as they were dropped from a standing position with different initial
      postures. Five scenarios of falls were considered including backward falls
      with/without hip flexion, forward falls with/without knee flexion and lateral
      falls. The results show that the head impact parameters are dependent on the fall
      scenario. A wide range of impact parameters was observed in 107 trials. The 95%
      prediction interval for the peak translational acceleration, peak angular
      acceleration, peak force, impact translational velocity and peak angular velocity
      are 146-502 g, 8.8-43.3 krad/s(2), 3.9-24.5 kN, 2.02-7.41 m/s, and 12.9-70.3
      rad/s, respectively.

PMID- 25608914
TI  - [Prophylactic antibiotic use in ENT surgery].
AB  - Surgical antibiotic prophylaxis (SAP) is defined as the administration of an
      antimicrobial agent prior to contamination in previously sterile spaces and
      fluid. SAP should not be confused with the therapeutic use of antibiotics. There
      are a growing number of studies with the goal of answering the question which
      patients benefit most from SAP during which specific surgical procedure. However,
      in the specific surgical field of head and neck surgery and otolaryngological
      surgery, there are only a few guidelines answering that question for specific
      procedures. The aim of this study was to analyze the evidence found in the
      literature and to develop a standard operating procedure, which specifically
      addresses head and neck and otolaryngeal surgical procedures. 

PMID- 25608915
TI  - Quality of life and factors predictive of burden among primary caregivers of
      chronic liver disease patients.
AB  - BACKGROUND: Chronic liver disease increases the socioeconomic and emotional
      burden on the patient's caregiver. This is important because a patient's
      adherence to therapy and transplant eligibility is dependent on the caregiver's
      ability to handle these challenges. METHODS: This was a prospective, cross
      sectional study of 50 primary caregivers of patients with advanced liver disease.
      Caregivers completed the RAND 36-item (Short Form [SF-36]) Health Survey and the
      Zarit Burden Scale survey. Caregiver quality of life, based on the SF-36, was
      compared using t-tests with the scores of the National reference population as
      controls. RESULTS: In our cohort, the mean age of caregivers was 56.9+/-11.4
      years, 40 (83.3%) were female, and 34 (70.8%) were spouses/significant others of
      the patient. Compared with the adjusted National norm data, caregivers scored
      substantially lower in categories of role limitations due to emotional problems
      (P<0.001), vitality (P=0.025), mental health (P=0.005), and social functioning
      (P=0.002). While the adjusted physical component score of the caregivers was
      comparable to the National mean, the mental component score (MCS) was lower than
      the National average (42.4+/-13.3 vs. 50.0+/-10, P<0.001). Though only 8 of 50
      (16.0%) subjects reported a formal diagnosis of depression or anxiety, 23 (46.0%)
      had MCS <42, a strong predictor of clinical depression, based on previous
      studies. CONCLUSIONS: Primary caregivers of patients with advanced liver disease
      have significantly lower SF-36 mental health scores compared with the general
      population. Comparison of SF-36 scores to caregiver history suggests under
      recognition of mental health problems in this population.

PMID- 25608916
TI  - The International Multidisciplinary Consensus Conference on Multimodality
      Monitoring in Neurocritical Care: evidentiary tables: a statement for healthcare
      professionals from the Neurocritical Care Society and the European Society of
      Intensive Care Medicine.
AB  - A variety of technologies have been developed to assist decision-making during
      the management of patients with acute brain injury who require intensive care. A
      large body of research has been generated describing these various technologies.
      The Neurocritical Care Society (NCS) in collaboration with the European Society
      of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine
      (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an
      international, multidisciplinary consensus conference to perform a systematic
      review of the published literature to help develop evidence-based practice
      recommendations on bedside physiologic monitoring. This supplement contains a
      Consensus Summary Statement with recommendations and individual topic reviews on
      physiologic processes important in the care of acute brain injury. In this
      article we provide the evidentiary tables for select topics including systemic
      hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain
      metabolism, biomarkers, processes of care and monitoring in emerging economies to
      provide the clinician ready access to evidence that supports recommendations
      about neuromonitoring. 

PMID- 25608917
TI  - An exploratory study; the therapeutic effects of premixed activated charcoal
      sorbitol administration in patients poisoned with organophosphate pesticide.
AB  - OBJECTIVE: The effects of activated charcoal (AC) mixed with cathartics for
      gastric decontamination in the management of organophosphate (OP) poisoning
      remain unknown due to limited clinical evidence. This exploratory study assessed
      the effectiveness of premixed AC-sorbitol as a treatment for OP poisoning.
      MATERIALS AND METHODS: This retrospective observational case study included
      patients who either did not receive AC-sorbitol or received a single dose of AC
      sorbitol within 24 h after OP ingestion. The patients were divided into three
      groups: no AC-sorbitol treatment, patients who received AC-sorbitol within 1 h of
      OP ingestion, and patients who received AC-sorbitol more than 1 h after OP
      ingestion. Mortality, the development of respiratory failure, and the duration of
      mechanical ventilation were used as outcome measurements for effectiveness,
      whereas aspiration pneumonia and electrolyte imbalance were employed as safety
      measurements. RESULT: Among 262 patients with OP poisoning, 198 were included. Of
      these, 133 patients did not receive AC-sorbitol, whereas 14 and 51 patients
      received AC-sorbitol within 1 h or more than 1 h after ingestion, respectively.
      The time from ingestion to hospital arrival and time from ingestion to
      administration of atropine and pralidoxime differed among the groups, whereas
      other characteristics, including age, amount ingested, and type of ingested OP,
      were similar among the groups. Univariate and multivariate analysis demonstrated
      that the administration of AC-sorbitol was not associated with outcome measures
      for effectiveness and did not significantly increase either aspiration pneumonia
      or electrolyte imbalances during hospitalization. DISCUSSION AND CONCLUSION: The
      administration of AC-sorbitol exerted neither beneficial nor harmful effects on
      the outcomes of OP-poisoned patients regardless of the time from OP ingestion to
      administration, compared with those of patients who did not receive AC-sorbitol.
      However, this study enrolled a small number of patients who received AC-sorbitol;
      further qualified trials with a sufficient number of patients are therefore
      needed.

PMID- 25608918
TI  - Identification of a new soybean kunitz trypsin inhibitor mutation and its effect
      on bowman-birk protease inhibitor content in soybean seed.
AB  - Soybean seed contains antinutritional compounds that inactivate digestive
      proteases, principally corresponding to two families: Kunitz trypsin inhibitors
      (KTi) and Bowman-Birk inhibitors (BBI). High levels of raw soybean/soybean meal
      in feed mixtures can cause poor weight gain and pancreatic abnormalities via
      inactivation of trypsin/chymotrypsin enzymes. Soybean protein meal is routinely
      heat-treated to inactivate inhibitors, a practice that is energy-intensive and
      costly and can degrade certain essential amino acids. In this work, we screened
      seed from 520 soybean accessions, using a combination of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblots with anti-Kunitz
      trypsin inhibitor antibodies. A soybean germplasm accession was identified with a
      mutation affecting an isoform annotated as nonfunctional (KTi1), which was
      determined to be synergistic with a previously identified mutation (KTi3-). We
      observed significant proteome rebalancing in all KTi mutant lines, resulting in
      dramatically increased BBI protein levels. 

PMID- 25608919
TI  - Paradoxes in the origin of life.

PMID- 25608920
TI  - Spontaneous overcrowding in liposomes as possible origin of metabolism.
AB  - We emphasize here that, in considering the initial prebiotic reactions, it is
      fundamental to take into consideration the critical threshold concentration, in
      particular when talking about self-replication and initial metabolism. It is also
      shown that the in situ formation of vesicles in a solution containing
      macromolecular solutes, permits to obtain filled vesicles which are overcrowded
      of those solutes and therefore viable for complex biochemical reactions. 

PMID- 25608921
TI  - Mechanics of epithelial closure over non-adherent environments.
AB  - The closure of gaps within epithelia is crucial to maintain its integrity during
      biological processes such as wound healing and gastrulation. Depending on the
      distribution of extracellular matrix, gap closure occurs through assembly of
      multicellular actin-based contractile cables or protrusive activity of border
      cells into the gap. Here we show that the supracellular actomyosin contractility
      of cells near the gap edge exerts sufficient tension on the surrounding tissue to
      promote closure of non-adherent gaps. Using traction force microscopy, we observe
      that cell-generated forces on the substrate at the gap edge first point away from
      the centre of the gap and then increase in the radial direction pointing into the
      gap as closure proceeds. Combining with numerical simulations, we show that the
      increase in force relies less on localized purse-string contractility and more on
      large-scale remodelling of the suspended tissue around the gap. Our results
      provide a framework for understanding the assembly and the mechanics of cellular
      contractility at the tissue level. 

PMID- 25608923
TI  - Presepsin: solving a soluble (CD14) problem in sepsis?

PMID- 25608922
TI  - Surface enhanced electrochemiluminescence of Ru(bpy)3(2+).
AB  - Surface enhanced spectroscopy such as surface enhanced Raman spectrum (SERS) and
      surface enhanced fluorescence have been investigated extensively in the past two
      decades. Herein, we present experimental evidence to demonstrate the existence of
      a new surface enhanced spectroscopy, namely, surface enhanced
      electrochemiluminescence (SEECL). Our investigation indicates that the
      electrochemiluminescence (ECL) response of the Ru(bpy)3(2+)-tri-n-propylamine
      (TPrA) system could be significantly enhanced when the working electrode is
      modified with gold nanoparticle-SiO2 core-shell nanocomposites (AuNP@SiO2). It is
      worth noting that comparing with a working electrode modified with pure SiO2
      nanoparticles, the electrochemical responses of the two electrodes were quite
      similar, but the ECL signal of the AuNP@SiO2 modified electrode was ~5 times
      higher than that of the SiO2 nanoparticles modified electrode. Thus we infer that
      the localized surface plasmon resonance (LSPR) of the AuNPs could be a major
      contribution to the ECL enhancement. Our investigations also demonstrate that the
      ECL enhancement is closely related to the thickness of the SiO2 layer. As much as
      10 times ECL enhancement (comparing with the ECL intensity of bare electrode) is
      observed under the optimal conditions. The possible mechanism of the SEECL
      phenomenon is also discussed. 

PMID- 25608924
TI  - What's new in hemorrhagic shock?

PMID- 25608925
TI  - Measurement of AKI biomarkers in the ICU: still striving for appropriate clinical
      indications.

PMID- 25608927
TI  - Always look at the bright side of drugs?

PMID- 25608928
TI  - High dietary intake of vitamin C suppresses age-related thymic atrophy and
      contributes to the maintenance of immune cells in vitamin C-deficient senescence
      marker protein-30 knockout mice.
AB  - Vitamin C (VC) is an essential nutrient for humans and certain other animals. It
      has antioxidant properties and has been reported to ameliorate oxidative damage
      to lipids, DNA and proteins. However, the effects of VC on immune function are
      poorly understood, especially the influence of long-term high-dose VC intake on
      the number and function of immune cells. In the present study, to evaluate the
      immune effects of VC, VC-deficient senescence marker protein-30 knockout
      (SMP30KO) mice were fed a diet containing the recommended level of VC (20 mg/kg
      per d; 0.02 % VC) or a high level of VC (200 mg/kg per d; 0.2 % VC) for 1 year.
      The plasma VC concentration of the 0.02 % group was the same as that of age
      matched C57BL/6 mice after 1 year of feeding; however, plasma VC concentration
      and thymus weight were significantly higher in the 0.2 % VC group than in the
      0.02 % VC group. The total counts of leucocytes, lymphocytes, granulocytes and
      monocytes in the peripheral blood, as well as the number of splenocytes and
      thymocytes, were all significantly higher in the 0.2 % VC group than in the 0.02
      % VC group. In addition, the number of naive T cells in peripheral blood
      lymphocytes, the number of memory T-cell populations in splenocytes, and the
      number of cluster of differentiation (CD)4+CD8+ or CD4+CD8- or CD4-CD8+ T cells
      in thymocytes were all markedly higher in the 0.2 % VC group than in the 0.02 %
      VC group after 1 year of dietary treatment. These results suggest that a long
      term high-dose intake of VC is effective in the maintenance of immune cells,
      partly through the suppression of age-related thymic involution in VC-deficient
      SMP30KO mice.

PMID- 25608926
TI  - Genome-wide meta-analysis in alopecia areata resolves HLA associations and
      reveals two new susceptibility loci.
AB  - Alopecia areata (AA) is a prevalent autoimmune disease with 10 known
      susceptibility loci. Here we perform the first meta-analysis of research on AA by
      combining data from two genome-wide association studies (GWAS), and replication
      with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls.
      The strongest region of association is the major histocompatibility complex,
      where we fine-map four independent effects, all implicating human leukocyte
      antigen-DR as a key aetiologic driver. Outside the major histocompatibility
      complex, we identify two novel loci that exceed the threshold of statistical
      significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as
      well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12).
      Candidate susceptibility gene expression analysis in these regions demonstrates
      expression in relevant immune cells and the hair follicle. We integrate our
      results with data from seven other autoimmune diseases and provide insight into
      the alignment of AA within these disorders. Our findings uncover new molecular
      pathways disrupted in AA, including autophagy/apoptosis, transforming growth
      factor beta/Tregs and JAK kinase signalling, and support the causal role of
      aberrant immune processes in AA. 

PMID- 25608930
TI  - Helicobacter pylori infection and gastroesophageal reflux disease - Barrett's
      esophagus sequence "dilemma"

PMID- 25608931
TI  - Abdul Ghafur: Adventurous, emotional, outspoken.

PMID- 25608929
TI  - Long-term survival after endoscopic resection for early gastric cancer in the
      remnant stomach: comparison with radical surgery.
AB  - BACKGROUND: Endoscopic resection (ER) has recently become standard treatment,
      even for early gastric cancer (EGC) in the remnant stomach. We aimed to compare
      long-term survival after ER versus radical surgery for EGC in the remnant
      stomach. METHODS: We retrospectively compared overall and cause-specific survival
      of patients who had undergone ER or radical surgery for EGC in the remnant
      stomach from 1998 to 2012. RESULTS: During the study period, 32 patients with
      intramucosal (M), two with shallow submucosal (SM1) and eight with deep
      submucosal (SM2) cancers had undergone ER (ER group) whereas six with M and seven
      with SM2 cancers had undergone surgery (surgery group). All patients were
      followed up for a median of 60 months; during follow up, 15 patients died,
      including three in the ER group with SM2 cancer who died of gastric cancer. The
      overall 5-year survival rates of M-SM1 and SM2 cancer patients in the ER and
      surgery groups were 89%, 48%, 80%, and 67%, respectively (P=0.079). The disease
      specific 5-year survival rates of M-SM1 and SM2 cancer patients in the ER and
      surgery groups were 100%, 48%, 100%, and 100%, respectively (P=0.000). Operation
      time and hospital stay were significantly shorter in the ER than the surgery
      group (P<0.001). Grade 2 perforation occurred in two patients in the ER group and
      Grade 3 anastomotic leakage in two patients in the surgery group. CONCLUSION: ER
      provides excellent outcomes, comparable with those of radical surgery, in
      patients with M-SM1 gastric cancer in the remnant stomach; however, patients with
      SM2 cancer require radical surgery.

PMID- 25608932
TI  - Potential for nutrient recovery and biogas production from blackwater, food waste
      and greywater in urban source control systems.
AB  - In the last decades, the focus on waste and wastewater treatment systems has
      shifted towards increased recovery of energy and nutrients. Separation of urban
      food waste (FW) and domestic wastewaters using source control systems could aid
      this increase; however, their effect on overall sustainability is unknown. To
      obtain indicators for sustainability assessments, five urban systems for
      collection, transport, treatment and nutrient recovery from blackwater, greywater
      and FW were investigated using data from implementations in Sweden or northern
      Europe. The systems were evaluated against their potential for biogas production
      and nutrient recovery by the use of mass balances for organic material, nutrients
      and metals over the system components. The resulting indicators are presented in
      units suitable for use in future sustainability studies or life-cycle assessment
      of urban waste and wastewater systems. The indicators show that source control
      systems have the potential to increase biogas production by more than 70%
      compared with a conventional system and give a high recovery of phosphorus and
      nitrogen as biofertilizer. The total potential increase in gross energy
      equivalence for source control systems was 20-100%; the greatest increase shown
      is for vacuum-based systems. 

PMID- 25608933
TI  - N-heterocyclic carbene (NHC) complexes of group 4 transition metals.
AB  - Since the discovery of a stable N-heterocyclic carbene (NHC), the use of NHCs in
      chemistry has developed rapidly over the past two decades. These interesting
      compounds are predominantly employed in organometallic chemistry as ligands for
      various metal centers, and as organocatalysts for a variety of transformations.
      In particular, the NHC transition metal complexes have received widespread
      attention, and significant progress has been made in the development of group 4
      NHC-complexes in the last few years. These group 4 NHC-complexes are of interest
      because of their unique structural properties, and their potential application in
      organic transformations and catalysis. This review covers the superior design
      strategies for NHC ligands to stabilize early transition metals and well-defined
      group 4 metal complexes with mono- and multi-dentate NHC ligands. In this
      context, four types of NHC-complexes, i.e., carbon-functionalized NHCs, nitrogen
      functionalized NHCs, oxygen-functionalized NHCs and nitrogen/oxygen
      functionalized unsymmetric NHCs, are described. In addition, the use of group 4
      NHC-complexes as catalysts in olefin (co)polymerization, ring-opening
      polymerization of rac-lactide, copolymerization of epoxides and CO2, as well as
      hydroamination/cyclization of aminoalkenes, is presented. Furthermore,
      limitations and challenges are discussed. 

PMID- 25608934
TI  - Erratum to: Commonalities and Challenges in the Development of Clinical Trial
      Measures in Neurology.

PMID- 25608935
TI  - Stuck in the mire.

PMID- 25608936
TI  - A systems approach to drug discovery in Alzheimer's disease.
AB  - In the articles included in this volume, one feels a strong frustration among the
      writers with the slow course of therapeutics development for Alzheimer's disease
      and with the clinical failure of targeted therapeutic agents despite substantial
      progress in our understanding of the biology and biochemistry of the disease. 

PMID- 25608937
TI  - Micronutrient fortification of food in Southeast Asia: recommendations from an
      expert workshop.
AB  - Micronutrient deficiencies remain a significant public health issue in Southeast
      Asia, particularly in vulnerable populations, such as women of reproductive age
      and young children. An important nutrition-specific intervention to address
      micronutrient malnutrition is fortification of staple foods and condiments. In
      October 2013, the International Life Sciences Institute (ILSI) Southeast Asia
      Region held a workshop on micronutrient fortification of food in Bangkok,
      Thailand. The objective was to engage multiple stakeholders in a discussion on
      food fortification and its importance as a public health intervention in
      Southeast Asia, and to identify and address key challenges/gaps in and potential
      opportunities for fortification of foods in ASEAN countries. Key challenges that
      were identified include: "scaling up" and mobilizing sustainable support for
      fortification programs in the form of multi-stakeholder partnerships, effecting
      policy change to support mandatory fortification, long-term monitoring of the
      programs' compliance and efficacy in light of limited resources, and increasing
      awareness and uptake of fortified products through social marketing campaigns.
      Future actions recommended include the development of terms of engagement and
      governance for multi-stakeholder partnerships, moving towards a sustainable
      business model and more extensive monitoring, both for effectiveness and efficacy
      and for enforcement of fortification legislation. 

PMID- 25608938
TI  - Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a
      meta-analysis of randomised clinical trials.
AB  - There is an urgent need to treat individuals with high blood pressure (BP) with
      effective dietary strategies. Previous studies suggest a small, but significant
      decrease in BP after lactotripeptides (LTP) ingestion, although the data are
      inconsistent. The study aim was to perform a comprehensive meta-analysis of data
      from all relevant randomised controlled trials (RCT). Medline, Cochrane library,
      EMBASE and Web of Science were searched until May 2014. Eligibility criteria were
      RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and
      diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria,
      which resulted in 33 sets of data. The pooled treatment effect for SBP was -2.95
      mmHg (95% CI: -4.17, -1.73; p < 0.001), and for DBP was -1.51 mmHg (95% CI: 
      2.21, -0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in
      Japanese studies was significantly greater, compared with European studies (p =
      0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to
      LTP supplementation was statistically non-significant (p = 0.101 for SBP and p =
      0.166 for DBP). Both publication bias and "small-study effect" were identified,
      which shifted the treatment effect towards less significant SBP and non
      significant DBP reduction after LTP consumption. LTP may be effective in BP
      reduction, especially in Japanese individuals; however sub-group, meta-regression
      analyses and statistically significant publication biases suggest
      inconsistencies. 

PMID- 25608939
TI  - Maltol, a food flavoring agent, attenuates acute alcohol-induced oxidative damage
      in mice.
AB  - The purpose of this study was to evaluate the hepatoprotective effect of maltol,
      a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol
      used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and
      analyzed by high performance liquid chromatography (HPLC) and mass spectrometry.
      For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50
      mg/kg; 15 days) drastically prevented the elevated activities of aspartate
      transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and
      triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) in liver tissue
      (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT),
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by
      maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological
      examination revealed that maltol pretreatment significantly inhibited alcohol
      induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment
      of maltol effectively relieved alcohol-induced oxidative damage in a dose
      dependent manner. Maltol appeared to possess promising anti-oxidative and anti
      inflammatory capacities. It was suggested that the hepatoprotective effect
      exhibited by maltol on alcohol-induced liver oxidative injury may be due to its
      potent antioxidant properties. 

PMID- 25608940
TI  - 13C-enrichment of urinary uric acid after L-[Ring-2-13C]histidine dose in adult
      humans.
AB  - We determined whether ring-2 carbon of histidine is folate-dependently
      transferred to carbons 8 (C8) and/or 2 (C2) in urinary uric acid in humans. Two
      adults collected each urine void for four days. Aliquots of urine for the first
      day were used for baseline values; then the subjects ingested 0.7 g (3.3 mmol) of
      l-[ring-2-13C]histidine and collected urine for three experimental days. Aliquots
      were analyzed for percentage 13C-content at C2 and C8 by a liquid-chromatography
      mass spectrometry method. Percentage enrichment was determined by subtracting
      time-of-day paired baseline percentage 13C-content from experimental percentage
      13C-content for each void. C2 was predominantly 13C-enriched in the majority of
      voids. The percentage enrichments at C2 for two subjects were 0.14 (+/-0.028
      [SEM], n = 26) and 0.18 (+/-0.049, n = 21), whereas at C8, they were 0.008 (+/
      0.006) and -0.005 (+/-0.008), respectively. The mean C2-enrichments were
      significantly greater than zero (p < 0.01), whereas those of C8 were not (p >
      0.2). The enrichment had a diurnal rhythm peaking in the morning. Our results may
      be useful in the estimation of the timing for the administration of drugs that
      interfere with purine nucleotide biosynthesis in the treatment of cancer and
      autoimmune disease. 

PMID- 25608942
TI  - Semi-crystalline polymethylene-b-poly(acrylic acid) diblock copolymers:
      aggregation behavior, confined crystallization and controlled growth of
      semicrystalline micelles from dilute DMF solution.
AB  - In this paper, we have systematically investigated the aggregation behavior,
      confined crystallization and controlled growth of a novel polyolefin analogue
      containing block copolymers (BCPs), i.e., polymethylene-b-poly(acrylic acid)
      diblock copolymers (PM-b-PAA). On cooling from a homogenous DMF solution at 80 
      degrees C, PM-b-PAA was found to crystallize and aggregate with well-defined disk
      like micelles. The aggregate behavior and in-plane morphology of PM-b-PAA could
      be easily controlled by modifying the block ratio, solution pH and solvent
      composition (DMF-water), by manipulating the crystallization of PM block and the
      stretching degree of solvated PAA corona. Further investigation of the
      crystalline feature of PM-b-PAA indicated that the crystallization of PM was
      retarded by tethered amorphous PAA segments. The crystalline micelle could
      construct a nano-confined environment with PM folding as the core into a
      thickness of the mono-layered polyethylene. Finally, when cultured in dilute DMF
      solution at 50  degrees C, the initial crystalline micelles, being as self-seeds,
      could follow a living growth mechanism and develop into single crystals, with
      well-defined lozenge-shaped morphology. 

PMID- 25608941
TI  - Egg and egg-derived foods: effects on human health and use as functional foods.
AB  - Eggs are sources of protein, fats and micronutrients that play an important role
      in basic nutrition. However, eggs are traditionally associated with adverse
      factors in human health, mainly due to their cholesterol content. Nowadays,
      however, it is known that the response of cholesterol in human serum levels to
      dietary cholesterol consumption depends on several factors, such as ethnicity,
      genetic makeup, hormonal factors and the nutritional status of the consumer.
      Additionally, in recent decades, there has been an increasing demand for
      functional foods, which is expected to continue to increase in the future, owing
      to their capacity to decrease the risks of some diseases and socio-demographic
      factors such as the increase in life expectancy. This work offers a brief
      overview of the advantages and disadvantages of egg consumption and the potential
      market of functional eggs, and it explores the possibilities of the development
      of functional eggs by technological methods. 

PMID- 25608943
TI  - Cardiovascular outcomes with antihypertensive therapy in type 2 diabetes: an
      analysis of intervention trials.
AB  - In studies of antihypertensive therapy, relative cardiovascular (CV) risk
      reduction is largely independent of attained systolic blood pressure (SBP). How
      this translates to absolute risk reduction (ARR) in diabetes is not clear. We
      have compared 5-year CV outcomes in 10 studies of intensive versus moderate or
      active versus placebo therapy in subjects with type 2 diabetes and attained SBP <
      or ? 140 mm Hg. Attained SBP ? 140 mm Hg occurred in five early studies (HOT n =
      1001, UKPDS n = 1148, SHEP n = 583, SYSTEUR n = 422, MICRO_HOPE n = 3377) and
      attained SBP<140 mm Hg occurred in five recent studies (ABCD-NT n = 480, ADVANCE
      n = 11,140 INVEST n = 4266, ACCORD n = 4733, ROADMAP n= 4447). In each study, ARR
      was calculated from group mean data and expressed as % change in CV events over 5
      years per 10 mm Hg decrease in attained SBP. In studies with attained SBP ? 140
      mm Hg, ARR was 13 +/- 2.6% per 10 mm Hg, and the number needed to treat (NNT) to
      prevent one event in 5 years was 8. In studies with attained SBP < 140 mm Hg, ARR
      was 1.6 +/- 1 .9% per 10 mm Hg (P = 0.0007), and NNT was 68. The present analysis
      indicates that CV outcomes reach a plateau after attaining SBP of 140 mm Hg in
      patients with type 2 diabetes.

PMID- 25608944
TI  - Multidimensional optical sensing platform for detection of heparin and reversible
      molecular logic gate operation based on the phloxine B/polyethyleneimine system.
AB  - A multidimensional optical sensing platform which combines the advantages of
      resonance Rayleigh scattering (RRS), fluorescence, and colorimetry has been
      designed for detection of heparin. Phloxine B, a fluorescein derivative showing
      the special RRS spectrum in the long wavelength region, was selected to develop
      an easy-to-get system which can achieve switch-on sensing to obtain high
      sensitivity. The noise level of RRS in the long wavelength region is much weaker,
      and the reproducibility is much better; in this way, the sensitivity and
      selectivity can be improved. In the absence of heparin, the phloxine B and
      polyethyleneimine (PEI) form a complex through electrostatic interaction. Thus,
      the RRS signal at 554 nm is low; the phloxine B fluorescence is quenched, and the
      absorption signal is low. In the presence of heparin, competitive binding
      occurred between phloxine B and heparin toward PEI; then, phloxine B is gradually
      released from the phloxine B/PEI complex, causing obvious enhancement of the RRS,
      fluorescence, and absorption signals. Besides, the desorption of phloxine B is
      less effective for the heparin analogues, such as hyaluronic acid and chondroitin
      sulfate. In addition, the system presents a low detection limit of heparin to 5.0
      * 10(-4) U mL(-1) and can also be applied to the detection of heparin in heparin
      sodium injection and 50% human serum samples with satisfactory results. Finally,
      the potential application of this method in reversible on-off molecular logic
      gate fabrication was discussed using the triple-channel optical signals as
      outputs. 

PMID- 25608945
TI  - Microbial electrosynthesis of butyrate from carbon dioxide.
AB  - This work proves for the first time the bioelectrochemical production of butyrate
      from CO2 as a sole carbon source. The highest concentration of butyrate achieved
      was 20.2 mMC, with a maximum butyrate production rate of 1.82 mMC d(-1). The
      electrochemical characterisation demonstrated that the CO2 reduction to butyrate
      was hydrogen driven. Production of ethanol and butanol was also observed opening
      up the potential for biofuel production. 

PMID- 25608946
TI  - "It's MAGIC"--development of a manageable geriatric assessment for general
      practice use.
AB  - BACKGROUND: Geriatric assessments are established tools in institutional care
      since they enable standardized detection of relevant age-related disorders.
      Geriatric assessments could also be helpful in general practice. However, they
      are infrequently used in this setting, mainly due to their lengthy
      administration. The aim of the study was the development of a "manageable
      geriatric assessment--MAGIC", specially tailored to the requirements of daily
      primary care. METHODS: MAGIC was developed based on the comprehensive
      Standardized Assessment for Elderly People in Primary Care (STEP), using four
      different methodological approaches: We relied on A) the results of the PRISCUS
      study by assessing the prevalence of health problems uncovered by STEP, the
      importance of the respective problems rated by patients and general
      practitioners, as well as the treatment procedures initiated subsequently to the
      assessment. Moreover, we included findings of B) a literature analysis C) a
      review of the STEP assessment by experienced general practitioners and D) focus
      groups with general practitioners. RESULTS: The newly created MAGIC assessment
      consists of 9 items and covers typical geriatric health problems and syndromes:
      function, falls, incontinence, cognitive impairment, impaired ears and eyes,
      vaccine coverage, emotional instability and isolation. CONCLUSIONS: MAGIC
      promises to be a helpful screening instrument in primary care consultations
      involving elderly multimorbid patients. Applicable within a minimum of time it
      still covers health problems highly relevant with regard to a potential loss of
      autonomy. Feasibility will be tested in the context of a large, still ongoing
      randomized controlled trial on "reduction of potentially inadequate medication in
      elderly patients" (RIME study; DRKS-ID: DRKS00003610) in general practice.

PMID- 25608947
TI  - Everybody wants it done but nobody wants to do it: an exploration of the barrier
      and enablers of critical components towards creating a clinical pathway for
      anxiety and depression in cancer.
AB  - BACKGROUND: This study aimed to explore barriers to and enablers for future
      implementation of a draft clinical pathway for anxiety and depression in cancer
      patients in the Australian context. METHODS: Health professionals reviewed a
      draft clinical pathway and participated in qualitative interviews about the
      delivery of psychosocial care in their setting, individual components of the
      draft pathway, and barriers and enablers for its future implementation. RESULTS:
      Five interrelated themes were identified: ownership; resources and
      responsibility; education and training; patient reluctance; and integration with
      health services beyond oncology. CONCLUSIONS: The five themes were perceived as
      both barriers and enablers and provide a basis for an implementation plan that
      includes strategies to overcome barriers. The next steps are to design and
      deliver the clinical pathway with specific implementation strategies that address
      team ownership, endorsement by leaders, education and training modules designed
      for health professionals and patients and identify ways to integrate the pathway
      into existing cancer services.

PMID- 25608948
TI  - Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and
      neuronal apoptosis.
AB  - Apoptosis mediates the precise and programmed natural death of neurons and is a
      physiologically important process in neurogenesis during maturation of the
      central nervous system. However, premature apoptosis and/or an aberration in
      apoptosis regulation are implicated in the pathogenesis of neurodegeneration.
      Thus, it is important to identify neuronal pathways/factors controlling
      apoptosis. Pink1 [phosphatase and tensin homologue (PTEN)-induced kinase 1] is a
      ubiquitously expressed gene and has been reported to have a physiological role in
      mitochondrial maintenance, suppressing mitochondrial oxidative stress, fission
      and autophagy. However, how Pink1 is involved in neuronal survival against
      oxidative stress remains not well understood. In the present paper, we
      demonstrate that thapsigargin, a specific irreversible inhibitor of endoplasmic
      reticulum (ER) calcium-ATPase, could lead to dramatic oxidative stress and
      neuronal apoptosis by ectopic calcium entry. Importantly, the neuronal toxicity
      of thapsigargin inhibits antioxidant gene Pink1 expression. Although Pink1
      knockdown enhances the neuronal apoptosis by thapsigargin, its overexpression
      restores it. Our findings have established the neuronal protective role of Pink1
      against oxidative stress and afford rationale for developing new strategy to the
      therapy of neurodegenerative diseases. 

PMID- 25608949
TI  - Distinct itinerant spin-density waves and local-moment antiferromagnetism in an
      intermetallic ErPd2Si2 single crystal.
AB  - Identifying the nature of magnetism, itinerant or localized, remains a major
      challenge in condensed-matter science. Purely localized moments appear only in
      magnetic insulators, whereas itinerant moments more or less co-exist with
      localized moments in metallic compounds such as the doped-cuprate or the iron
      based superconductors, hampering a thorough understanding of the role of
      magnetism in phenomena like superconductivity or magnetoresistance. Here we
      distinguish two antiferromagnetic modulations with respective propagation wave
      vectors at Q+/- = (H +/- 0.557(1), 0, L +/- 0.150(1)) and QC = (H +/- 0.564(1),
      0, L), where (H, L) are allowed Miller indices, in an ErPd2Si2 single crystal by
      neutron scattering and establish their respective temperature- and field
      dependent phase diagrams. The modulations can co-exist but also compete depending
      on temperature or applied field strength. They couple differently with the
      underlying lattice albeit with associated moments in a common direction. The Q+/-
      modulation may be attributed to localized 4f moments while the QC correlates well
      with itinerant conduction bands, supported by our transport studies. Hence,
      ErPd2Si2 represents a new model compound that displays clearly-separated
      itinerant and localized moments, substantiating early theoretical predictions and
      providing a unique platform allowing the study of itinerant electron behavior in
      a localized antiferromagnetic matrix. 

PMID- 25608950
TI  - Clinical directors' views of centralisation and commissioning of cleft services
      in the U.K.
AB  - BACKGROUND: To determine the views of Clinical Directors working in the United
      Kingdom (U.K.) Cleft Service with regard to centralisation, commissioning and
      impact on cleft service provision. METHODS: In-depth qualitative interviews were
      conducted with 11 Clinical Directors representing regional cleft services.
      Interviews were transcribed verbatim, a coding frame was developed by two
      researchers and transcripts were coded using a thematic, 'interpretive' approach.
      RESULTS: Clinical Directors perceived the commissioning of cleft services in the
      U.K. to be dependent upon historical agreements and individual negotiation
      despite service centralisation. Furthermore, Clinical Directors perceived
      unfairness in the commissioning and funding of cleft services and reported
      inconsistencies in funding models and service costs that have implications for
      delivering an equitable cleft service with an effective Multidisciplinary Team.
      CONCLUSIONS: National Health Service (NHS) commissioning bodies can learn lessons
      from the centralisation of cleft care. Clinical Directors' accounts of their
      relationships with specialist commissioning bodies and their perspectives of
      funding cleft services may serve to increase parity and improve the commissioning
      of cleft services in the U.K.

PMID- 25608951
TI  - A stacking flow immunoassay for the detection of dengue-specific immunoglobulins
      in salivary fluid.
AB  - Paper-based immunoassays, usually in the form of lateral flow tests, are
      currently the standard platform for home diagnostics. However, conventional
      lateral tests are often complicated by severe non-specific adsorption of detector
      particles when applied to test samples containing salivary fluid. It is believed
      that a high concentration of proteinaceous substances in salivary fluid causes
      particle aggregation and adhesion. In this study, we developed a stacking flow
      platform for single-step detection of a target antibody in salivary fluid.
      Stacking flow circumvents the need for separate sample pre-treatments, such as
      filtration or centrifugation, which are often required prior to testing saliva
      samples using paper-based immunoassays. This is achieved by guiding the samples
      and reagents to the test strip through different paths. By doing so, salivary
      substances that interfere with the particle-based sensing system are removed
      before they come into contact with the detection reagents, which greatly reduces
      the background. In addition, the stacking flow configuration enables uniform flow
      with a unique flow regulator, which leads to even test lines with good
      quantification capability, enabling the detection of ~20 ng mL(-1) alpha
      fetoprotein in the serum. We have successfully applied the stacking flow device
      to detect dengue-specific immunoglobulins that are present in salivary fluid. 

PMID- 25608952
TI  - The evaluation of anti-angiogenic effects of Endostar on rabbit VX2 portal vein
      tumor thrombus using perfusion MSCT.
AB  - BACKGROUND: There were many treatments for hepatocellular carcinoma with portal
      vein tumor thrombus (PVTT), in which targeted anti-angiogenic drug therapy is
      becoming a popular research topic. However, an objective and non-invasive method
      that can evaluate the treatment effects is still lacking. METHODS: Eighteen New
      Zealand white rabbits implanted with VX2 tumor thrombus in portal vein were
      randomly assigned into 3 groups: Endostar, saline, or control, six in each group.
      Multi-slice CT (MSCT) perfusion scanning was performed to measure the differences
      in blood flow (TBF), tissue blood volume (TBV), and capillary permeability time
      the surface (PS) before and after Endostar treatment, between Endostar and saline
      treatment. Two weeks after treatment, both Endostar and saline groups underwent
      CT perfusion scan. The rabbits then were sacrificed by air embolism, and
      specimens of tumor thrombosis were collected. Immunohistochemistry assay was also
      performed to compare the expression of vascular endothelial growth factor (VEGF)
      in PVTT after Endostar, saline and placebo treatment. RESULTS: In Endostar group,
      PVTT CT perfusion parameters (TBF, TBV, PS) significantly decreased after the
      treatment (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS)
      were significantly lower in Endostar group than in Saline group (p <0.05). VEGF
      is mainly expressed in cytoplasma. After Endostar treatment, the expression of
      VEGF in PVTT was markedly reduced. There was also significant difference on post
      treatment VEGF protein expression measured by Immunohistochemistry assay between
      Endostar group and control group (p <0.05). Post-treatment PVTT CT perfusion
      parameters (TBF, TBV, PS) were positively correlated with VEGF protein expression
      in all 3 groups (rs > 0, p <0.05). CONCLUSIONS: Multi-slice CT perfusion imaging
      can evaluate the anti-angiogenic effects of Endostar for the VX2 tumor thrombus
      in portal vein, and provide quantitative functional information.

PMID- 25608953
TI  - Bioaccessibility of polyphenols associated with dietary fiber and in vitro
      kinetics release of polyphenols in Mexican 'Ataulfo' mango (Mangifera indica L.)
      by-products.
AB  - The biological properties of polyphenol (PP) depend on its bioaccessibility and
      bioavailability. Therefore, part of PP released from the food matrix in the
      gastrointestinal tract through enzymatic hydrolysis is at least partially
      absorbed. The aim of this study is to determine the bioaccessibility of PP
      associated with dietary fiber (DF) and the kinetics release of PP in mango
      (Mangifera indica L.) 'Ataulfo' by-products by an in vitro model. Soluble and
      insoluble DF values were 7.99 and 18.56% in the mango paste and 6.98 and 22.78%
      in the mango peel, respectively. PP associated with soluble and insoluble DF was
      6.0 and 3.73 g GAE per 100 g in the paste and 4.72 and 4.50 g GAE per 100 g in
      the peel. The bioaccessibility of PP was 38.67% in the pulp paste and 40.53% in
      the peel. A kinetics study shows a release rate of 2.66 and 3.27 g PP min(-1) in
      the paste and peel, respectively. The antioxidant capacity of the paste increased
      as digestion reached a value of 2.87 mmol TE min(-1) at 180 min. The antioxidant
      capacity of the peel had its maximum (28.94 mmol TE min(-1)) between 90 and 120
      min of digestion; it started with a value of 2.58 mmol TE min(-1), and thereafter
      increased to 4.20 mmol TE min(-1) at 180 min. The major PPs released during the
      digestion of paste were gallic and hydroxybenzoic acids, while in the peel, they
      were hydroxycinnamic and vanillic acids. It was concluded that these phenolic
      compounds are readily available for absorption in the small intestine and exert
      different potential health benefits. 

PMID- 25608955
TI  - A quasi-QSPR modelling for the photocatalytic decolourization rate constants and
      cellular viability (CV%) of nanoparticles by CORAL.
AB  - Most quantitative structure-property/activity relationships (QSPRs/QSARs) predict
      various endpoints related to organic compounds. Gradually, the variety of organic
      compounds has been extended to inorganic, organometallic compounds and polymers.
      However, the so-called molecular descriptors cannot be defined for super-complex
      substances such as different nanomaterials and peptides, since there is no simple
      and clear representation of their molecular structure. Some possible ways to
      define approaches for a predictive model in the case of super-complex substances
      are discussed. The basic idea of the approach is to change the traditionally used
      paradigm 'the endpoint is a mathematical function of the molecular structure'
      with another paradigm 'the endpoint is a mathematical function of available
      eclectic information'. The eclectic data can be (i) conditions of a synthesis,
      (ii) technological attributes, (iii) size of nanoparticles, (iv) concentration,
      (v) attributes related to cell membranes, and so on. Two examples of quasi
      QSPR/QSAR analyses are presented and discussed. These are (i) photocatalytic
      decolourization rate constants (DRC) (10(-5)/s) of different nanopowders; and
      (ii) the cellular viability under the effect of nano-SiO(2).

PMID- 25608956
TI  - State of the art in the application of QSAR techniques for predicting mixture
      toxicity in environmental risk assessment.
AB  - The focus of regulatory chemical risk assessment has been mainly placed on single
      chemicals rather than mixtures. However, living organisms and the environment
      might be exposed to mixtures of chemicals. Many scientific studies have revealed
      that mixture toxicity can arise from the combined effects of components present
      at levels below their individual no-effect concentrations. Predictive approaches
      will be essential for estimating mixture toxicity, as the number of possible
      mixtures is extremely large. Although predictive models are virtually
      indispensable for estimating mixture toxicity for both scientific and regulatory
      purposes, risk assessors encounter substantial difficulties in using conventional
      models, mainly due to the lack of information on the modes of toxic action of the
      mixture constituents. Alternative models that use different information instead
      of the modes of action thus need to be developed. The objective of this study is
      to investigate the state of the art in predictive models based on quantitative
      structure-activity relationship techniques for estimating the toxicity of mixture
      components, and to identify future challenges hindering more reliable mixture
      risk assessment for environmental risk assessment. Alternative models need to be
      developed not only to overcome the limitations of conventional models, but also
      to improve their performance. 

PMID- 25608954
TI  - Perioperative management in myasthenia gravis: republication of a systematic
      review and a proposal by the guideline committee of the Japanese Association for
      Chest Surgery 2014.
AB  - Thymectomy is regarded as a useful therapeutic option for myasthenia gravis (MG),
      though perioperative management in MG patients is largely empirical. While
      evidence-based medicine is limited in the perioperative management of MG
      patients, treatment guidelines are required as a benchmark. We selected issues
      faced by physicians in clinical practice in the perioperative management of
      extended thymectomy for MG, and examined them with a review of the literature.
      The present guidelines have reached the stage of consensus within the Japanese
      Association for Chest Surgery. 

PMID- 25608957
TI  - Magnetic imaging: a new tool for UK national nuclear security.
AB  - Combating illicit trafficking of Special Nuclear Material may require the ability
      to image through electromagnetic shields. This is the case when the trafficking
      involves cargo containers. Thus, suitable detection techniques are required to
      penetrate a ferromagnetic enclosure. The present study considers techniques that
      employ an electromagnetic based principle of detection. It is generally assumed
      that a ferromagnetic metallic enclosure will effectively act as a Faraday cage to
      electromagnetic radiation and therefore screen any form of interrogating
      electromagnetic radiation from penetrating, thus denying the detection of any
      eventual hidden material. In contrast, we demonstrate that it is actually
      possible to capture magnetic images of a conductive object through a set of
      metallic ferromagnetic enclosures. This validates electromagnetic interrogation
      techniques as a potential detection tool for National Nuclear Security
      applications. 

PMID- 25608959
TI  - Progress of new label-free techniques for biosensors: a review.
AB  - The detection techniques used in biosensors can be broadly classified into label
      based and label-free. Label-based detection relies on the specific properties of
      labels for detecting a particular target. In contrast, label-free detection is
      suitable for the target molecules that are not labeled or the screening of
      analytes which are not easy to tag. Also, more types of label-free biosensors
      have emerged with developments in biotechnology. The latest developed techniques
      in label-free biosensors, such as field-effect transistors-based biosensors
      including carbon nanotube field-effect transistor biosensors, graphene field
      effect transistor biosensors and silicon nanowire field-effect transistor
      biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress
      based biosensors and other type of biosensors based on the nanotechnology are
      discussed. The sensing principles, configurations, sensing performance,
      applications, advantages and restriction of different label-free based biosensors
      are considered and discussed in this review. Most concepts included in this
      survey could certainly be applied to the development of this kind of biosensor in
      the future. 

PMID- 25608958
TI  - Insulin resistance, selfish brain, and selfish immune system: an evolutionarily
      positively selected program used in chronic inflammatory diseases.
AB  - Insulin resistance (IR) is a general phenomenon of many physiological states,
      disease states, and diseases. IR has been described in diabetes mellitus,
      obesity, infection, sepsis, trauma, painful states such as postoperative pain and
      migraine, schizophrenia, major depression, chronic mental stress, and others. In
      arthritis, abnormalities of glucose homeostasis were described in 1920; and in
      1950 combined glucose and insulin tests unmistakably demonstrated IR. The
      phenomenon is now described in rheumatoid arthritis, systemic lupus
      erythematosus, ankylosing spondylitis, polymyalgia rheumatica, and others. In
      chronic inflammatory diseases, cytokine-neutralizing strategies normalize insulin
      sensitivity. This paper delineates that IR is either based on inflammatory
      factors (activation of the immune/ repair system) or on the brain (mental
      activation via stress axes). Due to the selfishness of the immune system and the
      selfishness of the brain, both can induce IR independent of each other.
      Consequently, the immune system can block the brain (for example, by sickness
      behavior) and the brain can block the immune system (for example, stress-induced
      immune system alterations). Based on considerations of evolutionary medicine, it
      is discussed that obesity per se is not a disease. Obesity-related IR depends on
      provoking factors from either the immune system or the brain. Chronic
      inflammation and/or stress axis activation are thus needed for obesity-related
      IR. Due to redundant pathways in stimulating IR, a simple one factor-neutralizing
      strategy might help in chronic inflammatory diseases (inflammation is the key),
      but not in obesity-related IR. The new considerations towards IR are interrelated
      to the published theories of IR (thrifty genotype, thrifty phenotype, and
      others). 

PMID- 25608960
TI  - Media coverage of violence against women in India: a systematic study of a high
      profile rape case.
AB  - BACKGROUND: On December 16, 2012 a 23 year old female was gang-raped on a bus in
      Delhi. We systematically reviewed professional online media sources used to
      inform the timing, breadth of coverage, opinions and consistency in the depiction
      of events surrounding the gang-rape. METHODS: We searched two news databases
      (LexisNexis Academic and Factivia) and individual newspapers for English-language
      published media reports covering the gang-rape. Two reviewers screened the media
      reports and extracted data regarding the time, location and content of each
      report. Results were summarized qualitatively. RESULTS: We identified 534
      published media reports. Of these, 351 met our eligibility criteria. Based on a
      time chart, the total number of reports published increased steadily through
      December, but plateaued to a steady rate of articles per day by the first week of
      January. Content analysis revealed significant discrepancies between various
      media reports. From the 57 articles which discussed opinions about the victim,
      56% applauded her bravery, 40% discussed outrage over the events and 11%
      discussed cases of victim-blaming. CONCLUSIONS: The global media response of the
      December 16th gang-rape in India resulted in highly inconsistent depiction of the
      events. These findings suggest that although the spread of information through
      media is fast, it has major limitations.

PMID- 25608962
TI  - Alcohol and drug misuse, abuse, and dependence in women veterans.
AB  - We conducted a systematic literature review on substance misuse, abuse, and
      dependence in women veterans, including National Guard/reserve members. We
      identified 837 articles published between 1980 and 2013. Of 56 included studies,
      32 reported rates of alcohol misuse, binge drinking, or other unhealthy alcohol
      use not meeting diagnostic criteria for abuse or dependence, and 33 reported
      rates of drug misuse or diagnosed alcohol or drug use disorders. Rates ranged
      from 4% to 37% for alcohol misuse and from 7% to 25% for binge drinking; among
      Veterans Health Administration (VA) health-care system outpatients, rates ranged
      from 3% to 16% for substance use disorder. Studies comparing women veterans and
      civilians reported no clear differences in binge or heavy drinking. Substance
      misuse rates were generally lower among women veterans than men veterans.
      Substance misuse was associated with higher rates of trauma, psychiatric and
      medical conditions, and increased mortality and suicide rates. Most studies
      included only VA patients, and many used only VA medical record data; therefore,
      the reported substance misuse rates likely do not reflect true prevalence. Rates
      also varied by assessment method, source of data, and the subgroups studied.
      Further efforts to develop epidemiologically valid prevalence estimates are
      needed to capture the true health burden of substance misuse in women veterans,
      particularly those not using VA care. 

PMID- 25608961
TI  - Host-specific transcriptomic pattern of Trichoderma virens during interaction
      with maize or tomato roots.
AB  - BACKGROUND: Members of the fungal genus Trichoderma directly antagonize soil
      borne fungal pathogens, and an increasing number of species are studied for their
      potential in biocontrol of plant pathogens in agriculture. Some species also
      colonize plant roots, promoting systemic resistance. The Trichoderma-root
      interaction is hosted by a wide range of plant species, including monocots and
      dicots. RESULTS: To test the hypothesis that gene expression by the fungal
      partner in this beneficial interaction is modulated by the plant, Trichoderma
      virens was co-cultured with maize or tomato in a hydroponic system allowing
      interaction with the roots. The transcriptomes for T. virens alone were compared
      with fungus-inoculated tomato or maize roots by hybridization on microarrays of
      11645 unique oligonucleotides designed from the predicted protein-coding gene
      models. Transcript levels of 210 genes were modulated by interaction with roots.
      Almost all were up-regulated. Glycoside hydrolases and transporters were highly
      represented among transcripts induced by co-culture with roots. Of the genes up
      regulated on either or both host plants, 35 differed significantly in their
      expression levels between maize and tomato. Ten of these were expressed higher in
      the fungus in co-culture with tomato roots than with maize. Average transcript
      levels for these genes ranged from 1.9 fold higher on tomato than on maize to
      60.9 fold for the most tomato-specific gene. The other 25 host-specific
      transcripts were expressed more strongly in co-culture with maize than with
      tomato. Average transcript levels for these genes were 2.5 to 196 fold higher on
      maize than on tomato. CONCLUSIONS: Based on the relevant role of Trichoderma
      virens as a biological control agent this study provides a better knowledge of
      its crosstalk with plants in a host-specific manner. The differentially expressed
      genes encode proteins belonging to several functional classes including enzymes,
      transporters and small secreted proteins. Among them, glycoside hydrolases and
      transporters are highlighted by their abundance and suggest an important factor
      in the metabolism of host cell walls during colonization of the outer root
      layers. Host-specific gene expression may contribute to the ability of T. virens
      to colonize the roots of a wide range of plant species.

PMID- 25608963
TI  - Ewing sarcoma of the liver with multilocular cystic mass formation: a case
      report.
AB  - BACKGROUND: Ewing sarcoma is a rare tumor that occurs commonly in the long bones
      of children or adolescents that can also arise in soft tissues including the
      extremities, retroperitoneum, chest wall, and rarely in the liver as primary
      sites. We report a case of Ewing sarcoma arising primarily in the liver and, to
      our knowledge, this is the fourth reported case of Ewing sarcoma occurring in the
      liver. CASE PRESENTATION: A 27-year-old Japanese woman was admitted with sudden
      onset right upper abdominal pain. Clinical examination revealed a multilocular
      cystic mass consisting of thickened, irregular septa and nodal walls in the right
      hepatic lobe. Ultrasound-guided aspiration biopsy of the liver mass showed
      clusters of small atypical round cells and the clinical preoperative diagnosis
      was mucinous cystadenoma of the liver. The patient underwent an extended right
      hepatectomy and histopathological findings revealed sheet-like proliferation of
      small- to medium-sized round cells. Tumor cells were positive for periodic acid
      Schiff reaction and immunoreactive for glycoprotein C99 and gene NKX2.2, as well
      as the neuroendocrine markers, CD56 and synaptophysin. EWS-FLI-1 fusion
      transcript type 1 was detected by reverse transcriptase polymerase chain
      reaction. Pathological and molecular analysis confirmed the diagnosis of Ewing
      sarcoma arising primarily in the liver and the patient received adjuvant systemic
      chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating
      with ifosfamide and etoposide. We found no evidence of recurrence 15 months after
      completing chemotherapy. CONCLUSION: We present an extremely rare case of Ewing
      sarcoma arising primarily in the liver. To our knowledge, this is the fourth
      reported case of Ewing sarcoma occurring in the liver, and the first case with a
      multilocular cystic liver mass. Imaging examinations of the other three reported
      cases showed solid tumors and a diffuse enlarged liver without mass lesion.
      Clinicians should consider the possibility of Ewing sarcoma in young patients
      with a multilocular cystic mass with thick and/or irregular cyst walls in the
      liver.

PMID- 25608965
TI  - L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative
      stress and mitochondrial dysfunction in mouse offspring.
AB  - Maternal smoking is associated with metabolic disorders, renal underdevelopment,
      and a predisposition to chronic kidney disease in offspring, yet the underlying
      mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6
      wk premating and during gestation and lactation, we showed that maternal smoke
      exposure induced glucose intolerance, renal underdevelopment, inflammation, and
      albuminuria in male offspring. This was associated with increased renal oxidative
      stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we
      demonstrated that dietary supplementation of l-carnitine, an amino acid shown to
      increase antioxidant defenses and mitochondrial function in numerous diseases, in
      smoke-exposed mothers during pregnancy and lactation significantly reversed the
      detrimental maternal impacts on kidney pathology in these male offspring. It
      increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and
      normalized levels of mitochondrial preprotein translocases of the outer membrane,
      and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after
      intrauterine cigarette smoke exposure. These findings support the hypothesis that
      oxidative stress and mitochondrial dysfunction are closely linked to the adverse
      effects of maternal smoking on male offspring renal pathology. The results of our
      study suggest that l-carnitine administration in cigarette smoke-exposed mothers
      mitigates these deleterious renal consequences. 

PMID- 25608964
TI  - Estrogen directly and specifically downregulates NaPi-IIa through the activation
      of both estrogen receptor isoforms (ERalpha and ERbeta) in rat kidney proximal
      tubule.
AB  - We have previously demonstrated that estrogen (E2) downregulates phosphate
      transporter NaPi-IIa and causes phosphaturia and hypophosphatemia in
      ovariectomized rats. In the present study, we examined whether E2 directly
      targets NaPi-IIa in the proximal tubule (PT) and studied the respective roles of
      estrogen receptor isoforms (ERalpha and ERbeta) in the downregulation of NaPi-IIa
      using both in vivo and an in vitro expression systems. We found that estrogen
      specifically downregulates NaPi-IIa but not NaPi-IIc or Pit2 in the kidney
      cortex. Proximal tubules incubated in a "shake" suspension with E2 for 24 h
      exhibited a dose-dependent decrease in NaPi-IIa protein abundance. Results from
      OVX rats treated with specific agonists for either ERalpha [4,4',4";-(4-propyl
      [1H]-pyrazole-1,3,5-triyl) trisphenol, PPT] or ERbeta [4,4',4"-(4-propyl-[1H]
      pyrazole-1,3,5-triyl) trisphenol, DPN] or both (PPT + DPN), indicated that only
      the latter caused a sharp downregulation of NaPi-IIa, along with significant
      phosphaturia and hypophosphatemia. Lastly, heterologous expression studies
      demonstrated that estrogen downregulated NaPi-IIa only in U20S cells expressing
      both ERalpha and ERbeta, but not in cells expressing either receptor alone. In
      conclusion, these studies demonstrate that rat PT cells express both ERalpha and
      ERbeta and that E2 induces phosphaturia by directly and specifically targeting
      NaPi-IIa in the PT cells. This effect is mediated via a mechanism involving
      coactivation of both ERalpha and ERbeta, which likely form a functional
      heterodimer complex in the rat kidney proximal tubule. 

PMID- 25608966
TI  - Identification and function of adenosine A3 receptor in afferent arterioles.
AB  - Adenosine plays an important role in regulation of renal microcirculation. All
      receptors of adenosine, A1, A2A, A2B, and A3, have been found in the kidney.
      However, little is known about the location and function of the A3 receptor in
      the kidney. The present study determined the expression and role of A3 receptors
      in mediating the afferent arteriole (Af-Art) response and studied the interaction
      of A3 receptors with angiotensin II (ANG II), A1 and A2 receptors on the Af-Art.
      We found that the A3 receptor expressed in microdissected isolated Af-Art and the
      mRNA levels of A3 receptor were 59% of A1. In the isolated microperfused Af-Art,
      A3 receptor agonist IB-MECA did not have a constrictive effect. Activation of A3
      receptor dilated the preconstricted Af-Art by norepinephrine and blunted the
      vasoconstrictive effect of both adenosine A1 receptor activation and ANG II on
      the Af-Art, respectively. Selective A2 receptor antagonist (both A2A and A2B) had
      no effect on A3 receptor agonist-induced vasodilation, indicating that the
      dilatory effect of A3 receptor activation is not mediated by activation of A2
      receptor. We conclude that the A3 receptor is expressed in the Af-Art, and
      activation of the A3 receptor dilates the Af-Art. 

PMID- 25608968
TI  - Infection and immunity on a chip: a compartmentalised microfluidic platform to
      monitor immune cell behaviour in real time.
AB  - Cells respond to their environments and self-organise into multicellular
      assemblies with dedicated functions. The migratory and homing response of cells
      to soluble ligands can be studied by using different techniques, but for real
      time studies of complex multicellular self-organisation, novel and simpler
      systems are required. We fabricated a flexible open access microsystem and tested
      the design by studying cell recruitment from an immune cell reservoir towards an
      infectious compartment. The two compartments were connected by a network of
      bifurcated microchannels allowing diffusion of signalling molecules and migration
      of cells. Bacterial filters were incorporated in the design to prevent bacteria
      and activated cells from entering the network, permitting migration only from the
      recruitment reservoir. The fabricated microsystem allows real-time continuous
      monitoring of cellular decision-making based on biologically produced gradients
      of cytokines and chemokines. It is a valuable tool for studying cellular
      migration and self-organisation in relation to infections, autoimmunity, cancer,
      stem cell homing, and tissue and wound repair. 

PMID- 25608967
TI  - Glycogen synthase kinase 3alpha regulates urine concentrating mechanism in mice.
AB  - In mammals, glycogen synthase kinase (GSK)3 comprises GSK3alpha and GSK3beta
      isoforms. GSK3beta has been shown to play a role in the ability of kidneys to
      concentrate urine by regulating vasopressin-mediated water permeability of
      collecting ducts, whereas the role of GSK3alpha has yet to be discerned. To
      investigate the role of GSK3alpha in urine concentration, we compared GSK3alpha
      knockout (GSK3alphaKO) mice with wild-type (WT) littermates. Under normal
      conditions, GSK3alphaKO mice had higher water intake and urine output.
      GSK3alphaKO mice also showed reduced urine osmolality and aquaporin-2 levels but
      higher urinary vasopressin. When water deprived, they failed to concentrate their
      urine to the same level as WT littermates. The addition of 1-desamino-8-d
      arginine vasopressin to isolated inner medullary collecting ducts increased the
      cAMP response in WT mice, but this response was reduced in GSK3alphaKO mice,
      suggesting reduced responsiveness to vasopressin. Gene silencing of GSK3alpha in
      mpkCCD cells also reduced forskolin-induced aquaporin-2 expression. When treated
      with LiCl, an isoform nonselective inhibitor of GSK3 and known inducer of
      polyuria, WT mice developed significant polyuria within 6 days. However, in
      GSK3alphaKO mice, the polyuric response was markedly reduced. This study
      demonstrates, for the first time, that GSK3alpha could play a crucial role in
      renal urine concentration and suggest that GSK3alpha might be one of the initial
      targets of Li(+) in LiCl-induced nephrogenic diabetes insipidus. 

PMID- 25608969
TI  - Commentary on 'Protective effect of focal adhesion kinase against skeletal muscle
      reperfusion injury after acute limb ischemia'.

PMID- 25608971
TI  - Noteworthy articles in 2014 for cardiothoracic anesthesiologists.
AB  - In 2014, cardiothoracic anesthesiology again generated high-quality scientific
      work published in highly regarded journals. Our specialty continues to make
      significant strides in the creation and implementation of protocols to improve
      outcomes in our patients, which undoubtedly contribute to a safer hospital
      environment for patients and employees alike. Another theme that stirred a lot of
      interest in the past year is the search for patient-centered treatment plans.
      Even though we are still some time away from truly personalized medicine, our
      specialty starts to ask and answer exciting questions: Would we treat patient A
      any different from patient B if their genetic profiles were easily accessible?
      Could individualized treatment choices influence our patients' immediate and long
      term outcomes? For this review, we selected a sample of relevant contributions to
      the field of cardiothoracic anesthesiology in 2014 with potential impact on our
      clinical routine. 

PMID- 25608970
TI  - Quantification of cell identity from single-cell gene expression profiles.
AB  - The definition of cell identity is a central problem in biology. While single
      cell RNA-seq provides a wealth of information regarding cell states, better
      methods are needed to map their identity, especially during developmental
      transitions. Here, we use repositories of cell type-specific transcriptomes to
      quantify identities from single-cell RNA-seq profiles, accurately classifying
      cells from Arabidopsis root tips and human glioblastoma tumors. We apply our
      approach to single cells captured from regenerating roots following tip excision.
      Our technique exposes a previously uncharacterized transient collapse of identity
      distant from the injury site, demonstrating the biological relevance of a
      quantitative cell identity index. 

PMID- 25608972
TI  - An adolescent with an altered state of mind.

PMID- 25608973
TI  - Pamidronate affects the mandibular cortex of children with osteogenesis
      imperfecta.
AB  - We hypothesized that mandibular cortical width (MCW) is smaller in children with
      osteogenesis imperfecta (OI) than in healthy children and that pamidronate can
      improve the cortical mandibular thickness. The aim of this study was to assess
      changes in the MCW on dental panoramic radiographs (DPRs) of children with normal
      bone mineral density (BMD) and with OI. We also compared the MCW of children with
      different types of OI regarding the number of pamidronate cycles and age at the
      beginning of treatment. MCW measurements were retrospectively obtained from 197
      DPRs of 66 children with OI types I, III, and IV who were in treatment with a
      comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The
      control group had 92 DPRs from normal BMD children. Factorial analysis of
      variance was used to compare MCW measurements among different age groups and
      between sexes and also to compare MCW measurements of children with different
      types of OI among different pamidronate cycles and age at the beginning of
      treatment. No significant differences in results were found between male and
      female subjects in both OI and healthy children, so they were evaluated
      altogether (P > 0.05). There was an increase of MCW values related to aging in
      all normal BMD and OI children but on a smaller scale in children with OI types I
      and III. Children with OI presented lower mean MCW values than did children with
      normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the
      number of pamidronate cycles necessary to achieve mean MCW values equivalent to
      those of healthy children. The thinning of the mandibular cortex depended on the
      number of pamidronate cycles, the type of OI, and the age at the beginning of
      treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment
      outcomes in patients with OI. 

PMID- 25608974
TI  - How rural and urban parents describe convenience in the context of school-based
      influenza vaccination: a qualitative study.
AB  - BACKGROUND: Seasonal influenza vaccine uptake among school-age children has been
      low, particularly among rural children, even in jurisdictions in Canada where
      this immunization is publicly funded. Providing this vaccination at school may be
      convenient for parents and might contribute to increased vaccine uptake,
      particularly among rural children. We explore the construct of convenience as an
      advantage of school based influenza vaccination. We also explore for rural urban
      differences in this construct. METHODS: Participants were parents of school-aged
      children from Alberta, Canada. We qualitatively analyzed focus group data from
      rural parents using a thematic template that emerged from prior work with urban
      parents. Both groups of parents had participated in focus groups to explore their
      perspectives on the acceptability of adding an annual influenza immunization to
      the immunization program that is currently delivered in Alberta schools. Data
      from within the theme of 'convenience' from both rural and urban parents were
      then further explored for sub-themes within convenience. RESULTS: Data were
      obtained from nine rural and nine urban focus groups. The template of themes that
      had arisen from prior analysis of the urban data applied to the rural data.
      Convenience was a third level theme under Advantages. Five fourth level themes
      emerged from within convenience. Four of the five sub-themes were common to both
      rural and urban participants: reduction of parental burden to schedule, reduction
      in parental lost time, decrease in parental stress and increase in physical
      access points for influenza immunization. The fifth subtheme, increases temporal
      access to influenza immunization, emerged uniquely from the rural data.
      CONCLUSIONS: Both rural and urban parents perceived that convenience would be an
      advantage of adding an annual influenza immunization to the vaccinations
      currently given to Alberta children at school. Improving temporal access to such
      immunization may be a more relevant aspect of convenience to rural than to urban
      parents.

PMID- 25608976
TI  - Endoscopic ultrasound - fine needle aspiration of 2-deoxy-2-[18F] fluoro-D
      glucose avid lymph nodes seen on positron emission tomography- computed
      tomography -what looks like cancer may not always be so.
AB  - BACKGROUND: Patients suffering from malignancies often undergo serial positron
      emission tomography - computed tomography (PET-CT) scans, using 2-deoxy-2-[18F]
      fluoro-D-glucose (FDG) for diagnosis and follow up. This principle may also be
      applied to benign conditions as inflammatory cells take up increased amounts of
      FDG as well. The aim of our study was to retrospectively review the cytological
      diagnoses made at EUS-FNA of FDG-avid PET-CT lesions in patients with a history
      of cancer and to determine whether the cause of FDG-avidity was neoplastic or
      benign. METHODS: We used the endoscopy database to extract clinical information
      on all patients with malignancies who underwent EUS-FNA to obtain tissue from FDG
      avid nodes seen on PET-CT at our institution from 2009 - 2012. All patients who
      were referred for EUS-FNA after their scans were included. Those who had
      contraindications to endoscopic procedures were excluded. RESULTS: The most
      common location of positive lymph nodes was the subcarinal region (46%). A
      definitive diagnosis was obtained in 87.8% cases, of which 51.2% had a diagnosis
      of malignancy confirmed on cytology, while 36.5% were benign. Out of these, 29%
      had granulomatous inflammation. In 12.2% of cases no definitive diagnosis was
      obtained. CONCLUSION: Our results show that great caution should be exercised
      when evaluating FDG-avid PET-CT nodes in patients with known malignant disease,
      as a significant proportion of these lesions may be benign, particularly in
      geographic locations with a high background prevalence of granulomatous
      inflammation.

PMID- 25608975
TI  - Opposing regulation of endolysosomal pathways by long-acting nanoformulated
      antiretroviral therapy and HIV-1 in human macrophages.
AB  - BACKGROUND: Long-acting nanoformulated antiretroviral therapy (nanoART) is
      designed to improve patient regimen adherence, reduce systemic drug toxicities,
      and facilitate clearance of human immunodeficiency virus type one (HIV-1)
      infection. While nanoART establishes drug depots within recycling and late
      monocyte-macrophage endosomes, whether or not this provides a strategic advantage
      towards viral elimination has not been elucidated. RESULTS: We applied
      quantitative SWATH-MS proteomics and cell profiling to nanoparticle atazanavir
      (nanoATV)-treated and HIV-1 infected human monocyte-derived macrophages (MDM).
      Native ATV and uninfected cells served as controls. Both HIV-1 and nanoATV
      engaged endolysosomal trafficking for assembly and depot formation, respectively.
      Notably, the pathways were deregulated in opposing manners by the virus and the
      nanoATV, likely by viral clearance. Paired-sample z-scores, of the proteomic data
      sets, showed up- and down- regulation of Rab-linked endolysosomal proteins.
      NanoART and native ATV treated uninfected cells showed limited effects. The data
      was confirmed by Western blot. DAVID and KEGG bioinformatics analyses of
      proteomic data showed relationships between secretory, mobility and phagocytic
      cell functions and virus and particle trafficking. CONCLUSIONS: We posit that
      modulation of endolysosomal pathways by antiretroviral nanoparticles provides a
      strategic path to combat HIV infection.

PMID- 25608977
TI  - Medicinal use of wild fauna by mestizo communities living near San Guillermo
      Biosphere Reserve (San Juan, Argentina).
AB  - BACKGROUND: Wild and domestic animals and their by-products are important
      ingredients in the preparation of curative, protective and preventive medicines.
      Despite the medicinal use of animals worldwide, this topic has received less
      attention than the use of medicinal plants. This study assessed the medicinal use
      of animals by mestizo communities living near San Guillermo MaB Reserve by
      addressing the following questions: What animal species and body parts are used?
      What ailments or diseases are treated with remedies from these species? To what
      extent do mestizo people use animals as a source of medicine? Is the use related
      to people's age? METHODS: We conducted semi-structured interviews with 171
      inhabitants (15-93 years old) of four villages close to the Reserve: Tudcum,
      Angualasto, Maliman and Colanguil. We calculated the informant consensus factor
      and fidelity level to test homogeneity of knowledge and to know the importance of
      different medicinal uses for a given species. RESULTS: The medicinal use of
      animals was reported by 57% of the surveyed people. Seven species were mentioned:
      Rhea pennata, Lama guanicoe, Puma concolor, Pseudalopex sp., Lama vicugna, Lepus
      europaeus and Conepatus chinga. Several body parts were used: fat, leg, bezoar
      stone, stomach, feather, meat, blood, feces, wool, and liver. The fat of R.
      pennata was the most frequently used animal part, followed by the bezoar stone
      and the leg of L. guanicoe. Animals were used to treat 22 ailments, with
      respiratory and nervous system disorders being the most frequently treated
      diseases with a high degree of consensus. Old people used animals as remedies
      more frequently than young residents, showing some differences among villages.
      CONCLUSIONS: A low number of animal species was mentioned as used for medicinal
      purposes, which could be explained by the perception of strong control related
      the legislation that bans hunting and the erosion of traditional knowledge
      produced by mestizaje. However, the presence of a traditional medicine is deeply
      rooted in the community culture. Management strategy for protected areas should
      focus not only on the conservation and sustainability of biological resources,
      but also on the ancestral knowledge of local communities, such as the medicinal
      use of animals.

PMID- 25608978
TI  - Molecular cloning, expression, and evolution analysis of type II CHI gene from
      peanut (Arachis hypogaea L.).
AB  - Chalcone isomerase (CHI) plays critical roles in plant secondary metabolism,
      which is important for the interaction between plants and the environment. CHI
      genes are widely studied in various higher plants. However, little information
      about CHI genes is available in peanut. Based on conservation of CHI gene family,
      we cloned the peanut type II CHI gene (AhCHI II) cDNA and genome sequence. The
      amino acid sequence of peanut CHI II was highly homologous to type II CHI from
      other plant species. qRT-PCR results showed that peanut CHI II is mainly
      expressed in roots; however, peanut CHI I is mainly expressed in tissues with
      high content of anthocyanin. Gene duplication and gene cluster analysis indicated
      that CHI II was derived from CHI I 65 million years ago approximately. Our gene
      structure analysis results are not in agreement with the previous hypothesis that
      CHI II was derived from CHI I by the insertion of an intron into the first exon.
      Moreover, no positive selection pressure was found in CHIs, while, 32.1 % of
      sites were under neutral selection, which may lead to mutation accumulation and
      fixation during great changes of environment.

PMID- 25608979
TI  - A fungating spica.
AB  - Developmental dysplasia of the hip (DDH) is a common paediatric orthopaedic
      problem. There are various options for treatment dependent on the age and
      presentation. In closed and open reduction of DDH, we use a hip spica cast for
      immobilisation after the procedure. We present an unusual case of fungal growth
      on a hip spica. A 7-month-old girl presented to our institution with clusters of
      yellowish-white outgrowths resembling mushrooms from her spica. To the best of
      our knowledge, this is the first reported case of fungal growth on a hip spica
      following DDH treatment. It is of utmost importance to be aware of any growth on
      a hip spica, as this requires a prompt change of spica to avoid further
      complications. We recommend that the integrity of the spica and the skin be
      checked at regular intervals in patients with a hip spica. 

PMID- 25608980
TI  - Osteomyelitis, discitis, epidural and psoas abscess secondary to Salmonella
      enterica in a man with diabetes mellitus and newly diagnosed alpha-thalassaemia
      trait.
AB  - We report the case of a 65-year-old man with type 2 diabetes mellitus and alpha
      thalassaemia trait. Investigations for relapsing and remitting fever found
      vertebral osteomyelitis, discitis and epidural and psoas abscess secondary to
      Salmonella enterica. 

PMID- 25608981
TI  - Necrotising pneumonia and bronchiectasis in a previously healthy 30-year-old man.
AB  - We present a case of a previously healthy 30-year-old man who presented with a
      necrotising pneumonia and bronchiectasis. His infectious workup revealed a
      Staphylococcus aureus pneumonia. Since bronchiectasis and necrotising pneumonia
      are unusual findings in an otherwise healthy person, further investigation was
      pursued. His workup revealed non-classic cystic fibrosis (CF) and allergic
      bronchopulmonary aspergillosis (ABPA). This case discusses the differential
      diagnosis of bronchiectasis, the diagnosis and treatment of ABPA, and the role of
      CF mutations in the pathogenesis of ABPA. 

PMID- 25608982
TI  - Myocardial infarction associated with eosinophilia and plasma extravasation at
      multiple sites. A variant of Kounis syndrome.
AB  - Myocardial infarction occurring during the course of type I hypersensitivity
      constitutes Kounis syndrome. We report a case of a 38-year-old man who presented
      with anterior ST elevation myocardial infarction and peripheral blood
      eosinophilia. He had rhinitis and malaise for several days prior to presentation.
      There was no urticarial rash or pruritus to suggest hypersensitivity. Coronary
      angiogram revealed only mild plaque disease. Blood investigations revealed
      moderate eosinophilia and elevated IgE levels. CT of the thorax revealed fluid
      extravasation at multiple sites. Screening for a possible secondary cause for
      eosinophilia revealed hypersensitivity to multiple antigens. A diagnosis of
      Kounis syndrome was made. Within days of starting steroids and antihistamines,
      the patient's eosinophil count returned to normal with improvement of clinical
      picture. This case differs from classical Kounis syndrome as there was no acute
      allergic reaction (except atopic rhinitis). Fluid extravasation at multiple sites
      has not been described in previous cases. 

PMID- 25608983
TI  - Association between chronic disease and catastrophic health expenditure in Korea.
AB  - BACKGROUND: The prevalence and economic burden of chronic diseases are increasing
      worldwide. Nevertheless, little information is available on catastrophic health
      expenditures (CHE) associated with chronic diseases in Korea. This study explored
      the burden of household out-of-pocket health expenditures among the Korean
      population for different chronic diseases. METHODS: This study was conducted
      utilizing data collected from the 7,006 households that participated in the Korea
      Health Panel Survey (KHPS) in 2008. The effect of CHE in relation to type of
      chronic disease was assessed via multiple logistic regression analysis. RESULTS:
      Roughly 3.5% of the participating households experienced CHE. As opposed to
      households headed by females and middle-aged individuals (40-59 years), those of
      low economic status, elderly households, and households with a member who
      suffered from a chronic disease were more likely to experience CHE. According to
      type of chronic condition, households with a member who suffered from
      cerebrovascular disease, diabetes, or chronic kidney disease were at a
      significantly higher risk of experiencing CHE. CONCLUSION: Although Korea has
      greatly expanded its health insurance coverage, financial protection against CHE
      remains a concern. Policy-makers need to focus on expanding benefits according to
      the economic burden of individual chronic conditions.

PMID- 25608984
TI  - Topical Allium ampeloprasum subsp Iranicum (Leek) extract cream in patients with
      symptomatic hemorrhoids: a pilot randomized and controlled clinical trial.
AB  - Allium ampeloprasum subsp iranicum (Leek) has been traditionally used in
      antihemorrhoidal topical herbal formulations. This study aimed to evaluate its
      safety and efficacy in a pilot randomized controlled clinical trial. Twenty
      patients with symptomatic hemorrhoids were randomly allocated to receive the
      topical leek extract cream or standard antihemorrhoid cream for 3 weeks. The
      patients were evaluated before and after the intervention in terms of pain,
      defecation discomfort, bleeding severity, anal itching severity, and reported
      adverse events. A significant decrease was observed in the grade of bleeding
      severity and defecation discomfort in both the leek and antihemorrhoid cream
      groups after the intervention, while no significant change was observed in pain
      scores. There was no significant difference between the leek and antihemorrhoid
      cream groups with regard to mean changes in outcome measures. This pilot study
      showed that the topical use of leek cream can be as effective as a standard
      antihemorrhoid cream. 

PMID- 25608986
TI  - [Guideline of cervical ripening and labor induction during the third trimester
      pregnancy].

PMID- 25608985
TI  - Brain dynamics of visual attention during anticipation and encoding of threat-
      and safe-cues in spider-phobic individuals.
AB  - This study systematically investigated the sensitivity of the phobic attention
      system by measuring event-related potentials (ERPs) in spider-phobic and non
      phobic volunteers in a context where spider and neutral pictures were presented
      (phobic threat condition) and in contexts where no phobic but unpleasant and
      neutral or only neutral pictures were displayed (phobia-irrelevant conditions).
      In a between-group study, participants were assigned to phobia-irrelevant
      conditions either before or after the exposure to spider pictures (pre-exposure
      vs post-exposure participants). Additionally, each picture was preceded by a
      fixation cross presented in one of three different colors that were informative
      about the category of an upcoming picture. In the phobic threat condition, spider
      phobic participants showed a larger P1 than controls for all pictures and signal
      cues. Moreover, individuals with spider phobia who were sensitized by the
      exposure to phobic stimuli (i.e. post-exposure participants) responded with an
      increased P1 also in phobia-irrelevant conditions. In contrast, no group
      differences between spider-phobic and non-phobic individuals were observed in the
      P1-amplitudes during viewing of phobia-irrelevant stimuli in the pre-exposure
      group. In addition, cues signaling neutral pictures elicited decreased stimulus
      preceding negativity (SPN) compared with cues signaling emotional pictures.
      Moreover, emotional pictures and cues signaling emotional pictures evoked larger
      early posterior negativity (EPN) and late positive potential (LPP) than neutral
      stimuli. Spider phobics showed greater selective attention effects than controls
      for phobia-relevant pictures (increased EPN and LPP) and cues (increased LPP and
      SPN). Increased sensitization of the attention system observed in spider-phobic
      individuals might facilitate fear conditioning and promote generalization of fear
      playing an important role in the maintenance of anxiety disorders. 

PMID- 25608987
TI  - [Clinical effect of fetoscopic laser occlusion of chorioangiopagous vessels for
      twin-twin transfusion syndrome: experience of an center from China].
AB  - OBJECTIVE: To study the clinical effect of fetoscopic laser occlusion of
      chorioangiopagous vessels (FLOC) in treating twin to twin transfusion syndrome.
      METHODS: The clinical data of 44 consecutive cases of twin to twin transfusion
      syndrome (TTTS)who had FLOC in the Department of Obstetrics and Gynaecology of
      Peking University Third Hospital were reviewed and analyzed for perioperative
      complications, perinatal outcomes and fetal survival rate. RESULTS: (1) PATIENT
      CHARACTERISTICS: the mean maternal age was (29+/-4) years, the median gestational
      age at TTTS being primarily diagnosed was 20.4 weeks, the median gestational age
      at FLOC was 21.2 weeks. According to the Quintero staging system, there were 9
      cases had stages progressed before the operation. (2) FLOC parameter and
      intraoperative complications: 44 cases all could tolerate the operation; there
      was 1 case of placenta vascular rupture in the operation, no fetal body injury by
      laser or placental abruption. 3 cases underwent cervical cerclage following FLOC.
      The average operation time of 41 cases alone with FLOC was (60.1+/-15.1) minutes.
      (3) Postoperative complications: the rate of intrauterine fetal death was 15%
      (13/88), the rate of intrauterine growth restriction after FLOC was 5% (4/88),
      the rate of membranes rupture less than 28 weeks was 16% (7/44), the rate of TAPS
      after FLOC was 5% (2/44), the rate of membrane sepration after FLOC was 5%
      (2/44). (4) Perinatal outcome and survival rate: there were 25 patients after
      FLOC had delivered in the perinatal period. The average gestational age of
      delivery was (33.5+/-2.7) weeks. The donor fetuses survival rate was 88% (22/25),
      the recipient fetuses survival rate was 100% (25/25). The birth weight of donor
      fetuses was significantly less than that of recipient fetuses (1 631g vs 2 071 g,
      P = 0.016). From Quintero staging I to IV, the rate that 44 cases of TTTS had
      entered the perinatal period was 4/7, 11/14, 7/19, 3/4; both twins survival rates
      were 4/7, 10/14, 5/19, 3/4; all the fetal survival rate was 8/14, 75% (21/28),
      32% (12/38), 6/8, respectively. (5) Compared the early stage (I+II) with the
      advanced stage (III+IV), the rates that 44 cases of TTTS had entered the
      perinatal period (71% vs 44%) and that both twins survived (67% vs 35%) had no
      statistically significance. The rate that all the fetus survived in the early
      stage was significantly (69% vs 39%) more than that in the advanced stage. (6)
      All the cases of neoborn were followed up till 1 month postpartum, the donor
      fetuses and the recipient fetuses had 12 and 5 cases of cardiac abnormalities
      respectively, each had 1 case of neonatal death and 2 cases of neonatal white
      matter damage. CONCLUSIONS: FLOC for TTTS is associated with a better survival
      rate. Quintero staging probably does not effectively predict the fetal diagnosis
      of TTTS after FLOC. When TTTS diagnosed, the sooner FLOC given, the better fetal
      prognosis had.

PMID- 25608988
TI  - [Clinical value of genome-wide high resolution chromosomal microarray analysis in
      etiological study of fetuses with congenital heart defects].
AB  - OBJECTIVE: To explore the clinical value of genome-wide high resolution
      chromosomal microarray analysis (CMA) in etiological study of fetuses with
      congenital heart disease (CHD) diagnosed by fetal echocardiography. METHODS: A
      total of 176 fetuses diagnosed CHD by fetal echocardiography were analyzed, and
      invasive prenatal diagnosis was performed at Guangzhou Women and Children's
      Medical Center from January 2012 to January 2014. Among them, 158 fetuses were
      proved to have normal karyotype, and 88 fetuses (50.0%, 88/176) underwent CMA
      testing. The parental blood specimens were also collected for assisting the
      diagnosis of variants of uncertain clinical significance (VOUS). The 88 fetuses
      were divided into two groups: isolated CHD (n = 68) and CHD with extra-cardiac
      structural abnormalities (n = 20). The phenotypes of the two groups were
      subclassified. Copy number variations (CNV) were classified as benign CNV,
      pathogenic CNV (pCNV) or VOUS. RESULTS: (1) 58 fetuses (66%, 58/88) were with
      simple CHD and 30 fetuses were with complicated CHD (34%, 30/88). In the 45
      fetuses with isolated and simple CHD, the pCNV detection rate was 11% (5/45). In
      the 23 fetuses with isolated and complicated CHD, the pCNV detection rate was 17%
      (4/23). In the 13 fetuses with simple CHD and extra-cardiac structural
      abnormalities, the pCNV detection rate was 5/13. In the 7 fetuses with
      complicated CHD and extra-cardiac structural abnormalities, the pCNV detection
      rate was 0. (2) The total detection rate for pCNV detection was 16% (14/88) in
      the 88 fetuses. The pCNV detection rates for isolated CHD and CHD with extra
      cardiac structural abnormalities were 13% (9/68) and 25% (5/20), respectively (P
      > 0.05). The pCNV detection rates for simple and complicated CHD were 17% (10/58)
      and 13% (4/30), respectively (P > 0.05). (3) Eighteen fetuses (10.2%, 18/176) had
      abnormal karyotype results. (4) CMA test was performed in 88 fetuses. CNV
      detected in 8 fetuses were classified as VOUS initially. After parental
      microarray analysis, CNV in 5 fetuses were inherited and interpreted as benign.
      CNV in the other 3 fetuses (3%, 3/88) were remained unknown significance. CNV in
      14 fetuses (16% ) were interpreted as pCNV. CONCLUSIONS: In fetuses with CHD and
      normal karyotype, the application of CMA could increase the detection rate of
      pCNV. Genome-wide CMA could be used as a regular tool in the prenatal diagnosis
      of fetuses with CHD and normal karyotype. This technology may benefit evaluation
      of fetal prognosis in prenatal genetic counselling.

PMID- 25608989
TI  - [Study of reconstruction of digital three-dimensional model of normal human
      placental vascular network based on MRI data in vitro].
AB  - OBJECTIVE: To investigate the reconstruction of digital three-dimensional (3D)
      model of normal human placental vascular network based on MRI data in vitro.
      METHODS: Six full term placentas were collected, casted with modified self-curing
      denture base resin and scanned by T1 e-THRIVE high resolution magnetic resonance
      imaging. MRI images were imported into Mimics 14.0 software for 3D
      reconstruction, and the 3D model was compared with placental vascular casting
      model. RESULTS: (1) The placental vascular network could be obtained on MR 2D
      images. The 3D model were reconstructed successfully, which showed clear,
      realistic images. The 3D model could be zoomed and revolved from any direction to
      observe the branches of arteries and veins. (2) The umbilical vein and 2
      umbilical arteries could be seen in the 3D model. In the root of the umbilical
      cord, the umbilical vein divided into 5-7 branches. While the 2 umbilical
      arteries anatomoses to form blood sinus and then devided into sub-branches. All
      the peripheral vessels ended in chorionic plate with abundant sub-branches. (3)
      When compared with the casting of placental arterial-venous vascular network, the
      morphology, structure, angle and trend of vessels in 3D model was consistent with
      the casting network. CONCLUSIONS: Reconstruction of digital 3D model of normal
      human placental vascular network based on MRI in vitro is a new and promising
      method for the study of placental vasculature. It has better vascular exposure,
      free rotation, radiation-free. It provides a promising base for the study of
      placental vasculature in vivo in the future.

PMID- 25608990
TI  - [Comparision of in vitro maturation applied in PCOS and non-PCOS patients undergo
      stimulated and unstimulated protocols].
AB  - OBJECTIVE: To compare the laboratory and clinical results between unstimulated in
      vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in
      polycystic ovarian syndrome (PCOS) and non-PCOS patients. METHODS: We divided 591
      IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from
      Jan. 2008 to Dec. 2013 into 4 groups: group A1B1, PCOS patients underwent
      unstimulated IVM protocol, 240 cycles; group A1B2, PCOS patients underwent IVM
      converted from conventional stimulated IVF protocol, 153 cycles; group A2B1, non
      PCOS patients underwent unstimutlated IVM protocol, 103 cycles; group A2B2, non
      PCOS patient underwent IVM converted from conventional stimulated IVF protocol,
      95 cycles. Multiple linear regression method and binary logistic regression
      method were used to assess the influence of PCOS and protocols for IVM on
      laboratory and clinical outcomes. RESULTS: The mean number of oocytes retrieved
      was positively related with PCOS [partial regression coefficient (B) = 3.37, P <
      0.01]. The maturation rate of oocytes was positively related with hCG-prime prior
      to oocyte aspiration (B = 0.05, P = 0.010). High-quality embryo rate was
      positively related with PCOS and IVM converted from IVF (B = 0.08, P = 0.010; B =
      0.09, P = 0.001), as well as implantation rate related with them (B = 0.07, P =
      0.010; B = 0.10, P < 0.01). PCOS and IVM converted from IVF improved hCG positive
      (hCG>10 U/L) rate (OR = 1.636, 95%CI: 1.113-2.204, P < 0.05; OR = 1.861, 95%CI:
      1.307-2.649, P < 0.05) and the clinical pregnancy rate (OR = 1.507, 95%CI: 1.041
      2.240, P < 0.05; OR = 1.881, 95%CI: 1.312-2.696, P < 0.05). IVM converted from
      IVF protocol decreased the spontaneous abortion rate (OR = 0.490, 95%CI: 0.245
      0.978, P < 0.05). Multiple gestation rate and ectopic pregnancy rate were not
      affected by PCOS condition and protocol used (P > 0.05). CONCLUSIONS: PCOS and
      IVM converted from IVF protocol improved the high-quality embryo rate,
      implantation rate, hCG positive rate and clinical pregnancy rate. IVM converted
      from IVF protocol reduced the spontaneous abortion rate. PCOS patients may be
      more suitable for the IVM treatment. No matter PCOS or non-PCOS patients, IVM
      converted from IVF protocol had better pregnancy outcome than that of
      unstimulated cycle.

PMID- 25608991
TI  - [Relationship between letrozole administration during the luteal phase after
      oocyte retrieval and the early-stage ovarian hyperstimulation syndrome
      oocurrence].
AB  - OBJECTIVE: To investigate the effect of letrozole in decreasing the early-stage
      ovarian hyperstimulation syndrome (OHSS) occurrence during the luteal phase for
      patients of OHSS high-risk after oocyte retrieval. METHODS: A total of 176 high
      risk OHSS patients were randomly divided into two groups after oocyte retrieval.
      Patients in experiment group (n = 86) received 5 mg letrozole per day from the
      retrieval day and last for 5 days. Others in control group (n = 90) received
      placebo. The serum concentration of FSH, LH, estradiol (E2), progesterone (P) and
      vascular endothelial growth factor (VEGF) from the day of hCG injection to days
      after injection (5 days, 8 days, 10 days) were measured. And the incidence of
      moderate and severe OHSS was observed. RESULTS: The concentration of E2 on the
      indicated days (5 days, 8 days, 10 days after hCG injection) in experiment group
      and control group were (5 727+/-2 089) versus (11 826+/-4 281) pmol/L, (1 613+/
      879) versus (7 925+/-3 507) pmol/L, (193+/- 90) versus (1 628+/-888) pmol/L; the
      concentration of VEGF on the indicated days in the two groups were (80+/-14)
      versus (108+/-19) ng/L, (66+/-11) versus (126+/-14) ng/L, (48+/-7) versus (148+/
      14) ng/L; the concentration of E2 and VEGF were lower than those in control group
      (all P < 0.01). The FSH concentration in experiment group were (2.1+/-1.1) and
      (3.5+/-1.3) U/L on the day of fifth and eighth day after hCG injection, which
      were significantly higher than (0.7+/-0.3) and (0.7+/-0.4) U/L in control group
      (P < 0.05); the LH concentration in experiment group were (0.26+/-0.19) and
      (0.72+/-0.60) U/L on the day of fifth and eighth day after hCG injection, which
      were significantly higher than (0.11+/-0.03) and (0.14+/-0.08) U/L in control
      group (P < 0.05). The incidence of moderate and severe OHSS was signicantly
      decreased after letrozole treatment compared with control group [2% (2/86) versus
      12% (11/90), P < 0.05]. CONCLUSION: Administration of 5 mg/d letrozole for 5 days
      during the luteal phase can reduce the E2 and VEGF levels for the high-risk OHSS
      patients who needed cryopreserve all embryos, and also reduce the occurrence of
      early OHSS.

PMID- 25608992
TI  - [Clinical value of MRI in cesarean scar pregnancy].
AB  - OBJECTIVE: To explore the clinical value of MRI in diagnosing and treating
      cesarean scar pregnancy (CSP). METHODS: A retrospective analysis was conducted on
      the clinical manifestations of 54 patients diagnosed with CSP between January
      2009 to January 2013 in Peking University Third Hospital. Based on the patients'
      MRI image and other clinical datas, we did transvaginal operation on patients
      with CSP1, and transvaginal combined with abdominal operations on patients with
      CSP2. The intraoperative blood loss, operation time, postoperative hospital stay,
      and the length of time required for of serum hCG dropping to normal of the
      patients were analyzed. RESULTS: The average age of the 54 patients was (34+/-5)
      years and the average duration of gestation was (56+/-16) days, all patients'
      vital sign were stable, the hCG level was 23-142 962 U/L before treatment. Twelve
      patients were diagnosed with CSP1 by MRI, and 5 of them had focus of 1-2 cm in
      diameter, the 5 patients' serum hCG level was 436-1 159 U/L and 23-32 days after
      drug administration, their hCG level returned to normal; the other 7 patients had
      focus of 2.0-4.4 cm in diameter, and their hCG level was 2 218-63 446 U/L, lesion
      resection was done on the 7 patients by hysteroscope or under B-ultrasound
      monitor. Forty-two patients were diagnosed with CSP2, and their focus were 1.0
      7.1 cm in diameter, and serum hCG level were 23-142 962 U/L. We did bilateral
      uterine artery occlusion by laparoscope or laparotomy during operation for 22
      patients or bilateral uterine artery embolization (UAE) before operation for 20
      patients, then we did lesion resections. The blood loss during operation of CSP1
      or CSP 2 was 50.1, 267.2 ml; operation time was 30, 128 minutes; postoperative
      hospital stay was 4.6, 6.7 days; their serum hCG returned to normal 13-30 days
      after the surgery. All the 54 patients' uterus were and the patients undergoing
      operations were all cured without the second operation. CONCLUSION: MRI is an
      effective method to conduct clinical treatment in CSP.

PMID- 25608993
TI  - [Association between single nucleotide polymorphism of rs2252673 of INSR gene and
      polycystic ovarian syndrome].
AB  - OBJECTIVE: This study is designed to determine whether an association exists
      between single nucleotide polymorphism (SNP) variant rs2252673 of insulin
      receptor (INSR) gene and polycystic ovarian syndrome (PCOS) in Han Chinese in
      order to identify INSR as a genetic susceptibility factor for PCOS. METHODS: A
      total of 224 women with PCOS, 192 controls and 672 participants consisting of 224
      trios (mother, father and offspring with PCOS) were recruited from the Hospital
      for Reproductive Medicine Affiliated to Shandong University, from July 2007 to
      April 2013. Genomic DNA was extracted according to the manufacturer's protocol.
      SNP rs2252673 of INSR gene was amplified by PCR and then sequenced on an
      automated sequencer. Moreover, clinical and metabolic features of the patients
      with PCOS were compared according to the genotypes. The subjects were divided
      into twot groups according to body mass index (BMI), and then the results were
      compared between two groups. And the transmitted disequilibrium test (TDT) was
      applied for data analysis. RESULTS: (1) There were three kinds of genotype of CC,
      CG and GG. Genotype frequencies of rs2252673 were 8.0%, 38.8%, 53.1% and 14.6%,
      42.2%, 43.2% in the PCOS group and the control group, respectively. The allele
      frequencies of C and G were 27.5%, 72.5% and 35.7%, 64.3% in the PCOS group and
      the control group, respectively. There were statistical differences in genotype
      frequencies and allele frequencies between two groups (all P < 0.05 ). (2)No
      significant differences were observed in the different genotype according to
      clinical and metabolic characteristics of women with PCOS(P > 0.05). But when
      merging the genotype CG and GG, carriers of the CG and GG genotypes in women with
      PCOS were slightly associated with total cholesterol (TC) levels (t = 2.072, P =
      0.048) and lower high-density lipoprotein (HDL) levels (t = 2.274, P = 0.026).
      Although statistical significance was not achieved, there was an increased
      tendency in fasting blood glucose (FBG) and fasting insulin (FINS) levels in CG
      and GG genotypes in PCOS cases.(3)Between the obesity and the non-obesity with
      PCOS, there was no statistical significance in the genotype and allele
      frequencies (chi(2) = 0.054, P = 0.974; chi(2) = 0.022, P = 0.883 ). (4) The
      results of families based analysis shown that genotype distribution of the SNP
      rs2252673 was in Hardy-Weinberg equilibrium (P > 0.05). After the TDT, the G
      allele in SNP rs2252673 was over transmitted in families (transmitted:non
      transmitted = 120:88; chi(2) = 4.923, P = 0.027). There was a transmitted
      disequilibrium in rs2252673, which implies the association of INSR and PCOS were
      independent of population stratification. CONCLUSIONS: There were a association
      between the SNP variant rs2252673 of INSR gene and the susceptibility to PCOS in
      Han Chinese women, which was independently of body mass index. The carrier of G
      allele frequency of rs2252673 may have higher risk of PCOS.

PMID- 25608994
TI  - [Estradiol activates MAPK signaling pathway by estrogen induced VEGF and bFGF in
      endometrial cancer cells].
AB  - OBJECTIVE: To explore the effects of mitogen-activated protein kinase (MAPK)
      pathway by estradiol induced vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) in endometrial cancer Ishikawa cells. METHODS:
      The experiments were divided into 4 groups: E2 group (Ishikawa cells treated with
      1 umol/L estradiol for 30 minutes); inhibitor group: including Ishikawa cells
      treated with 10 umol/L Bibf1120 (Bibf1120 group), or treated with 2.5 umol/L
      Ponatinib (Ponatinib group), or treated with 10 umol/L U0126 (U0126 group) for 60
      minutes; inhibitor + E2 group: including Ishikawa cells treated with 10 umol/L
      Bibf1120 (Bibf1120 + E2 group), or treated with 2.5 umol/L Ponatinib (Ponatinib +
      E2 group), or treated with 10 umol/L U0126 (U0126 + E2 group) for 60 minutes
      following incubation with 1 umol/L estradiol for 30 minutes;control group: only
      adding the culture medium without serum DMEM. (1) Western blot analysis was used
      to detect phosphorylation extracellular signal-regulated kinase 1/2(p-ERK1/2)
      protein expression with stimulation in different concentrations of estradiol
      (0.01,0.1, 1, 10, 100 umol/L). (2)Quantitative fluorescent reverse transcription
      (qRT)-PCR and western blot analysis was used to test the level of mRNA and
      protein of VEGF, bFGF, MAPK kinase 1/2 (MEK1/2), extracellular signal-regulated
      kinase 1/2 (ERK1/2), p-ERK1/2 and phosphorylation MEK1/2(p-MEK1/2). Flow
      cytometry were used to examine the cell cycle, and transwell chamber assay were
      used to detect the cell migration in different groups. RESULTS: The expression of
      the p-ERK1/2 protein at 0.01,0.1, 1, 10, 100 umol/L were 0.16+/-0.03, 0.10+/
      0.03, 0.41+/-0.04, 0.19+/-0.03, 0.19+/-0.03, there were significantly higher than
      that in control group (0.05+/-0.00, P < 0.05), and which was more obvious at the
      concentration of 1 umol/L estradiol. The expression level of VEGF, bFGF mRNA and
      protein in E2 group were higher than those in the control group(P < 0.05). VEGF
      mRNA and protein in Bibf1120+E2 group were higher than those in E2 group. The
      expression of MEK1/2, ERK1/2 mRNA protein in E2 group were higher than those in
      control group (P < 0.05). The expression of MEK1/2, ERK1/2 mRNA or p-MEK1/2, p
      ERK1/2 protein in Bibf1120 + E2 group, Ponatinib+E2 group or U0126+E2 group were
      lower than those in E2 group (all P < 0.05). Percentage of G1 phase ([53.6+/
      3.2)%] and S phase ([ 29.2+/-4.2)%] in E2 group was significantly different with
      those in control group respectively(P < 0.05). Percentage of G1 phase [(66.8+/
      2.6)%, (63.1+/-2.6)% and (63.3+/-0.4)%] and S phase [(25.4+/-1.9)%, (25.0+/-3.8)%
      and (23.8+/-0.5)%] in U0126+E2 group, Bibf1120+E2 group or Ponatinib +E2 group
      was also significantly different with those in control group(all P < 0.05);
      percentage of G1 phase and S phase in U0126+E2 group was significant difference
      with those in Bibf1120+E2 group or ponatinib+E2 group (P < 0.05). The number of
      cell colony in E2 group (110+/-17) was more than those in control group(65+/
      8);the number of cell colony in U0126+E2 group (28+/-4), Bibf1120+E2 group (38+/
      5) or Ponatinib+E2 group (42+/-6) were significant different with those in E2
      group (P < 0.05), the number of cell colony in U0126+E2 group was significant
      difference with those in Bibf1120+E2 group or Ponatinib+E2 group (all P < 0.05).
      The results shown that the abilities of proliferation and cell migration were
      significantly increased in cells after estradiol stimulation. CONCLUSION:
      Estradiol inducing the production of VEGF and bFGF could activate MAPK pathway
      through ER-independent manner, further promote development.

PMID- 25608995
TI  - [Effects of metformin on the estrogen-induced proliferation and the expression of
      ER in human endometrial cancer cells].
AB  - OBJECTIVE: To assess the effects of metformin on estrogen-induced proliferation
      of human endometrial cancer cell lines and investigate whether metformin could
      regulate the expression of ER and estrogen-dependent proliferative genes.
      METHODS: Human endometrial cancer cell lines Ishikawa and HEC-1A underwent
      treatment with metformin at various concentrations (0.5, 1, 5, 10, 15, 20, 25 and
      30 mmol/L) for different durations (24, 48 and 72 hours), followed by assessment
      of cell proliferation by methyl thiazolyl tetrazolium (MTT) assay. Ishikawa and
      HEC-1A cells were exposed to 17beta-estradiol (1*10(-6) mol/L) alone or in
      combination with metformin (5 mmol/L) for 24 hours. Cell proliferation was
      assessed by 5-bromo-2-deoxyuridine (BrdU) assay. Twenty-four hours after
      metformin treatment at the concentrations of 1, 5 and 15 mmol/L, the expression
      levels of estrogen-dependent proliferative genes c-fos and c-myc were determined
      by real-time quantitative fluorescent PCR (real-time FQ-PCR). Western blot
      analysis was performed to assess the effects of metformin on the expressions of
      estrogen receptors. RESULTS: As revealed by MTT assay, at different time points
      of metformin treatment at different concentrations, the proliferation rates of
      both cell lines were inhibited in a dose-dependent and time-dependent manner
      between metformin groups and the control group (P < 0.05). BrdU assay showed that
      the proliferation rate of Ishikawa and HEC-1A cells exposed to 17beta-estradiol
      (1*10(-6) mol/L) in combination with metformin (5 mmol/L) was (62+/-7)% and (72+/
      6)%, respectively, while that in 17beta-estradiol groups was (124+/-16)% and
      (109+/-5)%, respectively, with significantly statistical differences (P < 0.01).
      By real-time FQ-PCR tested, the expression levels of c-fos and c-myc in both cell
      lines gradually declined subsequent to metformin treatment at different
      concentrations (1, 5 and 15 mmol/L). As compared with the control group, the c
      myc and c-fos expressions in both cell lines in metformin groups had significant
      differences (P < 0.05) except for the c-myc expression of the concentration of 1
      mmol/L in HEC-1A cell line (P = 0.074). Western blot analyses showed that with
      the increasing concentrations of metformin, the ERa expression was markedly down
      regulated, while ERbeta expression was up-regulated in the metformin group at the
      concentrations of 5 mmol/L and 15 mmol/L, compared to those at the control group,
      there were significant differences between them, respectively (all P < 0.01).
      CONCLUSION: Metformin could inhibit estrogen-mediated proliferation of human
      endometrial cancer cells, which might be correlated with its regulation of the
      expressions of estrogen receptors and estrogen-dependent proliferative genes.

PMID- 25608996
TI  - Activation of NOD1 by DAP contributes to myocardial ischemia/reperfusion injury
      via multiple signaling pathways.
AB  - NOD1 is a member of nucleotide-binding oligomerization domain-like receptors
      family that participates in many inflammatory processes. Previous studies
      demonstrated that NOD1 plays an important role in inflammatory cardiovascular
      diseases. However, its role in myocardial ischemia/reperfusion (I/R) injury
      remains unknown. The present study investigate whether NOD1 is involved in the
      pathogenesis of mouse myocardial I/R injury and the underlying mechanisms.
      Administration of NOD1 ligand (DAP) significantly enhanced myocardial I/R injury,
      as demonstrated by increased infarct size, the number of TUNEL-positive nuclei,
      caspase-3 activity, the infiltration of Mac-2- and IL-6-positive cells as
      compared with untreated heart or cardiomyocytes after I/R injury. In contrast,
      knockdown of NOD1 by siRNA markedly attenuated mimetic I/R induced cardiomyocyte
      apoptosis in vitro, indicating that NOD1 enhanced myocardial I/R injury partially
      through direct heart effects. These effects were partially associated with
      activation of JNK, p38 MAPK and NF-kappaB signaling pathways. Taken together,
      these results provide the first evidence that activation of intracellular sensor
      NOD1 enhances myocardial I/R injury and may provide novel therapeutic target for
      ameliorating the ischemic heart diseases. 

PMID- 25608997
TI  - [Obesity: an increasing problem].

PMID- 25608998
TI  - [Ischemic renal disease and renal artery stenosis].
AB  - Severe renal artery stenosis may cause renovascular hypertension; in case of
      bilateral narrowing or in a stenotic solitary or transplant kidney, renal
      insufficiency (ischemic renal disease) or rarely pulmonary flash edema may occur.
      In most cases arteriosclerotic disease is the underlying cause; less prevalent
      are the various manifestations of fibromuscular disease. Renal artery stenosis
      may be treated by revasularization, using either percutaneous (balloon
      angioplasty, stenting) or rarely open surgical procedures, both with excellent
      primary patency rates. However, randomized trials of renal artery angioplasty or
      stenting in patients with arteriosclerotic lesions have failed to demonstrate a
      longer-term benefit with regard to hypertension control and renal dysfunction
      over medical management alone. Careful patient selection is essential to maximize
      the potential benefit (e.g., in patients with refractory hypertension,
      progressive renal failure or recurrent pulmonary flash edema). 

PMID- 25608999
TI  - [Therapy-resistant hypertension].
AB  - BACKGROUND: Therapy-resistant hypertension is commonly encountered in daily
      practice. It is present when the therapeutic goal is not achieved after trying at
      least three antihypertensives from different groups with adequate doses and
      including a diuretic. Between 10 and 20% of patients are affected and their
      prognosis is poor. Thus, intensive strategies are required to achieve
      normotension. DIAGNOSIS: An exact diagnosis is essential. Pseudoresistance needs
      to be excluded in addition to secondary hypertension and sleep apnea syndrome.
      The most common cause of pseudoresistance is incorrect blood pressure
      measurement, false estimation of the real blood pressure level, lack of
      compliance, unhealthy lifestyle, and drug interactions. Therapeutic resistance
      should not be diagnosed without 24 h ambulatory blood pressure measurement. This
      significantly reduces the total number of "resistant" patients. THERAPY:
      Successful control of blood pressure is achieved in the majority of patients by
      taking advantage of all possible therapy options. Treatment with 4-6
      antihypertensive drugs is justified because of the improvement of cardiovascular
      prognosis. However, prerequisite is the absence of undesirable side effects which
      is the most important condition for adequate and reliable patient compliance.
      Only in the case of failure of the above therapy options can invasive procedures-
      renal denervation and baroreflex activation therapy--be applied as they are still
      experimental. Successful management of patients with resistant hypertension is
      only possible with intensive and time-consuming physician-patient relationships.

PMID- 25609000
TI  - New methodology for quantifying the effects of perennials on their patch
      productivity in semi-arid environments.
AB  - The correlations between perennials and the herbaceous productivity in patches
      occupied by them were previously studied and several descriptive models were
      defined. Yet these studies focused on either single or several species without
      analyzing higher numbers and ranking their effects. Here we describe a handy
      analytical methodology which allows separating the effects of each perennial
      species on herbaceous productivity at its respective patches from those of the
      others in a given area, even in case of complex patches containing several
      species. The described methodology also allows analysts to correlate the effect
      of perennials to their patch sizes and the respective herbaceous biomass.
      Additional mathematical analysis presented here succeeded in differentiating
      between the perennial species stand-alone presence effect on the herbaceous
      productivity and that attributed to the canopy size. In addition, the effects of
      location along the slope and its rockiness outlines were studied. As a case
      study, we chose representative sloped shrubland with rockiness outlines, located
      in Yattir farm, Northern Negev, Israel. Based on the described analyses we found
      that the species with the highest positive effects on the herbaceous productivity
      were Echinops polyceras, Echium angustifolium, and Salvia lanigera. Contradictory
      effects were observed in case of Thymelea hirsute, Anchusa ramosus, and Noaea
      mucronata. Collectively, the presented methodology could be an important
      management tool for monitoring the herbaceous biomass amounts in a given
      shrubland. 

PMID- 25609001
TI  - Correction: Studies towards asymmetric synthesis of 4(S)-11
      dihydroxydocosahexaenoic acid (diHDHA) featuring cross-coupling of chiral
      stannane under mild conditions.
AB  - Correction for 'Studies towards asymmetric synthesis of 4(S)-11
      dihydroxydocosahexaenoic acid (diHDHA) featuring cross-coupling of chiral
      stannane under mild conditions' by Rui Wang et al., Org. Biomol. Chem., 2015,
      DOI: 10.1039/c4ob02324b. 

PMID- 25609002
TI  - Hepatic vein obstruction is the most common type of hepatic venous outflow
      obstruction regardless of socioeconomic status.
AB  - BACKGROUND: Data regarding role of socioeconomic status (SES) as etiology and
      site of involvement of veins in hepatic venous outflow tract obstruction (HVOTO)
      is scarce and only described from Nepal. We prospectively evaluated the role of
      SES in patients with HVOTO. METHODS: 70 consecutive patients (41 females; mean
      age 29, range 3-65 years) with HVOTO were studied. Their clinical history,
      socioeconomic factors (income, education, and occupation), birth history, dietary
      factors, living standards, baseline characteristics, liver function, and clinical
      parameters were evaluated. RESULTS: Of the 70 patients analyzed, 48 (68.5%) had
      hepatic vein (HV) obstruction, 7 (10%) had isolated inferior vena cava (IVC)
      obstruction, and 15 (21.5%) had combined HV and IVC obstruction. Of the 10
      patients belonging to the upper SES, 7 had isolated HV obstruction, and 3 had
      combined IVC and HV obstruction; no patient had isolated IVC obstruction. Of the
      60 patients belonging to the lower SES, 41(68.4%) had HV obstruction, and 19
      (31.6%) had IVC involvement with (n=12) or without (n=7) HV involvement. HV/IVC
      involvement did not correlate with setting of delivery (hospital vs. home), birth
      weight, birth complications, immunization in childhood, ventilation in house,
      water storage facilities, history of diarrhea, or diet. Patients with HVOTO
      living in a mud house had IVC obstruction more commonly than HV (6/22 vs. 4/48;
      P=0.04). CONCLUSION: Isolated hepatic vein obstruction is the most common site of
      obstruction in patients with HVOTO in India, even among those belonging to low
      SES. Patients with HVOTO living in a mud house have IVC obstruction more
      commonly. Other socioeconomic factors studied do not appear to correlate with the
      site of obstruction.

PMID- 25609003
TI  - Bilastine: an environmental risk assessment.
AB  - CONTEXT: Bilastine is a new oral selective, non-sedating histamine H1 antagonist
      for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. The
      European Medicines Agency requires an Environmental Risk Assessment (ERA) for all
      novel medicines for human use. OBJECTIVE: To calculate the bilastine predicted
      environmental concentration in surface water (PECsw; phase I ERA), and to
      determine the effects of bilastine on aquatic systems (phase II [tier A]).
      MATERIALS AND METHODS: Bilastine PECsw was calculated using the maximum daily
      dosage (20 mg), assuming that all administered bilastine was released into the
      aquatic environment. A persistence, bioaccumulation and toxicity assessment was
      conducted using the log Kow from the molecular structure. In phase II (tier A), a
      ready biodegradability test was performed, and bilastine's potential toxicity to
      various aquatic and sediment-dwelling micro-organisms was evaluated. RESULTS:
      Bilastine PECSW was calculated as 0.1 MUg L(-1), and the compound was not readily
      biodegradable. Bilastine had no significant effects on Chironomus riparius
      midges, or on the respiration rate of activated sludge. For green algae, the
      bilastine no observed effect concentration (NOEC) was 22 mg L(-1); bilastine had
      no effect on zebra fish development, or on the reproduction rate of daphnids.
      DISCUSSION: Bilastine NOEC values against zebra fish, algae, daphnids, and
      aerobic organisms in activated sludge were at least 130 000-fold greater than the
      calculated PECSW value. CONCLUSION: No environmental concerns exist from
      bilastine use in patients with allergic rhinoconjunctivitis or urticaria.

PMID- 25609004
TI  - Protective effects of silymarin on epirubicin-induced mucosal barrier injury of
      the gastrointestinal tract.
AB  - Mucositis is a serious disorder of the gastrointestinal tract that results from
      cancer chemotherapy. We investigated the protective effects of silymarin on
      epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical
      activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together
      with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine
      and colon were evaluated. Our results indicated stronger expression for cyt P450
      in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense
      drug detoxification. Bax immunopositivity was intense in the absorptive
      enterocytes and lamina connective cells of the small intestine, surface
      epithelial cells of the stomach and also in the colonic epithelium and lamina
      concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin
      induced gastrointestinal damage was verified by a goblet cell count and
      morphology analysis on histopathological sections stained for mucins. In all
      analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of
      silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with
      control. p53 expression was found in all analyzed tissues and decreased by high
      dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the
      Epi groups for all analyzed tissues was almost suppressed at 100 mg/kg Sy co
      treatment. Histological aspect and goblet cell count were restored at a highest
      dose of Sy for both small and large intestine. In conclusion, our findings
      suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity
      and was effective in reducing the severity indicators of gastrointestinal
      mucositis in mice. 

PMID- 25609005
TI  - Shared rhytidectomy continued to lateral canthoplasty in a Mastiff with excessive
      facial folding and macroblepharon.
AB  - A 3.5-year-old male Neapolitan Mastiff was presented with an obstructed visual
      axis because of excessive facial skin folds, brow droop, macroblepharon, upper
      eyelid entropion and lower ectropion-entropion. To address these major defects a
      technique was performed which combines rhytidectomy with shortening of the
      palpebral fissure and stabilization of the lateral canthus. Postoperatively the
      dog showed an unobstructed visual axis with comfortable and symmetrical eyes. 

PMID- 25609007
TI  - Dose-dense biweekly docetaxel combined with 5-fluorouracil as first-line
      treatment in advanced gastric cancer: a phase II trial.
AB  - This study evaluated the efficacy, safety and impact on quality of life (QoL) of
      a dose-dense biweekly regimen of docetaxel and 5-fluorouracil in first-line
      treatment of advanced gastric cancer (AGC). Eligible patients received docetaxel
      60 mg/m(2) and 5-fluorouracil (400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-h
      infusion), fortnightly. Prophylactic use of G-CSF was adopted in all patients.
      The primary end point was response rate (RR). Secondary end points were
      progression-free survival (PFS), overall survival (OS), toxicity and QoL. Thirty
      nine patients with a median age of 55 (28-80) were included. The RR was 51.3 %.
      Median PFS and OS were 6.7 and 14.0 months, respectively. The most common adverse
      events (all grades) were anemia (34, 87.2 %), fatigue (29, 74.4 %), neutropenia
      (26, 66.7 %), nail change (19, 48.7 %) and liver dysfunction (15, 38.5 %). In QoL
      analysis, improvements were obtained in seven scales, whereas drops were seen in
      three scales. Common Grade 3/4 toxicities included anemia (28.2 %), liver
      dysfunction (7.7 %) and fatigue (7.7 %). This novel regimen is a promising option
      for AGC, showing high RR, improvement on QoL and acceptable toxicity. 

PMID- 25609006
TI  - Intraperitoneal administration of cisplatin plus bevacizumab for the management
      of malignant ascites in ovarian epithelial cancer: results of a phase III
      clinical trial.
AB  - Bevacizumab is a humanized antihuman VEGF-A monoclonal antibody. This study aims
      to evaluate the efficacy and safety of intraperitoneal administration of
      cisplatin plus bevacizumab (Avastin) in the management of malignant ascites in
      ovarian epithelial cancer. Fifty-eight ovarian epithelial cancer patients with
      malignant ascites were randomly assigned to receive either intraperitoneal
      administration of cisplatin only (control group, n = 27, cisplatin: 40 mg/m(2)
      every 2 weeks, for 6 weeks) or cisplatin plus bevacizumab (study group, n = 31,
      cisplatin: 40 mg/m(2), bevacizumab: 300 mg, every 2 weeks for 6 weeks). All
      patients regularly received TC regimen (paclitaxel 135 mg/m(2) d1 + carboplatin
      AUC 5 d1) every 3 weeks. The outcome, quality of life (QoL) and adverse effect of
      the treatment were analyzed, and VEGF and CA-125 level in ascites were detected
      by ELISA. After treatment with cisplatin plus bevacizumab, VEGF level in ascites
      was significantly decreased compared to baseline (P < 0.05). Meanwhile, ascites
      VEGF level of study group was significantly lower than that of control group (P <
      0.05). The overall response rate (ORR) of study group was significantly higher
      than that of control group (ORR 90.32 vs. 59.26 %, P < 0.05). QoL improvement
      rate of study group was also significantly higher than that of control group
      (93.55 vs. 48.15 %, P < 0.05). All patients were well tolerated, and no serious
      adverse effect occurred. Intraperitoneal administration of cisplatin plus
      bevacizumab is effective and safe for the management of malignant ascites in
      ovarian epithelial cancer. 

PMID- 25609008
TI  - In vitro expansion of corneal endothelial cells on biomimetic substrates.
AB  - Corneal endothelial (CE) cells do not divide in vivo, leading to edema, corneal
      clouding and vision loss when the density drops below a critical level. The
      endothelium can be replaced by transplanting allogeneic tissue; however, access
      to donated tissue is limited worldwide resulting in critical need for new sources
      of corneal grafts. In vitro expansion of CE cells is a potential solution, but is
      challenging due to limited proliferation and loss of phenotype in vitro via
      endothelial to mesenchymal transformation (EMT) and senescence. We hypothesized
      that a bioengineered substrate recapitulating chemo-mechanical properties of
      Descemet's membrane would improve the in vitro expansion of CE cells while
      maintaining phenotype. Results show that bovine CE cells cultured on a
      polydimethylsiloxane surface with elastic modulus of 50 kPa and collagen IV
      coating achieved >3000-fold expansion. Cells grew in higher-density monolayers
      with polygonal morphology and ZO-1 localization at cell-cell junctions in
      contrast to control cells on polystyrene that lost these phenotypic markers
      coupled with increased alpha-smooth muscle actin expression and fibronectin
      fibril assembly. In total, these results demonstrate that a biomimetic substrate
      presenting native basement membrane ECM proteins and mechanical environment may
      be a key element in bioengineering functional CE layers for potential therapeutic
      applications. 

PMID- 25609009
TI  - Proteasome assembly from 15S precursors involves major conformational changes and
      recycling of the Pba1-Pba2 chaperone.
AB  - The chaperones Ump1 and Pba1-Pba2 promote efficient biogenesis of 20S proteasome
      core particles from its subunits via 15S intermediates containing alpha and beta
      subunits, except beta7. Here we elucidate the structural role of these chaperones
      in late steps of core particle biogenesis using biochemical, electron microscopy,
      cross-linking and mass spectrometry analyses. In 15S precursor complexes, Ump1 is
      largely unstructured, lining the inner cavity of the complex along the interface
      between alpha and beta subunits. The alpha and beta subunits form loosely packed
      rings with a wider alpha ring opening than in the 20S core particle, allowing for
      the Pba1-Pba2 heterodimer to be partially embedded in the central alpha ring
      cavity. During biogenesis, the heterodimer is expelled from the alpha ring by a
      restructuring event that organizes the beta ring and leads to tightening of the
      alpha ring opening. In this way, the Pba1-Pba2 chaperone is recycled for a new
      round of proteasome assembly. 

PMID- 25609010
TI  - Exosome delivered anticancer drugs across the blood-brain barrier for brain
      cancer therapy in Danio rerio.
AB  - PURPOSE: The blood-brain barrier (BBB) essentially restricts therapeutic drugs
      from entering into the brain. This study tests the hypothesis that brain
      endothelial cell derived exosomes can deliver anticancer drug across the BBB for
      the treatment of brain cancer in a zebrafish (Danio rerio) model. MATERIALS AND
      METHODS: Four types of exosomes were isolated from brain cell culture media and
      characterized by particle size, morphology, total protein, and transmembrane
      protein markers. Transport mechanism, cell uptake, and cytotoxicity of optimized
      exosome delivery system were tested. Brain distribution of exosome delivered
      anticancer drugs was evaluated using transgenic zebrafish TG (fli1: GFP) embryos
      and efficacies of optimized formations were examined in a xenotransplanted
      zebrafish model of brain cancer model. RESULTS: Four exosomes in 30-100 diameters
      showed different morphologies and exosomes derived from brain endothelial cells
      expressed more CD63 tetraspanins transmembrane proteins. Optimized exosomes
      increased the uptake of fluorescent marker via receptor mediated endocytosis and
      cytotoxicity of anticancer drugs in cancer cells. Images of the zebrafish showed
      exosome delivered anticancer drugs crossed the BBB and entered into the brain. In
      the brain cancer model, exosome delivered anticancer drugs significantly
      decreased fluorescent intensity of xenotransplanted cancer cells and tumor growth
      marker. CONCLUSIONS: Brain endothelial cell derived exosomes could be potentially
      used as a carrier for brain delivery of anticancer drug for the treatment of
      brain cancer.

PMID- 25609011
TI  - The Influence of Chitosan on the Oral Bioavailability of Acyclovir--a Comparative
      Bioavailability Study in Humans.
AB  - PURPOSE: The effects of chitosan hydrochloride on the oral absorption of
      acyclovir in humans were studied to confirm the absorption enhancing effects
      reported for in vitro and rat studies, respectively. METHODS: A controlled, open
      label, randomized, 3-phase study was conducted in 12 healthy human volunteers.
      Zovirax 200 mg dispersible tablets co-administered with doses of 400 and 1000 mg
      chitosan HCl were compared with Zovirax only. RESULTS: The expected increased
      absorption of acyclovir was not observed. On the contrary, mean area under the
      plasma concentration-time curve (AUC0-12 h) and maximal plasma concentration
      (Cmax) decreased following concomitant chitosan intake (1402 versus 1017 and
      982.0 ng ? h/ml and 373 versus 208 and 235 ng/ml, respectively). In addition,
      Tmax increased significantly in presence of 1000 mg of chitosan from 1 to 2 h.
      CONCLUSIONS: The results of this study in human volunteers did not confirm an
      absorption enhancing effect of chitosan. Reference values were comparable to
      literature data, whereas addition of chitosan resulted in significant opposite
      effects on Cmax, Tmax and AUC. Additional studies are needed to investigate the
      cause of the discrepancy. The observed variability and complex potential
      interactions may complicate the use of chitosan HCl in oral pharmaceutical
      formulations.

PMID- 25609012
TI  - Thermosensitive progesterone hydrogel: a safe and effective new formulation for
      vaginal application.
AB  - PURPOSE: The safe and functional delivery of progesterone through the vaginal
      route remains an unmet clinical need. The purpose of this work is to prepare a
      new progesterone (P4) gel for vaginal application using a thermosensitive
      mucoadhesive polymer, glycol chitin (GC). METHOD: Thermogelling, mucoadhesive,
      mechanical, and viscoelastic properties of GC and the new formulation were
      evaluated using rheometry. In vitro release profile and the bioactivity of P4
      were determined using vaginal fluid simulant (VFS) pH 4.2, and PR-reporter gene
      assay, respectively. In vitro safety of the formulations was tested using
      (VK2/E6E7) vaginal epithelial cell line and Lactobacillus Crispatus. Finally, in
      vivo safety and the efficacy of this formulation were evaluated using an
      endometrial hypoplasia mouse model. RESULTS: Results shows the aqueous solution
      of 5%; (w/v) GC loaded with 0.1%; (w/v) P4 prepared in pH 4.2, (GC-P4), forms a
      thermosensitive mucoadhesive hydrogel and can maintain stable physical properties
      at 37  degrees C. GC-P4 gel release 50% of P4 in 4 h after exposure to VFS, and
      no significant decrease in % viability of VK2/E6E7 or Lactobacillus was found
      after exposure to 5% GC or GC-P4. GC-P4 does not exhibit obvious toxicities to
      vaginal tissue in vivo even after repeated application. Efficacy studies
      indicated that GC-P4 was capable of preventing the progression of simple
      endometrial hyperplasia (SEH) to complex atypical endometrial hyperplasia (CAEH)
      in vivo. CONCLUSIONS: Results indicates that GC-P4 retains many characteristics
      for an effective vaginal delivery system for P4. Therefore we believe that GC-P4
      formulation is a promising alternative to current vaginal P4 formulation.

PMID- 25609013
TI  - Synthesis and evaluation of mesoporous carbon/lipid bilayer nanocomposites for
      improved oral delivery of the poorly water-soluble drug, nimodipine.
AB  - PURPOSE: A novel mesoporous carbon/lipid bilayer nanocomposite (MCLN) with a core
      shell structure was synthesized and characterized as an oral drug delivery system
      for poorly water-soluble drugs. The objective of this study was to investigate
      the potential of MCLN-based formulation to modulate the in vitro release and in
      vivo absorption of a model drug, nimodipine (NIM). METHODS: NIM-loaded MCLN was
      prepared by a procedure involving a combination of thin-film hydration and
      lyophilization. Scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), specific surface area analysis, differential scanning
      calorimetry (DSC) and X-ray diffraction (XRD) were employed to characterize the
      NIM-loaded MCLN formulation. The effect of MCLN on cell viability was assessed
      using the MTT assay. In addition, the oral bioavailability of NIM-loaded MCLN in
      beagle dogs was compared with that of the immediate-release formulation,
      Nimotop(r). RESULTS: Our results demonstrate that the NIM-loaded MCLN formulation
      exhibited a typical sustained release pattern. The NIM-loaded MCLN formulation
      achieved a greater degree of absorption and longer lasting plasma drug levels
      compared with the commercial formulation. The relative bioavailability of NIM for
      NIM-loaded MCLN was 214%. MCLN exhibited negligible toxicity. CONCLUSION: The
      data reported herein suggest that the MCLN matrix is a promising carrier for
      controlling the drug release rate and improving the oral absorption of poorly
      water-soluble drugs.

PMID- 25609014
TI  - Effective optical identification of type "0-IIb" early gastric cancer with narrow
      band imaging magnification endoscopy, successfully treated by endoscopic
      submucosal dissection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is currently considered the
      minimal invasive endoscopic treatment for early gastric cancer. Most superficial
      gastric neoplastic lesions are depressed type "0-IIc" (70-80%), while totally
      flat, classified as type "0-IIb" early gastric cancer, is rarely reported (0.4%).
      The aim of the present study was to assess the efficacy of narrow band imaging
      (NBI) magnification endoscopy in identifying type "0-IIb" early gastric cancer
      and ESD treatment with curative intention. METHODS: Twelve of 615 (2%) patients
      (10 males, median 72 years), treated by ESD at our center, were diagnosed as type
      "0-IIb" gastric cancer. Ten had exclusively type "0-IIb", while two had combined
      types "0-IIb+IIc" and "0-IIa+IIb" gastric cancer. Initial diagnosis was made
      during screening gastroscopy, while NBI magnification endoscopy combined with
      indigo-carmine chromoendoscopy were also used. RESULTS: White light endoscopy
      showed only superficial redness. One patient with signet-ring carcinoma showed
      whitish appearance. Indigo-carmine chromoendoscopy showed better visualization,
      while NBI magnification endoscopy revealed abnormal mucosal microsurface and
      microvascular findings which enabled border marking. ESD with curative intention
      was completed without complications. Histological examination showed complete
      (R0) resection, in 10 patients (83%). One patient with positive margins received
      additional surgery (8%). Mean procedure time was 149 (range 60-190) min. One to
      six years post-ESD all patients remain alive. CONCLUSIONS: ESD is considered a
      safe and effective curative treatment for type "0-IIb" gastric cancer, resulting
      in long-term disease-free survival. NBI magnification endoscopy is effective for
      accurate optical identification and border marking of type "0-IIb" early gastric
      cancer.

PMID- 25609016
TI  - Metabolomics-derived prostate cancer biomarkers: fact or fiction?
AB  - Despite continuing research for precise probing and grading of prostate cancer
      (PC) biomarkers, the indexes lack sensitivity and specificity. To search for PC
      biomarkers, we used proton nuclear magnetic resonance ((1)H NMR)-derived serum
      metabolomics. The study comprises 102 serum samples obtained from low-grade (LG,
      n = 40) and high-grade (HG, n = 30) PC cases and healthy controls (HC, n = 32).
      (1)H NMR-derived serum data were examined using principal component analysis and
      orthogonal partial least-squares discriminant analysis. The strength of the model
      was verified by internal cross-validation using the same samples divided into 70%
      as training and 30% as test data sets. Receiver operating characteristic (ROC)
      curve examination was also achieved. Serum metabolomics reveals that four
      biomarkers (alanine, pyruvate, glycine, and sarcosine) were able to accurately
      (ROC 0.966) differentiate 90.2% of PC cases with 84.4% sensitivity and 92.9%
      specificity compared with HC. Similarly, three biomarkers, alanine, pyruvate, and
      glycine, were able to precisely (ROC 0.978) discriminate 92.9% of LG from HG PC
      with 92.5% sensitivity and 93.3% specificity. The robustness of these biomarkers
      was confirmed by prediction of the test data set with >99% diagnostic precision
      for PC determination. These findings demonstrate that (1)H NMR-based serum
      metabolomics is a promising approach for probing and grading PC. 

PMID- 25609017
TI  - Structural and magnetic properties of oxyquinolinate clusters of cobalt(II) and
      manganese(II) and serendipitous intake of carbonate during synthesis.
AB  - During transformation of a tetra-nuclear cobalt oxiquinolinate cluster to a deca
      nuclear cobalt oxyquinolinate cluster, serendipitous intake of a carbonate ion
      was observed. By following a similar synthetic path, a deca-nuclear manganese
      oxyquinolinate cluster was prepared. These clusters show anti-ferromagnetic
      behavior. 

PMID- 25609015
TI  - Whole-exome sequencing reveals the mutational spectrum of testicular germ cell
      tumours.
AB  - Testicular germ cell tumours (TGCTs) are the most common cancer in young men.
      Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study
      the cancer's mutational profile. The mutation rate is uniformly low in all of the
      tumours (mean 0.5 mutations per Mb) as compared with common cancers, consistent
      with the embryological origin of TGCT. In addition to expected copy number gain
      of chromosome 12p and mutation of KIT, we identify recurrent mutations in the
      tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring
      amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4 Mb
      region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour
      XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our
      findings provide further insights into genes involved in the development and
      progression of TGCT.

PMID- 25609018
TI  - Desmoplastic small-round-cell rectal tumor.

PMID- 25609019
TI  - Safety and efficacy of alirocumab 150 mg every 2 weeks, a fully human proprotein
      convertase subtilisin/kexin type 9 monoclonal antibody: A Phase II pooled
      analysis.
AB  - BACKGROUND: Alirocumab, a fully human monoclonal antibody to proprotein
      convertase subtilisin/kexin type 9, is in Phase III development for the treatment
      of hypercholesterolemia. In Phase II studies, 150 mg every 2 weeks (Q2W) was the
      highest Q2W dose studied, and it is currently the highest Q2W dose under
      development. To better assess the safety and efficacy of this dose, data across
      three Phase II studies were pooled. METHODS: We analyzed data from three double
      blind, randomized, placebo-controlled Phase II studies of 8 or 12 weeks'
      duration. In the current analysis, 77 patients were randomized to the control
      group and 108 were randomized to alirocumab 150 mg Q2W administered via a single
      1 mL subcutaneous injection. RESULTS: Adverse events (AEs) occurred in 58.3% of
      alirocumab patients compared with 54.5% of placebo-controlled patients. The most
      common AE was mild, transient injection-site reactions. No signal for muscle
      symptoms such as myalgia and no cases of neurocognitive effects were reported or
      observed. One alirocumab patient, also receiving atorvastatin 80 mg/day, had an
      increase in aspartate transaminase 3 to 5 times the upper limit of normal.
      Alirocumab 150 mg Q2W reduced low-density lipoprotein cholesterol (LDL-C) from
      baseline by 68.4% compared with 10.5% for the control group. More than 90% of
      patients achieved an LDL-C target of < 70 mg/dL with alirocumab versus 8% with
      control. Marked reductions in other atherogenic lipids and modest increases in
      high-density lipoprotein cholesterol were also observed. CONCLUSION: At the
      highest Q2W dose under development (150 mg), alirocumab appears well tolerated
      and produces robust LDL-C reductions. These data suggest that alirocumab 150 mg
      Q2W is an appropriate dose for further evaluation in Phase III trials.

PMID- 25609020
TI  - Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio)
      challenged with a high carbohydrate diet: effects of an acute glucose stimulus
      during late embryonic life.
AB  - Knowledge on the role of early nutritional stimuli as triggers of metabolic
      pathways in fish is extremely scarce. The objective of the present study was to
      assess the long-term effects of glucose injection in the yolk (early stimulus) on
      carbohydrate metabolism and gene regulation in zebrafish juveniles challenged
      with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d
      post-fertilisation (dpf) with either glucose (2 M) or saline solutions. Up to 25
      dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was
      followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles
      were not affected by injection or the HC diet. Glucose stimulus induced some long
      term metabolic changes in the juveniles, as shown by the altered expression of
      genes involved in glucose metabolism. On glycolysis, the expression levels of
      hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the
      visceral and muscle tissues, respectively, of juveniles exposed to the glucose
      stimulus, indicating a possible improvement in glucose oxidation. On
      gluconeogenesis, the inhibition of the expression levels of PEPCK in fish
      injected with glucose suggested lower production of hepatic glucose.
      Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK
      expression reduced by glucose stimulus, leaving the possibility of a specific
      regulation of the FBP-6PFK metabolic cycle. Glucose metabolism in juveniles was
      estimated using a [14C]glucose tracer; fish previously exposed to the stimulus
      showed lower retention of [14C]glucose in visceral tissue (but not in muscle
      tissue) and, accordingly, higher glucose catabolism, in comparison with the
      saline group. Globally, our data suggest that glucose stimulus at embryo stage
      has the potential to alter particular steps of glucose metabolism in zebrafish
      juveniles.

PMID- 25609021
TI  - Catalysed ozonation for removal of an endocrine-disrupting compound using the
      O3/Fenton reagents system.
AB  - Aqueous solutions of diethyl phthalate (DEP) were oxidized by using ozone
      combined with Fenton reagents. The effects of operating parameters such as
      initial pH; initial concentration of DEP, H2O2 and Fe2+; [H2O2]0/[Fe2+]0 ratio
      and O3 dosage on the degradation rates of DEP were investigated. The results
      showed that DEP degradation is strongly dependant on the pH; initial
      concentrations of the phthalate, H2O2 and Fe2+; [H2O2]0/[Fe2+]0 ratio and O3
      dosage. The addition of H2O2 and Fe2+ ions was effective to achieve almost 98%
      degradation of 200 mg L(-1) of DEP in about 40 min using a dose of O3=45 g m(-3)
      NTP; [H2O2]0=2.5*10(-2) mol L(-1) and [Fe(II)]0=5*10(-3) mol L(-1), as compared
      to over 60 min by using O3 and Fenton processes applied separately. DEP
      degradation followed apparent pseudo-first-order kinetics under ozonation,
      Fenton's reagents oxidation and the combined ozonation/Fenton reagents oxidation
      process. The overall reaction rates were significantly enhanced in the
      O3/Fe2+/H2O2 oxidation system, and allows achieving 100% degradation of DEP (100
      mg L(-1)) in 30 min of reaction time. The notable decrease in DEP removal rate
      observed in the presence of a radical scavenger indicates that there was an
      obvious synergetic effect in the combined ozonation/Fenton reagent process most
      likely because ozonation could accelerate Fenton reagents to generate hydroxyl
      radical HO*. Thus, the reaction between DEP and HO* proceeds mainly in the bulk
      of the aqueous phase. Under optimal conditions, the O3/Fe2+/H2O2 system oxidation
      was the most effective in DEP removal in water.

PMID- 25609022
TI  - DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer.
AB  - BACKGROUND: Epithelial-to mesenchymal transition (EMT) involves in metastasis,
      causing loss of epithelial polarity. Metastasis is the major cause of carcinoma
      induced death, but mechanisms are poorly understood. Here we identify
      differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a protein
      belongs to the membrane-associated cytoskeleton protein 4.1 family, as an
      efficient suppressor of EMT in lung cancer. METHODS: The relationship between DAL
      1 and EMT markers were analyzed by using immunohistochemistry in the clinical
      lung cancer tissues. Quantitative real-time PCR and western blot were used to
      characterize the expression of the EMT indicator mRNAs and proteins in DAL-1
      overexpressed or knockdown cells. DAL-1 combined proteins were assessed by co
      immunoprecipitation. RESULTS: DAL-1 levels were strongly reduced even lost in
      lymph node metastasis and advanced pathological stage of human lung carcinomas.
      Overexpression of DAL-1 altered the expression of numerous EMT markers, such as E
      cadherin, beta-catenin Vimentin and N-cadherin expression, meanwhile changed the
      morphological shape of lung cancer cells, and whereas silencing DAL-1 had an
      opposite effect. DAL-1 directly combined with E-cadherin promoter and regulated
      its expression that could be the reason for impairing EMT and decreasing cell
      migration and invasion. Strikingly, HSPA5 was found as DAL-1 direct binding
      protein. CONCLUSIONS: These results suggest that tumor suppressor DAL-1 could
      also attenuate EMT and be important for tumor metastasis in the early
      transformation process in lung cancer.

PMID- 25609023
TI  - Quantitative assessment of patellar vascularity following bone-patellar tendon
      bone autograft harvest for ACL reconstruction.
AB  - PURPOSE: Recent anatomic studies have suggested that the dominant arterial supply
      of the patella enters through the inferior pole. Based upon these findings, we
      hypothesized that bone-patellar tendon-bone graft harvest can significantly
      diminish patellar vascularity. METHODS: Nine matched pair cadaveric knee
      specimens (mean age 47.4 years) were dissected and cannulated. A single knee was
      selected to undergo routine graft harvest, and the contralateral knee was left
      intact to serve as a control. Gadolinium was injected, and magnetic resonance
      imaging (MRI) signal enhancement was quantified to determine differences in
      uptake. Each matched pair was subsequently injected with a urethane polymer
      compound and dissected to correlate vessel disruption with MRI findings. RESULTS:
      We identified two predominating patterns of vessel entry. In one pattern, the
      vessel entered the inferomedial aspect (five o'clock/right, seven o'clock/left)
      of the patella and was disrupted by graft harvest in 2/9 (22.2 %) pairs. In the
      second pattern, the vessel entered further medial (four o'clock/right, eight
      o'clock/left) and was not disrupted (7/9, 78.8 %). The mean decrease in
      gadolinium uptake following disruption of the predominant vessel measured 56.2 %
      (range 42.6-69.5 %) compared to an average decrease of 18.3 % (range 7.1-29.1 %)
      when the dominant arterial supply to the inferior pole remained intact (p <
      0.04). CONCLUSION: Medial entry of the predominant vessel precluded vessel
      disruption. Disruption of the dominant arterial supply can result in a
      significant decrease in patellar vascularity. Modification of graft harvest
      techniques and areas of surgical dissection should be explored to minimize
      vascular insult. Further correlation with clinical studies/outcomes is necessary
      to determine a potential association between vascular insult and anterior knee
      pain.

PMID- 25609026
TI  - Ultrasensitive and highly selective detection of bioaccumulation of methyl
      mercury in fish samples via Ag0/Hg0 amalgamation.
AB  - Methylmercury (CH3Hg(+)), the common organic source of mercury, is well-known as
      one of the most toxic compounds that is more toxic than inorganic or elemental
      mercury. In seabeds, the deposited Hg(2+) ions are converted into CH3Hg(+) by
      bacteria, where they are subsequently consumed and bioaccumulated in the tissue
      of fish, and finally, to enter the human diet, causing severe health problems.
      Therefore, sensitive and selective detection of bioaccumulation of CH3Hg(+) in
      fish samples is desirable. However, selective assay of CH3Hg(+) in the mercury
      containing samples has been seriously hampered by the difficulty to distinguish
      CH3Hg(+) from ionic mercury. We report here that metal amalgamation, a natural
      phenomenon occurring between mercury atoms and certain metal atoms, combining
      with DNA-protected silver nanoparticles, can be used to detect CH3Hg(+) with high
      sensitivity and superior selectivity over Hg(2+) and other heavy metals. In our
      proposed approach, discrimination between CH3Hg(+) and Hg(2+) ions was realized
      by forming Ag/Hg amalgam with a CH3Hg(+)-specific scaffold. We have found that
      Ag/Hg amalgam can be formed on a CH3Hg(+)-specific DNA template between silver
      atoms and mercury atoms but cannot between silver atoms and CH3Hg(+). With a dye
      labeled DNA strand, the sensor can detect CH3Hg(+) down to the picomolar level,
      which is >125-fold sensitive over Hg(2+). Moreover, the presence of 50-fold
      Hg(2+) and 10(6)-fold other metal ions do not interfere with the CH3Hg(+)
      detection. The results shown herein have important implications for the fast,
      easy, and selective detection and monitoring of CH3Hg(+) in environmental and
      biological samples. 

PMID- 25609027
TI  - The effect of polysaccharide types on adsorption properties of LbL assembled
      multilayer films.
AB  - Three types of biocompatible films were fabricated via electrostatic layer-by
      layer (LbL) adsorption of oppositely charged cationic polyurethane and anionic
      polysaccharides with different primary structures, including sodium hyaluronate,
      sodium carboxymethyl cellulose and sodium alginate. The adsorption behaviors of
      films were investigated by using the cationic dye methylene blue (MB) as a model
      drug at various pH values and salt concentrations. The relationship between the
      type of polysaccharide and the adsorption behavior of LbL films was comparatively
      studied. It was found that the adsorption capacity increased with an increase of
      the initial concentration of MB in the concentration range of the experiment to
      all of the films, and the pH of environment ranged from 3.0 to 9.0. The Langmuir
      equation fit perfectly to the experiment data. In addition, a pseudo second-order
      adsorption model can well describe the adsorption behaviors of MB for three
      films. The results showed that the type of side chains and the charge density of
      the polysaccharides played key roles in the adsorption properties of the
      PU/polysaccharide multilayer films. 

PMID- 25609025
TI  - Placebo effects on itch: a meta-analysis of clinical trials of patients with
      dermatological conditions.
AB  - Although placebo contributes to the effects of treatment for various symptoms and
      conditions, its effect on itch has rarely been investigated. In this meta
      analysis, the magnitude of the placebo effect on itch was systematically
      investigated in clinical trials including patients with chronic itch due to
      atopic dermatitis, psoriasis, or chronic idiopathic urticaria. From searches in
      four databases, 34 articles were included in the quantitative analyses. Placebo
      treatment significantly decreased itch (1.3 out of 10, 95% confidence interval
      1.02-1.61) compared with baseline itch (effect size 0.55), indicating that
      placebo effects have a considerable role in these patients' treatment. 

PMID- 25609028
TI  - A robust asymmetry in loudness between rising- and falling-intensity tones.
AB  - Tones rising in intensity over a few seconds are perceived as louder than
      symmetrical tones falling in intensity. However, the causes for such perceptual
      asymmetry, as well as its magnitude and dependency on contextual and
      methodological factors remain unclear. In this paper, two psychophysical
      experiments were conducted to measure the magnitude of this asymmetry for 2-s, 15
      dB intensity-varying tones in different conditions. In the first experiment,
      participants assessed the global loudness of rising- and falling-intensity sounds
      with an absolute magnitude estimation procedure (AME); in the second experiment,
      they compared sounds relatively in an adaptive, two-interval, two-alternative
      forced-choice task (2I-2AFC). In both experiments, the region of intensity
      change, the design of experimental blocks, and the type of comparison stimulus
      were systematically manipulated to test for contextual and methodological
      factors. Remarkably, the asymmetry was virtually unaffected by the different
      contexts of presentation and similar results with 2I-2AFC and AME measurements
      were obtained. In addition, the size of the effect was comparable over all but
      the highest intensity regions (80-90 dB SPL), at which it was significantly
      smaller. All together, these results indicate that the loudness asymmetry is
      preserved under different measurement methods and contexts, and suggest that the
      underlying mechanism is strong and robust. In short, falling tones have to be
      about 4 dB higher in level than symmetrically rising tones in order to be
      perceived with the same global loudness, a finding that is still not predicted by
      current loudness models.

PMID- 25609029
TI  - Modifiable risk factors associated with prediabetes in men and women: a cross
      sectional analysis of the cohort study in primary health care on the evolution of
      patients with prediabetes (PREDAPS-Study).
AB  - BACKGROUND: Prediabetes is a high-risk state for diabetes development, but little
      is known about the factors associated with this state. The aim of the study was
      to identify modifiable risk factors associated with the presence of prediabetes
      in men and women. METHODS: Cohort Study in Primary Health Care on the Evolution
      of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort
      of 1184 subjects with prediabetes and another cohort of 838 subjects without
      glucose metabolism disorders. It is being conducted by 125 general practitioners
      in Spain. Data for this analysis were collected during the baseline stage in
      2012. The modifiable risk factors included were: smoking habit, alcohol
      consumption, low physical activity, inadequate diet, hypertension, dyslipidemia,
      and obesity. To assess independent association between each factor and
      prediabetes, odds ratios (ORs) were estimated using logistic regression models.
      RESULTS: Abdominal obesity, low plasma levels of high-density lipoprotein
      cholesterol (HDL-cholesterol), and hypertension were independently associated
      with the presence of prediabetes in both men and women. After adjusting for all
      factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79),
      1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12
      2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in
      both sexes but did not reach statistical significance among men, after adjusting
      for all factors. Risky alcohol consumption was a risk factor for prediabetes in
      men, OR 1.49 (1.00-2.24). CONCLUSIONS: Obesity, low HDL-cholesterol levels, and
      hypertension were modifiable risk factors independently related to the presence
      of prediabetes in both sexes. The magnitudes of the associations were stronger
      for men than women. Abdominal obesity in both men and women displayed the
      strongest association with prediabetes. The findings suggest that there are some
      differences between men and women, which should be taken into account when
      implementing specific recommendations to prevent or delay the onset of diabetes
      in adult population.

PMID- 25609030
TI  - Total hospital stay for hip fracture: measuring the variations due to pre
      fracture residence, rehabilitation, complications and comorbidities.
AB  - BACKGROUND: Hospital treatment for hip fracture is complex, often involving
      sequential episodes for acute orthopaedics, rehabilitation and care of contingent
      conditions. Most reports of hospital length of stay (LOS) address only the acute
      phase of care. This study identifies the frequency and mean duration of the
      component episodes within total hospital stay, and measures the impacts of
      patient-level and clinical service variables upon both acute phase and total LOS.
      METHODS: Administrative datasets for 2552 subjects hospitalised between 1 July
      2008 and 30 June 2009 were linked. Associations between LOS, pre-fracture
      accommodation status, age, sex, fracture type, hospital separation codes,
      selected comorbidities and complications were examined in regression models for
      acute phase and total LOS for patients from residential aged care (RAC) and from
      the community. RESULTS: Mean total LOS was 30.8 days, with 43 per cent
      attributable to acute fracture management, 37 per cent to rehabilitation and 20
      per cent to management of contingent conditions. Community patients had
      unadjusted total LOS of 35.4 days compared with 18.8 days for RAC patients (p
      <0.001). The proportion of transfers into rehabilitation (57 per cent vs 17 per
      cent, p <0.001) was the major determinant for this difference. In multivariate
      analyses, new RAC placement, discharge to other facilities, and complications of
      pressure ulcer, urinary or surgical site infections increased LOS by at least
      four days in one or more phases of hospital stay. CONCLUSION: Pre-fracture
      residence, selection for rehabilitation, discharge destination and specific
      complications are key determinants for acute phase and total LOS. Calculating the
      dimensions of specific determinants for LOS may identify potential efficiencies
      from targeted interventions such as orthogeriatric care models.

PMID- 25609031
TI  - Breaking the co-operation between bystander T-cells and natural killer cells
      prevents the development of immunosuppression after traumatic skeletal muscle
      injury in mice.
AB  - Nosocomial infections represent serious complications after traumatic or surgical
      injuries in intensive care units. The pathogenesis of the underlying
      immunosuppression is only incompletely understood. In the present study, we
      investigated whether injury interferes with the function of the adaptive immune
      system in particular with the differentiation of antigen-specific T helper (Th)
      cell responses in vivo. We used a mouse model for traumatic gastrocnemius muscle
      injury. Ovalbumin (OVA), which served as a foreign model antigen, was injected
      into the hind footpads for determination of the differentiation of OVA-specific
      Th-cells in the draining popliteal lymph node (pLN). The release of interferon
      (IFN)-gamma from OVA-specific Th-cells was impaired within 24 h after injury and
      this impairment persisted for at least 7 days. In contrast, the proliferation of
      OVA-specific Th-cells remained unaffected. Injury did not modulate the function
      of antigen-presenting cells (APCs) in the pLN. Adoptive transfer of total T-cells
      from pLNs of injured mice inhibited IFN-gamma production by OVA-specific Th-cells
      in naive mice. Suppressed Th1 priming did not occur in lymphocyte-deficient mice
      after injury but was restored by administration of T-cells before injury.
      Moreover, the suppression of Th1 differentiation required the presence of natural
      killer (NK) cells that were recruited to the pLN after injury; this recruitment
      was dependent on lymphocytes, toll-like receptor 4 (TLR4) and myeloid
      differentiation factor 88 (MyD88). In summary, upon traumatic skeletal muscle
      injury T-cells and NK cells together prevent the development of protective Th1
      immunity. Breaking this co-operation might be a novel approach to reduce the risk
      of infectious complications after injury. 

PMID- 25609032
TI  - Clinical evaluation of the efficacy of one self-adhesive composite in dental
      hypersensitivity.
AB  - OBJECTIVES: The aim of the present study was to investigate the clinical
      effectiveness over 12 weeks of Vertise Flow(TM), a self-adhering composite, in
      dental hypersensitivity (DH). MATERIAL AND METHODS: The study was conducted as a
      split-mouth randomized clinical trial. Vertise FlowTM was compared to the
      following: (1) Universal Dentine Sealant, (2) Clearfil Protect Bond, and (3) Flor
      Opal(r) Varnish. A total of 46 patients with 116 hypersensitive teeth were
      studied. Pain experience was generated by a cold stimulus and assessed using the
      visual analog scale (VAS) of pain. The response was recorded before the
      application of the materials (pre-1), immediately after (post-1), at 1- (post-2),
      2- (post-3), and 12-week controls (post-4). Statistical differences in VAS were
      performed using the Kruskal-Wallis analysis at the different time-points (P <
      0.05), adjusting statistical significances for multiple comparisons (Bonferroni
      correction). RESULTS: All the materials showed any statistically significant
      differences at the baseline. After the application of each material, a VAS
      decrease was demonstrated at every post-control. VF showed significant
      hypersensitivity reduction in post-1. Statistically significant relief was also
      observed in post-2 while no significant differences were detected in post-3 and
      post-4. CONCLUSIONS: After 12-week controls, there was no statistically
      significant hypersensitivity reduction using VF in respect to the other
      materials. On the other hand, any significant differences were detected in the
      decrease of the VAS irrespective of the desensitizing agent employed at the 12
      week controls. CLINICAL RELEVANCE: The significant increase in VAS scores within
      the 12-weeks of environment suggested there is instability of VF when used as
      desensitizing agent.

PMID- 25609033
TI  - Two-year clinical performance of a two-step etch-and-rinse adhesive in non
      carious cervical lesions: Influence of subject's age and dentin etching time.
AB  - AIM: The aim of this study was to evaluate the influence of the subject's age and
      dentin etching time on the clinical performance of a two-step etch-and-rinse
      adhesive in class V non-carious cervical lesions (NCCLs). MATERIALS AND METHODS:
      Forty patients with NCCLs (classified as degrees 2 and 3 of dentin sclerosis)
      were enrolled in this study. The lesions were selected and assigned into two
      groups (n = 70/group) according to the subject's age: (G1) between 21-35 years
      old and (G2) between 40-54 years old. Each group was randomly divided into two
      subgroups (n = 35/group) according to dentin etching time using recommended
      application time (15 s) and an extended application time (30 s). A total of 140
      restorations with XP Bond (Dentsply DeTrey, Germany) were placed. The composite
      resin Esthet X (Dentsply) was placed incrementally. All restorations were
      evaluated using the modified USPHS criteria. Data was analyzed by the McNemar and
      chi-square tests (p < 0.05). RESULTS: At the end of 2 years, 132 restorations
      (94.2% recall rate) were evaluated. The 24-month retention rates (%) were 93.5
      for G1(15), 97.1 for G1(30), 93.9 for G2(15), and 97.0 for G2(30). There were no
      statistical differences in the retention rates in each recall period among
      groups. CONCLUSION: For the selected age groups, neither the subject's age nor
      the etching time had any influence on the clinical performance of XP Bond
      adhesive in NCCLs over a 24-month period. CLINICAL RELEVANCE: The clinical
      effectiveness of the XP Bond was excellent after 2 years of clinical service.
      Long-term clinical evaluations are necessary to confirm this finding.

PMID- 25609034
TI  - In vitro enamel remineralization capacity of composite resins containing sodium
      trimetaphosphate and fluoride.
AB  - OBJECTIVES: This study evaluated the in vitro enamel remineralization capacity of
      experimental composite resins containing sodium trimetaphosphate (TMP) combined
      or not with fluoride (F). MATERIALS AND METHODS: Bovine enamel slabs were
      selected upon analysis of initial surface hardness (SH1) and after induction of
      artificial carious lesions (SH2). Experimental resins were as follows: resin C
      (control-no sodium fluoride (NaF) or TMP), resin F (with 1.6% NaF), resin TMP
      (with 14.1% TMP), and resin TMP/F (with NaF and TMP). Resin samples were made and
      attached to enamel slabs (n = 12 slabs per material). Those specimens
      (resin/enamel slab) were subjected to pH cycling to promote remineralization, and
      then final surface hardness (SH3) was measured to calculate the percentage of
      surface hardness recovery (%SH). The integrated recovery of subsurface hardness
      (DeltaKHN) and F concentration in enamel were also determined. Data was analyzed
      by ANOVA and Student-Newman-Keuls test (p < 0.05). RESULTS: Resins F and TMP/F
      showed similar SH3 values (p = 0.478) and %SH (p = 0.336) and differed
      significantly from the other resins (p < 0.001). Considering DeltaKHN values,
      resin TMP/F presented the lowest area of lesion (p < 0.001). The presence of F on
      enamel was different among the fluoridated resins (p = 0.042), but higher than in
      the other resins (p < 0.001). CONCLUSIONS: The addition of TMP to a fluoridated
      composite resin enhanced its capacity for remineralization of enamel in vitro.
      CLINICAL RELEVANCE: The combination of two agents with action on enamel favored
      remineralization, suggesting that composite resins containing sodium
      trimetaphosphate and fluoride could be indicated for clinical procedures in
      situations with higher cariogenic challenges.

PMID- 25609035
TI  - Te/C nanocomposites for Li-Te Secondary Batteries.
AB  - New battery systems having high energy density are actively being researched in
      order to satisfy the rapidly developing market for longer-lasting mobile
      electronics and hybrid electric vehicles. Here, we report a new Li-Te secondary
      battery system with a redox potential of ~1.7 V (vs. Li(+)/Li) adapted on a Li
      metal anode and an advanced Te/C nanocomposite cathode. Using a simple concept of
      transforming TeO2 into nanocrystalline Te by mechanical reduction, we designed an
      advanced, mechanically reduced Te/C nanocomposite electrode material with high
      energy density (initial discharge/charge: 1088/740 mA h cm(-3)), excellent
      cyclability (ca. 705 mA h cm(-3) over 100 cycles), and fast rate capability (ca.
      550 mA h cm(-3) at 5C rate). The mechanically reduced Te/C nanocomposite
      electrodes were found to be suitable for use as either the cathode in Li-Te
      secondary batteries or a high-potential anode in rechargeable Li-ion batteries.
      We firmly believe that the mechanically reduced Te/C nanocomposite constitutes a
      breakthrough for the realization and mass production of excellent energy storage
      systems.

PMID- 25609036
TI  - Psychosocial determinants of physicians' intention to practice euthanasia in
      palliative care.
AB  - BACKGROUND: Euthanasia remains controversial in Canada and an issue of debate
      among physicians. Most studies have explored the opinion of health professionals
      regarding its legalization, but have not investigated their intentions when faced
      with performing euthanasia. These studies are also considered atheoretical. The
      purposes of the present study were to fill this gap in the literature by
      identifying the psychosocial determinants of physicians' intention to practice
      euthanasia in palliative care and verifying whether respecting the patient's
      autonomy is important for physicians. METHODS: A validated anonymous
      questionnaire based on an extended version of the Theory of Planned Behavior was
      mailed to a random sample of 445 physicians from the province of Quebec, Canada.
      RESULTS: The response rate was 38.3% and the mean score for intention was 3.94 +/
      2.17 (range: 1 to 7). The determinants of intention among physicians were:
      knowing patients' wishes (OR = 10.77; 95%CI: 1.33-86.88), perceived behavioral
      control-physicians' evaluation of their ability to adopt a given behavior-(OR =
      4.35; 95%CI: 1.44-13.15), moral norm-the appropriateness of adopting a given
      behavior according to one's personal and moral values-(OR = 3.22; 95%CI: 1.29
      8.00) and cognitive attitude-factual consequences of the adoption of a given
      behavior-(OR = 3.16; 95%CI: 1.20-8.35). This model correctly classified 98.8% of
      physicians. Specific beliefs that might discriminate physicians according to
      their level of intention were also identified. For instance, physicians' moral
      norm was related to the ethical principle of beneficence. CONCLUSIONS: Overall,
      physicians have weak intentions to practice euthanasia in palliative care.
      Nevertheless, respecting patients' final wishes concerning euthanasia seems to be
      of particular importance to them and greatly affects their motivation to perform
      euthanasia.

PMID- 25609037
TI  - An in vitro model of tissue boundary formation for dissecting the contribution of
      different boundary forming mechanisms.
AB  - During development and in adult tissues separation of phenotypically distinct
      cell populations is necessary to ensure proper organization and function of
      tissues and organs. Various phenomena, such as differential adhesion,
      differential mechanical tension and cell-cell repulsion, are proposed to cause
      boundary formation. Moreover, emerging evidence suggests that interplay between
      multiple such phenomena can underlie boundary formation. Boundary-forming
      mechanisms are commonly studied in vivo in complex embryo models or in vitro
      using simple model systems not reflective of in vivo boundary complexity. To
      better elucidate the interplay between multiple boundary formation mechanism,
      there is therefore a need for more relevant in vitro model systems that allow
      quantitative and concomitant studies of the multiple changes in cell/tissue
      behaviour that lead to boundary establishment. Here, we develop such a model
      using patterned co-cultures of two cell populations. Using a set of quantitative
      tools, we demonstrate that our approach allows us to study the mechanisms
      underlying boundary formation. We demonstrate that in our specific system
      differential mechanical tension and modulation of migratory behavior of cells
      accompany boundary formation. The design of our in vitro model system will allow
      researchers to obtain quantitative, integrative mechanistic data facilitating a
      faster and more thorough understanding of the fundamental principles underlying
      boundary formation. 

PMID- 25609038
TI  - A steady-state Kalman predictor-based filtering strategy for non-overlapping sub
      band spectral estimation.
AB  - This paper focuses on suppressing spectral overlap for sub-band spectral
      estimation, with which we can greatly decrease the computational complexity of
      existing spectral estimation algorithms, such as nonlinear least squares spectral
      analysis and non-quadratic regularized sparse representation. Firstly, our study
      shows that the nominal ability of the high-order analysis filter to suppress
      spectral overlap is greatly weakened when filtering a finite-length sequence,
      because many meaningless zeros are used as samples in convolution operations.
      Next, an extrapolation-based filtering strategy is proposed to produce a series
      of estimates as the substitutions of the zeros and to recover the suppression
      ability. Meanwhile, a steady-state Kalman predictor is applied to perform a
      linearly-optimal extrapolation. Finally, several typical methods for spectral
      analysis are applied to demonstrate the effectiveness of the proposed strategy. 

PMID- 25609039
TI  - Sign language recognition with the Kinect sensor based on conditional random
      fields.
AB  - Sign language is a visual language used by deaf people. One difficulty of sign
      language recognition is that sign instances of vary in both motion and shape in
      three-dimensional (3D) space. In this research, we use 3D depth information from
      hand motions, generated from Microsoft's Kinect sensor and apply a hierarchical
      conditional random field (CRF) that recognizes hand signs from the hand motions.
      The proposed method uses a hierarchical CRF to detect candidate segments of signs
      using hand motions, and then a BoostMap embedding method to verify the hand
      shapes of the segmented signs. Experiments demonstrated that the proposed method
      could recognize signs from signed sentence data at a rate of 90.4%. 

PMID- 25609041
TI  - Stand-alone and hybrid positioning using asynchronous pseudolites.
AB  - global navigation satellite system (GNSS) receivers are usually unable to achieve
      satisfactory performance in difficult environments, such as open-pit mines, urban
      canyons and indoors. Pseudolites have the potential to extend GNSS usage and
      significantly improve receiver performance in such environments by providing
      additional navigation signals. This also applies to asynchronous pseudolite
      systems, where different pseudolites operate in an independent way. Asynchronous
      pseudolite systems require, however, dedicated strategies in order to properly
      integrate GNSS and pseudolite measurements. In this paper, several asynchronous
      pseudolite/GNSS integration strategies are considered: loosely- and tightly
      coupled approaches are developed and combined with pseudolite proximity and
      receiver signal strength (RSS)-based positioning. The performance of the
      approaches proposed has been tested in different scenarios, including static and
      kinematic conditions. The tests performed demonstrate that the methods developed
      are effective techniques for integrating heterogeneous measurements from
      different sources, such as asynchronous pseudolites and GNSS. 

PMID- 25609040
TI  - A novel ultrasound technique for detection of osteochondral defects in the ankle
      joint: a parametric and feasibility study.
AB  - (Osteo)chondral defects (OCDs) in the ankle are currently diagnosed with
      modalities that are not convenient to use in long-term follow-ups. Ultrasound
      (US) imaging, which is a cost-effective and non-invasive alternative, has limited
      ability to discriminate OCDs. We aim to develop a new diagnostic technique based
      on US wave propagation through the ankle joint. The presence of OCDs is
      identified when a US signal deviates from a reference signal associated with the
      healthy joint. The feasibility of the proposed technique is studied using
      experimentally-validated 2D finite-difference time-domain models of the ankle
      joint. The normalized maximum cross correlation of experiments and simulation was
      0.97. Effects of variables relevant to the ankle joint, US transducers and OCDs
      were evaluated. Variations in joint space width and transducer orientation made
      noticeable alterations to the reference signal: normalized root mean square error
      ranged from 6.29% to 65.25% and from 19.59% to 8064.2%, respectively. The results
      suggest that the new technique could be used for detection of OCDs, if the
      effects of other parameters (i.e., parameters related to the ankle joint and US
      transducers) can be reduced. 

PMID- 25609042
TI  - Combined use of terrestrial laser scanning and IR thermography applied to a
      historical building.
AB  - The conservation of architectural heritage usually requires a multidisciplinary
      approach involving a variety of specialist expertise and techniques.
      Nevertheless, destructive techniques should be avoided, wherever possible, in
      order to preserve the integrity of the historical buildings, therefore the
      development of non-destructive and non-contact techniques is extremely important.
      In this framework, a methodology for combining the terrestrial laser scanning and
      the infrared thermal images is proposed, in order to obtain a reconnaissance of
      the conservation state of a historical building. The proposed case study is
      represented by St. Augustine Monumental Compound, located in the historical
      centre of the town of Cosenza (Calabria, South Italy). Adopting the proposed
      methodology, the paper illustrates the main results obtained for the building
      test overlaying and comparing the collected data with both techniques, in order
      to outline the capabilities both to detect the anomalies and to improve the
      knowledge on health state of the masonry building. The 3D model, also, allows to
      provide a reference model, laying the groundwork for implementation of a
      monitoring multisensor system based on the use of non-destructive techniques. 

PMID- 25609043
TI  - Evaluation of the leap motion controller as a new contact-free pointing device.
AB  - This paper presents a Fitts' law-based analysis of the user's performance in
      selection tasks with the Leap Motion Controller compared with a standard mouse
      device. The Leap Motion Controller (LMC) is a new contact-free input system for
      gesture-based human-computer interaction with declared sub-millimeter accuracy.
      Up to this point, there has hardly been any systematic evaluation of this new
      system available. With an error rate of 7.8% for the LMC and 2.8% for the mouse
      device, movement times twice as large as for a mouse device and high overall
      effort ratings, the Leap Motion Controller's performance as an input device for
      everyday generic computer pointing tasks is rather limited, at least with regard
      to the selection recognition provided by the LMC. 

PMID- 25609044
TI  - Modified OMP algorithm for exponentially decaying signals.
AB  - A group of signal reconstruction methods, referred to as compressed sensing (CS),
      has recently found a variety of applications in numerous branches of science and
      technology. However, the condition of the applicability of standard CS algorithms
      (e.g., orthogonal matching pursuit, OMP), i.e., the existence of the strictly
      sparse representation of a signal, is rarely met. Thus, dedicated algorithms for
      solving particular problems have to be developed. In this paper, we introduce a
      modification of OMP motivated by nuclear magnetic resonance (NMR) application of
      CS. The algorithm is based on the fact that the NMR spectrum consists of
      Lorentzian peaks and matches a single Lorentzian peak in each of its iterations.
      Thus, we propose the name Lorentzian peak matching pursuit (LPMP). We also
      consider certain modification of the algorithm by introducing the allowed
      positions of the Lorentzian peaks' centers. Our results show that the LPMP
      algorithm outperforms other CS algorithms when applied to exponentially decaying
      signals. 

PMID- 25609045
TI  - A structure fidelity approach for big data collection in wireless sensor
      networks.
AB  - One of the most widespread and important applications in wireless sensor networks
      (WSNs) is the continuous data collection, such as monitoring the variety of
      ambient temperature and humidity. Due to the sensor nodes with a limited energy
      supply, the reduction of energy consumed in the continuous observation of
      physical phenomenon plays a significant role in extending the lifetime of WSNs.
      However, the high redundancy of sensing data leads to great waste of energy as a
      result of over-deployed sensor nodes. In this paper, we develop a structure
      fidelity data collection (SFDC) framework leveraging the spatial correlations
      between nodes to reduce the number of the active sensor nodes while maintaining
      the low structural distortion of the collected data. A structural distortion
      based on the image quality assessment approach is used to perform the nodes
      work/sleep scheduling, such that the number of the working nodes is reduced while
      the remainder of nodes can be put into the low-power sleep mode during the
      sampling period. The main contribution of SFDC is to provide a unique perspective
      on how to maintain the data fidelity in term of structural similarity in the
      continuous sensing applications for WSNs. The simulation results based on
      synthetic and real world datasets verify the effectiveness of SFDC framework both
      on energy saving and data fidelity. 

PMID- 25609046
TI  - New research on MEMS acoustic vector sensors used in pipeline ground markers.
AB  - According to the demands of current pipeline detection systems, the above-ground
      marker (AGM) system based on sound detection principle has been a major
      development trend in pipeline technology. A novel MEMS acoustic vector sensor for
      AGM systems which has advantages of high sensitivity, high signal-to-noise ratio
      (SNR), and good low frequency performance has been put forward. Firstly, it is
      presented that the frequency of the detected sound signal is concentrated in a
      lower frequency range, and the sound attenuation is relatively low in soil.
      Secondly, the MEMS acoustic vector sensor structure and basic principles are
      introduced. Finally, experimental tests are conducted and the results show that
      in the range of 0 degrees ~90 degrees , when r = 5 m, the proposed MEMS acoustic
      vector sensor can effectively detect sound signals in soil. The measurement
      errors of all angles are less than 5 degrees . 

PMID- 25609047
TI  - CCS-DTN: clustering and network coding-based efficient routing in social DTNs.
AB  - With the development of mobile Internet, wireless communication via mobile
      devices has become a hot research topic, which is typically in the form of Delay
      Tolerant Networks (DTNs). One critical issue in the development of DTNs is
      routing. Although there is a lot research work addressing routing issues in DTNs,
      they cannot produce an advanced solution to the comprehensive challenges since
      only one or two aspects (nodes' movements, clustering, centricity and so on) are
      considered when the routing problem is handled. In view of these defects in the
      existing works, we propose a novel solution to address the routing issue in
      social DTNs. By this solution, mobile nodes are divided into different clusters.
      The scheme, Spray and Wait, is used for the intra-cluster communication while a
      new forwarding mechanism is designed for the inter-cluster version. In our
      solution, the characteristics of nodes and the relation between nodes are fully
      considered. The simulation results show that our proposed scheme can
      significantly improve the performance of the routing scheme in social DTNs. 

PMID- 25609048
TI  - An efficient approach for pixel decomposition to increase the spatial resolution
      of land surface temperature images from MODIS thermal infrared band data.
AB  - Land surface temperature (LST) images retrieved from the thermal infrared (TIR)
      band data of Moderate Resolution Imaging Spectroradiometer (MODIS) have much
      lower spatial resolution than the MODIS visible and near-infrared (VNIR) band
      data. The coarse pixel scale of MODIS LST images (1000 m under nadir) have
      limited their capability in applying to many studies required high spatial
      resolution in comparison of the MODIS VNIR band data with pixel scale of 250-500
      m. In this paper we intend to develop an efficient approach for pixel
      decomposition to increase the spatial resolution of MODIS LST image using the
      VNIR band data as assistance. The unique feature of this approach is to maintain
      the thermal radiance of parent pixels in the MODIS LST image unchanged after they
      are decomposed into the sub-pixels in the resulted image. There are two important
      steps in the decomposition: initial temperature estimation and final temperature
      determination. Therefore the approach can be termed double-step pixel
      decomposition (DSPD). Both steps involve a series of procedures to achieve the
      final result of decomposed LST image, including classification of the surface
      patterns, establishment of LST change with normalized difference of vegetation
      index (NDVI) and building index (NDBI), reversion of LST into thermal radiance
      through Planck equation, and computation of weights for the sub-pixels of the
      resulted image. Since the Advanced Spaceborne Thermal Emission and Reflection
      Radiometer (ASTER) with much higher spatial resolution than MODIS data was on
      board the same platform (Terra) as MODIS for Earth observation, an experiment had
      been done in the study to validate the accuracy and efficiency of our approach
      for pixel decomposition. The ASTER LST image was used as the reference to compare
      with the decomposed LST image. The result showed that the spatial distribution of
      the decomposed LST image was very similar to that of the ASTER LST image with a
      root mean square error (RMSE) of 2.7 K for entire image. Comparison with the
      evaluation DisTrad (E-DisTrad) and re-sampling methods for pixel decomposition
      also indicate that our DSPD has the lowest RMSE in all cases, including urban
      region, water bodies, and natural terrain. The obvious increase in spatial
      resolution remarkably uplifts the capability of the coarse MODIS LST images in
      highlighting the details of LST variation. Therefore it can be concluded that, in
      spite of complicated procedures, the proposed DSPD approach provides an
      alternative to improve the spatial resolution of MODIS LST image hence expand its
      applicability to the real world. 

PMID- 25609049
TI  - Surface plasmon resonator using high sensitive resonance telecommunication
      wavelengths for DNA sensors of Mycobacterium tuberculosis with thiol-modified
      probes.
AB  - Various analytes can be verified by surface plasmon resonance, thus continuous
      improvement of this sensing technology is crucial for better sensing selection
      and higher sensitivity. The SPR sensitivity on the wavelength modulation is
      enhanced with increasing wavelengths. The telecommunication wavelength range was
      then utilized to detect Mycobacterium tuberculosis (MTB) deoxyribonucleic acid
      (DNA) under two situations, without immobilization and with 5'-thiol end labeled
      IS6100 DNA probes, for SPR sensitivity comparison. The experimental data
      demonstrated that the SPR sensitivity increased more than 13 times with the
      wavelength modulation after immobilization. Since the operating wavelength
      accuracy of a tunable laser source can be controlled within 0.001 nm, the
      sensitivity and resolution on immobilized MTB DNA were determined as 1.04
      nm/(MUg/mL) and 0.9 ng/mL, respectively. 

PMID- 25609050
TI  - PET and PVC separation with hyperspectral imagery.
AB  - Traditional plants for plastic separation in homogeneous products employ material
      physical properties (for instance density). Due to the small intervals of
      variability of different polymer properties, the output quality may not be
      adequate. Sensing technologies based on hyperspectral imaging have been
      introduced in order to classify materials and to increase the quality of recycled
      products, which have to comply with specific standards determined by industrial
      applications. This paper presents the results of the characterization of two
      different plastic polymers--polyethylene terephthalate (PET) and polyvinyl
      chloride (PVC)--in different phases of their life cycle (primary raw materials,
      urban and urban-assimilated waste and secondary raw materials) to show the
      contribution of hyperspectral sensors in the field of material recycling. This is
      accomplished via near-infrared (900-1700 nm) reflectance spectra extracted from
      hyperspectral images acquired with a two-linear-spectrometer apparatus. Results
      have shown that a rapid and reliable identification of PET and PVC can be
      achieved by using a simple two near-infrared wavelength operator coupled to an
      analysis of reflectance spectra. This resulted in 100% classification accuracy. A
      sensor based on this identification method appears suitable and inexpensive to
      build and provides the necessary speed and performance required by the recycling
      industry.

PMID- 25609051
TI  - Imaging acute complications in cancer patients: what should be evaluated in the
      emergency setting?
AB  - Increased incidence world-wide of cancer and increased survival has also resulted
      in physicians seeing more complications in patients with cancer. In many cases,
      complications are the first manifestations of the disease. They may be insidious
      and develop over a period of months, or acute and manifest within minutes to
      days. Imaging examinations play an essential role in evaluating cancer and its
      complications. Plain radiography and ultrasonography (US) are generally performed
      initially in an urgent situation due to their wide availability, low cost, and
      minimal or no radiation exposure. However, depending on a patient's symptoms,
      evaluation with cross-sectional imaging methods such as computed tomography (CT)
      and magnetic resonance imaging (MRI) is often necessary. In this review article,
      we discuss some of the most important acute noninfectious oncological
      complications for which imaging methods play an essential role in diagnosis. 

PMID- 25609053
TI  - Peripheral blood leukocyte expression level of lncRNA steroid receptor RNA
      activator (SRA) and its association with polycystic ovary syndrome: a case
      control study.
AB  - Polycystic ovary syndrome (PCOS) has been recognized as a common reproductive and
      endocrine disorder. Long noncoding RNA (lncRNA) steroid receptor RNA activator
      (SRA) affects multiple biological processes. However, it is not known whether
      lncRNA SRA is associated with PCOS. In the study, we measured the expression
      level of lncRNA SRA in PCOS patients, and analyzed the association between lncRNA
      SRA and multiple key endocrine parameters of PCOS. LncRNA SRA expression was
      significantly higher in the women with PCOS than that in the controls. There was
      a significant positive correlation between lncRNA SRA expression and BMI in PCOS
      group. Furthermore, obesity positively associates with the high expression of
      lncRNA SRA in PCOS women but without the association in control women. In
      conclusion, we found that the lncRNA SRA expression is potentially associated
      with PCOS and it has positive correlation with obesity in PCOS, thereby
      suggesting that elevated lncRNA SRA might be an important mediator in adiposity
      related processes in PCOS for susceptible individuals. 

PMID- 25609052
TI  - High sensitivity cardiac troponin and the under-diagnosis of myocardial
      infarction in women: prospective cohort study.
AB  - OBJECTIVE: To evaluate the diagnosis of myocardial infarction using a high
      sensitivity troponin I assay and sex specific diagnostic thresholds in men and
      women with suspected acute coronary syndrome. DESIGN: Prospective cohort study.
      SETTING: Regional cardiac centre, United Kingdom. PARTICIPANTS: Consecutive
      patients with suspected acute coronary syndrome (n=1126, 46% women). Two
      cardiologists independently adjudicated the diagnosis of myocardial infarction by
      using a high sensitivity troponin I assay with sex specific diagnostic thresholds
      (men 34 ng/L, women 16 ng/L) and compared with current practice where a
      contemporary assay (50 ng/L, single threshold) was used to guide care. MAIN
      OUTCOME MEASURE: Diagnosis of myocardial infarction. RESULTS: The high
      sensitivity troponin I assay noticeably increased the diagnosis of myocardial
      infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men
      (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a
      cardiologist or undergo coronary revascularisation (P<0.05 for both). At 12
      months, women with undisclosed increases in troponin concentration (17-49 ng/L)
      and those with myocardial infarction (>=50 ng/L) had the highest rate of death or
      reinfarction compared with women without (<=16 ng/L) myocardial infarction (25%,
      24%, and 4%, respectively; P<0.001). CONCLUSIONS: Although having little effect
      in men, a high sensitivity troponin assay with sex specific diagnostic thresholds
      may double the diagnosis of myocardial infarction in women and identify those at
      high risk of reinfarction and death. Whether use of sex specific diagnostic
      thresholds will improve outcomes and tackle inequalities in the treatment of
      women with suspected acute coronary syndrome requires urgent attention.

PMID- 25609054
TI  - Early ultrasonographic evaluation of idiopathic clubfeet treated with
      manipulations, casts, and Botox((r)): a double-blind randomized control trial.
AB  - BACKGROUND: The manipulations, casts, and Botox((r)) method for treating
      idiopathic clubfoot is an alternative non-surgical treatment method. Botox((r))
      induced reversible muscle paralysis of the gastrocsoleus enables a physician to
      manipulate and cast the clubfoot in greater dorsiflexion. Ultrasound is
      incorporated during the early treatment stages to monitor the underlying
      physiology of the muscle-tendon unit following Botox((r)). METHODS:
      Ultrasonographic evaluation was performed parallel to a double-blind randomized
      control trial administering Botox((r)) or placebo to correct clubfoot. Patients
      underwent two-dimensional ultrasound to monitor the length changes to the
      gastrocsoleus and Achilles tendon unit at two time points: pre-injection
      (baseline) and 6 weeks post-blinded injection. Gastrocsoleus and Achilles tendon
      length measurements were analyzed among placebo, Botox((r)) and contralateral
      controls using repeated measures ANOVA. RESULTS: The baseline gastrocsoleus
      length of the clubfoot (322.4 pixels) before blinded injection appears shorter
      than controls (337.5 pixels), but fails to reach significance (p = 0.05). The
      complex length within each of the three treatment groups displayed no significant
      change between baseline and 6 weeks. The complex-tendon ratio and muscle-tendon
      ratio of the Botox((r)) treatment group was significantly decreased compared to
      controls (p = 0.049 and 0.042, respectively). Briefly, when expressed as a
      proportion, an increase in Achilles tendon length and decrease in gastrocsoleus
      is observed when clubfeet are treated with Botox((r)). CONCLUSIONS: Only in the
      Botox((r)) treatment cohort did the muscle shrink to uncover tendon (seen as a
      decreased complex-tendon ratio and muscle-tendon ratio) over the 6-week interval
      to effectively increase tendon length with respect to the unit as a whole.

PMID- 25609055
TI  - Nannofossils in 2011 El Hierro eruptive products reinstate plume model for Canary
      Islands.
AB  - The origin and life cycle of ocean islands have been debated since the early days
      of Geology. In the case of the Canary archipelago, its proximity to the Atlas
      orogen led to initial fracture-controlled models for island genesis, while later
      workers cited a Miocene-Quaternary east-west age-progression to support an
      underlying mantle-plume. The recent discovery of submarine Cretaceous volcanic
      rocks near the westernmost island of El Hierro now questions this systematic age
      progression within the archipelago. If a mantle-plume is indeed responsible for
      the Canaries, the onshore volcanic age-progression should be complemented by
      progressively younger pre-island sedimentary strata towards the west, however,
      direct age constraints for the westernmost pre-island sediments are lacking. Here
      we report on new age data obtained from calcareous nannofossils in sedimentary
      xenoliths erupted during the 2011 El Hierro events, which date the sub-island
      sedimentary rocks to between late Cretaceous and Pliocene in age. This age-range
      includes substantially younger pre-volcanic sedimentary rocks than the Jurassic
      to Miocene strata known from the older eastern islands and now reinstate the
      mantle-plume hypothesis as the most plausible explanation for Canary volcanism.
      The recently discovered Cretaceous submarine volcanic rocks in the region are, in
      turn, part of an older, fracture-related tectonic episode. 

PMID- 25609056
TI  - Presentation and treatment of uterine leiomyoma in adolescence: a systematic
      review.
AB  - BACKGROUND: Uterine leiomyoma is the most common gynecological tumor in the
      reproductive years. However, it is extremely rare in adolescence (<1%), with few
      reports found in the literature. The biological behavior of such tumors in this
      age group is unknown, as well as the best possible treatment for this population.
      We aimed to analyze all available reports of uterine leiomyoma in adolescence.
      METHODS: A systematic review was performed at PubMed/MEDLINE and EMBASE. Between
      1965 and 2014, 19 reports were found on uterine leiomyoma in patients under 18
      years. The following parameters were discussed: age, tumor diameter, symptoms,
      clinical treatments, surgical treatments, hemodynamic changes. RESULTS: Mean age
      was 15.35 (14-17) years. Mean tumor diameter was 12.28 cm (3-30) and median
      diameter was 10 cm. Most patients presented with symptoms (87.5%), including
      abnormal uterine bleeding (10/18) and pelvic/abdominal pain (6/18). A pelvic mass
      was the most common finding. Two patients required transfusion due to anemia. One
      patient underwent abdominal hysterectomy, and the others underwent myomectomy.
      Mean follow-up was 1 year and 8 months, and only case recurred, after 6 months.
      CONCLUSION: Leiomyomas' biologic behavior in adolescents may be different from
      that of older women, but their molecular characteristics still haven't been
      analyzed. Optimal treatment is still not defined, but myomectomy has several
      advantages in this population. Leiomyomas must be remembered as an important
      differential diagnosis of pelvic mass in adolescents.

PMID- 25609057
TI  - A medium density genetic map and QTL for behavioral and production traits in
      Japanese quail.
AB  - BACKGROUND: Behavioral traits such as sociability, emotional reactivity and
      aggressiveness are major factors in animal adaptation to breeding conditions. In
      order to investigate the genetic control of these traits as well as their
      relationships with production traits, a study was undertaken on a large second
      generation cross (F2) between two lines of Japanese Quail divergently selected on
      their social reinstatement behavior. All the birds were measured for several
      social behaviors (social reinstatement, response to social isolation, sexual
      motivation, aggression), behaviors measuring the emotional reactivity of the
      birds (reaction to an unknown object, tonic immobility reaction), and production
      traits (body weight and egg production). RESULTS: We report the results of the
      first genome-wide QTL detection based on a medium density SNP panel obtained from
      whole genome sequencing of a pool of individuals from each divergent line. A
      genetic map was constructed using 2145 markers among which 1479 could be
      positioned on 28 different linkage groups. The sex-averaged linkage map spanned a
      total of 3057 cM with an average marker spacing of 2.1 cM. With the exception of
      a few regions, the marker order was the same in Japanese Quail and the chicken,
      which confirmed a well conserved synteny between the two species. The linkage
      analyses performed using QTLMAP software revealed a total of 45 QTLs related
      either to behavioral (23) or production (22) traits. The most numerous QTLs (15)
      concerned social motivation traits. Interestingly, our results pinpointed
      putative pleiotropic regions which controlled emotional reactivity and body
      weight of birds (on CJA5 and CJA8) or their social motivation and the onset of
      egg laying (on CJA19). CONCLUSION: This study identified several QTL regions for
      social and emotional behaviors in the Quail. Further research will be needed to
      refine the QTL and confirm or refute the role of candidate genes, which were
      suggested by bioinformatics analysis. It can be hoped that the identification of
      genes and polymorphisms related to behavioral traits in the quail will have
      further applications for other poultry species (especially the chicken) and will
      contribute to solving animal welfare issues in poultry production.

PMID- 25609058
TI  - DNMT3A Mutational Status Affects the Results of Dose-Escalated Induction Therapy
      in Acute Myelogenous Leukemia.
AB  - PURPOSE: DNA methyltransferase 3A (DNMT3A) is one of the commonly mutated genes
      in acute myelogenous leukemia (AML). Reports on the prognostic significance of
      DNMT3A mutations have been inconsistent, and most of the data are available only
      for patients 60 years of age or younger. We hypothesized that this inconsistency
      is due to an interaction between the dose of anthracycline used in induction
      therapy and DNMT3A status. We studied whether patients with DNMT3A-mutated AML
      treated with standard dose anthracyclines had an inferior survival compared with
      patients with other mutation profiles or those who received high-dose therapy.
      EXPERIMENTAL DESIGN: A total of 152 patients in this retrospective cohort study
      (median age, 54 years) with de novo AML underwent induction therapy and next
      generation sequencing of 33 commonly mutated genes in hematologic malignancies,
      including DNMT3A, FLT3-ITD, NPM1, and IDH1/2. Cox regression was used to know
      whether those with DNMT3A mutations who were treated with standard dose
      anthracycline had inferior survival. RESULTS: DNMT3A mutations, found in 32% of
      patients, were not associated with an inferior survival. Dose escalation of
      anthracycline in the induction regimen was associated with improved survival in
      those with DNMT3A mutations but not those with wild-type DNMT3A. Patients with
      DNMT3A mutations who received standard dose induction had shorter survival time
      than other patient groups (10.1 months vs. 19.8 months, P = 0.0129). This
      relationship remained significant (HR, 1.90; P = 0.006) controlling for multiple
      variables. CONCLUSIONS: Patients with DNMT3A-mutated AML have an inferior
      survival when treated with standard-dose anthracycline induction therapy. This
      group should be considered for high-dose induction therapy.

PMID- 25609059
TI  - Trabectedin efficacy in Ewing sarcoma is greatly increased by combination with
      anti-IGF signaling agents.
AB  - PURPOSE: Goal of this study was to identify mechanisms that limit efficacy of
      trabectedin (ET-743, Yondelis) in Ewing sarcoma (EWS), so as to develop a
      clinical applicable combination therapy. EXPERIMENTAL DESIGN: By chromatin
      immunoprecipitation, we analyzed EWS-FLI1 binding to the promoters of several
      target genes, such as TGFbetaR2, CD99, insulin-like growth factor receptor 1
      (IGF1R), and IGF1, both in vitro and in xenografts treated with trabectedin or
      doxorubicin. Combined therapy with trabectedin and anti-IGF1R agents (AVE1642
      HAb; OSI-906) was tested in vitro and in xenografts. RESULTS: We confirm that
      both trabectedin and doxorubicin were able to strongly reduce EWS-FLI1 (both type
      I and type II) binding to two representative target genes (TGFbetaR2 and CD99),
      both in vitro and in xenografts. However, trabectedin, but not doxorubicin, was
      also able to increase the occupancy of EWS-FLI1 to IGF1R promoters, leading to
      IGF1R upregulation. Inhibition of IGF1R either by the specific AVE1642 human
      antibody or by the dual IGF1R/insulin receptor inhibitor OSI-906 (Linsitinib)
      greatly potentiate the efficacy of trabectedin in the 13 EWS cell lines here
      considered as well as in TC-71 and 6647 xenografts. Combined therapy induced
      synergistic cytotoxic effects. Trabectedin and OSI-906 deliver complementary
      messages that likely converge on DNA-damage response and repair pathways.
      CONCLUSIONS: We showed that trabectedin may not only inhibit but also enhance the
      binding of EWS-FLI1 to certain target genes, leading to upregulation of IGF1R. We
      here provide the rationale for combining trabectedin to anti-IGF1R inhibitors.

PMID- 25609061
TI  - Association of antigen-specific T-cell responses with antigen expression and
      immunoparalysis in multiple myeloma.
AB  - PURPOSE: Cancer testis antigens (CTA) are immunotherapeutical targets aberrantly
      expressed on multiple myeloma cells, especially at later stages, when a
      concomitant immunoparesis hampers vaccination approaches. EXPERIMENTAL DESIGN: We
      assessed the expression of the multiple myeloma antigen HM1.24 (reported present
      in all malignant plasma cells) and the CTAs MAGE-A2/A3 and NY-ESO-1 (aberrantly
      expressed in a subset of patients with myeloma), in CD138-purified myeloma cells
      by qRT-PCR (n = 149). In a next step, we analyzed the antigen-specific T-cell
      responses against these antigens by IFNgamma EliSpot assay (n = 145) and
      granzymeB ELISA (n = 62) in relation to stage (tumor load) and expression of the
      respective antigen. RESULTS: HM1.24 is expressed in all plasma-cell samples,
      whereas CTAs are significantly more frequent in later stages. HM1.24-specific T
      cell responses, representing the immunologic status, significantly decreased from
      healthy donors to advanced disease. For the CTAs, the probability of T-cell
      responses increased in early and advanced stages compared with healthy donors,
      paralleling increased probability of expression. In advanced stages, T-cell
      responses decreased because of immunoparesis. CONCLUSION: In conclusion, specific
      T-cell responses in myeloma are triggered by antigen expression but suppressed by
      tumor load. Future CTA-based immunotherapeutical approaches might target early
      plasma-cell diseases to establish prophylactically a specific T-cell response
      against late-stage antigens in immunocompetent patients.

PMID- 25609060
TI  - Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-type
      Glioma.
AB  - PURPOSE: Oncogenic fusions consisting of fibroblast growth factor receptor (FGFR)
      and TACC are present in a subgroup of glioblastoma (GBM) and other human cancers
      and have been proposed as new therapeutic targets. We analyzed frequency and
      molecular features of FGFR-TACC fusions and explored the therapeutic efficacy of
      inhibiting FGFR kinase in GBM and grade II and III glioma. EXPERIMENTAL DESIGN:
      Overall, 795 gliomas (584 GBM, 85 grades II and III with wild-type and 126 with
      IDH1/2 mutation) were screened for FGFR-TACC breakpoints and associated molecular
      profile. We also analyzed expression of the FGFR3 and TACC3 components of the
      fusions. The effects of the specific FGFR inhibitor JNJ-42756493 for FGFR3-TACC3
      positive glioma were determined in preclinical experiments. Two patients with
      advanced FGFR3-TACC3-positive GBM received JNJ-42756493 and were assessed for
      therapeutic response. RESULTS: Three of 85 IDH1/2 wild-type (3.5%) but none of
      126 IDH1/2-mutant grade II and III gliomas harbored FGFR3-TACC3 fusions. FGFR
      TACC rearrangements were present in 17 of 584 GBM (2.9%). FGFR3-TACC3 fusions
      were associated with strong and homogeneous FGFR3 immunostaining. They are
      mutually exclusive with IDH1/2 mutations and EGFR amplification, whereas they co
      occur with CDK4 amplification. JNJ-42756493 inhibited growth of glioma cells
      harboring FGFR3-TACC3 in vitro and in vivo. The two patients with FGFR3-TACC3
      rearrangements who received JNJ-42756493 manifested clinical improvement with
      stable disease and minor response, respectively. CONCLUSIONS: RT-PCR sequencing
      is a sensitive and specific method to identify FGFR-TACC-positive patients. FGFR3
      TACC3 fusions are associated with uniform intratumor expression of the fusion
      protein. The clinical response observed in the FGFR3-TACC3-positive patients
      treated with an FGFR inhibitor supports clinical studies of FGFR inhibition in
      FGFR-TACC-positive patients.

PMID- 25609062
TI  - Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor
      Sensitivity in Fanconi Anemia Head and Neck Cancers.
AB  - PURPOSE: Fanconi anemia is an inherited disorder associated with a constitutional
      defect in the Fanconi anemia DNA repair machinery that is essential for
      resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are
      predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a
      young age. Prognosis is poor, partly due to patient intolerance of chemotherapy
      and radiation requiring dose reduction, which may lead to early recurrence of
      disease. EXPERIMENTAL DESIGN: Using HNSCC cell lines derived from the tumors of
      patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors
      of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent
      chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter
      assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous
      end joining (NHEJ). RESULTS: Surprisingly, interstrand crosslinker (ICL)
      sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell
      systems. Our results suggest that the increased Ku-dependent NHEJ that is
      expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL
      exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi
      anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells
      were sensitive to PARP inhibition, and sensitivity of human cells was attenuated
      by Fanconi anemia gene complementation. CONCLUSIONS: The observed reliance upon
      PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can
      acquire relative resistance to the ICL-based chemotherapy that is a foundation of
      HNSCC treatment, as well as a potential target for overcoming chemoresistance in
      the chemosensitive individual.

PMID- 25609063
TI  - The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited
      by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma.
AB  - PURPOSE: Wee1 regulates key DNA damage checkpoints, and in this study, the
      efficacy of the Wee1 inhibitor MK-1775 was evaluated in glioblastoma multiforme
      (GBM) xenograft models alone and in combination with radiation and/or
      temozolomide. EXPERIMENTAL DESIGN: In vitro MK-1775 efficacy alone and in
      combination with temozolomide, and the impact on DNA damage, was analyzed by
      Western blotting and gammaH2AX foci formation. In vivo efficacy was evaluated in
      orthotopic and heterotopic xenografts. Drug distribution was assessed by
      conventional mass spectrometry (MS) and matrix-assisted laser
      desorption/ionization (MALDI)-MS imaging. RESULTS: GBM22 (IC50 = 68 nmol/L) was
      significantly more sensitive to MK-1775 compared with five other GBM xenograft
      lines, including GBM6 (IC50 >300 nmol/L), and this was associated with a
      significant difference in pan-nuclear gammaH2AX staining between treated GBM22
      (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no
      sensitizing effect of MK-1775 when combined with temozolomide in vitro. In an
      orthotopic GBM22 model, MK-1775 was ineffective when combined with temozolomide,
      whereas in a flank model of GBM22, MK-1775 exhibited both single-agent and
      combinatorial activity with temozolomide. Consistent with limited drug delivery
      into orthotopic tumors, the normal brain to whole blood ratio following a single
      MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly
      lower MK-1775 distribution in orthotopic as compared with heterotopic GBM22
      tumors. CONCLUSIONS: Limited distribution to brain tumors may limit the efficacy
      of MK-1775 in GBM.

PMID- 25609064
TI  - PD-L1 Expression and Tumor-Infiltrating Lymphocytes Define Different Subsets of
      MAPK Inhibitor-Treated Melanoma Patients.
AB  - PURPOSE: To evaluate the expression of tumor PD-L1 and changes in tumor
      infiltrating lymphocyte (TIL) populations in patients with metastatic melanoma
      treated with targeted MAPK inhibitors. EXPERIMENTAL DESIGN: Ninety-three tumors
      were analyzed from 40 patients treated with a BRAF inhibitor alone (BRAFi; n =
      28) or combination of BRAF and MEK inhibitors (Combi; n = 12). Tumors were
      excised before treatment (PRE), early during treatment (EDT), and at progression
      (PROG). Immunohistochemical staining was performed for CD4, CD8, CD68, FOXP3,
      LAG3, PD-1, and PD-L1 and correlated with clinical outcome. RESULTS: Patients'
      tumors that were PD-L1 positive at baseline showed a significant decrease in PD
      L1 expression at PROG (P = 0.028), whereas patients' tumors that were PD-L1
      negative at baseline showed a significant increase in PD-L1 expression at PROG (P
      = 0.008) irrespective of treatment with BRAFi or Combi. Overall PD-L1 expression
      highly correlated with TIL immune markers. BRAFi-treated patients showed
      significant increases in CD4(+), CD8(+), and PD-1(+) lymphocytes from PRE to EDT
      (P = 0.001, P = 0.001, P = 0.017, respectively), and Combi-treated patients
      showed similar increases in CD4(+) and CD8(+) lymphocytes from PRE to EDT (P =
      0.017, P = 0.021). CONCLUSIONS: The addition of MEKi to BRAFi did not result in
      significant reduction in immune infiltration in EDT biopsies. This provides
      support for conducting trials that combine MAPKi with immune checkpoint
      inhibitors in the hope of improving complete and durable response rates. PD-L1
      expression at PROG on MAPK inhibitors varied according to baseline expression
      suggesting that combining MAPKi with immunotherapies concurrently may be more
      effective in patients with PD-L1 expression and TILs in baseline melanoma
      samples.

PMID- 25609065
TI  - "To B(MP-2) or Not To B(MP-2)" or "Much Ado About Nothing": Are Orthobiologics in
      Tumor Surgery Worth the Risks?
AB  - Geller and colleagues report that adjuvant chemotherapy affected the adequacy of
      osteosarcoma local surgical control. Exogenous bone morphogenetic protein-2 (BMP
      2) did not increase local recurrence, but the limited theoretical benefits of BMP
      2 for a subset of patients with osteosarcoma may not justify the systemic and
      long-term risks.

PMID- 25609066
TI  - Cyclin-dependent kinase 5 decreases in gastric cancer and its nuclear
      accumulation suppresses gastric tumorigenesis.
AB  - PURPOSE: As a cyclin-independent atypical CDK, the role of CDK5 in regulating
      cell proliferation in gastric cancer remains unknown. EXPERIMENTAL DESIGN:
      Expression of CDK5 in gastric tumor and paired adjacent noncancerous tissues from
      437 patients was measured by Western blotting, immunohistochemistry, and real
      time PCR. The subcellular translocation of CDK5 was monitored during gastric
      cancer cell proliferation. The role of nuclear CDK5 in gastric cancer tumorigenic
      proliferation and ex vivo xenografts was explored. Furthermore, by screening for
      compounds in the PubChem database that disrupt CDK5 association with its nuclear
      export facilitator, we identified a small molecular (NS-0011) that inhibits
      gastric cancer cell growth. RESULTS: CDK5 level was significantly decreased in
      the majority of gastric tumor tissues, and the reduction of CDK5 correlated with
      the severity of gastric cancer based on tumor and lymph node metastasis and
      patient 5-year fatality rate. Nuclear localization of CDK5 was found to be
      significantly decreased in tumor tissues and gastric cancer cell lines, whereas
      exogenously expression of nucleus-targeted CDK5 inhibited the proliferation and
      xenograft implantation of gastric cancer cells. Treatment with the small molecule
      NS-0011, which increases CDK5 accumulation in the nucleus, suppressed both cancer
      cell proliferation and xenograft tumorigenesis. CONCLUSIONS: Our results suggest
      that low CDK5 expression is associated with poor overall survival in patients
      with gastric cancer, and nuclear accumulation of CDK5 inhibits the proliferation
      and tumorigenicity of human gastric cancer cells.

PMID- 25609067
TI  - Integrating RAS status into prognostic signatures for adenocarcinomas of the
      lung.
AB  - PURPOSE: While the dysregulation of specific pathways in cancer influences both
      treatment response and outcome, few current prognostic markers explicitly
      consider differential pathway activation. Here we explore this concept, focusing
      on K-Ras mutations in lung adenocarcinoma (present in 25%-35% of patients).
      EXPERIMENTAL DESIGN: The effect of K-Ras mutation status on prognostic accuracy
      of existing signatures was evaluated in 404 patients. Genes associated with K-Ras
      mutation status were identified and used to create a RAS pathway activation
      classifier to provide a more accurate measure of RAS pathway status. Next, 8
      million random signatures were evaluated to assess differences in prognosing
      patients with or without RAS activation. Finally, a prognostic signature was
      created to target patients with RAS pathway activation. RESULTS: We first show
      that K-Ras status influences the accuracy of existing prognostic signatures,
      which are effective in K-Ras-wild-type patients but fail in patients with K-Ras
      mutations. Next, we show that it is fundamentally more difficult to predict the
      outcome of patients with RAS activation (RAS(mt)) than that of those without
      (RAS(wt)). More importantly, we demonstrate that different signatures are
      prognostic in RAS(wt) and RAS(mt). Finally, to exploit this discovery, we create
      separate prognostic signatures for RAS(wt) and RAS(mt) patients and show that
      combining them significantly improves predictions of patient outcome.
      CONCLUSIONS: We present a nested model for integrated genomic and transcriptomic
      data. This model is general and is not limited to lung adenocarcinomas but can be
      expanded to other tumor types and oncogenes.

PMID- 25609069
TI  - HER Targeting in HER2-Negative Breast Cancers: Looking for the HER3 Positive.
AB  - Targeting HER2 for the treatment of HER2-positive breast cancers is now a
      validated treatment paradigm. However, evidence suggests that this family of
      receptors may have important roles outside of the realm of HER2 amplification.
      There is considerable interest in the development of biomarkers to identify such
      breast cancers.

PMID- 25609070
TI  - Kidney lite: four doctors with only four kidneys.

PMID- 25609068
TI  - Pharmacodynamic imaging guides dosing of a selective estrogen receptor degrader.
AB  - PURPOSE: Estrogen receptor (ER) targeting is key in management of receptor
      positive breast cancer. Currently, there are no methods to optimize anti-ER
      therapy dosing. This study assesses the use of 16alpha-(18)F-fluoroestradiol
      ((18)F-FES) PET for fulvestrant dose optimization in a preclinical ER(+) breast
      cancer model. EXPERIMENTAL DESIGN: In vitro, (18)F-FES retention was compared
      with ERalpha protein expression (ELISA) and ESR1 mRNA transcription (qPCR) in
      MCF7 cells (ER(+)) after treatment with different fulvestrant doses. MCF7
      xenografts were grown in ovariectomized nude mice and assigned to vehicle, low-
      (0.05 mg), medium- (0.5 mg), or high-dose (5 mg) fulvestrant treatment groups (5
      7 per group). Two and 3 days after fulvestrant treatment, PET/CT was performed
      using (18)F-FES and (18)F-FDG, respectively. ER expression was assessed by
      immunohistochemistry, ELISA, and qPCR on xenografts. Tumor proliferation was
      assessed using Ki67 immunohistochemistry. RESULTS: In vitro, we observed a
      parallel graded reduction in (18)F-FES uptake and ER expression with increased
      fulvestrant doses, despite enhancement of ER mRNA transcription. In xenografts,
      ER expression significantly decreased with increased fulvestrant dose, despite
      similar mRNA expression and Ki67 staining among the treatment groups. We observed
      a significant dose-dependent reduction of (18)F-FES PET mean standardized uptake
      value (SUV(mean)) with fulvestrant treatment but no significant difference among
      the treatment groups in (18)F-FDG PET SUV(mean). CONCLUSIONS: We demonstrated
      that (18)F-FES uptake mirrors the dose-dependent changes in functional ER
      expression with fulvestrant resulting in ER degradation and/or blockade; these
      precede changes in tumor metabolism and proliferation. Quantitative (18)F-FES PET
      may be useful for tracking early efficacy of ER blockade/degradation and guiding
      ER-targeted therapy dosing in patients with breast cancer.

PMID- 25609072
TI  - Knockdown of telomeric repeat binding factor 2 enhances tumor radiosensitivity
      regardless of telomerase status.
AB  - PURPOSE: To investigate the effects of TRF2 depletion on radiosensitivity in both
      the telomerase-positive cell lines (A549) and alternative lengthening of telomere
      (ALT) cell lines (U2OS). METHODS: X-ray irradiation was used to establish two
      radioresistant cancer models (A549R and U2OSR) from A549 and U2OS. Colony
      formation assay was applied to examine the radiosensitivity of radioresistant
      A549R and U2OSR cells and TRF2 low-expression cells. Real-time PCR and TeloTAGGG
      Telomerase PCR ELISA Kit were performed to examine telomere length and telomerase
      activity separately. gamma-H2AX was detected by immunofluorescence to assess the
      radiation-induced DSBs. RESULTS: Radioresistant cancer models were established,
      in which TRF2 was significantly over-expressed. Low expression of TRF2 protein
      could enhance the radiosensitivity and induce telomere length of A549 and U2OS
      cell shortening. In A549 cells with TRF2 down-regulated, the telomerase activity
      was inhibited, too. TRF2 deficiency increases gamma-H2AX foci and fails to
      protect telomere from radiation. CONCLUSION: The data suggest that TRF2 is a
      radioresistant protein in A549 and U2OS cells, and could potentially be a target
      for radiosensitization of both telomerase-positive and ALT cells in radiotherapy.

PMID- 25609071
TI  - Early white matter abnormalities, progressive brain pathology and motor deficits
      in a novel knock-in mouse model of Huntington's disease.
AB  - White matter abnormalities have been reported in premanifest Huntington's disease
      (HD) subjects before overt striatal neuronal loss, but whether the white matter
      changes represent a necessary step towards further pathology and the underlying
      mechanism of these changes remains unknown. Here, we characterized a novel knock
      in mouse model that expresses mouse HD gene homolog (Hdh) with extended CAG
      repeat- HdhQ250, which was derived from the selective breeding of HdhQ150 mice.
      HdhQ250 mice manifest an accelerated and robust phenotype compared with its
      parent line. HdhQ250 mice exhibit progressive motor deficits, reduction in
      striatal and cortical volume, accumulation of mutant huntingtin aggregation,
      decreased levels of DARPP32 and BDNF and altered striatal metabolites. The
      abnormalities detected in this mouse model are reminiscent of several aspects of
      human HD. In addition, disturbed myelination was evident in postnatal Day 14
      HdhQ250 mouse brain, including reduced levels of myelin regulatory factor and
      myelin basic protein, and decreased numbers of myelinated axons in the corpus
      callosum. Thinner myelin sheaths, indicated by increased G-ratio of myelin, were
      also detected in the corpus callosum of adult HdhQ250 mice. Moreover,
      proliferation of oligodendrocyte precursor cells is altered by mutant huntingtin
      both in vitro and in vivo. Our data indicate that this model is suitable for
      understanding comprehensive pathogenesis of HD in white matter and gray matter as
      well as developing therapeutics for HD. 

PMID- 25609073
TI  - In vitro and in vivo antitumor activity of a novel porphyrin-based
      photosensitizer for photodynamic therapy.
AB  - PURPOSE: Photodynamic therapy (PDT) is a promising treatment in cancer therapy,
      based on the use of a photosensitizer activated by visible light in the presence
      of oxygen. Nowadays significant research efforts have been focused on finding a
      new photosensitizer. In the present paper, the antitumor effects of a novel
      porphyrin-based photosensitizer, {Carboxymethyl-[2-(carboxymethyl-{[4-(10,15,20
      triphenylporphyrin-5-yl)-phenylcarbamoyl]-methyl}-amino)-ethyl]-amino}-acetic
      acid (ATPP-EDTA) on two types of human malignant tumor cells in vitro and a
      gastric cancer model in nude mice, were evaluated. METHODS: The PDT efficacy with
      ATPP-EDTA in vitro was assessed by MTT assay. The intracellular accumulation was
      detected with fluorescence spectrometer, and the intracellular distribution was
      determined by laser scanning confocal microscopy. The mode of cell death was
      investigated by Hoechst 33342 staining and flow cytometer. BGC823-derived
      xenograft tumor model was established to explore the in vivo antitumor effects of
      ATPP-EDTA. RESULTS: ATPP-EDTA exhibited intense phototoxicity on both cell lines
      in vitro in concentration- and light dose-dependent manners meanwhile imposing
      minimal dark cytotoxicity. The accumulation of ATPP-EDTA in two malignant cell
      lines was time-dependent and prior compared to normal cells. It was mainly
      localized at lysosomes, but induced cell death by apoptotic pathway. ATPP-EDTA
      significantly inhibited the growth of BGC823 tumors in nude mice (160 mW/cm(2),
      100 J/cm(2)). CONCLUSIONS: Present studies suggest that ATPP-EDTA is an effective
      photosensitizer for PDT to tumors. It distributed in lysosomes and caused cell
      apoptosis. ATPP-EDTA, as a novel photosensitizer, has a great potential for human
      gastric cancer treatment in PDT and deserves further investigations.

PMID- 25609074
TI  - Meningiomas after cranial radiotherapy for childhood cancer: a single institution
      experience.
AB  - PURPOSE: Childhood cancer survivors (CCS) treated with cranial radiation therapy
      (CRT) are at risk of developing meningiomas. The aim of this study was to
      evaluate the cumulative incidence of meningiomas in a cohort of CCS who
      previously underwent CRT. METHODS: We considered all CCS who received CRT and
      were followed up at the "Transition Unit for Childhood Cancer Survivors" in
      Turin. Even though asymptomatic, they had at least one brain computed tomography
      or magnetic resonance imaging performed at a minimum interval of 10 years after
      treatment for pediatric cancer. RESULTS: We identified 90 patients (median follow
      up 24.6 years). Fifteen patients developed meningioma (median time from pediatric
      cancer, 22.5 years). In four patients, it was suspected on the basis of
      neurological symptoms (i.e., headache or seizures), whereas all other cases,
      including five giant meningiomas, were discovered in otherwise asymptomatic
      patients. Multiple meningiomas were discovered in four CCS. Ten patients
      underwent surgical resection. An atypical meningioma (grade II WHO) was reported
      in four patients. One patient with multiple meningiomas died for a rapid growth
      of the intracranial lesions. A second neoplasm (SN) other than meningioma was
      diagnosed in five out of the 15 patients with meningioma and in ten out of the 75
      CCS without meningioma. Cox multivariate analysis showed that the occurrence of
      meningioma was associated with the development of other SNs, whereas age, sex, or
      CRT dose had no influence. CONCLUSIONS: CCS at risk of the development of
      meningioma deserve close clinical follow-up, especially those affected by other
      SNs.

PMID- 25609075
TI  - Vaccine self-assembling immune matrix is a new delivery platform that enhances
      immune responses to recombinant HBsAg in mice.
AB  - Vaccination remains the most effective public health tool to prevent infectious
      diseases. Many vaccines are marginally effective and need enhancement for
      immunocompromised, elderly, and very young populations. To enhance
      immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic
      oligopeptide to create VacSIM (vaccine self-assembling immune matrix), a new
      delivery method. VacSIM solution can easily be mixed with antigens, organisms,
      and adjuvants for injection. Postinjection, the peptides self-assemble into
      hydrated nanofiber gel matrices, forming a depot with antigens and adjuvants in
      the aqueous phase. We believe the depot provides slow release of immunogens,
      leading to increased activation of antigen-presenting cells that then drive
      enhanced immunogenicity. Using recombinant hepatitis B virus surface antigen
      (rHBsAg) as a model immunogen, we compared VacSIM delivery to delivery in alum or
      complete Freund's adjuvant (CFA). Delivery of the rHBsAg antigen to mice via
      VacSIM without adjuvant elicited higher specific IgG responses than when rHBsAg
      was delivered in alum or CFA. Evaluating IgG subtypes showed a mixed Th1/Th2 type
      response following immunization with VacSIM, which was driven further toward Th1
      with addition of CpG as the adjuvant. Increased specific IgG endpoint titers were
      observed in both C57BL/6 and BALB/c mice, representative of Th1 and Th2
      environments, respectively. Restimulation of splenocytes suggests that VacSIM
      does not cause an immediate proinflammatory response in the host. Overall, these
      results suggest that VacSIM, as a new delivery method, has the potential to
      enhance immunogenicity and efficacy of numerous vaccines. 

PMID- 25609076
TI  - Prediction of pathologic prognostic factors in patients with lung
      adenocarcinomas: comparison of thin-section computed tomography and positron
      emission tomography/computed tomography.
AB  - BACKGROUND: The ratio of the maximum diameter of consolidation to the maximum
      tumor diameter (C/T ratio) on thin-section computed tomography (TSCT) and the
      maximum standardized uptake value (SUVmax) on 18 F-fluorodeoxyglucose positron
      emission tomography/computed tomography (PET/CT) are often used as preoperative
      independent variables to evaluate the invasiveness of lung adenocarcinoma. We
      investigated the associations between these independent variables and pathologic
      invasiveness in pulmonary adenocarcinomas. METHODS: We selected patients with
      peripheral lung adenocarcinomas, definitively diagnosed by surgical resection,
      with diameters of <= 30 mm over a 4-year period ending in December 2010. The
      association between 3 independent variables (tumor size, SUVmax, and C/T ratio)
      and pathologic prognostic factors was evaluated using logistic analysis. RESULTS:
      We evaluated a total of 163 primary lung adenocarcinomas in 148 patients (93
      males and 55 females; age range: 34 to 84 years). Using multivariate logistic
      regression analysis, SUVmax and the C/T ratio were significantly associated with
      tumor invasiveness (odds ratio [OR] = 1.227; p = 0.025 and OR = 1.019; p = 0.008,
      respectively). Tumor size was not associated with invasiveness (OR = 1.003; p =
      0.925). For solid type adenocarcinomas, only SUVmax was significantly associated
      with invasiveness (OR = 1.558; p = 0.003). For subsolid type adenocarcinomas,
      only the C/T ratio was significantly associated with invasiveness (OR = 1.030; p
      = 0.009). CONCLUSIONS: Both the C/T ratio and the SUVmax are significantly
      correlated with pathologic invasiveness in patients with small lung
      adenocarcinomas, while there was a difference between the 2 evaluations. Solid
      type adenocarcinomas with SUVmax values of >= 4.4 and subsolid type
      adenocarcinomas with C/T ratio >= 53% were so highly invasive.

PMID- 25609077
TI  - Clinical presentation of a patient with SLC20A2 and THAP1 deletions: differential
      diagnosis of oromandibular dystonia.

PMID- 25609079
TI  - Early detection of maternal deaths in Senegal through household-based death
      notification integrating verbal and social autopsy: a community-level case study.
AB  - BACKGROUND: Reliable detection of maternal deaths is an essential prerequisite
      for successful diagnosis of barriers to care and formulation of relevant targeted
      interventions. In a community-level case study, the use of household-level
      surveillance in Senegal unveiled an apparent increase in maternal deaths, which
      triggered a rapid-cycle collaborative response to implement a multipronged set of
      quick-win and sustained interventions intended to improve quality care. METHODS:
      Part of a multi-country effort, the Millennium Villages Project is implementing a
      routine community-level information system in Senegal, able to detect maternal
      deaths in real-time and uncover clinical and social factors contributing to
      mortality. Within this geographically demarcated area of approximately 32 000
      inhabitants, with a well-structured health system with patient referral services,
      deaths were registered and notified by community health workers, followed by
      timely verbal and social autopsies. Using the Pathway to Survival conceptual
      framework, case analysis and mortality reviews were conducted for evaluation and
      quality improvement purposes. RESULTS: The estimated maternal mortality rates
      rose from 67/100000 births in 2009 (1 death), to 202/100000 births in 2010 (3
      deaths) and 392/100000 births (5 deaths) in 2011. Although absolute numbers of
      maternal deaths remained too small for robust statistical analysis, following
      verbal autopsy analyses in 2011, it became evident that an unexpectedly high
      proportion of maternal deaths were occurring at the referral hospital, mostly
      post-Caesarian section. Inadequate case management of post-partum haemorrhage at
      the referral hospital was the most frequently identified probable cause of death.
      A joint task team systematically identified several layers of inefficiencies,
      with a potential negative impact on a larger catchment area than the study
      community. CONCLUSIONS: In this study, routine community-based surveillance
      identified inefficiencies at a tertiary level of care. Community-level
      surveillance systems that include pregnancy, birth and death tracking through
      household visits by community health workers , combined with verbal and social
      autopsy can identify barriers within the continuum of maternal care. Use of
      mHealth data collection tools sensitive enough to detect small changes in
      community-level mortality trends in real-time, can facilitate rapid-cycle quality
      improvement interventions, particularly when associated with social
      accountability structures of mortality reviews.

PMID- 25609078
TI  - Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple
      myeloma cells: role of DNA damage response activation.
AB  - BACKGROUND: DNAX accessory molecule-1 (DNAM-1) is an activating receptor
      constitutively expressed by macrophages/dendritic cells and by T lymphocytes and
      Natural Killer (NK) cells, having an important role in anticancer responses; in
      this regard, combination therapies able to enhance the expression of DNAM-1
      ligands on tumor cells are of therapeutic interest. In this study, we
      investigated the effect of different nitric oxide (NO) donors on the expression
      of the DNAM-1 ligand Poliovirus Receptor/CD155 (PVR/CD155) in multiple myeloma
      (MM) cells. METHODS: Six MM cell lines, SKO-007(J3), U266, OPM-2, RPMI-8226, ARK
      and LP1 were used to investigate the activity of different nitric oxide donors
      [DETA-NO and the NO-releasing prodrugs NCX4040 (NO-aspirin) and JS-K] on the
      expression of PVR/CD155, using Flow Cytometry and Real-Time PCR. Western-blot and
      specific inhibitors were employed to investigate the role of soluble guanylyl
      cyclase/cGMP and activation of the DNA damage response (DDR). RESULTS: Our
      results indicate that increased levels of nitric oxide can upregulate PVR/CD155
      cell surface and mRNA expression in MM cells; in addition, exposure to nitric
      oxide donors renders myeloma cells more efficient to activate NK cell
      degranulation and enhances their ability to trigger NK cell-mediated
      cytotoxicity. We found that activation of the soluble guanylyl cyclase and
      increased cGMP concentrations by nitric oxide is not involved in the up
      regulation of ligand expression. On the contrary, treatment of MM cells with
      nitric oxide donors correlated with the activation of a DNA damage response
      pathway and inhibition of the ATM /ATR/Chk1/2 kinase activities by specific
      inhibitors significantly abrogates up-regulation. CONCLUSIONS: The present study
      provides evidence that regulation of the PVR/CD155 DNAM-1 ligand expression by
      nitric oxide may represent an additional immune-mediated mechanism and supports
      the anti-myeloma activity of nitric oxide donors.

PMID- 25609080
TI  - Successful en bloc resection of recurrent hepatocellular carcinoma directly
      invading the abdominal wall: a case report.
AB  - INTRODUCTION: Repeat hepatic resection has previously been reported as the most
      effective treatment for recurrence of intrahepatic carcinoma. To the best of our
      knowledge, en bloc resection of recurrent hepatocellular carcinoma directly
      invading the abdominal wall has not been previously reported. CASE PRESENTATION:
      In September 2012, a 64-year-old Chinese male patient was referred to our
      hospital because of primary hepatocellular carcinoma located in Couinaud's
      segments III and V. Our patient first had a hepatectomy of the liver. Ten months
      later, he presented with an abdominal wall mass and upper abdominal pain.
      Computed tomography and magnetic resonance imaging scans demonstrated a 10cm
      tumor in his left liver with extrahepatic metastases in his abdominal wall. It
      was determined that he had recurrent hepatocellular carcinoma associated with
      direct invasion into his abdominal wall. He had an en bloc left hepatectomy with
      resection of the tumor in his abdominal wall. A pathological examination of the
      resected specimen confirmed the diagnosis of hepatocellular carcinoma involving
      the abdominal wall. Disease-free margins of resection were achieved. Our
      patient's postoperative course was uneventful. Eight months after the last
      surgery, our patient died owing to recurrence and distal metastasis. CONCLUSION:
      Direct invasion of hepatocellular carcinoma into the abdominal wall is rarely
      encountered. Complete surgical resection should be considered in patients with an
      appropriate hepatic functional reserve, with consideration of the technical
      difficulty relating to tumor involvement with surrounding tissues.

PMID- 25609082
TI  - Exploring healthy eating among ethnic minority students using mobile technology:
      Feasibility and adherence.
AB  - Interventions aiming to help ethnically diverse emerging adults engage in healthy
      eating have had limited success. The aim of this study was to assess the
      feasibility of and adherence to an intervention capitalizing on mobile technology
      to improve healthy eating. Participants created an online photo food journal and
      received motivational text messages three times a day. Satisfaction with the
      intervention was assessed, as were control variables including depression and
      body dissatisfaction. In addition, weight and height were measured. Levels of
      adherence to the photo food journal were high with approximately two photos
      posted a day at baseline. However, adherence rates decreased over the course of
      the study. Body dissatisfaction positively predicted adherence, while body mass
      index negatively predicted study satisfaction. Mobile technology provides
      innovative avenues for healthy eating interventions. Such interventions appear
      acceptable and feasible for a short period; however, more work is required to
      evaluate their viability regarding long-term engagement.

PMID- 25609081
TI  - Factors related to health-related quality of life among Chinese psychiatrists:
      occupational stress and psychological capital.
AB  - BACKGROUND: Psychiatry has been considered as one of the most stressful medical
      specialities, and psychiatrists are likely to experience impaired health-related
      quality of life (HRQOL). However, few studies are available in regard to related
      factors of HRQOL among psychiatrists in China. This study aims to evaluate the
      condition of HRQOL of psychiatrists and explore its predictive factors,
      especially the effects of occupational stress and psychological capital. METHODS:
      A cross-sectional, multicenter survey was conducted among psychiatrists from
      different regions of Liaoning province, China, during August 2013-April 2014.
      Self-administrated questionnaires including the 36-item Short-Form Health Survey
      (SF-36), the Chinese version Psychological Capital Questionnaire, effort-reward
      imbalance (ERI) scale and participants' basic characteristics were distributed to
      500 psychiatrists from 10 psychiatric hospitals of 8 major cities in Liaoning
      province. Overall, 373 psychiatrists became our final research objects.
      Hierarchical multiple regression analysis (HMR) was performed to explore the
      predictors of psychiatrists' HRQOL. RESULTS: The mean (SD) scores of PCS and MCS
      among psychiatrists were 79.78 (16.55) and 71.50 (19.24) respectively. The mean
      (SD) of ERR were 0.777 (0.493), and 89 (23.9%) had ERR scores above 1 (ERR > 1).
      Hierarchical multiple regression analysis showed that, psychiatrists' basic
      characteristics that significant correlated with PCS and MCS were educational
      level, turnover intention, and exercise; age, weekly working hours were
      associated with MCS; psychiatrists' experienced occupational stress (both ERR and
      overcommitment), and PsyCap were significant predictors for PCS and MCS.
      CONCLUSIONS: Chinese psychiatrists experienced relatively good physical QOL but
      impaired mental QOL, and they experienced high level of occupational stress. For
      the sake of psychiatrists' HRQOL, the reduction of occupational stress should be
      implemented. The enhancement of PsyCap could be a new intervention strategy and
      should be paid attention to in improving HRQOL of psychiatrists. Proportionate
      occupational reward (money, esteem, career opportunities) to their high work
      demands, psychological counseling, and stress management courses should be
      provided to psychiatrists to improve their QOL. PsyCap, as a personal coping
      resource open to change, should be managed and developed among psychiatrists.

PMID- 25609083
TI  - Using the M/G/infinity queueing model to predict inpatient family medicine
      service census and resident workload.
AB  - The number and timing of unplanned admissions to inpatient teaching services
      vary. Recent changes to resident duty hours make it essential to maximize
      learning experiences and balance workload on these services. Queueing theory
      provides a mechanism for understanding and planning for the variations in
      admissions and daily census. Daily admissions, length of stay, and daily census
      were modeled for a teaching inpatient family medicine service over 46 months
      using an M/G/infinity queueing model. Q-Q plots and a Kolmogorov-Smirnov test
      were used to check the fit of actual data to the model. Admissions and daily
      census followed a Poisson distribution (lambda = 3.28 and lambda = 8.28,
      respectively), while length-of-stay followed a lognormal distribution (u = 0.49,
      sigma2 = 0.83). The M/G/infinity queueing model proved useful for predicting
      overflow admission frequency, defining expected resident workload in terms of
      patient-days, and determining hospital unit size requirements.

PMID- 25609084
TI  - Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA
      in growth-retarded mammalian cells.
AB  - MicroRNAs (miRNAs) are tiny posttranscriptional regulators of gene expression in
      metazoan cells, where activity and abundance of miRNAs are tightly controlled.
      Regulated turnover of these regulatory RNAs is important to optimize cellular
      response to external stimuli. We report that the stability of mature miRNAs
      increases inversely with cell proliferation, and the increased number of
      microribonucleoproteins (miRNPs) in growth-restricted mammalian cells are in turn
      associated with polysomes. This heightened association of miRNA with polysomes
      also elicits reduced degradation of target mRNAs and impaired extracellular
      export of miRNA via exosomes. Overall polysome sequestration contributes to an
      increase of cellular miRNA levels but without an increase in miRNA activity.
      Therefore miRNA activity and turnover can be controlled by subcellular
      distribution of miRNPs that may get differentially regulated as a function of
      cell growth in mammalian cells. 

PMID- 25609085
TI  - G protein betagamma subunits regulate cardiomyocyte hypertrophy through a
      perinuclear Golgi phosphatidylinositol 4-phosphate hydrolysis pathway.
AB  - We recently identified a novel GPCR-dependent pathway for regulation of cardiac
      hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P)
      hydrolysis by a specific isoform of phospholipase C (PLC), PLCepsilon, at the
      nuclear envelope. How stimuli are transmitted from cell surface GPCRs to
      activation of perinuclear PLCepsilon is not clear. Here we tested the role of G
      protein betagamma subunits. Gbetagamma inhibition blocked ET-1-stimulated Golgi
      PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gbetagamma at
      the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation.
      Translocation of Gbetagamma to the Golgi stimulated perinuclear Golgi PI4P
      depletion and nuclear PKD activation. Finally, blocking Gbetagamma at the Golgi
      or PM blocked ET-1-dependent cardiomyocyte hypertrophy. These data indicate that
      Gbetagamma regulation of the perinuclear Golgi PI4P pathway and a separate
      pathway at the PM is required for ET-1-stimulated hypertrophy, and the efficacy
      of Gbetagamma inhibition in preventing heart failure maybe due in part to its
      blocking both these pathways. 

PMID- 25609086
TI  - Regulation of nuclear-cytoplasmic shuttling and function of Family with sequence
      similarity 13, member A (Fam13a), by B56-containing PP2As and Akt.
AB  - Recent genome-wide association studies reveal that the FAM13A gene is associated
      with human lung function and a variety of lung diseases, including chronic
      obstructive pulmonary disease, asthma, lung cancer, and pulmonary fibrosis. The
      biological functions of Fam13a, however, have not been studied. In an effort to
      identify novel substrates of B56-containing PP2As, we found that B56-containing
      PP2As and Akt act antagonistically to control reversible phosphorylation of
      Fam13a on Ser-322. We show that Ser-322 phosphorylation acts as a molecular
      switch to control the subcellular distribution of Fam13a. Fam13a shuttles between
      the nucleus and cytoplasm. When Ser-322 is phosphorylated by Akt, the binding
      between Fam13a and 14-3-3 is enhanced, leading to cytoplasmic sequestration of
      Fam13a. B56-containing PP2As dephosphorylate phospho-Ser-322 and promote nuclear
      localization of Fam13a. We generated Fam13a-knockout mice. Fam13a-mutant mice are
      viable and healthy, indicating that Fam13a is dispensable for embryonic
      development and physiological functions in adult animals. Intriguingly, Fam13a
      has the ability to activate the Wnt pathway. Although Wnt signaling remains
      largely normal in Fam13a-knockout lungs, depletion of Fam13a in human lung cancer
      cells causes an obvious reduction in Wnt signaling activity. Our work provides
      important clues to elucidating the mechanism by which Fam13a may contribute to
      human lung diseases. 

PMID- 25609087
TI  - Dendritic and axonal mechanisms of Ca2+ elevation impair BDNF transport in Abeta
      oligomer-treated hippocampal neurons.
AB  - Disruption of fast axonal transport (FAT) and intracellular Ca(2+) dysregulation
      are early pathological events in Alzheimer's disease (AD). Amyloid-beta oligomers
      (AbetaOs), a causative agent of AD, impair transport of BDNF independent of tau
      by nonexcitotoxic activation of calcineurin (CaN). Ca(2+)-dependent mechanisms
      that regulate the onset, severity, and spatiotemporal progression of BDNF
      transport defects from dendritic and axonal AbetaO binding sites are unknown.
      Here we show that BDNF transport defects in dendrites and axons are induced
      simultaneously but exhibit different rates of decline. The spatiotemporal
      progression of FAT impairment correlates with Ca(2+) elevation and CaN activation
      first in dendrites and subsequently in axons. Although many axonal pathologies
      have been described in AD, studies have primarily focused only on the dendritic
      effects of AbetaOs despite compelling reports of presynaptic AbetaOs in AD models
      and patients. Indeed, we observe that dendritic CaN activation converges on
      Ca(2+) influx through axonal voltage-gated Ca(2+) channels to impair FAT.
      Finally, FAT defects are prevented by dantrolene, a clinical compound that
      reduces Ca(2+) release from the ER. This work establishes a novel role for Ca(2+)
      dysregulation in BDNF transport disruption and tau-independent Abeta toxicity in
      early AD. 

PMID- 25609088
TI  - Increased water flux induced by an aquaporin-1/carbonic anhydrase II interaction.
AB  - Aquaporin-1 (AQP1) enables greatly enhanced water flux across plasma membranes.
      The cytosolic carboxy terminus of AQP1 has two acidic motifs homologous to known
      carbonic anhydrase II (CAII) binding sequences. CAII colocalizes with AQP1 in the
      renal proximal tubule. Expression of AQP1 with CAII in Xenopus oocytes or
      mammalian cells increased water flux relative to AQP1 expression alone. This
      required the amino-terminal sequence of CAII, a region that binds other transport
      proteins. Expression of catalytically inactive CAII failed to increase water flux
      through AQP1. Proximity ligation assays revealed close association of CAII and
      AQP1, an effect requiring the second acidic cluster of AQP1. This motif was also
      necessary for CAII to increase AQP1-mediated water flux. Red blood cell ghosts
      resealed with CAII demonstrated increased osmotic water permeability compared
      with ghosts resealed with albumin. Water flux across renal cortical membrane
      vesicles, measured by stopped-flow light scattering, was reduced in CAII
      deficient mice compared with wild-type mice. These data are consistent with CAII
      increasing water conductance through AQP1 by a physical interaction between the
      two proteins. 

PMID- 25609089
TI  - Notch and TGF-beta pathways cooperatively regulate receptor protein tyrosine
      phosphatase-kappa (PTPRK) gene expression in human primary keratinocytes.
AB  - Receptor protein tyrosine phosphatase-kappa (PTPRK) specifically and directly
      dephosphorylates epidermal growth factor receptor (EGFR), thereby limiting EGFR
      function in primary human keratinocytes. PTPRK expression is increased by the TGF
      beta/Smad3 pathway and cell-cell contact. Because the Notch receptor pathway is
      responsive to cell-cell contact and regulates keratinocyte growth and
      differentiation, we investigated the interplay between Notch and TGF-beta
      pathways in regulation of PTPRK expression in human keratinocytes. Suppression of
      Notch signaling by gamma-secretase inhibitors substantially reduced cell contact
      induction of PTPRK gene expression. In sparse keratinocyte cultures, addition of
      soluble Notch-activating ligand jagged one peptide (Jag1) induced PTPRK. Of
      interest, cell contact-induced expression of TGF-beta1 and TGF-beta receptor
      inhibitor SB431542 inhibited contact-induced expression of PTPRK. Furthermore,
      inhibition of Notch signaling, via knockdown of Notch1 or by gamma-secretase
      inhibitors, significantly reduced TGF-beta-induced PTPRK gene expression,
      indicating that Notch and TGF-beta pathways function together to regulate PTPRK.
      Of importance, the combination of Jag1 plus TGF-beta results in greater PTPRK
      expression and lower EGFR tyrosine phosphorylation than either ligand alone.
      These data indicate that Notch and TGF-beta act in concert to stimulate induction
      of PTPRK, which suppresses EGFR activation in human keratinocytes. 

PMID- 25609090
TI  - Actin-binding protein G (AbpG) participates in modulating the actin cytoskeleton
      and cell migration in Dictyostelium discoideum.
AB  - Cell migration is involved in various physiological and pathogenic events, and
      the complex underlying molecular mechanisms have not been fully elucidated. The
      simple eukaryote Dictyostelium discoideum displays chemotactic locomotion in
      stages of its life cycle. By characterizing a Dictyostelium mutant defective in
      chemotactic responses, we identified a novel actin-binding protein serving to
      modulate cell migration and named it actin-binding protein G (AbpG); this 971
      amino acid (aa) protein contains an N-terminal type 2 calponin homology (CH2)
      domain followed by two large coiled-coil regions. In chemoattractant gradients,
      abpG(-) cells display normal directional persistence but migrate significantly
      more slowly than wild-type cells; expressing Flag-AbpG in mutant cells eliminates
      the motility defect. AbpG is enriched in cortical/lamellipodial regions and
      colocalizes well with F-actin; aa 401-600 and aa 501-550 fragments of AbpG show
      the same distribution as full-length AbpG. The aa 501-550 region of AbpG, which
      is essential for AbpG to localize to lamellipodia and to rescue the phenotype of
      abpG(-) cells, is sufficient for binding to F-actin and represents a novel actin
      binding protein domain. Compared with wild-type cells, abpG(-) cells have
      significantly higher F-actin levels. Collectively our results suggest that AbpG
      may participate in modulating actin dynamics to optimize cell locomotion. 

PMID- 25609091
TI  - STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs.
AB  - STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the
      endoplasmic reticulum (ER) and regulate store-operated Ca(2+) entry (SOCE). The
      function of STIMs in the brain is only beginning to be explored, and the
      relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a
      central organizer of excitatory synapses. STIM2, but not its paralogue STIM1,
      influences the formation of dendritic spines and shapes basal synaptic
      transmission in excitatory neurons. We further demonstrate that STIM2 is
      essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR)
      subunit GluA1. cAMP triggers rapid migration of STIM2 to ER-plasma membrane (PM)
      contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and
      promotes localization of STIM2 in dendritic spines. Both biochemical and imaging
      data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the
      AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in
      regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery
      of GluA1 through combined effects on exocytosis and endocytosis. Collectively our
      results point to a unique mechanism of synaptic plasticity driven by dynamic
      assembly of a STIM2 signaling complex at ER-PM contact sites. 

PMID- 25609092
TI  - Hyphal growth in Candida albicans does not require induction of hyphal-specific
      gene expression.
AB  - Various stimuli, including N-acetylglucosamine (GlcNAc), induce the fungal
      pathogen Candida albicans to switch from budding to hyphal growth. Previous
      studies suggested that hyphal morphogenesis is stimulated by transcriptional
      induction of a set of genes that includes known virulence factors. To better
      understand hyphal development, we examined the role of GlcNAc metabolism using a
      triple mutant lacking the genes required to metabolize exogenous GlcNAc
      (hxk1Delta nag1Delta dac1Delta). Surprisingly, at low ambient pH (~pH 4), GlcNAc
      stimulated this mutant to form hyphae without obvious induction of hyphal genes.
      This indicates that GlcNAc can stimulate a separate signal to induce hyphae that
      is independent of transcriptional responses. Of interest, GlcNAc could induce the
      triple mutant to express hyphal genes when the medium was buffered to a higher pH
      (>pH 5), which normally occurs after GlcNAc catabolism. Catabolism of GlcNAc
      raises the ambient pH rather than acidifying it, as occurs after dextrose
      catabolism. This synergy between alkalinization and GlcNAc to induce hyphal genes
      involves the Rim101 pH-sensing pathway; GlcNAc induced rim101Delta and dfg16Delta
      mutants to form hyphae, but hyphal gene expression was partially defective. These
      results demonstrate that hyphal morphogenesis and gene expression can be
      regulated independently, which likely contributes to pathogenesis at different
      host sites. 

PMID- 25609093
TI  - Rab5-family guanine nucleotide exchange factors bind retromer and promote its
      recruitment to endosomes.
AB  - The retromer complex facilitates the sorting of integral membrane proteins from
      the endosome to the late Golgi. In mammalian cells, the efficient recruitment of
      retromer to endosomes requires the lipid phosphatidylinositol 3-phosphate (PI3P)
      as well as Rab5 and Rab7 GTPases. However, in yeast, the role of Rabs in
      recruiting retromer to endosomes is less clear. We identified novel physical
      interactions between retromer and the Saccharomyces cerevisiae VPS9-domain Rab5
      family guanine nucleotide exchange factors (GEFs) Muk1 and Vps9. Furthermore, we
      identified a new yeast VPS9 domain-containing protein, VARP-like 1 (Vrl1), which
      is related to the human VARP protein. All three VPS9 domain-containing proteins
      show localization to endosomes, and the presence of any one of them is necessary
      for the endosomal recruitment of retromer. We find that expression of an active
      VPS9-domain protein is required for correct localization of the
      phosphatidylinositol 3-kinase Vps34 and the production of endosomal PI3P. These
      results suggest that VPS9 GEFs promote retromer recruitment by establishing PI3P
      enriched domains at the endosomal membrane. The interaction of retromer with
      distinct VPS9 GEFs could thus link GEF-dependent regulatory inputs to the
      temporal or spatial coordination of retromer assembly or function. 

PMID- 25609095
TI  - The distribution of apolipoprotein E genotype over the adult lifespan and in
      relation to country of birth.

PMID- 25609094
TI  - Cyclin C mediates stress-induced mitochondrial fission and apoptosis.
AB  - Mitochondria are dynamic organelles that undergo constant fission and fusion
      cycles. In response to cellular damage, this balance is shifted dramatically
      toward fission. Cyclin C-Cdk8 kinase regulates transcription of diverse gene
      sets. Using knockout mouse embryonic fibroblasts (MEFs), we demonstrate that
      cyclin C directs the extensive mitochondrial scission induced by the anticancer
      drug cisplatin or oxidative stress. This activity is independent of
      transcriptional regulation, as Cdk8 is not required for this activity.
      Furthermore, adding purified cyclin C to unstressed permeabilized MEF cultures
      induced complete mitochondrial fragmentation that was dependent on the fission
      factors Drp1 and Mff. To regulate fission, a portion of cyclin C translocates
      from the nucleus to the cytoplasm, where it associates with Drp1 and is required
      for its enhanced mitochondrial activity in oxidatively stressed cells. In
      addition, although HeLa cells regulate cyclin C in a manner similar to MEF cells,
      U2OS osteosarcoma cultures display constitutively cytoplasmic cyclin C and
      semifragmented mitochondria. Finally, cyclin C, but not Cdk8, is required for
      loss of mitochondrial outer membrane permeability and apoptosis in cells treated
      with cisplatin. In conclusion, this study suggests that cyclin C connects stress
      induced mitochondrial hyperfission and programmed cell death in mammalian cells. 

PMID- 25609096
TI  - Selecting on treatment: a pervasive form of bias in instrumental variable
      analyses.
AB  - Instrumental variable (IV) methods are increasingly being used in comparative
      effectiveness research. Studies using these methods often compare 2 particular
      treatments, and the researchers perform their IV analyses conditional on
      patients' receiving this subset of treatments (while ignoring the third option of
      "neither treatment"). The ensuing selection bias that occurs due to this
      restriction has gone relatively unnoticed in interpretations and discussions of
      these studies' results. In this paper we describe the structure of this selection
      bias with examples drawn from commonly proposed instruments such as calendar time
      and preference, illustrate the bias with causal diagrams, and estimate the
      magnitude and direction of possible bias using simulations. A noncausal
      association between the proposed instrument and the outcome can occur in analyses
      restricted to patients receiving a subset of the possible treatments. This
      results in bias in the numerator for the standard IV estimator; the bias is
      amplified in the treatment effect estimate. The direction and magnitude of the
      bias in the treatment effect estimate are functions of the distribution of and
      relationships between the proposed instrument, treatment values, unmeasured
      confounders, and outcome. IV methods used to compare a subset of treatment
      options are prone to substantial biases, even when the proposed instrument
      appears relatively strong. 

PMID- 25609097
TI  - Racial-Ethnic Differences in Parental Body Image Perceptions of Preschoolers:
      Implications for Engaging Minority Parents in Weight-Related Discussions.

PMID- 25609098
TI  - Lifestyle Behaviors of Parents of Children in Pediatric Weight Management: Are
      They Meeting Recommendations?
AB  - OBJECTIVE: Our objective was to examine the lifestyle behaviors of parents of
      children in pediatric weight management. METHODS: Parents were recruited upon
      presentation of their children (body mass index [BMI] >=85th percentile) to a
      pediatric weight management clinic. Parents' demographic, anthropometric, and
      lifestyle habit data were collected by self-report. Parents were grouped into
      weight status categories based on their BMIs; lifestyle data were compared across
      BMI categories and to national recommendations. RESULTS: Parents (n = 266; 84%
      women; BMI, mean +/- SD, 31.8 +/- 7.2 kg/m(2)) were predominantly
      overweight/obese (82%), and most did not meet dietary recommendations (71%).
      Healthy-weight parents reported more daily steps versus parents who were
      overweight/obese (all P < .05). Most parents (~60%) met guidelines for physical
      activity, sedentary activity, and sleep. CONCLUSION: The high prevalence of
      overweight and obesity combined with suboptimal dietary behaviors highlight the
      need to address both children's and parents' lifestyle habits in pediatric weight
      management.

PMID- 25609099
TI  - Physician Intervention for Improving Tobacco Control Among Parents Who Use
      Tobacco.
AB  - Research has demonstrated that parents who smoke are often inadvertent sources of
      their children's first cigarettes. Teaching parents to restrict their tobacco may
      give pediatricians another method for helping parents who are not ready to quit
      smoking. This purpose of this study was to determine the feasibility of a program
      training pediatricians to discuss tobacco control with smoking parents and to
      examine changes in parents' tobacco control after the physician intervention. One
      month after the intervention by pediatricians, parents reported significantly
      improved tobacco control. They were more likely to count their packs and
      cigarettes and to keep their tobacco products at work and on their person.
      Parents reported restricting household control of adult smoking, and children
      were exposed to significantly less secondhand smoke. These results showed that it
      is possible to integrate advice about tobacco control into a busy pediatric
      practice and to improve parents' restrictions of their tobacco products. 

PMID- 25609103
TI  - Synchronization of action potentials during low-magnesium-induced bursting.
AB  - The relationship between mono- and polysynaptic strength and action potential
      synchronization was explored using a reduced external Mg(2+) model. Single and
      dual whole cell patch-clamp recordings were performed in hippocampal cultures in
      three concentrations of external Mg(2+). In decreased Mg(2+) medium, the
      individual cells transitioned to spontaneous bursting behavior. In lowered Mg(2+)
      media the larger excitatory synaptic events were observed more frequently and
      fewer transmission failures occurred, suggesting strengthened synaptic
      transmission. The event synchronization was calculated for the neural action
      potentials of the cell pairs, and it increased in media where Mg(2+)
      concentration was lowered. Analysis of surrogate data where bursting was present,
      but no direct or indirect connections existed between the neurons, showed minimal
      action potential synchronization. This suggests the synchronization of action
      potentials is a product of the strengthening synaptic connections within neuronal
      networks. 

PMID- 25609104
TI  - Temporal integration at consecutive processing stages in the auditory pathway of
      the grasshopper.
AB  - Temporal integration in the auditory system of locusts was quantified by
      presenting single clicks and click pairs while performing intracellular
      recordings. Auditory neurons were studied at three processing stages, which form
      a feed-forward network in the metathoracic ganglion. Receptor neurons and most
      first-order interneurons ("local neurons") encode the signal envelope, while
      second-order interneurons ("ascending neurons") tend to extract more complex,
      behaviorally relevant sound features. In different neuron types of the auditory
      pathway we found three response types: no significant temporal integration (some
      ascending neurons), leaky energy integration (receptor neurons and some local
      neurons), and facilitatory processes (some local and ascending neurons). The
      receptor neurons integrated input over very short time windows (<2 ms). Temporal
      integration on longer time scales was found at subsequent processing stages,
      indicative of within-neuron computations and network activity. These different
      strategies, realized at separate processing stages and in parallel neuronal
      pathways within one processing stage, could enable the grasshopper's auditory
      system to evaluate longer time windows and thus to implement temporal filters,
      while at the same time maintaining a high temporal resolution. 

PMID- 25609105
TI  - Timing of continuous motor imagery: the two-thirds power law originates in
      trajectory planning.
AB  - The two-thirds power law, v = gammakappa(-1/3), expresses a robust local
      relationship between the geometrical and temporal aspects of human movement,
      represented by curvature kappa and speed v, with a piecewise constant gamma. This
      law is equivalent to moving at a constant equi-affine speed and thus constitutes
      an important example of motor invariance. Whether this kinematic regularity
      reflects central planning or peripheral biomechanical effects has been strongly
      debated. Motor imagery, i.e., forming mental images of a motor action, allows
      unique access to the temporal structure of motor planning. Earlier studies have
      shown that imagined discrete movements obey Fitts's law and their durations are
      well correlated with those of actual movements. Hence, it is natural to examine
      whether the temporal properties of continuous imagined movements comply with the
      two-thirds power law. A novel experimental paradigm for recording sparse imagery
      data from a continuous cyclic tracing task was developed. Using the likelihood
      ratio test, we concluded that for most subjects the distributions of the marked
      positions describing the imagined trajectory were significantly better explained
      by the two-thirds power law than by a constant Euclidean speed or by two other
      power law models. With nonlinear regression, the beta parameter values in a
      generalized power law, v = gammakappa(-beta), were inferred from the marked
      position records. This resulted in highly variable yet mostly positive beta
      values. Our results imply that imagined trajectories do follow the two-thirds
      power law. Our findings therefore support the conclusion that the coupling
      between velocity and curvature originates in centrally represented motion
      planning. 

PMID- 25609106
TI  - Asymmetric generalization in adaptation to target displacement errors in humans
      and in a neural network model.
AB  - Different error signals can induce sensorimotor adaptation during visually guided
      reaching, possibly evoking different neural adaptation mechanisms. Here we
      investigate reach adaptation induced by visual target errors without perturbing
      the actual or sensed hand position. We analyzed the spatial generalization of
      adaptation to target error to compare it with other known generalization patterns
      and simulated our results with a neural network model trained to minimize target
      error independent of prediction errors. Subjects reached to different peripheral
      visual targets and had to adapt to a sudden fixed-amplitude displacement ("jump")
      consistently occurring for only one of the reach targets. Subjects simultaneously
      had to perform contralateral unperturbed saccades, which rendered the reach
      target jump unnoticeable. As a result, subjects adapted by gradually decreasing
      reach errors and showed negative aftereffects for the perturbed reach target.
      Reach errors generalized to unperturbed targets according to a translational
      rather than rotational generalization pattern, but locally, not globally. More
      importantly, reach errors generalized asymmetrically with a skewed generalization
      function in the direction of the target jump. Our neural network model reproduced
      the skewed generalization after adaptation to target jump without having been
      explicitly trained to produce a specific generalization pattern. Our combined
      psychophysical and simulation results suggest that target jump adaptation in
      reaching can be explained by gradual updating of spatial motor goal
      representations in sensorimotor association networks, independent of learning
      induced by a prediction-error about the hand position. The simulations make
      testable predictions about the underlying changes in the tuning of sensorimotor
      neurons during target jump adaptation. 

PMID- 25609107
TI  - Amplitude and dynamics of polarization-plane signaling in the central complex of
      the locust brain.
AB  - The polarization pattern of skylight provides a compass cue that various insect
      species use for allocentric orientation. In the desert locust, Schistocerca
      gregaria, a network of neurons tuned to the electric field vector (E-vector)
      angle of polarized light is present in the central complex of the brain.
      Preferred E-vector angles vary along slices of neuropils in a compasslike fashion
      (polarotopy). We studied how the activity in this polarotopic population is
      modulated in ways suited to control compass-guided locomotion. To this end, we
      analyzed tuning profiles using measures of correlation between spike rate and E
      vector angle and, furthermore, tested for adaptation to stationary angles. The
      results suggest that the polarotopy is stabilized by antagonistic integration
      across neurons with opponent tuning. Downstream to the input stage of the
      network, responses to stationary E-vector angles adapted quickly, which may
      correlate with a tendency to steer a steady course previously observed in
      tethered flying locusts. By contrast, rotating E-vectors corresponding to changes
      in heading direction under a natural sky elicited nonadapting responses. However,
      response amplitudes were particularly variable at the output stage, covarying
      with the level of ongoing activity. Moreover, the responses to rotating E-vector
      angles depended on the direction of rotation in an anticipatory manner. Our
      observations support a view of the central complex as a substrate of higher-stage
      processing that could assign contextual meaning to sensory input for motor
      control in goal-driven behaviors. Parallels to higher-stage processing of sensory
      information in vertebrates are discussed. 

PMID- 25609108
TI  - Dynamics of 3D view invariance in monkey inferotemporal cortex.
AB  - Rotations in depth are challenging for object vision because features can appear,
      disappear, be stretched or compressed. Yet we easily recognize objects across
      views. Are the underlying representations view invariant or dependent? This
      question has been intensely debated in human vision, but the neuronal
      representations remain poorly understood. Here, we show that for naturalistic
      objects, neurons in the monkey inferotemporal (IT) cortex undergo a dynamic
      transition in time, whereby they are initially sensitive to viewpoint and later
      encode view-invariant object identity. This transition depended on two aspects of
      object structure: it was strongest when objects foreshortened strongly across
      views and were similar to each other. View invariance in IT neurons was present
      even when objects were reduced to silhouettes, suggesting that it can arise
      through similarity between external contours of objects across views. Our results
      elucidate the viewpoint debate by showing that view invariance arises dynamically
      in IT neurons out of a representation that is initially view dependent. 

PMID- 25609109
TI  - Bursting by taste-responsive cells in the rodent brain stem.
AB  - Neurons that fire in bursts have been well-characterized in vision and other
      neural systems, but not in taste systems. We therefore examined whether brain
      stem gustatory neurons fire in bursts during spontaneous activity and, if so,
      whether such cells differ from nonbursting cells in other characteristics. We
      looked at neurons in the nucleus of the solitary tract (NST) of C57BL/6ByJ (B6)
      and 129P3/J (129) mice, and in the NST and parabrachial nucleus (PBN) of Sprague
      Dawley rats. Many NST cells fired frequently with short intervals characteristic
      of bursting, and such neurons differed from others in their responsiveness to
      taste compounds. In B6 mice and rats, there was a significant positive
      correlation between the prevalence of short-interval firing and the net spikes
      evoked by application of NaCl. In contrast, in 129 mice the prevalence of short
      intervals was positively correlated with the size of sucrose responses. We also
      compared breadth-of-tuning measures based on counting either all spikes or only
      those following short intervals, and we found narrower tuning for the latter in
      the NST of B6 mice and rats. There was little evidence of spontaneous bursting in
      the rat PBN, and firing patterns in this nucleus were not related to the size of
      taste-evoked responses. We suggest that bursting may be a strategy employed by
      the NST to amplify the postsynaptic impact of particular taste stimuli, depending
      on an animal's needs. Another function may be to sharpen breadth-of-tuning and
      thus enhance the contrast between stimuli of different taste qualities. 

PMID- 25609110
TI  - Locomotor training improves reciprocal and nonreciprocal inhibitory control of
      soleus motoneurons in human spinal cord injury.
AB  - Pathologic reorganization of spinal networks and activity-dependent plasticity
      are common neuronal adaptations after spinal cord injury (SCI) in humans. In this
      work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after
      locomotor training in 16 people with chronic SCI. The soleus H-reflex depression
      following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve
      stimulation at short conditioning-test (C-T) intervals was assessed before and
      after training in the seated position and during stepping. The conditioned H
      reflexes were normalized to the unconditioned H reflex recorded during seated.
      During stepping, both H reflexes were normalized to the maximal M wave evoked at
      each bin of the step cycle. In the seated position, locomotor training replaced
      reciprocal facilitation with reciprocal inhibition in all subjects, and Ib
      facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During
      stepping, reciprocal inhibition was decreased at early stance and increased at
      midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was
      decreased at midstance and midswing phases in AIS D after training. Ib inhibition
      was decreased at early swing and increased at late swing in AIS C and was
      decreased at early stance phase in AIS D after training. The results of this
      study support that locomotor training alters postsynaptic actions of Ia and Ib
      inhibitory interneurons on soleus motoneurons at rest and during stepping and
      that such changes occur in cases with limited or absent supraspinal inputs. 

PMID- 25609111
TI  - Attentional trade-offs maintain the tracking of moving objects across saccades.
AB  - In many situations like playing sports or driving a car, we keep track of moving
      objects, despite the frequent eye movements that drastically interrupt their
      retinal motion trajectory. Here we report evidence that transsaccadic tracking
      relies on trade-offs of attentional resources from a tracked object's motion path
      to its remapped location. While participants covertly tracked a moving object, we
      presented pulses of coherent motion at different locations to probe the
      allocation of spatial attention along the object's entire motion path. Changes in
      the sensitivity for these pulses showed that during fixation attention shifted
      smoothly in anticipation of the tracked object's displacement. However, just
      before a saccade, attentional resources were withdrawn from the object's current
      motion path and reflexively drawn to the retinal location the object would have
      after saccade. This finding demonstrates the predictive choice the visual system
      makes to maintain the tracking of moving objects across saccades. 

PMID- 25609112
TI  - Novel method to assess axonal excitability using channelrhodopsin-based
      photoactivation.
AB  - Measuring the excitability of individual axons is complicated by the prohibitive
      difficulty in obtaining intracellular recordings. Here, we present an innovative
      methodology that enables local excitability to be measured anywhere in a
      channelrhodopsin (ChR2)-expressing neuron. The approach hinges on activating ChR2
      in a spatially and temporally precise manner while recording the resulting spike
      train from a remote site. We validated this approach in primary afferent neurons
      (PANs). Initial encoding of somatosensory stimuli relies on transduction of the
      physical stimulus into a receptor potential and transformation of the receptor
      potential into a spike train; the transformation process depends on the
      excitability of the most distal PAN endings but, as explained above, is
      extraordinarily difficult to study in situ using traditional methods. Using ChR2
      based photoactivation, we show 1) that excitability differs between the distal
      endings and more proximal portions of PAN axons, 2) that the transformation
      process differs between PANs, and 3) that the transformation process is directly
      affected by inflammation. Beyond presenting an innovative method by which to
      study axonal excitability, this study has validated its utility in helping to
      decipher the earliest stages of somatosensory encoding. 

PMID- 25609113
TI  - The effect of convection on infrared detection by antennal warm cells in the
      bloodsucking bug Rhodnius prolixus.
AB  - Previous work revealed that bloodsucking bugs can discriminate between
      oscillating changes in infrared (IR) radiation and air temperature (T) using two
      types of warm cells located in peg-in-pit sensilla and tapered hairs (Zopf LM,
      Lazzari CR, Tichy H. J Neurophysiol 111: 1341-1349, 2014). These two stimuli are
      encoded and discriminated by the response quotient of the two warm cell types. IR
      radiation stimulates the warm cell in the peg-in-pit sensillum more strongly than
      that in the tapered hair. T stimuli evoke the reverse responses; they stimulate
      the latter more strongly than the former. In nature, IR and T cues are always
      present with certain radiation intensities and air temperatures, here referred to
      as background IR radiation and background T. In this article, we found that the
      response quotient permits the discrimination of IR and T oscillations even in the
      presence of different backgrounds. We show that the two warm cells respond well
      to IR oscillations if the background T operates by natural convection but poorly
      at forced convection, even if the background T is higher than at natural
      convection. Background IR radiation strongly affects the responses to T
      oscillations: the discharge rates of both warm cells are higher the higher the
      power of the IR background. We compared the warm cell responses with the T
      measured inside small model objects shaped like a cylinder, a cone, or a disc.
      The experiments indicate that passive thermal effects of the sense organs rather
      than intrinsic properties of the sensory cells are responsible for the observed
      results. 

PMID- 25609114
TI  - New agents for thromboprotection. A role for factor XII and XIIa inhibition.
AB  - Blood coagulation is essential for hemostasis, however excessive coagulation can
      lead to thrombosis. Factor XII starts the intrinsic coagulation pathway and
      contact-induced factor XII activation provides the mechanistic basis for the
      diagnostic aPTT clotting assay. Despite its function for fibrin formation in test
      tubes, patients and animals lacking factor XII have a completely normal
      hemostasis. The lack of a bleeding tendency observed in factor XII deficiency
      states is in sharp contrast to deficiencies of other components of the
      coagulation cascade and factor XII has been considered to have no function for
      coagulation in vivo. Recently, experimental animal models showed that factor XII
      is activated by an inorganic polymer, polyphosphate, which is released from
      procoagulant platelets and that polyphosphate-driven factor XII activation has an
      essential role in pathologic thrombus formation. Cumulatively, the data suggest
      to target polyphosphate, factor XII, or its activated form factor XIIa for
      anticoagulation. As the factor XII pathway specifically contributes to thrombosis
      but not to hemostasis, interference with this pathway provides a unique
      opportunity for safe anticoagulation that is not associated with excess bleeding.
      The review summarizes current knowledge on factor XII functions, activators and
      inhibitors. 

PMID- 25609115
TI  - Long-term comparison of boomerang-shaped jejunal interposition and Billroth-I
      reconstruction after distal gastrectomy.
AB  - BACKGROUND: Billroth-I (BI) is a simple, physiological method of reconstruction
      following distal gastrectomy. In actuality, postoperative QOL is by no means
      favorable due to the high incidence of post-gastrectomy syndrome. The aim of this
      study is to assess the safety and efficacy of boomerang-shaped jejunal
      interposition (BJI) after distal gastrectomy. METHODS: Sixty-six patients with
      early gastric cancer underwent the BI procedure (n = 33) or BJI (n = 33) after
      distal gastrectomy, following which they were compared for 5 years. Tumor
      characteristics, operative details, postoperative complications and complaints,
      number of meals, and body weight were analyzed. Patients were followed up by
      endoscopy every 12 months. RESULTS: There were no significant differences in the
      incidence of postoperative complications. The incidence of heartburn (30 vs. 0 %,
      P = 0.0009) and oral bitterness (33 vs. 6 %, P = 0.0112) were significantly lower
      in the BJI cases. Endoscopic findings revealed significantly lower incidences of
      reflux esophagitis (24 vs. 0 %, P = 0.0051) and remnant gastritis (70 vs. 3 %, P
      < 0.0001) in the BJI group. The incidence of food stasis was low in both groups
      (12 vs. 15 %). In the BJI group, 30 patients (90 %) were eating 3 meals/day
      within 12 months, whereas in the BI group, 16 patients (48 %) were still eating 5
      meals/day at 12 months or later. CONCLUSIONS: BJI is as safe as BI, but is better
      in terms of improvement in bile reflux and food intake without stasis. This
      procedure, therefore, appears to be a useful method for reconstruction after
      distal gastrectomy.

PMID- 25609116
TI  - Role of gadoxetic acid-enhanced magnetic resonance imaging in the preoperative
      evaluation of small hepatic lesions in patients with colorectal cancer.
AB  - BACKGROUND: The initial abdominal computed tomography (CT) scans of patients with
      colorectal cancer (CRC) sometimes reveal equivocal hepatic lesions. In this
      study, we evaluated the outcomes of equivocal hepatic lesions found by abdominal
      CT and the diagnostic accuracy of subsequent liver magnetic resonance imaging
      (MRI). METHODS: We evaluated data of patients who underwent CRC resection between
      January 1, 2009 and December 31, 2009. Equivocal hepatic lesions of <1 cm in size
      on preoperative staging CT scans were included in this study. Gadoxetic acid
      enhanced liver MRI was subsequently performed in all patients. Hepatic lesions
      that grew during the follow-up period (>= 3 years) were considered potential
      metastases. RESULTS: Overall, 121 equivocal hepatic lesions were detected on
      preoperative staging CT in 65 out of 494 patients (13.2 %) who underwent
      colorectal surgery. Based on subsequent MRI, 11 lesions were classified as
      definitive metastatic lesions and 100 were classified as definitive benign
      lesions, including simple cysts or hemangiomas. Findings in the other 10 lesions
      were still inconclusive even after examining CT and MRI. Of the 11 lesions that
      were classified as metastatic by MRI and were resected, 10 were pathologically
      confirmed as metastases and one lesion was a pathologically benign nodule. All
      100 benign lesions were stable on follow-up imaging and were classified as
      benign. Of the 10 equivocal lesions, 6 increased in size during the follow up,
      suggesting they were early metastases, while 4 were stable. The sensitivity and
      specificity for detecting liver metastases by gadoxetic acid-enhanced MRI of
      small equivocal hepatic lesions found by CT were 100 % (16/16) and 95.2 %
      (100/105), respectively, if MRI was equivocal or indicated definite metastasis.
      The negative predictive value was 100 % (100/100). CONCLUSION: Gadoxetic acid
      enhanced MRI is a useful diagnostic tool for assessing equivocal hepatic lesions
      on preoperative CT of CRC patients that allows increased diagnostic accuracy and
      detection of additional colorectal liver metastasis lesions.

PMID- 25609117
TI  - Achalasia and epiphrenic diverticulum.
AB  - Esophageal epiphrenic diverticulum (EED) is a pseudodiverticulum of pulsion type
      located in the distal 10 cm of the esophagus and frequently associated to
      achalasia. The symptoms and the pathophysiology of achalasia and EED may overlap,
      leading to the speculation that achalasia may be responsible for the symptoms.
      Similarly to patients with achalasia without EED, a careful preoperative
      evaluation is essential in patients with EED. Endoscopy and an esophagram are
      mandatory in the workup of these patients, while esophageal manometry confirms
      the associated motility disorder. Treatment is indicated in all patients fit for
      an operation except those who are asymptomatic with a small EED and no prior
      history of aspiration. Laparoscopic Heller's myotomy and partial fundoplication
      is the most adequate therapy. Diverticulectomy must be added to the procedure in
      large diverticula. Experience with endoscopic therapy is very limited.

PMID- 25609118
TI  - Achalasia and epiphrenic diverticulum.
AB  - Epiphrenic diverticula are a rare disease almost always associated with an
      underlying motility disorder of the esophagus, such as achalasia. Treatment of
      any underlying motility disorder must be included in the management of epiphrenic
      diverticula to prevent postoperative complications and recurrences. Therefore,
      the goal of this paper is to describe the pathophysiology, clinical presentation,
      and proper methods of diagnosis and treatment of patients with epiphrenic
      diverticula. In addition, we aim to provide an overview of the surgical
      management and discuss the indications for surgery and choice of surgical
      approach. In general, surgical intervention is favored for symptomatic patients
      and the optimal surgical approach depends on the size and location of the
      diverticulum. Surgery is not without seemingly high rates of morbidity when a
      myotomy is not performed together with the diverticulectomy, even in those with
      normal manometry. The risk of carcinoma is exceedingly rare and it is usually
      discovered at later stages; therefore, no surveillance programs have been
      established in asymptomatic patients with unresected diverticula. 

PMID- 25609119
TI  - Day Case Thyroid and Parathyroid Surgery: Time to Replicate Same in Developing
      Countries.

PMID- 25609121
TI  - [Diagnosis and treatment of overlap syndrome].

PMID- 25609120
TI  - Schistosoma prevalence in appendicitis.
AB  - BACKGROUND: Schistosomiasis is a waterborne trematode with numerous subtypes
      affecting different areas of the body. Rob Ferreira Hospital is located in an
      endemic area for schistosomiasis in the Lowveld region of South Africa. We set
      out to determine the prevalence of Sch istosoma in appendicitis. METHODS: From
      2009 to 2013, all appendix samples removed in theatre were reviewed. A total of
      304 cases were retrieved. Viable ova, calcified ova, or schistosomal granulomas
      was considered proof of exposure. RESULTS: Thirty-one out of the 304 cases
      revealed evidence of schistosomal exposure, equating to 10.2 %. CONCLUSION: A
      prevalence of more than 10 % is truly significant seeing as how a delayed
      diagnosis can lead to serious complications, or how a misdiagnosis can result in
      unnecessary and often protracted treatment with harmful drugs.

PMID- 25609122
TI  - [Sleep related breathing disorders in international classification of sleep
      disorders-3].

PMID- 25609123
TI  - [Application of non-invasive ventilation in sleep respiratory disorders].

PMID- 25609124
TI  - [A study on rat cardiovascular injury induced by intermittent hypoxia and the
      protective role of adiponectin].
AB  - OBJECTIVE: To observe the effect of chronic intermittent hypoxia (CIH) on rat
      cardiac function and blood pressure, and the protective role of adiponectin (Ad).
      METHODS: A total of 24 male Wistar rats were randomly and equally divided into 3
      groups: normal control group (NC group), chronic intermittent hypoxygen group
      (CIH group) and CIH+Ad group. Normal air breathing for NC group and CHI for CIH
      and CIH+Ad groups were conducted for 28 days. In addition, rats in CIH+Ad group
      were given intravenous adiponectin at a dosage of 20 ug each time, once a week
      for successive 4 weeks. The results of echocardiography, blood pressure, plasma
      adiponectin, endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS)
      were compared among the three groups after 28 days. RESULTS: HE stain showed that
      the myocardial cells of CIH rats were damaged by CIH. Compared with NC group,
      rats in CIH group presented with a greater heart/body weight ratio (0.070 +/-
      0.008 vs. 0.057 +/- 0.009, P < 0.05) and systolic blood pressure [(132 +/- 4) vs.
      (123 +/- 6) mmHg(1 mmHg = 0.133 kPa), P < 0.05] and a lower LVEF [(70.3 +/- 4.1)%
      vs. (84.1 +/- 2.5)%, P < 0.05]. Plasma ET-1 was increased while NO(-)(2)/NO(-)(3)
      and eNOS decreased in CIH group, compared with NC group [(26.2 +/- 6.9) ng/L vs.
      (7.7 +/- 2.7) ng/L, (37 +/- 9) umol/L vs. (65 +/- 10) umol/L, (18 +/- 5)ug/L vs.
      (27 +/- 6) ug/L, respectively; P < 0.05]. The heart/body weight ratio, blood
      pressure and LVEF were improved in CIH+Ad group compared with those in CIH group
      [0.064 +/- 0.009 vs. 0.070 +/- 0.008, (127 +/- 6) mmHg vs. (132 +/- 4) mmHg, P >
      0.05; (79 +/- 7)% vs. (70 +/- 4)%, P < 0.05; respectively]. Plasma ET-1 levels in
      CIH+Ad and CIH groups showed no significant difference, but were significantly
      lower in NC group. However, rats in CIH+Ad group had a higher NO(-)(2)/NO(-)(3)
      level than that in CIH group. Bivariate Correlations showed that NO(-)(2)/NO(
      )(3) and eNOS were negatively correlated with systolic blood pressure while
      heart/body weight ratio, LVEDs, ET-1 and NO(-)(2)/NO(-)(3) were negatively
      correlated with left ventricular ejection fraction. CONCLUSIONS: Through xidative
      stress, ET-1 and NO imbalance and impaired vascular endothelial function, cardiac
      function could be damaged by CIH in rats, while supplement of extrinsic
      adiponectin could improve these damages.

PMID- 25609125
TI  - [Role of hippocampal neuronal intracellular calcium overload in modulating
      cognitive dysfunction and the neuronprotective effect of mematine in a mouse
      model of chronic intermittent hypoxia].
AB  - OBJECTIVE: To investigate the role of hippocampal intracellular calcium overload
      in modulating cognitive dysfunction and the neuronprotective effect of mematine
      in a mouse model of chronic intermittent hypoxia. METHODS: 45 ICR male mice were
      randomly divided into 3 groups: the unhandled control group (UC group, n = 15),
      the chronic intermittent hypoxia (CIH group, n = 15) and the pretreatment
      memantine group (MEM group, n = 15). CIH and MEM mice were subjected to
      intermittent hypoxia while UC mice to room air for 8 h per day during 4 weeks.
      Mice in the MEM group were pretreated with memantine (5 mg/kg) by intraperitoneal
      injection before the cycle started, and those in the UC group and the CIH group
      were treated with same volume of physiological saline. Neurobehavioral
      assessments were performed by Open filed and Morris water maze, [Ca2+]i in
      hippocampal neurons was evaluate by flow cytometry, and the expression of cleaved
      caspase-3, phospho-ERK1/2 in hippocampus were detected by Western blotting.
      RESULTS: Compared with the UC group, CIH mice displayed markedly more locomotor
      activity (P < 0.05) in Open filed test, longer mean escape latency (P < 0.05),
      less number of times of crossing the platform (P < 0.01) and less percentage of
      time in target quadrant (P < 0.01). Furthermore, exposure to CIH enhanced [Ca2+]i
      (vs. UC mice, 155 +/- 12 vs. 92 +/- 8, P < 0.01), and up-regulated the expression
      of cleaved caspase-3 (P < 0.01), but down-regulated the level of phospho-ERK1/2
      (P < 0.05) in the hippocampus. Pre-treatment with memantine significantly
      decreased hyperlocomotion (P < 0.05), attenuated memory deficit (P < 0.05),
      mitigated [Ca2+]i (vs. CIH mice, 90 +/- 8 vs. 155 +/- 12, P < 0.01), decrease the
      expression of cleaved caspase-3 (P < 0.01), but increased the level of phospho
      ERK1/2(P < 0.05) comparing to the CIH group. CONCLUSION: The neurobehavioral
      impairments induced by CIH are mediated, at least in part, by intracellular
      calcium concentration overload, neuron apoptosis, dephosphorylation of ERK1/2,
      which can be attenuated by memantine. Memantine may have a therapeutic effect in
      the neurocognitive impairment associated with OSAHS.

PMID- 25609126
TI  - [The analysis of diagnosis and treatment of inpatients with pulmonary
      thromboembolism in Beijing].
AB  - OBJECTIVE: To investigate the clinical characteristics of inpatients with
      pulmonary thromboembolism (PTE) and the status of its diagnosis and treatment in
      different hospitals in Beijing. METHOD: The clinical data of the inpatients with
      PTE from 18 hospitals with different medical levels in Beijing were
      retrospectively investigated from July 2011 to June 2012. The demographic
      characteristics, risk factors, clinical manifestations, diagnosis and treatment
      were recorded and analyzed. RESULTS: A total of 206 inpatients with PTE were
      recruited, of whom 53.4% were males, and the mean age was (72 +/- 16) years. In
      terms of the clinical manifestations, 76.2% patients had dyspnea, and 28.6% had
      lower limb edema. The diagnosis in 86% patients was confirmed by CTPA and 14% by
      ventilation perfusion scan. Echocardiography was performed in 74.8% patients,
      screening for deep vein thrombosis. In 81.1% patients, and BNP or NT-proBNP
      measurements in 57.8% patients. CTNI was tested in 47.6% patients. All patients
      received anticoagulant therapy, and 8.25% of the patients received thrombolysis.
      No cases received secondary thrombolysis therapy. 1.5% of the patients received
      inferior vena cava filter implantation. The main adverse events were bleeding
      (4.4%) and liver dysfunction (9.2%). The mortality during hospitalization was
      2.9%. Compared with tertiary hospitals, the time from admission to diagnosis was
      shorter, the proportion of intermediate- and high-risk patients was higher in
      secondary hospitals and fewer patients received lung ventilation perfusion scan.
      CONCLUSION: The status of diagnosis and treatment of inpatient with PTE in
      hospitals of different medical levels in Beijing is relatively satisfactory,
      while more attention should be paid to the risk stratification and the
      identification of etiology.

PMID- 25609127
TI  - [The relationship between pulmonary arterial and small airway inflammation in
      smokers with and without chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the relationship between pulmonary arterial and small
      airway inflammation in smokers with normal lung function and smokers with chronic
      obstructive pulmonary disease (COPD). METHODS: Patients requiring lung resection
      for peripheral lung cancer were divided into group A (nonsmokers with normal lung
      function, n = 10), group B (smokers with normal lung function, n = 13) and group
      C (smokers with stable COPD, n = 10). Normal pulmonary tissue was obtained more
      than 5 cm away from cancer lesion. The pathomorphological changes of the
      pulmonary muscularized arteries (MA) and small airways were observed by HE and
      Victoria blue-Van Gieson's stains.Lymphocytes infiltrated in the MA and small
      airways were observed by immunohistochemical methods. The characteristics and the
      correlations between pulmonary arterial inflammation and small airway
      inflammation were analyzed. RESULTS: The thickness of MA wall in the three groups
      was (119 +/- 11), (139 +/- 25) and (172 +/- 28) um respectively. The total small
      airway pathology score was (49 +/- 10), (101 +/- 34) and (163 +/- 36)
      respectively. The score in group B and C was significantly higher than that in
      group A (P < 0.05), and the thickness of MA wall and total small airway pathology
      score in group C was significantly higher than that in group B (P < 0.05). The
      degree of CD(+)(3) T-lymphocytes and CD(+)(8) T-lymphocytes infiltration in the
      intima, media and adventitia of MA and epithelial layer, lamina propria and
      adventitia of small airway in group B and C was more significant than that in
      group A, especially CD(+)(8) T-lymphocytes infiltration in adventitia of MA and
      small airway (P < 0.05). Expression of CD(+)(4) T-lymphocytes on epithelial
      layer, lamina propria and adventitia of small airway in group C was higher than
      that in group A (P < 0.05), but the CD(+)(4)/CD(+)(8) ratio in the whole layer of
      airway wall declined (P < 0.01). Among three groups, the infiltration of B
      lymphocytes in three layers compared each other had no statistical differences (P
      > 0.05). The infiltration of CD(+)(3)T-lymphocytes and CD(+)(8)T-lymphocytes in
      the whole layer of MA was positively correlated with the total small airway
      pathology score respectively (r = 0.431,0.633, P < 0.05), and the degree of
      CD(+)(3)T-lymphocytes and CD(+)(8)T-lymphocytes infiltration in MA showed
      positive correlation with that in small airway (r = 0.655,0.725, P < 0.01). The
      degree of CD(+)(8)T-lymphocytes infiltration in MA and small airway was
      positively correlated with thickness of MA (r = 0.589,0.556, P < 0.01).
      CONCLUSIONS: Both in smokers with normal lung function and smokers with stable
      COPD, CD(+)(8)T-lymphocytes infiltration in the whole layer of pulmonary arteries
      and small airways is the same kind of inflammation, mainly in the adventitia of
      pulmonary arteries and small airways. They are a part of pulmonary inflammation
      in COPD and promote the development of COPD.

PMID- 25609128
TI  - [A study on the relationship between endoplasmic reticulum aminopeptidase2
      genetic polymorphisms and non-small cell lung cancer in Yunnan Han population].
AB  - OBJECTIVE: To evaluate the association between the genetic polymorphisms of
      endoplasmic reticulum aminopeptidase 2 (ERAP2) and the susceptibility of non
      small cell lung cancer (NSCLC) in Yunnan Han population. METHODS: A total of 223
      patients with NSCLC and 205 healthy controls in Yunnan Han population were
      included in the present study. The SNP of rs2248374 and rs2549782 in ERAP2 gene
      were genotyped using TaqMan fluorescence probe technique, and their haplotypes
      were constructed. Then, the association between the two SNPs with NSCLC was
      assessed. RESULTS: The allele A and allele G frequencies for rs2248374 in NSCLC
      patients and the control groups were 45.5% (203/446), 54.5% (243/446) and 37.8%
      (155/410), 62.2% (255/410), respectively (chi2 = 5.220, P < 0.05). The genotypic
      GG, GT, TT for rs2549782 in NSCLC patients and the control groups were 21.5%
      (48/223), 48.9% (109/223), 29.6% (66/223) and 11.7% (24/205), 49.8% (102/205),
      38.5% (79/205), respectively(chi2 = 8.656, P < 0.05). And the allele G and allele
      T frequencies for rs2549782 in NSCLC patients and the control groups were 46.0%
      (205/446), 54.0% (241/446) and 36.6% (150/410), 63.4% (260/410), respectively
      (chi2 = 7.741, P < 0.05). The frequencies of haplotype rs2248374/rs2549782-AG
      were 44.6% (199/446), 36.1% (148/410) and rs2248374/rs2549782-GT were 53.1%
      (237/446), 61.7% (253/410), which also showed difference between NSCLC patients
      and the control groups (chi2 = 6.567, P < 0.01;chi2 = 6.567, P < 0.01). The
      allele A and allele G frequencies for rs2248374 were 52.9% (72/136), 47.1%
      (64/136) and 42.3% (131/310), 57.7% (179/310) in the Cigarette-smoking group and
      the Non-smoking group, respectively (chi2 = 4.498, P < 0.05), while the allele G
      and allele T frequencies for rs2549782 were 54.4% (74/136), 45.6% (62/136) and
      42.3% (131/310), 57.7% (179/310) in the Cigarette-smoking group and the Non
      smoking group, respectively(chi2 = 5.831, P < 0.05). The genotypic AA,AG,GG for
      rs2248374 were 17.3% (24/139), 56.1% (78/139), 26.6% (37/139) and 27.8% (22/79),
      38.0% (30/79), 34.2% (27/79) in lung squamous cell carcinoma and lung
      adenocarcinoma, respectively (chi2 = 6.999, P < 0.05), while the genotypic GG,
      GT, TT for rs2549782 were 18.7% (26/139), 55.4% (77/139), 25.9% (36/139) and
      27.8% (22/79), 36.7% (29/79), 35.4% (28/79) in lung squamous cell carcinoma and
      lung adenocarcinoma, respectively (chi2 = 7.093, P < 0.05). CONCLUSION: ERAP2
      rs2248374 and rs2549782 had a strong association with NSCLC and the pathological
      pattern. The rs2248374/rs2549782-AG haplotype was associated with increased NSCLC
      risk (OR = 1.435, 95%CI: 1.088-1.893), whereas the rs2248374/rs2549782-GT
      haplotype individuals may have a reduced NSCLC risk (OR = 0.697, 95%CI: 0.528
      0.919).

PMID- 25609129
TI  - [The therapeutic effect of regimens containing isoniazid and rifampicin for
      pulmonary tuberculosis with single isoniazid or rifampicin resistance].
AB  - OBJECTIVE: To study regimens containing isoniazid and rifampicin for the
      treatment of pulmonary tuberculosis with isoniazid or rifampicin resistance.
      METHODS: Eighty patients with isoniazid or rifampicin resistance, and whose
      sputum were still positive at the end of 2-month therapy with isoniazid (H),
      rifampicin (R), pyrazineamide (Z) and ethambutol (E), were retrospectively
      analyzed from Jan.2009 to Dec.2012 in Guangzhou Chest Hospital. According to the
      Mycobacterium drug sensitive test (DST) before the treatment with isoniazid and
      rifampicin, the patients were divided into the sensitive group (either H or R
      sensitive), the multidrug-resistance group (both H and R resistance) and the
      single-resistance group (H or R resistance). There were 80 patients (57 females,
      23 males) whose sputum was still positive at the end of 2 month treatment. Their
      ages ranged from 16-80 (average 45) years. Among them, 29 received the first
      treatment, while 51 received retreatment. There were 37 cases in the sensitive
      group, with 18 first-treatment patients and 19 retreatment patients. There were
      15 cases in the single-resistance group, with 3 first-treatment patients and 12
      retreatment patients. There were 28 cases in the multidrug-resistance group, with
      8 first-treatment patients and 20 retreatment patients. RESULTS: After treatment,
      mycobacterial conversion to MDR-TB occurred in 2 patients in the sensitive group,
      and in 6 patients in the single-resistance group. The rate of conversion to MDR
      TB was higher in the single-resistance group than that in the sensitive group
      (chi2 = 12.849, P = 0.000).Six patients with single H resistance converted to MDR
      TB and 2 patients with single R resistance converted to MDR-TB (P < 0.05, RR =
      18.0). CONCLUSIONS: Single H or R drug-resistance was more common in retreated
      patients with pulmonary tuberculosis.If regimens containing isoniazid and
      rifampicin was used to treat patients with single H or R drug-resistance,
      resistant enlarging effect may appear and lead to MDR-TB. The retreated patients
      should be monitored as soon as possible for detection of Mycobacterium resistance
      to H and R, and regimens for H or R-resistance should be used to prevent
      resistant enlarging effect.

PMID- 25609130
TI  - [Thyroid transcription factor-1 level is associated with epidermal growth factor
      receptor mutation status in patients with advanced lung adenocarcinoma].
AB  - OBJECTIVE: Epidermal growth factor receptor (EGFR) mutation status plays an
      important role in individual treatment of non-small cell lung cancer.However
      clinical tissue samples for mutation detection are not always available in
      advanced NSCLC. Thus an alternative method of EGFR mutation detection is required
      in NSCLC treatment.Recent studies have associated thyroid transcription factor 1
      (TTF-1) with EGFR mutations in lung cancer.In this study, we detected expression
      of TTF-1 and EGFR mutations in 102 patients with advanced NSCLC and investigated
      the possibility of TTF-1 as a potential indicator of EGFR status. METHODS: Serum
      and tissue samples were collected from 102 patients with advanced NSCLC including
      28 cases of EGFR mutation in 19 exon, 23 cases of EGFR mutation in 21 exon and 51
      cases of WT EGFR. Protein levels of TTF-1 in serum were quantified by enzyme
      linked immunosorbent assay (ELISA).Levels of TTF-1 in tissues were detected by
      immunohistochemistry (IHC). SPSS 17 statistical software was used to analyze the
      data. RESULTS: In the serum the expression of TTF-1 in EGFR 19 and 21 exon MT
      groups both was higher than that in the WT group(19MT vs 21MT vs WT: 0.092 vs
      0.083 vs 0.045; F = 27.653, P < 0.01), and the result of the tissues was the same
      (19MT vs 21MT vs WT: 0.682 vs 0.644 vs 0.441; F = 47.665, P < 0.01), but no
      differences between two MT groups were observed (P > 0.05). The ELISA results and
      the IHC results were consistent (r = 0.87, P < 0.01). The expression of TTF-1 in
      serum showed a relationship with smoking history (chi2 = 4.639, P < 0.05), but
      not with sex, age, TNM stage and metastasis (P > 0.05). CONCLUSIONS: These
      results indicated that TTF-1 expression was upregulated in EGFR mutated NSCLC
      compared to EGFR WT NSCLC. The level of TTF-1 maybe used as a potential marker of
      EGFR mutation status.

PMID- 25609131
TI  - [The predictive value of gray scale sonographic features in malignant hilar and
      mediastinal lymph node].
AB  - OBJECTIVE: To explore the sonographic features of malignant hilar and mediastinal
      lymph nodes and the predictive value. METHODS: We performed retrospective
      analysis of 390 lymph nodes under the endobronchial ultrasound-guided
      transbronchial needle aspiration for diagnosis in the bronchoscope center of the
      First Affiliated Hospital of Guangzhou Medical University from November 1st, 2012
      to November 31st, 2013. They were divided into malignant and benign groups, and
      sonographic features of lymph nodes were analyzed, including the length of short
      axis, shape, margin, echogenicity, homogenicity, coagulation necrosis,
      calcification, coalesence and posterior acoustic enhancement. RESULTS: A total of
      390 lymph nodes were evaluated, including 207 malignant and 183 benign lymph
      nodes, respectively. The accuracy based on the length of short axis, shape,
      margin, echogenicity, homogenicity, coagulation necrosis, calcification,
      coalesence and posterior acoustic enhancement to predict the malignancy were
      61.0% (238/390), 75.4% (294/390), 75.6% (295/390), 73.8% (288/390), 65.9%
      (257/390), 68.2% (266/390), 51.8% (202/390), 55.1% (215/390), 67.4% (263/390),
      respectively. Binary multivariable logistic regression analysis revealed that 5
      parameters, including round, distinct margin and heterogeneous, hypoechoic, and
      posterior acoustic enhancement possessed a significant predictive value(P <
      0.05).We found that only 35.3% (73/207) malignant lymph nodes possessed these 5
      ultrasonographic characteristics, and the diagnosis rate was 93.6% (73/78).72.46%
      (150/207) malignant lymph nodes possessed any 4 or more positive sonographic
      features, and the diagnosis rate was 85.2% (150/176).85.0% (176/207) malignant
      lymph nodes had any 3 or more positive sonographic features, and the diagnosis
      rate was 84.6% (176/208). CONCLUSION: The combination of gray scale sonographic
      features has a predictive value in the diagnosis of malignant hilar and
      mediastinal lymph nodes.

PMID- 25609132
TI  - [The relationship between erectile dysfunction caused by chronic intermittent
      hypoxia and oxidative stress].

PMID- 25609133
TI  - [New perspective on Th2 and non-Th2 asthma phenotype].

PMID- 25609134
TI  - [Advances in the management of gastroesophageal reflux-induced chronic cough].

PMID- 25609135
TI  - Nitrosative stress and apoptosis in non-anemic healthy rats induced by
      intravenous iron sucrose similars versus iron sucrose originator.
AB  - Iron can both induce and inhibit nitrosative stress. Intracellular iron levels
      play an important role in nitric oxide (NO(*)) signaling mechanisms. Depending on
      various factors, such as the cell's redox state and transition metal levels,
      NO(*) generation may lead to lipid peroxidation and DNA damage as well as both
      anti- and pro-apoptotic effects. Administration of intravenous iron sucrose
      originator (IS(ORIG)) has been shown not to cause significant tyrosine nitration
      or significantly increased caspase 3 levels in non-anemic rats. In this study,
      the potential of several marketed iron sucrose similars (ISSs) to induce tyrosine
      nitration and caspase 3 expression in non-anemic rats was assessed. Although the
      physico-chemical properties of most of the analyzed ISSs complied with the United
      States Pharmacopeia for iron sucrose injection, all ISSs resulted in higher
      levels of tyrosine nitration and increased the expression of caspase 3 versus
      IS(ORIG). Moreover, significant differences were detected in tissue iron
      distribution between IS(ORIG)- and ISS-treated animals. In general, ISORIG
      resulted in higher levels of ferritin deposits versus ISSs whereas ISSs showed
      higher Prussian blue-stainable iron(III) deposits than IS(ORIG). This result
      suggests that some iron from ISSs bypassed the tightly regulated pathway through
      resident macrophages of the liver, spleen and bone marrow thus, ending up in the
      cellular compartment that favors oxidative and or nitrosative stress as well as
      apoptosis. The results also confirm that polynuclear iron(III)-oxyhydroxide
      carbohydrates, such as iron sucrose, cannot be fully characterized by physico
      chemical methods alone.

PMID- 25609136
TI  - Radiographic location of the femoral footprint of the cranial cruciate ligament
      in dogs.
AB  - OBJECTIVE: To describe the radiographic location of the center of the femoral
      footprint of the cranial cruciate ligament (CrCL) in dogs. MATERIAL AND METHODS:
      Using femora from 49 adult, orthopedically sound dogs (bodyweight>=20 kg), a
      radiopaque marker was placed on the cranial border of the femoral footprint of
      the CrCL. Computed tomography and threedimensional (3D) reconstruction of each
      femur was performed subsequently, followed by manual segmentation of the
      footprint on the 3D models and calculation of its center. Finally, virtual
      digital radiographs in two planes were produced and the location of the
      calculated center of the CrCL was expressed using three different methods (4x4
      box grid method and percentage position for the medio-lateral projection; o'clock
      position for the disto-proximal projection). RESULTS: In the medio-lateral
      radiographs the center of the femoral footprint was consistently located in the
      second rectangle from the top of the most caudal column of the 4x4 grid. The mean
      percentage caudo-cranial and proximo-distal location was 20.2% (+/-2.2) and 33.8%
      (+/-3.7), respectively. In the disto-proximal radiograph, the o'clock position of
      the CrCL center was between 2 and 3 o'clock in 97.6% of cases. CONCLUSION: The
      radiographic location of the center of the femoral footprint can be consistently
      predicted in medio-lateral and disto-proximal stifle radiographs of dogs over 20
      kg. CLINICAL SIGNIFICANCE: The reported data can be used to plan and verify the
      placement of the femoral tunnel opening for intra-articular anatomic CrCL repair.

PMID- 25609137
TI  - Prospective analysis of indications and early complications of emergency
      temporary loop ileostomies for perforation peritonitis.
AB  - BACKGROUND: To determine the indications, nature, and rate of early complications
      of temporary loop ileostomy created in emergency for benign diseases, their
      management, and to find out the associated risk factors. METHODS: A total of 630
      patients undergoing temporary loop ileostomy for benign diseases were studied
      prospectively over a period of 6 years. Stoma-related early complications
      occurring within 6-8 weeks were analyzed. Only emergency cases were included in
      this study. Descriptive statistics were used to summarize the data and
      statistical significance was evaluated by applying the Pearson's chi-square test.
      RESULTS: Typhoid perforation (n=402) was the most commonpathology, followed by
      tuberculosis (n=106); trauma (n=81); and intestinal obstruction with gangrenous
      bowel (n=41). 299 patients had no stoma-related complications. Skin excoriation
      was the most commonstoma-related complication. Age more than 50 years; shock at
      presentation; delay in presentation; delay in surgery; presence of comorbidities;
      and surgery done out of working hours, were associated with increased
      complications. CONCLUSION: Temporary loop ileostomy for perforation peritonitis
      due to benign systemic diseases like typhoid fever and tuberculosis confers a
      very high morbidity.

PMID- 25609138
TI  - Hfe and Hjv exhibit overlapping functions for iron signaling to hepcidin.
AB  - Functional inactivation of HFE or hemojuvelin (HJV) is causatively linked to
      adult or juvenile hereditary hemochromatosis, respectively. Systemic iron
      overload results from inadequate expression of hepcidin, the iron regulatory
      hormone. While HJV regulates hepcidin by amplifying bone morphogenetic protein
      (BMP) signaling, the role of HFE in the hepcidin pathway remains incompletely
      understood. We investigated the pathophysiological implications of combined Hfe
      and Hjv ablation in mice. Isogenic Hfe (-)/(-) and Hjv (-)/(-) mice were crossed
      to generate double Hfe (-)/(-) Hjv (-)/(-) progeny. Wild-type control and mutant
      mice of all genotypes were analyzed for serum, hepatic, and splenic iron content,
      expression of iron metabolism proteins, and expression of hepcidin and Smad
      signaling in the liver, in response to a standard or an iron-enriched diet. As
      expected, Hfe (-)/(-) and Hjv (-)/(-) mice developed relatively mild or severe
      iron overload, respectively, which corresponded to the degree of hepcidin
      inhibition. The double Hfe (-)/(-) Hjv (-)/(-) mice exhibited an
      indistinguishable phenotype to single Hjv (-)/(-) counterparts with regard to
      suppression of hepcidin, serum and hepatic iron overload, splenic iron
      deficiency, tissue iron metabolism, and Smad signaling, under both dietary
      regimens. We conclude that the hemochromatotic phenotype caused by disruption of
      Hjv is not further aggravated by combined Hfe/Hjv deficiency. Our results provide
      genetic evidence that Hfe and Hjv operate in the same pathway for the regulation
      of hepcidin expression and iron metabolism. KEY MESSAGES: Combined disruption of
      Hfe and Hjv phenocopies single Hjv deficiency. Single Hjv(-)/(-) and double Hfe(
      )/(-)Hjv(-)/(-) mice exhibit comparable iron overload. Hfe and Hjv regulate
      hepcidin via the same pathway.

PMID- 25609139
TI  - Mitophagy and heart failure.
AB  - Cardiac mitochondria are responsible for generating energy in the form of ATP
      through oxidative phosphorylation and are crucial for cardiac function.
      Mitochondrial dysfunction is a major contributor to loss of myocytes and
      development of heart failure. Myocytes have quality control mechanisms in place
      to ensure a network of functional mitochondria. Damaged mitochondria are degraded
      by a process called mitochondrial autophagy, or mitophagy, where the organelle is
      engulfed by an autophagosome and subsequently delivered to a lysosome for
      degradation. Evidence suggests that mitophagy is important for cellular
      homeostasis, and reduced mitophagy leads to inadequate removal of dysfunctional
      mitochondria. In this review, we discuss the regulation of mitophagy and the
      emerging evidence of the cardioprotective role of mitophagy. We also address the
      prospect of therapeutically targeting mitophagy to treat patients with
      cardiovascular disease. 

PMID- 25609140
TI  - Circulating vitamin D binding protein, total, free and bioavailable 25
      hydroxyvitamin D and risk of colorectal cancer.
AB  - Epidemiological investigation have suggested that there is a significantly
      inverse association between circulating 25-hydroxyvitamin D (25(OH)D) and the
      risk for developing colorectal cancer (CRC) in humans. However, little is known
      about the role of vitamin D binding protein (VDBP) in colorectal carcinogenesis.
      Blood samples were collected from 212 CRC patients and 212 controls matched with
      age, gender and blood collection time. We used logistic regression to calculate
      the odds ratios and 95% confidence intervals for further estimation of the
      association of the quartiles of VDBP, total, free and bioavailable 25(OH)D with
      CRC risk. The results revealed that there was no significant association between
      circulating VDBP concentrations and CRC in the present study, and that a negative
      association existed between total 25(OH)D and the risk of CRC, which was
      unchanged after adjustment for VDBP. Higher levels of free and bioavailable
      25(OH)D were significantly associated with decreased risk of CRC. After
      stratifying by VDBP, high levels of total, free and bioavailable 25(OH)D were
      associated significantly with decreased CRC risk among participants with
      circulating VDBP below the median. These findings indicate that VDBP is not
      directly associated with the risk of CRC, but it modulates circulating free and
      bioavailable 25(OH)D concentration. 

PMID- 25609141
TI  - Thyrotropin and Alzheimer's Disease Risk in the Elderly: a Systematic Review and
      Meta-Analysis.
AB  - Although several epidemiological studies assessed the relationship between
      thyrotropin and risk of Alzheimer's disease in the elderly, the results were
      inconsistent. A systematic review and meta-analysis of cohort studies was
      conducted to assess the impact of serum thyrotropin levels on Alzheimer's disease
      risk. PubMed, Embase, and Web of Science were searched through September 20, 2014
      to identify cohort studies on the relationship between serum thyrotropin levels
      and risk of Alzheimer's disease in the elderly. Pooled relative risks (RR) and
      95% confidence intervals (95% CI) were calculated to assess the risk of
      Alzheimer's disease according to serum thyrotropin levels. Eight prospective
      cohort studies were included, with a total of 9456 participants and 640 cases of
      Alzheimer's disease. Low thyrotropin level was significantly associated with an
      increased risk of Alzheimer's disease (fixed RR = 1.69, 95% CI 1.31-2.19, P <
      0.001; I(2) = 38.0%). High thyrotropin level was also significantly associated
      with an increased risk of Alzheimer's disease (fixed RR = 1.70, 95% CI 1.18-2.45,
      P = 0.005; I(2) = 42.2%) when compared with normal thyrotropin level. When using
      random effect model, low thyrotropin level was still significantly associated
      with risk of Alzheimer's disease (random RR = 1.65, 95% CI 1.14-2.37, P = 0.007),
      but high thyrotropin level was not (random RR = 1.54, 95% CI 0.88-2.68, P =
      0.129). When investigating thyrotropin levels continuously, an inverse but not
      significant association between serum thyrotropin levels and Alzheimer's disease
      risk was observed (per standard deviation increment of thyrotropin: RR = 0.89,
      95% CI 0.78-1.01, P = 0.06; I(2) = 31.3%). This meta-analysis supports that low
      thyrotropin level is significantly associated with an increased risk of
      Alzheimer's disease in the elderly.

PMID- 25609143
TI  - Structural analysis of herpes simplex virus by optical super-resolution imaging.
AB  - Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among
      humans. Although the structure of HSV-1 has been extensively investigated, the
      precise organization of tegument and envelope proteins remains elusive. Here we
      use super-resolution imaging by direct stochastic optical reconstruction
      microscopy (dSTORM) in combination with a model-based analysis of single-molecule
      localization data, to determine the position of protein layers within virus
      particles. We resolve different protein layers within individual HSV-1 particles
      using multi-colour dSTORM imaging and discriminate envelope-anchored
      glycoproteins from tegument proteins, both in purified virions and in virions
      present in infected cells. Precise characterization of HSV-1 structure was
      achieved by particle averaging of purified viruses and model-based analysis of
      the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and
      envelope protein gD. From this data, we propose a model of the protein
      organization inside the tegument. 

PMID- 25609144
TI  - Metagenomic and metabolomic analysis of the toxic effects of trichloroacetamide
      induced gut microbiome and urine metabolome perturbations in mice.
AB  - Disinfection byproducts (DBPs) in drinking water have been linked to various
      diseases, including colon, colorectal, rectal, and bladder cancer.
      Trichloroacetamide (TCAcAm) is an emerging nitrogenous DBP, and our previous
      study found that TCAcAm could induce some changes associated with host-gut
      microbiota co-metabolism. In this study, we used an integrated approach combining
      metagenomics, based on high-throughput sequencing, and metabolomics, based on
      nuclear magnetic resonance (NMR), to evaluate the toxic effects of TCAcAm
      exposure on the gut microbiome and urine metabolome. High-throughput sequencing
      revealed that the gut microbiome's composition and function were significantly
      altered after TCAcAm exposure for 90 days in Mus musculus mice. In addition,
      metabolomic analysis showed that a number of gut microbiota-related metabolites
      were dramatically perturbed in the urine of the mice. These results may provide
      novel insight into evaluating the health risk of environmental pollutants as well
      as revealing the potential mechanism of TCAcAm's toxic effects. 

PMID- 25609145
TI  - Complex magnetic behaviour of Sr2CoNb1-xTixO6 (0 <= x <= 0.5) as a result of a
      flexible microstructure.
AB  - We report the rich magnetic behaviour of Sr2CoNb1-xTixO6 (0 <= x <= 0.5) oxides
      as a result of their complex microstructure. Although these oxides show an
      average simple-cubic perovskite structure, they present a flexible microstructure
      due to short-range ordering between Co/Ti and Nb cations in the perovskite B
      sites. The microstructure consists of double-cubic perovskite domains grown in a
      simple-cubic perovskite matrix. The size and number of the double-cubic
      perovskite domains decrease as the Ti content increases. As a result of
      aliovalent substitution of Nb(5+) by Ti(4+) in the parent Sr2CoNbO6 mixed-valence
      Co(3+)/Co(4+) oxides are obtained. A spin glass-like state has been observed at
      low temperatures for all the series, with freezing temperatures increasing with
      the Ti-content in the range 22 to 33 K. Furthermore, the x = 0.3 and x = 0.5
      samples show non-interacting superparamagnetic particle-like dynamics associated
      with relatively high amounts of Co(4+), with "blocking temperatures" of 13 and
      ~16 K, respectively. The complex magnetic behaviour of the title oxides seems to
      be connected with the clustering of magnetic Co(3+) and the distribution of
      Co(4+) as a result of the microstructure. 

PMID- 25609142
TI  - A proteomic approach reveals integrin activation state-dependent control of
      microtubule cortical targeting.
AB  - Integrin activation, which is regulated by allosteric changes in receptor
      conformation, enables cellular responses to the chemical, mechanical and
      topological features of the extracellular microenvironment. A global view of how
      activation state converts the molecular composition of the region proximal to
      integrins into functional readouts is, however, lacking. Here, using conformation
      specific monoclonal antibodies, we report the isolation of integrin activation
      state-dependent complexes and their characterization by mass spectrometry.
      Quantitative comparisons, integrating network, clustering, pathway and image
      analyses, define multiple functional protein modules enriched in a conformation
      specific manner. Notably, active integrin complexes are specifically enriched for
      proteins associated with microtubule-based functions. Visualization of
      microtubules on micropatterned surfaces and live cell imaging demonstrate that
      active integrins establish an environment that stabilizes microtubules at the
      cell periphery. These data provide a resource for the interrogation of the global
      molecular connections that link integrin activation to adhesion signalling. 

PMID- 25609146
TI  - Evaluation of a method for induction of praziquantel resistance in Schistosoma
      mansoni.
AB  - CONTEXT: Praziquantel (PZQ) is a highly efficacious anthelmintic against many
      flatworms including schistosomes. PZQ has been in use for more than 25 years, and
      concern is increasing that resistance has emerged in human schistosomes in Egypt
      and other endemic countries. OBJECTIVE: The current study was designed to
      evaluate a recently described method for induction of PZQ resistance in
      Schistosoma mansoni. MATERIALS AND METHODS: Successive subcurative drug
      treatments of Biomphalaria alexandrina snails infected with an Egyptian strain of
      S. mansoni were undertaken. Cercariae shed from snails exposed and unexposed to
      PZQ were used to infect mice. Forty-five days after infection, mice were treated
      with a single oral dose of PZQ in 2% aqueous solution of Cremophor-EL(r). The
      concentration of PZQ was 0, 200, 400, or 800 mg/kg. Thirty-three days after
      treatment, all groups of mice were dissected to collect the S. mansoni worms by
      the perfusion technique. In addition, the oogram pattern was examined to study
      the production, maturity, and death of S. mansoni eggs in the different groups of
      mice. RESULTS: The present study has shown that the sublethal dose for induction
      of PZQ resistance in the intra-molluscan S. mansoni stages was 500 mg/kg. The
      worm count and the percentage of immature eggs in different groups of mice were
      significantly affected by the intra-molluscan exposure to PZQ and the drug
      concentration used to treat infected mice. DISCUSSION AND CONCLUSION: The results
      obtained herein confirm the possibility of using successive drug treatments of
      infected B. alexandrina to induce PZO resistance in S. mansoni.

PMID- 25609148
TI  - Alteration of pentylenetetrazole-induced seizure threshold by chronic
      administration of ginger (Zingiber officinale) extract in male mice.
AB  - CONTEXT: Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in
      traditional Chinese medicine, has antioxidant activity and neuroprotective
      effects. The effects of this plant on clonic seizure have not yet been studied.
      OBJECTIVE: The present study evaluated the anticonvulsant effect of ginger in a
      model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice.
      MATERIALS AND METHODS: The anticonvulsant effect of Z. officinale was
      investigated using i.v. PTZ-induced seizure models in mice. Different doses of
      the hydroethanolic extract of Z. officinale (25, 50, and 100 mg/kg) were
      administered intraperitonal (i.p.), daily for 1 week before induction of PTZ.
      Phenobarbital sodium (30 mg/kg), a reference standard, was also tested for
      comparison. The effect of ginger on to the appearance of three separate seizure
      endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was
      recorded. RESULTS: Hydroethanolic extract of Z. officinale significantly
      increased the onset time of myoclonic seizure at doses of 25-100 mg/kg (55.33 +/-
      1.91 versus 24.47 +/- 1.33 mg/kg, p < 0.001) and significantly prevented
      generalized clonic (74.64 +/- 3.52 versus 47.72 +/- 2.31 mg/kg, p < 0.001) and
      increased the threshold for the forelimb tonic extension (102.6 +/- 5.39 versus
      71.82 +/- 7.82 mg/kg, p < 0.01) seizure induced by PTZ compared with the control
      group. DISCUSSION AND CONCLUSION: Based on the results, the hydroethanolic
      extract of ginger has anticonvulsant effects, possibly through an interaction
      with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative
      stress inhibition.

PMID- 25609147
TI  - The effects of arctigenin on human rheumatoid arthritis fibroblast-like
      synoviocytes.
AB  - CONTEXT: Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an
      important role in the initiation and progression of RA, which are resistant to
      apoptosis and proliferate in an anchorage-independent manner. OBJECTIVE: The
      effects of arctigenin on the proliferation and apoptosis of RAFLSs were explored.
      MATERIALS AND METHODS: Arctigenin (0-160 uM) was used to treat RAFLSs for 48 h.
      Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining. Western
      blot analysis was performed to detect the changes in apoptosis-related genes.
      RESULTS AND DISCUSSION: Arctigenin decreased cell viability by 23, 30, and 38% at
      the dose of 10, 20, and 30 uM, respectively. The half maximal inhibitory
      concentration (IC50) of arctignein on RAFLSs was about 38 uM. Moreover, 9, 15,
      and 21% of RAFLSs are induced apoptosis by 10, 20, and 30 uM of arctigenin. The
      apoptotic response was due to the loss of mitochondrial membrane potential,
      coupled with the release of cytochrome C into cytoplasm, the up-regulation of pro
      apoptotic protein, Bax, and down-regulation of antiapoptotic protein, B cell
      lymphoma 2 (Bcl-2). The activation of mitochondrial pathway in arctigenin-treated
      RAFLSs induced the cleavage of caspase-9, caspase-3, and poly (ADP-ribose)
      polymerase (PARP). Additionally, arctigenin inhibited the nuclear translocation
      of p65, decreased the degradation of inhibitor of kappa B alpha (IkappaBalpha),
      and attenuated the phosphorylation of Akt. CONCLUSION: Our results reveal that
      arctigenin inhibits cell proliferation and induces mitochondrial apoptosis of
      RAFLSs, which is associated with the modulation of NF-kappaB and Akt signaling
      pathways.

PMID- 25609149
TI  - Thunbergia laurifolia extract ameliorates cognitive and emotional deficits in
      olfactorectomized mice.
AB  - CONTEXT: Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant
      used for the detoxification of poison which is likely to be beneficial for the
      treatment of cognitive deficits including Alzheimer's disease. OBJECTIVE: To
      elucidate the effects of Thunbergia laurifolia leaf extract (TLL) on cognitive
      dysfunction and depression-like behavior in olfactory bulbectomized mice (OBX).
      MATERIALS AND METHODS: OBX mice were treated daily with TLL at the dose of 250
      and 500 mg/kg, tacrine, and imipramine, on the day after 10 d of OBX operation.
      The effects of TLL on cognitive and depression-like behavior of the animals were
      analyzed. After completing behavioral experiments, the expression levels of
      cholinergic marker genes encoding ChAT and muscarinic M1 receptor were
      quantitatively analyzed. RESULTS: TLL and tacrine reduced OBX-induced cognitive
      deficits in the object recognition test (ORT) with the time spent for the novel
      object two times longer than that of the familiar object. Moreover, TLL at the
      dose of 500 mg/kg and imipramine ameliorated depression-like behavior in the tail
      suspension test (TST) by reducing the duration of immobility from 25.18% to 3.16%
      and from 25.18% to 6.48%, respectively. TLL at the dose of 250 and 500 mg/kg
      reversed the OBX-induced down-regulation of ChAT mRNA expression in the
      hippocampus from 0.12 to 0.17 and 0.24, respectively, while the down-regulation
      of mRNA expression of muscarinic M1 receptor was also reversed by TLL from 0.23
      to 0.38 and 0.48, respectively. CONCLUSIONS: TLL ameliorates non-spatial short
      term memory deficits in OBX mice, and has the potential to exhibit an
      antidepressant-like action.

PMID- 25609150
TI  - Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA
      levels in fructose-fed rats.
AB  - CONTEXT: Melatonin, a pineal hormone and a potent antioxidant, has important
      roles in metabolic regulation. OBJECTIVE: This study investigated serum
      asymmetric dimethylarginine (ADMA), homocysteine (Hcy), nitric oxide (NO) levels,
      known to be reliable markers of cardiovascular diseases, and determined possible
      protective effects of melatonin in fructose-fed rats. MATERIALS AND METHODS:
      Sprague-Dawley rats were divided into four groups: control, fructose, melatonin,
      and fructose plus melatonin. Metabolic syndrome was induced in rats by 20% (w/v)
      fructose solution in tap water, and melatonin was administered at the dose of 20
      mg/kg bw per day by oral gavage. After 8 weeks, serum lipids, glucose, insulin,
      ADMA, Hcy, and NOx (the stable end products of NO) levels were quantified.
      RESULTS: Fructose administration caused a statistically significant increase in
      systolic blood pressure (SBP), serum insulin, triglycerides, and very low-density
      lipoprotein (VLDL)-cholesterol levels compared with the control group and the
      metabolic syndrome model was successfully demonstrated. In comparison with the
      control group, fructose caused a significant increase in serum ADMA, Hcy, and NOx
      levels. Melatonin counteracted the changes in SBP, serum ADMA, and Hcy levels
      found in rats both alone and administered with fructose. DISCUSSION AND
      CONCLUSION: These results show that high fructose consumption leads to elevated
      SBP, atherogenic lipid profile, increased serum ADMA, and Hcy levels and
      melatonin treatment has beneficial effects on these biochemical parameters in
      rats. Melatonin might be beneficial for the prevention and/or treatment of the
      cardiovascular complications of metabolic syndrome not only by reducing the well
      known risk factors of the disease but also by diminishing blood ADMA and Hcy
      levels.

PMID- 25609151
TI  - Nerium indicum leaf alleviates iron-induced oxidative stress and hepatic injury
      in mice.
AB  - CONTEXT: Nerium indicum Mill. (Apocynaceae) was reported for its efficient in
      vitro antioxidant and iron-chelating properties. OBJECTIVE: This study
      demonstrates the effect of 70% methanol extract of N. indicum leaf (NIME) towards
      in vitro DNA protection and ameliorating iron-overload-induced liver damage in
      mice. MATERIALS AND METHODS: Phytochemical and HPLC analyses were carried out to
      standardize the extract and the effect of Fe(2+)-mediated pUC18 DNA cessation was
      studied. Thirty-six Swiss Albino mice were divided into six groups of blank,
      negative control (iron overload only), and iron-overloaded mice receiving 50,
      100, and 200 mg/kg b.w. doses of NIME and desirox (20 mg/kg b.w.). The
      biochemical markers of hepatic damage, various liver and serum parameters, and
      reductive release of ferritin iron were studied. RESULTS AND DISCUSSION: The
      presence of different phytocomponents was revealed from phytochemical and HPLC
      analyses. A substantial supercoiled DNA protection, with [P]50 of 70.33 +/- 0.32
      ug, was observed. NIME (200 mg/kg b.w.) significantly normalized the levels of
      alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and
      bilirubin by 126.27, 125.25, 188.48, and 45.47%, respectively. NIME (200 mg/kg
      b.w.) was shown to alleviate the reduced levels of superoxide dismutase,
      catalase, glutathione-S-transferase, and non-enzymatic-reduced glutathione, by
      48.95, 35.9, 35.42, and 13.22%, respectively. NIME also lowered raised levels of
      lipid peroxidation, protein carbonyl, hydroxyproline, and liver iron by 32.28,
      64.58, 136.81, and 83.55%, respectively. CONCLUSION: These findings suggest that
      the active substances present in NIME may be capable of lessening iron overload
      induced toxicity, and possibly be a useful drug for iron-overloaded diseases.

PMID- 25609152
TI  - Potent protein tyrosine phosphatase 1B (PTP1B) inhibiting constituents from
      Anoectochilus chapaensis and molecular docking studies.
AB  - CONTEXT: Anoectochilus chapaensis Gagnep. (Orchidaceae), an indigenous and
      valuable Chinese folk medicine, has been used as an antidiabetic remedy. However,
      the bioactive constituents have not been reported. OBJECTIVE: To explore potent
      protein tyrosine phosphatase 1B (PTP1B) inhibitors from the whole herbs of A.
      chapaensis for the treatment of diabetes. MATERIALS AND METHODS: The compounds
      were obtained by PTP1B bioactivity-guided isolation from the active fraction of
      ethonal extract of A. chapaensis, and elucidated by extensive spectroscopic
      methods and evaluated for their potential to inhibit PTP1B with a series of doses
      in dimethyl sulphoxide by a colorimetric assay in vitro. The Autodock program was
      used to dock the active compounds into the binding sites. RESULTS: Fifteen
      compounds were identified; epifriedelanol, friedelane, 2alpha, 3beta
      dihydroxyolean-12-en-23, 28, 30-trioic acid, dibutyl-phthalate, and 7-hydroxy-2
      methoxy-9,10-dihydrophenanthrene-1,4-dione were isolated from the genera
      Anoectochilus for the first time. All 15 compounds were tested for their
      inhibitory activity against PTP1B in vitro. Nine active compounds exhibited
      potent inhibitory effect with IC50 values of 1.16-6.21 MUM, which were comparable
      with the positive control suramin. The 3D-docking simulations showed negative
      binding energies of -7.4 to -8.5 kcal/mol and supported a high affinity to PTP1B
      residues in the pocket site, indicating that they may stabilize the open form and
      generate tighter binding to the catalytic sites of PTP1B. DISCUSSION AND
      CONCLUSION: The results clearly demonstrated that the potential active
      constituents from A. chapaensis could inhibit PTP1B, which may be mainly
      attributed to a combination of triterpenoids and flavonoids.

PMID- 25609153
TI  - Pediatric inflammatory bowel disease in Greece: 30-years experience of a single
      center.
AB  - BACKGROUND: Significant advances have been made in the care of children with
      inflammatory bowel disease (IBD). We aimed to describe the trends during the last
      3 decades in the clinical presentation, management, and outcome of pediatric IBD
      at a single center. METHODS: Medical records of children with IBD referred to a
      pediatric gastroenterology unit from January 1981 to December 2011 were reviewed
      retrospectively. RESULTS: A total of 483 children were diagnosed with IBD, with
      mean age at diagnosis of 9.6 years (range 6 months - 18 years). Ulcerative
      colitis (UC) was diagnosed in 267 (55.2%), Crohn's disease (CD) in 167 (34.5%),
      and IBD unclassified (IBDU) in 49 (10.1%). Children with UC and IBDU were younger
      than those with CD [mean age at diagnosis 9.2, 8.9, and 10.5 years respectively;
      P (UC vs. CD)<0.01 and P (IBDU vs. CD)=0.028]. Patients received 5-ASA (96.6%),
      steroids (77.0%), thiopurines (50.2%), biological agents (14%), and 10% underwent
      surgical intervention. The cohort was divided into three subgroups according to
      the date of diagnosis; Group A: 1981-1989, Group B: 1990-1999, and Group C: 2000
      2011. During the last two decades a significant increase in CD (Group A 18.5%,
      Group B 23.8%, Group C 48.8%; P<0.01) compared with the first decade with
      parallel decrease in UC (Group A 79.6%, Group B 71.9%, Group C 33.2%; P<0.001)
      was observed. CONCLUSIONS: Most children received 5-ASA, steroids, and
      immunomodulators. Patients with UC and IBDU were younger than those with CD. A
      significant increase in CD with parallel decrease in UC during the last decade
      was found.

PMID- 25609154
TI  - Early weaning by maternal prolactin inhibition leads to higher neuropeptide Y and
      astrogliosis in the hypothalamus of the adult rat offspring.
AB  - The suppression of prolactin production with bromocriptine (BRO) in the last 3 d
      of lactation reduces milk yield (early weaning) and increases the transfer of
      leptin through the milk, causing hyperleptinaemia in pups. In adulthood, several
      changes occur in the offspring as a result of metabolic programming, including
      overweight, higher visceral fat mass, hypothyroidism, hyperglycaemia, insulin
      resistance, hyperleptinaemia and central leptin resistance. In the present study,
      we investigated whether overweight rats programmed by early weaning with maternal
      BRO treatment have hypothalamic alterations in adulthood. We analysed the
      expression of neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript
      (CART), pro-opiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone
      (alpha-MSH) by immunohistochemistry in the following hypothalamic nuclei: medial
      and lateral arcuate nucleus (ARC); paraventricular nucleus (PVN); lateral
      hypothalamus (LH). Additionally, we sought to determine whether these programmed
      rats exhibited hypothalamic inflammation as indicated by astrogliosis. NPY
      immunostaining showed a denser NPY-positive fibre network in the ARC and PVN
      (+82% in both nuclei) of BRO offspring. Regarding the anorexigenic neuropeptides,
      no difference was found for CART, POMC and alpha-MSH. The number of astrocytes
      was higher in all the nuclei of BRO rats. The fibre density of glial fibrillary
      acidic protein was also increased in both medial and lateral ARC (6.06-fold
      increase and 9.13-fold increase, respectively), PVN (5.75-fold increase) and LH
      (2.68-fold increase) of BRO rats. We suggest that early weaning has a long-term
      effect on the expression of NPY as a consequence of developmental plasticity, and
      the presence of astrogliosis indicates hypothalamic inflammation that is closely
      related to overweight and hyperleptinaemia observed in our model.

PMID- 25609155
TI  - Physiological activities associated with biofilm growth in attached and suspended
      growth bioreactors under aerobic and anaerobic conditions.
AB  - This research work evaluated the biofilm succession on stone media and compared
      the biochemical changes of sludge in attached and suspended biological reactors
      operated under aerobic and anaerobic conditions. Stones incubated (30+/-2 degrees
      C) with activated sludge showed a constant increase in biofilm weight up to the
      fifth and seventh week time under anaerobic and aerobic conditions, respectively,
      where after reduction (>80%) the most probable number index of pathogen
      indicators on ninth week was recorded. Reduction in parameters such as biological
      oxygen demand (BOD) (47.7%), chemical oxygen demand (COD, 41%), nitrites (60.2%),
      nitrates (105.5%) and phosphates (58.9%) and increase in dissolved oxygen
      (176.5%) of sludge were higher in aerobic attached growth reactors as compared
      with other settings. While, considerable reductions in these values were also
      observed (BOD, 53.8%; COD, 2.8%; nitrites, 28.6%; nitrates, 31.7%; phosphates,
      41.4%) in the suspended growth system under anaerobic conditions. However, higher
      sulphate removal was observed in suspended (40.9% and 54.9%) as compared with
      biofilm reactors (28.2% and 29.3%). Six weeks biofilm on the stone media showed
      maximum physiological activities; thus, the operational conditions should be
      controlled to keep the biofilm structure similar to six-week-old biofilm, and can
      be used in fixed biofilm reactors for wastewater treatment.

PMID- 25609156
TI  - Bisphosphonate therapy: how long is long enough?

PMID- 25609157
TI  - RANKL and OPG gene polymorphisms: associations with vertebral fractures and bone
      mineral density in premenopausal systemic lupus erythematosus.
AB  - Premenopausal women with systemic lupus erythematosus (SLE) have a higher
      prevalence of low bone mineral density and vertebral fractures. Multiple genetic
      loci for osteoporotic fracture were identified in recent genome-wide association
      studies. This study provides a novel data demonstrating that receptor activator
      of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) polymorphisms likely plays an
      important role in the bone remodeling process in SLE premenopausal women.
      INTRODUCTION: The purpose of this study was to evaluate single-nucleotide
      polymorphisms (SNPs) of the RANKL, RANK, and OPG genes in premenopausal SLE
      patients and their association with sRANKL and OPG serum levels, vertebral
      fractures, and bone mineral density (BMD). METHODS: A total of 211 premenopausal
      SLE patients (American College of Rheumatology (ACR) criteria) and 154 healthy
      controls were enrolled. SNPs of RANKL 290A>G (rs2277438), OPG 1181G>C
      (rs2073618), 245T>G (rs3134069), 163A>G (rs3102735), and RANK A>G (rs3018362)
      were obtained by real-time PCR. sRANKL/OPG serum levels were determined by ELISA.
      BMD and vertebral fractures were evaluated by dual-energy X-ray absorptiometry
      (DXA). RESULTS: SLE patients and controls had similar frequencies of the RANKL
      290 G allele (p = 0.94), OPG 1181 C allele (p = 0.85), OPG 245 G allele (p =
      0.85), OPG 163 G allele (p = 0.78), and RANK G allele (p = 0.87). Further
      analysis of the SLE patients revealed that the frequency of the RANKL 290 G
      allele was lower in patients with fractures than that in patients without
      fractures (28.1 vs 46.9%, p = 0.01). In addition, the frequency of the OPG 245 G
      allele was higher in patients with low BMD than that in patients with normal BMD
      (31.4 vs 18.1%, p = 0.04). No association of OPG 1181 G>C, OPG 163 A>G, and RANK
      A>G SNPs with BMD/fractures was found. Additionally, no association was observed
      between RANKL/OPG/RANK SNPs and sRANKL/OPG serum levels. CONCLUSIONS: Our study
      provides novel data demonstrating that RANKL/OPG genetic variations appear to
      play a role in bone remodeling, particularly in its major complication, fracture,
      in premenopausal patients with SLE.

PMID- 25609159
TI  - Redox cycling behavior of individual and binary mixtures of catecholamines at
      gold microband electrode arrays.
AB  - The electrochemical redox cycling (RC) behavior of individual and binary mixtures
      of three catecholamines are investigated using gold microelectrode arrays in
      vitro. Catecholamines showed reversible or irreversible responses during RC
      depending on their oxidation products' cyclization rate. The RC behavior of the
      binary mixtures supports the disproportionation reaction of catecholamines, which
      has been previously reported, but not under RC conditions or with mixtures. This
      fundamental study provides insights on the effects of complicated mechanisms and
      kinetics on RC and sets the foundation for future applications of RC for in vivo
      multi-neurotransmitter analysis. 

PMID- 25609158
TI  - Early B-cell factor 3 (EBF3) is a novel tumor suppressor gene with promoter
      hypermethylation in pediatric acute myeloid leukemia.
AB  - BACKGROUND: Pediatric acute myeloid leukemia (AML) comprises up to 20% of all
      childhood leukemia. Recent research shows that aberrant DNA methylation
      patterning may play a role in leukemogenesis. The epigenetic silencing of the
      EBF3 locus is very frequent in glioblastoma. However, the expression profiles and
      molecular function of EBF3 in pediatric AML is still unclear. METHODS: Twelve
      human acute leukemia cell lines, 105 pediatric AML samples and 30 normal bone
      marrow/idiopathic thrombocytopenic purpura (NBM/ITP) control samples were
      analyzed. Transcriptional level of EBF3 was evaluated by semi-quantitative and
      real-time PCR. EBF3 methylation status was determined by methylation specific PCR
      (MSP) and bisulfite genomic sequencing (BGS). The molecular mechanism of EBF3 was
      investigated by apoptosis assays and PCR array analysis. RESULTS: EBF3 promoter
      was hypermethylated in 10/12 leukemia cell lines. Aberrant EBF3 methylation was
      observed in 42.9% (45/105) of the pediatric AML samples using MSP analysis, and
      the BGS results confirmed promoter methylation. EBF3 expression was decreased in
      the AML samples compared with control. Methylated samples revealed similar
      survival outcomes by Kaplan-Meier survival analysis. EBF3 overexpression
      significantly inhibited cell proliferation and increased apoptosis. Real-time PCR
      array analysis revealed 93 dysregulated genes possibly implicated in the
      apoptosis of EBF3-induced AML cells. CONCLUSION: In this study, we firstly
      identified epigenetic inactivation of EBF3 in both AML cell lines and pediatric
      AML samples for the first time. Our findings also showed for the first time that
      transcriptional overexpression of EBF3 could inhibit proliferation and induce
      apoptosis in AML cells. We identified 93 dysregulated apoptosis-related genes in
      EBF3-overexpressing, including DCC, AIFM2 and DAPK1. Most of these genes have
      never been related with EBF3 over expression. These results may provide new
      insights into the molecular mechanism of EBF3-induced apoptosis; however, further
      research will be required to determine the underlying details. Our findings
      suggest that EBF3 may act as a putative tumor suppressor gene in pediatric AML.

PMID- 25609160
TI  - PET imaging of oncolytic VSV expressing the mutant HSV-1 thymidine kinase
      transgene in a preclinical HCC rat model.
AB  - Hepatocellular carcinoma (HCC) is the most predominant form of liver cancer and
      the third leading cause of cancer-related death worldwide. Due to the relative
      ineffectiveness of conventional HCC therapies, oncolytic viruses have emerged as
      novel alternative treatment agents. Our previous studies have demonstrated
      significant prolongation of survival in advanced HCC in rats after oncolytic
      vesicular stomatitis virus (VSV) treatment. In this study, we aimed to establish
      a reporter system to reliably and sensitively image VSV in a clinically relevant
      model of HCC for clinical translation. To this end, an orthotopic, unifocal HCC
      model in immune-competent Buffalo rats was employed to test a recombinant VSV
      vector encoding for an enhanced version of the herpes simplex virus 1 (HSV-1)
      thymidine kinase (sr39tk) reporter, which would allow the indirect detection of
      VSV via positron emission tomography (PET). The resulting data revealed specific
      tracer uptake in VSV-HSV1-sr39tk-treated tumors. Further characterization of the
      VSV-HSV1-sr39tk vector demonstrated its optimal detection time-point after
      application and its detection limit via PET. In conclusion, oncolytic VSV
      expressing the HSV1-sr39tk reporter gene allows for highly sensitive in vivo
      imaging via PET. Therefore, this imaging system may be directly translatable and
      beneficial in further clinical applications. 

PMID- 25609161
TI  - Hyperthermic intraperitoneal chemotherapy for ovarian cancer: is there a role?

PMID- 25609162
TI  - Single-site robotic surgery in gynecologic cancer: a pilot study.
AB  - OBJECTIVE: To discuss the feasibility of single-site robotic surgery for benign
      gynecologic tumors and early stage gynecologic cancers. METHODS: In this single
      institution, prospective analysis, we analyzed six patients who had undergone
      single-site robotic surgery between December 2013 and August 2014. Surgery was
      performed using the da Vinci Si Surgical System. Patient characteristics and
      surgical outcomes were analyzed. RESULTS: Single-site robotic surgery was
      performed successfully in all six cases. The median patient age was 48 years, and
      the median body mass index was 25.5 kg/m2 (range, 22 to 33 kg/m2). The median
      total operative time was 211 minutes, and the median duration of intracorporeal
      vaginal cuff suturing was 32 minutes (range, 22 to 47 minutes). The median
      duration of pelvic lymph node dissection was 31 minutes on one side and 27
      minutes on the other side. Patients' postoperative courses were uneventful. The
      median postoperative hospital stay was 4 days. No postoperative complications
      occurred. CONCLUSION: When used to treat benign gynecologic tumors and early
      stage gynecologic cancers, the single-site da Vinci robotic surgery is feasible,
      safe, and produces favorable surgical outcomes.

PMID- 25609164
TI  - Are we ready for conservative treatment in ovarian cancer?

PMID- 25609163
TI  - Asian Society of Gynecologic Oncology International Workshop 2014.
AB  - The Asian Society of Gynecologic Oncology International Workshop 2014 on
      gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to
      24th August 2014. A total of 179 participants from 17 countries participated in
      the workshop, and the up-to-date findings on the management of gynecologic
      cancers were presented and discussed. This meeting focused on the new trends in
      the management of cervical cancer, fertility-sparing management of gynecologic
      cancers, surgical management of gynecologic cancers, and recent advances in
      translational research on gynecologic cancers. 

PMID- 25609165
TI  - Endometriosis: bright future for a cloudy past?
AB  - New estrogen receptor ligands arrest endometriotic implant survival but spare
      reproductive cycles in a mouse model of endometriosis, thus forging a path to new
      treatment options (Zhao et al., this issue). 

PMID- 25609166
TI  - Cancer and the gut microbiota: an unexpected link.
AB  - Changes in the interactions among the gut microbiota, intestinal epithelium, and
      host immune system are associated with many diseases, including cancer. We
      discuss how environmental factors infuence this cross-talk during oncogenesis and
      tumor progression and how manipulations of the gut microbiota might improve the
      clinical activity of anticancer agents.

PMID- 25609167
TI  - Surface-enhanced resonance Raman scattering nanostars for high-precision cancer
      imaging.
AB  - The inability to visualize the true extent of cancers represents a significant
      challenge in many areas of oncology. The margins of most cancer types are not
      well demarcated because the cancer diffusely infiltrates the surrounding tissues.
      Furthermore, cancers may be multifocal and characterized by the presence of
      microscopic satellite lesions. Such microscopic foci represent a major reason for
      persistence of cancer, local recurrences, and metastatic spread, and are usually
      impossible to visualize with currently available imaging technologies. An imaging
      method to reveal the true extent of tumors is desired clinically and surgically.
      We show the precise visualization of tumor margins, microscopic tumor invasion,
      and multifocal locoregional tumor spread using a new generation of surface
      enhanced resonance Raman scattering (SERRS) nanoparticles, which are termed SERRS
      nanostars. The SERRS nanostars feature a star-shaped gold core, a Raman reporter
      resonant in the near-infrared spectrum, and a primer-free silication method. In
      genetically engineered mouse models of pancreatic cancer, breast cancer, prostate
      cancer, and sarcoma, and in one human sarcoma xenograft model, SERRS nanostars
      enabled accurate detection of macroscopic malignant lesions, as well as
      microscopic disease, without the need for a targeting moiety. Moreover, the
      sensitivity (1.5 fM limit of detection) of SERRS nanostars allowed imaging of
      premalignant lesions of pancreatic and prostatic neoplasias. High sensitivity and
      broad applicability, in conjunction with their inert gold-silica composition,
      render SERRS nanostars a promising imaging agent for more precise cancer imaging
      and resection. 

PMID- 25609170
TI  - Endoscopic variceal ligation in children with extrahepatic portal vein
      thrombosis: long-term follow up of 2 cases.

PMID- 25609168
TI  - Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model
      of autism.
AB  - Mouse models of neuropsychiatric diseases provide a platform for mechanistic
      understanding and development of new therapies. We previously demonstrated that
      knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2),
      in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome,
      displays many features that parallel those of the human disorder. Because CDFE
      has high penetrance for autism spectrum disorder (ASD), we performed an in vivo
      screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice
      and found that acute administration of the neuropeptide oxytocin improved social
      deficits. We found a decrease in the number of oxytocin immunoreactive neurons in
      the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an
      overall decrease in brain oxytocin levels. Administration of a selective
      melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also
      acutely rescued the social deficits, an effect blocked by an oxytocin antagonist.
      We confirmed that oxytocin neurons mediated the behavioral improvement by
      activating endogenous oxytocin neurons in the paraventricular hypothalamus with
      Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we
      showed that chronic early postnatal treatment with oxytocin led to more lasting
      behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data
      demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and
      suggest that there may be critical developmental windows for optimal treatment to
      rectify this deficit. 

PMID- 25609171
TI  - Experiences with the implementation of a national teaching qualification in
      university medical centres and veterinary medicine in the Netherlands.
AB  - In 2008, a compulsory national basic teaching qualification was introduced for
      all university teachers in the Netherlands. At that time all eight University
      Medical Centres (UMCs) and the only Faculty of Veterinary Medicine had adopted or
      were setting up teacher development programmes. This study explores how these
      programmes relate to each other and to the basic teaching qualification. To
      gather information on teacher development programmes in the UMCs and the
      Veterinary Medicine Faculty an online survey was filled out by teacher
      development representatives from each of them. The programmes had main features
      in common (e.g. competency based and portfolio assessment), but differed somewhat
      in contents according to the local situation. Importantly, they had all been
      formally accepted as equivalent to the basic teaching qualification. We consider
      the freedom to tailor the qualifications to the medical context as well as to the
      local situation of the UMCs and the Veterinary Medicine Faculty one of the major
      success factors and the well-established collaboration between teacher
      development representatives of the UMCs and the Faculty of Veterinary Medicine as
      another. Challenges for the future include embedding the teacher development
      programmes in the institutional organizations and maintaining and further
      developing the programmes and the competencies of the qualified teachers, e.g. in
      a senior qualification. 

PMID- 25609169
TI  - Dual suppression of estrogenic and inflammatory activities for targeting of
      endometriosis.
AB  - Estrogenic and inflammatory components play key roles in a broad range of
      diseases including endometriosis, a common estrogen-dependent gynecological
      disorder in which endometrial tissue creates inflammatory lesions at extrauterine
      sites, causing pelvic pain and reduced fertility. Current medical therapies focus
      primarily on reducing systemic levels of estrogens, but these are of limited
      effectiveness and have considerable side effects. We developed estrogen receptor
      (ER) ligands, chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS), which
      showed strong ER-dependent anti-inflammatory activity in a preclinical model of
      endometriosis that recapitulates the estrogen dependence and inflammatory
      responses of the disease in immunocompetent mice and in primary human
      endometriotic stromal cells in culture. Estrogen-dependent phenomena, including
      cell proliferation, cyst formation, vascularization, and lesion growth, were all
      arrested by CLI or OBHS, which prevented lesion expansion and also elicited
      regression of established lesions, suppressed inflammation, angiogenesis, and
      neurogenesis in the lesions, and interrupted crosstalk between lesion cells and
      infiltrating macrophages. Studies in ERalpha or ERbeta knockout mice indicated
      that ERalpha is the major mediator of OBHS effectiveness and ERbeta is dominant
      in CLI actions, implying involvement of both ERs in endometriosis. Neither ligand
      altered estrous cycling or fertility at doses that were effective for suppression
      of endometriosis. Hence, CLI and OBHS are able to restrain endometriosis by dual
      suppression of the estrogen-inflammatory axis. Our findings suggest that these
      compounds have the desired characteristics of preventive and therapeutic agents
      for clinical endometriosis and possibly other estrogen-driven and inflammation
      promoted disorders. 

PMID- 25609172
TI  - Data analysis in medical education research: a multilevel perspective.
AB  - A substantial part of medical education research focuses on learning in teams
      (e.g., departments, problem-based learning groups) or centres (e.g., clinics,
      institutions) that are followed over time. Individual students or employees
      sharing the same team or centre tend to be more similar in learning than students
      or employees from different teams or centres. In other words, when students or
      employees are nested within teams or centres, there is a within-team or within
      centre correlation that should be taken into account in the analysis of data
      obtained from individuals in these teams or centres. Further, when individuals
      are measured several times on the same performance (or other) variable, these
      repeated measurements tend to be correlated, that is: we are dealing with an
      intra-individual correlation that should be taken into account when analyzing
      data obtained from these individuals. In such a study context, many researchers
      resort to methods that cannot account for intra-team and/or intra-individual
      correlation and this may result in incorrect conclusions with regard to effects
      and relations of interest. This comparison paper presents the benefits which
      result from adopting a proper multilevel perspective on the conceptualization and
      estimation of effects and relations of interest. 

PMID- 25609173
TI  - Correction: Modular and orthogonal synthesis of hybrid polymers and networks.

PMID- 25609174
TI  - Multimorbidity, health care utilization and costs in an elderly community
      dwelling population: a claims data based observational study.
AB  - BACKGROUND: Chronic conditions and multimorbidity have become one of the main
      challenges in health care worldwide. However, data on the burden of
      multimorbidity are still scarce. The purpose of this study is to examine the
      association between multimorbidity and the health care utilization and costs in
      the Swiss community-dwelling population, taking into account several
      sociodemographic factors. METHODS: The study population consists of 229'493
      individuals aged 65 or older who were insured in 2013 by the Helsana Group, the
      leading health insurer in Switzerland, covering all 26 Swiss cantons.
      Multimorbidity was defined as the presence of two or more chronic conditions of a
      list of 22 conditions that were identified using an updated measure of the
      Pharmacy-based Cost Group model. The number of consultations (total and divided
      by primary care physicians and specialists), the number of different physicians
      contacted, the type of physician contact (face-to-face, phone, and home visits),
      the number of hospitalisations and the length of stay were assessed separately
      for the multimorbid and non-multimorbid sample. The costs (total and divided by
      inpatient and outpatient costs) covered by the compulsory health insurance were
      calculated for both samples. Multiple linear regression modelling was conducted
      to adjust for influencing factors: age, sex, linguistic region, purchasing power,
      insurance plan, and nursing dependency. RESULTS: Prevalence of multimorbidity was
      76.6%. The mean number of consultations per year was 15.7 in the multimorbid
      compared to 4.4 in the non-multimorbid sample. Total costs were 5.5 times higher
      in multimorbid patients. Each additional chronic condition was associated with an
      increase of 3.2 consultations and increased costs of 33%. Strong positive
      associations with utilization and costs were also found for nursing dependency.
      Multimorbid patients were 5.6 times more likely to be hospitalised. Furthermore,
      results revealed a significant age-gender interaction and a socioeconomic
      gradient. CONCLUSIONS: Multimorbidity is associated with substantial higher
      health care utilization and costs in Switzerland. Quantified data on the current
      burden of multimorbidity are fundamental for the management of patients in health
      service delivery systems and for health care policy debates about resource
      allocation. Strategies for a better coordination of multimorbid patients are
      urgently needed.

PMID- 25609175
TI  - A DFT study of the effect of OH groups on the optical, electronic, and structural
      properties of TiO2 nanoparticles.
AB  - The effects of on-surface OH groups on the structural and optical properties of
      small TiO2 particles have been studied in order to obtain knowledge about the
      optical behaviour of the TiO2 nanoparticles in solutions. The standard density
      functional theory was used to model the structural changes, and time-dependent
      density functional theory was used to address the changes in the photoabsorption
      characteristics of an anatase-structured (TiO2)16 cluster. It was shown that the
      OH groups can alter both the geometric and electronic structure of the clusters,
      resulting in changes in the optical properties. The large blue shift, obtained in
      earlier calculations for TiO2 nanoparticles as compared with bulk TiO2, is shown
      to be reduced by OH adsorption. 

PMID- 25609176
TI  - A randomized controlled trial of endoscopic steroid injection for prophylaxis of
      esophageal stenoses after extensive endoscopic submucosal dissection.
AB  - BACKGROUND: Esophageal stenosis following endoscopic submucosal dissection (ESD)
      is a serious adverse event that makes subsequent management more difficult.
      METHODS: This parallel, randomized, controlled, open-label study was designed to
      examine whether local steroid injection is an effective prophylactic treatment
      for esophageal stenoses following extensive ESD. This single center trial was
      conducted at the Keiyukai Hospital, a tertiary care center for gastrointestinal
      disease in Japan [University Hospital Medical Network Clinical Trial Registry
      (UMIN-CTR) on 15 September 2011 (UMIN000006327)]. Thirty-two patients with
      mucosal defects involving >=75% of the esophageal circumference were randomized
      to receive a single dose of triamcinolone acetonide injections (n = 16) or be
      treated conventionally (n = 16). The primary outcome was the frequency of
      stricture requiring endoscopic dilatation; the surrogate primary endpoint was the
      number of dilatation sessions needed. Secondary outcomes included adverse event
      rates, the minimum diameter of the stenotic area and the duration of the course
      of dilatation treatments. RESULTS: The frequency of stricture was not
      significantly different between the groups because of insufficient statistical
      power, but the number of dilatation sessions required was significantly less in
      the steroid group (6.1 sessions [95% confidence interval, CI 2.8-9.4] versus 12.5
      [95% CI 7.1-17.9] sessions in the control group; P = 0.04). The perforation rate
      was similar in both groups. The minimum diameter of stenotic lumens was
      significantly greater in the treatment group than controls (11.0 mm versus 7.1
      mm, respectively; P = 0.01). The perforation rate was not significantly different
      between the groups (1.0% versus 0.5% in the treatment and control group,
      respectively). Steroid injection was effective in cases of mucosal defects
      encompassing the entire esophageal circumference. CONCLUSIONS: Prophylactic
      endoscopic steroid injection appears to be a safe means of relieving the severity
      of esophageal stenoses following extensive ESD.

PMID- 25609177
TI  - The proteins of exocytosis: lessons from the sperm model.
AB  - Exocytosis is a highly regulated process that consists of multiple functionally,
      kinetically and/or morphologically definable stages such as recruitment,
      targeting, tethering and docking of secretory vesicles with the plasma membrane,
      priming of the fusion machinery and calcium-triggered membrane fusion. After
      fusion, the membrane around the secretory vesicle is incorporated into the plasma
      membrane and the granule releases its contents. The proteins involved in these
      processes belong to several highly conserved families: Rab GTPases, SNAREs
      (soluble NSF-attachment protein receptors), alpha-SNAP (alpha-NSF attachment
      protein), NSF (N-ethylmaleimide-sensitive factor), Munc13 and -18, complexins and
      synaptotagmins. In the present article, the molecules of exocytosis are reviewed,
      using human sperm as a model system. Sperm exocytosis is driven by isoforms of
      the same proteinaceous fusion machinery mentioned above, with their functions
      orchestrated in a hierarchically organized and unidirectional signalling cascade.
      In addition to the universal exocytosis regulator calcium, this cascade includes
      other second messengers such as diacylglycerol, inositol 1,4,5-trisphosphate and
      cAMP, as well as the enzymes that synthesize them and their target proteins. Of
      special interest is the cAMP-binding protein Epac (exchange protein directly
      activated by cAMP) due in part to its enzymatic activity towards Rap. The
      activation of Epac and Rap leads to a highly localized calcium signal which,
      together with assembly of the SNARE complex, governs the final stages of
      exocytosis. The source of this releasable calcium is the secretory granule
      itself. 

PMID- 25609178
TI  - HRCT score and serum ferritin level are factors associated to the 1-year
      mortality of acute interstitial lung disease in clinically amyopathic
      dermatomyositis patients.
AB  - The aim of this study is to evaluate the factors associated to 1-year mortality
      in clinically amyopathic dermatomyositis (CADM) patients with acute interstitial
      lung disease (ILD). A single center of 37 cases of Chinese patients with CADM was
      reviewed retrospectively in Renji hospital. All CADM patients were diagnosed with
      ILD; there were 24 cases of acute interstitial pneumonia (AIP) and 13 cases of
      acute exacerbation of non-acute interstitial pneumonia non-AIP. The clinical
      features, including blood tests, chest high-resolution computed tomography (HRCT)
      score, and lung function, were analyzed, respectively. Neutrophil lymphocyte
      ratio (NLR), serum ferritin level, serum lactate dehydrogenase (LDH) level, and
      HRCT score were statistically significant factors on univariate analysis.
      Multivariate analysis revealed that the overall HRCT score (HR 1.134, 95 %
      confidence interval 1.009-1.275, P = 0.017) and serum ferritin level (HR 1.001,
      95 % confidence interval 1.002-1.007, P = 0.010) were independently significant
      factors of 1-year mortality. C statistic value of HRCT score (c statistic value
      0.867, P < 0.0001) and serum ferritin level (c statistic value 0.808, P = 0.002)
      were statistically significant in the classification of non-survivors. Patients
      with calcineurin inhibitor presented a better outcome than those without
      calcineurin inhibitor (log-rank test, P = 0.006). HRCT score and serum ferritin
      level are factors associated to the 1-year mortality of acute ILD in CADM
      patients. Calcineurin inhibitor might improve the outcome of CADM patients with
      acute ILD.

PMID- 25609180
TI  - Indian government outlines plans to tighten tobacco control laws.

PMID- 25609182
TI  - Low toxicity of deoxynivalenol-3-glucoside in microbial cells.
AB  - Host plants excrete a glucosylation enzyme onto the plant surface that changes
      mycotoxins derived from fungal secondary metabolites to glucosylated products.
      Deoxynivalenol-3-glucoside (DON3G) is synthesized by grain uridine diphosphate
      glucosyltransferase, and is found worldwide, although information on its toxicity
      is lacking. Here, we conducted growth tests and DNA microarray analysis to
      elucidate the characteristics of DON3G. The Saccharomyces cerevisiae PDR5 mutant
      strain exposed to DON3G demonstrated similar growth to the dimethyl sulfoxide
      control, and DNA microarray analysis revealed limited differences. Only 10 genes
      were extracted, and the expression profile of stress response genes was similar
      to that of DON, in contrast to metabolism genes like SER3, which encodes 3
      phosphoglycerate dehydrogenase. Growth tests with Chlamydomonas reinhardtii also
      showed a similar growth rate to the control sample. These results suggest that
      DON3G has extremely low toxicity to these cells, and the glucosylation of
      mycotoxins is a useful protective mechanism not only for host plants, but also
      for other species. 

PMID- 25609181
TI  - Shiga toxin 2-induced endoplasmic reticulum stress is minimized by activated
      protein C but does not correlate with lethal kidney injury.
AB  - Enterohemorrhagic Escherichia coli produce ribotoxic Shiga toxins (Stx), which
      are responsible for kidney injury and development of hemolytic uremic syndrome.
      The endoplasmic reticulum (ER) stress response is hypothesized to induce
      apoptosis contributing to organ injury; however, this process has been described
      only in vitro. ER stress marker transcripts of spliced XBP1 (1.78-fold), HSP40
      (4.45-fold) and CHOP (7.69-fold) were up-regulated early in kidneys of Stx2
      challenged mice compared to saline controls. Anti-apoptotic Bcl2 decreased (-2.41
      fold vs. saline) and pro-apoptotic DR5 increased (6.38-fold vs. saline) at later
      time points. Cytoprotective activated protein C (APC) reduced early CHOP
      expression (-3.3-fold vs. untreated), increased later Bcl2 expression (5.8-fold
      vs. untreated), and had early effects on survival but did not alter DR5
      expression. Changes in kidney ER stress and apoptotic marker transcripts were
      observed in Stx2-producing C. rodentium challenged mice compared to mice infected
      with a non-toxigenic control strain. CHOP (4.14-fold) and DR5 (2.81-fold) were
      increased and Bcl2 (-1.65-fold) was decreased. APC reduced CHOP expression and
      increased Bcl2 expression, but did not alter mortality. These data indicate that
      Stx2 induces renal ER stress and apoptosis in murine models of Stx2-induced
      kidney injury, but decreasing these processes alone was not sufficient to alter
      survival outcome. 

PMID- 25609183
TI  - Diversification of ergot alkaloids in natural and modified fungi.
AB  - Several fungi in two different families--the Clavicipitaceae and the
      Trichocomaceae--produce different profiles of ergot alkaloids, many of which are
      important in agriculture and medicine. All ergot alkaloid producers share early
      steps before their pathways diverge to produce different end products. EasA, an
      oxidoreductase of the old yellow enzyme class, has alternate activities in
      different fungi resulting in branching of the pathway. Enzymes beyond the branch
      point differ among lineages. In the Clavicipitaceae, diversity is generated by
      the presence or absence and activities of lysergyl peptide synthetases, which
      interact to make lysergic acid amides and ergopeptines. The range of ergopeptines
      in a fungus may be controlled by the presence of multiple peptide synthetases as
      well as by the specificity of individual peptide synthetase domains. In the
      Trichocomaceae, diversity is generated by the presence or absence of the prenyl
      transferase encoded by easL (also called fgaPT1). Moreover, relaxed specificity
      of EasL appears to contribute to ergot alkaloid diversification. The profile of
      ergot alkaloids observed within a fungus also is affected by a delayed flux of
      intermediates through the pathway, which results in an accumulation of
      intermediates or early pathway byproducts to concentrations comparable to that of
      the pathway end product. 

PMID- 25609179
TI  - Dietary animal and plant protein intakes and their associations with obesity and
      cardio-metabolic indicators in European adolescents: the HELENA cross-sectional
      study.
AB  - BACKGROUND: Previous studies suggest that dietary protein might play a beneficial
      role in combating obesity and its related chronic diseases. Total, animal and
      plant protein intakes and their associations with anthropometry and serum
      biomarkers in European adolescents using one standardised methodology across
      European countries are not well documented. OBJECTIVES: To evaluate total, animal
      and plant protein intakes in European adolescents stratified by gender and age,
      and to investigate their associations with cardio-metabolic indicators
      (anthropometry and biomarkers). METHODS: The current analysis included 1804
      randomly selected adolescents participating in the HELENA study (conducted in
      2006-2007) aged 12.5-17.5 y (47% males) who completed two non-consecutive
      computerised 24-h dietary recalls. Associations between animal and plant protein
      intakes, and anthropometry and serum biomarkers were examined with General linear
      Model multivariate analysis. RESULTS: Average total protein intake exceeded the
      recommendations of World Health Organization and European Food Safety Authority.
      Mean total protein intake was 96 g/d (59% derived from animal protein). Total,
      animal and plant protein intakes (g/d) were significantly lower in females than
      in males and total and plant protein intakes were lower in younger participants
      (12.5-14.9 y). Protein intake was significantly lower in underweight subjects and
      higher in obese ones; the direction of the relationship was reversed after
      adjustments for body weight (g/(kg.d)). The inverse association of plant protein
      intakes was stronger with BMI z-score and body fat percentage (BF%) compared to
      animal protein intakes. Additionally, BMI and BF% were positively associated with
      energy percentage of animal protein. CONCLUSIONS: This sample of European
      adolescents appeared to have adequate total protein intake. Our findings suggest
      that plant protein intakes may play a role in preventing obesity among European
      adolescents. Further longitudinal studies are needed to investigate the potential
      beneficial effects observed in this study in the prevention of obesity and
      related chronic diseases.

PMID- 25609185
TI  - Arranging marriage; negotiating risk: genetics and society in Qatar.
AB  - This paper considers how the globalized discourse of genetic risk in cousin
      marriage is shaped, informed and taken up in local moral worlds within the
      context of Qatar. This paper investigates the way Qataris are negotiating the
      discourse on genetics and risk. It is based on data from ongoing ethnographic
      research in Qatar and contributes to anthropological knowledge about this
      understudied country. Participants were ambivalent about genetic risks and often
      pointed to other theories of causation in relation to illness and disability. The
      discourse on genetic risk associated with marrying in the family was familiar,
      but for some participants the benefits of close marriage outweighed potential
      risks. Furthermore, the introduction of mandatory pre-marital screening gave
      participants confidence that risks were monitored and minimized. 

PMID- 25609184
TI  - Joint eQTL assessment of whole blood and dura mater tissue from individuals with
      Chiari type I malformation.
AB  - BACKGROUND: Expression quantitative trait loci (eQTL) play an important role in
      the regulation of gene expression. Gene expression levels and eQTLs are expected
      to vary from tissue to tissue, and therefore multi-tissue analyses are necessary
      to fully understand complex genetic conditions in humans. Dura mater tissue
      likely interacts with cranial bone growth and thus may play a role in the
      etiology of Chiari Type I Malformation (CMI) and related conditions, but it is
      often inaccessible and its gene expression has not been well studied. A genetic
      basis to CMI has been established; however, the specific genetic risk factors are
      not well characterized. RESULTS: We present an assessment of eQTLs for whole
      blood and dura mater tissue from individuals with CMI. A joint-tissue analysis
      identified 239 eQTLs in either dura or blood, with 79% of these eQTLs shared by
      both tissues. Several identified eQTLs were novel and these implicate genes
      involved in bone development (IPO8, XYLT1, and PRKAR1A), and ribosomal pathways
      related to marrow and bone dysfunction, as potential candidates in the
      development of CMI. CONCLUSIONS: Despite strong overall heterogeneity in
      expression levels between blood and dura, the majority of cis-eQTLs are shared by
      both tissues. The power to detect shared eQTLs was improved by using an
      integrative statistical approach. The identified tissue-specific and shared eQTLs
      provide new insight into the genetic basis for CMI and related conditions.

PMID- 25609186
TI  - Exploring the success of an integrated primary care partnership: a longitudinal
      study of collaboration processes.
AB  - BACKGROUND: Forming partnerships is a prominent strategy used to promote
      integrated service delivery across health and social service systems. Evidence
      about the collaboration process upon which partnerships evolve has rarely been
      addressed in an integrated-care setting. This study explores the longitudinal
      relationship of the collaboration process and the influence on the final
      perceived success of a partnership in such a setting. The collaboration process
      through which partnerships evolve is based on a conceptual framework which
      identifies five themes: shared ambition, interests and mutual gains, relationship
      dynamics, organisational dynamics and process management. METHODS: Fifty-nine out
      of 69 partnerships from a national programme in the Netherlands participated in
      this survey study. At baseline, 338 steering committee members responded, and
      they returned 320 questionnaires at follow-up. Multiple-regression-analyses were
      conducted to explore the relationship between the baseline as well as the change
      in the collaboration process and the final success of the partnerships. RESULTS:
      Mutual gains and process management were the most significant baseline predictors
      for the final success of the partnership. A positive change in the relationship
      dynamics had a significant effect on the final success of a partnership.
      CONCLUSIONS: Insight into the collaboration process of integrated primary care
      partnerships offers a potentially powerful way of predicting their success. Our
      findings underscore the importance of monitoring the collaboration process during
      the development of the partnerships in order to achieve their full collaborative
      advantage.

PMID- 25609187
TI  - Relativistic quantum metrology in open system dynamics.
AB  - Quantum metrology studies the ultimate limit of precision in estimating a
      physical quantity if quantum strategies are exploited. Here we investigate the
      evolution of a two-level atom as a detector which interacts with a massless
      scalar field using the master equation approach for open quantum system. We
      employ local quantum estimation theory to estimate the Unruh temperature when
      probed by a uniformly accelerated detector in the Minkowski vacuum. In
      particular, we evaluate the Fisher information (FI) for population measurement,
      maximize its value over all possible detector preparations and evolution times,
      and compare its behavior with that of the quantum Fisher information (QFI). We
      find that the optimal precision of estimation is achieved when the detector
      evolves for a long enough time. Furthermore, we find that in this case the FI for
      population measurement is independent of initial preparations of the detector and
      is exactly equal to the QFI, which means that population measurement is optimal.
      This result demonstrates that the achievement of the ultimate bound of precision
      imposed by quantum mechanics is possible. Finally, we note that the same
      configuration is also available to the maximum of the QFI itself. 

PMID- 25609188
TI  - Lucas and patriotism in mid-eighteenth century Ireland.
AB  - This paper explores the extent to which Charles Lucas can be described as a
      typical patriot in mid-eighteenth century Ireland. The political ideas and
      practices of Irish patriots of the mid-eighteenth century belong to broad
      spectrum including opposition MPs, anti-Catholic rhetoricians and questioners of
      the usefulness of the penal laws, economic pamphleteers and individuals
      interested in recovering Ireland's history and antiquities. Lucas was significant
      in that he sometimes inhabited all of these political and cultural guises, but
      also mobilised the Dublin public in political campaigns and was striking in his
      voluminous output in newspapers and pamphlets.

PMID- 25609189
TI  - Modulation of microporous/mesoporous structures in self-templated cobalt-silica.
AB  - Finite control of pore size distributions is a highly desired attribute when
      producing porous materials. While many methodologies strive to produce such
      materials through one-pot strategies, oftentimes the pore structure requires post
      treatment modification. In this study, modulation of pore size in cobalt-silica
      systems was investigated by a novel, non-destructive, self-templated method.
      These systems were produced from two cobalt-containing silica starting materials
      which differed by extent of condensation. These starting materials, sol (SG') and
      xerogel (XG'), were mixed with pure silica sol to produce materials containing 5
      40 mol% Co. The resultant SG-series materials exhibited typical attributes for
      cobalt-silica systems: mesoporous characteristics developed at high cobalt
      concentrations, coinciding with Co3O4 formation; whereas, in the XG-series
      materials, these mesoporous characteristics were extensively suppressed. Based on
      an examination of the resultant materials a mechanism describing the pore size
      formation and modulation of the two systems was proposed. Pore size modulation in
      the XG-series was caused, in part, by the cobalt source acting as an autogenous
      template for the condensation of the silica network. These domains could be
      modified when wetted, allowing for the infiltration and subsequent condensation
      of silica oligomers into the pre-formed, mesoporous cages, leading to a reduction
      in the mesoporous content of the final product.

PMID- 25609190
TI  - Neoadjuvant intra-arterial chemotherapy in patients with primary lacrimal adenoid
      cystic carcinoma.
AB  - BACKGROUND: We describe four cases of primary lacrimal adenoid cystic carcinoma
      (ACC) treated with neoadjuvant intra-arterial chemotherapy (NAIC). METHODS: The
      outcomes and complications of NAIC were reviewed. Several treatment-related local
      and/or systemic complications were noted. RESULTS: One patient experienced
      ipsilateral eyelid and eyeball necrosis and permanent facial palsy; the second
      patient developed ipsilateral facial swelling and jaw claudication; and the third
      patient had febrile neutropenia, cellulitis, and phlebitis. These three patients
      underwent total exenteration. The fourth patient experienced neutropenia and
      thrombocytopenia and underwent tumour removal without exenteration. All patients
      were followed for more than 4 years and were alive at the last follow-up.
      CONCLUSION: Neoadjuvant intra-arterial chemotherapy may be an alternative
      treatment that will improve the survival rate of ACC. However, careful and close
      observation is needed to minimise the risk of side effects. Further
      investigations are needed to justify the use of chemotherapy-related treatments
      and the associated costs.

PMID- 25609191
TI  - Erratum to: Autosomal recessive lissencephaly with cerebellar hypoplasia is
      associated with a loss-of-function mutation in CDK5.

PMID- 25609192
TI  - Difficulty distinguishing benign notochordal cell tumor from chordoma further
      suggests a link between them.
AB  - BACKGROUND: Much discussion about benign notochordal cell tissue in vertebrae has
      centered on the nature of its relationship, if any, to chordoma. Often referred
      to as benign notochordal cell tumors (BNCTs), these lesions have unique
      morphological features, however, differentiating between notochordal cells in
      discs, BNCT, and chordoma can be difficult. They are described as radiologically
      distinct from chordoma, with lysis, contrast enhancement, and a soft tissue mass
      indicating chordoma. METHODS: All chordomas diagnosed at our institution, the
      Istituto Ortopedico Rizzoli (Bologna, Italy), prior to 2008 were reviewed,
      yielding 174 cases. Five were limited to bone; one was a recurrent chordoma
      without original data available. The remaining four were re-evaluated in detail.
      RESULTS: There were three women and one man, aged 33-57 years (mean, 48 years).
      Two were BNCTs and two were mixed lesions containing BNCT and chordoma. On
      computed tomography, all were radiopaque with areas of lysis. One BNCT was
      heterogeneous on magnetic resonance imaging, enhancing after contrast.
      Microscopically, one BNCT had a well-defined cystic area with a sclerotic border.
      The other had a minute atypical area; it recurred as chordoma. The mixed lesions
      had areas of definitive BNCT, definitive chordoma, and atypical areas that did
      not meet the criteria for either. The atypical areas in all three cases 'blended'
      with areas of chordoma or BNCT. CONCLUSION: These cases illustrate the ongoing
      challenges in differentiating between BNCT and chordoma. All had unique imaging
      features; three had atypical microscopic areas blending with BNCT or chordoma,
      strengthening the argument for a relationship between the two entities and
      supporting the idea that some BNCTs may progress to chordoma. Our study dispels
      the notion that any single radiologic criterion used to distinguish between
      chordoma and BNCT is reliable, opening the discussion as to whether or how to
      monitor BNCTs.

PMID- 25609193
TI  - Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2
      diabetes: a randomised, double-blind, phase 3, non-inferiority study.
AB  - BACKGROUND: Trelagliptin is a novel once-weekly oral DPP-4 inhibitor. We assessed
      the efficacy and safety of trelagliptin versus the daily oral DPP-4 inhibitor
      alogliptin in Japanese patients with type 2 diabetes. METHODS: We did a
      randomised, double-blind, active-controlled, parallel-group, phase 3, non
      inferiority study at 26 sites in Japan. We included individuals with type 2
      diabetes inadequately controlled by diet and exercise. We randomly assigned
      patients (2:2:1) to receive trelagliptin (100 mg) once per week, alogliptin (25
      mg) once per day, or placebo for 24 weeks. Randomisation was done electronically
      and independently from the study with permuted blocks of ten patients. Patients
      and clinicians were masked to group assignment. Patients in the trelagliptin
      group were given trelagliptin once a week and oral alogliptin placebo every day,
      whereas patients in the alogliptin group were given oral trelagliptin placebo
      once a week and oral alogliptin every day (double-dummy design). Patients in the
      placebo group were given an oral alogliptin placebo once a day and an oral
      trelagliptin placebo once a week. Our primary outcome was between-groups
      difference in change in HbA1c concentration from baseline to the end of
      treatment. The non-inferiority margin was 0.4%. Our analysis included all
      patients who were randomised and received at least one dose of study drug. The
      study is registered with ClinicalTrials.gov, number NCT01632007. FINDINGS:
      Between May 26, 2012, and Nov 20, 2012, we enrolled 357 patients. 243 patients
      were included in the analysis (101 for trelagliptin, 92 for alogliptin, and 50
      for placebo). In the primary analysis, the least squares mean change in HbA1c
      concentration was -0.33% in the trelagliptin group (SE 0.059) and -0.45% in the
      alogliptin group (0.061) based on the ANCOVA model. The least squares mean
      difference (trelagliptin minus alogliptin) of change from baseline in HbA1c
      concentration was 0.11% (95% CI -0.054 to 0.281). Trelagliptin was non-inferior
      to alogliptin. Both active groups had significantly reduced mean HbA1c
      concentrations at end of treatment compared with placebo (p<0.0001). The
      frequency of adverse events was similar between groups. No hypoglycaemia was
      reported with trelagliptin and the drug was well tolerated. INTERPRETATION: The
      once-weekly DPP-4 inhibitor trelagliptin showed similar efficacy and safety to
      alogliptin once daily in Japanese patients with type 2 diabetes. Trelagliptin
      could be a useful new antidiabetes drug that needs to be given once a week.
      FUNDING: Takeda Pharmaceutical Company.

PMID- 25609194
TI  - Once-weekly DPP-4 inhibitors: do they meet an unmet need?

PMID- 25609195
TI  - Downregulation of EphA5 by promoter methylation in human prostate cancer.
AB  - BACKGROUND: EphA5 is a member of the Eph/ephrin family and plays a critical role
      in the regulation of carcinogenesis. A significant reduction of EphA5 transcripts
      in high-grade prostate cancer tissue was shown using a transcriptomic analysis,
      compared to the low-grade prostate cancer tissue. As less is known about the
      mechanism of EphA5 downregulation and the function of EphA5, here we investigated
      the expression and an epigenetic change of EphA5 in prostate cancer and
      determined if these findings were correlated with clinicopathologic
      characteristics of prostate cancer. METHODS: Seven prostate cell lines (RWPE-1,
      LNCap, LNCap-LN3, CWR22rv-1, PC-3, PC-3M-LN4, and DU145), thirty-nine BPH, twenty
      two primary prostate carcinomas, twenty-three paired noncancerous and cancerous
      prostate tissues were examined via qRT-PCR, methylation-specific PCR, bisulfite
      sequencing, immunohistochemistry and western blotting. The role of EphA5 in
      prostate cancer cell migration and invasion was examined by wound healing and
      transwell assay. RESULTS: Downregulation or loss of EphA5 mRNA or protein
      expression was detected in 28 of 45 (62.2%) prostate carcinomas, 2 of 39 (5.1%)
      hyperplasias, and all 6 prostate cancer cell lines. Methylation of the EphA5
      promoter region was present in 32 of 45 (71.1%) carcinoma samples, 3 of 39 (7.7%)
      hyperplasias, and the 6 prostate cancer cell lines. Among 23 paired prostate
      carcinoma tissues, 16 tumor samples exhibited the hypermethylation of EphA5, and
      15 of these 16 specimens (93.8%) shown the downregulation of EphA5 expression
      than that of their respectively matched noncancerous samples. Immunostaining
      analysis demonstrated that the EphA5 protein was absent or down-regulated in 10
      of 13 (76.9%) available carcinoma samples, and 8 of these 10 samples (80.0%)
      exhibited hypermethylation. The frequency of EphA5 methylation was higher in
      cancer patients with an elevated Gleason score or T3-T4 staging. Following the
      treatment of 6 prostate cancer cell lines with 5-aza-2'-deoxycytidine, the levels
      of EphA5 mRNA were significantly increased. Prostate cancer cells invasion and
      migration were significantly suppressed by ectopic expression of EphA5 in vitro.
      CONCLUSION: Our study provides evidence that EphA5 is a potential target for
      epigenetic silencing in primary prostate cancer and is a potentially valuable
      prognosis predictor and thereapeutic marker for prostate cancer.

PMID- 25609196
TI  - Impact of diabetes on hospital admission and length of stay among a general
      population aged 45 year or more: a record linkage study.
AB  - BACKGROUND: The increased prevalence of diabetes and its significant impact on
      use of health care services, particularly hospitals, is a concern for health
      planners. This paper explores the risk factors for all-cause hospitalisation and
      the excess risk due to diabetes in a large sample of older Australians. METHODS:
      The study population was 263,482 participants in the 45 and Up Study. The data
      assessed were linked records of hospital admissions in the 12 months following
      completion of a baseline questionnaire. All cause and ambulatory care sensitive
      admission rates and length of stay were examined. The associations between
      demographic characteristics, socioeconomic status, lifestyle factors, and health
      and wellbeing and risk of hospitalisation were explored using zero inflated
      Poisson (ZIP) regression models adjusting for age and gender. The ratios of
      adjusted relative rates and 95% confidence intervals were calculated to determine
      the excess risk due to diabetes. RESULTS: Prevalence of diabetes was 9.0% (n =
      23,779). Age adjusted admission rates for all-cause hospitalisation were 631.3
      and 454.8 per 1,000 participant years and the mean length of stay was 8.2 and 7.1
      days respectively for participants with and without diabetes. In people with and
      without diabetes, the risk of hospitalisation was associated with age, gender,
      household income, smoking, BMI, physical activity, and health and wellbeing.
      However, the increased risk of hospitalisation was attenuated for participants
      with diabetes who were older, obese, or had hypertension or hyperlipidaemia and
      enhanced for those participants with diabetes who were male, on low income,
      current smokers or who had anxiety or depression. CONCLUSIONS: This study is one
      of the few studies published to explore the impact of diabetes on hospitalisation
      in a large non-clinical population, the 45 and Up Study. The attenuation of risk
      associated with some factors is likely to be due to correlation between diabetes
      and factors such as age and obesity. The increased risk in association with other
      factors such as gender and low income in participants with diabetes is likely to
      be due to their synergistic influence on health status and the way services are
      accessed.

PMID- 25609197
TI  - The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of
      virus-independent, FGF2-driven tumors.
AB  - The FDA-approved anti-DNA virus agent cidofovir (CDV) is being evaluated in phase
      II/III clinical trials for the treatment of human papillomavirus (HPV)-associated
      tumors. However, previous observations had shown that CDV also inhibits the
      growth of vascular tumors induced by fibroblast growth factor-2 (FGF2)
      transformed FGF2-T-MAE cells. Here, we demonstrate that CDV inhibits metastasis
      induced by FGF2-driven, virus-independent tumor cells. Pre-treatment of
      luciferase-expressing FGF2-T-MAE cells with CDV reduced single cell survival and
      anchorage-independent growth in vitro and lung metastasis formation upon
      intravenous inoculation into SCID mice. This occurred in the absence of any
      effect on homing of FGF2-T-MAE cells to the lungs and on the growth of
      subconfluent cell cultures or subcutaneous tumors in mice. Accordingly, CDV
      protected against lung metastasis when given systemically after tumor cell
      injection. Lung metastases in CDV-treated mice showed reduced Ki67 expression and
      increased nuclear accumulation of p53, indicating that CDV inhibits metastasis by
      affecting single cell survival properties. The anti-metastatic potential of CDV
      was confirmed on B16-F10 melanoma cells, both in zebrafish embryos and mice.
      These findings suggest that CDV may have therapeutic potential as an anti
      metastatic agent and warrants further study to select those tumor types that are
      most likely to benefit from CDV therapy. 

PMID- 25609198
TI  - The soybean-derived peptide lunasin inhibits non-small cell lung cancer cell
      proliferation by suppressing phosphorylation of the retinoblastoma protein.
AB  - Lunasin, a soybean bioactive peptide, has both chemopreventive and
      chemotherapeutic activities. The aim of this study was to determine the
      chemotherapeutic potential of lunasin against human lung cancer. Treatment of non
      small cell lung cancer (NSCLC) cells with highly purified soybean-derived lunasin
      caused limited, cell-line specific anti-proliferative effects on anchorage
      dependent growth whereas two normal bronchial epithelial cell lines were
      unaffected. Lunasin's antiproliferative effects were potentiated upon utilization
      of anchorage-independent conditions. Furthermore, NSCLC cell lines that were
      unaffected by lunasin in anchorage-dependent assays exhibited a dose-dependent
      inhibition in colony formation or colony size. Mouse xenograft studies revealed
      that 30 mg lunasin/kg body weight per day decreased NSCLC H1299 tumor volume by
      63.0% at day 32. Mechanistic studies using cultured NSCLC H661 cells showed that
      lunasin inhibited cell cycle progression at the G1/S phase interface without
      inducing apoptosis. Immunoblot analyses of key cell-cycle proteins demonstrated
      that lunasin altered the expression of the G1 specific cyclin-dependent kinase
      complex components, increased levels of p27Kip1, reduced levels of phosphorylated
      Akt, and ultimately inhibited the sequential phosphorylation of the
      retinoblastoma protein (RB). These results establish for the first time that
      lunasin can inhibit NSCLC proliferation by suppressing cell-cycle dependent
      phosphorylation of RB. 

PMID- 25609199
TI  - Radiotherapy combined with TLR7/8 activation induces strong immune responses
      against gastrointestinal tumors.
AB  - In addition to local cytotoxic activity, radiotherapy may also elicit local and
      systemic antitumor immunity, which may be augmented by immunotherapeutic agents
      including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the
      ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting
      activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined
      treatment induced marked local and systemic responses in subcutaneous and
      orthotopic mouse models of colorectal and pancreatic cancer. In vitro
      cytotoxicity assays as well as in vivo depletion experiments with monoclonal
      antibodies identified NK and CD8 T cells as the cell populations mediating the
      cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic
      cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in
      this setting. The specificity of the immune reaction was confirmed by ELISPOT
      assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy,
      inducing strong local and profound systemic immune responses to tumor antigens
      released by conventional therapy. 

PMID- 25609200
TI  - Increased expression of the immune modulatory molecule PD-L1 (CD274) in
      anaplastic meningioma.
AB  - There are no effective medical treatments for WHO grade III (anaplastic)
      meningioma. Patients with this high-grade malignancy have a median survival of
      less than two years. Therapeutics that modulate the mechanisms that inhibit local
      immune responses in the tumor microenvironment are showing significant and
      durable clinical responses in patients with treatment refractory high-grade
      tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade
      I-III meningiomas using immunohistochemistry and we examined the expression of PD
      L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by
      immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are
      predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the
      number of T cells, including the numbers of CD4+ and CD8+ T cells and cells
      expressing PD-1 and there is also an increase in the number of FOXP3 expressing
      immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic
      meningioma - both mRNA and protein. Using patient derived meningioma cell, we
      confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in
      infiltrating immune cells. This work indicates that high-grade meningioma harbor
      an immunosuppressive tumor microenviroment and that increased Treg cells and
      elevated PD-L1 may contribute to the aggressive phenotype of these tumors. 

PMID- 25609201
TI  - Clusterin facilitates metastasis by EIF3I/Akt/MMP13 signaling in hepatocellular
      carcinoma.
AB  - Clusterin (CLU) is a stress-induced chaperone that confers proliferative and
      survival advantages to cancer cells. However, effects and molecular mechanisms of
      CLU in hepatocellular carcinoma (HCC) metastasis are still unknown. In this
      study, HCC tissue array (n = 198) was utilized to investigate correlation between
      CLU expression and clinicopathological features. Overexpression of CLU in HCC
      tissues was correlated with shorter overall survival and higher tumor recurrence.
      In vitro and in vivo assays demonstrated that silencing CLU attenuated the
      invasion and metastasis of HCC cells, whereas ectopic overexpression of CLU
      resulted in the forced metastasis of HCC cells. We also revealed that CLU
      activated Akt signaling through complexing with eukaryotic translation initiation
      factor 3 subunit I (EIF3I), which in turn promoted matrix metalloproteinase 13
      (MMP13) expression and HCC metastasis. Positive correlations between CLU and
      MMP13, p-Akt, or EIF3I were found in HCC tissues. We further observed that CLU
      knockdown using the CLU inhibitor OGX-011 significantly suppressed HCC metastasis
      in two metastatic models through inhibiting EIF3I/Akt/MMP13 signaling. These
      findings indicate that CLU is an independent predictive factor for prognosis of
      HCC and it facilitates metastasis through EIF3I/Akt/MMP13 signaling. CLU
      suppression using OGX-011 may represent a promising therapeutic option for
      suppressing HCC metastasis. 

PMID- 25609202
TI  - B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non
      small cell lung cancer.
AB  - B7-H1 and B7-H3, two members of the B7 family that are thought to regulate T-cell
      activation, are expressed in human non-small cell lung cancer (NSCLC). However,
      their prognostic significance is poorly understood. In the present study we
      reported that B7-H1 and B7-H3 were expressed in 96/128 (72.7%) and 89/128 (69.5%)
      samples, respectively. B7-H1 and B7-H3 expression and the number of infiltrating
      T-cell intracellular antigen-1+ and interferon-gamma+ cells in NSCLC tissues were
      significantly higher than those in the adjacent tissues (p<0.01). High B7-H1 or
      B7-H3 expression was associated with lymph node metastasis and TNM stage (p<0.05,
      respectively). Sex, TNM stage, B7-H1, B7-H3, and T-cell intracellular antigen-1
      expression remained significant prognostic factors after adjusting for other
      prognostic factors in a multivariate Cox proportional hazards regression model.
      In vitro studies revealed that knockdown of B7-H3 on tumor cells enhanced T-cell
      growth and interferon-gamma secretion when stimulated by anti-CD3 and anti-CD28
      monoclonal antibodies. Interferon-gamma reduced CXCR4 expression on cancer cells
      and inhibited the CXCL12-induced cell migration.B7-H1 and B7-H3 are independent
      predictors of poorer survival in patients with NSCLC. Interference of the signal
      pathways of these negative regulatory molecules might be a new strategy for
      treating NSCLC. 

PMID- 25609203
TI  - Paracrine SDF-1alpha signaling mediates the effects of PSCs on GEM
      chemoresistance through an IL-6 autocrine loop in pancreatic cancer cells.
AB  - Pancreatic cancer exhibits the poorest prognosis among all tumors and is
      characterized by high resistance to the currently available chemotherapeutic
      agents. Our previous studies have suggested that stromal components could promote
      the chemoresistance of pancreatic cancer cells (PCCs). Here, we explored the
      roles of pancreatic stellate cells (PSCs) and the SDF-1alpha/CXCR4 axis in
      pancreatic cancer chemoresitance. Our results showed that primary PSCs typically
      expressed SDF-1alpha, whereas its receptor CXCR4 was highly expressed in PCCs.
      PSC-conditioned medium (PSC-CM) inhibited Gemcitabine (GEM)-induced cytotoxicity
      and apoptosis in the human PCC line Panc-1, which was antagonized by an SDF
      1alpha neutralizing Ab. Recombinant human SDF-1alpha (rhSDF-1alpha) increased IL
      6 expression and secretion in Panc-1 cells in a time and dose-dependent manner,
      and this effect was suppressed by the CXCR4 antagonist AMD3100. rhSDF-1alpha
      protected Panc-1 cells from GEM-induced apoptosis, and the protective effect was
      significantly reduced by blocking IL-6 using a neutralizing antibody. Moreover,
      rhSDF-1alpha increased FAK, ERK1/2, AKT and P38 phosphorylation in Panc-1 cells,
      and either FAK or ERK1/2 inhibition suppressed SDF-1alpha-upregulated IL-6
      expression. SDF-1alpha-induced AKT activation was almost completely blocked by
      FAK inhibition. In conclusion, we demonstrate for the first time that PSCs
      promote the chemoresistance of PCCs to GEM, and this effect is mediated by
      paracrine SDF-1alpha/CXCR4 signaling-induced activation of the intracellular FAK
      AKT and ERK1/2 signaling pathways and a subsequent IL-6 autocrine loop in PCCs.
      Our findings indicate that blocking the PSC-PCC interaction by inhibiting SDF
      1alpha/CXCR4 signaling may be a promising therapeutic strategy for overcoming
      chemoresistance in pancreatic cancer. 

PMID- 25609204
TI  - Set screw fracture with cage dislocation after two-level transforaminal lumbar
      interbody fusion (TLIF): a case report.
AB  - INTRODUCTION: Transforaminal lumbar interbody fusion is a popular procedure used
      to achieve spondylodesis in patients with degenerative lumbar spinal diseases. We
      present a rare case of a patient with a set screw fracture with cage dislocation
      after an open transforaminal lumbar interbody fusion procedure. To the best of
      our knowledge, this case is the first of its kind to be reported. CASE
      PRESENTATION: A 44-year-old Caucasian woman attended a follow-up appointment at
      our hospital 3 months after treatment for second-degree lumbar spondylolisthesis
      (L4/L5) and osteochondrosis (L5/S1) with transforaminal lumbar interbody fusion
      and dorsal spondylodesis. She complained of severe leg pain on the left side. Her
      physical examination revealed a normal neurological status, except for
      paresthesia of the entire left lower limb and at the ball of the left foot.
      Radiological imaging showed breaking of the set screws with cage dislocation.
      Surgical revision was then performed with exchange of the whole dorsal
      instrumentation and the dislocated cage. Six weeks post-operatively, the patient
      was seen again at our clinic without neurological complaints, except for
      decreased sensitivity on the dorsum of her left foot. The wound healing and
      radiological follow-up were uneventful. CONCLUSIONS: Hardware-related
      complications are rarely seen in patients with open transforaminal lumbar
      interbody fusion, but must be kept in mind and can potentially cause severe
      neurological deficits.

PMID- 25609205
TI  - No more top-down reorganisation in mental health but much more funding, experts
      urge.

PMID- 25609206
TI  - Assessment of health service delivery capacities, health providers' knowledge and
      practices related to type 2 diabetes care in Kinshasa primary healthcare network
      facilities, Democratic Republic of the Congo.
AB  - BACKGROUND: Democratic Republic of the Congo (DRC) is experiencing an increase in
      the morbi-mortality related to Non Communicable Diseases (NCD). The reform of DRC
      health system, based on Health District model, is needed in order to tackle this
      public issue. This article used 2006 International Diabetes Federation (IDF)'s
      guidelines to assess the capacities of health facilities belonging to Kinshasa
      Primary Health Care Network (KPHCN) in terms of equipments, as well as the
      knowledge, and the practice of their health providers related to type 2 diabetes
      care. METHODS: A multicentric cross-sectional study was carried in 18 Health
      Facilities (HF) of KPHCN in charge of the follow-up of diabetic patients. The
      presence of IDF recommended materials and equipment was checked and 28 health
      providers were interviewed about their theoretical knowledge about patients'
      management and therapeutic objectives during recommended visits. Chi square test
      or Fisher exact test was used to compare proportions and the Student t-test to
      compare means. RESULTS: The integration of NCD healthcare in the KPHC network is
      feasible. The majority of HF possessed IDF recommended materials except for the
      clinical practice guidelines, urinary test strips, and monofilament, available in
      only one, two and four HF, respectively. KPHCN referral facilities had required
      materials for biochemical analyses, the ECG and for the fundus oculi test.
      Patients' management is characterized by a lack of attention on the impairment of
      renal function during the first visits and a poor respect of recommended
      practices during quarterly and annual visits. A poor knowledge of the reduction
      of cardiovascular risk factors-related therapeutic objectives has been also
      reported. CONCLUSION: The capacities, knowledge, and practice of T2D care were
      poor among HF of KPHCN. The lack of equipment and training of healthcare
      professionals should be supplied even to those who are not medical doctors.
      Special attention must to be put on the clinical practice guidelines formulation
      and sensitization and on supervision.

PMID- 25609207
TI  - Fluoroscopy integrated 3D mapping significantly reduces radiation exposure during
      ablation for a wide spectrum of cardiac arrhythmias.
AB  - AIMS: Despite the use of established 3D-mapping systems, invasive
      electrophysiological studies and catheter ablation require high radiation
      exposure of patients and medical staff. This study investigated whether
      electroanatomic catheter tracking in prerecorded X-ray images on top of an
      existing 3D-mapping system has any impact on radiation exposure. METHODS AND
      RESULTS: Two hundred and ninety-five consecutive patients were either ablated
      with the guidance of the traditional CARTO-3 system (c3) or with help of the
      CARTO-UNIVU system (cU): [typical atrial flutter (AFL) n = 58, drug refractory
      atrial fibrillation (AF) n = 81, ectopic atrial tachycardia (EAT) n = 37,
      accessory pathways (APs) n = 22, symptomatic, idiopathic premature ventricular
      complexes (PVCs) n = 56, ventricular tachycardias (VTs) n = 41]. The CARTO-UNIVU
      allowed a reduction in radiation exposure: fluoroscopy time: AFL c3: 8.6 +/- 0.8
      min vs. cU: 2.9 +/- 0.3 min, P < 0.001; AF c3: 16.0 +/- 1.3 min vs. cU: 6.4 +/-
      0.9 min, P < 0.001; EAT c3: 23.4 +/- 3.1 min vs. cU: 9.7 +/- 1.7 min, P < 0.001;
      AP c3: 7.1 +/- 1.2 min vs. cU: 6.0 +/- 1.5 min, P = 0.59; PVCs c3: 17.6 +/- 2.3
      min vs. cU: 15.2 +/- 2.8 min, P = 0.52; VT c3: 31.4 +/- 3.4 min vs. cU: 17.5 +/-
      2.4 min, P = 0.003. Corresponding to the fluoroscopy time the fluoroscopy dose
      was also reduced significantly. These advantages were not at the cost of
      increased procedure times, periprocedural complications, or decreased acute
      ablation success rates. CONCLUSION: In a wide spectrum of cardiac arrhythmias,
      and especially in AF and VT ablation, fluoroscopy integrated 3D mapping
      contributed to a dramatic reduction in radiation exposure without prolonging
      procedure times and compromising patient's safety. That effect, however, could
      not be maintained in patients with APs and PVCs.

PMID- 25609208
TI  - Irreversible electroporation (IRE) fails to demonstrate efficacy in a prospective
      multicenter phase II trial on lung malignancies: the ALICE trial.
AB  - PURPOSE: To assess safety and efficacy of irreversible electroporation (IRE) of
      lung malignancies. MATERIALS AND METHODS: Patients with primary and secondary
      lung malignancies and preserved lung function were included in this prospective
      single arm trial. Primary and secondary endpoints were safety and efficacy.
      Recruitment goal was 36 subjects in 2 centers. Patients underwent IRE under
      general anesthesia with probe placement performed in Fluoroscopy-CT. The IRE
      system employed was NanoKnife(r) (Angiodynamics). System settings for the
      ablation procedure followed the manufacturer's recommendations. The Mann-Whitney
      U test was used to evaluate the correlation of nine technical parameters with
      local tumor control. Median follow up was 12 months. RESULTS: The expected
      efficacy was not met at interim analysis and the trial was stopped prematurely
      after inclusion of 23 patients (13/10 between both centers). The dominant tumor
      entity was colorectal (n = 13). The median tumor diameter was 16 mm (8-27 mm).
      Pneumothoraces were observed in 11 of 23 patients with chest tubes required in 8
      (35 %). Frequently observed alveolar hemorrhage never led to significant
      hemoptysis. 14/23 showed progressive disease (61 %). Stable disease was found in
      1 (4 %), partial remission in 1 (4 %) and complete remission in 7 (30 %)
      patients. The relative increase of the current during ablation was significantly
      higher in the group treated successfully as compared to the group presenting
      local recurrence (p < 0.05). Needle tract seeding was found in three cases (13
      %). CONCLUSIONS: IRE is not effective for the treatment of lung malignancies. We
      hypothesize that the energy deposition with current IRE probes is highly
      sensitive to air exposure.

PMID- 25609209
TI  - Mapping a Nursing Terminology Subset to openEHR Archetypes. A Case Study of the
      International Classification for Nursing Practice.
AB  - BACKGROUND: Healthcare information technologies have the potential to transform
      nursing care. However, healthcare information systems based on conventional
      software architecture are not semantically interoperable and have high
      maintenance costs. Health informatics standards, such as controlled
      terminologies, have been proposed to improve healthcare information systems, but
      their implementation in conventional software has not been enough to overcome the
      current challenge. Such obstacles could be removed by adopting a multilevel model
      driven approach, such as the openEHR specifications, in nursing information
      systems. OBJECTIVES: To create an openEHR archetype model for the Functional
      Status concepts as published in Nursing Outcome Indicators Catalog of the
      International Classification for Nursing Practice (NOIC-ICNP). METHODS: Four
      methodological steps were followed: 1) extraction of terms from the NOIC-ICNP
      terminology; 2) identification of previously published openEHR archetypes; 3)
      assessment of the adequacy of those openEHR archetypes to represent the terms;
      and 4) development of new openEHR archetypes when required. RESULTS: The "Barthel
      Index" archetype was retrieved and mapped to the 68 NOIC-ICNP Functional Status
      terms. There were 19 exact matches between a term and the correspondent archetype
      node and 23 archetype nodes that matched to one or more NOIC-INCP. No matches
      were found between the archetype and 14 of the NOIC-ICNP terms, and nine
      archetype nodes did not match any of the NOIC-ICNP terms. CONCLUSIONS: The
      openEHR model was sufficient to represent the semantics of the Functional Status
      concept according to the NOIC-ICNP, but there were differences in data
      granularity between the terminology and the archetype, thus producing a
      significantly complex mapping, which could be difficult to implement in real
      healthcare information systems. However, despite the technological complexity,
      the present study demonstrated the feasibility of mapping nursing terminologies
      to openEHR archetypes, which emphasizes the importance of adopting the multilevel
      model-driven approach for the achievement of semantic interoperability between
      healthcare information systems.

PMID- 25609210
TI  - [Bone tumours in lizards and snakes. A rare clinical finding].
AB  - OBJECTIVE: This article presents the pathological findings of 13 bone and
      cartilage tumours in lizards (n=8) and snakes (n=5) within the clinical context.
      MATERIAL AND METHODS: Within a 12-year period (2001-2013), 13 cases of bone
      tumours in reptiles were diagnosed from 358 submitted tumour specimens.
      Pathological examination was performed on eight excisions, two biopsies, two
      amputates and four carcasses. Macroscopically, the samples displayed a light
      coloured surface when cut and had a generally solid consistency. For the
      histological examination, representative specimens were decalcified when
      necessary, embedded in paraffin and stained using haematoxylin and eosin.
      Diagnosis was made based on the World Health Organisation classification for
      veterinary and human medicine. RESULTS: Benign proliferations of the bone
      (ossifying fibroma [n=2], fibrous dysplasia [n=1]) as well as malignant cartilage
      (chondrosarcoma [n=2]) and bone tumours (fibroblastic osteosarcoma [n=2], small
      cell osteosarcoma [n=1]) were found on the head (n=5) and limbs (n=3) of various
      lizard species. In snakes only malignant cartilage neoplasms (chondrosarcoma
      [n=2], dedifferentiated chondrosarcoma [n=3]) of the spine were diagnosed. The
      histological appearance of the malignant tumours ranged from low to highly
      malignant differentiated aggregations of tumour cells, that produced varying
      amounts of osteoid or a hyaline matrix. Curative therapy was achieved in one
      ossifying fibroma by complete surgical removal and in two chondrosarcomas through
      amputation. No metastasis was observed in any of the four necropsies. CONCLUSION
      AND CLINICAL RELEVANCE: Primary neoplasias of the bone are rare tumours in
      reptiles. Considering the information on therapeutic procedures and clinical
      course, the therapy of choice in lizards is complete surgical removal whereas in
      snakes reductive surgery may prolong the survival time.

PMID- 25609211
TI  - Localization Accuracy of Distributed Inverse Solutions for Electric and Magnetic
      Source Imaging of Interictal Epileptic Discharges in Patients with Focal
      Epilepsy.
AB  - Distributed inverse solutions aim to realistically reconstruct the origin of
      interictal epileptic discharges (IEDs) from noninvasively recorded
      electroencephalography (EEG) and magnetoencephalography (MEG) signals. Our aim
      was to compare the performance of different distributed inverse solutions in
      localizing IEDs: coherent maximum entropy on the mean (cMEM), hierarchical
      Bayesian implementations of independent identically distributed sources (IID,
      minimum norm prior) and spatially coherent sources (COH, spatial smoothness
      prior). Source maxima (i.e., the vertex with the maximum source amplitude) of
      IEDs in 14 EEG and 19 MEG studies from 15 patients with focal epilepsy were
      analyzed. We visually compared their concordance with intracranial EEG (iEEG)
      based on 17 cortical regions of interest and their spatial dispersion around
      source maxima. Magnetic source imaging (MSI) maxima from cMEM were most often
      confirmed by iEEG (cMEM: 14/19, COH: 9/19, IID: 8/19 studies). COH electric
      source imaging (ESI) maxima co-localized best with iEEG (cMEM: 8/14, COH: 11/14,
      IID: 10/14 studies). In addition, cMEM was less spatially spread than COH and IID
      for ESI and MSI (p < 0.001 Bonferroni-corrected post hoc t test). Highest
      positive predictive values for cortical regions with IEDs in iEEG could be
      obtained with cMEM for MSI and with COH for ESI. Additional realistic EEG/MEG
      simulations confirmed our findings. Accurate spatially extended sources, as found
      in cMEM (ESI and MSI) and COH (ESI) are desirable for source imaging of IEDs
      because this might influence surgical decision. Our simulations suggest that COH
      and IID overestimate the spatial extent of the generators compared to cMEM. 

PMID- 25609212
TI  - Quantitative Assessment of the Training Improvement in a Motor-Cognitive Task by
      Using EEG, ECG and EOG Signals.
AB  - Generally, the training evaluation methods consist in experts supervision and
      qualitative check of the operator's skills improvement by asking them to perform
      specific tasks and by verifying the final performance. The aim of this work is to
      find out if it is possible to obtain quantitative information about the degree of
      the learning process throughout the training period by analyzing neuro
      physiological signals, such as the electroencephalogram, the electrocardiogram
      and the electrooculogram. In fact, it is well known that such signals correlate
      with a variety of cognitive processes, e.g. attention, information processing,
      and working memory. A group of 10 subjects have been asked to train daily with
      the NASA multi-attribute-task-battery. During such training period the neuro
      physiological, behavioral and subjective data have been collected. In particular,
      the neuro-physiological signals have been recorded on the first (T1), on the
      third (T3) and on the last training day (T5), while the behavioral and subjective
      data have been collected every day. Finally, all these data have been compared
      for a complete overview of the learning process and its relations with the neuro
      physiological parameters. It has been shown how the integration of brain
      activity, in the theta and alpha frequency bands, with the autonomic parameters
      of heart rate and eyeblink rate could be used as metric for the evaluation of the
      learning progress, as well as the final training level reached by the subjects,
      in terms of request of cognitive resources. 

PMID- 25609213
TI  - Amino acid metabolism in intestinal bacteria and its potential implications for
      mammalian reproduction.
AB  - Reproduction is vital for producing offspring and preserving genetic resources.
      However, incidences of many reproductive disorders (e.g. miscarriage,
      intrauterine growth restriction, premature delivery and lower sperm quality) have
      either increased dramatically or remained at high rates over the last decades.
      Mounting evidence shows a strong correlation between enteral protein nutrition
      and reproduction. Besides serving as major nutrients in the diet, amino acids
      (AA) are signaling molecules in the regulation of diverse physiological
      processes, ranging from spermatogenesis to oocyte fertilization and to embryo
      implantation. Notably, the numbers of bacteria in the intestine exceed the
      numbers of host cells by 10 times. Microbes in the small-intestinal lumen
      actively metabolize large amounts of dietary AA and, therefore, affect the entry
      of AA into the portal circulation for whole-body utilization. Changes in the
      composition and abundance of AA-metabolizing bacteria in the gut during
      pregnancy, as well as their translocation to the uterus, may alter uterine
      function and epigenetic modifications of maternal physiology and metabolism,
      which are crucial for pregnancy recognition and fetal development. Thus, the
      presence of the maternal gut microbiota and AA metabolites in the intrauterine
      environments (e.g. endometrium and placenta) and breast milk is likely a unique
      signature for the programming of the whole-body microbiome and metabolism in both
      the fetus and infant. Dietary intervention with functional AA, probiotics and
      prebiotics to alter the abundance and activity of intestinal bacteria may
      ameliorate or prevent the development of metabolic syndrome, while improving
      reproductive performance in both males and females as well as their offspring. 

PMID- 25609215
TI  - Rapid tests for HIV type discrimination in West Africa may perform differently.

PMID- 25609214
TI  - Amphetamine-type stimulants and HIV infection among men who have sex with men:
      implications on HIV research and prevention from a systematic review and meta
      analysis.
AB  - INTRODUCTION: HIV infections and the use of amphetamine-type stimulants (ATS)
      among men who have sex with men (MSM) have been increasing internationally, but
      the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to
      summarize the association between ATS use and HIV infection among MSM. METHODS:
      We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO
      for relevant English, peer-reviewed articles of quantitative studies published
      between 1980 and 25 April 2013. Pooled estimates of the association--prevalence
      rate ratios (PRR, cross-sectional studies), odds ratio (OR, case-control studies)
      and hazard ratio (HR, longitudinal studies), with 95% Confidence Intervals (CI)-
      were calculated using random-effects models stratified by study design and ATS
      group (meth/amphetamines vs. ecstasy). We assessed the existence of publication
      bias in funnel plots and checked for sources of heterogeneity using meta
      regression and subgroup analysis. RESULTS: We identified 6710 article titles,
      screened 1716 abstracts and reviewed 267 full text articles. A total of 35
      publications were eligible for data abstraction and meta-analysis, resulting in
      56 records of ATS use. Most studies (31/35) were conducted in high-income
      countries. Published studies used different research designs, samples and
      measures of ATS use. The pooled association between meth/amphetamine use and HIV
      infection was statistically significant in all three designs (PRR = 1.86; 95% CI:
      1.57-2.17; OR = 2.73; 95% CI: 2.16-3.46 and HR = 3.43; 95% CI: 2.98-3.95,
      respectively, for cross-sectional, case-control and longitudinal studies).
      Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR
      = 1.15; 95% CI: 0.88-1.49; OR = 3.04; 95% CI: 1.29-7.18 and HR = 2.48; 95% CI:
      1.42-4.35, respectively, for cross-sectional, case-control and longitudinal
      studies). RESULTS in cross-sectional studies were highly heterogeneous due to
      issues with ATS measurement and different sampling frames. CONCLUSIONS: While
      meth/amphetamine use was significantly associated with HIV infection among MSM in
      high-income countries in all study designs, evidence of the role of ecstasy in
      HIV infection was lacking in cross-sectional studies. Cross-sectional study
      design, measurement approaches and source populations may also be important
      modifiers of the strength and the direction of associations. Event-specific
      measure of individual drug is required to establish temporal relationship between
      ATS use and HIV infection. HIV prevention programmes targeting MSM should
      consider including interventions designed to address meth/amphetamine use.

PMID- 25609216
TI  - Analyzing large-scale samples confirms the association between rs16892766
      polymorphism and colorectal cancer susceptibility.
AB  - Colorectal cancer (CRC) is a common complex disease caused by the combination of
      genetic variants and environmental factors. Genome-wide association studies
      (GWAS) have been performed and reported some novel CRC susceptibility variants.
      The rs16892766 (8q23.3) polymorphism was first identified to be significantly
      associated with CRC in European ancestry. The following studies investigated this
      association in Chinese, Japanese, Romanian, Swedish, African American, European
      American, and Croatian populations. These studies reported consistent and
      inconsistent results. Here, we reevaluated this association using the relatively
      large-scale samples from 13 studies (N = 59737, 26237 cases and 33500 controls)
      using a meta-analysis by searching the PubMed, Google Scholar and CRCgene
      databases. We observed no significant heterogeneity among the included studies.
      Our results showed significant association between rs16892766 polymorphism and
      CRC (P = 1.33E-35, OR = 1.23, 95% CI 1.20-1.27). Collectively, our analysis
      further supports previous findings that the rs16892766 polymorphism is
      significantly associated with CRC susceptibility. We believe that our findings
      will be very useful for future genetic studies on CRC. 

PMID- 25609217
TI  - Ferroelectrically driven spatial carrier density modulation in graphene.
AB  - The next technological leap forward will be enabled by new materials and
      inventive means of manipulating them. Among the array of candidate materials,
      graphene has garnered much attention; however, due to the absence of a
      semiconducting gap, the realization of graphene-based devices often requires
      complex processing and design. Spatially controlled local potentials, for
      example, achieved through lithographically defined split-gate configurations,
      present a possible route to take advantage of this exciting two-dimensional
      material. Here we demonstrate carrier density modulation in graphene through
      coupling to an adjacent ferroelectric polarization to create spatially defined
      potential steps at 180 degrees -domain walls rather than fabrication of local
      gate electrodes. Periodic arrays of p-i junctions are demonstrated in air (gate
      tunable to p-n junctions) and density functional theory reveals that the origin
      of the potential steps is a complex interplay between polarization, chemistry,
      and defect structures in the graphene/ferroelectric couple. 

PMID- 25609218
TI  - Cold snare polypectomy with pull technique of flat colonic polyps up to 12 mm: a
      porcine model.
AB  - BACKGROUND: Most colonoscopic complications are polypectomy-related and occur
      more frequently during the removal of numerous small polyps. Therefore, it is
      important to have the best polypectomy approach of small polyps. The aim of the
      present animal study was to investigate the effectiveness and safety of cold
      snare polypectomy (CSP) technique combined with light pull of the snare in order
      to peel the mucosal and upper submucosal layer, namely pull CSP (PCSP), for the
      removal of polyps sized up to 12 mm in porcine models. METHODS: We performed a
      series of polypectomies in the pig colon with a double-channel experimental
      gastroscope using PCSP technique. RESULTS: Thirty cases of "polyps" larger than 7
      mm and up to 12 mm were treated using PCSP technique. No sign of perforation or
      bleeding was observed in all cases performed with PCSP. CONCLUSIONS: According to
      our preliminary results in this animal model, PCSP could be a safe and effective
      technique for flat colonic polyp removal up to 12 mm in size consistent with the
      basic polypectomy principles.

PMID- 25609219
TI  - Physiologically based pharmacokinetic modeling for sequential metabolism: effect
      of CYP2C19 genetic polymorphism on clopidogrel and clopidogrel active metabolite
      pharmacokinetics.
AB  - Clopidogrel is a prodrug that needs to be converted to its active metabolite
      (clopi-H4) in two sequential cytochrome P450 (P450)-dependent steps. In the
      present study, a dynamic physiologically based pharmacokinetic (PBPK) model was
      developed in Simcyp for clopidogrel and clopi-H4 using a specific sequential
      metabolite module in four populations with phenotypically different CYP2C19
      activity (poor, intermediate, extensive, and ultrarapid metabolizers) receiving a
      loading dose of 300 mg followed by a maintenance dose of 75 mg. This model was
      validated using several approaches. First, a comparison of predicted-to-observed
      area under the curve (AUC)0-24 obtained from a randomized crossover study
      conducted in four balanced CYP2C19-phenotype metabolizer groups was performed
      using a visual predictive check method. Second, the interindividual and
      intertrial variability (on the basis of AUC0-24 comparisons) between the
      predicted trials and the observed trial of individuals, for each phenotypic
      group, were compared. Finally, a further validation, on the basis of drug-drug
      interaction prediction, was performed by comparing observed values of clopidogrel
      and clopi-H4 with or without dronedarone (moderate CYP3A4 inhibitor)
      coadministration using a previously developed and validated physiologically based
      PBPK dronedarone model. The PBPK model was well validated for both clopidogrel
      and its active metabolite clopi-H4, in each CYP2C19-phenotypic group, whatever
      the treatment period (300-mg loading dose and 75-mg last maintenance dose). This
      is the first study proposing a full dynamic PBPK model able to accurately predict
      simultaneously the pharmacokinetics of the parent drug and of its primary and
      secondary metabolites in populations with genetically different activity for a
      metabolizing enzyme. 

PMID- 25609220
TI  - Hydrastine pharmacokinetics and metabolism after a single oral dose of goldenseal
      (Hydrastis canadensis) to humans.
AB  - The disposition and metabolism of hydrastine was investigated in 11 healthy
      subjects following an oral dose of 2.7 g of goldenseal supplement containing 78
      mg of hydrastine. Serial blood samples were collected for 48 hours, and urine was
      collected for 24 hours. Hydrastine serum and urine concentrations were determined
      by Liquid Chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic
      parameters for hydrastine were calculated using noncompartmental methods. The
      maximal serum concentration (Cmax) was 225 +/- 100 ng/ml, Tmax was 1.5 +/- 0.3
      hours, and area under the curve was 6.4 +/- 4.1 ng ? h/ml ? kg. The elimination
      half-life was 4.8 +/- 1.4 hours. Metabolites of hydrastine were identified in
      serum and urine by using liquid chromatography coupled to high-resolution mass
      spectrometry. Hydrastine metabolites were identified by various mass
      spectrometric techniques, such as accurate mass measurement, neutral loss
      scanning, and product ion scanning using Quadrupole-Time of Flight (Q-ToF) and
      triple quadrupole instruments. The identity of phase II metabolites was further
      confirmed by hydrolysis of glucuronide and sulfate conjugates using bovine beta
      glucuronidase and a Helix pomatia sulfatase/glucuronidase enzyme preparation.
      Hydrastine was found to undergo rapid and extensive phase I and phase II
      metabolism. Reduction, O-demethylation, N-demethylation, hydroxylation,
      aromatization, lactone hydrolysis, and dehydrogenation of the alcohol group
      formed by lactone hydrolysis to the ketone group were observed during phase I
      biotransformation of hydrastine. Phase II metabolites were primarily glucuronide
      and sulfate conjugates. Hydrastine undergoes extensive biotransformation, and
      some metabolites may have pharmacological activity. Further study is needed in
      this area.

PMID- 25609221
TI  - Testing measurement invariance of the GHQ-28 in stroke patients.
AB  - BACKGROUND: In order to combine self-reported measures data from multiple studies
      to conduct an integrated data analysis, the construct measured must have the same
      meaning across the studies. This study investigated the measurement invariance of
      the General Health questionnaire (GHQ-28) in two stroke studies before combining
      the data for an integrative data analysis. METHODS: The study used data from the
      Stroke Outcomes Study 1 (SOS1, n = 448) and second Stroke Outcomes Study (SOS2, n
      = 585). The initial analysis was a confirmatory factor analysis (CFA) for each
      study separately to confirm the four-factor structure of GHQ-28 questionnaire.
      Multi-group confirmatory factor analysis (MG-CFA) was used to assess the
      measurement invariance of the GHQ-28 questionnaire in the two stroke cohorts.
      Measurement invariance at configural invariance (same items associated with same
      factor across groups); factor loading invariance (equal factor loadings across
      groups) and scalar invariance (equal intercepts across groups) was examined.
      RESULTS: CFA supported all three invariances measured. CONCLUSION: Results showed
      that the GHQ-28 questionnaire has comparable measurement properties in the SOS1
      and SOS2 stroke studies. Strong measurement invariance was established, and based
      on the results from this study, integrative data analysis of GHQ-28 scores from
      the two stroke studies is merited.

PMID- 25609222
TI  - Chest-abdomen-pelvis CT for staging in cancer patients: dose effectiveness and
      image quality using automated attenuation-based tube potential selection.
AB  - BACKGROUND: Evaluation of automated attenuation-based tube potential selection
      and its impact on image quality and radiation dose in CT (computed tomography)
      examinations for cancer staging. METHODS: A total of 110 (59 men, 51 women)
      patients underwent chest-abdomen-pelvis CT examinations; 55 using a fixed tube
      potential of 120 kV/current of 210 Reference mAs (using CareDose4D), and 55 using
      automated attenuation-based tube potential selection (CAREkV) also using a
      current of 210 Reference mAs. RESULTS: Diagnostic image quality was obtained from
      all patients. The median DLP (703.5 mGy . cm, range 390-2203 mGy . cm) was 7.9%
      lower when using the algorithm compared with the standard 120 kV protocol (median
      756 mGy . cm, range 345-2267 mGy . cm). A reduction in potential to 100 kV
      occurred in 32 cases; therefore, these patients received significantly lower
      radiation exposure compared with the 120 kV protocol. CONCLUSION: Automated
      attenuation-based tube potential selection produces good diagnostic image quality
      in chest-abdomen-pelvis CT and reduces the patient's overall radiation dose by
      7.9% compared to the standard 120 kV protocol.

PMID- 25609223
TI  - Demonstrating comparative in vitro bioequivalence for animal drug products
      through chemistry and manufacturing controls and physicochemical
      characterization: a proposal.
AB  - The assessment of in vivo bioequivalence (BE) of nonsystemically absorbed drug
      products has been a longstanding challenge facing drug manufacturers and
      regulators of human or animal health products. Typically, in situations where
      blood level BE studies are not feasible, clinical endpoint BE trials have
      provided the only option for generating interproduct comparisons. Given the
      imprecision and logistic challenges associated with these studies, there has been
      an effort to identify alternative pathways that can reliably ensure the
      equivalence of product performance and quality. This commentary provides a
      proposal for an in vitro approach for evaluating the in vivo BE of veterinary
      drug products that are either nonsystemically absorbed or that act both locally
      and systemically but where the local site of action is proximal to the absorption
      window. The assumption underlying this approach is that equivalence in product
      physicochemical attributes and in vitro product performance translates to
      equivalence in product in vivo behavior. For sponsors with a right of reference
      to underlying safety and effectiveness data, this approach could be used to
      support pre and post-approval changes. When comparing a generic test product to
      the pioneer (reference listed new animal drug, RLNAD) product, a demonstration of
      sameness across a battery of in vitro test procedures could be used to confirm
      that the test and RLNAD products are bioequivalent. 

PMID- 25609224
TI  - A hybrid Markov chain-von Mises density model for the drug-dosing interval and
      drug holiday distributions.
AB  - Lack of adherence is a frequent cause of hospitalizations, but its effects on
      dosing patterns have not been extensively investigated. The purpose of this work
      was to critically evaluate a novel pharmacometric model for deriving the
      relationships of adherence to dosing patterns and the dosing interval
      distribution. The hybrid, stochastic model combines a Markov chain process with
      the von Mises distribution. The model was challenged with electronic medication
      monitoring data from 207 hypertension patients and against 5-year persistence
      data. The model estimates distributions of dosing runs, drug holidays, and dosing
      intervals. Drug holidays, which can vary between individuals with the same
      adherence, were characterized by the patient cooperativity index parameter. The
      drug holiday and dosing run distributions deviate markedly from normality. The
      dosing interval distribution exhibits complex patterns of multimodality and can
      be long-tailed. Dosing patterns are an important but under recognized covariate
      for explaining within-individual variance in drug concentrations. 

PMID- 25609225
TI  - Climate variation explains a third of global crop yield variability.
AB  - Many studies have examined the role of mean climate change in agriculture, but an
      understanding of the influence of inter-annual climate variations on crop yields
      in different regions remains elusive. We use detailed crop statistics time series
      for ~13,500 political units to examine how recent climate variability led to
      variations in maize, rice, wheat and soybean crop yields worldwide. While some
      areas show no significant influence of climate variability, in substantial areas
      of the global breadbaskets, >60% of the yield variability can be explained by
      climate variability. Globally, climate variability accounts for roughly a third
      (~32-39%) of the observed yield variability. Our study uniquely illustrates
      spatial patterns in the relationship between climate variability and crop yield
      variability, highlighting where variations in temperature, precipitation or their
      interaction explain yield variability. We discuss key drivers for the observed
      variations to target further research and policy interventions geared towards
      buffering future crop production from climate variability. 

PMID- 25609226
TI  - Formylated chloro-bridged iridium(III) dimers as OLED materials: opening up new
      possibilities.
AB  - In this study, a series of four formyl-substituted chloro-bridged iridium(iii)
      dimers were prepared. Their absorption, photophysical and electrochemical
      properties were studied in dichloromethane solution. It was found that as the
      formyl content increased on the cyclometalating ligands, emission unexpectedly
      became brighter. Organic light-emitting diodes (OLEDs) were fabricated using each
      of these iridium dimers as the emitter. The OLED fabricated using the brightest
      of the series, 2b, as the dopant afforded a decent external quantum efficiency
      (EQE) of 2.6%. This suggests that chloro-bridged iridium dimers are potential
      candidates as solid-state emitters.

PMID- 25609227
TI  - Vascular age to determine cardiovascular disease risk: A systematic review of its
      concepts, definitions, and clinical applications.
AB  - BACKGROUND: Vascular age is an alternate means of representing an individual's
      cardiovascular risk. Little consensus exists on what vascular age represents and
      its clinical utility has not been determined. We systematically reviewed the
      literature to provide a comprehensive overview of different methods that have
      been used to define vascular age, and to examine its potential clinical value in
      patient communication and risk prediction. DESIGN: This was a systematic review
      with data sources of PubMed and Embase. RESULTS: We identified 39 articles on
      vascular age, 20 proposed to use vascular age as a communication tool and 19
      proposed to use vascular age as a means to improve cardiovascular risk
      prediction. Eight papers were methodological and 31 papers reported on vascular
      age in study populations. Of these 31 papers, vascular age was a direct
      translation of the absolute risk estimated by existing cardiovascular risk
      prediction models in 15 papers, 12 derived vascular age from the reference values
      of an additional test, and in three papers vascular age was defined as the age at
      which the estimated cardiovascular risk equals the risk from non-invasive imaging
      observed degree of atherosclerosis. One trial found a small effect on risk factor
      levels when vascular age was communicated instead of cardiovascular risk.
      CONCLUSION: Despite sharing a common name, various studies have proposed distinct
      ways to define and measure vascular age. Studies into the effects of vascular age
      as a tool to improve cardiovascular risk prediction or patient communication are
      scarce but will be required before its clinical use can be justified.

PMID- 25609228
TI  - Dynamic membrane behaviours during constant flux filtration in membrane
      bioreactor coupled with mesh filter.
AB  - This study investigated the long-term filtration of mesh filter with the formed
      dynamic membrane in bioreactor. The trend of transmembrane pressure (TMP)
      variations highly corresponded to the thickness and compactness index of dynamic
      membrane. The dynamic membrane was fractionated by applying two cleaning
      protocols, that is, rinsing and chemical cleaning. The desorbed fraction,
      consisting of soluble microbial products (>70%), provided a stickiness surface
      for formation of consecutive biomass layer which featured a high concentration of
      extracellular polymeric substances (>75%). The chemical oxygen demand (COD)
      removal was 70%, 89%, and 92% for period of 0-26, 26-49, and 49-67 day,
      respectively, which indicated that further development of dynamic membrane
      increased the TMP without improvement in the effluent quality (TMP: 50-200 mbar,
      COD removal: 89%; TMP: 200-600 mbar, COD removal: 92%). The average NH4+-N and TN
      removal was about 76% and 21%, respectively. The effluent turbidity fell less
      than 2 NTU after 26 days of filtration.

PMID- 25609230
TI  - Characterization of the colistin (polymyxin E1 and E2) biosynthetic gene cluster.
AB  - Colistin is a mixture of polymyxin E1 and E2, bactericidal pentacationic
      lipopeptides used to treat infections caused by Gram-negative pathogens such as
      Pseudomonas aeruginosa and Klebsiella pneumoniae. Industrial production of
      colistin is obtained by a fermentation process of the natural producer
      Paenibacillus polymyxa var colistinus. NonRibosomal peptide synthetases (NRPS)
      coding the biosynthesis of polymyxins A, B and P have been recently described,
      rendering thereof the improvement of their production possible. However, the
      colistin biosynthesis pathway was not published so far. In this study, a
      Paenibacillus alvei has been identified by biochemical (Api 50 CH system) and
      molecular (16S rDNA sequencing) methods. Its culture supernatant displayed
      inhibitory activity against Gram-negative bacteria (P. aeruginosa, K. pneumoniae,
      Salmonella spp.). Two polymyxins, E1 and E2, were recovered from the supernatant
      and were characterized by high resolution LC-MS. A genomic library (960 clones)
      was constructed to identify the gene cluster responsible for biosynthesis of
      polymyxins. Selection of the clones harbouring the sequences of interest was
      obtained by a simple PCR-based screening. We used primers targeting NRPS
      sequences leading to the incorporation of amino acids present in polymyxins E.
      The sequences from three clones of interest were assembled on 50.4 kb. Thus, five
      open reading frames corresponding to a new NRPS gene cluster of 41 kb were
      identified. In silico, analyses revealed the presence of three NRPS implicated in
      the biosynthesis of polymyxins E. This work provides insightful information on
      colistin biosynthesis and might contribute to future drug developments in this
      group of antibiotics. 

PMID- 25609231
TI  - Recommended dairy product intake modulates circulating fatty acid profile in
      healthy adults: a multi-centre cross-over study.
AB  - Dairy products are rich sources of an array of fatty acids (FA) that have been
      shown individually and in certain clusters to exert varying effects on
      cardiovascular health, for which the circulating lipid profile is a powerful
      biomarker. Whether the profile of these FA is reflected in blood upon short terms
      of intake, possibly contributing to the lipid-related health impacts of dairy
      products, remains to be fully established. The objectives of the present study
      were to assess a recommended dairy product consumption in relation to circulating
      FA and lipid profiles, and to evaluate certain FA in dairy fat as potential
      biomarkers of intake. In a free-living, multi-centre, cross-over design, 124
      healthy individuals consumed 3 servings/d of commercial dairy (DAIRY; 1% fat
      milk, 1.5% fat yogurt and 34% fat cheese) or energy-equivalent control (CONTROL;
      fruit and vegetable juice, cashews and a cookie) products for 4 weeks each,
      separated by a 4-week washout period. Plasma FA and serum lipid profiles were
      assessed by standard methods at the end of each dietary phase. After 4 weeks of
      intake, plasma levels of FA pentadecanoic acid (15 : 0) and heptadecanoic acid
      (17 : 0) were higher (0.26 v. 0.22% and 0.42 v. 0.39% of the total identified FA,
      respectively) after the DAIRY phase than after the CONTROL phase (P< 0.0001).
      This was accompanied by a small but significant increase in serum LDL-cholesterol
      levels after the DAIRY phase compared with the CONTROL phase (+0.08 mmol/l; P=
      0.04). In conclusion, intake of 3 servings/d of conventional dairy products may
      modify certain circulating FA and lipid profiles within 4 weeks, where 15 : 0 and
      17 : 0 may be potential short-term biomarkers of intake.

PMID- 25609229
TI  - How to constrain and maintain a lexicon for the treatment of progressive semantic
      naming deficits: Principles of item selection for formal semantic therapy.
AB  - The progressive degradation of semantic memory is a common feature of many forms
      of dementia, including Alzheimer's disease and the semantic variant of primary
      progressive aphasia (svPPA). One of the most functionally debilitating effects of
      this semantic impairment is the inability to name common people and objects
      (i.e., anomia). Clinical management of a progressive, semantically based anomia
      presents extraordinary challenges for neurorehabilitation. Techniques such as
      errorless learning and spaced-retrieval training show promise for retraining
      forgotten words. However, we lack complementary detail about what to train (i.e.,
      item selection) and how to flexibly adapt the training to a declining cognitive
      system. This position paper weighs the relative merits of several treatment
      rationales (e.g., restore vs. compensate) and advocates for maintenance of known
      words over reacquisition of forgotten knowledge in the context of semantic
      treatment paradigms. I propose a system for generating an item pool and outline a
      set of core principles for training and sustaining a micro-lexicon consisting of
      approximately 100 words. These principles are informed by lessons learned over
      the course of a Phase I treatment study targeting language maintenance over a 5
      year span in Alzheimer's disease and SvPPA. Finally, I propose a semantic
      training approach that capitalises on lexical frequency and repeated training on
      conceptual structure to offset the loss of key vocabulary as disease severity
      worsens. 

PMID- 25609232
TI  - Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma:
      implication of targets FN1 and TJP1 in metastasis.
AB  - BACKGROUND: Transcription factor CP2 (TFCP2) is overexpressed in hepatocellular
      carcinoma(HCC) and correlated with the progression of the disease. Here we report
      the use of an integrated systems biology approach to identify genome-wide scale
      map of TFCP2 targets as well as the molecular function and pathways regulated by
      TFCP2 in HCC. METHODS: We combined Chromatin immunoprecipitation (ChIP) on chip
      along with gene expression microarrays to study global transcriptional regulation
      of TFCP2 in HCC. The biological functions, molecular pathways, and networks
      associated with TFCP2 were identified using computational approaches. Validation
      of selected target gene expression and direct binding of TFCP2 to promoters were
      performed by ChIP -PCR and promoter reporter. RESULTS: TFCP2 fostered a highly
      aggressive and metastatic phenotype in different HCC cells. Transcriptome
      analysis showed that alteration of TFCP2 in HCC cells led to change of genes in
      biological functions involved in cancer, cellular growth and proliferation,
      angiogenesis, cell movement and attachment. Pathways related to cell movement and
      cancer progression were also enriched. A quest for TFCP2-regulated factors
      contributing to metastasis, by integration of transcriptome and ChIP on chip
      assay, identified fibronectin 1 (FN1) and tight junction protein 1 (TJP1) as
      targets of TFCP2, and as key mediators of HCC metastasis. Promoter reporter
      identified the TFCP2-responsive region, and located the motifs of TFCP2-binding
      sites in the FN1 promoter, which then was confirmed by ChIP-PCR. We further
      showed that FN1 inhibition blocks the TFCP2-induced increase in HCC cell
      aggression, and that overexpression of TFCP2 can rescue the effects of FN1
      inhibition. Knock down of TJP1 could also rescue, at least in part, the
      aggressive effect of TFCP2 knockdown in HCC cells. CONCLUSIONS: The
      identification of global targets, molecular pathways and networks associated with
      TFCP2, together with the discovery of the effect of TFCP2 on FN1 and TJP1 that
      are involved in metastasis, adds to our understanding of the mechanisms that
      determine a highly aggressive and metastatic phenotype in hepatocarcinogenesis.

PMID- 25609233
TI  - Palliative care and the aggressiveness of end-of-life care in patients with
      advanced pancreatic cancer.
AB  - BACKGROUND: We examined the impact of palliative care (PC) on aggressiveness of
      end-of-life care for patients with advanced pancreatic cancer. Measures of
      aggressive care included chemotherapy within 14 days of death; and at least one
      intensive care unit (ICU) admission, more than one emergency department (ED)
      visit, and more than one hospitalization, all within 30 days of death. METHODS: A
      retrospective population-based cohort study using administrative data was
      conducted in patients with advanced pancreatic cancer from 2005 to 2010 in
      Ontario, Canada. Multivariable logistic regression was performed with the above
      measures of aggressive care as the outcomes of interest and PC as the main
      exposure, adjusting for covariables. Secondary analyses examined intensity of PC
      as the main exposure defined in two ways: 1) absolute number of PC visits before
      the outcome of interest (0, 1, 2, 3+ visits) and 2) monthly rate of PC visits.
      RESULTS: The cohort included 5381 patients (median survival 75 days); 2816
      (52.3%) had received a PC consultation. PC consultation was associated with
      decreased use of chemotherapy near death (odds ratio [OR] = 0.34, 95% confidence
      interval [CI] = 0.25 to 0.46); lower risk of ICU admission: OR = 0.12, 95% CI =
      0.08 to 0.18; multiple ED visits: OR = 0.19, 95% CI = 0.16 to 0.23; multiple
      hospitalizations near death: OR = 0.24, 95% CI = 0.19 to 0.31). A per-unit
      increase in the monthly rate of PC visits was associated with lower odds of
      aggressive care for all four outcomes. CONCLUSION: PC consultation and a higher
      intensity of PC were associated with less aggressive care near death in patients
      with advanced pancreatic cancer.

PMID- 25609234
TI  - Survival in elderly men in relation to midlife and current BMI.
AB  - BACKGROUND: the relationship between BMI and mortality is U-shaped in the elderly
      but may be modified by midlife BMI and change in weight. OBJECTIVE: to elucidate
      mortality prediction by BMI trajectory in older men. SUBJECTS: the Oslo cohort of
      men born in 1923-32 were screened for BMI and cardiovascular risk in 1972-73.
      Survivors were rescreened at ages of 68-77 years, and all-cause mortality was
      followed from 2000 to 2011. METHODS: we calculated Cox regression proportional
      hazards for 11-year mortality rates in relation to BMI change among 5,240 men
      with no reported disease in 1972-73 and complete data. Models were adjusted for
      demographics, medications and disease. Men with BMI < 25 kg/m(2) in midlife (1972
      73) and in 2000 were the reference group. RESULTS: men whose BMI changed from <25
      kg/m(2) in midlife to 25-29.9 kg/m(2) in 2000 carried the lowest mortality risk
      (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94). Men with BMI >=
      30 kg/m(2) in midlife were at highest risk (HR 1.79; 95% CI 1.12-2.88 if
      reclassified to 25-29.9 kg/m(2) in 2000 and HR 1.39; 95% CI 1.05-1.85 if BMI
      remained >=30 kg/m(2) in 2000). Men with BMI 25-29.9 kg/m(2) in midlife that
      reclassified to <25 kg/m(2) in 2000 had increased risk. Findings were similar
      when percentage change in BMI was the outcome. CONCLUSION: survival in older men
      with normal weight at midlife was associated with BMI gain after midlife while
      midlife obesity increased risk regardless of subsequent change.

PMID- 25609235
TI  - Autophagy enhances NFkappaB activity in specific tissue macrophages by
      sequestering A20 to boost antifungal immunity.
AB  - Immune responses must be well restrained in a steady state to avoid excessive
      inflammation. However, such restraints are quickly removed to exert antimicrobial
      responses. Here we report a role of autophagy in an early host antifungal
      response by enhancing NFkappaB activity through A20 sequestration. Enhancement of
      NFkappaB activation is achieved by autophagic depletion of A20, an NFkappaB
      inhibitor, in F4/80(hi) macrophages in the spleen, peritoneum and kidney. We show
      that p62, an autophagic adaptor protein, captures A20 to sequester it in the
      autophagosome. This allows the macrophages to release chemokines to recruit
      neutrophils. Indeed, mice lacking autophagy in myeloid cells show higher
      susceptibility to Candida albicans infection due to impairment in neutrophil
      recruitment. Thus, at least in the specific aforementioned tissues, autophagy
      appears to break A20-dependent suppression in F4/80(hi) macrophages, which
      express abundant A20 and contribute to the initiation of efficient innate immune
      responses. 

PMID- 25609238
TI  - MicroRNA-429 functions as a regulator of epithelial-mesenchymal transition by
      targeting Pcdh8 during murine embryo implantation.
AB  - STUDY QUESTION: What is the role of miR-429 in murine embryo implantation?
      SUMMARY ANSWER: miR-429 functions as a suppressor of epithelial-mesenchymal
      transition (EMT) during the process of embryo implantation by reverse regulation
      of Pcdh8. WHAT IS KNOWN ALREADY: MicroRNAs (miRNAs) may serve as promising
      regulators of embryo implantation. miR-429 was recently found to be down
      regulated during embryo implantation period in a microarray analysis. STUDY
      DESIGN, SIZE, DURATION: The expression profile of miR-429 was clarified in a
      series of models, and the target gene was confirmed. The in vivo and in vitro
      effect of miR-429 on embryo implantation was examined. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Pregnancy was produced by natural mating between female
      C57BL6/J mice and male mice, and a series of models, including pseudopregnancy,
      delayed implantation and artificial decidualization, were established. The
      expression profile of miR-429 during the embryo implantation period was clarified
      in these models. Candidate target genes of miR-429 were predicted by
      bioinformatic analysis and tested by luciferase activity assay. The in vivo
      effects of miR-429 on embryo implantation were also examined. The in vitro
      effects of miR-429 on EMT were studied by examining migratory and invasive
      capacities by transwell assay and expression profiles of cadherin family members
      by western blotting and qRT-PCR. MAIN RESULTS AND THE ROLE OF CHANCE: The
      expression profile of miR-429 in animal models suggested its down-regulation
      should be dependent on the presence and status of blastocysts and on endometrial
      decidualization. The luciferase activity assay showed that Pcdh8, a member of
      cadherin gene family, was the target gene of miR-429, and miR-429 suppressed the
      expression of Pcdh8 mRNA and protein. Gain-of-function of miR-429 in vivo
      resulted in a significant reduction of the number of implantation sites, but had
      little effect on fertilization. Up-regulation of miR-429 in vitro led to
      suppression of mesenchymal marker genes Vim, Cdh2, Zeb1 and Zeb2, and activation
      of epithelial marker gene Cdh1, resulting in suppression of the migratory and
      invasive capacities of cells. miR-429 also partially abrogated TGF-beta-induced
      EMT. The dysregulated expression profiles of EMT markers during embryo
      implantation period could be partially reversed by gain-of-function of miR-429 in
      vivo. LIMITATIONS, REASONS FOR CAUTION: The association of miR-429 with other
      members of the miR-200 family in embryo implantation remains to be determined.
      The relationship between miR-429 and the cadherin family needs more intensive
      description and the detailed mechanism of miR-429 in regulating the cadherin
      family needs to be elucidated. WIDER IMPLICATIONS OF THE FINDINGS: Our findings
      indicate that miR-429 plays a major role in embryo implantation as a suppressor
      of EMT by targeting Pcdh8. This information could contribute to a better
      understanding of the mechanisms involved in the miRNA-mediated regulation of
      embryo implantation, and subsequently improve treatments for infertility. The
      findings are consistent with that from previous research of the other members in
      miR-200 family in embryo implantation and in the EMT. STUDY FUNDING/COMPETING
      INTERESTS: This study was supported by the Natural Science Foundation of China
      (Grant number: 81170592), and Special Fund from National Excellent Doctoral
      Dissertation (Grant number: 201079). There was no conflict of interest.

PMID- 25609236
TI  - Healthy control subjects are poorly defined in case-control studies of irritable
      bowel syndrome.
AB  - BACKGROUND: Case-control studies are vital for understanding the pathophysiology
      of gastrointestinal disease. While the definition of disease is clear, the
      definition of healthy control is not. This is particularly relevant for
      functional bowel diseases such as irritable bowel syndrome (IBS). In this study,
      a systematic review formed the basis for a prospective study evaluating the
      effectiveness of commonly used techniques for defining healthy controls in IBS.
      METHODS: A systematic review of the literature was conducted to identify case
      control studies involving functional gastrointestinal disorders. "Lack of Rome
      criteria", self-description as "healthy" and the bowel disease questionnaire
      (BDQ) were common methods for identifying healthy controls. These 3 methods were
      then applied to a cohort of 53 non-patient subjects to determine their validity
      compared to objective outcome measures (7-day stool diary). RESULTS: "Lack of
      Rome criteria" and "healthy" self-description were the most common methods for
      identifying healthy control subjects, but many studies failed to describe the
      methods used. In the prospective study, more subjects were identified as non
      healthy using the BDQ than using either lack of Rome criteria (P=0.01) or
      "healthy" self-description (P=0.026). Furthermore, stool diaries identified
      several subjects with abnormal stool form and/or frequency which were not
      identified using lack of Rome criteria or the "healthy" question. Comparisons
      revealed no agreement (kappa) between the different methods for defining healthy
      controls. CONCLUSIONS: The definitions of healthy controls in studies of
      functional bowel diseases such as IBS are inconsistent. Since functional symptoms
      are common, a strict definition of "normal" is needed in this area of research.

PMID- 25609239
TI  - Behavioral mechanism of human sperm in thermotaxis: a role for hyperactivation.
AB  - STUDY QUESTION: What is the behavioral mechanism underlying the response of human
      spermatozoa to a temperature gradient in thermotaxis? SUMMARY ANSWER: Human
      spermatozoa swim up a temperature gradient by modulating their speed and
      frequencies of hyperactivation events and turns. WHAT IS KNOWN ALREADY:
      Capacitated human spermatozoa are capable of thermotactically responding to a
      temperature gradient with an outcome of swimming up the gradient. This response
      occurs even when the gradient is very shallow. STUDY DESIGN, SIZE, DURATION:
      Human sperm samples were exposed to a fast temperature change. A quantitative
      analysis of sperm motility parameters, flagellar wave propagation, and
      directional changes before, during, and after the temperature change was carried
      out. PARTICIPANTS/MATERIALS, SETTING, METHODS: The swimming behavior of 44 human
      sperm samples from nine healthy donors was recorded under a phase-contrast
      microscope at 75 and 2000 frames/s. A temperature shift was achieved by using a
      thermoregulated microscope stage. The tracks made by the cells were analyzed by a
      homemade computerized motion analysis system and ImageJ software. MAIN RESULTS
      AND THE ROLE OF CHANCE: A temperature shift from 31 to 37 degrees C resulted in
      enhanced speed and a lower frequency of turning events. These were reflected in a
      35 +/- 1% (mean +/- SEM) increase of the straight-line velocity, 33 +/- 1%
      increase of the average path velocity, 11 +/- 1% increase of the curvilinear
      velocity, 20 +/- 1% increase of the wobble, and 4 +/- 1% increase of the
      linearity. Qualitatively, the inverse trend was observed in response to a 37-to
      31 degrees C shift. In addition, the amplitude of flagellar waves increased close
      to the sperm head, resulting in higher side-to-side motion of the head and,
      often, hyperactivation. This increase in the extent of sperm hyperactivation was
      reflected in an increase in the average (mean +/- SEM) fractal dimension from
      1.15 +/- 0.01 to 1.29 +/- 0.01 and in the percentage of hyperactivated
      spermatozoa from 3 +/- 1% to 19 +/- 2%. These changes in hyperactivation were
      observed less often in sperm populations that had not been incubated for
      capacitation. All these changes partially adapted within 3-10 min, meaning that
      following the initial change and while being kept at the new temperature, the
      values of the measured motility parameters slowly and partially returned toward
      the original values. These results led us to conclude that spermatozoa direct
      their swimming in a temperature gradient by modulating the frequency of turns
      (both abrupt turns as in hyperactivation events and subtle turns) and speed in a
      way that favors swimming in the direction of the gradient. LIMITATIONS, REASONS
      FOR CAUTION: The conclusions were made on the basis of results obtained in
      temporal and steep temperature gradients. The conclusions for spatial, shallow
      gradients were made by extrapolation. WIDER IMPLICATIONS OF THE FINDINGS: This is
      the first study that reveals the behavior of human spermatozoa in thermotaxis.
      This behavior is very similar to that observed during human sperm chemotaxis,
      suggesting commonality of guidance mechanisms in mammalian spermatozoa. This
      study further substantiates the function of hyperactivation as a means to direct
      spermatozoa in guidance mechanisms. STUDY FUNDING/COMPETING INTERESTS: The
      authors have no conflict of interest and no funding to declare.

PMID- 25609240
TI  - Placental STAT3 signaling is activated in women with polycystic ovary syndrome.
AB  - STUDY QUESTION: Does polycystic ovary syndrome (PCOS) in women without pregnancy
      complications affect placental signal transducer and activator of transcription 3
      (STAT3) and mechanistic target of rapamycin (mTOR) signaling? SUMMARY ANSWER:
      Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS.
      WHAT IS KNOWN ALREADY: Women with PCOS have increased risk of poor pregnancy
      outcomes (e.g. restricted or accelerated fetal growth), indicating placental
      dysfunction. Placental STAT3 and mTOR pathways regulate placental function and
      indirectly affect fetal growth. STUDY DESIGN, SIZE, DURATION: In a case-control
      study, placental tissue and maternal blood were collected at delivery from 40
      control pregnant women and 38 PCOS women with uncomplicated pregnancy.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS were recruited at two
      medical centers and pregnant controls were recruited at one of these centers.
      Placental mRNA expression of genes encoding proteins related to steroid action,
      metabolic pathways and cytokines was analyzed by quantitative RT-PCR.
      Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western
      blot. Levels of sex steroids in serum were determined by mass spectrometry. MAIN
      RESULTS AND THE ROLE OF CHANCE: Placental P-STAT3 (Tyr-705) was increased in
      women with PCOS (P < 0.05) versus controls. Placental mTOR signaling was not
      affected in PCOS women when compared with controls. Circulating levels of
      androstenedione, androst-5-ene-3beta, 17beta-diol, testosterone, 5alpha
      dihydrotestosterone and etiocholanolone glucuronide were higher and estradiol
      lower in women with PCOS than in controls (all P < 0.05). No correlation between
      sex steroid levels in serum and P-STAT3 was observed. LIMITATIONS, REASONS FOR
      CAUTION: Women with PCOS and pregnancy complications were excluded to avoid the
      confounding effects of placental pathologies, which could modify STAT3 and mTOR
      signaling. Moreover, 97.4% of women with PCOS in the study displayed
      oligoamenorrhea at diagnosis. Thus, the current findings could be restricted to
      PCOS women with the oligo-anovulatory phenotype without pregnancy complications.
      WIDER IMPLICATIONS OF THE FINDINGS: Phosphorylation of STAT3 is increased in the
      placenta from women with PCOS and uncomplicated pregnancies, indicating that
      specific metabolic placental pathways are activated in the absence of obstetric
      and perinatal complications. STUDY FUNDING/COMPETING INTERESTS: The work was
      supported by the Swedish Medical Research Council (Project No. 2011-2732 and 2014
      2775); Jane and Dan Olsson Foundation, Wilhelm and Martina Lundgrens's Science
      Fund; Hjalmar Svensson Foundation (E.S.-V and M.M.); Adlerbert Research
      Foundation; Swedish federal government under the LUA/ALF agreement ALFFGBG-136481
      and 429501 and the Regional Research and Development agreement (VGFOUREG-5171, 
      11296 and -7861). MM thanks the Becas Chile Programme (Chile) and University of
      Chile for financial support through a postdoctoral fellowship. There are no
      competing interests.

PMID- 25609241
TI  - Triggering Different Brain States Using Asynchronous Serial Communication to the
      Rat Amygdala.
AB  - Inputting information to the brain through direct electrical microstimulation
      must consider how underlying neural networks encode information. One unexplored
      possibility is that a single electrode delivering temporally coded stimuli,
      mimicking an asynchronous serial communication port to the brain, can trigger the
      emergence of different brain states. This work used a discriminative fear
      conditioning paradigm in rodents in which 2 temporally coded microstimulation
      patterns were targeted at the amygdaloid complex. Each stimulus was a binary
      coded "word" made up of 10 ms bins, with 1's representing a single pulse
      stimulus: A-1001111001 and B-1110000111. During 3 consecutive retention tests
      (i.e., day-word: 1-B; 2-A, and 3-B), only binary-coded words previously paired
      with a foot-electroshock elicited proper aversive behavior. To determine the
      neural substrates recruited by the different stimulation patterns, c-Fos
      expression was evaluated 90 min after the last retention test. Animals
      conditioned to word-B, after stimulation with word-B, demonstrated increased
      hypothalamic c-Fos staining. Animals conditioned to word-A, however, showed
      increased prefrontal c-Fos labeling. In addition, prefrontal-cortex and
      hypothalamic c-Fos staining for, respectively, word-B- and word-A-conditioned
      animals, was not different than that of an unpaired control group. Our results
      suggest that, depending on the valence acquired from previous learning,
      temporally coded microstimulation activates distinct neural networks and
      associated behavior. 

PMID- 25609242
TI  - Motor Cortex Reorganization and Impaired Function in the Transition to Sustained
      Muscle Pain.
AB  - Primary motor cortical (M1) adaptation has not been investigated in the
      transition to sustained muscle pain. Daily injection of nerve growth factor (NGF)
      induces hyperalgesia reminiscent of musculoskeletal pain and provides a novel
      model to study M1 in response to progressively developing muscle soreness. Twelve
      healthy individuals were injected with NGF into right extensor carpi radialis
      brevis (ECRB) on Days 0 and 2 and with hypertonic saline on Day 4. Quantitative
      sensory and motor testing and assessment of M1 organization and function using
      transcranial magnetic stimulation were performed prior to injection on Days 0, 2,
      and 4 and again on Day 14. Pain and disability increased at Day 2 and increased
      further at Day 4. Reorganization of M1 was evident at Day 4 and was characterized
      by increased map excitability. These changes were accompanied by reduced
      intracortical inhibition and increased intracortical facilitation.
      Interhemispheric inhibition was reduced from the "affected" to the "unaffected"
      hemisphere on Day 4, and this was associated with increased pressure sensitivity
      in left ECRB. These data provide the first evidence of M1 adaptation in the
      transition to sustained muscle pain and have relevance for the development of
      therapies that seek to target M1 in musculoskeletal pain. 

PMID- 25609243
TI  - Unexpected drainage of pancreatic pseudocyst through the common bile duct.

PMID- 25609244
TI  - The lowest triplet states of bridged cis-2,2'-bithiophenes - theory vs.
      experiment.
AB  - Theoretical methods that were previously used to give a good quantitative
      description of the 3(1)Bu state of trans-2,2'-bithiophene are applied to
      characterize the lowest triplet states of three bridged cis-2,2'-bithiophenes:
      3,3'-cyclopentadithiophene (CPDT), 3,3'-dithienylpyrrole (DTP), and 3,3'
      dithienylthiophene (DTT). By obtaining highly accurate reproductions of the
      phosphorescence spectra of all three compounds, we rationalize the observed
      vibronic activity, further explore the performance of the applied theoretical
      methods, and address the quality of the reported experimental spectra. Over the
      course of this study we have, first, characterized the changes in the electronic
      structures between the ground state and the lowest triplet state and, second,
      expressed the related geometrical differences in terms of the Huang-Rhys factors.
      The Huang-Rhys factors have then been used to generate theoretical emission
      spectra with vibronic resolution. The applied procedure has yielded quantitative
      reproductions of the previously reported experimental phosphorescence spectra of
      DTT and DTP. The experimental spectrum of CPDT, on the other hand, turned out to
      be considerably narrower and intensity-deficient in its low energy region when
      compared with the theoretical results. Our experimental reinvestigation of the
      CPDT phosphorescence has given a refined spectrum that is significantly wider
      than the previously reported one, and is in nearly quantitative agreement with
      the theoretical prediction. This enabled us to attribute the observed discrepancy
      to an experimental artifact associated with the sensitivity characteristics of
      the commonly used photomultipliers. 

PMID- 25609245
TI  - Stromal expression of miR-21 in T3-4a colorectal cancer is an independent
      predictor of early tumor relapse.
AB  - BACKGROUND: MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the
      expression of multiple cancer-related target genes. miR-21 has been associated
      with progression of some types of cancer. Metastasis-associated protein1
      expression and loss of E-cadherin expression are correlated with cancer
      progression and metastasis in many cancer types. In advanced colorectal cancer,
      the clinical significance of miR-21 expression remains unclear. We aimed to
      investigate the impact of miR-21 expression in advanced colorectal cancer and its
      correlation with target proteins associated with colorectal cancer progression.
      METHODS: From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer
      treated with R0 surgical resection were included. Patients with neoadjuvant
      therapy and distant metastasis at presentation were excluded. The expression of
      miR-21 was investigated by in situ hybridization. Immunohistochemistry was used
      to detect E-cadherin and metastasis-associated protein1 expression. RESULTS: High
      stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer
      samples and was correlated with low E-cadherin expression (P = 0.019) and high
      metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer
      patients with high miR-21 expression had significantly shorter recurrence-free
      survival than those with low miR-21 expression. When analyzing colon and rectal
      cancer separately, high expression of miR-21 was an independent prognostic factor
      of unfavorable recurrence-free survival in T3-4a colon cancer patients (P =
      0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In
      a sub-classification analysis, high miR-21 expression was associated with shorter
      recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage
      III subgroup (P = 0.267). CONCLUSIONS: Stromal miR-21 expression is related to
      the expression of E-cadherin and metastasis-associated protein1 in colorectal
      cancer. Stage II colorectal cancer patients with high levels of miR-21 are at
      higher risk for tumor recurrence and should be considered for more intensive
      treatment.

PMID- 25609247
TI  - Nomograms to predict survival and the risk for developing local or distant
      recurrence in patients with rectal cancer treated with optional short-term
      radiotherapy.
AB  - BACKGROUND: In many European countries, short-term 5 * 5 Gy radiotherapy has
      become the standard preoperative treatment of patients with resectable rectal
      cancer. Individualized risk assessment might allow a better selection of patients
      who will benefit from postoperative treatment and intensified follow-up. PATIENTS
      AND METHODS: From patient's data from three European rectal cancer trials (N =
      2881), we developed multivariate cox nomograms reflecting the risk for local
      recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated
      variables were age, gender, tumour distance from the anal verge, the use of
      radiotherapy, surgical technique (total mesorectal excision/conventional
      surgery), surgery type (low anterior resection/abdominoperineal resection), time
      from randomization to surgery, residual disease (R0 versus R1 + 2), pT-stage, pN
      stage and surgical complications. RESULTS: Pathological T- and N-status are of
      vital importance for an accurate prediction of LR, DM and OS. Short-course
      radiotherapy reduces the rate of LR. The developed nomograms are capable of
      predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75
      (OS). The proposed stratification in risk groups allowed significant distinction
      between Kaplan-Meier curves for outcome. CONCLUSION: The developed nomograms can
      contribute to better individual risk prediction for LR, DM and OS for patients
      operated on rectal cancer. The practicality of the defined risk groups makes
      decision support in the consulting room feasible, assisting physicians to select
      patients for adjuvant therapy or intensified follow-up.

PMID- 25609246
TI  - A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or
      placebo in combination with gemcitabine as first-line therapy for metastatic
      adenocarcinoma of the pancreas: the GAMMA trial.
AB  - BACKGROUND: This double-blind, phase 3 study assessed the efficacy and safety of
      ganitumab combined with gemcitabine as first-line treatment of metastatic
      pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated
      metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive
      intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle)
      plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each
      cycle). The primary end point was overall survival (OS). Secondary end points
      included progression-free survival (PFS), safety, and efficacy by levels of
      circulating biomarkers. RESULTS: Overall, 322 patients were randomly assigned to
      placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was
      stopped based on results from a preplanned futility analysis; the final results
      are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in
      the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm
      [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI,
      6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397).
      Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months
      (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity
      was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed
      [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not
      associated with a treatment effect on OS or PFS by ganitumab. CONCLUSION:
      Ganitumab combined with gemcitabine had manageable toxicity but did not improve
      OS, compared with gemcitabine alone in unselected patients with metastatic
      pancreatic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01231347.

PMID- 25609248
TI  - Phase I and biomarker study of OPB-51602, a novel signal transducer and activator
      of transcription (STAT) 3 inhibitor, in patients with refractory solid
      malignancies.
AB  - BACKGROUND: The aim of this study was to determine the maximum-tolerated dose
      (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral,
      direct signal transduction activator of transcription 3 (STAT3) inhibitor, in
      patients with refractory solid tumors. PATIENTS AND METHODS: Three cohorts were
      studied: cohort A, a sequential dose escalation of OPB-51602 administered
      intermittently (days 1-14 every 21 days); cohort B, an expansion cohort
      evaluating the dose lower than the MTD; cohort C, evaluating continuous daily
      dosing. RESULTS: Fifty-one patients were studied at 2, 4, and 5 mg per day
      dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade
      3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent
      dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose
      was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C
      investigated 4 mg continuously. Common toxicities included fatigue,
      nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug
      induced pneumonitis occurred in two patients in cohort C. Continuous dosing was
      associated with a higher incidence of peripheral neuropathy and a lower mean
      relative dose intensity, compared with intermittent dosing. Steady-state
      pharmacokinetics was characterized by high oral clearance, mean elimination half
      life ranging from 44 to 61 h, and a large terminal-phase volume of distribution.
      An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602.
      Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3
      (Tyr(705)) inhibition following exposure. Two patients achieved partial responses
      at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor
      receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior
      EGFR tyrosine kinase inhibitor exposure. CONCLUSION: OPB-51602 demonstrates
      promising antitumor activity, particularly in NSCLC. Its long half-life and
      poorer tolerability of continuous dosing, compared with intermittent dosing,
      suggest that less frequent dosing should be explored. CLINICALTRIALSGOV
      IDENTIFIER: NCT01184807.

PMID- 25609249
TI  - Structural view and substrate specificity of papain-like protease from avian
      infectious bronchitis virus.
AB  - Papain-like protease (PLpro) of coronaviruses (CoVs) carries out proteolytic
      maturation of non-structural proteins that play a role in replication of the
      virus and performs deubiquitination of host cell factors to scuttle antiviral
      responses. Avian infectious bronchitis virus (IBV), the causative agent of
      bronchitis in chicken that results in huge economic losses every year in the
      poultry industry globally, encodes a PLpro. The substrate specificities of this
      PLpro are not clearly understood. Here, we show that IBV PLpro can degrade
      Lys(48)- and Lys(63)-linked polyubiquitin chains to monoubiquitin but not linear
      polyubiquitin. To explain the substrate specificities, we have solved the crystal
      structure of PLpro from IBV at 2.15-A resolution. The overall structure is
      reminiscent of the structure of severe acute respiratory syndrome CoV PLpro.
      However, unlike the severe acute respiratory syndrome CoV PLpro that lacks
      blocking loop (BL) 1 of deubiquitinating enzymes, the IBV PLpro has a short BL1
      like loop. Access to a conserved catalytic triad consisting of Cys(101),
      His(264), and Asp(275) is regulated by the flexible BL2. A model of ubiquitin
      bound IBV CoV PLpro brings out key differences in substrate binding sites of
      PLpros. In particular, P3 and P4 subsites as well as residues interacting with
      the beta-barrel of ubiquitin are different, suggesting different catalytic
      efficiencies and substrate specificities. We show that IBV PLpro cleaves peptide
      substrates KKAG-7-amino-4-methylcoumarin and LRGG-7-amino-4-methylcoumarin with
      different catalytic efficiencies. These results demonstrate that substrate
      specificities of IBV PLpro are different from other PLpros and that IBV PLpro
      might target different ubiquitinated host factors to aid the propagation of the
      virus. 

PMID- 25609250
TI  - Presenilin-like GxGD membrane proteases have dual roles as proteolytic enzymes
      and ion channels.
AB  - The GxGD proteases function to cleave protein substrates within the membrane. As
      these proteases contain multiple transmembrane domains typical of ion channels,
      we examined if GxGD proteases also function as ion channels. We tested the
      putative dual function by examining two archeobacterial GxGD proteases (PSH and
      FlaK), with known three-dimensional structures. Both are in the same GxGD family
      as presenilin, a protein mutated in Alzheimer Disease. Here, we demonstrate that
      PSH and FlaK form cation channels in lipid bilayers. A mutation that affected the
      enzymatic activity of FlaK rendered the channel catalytically inactive and
      altered the ion selectivity, indicating that the ion channel and the catalytic
      activities are linked. We report that the GxGD proteases, PSH and FlaK, are true
      "chanzymes" with interdependent ion channel and protease activity conferred by a
      single structural domain embedded in the membrane, supporting the proposal that
      higher-order proteases, including presenilin, have channel function. 

PMID- 25609251
TI  - Tyrosyl-DNA phosphodiesterase I catalytic mutants reveal an alternative
      nucleophile that can catalyze substrate cleavage.
AB  - Tyrosyl-DNA phosphodiesterase I (Tdp1) catalyzes the repair of 3'-DNA adducts,
      such as the 3'-phosphotyrosyl linkage of DNA topoisomerase I to DNA. Tdp1
      contains two conserved catalytic histidines: a nucleophilic His (His(nuc)) that
      attacks DNA adducts to form a covalent 3'-phosphohistidyl intermediate and a
      general acid/base His (His(gab)), which resolves the Tdp1-DNA linkage. A His(nuc)
      to Ala mutant protein is reportedly inactive, whereas the autosomal recessive
      neurodegenerative disease SCAN1 has been attributed to the enhanced stability of
      the Tdp1-DNA intermediate induced by mutation of His(gab) to Arg. However, here
      we report that expression of the yeast His(nuc)Ala (H182A) mutant actually
      induced topoisomerase I-dependent cytotoxicity and further enhanced the
      cytotoxicity of Tdp1 His(gab) mutants, including H432N and the SCAN1-related
      H432R. Moreover, the His(nuc)Ala mutant was catalytically active in vitro, albeit
      at levels 85-fold less than that observed with wild type Tdp1. In contrast, the
      His(nuc)Phe mutant was catalytically inactive and suppressed His(gab) mutant
      induced toxicity. These data suggest that the activity of another nucleophile
      when His(nuc) is replaced with residues containing a small side chain (Ala, Asn,
      and Gln), but not with a bulky side chain. Indeed, genetic, biochemical, and mass
      spectrometry analyses show that a highly conserved His, immediately N-terminal to
      His(nuc), can act as a nucleophile to catalyze the formation of a covalent Tdp1
      DNA intermediate. These findings suggest that the flexibility of Tdp1 active site
      residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl
      intermediates and provide the rationale for developing chemotherapeutics that
      stabilize the covalent Tdp1-DNA intermediate. 

PMID- 25609253
TI  - Laboratory Automation and Intra-Laboratory Turnaround Time: Experience at the
      University Hospital Campus Bio-Medico of Rome.
AB  - Intra-laboratory turnaround time (TAT) is a key indicator of laboratory
      performance. Improving TAT is a complex task requiring staff education, equipment
      acquisition, and adequate TAT monitoring. The aim of the present study was to
      evaluate the intra-laboratory TAT after laboratory automation implementation
      (June 2013-June 2014) and to compare it to that in the preautomation period (July
      2012-May 2013). Intra-laboratory TAT was evaluated both as the mean TAT
      registered and the percentage of outlier (OP) exams. The mean TAT was 36, 38, and
      34 min during the study periods, respectively. These values respected the goal
      TAT established at 45 min. The OP, calculated at 45 min as well as at 60 min,
      decreased from 26 to 21 and from 11 to 5, respectively. From a focused analysis
      on blood count cell, troponin I, and prothrombin (PT) test, TAT improvement was
      more evident for tests requiring longer preanalytical process. The follow-up of
      TAT from June 2013 to June 2014 revealed the reduction of the mean TAT as well as
      of the OP exams after automation implementation and that automation more strongly
      affects the test in the preanalytical phase including centrifugation of the
      sample, such as troponin I and PT. 

PMID- 25609252
TI  - Site-specific phosphorylation of kindlin-3 protein regulates its capacity to
      control cellular responses mediated by integrin alphaIIbbeta3.
AB  - The contributions of integrins to cellular responses depend upon their
      activation, which is regulated by binding of proteins to their cytoplasmic tails.
      Kindlins are integrin cytoplasmic tail binding partners and are essential for
      optimal integrin activation, and kindlin-3 fulfills this role in hematopoietic
      cells. Here, we used human platelets and human erythroleukemia (HEL) cells, which
      express integrin alphaIIbbeta3, to investigate whether phosphorylation of kindlin
      3 regulates integrin activation. When HEL cells were stimulated with
      thrombopoietin or phorbol 12-myristate 13-acetate (PMA), alphaIIbbeta3 became
      activated as evidenced by binding of an activation-specific monoclonal antibody
      and soluble fibrinogen, adherence and spreading on fibrinogen, colocalization of
      beta3 integrin and kindlin-3 in focal adhesions, and enhanced beta3 integrin
      kindlin-3 association in immunoprecipitates. Kindlin-3 knockdown impaired
      adhesion and spreading on fibrinogen. Stimulation of HEL cells with agonists
      significantly increased kindlin-3 phosphorylation as detected by mass
      spectrometric sequencing. Thr(482) or Ser(484) was identified as a
      phosphorylation site, which resides in a sequence not conserved in kindlin-1 or
      kindlin-2. These same residues were phosphorylated in kindlin-3 when platelets
      were stimulated with thrombin. When expressed in HEL cells, T482A/S484A kindlin-3
      decreased soluble ligand binding and cell spreading on fibrinogen compared with
      wild-type kindlin-3. A membrane-permeable peptide containing residues 476-485 of
      kindlin-3 was introduced into HEL cells and platelets; adhesion and spreading of
      both cell types were blunted compared with a scrambled control peptide. These
      data identify a role of kindlin-3 phosphorylation in integrin beta3 activation
      and provide a basis for functional differences between kindlin-3 and the two
      other kindlin paralogs. 

PMID- 25609254
TI  - Standardized 3D Bioprinting of Soft Tissue Models with Human Primary Cells.
AB  - Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To
      use 3D models in substance testing and regenerative medicine, reproducibility and
      standardization are important. Bioprinting offers not only automated
      standardizable processes but also the production of complex tissue-like
      structures in an additive manner. We developed an all-in-one bioprinting solution
      to produce soft tissue models. The holistic approach included (1) a bioprinter in
      a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user
      friendly software, (4) the capability to print in standard labware for high
      throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell
      compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof
      of-concept study, skin as a reference soft tissue model was printed. To produce
      dermal equivalents, primary human dermal fibroblasts were printed in alternating
      layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the
      models were remodeled and fully populated with viable and spreaded fibroblasts.
      Primary human dermal keratinocytes were seeded on top of dermal equivalents, and
      epidermis-like structures were formed as verified with hematoxylin and eosin
      staining and immunostaining. However, a fully stratified epidermis was not
      achieved. Nevertheless, this is one of the first reports of an integrative
      bioprinting strategy for industrial routine application. 

PMID- 25609255
TI  - A Low-Cost and High-Resolution Droplet Position Detector for an Intelligent
      Electrowetting on Dielectric Device.
AB  - A low-cost and high-resolution capacitive-to-digital converter integrated circuit
      is used for droplet position detection in a digital microfluidic system. A field
      programmable gate array FPGA is used as the integrated logic hub of the system
      for a highly reliable and efficient control of the circuit. A fast-fabricating
      PCB (printed circuit board) substrate microfluidic system is proposed. Smaller
      actuation threshold voltages than those previously reported are obtained.
      Droplets (3 uL) are actuated by using a 200 V, 500 Hz modulating pulsed voltage.
      Droplet positions can be detected and displayed on a PC-based 3D animation in
      real time. The actuators and the capacitance sensing circuits are implemented on
      one PCB to reduce the size of the system. With the capacitive droplet position
      detection system, the PCB-based electrowetting on dielectric device (EWOD)
      reported in this work has promise in automating immunohistochemistry experiments.

PMID- 25609256
TI  - Diagnosis and Management of Hepatitis C Virus Infection.
AB  - The hepatitis C virus (HCV) infects more than 200 million people globally, with
      increasing incidence, especially in developing countries. HCV infection
      frequently progresses to chronic liver disease, creating a heavy economic burden
      on resource-poor countries and lowering patient quality of life. Effective HCV
      diagnosis, treatment selection, and treatment monitoring are important in
      stopping disease progression. Serological assays, which detect anti-HCV
      antibodies in the patient after seroconversion, are used for initial HCV
      diagnosis. Qualitative and quantitative molecular assays are used to confirm
      initial diagnosis, determine viral load, and genotype the dominant strain. Viral
      load and genotype information are used to guide appropriate treatment. Various
      other biomarker assays are performed to assess liver function and enable disease
      staging. Most of these diagnostic methods are mature and routinely used in high
      resource countries with well-developed laboratory infrastructure. Few
      technologies, however, are available that address the needs of low-resource areas
      with high HCV prevalence, such as Africa and Southeast Asia. 

PMID- 25609257
TI  - Charge and charge-pair mutations alter the rate of assembly and structural
      properties of apolipoprotein C-II amyloid fibrils.
AB  - The misfolding, aggregation, and accumulation of proteins as amyloid fibrils is a
      defining characteristic of several debilitating diseases. Human apolipoprotein C
      II (apoC-II) amyloid fibrils are representative of the fibrils formed by a number
      of plasma apolipoproteins implicated in amyloid-related disease. Previous
      structural analyses identified a buried charge pair between residues K30 and D69
      within apoC-II amyloid fibrils. We have investigated the effects of amino acid
      substitutions of these residues on apoC-II fibril formation. Two point mutations
      of apoC-II, D69K and K30D, as well as a reversed ion-pair mutant containing both
      mutations (KDDK) were generated. Fibril formation by the double mutant, apoC-II
      KDDK, and apoC-II D69K was enhanced compared to that of wild-type (WT) apoC-II,
      while apoC-II K30D lacked the ability to form fibrils under standard conditions.
      Structural analyses showed that WT apoC-II, apoC-II D69K, and apoC-II KDDK
      fibrils have similar secondary structures and morphologies. Size distribution
      analyses revealed that apoC-II D69K fibrils have a broader range of fibril sizes
      while apoC-II KDDK fibrils showed an increased frequency of closed fibrillar
      loops. ApoC-II D69K fibrils exhibited reduced thioflavin T binding capacity
      compared to that of fibrils formed by WT apoC-II and apoC-II KDDK. These results
      indicate that specific charge and charge-pair mutations within apoC-II
      significantly alter the ability to form fibrils and that position 69 within apoC
      II plays a key role in the rate-limiting step of apoC-II fibril formation. 

PMID- 25609258
TI  - Sexual behaviour among young Danes aged 15-29 years: a cross-sectional study of
      core indicators.
AB  - OBJECTIVES: Sexually transmitted infections and unwanted pregnancies occur at
      high rates among youth. Understanding sexual behaviour is essential for planning
      and implementing future effective preventive interventions. The present study
      examines the sexual behaviour in the general Danish population aged 15-29 years
      using the core indicators recommended by the European Centre for Disease
      Prevention and Control. METHODS: A nationwide cross-sectional study was conducted
      in Denmark among a random sample of 20 000 men and women in 2012. Respondents
      completed a web-based sexual behaviour questionnaire and data were linked to a
      nationally held demographic database. Core indicators for sexual behaviour
      frequency stratified by gender are presented as unweighted and weighted data
      after consideration of sociodemographic differences between respondents and non
      respondents. RESULTS: Response rate was 20.4%. Condoms were used at sexual debut
      by 69.9% of women and 62.3% of men, while 14.3% of women and 15.1% of men used no
      contraceptives at sexual debut. Half of the respondents used condom alone at the
      latest sexual encounter with a steady partner (women 51.8%, men 55.2%), while 10%
      used no contraceptives. Having a sexual encounter with a casual partner decreased
      the likelihood of using condoms (women 43.7%, men 49.5%) and increased the
      likelihood of using no contraceptives (women 14.8%, men 20.9%). Data on sexual
      behaviour characteristics showed only minor changes when weighted for non
      response. CONCLUSIONS: The findings call for interventions addressing the use of
      appropriate contraception at sexual debut and at last sexual encounter; this
      seems particularly important when the sexual partner is a casual partner.

PMID- 25609260
TI  - Launching a new era for behavioural surveillance.

PMID- 25609259
TI  - Ecological analysis examining the association between census tract-level
      incarceration and reported chlamydia incidence among female adolescents and young
      adults in San Francisco.
AB  - OBJECTIVES: Incarceration has been linked to increased risk of sexually
      transmitted infections (STIs). We conducted a census tract-level ecological
      analysis to explore the relationship between neighbourhood incarceration rates
      and chlamydia incidence among adolescent girls and young women under age 25 in
      San Francisco in 2010 to focus public health efforts in neighbourhoods at risk.
      METHODS: Female chlamydial cases under age 25 that were reported to the San
      Francisco Department of Public Health in 2010 were geocoded to census tract, and
      chlamydia incidence was calculated. Addresses of incarcerated individuals were
      geocoded, and census tract-specific incarceration was estimated. American
      Community Survey data from 2005 to 2009 provided tract-specific survey estimates
      of demographic and socioeconomic characteristics of communities to allow for
      evaluation of potential census tract-level confounders. A Poisson mixed model was
      used to assess the relationship of census tract-level incarceration rate with
      chlamydial case rate. RESULTS: Accounting for spatial dependence in neighbouring
      regions, there was a positive association between incarceration rates and
      chlamydia incidence in young women under age 25 in San Francisco, and this
      association decreased as poverty increased, after controlling for other risk
      factors in the model. CONCLUSIONS: This ecological analysis supports the
      neighbourhood role of incarceration in the risk of chlamydia among young women.
      These results have important implications for directing limited public health
      resources to local areas at risk in order to geographically focus prevention
      interventions and provide improved access to STI services in specific
      neighbourhoods with high incarceration rates.

PMID- 25609261
TI  - Knowledge of occupational exposure to HIV: a cross sectional study of healthcare
      workers in Tumbi and Dodoma hospitals, Tanzania.
AB  - BACKGROUND: Insufficient knowledge on blood-borne pathogens has been identified
      as a factor that influences occupational exposure to needle stick and sharps
      injuries. The objective of this study was to assess healthcare workers' knowledge
      on occupational exposure to HIV. METHODS: A cross sectional survey was conducted
      at Tumbi designated regional hospital and Dodoma regional hospital, Tanzania in
      February 2012. A self-administered questionnaire was used to capture information
      on knowledge of occupational exposure to HIV infection. RESULTS: A total of 401
      healthcare workers responded to a self-administered questionnaire. High
      proportion of healthcare workers (96.3%) understood that they are at risk of
      occupational exposure to HIV. The majority of healthcare workers trained on post
      exposure prophylaxis procedure and use of personal protective equipment were
      clinicians (87.1% and 71.4% respectively) and nurses (81.8% and 74.6%
      respectively). Over a quarter of the healthcare workers were not aware of whom to
      contact in the event of occupational exposure. One third of healthcare workers
      did not have comprehensive knowledge on causes of occupational HIV transmission
      and did not know when post exposure prophylaxis is indicated. Healthcare workers
      not trained on the use of person protective equipment were less likely to have
      comprehensive knowledge on occupational exposure to HIV (OR = 0.5; 95% CI 0.3 -
      0.9). Knowledge on causes of occupational exposure varied with the cadre of
      healthcare workers. Nurses were more likely to have comprehensive knowledge on
      occupational exposure to HIV than non-clinical staff (OR = 2.6; 95% CI 1.5 -
      4.5). CONCLUSION: A substantial proportion of studied healthcare workers had
      little knowledge on occupational exposure to HIV and was not aware of a contact
      person in the event of occupational exposure to HIV. Training on post exposure
      prophylaxis and infection prevention and control including the use of person
      protective equipment provided to nurses and clinicians should be extended to
      other clinical and non-clinical hospital staff.

PMID- 25609262
TI  - Migraine and hemorrhagic stroke: data from general practice.

PMID- 25609263
TI  - Giant pandas failed to show mirror self-recognition.
AB  - Mirror self-recognition (MSR), i.e., the ability to recognize oneself in a
      mirror, is considered a potential index of self-recognition and the foundation of
      individual development. A wealth of literature on MSR is available for social
      animals, such as chimpanzees, Asian elephants and dolphins, yet little is known
      about MSR in solitary mammalian species. We aimed to evaluate whether the giant
      panda can recognize itself in the mirror, and whether this capacity varies with
      age. Thirty-four captive giant pandas (F:M = 18:16; juveniles, sub-adults and
      adults) were subjected to four mirror tests: covered mirror tests, open mirror
      tests, water mark control tests, and mark tests. The results showed that, though
      adult, sub-adult and juvenile pandas exposed to mirrors spent similar amounts of
      time in social mirror-directed behaviors (chi(2) = 0.719, P = 0.698), none of
      them used the mirror to touch the mark on their head, a self-directed behavior
      suggesting MSR. Individuals of all age groups initially displayed attacking,
      threatening, foot scraping and backwards walking behaviors when exposed to their
      self-images in the mirror. Our data indicate that, regardless of age, the giant
      pandas did not recognize their self-image in the mirror, but instead considered
      the image to be a conspecific. Our results add to the available information on
      mirror self-recognition in large mammals, provide new information on a solitary
      species, and will be useful for enclosure design and captive animal management.

PMID- 25609264
TI  - Prospective double-blind randomized study on the efficacy and safety of an n-3
      fatty acid enriched intravenous fat emulsion in postsurgical gastric and
      colorectal cancer patients.
AB  - BACKGROUND: A lipid emulsion composed of soybean oil (long-chain triglycerides,
      LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids
      (PUFAs) was evaluated for immune-modulation efficacy, safety, and tolerance in
      patients undergoing major surgery for gastric and colorectal cancer. METHODS: In
      a prospective, randomized, double-blind study, 99 patients with gastric and
      colorectal cancer receiving elective surgery were recruited and randomly assigned
      to either the study group, receiving the n-3 PUFAs enriched intravenous fat
      emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of
      soybean oil and MCTs (0.8 - 1.5 g . kg-1 . day-1) as part of total parenteral
      nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety
      and efficacy parameters were assessed on day -1 and post-operative visits on day
      1, 3, and 7. Adverse events were documented daily and compared between the
      groups. RESULTS: Pro-inflammatory markers, laboratory parameters, and adverse
      events did not differ prominently between the 2 groups, with the exception of net
      changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high
      density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the
      study group, while the net increase of triglyceride and decrease of HDL was
      significantly lower. CONCLUSIONS: The n-3 PUFA-enriched IVFE showed improvements
      in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were
      comparable. In patients with severe stress, there is an inflammation-attenuating
      effect of n-3 PUFAs. Further, adequately powered clinical trials will be
      necessary to address this question in postsurgical GI cancer patients. TRIAL
      REGISTRATION: US ClinicalTrials.gov NCT00798447.

PMID- 25609267
TI  - Construction of an infectious plasmid clone of Muscovy duck parvovirus by TA
      cloning and creation of a partially attenuated strain.
AB  - Muscovy duck parvovirus (MDPV) infection is a highly contagious and fatal disease
      of Muscovy ducklings. The infectious clone methodology is a valuable tool to
      study the pathogenic mechanisms of viruses, but no infectious clone of MDPV is
      yet available. In this study, a plasmid clone containing the full-length genome
      of MDPV was constructed using the TA cloning methodology. This MDPV clone was
      found to be infectious after transfection of primary Muscovy duck embryo
      fibroblast cells and passage in embryonated Muscovy duck eggs. Site-directed
      mutagenesis showed that the K75N mutation in the VP1 protein of MDPV resulted in
      the partial attenuation of the virus. The availability of an MDPV infectious
      clone can facilitate investigation of the pathogenic mechanisms of MDPV and
      development of vaccines against diseases caused by MDPV. 

PMID- 25609265
TI  - Prescribing efficiency of proton pump inhibitors in China: influence and future
      directions.
AB  - BACKGROUND: Pharmaceutical expenditure is currently rising by 16% per annum in
      China, greater in recent years. Initiatives to moderate growth include drug
      pricing regulations, essential medicine lists and encouraging generic
      prescribing. These are principally concentrated in hospitals, which currently
      account for over 80% of total pharmaceutical expenditure. However, no monitoring
      of prescribing and perverse incentives encouraging physicians and hospitals to
      profit from drug procurement encourages irrational prescribing. This includes
      greater utilisation of originators versus generics as well as injectables when
      cheaper oral equivalents are available. The objective of the paper is to assess
      changes in proton pump inhibitor (PPI) utilisation and expenditure in China as
      more generics become available including injectables. METHODS: Observational
      retrospective study of PPI utilisation and procured expenditure between 2004 and
      2013 in the largest teaching hospital in Chongqing District as representative of
      China. RESULTS: Appreciable increase in PPI utilisation during the study period
      rising 10.4 fold, with utilisation of generics rising faster than originators.
      Oral generics reached 84% of total oral preparations in 2013 (defined daily dose
      basis), with generic injectables 93% of total injectables by 2013. Injectables
      accounted for 42% of total PPI utilisations in 2008 and 2009 before falling to
      below 30%. Procured prices for oral preparations reduced over time (-34%).
      Generic oral omeprazole in 2010 was 87% below 2004 originator prices, mirroring
      reductions seen in Western Europe. Injectable prices also decreased over time (
      19%). However, injectables typically 4.3 to 6.8 fold more expensive than
      equivalent orals - highest for injectable lansoprazole at 13.4 to 18.0 fold. High
      utilisation of more expensive oral PPIs as well as injectables meant that PPI
      expenditure increased 10.1 fold during the study period. Lower use of
      injectables, and only oral generic omeprazole, would result in accumulated
      savings of CNY249.65 million, reducing total accumulated expenditure by 84%.
      CONCLUSIONS: Encouraging to see high utilisation of generic PPIs and low prices
      for oral generics. However, considerable opportunities to enhance prescribing
      efficiency through greater use of oral generic omeprazole.

PMID- 25609266
TI  - Carotid stenosis: from diagnosis to management, where do we stand?
AB  - Carotid atherosclerosis is implicated in 20-30 % of strokes. However, the annual
      risk of stroke in patients with asymptomatic carotid stenosis is less than 5 %.
      Symptomatic carotid stenosis poses a greater risk for recurrent stroke with
      estimates as high as 15 % per year. This paper aims to raise awareness of
      populations at risk for carotid stenosis, the role of carotid screening and the
      sensitivity and specificity of various diagnostic modalities. The results of
      previous trials that support current guidelines for management of symptomatic and
      asymptomatic carotid stenosis will also be reviewed. 

PMID- 25609268
TI  - Triangular fibrocartilage complex tears.

PMID- 25609269
TI  - A2 pulley integrity and the strength of flexor tendon repair: a biomechanical
      study in a chicken model.
AB  - PURPOSE: This study assesses the influence of A2 pulley integrity on the strength
      of the repair. METHOD: Part 1- The flexor digitorum profundus (FDP) tendons of 72
      Cobb chicken feet were severed and repaired in the region of the A2 pulley using
      a modified Kessler core suture and an epitendinous suture. The A2 pulley was
      either left intact, divided for 50% of its length, or divided in its entirety.
      The distal interphalangeal joint was fixed at a position of 20 degrees , 40
      degrees  or 60 degrees  of joint flexion. The load to failure, integrity of the
      A2 pulley and the site of tendon failure were analysed. Part 2- A further 32
      chicken feet were used to exclude the effects of freezing and thawing on results
      and to analyse differences when using a core suture only. RESULTS: No difference
      in failure load between any of the test groups or subgroups was identified. The
      integrity of the A2 pulley was preserved in all specimens. The most common cause
      of failure was distal suture pull-out. DISCUSSION: This study does not
      demonstrate that release of the A2 pulley provides an advantage in increasing
      tendon repair strength. Division of 50% of the A2 pulley does not predispose to
      pulley rupture. Flexor tendon repair strength did not alter with distal
      interphalangeal joint flexion between 20 degrees  and 60 degrees . CLINICAL
      RELEVANCE: The findings of this study do not support division of the A2 pulley to
      prevent flexor tendon repair failure if repair methods of appropriate strength
      are utilised.

PMID- 25609270
TI  - Influence of different length of core suture purchase among suture row on the
      strength of 6-strand tendon repairs.
AB  - In multi-strand suture methods consisting of several suture rows, the different
      length of core suture purchase between each suture row may affect the strength of
      repairs. We evaluated the influence of the different length of core suture
      purchase between each suture row on the strength of 6-strand tendon repairs.
      Rabbit flexor tendons were repaired by using a triple-looped suture technique in
      which the suture purchase length in each suture row was modified. Group 1, all
      lengths are 8-mm. Group 2, all lengths are 10-mm. Group 3, two are 10-mm and one
      is 8-mm. Group 4, one is 10-mm and two are 8-mm. The repaired tendons were
      subjected to load-to-failure test. The gap strength was significantly greater in
      Group 1 and Group 2 than in Group 3 and Group 4. This study demonstrates that
      maintaining equal core suture purchase lengths of each suture row increases the
      gap resistance.

PMID- 25609271
TI  - Cross-cultural adaptation, validation, and reliability of the Michigan Hand
      Outcomes Questionnaire among Persian population.
AB  - We aimed to validate a cross-culturally adapted version of the Persian Michigan
      Hand Outcomes Questionnaire (MHOQ). We followed the Beaton's guideline to
      translate the questionnaire to Persian. We administered the final version to 223
      patients among which 79 patients returned 3 days later to respond to the Persian
      MHOQ for the second time. In the first visit, respondents also filled the
      Disabilities of the Arm Shoulder and Hand (DASH) and rated the pain based on the
      Visual Analogue Scale (VAS). Cronbach's alpha for the total MHOQ was 0.79 which
      showed good internal consistency. Intraclass correlation coefficient (ICC) for
      the total MHOQ was 0.84 which demonstrated good reliability between test and
      retest. The absolute correlation coefficient between total MHOQ and the DASH was
      as high as 0.74. Persian version of the MHOQ proved to be a reliable and valid
      instrument to be implemented among Persian population with the hand and wrist
      disorders.

PMID- 25609272
TI  - The Greek version of the Hand20 questionnaire: crosscultural translation,
      reliability and construct validity.
AB  - The English version of Hand20 questionnaire was translated into Greek and
      cultural adaptation was performed. The validity was assessed in 134 patients with
      a variety of upper limb disorders. A comparison of Hand20 and DASH was also
      performed. All patients completed EQ-5D, Hand20 and DASH questionnaire. Test
      retest reliability was assessed in a subgroup of 37 patients. We assessed the
      convergent validity of Hand20 by correlating its scores to DASH and EQ-5D scores.
      We also compared the completeness of Hand20 and DASH. We found no statistically
      significant differences in Hand20 scores between the 1st and 2nd measurements as
      well as a strong correlation between Hand20 and the other two questionnaires.
      There were also better rates of response and fewer missing data even in elderly
      individuals.

PMID- 25609273
TI  - Neuropathic pain in brachial plexus injury.
AB  - BACKGROUND: In Thailand, brachial plexus injury is a common traumatic injury that
      affects the function of the upper extremity. The current treatments focus mainly
      on improving the motor and sensory function. Apart from the motor and sensory
      deficit, these patients usually suffer from pain. OBJECTIVE: The purpose of this
      study was to determine the prevalence and factors that relate to neuropathic pain
      in patients with brachial plexus injury. METHODS: We collected data from March
      2008 to July 2011. The DN4 Questionnaire was used to diagnose neuropathic pain in
      95 patients. RESULTS: The prevalence of neuropathic pain was as high as 76%.
      Majority of patients presented with hypoesthesia to pin prick, hypoesthesia to
      touch and numbness. Severity of neuropathic pain was significantly correlated
      with the type of brachial plexus injury. There was no difference between
      demographic characteristics of patients. CONCLUSION: Our study showed that the
      prevalence of neuropathic pain was high in brachial plexus injured patients.
      Therefore, surgeons should be aware of this common, yet underestimated, problem
      in brachial plexus injured patients.

PMID- 25609274
TI  - Impact of phrenic nerve paralysis on the surgical outcome of intercostal nerve
      transfer.
AB  - Brachial plexus injuries (BPI) can be complicated by diaphragmatic paralysis
      (DP). This study determined the influence of DP on biceps brachii (BB) recovery
      after intercostal nerve transfer (ICNT) for BPI and investigated the respiratory
      complications of ICNT. The study included 100 patients, 84 showing no DP in
      preoperative and early postoperative chest radiographic images (non-DP group) and
      16 with DP that persisted for over one year after surgery (DP group). The
      postoperative reinnervation time did not differ between groups. BB strength one
      year after surgery was lower in the DP group than non-DP group (p = 0.0007). No
      differences were observed 2-3 years after surgery. In the DP group, four patients
      had respiratory symptoms that affected daily activities and their outcomes
      deteriorated (p = 0.04). Phrenic nerve transfer should not be combined with ICNT
      in patients with poor respiratory function because of the high incidence of
      respiratory complications.

PMID- 25609275
TI  - The tricipital aponeurosis--a reliable soft tissue landmark for humeral plating.
AB  - This study aims to identify the relationship of the radial nerve as it descends
      across the humerus with reference to a reliable soft tissue landmark, the
      tricipital aponeurosis. Following cadaveric dissection of 10 adult humerii, the
      radial nerve was located as it crossed the lateral midsagittal point of the
      humeral diaphysis. A horizontal line was then subtended medially from this point
      to another line subtended vertically from the lateral border of the tricipital
      aponeurosis. The vertical distance from this intersection to the lateral apex of
      the aponeurosis was recorded in three positions (full flexion, 90 degrees  of
      flexion and full extension). The location of the radial nerve on the posterior
      aspect of the humeral diaphysis to the medial apex of the tricipital aponeurosis
      was also noted. In 90 degrees  of flexion the radial nerve at the lateral
      midsagittal point of the humerus was 0.9 mm proximal to the lateral apex of the
      tricipital aponeurosis. Flexion and extension of the elbow changed the interval
      to 16.3 mm (nerve proximal) in full flexion and 7.1 mm in full extension (nerve
      distal). On the posterior aspect of the humerus the radial nerve was 21.8 mm
      proximal to the medial aspect of the tricipital aponeurosis. The aponeurosis
      provides a reference point from which the nerve can be easily located on the
      lateral aspect of the humerus intraoperatively in a range of positions, whilst
      the medial apex provides a guide to the location of the nerve on the posterior
      aspect of the arm.

PMID- 25609276
TI  - Clinical radiographic features of the wrist without osteoarthritis and its
      relations to age and sex in Japanese.
AB  - The purpose of this study was to identify a clinical radiographic features
      containing the measurements of carpal alignment, configuration, and joint space
      width of the wrist without osteoarthritis (OA) in Japanese. We also aimed to
      analyse age-related correlations in these parameters with reference to the
      difference between men and women. A total of 184 cases were analysed to establish
      the following relations: (1) Sex-related differences in the morphology and joint
      space width of the wrist without OA; (2) correlation coefficient between these
      parameters and age according to sex. This study suggests that carpal height ratio
      (CHR) was higher in men than in women. Also the ulnar variance (UV) increased and
      the radial inclination (RI) decreased with age in both men and women, and the
      volar tilt (VT) decreased with age in women.

PMID- 25609277
TI  - Radial nerve lacerations--the outcome of end-to-end repairs in penetrating
      trauma.
AB  - Due to its mostly motor content, repair of the radial nerve is considered to
      yield favourable results. This is despite the fact that there are limited studies
      looking at the outcomes of end-to-end repair secondary to sharp penetrating
      trauma. We retrospectively reviewed the outcome of a series of repaired level 2
      and level 3 radial nerves following penetrating stab injuries. Twenty-seven cases
      with adequate follow-up were included. All the patients underwent direct end-to
      end repair. We evaluated the motor recovery of the target muscles using the
      British Medical Research Council (MRC) grading system. Wrist extension recovered
      in 93% of cases at a mean of six months. Finger extension recovered in 74% and
      thumb extension in 52% of cases within the follow-up period. We conclude that end
      to-end repair is possible in the majority of level 2 and level 3 radial nerve
      lacerations secondary to penetrating stab injuries. Acceptable results can be
      expected.

PMID- 25609278
TI  - Biphasic motion of the median nerve in the normal Asian population.
AB  - BACKGROUND: The biomechanical interaction between the median nerve and the flexor
      tendons is an important consideration in Carpal tunnel syndrome (CTS). We aim to
      quantify the displacement and compressive deformation pattern of the median nerve
      in various stages of finger flexion in the normal population at the inlet of the
      carpal tunnel. METHODS: Transverse ultrasounds images were taken at the carpal
      tunnel inlet during full-extension, mid-flexion and full flexion. The
      displacement, distance, Feret's diameter, and perimeter of the median nerve were
      calculated and compared between each position. RESULTS: Biphasic median nerve
      motion was observed, with a displacement of 2.84 +/- 3.49 mm in the ulnar
      direction from full-extension to mid-flexion (Phase I) and a further 0.93 +/-
      3.04 mm from mid-flexion to full flexion (Phase II). Of 49 hands, 37 (75.5%)
      exhibited ulnar displacement in Phase I while 12 (24.5%) exhibited radial
      displacement. Feret's diameter (5.95 +/- 1.08 mm) and perimeter (13.28 +/- 2.09)
      of the median nerve were greatest in the mid-flexed position. CONCLUSION: In a
      healthy Asian population, the median nerve has a biphasic motion during finger
      flexion, with maximal deformation in the mid-flexed position.

PMID- 25609279
TI  - Patient related functional outcome after total wrist arthroplasty: a single
      center study of 206 cases.
AB  - OBJECTIVES: To prospectively evaluate patient related outcome measures after
      total wrist arthroplasty (TWA) using four different total wrist implants operated
      at a single referral center in Sweden. METHODS: 206 primary TWAs were assessed
      preoperatively and after one year postoperatively with respect to the following
      eight outcome measures: Range of motion (flexion/extension, radial/ulnar
      deviation, pronation/supination), hand grip strength, Canadian Occupational
      Performance Measure (COPM), performance and satisfaction, Visual Analog Scale
      (VAS) pain scores at rest and in activity. RESULTS: The Maestro TWA had a
      significantly greater improvement of radial/ulnar deviation than the Biax and
      Remotion TWAs. COPM performance and satisfaction improved more for the Maestro
      and Universal 2 prostheses than the Biax and Remotion. CONCLUSIONS: All four TWAs
      offer reduced VAS-scores and improved COPM-scores with preserved hand grip
      strength and somewhat improved range of motion. The Maestro TWA performed
      favorably compared to the Remotion TWA. Implant design may affect patient related
      outcome.

PMID- 25609280
TI  - Hand and wrist injuries in professional county cricket.
AB  - AIM: This study aims to examine the mechanism and subsequent treatment modalities
      of hand and wrist injuries sustained in a professional cricket team. METHODS: We
      performed a retrospective review of prospectively collected injury data at
      Gloucestershire County Cricket Club (GCCC) over six seasons (2008-2013). We
      investigated all injuries sustained, treated by the team lead physiotherapist and
      senior author. RESULTS: There were a total of 64 injuries recorded, with 55 (86%)
      hand and 9 (14%) wrist injuries. The little and ring fingers were the most
      commonly injured, and the most commonly occurring specific injury was distal
      interphalangeal joint dislocations. The majority of injuries, 33 (52%), occurred
      during fielding activities. There were a total of 10 fractures (16%),
      predominantly phalangeal, and only 7 players (11%) had injuries that required
      operative intervention. CONCLUSIONS: The majority of injuries sustained by
      professional cricketers occur in the little and ring fingers, whilst fielding
      during match situations. We recommend buddy strapping of little and ring fingers
      during fielding to prevent injury.

PMID- 25609281
TI  - Delineation of extensor tendon of the hand by MRI: usefulness of "soap-bubble"
      mip processing technique.
AB  - To evaluate the capability of the "Soap-Bubble" maximum intensity projection
      (MIP) processing technique in visualisation of extensor tendons of the hand, 36
      intact subjects and seven patients with surgically confirmed extensor tendon
      rupture were examined. Three-dimensional T1-weighted turbo spin echo (3DT1TFE)
      MRI was performed using a sensitivity encoding flex coil, followed by Soap-Bubble
      MIP processing. For patients with extensor tendon ruptures, MRI findings and
      intraoperative findings were compared. As results, with only 3DT1TFE sequence,
      the entire extensor tendons that run along the arch of the hand were not shown on
      one image, but were visualised with addition of Soap-Bubble MIP. Although
      delineation of the extensor pollicis longus was poor in 27/43 subjects, it was
      much improved by the combination of water-suppression technique. MRI findings and
      intraoperative findings agreed in all patients. Soap-Bubble MIP processing with
      addition of water-suppression technique is considered useful for visualising the
      extensor tendons of the hand.

PMID- 25609282
TI  - Surgical outcomes of fifth metacarpal neck fractures--a comparative analysis of
      dorsal plating versus tension band wiring.
AB  - The purpose of our study is to retrospectively compare the use of tension band
      (TB) wiring and dorsal plating (DP) for the fixation of fifth metacarpal (MC)
      neck fractures. A retrospective study of patients who had surgical treatment of
      5th MC fractures from 2009 to 2013 was performed. Data including patient
      demographics, mechanism of injury, pre and postoperative pain score, range of
      motion (ROM), duration of follow-up and whether implants were removed were
      documented. Three radiological parameters: angulation (in degrees), radial-ulnar
      displacement (in millimetres) and MC height ratio were measured. There were a
      total of 84 patients with isolated closed 5th MC neck fractures, of which 41
      underwent DP and 43 underwent TB. Patients who underwent DP demonstrated better
      improvement in fracture angulation, radial-ulnar displacement, MC height ratio
      and final ROM compared to those who underwent TB. This study has shown that DP is
      a viable surgical treatment option for 5th MC neck fractures.

PMID- 25609283
TI  - Factors affecting the functional results of open reduction and internal fixation
      for fracture-dislocations of the proximal interphalangeal joint.
AB  - To clarify the factors affecting functional results of fracture-dislocations of
      the proximal interphalangeal (PIP) joint treated by open reduction and internal
      fixation (ORIF), 60 patients, including 38 patients with a dorsal fracture
      dislocation and 22 with a pilon fracture, were analysed. The mean ratio of
      articular surface involvement was 48.5% and a depressed central fragment existed
      in 75.3% of the cases. ORIF was performed in 47 patients through a lateral
      approach using Kirschner wires and in 13 through a palmar approach using a plate
      or screws. The mean flexion, extension and range of motion (ROM) of the PIP joint
      was 89.5 degrees , 11.5 degrees  and 78.0 degrees , respectively. Stepwise
      regression analysis revealed that a delayed start of active motion exercise after
      surgery, elderly age and ulnar ray digit were factors affecting functional
      outcomes. Although ORIF allows accurate restoration of the articular surfaces, an
      early start of motion exercise is essential for good results.

PMID- 25609284
TI  - Hemi-hamate arthroplasty versus transarticular Kirschner wire fixation for
      unstable dorsal fracture-dislocation of the proximal interphalangeal joint in the
      hand.
AB  - Following the introduction of the hemi-hamate arthroplasty (HHA) technique to our
      unit, we sought to evaluate the early clinical outcomes achieved with this method
      of fixation and compare these with simple trans-articular Kirschner wire (K-wire)
      fixation for dorsal fracture dislocations (DFD) of the proximal interphalangeal
      joint (PIPJ). Ninteen patients underwent fixation of these injuries with either K
      wire fixation (12/19) or hemi-hamate bone grafting (7/19) between 2005 and 2011.
      At a mean follow-up of 14 weeks median arc of movement at the PIPJ was 65 degrees
      (range 31 degrees  to 108 degrees ) following HHA and 56 degrees  (range 9
      degrees  to 85 degrees ) (p = 0.82) following temporary transarticular K-wire
      fixation. Median fixed flexion deformity (FFD) was 20 degrees  and 15 degrees 
      for hemi-hamate bone grafting and K-wire fixation respectively. Based upon our
      findings, transarticular K-wire fixation produced equivalent outcomes to HHA for
      unstable DFD of the PIPJ in the hand.

PMID- 25609285
TI  - Amniotic constriction bands: a case series and proposed new classification
      system.
AB  - INTRODUCTION: Amniotic constriction bands occur in approximately one in every
      15,000 live births and is graded using the Patterson Classification system.
      METHODS: A case series of all patients with amniotic constriction band that
      presented to Alder Hey Children's Hospital was compiled between the years 1993
      and 2012, data was described and a classification system developed. RESULTS:
      Thirty seven patients were identified. Of these 17 had amniotic constriction
      confined to the upper limbs and three of the lower limbs only. Seventeen had both
      upper and lower limb deformity. Twenty eight children underwent surgical
      intervention whilst nine to date have not. CONCLUSION: Constriction band of the
      upper limb was the most common with lower limb bands the least. There is no
      agreement on the nomenclature of this condition making amalgamation of the
      literature problematic. A more specific classification of upper limb bands has
      been suggested which includes anatomical location and depth of band.

PMID- 25609286
TI  - A retrospective review of troubled replantations.
AB  - INTRODUCTION: Replantation surgery is an established treatment for amputated
      digits, and published literature report a high success rate. However, a
      proportion of replantations do encounter postoperative problems with vascularity,
      but the incidence is unknown. Although there are studies that look at the factors
      affecting the success of replantations and the management of postoperative
      replantations, there is little literature available on this transitional period.
      We introduce the term "troubled replantation" to describe the replantation that
      manifests any form of vascular insufficiency after replantation surgery. Our
      study focuses on reviewing our centre's experience with the management and
      outcomes of troubled replantations. MATERIALS AND METHODS: Data was collected
      retrospectively from 389 digital replantations performed in our centre over an 11
      year period. We included only single level digital replantations. We analysed the
      perioperative data, and the measures taken postoperatively to promote their
      survival. RESULTS: There were a total of 137 troubled digits (35.2%). 53 digits
      responded to non-surgical measures such as dressing change and bedside bleeding
      procedures. 27 digits required re-exploration surgery, of which 16 survived. The
      majority of troubled replantations were due to arterial causes, and manifested
      signs within the first 48 h. 69 troubled digits (51%) survived. The remainder did
      not respond to any form of treatment including re-explorations and ultimately
      failed. CONCLUSION: One third of all replantations are troubled replantations,
      and half of these eventually fail despite any intervention. As troubled
      replantations can lead to postoperative failure, it is important to understand
      this clinical scenario in order to improve immediate postoperative care.

PMID- 25609287
TI  - Postoperative voluminal flap reduction after fingertip reconstruction using the
      reverse digital artery island flap.
AB  - A total of 16 fingers of 16 patients were subjected to fingertip reconstruction
      using the reverse digital artery island flap (RDAIF). We evaluated the influences
      of postoperative flap congestion, initial harvested flap size, patient's age and
      smoking habit on postoperative final flap size and postoperative range of total
      active motion (TAM) in affected fingers at a mean interval of 11.4 months. In the
      results, final flap size and TAM showed a tendency to decrease with increase in
      the initial harvested flap size and age. Eventually, the final flap size moved
      towards the size of the fingertip defect. Factors of flap congestion and smoking
      habit had little influence on the change in flap size and TAM. In conclusion,
      wide harvested flaps showed significant postoperative reduction in size compared
      with the small flaps, and extensive skin defect after flap harvest caused a
      decrease in postoperative TAM. Thus, the size of the harvested RDAIF should be
      comparable to that of the fingertip defect to prevent postoperative decrease in
      range of motion in affected fingers, and indication of this flap to the elderly
      needs to be considered. 

PMID- 25609288
TI  - A case report of acute cubital tunnel syndrome caused by venous thrombosis.
AB  - Compression neuropathy of the ulnar nerve at the elbow is well-recognised as
      cubital tunnel syndrome (CuTS). Many causes of ulnar neuropathy at the elbow have
      been identified. A previously unreported finding of ulnar nerve compression in
      the cubital tunnel caused by a thrombosed proximal ulnar recurrent artery vena
      comitans is described.

PMID- 25609289
TI  - Complete closed brachioradialis tendon rupture: a case report.
AB  - A complete brachioradialis tendon rupture, as an isolated incident, is extremely
      rare. Consequently, there is little to no literature on how this can occur and
      how to treat it. We present the case of a 44-year-old male with a complete,
      closed brachioradialis tendon rupture following a waterskiing accident. The
      clinical, imagining and operative findings are outlined alongside management and
      final outcomes. Our case highlights the effectiveness of a combined surgical and
      staged physiotherapy approach, for the management of a complete, closed
      brachioradialis tendon rupture, in an otherwise healthy man.

PMID- 25609290
TI  - Closed traumatic rupture of the flexor pollicis longus tendon in zone T I: a case
      report.
AB  - A healthy 41-year-old male suffered a direct blow on the palmar side of his right
      thumb when folding a table, which slipped along his thumb until it was stopped at
      the inter-phalangeal (IP) joint, resulting in a complete rupture of the flexor
      pollicis longus (FPL) tendon in zone T I. The proximal tendon stump was passed
      through the oblique pulley, fixed to the base of the distal phalanx with a pull
      out wire technique and augmented on it using a part of the distal tendon remnant.
      After removal of the cast and the pull-out wire three weeks postoperatively,
      range of motion exercise was initiated and good functional recovery was obtained.

PMID- 25609291
TI  - Mycobacterium chelonae infection of the hand presenting as a collar-button
      abscess.
AB  - Mycobacterial infections of the hand are extremely rare, with Mycobacterium
      chelonae being an especially uncommon source of infection. The following is a
      report of such an infection presenting as a collar-button abscess. The difficulty
      of isolating the organism, in addition to a low index of suspicion for it,
      resulted in a significant delay in appropriate treatment. The patient
      demonstrated an indolent course of infection and unresponsiveness to traditional
      treatments, both red flags that should raise concern for a mycobacterial cause.
      Eventually, repeated irrigation and debridement and a prolonged course of
      antibiotics resulted in the resolution of the patient's symptoms.

PMID- 25609292
TI  - Irreducible volar subluxation of the proximal interphalangeal joint due to radial
      collateral ligament interposition: case report and review of literature.
AB  - Irreducible volar subluxation should be considered when assessing a patient with
      flexion deformity of the proximal interphalangeal finger joint (PIPJ). Primary
      assessment requires careful examination of the collateral ligaments and extensor
      tendon. Preoperative imaging such as ultrasound and MRI can help identify the
      interposed structures and plan the subsequent operation. Although rare,
      irreducible volar subluxation due to radial collateral ligament interposition is
      an important entity to be aware of. Prompt and appropriate management can prevent
      joint stiffness and loss of function.

PMID- 25609293
TI  - A rare case of multiple subungual glomus tumours in a neurofibromatosis type 1
      patient.
AB  - Glomus tumours are uncommon lesions of the digit. They tend to be solitary. Only
      a small number of multifocal cases have been published, most of which are linked
      to an underlying genetic disorder. Here we report an unusual case of multifocal
      glomus tumours in the same hand in a patient suffering from neurofibromatosis
      type 1.

PMID- 25609294
TI  - Surgical correction of ulnar deviation deformity of the wrist in patients with
      birth brachial plexus palsy sequelae.
AB  - Ulnar deviation deformity of the wrist in patients with birth brachial plexus
      palsy is an important cosmetic concern among the patients and their relatives;
      especially in the patients who have recovered the basic limb functions. Though
      there is ample literature available regarding the management of the shoulder
      deformity there is paucity of literature regarding management of wrist ulnar
      deviation deformity. We report our experience with correction of this deformity
      in five cases with isolated ulnar deviation deformity without forearm rotational
      deformity or weakness of the wrist muscles. All the patients underwent extensor
      carpi ulnaris (ECU) to extensor carpi radialis longus (ECRL) tendon transfer. At
      a minimum of 18 months follow-up all the patients and their families were
      satisfied with the cosmetic appearance of the limb. Correction of the deformity
      improves the appearance of the limb, improves self-confidence of the child, and
      allows them to integrate well into the society. Interestingly, the patients
      expressed improvement in their grip strength and overall hand function after this
      surgery. The notable functions which improved were easy reach of the hand-to
      mouth for feeding and easy handling of the things requiring bimanual activities.
      Although the main aim of this operation was to correct the appearance of the hand
      it was found to be also functionally useful by the patients and hence we are
      encouraged to report it for wider use. The results were maintained during the
      follow-up period of as long as 47 months.

PMID- 25609295
TI  - The use of BMP-2 and screw exchange in the treatment of scaphoid fracture non
      union.
AB  - Scaphoid non-union, particularly following internal fixation, is a vexing
      problem. A retrospective review was conducted analysing the outcome of 4 patients
      who failed initial open reduction and internal fixation of scaphoid fractures.
      Three fractures were located in the waist and the fourth in the proximal pole.
      All patients underwent screw exchange and Bone Morphogenic Protein (BMP)-2 sponge
      placement with no additional bone grafting. Patients were immobilised for 4 weeks
      and followed with serial radiographs in all cases and CT scans in 3 cases. All
      patients demonstrated evidence of bony union at an average of 53 days from
      surgery and ultimately returned to pain-free full activity. There were no
      complications. BMP-2 and screw exchange yielded a 100% union rate in patients
      with established scaphoid non-union. While this retrospective study represents a
      small number of patients and clearly requires further investigation, it presents
      a promising technique for managing a difficult clinical problem. 

PMID- 25609296
TI  - New technique "graft reposition on flap" in allen type iv amputation: a report of
      six cases.
AB  - Allen type IV fingertip amputations were treated by a modified technique, when
      the replantation is difficult to be performed or not an option. The pre-existing
      technique involves nail bed grafting and local flap. In the modified technique, a
      free bone graft is added, bone and free nail bed repositioned and pulp
      reconstruction by local flap. This can be best described "graft reposition on
      flap" (GRF). GRF was found to be simple and cost effective. It allows
      preservation of finger length and a fully functional and cosmetically acceptable
      nail. 

PMID- 25609297
TI  - Total proximal interphalangeal joint arthroplasty for osteoarthritis versus
      rheumatoid arthritis--a systematic review.
AB  - Osteoarthritis (OA) and rheumatoid arthritis (RA) of the proximal interphalangeal
      joints (PIPJ) can be treated with arthroplasty, although the complicated anatomy
      of the joint makes surgery challenging. Controversy exists regarding outcomes in
      relation to disease aetiology. This study aims to compare functional outcomes and
      re-operation rates in these two conditions. The electronic databases MEDLINE,
      EMBASE, Cochrane database and Google scholar were searched in accordance with
      PRISMA. The study quality was assessed using the Methodological Index for Non
      Randomised Studies (MINOR). A total of 16 studies were reviewed including 506
      cases in the OA and 542 in the RA group. Five studies assessed function and
      patient satisfaction, demonstrating a non-significant improvement in the OA
      group. Five studies reported re-operation rate; three showing it to be lower in
      the OA group and two reporting similar rates. This review suggests that those
      undergoing PIPJ arthroplasty for OA may have a better functional outcome and
      lower re-operation rate.

PMID- 25609298
TI  - Current management of hand enchondroma: a review.
AB  - Enchondromas are benign bone tumours originating from cartilages. It is mainly
      discovered incidentally in radiographs or due to symptoms like pathological
      fracture or pain. Conservative treatment through regular check-up and surgical
      excision using curettage are the two major treatment methods for enchondromas.
      This review concludes that small localized asymptomatic lesions can be treated
      conservatively while most expanding or symptomatic lesions should be treated with
      simple curettage. Adjuvant treatments like high-speed burring or alcohol
      instillation are not recommended.

PMID- 25609299
TI  - Improved communication of complications during the consent process in hand
      surgery.

PMID- 25609300
TI  - The chicken foot digital replant training model.
AB  - A simple, readily available digital replantation model in the chicken foot is
      described. This high fidelity model will hopefully allow trainees in hand surgery
      to gain further experience in replant surgery prior to clinical application. 

PMID- 25609301
TI  - Erratum: "anatomy of the extensor pollicis brevis associated with an extension
      mechanism of the thumb metacarpophalangeal joint".

PMID- 25609304
TI  - History and current status of development and use of viral insecticides in China.
AB  - The use of insect viruses as biological control agents started in the early 1960s
      in China. To date, more than 32 viruses have been used to control insect pests in
      agriculture, forestry, pastures, and domestic gardens in China. In 2014, 57
      products from 11 viruses were authorized as commercial viral insecticides by the
      Ministry of Agriculture of China. Approximately 1600 tons of viral insecticidal
      formulations have been produced annually in recent years, accounting for about
      0.2% of the total insecticide output of China. The development and use of
      Helicoverpa armigera nucleopolyhedrovirus, Mamestra brassicae
      nucleopolyhedrovirus, Spodoptera litura nucleopolyhedrovirus, and Periplaneta
      fuliginosa densovirus are discussed as case studies. Additionally, some
      baculoviruses have been genetically modified to improve their killing rate,
      infectivity, and ultraviolet resistance. In this context, the biosafety
      assessment of a genetically modified Helicoverpa armigera nucleopolyhedrovirus is
      discussed. 

PMID- 25609303
TI  - Modeling of the Ebola virus delta peptide reveals a potential lytic sequence
      motif.
AB  - Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human
      infection, including the extensive epidemic of Ebola virus disease (EVD) in West
      Africa in 2014. In the course of examining mutations in the glycoprotein gene
      associated with 2014 Ebola virus (EBOV) sequences, a differential level of
      conservation was noted between the soluble form of glycoprotein (sGP) and the
      full length glycoprotein (GP), which are both encoded by the GP gene via RNA
      editing. In the region of the proteins encoded after the RNA editing site sGP was
      more conserved than the overlapping region of GP when compared to a distant
      outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the
      "delta peptide", a 40 amino acid carboxy-terminal fragment of sGP, were identical
      between otherwise widely divergent species. A lysine-rich amphipathic peptide
      motif was noted at the carboxyl terminus of delta peptide with high structural
      relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of
      rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming
      peptide, and may contribute to EBOV pathogenesis. 

PMID- 25609305
TI  - ERVK polyprotein processing and reverse transcriptase expression in human cell
      line models of neurological disease.
AB  - Enhanced expression of the reverse transcriptase (RT) protein encoded by human
      endogenous retrovirus-K (ERVK) is a promising biomarker for several inflammatory
      and neurological diseases. However, unlike RT enzymes encoded by exogenous
      retroviruses, little work has been done to identify ERVK RT isoforms, their
      expression patterns, and cellular localization. Using Western blot, we showcase
      the ERVK gag-pro-pol polyprotein processing leading to the production of several
      ERVK RT isoforms in human neuronal (ReNcell CX) and astrocytic (SVGA) models of
      neuroinflammatory disease. Since the pro-inflammatory cytokine IFNgamma plays a
      key role in the pathology of several ERVK-associated neurological diseases, we
      sought to determine if IFNgamma can drive ERVK RT expression. IFNgamma signalling
      markedly enhanced ERVK polyprotein and RT expression in both human astrocytes and
      neurons. RT isoforms were expressed in a cell-type specific pattern and the RT
      RNase H form was significantly increased with IFNgamma treatment. Fluorescent
      imaging revealed distinct cytoplasmic, perinuclear and nuclear ERVK RT staining
      patterns upon IFNgamma stimulation of astrocytes and neurons. These findings
      indicate that ERVK expression is inducible under inflammatory conditions such as
      IFNgamma exposure-and thus, these newly established in vitro models may be useful
      in exploring ERVK biology in the context of neuroinflammatory disease. 

PMID- 25609306
TI  - The association between hantavirus infection and selenium deficiency in mainland
      China.
AB  - Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and
      transmitted by rodents is a significant public health problem in China, and
      occurs more frequently in selenium-deficient regions. To study the role of
      selenium concentration in HFRS incidence we used a multidisciplinary approach
      combining ecological analysis with preliminary experimental data. The incidence
      of HFRS in humans was about six times higher in severe selenium-deficient and
      double in moderate deficient areas compared to non-deficient areas. This
      association became statistically stronger after correction for other significant
      environment-related factors (low elevation, few grasslands, or an abundance of
      forests) and was independent of geographical scale by separate analyses for
      different climate regions. A case-control study of HFRS patients admitted to the
      hospital revealed increased activity and plasma levels of selenium binding
      proteins while selenium supplementation in vitro decreased viral replication in
      an endothelial cell model after infection with a low multiplicity of infection
      (MOI). Viral replication with a higher MOI was not affected by selenium
      supplementation. Our findings indicate that selenium deficiency may contribute to
      an increased prevalence of hantavirus infections in both humans and rodents.
      Future studies are needed to further examine the exact mechanism behind this
      observation before selenium supplementation in deficient areas could be
      implemented for HFRS prevention. 

PMID- 25609308
TI  - Viral etiologies of acute dehydrating gastroenteritis in pakistani children:
      confounding role of parechoviruses.
AB  - Despite substantial interventions in the understanding and case management of
      acute gastroenteritis, diarrheal diseases are still responsible for a notable
      amount of childhood deaths. Although the rotavirus is known to cause a
      considerable burden of pediatric diarrheal cases, the roles of other viruses
      remain undefined for the Pakistani population. This study was based on tertiary
      care hospital surveillance, from January 2009 to December 2010, including the
      detection of rotavirus, norovirus, astrovirus, and human parechovirus in children
      under the age of five using serological or molecular assays. Rotavirus, human
      parechovirus, norovirus, and astrovirus were detected in 66%, 21%, 19.5%, and
      8.5% subjects, respectively. Human parechovirus genotypes, determined through
      analysis of VP1 gene sequences, showed a great diversity among co-circulating
      strains. Eighty percent of hospitalized children had dual or multiple viral
      infections, while 98% parechovirus positive cases were co-infected with
      rotavirus. The remarkable diversity of viruses associated with the childhood
      diarrhea in Pakistan calls for large-scale epidemiological surveys, coupled with
      case control studies, to ascertain their role in clinical manifestations. In
      addition, these findings also highlight the need for the implementation of up-to
      date health interventions, such as the inclusion of a rotavirus vaccine in
      routine immunization programs for the improvement of quality in child health
      care. 

PMID- 25609307
TI  - Epimedium koreanum Nakai displays broad spectrum of antiviral activity in vitro
      and in vivo by inducing cellular antiviral state.
AB  - Epimedium koreanum Nakai has been extensively used in traditional Korean and
      Chinese medicine to treat a variety of diseases. Despite the plant's known immune
      modulatory potential and chemical make-up, scientific information on its
      antiviral properties and mode of action have not been completely investigated. In
      this study, the broad antiviral spectrum and mode of action of an aqueous extract
      from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the
      protective effect against divergent influenza A subtypes was determined in BALB/c
      mice. An effective dose of Epimedium koreanum Nakai markedly reduced the
      replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes
      Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T
      cells. Mechanically, we found that an aqueous extract from Epimedium koreanum
      Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the
      subsequent stimulation of the antiviral state in cells. Among various components
      present in the extract, quercetin was confirmed to have striking antiviral
      properties. The oral administration of Epimedium koreanum Nakai exhibited
      preventive effects on BALB/c mice against lethal doses of highly pathogenic
      influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of
      Epimedium koreanum Nakai and its components play roles as immunomodulators in the
      innate immune response, and may be potential candidates for prophylactic or
      therapeutic treatments against diverse viruses in animal and humans. 

PMID- 25609309
TI  - The complete sequence of the first Spodoptera frugiperda Betabaculovirus genome:
      a natural multiple recombinant virus.
AB  - Spodoptera frugiperda (Lepidoptera: Noctuidae) is a major pest in maize crops in
      Colombia, and affects several regions in America. A granulovirus isolated from S.
      frugiperda (SfGV VG008) has potential as an enhancer of insecticidal activity of
      previously described nucleopolyhedrovirus from the same insect species (SfMNPV).
      The SfGV VG008 genome was sequenced and analyzed showing circular double stranded
      DNA of 140,913 bp encoding 146 putative ORFs that include 37 Baculoviridae core
      genes, 88 shared with betabaculoviruses, two shared only with betabaculoviruses
      from Noctuide insects, two shared with alphabaculoviruses, three copies of own
      genes (paralogs) and the other 14 corresponding to unique genes without
      representation in the other baculovirus species. Particularly, the genome encodes
      for important virulence factors such as 4 chitinases and 2 enhancins. The
      sequence analysis revealed the existence of eight homologous regions (hrs) and
      also suggests processes of gene acquisition by horizontal transfer including the
      SfGV VG008 ORFs 046/047 (paralogs), 059, 089 and 099. The bioinformatics evidence
      indicates that the genome donors of mentioned genes could be alpha- and/or
      betabaculovirus species. The previous reported ability of SfGV VG008 to naturally
      co-infect the same host with other virus show a possible mechanism to capture
      genes and thus improve its fitness. 

PMID- 25609310
TI  - Expression, delivery and function of insecticidal proteins expressed by
      recombinant baculoviruses.
AB  - Since the development of methods for inserting and expressing genes in
      baculoviruses, a line of research has focused on developing recombinant
      baculoviruses that express insecticidal peptides and proteins. These recombinant
      viruses have been engineered with the goal of improving their pesticidal
      potential by shortening the time required for infection to kill or incapacitate
      insect pests and reducing the quantity of crop damage as a consequence. A wide
      variety of neurotoxic peptides, proteins that regulate insect physiology,
      degradative enzymes, and other potentially insecticidal proteins have been
      evaluated for their capacity to reduce the survival time of baculovirus-infected
      lepidopteran host larvae. Researchers have investigated the factors involved in
      the efficient expression and delivery of baculovirus-encoded insecticidal
      peptides and proteins, with much effort dedicated to identifying ideal promoters
      for driving transcription and signal peptides that mediate secretion of the
      expressed target protein. Other factors, particularly translational efficiency of
      transcripts derived from recombinant insecticidal genes and post-translational
      folding and processing of insecticidal proteins, remain relatively unexplored.
      The discovery of RNA interference as a gene-specific regulation mechanism offers
      a new approach for improvement of baculovirus biopesticidal efficacy through
      genetic modification. 

PMID- 25609311
TI  - Integrated transcriptome catalogue and organ-specific profiling of gene
      expression in fertile garlic (Allium sativum L.).
AB  - BACKGROUND: Garlic is cultivated and consumed worldwide as a popular condiment
      and green vegetable with medicinal and neutraceutical properties. Garlic
      cultivars do not produce seeds, and therefore, this plant has not been the
      subject of either classical breeding or genetic studies. However, recent
      achievements in fertility restoration in a number of genotypes have led to
      flowering and seed production, thus enabling genetic studies and breeding in
      garlic. RESULTS: A transcriptome catalogue of fertile garlic was produced from
      multiplexed gene libraries, using RNA collected from various plant organs,
      including inflorescences and flowers. Over 32 million 250-bp paired-end reads
      were assembled into an extensive transcriptome of 240,000 contigs. An abundant
      transcriptome assembled separately from 102,000 highly expressed contigs was
      annotated and analyzed for gene ontology and metabolic pathways. Organ-specific
      analysis showed significant variation of gene expression between plant organs,
      with the highest number of specific reads in inflorescences and flowers. Analysis
      of the enriched biological processes and molecular functions revealed
      characteristic patterns for stress response, flower development and
      photosynthetic activity. Orthologues of key flowering genes were differentially
      expressed, not only in reproductive tissues, but also in leaves and bulbs,
      suggesting their role in flower-signal transduction and the bulbing process. More
      than 100 variants and isoforms of enzymes involved in organosulfur metabolism
      were differentially expressed and had organ-specific patterns. In addition to
      plant genes, viral RNA of at least four garlic viruses was detected, mostly in
      the roots and cloves, whereas only 1-4% of the reads were found in the foliage
      leaves. CONCLUSIONS: The de novo transcriptome of fertile garlic represents a new
      resource for research and breeding of this important crop, as well as for the
      development of effective molecular markers for useful traits, including fertility
      and seed production, resistance to pests and neutraceutical characteristics.

PMID- 25609312
TI  - The Hd, Hj, and Hz66 flagella variants of Salmonella enterica serovar Typhi
      modify host responses and cellular interactions.
AB  - Salmonella Typhi, the causative agent of typhoid fever, is a monophyletic, human
      restricted bacterium that exhibits limited phenotypic variation. S. Typhi from
      Indonesia are a notable exception, with circulating strains expressing diverse
      flagella antigens including Hj, Hd and Hz66. Hypothesizing that S. Typhi flagella
      plays a key role during infection, we constructed an S. Typhi fliC mutant and
      otherwise isogenic S. Typhi strains expressing the Hj, Hd, Hz66 flagella
      antigens. Phenotyping revealed differences in flagellum structure, strain
      motility and immunogenicity, but not in the ability of flagellated isolates to
      induce TLR5 activity. Invasion assays using epithelial and macrophage cell lines
      revealed differences in the ability of these S. Typhi derivatives to invade cells
      or induce cellular restructuring in the form of ruffles. Notably, the Hj variant
      induced substantial ruffles that were not fully dependent on the GTPases that
      contribute to this process. These data highlight important differences in the
      phenotypic properties of S. Typhi flagella variation and how they impact on the
      pathogenesis of S. Typhi. 

PMID- 25609313
TI  - Prognostic value of volumetric metabolic parameters measured by
      [18F]fluorodeoxyglucose-positron emission tomography/computed tomography in
      patients with small cell lung cancer.
AB  - BACKGROUND: We evaluated the prognostic value of volume-based metabolic positron
      emission tomography (PET) parameters in patients with small cell lung cancer
      (SCLC) compared with other factors. METHODS: The subjects were 202 patients with
      pathologically proven SCLC who underwent pretreatment 18F-fluorodeoxyglucose
      (FDG) PET/computed tomography (CT). Volumetric metabolic parameters of
      intrathoracic malignant hypermetabolic lesions, including maximum and average
      standardized uptake value, sum of metabolic tumor volume (MTV), and sum of total
      lesion glycolysis (TLG) were measured. RESULTS: 164 patients had died during
      follow-up (median 17.4 months) and median overall survival was 14 months. On
      univariate survival analysis, age, stage, treatment modality, sum of MTV (cutoff
      = 100 cm3), and sum of TLG (cutoff = 555) were significant predictors of
      survival. There was a very high correlation between the sum of MTV and the sum of
      TLG (r = 0.963, P < 0.001). On multivariate survival analysis, age (HR = 1.04, P
      < 0.001), stage (HR = 2.442, P < 0.001), and sum of MTV (HR = 1.662, P = 0.002)
      were independent prognostic factors. On subgroup analysis based on limited
      disease (LD) and extensive disease (ED), sum of MTV and sum of TLG were
      significant prognostic factors only in LD. CONCLUSION: Both sum of MTV and sum of
      TLG of intrathoracic malignant hypermetabolic lesions are important independent
      prognostic factors for survival in patients with SCLC, in addition to age and
      clinical stage. However, it may be more useful in limited disease rather than in
      extensive disease.

PMID- 25609314
TI  - Distinguishing proteins from arbitrary amino acid sequences.
AB  - What kinds of amino acid sequences could possibly be protein sequences? From all
      existing databases that we can find, known proteins are only a small fraction of
      all possible combinations of amino acids. Beginning with Sanger's first detailed
      determination of a protein sequence in 1952, previous studies have focused on
      describing the structure of existing protein sequences in order to construct the
      protein universe. No one, however, has developed a criteria for determining
      whether an arbitrary amino acid sequence can be a protein. Here we show that when
      the collection of arbitrary amino acid sequences is viewed in an appropriate
      geometric context, the protein sequences cluster together. This leads to a new
      computational test, described here, that has proved to be remarkably accurate at
      determining whether an arbitrary amino acid sequence can be a protein. Even more,
      if the results of this test indicate that the sequence can be a protein, and it
      is indeed a protein sequence, then its identity as a protein sequence is uniquely
      defined. We anticipate our computational test will be useful for those who are
      attempting to complete the job of discovering all proteins, or constructing the
      protein universe. 

PMID- 25609315
TI  - Complementary medicine centres should be more critical, says Ernst.

PMID- 25609316
TI  - Does single port improve results of laparoscopic colorectal surgery? A propensity
      score adjustment analysis.
AB  - BACKGROUND: The benefit of single-incision laparoscopy (SIL) over conventional
      multiport laparoscopy (ML) is not demonstrated in colorectal surgery, mainly
      because of potentially biased reports. The objective of this study was to compare
      SIL to ML for colorectal resection, using a propensity score (PS) adjusted
      analysis. METHODS: From July 2009 to April 2013, 764 patients who underwent 799
      colorectal resections by SIL or ML were analyzed. PS was estimated using a
      logistic regression model. RESULTS: Eighty-four colorectal resections were
      performed using SIL: 43 ileocolic resections, 15 right-sided colectomies, 14 left
      sided colectomies, 5 rectal resections, 4 subtotal colectomies, and 3 total
      proctocolectomies. Intra-operative complications occurred in 3 procedures (4 %),
      and conversion laparotomy in 10 (12 %). Postoperative mortality was nil and
      overall morbidity rate was 25 %, including 7 % of major complications. Mean
      postoperative length of hospital stay was 8 +/- 6 (4-47) days. Outcomes of SIL,
      when compared to those of 715 ML and after PS adjustment, showed no difference in
      terms of intra-operative complication (p = 0.315), conversion to open surgery (p
      = 0.387), overall morbidity (p = 0.393), major morbidity (p = 0.381), or length
      of postoperative hospital stay (p = 0.080). However, the length of hospital stay
      was significantly shorter after SIL in the right colectomy subgroup (p = 0.001).
      CONCLUSIONS: In colorectal surgery, SIL appears to be safe and effective as
      compared to ML. It can also reduce hospital stay after right colectomy. These
      results, if confirmed by randomized trials, would validate SIL in colorectal
      surgery.

PMID- 25609318
TI  - External validation of Global Evaluative Assessment of Robotic Skills (GEARS).
AB  - BACKGROUND: We demonstrate the construct validity, reliability, and utility of
      Global Evaluative Assessment of Robotic Skills (GEARS), a clinical assessment
      tool designed to measure robotic technical skills, in an independent cohort using
      an in vivo animal training model. METHODS: Using a cross-sectional observational
      study design, 47 voluntary participants were categorized as experts (>30 robotic
      cases completed as primary surgeon) or trainees. The trainee group was further
      divided into intermediates (>=5 but <=30 cases) or novices (<5 cases). All
      participants completed a standardized in vivo robotic task in a porcine model.
      Task performance was evaluated by two expert robotic surgeons and self-assessed
      by the participants using the GEARS assessment tool. Kruskal-Wallis test was used
      to compare the GEARS performance scores to determine construct validity;
      Spearman's rank correlation measured interobserver reliability; and Cronbach's
      alpha was used to assess internal consistency. RESULTS: Performance evaluations
      were completed on nine experts and 38 trainees (14 intermediate, 24 novice).
      Experts demonstrated superior performance compared to intermediates and novices
      overall and in all individual domains (p < 0.0001). In comparing intermediates
      and novices, the overall performance difference trended toward significance (p =
      0.0505), while the individual domains of efficiency and autonomy were
      significantly different between groups (p = 0.0280 and 0.0425, respectively).
      Interobserver reliability between expert ratings was confirmed with a strong
      correlation observed (r = 0.857, 95 % CI [0.691, 0.941]). Experts and participant
      scoring showed less agreement (r = 0.435, 95 % CI [0.121, 0.689] and r = 0.422,
      95 % CI [0.081, 0.0672]). Internal consistency was excellent for experts and
      participants (alpha = 0.96, 0.98, 0.93). CONCLUSIONS: In an independent cohort,
      GEARS was able to differentiate between different robotic skill levels,
      demonstrating excellent construct validity. As a standardized assessment tool,
      GEARS maintained consistency and reliability for an in vivo robotic surgical task
      and may be applied for skills evaluation in a broad range of robotic procedures.

PMID- 25609319
TI  - Effects of preoperative carbohydrates drinks on immediate postoperative outcome
      after day care laparoscopic cholecystectomy.
AB  - BACKGROUND: Postoperative nausea and vomiting is the most common cause for
      unexpected hospital admission of patients undergoing day care surgery. Overnight
      fasting changes patient metabolic state and influences their perioperative stress
      response. Preoperative carbohydrate loading may have accelerated recovery and
      better overall outcome after major abdominal surgery. The aim of the study was to
      investigate the effects of preoperative carbohydrate-rich drinks on postoperative
      nausea and vomiting and pain after day care laparoscopic cholecystectomy.
      METHODS: A total of 120 patients posted for day care laparoscopic cholecystectomy
      were included in the study and were randomized into three groups. Group A (Cases)
      receiving the carbohydrate-rich drink before surgery (CHO), group B (placebo)
      receiving the placebo drink before surgery and group C (controls)-fasting from
      midnight before surgery. Postoperative nausea and vomiting and visual analogue
      score for pain were noted and analyzed for 24 h. RESULTS: Mean score of nausea in
      0-4 h in group A was significantly lower as compared to group B and group C (p =
      0.001). Difference in mean score of nausea in 4-12 and 12-24 h between groups was
      not significant (p = 0.066), (p = 0.257). Mean score of vomiting in 0-4 and 4-12
      h in group A was significantly less than that of group B and group C (p = 0.004),
      (p = 0.001). Mean score of pain in group A was significantly less when compared
      to group B and group C in 0-4 h (p = 0.001) and 4-12 h (0.005). CONCLUSION:
      Perioperative consumption of a carbohydrate-rich drink can minimize postoperative
      nausea, vomiting and pain in patients undergoing outpatient cholecystectomy.
      Consumption of carbohydrate drinks up to 2 h prior to surgery is not associated
      with additional complications.

PMID- 25609317
TI  - Early rectal cancer: the European Association for Endoscopic Surgery (EAES)
      clinical consensus conference.
AB  - BACKGROUND: The last 30 years have witnessed a significant increase in the
      diagnosis of early-stage rectal cancer and the development of new strategies to
      reduce the treatment-related morbidity. Currently, there is no consensus on the
      definition of early rectal cancer (ERC), and the best management of ERC has not
      been yet defined. The European Association for Endoscopic Surgery in
      collaboration with the European Society of Coloproctology developed this
      consensus conference to provide recommendations on ERC diagnosis, staging and
      treatment based on the available evidence. METHODS: A multidisciplinary group of
      experts selected on their clinical and scientific expertise was invited to
      critically review the literature and to formulate evidence-based recommendations
      by the Delphi method. Recommendations were discussed at the plenary session of
      the 14th World Congress of Endoscopic Surgery, Paris, 26 June 2014, and then
      posted on the EAES website for open discussion. RESULTS: Tumour biopsy has a low
      accuracy. Digital rectal examination plays a key role in the pre-operative work
      up. Magnification chromoendoscopy, endoscopic ultrasound and magnetic resonance
      imaging are complementary staging modalities. Endoscopic submucosal dissection
      and transanal endoscopic microsurgery are the two established approaches for
      local excision (LE) of selected ERC. The role of all organ-sparing approaches
      including neoadjuvant therapies followed by LE should be formally assessed by
      randomized controlled trials. Rectal resection and total mesorectal excision is
      indicated in the presence of unfavourable features at the pathological evaluation
      of the LE specimen. The laparoscopic approach has better short-term outcomes and
      similar oncologic results when compared with open surgery. CONCLUSIONS: The
      management of ERC should always be based on a multidisciplinary approach, aiming
      to increase the rate of organ-preserving procedures without jeopardizing
      survival.

PMID- 25609321
TI  - Significance of large local reactions that occur during allergen immunotherapy.

PMID- 25609320
TI  - The efficacy and safety of once-daily quetiapine extended release in patients
      with schizophrenia switched from other antipsychotics: an open-label study in
      Chinese population.
AB  - BACKGROUND: Non-adherence to antipsychotic medication in schizophrenic patients
      is common and associated with symptom relapse and poorer long-term outcomes. The
      risk factors for treatment non-adherence include dosing frequency and complexity.
      Besides, slower dose titration in an acute schizophrenic episode may lead to
      attenuated efficacy. Therefore, the convenient dosage regimen and rapid
      initiation scheme of quetiapine extended release (XR) were expected to provide
      better effectiveness and promote adherence in patients with schizophrenia. This
      study was implemented to assess the efficacy and safety of once-daily quetiapine
      XR in schizophrenic patients with switched from other antipsychotics which were
      suboptimal due to insufficient efficacy or tolerability. METHODS: This was a 12
      week, open-label study conducted in the Chinese population in Taiwan. Patients
      who had a score of 4 (moderate) or greater on any of the 7 items of the Positive
      and Negative Syndrome Scale (PANSS) Positive Symptom Subscale and needed to
      switch from previous antipsychotics were recruited. Quetiapine XR was
      administered at 300 mg on day 1, 600 mg on day 2 and up to 800 mg after day 2.
      From day 8 until the end of the study, the dose of quetiapine XR was adjusted
      within 400-800 mg per day, depending on the clinical response and tolerance of
      the patients. The variable of the primary outcome was the change from baseline to
      Week 12 in PANSS total and subscale scores. Secondary outcome was the baseline-to
      endpoint difference in the Clinical Global Impression-Severity (CGI-S) scores of
      the participants. RESULTS: Sixty-one patients were recruited and 55.7% of them
      completed the study. The mean changes in the PANSS total score and CGI-S score
      showed significant improvement (-18.4, p < .001 and -1.0, p < .001,
      respectively). Four patients (6.7%) experienced adverse events including
      headache, exacerbation of psychosis and dysuria. The use of concomitant
      anticholinergics decreased from 15.0% to 8.3%. CONCLUSIONS: The results of our
      investigation implicated that quetiapine XR was an effective and well tolerated
      alternative for Chinese schizophrenic patients with previous suboptimal
      treatment. Future large-scale studies are warranted to validate our results.
      TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02142556 . Registered 15 May 2014.

PMID- 25609322
TI  - Diagnosing exercise-induced bronchoconstriction with eucapnic voluntary
      hyperpnea: is one test enough?
AB  - BACKGROUND: In athletic individuals, a secure diagnosis of exercise-induced
      bronchoconstriction (EIB) is dependent on objective testing. Indirect
      bronchoprovocation testing is often used in this context and eucapnic voluntary
      hyperpnea (EVH) testing is recommended for this purpose, yet the short-term
      reproducibility of EVH is yet to be appropriately established. OBJECTIVE: The aim
      of this study was to evaluate the reproducibility of EVH in a cohort of
      recreational athletes. METHODS: A cohort of recreational athletes (n = 32)
      attended the laboratory on two occasions to complete an EVH challenge, separated
      by a period of 14 or 21 days. Spirometry and impulse oscillometry was performed
      before and after EVH. Training load was maintained between visits. RESULTS:
      Prechallenge lung function was similar at both visits (P > .05). No significant
      difference was observed in maximum change in FEV1 (DeltaFEV1max) after EVH
      between visits (P > .05), and test-retest DeltaFEV1max was correlated (intraclass
      correlation coefficient = 0.81; r(2) = 0.66; P = .001). Poor diagnostic
      reliability was observed between tests; 11 athletes were diagnosed with EIB (on
      the basis of DeltaFEV1max >=10%) at visit 1 and at visit 2. However, only 7
      athletes were positive at both visits. Although there was a small mean difference
      in DeltaFEV1max between tests (-0.6%), there were wide limits of agreement (
      10.7% to 9.5%). Likewise, similar results were observed for impulse oscillometry
      between visits. CONCLUSIONS: In a cohort of recreational athletes, EVH
      demonstrated poor clinical reproducibility for the diagnosis of EIB. These
      findings highlight a need for caution when confirming or refuting EIB on the
      basis of a single indirect bronchoprovocation challenge. When encountering
      patients with mild or borderline EIB, we recommend that more than one EVH test is
      performed to exclude or confirm a diagnosis.

PMID- 25609323
TI  - Serum IL-12 and soluble IL-2 receptor levels as possible biomarkers of
      granulomatous and lymphocytic interstitial lung disease in common variable
      immunodeficiency: a case report.

PMID- 25609324
TI  - Development and internal validation of a pediatric acute asthma prediction rule
      for hospitalization.
AB  - BACKGROUND: Clinicians have difficulty predicting need for hospitalization of
      children with acute asthma exacerbations. OBJECTIVE: The objective of this study
      was to develop and internally validate a multivariable asthma prediction rule
      (APR) to inform hospitalization decision making in children aged 5-17 years with
      acute asthma exacerbations. METHODS: Between April 2008 and February 2013 we
      enrolled a prospective cohort of patients aged 5-17 years with asthma who
      presented to our pediatric emergency department with acute exacerbations.
      Predictors for APR modeling included 15 demographic characteristics, asthma
      chronic control measures, and pulmonary examination findings in participants at
      the time of triage and before treatment. The primary outcome variable for APR
      modeling was need for hospitalization (length of stay >24 h for those admitted to
      hospital or relapse for those discharged). A secondary outcome was the
      hospitalization decision of the clinical team. We used penalized maximum
      likelihood multiple logistic regression modeling to examine the adjusted
      association of each predictor variable with the outcome. Backward step-down
      variable selection techniques were used to yield reduced-form models. RESULTS:
      Data from 928 of 933 participants were used for prediction rule modeling, with
      median [interquartile range] age 8.8 [6.9, 11.2] years, 61% male, and 59% African
      American race. Both full (penalized) and reduced-form models for each outcome
      calibrated well, with bootstrap-corrected c-indices of 0.74 and 0.73 for need for
      hospitalization and 0.81 in each case for hospitalization decision. CONCLUSION:
      The APR predicts the need for hospitalization of children with acute asthma
      exacerbations using predictor variables available at the time of presentation to
      an emergency department.

PMID- 25609326
TI  - Network meta-analysis shows commercialized subcutaneous and sublingual grass
      products have comparable efficacy.
AB  - BACKGROUND: Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT)
      have been shown to effectively treat grass pollen allergies, although direct
      comparisons are sparse. OBJECTIVE: To estimate the relative efficacy of SLIT
      tablets compared with SCIT and SLIT drops in commercially available products
      though network meta-analysis. METHODS: A literature search of MEDLINE, Embase,
      and Cochrane Library publications. Randomized, double-blind clinical trials of
      SCIT, SLIT drops, and SLIT tablets for grass pollen were included. Bayesian
      network meta-analyses estimated the standardized mean difference (SMD) across 3
      immunotherapy modalities on allergic rhinoconjunctivitis symptom and medication
      score data from publications or received from authors. Both fixed and random
      effects models were investigated. RESULTS: Thirty-seven studies were included in
      meta-analyses for symptom scores and 31 studies for medication scores. In the
      random effects model, SCIT and SLIT tablets were significantly different from
      placebo for symptom scores: SMDs (95% CI) of -0.32 (-0.45 to -0.18) and -0.32 (
      0.41 to -0.23), respectively. No significant difference was identified for SLIT
      drops compared with placebo (SMD, -0.17; -0.37 to 0.04). For medication scores,
      significant differences compared with placebo were observed for SCIT (SMD, -0.33;
      95% CI, -0.52 to -0.13), SLIT tablets (SMD, -0.23; 95% CI, -0.29 to -0.17), and
      SLIT drops (SMD, -0.44; 95% CI, -0.83 to -0.06). Network meta-analysis revealed
      no significant differences in SMDs (95% credible interval) for symptom scores
      (0.0145 [-0.19 to 0.23]) or medication scores (0.133 [-0.31 to 0.57]) between
      SLIT tablets and SCIT, or for symptom scores (-0.175 [-0.37 to 0.02]) and
      medication scores (0.188 [-0.18 to 0.56]) between SLIT tablets and SLIT drops.
      CONCLUSIONS: The comparisons for grass pollen immunotherapy products
      commercialized in at least 1 country indicate comparable reductions in allergic
      rhinoconjunctivitis symptoms and supplemental medication use for SLIT tablets and
      SCIT in the first pollen season.

PMID- 25609327
TI  - Successful stem cell transplantation in Chediak-Higashi syndrome.

PMID- 25609325
TI  - Clinical characteristics of adults with chronic rhinosinusitis and specific
      antibody deficiency.
AB  - BACKGROUND: Specific antibody deficiency (SAD) involves a deficient response to a
      polysaccharide vaccine in the setting of normal immunoglobulin G (IgG) levels and
      chronic infections. Patients with chronic rhinosinusitis (CRS) are often
      evaluated for SAD. There are limited data that describe patients with CRS and
      SAD. OBJECTIVE: The objective of this study was to better characterize the role
      of SAD in CRS. METHODS: We reviewed electronic records of adults with CRS who
      were evaluated for immunodeficiency with quantitative Ig levels and pre- and
      postantibody titers to a pneumococcal polysaccharide vaccine (PPV). RESULTS:
      Fourteen pneumococcal serotypes were determined in 239 subjects from 2002 to
      2009. Of these subjects, 64 had adequate protective titers of 1.3 MUg/mL or
      higher in 7 or more serotypes of the 14 serotypes checked; 56 (23%) had less than
      7 protective titers post-PPV and were diagnosed with SAD; and 119 had an adequate
      response to the vaccine with 7 or more serotypes being higher than 1.3 MUg/mL
      (>50% response) and were characterized as "responders." Subjects with SAD
      received more antibiotic courses relative to responders in the 2 years after
      immunization (3.19 +/- 2.64 vs 2.19 +/- 2.24, P < .05). Of 56 subjects with SAD,
      10 (17.9%) received Ig replacement therapy. Subjects who received Ig had fewer
      numbers of protective pneumococcal titers post-PPV and had more pneumonia (40.0%)
      versus subjects with SAD who did not receive Ig (10.9%). CONCLUSIONS: Of the 239
      patients with CRS with normal IgG levels evaluated for immunodeficiency, 56
      (23.4%) had SAD. A majority of patients with SAD may not need Ig replacement;
      however, a subset of patients with SAD benefit from Ig replacement.

PMID- 25609328
TI  - Current medical management of hereditary angioedema: follow-up survey of US
      physicians.
AB  - BACKGROUND: A physician survey conducted in the United States between October
      2009 and February 2010 revealed wide variability in hereditary angioedema (HAE)
      management. OBJECTIVE: A follow-up survey was conducted to assess the impact of
      newly available treatment options and investigate changes in HAE care patterns.
      METHODS: Between March and June 2013, 6570 physicians were contacted, of whom,
      245 HAE-treating physicians responded. Participants completed a 46-question
      online survey that was closely patterned after the initial survey. Although most
      data were analyzed descriptively, selected questions underwent statistical
      analysis to evaluate differences in treatment patterns between the 2 surveys.
      RESULTS: Compared with the prior survey, this follow-up survey found that the
      proportion of physicians who reported danazol as the preferred long-term
      prophylaxis agent declined from 56% to 23% (P < .00005); conversely, C1-esterase
      inhibitor increased in this category (20% to 57%; P < .00005). The percentage of
      attacks self-treated at home increased from 8% to 27% (P < .00005). Decreases
      were observed in emergency department visits (61% to 54%; P = not significant)
      and hospitalizations (13% to 3%; P = .0001) for HAE attacks. The percentage of
      patients perceived by physicians to be very satisfied with HAE treatment
      increased from 13% to 40% (P < .00005). In 2013, convenience was reported more
      frequently as an important patient factor that drove long-term prophylaxis choice
      (27% vs 10%; P < .00005), whereas adverse effects were cited less frequently (16%
      vs 42%; P < .00005); in both surveys, cost and/or insurance coverage was the
      greatest driver in this category (43% and 46%). CONCLUSION: Analysis of these
      findings suggests that the change in HAE treatment has increased self-treatment
      at home, decreased emergency department visits and/or hospitalizations, and
      provided greater patient satisfaction.

PMID- 25609330
TI  - The uses of telemedicine to improve asthma control.

PMID- 25609329
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional
      analysis of patients in an integrated allergy repository of a large health care
      system.

PMID- 25609331
TI  - Evaluation and subsequent safe administration of rabies vaccine to a child
      presumably allergic to the gelatin content of PCECV Rabavert.

PMID- 25609332
TI  - A Pitfall to Avoid When Using an Allergen Microarray: The Incidental Detection of
      IgE to Unexpected Allergens.
AB  - The introduction of new laboratory techniques to detect specific IgE antibodies
      against single allergen molecules rather than whole extracts represents a
      significant advance in allergy diagnostics. The advantages of such component
      resolved diagnosis can be summarized as follows: (1) the ability to identify the
      truly responsible allergens in polysensitized patients, whether they be genuine
      (causing specific sensitization to their corresponding allergen source) or
      primary (the original sensitizing molecule); (2) distinguishing these allergens
      from simply cross-reactive components; (3) improving the appropriateness of the
      prescribed specific immunotherapy; and (4) identifying a risk profile for food
      allergens. Component-resolved diagnosis is performed using either a singleplex (1
      assay per sample) platform or a multiplex (multiple assays per sample) platform.
      Using an immuno solid-phase allergen chip microarray that falls into the latter
      category--it currently tests sensitivity to 112 allergens--may lead to a pitfall:
      detecting IgE to unexpected allergens, such as Hymenoptera venom. In fact,
      testing insect venom sensitivity in individuals with no history of reactions to
      stings is contrary to current guidelines and presents the physician with the
      dilemma of how to manage this information; moreover, this may become a legal
      issue. Based on what is currently known about venom allergy, it remains likely
      that a positive sensitization test result will have no clinical significance, but
      the possibility of reacting to a future sting cannot be completely ruled out.
      Because this problem has not been previously encountered using the more common
      allergy tests, no indications are currently available on how to effectively
      manage these cases.

PMID- 25609333
TI  - Safety of C1-esterase inhibitor in acute and prophylactic therapy of hereditary
      angioedema: findings from the ongoing international Berinert patient registry.
AB  - BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate,
      Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a
      substantial literature base that demonstrates safety and efficacy. Thromboembolic
      events have rarely been reported with C1-INH products, typically with off-label
      use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and
      clinical usage patterns of pasteurized C1-inhibitor concentrate and the more
      recent pasteurized, nanofiltered C1-INH, with a particular interest in
      thromboembolic events. METHODS: A registry was initiated in April 2010 at 27 US
      and 4 EU sites to obtain both prospective and retrospective safety and usage data
      on subjects who were administered C1-INH (Berinert). RESULTS: As of May 10, 2013,
      data were available for 135 subjects and 3196 infusions. By subject, 67.4% were
      using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and
      prophylactic administration. Approximately half of the infusions (49.5%) were
      administered for prophylaxis and >90% were given by the patient or a caregiver in
      the home setting. A total of 299 adverse events were reported, for an overall
      rate of 0.09 events per infusion with only 6 considered related to C1-INH. Two
      thromboembolic events were reported, both in patients with prothrombotic risk
      factors. CONCLUSION: This large pool of real-world clinical usage data in HAE
      further supports the extensive safety profile of 2 Berinert formulations when
      used on demand and/or for prophylaxis in both home and health care settings. No
      evidence was found to suggest that Berinert is an independent, causative risk
      factor for thromboembolic events.

PMID- 25609334
TI  - Adherence with allergen immunotherapy labeling guidelines.
AB  - BACKGROUND: Little is known about the adherence rate to allergen immunotherapy
      (AIT) labeling guidelines. OBJECTIVE: To assess adherence to labeling guidelines
      of AIT Practice Parameter 2011 at University of Michigan Health Service. METHODS:
      AIT vials of 320 patients who received their care at the University of Michigan
      Health Service were reviewed. Data collected looked at patient identifiers (PI),
      concentrations in volume/volume (v/v) format, color coding, allergen content,
      expiration date and instructions about AIT dosing, and systemic reaction
      treatment. Data were analyzed by using chi(2) test and the Fisher exact test and
      logistic regression. RESULTS: Of 238 non-university formulated labels, 65% had 2
      PIs, 62% had a v/v concentration, 41% had color coding, 71% had the content
      listed, and 100% had a recorded expiration date. Only 21% had all 5 recommended
      components. All 82 University vials had 5 components. Labels with 2 PIs were more
      likely to have a v/v concentration with its corresponding color coding (odds
      ratio [OR] 3.84 [95% CI, 1.9-7.7]; P < .001). Labels that specified the extract's
      content were more likely to be color coded or to have a v/v concentration listed
      (OR 6.3 [95% CI, 3.4-11.8]; P < .001). For all AIT vials, complete labels were
      significantly more likely to have a clear buildup schedule (OR 9.6 [95% CI, 4.2
      23.2]; P < .001), dosing adjustment after a missed dose (OR 8.2 [95% CI, 3.4
      19.8]; P < .001) or after a reaction (OR 13.7 [95% CI, 7.8-2.1]; P < .001), and
      clear systemic reaction treatment instructions (OR 9.7 [95% CI, 7.8-24.1]; P <
      .001). CONCLUSION: Fewer than 25% of the nonuniversity prescribers adhered to AIT
      practice parameters 5 years after publication. Recording 2 PIs, the v/v
      concentration, or the color coding increased the likelihood of having a complete
      label. Complete label contents were associated with clear instructions about AIT
      dosing and reaction treatment and/or dose adjustments.

PMID- 25609335
TI  - Characterization of anaphylaxis after ecallantide treatment of hereditary
      angioedema attacks.
AB  - BACKGROUND: Ecallantide is a human plasma kallikrein inhibitor indicated for
      treatment of acute attacks of hereditary angioedema for patients 12 years of age
      and older. Ecallantide is produced in Pichia pastoris yeast cells by recombinant
      DNA technology. Use of ecallantide has been associated with a risk of
      hypersensitivity reactions, including anaphylaxis. OBJECTIVE: The objective of
      this detailed retrospective data review was to characterize anaphylaxis cases
      within the ecallantide clinical trials database. METHODS: Potential cases of
      hypersensitivity reactions in the ecallantide clinical development program were
      identified by examining reported adverse events. The National Institute of
      Allergy and Infectious Disease criteria were used to identify those events that
      were consistent with anaphylaxis; these cases were then reviewed in detail.
      Results from investigational antibody testing also were examined. RESULTS: Among
      patients who received subcutaneous ecallantide (n = 230 patients; 1045 doses of
      30 mg ecallantide), 8 patients (3.5%) had reactions that met the National
      Institute of Allergy and Infectious Disease criteria for anaphylaxis; none
      occurred on first exposure to the drug. All 8 reactions had symptom onset within
      1 hour of exposure and cutaneous manifestations commonly observed in type I
      hypersensitivity reactions. All the reactions responded to standard management of
      type I hypersensitivity reactions and resolved without fatal outcomes. IgE
      antibody testing to ecallantide or P pastoris was not consistently positive in
      patients who experienced apparent type I hypersensitivity reactions. CONCLUSION:
      Anaphylaxis episodes after subcutaneous ecallantide exposure have clinical
      features suggestive of type I hypersensitivity reactions. However, anti
      ecallantide or anti-P pastoris IgE antibody status was not found to be reliably
      associated with anaphylaxis.

PMID- 25609336
TI  - Comparison of chromogenic and ELISA functional C1 inhibitor tests in diagnosing
      hereditary angioedema.
AB  - INTRODUCTION: Measuring functional C1 inhibitor (C1 INH) with chromogenic or
      ELISA methods can confirm a diagnosis of hereditary angioedema (HAE) due to C1
      INH deficiency. Previous studies found differences in the agreement of these
      assays. OBJECTIVE: To evaluate the agreement between chromogenic or ELISA methods
      in the context of an observational study. METHODS: Patients with previously
      confirmed HAE underwent functional C1 INH testing. These patients contacted first
      degree relatives (parents, siblings, or offspring) not previously evaluated for
      HAE, who underwent a panel of complement testing, including for functional C1
      INH. RESULTS: Overall, 31 patients with HAE and 46 untested relatives enrolled.
      Of 46 relatives, 14 (30.4%) were newly diagnosed with HAE based on their
      laboratory results. Among the 31 patients previously confirmed with HAE, all had
      low functional C1 INH according to the chromogenic method, whereas 22 (71.0%) had
      low, 7 (22.6%) had equivocal, and 2 (6.5%) had normal functional C1 INH according
      to the ELISA method. In the 14 newly diagnosed relatives, all had low functional
      C1 INH according to the chromogenic method, whereas 11 (78.5%) had low and 3
      (21.4%) had equivocal results according to the ELISA method. CONCLUSION: Despite
      the apparent discordance in the ELISA and chromogenic assays in a small number of
      patients, both were useful in measuring functional C1 INH. To establish the
      diagnosis of HAE due to C1 INH deficiency, functional C1 INH results should be
      interpreted in combination with family and clinical history, and with other
      complement tests.

PMID- 25609337
TI  - Anaphylaxis after cystoscopy.

PMID- 25609338
TI  - Conjunctival provocation tests: a predictive factor for patients' seasonal
      allergic rhinoconjunctivitis symptoms.
AB  - BACKGROUND: No parameters currently exist that can reliably predict the impact of
      preseasonal immunotherapy on the symptoms occurring during the season. OBJECTIVE:
      The purpose of our studies was to prove a correlation between preseasonal
      conjunctival allergen challenge and coseasonal primary clinical endpoints using
      the total combined score, ie, a combination of symptoms and medication score, as
      the primary outcome parameter. METHODS: Twelve weeks before both the birch and
      the grass pollen seasons, 2 separate prospective, double-blind, randomized,
      controlled studies were conducted followed by posttrial observations for each
      study during the active season. In the studies, patients who reacted to
      conjunctival allergen challenge were treated with sublingual immunotherapy
      tablets that contain either birch and/or alder or grass pollen allergoids.
      RESULTS: In all, 158 patients were included in the grass and 160 in the tree
      pollen study; of these, 100 and 109 patients, respectively, took part in the
      posttrial observations. When comparing patients with and without a positive
      reaction in the final conjunctival allergen challenge, the results revealed a
      significant difference in the total combined score (grass: P < .001; birch: P =
      .025). The same applied to the rescue medication score (P = .005; P = .025). A
      significant difference regarding the rhinoconjunctivitis symptom score was shown
      in the grass pollen study (P = .002), and the difference of well days was
      significant in the tree pollen study (P = .049). CONCLUSION: When comparing
      patients based on their reaction to allergen challenge after immunotherapy, each
      study leads to similarly significant results. Therefore, conjunctival allergen
      challenge can be used effectively as a parameter to predict allergic
      rhinoconjunctivitis symptoms during the season in patients treated with
      preseasonal sublingual immunotherapy tablets. Whether this can be transferred to
      untreated patients needs to be determined.

PMID- 25609339
TI  - Kaposi's Sarcoma in a Patient with Eosinophilic Granulomatosis with Polyangiitis
      While Taking Mycophenolate Mofetil.

PMID- 25609340
TI  - Understanding asthma medical nonadherence in an adult and pediatric population.

PMID- 25609341
TI  - Modified peanut oral immunotherapy protocol safely and effectively induces
      desensitization.

PMID- 25609342
TI  - The use of anti-IgE therapy beyond allergic asthma.
AB  - Omalizumab is a monoclonal anti-IgE antibody that has been used to treat allergic
      asthma for over a decade. The use of omalizumab to treat other diseases has
      largely been limited to case reports until the recently reported large
      multicenter studies that have established omalizumab as an effective treatment
      option for chronic spontaneous urticaria. The utility of omalizumab to treat
      nonallergic asthma and allergic rhinitis and the added safety and therapeutic
      benefits in combination with allergen immunotherapy have been demonstrated in
      placebo-controlled trials. Data supporting the clinical efficacy of omalizumab in
      treating atopic dermatitis, physical urticarias, mast cell disorders, food
      allergy, and various other allergic disorders have shown promise in small
      clinical trials and case studies. More carefully designed, large clinical trials
      of high quality are needed to fully appreciate the potential of omalizumab in
      treating various allergic and nonallergic diseases. 

PMID- 25609343
TI  - Amoxicillin allergy in children: five-day drug provocation test in the diagnosis
      of nonimmediate reactions.
AB  - BACKGROUND: The drug provocation test (DPT) is the gold standard to rule out drug
      hypersensitivity. There are standardized DPT protocols to diagnose immediate
      reactions to drugs, but not for nonimmediate reactions. OBJECTIVE: The aim of
      this study was to show the sensitivity and specificity of an allergy work-up that
      included a 5-day DPT in children with histories of nonimmediate reactions to
      amoxicillin through focusing on a pediatric population with histories of
      immediate and nonimmediate reactions to amoxicillin. METHODS: Two hundred
      consecutive patients with histories of amoxicillin reactions referred to the
      Allergy Unit of Anna Meyer Children's Hospital for suspected drug allergy from
      2008 to 2011 underwent in vivo tests with the culprit drug according to European
      Academy of Allergy and Clinical Immunology guidelines. Moreover, most of those
      children, regardless of the skin tests results, were challenged with amoxicillin
      for a total of 5 days. RESULTS: In 4 years, 200 patients were evaluated for a
      history of drug hypersensitivity to amoxicillin. The majority of patients (76%)
      had a history of mild nonimmediate reactions. All 200 patients underwent skin
      tests, and 9 of 200 tested positive. A total of 177 DPTs were performed with
      amoxicillin for 5 days in each child. Diagnosis of amoxicillin allergy was
      confirmed by a DPT in 17 patients (9.6%); 14/17 had history of nonimmediate
      reactions; 4/14 (26.6%) reacted on day 5. CONCLUSION: According to our results, a
      long-term DPT protocol increases the sensitivity of the allergy work-up, and it
      should be recommended for patients with a history of amoxicillin nonimmediate
      reaction.

PMID- 25609344
TI  - Successful rapid desensitization to imiglucerase in an adult patient with Gaucher
      disease and documented IgE-mediated hypersensitivity.

PMID- 25609345
TI  - Is it food allergy or frey syndrome?

PMID- 25609346
TI  - Clinical features of pediatric hereditary angioedema.
AB  - BACKGROUND: There is a paucity of data that describe the clinical course of
      hereditary angioedema (HAE) in children. OBJECTIVE: The purpose of this study was
      to examine the clinical features of children with HAE. METHODS: Electronic
      medical records from the past 10 years at Cincinnati Children's Hospital Medical
      Center and an outpatient allergy community practice were searched for ICD-9 code
      277.6 (Other deficiencies of circulating enzyme). Exclusion criteria included
      laboratory data not supportive of type I or II HAE diagnosis or age at diagnosis
      greater than 18 years. Chart review was performed and missing data were collected
      by telephone interviews with patient families. Descriptive statistics were
      performed using SAS version 9.4. RESULTS: Twenty-one children were identified.
      The median age was 13.2 years (interquartile range [IQR], 9.1-18.8), 71% were
      male, 86% had an HAE family history, and 95% were Caucasian. The median age of
      symptom onset and diagnosis was 5.7 (IQR, 5-9 years) and 5.0 (IQR, 4-8 years),
      respectively. Five children diagnosed were asymptomatic. Three children without a
      family history had a 6.0-year delay in diagnosis. The most common angioedema
      attack sites were abdominal, peripheral, and laryngeal, which occurred at least
      once in 93%, 73%, and 27%, respectively. Of the 15 children with onset of
      symptoms, only 6 children received on-demand therapy for an acute attack, whereas
      13 children were administered either short-term or long-term prophylaxis therapy.
      CONCLUSIONS: In this pediatric HAE population, symptom onset and diagnosis
      occurred at a median age of 5 years with a delay in diagnosis in those without a
      family history. Abdominal attacks were more common than peripheral attacks in
      this population.

PMID- 25609347
TI  - The association of blood eosinophil counts to future asthma exacerbations in
      children with persistent asthma.

PMID- 25609348
TI  - Epinephrine autoinjectors: does freezing or refrigeration affect epinephrine dose
      delivery and enantiomeric purity?

PMID- 25609349
TI  - Supraesophageal Reflux: Correlation of Position and Occurrence of Acid Reflux
      Effect of Head-of-Bed Elevation on Supine Reflux.
AB  - BACKGROUND: Supraesophageal reflux of gastric contents can contribute to
      perennial nasopharyngitis, cough, and asthma. However, effective treatment
      strategies for supraesophageal reflux disease (SERD) remain inadequately defined.
      OBJECTIVE: The purpose of this study is to assess the prevalence and timing of
      SERD and to investigate the efficacy of head-of-bed elevation in its treatment.
      METHODS: A retrospective chart review of patients seen at Scripps Clinic Division
      of Allergy, Asthma and Immunology was performed who had undergone overnight
      nasopharyngeal pH monitoring with a commercially available nasopharyngeal pH
      monitoring device, Dx-pH Measurement System from Restech, San Diego, Calif.
      Subjects with reflux were classified based on the position of reflux as either
      supine only, upright only, or both supine and upright. In a subset of subjects
      with supine-only reflux, pH monitoring was compared before and after elevating
      the head of bed 6 inches. RESULTS: Adequate nasopharyngeal pH-monitoring data
      were obtained for 235 patients. Reflux was detected in 113 (48%) patients. The
      pattern of reflux observed was 62 (55%) supine only, 4 (4%) upright only, and 47
      (42%) upright and supine. Sequential overnight nasopharyngeal pH monitoring
      before and after head-of-bed elevation was obtained in 13 individuals with supine
      only reflux. Ten subjects demonstrated significant improvement, 8 of whom
      demonstrated complete resolution of supine reflux with 6 inches of head-of-bed
      elevation. CONCLUSION: This study provides new evidence that SERD frequently
      occurs in the supine position and that 6 inches of head-of-bed elevation is
      effective in reducing supine SERD.

PMID- 25609350
TI  - Adjusting for nonresponse bias corrects overestimates of food allergy prevalence.

PMID- 25609351
TI  - A tailored mobile health intervention to improve adherence and asthma control in
      minority adolescents.

PMID- 25609352
TI  - Improving the Effectiveness of Penicillin Allergy De-labeling.
AB  - BACKGROUND: Approximately 10-20% of hospitalized patients are labeled as
      penicillin allergic, and this is associated with significant health and economic
      costs. OBJECTIVES: We looked at the effectiveness of penicillin allergy de
      labeling in clinical practice with the aim of deriving risk stratification models
      to guide testing strategies. METHODS: Consecutive patients aged 15 years or more,
      referred to a Western Australian public hospital drug allergy service between
      2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were
      conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and
      oral challenge (OC), and follow-up of post testing antibiotic usage were the main
      outcomes. RESULTS: SPT/IDT was performed in 401 consecutive patients with
      immediate (IMM) (<= 1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250)
      reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to >= 1 penicillin reagents,
      including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P <
      .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious
      positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive
      value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in
      almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151
      (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following
      the allergy label modifications (ALM) at the time of follow-up. CONCLUSIONS:
      Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and
      identifies selective beta-lactam allergies; however, incomplete adherence to ALM
      recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC
      reactions in patients with NIM reactions suggest OC alone to be a safe and cost
      effective de-labeling strategy that could improve the coverage of penicillin
      allergy de-labeling in lower risk populations.

PMID- 25609353
TI  - Epinephrine use in positive oral food challenges performed as a screening test
      for food allergy therapy trials.
AB  - BACKGROUND: Previous studies report epinephrine use for positive oral food
      challenges (OFCs) to be 9-11% when generally performed to determine outgrowth of
      food allergies. Epinephrine use for positive OFCs performed as screening criteria
      for enrollment in therapeutic trials for food allergy has not been reported.
      OBJECTIVE: The objective of this study was to assess the characteristics and
      treatment for positive OFCs performed for screening subjects for food therapeutic
      trials. METHODS: Retrospective review of positive screening OFCs from 2 treatment
      trials, food allergy herbal formula-2 (n = 45) and milk oral immunotherapy (n =
      29), conducted at the Icahn School of Medicine at Mount Sinai was performed.
      RESULTS: The most common initial symptom elicited was oral pruritus, reported for
      81% (n = 60) of subjects. Overall, subjective gastrointestinal symptoms (oral
      pruritus, throat pruritus, nausea, abdominal pain) were most common (97.3%
      subjects), followed by cutaneous symptoms (48.7%). Of the 74 positive double
      blind, placebo-controlled food challenge, 29 (39.2%) were treated with
      epinephrine; 2 of these subjects received 2 doses of epinephrine (6.9% of the
      reactions treated with epinephrine or 2.7% of all reactions). Biphasic reactions
      were infrequent, which occurred in 3 subjects (4%). CONCLUSIONS: Screening OFCs
      to confirm food allergies can be performed safely, but there was a higher rate of
      epinephrine use compared with OFCs used for assessing food allergy outgrowth.
      Therefore, personnel skilled and experienced in the recognition of early signs
      and symptoms of anaphylaxis who can promptly initiate treatment are required.

PMID- 25609354
TI  - Successful treatment of disseminated BCG in a patient with severe combined
      immunodeficiency.

PMID- 25609355
TI  - Uterotonic use immediately following birth: using a novel methodology to estimate
      population coverage in four countries.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal
      mortality in developing countries. While incidence of PPH can be dramatically
      reduced by uterotonic use immediately following birth (UUIFB) in both community
      and facility settings, national coverage estimates are rare. Most national health
      systems have no indicator to track this, and community-based measurements are
      even more scarce. To fill this information gap, a methodology for estimating
      national coverage for UUIFB was developed and piloted in four settings. METHODS:
      The rapid estimation methodology consisted of convening a group of national
      technical experts and using the Delphi method to come to consensus on key data
      elements that were applied to a simple algorithm, generating a non-precise
      national estimate of coverage of UUIFB. Data elements needed for the calculation
      were the distribution of births by location and estimates of UUIFB in each of
      those settings, adjusted to take account of stockout rates and potency of
      uterotonics. This exercise was conducted in 2013 in Mozambique, Tanzania, the
      state of Jharkhand in India, and Yemen. RESULTS: Available data showed that
      deliveries in public health facilities account for approximately half of births
      in Mozambique and Tanzania, 16% in Jharkhand and 24% of births in Yemen.
      Significant proportions of births occur in private facilities in Jharkhand and
      faith-based facilities in Tanzania. Estimated uterotonic use for facility births
      ranged from 70 to 100%. Uterotonics are not used routinely for PPH prevention at
      home births in any of the settings. National UUIFB coverage estimates of all
      births were 43% in Mozambique, 40% in Tanzania, 44% in Jharkhand, and 14% in
      Yemen. CONCLUSION: This methodology for estimating coverage of UUIFB was found to
      be feasible and acceptable. While the exercise produces imprecise estimates whose
      validity cannot be assessed objectively in the absence of a gold standard
      estimate, stakeholders felt they were accurate enough to be actionable. The
      exercise highlighted information and practice gaps and promoted discussion on
      ways to improve UUIFB measurement and coverage, particularly of home births.
      Further follow up is needed to verify actions taken. The methodology produces
      useful data to help accelerate efforts to reduce maternal mortality.

PMID- 25609356
TI  - In vitro evaluation of antiviral activity of tea seed saponins against porcine
      reproductive and respiratory syndrome virus.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of
      the major swine pathogens. This virus causes immune suppression and other
      secondary infections, leading to significant economic losses in the swine
      industry. Tea seed saponins (TS) are a natural extract from tea seeds with anti
      cancer, anti-inflammatory and antiviral activity. In this study, we demonstrated
      that TS possessed anti-PRRSV activity. METHODS: MTT assay and trypan blue
      staining were used to evaluate the cytotoxicity and antiviral ability of TS in
      cell culture. Apoptosis was measured to assess the safety of TS on Marc-145
      cells. Time-of-addition assay, entry inhibition assay and virucidal assay were
      used to assess the antiviral action of TS. The effect of TS on host cellular gene
      expression was analysed by real-time PCR. Absolute quantification RT-PCR and
      western blot were used to study the inhibitory effect of TS on PRRSV N gene and
      protein expression. RESULTS: Our results showed that 50% cytotoxic concentrations
      (CC50) and 50% effective concentration (EC50) of TS were 59.86 +/-0.3841 ug/ml
      and 24.29 +/-1.194 MUg/ml, respectively. The maximum non-cytotoxic concentration
      of TS on Marc-145 cells was 30 MUg/ml. TS inhibited PRRSV-induced cell apoptosis
      and effectively inhibited PRRSV replication by reducing the expression of host
      cellular gene PABP, and significantly inhibited virus N gene/protein expression.
      CONCLUSIONS: TS possessed anti-PRRSV activity in vitro and could serve as a
      potential antiviral drug for PRRSV prevention and control.

PMID- 25609357
TI  - Alterations of protein expression in conditions of copper-deprivation for
      Paracoccidioides lutzii in the presence of extracellular matrix components.
AB  - BACKGROUND: Paracoccidioides spp is a fungi genus and the agent of
      paracoccidioidomycosis. The strategies of infection used by these pathogens
      involve the expression of proteins related to adaptation to the host,
      particularly regarding the uptake of micronutrients. This study analyzed the
      adhesion of Paracoccidioides lutzii during conditions of copper (Cu) and iron
      (Fe) deprivation, while also evaluating the proteins expressed in conditions of
      Cu depletion in the presence of four extracellular matrix (ECM) components
      (laminin, fibronectin and types I and IV collagen). RESULTS: We cultured the P.
      lutzii in a chemically defined media without Cu and Fe. The fungus was then
      placed in contact with different ECM components and adhesion was evaluated. A
      significant increase in binding to all ECM components was observed when the
      fungus was cultured without Cu; which might be related to some adhesins
      expression. A proteomic assay was developed and revealed 39 proteins expressed
      that are involved in processes such as virulence, protein synthesis, metabolism,
      energy, transcription, transport, stress response and the cell cycle when the
      fungus was interacting with the ECM components. The up-regulated expression of
      two important adhesins, enolase and 14-3-3, was observed at the fungal cell wall
      during the interaction with the ECM components, indicating the role of these
      proteins in the Paracoccidioides-host interaction. CONCLUSIONS: This study is
      important for determining prospective proteins that may be involved in the
      interaction of Paracoccidioides with a host. Understanding the adaptive response
      to different growth conditions, elucidating the processes of adhesion and cell
      invasion, and identifying the proteins that are differentially expressed during
      the fungus-host interaction may help elucidate mechanisms used for survival and
      growth of Paracoccidioides in various human tissues.

PMID- 25609358
TI  - Imaging of pancreatic metastases from renal cell carcinoma.
AB  - BACKGROUND: To describe the main imaging characteristics of pancreatic metastases
      from renal cell carcinoma (RCC) with particular attention to CT features,
      underlining possible criteria for a differential diagnosis. METHODS: 15 patients
      have been included in this study. 14 patients underwent multislice CT with
      triphasic acquisition (unenhanced, pancreatic parenchymal and portal venous
      phases). In 9 cases a delayed phase (120 sec) was also acquired. 5 patients
      underwent MRI, before and after administration of gadolinium. RESULTS: The mean
      time interval between nephrectomy and recurrence was 7.5 years (range 1-17
      years). On CT metastases avidly enhanced in the parenchymal phase and then
      demonstrated a significant wash-out, approaching isodensity to the normal
      pancreatic parenchyma in the portal phase. In the portal phase 20 of the 25
      lesions found in the arterial phase were recognizable. On non-enhanced scans,
      only 13 of the 25 lesions were detected. CONCLUSION: Renal Cell Carcinomas
      require a prolonged CT or MRI follow-up.

PMID- 25609360
TI  - Drop the Likelihood Ratio. A Novel Non-electronic Tool for Interpreting
      Diagnostic Test Results.
AB  - OBJECTIVE: To present a geometric ruler to determine predictive values of binary
      diagnostic test results from prevalence, sensitivity and specificity without
      calculation. METHODS: On logarithmic scale the relationships between pre-/post
      test odds and the likelihood ratio as well as sensitivity, specificity and the
      likelihood ratio appear as simple linear (additive) equations. RESULTS: Each of
      these additive equations can be solved geometrically in form of a ruler with
      three scales. By amalgamation we devise a novel non-electronic tool which omits
      the intermediate step of likelihood ratio determination. CONCLUSIONS: We propose
      a simple geometric method to aid in interpretation of diagnostic test results for
      both practical and educational purposes.

PMID- 25609359
TI  - Morphological analysis of the acetabular cartilage surface in elderly subjects.
AB  - PURPOSE: The geometry of acetabular cartilage surface plays an important role in
      hip joint biomechanics. The aim of this study was to analyze the morphology of
      acetabular articular cartilage surface in elderly donated bodies to science using
      a 3D-digitizer. METHODS: Twenty hemipelves from 12 subjects (mean ages 85 years)
      were scanned with 3D-digitizer. Each acetabular surface model was divided into
      four regions: anterosuperior (AS), anteroinferior (AI), posterosuperior (PS), and
      posteroinferior (PI). In the global acetabulum and each region, the acetabular
      sphere radius and the standard deviation (SD) of the distance from the acetabular
      sphere center to the acetabular cartilage surface were calculated. In the global
      acetabulum, the distance between the acetabular surface model and the maximum
      sphere which did not penetrate over the acetabular surface model was calculated
      as the inferred femoral head, and then the distribution was mapped at intervals
      of 0.5 mm. RESULTS: The SD in AS was significantly larger than that in AI (p =
      0.006) and PI (p = 0.001). The SD in PS was significantly larger than that in PI
      (p = 0.005). The closest region (0-0.5 mm) tended to be distributed at anterior
      or posterosuperior acetabular edge. CONCLUSIONS: The contact between the femoral
      head and acetabulum might start at the periphery of the lunate surface,
      especially in the anterior or posterosuperior region. From viewpoint of
      acetabular morphology, the acetabular articular cartilage in the anterior or
      posterosuperior edge could be more vulnerable due to direct contact mechanism.

PMID- 25609361
TI  - Evaluating the translocation properties of a new nuclear targeted penetrating
      peptide using two fluorescent markers.
AB  - Human-derived cell penetrating peptides (CPPs) have attracted much more
      attentions than other CPPs which are limited by their potential toxicity and
      immunogenicity. Previously, we identified a novel human-originated CPP (named
      heparin-binding domain (HBD) in this article), which derived from the C-terminus
      of human extracellular superoxide dismutase, and demonstrated HBD is an efficient
      vector for delivering exogenous drug molecules such as apoptin into HeLa cells.
      In this study, we found this novel CPP showed differentiated efficiency in
      several tested cell lines. Heparin competitive inhibition experiment and
      heparanase pre-incubation experiment showed cell surface polysaccharides play an
      important role for the transmembrane transport. The results of endocytosis
      inhibitors suggested that HBD penetrates the cell membrane via a direct
      translocation, which is different from that of TAT, a classical clathrin-mediated
      endocytosis. HBD could deliver up to 90 kD protein cargoes into cells. Different
      conjugated modes with cargo molecules greatly affect their translocation
      efficiency. HBD also showed significant nuclear transport capacity when it was
      incubated with HeLa cells. Furthermore, the core region for HBD possessing
      membrane-penetrating ability was identified by deletion analyses. These results
      would be helpful for developing HBD as a new nuclear delivery tool for
      therapeutic biomolecules. 

PMID- 25609362
TI  - Effectiveness of localized ultrasound-targeted microbubble destruction with
      doxorubicin liposomes in H22 mouse hepatocellular carcinoma model.
AB  - OBJECTIVE: In order to increase local drug concentration and reduce systemic side
      effects of liver cancer chemotherapy, it is desirable to develop novel non
      invasive technologies for drug targeting, such as ultrasound-targeted microbubble
      destruction (UTMD). METHODS: H22 hepatocellular carcinoma (HCC) xenograft
      transplantation model was generated in UTMD study. BALB/c mice were randomly
      divided into six groups: doxorubicin HCl liposomal injection (DOX), DOX + US,
      UTMD, DOX + UTMD, H22 liver tumor control (CH control) and blank control group.
      The therapeutic schedule started on day 4 after tumor inoculation. RESULTS:
      Average survival time of the animal model was approximately 18 d. The UTMD
      therapy parameters were optimized in the H22 mouse model to be: microbubble (MB)
      diameter, 2.30 +/- 0.25 MUm; MB density, 4.0 * 10(9) bubbles/ml; treatment dose,
      0.2 ml per 20 g mouse body weight; sonication frequency, 1.3 MHz; and sonication
      power, 2.06 W/cm(2). Mice treated with DOX + UTMD had the smallest tumor volume
      and weight (p < 0.001), and the highest tumor inhibition rate (p < 0.01),
      intratumoral DOX concentration (p < 0.001) and survival rate among all tumor
      burden groups (p < 0.001). Cell viability in different treatment groups was also
      assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. CONCLUSION: An improved antitumor effect was observed with the combination
      therapy of DOX and UTMD, as compared with treatment with DOX, DOX + US or UTMD,
      which implicates a novel approach for HCC treatment.

PMID- 25609363
TI  - Proteogenomics: emergence and promise.
AB  - Proteogenomics, or the integration of proteomics with genomics and
      transcriptomics, is emerging as the next step towards a unified understanding of
      cellular functions. Looking globally and simultaneously at gene structure, RNA
      expression, protein synthesis and post-translational modifications have become
      technically feasible and offer a new perspective to molecular processes. Recent
      publications have highlighted the value of proteogenomics in oncology for
      defining the molecular signature of human tumors, and translation to other areas
      of biomedicine and life sciences is anticipated. This mini-review will discuss
      recent developments, challenges and perspectives in proteogenomics. 

PMID- 25609365
TI  - Whole-Plant Growth and N Utilization in Transgenic Rice Plants with Increased or
      Decreased Rubisco Content under Different CO2 Partial Pressures.

PMID- 25609366
TI  - High sodium causes hypertension: evidence from clinical trials and animal
      experiments.
AB  - Hypertension is a cardiovascular disease affecting approximately one out of every
      seven people worldwide. High-sodium consumption has been generally accepted as a
      risk factor for developing hypertension. Today, global sodium consumption greatly
      exceeds guidelines recommended by all medical institutions. This review
      synthesizes the data of landmark mammalian and human studies which investigated
      the role of sodium in the pathogenesis of hypertension, along with modern studies
      questioning this relationship. Recent studies concerning the potential pathways
      by which high-sodium concentration induces hypertension were reviewed. Human
      trials and population studies revealed a strong correlation between high blood
      pressure and average dietary sodium; and animal studies found a dramatic
      reduction in vascular function in a variety of mammals treated with high-sodium
      diets. In spite of a few contrarian studies, we found overwhelming evidence that
      elevated sodium consumption could cause hypertension. 

PMID- 25609364
TI  - Dysregulated glycolysis as an oncogenic event.
AB  - Enhanced glycolysis in cancer, called the Warburg effect, is a well-known feature
      of cancer metabolism. Recent advances revealed that the Warburg effect is coupled
      to many other cancer properties, including adaptation to hypoxia and low
      nutrients, immortalisation, resistance to oxidative stress and apoptotic stimuli,
      and elevated biomass synthesis. These linkages are mediated by various oncogenic
      molecules and signals, such as c-Myc, p53, and the insulin/Ras pathway.
      Furthermore, several regulators of glycolysis have been recently identified as
      oncogene candidates, including the hypoxia-inducible factor pathway, sirtuins,
      adenosine monophosphate-activated kinase, glycolytic pyruvate kinase M2,
      phosphoglycerate mutase, and oncometabolites. The interplay between glycolysis
      and oncogenic events will be the focus of this review.

PMID- 25609367
TI  - SimTCM: A human patient simulator with application to diagnostic accuracy studies
      of Chinese medicine.
AB  - OBJECTIVE: The aim of this work is to develop and implement the SimTCM, an
      advanced computational model that incorporates relevant aspects from traditional
      Chinese medicine (TCM) theory as well as advanced statistical and epidemiological
      techniques for simulation and analysis of human patients. METHODS: SimTCM
      presents five major attributes for simulation: representation of true and false
      profiles for any single pattern; variable count of manifestations for each
      manifestation profile; empirical distributions of patterns and manifestations in
      a disease-specific population; incorporation of uncertainty in clinical data; and
      the combination of the four examinations. The proposed model is strengthened by
      following international standards for reporting diagnostic accuracy studies, and
      incorporates these standards in its treatment of study population, sample size
      calculation, data collection of manifestation profiles, exclusion criteria and
      missing data handling, reference standards, randomization and blinding, and test
      reproducibility. RESULTS: Simulations using data from patients diagnosed with
      hypertension and post-stroke sensory-motor impairments yielded no significant
      differences between expected and simulated frequencies of patterns (P=0.22 or
      higher). Time for convergence of simulations varied from 9.90 s (9.80, 10.27) to
      28.31 s (26.33, 29.52). The ratio iteration profile necessary for convergence
      varied between 1:1 and 5:1. CONCLUSION: This model is directly connected to
      forthcoming models in a large project to design and implement the SuiteTCM:
      ProntTCM, SciTCM, DiagTCM, StudentTCM, ResearchTCM, HerbsTCM, AcuTCM, and
      DataTCM. It is expected that the continuity of the SuiteTCM project enhances the
      evidence-based practice of Chinese medicine. The software is freely available for
      download at: http://suitetcm.unisuam.edu.br.

PMID- 25609368
TI  - The effects of Park sham needles: a pilot study.
AB  - BACKGROUND: When performing clinical trials involving acupuncture, it can be
      difficult to choose a placebo control. OBJECTIVE: To validate the Park sham
      needle for use as a double-blind control intervention. DESIGN, SETTING,
      PARTICIPANTS AND INTERVENTIONS: Two different methods were employed. First, a
      researcher blinded to needle type administered the Park sham or a real needle,
      chosen at random, on the arms of 16 healthy volunteers. The researcher and the
      volunteers independently recorded which needle type they thought had been applied
      at each acupuncture point. Second, 19 patients with shoulder impingement syndrome
      were randomly assigned to receive acupuncture applied with the real needle or the
      Park sham needle, once a week for 6 weeks alongside a course of physiotherapy. At
      the end of the 6 sessions the patients recorded which needle type they thought
      was being used. The results were analyzed with a Fisher's exact test. This study
      was carried out in the Outpatient Department of Physiotherapy in Charing Cross
      Hospital, London, UK, on healthy volunteers and patients with shoulder
      impingement pain. The age range was 23 to 54 and 22 to 74 years respectively.
      RESULTS: Of the healthy volunteers, there was no difference (P=0.23) between the
      number of needles that were correctly (n=43) or incorrectly identified (n=53).
      All patients thought that they had received the real needles. The researcher
      correctly identified all needles that were applied. CONCLUSION: The researcher
      delivering the acupuncture recognized the needle type. However, both healthy and
      patient volunteers were blind to the needle type. This demonstrates that the Park
      sham needle is an effective single-blind control. It should be noted that the
      number of patients recruited was small and the study was underpowered to detect
      an effect of treatment.

PMID- 25609369
TI  - Saponins isolated from roots of Chlorophytum borivilianum reduce acute and
      chronic inflammation and histone deacetylase.
AB  - OBJECTIVE: The roots of Chlorophytum borivilanum are used in traditional medicine
      for the treatment of arthritis and inflammation. The aim of the work was to
      evaluate the anti-inflammatory activity of isolated saponins from Chlorophytum
      borivilianum (ISCB). METHODS: The ISCB was screened using the carrageenan-induced
      paw edema, histamine-induced paw edema, cotton pellet-induced granuloma, and
      Freund's adjuvant-induced arthritis in rats at orally administered doses of 3,
      10, and 30 mg/kg. Effect of ISCB on histone deacetylase (HDAC) level was measured
      by the HDAC assay at the highest dose (30 mg/kg). RESULTS: The results showed
      that the ISCB significantly reduced carrageenan-induced inflammation, histamine
      induced inflammation, cotton pellet-induced granuloma and Freund's adjuvant
      induced arthritis in rats. The ISCB at a dose of 30 mg/kg significantly inhibited
      HDAC level in rat paw tissue. CONCLUSION: It is concluded that saponins isolated
      from roots of C. borivilianum possess anti-inflammatory and anti-arthritic
      properties. ISCB may act by inhibiting histamine, prostaglandin and HDAC. This
      suggests that ISCBs have potential for therapeutic use in the treatment of
      inflammation and arthritis.

PMID- 25609370
TI  - Evaluation of chemopreventive potentials of ethanolic extract of Ruta graveolens
      against A375 skin melanoma cells in vitro and induced skin cancer in mice in
      vivo.
AB  - OBJECTIVE: Chemopreventive approach with natural products, particularly plants
      and plant-derived ones, is receiving increasing attention for their effective
      role against cancer without any palpable side effects. In this study, efficacy of
      ethanolic extract of Ruta graveolens (RG) on skin melanoma cells (A375) in vitro
      and on 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer in vivo has been
      tested in Swiss albino mice. METHODS: Studies on cell viability, apoptosis and
      autophagy induction were conducted in vitro. To check apoptosis, assays like
      alteration in mitochondrial membrane potential, annexin V-fluorescein
      isothiocyanate/propidium iodide assay and immunoblot were performed. Fluorescence
      microscopic and immunoblot assays were performed to confirm autophagy induction.
      The effects of RG were determined by evaluating body weight, tumor incidence,
      tumor volume and tumor burden in mice. Enzymatic and non-enzymatic antioxidant
      status was assessed. The role of some relevant signaling proteins was also
      analyzed. RESULTS: RG caused death of A375 cells through induction of caspase 3
      mediated apoptosis and Beclin-1-associated autophagy. Moreover, RG administration
      (75 mg/kg body weight) which showed no acute or chronic toxicity, showed
      significant reduction in the skin tumor burden of DMBA-painted mice. RG also
      demonstrated potent anti-lipid peroxidative and antioxidant functions during the
      course of skin cancer induction by DMBA. CONCLUSION: Chemopreventive potential of
      RG was demonstrated from overall results of this study, indicating its possible
      use in therapeutic formulation of an effective drug to treat skin cancer.

PMID- 25609371
TI  - Antibacterial efficacy of five medicinal plants against multidrug-resistant
      enteropathogenic bacteria infecting under-5 hospitalized children.
AB  - OBJECTIVE: To evaluate in vitro antibacterial effectiveness of five medicinal
      plants used by an Indian aborigine, against 8 multidrug-resistant (MDR)
      enteropathogenic bacteria isolated from clinical samples of under-5 hospitalized
      children. METHODS: Antibiotic sensitivity patterns of eight clinically isolated
      strains of enteropathogenic bacteria, Enterobacter aerogenes, Escherichia coli,
      Klebsiella pneumoniae, Salmonella paratyphi, S. typhi, Shigella dysenteriae, S.
      sonnei and Vibrio cholerae were assessed by disc-diffusion method. Antibacterial
      activities of 8 solvent-extracts of leaves and bark of five medicinal plants were
      monitored by the agar-well diffusion method. The microbroth dilution method was
      used to assess minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC). Qualitative phytochemical analyses of active plant extracts
      were carried out. RESULTS: Ethanol, ethyl acetate and methanol extracts of
      Holarrhena antidysenterica leaf tissue were most effective against 8 MDR
      pathogens in vitro. Similarly, acetone, ethanol and methanol extracts of
      Terminalia alata leaf tissue; chloroform, ethyl acetate and methanol extracts of
      Terminalia arjuna leaf tissue and ethyl acetate, ethanol and methanol extracts of
      Paederia foetida leaf tissue were most effective in inhibiting in vitro growth of
      the 8 MDR enteropathogens. Ethyl acetate and methanol extracts of H.
      antidysenterica bark tissue; acetone, ethanol and methanol extracts of T. alata
      bark tissue and acetone, ethanol and methanol extracts of T. arjuna bark tissue
      were most effective in controlling enteropathogen growth. The minimum inhibitory
      concentration and minimum bactericidal concentration values of the 3 most
      antimicrobial leaf and bark extracts from the five plants were in the range of
      1.56 to 50 mg/mL. CONCLUSION: These 5 plants exhibited in vitro control over a
      cohort of 8 enteropathogenic bacterial strains isolated from clinical samples.

PMID- 25609372
TI  - Symptomatic Tarlov cyst and electroacupuncture: more studies required.

PMID- 25609373
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      diseases of paediatrics (part 1).

PMID- 25609374
TI  - Native serotonin 5-HT2C receptors are expressed as homodimers on the apical
      surface of choroid plexus epithelial cells.
AB  - G protein-coupled receptors (GPCRs) are a prominent class of plasma membrane
      proteins that regulate physiologic responses to a wide variety of stimuli and
      therapeutic agents. Although GPCR oligomerization has been studied extensively in
      recombinant cells, it remains uncertain whether native receptors expressed in
      their natural cellular environment are monomers, dimers, or oligomers. The goal
      of this study was to determine the monomer/oligomer status of a native GPCR
      endogenously expressed in its natural cellular environment. Native 5-HT2C
      receptors in choroid plexus epithelial cells were evaluated using fluorescence
      correlation spectroscopy (FCS) with photon counting histogram (PCH). An anti-5
      HT2C fragment antigen binding protein was used to label native 5-HT2C receptors.
      A known monomeric receptor (CD-86) served as a control for decoding the oligomer
      status of native 5-HT2C receptors by molecular brightness analysis. FCS with PCH
      revealed molecular brightness values for native 5-HT2C receptors equivalent to
      the molecular brightness of a homodimer. 5-HT2C receptors displayed a diffusion
      coefficient of 5 * 10(-9) cm(2)/s and were expressed at 32 receptors/MUm(2) on
      the apical surface of choroid plexus epithelial cells. The functional
      significance and signaling capabilities of the homodimer were investigated in
      human embryonic kidney 293 cells using agonists that bind in a wash-resistant
      manner to one or both protomers of the homodimer. Whereas agonist binding to one
      protomer resulted in G protein activation, maximal stimulation required occupancy
      of both protomers. This study is the first to demonstrate the homodimeric
      structure of 5-HT2C receptors endogenously expressed in their native cellular
      environment, and identifies the homodimer as a functional signaling unit. 

PMID- 25609375
TI  - Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to
      Generation 5 Polypropyleneimine.
AB  - Gene therapy is a novel method to treat a variety of diseases including genetic
      disorders and cancer. Nonviral gene carriers have now gained considerable
      attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine
      (PPI) are the two most widely used denderimers in gene delivery studies. The aim
      of the current study was to investigate the effects of modification of generation
      5 polypropyleneimine (G5 PPI) dendrimers with alkanoate groups as hydrophobic
      moieties on DNA transfection and cytotoxicity. Six, 10, and 16 carbon derivatives
      of bromoalkanoic acids were conjugated onto PPI with 10%, 30%, and 50% of surface
      amine grafting. Ethidium bromide exclusion assay results proved the ability of
      modified carriers to condense DNA. Transfection assay showed higher DNA delivery
      potential for 30% and 50% grafting with decanoate moieties compared to native G5
      PPI and Superfect(TM). 3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyltetrazolium
      bromide (MTT) and apoptosis experiments showed lower toxicity for modified
      carriers compared to unmodified PPI. The hemolytic effect of grafted carriers was
      not significantly different from G5 PPI. Size and zeta potential measurements
      revealed that polyplex size was less than 200 nm and electrical charges were in
      the range 14-25 mV. The hydrophobic modifications improved transfection activity
      and toxicity of G5 PPI without negatively affecting hemocompatibility. These
      modified carriers are therefore promising candidates for further in vivo
      investigations.

PMID- 25609376
TI  - Development and Evaluation of Diclofenac Sodium Loaded-N-Trimethyl Chitosan
      Nanoparticles for Ophthalmic Use.
AB  - The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular
      inflammation is presently available in the market only as an eye drop solution.
      Due to its low occular bioavailability, it requires frequent application leading
      to low patients' compliance and quality of life. This study was conducted to
      develop formulations of DC loaded-N-trimethyl chitosan nanoparticles (DC-TMCNs)
      for ophthalmic use to improve ocular biavailabiltiy of DC. DC-TMCNs varied in
      formulation compositions were prepared using ionic gelation technique and
      evaluated for their physicochemical properties, drug release, eye irritation
      potential, and ophthalmic absorption of diclofenac sodium. N-Trimethyl chitosan
      (TMC) with a 49.8% degree of quaternization was synthesized and used for DC-TMCNs
      production. The obtained DC-TMCNs had particle size in a range of 130-190 nm with
      zeta potential values of +4 to +9 mV and drug entrapment efficiencies of more
      than 70% depending on the content of TMC and sodium tripolyphosphate (TPP). The
      optimized DC-TMCNs formulation contained TMC, DC, and TPP at a weight ratio of
      TMC/DC/TPP = 3:1:1. Their lyophilized product reconstituted with phosphate buffer
      solution pH 5.5 possessed a drug release pattern that fitted within the zero
      order model. The eye irritation tests showed that DC-TMCNs were safe for
      ophthalmic use. The in vivo ophthalmic drug absorption study performed on rabbits
      indicated that DC-TMCNs could improve ophthalmic bioavailability of DC. Results
      of this study suggested that DC-TMCNs had potential for use as an alternative to
      conventional DC eye drops for ophthalmic inflammation treatment.

PMID- 25609377
TI  - Investigating transdermal delivery of vitamin D3.
AB  - Transdermal delivery of therapeutic amounts of vitamin D3 is proposed to overcome
      its variable oral bioavailability, especially for people who suffer from fat
      malabsorption. The main challenge for this delivery route is to overcome the
      barrier properties of skin, especially for very lipophilic compounds such as
      vitamin D3. In this study, the effect of different penetration enhancers, such as
      oleic acid, dodecylamine, ethanol, oleic acid in propylene glycol, isopropyl
      myristate, octyldodecanol, and oleyl alcohol in propylene glycol were evaluated
      in vitro for their effectiveness in delivering vitamin D3 through polyamide
      filter, polydimethylsiloxane membrane, and porcine skin. A diffusion cell was
      used to study the transdermal permeability of vitamin D3. Ointment formulations
      of vitamin D3 were prepared containing the most widely used penetration
      enhancers, oleic acid, and dodecylamine. The ointment containing oleic acid as
      chemical penetration enhancer did not improve delivery compared to control. On
      the other hand, the formulation containing dodecylamine as a penetration enhancer
      did improve the transdermal delivery of vitamin D3. However, statistical
      significance and an amount high enough for nutritional supplementation purposes
      were reached only when the skin was pretreated with 50% ethanol. In these
      conditions, the ointment delivered an amount of 760-ng vitamin D3 per cm(2) of
      skin. The research shows promise that transdermal delivery could be an effective
      administration route for vitamin D3 when ethanol and dodecylamine are used as
      penetration enhancers. 

PMID- 25609378
TI  - The anti-melanoma efficiency of the intratumoral injection of cucurbitacin-loaded
      sustained release carriers: in situ-forming implants.
AB  - Our previous studies revealed that the PLGA-based particulate systems loaded with
      cucurbitacin showed limited anti-melanoma efficiency in xenograft animal models
      after intratumoral injection, which was due to the undesirable initial burst
      release and the leakage of the particulate carriers from the injection site
      through the pinhole. In this paper, two categories of in situ-forming implants
      (ISFIs) for intratumoral injection, PLGA ISFIs and SAIB ISFIs, were systemically
      evaluated for their potentials for on solid tumor treatment via intratumoral
      injection. The in vitro drug release profiles of these two ISFIs were different
      due to the different sol-gel transition properties. The pharmacodynamics results
      revealed that SAIB ISFIs displayed obvious therapeutic efficiencies to melanoma,
      and multi-points injection of SASIB ISFIs displayed better efficiency than single
      point injection. The different sol-gel transition properties and mechanism for
      PLGA ISFIs and SAIB ISFIs affected both the drug release and strongly impacted
      the pharmacokinetic parameters and pharmacodynamic effectiveness. Also, the
      adhesive property of SAIB to the local tissue could extend the retention and
      inhibit the leakage of the SAIB ISFIs, thus enhanced the anticancer
      effectiveness. Comparison of the various intratumoral injection systems,
      appropriate drug release profiles (lower initial burst and steady release) and
      good retention (minimum leakage from the injection site) would benefit to the
      antitumor effects of the intratumoral depots. 

PMID- 25609379
TI  - Intraoperative vascular DIVA surgery reveals angiogenic hotspots in tumor zones
      of malignant gliomas.
AB  - Malignant gliomas belong to the most threatening tumor entities and are
      hallmarked by rapid proliferation, hypervascularization and an invasive growth
      pattern. The primary obstacle in surgical treatment lies in differentiation
      between healthy and pathological tissue at the tumor margins, where current
      visualization methods reach their limits. Here, we report on a novel technique
      (vascular dual intraoperative visualization approach - vDIVA) enabling
      visualization of different tumor zones (TZ I-III) on the basis of angiogenic
      hotspots. We investigated glioblastoma patients who underwent 5-ALA fluorescence
      guided surgery with simultaneous intraoperative ICG fluorescence angiography.
      This vDIVA technique revealed hypervascularized areas which were further
      histologically investigated. Neuropathological assessments revealed tissue areas
      at the resection margins corresponding to TZ II, and postoperative CD34- and Map2
      immunostaining confirmed these angiogenic hotspots to be occupied by glioma
      cells. Hence, the vascular architecture in this transitional zone could be well
      differentiated from both primary tumor bulk and healthy brain parenchyma. These
      data demonstrate that ICG fluorescence angiography improves state-of-the-art
      glioma surgery techniques and facilitates the future characterization of
      polyclonal attributes of malignant gliomas. 

PMID- 25609381
TI  - PD-L1hi B cells are critical regulators of humoral immunity.
AB  - Specific B-cell subsets can regulate T-cell immune responses, and are termed
      regulatory B cells (Breg). The majority of Breg cells described in mouse and man
      have been identified by IL-10 production and are known to suppress allergy and
      autoimmunity. However, Breg cell mediated immune suppression, independent of IL
      10, also occurs. Here we show that Breg cells play a critical role in regulating
      humoral immunity mediated by CD4(+)CXCR5(+)PD-1(+) follicular helper T cells, and
      can suppress inflammation in autoimmune disease through elevated expression of PD
      L1. We have also identified that these B cells are resistant to alphaCD20 B-cell
      depletion. This work describes how Breg cells are critical in humoral
      homoeostasis and may have implications for the regulation of autoimmune diseases.

PMID- 25609380
TI  - Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear
      sturdiness.
AB  - In most metazoan nuclei, heterochromatin is located at the nuclear periphery in
      contact with the nuclear lamina, which provides mechanical stability to the
      nucleus. We show that in cultured cells, chromatin decompaction by the nucleosome
      binding protein HMGN5 decreases the sturdiness, elasticity and rigidity of the
      nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are
      normal at birth but develop hypertrophic heart with large cardiomyoctyes,
      deformed nuclei and disrupted lamina and die of cardiac malfunction. Chromatin
      decompaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with
      disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of
      heterochromatin diminishes the ability of the nucleus to withstand the mechanical
      forces of the contracting heart. Thus, heterochromatin enhances the ability of
      the nuclear lamina to maintain the sturdiness and shape of the eukaryotic
      nucleus; a structural role for chromatin that is distinct from its genetic
      functions. 

PMID- 25609382
TI  - Correlation between semiquantitative sonoelastography and immunohistochemistry in
      the evaluation of testicular focal lesions.
AB  - BACKGROUND: Sonoelastography is a novel and promising imaging tool, which has
      been applied to breast, thyroid, and prostate tissues. The aim of this study was
      to evaluate focal lesions of the testes with diameters of <10 mm using
      sonoelastography, B-mode sonography (US), and colour Doppler ultrasonography
      (CDU). METHODS: Thirty patients who were referred to our outpatient clinics for
      varicocoeles, scrotal pain, scrotal enlargements, epididymitis, palpable
      testicular nodules, or infertility, were prospectively enrolled into this study.
      Ultrasound evaluations had revealed that 27 subjects had focal testicular lesions
      with diameters of <10 mm and 3 subjects had 10-mm spherical non-homogeneous
      testicular nodules. All lesions were evaluated using semiquantitative
      sonoelastography, and the patients underwent orchifunicolectomies. The testicular
      lesions were examined histopathologically. The vascularization of the lesions and
      the surrounding testicular parenchyma was evaluated by analysing the
      immunohistochemical distribution of the cluster of differentiation 31 and by
      calculating the vascular indices (VI). Potential associations between the strain
      ratios (stiffness of the lesions) and the VI were tested. RESULTS: Analyses of
      the strain fields obtained using semiquantitative sonoelastography yielded
      different values for the masses and the surrounding tissues, which led to
      significant increases in the strain ratios. Sonoelastography upheld all of the
      diagnoses that were suspected when the patients were physically examined, when
      the serum markers were analysed, and after the patients had undergone US and CDU.
      Histopathological examinations confirmed the neoplastic characteristics of these
      masses. A significant inverse correlation was determined between the
      sonoelastographic strain ratio and the VI (Pearson correlation coefficient, r, = 
      0.93; P < 0.001). CONCLUSION: Our investigation shows that semiquantitative
      sonoelastography may provide additional objective information to support the
      algorithm used to diagnose testicular lesions. This might be of crucial
      diagnostic importance for lesions with diameters of <10 mm, particularly if they
      are not palpable, are negative for serum tumour markers, and if the findings from
      ultrasonography and CDU are equivocal. The findings from semiquantitative
      sonoelastography might indicate the need for surgical exploration. Further
      investigations with larger numbers of patients are required to corroborate these
      data and to support the use of semiquantitative sonoelastography in the
      evaluation of testicular lesions.

PMID- 25609383
TI  - Iron deficiency in gastrointestinal oncology.

PMID- 25609384
TI  - Role of thrombophilia testing: con.

PMID- 25609385
TI  - Technological assumptions for biogas purification.
AB  - Biogas can be used in the engines of transport vehicles and blended into natural
      gas networks, but it also requires the removal of carbon dioxide, hydrogen
      sulphide, and moisture. Biogas purification process flow diagrams have been
      developed for a process enabling the use of a dolomite suspension, as well as for
      solutions obtained by the filtration of the suspension, to obtain biogas free of
      hydrogen sulphide and with a carbon dioxide content that does not exceed 2%. The
      cost of biogas purification was evaluated on the basis of data on biogas
      production capacity and biogas production cost obtained from local water
      treatment facilities. It has been found that, with the use of dolomite
      suspension, the cost of biogas purification is approximately six times lower than
      that in the case of using a chemical sorbent such as monoethanolamine. The
      results showed travelling costs using biogas purified by dolomite suspension are
      nearly 1.5 time lower than travelling costs using gasoline and slightly lower
      than travelling costs using mineral diesel fuel. 

PMID- 25609386
TI  - Diagnostic miss rate for colorectal cancer: an audit.
AB  - BACKGROUND: Colorectal cancer (CRC) is a common cancer worldwide. While screening
      improves survival, avoiding delayed diagnosis in symptomatic patients is crucial.
      Computed tomographic colonography (CTC) or colonoscopy is recommended as first
      line investigation and most societies recommend counseling patients undergoing
      colonoscopy about a miss rate of 5%. This audit evaluates "miss rate" of
      colorectal investigations, which have led to diagnostic delay in symptomatic
      cases in a district general hospital in the United Kingdom. METHODS: This is a
      retrospective review of 150 consecutive CRC cases presenting between August 2010
      and July 2011. Evidence of bowel investigations done in the 3 years prior to
      diagnosis was obtained from computerized health records. Data regarding previous
      bowel investigations such as colonoscopy, CTC, double contrast barium enema
      (DCBE), and CT abdomen/pelvis were collected. RESULTS: 6.7% cases were identified
      via screening pathway while 93% were identified through symptomatic pathway. 17%
      (26/150) of newly diagnosed CRC had been investigated in the preceding 3 years.
      Of these, 8% (12/150) had false negative results. The false negative rate for CRC
      diagnosis was 3.5% for colonoscopy (3/85), 6.7% for CTC (1/17), 9.4% for CT
      (5/53), and 26.7% for DCBE (4/15). Some patients had a missed diagnosis despite
      more than one diagnostic test. Time delay to diagnosis ranged from 21-456 days.
      CONCLUSIONS: 17% of patients diagnosed with CRC had been investigated in the
      previous 3 years. Higher miss rate of barium enema should preclude its use as a
      first-line modality to investigate CRC.

PMID- 25609389
TI  - [Editorial].

PMID- 25609387
TI  - Evidence for an oxygen evolving iron-oxo-cerium intermediate in iron-catalysed
      water oxidation.
AB  - The non-haem iron complex alpha-[Fe(II)(CF3SO3)2(mcp)] (mcp=(N,N'-dimethyl-N,N'
      bis(2-pyridylmethyl)-1,2-cis-diaminocyclohexane) reacts with Ce(IV) to oxidize
      water to O2, representing an iron-based functional model for the oxygen evolving
      complex of photosystem II. Here we trap an intermediate, characterized by
      cryospray ionization high resolution mass spectrometry and resonance Raman
      spectroscopy, and formulated as [(mcp)Fe(IV)(O)(MU-O)Ce(IV)(NO3)3](+), the first
      example of a well-characterized inner-sphere complex to be formed in cerium(IV)
      mediated water oxidation. The identification of this reactive Fe(IV)-O-Ce(IV)
      adduct may open new pathways to validate mechanistic notions of an analogous
      Mn(V)-O-Ca(II) unit in the oxygen evolving complex that is responsible for
      carrying out the key O-O bond forming step. 

PMID- 25609390
TI  - [Psychotherapeutically Competent Child Guidance-General Framework and Legal
      Foundations].
AB  - Assistances in education are pedagogical and therapeutic benefits connected with
      it. For child guidance as an assistance in education therefore psychotherapeutic
      competence is constitutive. The article describes the professional and legal
      framework of a psychotherapy in child guidance. It specifies on the one hand the
      composition of the multi disciplinary team (including child and youth
      psychotherapists and psychological psychotherapists) and the additional
      therapeutic qualifications acquired by the skilled employees. On the other hand
      it traces the judicial border between a medical psychotherapy with its
      scientifically recognised psychotherapy procedures and methods and a
      psychotherapy in child guidance. The applicability of the new law on the rights
      of patients with its requirements on a contract governing medical treatment
      (standards of medical specialists, duty to provide information, information
      provided for self-determination as well as documentation) on child guidance is
      discussed as well. The author argues for the preservation of psychotherapeutic
      competence in child guidance as a benefit sui generis and sees precisely in its
      therapeutic competence its specific contribution to the advancement of the
      assistances in education. 

PMID- 25609391
TI  - [Anxious School Absenteeism: Cognitive-Behavioral Treatment of School Phobia at a
      Psychological Counseling Center].
AB  - Resulting from a shortage of possibilities in the ambulant treatment of school
      phobia behavior-therapeutic interventions were established at a psychological
      counseling center for families twenty years ago, which have been in existence to
      this day. The criteria of anxiety-based absenteeism as well as problems of
      terminology and classification will be presented with emphasis on school phobia
      as a combination of separation anxiety and social anxiety ("Schulphobie"). The
      multimodal treatment focuses on cognitive interventions, graduated exposition and
      close cooperation with teachers. The counselor is also in charge of the
      networking and cooperation of all people concerned. A short case study is used to
      illustrate the process. Measures such as training and information for teachers
      and school social workers and a manual for the comprehension and the treatment of
      school phobia, which was edited in cooperation with a psychological counseling
      center for schools complement the treatment. 

PMID- 25609392
TI  - [Psychodynamic Psychotherapy and Educational Counseling].
AB  - The attempts to differentiate, separate and draw lines between counseling,
      educational counseling and psychotherapy are fundamentally flawed. There are no
      clear distinctions between these areas with a view to the techniques, procedures
      and methods used. In the context of counseling psychotherapeutic interventions
      are also necessary to overcome the problems. This will be shown in three case
      studies on the grounds of the following principles of psychodynamic
      psychotherapy: unconscious conflicts - defence/resistance -
      transference/countertransference - clarification/confrontation/interpretation. 

PMID- 25609393
TI  - [Children's Aggressive Behaviour and Therapeutic Interventions on the Parental
      Couple Level].
AB  - Parents go to see child guidance counselling services for many different reasons.
      Behavioural problems or rather enraged or aggressive behaviour of children and
      adolescents towards their siblings or parents is a frequent issue in counselling
      practice. The current article takes a closer look at the range of problems around
      defiance, anger and aggression from a developmental and systemic point of view.
      The meaning of these negative affects within the family system is elaborated.
      Empirical studies show a clear connection between children's problem behaviour
      and frequent and destructive interparental conflict. So called spill-over-effects
      play a crucial role in explaining this connection. From a systemic perspective
      thus the child is seen as a symptom carrier, which shifts the focus of
      counselling on the interaction between parents as well. Consequently, family
      therapeutic sessions on the couple level are often indicated. Do parents succeed
      in constructively solving their conflicts, typically the aggressive behaviour of
      the children is reduced, too. On the basis of a compound single case such a
      process is illustrated. 

PMID- 25609394
TI  - [Psychotherapeutically-Systemic Acting in the Integrated Family Counseling
      Presented by the Example of Child-Centered Educational Counseling].
AB  - The article gives an insight into the practice of Integrated Family Counseling
      and identifies their interfaces with psychotherapeutic approaches. The example of
      the child-centered educational counseling shows how consultancy, systemic and
      psychotherapeutic interventions interact in order to meet the parents educational
      needs defined by the parents. The first part of the article explains the term of
      Integrated Family Counseling, differentiates the various substantive areas of
      work and outlines the systematic attitude. The second part describes the
      psychotherapy-systemic action in the child-centered educational counseling from
      the perspective of the practice. Main priorities in the course of counseling,
      including cause-related behavioral and developmental diagnostics, play therapy
      intervention and parental involvement are presented. Here the systemic approach,
      major methodological elements as well as their effects are pointed up. The third
      part is devoted to the reflection of the relationship between counseling and
      psychotherapy. It becomes clear that in particular the intended effectiveness of
      an intervention determines their methodological design to a large extent. 

PMID- 25609398
TI  - Economic evaluations with agent-based modelling: an introduction.
AB  - Agent-based modelling (ABM) is a relatively new technique, which overcomes some
      of the limitations of other methods commonly used for economic evaluations. These
      limitations include linearity, homogeneity and stationarity. Agents in ABMs are
      autonomous entities, who interact with each other and with the environment. ABMs
      provide an inductive or 'bottom-up' approach, i.e. individual-level behaviours
      define system-level components. ABMs have a unique property to capture emergence
      phenomena that otherwise cannot be predicted by the combination of individual
      level interactions. In this tutorial, we discuss the basic concepts and important
      features of ABMs. We present a case study of an application of a simple ABM to
      evaluate the cost effectiveness of screening of an infectious disease. We also
      provide our model, which was developed using an open-source software program,
      NetLogo. We discuss software, resources, challenges and future research
      opportunities of ABMs for economic evaluations. 

PMID- 25609399
TI  - UV-visible spectroscopy of macrocyclic alkyl, nitrosyl and halide complexes of
      cobalt and rhodium. Experiment and calculation.
AB  - Transition metal complexes (NH3)5CoX(2+) (X = CH3, Cl) and L(H2O)MX(2+), where M
      = Rh or Co, X = CH3, NO, or Cl, and L is a macrocyclic N4 ligand are examined by
      both experiment and computation to better understand their electronic spectra and
      associated photochemistry. Specifically, irradiation into weak visible bands of
      nitrosyl and alkyl complexes (NH3)5CoCH3(2+) and L(H2O)M(III)X(2+) (X = CH3 or
      NO) leads to photohomolysis that generates the divalent metal complex and CH3 or
      NO, respectively. On the other hand, when X = halide or NO2, visible light
      photolysis leads to dissociation of X(-) and/or cis/trans isomerization.
      Computations show that visible bands for alkyl and nitrosyl complexes involve
      transitions from M-X bonding orbitals and/or metal d orbitals to M-X antibonding
      orbitals. In contrast, complexes with X = Cl or NO2 exhibit only d-d bands in the
      visible, so that homolytic cleavage of the M-X bond requires UV photolysis. UV
      Vis spectra are not significantly dependent on the structure of the equatorial
      ligands, as shown by similar spectral features for (NH3)5CoCH3(2+) and
      L(1)(H2O)CoCH3(2+). 

PMID- 25609401
TI  - Artificial gametes: a systematic review of biological progress towards clinical
      application.
AB  - BACKGROUND: Recent progress in the formation of artificial gametes, i.e. gametes
      generated by manipulation of their progenitors or of somatic cells, has led to
      scientific and societal discussion about their use in medically assisted
      reproduction (MAR). Artificial gametes could potentially help infertile men and
      women but also post-menopausal women and gay couples conceive genetically related
      children. This systematic review aimed to provide insight in the progress of
      biological research towards clinical application of artificial gametes. METHODS:
      The electronic database 'Medline/Pubmed' was systematically searched with medical
      subject heading (MesH) terms, and reference lists of eligible studies were hand
      searched. Studies in English between January 1970 and December 2013 were selected
      based on meeting a priori defined starting- and end-points of gamete development,
      including gamete formation, fertilization and the birth of offspring. For each
      biologically plausible method to form artificial gametes, data were extracted on
      the potential to generate artificial gametes that might be used to achieve
      fertilization and to result in the birth of offspring in animals and humans.
      RESULTS: The systematic search yielded 2424 articles, and 70 studies were
      included after screening. In animals, artificial sperm and artificial oocytes
      generated from germline stem cells (GSCs), embryonic stem cells (ESCs) and
      induced pluripotent stem cells (iPSCs) have resulted in the birth of viable
      offspring. Also in animals, artificial sperm and artificial oocytes have been
      generated from somatic cells directly, i.e. without documentation of intermediate
      stages of stem- or germ cell development or (epi)genetic status. Finally,
      although the subsequent embryos showed hampered development, haploidization by
      transplantation of a somatic cell nucleus into an enucleated donor oocyte has led
      to fertilized artificial oocytes. In humans, artificial sperm has been generated
      from ESCs and iPSCs. Artificial human oocytes have been generated from GSCs, ESCs
      and somatic cells (without documentation of intermediate stages of stem- or germ
      cell development). Fertilization of a human artificial oocyte after
      haploidization by transplantation of a somatic cell nucleus into an enucleated
      donor oocyte was also reported. Normal developmental potential, epigenetic and
      genetic stability and birth of children has not been reported following the use
      of human artificial gametes. In animals, artificial oocytes from a male have been
      created and fertilized and artificial sperm from a female has been fertilized and
      has resulted in the birth of viable offspring. In humans, artificial sperm has
      been generated from female iPSCs. To date, no study has reported the birth of
      human offspring from artificial gametes. CONCLUSION: Our systematic review of the
      literature indicated that in animals live births have already been achieved using
      artificial gametes of varying (cell type) sources. Although experimental
      biological research is progressing steadily towards future clinical application,
      data on functionality, safety and efficiency of (human) artificial gametes are
      still preliminary. Although defining artificial gametes by start- and end-points
      limited the number of included studies, the search resulted in a clear overview
      of the subject. Clinical use of artificial gametes would expand the treatment
      possibilities of MAR and would have implications for society. Before potential
      clinical use, the societal and ethical implications of artificial gametes should
      be reflected on.

PMID- 25609400
TI  - Glibenclamide, metformin, and insulin for the treatment of gestational diabetes:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: To summarize short term outcomes in randomized controlled trials
      comparing glibenclamide or metformin versus insulin or versus each other in women
      with gestational diabetes requiring drug treatment. DESIGN: Systematic review and
      meta-analysis. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized controlled
      trials that fulfilled all the following: (1) published as full text; (2)
      addressed women with gestational diabetes requiring drug treatment; (3) compared
      glibenclamide v insulin, metformin v insulin, or metformin v glibenclamide; and
      (4) provided information on maternal or fetal outcomes. DATA SOURCES: Medline,
      CENTRAL, and Embase were searched up to 20 May 2014. OUTCOMES MEASURES: We
      considered 14 primary outcomes (6 maternal, 8 fetal) and 16 secondary (5
      maternal, 11 fetal) outcomes. RESULTS: We analyzed 15 articles, including 2509
      subjects. Significant differences for primary outcomes in glibenclamide v insulin
      were obtained in birth weight (mean difference 109 g (95% confidence interval
      35.9 to 181)), macrosomia (risk ratio 2.62 (1.35 to 5.08)), and neonatal
      hypoglycaemia (risk ratio 2.04 (1.30 to 3.20)). In metformin v insulin,
      significance was reached for maternal weight gain (mean difference -1.14 kg (
      2.22 to -0.06)), gestational age at delivery (mean difference -0.16 weeks (-0.30
      to -0.02)), and preterm birth (risk ratio 1.50 (1.04 to 2.16)), with a trend for
      neonatal hypoglycaemia (risk ratio 0.78 (0.60 to 1.01)). In metformin v
      glibenclamide, significance was reached for maternal weight gain (mean difference
      -2.06 kg (-3.98 to -0.14)), birth weight (mean difference -209 g (-314 to -104)),
      macrosomia (risk ratio 0.33 (0.13 to 0.81)), and large for gestational age
      newborn (risk ratio 0.44 (0.21 to 0.92)). Four secondary outcomes were better for
      metformin in metformin v insulin, and one was worse for metformin in metformin v
      glibenclamide. Treatment failure was higher with metformin than with
      glibenclamide. CONCLUSIONS: At short term, in women with gestational diabetes
      requiring drug treatment, glibenclamide is clearly inferior to both insulin and
      metformin, while metformin (plus insulin when required) performs slightly better
      than insulin. According to these results, glibenclamide should not be used for
      the treatment of women with gestational diabetes if insulin or metformin is
      available.Systematic review registration NCT01998113.

PMID- 25609402
TI  - Potential consequences of clinical application of artificial gametes: a
      systematic review of stakeholder views.
AB  - BACKGROUND: Recent progress in the formation of artificial gametes, i.e. gametes
      generated from progenitors or somatic cells, has led to scientific and societal
      discussion about their use in medically assisted reproduction. In animals, live
      births have already been achieved using artificial gametes of varying (cell type)
      sources and biological research seems to be progressing steadily toward clinical
      application in humans. Artificial gametes could potentially help not only
      infertile heterosexual couples of reproductive age of which one or both partners
      lacks functional gametes, but also post-menopausal women and same-sex couples, to
      conceive a child who will be genetically related to them. But as clinical
      application of these new technologies may have wider societal consequences, a
      proactive consideration of the possible impact seems timely and important. This
      review aims to contribute to this by providing a systematic overview of the
      potential consequences of clinical application of artificial gametes anticipated
      by different stakeholders. METHODS: The electronic database 'Medline/Pubmed' was
      systematically searched with medical subject heading terms (MesH) for articles
      published in English between January 1970 and December 2013. Articles were
      selected based on eligibility and reference lists of eligible studies were hand
      searched. The reported potential consequences of clinical application of
      artificial gametes were extracted from the articles and were grouped into
      categories by content analysis. Per category, we noted which stakeholders
      referred to which potential consequences, based on author affiliations and, if
      applicable, study participants. RESULTS: The systematic search yielded 2424
      articles, and 84 studies were included after screening. Nine positive
      consequences, 21 specific consequences requiring consideration and 22
      recommendations referring to clinical application of artificial gametes were
      documented. All positive consequences, consequences requiring consideration and
      recommendations could be categorized under the following eight objectives to be
      safeguarded during clinical application of artificial gametes: (i) timing the
      implementation of new treatments correctly, (ii) meeting 'plausible demands of
      patients', (iii) improving and safeguarding public health, (iv) promoting the
      progress of medical science in the interest of future patients, (v) providing
      treatments that are morally acceptable for the general public, (vi) controlling
      medical practice, (vii) offering treatments that allow acquisition of informed
      consent and (viii) funding treatments fairly. Professionals specialized in
      biomedical science, science journalists and professionals specialized in ethics
      all addressed these eight objectives on artificial gametes, whereas professionals
      specialized in law or political science addressed seven objectives. Although one
      study reported on the perspective of parents of under-aged patients on three
      objectives, the perspectives of patients themselves were not reported by the
      reviewed literature. CONCLUSION: Of course, clinical introduction of artificial
      gametes should only be considered on the basis of reassuring outcomes of
      appropriate preclinical effectiveness and safety studies. In addition, potential
      users' views on the desirability and acceptability of artificial gametes should
      be studied before clinical introduction. A societal debate including all
      stakeholders is needed to determine the relative importance of all arguments in
      favor of and against the introduction of artificial gametes into clinical
      practice. More broadly, establishing pre-implementation processes for new medical
      techniques is relevant for all fields of medicine.

PMID- 25609403
TI  - Trained innate immunity as a mechanistic link between sepsis and atherosclerosis.

PMID- 25609404
TI  - COI barcode based species-specific primers for identification of five species of
      stored-product pests from genus Cryptolestes (Coleoptera: Laemophloeidae).
AB  - Flat grain beetles of the genus Cryptolestes (Coleoptera: Laemophloeidae) are one
      of the economically most important stored-product pests which feed on many kinds
      of agricultural products, especially grains. Nine of more than 40 described
      Cryptolestes species are recognized as stored-product pests and two of the pest
      species have a cosmopolitan distribution. Given the rapid growth in global trade
      of food products, ecological barriers to the spread of pests are easily overcome.
      Therefore, development of reliable systems for routine quarantine inspection and
      early infestation detection is vital. In the present study, we established a new
      rapid and accurate cytochrome c oxidase subunit I-based system for molecular
      identification of five common stored-product Cryptolestes species, namely,
      Cryptolestes capensis, Cryptolestes ferrugineus, Cryptolestes pusilloides,
      Cryptolestes pusillus and Cryptolestes turcicus. Five species-specific primer
      pairs for traditional uniplex polymerase chain reaction assay are described and
      their specificity and sensitivity for the identification process is evaluated
      using larval samples of 12 different populations from three continents (Asia,
      Europe and North America). 

PMID- 25609405
TI  - The influence of optimism on functionality after total hip replacement surgery.
AB  - Among other factors, optimism has been shown to significantly influence the
      course of some diseases (cancer, HIV, coronary heart disease). This study
      investigated whether optimism of a patient before a total hip replacement can
      predict the functionality of the lower limbs 3 and 6 months after surgery. A
      total of 325 patients took part in the study (age: 58.7 years; w: 55%). The
      functionality was measured with the Western Ontario and McMaster Universities
      arthrosis index, and optimism with the Life Orientation Test. To analyse the
      influences of age, gender and optimism, general linear models were calculated. In
      optimistic patients, functionality improved significantly over time. The study
      showed a clear influence of dispositional optimism on the recovery after total
      hip replacement in the first 3 months after surgery.

PMID- 25609406
TI  - The physical sacrifice of thinking: Investigating the relationship between
      thinking and physical activity in everyday life.
AB  - Physical activity level is an important contributor to overall human health and
      obesity. Research has shown that humans possess a number of traits that influence
      their physical activity level including social cognition. We examined whether the
      trait of "need for cognition" was associated with daily physical activity levels.
      We recruited individuals who were high or low in need for cognition and measured
      their physical activity level in 30-second epochs over a 1-week period. The
      overall findings showed that low-need-for-cognition individuals were more
      physically active, but this difference was most pronounced during the 5-day work
      week and lessened during the weekend.

PMID- 25609407
TI  - Visual weight status misperceptions of men: Why overweight can look like a
      healthy weight.
AB  - Overweight men often underestimate their weight status. Here, we examine whether
      underestimation occurs when visually judging the weight status of men and whether
      exposure to heavier body weights may be a cause of visual underestimation of male
      weight status. Participants systematically underestimated the weight status of
      overweight and obese men (Study 1) and participants reporting more frequent
      exposure to heavy male body weights were most likely to underestimate (Study 2).
      Experimental exposure to different body weights influenced underestimation of
      weight status (Study 3). Frequent exposure to heavier body weights may cause
      visual underestimation of the weight status of overweight men.

PMID- 25609408
TI  - Happiness and social determinants across age cohorts in Taiwan.
AB  - The purpose of this study was to examine happiness and social determinants across
      age cohorts in Taiwan. The data were obtained from the 2011 Taiwan Social Change
      Survey (aged 18 +, n = 2,199). The social determinants of happiness included
      socioeconomic status and social connection. Happiness was not different across
      the age groups. Receiving less family support, less formal support, more social
      trust and more control over life were significant for the younger group. Being
      married and having more social participation were significant for the middle
      aged. Receiving less family support and having a higher economic status were
      significant for the older group.

PMID- 25609410
TI  - An automated programmable platform enabling multiplex dynamic stimuli delivery
      and cellular response monitoring for high-throughput suspension single-cell
      signaling studies.
AB  - Cell signaling events are orchestrated by dynamic external biochemical cues. By
      rapidly perturbing cells with dynamic inputs and examining the output from these
      systems, one could study the structure and dynamic properties of a cellular
      signaling network. Conventional experimental techniques limit the implementation
      of these systematic approaches due to the lack of sophistication in manipulating
      individual cells and the fluid microenvironment around them; existing
      microfluidic technologies thus far are mainly targeting adherent cells. In this
      paper we present an automated platform to interrogate suspension cells with
      dynamic stimuli while simultaneously monitoring cellular responses in a high
      throughput manner at single-cell resolution. We demonstrate the use of this
      platform in an experiment to measure Jurkat T cells in response to distinct
      dynamic patterns of stimuli; we find cells exhibit highly heterogeneous responses
      under each stimulation condition. More interestingly, these cells act as low-pass
      filters, only entrained to the low frequency stimulus signals. We also
      demonstrate that this platform can be easily programmed to actively generate
      arbitrary dynamic signals. We envision our platform to be useful in other
      contexts to study cellular signaling dynamics, which may be difficult using
      conventional experimental methods. 

PMID- 25609411
TI  - Metabolomics for rheumatic diseases: has the time come?

PMID- 25609412
TI  - Association of hyperlipidaemia, inflammation and serological status and coronary
      heart disease among patients with rheumatoid arthritis: data from the National
      Veterans Health Administration.
AB  - OBJECTIVE: To examine the association of serum lipids, inflammation and
      seropositivity on coronary heart disease (CHD) and stroke in patients with
      rheumatoid arthritis (RA). METHODS: The incidence of hospitalised myocardial
      infarction (MI) or stroke was calculated in a cohort of patients with RA
      receiving care within the national Veterans Health Administration from 1998 to
      2011. Cox proportional hazard models were used to examine the association between
      these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR) as time-varying variables, divided into quintiles.
      RESULTS: There were 37,568 patients with RA in the cohort with mean age of 63
      years (SD 12.1); 90% were men. There was a no clear association between LDL-C and
      CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (>=54 mg/dL) was
      inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and
      stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26
      mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI
      and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had
      an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for
      stroke. The association between MI was significant for RA seropositivity
      (HR=1.23, 95% CI 1.03 to 1.48). CONCLUSIONS: In this predominantly older male RA
      cohort, there was no clear association between LDL-C and CHD, whereas higher HDL
      C was inversely associated with MI and stroke. CRP and ESR were similarly
      associated with increase MI risk and stroke, reflecting the prominent role of
      inflammation in CHD risk in RA.

PMID- 25609413
TI  - Rapid induction of clinical remission by low-dose interleukin-2 in a patient with
      refractory SLE.

PMID- 25609414
TI  - Impact of left ventricular hypertrophy on troponin release during acute
      myocardial infarction: new insights from a comprehensive translational study.
AB  - BACKGROUND: Biomarkers are frequently used to estimate infarct size (IS) as an
      endpoint in experimental and clinical studies. Here, we prospectively studied the
      impact of left ventricular (LV) hypertrophy (LVH) on biomarker release in
      clinical and experimental myocardial infarction (MI). METHODS AND RESULTS: ST
      segment elevation myocardial infarction (STEMI) patients (n=140) were monitored
      for total creatine kinase (CK) and cardiac troponin I (cTnI) over 72 hours
      postinfarction and were examined by cardiac magnetic resonance (CMR) at 1 week
      and 6 months postinfarction. MI was generated in pigs with induced LVH (n=10) and
      in sham-operated pigs (n=8), and serial total CK and cTnI measurements were
      performed and CMR scans conducted at 7 days postinfarction. Regression analysis
      was used to study the influence of LVH on total CK and cTnI release and IS
      estimated by CMR (gold standard). Receiver operating characteristic (ROC) curve
      analysis was performed to study the discriminatory capacity of the area under the
      curve (AUC) of cTnI and total CK in predicting LV dysfunction. Cardiomyocyte cTnI
      expression was quantified in myocardial sections from LVH and sham-operated pigs.
      In both the clinical and experimental studies, LVH was associated with
      significantly higher peak and AUC of cTnI, but not with differences in total CK.
      ROC curves showed that the discriminatory capacity of AUC of cTnI to predict LV
      dysfunction was significantly worse for patients with LVH. LVH did not affect the
      capacity of total CK to estimate IS or LV dysfunction. Immunofluorescence
      analysis revealed significantly higher cTnI content in hypertrophic
      cardiomyocytes. CONCLUSIONS: Peak and AUC of cTnI both significantly overestimate
      IS in the presence of LVH, owing to the higher troponin content per
      cardiomyocyte. In the setting of LVH, cTnI release during STEMI poorly predicts
      postinfarction LV dysfunction. LV mass should be taken into consideration when IS
      or LV function are estimated by troponin release.

PMID- 25609415
TI  - Prospective national study of the prevalence, incidence, management and outcome
      of a large contemporary cohort of patients with incident non-valvular atrial
      fibrillation.
AB  - BACKGROUND: There are few studies of atrial fibrillation (AF) outside of North
      America or Europe. The aim of the present study was to assess the prevalence,
      incidence, management and outcomes of patients with new atrial fibrillation, in a
      large contemporary cohort (2004-2012) of adult patients. METHODS AND RESULTS: The
      Clalit Health Services (CHS) computerized database of 2 420 000 adults, includes
      data of community clinic visits, hospital discharge records, medical diagnoses,
      medications, medical interventions, and laboratory test results. The prevalence
      of AF on January 1, 2004 was 71 644 (3%). Prevalence and incidence of AF
      increased with age and was higher in men versus women. During the study period
      (2004-2012) 98 811 patients developed new non-valvular AF (mean age -72, 50%
      women, 46% with cardiovascular disease, 6% with prior stroke). The rate of
      persistent warfarin use (dispensed for >3 months in a calendar year) was low
      (25.7%) and it increased with increasing stroke risk score. Individual Time in
      Therapeutic Range (TTR) among warfarin users was 42%. The incidence rate of
      ischemic stroke and death increased with age. The rate of stroke increased from 2
      per 1000 person years in patients with CHA(2)DS(2)_VASC SCORE of 0, to 58 per
      1000 person years in those with a score of 9. CONCLUSIONS: In the present study
      the prevalence and incidence of AF, stroke, and death were comparable to those
      reported in Europe and North America. The low use of anticoagulation calls for
      measures to increase adherence to current treatment recommendations in order to
      improve outcomes.

PMID- 25609417
TI  - Prospective community screening for aortic conditions--true incidence or just a
      better guess?

PMID- 25609416
TI  - Risk profiles for aortic dissection and ruptured or surgically treated aneurysms:
      a prospective cohort study.
AB  - BACKGROUND: Community screening to guide preventive interventions for acute
      aortic disease has been recommended in high-risk individuals. We sought to
      prospectively assess risk factors in the general population for aortic dissection
      (AD) and severe aneurysmal disease in the thoracic and abdominal aorta. METHODS
      AND RESULTS: We studied the incidence of AD and ruptured or surgically treated
      aneurysms in the abdominal (AAA) or thoracic aorta (TAA) in 30 412 individuals
      without diagnosis of aortic disease at baseline from a contemporary, prospective
      cohort of middle-aged individuals, the Malmo Diet and Cancer study. During up to
      20 years of follow-up (median 16 years), the incidence rate per 100 000 patient
      years at risk was 15 (95% CI 11.7 to 18.9) for AD, 27 (95% CI 22.5 to 32.1) for
      AAA, and 9 (95% CI 6.8 to 12.6) for TAA. The acute and in-hospital mortality was
      39% for AD, 34% for ruptured AAA, and 41% for ruptured TAA. Hypertension was
      present in 86% of individuals who subsequently developed AD, was strongly
      associated with incident AD (hazard ratio [HR] 2.64, 95% CI 1.33 to 5.25), and
      conferred a population-attributable risk of 54%. Hypertension was also a risk
      factor for AAA with a smaller effect. Smoking (HR 5.07, 95% CI 3.52 to 7.29) and
      high apolipoprotein B/A1 ratio (HR 2.48, 95% CI 1.73 to 3.54) were strongly
      associated with AAA and conferred a population-attributable risk of 47% and 25%,
      respectively. Smoking was also a risk factor for AD and TAA with smaller effects.
      CONCLUSIONS: This large prospective study identified distinct risk factor
      profiles for different aortic diseases in the general population. Hypertension
      accounted for more than half of the population risk for AD, and smoking for half
      of the population risk of AAA.

PMID- 25609419
TI  - Evidence of "new hot spots" from determining the nonlinear optical behavior of
      materials: mechanistic studies of the vanadium borate crystal, Na3VO2B6O11.
AB  - A novel mechanism for the nonlinear optical (NLO) effects of vanadium borate
      crystals, Na3VO2B6O11 (NVB), with distorted VO4 groups was investigated. A
      comprehensive analysis of the structure-property relationship was performed by
      combining the experimental measurements, the electronic structures calculations,
      the SHG-weighted electron density and the real-space atom-contribution analysis
      to yield the linear and nonlinear optical properties. The contribution of a
      (VO4)(3-) anionic group to the second harmonic generation (SHG) response was more
      pronounced than that of the (BO3)(3-) anionic group, which plays a virtual role
      in the SHG effects in NVB. The anionic (BO3)(3-) groups make dominant
      contributions to the birefringence, whereas the contribution of the V(5+) cations
      to these linear optical effects is negligible. 

PMID- 25609418
TI  - Intestinal and neuronal myenteric adaptations in the small intestine induced by a
      high-fat diet in mice.
AB  - BACKGROUND: The prevalence of obesity has increased at alarming rates,
      particularly because of the increased consumption of high-fat diets (HFDs). The
      influence of HFDs on intrinsic innervation and the intestinal wall has not been
      fully characterized. The aim of this study was to investigate the morpho
      quantitative aspects of myenteric neurons and the wall of the small intestine in
      mice fed a HFD. METHODS: Swiss mice were fed a HFD (59% kcal from fat) or
      standard chow (9% Kcal from fat) for 8 weeks. Segments of the duodenum, jejunum,
      and ileum were subjected to histological processing for morpho-quantitative
      examination of the intestinal wall and mucosal cells, and immunohistochemistry
      was performed to evaluate myenteric neurons. The data for each segment were
      compared between the groups using an unpaired Student's t-test or an equivalent
      nonparametric test. RESULTS: The HFD increased body weight and visceral fat and
      decreased the length of the small intestine and the circumference of the ileum.
      In the duodenum, the HFD increased the density of the nitrergic subpopulation and
      decreased the area of nitrergic neurons and vasoactive intestinal peptide (VIP)
      varicosities. In the jejunum, the density of the nitrergic subpopulation was
      increased and the neuronal areas of the general population, nitrergic
      subpopulation and (VIP) varicosities were reduced. In the ileum, the density of
      the general population and nitrergic subpopulation were increased and the
      neuronal areas of the general population, nitrergic subpopulation and (VIP)
      varicosities were reduced. The morphometric parameters of the villi, crypts,
      muscular layer and total wall generally increased in the duodenum and jejunum and
      decreased in the ileum. In the duodenum and jejunum, the HFD promoted a decreased
      in the proportion of intraepithelial lymphocytes. In the ileum, the proportion of
      intraepithelial lymphocytes and goblet cells reduced, and the enteroendocrine
      cells increased. CONCLUSIONS: The high-fat diet induces changes in the myenteric
      innervation of the small intestine, intestinal wall and mucosal cells responsible
      for the secretion of hormones and maintenance of the protective intestinal
      barrier. The morpho-quantitative data provide a basis for further studies to
      clarify the influence of HFD in the motility, digestive and absorptive capacity,
      and intestinal barrier.

PMID- 25609420
TI  - Treatment variation in patients diagnosed with early stage breast cancer in
      Alberta from 2002 to 2010: a population-based study.
AB  - BACKGROUND: Breast-conserving surgery (BCS) followed by radiotherapy is generally
      the preferred treatment for women diagnosed with early stage breast cancer. This
      study aimed to investigate the proportion of patients who receive BCS versus
      mastectomy and post-BCS radiotherapy, and explore factors associated with receipt
      of these treatments in Alberta, Canada. METHODS: A retrospective population-based
      study was conducted that including all patients surgically treated with stage I
      III breast cancer diagnosed in Alberta from 2002-2010. Clinical characteristics,
      treatment information and patient age at diagnosis were collected from the
      Alberta Cancer Registry. Log binomial multiple regression was used to calculate
      stage-specific relative risk estimates of receiving BCS and post-BCS
      radiotherapy. RESULTS: Of the 14 646 patients included in the study, 44% received
      BCS, and of those, 88% received post-BCS radiotherapy. The adjusted relative risk
      of BCS was highest in Calgary and lowest in Central Alberta for all disease
      stages. Relative to surgeries performed in Calgary, those performed in Central
      Alberta were significantly less likely to be BCS for stage I (RR = 0.65; 95%
      0.57, 0.72), II (RR = 0.58; 95% 0.49, 0.68), and III (RR = 0.62; 95% CI: 0.37,
      0.95) disease, respectively, adjusting for patient age at diagnosis, clinical and
      treatment characteristics. No significant variation of post-BCS radiotherapy was
      found. CONCLUSIONS: Factors such as region of surgical treatment should not be
      related to the receipt of standard care within a publicly-funded health care
      system. Further investigation is needed to understand the significant geographic
      variation present within the province in order to identify appropriate
      interventions.

PMID- 25609421
TI  - Could low grade bacterial infection contribute to low back pain? A systematic
      review.
AB  - BACKGROUND: Recently, there has been both immense interest and controversy
      regarding a randomised, controlled trial which showed antibiotics to be effective
      in the treatment of chronic low back pain (disc herniation with Modic Type 1
      change). While this research has the potential to result in a paradigm shift in
      the treatment of low back pain, several questions remain unanswered. This
      systematic review aims to address these questions by examining the role of
      bacteria in low back pain and the relationship between bacteria and Modic change.
      METHODS: We conducted electronic searches of MEDLINE and EMBASE and included
      studies that examined the relationship between bacteria and back pain or Modic
      change. Studies were rated based on their methodological quality, a best-evidence
      synthesis was used to summarise the results, and Bradford Hill's criteria were
      used to assess the evidence for causation. RESULTS: Eleven studies were
      identified. The median (range) age and percentage of female participants was 44.7
      (41-46.4) years and 41.5% (27-59%), respectively, and in 7 of the 11 studies
      participants were diagnosed with disc herniation. Nine studies examined the
      presence of bacteria in spinal disc material and all identified bacteria, with
      the pooled estimate of the proportion with positive samples being 34%.
      Propionibacterium acnes was the most prevalent bacteria, being present in 7 of
      the 9 studies, with median (minimum, maximum) 45.0% (0-86.0) of samples positive.
      The best evidence synthesis found moderate evidence for a relationship between
      the presence of bacteria and both low back pain with disc herniation and Modic
      Type 1 change with disc herniation. There was modest evidence for a cause-effect
      relationship. CONCLUSIONS: We found that bacteria were common in the spinal disc
      material of people undergoing spinal surgery. There was moderate evidence for a
      relationship between the presence of bacteria and both low back pain with disc
      herniation and Modic Type 1 change associated with disc herniation and modest
      evidence for causation. However, further work is needed to determine whether
      these organisms are a result of contamination or represent low grade infection of
      the spine which contributes to chronic low back pain.

PMID- 25609422
TI  - AMPKalpha is critical for enhancing skeletal muscle fatty acid utilization during
      in vivo exercise in mice.
AB  - The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal
      muscle with contraction/exercise is unresolved. Using a mouse model lacking both
      AMPKalpha1 and -alpha2 in skeletal muscle specifically (mdKO), we hypothesized
      that FA utilization would be impaired in skeletal muscle. AMPKalpha mdKO mice
      displayed normal respiratory exchange ratio (RER) when fed chow or a high-fat
      diet, or with prolonged fasting. However, in vivo treadmill exercise at the same
      relative intensity induced a higher RER in AMPKalpha mdKO mice compared to wild
      type (WT = 0.81 +/- 0.01 (sem); mdKO = 0.87 +/- 0.02 (sem); P < 0.01), indicating
      a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation
      was impaired in AMPKalpha mdKO muscle, suggesting that the increased RER during
      exercise originated from decreased skeletal muscle FA oxidation. A decreased
      muscle protein expression of CD36 (cluster of differentiation 36) and FABPpm
      (plasma membrane fatty acid binding protein) (by ~17-40%), together with fully
      abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237)
      phosphorylation during contraction/exercise in AMPKalpha mdKO mice, may impair FA
      transport capacity and FA transport protein translocation to sarcolemma,
      respectively. AMPKalpha is thus required for normal FA metabolism during exercise
      and muscle contraction.

PMID- 25609423
TI  - Low CO2 permeability of cholesterol-containing liposomes detected by stopped-flow
      fluorescence spectroscopy.
AB  - Here we ask the following: 1) what is the CO2 permeability (Pco2) of unilamellar
      liposomes composed of l-alpha-phosphatidylcholine (PC)/l-alpha-phosphatidylserine
      (PS) = 4:1 and containing cholesterol (Chol) at levels often occurring in
      biologic membranes (50 mol%), and 2) does incorporation of the CO2 channel
      aquaporin (AQP)1 cause a significant increase in membrane Pco2? Presently, a
      drastic discrepancy exists between the answers to these two questions obtained
      from mass-spectrometric (18)O-exchange measurements (Chol reduces Pco2 100-fold,
      AQP1 increases Pco2 10-fold) vs. from stopped-flow approaches observing CO2
      uptake (no effects of either Chol or AQP1). A novel theory of CO2 uptake by
      vesicles predicts that in a stopped-flow apparatus this fast process can only be
      resolved temporally and interpreted quantitatively, if 1) a very low CO2 partial
      pressure (pCO2) is used (e.g., 18 mmHg), and 2) intravesicular carbonic anhydrase
      (CA) activity is precisely known. With these prerequisites fulfilled, we find by
      stopped-flow that 1) Chol-containing vesicles possess a Pco2 = 0.01cm/s, and Chol
      free vesicles exhibit ~1 cm/s, and 2) the Pco2 of 0.01 cm/s is increased >= 10
      fold by AQP1. Both results agree with previous mass-spectrometric results and
      thus resolve the apparent discrepancy between the two techniques. We confirm that
      biologic membranes have an intrinsically low Pco2 that can be raised when
      functionally necessary by incorporating protein-gas channels such as AQP1.

PMID- 25609425
TI  - Histone H3K9 demethylase JMJD1A modulates hepatic stellate cells activation and
      liver fibrosis by epigenetically regulating peroxisome proliferator-activated
      receptor gamma.
AB  - As a central event in liver fibrogenesis, hepatic stellate cell (HSC)
      transdifferentiation involves loss of regulation by adipogenic transcription
      factors such as peroxisome proliferator-activated receptor gamma; (PPARgamma),
      which is epigenetically silenced during HSC activation. We hypothesized that
      JMJD1A, an H3K9 demethylase involved in adipogenic metabolism, could regulate
      PPARgamma. In human HSC cell line, rat primary HSCs, and carbontetrachloride
      induced mouse liver fibrogenesis model, we down-regulated the expression of
      JMJD1A using small interfering or short hairpin RNAs, and overexpressed its wild
      type and mutant. We analyzed the effects of JMJD1A manipulation on the histone di
      methyl-H3K9 (H3k9me2) status of PPARgamma gene and the expression of PPARgamma
      and fibrosis markers using chromatin immunoprecipitation, real-time quantitative
      RT-PCR and Western blot, and also investigated the in vitro and in vivo
      consequences on liver fibrosis and necrosis by Masson or hematoxylin-eosin
      staining, respectively. JMJD1A knockdown in HSCs correlated with reinforced
      H3K9me2 in the PPARgamma gene promoter, and its down-regulation in both mRNA and
      protein led to increased expression of fibrosis markers, which could be
      consistently rescued by JMJD1A overexpression. Jmjd1a knockdown in situ resulted
      in significantly increased expression of alpha-smooth muscle actin (P = 0.005)
      and Col1a (P = 0.036), strengthened production of collagens (P = 0.028), and
      remarkably enhanced necrosis (P = 0.007) 4 weeks after treatment. This study
      suggests JMJD1A as a novel epigenetic regulator that modulates HSC activation and
      liver fibrosis through targeting PPARgamma gene expression.

PMID- 25609426
TI  - Exercise increases pancreatic beta-cell viability in a model of type 1 diabetes
      through IL-6 signaling.
AB  - Type 1 diabetes (T1D) is provoked by an autoimmune assault against pancreatic
      beta cells. Exercise training enhances beta-cell mass in T1D. Here, we
      investigated how exercise signals beta cells in T1D condition. For this, we used
      several approaches. Wild-type and IL-6 knockout (KO) C57BL/6 mice were exercised.
      Afterward, islets from control and trained mice were exposed to inflammatory
      cytokines (IL-1beta plus IFN-gamma). Islets from control mice and beta-cell lines
      (INS-1E and MIN6) were incubated with serum from control or trained mice or
      medium obtained from 5-aminoimidazole-4 carboxamide1-beta-d-ribofuranoside
      (AICAR)-treated C2C12 skeletal muscle cells. Subsequently, islets and beta cells
      were exposed to IL-1beta plus IFN-gamma. Proteins were assessed by
      immunoblotting, apoptosis was determined by DNA-binding dye propidium iodide
      fluorescence, and NO(*) was estimated by nitrite. Exercise reduced 25, 75, and
      50% of the IL-1beta plus IFN-gamma-induced iNOS, nitrite, and cleaved caspase-3
      content, respectively, in pancreatic islets. Serum from trained mice and medium
      from AICAR-treated C2C12 cells reduced beta-cell death, induced by IL-1beta plus
      IFN-gamma treatment, in 15 and 38%, respectively. This effect was lost in samples
      treated with IL-6 inhibitor or with serum from exercised IL-6 KO mice. In
      conclusion, muscle contraction signals beta-cell survival in T1D through IL-6.

PMID- 25609424
TI  - Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the
      ovine fetus.
AB  - Impaired blood-brain barrier function represents an important component of
      hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines
      could contribute to ischemia-related blood-brain barrier dysfunction. IL-6
      increases vascular endothelial cell monolayer permeability in vitro. However,
      contributions of IL-6 to blood-brain barrier abnormalities have not been examined
      in the immature brain in vivo. We generated pharmacologic quantities of ovine
      specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal
      sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs
      were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid,
      blood-brain barrier permeability was quantified using the blood-to-brain transfer
      constant in brain regions, and IL-6, tight junction proteins, and plasmalemma
      vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb
      infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma,
      and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours
      after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in
      blood-brain barrier permeability and modulated tight junction and PLVAP protein
      expression in fetal brain. We conclude that inhibiting the effects of IL-6
      protein with systemic infusions of neutralizing antibodies attenuates ischemia
      related increases in blood-brain barrier permeability by inhibiting IL-6 and
      modulates tight junction proteins after ischemia.

PMID- 25609427
TI  - Modulation of Dhh signaling and altered Sertoli cell function in mice lacking the
      GPR37-prosaposin receptor.
AB  - The mammalian G-protein-coupled receptor 37 (GPR37) is expressed in brain, in
      adult testis, and during the early phase of gonad differentiation. Somatic
      Sertoli cells (SCs) are located within the seminiferous tubules where they
      support the germinal epithelium. An adequate number of SCs is required for the
      complete prepubertal differentiation of germ cells and adult fertility. This
      study shows that Gpr37 and its ligand prosaposin are both postnatally expressed
      by SCs, whose proliferation and maturation are affected in Gpr37-null mutant mice
      during postnatal testicular development. Mutant pups show a delayed timing in
      sperm cell development, with a partial arrest of spermatocytes at the meiotic
      pachytene (e.g., 1.5-fold increase in Gpr37(-/-) P21 pups) and their increased
      apoptosis (e.g., 1.8-fold and 3.5-fold increase in Gpr37(-/-) P21 and adult mice,
      respectively). Mutant adults have reduced testis weight (wild type, 299 +/- 5 mg;
      knockout, 258 +/- 16 mg; P < 0.05) and epididymal sperm count and motility (e.g.,
      1.5-fold and 1.45-fold decrease in Gpr37(-/-) mice, respectively). Lack of Gpr37
      results in the reduction in androgen receptor levels during prepubertal testis
      development, alongside the altered expression of SC maturation markers. It also
      affects the prepubertal testis expression of desert hedgehog (Dhh) mitogenic
      cascade components (Dhh, 1.3-fold increase in Gpr37(-/-) P10 and P21 pups; Gli2,
      1.4-fold and 1.6-fold increase in Gpr37(-/-) P10 and P21 pups, respectively)
      including patched homolog 1 (1.3-fold increase in Gpr37(-/-) P10 and P21 pups),
      which is found localized in prepubertal SCs and is associated with Gpr37 in
      cultured primary SC samples. These results indicate that Gpr37 is a specific
      modulator of murine testis Dhh mitogenic signaling and SC proliferation and
      maturation.

PMID- 25609428
TI  - Leucine-rich repeat kinase 2-sensitive Na+/Ca2+ exchanger activity in dendritic
      cells.
AB  - Gene variants of the leucine-rich repeat kinase 2 (LRRK2) are associated with
      susceptibility to Parkinson's disease (PD). Besides brain and periphery, LRRK2 is
      expressed in various immune cells including dendritic cells (DCs), antigen
      presenting cells linking innate and adaptive immunity. However, the function of
      LRRK2 in the immune system is still incompletely understood. Here, Ca(2+)
      signaling was analyzed in DCs isolated from gene-targeted mice lacking lrrk2
      (Lrrk2(-/-)) and their wild-type littermates (Lrrk2(+/+)). According to Western
      blotting, Lrrk2 was expressed in Lrrk2(+/+) DCs but not in Lrrk2(-/-)DCs.
      Cytosolic Ca(2+) levels ([Ca(2+)]i) were determined utilizing Fura-2 fluorescence
      and whole cell currents to decipher electrogenic transport. The increase of
      [Ca(2+)]i following inhibition of sarcoendoplasmatic Ca(2+)-ATPase with
      thapsigargin (1 uM) in the absence of extracellular Ca(2+) (Ca(2+)-release) and
      the increase of [Ca(2+)]i following subsequent readdition of extracellular Ca(2+)
      (SOCE) were both significantly larger in Lrrk2(-/-) than in Lrrk2(+/+) DCs. The
      augmented increase of [Ca(2+)]i could have been due to impaired Ca(2+) extrusion
      by K(+)-independent (NCX) and/or K(+)-dependent (NCKX) Na(+)/Ca(2+)-exchanger
      activity, which was thus determined from the increase of [Ca(2+)]i,
      (Delta[Ca(2+)]i), and current following abrupt replacement of Na(+) containing
      (130 mM) and Ca(2+) free (0 mM) extracellular perfusate by Na(+) free (0 mM) and
      Ca(2+) containing (2 mM) extracellular perfusate. As a result, both slope and
      peak of Delta[Ca(2+)]i as well as Na(+)/Ca(2+) exchanger-induced current were
      significantly lower in Lrrk2(-/-) than in Lrrk2(+/+) DCs. A 6 or 24 hour
      treatment with the LRRK2 inhibitor GSK2578215A (1 uM) significantly decreased
      NCX1 and NCKX1 transcript levels, significantly blunted Na(+)/Ca(2+)-exchanger
      activity, and significantly augmented the increase of [Ca(2+)]i following Ca(2+)
      release and SOCE. In conclusion, the present observations disclose a completely
      novel functional significance of LRRK2, i.e., the up-regulation of Na(+)/Ca(2+)
      exchanger transcription and activity leading to attenuation of Ca(2+)-signals in
      DCs.

PMID- 25609429
TI  - Dimerization and phosphatase activity of calcyclin-binding protein/Siah-1
      interacting protein: the influence of oxidative stress.
AB  - CacyBP/SIP [calcyclin-binding protein/Siah-1 [seven in absentia homolog 1 (Siah
      E3 ubiquitin protein ligase 1)] interacting protein] is a multifunctional protein
      whose activity includes acting as an ERK1/2 phosphatase. We analyzed dimerization
      of mouse CacyBP/SIP in vitro and in mouse neuroblastoma cell line (NB2a) cells,
      as well as the structure of a full-length protein. Moreover, we searched for the
      CacyBP/SIP domain important for dimerization and dephosphorylation of ERK2, and
      we analyzed the role of dimerization in ERK1/2 signaling in NB2a cells. Cell
      based assays showed that CacyBP/SIP forms a homodimer in NB2a cell lysate, and
      biophysical methods demonstrated that CacyBP/SIP forms a stable dimer in vitro.
      Data obtained using small-angle X-ray scattering supported a model in which
      CacyBP/SIP occupies an anti-parallel orientation mediated by the N-terminal
      dimerization domain. Site-directed mutagenesis established that the N-terminal
      domain is indispensable for full phosphatase activity of CacyBP/SIP. We also
      demonstrated that the oligomerization state of CacyBP/SIP as well as the level of
      post-translational modifications and subcellular distribution of CacyBP/SIP
      change after activation of the ERK1/2 pathway in NB2a cells due to oxidative
      stress. Together, our results suggest that dimerization is important for
      controlling phosphatase activity of CacyBP/SIP and for regulating the ERK1/2
      signaling pathway.

PMID- 25609430
TI  - Molecular and cellular profiles of the resolution phase in a damage-associated
      molecular pattern (DAMP)-mediated peritonitis model and revelation of leukocyte
      persistence in peritoneal tissues.
AB  - Models of microbe-elicited peritonitis have been invaluable to identify
      mechanisms underlying inflammation resolution, but whether resolution mechanisms
      differ from an inflammatory agent to another has not been determined. Thus, we
      analyzed the cellular and molecular components of the resolution phase of non
      microbe-induced inflammation. In thioglycollate (TG)-induced peritonitis,
      resolution started at 12 h (Tmax) and displayed a 22 h resolution interval (Ri).
      During resolution, lipoxin A4, resolvin (Rv) D1 and RvD2, protectin D1 (PD1), and
      maresin 1 (MaR1) were transiently produced while RvD5 was continually generated.
      In addition, docosahexaenoic acid (DHA)-derived mediators were produced to a
      higher extent than in microbial peritonitis. We also investigated leukocyte
      infiltration and clearance in peritoneal tissues surrounding the inflammatory
      site. In the omentum, resolution parameters, neutrophil apoptosis, and
      efferocytosis were similar to those of the peritoneal cavity. However, we noticed
      long-term persistence of M2-polarized macrophages and B-lymphocytes in the
      omentum after TG administration, whereas zymosan injection caused M1/M2
      macrophage and T-lymphocyte persistence regardless of the magnitude of the
      inflammatory response. Our study indicates that some aspects of resolution are
      shaped in a stimulus-specific manner, and it ultimately argues that the tissues
      surrounding the inflammatory site must also be considered to address the
      inflammatory response globally.

PMID- 25609431
TI  - Protein kinase STK25 regulates hepatic lipid partitioning and progression of
      liver steatosis and NASH.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver
      disease, and 10% to 20% of NAFLD patients progress to nonalcoholic
      steatohepatitis (NASH). The molecular pathways controlling progression to
      NAFLD/NASH remain poorly understood. We recently identified serine/threonine
      protein kinase 25 (STK25) as a regulator of whole-body insulin and glucose
      homeostasis. This study investigates the role of STK25 in liver lipid
      accumulation and NASH. Stk25 transgenic mice challenged with a high-fat diet
      displayed a dramatic increase in liver steatosis and hepatic insulin resistance
      compared to wild-type siblings. Focal fibrosis, hepatocellular damage, and
      inflammation were readily seen in transgenic but not wild-type livers. Transgenic
      livers displayed reduced beta-oxidation and triacylglycerol secretion, while
      lipid uptake and synthesis remained unchanged. STK25 was associated with lipid
      droplets, colocalizing with the main hepatic lipid droplet-coating protein
      adipose differentiation-related protein, the level of which was increased 3.8 +/-
      0.7-fold in transgenic livers (P < 0.01), while a key hepatic lipase, adipose
      triacylglycerol lipase, was translocated from the lipid droplets surface to the
      cytoplasm, providing the likely mechanism underlying the effect of STK25. In
      summary, STK25 is a lipid droplet-associated protein that promotes NAFLD through
      control of lipid release from the droplets for beta-oxidation and triacylglycerol
      secretion. STK25 also drives pathogenesis of NASH.

PMID- 25609433
TI  - Of decrements and disorders: assessing impairments in neurodevelopment in
      prospective studies of environmental toxicant exposures.
AB  - Prenatal and early life neurodevelopment is exquisitely sensitive to insult from
      environmental exposures. Identifying the effects of environmental toxicants on
      neurodevelopmental disorders is particularly important from a public health
      perspective because many of these exposures are modifiable and may be targeted
      for intervention. Studying these associations in prospective cohort studies that
      measure quantitative, dimensional traits related to neurodevelopmental disorders,
      using standardized instruments such as psychometric tests or rating scales,
      mitigates many of the challenges that arise when studying clinically diagnosed
      disorders. We consider validity and feasibility impacts resulting from this
      design approach, including: 1) enhanced prospective exposure assessment with high
      quality environmental measures during developmentally relevant windows; 2)
      reduced bias because studies of continuous outcomes do not recruit cases and
      controls and are therefore not vulnerable to control selection bias; 3) enhanced
      statistical power because traits are measured on all individuals in the cohort
      and power is not limited by the number of cases; 4) reduced outcome
      misclassification because measuring quantitative traits avoids lumping together
      individuals with very heterogeneous phenotypes into one category. We use autism
      spectrum disorders (ASD) as an example to illustrate the advantages of this
      approach. Investigating the determinants of neurodevelopmental disorders -
      particularly modifiable determinants such as environmental toxicant exposures -
      is of great public health importance, given the apparent substantial rise of
      disorders like ASD over the past few decades. The use of prospective designs
      measuring quantitative, dimensional traits offers a powerful opportunity to
      provide important clues to the etiology of these disorders and is likely to
      accelerate our understanding of the role of environmental toxicant exposures as
      risk factors. 

PMID- 25609434
TI  - A prospective evaluation of survivorship of asymptomatic degenerative rotator
      cuff tears.
AB  - BACKGROUND: The purpose of this prospective study was to report the long-term
      risks of rotator cuff tear enlargement and symptom progression associated with
      degenerative asymptomatic tears. METHODS: Subjects with an asymptomatic rotator
      cuff tear in one shoulder and pain due to rotator cuff disease in the
      contralateral shoulder enrolled as part of a prospective longitudinal study. Two
      hundred and twenty-four subjects (118 initial full-thickness tears, fifty-six
      initial partial-thickness tears, and fifty controls) were followed for a median
      of 5.1 years. Validated functional shoulder scores were calculated (visual analog
      pain scale, American Shoulder and Elbow Surgeons [ASES], and simple shoulder test
      [SST] scores). Subjects were followed annually with shoulder ultrasonography and
      clinical evaluations. RESULTS: Tear enlargement was seen in 49% of the shoulders,
      and the median time to enlargement was 2.8 years. The occurrence of tear
      enlargement events was influenced by the severity of the final tear type, with
      enlargement of 61% of the full-thickness tears, 44% of the partial-thickness
      tears, and 14% of the controls (p < 0.05). Subject age and sex were not related
      to tear enlargement. One hundred subjects (46%) developed new pain. The final
      tear type was associated with a greater risk of pain development, with the new
      pain developing in 28% of the controls, 46% of the shoulders with a partial
      thickness tear, and 50% of those with a full-thickness tear (p < 0.05). The
      presence of tear enlargement was associated with the onset of new pain (p <
      0.05). Progressive degenerative changes of the supraspinatus muscle were
      associated with tear enlargement, with supraspinatus muscle degeneration
      increasing in 4% of the shoulders with a stable tear compared with 30% of the
      shoulders with tear enlargement (p < 0.05). Nine percent of the shoulders with a
      stable tear showed increased infraspinatus muscle degeneration compared with 28%
      of those in which the tear had enlarged (p = 0.07). CONCLUSIONS: This study
      demonstrates the progressive nature of degenerative rotator cuff disease. The
      risk of tear enlargement and progression of muscle degeneration is greater for
      shoulders with a full-thickness tear, and tear enlargement is associated with a
      greater risk of pain development across all tear types. LEVEL OF EVIDENCE:
      Prognostic Level II. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 25609432
TI  - Endothelial CD74 mediates macrophage migration inhibitory factor protection in
      hyperoxic lung injury.
AB  - Exposure to hyperoxia results in acute lung injury. A pathogenic consequence of
      hyperoxia is endothelial injury. Macrophage migration inhibitory factor (MIF) has
      a cytoprotective effect on lung endothelial cells; however, the mechanism is
      uncertain. We postulate that the MIF receptor CD74 mediates this protective
      effect. Using adult wild-type (WT), MIF-deficient (Mif(-/-)), CD74-deficient
      (Cd74(-/-)) mice and MIF receptor inhibitor treated mice, we report that MIF
      deficiency or inhibition of MIF receptor binding results in increased sensitivity
      to hyperoxia. Mif(-/-) and Cd74(-/-) mice demonstrated decreased median survival
      following hyperoxia compared to WT mice. Mif(-/-) mice demonstrated an increase
      in bronchoalveolar protein (48%) and lactate dehydrogenase (LDH) (68%) following
      72 hours of hyperoxia. Similarly, treatment with MIF receptor antagonist resulted
      in a 59% and 91% increase in bronchoalveolar lavage protein and LDH,
      respectively. Inhibition of CD74 in primary murine lung endothelial cells (MLECs)
      abrogated the protective effect of MIF, including decreased hyperoxia-mediated
      AKT phosphorylation and a 20% reduction in the antiapoptotic effect of exogenous
      MIF. Treatment with MIF decreased hyperoxia-mediated H2AX phosphorylation in a
      CD74-dependent manner. These data suggest that therapeutic manipulation of the
      MIF-CD74 axis in lung endothelial cells may be a novel approach to protect
      against acute oxidative stress.

PMID- 25609435
TI  - Isolated gastrocnemius recession for achilles tendinopathy: strength and
      functional outcomes.
AB  - BACKGROUND: Gastrocnemius recession has emerged as a viable intervention for
      patients with recalcitrant foot and ankle disorders associated with isolated
      gastrocnemius contracture. The purpose of this case-control study was to
      investigate the effects of an isolated gastrocnemius recession on pain, patient
      reported function, and strength in patients with chronic Achilles tendinopathy
      and an isolated gastrocnemius contracture. METHODS: Thirteen patients with
      unilateral Achilles tendinopathy (mean age [and standard deviation], fifty-two +/
      7.7 years) who received a gastrocnemius recession and ten matched-control
      subjects participated. A visual analog scale was used to assess pain, and the
      Foot and Ankle Ability Measure was used to evaluate patient-reported function in
      activities of daily living and sports. Patients were asked about their
      satisfaction with the results of the gastrocnemius recession. Ankle plantar
      flexion peak torque was assessed at 60 degrees /sec and 120 degrees /sec.
      Appropriate t tests were used to assess limb symmetry and strength differences
      between the groups. RESULTS: The mean duration of follow-up was eighteen months
      (range, twelve to twenty-eight months). Gastrocnemius recession provided
      significant pain relief (mean preoperative visual analog scale score [and
      standard deviation], 6.8 +/- 1.8; mean follow-up visual analog scale score, 1.4
      +/- 2.7; p < 0.05). Foot and Ankle Ability Measure outcomes showed between-group
      differences in activities of daily living (Achilles tendinopathy group, 89.7;
      control group, 98.5; p = 0.05) and sports subscales (Achilles tendinopathy group,
      71.9; control group, 95.1; p = 0.05). The activities reported to be the most
      challenging included going up hills, climbing stairs, running, and jumping.
      Eleven of the thirteen patients in the Achilles tendon group were satisfied with
      treatment. Side-to-side strength comparisons showed no differences at 60 degrees
      /sec. Significant differences were observed at 120 degrees /sec (Achilles
      tendinopathy group, 21%; control group, 3%; p < 0.05); however, the involved limb
      reached a peak torque similar to that in the control limb. CONCLUSIONS: Isolated
      gastrocnemius recession provides significant and sustained pain relief for
      chronic Achilles tendinopathy. Good function can be expected for activities of
      daily living, but power and endurance activities were more problematic for the
      Achilles tendinopathy group. Isokinetic strength assessment may not effectively
      capture patient-reported functional deficits. LEVEL OF EVIDENCE: Therapeutic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25609436
TI  - Transverse fractures of the femoral shaft are a better predictor of nonaccidental
      trauma in young children than spiral fractures are.
AB  - BACKGROUND: Certain fracture configurations, especially spiral fractures, are
      often thought to be indicative of nonaccidental trauma in children. The purpose
      of this study was to determine whether femoral fracture morphology, as determined
      by an objective measurement (fracture ratio), was indicative of nonaccidental
      trauma in young children. METHODS: Consecutive patients who were three years of
      age or younger and had a closed, isolated femoral shaft fracture treated at an
      urban pediatric level-I trauma center between 2005 and 2013 were identified.
      Anteroposterior and lateral fracture ratios (fracture length/bone diameter) were
      calculated for each patient by a fellowship-trained pediatric orthopaedic surgeon
      who was blinded to the patient's clinical history. The presence or absence of a
      Child Protective Services referral as well as institutional Child Assessment
      Program evaluations were reviewed. Nonaccidental trauma was deemed to be present,
      absent, or indeterminate by Child Protective Services or an on-site Child
      Assessment Program team. To further evaluate and quantify the likelihood of
      nonaccidental trauma, the criteria of the Modified Maltreatment Classification
      System were used. RESULTS: Of 122 patients identified, ninety-five met the
      inclusion criteria for this study. Of these ninety-five, fifty-one (54%) had
      either a Child Protective Services or a Child Assessment Program consultation
      because of suspected nonaccidental trauma. Thirteen (25%) were found to have
      nonaccidental trauma as determined by Child Protective Services or the Child
      Assessment Program team and seven (14%) had indeterminate Child Protective
      Services or Child Assessment Program investigations. All thirteen patients with
      nonaccidental trauma, as well as the seven patients with an indeterminate Child
      Protective Services or Child Assessment Program investigation, had positive
      Modified Maltreatment Classification System scores for physical abuse. Patients
      who had nonaccidental trauma had significantly decreased mean anteroposterior
      fracture ratios compared with those who had confirmed accidental trauma (p <
      0.0001). CONCLUSIONS: The fracture ratio can be helpful to determine fracture
      morphology and can be used as part of the assessment of a child with suspected
      nonaccidental trauma. While not diagnostic, the presence of a transverse
      diaphyseal femoral fracture in a young child should raise the index of suspicion
      for nonaccidental trauma. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 25609437
TI  - Glenohumeral abduction contracture in children with unresolved neonatal brachial
      plexus palsy.
AB  - BACKGROUND: Following neonatal brachial plexus palsy, the Putti sign-obligatory
      tilt of the scapula with brachiothoracic adduction-suggests the presence of
      glenohumeral abduction contracture. In the present study, we utilized magnetic
      resonance imaging (MRI) to quantify this glenohumeral abduction contracture and
      evaluate its relationship to shoulder joint deformity, muscle atrophy, and
      function. METHODS: We retrospectively reviewed MRIs of the thorax and shoulders
      obtained before and after shoulder rebalancing surgery (internal rotation
      contracture release and external rotation tendon transfer) for twenty-eight
      children with unresolved neonatal brachial plexus palsy. Two raters measured the
      coronal positions of the scapula, thoracic spine, and humeral shaft bilaterally
      on coronal images, correcting trigonometrically for scapular protraction on axial
      images. Supraspinatus, deltoid, and latissimus dorsi muscle atrophy was assessed,
      blinded to other measures. Correlations between glenohumeral abduction
      contracture and glenoid version, humeral head subluxation, passive external
      rotation, and Mallet shoulder function before and after surgery were performed.
      RESULTS: MRI measurements were highly reliable between raters. Glenohumeral
      abduction contractures were present in twenty-five of twenty-eight patients,
      averaging 33 degrees  (range, 10 degrees  to 65 degrees ). Among those patients,
      abductor atrophy was present in twenty-three of twenty-five, with adductor
      atrophy in twelve of twenty-five. Preoperatively, greater abduction contracture
      severity correlated with greater Mallet global abduction and hand-to-neck
      function. Abduction contracture severity did not correlate preoperatively with
      axial measurements of glenohumeral dysplasia, but greater glenoid retroversion
      was associated with worse abduction contractures postoperatively. Surgery
      improved passive external rotation, active abduction, and hand-to-neck function,
      but did not change the abduction contracture. CONCLUSIONS: A majority of patients
      with persistent shoulder weakness following neonatal brachial plexus palsy have
      glenohumeral abduction deformities, with contractures as severe as 65 degrees .
      The abduction contracture occurs with abductor atrophy, with or without
      associated adductor atrophy. This contracture may improve global shoulder
      abduction by positioning the glenohumeral joint in abduction. Glenohumeral and
      scapulothoracic kinematics and muscle pathology must be further elucidated to
      advance an understanding of the etiology and the prevention and treatment of the
      complex shoulder deformity following neonatal brachial plexus palsy. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25609438
TI  - Two-stage surgical treatment of complex femoral deformities with severe coxa vara
      in polyostotic fibrous dysplasia.
AB  - BACKGROUND: In patients with polyostotic fibrous dysplasia with extensive femoral
      involvement, severe coxa vara may cause complex femoral deformities that are
      difficult to treat with a single-stage surgical procedure. We evaluated the
      results of treatment of such patients with a two-stage procedure. METHODS: Eleven
      patients with polyostotic fibrous dysplasia and severe coxa vara (including one
      who required bilateral treatment and one who required repeat treatment) were
      treated surgically at a mean age of fourteen years and four months. A two-stage
      surgical procedure was planned to correct the deformity. The first stage involved
      correction of the coxa vara and fixation with a hip plate. The second stage
      involved correction of a shepherd's crook deformity if present and definitive
      fixation with an interlocking cervicodiaphyseal nail. All patients were evaluated
      clinically and radiographically at a mean of four years and seven months after
      the second-stage procedure. RESULTS: The femoral neck-shaft angle averaged 83
      degrees  before surgery and was corrected to a mean of 130 degrees  after the
      first-stage procedure. In two patients, cutout of the hip screw-plate caused
      acute postoperative loss of correction (by 40 degrees  in one patient and 20
      degrees  in the other). After the second-stage procedure, the neck-shaft angle
      was either fully corrected or improved and the shepherd's crook deformity was
      fully corrected in all patients. At the time of the latest follow-up, the mean
      neck-shaft angle was 124 degrees , with a mean loss of correction of 5 degrees 
      relative to the angle measured at the end of the second-stage procedure. The mean
      estimated blood loss was 625 mL in the first stage and 979 mL in the second.
      CONCLUSIONS: The two-stage surgical procedure designed to treat patients with
      polyostotic fibrous dysplasia with complex femoral deformity and severe coxa vara
      restored a nearly normal femoral alignment that was maintained at a mean of four
      years and seven months of follow-up. The clinical benefits were pain relief in
      all of the patients and gait normalization or improvement in most. The estimated
      blood loss was substantial in both stages. LEVEL OF EVIDENCE: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25609439
TI  - Distal extension of the direct anterior approach to the hip poses risk to
      neurovascular structures: an anatomical study.
AB  - BACKGROUND: The anterior approach to the hip gained popularity for total hip
      arthroplasty in recent years. Distal extension of the anterior approach,
      sometimes needed intraoperatively, potentially endangers neurovascular structures
      to the quadriceps. The aim of this study was to determine the anatomical
      structures placed at risk by distal extension of the anterior approach to the
      hip. METHODS: Seventeen cadaveric hemipelves from twelve human specimens were
      dissected. The femoral nerve and its branches and the vessels arising from the
      lateral femoral circumflex artery were assessed in relation to the distal
      extension of the anterior approach. The damage caused by the introduction of a
      cerclage cable passer was also investigated. RESULTS: The area immediately distal
      to the intertrochanteric line is a common entry point for several nerve branches
      and is a useful distal landmark for surgeons to use to protect important
      neurovascular structures. The distal extension of the anterior approach
      compromises the nerve supply to the anterolateral portions of the quadriceps.
      Introduction of a cerclage cable passer through the anterior access also
      jeopardizes nerve branches to the vastus lateralis, lateral parts of the vastus
      intermedius, and branches of the lateral femoral circumflex artery. CONCLUSIONS:
      Distal extension of the direct anterior approach to the hip is challenging to
      accomplish without neurovascular injury to anterolateral parts of the quadriceps
      muscle group. In addition, important neurovascular structures are endangered with
      the introduction of a cable passer through the anterior approach. CLINICAL
      RELEVANCE: Distal extension of the direct anterior approach to the hip beyond the
      intertrochanteric line may compromise neurovascular structures supplying the
      quadriceps muscle.

PMID- 25609440
TI  - Sclerostin antibody treatment improves implant fixation in a model of severe
      osteoporosis.
AB  - BACKGROUND: The mechanical fixation of orthopaedic and dental implants is
      compromised by diminished bone volume, such as with osteoporosis. Systemic
      administration of sclerostin antibody (Scl-Ab) has been shown to enhance implant
      fixation in normal animals. In the present study, we tested whether Scl-Ab can
      improve implant fixation in established osteoporosis in a rat model. METHODS: We
      used an ovariectomized (ovx) rat model, in which we found a 78% decrease in
      trabecular bone volume at the time of implant surgery; sham-ovx, age-matched rats
      were used as controls. After placement of a titanium implant in the medullary
      cavity of the distal aspect of the femur, the rats were maintained for four,
      eight, or twelve weeks and treated biweekly with Scl-Ab or with the delivery
      vehicle alone. Outcomes were measured with use of microcomputed tomography,
      mechanical testing, and static and dynamic histomorphometry. RESULTS: Scl-Ab
      treatment doubled implant fixation strength in both the sham-ovx and ovx groups,
      although the enhancement was delayed in the ovx group. Scl-Ab treatment also
      enhanced bone-implant contact; increased peri-implant trabecular thickness and
      volume; and increased cortical thickness. These structural changes were
      associated with an approximately five to sevenfold increase in the bone-formation
      rate and a >50% depression in the eroded surface following Scl-Ab treatment.
      Trabecular bone thickness and bone-implant contact accounted for two-thirds of
      the variance in fixation strength. CONCLUSIONS: In this model of severe
      osteoporosis, Scl-Ab treatment enhanced implant fixation by stimulating bone
      formation and suppressing bone resorption, leading to enhanced bone-implant
      contact and improved trabecular bone volume and architecture. CLINICAL RELEVANCE:
      Systemic administration of anti-sclerostin antibodies might be a useful strategy
      in total joint replacement when bone mass is deficient.

PMID- 25609441
TI  - Adding insult to injury: discontinuous insurance following spine trauma.
AB  - BACKGROUND: Spine trauma patients may represent a group for whom insurance fails
      to provide protection from catastrophic medical expenses, resulting in the
      transfer of financial burden onto individual families and public payers. This
      study compares the rate of insurance discontinuation for patients who underwent
      surgery for traumatic spine injury with and without spinal cord injury with the
      rate for matched control subjects. METHODS: We used the MarketScan database to
      perform a retrospective cohort study of privately insured spine trauma patients
      who underwent surgery from 2006 to 2010. Kaplan-Meier survival analysis was used
      to assess the time to insurance discontinuation. Cox proportional-hazards
      regression was used to determine hazard ratios for insurance discontinuation
      among spine trauma patients compared with the matched control population.
      RESULTS: The median duration of existing insurance coverage was 20.2 months for
      those with traumatic spinal cord injury, 25.6 months for those with traumatic
      spine injury without spinal cord injury, and 48.0 months for the matched control
      cohort (log-rank p < 0.0001). After controlling for multiple covariates, the
      hazard ratios for discontinuation of insurance were 2.02 (95% CI [confidence
      interval], 1.83 to 2.23) and 2.78 (95% CI, 2.31 to 3.35) for the trauma patients
      without and with spinal cord injury, respectively, compared with matched
      controls. CONCLUSIONS: Rates of insurance discontinuation are significantly
      higher for trauma patients with severe spine injury compared with the uninjured
      population, indicating that patients with disabling injuries are at increased
      risk for loss of insurance coverage.

PMID- 25609442
TI  - Relationship of calcaneal and iliac apophyseal ossification to peak height
      velocity timing in children.
AB  - BACKGROUND: Ossification of the calcaneal apophysis has never been fully
      characterized. We examined the ossification sequence of the calcaneus in relation
      to ossification of the iliac apophysis and the timing of the peak height velocity
      (PHV). METHODS: Ninety-four healthy children (forty-nine girls and forty-five
      boys), from three to eighteen years old, were followed longitudinally through
      growth with annual serial radiographs and physical examinations. These were done
      at least annually from ten to fifteen years of age. The PHV was calculated using
      the height measurements of each child. We measured and compared calcaneal and
      iliac crest apophyseal ossification using foot and pelvic radiographs made on the
      same day. We correlated the PHV with the degree of calcaneal and iliac
      ossification. RESULTS: Ossification of the calcaneal apophysis occurred in an
      orderly fashion, with the ossification center first appearing a mean of 4.7 years
      (95% confidence interval [CI], 5.2 to 4.2 years) before the PHV. The apophysis
      spread across the plantar surface more quickly than the dorsal surface. The
      apophysis extended completely over the plantar surface a mean of 0.86 year (95%
      CI, 1.0 to 0.7 year) before the PHV. Fusion of the apophysis followed complete
      plantar extension over the next two years and was typically complete a mean of
      2.1 years (95% CI, 2.0 to 2.2 years) after the PHV. Fusion began in the middle of
      the apophysis and proceeded outward. Iliac apophyseal ossification did not appear
      prior to the PHV in any subject. CONCLUSIONS: The calcaneal apophysis ossifies in
      a consistent fashion characterized by six different stages. The calcaneal stages
      occur during narrow intervals in relation to the PHV, allowing the calcaneal
      system to be used for assessment of skeletal maturity. The PHV occurs prior to
      iliac ossification, whereas the calcaneal apophysis has four stages of
      ossification before and two stages after the PHV.

PMID- 25609443
TI  - Intermediate and long-term quality of life after total knee replacement: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Total knee replacement is a highly successful and frequently
      performed operation. Technical outcomes of surgery are excellent, with favorable
      early postoperative health-related quality of life. This study reviews
      intermediate and long-term quality of life after surgery. METHODS: A systematic
      review and meta-analysis of all studies published from January 2000 onward was
      performed to evaluate health-related quality of life after primary total knee
      replacement for osteoarthritis in patients with at least three years of follow
      up. Key outcomes were postoperative quality of life, function, and satisfaction
      compared with the preoperative status. Strict inclusion and exclusion criteria
      were applied. Quality appraisal and data tabulation were performed with use of
      predefined criteria. Data were synthesized by narrative review and random-effects
      meta-analysis utilizing standardized mean differences. Heterogeneity was assessed
      with the tau(2) and I(2) statistics. RESULTS: Nineteen studies were included in
      the review. Intermediate and long-term postoperative quality of life was superior
      to the preoperative level in qualitative and quantitative analyses. The pooled
      effect in combined WOMAC (Western Ontario and McMaster Universities
      Osteoarthritis Index) and KSS (Knee Society Score) outcomes was a marked
      improvement from baseline with respect to the total score (2.17; 95% CI
      [confidence interval], 1.13 to 3.22; p < 0.0001) and the pain (1.72; 95% CI, 0.97
      to 2.46; p < 0.00001) and function (1.26; 95% CI, 0.87 to 1.64; p < 0.00001)
      domains. Most patients were satisfied with the surgery and derived substantial
      benefits for daily functional activities. Tau(2) (0.20 to 1.10) and I(2) (90% to
      98%) values implied significant clinical and statistical heterogeneity.
      CONCLUSIONS: Total knee replacement confers significant intermediate and long
      term benefits with respect to both disease-specific and generic health-related
      quality of life, especially pain and function, leading to positive patient
      satisfaction. Recommendations for necessary future studies are provided. LEVEL OF
      EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25609444
TI  - What's new in adult reconstructive knee surgery.

PMID- 25609445
TI  - Insult to Injury-Indeed: Commentary on an article by Zachary J. Kastenberg, MD,
      et al.: "Adding Insult to Injury: Discontinuous Insurance Following Spine
      Trauma".

PMID- 25609446
TI  - Current concepts in the biopsy of musculoskeletal tumors: AAOS exhibit selection.
AB  - BACKGROUND: A musculoskeletal tumor biopsy can involve fine needle aspiration,
      core needle biopsy, or incisional biopsy. Controversy regarding the diagnostic
      yield of these biopsy techniques continues. The purpose of this article is to
      summarize the current concepts in the biopsy of musculoskeletal tumors. METHODS:
      We performed a literature review of clinical articles reporting on the biopsy of
      bone and soft-tissue primary tumors. Clinical articles were excluded on the basis
      on abstract content if they represented case reports, review or opinion articles,
      or technique descriptions. Eighteen of the thirty-nine articles that remained
      were excluded because the results did not indicate the diagnostic accuracy of the
      various biopsy techniques. Thus, twenty-one articles with diagnostic data on the
      biopsy of bone and soft-tissue tumors were included in this review. RESULTS: Core
      needle biopsy appeared to be more accurate than fine needle aspiration, and
      incisional biopsy appeared to be more accurate than both of these techniques, but
      the differences did not reach significance. Incisional biopsy was more expensive
      than the percutaneous biopsy methods. In deep musculoskeletal tumors,
      incorporation of ultrasonography or computed tomography for guidance is easy and
      safe and can be useful for increasing the accuracy of the biopsy. Advantages of a
      percutaneous technique compared with an incisional one are the low risk of
      contamination and the minimally invasive nature. Certain anatomic locations and
      histologic types were associated with diagnostic difficulty. Vertebral tumors had
      the lowest diagnostic accuracy regardless of the biopsy technique. Myxoid,
      infection, and round cell histologies were associated with the lowest diagnostic
      accuracy. CONCLUSIONS: The current literature has not clarified the optimal
      biopsy technique for the diagnosis of bone and soft-tissue tumors. However, core
      needle biopsy is usually preferable to incisional biopsy because of the low risk
      of contamination and the low cost. In addition, the use of imaging guidance
      increases the diagnostic accuracy of musculoskeletal biopsies and reduces the
      risk of complications. If the result of a percutaneous biopsy is nondiagnostic, a
      small incisional biopsy should be performed. LEVEL OF EVIDENCE: Diagnostic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25609447
TI  - The validity of level of evidence ratings of articles submitted to JBJS.
AB  - BACKGROUND: In 2003, The Journal of Bone & Joint Surgery (American Volume)
      implemented a requirement for submitted clinical research articles to include a
      level of evidence rating. The aim of this study was to analyze the agreement
      between authors and JBJS regarding the level of evidence rating of accepted
      clinical articles. METHODS: A random sample of 353 clinical research articles
      accepted by JBJS from 2010 to 2012 was analyzed; 188 had a level of evidence
      rating provided by the author. Articles were grouped by study type and
      subspecialty. An unweighted kappa value was calculated to measure agreement
      between the authors and the JBJS editor, whose decision was used as the gold
      standard. In a secondary analysis, the articles in each subspecialty were
      categorized according to the year of submission to evaluate temporal trends.
      RESULTS: Of the 353 articles, 69.4% (245) were classified by JBJS as representing
      a therapeutic study, 17.6% (sixty-two) were classified as representing Level-I
      evidence, and 25.2% (eighty-nine) dealt with arthroplasty. Agreement between the
      author and the JBJS editor was 0.79 (95% confidence interval [CI], 0.71 to 0.89;
      p < 0.001) for the study type, 0.62 (95% CI, 0.53 to 0.70; p < 0.001) for the
      level of evidence, and 0.65 (95% CI, 0.58 to 0.73; p < 0.001) for the full level
      of evidence rating (study type and level of evidence). CONCLUSIONS: Level of
      evidence ratings suggested by authors from 2010 to 2012 had moderate to
      substantial agreement with the ratings assigned by the JBJS editor. This suggests
      that the level of evidence rating system is being properly understood by authors
      of articles published in JBJS. However, the low frequency of reporting suggests
      that JBJS needs to strictly enforce requirements for submission of a level of
      evidence rating at the time of manuscript submission.

PMID- 25609448
TI  - Gastrocnemius recession: a Panacea for What Ails the foot and ankle: commentary
      on an article by Deborah A. Nawoczenski, PT, PhD, et al.: "isolated gastrocnemius
      recession for achilles tendinopathy: strength and functional outcomes".

PMID- 25609450
TI  - The paradox of artificial sweeteners in managing obesity.
AB  - The role of artificial sweeteners in the management of obesity is controversial.
      Observational data have suggested that nonnutritive sweeteners (NNSs) may promote
      weight gain through poorly understood mechanisms of cravings, reward phenomenon,
      and addictive behavior via opioid receptors. Interventional studies suggest the
      opposite that substitution of NNS for sugar-sweetened beverages (SSBs) results in
      reduced caloric intake and modest degrees of weight loss. Whether the use of NNS
      provides benefit toward weight reduction in the individual patient may depend on
      the characteristics of their baseline diet, associated changes, or dietary
      compensation involved with ingestion of NNS, and the degree of compliance with a
      more complete weight loss program. 

PMID- 25609449
TI  - Longitudinal and cross sectional assessments of health utility in adults with
      HIV/AIDS: a systematic review and meta-analysis.
AB  - BACKGROUND: Utility estimates are important health outcomes for economic
      evaluation of care and treatment interventions for patients with HIV/AIDS. We
      conducted a systematic review and meta-analysis of utility measurements to
      examine the performance of preference-based instruments, estimate health utility
      of patients with HIV/AIDS by disease stages, and investigate changes in their
      health utility over the course of antiretroviral treatment. METHODS: We searched
      PubMed/Medline, Cochrane Database of Systematic Review, NHS Economic Evaluation
      Database and Web of Science for English-language peer-reviewed papers published
      during 2000-2013. We selected 49 studies that used 3 direct and 6 indirect
      preference based instruments to make a total of 218 utility measurements. Random
      effect models with robust estimation of standard errors and multivariate
      fractional polynomial regression were used to obtain the pooled estimates of
      utility and model their trends. RESULTS: Reliability of direct-preference
      measures tended to be lower than other types of measures. Utility elicited by two
      of the indirect preference measures - SF-6D (0.171) and EQ-5D (0.114), and that
      of Time-Trade off (TTO) (0.151) was significantly different than utility elicited
      by Standard Gamble (SG). Compared to asymptomatic HIV patients, symptomatic and
      AIDS patients reported a decrement of 0.025 (p = 0.40) and 0.176 (p = 0.001) in
      utility scores, adjusting for method of assessment. In longitudinal studies, the
      pooled health utility of HIV/AIDS patients significantly decreased in the first 3
      months of treatment, and rapidly increased afterwards. Magnitude of change varied
      depending on the method of assessment and length of antiretroviral treatment.
      CONCLUSION: The study provides an accumulation of evidence on measurement
      properties of health utility estimates that can help inform the selection of
      instruments for future studies. The pooled estimates of health utilities and
      their trends are useful in economic evaluation and policy modelling of HIV/AIDS
      treatment strategies.

PMID- 25609451
TI  - A phase II trial of concurrent 3D-CRT/IMRT and oxaliplatin, 5-fluorouracil and
      leucovorin (FOLFOX) in gastric cancer patients with R0 gastrectomy and D2 lymph
      node dissection.
AB  - BACKGROUND: To evaluate the safety and efficacy of a concurrent three-dimensional
      conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) plus
      oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) regimen in completely
      resected gastric cancer patients with D2 lymph node dissection. MATERIALS AND
      METHODS: Patients with stage IB-IIIC gastric cancer (per the AJCC, 7th edition)
      who had undergone R0 and D2 gastrectomy were recruited. Two cycles of FOLFOX with
      concurrent 3D-CRT or IMRT (50.4 Gy/28f) were administered. One and an additional
      five cycles of FOLFOX were delivered before and after concurrent
      chemoradiotherapy, respectively. Primary endpoints were relapse-free survival
      (RFS) and overall survival (OS), with adverse events as secondary endpoints.
      RESULTS: From 2008 to 2011, 110 patients were evaluable. The 1-, 2- and 3-year
      RFS and OS were 86.2, 72.2, 67.8 and 94.7, 87.2, 77.6%, respectively. On
      multivariate analysis, stage (<= IIIA vs. >IIIA) was a statistically significant
      factor affecting both RFS and OS. Additionally, the T-category (<= T4a vs. = T4b)
      was a statistically significant factor affecting only the RFS. The most commonly
      observed grade 3 or 4 adverse events were nausea and vomiting, decreased
      appetite, leukopenia/neutropenia and fatigue, each of which occurred in 14.5,
      11.8, 9.1 and 6.4% patients, respectively. CONCLUSIONS: Adjuvant 3D-CRT/IMRT to a
      dose of 50.4 Gy/28f with concurrent FOLFOX is safe and effective in patients
      following radical gastrectomy with D2 lymph node dissection.

PMID- 25609452
TI  - Helicobacter pylori eradication cannot reduce the risk of gastric cancer in
      patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis.
AB  - BACKGROUND: The effect of Helicobacter pylori (H. pylori) eradication on gastric
      cancer (GC) prevention is controversial. Intestinal metaplasia (IM) seems to be a
      "point of no return" in the precancerous cascade. We performed a meta-analysis of
      randomized controlled trials (RCTs) to illustrate this issue. MATERIALS AND
      METHODS: The MEDLINE, EMBASE, Cochrane Library were searched for relevant RCTs
      that were published in any language up to March 2014. By dividing participants
      into subgroups based on their baseline diagnoses as group <IM (normal, non
      atrophic gastritis, atrophic gastritis) and group >= IM(intestinal metaplasia,
      dysplasia), the relative risk (RR) of GC in each study compared treatment group
      with control group were pooled using Mantel-Haenszel fixed-effect model and
      publication bias analyses were performed. RESULTS: Ten studies from eight RCTs
      were included in this analysis, for a total of 7,955 participants. H. pylori
      treatment compared with control significantly reduced the risk of GC, with a
      pooled RR of 0.64 (95% CI, 0.48-0.85). Subgroup analysis for patients with non
      atrophic gastritis, atrophic gastritis (<IM) yielded a similar results (RR =
      0.25, 95% CI, 0.08-0.81). But this difference was not observed in patients with
      intestinal metaplasia, dysplasia (>= IM) (RR = 0.88; 95% CI, 0.59-1.31).
      CONCLUSIONS: Our results suggested that patients with Intestinal metaplasia or
      dysplasia could not benefit from the H. pylori treatment on the risk of GC.

PMID- 25609454
TI  - Chronological analysis of gross and histological lesions induced by field strains
      of fowl adenovirus serotypes 1, 8b and 11 in one-day-old chickens.
AB  - Fowl adenoviruses (FAdVs) cause diseases in domestic chickens, including
      inclusion body hepatitis (IBH), with immunosuppression believed to play a role in
      their pathogenesis. To gain a better understanding of the pathogenesis and
      chronology of disease caused by FAdVs, the gross pathology, histopathology and
      dissemination of virus were examined at several different time points, after
      inoculation of one-day-old specific pathogen-free chickens with FAdV-1, FAdV-8b
      or FAdV-11 via the ocular route. FAdV-8b had a slightly greater virulence than
      FAdV-11, but both were primary pathogens. The presence and severity of hepatic
      lesions were used to define the three stages of the disease: incubation (1-3 days
      post-inoculation, PI), degeneration (4-7 days PI) and convalescence (14 days PI).
      Both viruses were detected in the liver, kidney, bursa, thymus and gizzard of
      most birds during the degenerative stage, and persisted in the gizzard into
      convalescence. The FAdV-1 isolate was found to be apathogenic, but virus was
      detected in the bursa and/or gizzard of several birds between 2 and 7 days PI.
      This is the first study examining the chronology of gross and microscopic lesions
      of pathogenic and apathogenic FAdVs in association with viral presence in
      multiple tissues. It was concluded that both FAdV-8b and FAdV-11 are primary
      pathogens, and that these strains may play a role in immunosuppression. 

PMID- 25609453
TI  - Methylation status of long interspersed element-1 in advanced gastric cancer and
      its prognostic implication.
AB  - BACKGROUNDS: Reportedly, the pyrosequencing methylation assay can produce
      inconsistent results between paired snap-frozen and formalin-fixed paraffin
      embedded archival tissue samples. In this study, we assayed the methylation
      levels at four individual CpG sites of L1 using pyrosequencing and found that the
      methylation levels at individual CpG sites were different but were closely
      correlated between paired snap-frozen and formalin-fixed paraffin-embedded tissue
      samples. We aimed to determine whether low methylation status of L1 is associated
      with gastric cancer patient prognosis. METHODS: We analyzed 434 formalin-fixed
      paraffin-embedded tissue samples of advanced gastric cancer for their methylation
      status at four CpG sites of L1 [nucleotide positions 328, 321, 318, and 306 of
      X58075 (Genbank)] using pyrosequencing, and correlated the L1 methylation level
      with clinicopathological features. RESULTS: Older age at onset, males, tumor
      location at antrum or lower body, intestinal type, and lymphatic or venous
      invasion were associated with a low average methylation level of L1 at the two
      CpG sites 1 and 4 combined. The average methylation level of L1 at CpG sites 1
      and 4 combined was significantly lower in microsatellite-stable and EBV-negative
      gastric cancers than in EBV-positive or microsatellite-unstable gastric cancers.
      Low methylation status of L1 was independently correlated with shorter overall
      survival and disease-free survival time. CONCLUSION: Our findings indicate that
      the discrepancy in the methylation level of L1 between fresh tissue and formalin
      fixed paraffin-embedded tissue samples depends on the CpG sites considered, and
      that the methylation status of L1 at CpG sites 1 and 4 combined could be utilized
      as a prognostic parameter for advanced gastric cancers.

PMID- 25609455
TI  - Fractional transfer of a free unpaired electron to overcome energy barriers in
      the formation of Fe(4+) from Fe(3+) during the core contraction of macrocycles:
      implication for heme distortion.
AB  - The free unpaired electron in Fe(3+) ions cannot be directly removed, and needs a
      transfer pathway with at least four steps to overcome the high energy barriers to
      form Fe(4+) ions. Fine changes in the electronic structure of Fe(3+) ions on spin
      conversion were identified through a deeper analysis of the diffraction, spectral
      and electrochemical data for six non-planar iron porphyrins. Fe(3+) ions can form
      four d electron tautomers as the compression of the central ion is increased.
      This indicates that the Fe(3+) ion undergoes a multistep electron transfer where
      the total energy gap of electron transfer is split into several smaller gaps to
      form high-valent Fe(4+) ions. We find that the interchange of these four electron
      tautomers is clearly related to the core size of the macrocycle in the current
      series. The large energy barrier to produce iron(iv) complexes is overcome
      through a gradient effect of multiple energy levels. In addition, a possible
      porphyrin Fe(3+) radical may be formed from its stable isoelectronic form,
      porphyrin Fe(3+), under strong core contraction. These results indicate the
      important role of heme distortion in its catalytic oxidation functions. 

PMID- 25609456
TI  - Ultrasound-guided high intensity focused ultrasound for the treatment of
      gynaecological diseases: A review of safety and efficacy.
AB  - As a non-surgical treatment, high intensity focused ultrasound (HIFU) has
      received increasing interest for the treatment of gynaecological diseases over
      the last 10 years. Many studies have shown that HIFU is safe and effective in
      treating patients with uterine fibroids, adenomyosis, cervicitis or vulvar
      diseases. Both magnetic resonance imaging-guided HIFU (MRgHIFU) and ultrasound
      guided HIFU (USgHIFU) can offer gynaecologists non-invasive techniques to treat
      patients with uterine benign diseases. Focused ultrasound therapy can also be
      used effectively to treat cervicitis and vulvar diseases. As gynaecologists gain
      more experience with this technology, the rate of severe adverse effects has been
      lowered with the development of this non-invasive technique. In this paper we
      review the literature available regarding the utilisation of magnetic resonance
      imaging-guided focused ultrasound/MRgHIFU or USgHIFU and new findings from our
      group in the treatment of gynaecological diseases: uterine fibroids, adenomyosis,
      cervicitis, vulvar diseases, caesarean scar pregnancies, and abdominal wall
      endometriosis. 

PMID- 25609457
TI  - JALA: advancing translational laboratory science and technology for 20 years!

PMID- 25609458
TI  - Congratulations to The 2015 JALA Ten!

PMID- 25609460
TI  - Cancer imaging: quo vadis?

PMID- 25609462
TI  - Determination of the quantized topological magneto-electric effect in topological
      insulators from Rayleigh scattering.
AB  - Topological insulators (TIs) exhibit many exotic properties. In particular, a
      topological magneto-electric (TME) effect, quantized in units of the fine
      structure constant, exists in TIs. Here, we theoretically study the scattering
      properties of electromagnetic waves by TI circular cylinders particularly in the
      Rayleigh scattering limit. Compared with ordinary dielectric cylinders, the
      scattering by TI cylinders shows many unusual features due to the TME effect. Two
      proposals are suggested to determine the TME effect of TIs simply by measuring
      the electric-field components of scattered waves in the far field at one or two
      scattering angles. Our results could also offer a way to measure the fine
      structure constant. 

PMID- 25609463
TI  - The disruptive influence of syphilis cures within specialist venereal systems:
      implications for HIV cure preparedness.

PMID- 25609461
TI  - Cetaceans evolution: insights from the genome sequences of common minke whales.
AB  - BACKGROUND: Whales have captivated the human imagination for millennia. These
      incredible cetaceans are the only mammals that have adapted to life in the open
      oceans and have been a source of human food, fuel and tools around the globe. The
      transition from land to water has led to various aquatic specializations related
      to hairless skin and ability to regulate their body temperature in cold water.
      RESULTS: We present four common minke whale (Balaenoptera acutorostrata) genomes
      with depth of *13 ~ *17 coverage and perform resequencing technology without a
      reference sequence. Our results indicated the time to the most recent common
      ancestors of common minke whales to be about 2.3574 (95% HPD, 1.1521 - 3.9212)
      million years ago. Further, we found that genes associated with epilation and
      tooth-development showed signatures of positive selection, supporting the
      morphological uniqueness of whales. CONCLUSIONS: This whole-genome sequencing
      offers a chance to better understand the evolutionary journey of one of the
      largest mammals on earth.

PMID- 25609464
TI  - The BASHH HIV Special Interest Group (SIG).

PMID- 25609465
TI  - Denis Lambert Sugrue.

PMID- 25609466
TI  - After Venus, mercury: syphilis treatment in the UK before Salvarsan.

PMID- 25609467
TI  - Magic bullet: Paul Ehrlich, Salvarsan and the birth of venereology.

PMID- 25609468
TI  - The magic bullet hits many targets: Salvarsan's impact on UK health systems, 1909
      1943.

PMID- 25609469
TI  - A cure at last? Penicillin's unintended consequences on syphilis control, 1944
      1964.

PMID- 25609470
TI  - The impact of penicillin on sexual healthcare delivery systems in mid-20th
      century Britain.

PMID- 25609471
TI  - Syphilis cure posters.

PMID- 25609473
TI  - Correction.

PMID- 25609474
TI  - Correction.

PMID- 25609477
TI  - Obama promises to defend health law and promote "precision medicine".

PMID- 25609476
TI  - Potent effects of dioscin against obesity in mice.
AB  - The mechanisms of the natural product dioscin against non-alcoholic fatty liver
      disease (NAFLD) are unclear. Thus, the purpose of the present study was to
      further confirm its effects of prevention and then to elucidate the potential
      mechanisms underlying its activity in mice. High-fat diet (HFD)-induced C57BL/6J
      mice and ob/ob mice were used as the experimental models. Serum and hepatic
      biochemical parameters were determined, and the mRNA and protein expression
      levels were detected. The results indicated that dioscin alleviated body weight
      and liver lipid accumulation symptoms, increased oxygen consumption and energy
      expenditure, and improved the levels of serum and hepatic biochemical parameters.
      Further investigations revealed that dioscin significantly attenuated oxidative
      damage, suppressed inflammation, inhibited triglyceride and cholesterol
      synthesis, promoted fatty acid beta-oxidation, down-regulated MAPK
      phosphorylation levels, and induced autophagy to alleviate fatty liver
      conditions. Dioscin prevents diet induced obesity and NAFLD by increasing energy
      expenditure. This agent should be developed as a new candidate for obesity and
      NAFLD prevention. 

PMID- 25609478
TI  - Nonthermal sensory input and altered human thermoregulation: effects of visual
      information depicting hot or cold environments.
AB  - A recent study showed that thermoregulatory-like cardiovascular responses can be
      invoked simply by exposure to visual information, even though the thermal
      environments are neutral and unchanged. However, it was not clear how such
      responses affect actual human body temperature regulation. We investigated
      whether such visually invoked physiological responses can substantively affect
      human core body temperature in a thermally challenging cold environment.
      Participants comprised 13 graduate or undergraduate students viewing different
      video images containing hot, cold, or no scenery, while room temperature was
      gradually lowered from 28 to 16  degrees C over 80 min. Rectal temperature, mean
      skin temperature, core to skin temperature gradient, and oxygen consumption were
      measured during the experiment. Rectal temperature was significantly lower when
      hot video images were presented compared to when control video images were
      presented. Oxygen consumption was comparable among all video images, but core to
      skin temperature gradient was significantly lower when hot video images were
      presented. This result suggests that visual information, even in the absence of
      thermal energy, can affect human thermodynamics and core body temperature.

PMID- 25609475
TI  - The role of diffusion and perfusion weighted imaging in the differential
      diagnosis of cerebral tumors: a review and future perspectives.
AB  - The role of conventional Magnetic Resonance Imaging (MRI) in the detection of
      cerebral tumors has been well established. However its excellent soft tissue
      visualization and variety of imaging sequences are in many cases non-specific for
      the assessment of brain tumor grading. Hence, advanced MRI techniques, like
      Diffusion-Weighted Imaging (DWI), Diffusion Tensor Imaging (DTI) and Dynamic
      Susceptibility Contrast Imaging (DSCI), which are based on different contrast
      principles, have been used in the clinical routine to improve diagnostic
      accuracy. The variety of quantitative information derived from these techniques
      provides significant structural and functional information in a cellular level,
      highlighting aspects of the underlying brain pathophysiology. The present work,
      reviews physical principles and recent results obtained using DWI/DTI and DSCI,
      in tumor characterization and grading of the most common cerebral neoplasms, and
      discusses how the available MR quantitative data can be utilized through advanced
      methods of analysis, in order to optimize clinical decision making. 

PMID- 25609479
TI  - The attitudes of psychiatric hospital staff toward hospitalization and treatment
      of patients with borderline personality disorder.
AB  - BACKGROUND: Negative attitudes towards patients with borderline personality
      disorder (BPD) may affect their treatment. We aimed to identify attitudes toward
      patients with BPD. METHODS: Clinicians in four psychiatric hospitals in Israel (n
      = 710; psychiatrists, psychologists, social workers and nurses) were approached
      and completed questionnaires on attitudes toward these patients. RESULTS: Nurses
      and psychiatrists reported encountering a higher number of patients with BPD
      during the last month, and exhibited more negative attitudes and less empathy
      toward these patients than the other two professions. The whole sample evaluated
      the decision to hospitalize such a patient as less justified than the decision to
      hospitalize a patient with Major Depressive Disorder. Negative attitudes were
      positively correlated with caring for greater numbers of patients with BPD in the
      past month and in the past 12 months. Nurses expressed the highest interest in
      studying short-term methods for treating patients with BPD and a lower percentage
      of psychiatrists expressed an interest in improving their professional skills in
      treating these patients. CONCLUSIONS: The findings show that nurses and
      psychiatrists differ from the other professions in their experience and attitudes
      toward patients with BPD. We conclude that nurses and psychiatrists may be the
      target of future studies on their attitudes toward provocative behavioral
      patterns (e.g., suicide attempts) characterizing these patients. We also
      recommend implementing workshops for improving staff attitudes toward patients
      with BPD.

PMID- 25609480
TI  - [Rare cancers and new radiotherapy techniques].
AB  - Rare cancers represent about a quarter of all cancers diagnosed in Europe, and
      their incidence is increasing. Meanwhile, scientific advances provide techniques,
      which become more and more sophisticated in the domain of radiotherapy. Treatment
      options for radiotherapy rare cancers are increasing, but are not yet evaluated.
      The question of the appropriateness of treatment by modern radiotherapy
      techniques in rare cancers remains. There are a lot of cases reported in the
      literature for treating rare cancers by modern technology. These techniques are
      often used when anatomical and dosimetric constraints do not achieve optimal
      treatment by surgery or standard radiotherapy. In contrast, standard radiotherapy
      techniques also provide good results in terms of overall survival and tolerance.
      They are also less expensive and less complex in terms of dosimetry. The
      establishment of specialized centers in rare cancers seems essential to evaluate
      the appropriateness of the use of modern techniques in these cases. Currently,
      data from the literature does not provide an answer to this question. 

PMID- 25609481
TI  - [Mecanisms of pharmacokinetic interactions involving oral anticancer agents].
AB  - Oral anticancer agents and particularly kinase inhibitors are subject to
      pharmacokinetic drug interactions in relation to absorption and elimination
      phases. Interacting factors are food, fruit juices, cigarette smoke, acid
      reducing agents and inducers/inhibitors. Some anticancer agents are inducers
      and/or inhibitors and can also perpetrate drug interactions. This review
      emphasizes the mechanisms of pharmacokinetic drug interactions involving oral
      anticancer agents. 

PMID- 25609482
TI  - [Update on genetic predisposition to prostate cancer].
AB  - Genetic predisposition to prostate cancer rarely corresponds to a high penetrance
      Mendelian pattern of inheritance. These hereditary forms are specific entities
      for which mutations in the BRCA2 gene, the HOXB13 gene (variant G84E) or, to a
      lesser extent BRCA1 gene, must be researched. In contrast, the genetic component
      of the majority of prostate cancer is polygenic, involving an unfavorable
      combination of common genetic variants, resulting from a mixture of the genetic
      inheritance of the father and the mother. One hundred of these genetic
      susceptibility variants have now been identified and validated. The main
      phenotypic trait associated with hereditary predisposition is the younger age at
      onset, which warrants special monitoring in order to stay in the window of
      curability at diagnosis. The psychological impact of a family history of prostate
      cancer or breast cancer favors the establishment of a dedicated monitoring and
      procedures for early diagnosis. 

PMID- 25609483
TI  - [Aging and cancer care in France: hospitalization requirement in 2012].
AB  - INTRODUCTION: French national cancer plans were rolled out oncogeriatric
      coordination units in France in particular to enable all elderly people with
      cancer in each region to benefit from a specific care management. METHODS: The
      national hospital discharge database was analyzed in order to analyze
      hospitalizations related to cancer care in >=75 years patients for year 2012.
      RESULTS: A total of 358,721 patients with 1,492,935 hospitalizations were
      recorded, respectively with chemotherapy (32.4%), radiotherapy (23.0%), surgery
      (10.6%), palliative care (3.9%), or other care (30.9%). Hospital activity was
      distributed in hospitals (36.3%), clinics (23.4%), academic hospitals (20.9%),
      cancer centers (11.8%). Their respective share varied according to care. Total
      activity volume and number of health care facilities involved were highly
      variable in the different regions. CONCLUSION: These data would permit
      development of a national oncogeriatric policy through the action of regional
      oncogeriatric coordination units. These units should prioritize training actions
      and good practice guidelines dissemination in health care institutions with a
      high activity volume in this domain.

PMID- 25609484
TI  - [Communication in the context of phase I clinical trials in oncology:
      implementation and evaluation of training programs].
AB  - Communication training programs in oncology have demonstrated some efficacy to
      improve doctors' communication skills. The goal of our study was to evaluate the
      impact of such training in the particular context of phase I clinical trials.
      Self-satisfaction and self-efficacy scales evaluating doctor-patient
      communication was completed by 6 medical oncologists (3 juniors and 3 seniors)
      before and after their communication training for a total of sixty visits. Two
      types of visit have been distinguished: the visits between the oncologist and the
      patient alone (a dual situation) and those with a third party (a trilateral
      situation). For all the doctors in dual and trialateral situations, self-efficacy
      scores improved significantly after training. This improvement was more
      pronounced for juniors oncologists in trilateral situations. Before training,
      satisfactory scores were worst in duel versus trilateral situations (P=0.01).
      This was particularly pronounced for junior compared to senior doctors (P=0.035).
      After training, in trilateral situations, the satisfaction scores of junior
      doctors matched that of the senior doctors. The communication training programs
      appear to benefit junior oncologists to a greater extent in trilateral
      situations.

PMID- 25609485
TI  - Functional TP53 mutations have no impact on response to cytotoxic agents in
      metastatic colon cancer.
AB  - BACKGROUND: Survival of metastatic colon cancer (mCC) patients has considerably
      improved with optimization of new drugs regimen. Inactivation of TP53 pathway by
      TP53 mutations is observed in nearly half of colorectal tumors. The impact of
      such mutations has been poorly studied in the metastatic setting. METHODS: The
      files of 254 mCC treated in a single institution at Saint-Louis hospital between
      January 1999 and April 2011 were retrospectively reviewed. Tissue samples for
      analysis of TP53 mutations were available for 68 patients, performed using FASAY.
      The prognostic value of TP53 status was evaluated by comparing progression free
      survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild
      type patients. RESULTS: PFS was 6.9 months and OS 21.7 months in the whole
      population. There was no statistical difference in TP53-mutated and wild type
      groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53
      1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only
      BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and
      OS, and CEA level for OS. CONCLUSIONS: Routine determination of TP53 mutations,
      even with a highly sensitive method, cannot be recommended to predict
      chemotherapy response in mCC.

PMID- 25609487
TI  - [Nanoparticles and radiation therapy].
AB  - BACKGROUND: Nanoparticles have emerged in oncology as new therapeutic agents of
      distinct biochemical and physical properties, and pharmacokinetics. Current
      rationale and clinical applications in combination with radiation therapy were
      analyzed. MATERIAL AND METHODS: A review of the literature was conducted on
      nanoparticles as radiosensitizers, with a focus on metallic nanoparticles and
      radiosensitization mechanisms. RESULTS: Nanoparticles are mainly used as vectors
      for drugs or to potentiate dose deposit selectively in irradiated tissues.
      Preclinical data suggest a predominating effect in the kilovoltage range through
      a photoelectric effect and a potential in the megavoltage range under a
      combination of physical and biochemical (diameter, concentration, site of
      infusion etc) conditions. Several clinical trials are ongoing with
      metallic/crystalline nanoparticles. CONCLUSION: Nanoparticles have shown a
      potential for better therapeutic index with radiation therapy, which is being
      increasingly investigated clinically.

PMID- 25609486
TI  - [Major advances in oncology in 2014: the editorial board of the Bulletin du
      Cancer point of view].
AB  - Results of many clinical trials are presented each year during the American
      Society of Clinical Oncology meeting, ESMO meeting and other international major
      meetings. This article is proposed by the editorial board of the Bulletin du
      Cancer as a synthesis of new important results in clinical trials concerning
      cancer patients treated for hematology cancer or solid tumors. The goal of this
      review is to highlight the main results that may have an immediate impact on our
      clinical practices for physicians and patients. 

PMID- 25609489
TI  - Intratumoral heterogeneity and consequences for targeted therapies.
AB  - According to the clonal model and Darwinian evolution, cancer cell evolves
      through new mutations helping it to proliferate, migrate, invade and metastasize.
      Recent genetic studies have clearly shown that tumors, when diagnosed, consist of
      a large number of mutations distributed in different cells. This heterogeneity
      translates in substantial genetic plasticity enabling cancer cells to adapt to
      any hostile environment. As targeted therapy focuses only on one pathway or
      protein, there will always be a cell with the "right" genetic background to
      survive the treatment and cause tumor relapse. Because today's targeted therapies
      never took tumor heterogeneity into account, nearly all novel drugs fail to
      provide patients with a considerable improvement of the survival. However,
      emerging proteomic studies guided by the idea that Darwinian selection is
      governed by the phenotype and not genotype, show that heterogeneity at the
      protein level is much less complex, then it could be expected from genetic
      studies. This information together with the recent trend to switch from
      functional to cytotoxic targeting may offer an entirely new strategy to
      efficiently combat cancer. 

PMID- 25609488
TI  - [The role of the expansion cohort in phase I trials in oncology: guidelines of
      the phase I HUB].
AB  - At the end of the dose escalation step of phase I trials in oncology, it is
      increasingly frequent to include patients in expansion cohorts. However, the
      objective of the expansion cohorts, the number of patients included and their
      justification are insufficiently explained in the protocols. These cohorts are
      sometimes of considerable size. The aim of this article is to outline the
      methodology of expansion cohorts in order to provide recommendations for their
      planning in practice. This work has been undertaken in collaboration with the
      statisticians of the early phase investigation centers (CLIP(2)), supported by
      INCA. First, we have outlined the recent articles published on the expansion
      cohorts in phase I. We then proposed recommendations, in terms of objectives and
      number of patients to be included, to guide investigators and facilitate the use
      of these expansion cohorts in practice. Manji et al. have identified 149 phase I
      clinical trials using expansion cohorts in oncology with a review of the
      literature between 2006 and 2011 (Manji et al., 2013). Objectives of the
      expansion cohort were reported in 111 trials (74%). In these trials, safety was
      the most reported objective (80% of trials), followed by efficacy (45%).
      According to this review, the number of patients included in these cohorts was
      insufficiently justified. This result was confirmed by the study of literature
      that we conducted over the period 2011-2014. We propose to define the number of
      patients to be included in expansion cohorts in terms of (1) their objectives,
      (2) the statistical criteria and (3) the clinical context of the trial. The
      toxicity study remains the primary objective to evaluate in the expansion phase.
      In some contexts, the activity study is considered as co-primary objective,
      either for identifying preliminary signs of activity in studies like screening,
      or for studying the activity when the target population is known. This study is
      then considered as phase I/II, and experience plans of phase II can be adapted
      for planning expansion cohorts. Recommendations for the size of expansion cohorts
      are proposed. Despite the exploratory character of the expansion cohort, a
      justification of their size based on assumptions statistically defined is
      recommended in order to provide an interpretable conclusion and to quantify the
      risk of errors.

PMID- 25609490
TI  - [Molecular biology of sarcoma and therapeutic choices].
AB  - Soft tissue sarcomas (STS) are a set of very heterogeneous tumors with numerous
      histological categories. The development of the molecular biology allowed
      identifying recurring molecular anomalies in certain subgroups of sarcomas, being
      able to represent diagnostic, prognosis and therapeutic tools. The molecular
      classification of STS includes until today 5 main groups of abnormalities:
      sarcomas with "simple genomic profile" showing reciprocal (1) chromosomal
      translocations, (2) activating mutation, (3) inhibitive mutation or (4) simple
      amplification; (5) sarcomas with "complex genomic profile" can include several
      tens of molecular abnormalities. The development of new-targeted therapies is
      based on the identification of a target, specific of a tumors subgroup and
      involved in carcinogenesis mechanisms and/or tumoral growth. Then, the aim of
      clinical research is to establish the proof of the concept through clinical
      trials, demonstrating the benefit brought to the patient and ending in the
      marketing of the drug. This proof of the concept was clearly established for
      imatinib, sunitinib and regorafenib in gastrointestinal stromal tumors, for
      imatinib in dermatofibrosarcoma protuberans and pigmented vilo-nodular synovitis,
      for denosumab in giant cell tumors of the bone, ending in the authorization to
      use these new therapies in these indications. It is in progress and promising for
      anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory
      tumors, for mTOR inhibitor in PEComas... The role of molecular abnormalities
      identified in the mechanisms of tumoral progress for sarcomas and their potential
      therapeutic impact will be detailed.

PMID- 25609491
TI  - [Metastatic hormone-sensitive prostate cancer].
AB  - The prostate cancer in its hormone-sensitive metastatic presentation is
      infrequent, it is either an initial presentation of the disease or an evolution
      after local treatment, without castration of the biological relapse. The surgical
      or biological castration remains the cornerstone of the treatment. The deadline
      of castration initiation and its modalities of administration, intermittent or
      continuous rest debated but consensual on the initiation is the appearance of the
      symptomatic disease. The chemotherapy by docetaxel in association with the
      castration increases significantly the survival of the patients having a high
      tumoral volume. The efficacy on the whole metastatic population requires
      additional analyses. Clinical prognostic factors as the bone localizations (axial
      or appendicular), the visceral involvement (liver, lung) are determining for the
      survival of these patients. Biological prognostic factors are in evaluation.
      Except the clodronate acid, which showed a survival improvement in the hormone
      sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the
      bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in
      castrate resistant metastatic prostate cancer (MCRPC). The management of local
      disease lets suggest a benefit to at least symptomatic disease, but it requires
      to be estimated prospectively in clinical trials. The new hormonal treatments
      targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The
      objective is to increase the survival and the quality of life of the CPMHS and to
      delay the evolution towards the castration resistant metastatic disease. 

PMID- 25609492
TI  - [Breaking immune tolerance in cancer].
AB  - The discovery and understanding of complex cellular interactions that govern the
      immune system contributed to the pharmacological targeting of anti-tumor
      immunity. The activity of immune effector cells, such as NK and T-cells, is
      regulated by a wide range of activating and inhibiting receptors or ligands.
      Drugs that target these receptors or ligands can modulate the immune response by
      exerting antagonistic or agonistic effects. Over the past decade, several
      immunomodulators have demonstrated clinical effectiveness, and three of them have
      already been approved for use in oncology. The development of these immunotherapy
      approaches presented unique challenges for safety and efficacy, requiring
      revising clinical response criteria and the establishment of guidelines to help
      oncologists to manage properly inflammatory toxicities. The introduction of these
      immunotherapies is a revolution in oncology. However, additional efforts in terms
      of optimizing treatment administration and identification of biomarkers are
      needed. Identifying the immunodynamics of various immunomodulators should allow a
      better understanding of anti-tumor and inflammatory mechanisms, and certainly
      give the opportunity to develop effective therapeutic combinations without
      potentiating adverse events. 

PMID- 25609493
TI  - [The stem cell niche in glioblastoma: from fundamental aspects to targeted
      therapies].
AB  - The concept of cancer stem cell (CSC) was established from models of
      leukemogenesis explaining tumor repopulation by the clonogenic properties of this
      specific population of tumoral cells. Among solid tumors, glioblastoma are
      currently the most documented models. Cancer stem cells reside in specific
      locations within tumors called niches. Anatomically, two complementary niches
      have been described in glioblastoma. The first one is a perivascular niche
      composed of vessels (endothelial cells, pericytes) and their microenvironment
      (integrins, interleukins) constitutive the nest of "normal" neural stem cells and
      cancer stem cells. The second one is a hypoxic niche found in regions with low
      oxygen tension such as the core of the tumor. In these niches, mutual
      interactions between CSC and their microenvironment involving the activation of
      multiple signaling pathways promote stemness maintenance and tumor propagation.
      The median overall survival of glioblastoma does not exceed 15 months despite an
      aggressive multimodal treatment, thus the therapeutic targeting of these niches,
      by systemic agents or radiotherapy, in order to inhibit the signaling pathways
      involved in the maintenance of the CSC niches, represents a major challenge. The
      combination of these two strategies appears promising and many clinical trials
      are underway. 

PMID- 25609494
TI  - Molecular dynamics simulations and statistical coupling analysis of GPI12 in L.
      major: functional co-evolution and conservedness reveals potential drug-target
      sites.
AB  - GPI12 represents an important enzyme in the GPI biosynthetic pathway of several
      parasites like 'Leishmania'. GPI activity is generally regulated through either
      the hindrance in GPI complex assembly formation or the modulation of the
      lipophosphoglycan (LPG) flux to either reduce or enhance the pathogenicity in an
      organism. Of the various GPI molecules known, GPI12 is an important enzyme in the
      GPI biosynthetic pathway which can be exploited as a target due to the substrate
      specificity difference in parasites and humans. In the present study, the
      functional importance of the co-evolving residues of the GPI12 protein of
      Leishmania has been highlighted using the GPI proteins belonging to the GlcNAC
      deacetylase family. Exploring the active site of the GPI12 protein and designing
      inhibitors against the functional residues provide ways and means to change the
      efficiency of deacetylation activity of the enzyme. The activity of de-N
      acetylase is low in the absence of metal ions like zinc. Hence we designed eight
      small molecules in order to modulate the activity of GPI12. Compound 8 was found
      to be an appropriate choice to target the agonist (GPI12) active site thereby
      targeting the residues which were essential in the Zn binding and chelation
      activity. Inhibition of these sites offered a strong constraint to block the
      protein activity and in turn GPI biosynthesis. 

PMID- 25609496
TI  - Clinical evaluation of semi-automatic landmark-based lesion tracking software for
      CT-scans.
AB  - BACKGROUND: To evaluate a semi-automatic landmark-based lesion tracking software
      enabling navigation between RECIST lesions in baseline and follow-up CT-scans.
      METHODS: The software automatically detects 44 stable anatomical landmarks in
      each thoraco/abdominal/pelvic CT-scan, sets up a patient specific coordinate
      system and cross-links the coordinate-systems of consecutive CT-scans. Accuracy
      of the software was evaluated on 96 RECIST lesions (target- and non-target
      lesions) in baseline and follow-up CT-scans of 32 oncologic patients (64 CT
      scans). Patients had to present at least one thoracic, one abdominal and one
      pelvic RECIST lesion. Three radiologists determined the deviation between
      lesions' centre and the software's navigation result in consensus. RESULTS: The
      initial mean runtime of the system to synchronize baseline and follow-up
      examinations was 19.4 +/- 1.2 seconds, with subsequent navigation to
      corresponding RECIST lesions facilitating in real-time. Mean vector length of the
      deviations between lesions' centre and the semi-automatic navigation result was
      10.2 +/- 5.1 mm without a substantial systematic error in any direction. Mean
      deviation in the cranio-caudal dimension was 5.4 +/- 4.0 mm, in the lateral
      dimension 5.2 +/- 3.9 mm and in the ventro-dorsal dimension 5.3 +/- 4.0 mm.
      CONCLUSION: The investigated software accurately and reliably navigates between
      lesions in consecutive CT-scans in real-time, potentially accelerating and
      facilitating cancer staging.

PMID- 25609497
TI  - Synthesis and characterization of FeCo nanowires with high coercivity.
AB  - Ferromagnetic FeCo nanocrystals with high coercivity have been synthesized using
      a reductive decomposition method. The sizes and shapes of the nanocrystals were
      found to be dependent on reaction parameters such as the surfactant ratio, the
      precursor concentration and the heating rate. Synthesized nanocrystals have a
      body-centered cubic crystal structure for both particles and nanowires and the
      (110) crystalline direction is along the long axis of the nanowires. The
      coercivity and magnetization of the FeCo nanocrystals are found to be dependent
      on morphology. Nanowires of Fe60Co40 with saturation magnetization of 92 emu g(
      1) and coercive force of 1.2 kOe have been obtained in this study. 

PMID- 25609495
TI  - Health worker perspectives on barriers to delivery of routine tuberculosis
      diagnostic evaluation services in Uganda: a qualitative study to guide clinic
      based interventions.
AB  - BACKGROUND: Studies of the quality of tuberculosis (TB) diagnostic evaluation of
      patients in high burden countries have generally shown poor adherence to
      international or national guidelines. Health worker perspectives on barriers to
      improving TB diagnostic evaluation are critical for developing clinic-level
      interventions to improve guideline implementation. METHODS: We conducted
      structured, in-depth interviews with staff at six district-level health centers
      in Uganda to elicit their perceptions regarding barriers to TB evaluation.
      Interviews were transcribed, coded with a standardized framework, and analyzed to
      identify emergent themes. We used thematic analysis to develop a logic model
      depicting health system and contextual barriers to recommended TB evaluation
      practices. To identify possible clinic-level interventions to improve TB
      evaluation, we categorized findings into predisposing, enabling, and reinforcing
      factors as described by the PRECEDE model, focusing on potentially modifiable
      behaviors at the clinic-level. RESULTS: We interviewed 22 health center staff
      between February 2010 and November 2011. Participants identified key health
      system barriers hindering TB evaluation, including: stock-outs of drugs/supplies,
      inadequate space and infrastructure, lack of training, high workload, low staff
      motivation, and poor coordination of health center services. Contextual barrier
      challenges to TB evaluation were also reported, including the time and costs
      borne by patients to seek and complete TB evaluation, poor health literacy, and
      stigma against patients with TB. These contextual barriers interacted with health
      system barriers to contribute to sub-standard TB evaluation. Examples of
      intervention strategies that could address these barriers and are related to
      PRECEDE model components include: assigned mentors/peer coaching for new staff
      (targets predisposing factor of low motivation and need for support to conduct
      job duties); facilitated workshops to implement same day microscopy (targets
      enabling factor of patient barriers to completing TB evaluation), and
      recognition/incentives for good TB screening practices (targets low motivation
      and self-efficacy). CONCLUSIONS: Our findings suggest that health system and
      contextual barriers work together to impede TB diagnosis at health centers and,
      if not addressed, could hinder TB case detection efforts. Qualitative research
      that improves understanding of the barriers facing TB providers is critical to
      developing targeted interventions to improve TB care.

PMID- 25609498
TI  - Epigenetic regulation of histone modifications and Gata6 gene expression induced
      by maternal diet in mouse embryoid bodies in a model of developmental
      programming.
AB  - BACKGROUND: Dietary interventions during pregnancy alter offspring fitness. We
      have shown mouse maternal low protein diet fed exclusively for the
      preimplantation period (Emb-LPD) before return to normal protein diet (NPD) for
      the rest of gestation, is sufficient to cause adult offspring cardiovascular and
      metabolic disease. Moreover, Emb-LPD blastocysts sense altered nutrition within
      the uterus and activate compensatory cellular responses including stimulated
      endocytosis within extra-embryonic trophectoderm and primitive endoderm (PE)
      lineages to protect fetal growth rate. However, these responses associate with
      later disease. Here, we investigate epigenetic mechanisms underlying nutritional
      programming of PE that may contribute to its altered phenotype, stabilised during
      subsequent development. We use embryonic stem (ES) cell lines established
      previously from Emb-LPD and NPD blastocysts that were differentiated into
      embryoid bodies (EBs) with outer PE-like layer. RESULTS: Emb-LPD EBs grow to a
      larger size than NPD EBs and express reduced Gata6 transcription factor
      (regulator of PE differentiation) at mRNA and protein levels, similar to Emb-LPD
      PE derivative visceral yolk sac tissue in vivo in later gestation. We analysed
      histone modifications at the Gata6 promoter in Emb-LPD EBs using chromatin
      immunoprecipitation assay. We found significant reduction in histone H3 and H4
      acetylation and RNA polymerase II binding compared with NPD EBs, all markers of
      reduced transcription. Other histone modifications, H3K4Me2, H3K9Me3 and
      H3K27Me3, were unaltered. A similar but generally non-significant histone
      modification pattern was found on the Gata4 promoter. Consistent with these
      changes, histone deacetylase Hdac-1, but not Hdac-3, gene expression was
      upregulated in Emb-LPD EBs. CONCLUSIONS: First, these data demonstrate ES cells
      and EBs retain and propagate nutritional programming adaptations in vitro,
      suitable for molecular analysis of mechanisms, reducing animal use. Second, they
      reveal maternal diet induces persistent changes in histone modifications to
      regulate Gata6 expression and PE growth and differentiation that may affect
      lifetime health.

PMID- 25609499
TI  - [Comparison of the specificity and sensitivity of various instrument-guided
      keratoconus indices and classifiers].
AB  - PURPOSE: Are the classifications achieved by the Belin-Ambrosio (BA) enhanced
      ectasia module, the keratoconus indices of the Pentacam HR and the ectasia
      screening index (ESI) using CASIA anterior segment optical coherence tomography
      (OCT) comparable to the topographical keratoconus classification (TKC) of the
      Pentacam HR? Can the indices be used interchangeably to assist in the diagnosis
      of keratoconus? METHODS: This retrospective study examined 228 datasets (eyes) of
      patients with a mean age of 36.6 +/- 13.6 years which were grouped into a non
      keratoconus group (group I, n = 59) and a keratoconus group (group II, n = 169)
      according to the clinical assessment. From the data sets of these eyes the
      sensitivity and specificity of various ectasia and keratoconus indices (KI) were
      calculated with the help of receiver operating characteristics (ROC). Groups were
      compared using the Mann-Whitney and chi(2)-tests. RESULTS: Groups I and II had a
      mean KI of 1.04 and 1.26 and a mean ESI of 3.0 and 66.6, respectively. The chi(2)
      test showed no significant coincidence of the distance of the thinnest point from
      the apex with TKC (chi(2) > 2, p > 0.35). All other BA parameters as well as the
      ESI showed a significant coincidence with the keratoconus diagnosis and the
      classification of TKC (p < 0.001). The ESI and KI along with some BA parameters
      (Df, Db, Dp and D) showed a good separation between groups I and II with an area
      under the ROC curves of > 0.93. CONCLUSION: The enhanced indices and classifiers,
      such as the BA module or the ESI were comparable with the purely anterior corneal
      surface based TKC.

PMID- 25609500
TI  - [Traumatic macular hole with central retinal detachment and choroidal rupture
      with ora serrata dialysis].
AB  - BACKGROUND: Closed ocular trauma is associated with various retinal
      complications, such as Berlin's edema, peripheral retinal tears, retinal
      hemorrhage, choroidal rupture, subretinal bleeding and macular holes. Traumatic
      macular holes (TMH) are rare and surgical intervention is controversial due to
      possible spontaneous closure. CASE REPORT: The positive development in the
      patient described here indicates that a pars plana vitrectomy with drainage of
      subretinal hemorrage combined with peeling of the internal limiting membrane
      (ILM) for a penetrating traumatic macular hole with choroidal rupture can lead to
      the restoration of visual acuity. The anti-vascular endothelial growth factor
      (VEGF) therapy (under silicone oil with avastin 0.02 ml) can successfully lead to
      limitation of posttraumatic choroidal neovascularization (CNV). CONCLUSIONS:
      Patients with ocular contusion require extensive long-term ophthalmological
      follow-up. Furthermore, prevention, education and information is essential to
      prevent serious injuries.

PMID- 25609501
TI  - Study protocol: transforming outcomes for patients through medical home
      evaluation and redesign: a cluster randomized controlled trial to test high value
      elements for patient-centered medical homes versus quality improvement.
AB  - BACKGROUND: Health care in the United States is in the midst of a near perfect
      storm: strong cost pressures, dramatic redesign efforts like patient-centered
      medical homes and accountable care organizations, and a broad series of payment
      and eligibility reforms. To date, alternative models of care intended to reduce
      costs and improve outcomes have shown mixed effects in the U.S., in part due to
      the difficulty of performing rigorous evaluation studies that control for the
      broader transformation while avoiding other biases, such as organizational or
      clinic effect on individual patient outcomes. Our objective is to test whether
      clinics assigned to achieve high value elements (HVEs) of practice redesign are
      more likely than controls to achieve improvements in patient health and
      satisfaction with care and reduction in costs. METHODS/DESIGN: To prepare, we
      interview stakeholders, align with health reform, and propose a pilot.
      Participants are primary care clinics engaged in reform. Study protocol requires
      that both arms receive monthly practice facilitation, IT-based milestone
      reporting, and small financial incentives based on self-determined quality
      improvement (QI) goals; intervention receives additional prompting to choose
      HVEs. Design is a cluster randomized controlled trial over 1 year with pre- and
      post-washout periods. Outcomes are unplanned utilization and costs, patient
      experience of care, quality, and team performance. Analysis is a multivariate
      difference-in-difference with adjustments for patient risk, intraclinic
      correlation, and other confounders. DISCUSSION: The TOPMED study is a cluster
      randomized controlled trial focused on learning how primary care practices can
      transform within health reform guidelines to achieve outcomes related to the
      Triple Aim. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT02106221.

PMID- 25609502
TI  - Erratum to: Endophthalmitis in Boston keratoprosthesis: case series and review of
      literature.
AB  - To report the clinical and microbiological characteristics of infectious
      endophthalmitis after Boston type I keratoprosthesis (B-K-Pro) implantation.
      Retrospective analysis of 45 eyes that received a B-K-Pro type 1 between 2009 and
      2012 was performed. Five eyes with a diagnosis of exogenous endophthalmitis after
      B-K-pro type 1 were identified and information about demographic data, indication
      for K-Pro, post-operative bandage contact lens use, post-operative prophylactic
      antibiotic use, timing and clinical presentation of endophthalmitis, gram stain
      and culture results of intraocular fluid and preoperative and post-operative
      visual acuity were collected. The incidence of endophthalmitis was 11.1 % (5 of
      45 eyes) and average time to develop endophthalmitis was 5.62 months (range 2
      days to 8 months). Mean patient age was 31.4 years (5 to 65 years). The surgical
      indications included corneal injury due to chemical burns (n = 2), multiple
      failed grafts secondary to microbial keratitis (n = 2) and congenital glaucoma
      with congenital herpetic keratitis (n = 1). Post-Boston K-Pro, the visual acuity
      ranged from light perception (LP) to 20/50. K-pro was explanted in 4 patients.
      There was bacterial and fungal growth in two patients each and one vitreous did
      not grow anything. All the eyes were phthisical at last visit. Infectious
      endophthalmitis after K-Pro implantation in our study had a higher incidence,
      early onset and extremely poor visual outcome compared with post-cataract surgery
      endophthalmitis, as reported in literature. Not only bacterial but also fungal
      infections are an important etiology for infectious endophthalmitis in these
      cases.

PMID- 25609503
TI  - National survey of back & neck pain amongst consultant ophthalmologists in the
      United Kingdom.
AB  - Repetitive tasks, awkward or prolonged working postures, and high cognitive load
      are risk factors for occupational musculoskeletal disorders. Ophthalmologists may
      be vulnerable given that they are exposed to a combination of these factors. This
      national study assesses the prevalence, severity and associations of back and
      neck pain amongst UK consultant ophthalmologists. A postal survey was conducted
      using addresses supplied by the Royal College of Ophthalmologists. Statistical
      analysis was performed using Pearson correlation coefficient, two-tailed
      probability testing, analysis of variance (ANOVA) and Dunn's multiple comparison
      test. 518 responses were received (50.3 % response rate). Back and neck pain were
      reported by 50.6 % (262/518) and 31.8 % (165/518) of respondents, respectively,
      with 62.4 % (323/518) reporting one or both. 33.6 % (174/518) reported pain
      whilst operating, of whom 78.7 % (137/174) found operating exacerbated their
      pain. 31.7 % (164/518) reported pain when using the slit lamp, of whom 71.3 %
      (117/164) found it exacerbated their pain. Individual subspecialties showed a
      significant relative risk of back or neck pain in some circumstances, when
      compared to ophthalmologists as a whole. Occupational back and neck pain remains
      a problem amongst ophthalmologists. Recommendations are made for modifications to
      the working environment, and consideration should be given to improving education
      for trainees.

PMID- 25609504
TI  - A novel virtual motor rehabilitation system for Guillain-Barre syndrome. Two
      single case studies.
AB  - INTRODUCTION: This article is part of the Focus Theme of Methods of Information
      in Medicine on "New Methodologies for Patients Rehabilitation". OBJECTIVES: For
      Guillain-Barre patients, motor rehabilitation programs are helpful at the onset
      to prevent the complications of paralysis and in cases of persistent motor
      impairment. Traditional motor rehabilitation programs may be tedious and
      monotonous, resulting in low adherence to the treatments. A Virtual Motor
      Rehabilitation system has been tested in Guillain-Barre patients to increase
      patient adherence and to improve clinical results. METHODS: Two people with
      Guillain-Barre performed 20 rehabilitation sessions. We tested a novel system
      based on Motor Virtual Rehabilitation in three periods of time (baseline
      evaluation, final evaluation, and follow-up. In the training program, the
      participants carried out a specific treatment using the Active Balance
      Rehabilitation system (ABAR). The system is composed of customizable virtual
      games to perform static and dynamic balance rehabilitation. RESULTS: Significant
      improvements in clinical results were obtained by both participants, with
      significant results in the static balance clinical test of the Anterior Reach
      test in the standing position and unipedal stance time. Other significant results
      were found in dynamic balance clinical tests in the Berg Balance Scale test and
      the 30-second Sit-to-Stand test. With regard to acceptance of the system, both
      patients enjoyed the experience, and both patients thought that this system was
      helpful for their rehabilitation. CONCLUSIONS: The results show that Virtual
      Motor Rehabilitation for Guillain-Barre patients provides clinical improvements
      in an entertaining way.

PMID- 25609505
TI  - [Melanoma: introduction and special demands on radiology].
AB  - CLINICAL ISSUE: The incidence of melanoma has rapidly increased in the last
      decades. Most relevant for patient prognosis is the tumor thickness, hence an
      early diagnosis is crucial. STANDARD TREATMENT: The basis of treatment is at the
      primary tumor stage and excision of regional metastases with curative intention.
      TREATMENT INNOVATIONS: Targeted therapies, such as BRAF and MEK inhibitors have
      the advantage of a rapid response even in highly advanced stages of the disease.
      DIAGNOSTIC WORK-UP: For routine diagnostics ultrasound, computed tomography (CT),
      fluorodeoxyglucose positron emission tomography CT (FDG-PET/CT) and magnetic
      resonance imaging (MRI) are used. PERFORMANCE AND ACHIEVEMENTS: In the treatment
      of distant metastases new treatment options are available which more than doubled
      patient survival rates. Especially immune therapies with immune checkpoint
      blockers, such as ipilimumab or PD-1 antibodies can lead to long-term survival of
      patients. In contrast to chemotherapy these new substances have characteristics
      which make new demands on radiologists related to the possibility of
      pseudoprogression in immune therapies, which make it necessary to use other
      response criteria. In addition, autoimmune phenomena, such as a sarcoid-like
      reactions may mimic new metastases and should be included in the differential
      diagnosis. BRAF inhibitors may lead to cystic conversions of metastases which
      again require an evaluation beyond the response evaluation criteria in solid
      tumors (RECIST), e.g. with the adapted Choi criteria. PRACTICAL RECOMMENDATIONS:
      Close interdisciplinary communication, functional imaging methods and adapted
      response criteria, such as the immune-related response criteria will optimize
      radiological evaluations of melanoma.

PMID- 25609506
TI  - [Systemic treatment of distant metastatic malignant melanoma].
AB  - CONTEXT: Systemic therapy of advanced metastatic malignant melanoma has been
      considerably changed by the approval of new drugs in recent years. The targeted
      therapy with the B-RAF inhibitors vemurafenib and dabrafenib achieves rapid tumor
      reduction but is often followed by the development of resistance in the further
      course of therapy. By immunotherapy with ipilimumab, on the other hand, a plateau
      effect becomes apparent in the survival curves. OBJECTIVE: The aim of this
      article is to discuss the treatment options for patients with advanced melanoma
      with special reference to new treatment options and substances for which approval
      is soon to be expected. METHODS: Treatment recommendations, taking into account
      the S3 guidelines on diagnosis, treatment and follow-up of melanoma and recent
      publications (Pubmed and manual search) are presented. RESULTS: In patients with
      B-RAF mutations, targeted therapy with the B-RAF inhibitor vemurafenib achieves
      response rates of 50-60 %, comparable with the B-RAF inhibitor dabrafenib, yet
      resistance often occurs after approximately 7 months. By immunotherapy with
      ipilimumab long-term survival can be achieved in approximately 20 % of patients.
      CONCLUSION: The treatment options for patients with metastatic melanoma have
      considerably improved in recent years. Several highly effective substances have
      recently become available and the approval of more potent substances is expected
      this year.

PMID- 25609507
TI  - Mental health in adolescence as determinant of alcohol consumption trajectories
      in the Northern Swedish Cohort.
AB  - OBJECTIVES: The study aimed to analyze whether poor mental health in adolescence
      predicts heavy alcohol consumption over the long term. METHODS: Alcohol
      consumption in the population cohort (n = 1010) was surveyed at the ages of 16,
      18, 21, 30 and 42. Utilizing latent class growth analysis, six consumption
      trajectories ranging from 'Late Onset Low' to 'Early Onset High' were defined and
      analyzed with respect to internalization (depressiveness and anxiousness) and
      externalization (truancy and vandalism) at age 16. RESULTS: Poor mental health
      predicted the Early Onset High trajectory (risk ratios in relation to the
      compliant trajectory 3.59 for anxiousness, 2.85 for depressiveness, 5.69 for
      truancy and 7.75 for externalized vandalism). Moreover, significant associations
      were found for the Early Onset Moderate and Early Onset Low trajectories.
      CONCLUSIONS: This is the first study to show an association between internalized
      mental health problems in adolescence and lifelong heavy drinking. The study also
      confirmed a strong association between externalized behavior and heavy drinking,
      indicating a need of preventive measures in this group. Nevertheless, the
      analyses demonstrated that most teenagers with mental health problems continue
      along a reasonable drinking trajectory.

PMID- 25609508
TI  - Editorial.

PMID- 25609509
TI  - Vortex formation time is not an index of ventricular function.
AB  - The diastolic intraventricular ring vortex formation and pinch-off process may
      provide clinically useful insights into diastolic function in health and disease.
      The vortex ring formation time (FT) concept, based on hydrodynamic experiments
      dealing with unconfined (large tank) flow, has attracted considerable attention
      and popularity. Dynamic conditions evolving within the very confined space of a
      filling, expansible ventricular chamber with relaxing and rebounding, and
      viscoelastic muscular boundaries diverge from unconfined (large tank) flow and
      encompass rebounding walls' suction and myocardial relaxation. Indeed,
      clinical/physiological findings seeking validation in vivo failed to support the
      notion that FT is an index of normal/abnormal diastolic ventricular function.
      Therefore, FT as originally proposed cannot and should not be utilized as such an
      index. Evidently, physiologically accurate models accounting for coupled
      hydrodynamic and (patho)physiological myocardial wall interactions with the
      intraventricular flow are still needed to enhance our understanding and yield
      diastolic function indices useful and reliable in the clinical setting. 

PMID- 25609510
TI  - Death and all its friends.

PMID- 25609512
TI  - Are 2 heads better than 1? Perspectives on job sharing in academic family
      medicine.

PMID- 25609513
TI  - Retraining family physicians to deliver our babies.

PMID- 25609515
TI  - Applause for case reports.

PMID- 25609516
TI  - Well-managed warfarin is superior to NOACs.

PMID- 25609517
TI  - Response.

PMID- 25609518
TI  - We stand by our conclusion.

PMID- 25609519
TI  - Approach to caring for developmentally disabled adults in the community: medical,
      ethical, and legal considerations.
AB  - OBJECTIVE: To review the medical, ethical, and legal obligations in caring for
      adults with developmental disabilities (DDs) living in the community. SOURCES OF
      INFORMATION: Google and MEDLINE searches were conducted using the terms disabled,
      disability, vulnerable, and community. The pertinent legislation was reviewed.
      MAIN MESSAGE: The treatment of a patient with DDs varies with factors such as the
      pathogenesis of the patient's current problem, comorbid conditions, the severity
      of his or her disabilities, and his or her current social supports. While the
      shift from institutional to community care for patients with DDs is widely
      accepted as being beneficial, providing high-quality community care has proven to
      be challenging. However, there is little research on how to effectively provide
      community support to adults with DDs. As primary care providers, family
      physicians are often the first point of contact for patients, and are responsible
      for both the coordination and the continuity of care. With the movement toward
      preventive care and early disease detection, the patient's active participation
      is also vital. The patient's values and goals are an essential consideration,
      even when they are contrary to the patient's good health or the clinician's own
      values. The legislation for vulnerable persons varies among the provinces. Thus,
      the obligation to report suspected abuse might depend on whether the vulnerable
      person is living in a care facility or the community; whether the person with the
      suspicion is a service provider or health care professional; and whether the
      specific circumstances fall within the legislative definition of abuse or
      neglect. CONCLUSION: Primary care providers must give adults with DDs
      compassionate care that respects the patients' wishes.

PMID- 25609520
TI  - Inhalation injury.

PMID- 25609521
TI  - HPV vaccine for cancer and wart prevention.

PMID- 25609522
TI  - Contributors to primary care guidelines: What are their professions and how many
      of them have conflicts of interest?
AB  - OBJECTIVE: To determine the professions of those who contribute to guidelines,
      guideline variables associated with differing contributor participation, and
      whether conflict of interest statements are provided in primary care guidelines.
      DESIGN: Retrospective analysis of the primary care guidelines from the Canadian
      Medical Association website. Two independent data extractors reviewed the
      guidelines and extracted relevant data. SETTING: Canada. MAIN OUTCOME MEASURES:
      Sponsors of guidelines, jurisdiction (national or provincial) of guidelines, the
      professions of those who contribute to guidelines, and the reported conflict of
      interest statements within guidelines. RESULTS: Of the 296 guidelines in the
      family medicine section of the CMA Infobase, 65 were duplicates and 35 had
      limited relevance to family medicine. Twenty did not provide contributor
      information, leaving 176 guidelines for analysis. In total, there were 2495
      contributors (authors and committee members): 1343 (53.8%) non-family physician
      specialists, 423 (17.0%) family physicians, 141 (5.7%) nurses, 75 (3.0%)
      pharmacists, 269 (10.8%) other clinicians, 203 (8.1%) nonclinician scientists,
      and 41 (1.6%) unknown professions. The proportion of contributors from the
      various professions differed significantly between provincial and national
      guidelines, as well as between industry-funded and non-industry-funded guidelines
      (both P < .001). For provincial guidelines, 30.8% of contributors were family
      physicians and 37.3% were other specialists compared with 13.9% and 57.4%,
      respectively, for national guidelines. Of industry-funded guidelines, 7.8% of
      contributors were family physicians and 68.6% were other specialists compared
      with 19.4% and 49.9%, respectively, for non-industry-funded guidelines. Conflicts
      of interest were not reported in 68.9% of guidelines. When reported, conflict of
      interest statements were present for 48.6% of non-family physician specialists,
      30.0% of pharmacists, 27.7% of family physicians, and 10.0% or less of the
      remaining groups; differences were statistically significant (P < .001).
      CONCLUSION: Non-family physician specialists outnumber all other health care
      providers combined and are more than 3 times more likely to contribute to primary
      care guidelines than family physicians are. Conflict of interest statements were
      provided in the minority of guidelines, and for guidelines in which conflict of
      interest statements were included, non-family physician specialists were most
      likely to report them. Guidelines targeted to primary care should have much more
      primary care and family medicine representation and include fewer contributors
      who have conflicts of interest.

PMID- 25609524
TI  - Only life.

PMID- 25609525
TI  - Lessons in teaching.

PMID- 25609527
TI  - Dr Jaco Kruger MD CCFP.

PMID- 25609529
TI  - Using EMRs to fuel quality improvement.

PMID- 25609530
TI  - Sitting and thinking.

PMID- 25609533
TI  - Farewell to Inese Grava-Gubins.

PMID- 25609535
TI  - Sunsets.

PMID- 25609538
TI  - Mission.

PMID- 25609539
TI  - Adoption of an advanced access model by residents: pilot project at the Gaspe
      family practice unit.

PMID- 25609541
TI  - Are you ready for an office code blue? : online video to prepare for office
      emergencies.
AB  - PROBLEM BEING ADDRESSED: Medical emergencies occur commonly in offices of family
      physicians, yet many offices are poorly prepared for emergencies. An Internet
      based educational video discussing office emergencies might improve the responses
      of physicians and their staff to emergencies, yet such a tool has not been
      previously described. OBJECTIVE OF PROGRAM: To use evidence-based practices to
      develop an educational video detailing preparation for emergencies in medical
      offices, disseminate the video online, and evaluate the attitudes of physicians
      and their staff toward the video. PROGRAM DESCRIPTION: A 6-minute video was
      created using a review of recent literature and Canadian regulatory body
      policies. The video describes recommended emergency equipment, emergency response
      improvement, and office staff training. Physicians and their staff were invited
      to view the video online at www.OfficeEmergencies.ca. Viewers' opinions of the
      video format and content were assessed by survey (n = 275). CONCLUSION: Survey
      findings indicated the video was well presented and relevant, and the Web-based
      format was considered convenient and satisfactory. Participants would take other
      courses using this technology, and agreed this program would enhance patient
      care.

PMID- 25609542
TI  - Magnetic-activated cell sorting (MACS) can be used as a large-scale method for
      establishing zebrafish neuronal cell cultures.
AB  - Neuronal cell cultures offer a crucial tool to mechanistically analyse
      regeneration in the nervous system. Despite the increasing importance of
      zebrafish (Danio rerio) as an in vivo model in neurobiological and biomedical
      research, in vitro approaches to the nervous system are lagging far behind and no
      method is currently available for establishing enriched neuronal cell cultures.
      Here we show that magnetic-activated cell sorting (MACS) can be used for the
      large-scale generation of neuronal-restricted progenitor (NRP) cultures from
      embryonic zebrafish. Our findings provide a simple and semi-automated method that
      is likely to boost the use of neuronal cell cultures as a tool for the
      mechanistic dissection of key processes in neuronal regeneration and development.

PMID- 25609544
TI  - Tropical Atlantic temperature seasonality at the end of the last interglacial.
AB  - The end of the last interglacial period, ~118 kyr ago, was characterized by
      substantial ocean circulation and climate perturbations resulting from
      instabilities of polar ice sheets. These perturbations are crucial for a better
      understanding of future climate change. The seasonal temperature changes of the
      tropical ocean, however, which play an important role in seasonal climate
      extremes such as hurricanes, floods and droughts at the present day, are not well
      known for this period that led into the last glacial. Here we present a monthly
      resolved snapshot of reconstructed sea surface temperature in the tropical North
      Atlantic Ocean for 117.7+/-0.8 kyr ago, using coral Sr/Ca and delta(18)O records.
      We find that temperature seasonality was similar to today, which is consistent
      with the orbital insolation forcing. Our coral and climate model results suggest
      that temperature seasonality of the tropical surface ocean is controlled mainly
      by orbital insolation changes during interglacials. 

PMID- 25609543
TI  - Organization of the mitochondrial translation machinery studied in situ by
      cryoelectron tomography.
AB  - Whereas the structure and function of cytosolic ribosomes have been studied in
      great detail, we know surprisingly little about the structural basis of
      mitochondrial protein synthesis. Here we used cryoelectron tomography and
      subtomogram analysis to visualize mitoribosomes in isolated yeast mitochondria,
      avoiding perturbations during ribosomal purification. Most mitoribosomes reside
      in immediate proximity to the inner mitochondrial membrane, in line with their
      specialization in the synthesis of hydrophobic membrane proteins. The subtomogram
      average of membrane-associated mitoribosomes reveals two distinct membrane
      contact sites, formed by the 21S rRNA expansion segment 96-ES1 and the inner
      membrane protein Mba1. On the basis of our data, we further hypothesize that Mba1
      is not just a passive mitoribosome receptor on the inner membrane, but that it
      spatially aligns mitoribosomes with the membrane insertion machinery. This study
      reveals detailed insights into the supramolecular organization of the
      mitochondrial translation machinery and its association with the inner membrane
      in translation-competent mitochondria. 

PMID- 25609545
TI  - Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation
      and predicts outcome in patients with mucosal melanoma.
AB  - BACKGROUND: In patients with metastatic melanoma and KIT amplifications and/or
      mutations, therapy with imatinib mesylate may prolong survival. 18F-labeled 2
      fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT may be used to assess metabolic
      response. We investigated associations of metabolic response, mutational status,
      progression-free survival and overall survival in this population. METHODS:
      Baseline and 4-week follow-up 18F-FDG-PET/CT were evaluated in 17 patients with
      metastatic melanoma and KIT amplifications and/or mutations treated with imatinib
      in a multicenter phase II clinical trial. The maximum standardized uptake values
      (SUVmax) were measured in up to 10 lesions on each scan. Metabolic response was
      classified using modified EORTC criteria. Each patient had a diagnostic CT or MR
      at baseline, after 6 weeks of therapy and then at intervals of 2 months and
      anatomic response was classified using RECIST 1.0. Median follow-up was 9.8
      months. RESULTS: Partial metabolic response (PMR), stable metabolic disease (SMD)
      and progressive metabolic disease (PMD) was seen in 5 (29%), 5 (29%), and 7 (41%)
      patients respectively. Five patients (29%) had a KIT mutation in exon 11, four of
      whom (80%) had PMR while 1 (20%) had SMD. Twelve patients (71%) did not have a
      KIT mutation in exon 11, and only 1 (8%) had PMR, 4 (33%) had SMD and 7 (58%) had
      PMD. There was agreement of metabolic and anatomic classification in 12 of 17
      patients (71%). Four of 17 patients (24%) had PR on both metabolic and anatomic
      imaging and all had a KIT mutation in exon 11. Survival of patients with PMD was
      lower than with SMD or PMR. CONCLUSIONS: Metabolic response by 18F-FDG-PET/CT is
      associated with mutational status in metastatic melanoma patients treated with
      imatinib. 18F-FDG-PET/CT may be a predictor of outcome, although a larger study
      is needed to verify this. CLINICAL TRIAL REGISTRATION: NCT00424515.

PMID- 25609546
TI  - The possible role of percutaneous tibial nerve stimulation using adhesive skin
      surface electrodes in patients with neurogenic detrusor overactivity secondary to
      spinal cord injury.
AB  - PURPOSE: To compare the effectiveness of percutaneous tibial nerve stimulation
      (PTNS) using adhesive skin surface electrodes versus solifenacin succinate (SS)
      in patients with neurogenic detrusor overactivity (NDO) secondary to spinal cord
      injury (SCI). METHODS: A randomized controlled study involving 100 patients with
      NDO secondary to SCI was conducted. Patients were randomized into two groups. In
      group A, patients received PTNS using adhesive skin surface electrodes for 4
      weeks. In group B, patients underwent SS treatment for 4 weeks. Bladder diaries
      and incontinence quality of life questionnaire were reviewed before treatment and
      2 and 4 weeks after treatment. RESULTS: Improvement in all bladder diary
      parameters was statistically significant within each group 2 and 4 weeks after
      treatment compared to baseline (p < 0.05), but did not reach statistical
      significance between the PTNS and SS groups (p > 0.05). Compared to SS, PTNS was
      not associated with any unanticipated adverse events. CONCLUSIONS: PTNS therapy
      with adhesive skin surface electrodes is an effective method to treat NDO
      secondary to SCI. This therapy is not only no difference comparing to SS therapy
      but also noninvasive and easily managed by patients.

PMID- 25609547
TI  - Comprehensive utilization of the pyrolysis products from sewage sludge.
AB  - Bio-oils were produced from pyrolysis of sewage sludge in a horizontal tubular
      furnace under the anoxic or anaerobic conditions, by varying operating parameters
      and moisture content (MC) of the feedstock. Physicochemical properties of the
      obtained bio-oil (such as density, acid value, kinematical viscosity, high
      heating value and flash point) were analysed and compared with Chinese fuel
      standards. Tend, RT and beta were found critical to control the yield and physico
      chemical properties of bio-oil products. The relative importance of various
      parameters such as Tend, RT, beta and MC was determined and the optimum values
      for the lowest kinematic viscosity and acid value and the highest yield of the
      bio-oil were achieved using the orthogonal matrix method. The parameters 550
      degrees C, 45 min, 5 degrees C min(-1) and MC of 10% were found effective in
      producing the bio-oils with most of the desirable physico-chemical properties and
      yield. Benefit analysis was conducted to further optimize the operating
      parameters, considering pyrolysis treatment, comprehensive utilization of the
      pyrolysis products and final disposal of sewage sludge; the results showed the
      best economy of the pyrolysis parameters 450 degrees C, 75 min, 3 degrees C min(
      1) and MC of 10%. The char obtained under this condition may serve as a
      microporous liquid adsorbent, while the bio-oil may serve as a low grade fuel oil
      after upgrading it with conventional fuel oil and deacidification. Pyrolysis
      products may become economically competitive in addition to being environment
      friendly. 

PMID- 25609548
TI  - A highly stable indium phosphonocarboxylate framework as a multifunctional sensor
      for Cu(2+) and methylviologen ions.
AB  - An indium phosphonocarboxylate framework, {H3O[In(pbpdc)].3H2O}n (InPCF-1) (pbpdc
      = 4'-phosphonobiphenyl-3,5-dicarboxylate), was hydrothermally synthesized. The
      structure of InPCF-1 features the inorganic chains as rod-shaped second building
      units. The rod-packing arrangement results in a three-dimensional (3-D) framework
      with a novel (3,4,5)-connected net. Studies of the gas adsorption, and thermal
      and chemical stability of InPCF-1 demonstrated its adsorption capacity for CO2,
      selective separation of CO2 over O2 and N2, high thermal stability, and a
      remarkable chemical resistance to boiling water, ethyl alcohol, and
      methylbenzene. Importantly, InPCF-1 shows a selective and sensitive response to
      Cu(2+) ions. It also serves as a sensor for methylviologen. 

PMID- 25609549
TI  - A randomized study of raisins versus alternative snacks on glycemic control and
      other cardiovascular risk factors in patients with type 2 diabetes mellitus.
AB  - Just as the type and duration of physical activity can have variable effects on
      the glucose levels and other cardiometabolic parameters among patients with type
      2 diabetes mellitus (T2DM), so can the types of foods have variable effects as
      well. This 12-week randomized study of 51 study participants evaluated the impact
      of routine consumption of dark raisins versus alternative processed snacks on
      glucose levels and other cardiovascular risk factors among patients with type
      T2DM. In this study, compared to alternative processed snacks, those who consumed
      raisins had a significant 23% reduction in postprandial glucose levels (P =
      0.024). Also compared to snacks, those who consumed raisins had a 19% reduction
      in fasting glucose and 0.12% reduction in hemoglobin A1c, although these latter
      findings did not achieve statistical significance. Regarding blood pressure,
      compared to alternative processed snacks, those who consumed raisins had a
      significant 8.7 mmHg reduction in systolic blood pressure (P = 0.035) (7.5% [P =
      0.031]) but did not experience a significant reduction in diastolic blood
      pressure. Compared to alternative processed snacks, those who consumed raisins
      did not have a significant improvement in body weight, body mass index, waist
      circumference, fasting insulin, homeostatic model assessment of insulin
      resistance, total cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol (HDL), triglyceride, or non-HDL cholesterol levels.
      Overall, these data support raisins as a healthy alternative compare to processed
      snacks in patients with T2DM.

PMID- 25609550
TI  - A simple microfluidic assay for the detection of ligation product.
AB  - We present a novel microfluidic-based approach to detect ligation products. The
      conformal specificity of ligases is used in various molecular assays to detect
      point mutations. Traditional methods of detecting ligation products include
      denaturing gel electrophoresis, sequence amplification, and melting curve
      analysis. Gel electrophoresis is a labor- and time-intensive process, while
      sequence amplification and melting curve analysis require instruments capable of
      accurate thermal ramping and sensitive optical detection. Microfluidics has been
      widely applied in genomics, proteomics, and cell cytometry to enable rapid and
      automated assays. We designed an assay that fluorogenically detects ligation
      products following a simple magnetic separation through a microfluidic channel.
      100 nM of synthetic HIV-1 K103N minority mutant templates were successfully
      detected in 30 min. This simple and rapid method can be coupled with any ligation
      assay for the detection of ligation products.

PMID- 25609552
TI  - Aqueous organic chemistry in the atmosphere: sources and chemical processing of
      organic aerosols.
AB  - Over the past decade, it has become clear that aqueous chemical processes
      occurring in cloud droplets and wet atmospheric particles are an important source
      of organic atmospheric particulate matter. Reactions of water-soluble volatile
      (or semivolatile) organic gases (VOCs or SVOCs) in these aqueous media lead to
      the formation of highly oxidized organic particulate matter (secondary organic
      aerosol; SOA) and key tracer species, such as organosulfates. These processes are
      often driven by a combination of anthropogenic and biogenic emissions, and
      therefore their accurate representation in models is important for effective air
      quality management. Despite considerable progress, mechanistic understanding of
      some key aqueous processes is still lacking, and these pathways are incompletely
      represented in 3D atmospheric chemistry and air quality models. In this article,
      the concepts, historical context, and current state of the science of aqueous
      pathways of SOA formation are discussed.

PMID- 25609553
TI  - Nutrition and cancer - global and African perspectives: a focused update.
AB  - The burden of cancer worldwide is predicted to almost double by 2030 to nearly 23
      million cases annually. The great majority of this increase is expected to occur
      in less economically developed countries, where access to expensive medical,
      surgical and radiotherapeutic interventions is likely to be limited to a small
      proportion of the population. This emphasises the need for preventive measures,
      as outlined in the declaration from the United Nations 2011 High Level Meeting on
      Non-communicable Diseases. The rise in incidence is proposed to follow from
      increasing numbers of people reaching middle and older ages, together with
      increasing urbanisation of the population with a nutritional transition from
      traditional diets to a more globalised 'Western' pattern, with a decrease in
      physical activity. This is also expected to effect a change in the pattern of
      cancers from a predominantly smoking and infection dominated one, to a smoking
      and obesity dominated one. The World Cancer Research Fund estimates that about a
      quarter to a third of the commonest cancers are attributable to excess body
      weight, physical inactivity and poor diet, making this the most common cause of
      cancers after smoking. These cancers are potentially preventable, but knowledge
      of the causes of cancer has not led to effective policies to prevent the export
      of a 'Western' pattern of cancers in lower income countries such as many in
      Africa. 

PMID- 25609551
TI  - Genomes of the rice pest brown planthopper and its endosymbionts reveal complex
      complementary contributions for host adaptation.
AB  - BACKGROUND: The brown planthopper, Nilaparvata lugens, the most destructive pest
      of rice, is a typical monophagous herbivore that feeds exclusively on rice sap,
      which migrates over long distances. Outbreaks of it have re-occurred
      approximately every three years in Asia. It has also been used as a model system
      for ecological studies and for developing effective pest management. To better
      understand how a monophagous sap-sucking arthropod herbivore has adapted to its
      exclusive host selection and to provide insights to improve pest control, we
      analyzed the genomes of the brown planthopper and its two endosymbionts. RESULTS:
      We describe the 1.14 gigabase planthopper draft genome and the genomes of two
      microbial endosymbionts that permit the planthopper to forage exclusively on rice
      fields. Only 40.8% of the 27,571 identified Nilaparvata protein coding genes have
      detectable shared homology with the proteomes of the other 14 arthropods included
      in this study, reflecting large-scale gene losses including in evolutionarily
      conserved gene families and biochemical pathways. These unique genomic features
      are functionally associated with the animal's exclusive plant host selection.
      Genes missing from the insect in conserved biochemical pathways that are
      essential for its survival on the nutritionally imbalanced sap diet are present
      in the genomes of its microbial endosymbionts, which have evolved to complement
      the mutualistic nutritional needs of the host. CONCLUSIONS: Our study reveals a
      series of complex adaptations of the brown planthopper involving a variety of
      biological processes, that result in its highly destructive impact on the
      exclusive host rice. All these findings highlight potential directions for
      effective pest control of the planthopper.

PMID- 25609555
TI  - The Arabidopsis transcription factor BRASSINOSTEROID INSENSITIVE1-ETHYL
      METHANESULFONATE-SUPPRESSOR1 is a direct substrate of MITOGEN-ACTIVATED PROTEIN
      KINASE6 and regulates immunity.
AB  - Pathogen-associated molecular patterns (PAMPs) are recognized by plant pattern
      recognition receptors to activate PAMP-triggered immunity (PTI). Mitogen
      activated protein kinases (MAPKs), as well as other cytoplasmic kinases,
      integrate upstream immune signals and, in turn, dissect PTI signaling via
      different substrates to regulate defense responses. However, only a few direct
      substrates of these signaling kinases have been identified. Here, we show that
      PAMP perception enhances phosphorylation of BRASSINOSTEROID INSENSITIVE1-ETHYL
      METHANESULFONATE-SUPPRESSOR1 (BES1), a transcription factor involved in
      brassinosteroid (BR) signaling pathway, through pathogen-induced MAPKs in
      Arabidopsis (Arabidopsis thaliana). BES1 interacts with MITOGEN-ACTIVATED PROTEIN
      KINASE6 (MPK6) and is phosphorylated by MPK6. bes1 loss-of-function mutants
      display compromised resistance to bacterial pathogen Pseudomonas syringae pv
      tomato DC3000. BES1 S286A/S137A double mutation (BES1(SSAA)) impairs PAMP-induced
      phosphorylation and fails to restore bacterial resistance in bes1 mutant,
      indicating a positive role of BES1 phosphorylation in plant immunity. BES1 is
      phosphorylated by glycogen synthase kinase3 (GSK3)-like kinase BR-insensitive2
      (BIN2), a negative regulator of BR signaling. BR perception inhibits BIN2
      activity, allowing dephosphorylation of BES1 to regulate plant development.
      However, BES1(SSAA) does not affect BR-mediated plant growth, suggesting
      differential residue requirements for the modulation of BES1 phosphorylation in
      PTI and BR signaling. Our study identifies BES1 as a unique direct substrate of
      MPK6 in PTI signaling. This finding reveals MAPK-mediated BES1 phosphorylation as
      another BES1 modulation mechanism in plant cell signaling, in addition to GSK3
      like kinase-mediated BES1 phosphorylation and F box protein-mediated BES1
      degradation.

PMID- 25609557
TI  - Cost-effectiveness of adding rituximab to splenectomy and romiplostim for
      treating steroid-resistant idiopathic thrombocytopenic purpura in adults.
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in
      which the platelet count falls to <100 * 10(9)/L. Corticosteroids are recommended
      as the first-line treatment, splenectomy is recommended as the second-line
      treatment, and thrombopoietin receptor agonists (TPO-RAs) and rituximab are
      recommended as the third-line treatments for ITP in Japanese ITP treatment
      guidelines. However, in Japan, rituximab is not eligible for reimbursement for
      the treatment of ITP. The cost-effectiveness of ITP treatment has not been
      investigated in Japan. Therefore, in this study, the cost-effectiveness of adding
      rituximab treatment to the existing treatments indicated for ITP in Japan, namely
      splenectomy and the TPO-RA romiplostim, was investigated based on the scenario
      that rituximab is eligible for reimbursement in Japan as a treatment for ITP.
      METHODS: The efficacy endpoint was set as the number of years with a platelet
      count >=30 * 10(9)/L. The analysis was conducted from the healthcare payer's
      perspective. If the first treatment is ineffective or relapse occurs, then the
      patient is given the following treatment. The analyzed treatment order consisted
      of three patterns: splenectomy-romiplostim (sequence 1), splenectomy-romiplostim
      rituximab (sequence 2), and splenectomy-rituximab-romiplostim (sequence 3). A
      Markov model was built for ITP, and the analysis period was set as 2 years. The
      discount rate was an annual rate of 2%. Sensitivity analyses of the efficacy of
      splenectomy, romiplostim, and rituximab; treatment cost; and romiplostim dose
      were performed. RESULTS: The expected costs per patient over a 2-year period for
      sequences 1, 2, and 3 were USD 40,980, USD 39,822, and USD 33,551, respectively.
      The expected years with a platelet count >=30 * 10(9)/L for the three sequences
      were 1.75, 1.79, and 1.78 years, respectively. The sensitivity analyses
      illustrated that the results of the base case analysis were robust. CONCLUSIONS:
      Adding rituximab to standard treatment for ITP (sequences 2-3) is less costly and
      marginally more effective than standard therapy in adults. According to the study
      results, if rituximab is reimbursed for the treatment of ITP in Japan, medical
      expenses are expected to decline.

PMID- 25609556
TI  - SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE2.6, an ortholog of OPEN STOMATA1,
      is a negative regulator of strawberry fruit development and ripening.
AB  - Whereas the regulatory mechanisms that direct fruit ripening have been studied
      extensively, little is known about the signaling mechanisms underlying this
      process, especially for nonclimacteric fruits. In this study, we demonstrated
      that a SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE2, designated as FaSnRK2.6,
      is a negative regulator of fruit development and ripening in the nonclimacteric
      fruit strawberry (Fragaria * ananassa) and can also mediate temperature-modulated
      strawberry fruit ripening. FaSnRK2.6 was identified as an ortholog of OPEN
      STOMATA1. Levels of FaSnRK2.6 transcript rapidly decreased during strawberry
      fruit development and ripening. FaSnRK2.6 was found to be capable of physically
      interacting with strawberry ABSCISIC ACID INSENSITIVE1, a negative regulator in
      strawberry fruit ripening. RNA interference-induced silencing of FaSnRK2.6
      significantly promoted fruit ripening. By contrast, overexpression of FaSnRK2.6
      arrested fruit ripening. Strawberry fruit ripening is highly sensitive to
      temperature, with high temperatures promoting ripening and low temperatures
      delaying it. As the temperature increased, the level of FaSnRK2.6 expression
      declined. Furthermore, manipulating the level of FaSnRK2.6 expression altered the
      expression of a variety of temperature-responsive genes. Taken together, this
      study demonstrates that FaSnRK2.6 is a negative regulator of strawberry fruit
      development and ripening and, furthermore, that FaSnRK2.6 mediates temperature
      modulated strawberry fruit ripening.

PMID- 25609558
TI  - Nanostructure of mixtures of protic ionic liquids and lithium salts: effect of
      alkyl chain length.
AB  - The bulk structure of mixtures of two protic ionic liquids, propylammonium
      nitrate and butylammonium nitrate, with a salt with a common anion, is analyzed
      at room temperature by means of small angle X-ray scattering and classical
      molecular dynamics simulations. The study of several structural properties, such
      as density, radial distribution functions, spatial distribution functions,
      hydrogen bonds, coordination numbers and velocity autocorrelation functions,
      demonstrates that increasing the alkyl chain length of the alkylammonium cation
      results in more segregated, better defined polar and apolar domains, the latter
      having a larger size. This increase, ascribed to the erosion of the H-bond
      network in the ionic liquid polar regions as salt is added, is confirmed by means
      of small angle X-ray scattering measurements, which show a clear linear increase
      of the characteristic spatial sizes of the studied protic ionic liquids with salt
      concentration, similar to that previously reported for ethylammonium nitrate (J.
      Phys. Chem. B, 2014, 118, 761-770). In addition, larger ionic liquid cations lead
      to a lower degree of hydrogen bonding and to more sparsely packed three
      dimensional structures, which are more easily perturbed by the addition of
      lithium salts. 

PMID- 25609559
TI  - Mobile phone text messaging interventions for HIV and other chronic diseases: an
      overview of systematic reviews and framework for evidence transfer.
AB  - BACKGROUND: Strong international commitment and the widespread use of
      antiretroviral therapy have led to higher longevity for people living with human
      immune deficiency virus (HIV). Text messaging interventions have been shown to
      improve health outcomes in people living with HIV. The objectives of this
      overview were to: map the state of the evidence of text messaging interventions,
      identify knowledge gaps, and develop a framework for the transfer of evidence to
      other chronic diseases. METHODS: We conducted a systematic review of systematic
      reviews on text messaging interventions to improve health or health related
      outcomes. We conducted a comprehensive search of PubMed, EMBASE (Exerpta Medica
      Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature),
      PsycINFO, Web of Science (WoS) and the Cochrane Library on the 17th April 2014.
      Screening, data extraction and assessment of methodological quality were done in
      duplicate. Our findings were used to develop a conceptual framework for transfer.
      RESULTS: Our search identified 135 potential systematic reviews of which nine
      were included, reporting on 37 source studies, conducted in 19 different
      countries. Seven of nine (77.7%) of these reviews were high quality. There was
      some evidence for text messaging as a tool to improve adherence to antiretroviral
      therapy. Text messages also improved attendance at appointments and behaviour
      change outcomes. The findings were inconclusive for self-management of illness,
      treatment of tuberculosis and communicating results of medical investigations.
      The geographical distribution of text messaging research was limited to specific
      regions of the world. Prominent knowledge gaps included the absence of data on
      long term outcomes, patient satisfaction, and economic evaluations. The included
      reviews also identified methodological limitations in many of the primary
      studies. CONCLUSIONS: Global evidence supports the use of text messaging as a
      tool to improve adherence to medication and attendance at scheduled appointments.
      Given the similarities between HIV and other chronic diseases (long-term
      medications, life-long care, strong link to behaviour and the need for home-based
      support) evidence from HIV may be transferred to these diseases using our
      proposed framework by integration of HIV and chronic disease services or direct
      transfer.

PMID- 25609560
TI  - Relationships between mild PM10 and ozone urban air levels and spontaneous
      abortion: clues for primary prevention.
AB  - The effects of environmental pollution on spontaneous abortion (SAB) are still
      unclear. Records of SAB were collected from five cities (514,996 residents) and
      correlated with PM10, NO(2) and ozone levels. Median pollutant concentrations
      were below legal limits. Monthly SABs positively correlated with PM10 and ozone
      levels but not with NO(2) levels. The mean monthly SAB rate increase was
      estimated equal to 19.7 and 33.6 % per 10 MUg/m(3) increase in PM10 or ozone
      concentration, respectively. Higher values of PM10 and SABs were evident in
      cities with- than in those without pollutant industries, with a number of SABs
      twofolds higher in the former group. In conclusion, SAB occurrence is affected by
      PM10 (particularly if industrial areas are present) and ozone concentrations,
      also at levels below the legal limits. Thus, SAB might be considered, at least in
      part, a preventable condition.

PMID- 25609561
TI  - Validating the alkene and alkyne hydrophosphonylation as an entry to
      organophosphonates.
AB  - The first paper on the hydrophosphonylation of terminal alkenes was published in
      1958 by Stiles and coworkers. Afterwards various papers described organometal
      catalyzed and free-radical reactions leading to linear anti-Markovnikov adducts
      and/or branched Markovnikov products. In 1996 Han and Tanaka reported the first
      example of alkyne hydrophosphonylation catalyzed by a palladium complex. Further
      studies using other metal catalysts registered poor selectivity as mixtures of
      adducts were obtained in most of the cases examined. The first example of alkyne
      hydrophosphonylation by H-phosphonates under free-radical conditions leading to Z
      and E-vinylphosphonates in a 1 : 1 ratio was reported by our group.
      Nevertheless, Z- to E-isomerization took place upon irradiation in the presence
      of a thiol. 

PMID- 25609562
TI  - The effect of fast eating on the thermic effect of food in young Japanese women.
AB  - The relationship between eating speed and the thermic effect of food (TEF)
      remains unclear. We investigated the difference in the TEF when meals containing
      the same amount of energy were eaten in 5 min (fast eating) or 15 min (regular
      eating). Subjects were nine non-obese young women. Following a 350 kcal (1464 kJ)
      meal, energy expenditure and autonomic nervous system activity were measured. The
      frequency of mastication was also calculated. The TEF for the 15-min period after
      the start of eating with fast eating was significantly lower than with regular
      eating (p < 0.01). There was a significant positive correlation between the low
      frequency/high-frequency ratio and TEF at 5-min intervals up to 20 min after the
      start of eating and between total mastication frequency and TEF during ingestion.
      Fast eating may reduce the TEF, potentially because a decrease in mastication
      frequency decreases sympathetic nervous system activity.

PMID- 25609563
TI  - Brassinosteroids alleviate high-temperature injury in Ficus concinna seedlings
      via maintaining higher antioxidant defence and glyoxalase systems.
AB  - Although brassinosteroids (BRs) play crucial roles in plant development and
      stress tolerance, the mechanisms by which they have these effects are poorly
      understood. Here, we investigated the possible mechanism of exogenously applied
      BRs on reactive oxygen species (ROS), antioxidant defence and methylglyoxal (MG)
      detoxification systems in Ficus concinna seedlings grown under high-temperature
      (HT) stress for 48 h. Our results showed that the activities of ascorbate
      peroxidase (APX), superoxide dismutase (SOD), glutathione S-transferase (GST),
      glutathione peroxidase (GPX) and glyoxalase II (Gly II) were increased under two
      levels of HT stress. Compared with control the activities of catalase (CAT) and
      dehydroascorbate reductase (DHAR) were not changed due to HT stress. The
      activities of glutathione reductase (GR), monodehydroascorbate reductase (MDHAR)
      and glyoxalase I (Gly I) were increased only at moderate HT stress. Despite these
      protective mechanisms, HT stress induced oxidative stress in F. concinna
      seedlings, as indicated by the increased levels of ROS, malondialdehyde (MDA) and
      MG, and the reductions in chlorophyll levels and relative water content. The
      contents of reduced glutathione (GSH) and ascorbate (AsA) were not changed under
      moderate HT stress. Spraying with 24-epibrassinolide (EBR) alone had little
      influence on the non-enzymatic antioxidants and the activities of antioxidant
      enzymes. However, EBR pretreatment under HT stress resulted in an increase in GSH
      and AsA content, maintenance of high redox state of GSH and AsA, and enhanced ROS
      and MG detoxification by further elevating the activities of SOD, GST, GPX, APX,
      MDHAR, GR, DHAR, Gly I and Gly II, as evident by lower level of ROS, MDA and MG.
      It may be concluded that EBR could alleviate the HT-induced oxidative stress by
      increasing the enzymatic and non-enzymatic antioxidant defence, and glyoxalase
      systems in F. concinna seedlings. 

PMID- 25609564
TI  - Contrast-enhanced [18 F] fluorodeoxyglucose-positron emission tomography/computed
      tomography in clinical oncology: tumor-, site-, and question-based comparison
      with standard positron emission tomography/computed tomography.
AB  - BACKGROUND: The present study aimed to evaluate the added value of contrast
      enhanced computed tomography (ceCT) in comparison to standard, non-enhanced CT in
      the context of a combined positron emission tomography (PET)/CT examination by
      means of a tumor-, site-, and clinical question-based approach. METHODS: Analysis
      was performed in 202 patients undergoing PET/CT consisting of a multiphase CT
      protocol followed by a whole-body PET. The Cochran Q test was performed, followed
      by a multiple comparisons correction (McNemar test and Bonferroni adjustment), to
      compare standard and contrast-enhanced PET (cePET/CT). Histopathology or clinical
      radiologic follow-up greater than 1 year was used as a reference. RESULTS:
      cePET/CT showed significantly different results with respect to standard PET/CT
      in head and neck and gastrointestinal cancer (P = 0.02 and 0.0002, respectively),
      in the evaluation of lesions located in the abdomen (P = 0.009), and in the
      context of disease restaging (P = 0.003). In all these clinical scenarios, adding
      ceCT resulted in a distinct benefit, by yielding a higher percentage of change in
      patient management. CONCLUSION: These data strongly underline the importance of
      strictly selecting patients for the combined exam. In particular, patient
      selection should not be driven solely by mere tumor classification, but should
      also account for the clinical question and the anatomical location of the
      neoplastic disease, which can significantly impact patient management.

PMID- 25609565
TI  - Silicon-nanowire based attachment of silicon chips for mouse embryo labelling.
AB  - The adhesion of small silicon chips to cells has many potential applications as
      direct interconnection of the cells to the external world can be accomplished.
      Hence, although some typical applications of silicon nanowires integrated into
      microsystems are focused on achieving a cell-on-a-chip strategy, we are
      interested in obtaining chip-on-a-cell systems. This paper reports the design,
      technological development and characterization of polysilicon barcodes featuring
      silicon nanowires as nanoscale attachment to identify and track living mouse
      embryos during their in vitro development. The chips are attached to the outer
      surface of the Zona Pellucida, the cover that surrounds oocytes and embryos, to
      avoid the direct contact between the chip and the embryo cell membrane. Two
      attachment methodologies, rolling and pushpin, which allow two entirely different
      levels of applied forces to attach the chips to living embryos, are evaluated.
      The former consists of rolling the mouse embryos over one barcode with the
      silicon nanowires facing upwards, while in the latter, the barcode is pushed
      against the embryo with a micropipette. The effect on in vitro embryo development
      and the retention rate related to the calculated applied forces are stated. Field
      emission scanning electron microscopy inspection, which allowed high-resolution
      imaging, also confirms the physical attachment of the nanowires with some of them
      piercing or wrapped by the Zona Pellucida and revealed extraordinary bent silicon
      nanowires. 

PMID- 25609566
TI  - An integrated phylogenomic approach toward pinpointing the origin of
      mitochondria.
AB  - Overwhelming evidence supports the endosymbiosis theory that mitochondria
      originated once from the Alphaproteobacteria. However, its exact position in the
      tree of life remains highly debated. This is because systematic errors, including
      biased taxonomic sampling, high evolutionary rates and sequence composition bias
      have long plagued the mitochondrial phylogenetics. In this study, we address this
      issue by 1) increasing the taxonomic representation of alphaproteobacterial
      genomes by sequencing 18 phylogenetically novel species. They include 5
      Rickettsiales and 4 Rhodospirillales, two orders that have shown close
      affiliations with mitochondria previously, 2) using a set of 29 slowly evolving
      mitochondria-derived nuclear genes that are less biased than mitochondria-encoded
      genes as the alternative "well behaved" markers for phylogenetic analysis, 3)
      applying site heterogeneous mixture models that account for the sequence
      composition bias. With the integrated phylogenomic approach, we are able to for
      the first time place mitochondria unequivocally within the Rickettsiales order,
      as a sister clade to the Rickettsiaceae and Anaplasmataceae families, all
      subtended by the Holosporaceae family. Our results suggest that mitochondria most
      likely originated from a Rickettsiales endosymbiont already residing in the host,
      but not from the distantly related free-living Pelagibacter and Rhodospirillales.

PMID- 25609567
TI  - Engineering an in vitro air-blood barrier by 3D bioprinting.
AB  - Intensive efforts in recent years to develop and commercialize in vitro
      alternatives in the field of risk assessment have yielded new promising two- and
      three dimensional (3D) cell culture models. Nevertheless, a realistic 3D in vitro
      alveolar model is not available yet. Here we report on the biofabrication of the
      human air-blood tissue barrier analogue composed of an endothelial cell, basement
      membrane and epithelial cell layer by using a bioprinting technology. In contrary
      to the manual method, we demonstrate that this technique enables automatized and
      reproducible creation of thinner and more homogeneous cell layers, which is
      required for an optimal air-blood tissue barrier. This bioprinting platform will
      offer an excellent tool to engineer an advanced 3D lung model for high-throughput
      screening for safety assessment and drug efficacy testing. 

PMID- 25609568
TI  - Optimizing the uptake of health checks for people with intellectual disabilities.
AB  - The provision of an annual health check for adult persons with an intellectual
      disability is intended to counter the health inequalities experienced by this
      population. This study documents the uptake of checks across general practitioner
      (GP) practices in Northern Ireland over a 3-year period. In all, 84% of GP
      practices provided health checks covering an estimated 87% of the population with
      intellectual (learning) disabilities. Overall 64% of people known to practices
      had received a health check which is significantly higher than comparable
      percentages of around 46% reported for England. Nevertheless the uptake by
      patients varied across the five trusts in Northern Ireland but less so than
      across the English health authorities. These variations were linked to the
      deployment of health facilitators. However, younger people living with families,
      or independently, in more socially deprived areas were less likely to have had a
      health check. Ongoing monitoring is needed to ensure the quality of the checks
      provided and that health improvement plans are implemented. 

PMID- 25609569
TI  - Novel agents have a significant impact on survival of patients with multiple
      myeloma.
AB  - BACKGROUND: In addition to conventional chemotherapeutic regimens and autologous
      transplantation, novel agents are now part of the treatment armamentarium against
      multiple myeloma (MM). To evaluate the presumed benefit of novel agents, we
      performed an analysis of patients with MM at our institution before and after the
      availability of novel agents. DESIGN AND METHODS: In all, 200 consecutive
      patients with newly diagnosed MM (male = 119; female = 81; median age: 61.5
      years) treated at our institution between June 1993 and December 2008 were
      included in this retrospective analysis. Patient cohorts were defined according
      to date of diagnosis (before and after 01-Jan-2000, respectively), treatment
      received (chemotherapy only vs. therapy including novel agents), risk profile
      (International Staging System (ISS)-stage), and cytogenetic features. Primary
      focus of the analysis was overall survival (OS). RESULTS: Median OS for MM
      patients who received conventional chemotherapy was 45.2 months and for patients
      who received novel agents 74.6 months (P < 0.01). OS for those patients who
      relapsed after autotransplantation before 2000 was 35.2 months, but 72.7 months
      (P < 0.01) for those patients with a later relapse. Prolongation of survival for
      patients receiving novel agents was most evident for patients with ISS stage III
      (median OS 68.4 vs. 11.2 months for patients with chemotherapy only; P < 0.01).
      MM patients with an intermediate risk had a longer median OS when receiving novel
      agents (47.2 vs. 32.8 months). CONCLUSION: Treatment with novel agents in MM
      resulted in a significant prolongation of OS. Benefit of therapy with novel
      agents was particularly evident for transplant-eligible patients and MM patients
      with unfavorable prognosis.

PMID- 25609570
TI  - Compound signature detection on LINCS L1000 big data.
AB  - The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big
      data provide gene expression profiles induced by over 10 000 compounds, shRNAs,
      and kinase inhibitors using the L1000 platform. We developed csNMF, a systematic
      compound signature discovery pipeline covering from raw L1000 data processing to
      drug screening and mechanism generation. The csNMF pipeline demonstrated better
      performance than the original L1000 pipeline. The discovered compound signatures
      of breast cancer were consistent with the LINCS KINOMEscan data and were
      clinically relevant. The csNMF pipeline provided a novel and complete tool to
      expedite signature-based drug discovery leveraging the LINCS L1000 resources. 

PMID- 25609571
TI  - Perioperative anticoagulation management in antiphospholipid syndrome.
AB  - Patients with antiphospholipid syndrome are at increased risk of developing
      thrombotic and hemorrhagic complications after cardiac surgery, and may have
      abnormal coagulation tests and develop thrombocytopenia after invasive
      procedures, which can complicate the perioperative management of anticoagulant
      therapy. We describe a patient with chronic thromboembolic pulmonary hypertension
      and antiphospholipid syndrome, who presented with prolonged activated partial
      thromboplastin and activated clotting times, and developed thrombocytopenia after
      the catheterization workup. We performed pulmonary endarterectomy and
      successfully managed anticoagulation by restricting heparin use at the time of
      surgery and monitoring the heparin effect by measuring heparin concentrations
      during cardiopulmonary bypass. 

PMID- 25609574
TI  - Semiconductor to metal transition in bilayer phosphorene under normal compressive
      strain.
AB  - Phosphorene, a two-dimensional analog of black phosphorous, has been a subject of
      immense interest recently, due to its high carrier mobilities and a tunable
      bandgap. So far, tunability has been predicted to be obtained with very high
      compressive/tensile in-plane strains, and vertical electric field, which are
      difficult to achieve experimentally. Here, we show using density functional
      theory based calculations the possibility of tuning electronic properties by
      applying normal compressive strain in bilayer phosphorene. A complete and fully
      reversible semiconductor to metal transition has been observed at [Formula: see
      text] strain, which can be easily realized experimentally. Furthermore, a direct
      to indirect bandgap transition has also been observed at [Formula: see text]
      strain, which is a signature of unique band-gap modulation pattern in this
      material. The absence of negative frequencies in phonon spectra as a function of
      strain demonstrates the structural integrity of the sheets at relatively higher
      strain range. The carrier mobilities and effective masses also do not change
      significantly as a function of strain, keeping the transport properties nearly
      unchanged. This inherent ease of tunability of electronic properties without
      affecting the excellent transport properties of phosphorene sheets is expected to
      pave way for further fundamental research leading to phosphorene-based multi
      physics devices. 

PMID- 25609572
TI  - Break-seq reveals hydroxyurea-induced chromosome fragility as a result of
      unscheduled conflict between DNA replication and transcription.
AB  - We have previously demonstrated that in Saccharomyces cerevisiae replication,
      checkpoint inactivation via a mec1 mutation leads to chromosome breakage at
      replication forks initiated from virtually all origins after transient exposure
      to hydroxyurea (HU), an inhibitor of ribonucleotide reductase. Here we sought to
      determine whether all replication forks containing single-stranded DNA gaps have
      equal probability of producing double-strand breaks (DSBs) when cells attempt to
      recover from HU exposure. We devised a new methodology, Break-seq, that combines
      our previously described DSB labeling with next generation sequencing to map
      chromosome breaks with improved sensitivity and resolution. We show that DSBs
      preferentially occur at genes transcriptionally induced by HU. Notably, different
      subsets of the HU-induced genes produced DSBs in MEC1 and mec1 cells as
      replication forks traversed a greater distance in MEC1 cells than in mec1 cells
      during recovery from HU. Specifically, while MEC1 cells exhibited chromosome
      breakage at stress-response transcription factors, mec1 cells predominantly
      suffered chromosome breakage at transporter genes, many of which are the
      substrates of those transcription factors. We propose that HU-induced chromosome
      fragility arises at higher frequency near HU-induced genes as a result of
      destabilized replication forks encountering transcription factor binding and/or
      the act of transcription. We further propose that replication inhibitors can
      induce unscheduled encounters between replication and transcription and give rise
      to distinct patterns of chromosome fragile sites. 

PMID- 25609573
TI  - Soft tissue interposition is effective for protecting the neourethra during
      hypospadias surgery and preventing postoperative urethrocutaneous fistula: a
      single surgeon's experience of 243 cases.
AB  - PURPOSE: Soft tissue interposition (STI) during hypospadias repair (HR)
      purportedly prevents postoperative urethrocutaneous fistula (PUF) by supporting
      the neourethra. We report our experience. METHODS: Data from 243 hypospadias
      patients treated by a single surgeon from 1997 to 2014 by urethroplasty (UP) with
      STI (n = 229; UP + STI) and UP without STI (n = 14; UP-STI) were collated
      prospectively and compared for incidence of PUF. Re-operative UP were excluded.
      RESULTS: Hypospadias was distal (n = 55), mid-shaft (n = 59),
      proximal/penoscrotal (n = 109), scrotal (n = 15), and perineal (n = 5). UP was
      single-staged in 86, multi-staged in 157; mean age at UP was 3.1 +/- 2.4 years.
      Soft tissue used for STI was prepucial inner dartos fascia (inner dartos: n =
      88), ventral dartos fascia (ventral dartos: n = 15), pedicled external spermatic
      fascia (ESF: n = 84), adipose tissue surrounding the spermatic cord (pericordal:
      n = 9), scrotal adipose tissue (n = 8), or a combination of tissues (combined: n
      = 25). Mean follow-up was 6.4 +/- 4.6 (range 0.6-16.8) years. Overall incidence
      of PUF was 10/243 (4.1 %); 7/229 (3.1 %) for UP + STI and 3/14 (21.4 %) in UP-STI
      (p < 0.05); incidence versus type of hypospadias was 1/55 for distal (1.8 %),
      3/59 for mid-shaft (5.1 %), 5/109 for proximal/penoscrotal (4.6 %), 0/15 for
      scrotal (0 %), and 1/5 for perineal (20 %); incidence versus type of STI was 7/88
      for inner dartos, 0/15 for ventral dartos, 0/84 for ESF, 0/9 for pericordal
      adipose tissue, 0/8 for scrotal adipose tissue, and 0/25 for combined. All PUF
      were repaired successfully. Satisfaction with penile cosmesis was acceptable
      (10.3 %) or good (89.7 %) without any testicular complications or scrotal
      deformity. CONCLUSION: STI, especially ESF, would appear to effectively prevent
      PUF in HR.

PMID- 25609575
TI  - A single blood test to rule out myocardial infarction?

PMID- 25609576
TI  - How unique is pure erythroid leukaemia? A retrospective analysis of seven cases
      and review of the literature.
AB  - AIMS: Pure erythroid leukaemia (PEL) is a rare subtype of acute myeloid leukaemia
      (AML) and its clinicopathological features are not well-defined. The aim of this
      study was to describe the immunophenotypic, cytogenetic and clinical features of
      PEL and to compare these with cases of AML with >= 50% erythroblasts. METHODS:
      Cases of PEL according to WHO morphological criteria diagnosed at three
      institutions from 1997 to 2013 were included. A comparison cohort comprised of
      AML with >= 50% erythroblasts. The clinical, histopathology, immunophenotypic and
      cytogenetic features of cases were analysed. We also reviewed the existing
      literature on PEL, and combined our cohort with previously reported cases of PEL
      in a pooled analysis. RESULTS: There were seven cases of PEL diagnosed at our
      institutions. There was a high incidence of either prior chemoradiotherapy
      exposure or evolution from pre-existing myelodysplastic syndrome (MDS) (71%). The
      leukaemic blasts frequently expressed glycophorin C (100%), CD117 (83%) and were
      myeloperoxidase negative (83%). Complex karyotypes were present in 83% of cases.
      Median overall survival was 2.9 months. Compared with AML with >= 50%
      erythroblasts, cases of PEL demonstrated a higher incidence of adverse-risk
      cytogenetics (p=0.01) and prior exposure to chemoradiotherapy (p=0.01).
      CONCLUSIONS: PEL appears to be a unique entity that is often secondary or therapy
      related, commonly features a complex karyotype and has a poor prognosis. It is
      morphologically and immunophenotypically distinct from other cases of AML with
      erythroid hyperplasia.

PMID- 25609577
TI  - KRAS mutant allele-specific imbalance (MASI) assessment in routine samples of
      patients with metastatic colorectal cancer.
AB  - AIMS: Patients with colorectal cancer harbouring KRAS mutations do not respond to
      antiepidermal growth factor receptor (anti-EGFR) therapy. Community screening for
      KRAS mutation selects patients for treatment. When a KRAS mutation is identified
      by direct sequencing, mutant and wild type alleles are seen on the sequencing
      electropherograms. KRAS mutant allele-specific imbalance (MASI) occurs when the
      mutant allele peak is higher than the wild type one. The aims of this study were
      to verify the rate and tissue distribution of KRAS MASI as well as its clinical
      relevance. METHODS: A total of 437 sequencing electropherograms showing KRAS exon
      2 mutation was reviewed and in 30 cases next generation sequencing (NGS) was also
      carried out. Five primary tumours were extensively laser capture microdissected
      to investigated KRAS MASI tissue spatial distribution. KRAS MASI influence on the
      overall survival was evaluated in 58 patients. In vitro response to anti-EGFR
      therapy in relation to different G13D KRAS MASI status was also evaluated.
      RESULTS: On the overall, KRAS MASI occurred in 58/436 cases (12.8%), being more
      frequently associated with G13D mutation (p=0.05) and having a heterogeneous
      tissue distribution. KRAS MASI detection by Sanger Sequencing and NGS showed 94%
      (28/30) concordance. The longer overall survival of KRAS MASI negative patients
      did not reach statistical significance (p=0.08). In cell line model G13D KRAS
      MASI conferred resistance to cetuximab treatment. CONCLUSIONS: KRAS MASI is a
      significant event in colorectal cancer, specifically associated with G13D
      mutation, and featuring a heterogeneous spatial distribution, that may have a
      role to predict the response to EGFR inhibitors. The foreseen implementation of
      NGS in community KRAS testing may help to define KRAS MASI prognostic and
      predictive significance.

PMID- 25609578
TI  - Illness perceptions, negative emotions, and pain in patients with noncardiac
      chest pain.
AB  - Illness-specific cognitions are associated with outcomes in numerous health
      conditions, however, little is known about their role in noncardiac chest pain
      (NCCP). NCCP is prevalent, impairing, and associated with elevated health care
      utilization. Our objective was to investigate the relations between illness
      perceptions, emotion, and pain in a sample of 196 adult patients diagnosed with
      NCCP. We found that negative illness perceptions were associated with greater
      anxiety, depression, chest pain, and pain-related life interference while
      controlling for the effects of demographic and pain-related variables. These
      results expand current NCCP theory and may inform future treatment development. 

PMID- 25609579
TI  - [Modern imaging of liver metastases].
AB  - CLINICAL/METHODICAL ISSUE: The liver is the second most common location of
      metastases following the lymph nodes. The accurate characterization of focal
      liver lesions in oncology patients is especially important because of the high
      prevalence of benign liver lesions and the possibility of co-existing benign and
      malignant lesions. The exact interpretation of these lesions is crucial for
      therapeutic decisions and thus for the prognosis of the patient. STANDARD
      RADIOLOGICAL METHODS: It is essential to detect all focal liver lesions and to
      distinguish benign from malignant lesions, especially in the management of
      oncology patients. Numerous imaging modalities are available for these challenges
      in the daily routine. An extensive understanding of the advantages and
      limitations of the various imaging modalities and knowledge of the morphology and
      the typical and atypical appearances of the different metastases is important.
      METHODICAL INNOVATIONS: This review explains the radiological criteria for
      various metastases in different modalities. To evaluate the individual prognosis
      and risk assessment preoperatively, functional imaging is necessary. These
      personalized pretherapeutic diagnostics are discussed.

PMID- 25609580
TI  - [Targeted radiological therapy of liver tumors].
AB  - BACKGROUND: Interventional radiology offers a variety of treatment options for
      liver tumors. Depending on the tumor entity and the extent of the disease,
      patients can be treated with a curative or palliative intent. In order to make a
      decision on the best course of treatment for the individual patient, knowledge
      about the possible therapies and their limitations is essential. OBJECTIVES: The
      aim of this article is a structured listing of targeted radiological therapies
      for the treatment of liver tumors and an overview of the specific technical
      aspects and possible limitations. MATERIALS AND METHODS: This study involved a
      selective literature search as well as personal experiences in interventional
      radiological treatment of liver tumors. CONCLUSION: The wide range of available
      therapies requires an individual assessment of each patient taking the achievable
      results into account. The decision for an interventional radiological therapy
      should be made in an interdisciplinary tumor board.

PMID- 25609581
TI  - [Digital breast tomosynthesis].
AB  - In digital breast tomosynthesis several low dose mammograms are acquired from
      different angles to calculate thin slices of synthetic mammograms from
      algorithms. Similar to computed tomography and magnetic resonance imaging, breast
      tomosynthesis provides breast images which are virtually free from
      superimposition. This is in particular important in cases of high mammographic
      density to differentiate real masses and architectural distortions from the
      overlying parenchyma. In comparison to full field digital mammography
      tomosynthesis can improve the cancer detection rate and reduce the recall rate.
      The limitations of tomosynthesis are the higher radiation dose and the longer
      reporting time compared to full field digital mammography. Until the radiation
      dose can be significantly reduced it is advisable to use tomosynthesis in
      addition to full field digital mammography primarily for the assessment of
      suspicious mammographic findings and not for breast cancer screening. 

PMID- 25609582
TI  - Comparison of left ventricular systolic function and mechanical dyssynchrony
      using equilibrium radionuclide angiography in patients with right ventricular
      outflow tract versus right ventricular apical pacing: A prospective single-center
      study.
AB  - BACKGROUND: Chronic ventricular pacing is known to adversely affect left
      ventricular (LV) function. Studies comparing right ventricular outflow tract
      (RVOT) pacing with RV apical (RVA) pacing have shown heterogeneous outcomes. Our
      aim was to objectively assess LV function and mechanical dyssynchrony in patients
      with RVOT and RVA pacing using equilibrium radionuclide angiography (ERNA).
      METHODS: Fifty-one patients who underwent permanent pacemaker implantation and
      had normal LV function were prospectively included. Twenty-nine patients had
      pacemaker lead implanted in the RVOT and 22 at the RVA site. All patients
      underwent ERNA within 5 days post-pacemaker implantation and follow-up studies at
      6 and 12 months. Standard deviation of LV mean phase angle (SD LV mPA) expressed
      in degrees, which was derived by Fourier first harmonic analysis of phase images,
      was used to quantify left intraventricular dyssynchrony. RESULTS: No significant
      difference was observed between the two groups with respect to indication (P =
      .894), Type/mode (P = .985), and percentage of ventricular pacing (P = .352).
      Paced QRS duration was significantly longer in RVA group than RVOT group (P =
      .05). There was no statistically significant difference between the RVA and RVOT
      groups at baseline with respect to LVEF (P = .596) and SD LV mPA (P = .327).
      Within the RVA group, a significant decline in LVEF was observed over 12-month
      follow-up (from 57.3% +/- 5.32% to 55.6% +/- 6.25%; P = .012). In the RVOT group,
      the change in LVEF was not statistically significant (from 56.7% +/- 4.08% to
      54.3% +/- 6.63%; P = .159). No significant change in SD LV mPA was observed over
      12-month follow-up within the RVA group (from 10.5 +/- 2.58 degrees  to 10.4 +/-
      3.54 degrees ; P = 1.000) as well as in the RVOT group (from 9.7 +/- 3.28 degrees
      to 9.4 +/- 2.85 degrees ; P = .769). However, between the RVA and RVOT groups,
      no significant difference was observed at 12-month follow-up in terms of LVEF and
      dyssynchrony (LVEF P = .488; SD LV mPA P = .296). CONCLUSION: No significant
      difference was observed between RVOT and RVA groups with regard to LV function
      and synchrony over a 12-month follow-up. RVOT pacing offers may lead to better
      preservation of LV function on longer follow-up.

PMID- 25609584
TI  - Analysis of genome-wide RNA-sequencing data suggests age of the CEPH/Utah (CEU)
      lymphoblastoid cell lines systematically biases gene expression profiles.
AB  - In human, Lymphoblastoid cell lines (LCLs) from the CEPH/CEU (Centre d'Etude du
      Polymorphisme Humain - Utah) family resource have been extensively used for
      examining the genetics of gene expression levels. However, we noted that CEU/CEPH
      cell lines were collected and transformed approximately thirty years ago, much
      earlier than the other cell lines from the pertaining individuals, which we
      suspected could potentially affect gene expression, data analysis and results
      interpretation. In this study, by analyzing RNA sequencing data of CEU and the
      other three European populations as well as an African population, we
      systematically examined and evaluated the potential confounding effect of LCL age
      on gene expression levels and patterns. Our results indicated that gene
      expression profiles of CEU samples have been biased by the older age of CEU cell
      lines. Interestingly, most of CEU-specific expressions are associated with
      functions related to cell proliferation, which are more likely due to older age
      of cell lines than intrinsic characters of the population. We suggested the
      results be carefully explained when CEU LCLs are used for transcriptomic data
      analysis in future studies. 

PMID- 25609585
TI  - The epigenetic modifier EZH2 controls melanoma growth and metastasis through
      silencing of distinct tumour suppressors.
AB  - Increased activity of the epigenetic modifier EZH2 has been associated with
      different cancers. However, evidence for a functional role of EZH2 in
      tumorigenesis in vivo remains poor, in particular in metastasizing solid cancers.
      Here we reveal central roles of EZH2 in promoting growth and metastasis of
      cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much
      as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease
      through inhibition of growth and virtually abolishes metastases formation without
      affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2
      inactivation impairs proliferation and invasiveness, accompanied by re-expression
      of tumour suppressors connected to increased patient survival. These EZH2 target
      genes suppress either melanoma growth or metastasis in vivo, revealing the dual
      function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic
      repression is highly relevant especially during advanced melanoma progression,
      which makes EZH2 a promising target for novel melanoma therapies. 

PMID- 25609586
TI  - Unexplained high BMD in DXA-scanned patients is generalized throughout the
      skeleton and characterized by thicker cortical and trabecular bone.
AB  - Unexplained high bone mineral density (BMD) is a rare condition and the
      mechanisms responsible are yet to be described in detail. The aim of the study
      was to identify patients with unexplained high BMD from a local DXA database and
      compare their radiological phenotype with an age- and a gender-matched group of
      population-based controls. We defined high BMD as a DXA Z-score >= + 2.5 at the
      total hip and lumbar spine. We characterized the findings as "unexplained" if no
      osteodegenerative changes, bone metabolic disease, or arthritis at the hip or
      lumbar spine was observed. All participants were investigated with high
      resolution peripheral quantitative computed tomography (HR-pQCT), QCT, DXA,
      fasting blood samples, a 24-h urine sample, and questionnaires. The DXA database
      contained data on 25,118 patients. Initially, 138 (0.55%) potential participants
      with high BMD were identified, and during the study ten additional cases were
      identified from new DXA scans. Sixty-seven patients accepted to participate in
      the study, and among these we identified 15 women and one man with unexplained
      high BMD. These 15 women had higher BMD throughout the skeleton relative to
      controls, similar area/volume at the hip and the distal extremities, a higher
      number of trabeculae, which was thicker than in the controls, and a higher finite
      element estimated bone strength. The 15 women were heavier and had a higher fat
      mass then controls. We conclude that patients with unexplained high BMD have a
      generalized high BMD phenotype throughout their skeleton, which is characterized
      with a denser microarchitecture.

PMID- 25609587
TI  - Pathological aspects of bovine focal fibrogranulomatous proliferative
      panniculitis (Lechiguana).
AB  - Lechiguana is a disease of cattle caused by an interaction between Dermatobia
      hominis warble and the bacteria Manheimia granulomatis. It is characterized by
      subcutaneous swellings that grow rapidly and result in death after 3 to 8 months.
      The objective of this paper was to investigate some vascular and fibrogenic
      changes of the disease at different lesion stages by histochemical and
      immunohistochemical techniques. A peculiar histopathological aspect observed
      during a proliferative phase (before treatment) was the intense vasculitis,
      described as degenerative and fibro-proliferative, expressed by the oncogene p53,
      possibly caused by the presence of bacteria in close contact with enthotelial
      cells, along with dense accumulations of lymphoid cells around venules. The
      synthesis of collagen fibers during the development of Lechiguana lesions assume
      a structural aspect of star arrangement with fiber radiation centers that
      gradually interconnect to design the Extracellular Matrix (ECM) framework, seen
      by Confocal Laser Scanning Microscopy (CSLM). Angiogenesis was the most
      characteristic finding in both proliferative and regressive stages as seen by the
      immunohistochemical expression of cytoskeleton proteins and von Willebrand
      (Factor VIII-Related Antigen). Additionally, in all tissues samples, active ECM
      elements like Metalloproteinases (MMPs), Tissue Inhibitors Metalloproteinases
      (TIMP) and Fibronectin (FN) were mainly associated to vessels structures. The
      extraordinary regression of exuberant granulation tissue after treatment is
      undoubtedly associated to the maintenance of the vascular components observed
      during the regressive phase.

PMID- 25609588
TI  - Selective CO2 gas adsorption in the narrow crystalline cavities of flexible
      peptide metallo-macrocycles.
AB  - Crystalline peptide Ni(ii)-macrocycles (BF4(-) salt) exhibited moderate CO2 gas
      adsorption (ca. 6-7 CO2 molecules per macrocycle) into very narrow cavities
      (narrowest part <2 A), accompanied by the expansion of the cavities. The BF4(-)
      salt demonstrated selective uptake of CO2 gas in preference to CH4 and N2 gases. 

PMID- 25609589
TI  - Preschool-onset depression predicts major depressive disorder and other
      psychiatric disorders in later childhood and early adolescence.

PMID- 25609590
TI  - Negative effect of alcohol use on mood among people with psychosis.

PMID- 25609591
TI  - Re: staying on target-reply to comments by Loyal et al.

PMID- 25609592
TI  - European consensus meeting of ARM-Net members concerning diagnosis and early
      management of newborns with anorectal malformations.
AB  - The ARM-Net (anorectal malformation network) consortium held a consensus meeting
      in which the classification of ARM and preoperative workup were evaluated with
      the aim of improving monitoring of treatment and outcome. The Krickenbeck
      classification of ARM and preoperative workup suggested by Levitt and Pena, used
      as a template, were discussed, and a collaborative consensus was achieved. The
      Krickenbeck classification is appropriate in describing ARM for clinical use. The
      preoperative workup was slightly modified. In males with a visible fistula, no
      cross-table lateral X-ray is needed and an anoplasty or (mini-) posterior
      sagittal anorectoplasty can directly be performed. In females with a small
      vestibular fistula (Hegar size <5 mm), a primary repair or colostomy is
      recommended; the repair may be delayed if the fistula admits a Hegar size >5 mm,
      and in the meantime, gentle painless dilatations can be performed. In both male
      and female perineal fistula and either a low birth weight (<2,000 g) or severe
      associated congenital anomalies, prolonged preoperative painless dilatations
      might be indicated to decrease perioperative morbidity caused by general
      anesthesia. The Krickenbeck classification is appropriate in describing ARM for
      clinical use. Some minor modifications to the preoperative workup by Levitt and
      Pena have been introduced in order to refine terminology and establish a
      comprehensive preoperative workup.

PMID- 25609593
TI  - B-type natriuretic peptide as a predictor of ischemia/reperfusion injury
      immediately after myocardial reperfusion in patients with ST-segment elevation
      acute myocardial infarction.
AB  - BACKGROUND: In animal models of acute myocardial infarction (AMI), B-type
      natriuretic peptide (BNP) administered before and during coronary occlusion
      limits infarct size. However, the relation between plasma BNP levels and
      ischemia/reperfusion injury remains unclear. METHODS: 302 patients with ST
      segment elevation AMI (STEMI) received emergency percutaneous coronary
      intervention within six hours from the onset. The patients were divided into two
      groups according to the plasma BNP level before angiography: group L (n=151), BNP
      <= 32.2 pg/ml; group H (n=151), BNP >32.2 pg/ml. The Selvester QRS-scoring system
      was used to estimate infarct size. RESULTS: The rate of ischemia/reperfusion
      injury immediately after reperfusion, defined as reperfusion ventricular
      arrhythmias (26% vs. 11%, p=0.001) and ST-segment re-elevation (44% vs. 22%,
      p=0.008), was higher in group L than in group H. Group L had a greater increase
      in the QRS score during percutaneous coronary intervention (3.55 +/- 0.17 vs.
      2.09 +/- 0.17, p<0.001) and a higher QRS score 1 h after percutaneous coronary
      intervention (5.77 +/- 0.28 vs. 4.51 +/- 0.28, p=0.002). On multivariate
      analysis, plasma BNP levels in the lower 50th percentile were an independent
      predictor of reperfusion injury (odds ratio, 2.620; p<0.001). The odds ratios of
      reperfusion injury according to decreasing quartiles of BNP level, as compared
      with the highest quartile, were 1.536, 3.692 and 4.964, respectively (p
      trend=0.002). CONCLUSIONS: Plasma BNP level before percutaneous coronary
      intervention may be a predictor of ischemia/reperfusion injury and the resultant
      extent of myocardial damage. Our findings suggest that high plasma BNP levels
      might have a clinically important protective effect on ischemic myocardium in
      patients with STEMI who receive percutaneous coronary intervention.

PMID- 25609594
TI  - Ethanol exposure induces neonatal neurodegeneration by enhancing CB1R Exon1
      histone H4K8 acetylation and up-regulating CB1R function causing neurobehavioral
      abnormalities in adult mice.
AB  - BACKGROUND: Ethanol exposure to rodents during postnatal day 7 (P7), which is
      comparable to the third trimester of human pregnancy, induces long-term
      potentiation and memory deficits. However, the molecular mechanisms underlying
      these deficits are still poorly understood. METHODS: In the present study, we
      explored the potential role of epigenetic changes at cannabinoid type 1 (CB1R)
      exon1 and additional CB1R functions, which could promote memory deficits in
      animal models of fetal alcohol spectrum disorder. RESULTS: We found that ethanol
      treatment of P7 mice enhances acetylation of H4 on lysine 8 (H4K8ace) at CB1R
      exon1, CB1R binding as well as the CB1R agonist-stimulated GTPgammaS binding in
      the hippocampus and neocortex, two brain regions that are vulnerable to ethanol
      at P7 and are important for memory formation and storage, respectively. We also
      found that ethanol inhibits cyclic adenosine monophosphate response element
      binding protein (CREB) phosphorylation and activity-regulated cytoskeleton
      associated protein (Arc) expression in neonatal and adult mice. The blockade or
      genetic deletion of CB1Rs prior to ethanol treatment at P7 rescued CREB
      phosphorylation and Arc expression. CB1R knockout mice exhibited neither ethanol
      induced neurodegeneration nor inhibition of CREB phosphorylation or Arc
      expression. However, both neonatal and adult mice did exhibit enhanced CREB
      phosphorylation and Arc protein expression. P7 ethanol-treated adult mice
      exhibited impaired spatial and social recognition memory, which were prevented by
      the pharmacological blockade or deletion of CB1Rs at P7. CONCLUSIONS: Together,
      these findings suggest that P7 ethanol treatment induces CB1R expression through
      epigenetic modification of the CB1R gene, and that the enhanced CB1R function
      induces pCREB, Arc, spatial, and social memory deficits in adult mice.

PMID- 25609595
TI  - Quantification of central substance P receptor occupancy by aprepitant using
      small animal positron emission tomography.
AB  - BACKGROUND: Central substance P receptors, termed NK-1 receptors, have been
      considered as therapeutic targets in the development of drugs against diverse
      conditions, including emesis, overactive bladder, and depression. METHODS: Here,
      we applied small animal positron emission tomography (PET) and a radioligand for
      NK-1 receptors ([(18)F]FE-SPA-RQ) for measuring occupancies of these receptors by
      a selective antagonist (aprepitant) in order to examine the validity of this in
      vivo imaging system for preclinical characterization of candidate agents acting
      on NK-1 receptors, and as a tool for predicting optimal doses in humans. RESULTS:
      PET in gerbils depicted high uptake in the striatum and dose-dependent
      displacement with increasing doses of aprepitant. Occupancies increased as a
      function of aprepitant plasma concentrations according to a one-site competition
      model, which agrees with reported occupancy-concentration relationships in
      clinical studies after correction for species differences in plasma protein
      unbound aprepitant fractions. These occupancy data were further supported by ex
      vivo autoradiography of brain samples from aprepitant-treated gerbils. In a pilot
      study of a marmoset, we obtained more accurate determinations of NK-1 receptor
      occupancy, less affected by spillover of signals from extracranial tissues than
      in gerbil experiments. CONCLUSIONS: These findings support the utility of small
      animals and quantitative PET in the development of drugs targeting NK-1
      receptors.

PMID- 25609596
TI  - GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and
      CREB/BDNF down-regulation in the hippocampus.
AB  - BACKGROUND: Zinc may act as a neurotransmitter in the central nervous system by
      activation of the GPR39 metabotropic receptors. METHODS: In the present study, we
      investigated whether GPR39 knockout would cause depressive-like and/or anxiety
      like behavior, as measured by the forced swim test, tail suspension test, and
      light/dark test. We also investigated whether lack of GPR39 would change levels
      of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor
      (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and
      frontal cortex of GPR39 knockout mice subjected to the forced swim test, as
      measured by Western-blot analysis. RESULTS: In this study, GPR39 knockout mice
      showed an increased immobility time in both the forced swim test and tail
      suspension test, indicating depressive-like behavior and displayed anxiety-like
      phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus,
      but not in the frontal cortex, which indicates region specificity for the
      impaired CREB/BDNF pathway (which is important in antidepressant response) in the
      absence of GPR39. There were no changes in TrkB protein in either structure. In
      the present study, we also investigated activity in the hypothalamus-pituitary
      adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice
      had higher serum corticosterone levels and lower glucocorticoid receptor levels
      in the hippocampus and frontal cortex. CONCLUSIONS: There were no changes in the
      GPR39 knockout mice in comparison with the wild-type control mice, which does not
      support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The
      results of this study indicate the involvement of the GPR39 Zn(2+)-sensing
      receptor in the pathophysiology of depression with component of anxiety.

PMID- 25609597
TI  - Depressive-like behavior is paired to monoaminergic alteration in a murine model
      of Alzheimer's disease.
AB  - BACKGROUND: Neuropsychiatric signs are critical in primary caregiving of
      Alzheimer patients and have not yet been fully investigated in murine models.
      METHODS: 18-month-old 3*Tg-AD male mice and their wild-type male littermates (non
      Tg) were used. The open field test and the elevated plus maze test were used to
      evaluate anxiety-like behaviors, whereas the Porsolt forced swim test, the tail
      suspension test, and the sucrose preference test for antidepressant/depression
      coping behaviors. Neurochemical study was conducted by microdialysis in freely
      moving mice, analyzing the basal and K(+)-stimulated monoamine output in the
      frontal cortex and ventral hippocampus. Moreover by immunohistochemistry, we
      analysed the expression of Tyrosin hydroxylase and Tryptophan hydroxylase, which
      play a key role in the synthesis of monoamines. RESULTS: Aged 3*Tg-AD mice
      exhibited a higher duration of immobility in the forced swim and tail suspension
      tests (predictors of depression-like behavior) which was not attenuated by a
      noradrenaline reuptake inhibitor, desipramine. In the sucrose preference test,
      3*Tg-AD mice showed a significantly lower sucrose preference compared to the non
      Tg group, without any difference in total fluid intake. In contrast, the motor
      functions and anxiety-related emotional responses of 3*Tg-AD mice were normal, as
      detected by the open-field and elevated plus-maze tests. To strengthen these
      results, we then evaluated the monoaminergic neurotransmissions by in vivo
      microdialysis and immunohistochemistry. In particular, with the exception of the
      basal hippocampal dopamine levels, 3*Tg-AD mice exhibited a lower basal
      extracellular output of amines in the frontal cortex and ventral hippocampus and
      also a decreased extracellular response to K(+) stimulation. Such alterations
      occur with obvious local amyloid-beta and tau pathologies and without gross
      alterations in the expression of Tyrosin and Tryptophan hydroxylase. CONCLUSIONS:
      These results suggest that 3*Tg-AD mice exhibit changes in depression-related
      behavior involving aminergic neurotrasmitters and provide an animal model for
      investigating AD with depression.

PMID- 25609599
TI  - Pharmacokinetic and Metabolic Studies of ADTM: A Novel Danshensu Derivative
      Confers Cardioprotection by HPLC-UV and LC-MS/MS.
AB  - (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl)
      propanoate (ADTM) is a novel Danshensu (DSS) derivative regarded as a potential
      new agent for the treatment of myocardial ischemia. A validated high performance
      liquid chromatography (HPLC) approach with a detection limit of 5 ng/mL was used
      for pharmacokinetic evaluation of ADTM in rat plasma. The intra- and interday
      precision in terms of relative standard deviation were <4.98 and 4.84%,
      respectively, at concentration levels of 0.02, 0.20 and 0.80 ug/mL. ADTM's
      absolute oral bioavailability value was 30.4% and t1/2 was 34.33 +/- 11.51 and
      29.94 +/- 8.19 min after oral and intravenous administration of 20 mg/kg. In
      addition, the major metabolites both in vitro and in vivo were 2-hydroxymethy
      3,5,6-trimethylpyrazin and DSS. The results indicated that the hydrolysis was the
      main metabolic pathway of ADTM, and carboxylesterase may play an important role
      in ADTM's metabolism. The present work provides basic information for ADTM's
      further preclinical research and DSS's chemical structure modification. 

PMID- 25609600
TI  - Liquid Chromatographic Method for Simultaneous Quantitation of Clopidogrel,
      Aspirin and Atorvastatin in Rat Plasma and Its Application to the Pharmacokinetic
      Study.
AB  - A simple and robust analytical reversed-phase high-performance liquid
      chromatography method was developed and validated for simultaneous
      chromatographic elution of three cardiovascular drugs, namely clopidogrel,
      aspirin (ASP) and atorvastatin. The method was developed in rat plasma and dosage
      formulation with high-quality chromatographic separation between the drug peaks
      by using a stainless steel analytical column thermo beta-basic, C18 (25 * 0.46
      cm, 5 um). The system was operated at 25 degrees C using a mobile phase
      consisting of acetonitrile and phosphate buffer (pH 3.0) in the gradient ratio at
      a flow rate of 1 mL min(-1) with ultraviolet detection monitored at 232 nm. The
      parametric statistics, i.e., correlation coefficient of 0.999, was assessed for
      all the drugs having linearity over the tested concentration range (10-10,000 ng
      mL(-1)) in rat plasma using an unweighted calibration curve. The accuracy of
      samples for six replicate measurements at lower limit of quantitation level was
      within limit. The method was applicable for the quality control of the mentioned
      drugs in raw material, bulk drug and pharmaceutical formulations as well as in
      pharmacokinetic studies. 

PMID- 25609598
TI  - Proteomic enrichment analysis of psychotic and affective disorders reveals common
      signatures in presynaptic glutamatergic signaling and energy metabolism.
AB  - BACKGROUND: Although genetic studies suggest an overlap in risk alleles across
      the major psychiatric disorders, disease signatures reflecting overlapping
      symptoms have not been found. Profiling studies have identified candidate protein
      markers associated with specific disorders of the psychoaffective spectrum, but
      this has always been done in a selective fashion without accounting for the
      entire proteome composition of the system under investigation. METHODS: Employing
      an orthogonal system-based proteomic enrichment approach based on label-free
      liquid chromatography mass spectrometry, we analyzed anterior prefrontal human
      post-mortem brain tissue of patients affected by schizophrenia (n = 23), bipolar
      disorder (n = 23), major depressive disorder with (n = 12) and without psychotic
      features (n = 11), and healthy controls (n = 23). Labeled selected reaction
      monitoring (SRM) was used to validate these findings on a pathway level.
      Independent in silico analyses of biological annotations revealed common pathways
      across the diseases, associated with presynaptic glutamatergic neurotransmission
      and energy metabolism. We validated the proteomic findings using SRM and
      confirmed that there were no effects of post-mortem confounders. RESULTS:
      Schizophrenia and affective psychosis were linked to a hypoglutamatergic state
      and hypofunction of energy metabolism, while bipolar disorder and major
      depressive disorder were linked to a hyperglutamatergic state and hyperfunction
      of energy metabolism. CONCLUSIONS: These findings support recent investigations,
      which have focused on the therapeutic potential of glutamatergic modulation in
      psychotic and affective disorders. We suggest a disease model in which
      disturbances of the glutamatergic system and ensuing adaptations of neuronal
      energy metabolism are linked to distinct psychiatric symptom dimensions,
      delivering novel evidence for targeted treatment approaches.

PMID- 25609601
TI  - Silica, Hybrid Silica, Hydride Silica and Non-Silica Stationary Phases for Liquid
      Chromatography. Part II: Chemical and Thermal Stability.
AB  - In the first part of this review, stationary phases (silica, hybrid silica,
      hydride silica and non-silica stationary phases) were characterized and compared
      with respect to selectivity, efficiency, resolution, solvent consumption and
      analysis time. The present review focuses on the thermal and chemical stability
      of stationary phases. Stationary phases of high chemical and thermal stability
      are required for separations that are carried over a wide pH and/or temperature
      range. 

PMID- 25609602
TI  - The family series workshop: a community-based psychoeducational intervention.
AB  - This study describes an evaluation of a community-based psychoeducational
      intervention, called The Family Series Workshop, for caregivers of community
      dwelling persons with Alzheimer's disease or related dementias (ADRD). In a one
      group pretest-posttest design, participants (n = 35) attended six weekly
      sessions. Caregiver stress, coping, and caregiving competence were evaluated
      along with demographic characteristics of participants. There was a significant
      improvement found for caregiving competence, and a marginally significant
      increase in coping with humor. Using regression analysis we also found that
      coping with humor, along with stress, were significant predictors of caregiving
      competence. These findings indicate that it is possible to increase caregiving
      competence utilizing a "grassroots" approach and that it is feasible to hold
      educational, group discussions on a plethora of challenging caregiving topics. 

PMID- 25609603
TI  - Serum Uric Acid and Pulse Wave Velocity Among Healthy Adults: Baseline Data From
      the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
AB  - BACKGROUND: We aimed to evaluate a possible association between serum uric acid
      (SUA) levels and carotid-to-femoral pulse wave velocity (cf-PWV) among healthy
      participants of the ELSA-Brasil. METHODS: We excluded subjects using
      antihypertensive medication, diuretics, allopurinol, binge drinkers, body mass
      index (BMI) >35 kg/m2, and those with history of cardiovascular diseases (CVD).
      In a cross-sectional and sex-specific analysis, linear regression models were
      built having cf-PWV as dependent variable and SUA as independent variable.
      Multiple adjustments were subsequently made for age, heart rate and blood
      pressure, BMI, and fasting glucose levels as covariates. Product interaction
      terms were built to test interaction between SUA and other covariates. RESULTS:
      We analyzed 1,875 men and 1,713 women (mean ages, 48.9+/-8.4 and 50.2+/-8.7
      years, respectively). SUA was linearly associated with cf-PWV in men (P = 0.01)
      and in women (P = 0.01). After full adjustment, the association remained
      significant for men (P = 0.01) and no longer significant for women (P = 0.10).
      Fully adjusted linear coefficients beta (95% CI) were 0.06 (0.015; 0.112) and
      0.04 (-0.01; 0.12) in men and women, respectively. Significant interaction
      between SUA and age (P = 0.02) fasting glucose (P < 0.01) and BMI (P = 0.02) was
      found only for women. CONCLUSION: In an apparently healthy population, SUA was
      significantly associated to cf-PWV in men but not in women.

PMID- 25609604
TI  - A message from the editor-in-chief.

PMID- 25609605
TI  - The functional role of astrocyte calcium signaling in cortical blood flow
      regulation.

PMID- 25609606
TI  - Friend or Foe? Perceptual categorization across species.

PMID- 25609607
TI  - Autocrine boost of NMDAR current in hippocampal CA1 pyramidal neurons by a PMCA
      dependent, perisynaptic, extracellular pH shift.
AB  - The plasma membrane Ca(2+)-ATPase (PMCA) is found near postsynaptic NMDARs. This
      transporter is a Ca(2+)-H(+) exchanger that raises cell surface pH. We tested
      whether the PMCA acts in an autocrine fashion to boost pH-sensitive, postsynaptic
      NMDAR currents. In mouse hippocampal slices, NMDAR EPSCs in a singly activated
      CA1 pyramidal neuron were reduced when buffering was augmented by exogenous
      carbonic anhydrase (XCAR). This effect was blocked by the enzyme inhibitor
      benzolamide and mimicked by the addition of HEPES buffer. Similar EPSC reduction
      occurred when PMCA activation was prevented by dialysis of BAPTA or the PMCA
      inhibitor carboxyeosin. Using HEPES, BAPTA, or carboxyeosin, the effect of XCAR
      was completely occluded. XCAR similarly curtailed NMDAR EPSCs of minimal
      amplitude, but had no effect on small AMPAR responses. These results indicate
      that a significant fraction of the postsynaptic NMDAR current is reliant on a
      perisynaptic extracellular alkaline shift generated by the PMCA. 

PMID- 25609608
TI  - Audition-independent vocal crystallization associated with intrinsic
      developmental gene expression dynamics.
AB  - Complex learned behavior is influenced throughout development by both genetic and
      environmental factors. Birdsong, like human speech, is a complex vocal behavior
      acquired through sensorimotor learning and is based on coordinated auditory input
      and vocal output to mimic tutor song. Song is primarily learned during a specific
      developmental stage called the critical period. Although auditory input is
      crucial for acquiring complex vocal patterns, its exact role in neural circuit
      maturation for vocal learning and production is not well understood. Using
      audition-deprived songbirds, we examined whether auditory experience affects
      developmental gene expression in the major elements of neural circuits that
      mediate vocal learning and production. Compared with intact zebra finches, early
      deafened zebra finches showed excessively delayed vocal development, but their
      songs eventually crystallized. In contrast to the different rates of song
      development between the intact and deafened birds, developmental gene expression
      in the motor circuit is conserved in an age-dependent manner from the juvenile
      stage until the older adult stage, even in the deafened birds, which indicates
      the audition-independent robustness of gene expression dynamics during
      development. Furthermore, even after adult deafening, which degrades crystallized
      song, the deteriorated songs ultimately restabilized at the same point when the
      early-deafened birds stabilized their songs. These results indicate a genetic
      program-associated inevitable termination of vocal plasticity that results in
      audition-independent vocal crystallization. 

PMID- 25609609
TI  - A53T human alpha-synuclein overexpression in transgenic mice induces pervasive
      mitochondria macroautophagy defects preceding dopamine neuron degeneration.
AB  - In vitro evidence suggests that the inefficient removal of damaged mitochondria
      by macroautophagy contributes to Parkinson's disease (PD). Using a tissue
      specific gene amplification strategy, we generated a transgenic mouse line with
      human alpha-synuclein A53T overexpression specifically in dopamine (DA) neurons.
      Transgenic mice showed profound early-onset mitochondria abnormalities,
      characterized by macroautophagy marker-positive cytoplasmic inclusions containing
      mainly mitochondrial remnants, which preceded the degeneration of DA neurons.
      Genetic deletion of either parkin or PINK1 in these transgenic mice significantly
      worsened mitochondrial pathologies, including drastically enlarged inclusions and
      loss of total mitochondria contents. These data suggest that mitochondria are the
      main targets of alpha-synuclein and their defective autophagic clearance plays a
      significant role during pathogenesis. Moreover, endogenous PINK1 or parkin is
      indispensable for the proper autophagic removal of damaged mitochondria. Our data
      for the first time establish an essential link between mitochondria
      macroautophagy impairments and DA neuron degeneration in an in vivo model based
      on known PD genetics. The model, its well-defined pathologies, and the
      demonstration of a main pathogenesis pathway in the present study have set the
      stage and direction of emphasis for future studies. 

PMID- 25609611
TI  - Sex-dependent dissociation between emotional appraisal and memory: a large-scale
      behavioral and fMRI study.
AB  - Extensive evidence indicates that women outperform men in episodic memory tasks.
      Furthermore, women are known to evaluate emotional stimuli as more arousing than
      men. Because emotional arousal typically increases episodic memory formation, the
      females' memory advantage might be more pronounced for emotionally arousing
      information than for neutral information. Here, we report behavioral data from
      3398 subjects, who performed picture rating and memory tasks, and corresponding
      fMRI data from up to 696 subjects. We were interested in the interaction between
      sex and valence category on emotional appraisal, memory performances, and fMRI
      activity. The behavioral results showed that females evaluate in particular
      negative (p < 10(-16)) and positive (p = 2 * 10(-4)), but not neutral pictures,
      as emotionally more arousing (pinteraction < 10(-16)) than males. However, in the
      free recall females outperformed males not only in positive (p < 10(-16)) and
      negative (p < 5 * 10(-5)), but also in neutral picture recall (p < 3.4 * 10(-8)),
      with a particular advantage for positive pictures (pinteraction < 4.4 * 10(-10)).
      Importantly, females' memory advantage during free recall was absent in a
      recognition setting. We identified activation differences in fMRI, which
      corresponded to the females' stronger appraisal of especially negative pictures,
      but no activation differences that reflected the interaction effect in the free
      recall memory task. In conclusion, females' valence-category-specific memory
      advantage is only observed in a free recall, but not a recognition setting and
      does not depend on females' higher emotional appraisal. 

PMID- 25609610
TI  - Oligodendroglial maturation is dependent on intracellular protein shuttling.
AB  - Multiple sclerosis is an autoimmune disease of the CNS resulting in degeneration
      of myelin sheaths and loss of oligodendrocytes, which means that protection and
      electrical insulation of axons and rapid signal propagation are impaired, leading
      to axonal damage and permanent disabilities. Partial replacement of lost
      oligodendrocytes and remyelination can occur as a result of activation and
      recruitment of resident oligodendroglial precursor cells. However, the overall
      remyelination capacity remains inefficient because precursor cells often fail to
      generate new oligodendrocytes. Increasing evidence points to the existence of
      several molecular inhibitors that act on these cells and interfere with their
      cellular maturation. The p57kip2 gene encodes one such potent inhibitor of
      oligodendroglial differentiation and this study sheds light on the underlying
      mode of action. We found that subcellular distribution of the p57kip2 protein
      changed during differentiation of rat, mouse, and human oligodendroglial cells
      both in vivo and in vitro. Nuclear export of p57kip2 was correlated with promoted
      myelin expression, higher morphological phenotypes, and enhanced myelination in
      vitro. In contrast, nuclear accumulation of p57kip2 resulted in blocked
      oligodendroglial differentiation. Experimental evidence suggests that the
      inhibitory role of p57kip2 depends on specific interactions with binding proteins
      such as LIMK-1, CDK2, Mash1, and Hes5 either by controlling their site of action
      or their activity. Because functional restoration in demyelinating diseases
      critically depends on the successful generation of oligodendroglial cells, a
      therapeutic need that is currently unmet, the regulatory mechanism described here
      might be of particular interest for identifying suitable drug targets and
      devising novel therapeutic approaches. 

PMID- 25609612
TI  - The spinal muscular atrophy with pontocerebellar hypoplasia gene VRK1 regulates
      neuronal migration through an amyloid-beta precursor protein-dependent mechanism.
AB  - Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH) is an infantile
      SMA variant with additional manifestations, particularly severe microcephaly. We
      previously identified a nonsense mutation in Vaccinia-related kinase 1 (VRK1),
      R358X, as a cause of SMA-PCH. VRK1-R358X is a rare founder mutation in Ashkenazi
      Jews, and additional mutations in patients of different origins have recently
      been identified. VRK1 is a nuclear serine/threonine protein kinase known to play
      multiple roles in cellular proliferation, cell cycle regulation, and
      carcinogenesis. However, VRK1 was not known to have neuronal functions before its
      identification as a gene mutated in SMA-PCH. Here we show that VRK1-R358X
      homozygosity results in lack of VRK1 protein, and demonstrate a role for VRK1 in
      neuronal migration and neuronal stem cell proliferation. Using shRNA in utero
      electroporation in mice, we show that Vrk1 knockdown significantly impairs
      cortical neuronal migration, and affects the cell cycle of neuronal progenitors.
      Expression of wild-type human VRK1 rescues both proliferation and migration
      phenotypes. However, kinase-dead human VRK1 rescues only the migration
      impairment, suggesting the role of VRK1 in neuronal migration is partly
      noncatalytic. Furthermore, we found that VRK1 deficiency in human and mouse leads
      to downregulation of amyloid-beta precursor protein (APP), a known neuronal
      migration gene. APP overexpression rescues the phenotype caused by Vrk1
      knockdown, suggesting that VRK1 affects neuronal migration through an APP
      dependent mechanism. 

PMID- 25609613
TI  - Hyperactivity of newborn Pten knock-out neurons results from increased excitatory
      synaptic drive.
AB  - Developing neurons must regulate morphology, intrinsic excitability, and
      synaptogenesis to form neural circuits. When these processes go awry, disorders,
      including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase
      Pten is mutated in some patients having ASD and seizures, suggesting that its
      mutation disrupts neurological function in part through increasing neuronal
      activity. Supporting this idea, neuronal knock-out of Pten in mice can cause
      macrocephaly, behavioral changes similar to ASD, and seizures. However, the
      mechanisms through which excitability is enhanced following Pten depletion are
      unclear. Previous studies have separately shown that Pten-depleted neurons can
      drive seizures, receive elevated excitatory synaptic input, and have abnormal
      dendrites. We therefore tested the hypothesis that developing Pten-depleted
      neurons are hyperactive due to increased excitatory synaptogenesis using
      electrophysiology, calcium imaging, morphological analyses, and modeling. This
      was accomplished by coinjecting retroviruses to either "birthdate" or birthdate
      and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We
      found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were
      more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane
      potentials, displayed greater peak spike rates, and were more sensitive to
      depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons
      was due, in part, to a higher density of synapses located more proximal to the
      soma. We determined that increased synaptic drive was sufficient to drive
      hypertrophic Pten knock-out neurons beyond their altered action potential
      threshold. Thus, our work contributes a developmental mechanism for the increased
      activity of Pten-depleted neurons. 

PMID- 25609614
TI  - Prefrontal neuronal responses during audiovisual mnemonic processing.
AB  - During communication we combine auditory and visual information.
      Neurophysiological research in nonhuman primates has shown that single neurons in
      ventrolateral prefrontal cortex (VLPFC) exhibit multisensory responses to faces
      and vocalizations presented simultaneously. However, whether VLPFC is also
      involved in maintaining those communication stimuli in working memory or
      combining stored information across different modalities is unknown, although its
      human homolog, the inferior frontal gyrus, is known to be important in
      integrating verbal information from auditory and visual working memory. To
      address this question, we recorded from VLPFC while rhesus macaques (Macaca
      mulatta) performed an audiovisual working memory task. Unlike traditional match
      to-sample/nonmatch-to-sample paradigms, which use unimodal memoranda, our
      nonmatch-to-sample task used dynamic movies consisting of both facial gestures
      and the accompanying vocalizations. For the nonmatch conditions, a change in the
      auditory component (vocalization), the visual component (face), or both
      components was detected. Our results show that VLPFC neurons are activated by
      stimulus and task factors: while some neurons simply responded to a particular
      face or a vocalization regardless of the task period, others exhibited activity
      patterns typically related to working memory such as sustained delay activity and
      match enhancement/suppression. In addition, we found neurons that detected the
      component change during the nonmatch period. Interestingly, some of these neurons
      were sensitive to the change of both components and therefore combined
      information from auditory and visual working memory. These results suggest that
      VLPFC is not only involved in the perceptual processing of faces and
      vocalizations but also in their mnemonic processing. 

PMID- 25609615
TI  - BDNF stimulation of protein synthesis in cortical neurons requires the MAP kinase
      interacting kinase MNK1.
AB  - Although the MAP kinase-interacting kinases (MNKs) have been known for >15 years,
      their roles in the regulation of protein synthesis have remained obscure. Here,
      we explore the involvement of the MNKs in brain-derived neurotrophic factor
      (BDNF)-stimulated protein synthesis in cortical neurons from mice. Using a
      combination of pharmacological and genetic approaches, we show that BDNF-induced
      upregulation of protein synthesis requires MEK/ERK signaling and the downstream
      kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E.
      Translation initiation is mediated by the interaction of eIF4E with the m(7)GTP
      cap of mRNA and with eIF4G. The latter interaction is inhibited by the
      interactions of eIF4E with partner proteins, such as CYFIP1, which acts as a
      translational repressor. We find that BDNF induces the release of CYFIP1 from
      eIF4E, and that this depends on MNK1. Finally, using a novel combination of
      BONCAT and SILAC, we identify a subset of proteins whose synthesis is upregulated
      by BDNF signaling via MNK1 in neurons. Interestingly, this subset of MNK1
      sensitive proteins is enriched for functions involved in neurotransmission and
      synaptic plasticity. Additionally, we find significant overlap between our subset
      of proteins whose synthesis is regulated by MNK1 and those encoded by known FMRP
      binding mRNAs. Together, our data implicate MNK1 as a key component of BDNF
      mediated translational regulation in neurons. 

PMID- 25609616
TI  - ATP binding to synaspsin IIa regulates usage and clustering of vesicles in
      terminals of hippocampal neurons.
AB  - Synaptic transmission is expensive in terms of its energy demands and was
      recently shown to decrease the ATP concentration within presynaptic terminals
      transiently, an observation that we confirm. We hypothesized that, in addition to
      being an energy source, ATP may modulate the synapsins directly. Synapsins are
      abundant neuronal proteins that associate with the surface of synaptic vesicles
      and possess a well defined ATP-binding site of undetermined function. To examine
      our hypothesis, we produced a mutation (K270Q) in synapsin IIa that prevents ATP
      binding and reintroduced the mutant into cultured mouse hippocampal neurons
      devoid of all synapsins. Remarkably, staining for synaptic vesicle markers was
      enhanced in these neurons compared with neurons expressing wild-type synapsin
      IIa, suggesting overly efficient clustering of vesicles. In contrast, the
      mutation completely disrupted the capability of synapsin IIa to slow synaptic
      depression during sustained 10 Hz stimulation, indicating that it interfered with
      synapsin-dependent vesicle recruitment. Finally, we found that the K270Q mutation
      attenuated the phosphorylation of synapsin IIa on a distant PKA/CaMKI consensus
      site known to be essential for vesicle recruitment. We conclude that ATP binding
      to synapsin IIa plays a key role in modulating its function and in defining its
      contribution to hippocampal short-term synaptic plasticity. 

PMID- 25609617
TI  - Evidence for consolidation of neuronal assemblies after seizures in humans.
AB  - The establishment of memories involves reactivation of waking neuronal activity
      patterns and strengthening of associated neural circuits during slow-wave sleep
      (SWS), a process known as "cellular consolidation" (Dudai and Morris, 2013).
      Reactivation of neural activity patterns during waking behaviors that occurs on a
      timescale of seconds to minutes is thought to constitute memory recall (O'Keefe
      and Nadel, 1978), whereas consolidation of memory traces may be revealed and
      served by correlated firing (reactivation) that appears during sleep under
      conditions suitable for synaptic modification (Buhry et al., 2011). Although
      reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et
      al., 2008; Miller et al., 2013), reactivation during sleep has not, likely
      because data are difficult to obtain and the effect is subtle. Seizures, however,
      provide intense and synchronous, yet sparse activation (Bower et al., 2012) that
      could produce a stronger consolidation effect if seizures activate learning
      related mechanisms similar to those activated by learned tasks. Continuous wide
      bandwidth recordings from patients undergoing intracranial monitoring for drug
      resistant epilepsy revealed reactivation of seizure-related neuronal activity
      during subsequent SWS, but not wakefulness. Those neuronal assemblies that were
      most strongly activated during seizures showed the largest correlation changes,
      suggesting that consolidation selectively strengthened neuronal circuits
      activated by seizures. These results suggest that seizures "hijack" physiological
      learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal
      dynamics during post-seizure sleep. 

PMID- 25609618
TI  - Signal transducer and activator of transcription-3 maintains the stemness of
      radial glia at mid-neurogenesis.
AB  - Radial glial cells are stem cell-like populations of glial nature that supply
      neurons either directly or indirectly via basal progenitors that give rise to
      neurons. Here we show that signal transducer and activator of transcription-3
      (STAT3) signaling, a cytokine signaling mediated by Janus tyrosine kinase (Jak),
      is active during neurogenesis in radial glia (RG) but not in basal progenitors.
      Enhanced STAT3 signaling in cortical progenitors caused more RG to persist rather
      than become neurons. Targeted deletion or RNAi-mediated knockdown of Stat3
      resulted in fewer radial glial cells and more basal progenitors and led to
      premature neurogenesis. The neuronal populations affected in Stat3 mutant mice
      were the late-born neurons that constitute the upper cortical layers rather than
      early-born neurons, thus supporting the view that the role of STAT3 at mid
      neurogenesis is layer specific. Analysis of dividing RG revealed that STAT3
      selectively increased the proportion of dividing RG, whereas downregulation of
      STAT3 reduced the proportion. Consistent with this, STAT3 activity in dividing RG
      was associated frequently with vertical cleavage. Pair-cell analysis showed that
      elevated STAT3 activity correlated with symmetric division of RG, producing more
      RG, whereas elimination of STAT3 generated more neurogenic cells. Together, our
      results suggest that STAT3 maintains the stemness of RG and inhibits their
      transition to basal progenitors at mid-neurogenesis, so probably preserving a
      pool of RG for later neurogenesis or gliogenesis. 

PMID- 25609619
TI  - Distribution and function of HCN channels in the apical dendritic tuft of
      neocortical pyramidal neurons.
AB  - The apical tuft is the most remote area of the dendritic tree of neocortical
      pyramidal neurons. Despite its distal location, the apical dendritic tuft of
      layer 5 pyramidal neurons receives substantial excitatory synaptic drive and
      actively processes corticocortical input during behavior. The properties of the
      voltage-activated ion channels that regulate synaptic integration in tuft
      dendrites have, however, not been thoroughly investigated. Here, we use
      electrophysiological and optical approaches to examine the subcellular
      distribution and function of hyperpolarization-activated cyclic nucleotide-gated
      nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out
      patch recordings demonstrated that the amplitude and properties of ensemble HCN
      channel activity were uniform in patches excised from distal apical dendritic
      trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell
      current-clamp recordings revealed that the pharmacological blockade of HCN
      channels decreased voltage compartmentalization and enhanced the generation and
      spread of apical dendritic tuft and trunk regenerative activity. Furthermore,
      multisite two-photon glutamate uncaging demonstrated that HCN channels control
      the amplitude and duration of synaptically evoked regenerative activity in the
      distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and
      somatic recording sites, the blockade of HCN channels decreased excitability.
      Dynamic-clamp experiments revealed that these compartment-specific actions of HCN
      channels were heavily influenced by the local and distributed impact of the high
      density of HCN channels in the distal apical dendritic arbor. The properties and
      subcellular distribution pattern of HCN channels are therefore tuned to regulate
      the interaction between integration compartments in layer 5B pyramidal neurons. 

PMID- 25609621
TI  - The full-length form of the Drosophila amyloid precursor protein is involved in
      memory formation.
AB  - The APP plays a central role in AD, a pathology that first manifests as a memory
      decline. Understanding the role of APP in normal cognition is fundamental in
      understanding the progression of AD, and mammalian studies have pointed to a role
      of secreted APPalpha in memory. In Drosophila, we recently showed that APPL, the
      fly APP ortholog, is required for associative memory. In the present study, we
      aimed to characterize which form of APPL is involved in this process. We show
      that expression of a secreted-APPL form in the mushroom bodies, the center for
      olfactory memory, is able to rescue the memory deficit caused by APPL partial
      loss of function. We next assessed the impact on memory of the Drosophila alpha
      secretase kuzbanian (KUZ), the enzyme initiating the nonamyloidogenic pathway
      that produces secreted APPLalpha. Strikingly, KUZ overexpression not only failed
      to rescue the memory deficit caused by APPL loss of function, it exacerbated this
      deficit. We further show that in addition to an increase in secreted-APPL forms,
      KUZ overexpression caused a decrease of membrane-bound full-length species that
      could explain the memory deficit. Indeed, we observed that transient expression
      of a constitutive membrane-bound mutant APPL form is sufficient to rescue the
      memory deficit caused by APPL reduction, revealing for the first time a role of
      full-length APPL in memory formation. Our data demonstrate that, in addition to
      secreted APPL, the noncleaved form is involved in memory, raising the possibility
      that secreted and full-length APPL act together in memory processes. 

PMID- 25609620
TI  - NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release.
AB  - A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh
      release at Caenorhabditis elegans neuromuscular junctions. Increased evoked
      release is mediated by a presynaptic pathway (egl-30 Galphaq and egl-8 PLCbeta)
      that produces DAG, and by DAG binding to short and long UNC-13 proteins.
      Potentiation of tonic ACh release persists in mutants deficient for egl-30
      Galphaq and egl-8 PLCbeta and requires DAG binding to UNC-13L (but not UNC-13S).
      Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms. 

PMID- 25609623
TI  - Decoding a wide range of hand configurations from macaque motor, premotor, and
      parietal cortices.
AB  - Despite recent advances in decoding cortical activity for motor control, the
      development of hand prosthetics remains a major challenge. To reduce the
      complexity of such applications, higher cortical areas that also represent motor
      plans rather than just the individual movements might be advantageous. We
      investigated the decoding of many grip types using spiking activity from the
      anterior intraparietal (AIP), ventral premotor (F5), and primary motor (M1)
      cortices. Two rhesus monkeys were trained to grasp 50 objects in a delayed task
      while hand kinematics and spiking activity from six implanted electrode arrays
      (total of 192 electrodes) were recorded. Offline, we determined 20 grip types
      from the kinematic data and decoded these hand configurations and the grasped
      objects with a simple Bayesian classifier. When decoding from AIP, F5, and M1
      combined, the mean accuracy was 50% (using planning activity) and 62% (during
      motor execution) for predicting the 50 objects (chance level, 2%) and
      substantially larger when predicting the 20 grip types (planning, 74%; execution,
      86%; chance level, 5%). When decoding from individual arrays, objects and grip
      types could be predicted well during movement planning from AIP (medial array)
      and F5 (lateral array), whereas M1 predictions were poor. In contrast,
      predictions during movement execution were best from M1, whereas F5 performed
      only slightly worse. These results demonstrate for the first time that a large
      number of grip types can be decoded from higher cortical areas during movement
      preparation and execution, which could be relevant for future neuroprosthetic
      devices that decode motor plans. 

PMID- 25609622
TI  - Role of parafacial nuclei in control of breathing in adult rats.
AB  - Contiguous brain regions associated with a given behavior are increasingly being
      divided into subregions associated with distinct aspects of that behavior. Using
      recently developed neuronal hyperpolarizing technologies, we functionally dissect
      the parafacial region in the medulla, which contains key elements of the central
      pattern generator for breathing that are important in central CO2-chemoreception
      and for gating active expiration. By transfecting different populations of
      neighboring neurons with allatostatin or HM4D Gi/o-coupled receptors, we analyzed
      the effect of their hyperpolarization on respiration in spontaneously breathing
      vagotomized urethane-anesthetized rats. We identify two functionally separate
      parafacial nuclei: ventral (pFV) and lateral (pFL). Disinhibition of the pFL with
      bicuculline and strychnine led to active expiration. Hyperpolarizing pFL neurons
      had no effect on breathing at rest, or changes in inspiratory activity induced by
      hypoxia and hypercapnia; however, hyperpolarizing pFL neurons attenuated active
      expiration when it was induced by hypercapnia, hypoxia, or disinhibition of the
      pFL. In contrast, hyperpolarizing pFV neurons affected breathing at rest by
      decreasing inspiratory-related activity, attenuating the hypoxia- and hypercapnia
      induced increase in inspiratory activity, and when present, reducing expiratory
      related abdominal activity. Together with previous observations, we conclude that
      the pFV provides a generic excitatory drive to breathe, even at rest, whereas the
      pFL is a conditional oscillator quiet at rest that, when activated, e.g., during
      exercise, drives active expiration. 

PMID- 25609624
TI  - Metacognitive mechanisms underlying lucid dreaming.
AB  - Lucid dreaming is a state of awareness that one is dreaming, without leaving the
      sleep state. Dream reports show that self-reflection and volitional control are
      more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds,
      lucid dreaming has been associated with metacognition. However, the link to lucid
      dreaming at the neural level has not yet been explored. We sought for
      relationships between the neural correlates of lucid dreaming and thought
      monitoring. Human participants completed a questionnaire assessing lucid dreaming
      ability, and underwent structural and functional MRI. We split participants based
      on their reported dream lucidity. Participants in the high-lucidity group showed
      greater gray matter volume in the frontopolar cortex (BA9/10) compared with those
      in the low-lucidity group. Further, differences in brain structure were mirrored
      by differences in brain function. The BA9/10 regions identified through
      structural analyses showed increases in blood oxygen level-dependent signal
      during thought monitoring in both groups, and more strongly in the high-lucidity
      group. Our results reveal shared neural systems between lucid dreaming and
      metacognitive function, in particular in the domain of thought monitoring. This
      finding contributes to our understanding of the mechanisms enabling higher-order
      consciousness in dreams. 

PMID- 25609625
TI  - Contributions of diverse excitatory and inhibitory neurons to recurrent network
      activity in cerebral cortex.
AB  - The recurrent synaptic architecture of neocortex allows for self-generated
      network activity. One form of such activity is the Up state, in which neurons
      transiently receive barrages of excitatory and inhibitory synaptic inputs that
      depolarize many neurons to spike threshold before returning to a relatively
      quiescent Down state. The extent to which different cell types participate in Up
      states is still unclear. Inhibitory interneurons have particularly diverse
      intrinsic properties and synaptic connections with the local network, suggesting
      that different interneurons might play different roles in activated network
      states. We have studied the firing, subthreshold behavior, and synaptic
      conductances of identified cell types during Up and Down states in layers 5 and
      2/3 in mouse barrel cortex in vitro. We recorded from pyramidal cells and
      interneurons expressing parvalbumin (PV), somatostatin (SOM), vasoactive
      intestinal peptide (VIP), or neuropeptide Y. PV cells were the most active
      interneuron subtype during the Up state, yet the other subtypes also received
      substantial synaptic conductances and often generated spikes. In all cell types
      except PV cells, the beginning of the Up state was dominated by synaptic
      inhibition, which decreased thereafter; excitation was more persistent,
      suggesting that inhibition is not the dominant force in terminating Up states.
      Compared with barrel cortex, SOM and VIP cells were much less active in
      entorhinal cortex during Up states. Our results provide a measure of functional
      connectivity of various neuron types in barrel cortex and suggest differential
      roles for interneuron types in the generation and control of persistent network
      activity. 

PMID- 25609626
TI  - Changes in Purkinje cell simple spike encoding of reach kinematics during
      adaption to a mechanical perturbation.
AB  - The cerebellum is essential in motor learning. At the cellular level, changes
      occur in both the simple spike and complex spike firing of Purkinje cells.
      Because simple spike discharge reflects the main output of the cerebellar cortex,
      changes in simple spike firing likely reflect the contribution of the cerebellum
      to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the
      representation of arm kinematics in Purkinje cell simple spike discharge changed
      during adaptation to mechanical perturbations of reach movements. Monkeys rapidly
      adapted to a novel assistive or resistive perturbation along the direction of the
      reach. Adaptation consisted of matching the amplitude and timing of the
      perturbation to minimize its effect on the reach. In a majority of Purkinje
      cells, simple spike firing recorded before and during adaptation demonstrated
      significant changes in position, velocity, and acceleration sensitivity. The
      timing of the simple spike representations change within individual cells,
      including shifts in predictive versus feedback signals. At the population level,
      feedback-based encoding of position increases early in learning and velocity
      decreases. Both timing changes reverse later in learning. The complex spike
      discharge was only weakly modulated by the perturbations, demonstrating that the
      changes in simple spike firing can be independent of climbing fiber input. In
      summary, we observed extensive alterations in individual Purkinje cell encoding
      of reach kinematics, although the movements were nearly identical in the baseline
      and adapted states. Therefore, adaption to mechanical perturbation of a reaching
      movement is accompanied by widespread modifications in the simple spike encoding.

PMID- 25609627
TI  - Slack channels expressed in sensory neurons control neuropathic pain in mice.
AB  - Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal
      firing activities and patterns. Previous studies identified Slack in sensory
      neurons, but its contribution to acute and chronic pain in vivo remains elusive.
      Here we generated global and sensory neuron-specific Slack mutant mice and
      analyzed their behavior in various animal models of pain. Global ablation of
      Slack led to increased hypersensitivity in models of neuropathic pain, whereas
      the behavior in models of inflammatory and acute nociceptive pain was normal.
      Neuropathic pain behaviors were also exaggerated after ablation of Slack
      selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated
      persisting neuropathic pain behaviors. In conclusion, Slack selectively controls
      the sensory input in neuropathic pain states, suggesting that modulating its
      activity might represent a novel strategy for management of neuropathic pain. 

PMID- 25609628
TI  - Stimulation of monocytes, macrophages, and microglia by amphotericin B and
      macrophage colony-stimulating factor promotes remyelination.
AB  - Approaches to stimulate remyelination may lead to recovery from demyelinating
      injuries and protect axons. One such strategy is the activation of immune cells
      with clinically used medications, since a properly directed inflammatory response
      can have healing properties through mechanisms such as the provision of growth
      factors and the removal of cellular debris. We previously reported that the
      antifungal medication amphotericin B is an activator of circulating monocytes,
      and their tissue-infiltrated counterparts and macrophages, and of microglia
      within the CNS. Here, we describe that amphotericin B activates these cells
      through engaging MyD88/TRIF signaling. When mice were subjected to lysolecithin
      induced demyelination of the spinal cord, systemic injections of nontoxic doses
      of amphotericin B and another activator, macrophage colony-stimulating factor
      (MCSF), further elevated the representation of microglia/macrophages at the site
      of injury. Treatment with amphotericin B, particularly in combination with MCSF,
      increased the number of oligodendrocyte precursor cells and promoted
      remyelination within lesions; these pro-regenerative effects were mitigated in
      mice treated with clodronate liposomes to reduce circulating monocytes and tissue
      infiltrated macrophages. Our results have identified candidates among currently
      used medications as potential therapies for the repair of myelin. 

PMID- 25609629
TI  - Desynchronization of fast-spiking interneurons reduces beta-band oscillations and
      imbalance in firing in the dopamine-depleted striatum.
AB  - Oscillations in the beta-band (8-30 Hz) that emerge in the output nuclei of the
      basal ganglia during Parkinson's disease, along with an imbalanced activation of
      the direct and indirect pathways, have been linked to the hypokinetic motor
      output associated with the disease. Although dopamine depletion causes a change
      in cellular and network properties in the striatum, it is unclear whether
      abnormal activity measured in the globus pallidus and substantia nigra pars
      reticulata is caused by abnormal striatal activity. Here we use a computational
      network model of medium spiny neurons (MSNs)-fast-spiking interneurons (FSIs),
      based on data from several mammalian species, and find that robust beta-band
      oscillations and imbalanced firing emerge from implementation of changes to
      cellular and circuit properties caused by dopamine depletion. These changes
      include a reduction in connections between MSNs, a doubling of FSI inhibition to
      D2 MSNs, an increase in D2 MSN dendritic excitability, and a reduction in D2 MSN
      somatic excitability. The model reveals that the reduced decorrelation between
      MSNs attributable to weakened lateral inhibition enables the strong influence of
      synchronous FSIs on MSN firing and oscillations. Weakened lateral inhibition also
      produces an increased sensitivity of MSN output to cortical correlation, a
      condition relevant to the parkinsonian striatum. The oscillations of FSIs, in
      turn, are strongly modulated by fast electrical transmission between FSIs through
      gap junctions. These results suggest that pharmaceuticals that desynchronize FSI
      activity may provide a novel treatment for the enhanced beta-band oscillations,
      imbalanced firing, and motor dysfunction in Parkinson's disease. 

PMID- 25609630
TI  - Functional mapping of face-selective regions in the extrastriate visual cortex of
      the marmoset.
AB  - The cerebral cortex of humans and macaques has specialized regions for processing
      faces and other visual stimulus categories. It is unknown whether a similar
      functional organization exists in New World monkeys, such as the common marmoset
      (Callithrix jacchus), a species of growing interest as a primate model in
      neuroscience. To address this question, we measured selective neural responses in
      the brain of four awake marmosets trained to fix their gaze upon images of faces,
      bodies, objects, and control patterns. In two of the subjects, we measured high
      gamma-range field potentials from electrocorticography arrays implanted over a
      large portion of the occipital and inferotemporal cortex. In the other two
      subjects, we measured BOLD fMRI responses across the entire brain. Both
      techniques revealed robust, regionally specific patterns of category-selective
      neural responses. We report that at least six face-selective patches mark the
      occipitotemporal pathway of the marmoset, with the most anterior patches showing
      the strongest preference for faces over other stimuli. The similar appearance of
      these patches to previous findings in macaques and humans, including their
      apparent arrangement in two parallel pathways, suggests that core elements of the
      face processing network were present in the common anthropoid primate ancestor
      living ~35 million years ago. The findings also identify the marmoset as a viable
      animal model system for studying specialized neural mechanisms related to high
      level social visual perception in humans. 

PMID- 25609631
TI  - Aging impairs protein-synthesis-dependent long-term memory in Drosophila.
AB  - Although aging is known to impair intermediate-term memory in Drosophila, its
      effect on protein-synthesis-dependent long-term memory (LTM) is unknown. We show
      here that LTM is impaired with age, not due to functional defects in synaptic
      output of mushroom body (MB) neurons, but due to connectivity defects of dorsal
      paired medial (DPM) neurons with their postsynaptic MB neurons. GFP
      reconstitution across synaptic partners (GRASP) experiments revealed structural
      connectivity defects in aged animals of DPM neurons with MB axons in the alpha
      lobe neuropil. As a consequence, a protein-synthesis-dependent LTM trace in the
      alpha/beta MB neurons fails to form. Aging thus impairs protein-synthesis
      dependent LTM along with the alpha/beta MB neuron LTM trace by lessening the
      connectivity of DPM and alpha/beta MB neurons. 

PMID- 25609632
TI  - Corticospinal tract development and spinal cord innervation differ between
      cervical and lumbar targets.
AB  - The corticospinal (CS) tract is essential for voluntary movement, but what we
      know about the organization and development of the CS tract remains limited. To
      determine the total cortical area innervating the seventh cervical spinal cord
      segment (C7), which controls forelimb movement, we injected a retrograde tracer
      (fluorescent microspheres) into C7 such that it would spread widely within the
      unilateral gray matter (to >80%), but not to the CS tract. Subsequent detection
      of the tracer showed that, in both juvenile and adult mice, neurons distributed
      over an unexpectedly broad portion of the rostral two-thirds of the cerebral
      cortex converge to C7. This even included cortical areas controlling the
      hindlimbs (the fourth lumbar segment, L4). With aging, cell densities greatly
      declined, mainly due to axon branch elimination. Whole-cell recordings from
      spinal cord cells upon selective optogenetic stimulation of CS axons, and
      labeling of axons (DsRed) and presynaptic structures (synaptophysin) through
      cotransfection using exo utero electroporation, showed that overgrowing CS axons
      make synaptic connections with spinal cells in juveniles. This suggests that
      neuronal circuits involved in the CS tract to C7 are largely reorganized during
      development. By contrast, the cortical areas innervating L4 are limited to the
      conventional hindlimb area, and the cell distribution and density do not change
      during development. These findings call for an update of the traditional notion
      of somatotopic CS projection and imply that there are substantial developmental
      differences in the cortical control of forelimb and hindlimb movements, at least
      in rodents. 

PMID- 25609633
TI  - Vestibulo-ocular reflex suppression during head-fixed saccades reveals gaze
      feedback control.
AB  - Previous experiments have shown that the vestibulo-ocular reflex (VOR) is
      partially suppressed during large head-free gaze (gaze = eye-in-head + head-in
      space) shifts when both the eyes and head are moving actively, on a fixed body,
      or when the eyes are moving actively and the head passively on a fixed body. We
      tested, in human subjects, the hypothesis that the VOR is also suppressed during
      gaze saccades made with en bloc, head and body together, rotations. Subjects made
      saccades by following a target light. During some trials, the chair rotated so as
      to move the entire body passively before, during, or after a saccade. The
      modulation of the VOR was a function of both saccade amplitude and the time of
      the head perturbation relative to saccade onset. Despite the perturbation, gaze
      remained accurate. Thus, VOR modulation is similar when gaze changes are
      programmed for the eyes alone or for the eyes and head moving together. We
      propose that the brain always programs a change in gaze using feedback based on
      gaze and head signals, rather than on separate eye and head trajectories. 

PMID- 25609635
TI  - Patterned, but not tonic, optogenetic stimulation in motor thalamus improves
      reaching in acute drug-induced Parkinsonian rats.
AB  - High-frequency deep brain stimulation (DBS) in motor thalamus (Mthal) ameliorates
      tremor but not akinesia in Parkinson's disease. The aim of this study was to
      investigate whether there are effective methods of Mthal stimulation to treat
      akinesia. Glutamatergic Mthal neurons, transduced with channelrhodopsin-2 by
      injection of lentiviral vector (Lenti.CaMKII.hChR2(H134R).mCherry), were
      selectively stimulated with blue light (473 nm) via a chronically implanted fiber
      optic probe. Rats performed a reach-to-grasp task in either acute drug-induced
      parkinsonian akinesia (0.03-0.07 mg/kg haloperidol, s.c.) or control (vehicle
      injection) conditions, and the number of reaches was recorded for 5 min before,
      during, and after stimulation. We compared the effect of DBS using complex
      physiological patterns previously recorded in the Mthal of a control rat during
      reaching or exploring behavior, with tonic DBS delivering the same number of
      stimuli per second (rate-control 6.2 or 1.8 Hz, respectively) and with
      stimulation patterns commonly used in other brain regions to treat neurological
      conditions (tonic 130 Hz, theta burst (TBS), and tonic 15 Hz rate-control for
      TBS). Control rats typically executed >150 reaches per 5 min, which was
      unaffected by any of the stimulation patterns. Acute parkinsonian rats executed
      <20 reaches, displaying marked akinesia, which was significantly improved by
      stimulating with the physiological reaching pattern or TBS (both p < 0.05),
      whereas the exploring and all tonic patterns failed to improve reaching. Data
      indicate that the Mthal may be an effective site to treat akinesia, but the
      pattern of stimulation is critical for improving reaching in parkinsonian rats. 

PMID- 25609634
TI  - The potent BACE1 inhibitor LY2886721 elicits robust central Abeta pharmacodynamic
      responses in mice, dogs, and humans.
AB  - BACE1 is a key protease controlling the formation of amyloid beta, a peptide
      hypothesized to play a significant role in the pathogenesis of Alzheimer's
      disease (AD). Therefore, the development of potent and selective inhibitors of
      BACE1 has been a focus of many drug discovery efforts in academia and industry.
      Herein, we report the nonclinical and early clinical development of LY2886721, a
      BACE1 active site inhibitor that reached phase 2 clinical trials in AD. LY2886721
      has high selectivity against key off-target proteases, which efficiently
      translates in vitro activity into robust in vivo amyloid beta lowering in
      nonclinical animal models. Similar potent and persistent amyloid beta lowering
      was observed in plasma and lumbar CSF when single and multiple doses of LY2886721
      were administered to healthy human subjects. Collectively, these data add support
      for BACE1 inhibition as an effective means of amyloid lowering and as an
      attractive target for potential disease modification therapy in AD. 

PMID- 25609636
TI  - Interplay of inhibition and excitation shapes a premotor neural sequence.
AB  - In the zebra finch, singing behavior is driven by a sequence of bursts within
      premotor neurons located in the forebrain nucleus HVC (proper name). In addition
      to these excitatory projection neurons, HVC also contains inhibitory interneurons
      with a role in premotor patterning that is unclear. Here, we used a range of
      electrophysiological and behavioral observations to test previously described
      models suggesting discrete functional roles for inhibitory interneurons in song
      production. We show that single HVC premotor neuron bursts are sufficient to
      drive structured activity within the interneuron network because of pervasive and
      facilitating synaptic connections. We characterize interneuron activity during
      singing and describe reliable pauses in the firing of those neurons. We then
      demonstrate that these gaps in inhibition are likely to be necessary for driving
      normal bursting behavior in HVC premotor neurons and suggest that structured
      inhibition and excitation may be a general mechanism enabling sequence generation
      in other circuits. 

PMID- 25609637
TI  - Cerebellar cortex and cerebellar nuclei are concomitantly activated during
      eyeblink conditioning: a 7T fMRI study in humans.
AB  - There are controversies whether learning of conditioned eyeblink responses
      primarily takes place within the cerebellar cortex, the interposed nuclei, or
      both. It has also been suggested that the cerebellar cortex may be important
      during early stages of learning, and that there is a shift to the cerebellar
      nuclei during later stages. As yet, human studies have provided little to resolve
      this question. In the present study, we established a setup that allows ultra
      high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar
      cortex and interposed cerebellar nuclei simultaneously during delay eyeblink
      conditioning in humans. Event-related fMRI signals increased concomitantly in the
      cerebellar cortex and nuclei during early acquisition of conditioned eyeblink
      responses in 20 healthy human subjects. ANOVAs with repeated-measures showed
      significant effects of time across five blocks of 20 conditioning trials in the
      cortex and nuclei (p < 0.05, permutation corrected). Activations were most
      pronounced in, but not limited to, lobules VI and interposed nuclei. Increased
      activations were most prominent at the first time the maximum number of
      conditioned responses was achieved. Our data are consistent with a simultaneous
      and synergistic two-site model of learning during acquisition of classically
      conditioned eyeblinks. Because increased MRI signal reflects synaptic activity,
      concomitantly increased signals in the cerebellar nuclei and cortex are
      consistent with findings of learning related potentiation at the mossy fiber to
      nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to
      the expression of conditioned responses, however, cannot be excluded. 

PMID- 25609638
TI  - Musical training orchestrates coordinated neuroplasticity in auditory brainstem
      and cortex to counteract age-related declines in categorical vowel perception.
AB  - Musicianship in early life is associated with pervasive changes in brain function
      and enhanced speech-language skills. Whether these neuroplastic benefits extend
      to older individuals more susceptible to cognitive decline, and for whom
      plasticity is weaker, has yet to be established. Here, we show that musical
      training offsets declines in auditory brain processing that accompanying normal
      aging in humans, preserving robust speech recognition late into life. We recorded
      both brainstem and cortical neuroelectric responses in older adults with and
      without modest musical training as they classified speech sounds along an
      acoustic-phonetic continuum. Results reveal higher temporal precision in speech
      evoked responses at multiple levels of the auditory system in older musicians who
      were also better at differentiating phonetic categories. Older musicians also
      showed a closer correspondence between neural activity and perceptual
      performance. This suggests that musicianship strengthens brain-behavior coupling
      in the aging auditory system. Last, "neurometric" functions derived from
      unsupervised classification of neural activity established that early cortical
      responses could accurately predict listeners' psychometric speech identification
      and, more critically, that neurometric profiles were organized more categorically
      in older musicians. We propose that musicianship offsets age-related declines in
      speech listening by refining the hierarchical interplay between
      subcortical/cortical auditory brain representations, allowing more behaviorally
      relevant information carried within the neural code, and supplying more faithful
      templates to the brain mechanisms subserving phonetic computations. Our findings
      imply that robust neuroplasticity conferred by musical training is not restricted
      by age and may serve as an effective means to bolster speech listening skills
      that decline across the lifespan. 

PMID- 25609639
TI  - HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative
      stress-induced neuronal cell death.
AB  - All neurodegenerative diseases are associated with oxidative stress-induced
      neuronal death. Forkhead box O3a (FOXO3a) is a key transcription factor involved
      in neuronal apoptosis. However, how FOXO3a forms complexes and functions in
      oxidative stress processing remains largely unknown. In the present study, we
      show that histone deacetylase 2 (HDAC2) forms a physical complex with FOXO3a,
      which plays an important role in FOXO3a-dependent gene transcription and
      oxidative stress-induced mouse cerebellar granule neuron (CGN) apoptosis.
      Interestingly, we also found that HDAC2 became selectively enriched in the
      promoter region of the p21 gene, but not those of other target genes, and
      inhibited FOXO3a-mediated p21 transcription. Furthermore, we found that oxidative
      stress reduced the interaction between FOXO3a and HDAC2, leading to an increased
      histone H4K16 acetylation level in the p21 promoter region and upregulated p21
      expression in a manner independent of p53 or E2F1. Phosphorylation of HDAC2 at
      Ser 394 is important for the HDAC2-FOXO3a interaction, and we found that cerebral
      ischemia/reperfusion reduced phosphorylation of HDAC2 at Ser 394 and mitigated
      the HDAC2-FOXO3a interaction in mouse brain tissue. Our study reveals the novel
      regulation of FOXO3a-mediated selective gene transcription via epigenetic
      modification in the process of oxidative stress-induced cell death, which could
      be exploited therapeutically. 

PMID- 25609640
TI  - Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord
      injury.
AB  - Spinal cord injury (SCI) patients develop chronic pain involving poorly
      understood central and peripheral mechanisms. Because dysregulation of the
      voltage-gated Kv3.4 channel has been implicated in the hyperexcitable state of
      dorsal root ganglion (DRG) neurons following direct injury of sensory nerves, we
      asked whether such a dysregulation also plays a role in SCI. Kv3.4 channels are
      expressed in DRG neurons, where they help regulate action potential (AP)
      repolarization in a manner that depends on the modulation of inactivation by
      protein kinase C (PKC)-dependent phosphorylation of the channel's inactivation
      domain. Here, we report that, 2 weeks after cervical hemicontusion SCI, injured
      rats exhibit contralateral hypersensitivity to stimuli accompanied by accentuated
      repetitive spiking in putative DRG nociceptors. Also in these neurons at 1 week
      after laminectomy and SCI, Kv3.4 channel inactivation is impaired compared with
      naive nonsurgical controls. At 2-6 weeks after laminectomy, however, Kv3.4
      channel inactivation returns to naive levels. Conversely, Kv3.4 currents at 2-6
      weeks post-SCI are downregulated and remain slow-inactivating.
      Immunohistochemistry indicated that downregulation mainly resulted from decreased
      surface expression of the Kv3.4 channel, as whole-DRG-protein and single-cell
      mRNA transcript levels did not change. Furthermore, consistent with Kv3.4 channel
      dysregulation, PKC activation failed to shorten the AP duration of small-diameter
      DRG neurons. Finally, re-expressing synthetic Kv3.4 currents under dynamic clamp
      conditions dampened repetitive spiking in the neurons from SCI rats. These
      results suggest a novel peripheral mechanism of post-SCI pain sensitization
      implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic
      interventions. 

PMID- 25609641
TI  - Chronic oligodendrogenesis and remyelination after spinal cord injury in mice and
      rats.
AB  - Adult progenitor cells proliferate in the acutely injured spinal cord and their
      progeny differentiate into new oligodendrocytes (OLs) that remyelinate spared
      axons. Whether this endogenous repair continues beyond the first week postinjury
      (wpi), however, is unknown. Identifying the duration of this response is
      essential for guiding therapies targeting improved recovery from spinal cord
      injury (SCI) by enhancing OL survival and/or remyelination. Here, we used two
      PDGFRalpha-reporter mouse lines and rats injected with a GFP-retrovirus to assess
      progenitor fate through 80 d after injury. Surprisingly, new OLs were generated
      as late as 3 months after injury and their processes ensheathed axons near and
      distal to the lesion, colocalized with MBP, and abutted Caspr+ profiles,
      suggesting newly formed myelin. Semithin sections confirmed stereotypical thin OL
      remyelination and few bare axons at 10 wpi, indicating that demyelination is
      relatively rare. Astrocytes in chronic tissue expressed the pro-OL
      differentiation and survival factors CNTF and FGF-2. In addition, pSTAT3+ NG2
      cells were present through at least 5 wpi, revealing active signaling of the
      Jak/STAT pathway in these cells. The progenitor cell fate genes Sox11, Hes5, Id2,
      Id4, BMP2, and BMP4 were dynamically regulated for at least 4 wpi. Collectively,
      these data verify that the chronically injured spinal cord is highly dynamic.
      Endogenous repair, including oligodendrogenesis and remyelination, continues for
      several months after SCI, potentially in response to growth factors and/or
      transcription factor changes. Identifying and understanding spontaneous repair
      processes such as these is important so that beneficial plasticity is not
      inadvertently interrupted and effort is not exerted to needlessly duplicate
      ongoing spontaneous repair. 

PMID- 25609643
TI  - Neural dynamics underlying attentional orienting to auditory representations in
      short-term memory.
AB  - Sounds are ephemeral. Thus, coherent auditory perception depends on "hearing"
      back in time: retrospectively attending that which was lost externally but
      preserved in short-term memory (STM). Current theories of auditory attention
      assume that sound features are integrated into a perceptual object, that multiple
      objects can coexist in STM, and that attention can be deployed to an object in
      STM. Recording electroencephalography from humans, we tested these assumptions,
      elucidating feature-general and feature-specific neural correlates of auditory
      attention to STM. Alpha/beta oscillations and frontal and posterior event-related
      potentials indexed feature-general top-down attentional control to one of several
      coexisting auditory representations in STM. Particularly, task performance during
      attentional orienting was correlated with alpha/low-beta desynchronization (i.e.,
      power suppression). However, attention to one feature could occur without
      simultaneous processing of the second feature of the representation. Therefore,
      auditory attention to memory relies on both feature-specific and feature-general
      neural dynamics. 

PMID- 25609642
TI  - Motoneurons derived from induced pluripotent stem cells develop mature phenotypes
      typical of endogenous spinal motoneurons.
AB  - Induced pluripotent cell-derived motoneurons (iPSCMNs) are sought for use in cell
      replacement therapies and treatment strategies for motoneuron diseases such as
      amyotrophic lateral sclerosis (ALS). However, much remains unknown about the
      physiological properties of iPSCMNs and how they compare with endogenous spinal
      motoneurons or embryonic stem cell-derived motoneurons (ESCMNs). In the present
      study, we first used a proteomic approach and compared protein expression
      profiles between iPSCMNs and ESCMNs to show that <4% of the proteins identified
      were differentially regulated. Like ESCs, we found that mouse iPSCs treated with
      retinoic acid and a smoothened agonist differentiated into motoneurons expressing
      the LIM homeodomain protein Lhx3. When transplanted into the neural tube of
      developing chick embryos, iPSCMNs selectively targeted muscles normally
      innervated by Lhx3 motoneurons. In vitro studies showed that iPSCMNs form
      anatomically mature and functional neuromuscular junctions (NMJs) when cocultured
      with chick myofibers for several weeks. Electrophysiologically, iPSCMNs developed
      passive membrane and firing characteristic typical of postnatal motoneurons after
      several weeks in culture. Finally, iPSCMNs grafted into transected mouse tibial
      nerve projected axons to denervated gastrocnemius muscle fibers, where they
      formed functional NMJs, restored contractile force. and attenuated denervation
      atrophy. Together, iPSCMNs possess many of the same cellular and physiological
      characteristics as ESCMNs and endogenous spinal motoneurons. These results
      further justify using iPSCMNs as a source of motoneurons for cell replacement
      therapies and to study motoneuron diseases such as ALS.

PMID- 25609644
TI  - Synaptic consolidation: from synapses to behavioral modeling.
AB  - Synaptic plasticity, a key process for memory formation, manifests itself across
      different time scales ranging from a few seconds for plasticity induction up to
      hours or even years for consolidation and memory retention. We developed a three
      layered model of synaptic consolidation that accounts for data across a large
      range of experimental conditions. Consolidation occurs in the model through the
      interaction of the synaptic efficacy with a scaffolding variable by a read-write
      process mediated by a tagging-related variable. Plasticity-inducing stimuli
      modify the efficacy, but the state of tag and scaffold can only change if a write
      protection mechanism is overcome. Our model makes a link from depotentiation
      protocols in vitro to behavioral results regarding the influence of novelty on
      inhibitory avoidance memory in rats. 

PMID- 25609646
TI  - Sustaining Reductions in Central Line-Associated Bloodstream Infections in
      Michigan Intensive Care Units: A 10-Year Analysis.
AB  - This article describes the interventions that sustained low central line
      associated bloodstream infection (CLABSI) rates in the Michigan Keystone ICU
      Project. This analysis included data from March 2004 to December 2013 for 121
      intensive care units (ICUs) in 73 hospitals. The Keystone Project was a cohort
      collaborative with an improvement team in each ICU. During the sustainability
      period, teams integrated the intervention into staff orientation, collected and
      submitted monthly data, and reported infection rates to leaders. The annual mean
      rate of BSIs dropped from 2.5 infections/1000 catheter-days in 2004 to 0.76 in
      2013. A subset analysis found nearly double the percentage of ICUs with a mean
      rate of <1 infection/1000 catheter-days in 2013 compared with baseline. Active
      involvement of hospital leaders and the Keystone Center as well as ongoing
      monitoring and feedback of performance were important in sustaining results.
      These findings suggest that large-scale improvement projects can be sustained,
      establishing a new normal for care.

PMID- 25609647
TI  - Variant Creutzfeldt-Jakob disease in older patients.

PMID- 25609645
TI  - A biliverdin-binding cyanobacteriochrome from the chlorophyll d-bearing
      cyanobacterium Acaryochloris marina.
AB  - Cyanobacteriochromes (CBCRs) are linear tetrapyrrole-binding photoreceptors in
      cyanobacteria that absorb visible and near-ultraviolet light. CBCRs are divided
      into two types based on the type of chromophore they contain: phycocyanobilin
      (PCB) or phycoviolobilin (PVB). PCB-binding CBCRs reversibly photoconvert at
      relatively long wavelengths, i.e., the blue-to-red region, whereas PVB-binding
      CBCRs reversibly photoconvert at shorter wavelengths, i.e., the near-ultraviolet
      to green region. Notably, prior to this report, CBCRs containing biliverdin (BV),
      which absorbs at longer wavelengths than do PCB and PVB, have not been found.
      Herein, we report that the typical red/green CBCR AM1_1557 from the chlorophyll d
      bearing cyanobacterium Acaryochloris marina can bind BV almost comparable to PCB.
      This BV-bound holoprotein reversibly photoconverts between a far red light
      absorbing form (Pfr, lambdamax = 697 nm) and an orange light-absorbing form (Po,
      lambdamax = 622 nm). At room temperature, Pfr fluoresces with a maximum at 730
      nm. These spectral features are red-shifted by 48~77 nm compared with those of
      the PCB-bound domain. Because the absorbance of chlorophyll d is red-shifted
      compared with that of chlorophyll a, the BV-bound AM1_1557 may be a
      physiologically relevant feature of A. marina and is potentially useful as an
      optogenetic switch and/or fluorescence imager. 

PMID- 25609648
TI  - Essential gene disruptions reveal complex relationships between phenotypic
      robustness, pleiotropy, and fitness.
AB  - The concept of robustness in biology has gained much attention recently, but a
      mechanistic understanding of how genetic networks regulate phenotypic variation
      has remained elusive. One approach to understand the genetic architecture of
      variability has been to analyze dispensable gene deletions in model organisms;
      however, the most important genes cannot be deleted. Here, we have utilized two
      systems in yeast whereby essential genes have been altered to reduce expression.
      Using high-throughput microscopy and image analysis, we have characterized a
      large number of morphological phenotypes, and their associated variation, for the
      majority of essential genes in yeast. Our results indicate that phenotypic
      robustness is more highly dependent upon the expression of essential genes than
      on the presence of dispensable genes. Morphological robustness appears to be a
      general property of a genotype that is closely related to pleiotropy. While the
      fitness profile across a range of expression levels is idiosyncratic to each
      gene, the global pattern indicates that there is a window in which phenotypic
      variation can be released before fitness effects are observable. 

PMID- 25609649
TI  - Proteomic analyses reveal distinct chromatin-associated and soluble transcription
      factor complexes.
AB  - The current knowledge on how transcription factors (TFs), the ultimate targets
      and executors of cellular signalling pathways, are regulated by protein-protein
      interactions remains limited. Here, we performed proteomics analyses of soluble
      and chromatin-associated complexes of 56 TFs, including the targets of many
      signalling pathways involved in development and cancer, and 37 members of the
      Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass
      spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high
      confident protein-protein interactions. We found that most TFs form very distinct
      protein complexes on and off chromatin. Using this data set, we categorized the
      transcription-related or unrelated regulators for general or specific TFs. Our
      study offers a valuable resource of protein-protein interaction networks for a
      large number of TFs and underscores the general principle that TFs form distinct
      location-specific protein complexes that are associated with the different
      regulation and diverse functions of these TFs. 

PMID- 25609650
TI  - Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome
      reduced bacterium.
AB  - Identifying all essential genomic components is critical for the assembly of
      minimal artificial life. In the genome-reduced bacterium Mycoplasma pneumoniae,
      we found that small ORFs (smORFs; < 100 residues), accounting for 10% of all
      ORFs, are the most frequently essential genomic components (53%), followed by
      conventional ORFs (49%). Essentiality of smORFs may be explained by their
      function as members of protein and/or DNA/RNA complexes. In larger proteins,
      essentiality applied to individual domains and not entire proteins, a notion we
      could confirm by expression of truncated domains. The fraction of essential non
      coding RNAs (ncRNAs) non-overlapping with essential genes is 5% higher than of
      non-transcribed regions (0.9%), pointing to the important functions of the
      former. We found that the minimal essential genome is comprised of 33% (269,410
      bp) of the M. pneumoniae genome. Our data highlight an unexpected hidden layer of
      smORFs with essential functions, as well as non-coding regions, thus changing the
      focus when aiming to define the minimal essential genome.

PMID- 25609651
TI  - Changing partners: transcription factors form different complexes on and off
      chromatin.

PMID- 25609652
TI  - The paratransgenic potential of Lactobacillus kunkeei in the honey bee Apis
      mellifera.
AB  - The honey bee (Apis mellifera) is a domestic insect of high value to human
      societies, as a crop pollinator in agriculture and a model animal in scientific
      research. The honey bee, however, has experienced massive mortality worldwide due
      to the phenomenon Colony Collapse Disorder (CCD), resulting in alarming prospects
      for crop failure in Europe and the USA. The reasons for CCD are complex and much
      debated, but several honey bee pathogens are believed to be involved.
      Paratransgenesis is a Trojan horse strategy, where endogenous microorganisms are
      used to express effector molecules that antagonise pathogen development. For use
      in honey bees, paratransgenesis must rely on a set of criteria that the candidate
      paratransgenic microorganism must fulfil in order to obtain a successful outcome:
      (1) the candidate must be genetically modifiable to express effector molecules;
      (2) the modified organism should have no adverse effects on honey bee health upon
      reintroduction; and (3) it must survive together with other non-pathogenic bee
      associated microorganisms. Lactic acid bacteria (LAB) are common gut bacteria in
      vertebrates and invertebrates, and some have naturally beneficial properties in
      their host. In the present work we aimed to find a potential paratransgenic
      candidate within this bacterial group for use in honey bees. Among isolated LAB
      associated with bee gut microbiota, we found the fructophilic Lactobacillus
      kunkeei to be the most predominant species during foraging seasons. Four
      genetically different strains of L. kunkeei were selected for further assessment.
      We demonstrated (1) that L. kunkeei is transformable; (2) that the transformed
      cells had no obvious adverse effect on honey bee survival; and (3) that
      transformed cells survived well in the gut environment of bees upon
      reintroduction. Our study demonstrates that L. kunkeei fulfils the three criteria
      for paratransgenesis and can be a suitable candidate for further research on this
      strategy in honey bees. 

PMID- 25609653
TI  - Prevention of functional gastrointestinal disorders in neonates: clinical and
      socioeconomic impact.
AB  - Infantile colic, gastro-oesophageal reflux and constipation are the most common
      functional gastrointestinal disorders (FGIDs) affecting infants during the first
      months of life. Despite infantile colic, functional constipation and
      regurgitation had a self-limited pattern, they are considered a risk factor for
      developing different disorders later in life. The pathophysiology of these
      functional diseases is still controversial but there is growing evidence that an
      abnormal gut microbiota colonisation may play a crucial role. An early probiotic
      supplementation could determine a change in colonisation and may represent a new
      strategy for preventing FGIDs. 

PMID- 25609654
TI  - The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal
      dialysis patients: a randomised, double-blind, placebo-controlled trial.
AB  - Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha
      (TNF-alpha) are elevated in dialysis patients and can predict cardiovascular
      events and all-cause mortality. Endotoxin is an important source and also another
      marker of inflammation in patients with chronic kidney disease. The aim of this
      study was to evaluate the impact of oral probiotics on serum levels of
      endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of
      residual renal function, peritonitis episodes, and cardiovascular events were
      also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo
      controlled trial was conducted in PD patients. The intervention group received
      one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9)
      cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and
      10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo
      group received similar capsules containing maltodextrin for the same duration.
      Levels of serum TNF-alpha, interferon gamma, IL-5, IL-6, IL-10, IL-17, and
      endotoxin were measured before and six months after intervention. 39 patients
      completed the study (21 in the probiotics group and 18 in the placebo group). In
      patients receiving probiotics, levels of serum TNF-alpha, IL-5, IL-6, and
      endotoxin significantly decreased after six months of treatment, while levels of
      serum IL-10 significantly increased. In contrast, there were no significant
      changes in levels of serum cytokines and endotoxin in the placebo group after six
      months. In addition, the residual renal function was preserved in patients
      receiving probiotics. In conclusion, probiotics could significantly reduce the
      serum levels of endotoxin, pro-inflammatory cytokines (TNF-alpha and IL-6), IL-5,
      increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve
      residual renal function in PD patients. 

PMID- 25609655
TI  - Gut microbiota composition correlates with changes in body fat content due to
      weight loss.
AB  - Genetics, lifestyle, and dietary habits contribute to metabolic syndrome, but
      also an altered gut microbiota has been identified. Based on this knowledge it is
      suggested that host bacterial composition tends to change in response to dietary
      factors and weight loss. The aim of this study was to identify bacteria affecting
      host metabolism in obesity during weight loss and to correlate them with changes
      of the body composition obtained from bioelectrical impedance analysis (BIA). We
      recruited obese individuals receiving a dietary intervention according DACH
      (German, Austrian, and Swiss Society of Nutrition) reference values and
      guidelines for 'prevention and therapy of obesity' of DAG e.V., DDG, DGE e.V.,
      and DGEM e.V. over three months. Faecal microbiota and BIA measurements were
      conducted at three time points, before, during, and after the intervention. Gut
      microbiota was analysed on the basis of 16S rDNA with quantitative real time PCR.
      Additionally, a food frequency questionnaire with questions to nutritional
      behaviour, lifestyle, and physical activity was administered before intervention.
      After weight reduction, obese individuals showed a significant increase of total
      bacterial abundance. The ratio of Firmicutes/Bacteroidetes significantly
      decreased during intervention. Lactobacilli significantly increased between the
      first and the second time point. These differences also correlated with
      differences in weight percentage. During the intervention period Clostridium
      cluster IV increased significantly between the second and the third time point.
      In contrast Clostridium cluster XIVa showed a decreased abundance. The dominant
      butyrate producer, Faecalibacterium prausnitzii, significantly increased as did
      the abundance of the butyryl-CoA: acetate CoA-transferase gene. Archaea and
      Akkermansia were significantly more prevalent after weight reduction. Our results
      show a clear difference in the gut bacterial composition before and after dietary
      intervention with a rapid change in gut microbial composition after a few weeks,
      but also indicate that a major shift requires long term dietary treatment. 

PMID- 25609656
TI  - 3D-DIP-Chip: a microarray-based method to measure genomic DNA damage.
AB  - Genotoxins cause DNA damage, which can result in genomic instability. The genetic
      changes induced have far-reaching consequences, often leading to diseases such as
      cancer. A wide range of genotoxins exists, including radiations and chemicals
      found naturally in the environment, and in man-made forms created by human
      activity across a variety of industries. Genomic technologies offer the
      possibility of unravelling the mechanisms of genotoxicity, including the repair
      of genetic damage, enhancing our ability to develop, test and safely use existing
      and novel materials. We have developed 3D-DIP-Chip, a microarray-based method to
      measure the prevalence of genomic genotoxin-induced DNA damage. We demonstrate
      the measurement of both physical and chemical induced DNA damage spectra,
      integrating the analysis of these with the associated changes in histone
      acetylation induced in the epigenome. We discuss the application of the method in
      the context of basic and translational sciences. 

PMID- 25609657
TI  - Transmission of tularemia from a water source by transstadial maintenance in a
      mosquito vector.
AB  - Mosquitoes are thought to function as mechanical vectors of Francisella
      tularensis subspecies holarctica (F. t. holarctica) causing tularemia in humans.
      We investigated the clinical relevance of transstadially maintained F. t.
      holarctica in mosquitoes. Aedes egypti larvae exposed to a fully virulent F. t.
      holarctica strain for 24 hours, were allowed to develop into adults when they
      were individually homogenized. Approximately 24% of the homogenates tested
      positive for F. t. DNA in PCR. Mice injected with the mosquito homogenates
      acquired tularemia within 5 days. This novel finding demonstrates the possibility
      of transmission of bacteria by adult mosquitoes having acquired the pathogen from
      their aquatic larval habitats. 

PMID- 25609659
TI  - The Redesign of a Community Pharmacy Internship Program.
AB  - BACKGROUND: Pharmacy internships provide students with practical experiences that
      lead to enhancement of clinical skills and personal growth. OBJECTIVE: To
      describe the design and implementation of a structured 10-week summer pharmacy
      internship program in a supermarket chain pharmacy. METHODS: The pharmacy
      leadership team developed and piloted a new format of the pharmacy internship
      during the summer of 2013. Pharmacy students in professional year 1 (P1), 2 (P2),
      and 4 (P4) were invited to apply for a paid internship. Pharmacy students were
      recruited from all colleges of pharmacy in the state of Michigan. The goal of the
      new program was to create a focused learning opportunity that encouraged students
      to develop knowledge, skills, and abilities about patient care, pharmacy
      management, and working within a team. RESULTS: A total of 19 interns were
      recruited (P1 = 7, P2 = 7, and P4 = 5). Students practiced 40 hours per week and
      participated in the medication dispensing process and employee biometrics
      screening program. Interns provided approximately 500 assessments on pharmacy
      employees and all P1 and P2 interns completed a patient care project.
      CONCLUSIONS: The restructured internship program provided pharmacy students with
      a 10-week program that exposed them to many aspects of community pharmacy
      practice. The program needs future refinement and assessment measures to verify
      interns improve skills throughout the program.

PMID- 25609658
TI  - PACT/RAX regulates the migration of cerebellar granule neurons in the developing
      cerebellum.
AB  - PACT and its murine ortholog RAX were originally identified as a protein
      activator for the dsRNA-dependent, interferon-inducible protein kinase PKR.
      Recent studies indicated that RAX played a role in embryogenesis and neuronal
      development. In this study, we investigated the expression of RAX during the
      postnatal development of the mouse cerebellum and its role in the migration of
      cerebellar granule neurons (CGNs). High expression of RAX was observed in the
      cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from
      the external granule layer (EGL) to the internal granule layer (IGL). The
      migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on
      PD4. This finding was confirmed by in vitro studies showing that RAX knockdown
      impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated
      migration required its third motif and was independent of PKR. PACT/RAX
      interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the
      FAK phosphorylation in CGNs. These findings demonstrated a novel function of
      PACT/RAX in the regulation of neuronal migration. 

PMID- 25609660
TI  - Rapid-onset piperacillin-tazobactam induced thrombocytopenia.
AB  - Thrombocytopenia can occur from a variety of etiologies. Drug-induced
      thrombocytopenia is known to occur with beta-lactam medications, but often in the
      setting of prolonged use. We describe 2 patients who developed rapid-onset
      thrombocytopenia from piperacillin/tazobactam. Other causes of immediate
      thrombocytopenia were excluded. These cases describe a rare presentation of rapid
      onset thrombocytopenia in a commonly used medication. 

PMID- 25609661
TI  - Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of
      Diabetes Mellitus.
AB  - OBJECTIVE: To review clinical evidence for the efficacy, safety, and tolerability
      of dapagliflozin (Farxiga-AstraZeneca), a sodium glucose cotransporter 2
      inhibitor, as monotherapy or in combination with other hypoglycemic agents for
      the treatment of type 2 diabetes. DATA SOURCES: Literature was identified through
      a systematic MEDLINE search of clinical trial results for dapagliflozin. DATA
      SYNTHESIS: Multiple controlled clinical trials have established the efficacy,
      safety, and tolerability of dapagliflozin as monotherapy or in combination with
      other therapies for type 2 diabetes. Dapagliflozin is approved by Food and Drug
      Administration as monotherapy or as an add-on to other glucose lowering agents
      including insulin for the treatment of type 2 diabetes. CONCLUSION: Dapagliflozin
      is effective for the treatment of type 2 diabetes.

PMID- 25609662
TI  - Health Beliefs Describing Patients Enrolling in Community Pharmacy Disease
      Management Programs.
AB  - OBJECTIVES: The purpose of this study was to survey new enrollees in a community
      pharmacy, employer-based diabetes and hypertension coaching program to describe
      the characteristics, health beliefs, and cues to action of newly enrolled
      participants. METHODS: A 70-question, 5-point Likert-type survey was developed
      using constructs from the Health Belief Model (HBM), Theory of Planned Behavior
      (TPB), and Theory of Reasoned Action (TRA). New enrollees in the coaching
      programs completed the survey. Survey responses between controlled and
      uncontrolled patients and patient demographics were compared. RESULTS: Between
      November 2011 and November 2012, 154 patients completed the survey. Patients were
      fairly well controlled with a mean hemoglobin A1C of 7.3% and a mean blood
      pressure of 134/82 mm Hg. The strongest cue to action for enrollment was the
      financial incentives offered by the employer (mean: 3.33, median: 4). White
      patients were significantly more motivated by financial incentives. More patients
      indicated they had not enrolled previously in the program because they were
      unaware it was available (mean: 2.89, median 3.0) and these patients were more
      likely to have an uncontrolled condition (P <= 0.050). CONCLUSION: A top factor
      motivating patients to enroll in a disease management coaching program was the
      receipt of financial incentives. Significant differences in HBM, TPB, and TRA
      responses were seen for patients with different demographics.

PMID- 25609663
TI  - Perceptions, Barriers, and Knowledge of Inpatient Glycemic Control: A Survey of
      Health Care Workers.
AB  - OBJECTIVES: To assess knowledge and perceptions of health care workers regarding
      optimal care for patients with hyperglycemia and identify commonly perceived
      barriers for the development of a hospital-wide education program. RESEARCH
      DESIGN AND METHODS: A cross-sectional design was utilized to survey health care
      workers involved in managing hyperglycemia in an urban, community teaching
      hospital. Each health care worker received a survey specific to their health care
      role. RESULTS: Approximately 50% of questions about best clinical practices were
      answered correctly. Correct responses varied across disciplines (n, mean +/-
      standard deviation [SD]), that is, physicians (n = 112, 53% +/- 26%), nurses (n =
      43, 52% +/- 35%), pharmacists (n = 20, 64% +/- 23%), dietitians (n = 5, 48% +/-
      30%), and patient care assistants (n = 12, 38% +/- 34%). Most health care workers
      perceived hyperglycemia treatment to be very important and that sliding scale
      insulin was commonly used because of convenience but not efficacy. CONCLUSION:
      Knowledge regarding hyperglycemia management was suboptimal across a sample of
      health care workers when compared to clinical best practices. Hyperglycemia
      management was perceived to be important but convenience seemed to influence the
      management approach more than efficacy. Knowledge, perceptions, and barriers seem
      to play an important role in patient care and should be considered when
      developing education programs prior to implementation of optimized glycemic
      protocols.

PMID- 25609664
TI  - An Evaluation of Adverse Drug Reactions Associated With Antipsychotic Use for the
      Treatment of Delirium in the Intensive Care Unit.
AB  - PURPOSE: This investigation evaluated the incidence, severity, and harm of
      adverse drug reactions (ADRs) associated with antipsychotic use for intensive
      care unit (ICU) delirium. METHODS: In this prospective, observational study
      patients were screened for development of delirium with the Intensive Care
      Delirium Screening Checklist (ICDSC). An ICDSC score of >=4 was considered
      delirious. Patients with delirium were screened daily for ADRs. Suspected ADRs
      were evaluated for drug causality using 3 published, objective assessment tools.
      Suspected ADRs were considered positive when 2 of 3 instruments had an agreement
      rating of "possible" or greater. ADR severity was defined as "mild/moderate" or
      "severe" using the National Cancer Institute's Common Terminology Criteria for
      Adverse Events scale. A modified National Coordinating Council Medication Error
      Reporting Index for Categorizing Errors categorized ADRs into "no harm" or
      "harmful." RESULTS: Of 90 patients with delirium, 56 received antipsychotics. Ten
      suspected ADRs occurred attributed to antipsychotic use. QTc prolongation was the
      most observed ADR (50%). Patients with ADRs had higher mean Acute Physiology and
      Chronic Health Evaluation II (APACHE II) scores (P = .038). Patients who received
      haloperidol experienced more severe (P = .048) ADRs. CONCLUSIONS: ADRs were
      observed in 18% of patients having delirium treated with antipsychotics with
      about half considered severe or harmful. A risk versus benefit assessment is
      needed before initiating antipsychotic therapy in ICU patients.

PMID- 25609665
TI  - Holographic optical metasurfaces: a review of current progress.
AB  - In this article, we review recent developments in the field of surface
      electromagnetic wave holography. The holography principle is used as a tool to
      solve an inverse engineering problem consisting of designing novel plasmonic
      interfaces to excite either surface waves or free-space beams with any desirable
      field distributions. Leveraging on the new nanotechnologies to carve
      subwavelength features within the large diffracting apertures of conventional
      holograms, it is now possible to create binary holographic interfaces to shape
      both amplitude phase and polarization of light. The ability of the new generation
      of ultrathin and compact holographic optical devices to fully address light
      properties could find widespread applications in photonics. 

PMID- 25609666
TI  - Increase in the oxidised low-density lipoprotein level by smoking and the
      possible inhibitory effect of statin therapy in patients with cardiovascular
      disease: a retrospective study.
AB  - OBJECTIVES: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) level is a
      marker of oxidative stress and is linked to progression of arteriosclerosis;
      however, the clinical factors affecting the oxidised LDL level have not been
      elucidated. We investigate various factors to identify correlation with MDA-LDL
      level in high-risk patients requiring catheter intervention. SETTING: Secondary
      care (cardiology), single-centre study. PARTICIPANTS: 600 patients who were
      admitted to our hospital and underwent cardiac catheterisation. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Blood samples were obtained to measure lipid profiles
      and MDA-LDL level. RESULTS: With regard to smoking status, MDA-LDL level was
      significantly higher in ex-smokers/current smokers compared with non-smokers. Of
      note, there was no improvement of MDA-LDL level even in patients who had quit
      smoking. Multiple regression analysis showed that MDA-LDL level was positively
      correlated with LDL-cholesterol (LDL-C) level, Brinkman index and male gender.
      The correlation between smoking status and either MDA-LDL or LDL-C level was
      investigated in two groups: namely, patients with and patients without statin
      treatment. In the non-statin group, MDA-LDL level and MDA-LDL/LDL-C ratio were
      significantly higher in ex-smokers/current smokers compared with non-smokers,
      while no significant correlation was observed between smoking status and LDL-C
      level. In contrast, in the statin group, there were no significant correlations
      between smoking status and any of the cholesterol parameters. CONCLUSIONS: We
      found that MDA-LDL level was affected by multiple factors, such as smoking
      status, LDL-C level and male gender. The present findings give additional
      evidence that smoking should be prohibited from a MDA-LDL standpoint.
      Furthermore, statin therapy might have a beneficial effect on the reduction of
      MDA-LDL level.

PMID- 25609667
TI  - Effect of study design and setting on tuberculosis clustering estimates using
      Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU
      VNTR): a systematic review.
AB  - OBJECTIVES: To systematically review the evidence for the impact of study design
      and setting on the interpretation of tuberculosis (TB) transmission using
      clustering derived from Mycobacterial Interspersed Repetitive Units-Variable
      Number Tandem Repeats (MIRU-VNTR) strain typing. DATA SOURCES: MEDLINE, EMBASE,
      CINHAL, Web of Science and Scopus were searched for articles published before
      21st October 2014. REVIEW METHODS: Studies in humans that reported the proportion
      of clustering of TB isolates by MIRU-VNTR were included in the analysis.
      Univariable meta-regression analyses were conducted to assess the influence of
      study design and setting on the proportion of clustering. RESULTS: The search
      identified 27 eligible articles reporting clustering between 0% and 63%. The
      number of MIRU-VNTR loci typed, requiring consent to type patient isolates (as a
      proxy for sampling fraction), the TB incidence and the maximum cluster size
      explained 14%, 14%, 27% and 48% of between-study variation, respectively, and had
      a significant association with the proportion of clustering. CONCLUSIONS:
      Although MIRU-VNTR typing is being adopted worldwide there is a paucity of data
      on how study design and setting may influence estimates of clustering. We have
      highlighted study design variables for consideration in the design and
      interpretation of future studies.

PMID- 25609669
TI  - Correction.

PMID- 25609668
TI  - Correlates of former smoking in patients with cerebrovascular disease: a cross
      sectional study.
AB  - OBJECTIVE: To identify multilevel correlates of former smoking in patients with
      cerebrovascular disease. DESIGN: Secondary data analysis of the Canadian
      Community Health Survey. METHODS: We used data from the 2007-2008 Canadian
      Community Health Survey (CCHS). Smoking status (former smoking vs smoker) was
      described by multilevel correlates of former smoking. A multilevel approach for
      variable selection for this study was used to understand how multiple levels in
      society can have an impact on former smoking. The study sample was selected from
      those respondents of the CCHS that reported they suffered from stroke symptoms.
      Logistic regression was used to predict former smoking in patients with
      cerebrovascular disease while controlling for multilevel confounders. Proportions
      were weighted to reflect the Canadian population. RESULTS: There were 172 355
      respondents who reported to suffer from stroke. From this sample, 36.5% were
      smokers and 63.5% were former smokers. Age groups 55-69 and 70-80 and higher
      education (secondary education +) were positively related to former smoking.
      Household and vehicle smoking restrictions significantly predicted former
      smoking. Counselling advice from a physician and having access to a general
      practitioner were correlates of former smoking. Finally, the use of buproprion
      was positively related to former smoking. CONCLUSIONS: There are multilevel
      correlates of former smoking in smokers with reported stroke symptoms. These
      correlates include older age groups, higher education, household and vehicle
      smoking restrictions, pharmacotherapy use (bupropion), access to a general
      practitioner and counselling advice from a physician.

PMID- 25609670
TI  - VH replacement in primary immunoglobulin repertoire diversification.
AB  - The genes encoding the variable (V) region of the B-cell antigen receptor (BCR)
      are assembled from V, D (diversity), and J (joining) elements through a RAG
      mediated recombination process that relies on the recognition of recombination
      signal sequences (RSSs) flanking the individual elements. Secondary V(D)J
      rearrangement modifies the original Ig rearrangement if a nonproductive original
      joint is formed, as a response to inappropriate signaling from a self-reactive
      BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire.
      VH replacement represents a RAG-mediated secondary rearrangement in which an
      upstream VH element recombines with a rearranged VHDHJH joint to generate a new
      BCR specificity. The rearrangement occurs between the cryptic RSS of the original
      VH element and the conventional RSS of the invading VH gene, leaving behind a
      footprint of up to five base pairs (bps) of the original VH gene that is often
      further obscured by exonuclease activity and N-nucleotide addition. We have
      previously demonstrated that VH replacement can efficiently rescue the
      development of B cells that have acquired two nonproductive heavy chain (IgH)
      rearrangements. Here we describe a novel knock-in mouse model in which the
      prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH
      allele. Using this mouse model, we characterized the role of VH replacement in
      the diversification of the primary Ig repertoire through the modification of
      productive VHDHJH rearrangements. Our results indicate that VH replacement occurs
      before Ig light chain rearrangement and thus is not involved in the editing of
      self-reactive antibodies. 

PMID- 25609672
TI  - Reply to Zayed: Interplay of magnetism and structure in the Shastry-Sutherland
      model.

PMID- 25609671
TI  - Antibody repertoire diversification through VH gene replacement in mice cloned
      from an IgA plasma cell.
AB  - In mammals, VDJ recombination is responsible for the establishment of a highly
      diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy
      (H) chain variable (V) gene rearrangement is thought to prevent further
      recombination at the IgH locus. Here, we describe VHQ52(NT); Vkappagr32(NT) Ig
      monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma
      cell. In VHQ52(NT) mice, IgA replaced IgM to drive early B-cell development and
      peripheral B-cell maturation. In VHQ52(NT) animals, over 20% of mature B cells
      disrupted the single productive, nonautoimmune IgH rearrangement through VH
      replacement and exchanged it with a highly diversified pool of IgH specificities.
      VH replacement occurred in early pro-B cells, was independent of pre-B-cell
      receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH
      replacement was also identified in 5% of peripheral B cells of mice inheriting a
      different productive VH rearrangement expressed in the form of an IgM H chain. In
      summary, editing of a productive IgH rearrangement through VH replacement can
      account for up to 20% of the IgH repertoire expressed by mature B cells. 

PMID- 25609673
TI  - On the origins of antiferromagnetic order in a frustrated spin system at high
      pressure.

PMID- 25609674
TI  - Experimental evolution of sensitivity to a stimulus domain alone is not an
      example of prepared learning.

PMID- 25609675
TI  - Specific Learning Disorders: A Look Inside Children's and Parents' Psychological
      Well-Being and Relationships.
AB  - Despite their ascertained neurobiological origin, specific learning disorders
      (SLD) often have been found to be associated with some emotional disturbances in
      children, and there is growing interest in the environmental and contextual
      variables that may modulate children's developmental trajectories. The present
      study was aimed at evaluating the psychological profile of parents and children
      and the relationships between their measures. Parents of children with SLD (17
      couples, 34 participants) and parents of children with typical development (17
      couples, 34 participants) were administered questionnaires assessing parenting
      styles, reading history, parenting stress, psychopathological indexes, and
      evaluations of children's anxiety and depression. Children (N = 34, 10.7 +/- 1.2
      years) were assessed with self-evaluation questionnaires on anxiety, depression,
      and self-esteem and with a scale assessing their perception of parents'
      qualities. Results showed that parents of children with SLD have higher parental
      distress, poorer reading history, and different parenting styles compared to
      parents of children with TD; there were no differences in psychopathological
      indexes. The SLD group also rated their children as more anxious and depressed.
      Children with SLD had lower scholastic and interpersonal self-esteem, but they
      report ratings of parents' qualities similar to those of TD children.
      Relationships between parents' and children's measures were further explored.
      Implications for research and practice are discussed.

PMID- 25609676
TI  - Revision of the taxonomic status of the species Rhizobium lupini and
      reclassification as Bradyrhizobium lupini comb. nov.
AB  - The species Rhizobium lupini was isolated from Lupinus nodules and included in
      the Approved Lists of Bacterial Names in 1980. Nevertheless, on the basis of the
      analysis of the type strain of this species available in DSMZ, DSM 30140(T),
      whose 16S rRNA gene was identical to that of the type strain of Bradyrhizobium
      japonicum , R. lupini was considered a later synonym of this species. In this
      study we confirmed that the strain DSM 30140(T) belongs to the species B.
      japonicum , but also that it cannot be the original strain of R. lupini because
      this species effectively nodulated Lupinus whereas strain DSM 30140(T) was able
      to nodulate soybean but not Lupinus. Since the original type strain of R. lupini
      was deposited into the USDA collection by L. W. Erdman under the accession number
      USDA 3051(T) we analysed the taxonomic status of this strain showing that
      although it belongs to the genus Bradyrhizobium instead of genus Rhizobium , it
      is phylogenetically distant from B. japonicum and closely related to
      Bradyrhizobium canariense . The type strains R. lupini USDA 3051(T) and B.
      canariense BTA-1(T) share 16S rRNA, recA and glnII gene sequences with
      similarities of 99.8%, 96.5% and 97.1%, respectively. They presented a DNA-DNA
      hybridization value of 36% and also differed in phenotypic characteristics and
      slightly in the proportions of some fatty acids. Therefore we propose the
      reclassification of the species Rhizobium lupini as Bradyrhizobium lupini comb.
      nov. The type strain is USDA 3051(T) ( = CECT 8630(T) = LMG 28514(T)).

PMID- 25609677
TI  - Frigidibacter albus gen. nov., sp. nov., a novel member of the family
      Rhodobacteraceae isolated from lake water.
AB  - Three Gram-staining-negative, strictly aerobic, non-pigmented, non-motile, rod
      shaped bacterial strains, SP32(T) ( = SLM-1(T)), SR68 ( = SLM-3) and SP95 ( = SLM
      2), were isolated from two water samples of a cold-water lake in Xinjiang
      province, China. Growth was observed at 4-25  degrees C and pH 6.0-9.0, and
      optimum growth occurred at 18-20  degrees C and at pH 7.0-7.5. Phylogenetic
      analysis of 16S rRNA gene sequences revealed that these isolates belonged to the
      family Rhodobacteraceae , but formed an evolutionary lineage distinct from other
      species of this family with validly published names. Strain SP32(T) showed the
      highest 16S rRNA gene sequence similarity (96.7%) to Rhodobacter veldkampii ATCC
      35703(T), and the similarity to members of the genera Defluviimonas ,
      Haematobacter and Pseudorhodobacter was respectively 95.8-96.4, 96.0-96.1 and
      95.3-96.1%. The genomic DNA G+C content of strain SP32(T) was 67.6 mol%. The
      major fatty acids (>5%) were summed feature 8 (C(18 : 1)omega7c/C(18 : 1)omega6c)
      and11-methyl C(18 : 1)omega7c. Phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylcholine, one unidentified glycolipid and one
      unidentified polar lipid were the main polar lipids. Ubiquinone 10 (Q-10) was the
      sole respiratory quinone. Strain SP32(T) did not produce photosynthetic pigments
      and did not contain the gene pufM, by which it differed from the phototrophic
      species of the family Rhodobacteraceae . Based on its distinct phenotypic,
      chemotaxonomic and phylogenetic properties, strain SP32(T) represents a novel
      species in a novel genus within the family Rhodobacteraceae , for which we
      propose the name Frigidibacter albus gen. nov., sp. nov. The type strain of
      Frigidibacter albus is strain SP32(T) ( = SLM-1(T) = CGMCC 1.13995(T) = NBRC
      109671(T)).

PMID- 25609678
TI  - Romboutsia sedimentorum sp. nov., isolated from an alkaline-saline lake sediment
      and emended description of the genus Romboutsia.
AB  - A Gram-stain-positive, spore-forming, obligately anaerobic bacterium, designated
      LAM201(T), was isolated from sediment samples from an alkaline-saline lake
      located in Daqing oilfield, Daqing City, PR China. Cells of strain LAM201(T) were
      non-motile and straight or spiral rod-shapes. Strain LAM201(T) was able to
      utilize glucose, fructose, maltose, trehalose and sorbitol as the sole carbon
      source. Acetic acid, ethanol, iso-butanoic acid and iso-valeric acid were the
      main products of glucose fermentation. The major fatty acids of LAM201(T) were
      C(16 : 0) (26.7%) and C(18 : 0) (11.2%). The main polar lipids were four unknown
      glycolipids and five unknown phospholipids. The predominant cell-wall sugars were
      ribose and galactose. The cell-wall peptidoglycan of strain LAM201(T) contained
      alanine, glycine, glutamic acid and aspartic acid. Sodium sulfite was used as the
      electron acceptor. The G+C content of the genomic DNA was 32+/-0.8 mol%, as
      determined by the T(m) method. Analysis of the 16S rRNA gene sequence indicated
      that the isolate belonged to the genus Romboutsia and was most closely related to
      Romboutsia lituseburensis DSM 797(T) and Romboutsia ilealis CRIB(T) with 97.3%
      and 97.2% similarities, respectively. The DNA-DNA hybridization values between
      strain LAM201(T) and the two reference strains were 37% and 31%, respectively. On
      the basis of its phenotypic, phylogenetic and chemotaxonomic characteristics,
      strain LAM201(T) is suggested to represent a novel species within the genus
      Romboutsia , for which the name Romboutsia sedimentorum sp. nov. is proposed. The
      type strain is LAM201(T) ( = ACCC 00717(T) = JCM 19607(T)).

PMID- 25609679
TI  - Frigoribacterium endophyticum sp. nov., an endophytic actinobacterium isolated
      from the root of Anabasis elatior (C. A. Mey.) Schischk.
AB  - A novel endophytic actinobacterium, designated EGI 6500707(T), was isolated from
      the surface-sterilized root of a halophyte Anabasis elatior (C. A. Mey.) Schischk
      collected from Urumqi, Xinjiang province, north-west China, and characterized
      using a polyphasic approach. Cells were Gram-stain-positive, non-motile, short
      rods and produced white colonies. Growth occurred at 10-45  degrees C (optimum 25
      30  degrees C), at pH 5-10 (optimum pH 8) and in presence of 0-4% (w/v) NaCl
      (optimum 0-3%). The predominant menaquinone was MK-9. The diagnostic
      phospholipids were diphosphatidylglycerol and phosphatidylglycerol. The major
      fatty acids were anteiso-C(15 : 0), anteiso-C(17 : 0) and iso-C(16 : 0). The DNA
      G+C content of strain EGI 6500707(T) was 69.1 mol%. Phylogenetic analyses based
      on 16S rRNA gene sequences showed that strain EGI 6500707(T) should be placed in
      the genus Frigoribacterium (family Microbacteriaceae , phylum Actinobacteria ),
      and that the novel strain exhibited the highest 16S rRNA gene sequence similarity
      to Frigoribacterium faeni JCM 11265(T) (99.1%) and Frigoribacterium mesophilum
      MSL-08(T) (96.5%). DNA-DNA relatedness between strain EGI 6500707(T) and F. faeni
      JCM 11265(T) was 47.2%. On the basis of phenotypic and chemotaxonomic
      characteristics, phylogenetic analysis and DNA-DNA relatedness data, strain EGI
      6500707(T) represents a novel species of the genus Frigoribacterium , for which
      the name Frigoribacterium endophyticum sp. nov. is proposed. The type strain is
      EGI 6500707(T) ( = JCM 30093(T) = KCTC 29493(T)).

PMID- 25609680
TI  - Inferiority of vancomycin dosing and design?

PMID- 25609681
TI  - Reply to DiNubile.

PMID- 25609682
TI  - Recommendations for evaluation and management of bone disease in HIV.
AB  - Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries
      contributed to this project, whose primary aim was to provide guidance on the
      screening, diagnosis, and monitoring of bone disease in HIV-infected patients.
      Four clinically important questions in bone disease management were identified,
      and recommendations, based on literature review and expert opinion, were agreed
      upon. Risk of fragility fracture should be assessed primarily using the Fracture
      Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in
      all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged
      >=40 years. DXA should be performed in men aged >=50 years, postmenopausal women,
      patients with a history of fragility fracture, patients receiving chronic
      glucocorticoid treatment, and patients at high risk of falls. In resource-limited
      settings, FRAX without bone mineral density can be substituted for DXA.
      Guidelines for antiretroviral therapy should be followed; adjustment should avoid
      tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients.
      Dietary and lifestyle management strategies for high-risk patients should be
      employed and antiosteoporosis treatment initiated. 

PMID- 25609683
TI  - Trials and tribulations of noninferiority: caveat emptor.

PMID- 25609684
TI  - Renal outcomes among Egyptian lupus nephritis patients: a retrospective analysis
      of 135 cases from a single centre.
AB  - OBJECTIVES: The objective of this paper is to describe renal outcomes in a group
      of Egyptian patients with lupus nephritis and to identify variable prognostic
      factors. PATIENTS AND METHODS: The records of 135 patients (129 females, six
      males) with biopsy-proven lupus nephritis seen between 1999 and 2011 at Kasr Al
      Aini Hospital, Cairo University, were reviewed and included in a retrospective
      analysis. Biopsies were classified according to the WHO classification. Renal
      outcomes were defined according to the Renal Subcommittee of Renal Insufficiency
      of the American College of Rheumatology. RESULTS: The mean follow-up period was
      55.64 +/- 25.68 (range 4-156) months. Thirty-nine patients (29.9%) developed an
      adverse final outcome. This composite outcome, defined as persistent elevation of
      serum creatinine >= 1.2 mg/dl, chronic renal insufficiency, end-stage renal
      disease or death, was seen in 12 (8.9%), seven (5.2%), three (2.2%) and 17
      (12.6%) patients, respectively. The overall patient survival was 93.5% and 87.5%
      at five and 10 years, respectively. Factors associated with an adverse outcome
      included male gender (p = 0.037), hypertension at nephritis onset (p = 0.001),
      serum creatinine >=1.2 mg/dl (p < 0.001), urinary casts (p = 0.006),
      anticardiolipin antibodies (p = 0.03), class IV nephritis (p < 0.001), hyaline
      thrombosis (0.003), glomerular sclerosis (p = 0.002), tubular atrophy(p < 0.001),
      interstitial fibrosis (p < 0.001) and a higher chronicity index (p = 0.006). Time
      dependent factors associated with an adverse outcome included failure to achieve
      remission within the first year, uncontrolled hypertension, persistently low C3
      and development of flares (p = 0.003, < 0.001, = 0.004, = 0.003, respectively).
      CONCLUSION: The association of several adverse prognostic factors with the
      development of poor renal outcome has been confirmed in this study.

PMID- 25609685
TI  - Behavioural and neural basis of anomalous motor learning in children with autism.
AB  - Autism spectrum disorder is a developmental disorder characterized by deficits in
      social and communication skills and repetitive and stereotyped interests and
      behaviours. Although not part of the diagnostic criteria, individuals with autism
      experience a host of motor impairments, potentially due to abnormalities in how
      they learn motor control throughout development. Here, we used behavioural
      techniques to quantify motor learning in autism spectrum disorder, and structural
      brain imaging to investigate the neural basis of that learning in the cerebellum.
      Twenty children with autism spectrum disorder and 20 typically developing control
      subjects, aged 8-12, made reaching movements while holding the handle of a
      robotic manipulandum. In random trials the reach was perturbed, resulting in
      errors that were sensed through vision and proprioception. The brain learned from
      these errors and altered the motor commands on the subsequent reach. We measured
      learning from error as a function of the sensory modality of that error, and
      found that children with autism spectrum disorder outperformed typically
      developing children when learning from errors that were sensed through
      proprioception, but underperformed typically developing children when learning
      from errors that were sensed through vision. Previous work had shown that this
      learning depends on the integrity of a region in the anterior cerebellum. Here we
      found that the anterior cerebellum, extending into lobule VI, and parts of lobule
      VIII were smaller than normal in children with autism spectrum disorder, with a
      volume that was predicted by the pattern of learning from visual and
      proprioceptive errors. We suggest that the abnormal patterns of motor learning in
      children with autism spectrum disorder, showing an increased sensitivity to
      proprioceptive error and a decreased sensitivity to visual error, may be
      associated with abnormalities in the cerebellum. 

PMID- 25609687
TI  - Atrioventricular node ablation in Langendorff-perfused porcine hearts using
      carbon ion particle therapy: methods and an in vivo feasibility investigation for
      catheter-free ablation of cardiac arrhythmias.
AB  - BACKGROUND: Particle therapy, with heavy ions such as carbon-12 ((12)C),
      delivered to arrhythmogenic locations of the heart could be a promising new means
      for catheter-free ablation. As a first investigation, we tested the feasibility
      of in vivo atrioventricular node ablation, in Langendorff-perfused porcine
      hearts, using a scanned 12C beam. METHODS AND RESULTS: Intact hearts were
      explanted from 4 (30-40 kg) pigs and were perfused in a Langendorff organ bath.
      Computed tomographic scans (1 mm voxel and slice spacing) were acquired and (12)C
      ion beam treatment planning (optimal accelerator energies, beam positions, and
      particle numbers) for atrioventricular node ablation was conducted. Orthogonal x
      rays with matching of 4 implanted clips were used for positioning. Ten Gray
      treatment plans were repeatedly administered, using pencil beam scanning. After
      delivery, positron emission tomography-computed tomographic scans for detection
      of beta(+) ((11)C) activity were obtained. A (12)C beam with a full width at half
      maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy
      caused disturbance of atrioventricular conduction with transition into complete
      heart block after 160 Gy. Positron emission computed tomography demonstrated dose
      delivery into the intended area. Application did not induce arrhythmias.
      Macroscopic inspection did not reveal damage to myocardium. Immunostaining
      revealed strong gammaH2AX signals in the target region, whereas no gammaH2AX
      signals were detected in the unirradiated control heart. CONCLUSIONS: This is the
      first report of the application of a (12)C beam for ablation of cardiac tissue to
      treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits
      exploration in intact animal studies as an energy source for arrhythmia
      elimination.

PMID- 25609686
TI  - White matter lesional predictors of chronic visual neglect: a longitudinal study.
AB  - Chronic visual neglect prevents brain-damaged patients from returning to an
      independent and active life. Detecting predictors of persistent neglect as early
      as possible after the stroke is therefore crucial to plan the relevant
      interventions. Neglect signs do not only depend on focal brain lesions, but also
      on dysfunction of large-scale brain networks connected by white matter bundles.
      We explored the relationship between markers of axonal degeneration occurring
      after the stroke and visual neglect chronicity. A group of 45 patients with
      unilateral strokes in the right hemisphere underwent cognitive testing for
      neglect twice, first at the subacute phase (<3 months after onset) and then at
      the chronic phase (>1 year). For each patient, magnetic resonance imaging
      including diffusion sequences was performed at least 4 months after the stroke.
      After masking each patient's lesion, we used tract-based spatial statistics to
      obtain a voxel-wise statistical analysis of the fractional anisotropy data.
      Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of
      these patients had recovered from neglect at follow-up. When compared with
      patients without neglect, the group including all subacute neglect patients had
      decreased fractional anisotropy in the second (II) and third (III) branches of
      the right superior longitudinal fasciculus, as well as in the splenium of the
      corpus callosum. The subgroup of chronic patients showed reduced fractional
      anisotropy in a portion the splenium, the forceps major, which provides
      interhemispheric communication between regions of the occipital lobe and of the
      superior parietal lobules. The severity of neglect correlated with fractional
      anisotropy values in superior longitudinal fasciculus II/III for subacute
      patients and in its caudal portion for chronic patients. Our results confirm a
      key role of fronto-parietal disconnection in the emergence and chronic
      persistence of neglect, and demonstrate an implication of caudal interhemispheric
      disconnection in chronic neglect. Splenial disconnection may prevent fronto
      parietal networks in the left hemisphere from resolving the activity imbalance
      with their right hemisphere counterparts, thus leading to persistent neglect. 

PMID- 25609689
TI  - Effects of dietary pyrroloquinoline quinone disodium on growth, carcass
      characteristics, redox status, and mitochondria metabolism in broilers.
AB  - The potential benefits of supplementing pyrroloquinoline quinone disodium
      (PQQ.Na2) in the diet of broiler chicks were explored. We first examined the
      effect of different levels of dietary PQQ.Na2 on growth performance, carcass
      characteristics, and plasma biochemical parameters (trial 1). A total of 490 1
      day-old male Arbor Acres (AA) broiler chicks were randomly divided into 5 dietary
      groups supplemented with 0, 0.05, 0.1, 0.2, or 0.4 mg PQQ.Na2/kg feed. As the 0.2
      mg/kg PQQ.Na2 supplement gave the best performance, we then investigated whether
      this level of PQQ.Na2 influenced the redox status of plasma samples and
      mitochondrial-related metabolism (trial 2). A total of 120 1-day-old male AA
      chicks were randomly divided into 2 groups supplemented with 0 or 0.2 mg
      PQQ.Na2/kg diet. In trial 1, birds fed a diet containing 0.2 mg PQQ.Na2/kg showed
      lower feed conversion ratio compared with those fed the control diet in the
      overall study (d 1 to 42, P=0.039). Breast muscle yield (d 42) increased
      quadratically in response to dietary PQQ.Na2 supplementation (P=0.021). Analysis
      of plasma biochemical parameters revealed that feeding broiler chicks with <=0.4
      mg/kg PQQ.Na2 did not cause adverse health effects. In trial 2, birds fed 0.2
      mg/kg PQQ.Na2 again showed improved feed efficiency than the control birds in the
      grower and overall phases (P=0.038 and 0.016, respectively). In addition, dietary
      PQQ.Na2 supplementation resulted in a higher anti-oxidative capacity (P=0.001),
      lower redox potential (P=0.008), and higher hepatic citrate synthase activity
      (P=0.002). In contrast, no difference in hepatic mitochondrial DNA copy number
      was observed between the 2 experimental groups (P>0.1). These results indicate
      that PQQ.Na2 is a potentially effective feed additive for improving feed
      efficiency, stimulating breast muscle development, and maintaining redox status
      in broiler chicks. Enhancement of mitochondria efficiency, rather than modulating
      mitochondria numbers, may underlie the growth-promoting effect of PQQ.Na2.

PMID- 25609690
TI  - Effect of daily lithium chloride administration on bone mass and strength in
      growing broiler chickens.
AB  - The objective was to determine the effects of oral lithium chloride
      supplementation on bone strength and mass in broiler chickens. Ninety-six
      broilers were assigned to 1 of 2 treatment groups (lithium chloride or control;
      n=48/treatment). Beginning at 1 or 3 wk of age, chickens were administered
      lithium chloride (20 mg/kg body weight) or water daily by oral gavage. At 6 wk of
      age, chickens were euthanized and bone and muscle samples were collected. A 24 h
      lithium chloride (20 mg/kg body weight) challenge determined that serum lithium
      chloride increased within 2 h and cleared the system within 24 h, demonstrating
      the effective delivery of lithium chloride. Treatment did not influence body
      weight (P>=0.20) or feed intake (P>=0.81), demonstrating that lithium chloride
      did not negatively affect broiler growth. To determine bone strength, 3-point
      bending was performed on the femora and tibiae obtained from control and lithium
      chloride-treated birds in the 1 wk group. Lithium chloride-treated birds had a
      22% reduction in stiffness compared with control in the femora (P=0.02) without a
      corresponding reduction in elastic modulus. No differences were observed in yield
      or ultimate load and in the corresponding calculations of stresses (P>=0.26). The
      toughness of tibiae was not altered in lithium chloride compared with control
      (P=0.11). Bone length and micro-CT imaging were performed on the tibiae of
      control and lithium chloride groups. No differences (P>=0.52) in bone length,
      cortical or trabecular bone volume, trabecular thickness, number, or spacing were
      observed. Lithium chloride treatment did not affect pectoralis muscle color or
      lipid oxidation (P>0.05). In conclusion, lithium chloride treatment in broilers
      did not negatively affect growth or meat quality. A reduction in bone stiffness
      of the femur with lithium chloride treatment was observed, however unlike the
      mouse model, the dosages of lithium chloride used in the current study did not
      result in anabolic effects on broiler long bones.

PMID- 25609688
TI  - Variable activation of the DNA damage response pathways in patients undergoing
      single-photon emission computed tomography myocardial perfusion imaging.
AB  - BACKGROUND: Although single-photon emission computed tomography myocardial
      perfusion imaging (SPECT MPI) has improved the diagnosis and risk stratification
      of patients with suspected coronary artery disease, it remains a primary source
      of low-dose radiation exposure for cardiac patients. To determine the biological
      effects of low-dose radiation from SPECT MPI, we measured the activation of the
      DNA damage response pathways using quantitative flow cytometry and single-cell
      gene expression profiling. METHODS AND RESULTS: Blood samples were collected from
      patients before and after SPECT MPI (n=63). Overall, analysis of all recruited
      patients showed no marked differences in the phosphorylation of proteins (H2AX,
      protein 53, and ataxia telangiectasia mutated) after SPECT. The majority of
      patients also had either downregulated or unchanged expression in DNA damage
      response genes at both 24 and 48 hours post-SPECT. Interestingly, a small subset
      of patients with increased phosphorylation had significant upregulation of genes
      associated with DNA damage, whereas those with no changes in phosphorylation had
      significant downregulation or no difference, suggesting that some patients may
      potentially be more sensitive to low-dose radiation exposure. CONCLUSIONS: Our
      findings showed that SPECT MPI resulted in a variable activation of the DNA
      damage response pathways. Although only a small subset of patients had increased
      protein phosphorylation and elevated gene expression postimaging, continued care
      should be taken to reduce radiation exposure to both the patients and operators.

PMID- 25609691
TI  - Comparison of different ELISA protocols for the detection of IgA against
      influenza nucleoproteins in trachea of vaccinated chickens.
AB  - Vaccines targeting mucosal immunity are important for the control of infection by
      pathogens with mucosal portals of entry, such as avian influenza. However,
      reliable and effective methods for determining levels of mucosal IgA stimulated
      by vaccination are not well developed in poultry and are necessary for
      determining efficacy. The objective of the present study was to compare different
      ELISA protocols to evaluate levels of mucosal IgA against two different sequences
      of nucleoprotein (NP:), a highly conserved internal protein in avian influenza
      virus, in trachea. Positive control tracheas were obtained through
      hyperimmunization of birds with adjuvated NP1 and NP2 peptide conjugated with
      keyhole limpet hemocyanin administered both orally and parenterally; negative
      birds received no antigen. Trachea samples were homogenized, and supernatant
      fluid was collected to separate IgA. ELISA was performed on NP1- or NP2-positive
      trachea samples, negative trachea samples, and blank wells with different levels
      of NP1 and NP2 coating peptides (5 or 10 MUg/mL) using two different secondary
      antibodies (Gene Tex, GT:, or Thermo Scientific, TS:), with or without an acetate
      wash, and using maximum, medium, or low binding ELISA plates. The TS antibody
      resulted in a higher background signal compared to GT. Furthermore, coating plate
      wells with NP2 resulted in very high background compared to NP1. An acetate
      buffer wash resulted in the muffling of signals, and medium and low binding
      plates used in the study resulted in better results than maximum binding plates.
      These results suggest that the selection of appropriate secondary antibodies,
      binding plates, and ELISA reagent protocols all play important roles in
      determining NP1- or NP2-specific IgA levels in trachea samples.

PMID- 25609692
TI  - Electroencephalographic evaluation of the effectiveness of blunt trauma to induce
      loss of consciousness for on-farm killing of chickens and turkeys.
AB  - Euthanasia of small numbers of birds in case of injury or other illness directly
      on the farm may be necessary for welfare reasons. This should be done without
      transportation of the moribund animals in order to minimize pain and distress.
      Blood loss has to be avoided to minimize the risk of contaminating the
      environment. Cervical dislocation in combination with a blunt trauma may be an
      appropriate way to achieve this aim but the bird's age and body weight may
      influence the practicability of this method in the field. In this study, we
      evaluated broilers, broiler breeders, and turkeys of different age groups and
      weights up to nearly 16 kg for the efficacy of blunt trauma to induce
      unconsciousness, allowing subsequent killing of the bird without pain. The effect
      of blunt trauma on the brain was determined by electroencephalography (EEG).
      Auditory evoked potentials (AEPs) were recorded for each animal. Convulsions or
      tonic seizures were observed in all investigated animals after blunt trauma,
      including strong wing movements, torticollis, and stretching of legs. The EEG
      results demonstrate that the blunt trauma induced by a single, sufficiently
      strong hit placed in the frontoparietal region of the head led to a reduction or
      loss of the AEP in all groups of birds. These results clearly indicate a loss of
      sensibility and induction of unconsciousness, which would allow painless killing
      of the birds immediately after the induction of the blunt trauma. 

PMID- 25609693
TI  - Sequence-based genotyping clarifies conflicting historical morphometric and
      biological data for 5 Eimeria species infecting turkeys.
AB  - Unlike with Eimeria species infecting chickens, specific identification and
      nomenclature of Eimeria species infecting turkeys is complicated, and in the
      absence of molecular data, imprecise. In an attempt to reconcile contradictory
      data reported on oocyst morphometrics and biological descriptions of various
      Eimeria species infecting turkey, we established single oocyst derived lines of 5
      important Eimeria species infecting turkeys, Eimeria meleagrimitis (USMN08-01
      strain), Eimeria adenoeides (Guelph strain), Eimeria gallopavonis (Weybridge
      strain), Eimeria meleagridis (USAR97-01 strain), and Eimeria dispersa (Briston
      strain). Short portions (514 bp) of mitochondrial cytochrome c oxidase subunit I
      gene (mt COI) from each were amplified and sequenced. Comparison of these
      sequences showed sufficient species-specific sequence variation to recommend
      these short mt COI sequences as species-specific markers. Uniformity of oocyst
      features (dimensions and oocyst structure) of each pure line was observed.
      Additional morphological features of the oocysts of these species are described
      as useful for the microscopic differentiation of these Eimeria species. Combined
      molecular and morphometric data on these single species lines compared with the
      original species descriptions and more recent data have helped to clarify some
      confusing, and sometimes conflicting, features associated with these Eimeria spp.
      For example, these new data suggest that the KCH and KR strains of E. adenoeides
      reported previously represent 2 distinct species, E. adenoeides and E.
      meleagridis, respectively. Likewise, analysis of the Weybridge strain of E.
      adenoeides, which has long been used as a reference strain in various studies
      conducted on the pathogenicity of E. adenoeides, indicates that this coccidium is
      actually a strain of E. gallopavonis. We highly recommend mt COI sequence-based
      genotyping be incorporated into all studies using Eimeria spp. of turkeys to
      confirm species identifications and so that any resulting data can be associated
      correctly with a single named Eimeria species. 

PMID- 25609694
TI  - ZBTB2 increases PDK4 expression by transcriptional repression of RelA/p65.
AB  - The NF-kappaB is found in almost all animal cell types and is involved in a
      myriad of cellular responses. Aberrant expression of NF-kappaB has been linked to
      cancer, inflammatory diseases and improper development. Little is known about
      transcriptional regulation of the NF-kappaB family member gene RelA/p65. Sp1
      plays a key role in the expression of the RelA/p65 gene. ZBTB2 represses
      transcription of the gene by inhibiting Sp1 binding to a Sp1-binding GC-box in
      the RelA/p65 proximal promoter (bp, -31 to -21). Moreover, recent studies
      revealed that RelA/p65 directly binds to the peroxisome proliferator-activated
      receptor-gamma coactivator1alpha (PGC1alpha) to decrease transcriptional
      activation of the PGC1alpha target gene PDK4, whose gene product inhibits
      pyruvate dehydrogenase (PDH), a key regulator of TCA cycle flux. Accordingly, we
      observed that RelA/p65 repression by ZBTB2 indirectly results in increased PDK4
      expression, which inhibits PDH. Consequently, in cells with ectopic ZBTB2, the
      concentrations of pyruvate and lactate were higher than those in normal cells,
      indicating changes in glucose metabolism flux favoring glycolysis over the TCA
      cycle. Knockdown of ZBTB2 in mouse xenografts decreased tumor growth. ZBTB2 may
      increase cell proliferation by reprogramming glucose metabolic pathways to favor
      glycolysis by upregulating PDK4 expression via repression of RelA/p65 expression.

PMID- 25609695
TI  - Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes
      required for drug-resistance and metastasis in lung cancer.
AB  - Overexpression of Oct4, a stemness gene encoding a transcription factor, has been
      reported in several cancers. However, the mechanism by which Oct4 directs
      transcriptional program that leads to somatic cancer progression remains unclear.
      In this study, we provide mechanistic insight into Oct4-driven transcriptional
      network promoting drug-resistance and metastasis in lung cancer cell, animal and
      clinical studies. Through an integrative approach combining our Oct4 chromatin
      immunoprecipitation sequencing and ENCODE datasets, we identified the genome-wide
      binding regions of Oct4 in lung cancer at promoter and enhancer of numerous genes
      involved in critical pathways which promote tumorigenesis. Notably, PTEN and TNC
      were previously undefined targets of Oct4. In addition, novel Oct4-binding motifs
      were found to overlap with DNA elements for Sp1 transcription factor. We provided
      evidence that Oct4 suppressed PTEN in an Sp1-dependent manner by recruitment of
      HDAC1/2, leading to activation of AKT signaling and drug-resistance. In contrast,
      Oct4 transactivated TNC independent of Sp1 and resulted in cancer metastasis.
      Clinically, lung cancer patients with Oct4 high, PTEN low and TNC high expression
      profile significantly correlated with poor disease-free survival. Our study
      reveals a critical Oct4-driven transcriptional program that promotes lung cancer
      progression, illustrating the therapeutic potential of targeting Oc4
      transcriptionally regulated genes. 

PMID- 25609696
TI  - The Kruppel-associated box repressor domain induces reversible and irreversible
      regulation of endogenous mouse genes by mediating different chromatin states.
AB  - The Kruppel-associated box (KRAB) domain is a transcription repression module
      from the largest family of transcriptional regulators encoded by higher
      vertebrates. We developed a drug-controllable regulation system based on an
      artificial KRAB-containing repressor (tTS) that targets the endogenous Hprt gene
      to explore the regulatory mechanism and molecular basis of KRAB-containing
      regulators within the context of an endogenous gene in vivo. We show that KRAB
      can mediate irreversible and reversible regulation of endogenous genes in mouse
      that is dependent on embryonic developmental stage. KRAB-induced stable DNA
      methylation within the KRAB binding region during the early embryonic stage,
      resulting in irreversible gene repression. In later stages, KRAB mainly induced
      de-acetylation and methylation of histone, resulting in reversible gene
      repression. Thus, we have characterized the KRAB-mediated regulation system
      within the context of an endogenous gene and multiple spatiotemporal ranges,
      thereby providing a basis for identifying the function of KRAB-containing
      regulators and aiding development of novel KRAB-based gene regulation tools in
      vivo. 

PMID- 25609697
TI  - Ad 2.0: a novel recombineering platform for high-throughput generation of
      tailored adenoviruses.
AB  - Recombinant adenoviruses containing a double-stranded DNA genome of 26-45 kb were
      broadly explored in basic virology, for vaccination purposes, for treatment of
      tumors based on oncolytic virotherapy, or simply as a tool for efficient gene
      transfer. However, the majority of recombinant adenoviral vectors (AdVs) is based
      on a small fraction of adenovirus types and their genetic modification.
      Recombineering techniques provide powerful tools for arbitrary engineering of
      recombinant DNA. Here, we adopted a seamless recombineering technology for high
      throughput and arbitrary genetic engineering of recombinant adenoviral DNA
      molecules. Our cloning platform which also includes a novel recombination
      pipeline is based on bacterial artificial chromosomes (BACs). It enables
      generation of novel recombinant adenoviruses from different sources and switching
      between commonly used early generation AdVs and the last generation high-capacity
      AdVs lacking all viral coding sequences making them attractive candidates for
      clinical use. In combination with a novel recombination pipeline allowing cloning
      of AdVs containing large and complex transgenes and the possibility to generate
      arbitrary chimeric capsid-modified adenoviruses, these techniques allow
      generation of tailored AdVs with distinct features. Our technologies will pave
      the way toward broader applications of AdVs in molecular medicine including gene
      therapy and vaccination studies. 

PMID- 25609698
TI  - The solution structure of the pentatricopeptide repeat protein PPR10 upon binding
      atpH RNA.
AB  - The pentatricopeptide repeat (PPR) protein family is a large family of RNA
      binding proteins that is characterized by tandem arrays of a degenerate 35-amino
      acid motif which form an alpha-solenoid structure. PPR proteins influence the
      editing, splicing, translation and stability of specific RNAs in mitochondria and
      chloroplasts ZEA MAYS: PPR10 is amongst the best studied PPR proteins, where
      sequence-specific binding to two RNA transcripts, ATPH: and PSAJ, HAS BEEN
      DEMONSTRATED TO FOLLOW: a recognition code where the identity of two amino acids
      per repeat determines the base-specificity. A recently solved ZmPPR10: PSAJ:
      complex crystal structure suggested a homodimeric complex with considerably fewer
      sequence-specific protein-RNA contacts than inferred PREVIOUSLY: Here we describe
      the solution structure of the ZmPPR10: ATPH: complex using size-exclusion
      chromatography-coupled synchrotron small-angle X-ray scattering (SEC-SY-SAXS).
      Our results support prior evidence that PPR10 binds RNA as a monomer, and that it
      does so in a manner that is commensurate with a canonical and predictable RNA
      binding mode across much of the RNA-protein interface. 

PMID- 25609699
TI  - Enhancer modeling uncovers transcriptional signatures of individual cardiac cell
      states in Drosophila.
AB  - Here we used discriminative training methods to uncover the chromatin,
      transcription factor (TF) binding and sequence features of enhancers underlying
      gene expression in individual cardiac cells. We used machine learning with TF
      motifs and ChIP data for a core set of cardiogenic TFs and histone modifications
      to classify Drosophila cell-type-specific cardiac enhancer activity. We show that
      the classifier models can be used to predict cardiac cell subtype cis-regulatory
      activities. Associating the predicted enhancers with an expression atlas of
      cardiac genes further uncovered clusters of genes with transcription and function
      limited to individual cardiac cell subtypes. Further, the cell-specific enhancer
      models revealed chromatin, TF binding and sequence features that distinguish
      enhancer activities in distinct subsets of heart cells. Collectively, our results
      show that computational modeling combined with empirical testing provides a
      powerful platform to uncover the enhancers, TF motifs and gene expression
      profiles which characterize individual cardiac cell fates. 

PMID- 25609701
TI  - Lean mass index, body fat and survival in Chinese patients with coronary artery
      disease.
AB  - BACKGROUND: 'Obesity paradox' was not consistently observed in Asians with
      coronary artery disease (CAD). AIM: The study investigated the association
      between body composition and outcomes in Chinese patients with CAD. DESIGN:
      Cohort study. METHOD: A total of 3280 patients with angiographically validated
      CAD were consecutively included. Body fat (BF) percentage and lean mass index
      (LMI) were evaluated using the Clinica Universidad de Navarra-Body Adiposity
      Estimator. The rate of mortality from any cause was compared across groups
      classified by the quartiles of LMI. RESULTS: During a median period of 24 months,
      288 (8.8%) participants died. There was a close association between increasing
      LMI and reducing mortality rate. However, univariate analyses did not find
      protective effect of BF on survival. After adjusting for age, sex, diabetes,
      current smoking, systolic blood pressure, creatinine, white blood cell count,
      haemoglobin and medication, Cox regression analyses showed that the significant
      relation between higher quartiles (Q) of LMI and survival benefit (Q4, hazard
      ratio 0.58 (95% confidence interval: 0.36-0.94) vs. Q3, 0.60 (0.39-0.91) vs. Q2,
      0.60 (0.41-0.88) vs. Q1, reference) remained. CONCLUSION: Low LMI but not BF
      predicts all-cause mortality in Chinese patients with CAD.

PMID- 25609700
TI  - RPI-Pred: predicting ncRNA-protein interaction using sequence and structural
      information.
AB  - RNA-protein complexes are essential in mediating important fundamental cellular
      processes, such as transport and localization. In particular, ncRNA-protein
      interactions play an important role in post-transcriptional gene regulation like
      mRNA localization, mRNA stabilization, poly-adenylation, splicing and
      translation. The experimental methods to solve RNA-protein interaction prediction
      problem remain expensive and time-consuming. Here, we present the RPI-Pred (RNA
      protein interaction predictor), a new support-vector machine-based method, to
      predict protein-RNA interaction pairs, based on both the sequences and
      structures. The results show that RPI-Pred can correctly predict RNA-protein
      interaction pairs with ~94% prediction accuracy when using sequence and
      experimentally determined protein and RNA structures, and with ~83% when using
      sequences and predicted protein and RNA structures. Further, our proposed method
      RPI-Pred was superior to other existing ones by predicting more experimentally
      validated ncRNA-protein interaction pairs from different organisms. Motivated by
      the improved performance of RPI-Pred, we further applied our method for reliable
      construction of ncRNA-protein interaction networks. The RPI-Pred is publicly
      available at: http://ctsb.is.wfubmc.edu/projects/rpi-pred. 

PMID- 25609702
TI  - How should specialist competencies in heart valve disease be recognized?

PMID- 25609703
TI  - The focal adhesion protein PINCH-1 associates with EPLIN at integrin adhesion
      sites.
AB  - PINCH-1 is a LIM-only domain protein that forms a ternary complex with integrin
      linked kinase (ILK) and parvin (to form the IPP complex) downstream of integrins.
      Here, we demonstrate that PINCH-1 (also known as Lims1) gene ablation in the
      epidermis of mice caused epidermal detachment from the basement membrane,
      epidermal hyperthickening and progressive hair loss. PINCH-1-deficient
      keratinocytes also displayed profound adhesion, spreading and migration defects
      in vitro that were substantially more severe than those of ILK-deficient
      keratinocytes indicating that PINCH-1 also exerts functions in an ILK-independent
      manner. By isolating the PINCH-1 interactome, the LIM-domain-containing and actin
      binding protein epithelial protein lost in neoplasm (EPLIN, also known as LIMA1)
      was identified as a new PINCH-1-associated protein. EPLIN localized, in a PINCH-1
      dependent manner, to integrin adhesion sites of keratinocytes in vivo and in
      vitro and its depletion severely attenuated keratinocyte spreading and migration
      on collagen and fibronectin without affecting PINCH-1 levels in focal adhesions.
      Given that the low PINCH-1 levels in ILK-deficient keratinocytes were sufficient
      to recruit EPLIN to integrin adhesions, our findings suggest that PINCH-1
      regulates integrin-mediated adhesion of keratinocytes through the interactions
      with ILK as well as EPLIN. 

PMID- 25609705
TI  - A new cytoplasmic interaction between junctin and ryanodine receptor Ca2+ release
      channels.
AB  - Junctin, a non-catalytic splice variant encoded by the aspartate-beta-hydroxylase
      (Asph) gene, is inserted into the membrane of the sarcoplasmic reticulum (SR)
      Ca(2+) store where it modifies Ca(2+) signalling in the heart and skeletal muscle
      through its regulation of ryanodine receptor (RyR) Ca(2+) release channels.
      Junctin is required for normal muscle function as its knockout leads to abnormal
      Ca(2+) signalling, muscle dysfunction and cardiac arrhythmia. However, the nature
      of the molecular interaction between junctin and RyRs is largely unknown and was
      assumed to occur only in the SR lumen. We find that there is substantial binding
      of RyRs to full junctin, and the junctin luminal and, unexpectedly, cytoplasmic
      domains. Binding of these different junctin domains had distinct effects on RyR1
      and RyR2 activity: full junctin in the luminal solution increased RyR channel
      activity by ~threefold, the C-terminal luminal interaction inhibited RyR channel
      activity by ~50%, and the N-terminal cytoplasmic binding produced an ~fivefold
      increase in RyR activity. The cytoplasmic interaction between junctin and RyR is
      required for luminal binding to replicate the influence of full junctin on RyR1
      and RyR2 activity. The C-terminal domain of junctin binds to residues including
      the S1-S2 linker of RyR1 and N-terminal domain of junctin binds between RyR1
      residues 1078 and 2156. 

PMID- 25609704
TI  - Unconventional PINK1 localization to the outer membrane of depolarized
      mitochondria drives Parkin recruitment.
AB  - Dysfunction of PTEN-induced putative kinase 1 (PINK1), a Ser/Thr kinase with an N
      terminal mitochondrial-targeting sequence (MTS), causes familial recessive
      parkinsonism. Reduction of the mitochondrial membrane potential limits MTS
      mediated matrix import and promotes PINK1 accumulation on the outer mitochondrial
      membrane (OMM) of depolarized mitochondria. PINK1 then undergoes
      autophosphorylation and phosphorylates ubiquitin and Parkin, a cytosolic
      ubiquitin ligase, for clearance of damaged mitochondria. The molecular basis for
      PINK1 localization on the OMM of depolarized mitochondria rather than release to
      the cytosol is poorly understood. Here, we disentangle the PINK1 localization
      mechanism using deletion mutants and a newly established constitutively active
      PINK1 mutant. Disruption of the MTS through N-terminal insertion of aspartic acid
      residues results in OMM localization of PINK1 in energized mitochondria.
      Unexpectedly, the MTS and putative transmembrane domain (TMD) are dispensable for
      OMM localization, whereas mitochondrial translocase Tom40 (also known as TOMM40)
      and an alternative mitochondrial localization signal that resides between the MTS
      and TMD are required. PINK1 utilizes a mitochondrial localization mechanism that
      is distinct from that of conventional MTS proteins and that presumably functions
      in conjunction with the Tom complex in OMM localization when the conventional N
      terminal MTS is inhibited. 

PMID- 25609706
TI  - Aminopeptidase P3, a new member of the TNF-TNFR2 signaling complex, induces
      phosphorylation of JNK1 and JNK2.
AB  - Tumor necrosis factor (TNF) is an important mediator that triggers onset of
      autoimmune diseases and exerts its biological effects by interacting through two
      receptors, TNFR1 (also known as TNFRSF1A) and TNFR2 (also known as TNFRSF1B).
      TNFR2 signaling has significant potential to exert pro-survival and protective
      roles in several diseases. Unlike TNFR1 signaling, however, the mechanism of
      TNFR2 signal transduction is poorly understood, and few of its adaptor molecules
      are known. The present study utilized a proteomics approach to search for adaptor
      molecules in the TNFR2 signaling complex and identified aminopeptidase P3 (APP3,
      also known as XPNPEP3) to be a key molecule. One of its two isoforms,
      mitochondrial APP3 (APP3m) but not cytosolic APP3 (APP3c), was recruited to TNFR2
      and shown to regulate TNF-TNFR2-dependent phosphorylation of JNK1 (also known as
      MAPK8) and JNK2 (also known as MAPK9). Furthermore, APP3m was released from
      mitochondria upon TNF stimulation in the absence of mitochondrial outer membrane
      permeabilization (MOMP). The observation of increased cell death upon
      downregulation of APP3m also suggested that APP3m exerts an anti-apoptotic
      function. These findings reveal that APP3m is a new member of the TNF-TNFR2
      signaling complex and characterize an APP3-mediated TNFR2 signal transduction
      mechanism that induces activation of JNK1 and JNK2. 

PMID- 25609707
TI  - Subnuclear domain proteins in cancer cells support the functions of RUNX2 in the
      DNA damage response.
AB  - Cancer cells exhibit modifications in nuclear architecture and transcriptional
      control. Tumor growth and metastasis are supported by RUNX family transcriptional
      scaffolding proteins, which mediate the assembly of nuclear-matrix-associated
      gene-regulatory hubs. We used proteomic analysis to identify RUNX2-dependent
      protein-protein interactions associated with the nuclear matrix in bone, breast
      and prostate tumor cell types and found that RUNX2 interacts with three distinct
      proteins that respond to DNA damage - RUVBL2, INTS3 and BAZ1B. Subnuclear foci
      containing these proteins change in intensity or number following UV irradiation.
      Furthermore, RUNX2, INTS3 and BAZ1B form UV-responsive complexes with the serine
      139-phosphorylated isoform of H2AX (gammaH2AX). UV irradiation increases the
      interaction of BAZ1B with gammaH2AX and decreases histone H3 lysine 9 acetylation
      levels, which mark accessible chromatin. RUNX2 depletion prevents the BAZ1B
      gammaH2AX interaction and attenuates loss of H3K9 and H3K56 acetylation. Our data
      are consistent with a model in which RUNX2 forms functional complexes with BAZ1B,
      RUVBL2 and INTS3 to mount an integrated response to DNA damage. This proposed
      cytoprotective function for RUNX2 in cancer cells might clarify its expression in
      chemotherapy-resistant and/or metastatic tumors.

PMID- 25609708
TI  - Activin A inhibits RANKL-mediated osteoclast formation, movement and function in
      murine bone marrow macrophage cultures.
AB  - The process of osteoclastic bone resorption is complex and regulated at multiple
      levels. The role of osteoclast (OCL) fusion and motility in bone resorption are
      unclear, with the movement of OCL on bone largely unexplored. RANKL (also known
      as TNFSF11) is a potent stimulator of murine osteoclastogenesis, and activin A
      (ActA) enhances that stimulation in whole bone marrow. ActA treatment does not
      induce osteoclastogenesis in stroma-free murine bone marrow macrophage cultures
      (BMM), but rather inhibits RANKL-induced osteoclastogenesis. We hypothesized that
      ActA and RANKL differentially regulate osteoclastogenesis by modulating OCL
      precursors and mature OCL migration. Time-lapse video microscopy measured ActA
      and RANKL effects on BMM and OCL motility and function. ActA completely inhibited
      RANKL-stimulated OCL motility, differentiation and bone resorption, through a
      mechanism mediated by ActA-dependent changes in SMAD2, AKT1 and inhibitor of
      nuclear factor kappaB (IkappaB) signaling. The potent and dominant inhibitory
      effect of ActA was associated with decreased OCL lifespan because ActA
      significantly increased activated caspase-3 in mature OCL and OCL precursors.
      Collectively, these data demonstrate a dual action for ActA on murine OCLs.

PMID- 25609709
TI  - Unconventional molecular regulation of synaptic vesicle replenishment in cochlear
      inner hair cells.
AB  - Ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle
      replenishment to indefatigably encode sound. In neurons, neuroendocrine and
      immune cells, vesicle replenishment depends on proteins of the mammalian
      uncoordinated 13 (Munc13, also known as Unc13) and Ca(2+)-dependent activator
      proteins for secretion (CAPS) families, which prime vesicles for exocytosis.
      Here, we tested whether Munc13 and CAPS proteins also regulate exocytosis in
      mouse IHCs by combining immunohistochemistry with auditory systems physiology and
      IHC patch-clamp recordings of exocytosis in mice lacking Munc13 and CAPS
      isoforms. Surprisingly, we did not detect Munc13 or CAPS proteins at IHC
      presynaptic active zones and found normal IHC exocytosis as well as auditory
      brainstem responses (ABRs) in Munc13 and CAPS deletion mutants. Instead, we show
      that otoferlin, a C2-domain protein that is crucial for vesicular fusion and
      replenishment in IHCs, clusters at the plasma membrane of the presynaptic active
      zone. Electron tomography of otoferlin-deficient IHC synapses revealed a
      reduction of short tethers holding vesicles at the active zone, which might be a
      structural correlate of impaired vesicle priming in otoferlin-deficient IHCs. We
      conclude that IHCs use an unconventional priming machinery that involves
      otoferlin. 

PMID- 25609710
TI  - MiR-145 suppresses embryo-epithelial juxtacrine communication at implantation by
      modulating maternal IGF1R.
AB  - Successful implantation requires the synchronization of viable embryonic
      development with endometrial receptivity. The mechanisms allowing for the
      initiation of crosstalk between the embryo and the endometrium remain elusive;
      however, recent studies have revealed that there are alterations in endometrial
      microRNAs (miRs) in women suffering repeated implantation failure and that one of
      the altered miRs is miR-145. We assessed the role of miR-145 and its target
      IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were
      achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and
      3'UTR luciferase reporter assays confirmed that IGF1R is a direct target of miR
      145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to
      endometrial epithelial cells was used to study the effects of altered miR-145
      and/or IGF1R expression on early implantation events. miR-145 overexpression or
      specific reduction of IGF1R impaired attachment in both cases. An IGF1R target
      protector prevented the miR-145-mediated reduction in IGF1R and reversed the
      effect of miR-145 overexpression on attachment. The data demonstrate that miR-145
      influences embryo attachment by reducing the level of IGF1R in endometrium.

PMID- 25609711
TI  - EPLIN is a crucial regulator for extrusion of RasV12-transformed cells.
AB  - At the initial stage of carcinogenesis, a mutation occurs in a single cell within
      a normal epithelial layer. We have previously shown that RasV12-transformed cells
      are apically extruded from the epithelium when surrounded by normal cells.
      However, the molecular mechanisms underlying this phenomenon remain elusive.
      Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as
      LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal
      cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion
      of RasV12-transformed cells, suggesting their positive role in the elimination of
      transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects
      its enrichment in RasV12-transformed cells that are surrounded by normal cells.
      Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and
      protein kinase A (PKA) in RasV12-transformed cells. In addition, EPLIN
      substantially affects the accumulation of filamin A, a vital player in epithelial
      defense against cancer (EDAC), in the neighboring normal cells, and vice versa.
      These results indicate that EPLIN is a crucial regulator of the interaction
      between normal and transformed epithelial cells.

PMID- 25609712
TI  - Rbfox proteins regulate tissue-specific alternative splicing of Mef2D required
      for muscle differentiation.
AB  - Among the Mef2 family of transcription factors, Mef2D is unique in that it
      undergoes tissue-specific splicing to generate an isoform that is essential for
      muscle differentiation. However, the mechanisms mediating this muscle-specific
      processing of Mef2D remain unknown. Using bioinformatics, we identified Rbfox
      proteins as putative modulators of Mef2D muscle-specific splicing. Accordingly,
      we found direct and specific Rbfox1 and Rbfox2 binding to Mef2D pre-mRNA in vivo.
      Gain- and loss-of-function experiments demonstrated that Rbfox1 and Rbfox2
      cooperate in promoting Mef2D splicing and subsequent myogenesis. Thus, our
      findings reveal a new role for Rbfox proteins in regulating myogenesis through
      activation of essential muscle-specific splicing events.

PMID- 25609713
TI  - The same, only different - DNA damage checkpoints and their reversal throughout
      the cell cycle.
AB  - Cell cycle checkpoints activated by DNA double-strand breaks (DSBs) are essential
      for the maintenance of the genomic integrity of proliferating cells. Following
      DNA damage, cells must detect the break and either transiently block cell cycle
      progression, to allow time for repair, or exit the cell cycle. Reversal of a DNA
      damage-induced checkpoint not only requires the repair of these lesions, but a
      cell must also prevent permanent exit from the cell cycle and actively terminate
      checkpoint signalling to allow cell cycle progression to resume. It is becoming
      increasingly clear that despite the shared mechanisms of DNA damage detection
      throughout the cell cycle, the checkpoint and its reversal are precisely tuned to
      each cell cycle phase. Furthermore, recent findings challenge the dogmatic view
      that complete repair is a precondition for cell cycle resumption. In this
      Commentary, we highlight cell-cycle-dependent differences in checkpoint
      signalling and recovery after a DNA DSB, and summarise the molecular mechanisms
      that underlie the reversal of DNA damage checkpoints, before discussing when and
      how cell fate decisions after a DSB are made. 

PMID- 25609718
TI  - Comparison of the Sofia and Veritor direct antigen detection assay systems for
      identification of influenza viruses from patient nasopharyngeal specimens.
AB  - Influenza antigen detection assays (Sofia fluorescent immunoassay [FIA] and
      Veritor) yield objective results, which are potentially useful for point-of-care
      testing. The assays were evaluated with reverse transcriptase PCR (RT-PCR) using
      411 nasopharyngeal swab specimens. Sensitivity and specificity values
      (percentages) of 79.0/99.0 and 64.0/99.4 for influenza A and 92.9/96.7 and
      78.6/98.7 for influenza B were obtained for the Sofia and Veritor assays,
      respectively. 

PMID- 25609719
TI  - Delineating community outbreaks of Salmonella enterica serovar Typhimurium by use
      of whole-genome sequencing: insights into genomic variability within an outbreak.
AB  - Whole-genome next-generation sequencing (NGS) was used to retrospectively examine
      57 isolates from five epidemiologically confirmed community outbreaks (numbered 1
      to 5) caused by Salmonella enterica serovar Typhimurium phage type DT170. Most of
      the human and environmental isolates confirmed epidemiologically to be involved
      in the outbreaks were either genomically identical or differed by one or two
      single nucleotide polymorphisms (SNPs), with the exception of those in outbreak
      1. The isolates from outbreak 1 differed by up to 12 SNPs, which suggests that
      the food source of the outbreak was contaminated with more than one strain while
      each of the other four outbreaks was caused by a single strain. In addition, NGS
      analysis ruled in isolates that were initially not considered to be linked with
      the outbreak, which increased the total outbreak size by 107%. The mutation
      process was modeled by using known mutation rates to derive a cutoff value for
      the number of SNP difference to determine whether or not a case was part of an
      outbreak. For an outbreak with less than 1 month of ex vivo/in vivo evolution
      time, the maximum number of SNP differences between isolates is two or four using
      the lowest or highest mutation rate, respectively. NGS of S. Typhimurium
      significantly increases the resolution of investigations of community outbreaks.
      It can also inform a more targeted public health response by providing important
      supplementary evidence that cases of disease are or are not associated with food
      borne outbreaks of S. Typhimurium. 

PMID- 25609720
TI  - Detection of Mycobacterium tuberculosis by EasyNAT diagnostic kit in sputum
      samples from Tanzania.
AB  - The EasyNAT assay was evaluated for the detection of tuberculosis in sputum
      smears from presumptive pulmonary tuberculosis (TB) patients in an African high
      TB and high-HIV setting. The sensitivity of the EasyNAT assay was 66.7%, and the
      specificity and positive predictive value were 100% for the culture-positive
      patients. The sensitivity was only 10% in the smear-negative and culture-positive
      patients. 

PMID- 25609721
TI  - Use of the Optum Labs Data Warehouse to assess test ordering patterns for
      diagnosis of Helicobacter pylori infection in the United States.
AB  - We surveyed national Helicobacter pylori diagnostic testing practices and
      diagnoses using commercial and Medicare medical claims data from Optum Labs
      (Cambridge, MA). Serologic testing for antibodies to H. pylori remains the most
      commonly ordered diagnostic test despite recent expert recommendations. Changes
      in reimbursement for serologic testing will likely drive future provider ordering
      practices. 

PMID- 25609722
TI  - Evaluation of a low-density hydrogel microarray technique for mycobacterial
      species identification.
AB  - In addition to the obligatory pathogenic species of the Mycobacterium
      tuberculosis complex and Mycobacterium leprae, the genus Mycobacterium also
      includes conditionally pathogenic species that in rare cases can lead to the
      development of nontuberculous mycobacterial diseases. Because tuberculosis and
      mycobacteriosis have similar clinical signs, the accurate identification of the
      causative agent in a clinical microbiology laboratory is important for diagnostic
      verification and appropriate treatment. This report describes a low-density
      hydrogel-based microarray containing oligonucleotide probes based on the species
      specific sequences of the gyrB gene fragment for mycobacterial species
      identification. The procedure included the amplification of a 352-nucleotide
      fragment of the gene and its hybridization on a microarray. The triple-species
      specific probe design and the algorithm for hybridization profile recognition
      based on the calculation of Pearson correlation coefficients, followed by the
      construction of a profile database, allowed for the reliable and accurate
      identification of mycobacterial species, including mixed-DNA samples. The assay
      was used to evaluate 543 clinical isolates from two regions of Russia,
      demonstrating its ability to detect 35 mycobacterial species, with 99.8%
      sensitivity and 100% specificity when using gyrB, 16S, and internal transcribed
      spacer (ITS) fragment sequencing as the standard. The testing of clinical samples
      showed that the sensitivity of the assay was 89% to 95% for smear-positive
      samples and 36% for smear-negative samples. The large number of identified
      species, the high level of sensitivity, the ability to detect mycobacteria in
      clinical samples, and the up-to-date profile database make the assay suitable for
      use in routine laboratory practice. 

PMID- 25609723
TI  - Foot infection by Clostridium sordellii: case report and review of 15 cases in
      France.
AB  - We report a case of foot infection by Clostridium sordellii and review 15 human
      infections registered at a Reference Center in France during the period 1998 to
      2011. All strains were found nontoxigenic, lacking the lethal toxin gene coding
      for TcsL. Like Clostridium septicum, several C. sordellii infections were
      associated with intestinal neoplasms. 

PMID- 25609724
TI  - Human Diphyllobothrium nihonkaiense infection in Washington State.
AB  - A patient in Washington State harbored a fish tapeworm most likely acquired from
      eating raw salmon. Diphyllobothrium nihonkaiense was identified by cox1 sequence
      analysis. Although this is the first documented human D. nihonkaiense infection
      in the United States, the parasite may have been present earlier but
      misidentified as Diphyllobothrium latum. 

PMID- 25609725
TI  - Efficient, validated method for detection of mycobacterial growth in liquid
      culture media by use of bead beating, magnetic-particle-based nucleic acid
      isolation, and quantitative PCR.
AB  - Pathogenic mycobacteria are difficult to culture, requiring specialized media and
      a long incubation time, and have complex and exceedingly robust cell walls.
      Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's
      disease, a chronic wasting disease of ruminants, is a typical example. Culture of
      MAP from the feces and intestinal tissues is a commonly used test for
      confirmation of infection. Liquid medium offers greater sensitivity than solid
      medium for detection of MAP; however, support for the BD Bactec 460 system
      commonly used for this purpose has been discontinued. We previously developed a
      new liquid culture medium, M7H9C, to replace it, with confirmation of growth
      reliant on PCR. Here, we report an efficient DNA isolation and quantitative PCR
      methodology for the specific detection and confirmation of MAP growth in liquid
      culture media containing egg yolk. The analytical sensitivity was at least 10(4)
      fold higher than a commonly used method involving ethanol precipitation of DNA
      and conventional PCR; this may be partly due to the addition of a bead-beating
      step to manually disrupt the cell wall of the mycobacteria. The limit of
      detection, determined using pure cultures of two different MAP strains, was 100
      to 1,000 MAP organisms/ml. The diagnostic accuracy was confirmed using a panel of
      cattle fecal (n=54) and sheep fecal and tissue (n=90) culture samples. This
      technique is directly relevant for diagnostic laboratories that perform MAP
      cultures but may also be applicable to the detection of other species, including
      M. avium and M. tuberculosis.

PMID- 25609726
TI  - Clinical evaluation of the OneStep Gonorrhea RapiCard InstaTest for detection of
      Neisseria gonorrhoeae in symptomatic patients from KwaZulu-Natal, South Africa.
AB  - We evaluated a point-of-care test for the detection of Neisseria gonorrhoeae in
      patients attending a public health clinic in KwaZulu-Natal, South Africa. The
      test showed a low sensitivity against PCR and culture (<40%); however, a higher
      specificity was observed (>95%). This test is unsuitable as a screening tool for
      gonorrhea. 

PMID- 25609727
TI  - Improving Leishmania species identification in different types of samples from
      cutaneous lesions.
AB  - The discrimination of Leishmania species from patient samples has epidemiological
      and clinical relevance. In this study, different gene target PCR-restriction
      fragment length polymorphism (RFLP) protocols were evaluated for their robustness
      as Leishmania species discriminators in 61 patients with cutaneous leishmaniasis.
      We modified the hsp70-PCR-RFLP protocol and found it to be the most reliable
      protocol for species identification. 

PMID- 25609729
TI  - Evaluation of the Vitros Syphilis TPA chemiluminescence immunoassay as a first
      line method for reverse syphilis screening.
AB  - We report here the results of the diagnostic performances of Vitros Syphilis TPA
      (a chemiluminescence treponemal assay) compared with those of two treponemal
      enzyme immunoassays and of traditional versus reverse syphilis algorithms. Ease
      of use, automation, and high throughput make the Vitros Syphilis TPA assay a good
      choice for syphilis screening in high-volume laboratories. 

PMID- 25609728
TI  - Detection and discrimination of classical and atypical L-type bovine spongiform
      encephalopathy by real-time quaking-induced conversion.
AB  - Statutory surveillance of bovine spongiform encephalopathy (BSE) indicates that
      cattle are susceptible to both classical BSE (C-BSE) and atypical forms of BSE.
      Atypical forms of BSE appear to be sporadic and thus may never be eradicated. A
      major challenge for prion surveillance is the lack of sufficiently practical and
      sensitive tests for routine BSE detection and strain discrimination. The real
      time quaking-induced conversion (RT-QuIC) test, which is based on prion-seeded
      fibrillization of recombinant prion protein (rPrPSen), is known to be highly
      specific and sensitive for the detection of multiple human and animal prion
      diseases but not BSE. Here, we tested brain tissue from cattle affected by C-BSE
      and atypical L-type bovine spongiform encephalopathy (L-type BSE or L-BSE) with
      the RT-QuIC assay and found that both BSE forms can be detected and distinguished
      using particular rPrPSen substrates. Specifically, L-BSE was detected using
      multiple rPrPSen substrates, while C-BSE was much more selective. This substrate
      based approach suggests a diagnostic strategy for specific, sensitive, and rapid
      detection and discrimination of at least some BSE forms.

PMID- 25609730
TI  - Discordance between Xpert MTB/RIF assay and Bactec MGIT 960 Culture System for
      detection of rifampin-resistant Mycobacterium tuberculosis isolates in a country
      with a low tuberculosis (TB) incidence.
AB  - Among 452 samples that were positive by the Xpert MTB/RIF (Xpert) assay and MGIT
      960 system (MGIT), 440 and 10 Mycobacterium tuberculosis samples were detected as
      rifampin susceptible and rifampin resistant, respectively. Two isolates that were
      rifampin susceptible by the MGIT system were rifampin resistant by the Xpert
      assay. rpoB sequencing identified a silent (CTG521TTG) mutation in one isolate
      and a missense (GAC516TAC) mutation in another. The detection of rifampin
      resistance is imperfect with both the Xpert assay and MGIT system. Any discordant
      rifampin resistance results should be confirmed by sequencing of the rpoB gene. 

PMID- 25609731
TI  - Streptococcus gallolyticus subsp. pasteurianus infection in twin infants.
AB  - Streptococcus gallolyticus subsp. pasteurianus, previously known as Streptococcus
      bovis biotype II.2, is an uncommon pathogen in neonates. Nevertheless, it can
      cause severe neonatal sepsis and meningitis often clinically indistinguishable
      from those caused by group B streptococci and has been associated with
      considerable morbidity. We report the first known cases of S. gallolyticus subsp.
      pasteurianus infection in twin infants. 

PMID- 25609732
TI  - A pilot evaluation of external quality assessment of GenoType MTBDRplus versions
      1 and 2 using dried culture spot material.
AB  - Dried culture spots (DCS) of inactivated Mycobacteria strains designed as part of
      an external quality assessment (EQA) program for the GeneXpert system has
      applications to other molecular tuberculosis (TB) diagnostic platforms. DCS
      tested on the GenoType MTBDRplus and Mycobacterium CM assays performed well with
      MTBDRplus version 2 but require increased bacterial concentration for use with
      version 1. 

PMID- 25609733
TI  - Monitoring the quality of HIV-1 viral load testing through a proficiency testing
      program using dried tube specimens in resource-limited settings.
AB  - HIV-1 viral load (VL) levels are used for monitoring disease progression and
      antiretroviral therapy outcomes in HIV-infected patients. To assess the
      performance of laboratories conducting HIV-1 VL testing in resource-limited
      settings, the U.S. Centers for Disease Control and Prevention implemented a
      voluntary, free-of-charge, external quality assurance program using dried tube
      specimens (DTSs). Between 2010 and 2012, DTS proficiency testing (PT) panels
      consisting of 5 specimens were distributed at ambient temperature to
      participants. The results from the participants (n>=6) using the same assay were
      grouped, analyzed, and graded as acceptable within a group mean+/-3 standard
      deviations. Mean proficiency scores were calculated by dividing the combined PT
      scores by the number of testing cycles using a linear regression model. Between
      2010 and 2012, the number of participants enrolled increased from 32 in 16
      countries to 114 in 44 countries. A total of 78.2% of the participants reported
      results using 10 different VL assays. The rates of reporting of acceptable
      results by the participants were 96.6% for the Abbott assay, 96.3% for the Roche
      Cobas assay, 94.5% for the Roche Amplicor assay, 93.0% for the Biocentric assay,
      and 89.3% for the NucliSens assay. The overall mean proficiency scores improved
      over time (P=0.024). DTSs are a good alternative specimen type to plasma
      specimens for VL PT programs, as they do not require cold chain transportation
      and can be used on PCR-based assays. Our data suggest that the CDC HIV-1 VL PT
      program using DTSs positively impacts the testing performance of the
      participants, which might translate into better and more accurate VL testing
      services for patients.

PMID- 25609734
TI  - Effect of N-acetyl-l-cysteine on insulin resistance caused by prolonged free
      fatty acid elevation.
AB  - Circulating free fatty acids (FFAs) are elevated in obesity and cause insulin
      resistance. The objective of the current study was to determine whether the
      antioxidant N-acetyl-l-cysteine (NAC) prevented hepatic and peripheral insulin
      resistance caused by prolonged elevation of plasma FFAs. Chronically cannulated
      Wistar rats received saline (SAL), Intralipid plus heparin (IH), IH plus NAC, or
      NAC i.v. infusion for 48 h. Insulin sensitivity was determined using the
      hyperinsulinemic-euglycemic clamp with tritiated glucose tracer. IH induced
      hepatic and peripheral insulin resistance (P<0.05). NAC co-infusion did not
      prevent insulin resistance in the liver, although it was able to prevent
      peripheral insulin resistance. Prolonged IH infusion did not appear to induce
      oxidative stress in the liver because hepatic content of protein carbonyl,
      malondialdehyde, and reduced to oxidized glutathione ratio did not differ across
      treatment groups. In alignment with our insulin sensitivity results, IH augmented
      skeletal muscle protein carbonyl content and this was prevented by NAC co
      infusion. Taken together, our results indicate that oxidative stress mediates
      peripheral, but not hepatic, insulin resistance resulting from prolonged plasma
      FFA elevation. Thus, in states of chronic plasma FFA elevation, such as obesity,
      antioxidants may protect against peripheral but not hepatic insulin resistance. 

PMID- 25609735
TI  - Effects of atosiban on stress-related neuroendocrine factors.
AB  - Atosiban, an oxytocin/vasopressin receptor antagonist, is used to decrease
      preterm uterine activity. The risk of preterm delivery is undoubtedly associated
      with stress, but potential side effects of atosiban on neuroendocrine functions
      and stress-related pathways are mostly unknown. These studies were designed to
      test the hypothesis that the chronic treatment of rats with atosiban modulates
      neuroendocrine functions under stress conditions. Male rats were treated (osmotic
      minipumps) with atosiban (600 MUg/kg per day) or vehicle and were restrained for
      120 min/day for 14 days. All animals were treated with a marker of cell
      proliferation 5-bromo-2-deoxyuridine. Anxiety-like behavior was measured using an
      elevated plus-maze. Treatment with atosiban failed to modify plasma
      concentrations of the stress hormones ACTH and corticosterone, but led to a rise
      in circulating copeptin. Atosiban increased prolactin levels in the non-stressed
      group. Oxytocin receptor mRNA levels were increased in rats exposed to stress.
      Treatment with atosiban, in both control and stressed animals, resulted in a
      decrease in oxytocin receptor gene expression in the hypothalamus. No changes
      were observed in vasopressin receptor 1A and 1B gene expression. The decrease in
      hippocampal cell proliferation induced by stress exposure was not modified by
      atosiban treatment. This study provides the first data, to our knowledge,
      revealing the effect of atosiban on gene expression of oxytocin receptors in the
      brain. Atosiban-induced enhancement of plasma copeptin indicates an elevation in
      vasopressinergic tone with potential influence on water-electrolyte balance. 

PMID- 25609736
TI  - Diabetic nephropathy is associated with increased urine excretion of proteases
      plasmin, prostasin and urokinase and activation of amiloride-sensitive current in
      collecting duct cells.
AB  - BACKGROUND: Diabetic nephropathy (DN) is associated with hypertension, expanded
      extracellular volume and impaired renal Na(+) excretion. It was hypothesized that
      aberrant glomerular filtration of serine proteases in DN causes proteolytic
      activation of the epithelial sodium channel (ENaC) in the kidney by excision of
      an inhibitory peptide tract from the gamma subunit. METHODS: In a cross-sectional
      design, urine, plasma and clinical data were collected from type 1 diabetic
      patients with DN (n = 19) and matched normoalbuminuric type 1 diabetics
      (controls, n = 20). Urine was examined for proteases by western immunoblotting,
      patch clamp and ELISA. Urine exosomes were isolated to elucidate potential
      cleavage of gammaENaC by a monoclonal antibody directed against the 'inhibitory'
      peptide tract. RESULTS: Compared with control, DN patients displayed
      significantly higher blood pressure and urinary excretion of plasmin(ogen),
      prostasin and urokinase that correlated directly with urine albumin. Western
      blotting confirmed plasmin, prostasin and urokinase in urine from the DN group
      predominantly. Urine from DN evoked a significantly larger amiloride-sensitive
      inward current in single collecting duct cells compared with controls.
      Immunoblotting of urine exosomes showed aquaporin 2 in all patient samples.
      Exosomes displayed a virtual absence of intact gammaENaC while moieties
      compatible with cleavage by furin only, were shown in both groups. Proteolytic
      cleavage by the extracellular serine proteases plasmin or prostasin was observed
      in DN samples predominantly. CONCLUSION: DN is associated with increased urinary
      excretion of plasmin, prostasin and urokinase and proteolytic activation of ENaC
      that might contribute to impaired renal Na(+) excretion and hypertension.

PMID- 25609737
TI  - Vitamin D analogues to target residual proteinuria: potential impact on
      cardiorenal outcomes.
AB  - Residual proteinuria, the amount of proteinuria that remains during optimally
      dosed renin-angiotensin-aldosterone system (RAAS) blockade, is an independent
      risk factor for progressive renal function loss and cardiovascular complications
      in chronic kidney disease (CKD) patients. Dual RAAS blockade may reduce residual
      proteinuria but without translating into improved cardiorenal outcomes at least
      in diabetic nephropathy; rather, dual RAAS blockade may increase the risk of
      adverse events. These findings have challenged the concept of residual
      proteinuria as an absolute treatment target. Therefore, new strategies must be
      explored to address whether by further reduction of residual proteinuria using
      interventions not primarily targeting the RAAS benefit in terms of cardiorenal
      risk reduction would accrue. Both clinical and experimental intervention studies
      have demonstrated that vitamin D can reduce residual proteinuria through both
      RAAS-dependent and RAAS-independent pathways. Future research should
      prospectively explore vitamin D treatment as an adjunct to RAAS blockade in an
      interventional trial exploring clinically relevant cardiorenal end points. 

PMID- 25609738
TI  - Pro-inflammatory cytokines and leukocyte oxidative burst in chronic kidney
      disease: culprits or innocent bystanders?
AB  - BACKGROUND: Pro-inflammatory cytokines are elevated in chronic kidney disease
      (CKD), a condition characterized by microinflammation with oxidative stress as
      key feature. However, their role in the inflammatory response at uraemic
      concentrations has not yet been defined. In this study, the contribution of
      cytokines on induction of leukocyte oxidative stress was investigated. METHODS:
      Whole blood from healthy donors was incubated with 20-1400 pg/mL TNFalpha, 5
      102.8 pg/mL IL-6, 20-400 pg/mL IL-1beta and 75-1200 pg/mL IL-18 separately or in
      combination. Oxidative burst was measured, at baseline and after stimulation with
      fMLP (PhagoburstTM). The effect of the TNFalpha blocker, adalimumab (Ada), was
      evaluated on TNFalpha-induced ROS production. Finally, the association between
      TNFalpha and the composite end point all-cause mortality or first cardiovascular
      event was analysed in a CKD population stage 4-5 (n = 121). RESULTS: While
      interleukin (IL)-6, IL-1beta and IL-18 alone induced no ROS activation of normal
      leukocytes, irrespective of concentrations, TNFalpha induced ROS activation at
      baseline (P < 0.01) and after fMLP stimulation (P < 0.05), but only at uraemic
      concentrations in the high range (400 and 1400 pg/mL). A similar pattern was
      observed with all cytokines in combination, but already at intermediate uraemic
      concentrations (all P < 0.05, except for monocytes after fMLP stimulation: n.s.),
      suggesting synergism between cytokines. ROS production induced by TNFalpha (400
      pg/mL) and the cytokine combination was blocked with Ada. Uraemia-related
      oxidative stress in leukocytes of haemodialysis patients was however not blocked
      by Ada. In patients, TNFalpha was not associated to adverse events (HR: 1.52, 95%
      CI 0.81-2.85, P = 0.13). CONCLUSION: Among several pro-inflammatory cytokines,
      TNFalpha alone was pro-oxidative but only at high-range uraemic concentrations.
      Adding a TNFalpha blocker, Ada, blocked this ROS production, but not the
      oxidative stress in blood samples from haemodialysis patients, suggesting that
      other uraemic toxins than TNFalpha are more crucial in this process. However, the
      lack of association between TNFalpha and mortality suggests that the role of
      TNFalpha-linked oxidative stress is limited.

PMID- 25609739
TI  - Maintenance therapy in antineutrophil cytoplasmic antibody-associated vasculitis:
      who needs what and for how long?
AB  - Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are
      severe chronic auto-immune diseases in which the small vessels are inflamed.
      Nowadays, in the majority of patients disease can be brought into remission with
      cyclophosphamide and corticosteroids. However, depending upon disease
      characteristics patients with AAV have a risk of 29-60% to experience relapses of
      disease within 5 years despite maintenance therapy after induction of remission
      with less toxic agents, such as azathioprine, methotrexate or mycophenolate
      mofetil. More recently, rituximab has been found effective in both induction and
      maintenance of remission in AAV. This review discusses the different aspects of
      maintenance therapy in AAV based on reported cohorts and studies, including the
      different agents, therapy duration, efficacy or lack thereof and future
      directions. Finally, recommendations are made who to treat and for how long. 

PMID- 25609740
TI  - Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic
      analysis of a two-centre cohort.
AB  - BACKGROUND: Patients with anti-glomerular basement membrane (GBM) disease are at
      increased risk of morbidity and mortality from renal failure, pulmonary
      haemorrhage or complications of treatment. One-third also have circulating anti
      neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine
      the clinicopathologic predictors of patient and renal outcomes in anti-GBM
      disease with or without ANCA. METHODS: Retrospective review of 43 patients
      diagnosed with anti-GBM disease over 20 years in two centres, including nine with
      dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored
      for the presence of active and chronic lesions. RESULTS: Dual-positive patients
      were almost 20 years older than those with anti-GBM positivity alone (P = 0.003).
      The overall 1-year patient and renal survivals were 88 and 16%, respectively.
      Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16
      patients without oligoanuria died. In a Cox regression model excluding
      oligoanuria, age was the only other independent predictor of survival. Pulmonary
      haemorrhage and dialysis dependence did not influence mortality. Thirty-five of
      the forty-three (81%) patients required dialysis at presentation, including all
      nine dual-positive patients. Of them, only two (5.7%) regained renal function at
      1 year. By logistic regression, oligoanuria at diagnosis and percentage of
      crescents were independent predictors of dialysis independence at 3 months.
      However, in biopsied patients, the presence of crescents (>75%) added little to
      the presence of oligoanuria in predicting dialysis independence. Histological
      activity and chronicity indices did not predict renal outcome. Two of the nine
      (22%) dual-positive patients relapsed compared with none of the anti-GBM alone
      patients. Seven patients received kidney transplants without disease recurrence.
      CONCLUSIONS: Oligoanuria is the strongest predictor of patient and renal survival
      while percentage of glomerular crescents is the only pathologic parameter
      associated with poor renal outcome in anti-GBM disease. Kidney biopsy may not be
      necessary in oligoanuric patients without pulmonary haemorrhage.

PMID- 25609741
TI  - Dose-volume histogram comparison between static 5-field IMRT with 18-MV X-rays
      and helical tomotherapy with 6-MV X-rays.
AB  - We treated prostate cancer patients with static 5-field intensity-modulated
      radiation therapy (IMRT) using linac 18-MV X-rays or tomotherapy with 6-MV X
      rays. As X-ray energies differ, we hypothesized that 18-MV photon IMRT may be
      better for large patients and tomotherapy may be more suitable for small
      patients. Thus, we compared dose-volume parameters for the planning target volume
      (PTV) and organs at risk (OARs) in 59 patients with T1-3 N0M0 prostate cancer who
      had been treated using 5-field IMRT. For these same patients, tomotherapy plans
      were also prepared for comparison. In addition, plans of 18 patients who were
      actually treated with tomotherapy were analyzed. The evaluated parameters were
      homogeneity indicies and a conformity index for the PTVs, and D2 (dose received
      by 2% of the PTV in Gy), D98, Dmean and V10-70 Gy (%) for OARs. To evaluate
      differences by body size, patients with a known body mass index were grouped by
      that index ( <21; 21-25; and >25 kg/m(2)). For the PTV, all parameters were
      higher in the tomotherapy plans compared with the 5-field IMRT plans. For the
      rectum, V10 Gy and V60 Gy were higher, whereas V20 Gy and V30 Gy were lower in
      the tomotherapy plans. For the bladder, all parameters were higher in the
      tomotherapy plans. However, both plans were considered clinically acceptable.
      Similar trends were observed in 18 patients treated with tomotherapy. Obvious
      trends were not observed for body size. Tomotherapy provides equivalent dose
      distributions for PTVs and OARs compared with 18-MV 5-field IMRT. Tomotherapy
      could be used as a substitute for high-energy photon IMRT for prostate cancer
      regardless of body size. 

PMID- 25609750
TI  - Injury Prevention at 20.

PMID- 25609749
TI  - Abnormal cartilage development and altered N-glycosylation in Tmem165-deficient
      zebrafish mirrors the phenotypes associated with TMEM165-CDG.
AB  - The congenital disorders of glycosylation (CDG), a group of inherited diseases
      characterized by aberrant glycosylation, encompass a wide range of defects,
      including glycosyltransferases, glycosidases, nucleotide-sugar transporters as
      well as proteins involved in maintaining Golgi architecture, pH and vesicular
      trafficking. Mutations in a previously undescribed protein, TMEM165, were
      recently shown to cause a new form of CDG, termed TMEM165-CDG. TMEM165-CDG
      patients exhibit cartilage and bone dysplasia and altered glycosylation of serum
      glycoproteins. We utilized a morpholino knockdown strategy in zebrafish to
      investigate the physiologic and pathogenic functions of TMEM165. Inhibition of
      tmem165 expression in developing zebrafish embryos caused craniofacial
      abnormalities, largely attributable to fewer chondrocytes. Decreased expression
      of several markers of cartilage and bone development suggests that Tmem165
      deficiency alters both chondrocyte and osteoblast differentiation. Glycomic
      analysis of tmem165 morphants also revealed altered initiation, processing and
      extension of N-glycans, paralleling some of the glycosylation changes noted in
      human patients. Collectively, these findings highlight the utility of zebrafish
      to elucidate pathogenic mechanisms associated with glycosylation disorders and
      suggest that the cartilage and bone dysplasia manifested in TMEM165-CDG patients
      may stem from abnormal development of chondrocytes and osteoblasts. 

PMID- 25609751
TI  - How it all began: from conception to birth to early adulthood.

PMID- 25609748
TI  - A genome-wide association study of resistance to stripe rust (Puccinia
      striiformis f. sp. tritici) in a worldwide collection of hexaploid spring wheat
      (Triticum aestivum L.).
AB  - New races of Puccinia striiformis f. sp. tritici (Pst), the causal pathogen of
      wheat stripe rust, show high virulence to previously deployed resistance genes
      and are responsible for large yield losses worldwide. To identify new sources of
      resistance we performed a genome-wide association study (GWAS) using a worldwide
      collection of 1000 spring wheat accessions. Adult plants were evaluated under
      field conditions in six environments in the western United States, and seedlings
      were tested with four Pst races. A single-nucleotide polymorphism (SNP) Infinium
      9K-assay provided 4585 SNPs suitable for GWAS. High correlations among
      environments and high heritabilities were observed for stripe rust infection type
      and severity. Greater levels of Pst resistance were observed in a subpopulation
      from Southern Asia than in other groups. GWAS identified 97 loci that were
      significant for at least three environments, including 10 with an experiment-wise
      adjusted Bonferroni probability < 0.10. These 10 quantitative trait loci (QTL)
      explained 15% of the phenotypic variation in infection type, a percentage that
      increased to 45% when all QTL were considered. Three of these 10 QTL were mapped
      far from previously identified Pst resistance genes and QTL, and likely represent
      new resistance loci. The other seven QTL mapped close to known resistance genes
      and allelism tests will be required to test their relationships. In summary, this
      study provides an integrated view of stripe rust resistance resources in spring
      wheat and identifies new resistance loci that will be useful to diversify the
      current set of resistance genes deployed to control this devastating disease. 

PMID- 25609752
TI  - Epidemiology of bicycle injuries and risk factors for serious injury. 1997.
AB  - OBJECTIVE: To determine the risk factors for serious injury to bicyclists, aside
      from helmet use. DESIGN: Prospective case-control study. SETTING: Seven Seattle
      area hospital emergency departments and two county medical examiner's offices.
      PATIENTS: Individuals treated in the emergency department or dying from bicycle
      related injuries. MEASUREMENTS: Information collected from injured bicyclists or
      their parents by questionnaire on circumstances of the crash; abstract of medical
      records for injury data. Serious injury defined as an injury severity score>8.
      ANALYSIS: Odd ratios computed using the maximum likelihood method, and adjusted
      using unconditional logistic regression. RESULTS: There were 3854 injured
      cyclists in the three year period; 3390 (88%) completed questionnaires were
      returned. 51% wore helmets at the time of crash. Only 22.3% of patients had head
      injuries and 34% had facial injuries. Risk of serious injury was increased by
      collision with a motor vehicle (odds ratio (OR)=4.6), self reported speed >15 mph
      (OR=1.2), young age (<6 years), and age >39 years (OR=2.1 and 2.2 respectively,
      compared with adults 20-39 years). Risk for serious injury was not affected by
      helmet use (OR=0.9). Risk of neck injury was increased in those struck by motor
      vehicles (OR=4.0), hospitalized for any injury (OR=2.0), and those who died
      (OR=15.1), but neck injury was not affected by helmet use. CONCLUSIONS:
      Prevention of serious bicycle injuries cannot be accomplished through helmet use
      alone, and may require separation of cyclists from motor vehicles, and delaying
      cycling until children are developmentally ready.

PMID- 25609755
TI  - Correction.

PMID- 25609753
TI  - Building the evidence base for safe and active bicycling: an historical
      commentary on Rivara et al: epidemiology of bicycle injuries and risk factors for
      serious injury.

PMID- 25609756
TI  - Noma: neglected, forgotten and a human rights issue.
AB  - Noma, an orofacial gangrene and opportunistic infection, affects primarily
      malnourished children living in extreme poverty. Neglected, forgotten, unknown by
      most health workers, noma results in death, disfigurement and disability of some
      of the world's most vulnerable children. Noma is a biological indicator of
      multiple human rights violations, including the right to food. International
      support and national attention in countries with noma are lacking. The end of
      neglect of noma can lead to the elimination of this horrific childhood disease. 

PMID- 25609757
TI  - Ineffective acute treatment of episodic migraine is associated with new-onset
      chronic migraine.
AB  - OBJECTIVE: To test the hypothesis that ineffective acute treatment of episodic
      migraine (EM) is associated with an increased risk for the subsequent onset of
      chronic migraine (CM). METHODS: In the American Migraine Prevalence and
      Prevention Study, respondents with EM in 2006 who completed the Migraine
      Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007
      were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses
      treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ
      4 scores were used to define categories of acute treatment response: very poor,
      poor, moderate, and maximum treatment efficacy. Logistic regression models were
      used to examine the dichotomous outcome of transition from EM in 2006 to CM in
      2007 as a function of mTOQ-4 category, adjusting for covariates. RESULTS: Among
      5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007.
      Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new
      onset CM increased in the moderate treatment efficacy (2.7%), poor treatment
      efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully
      adjusted model, the very poor treatment efficacy group had a more than 2-fold
      increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42
      4.61) compared to the maximum treatment efficacy group. CONCLUSION: Inadequate
      acute treatment efficacy was associated with an increased risk of new-onset CM
      over the course of 1 year. Improving acute treatment outcomes might prevent new
      onset CM, although reverse causality cannot be excluded.

PMID- 25609759
TI  - Effectiveness in acute migraine treatment: how it might matter.

PMID- 25609758
TI  - Olfactory dysfunction predicts early transition to a Lewy body disease in
      idiopathic RBD.
AB  - OBJECTIVE: The aim of the present study was to determine the predictive value of
      olfactory dysfunction for the early development of a synuclein-mediated
      neurodegenerative disease in subjects with idiopathic REM sleep behavior disorder
      (iRBD) over an observational period of 5 years. METHODS: Thirty-four patients
      with polysomnography-confirmed iRBD underwent olfactory testing using the entire
      Sniffin' Sticks test assessing odor identification, odor discrimination, and
      olfactory threshold. Patients with iRBD were prospectively followed up over a
      period of 4.9 +/- 0.3 years (mean +/- SD). The diagnosis of neurodegenerative
      diseases was based on current clinical diagnostic criteria. RESULTS: After 2.4 +/
      1.7 years (mean +/- SD), 9 patients (26.5%) with iRBD developed a Lewy body
      disease (6 Parkinson disease and 3 dementia with Lewy bodies). The entire
      Sniffin' Sticks test and the identification subtest had the same overall
      diagnostic accuracy of 82.4% (95% confidence interval: 66.1%-92.0%) in predicting
      conversion. The relative risk for a Lewy body disease in the lowest tertile of
      olfactory function was 7.3 (95% confidence interval: 1.8-29.6) compared with the
      top 2 tertiles. CONCLUSIONS: Assessment of olfactory function, particularly odor
      identification, may help to predict the development of a Lewy body disease in
      patients with iRBD over a relatively short time period and thus to identify
      patients suitable for future disease modification trials.

PMID- 25609760
TI  - Development and validation of risk index for cognitive decline using blood
      derived markers.
AB  - OBJECTIVE: We sought to develop and validate a risk index for prospective
      cognitive decline in older adults based on blood-derived markers. METHODS: The
      index was based on 8 markers that have been previously associated with cognitive
      aging: APOE genotype, plasma beta-amyloid 42/40 ratio, telomere length, cystatin
      C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was
      person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11
      years of follow-up. A total of 1,445 older adults comprised the development
      sample. An index based on dichotomized markers was divided into low-, medium-,
      and high-risk categories; the risk categories were validated with the remaining
      sample (n = 739) using linear regression. Amyloid was measured on a subsample (n
      = 865) and was included only in a secondary index. RESULTS: The risk categories
      showed significant differences from each other and were predictive of prospective
      cognitive decline in the validation sample, even after adjustment for age and
      baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95%
      confidence interval [CI]: -0.46, -0.19), the medium-risk group (58.7%) declined
      0.55 points/y (95% CI: -0.65, 0.45), and the high-risk group (16.6%) declined
      0.69 points/y (95% CI: -0.85, -0.54). Using the secondary index, which included
      beta-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20
      points/y (95% CI: -0.42, 0.01), the medium-risk group (61.3%) declined 0.55
      points/y (95% CI: -0.72, -0.38), and the high-risk group (11.8%) declined 0.83
      points/y (95% CI: -1.14, -0.51). CONCLUSIONS: A risk index based on 8 blood-based
      markers was modestly able to predict cognitive decline over an 11-year follow-up.
      Further validation in other cohorts is necessary.

PMID- 25609761
TI  - The effects of test-enhanced learning on long-term retention in AAN annual
      meeting courses.
AB  - OBJECTIVE: We measured the long-term retention of knowledge gained through
      selected American Academy of Neurology annual meeting courses and compared the
      effects of repeated quizzing (known as test-enhanced learning) and repeated
      studying on that retention. METHODS: Participants were recruited from 4 annual
      meeting courses. All participants took a pretest. This randomized, controlled
      trial utilized a within-subjects design in which each participant experienced 3
      different postcourse activities with each activity performed on different
      material. Each key information point from the course was randomized in a
      counterbalanced fashion among participants to one of the 3 activities: repeated
      short-answer quizzing, repeated studying, and no further exposure to the
      materials. A final test covering all information points from the course was taken
      5.5 months after the course. RESULTS: Thirty-five participants across the 4
      courses completed the study. Average score on the pretest was 36%. Performance on
      the final test showed that repeated quizzing led to significantly greater long
      term retention relative to both repeated studying (55% vs 46%; t[34] = 3.28, SEM
      = 0.03, p = 0.01, d = 0.49) and no further exposure (55% vs 44%; t[34] = 3.16,
      SEM = 0.03, p = 0.01, d = 0.58). Relative to the pretest baseline, repeated
      quizzing helped participants to retain almost twice as much of the knowledge
      acquired from the course compared to repeated studying or no further exposure.
      CONCLUSIONS: Whereas annual meeting continuing medical education (CME) courses
      lead to long-term gains in knowledge, when repeated quizzing is added, retention
      is significantly increased. CME planners may consider adding repeated quizzing to
      increase the impact of their courses.

PMID- 25609762
TI  - Pulvinar: associative role in cortical function and clinical correlations.

PMID- 25609764
TI  - Association of prone position with sudden unexpected death in epilepsy.
AB  - OBJECTIVE: To examine the association between prone position and sudden
      unexpected death in epilepsy (SUDEP). METHODS: We conducted a systematic review
      and meta-analysis based on a literature search from databases PubMed, Web of
      Science, and Scopus, using keywords "SUDEP" or "sudden unexpected death in
      epilepsy" or "sudden unexplained death syndromes in epilepsy." Twenty-five
      publications met the inclusion and exclusion criteria and were enrolled in this
      study. RESULTS: Body positions were documented in 253 cases of SUDEP. Of these
      patients, 73.3% (95% confidence interval [CI] = 65.7%, 80.9%) died in the prone
      position, whereas 26.7% (95% CI = 16.3%, 37.1%) died in nonprone positions.
      Binary random-effects analysis showed that prone position is significantly
      associated with SUDEP, as compared with nonprone position (p < 0.001). In
      addition, the prone position was reported in all 11 cases of video-EEG-monitored
      SUDEP. Moreover, in a subgroup of 88 cases of SUDEP in which demographics and
      circumstances of death were documented, the prone position was observed in 85.7%
      (95% CI = 74.6%, 93.3%) of patients aged 40 years or younger, but in only 60%
      (95% CI = 38.7%, 78.9%) of patients older than 40 years. Statistical analysis
      confirmed that the prone position was significantly more prevalent in the younger
      patient group, as compared with the older patient group (odds ratio 3.9; 95% CI =
      1.4%, 11.4%; p = 0.009). CONCLUSION: There is a significant association between
      prone position and SUDEP, which suggests that prone position is a major risk
      factor for SUDEP, particularly in patients aged 40 years and younger. As such,
      SUDEP may share mechanisms similar to sudden infant death syndrome.

PMID- 25609765
TI  - Facing up to SUDEP.

PMID- 25609763
TI  - Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal
      muscular atrophy.
AB  - OBJECTIVE: To expand the clinical phenotype of autosomal dominant congenital
      spinal muscular atrophy with lower extremity predominance (SMA-LED) due to
      mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS:
      Patients with a phenotype suggestive of a motor, non-length-dependent
      neuronopathy predominantly affecting the lower limbs were identified at
      participating neuromuscular centers and referred for targeted sequencing of
      DYNC1H1. RESULTS: We report a cohort of 30 cases of SMA-LED from 16 families,
      carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel
      mutations. These patients are characterized by congenital or childhood-onset
      lower limb wasting and weakness frequently associated with cognitive impairment.
      The clinical severity is variable, ranging from generalized arthrogryposis and
      inability to ambulate to exclusive and mild lower limb weakness. In many
      individuals with cognitive impairment (9/30 had cognitive impairment) who
      underwent brain MRI, there was an underlying structural malformation resulting in
      polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern
      suggestive of denervation characterized by sparing and relative hypertrophy of
      the adductor longus and semitendinosus muscles at the thigh level, and diffuse
      involvement with relative sparing of the anterior-medial muscles at the calf
      level. Proximal muscle histopathology did not always show classic neurogenic
      features. CONCLUSION: Our report expands the clinical spectrum of DYNC1H1-related
      SMA-LED to include generalized arthrogryposis. In addition, we report that the
      neurogenic peripheral pathology and the CNS neuronal migration defects are often
      associated, reinforcing the importance of DYNC1H1 in both central and peripheral
      neuronal functions.

PMID- 25609766
TI  - Relationships between quantitative spinal cord MRI and retinal layers in multiple
      sclerosis.
AB  - OBJECTIVE: To assess relationships between spinal cord MRI (SC-MRI) and retinal
      measures, and to evaluate whether these measures independently relate to clinical
      disability in multiple sclerosis (MS). METHODS: One hundred two patients with MS
      and 11 healthy controls underwent 3-tesla brain and cervical SC-MRI, which
      included standard T1- and T2-based sequences and diffusion-tensor and
      magnetization-transfer imaging, and optical coherence tomography with automated
      segmentation. Clinical assessments included visual acuity (VA), Expanded
      Disability Status Scale, MS functional composite, vibration sensation threshold,
      and hip-flexion strength. Regions of interest circumscribing SC cross-sections at
      C3-4 were used to obtain cross-sectional area (CSA), fractional anisotropy (FA),
      perpendicular diffusivity (lambda?), and magnetization transfer ratio.
      Multivariable regression assessed group differences and SC, retinal, and clinical
      relationships. RESULTS: In MS, there were correlations between SC-CSA, SC-FA, SC
      lambda?, and peripapillary retinal nerve fiber layer (pRNFL) (p = 0.01, p =
      0.002, p = 0.001, respectively) after adjusting for age, sex, prior optic
      neuritis, and brain atrophy. In multivariable clinical models, when SC-CSA,
      pRNFL, and brain atrophy were included simultaneously, SC-CSA and pRNFL retained
      independent relationships with low-contrast VA (p = 0.04, p = 0.002,
      respectively), high-contrast VA (p = 0.06, p = 0.008), and vibration sensation
      threshold (p = 0.01, p = 0.05). SC-CSA alone retained independent relationships
      with Expanded Disability Status Scale (p = 0.001), hip-flexion strength (p =
      0.001), and MS functional composite (p = 0.004). CONCLUSIONS: In this cross
      sectional study of patients with MS, correlations exist between SC-MRI and
      retinal layers, and both exhibit independent relationships with clinical
      dysfunction. These findings suggest that the SC and optic nerve reflect ongoing
      global pathologic processes that supplement measures of whole-brain atrophy,
      highlighting the importance of combining measures from unique compartments to
      facilitate a thorough examination of regional and global disease processes that
      contribute to clinical disability in MS.

PMID- 25609768
TI  - Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia.
AB  - OBJECTIVE: To present the clinical, molecular, and cell biological findings in a
      family with an autosomal recessive form of hereditary spastic paraplegia
      characterized by a combination of spastic paraplegia, optic atrophy, and
      peripheral neuropathy (SPOAN). METHODS: We used a combination of whole-genome
      linkage analysis and exome sequencing to map the disease locus and to identify
      the responsible gene. To analyze the physiologic consequences of the disease, we
      used biochemical and cell biological methods. RESULTS: Ten members of a highly
      consanguineous family manifested a childhood-onset SPOAN-like phenotype with slow
      progression into late adulthood. We mapped this disorder to a locus on chromosome
      1q and identified a homozygous donor splice-site mutation in the IBA57 gene,
      previously implicated in 2 infants with lethal perinatal encephalomyopathy. This
      gene encodes the mitochondrial iron-sulfur (Fe/S) protein assembly factor IBA57.
      In addition to a severely decreased amount of normal IBA57 messenger RNA, a
      patient's cells expressed an aberrantly spliced messenger RNA with a premature
      stop codon. Lymphoblasts contained 10-fold-lower levels of wild-type, but no
      signs of truncated IBA57 protein. The decrease in functional IBA57 resulted in
      reduced levels and activities of several mitochondrial [4Fe-4S] proteins,
      including complexes I and II, while mitochondrial [2Fe-2S] proteins remained
      normal. CONCLUSIONS: Our findings reinforce the suggested specific function of
      IBA57 in mitochondrial [4Fe-4S] protein maturation and provide additional
      evidence for its role in human disease. The less decreased IBA57 protein level in
      this family explains phenotypic differences compared with the previously
      described lethal encephalomyopathy with no functional IBA57.

PMID- 25609770
TI  - Imaging and prevention.

PMID- 25609769
TI  - Biological tumor volume in 18FET-PET before radiochemotherapy correlates with
      survival in GBM.
AB  - OBJECTIVE: The aim of this prospective longitudinal study was to identify static
      and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine PET ((18)FET-PET)-derived imaging
      biomarkers in patients with glioblastoma (GBM). METHODS: Seventy-nine patients
      with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy
      (unresectable tumors) and 37 patients microsurgical tumor resection. All patients
      were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide
      (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done
      before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3
      cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic
      factors were obtained from proportional hazards models. RESULTS: Biological tumor
      volume before RCx (BTV(preRCx)) was the most important (18)FET-PET-derived
      imaging biomarker and was independent of MGMT promoter methylation and clinical
      prognostic factors: patients with smaller BTV(preRCx) had significantly longer
      progression-free and overall survival (OS). (18)FET time-activity curves (TACs)
      before treatment and their changes after RCx were also related to outcome;
      patients with initially increasing TACs experienced longer OS. CONCLUSION:
      BTV(preRCx) and TAC represent important (18)FET-PET-derived imaging biomarkers in
      GBM. Increasing TACs are associated with prolonged OS. The BTV(preRCx) is a
      strong prognostic factor for progression-free survival and OS independent of the
      mode of surgery. Our data furthermore suggest that patients harboring resectable
      GBM might benefit from maximal PET-guided tumor resection.

PMID- 25609771
TI  - Profile: Marc A. Pfeffer, MD PhD.

PMID- 25609773
TI  - Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients
      during continuous-flow left ventricular assist device support.
AB  - OBJECTIVES: During support with a left ventricular assist device (LVAD), partial
      reverse remodelling takes place in which fibrosis plays an important role. In
      this study, we analysed the histological changes and expression of fibrotic
      markers in patients with advanced heart failure (HF) during continuous-flow LVAD
      (cf-LVAD) support. METHODS: In 25 patients, myocardial tissue at the time of LVAD
      implantation (pre-LVAD) was compared with tissue from the explanted left
      ventricle (post-LVAD). Interstitial fibrosis and cardiomyocyte size were analysed
      pre- and post-LVAD. Plasma was obtained from all patients before and during LVAD
      support. Plasma levels, cardiac mRNA and protein expression of brain natriuretic
      peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF),
      osteopontin (OPN) and transforming growth factor beta-1 were determined. RESULTS:
      Fibrosis increased during cf-LVAD unloading (P < 0.05). Cardiomyocytes elongated
      (P < 0.05), whereas cross-sectional area did not change. BNP, Gal-3, CTGF and OPN
      were significantly elevated pre-LVAD in comparison with controls. BNP decreased
      significantly after 1 month of cf-LVAD support (P < 0.001) to near-normal levels.
      Pro-fibrotic markers remained elevated in comparison with controls. CONCLUSIONS:
      cf-LVAD support is associated with lengthening of cardiomyocytes, without
      alterations in diameter size. Remarkably, myocardial fibrosis increased as well
      as circulating pro-fibrotic markers. Whether the morphological changes are a
      direct effect of reduced pulsatility during cf-LVAD support or due to HF
      progression requires further investigation.

PMID- 25609772
TI  - Lymphocytes in atherosclerosis.

PMID- 25609774
TI  - Frequency of ambulatory care adverse events in Latin American countries: the
      AMBEAS/PAHO cohort study.
AB  - OBJECTIVE: Determine the frequency and preventability of adverse events (AEs)
      from available information sources in selected ambulatory care (AC) sites in
      Latin America (LA). DESIGN: Multinational observational cohort was conducted to
      determine the period prevalence (retrospective focus) and the cumulative
      incidence (prospective focus) of AEs. SETTING: Outpatient clinics in Mexico,
      Peru, Brazil and Colombia. PARTICIPANTS: A random selection of 2080 patients.
      INTERVENTIONS: The existence of AE was decided based on trigger information
      provided by the patient and crossing the data with each patient's medical
      history. MAIN OUTCOME MEASURES: AE occurrences 6 months prior (prevalence) and 42
      days after (incidence) the patient receiving AC were identified. AE type and
      preventability were also described. RESULTS: Two thousand eighty patients
      participated in the study. AEs prevalence was 5.2% (108/2080) [95% confidence
      interval (CI) 4.2-6.1%], and cumulative incidence was 2.4% (42/1757) (95% CI 1.7
      3.1%). AEs considered preventable were 44% (55/108) of prevalence period, and
      52.4% (22/42) of incidence period. Preventability was associated with patient
      socioeconomic status (OR 3.5, 95% CI 1.4-8.8), medication error (OR 0.1, 95% CI
      0.0-0.4), diagnostic error (OR 0.1, 95% CI 0.0-0.8) and a minor impact on the
      patient (OR 0.2 95% CI 0.1-0.9). CONCLUSION: The frequency of AE in ambulatory
      settings in LA is in the high-frequency range of research focused on the
      prevalence of AEs. Fifty percent was preventable. This study provides an approach
      for assessing the frequency and preventability of AE in order to enhance patient
      safety in LA.

PMID- 25609775
TI  - A feasibility study of the provision of a personalized interdisciplinary
      audiovisual summary to facilitate care transfer care at hospital discharge: Care
      Transfer Video (CareTV).
AB  - OBJECTIVE: To assess the feasibility and patient acceptance of a personalized
      interdisciplinary audiovisual record to facilitate effective communication with
      patients, family, carers and other healthcare workers at hospital discharge.
      DESIGN: Descriptive pilot study utilizing a study-specific patient feedback
      questionnaire conducted from October 2013 to June 2014. SETTING AND PARTICIPANTS:
      Twenty General Medical inpatients being discharged from an Acute General Medical
      Ward in a metropolitan teaching hospital. INTERVENTION: Audiovisual record of a
      CareTV filmed at the patient's bedside by a consultant-led interdisciplinary
      team, within 24 h prior to discharge from the ward, provided immediately for the
      patient to take home. Patient surveys were completed within 2 weeks of discharge.
      MAIN OUTCOME MEASURES: Technical quality, utilization, acceptability, patient
      satisfaction and recall of diagnosis, medication changes and post-discharge
      review arrangements. RESULTS: All patients had watched their CareTV either alone
      or in the presence of a variety of others: close family, their GP, a medical
      specialist, friends or other health personnel. Participating patients had good
      understanding of the video content and recall of their diagnosis, medication
      changes and post-discharge plans. Patient feedback was overwhelmingly positive.
      CONCLUSIONS: In the context of a General Medical Unit with extensive experience
      in interdisciplinary bedside rounding and teamwork, CareTV is simple to
      implement, inexpensive, technically feasible, requires minimal staff training and
      is acceptable to patients. The results of this pilot study will inform and
      indicate the feasibility of conducting a larger randomized control trial of the
      impact of CareTV on patient satisfaction, medication adherence and recall of key
      information, and primary healthcare provider satisfaction.

PMID- 25609767
TI  - Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood
      protein measures.
AB  - BACKGROUND: The goal of this study was to identify a clinical biomarker signature
      of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1)
      mild cognitive impairment (MCI) cohort. METHODS: We developed a multimodal
      biomarker classifier for predicting brain amyloidosis using cognitive, imaging,
      and peripheral blood protein ADNI1 MCI data. We used CSF beta-amyloid 1-42
      (Abeta42) <= 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET
      standard uptake value ratio >= 1.5. We trained our classifier in the subcohort
      with CSF Abeta42 but no PiB-PET data and tested its performance in the subcohort
      with PiB-PET but no CSF Abeta42 data. We also examined the utility of our
      biomarker signature for predicting disease progression from MCI to Alzheimer
      dementia. RESULTS: The CSF training classifier selected Mini-Mental State
      Examination, Trails B, Auditory Verbal Learning Test delayed recall, education,
      APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved
      leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing
      classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed,
      AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and
      accuracy = 71%. CONCLUSIONS: Automated classifiers based on cognitive and
      peripheral blood protein variables can identify the presence of brain amyloidosis
      with a modest level of accuracy. Such methods could have implications for
      clinical trial design and enrollment in the near future. CLASSIFICATION OF
      EVIDENCE: This study provides Class II evidence that a classification algorithm
      based on cognitive, imaging, and peripheral blood protein measures identifies
      patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%,
      specificity 78%).

PMID- 25609776
TI  - Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack
      of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours.
AB  - OBJECTIVE: Testicular adrenal rest tumours (TARTs) are a common finding in
      patients with congenital adrenal hyperplasia (CAH). These tumours constitute a
      diagnostic and management conundrum and may lead to infertility. TART cells share
      many functional and morphological similarities with Leydig cells (LCs), and
      masses consisting of such cells are occasionally misclassified as malignant
      testicular tumours, which may lead to erroneous orchiectomy in these patients.
      DESIGN: In this study, we aimed to investigate the potential of LC developmental
      markers and adrenal steroidogenic markers in the differential diagnosis of TARTs
      and malignant LC tumours (LCTs). METHODS: We investigated mRNA and protein
      expression of testicular steroidogenic enzymes; CYP11A1 and HSD3B1/2, markers of
      adrenal steroidogenesis; CYP11B1, CYP21A2 and ACTH receptor/melanocortin 2
      receptor (MC2R), and markers of LC maturation; and delta-like 1 homolog (DLK1)
      and insulin-like 3 (INSL3) in testicular biopsies with TART, orchiectomy
      specimens with LCTs and samples from human fetal adrenals. RESULTS: Expression of
      testicular steroidogenic enzymes was observed in all specimens. All investigated
      adrenal steroidogenic markers were expressed in TART, and weak reactions for
      CYP11B1 and MC2R were observed at the protein level in LTCs. TART and fetal
      adrenals had identical expression profiles. DLK1 was highly expressed and INSL3
      not detectable in TART, whereas INSL3 was highly expressed in LCTs. CONCLUSIONS:
      The similar expression profiles in TART and fetal adrenals as well as the
      presence of classical markers of adrenal steroidogenesis lend support to the
      hypothesis that TART develops from a displaced adrenal cell type. Malignant LCTs
      seem to have lost DLK1 expression and do not resemble immature LCs. The different
      expression pattern of DLK1, INSL3 and most adrenocortical markers adds to the
      elucidation of the histogenesis of testicular interstitial tumours and may
      facilitate histopathological diagnosis.

PMID- 25609778
TI  - Hand-held ultrasound-the real stethoscope.

PMID- 25609777
TI  - Screening for ACTH-dependent hypercortisolism in patients with pituitary
      incidentaloma.

PMID- 25609779
TI  - Temporal patterning of thermal acclimation: from behavior to membrane biophysics.

PMID- 25609780
TI  - Transient-state mechanisms of wind-induced burrow ventilation.
AB  - Burrows are common animal habitations, yet living in a burrow presents
      physiological challenges for its inhabitants because the burrow isolates them
      from sources and sinks for oxygen, carbon dioxide, water vapor and ammonia.
      Conventionally, the isolation is thought to be overcome by either diffusion gas
      exchange within the burrow or some means of capturing wind energy to power steady
      or quasi-steady bulk flows of air through it. Both are examples of what may be
      called 'DC' models, namely steady to quasi-steady flows powered by steady to
      quasi-steady winds. Natural winds, however, are neither steady nor quasi-steady,
      but are turbulent, with a considerable portion of the energy contained in so
      called 'AC' (i.e. unsteady) components, where wind velocity varies chaotically
      and energy to power gas exchange is stored in some form. Existing DC models of
      burrow gas exchange do not account for this potentially significant source of
      energy for ventilation. We present evidence that at least two AC mechanisms
      operate to ventilate both single-opening burrows (of the Cape skink, Trachylepis
      capensis) and double-opening model burrows (of Sundevall's jird, Meriones
      crassus). We propose that consideration of the physiological ecology and
      evolution of the burrowing habit has been blinkered by the long neglect of AC
      ventilation. 

PMID- 25609781
TI  - The biomechanics of burrowing and boring.
AB  - Burrowers and borers are ecosystem engineers that alter their physical
      environments through bioturbation, bioirrigation and bioerosion. The mechanisms
      of moving through solid substrata by burrowing or boring depend on the mechanical
      properties of the medium and the size and morphology of the organism. For
      burrowing animals, mud differs mechanically from sand; in mud, sediment grains
      are suspended in an organic matrix that fails by fracture. Macrofauna extend
      burrows through this elastic mud by fracture. Sand is granular and non-cohesive,
      enabling grains to more easily move relative to each other, and macrofaunal
      burrowers use fluidization or plastic rearrangement of grains. In both sand and
      mud, peristaltic movements apply normal forces and reduce shear. Excavation and
      localized grain compaction are mechanisms that plastically deform sediments and
      are effective in both mud and sand, with bulk excavation being used by larger
      organisms and localized compaction by smaller organisms. Mechanical boring of
      hard substrata is an extreme form of excavation in which no compaction of burrow
      walls occurs and grains are abraded with rigid, hard structures. Chemical boring
      involves secretion to dissolve or soften generally carbonate substrata. Despite
      substantial differences in the mechanics of the media, similar burrowing
      behaviors are effective in mud and sand. 

PMID- 25609782
TI  - Bird colour vision: behavioural thresholds reveal receptor noise.
AB  - Birds have impressive physiological adaptations for colour vision, including
      tetrachromacy and coloured oil droplets, yet it is not clear exactly how well
      birds can discriminate the reflecting object colours that they encounter in
      nature. With behavioural experiments, we determined colour discrimination
      thresholds of chickens in bright and dim light. We performed the experiments with
      two colour series, orange and green, covering two parts of chicken colour space.
      These experiments allowed us to compare behavioural results with model
      expectations and determine how different noise types limit colour discrimination.
      At intensities ranging from bright light to those corresponding to early dusk
      (250-10 cd m(-2)), we describe thresholds accurately by assuming a constant
      signal-to-noise ratio, in agreement with an invariant Weber fraction of Weber's
      law. Below this intensity, signal-to-noise ratio decreases and Weber's law is
      violated because photon-shot noise limits colour discrimination. In very dim
      light (below 0.05 cd m(-2) for the orange series or 0.2 cd m(-2) for the green
      series) colour discrimination is possibly constrained by dark noise, and the
      lowest intensity at which chickens can discriminate colours is 0.025 and 0.08 cd
      m(-2) for the orange and green series, respectively. Our results suggest that
      chickens use spatial pooling of cone outputs to mitigate photon-shot noise.
      Surprisingly, we found no difference between colour discrimination of chickens
      and humans tested with the same test in bright light.

PMID- 25609783
TI  - When hawks attack: animal-borne video studies of goshawk pursuit and prey-evasion
      strategies.
AB  - Video filmed by a camera mounted on the head of a Northern Goshawk (Accipiter
      gentilis) was used to study how the raptor used visual guidance to pursue prey
      and land on perches. A combination of novel image analysis methods and numerical
      simulations of mathematical pursuit models was used to determine the goshawk's
      pursuit strategy. The goshawk flew to intercept targets by fixing the prey at a
      constant visual angle, using classical pursuit for stationary prey, lures or
      perches, and usually using constant absolute target direction (CATD) for moving
      prey. Visual fixation was better maintained along the horizontal than vertical
      direction. In some cases, we observed oscillations in the visual fix on the prey,
      suggesting that the goshawk used finite-feedback steering. Video filmed from the
      ground gave similar results. In most cases, it showed goshawks intercepting prey
      using a trajectory consistent with CATD, then turning rapidly to attack by
      classical pursuit; in a few cases, it showed them using curving non-CATD
      trajectories. Analysis of the prey's evasive tactics indicated that only sharp
      sideways turns caused the goshawk to lose visual fixation on the prey, supporting
      a sensory basis for the surprising frequency and effectiveness of this tactic
      found by previous studies. The dynamics of the prey's looming image also
      suggested that the goshawk used a tau-based interception strategy. We interpret
      these results in the context of a concise review of pursuit-evasion in biology,
      and conjecture that some prey deimatic 'startle' displays may exploit tau-based
      interception. 

PMID- 25609784
TI  - Physiological and molecular responses of the spiny dogfish shark (Squalus
      acanthias) to high environmental ammonia: scavenging for nitrogen.
AB  - In teleosts, a branchial metabolon links ammonia excretion to Na(+) uptake via Rh
      glycoproteins and other transporters. Ureotelic elasmobranchs are thought to have
      low branchial ammonia permeability, and little is known about Rh function in this
      ancient group. We cloned Rh cDNAs (Rhag, Rhbg and Rhp2) and evaluated gill
      ammonia handling in Squalus acanthias. Control ammonia excretion was <5% of urea
      N excretion. Sharks exposed to high environmental ammonia (HEA; 1 mmol(-1)
      NH4HCO3) for 48 h exhibited active ammonia uptake against partial pressure and
      electrochemical gradients for 36 h before net excretion was re-established.
      Plasma total ammonia rose to seawater levels by 2 h, but dropped significantly
      below them by 24-48 h. Control DeltaP(NH3) (the partial pressure gradient of NH3)
      across the gills became even more negative (outwardly directed) during HEA.
      Transepithelial potential increased by 30 mV, negating a parallel rise in the
      Nernst potential, such that the outwardly directed NH4(+) electrochemical
      gradient remained unchanged. Urea-N excretion was enhanced by 90% from 12 to 48
      h, more than compensating for ammonia-N uptake. Expression of Rhp2 (gills,
      kidney) and Rhbg (kidney) did not change, but branchial Rhbg and erythrocytic
      Rhag declined during HEA. mRNA expression of branchial Na(+)/K(+)-ATPase (NKA)
      increased at 24 h and that of H(+)-ATPase decreased at 48 h, while expression of
      the potential metabolon components Na(+)/H(+) exchanger2 (NHE2) and carbonic
      anhydrase IV (CA-IV) remained unchanged. We propose that the gill of this
      nitrogen-limited predator is poised not only to minimize nitrogen loss by low
      efflux permeability to urea and ammonia but also to scavenge ammonia-N from the
      environment during HEA to enhance urea-N synthesis.

PMID- 25609785
TI  - Chromogenic behaviors of the Humboldt squid (Dosidicus gigas) studied in situ
      with an animal-borne video package.
AB  - Dosidicus gigas (Humboldt or jumbo flying squid) is an economically and
      ecologically influential species, yet little is known about its natural behaviors
      because of difficulties in studying this active predator in its oceanic
      environment. By using an animal-borne video package, National Geographic's
      Crittercam, we were able to observe natural behaviors in free-swimming D. gigas
      in the Gulf of California with a focus on color-generating (chromogenic)
      behaviors. We documented two dynamic displays without artificial lighting at
      depths of up to 70 m. One dynamic pattern, termed 'flashing' is characterized by
      a global oscillation (2-4 Hz) of body color between white and red. Flashing was
      almost always observed when other squid were visible in the video frame, and this
      behavior presumably represents intraspecific signaling. Amplitude and frequency
      of flashing can be modulated, and the phase relationship with another squid can
      also be rapidly altered. Another dynamic display termed 'flickering' was observed
      whenever flashing was not occurring. This behavior is characterized by irregular
      wave-like activity in neighboring patches of chromatophores, and the resulting
      patterns mimic reflections of down-welled light in the water column, suggesting
      that this behavior may provide a dynamic type of camouflage. Rapid and global
      pauses in flickering, often before a flashing episode, indicate that flickering
      is under inhibitory neural control. Although flashing and flickering have not
      been described in other squid, functional similarities are evident with other
      species. 

PMID- 25609786
TI  - Intersegmental coupling and recovery from perturbations in freely running
      cockroaches.
AB  - Cockroaches are remarkably stable runners, exhibiting rapid recovery from
      external perturbations. To uncover the mechanisms behind this important
      behavioral trait, we recorded leg kinematics of freely running animals in both
      undisturbed and perturbed trials. Functional coupling underlying inter-leg
      coordination was monitored before and during localized perturbations, which were
      applied to single legs via magnetic impulses. The resulting transient effects on
      all legs and the recovery times to normal pre-perturbation kinematics were
      studied. We estimated coupling architecture and strength by fitting experimental
      data to a six-leg-unit phase oscillator model. Using maximum-likelihood
      techniques, we found that a network with nearest-neighbor inter-leg coupling best
      fitted the data and that, although coupling strengths vary among preparations,
      the overall inputs entering each leg are approximately balanced and consistent.
      Simulations of models with different coupling strengths encountering
      perturbations suggest that the coupling schemes estimated from our experiments
      allow animals relatively fast and uniform recoveries from perturbations. 

PMID- 25609787
TI  - Remarks on the article on life-history traits in Drosophila populations selected
      for rapid development by Yadav and Sharma.

PMID- 25609788
TI  - Response to 'Remarks on the article on life-history traits in Drosophila
      populations selected for rapid development by Yadav and Sharma'.

PMID- 25609790
TI  - Ultrafast SNP analysis using the Burrows-Wheeler transform of short-read data.
AB  - MOTIVATION: Sequence-variation analysis is conventionally performed on mapping
      results that are highly redundant and occasionally contain undesirable heuristic
      biases. A straightforward approach to single-nucleotide polymorphism (SNP)
      analysis, using the Burrows-Wheeler transform (BWT) of short-read data, is
      proposed. RESULTS: The BWT makes it possible to simultaneously process
      collections of read fragments of the same sequences; accordingly, SNPs were found
      from the BWT much faster than from the mapping results. It took only a few
      minutes to find SNPs from the BWT (with a supplementary data, fragment depth of
      coverage [FDC]) using a desktop workstation in the case of human exome or
      transcriptome sequencing data and 20 min using a dual-CPU server in the case of
      human genome sequencing data. The SNPs found with the proposed method almost
      agreed with those found by a time-consuming state-of-the-art tool, except for the
      cases in which the use of fragments of reads led to sensitivity loss or
      sequencing depth was not sufficient. These exceptions were predictable in advance
      on the basis of minimum length for uniqueness (MLU) and FDC defined on the
      reference genome. Moreover, BWT and FDC were computed in less time than it took
      to get the mapping results, provided that the data were large enough.

PMID- 25609789
TI  - Wnt activity and basal niche position sensitize intestinal stem and progenitor
      cells to DNA damage.
AB  - Aging and carcinogenesis coincide with the accumulation of DNA damage and
      mutations in stem and progenitor cells. Molecular mechanisms that influence
      responses of stem and progenitor cells to DNA damage remain to be delineated.
      Here, we show that niche positioning and Wnt signaling activity modulate the
      sensitivity of intestinal stem and progenitor cells (ISPCs) to DNA damage. ISPCs
      at the crypt bottom with high Wnt/beta-catenin activity are more sensitive to DNA
      damage compared to ISPCs in position 4 with low Wnt activity. These differences
      are not induced by differences in cell cycle activity but relate to DNA damage
      dependent activation of Wnt signaling, which in turn amplifies DNA damage
      checkpoint activation. The study shows that instructed enhancement of Wnt
      signaling increases radio-sensitivity of ISPCs, while inhibition of Wnt signaling
      decreases it. These results provide a proof of concept that cell intrinsic levels
      of Wnt signaling modulate the sensitivity of ISPCs to DNA damage and
      heterogeneity in Wnt activation in the stem cell niche contributes to the
      selection of ISPCs in the context of DNA damage. 

PMID- 25609791
TI  - Bias in microRNA functional enrichment analysis.
AB  - MOTIVATION: Many studies have investigated the differential expression of
      microRNAs (miRNAs) in disease states and between different treatments, tissues
      and developmental stages. Given a list of perturbed miRNAs, it is common to
      predict the shared pathways on which they act. The standard test for functional
      enrichment typically yields dozens of significantly enriched functional
      categories, many of which appear frequently in the analysis of apparently
      unrelated diseases and conditions. RESULTS: We show that the most commonly used
      functional enrichment test is inappropriate for the analysis of sets of genes
      targeted by miRNAs. The hypergeometric distribution used by the standard method
      consistently results in significant P-values for functional enrichment for
      targets of randomly selected miRNAs, reflecting an underlying bias in the
      predicted gene targets of miRNAs as a whole. We developed an algorithm to measure
      enrichment using an empirical sampling approach, and applied this in a reanalysis
      of the gene ontology classes of targets of miRNA lists from 44 published studies.
      The vast majority of the miRNA target sets were not significantly enriched in any
      functional category after correction for bias. We therefore argue against
      continued use of the standard functional enrichment method for miRNA targets.

PMID- 25609792
TI  - GrammR: graphical representation and modeling of count data with application in
      metagenomics.
AB  - MOTIVATION: Microbiota compositions have great implications in human health, such
      as obesity and other conditions. As such, it is of great importance to cluster
      samples or taxa to visualize and discover community substructures. Graphical
      representation of metagenomic count data relies on two aspects, measure of
      dissimilarity between samples/taxa and algorithm used to estimate coordinates to
      study microbiota communities. UniFrac is a dissimilarity measure commonly used in
      metagenomic research, but it requires a phylogenetic tree. Principal coordinate
      analysis (PCoA) is a popular algorithm for estimating two-dimensional (2D)
      coordinates for graphical representation, although alternative and higher
      dimensional representations may reveal underlying community substructures
      invisible in 2D representations. RESULTS: We adapt a new measure of
      dissimilarity, penalized Kendall's tau-distance, which does not depend on a
      phylogenetic tree, and hence more readily applicable to a wider class of
      problems. Further, we propose to use metric multidimensional scaling (MDS) as an
      alternative to PCoA for graphical representation. We then devise a novel
      procedure for determining the number of clusters in conjunction with PAM (mPAM).
      We show superior performances with higher-dimensional representations. We further
      demonstrate the utility of mPAM for accurate clustering analysis, especially with
      higher-dimensional MDS models. Applications to two human microbiota datasets
      illustrate greater insights into the subcommunity structure with a higher
      dimensional analysis.

PMID- 25609793
TI  - MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics
      assembly via succinct de Bruijn graph.
AB  - MEGAHIT is a NGS de novo assembler for assembling large and complex metagenomics
      data in a time- and cost-efficient manner. It finished assembling a soil
      metagenomics dataset with 252 Gbps in 44.1 and 99.6 h on a single computing node
      with and without a graphics processing unit, respectively. MEGAHIT assembles the
      data as a whole, i.e. no pre-processing like partitioning and normalization was
      needed. When compared with previous methods on assembling the soil data, MEGAHIT
      generated a three-time larger assembly, with longer contig N50 and average contig
      length; furthermore, 55.8% of the reads were aligned to the assembly, giving a
      fourfold improvement.

PMID- 25609794
TI  - MethylMix: an R package for identifying DNA methylation-driven genes.
AB  - DNA methylation is an important mechanism regulating gene transcription, and its
      role in carcinogenesis has been extensively studied. Hyper and hypomethylation of
      genes is an alternative mechanism to deregulate gene expression in a wide range
      of diseases. At the same time, high-throughput DNA methylation assays have been
      developed generating vast amounts of genome wide DNA methylation measurements.
      Yet, few tools exist that can formally identify hypo and hypermethylated genes
      that are predictive of transcription and thus functionally relevant for a
      particular disease. To accommodate this lack of tools, we developed MethylMix, an
      algorithm implemented in R to identify disease specific hyper and hypomethylated
      genes. MethylMix is based on a beta mixture model to identify methylation states
      and compares them with the normal DNA methylation state. MethylMix introduces a
      novel metric, the 'Differential Methylation value' or DM-value defined as the
      difference of a methylation state with the normal methylation state. Finally,
      matched gene expression data are used to identify, besides differential,
      transcriptionally predictive methylation states by focusing on methylation
      changes that effect gene expression. AVAILABILITY AND IMPLEMENTATION: MethylMix
      was implemented as an R package and is available in bioconductor.

PMID- 25609795
TI  - Large-scale extraction of brain connectivity from the neuroscientific literature.
AB  - MOTIVATION: In neuroscience, as in many other scientific domains, the primary
      form of knowledge dissemination is through published articles. One challenge for
      modern neuroinformatics is finding methods to make the knowledge from the
      tremendous backlog of publications accessible for search, analysis and the
      integration of such data into computational models. A key example of this is
      metascale brain connectivity, where results are not reported in a normalized
      repository. Instead, these experimental results are published in natural
      language, scattered among individual scientific publications. This lack of
      normalization and centralization hinders the large-scale integration of brain
      connectivity results. In this article, we present text-mining models to extract
      and aggregate brain connectivity results from 13.2 million PubMed abstracts and
      630 216 full-text publications related to neuroscience. The brain regions are
      identified with three different named entity recognizers (NERs) and then
      normalized against two atlases: the Allen Brain Atlas (ABA) and the atlas from
      the Brain Architecture Management System (BAMS). We then use three different
      extractors to assess inter-region connectivity. RESULTS: NERs and connectivity
      extractors are evaluated against a manually annotated corpus. The complete in
      litero extraction models are also evaluated against in vivo connectivity data
      from ABA with an estimated precision of 78%. The resulting database contains over
      4 million brain region mentions and over 100 000 (ABA) and 122 000 (BAMS)
      potential brain region connections. This database drastically accelerates
      connectivity literature review, by providing a centralized repository of
      connectivity data to neuroscientists.

PMID- 25609796
TI  - dslice: an R package for nonparametric testing of associations with application
      in QTL and gene set analysis.
AB  - Many statistical problems in bioinformatics and genetics can be formulated as the
      testing of associations between a categorical variable and a continuous variable.
      A dynamic slicing method was proposed for non-parametric dependence testing,
      which has been demonstrated to have higher powers compared with traditional
      methods such as Kolmogorov-Smirnov test. We introduce an R package dslice to
      facilitate the use of dynamic slicing method in bioinformatic applications such
      as quantitative trait loci study and gene set enrichment analysis. AVAILABILITY
      AND IMPLEMENTATION: dslice is implemented in Rcpp and available in the
      Comprehensive R Archive Network. The package is distributed under the GNU General
      Public License (version 2 or later).

PMID- 25609797
TI  - Topology-function conservation in protein-protein interaction networks.
AB  - MOTIVATION: Proteins underlay the functioning of a cell and the wiring of
      proteins in protein-protein interaction network (PIN) relates to their biological
      functions. Proteins with similar wiring in the PIN (topology around them) have
      been shown to have similar functions. This property has been successfully
      exploited for predicting protein functions. Topological similarity is also used
      to guide network alignment algorithms that find similarly wired proteins between
      PINs of different species; these similarities are used to transfer annotation
      across PINs, e.g. from model organisms to human. To refine these functional
      predictions and annotation transfers, we need to gain insight into the
      variability of the topology-function relationships. For example, a function may
      be significantly associated with specific topologies, while another function may
      be weakly associated with several different topologies. Also, the topology
      function relationships may differ between different species. RESULTS: To improve
      our understanding of topology-function relationships and of their conservation
      among species, we develop a statistical framework that is built upon canonical
      correlation analysis. Using the graphlet degrees to represent the wiring around
      proteins in PINs and gene ontology (GO) annotations to describe their functions,
      our framework: (i) characterizes statistically significant topology-function
      relationships in a given species, and (ii) uncovers the functions that have
      conserved topology in PINs of different species, which we term topologically
      orthologous functions. We apply our framework to PINs of yeast and human,
      identifying seven biological process and two cellular component GO terms to be
      topologically orthologous for the two organisms.

PMID- 25609798
TI  - KMC 2: fast and resource-frugal k-mer counting.
AB  - MOTIVATION: Building the histogram of occurrences of every k-symbol long
      substring of nucleotide data is a standard step in many bioinformatics
      applications, known under the name of k-mer counting. Its applications include
      developing de Bruijn graph genome assemblers, fast multiple sequence alignment
      and repeat detection. The tremendous amounts of NGS data require fast algorithms
      for k-mer counting, preferably using moderate amounts of memory. RESULTS: We
      present a novel method for k-mer counting, on large datasets about twice faster
      than the strongest competitors (Jellyfish 2, KMC 1), using about 12 GB (or less)
      of RAM. Our disk-based method bears some resemblance to MSPKmerCounter, yet
      replacing the original minimizers with signatures (a carefully selected subset of
      all minimizers) and using (k, x)-mers allows to significantly reduce the I/O and
      a highly parallel overall architecture allows to achieve unprecedented processing
      speeds. For example, KMC 2 counts the 28-mers of a human reads collection with 44
      fold coverage (106 GB of compressed size) in about 20 min, on a 6-core Intel i7
      PC with an solid-state disk.

PMID- 25609799
TI  - The lysine residues within the human ribosomal protein S17 sequence naturally
      inserted into the viral nonstructural protein of a unique strain of hepatitis E
      virus are important for enhanced virus replication.
AB  - Hepatitis E virus (HEV) is an important but extremely understudied human
      pathogen. Due largely to the lack of an efficient cell culture system for HEV,
      the molecular mechanisms of HEV replication and pathogenesis are poorly
      understood. Recently, a unique genotype 3 strain of HEV recovered from a
      chronically infected patient was adapted for growth in HepG2C3A human hepatoma
      cells. The adaptation of the Kernow C-1 P6 HEV to propagate in HepG2C3A cells
      selected for a rare virus recombinant that contains an insertion of a 171
      nucleotide sequence encoding amino acids 21 to 76 of the human ribosomal protein
      S17 (RPS17) within the hypervariable region (HVR) of the HEV ORF1 protein. When
      the RPS17 insertion was placed into a strain of genotype 1 HEV which infects only
      humans, it expanded the host range of the virus, allowing it to infect cell lines
      from multiple animal species, including cow, dog, cat, chicken, and hamster. In
      this study, we utilized forward and reverse genetics to attempt to define which
      aspects of the RPS17 insertion allow for the ability of the Kernow C-1 P6 HEV to
      adapt in cell culture and allow for expanded host tropism. We demonstrate that
      the RPS17 sequence insertion in HEV bestows novel nuclear/nucleolar trafficking
      capabilities to the ORF1 protein of Kernow P6 HEV and that lysine residues within
      the RPS17 insertion, but not nuclear localization of the ORF1 protein, correlate
      with the enhanced replication of the HEV Kernow C-1 P6 strain. The results from
      this study have important implications for understanding the mechanism of cross
      species infection and replication of HEV. IMPORTANCE: HEV is an important
      pathogen worldwide. The virus causes high mortality (up to 30%) in pregnant women
      and has been recognized to cause chronic hepatitis in immunocompromised
      populations. The life cycle of HEV has been understudied due to a lack of
      sufficient cell culture systems in which to propagate the virus. Recently,
      insertions and rearrangements of the hypervariable region (HVR) within the HEV
      genome, allowing for cell culture adaptation and expansion of the host range,
      have been reported. We utilized these cell culture-adapted HEV strains to assess
      how the HVR may be involved in virus replication and host range. We provide
      evidence that insertion of the RPS17 sequence in HEV likely confers nuclear
      trafficking capabilities to the nonstructural protein of the virus and that
      lysine residues within the RPS17 insertion are important for enhanced replication
      of the virus. These data will help to elucidate the mechanism of cross-species
      infection of HEV in the future.

PMID- 25609800
TI  - Phenotypic and functional characterization of herpes simplex virus glycoprotein B
      epitope-specific effector and memory CD8+ T cells from symptomatic and
      asymptomatic individuals with ocular herpes.
AB  - Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8(+) T cells
      protect mice from herpes infection and disease. However, whether and which HSV-1
      gB-specific CD8(+) T cells play a key role in the "natural" protection seen in
      HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had
      clinical herpes disease) remain to be determined. In this study, we have
      dissected the phenotypes and the functions of HSV-1 gB-specific CD8(+) T cells
      from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP)
      individuals (with a history of numerous episodes of recurrent ocular herpes
      disease). We found the following. (i) Healthy ASYMP individuals maintained a
      significantly higher proportion of differentiated HSV-1 gB-specific effector
      memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)).
      In contrast, SYMP patients had frequent less-differentiated central memory CD8(+)
      T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)). (ii) ASYMP
      individuals had significantly higher proportions of multifunctional effector
      CD8(+) T cells which responded mainly to gB342-350 and gB561-569 "ASYMP"
      epitopes, and simultaneously produced IFN-gamma, CD107(a/b), granzyme B, and
      perforin. In contrast, effector CD8(+) T cells from SYMP individuals were mostly
      monofunctional and were directed mainly against nonoverlapping gB17-25 and gB183
      191 "SYMP" epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model
      of ocular herpes with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP"
      CD8(+) TCM cell epitopes, induced a strong CD8(+) T cell-dependent protective
      immunity against ocular herpes infection and disease. Our findings provide
      insights into the role of HSV-specific CD8(+) TEM cells in protection against
      herpes and should be considered in the development of an effective vaccine.
      IMPORTANCE: A significantly higher proportion of differentiated and
      multifunctional HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells)
      (CD45RA(low) CCR7(low) CD44(high) CD62L(low)) were found in healthy ASYMP
      individuals who are seropositive for HSV-1 but never had any recurrent herpetic
      disease, while there were frequent less-differentiated and monofunctional central
      memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high))
      in SYMP patients. Immunization with "ASYMP" CD8(+) TEM cell epitopes, but not
      with "SYMP" CD8(+) TCM cell epitopes, induced a strong protective HSV-specific
      CD8(+) T cell response in HLA-A*02:01 transgenic mice. These findings are
      important for the development of a safe and effective T cell-based herpes
      vaccine.

PMID- 25609801
TI  - Characterization of hepatitis C virus interaction with heparan sulfate
      proteoglycans.
AB  - Hepatitis C virus (HCV) entry involves binding to cell surface heparan sulfate
      (HS) structures. However, due to the lipoprotein-like structure of HCV, the exact
      contribution of virion components to this interaction remains controversial.
      Here, we investigated the relative contribution of HCV envelope proteins and
      apolipoprotein E in the HS-binding step. Deletion of hypervariable region 1, a
      region previously proposed to be involved in HS binding, did not alter HCV virion
      binding to HS, indicating that this region is not involved in this interaction in
      the context of a viral infection. Patient sera and monoclonal antibodies
      recognizing different regions of HCV envelope glycoproteins were also used in a
      pulldown assay with beads coated with heparin, a close HS structural homologue.
      Although isolated HCV envelope glycoproteins could interact with heparin, none of
      these antibodies was able to interfere with the virion-heparin interaction,
      strongly suggesting that at the virion surface, HCV envelope glycoproteins are
      not accessible for HS binding. In contrast, results from kinetic studies, heparin
      pulldown experiments, and inhibition experiments with anti-apolipoprotein E
      antibodies indicated that this apolipoprotein plays a major role in HCV-HS
      interaction. Finally, characterization of the HS structural determinants required
      for HCV infection by silencing of the enzymes involved in the HS biosynthesis
      pathway and by competition with modified heparin indicated that N- and 6-O
      sulfation but not 2-O-sulfation is required for HCV infection and that the
      minimum HS oligosaccharide length required for HCV infection is a decasaccharide.
      Together, these data indicate that HCV hijacks apolipoprotein E to initiate its
      interaction with specific HS structures. IMPORTANCE: Hepatitis C is a global
      health problem. Hepatitis C virus (HCV) infects approximately 130 million
      individuals worldwide, with the majority of cases remaining undiagnosed and
      untreated. In most infected individuals, the virus evades the immune system and
      establishes a chronic infection. As a consequence, hepatitis C is the leading
      cause of cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver
      transplantation. Virus infection is initiated by entry of the virus into the host
      cell. In this study, we provide new insights into the viral and cellular
      determinants involved in the first step of HCV entry, the binding of the virus to
      host cells. We show that apolipoprotein E is likely responsible for virus binding
      to heparan sulfate and that N- and 6-O-sulfation of the heparan sulfate
      proteoglycans is required for HCV infection. In addition, the minimal HS length
      unit required for HCV infection is a decasaccharide.

PMID- 25609802
TI  - A novel humanized antibody neutralizes H5N1 influenza virus via two different
      mechanisms.
AB  - Highly pathogenic avian influenza virus subtype H5N1 continues to be a severe
      threat to public health, as well as the poultry industry, because of its high
      lethality and antigenic drift rate. Neutralizing monoclonal antibodies (MAbs) can
      serve as a useful tool for preventing, treating, and detecting H5N1. In the
      present study, humanized H5 antibody 8A8 was developed from a murine H5 MAb. Both
      the humanized and mouse MAbs presented positive activity in hemagglutination
      inhibition (HI), virus neutralization, and immunofluorescence assays against a
      wide range of H5N1 strains. Interestingly, both human and murine 8A8 antibodies
      were able to detect H5 in Western blot assays under reducing conditions. Further,
      by sequencing of escape mutants, the conformational epitope of 8A8 was found to
      be located within the receptor binding domain (RBD) of H5. The linear epitope of
      8A8 was identified by Western blotting of overlapping fragments and substitution
      mutant forms of HA1. Reverse genetic H5N1 strains with individual mutations in
      either the conformational or the linear epitope were generated and characterized
      in a series of assays, including HI, postattachment, and cell-cell fusion
      inhibition assays. The results indicate that for 8A8, virus neutralization
      mediated by RBD blocking relies on the conformational epitope while binding to
      the linear epitope contributes to the neutralization by inhibiting membrane
      fusion. Taken together, the results of this study show that a novel humanized H5
      MAb binds to two types of epitopes on HA, leading to virus neutralization via two
      mechanisms. IMPORTANCE: Recurrence of the highly pathogenic avian influenza virus
      subtype H5N1 in humans and poultry continues to be a serious public health
      concern. Preventive and therapeutic measures against influenza A viruses have
      received much interest in the context of global efforts to combat the current and
      future pandemics. Passive immune therapy is considered to be the most effective
      and economically prudent preventive strategy against influenza virus besides
      vaccination. It is important to develop a humanized neutralizing monoclonal
      antibody (MAb) against all of the clades of H5N1. For the first time, we report
      in this study that a novel humanized H5 MAb binds to two types of epitopes on HA,
      leading to virus neutralization via two mechanisms. These findings further deepen
      our understanding of influenza virus neutralization.

PMID- 25609803
TI  - Influenza viruses with receptor-binding N1 neuraminidases occur sporadically in
      several lineages and show no attenuation in cell culture or mice.
AB  - In nearly all characterized influenza viruses, hemagglutinin (HA) is the receptor
      binding protein while neuraminidase (NA) is a receptor-cleaving protein that aids
      in viral release. However, in recent years, several groups have described point
      mutations that confer receptor-binding activity on NA, albeit in laboratory
      rather than natural settings. One of these mutations, D151G, appears to arise in
      the NA of recent human H3N2 viruses upon passage in tissue culture. We
      inadvertently isolated the second of these mutations, G147R, in the NA of the lab
      adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered virus
      in the lab. G147R also occurs at low frequencies in the reported sequences of
      viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), human
      seasonal H1N1, and chicken H5N1. Here we reconstructed a representative G147R NA
      from each of these lineages and found that all of the proteins have acquired the
      ability to bind an unknown cellular receptor while retaining substantial
      sialidase activity. We then reconstructed a virus with the HA and NA of a
      reported G147R pdmH1N1 variant and found no attenuation of viral replication in
      cell culture or change in pathogenesis in mice. Furthermore, the G147R virus had
      modestly enhanced resistance to neutralization by the Fab of an antibody against
      the receptor-binding pocket of HA, although it remained completely sensitive to
      the full-length IgG. Overall, our results suggest that circulating N1 viruses
      occasionally may acquire the G147R NA receptor-binding mutation without
      impairment of replicative capacity. IMPORTANCE: Influenza viruses have two main
      proteins on their surface: one (hemagglutinin) binds incoming viruses to cells,
      while the other (neuraminidase) helps release newly formed viruses from these
      same cells. Here we characterize unusual mutant neuraminidases that have acquired
      the ability to bind to cells. We show that the mutation that allows neuraminidase
      to bind cells has no apparent adverse effect on viral replication but does make
      the virus modestly more resistant to a fragment of an antibody that blocks the
      normal hemagglutinin-mediated mode of viral attachment. Our results suggest that
      viruses with receptor-binding neuraminidases may occur at low levels in
      circulating influenza virus lineages.

PMID- 25609804
TI  - The susceptibility of primate lentiviruses to nucleosides and Vpx during
      infection of dendritic cells is regulated by CA.
AB  - The block toward human immunodeficiency virus type 1 (HIV-1) infection of
      dendritic cells (DCs) can be relieved by Vpx (viral protein X), which degrades
      sterile alpha motif-hydroxylase domain 1 (SAMHD1) or by exogenously added
      deoxynucleosides (dNs), lending support to the hypothesis that SAMHD1 acts by
      limiting deoxynucleoside triphosphates (dNTPs). This notion has, however, been
      questioned. We show that while dNs and Vpx increase the infectivity of HIV-1,
      only the latter restores the infectivity of a simian immunodeficiency virus of
      macaques variant, SIVMACDeltaVpx virus. This distinct behavior seems to map to
      CA, suggesting that species-specific CA interactors modulate infection of DCs. 

PMID- 25609805
TI  - Antibody titer has positive predictive value for vaccine protection against
      challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian
      influenza viruses from Indonesia.
AB  - Vaccines are used in integrated control strategies to protect poultry against
      H5N1 high-pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in
      Indonesia in 2003, and vaccination was initiated in 2004, but reports of vaccine
      failures began to emerge in mid-2005. This study investigated the role of
      Indonesian licensed vaccines, specific vaccine seed strains, and emerging variant
      field viruses as causes of vaccine failures. Eleven of 14 licensed vaccines
      contained the manufacturer's listed vaccine seed strains, but 3 vaccines
      contained a seed strain different from that listed on the label. Vaccines
      containing A/turkey/Wisconsin/1968 (WI/68), A/chicken/Mexico/28159-232/1994
      (Mex/94), and A/turkey/England/N28/1973 seed strains had high serological potency
      in chickens (geometric mean hemagglutination inhibition [HI] titers, >= 1:169),
      but vaccines containing strain A/chicken/Guangdong/1/1996 generated by reverse
      genetics (rg; rgGD/96), A/chicken/Legok/2003 (Legok/03),
      A/chicken/Vietnam/C57/2004 generated by rg (rgVN/04), or A/chicken/Legok/2003
      generated by rg (rgLegok/03) had lower serological potency (geometric mean HI
      titers, <= 1:95). In challenge studies, chickens immunized with any of the H5
      avian influenza vaccines were protected against A/chicken/West Java/SMI-HAMD/2006
      (SMI-HAMD/06) and were partially protected against A/chicken/Papua/TA5/2006
      (Papua/06) but were not protected against A/chicken/West Java/PWT-WIJ/2006
      (PWT/06). Experimental inactivated vaccines made with PWT/06 HPAI virus or rg
      generated PWT/06 low-pathogenicity avian influenza (LPAI) virus seed strains
      protected chickens from lethal challenge, as did a combination of a commercially
      available live fowl poxvirus vaccine expressing the H5 influenza virus gene and
      inactivated Legok/03 vaccine. These studies indicate that antigenic variants did
      emerge in Indonesia following widespread H5 avian influenza vaccine usage, and
      efficacious inactivated vaccines can be developed using antigenic variant wild
      type viruses or rg-generated LPAI virus seed strains containing the hemagglutinin
      and neuraminidase genes of wild-type viruses. IMPORTANCE: H5N1 high-pathogenicity
      avian influenza (HPAI) virus has become endemic in Indonesian poultry, and such
      poultry are the source of virus for birds and mammals, including humans.
      Vaccination has become a part of the poultry control strategy, but vaccine
      failures have occurred in the field. This study identified possible causes of
      vaccine failure, which included the use of an unlicensed virus seed strain and
      induction of low levels of protective antibody because of an insufficient
      quantity of vaccine antigen. However, the most important cause of vaccine failure
      was the appearance of drift variant field viruses that partially or completely
      overcame commercial vaccine-induced immunity. Furthermore, experimental vaccines
      using inactivated wild-type virus or reverse genetics-generated vaccines
      containing the hemagglutinin and neuraminidase genes of wild-type drift variant
      field viruses were protective. These studies indicate the need for surveillance
      to identify drift variant viruses in the field and update licensed vaccines when
      such variants appear.

PMID- 25609806
TI  - Requirement for chloride channel function during the hepatitis C virus life
      cycle.
AB  - Hepatocytes express an array of plasma membrane and intracellular ion channels,
      yet their role during the hepatitis C virus (HCV) life cycle remains largely
      undefined. Here, we show that HCV increases intracellular hepatic chloride (Cl(
      )) influx that can be inhibited by selective Cl(-) channel blockers. Through
      pharmacological and small interfering RNA (siRNA)-mediated silencing, we
      demonstrate that Cl(-) channel inhibition is detrimental to HCV replication. This
      represents the first observation of the involvement of Cl(-) channels during the
      HCV life cycle. 

PMID- 25609807
TI  - Interleukin-1- and type I interferon-dependent enhanced immunogenicity of an
      NYVAC-HIV-1 Env-Gag-Pol-Nef vaccine vector with dual deletions of type I and type
      II interferon-binding proteins.
AB  - NYVAC, a highly attenuated, replication-restricted poxvirus, is a safe and
      immunogenic vaccine vector. Deletion of immune evasion genes from the poxvirus
      genome is an attractive strategy for improving the immunogenic properties of
      poxviruses. Using systems biology approaches, we describe herein the enhanced
      immunological profile of NYVAC vectors expressing the HIV-1 clade C env, gag,
      pol, and nef genes (NYVAC-C) with single or double deletions of genes encoding
      type I (DeltaB19R) or type II (DeltaB8R) interferon (IFN)-binding proteins.
      Transcriptomic analyses of human monocytes infected with NYVAC-C, NYVAC-C with
      the B19R deletion (NYVAC-C-DeltaB19R), or NYVAC-C with B8R and B19R deletions
      (NYVAC-C-DeltaB8RB19R) revealed a concerted upregulation of innate immune
      pathways (IFN-stimulated genes [ISGs]) of increasing magnitude with NYVAC-C
      DeltaB19R and NYVAC-C-DeltaB8RB19R than with NYVAC-C. Deletion of B8R and B19R
      resulted in an enhanced activation of IRF3, IRF7, and STAT1 and the robust
      production of type I IFNs and of ISGs, whose expression was inhibited by anti
      type I IFN antibodies. Interestingly, NYVAC-C-DeltaB8RB19R induced the production
      of much higher levels of proinflammatory cytokines (tumor necrosis factor [TNF],
      interleukin-6 [IL-6], and IL-8) than NYVAC-C or NYVAC-C-DeltaB19R as well as a
      strong inflammasome response (caspase-1 and IL-1beta) in infected monocytes. Top
      network analyses showed that this broad response mediated by the deletion of B8R
      and B19R was organized around two upregulated gene expression nodes (TNF and
      IRF7). Consistent with these findings, monocytes infected with NYVAC-C
      DeltaB8RB19R induced a stronger type I IFN-dependent and IL-1-dependent
      allogeneic CD4(+) T cell response than monocytes infected with NYVAC-C or NYVAC-C
      DeltaB19R. Dual deletion of type I and type II IFN immune evasion genes in NYVAC
      markedly enhanced its immunogenic properties via its induction of the increased
      expression of type I IFNs and IL-1beta and make it an attractive candidate HIV
      vaccine vector. IMPORTANCE: NYVAC is a replication-deficient poxvirus developed
      as a vaccine vector against HIV. NYVAC expresses several genes known to impair
      the host immune defenses by interfering with innate immune receptors, cytokines,
      or interferons. Given the crucial role played by interferons against viruses, we
      postulated that targeting the type I and type II decoy receptors used by poxvirus
      to subvert the host innate immune response would be an attractive approach to
      improve the immunogenicity of NYVAC vectors. Using systems biology approaches, we
      report that deletion of type I and type II IFN immune evasion genes in NYVAC
      poxvirus resulted in the robust expression of type I IFNs and interferon
      stimulated genes (ISGs), a strong activation of the inflammasome, and upregulated
      expression of IL-1beta and proinflammatory cytokines. Dual deletion of type I and
      type II IFN immune evasion genes in NYVAC poxvirus improves its immunogenic
      profile and makes it an attractive candidate HIV vaccine vector.

PMID- 25609808
TI  - Structure of the extracellular domain of matrix protein 2 of influenza A virus in
      complex with a protective monoclonal antibody.
AB  - The extracellular domain of influenza A virus matrix protein 2 (M2e) is conserved
      and is being evaluated as a quasiuniversal influenza A vaccine candidate. We
      describe the crystal structure at 1.6 A resolution of M2e in complex with the Fab
      fragment of an M2e-specific monoclonal antibody that protects against influenza A
      virus challenge. This antibody binds M2 expressed on the surfaces of cells
      infected with influenza A virus. Five out of six complementary determining
      regions interact with M2e, and three highly conserved M2e residues are critical
      for this interaction. In this complex, M2e adopts a compact U-shaped conformation
      stabilized in the center by the highly conserved tryptophan residue in M2e. This
      is the first description of the three-dimensional structure of M2e. IMPORTANCE:
      M2e of influenza A is under investigation as a universal influenza A vaccine, but
      its three-dimensional structure is unknown. We describe the structure of M2e
      stabilized with an M2e-specific monoclonal antibody that recognizes natural M2.
      We found that the conserved tryptophan is positioned in the center of the U
      shaped structure of M2e and stabilizes its conformation. The structure also
      explains why previously reported in vivo escape viruses, selected with a similar
      monoclonal antibody, carried proline residue substitutions at position 10 in M2.

PMID- 25609809
TI  - High secretion of interferons by human plasmacytoid dendritic cells upon
      recognition of Middle East respiratory syndrome coronavirus.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as
      the causative agent of a severe respiratory disease with a fatality rate of
      approximately 30%. The high virulence and mortality rate prompted us to analyze
      aspects of MERS-CoV pathogenesis, especially its interaction with innate immune
      cells such as antigen-presenting cells (APCs). Particularly, we analyzed
      secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells,
      macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by
      plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation
      with MERS-CoV. Production of large amounts of type I and III IFNs was induced
      exclusively in human pDCs, which were significantly higher than IFN induction by
      severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the
      absence of productive replication. However, receptor binding, endosomal uptake,
      and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing
      of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and
      subsequent N protein expression were evident in infected pDCs, indicating
      abortive infection. Taken together, our results point toward dipeptidyl peptidase
      4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by
      MERS-CoV. However, the replication cycle is stopped after early gene expression.
      In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection.
      Knowledge of such IFN responses supports our understanding of MERS-CoV
      pathogenesis and is critical for the choice of treatment options. IMPORTANCE:
      MERS-CoV causes a severe respiratory disease with high fatality rates in human
      patients. Recently, confirmed human cases have increased dramatically in both
      number and geographic distribution. Understanding the pathogenesis of this highly
      pathogenic CoV is crucial for developing successful treatment strategies. This
      study elucidates the interaction of MERS-CoV with APCs and pDCs, particularly the
      induction of type I and III IFN secretion. Human pDCs are the immune cell
      population sensing MERS-CoV but secrete significantly larger amounts of IFNs,
      especially IFN-alpha, than in response to SARS-CoV. A model for molecular virus
      host interactions is presented outlining IFN induction in pDCs. The massive IFN
      secretion upon contact suggests a critical role of this mechanism for the high
      degree of immune activation observed during MERS-CoV infection.

PMID- 25609811
TI  - Local evolutionary patterns of human respiratory syncytial virus derived from
      whole-genome sequencing.
AB  - Human respiratory syncytial virus (RSV) is associated with severe childhood
      respiratory infections. A clear description of local RSV molecular epidemiology,
      evolution, and transmission requires detailed sequence data and can inform new
      strategies for virus control and vaccine development. We have generated 27
      complete or nearly complete genomes of RSV from hospitalized children attending a
      rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a
      novel full-genome deep-sequencing process. Phylogenetic analysis of the new
      genomes demonstrated the existence and cocirculation of multiple genotypes in
      both RSV A and B groups in Kilifi. Comparison of local versus global strains
      demonstrated that most RSV A variants observed locally in Kilifi were also seen
      in other parts of the world, while the Kilifi RSV B genomes encoded a high degree
      of variation that was not observed in other parts of the world. The nucleotide
      substitution rates for the individual open reading frames (ORFs) were highest in
      the regions encoding the attachment (G) glycoprotein and the NS2 protein. The
      analysis of RSV full genomes, compared to subgenomic regions, provided more
      precise estimates of the RSV sequence changes and revealed important patterns of
      RSV genomic variation and global movement. The novel sequencing method and the
      new RSV genomic sequences reported here expand our knowledge base for large-scale
      RSV epidemiological and transmission studies. IMPORTANCE: The new RSV genomic
      sequences and the novel sequencing method reported here provide important data
      for understanding RSV transmission and vaccine development. Given the complex
      interplay between RSV A and RSV B infections, the existence of local RSV B
      evolution is an important factor in vaccine deployment.

PMID- 25609810
TI  - Identification of amino acid substitutions supporting antigenic change of
      influenza A(H1N1)pdm09 viruses.
AB  - The majority of currently circulating influenza A(H1N1) viruses are antigenically
      similar to the virus that caused the 2009 influenza pandemic. However, antigenic
      variants are expected to emerge as population immunity increases. Amino acid
      substitutions in the hemagglutinin protein can result in escape from neutralizing
      antibodies, affect viral fitness, and change receptor preference. In this study,
      we constructed mutants with substitutions in the hemagglutinin of
      A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that
      may contribute to emergence of antigenic variants in the human population. Our
      analysis revealed that single substitutions affecting the loop that consists of
      amino acid positions 151 to 159 located adjacent to the receptor binding site
      caused escape from ferret and human antibodies elicited after primary
      A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in
      similar or increased replication efficiency in vitro compared to that of the
      virus carrying the wild-type hemagglutinin and did not result in a change of
      receptor preference. However, none of the substitutions was sufficient for escape
      from the antibodies in sera from individuals that experienced both seasonal and
      pandemic A(H1N1) virus infections. These results suggest that antibodies directed
      against epitopes on seasonal A(H1N1) viruses contribute to neutralization of
      A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible
      substitutions that could lead to escape from population immunity. IMPORTANCE:
      Influenza A viruses can cause significant morbidity and mortality in humans.
      Amino acid substitutions in the hemagglutinin protein can result in escape from
      antibody-mediated neutralization. This allows the virus to reinfect individuals
      that have acquired immunity to previously circulating strains through infection
      or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain
      antigenically similar to the virus that caused the 2009 influenza pandemic.
      However, antigenic variants are expected to emerge as a result of increasing
      population immunity. We show that single amino acid substitutions near the
      receptor binding site were sufficient to escape from antibodies specific for
      A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections
      with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified
      substitutions in A(H1N1)pdm09 viruses that support escape from population
      immunity but also suggested that the number of potential escape variants is
      limited by previous exposure to seasonal A(H1N1) viruses.

PMID- 25609812
TI  - Tom70 mediates Sendai virus-induced apoptosis on mitochondria.
AB  - Virus infection triggers immediate innate immune responses. Apoptosis represents
      another effective means to restrict virus invasion, besides robust expression of
      host cytokines and chemokines. IRF3 was recently demonstrated to be indispensable
      for Sendai virus (SeV)-induced apoptosis, but the underlying mechanism is not
      fully understood. Here we report that a dynamic protein complex,
      Tom70/Hsp90/IRF3/Bax, mediates SeV-induced apoptosis. The cytosolic proapoptotic
      protein Bax interacts specifically with IRF3 upon virus infection. The
      mitochondrial outer membrane protein Tom70 recruits IRF3 to mitochondria via
      Hsp90. Consequently, the relocation of Bax onto mitochondria induces the leakage
      of cytochrome c into the cytosol and initiates the corresponding apoptosis.
      Interestingly, IKK-i is essential for this apoptosis, whereas TBK1 is
      dispensable. Collectively, our study characterizes a novel protein complex that
      is important for SeV-induced apoptosis. IMPORTANCE: Apoptosis is an effective
      means of sacrificing virus-infected cells and restraining the spread of virus. In
      this study, we demonstrate that IRF3 associates with Bax upon virus infection.
      Tom70 recruits this protein complex to the mitochondrial outer membrane through
      Hsp90, which thus induces the release of cytochrome c into the cytosol,
      initiating virus-induced apoptosis. Interestingly, IKK-i plays an essential role
      in this activation. This study uncovers a novel mechanism of SeV-induced
      apoptosis.

PMID- 25609813
TI  - Identification of PB2 mutations responsible for the efficient replication of H5N1
      influenza viruses in human lung epithelial cells.
AB  - Highly pathogenic H5N1 avian influenza viruses have caused outbreaks among
      poultry worldwide, resulting in sporadic infections in humans with approximately
      60% mortality. However, efficient transmission of H5N1 viruses among humans has
      yet to occur, suggesting that further adaptation of H5N1 viruses to humans is
      required for their efficient transmission among humans. The viral determinants
      for efficient replication in humans are currently poorly understood. Here, we
      report that the polymerase PB2 protein of an H5N1 influenza virus isolated from a
      human in Vietnam (A/Vietnam/UT36285/2010, virus 36285) increased the growth
      ability of an avian H5N1 virus (A/wild bird/Anhui/82/2005, virus Wb/AH82) in
      human lung epithelial A549 cells (however, the reassortant virus did not
      replicate more efficiently than human 36285 virus). Furthermore, we demonstrate
      that the amino acid residues at positions 249, 309, and 339 of the PB2 protein
      from this human isolate were responsible for its efficient replication in A549
      cells. PB2 residues 249G and 339M, which are found in the human H5N1 virus, are
      rare in H5N1 viruses from both human and avian sources. Interestingly, PB2-249G
      is found in over 30% of human seasonal H3N2 viruses, which suggests that H5N1
      viruses may replicate well in human cells when they acquire this mutation. Our
      data are of value to H5N1 virus surveillance. IMPORTANCE: Highly pathogenic H5N1
      avian influenza viruses must acquire mutations to overcome the species barrier
      between avian species and humans. When H5N1 viruses replicate in human
      respiratory cells, they can acquire amino acid mutations that allow them to adapt
      to humans through continuous selective pressure. Several amino acid mutations
      have been shown to be advantageous for virus adaptation to mammalian hosts. Here,
      we found that amino acid changes at positions 249, 309, and 339 of PB2 contribute
      to efficient replication of avian H5N1 viruses in human lung cells. These
      findings are beneficial for evaluating the pandemic risk of circulating avian
      viruses and for further functional analysis of PB2.

PMID- 25609814
TI  - Control of hepatitis C virus replication in mouse liver-derived cells by MAVS
      dependent production of type I and type III interferons.
AB  - Hepatitis C virus (HCV) efficiently infects only humans and chimpanzees. Although
      the detailed mechanisms responsible for this narrow species tropism remain
      elusive, recent evidence has shown that murine innate immune responses
      efficiently suppress HCV replication. Therefore, poor adaptation of HCV to evade
      and/or counteract innate immune responses may prevent HCV replication in mice.
      The HCV NS3-4A protease cleaves human MAVS, a key cellular adaptor protein
      required for RIG-I-like receptor (RLR)-dependent innate immune signaling.
      However, it is unclear if HCV interferes with mouse MAVS function equally well.
      Moreover, MAVS-dependent signaling events that restrict HCV replication in mouse
      cells were incompletely defined. Thus, we quantified the ability of HCV NS3-4A to
      counteract mouse and human MAVS. HCV NS3-4A similarly diminished both human and
      mouse MAVS-dependent signaling in human and mouse cells. Moreover, replicon
      encoded protease cleaved a similar fraction of both MAVS variants. Finally, FLAG
      tagged MAVS proteins repressed HCV replication to similar degrees. Depending on
      MAVS expression, HCV replication in mouse liver cells triggered not only type I
      but also type III IFNs, which cooperatively repressed HCV replication. Mouse
      liver cells lacking both type I and III IFN receptors were refractory to MAVS
      dependent antiviral effects, indicating that the HCV-induced MAVS-dependent
      antiviral state depends on both type I and III IFN receptor signaling.
      IMPORTANCE: In this study, we found that HCV NS3-4A similarly diminished both
      human and mouse MAVS-dependent signaling in human and mouse cells. Therefore, it
      is unlikely that ineffective cleavage of mouse MAVS per se precludes HCV
      propagation in immunocompetent mouse liver cells. Hence, approaches to reinforce
      HCV replication in mouse liver cells (e.g., by expression of essential human
      replication cofactors) should not be thwarted by the poor ability of HCV to
      counteract MAVS-dependent antiviral signaling. In addition, we show that mouse
      MAVS induces both type I and type III IFNs, which together control HCV
      replication. Characterization of type I or type III-dependent interferon
      stimulated genes in these cells should help to identify key murine restriction
      factors that preclude HCV propagation in immunocompetent mouse liver cells.

PMID- 25609815
TI  - A trans-dominant form of Gag restricts Ty1 retrotransposition and mediates copy
      number control.
AB  - Saccharomyces cerevisiae and Saccharomyces paradoxus lack the conserved RNA
      interference pathway and utilize a novel form of copy number control (CNC) to
      inhibit Ty1 retrotransposition. Although noncoding transcripts have been
      implicated in CNC, here we present evidence that a truncated form of the Gag
      capsid protein (p22) or its processed form (p18) is necessary and sufficient for
      CNC and likely encoded by Ty1 internal transcripts. Coexpression of p22/p18 and
      Ty1 decreases mobility more than 30,000-fold. p22/p18 cofractionates with Ty1
      virus-like particles (VLPs) and affects VLP yield, protein composition, and
      morphology. Although p22/p18 and Gag colocalize in the cytoplasm, p22/p18
      disrupts sites used for VLP assembly. Glutathione S-transferase (GST) affinity
      pulldowns also suggest that p18 and Gag interact. Therefore, this intrinsic Gag
      like restriction factor confers CNC by interfering with VLP assembly and function
      and expands the strategies used to limit retroelement propagation. IMPORTANCE:
      Retrotransposons dominate the chromosomal landscape in many eukaryotes, can cause
      mutations by insertion or genome rearrangement, and are evolutionarily related to
      retroviruses such as HIV. Thus, understanding factors that limit transposition
      and retroviral replication is fundamentally important. The present work describes
      a retrotransposon-encoded restriction protein derived from the capsid gene of the
      yeast Ty1 element that disrupts virus-like particle assembly in a dose-dependent
      manner. This form of copy number control acts as a molecular rheostat, allowing
      high levels of retrotransposition when few Ty1 elements are present and
      inhibiting transposition as copy number increases. Thus, yeast and Ty1 have
      coevolved a form of copy number control that is beneficial to both "host and
      parasite." To our knowledge, this is the first Gag-like retrotransposon
      restriction factor described in the literature and expands the ways in which
      restriction proteins modulate retroelement replication.

PMID- 25609817
TI  - Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease
      etiology?
AB  - The genotype at polymorphic codon 129 of the PRNP gene has a profound influence
      on both phenotypic expression and prion strain susceptibility in humans. For
      example, while the most common sporadic Creutzfeldt-Jakob disease (CJD) subtype,
      sporadic CJD-MM1 (M1 strain), induces a single phenotype after experimental
      transmission regardless of the codon 129 genotype of the recipient animal, the
      phenotype elicited by sporadic CJD-VV2 (V2 strain), the second most common
      subtype, varies according to the host codon 129 genotype. In particular, the
      propagation of the V2 strain in codon 129 methionine homozygotes has been linked
      only to acquired forms of CJD such as plaque-type dura mater graft-associated CJD
      (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but
      has never been observed in sporadic CJD cases. In the present report, we describe
      atypical CJD cases carrying codon 129 methionine homozygosity, in a neurosurgeon
      and in a patient with a medical history of neurosurgery without dural grafting,
      showing the distinctive phenotypic features and transmission properties of plaque
      type dCJD. These findings raise the possibility that the two cases, previously
      thought to represent sporadic CJD, might actually represent acquired CJD caused
      by infection with the V2 strain. Thus, careful analyses of phenotypic features
      and transmission properties in atypical cases may be useful to distinguish
      acquired from sporadic cases of CJD. IMPORTANCE: Susceptibility to and phenotypic
      expression of Creutzfeldt-Jakob disease (CJD) depend on both the prion strain and
      genotype at polymorphic codon 129 of the PRNP gene. For example, propagation of
      the second most common sporadic CJD strain (V2 strain) into codon 129 methionine
      homozygotes has been linked to plaque-type dura mater graft-associated CJD
      (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but
      has never been observed in sporadic CJD. In the present report, we describe
      atypical CJD cases in a neurosurgeon and in a patient with a medical history of
      neurosurgery without dural grafting, showing the distinctive phenotypic features
      and transmission properties of plaque-type dCJD. These findings raise the
      possibility that the two cases, previously considered to represent sporadic CJD,
      might actually represent acquired CJD caused by infection with the V2 strain.

PMID- 25609816
TI  - Severe acute respiratory syndrome coronaviruses with mutations in the E protein
      are attenuated and promising vaccine candidates.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory
      disease with a mortality rate of 10%. A mouse-adapted SARS-CoV (SARS-CoV-MA15)
      lacking the envelope (E) protein (rSARS-CoV-MA15-DeltaE) is attenuated in vivo.
      To identify E protein regions and host responses that contribute to rSARS-CoV
      MA15-DeltaE attenuation, several mutants (rSARS-CoV-MA15-E*) containing point
      mutations or deletions in the amino-terminal or the carboxy-terminal regions of
      the E protein were generated. Amino acid substitutions in the amino terminus, or
      deletion of regions in the internal carboxy-terminal region of E protein, led to
      virus attenuation. Attenuated viruses induced minimal lung injury, diminished
      limited neutrophil influx, and increased CD4(+) and CD8(+) T cell counts in the
      lungs of BALB/c mice, compared to mice infected with the wild-type virus. To
      analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, differences
      in gene expression elicited by the native and mutant viruses in the lungs of
      infected mice were determined. Expression levels of a large number of
      proinflammatory cytokines associated with lung injury were reduced in the lungs
      of rSARS-CoV-MA15-E*-infected mice, whereas the levels of anti-inflammatory
      cytokines were increased, both at the mRNA and protein levels. These results
      suggested that the reduction in lung inflammation together with a more robust
      antiviral T cell response contributed to rSARS-CoV-MA15-E* attenuation. The
      attenuated viruses completely protected mice against challenge with the lethal
      parental virus, indicating that these viruses are promising vaccine candidates.
      IMPORTANCE: Human coronaviruses are important zoonotic pathogens. SARS-CoV caused
      a worldwide epidemic infecting more than 8,000 people with a mortality of around
      10%. Therefore, understanding the virulence mechanisms of this pathogen and
      developing efficacious vaccines are of high importance to prevent epidemics from
      this and other human coronaviruses. Previously, we demonstrated that a SARS-CoV
      lacking the E protein was attenuated in vivo. Here, we show that small deletions
      and modifications within the E protein led to virus attenuation, manifested by
      minimal lung injury, limited neutrophil influx to the lungs, reduced expression
      of proinflammatory cytokines, increased anti-inflammatory cytokine levels, and
      enhanced CD4(+) and CD8(+) T cell counts in vivo, suggesting that these phenomena
      contribute to virus attenuation. The attenuated mutants fully protected mice from
      challenge with virulent virus. These studies show that mutations in the E protein
      are not well tolerated and indicate that this protein is an excellent target for
      vaccine development.

PMID- 25609818
TI  - Narrowing of human influenza A virus-specific T cell receptor alpha and beta
      repertoires with increasing age.
AB  - Alterations in memory CD8 T cell responses may contribute to the high morbidity
      and mortality caused by seasonal influenza A virus (IAV) infections in older
      individuals. We questioned whether memory CD8 responses to this nonpersistent
      virus, to which recurrent exposure with new strains is common, changed over time
      with increasing age. Here, we show a direct correlation between increasing age
      and narrowing of the HLA-A2-restricted IAV Valpha and Vbeta T cell repertoires
      specific to M1 residues 58 to 66 (M158-66), which simultaneously lead to
      oligoclonal expansions, including the usage of a single identical VA12-JA29
      clonotype in all eight older donors. The Valpha repertoire of older individuals
      also had longer CDR3 regions with increased usage of G/A runs, whose molecular
      flexibility may enhance T cell receptor (TCR) promiscuity. Collectively, these
      results suggest that CD8 memory T cell responses to nonpersistent viruses like
      IAV in humans are dynamic, and with aging there is a reduced diversity but a
      preferential retention of T cell repertoires with features of enhanced cross
      reactivity. IMPORTANCE: With increasing age, the immune system undergoes drastic
      changes, and older individuals have declined resistance to infections.
      Vaccinations become less effective, and infection with influenza A virus in older
      individuals is associated with higher morbidity and mortality. Here, we
      questioned whether T cell responses directed against the highly conserved HLA-A2
      restricted M158-66 peptide of IAV evolves with increasing age. Specifically, we
      postulated that CD8 T cell repertoires narrow with recurrent exposure and may
      thus be less efficient in response to new infections with new strains of IAV.
      Detailed analyses of the VA and VB TCR repertoires simultaneously showed a direct
      correlation between increasing age and narrowing of the TCR repertoire. Features
      of the TCRs indicated potentially enhanced cross-reactivity in all older donors.
      In summary, T cell repertoire analysis in older individuals may be useful as one
      of the predictors of protection after vaccination.

PMID- 25609819
TI  - Evolution of the Bunyamwera virus polymerase to accommodate deletions within
      genomic untranslated region sequences.
AB  - The untranslated regions (UTR) present at the ends of bunyavirus genome segments
      are required for essential steps in the virus life cycle and provide signals for
      encapsidation by nucleocapsid protein and the promoters for RNA transcription and
      replication as well as for mRNA transcription termination. For the prototype
      bunyavirus, Bunyamwera virus (BUNV), only the terminal 11 nucleotides (nt) of the
      segments are identical. Thereafter, the UTRs are highly variable both in length
      and in sequence. Furthermore, apart from the conserved termini, the UTRs of
      different viruses are highly variable. We previously generated recombinant BUNV
      carrying the minimal UTRs on all three segments that were attenuated for growth
      in cell culture. Following serial passage of these viruses, the viruses acquired
      increased fitness, and amino acid changes were observed to accumulate in the
      viral polymerase (L protein) of most mutant viruses, with the vast majority of
      the amino acid changes occurring in the C-terminal region. The function of this
      domain within L remains unknown, but by using a minigenome assay we showed that
      it might be involved in UTR recognition. Moreover, we identified an amino acid
      mutation within the polymerase that, when introduced into an otherwise wild-type
      BUNV, resulted in a virus with a temperature-sensitive phenotype. Viruses
      carrying temperature-sensitive mutations are good candidates for the design of
      live attenuated vaccines. We suggest that a combination of stable deletions of
      the UTRs together with the introduction of temperature-sensitive mutations in
      both the nucleocapsid and the polymerase could be used to design live attenuated
      vaccines against serious pathogens within the family Bunyaviridae. IMPORTANCE:
      Virus growth in tissue culture can be attenuated by introduction of mutations in
      both coding and noncoding sequences. We generated attenuated Bunyamwera viruses
      by deleting sequences within both the 3' and 5' untranslated regions (UTR) on
      each genome segment and showed that the viruses regained fitness following serial
      passage in cell culture. The fitter viruses had acquired amino acid changes
      predominantly in the C-terminal domain of the viral polymerase (L protein), and
      by using minigenome assays we showed that the mutant polymerases were better
      adapted to recognizing the mutant UTRs. We suggest that deletions within the UTRs
      should be incorporated along with other specific mutations, including deletion of
      the major virulence gene encoding the NSs protein and introduction of temperature
      sensitive mutations, in the design of attenuated bunyaviruses that could have
      potential as vaccines.

PMID- 25609820
TI  - Modulation of a pore in the capsid of JC polyomavirus reduces infectivity and
      prevents exposure of the minor capsid proteins.
AB  - JC polyomavirus (JCPyV) infection of immunocompromised individuals results in the
      fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). The
      viral capsid of JCPyV is composed primarily of the major capsid protein virus
      protein 1 (VP1), and pentameric arrangement of VP1 monomers results in the
      formation of a pore at the 5-fold axis of symmetry. While the presence of this
      pore is conserved among polyomaviruses, its functional role in infection or
      assembly is unknown. Here, we investigate the role of the 5-fold pore in assembly
      and infection of JCPyV by generating a panel of mutant viruses containing amino
      acid substitutions of the residues lining this pore. Multicycle growth assays
      demonstrated that the fitness of all mutants was reduced compared to that of the
      wild-type virus. Bacterial expression of VP1 pentamers containing substitutions
      to residues lining the 5-fold pore did not affect pentamer assembly or prevent
      association with the VP2 minor capsid protein. The X-ray crystal structures of
      selected pore mutants contained subtle changes to the 5-fold pore, and no other
      changes to VP1 were observed. Pore mutant pseudoviruses were not deficient in
      assembly, packaging of the minor capsid proteins, or binding to cells or in
      transport to the host cell endoplasmic reticulum. Instead, these mutant viruses
      were unable to expose VP2 upon arrival to the endoplasmic reticulum, a step that
      is critical for infection. This study demonstrated that the 5-fold pore is an
      important structural feature of JCPyV and that minor modifications to this
      structure have significant impacts on infectious entry. IMPORTANCE: JCPyV is an
      important human pathogen that causes a severe neurological disease in
      immunocompromised individuals. While the high-resolution X-ray structure of the
      major capsid protein of JCPyV has been solved, the importance of a major
      structural feature of the capsid, the 5-fold pore, remains poorly understood.
      This pore is conserved across polyomaviruses and suggests either that these
      viruses have limited structural plasticity in this region or that this pore is
      important in infection or assembly. Using a structure-guided mutational approach,
      we showed that modulation of this pore severely inhibits JCPyV infection. These
      mutants do not appear deficient in assembly or early steps in infectious entry
      and are instead reduced in their ability to expose a minor capsid protein in the
      host cell endoplasmic reticulum. Our work demonstrates that the 5-fold pore is an
      important structural feature for JCPyV.

PMID- 25609821
TI  - Simian retrovirus 4 induces lethal acute thrombocytopenia in Japanese macaques.
AB  - In 2001-2002, six of seven Japanese macaques (Macaca fuscata) died after
      developing hemorrhagic syndrome at the Kyoto University Primate Research
      Institute (KUPRI). While the cause of death was unknown at the time, we detected
      simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak in 2008
      2011, during which 42 of 43 Japanese macaques died after exhibiting hemorrhagic
      syndrome. In this study, we isolated SRV-4 strain PRI-172 from a Japanese macaque
      showing severe thrombocytopenia. When inoculated into four Japanese macaques, the
      isolate induced severe thrombocytopenia in all within 37 days. We then
      constructed an infectious molecular clone of strain PRI-172, termed pSR415, and
      inoculated the clone-derived virus into two Japanese macaques. These animals also
      developed severe thrombocytopenia in just 31 days after inoculation, and the
      virus was reisolated from blood, bone marrow, and stool. At necropsy, we observed
      bleeding from the gingivae and subcutaneous bleeding in all animals. SRV-4
      infected a variety of tissues, especially in digestive organs, including colon
      and stomach, as determined by real-time reverse transcription-PCR (RT-PCR) and
      immunohistochemical staining. Furthermore, we identified the SRV-4 receptor as
      ASCT2, a neutral amino acid transporter. ASCT2 mRNA was expressed in a variety of
      tissues, and the distribution of SRV-4 proviruses in infected Japanese macaques
      correlated well with the expression levels of ASCT2 mRNA. From these results, we
      conclude that the causative agent of hemorrhagic syndrome in KUPRI Japanese
      macaques was SRV-4, and its receptor is ASCT2. IMPORTANCE: During two separate
      outbreaks at the KUPRI, in 2001-2002 and 2008-2011, 96% of Japanese macaques (JM)
      that developed an unknown hemorrhagic syndrome died. Here, we isolated SRV-4 from
      a JM developing thrombocytopenia. The SRV-4 isolate and a molecularly cloned SRV
      4 induced severe thrombocytopenia in virus-inoculated JMs within 37 days. At
      necropsy, we observed bleeding from gingivae and subcutaneous bleeding in all
      affected JMs and reisolated SRV-4 from blood, bone marrow, and stool. The
      distribution of SRV-4 proviruses in tissues correlated with the mRNA expression
      levels of ASCT2, which we identified as the SRV-4 receptor. From these results,
      we conclude that SRV-4 was the causative agent of hemorrhagic syndrome in JMs in
      KUPRI.

PMID- 25609822
TI  - Complete genome sequence of Pig-tailed macaque rhadinovirus 2 and its
      evolutionary relationship with rhesus macaque rhadinovirus and human herpesvirus
      8/Kaposi's sarcoma-associated herpesvirus.
AB  - Two rhadinovirus lineages have been identified in Old World primates. The
      rhadinovirus 1 (RV1) lineage consists of human herpesvirus 8, Kaposi's sarcoma
      associated herpesvirus (KSHV), and closely related rhadinoviruses of chimpanzees,
      gorillas, macaques and other Old World primates. The RV2 rhadinovirus lineage is
      distinct and consists of closely related viruses from the same Old World primate
      species. Rhesus macaque rhadinovirus (RRV) is the RV2 prototype, and two RRV
      isolates, 26-95 and 17577, were sequenced. We determined that the pig-tailed
      macaque RV2 rhadinovirus, MneRV2, is highly associated with lymphomas in macaques
      with simian AIDS. To further study the role of rhadinoviruses in the development
      of lymphoma, we sequenced the complete genome of MneRV2 and identified 87 protein
      coding genes and 17 candidate microRNAs (miRNAs). A strong genome colinearity and
      sequence homology were observed between MneRV2 and RRV26-95, although the open
      reading frame (ORF) encoding the KSHV ORFK15 homolog was disrupted in RRV26-95.
      Comparison with MneRV2 revealed several genomic anomalies in RRV17577 that were
      not present in other rhadinovirus genomes, including an N-terminal duplication in
      ORF4 and a recombinative exchange of more distantly related homologs of the
      ORF22/ORF47 interacting glycoprotein genes. The comparison with MneRV2 has
      revealed novel genes and important conservation of protein coding domains and
      transcription initiation, termination, and splicing signals, which have added to
      our knowledge of RV2 rhadinovirus genetics. Further comparisons with KSHV and
      other RV1 rhadinoviruses will provide important avenues for dissecting the
      biology, evolution, and pathology of these closely related tumor-inducing viruses
      in humans and other Old World primates. IMPORTANCE: This work provides the
      sequence characterization of MneRV2, the pig-tailed macaque homolog of rhesus
      rhadinovirus (RRV). MneRV2 and RRV belong to the rhadinovirus 2 (RV2)
      rhadinovirus lineage of Old World primates and are distinct but related to
      Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's
      sarcoma. Pig-tailed macaques provide important models of human disease, and our
      previous studies have indicated that MneRV2 plays a causal role in AIDS-related
      lymphomas in macaques. Delineation of the MneRV2 sequence has allowed a detailed
      characterization of the genome structure, and evolutionary comparisons with RRV
      and KSHV have identified conserved promoters, splice junctions, and novel genes.
      This comparison provides insight into RV2 rhadinovirus biology and sets the
      groundwork for more intensive next-generation (Next-Gen) transcript and genetic
      analysis of this class of tumor-inducing herpesvirus. This study supports the use
      of MneRV2 in pig-tailed macaques as an important model for studying rhadinovirus
      biology, transmission and pathology.

PMID- 25609823
TI  - Soluble T cell immunoglobulin mucin domain 3 is shed from CD8+ T cells by the
      sheddase ADAM10, is increased in plasma during untreated HIV infection, and
      correlates with HIV disease progression.
AB  - Chronic HIV infection results in a loss of HIV-specific CD8(+) T cell effector
      function, termed "exhaustion," which is mediated, in part, by the membrane
      coinhibitory receptor T cell immunoglobulin mucin domain-3 (Tim-3). Like many
      other receptors, a soluble form of this protein has been described in human blood
      plasma. However, soluble Tim-3 (sTim-3) is poorly characterized, and its role in
      HIV disease is unknown. Here, we show that Tim-3 is shed from the surface of
      responding CD8(+) T cells by the matrix metalloproteinase ADAM10, producing a
      soluble form of the coinhibitory receptor. Despite previous reports in the mouse
      model, no alternatively spliced, soluble form of Tim-3 was observed in humans.
      Shed sTim-3 was found in human plasma and was significantly elevated during early
      and chronic untreated HIV infection, but it was not found differentially
      modulated in highly active antiretroviral therapy (HAART)-treated HIV-infected
      subjects or in elite controllers compared to HIV-uninfected subjects. Plasma sTim
      3 levels were positively correlated with HIV load and negatively correlated with
      CD4 counts. Thus, plasma sTim-3 shedding correlated with HIV disease progression.
      Despite these correlations, we found that shedding Tim-3 did not improve the
      function of CD8(+) T cells in terms of gamma interferon production or prevent
      their apoptosis through galectin-9. Further characterization studies of sTim-3
      function are needed to understand the contribution of sTim-3 in HIV disease
      pathogenesis, with implications for novel therapeutic interventions. IMPORTANCE:
      Despite the overall success of HAART in slowing the progression to AIDS in HIV
      infected subjects, chronic immune activation and T cell exhaustion contribute to
      the eventual deterioration of the immune system. Understanding these processes
      will aid in the development of interventions and therapeutics to be used in
      combination with HAART to slow or reverse this deterioration. Here, we show that
      a soluble form of T cell exhaustion associated coinhibitory molecule 3, sTim-3,
      is shed from the surface of T cells. Furthermore, sTim-3 is elevated in the
      plasma of treatment-naive subjects with acute or chronic HIV infection and is
      associated with markers of disease progression. This is the first study to
      characterize sTim-3 in human plasma, its source, and mechanism of production.
      While it is still unclear whether sTim-3 contributes to HIV pathogenesis, sTim-3
      may represent a new correlate of HIV disease progression.

PMID- 25609824
TI  - Tracking synthesis and turnover of triacylglycerol in leaves.
AB  - Triacylglycerol (TAG), typically represents <1% of leaf glycerolipids but can
      accumulate under stress and other conditions or if leaves are supplied with fatty
      acids, or in plants transformed with regulators or enzymes of lipid metabolism.
      To better understand the metabolism of TAG in leaves, pulse-chase radiolabelling
      experiments were designed to probe its synthesis and turnover. When Arabidopsis
      leaves were incubated with [(14)C]lauric acid (12:0), a major initial product was
      [(14)C]TAG. Thus, despite low steady-state levels, leaves possess substantial TAG
      biosynthetic capacity. The contributions of diacylglycerol acyltransferase1 and
      phospholipid:diacylglycerol acyltransferase1 to leaf TAG synthesis were examined
      by labelling of dgat1 and pdat1 mutants. The dgat1 mutant displayed a major (76%)
      reduction in [(14)C]TAG accumulation whereas pdat1 TAG labelling was only
      slightly reduced. Thus, DGAT1 has a principal role in TAG biosynthesis in young
      leaves. During a 4h chase period, radioactivity in TAG declined 70%, whereas the
      turnover of [(14)C]acyl chains of phosphatidylcholine (PC) and other polar lipids
      was much lower. Sixty percent of [(14)C]12:0 was directly incorporated into
      glycerolipids without modification, whereas 40% was elongated and desaturated to
      16:0 and 18:1 by plastids. The unmodified [(14)C]12:0 and the plastid products of
      [(14)C]12:0 metabolism entered different pathways. Although plastid-modified
      (14)C-labelled products accumulated in monogalactosyldiacylglycerol, PC,
      phosphatidylethanolamine, and diacylglcerol (DAG), there was almost no
      accumulation of [(14)C]16:0 and [(14)C]18:1 in TAG. Because DAG and acyl-CoA are
      direct precursors of TAG, the differential labelling of polar glycerolipids and
      TAG by [(14)C]12:0 and its plastid-modified products provides evidence for
      multiple subcellular pools of both acyl-CoA and DAG. 

PMID- 25609825
TI  - Arabidopsis response to low-phosphate conditions includes active changes in actin
      filaments and PIN2 polarization and is dependent on strigolactone signalling.
AB  - Strigolactones (SLs) are plant hormones that regulate the plant response to
      phosphate (Pi) growth conditions. At least part of SL-signalling execution in
      roots involves MAX2-dependent effects on PIN2 polar localization in the plasma
      membrane (PM) and actin bundling and dynamics. We examined PIN2 expression, PIN2
      PM localization, endosome trafficking, and actin bundling under low-Pi
      conditions: a MAX2-dependent reduction in PIN2 trafficking and polarization in
      the PM, reduced endosome trafficking, and increased actin-filament bundling were
      detected in root cells. The intracellular protein trafficking that is related to
      PIN proteins but unassociated with AUX1 PM localization was selectively
      inhibited. Exogenous supplementation of the synthetic SL GR24 to a SL-deficient
      mutant (max4) led to depletion of PIN2 from the PM under low-Pi conditions.
      Accordingly, roots of mutants in MAX2, MAX4, PIN2, TIR3, and ACTIN2 showed a
      reduced low-Pi response compared with the wild type, which could be restored by
      auxin (for all mutants) or GR24 (for all mutants except max2-1). Changes in PIN2
      polarity, actin bundling, and vesicle trafficking may be involved in the response
      to low Pi in roots, dependent on SL/MAX2 signalling. 

PMID- 25609826
TI  - Control of patterning, growth, and differentiation by floral organ identity
      genes.
AB  - In spite of the different morphologies of sepals, petals, stamens, and carpels,
      all these floral organs are believed to be modified versions of a ground-state
      organ similar to the leaf. Modifications of the ground-state developmental
      programme are orchestrated by different combinations of MADS-domain transcription
      factors encoded by floral organ identity genes. In recent years, much has been
      revealed about the gene regulatory networks controlled by the floral organ
      identity genes and about the genetic pathways that control leaf development. This
      review examines how floral organ identity is connected with the control of
      morphogenesis and differentiation of shoot organs, focusing on the model species
      Arabidopsis thaliana. Direct links have emerged between floral organ identity
      genes and genes involved in abaxial-adaxial patterning, organ boundary formation,
      tissue growth, and cell differentiation. In parallel, predictive models have been
      developed to explain how the activity of regulatory genes can be coordinated by
      intercellular signalling and constrained by tissue mechanics. When combined,
      these advances provide a unique opportunity for revealing exactly how leaf-like
      organs have been 'metamorphosed' into floral organs during evolution and showing
      crucial regulatory points in the generation of plant form. 

PMID- 25609827
TI  - Plant membrane assays with cytokinin receptors underpin the unique role of free
      cytokinin bases as biologically active ligands.
AB  - Cytokinin receptors play a key role in cytokinin-dependent processes regulating
      plant growth, development, and adaptation; therefore, the functional properties
      of these receptors are of great importance. Previously the properties of
      cytokinin receptors were investigated in heterologous assay systems using
      unicellular microorganisms, mainly bacteria, expressing receptor proteins.
      However, within microorganisms receptors reside in an alien environment that
      might distort the receptor properties. Therefore, a new assay system has been
      developed allowing studies of individual receptors within plant membranes (i.e.
      closer to their natural environment). The main ligand-binding characteristics of
      receptors from Arabidopsis [AHK2, AHK3, and AHK4] and maize (ZmHK1) were refined
      in this new system, and the properties of full-length Arabidopsis receptor AHK2
      were characterized for the first time. Ligand specificity profiles of receptors
      towards cytokinin bases were comparable with the profiles retrieved in bacterial
      assay systems. In contrast, cytokinin-9-ribosides displayed a strongly reduced
      affinity for receptors in the plant assay system, indicating that ribosides as
      the common transport form of cytokinins have no or very weak cytokinin activity.
      This underpins the central role of free bases as the sole biologically active
      cytokinin compounds. According to molecular modelling and docking studies, N (9)
      ribosylation alters the bonding pattern in cytokinin-receptor interaction and
      prevents beta6-beta7 loop movement important for tight hormone binding. A common
      feature of all receptors was a greatly reduced ligand binding at low (5.0-5.5)
      pH. The particularly high sensitivity of ZmHK1 to pH changes leads to the
      suggestion that some cytokinin receptors may play an additional role as pH
      sensors in the lumen of the endoplasmic reticulum. 

PMID- 25609829
TI  - Intronic regions of plant genes potentially encode RDR (RNA-dependent RNA
      polymerase)-dependent small RNAs.
AB  - Recent research has linked the non-coding intronic regions of plant genes to the
      production of small RNAs (sRNAs). Certain introns, called 'mirtrons' and
      'sirtrons', could serve as the single-stranded RNA precursors for the generation
      of microRNA and small interfering RNA, respectively. However, whether the
      intronic regions could serve as the template for double-stranded RNA synthesis
      and then for sRNA biogenesis through an RDR (RNA-dependent RNA polymerase)
      dependent pathway remains unclear. In this study, a genome-wide search was made
      for the RDR-dependent sRNA loci within the intronic regions of the Arabidopsis
      genes. Hundreds of intronic regions encoding three or more RDR-dependent sRNAs
      were found to be covered by dsRNA-seq (double-stranded RNA sequencing) reads,
      indicating that the intron-derived sRNAs were indeed generated from long double
      stranded RNA precursors. More interestingly, phase-distributed sRNAs were
      discovered on some of the dsRNA-seq read-covered intronic regions, and those
      sRNAs were largely 24 nt in length. Based on these results, the opinion is put
      forward that the intronic regions might serve as the genomic origins for the RDR
      dependent sRNAs. This opinion might add a novel layer to the current biogenesis
      model of the intron-derived sRNAs. 

PMID- 25609828
TI  - GhCFE1A, a dynamic linker between the ER network and actin cytoskeleton, plays an
      important role in cotton fibre cell initiation and elongation.
AB  - Fibre cell initiation and elongation is critical for cotton fibre development.
      However, little is known about the regulation of initiation and elongation during
      fibre cell development. Here, the regulatory role of a novel protein GhCFE1A was
      uncovered. GhCFE1A is preferentially expressed at initiation and rapid elongation
      stages during fibre development; in addition, much higher expression of GhCFE1A
      was detected at the fibre initiation stage in fibreless cotton mutants than in
      the fibre-bearing TM-1 wild-type. Importantly, overexpression of GhCFE1A in
      cotton not only delayed fibre cell elongation but also significantly reduced the
      density of lint and fuzz fibre initials and stem trichomes. Yeast two-hybrid
      assay showed that GhCFE1A interacted with several actin proteins, and the
      interaction was further confirmed by co-sedimentation assay. Interestingly, a
      subcellular localization assay showed that GhCFE1A resided on the cortical
      endoplasmic reticulum (ER) network and co-localized with actin cables. Moreover,
      the density of F-actin filaments was shown to be reduced in GhCFE1A
      overexpressing fibres at the rapid elongation stage compared with the wild-type
      control. Taken together, the results demonstrate that GhCFE1A probably functions
      as a dynamic linker between the actin cytoskeleton and the ER network, and plays
      an important role in fibre cell initiation and elongation during cotton fibre
      development. 

PMID- 25609830
TI  - Maternal control of seed size in plants.
AB  - Seed size is a key determinant of evolutionary fitness, and is also one of the
      most important components of seed yield. In angiosperms, seed development begins
      with double fertilization, which leads to the formation of a diploid embryo and a
      triploid endosperm. The outermost layer of the seed is the seed coat, which
      differentiates from maternal integuments. Therefore, the size of a seed is
      determined by the co-ordinated growth of the embryo, endosperm, and maternal
      tissue. Recent studies have identified several factors that act maternally or
      zygotically to regulate seed size, and revealed possible mechanisms that underlie
      seed size control in Arabidopsis and rice. In this review, we summarize current
      research progress in maternal control of seed size and discuss the roles of
      several newly identified regulators in maternal regulation of seed growth. 

PMID- 25609832
TI  - A social insect fertility signal is dependent on chemical context.
AB  - Identifying group members and individuals' status within a group are fundamental
      tasks in animal societies. For ants, this information is coded in the cuticular
      hydrocarbon profile. We manipulated profiles of the ant Odontomachus brunneus to
      examine whether the releaser and primer effects of fertility signals are
      dependent on chemical context. Fertility status is signalled through increased
      abundance of (Z)-9-nonacosene (Z9 : C29). Across the ant's distribution,
      populations have distinct hydrocarbon profiles but the fertility signal is
      conserved. Foreign queens and fertility-signal-treated workers from the same
      population, sharing a similar chemical background, elicited releaser effects from
      workers, whereas queens and fertility-signal-treated workers from different
      populations did not. Z9 : C29 presented without chemical background did not
      elicit releaser effects. A primer-effect experiment found that Z9 : C29,
      presented without a chemical background, did not inhibit worker reproduction. Our
      results demonstrate that a familiar chemical background is necessary for
      appropriate responses to fertility signals. 

PMID- 25609831
TI  - Functional and phylogenetic characterization of proteins detected in various
      nematode intestinal compartments.
AB  - The parasitic nematode intestine is responsible for nutrient digestion and
      absorption, and many other processes essential for reproduction and survival,
      making it a valuable target for anthelmintic drug treatment. However, nematodes
      display extreme biological diversity (including occupying distinct trophic
      habitats), resulting in limited knowledge of intestinal cell/protein functions of
      fundamental or adaptive significance. We developed a perfusion model for
      isolating intestinal proteins in Ascaris suum (a parasite of humans and swine),
      allowing for the identification of over 1000 intestinal A. suum proteins (using
      mass spectrometry), which were assigned to several different intestinal cell
      compartments (intestinal tissue, the integral and peripheral intestinal
      membranes, and the intestinal lumen). A multi-omics analysis approach identified
      a large diversity of biological functions across intestinal compartments, based
      on both functional enrichment analysis (identifying terms related to
      detoxification, proteolysis, and host-parasite interactions) and regulatory
      binding sequence analysis to identify putatively active compartment-specific
      transcription factors (identifying many related to intestinal sex differentiation
      or lifespan regulation). Orthologs of A. suum proteins in 15 other nematodes
      species, five host species, and two outgroups were identified and analyzed.
      Different cellular compartments demonstrated markedly different levels of protein
      conservation; e.g. integral intestinal membrane proteins were the most conserved
      among nematodes (up to 96% conservation), whereas intestinal lumen proteins were
      the most diverse (only 6% conservation across all nematodes, and 71% with no host
      orthologs). Finally, this integrated multi-omics analysis identified conserved
      nematode-specific intestinal proteins likely performing essential functions
      (including V-type ATPases and ABC transporters), which may serve as promising
      anthelmintic drug or vaccine targets in future research. Collectively, the
      findings provide valuable new insights on conserved and adaptive features of
      nematode intestinal cells, membranes and the intestinal lumen, and potential
      targets for parasite treatment and control. 

PMID- 25609833
TI  - Dexrazoxane abrogates acute doxorubicin toxicity in marmoset ovary.
AB  - Preservation of ovarian function following chemotherapy for nonovarian cancers is
      a formidable challenge. For prepubescent girls, the only option to prevent
      chemotherapy damage to the ovary is ovarian tissue cryopreservation, an
      experimental procedure requiring invasive surgeries to harvest and reimplant
      tissue, which carries the risk of cancer reintroduction. Drugs that block the
      primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the
      context of anthracycline chemotherapy, provide a novel approach for ovarian
      protection and have the potential to overcome current limitations to
      oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that
      protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in
      vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation.
      To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman
      primate, freshly obtained marmoset ovarian tissue was cultured in vitro and
      treated with vehicle or 20 MUM Dexra 1 h prior to 50 nM DXR. Cultured ovarian
      tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR
      induced DNA double-strand breaks as quantified by the neutral comet assay. DXR
      treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing
      the number of foci-positive granulosa cells in antral follicles, while Dexra
      pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation.
      Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1
      phosphorylation and caspase-9 activation as assayed by Western blots of ovarian
      tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced
      DNA damage, the subsequent cellular response to DNA damage, and may diminish
      early apoptotic signaling in marmoset ovarian tissue. This study provides initial
      translation of Dexra protection against acute ovarian DXR toxicity from mice to
      marmoset monkey tissue. 

PMID- 25609835
TI  - The forebrain-midbrain acts as functional endocrine signaling pathway of
      Kiss2/Gnrh1 system controlling the gonadotroph activity in the teleost fish
      European sea bass (Dicentrarchus labrax).
AB  - Some teleost species, including European sea bass, harbor two different
      kisspeptin coding genes: kiss1 and kiss2. Both genes are expressed in the brain,
      but their differential roles in the central control of fish reproduction are only
      beginning to be elucidated. In this study, we have examined the effects of
      intracerebroventricular injections of the highly active sea bass peptides Kiss1
      15 and Kiss2-12 on spermiating male sea bass. Physiological saline, Kiss1-15, or
      Kiss2-12 was injected into the third ventricle. To establish the gene expression
      cascade involved in the action of kisspeptins, the expression of the two sea bass
      kisspeptin receptor genes (kiss1r and kiss2r) and the three sea bass Gnrh genes
      (gnrh1, gnrh2, and gnrh3) were analyzed in the forebrain-midbrain and the
      hypothalamus. In addition, the protein levels of hypothalamic and pituitary Gnrh1
      were measured. Blood samples were collected at different times after injection to
      analyze the effects of kisspeptins on the release of gonadotropins (Lh and Fsh)
      and androgens (testosterone and 11-ketotestosterone). The present results provide
      the first evidence that the effects of Kiss2 on central regulation of
      reproductive function involve the neuroendocrine areas of the forebrain-midbrain
      in teleost fish. The marked effect of Kiss2 on kiss2r and gnrh1 expression in the
      forebrain-midbrain and on Gnrh1 release suggest that this neuronal system is
      involved in the neuroendocrine regulation of gonadotroph activity. This
      hypothesis was confirmed by a surge of plasma Lh in response to Kiss2, which
      presumably has a strong stimulatory effect on testosterone release, and thus on
      sperm quality parameters. 

PMID- 25609834
TI  - Impairment of preimplantation porcine embryo development by histone demethylase
      KDM5B knockdown through disturbance of bivalent H3K4me3-H3K27me3 modifications.
AB  - KDM5B (JARID1B/PLU1) is a H3K4me2/3 histone demethylase that is implicated in
      cancer development and proliferation and is also indispensable for embryonic stem
      cell self-renewal, cell fate, and murine embryonic development. However, little
      is known about the role of KDM5B during preimplantation embryo development. Here
      we show that KDM5B is critical to porcine preimplantation development. KDM5B was
      found to be expressed in a stage-specific manner, consistent with demethylation
      of H3K4me3, with the highest expression being observed from the 4-cell to the
      blastocyst stages. Knockdown of KDM5B by morpholino antisense oligonucleotides
      injection impaired porcine embryo development to the blastocyst stage. The
      impairment of embryo development might be caused by increased expression of
      H3K4me3 at the 4-cell and blastocyst stages, which disturbs the balance of
      bivalent H3K4me3-H3K27me3 modifications at the blastocyst stage. Decreased
      abundance of H3K27me3 at blastocyst stage activates multiple members of homeobox
      genes (HOX), which need to be silenced for faithful embryo development.
      Additionally, the histone demethylase KDM6A was found to be upregulated by
      knockdown of KDM5B, which indicated it was responsible for the decreased
      abundance of H3K27me3 at the blastocyst stage. The transcriptional levels of Ten
      Eleven Translocation gene family members (TET1, TET2, and TET3) are found to be
      increased by knockdown of KDM5B, which indicates cross talk between histone
      modifications and DNA methylation. The studies above indicate that KDM5B is
      required for porcine embryo development through regulating the balance of
      bivalent H3K4me3-H3K27me3 modifications. 

PMID- 25609836
TI  - The catecholestrogen, 2-hydroxyestradiol-17beta, acts as a G protein-coupled
      estrogen receptor 1 (GPER/GPR30) antagonist to promote the resumption of meiosis
      in zebrafish oocytes.
AB  - Estradiol-17beta (E2) maintains high cAMP levels and meiotic arrest in zebrafish
      oocytes through activation of G protein-coupled estrogen receptor (GPER). The
      catecholestrogen 2-hydroxyestradiol-17beta (2-OHE2) has an opposite effect to
      that of E2 on oocyte maturation (OM) and cAMP levels in Indian catfish oocytes.
      We tested the hypothesis that 2-OHE2 is produced in zebrafish ovaries and
      promotes the resumption of oocyte meiosis through its action as a GPER
      antagonist. Ovarian 2-OHE2 production by estrogen-2-hydroxylase (EH) was up
      regulated by gonadotropin treatment at the onset of OM, consistent with a
      physiological role for 2-OHE2 in regulating OM. The increases in EH activity and
      OM were blocked by treatment with CYP1A1 and CYP1B1 inhibitors. Expression of
      cyp1a, cyp1b1, and cyp1c mRNAs was increased by gonadotropin treatment, further
      implicating these Cyp1s in 2-OHE2 synthesis prior to OM. Conversely, aromatase
      activity and cyp19a1 mRNA expression declined during gonadotropin induction of
      OM. 2-OHE2 treatment significantly increased spontaneous OM in defolliculated
      zebrafish oocytes and reversed the inhibition of OM by E2 and the GPER agonist G
      1. 2-OHE2 was an effective competitor of [(3)H]-E2 binding to recombinant
      zebrafish GPER expressed in HEK-293 cells. 2-OHE2 also antagonized estrogen
      actions through GPER on cAMP production in zebrafish oocytes, resulting in a
      reduction in cAMP levels. Stimulation of OM by 2-OHE2 was blocked by pretreatment
      of defolliculated oocytes with the GPER antibody. Collectively, the results
      suggest that 2-OHE2 functions as a GPER antagonist and promotes OM in zebrafish
      through blocking GPER-dependent E2 inhibition of the resumption of OM. 

PMID- 25609837
TI  - Deficiency of CDKN1A or both CDKN1A and CDKN1B affects the pubertal development
      of mouse Leydig cells.
AB  - Cyclin-dependent kinase inhibitors p21(Cip1) (CDKN1A) and p27(Kip1) (CDKN1B) are
      expressed in Leydig cells. Previously, we reported that Cdkn1b knockout in the
      mouse led to increased Leydig cell proliferative capacity and lower
      steroidogenesis. However, the relative importance of CDKN1A and CDKN1B in these
      regulations was unclear. In the present study, we examined the relative
      importance of CDKN1A and CDKN1B in regulation of Leydig cell proliferation and
      steroidogenesis by whole-body knockout of CDKN1A (Cdkn1a(-/-)) and CDKN1A/CDKN1B
      double knockout (DBKO). The cell number, 5-bromo-2-deoxyuridine incorporation
      rate, steroidogenesis, and steroidogenic enzyme mRNA levels and activities of
      Leydig cells were compared among wild-type (WT), Cdkn1a(-/-), and DBKO mice.
      Relative to WT mice, Leydig cell number per testis was doubled in the DBKO and
      unchanged in the Cdkn1a(-/-) mice. Testicular testosterone levels and mRNA levels
      for luteinizing hormone receptor (Lhcgr), steroidogenic acute regulatory protein
      (Star), cholesterol side-chain cleavage enzyme (Cyp11a1), 17alpha
      hydroxylase/17,20-lyase (Cyp17a1), and 17beta-hydroxysteroid dehydrogenase 3
      (Hsd17b3) and their respective proteins were significantly lower in the DBKO
      mice. However, testicular testosterone level was unchanged in the Cdkn1a(-/-)
      mice, although Lhcgr mRNA levels were significantly lower relative to those in
      the WT control. We conclude that Cdkn1a(-/-) did not increase Leydig cell numbers
      (although a defect of Leydig cell function was noted), whereas DBKO caused a
      significant increase of Leydig cell numbers but a decrease of steroidogenesis. 

PMID- 25609838
TI  - Combining RNA and protein profiling data with network interactions identifies
      genes associated with spermatogenesis in mouse and human.
AB  - Genome-wide RNA profiling studies have identified hundreds of transcripts that
      are highly expressed in mammalian male germ cells, including many that are
      undetectable in somatic control tissues. Among them, genes important for
      spermatogenesis are significantly enriched. Information about mRNAs and their
      cognate proteins facilitates the identification of novel conserved target genes
      for functional studies in the mouse. By inspecting genome-wide RNA profiling
      data, we manually selected 81 genes for which RNA is detected almost exclusively
      in the human male germline and, in most cases, in rodent testicular germ cells.
      We observed corresponding mRNA/protein patterns in 43 cases using
      immunohistochemical data from the Human Protein Atlas and large-scale human
      protein profiling data obtained via mass spectroscopy. Protein network
      information enabled us to establish an interaction map of 38 proteins that points
      to potentially important testicular roles for some of them. We further
      characterized six candidate genes at the protein level in the mouse. We conclude
      that conserved genes induced in testis tend to show similar mRNA/protein
      expression patterns across species. Specifically, our results suggest roles
      during embryogenesis and adult spermatogenesis for Foxr1 and Sox30 and during
      spermiogenesis and fertility for Fam71b, 1700019N19Rik, Hmgb4, and Zfp597. 

PMID- 25609840
TI  - PP6 controls T cell development and homeostasis by negatively regulating distal
      TCR signaling.
AB  - T cell development and homeostasis are both regulated by TCR signals. Protein
      phosphorylation and dephosphorylation, which are catalyzed by protein kinases and
      phosphatases, respectively, serve as important switches controlling multiple
      downstream pathways triggered by TCR recognition of Ags. It has been well
      documented that protein tyrosine phosphatases are involved in negative regulation
      of proximal TCR signaling. However, how TCR signals are terminated or attenuated
      in the distal TCR signaling pathways is largely unknown. We investigated the
      function of Ser/Thr protein phosphatase (PP) 6 in TCR signaling. T cell lineage
      specific ablation of PP6 in mice resulted in enhanced thymic positive and
      negative selection, and preferential expansion of fetal-derived, IL-17-producing
      Vgamma6Vdelta1(+) T cells. Both PP6-deficient peripheral CD4(+) helper and CD8(+)
      cytolytic cells could not maintain a naive state and became fast-proliferating
      and short-lived effector cells. PP6 deficiency led to profound hyperactivation of
      multiple distal TCR signaling molecules, including MAPKs, AKT, and NF-kappaB. Our
      studies demonstrate that PP6 acts as a critical negative regulator, not only
      controlling both alphabeta and gammadelta lineage development, but also
      maintaining naive T cell homeostasis by preventing their premature activation
      before Ag stimulation. 

PMID- 25609839
TI  - Barcoding of live human peripheral blood mononuclear cells for multiplexed mass
      cytometry.
AB  - Mass cytometry is developing as a means of multiparametric single-cell analysis.
      In this study, we present an approach to barcoding separate live human PBMC
      samples for combined preparation and acquisition on a cytometry by time of flight
      instrument. Using six different anti-CD45 Ab conjugates labeled with Pd104,
      Pd106, Pd108, Pd110, In113, and In115, respectively, we barcoded up to 20 samples
      with unique combinations of exactly three different CD45 Ab tags. Cell events
      carrying more than or less than three different tags were excluded from analyses
      during Boolean data deconvolution, allowing for precise sample assignment and the
      electronic removal of cell aggregates. Data from barcoded samples matched data
      from corresponding individually stained and acquired samples, at cell event
      recoveries similar to individual sample analyses. The approach greatly reduced
      technical noise and minimizes unwanted cell doublet events in mass cytometry
      data, and it reduces wet work and Ab consumption. It also eliminates sample-to
      sample carryover and the requirement of instrument cleaning between samples,
      thereby effectively reducing overall instrument runtime. Hence, CD45 barcoding
      facilitates accuracy of mass cytometric immunophenotyping studies, thus
      supporting biomarker discovery efforts, and it should be applicable to
      fluorescence flow cytometry as well. 

PMID- 25609841
TI  - Recombinant thrombomodulin inhibits lipopolysaccharide-induced inflammatory
      response by blocking the functions of CD14.
AB  - CD14, a multiligand pattern-recognition receptor, is involved in the activation
      of many TLRs. Thrombomodulin (TM), a type I transmembrane glycoprotein,
      originally was identified as an anticoagulant factor that activates protein C.
      Previously, we showed that the recombinant TM lectin-like domain binds to LPS and
      inhibits LPS-induced inflammation, but the function of the recombinant epidermal
      growth factor-like domain plus serine/threonine-rich domain of TM (rTMD23) in LPS
      induced inflammation remains unknown. In the current study, we found that rTMD23
      markedly suppressed the activation of intracellular signaling pathways and the
      production of inflammatory cytokines induced by LPS. The anti-inflammatory
      activity of rTMD23 was independent of activated protein C. We also found that
      rTMD23 interacted with the soluble and membrane forms of CD14 and inhibited the
      CD14-mediated inflammatory response. Knockdown of CD14 in macrophages suppressed
      the production of inflammatory cytokines induced by LPS, and rTMD23 inhibited LPS
      induced IL-6 production in CD14-knockdown macrophages. rTMD23 suppressed the
      binding of LPS to macrophages by blocking the association between monocytic
      membrane-bound TM and CD14. The administration of rTMD23 in mice, both
      pretreatment and posttreatment, significantly increased the survival rate and
      reduced the inflammatory response to LPS. Notably, the serine/threonine-rich
      domain is essential for the anti-inflammatory activity of rTMD23. To summarize,
      we show that rTMD23 suppresses the LPS-induced inflammatory response in mice by
      targeting CD14 and that the serine/threonine-rich domain is crucial for the
      inhibitory effect of rTMD23 on LPS-induced inflammation. 

PMID- 25609842
TI  - Neutrophil IL-1beta processing induced by pneumolysin is mediated by the
      NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux.
AB  - Although neutrophils are the most abundant cells in acute infection and
      inflammation, relatively little attention has been paid to their role in
      inflammasome formation and IL-1beta processing. In the present study, we
      investigated the mechanism by which neutrophils process IL-1beta in response to
      Streptococcus pneumoniae. Using a murine model of S. pneumoniae corneal
      infection, we demonstrated a requirement for IL-1beta in bacterial clearance, and
      we showed that Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck
      like protein containing a caspase activation and recruitment domain (ASC), and
      caspase-1 are essential for IL-1beta production and bacterial killing in the
      cornea. Neutrophils in infected corneas had multiple specks with enzymatically
      active caspase-1 (YVAD-FLICA 660), and bone marrow neutrophils stimulated with
      heat-killed S. pneumoniae (signal 1) and pneumolysin (signal 2) exhibited
      multiple specks when stained for NLRP3, ASC, or Caspase-1. High-molecular mass
      ASC complexes were also detected, consistent with oligomer formation. Pneumolysin
      induced K(+) efflux in neutrophils, and blocking K(+) efflux inhibited caspase-1
      activation and IL-1beta processing; however, neutrophils did not undergo
      pyroptosis, indicating that K(+) efflux and IL-1beta processing is not a
      consequence of cell death. There was also no role for lysosomal destabilization
      or neutrophil elastase in pneumolysin-mediated IL-1beta processing in
      neutrophils. Taken together, these findings demonstrate an essential role for
      neutrophil-derived IL-1beta in S. pneumoniae infection, and they elucidate the
      role of the NLRP3 inflammasome in cleavage and secretion of IL-1beta in
      neutrophils. Given the ubiquitous presence of neutrophils in acute bacterial and
      fungal infections, these findings will have implications for other microbial
      diseases. 

PMID- 25609843
TI  - Positive feedback regulation of type I IFN production by the IFN-inducible DNA
      sensor cGAS.
AB  - Rapid and robust induction of type I IFN (IFN-I) is a critical event in host
      antiviral innate immune response. It has been well demonstrated that cyclic GMP
      AMP (cGAMP) synthase (cGAS) plays an important role in sensing cytosolic DNA and
      triggering STING dependent signaling to induce IFN-I. However, it is largely
      unknown how cGAS itself is regulated during pathogen infection and IFN-I
      production. In this study, we show that pattern recognition receptor (PRR)
      ligands, including lipid A, LPS, poly(I:C), poly(dA:dT), and cGAMP, induce cGAS
      expression in an IFN-I-dependent manner in both mouse and human macrophages.
      Further experiments indicated that cGAS is an IFN-stimulated gene (ISG), and two
      adjacent IFN-sensitive response elements (ISREs) in the promoter region of cGAS
      mediate the induction of cGAS by IFN-I. Additionally, we show that optimal
      production of IFN-beta triggered by poly (dA:dT) or HSV-1 requires IFNAR
      signaling. Knockdown of the constitutively expressed DNA sensor DDX41 attenuates
      poly(dA:dT)-triggered IFN-beta production and cGAS induction. By analyzing the
      dynamic expression of poly(dA:dT)-induced IFN-beta and cGAS transcripts, we have
      found that induction of IFN-beta is earlier than cGAS. Furthermore, we have
      provided evidence that induction of cGAS by IFN-I meditates the subsequent
      positive feedback regulation of DNA-triggered IFN-I production. Thus, our study
      not only provides a novel mechanism of modulating cGAS expression, but also adds
      another layer of regulation in DNA-triggered IFN-I production by induction of
      cGAS. 

PMID- 25609844
TI  - Dermal-resident versus recruited gammadelta T cell response to cutaneous vaccinia
      virus infection.
AB  - The study of T cell immunity at barrier surfaces has largely focused on T cells
      bearing the alphabeta TCR. However, T cells that express the gammadelta TCR are
      disproportionately represented in peripheral tissues of mice and humans,
      suggesting they too may play an important role responding to external stimuli. In
      this article, we report that, in a murine model of cutaneous infection with
      vaccinia virus, dermal gammadelta T cell numbers increased 10-fold in the
      infected ear and resulted in a novel gammadelta T cell population not found in
      naive skin. Circulating gammadelta T cells were specifically recruited to the
      site of inflammation and differentially contributed to dermal populations based
      on their CD27 expression. Recruited gammadelta T cells, the majority of which
      were CD27(+), were granzyme B(+) and made up about half of the dermal population
      at the peak of the response. In contrast, recruited and resident gammadelta T
      cell populations that made IL-17 were CD27(-). Using a double-chimera model that
      can discriminate between the resident dermal and recruited gammadelta T cell
      populations, we demonstrated their divergent functions and contributions to early
      stages of tissue inflammation. Specifically, the loss of the perinatal thymus
      derived resident dermal population resulted in decreased cellularity and
      collateral damage in the tissue during viral infection. These findings have
      important implications for our understanding of immune coordination at barrier
      surfaces and the contribution of innate-like lymphocytes on the front lines of
      immune defense. 

PMID- 25609845
TI  - mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated
      suppression during hair regeneration.
AB  - Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen),
      and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells
      (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly
      the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1
      (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC
      activation at the telogen-to-anagen transition. By using both an inducible
      conditional gene targeting strategy and a pharmacological inhibition method to
      ablate or inhibit mTOR signaling in adult skin epithelium before anagen
      initiation, we demonstrate that HFs that cannot respond to mTOR signaling display
      significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP
      signaling activity is dramatically prolonged in mTOR signaling-deficient HFs.
      Through both gain- and loss-of-function studies in vitro, we show that mTORC1
      signaling negatively affects BMP signaling, which serves as a main mechanism
      whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression
      of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null
      skin. Our findings reveal a critical role for mTOR signaling in regulating stem
      cell activation through counterbalancing BMP-mediated repression during hair
      regeneration. 

PMID- 25609846
TI  - E-cigarettes: a disruptive technology that revolutionizes our field?

PMID- 25609851
TI  - Advantages of reaction cell ICP-MS on doubly charged interferences for arsenic
      and selenium analysis in foods.
AB  - Recent reports of As concentrations in certain food and drinks have garnered
      public concern and led to a lowering of the US guideline maximum concentration
      for inorganic As in apple juice and proposed limits for As in rice products. In
      contrast Se is an essential micro-nutrient that can be limiting when Se-poor
      soils yield Se-poor food crops. Rare earth element (REE) doubly charged
      interferences on As and Se can be significant even when initial ICP-MS tuning
      minimizes doubly charged formation. We analyzed NIST 1547 (peach leaves) and 1515
      (apple leaves), which contain high levels of REEs, by quadrupole ICP-MS with (He)
      collision mode, H2 reaction mode or triple quadrupole ICP-MS (ICP-QQQ) in mass
      shift mode (O2 and O2/H2). Analysis by collision cell ICP-MS significantly over
      estimated As and Se concentration due to REE doubly charged formation;
      mathematical correction increased the accuracy of analysis but is prone to error
      when analyte concentration and sensitivity is low and interferent is high. For
      Se, H2 reaction mode was effective in suppressing Gd2+ leading to accurate
      determination of Se in both SRMs without the need for mathematical correction.
      ICP-QQQ using mass-shift mode for As+ from m/z 75 to AsO+ at m/z 91 and Se+ from
      m/z 78 to SeO+ at m/z 94 alleviated doubly charged effects and resulted in
      accurate determination of As and Se in both SRMs without the need for correction
      equations. Zr and Mo isobars at 91 and 94 were shown to be effectively rejected
      by the MS/MS capability of the ICP-QQQ.

PMID- 25609852
TI  - High frequency of CD8 positive lymphocyte infiltration correlates with lack of
      lymph node involvement in early rectal cancer.
AB  - AIMS: A trend towards local excision of early rectal cancers has prompted us to
      investigate if immunoprofiling might help in predicting lymph node involvement in
      this subgroup. METHODS: A tissue microarray of 126 biopsies of early rectal
      cancer (T1 and T2) was stained for several immunomarkers of the innate and the
      adaptive immune response. Patients' survival and nodal status were analyzed and
      correlated with infiltration of the different immune cells. RESULTS: Of all
      tested markers, only CD8 (P = 0.005) and TIA-1 (P = 0.05) were significantly more
      frequently detectable in early rectal cancer biopsies of node negative as
      compared to node positive patients. Although these two immunomarkers did not
      display prognostic effect "per se," CD8+ and, marginally, TIA-1 T cell
      infiltration could predict nodal involvement in univariate logistic regression
      analysis (OR 0.994; 95% CI 0.992-0.996; P = 0.009 and OR 0.988; 95% CI 0.984
      0.994; P = 0.05, resp.). An algorithm significantly predicting the nodal status
      in early rectal cancer based on CD8 together with vascular invasion and tumor
      border configuration could be calculated (P < 0.00001). CONCLUSION: Our data
      indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps
      in predicting patients' nodal involvement.

PMID- 25609854
TI  - Dengue: A runaway epidemic and a bewildered public health worker.

PMID- 25609855
TI  - Joint replacement surgery in the Armed Forces Medical Services, India: The
      journey so far and looking ahead.

PMID- 25609853
TI  - Tissue damage markers after a spinal manipulation in healthy subjects: a
      preliminary report of a randomized controlled trial.
AB  - Spinal manipulation (SM) is a manual therapy technique frequently applied to
      treat musculoskeletal disorders because of its analgesic effects. It is defined
      by a manual procedure involving a directed impulse to move a joint past its
      physiologic range of movement (ROM). In this sense, to exceed the physiologic ROM
      of a joint could trigger tissue damage, which might represent an adverse effect
      associated with spinal manipulation. The present work tries to explore the
      presence of tissue damage associated with SM through the damage markers analysis.
      Thirty healthy subjects recruited at the University of Jaen were submitted to a
      placebo SM (control group; n = 10), a single lower cervical manipulation
      (cervical group; n = 10), and a thoracic manipulation (n = 10). Before the
      intervention, blood samples were extracted and centrifuged to obtain plasma and
      serum. The procedure was repeated right after the intervention and two hours
      after the intervention. Tissue damage markers creatine phosphokinase (CPK),
      lactate dehydrogenase (LDH), C-reactive protein (CRP), troponin-I, myoglobin,
      neuron-specific enolase (NSE), and aldolase were determined in samples.
      Statistical analysis was performed through a 3 * 3 mixed-model ANOVA. Neither
      cervical manipulation nor thoracic manipulation did produce significant changes
      in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our
      data suggest that the mechanical strain produced by SM seems to be innocuous to
      the joints and surrounding tissues in healthy subjects. 

PMID- 25609856
TI  - Dengue outbreak in a large military station: Have we learnt any lesson?
AB  - BACKGROUND: An outbreak was reported from a large military station located in
      South India in 2013. In spite of instituting the preventive measures early, it
      took more than 2 months to bring the outbreak under control. This paper brings
      out lessons learnt and suggests strategy for controlling similar outbreak in
      future. METHOD: The Military station comprises of 6 large Regimental Centres and
      many smaller units. The approximate strength of the serving personnel and their
      families is 25,000. Besides the unit Regimental Medical Officers, a large
      tertiary care hospital and a Station Health Organization is available to provide
      health care. RESULT: A total of 266 patients including 192 serving personnel and
      74 of their dependents were hospitalized for dengue between 15 May 2013 and 28
      Jul 2013. Many dependents not having severe symptoms, were not hospitalized and
      treated on outpatient basis. Health advisories and instructions for constituting
      Dengue Task Force (DTF) were issued well in advance. Preventive measures were
      instituted early. But the outbreak was controlled only after intervention from
      higher administrative authorities. Lessons learnt included correct and timely
      perception of threat is essential; behavioural change of individuals is desired;
      availability of adequate health functionaries is mandatory; and complete dataset
      helps correct perception. CONCLUSION: Future strategy for control of dengue
      outbreak should include repeated and timely survey of entire area for correct
      risk perception, assessment of behavioural change among individuals; operational
      research to assess the impact of ongoing public health campaign.

PMID- 25609857
TI  - Heterogeneous vancomycin-intermediate among methicillin resistant Staphylococcus
      aureus.
AB  - BACKGROUND: Hetero-resistance vancomycin intermediate Staphylococcus aureus
      (hVISA) is phenotype, which on in-vitro susceptibility test is vancomycin
      susceptible (VSSA) but has a minority population of vancomycin intermediate
      (VISA). hVISA is responsible for vancomycin treatment failure. Population
      Analysis Profile- Area under Curve (PAP-AUC) is a test for detection of hVISA;
      however, this test is unsuitable for clinical microbiology laboratory. Tests,
      such as Brain Heart Infusion Agar with 6 MUg/ml vancomycin (BHIA6V), E test and
      Macromethod E Test (MET) are available; however reported to have variable
      results. METHODS: 58 clinical isolates of Methicillin resistant S aureus (MRSA)
      having MIC of vancomycin more than 1 MUg/ml by E test and agar dilution were
      analyzed by PAP-AUC, BHIA6V and MET. RESULT: The prevalence of hVISA was 6.9%.
      hVISA isolates were having vancomycin E test MIC >2 MUg/ml. Sensitivity of
      BHIA6V, MET and E test with MIC >2 MUg/ml were 0.75, 0.67 and 1.0 respectively;
      however, positive predictive values (PPV) were 0.43, 0.4 and 0.27 respectively
      with PAP-AUC. PAP-AUC ratio correlated with MIC by E test and MET. CONCLUSIONS:
      There is need for screening MRSA isolates showing in-vitro vancomycin
      susceptibility <=2 MUg/ml by agar dilution method for detection of hVISA. PAP-AUC
      test is unsuitable for routine laboratory testing. BHIA6V, MET and E test can be
      used for screening, however have low PPV.

PMID- 25609858
TI  - Comparison of training in neonatal resuscitation using self inflating bag and T
      piece resuscitator.
AB  - BACKGROUND: Both the self inflating bag and the T-piece resuscitator are
      recommended for neonatal resuscitation, but many health care workers are
      unfamiliar with using the latter. A prospective, comparative, observational study
      was done to determine the ease and effectiveness of training of health care
      personnel in the two devices using infant training manikins. METHODS: 100 health
      care workers, who had no prior formal training in neonatal resuscitation, were
      divided into small groups and trained in the use of the two devices by qualified
      trainers. Assessment of cognitive skills was done by pre and post MCQs.
      Psychomotor skill was assessed post training on manikins using a 10-point
      objective score. Acceptance by users was ascertained by questionnaire.
      Assessments were also done after 24 h and 3 months. Comparison was done by Chi
      square and paired t-tests. RESULTS: Pre-training cognitive tests increased from
      3.77 (+1.58) to 6.99 (+1.28) on day of training which was significant. Post
      training assessment of psychomotor skills showed significantly higher initial
      scores for the T-piece group (7.07 + 2.57) on day of training. Reassessment after
      24 h showed significant improvement in cognitive scores (9.89 + 1.24) and
      psychomotor scores in both groups (8.86 + 1.42 for self inflating bag and 9.70 +
      0.57 for T-piece resuscitator). After 3-6 months the scores in both domains
      showed some decline which was not statistically significant. User acceptability
      was the same for both devices. CONCLUSION: It is equally easy to train health
      care workers in both devices. Both groups showed good short term recall and both
      devices were equally acceptable to the users.

PMID- 25609859
TI  - ABC-VED analysis of expendable medical stores at a tertiary care hospital.
AB  - BACKGROUND: The modern system of medicine has evolved into a complex,
      sophisticated and expensive treatment modality in terms of cost of medicines and
      consumables. In any hospital, approximately 33% of total annual budget is spent
      on buying materials and supplies including medicines. ABC (Always, Better
      Control)-VED (Vital, Essential, Desirable) analysis of medical stores of a large
      teaching, tertiary care hospital of the Armed Forces was carried out to identify
      the categories of drugs needing focused managerial control. METHODS: Annual
      consumption and expenditure data of expendable medical stores for one year was
      extracted from the drug expense book, followed by classification on its annual
      usage value. Subsequently, the factor of criticality was applied to arrive at a
      decision matrix for understanding the need for selective managerial control.
      RESULTS: The study revealed that out of 1536 items considered for the study,
      6.77% (104), 19.27% (296) and 73.95% (1136) items were found to be A, B and C
      category items respectively. VED analysis revealed that vital items (V) accounted
      for 13.14% (201), essential items (E) for 56.37% (866) and desirable accounted
      for 30.49% items (469). ABC-VED matrix analysis of the inventory reveals that
      only 322 (21%) items out of an inventory of 1536 drugs belonging to category I
      will require maximum attention. CONCLUSION: Scientific inventory management tools
      need to be applied routinely for efficient management of medical stores, as it
      contributes to judicious use of limited resources and resultant improvement in
      patient care.

PMID- 25609860
TI  - Control of hospital acquired infections in the ICU: A service perspective.
AB  - BACKGROUND: The service setting has some unique strengths and weaknesses that
      must be kept in mind when organizing Hospital acquired infections (HAI)
      prevention interventions. METHODS: Following an initial study to gather data
      regarding HAI in the Surgical intensive care unit (ICU) we put into place various
      infection control interventions. The present study was carried out to analyse the
      effect of these interventions on the incidence of HAI in the ICU. RESULTS: The
      total admissions to the ICU were 253 patients. Eighty eight patients (34.78%)
      were admitted for more than 48 hr, 165 patients stayed for less than 48 h. The
      frequency of HAI was 7.95% (95% CI 3.54, 15). Hospital acquired pneumonia was
      observed in 2 of the 88 patients (2.27%) (95% CI 0.38, 7.30) which amounted to
      9.70 infections per 1000 ventilator days. Bloodstream infection was detected in 3
      out of 88 patients (3.4%) (95% CI 0.87, 8.99) amounting to 6.54 fresh infections
      per 1000 Central Venous Catheter days. Urinary tract infection was observed in 2
      (2.27%) (95% CI 0.38, 7.30) at 2.86 fresh infections per 1000 catheter days. As
      compared to the previous study we found that there was a decline of HAI ranging
      from 60 to 70%. CONCLUSION: Our study demonstrated that by meticulously following
      infection control protocols especially tailored to the service setting the
      incidence of HAI's can be reduced. However, the challenge is in maintaining the
      gains achieved since there is a rapid turnover of manpower in the ICU and a lack
      of a structured ICU design model.

PMID- 25609861
TI  - Outbreak control of community acquired pneumonia in a large military training
      institution.
AB  - BACKGROUND: Between 09 Jan 2011 to 25 Mar 2011 an outbreak of respiratory illness
      was reported from a Military Training institution. 52 cases of respiratory tract
      infection were admitted from this institution. All the cases were trainees
      between 18 and 21 years of age. Aggressive control measures were instituted along
      with the investigation of the outbreak to determine the nature of the disease and
      the causative organism. METHODS: The investigation of the outbreak was initiated
      on 08 Mar 2011 when a sudden rise in number of hospital admissions due to
      respiratory illness was noticed. Epidemiological information was collected from
      the cases. Routine blood investigations, sputum examination and chest radiograph
      of suspected cases were done. RESULTS: Total of 52 cases of respiratory illness
      were reported during the period of outbreak giving an attack rate of 25.8 per
      1000. Out of these 52 cases 23 (44.2%) were radiologically confirmed.
      Streptococcus pneumoniae was grown in 8 (25.85) out of 31 sputum samples. The
      outbreak was controlled by administration of 'supervised mass chemoprophylaxis'
      of all susceptible individuals in the institution with Tablet Azithromycin
      orally. Last suspected case was admitted to the military hospital on 25 Mar 2011.
      CONCLUSION: The study highlights the importance of Streptococcus pneumoniae as a
      causative organism for outbreaks of community acquired pneumonia (CAP) in large
      residential training institutions and reiterates the need for formulating a
      policy for continuous surveillance. It also highlights the importance of the
      novel method of using chemoprophylaxis for control of an ongoing outbreak of CAP.

PMID- 25609862
TI  - Life cycle costing as a decision making tool for technology acquisition in radio
      diagnosis.
AB  - BACKGROUND: Life cycle costing analysis is an emerging conceptual tool to
      validate capital investment in healthcare. METHODS: A preliminary study was done
      to analyze the long-term cost impact of acquiring a new 3 T MRI system when
      compared to technological upgradation of the existing 1.5 T MRI system with a
      view to evolve a decision matrix for correct investment planning and technology
      management. Operating costing method was utilized to estimate cost per unit MRI
      scan, costing inputs were considered for the existing 1.5 T and the proposed 3 T
      machine. Cost for each expected year in the life span of both 1.5 T and 3 T MRI
      scan options were then discounted to its Net Present Value. Net Present Value
      thus calculated for both the alternative options of 1.5 T and 3 T MRI machine was
      charted along with various intangible but critical Figures of Merit (FOM) to
      create a decision matrix for capital investment planning. RESULT: Considering all
      fixed and variable costs contributing towards assumed operation, unit cost per
      MRI procedure was found to be Rs. 4244.58 for the 1.5 T upgrade and Rs. 6059.37
      for the new 3 T MRI machine. Life Cycle Cost Analysis of the proposed 1.5 T
      upgrade and new 3 T machine showed a Net Present Value of Rs. 42,148,587.80 and
      Rs. 27,587,842.38 respectively. CONCLUSION: The utility of life cycle costing as
      a strategic decision making tool towards evaluating alternative options for
      capital investment planning in health care environment is reiterated.

PMID- 25609863
TI  - Detection of glycopeptide resistance genes in enterococci by multiplex PCR.
AB  - BACKGROUND: Vancomycin Resistant Enterococci (VRE) are a major cause of
      nosocomial infections. There are various phenotypic and genotypic methods of
      detection of glycopeptide resistance in enterococci. This study utilizes
      multiplex PCR for reliable detection of various glycopeptides resistance genes in
      VRE. METHOD: This study was conducted to detect and to assess the prevalence of
      vancomycin resistance among enterococci isolates. From October 2011 to June 2013,
      a total of 96 non-repetitive isolates of enterococci from various clinical
      samples were analyzed. VRE were identified by Kirby Bauer disc diffusion method
      with Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum
      inhibitory concentration (MIC) of all isolates for vancomycin and teicoplanin was
      determined by E-test. Multiplex PCR was carried out for all enterococci isolates
      using six sets of primers. RESULTS: Out of 96 isolates, 14 (14.6%) were found to
      be resistant to vancomycin by vancomycin E-test method (MIC >=32 MUg/ml). Out of
      these 14 isolates, 13 were also resistant to teicoplanin (MIC >=16 MUg/ml). VanA
      gene was detected in all the 14 isolates by Multiplex PCR. One of the PCR
      amplicons was sent for sequencing and the sequence received was submitted in the
      GenBank (GenBank accession no. KF181100). CONCLUSION: Prevalence of VRE in this
      study was 14.6%. Multiplex PCR is a robust, sensitive and specific technique,
      which can be used for rapid detection of various glycopeptide resistance genes.
      Rapid identification of patients infected or colonized with VRE is essential for
      implementation of appropriate control measures to prevent their spread.

PMID- 25609864
TI  - Prevalence and determinants of self-reported chronic bronchitis among women in
      rural Central India.
AB  - BACKGROUND: Chronic respiratory conditions are increasingly becoming a cause of
      health concern with India attributing 11% of its mortality due to non
      communicable diseases to chronic respiratory conditions. Chronic bronchitis and
      asthma take a large toll in terms of morbidity. Lesser number of studies have
      mentioned their counts of these conditions affecting women in rural area and
      therefore the present study was conducted with the objectives of determining the
      prevalence and correlates of chronic obstructive pulmonary diseases (COPD) in an
      area of a primary health centre in rural central India. METHODS: A cross
      sectional study was conducted in 24 villages of the study area. Women aged 40
      years or more were interviewed using the IUATLD questionnaire. Chronic bronchitis
      was measured by using the standard criteria for chronic bronchitis, that is,
      "Presence of cough with expectoration for more than 3 months in a year for the
      past two or more years". RESULTS: Prevalence of chronic bronchitis among women
      was found to be 2.7%. Factors like older age, presence of a cattle shed within
      house premises, storage of fertilizers inside house, history of allergy, past
      history of pulmonary tuberculosis emerged as significant correlates of chronic
      bronchitis. CONCLUSIONS: The present study provides an insight into the
      prevalence of chronic bronchitis among rural women exposed to several
      epidemiological determinants and an opportunity to address the modifiable risk
      factors.

PMID- 25609865
TI  - Comparative evaluation of surgical modalities for coverage of gingival recession:
      An Armed Forces Medical College perspective.
AB  - BACKGROUND: Esthetics represents an inseparable part of today's oral therapy, and
      several procedures have been proposed to preserve or enhance it. Gingival
      recessions may cause hypersensitivity, impaired esthetics and root caries.
      Keeping in mind patient's desire for improved esthetics and other related
      problems, every effort should be made to achieve complete root coverage. METHODS:
      Different types of modalities have been introduced to treat gingival recession
      including displaced flaps, free gingival graft, connective tissue graft,
      different type of barrier membranes and combination of different techniques. The
      aim of this study was to compare the commonly used techniques for gingival
      recession coverage and evaluate the results obtained. 73 subjects were selected
      for the present study who were randomly divided into four groups and were
      followed at baseline and 180 days where following parameters were recorded: (a)
      Assessment of gingival recession depth (RD); (b) Assessment of pocket depth (PD);
      (c) Assessment of clinical attachment level (CAL) and (d) Assessment of width of
      attached gingiva (WAG). RESULTS: Results of this study showed statistically
      significant reduction of gingival recession, with concomitant attachment gain,
      following treatment with all tested surgical techniques. However, SCTG with CAF
      technique showed the highest percentage gain in coverage of recession depth as
      well as gain in keratinized gingiva. Similar results were obtained with CAF
      alone. The use of GTR and other techniques showed less predictable coverage and
      gain in keratinized gingiva. CONCLUSION: Connective tissue grafts were
      statistically significantly superior to guided tissue regeneration for
      improvement in gingival recession reduction.

PMID- 25609866
TI  - Management of hypereosinophilia in tropical settings.
AB  - Hypereosinophilia includes a group of commonly encountered clinical situations
      with symptoms ranging from mild and clinically innocuous to devastating
      presentations with high morbidity and mortality. The presentations and
      complications can be easily missed if the clinician is unaware of the diverse
      entities responsible for hypereosinophilia. The hypereosinophilic syndromes
      encompass entities that are associated with varying degrees of organ dysfunction
      either directly due to eosinophilic infiltration or as a result of substances
      secreted by the eosinophils. These conditions may be neoplastic or reactive in
      aetiology and a diligent search for secondary causes is essential. Evaluation and
      management algorithms in the tropical setting and in developing countries may
      differ from elsewhere. A review of hypereosinophilia and hypereosinophilic
      syndromes is presented with a diagnostic and therapeutic decision making
      algorithm modified for use in the tropical setting. 

PMID- 25609867
TI  - Discovery of fifth serotype of dengue virus (DENV-5): A new public health dilemma
      in dengue control.
AB  - Dengue fever is a re-emerging public health problem with two-fifths of the world
      population being at risk of infection. Till now, dengue fever was believed to be
      caused by four different serotypes. The fifth variant DENV-5 has been isolated in
      October 2013. This serotype follows the sylvatic cycle unlike the other four
      serotypes which follow the human cycle. The likely cause of emergence of the new
      serotype could be genetic recombination, natural selection and genetic
      bottlenecks. There is no indication of the presence of DENV-5 in India. Recent
      clinical trials with the promising Chimerivax tetravalent vaccine suffered a
      setback. Discovery of DENV-5 and more such sylvatic strains in future may further
      impede the Dengue Vaccine Initiative. Integrated Vector Management holds the key
      to sustainable dengue control. Further epidemiological and ecological studies are
      needed to detect additional sylvatic dengue strains. 

PMID- 25609868
TI  - Denosumab: A bone antiresorptive drug.
AB  - Bone remodeling is the continuous process by which old bone is removed by bone
      resorbing cells, the osteoclasts and replaced by new bone synthesized by bone
      forming cells, the osteoblasts. Osteoporosis is characterized by a progressive
      loss of bone mass and microarchitecture, which leads to increased fracture risk.
      Denosumab, a human monoclonal antibody resembling natural IgG2 immunoglobulin,
      has antiresorptive activity and is distinguished from other antiresorptive drugs.
      It mimics osteoprotegerin (OPG) that binds to RANKL and hence does not allow
      RANKL to bind with RANK receptor, thereby inhibiting osteoclast differentiation,
      activation and survival exerting primarily antiresorptive action. Denosumab
      trials have shown its efficacy in postmenopausal women with osteoporosis,
      unresectable giant cell tumor of bone and significant effect in non-metastatic
      prostate cancer and delay in the time-to-first skeletal related events (SRE) and
      subsequent SRE with denosumab than zoledronic acid in patients. It is available
      as 60 mg/ml in pre-filled syringes and approved for osteoporosis in
      postmenopausal women (60 mg s.c. twice yearly), unresectable giant cell tumor of
      bone in adults and skeletally mature adolescents (120 mh s.c. monthly),
      prevention of skeletal-related events and to increase bone mass in patients at
      high risk for fracture including androgen deprivation therapy for non-metastatic
      prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer.
      Denosumab offers advantages of twice yearly dosing in osteoporosis and monthly
      dosing in giant cell tumor of bone with its novel mechanism of action and better
      tolerability. 

PMID- 25609869
TI  - Dengue in the deserts: Search and Destroy Operations.
AB  - Dengue, a viral disease transmitted by the Aedes mosquito has the potential to
      cause outbreaks in urban settings. Planned and coordinated actions including
      entomological surveillance need to be undertaken at the community level, through
      synergized efforts by all partners and stakeholders. The experience of conducting
      such a Task Force based action plan for prevention and control of dengue, in a
      desert township is highlighted in this study. 

PMID- 25609870
TI  - Laparoscopic mesh repair of Morgagni hernia in an octogenarian patient.

PMID- 25609871
TI  - Neonatal hepatic abscess with resolving portal vein thrombosis.

PMID- 25609872
TI  - Corneal ulcer? Think beyond only a bacterial etiology.

PMID- 25609873
TI  - Topiramate induced bilateral anterior uveitis with choroidal detachment and angle
      closure glaucoma.

PMID- 25609874
TI  - Calotropis induced ocular toxicity.

PMID- 25609875
TI  - Use of red contact lens in dyschromatopsia.

PMID- 25609877
TI  - Reply.

PMID- 25609876
TI  - Letter to editor.

PMID- 25609878
TI  - Letter to editor.

PMID- 25609879
TI  - Reply.

PMID- 25609881
TI  - Reply.

PMID- 25609880
TI  - Letter to editor.

PMID- 25609882
TI  - Reply.

PMID- 25609883
TI  - Letter to editor.

PMID- 25609884
TI  - Letter to editor.

PMID- 25609885
TI  - Reply.

PMID- 25609886
TI  - Acute effects of movement velocity on blood lactate and growth hormone responses
      after eccentric bench press exercise in resistance-trained men.
AB  - This study aimed to compare the effects of different velocities of eccentric
      muscle actions on acute blood lactate and serum growth hormone (GH)
      concentrations following free weight bench press exercises performed by
      resistance-trained men. Sixteen healthy men were divided into two groups: slow
      eccentric velocity (SEV; n = 8) and fast eccentric velocity (FEV; n = 8). Both
      groups performed four sets of eight eccentric repetitions at an intensity of 70%
      of their one repetition maximum eccentric (1RMecc) test, with 2-minute rest
      intervals between sets. The eccentric velocity was controlled to 3 seconds per
      range of motion for SEV and 0.5 seconds for the FEV group. There was a
      significant difference (P < 0.001) in the kinetics of blood lactate removal (at
      3, 6, 9, 15, and 20 min) and higher mean values for peak blood lactate (P =
      0.001) for the SEV group (9.1 +/- 0.5 mM) compared to the FEV group (6.1 +/- 0.4
      mM). Additionally, serum GH concentrations were significantly higher (P < 0.001)
      at 15 minutes after bench press exercise in the SEV group (1.7 +/- 0.6 ng . mL(
      1)) relative to the FEV group (0.1 +/- 0.0 ng . mL(-1)). In conclusion, the
      velocity of eccentric muscle action influences acute responses following bench
      press exercises performed by resistance-trained men using a slow velocity
      resulting in a greater metabolic stress and hormone response. 

PMID- 25609887
TI  - Cue usage in volleyball: a time course comparison of elite, intermediate and
      novice female players.
AB  - This study compared visual search strategies in adult female volleyball players
      of three levels. Video clips of the attack of the opponent team were presented on
      a large screen and participants reacted to the final pass before the spike.
      Reaction time, response accuracy and eye movement patterns were measured. Elite
      players had the highest response accuracy (97.50 +/- 3.5%) compared to the
      intermediate (91.50 +/- 4.7%) and novice players (83.50 +/- 17.6%; p<0.05).
      Novices had a remarkably high range of reaction time but no significant
      differences were found in comparison to the reaction time of elite and
      intermediate players. In general, the three groups showed similar gaze behaviour
      with the apparent use of visual pivots at moments of reception and final pass.
      This confirms the holistic model of image perception for volleyball and suggests
      that expert players extract more information from parafoveal regions. 

PMID- 25609888
TI  - Changes in physiological tremor resulting from sleep deprivation under conditions
      of increasing fatigue during prolonged military training.
AB  - The aim of the study was to define the changes of the characteristics of
      physiological postural tremor under conditions of increasing fatigue and lack of
      sleep during prolonged military training (survival). The subjects of the study
      were 15 students of the Polish Air Force Academy in Deblin. The average age was
      19.9+/-1.3 years. During the 36-hour-long continuous military training (survival)
      the subjects were deprived of sleep. Four tremor measurements were carried out
      for each of the subjects: Day 1 - morning, after rest (measurement 0); Day 2 -
      morning, after overnight physical exercise (measurement 1); afternoon, after
      continuous sleep deprivation (measurement 2); Day 3 - morning, after a full night
      sleep (measurement 3). The accelerometric method using an acceleration measuring
      kit was applied to analyse tremor. A significant difference between mean values
      of the index evaluating tremor power in low frequencies L2-4 in measurement 0 and
      measurement 3 was observed (p<0.01). No significant differences were found in
      mean values of index L10-20. Mean frequencies F2-4 differed significantly from
      each other (F2,42=4.53; p<0.01). Their values were 2.94+/-0.11, 2.99+/-0.9,
      2.93+/-0.07 and 2.91+/-0.07 for successive measurements. A gradual, significant
      decrease of F8-14 was observed (F2,42=5.143; p<0.01). Prolonged sleep deprivation
      combined with performing tasks demanding constant physical effort causes long
      lasting (over 24 hours) changes of the amplitude of low-frequency tremor changes.
      This phenomenon may significantly influence psychomotor performance,
      deteriorating the ability to perform tasks requiring movement precision. 

PMID- 25609889
TI  - Swimming exercise stimulates neuro-genesis in the subventricular zone via
      increase in synapsin I and nerve growth factor levels.
AB  - In this study, we investigated the effects of 8-weeks of swimming exercise on
      neurogenesis in the subventricular zone (SVZ) and on the levels of nerve growth
      factor (NGF) and synapsin I protein in the olfactory bulb (OB) of adult rats at a
      series of relevant time points (2 days, 1 week, 2 weeks, 4 weeks, 3 months, and 6
      months). Ninety-six male Sprague Dawley rats were divided into 2 groups: (1) a
      control group (COG; n = 48, n = 8 for each time point) and (2) a swimming
      exercise group (SEG; total n = 48; n = 8 for each time point). SEG performed
      swimming exercise for 5 days per week over a period of 8 weeks. We found that the
      number of 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU)- and doublecortin (DCX)
      positive cells was significantly higher in SEG than in COG at all time points
      (Day 2, Week 1, Week 2, Week 4, Month 3, and Month 6; p < 0.001). Furthermore,
      NGF and synapsin I protein levels were significantly higher in SEG on Day 2, and
      Weeks 1, 2, and 4 than in COG (p < 0.05 for each time point). Our findings
      suggest that regular swimming exercise in adult rats increases neurogenesis,
      neuronal survival, and neuronal maintenance in the SVZ; furthermore, swimming
      exercise increases the levels of NGF and synapsin I in the OB. 

PMID- 25609890
TI  - Anthropometric determinants of rowing ergometer performance in physically
      inactive collegiate females.
AB  - The aim of the study was to evaluate anthropometric characteristics as
      determinants of 500 m rowing ergometer performance in physically inactive
      collegiate females. In this cross-sectional study, which included 196 collegiate
      females aged 19-23 years not participating in regular physical activities, body
      mass (BM), body height (BH), length of upper limbs (LA), length of lower limbs
      (LL), body mass index (BMI), slenderness index (SI), and the Choszcz-Podstawski
      index (CPI) were measured and a stepwise multiple regression analysis was
      performed. Participants performed 500 m maximal effort on a Concept II rowing
      ergometer. BM, BH, LA, LL, and the BMI, SI and CPI indices were found to be
      statistically significant determinants of 500 m performance. The best results (T)
      were achieved by females whose BH ranged from 170 to 180 cm, with LA and LL
      ranging from 75 to 80 cm and 85 to 90 cm, respectively. The best fitting
      statistical model was identified as: T = 11.6793 LR - 0.1130 LR (2) - 0.0589 LN
      (2) + 29.2157 CPI(2) + 0.1370 LR.LN - 2.6926 LR.CPI - 211.7796. This study
      supports a need for additional studies focusing on understanding the importance
      of anthropometric differences in rowing ergometer performance, which could lead
      to establishing a better quality reference for evaluation of cardiorespiratory
      fitness tested using a rowing ergometer in collegiate females. 

PMID- 25609891
TI  - Body structure and composition of canoeists and kayakers: analysis of junior and
      teenage polish national canoeing team.
AB  - The somatic build, biological age, general state of health, mental predisposition
      and physical fitness are the criteria for selection of individuals in competitive
      sport. The present study aims to analys the differences in body structure and
      composition of canoeists and kayakers and derive conclusions regarding the
      criteria for selection of individuals incompetitive sport. The research was
      conducted on a group of 32 men aged between 17 and 22: 16 kayakers and 16
      Canadian canoeists of the junior and teenage Polish national canoeing team. Body
      composition was examined by means of bioelectrical segmental impedance. Body
      build type was determined using the anthropometric Heath-Carter method.
      Statistical analysis was performed using the Welch t-test. The examination of
      morphological features reveals significant differences in the studied parameters
      between the canoeists and kayakers. There are also significant differences
      between competitors of the Sydney 2000 Olympic Games and the studied group. We
      found that competitive kayakers should be taller than canoeists. The lower part
      of the body in kayakers is more developed than in canoeists and canoeists are
      more dehydrated than kayakers. 

PMID- 25609893
TI  - Herbal medicines for inflammatory diseases.

PMID- 25609892
TI  - The influence of Ouabain on human dendritic cells maturation.
AB  - Although known as a Na,K-ATPase inhibitor, several other cellular and systemic
      actions have been ascribed to the steroid Ouabain (Oua). Particularly in the
      immune system, our group showed that Ouabain acts on decreasing lymphocyte
      proliferation, synergizing with glucocorticoids in spontaneous thymocyte
      apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on
      human monocytes. However, Ouabain effects on dendritic cells (DCs) were not
      explored so far. Considering the peculiar plasticity and the importance of DCs in
      immune responses, the aim of our study was to investigate DC maturation under
      Ouabain influence. To generate immature DCs, human monocytes were cultured with
      IL-4 and GM-CSF (5 days). To investigate Ouabain role on DC activation, DCs were
      stimulated with TNF-alpha for 48 h in the presence or absence of Ouabain. TNF
      induced CD83 expression and IL-12 production were abolished in DCs incubated with
      100 nM Ouabain, though DC functional capacity concerning lymphocyte activation
      remained unaltered. Nevertheless, TNF-alpha-induced antigen capture
      downregulation, another maturation marker, occurred even in the presence of
      Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80
      expression was maintained. Collectively, our results suggest that DCs respond to
      Ouabain maturating into a distinct category, possibly contributing to the balance
      between immunity and tolerance.

PMID- 25609894
TI  - Infections of cardiac implantable electronic devices.

PMID- 25609895
TI  - Freezing at the his bundle.

PMID- 25609896
TI  - Cryoablation of anteroseptal accessory pathways with a his bundle electrogram on
      the ablation catheter.
AB  - BACKGROUND: Radiofrequency catheter ablations of anteroseptal (AS) accessory
      pathways (AP) in pediatric patients have higher incidence of atrioventricular
      (AV) block than other AP locations. We report our experience using cryoablation
      in pediatric patients where a His bundle electrogram was noted on the ablation
      catheter at the site of the successful ablation. METHODS AND RESULTS: We
      retrospectively reviewed all patients <=21 years that underwent cryoablation for
      an AS AP from 2005 to 2012 at our institution (n=70). Patients with a His bundle
      electrogram noted on the cryoablation catheter at the location of the successful
      lesion were identified (n=6, 8.5%). All six patients had ventricular
      preexcitation. Median age of 15.9 years (7.2 - 18.2). AV nodal function was
      monitored during the cryoablation with intermittent rapid atrial pacing conducted
      through the AV node (n=2), with atrial extra-stimulus testing (n=2), or during
      orthodromic reentrant tachycardia (n=2). Acute success occurred in all patients.
      Two patients had early recurrence of AP conduction. Both patients underwent a
      second successful cryoablation, again with a His bundle electrogram on the
      cryoablation catheter. At a median follow-up of 13 months (3 to 37 months) there
      was no recurrence of accessory pathway conduction and AVN function was normal.
      CONCLUSION: In a small number of pediatric patients with AS AP with a His bundle
      electrogram seen on the ablation catheter, the use of cryotherapy was safe and
      effective for elimination of AP conduction without impairment of AV nodal
      conduction.

PMID- 25609897
TI  - Shoulder joint dislocation as an unusual complication of defibrillation threshold
      testing following subcutaneous implantable cardioverter-defibrillator
      implantation.
AB  - A 53-year-old man underwent implantation of a totally subcutaneous ICD (S-ICD;
      Boston Scientific). He was positioned supine, with the left arm abducted,
      externally rotated (i.e. palm up) and strapped to the arm extender. The generator
      was placed in the left mid-axillary line along the 5th-6th intercostal spaces and
      the defibrillation coil was tunneled anterior to the sternum. Defibrillation
      threshold (DFT) testing with 65 Jcaused a forceful pectoralis twitch. The patient
      woke up with a painful anteriorly dislocated left shoulder. Glenohumeral
      dislocation due to DFT testing has not been previously reported. It is likely
      that this complication is specific to the S-ICD implantation, and is related to
      positioning with the arm abducted, externally rotated, and immobilized, and use
      of greater defibrillation energy with current pathway through the bulk of the
      pectoralis muscle.Precautions may include extending the arm palm down, strapping
      the arm loosely, and adduction of the arm for DFT testing. 

PMID- 25609898
TI  - Sustained ventricular tachycardia in an apparently healthy heart: a very
      localized left dominant arrhythmogenic cardiomyopathy.
AB  - A 62-year-old man admitted for presyncope presented two symptomatic sustained
      ventricular tachycardia with right bundle branch morphology and inferior axis
      suggesting a pathology of the left ventricular lateral wall, the site where
      Cardiac Magnetic Resonance demonstrated a thinned, hypokinetic segment with fibro
      fatty subepicardial infiltration. A very localized Left Dominant Arrhythmogenic
      Cardiomyopathy was diagnosed and an ICD implanted. 

PMID- 25609899
TI  - Successful Ablation of Cavotricuspid Isthmus-dependent Atrial Flutter Guided by
      Contact Force Vector in a Patient After a Tricuspid Valve Replacement.
AB  - A 46-year-old man after a tricuspid valve replacement due to traumatic severe
      tricuspid regurgitation developed cavotricuspid isthmus-dependent
      counterclockwise atrial flutter. During a linear ablation using a contact force
      sensing irrigated ablation catheter, the flutter could be terminated by a
      radiofrequency application within a deep pouch just below the bioprosthetic
      tricuspid valve. 

PMID- 25609900
TI  - Fragmented QRS and Chagas' disease.

PMID- 25609901
TI  - Response to letter to the editor regarding article "repolarization parameters are
      associated with mortality in chagas disease patients in the United States".

PMID- 25609902
TI  - Strategies for overcoming T-wave oversensing.

PMID- 25609903
TI  - Authors reply to 'strategies for overcoming T-wave oversensing'.

PMID- 25609904
TI  - Update on ventricular tachyarrhythmias and related sudden cardiac death.

PMID- 25609906
TI  - Prospective, noncomparative, nonrandomized case study of short-term outcomes of
      360 degrees  suture trabeculotomy ab interno in patients with open-angle
      glaucoma.
AB  - BACKGROUND: In this paper, we describe 360 degrees  suture trabeculotomy (360
      degrees LOT) ab interno and the short-term course in patients who underwent this
      procedure. METHODS: We prospectively studied 12 patients (12 eyes) with open
      angle glaucoma who underwent 360 degrees LOT ab interno at the Sato Eye Clinic
      between February and July 2014. The surgical procedure involved making a 1.7 mm
      temporal corneal incision, exposing an approximately 15 degrees  opening in the
      inner wall of Schlemm's canal (nasal side) using a Trabectome with a gonioscope,
      and inserting a 5-0 nylon suture rounded at the tip into Schlemm's canal opened
      via the anterior chamber. The suture was then threaded around Schlemm's canal,
      and the tip of the suture that emerged on the other side was then advanced
      through the opening to make a circumferential incision. Intraocular pressure
      (IOP), number of anti-glaucoma medications used, complications, and the surgery
      completion rate were prospectively studied. RESULTS: Mean IOP, which was 19.4
      mmHg at baseline, showed a significant decrease at each of the monthly
      observation points, reaching 13.8 mmHg at 6 months after surgery (P=0.0004,
      paired t-test). The mean number of anti-glaucoma medications decreased from 3.2
      at baseline to 1.1 at 6 months after surgery. IOP spikes >=30 mmHg were seen in
      25% of patients, but there were no other serious complications and the surgery
      completion rate was 92%. CONCLUSION: The 360 degrees LOT ab interno procedure
      preserves the conjunctiva and sclera, and has a high surgery completion rate when
      using the anterior chamber approach, and could therefore be an effective short
      term treatment of open-angle glaucoma.

PMID- 25609905
TI  - Sexually transmitted disease partner notification among African-American,
      adolescent women.
AB  - OBJECTIVE: To better understand preferences and practices regarding partner
      notification of sexually transmitted infection (STI) among female, African
      American adolescents. METHODS: Participants completed a questionnaire and STI
      testing at baseline. Those diagnosed with Chlamydia or gonorrhea were recruited
      for a follow-up study, involving another questionnaire and repeat STI testing
      after three months. RESULTS: At baseline, most participants (85.1%) preferred to
      tell their partner about an STI diagnosis themselves instead of having a health
      care provider inform him, and 71.0% preferred to bring their partner for clinic
      treatment instead of giving him pills or a prescription. Two-thirds of
      participants were classified as having high self-efficacy for partner
      notification of a positive STI diagnosis. In the multivariable analysis, older
      participants and those with fewer lifetime sexual partners were more likely to
      have high self-efficacy. Ninety-three participants (26.6%) had Chlamydia or
      gonorrhea and, of this subset, 55 participated in the follow-up study. Most
      adolescents in the follow-up study (76.4%) notified their partner about their
      infection. CONCLUSION: Although participants were willing to use most methods of
      partner notification, most preferred to tell partners themselves and few
      preferred expedited partner therapy. Traditional methods for partner notification
      and treatment may not be adequate for all adolescents in this population.

PMID- 25609907
TI  - Progression to macula-off tractional retinal detachment after a contralateral
      intraoperative intravitreal bevacizumab injection for proliferative diabetic
      retinopathy.
AB  - We report a patient with progression to a macula-off tractional retinal
      detachment in a fellow eye after a contralateral intraoperative intravitreal
      bevacizumab injection. A 32-year-old diabetic man noted decreased vision in his
      left eye 1 week following 25 gauge pars plana vitrectomy, gas tamponade, and
      intraoperative injection of bevacizumab in his right eye. Left eye visual acuity
      decreased from 20/80 to 20/200, and macula-off tractional retinal detachment was
      seen on clinical exam and imaging. Progression of tractional retinal detachment
      associated with proliferative diabetic retinopathy in a fellow eye after a
      contralateral intraoperative intravitreal bevacizumab injection may occur. 

PMID- 25609908
TI  - Posterior microphthalmos and papillomacular fold-associated cystic changes
      misdiagnosed as cystoid macular edema following cataract extraction.
AB  - PURPOSE: Novel spectral-domain optical coherence tomography (SD-OCT) findings in
      posterior microphthalmos (PM) include cystoid changes in the papillomacular fold
      (PMF). These changes may be misdiagnosed as cystoid macular edema (CME) and may
      trigger unnecessary treatment including intravitreal injections. We report a case
      that underscores this scenario aiming to increase awareness of this entity among
      ophthalmologists. METHOD: A case report. RESULTS: A 25-year-old male presented
      with a history of clear lens extraction in both eyes as a refractive procedure.
      Postoperatively, he was diagnosed with CME and received five intravitreal
      bevacizumab injections in each eye as well as oral diamox for persistent cystic
      spaces noted on OCT. He was referred to our institution with the diagnosis of non
      responding CME. A complete ophthalmic evaluation, including ultrasonography and
      SD-OCT, confirmed the diagnosis of PM and PMF with cystic cavities in the PMF. A
      fluorescein angiogram disclosed absence of macular leakage or optic nerve head
      staining indicating that the cystic cavities seen on SD-OCT are not due to
      postoperative CME but are rather the intrinsic cystic changes commonly seen in
      eyes with PM and a PMF. These cystic cavities were incorrectly thought to
      represent postoperative CME, which triggered the unnecessary treatment and lack
      of response. CONCLUSION: Cystic-like cavities are a component of the PMF in PM
      eyes and may be misdiagnosed as CME, especially in a postoperative setting. This
      case underscores the importance of understanding the intrinsic features of the
      PMF in eyes with PM and may help increase awareness among ophthalmologists of
      such a potentially confusing scenario.

PMID- 25609910
TI  - The use of endoillumination probe-assisted Descemet membrane endothelial
      keratoplasty for bullous keratopathy secondary to argon laser iridotomy.
AB  - PURPOSE: To report the first case of Descemet membrane endothelial keratoplasty
      (DMEK) for bullous keratopathy (BK) secondary to argon laser iridotomy (ALI).
      PATIENT: A 71-year-old woman presented with decreased visual acuity in her right
      eye due to BK secondary to ALI that was performed 10 years prior. RESULTS:
      Phacosurgery was performed first, followed by successful DMEK 4 months later. A
      DMEK shooter was used for donor insertion, which allowed for a stable anterior
      chamber during donor insertion, even when the anterior chamber was quite shallow.
      Also, removal of edematous epithelial cells and endoillumination probe-assisted
      DMEK was quite useful to visualize DMEK graft on the background of the dark brown
      iris seen in Asian eyes. The patient's best corrected visual acuity rapidly
      increased from 20/200 to 25/20 after 1 month, with complete resolution of corneal
      edema. CONCLUSION: We reported the first successful DMEK case for BK secondary to
      ALI. The use of a DMEK shooter for donor insertion and endoillumination
      assistance to visualize the DMEK graft was a useful technique for BK secondary to
      ALI.

PMID- 25609909
TI  - Pediatric cataract: challenges and future directions.
AB  - Cataract is a significant cause of visual disability in the pediatric population
      worldwide and can significantly impact the neurobiological development of a
      child. Early diagnosis and prompt surgical intervention is critical to prevent
      irreversible amblyopia. Thorough ocular evaluation, including the onset,
      duration, and morphology of a cataract, is essential to determine the timing for
      surgical intervention. Detailed assessment of the general health of the child,
      preferably in conjunction with a pediatrician, is helpful to rule out any
      associated systemic condition. Although pediatric cataracts have a diverse
      etiology, with the majority being idiopathic, genetic counseling and molecular
      testing should be undertaken with the help of a genetic counselor and/or
      geneticist in cases of hereditary cataracts. Advancement in surgical techniques
      and methods of optical rehabilitation has substantially improved the functional
      and anatomic outcomes of pediatric cataract surgeries in recent years. However,
      the phenomenon of refractive growth and the process of emmetropization have
      continued to puzzle pediatric ophthalmologists and highlight the need for future
      prospective studies. Posterior capsule opacification and secondary glaucoma are
      still the major postoperative complications necessitating long-term surveillance
      in children undergoing cataract surgery early in life. Successful management of
      pediatric cataracts depends on individualized care and experienced teamwork. We
      reviewed the etiology, preoperative evaluation including biometry, choice of
      intraocular lens, surgical techniques, and recent developments in the field of
      childhood cataract. 

PMID- 25609912
TI  - Reversal of a presbyopic LASIK treatment.
AB  - We report on a 72 year-old pseudophakic patient who had been implanted with a
      monofocal intraocular lens, and who underwent a unilateral Supracor laser
      assisted in-situ keratomileusis (LASIK) procedure to correct presbyopia and
      hyperopia. Uncorrected near visual acuity was improved, but the patient
      complained of glare, halo, reduced distance vision, and poor night driving vision
      due to treatment decentration. One year following the surgery, a reversal
      procedure was conducted with a wavefront-guided aspheric treatment to reverse the
      presbyopic correction while still maintaining the hyperopic correction. This
      resulted in 20/25 uncorrected distance visual acuity, and it eliminated the
      dysphotopsia symptoms. We believe that this is the first reported case
      demonstrating the ability to reverse the Supracor LASIK presbyopic procedure
      using wavefront-guided treatment in a case of an unsatisfactory outcome. 

PMID- 25609913
TI  - Implantable inlay devices for presbyopia: the evidence to date.
AB  - By 2020, it is estimated that 2.1 billion people will be presbyopic, and the
      demand for spectacle independence in this group is growing. This review article
      provides an overview of the three commercially available corneal inlays for the
      correction of presbyopia. Safety, efficacy, visual outcomes, and complications
      are analyzed for all three inlays according to published peer-reviewed data. 

PMID- 25609914
TI  - Use of infant donor tissue in endothelial keratoplasty.

PMID- 25609911
TI  - Endophthalmitis: state of the art.
AB  - Endophthalmitis is an uncommon diagnosis but can have devastating visual
      outcomes. Endophthalmitis may be endogenous or exogenous. Exogenous
      endophthalmitis is caused by introduction of pathogens through mechanisms such as
      ocular surgery, open-globe trauma, and intravitreal injections. Endogenous
      endophthalmitis occurs as a result of hematogenous spread of bacteria or fungi
      into the eye. These categories of endophthalmitis have different risk factors and
      causative pathogens, and thus require different diagnostic, prevention, and
      treatment strategies. Novel diagnostic techniques such as real-time polymerase
      chain reaction (RT-PCR) have been reported to provide improved diagnostic results
      over traditional culture techniques and may have a more expanded role in the
      future. While the role of povidone-iodine in prophylaxis of postoperative
      endophthalmitis is established, there remains controversy with regard to the
      effectiveness of other measures, including prophylactic antibiotics. The
      Endophthalmitis Vitrectomy Study (EVS) has provided us with valuable treatment
      guidelines. However, these guidelines cannot be directly applied to all
      categories of endophthalmitis, highlighting the need for continued research into
      attaining improved treatment outcomes. 

PMID- 25609915
TI  - Vipegitide: a folded peptidomimetic partial antagonist of alpha2beta1 integrin
      with antiplatelet aggregation activity.
AB  - Linear peptides containing the sequence WKTSRTSHY were used as lead compounds to
      synthesize a novel peptidomimetic antagonist of alpha2beta1 integrin, with
      platelet aggregation-inhibiting activity, named Vipegitide. Vipegitide is a 13
      amino acid, folded peptidomimetic molecule, containing two alpha-aminoisobutyric
      acid residues at positions 6 and 8 and not stable in human serum. Substitution of
      glycine and tryptophan residues at positions 1 and 2, respectively, with a unit
      of two polyethylene glycol (PEG) molecules yielded peptidomimetic Vipegitide
      PEG2, stable in human serum for over 3 hours. Vipegitide and Vipegitide-PEG2
      showed high potency (7*10(-10) M and 1.5*10(-10) M, respectively) and
      intermediate efficacy (40% and 35%, respectively) as well as selectivity toward
      alpha2 integrin in inhibition of adhesion of alpha1/alpha2 integrin
      overexpressing cells toward respective collagens. Interaction of both
      peptidomimetics with extracellular active domain of alpha2 integrin was confirmed
      in cell-free binding assay with recombinant alpha2 A-domain. Integrin alpha2beta1
      receptor is found on the platelet membrane and triggers collagen-induced platelet
      aggregation. Vipegitide and Vipegitide-PEG2 inhibited alpha2beta1 integrin
      mediated adhesion of human and murine platelets under the flow condition, by 50%.
      They efficiently blocked adenosine diphosphate- and collagen I-induced platelet
      aggregation in platelet rich plasma and whole human blood. Higher potency of
      Vipegitide than Vipegitide-PEG2 is consistent with results of computer modeling
      of the molecules in water. These peptidomimetic molecules were acutely tolerated
      in mice upon intravenous bolus injection of 50 mg/kg. These results underline the
      potency of Vipegitide and Vipegitide-PEG2 molecules as platelet aggregation
      inhibiting drug lead compounds in antithrombotic therapy. 

PMID- 25609916
TI  - Sample sizes in dosage investigational clinical trials: a systematic evaluation.
AB  - The main purpose of investigational phase II clinical trials is to explore
      indications and effective doses. However, as yet, there is no clear rule and no
      related published literature about the precise suitable sample sizes to be used
      in phase II clinical trials. To explore this, we searched for clinical trials in
      the ClinicalTrials.gov registry using the keywords "dose-finding" or "dose
      response" and "Phase II". The time span of the search was September 20, 1999, to
      December 31, 2013. A total of 2103 clinical trials were finally included in our
      review. Regarding sample sizes, 1,156 clinical trials had <40 participants in
      each group, accounting for 55.0% of the studies reviewed, and only 17.2% of the
      studies reviewed had >100 patient cases in a single group. Sample sizes used in
      parallel study designs tended to be larger than those of crossover designs
      (median sample size 151 and 37, respectively). In conclusion, in the earlier
      phases of drug research and development, there are a variety of designs for
      dosage investigational studies. The sample size of each trial should be
      comprehensively considered and selected according to the study design and
      purpose. 

PMID- 25609917
TI  - Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of
      iron deficiency anemia.
AB  - According to the World Health Organization, 46% of the world's children suffer
      from anemia, which is usually treated with iron supplements such as ferrous
      sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles,
      in order to find an innovative way for alleviating the disadvantages associated
      with commercially available tablets. These limitations include adverse effects on
      the digestive system resulting in constipation and blood in the stool. The second
      drawback is the high variability in the absorption of iron and thus in its
      bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot
      homogenization/ultrasonication. Solubility of ferrous sulfate in different solid
      lipids was measured, and effects of process variables such as the surfactant type
      and concentration, homogenization and ultrasonication times, and charge-inducing
      agent on the particle size, zeta potential, and encapsulation efficiency were
      determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were
      studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888
      ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average
      particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic
      study revealed more than fourfold enhanced bioavailability. In conclusion, Fe
      SLNs could be a promising carrier for iron with enhanced oral bioavailability. 

PMID- 25609918
TI  - Screening strategies to identify HSP70 modulators to treat Alzheimer's disease.
AB  - Alzheimer's disease, the most common type of dementia, is a progressive brain
      disease that destroys cognitive function and eventually leads to death. In
      patients with Alzheimer's disease, beta amyloids and tau proteins form
      plaques/oligomers and oligomers/tangles that affect the ability of neurons to
      function properly. Heat shock protein 70 (HSP70) has the ability to prevent
      aggregation/oligomerization of beta amyloid/tau proteins, making it a potential
      drug target. To determine this potential, it is essential that we have
      appropriate in vitro and cell-based assays that help identify specific molecules
      that affect this aggregation or oligomerization through HSP70. Potential drug
      candidates could be identified through a series of assays, starting with ATPase
      assays, followed by aggregation assays with enzymes/proteins and cell-based
      systems. ATPase assays are effective in identification of ATPase modulators but
      do not determine the effect of the molecule on beta amyloid and tau proteins.
      Molecules identified through ATPase assays are validated by thioflavin T
      aggregation assays in the presence of HSP70. These assays help uncover if a
      molecule affects beta amyloid and tau through HSP70, but are limited by their in
      vitro nature. Potential drug candidates are further validated through cell-based
      assays using mammalian, yeast, or bacterial cultures. However, while these assays
      are able to determine the effect of a specific molecule on beta amyloid and tau,
      they fail to determine whether the action is HSP70-dependent. The creation of a
      novel, direct assay that can demonstrate the antiaggregation effect of a molecule
      as well as its action through HSP70 would reduce the number of false-positive
      drug candidates and be more cost-effective and time-effective. 

PMID- 25609919
TI  - Current and emerging treatment options for ANCA-associated vasculitis: potential
      role of belimumab and other BAFF/APRIL targeting agents.
AB  - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises
      several clinical entities with diverse clinical presentations, outcomes, and
      nonunifying pathogenesis. AAV has a clear potential for relapses, and shows
      unpredictable response to treatment. Cyclophosphamide-based therapies have
      remained the hallmark of induction therapy protocols for more than four decades.
      Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has
      proved beneficial in AAV, leading to Food and Drug Administration approval of
      rituximab in combination with corticosteroids for the treatment of AAV in adults.
      Rituximab for ANCA-associated vasculitis and other clinical trials provided clear
      evidence that rituximab was not inferior to cyclophosphamide for remission
      induction, and rituximab appeared even more beneficial in patients with relapsing
      disease. This raised hopes that other B-cell-targeted therapies directed either
      against CD19, CD20, CD22, or B-cell survival factors, B-cell activating factor of
      the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand could
      also be beneficial for the management of AAV. BAFF neutralization with the fully
      humanized monoclonal antibody belimumab has already shown success in human
      systemic lupus erythematosus and, along with another anti-BAFF reagent
      blisibimod, is currently undergoing Phase II and III clinical trials in AAV.
      Local production of BAFF in granulomatous lesions and elevated levels of serum
      BAFF in AAV provide a rationale for BAFF-targeted therapies not only in AAV but
      also in other forms of vasculitis such as Behcet's disease, large-vessel
      vasculitis, or cryoglobulinemic vasculitis secondary to chronic hepatitis C
      infection. BAFF-targeted therapies have a very solid safety profile, and may have
      an additional benefit of preferentially targeting newly arising autoreactive B
      cells over non-self-reactive B cells. 

PMID- 25609921
TI  - Letter to the editor: naltrexone sustained-release/bupropion sustained-release
      for the management of obesity: review of the data to date.

PMID- 25609920
TI  - Plumbagin elicits differential proteomic responses mainly involving cell cycle,
      apoptosis, autophagy, and epithelial-to-mesenchymal transition pathways in human
      prostate cancer PC-3 and DU145 cells.
AB  - Plumbagin (PLB) has exhibited a potent anticancer effect in preclinical studies,
      but the molecular interactome remains elusive. This study aimed to compare the
      quantitative proteomic responses to PLB treatment in human prostate cancer PC-3
      and DU145 cells using the approach of stable-isotope labeling by amino acids in
      cell culture (SILAC). The data were finally validated using Western blot assay.
      First, the bioinformatic analysis predicted that PLB could interact with 78
      proteins that were involved in cell proliferation and apoptosis, immunity, and
      signal transduction. Our quantitative proteomic study using SILAC revealed that
      there were at least 1,225 and 267 proteins interacting with PLB and there were
      341 and 107 signaling pathways and cellular functions potentially regulated by
      PLB in PC-3 and DU145 cells, respectively. These proteins and pathways played a
      critical role in the regulation of cell cycle, apoptosis, autophagy, epithelial
      to mesenchymal transition (EMT), and reactive oxygen species generation. The
      proteomic study showed substantial differences in response to PLB treatment
      between PC-3 and DU145 cells. PLB treatment significantly modulated the
      expression of critical proteins that regulate cell cycle, apoptosis, and EMT
      signaling pathways in PC-3 cells but not in DU145 cells. Consistently, our
      Western blotting analysis validated the bioinformatic and proteomic data and
      confirmed the modulating effects of PLB on important proteins that regulated cell
      cycle, apoptosis, autophagy, and EMT in PC-3 and DU145 cells. The data from the
      Western blot assay could not display significant differences between PC-3 and
      DU145 cells. These findings indicate that PLB elicits different proteomic
      responses in PC-3 and DU145 cells involving proteins and pathways that regulate
      cell cycle, apoptosis, autophagy, reactive oxygen species production, and
      antioxidation/oxidation homeostasis. This is the first systematic study with
      integrated computational, proteomic, and functional analyses revealing the
      networks of signaling pathways and differential proteomic responses to PLB
      treatment in prostate cancer cells. Quantitative proteomic analysis using SILAC
      represents an efficient and highly sensitive approach to identify the target
      networks of anticancer drugs like PLB, and the data may be used to discriminate
      the molecular and clinical subtypes, and to identify new therapeutic targets and
      biomarkers, for prostate cancer. Further studies are warranted to explore the
      potential of quantitative proteomic analysis in the identification of new targets
      and biomarkers for prostate cancer. 

PMID- 25609922
TI  - Tacrolimus in preventing transplant rejection in Chinese patients--optimizing
      use.
AB  - Tacrolimus is a product of fermentation of Streptomyces, and belongs to the
      family of calcineurin inhibitors. It is a widely used immunosuppressive drug for
      preventing solid-organ transplant rejection. Compared to cyclosporine, tacrolimus
      has greater immunosuppressive potency and a lower incidence of side effects. It
      has been accepted as first-line treatment after liver and kidney transplantation.
      Tacrolimus has specific features in Chinese transplant patients; its in vivo
      pharmacokinetics, treatment regimen, dose and administration, and adverse-effect
      profile are influenced by multiple factors, such as genetics and the spectrum of
      primary diseases in the Chinese population. We reviewed the clinical experience
      of tacrolimus use in Chinese liver- and kidney-transplant patients, including the
      pharmacology of tacrolimus, the immunosuppressive effects of tacrolimus versus
      cyclosporine, effects of different factors on tacrolimus metabolism on Chinese
      patients, personalized medicine, clinical safety profile, and patient
      satisfaction and adherence. This article provides guidance for the rational and
      efficient use of tacrolimus in Chinese organ-transplant patients. 

PMID- 25609924
TI  - HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella
      alba leaf extract as a treatment for hypercholesterolemia.
AB  - The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key
      enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA
      reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs,
      statins, are commonly used for the treatment of hypercholesterolemia. Due to the
      side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are
      needed. In this study, 25 medicinal plant methanol extracts were screened for
      anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest
      inhibitory effect at about 74%. Thus, B. alba was examined in order to
      investigate its phytochemical components. Gas chromatography with tandem mass
      spectrometry and reversed phase high-performance liquid chromatography analysis
      revealed the presence of phenol 2,6-bis(1,1-dimethylethyl), 1-heptatriacotanol,
      oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and alpha
      tocopherol, which have been reported to possess antihypercholesterolemic effects.
      Further investigation of in vivo models should be performed in order to confirm
      its potential as an alternative treatment for hypercholesterolemia and related
      cardiovascular diseases. 

PMID- 25609923
TI  - Inhibition of mitotic Aurora kinase A by alisertib induces apoptosis and
      autophagy of human gastric cancer AGS and NCI-N78 cells.
AB  - Gastric cancer is one of the most common cancers and responds poorly to current
      chemotherapy. Alisertib (ALS) is a second-generation, orally bioavailable, highly
      selective small-molecule inhibitor of the serine/threonine protein kinase Aurora
      kinase A (AURKA). ALS has been shown to have potent anticancer effects in
      preclinical and clinical studies, but its role in gastric cancer treatment is
      unclear. This study aimed to investigate the cancer cell-killing effect of ALS on
      gastric cancer cell lines AGS and NCI-N78, with a focus on cell proliferation,
      cell-cycle distribution, apoptosis, and autophagy and the mechanism of action.
      The results showed that ALS exhibited potent growth-inhibitory, proapoptotic, and
      proautophagic effects on AGS and NCI-N78 cells. ALS concentration-dependently
      inhibited cell proliferation and induced cell-cycle arrest at G2/M phase in both
      cell lines, with a downregulation of cyclin-dependent kinase 1 and cyclin B1
      expression but upregulation of p21 Waf1/Cip1, p27 Kip1, and p53 expression. ALS
      induced mitochondria-mediated apoptosis and autophagy in both AGS and NCI-N78
      cells. ALS induced the expression of proapoptotic proteins but inhibited the
      expression of antiapoptotic proteins, with a significant increase in the release
      of cytochrome c and the activation of caspase 9 and caspase 3 in both cell lines.
      ALS induced inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B
      (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein
      kinase (MAPK) signaling pathways while activating the 5'-adenosine monophosphate
      activated protein kinase (AMPK) signaling pathway as indicated by their altered
      phosphorylation, contributing to the proautophagic effects of ALS. SB202191 and
      wortmannin enhanced the autophagy-inducing effect of ALS in AGS and NCI-N78
      cells. Notably, ALS treatment significantly decreased the ratio of phosphorylated
      AURKA over AURKA, which may contribute, at least in part, to the inducing effects
      of ALS on cell-cycle arrest and autophagy in AGS and NCI-N78 cells. Taken
      together, these results indicate that ALS exerts a potent inhibitory effect on
      cell proliferation but inducing effects on cell-cycle arrest, mitochondria
      dependent apoptosis, and autophagy with the involvement of PI3K/Akt/mTOR, p38
      MAPK, and AURKA-mediated signaling pathways in AGS and NCI-N78 cells. 

PMID- 25609925
TI  - Factors associated with adherence to nucleos(t)ide analogs in chronic hepatitis B
      patients: results from a 1-year follow-up study.
AB  - Little is known about the factors associated with patient compliance with
      nucleos(t)ide analog (NUC) treatment for chronic hepatitis B (CHB). The purpose
      of this study was to examine the association between sociodemographic and
      clinical characteristics and adherence to NUCs among patients with CHB. A total
      of 211 CHB patients receiving NUC monotherapy were asked to report the number of
      prescribed doses of medication they had taken during the last 90 days. A total of
      four 3-month adherence scores were averaged to obtain a combined rate of NUC
      adherence during a 1-year follow up period. The mean age of the patients was 29.6
      years, 79% were men, and 68% had no prior NUC treatment for CHB. Females,
      patients without a previous NUC treatment, and those who had NUC drug resistance
      showed better adherence to NUC treatment, and compliance was better with
      telbivudine than with lamivudine and entecavir. 

PMID- 25609926
TI  - Use of Q methodology to assess the concerns of adult female individuals seeking
      orthodontic treatment.
AB  - BACKGROUND: Orthodontic treatment may cause functional restrictions, discomfort,
      and pain, which may lead to dental anxiety and noncooperation among patients.
      This study aimed to assess the concerns of adult female patients with respect to
      such treatment. PATIENTS AND METHODS: We conducted an explorative study using Q
      methodology among 40 adult female patients with different educational and social
      backgrounds in Wenzhou, People's Republic of China. We asked participants to rank
      a set of 41 statements about seeking orthodontic treatment on an 11-point scale
      from "agree most" to "disagree most". The collected data were analyzed using the
      PQ Method 2.35 program. We extracted significant viewpoints using centroid factor
      extraction and varimax rotation. RESULTS: We identified major factors based on
      how the patients ranked statements. Patients in group 1 worried about lack of
      information about orthodontic treatment, and may have suffered from dental
      phobia; patients in group 2 were all single women, and they were worried that the
      braces might lower their chances of finding a partner; patients in group 3
      worried about appearance and speech with braces; and patients in group 4 worried
      about cost, pain, and dental hygiene. The remaining participants who had other
      viewpoints did not load to any of these four groups. CONCLUSION: The concerns of
      adult female individuals seeking orthodontic treatment are complex. A significant
      feature of this study was using Q methodology to analyze the psychological
      characteristics of the patients. This study identified four typical
      characterizations that are associated with each group, and our findings may aid
      orthodontists in improving doctor-patient relationships.

PMID- 25609927
TI  - Words of wisdom - patient perspectives to guide recovery for older adults after
      hip fracture: a qualitative study.
AB  - Recovery after hip fracture is complex involving many transitions along the care
      continuum. The recovery process, and these transitions, often present significant
      challenges for older adults and their families and caregivers. There is an
      identified need for more targeted information to support older adults and their
      families throughout the recovery process.Therefore, our goal was to understand
      the recovery phase after hip fracture from the patient perspective, and identify
      specific messages that could be integrated into future educational material for
      clinical practice to support patients during recovery. Using a qualitative
      description design guided by a strengths-based focus, we invited men and women
      60+ years with previous hip fracture and their family members/caregivers to
      participate in interviews. We used purposive criterion sampling within the
      community setting to recruit participants. We followed a semi-structured guide to
      conduct the interviews, either in person or over the telephone, and focused
      questions on experiences with hip fracture and factors that enabled recovery. Two
      investigators coded and analyzed interview transcripts to identify key messages.
      We interviewed a total of 19 participants: eleven older adults who sustained a
      hip fracture and eight family member/caregivers. Participants described three
      main messages that enabled recovery: 1) seek support; 2) move more; and 3)
      preserve perspective. Participants provided vital information about their
      recovery experience from hip fracture. In future, this knowledge can be
      incorporated into patient-centered education and shared with older adults, their
      families, and health care professionals across the continuum of care. 

PMID- 25609928
TI  - Narrative review of telemedicine consultation in medical practice.
AB  - BACKGROUND: The use of telemedicine has grown across several medical fields, due
      to the increasing number of "e-patients". OBJECTIVE: This narrative review gives
      an overview of the growing use of telemedicine in different medical specialties,
      showing how its use can improve medical care. METHODS: A PubMed/Medline, Embase,
      Web of Science, and Scopus search was performed using the following keywords:
      telemedicine, teleconsultation, telehealth, e-health, and e-medicine. Selected
      papers from 1996 to 2014 were chosen on the basis of their content (quality and
      novelty). RESULTS: Telemedicine has already been applied to different areas of
      medical practice, and it is as effective as face-to-face medical care, at least
      for the diagnosis and treatment of some pathological conditions. CONCLUSION:
      Telemedicine is time- and cost-effective for both patients and health care
      professionals, encouraging its use on a larger scale. Telemedicine provides
      specialist medical care to patients who have poor access to hospitals, and
      ensures continuity of care and optimal use of available health resources. The use
      of telemedicine opens new perspectives for patients seeking a medical second
      opinion for their pathology, since they can have remote access to medical
      resources that would otherwise require enormous costs and time.

PMID- 25609930
TI  - Perspectives on reasons of medication nonadherence in psychiatric patients.
AB  - PURPOSE: This study was carried out to evaluate factors resulting in medication
      nonadherence within 6 months before admission to the psychiatric service of our
      hospital for bipolar disorder, schizophrenia/schizoaffective disorder,
      depression, and other psychiatric diseases. PATIENTS AND METHODS: Two hundred and
      three patients admitted to the Psychiatry Service of the Medical Faculty were
      included in this study. Sociodemographic parameters and clinical findings within
      6 months before admission and patients' views on reasons of medication
      nonadherence were examined. RESULTS: Patients were classified into four groups
      according to their diagnosis: bipolar disorder (n=68, 33.5%),
      schizophrenia/schizoaffective disorder (n=59, 29.1%), depression (n=39, 19.2%),
      and others (n=37, 18.2%). The ratio of medication nonadherence was higher in the
      bipolar disorder group when compared to the groups with
      schizophrenia/schizoaffective disorder, depression, and other disorders (12.1%,
      18.2%, and 24.2% vs 45.5%); however, the ratio of medication nonadherence was
      similar in schizophrenia/schizoaffective disorder, depression, and the others
      group. In logistic regression analysis, irregular follow-up (odds ratio [OR]:
      5.7; 95% confidence interval [CI]: 2.92-11.31) and diagnosis (OR: 1.5; 95% CI:
      1.07-1.95) were determined to be important risk factors for medication
      nonadherence. The leading factors for medication nonadherence were: "not willing
      to use medication", "not accepting the disease", and "being disturbed by side
      effects" in the bipolar disorder group, "not accepting the disease" in the
      schizophrenia/schizoaffective disorder group, "feeling well" in the depression
      group, and "being disturbed by side effects" in the other diseases group.
      CONCLUSION: Medication nonadherence is an important problem in psychiatric
      patients and should be dealt with by taking into account the diagnosis,
      attendance to follow-up appointments, and the patient's attitude. Ensuring
      regular attendance to follow-up appointments, adjusting the management plan
      according to the diagnosis, and improving their thoughts about resistance to
      medication can be beneficial in terms of medication adherence.

PMID- 25609929
TI  - Medication adherence in the management of nocturia: challenges and solutions.
AB  - OBJECTIVE: Nocturia affects millions of men and women. No prior reviews or meta
      analyses have explored the issue of adherence in nocturia patients. The objective
      of our study was to examine the attributes and their interaction that might
      impact pharmacological adherence in nocturia care using a conceptual model of
      adherence. MATERIALS AND METHODS: A literature search of the Medline, PubMed,
      Embase, PsycInfo, and CINAHL databases for studies published between January 1990
      and June 2014 was conducted. We developed a conceptual model in order to
      facilitate our review. RESULTS: Currently, multiple treatment options for
      nocturia exist, depending on the underlying cause. Adherence to nocturia
      treatment and outcomes are complex and intertwined, and nonadherence to nocturia
      treatment is common. In 15 studies meeting eligibility criteria, behavioral and
      pharmacologic interventions for nocturia were associated with reduced nocturia
      symptoms. Urinary symptoms that are associated with nocturia need individualized
      management depending on renal and hepatic function, medical comorbidities, and
      ongoing medication use in a patient. Another important factor related to
      adherence is the bother. Although nocturia is defined as nighttime-voiding
      frequency of one or more, not all persons may find this bothersome. The degree of
      bother is subjective, and may change from person to person. However, there is no
      information related to the association between bother and adherence to medication
      or behavioral treatments for nocturia. Medication dosing convenience, preference,
      and cost play important roles in adherence. We present a patient-centered
      conceptual model that brings together the various dimensions of medication
      adherence for nocturia. CONCLUSION: Few studies have explored adherence to
      medication and related factors in the care of nocturia. Our conceptual model can
      aid development of interventions to improve adherence to nocturia medications.

PMID- 25609931
TI  - Innovations in nanotechnology for water treatment.
AB  - Important challenges in the global water situation, mainly resulting from
      worldwide population growth and climate change, require novel innovative water
      technologies in order to ensure a supply of drinking water and reduce global
      water pollution. Against this background, the adaptation of highly advanced
      nanotechnology to traditional process engineering offers new opportunities in
      technological developments for advanced water and wastewater technology
      processes. Here, an overview of recent advances in nanotechnologies for water and
      wastewater treatment processes is provided, including nanobased materials, such
      as nanoadsorbents, nanometals, nanomembranes, and photocatalysts. The beneficial
      properties of these materials as well as technical barriers when compared with
      conventional processes are reported. The state of commercialization is presented
      and an outlook on further research opportunities is given for each type of
      nanobased material and process. In addition to the promising technological
      enhancements, the limitations of nanotechnology for water applications, such as
      laws and regulations as well as potential health risks, are summarized. The legal
      framework according to nanoengineered materials and processes that are used for
      water and wastewater treatment is considered for European countries and for the
      USA. 

PMID- 25609932
TI  - New-generation filler based on cross-linked carboxymethylcellulose: study of 350
      patients with 3-year follow-up.
AB  - PURPOSE: In recent years there has been a growing interest in nonsurgical
      procedures for facial rejuvenation. Hyaluronic acid is currently the most widely
      used dermal filler for the treatment of facial wrinkles. However, new products
      with interesting features are being introduced into the market. Cross-linked
      carboxymethylcellulose is one of these and represents a new alternative for the
      correction of wrinkles and facial defects. PATIENTS AND METHODS: The
      retrospective, multicenter, open-label study on nasolabial folds reported here
      was carried out between January 2010 and April 2014 on 350 subjects between 22
      and 67 years of age for a 36-month follow-up period in order to consistently and
      extensively assess the safety and performance of this treatment. RESULTS: The
      study revealed effective and durable correction of nasolabial wrinkles for
      periods of 9-12 months. Product reapplication over a 36-month period did not lead
      to an increase in adverse effects, which always remained rare and of little
      clinical significance, usually consisting of bruising and redness. CONCLUSION:
      Cross-linked carboxymethyl cellulose has been shown to be a safe and effective
      alternative to the resorbable products currently on the market.

PMID- 25609934
TI  - Dental prophylaxis decreases the risk of acute myocardial infarction: a
      nationwide population-based study in Taiwan.
AB  - PURPOSE: To investigate the association between periodontal disease (PD) and
      acute myocardial infarction (AMI), and evaluate the effect of dental prophylaxis
      on the incidence rate (IR) of AMI. METHODS: The Longitudinal Health Insurance
      Database 2000 from the National Health Insurance program was used to identify
      511,630 patients with PD and 208,713 without PD during 2000-2010. Subjects with
      PD were grouped according to treatment (dental prophylaxis, intensive treatment,
      and PD without treatment). The IRs of AMI during the 10-year follow-up period
      were compared among groups. Cox regression analysis adjusted for age, sex,
      socioeconomic status, residential urbanicity, and comorbidities was used to
      evaluate the effect of PD treatment on the incidence of AMI. RESULTS: The IR of
      AMI among subjects without PD was 0.19%/year. Among those with PD, the IR of AMI
      was lowest in the dental prophylaxis group (0.11%/year), followed by the
      intensive treatment (0.28%/year) and PD without treatment (0.31%/year; P<0.001)
      groups. Cox regression showed that the hazard ratio (HR) for AMI was
      significantly lower in the dental prophylaxis group (HR =0.90, 95% confidence
      interval =0.86-0.95) and higher in the intensive treatment (HR =1.09, 95%
      confidence interval =1.03-1.15) and PD without treatment (HR =1.23, 95%
      confidence interval =1.13-1.35) groups than in subjects without PD. CONCLUSION:
      PD is associated with a higher risk of AMI, which can be reduced by dental
      prophylaxis to maintain periodontal health.

PMID- 25609935
TI  - Comparison of strength training, aerobic training, and additional physical
      therapy as supplementary treatments for Parkinson's disease: pilot study.
AB  - INTRODUCTION: Physical rehabilitation is commonly used in patients with
      Parkinson's disease (PD) to improve their health and alleviate the symptoms.
      OBJECTIVE: We compared the effects of three programs, strength training (ST),
      aerobic training (AT), and physiotherapy, on motor symptoms, functional capacity,
      and electroencephalographic (EEG) activity in PD patients. METHODS: Twenty-two
      patients were recruited and randomized into three groups: AT (70% of maximum
      heart rate), ST (80% of one repetition maximum), and physiotherapy (in groups).
      Subjects participated in their respective interventions twice a week for 12
      weeks. The assessments included measures of disease symptoms (Unified Parkinson's
      Disease Rating Scale [UPDRS]), functional capacity (Senior Fitness Test), and EEG
      before and after 12 weeks of intervention. RESULTS: The PD motor symptoms (UPDRS
      III) in the group of patients who performed ST and AT improved by 27.5% (effect
      size [ES]=1.25, confidence interval [CI]=-0.11, 2.25) and 35% (ES=1.34, CI=-0.16,
      2.58), respectively, in contrast to the physiotherapy group, which showed a 2.9%
      improvement (ES=0.07, CI=-0.85, 0.99). Furthermore, the functional capacity of
      all three groups improved after the intervention. The mean frequency of the EEG
      analysis mainly showed the effect of the interventions on the groups (F=11.50,
      P=0.0001). CONCLUSION: ST and AT in patients with PD are associated with improved
      outcomes in disease symptoms and functional capacity.

PMID- 25609933
TI  - Optimal management of breast cancer in the elderly patient: current perspectives.
AB  - Breast cancer (BC) is the most common female malignancy in the world and almost
      one third of cases occur after 70 years of age. Optimal management of BC in the
      elderly is a real challenge and requires a multidisciplinary approach, mainly
      because the elderly population is heterogeneous. In this review, we describe the
      various possibilities of treatment for localized or metastatic BC in an aging
      population. We provide an overview of the comprehensive geriatric assessment,
      surgery, radiotherapy, and adjuvant therapy for early localized BC and of
      chemotherapy and targeted therapies for metastatic BC. Finally, we attempt to put
      into perspective the necessary balance between the expected benefits and risks,
      especially in the adjuvant setting. 

PMID- 25609936
TI  - Comparison of percentage body fat and body mass index for the prediction of
      inflammatory and atherogenic lipid risk profiles in elderly women.
AB  - OBJECTIVE: To compare the clinical classification of the body mass index (BMI)
      and percentage body fat (PBF) for the prediction of inflammatory and atherogenic
      lipid profile risk in older women. METHOD: Cross-sectional analytical study with
      277 elderly women from a local community in the Federal District, Brazil. PBF and
      fat-free mass (FFM) were determined by dual energy X-ray absorptiometry. The
      investigated inflammatory parameters were interleukin 6 and C-reactive protein.
      RESULTS: Twenty-five percent of the elderly women were classified as normal
      weight, 50% overweight, and 25% obese by the BMI. The obese group had higher
      levels of triglycerides and very low-density lipoproteins than did the normal
      weight group (P<=0.05) and lower levels of high-density lipoproteins (HDL) than
      did the overweight group (P<=0.05). According to the PBF, 49% of the elderly
      women were classified as eutrophic, 28% overweight, and 23% obese. In the
      binomial logistic regression analyses including age, FFM, and lipid profile, only
      FFM (odds ratio [OR]=0.809, 95% confidence interval [CI]: 0.739-0.886; P<0.0005)
      proved to be a predictor of reaching the eutrophic state by the BMI. When the
      cutoff points of PBF were used for the classification, FFM (OR=0.903, CI=0.884
      0.965; P=0.003) and the total cholesterol/HDL ratio (OR=0.113, CI=0.023-0.546;
      P=0.007) proved to be predictors of reaching the eutrophic state. CONCLUSION:
      Accurate identification of obesity, systemic inflammation, and atherogenic lipid
      profile is key to assessing the risk of cardiometabolic diseases. Classification
      based on dual energy X-ray absorptiometry measures, along with biochemical and
      inflammatory parameters, seems to have a great clinical importance, since it
      allows the lipid profile eutrophic distinction in elderly overweight women.

PMID- 25609938
TI  - Chloronychia: green nail syndrome caused by Pseudomonas aeruginosa in elderly
      persons.
AB  - Green nails, also known as chloronychia or green nail syndrome, are characterized
      by green discoloration of the nail plate (greenish-yellow, greenish-brown,
      greenish-black), proximal chronic non-tender paronychia, and distolateral
      onycholysis. The cause is Pseudomonas aeruginosa infection of the nail plate in
      persons whose hands are constantly exposed to water, soaps, and detergents or are
      subject to mechanical trauma, especially in the elderly. Green or black
      coloration of the nails should raise suspicion for Pseudomonas infection and be
      treated with an oral quinolone (ciprofloxacin), particularly in aged patients. We
      present three cases of green nails in elderly persons. 

PMID- 25609937
TI  - Stem cell therapies for age-related macular degeneration: the past, present, and
      future.
AB  - In the developed world, age-related macular degeneration (AMD) is one of the
      major causes of irreversible blindness in the elderly. Although management of
      neovascular AMD (wet AMD) has dramatically progressed, there is still no
      effective treatment for nonneovascular AMD (dry AMD), which is characterized by
      retinal pigment epithelial (RPE) cell death (or dysfunction) and
      microenvironmental disruption in the retina. Therefore, RPE replacement and
      microenvironmental regulation represent viable treatments for dry AMD. Recent
      advances in cell biology have demonstrated that RPE cells can be easily generated
      from several cell types (pluripotent stem cells, multipotent stem cells, or even
      somatic cells) by spontaneous differentiation, coculturing, defined factors or
      cell reprogramming, respectively. Additionally, in vivo studies also showed that
      the restoration of visual function could be obtained by transplanting functional
      RPE cells into the subretinal space of recipient. More importantly, clinical
      trials approved by the US government have shown promising prospects in RPE
      transplantation. However, key issues such as implantation techniques, immune
      rejection, and xeno-free techniques are still needed to be further investigated.
      This review will summarize recent advances in cell transplantation for dry AMD.
      The obstacles and prospects in this field will also be discussed. 

PMID- 25609939
TI  - Characterization of hepatic enzyme activity in older adults with dementia:
      potential impact on personalizing pharmacotherapy.
AB  - OBJECTIVE: To determine the frequency of pharmacogenomic variants and concurrent
      medications that may alter the efficacy and tolerability of acetylcholinesterase
      inhibitors (AChEIs). MATERIALS AND METHODS: A multisite cross-sectional study was
      carried out across four memory care practices in the greater Indianapolis area.
      Participants were adults aged 65 years and older with a diagnosis of probable or
      possible Alzheimer's disease (AD) (n=105). Blood samples and self-reported
      medication data were collected. Since two of the three AChEIs are metabolized by
      cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic
      variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity
      scores. Concurrent medication data were collected from self-reported medication
      surveys, and their predicted effect on the pharmacokinetics of AChEIs was
      determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities.
      RESULTS: Among the 105 subjects enrolled, 72% were female and 36% were African
      American. Subjects had a mean age of 79.6 years. The population used a mean of
      eight medications per day (prescription and nonprescription). The CYP2D6 activity
      score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and
      >2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or
      moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication
      considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the
      study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5
      enzymes due to either genetic variants or concomitant medications. CONCLUSION:
      Both pharmacogenetic variants and concurrent drug therapies that are predicted to
      alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD.
      Pharmacogenetic and drug-interaction data may help personalize AD therapy and
      increase adherence by improving tolerability.

PMID- 25609940
TI  - Efficacy and safety of once-daily glycopyrronium in predominantly Chinese
      patients with moderate-to-severe chronic obstructive pulmonary disease: the GLOW7
      study.
AB  - BACKGROUND: Glycopyrronium is a once-daily (od) long-acting muscarinic antagonist
      for the maintenance treatment of chronic obstructive pulmonary disease (COPD).
      The GLOW7 study evaluated the efficacy and safety of od glycopyrronium 50 MUg in
      predominantly Chinese patients with moderate-to-severe COPD. METHODS: In this 26
      week, multi-center, double-blind, placebo-controlled, parallel-group study, men
      and women >=40 years with moderate-to-severe COPD were randomized to
      glycopyrronium 50 MUg od or placebo (2:1). The primary objective was to confirm
      the significant improvement of trough forced expiratory volume in 1 second (FEV1)
      following 12 weeks of treatment with glycopyrronium compared with placebo.
      Secondary objectives included the effect of glycopyrronium on health status (St
      George's Respiratory Questionnaire), breathlessness (Transition Dyspnea Index),
      other lung function parameters, rescue medication use, and COPD exacerbations.
      Safety and tolerability were also evaluated. RESULTS: Of the 460 patients
      randomized, 459 were included in the full analysis set (glycopyrronium, n=306;
      placebo, n=154; mean age 64.7 years; mean post-bronchodilator FEV1: 50.8%
      predicted); 425 (92.4%) completed the study. At Week 12, glycopyrronium
      signifcantly improved trough FEV1 with a least square means treatment difference
      of 141 mL (95% confidence interval 111 mL, 171 mL; P<0.001) compared with
      placebo. The mean treatment effect of glycopyrronium was greater than the minimum
      clinically important difference versus placebo in both St George's Respiratory
      Questionnaire total score (-4.92; P<0.001) and Transition Dyspnea Index focal
      score (1.0; P<0.001) at week 26. Glycopyrronium reduced the risk of exacerbations
      in terms of time to first moderate or severe exacerbation by 28% (P=0.153) and
      rate of moderate or severe COPD exacerbation by 29% (P=0.119) compared with
      placebo. Incidence of death was 1.3% with glycopyrronium and 0% in placebo during
      the treatment period. Overall incidence of adverse events (glycopyrronium 43.6%;
      placebo 47.4%) and serious adverse events (glycopyrronium 5.6%; placebo 9.1%)
      were similar. CONCLUSION: In predominantly Chinese patients with moderate-to
      severe COPD, od glycopyrronium 50 MUg significantly improved lung function,
      dyspnea, and health status compared with placebo. The safety and tolerability
      profile of glycopyrronium was comparable to placebo.

PMID- 25609941
TI  - Questionnaire on switching from the tiotropium HandiHaler to the Respimat inhaler
      in patients with chronic obstructive pulmonary disease: changes in handling and
      preferences immediately and several years after the switch.
AB  - BACKGROUND: Tiotropium (Spiriva) is an inhaled muscarinic antagonist for patients
      with chronic obstructive pulmonary disease (COPD), and is available in two forms:
      the HandiHaler and the Respimat inhaler. The aim of this study was to investigate
      the handling of and preference for each device immediately after switching from
      the HandiHaler to the Respimat and 2-3 years after the switch. MATERIALS AND
      METHODS: The study comprised two surveys. A questionnaire was first administered
      to 57 patients with COPD (male:female 52:5, mean age 73.6+/-7.1 years) 8 weeks
      after switching from the HandiHaler (18 MUg) to the Respimat (5 MUg). A second
      similar but simplified questionnaire was administered to 39 of these patients who
      continued to use the Respimat and were available for follow-up after more than 2
      years. Pulmonary function was also measured during each period. RESULTS: In the
      first survey, 17.5% of patients preferred the HandiHaler, and 45.6% preferred the
      Respimat. There were no significant changes in pulmonary function or in the
      incidence of adverse events after the switch. In the second survey, performed 2-3
      years later, the self-assessed handling of the Respimat had significantly
      improved, and the number of patients who preferred the Respimat had increased to
      79.5%. CONCLUSION: The efficacy of the Respimat was similar to that of the
      HandiHaler. This was clear immediately after the switch, even in elderly patients
      with COPD who were long-term users of the HandiHaler. The preference for the
      Respimat increased with continued use.

PMID- 25609942
TI  - Symptoms and impact of COPD assessed by an electronic diary in patients with
      moderate-to-severe COPD: psychometric results from the SHINE study.
AB  - BACKGROUND: Symptoms, particularly dyspnea, and activity limitation, have an
      impact on the health status and the ability to function normally in patients with
      chronic obstructive pulmonary disease (COPD). METHODS: To develop an electronic
      patient diary (eDiary), qualitative patient interviews were conducted from 2009
      to 2010 to identify relevant symptoms and degree of bother due to symptoms. The
      eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in
      the 26-week QVA149 SHINE study. Two morning assessments (since awakening and
      since the last assessment) and one evening assessment were made each day.
      Assessments covered five symptoms ("shortness of breath," "phlegm/mucus," "chest
      tightness," "wheezing," and "coughing") and two impact items ("bothered by COPD"
      and "difficulty with activities") and were scored on a 10-point numeric scale.
      RESULTS: Patient compliance with the eDiary was 90.4% at baseline and 81.3% at
      week 26. Correlations between shortness of breath and impact items were >0.95.
      Regression analysis showed that shortness of breath was a highly significant
      (P<0.0001) predictor of impact items. Exploratory factor analysis gave a single
      factor comprising all eDiary items, including both symptoms and impact items.
      Shortness of breath, the total score (including five symptoms and two impact
      items), and the five-item symptom score from the eDiary performed well, with good
      consistency and reliability. The eDiary showed good sensitivity to change, with a
      0.6 points reduction in the symptoms scores (on a 0-10 point scale) representing
      a meaningful change. CONCLUSION: The eDiary was found to be valid, reliable, and
      responsive. The high correlations obtained between "shortness of breath" and the
      ratings of "bother" and "difficulty with activities" confirmed the relevance of
      this symptom in patients with COPD. Future studies will be required to explore
      further psychometric properties and their ability to differentiate between COPD
      treatments.

PMID- 25609944
TI  - Profile of inhaled glycopyrronium bromide as monotherapy and in fixed-dose
      combination with indacaterol maleate for the treatment of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality. The cornerstone of pharmacological treatment for COPD is
      bronchodilation. Inhaled glycopyrronium bromide is a long-acting muscarinic
      antagonist developed as a maintenance treatment for patients with COPD. Phase III
      trials have shown that glycopyrronium produces rapid and sustained
      bronchodilation with an efficacy similar to tiotropium and is well tolerated,
      with a low incidence of muscarinic side effects in patients with moderate to
      severe COPD. A combination of glycopyrronium bromide with indacaterol maleate
      (QVA149) has recently been approved as a once-daily maintenance therapy in adult
      patients with COPD. Phase III trials (the IGNITE program) with QVA149 have
      demonstrated significant improvements in lung function versus placebo,
      glycopyrronium, and tiotropium in patients with moderate to severe COPD, with no
      safety concerns of note. Hence QVA149 is a safe treatment option for moderate to
      severe COPD patients in whom long-acting muscarinic antagonist monotherapy is
      inadequate. 

PMID- 25609943
TI  - Managing comorbidities in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and
      mortality worldwide. Age and smoking are common risk factors for COPD and other
      illnesses, often leading COPD patients to demonstrate multiple coexisting
      comorbidities. COPD exacerbations and comorbidities contribute to the overall
      severity in individual patients. Clinical trials investigating the treatment of
      COPD routinely exclude patients with multiple comorbidities or advanced age.
      Clinical practice guidelines for a specific disease do not usually address
      comorbidities in their recommendations. However, the management and the medical
      intervention in COPD patients with comorbidities need a holistic approach that is
      not clearly established worldwide. This holistic approach should include the
      specific burden of each comorbidity in the COPD severity classification scale.
      Further, the pharmacological and nonpharmacological management should also
      include optimal interventions and risk factor modifications simultaneously for
      all diseases. All health care specialists in COPD management need to work
      together with professionals specialized in the management of the other major
      chronic diseases in order to provide a multidisciplinary approach to COPD
      patients with multiple diseases. In this review, we focus on the major
      comorbidities that affect COPD patients. We present an overview of the problems
      faced, the reasons and risk factors for the most commonly encountered
      comorbidities, and the burden on health care costs. We also provide a rationale
      for approaching the therapeutic options of the COPD patient afflicted by
      comorbidity. 

PMID- 25609945
TI  - EGLN2 and RNF150 genetic variants are associated with chronic obstructive
      pulmonary disease risk in the Chinese population.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major and an
      increasingly prevalent health problem worldwide. It has been reported that
      genetic variation may play a role in the development and severity of COPD. The
      purpose of this study was to investigate whether single nucleotide polymorphisms
      in multiple genetic variants were associated with COPD in a Chinese population
      from Hainan province. METHODS: In this case-control study, including 200 COPD
      patients and 401 controls, we genotyped 14 tag single nucleotide polymorphisms
      and evaluated their association with COPD using the chi (2) test and genetic
      model analysis. RESULTS: The polymorphism, rs10007052, in the RNF150 gene was
      significantly associated with COPD risk at a 5% level (odds ratio =1.43, 95%
      confidence interval, 1.06-1.95, P=0.020). In the log-additive model, the minor
      allele (C) of rs10007052 in the RNF150 gene (P=0.026) and the minor allele (C) of
      rs3733829 in the EGLN2 gene (P=0.037) were associated with COPD risk after
      adjustment for age, sex, and smoking status. Further haplotype analysis revealed
      that the "CT" haplotype composed of the mutant allele (C) of rs7937, rs3733829 in
      the EGLN2 gene, was associated with increased COPD risk (odds ratio =1.55; 95%
      confidence interval, 1.05-2.31; P=0.029). CONCLUSION: Our findings indicated that
      rs10007052 in the RNF150 and rs3733829 in the EGLN2 gene were significantly
      associated with the risk of COPD in Chinese populations of Hainan province. These
      data may provide novel insights into the pathogenesis of COPD, although further
      studies with larger numbers of participants worldwide are needed for validation
      of our conclusions.

PMID- 25609946
TI  - Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on
      hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene
      glycol 1000 succinate for tumor-targeted delivery of morin hydrate.
AB  - Herein, we describe the preparation of a targeted cellular delivery system for
      morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl
      cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic
      effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was
      mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA "plain"
      nanoparticle (MH-PNs) and HA-PBCA/TPGS "mixed" nanoparticles (MH-MNs) were
      concomitantly characterized in terms of loading efficiency, particle size, zeta
      potential, critical aggregation concentration, and morphology. The obtained MH
      PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential
      and a particle size less than 200 nm, favorable for drug targeting. Remarkably,
      the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in
      vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of
      MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs
      containing TPGS exhibited selective cytotoxic effects against cancer cells
      without diminishing the viability of normal cells. In addition, the cellular
      uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than
      that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the
      internalization pathway studies suggested that the internalization mechanism of
      the nanoparticles was mediated mainly by the CD44 receptors through a clathrin
      dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo
      antitumor potency and induced more tumor cell apoptosis than did MH-PNs,
      following intravenous administration to S180 tumor-bearing mice. Overall, the
      results imply that the developed nanoparticles are promising vehicles for the
      targeted delivery of lipophilic anticancer drugs. 

PMID- 25609947
TI  - Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle
      size, formulation stability, and in-vivo efficacy.
AB  - Cationic charged chitosan as stabilizer was evaluated in preparation of
      nanocrystals using probe sonication method. The influence of cationic charge
      densities of chitosan (low CS(L), medium CS(M), high CS(H) molecular weights) and
      Labrasol((r)) in solubility enhancement and modifying the release was
      investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to
      CS(M) and CS(H); low cationic charge of CS(L) acted as both electrostatic and
      steric stabilizer by significant size reduction to 394 nm with charge of 21.5
      meV. Solubility of ATR-CS(L) increased to 60-fold relative to pure ATR and ATR-L.
      Nanocrystals were characterized for physiochemical properties. Scanning electron
      microscopy revealed scaffold-like structures with high surface area. X-ray powder
      diffractometry and differential scanning calorimetry revealed crystalline to
      slight amorphous state changes after cationic charge size reduction. Fourier
      transform-infrared spectra indicated no potent drug-excipient interactions. The
      enhanced dissolution profile of ATR-CS(L) indicates that sustained release was
      achieved compared with ATR-L and Lipitor((r)). Anti-hyperlipidemic performance
      was pH dependent where ATR-CS(L) exhibited 2.5-fold higher efficacy at pH 5
      compared to pH 6 and Lipitor((r)). Stability studies indicated marked changes in
      size and charge for ATR-L compared to ATR-CS(L) exemplifying importance of the
      stabilizer. Therefore, nanocrystals developed with CS(L) as a stabilizer is a
      promising choice to enhance dissolution, stability, and in-vivo efficacy of major
      Biopharmaceutical Classification System II/IV drugs.

PMID- 25609948
TI  - Passive tumor targeting and imaging by using mercaptosuccinic acid-coated near
      infrared quantum dots.
AB  - In this paper, we demonstrate the preparation of monodispersed quantum dots (QDs)
      as near-infrared (NIR) optical probes for in vivo pancreatic cancer targeting and
      imaging. The design of these luminescent probes involves functionalizing NIR QDs
      with ligand mercaptosuccinic acid (MSA), which targets the tumor site by enhanced
      permeability and retention effect. The colloidal and optical stability of the QDs
      can be maintained for >1 week. In vivo optical imaging studies in nude mice
      bearing pancreatic tumor show that the probes accumulate at tumor sites for >2.5
      hours following intravenous injection of the functionalized NIR QDs. Tumor
      labeling studies showed no evidence of harmful effects on the treated animals,
      even at a dose as high a ~50 mg/kg. These results demonstrate that the engineered
      MSA-functionalized QDs can serve as a diagnostic platform for early detection of
      cancer, as well as in image-guided precise surgical resection of tumors. 

PMID- 25609949
TI  - Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic
      co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) is a common skin cancer, and its
      treatment is still difficult. The aim of this study was to evaluate the
      effectiveness of nanoparticle (NP)-assisted 5-aminolevulinic acid (ALA) delivery
      for topical photodynamic therapy (PDT) of cutaneous SCC. MATERIALS AND METHODS:
      Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded
      polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The
      kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs,
      therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined.
      RESULTS: PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP
      mediated topical PDT was more effective than free ALA of the same concentration
      in treating cutaneous SCC. CONCLUSION: PLGA NPs provide a promising strategy for
      delivering ALA in topical PDT of cutaneous SCC.

PMID- 25609950
TI  - Cationic additives in nanosystems activate cytotoxicity and inflammatory response
      of human neutrophils: lipid nanoparticles versus polymeric nanoparticles.
AB  - This report compares the effect of lipid and polymeric nanoparticles upon human
      neutrophils in the presence of cationic surfactants. Nanostructured lipid
      carriers and poly(lactic-co-glycolic) acid nanoparticles were manufactured as
      lipid and polymeric systems, respectively. Some cytotoxic and proinflammatory
      mediators such as lactate dehydrogenase (LDH), elastase, O2(*-), and
      intracellular Ca(2+) were examined. The nanoparticles showed a size of 170-225
      nm. Incorporation of cetyltrimethylammonium bromide or soyaethyl morpholinium
      ethosulfate, the cationic surfactant, converted zeta potential from a negative to
      a positive charge. Nanoparticles without cationic surfactants revealed a
      negligible change on immune and inflammatory responses. Cationic surfactants in
      both nanoparticulate and free forms induced cell death and the release of
      mediators. Lipid nanoparticles generally demonstrated a greater response compared
      to polymeric nanoparticles. The neutrophil morphology observed by electron
      microscopy confirmed this trend. Cetyltrimethylammonium bromide as the coating
      material showed more significant activation of neutrophils than soyaethyl
      morpholinium ethosulfate. Confocal microscope imaging displayed a limited
      internalization of nanoparticles into neutrophils. It is proposed that cationic
      nanoparticles interact with the cell membrane, triggering membrane disruption and
      the following Ca(2+) influx. The elevation of intracellular Ca(2+) induces
      degranulation and oxidative stress. The consequence of these effects is
      cytotoxicity and cell death. Caution should be taken when selecting feasible
      nanoparticulate formulations and cationic additives for consideration of
      applicability and toxicity.

PMID- 25609951
TI  - Molecular photoacoustic imaging of breast cancer using an actively targeted
      conjugated polymer.
AB  - Conjugated polymers (CPs) are upcoming optical contrast agents in view of their
      unique optical properties and versatile synthetic chemistry. Biofunctionalization
      of these polymer-based nanoparticles enables molecular imaging of biological
      processes. In this work, we propose the concept of using a biofunctionalized CP
      for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In
      particular, after verifying the PA activity of a CP nanoparticle (CP dots) in
      phantoms and the targeting efficacy of a folate-functionalized version of the
      same (folate-CP dots) in vitro, we systemically administered the probe into a
      folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to
      demonstrate the possible application of folate-CP dots for imaging FR+ve breast
      cancers in comparison to CP dots with no folate moieties. We observed a strong PA
      signal at the tumor site of folate-CP dots-administered mice as early as 1 hour
      after administration as a result of the active targeting of the folate-CP dots to
      the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots
      administered mice as a result of the passive accumulation of the probe by
      enhanced permeability and retention effect. We also observed that folate-CP dots
      produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP
      dots. These observations demonstrate the great potential of this active-targeting
      CP to be used as a contrast agent for molecular PA diagnostic imaging in various
      biomedical applications. 

PMID- 25609952
TI  - Detection of a fluorescent-labeled avidin-nucleic acid nanoassembly by confocal
      laser endomicroscopy in the microvasculature of chronically inflamed intestinal
      mucosa.
AB  - Inflammatory bowel diseases are chronic gastrointestinal pathologies causing
      great discomfort in both children and adults. The pathogenesis of inflammatory
      bowel diseases is not yet fully understood and their diagnosis and treatment are
      often challenging. Nanoparticle-based strategies have been tested in local drug
      delivery to the inflamed colon. Here, we have investigated the use of the novel
      avidin-nucleic acid nanoassembly (ANANAS) platform as a potential diagnostic
      carrier in an experimental model of inflammatory bowel diseases. Fluorescent-
      labeled ANANAS nanoparticles were administered to mice with chemically induced
      chronic inflammation of the large intestine. Localization of mucosal
      nanoparticles was assessed in vivo by dual-band confocal laser endomicroscopy.
      This technique enables characterization of the mucosal microvasculature and crypt
      architecture at subcellular resolution. Intravascular nanoparticle distribution
      was observed in the inflamed mucosa but not in healthy controls, demonstrating
      the utility of the combination of ANANAS and confocal laser endomicroscopy for
      highlighting intestinal inflammatory conditions. The specific localization of
      ANANAS in inflamed tissues supports the potential of this platform as a targeted
      carrier for bioactive moieties in the treatment of inflammatory bowel disease. 

PMID- 25609953
TI  - Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis
      polysaccharide in both myocardial infarction and ischemia/reperfusion rats.
AB  - Although PEGylation plays an important role in drug delivery, knowledge about the
      distribution behavior of PEGylated drugs in ischemic myocardia is rather limited
      compared to nanoparticles. This work therefore aims to characterize the targeting
      behavior of the anti-myocardial ischemic mono-PEGylated conjugates of Radix
      Ophiopogonis polysaccharide (ROP) in two clinically relevant animal models, ie,
      the myocardial infarction (MI) model and the ischemia/reperfusion (IR) model. To
      determine the effect of the molecular size of conjugates, two representative
      conjugates (20- and 40-kDa polyethylene glycol mono-modified ROPs), with
      hydrodynamic size being approximately and somewhat beyond 10 nm, respectively,
      were studied in parallel at three time points postdose after a method for
      determining them quantitatively in biosamples was established. The results showed
      that the cardiac distribution of the two conjugates was significantly enhanced in
      both MI and IR rats due to the enhanced permeability and retention effect induced
      by ischemia. In general, the cardiac targeting efficacy of the conjugates in MI
      and IR rats was approximately 2; however, different changing in targeting
      efficacy with time was observed between MI and IR rats and also between the
      conjugates. Although the enhanced permeability and retention effect-based
      targeting efficacy for mono-PEGylated ROPs was not high, they, as dissolved
      macromolecules, are prone to diffusion in the cardiac interstitium space, and
      thus, facilitate the drug to reach perfusion-deficient and nonperfused areas.
      These findings are helpful in choosing the cardiac targeting strategy. 

PMID- 25609954
TI  - Effective near-infrared photodynamic therapy assisted by upconversion
      nanoparticles conjugated with photosensitizers.
AB  - A drug model photosensitizer-conjugated upconversion nanoparticles nanocomplex
      was explored for application in near-infrared photodynamic therapy. As near
      infrared penetrates deeper into the tissue, the model is useful for the
      application of photodynamic therapy in deeper tissue. The nanocomplex that was
      synthesized had low polydispersity, and the upconversion nanoparticle was
      covalently conjugated with the photosensitizer. The robust bond could prevent the
      undesired premature release of photosensitizer and also enhance the singlet
      oxygen generation. Singlet-oxygen generation rate from this nanocomplex was
      evaluated in solution. The photodynamic therapy effect was assessed with MCF-7
      cells in two different methods, 3-(4,5-dimethylth-iazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and live/dead assay. The assay results
      showed that promising efficacy (>90%) can be achieved with a low concentration
      (50 MUg mL(-1)) of this nanocomplex and mild dosage (7 mW cm(-2)) of near
      infrared laser treatment. 

PMID- 25609955
TI  - Barium titanate nanoparticles and hypergravity stimulation improve
      differentiation of mesenchymal stem cells into osteoblasts.
AB  - BACKGROUND: Enhancement of the osteogenic potential of mesenchymal stem cells
      (MSCs) is highly desirable in the field of bone regeneration. This paper proposes
      a new approach for the improvement of osteogenesis combining hypergravity with
      osteoinductive nanoparticles (NPs). MATERIALS AND METHODS: In this study, we
      aimed to investigate the combined effects of hypergravity and barium titanate NPs
      (BTNPs) on the osteogenic differentiation of rat MSCs, and the hypergravity
      effects on NP internalization. To obtain the hypergravity condition, we used a
      large-diameter centrifuge in the presence of a BTNP-doped culture medium. We
      analyzed cell morphology and NP internalization with immunofluorescent staining
      and coherent anti-Stokes Raman scattering, respectively. Moreover, cell
      differentiation was evaluated both at the gene level with quantitative real-time
      reverse-transcription polymerase chain reaction and at the protein level with
      Western blotting. RESULTS: Following a 20 g treatment, we found alterations in
      cytoskeleton conformation, cellular shape and morphology, as well as a
      significant increment of expression of osteoblastic markers both at the gene and
      protein levels, jointly pointing to a substantial increment of NP uptake. Taken
      together, our findings suggest a synergistic effect of hypergravity and BTNPs in
      the enhancement of the osteogenic differentiation of MSCs. CONCLUSION: The
      obtained results could become useful in the design of new approaches in bone
      tissue engineering, as well as for in vitro drug-delivery strategies where an
      increment of nanocarrier internalization could result in a higher drug uptake by
      cell and/or tissue constructs.

PMID- 25609956
TI  - Characterization of the host-guest complex of a curcumin analog with beta
      cyclodextrin and beta-cyclodextrin-gemini surfactant and evaluation of its
      anticancer activity.
AB  - BACKGROUND: Curcumin analogs, including the novel compound NC 2067, are potent
      cytotoxic agents that suffer from poor solubility, and hence, low
      bioavailability. Cyclodextrin-based carriers can be used to encapsulate such
      agents. In order to understand the interaction between the two molecules, the
      physicochemical properties of the host-guest complexes of NC 2067 with beta
      cyclodextrin (CD) or beta-cyclodextrin-gemini surfactant (CDgemini surfactant)
      were investigated for the first time. Moreover, possible supramolecular
      structures were examined in order to aid the development of new drug delivery
      systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067
      with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell
      line. METHODS: Physicochemical properties of the complexes formed of NC 2067 with
      CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray
      diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric
      analysis. Synchrotron-based small- and wide-angle X-ray scattering and size
      measurements were employed to assess the supramolecular morphology of the complex
      formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of
      the formulations toward A375 melanoma cells at various drug-to-carrier mole
      ratios were measured by cell viability assay. RESULTS: Physical mixtures of NC
      2067 and CD or CDgemini surfactant showed characteristics of the individual
      components, whereas the complex of NC 2067 and CD or CDgemini surfactant
      presented new structural features, supporting the formation of the host-guest
      complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles
      having sizes of 100-200 nm. NC 2067 retained its anticancer activity in the
      complex with CDgemini surfactant for different drug-to-carrier mole ratios, with
      an IC50 (half-maximal inhibitory concentration) value comparable to that for NC
      2067 without the carrier. CONCLUSION: The formation of host-guest complexes of NC
      2067 with CD or CDgemini surfactant has been confirmed and hence the CDgemini
      surfactant shows good potential to be used as a delivery system for anticancer
      agents.

PMID- 25609957
TI  - BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction
      and osteogenicity in large bone defects.
AB  - The regeneration of large bone defects is an osteoinductive, osteoconductive, and
      osteogenic process that often requires a bone graft for support. Limitations
      associated with naturally autogenic or allogenic bone grafts have demonstrated
      the need for synthetic substitutes. The present study investigates the
      feasibility of using novel hollow hydroxyapatite microspheres as an
      osteoconductive matrix and a carrier for controlled local delivery of bone
      morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration.
      Hollow hydroxyapatite microspheres (100+/-25 MUm) with a core (60+/-18 MUm) and a
      mesoporous shell (180+/-42 m(2)/g surface area) were prepared by a glass
      conversion technique and loaded with recombinant human BMP2 (1 MUg/mg). There was
      a gentle burst release of BMP2 from microspheres into the surrounding phosphate
      buffered saline in vitro within the initial 48 hours, and continued at a low rate
      for over 40 days. In comparison with hollow hydroxyapatite microspheres without
      BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite
      microspheres had a significantly enhanced capacity to reconstitute radial bone
      defects in rabbit, as shown by increased serum alkaline phosphatase; quick and
      complete new bone formation within 12 weeks; and great biomechanical flexural
      strength. These results indicate that BMP2-loaded hollow hydroxyapatite
      microspheres could be a potential new option for bone graft substitutes in bone
      regeneration. 

PMID- 25609958
TI  - Molecular plasma deposition: biologically inspired nanohydroxyapatite coatings on
      anodized nanotubular titanium for improving osteoblast density.
AB  - In order to begin to prepare a novel orthopedic implant that mimics the natural
      bone environment, the objective of this in vitro study was to synthesize
      nanocrystalline hydroxyapatite (NHA) and coat it on titanium (Ti) using molecular
      plasma deposition (MPD). NHA was synthesized through a wet chemical process
      followed by a hydrothermal treatment. NHA and micron sized hydroxyapatite (MHA)
      were prepared by processing NHA coatings at 500 degrees C and 900 degrees C,
      respectively. The coatings were characterized before and after sintering using
      scanning electron microscopy, atomic force microscopy, and X-ray diffraction. The
      results revealed that the post-MPD heat treatment of up to 500 degrees C
      effectively restored the structural and topographical integrity of NHA. In order
      to determine the in vitro biological responses of the MPD-coated surfaces, the
      attachment and spreading of osteoblasts (bone-forming cells) on the uncoated, NHA
      coated, and MHA-coated anodized Ti were investigated. Most importantly, the NHA
      coated substrates supported a larger number of adherent cells than the MHA-coated
      and uncoated substrates. The morphology of these cells was assessed by scanning
      electron microscopy and the observed shapes were different for each substrate
      type. The present results are the first reports using MPD in the framework of
      hydroxyapatite coatings on Ti to enhance osteoblast responses and encourage
      further studies on MPD-based hydroxyapatite coatings on Ti for improved
      orthopedic applications. 

PMID- 25609959
TI  - Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive
      differentiation of benign and malignant breast tumors.
AB  - The capability of saliva protein analysis, based on membrane protein purification
      and surface-enhanced Raman spectroscopy (SERS), for detecting benign and
      malignant breast tumors is presented in this paper. A total of 97 SERS spectra
      from purified saliva proteins were acquired from samples obtained from three
      groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31
      patients with malignant breast tumors. Subtle but discernible changes in the mean
      SERS spectra of the three groups were observed. Tentative assignments of the
      saliva protein SERS spectra demonstrated that benign and malignant breast tumors
      led to several specific biomolecular changes of the saliva proteins. Multiclass
      partial least squares-discriminant analysis was utilized to analyze and classify
      the saliva protein SERS spectra from healthy subjects, benign breast tumor
      patients, and malignant breast tumor patients, yielding diagnostic sensitivities
      of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and
      86.36%, respectively. The results from this exploratory work demonstrate that
      saliva protein SERS analysis combined with partial least squares-discriminant
      analysis diagnostic algorithms has great potential for the noninvasive and label
      free detection of breast cancer. 

PMID- 25609960
TI  - Oxidative stress and antibacterial properties of a graphene oxide-cystamine
      nanohybrid.
AB  - Oxidative stress can damage proteins, DNA, and lipids, and is involved in the
      progression of many diseases. Damage to infected cells caused by oxidative stress
      is related to increased levels of reactive oxygen species, including hydrogen
      peroxide. During oxidative stress, hydrogen peroxide levels are often increased
      and catalase level decreased inside cells. This can lead to the death of skin and
      other cells. Hydrophobic low molecular weight compounds are useful in treating
      hemorrhagic conditions of the skin. To this end, cystamine has been successfully
      conjugated with graphene oxide (GO) as a drug carrier. The current study used the
      microdilution method to determine the minimum inhibitory concentrations of
      cystamine-conjugated GO against four types of pathogenic bacteria. Minimum
      inhibitory concentrations values were 1 MUg/mL against Escherichia coli and
      Salmonella typhimurium, 6 MUg/mL against Enterococcus faecalis, and 4 MUg/mL
      against Bacillus subtilis. Toxicity of the conjugate against squamous cell
      carcinoma 7 cells was minimal at low concentrations, but increased in a dose
      dependent manner. These results demonstrated that our protocol produced a
      cystamine-conjugated GO with low cytotoxicity, but strong reactive oxygen species
      effects and high antibacterial activity. This nanohybrid may be useful in the
      treatment of dermatological disorders. Moreover, this class of nanohybrid may
      have other biomedical applications due to their low cytotoxicity and high
      antibacterial activity. 

PMID- 25609961
TI  - PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance
      antitumor efficacy via intrinsic apoptosis pathway.
AB  - Chemotherapy offers a systemic cancer treatment; however, it is limited in
      clinical administration due to its serious side effects. In cancer medicine, the
      use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release
      anticancer drug at the specific site and reduce the incidence of toxicity in
      normal tissues. In the present study, we aimed to evaluate the benefit of a novel
      chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded
      into poly (lactic-co-glycolic acid) (PLGA)-poly-L-lysine (PLL)-polyethylene
      glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR
      loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR
      loaded NPs, the leukemia K562 cells were collected and the intracellular
      concentration of DNR was detected by flow cytometry, respectively. Furthermore,
      the effect of drugs on the growth of tumors in K562 xenografts was observed and
      the relevant toxicity of therapeutic drugs on organs was investigated in vivo.
      Meanwhile, cell apoptosis in the excised xenografts was measured by transferase
      mediated dUTP nick-end labeling assay, and the expression of apoptosis-related
      proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was
      determined by Western blotting analysis. Results showed that DNR-loaded NPs
      increased intracellular concentration of DNR in K562 cells in vitro and induced a
      remarkable improvement in anticancer activity in the xenografts in vivo. The
      expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase
      3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs
      group than that in other ones. Interestingly, pathological assessment showed no
      apparent damage to the main organs. In summary, the results obtained from this
      study showed that the novel NPs DDS could improve the efficacy of DNR in the
      treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be
      inferred that the new drug delivery may be a useful clinical tool.

PMID- 25609962
TI  - Response of human mesenchymal stem cells to intrafibrillar nanohydroxyapatite
      content and extrafibrillar nanohydroxyapatite in biomimetic chitosan/silk
      fibroin/nanohydroxyapatite nanofibrous membrane scaffolds.
AB  - Incorporation of nanohydroxyapatite (nHAP) within a chitosan (CS)/silk fibroin
      (SF) nanofibrous membrane scaffold (NMS) may provide a favorable microenvironment
      that more closely mimics the natural bone tissue physiology and facilitates
      enhanced osteogensis of the implanted cell population. In this study, we prepared
      pristine CS/SF NMS, composite CS/SF/nHAP NMS containing intrafibrillar nHAP by in
      situ blending of 10% or 30% nHAP before the electrospinning step, and composite
      CS/SF/nHAP NMS containing extrafibrillar nHAP by depositing 30% nHAP through
      alternative soaking surface mineralization. We investigated the effect of the
      incorporation of HAP nanoparticles on the physicochemical properties of pristine
      and composite NMS. We confirmed the presence of ~30 nm nHAP in the composite
      nanofibrous membranes by thermogravimetry analysis (TGA), X-ray diffraction
      (XRD), and scanning electron microscopy (SEM), either embedded in or exposed on
      the nanofiber. Nonetheless, the alternative soaking surface mineralization method
      drastically influenced the mechanical properties of the NMS with 88% and 94% drop
      in Young's modulus and ultimate maximum stress. Using in vitro cell culture
      experiments, we investigated the effects of nHAP content and location on
      proliferation and osteogenic differentiation of human bone marrow mesenchymal
      stem cells (hMSCs). The proliferation of hMSCs showed no significant difference
      among pristine and composite NMS. However, the extent of osteogenic
      differentiation of hMSCs was found to be positively correlated with the content
      of nHAP in the NMS, while its location within the nanofiber played a less
      significant role. In vivo experiments were carried out with hMSCs seeded in
      CS/SF/30%nHAP NMS prepared by in situ blending and subcutaneous implantation in
      nude mice. Micro-computed tomography images as well as histological and
      immunohistochemical analysis of the retrieved hMSCs/NMS construct 1 and 2 months
      postimplantation indicated that NMS had the potential for bone regeneration and
      can be suggested as a promising scaffold for bone tissue engineering. 

PMID- 25609963
TI  - Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug
      compound methyl dihydrojasmonate.
AB  - Methyl dihydrojasmonate (MJ) has been studied because of its application as an
      antitumor drug compound. However, as MJ is a poorly water-soluble compound, a
      suitable oil-in-water microemulsion (ME) has been studied in order to provide its
      solubilization in an aqueous media and to allow its administration by the
      parenteral route. The ME used in this work was characterized on the pseudo
      ternary phase diagram by dynamic light scattering and rheological measurements.
      Regardless of the drug presence, the droplet size was directly dependent on the
      oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME
      significantly increased the ME diameter, mainly at low O/S ratios. The
      rheological evaluation of the systems showed that in the absence of drug a
      Newtonian behavior was observed. On the other hand, in the presence of MJ the ME
      systems revealed pseudoplastic behavior, independently of the O/S ratio. The in
      vivo studies demonstrated that not only was the effect on the tumor inhibition
      inversely dependent on the MJ-loaded ME administered dose, but also it was
      slightly higher than the doxorubicin alone, which was used as the positive
      control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found
      at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at
      doses higher than 350 mg/kg, which was higher than the dose that provides tumor
      inhibition effect in this study. Because the MJ-loaded ME was shown to have
      anticancer activity comparable to doxorubicin, the ME described here may be
      considered a suitable vehicle for parenteral administration of MJ. 

PMID- 25609964
TI  - Stability and toxicity of empty or gene-loaded lipopolysaccharide-amine
      nanopolymersomes.
AB  - Successful in vivo gene delivery mediated by nonviral vectors requires efficient
      extracellular and intracellular gene delivery, but few studies have given
      attention to the former. That is why numerous gene delivery systems have
      succeeded in vitro, while the expected clinical success has not come about. To
      realize efficient extracellular gene delivery, the stability of vectors and/or
      their complexes with genes in body fluids is first required, which prevents
      loaded genes from premature unloading and degradation. Furthermore, the storage
      stability of vectors under common conditions is important for their widespread
      applications. Lipopolysaccharide-amine nanopolymersomes (NPs), a gene vector
      developed by our group recently, have higher than 95% in vitro transfection
      efficiency in mesenchymal stem cells when delivering pEGFP, and induce
      significant angiogenesis in zebrafish when delivering plasmid encoding vascular
      endothelial growth factor deoxyribonucleic acid (pVEGF). To reveal their
      extracellular delivery ability and storage stability, in this study their
      stability in various simulant physiological environments and storage conditions
      was systematically studied by monitoring their changes in disassembly, size, zeta
      potential, and transfection efficiency. Additionally, damage to the mitochondria
      of mesenchymal stem cells was evaluated. Results show that NPs and plasmid
      deoxyribonucleic acid (pDNA)-loaded NPs (pNPs) have acceptable stability against
      dilution, anions, salts, pH, enzyme, and serum, presumably assuring their
      efficient extracellular delivery in vivo. Moreover, both the lyophilized NPs at
      room temperature and NP/pNP solution at 4 degrees C have high storage stability,
      and pNPs show low damage to the mitochondria. The acceptable stability of NPs
      combined with compatibility and efficient gene transfection highlight their huge
      potential in the clinic as a gene delivery vector. 

PMID- 25609965
TI  - Lower irritation microemulsion-based rotigotine gel: formulation optimization and
      in vitro and in vivo studies.
AB  - BACKGROUND: Rotigotine is a potent and selective D1, D2, and D3 dopaminergic
      receptor agonist. Due to an extensive first-pass effect, it has a very low oral
      bioavailability (approximately 0.5% in rats). PURPOSE: The present investigation
      aimed to develop a microemulsion-based hydrogel for transdermal rotigotine
      delivery with lower application site reactions. METHODS: Pseudoternary phase
      diagrams were constructed to determine the region of oil in water (o/w)-type
      microemulsion. Central composite design was used to support the pseudoternary
      phase diagrams and to select homogeneous and stable microemulsions with an
      optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation
      experiments were performed, using Franz diffusion cells, to compare rotigotine
      loaded microemulsions with rotigotine solutions in oil. The optimized formulation
      was used to prepare a microemulsion-based hydrogel, which was subjected to
      bioavailability and skin irritancy studies. RESULTS: The selected formulations of
      rotigotine-loaded microemulsions had enhanced flux and permeation coefficients
      compared with rotigotine in oil. The optimum microemulsion contained 68% water,
      6.8% Labrafil((r)), 13.44% Cremophor((r)) RH40, 6.72% Labrasol((r)), and 5.04%
      Transcutol((r)) HP; the drug-loading rate was 2%. To form a microemulsion gel, 1%
      Carbomer 1342 was added to the microemulsion. The bioavailability of the
      rotigotine-loaded microemulsion gel was 105.76%+/-20.52% with respect to the
      marketed rotigotine patch (Neupro((r))). The microemulsion gel irritated the skin
      less than Neupro. CONCLUSION: A rotigotine microemulsion-based hydrogel was
      successfully developed, and an optimal formulation for drug delivery was
      identified. This product could improve patient compliance and have broad
      marketability.

PMID- 25609966
TI  - Protein immobilization onto electrochemically synthesized CoFe nanowires.
AB  - CoFe nanowires have been synthesized by the electrodeposition technique into the
      pores of a polycarbonate membrane with a nominal pore diameter of 50 nm, and the
      composition of CoFe nanowires varying by changing the source concentration of
      iron. The synthesized nanowire surfaces were functionalized with amine groups by
      treatment with aminopropyltriethoxysilane (APTES) linker, and then conjugated
      with streptavidin-Cy3 protein via ethyl (dimethylaminopropyl) carbodiimide and N
      hydroxysuccinimide coupling chemistry. The oxide surface of CoFe nanowire is
      easily modified with aminopropyltriethoxysilane to form an amine terminating
      group, which is covalently bonded to streptavidin-Cy3 protein. The
      physicochemical properties of the nanowires were analyzed through different
      characterization techniques such as scanning electron microscope, energy
      dispersive spectroscopy, and vibrating sample magnetometer. Fluorescence
      microscopic studies and Fourier transform infrared studies confirmed the
      immobilization of protein on the nanowire surface. In addition, the transmission
      electron microscope analysis reveals the thin protein layer which is around 12-15
      nm on the nanowire surfaces. 

PMID- 25609967
TI  - Ag-plasma modification enhances bone apposition around titanium dental implants:
      an animal study in Labrador dogs.
AB  - Dental implants with proper antibacterial ability as well as ideal
      osseointegration are being actively pursued. The antimicrobial ability of
      titanium implants can be significantly enhanced via modification with silver
      nanoparticles (Ag NPs). However, the high mobility of Ag NPs results in their
      potential cytotoxicity. The silver plasma immersion ion-implantation (Ag-PIII)
      technique may remedy the defect. Accordingly, Ag-PIII technique was employed in
      this study in an attempt to reduce the mobility of Ag NPs and enhance
      osseointegration of sandblasted and acid-etched (SLA) dental implants. Briefly,
      48 dental implants, divided equally into one control and three test groups
      (further treated by Ag-PIII technique with three different implantation
      parameters), were inserted in the mandibles of six Labrador dogs. Scanning
      electron microscopy, X-ray photoelectron spectroscopy, and inductively coupled
      plasma optical emission spectrometry were used to investigate the surface
      topography, chemical states, and silver release of SLA- and Ag-PIII-treated
      titanium dental implants. The implant stability quotient examination,
      Microcomputed tomography evaluation, histological observations, and
      histomorphometric analysis were performed to assess the osseointegration effect
      in vivo. The results demonstrated that normal soft tissue healing around dental
      implants was observed in all the groups, whereas the implant stability quotient
      values in Ag-PIII groups were higher than that in the SLA group. In addition, all
      the Ag-PIII groups, compared to the SLA-group, exhibited enhanced new bone
      formation, bone mineral density, and trabecular pattern. With regard to
      osteogenic indicators, the implants treated with Ag-PIII for 30 minutes and 60
      minutes, with the diameter of the Ag NPs ranging from 5-25 nm, were better than
      those treated with Ag-PIII for 90 minutes, with the Ag NPs diameter out of that
      range. These results suggest that Ag-PIII technique can reduce the mobility of Ag
      NPs and enhance the osseointegration of SLA surfaces and have the potential for
      future use. 

PMID- 25609968
TI  - Factors associated with the risk of relapse in schizophrenic patients after a
      response to electroconvulsive therapy: a retrospective study.
AB  - PURPOSE: Electroconvulsive therapy (ECT) is an effective treatment for depression
      and schizophrenia. However, there is a high rate of relapse after an initial
      response to ECT, even with antidepressant or antipsychotic maintenance therapy.
      This study was carried out to examine the factors that influence the risk of
      relapse in schizophrenic patients after a response to ECT. PATIENTS AND METHODS:
      We retrospectively reviewed the records of 43 patients with schizophrenia who
      received and responded to an acute ECT course. We analyzed the associated
      clinical variables and relapse after response to the acute ECT. Relapse was
      defined as a Clinical Global Impressions Improvement score >=6 or a psychiatric
      rehospitalization. RESULTS: All patients were treated with neuroleptic medication
      after the acute ECT course. The relapse-free rate of all 43 patients at 1 year
      was 57.3%, and the median relapse-free period was 21.5 months. Multivariate
      analysis showed that the number of ECT sessions was associated with a significant
      increase in the risk of relapse (hazard ratio: 1.159; P=0.033). Patients who were
      treated with adjunctive mood stabilizers as maintenance pharmacotherapy after the
      response to the acute ECT course were at a lower risk of relapse than were those
      treated without mood stabilizers (hazard ratio: 0.257; P=0.047). CONCLUSION: Our
      study on the recurrence of schizophrenia after a response to an acute ECT course
      suggests that the number of ECT sessions might be related to the risk of relapse
      and that adjunctive mood stabilizers might be effective in preventing relapse.

PMID- 25609969
TI  - The impact of internalizing symptoms on autistic traits in adolescents with
      restrictive anorexia nervosa.
AB  - BACKGROUND: Although previous studies indicated a positive association between
      restrictive anorexia-nervosa (AN-R) and autistic traits, the potential
      interference of psychiatric internalizing comorbidity on this association is not
      yet fully investigated. MATERIALS AND METHODS: The aim of this study was to
      explore autistic traits and internalizing psychopathology in adolescents (age
      range: 11.7-17.2 years) with AN-R. Twenty-five patients referred to two tertiary
      care hospitals were compared to a large control group (N=170) with no differences
      in age and sex. AN-R patients and controls filled out instruments assessing
      autistic traits (autism spectrum quotient [AQ]), psychopathology (youth self
      report [YSR] 11-18), and eating patterns (eating attitude test [EAT]). In order
      to disentangle the possible mediating role of internalizing symptoms on autistic
      traits, two separate control groups (called True and False healthy control, both
      composed of 25 eating-problem-free participants) were derived from the whole
      control group on the basis of the presence or absence of internalizing problems
      in the YSR. RESULTS: AN-R patients scored significantly higher on AQ compared to
      the whole control group and to controls without internalizing problems (True HC),
      but these differences disappeared when only controls with internalizing problems
      (False HC) were considered. CONCLUSION: Autistic traits in AN-R individuals may
      have been overestimated and may partly be due to comorbid internalizing symptoms
      in investigated patients.

PMID- 25609970
TI  - The role of family therapy in the management of schizophrenia: challenges and
      solutions.
AB  - Family interventions for schizophrenia have been amply demonstrated to be
      effective and are recommended by most of the international clinical guidelines.
      However, their implementation in the clinical setting as well as in treatment
      protocols of patients with psychosis has not been fully achieved yet. With the
      increasing deinstitutionalization of patients, family has begun to assume the
      role of care performed by psychiatric hospitals, with a high emotional cost for
      caregivers as well as the recognition of burden experiences. Families have been
      the substitute in the face of the scarcity of therapeutic, occupational, and
      residential resources. For this reason, the viability of patients' care by their
      families has become a challenge. This article aims to discuss the most important
      aspects of family interventions, their impact on families, and the most important
      challenges that need to be overcome in order to achieve well-being and recovery
      in both patients and caregivers. 

PMID- 25609971
TI  - Fish oil supplementation associated with decreased cellular degeneration and
      increased cellular proliferation 6 weeks after middle cerebral artery occlusion
      in the rat.
AB  - Anti-inflammatory long-chain omega-3 polyunsaturated fatty acids (n-3-LC-PUFAs)
      are both neuroprotective and have antidepressive effects. However the influence
      of dietary supplemented n-3-LC-PUFAs on inflammation-related cell death and
      proliferation after middle cerebral artery occlusion (MCAo)-induced stroke is
      unknown. We have previously demonstrated that anxiety-like and hyperactive
      locomotor behaviors are reduced in n-3-LC-PUFA-fed MCAo animals. Thus in the
      present study, male hooded Wistar rats were exposed to MCAo or sham surgeries and
      examined behaviorally 6 weeks later, prior to euthanasia and examination of
      lesion size, cell death and proliferation in the dentate gyrus, cornu ammonis
      region of the hippocampus of the ipsilesional hemispheres, and the thalamus of
      the ipsilesional and contralesional hemispheres. Markers of cell genesis and cell
      degeneration in the hippocampus or thalamus of the ipsilesional hemisphere did
      not differ between surgery and diet groups 6 weeks post MCAo. Dietary
      supplementation with n-3-LC-PUFA decreased cell degeneration and increased cell
      proliferation in the thalamic region of the contralesional hemisphere. MCAo
      associated cell degeneration in the hippocampus and thalamus positively
      correlated with anxiety-like and hyperactive locomotor behaviors previously
      reported in these animals. These results suggest that anti-inflammatory n-3-LC
      PUFA supplementation appears to have cellular protective effects after MCAo in
      the rat, which may affect behavioral outcomes. 

PMID- 25609972
TI  - Biologics in the management of ulcerative colitis - comparative safety and
      efficacy of TNF-alpha antagonists.
AB  - Ulcerative colitis can cause debilitating symptoms and complications such as
      colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or
      perforation. Goals of treatment in ulcerative colitis include resolution of
      gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease
      complications. Our treatment armamentarium has expanded dramatically over the
      past 10 years, and we now have multiple biologic agents approved for the
      treatment of moderate-severe disease, in addition to conventional therapies such
      as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will
      provide a detailed discussion of the three tumor necrosis factor-alpha (TNF
      alpha) inhibitors currently approved for treatment of ulcerative colitis:
      infliximab, adalimumab, and golimumab. All three agents are effective for
      inducing and maintaining clinical response and remission in patients with
      ulcerative colitis, and they have comparable safety profiles. There are no head
      to-head trials comparing their efficacy, and the choice of agent is most often
      based on insurance coverage, route of administration, and patient preference.
      Combination therapy with an immunomodulator is proven to be more effective than
      anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should
      undergo dose intensification in order to regain clinical response. Despite
      therapeutic optimization, a significant percentage of patients will not achieve
      clinical remission with anti-TNF agents, and so newer therapies are on the
      horizon. 

PMID- 25609973
TI  - Management of bipolar I depression: clinical utility of lurasidone.
AB  - Lurasidone is a benzisothiazol derivative second-generation antipsychotic. It has
      been approved in the United States and Europe for treatment of acute
      schizophrenia and bipolar depression. In type I bipolar subjects, treatment with
      lurasidone monotherapy of adjunctive therapy to lithium or valproic acid with
      doses of 20 to 120 mg once daily with food, results in statistically and
      clinically significant reduction of depressive symptoms. Patients experience
      relatively few side effects, which include somnolence, akathisia, nausea, and
      other gastrointestinal upset. Dopamine related side effects, such as Parkinsonism
      and elevated prolactin, are rare and mild. Longer term safety data obtained in 6
      months long, open continuation observation periods, suggest that metabolic
      related elevations in weight, glucose, and lipids are absent or minimal. The
      mechanism of action of lurasidone is not known, but the data are compatible with
      antagonism of the serotonin 7 receptor. Lurasidone is a new option for the
      treatment of bipolar depression with relatively few side effects. 

PMID- 25609974
TI  - Tapentadol extended release in the management of peripheral diabetic neuropathic
      pain.
AB  - Tapentadol, a MU-opioid agonist and norepinephrine reuptake inhibitor, has been
      found to be an effective medication for a wide variety of chronic pain
      conditions, including back pain, cancer-related pain, and arthritic pain. It has
      also been found to have fewer gastrointestinal side effects than more traditional
      opioid-based therapies. More recently, tapentadol extended release has been
      demonstrated to be effective in the management of painful diabetic neuropathy, an
      often debilitating condition affecting approximately one-third of all patients
      with diabetes. This review highlights the most up-to-date basic and clinical
      studies by focusing on the mechanisms of action of tapentadol and its clinical
      efficacy, especially with regard to painful diabetic neuropathy. 

PMID- 25609976
TI  - A comparison of effectiveness of hepatitis B screening and linkage to care among
      foreign-born populations in clinical and nonclinical settings.
AB  - Hepatitis B (HBV) is an urgent, unmet public health issue that affects Asian
      Americans disproportionately. Of the estimated 1.2 million living with chronic
      hepatitis B in USA, more than 50% are of Asian ethnicity, despite the fact that
      Asian Americans constitute less than 6% of the total US population. The Centers
      for Disease Control and Prevention recommends HBV screening of persons who are at
      high risk for the disease. Yet, large numbers of Asian Americans have not been
      diagnosed or tested, in large part because of perceived cultural and linguistic
      barriers. Primary care physicians are at the front line of the US health care
      system, and are in a position to identify individuals and families at risk.
      Clinical settings integrated into Asian American communities, where physicians
      are on staff and wellness care is emphasized, can provide testing for HBV. In
      this study, the Asian Health Coalition and its community partners conducted HBV
      screenings and follow-up linkage to care in both clinical and nonclinical
      settings. The nonclinic settings included health fair events organized by
      churches and social services agencies, and were able to reach large numbers of
      individuals. Twice as many Asian Americans were screened in nonclinical settings
      than in health clinics. Chi-square and independent samples t-test showed that
      participants from the two settings did not differ in test positivity, sex,
      insurance status, years of residence in USA, or education. Additionally, the same
      proportion of individuals found to be infected in the two groups underwent
      successful linkage to care. Nonclinical settings were as effective as clinical
      settings in screening for HBV, as well as in making treatment options available
      to those who tested positive; demographic factors did not confound the
      similarities. Further research is needed to evaluate if linkage to care can be
      accomplished equally efficiently on a larger scale. 

PMID- 25609977
TI  - Physicians' experience adopting the electronic transfer of care communication
      tool: barriers and opportunities.
AB  - PURPOSE: The purpose of this study was to assess physicians' perceptions on a
      newly developed electronic transfer of care (e-TOC) communication tool and
      identify barriers and opportunities toward its adoption. PARTICIPANTS AND
      METHODS: The study was conducted in a tertiary care teaching center as part of a
      randomized controlled trial assessing the efficacy of an e-TOC communication
      tool. The e-TOC technology was developed through iterative consultation with
      stakeholders. This e-TOC summary was populated by acute care physicians (AcPs)
      and communicated electronically to community care physicians (CcPs). The AcPs
      consisted of attending physicians, resident trainees, and medical students
      rotating through the Medical Teaching Unit. The CcPs were health care providers
      caring for patients discharged from hospital to the community. AcPs and CcPs
      completed validated surveys assessing their experience with the newly developed e
      TOC tool. Free text questions were added to gather general comments from both
      groups of physicians. Units of analysis were individual physicians. Data from the
      surveys were analyzed using mixed methods. RESULTS: AcPs completed 138 linked pre
      and post-rotation surveys. At post-rotation, each AcP completed an average of
      six e-TOC summaries, taking an average of 37 minutes per e-TOC summary. Over 100
      CcPs assessed the quality of the TOC summaries, with an overall rating of 8.3
      (standard deviation: 1.48; on a scale of 1-10). Thematic analyses revealed
      barriers and opportunities encountered by physicians toward the adoption of the e
      TOC tool. While the AcPs highlighted issues with timeliness, usability, and
      presentation, the CcPs identified barriers accessing the web-based TOC summaries,
      emphasizing that the summaries were timely and the quality of information
      supported continuity of care. CONCLUSION: Despite the barriers identified by both
      groups of physicians, the e-TOC communication tool was well received. Our
      experience can serve as a template for other health research teams considering
      the implementation of e-health technologies into health care systems.

PMID- 25609978
TI  - Structured nursing communication on interdisciplinary acute care teams improves
      perceptions of safety, efficiency, understanding of care plan and teamwork as
      well as job satisfaction.
AB  - Efficient, accurate, and timely communication is required for quality health care
      and is strongly linked to health care staff job satisfaction. Developing ways to
      improve communication is key to increasing quality of care, and interdisciplinary
      care teams allow for improved communication among health care professionals. This
      study examines the patient- and family-centered use of structured
      interdisciplinary bedside rounds (SIBR) on an acute care for the elderly (ACE)
      unit in a 555-bed metropolitan community hospital. This mixed methods study
      surveyed 24 nurses, therapists, patient care assistants, and social workers to
      measure perceptions of teamwork, communication, understanding of the plan for the
      day, safety, efficiency, and job satisfaction. A similar survey was administered
      to a control group of 38 of the same staff categories on different units in the
      same hospital. The control group units utilized traditional physician-centric
      rounding. Significant differences were found in each category between the SIBR
      staff on the ACE unit and the control staff. Nurse job satisfaction is an
      important marker of retention and recruitment, and improved communication may be
      an important aspect of increasing this satisfaction. Furthermore, improved
      communication is key to maintaining a safe hospital environment with quality
      patient care. Interdisciplinary team rounds that take place at the bedside
      improve both nursing satisfaction and related communication markers of quality
      and safety, and may help to achieve higher nurse retention and safer patient
      care. These results point to the interconnectedness and dual benefit to both job
      satisfaction and patient quality of care that can come from enhancements to team
      communication. 

PMID- 25609975
TI  - Influence of immune activation and inflammatory response on cardiovascular risk
      associated with the human immunodeficiency virus.
AB  - Patients infected with the human immunodeficiency virus (HIV) have an increased
      cardiovascular risk. Although initially this increased risk was attributed to
      metabolic alterations associated with antiretroviral treatment, in recent years,
      the attention has been focused on the HIV disease itself. Inflammation, immune
      system activation, and endothelial dysfunction facilitated by HIV infection have
      been identified as key factors in the development and progression of
      atherosclerosis. In this review, we describe the epidemiology and pathogenesis of
      cardiovascular disease in patients with HIV infection and summarize the latest
      knowledge on the relationship between traditional and novel inflammatory, immune
      activation, and endothelial dysfunction biomarkers on the cardiovascular risk
      associated with HIV infection. 

PMID- 25609979
TI  - Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes
      among Indian patients with adenocarcinoma of the lung.
AB  - BACKGROUND: Mutation in the tyrosine kinase domain of epidermal growth factor
      receptor (EGFR) is a common feature observed in lung adenocarcinoma. A fusion
      gene between echinoderm microtubule-associated protein-like 4 (EML4) and the
      intracellular domain of anaplastic lymphoma kinase (ALK), named EML4-ALK, has
      been identified in a subset of non-small-cell lung cancer (NSCLC) tumors. The
      objective of this study was to determine the prevalence of EGFR mutations and
      EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as
      evaluate their clinical characteristics. PATIENTS AND METHODS: Patients with
      NSCLC, adenocarcinoma histology, whose tumors had been tested for EGFR mutational
      status, were considered for this study. ALK gene rearrangement was detected by
      fluorescence in situ hybridization using the Vysis ALK Break Apart Rearrangement
      Probe Kit. ALK mutation was tested in samples that were negative for EGFR
      mutation. RESULTS: A total of 500 NSCLC adenocarcinoma patients were enrolled
      across six centers. There were 337 (67.4%) men and 163 (32.6%) women with a
      median age of 58 years. One hundred and sixty-four (32.8%) blocks were positive
      for EGFR mutations, whereas 336 (67.2%) were EGFR wild-type. Of the 336 EGFR
      negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas
      321 (95.5%) tumors were EML4-ALK negative. The overall incidence of EML4-ALK
      fusion gene was 3% (15/500). CONCLUSION: The incidence of EGFR mutations (33%) in
      this Indian population is close to the reported incidence in Asian patients. EML4
      ALK gene fusions are present in lung adenocarcinomas from Indian patients, and
      the 3% incidence of EML4-ALK gene fusion in EGFR mutation-negative cases is
      similar to what has been observed in other Western and Asian populations. The
      mutual exclusivity of EML4-ALK and EGFR mutations suggests implementation of
      biomarker testing for tumors harboring ALK rearrangements in order to identify
      patients that can benefit from newer targeted therapies.

PMID- 25609981
TI  - Low preoperative lymphocyte to monocyte ratio predicts poor cancer-specific
      survival in patients with esophageal squamous cell carcinoma.
AB  - BACKGROUND: Recent studies have shown that the lymphocyte to monocyte ratio (LMR)
      is a useful predictive factor in various cancers. However, the prognostic value
      of LMR in patients with esophageal cancer has not been reported yet. The purpose
      of the current study was to determine the prognostic role of LMR in esophageal
      squamous cell carcinoma (ESCC). METHODS: Three-hundred and forty-eight patients
      who had undergone esophagectomy for ESCC were included. A receiver operating
      characteristic curve for survival prediction was plotted to verify the optimum
      cut-off point for LMR. Kaplan-Meier method was used to calculate the cancer
      specific survival (CSS), the difference was assessed by the log-rank test.
      Univariate and multivariate analyses were performed to evaluate the prognostic
      factors. RESULTS: A receiver operating characteristic curve for survival
      prediction was plotted to verify the optimum cut-off point for LMR, which was
      2.93. Patients with LMR <=2.93 had a significantly worse 5-year CSS than patients
      with LMR >2.93 (21.2% versus 59.3%, P<0.001). For subgroup analysis, the
      predictive value of LMR was also significant in patients with T1-2 cancer
      (P=0.003), T3-4a (P<0.001), and patients with (P=0.044) or without (P<0.001)
      nodal metastasis. In addition, the predictive value of LMR was also significant
      stratified by absolute lymphocyte count (P<0.001) and absolute monocyte count
      (P<0.001). In multivariate analysis, LMR was a significant predictive factor of
      CSS (P=0.010). CONCLUSION: LMR is still a predictive factor for long-term
      survival in patients with ESCC. We conclude that 2.93 may be the optimum cut-off
      point for LMR in predicting survival in ESCC patients.

PMID- 25609982
TI  - Prognostic role of apoptosis-related gene functional variants in advanced non
      small-cell lung cancer patients treated with first-line platinum-based
      chemotherapy.
AB  - BACKGROUND: Single-nucleotide polymorphisms in apoptosis-related genes have been
      shown to play a role in the efficacy of platinum-based chemotherapy and may
      influence clinical outcomes. Our study aimed to evaluate the correlations of four
      functional single-nucleotide polymorphisms - FAS -670 A>G, FAS ligand -844 T>C,
      survivin -31 G>C, and survivin 9386 C>T - with drug response and clinical
      outcomes in advanced non-small-cell lung cancer patients who received platinum
      based chemotherapy. MATERIALS AND METHODS: Polymorphisms were evaluated using the
      polymerase chain reaction-based restriction fragment-length polymorphism
      technique. RESULTS: Patients with the CC genotype of FAS -670 A>G had worse
      overall survival (OS) than those with the CT or TT genotype (P=0.044), with
      median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively.
      Furthermore, progression-free survival was associated with the FAS -670 A>G
      polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of
      survivin 9386 C>T experienced improved survival compared with patients with the
      TT genotype (median OS 31.4 months and 22.8 months, respectively). CONCLUSION:
      The functional FAS -670 A>G and survivin 9386 C>T polymorphisms are potential
      independent prognostic factors in advanced non-small-cell lung cancer patients
      treated with platinum-based chemotherapy.

PMID- 25609980
TI  - Advances in the targeted therapy of liposarcoma.
AB  - Liposarcoma (LPS) is the most common type of soft-tissue sarcoma. Complete
      surgical resection is the only curative means for localized disease; however,
      both radiation and conventional cytotoxic chemotherapy remain controversial for
      metastatic or unresectable disease. An increasing number of trials with novel
      targeted therapy of LPS have provided encouraging data during recent years. This
      review will provide an overview of the advances in our understanding of LPS and
      summarize the results of recent trials with novel therapies targeting different
      genetic and molecular aberrations for different subtypes of LPS. 

PMID- 25609984
TI  - Failure of Y-27632 to improve the culture of adult human adipose-derived stem
      cells.
AB  - Y-27632 is a well-known inhibitor of the Rho-associated coiled kinase (ROCK) and
      has been shown to significantly improve the culture of a variety of multipotent
      stem cell types. However, the effects of Y-27632 on the expansion of adult human
      adipose-derived stem cell (hADSC) cultures remain to be established. Here, we
      aimed to characterize the effects of Y-27632 on the culture of hADSCs. Adult
      hADSCs were isolated from subjects submitted to elective plastic surgery
      procedures and cultivated in vitro under optimized conditions. Our results show
      that the continuous supplementation of hADSC cultures with Y-27632 led to
      decreased numbers of cells and decreased global metabolic viability of hADSC
      cultures when compared with control conditions. This effect appeared to be
      dependent on the continuous presence of the drug and was shown to be
      concentration-dependent and significant for 10 MUM and 20 MUM of Y-27632.
      Moreover, the Y-27632-induced decrease in hADSC numbers was not linked to a block
      in global cell proliferation, as cell numbers consistently increased from the
      moment of plating until passaging. In addition, Y-27632 was not able to increase
      the number of hADSCs present in culture 24 hours after passaging. Taken together,
      our results suggest that, in contrast to other stem cell types, Y-27632
      supplementation is not a suitable strategy to enhance hADSC culture expansion. 

PMID- 25609983
TI  - Identification of highly conserved regions in L-segment of Crimean-Congo
      hemorrhagic fever virus and immunoinformatic prediction about potential novel
      vaccine.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease
      with a disease fatality rate between 15% and 70%. Despite the wide range of
      distribution, the virus (CCHFV) is basically endemic in Africa, Asia, eastern
      Europe, and the Middle East. Acute febrile illness associated with petechiae,
      disseminated intravascular coagulation, and multiple-organ failure are the main
      symptoms of the disease. With all these fatal effects, CCHFV is considered a huge
      threat as no successful therapeutic approach is currently available for the
      treatment of this disease. In the present study, we have used the
      immunoinformatics approach to design a potential epitope-based vaccine against
      the RNA-dependent RNA polymerase-L of CCHFV. Both the T-cell and B-cell epitopes
      were assessed, and the epitope "DCSSTPPDR" was found to be the most potential
      one, with 100% conservancy among all the strains of CCHFV. The epitope was also
      found to interact with both type I and II major histocompatibility complex
      molecules and is considered nonallergenic as well. In vivo study of our proposed
      peptide is advised for novel universal vaccine production, which might be an
      effective path to prevent CCHF disease. 

PMID- 25609985
TI  - Long-acting muscarinic antagonist use in adults with asthma: real-life
      prescribing and outcomes of add-on therapy with tiotropium bromide.
AB  - BACKGROUND: Randomized controlled trials indicate that addition of a long-acting
      muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and
      reduce exacerbation risk in patients with poorly controlled asthma, but broader
      clinical studies are needed to investigate the effectiveness of LAMA in real-life
      asthma care. METHODS: Medical records of adults with asthma (aged >=18 years)
      prescribed tiotropium were obtained from the UK Optimum Patient Care Research
      Database for the period 2001-2013. Patients diagnosed with chronic obstructive
      pulmonary disease were excluded, but no other clinical exclusions were applied.
      Two primary outcomes were compared in the year before (baseline) and the year
      after (outcome) addition of tiotropium: exacerbations (asthma-related hospital
      emergency department attendance or inpatient admission, or acute oral
      corticosteroid course) and acute respiratory events (exacerbation or antibiotic
      prescription with lower respiratory consultation). Secondary outcomes included
      lung function test results and short-acting beta2 agonist usage. The Wilcoxon
      signed-rank test was used for variables measured on the interval scale, the
      marginal homogeneity test for categorized variables, and the paired t-test for
      lung function indices. RESULTS: Of the 2,042 study patients, 83% were prescribed
      an inhaled corticosteroid and 68% a long-acting beta2 agonist during the baseline
      year; 67% were prescribed both. Comparing baseline and outcome years, the
      percentage of patients having at least one exacerbation decreased from 37% to 27%
      (P<0.001) and the percentage having at least one acute respiratory event
      decreased from 58% to 47% (P<0.001). There were no significant changes in lung
      function, and usage of short-acting beta2 agonists (in salbutamol/albuterol
      equivalents) increased from a median (interquartile range) of 274 (110, 548) to
      329 (110, 603) MUg/day (P=0.01). CONCLUSION: In this real-life asthma population,
      addition of LAMA therapy was associated with significant decreases in the
      incidence of exacerbations and antibiotic prescriptions for lower respiratory
      tract infections in the following year.

PMID- 25609986
TI  - Assessing the importance of predictors in unplanned hospital readmissions for
      chronic obstructive pulmonary disease.
AB  - PURPOSE: The all-cause readmission rate within 30 days of index admissions for
      chronic obstructive pulmonary disease (COPD) was approximately 21% in the United
      States in 2008. This study aimed to examine patient and clinical characteristics
      predicting 30-day unplanned readmissions for an initial COPD hospitalization and
      to determine those predictors' importance. PATIENTS AND METHODS: A retrospective
      study was conducted in patients with COPD-related hospitalizations using
      commercial claims data from 2010 to 2012. The primary outcome was all-cause
      unplanned readmission, with secondary outcomes being COPD as primary diagnosis
      and COPD as any diagnosis unplanned readmissions. Factors predicting unplanned
      readmissions encompassed demographic, pharmacy, and medical variables identified
      at baseline and during the index hospitalization. Dominance analysis was
      conducted to rank the predictors in terms of importance, defined as the
      contribution to change in model fit of a predictor by itself and in combination
      with other predictors. RESULTS: After applying the inclusion and exclusion
      criteria, 18,282 patients with index COPD-related admissions were identified.
      Among them, the rates of unplanned readmissions with COPD as primary diagnosis,
      COPD as any diagnosis, and all-cause were 2.6%, 5.6%, and 7.3%, respectively. For
      each outcome, the readmission group was slightly older, had a greater COPD
      severity score, and required a longer length of stay. Moreover, the readmission
      group had larger proportions of patients with comorbidities, dyspnea/shortness of
      breath, intensive care unit stay, or ventilator use, compared to the non
      readmission group. Dominance analysis revealed that the three most important
      predictors - heart failure/heart disease, anemia, and COPD severity score -
      accounted for 56% of the predicted variance in all-cause unplanned readmissions.
      CONCLUSION: Overall, COPD severity score and heart failure/heart disease emerged
      as important factors in predicting 30-day unplanned readmissions across all three
      outcomes. Results from dominance analysis suggest looking beyond COPD-specific
      complications and focusing on comorbid conditions highly associated with COPD in
      order to lower all-cause unplanned readmissions.

PMID- 25609987
TI  - End-stage renal disease in autosomal dominant polycystic kidney disease: a
      comparison of dialysis-related utilization and costs with other chronic kidney
      diseases.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the leading
      inheritable cause of end-stage renal disease (ESRD) and one of the leading causes
      of ESRD overall. ADPKD patients differ from the overall dialysis population;
      however, there is little published data regarding health care costs for ADPKD
      patients on dialysis. METHODS: This retrospective observational cohort study was
      designed to quantify health care utilization and costs for ADPKD patients with
      ESRD who received initial services at a single large dialysis organization
      between January 1, 2007 and December 31, 2009. Parallel results and baseline
      patient characteristics for control patients with ESRD etiologies other than
      ADPKD were performed for reference. Dialysis-related utilization and health care
      costs for patients with ADPKD in ESRD overall and during time horizons that
      correspond to Medicare-eligibility benchmarks were analyzed. Baseline patient
      characteristics were described for all patients and included demographics,
      comorbid illnesses, and clinical characteristics. Dialysis-related utilization,
      hospitalization rates, and health care costs were considered longitudinally.
      RESULTS: Total health care costs for ADPKD patients were high at US$51,048 per
      patient-year based on the overall analysis. Total health care costs were lower
      for ADPKD patients than for control patients on dialysis. Patients with ADPKD
      were generally younger, had a lower Charlson Comorbidity Index, and had lower
      rates of comorbid conditions, which may have contributed to the lower overall
      costs seen for patients with ADPKD. CONCLUSION: Health care resource utilization
      and costs for patients with ADPKD in ESRD requiring dialysis were high, and
      therapeutic interventions that can prevent or delay the progression to ESRD may
      increase dialysis-free life for patients with ADPKD.

PMID- 25609989
TI  - Type 2 diabetes in Brazil: epidemiology and management.
AB  - Type 2 diabetes mellitus (T2DM) is one of the most important epidemic diseases in
      the world this century, and accounts for 90% of cases of diabetes globally.
      Brazil is one of the most important examples of the alarming picture of T2DM in
      emergent societies, being the country with the fourth largest number of people
      with diabetes. The aim of this paper is to review the literature on diabetes in
      Brazil, specifically looking at the epidemiology and management of T2DM. A
      literature search was conducted using PubMed and LILACS to identify articles
      containing information on diabetes in Brazil. Official documents from the
      Brazilian government, World Health Organization, and International Diabetes
      Federation were also reviewed. 

PMID- 25609988
TI  - Annual biologic treatment cost for new and existing patients with moderate to
      severe plaque psoriasis in Greece.
AB  - AIM: The aim of the present study was to estimate the annual per-patient cost of
      treatment with adalimumab, etanercept, infliximab, and ustekinumab by response
      status for new and existing patients with moderate to severe psoriasis in Greece.
      METHODS: An economic analysis was developed from a national health care
      perspective to estimate the direct cost of treatment alternatives for new and
      existing patients within a 1-year time horizon. The model included drug
      acquisition and administration costs for responders and nonresponders. Real-world
      treatment pattern and resource use data were extracted through nationwide field
      research using telephone-based interviews with a representative sample of
      dermatologists. Unit costs were collected from official sources in the public
      domain. RESULTS: The mean annual cost of treatment for new patients who responded
      (or did not respond) to treatment was as follows: adalimumab ?10,686 (?3,821),
      etanercept ?10,415 (?3,224), infliximab ?14,738 (?7,582), and ustekinumab ?17,155
      (?9,806). For existing patients the mean annual cost was ?9,916, ?9,462, ?12,949,
      and ?17,149, respectively. Results did not change significantly under several one
      way sensitivity and scenario analyses. CONCLUSION: Under the base-case scenario,
      the cost of treatment with etanercept is lower than that of the other biological
      agents licensed for moderate to severe plaque psoriasis in Greece, for both new
      and existing patients, irrespective of response status.

PMID- 25609990
TI  - Glycemic control after initiating basal insulin therapy in patients with type 2
      diabetes: a primary care database analysis.
AB  - BACKGROUND: When target glycated hemoglobin (HbA1c) levels are not reached, basal
      insulin therapy should be considered in type 2 diabetes. The objective of this
      report was to describe the predictors of glycemic control (strict criterion:
      HbA1c <=6.5%) during the first year after initiating basal insulin therapy in
      primary care. METHODS: The study applied a retrospective approach using a
      nationwide database in Germany (Disease Analyzer, IMS Health, January 2008 to
      December 2011, including 1,024 general and internal medicine practices).
      Potential predictors of glycemic control considered were age, sex, duration of
      diabetes, type of basal insulin, comedication with short-acting insulin, baseline
      HbA1c, previous oral antidiabetic drugs, diabetologist care, private health
      insurance, macrovascular and microvascular comorbidity, and concomitant
      medication. Multivariable logistic regression models were fitted with glycemic
      control as the dependent variable. RESULTS: A total of 4,062 type 2 diabetes
      patients started basal insulin (mean age 66 years, males 53%, diabetes duration
      4.8 years, mean HbA1c 8.8%), of whom 295 (7.2%) achieved an HbA1c <=6.5% during
      the one-year follow-up. Factors positively associated with HbA1c <=6.5% in
      logistic regression were male sex (odds ratio 1.59, 95% confidence interval 1.23
      2.04), insulin glargine (reference neutral protamine Hagedorn; odds ratio 1.43,
      95% confidence interval 1.09-1.88), short-acting insulin (odds ratio 1.33, 95%
      confidence interval 1.01-1.76), and prior treatment with metformin, dipeptidyl
      peptidase-4 inhibitors, and diuretics. Lipid-lowering drugs were associated with
      a lower odds of reaching the glycemic target. CONCLUSION: Few type 2 diabetes
      patients (7%) reached the glycemic target (HbA1c <=6.5%) after one year of basal
      insulin therapy. Achievement of the glycemic target was associated with type of
      basal insulin, additional short-acting insulins, previous antidiabetic
      medication, and other comedication, eg, diuretics or lipid-lowering drugs.

PMID- 25609991
TI  - An extract of the medicinal plant Artemisia annua modulates production of
      inflammatory markers in activated neutrophils.
AB  - PURPOSE: To investigate the ability of a commercial extract from the medicinal
      plant Artemisia annua to modulate production of the cytokine, tumor necrosis
      factor-alpha (TNF-alpha), and the cyclooxygenase (COX) inflammatory marker,
      prostaglandin E2 (PGE2) in activated neutrophils. METHODS: Neutrophils were
      harvested from rat whole blood and cultured in the presence of plant extract or
      control samples. Neutrophils, except unactivated control cells, were activated
      with 10 MUg/mL lipopolysaccharide (LPS). The cells were cultured with a range of
      different concentrations of the A. annua extracts (400-1 MUg/mL) and artemisinin
      (200 and 100 MUg/mL) and the supernatants were then tested by enzyme-linked
      immunosorbent assay (ELISA) for the concentrations of TNF-alpha and PGE2. Each
      sample was assayed in triplicate. Positive controls with an inhibitor were
      assayed in triplicate: chloroquine 2.58 and 5.16 MUg/mL for TNF-alpha, and
      ibuprofen 400 MUg/mL for PGE2. An unsupplemented group was also assessed in
      triplicate as a baseline control. RESULTS: Neutrophils were stimulated to an
      inflammatory state by the addition of LPS. A. annua extract significantly
      inhibited TNF-alpha production by activated neutrophils in a dose-dependent
      manner. There was complete inhibition by the A. annua extract at 200, 100, and 50
      MUg/mL (all P<=0.0003). At A. annua extract concentrations of 25, 10, and 5
      MUg/mL, TNF-alpha production was inhibited by 89% (P<0.0001), 54% (P=0.0002), and
      38% (P=0.0014), respectively. A. annua 1 MUg/mL did not significantly inhibit TNF
      alpha production (8.8%; P>0.05). Concentrations of 400, 200, and 100 MUg/mL A.
      annua extract significantly inhibited PGE2 production by 87% (P=0.0128), 91%
      (P=0.0017), and 93% (P=0.0114), respectively. CONCLUSION: An extract of A. annua
      was shown to be a potent inhibitor of TNF-alpha and a strong inhibitor of PGE2
      production in activated neutrophils at the concentrations tested. Further studies
      are warranted with this promising plant extract.

PMID- 25609992
TI  - Genomic-based tools for the risk assessment, management, and prevention of type 2
      diabetes.
AB  - Type 2 diabetes (T2D) is a common and serious disorder and is a significant risk
      factor for the development of cardiovascular disease, neuropathy, nephropathy,
      retinopathy, periodontal disease, and foot ulcers and amputations. The burden of
      disease associated with T2D has led to an emphasis on early identification of the
      millions of individuals at high risk so that management and intervention
      strategies can be effectively implemented before disease progression begins. With
      increasing knowledge about the genetic basis of T2D, several genomic-based
      strategies have been tested for their ability to improve risk assessment,
      management and prevention. Genetic risk scores have been developed with the
      intent to more accurately identify those at risk for T2D and to potentially
      improve motivation and adherence to lifestyle modification programs. In addition,
      evidence is building that oral antihyperglycemic medications are subject to
      pharmacogenomic variation in a substantial number of patients, suggesting
      genomics may soon play a role in determining the most effective therapies. T2D is
      a complex disease that affects individuals differently, and risk prediction and
      treatment may be challenging for health care providers. Genomic approaches hold
      promise for their potential to improve risk prediction and tailor management for
      individual patients and to contribute to better health outcomes for those with
      T2D. 

PMID- 25609993
TI  - The genetics of Meniere's disease.
AB  - Our understanding of the genetic basis of Meniere's disease (MD) is still
      limited. Although the familial clustering and the geographical and racial
      differences in incidence strongly suggest a certain role for genetic factors in
      the development of MD, no convincing evidence for an association with any gene
      exists, at present. In this review, starting from rational bases for a genetic
      approach to MD, we explored the numerous reports published in literature and
      summarize the recent advances in understanding of the genetic fundaments of the
      disease. 

PMID- 25609994
TI  - Systemic inflammatory response syndrome and platelet count >=250*10(9) are
      associated with venous thromboembolic disease.
AB  - INTRODUCTION: Prior research has demonstrated that platelet count and
      inflammation are dominant contributors to hypercoagulability. Our objective is to
      determine whether elevated platelet count and systemic inflammatory response
      syndrome (SIRS) have an association with the development of venous
      thromboembolism (VTE) in hospitalized patients with a high clinical index of
      suspicion for thromboembolic disease. METHODS: We performed a retrospective
      medical record review of 844 medical and surgical patients with suspected VTE
      hospitalized from July 2012 to May 2013 who underwent screening by venous duplex
      and computed tomography pulmonary angiogram. For our purposes, thrombocytosis was
      arbitrarily defined as platelet count >=250*10(9)/L. RESULTS: Venous
      thromboembolic disease was detected in 229 patients (25.9%). Thrombocytosis was
      present in 389 patients (44%) and SIRS was present in 203 patients (23%) around
      the time of imaging. Thrombocytosis and SIRS were positively correlated with VTE
      (P<0.001). There was no correlation between thrombocytosis and SIRS. Multivariate
      analysis revealed that SIRS (odds ratio 1.91, 95% confidence interval 1.36-2.68,
      P<0.001) and thrombocytosis (odds ration 1.67, 95% confidence interval 1.23-2.26,
      P=0.001) were independently associated with VTE. CONCLUSION: Patients at high
      risk for VTE should be routinely assessed for thrombocytosis (>=250*10(9)/L) and
      SIRS; if either is present, consideration for empiric anticoagulation should be
      given while diagnostic imaging is undertaken.

PMID- 25609996
TI  - The quest for effective pain control during suture adjustment after strabismus
      surgery: a study evaluating supplementation of 2% lidocaine with 0.4%
      ropivacaine.
AB  - PURPOSE: To determine whether the addition of 0.4% ropivacaine to the standard 2%
      lidocaine peribulbar anesthetic block improves pain scores during suture
      adjustment in patients undergoing strabismus surgery with adjustable sutures.
      METHODS: Prospective, double-blind study of 30 adult patients aged 21-84 years
      scheduled for elective strabismus surgery with adjustable sutures. Patients were
      divided into two groups of 15 patients each based on the local anesthetic. Group
      A received 2% lidocaine and Group B received 2% lidocaine/0.4% ropivacaine. Pain
      was assessed using the visual analog scale (VAS) preoperatively and at 2, 4, and
      6 hours postoperatively. The Lancaster red-green test was used to measure ocular
      motility at the same time points. RESULTS: The pain scores in the two groups were
      low and similar at all measurement intervals. The VAS for Group A versus Group B
      at 2 hours (1.7 versus 2.4, P=0.5) and 4 hours (3.5 versus 3.7, P=0.8) showed no
      benefit from the addition of ropivacaine. At 6 hours, the VAS (3.7 versus 2.7)
      was not statistically significant, but the 95% confidence interval indicated that
      ropivacaine may provide some benefit. A repeated measures ANOVA did not find a
      statistically significant difference in VAS scores over time (P=0.9). In
      addition, the duration of akinesia was comparable in both groups (P=0.7).
      CONCLUSION: We conclude that the 50:50 mixture of 2% lidocaine with 0.4%
      ropivacaine as compared to 2% lidocaine in peribulbar anesthetic blocks in
      adjustable-suture strabismus surgery does not produce significant improvements in
      pain control during the postoperative and adjustment phases. In addition,
      ropivacaine did not impair return of full ocular motility at 6 hours, which is
      advantageous in adjustable-suture strabismus surgery.

PMID- 25609995
TI  - Pain catastrophizing as a risk factor for chronic pain after total knee
      arthroplasty: a systematic review.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is a common and costly surgical
      procedure. Despite high success rates, many TKA patients develop chronic pain in
      the months and years following surgery, constituting a public health burden. Pain
      catastrophizing is a construct that reflects anxious preoccupation with pain,
      inability to inhibit pain-related fears, amplification of the significance of
      pain vis-a-vis health implications, and a sense of helplessness regarding pain.
      Recent research suggests that it may be an important risk factor for untoward TKA
      outcomes. To clarify this impact, we systematically reviewed the literature to
      date on pain catastrophizing as a prospective predictor of chronic pain following
      TKA. METHODS: We searched MEDLINE, EMBASE, and PsycINFO databases to identify
      articles related to pain catastrophizing, TKA, risk models, and chronic pain. We
      reviewed titles and abstracts to identify original research articles that met our
      specified inclusion criteria. Included articles were then rated for
      methodological quality. including methodological quality. Due to heterogeneity in
      follow-up, analyses, and outcomes reported across studies, a quantitative meta
      analysis could not be performed. RESULTS: We identified six prospective
      longitudinal studies with small-to-mid-sized samples that met the inclusion
      criteria. Despite considerable variability in reported pain outcomes, pain
      catastrophizing was identified as a significant predictor of chronic pain
      persisting >=3 months following TKA in five of the studies assessed. Limitations
      of studies included lack of large-scale data, absence of standardized pain
      measurements, inadequate multivariate adjustment, such as failure to control for
      analgesic use and other relevant covariates, and failure to report non
      significant parameter estimates. CONCLUSION: This study provides moderate-level
      evidence for pain catastrophizing as an independent predictor of chronic pain
      post-TKA. Directions for future research include larger, well-controlled studies
      with standard pain outcomes, identification of clinically-relevant
      catastrophizing cut-offs that predict pain outcomes, investigation of other
      psychosocial risk factors, and assessment of interventions aimed to reduce pain
      catastrophizing on chronic pain outcomes following TKA surgery.

PMID- 25609997
TI  - Factors associated with contralateral preventive mastectomy.
AB  - INTRODUCTION: Contralateral prophylactic mastectomy (CPM) is an option for women
      who wish to reduce their risk of breast cancer or its local recurrence. There is
      limited data on demographic differences among patients who choose to undergo this
      procedure. METHODS: The population-based Florida cancer registry, Florida's
      Agency for Health Care Administration data, and US census data were linked and
      queried for patients diagnosed with invasive breast cancer from 1996 to 2009. The
      main outcome variable was the rate of CPM. Primary predictors were race,
      ethnicity, socioeconomic status (SES), marital status and insurance status.
      RESULTS: Our population was 91.1% White and 7.5% Black; 89.1% non-Hispanic and
      10.9% Hispanic. Out of 21,608 patients with a single unilateral invasive breast
      cancer lesion, 837 (3.9%) underwent CPM. Significantly more White than Black
      (3.9% vs 2.8%; P<0.001) and more Hispanic than non-Hispanic (4.5% vs 3.8%;
      P=0.0909) underwent CPM. Those in the highest SES category had higher rates of
      CPM compared to the lowest SES category (5.3% vs 2.9%; P<0.001). In multivariate
      analyses, Blacks compared to Whites (OR =0.59, 95% CI =0.42-0.83, P=0.002) and
      uninsured patients compared to privately insured (OR =0.60, 95% CI =0.36-0.98,
      P=0.043) had significantly less CPM. CONCLUSION: CPM rates were significantly
      different among patients of different race, socio-economic class, and insurance
      coverage. This observation is not accounted for by population distribution,
      incidence or disease stage. More in-depth study of the causes of these
      disparities in health care choice and delivery is critically needed.

PMID- 25609998
TI  - Lung and colorectal cancer treatment and outcomes in the Veterans Affairs health
      care system.
AB  - Lung cancer (LC) and colorectal cancer (CRC) are the second- and third-most
      commonly diagnosed cancers in the Veterans Affairs (VA) health care system. While
      many studies have evaluated the treatment quality and outcomes of various aspects
      of VA LC and CRC care, there are no known reviews synthesizing this information
      across studies. The purpose of this literature review was to describe LC and CRC
      treatment (ie, surgical and nonsurgical) and outcomes (eg, mortality,
      psychosocial, and other) in the VA health care system as reported in the existing
      peer-reviewed scientific literature. We identified potential articles through a
      search of published literature using the PubMed electronic database. Our search
      strategy identified articles containing Medical Subject Headings terms and
      keywords addressing veterans or veterans' health and LC and/or CRC. We limited
      articles to those published in the previous 11 years (January 1, 2003 through
      December 31, 2013). A total of 230 articles were retrieved through the search.
      After applying the selection criteria, we included 74 studies (34 LC, 47 CRC, and
      seven both LC and CRC). VA provides a full array of treatments, often with better
      outcomes than other health care systems. More work is needed to assess patient
      reported outcomes. 

PMID- 25609999
TI  - Adherence with ethinylestradiol 20 MUg/drospirenone 3 mg in a flexible extended
      regimen supported by the use of a digital tablet dispenser with or without
      acoustic alarm: an open-label, randomized, multicenter study.
AB  - OBJECTIVE: To evaluate the effect of a digital dispenser's acoustic alarm
      function on adherence to ethinylestradiol (EE) 20 MUg/drospirenone 3 mg in a
      flexible extended regimen (EE/drospirenoneFlex) among women in five European
      countries (France, Germany, Italy, Spain, UK) seeking oral contraception. STUDY
      DESIGN: Randomized, parallel-group open-label study. METHODS: Women aged 18-35
      years received EE/drospirenoneFlex administered in a regimen with cycle lengths
      of their choice with the aid of a digital pill dispenser over 1 year. In group A
      (N=250), the dispenser's acoustic alarm was activated (ie, acoustic alarm +
      visual reminder). In group B (N=249), the acoustic alarm was deactivated (ie,
      visual reminder only). In addition, the women recorded pill intake daily in diary
      cards. The primary efficacy variable was the mean delay of daily pill release
      after the dispenser reminded the woman to take a pill (reference time). Secondary
      efficacy variables included number of missed pills, contraceptive efficacy,
      bleeding pattern, tolerability, and user satisfaction. RESULTS: Dispenser data
      showed a mean (standard deviation [SD]) daily delay in pill release of 88 (126)
      minutes in group A vs 178 (140) minutes in group B (P<0.0001). Median (lower
      quartile, Q1; upper quartile, Q3) number of missed pills was 0 (0; 1) in group A
      vs 4 (1; 9) in group B (P<0.0001). Diary card results revealed similar trends;
      however, underreporting of missed pills was evident in both groups. No
      pregnancies were reported during 424 women-years of exposure. Across the two
      groups, the mean (SD) EE/drospirenoneFlex cycle length was 51.0 (31.8) days with
      strong regional differences, and the mean (SD) number of bleeding/spotting days
      was 50.4 (33.0) days. EE/drospirenoneFlex was well tolerated, and 80% of women
      were satisfied with treatment. CONCLUSION: The dispenser's activated acoustic
      alarm improved adherence with daily tablet intake of EE/drospirenoneFlex,
      reducing missed pills. EE/drospirenoneFlex provided effective contraception and a
      good tolerability profile.

PMID- 25610000
TI  - Is routine antenatal venereal disease research laboratory test still justified?
      Nigerian experience.
AB  - OBJECTIVE: To determine the seroreactivity of pregnant women to syphilis in order
      to justify the need for routine antenatal syphilis screening. METHODS: A
      multicenter retrospective analysis of routine antenatal venereal disease research
      laboratory (VDRL) test results between 1 September 2010 and 31 August 2012 at
      three specialist care hospitals in south-east Nigeria was done. A reactive VDRL
      result is subjected for confirmation using Treponema pallidum hemagglutination
      assay test. Analysis was by Epi Info 2008 version 3.5.1 and Stata/IC version 10.
      RESULTS: Adequate records were available regarding 2,156 patients and were thus
      reviewed. The mean age of the women was 27.4 years (+/-3.34), and mean
      gestational age was 26.4 weeks (+/-6.36). Only 15 cases (0.70%) were seropositive
      to VDRL. Confirmatory T. pallidum hemagglutination assay was positive in 4 of the
      15 cases, giving an overall prevalence of 0.19% and a false-positive rate of
      73.3%. There was no significant difference in the prevalence of syphilis in
      relation to maternal age and parity (P>0.05). CONCLUSION: While the prevalence of
      syphilis is extremely low in the antenatal care population at the three
      specialist care hospitals in south-east Nigeria, false-positive rate is high and
      prevalence did not significantly vary with maternal age or parity. Because
      syphilis is still a serious but preventable and curable disease, screening with
      VDRL alone, without confirmatory tests may not be justified. Because of the
      increase in the demand for evidence-based medicine and litigation encountered in
      medical practice, we may advocate that confirmatory test for syphilis is
      introduced in routine antenatal testing to reduce the problem of false positives.
      The government should increase the health budget that will include free routine
      antenatal testing including the T. pallidum hemagglutination assay.

PMID- 25610001
TI  - Eribulin for the treatment of metastatic breast cancer: an update on its safety
      and efficacy.
AB  - Breast cancer remains a leading cause of cancer-related death internationally.
      Treatment approaches for metastatic breast cancer have evolved in recent years;
      however chemotherapy remains a core component for the majority of patients.
      Agents such as anthracyclines and taxanes have been extensively studied and form
      standard treatment. Eribulin mesylate is a novel synthetic microtubule-directed
      chemotherapy, based on a naturally-occurring compound. Through phase I studies,
      eribulin was found to be tolerable and activity was seen in patients with
      metastatic breast cancer. Phase II studies in metastatic breast cancer further
      demonstrated its efficacy, with responses and survival which compare favorably
      with other studied chemotherapy agents. The phase III EMBRACE study showed
      superior survival for patients treated with eribulin compared with those who
      received a physician's choice control. This led to its approval for use in many
      countries in this setting. Its toxicity profile is well established and
      manageable for the most part, with the commonest reported toxicities being
      alopecia, fatigue, neutropenia and peripheral neuropathy. A second reported phase
      III study comparing eribulin to capecitabine failed to show an improvement in
      survival in pretreated patients. This article reviews the clinical pharmacology
      and mechanism of action of eribulin, and summarizes the results of the major
      preclinical and clinical studies of eribulin in metastatic breast cancer. 

PMID- 25610002
TI  - Cost effectiveness of endometrial ablation with the NovaSure((r)) system versus
      other global ablation modalities and hysterectomy for treatment of abnormal
      uterine bleeding: US commercial and Medicaid payer perspectives.
AB  - OBJECTIVES: Abnormal uterine bleeding (AUB) interferes with physical, emotional,
      and social well-being, impacting the quality of life of more than 10 million
      women in the USA. Hysterectomy, the most common surgical treatment of AUB, has
      significant morbidity, low mortality, long recovery, and high associated health
      care costs. Global endometrial ablation (GEA) provides a surgical alternative
      with reduced morbidity, cost, and recovery time. The NovaSure((r)) system
      utilizes unique radiofrequency impedance-based GEA technology. This study
      evaluated cost effectiveness of AUB treatment with NovaSure ablation versus other
      GEA modalities and versus hysterectomy from the US commercial and Medicaid payer
      perspectives. METHODS: A health state transition (semi-Markov) model was
      developed using epidemiologic, clinical, and economic data from commercial and
      Medicaid claims database analyses, supplemented by published literature. Three
      hypothetical cohorts of women receiving AUB interventions were simulated over 1-,
      3-, and 5-year horizons to evaluate clinical and economic outcomes for NovaSure,
      other GEA modalities, and hysterectomy. RESULTS: Model analyses show lower costs
      for NovaSure-treated patients than for those treated with other GEA modalities or
      hysterectomy over all time frames under commercial payer and Medicaid
      perspectives. By Year 3, cost savings versus other GEA were $930 (commercial) and
      $3,000 (Medicaid); cost savings versus hysterectomy were $6,500 (commercial) and
      $8,900 (Medicaid). Coinciding with a 43%-71% reduction in need for re-ablation,
      there were 69%-88% fewer intervention/reintervention complications for NovaSure
      treated patients versus other GEA modalities, and 82%-91% fewer versus
      hysterectomy. Furthermore, NovaSure-treated patients had fewer days of work
      absence and short-term disability. Cost-effectiveness metrics showed NovaSure
      treatment as economically dominant over other GEA modalities in all
      circumstances. With few exceptions, similar results were shown for NovaSure
      treatment versus hysterectomy. CONCLUSION: Model results demonstrate strong
      financial favorability for NovaSure ablation versus other GEA modalities and
      hysterectomy from commercial and Medicaid payer perspectives. Results will
      interest clinicians, health care payers, and self-insured employers striving for
      cost-effective AUB treatments.

PMID- 25610003
TI  - Seroprevalence of rubella-specific IgM and IgG antibodies among pregnant women
      seen in a tertiary hospital in Nigeria.
AB  - BACKGROUND: Rubella is a contagious viral infection that in pregnant women leads
      to the infection of a developing fetus, causing fetal death or congenital rubella
      syndrome. OBJECTIVE: Pregnant women are not routinely screened for rubella in
      Nigeria. Epidemiological data on rubella is therefore necessary to create
      awareness and sensitize health care administrators and providers. MATERIALS AND
      METHODS: A cross-sectional study was carried out at Ahmadu Bello University
      Teaching Hospital between June and August 2012 to determine the prevalence of
      immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to rubella virus in
      pregnant women using enzyme-linked immunosorbent assay kits. Seroprevalence was
      compared among 160 pregnant women attending the antenatal clinic of Ahmadu Bello
      University Teaching Hospital and 20 nonpregnant women of childbearing age
      studying at Ahmadu Bello University. Prior to sample collection, questionnaires
      were administered to the women to obtain data on sociodemographics, awareness and
      knowledge of rubella, possible risk factors, and clinical symptoms associated
      with the viral infection. RESULTS: Of the 160 pregnant women, 149 (93.1%) and 62
      (38.8%) were positive for anti-rubella IgM and IgG antibodies, respectively.
      Similarly, of the 20 nonpregnant women, 18 (90%) and eight (40%) were positive
      for rubella IgG and IgM antibodies, respectively. None of the possible risk
      factors studied were significantly associated with infection. Age and other
      sociodemographic factors were of little significance, and awareness of rubella
      was low. CONCLUSION: The prevalence of rubella was high in both pregnant (93.1%)
      and nonpregnant women (90%), suggesting sustained transmission, which further
      suggests endemicity. The presence of rubella IgM and IgG antibodies in pregnant
      women predisposes babies to congenital rubella syndrome and emphasizes the need
      for the initiation of a national rubella vaccination program in Nigeria.

PMID- 25610004
TI  - Hyperandrogenism in female athletes with functional hypothalamic amenorrhea: a
      distinct phenotype.
AB  - OBJECTIVE: To compare the reproductive, metabolic, and skeletal profiles of young
      athletic women with functional hypothalamic amenorrhea (FHA) as well as clinical
      or biochemical hyperandrogenism (FHA-EX+HA) with body mass index matched women
      with FHA due to exercise (FHA-EX) or anorexia nervosa (FHA-AN) alone. DESIGN:
      Retrospective cohort study. SETTING: Tertiary care teaching hospital. POPULATION:
      Adolescents and young women, 15-30 years of age, diagnosed with FHA along with
      concurrent signs of hyperandrogenism (n=22) and body mass index matched control
      groups consisting of 22 women in each group of FHA-EX and FHA-AN. MAIN OUTCOMES:
      1) Reproductive hormone profile: luteinizing hormone (LH), follicle stimulating
      hormone (FSH), total testosterone, pelvic ultrasound features. 2) Metabolic
      function and skeletal health markers: fasting glucose, cholesterol, number of
      stress fractures and bone mineral density as assessed by spine dual-energy X-ray
      absorptiometry z scores. RESULTS: FHA-EX+HA group was older at diagnosis compared
      to the other groups with a median (interquartile range [IQR]) age of 22 (18.75
      25.25) years versus (vs) 17.5 (15.75-19) for FHA-EX; (P<0.01) and 18 (16-22.25)
      years for FHA-AN (P=0.01). There were no differences among the groups based on
      number of hours of exercise per week, type of physical activity or duration of
      amenorrhea. Median (IQR) LH/FSH ratio was higher in FHA-EX+HA than both other
      groups, 1.44 (1.03-1.77) vs 0.50 (0.20-0.94) for FHA-EX and 0.67 (0.51-0.87) for
      FHA-AN (P<0.01 for both). Total testosterone concentrations were not different
      among the groups. Median (IQR) fasting serum glucose concentration was higher in
      FHA-EX+HA vs FHA-EX, 88.5 mg/dL (82.8-90 mg/dL) vs 83.5 mg/dL (78.8-86.3 mg/dL)
      (P=0.01) but not different from FHA-AN (P=0.31). Percentage of women with stress
      fractures was lower in FHA-EX+HA (4.5%) as compared to both FHA-EX (27.3%) and
      FHA-AN (50%); P=0.04 and 0.01 respectively. The LH/FSH ratio was weakly
      positively associated with serum glucose (adjusted r (2)=0.102; P=0.01) as well
      as with dual-energy X-ray absorptiometry spine score (adjusted r (2)=0.191;
      P=0.04) in the entire cohort. CONCLUSION: In a small cohort of female athletes
      with hyperandrogenism, a distinct reproductive hormone profile consisting of
      higher LH to FHS ratio may be associated with adverse metabolic health markers
      but improved skeletal health.

PMID- 25610005
TI  - Bilateral septic knee arthritis after treatment of an ectopic pregnancy with
      methotrexate.
AB  - We describe a case of bilateral septic knee arthritis that followed the
      administration of methotrexate for nonsurgical termination of an ectopic
      pregnancy. We believe that methotrexate is a relatively effective alternative to
      surgery in patients with early unruptured tubal pregnancies, but suggest that it
      be used with caution in view of possible septic events. 

PMID- 25610006
TI  - Device-length changes and implant function following surgical implantation of the
      KineSpring in cadaver knees.
AB  - INTRODUCTION: The KineSpring implant system has been shown to provide load
      reductions at the medial compartment of the knee, and has demonstrated clinical
      success in reducing pain and increasing function in patients with medial knee
      osteoarthritis. These results depend on the ability of the KineSpring to rotate,
      lengthen, and shorten to accommodate knee motions, and in response to knee
      position and loading. PURPOSE: The present study was undertaken to determine
      length changes of the implanted KineSpring in response to a range of knee
      positions, external knee loads, and placements by different orthopedic surgeons.
      MATERIALS AND METHODS: KineSpring system components were implanted in ten cadaver
      leg specimens by ten orthopedic surgeons, and absorber-length changes were
      measured under combined loading and in different positions of the knee. RESULTS
      AND CONCLUSION: Spring compression consistent with knee-load reduction, and
      device lengthening and shortening to accommodate knee loads and motions were
      seen. These confirm the functionality of the KineSpring when implanted medially
      to the knee.

PMID- 25610008
TI  - The burden of insomnia in Japan.
AB  - OBJECTIVES: Several studies have suggested that patients who experience insomnia
      report a number of significant impairments. However, despite this literature,
      fewer studies have focused on the burden of insomnia among patients in Japan. The
      objective of the current study is to extend this work in Japan to further
      understand the effect of insomnia on health-related quality of life (hrQOL).
      Further, another objective is to understand general predictors of hrQOL among
      patients with insomnia. METHODS: Data from the 2012 Japan National Health and
      Wellness Survey, an annual, cross-sectional study of adults aged 18 years or
      older, were used (N=30,000). All National Health and Wellness Survey respondents
      were categorized based on the incidence of self-reported insomnia diagnosis and
      prescription medication usage (clinical insomniacs under treatment versus [vs]
      good sleepers without insomnia or insomnia symptoms). Comparisons among different
      groups were made using multiple regression models controlling for demographics
      and health history. RESULTS: Clinical insomniacs (n=1,018; 3.4%) reported
      significantly worse hrQOL compared with good sleepers (n=20,542) (mental
      component summary: 34.2 vs 48.0; physical component summary: 48.0 vs 52.8; health
      utilities: 0.61 vs 0.76; all P<0.05). Health behaviors (smoking, exercise,
      alcohol use) and comorbidities were the strongest predictors of health utilities
      for clinical insomniacs. For all three clinical insomniac subgroups of interest,
      those with a physical comorbidity but not a psychiatric one, those with a
      psychiatric comorbidity but not a physical one, and those without either a
      physical or psychiatric comorbidity, large decrements in health utilities were
      observed for respondents who did not engage in any positive health behaviors
      (0.61, 0.57, 0.64, respectively) relative to good sleepers (0.78). However, the
      gap in health utility scores between these subgroups and good sleepers diminishes
      with an increasing number of positive health behaviors (eg, clinical insomniacs
      with a physical comorbidity but not a psychiatric comorbidity performing all
      three positive health behaviors =0.67 vs good sleepers =0.78). DISCUSSION: A
      significant burden remains for those with insomnia who are treated. Given the
      particularly low levels of hrQOL among treated insomnia patients who have poor
      health behavior profiles and have psychiatric comorbidities, physicians should
      place particular emphasis on these patients who are most in need of intervention.
      Improved treatments may help to address the unmet needs of these patient
      populations.

PMID- 25610007
TI  - Brain delivery of small interfering ribonucleic acid and drugs through intranasal
      administration with nano-sized polymer micelles.
AB  - Recently, the development of effective strategies for enhancing drug delivery to
      the brain has been a topic of great interest in both clinical and pharmaceutical
      fields. In this review, we summarize our studies evaluating nose-to-brain
      delivery of drugs and small interfering ribonucleic acids in combination with
      cell-penetrating peptide-modified polymer micelles. Our findings show that the
      use of polymer micelles with surface modification with Tat peptide in the
      intranasal administration enables the non-invasive delivery of therapeutic agents
      to the brain by increasing the transfer of the administered drug or small
      interfering ribonucleic acid to the central nervous system from the nasal cavity.

PMID- 25610009
TI  - Exploring quality of life as an intervention outcome among women with stress
      related disorders participating in work rehabilitation.
AB  - BACKGROUND: Findings from quality of life studies are often inconclusive for
      reasons such as: i) estimates may address different aspects of quality of life
      and thus produce different outcomes; ii) quality of life is largely determined by
      self-factors; and iii) people with a long-term condition rate their quality of
      life better than those who have had their condition for a short duration. This
      makes quality of life a complex phenomenon to measure. AIMS: The above
      explanations served as hypotheses for this methodologically oriented paper, based
      on a longitudinal study on women with stress-related disorders receiving work
      rehabilitation. METHODS: Eighty-four women participating in a lifestyle
      intervention or care as usual were compared. Self-ratings of "general quality of
      life" and a summarized "satisfaction with different life domains" index
      (according to Manchester Short Assessment of Quality of Life) and two self
      factors (self-esteem and self-mastery) were administered at admission and a 6
      month follow-up. Participant age and amount of months on sick leave prior to
      rehabilitation were used as two proxies of duration of the condition. RESULTS:
      General quality of life distinguished between the groups, whereas satisfaction
      with life domains did not. Self-esteem and self-mastery were related to both
      quality of life aspects. Age was related to both estimates of quality of life,
      whereas duration of sick leave was unrelated to both. CONCLUSION: General quality
      of life and satisfaction with life domains produced different results. Outcome
      studies should apply more than one operationalization of quality of life and self
      factors should be considered as important determinants of quality of life.
      Duration of the condition needs to be acknowledged as well when interpreting
      levels of quality of life, although the current study could not present any clear
      cut findings in this respect.

PMID- 25610010
TI  - Leading teams during simulated pediatric emergencies: a pilot study.
AB  - PURPOSE: Leadership has been identified as a key variable for the functioning of
      teams and as one of the main reasons for success or failure of team-based work
      systems. Pediatricians often function as team leaders in the resuscitation of a
      critically ill child. However, pediatric residents often report having little
      opportunity to perform in the role of team leader during residency. In order to
      gain more insight into leadership skills and behaviors, we classified leadership
      styles of pediatric residents during simulated emergencies. METHODS: We conducted
      a prospective quantitative study to investigate leadership styles used by
      pediatric residents during simulated emergencies with clinical deterioration of a
      child at a pediatric ward. Using videotaped scenarios of 48 simulated critical
      events among 12 residents, we were able to classify verbal and nonverbal
      communication into different leadership styles according to the situational
      leadership theory. RESULTS: The coaching style (mean 54.5%, SD 7.8) is the most
      frequently applied by residents, followed by the directing style (mean 35.6%, SD
      4.1). This pattern conforms to the task- and role-related requirements in our
      scenarios and it also conforms to the concept of situational leadership. We did
      not find any significant differences in leadership style according to the
      postgraduate year or scenario content. CONCLUSION: The model used in this pilot
      study helps us to gain a better understanding of the development of effective
      leadership behavior and supports the applicability of situational leadership
      theory in training leadership skills during residency.

PMID- 25610011
TI  - Relationships between the quality of blended learning experience, self-regulated
      learning, and academic achievement of medical students: a path analysis.
AB  - PURPOSE: This study examined the relationships between the different aspects of
      students' course experience, self-regulated learning, and academic achievement of
      medical students in a blended learning curriculum. METHODS: Perceptions of
      medical students (n=171) from the Royal College of Surgeons in Ireland, Medical
      University of Bahrain (RCSI Bahrain), on the blended learning experience were
      measured using the Student Course Experience Questionnaire (SCEQ), with an added
      e-Learning scale. In addition, self-regulated learning was measured using the
      Motivated Strategies for Learning Questionnaire (MSLQ). Academic achievement was
      measured by the scores of the students at the end of the course. A path analysis
      was created to test the relationships between the different study variables.
      RESULTS: Path analysis indicated that the perceived quality of the face-to-face
      component of the blended experience directly affected the motivation of students.
      The SCEQ scale "quality of teaching" directly affected two aspects of motivation:
      control of learning and intrinsic goal orientation. Furthermore, appropriate
      course workload directly affected the self-efficacy of students. Moreover, the e
      Learning scale directly affected students' peer learning and critical thinking
      but indirectly affected metacognitive regulation. The resource management
      regulation strategies, time and study environment, and effort regulation directly
      affected students' examination scores (17% of the variance explained). However,
      there were no significant direct relationships between the SCEQ scales and
      cognitive learning strategies or examination scores. CONCLUSION: The results of
      this study will have important implications for designing blended learning
      courses in medical schools.

PMID- 25610013
TI  - The effect of L-carnitine treatment on levels of malondialdehyde and glutathione
      in patients with age related macular degeneration.
AB  - OBJECTIVE: The aim of this study was to determine the antioxidant properties of
      the L-carnitine (LC) in the treatment of patients with age-related macular
      degeneration (AMD). MATERIALS AND METHODS: This study involved 60 patients
      diagnosed with early AMD. The patients were divided into two groups. Group I was
      the study group that received LC supplementation for 3 months. Group II was the
      control group and did not consent to LC supplementation over the 3 months. At the
      end of the 3-month period, markers of lipid peroxidation, malondialdehyde (MDA)
      and reduced glutathione (GSH) were measured in the two groups. RESULTS: In the
      study group, the MDA level was significantly reduced, while the GSH level was
      significantly increased at the end of the 3-month period (P<0.001). CONCLUSION:
      Our results suggest that LC may protect against oxidative damage by decreasing
      the MDA level, a marker of lipid peroxidation, and increasing GSH.

PMID- 25610014
TI  - Prognostic importance of increased cyclooxygenase-2 levels in colorectal
      carcinomas: a 5-year single-institution study.
AB  - OBJECTIVE: COX-2-selective inhibitors are used in the prevention and management
      of colorectal carcinogenesis. Our objective was to investigate if COX-2 levels
      have prognostic value in patients diagnosed with colorectal carcinoma. MATERIALS
      AND METHODS: This is a retrospective study of 112 patients diagnosed with
      colorectal carcinoma between 2000-2004 from the General Surgery Department at
      Haydarpasa Training Hospital, Gulhane Military Medical Academy. Patients were
      assessed according to age, gender, localization of the tumor, stage of the tumor,
      remote metastasis status, patient survival, COX-2 levels and grade of
      differentiation. RESULTS: COX-2 levels significantly affect the duration of
      survival (P=0.026) and overall survival (P=0.013). The COX-2 significance value
      showed a tendency to change from negative to positive while a statistically
      meaningful decrease was observed in the survival value (r=-0.25; P=0.007) in
      groups related with the survival duration of cases (r=-0.24; P=0.01). The median
      survival was 36 (26.35-45.65) months. During the examination of survival statuses
      of cases, a statistically meaningful difference was determined between patients
      whom were alive and dead (P=0.01). CONCLUSION: We conclude that COX-2 levels are
      a negative predictor of survival.

PMID- 25610012
TI  - New developments in the management of opioid dependence: focus on sublingual
      buprenorphine-naloxone.
AB  - Opioid maintenance therapy is a well-established first-line treatment approach in
      opioid dependence. Buprenorphine, a partial opioid agonist, has been found by
      numerous studies to be an effective and safe medication in the treatment of
      opioid dependence. At present, buprenorphine is available as a monodrug or in a
      fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and
      abuse for the buprenorphine-naloxone combination is likely but not firmly
      established. Conventional formulations are given sublingually to avoid the
      hepatic first-pass effect. A novel film tablet is available only in the US and
      Australia. Other novel, sustained-release formulations (implant, depot) are
      currently being developed and tested. Recent studies, including a Cochrane meta
      analysis, suggest that the retention with buprenorphine is lower than for
      methadone, but that buprenorphine may be associated with less drug use. Higher
      doses of buprenorphine are associated with better retention rates. Buprenorphine
      has a ceiling effect at the opioid receptor with regard to respiratory
      depression, and may cause fewer fatal intoxications than methadone. Possible
      antidepressant effects of buprenorphine and its use in comorbid psychiatric
      patients has not been studied in much detail. Clinical implications are
      discussed. 

PMID- 25610015
TI  - Paraoxonase and arylesterase activities in patients with preeclampsia.
AB  - OBJECTIVE: Paraoxonase is a high density lipoprotein-associated anti-oxidant
      enzyme. The aim of this study was to investigate the serum paraoxonase and
      arylesterase activities and associations between these enzymes and lipid
      hydroperoxide (LOOH) in preeclamptic patients. MATERIALS AND METHODS: The study
      included 47 preeclamptic (25 severe and 22 mild preeclampsia cases) and 20
      normotensive healthy pregnant women. Serum paraoxonase and arylesterase
      activities and LOOH levels were measured. RESULTS: While serum paraoxonase and
      arylesterase activities were significantly lower in both severe and mild
      preeclamptic patients (P<0.05 for both) than those in normal pregnant subjects,
      LOOH levels were significantly higher in severe (P<0.01) and mild preeclampsia
      cases (P<0.05) than in normotensive pregnant subjects. When all subjects were
      evaluated, there was a negative correlation between paraoxonase and LOOH (r=
      0.24, P<0.05) and between arylesterase and LOOH (r=-0.31, P<0.01). CONCLUSION:
      Our results show that serum paraoxonase and arylesterase activities decrease in
      preeclampsia, and this situation may be associated with increased LOOH in these
      patients.

PMID- 25610016
TI  - The impact of adenotonsillectomy on attention-deficit hyperactivity and
      disruptive behavioral symptoms.
AB  - OBJECTIVE: The objective of this study is to investigate the impact of
      adenotonsillectomy on the neuropsychology of children using the Turgay DSM-IV
      Based Child and Adolescent Disruptive Behavioral Disorders Screening and Rating
      Scale (T-DSM-IV-Scale). MATERIALS AND METHODS: Thirty children admitted to an
      otolaryngology clinic for treatment of sleep-disordered breathing or recurrent
      tonsillitis and who underwent adenotonsillectomy were included the study. All
      parents completed the T-DSM-IV-Scale before surgery and after 3 months of
      surgery. The T-DSM-IV-Scale consists of four sub-scales: inattention,
      hyperactivity, oppositional-defiant disorders, and conduct disorders. SPSS 15 por
      Windows was used to evaluate the datas. RESULTS: Of the 30 children, 17 (56.7%)
      were boys and13 (43.3 %) were girls. The age range was between four and fourteen
      years, and the mean age was 6.6+/-2.6 years. The most common complaints of the
      children in their first admission to the otorhinolaryngology clinic were snoring
      (n = 25, or 83.3%), breathing from the mouth (n = 25, or 83.3%), stuffiness (n =
      16, or 53.3%), post-nasal drip (n = 15, or 50%), halitosis (n = 14, or 46.7%),
      and odontoprisis (n = 12, or 40%). We found a statistically significant
      difference between the mean scores of the inattention, hyperactivity,
      oppositional-defiant disorders, and conduct disorder sub-scales of T-DSM-IV-Scale
      before and three months post-tonsillectomy (P<0.05). CONCLUSION: In SDB
      inattention, hyperactivity and other neurobehavioral problems can be seen. This
      may cause a delay in accurate diagnosis and treatment. Children having
      neurobehavioral problems such as inattention, hyperactivity, oppositional-defiant
      disorders, and conduct disorder symptoms can be assessed for sleep-disordered
      breathing. After adenotonsillectomy, these neurobehavioral problems can improve
      without psychiatric medication; thus, adenotonsillectomy may have a positive
      impact on the neurobehavioral problems of children with sleep-disordered
      breathing.

PMID- 25610017
TI  - Effects of cirrhosis on bone mineral density and bone metabolism.
AB  - OBJECTIVE: The present study was undertaken to examine the correlation between
      the severity of liver disease and the presence and severity of bone disease in
      patients with hepatic cirrhosis. MATERIALS AND METHODS: Between January 2005 and
      February 2006, 40 patients with cirrhosis and 22 healthy controls were enrolled
      in a cross-sectional study. All subjects underwent standard laboratory testing
      and bone densitometric studies of the lumbar spine and femoral neck using dual X
      ray absorptiometry (DEXA). RESULTS: Cirrhotic patients had lower serum follicle
      stimulating hormone (FSH) levels than controls. Male patients had lower serum
      free testosterone (fT) levels than male controls. 25-hydroxyvitamin D (25-OHD3)
      levels were significantly higher in the controls as compared to patients with
      cirrhosis. In the cirrhotic group, 25-OHD3 concentrations did not differ
      significantly between patients with Child B and C class cirrhosis. As compared to
      the control group, cirrhotic patients had significantly elevated levels of
      urinary deoxypyridinoline (DPD). The cirrhotic patients also had a significantly
      lower mean spinal (SD) bone mineral density (BMD) than the control group. BMD of
      the lumbar spine (LS) was noted to be significantly lower in the Child C group
      than in the Child B group. In the cirrhotic patients, there was a positive
      correlation between the BMD T score of the femoral neck (FN) and albumin levels
      whereas there was a negative correlation between BMD T scores of the FN and age,
      bilirubin and prothrombin time (PT). CONCLUSION: Osteopenia and osteoporosis are
      highly prevalent in individuals with liver cirrhosis. Cirrhotic patients should
      undergo routine bone densitometric assessment and, if necessary, be treated for
      osteoporosis.

PMID- 25610018
TI  - Epidemiological factors affecting hepatitis a seroprevalence in childhood in a
      developing country.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence rate of
      hepatitis A virus (HAV) and the socio-epidemiological factors affecting HAV among
      children aged 0-18 years in Eastern Turkey. MATERIALS AND METHODS: The study
      sample consisted of 226 children aged 0-18 years who were registered at the
      Pediatrics Department of Ataturk University Medical Faculty for any reason except
      jaundice between January and May 2002. The presence of anti-HAV immunoglobulin G
      (IgG) in the children was determined by ELISA. RESULTS: The percentage of HAV IgG
      seropositivity among the 226 children was 59.7%. We detected an increase of HAV
      prevalence with age. The prevalence of HAV did not differ significantly in
      relation to gender. HAV prevalence was higher in children of rural areas than in
      children of urban and suburban areas (P<0.001). Only two of the 226 children had
      received the HAV vaccine. The percentage of HAV IgG seropositivity of
      unvaccinated children was 59.3%. HAV seroprevalence was higher in subjects who
      had a history of jaundice (84.6%) than in those who did not (58.2%). An increase
      in HAV prevalence was observed with a decrease in socio-economic status
      (P<0.001). CONCLUSION: HAV prevalence was markedly high, but HAV vaccination of
      children was very low in Erzurum. The socio-demographic factors of age,
      settlement area, and socio-economic status of family were significantly
      associated with HAV prevalence.

PMID- 25610019
TI  - Retrospective evaluation of colon injury cases.
AB  - OBJECTIVE: When considering abdominal region injuries, the colon is one of the
      most frequently wounded organs. Due to the septic contents of the colon, failure
      to treat or improper treatment of colon injuries increases the risk of major
      complications and may result in death. The aim of our study is a retrospective
      evaluation of colon injury cases over a 5-year period. MATERIALS AND METHODS:
      Forty-nine patients with a diagnosis of colon injury were included in the study.
      The cause of colon injury, injured area, Flint colon injury score, additional
      organs injured, type of surgical procedure performed, postoperative complications
      and mortality were evaluated. RESULTS: The most frequent cause of colon injury
      was cutters (57.2%), followed by firearms (36.7%). The left colon was the most
      common site of injury (40.8%), followed by the transverse (28.6%) and right colon
      (20.4%). Primary treatment or resection and primary anastomosis were performed on
      38 patients (77.6%), while primary treatment and proximal decompression colostomy
      were performed on 11 patients (22.4%). Eighteen of the patients (36.7%)
      experienced major postoperative complications, and 6 patients (12.2%) died.
      CONCLUSION: The morbidity and mortality of colonic injuries can be reduced by
      rapid patient transportation, good operational experience, use of wide spectrum
      antibiotics and postoperative care in an intensive care unit.

PMID- 25610020
TI  - Venous malformation between the external and internal jugular vein results in
      swelling: multidetector computed tomography imaging.
AB  - Venous malformation between the external and internal jugular vein characterized
      by nonfluctant, painless, and nonpulsatile swelling on the right side of his neck
      while the individual was singing was reported in a 45-year-old man.
      Interestingly, there was no skin lesion observed on his neck. The swelling
      increased in size when the patient was shouting (Valsalva maneuver) and
      diminished in size during periods of rest. Contrast enhanced multi detector
      computed tomography (MDCT) angiography indicated the presence of a venous
      malformation between the external and internal jugular vein. The patient was
      administered a conservative treatment strategy. Notably, only symptomatic
      malformations or lesions causing important aesthetic prejudice require surgical
      treatment. In this case, there were no symptoms or esthetic issues. Thus, we
      recommend diagnosis using MDCT imaging for vascular malformations at
      contraindicate magnetic resonance imaging (MRI). 

PMID- 25610021
TI  - Ectopic multinodular goiter: multidetector computed tomography findings.
AB  - The thyroid is the first endocrine gland to form during embryogenesis. At this
      stage, incomplete or anomalous migration of thyroid tissue causes ectopic
      localization of the gland. In our case, a 55-year-old woman who was evaluated via
      ultrasonography (USG) and multi-detector computed tomography (MDCT) had no
      thyroid gland at the normal location, but did have ectopic thyroid tissue in the
      left submandibular and submental regions. 

PMID- 25610022
TI  - Adult type granulosa cell tumor of the testis: case report and review of the
      literature.
AB  - Testicular granulosa cell tumors are extremely rare in adults. We report a case
      of a testicular germ cell tumor (GCT) in a 21-year-old man. The tumor was treated
      successfully with radical orchiectomy, and follow-up computed tomography revealed
      no evidence of recurrence or metastasis 10 months postoperatively. The clinical
      and histopathological features, treatment, and prognosis of testicular GCT are
      reviewed in this manuscript. 

PMID- 25610023
TI  - A coincidence of rheumatoid arthritis, autoimmune thyroid disease and vitiligo in
      a single patient: a possible pathogenetic linkage.
AB  - It has been widely observed that disorders with an autoimmune pathogenesis occur
      with increased frequency in patients with a history of another autoimmune disease
      (AD). The numbers of documented cases of a co-occurrence of different autoimmune
      diseases in a single patient in addition to studies investigating the possible
      common etiopathogenesis of these diseases have increased in recent years.
      Available data suggest that the presence of one AD should alert the clinician to
      the possibility of a second AD. In this report, we aimed to draw attention to
      these potential coincidences and the possible pathogenetic linkages between three
      distinct ADs in a single individual diagnosed with rheumatoid arthritis,
      autoimmune thyroid disease and vitiligo. Further documentation of observations of
      possible coincidence are required in order to yield results that may shed light
      on the biological pathways of these diseases. 

PMID- 25610024
TI  - Obstructive jaundice caused by hepatocellular carcinoma with bile duct tumor
      thrombi: a case report.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy and cause of death in the
      developing world. In this report, a case of obstructive jaundice caused by
      hepatocellular carcinoma with bile duct tumor thrombi is presented. 

PMID- 25610025
TI  - Hamartoma - a rare benign tumor of the spleen: a report of four cases.
AB  - Splenic hamartoma is an uncommon benign tumor. We retrospectively analyzed all
      patients who underwent splenectomy between May 2000 and June 2006 and four cases
      of splenic hamartoma were encountered. Three patients presented with mild
      abdominal pain. Abdominal ultrasonography was the first diagnostic step, which
      revealed a splenic mass. Doppler ultrasonography, computed tomography, and
      magnetic resonance were among the other diagnostic methods. An elective
      splenectomy was performed for all of the cases. Splenic hamartoma must be
      considered in the differential diagnosis of splenic masses unrelated to any other
      malignancy. Elective splenectomy is indicated due to hematological disorders or
      symptoms of pain and appreciation of the mass. 

PMID- 25610026
TI  - Hydranencephaly in a newborn with basilar artery occlusion: MRI findings.

PMID- 25610027
TI  - The effects of hypertonic saline solution, ascorbic Acid and low-molecular-weight
      heparin on acute necrotizing pancreatitis in rats.
AB  - OBJECTIVE: We investigated the biochemical and histopathological effects of
      vitamin C, low-molecular-weight heparin (LMWH), and hypertonic solution on acute
      necrotizing pancreatitis and on lungs as a terminal organ. MATERIALS AND METHODS:
      We included 48 Sprague-Dawley rats in the study, which were divided into six
      groups, each with eight rats. The rats in group 1 were sacrificed immediately, in
      order to determine normal reference values for biochemical and histopathological
      data. Twenty-four hours after giving intraperitoneal L-arginine to the remaining
      five groups, development of pancreatitis was shown through assessment of amylase
      and CRP values. Rats in group 2 were sacrificed at the 24th hour and assigned to
      the control group for biochemical or the histopathological data groups, in which
      pancreatitis was induced. The rats in the remaining four groups were given
      intravenous (IV) isotonic NaCl (group 3), IV vitamin C (group 4), subcutaneous
      LMWH (group 5), IV hypertonic NaCl (group 6) between 24-48 hours. Each group was
      assessed with respect to amylase, Serum glutamic oxaloacetic transaminase (SGOT),
      Lactate dehydrogenase (LDH), C-reactive protein (CRP), bicarbonate, base excess
      (BE), Ca++, ascorbic acid, and leukocyte at hour 72. Additionally, pancreatic and
      lung tissue was histopathologically evaluated. RESULTS: In the treatment groups,
      amylase and leukocyte levels at the 72nd hour were found to be significantly
      lower than at the 24th hour (p<0.05). The most significant decrease in amylase
      and leukocyte levels was found in group 6, and damage to the pancreas was found
      to be lowest in groups 4 and 6. CONCLUSION: We observed that in rats, hypertonic
      NaCl solution and vitamin C reduced the amount of necrosis in the pancreas.

PMID- 25610028
TI  - Evaluation of quinolone resistance in gram negative bacilli isolated from
      community- and hospital-acquired infections.
AB  - OBJECTIVE: Gram negative bacilli are among the most important microbial agents
      involved in both hospital- and community-acquired infections. The quinolones are
      preferred antibacterial agents for the treatment of both community- and hospital
      acquired urinary tract infections caused by gram negative bacilli because of
      their strong antibacterial effects, and because they can be administered both
      orally and parenterally. In this study, it was aimed to determine the sensitivity
      of gram negative bacteria isolated from both hospital- and community-acquired
      infections, to quinolones. MATERIALS AND METHODS: Bacterial strains used in this
      study were isolated from pathologic samples of patients who were treated in
      different clinics or who were admitted to the polyclinics of Ataturk University
      Research Hospitals. Susceptibility to ciprofloxacin, levofloxacin, ofloxacin and
      norfloxacin was assessed for all strains included in the study via the Kirby
      Bauer disk diffusion method according to CLSI criteria. RESULTS: Of the 205
      strains tested, 116 (56.5%) were from community-acquired infections, and 89
      (43.5%) were from hospital-acquired infections. Resistance rates of community
      origin strains against ciprofloxacin, ofloxacin and levofloxacin were 25%,
      whereas they were 26.7% against norfloxacin. Ciprofloxacin was the most effective
      quinolone (65.2%) against hospital-origin strains. E. coli was the most commonly
      isolated etiological agent from both community- and hospital-acquired infections.
      CONCLUSION: In this study, resistance to quinolones was observed for gram
      negative bacilli isolated from both hospital- and community-acquired infections,
      with the exception of community-acquired Salmonella and Shigella. Thus, these
      drugs should not be used empirically in the treatment of infections caused by
      gram negative bacilli, and susceptibility test results should be considered when
      planning therapy.

PMID- 25610029
TI  - The Diagnostic Value of Tc-99m MIBI Gated Myocardial Perfusion SPECT in Detection
      of Silent Myocardial Ischemia in Asymptomatic Patients with Type 2 Diabetes
      Mellitus.
AB  - OBJECTIVE: In this study, we aimed to evaluate the diagnostic value of Technetium
      99m methoxyisobutylisonitrile (Tc-99m MIBI) gated myocardial perfusion SPECT
      (MPS) in the detection of coronary artery disease (CAD) and silent myocardial
      ischemia (SMI) in patients with asymptomatic type 2 diabetes mellitus (DM).
      MATERIALS AND METHODS: For this purpose, 35 patients with type 2 DM and 15
      volunteers with no cardiac symptoms (control group) were included in this study.
      Exercise tolerance tests (ETT), echocardiography and Tc-99m MIBI gated MPS were
      performed in patients and volunteers. Computed tomography coronary angiography
      (CTCA) was performed in patients with coronary ischemia or infarct detected by Tc
      99m MIBI gated MPS. The results were analyzed and compared visually and
      statistically. RESULTS: The present study revealed a high rate of silent
      myocardial ischemia (25.71%, N=9) in 35 patients with type 2 DM. Severe CAD in
      CTCA was detected in four of nine patients with ischemia or infarct by Tc-99m
      MIBI gated MPS (44.4%). Left ventricular diastolic dysfunction, ischemic pattern
      and high risk of CAD were detected in the same four patients by echocardiography,
      ETT and biochemical analysis, respectively. At the end of the statistical
      evaluation, we found that Tc-99m MIBI gated MPS showed significant correlations
      with CTCA, echocardiography, ETT, Hba1c level, risk of CAD and diabetic age in
      diabetic patients with CAD. CONCLUSION: We propose that Tc-99m MIBI gated MPS is
      a reliable and non-invasive method that can be used to detect silent myocardial
      ischemia and CAD in patients with type 2 DM.

PMID- 25610030
TI  - The Influence of Age on Behcet's Disease Activity.
AB  - OBJECTIVE: Behcet's disease (BD) is a multi-systemic vasculitis characterized by
      a relapsing and remitting, rather than a persisting, disease course. It is
      thought that BD activity decreases as the age of the afflicted individual
      increases. Furthermore, disease severity is reported to be greater in individuals
      that first present with the disease at a young age. This study investigates the
      association between disease activity scores and both the current ages of BD
      patients and patient age at disease onset. MATERIALS AND METHODS: Fifty patients
      with BD participated in this study. The gender, age, and age at disease onset of
      each patient was recorded. A BD Current Activity Form (BDCAF) was used to assign
      a clinical disease activity score for all enrolled patients. The participants
      were divided into subgroups according to 1) their current ages and 2) their ages
      at the onset of BD disease. In addition to BDCAF scores, erythrocyte
      sedimentation rates (ESR) and C-reactive protein (CRP) levels were compared
      across groups. Statistical analyses were performed using one-way ANOVA. RESULTS:
      The mean patient age and the mean patient age at the time of disease onset were
      34.68+/-9.71 and 26.10+/-7.07 years, respectively. Patients that were younger
      than 30 years of age exhibited significantly higher rates of oral ulceration and
      arthralgia, and had higher total BDCAF scores than patients that were older than
      40 years of age (p=0.038, p=0.020, and p=0.026, respectively). Patients who
      developed BD before their twentieth year showed significantly higher total
      disease activity scores than patients in the oldest age at disease onset group (p
      < 0.05). No significant difference was observed in ESR and CRP levels between
      groups. CONCLUSION: Our results demonstrate that younger BD patients and patients
      that first present with disease symptoms at a younger age have higher disease
      activity scores. Our results reinforce the importance of considering the age at
      disease onset when clinically treating individuals with BD.

PMID- 25610031
TI  - Hyperemesis Incidence in Planned versus Unplanned Pregnancy.
AB  - OBJECTIVE: We evaluated the incidence of hyperemesis between planned and
      unplanned pregnancy. MATERIALS AND METHODS: A prospective study was conducted
      among 100 women with planned pregnancies and 100 women with unplanned
      pregnancies. Participants completed a questionnaire to determine the presence of
      vomiting. If pregnant women had severe vomiting (>3 times per day), urinary
      investigation was performed; at least one positive ketonuria was considered as
      hyperemesis. RESULTS: There was a significant difference between planned and
      unplanned pregnancy in terms of the incidence of hyperemesis (p=0.0001). Women
      with unplanned pregnancies had a more than 18-fold increased risk of hyperemesis
      (OR=18.88; %95 CI, 8.84-40.31) compared to women with planned pregnancies.
      CONCLUSION: Healthy women may be able to improve their management of hyperemesis
      during pregnancy if they plan their pregnancies.

PMID- 25610032
TI  - The use of harmonic scalpels in thyroidectomies: clinical experiences.
AB  - OBJECTIVE: Many studies have been conducted to investigate the efficacy of
      harmonic scalpels in thyroidectomies. Here, we present our clinical experiences
      with the instrument. MATERIALS AND METHODS: The study was conducted at the
      General Surgery Department of the Ataturk University School of Medicine between
      January 2005 and July 2008. It was a prospective, randomized, controlled study.
      Patients with benign nodular goiter (BNG) were included in the study and randomly
      divided into three groups. The first group consisted of 47 patients, the second
      group consisted of 57 patients, and the third group consisted of 41 patients.
      Patients in the first group underwent the classical thyroidectomy. Those in the
      second group had only the superior thyroid arteries and veins ligated (with silk
      or polyglactin), while the other vascular structures were divided using a
      harmonic scalpel. In the third group, all arteries and veins of the thyroid gland
      were divided using a harmonic scalpel. In each group, mean operation time, amount
      of bleeding, amount of postoperative drainage, and other postoperative
      complications were recorded. RESULTS: Operation time was significantly lower for
      patients in the third group. The degree of bleeding and postoperative drainage
      was lower in the second and third groups with respect to the first group. There
      was no significant difference among the groups in terms of the development of
      transient hypocalcemia or voice impairment. CONCLUSION: We conclude that the use
      of harmonic scalpels for a thyroidectomy is safe, shortens operative time, and
      decreases intraoperative bleeding.

PMID- 25610033
TI  - Neopterin levels in patients with cerebrovascular disease.
AB  - OBJECTIVE: The recovery period in ischemic cerebrovascular disease is sometimes
      long and complicated. It is thought that a systemic inflammatory response plays
      an important role in this process. Therefore, promising studies have reported
      that neopterin and other cytokines serve as indicators of the inflammatory
      response. The present study investigated the effects of cerebrovascular diseases
      on plasma neopterin. MATERIALS AND METHODS: We studied 68 consecutive patients
      under 65 years of age with cerebrovascular disease; the mean age was 52.08+/-5.74
      years (yrs) (ranging from 39 yrs to 64 yrs; 28 female and 40 male). We also
      studied 29 randomly selected age-matched healthy subjects (control); the mean age
      was 49.76+/-13.11 years (yrs) (ranging from 41 yrs to 62 yrs; 12 female and 17
      male). Blood samples for assessing plasma levels of neopterin were usually taken
      within seven days after admission to the hospital and stored at -20 degrees C
      until analysis. Serum neopterin levels in all the subjects were measured by
      Enzyme Immunoassay (EYA) using the BRAHMS method (Neopterin; Diagnostic GmbH,
      16761 Berlin, Germany). Differences between the groups' means were analyzed with
      the Mann-Whitney U test. RESULTS: The mean values of neopterin levels in patients
      (mean neopterin levels in patients, 18.51 +/- 11.56 nmol/L; vs. control, 12.26 +/
      3.87 nmol/L [p=.001]) were significantly different when compared with the
      controls. CONCLUSION: It has been suggested that the mortality and morbidity
      associated with cerebrovascular disease could be prevented by a reduction in the
      inflammatory response. We suggest that plasma neopterin levels were significantly
      increased. So, the levels of plasma neopterin may be useful monitoring of
      treatment and course of diseases.

PMID- 25610034
TI  - Dobutamine stress echocardiography and tissue synchronization imaging.
AB  - Dobutamine stress echocardiography has emerged as a reliable method for the
      diagnosis of coronary artery disease and the management of its treatment. Several
      studies have shown that that this technique works with 80-85% accuracy in
      comparison with other imaging methods. There are few studies aimed at developing
      the clinical utility of dobutamine stress echocardiography for the evaluation of
      normal and abnormal segments that result from dobutamine stress with Tissue
      Synchronization Imaging. 

PMID- 25610035
TI  - Does atherosclerosis contribute the development of Fahr's Syndrome?
AB  - Fahr's syndrome is a rare neurological condition in which calcification of
      vessels in the basal ganglia and cerebellum usually occurs. Impaired glucose
      tolerance (IGT) may be present, causing multiple organ complications by means of
      atherosclerosis. We report a case of Fahr's syndrome associated with
      hypoparathyroidism and IGT. We present the case of a 52-year-old man with Fahr's
      syndrome and IGT. The patient's neurological examination was normal except for
      bilateral tremor. Laboratory investigations showed that the level of serum Ca
      (calcium) was 5.9 mg/dl, the parathormone (PTH) level was 1.95 pg/ml (normal
      level 15-65 pg/ml) and the phosphate (P) level was 5.45 mg/dl (normal level 2-6
      mg/dl). Bilateral and symmetric calcifications in the basal ganglia, the centrum
      semiovale, and the cerebellum were demonstrated with a computerized scan of the
      head (CT) and magnetic resonance imaging (MRI). Therefore, the patient was
      diagnosed with Fahr's syndrome. An endocrinologist was consulted, and treatment
      was started according to the suggestions of the endocrinologist. Here we report a
      case of Fahr's syndrome associated with hypoparathyroidism and IGT.
      Atherosclerosis due to IGT may contribute to the calcification of brain vessels.
      Further investigations will be needed to clarify the pathogenesis of Fahr's
      syndrome. 

PMID- 25610036
TI  - Retroperitoneoscopic live donor nephrectomy: 7 cases.
AB  - Laparoscopic living donor nephrectomy causes less pain, shorter hospital stays
      and a quicker return to daily activities. Because of potential bowel injuries and
      risk of intestinal obstruction secondary to adhesions later on, the
      retroperitoneoscopic donor nephrectomy (RDN) technique has been developed. The
      first 7 RDN cases carried out at our organ transplantation unit between December
      2006 and May 2007 were retrospectively examined. The male/female ratio of the
      patients was 4/3. Left nephrectomy was performed in all cases. In two patients,
      the conventional method was performed because of an adhesion in the hilar area in
      one patient and because of technical difficulty after entering the peritoneum in
      another patient. Serious complications such as massive hemorrhage and intestinal
      injury were not observed. None of the patients required blood transfusion. The
      mean operative time was 161 minutes, with the exception of 2 patients who
      required conversion to other methods. Mean warm ischemia duration was 125
      seconds. Oral feeding began the first postoperative day. The mean inpatient stay
      was 3.5 days. The mean recipient creatinine levels 24 hours and 1 month post
      procedure were 3.78 mg/dl and 1.04 mg/dl, respectively. RDN is technically more
      difficult and has a steeper learning curve compared to transperitoneal donor
      nephrectomy. As our RDN cases increase, we will obtain more representative data
      on complications. 

PMID- 25610037
TI  - Anesthesia and airway management in two cases of apert syndrome: case reports.
AB  - Apert syndrome is a type of acrocephalosyndactilia that consists of craniofacial
      synostosis, midface hypoplasia and syndactyly, with an autosomal dominant
      inheritance pattern. During anesthesia, difficult intubation and ventilation may
      be observed because of abnormal airways. In one of our patients, visceral
      anomalies, such as esophageal stricture and post-strictural dilatation, may cause
      respiratory problems because of aspiration. The second case was a Mallampati
      grade 2 with craniofacial synostoses, midface hypoplasia and syndactyly. In the
      case of apert syndrome, anesthetists must be prepared for intubation
      difficulties, airway and ventilation problems and even visceral anomalies. 

PMID- 25610038
TI  - The Multi-Detector CT findings of giant abdominal lymphangiectasis mimicking a
      mesenteric cystic mass in a patient with midgut volvulus.
AB  - Our purpose is to show the Multi-Detector CT (MDCT) findings of an intra
      abdominal giant cystic lesion with midgut volvulus and to share our experience
      with giant lymphangiectasis mimicking a mesenteric cyst or a cystic mass. The
      pathological evaluation indicated that the cyst contained abdominal lymphatic
      material. Malrotation is usually detected in infants and children, but rarely in
      adults. In patients with chronic and recurrent volvulus, chronic venous
      congestion with lymphatic engorgement may occur. Interference with lymphatic
      drainage may result in formation of a lymphangioma or a chylous mesenteric cyst.
      In our case, because of the intestinal lymphatic torsion, there was a cystic
      lesion mimicking a mesenteric cyst or a cystic mass. To our knowledge, this is
      the first case of midgut volvulus and large mesenteric lymphangiectasis to be
      depicted by MDCT. 

PMID- 25610039
TI  - Possible Subdural Block during Interscalene Brachial Plexus Block: A Case Report.
AB  - The interscalene block technique is widely used for a variety of procedures on
      the upper extremities. In general, this technique is safe and effective but is
      not without hazards. A case of subdural block resulting from an interscalene
      block is presented. In a 60-year-old female patient with carpal tunnel syndrome,
      sudden bradycardia, unconsciousness and respiratory arrest developed within
      several minutes after performing the block. At the end of the postinjectional
      third hour, she regained full consciousness, spontaneous breathing and full
      sensorial functions, except for profound anesthesia in the right arm. Within 6.5
      hours of injection, right arm strength and sensation returned to normal; however,
      analgesia remained until the postinjectional ninth hour. 

PMID- 25610040
TI  - Giant sacrococcygeal teratoma in newborns.

PMID- 25610041
TI  - Effect of photodynamic therapy with posterior sub-tenon triamcinolone acetonide
      on predominantly classic choroidal neovascularization: one-year results.
AB  - OBJECTIVE: The aim of this study was to compare the results of monotherapy
      (photodynamic therapy) and combined therapy (photo-dynamic therapy with posterior
      sub-Tenon triamcinolone acetonide) in age-related macular degeneration (AMD).
      MATERIALS AND METHODS: Forty eyes from forty patients with diagnosed neovascular
      AMD were enrolled in this study during March-2005 - October-2008. All patients
      were grouped in either the study or the control group. Both the study and control
      groups consisted of 20 eyes from 20 patients. The study group was treated with
      posterior sub-Tenon triamcinolone acetonide (PSTA) along with their initial
      photodynamic therapy (PDT) treatment. The control group members were treated with
      PDT alone. All patients were examined at 1, 3, 6 and 12 months. Visual acuity
      (VA), lesion size and number of treatment sessions were recorded during each
      examination. RESULTS: The mean difference between pre- and post-treatment VA
      using the Snellen chart was +0.6 +/- 1.7 in study group and -1.4 +/- 1.7 in
      control. The difference for VA was significant in the study group as compared to
      control (p<0.05). The decrease in lesion size in the study group was 680+/-1195.2
      um, and the decrease was 32.75 +/- 809.9 um in the control. The difference with
      regard to the decrease in lesion sizes was significant in the study group as
      compared to the control (p<0.05). Total PDT treatment sessions were applied 1.2
      times per patient in the study group and 1.9 times per patient in the control
      group. The difference was not significant (p>0.05). CONCLUSION: Our study showed
      that PSTA with PDT significantly reduces CNV growth, and improves VA at the 12
      month follow-up in patients with AMD.

PMID- 25610042
TI  - Stereological Evaluation of Tumor Regression Rates in Lung Cancer Using CT Via
      the Cavalieri Method.
AB  - OBJECTIVE: The aims of this study were to analyze the relevant methods of
      computed tomography (CT) and stereology with respect to the estimation of tumor
      volume and to determine whether the response rates measured by the stereological
      method correlate with those of conventional morphometric techniques in lung
      cancer. MATERIALS AND METHODS: The study group was composed of 32 patients,
      including 25 males and 7 females. All the subjects included were non-small celled
      lung cancer patients (NSCLC), and they were all treated with either chemotherapy
      (n=12) or chemotherapy plus radiotherapy (n=20) for locally advanced disease
      (Stage III A and Stage III B). All patients underwent contrast enhanced CT of the
      thorax before and after treatment. Tumor diameters were measured according to
      stereological methods, the World Health Organization (WHO) criteria and the
      Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: With all three
      methods (stereological method, RECIST and WHO), an improvement was observed in
      the mean tumor size. The response rates were 11.8 +/- 117.5% (stereological
      method), 27.4 +/- 38.8% (RECIST), and 38.7 +/- 68.1% (WHO). Although the response
      rates in RECIST and WHO criteria were statistically significant (P=0.02 and
      P=0.045 for RECIST and WHO, respectively), the response rates with stereological
      measurements were not statistically significant (P=0.21), showing that response
      rates obtained by the Cavalieri method differ from those obtained through WHO and
      RECIST. The comparison between response rates obtained with each method shows
      that the stereological response rate was not correlated with the response rate in
      either RECIST or WHO, (r=-0.15, P=0.59 and r=-0.27, P=0.33 for RECIST and WHO,
      respectively), while there was good correlation between the WHO and RECIST
      response rates (r=0.87 and P<0.001). CONCLUSION: The Cavalieri principle is more
      suitable for the evaluation of tumor volumes in response to treatment in the
      management of advanced malignancies, in particular in patients with tumors of
      irregular shape or when the determination of treatment response is not clear.

PMID- 25610043
TI  - Head-up tilt table testing with sublingual isosorbide dinitrate in the diagnosis
      of vasovagal syncope in children.
AB  - OBJECTIVE: To evaluate the effect of sublingual administration of ISDN on the
      results of the head-up tilt table test (HUTT) in children and adolescents with
      vasovagal syncope. MATERIALS AND METHODS: The study group consisted of 30
      children, each with at least one incidence of vasovagal syncope, and the control
      group had 15 healthy children. The patients were tilted upright at an angle of 60
      degrees  for 15 minutes. If the test was negative, sublingual ISDN was
      administered and the test was continued for an additional 15 minutes. RESULTS:
      The sensitivity and specificity of the basal test were 30% and 100%,
      respectively. Although the specificity decreased somewhat (93.3%) after
      sublingual ISDN, the sensitivity significantly increased to 96.7%. No severe
      complications were observed after sublingual ISDN administration. CONCLUSION: Our
      results suggested that sublingual ISDN is a useful, effective and safe agent for
      pharmacologic stimulation and measurement of the HUTT in children. It increased
      the sensitivity of the test with a slight decrease in specificity.

PMID- 25610044
TI  - Acute nontraumatic chest pain in emergency department and cost-effectiveness
      evaluation.
AB  - OBJECTIVE: Cost-effective use of cardiac markers for the evaluation of ischemic
      chest pain (CP) patients at the emergency department (ED) is attracting the
      attention of researchers. The aim of this study is to define how cost-effective
      an approach should be for evaluate CP patients and to evaluate whether testing
      for cardiac markers is done cost-effectively in CP patients. MATERIALS AND
      METHODS: In this retrospective study, 1028 ischemic CP patients (aged from 17-89
      years, 389 female, 639 male) with non-diagnostic electrocardiography (ECG) who
      were admitted to the ED between September 2002 and September 2003 were enrolled
      into the study. RESULTS: The conditions of how diagnostic tests were actually
      ordered for these patients and how they should have been ordered cost-effectively
      were assessed and both the cost and effectiveness were compared. The actual total
      cost of the diagnostic tests ordered to investigate ischemic CP was $42,476. The
      cost would have been $32,342 if they had been ordered in the most cost-effective
      manner, for a total savings of $10,134. The ED cost, the calculated cost
      effective cost and the lost amount were compared with the Student's t-test, and
      the differences between them was found to be statistically significant (p<0.001).
      The effectiveness was compared using the chi-square test and was found to be
      significant (chi(2)= 12.20, SD= 1, p<0.001). CONCLUSION: In conclusion, fast and
      effective evaluation of ischemic CP in the ED and correct management of patients
      by correct determination of the risk factors provides a high level of cost
      effectiveness. Every ED should determine an algorithm for patients admitted with
      CP and physicians should obey this algorithm.

PMID- 25610045
TI  - Endoscopic versus open approach of bladder cuff and distal ureter in the
      management of upper urinary tract transitional cell carcinoma.
AB  - OBJECTIVE: Nephroureterectomy with the removal of the ipsilateral ureteral
      orifice and bladder cuff en bloc remains the gold standard treatment for upper
      urinary tract urothelial cancer. The distal ureter can be removed with the open
      surgical technique or endoscopic approach. We compared the outcomes of the
      endoscopic approach with those of conventional open surgery on the distal ureter.
      MATERIALS AND METHODS: We collected data from the charts of 30 patients who
      underwent radical nephroureterectomy at our clinic from January 1997 to January
      2007 for upper urinary tract urothelial carcinoma. The patients were divided into
      two groups according to procedure performed on the distal ureter. Group I (n:12)
      was comprised of patients who underwent an open surgical procedure, and group II
      (n:18), was comprised of patients who underwent an endoscopic approach. Both
      groups were compared in terms of operative time, blood loss, transurethral
      catheter duration and duration of hospital stay. RESULTS: Patient age and tumor
      location showed no significant differences between the two groups. The operative
      time was significantly longer in group I than group II (181 versus 128 minutes;
      p<0.05). On the other hand, the estimated blood loss, transurethral catheter
      duration and duration of hospital stay were significantly lower in group II (205
      mL versus 435 mL, 5 versus 8.5 days and 5.6 versus 9.2 days, respectively; p
      <0.05). CONCLUSION: The results of our study show that the endoscopic approach is
      less invasive than open surgery on the distal ureter. This procedure can easily
      be performed in the management of upper urinary tract urothelial carcinoma.

PMID- 25610046
TI  - Can the Function-Morphology Association Be a Model for the Early Detection of
      COPD in Asymptomatic Smokers?
AB  - OBJECTIVE: In the present study, we aimed to evaluate the morphological and
      functional characteristics in symptomatic and asymptomatic smokers in comparison
      to nonsmokers in order to gain better understanding of the pathogenesis and early
      diagnosis of Chronic Obstructive Pulmonary Disease (COPD). MATERIALS AND METHODS:
      A Randomized, double-blind, placebo -controlled, parallel-group trial vas
      performed. PATIENTS AND INTERVENTIONS: A total of 50 male patients (40 smokers
      and 10 non-smokers) who completed a questionnaire, between the ages of 18-60
      (mean age 32), were included the study. Of the smokers, 23 were symptomatic, and
      17 were asymptomatic. High-resolution computerized tomography (HRCT) and
      pulmonary function tests (PFTs) were performed in all cases. RESULTS: In the
      evaluation of all smokers, a comparison of the PFTs and morphological changes
      revealed a significant correlation between all morphological parameters and
      DeltaN2/l. Although a relationship was found between the smoking score and the
      closing volume (CV), DeltaN2/l and anatomic dead space (ADS) in all cases, the
      smoking score was significantly correlated with only the CV in symptomatic cases
      and with only the ADS in asymptomatic cases. There was a positive correlation
      between the emphysema parameters on HRCT and smoking, but no correlation was
      found between the parameters and the pulmonary function tests. CONCLUSION: The
      relationship between morphology and function is better, although different, in
      the asymptomatic period of lung injury caused by smoking compared with the
      symptomatic period, and the relationship is increasingly weakened in the further
      stages of the disease.

PMID- 25610047
TI  - Clinical implications of chest x-ray parameters in evaluating patients with
      cardiac dyspnea.
AB  - OBJECTIVE: To evaluate the relationship between aortic arch calcification and
      clinical and radiographical parameters on chest radiography. MATERIALS AND
      METHODS: We retrospectively evaluated 242 consecutive patients that were admitted
      to our intensive care unit for dyspnea. Chest radiography was performed for all
      patients with the posteroanterior view. Cardiothoracic ratio (CTR), mediastinal
      ratio (MR), aortic width (AW) parameters and the grade of aortic calcification
      were recorded. Patients with grade 1, 2 or 3 were defined as the calcification
      positive (+) group and patients having no calcification (grade 0) were defined as
      the calcification-negative (-) group. Statistical analyses were performed on both
      groups. RESULTS: The study population consisted of 124 (51.2%) female and 118
      (48.8%) male patients. The mean age was 67 +/- 12 (range: 25-101) years. There
      was no significant relationship between aortic arch calcification and gender,
      presence of hypertension, diabetes mellitus, lipid levels, AW and MR, but age was
      correlated positively with aortic arch calcification with high statistical
      significance (p<0.0001). In patients with coronary artery disease (CAD), the
      prevalence of aortic arch calcification tended to be higher but was not
      statistically significant (p=0.07). The grade of calcification was not found to
      be correlated with gender, comorbidity, lipid levels, MR or CTR. However, as the
      grade of calcification increased, the mean age of patients in consecutive
      calcification grade groups tended to increase significantly. CTR, MR and AW
      increased with age. However, on regression analysis, only age was found to be an
      independent factor for aortic knob calcification (beta=0.397, t=6.375, p<0.0001).
      CONCLUSION: Simple, useful radiographical parameters such as AW, CTR, MR and
      calcification grade can help to predict the etiology of dyspnea and
      cardiovascular disease.

PMID- 25610048
TI  - Atlantodental osteoarthritis as a cause of upper cervical myelopathy: a case
      report.
AB  - Atlantoaxial instability frequently causes extrinsic cervical myelopathy via
      anterior displacement of the posterior arch of the atlas. However, upper cervical
      myelopathy resulting from atlantodental osteo-arthritis with the hypertrophic
      dens due to atlantoaxial instability is very rare. We present a case of upper
      cervical myelopathy secondary to atlantoaxial instability and atlantodental
      osteoarthritis. Although there was no atlantoaxial subluxation on the flexion and
      extension radiographies, hypertrophic changes of the anterior arch of the atlas
      with the dens axis and a fusion of the atlanto-dental joint resulting from
      atlantoaxial instability were determined on computed tomography and magnetic
      resonance imaging. 

PMID- 25610049
TI  - A new technique for laryngeal mask airway insertion in a newborn with pierre
      robin syndrome: a case report.
AB  - Babies with Pierre Robin syndrome have serious life-threatening risks because of
      acute respiratory distress and difficult airway management. It is difficult to
      perform endotracheal intubation in these babies for general anesthesia. We
      present successful insertion of laryngeal mask airway in a neonate with typical
      clinical features of Pierre-Robin syndrome using a size 1 laryngeal mask airway
      for a ventriculoperitoneal shunt operation. The patient had micrognathia,
      glossoptosis with cleft palate, and partial trismus. His mouth opening was
      restricted to 0.6 cm. Anesthesia was deepened with sevoflurane, maintaining
      spontaneous ventilation, but laryngoscopy was impossible because of the limited
      mouth opening. After unsuccessful attempts to insert an LMA by standard and
      rotational techniques, it was inserted using a novel modified rotational LMA
      insertion technique, which we have termed the 'squeezing technique'. 

PMID- 25610050
TI  - Isolated left ventricular noncompaction in children: two cases with different
      manifestations.
AB  - Isolated noncompaction of the ventricular myocardium is an uncommon disorder
      characterized by an excessively prominent trabecular meshwork seen in the early
      period of embryogenesis. The clinical presentation of noncompaction includes a
      high prevalence of heart failure, thromboembolic events and arrhythmias.
      Echocardiography is the procedure of choice for the diagnosis of noncompaction.
      We report two demonstrative patients with isolated noncompaction of the left
      ventricular myocardium and review the available related literature. 

PMID- 25610051
TI  - Repairing an achilles tendon rupture using the partial lindholm technique
      augmented by the plantaris tendon: a case report.
AB  - Many techniques have been described for the treatment of an acute achilles tendon
      rupture, but there is unfortunately no agreement between orthopedic surgeons
      regarding the best repair technique and post-treatment rehabilitation protocol.
      Overall, the surgical methods can be classified as either an open procedure or as
      a percutaneous procedure. While numerous techniques have been described for open
      surgical procedures, the strength of the repaired tendon, the healing time, the
      rerupture rates, and the changes in the range of motion due to adhesions may be
      the ultimate determining factors of the success of the procedure. In this case
      study, we report the results of treating a 35-year-old patient who suffered an
      achilles tendon rupture by combining two recently described surgical methods into
      a novel repair technique. 

PMID- 25610052
TI  - Blow-Out Fracture due to a Hazel Stick Beat.
AB  - The aim of this case report is to demonstrate that blow-out fractures can occur
      not only by a classical trauma mechanism but also from the consequences of a
      stick beat. A 66-year-old male was admitted to our hospital complaining of a
      sudden swelling of his right eyelid after blowing his nose. In his medical
      history there was the report of a hazel stick beat the previous day. Upon
      ophthalmological examination, ecchymosis was observed in the right orbital
      region, and subcutaneous amphisema in addition to a dense subconjunctival
      hemorrhage were detected. Using computed tomography (CT), the intraorbital air
      density in the soft tissues and the right maxillary sinus wall fracture
      possessing fluid density compatible with hemorrhage was observed. The patient was
      treated conservatively with prednisolone and antibiotics. We conclude that a blow
      out fracture may occur in patients who experience orbital trauma, even in cases
      of low-energy trauma. These patients may be symptomatic after an episode of hard
      nose-blowing. 

PMID- 25610053
TI  - Biliary stent migration with duodenal perforation.
AB  - Intestinal perforation from a migrated biliary stent is a known complication of
      endoscopic biliary stent placement. We present a case of stent migration and
      resultant duodenal perforation after stent placement for a malignant biliary
      stricture in a 52-year-old woman. We review the current literature on the
      diagnosis and management of stent migration and intestinal perforation after
      endoscopic stent placement for biliary strictures. A plain abdominal radiograph
      is necessary for early diagnosis of biliary stent migration. If a stent becomes
      lodged in the gastrointestinal tract, endoscopic or operative extraction of the
      stent is necessary to prevent subsequent intestinal perforation and peritonitis.
      Intestinal perforation secondary to biliary stent dislocation should be
      considered in all patients presenting with fever and abdominal pain after biliary
      stent insertion. Any abnormality that prevents stent migration through the
      intestinal tract such as gastroenterostomy, abdominal wall hernia, extensive
      adhesions or colonic divertucula may be a contraindication for insertion of a
      plastic biliary stent because of increased perforation risk. 

PMID- 25610054
TI  - Bone scintigraphy results in a patient with sapho syndrome.

PMID- 25610055
TI  - Serum sodium levels in sigmoid volvulus.
AB  - OBJECTIVE: Sigmoid volvulus (SV) is an uncommon type of large bowel obstruction.
      This study sought to determine serum sodium concentrations in patients with SV.
      MATERIALS AND METHODS: The records of 89 patients with SV and 40 patients with
      obstructive rectosigmoid cancer (ORC) were reviewed retrospectively. RESULTS: The
      mean serum sodium concentrations in patients with SV and in those with ORC were
      138.4+/-4.5 mEq/L and 137.7+/-3.2 mEq/L, respectively (t:0.7, P>0.05). The
      numbers of hyponatremic and hypernatremic patients were 13 vs. 4 and 1 vs. 0,
      respectively, in the SV and ORC groups (x2:0.5, P>0.05). CONCLUSION: No cause
      effect relationship was determined between serum sodium concentrations and SV.

PMID- 25610056
TI  - Comparison of 16-slice computed tomography with conventional angiography to
      evaluate coronary artery stent patency.
AB  - OBJECTIVE: In this study, we evaluated the utility of 16-slice MDCT
      (multidetector computed tomography) to assess stent patency after coronary artery
      stenting. MATERIALS AND METHODS: Retrospective ECG-gated CT-angiography using 16
      slice MDCT was performed in 52 consecutive patients with coronary artery stents.
      Qualitative assessment of 61 coronary stent lumens by MDCT is reported, and the
      reasons preventing assessment were investigated. RESULTS: All non-assessable
      stents were non-assessable due to partial volume effects and metal artifacts. To
      evaluate instent restenosis, conventional coronary angiography was performed on
      the 54 assessable stents in 48 patients, and the results were compared with the
      MDCT results. Based on the results of the conventional coronary angiography, MDCT
      correctly detected four in-stent restenosis. CONCLUSION: Despite some
      limitations, 16-slice MDCT provides sufficient evaluations of some coronary
      stents, and can detect in-stent restenosis with high accuracy.

PMID- 25610057
TI  - P53, bcl-2, ki-67 li (labeling index) status in benign, proliferative, and
      malignant ovarian surface epithelial neoplasms.
AB  - OBJECTIVE: Approximately 50% of human malignancies present with mutations in p53,
      which is the most common tumor suppressor gene involved with human malignancies.
      Bcl-2 is a protooncogene, and expression of its protein product is associated
      with a better prognosis in several malignancies. Ki-67 is a marker of cellular
      proliferation. The purpose of this study was to determine whether simultaneous
      detection of p53, bcl-2 and Ki-67 using immunohistochemical staining can be used
      as a diagnostic factor in the assessment of human ovarian epithelial tumors.
      MATERIALS AND METHODS: The study was performed on formalin-fixed, paraffin
      embedded tissue samples from 75 epithelial ovarian tumors, 15 serous
      cystadenomas, 15 mucinous cystadenomas, 5 borderline serous cystadenomas, 5
      borderline mucinous cystadenomas, 15 serous cystadenocarcinomas, 15 mucinous
      cystadenocarcinomas and 5 endometrioid carcinomas. Immunohistochemical staining
      was performed using monoclonal antibodies against p53, bcl-2, and Ki-67(MIB1).
      RESULTS: Anti-p53 reactivity was observed in 14 tumors, all of which were
      malignant tumors, and no reactivity was observed in borderline or benign tumors.
      Overexpression of bcl-2 was observed in 12 benign neoplasms (40%), 5 of which
      were borderline (50%), but was not observed in any of the malignant tumors. There
      was a statistically significantly higher level of Ki-67 LI positivity in the
      malignant tumors than in the benign and borderline tumors (p<0.005). CONCLUSION:
      These data show significant differences in the expression of these markers in
      ovarian tumors and suggest a possible role for these tumor-associated genes as
      supplemental tools in diagnostic pathology. Furthermore, our findings support the
      redesignation of low malignant potential tumors (current nomenclature) to benign
      ovarian carcinoma.

PMID- 25610058
TI  - Congenital cystic pulmonary malformations in children: our experience with 19
      patients.
AB  - PURPOSE: Congenital cystic pulmonary malformations (CPM) are rare anomalies. The
      purpose of this study was to present our experience with CPM patients who were
      surgically treated in our clinic and to discuss our findings along with those
      from the literature. MATERIALS AND METHODS: Surgical treatment was performed on
      19 patients under the age of 16 who were diagnosed with CPM in our clinic between
      January 1995 and December 2008. The diagnoses, ages, gender, symptoms, locations
      of the lesions, surgical method used, hospitalization times, complications, and
      the results of all patients were retrospectively evaluated. RESULTS: The
      distribution of diagnoses was as follows: bronchogenic cyst(s) (BC) - 5 patients;
      pulmonary sequestration (PS) - 6 patients; congenital lobar emphysema (CLE) - 4
      patients; congenital cystic adenomatoid malformation (CCAM) Type I - 3 patients,
      and PS and CCAM coexistence - 1 patient. All patients underwent resection. No
      operative mortality occurred. The mean postoperative hospitalization time of the
      patients was 6.9 days (range 4-17 days). CONSLUSION: CLE, CCAM, and PS may lead
      to life-threatening respiratory distress in infants. BC, CCAM, and PS, on the
      other hand, often progress with recurrent pneumonia in children and adults.
      Surgery is needed to improve severe symptoms, prevent fatal complications, and
      establish a histopathological diagnosis.

PMID- 25610059
TI  - The protective effect of dehydroepiandrosterone on ovarian tissues after torsion
      detorsion injury: a stereological and histopathological study.
AB  - OBJECTIVE: Ovarian torsion is a rare problem in pre-pubescent girls that must be
      included in the differential diagnosis of patients with abdominal or pelvic pain.
      Current advice for treatment to support ovary preservation considers the
      macroscopic appearance of the ovary, but this is not a reliable indicator of the
      degree of injury in cases of ovarian torsion. The aim of this study was to
      determine the effects of dehydroepiandrosterone (DHEA) treatment on the rat ovary
      after torsion-detorsion injury using a histopathological approach and
      stereological methods. MATERIALS AND METHODS: Fifteen adult female Sprague Dawley
      rats were divided into three groups: sham operated (Control; n=5), torsion
      detorsion with saline (Saline; n = 5), and torsion-detorsion with DHEA (DHEA; n =
      5). Rats in the sham-operated group underwent a surgical procedure similar to the
      other groups, but the adnexa were not torsioned. The DHEA group was injected
      intraperitoneally 3 hours before detorsion and saline was administered to the
      saline group. After 24 h of adnexal detorsion, the rats in all groups were
      sacrificed and the adnexa were removed. The volume of ovarian stroma and edema
      were estimated using the Cavalieri Principle and were applied to serial paraffin
      sections. Ovary sections were also evaluated histopathologically. RESULTS: The
      volume of ovarian edema was 35.4% lower in the saline group compared to the
      control group (p> 0.05). The volume of ovarian edema increased by 73.4% in the
      DHEA group (p<0.05). In the experimental groups, stromal volume was 41.0% higher
      in the saline group and 52% higher in the DHEA group in comparison to the control
      group. Statistically significant differences were found when comparing the volume
      of both ovarian edema and stroma between experimental groups (Detorsion/Saline
      group - Detorsion/DHEA group; p< 0.01). Histopathologically, mononuclear cell
      infiltration and vascular dilatation, perivascular edema and common necrotic
      changes were obvious in the torsion-detorsion damaged ovary. These changes were
      partially ameliorated by DHEA treatment. CONCLUSIONS: The present study shows
      that administration of DHEA has beneficial effects in the prevention of ischemia
      reperfusion injuries of the ovaries.

PMID- 25610060
TI  - Effect of positive lcm-igm on graft survival in living donor renal
      transplantation.
AB  - OBJECTIVE: Renal transplantation is an outstanding therapy for end-stage renal
      failure and has been shown to increase life expectancy and quality of life, while
      reducing medical expenditure. The presence of IgM antibodies in recipient serum
      is not a contraindication for renal transplantation. However, the presence of
      this antibody may have significant clinical implications. IgM autoantibodies have
      been blamed for a group of accelerated or hyperacute cases of graft rejection. In
      this study, graft and patient survival outcomes after renal transplantation in
      LCM IgM-positive recipients have been assessed. MATERIALS AND METHODS: Data from
      32 LCM IgM-positive kidney recipients who underwent renal transplantation at the
      Akdeniz University Transplantation Center between January 2006 and August 2008
      were assessed. RESULTS: The mean age was 34 +/- 13.5 (9-66). Twenty patients were
      male, and twelve were female. The mean length of therapy with dialysis was 22.94
      +/- 30.06 months (0-120). The duration of cold ischemia was 28.63 +/- 5.85
      minutes (21-42). CONCLUSION: Throughout the follow up period, the mean creatinine
      level was 1.3 mg/dL (0.69-4.5). Graft loss occurred in only one patient and was
      due to hemophagocytic syndrome and acute rejection. During follow up, creatinine
      elevation was seen in 12 patients (4%) in the early postoperative period. These
      patients were thought to have transplant rejection, and therapy for rejection was
      given. The therapy was successful. Graft survival was calculated to be 96 +/-
      3.5%, and none of the patients were lost.

PMID- 25610061
TI  - The relationship between genetic variations of the cholesteryl ester transfer
      protein gene and coronary artery disease in Turkish subjects.
AB  - OBJECTIVE: Although the relationship between cholesteryl ester transfer protein
      (CETP) and cholesterol metabolism has been characterized in recent years, the
      effect of CETP genetic variants associated with coronary artery disease (CAD) is
      still unclear. Therefore, we investigated the association between CETP gene
      polymorphism and levels of lipid in patients with CAD. MATERIALS AND METHODS: We
      conducted a case-control study that included 194 unrelated subjects who underwent
      coronary angiography for suspected ischemic heart disease. This group was divided
      into 96 patients with angiographically documented CAD and 98 subjects
      (individuals matched for age and gender) without angiographically documented CAD
      (CAD-free subjects), all of whom were studied to examine the genotypic
      distribution of the CETP gene polymorphism in CAD. Genotyping was performed via
      polymerase chain reaction. RESULTS: Of the 96 patients with CAD, 38 (40%) were
      B1B1, 42 (44%) B1B2 and 16 (16%) B2B2, compared with the control subjects, of
      which 35 (36%) were B1B1, 44 (45%) B1B2 and 19 (19%) B2B2. There were no
      significant differences between patients with CAD and control subjects in the
      distribution of the CETP gene polymorphism. Patients with the B1B1 genotype had
      lower high-density lipoprotein-cholesterol (HDL-C) and higher triglyceride (TG)
      levels than patients with the B2B2 genotype (p<0.05). In addition, among control
      subjects HDL-C levels were significantly higher in subjects with the B2B2
      genotype than in subjects with the B1B1 genotype (p<0.01). CONCLUSION: Our
      results suggest that genetic variations of the CTEP gene may be responsible for
      low HDL-C levels but may not be considered as a risk factor for CAD in the
      Turkish population.

PMID- 25610062
TI  - Imaging features of cervical lymphangiomas as a cause of respiratory distress and
      vascular-lymphatic disturbance.
AB  - OBJECTIVE: Our aim is to present the imaging features of cervical lymphangiomas,
      which may be related with respiratory and vascular disturbances. MATERIALS AND
      METHODS: Nine patients with cervical lymphangioma were evaluated with ultrasound
      (US), computed tomography (CT), and/or magnetic resonance imaging (MRI). While
      one case was a fetus in the second trimester, eight cases with tracheal stenosis
      were neonates or in childhood. RESULTS: One case was diagnosed in utero with US.
      All lymphangiomas were hypoechoic on the US and were of low-density (20-25 HU) on
      the CT. They showed a heterogeneous hypo- or hyperintense signal on T1-weighted
      MR images and a heterogeneous hyperintense signal on T2-weighted images. Upon
      contrast-enhanced CT and MR imaging, mild contrast enhancements were detected,
      particularly on the thick septations. CONSLUSION: Cervical lymphangiomas present
      as cystic lesions with septations, and they may cause respiratory distress or
      vascular-lymphatic disturbance.

PMID- 25610063
TI  - Effects of Lacidipine, Ramipril and Valsartan on Serum BNP Levels in Acute and
      Chronic Periods Following Isoproterenol-Induced Myocardial Infarction in Rats.
AB  - OBJECTIVE: Myocardial infarction (MI) as a result of cardiovascular disease is
      the principal cause of death in both developed and developing countries. Brain
      natriuretic peptide (BNP) is an important marker of cardiac failure.
      Cardioprotective activities of the antihypertensive drugs lacidipine (LAC),
      ramipril (RAM) and valsartan (VAL), against isoproterenol (ISO)-induced MI, have
      been determined. However, the levels of BNP, an indicator of left ventricular
      failure, have not been evaluated. MATERIALS AND METHODS: This study investigated
      the effects of LAC, RAM and VAL on serum BNP levels in acute and chronic periods
      after ISO-induced MI in rats. RESULTS: Serum BNP was found to be significantly
      increased in the acute MI model, but not in the chronic MI model. RAM and VAL
      application decreased BNP levels that had been increased after acute MI
      induction. Additionally, no significant differences were seen in chronic MI+drug
      groups compared with both intact and chronically infarcted control groups.
      CONCLUSION: The acute MI model, but not the chronic MI model, was associated with
      increased serum BNP levels. Pre-treatment with RAM and VAL, but not LAC,
      prevented the acute MI-induced increase in serum BNP levels, suggesting that
      inhibition of the renin-angiotensin system has prophylactic effects in the acute
      MI model. Therefore, both RAM and VAL may become first-line drugs for the
      treatment of hyper-tensive patients who are at high risk for cardiovascular
      failure.

PMID- 25610064
TI  - Hepatic hydatid disease: radiographics findings.
AB  - Hydatid disease (HD) is a unique parasitic disease that primarily affects the
      liver and is endemic in many parts of the world. There are four types of hydatid
      cysts (HCs) with various levels of organ involvement. All four HC types can be
      seen in the liver, with the right lobe being the most common site of involvement.
      There are many potential intrahepatic and extrahepatic complications that affect
      the liver and other organs. Intrahepatic complications include vascular and
      biliary complications and infection. With rare portal vein compression and
      decreased vascular supply, the involved lobe may show atrophic changes while the
      other lobe becomes hypertrophic. Intrahepatic biliary dilatation results from
      large cysts compressing intrahepatic ducts or due to cyst rupture into the
      biliary ducts. Cyst infection may also occur via a similar mechanism.
      Extrahepatic complications result from exophytic growth and hematogeneous
      dissemination. Exophytic growth causes migration of cysts into the lungs,
      mediastinum, heart and peritoneum. Hematogeneous dissemination involves all other
      organs. 

PMID- 25610065
TI  - Absence of the Left Main Coronary Artery: MDCT Coronary Angiographic Imaging.
AB  - Absent left main coronary artery (LMCA) is a rare congenital cardiac
      malformation. We present a case report of a 65-year-old woman with anomalous
      origin of the left anterior descending (LAD) and circumflex (LCx) artery
      separated from the left sinus of Valsalva that was diagnosed by multi-detector
      row computed tomography (MDCT) coronary angiography. Our case indicates that MDCT
      plays an important role in the diagnosis of some rare coronary anomalies. 

PMID- 25610066
TI  - A predisposing factor for spontaneous choledochal cyst perforation: esophageal
      dilatation procedures.
AB  - Cyst rupture is one of the rarest complications of choledochal cysts (CC). We
      report an 8-year-old boy with CC rupture leading to bile peritonitis following
      repeated esophageal dilatations for corrosive stricture, and discuss how the
      esophageal dilatation procedures might constitute a predisposing factor for CC
      perforation. 

PMID- 25610067
TI  - A Rare Variation of Hepatic Arteries (Michels Type IV): MDCT Angiographic
      Findings.
AB  - Recently, evaluation of hepatic artery variations has become increasingly
      important as liver transplantation from live donors gains in popular. Many
      diagnostic tools can be used to evaluate hepatic artery anatomy. Multi-detector
      computed tomography angiography (MDCTA) is one these methods. In this case
      report, we represent MDCTA findings of Michel type IV variation, which is a very
      rare condition of hepatic arteries. 

PMID- 25610068
TI  - Management of resistant cardiac depression after hepatic trauma controlled with a
      packing procedure.
AB  - In addition to hemorrhage, which is one of the most well-known factors, there are
      many other causative factors for serious hypotension after hepatic trauma. In
      this report, we present patients with persistent cardiac depression after
      perihepatic packing due to high grade liver injury and report on treatment
      modalities, including the early second-look procedure. Three patients with
      isolated hepatic trauma were included. Two of the patients who underwent
      perihepatic packing were transferred from outside hospitals, and one patient
      required repacking due to severe hemorrhage. All patients had grade IV injuries
      due to blunt (n=2) or penetrating injury (n=1). In the intensive care unit,
      central venous pressure (8, 12, 13 mmHg) and hematocrit (26, 27, 29%) were in the
      normal range, but blood pressure (40/60, 50/70, 45/75mmHg) was abnormal despite
      the use of inotropic support. The three patients underwent an unpacking procedure
      8, 10, and 14 hours later, respectively. Inotropic support was not required after
      postoperative hours 3, 5, and 6, respectively. The management of post reperfusion
      syndrome due to hepatic trauma can be achieved, but close collaboration between
      the surgeon and anesthesiologist is absolutely necessary. In the case of
      resistance cardiac depression in patients with packing, second-look procedures
      should be performed as early as possible. 

PMID- 25610069
TI  - Metastatic glucagonoma.
AB  - We report a case of a very rare endocrine tumor of the pancreas. The patient is a
      53-year-old female who has necrotizing and crusty maculopapular lesions on the
      upper and lower extremities and was diagnosed with bullous pemphigoid. The
      patient's symptoms included fatique and weight loss, and examination revealed
      pale sclera, angular chelitis and glossitis. Because the CA 19-9 and glucagon
      levels were high, and abdominal dynamic CT showed a mass in the pancreas body and
      metastatic lesions in the liver, the decision was made to operate. A distal
      pancreatectomy, splenectomy, cholecystectomy and right trisegmentectomy were
      performed. The histopathology of the tumor was reported as a neuroendocrine
      tumor, which was concordant with glucagonoma. The patient died on postoperative
      day 12 due to liver failure. According to the literature, when safe conditions
      were obtained, aggressive surgery followed by chemoterapy can increase the
      survival rate of these patients. 

PMID- 25610070
TI  - Cardiac hydatid cyst.

PMID- 25610071
TI  - Giant hepatic hemangioma.

PMID- 25610072
TI  - Benign nodular goiter causing upper airway obstruction.
AB  - OBJECTIVE: Benign nodular goiter (BNG) can cause narrowing of the upper airway.
      In some rare cases, obstruction of the upper airway also occurs. The following
      paper reports our experiences with regard to BNG patients who experienced
      obstruction of the upper airway. MATERIALS AND METHODS: We retrospectively
      investigated the records of 13 patients with acute airway obstruction due to BNG
      who were admitted to the General Surgery Department of Ataturk University Medical
      School between January 2000 and December 2007. RESULTS: Thirteen patients with
      airway obstruction secondary to BNG were hospitalized during this period. There
      were two males and 11 females, and the mean age was 58.5 years (range 37-74
      years). For all patients, the primary symptom upon admission was defined as
      respiratory distress; all patients had varying degrees of respiratory distress
      upon admission. Three of the patients underwent emergent endotracheal intubation
      in the emergency room. A preoperative radiological evaluation was performed with
      thyroid ultrasonography (US) and computed tomography (CT). There were
      retrosternal or substernal components of the BNG in nine patients. Twelve
      patients underwent operations, while one patient with mild respiratory distress
      elected not to be operated on. Ten patients underwent total thyroidectomies,
      while two patients underwent near-total thyroidectomies. One patient with
      retrosternal goiter also underwent a median sternotomy. Three patients received a
      tracheostomy after the operation. Suction drains were utilized in all operations.
      During the post-operative period, two patients suffered from voice impairment,
      and seven patients experienced hypocalcemia. Two patients died. Pathological
      examination of the thyroidectomy tissue revealed BNG in all cases. In addition,
      two patients had micropapillary carcinomas. CONCLUSION: Although BNG causing
      upper airway obstruction is rare, it is an important clinical entity because of
      the need for emergent operation, the increased rate of complications, and high
      mortality.

PMID- 25610073
TI  - Results of upper gastrointestinal system endoscopy in women with dyspeptic
      symptoms.
AB  - OBJECTIVE: In this study, the results of upper gastrointestinal system endoscopy
      in women with dyspeptic symptoms were evaluated retrospectively. MATERIALS AND
      METHODS: Two hundred thirty seven women with dyspeptic symptoms were evaluated
      with diagnostic endoscopy. An area from the oropharynx to the second part of the
      duodenum was inspected during endoscopic examination. RESULTS: The mean age of
      patients was 39.6+/-14.8 years. While the upper gastrointestinal system was
      totally normal in one patient, 538 pathologies were detected in the remaining 236
      patients. Mild to moderate insufficiency of the gastric cardia was seen in 124
      cases, while esophagitis was seen in 53, antral gastritis in 62, pangastritis in
      168, bulbitis in 23, erosive bulbitis in 22, duodenal ulcer in 28, and gastric
      ulcer in 30 patients. Both gastric and duodenal ulcers were seen in 6 patients.
      CONCLUSION: Esophagitis, pangastritis and peptic ulcers were detected more
      commonly in women with dyspeptic symptoms in this study when compared to women in
      the western part of Turkey. This difference may be due to environmental or
      dietary factors of this region.

PMID- 25610074
TI  - A stereological and electron microscopic study of the development of the nephron
      in prenatal and postnatal rats.
AB  - OBJECTIVE: To describe the morphometric and ultra-structural features of the
      kidney in fetal (20-day-old), newborn (7-day-old) and adult (180-day-old) rats.
      MATERIALS AND METHODS: Kidneys from all animals were excised, fixed in 3%
      glutaraldehyde in 0.1 M phosphate buffer, post-fixed in 1% phosphate-buffered
      osmium tetroxide, and examined by stereological and light and electron
      microscopic methods. RESULTS: Fetal kidneys displayed kidney corpuscles,
      glomeruli, and proximal and collective tubules at multiple developmental stages.
      Glomeruli in the outer surfaces of the kidney were less mature than those in the
      inner surface. Kidney corpuscles were made up of parietal cells and podocytes
      without feet. Kidneys from newborn rats were almost completely developed, while
      kidneys in adult rats were fully developed. Under stereological examination, the
      percent volume of cortex in fetal kidneys (86.19%) was higher than in newborn
      (53.77%) or adult rats (76.78%). Compared to both newborn and fetal rats, adult
      rats displayed the highest total volumes of distal and proximal tubules, but
      lower mean glomerular or Bowman's capsule volumes. On the other hand, the total
      number of glomeruli was increased in adult rats (32,600) as compared to newborn
      (17,896) and fetal (11,650) rats. CONCLUSION: These data suggest that development
      of metanephric kidneys is not yet complete by gestational day 20, but is almost
      complete at postnatal week one. Furthermore, the developmental stage of the
      kidney, as determined by stereology, correlates well with the age of the rat.

PMID- 25610075
TI  - Destructive effect of monopolar electrocautery knife usage on femoral artery
      endothelium during spine surgery: experimental study.
AB  - OBJECTIVE: Circulatory disorders are observed in the lower extremities of some
      patients after spinal surgery when a monopolar electrocautery knife (MEK) is
      used. Despite known the knowledge that electric currents can be hazardous to
      living tissues, MEK has been widely used in spine surgery. In this study, we
      investigated if MEK can cause endothelial injury in femoral arteries (FA).
      MATERIALS AND METHODS: Eighteen rabbits were included in this study, two of which
      were used as the reference group. The remaining animals were subjected to
      paravertebral soft tissue dissection along levels L1-L4. Half of the animals were
      dissected with MEK, and the other half were dissected with scissors and bipolar
      cautery. One month after the surgery, endothelial changes of the FAs were
      examined stereologically. RESULTS: Endothelial desquamation, cytoplasmic and
      nuclear condensations, cellular shrinkage and cellular loss were developed in the
      FAs of the MEK group. The endothelial cell density was 270 cells/mm2 in normal
      animals, 240 cells/mm2 in the non- MEK group and 190 cells/mm2 in the MEK group.
      The difference between the non-MEK and normal groups was not meaningful (P>0.05).
      The difference between the MEK and non-MEK groups was statistically significant
      (P<0.05); differences between the MEK and normal animals were even more
      significant (P<0.001). CONCLUSION: Sharp dissection with MEK can have a
      detrimental effect on the endothelial cells of the FAs and cause postoperative
      circulatory disorders in the lower extremities. Therefore, long-term high-voltage
      electrocauterization should be avoided during spinal surgery unless absolutely
      necessary.

PMID- 25610076
TI  - Hemolytic activities of the Candida species in liquid medium.
AB  - OBJECTIVE: The aim of this study was to evaluate the in vitro hemolytic
      activities of 107 Candida strains isolated from different clinical samples in
      liquid medium, and to examine the impact of glucose on this activity. MATERIALS
      AND METHODS: A total of 107 Candida isolates representing seven species (C.
      albicans, n=28; C. glabrata, n=23; C. tropicalis, n=17; C. parapsilosis, n=16; C.
      kefyr, n=14; C. krusei, n=5; C. guilliermondii, n=4) were included in the study.
      The hemolytic activities of the strains were tested on two different Sabouraud
      dextrose liquid media (SDB) containing 7% defibrinated human blood, one of which
      is supplemented with 3% glucose and the other without glucose. Cultures were
      evaluated at the end of a 48-hour incubation. The hemolysis in the media was
      detected spectrophotometrically by measuring the amount of released hemoglobin
      and compared with a standard hemolysate which was prepared prior to testing. The
      degree of hemolysis (percentage value) by an individual strain was calculated
      according to the following formula below: (Absorbance of supernatant media at 540
      nm / Absorbance of standard hemolysate at 540 nm X 100). RESULTS: In the liquid
      medium without glucose, strains generally produced hemolysis at low levels. The
      degree of hemolysis produced by all species increased noticeably in the liquid
      medium with glucose. Strains of C. albicans and C.kefyr had demonstrated
      significant hemolytic activity, whereas others had lower activity. C.
      parapsilosis exerted very little hemolytic activity in the medium with glucose
      and showed no activity in the medium without glucose. CONCLUSION: The hemolytic
      activities of most Candida species was found to be higher in the human blood
      enriched SDB medium containing 3% additive glucose than in the one free from
      additives. This result indicates that increased blood glucose concentration may
      contribute to increased hemolytic activity in Candida species, and it suggests a
      parallel with possible pathogenesis of Candida in patients with diabetes
      mellitus.

PMID- 25610077
TI  - A novel application for the cavalieri principle: a stereological and
      methodological study.
AB  - OBJECTIVE: The Cavalieri principle was applied to consecutive pathology sections
      that were photographed at the same magnification and used to estimate tissue
      volumes via superimposing a point counting grid on these images. The goal of this
      study was to perform the Cavalieri method quickly and practically. MATERIALS AND
      METHODS: In this study, 10 adult female Sprague Dawley rats were used. Brain
      tissue was removed and sampled both systematically and randomly. Brain volumes
      were estimated using two different methods. First, all brain slices were scanned
      with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor.
      Brain volume was then calculated based on these images. Second, all brain slices
      were photographed in 10* magnification with a microscope camera, and brain
      volumes were estimated based on these micrographs. RESULTS: There was no
      statistically significant difference between the volume measurements of the two
      techniques (P>0.05; Paired Samples t Test). CONCLUSION: This study demonstrates
      that personal computer scanning of serial tissue sections allows for easy and
      reliable volume determination based on the Cavalieri method.

PMID- 25610078
TI  - Assesment of protein gene product (pgp9.5) enzyme activity against potential
      Peptide substrate.
AB  - OBJECTIVE: PGP9.5 is a human neuron specific ubiquitin carboxyl-terminal hydolase
      that has been shown by immunuhistochemistry to be present selectively in
      ubiquitinated inclusions in chronic human degenerative disease. Paraffin sections
      known to contain ubiquitinprotein conjugate immunureactivity in neurofibrillary
      tangles (NFT), cortical Lewy bodies, Rosenthal fibres and in Pick bodies were
      immunostained with PGP9.5. In Alzheimer's disease loosely arranged globose-type
      neurofibrillary tangles (NFTs) were immunostained together with neuritis
      surrounding senile plaques (SP). While PGP9.5 has been demonstrated to have
      ubiquitin carboxy-terminal ethyl esterase activity, there has not been clear
      identification of its substrate specificity. The main aim was, therefore, to
      purify PGP9.5 and study its carboxyl-terminal hydrolase activity using, as
      substrates, synthetic peptides that were chosen to reflect the known possible
      functions of the enzyme. MATERIALS AND METHODS: Ubiquitin is cleaved from
      conjugates by ubiquitin carboxyl-terminal hydrolases, one of which is protein
      gene product 9.5 (PGP 9.5). PGP9.5 was purified to homogeneity from human post
      mortem brain tissue, its identity confirmed by protein sequence determination.
      Potential peptide substrates were incubated with PGP 9.5 and assayed by HPLC.
      RESULTS: Overlap region of ubiquitin in branched gene products were not
      substrates. Evidence was obtained for cleavage of linearly-conjugated
      polyubiquitin. CONCLUSION: Degradation of abnormal proteins by ubiquitin system
      depends on binding structure of ubiquitins. It has been shown that only linear
      ubiquitis are substrate for the PGP 9.5. The importance of it is not well
      understood.

PMID- 25610079
TI  - The predictive value of routine preoperative laboratory parameters in patients
      with sporadic and solitary parathyroid adenoma.
AB  - OBJECTIVE: Primary hyperparathyroidism (pHPT) is a disease in which the diagnosis
      depends increasingly on laboratory tests since the majority of patients are
      elderly people without typical symptoms. The aim of this study was to calculate
      the specificity and sensitivity rates, and positive predictive value of blood Ca,
      P, ALP, and iPTH levels in patients with PA. MATERIALS AND METHODS: We calculated
      the specificity and sensitivity rates, and positive predictive value of blood
      calcium (Ca), phosphorous (P), alkaline phosphatase (ALP), and intact
      parathormone (iPTH) levels in patients with sporadic and solitary parathyroid
      adenoma (PA). RESULTS: Twenty six patients with PA were included in the study.
      The mean age was 44.5+/-14.9 (18-70) years. Blood levels of Ca, P, ALP, and iPTH
      were 2.5+/-0.3 mmol/L, 0.8+/-0.3 mmol/L, 21.4+/-31.5 MUkat/L, and 518.0+/-633.4
      ng/L, respectively. With respect to the diagnosis of pHPT, the sensitivity of
      blood levels of iPTH, P, Ca, and ALP were 96%, 94%, 81%, and 73%, respectively.
      The specificity and positive predictive value of all parameters were 100% for the
      diagnosis of PA. CONCLUSION: Routine laboratory parameters are specific and
      predictive for pHPT. However, the sensitivities of P and iPTH are higher than
      those other parameters.

PMID- 25610080
TI  - The effects of zinc sulfate on the levels of some elements and oxidative stress
      occurring in lenses of rats exposed to total cranium radiotherapy.
AB  - OBJECTIVE: There is currently substantial clinical interest in zinc (Zn) as an
      antioxidant and a protective agent against radiation-related normal tissue
      injury. To further assess the potential antioxidative effects, the effects of Zn
      were studied in rat lenses, a model of radiation-induced oxidative stress.
      MATERIALS AND METHODS: Sprague-Dawley rats were divided into three equal groups.
      Group 1 received neither Zn nor irradiation (control group). Group 2 (RT group)
      and 3 (RT+Zn group) were exposed to total cranium irradiation of 5 Gy in a single
      dose by using a cobalt-60 teletherapy unit. In addition to irradiation, group 3
      was administered 10 mg/kg/day Zn. At the end of 10 days, the rats were killed.
      Their eyes were enucleated to measure the activities of antioxidant enzymes and
      the levels of iron, calcium, sodium and potassium. RESULTS: Irradiation
      significantly increased malondialdehyde levels as an end product of lipid
      peroxidation, glutathione peroxidase activity, and iron and calcium
      concentrations. Irradiation decreased super-oxide dismutase activities and zinc
      concentrations in the rat lens, indicating an increased oxidative stress
      generated by the decomposition of water and/or Fenton reaction. Malondialdehyde
      levels and iron and calcium concentrations were significantly decreased, and
      superoxide dismutase and glutathione peroxidase activities and zinc
      concentrations were increased, in the rat lenses of the RT+Zn group. No
      differences were detected in any final measurement of sodium and potassium in the
      direct comparison among all groups. CONCLUSION: Zinc, acting as an antioxidant
      agent, may protect the lens from radiation-induced injury by improving oxidative
      stress generated by the decomposition of water and/or Fenton reaction.

PMID- 25610081
TI  - Ileosigmoid knotting.
AB  - Ileosigmoid knotting (ISK) is the wrapping of the ileum around the sigmoid colon
      and its mesentery or vice-versa. The incidence of ISK is not well known, but it
      generally occurs in areas with a high incidence of sigmoid volvulus, and it is
      common in adult males. The etiology of ISK is controversial. The main symptoms
      are abdominal pain, distention, obstipation, and vomiting, while the main signs
      are abdominal distention and tenderness. There are no specific blood tests for
      diagnosing ISK. Plain abdominal X-ray radiographs demonstrate a dilated sigmoid
      colon and multiple small intestinal air-fluid levels. Abdominal CT demonstrates a
      twisted and dilated sigmoid colon with whirled sigmoid mesentery, in addition to
      twisted and dilated small intestinal segments. The accurate preoperative
      diagnosis of ISK is difficult. After rapid and prompt resuscitation, emergency
      surgery is needed in the treatment of ISK. In gangrenous cases, resection with
      primary anastomosis is preferred, while, in nongangrenous cases, untying of the
      knot may be performed as a sole surgical procedure, or a volvulus-preventing
      procedure may be added. The mean mortality rate for ISK is 6.8-8% in
      nongangrenous and 20-100% in gangrenous cases. 

PMID- 25610082
TI  - The efficacy and safety of extracorporeal shock wave lithotripsy in children.
AB  - Technological advances in the design of shock wave lithotriptors have
      precipitated important changes in the management of urolithiasis in children. New
      generation lithotriptors have reduced the need for anesthesia, lowered
      hospitalization duration, and resulted in better fluoroscopic targeting reducing
      radiation exposure. Currently, shock wave lithotripsy (SWL) has become standard
      first line treatment for most renal and ureteral calculi in children. Herein, the
      literature and assess success rates, re-treatment rates, preoperative stenting,
      anesthesia requirements, side effects, and complications of SWL were reviewed. As
      a result, we aimed to demonstrate that SWL is safe for the treatment of pediatric
      urolithiasis. 

PMID- 25610083
TI  - Munchausen's Syndrome.
AB  - Although the differential diagnosis of hemoptysis is extensive, consideration of
      a factitious cause is rarely contemplated. Factitious hemoptysis is uncommon in
      children. We report a dramatic case of factitious hemoptysis in a 12-year-old
      girl. The features of Munchausen's syndrome are also reviewed. 

PMID- 25610084
TI  - Solid pseudopapillary tumor of the pancreas.
AB  - Solid pseudopapillary tumors of the pancreas, known as Frantz tumors, are rare
      pancreatic tumors that occur predominantly in women, with very few cases reported
      in men. We present the case of a 27-year-old female patient who came to the
      emergency room with an intense upper abdominal pain associated with nausea and
      vomiting and a palpable mass in the left upper quadrant. She was initially
      diagnosed with a post-traumatic pancreatic pseudocyst. The patient underwent
      distal pancreatectomy with splenic preservation; the histopathological report
      showed a pseudopapillary solid tumor of the pancreas without malignant cells. In
      this report, a case of rare solid-pseudopapillary tumor of the pancreas is
      described. Our objective was to report an infrequent case of pancreatic
      pseudopapillary tumor and to carry out a review of the literature. 

PMID- 25610085
TI  - Mitral valvular cyst mimicking a solid mass: misdiagnosis with imaging
      modalities.
AB  - This report describes a mitral valvular cyst mimicking a solid mass in an 80-year
      old patient. The diagnosis was based on histopathological evaluation of the
      resected material. This report emphasizes the possibility of misdiagnosis by
      echocardiographic and other imaging modalities of a mitral valvular mass in a
      patient without any clinical signs and symptoms. 

PMID- 25610086
TI  - Tracheal Rupture due to Diffusion of Nitrous Oxide to Cuff of High-Volume, Low
      Pressure Intubation Tube.
AB  - Tracheal rupture is a rare complication of endotracheal intubation. Risk factors
      include short neck, repeated attempts due to failed intubation, inappropriate
      stylus, over-inflation of the cuff, poor positioning of the tube, inappropriate
      tube size, weakened membrane structure due to steroid use, chronic obstructive
      pulmonary disease, tracheomalacia, kyphosis, and use of nitric oxide during the
      operation. In this article, we suggest that high-volume, low-pressure tubes may
      not always provide a low-pressure effect and could rupture due to reduced
      tracheal perfusion pressure and ischemic damage upon over-inflation. 

PMID- 25610087
TI  - Fusion of the rib on plain chest radiography: a real or false image?

PMID- 25610088
TI  - Hemangioma of the Parotid Gland in an Infant: MR and Doppler US Findings.

PMID- 25610090
TI  - Serum potassium levels in sigmoid volvulus.
AB  - OBJECTIVE: This study aimed to determine the serum potassium concentrations in
      patients with sigmoid volvulus (SV), which is a rare large bowel obstruction.
      MATERIALS AND METHODS: The records of 86 patients with SV were reviewed
      retrospectively, while the records of 41 patients diagnosed with obstructive
      rectosigmoid cancer (ORC) were considered as the control group and as such,
      served as a source for comparison. RESULTS: The analysis revealed a mean serum
      potassium concentration of 3.9 +/- 0.6 mEq/L for the patients with SV, while the
      mean potassium concentration was 3.9 +/- 0.5 mEq/L for the patients diagnosed
      with ORC (t:0.1, P>0.05). The number of hypokalemic and hyperkalemic patients
      identified in this study sample were 11 versus 5 patients and 1 versus 0
      patients, respectively for the SV and ORC groups (x(2) = 0.1 and 0.5,
      respectively with a P>0.05). CONCLUSIONS: No cause-and-effect relationship was
      observed between the serum potassium concentrations and SV. The serum potassium
      concentration is not pathognomonic for SV.

PMID- 25610091
TI  - The Association of HLA Class I and II Antigens in Teenagers with Caries
      Experience.
AB  - OBJECTIVE: There have been reports of a relationship between human
      histocompatibility antigen types and increased incidence of dental caries. The
      association between specific patterns of HLA genetic inheritance is not clear and
      not well studied. The aim of the study was to investigate the relationship
      between MHC alleles and DMFT index in 65 teenagers. MATERIALS AND METHODS: Sixty
      five teenagers were recruited from the students of elementary school of the
      university campus and the patients of the Ataturk University Dental School
      hospital. Low-resolution typing for the HLA-A, B, C and HLA-DR/DQ were performed
      by PCR-SSP method using SSP HLA class I generic DNA Typing Tray. RESULTS: The
      results showed that HLA-DRB1*04 and -DRB1*07 frequencies were significantly
      higher (30.4% and 26.08% respectively) in DMFT>=1 group as compared with DMFT:0
      group (10.5% and 5.26%), (p:0.168, OR:3.719; p:0.117, OR:6.353). Although
      frequencies of HLA-A*2, -B*27 and -B*51 alleles were increased in DMFT>=1 group,
      they were not statically important. HLA-DRB1*11 were found to be more common in
      DMFT: 0 groups. CONCLUSIONS: The pathogens involve in caries induce immune
      systems and response via the given HLA alleles could be important.

PMID- 25610092
TI  - The effects of adding various doses of clonidine to ropivacaine in spinal
      anesthesia.
AB  - OBJECTIVE: In this study, we compared the clinical effects of combined doses of
      ropivacaine and clonidine. MATERIALS AND METHODS: Seventy-five patients between
      ages 18 and 75, in ASA I-III groups who were to undergo elective lower extremity
      surgery, were included in the study with informed consent. Subjects were randomly
      assigned to 3 groups. Group I: % 1 ropivacaine 12 mg, group II: % 1 ropivacaine
      12 mg + clonidine 15 ug, group III: % 1 ropivacaine 12 mg + clonidine 30 ug. Mean
      arterial pressure, breathing, heart rate and peripheral oxygen saturation, total
      amount of ephedrine and atropine used, sensory and motor block levels, level of
      sedation, pain level and complications were monitored. RESULTS: The mean arterial
      pressure recorded in group III decreased significantly at 75, 105 and 120 min
      compared to groups I and II. In group I, time to two segment regression and time
      to sensory block to S2 was shorter when compared to the other groups (P<0.0001).
      The time to voiding and the duration of motor blockade was significantly longer
      in group I in comparison to the other groups. The need for atropine in group III
      was significantly higher (P<0.001). The incidence of hypotension and the
      requirement for ephedrine were significantly higher in groups II and III as
      compared to group I (P<0.01). Similarly, sedation in group III was significantly
      higher compared to the other groups (P<0.05). CONCLUSION: In summary, our study
      revealed that clonidine can be added to ropivacaine for spinal anesthesia in
      surgical interventions to obtain deeper and longer sensory and motor block.
      However, hypotension, bradycardia and sedation should be monitored closely.

PMID- 25610093
TI  - Celiac disease in childhood: evaluation of 140 patients.
AB  - OBJECTIVE: Celiac disease (CD) is a lifelong gluten-sensitive intestinal
      enteropathy that is multifactorial in its etiology. In the present study, we
      evaluated basic anthropometric, clinical, laboratory, and histological features
      of 140 Turkish children with CD. We particularly underscored the association of
      CD with other autoimmune diseases. MATERIALS AND METHODS: During the period from
      1999 to 2005, CD was diagnosed in 140 children according to ESPGAN criteria. The
      age, gender, clinical findings, hematological, and biochemical parameters at
      diagnosis were noted. Symptoms and signs were recorded. Endoscopic intestinal
      biopsies were taken from all children. RESULTS: Of the 140 children with CD, 75
      (53.6%) were female, and 65 (46.4%) were male. Mean age was 8.56 +/- 4.43 years
      (range 13 months to 18 years). The most frequent symptom was failure to thrive
      (81.4%), followed by chronic diarrhea (60%). Of the children with CD, nine (6.4%)
      had type 1 diabetes mellitus (DM), six (4.3%) had familial Mediterranean fever,
      three (2.1%) had alopecia areata, three (2.1%) had vitiligo, three (2.1%) had
      Down syndrome, two (1.4%) had lung tuberculosis, two (1.4 %) had autoimmune
      hepatitis, two (1.4%) had growth hormone deficiency, one (0.7%) had osteogenesis
      imperfecta, and one (0.7%) had Floating Harbor Syndrome. Elevated serum levels of
      ALT, CK and AST were detected in 48(34.8%), 50 (38.2%) and 67 (48.6%) children,
      respectively. CONCLUSION: The spectrum of clinical findings is very wide. In
      order to avoid overlooking CD in patients with extra intestinal symptoms and
      signs, physicians, especially pediatricians, should be informed about new
      atypical manifestations of CD.

PMID- 25610094
TI  - Irritable bowel syndrome and chronic gastritis, hemorrhoid, urolithiasis.
AB  - OBJECTIVE: Approximately 10-20% of the general population has irritable bowel
      syndrome (IBS), and IBS patients usually suffer from chronic gastritis (CG),
      hemorrhoids (H), and urolithiasis (U). MATERIAL AND METHODS: We randomly chose
      consecutive patients with upper abdominal discomfort. All possible causes of IBS
      including celiac sprue, giardiasis, lactose intolerance, and cholelithiasis were
      investigated. U was diagnosed either by medical history or as a result of
      laboratory findings. RESULTS: IBS patients (51) and patients without IBS (70)
      were studied. CG was diagnosed in 78.4% (40) of IBS cases, whereas this ratio was
      50.0% (35) in cases without IBS (p<0.001). Similarly, H was detected in 33.3%
      (17) of IBS cases, but it was only detected in 15.7% (11) of cases without IBS
      (p<0.05). Additionally, U was detected in 17.6% (9) of IBS cases and in 5.7% (4)
      of cases without IBS (p<0.05). CONCLUSION: Relationships between IBS and CG, H,
      and U are significant. IBS is a cascade of many physiologic events that is
      initiated by infection, inflammation, and psychological disturbances like many
      stresses, and this eventually terminates with gut dysfunction. Gastric acid is
      probably not involved in the etiology of IBS, but psychological factors also seem
      to be important in CG. The significant association between CG and IBS also
      support this hypothesis. Therefore, we believe CG is one of terminating points of
      the physiologic cascade of events in IBS. Bearing these associations in mind will
      be helpful during prevention, treatment, and follow up of these disorders,
      especially in internal medicine, urology, and general surgery polyclinics and
      primary health centers.

PMID- 25610096
TI  - The Levels of Serum C-Reactive Protein, Beta 2 Microglobulin, Ferritin, Lactate
      Dehydrogenase and Some Specific Proteins in Patients with Non-Hodgkin's Lymphoma
      Before and After Treatment.
AB  - OBJECTIVE: The aim of this study was to measure serum C reactive protein, beta2
      microglobulin, ferritin, lactate dehydrogenase, complement 3, complement 4,
      immunoglobulin A, immunoglobulin M, immunoglobulin G and transferrin levels in
      patients with Non-Hodgkin Lymphoma before and after treatment, and to determine
      whether any differences occur with treatment, investigate relationship between
      these parameters and systemic symptoms, and to determine whether they could be
      used as tumor markers. MATERIALS AND METHODS: The parameters listed above were
      studied before and after treatment in sera of 27 patients with the diagnosis of
      Non-Hodgkin Lymphoma who admitted to our department. Of the patients, 10 (37%)
      were females and 17 (63%) were males. Mean age was 57.7 +/- 16.5 (19-82) years.
      The subjects were newly diagnosed and treatment. RESULTS: Post-treatment serum
      ferritin and CRP levels were found to be significantly decreased in patients with
      NHL compared to pre-treatment levels (p=0.009 and p=0.015, respectively). In
      addition, ferritin levels measured before treatment were significantly lower in
      subjects with B symptoms than those without B symptoms (p=0.02). IgA levels of
      patients with B symptom were significantly increased compared to those without B
      symptoms following treatment (p=0.03). CONCLUSIONS: We are in the opinion that
      serum ferritin and CRP parameters may be used as tumor markers and may be
      indicators in the efficacy evaluation of treatment in Non-Hodgkin's Lymphoma.

PMID- 25610095
TI  - HLA Antigen Profile Differences in Patients with SCC (Squamous Cell Carcinoma) In
      Situ /Actinic Keratosis and Invasive SCC: Is There a Genetic Succeptibility for
      Invasive SCC Development?
AB  - OBJECTIVE: Actinic keratoses (AK) are proliferation of neoplastic keratinocytes
      confined to the epidermis induced by damaging solar ultraviolet radiation (UVR).
      When the neoplastic keratinocytes extend in to papillary-reticular dermis, then
      the lesion termed as squamous cell carcinoma (SCC). We have compared HLA class I
      and II antigen profiles in three patient groups namely: AK (n: 31) (patients
      without past or present invasive SCC), invasive SCC (n: 38), and SCC derived from
      / inconjuction with AK (n: 11). MATERIALS AND METHODS: Low-resolution typing for
      the HLA-A, B, C and HLA-DR/DQ was performed by means of the PCR-sequence specific
      primer (PCR-SSP) method using SSP HLA class I generic DNA Typing Tray. RESULTS:
      HLA results of these three groups were compared with the healthy control group
      (n: 100). There were not significant difference in HLA class I and II antigen
      profiles in AK group compared to the control. Whereas HLA-A2 allele (60.52%,
      p=0.016, OR=2.726, 95%CI=1.265-5.876), HLA-B60 (13.15%, p=0.025, OR=7.424,
      95%CI=1.375-40.099) were higher in SCC group than the control. HLA-B51 allele
      (72.72%, p=0.008, OR=6.853, 95%CI=1.696-27.720) distribution were more common in
      SCC derived from AK than the control. CONCLUSIONS: Historically, AKs have been
      characterized as premalignant. It has, however, been considered that AK and SCC
      represent the same disease process at the different stages of evaluation.
      Clinically, and histopathologically it is difficult to determine where AK ends
      and invasive SCC begins. From dermatopathological point of view AK is clearly SCC
      in-situ, however although AK is a common lesion in Caucasians, not all AKs
      develop in to invasive SCC, at least not with the same biological pace. We
      concluded that genetic differences such as HLA class I and II distribution
      between AK and SCC may not seem to play susceptibility role for invasive SCC
      development.

PMID- 25610097
TI  - Neuroprotective effects of methylprednisolone and hypothermia after experimental
      spinal cord injury: a histopathological and stereological study.
AB  - OBJECTIVE: Spinal cord injury is a common trauma among severe accidents in which
      the spinal cord has been severed; intravenous methylprednisolone and hypothermia
      are widely used in the treatment of traumatic spinal cord injuries. However, no
      common consensus has been reached on therapeutic approaches to prevent and reduce
      disability caused by spinal cord injuries. In this study, the efficacy of
      methylprednisolone and hypothermia treatments after experimental spinal cord
      injury made by dynamic weight-drop model in rabbits was investigated. MATERIALS
      AND METHODS: This experiment consists of three groups: injured,
      methylprednisolone-treated and hypothermia-treated groups. The methylprednisolone
      treated group received intravenous methylprednisolone (30 mg/kg/day) immediately
      after spinal cord injury for three days. In the hypothermia-treated group, cold
      isotonic saline (5 degrees C) was infused via a cannula into the epidural space
      at a rate of 10 ml/min. The temperature of the tissue was allowed to reach 25oC,
      and then isotonic saline solution was given at a rate of 5 ml/min for 3 hours.
      Saline was given to the injured group following spinal cord injury. After 1 week
      of experimental injury, mid-thoracic level tissue was removed from the spinal
      cord for histopathological evaluation and subsequent stereological analysis.
      RESULTS: The volume of spinal cord segment, not only parenchyma of grey and white
      matter but also cavity, was estimated by the Cavalieri principle. Significant
      differences were seen between the injured group and methylprednisolone
      /hypothermia-treated groups in terms of the total volume cavity of spinal cord
      segment; cavity volume in the grey matter and cavity volume in the white matter.
      No significant differences were seen between methylprednisolone and hypothermia
      treated groups in terms of the total volume cavity of spinal cord segment; cavity
      volume in the grey matter and cavity volume in the white matter. CONCLUSIONS:
      These results suggested that both methylprednisolone and hypothermia treatment
      are neuroprotective in preventing spinal cord tissue from tissue damage after
      experimental injury.

PMID- 25610098
TI  - A simple, safe and effective approach to prevent postdural puncture headache:
      epidural saline injection.
AB  - OBJECTIVE: In this study, we investigated the safety and effectiveness of
      epidural saline injection to prevent post-dural puncture headache (PDPH) in
      patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Thirty
      three patients with ALL undergoing induction therapy were accepted for the study.
      Four to six courses of intrathecal methotrexate therapy were administered to each
      patient for central nervous system prophylaxis. Patients were divided into two
      groups. Lumbar puncture (LP) was performed without any additional intervention in
      the first group (18 cases), whereas 20 mL of isotonic saline was injected into
      the epidural space in the second group (15 cases). The frequency and severity of
      PDPH were compared between the two groups. RESULTS: Thirteen patients from the
      first group and five patients from the second group experienced at least one PDPH
      episode. In total, 54 PDPH episodes were reported in both groups. The rate of
      headache due to the LP was significantly higher in the first group than in the
      second group (48.8% vs. 16.4%, p<0.001). On the other hand, the severity of pain
      was also significantly higher in the first group (mean pain scores were 5.6 +/-
      1.62 vs. 3.07 +/- 1.18, p<0.001). Furthermore, two patients from the first group
      (11.11%) developed generalized convulsion attacks, and one of those patients
      experienced pulmonary arrest necessitating respiratory support. No serious
      complications were observed in the second group. CONCLUSIONS: Our study shows
      that isotonic saline injection into the epidural space after LP is a safe and
      effective approach to prevent PDPH and related complications.

PMID- 25610101
TI  - Aural Myiasis by Wohlfahrtia magnifica: Case Report.
AB  - A 5-year-old child living in Erzurum, Turkey, complaining of otalgia, otorrhea
      and pruritus in the right ear for three days, was examined. Otoscopic examination
      at the Department of Otorhinolaryngology revealed live maggots in the external
      auditory canal. Ten maggots were recovered and were identified as third stage
      larvae of Wohlfahrtia magnifica (Diptera: Sarcophagidae). Local and systemic
      antibiotic therapies were applied. No pathological findings were present at the
      follow-up examination after 15 days of therapy. 

PMID- 25610099
TI  - Mycophenolate mofetil in the treatment of systemic lupus erythematosus.
AB  - Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to
      be effective in transplant patients. It is also efficacious in the management of
      lupus nephritis and useful in the treatment of autoimmune conditions because its
      mechanisms of action target T- and B- lymphocytes, leading to suppression of the
      cell-mediated immune response and antibody formation. MMF has been used
      successfully to treat immune-mediated conditions like myasthenia gravis,
      autoimmune hepatitis and immune cytopenias. However, the conditions for its
      optimal use for non-renal manifestations (e.g., hematological, neuropsychiatric,
      myocardial, pulmonary or cutaneous symptoms) in lupus patients are unclear. There
      have yet to be any randomized, controlled trials to guide the optimal dose and
      duration of MMF treatment in such situations. MMF is well tolerated and safe to
      use, although there are reports of serious adverse effects including urticaria,
      myopathy, Epstein-Barr virus-associated B-cell lymphoma, cytomegalovirus
      infection and disseminated varicella zoster infection. Immunosuppressive
      treatment with MMF and supportive care over the past few decades have led to
      improved clinical outcomes in patients with severe lupus nephritis. A favorable
      long-term prognosis can be ensured provided that effective treatment is
      instituted early, before irreversible renal parenchymal damage occurs. Another
      area of concern for patients is the increased cost of long-term MMF use. 

PMID- 25610100
TI  - Malignant pleural effusions: appropriate treatment approaches.
AB  - Malignant pleural effusion (MPE) is a common and important clinical condition. A
      complication in many types of tumors, its presence indicates the onset of the
      terminal stages of cancer. Dyspnea is the most common symptom of MPE. The most
      common underlying tumors are lymphomas and cancers of the lung, breast and
      ovaries, which account for 75% of cases. The diagnosis of MPE can be established
      by the presence of malignant cells in the pleural fluid or tissue. Median
      survival in these patients ranges from 3 to 12 months, with the shortest survival
      period presenting in lung cancer patients. The aim of MPE therapeutic approaches
      should be effective treatment and a short hospital stay. There are many different
      treatment options for patients who suffer from MPE, including serial
      thoracentesis, tube thoracostomy, pleurodesis, long term pleural catheter,
      pleuroperitoneal shunt, decortication, chemotherapy and radiotherapy. The choice
      of therapy is determined based on a patient's clinical situation as well as the
      underlying disease. Today, intercostal tube insertion and chemical pleurodesis
      are the most commonly prescribed treatment modalities. 

PMID- 25610102
TI  - Central serous chorioretinopathy associated with rowatinex usage.
AB  - Central serous chorioretinopathy (CSC) is an idiopathic disorder characterized by
      serous detachment of the neurosensory retina. This report describes a case of CSC
      associated with rowatinex usage. 

PMID- 25610103
TI  - A Case Report of a Renal Transplant Patient with Progressive Neurological
      Disorder due to Tacrolimus.
AB  - Neurological complications of tacrolimus are usually mild (tremors, paresthesia,
      myalgia), however, serious complications that result in encephalopathy,
      convulsions and coma can be seen. Serious complications are more frequently
      reported following liver transplants and lungs transplants than renal transplants
      and are typically seen when tacrolimus concentrations exceed the 15 ng/L
      therapeutic limit. In this article we presented our case of a renal allograft
      receiver with nausea, dizziness and fatigue complaints. 

PMID- 25610104
TI  - Left atrial myxoma and concomitant atherosclerotic coronary artery disease.
AB  - Here we describe the case of a 71-year-old female patient who was admitted to our
      department with acute coronary syndrome. Trans-thoracic echocardiography
      evaluation to assess left ventricular functions incidentally detected a left
      atrial mass attached to the inter-atrial septum together with a left ventricular
      segmental wall motion abnormality due to acute anterior myocardial infarction.
      Coronary angiography revealed diffuse coronary artery disease. Because early
      surgery was not advised due to the high mortality risk, successful coronary
      angioplasty and stenting was performed in this emergecy situation. It may be
      informative to study the images from the echocardiography prior to angiography in
      this study as well as to determine the anticipated signs that may affect the
      treatment options for similar patients. 

PMID- 25610105
TI  - Primary hemangiopericytoma of the parietal bone: a case report.
AB  - Hemangiopericytomas are rare hypervascular tumors arising from Zimmerman's
      pericytes. They usually occur in the soft tissue, and intraosseous lesions are
      very rare. Surgical excision is the first choice for treatment. Many studies show
      that patients should be monitored for some time following treatment because of a
      high rate of recurrence and metastasis after radical resection. This report
      introduces a 56-year-old patient with a hemangiopericytoma in his parietal bone.
      KEYWORDS: Parietal bone, Hemangiopericytoma.

PMID- 25610106
TI  - Cysto-biliary rupture in hepatic hydatid disease: magnetic resonance
      cholangiopancreatography and endoscopic retrograde cholangiopancreatography
      findings.

PMID- 25610107
TI  - A new method for hepatic resection and hemostasis: absorbable plaque and suture.
AB  - OBJECTIVE: Blunt and penetrating hepatic injuries are conditions that are
      frequently encountered in emergency surgeries, and they involve high mortality
      morbidity. In the handling of such injuries, methods ranging from the application
      of simple cauterization and suturing for hemostasis to hepatic lobectomies, which
      might involve the removal of the greater part of the organ, have been defined.
      Due to the organ's fragility and susceptibility to bleeding, elective hepatic
      resections necessitate both surgical experience and technological equipment.
      Therefore, the demand still exists for an affordable and easy-to-use-method that
      could be applied by all centers. MATERIALS AND METHODS: To meet this demand, we
      have developed a method of hemorrhage control via sutures supported by absorbable
      plaques that provide effective compression and prevent the suture from cutting
      the tissue during the application of the sutures in the treatment of such fragile
      organs as the liver. In our method, we have achieved hemostasis by bilaterally
      compressing the tissue through strong ties after placing, on the part of the
      tissue on which the sutures are applied, absorbable and flexible plaques that
      prevent the suture from cutting the tissue during the application of a
      polyglactin suture to the solid organ. To prevent dislocation of the plaques, we
      have fastened the sutures by reeving them through the holes made in the plaques.
      RESULTS: We have demonstrated the success and the practicality of our method by
      applying it on four pigs; we experimentally inflicted hepatic injuries on two
      pigs, and we performed resection on the other two pigs. The hepatic hemorrhages
      we developed in both of the animals were successfully restrained by the use of
      our method. On the other hand, two resections were performed on the right and
      left lobes of the other two animals. There were no hemorrhages during the
      surgery, and the procedure took 45 minutes in total. No postoperative
      complications occurred. While the liver function test values were high on the
      seventh day, due to the operation, they were observed to be normal on the
      thirtieth day. After the laparotomies, performed six months later, we observed
      that the plaques as well as the sutures were absorbed and that the injured
      tissues were completely healed. Additionally, it was observed during the
      pathological examination that the tissues beneath the area of application were
      healed through fibrosis and that the liver had no other pathologies. CONCLUSIONS:
      In conclusion, we believe that the method can be safely used in hepatic
      resections or traumatic hemorrhages in the proper locations.

PMID- 25610108
TI  - Simultaneous bilateral spontaneous pneumothorax: a rare emergency clinical
      condition.
AB  - OBJECTIVE: Spontaneous pneumothorax is a disease that may cause serious
      respiratory distress and can be a life-threatening condition. A total of 1.3% of
      all spontaneous pneumothorax cases are simultaneous bilateral spontaneous
      pneumothorax (SBSP). In this study, because of its rarity, we discuss SBSP cases
      in light of previously reported cases. MATERIALS AND METHODS: Between January
      2004 and December 2009, SBSP was detected in five patients. RESULTS: All patients
      were male, and the mean patient age was 18.6 (between 16 and 22 years of age).
      All patients had various degrees of dyspnea and chest pain. All diagnoses were
      established by chest X-rays. Two patients (40%) had primary spontaneous
      pneumothorax (PSP), and three (60%) had secondary spontaneous pneumothorax (SSP)
      (two patients had silicosis, and one had Staphylococcus aureus pneumonia).
      Previously, bilateral tube thoracostomies were performed on all patients. One PSP
      patient had a left apical pleurectomy with axillary thoracotomy; the other had a
      right apical pleurectomy. Tetracycline pleurodesis was performed on one of the
      silicosis patients. No additional surgical procedure or pleurodesis was performed
      on the other silicosis patient or on the pneumonia patient. No recurrence of
      pneumothorax was observed in any patient. CONCLUSIONS: SBSP could be a life
      threatening condition; therefore, urgent diagnosis and appropriate treatment of
      this condition can save patients' lives.

PMID- 25610109
TI  - Distribution of HLA Tissue Groups in Patients with Gastric Cancer.
AB  - OBJECTIVE: Gastric cancer is an important disease that is seen all over the world
      and that threats public health. At the same time, gastric cancer is a
      heterogeneous disorder with multifactorial etiologies. Recent studies have shown
      a significant association between HLA antigens and gastric adenocarcinoma. The
      aim of the present study was to determine the distribution of HLA class I (HLA-A,
      B and C) and class II (HLA-DR, DQ and DP) antigens in Turkish patients with
      gastric adenocarcinoma. MATERIALS AND METHODS: HLA alleles or HLA haplotypes
      associated with gastric cancer were established in the Turkish population using
      PSR-SSP analysis in 71 unrelated patients with gastric cancer and in 82 unrelated
      healthy controls. The statistical significance of differences in allele
      frequencies between patients and controls was measured by the Chi-square test
      with Yates's correction. RESULTS: The study revealed that the HLA-Cw5 antigen is
      more prevalent in patients with gastric cancer (p=0.042) and that the HLA-DRB1*15
      antigen is more prevelent in the control group (p=0.021). CONCLUSION: It is
      probable that HLA-Cw5 is a risk factor for gastric cancer whereas HLA-DRB1*15
      plays a protective role for this disease. The results show that different loci on
      HLA may control resistance to or tendency for any disease in different societies;
      each society should determine its own tissue group.

PMID- 25610110
TI  - The use of multi detector computed tomography in assessing the retroaortic left
      renal vein and accompanying vessel anomalies.
AB  - OBJECTIVE: Because renal venous variations possess potential hazards during
      abdominal aortic surgery or laparoscopic donor nephrectomy, the detailed
      preoperative evaluation of the renal vessels with angiography should be performed
      to avoid vascular injuries. We present multidetector row computed tomography
      (MDCT) findings of the retroaortic left renal vein (RLRV) with other vascular
      variations. MATERIALS AND METHODS: Twenty-two patients with RLRV were evaluated
      with MDCT using multiplanar images, MIP images, and 3D volume rendering. RESULTS:
      The RLRVs with accessory renal vessels and other variant veins draining into the
      left renal vein were effectively evaluated in all patients. CONCLUSIONS: MDCT
      angiography is an effective technique for evaluating abdominal vessels, and it
      presents adequate images of renal vessels and vascular variations, which pose
      importance before abdominal surgery.

PMID- 25610111
TI  - Usefulness of serum pepsinogen levels as a screening test for atrophic gastritis
      and gastric cancer.
AB  - OBJECTIVE: The purpose of our study was to research the applicability of
      measuring serum pepsinogen I (PG I) and PG I/pepsinogen II (PG II) ratios as
      screening tests for atrophic gastritis, which is the most important
      predisposition for stomach cancer. MATERIALS AND METHODS: We measured serum
      pepsinogen levels in non-specific gastritis, atrophic gastritis and gastric
      cancer using a radioimmunoassay method. We included in this study 30 healthy
      control, 30 nonspecific gastritis, 30 atrophic gastritis and 50 gastric cancer
      cases. RESULTS: The serum PG I level was statistically higher in the control
      group and in the patient group with chronic nonspecific gastritis compared to the
      patient groups with chronic atrophic gastritis and stomach cancer (p<0.05). The
      best cutoff values for diagnosing stomach cancer using serum PG I and PG I / PG
      II ratios were found to be <25 ng/ml for PG I and <3.0 for PG I / PG II. The same
      cut-off values were also most effective for the patients with atrophic gastritis.
      CONCLUSIONS: Serum pepsinogen screening was shown to be a practical predictor of
      stomach cancer and atrophic gastritis, the most important predisposing lesion for
      stomach cancer. Although the diagnosis of stomach cancers localized in the
      pylorus and cardia via this method is difficult, we believe that the detection of
      early-stage cancers that develop following chronic atrophic gastritis in
      particular will be possible, and therefore the morbidity and mortality of stomach
      cancer will be decreased.

PMID- 25610112
TI  - The frequency of familial mediterranean Fever related amyloidosis in renal
      waiting list for transplantation.
AB  - OBJECTIVE: Our goal is to investigate the distribution of MEFV mutations in
      patients with renal amyloidosis who are in renal transplant waiting list which is
      prepared for transplantation. MATERIALS AND METHODS: FMF was diagnosed in 25 of
      the 297 patients between the years 2004 and 2008, who were involved in the study
      (15 male, 10 female; age 34+/-7.8). 5 out of 25 patients were transplanted,
      remaining were waiting for Tx. Biopsy results were amyloidosis and taken from
      renal (n:16), rectal (n:8) and duodenal (1).All of them were carrier of mutations
      in both pyrin alleles.The primer cause of chronic renal failure in our group was
      secondary AA amyloidosis. DNA was isolated from 25 whole blood samples. The
      NanoChip Molecular Biology Workstation (Nanogen) uses electronic microarrays for
      mutation detection. Exon 2,3,5 and 10 of pyrin gene genotypes were identified in
      the NanoChip. RESULTS: Genetic analysis of the patients demonstrated that each
      subject carries either homozygote or compound heterozygote mutations of the gene.
      The most common mutations were M694V, V726A, E148Q and M680I. CONCLUSIONS: The
      clinic manifestation and complain of our patients were febrile and painful
      attacks such as in the abdomen, chest and joints due to inflammation of the
      peritoneum, pleura and synovial membrane. The major problem in FMF is the
      occurrence of amyloidosis that primarily affects the kidneys causing proteinuria
      and renal failure. Dialysis and renal transplantation can be treatment, but it is
      important to diagnose FMF at earliest stages. The percentage of FMF patients in
      our waiting list was 8.4%. Moreover, in our region FMF incidence is highly
      frequent, so FMF should be chased by genetically so as to prevent chronic renal
      failure due to amyloidosis.

PMID- 25610113
TI  - Silicosis due to Denim Sandblasting in Young People: MDCT Findings.
AB  - OBJECTIVE: Occupational lung disease due to silica dust is one of the most common
      work-related injuries. In denim sandblasting, workers are exposed to silica that
      may cause immediate mortality, especially in young people. The aim of this study
      was to assess the multidetector computed tomography (MDCT) findings of silicosis
      in denim sandblasters and to better define the role of MDCT in the early
      detection of silicosis. MATERIALS AND METHODS: The study included 12 consecutive
      male patients who were admitted to a pulmonary outpatient clinic between April
      2009 and December 2009. All patients had been working as sandblasters for at
      least one year. All patients underwent chest CT examinations for suspected
      silicosis. Two radiologists independently assessed the images for the presence
      and distribution of airspace consolidation, ground-glass opacity, nodules,
      interlobular septal thickening, parenchymal bands, fibrosis, masses, traction
      bronchiectasis, honeycombing, lobular low-attenuation areas, emphysema, pleural
      effusion or thickening, and mediastinal or hilar adenopathy. RESULTS: MDCT
      detected parenchymal abnormalities in the lungs in eight (67%) of the twelve
      patients. The most common MDCT finding was ground glass opacity (58%). Other
      common findings were parencyhmal nodules and interlobular septal thickening,
      predominantly in the upper zones. Nodules were detected in six (50%) of the
      twelve patients. In four cases (67%), the nodules were numerous (>10), were
      predominantly smaller than 10 mm, and were centrilobular in distribution. In five
      (42%) of the 12 patients, interlobular septal thickening was detected. Only one
      (8%) patient presented with airspace consolidation; this was bilateral in the
      upper zones and associated with air bronchograms. In one (8%) patient there were
      several traction bronchiectases in the upper zones. None of the patients
      presented with pleural effusion, thickening, or honeycombing. Enlarged
      mediastinal nodes were identified in half of the patients, predominantly in the
      precarinal, paratracheal, and prevascular regions. No egg-shell calcification was
      detected. One (8%) patient presented with punctate calcification in the hilar
      region. CONCLUSIONS: Early detection of silicosis is important because it may
      cause immediate mortality, especially in young people. Enlarged mediastinal lymph
      nodes, centrilobular nodules, interlobular septal thickening, and patchy ground
      glass opacity may be early MDCT findings of silicosis. Thus, MDCT plays an
      important role in the early detection of silicosis in denim sandblasters.

PMID- 25610114
TI  - Does the visceral fat tissue show better correlation with the fatty replacement
      of the pancreas than with BMI?
AB  - OBJECTIVE: Obesity is a risk factor of fatty replacement of the pancreas. We
      aimed to investigate whether there is a better correlation between the visceral
      fat tissue and the fatty infiltration of the pancreas than with the BMI.
      MATERIALS AND METHODS: One hundred-eighteen patients were visually divided into
      three groups according to the pattern of the fatty infiltration of the pancreas.
      Group 0 (n=70) has no fatty infiltration, Group 1 (n=23) has fatty infiltration
      on the head only, and Group 2 (n=25) has fatty infiltration on the entire
      pancreas. Additionally, the attenuation numbers (HU) were measured separately at
      the head, body and tail of the pancreas on contrast-enhanced Computed Tomography
      CT. The sum of the attenuation number of each part of the pancreas was calculated
      as the attenuation number of the pancreas. A CT-scan was used to calculate the
      visceral fat area (cm(2)). Correlation coefficients were determined between the
      visceral fat area and fatty infiltration of the pancreas and the BMI. RESULTS:
      The visceral fat area showed a stronger correlation with the attenuation number
      of the pancreas than the BMI (r=-0.552, r=-0.345 and p=0.0001, p=0.0001,
      respectively). The difference existed between the Groups 0 and 1 (p=0.0001) or
      Groups 0 and 2 (p=0.0001) in terms of visceral fat area. The difference existed
      only between Group 0 and Group 2 in terms of BMI (p=0.006). CONCLUSIONS: The
      visceral fat tissue area has a stronger correlation than the BMI in the fatty
      infiltration of the pancreas.

PMID- 25610116
TI  - Atypical Colony Morphology of Staphylococcus lugdunensis Isolated from a Wound
      Specimen.
AB  - The incidence of infections due to coagulase-negative staphylococci (CoNS) has
      been steadily increasing in recent years. In this report, we describe an isolate
      of the CoNS Staphylococcus lugdunensis from a wound specimen with a colony
      morphology distinct from that of a classical S. lugdunensis colony. Specifically,
      wrinkled, medium-sized, beta hemolytic, opaque, rough white colonies were
      detected on blood agar. Catalase-positive, coagulase-negative, gram-positive
      cocci-yielding such colonies should be suspected of being S. lugdunensis. 

PMID- 25610115
TI  - Acute inhalation injury.
AB  - Inhaled substances may cause injury in pulmonary epithelium at various levels of
      respiratory tract, leading from simple symptoms to severe disease. Acute
      inhalation injury (AII) is not uncommon condition. There are certain high risk
      groups but AII may occur at various places including home or workplace.
      Environmental exposure is also possible. In addition to individual
      susceptibility, the characteristics of inhaled substances such as water
      solubility, size of substances and chemical properties may affect disease
      severity as well as its location. Although AII cases may recover in a few days
      but AII may cause long-term complications, even death. We aimed to discuss the
      effects of short-term exposures (minutes to hours) to toxic substances on the
      lungs. 

PMID- 25610117
TI  - Cerebral Venous Thrombosis and Pulmonary Embolism with Prothrombin G20210A Gene
      Mutation.
AB  - A 25-year-old man presented with symptoms of syncope, cough, headache and
      hemoptysis. Cranial MR and venography showed thrombus formation in the right
      transverse sinus and superior sagittal sinus. Computed tomographic pulmonary
      angiography (CTPA) showed an embolic thrombus in the right pulmonary truncus and
      lung abscess. The patient was young, and there were no signs of lower extremity
      deep venous thrombosis or other major risk factors for pulmonary embolism (PE)
      including cardiac anomaly. The only risk factor we were able to identify was the
      presence of the prothrombin G20210A gene mutation. Anticoagulant treatment with
      oral warfarin (10 mg daily) and imipenem (4X500 mg) was started. The patient was
      hospitalized for antibiotic and anticoagulation therapies for three weeks and was
      discharged on lifelong treatment with warfarin (5 mg daily). 

PMID- 25610118
TI  - A case report of cutaneous larva migrans.
AB  - Cutaneous larva migrans (CLM) is a helminthic infection most commonly found in
      tropical and subtropical geographic areas. However, with the ease and increase of
      foreign travel by many around the world, CLM is no longer confined to these
      areas. CLM is an erythematous, serpiginous, cutaneous eruption caused by
      accidental percutaneous penetration and subsequent migration of larvae. Here, we
      present a case diagnosed as CLM and treated with Albendazole. 

PMID- 25610119
TI  - The Successful Use of Enoxaparin in the Lack of Bivalirudin in a Patient with
      Chronic Lymphocytic Leukemia and Thrombocytopenia who Underwent Percutaneous
      Coronary Revascularization.
AB  - We present a patient with chronic lymphocytic leukemia and thrombocytopenia who
      underwent a percutaneous coronary intervention. Such patients are at increased
      risk for ischemic and hemorrhagic complications and the choice of anticoagulant
      therapy should be made very carefully. Unfractionated heparin or glycoprotein
      IIb/IIIa inhibitors may cause thrombocytopenia and increased bleeding.
      Bivalirudin therapy is safer in such patients. However, bivalirudin is not always
      available. We used enoxaparin, a low-molecular-weight heparin, as an
      anticoagulant in a case in which bivalirudin was not available. No ischemic or
      hemorrhagic complications were seen in the follow-up period. We suggest that low
      molecular-weight heparin may be effective and safe as an alternative to
      bivalirudin in patients with chronic lymphocytic leukemia and thrombocytopenia
      when bivalirudin is unavailable. 

PMID- 25610120
TI  - Pulsed radiofrequency application in the entrapment neuropathy of a sural nerve.
AB  - Compressive and entrapment neuropathy of the peroneal nerve is the most common
      entrapment syndrome in the lower limbs, often caused by mechanical or dynamic
      compression of a segment of nerve at the level of the fibula head. Because of its
      special anatomic situation, external compression while under trauma or traction
      is quite easy. A case of entrapment neuropathy syndrome in a 33-year-old man
      treated by pulse radiofrequency to the lateral cutaneous branch of the common
      peroneal nerve is presented. 

PMID- 25610121
TI  - Arterial Compression in a Young Adult due to the Presence of a Cervical Rib: CT
      and CT Angiographic Findings.

PMID- 25610122
TI  - The contribution of chemoreceptor-network injury to the development of
      respiratory arrest following subarachnoid hemorrhage.
AB  - OBJECTIVE: Respiratory arrest following brainstem herniation has been attributed
      to injuries resulting from compression of the respiratory centers. While it is
      widely perceived that the chemoreceptor network, consisting of the
      glossopharyngeal nerve and carotid body (GPN-CB), is essential for the modulation
      of respiration, its contribution to the development of respiratory arrest has not
      been investigated. Therefore, the aim of this study was to investigate whether
      injury to the GPN-CB occurs in animals with respiratory arrest caused by
      experimentally-induced subarachnoid hemorrhage. MATERIALS AND METHODS: Eighteen
      hybrid rabbits were used in this study. Four rabbits (n=4) were used to determine
      the normal structure of the GPN-CB. The remaining rabbits (n=14) received an
      autologous blood injection into the cisterna magna to produce a subarachnoid
      hemorrhage, after which they were observed for 20 days. The number of axons and
      the neuron density in the glossopharyngeal nerve and carotid body, respectively,
      were counted by stereological methods. The Mann-Whitney U test was used to
      analyze the results. RESULTS: Six of 14 rabbits died within the first week,
      likely due to brain swelling and crushing injuries that were observed in the
      brain stem and related structures. In control rabbits, the average neuronal
      density of the carotid body was 4250 +/-1250/mm(3), while the axonal density in
      the glossopharyngeal nerve was 18000+/-5100 mm(2). Conversely, in the dead
      rabbits, the degenerated neuron density of the carotid body was 2100+/-500/mm(3),
      while the degenerated axon density in the glossopharyngeal nerve was 8500+/-2550
      mm(2). In addition, histopathological lesions were more severe in the dead
      rabbits in terms of their glossopharyngeal nerve and carotid body. CONCLUSION:
      There is an important relationship between neurodegeneration in the GPN-CB and
      mortality rates following experimentally-induced hemorrhage. This relationship
      suggests that injury to the GPN-CB network disrupts the breathing reflex and
      results in respiratory arrest following a subarachnoid hemorrhage (SAH).

PMID- 25610123
TI  - Determination of linear x-ray attenuation coefficients of pathological brain
      tissues and use of filters in tissue contrast enhancement in computed tomography.
AB  - OBJECTIVE: X-ray attenuation coefficients are used in common radiological,
      pathological and spectroscopic examinations and in the determination of the
      radiation dose distribution in biological tissues. In radiology, these
      coefficients enable diagnosis by differentiating the abnormal tissues from the
      normal ones using their morphological structure and contrast differences. In this
      study, our aim is to precisely determine the linear x-ray attenuation
      coefficients of pathological brain tissues and to use x-ray beam filters to
      enhance the tissue contrast in computed tomography. MATERIALS AND METHODS: To
      directly measure the relative linear attenuation coefficients, an energy
      dispersive x-ray spectroscopy system (EDXRS-Canberra, Si(Li) with DSA-1000
      spectrum analyzer 1998; CT, USA) was used with collimators and a medical-purpose
      x-ray tube (Siemens, Siremobil, 1985; Erlangen, Germany) in a linear geometry.
      RESULTS: Using a Mo filter with Computed Tomography CT and photon energies from
      15 to 25 keV, EDXRS acquisitions were found to significantly distinguish grades
      of brain tumors (p<0.05). For the data acquired from CT systems with the
      decreasing filtered photon mean energy, the x-ray attenuation coefficients (i.e.,
      the Hounsfield units) show that the ratio of EDXRS to CT for water's attenuation
      coefficient are increased. With our suggested x-ray filters, the tissue contrast
      has been found to be increased in ex vivo brain tumor slices compared with slices
      scanned in conventional CT scanners. CONCLUSION: X-ray attenuations measured with
      the EDXRS are found to be statistically more reliable because of the length of
      acquisition times in this study.

PMID- 25610124
TI  - Diffusion-weighted magnetic resonance imaging in evaluation of gastric cancer.
AB  - OBJECTIVE: To investigate the role of diffusion-weighted magnetic resonance
      imaging (DW-MRI) in the diagnosis of gastric tumors and discuss the diagnostic
      importance and potential use of apparent diffusion coefficient (ADC)
      measurements. MATERIALS AND METHODS: Beginning in March 2009, DW-MRI was added to
      the routine abdominal and pelvic MR examination for all patients imaged at our
      institution. A total of 21 patients (12 men and 9 women; mean age 55+/-6.3SD,
      range: 39-74 years) with known gastric malignancy were referred to our MR unit.
      All MRI examinations were performed using a 1.5-T MRI scanner (Magnetom Avanto,
      Siemens Healthcare). The evaluation of the DW-MRI examinations was made by
      radiologists' consensus. Changes in the signal intensity of the lesions were
      determined by their appearance in images at b=50, 400, and 800 s/mm(2) and in ADC
      maps. Results were compared with histopathological findings. RESULTS: All of the
      gastric tumors in this study showed high signal intensity in DW-MRI and low
      signal intensity in ADC maps. Mean ADC values for gastric tumor and normal
      gastric wall were 0.892+/-0.23 SD mm(2)/s and 1.453+/-0.35 SD mm(2)/s
      respectively. The mean ADC values of gastric tumors were significantly lower than
      that of the normal gastric wall. CONCLUSION: DW-MRI and ADC values together can
      successfully differentiate gastric tumors from normal gastric wall.

PMID- 25610125
TI  - Dexmedetomidine in the supratentorial craniotomy.
AB  - OBJECTIVE: In this double-blind prospective clinical study, we investigated the
      effects of fentanyl and dexmedetomidine as adjuvant agents in supratentorial
      craniotomies on the following: hemodynamic changes during perioperative and
      recovery periods, brain edema perioperatively, recovery times and side effects,
      such as hypertension, shivering, nausea and vomiting. MATERIALS AND METHODS:
      Thirty consenting ASA physical status I-II patients undergoing intracranial tumor
      surgery were randomly divided in two groups. In group D (n=15), dexmedetomidine
      was infused as a 1 MUg/kg bolus dose 10 minutes before induction of anesthesia
      and maintained with 0.4-0.5 MUg/kg/min during the operation. In group F (n=15),
      animals were given fentanyl 0.02 MUg/kg/min as an infusion for anesthesia
      maintenance. At induction, fentanyl was given as a 2 MUg/kg dose in group D and
      as a 4 MUg/kg dose in group F. Hemodynamic changes, recovery times and
      postoperative side effects were recorded before induction, during the
      perioperative period and 24 hours postoperatively. RESULTS: In group D; MAP and
      HR values after intubation, after skull clamp insertion and after extubation were
      lower than in group F (p<0.05). In group D, cerebral relaxation scores were also
      significantly lower. Recovery times were found to be shorter in group D as
      compared to group F; the same trend was observed for the supplemental opioid
      requirement. During the postoperative period, there was no shivering, nausea or
      vomiting in group D, but in group F, 3 patients complained of shivering, and 2
      patients experienced nausea and vomiting. CONCLUSION: In our study, we found that
      dexmedetomidine controlled the hemodynamic changes better than fentanyl
      perioperatively, after extubation and during the early postoperative period. Our
      results suggest that that dexmedetomidine is safer and more effective in
      controlling hemodynamic changes during surgical stimulation than the standard
      agents used in neuroanesthesia.

PMID- 25610126
TI  - A stereological assessment method for estimating the surface area of cycloids.
AB  - OBJECTIVE: In this study, we sought to determine differences in estimations of
      surface area made by classical vertical uniform random (VUR) section series and
      vertical section series obtained perpendicular to a fixed horizontal plane.
      MATERIALS AND METHODS: One volunteer subject (male, 25 years of age) with no
      neurological deficit was chosen at random from a bank of controls in the magnetic
      resonance (MR) image data library of the Department of Radiology. First, a soccer
      ball with known geometrical features (radius: 9.75 cm) was imaged using a T1
      weighted MR scanner at 5-mm thickness (total 40 sections) to test the validity
      and reliability of surface area and volume measurements obtained via
      stereological methods. Second, T1-weighted MR section profiles were obtained from
      a volunteer individual. Surface area and volume estimation procedures were
      carried out using the Stereo Investigator 6, MicroBright-Field, Inc., USA.
      CONCLUSIONS: We determined that there are no differences in either surface area
      or volume estimations made using VUR sections and direct vertical sections. We
      have performed an exhaustive series analysis with a variety of objects.

PMID- 25610127
TI  - Smoking prevalance and the degree of nicotine dependence among healthcare workers
      at the ataturk university medical facility.
AB  - OBJECTIVE: In this study, we aimed to investigate smoking prevalence and the
      degree of nicotine dependence in our hospital healthcare workers. MATERIALS AND
      METHODS: This study was conducted between January 2008 and June 2008 in our
      hospital (Medical Facility of Ataturk University). A total of 691 (370 females,
      321 males) subjects were included in this study. A questionnaire, including
      demographic findings, tobacco consumption information and the Fagerstrom nicotine
      dependence test, was distributed to healthcare workers and collected. RESULTS:
      The questionnaire was answered by 691 health workers, 46.5% of whom were male,
      and 53.5% of whom were female. Overall, the rate of smoking was 36.9%; 48% of
      males and 27.6% of females were current smokers. When classified according to
      clinic, the greatest rate of smoking was in the psychiatry clinic (60.0%), and
      the lowest rate of smoking was in the ear, nose and throat (ENT) Clinic (0.0%).
      Thirty-four percent of nurses, 18.7% of doctors, 45.5% of officers, and 50.4% of
      ancillary staff were smokers. According to education level, 50% of the cases
      (smokers) graduated from primary school, 45% of the cases graduated from high
      school and 26.9% of the cases graduated from university. The major reason for the
      initiation of smoking was attention-seeking behavior. The age at smoking
      initiation was 7 to 20 years in 83.9% of cases and 21 to 35 years in the
      remaining 16.1%. Thirty-five percent of smokers had very low levels of
      dependence, while 11.9% had very high levels dependence. Ninety-two percent of
      cases indicated they would prefer to work at a smoke-free hospital. Ninety-five
      percent of cases would support making this facility a smoke-free hospital.
      CONCLUSION: The smoking rate was 36.9% amongst our hospital health workers.
      Smoking prevalence was higher in males (48%) than females (27.6%). The greatest
      smoking rate was amongst ancillary staff. Ninety-five percent of healthcare
      workers were supportive of a law requiring hospitals to be smoke-free.

PMID- 25610128
TI  - Subcutaneous infusion ports via the internal jugular vein: single center
      experience.
AB  - OBJECTIVE: Our purpose is to report and review the results and early
      complications of subcutaneous infusion port placement by our interventional
      radiology department. MATERIALS AND METHODS: Three-hundred twenty-five
      subcutaneous infusion ports were placed in 320 patients between January 2005 and
      May 2010. Ports were placed under both general and local anesthesia. Five
      patients were catheterized twice. The internal jugular veins were used for
      access. Both ultrasono-graphic and fluoroscopic guidance were used in our
      interventions. Retrospectively, we evaluated the ports' duration time. RESULTS:
      Our technical success rate was 100% and only five complications occurred during
      port placement. The common carotid arteries were punctured in three patients but
      bleeding stopped ten minutes following withdrawal of the needle and artery
      compression. An air embolism occurred in two patients and both were successfully
      treated with good positioning and suctioning. Early catheter removal was required
      in five patients. One patient had a right internal jugular vein thrombosis, three
      patients had catheter occlusions and two patients had catheter fractures. The
      mean duration of catheter usage was 354 days (range: 2 to 1,478 days).
      CONCLUSION: Image guided placement of infusion ports has a greater success rate
      and lower early complication rate when compared with the unguided series. The
      right internal jugular vein is the first choice for infusion port access.

PMID- 25610129
TI  - Comparison of power Doppler ultrasound with gray scale transrectal ultrasound in
      predicting cancer positive prostate biopsy cores.
AB  - OBJECTIVE: The aim of this study is to compare the effect of transrectal power
      Doppler ultrasound (PDUS) and gray scale transrectal ultrasound (TRUS) for the
      diagnosis of prostate cancer. MATERIALS AND METHODS: Seventy-six patients
      evaluated with transrectal PDUS and TRUS underwent eight systematic TRUS guided
      core-needle biopsies, with additional cores from abnormal areas. Histologic
      diagnoses were classified as benign prostatic hyperplasia, chronic prostatitis,
      intraepithelial neoplasia and adenocarcinoma. TRUS and PDUS findings of the cases
      were recorded. RESULTS: PDUS sensitivity, specificity, positive predictive value
      (PPV) and negative predictive values were 81%, 81%, 54% and 94%, respectively.
      PDUS had a greater sensitivity and specificity than TRUS (43% and 60%,
      respectively) and identified cancer cases more accurately (Table 2). CONCLUSION:
      Hypervascular foci in PDUS signify suitable zones for biopsy. When combined with
      systematic TRUS guided biopsy, PDUS increases the cancer detection rate with
      additional biopsies from suspicious hypervascular foci. Transrectal PDUS guided
      biopsy should be combined with gray scale TRUS guided biopsy to increase accuracy
      in the diagnosis of prostate cancer.

PMID- 25610130
TI  - Nutritional rickets in Turkey.
AB  - Nutritional rickets (NR) remains the most common form of developmental bone
      disease, in spite of the efforts of clinicians and health care providers to
      reduce the incidence of the disease in Turkey. Today, it is well known that the
      etiology of NR exists along a spectrum ranging from isolated vitamin D deficiency
      to isolated calcium deficiency. In Turkey, almost all NR results from vita-min D
      deficiency that may have temporary but profound effects on short- and long-term
      skeletal development. Recent evidence suggests that vitamin D deficiency during
      infancy may predispose a patient to diseases such as diabetes mellitus, cancer,
      multiple sclerosis, etc. The factors responsible for the high prevalence of
      vitamin D deficiency in developing countries and its resurgence in developed
      countries include the following: limited sunshine exposure as individuals spend
      more time indoors watching television and working on computers or intentional
      sunshine avoidance for skin cancer prevention. Traditional clothing (covered
      dress) further limits the exposure to sunshine and thus decreases the endogenous
      synthesis of vitamin D. In Turkey, maternal vitamin D deficiency and breast
      feeding without supplementation are the most prominent reasons. The diagnosis of
      NR is established with a thorough history and physical examination and confirmed
      by laboratory evaluation. In conclusion, recent literature has drawn attention to
      the supplemental doses of vitamin D required to achieve a serum 25-hydroxyvitamin
      D level of at least 20 ng/ml (50 nmol/l), the serum concentration that is needed
      to optimize absorption of dietary calcium, suppress excess secretion of
      parathyroid hormone, and reduce fracture risk as well as prevent long-term
      negative effects. 

PMID- 25610131
TI  - Infant botulism.
AB  - Infant botulism is a rare condition caused by intestinal colonization with
      Clostridium botulinum. The enteric toxin causes intestinal immobility and
      progressive descending paralysis due to the effect on acetylcholine release at
      the neuromuscular junction and other cholinergic nerve terminals, particularly in
      the gut. Herein, we report an infant with infantile botulism because of rare
      clinically entity, with early diagnosis and appropriate treatment recover no
      squeal. 

PMID- 25610132
TI  - A Rare Presentation of an Entrapment in a Liver Transplant Candidate Depicted by
      MDCT Angiography.
AB  - Hypertrophic caudate lobe veins can mimic a normal venous configuration. In cases
      of multiple vascular collaterals, Doppler evaluations must be conducted, and the
      flow direction of these veins as well as the IVC should be evaluated. If the flow
      in the IVC is reversed, Budd-Chiari syndrome should be suspected; moreover, at
      the supra diaphragmatic level, which may be considered a blind spot, particularly
      for radiologists, a web should be searched for in the area where the IVC opens
      into the right atrium. In this study, we present the unique findings of
      multidetector computed tomography (MDCT) angiography for a liver transplant
      candidate with Budd-Chiari syndrome caused by a web in the proximal IVC. 

PMID- 25610133
TI  - Self-bloodletting: an unusual form of self-mutilation in adolescence.
AB  - In this paper, we introduce an adolescent suffering from a rare form of self
      mutilation, "self-bloodletting", and discuss dynamics of this maladaptive
      behavior. Deliberate bloodletting is a rare, but not unheard of, form of self
      mutilation associated with eating and personality disorders. Although there are
      already several case reports in the adult psychiatry literature regarding the
      clinical features of Lasthenie de Ferjol Syndrome or factitious anemia, this is
      the first reported adolescent case of self-bloodletting. 

PMID- 25610134
TI  - A case of anomalous left coronary artery arising from the pulmonary artery in
      adulthood: multidetector computed tomography coronary angiography findings.
AB  - Anomalous left coronary artery arising from the pulmonary artery (ALCAPA) is a
      rare but very serious congenital coronary artery anomaly. Multidetector computed
      tomography (MDCT) coronary angiography has recently become the gold standard for
      depicting anatomical variations and anomalies of the coronary arteries because
      the origin and course of anomalous arteries can be demonstrated very accurately
      by this technique. In this report, we present a case of 22-year-old female who
      was admitted to our emergency department with cardiac arrest. In the course of
      diagnosis, MDCT coronary angiography revealed a left coronary artery arising from
      the pulmonary artery as well as marked dilatation of the coronary arteries. 

PMID- 25610135
TI  - Krukenberg Tumor: CT and PET-CT Findings.

PMID- 25610136
TI  - Scheuermann's Disease of the Thoracolumbar Spine in a Boy.

PMID- 25610137
TI  - The relationships of serum prealbumin levels with parameters that indicate
      severity of disease and emphysema pattern in patients with stable chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: Malnutrition, which is a complication frequently observed in chronic
      obstructive pulmonary disease (COPD) and negatively affects prognosis, has become
      a parameter that must be monitored. Even though various methods are applied to
      assess malnutrition, biochemical parameters, especially serum prealbumin levels,
      are useful. MATERIALS AND METHODS: The relationships between serum prealbumin
      levels, which we used as an indicator of malnutrition, with the severity of
      disease and the parameters predicting emphysema in stable COPD patients with no
      additional health problems were determined in this prospective study. RESULTS:
      One hundred stable COPD patients were evaluated prospectively. Serum prealbumin
      levels had a negative correlation with the total number of hospitalizations due
      to acute exacerbation, total hospitalization time, and average number of annual
      hospitalizations, whereas it showed a positive correlation with FEV1 and
      FEV1/FVC% values. Serum prealbumin levels were positively correlated with the
      length of the line connecting the costophrenic sinus to the dome of the
      diaphragm, which is used to assess the presence of emphysema and was negatively
      correlated with retrosternal distance. Also, in COPD patients with low prealbumin
      levels, while the FEV1 and FEV1/FVC% values and the length of the line connecting
      the costophrenic sinus to the diaphragm dome significantly decreased, the
      retrosternal distance dramatically increased compared to COPD patients with
      normal prealbumin levels. CONCLUSION: Serum prealbumin levels were convenient for
      monitoring malnutrition in COPD, were correlated with spirometric and anamnestic
      data indicating the severity of COPD, and were useful in distinguishing the
      subtype of COPD due to its decrease in the presence of emphysema.

PMID- 25610138
TI  - Lung cancer incidence in erzurum city.
AB  - OBJECTIVE: Known as an uncommon disease at the beginning of the 20(th) century,
      lung cancer has been the most frequent cause of cancer-related deaths in males
      since the 1950s and in females in the last two decades. The aim of this study was
      to determine the lung cancer incidence in Erzurum; its clinical properties,
      cancer subtypes, and application phases; the relationships of tumors with
      parameters of cigarette smoking and nutrition; radiological properties of the
      tumors; and the methods of diagnosis. MATERIALS AND METHODS: This study analyzed
      data from a prospective database. The study included the patients who applied in
      2005 to the Chest Disease, Chest Surgery, Medical Oncology or Radiation Oncology
      section of Research Hospital, Faculty of Medicine, Ataturk University; the
      Erzurum Nihat Kitapci Chest Diseases Hospital; or the Palandoken State Hospital
      and were diagnosed with lung cancer. A standard questionnaire was used to obtain
      information about the patients. The figures of the 2005 census issued by the
      State Institute of Statistics were used for incidence calculations. RESULTS:
      During the study period, 255 patients with a lung cancer diagnosis were accepted,
      220 of whom were male (86.3%) and 35 were female (13.7%). The mean age of the
      patients was 63+/-1 years. The lung cancer incidence in Erzurum according to the
      data given by the hospitals that can diagnose lung cancer was determined to be
      14.4/100.000. Lung cancer frequency increased with age, it was observed in males
      six times more frequently than females, and histopathologically non-small cell
      lung cancer and advanced phase lung cancer were more frequent. CONCLUSION: The
      lung cancer incidence for Erzurum was not different from that reported in other
      studies carried out both in the region and the whole country, and the lung cancer
      diagnosis was related to advanced age, male sexuality, active smoking and low
      socioeconomic state.

PMID- 25610139
TI  - Annular pancreas in children: a decade of experience.
AB  - OBJECTIVE: Annular pancreas is an uncommon cause of duodenal obstruction in
      children. In this study, the clinical, radiological, and prognostic findings
      related to this disorder over a 12-year review period were analyzed. MATERIALS
      AND METHODS: A retrospective review of 22 patients with annular pancreas who were
      treated with surgical repair between April 1998 and February 2010 was performed
      at two different pediatric surgical units. Presenting symptoms, associated
      anomalies, radiological findings, the type of surgery performed, postoperative
      outcomes, and complications were analyzed. RESULTS: Twenty-two patients were
      identified. Thirteen of the 22 patients (59.1%) were born prematurely, 11
      patients (50%) had low birth weight, 2 patients (9.1%) had very low birth weight
      and 1 patient (4.5%) had extremely low birth weight. The mean birth weight was
      2285.23+/-675.12 g. (970-3300). All patients presented with vomiting, which was
      bilious in nine (40.9%). Nine patients (40.9%) had chromosomal anomalies.
      Corrective surgery consisted of duodenoduodenostomy in 9 patients (40.9 %),
      duodenojejunostomy in 9 patients (40.9%), and gastrojejunostomy in 4 patients
      (18.1%). Fourteen of the 22 patients have survived (63.6%). The causes of death
      were combinations of sepsis, pneumonia, brain hemorrhage, and cardiac anomaly.
      CONCLUSION: Infants with annular pancreas associated with duodenal obstruction
      were often born prematurely and/or had low birth weights; many had cardiovascular
      anomalies. Annular pancreas associated with duodenal obstruction correlated
      strongly with the trisomy 21 karyotype among the chromosomal anomalies, as did
      duodenal atresia. The oral feeding tolerance time was nearly the same for all
      patients regardless of the surgical procedure used.

PMID- 25610140
TI  - Evaluation of 143 cases of immune thrombocytopenic purpura with regards to
      clinical course and response to treatment.
AB  - OBJECTIVE: Immune thrombocytopenic purpura (ITP) is also known as idiopathic
      thrombocytopenic purpura. Increased platelet destruction and insufficient
      platelet production are both responsible for its etiopathogenesis. ITP can be
      diagnosed after excluding other possible causes of thrombocytopenia. MATERIALS
      AND METHODS: One hundred forty-three cases of chronic ITP that were monitored in
      a hematology clinic were retrospectively evaluated. All cases received first line
      treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases
      and corticosteroid-dependent (CD) cases underwent splenectomies. RESULTS: The
      rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases
      (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse
      cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41,
      including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter
      pylori (Hp) eradication, immunosuppressive agents and danazol treatments were
      administered to patients (n=10, n=14 and n=4, respectively). Currently, 13
      patients are being monitored without treatment. Fifteen patients who were non
      responsive to Hp eradication treatment, immunosuppressive treatment or danazol
      treatment are still being monitored without any treatment. CONCLUSION: Optimal
      treatment is not available for splenectomy-resistant cases of ITP. The response
      rates for Hp eradication treatment, immunosuppressive treatments and anabolic
      agents are low. Therefore, larger studies with more patients are required using
      new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20
      monoclonal antibodies.

PMID- 25610141
TI  - The relationship between knee osteoarthritis and osteoporosis.
AB  - OBJECTIVE: The aim of this study was to investigate the association between knee
      osteoarthritis (OA) and bone mineral density (BMD) in the femur and lumbar
      vertebrae. MATERIALS AND METHODS: A total of 74 female patients (mean age 61.9 +/
      9.1 years, mean body mass index 27.09+/-4.24) diagnosed with knee OA were
      included in this study. To assess knee OA, bilateral weight-bearing antero
      posterior knee radiographs were taken and graded from 0 to 4 according to
      Kellgren-Lawrence criteria. The BMD of the subjects was measured using dual
      energy X-ray absorptiometry (DEXA). BMD measurements of those with OA were
      compared with those without OA. RESULTS: While there was no correlation between
      BMD and the grade of knee OA, a significant negative correlation was found
      between age and femur BMD. Body mass index was positively correlated with OA and
      negatively correlated with OP. CONCLUSION: Further investigations are needed to
      demonstrate the association between knee OA and BMD.

PMID- 25610142
TI  - Multi-detector row computed tomography findings of pelvic congestion syndrome
      caused by dilated ovarian veins.
AB  - OBJECTIVE: To evaluate the efficacy of multi-detector row CT (MDCT) on pelvic
      congestion syndrome (PCS), which is often overlooked or poorly visualized with
      routine imaging examination. MATERIALS AND METHODS: We evaluated the MDCT
      features of 40 patients with PCS (mean age, 45 years; range, 29-60 years) using
      axial, coronal, sagittal, 3D volume-rendered, and Maximum Intensity Projection
      MIP images. RESULTS: MDCT revealed pelvic varices and ovarian vein dilatations in
      all patients. Bilateral ovarian vein dilatation was present in 25 patients, and
      15 patients had unilateral dilatation. While 12 cases of secondary pelvic varices
      occurred simultaneously with a retroaortic left renal vein, 10 cases were due
      solely to a mass obstruction or stenosis of venous structures. CONCLUSION: MDCT
      is an effective tool in the evaluation of PCS, and it has more advantages than
      other imaging modalities.

PMID- 25610143
TI  - Treatment Results of Patients With Lupus Nephritis: A Single Center's Experience.
AB  - OBJECTIVE: Lupus nephritis (LN) is a type of organ involvement of systemic lupus
      erythematosus (SLE) that leads to disease-related morbidity and mortality. Lack
      of good treatments for LN continues to be problematic. Many different treatment
      protocols are applied in treatment centers. Not every treatment protocol is
      successful. Moreover, patients who reached remission may present with
      exacerbations. In this study, we aimed to evaluate the treatment results of our
      patients and investigate their remission rates as well as factors that affect
      remissions. MATERIALS AND METHODS: We retrospectively investigated the results of
      41 patients who were diagnosed with lupus nephritis after kidney biopsy in the
      Nephrology and Immunology-Rheumatology departments of Ataturk University Medical
      Faculty Training Hospital between January 2000 and December 2008. Demographic
      information, clinical history and laboratory results were collected from each
      patient's records. The relationships among clinical, laboratory, demographic
      parameters and remissions were investigated. The patients were grouped in terms
      of urine protein levels; patients with urine protein < 330 mg/day were regarded
      as in remission and patients with urine protein >= 330 mg/day were were regarded
      as uncontrolled. RESULTS: At the end of a 12-month period of therapy, 24 (58.5 %)
      of the patients were in remission. There were no statistically significant
      relationships among age, sex, anti-ds-DNA, C3, C4, activity indexes, chronicity
      indexes, serum level of creatinine, urine protein levels and remission (p>0.05).
      We compared class 3 LN patients at the 6th and 12th months according to treatment
      protocols. Azathioprin or mycophenolate mophetil were significantly better at
      placing urine protein levels in remission as compared to cyclophosphamide
      (p<0.05). CONCLUSION: According to our study, no relationship was found between
      basal clinical and laboratory parameters and patient remission. Response rates of
      our LN patients were similar to those in the literature. However, complete
      remission is still a problem in LN. The results of the protocols used in the
      treatment of LN show similarities. Although there are some data suggesting that
      MMF used in recent years is effective, it should be supported by prospective
      multicenter studies. It is important to note that it is difficult to achieve
      complete remission in LN patients.

PMID- 25610144
TI  - The effects of dexmedetomidine on ischemia reperfusion injury in patients
      undergoing arthroscopy under spinal anesthesia.
AB  - OBJECTIVE: Ischemia and reperfusion injury due to tourniquet application during
      arthroscopy is a well known problem. This study aimed to compare the effects of
      dexmedetomidine and ketamine on hemodynamic and respiratory variables and on
      total anti-oxidant status (TAS), total oxidant status (TOS) and malondialdehyde
      (MDA) as markers of ischemia-reperfusion injury. MATERIALS AND METHODS: This
      study was approved by a local ethics committee. The study was performed on
      patients undergoing arthroscopic operation under spinal anesthesia. Thirty
      patients were randomized into two groups: Group D (dexmedetomidine; n=15) and
      Group K (Ketamine; n=15). Spinal anesthesia at the L2-4 level was achieved using
      a 25G spinal needle with hyperbaric bupivacaine at a dose of 12-15 mg in all
      patients. In Group D, patients were sedated with dexmedetomidine at a dose of 0.3
      0.5 MUg/kg/h, while Group K received ketamine at a dose of 1-1.5 mg/kg/h.
      Hemodynamic parameters, oxygen saturation, Ramsey sedation scale (RSS), and TAS,
      TOS, and MDA levels were recorded. RESULTS: Demographic parameters, TAS, TOS and
      MDA levels were similar between groups. In Group K, the TOS levels after
      tourniquet removal were significantly lower than at baseline and during the use
      of the tourniquet. Preoperative hemodynamic and respiratory variables were
      similar in both groups. Blood pressure values were decreased compared to baseline
      but these decreases were not statistically significant. CONCLUSION: In patients
      undergoing arthroscopy under spinal anesthesia, dexmedetomidine had effects
      similar to ketamine, led to insignificant alterations in hemodynamic and
      respiratory variables during surgery and had comparable effects on ischemia
      reperfusion injury. Thus, we think that dexmedetomidine can be a safe alternative
      to ketamine as an intraoperative sedative.

PMID- 25610146
TI  - Acute respiratory insufficiency due to peripartum cardiomyopathy after caesarean
      section in a term pregnancy with twins.
AB  - We report a case of acute respiratory insufficiency due to peripartum
      cardiomyopathy after Caesarean section in a term pregnancy with twins. The
      patient was a 30-year-old woman with a spontaneous twin pregnancy at 32 weeks of
      gestation who was admitted to our obstetrics department with preterm premature
      rupture of membranes. After 48 hours, the tocolysis was stopped and an uneventful
      Caesarean was performed under general anesthesia. As the patient was waking up,
      her SPO2 decreased to 32%, and she became cyanotic and tachypneic. Auscultation
      revealed rales in her lower lung lobes bilaterally. Her oxygen saturation did not
      increase in the hours that followed, and her cyanosis persisted, so we decided to
      admit her to the Intensive Care Unit. She was mechanically ventilated. Her chest
      X-ray showed an enlarged cardiac silhouette and pulmonary infiltrates in the
      lower lobes. On the second postoperative day, transthoracic echocardiography was
      performed and revealed an EF of 45%, mild left ventricular systolic dysfunction
      and moderate mitral valve failure. Lisinopryl and furosemide were started. On
      postoperative day four, her symptoms and radiological signs had resolved. She was
      weaned from mechanical ventilation and discharged from the obstetric ward on
      postoperative day seven. 

PMID- 25610145
TI  - Sigmoid volvulus.
AB  - In sigmoid volvulus (SV), the sigmoid colon wraps around itself and its
      mesentery. SV accounts for 2% to 50% of all colonic obstructions and has an
      interesting geographic dispersion. SV generally affects adults, and it is more
      common in males. The etiology of SV is multifactorial and controversial; the main
      symptoms are abdominal pain, distention, and constipation, while the main signs
      are abdominal distention and tenderness. Routine laboratory findings are not
      pathognomonic: Plain abdominal X-ray radiographs show a dilated sigmoid colon and
      multiple small or large intestinal air-fluid levels, and abdominal CT and MRI
      demonstrate a whirled sigmoid mesentery. Flexible endoscopy shows a spiral
      sphincter-like twist of the mucosa. The diagnosis of SV is established by
      clinical, radiological, endoscopic, and sometimes operative findings. Although
      flexible endoscopic detorsion is advocated as the primary treatment choice,
      emergency surgery is required for patients who present with peritonitis, bowel
      gangrene, or perforation or for patients whose non-operative treatment is
      unsuccessful. Although emergency surgery includes various non-definitive or
      definitive procedures, resection with primary anastomosis is the most commonly
      recommended procedure. After a successful non-operative detorsion, elective
      sigmoid resection and anastomosis is recommended. The overall mortality is 10% to
      50%, while the overall morbidity is 6% to 24%. 

PMID- 25610147
TI  - Dengue Fever presenting as acute pancreatitis.
AB  - A 56-year-old non-alcoholic male was admitted with complaints of severe abdominal
      pain and was diagnosed with acute pancreatitis after blood investigations and a
      computed tomography scan of the abdomen. He developed a high-grade fever on the
      third day of admission, and serology tested positive for dengue. Treatment for
      dengue was instituted, leading to a good response and complete resolution of
      pancreatitis. The patient has been doing well and has had no recurrence of
      pancreatitis at the end of one year of follow-up. 

PMID- 25610148
TI  - Transcatheter embolization for the treatment of both vaginal and lower intestinal
      bleeding due to advanced pelvic malignancy.
AB  - We report a 31-year-old woman with end-stage cervical carcinoma who suffers both
      lower intestinal and vaginal bleeding. A selective internal iliac arteriogram
      demonstrated pseudoaneurysm formation in the vaginal branch of the left internal
      iliac artery. There was also a fistula between the pseudoaneurysm and the lower
      intestinal segments. Selective transcatheter coil embolization was performed, and
      the bleeding was treated successfully. We conclude that the internal iliac artery
      should be evaluated first in patients with advanced pelvic malignancy when
      searching for the source of lower gastrointestinal (GI) bleeding. Additionally,
      transcatheter arterial embolization is a safe and effective treatment technique. 

PMID- 25610149
TI  - Guillain-barre syndrome during active brucellosis.
AB  - It has been reported that approximately two thirds of patients diagnosed with
      Guillain-Barre syndrome (GBS) have had a prodromal illness within a four-week
      period preceding the onset of GBS. This prodromal illness is most commonly an
      upper respiratory tract illness or, secondly, gastroenteritis. However, specific
      infectious agents, such as mycoplasma, cytomegalovirus, Ebstein-Barr virus,
      vaccinia, variola, campylobacter, varicella-zoster, measles, mumps, hepatitis A
      and B viruses, rubella, influenza A and B viruses, coxackie and echoviruses, have
      also been reported to be certain or probable etiologic antecedent agents of GBS.
      In contrast, GBS during active brucellosis has rarely been reported. This article
      presents the case of a 28 year-old male patient with GBS during active
      brucellosis who responded fully to treatment directed to brucellosis. and it is
      stressed that brucellosis should be considered as a probable etiologic agent in
      patients with GBS who live in areas where brucellosis is endemic. 

PMID- 25610150
TI  - Locally invasive primary splenic angiosarcoma.
AB  - Primary angiosarcoma of the spleen is a very rare vascular neoplasm, but it
      represents the most common non-hematolymphoid malignant tumor of the spleen. In
      this report, we present the case of a 48-year-old man with primary splenic
      angiosarcoma with local invasion to the left diaphragm and the radiological
      imaging findings for this cancer. 

PMID- 25610151
TI  - Versatile use of rhomboid flaps for closure of skin defects.
AB  - OBJECTIVE: The aim of this study is to present our clinical experience with
      rhomboid flaps. MATERIALS AND METHODS: Twenty-four patients who were operated on
      between January 2006 and October 2010 were included in the study. All defects
      were reconstructed using rhomboid flaps. RESULTS: Twenty-four patients were
      operated on for various reasons, and 26 rhomboid flaps were performed. Eleven of
      the 24 cases were male, and the median age of participants was 47.5 years. Eight
      cases were operated on under general anesthesia, and 13 were locally
      anesthetized; the remaining cases were operated on under regional anesthesia. In
      17 cases, the defect was due to a benign or malignant tumor excision, and five
      cases were operated on due to burn contracture. There were no occurrences of
      partial or total flap necrosis or hematoma in our series. CONCLUSION: Our series
      indicates that rhomboid flaps can be safely used to reconstruct small to
      moderately sized skin defects.

PMID- 25610152
TI  - The significance of serum transferrin receptor levels in the diagnosis of the
      coexistence of anemia of chronic disease and iron deficiency anemia.
AB  - OBJECTIVE: Iron deficiency anemia is the most common cause of microcytic anemia
      throughout the world. Ferritin levels are good indicators of iron stores;
      however, levels may increase irrespective of iron stores in cases of chronic
      disease. Therefore, it is difficult to diagnose iron deficiency anemia coexisting
      with anemia of chronic disease. MATERIALS AND METHODS: To determine the level of
      transferrin receptor in subjects, 30 patients with iron deficiency anemia, 30
      patients with anemia of chronic disease and 30 patients with both diseases were
      included in the study. RESULTS: Mean serum transferrin receptor levels were
      5.99+/-2.98 mg/L in the iron deficiency anemia group, 1.90+/-1.15 mg/L in the
      anemia of chronic disease group and 3.07+/-0.90 mg/L in the combination group.
      Comparing groups with each other revealed significant differences (p<0.05).
      CONCLUSION: It is concluded that the assessment of serum transferrin receptor
      levels is a useful method for the diagnosis of iron deficiency anemia in
      patients.

PMID- 25610153
TI  - Conscious sedation for endoscopic retrograde cholangiopancreatography:
      dexmedetomidine versus midazolam.
AB  - OBJECTIVE: Midazolam and dexmedetomidine, which are used for sedation during
      endoscopic retrograde cholangiopancreatography, were compared to evaluate the
      differences in efficacy, hemodynamics, and side effects. MATERIALS AND METHODS:
      Fifty patients aged between 18 and 80 were randomly assigned to two groups
      according to American Society of Anesthesiologists (ASA) classification: Group M
      received midazolam with an initial bolus infusion of 0.04 mg/kg intravenously
      (i.v.), followed by additional doses of 0.5 mg i.v. midazolam, titrated to
      achieve a Ramsay sedation scale score of 3-4. Group D received dexmedetomidine
      with an initial bolus infusion of 1 mcg/kg/hr i.v. over 10 minutes, followed by a
      continuous infusion of 0.2-0.7 mcg/kg/hr, titrated to achieve an RSS of 3-4. A
      Mini Mental Status Examination (MMSE) was performed prior to sedation and in the
      recovery room once the Modified Aldrete Score (MAS) reached 9-10. Patient heart
      rates, arterial pressure and pain were evaluated. RESULTS: Patients in Group D
      had lower heart rates at 20, 25, 30, 35 and 40 minutes following the initiation
      of sedation (p<0.05). There was no statistical difference in arterial pressure,
      RSS, MMSE or respiratory rate between the two groups. Coughing, nausea and
      vomiting occurred in 3 patients in Group M (12%), whereas no patient in Group D
      experienced these symptoms. The procedure elicited a gag response in 7 patients
      in Group M (28%) and in 4 patients in Group D (16%), with no significant
      difference between groups (p>0.05). When patient and surgeon satisfaction was
      compared between the two groups, Group D showed higher surgeon satisfaction
      scores (p<0.05). CONCLUSION: The use of dexmedetomidine for conscious sedation
      during short, invasive procedures, such as endoscopic retrograde
      cholangiopancreatography, could be a superior alternative to the use of
      midazolam.

PMID- 25610154
TI  - Low serum adiponectin levels in children and adolescents with diabetic
      retinopathy.
AB  - OBJECTIVE: The aim of this study was to elucidate the role of adiponectin,
      leptin, TNF-alpha and IL-6 on the early detection of the microvascular
      complications of type I diabetes. MATERIALS AND METHODS: A total of 88 children
      were included in the study. There were 60 type I diabetic patients and 28 healthy
      control children. RESULTS: The gender, age, weight, height, BMI and puberty
      status characteristics were similar in the patient and control groups (p>0.05).
      The serum leptin, TNF-alpha and IL-6 levels were similar between the patient and
      control groups (p>0.05) and the only difference was in the serum adiponectin
      level which was higher in the patient group (p:0.042). We also found no
      association between the adiponectin, leptin, TNF-alpha and IL-6 levels and
      diabetes duration (p>0.05). Leptin was high in the pubertal period (p:0.016),
      while adiponectin TNF-alpha and IL-6 levels were similar in the prepubertal and
      pubertal periods (p>0.05). The serum leptin level was high in microalbuminuria
      patients (p<0.041). The serum adiponectin, TNF-alpha, and IL-6 levels were not
      different in patients with and without microalbuminuria (p>0.05). The serum
      adiponectin level was lower in diabetic retinopathy patients (p:0.003), while the
      serum leptin level was higher (p:0.003). The TNF-alpha and IL-6 levels were
      similar in patients with and without retinopathy (p>0.05). CONCLUSION: We found
      increased serum adinopectin levels in children and adolescents with type I
      diabetes mellitus and low levels in diabetic retinopathy patients. Patients with
      low serum adiponectin levels and high leptin levels should be more closely
      monitored for chronic complication development and better metabolic control
      should be aimed for.

PMID- 25610155
TI  - Comparing early postoperative period analgesic effect of dexketoprofene
      trometamol and lornoxicam in mediastinoscopy cases.
AB  - OBJECTIVE: In this study, we aimed comparing early postoperative period analgesic
      effectiveness and the effects on opioid consumption of intravenous dexketoprofen
      and lornoxicam that are given preemptively. MATERIALS AND METHODS: Forty
      patients, planned elective mediastinoscopy, were included in this prospective
      randomized study. These patients were classified in two groups, group D for
      dexketoprofene trometamol and group L for lornoxicam, randomly. 20 minutes before
      the operation 50 mg dexketoprofene trometamol and 8 mg lornoxicam were injected
      intravenously for group D and group L respectively. In postoperative intensive
      care unit, pain scores, mean arterial pressures, heart rates and peripheric O2
      saturations of patients were recorded at 0, 10, 20, 60, 90 and 120(th) minutes.
      RESULTS: When we evaluate the VAS score of the groups, there was a significant
      decrease in group D in all measured timesstatistically compairing to group L
      (p<0.001). When both group were evaluated in itself according to 0 minute time,
      in group L there was a significant decrease at 10 minutes time (p<0.0001) but in
      group D there was not a significant decrease (p>0.05). CONCLUSION: Since
      intravenous dexketoprofen, applied preemptively, has more potent analgesic effect
      and causing less opioid consumption in early postoperative period, is better than
      intravenous lornoxicam.

PMID- 25610156
TI  - Investigating biofilm production, coagulase and hemolytic activity in Candida
      species isolated from denture stomatitis patients.
AB  - OBJECTIVE: Oral candidiasis, in the form of Candida-associated denture
      stomatitis, represents a common disease in a large percentage of denture wearers,
      and Candida albicans remains the most commonly isolated species. In this study,
      we aimed to evaluate biofilm production, coagulase and hemolytic activity of
      Candida species isolated from denture stomatitis patients. MATERIALS AND METHODS:
      This study included 70 patients (31 female, 39 male). Forty-eight of the patients
      were found to have a positive culture. A total of 48 Candida isolates
      representing five species, C. albicans (n=17), C. glabrata (n=10), C. krusei
      (n=9), C. kefyr (n=7) and C. parapsilosis (n=5), were tested. Their coagulase
      activities were evaluated by a classical tube coagulase test with rabbit plasma.
      A blood plate assay on 3% enriched sheep blood Sabouraud-dextrose agar (SDA) was
      used to determine their in vitro hemolytic activities. Biofilm production was
      determined by a visual tube method. RESULTS: Twenty-one Candida isolates
      exhibited coagulase activity, and the coagulase activities of the C. albicans
      (64.7%) isolates were higher than other species. C. albicans, C. glabrata, C.
      kefyr and C. krusei species demonstrated beta hemolysis. C. parapsilosis strains
      failed to demonstrate any hemolytic activities. Fifteen (88.0%) of the C.
      albicans strains were biofilm positive. Six (35.2%) of these strains were
      strongly positive, 8 (47.0%) C. albicans strains were moderately positive and 1
      (5.8%) C. albicans strain was weakly positive. Sixteen (51.6%) of the non
      albicans Candida strains were biofilm positive while 15 (48.3%) did not produce
      biofilms. CONCLUSION: The results of this present study indicate coagulase,
      hemolytic activity and biofilm production by Candida spp. isolated from patients
      with denture stomatitis. Investigations of these virulence factors might be
      helpful in gaining information about the possible virulence of oral Candida
      species related to denture stomatitis.

PMID- 25610157
TI  - The effects of amlodipine on the biochemical and histopathological changes in the
      rabbit ileum subjected to ischemia-reperfusion.
AB  - OBJECTIVE: The aim of this study was to determine the potential, protective
      effects of amlodipine in an experimental, ischemia-reperfusion (I/R) model in the
      rabbit small intestine. MATERIALS AND METHODS: The rabbits were divided into four
      groups: sham-operated, amlodipine (10 mg/kg) + sham-operated, I/R, and I/R +
      amlodipine (10 mg/kg) groups. An intestinal I/R model was applied to the rabbits.
      The superior mesenteric artery was occluded for 1 h with an atraumatic vascular
      clamp and then was reperfused for 2 h. Animals in the amlodipine and I/R +
      amlodipine groups received the amlodipine by oral gavage. At the end of the 2-h
      reperfusion period, the animals were sacrificed. RESULTS: Pretreatment with
      amlodipine significantly increased SOD activity and GSH levels to values close to
      those found in the serum from the I/R group. Rabbits in the I/R group showed high
      levels of serum MDA. Amlodipine pretreatment significantly reduced the serum MDA
      levels compared to the I/R group, although the MDA levels in the I/R + amlodipine
      group were still higher than in the sham-operated group. The I/R damage was
      ameliorated by amlodipine pretreatment, as evidenced by histopathological
      analysis. CONCLUSION: The present study is the first to report an attenuation of
      I/R-induced intestinal injury by the systemic administration of amlodipine.

PMID- 25610158
TI  - The effects of atypical antipsychotic usage duration on serum adiponectin levels
      and other metabolic parameters.
AB  - OBJECTIVE: Although atypical antipsychotics are well-tolerated and effective
      treatment options for schizophrenia, they have metabolic side effects, including
      weight gain and increased risk of Type II Diabetes Mellitus (DM). Adiponectin,
      produced exclusively in adipocytes, is the most abundant serum adipokine. Low
      levels of adiponectin are correlated with DM, insulin resistance and coronary
      heart disease. Usage of atypical antipsychotics may create a risk of metabolic
      syndrome. The aim of this study was to evaluate the effects of antipsychotic
      usage on parameters related to development of metabolic syndrome. MATERIALS AND
      METHODS: A total of 27 patients (n=27) (13 women and 14 men) were recruited from
      our out-patient psychiatry clinic. All patients had been treated with atypical
      antipsychotics for at least 3 months and were in remission. Patients were
      evaluated for levels of HDL (High Density Lipoprotein), LDL (Low Density
      Lipoprotein), TG (Triglyceride) total cholesterol and fasting blood glucose, body
      weight, BMI (Body Mass Index), waist circumference and serum adiponectin levels.
      RESULTS: Serum adiponectin levels were significantly lower (p:0.000) and body
      weights were significantly higher (p:0.003) in the patients who had been using
      atypical antipsychotics for longer than a year in comparison to patients who had
      been using atypical antipsychotics for one year or less. CONCLUSION: Our findings
      supported the hypothesis that the length of administration of atypical
      antipsychotics has an effect on metabolic changes. They also highlight the fact
      that when investigating metabolic changes generated by atypical antipsychotic
      effects, the length of time that the patient has been on the atypical
      antipsychotics should also be considered.

PMID- 25610159
TI  - Epidural analgesia and lactation.
AB  - Present-day mothers have an increased desire to breastfeed, but this desire has
      increased in parallel with the increased use of epidural analgesia during labor.
      Epidural anesthesia requires a high level of technical proficiency to avoid
      serious complications and should always be performed by a trained anesthetist
      using a strict aseptic technique to reduce the risk of infection. There is
      currently no consensus regarding the relationship between breastfeeding and
      epidural analgesia during labor. The purpose of this review was to evaluate the
      effect of epidural analgesia on breastfeeding. 

PMID- 25610160
TI  - Post-traumatic glioblastoma multiforme: a case report.
AB  - Malignant glioma development after trauma is a rare occurrence. We report a
      glioblastoma multiforme case that developed after a depressed skull fracture. A
      65-year-old man was admitted because of right sided hemiplegia, epilepsy and
      changes in consciousness due to a malignant glial tumor. He had been operated on
      for a left calvarial depression fracture caused by cerebral laceration thirty
      five years before. Radiologic imaging revealed a large contrast-enhanced mass
      lesion at the left frontotemporoparietal junction under the depression site. The
      patient underwent urgent surgery, and radical excision of the mass was achieved.
      The histopathologic diagnosis was a high-grade glial tumor. Although the
      possibility of a pre-existing tumor rather than a trauma-induced tumor is very
      high, the presented case suggests that traumatic cerebral lesions may also be a
      predisposing factor for the development of malignant glial tumors. 

PMID- 25610161
TI  - Coronary vasospasm secondary to 5-Fluorouracil and its management: case report.
AB  - Although rare, 5-fluorouracil (5-FU) may lead to cardiotoxicity that presents
      with angina, elevated cardiac enzymes and electrocardiogram (ECG) changes.
      Coronary vasospasm related to 5-FU is a rare clinical entity in oncological
      practice and may be seen during both bolus and protracted infusional
      administration. This toxicity is generally reversible and responds well to
      conventional anti-angina treatment following discontinuation of infusion. We
      propose that parenteral diltiazem is an effective and safe approach for the
      treatment of coronary vasospasm secondary to 5-FU infusion. We present clinical
      findings and management of a case in which coronary vasospasm occurred during the
      infusion of the 5-FU component of FOLFIRI-bevacizumab chemotherapy (CT) regimen
      given for treatment of metastatic rectal cancer. 

PMID- 25610162
TI  - A Case of Primary Postpartum Bleeding due to Vaginal Laceration after Vaginal
      Delivery: Successful Management with Transcatheter Arterial Embolization.
AB  - Postpartum hemorrhage is one of the major causes of maternal mortality. There are
      medical and surgical options to control the bleeding, some of which can impair
      future fertility. Transcatheter arterial embolization might be a useful option in
      the management of intractable postpartum bleeding before the consideration of
      more invasive and radical methods. In this report, we report a 33-year-old
      patient who presented with primary postpartum hemorrhage due to vaginal
      laceration and was eventually treated with transcatheter arterial embolization. 

PMID- 25610163
TI  - Bilateral femoral neck fracture-related hyperparathyroidism.
AB  - Bilateral femoral neck fracture is not common as unilateral femoral fracture.
      Femoral neck fracture generally occurs by the high energized traumas. Traffic
      accidents and fallings are the most common reason for this fracture kind. But
      suddenly and minor traumatic fractures is not common. Especially, in the hormonal
      and pathogenic fractures is not common. In this case minor traumatic bilateral
      femoral fracture is presented. The fracture occurs in the background of critical
      medical condition by hyperparathyroidism. It can be said chronic
      hyperparathyroidism conditions must be determined for femoral neck fracture.
      Because these patients many times fell little disturbed by this fracture,
      diagnosis can be missed many times. 

PMID- 25610164
TI  - Candida glabrata perinephric abscess.
AB  - Perinephric abscess is a rare complication of urinary tract infections, and the
      etiology is usually a gram negative bacillus. We report a case of Candida
      glabrata perinephric abscess in a patient with diabetes mellitus who had a recent
      episode of pyelonephritis that was treated with antibiotics. Percutaneous
      drainage and fluconazole treatment led to resolution of the infection. Yeast
      perinephric abscess should be considered when symptoms of acute or chronic
      urinary tract infection occur in elderly and diabetic patients, especially
      patients who are unresponsive to antibacterial therapy. The clinical course is
      sometimes insidious. Imaging (contrast-enhanced CT or MRI) is required for
      diagnosis, and drainage is indicated for successful therapy. Adjuvant antifungal
      treatment is recommended based on the results of antifungal susceptibility tests.

PMID- 25610165
TI  - Pigeon Breeder's Disease: Multi-Detector Row Computed Tomography Imaging.

PMID- 25610166
TI  - Six rare biliary tract anatomic variations: implications for liver surgery.
AB  - OBJECTIVE: The variations in the anatomy of the biliary tract need to be
      recognized in modern liver surgery. The purpose of this clinical and anatomical
      study is to describe several novel biliary tract variations and to outline their
      practical importance for liver resections and transplantations. MATERIALS AND
      METHODS: Over the previous 10 years, the anatomic variations of the bile ducts
      were examined during 600 intraoperative cholangiographies, 104 segmentectomies
      and 54 hemihepatectomies in patients with liver diseases. The intraoperative
      anatomies of the right and left hepatic ducts and the common hepatic duct
      confluence were analyzed. RESULTS: Twenty-two variations occurred in 59.5% of the
      patients. Six variations were described for the first time: an accessory right
      hepatic duct in which a cystic duct drained; a tetrafurcation from the right
      anterior hepatic duct, right posterior hepatic duct and bile ducts for Segments 2
      and 3 with aberrant bile drainage from Segment 4 into the bile duct for Segment
      8; an aberrant bile drainage from Segments 6 and 7 into the common hepatic duct;
      an accessory bile duct for Segment 6 that drained into the bile duct for Segment
      3; a tetrafurcation from the right anterior hepatic duct and the bile ducts for
      Segments 6, 3 and 2 with bile from Segment 7 draining into the bile duct for
      Segment 2; and an accessory bile duct for the left hemiliver that drained bile
      from the Type 4 small accessory hepatic lobe (according to Caygill & Gatenby)
      into the common hepatic duct. CONCLUSION: These newly described biliary tract
      variations should be recognized by liver surgeons to avoid unwanted postoperative
      complications.

PMID- 25610167
TI  - Hip structural changes and fracture risk in osteopenia and osteoporosis.
AB  - OBJECTIVE: Although bone mineral density (BMD) is an important predictor of hip
      fracture, there is a large overlap of BMD values between those who fracture their
      hips and those who do not. The aim of this study was to evaluate differences in
      the structural parameters of the hip in patients with osteopenia and osteoporosis
      in the hip region and to assess their relationship with osteoporotic fracture
      risk, age and gender. MATERIALS AND METHODS: In this observational retrospective
      study, 150 patients with osteopenia (100 postmenopausal women and 50 men >=50
      years of age) and 125 patients with osteoporosis in the hip (100 postmenopaussal
      women and 25 men >=50 years of age) were included. In addition to densitometry
      measurements by DEXA (Dual Energy X-ray Absorbimetry), structural variables were
      determined using the Hip Strength Analysis program (HSA). RESULTS: In logistic
      regression analyses, the femoral neck BMD (odds ratio (OR), 2.6; 95% Confidence
      Interval (CI) 1.8-3.8), age (OR per 10 years 1.4; 95% CI, 1.1-1.9), femoral neck
      shaft angle (NSA) (OR 1.5; 95% CI, 1.2-2.1), Femur Strength Index (FSI) (OR 1.6;
      95% CI 1.3-2.2), and Cross sectional area (CSA) (OR 1.6; 95% CI 1.2-2.1) were all
      associated with osteoporotic fractures in women and men. Osteopenic patients had
      smaller femoral neck-shaft angles (NSA) compared to osteoporotic patients
      (p<0.05). This angle was larger in women (p<0.05); and women had decreased (FSI)
      (p<0.001) and CSA (p<0.05), which cause increased fracture risk. CONCLUSION:
      Spatial distribution of bone tissue is a useful determinant of fracture risk.

PMID- 25610168
TI  - Trace element levels in patients with familial mediterranean Fever.
AB  - OBJECTIVE: Although the genetic etiology of familial Mediterranean fever (FMF) is
      known, limited information is available regarding the regulation of inflammation
      during attack-free periods. The aim of this study was to determine the
      alterations in serum copper (Cu), zinc (Zn) and selenium (Se) levels that may be
      associated with inflammation during attack-free periods in FMF patients.
      MATERIALS AND METHODS: This study included 33 patients with FMF and 30 healthy
      volunteers. Erythrocyte sedimentation rate (ESR), the serum C-reactive protein
      (CRP) level and serum levels of Cu, Zn and Se in FMF patients and healthy
      volunteers were assessed by the atomic absorption spectrophotometry method.
      RESULTS: ESR and serum CRP levels and serum Cu and Zn levels were similar between
      patients with FMF during an attack-free period and healthy controls (p>0.05).
      Serum Se levels in the patient group were significantly higher than in the
      control group (p<0.05). CONCLUSION: Our study shows that levels of trace elements
      in serum are variable in patients with FMF during attack-free periods. Serum Se
      concentrations may at least in part contribute to the subclinical inflammation in
      FMF patients during attack-free periods. However, further studies are necessary
      to confirm this result.

PMID- 25610169
TI  - Prognostic significance of antithrombin activity in patients with crimean-congo
      hemorrhagic Fever.
AB  - OBJECTIVE: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral
      hemorrhagic fever. Disseminated intravascular coagulation (DIC) is an important
      complication of this disease, especially in severe and fatal cases. Antithrombin
      (AT) acts as an anticoagulant by inactivating thrombin, Factor IX, Factor X and
      Factor XI. We conducted this study to investigate the AT levels and their
      prognostic value in CCHF. MATERIALS AND METHODS: Twenty-eight confirmed CCHF
      patients were included in this study. Diagnosis of the disease was made by CCHF
      IgM and/or PCR positivity. Patients were grouped based on the severity criteria
      described previously. The patients with platelet counts <20 000*10(6) cell/L,
      white blood counts >10*10(9) cell/L, prothrombin times >60 seconds, aspartate
      aminotransferase levels >700 IU/L or alanine aminotransferase levels >900 IU/L
      were accepted as severe cases. Patients whose illnesses were self-limited and who
      did not require blood component replacement were accepted as mild cases, and
      patients who improved but required blood component replacement were accepted as
      moderate cases. Blood samples were obtained on the day that the patient had the
      lowest platelet count and before any thrombocyte replacement. The antithrombin
      activity was measured using a chromogenic substrate test (Diagnostica Stago STA
      Compact) at a research laboratory. RESULTS: Twenty-two (78.6%) of the cases were
      mild, 3 (10.7%) were moderate, and 3 were (10.7%) severe. The mean AT value was
      101% for mild cases, 116.6 % for moderate cases, and 88% for severe cases
      (p>0.05). Although there were no statistically significant differences between
      the AT values, the mean AT activity was lower in severe CCHF cases. CONCLUSION:
      The AT activity may have been decreased in severe CCHF cases. Further studies
      with greater numbers of patients are required to determine the level of AT
      activity and its correlation with disease severity and the prognosis of CCHF.

PMID- 25610170
TI  - Comparison of nosocomial candidemia of pediatric and adult cases in 2-years
      period at a Turkish university hospital.
AB  - OBJECTIVE: Although there are limited numerous reports of candidemia in adults,
      data on paediatrics are stil limeted. The aim of the present study was to compare
      the aetiology and risk factors of nosocomial candidemia among the paediatric and
      adults in our hospital. MATERIALS AND METHODS: This study includes the patients
      hospitalised and diagnosed as fungemia at Ondokuz Mayis University Hospital
      between June 30, 2007 and June 30, 2009 whose blood cultures sent to our
      microbiology laboratory. After fungal growth was observed in blood cultures, the
      yeast cells were inoculated onto Saboraud glucose agar. The colonies were
      identified by conventional yeast identification methods and ID 32C yeast
      identification system according to the manifacturer's instructions. RESULTS:
      During this period 51 paediatric and 69 adults were studied. The most common
      yeast form was Candida albicans (43.3%) followed by C. parapsilosis (25.0%) and
      C. tropicalis (17.5%). Although the non-albicans Candida species represent more
      than half (56.7%) of all candidemic cases C. albicans was the most common
      frequent etiologic agent. There was no statistically significant difference
      between patient age (paediatric and adult) and distribution of Candida species
      (p>0.05) Neoplasia (in adults) and prematurity (in paediatrics) were the main
      underlying diseases. Predisposing factors and mortality rates were not different
      among paediatrics and adults. CONCLUSION: We reinforce the necessity of continous
      epidomiologic surveillance to follow the dynamics of candidemia.

PMID- 25610171
TI  - Comparison of the coaxial circle circuit with the conventional circle circuit.
AB  - OBJECTIVE: The coaxial circle system helps prevent heat loss during surgery, and
      it also acts as a humidifier. This study aimed to compare the coaxial breathing
      system and the conventional system in their ability to warm and moisturize
      inhaled gases, and we also analyzed lung function protection and saccharin
      clearance time in patients who underwent tympanomastoidectomy (TMT) with the aid
      of these two systems. MATERIALS AND METHODS: Forty adult patients of ASA physical
      status I-II were scheduled for elective TMT. A standard volume-dependent
      ventilator setting was used to establish normocapnia. The coaxial circle system
      was used in the treated group (n=20), whereas the conventional circuit system was
      used in the control group (n=20). Saccharin clearance, VC (vital capacity), FRC
      (functional residual capacity), FEV1 (forced expiratory volume in 1 second),
      airway pressure, relative humidity and temperature of inspired gas, body
      temperature and adverse and hemodynamic effects were measured at different
      perioperative periods. RESULTS: The relative humidity (mg H2O Lt -1) of inspired
      gas in the treated group was higher than in the control group at 5, 15, 30, 45,
      60 and 90 minutes after anesthesia induction. The temperature of inspired gas
      (Centigrade) in the treated group was higher than in the control group (p<0.05)
      after 5, 10, 15, 30, 45, and 90 minutes of anesthesia. Postoperative saccharin
      clearance time was lower than before the operation in the treated group (p<0.05).
      Postoperative FRC was lower than preoperative FRC in the study and control groups
      (p<0.05). CONCLUSION: The coaxial circle system decreased postoperative saccharin
      clearance time and increased postoperative FRC, relative humidity and the
      temperature of inspired fresh gas, without any adverse perioperative effects in
      patients who underwent TMT.

PMID- 25610172
TI  - Serum cytokine levels and anxiety and depression rates in patients with alopecia
      areata.
AB  - OBJECTIVE: Alopecia areata (AA) is a disease characterized by patchy hair loss.
      Although the etiopathogenesis of AA is still unclear, it has been hypothesized
      that immune system dysfunction and stress are involved. The aim of this study was
      to evaluate possible associations between AA and depression, anxiety and serum
      levels of cytokines interleukin (IL)-1beta, IL-6, IL-8 and IL-10. MATERIALS AND
      METHODS: Forty-three patients who were diagnosed with AA were prospectively
      enrolled into the study. Thirty age- and sex-matched healthy individuals were
      included as the control group. The Hamilton Rating Scale for Depression and the
      Hamilton Rating Scale for Anxiety were used. For children between the ages of 7
      and 16, the Children's Depression Inventories was completed. Serum levels of the
      cytokines IL-1 beta, IL-6, IL-8, and IL-10 were analyzed by ELISA. RESULTS: No
      significant differences were observed between patients and controls with respect
      to serum cytokine levels (p>0.05). Depression rates were found to be 50% and 30%
      in AA patients and controls, respectively (p<0.05). Similarly, anxiety rates were
      found to be 63% and 23.3% in AA patients and controls, respectively (p<0.05).
      CONCLUSION: Depression and anxiety were found more frequent in AA patients than
      healthy individuals. Therefore, when considering management therapy, an entire
      psychiatric evaluation should also be performed. However, no differences were
      found in serum cytokine levels of patients and controls.

PMID- 25610173
TI  - Comparison of two different doses of intrathecal levobupivacaine for
      transurethral endoscopic surgery.
AB  - OBJECTIVE: To evaluate the effects of two different spinal isobaric
      levobupivacaine doses on spinal anesthesia characteristics and to find the
      minimum effective dose for surgery in patients undergoing transurethral resection
      (TUR) surgery. MATERIALS AND METHODS: Fifty male patients undergoing TUR surgery
      were included in the study and were randomized into two equal groups: Group LB10
      (n=25): 10 mg 0.5% isobaric levobupivacaine (2 ml) and Group LB15 (n=25): 15 mg
      0.75% isobaric levobupivacaine (2 ml). Spinal anesthesia was administered via a
      25G Quincke spinal needle through the L3-4 intervertebral space. Sensorial block
      levels were evaluated using the 'pin-prick test', and motor block levels were
      evaluated using the 'Bromage scale'. The sensorial and motor block
      characteristics of patients during intraoperative and postoperative periods and
      recovery time from spinal anesthesia were evaluated. RESULTS: In three cases in
      the Group LB10, sensorial block did not reach the T10 level. Complete motor block
      (Bromage=3) did not occur in eight cases in the Group LB10 and in five cases in
      the Group LB15. The highest sensorial dermatomal level detected was higher in
      Group LB15. In Group LB15, sensorial block initial time and the time of complete
      motor block occurrence were significantly shorter than Group LB10. Hypotension
      was observed in one case in Group LB15. No significant difference between groups
      was detected in two segments of regression times: the time to S2 regression and
      complete sensorial block regression time. Complete motor block regression time
      was significantly longer in Group LB15 than in Group LB10 (p<0.01). CONCLUSION:
      Our findings showed that the minimum effective spinal isobaric levobupivacaine
      dose was 10 mg for TUR surgery.

PMID- 25610174
TI  - Benefits of estrogen replacement for skeletal muscle mass and function in post
      menopausal females: evidence from human and animal studies.
AB  - Age related loss of skeletal muscle mass and strength accelerates with the onset
      of menopause in women. Recent evidence from human and animal studies provides
      compelling evidence for the role of estrogen based hormone replacement therapy
      (HRT) in maintaining and enhancing muscle mass and strength and protecting
      against muscle damage. The physiological mechanisms by which estrogen can
      positively influence skeletal muscle mass and strength and protect against post
      damage inflammation and disruption are also beginning to emerge. These less well
      known benefits of estrogen for skeletal muscle coupled with other benefits of
      estrogen to bone and metabolic health in older females provide further incentives
      for HRT use to enhance overall health in post-menopausal women. New research also
      attests to the safety of shorter term HRT in younger post-menopausal females.
      Overall the benefits of HRT to muscle health and function could assist in
      offsetting age related loss of muscle mass and function and delay age related
      morbidity and their use for overall health benefits in aging females should
      continue to be evaluated. 

PMID- 25610175
TI  - Hyperthermia in the treatment of post-actinic osteosarcomas: our anecdotal
      experience.
AB  - Irradiation-induced sarcomas are a late sequelae of irradiation therapy. Most
      sarcomas have been reported to occur after exposure to a radiation dose of 55 Gys
      and above, with a dose ranging from 16 Gys to 112 Gys. These tumours are very
      aggressive and an early detection is needed for a timely intervention. Surgery is
      only effective treatment for local control instead chemotherapy is a valuable
      tool for systemic control of disease. Irradiation therapy use is controversial
      because of its side effects on a site previously irradiated. Irradiation therapy
      combined with hyperthermia is a new treatment that overcomes these problems
      without limiting the effect of radiation therapy. It may become a tool for local
      control of the unresectable tumours or an adjuvant treatment of the surgery. In
      this report we present a rare case of irradiation-induced recurrent osteosarcoma
      involving the chest wall that was treated with surgical resection followed by
      radiation therapy combined with hyperthermia as an adjuvant treatment of the
      surgery. 

PMID- 25610176
TI  - A Mild Chest Trauma in an Infant who Developed Severe Pulmonary Hemorrhage.
AB  - Chest trauma, an important cause of morbidity and mortality, is the second most
      common cause of death in children under four years of age. Due to the different
      anatomy and physiology of the respiratory system in childhood, the injuries and
      consequences of chest trauma are also dissimilar. A seven-month-old male infant
      presented to the emergency clinic with cyanosis and respiratory distress. His
      medical history revealed that he had been found trapped behind his bed in a
      cyanotic state two hours earlier. Although physical examination revealed no signs
      of trauma, respiratory distress and hemorrhagic secretions indicated pulmonary
      hemorrhage or contusion. This preliminary diagnosis was confirmed by thoracic
      tomography. There was complete recovery following 48-hour oxygen and medical
      treatment. Even after mild injuries, the fact that severe pulmonary hemorrhages
      and contusions may develop without a trace of trauma should be kept in mind. 

PMID- 25610177
TI  - Hypertrygliceridemia-induced Acute Pancreatitis Following Hyperlipidemic
      Abdominal Crisis.
AB  - Hypertriglyceridemia is a well established cause of acute pancreatitis (AP).
      Multiple mechanism are proposed to explain this phenomenon, but the exact
      mechanism is unknown. Clinical manifestations are similar to other forms of AP.
      Although amylase and lipase levels exclude the diagnosis of AP in normolipidemic
      patients, they may be normal in hypertriglyceridemia-induced AP. Further
      evaluation with imaging studies are needed for diagnosis. A less known entity
      "hyperlipidemic abdominal crisis" is a prior clinical state before development to
      AP. We describe a young male patient without any previously diagnosed metabolic
      disorder presenting to emergency department with abdominal pain and vomiting
      where normal amylase in lactescent serum was detected. His abdomen computed
      tomography (CT) was reported as normal. His symptoms were relieved with
      antiemetic and histamine-2 blocker and he was diagnosed with hypertriglyceridemia
      and dyspepsia. Readmission with recurrence of symptoms after 3 hours resulted in
      hospitalization where the second CT showed edematous AP. 

PMID- 25610178
TI  - ST Elevation Myocardial Infarction Due to Carbon Monoxide Poisoning.
AB  - Carbon monoxide is formed as a result of combustion of any carbon compound and
      can lead to hypoxia in many organs including the brain and the heart. Carbon
      monoxide poisoning in the United States is the leading cause of the fatal
      poisonings. In this study we present a case with no-known accompanying disease in
      the light of literature where myocardial infarction was developed as a result of
      carbon monoxide poisoning. 

PMID- 25610179
TI  - May-thurner syndrome: a case report.
AB  - May-Thurner Syndrome (MTS) or iliac vein compression syndrome is caused by
      compression of the left common iliac vein by the right common iliac artery. This
      obstruction may cause leg swelling, varicosities, deep venous thrombosis, chronic
      venous stasis ulcers, or more serious complications, such as pulmonary embolism.
      Iliac vein compression can be assessed with computed tomography (CT) and iliac
      venography. The goals of treatment are to reduce symptoms and to reduce the risk
      of complications. Stent placement is an alternative method to a direct surgical
      approach. We present a case of MTS, treated with stent placement. 

PMID- 25610180
TI  - A blue-domed cyst of bloodgood.

PMID- 25610181
TI  - Fundoplication after heller myotomy: a retrospective comparison between nissen
      and dor.
AB  - OBJECTIVE: A retrospective comparison between Nissen and Dor fundoplication after
      laparoscopic Heller myotomy for achalasia. MATERIALS AND METHODS: From 1998 to
      2004 a first group of 48 patients underwent Heller myotomy and Nissen
      fundoplication for idiopathic achalasia (H+N group). From 2004 to 2010 a second
      group of 40 patients underwent Heller myotomy followed by Dor fundoplication (H+D
      group). Some patients received a previous endoscopic treatment with pneumatic
      dilatation or endoscopic injection of botulinum toxin that provided them only a
      temporary clinical benefit. Changes in clinical and instrumental examinations
      from before to after surgery were evaluated in all patients. Clinical evaluation
      was carried out using a modified DeMeester symptom score system. RESULTS: Dor
      fundoplication treatment reduced both dysphagia and regurgitation severity scores
      significantly more than Nissen fundoplication (p<0.0001). Indeed, the incidence
      of dysphagia was significantly higher in patients treated with floppy-Nissen than
      in those treated with Dor fundoplication: by defining dysphagia as a DeMeester
      score equal to 3 (arbitrary cut-off), at the end of follow-up dysphagia occurred
      in 17.65% and 0% (p=0.037) of patients belonging to the H+N and H+D groups,
      respectively. CONCLUSION: Heller myotomy followed by Dor fundoplication is a safe
      and valuable treatment. The procedure showed a lower incidence of postoperative
      dysphagia versus Nissen fundoplication and a negligible incidence of
      postoperative GERD in a long-term postoperative follow-up.

PMID- 25610182
TI  - Metabolic syndrome and neurotrophins: effects of metformin and non-steroidal
      antiinflammatory drug treatment.
AB  - OBJECTIVE: Metabolic syndrome (MS) presents with central obesity, impaired
      glucose metabolism, dyslipidemia and hypertension. Our aim was to examine the
      effect of metformin treatment either alone or in combination with non-steroidal
      anti-inflammatory drugs (NSAID) on plasma levels of nerve growth factor (NGF) and
      brain-derived neurotrophic factor (BDNF) in patients with early stage MS (MS-es)
      and generalized MS (MS-ge). MATERIALS AND METHODS: The study compared 35 female
      patients with MS-es (mean age of 43.39+/-1.54 years) and 40 patients with MS-ge
      (mean age of 45.69+/-2.18 years) to 10 age-matched controls each. Patients with
      MS-es were administered 850 mg metformin twice daily. The patients with MS-ge
      were divided into two groups of 20 patients per group. One group received
      metformin alone, while the other group received metformin in combination with 500
      mg aspirin and 150 mg Diclac daily. Plasma NGF and BDNF levels were measured by
      ELISA. Statistical data analysis was performed using ANOVA. RESULTS: Plasma NGF
      and BDNF levels were significantly higher in MS-es patients and lower in MS-ge
      patients than in controls. NGF levels were decreased in both groups after
      treatment with metformin. NGF levels were significantly higher in MS-ge patients
      on combined therapy than in those on metformin only. CONCLUSION: The combination
      of metformin and NSAID treatment is more effective than metformin alone on NGF
      and BDNF production as well as on metabolism-related anthropometric and
      laboratory features. This represents a pathogenetic therapeutic mechanism in MS
      due to its strong anti-inflammatory effect and improves MS-ge symptoms.

PMID- 25610183
TI  - Relationship between meniscal tears and tibial slope on the tibial plateau.
AB  - OBJECTIVE: The geometry of the tibial plateau has a direct influence on the
      translation and the screw home biomechanics of the tibiofemoral joint. Little
      information on the relationship between the tibial slope and meniscal lesions is
      available. The objective of this retrospective study was to examine the effect of
      the tibial slope on the medial and lateral meniscus lesions in patients with
      intact ACLs. MATERIALS AND METHODS: The MRIs and lat roentgenograms of 212
      patients with meniscus lesions were examined to determine the possible effect of
      the tibial slope on meniscal tears. First, the anatomic axis of the proximal
      tibia was established. Then, the angle between the line drawn to show the tibial
      slopes (medial and lateral) and the line drawn perpendicular to the proximal
      tibial anatomic axis was established on MRI. The patients with previously
      detected meniscus lesions were classified into three categories: patients with
      only medial meniscal tear (Group 1, 90 patients); patients with only lateral
      meniscal tear (Group 2, 15 patients); and patients with both medial and lateral
      meniscal tear (Group 3, 19 patients). Group 4 had no meniscal tear (88 patients).
      The MRIs of the patients who had applied to the Orthopedic Outpatient Clinic with
      patellofemoral pain and no meniscal tear were included as the control group.
      RESULTS: The average tibial slope of the medial tibial plateau was 3.18 degrees 
      in group 1, 3.64 degrees  in group 2, 3 degrees  in group 3, and 3.27 degrees  in
      group 4. The average tibial slope of the lateral tibial plateau was 2.88 degrees 
      in group 1, 3.6 degrees  in group 2, 2.68 in group 3, and 2.91 in group 4. The
      tibial slope on the medial tibial plateau was significantly larger than the
      lateral tibial plateaus in group 1 and group 4 (p<0.05). In group 2, there was no
      statistically significant difference between the tibial slopes of the two sides
      (p>0.05). In addition, the tibial slope on the lateral side of group 2 was
      significantly larger than that of groups 1, 3, and 4 (p<0.05). CONCLUSION: An
      increase in the tibial slopes, especially on the lateral tibial plateau, seems to
      increase the risk of meniscal tear.

PMID- 25610184
TI  - Compared with the Conventional MR Imaging, Do the Constructive Interference
      Steady State Sequence and Diffusion Weighted Imaging Aid in the Diagnosis of
      Lumbar Disc Hernias?
AB  - OBJECTIVE: Our aim was to evaluate the efficacy of Diffusion Weighted Imaging
      (DWI) and Constructive Interference Steady State (CISS) sequences in the
      depiction of lumbar disc hernias, including sequestrated and extruded discs.
      MATERIALS AND METHODS: 100 patients; 35 males and 65 females, with 3
      sequestration-16 extruded and 81 protruded all together 100 herniated discs were
      involved in this study. If a patient had more than one herniated disc, then the
      more precise herniation was included. All the MRI procedures were handled in
      Siemens Symphony Power 1.5 T. magnet. DWI- Apparent diffusion coefficient (ADC
      mapping) and CISS sequences were obtained in axial planes. Statistical analysis
      of CISS and DWI results were analysed by fischer's test, chi square statistics.
      RESULTS: CISS sequence had a 89% sensitivity, 100% specificity for all lumbar
      disc hernias, had 100% sensitivity and specificity in the evaluation of
      sequestrated and extruded discs. DWI had a 77% sensitivity and %100 specificity,
      had 100% sensitivity and 50% specificity in the evaluation of extrusion, 100%
      sensitivity and specificity in the evaluation of sequestration. CONCLUSION: CISS
      sequence and quantitative DWI may be alternative imaging modalities to the
      routine MR imaging sequences in the depiction of lumbar disc hernias, including
      sequestration and extruded discs.

PMID- 25610185
TI  - A study on the complications of surgical treatment for bilateral developmental
      dysplasia of the hip and a comparison of two osteotomy techniques.
AB  - OBJECTIVE: This study aims to present a review about complications of surgical
      treatment of Developmental Dysplasia of the Hip and comparing the kinds and
      ratios of two osteotomy technique (Salter Innominate Osteotomy and Pemberton
      Pericapsular Osteotomy). MATERIALS AND METHODS: Fifty-seven patients of 126 that
      had bilateral developmental dysplasia of the hip are the case series that had
      undewent to Salter Innominate Osteotomy for one hip and Pemberton Pericapsular
      Osteotomy for other hip by one surgeon in one stage. RESULTS: Avascular Necrosis
      ratio was 19.29% on hips with Salter Innominate Osteotomy, and 8.77% on hips with
      Pemberton Pericapsular Osteotomy. Salter Innominate Osteotomy made lower limb
      discrepency with 0.47 cm mean in all patients. There were 17 general
      complications on hips with Salter Innominate Osteotomy (SIO) (14.91%) and 9
      general complications on hip with Pemberton Pericapsular Osteotomy (PPO) (7.89%).
      As looking for general complications, SIO/PPO ratio were 1.8 (17/9). CONCLUSION:
      By the comparing two osteotomy technique for complication ratios, SIO had two
      fold of complications than PPO. SIO had 65% more complications as to PPO.

PMID- 25610186
TI  - Antistreptolysin O Levels in Patients with Behcet's Disease.
AB  - OBJECTIVE: Behcet's disease is a multisystem inflammatory disorder, and its
      etiology has not been defined clearly yet. In this study, we aimed to investigate
      the antistreptolysin O (ASO) levels of patients with Behcet's disease. MATERIALS
      AND METHODS: Thirty patients with Behcet's disease and 30 healthy controls were
      enrolled in this study. We measured erythrocyte sedimentation rate (ESR), serum C
      reactive protein (CRP), and ASO levels in both groups. RESULTS: There was no
      statistically significant difference between the two groups with respect to
      demographic data (p>0.05). The ASO levels of the patients and the controls were
      288.4+/-145.7 and 170.6+/-142.4 ng/ml, respectively. In the patients with
      Behcet's disease, ASO (p<0.01) and ESR (p<0.05) values were significantly higher
      than in the healthy controls. There was no other significant difference in serum
      CRP levels between the patients and the controls. We could not find any
      correlation among ASO, CRP, and ESR values. CONCLUSION: Our results suggest that
      serum ASO levels may increase in patients with Behcet's disease. Further studies
      are needed in order to define the relationship between ASO levels and
      inflammation status in Behcet's disease.

PMID- 25610187
TI  - Evaluation of Peripheral Blood Smear for Myelodysplasia in Breast Cancer Patients
      who Received Adjuvant Antracycline.
AB  - OBJECTIVE: Therapy-related myeloid neoplasms (t-MN) account for approximately 10%
      to 20% of all cases of AML (acute myeloid leukemia), MDS (myelodysplastic
      syndrome) and MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasms),
      MDS, and MDS/MPN. In our study, we evaluated peripheral blood smear samples and
      hemogram values in breast cancer patients who were receiving adjuvant
      anthracycline regimens and were in remission. MATERIALS AND METHODS: A total of
      78 patients receiving anthracycline-based adjuvant chemotherapy treatment from
      Kayseri Research and Training Hospital and Mersin State Hospital were enrolled in
      the study. Their adjuvant treatments had been completed at least 18 months prior
      to the study. RESULTS: Two patients complained of anemia (2.2%) (Hb<11 mg/dl),
      leukopenia was observed in seven patients (7.7%) (leukocytes<4000/ mm(3)), and
      thrombocytopenia was observed in four patients (4.4%) (PLT<150.000/mm(3)). In the
      blood smear samples, the following were observed: ovalomacrocytes (14%),
      macrocytes (37%), acanthocytes (1%), stomatocytes (12%), teardrops (12%),
      nucleated erythrocytes (1%), basophilic stippling (14%), and Howell-Jolly bodies
      (1%). Additionally, hypo-granulation (38%), Pelger-Huet abnormalities (26%),
      hypersegmentation (20%), immature granulocytes (8%), and blasts (6%) were
      observed. We also confirmed the presence of giant platelets (50%) and platelet
      hypogranulation (19%). CONCLUSION: According to the peripheral blood smear
      assessments in our study, we suggest that breast cancer patients should be
      evaluated for MDS in the early stages, starting from month 18, even if the
      automated blood counts are normal.

PMID- 25610188
TI  - Incidence and risk factors of the secondary skin infections in patients with
      radiodermatitis.
AB  - OBJECTIVE: The aim of this prospective study was to investigate the incidence and
      risk factors of secondary infected radiodermatitis in patients receiving
      radiotherapy and to determine isolated microorganisms' resistance profiles to
      different antimicrobial agents. MATERIALS AND METHODS: The study comprised 62
      patients admitted to the Regional Training and Research Hospital from January
      2009 to January 2010. Radiodermatitis was graded according to the National Cancer
      Institute's Common Toxicity Criteria version 3.0. Potential risk factors for
      secondary infection were recorded and evaluated by univariate and multivariate
      analyses. RESULTS: In 62 patients, grade 1, 2, 3 and 4 radiodermatitis were
      observed in 33 (53.2%), 11 (17.7%), 8 (12.9%) and 10 (16.2%) patients,
      respectively. Skin infection secondary to radiodermatitis occurred in 14 patients
      (infected patients), 21.4%, 21.4% and 57.2% of whom had grade 2, 3 and 4
      radiodermatitis, respectively. Forty-eight patients were found to be colonized
      with micoorganisms (colonized patients). In the univariate analysis, concurrent
      endocrine therapy and radiodermatitis grade differed significantly between
      infected and colonized patients (p<0.05). Multivariate analyses showed that the
      radiodermatitis grade was an independent risk factor for the acquisition of
      infection (p<0.05). The microbial pathogens isolated from patients with skin
      infection were seven methicillin-resistant coagulase-negative Staphylococcus
      (MRCNS) strains, three methicillin-resistant Staphylococcus aureus (MRSA)
      strains, two Candida sp., one methicillin-sensitive coagulase-negative
      Staphylococcus (MSCNS) strain and one methicillin-sensitive S. aureus (MSSA)
      strain. Staphylococci strains were more resistant to beta-lactam antibiotics. No
      glycopeptide resistance was found. CONCLUSION: The results of this study indicate
      that high-grade radiodermatitis leads to an increased risk for secondary
      infection of the skin with pathogens.

PMID- 25610189
TI  - Glutamate transporter activators as anti-nociceptive agents.
AB  - The effective management of chronic pain remains enigmatic. There is a paucity of
      effective mechanistically-based approaches employed. Chronic visceral pain is a
      particularly difficult subcategory to manage. Glutamate is the most predominant
      excitatory neurotransmitter and mediates many aspects of sensory function
      including acute and chronic pain. There is a growing literature describing the
      efficacy of physiologically dominant glutamate transporter GLT-1 up-regulation in
      attenuating chronic visceral and somatic nociception. Since glutamate is the
      major excitatory neurotransmitter released in the first central synapse of the
      pain-transmitting afferent neurons, augmentation of GLT-1 activity, which reduces
      extracellular levels of glutamate, may be an important target for pain management
      strategies. This review summarizes studies in our laboratory and others which
      highlight findings that GLT-1 up-regulation by transgenic, pharmacologic and
      viral transfection approaches attenuate a host of nociceptive responses emanating
      from visceral or somatic sources in animal models. The study also outlines the
      future work that will be required to ascertain the translational potential of
      this approach. 

PMID- 25610190
TI  - Cases of Brainstem Infarcts after Cessation of Heparin Treatment: is it a Rebound
      Effect?
AB  - The presented cases represent patients with acute coronary syndrome treated with
      heparin infusion who developed brainstem infarction after discontinuation of
      heparin treatment. The patients did not present genetic coagulopathy. Others risk
      factors were analyzed, and the discontinuation of heparin infusion was also
      considered to have a predominant role in the development of infarction. 

PMID- 25610191
TI  - Multimodality treatment in the management of anorectal melanoma: a case report
      and review of the literature.
AB  - Anorectal melanoma represents approximately 0.2-1% of all malignant melanomas and
      has a poor prognosis, with a median survival of 8 to 23 months after the time of
      diagnosis. The typical treatment modalities include surgery, radiotherapy and
      chemotherapy. The particular approach taken depends on the patient's status and
      disease stage. Although there are different treatment options for this rare
      condition, there are not enough studies on multimodality treatment. Here, we
      present the case of a 54-year-old female with anorectal melanoma that had
      metastasized to an inguinal lymph node. She underwent local excision of the
      rectal mass and inguinal lymph-node dissection. Temozolomide treatment was
      started after radiotherapy and was given for 24 months. Follow-up revealed that
      the patient has been doing well with no signs of recurrence three years after the
      completion of treatment. We aim to discuss combined treatment modalities for ARM
      in light of the pertinent literature. 

PMID- 25610193
TI  - Nonspecific infectious bilateral chylothorax and cyhloabdomen with symptoms of
      acute abdomen.
AB  - Co-existence of chylothorax and chyloabdomen is a rare clinical entity. Apart
      from surgery and extra-surgical trauma, malignancies, liver cirrhosis, nephrotic
      syndrome, thrombosis in the superior vena cava and acute pancreatitis play roles
      in the etiology. The case presented in this article was a 35-year-old woman, and
      the chronic infectious pathology in the cytology, plus the other supportive
      nonspecific infection parameters prompted us in establishing this diagnosis.
      Obstruction in the abdominal lymphatics leads to chylous ascites and chylothorax
      develops in due course. Similar to our case, the clinical entities of chylothorax
      and chyloabdomen of nonspecific infectious origin may co-exist in the same
      patient. 

PMID- 25610192
TI  - Serious skin reaction associated with imatinib in a patient with chronic myeloid
      leukemia.
AB  - Imatinib mesylate (STI 571) is one of the fundamental chemotherapeutic agents
      used in the treatment of the chronic, accelerated and blastic phases of chronic
      myelocytic leukemia (CML), gastrointestinal stromal tumors and Philadelphia
      chromosome-positive acute lymphoblastic leukemia. It selectively inhibits
      receptor tyrosine kinases. Its effects limit the use of this drug. We present a
      case with a serious skin reaction requiring the discontinuation of the drug and
      that developed in relation to imatinib therapy. Six months prior, a 61-year-old
      male patient presenting to the hematology polyclinic with complaints of weight
      loss and sweating was hospitalized due to high leukocyte value. As a result of
      the hemogram, biochemistry analyses, peripheral blood smear examination, bone
      marrow aspiration evaluation, cytogenetic examination using FISH and PCR that
      were performed, CML was diagnosed. Additionally, to exclude myelofibrosis, we
      examined a bone marrow biopsy. Imatinib mesylate was started at 400 mg/day
      orally. In the fourth month of treatment, the patient complained of itching and a
      skin rash. Although the drug dose was reduced (300 mg/day), his complaints
      gradually increased. The skin biopsy result was superficial perivascular
      dermatitis. Imatinib was discontinued, and the patient was started on
      corticosteroid. The lesions disappeared completely. A month later, the patient
      was restarted on imatinib mesylate. However, the lesions recurred more
      prominently. His itching increased. The patient was considered intolerant to
      imatinib mesylate, and a second-generation tyrosine kinase inhibitor, dasatinib
      100 mg/day, was started orally. The follow-up and treatment continues for the
      patient, who has been taking dasatinib 100 mg/day for the last two months without
      any skin finding or complaints. Imatinib mesylate-induced skin reactions are
      associated with the pharmacologic effect of the drug rather than hypersensitivity
      to the drug. Skin reactions are frequently observed, and this side effect is dose
      dependent. However, the interesting aspect of our case was that despite dose
      reduction, skin findings gradually increased, and eventually the drug had to be
      discontinued. 

PMID- 25610194
TI  - Recurrent postpartum eosinophilic pneumonia presenting as acute respiratory
      distress syndrome.
AB  - Eosinophilic pneumonia (EP) is a rare disease of the lung. We aimed to present
      atypical course of two EP cases. They were admitted to our hospital because of
      acute respiratory distress syndrome (ARDS) in postpartum period. Eosinophilia was
      detected in bronchoscopic bronchoalveolar lavage and laboratory examination. In
      these cases, no spesific cause for eosinophilic pneumonia was determined and
      steroid treatment was started. After the treatment, the patients were in full
      recovery which were confirmed by clinical and radiological investigations,
      readmitted to our clinic with relapses of ARDS. The patients have received
      regular treatment for 1 year. Our cases were neither fitting the classic
      definitions of acute eosinophilic pneumonia nor chronic eosinophilic pneumonia.
      Therefore, we wanted to contribute additional data in the literature by sharing
      these interesting cases. 

PMID- 25610195
TI  - Pulmonary Arteriovenous Malformation (PAVM): Multidetector Computed Tomography
      Findings.

PMID- 25610196
TI  - Therapeutic drug monitoring of gentamicin in patients with bronchopneumonia: cost
      considerations and patient outcomes.
AB  - OBJECTIVE: In Malaysia, therapeutic drug monitoring (TDM) service started in the
      late 1980s. Serum concentration measurements depend on commercially available
      drug assays, which are costly. In the present study, we attempted to document the
      impact of TDM service on cost and patient outcomes. MATERIALS AND METHODS: We
      reviewed the medical records of the patients who were admitted to the hospital
      over a five-year period, diagnosed with bronchopneumonia and treated with
      gentamicin. Outcome measures were duration of fever, incidence of nephrotoxicity
      and length of hospital stay. We calculated the costs of laboratory and clinical
      investigations, the costs associated with the administration of gentamicin doses,
      the cost of providing TDM services, the costs associated with medical care by
      professional staff and the costs of hospital stays during gentamicin treatment.
      RESULTS: Sixty-six patients were found to meet the inclusion criteria (10
      patients were provided with TDM service and 56 patients were not). There was no
      significant difference in the duration of fever or the length of hospital stay
      during gentamicin therapy between the two groups. Although serum creatinine
      levels were not checked in all of the patients after gentamicin therapy, the data
      analysis did not show any cases of nephrotoxicity. There was no significant
      difference in the costs of laboratory investigations, the total cost of
      gentamicin therapy and the costs associated with professional staff between the
      two groups. The cost of the hospital stay during gentamicin therapy and the total
      cost of hospitalization were significantly higher in the TDM group. CONCLUSION:
      Evaluation in patients with bronchopneumonia shows that TDM in our setting was
      associated with higher cost; however, we did not observe any significant
      differences in the clinical outcomes.

PMID- 25610197
TI  - A Radiological Study on the Topographical Relationships between the Vestibular,
      Cochlear and Facial Nerves.
AB  - OBJECTIVE: The purpose of our study was to investigate the topographical
      relationship between these nerves along their course from the brainstem through
      the internal acoustic canal IAC in the living human brain using MR imaging.
      MATERIALS AND METHODS: We performed three-dimensional gradient echo balanced Fast
      Field Echo (3D bFFE) sequence oblique parasagittal MR imaging in 73 healthy
      subjects. The IACs were analyzed from the brainstem end of the IAC to the fundus
      in contiguous sections. At five levels, the topographical relationships between
      the facial and vestibulocochlear nerves (VCN) were recorded. In the lateral
      portions of the IACs where they separated from each other, the relative sizes of
      the individual nerves were examined. RESULTS: In general, the facial nerve (FN),
      which is a round structure, is located anteriorly and superiorly to the
      vestibulocochlear nerve throughout its course. The vestibulocochlear nerve is
      usually rectangular; however, it was found to be round and at times triangular in
      shape near the brainstem, before it became crescent-shaped at the porus in 89% of
      the cases. The superior vestibular nerve kept its posterosuperior position in the
      canal, and the inferior vestibular nerve (IVN) and the cochlear nerve (CN)
      travelled inferior to it. The superior and inferior vestibular nerves were
      divided by the falciform crest in 53% of the cases. The inferior vestibular nerve
      was the smallest nerve in 52% of the cases, and the cochlear nerve was the
      largest in 36% of the cases. CONCLUSION: To the best of our knowledge, this study
      is the largest in vivo MR study, and most of our findings differ from previous
      cadaver studies. Determination of these topographical relationships may
      facilitate our understanding of the complicated physiological relationships
      between the 7(th) and 8(th) nerve complexes during surgery in this region.

PMID- 25610198
TI  - The Correlation between Infarct Size and the QRS Axis Change after Thrombolytic
      Therapy in ST Elevation Acute Myocardial Infarction.
AB  - OBJECTIVE: Electrocardiography (ECG) may be a practical guiding tool for
      prognostic infarct sizing in ST elevation acute myocardial infarction (STEAMI).
      In this study, we sought to find a relation between the infarct size and the
      change in the QRS axis after thrombolytic therapy. MATERIALS AND METHODS:
      Patients with STEAMI who received thrombolytic therapy were selected
      retrospectively. The mean QRS axes of two ECGs (before and 90 minutes after
      thrombolytic therapy) were calculated. Creatinine kinase MB (CKMB) was used as
      the marker of infarct size. RESULTS: We did not detect any correlation between
      infarct size and change in the QRS axis with respect to any myocardial infarction
      MI localizations (p=0.80). However, in the isolated inferior MI group, there was
      a good correlation between CKMB and change in the QRS axis (r=-0.52 p=0.049).
      CONCLUSION: The change in the QRS axis is rarely emphasized, providing a
      practical and promising tool for evaluating both the efficiency of the
      thrombolytic therapy and prognostic infarct sizing.

PMID- 25610199
TI  - Neuroendoscopic approach to quadrigeminal cistern arachnoid cysts.
AB  - OBJECTIVE: The introduction of neuroendoscopy has provided a minimally invasive
      modality for the surgical treatment of quadrigeminal arachnoid cysts. Three
      pediatric patients with arachnoid cyst of the quadrigeminal cistern treated by
      endoscopic fenestration are reported. MATERIALS AND METHODS: The hospital records
      of patients were retrospectively rewieved. All patients had hydrocephalus. A
      lateral ventricle-cystostomy and endoscopic third ventriculostomy were performed
      by using rigid neuroendoscopes. RESULTS: There were one boy and two girls with
      ages 7 months, 9 months and 14 years, respectively. One patient had undergone
      shunting prior to neuroendoscopic surgery. The postoperative course was
      uneventful in all cases, with no complications. They showed disappearance of
      intracranial hypertension symptoms and significant reduction of the cyst size.
      CONCLUSION: Neuroendoscopic technique is an effective and suitable method for the
      treatment of quadrigeminal cistern arachnoid cysts and accompanying
      hydrocephalus.

PMID- 25610200
TI  - Ethnic differences in body mass index, weight and height among school children in
      the north of iran.
AB  - OBJECTIVE: Overweight and obesity are common health problems among adolescents.
      This study was set up to evaluate these problems and certain socio-demographic
      related factors among three ethnic groups as represented by primary school
      children in northern Iran in 2010. MATERIALS AND METHODS: This was a descriptive
      and cross-sectional study performed on 7433 students (Fars-native=3268,
      Turkman=2852, Sisstani=1313) from 112 schools in urban and rural areas. The
      schools and students were chosen by cluster and stratified sampling. The data
      were collected by interviewers for all samples throughout the study. Overweight
      and obesity were identified on the basis of the BMI cut-off Centers for Disease
      Control and Prevention (CDC) values (in excess of the 85(th) and 95(th)
      percentiles, respectively). SPSS 16.0 software for Windows was used for the
      analysis. RESULTS: Linear regression analyses revealed that weight, height and
      BMI increased by 2.70 kg, 4.62 cm and 0.42 kgm(-2), respectively, in boys
      (p=0.001) and 3.12 kg, 5.19 cm and 0.52 kgm(-2), respectively, in girls (p=0.001)
      for each year increase in age. In total, overweight was identified in 8.4% of
      those studied, while obesity was common in 14.1% of students. The rates of
      overweight and obesity were significantly different among all three ethnic groups
      (p=0.001). These rates were higher among the Fars-native individuals and lower
      among the Sisstani individuals as compared with the other groups. Logistic
      regression analyses showed that the risk of overweight and obesity was 2.104
      (1.769-2.502, CI: 95%)-fold greater in the Fars-native as compared with the
      Sisstanish ethnic group and 2.297 (1.911-2.761, CI 95)-fold greater in the good
      economic group as compared with the poor economic group. CONCLUSION: One out of
      seven primary school children in northern Iran suffers from obesity and
      overweight, although the rates differed among the three ethnic groups examined.
      This study emphasizes the importance of public health training about obesity for
      children, especially those living in urban areas and those from high-income
      families.

PMID- 25610201
TI  - Persistence of nosocomial pathogens on various fabrics.
AB  - OBJECTIVE: Fabrics can become contaminated with high numbers of microorganisms
      that may be pathogenic to patients in a hospital setting and can play an
      important role in the chain of infection. The aim of this study was to
      investigate the survival of several clinical bacterial and fungal isolates on
      several fabrics commonly used in hospitals. MATERIALS AND METHODS: Bacterial and
      fungal survival was tested on the following materials, each of which are commonly
      used in our hospital: 100% smooth cotton, 60% cotton-40% polyester, 100% wool and
      100% silk. One isolate each of Candida albicans, Candida tropicalis, Candida
      krusei, Candida glabrata, Candida parapsilosis, Geotrichum candidum, Aspergillus
      fumigatus, Cryptococcus neoformans, vancomycin resistant Enterococcus faecium
      (VRE, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta
      lactamase (ESBL) positive Escherichia coli, inducible beta-lactamase (IBL)
      positive Pseudomonas aeruginosa, IBL-positive Acinetobacter baumannii and
      Stenotrophomonas maltophilia were used to contaminate fabrics. The survival of
      these microorganisms was studied by testing the fabric swatches for microbial
      growth. RESULTS: The median survival times for all the tested bacteria and fungi
      were as follows: 26 days on cotton, 26.5 days on cotton-polyester, 28 days on
      silk, and 30 days on wool. Among the bacterial species tested, E. faecium had the
      longest survival time on cotton-polyester fabrics. For the fungal isolates, it
      was observed that C. tropicalis and C. krusei survived for the shortest amount of
      time on cotton fabrics in the present study. CONCLUSION: This survival data
      indicate that pathogenic microorganisms can survive from days to months on
      commonly used hospital fabrics. These findings indicate that current
      recommendations for the proper disinfection or sterilization of fabrics used in
      hospitals should be followed to minimize cross-contamination and prevent
      nosocomial infections.

PMID- 25610202
TI  - The Social and Health Problems of People Living with HIV/AIDS in Izmir, Turkey.
AB  - OBJECTIVE: The aim of this study was to describe how AIDS, as well as the stigma
      associated with it, affects the lives of HIV positive patients and their family
      members. MATERIALS AND METHODS: Three large state hospitals in the metropolitan
      area of Izmir participated in the study. Six focus groups were conducted with
      people infected with HIV (n=32) and their family members (n=11). Participants
      were asked to fill out a questionnaire to assess their HIV/AIDS knowledge and to
      convey how the stigma had affected them. RESULTS: The most important problems
      identified were society and work-related social problems and access to health
      services. The patients and their family members stated that education was needed
      to correct misconceptions about HIV and to help them cope with related problems.
      We found that patients and their family members were sensitive about disclosure.
      CONCLUSION: We determined the education, counseling and support needs of HIV
      infected patients and their families. Additionally, we found that health
      personnel who monitor the patients should make more efforts on patients'
      education and counselling.

PMID- 25610203
TI  - A Biomechanical Comparison between Salter Innominate Osteotomy and Pemberton
      Pericapsular Osteotomy.
AB  - OBJECTIVE: This study aims to compare the pelvic biomechanics of patients who
      underwent Salter innominate osteotomy (SIO) for one hip and Pemberton
      pericapsular osteotomy (PPO) for the other hip. MATERIALS AND METHODS: Fifty
      seven of 126 patients who received a one-stage procedure involving SIO for one
      hip and PPO for the other hip were included in this series. Preoperative x-rays,
      archived reports and patient recall were obtained and retrospectively analyzed
      for these 57 patients. Pelvic biomechanics of the two osteotomy techniques were
      compared on x-rays and computerized tomography imaging. RESULTS: Based on x-rays,
      three hips with SIO and 1 hip with PPO had changes that could reflect unstable
      pelvic biomechanics. SIO caused an average lower limb discrepancy of 0.47 cm in
      all patients. Positive results were found in 5 patients at their most recent
      clinical examination. CONCLUSION: PPO affects the biomechanics of the pelvis much
      less than SIO. PPO demonstrated ideal biomechanical results compared with SIO,
      with fewer changes to the pelvic ring and the hip joints.

PMID- 25610204
TI  - The Role of Alpha-2 Adrenergic Receptors in Anti-ulcer Activity.
AB  - Although peptic ulcer disease has long been recognized, the proposed mechanisms
      of its etiopathogenesis change every year. This review shows that gastric ulcers
      have a significant relationship with alpha-2 adrenergic receptors. The
      aggravating factors of gastric ulcer formation have been reported to act by
      blocking alpha-2 adrenergic receptors, whereas drugs possessing anti-ulcer
      activity have been shown to ensure gastric protection by stimulating the alpha-2
      adrenergic receptors. The data derived from the literature indicate the
      likelihood that any drug or substance selectively stimulating the alpha-2
      adrenergic receptors may possess anti-ulcer activity. 

PMID- 25610205
TI  - Juvenile alexander disease: a case report.
AB  - Alexander disease is a rare autosomal recessive disorder that is characterized by
      degeneration of the white matter in the central nervous system. Alexander disease
      is a leukodystrophy that is usually observed in early childhood but rarely in
      adults. It is characterized by megalencephaly, demyelinization and multiple
      Rosenthal fibers. Specific magnetic resonance imaging (MRI) findings and genetic
      investigations are necessary to diagnose the disorder. Signs of leukodystrophy
      were found in the bilateral white matter on a brain MRI of our four-year-old
      patient. He had megalencephaly since birth. We use this case to discuss Alexander
      disease. 

PMID- 25610206
TI  - Acquired reactive perforating collagenosis.
AB  - Acquired reactive perforating collagenosis (ARPC) is commonly recognized as an
      unusual skin reaction to superficial trauma that is observed in patients with a
      certain genetic predisposition or underlying diseases, such as diabetes mellitus
      or renal diseases. We present the unusual case of a 55-year-old female diabetic
      patient with numerous characteristic dome-shaped nodules, which consisted of
      central umbilication containing firm keratotic plugs. 

PMID- 25610207
TI  - Co-existence of tuberculous meningitis and pulmonary tuberculosis in a denim
      sandblaster.
AB  - Silicosis is a well-known occupational lung disease that was discovered by the
      ancient Greeks and Romans. In 2001, it has emerged again in an unexpected
      occupation: denim sandblasting. Exposure to crystalline silica, with or without
      clinical disease, is one of the most important predisposing factors for the
      development of tuberculosis; however, there has been no previous report of
      tuberculosis among cases of silicosis due to denim sandblasting. Herein, we
      report the first case of a denim sandblaster with silicosis who developed both
      pulmonary tuberculosis and tuberculous meningitis. 

PMID- 25610208
TI  - Recurrent atretic parietal cephalocele in adult and radiological findings.
AB  - Atretic parietal cephaloceles are an extremely rare and occult form of congenital
      herniations that involve the meninges, remnants of glial cells or central nervous
      system structures. They are detected as subscalp lesions that are covered by
      skin. In the literature, atretic parietal cephaloceles have been reported in
      children in 59 cases and in two cases in adults. We present here a case of a
      recurrent atretic parietal cephalocele that we recently observed in an adult.
      This case indicates that an atretic parietal cephalocele should always be
      considered in the differential diagnosis of subscalp lesions. Radiologic
      diagnosis is a lifesaving measure that can be undertaken before an operation.
      Additionally, regular follow-up magnetic resonance imaging is recommended for
      each case with remnant lesions due to the slow growth of these masses. 

PMID- 25610209
TI  - Intracranial cystic metastases from breast cancer.

PMID- 25610210
TI  - MRCP Imaging of Intraductal Papillary-Mucinous Neoplasm of the Pancreas.

PMID- 25610211
TI  - Wound healing and mucosal immunity during short Mars analog environment mission:
      salivary biomarkers and its clinical implications.
AB  - OBJECTIVE: Wound healing in an extreme environment with micro-gravity is not well
      characterized, despite the likelihood that the increasing use of manned
      spaceflight as a research and commercial enterprise raises the probability of
      traumatic injury in this state. Hence, this study was conducted to determine the
      impact of the isolated environment of the Mars Desert Research Station on mucosal
      immunity and wound healing. MATERIALS AND METHODS: Two punch biopsy wounds were
      placed on the hard palate of two crewmembers. The first wound was made during
      summer vacation, whereas the second was placed on the contra-lateral side 3 days
      before the Mars analog mission began. Thus, each crewmember served as his/her own
      control. Two independent methods were used to assess healing. A ten-item
      perceived stress scale, salivary cortisol, Immunoglobulin A, IgG and IgM were
      measured. RESULTS: There were significant differences in the proportion of the
      wound size healed between vacation and the mission. Salivary IgA, IgM, IgG and
      cortisol levels showed significant differences between vacation and mission.
      CONCLUSION: These data suggest that stress can have significant consequences for
      wound healing. The effects of stress on wound repair could have important
      clinical implications, including for recovery from surgery.

PMID- 25610212
TI  - The influence of reduction mammaplasty on dermato-psychiatric disorders.
AB  - OBJECTIVE: Macromastia can cause psychiatric disorders, such as anxiety and
      depression, and decreases in self-esteem and self-confidence. These problems
      often externalize themselves on the skin, causing lesions characterized by
      various degrees of excoriations and lichenified plaques. Mammaplasty operations
      are very effective in the treatment of neurotic excoriations and similar skin
      lesions as well as any underlying psychiatric disorders. MATERIALS AND METHODS:
      This study included 17 patients with macromastia and neurotic excoriation lesions
      who underwent psychiatric treatment for various reasons. Follow ups were
      performed using routine photographs used in breast surgeries. RESULTS: During the
      postoperative follow ups, the excoriations for nearly every patient healed within
      2 weeks. Some lesions healed with atrophic scars and some with permanent
      hyperpigmentation. Patients' physical complaints, such as backache, shoulder ache
      and submammary pruritic dermatitis, were also observed to heal. In addition, the
      patients stated that they felt better psychologically, and most also reported
      stopping psychiatric treatment. CONCLUSION: The psychological problems caused by
      macromastia include neurotic excoriation and similar skin problems, and aesthetic
      reduction mammaplasty surgeries are very effective in the treatment of these
      lesions. Body image perception comprises an important part of self-respect and
      self-esteem, and psychological-status cosmetic surgery can be evaluated as an
      alternative to psychological treatment.

PMID- 25610213
TI  - Magnetic resonance arthrography of the glenohumeral joint: ultrasonography-guided
      technique using a posterior approach.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy and feasibility
      of ultrasound (US)-guided magnetic resonance (MR) arthrography of the
      glenohumeral joint via a posterior approach. MATERIALS AND METHODS: Thirty-four
      patients (18 males and 16 females) who were suspected to have glenohumeral joint
      pathology were examined using MR arthrography. The patients ranged in age from 21
      to 85 years, and the average age was 45+/-15.9 years. A Toshiba Xario US unit was
      utilized. Ultrasonography examinations were conducted using a broad-band 5-12 MHz
      linear array transducer. Gadolinium was injected into the shoulder joint using an
      18-20 gauge needle. MR imaging was performed within the first 30 min after the
      injection. RESULTS: The injection of gadolinium into the shoulder joint was
      successfully accomplished in all 34 patients. Major contrast media extravasation
      outside the joint was depicted in only two patients (5.9%). No major
      complications were encountered. CONCLUSION: Ultrasonography is an effective
      alternate guidance technique for the injection of gadolinium into the
      glenohumeral joint for MR arthrography. US-guided arthrography via a posterior
      approach to the glenohumeral joint is safe, accurate, well tolerated by patients
      and easy to perform with minimal training.

PMID- 25610214
TI  - Surgical treatment of pulmonary hydatid cysts, which perforated to the pleura.
AB  - OBJECTIVE: Hydatid cyst disease, endemic in Eastern region of Turkey, is a
      significant parasitic public health problem. In this study, pleural complications
      of hydatid cysts were presented in 76 cases. MATERIALS AND METHODS: In our study,
      of the 412 pulmonary hydatid cyst cases operated on between 2003 and 2011, 76
      cases had ruptured into the pleura for various reasons, and the different
      clinicoradiological presentations were evaluated retrospectively. The age
      distribution of the cases was between 7 and 56 years, and the mean age was
      26.20+/-13.04. RESULTS: The most frequent symptom due to pleural rupture in
      patients was dyspnea (44 cases, 57.8%). Etiologically, iatrogenic perforation was
      detected in four cases and thoracic trauma in nine cases (six car accidents and
      three falls from a height). An anthelmintic drug use history was found in three
      cases of ruptured pleura. Spontaneous perforation was detected in the other 60
      (78.9%) cases. Two cases that were admitted to the emergency unit and were
      immediately administered a tube thoracostomy developed tension pneumothorax. In
      addition, 21 cases had hydropneumothorax, 17 had pneumothorax, and 36 had
      pleurisy. Morbidity was observed in 30 cases (39.4%). Atelectasis was the most
      frequent cause of morbidity in these patients (10 cases). The mean duration of
      hospitalization was determined to be 12.26+/-2.90 days. CONCLUSION: This disease
      can progress asymptomatically for a long time and can sometimes lead to life
      threatening emergency situations, such as tension pneumothorax. The delayed
      admission of a patient to a physician causes the disease to become more
      complicated and to increase the morbidity and mortality rates. Treatment of the
      disease is in the form of surgery. Possible parenchymal protection should be
      applied in surgical treatment, and anatomic resection should not be performed
      unless necessary.

PMID- 25610215
TI  - Cost-effectivity analysis of one-step versus two-step screening for gestational
      diabetes.
AB  - OBJECTIVE: Early diagnosis of gestational diabetes mellitus (GDM) is important
      for both maternal and fetal health. The literature has varying recommendations
      about one-step and two-step tests for GDM screening and diagnosis. The present
      study aimed to investigate the difference in the cost and duration of hospital
      stay of a one-step procedure compared to a two-step procedure, which is routinely
      performed in our hospital. MATERIALS AND METHODS: The two-step procedure was
      performed in 2,724 pregnant women, and the one-step procedure was performed in
      185 pregnant women. The one-step and two-step screening procedures for
      gestational diabetes were compared with respect to the duration of hospital stay
      and cost. RESULTS: The test cost per woman was 0.75 TL less in the one-step
      procedure; however, the duration of the one-step test was 18.6 min longer, and
      the number of blood sampling procedures was 1.08 times higher. CONCLUSION: The
      one-step method may be preferred over the two-step (or glucose challenge) test
      due to its diagnostic value and lower cost.

PMID- 25610216
TI  - Sociodemographic characteristics, clinical signs and quality of life in patients
      with fibromyalgia.
AB  - OBJECTIVE: We aimed to evaluate the sociodemographic and clinical characteristics
      as well as the quality of life of patients with fibromyalgia (FM). MATERIALS AND
      METHODS: A total of 37 female patients diagnosed with FM and 31 healthy females
      were included into the study. Individuals were asked about their demographic
      characteristics. The number of sensitive points (NSP), skin fold sensitivity,
      cutaneous hyperemia and reticular skin changes of patients and healthy controls
      were evaluated during physical examination. Individuals were evaluated for pain
      severity using the Visual Analogue Scale (VAS), for psychological states using
      the Beck Depression Scale (BDS), for quality of life using the Short Form-36 (SF
      36) and for functional status using the Fibromyalgia Impact Questionnaire (FIQ).
      RESULTS: The mean age of FM patients was 39.2+/-6.5 years versus 39.1+/-6.2 years
      in the controls. The most frequently encountered FM symptoms were fatigue
      (94.6%), sleep disturbances (86.5%) and anxiety (86.5%). Differences between FM
      patients and controls were statistically significant for NSP (p=0.001), VAS
      (p=0.001), FIQ (p=0.001), BDS (p=0.001) and SF-36 (p=0.003), and FIQ subgroups
      were also different between the two groups (p<0.001). In the SF-36 survey, FM
      patients were different from the control in the physical function (p=0.001), pain
      (p=0.005), general health (p=0.017), physical fitness (p=0.003), and mental
      health (p=0.008) portions of the survey. CONCLUSION: Fibromyalgia has distinct
      clinical features that lead to low functional capacity and quality of life. Thus,
      patients' sociodemographic characteristics and the evaluation of their quality of
      life may be important in the diagnosis and monitoring of treatment progress.

PMID- 25610217
TI  - Obesity and its diagnostic methods in Turkish children.
AB  - OBJECTIVE: The application of body mass index (BMI) for obesity classification in
      all population studies has been questioned by the scientific community. It has
      been found that the bioelectrical impedance analysis (BIA) is an accurate method
      for screening obesity. This study was conducted to evaluate the accuracies of
      BMI, skinfold thickness (SFT), leptin and BIA measurements in obesity
      classification and to find correlations between BIA and the other indicators for
      obesity. MATERIALS AND METHODS: This case-control study included 178 children of
      whom 90 were in the obese group and 88 in the control group. The study measured
      BMI, SFT, leptin level and BIA-mediated body fat percentage (BIA BFP) in each
      child. RESULTS: The BMIs, leptin levels, SFTs and BIA BFPs of children in the
      obese group were found to be higher than those in the control group (p<0.001).
      The measurement of BIA BFP strongly correlated with BMI, SFT and waist
      circumference, whereas BIA BFP measurement showed weak-moderate correlation with
      leptin level. CONCLUSION: Bioelectrical impedance analysis was found to be an
      accurate measure of BFP in obesity. In addition, BIA may prevent the incorrect
      diagnosis of obesity as determined by BMI alone, especially in boys during the
      pubertal period.

PMID- 25610218
TI  - Comparison of esmolol to nitroglycerine in controlling hypotension during nasal
      surgery.
AB  - OBJECTIVE: The aim of this study was to compare esmolol to nitroglycerine in
      terms of effectiveness in controlling hypotension during nasal surgery. MATERIALS
      AND METHODS: After approval by our institutional Ethics Committee, 40 patients
      were recruited and randomized into two drug groups: esmolol (Group E) and
      nitroglycerine (Group N). In group E, a bolus dose of 500 MUg/kg esmolol was
      administered over 30 sec followed by continuous administration at a dose of 25
      300 MUg/ kg/min to maintain systolic arterial pressure at 80 mmHg. In group N,
      nitroglycerine was administered at a dose of 0.5-2 MUg/kg/min. RESULTS: During
      the hypotensive period, systolic arterial pressure, diastolic arterial pressure,
      mean arterial pressure, and heart rate were decreased 24%, 33%, 27% and 35%,
      respectively, in group E (p<0.001, p<0.001, p<0.001, p<0.001) and were decreased
      30%, 33%, 34% and 23%, respectively, in group N (p<0.001, p<0.001, p<0.001,
      p<0.001). The decrease in heart rate was higher in group E during the hypotensive
      period (p=0.048). During the recovery period, diastolic arterial pressure and
      heart rate were decreased 9% and 18%, respectively, in group E (p=0.044,
      p<0.001). Systolic arterial pressure, diastolic arterial pressure, and mean
      arterial pressure were decreased 7%, 3% and 7%, respectively, in group N
      (p=0.049, p=0.451, p=0.045). CONCLUSION: Esmolol provides hemodynamic stability
      and good surgical field visibility and should be considered as an alternative to
      nitroglycerine.

PMID- 25610219
TI  - Diagnostic magnetic resonance imaging of the breast.
AB  - Contrast enhanced breast magnetic resonance imaging is a modality that is
      frequently used into the breast radiologist's daily clinical practice. MRI
      examination should have optimal technical proficiency in order to attain
      diagnostic quality avoiding false positive and negative diagnoses. Furthermore,
      due to increasing usage fields of the examinations uniting with high sensitivity
      phenomenon, excessive usage and excision/interventional procedures are
      inevitable. Therefore, we hope to highlight the appropriate usage of the MRI
      technique and it's clinical applications. 

PMID- 25610220
TI  - Cecal volvulus: a rare cause of intestinal obstruction.
AB  - Cecal volvulus is a rare cause of intestinal obstruction. In this report, we
      present a 41 year-old patient with cecal volvulus, and we discuss this very rare
      entity. 

PMID- 25610221
TI  - Escobar syndrome mimicing congenital patellar syndrome.
AB  - Multiple pterygium syndrome (MPS) is a syndrome that is characterized abnormal
      face, short length and skin pterygiums on some body legions (servical,
      antecubital, popliteal, interdigital and on neck). It is also called as Pterygium
      Colli syndrome, Escobar syndrome or Pterygium syndrome. Escobar (multyple
      pterygium) syndrome is a rare syndrome. Intrauterin growth reterdation, abnormal
      face, wide-spead pterygiums that resulted in joint contractures, ptosis,
      chryptoorchidism, patellar dysplasia and foot deformities are seen on this
      syndrome. Primarly autosomal resesive crossing are observed; also autosomal
      dominant and X-linked crossing. This case were presented as it has components of
      Escobar syndrome and Isolated Patellar Aplasia syndrome in same time. 

PMID- 25610222
TI  - The occurrence of priapism as a result of the use of a single dose of quetiapine.
AB  - Priapism is a prolonged pathologic erection situation that occurs after sexual
      stimulation or without sexual stimulation. This condition is divided into two
      types, ischemic (low-flow, veno-occlusive) and non-ischemic (high-flow,
      arterial). A 68-year-old male patient applied to our clinic with the complaints
      of hardness and pain in the penis. Three days before he applied to our clinic, he
      was prescribed a single dose of 200 mg quetiapine by a psychiatry polyclinic for
      the complication of insomnia. Nearly 6 hours after the first dose of quetiapine,
      an involuntary erection occurred with accompanying pain in the penis. The patient
      waited for spontaneous detumescence without consulting a psychiatrist. After the
      patient had waited for 48 hours without any change, he applied to our clinic.
      Other etiologic factors of priapism were excluded (such as malignancy, blood
      dyscrasia, leukemia, and trauma). In blood gas samples obtained from the corpus
      cavernosum, hypoxia, hypercarbia, and acidosis were diagnosed. Ischemic priapism
      was supposed. We conclude that priapism can be viewed as a new possible side
      effect of quetiapine and that patients should be warned about this side effect. 

PMID- 25610223
TI  - The importance of flowmetry in carotid body tumor surgery: a case report.
AB  - Carotid body tumors arise from the embryonic neural crest. These tumors are
      mostly benign, and they rarely show character. Bifurcation of the carotid body
      cells originates from a common carotid paraganglion; a tumoral mass lateral to
      the carotid bifurcation is usually found in the neck. A pathologic feature of
      these tumors is that they have a tendency to wrap because they are not treated
      with the external and internal carotid arteries. In our clinic, we operated on a
      patient who had been diagnosed with carotid body tumor. After removal of the
      internal carotid artery, the mass flow due to a decrease in the light of
      literature used to evaluate the importance of flowmetry carotid surgery. 

PMID- 25610224
TI  - Hepatic Alveolar Echinococcosis that Incidentally Diagnosed and Treated with R1
      Resection.
AB  - In this report, we present an incidentally diagnosed and surgically treated
      patient with hepatic alveolar echinococcosis. 

PMID- 25610225
TI  - Catheterization of the Lumbar Artery via the Superior Mesenteric Artery During
      Type 2 Endoleak Treatment.

PMID- 25610226
TI  - Anti-cyclic citrullinated Peptide frequency in patients with chronic hepatitis C
      virus infection and effect of presence of systemic disease.
AB  - OBJECTIVE: Patients with chronic hepatitis C virus (HCV) infection may show a
      variety of rheumatic symptoms and signs. Anti-cyclic citrullinated peptide (anti
      CCP) is widely used as as a marker, particularly for rheumatoid arthritis (RA),
      and may be positive in some diseases that also cause arthritis, such as systemic
      lupus erythematosus, familial Mediterranean fever, Behcet's disease, and
      psoriatic arthritis. MATERIALS AND METHODS: Blood samples were obtained (in
      routine protocols) from 57 patients with chronic HCV infection from the
      Gastroenterology Clinic of Ataturk University and Infectious Disease Clinic of
      Erzurum Region Research and Education Hospital. Normal sera were obtained from
      volunteer blood donors at Ataturk University. RESULTS: Anti-CCP antibodies were
      found in 5 chronic HCV patients with RA. The patient with the highest anti-CCP
      antibody level had RA. No patient in the control group was positive for anti-CCP
      antibodies. CONCLUSION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies
      should be measured frequently in patients with HCV and an additional systemic
      disease, such as end-stage chronic renal failure, chronic obstructive airway
      disease, and decompensated liver cirrhosis, to differentiate RA from non-RA
      arthropathy.

PMID- 25610227
TI  - Anatomical preconditions for operative-technical errors in right
      trisectionectomy.
AB  - OBJECTIVE: Certain anatomical variations may represent preconditions for
      technical operation errors in right trisectionectomy. These variations include:
      the confluence of the common bile duct, the length of the left hepatic duct, the
      localization of the bile duct confluence for segments 2 and 3 of the umbilical
      portion of the left portal vein and the peculiarities of the afferent and
      efferent blood supply of these two segments. The aim of the present study is to
      identify and discuss such preconditions. MATERIALS AND METHODS: The anatomical
      variations of the common bile duct confluence were analyzed by intraoperative
      cholangiography in 112 patients undergoing liver resections and in 32
      preparations after left hepatectomy. The variations of the afferent and efferent
      blood supply were morphologically examined in 43 liver resections. RESULTS: Seven
      types of anatomical variations of the common bile duct confluence were detected
      through intraoperative cholangiography, and three were extracted from the
      available literature. Three anatomical types (central, peripheral, and combined)
      of bile drainage from segment 4 were established. The mean distance between the
      bile duct confluence for segments 2 and 3 and the main hepatic duct confluence,
      i. e., the length of the left hepatic duct, was 3.68 cm. The anatomical
      peculiarities of the afferent and efferent arterial and venous supply of segments
      2 and 3 were presented and discussed with respect to their roles in a safe right
      trisectionectomy. CONCLUSION: Surgeons' sound knowledge of anatomical variations
      of the biliary tract and hepatic blood vessels coupled with increased experience
      and technique refinements could contribute to better outcomes in right
      trisectionectomy.

PMID- 25610228
TI  - Maxillofacial fracture experiences: a review of 152 cases.
AB  - OBJECTIVE: The fractures of facial structures lead to great morbidity. Cross
      sectional studies are needed to evaluate the current state of maxillofacial
      traumas. Thus, this study aims to evaluate these experiences and to compare these
      results with the current literature. MATERIALS AND METHODS: The medical records
      of the maxillofacial fracture cases hospitalized between January 2004 and
      November 2011 were examined. The age, sex, etiology, fracture localization and
      treatment method for each case were documented. The affected facial bones were
      grouped as mandible, maxilla, zygoma, naso-orbitoethmoid complex (NOEC) and blow
      out. Nasal fractures were excluded. The cases were assigned to 3 groups with
      respect to age (below 16, above 65 and between 17 and 64). The chi Square test
      was used to assess the significance of the difference in mandibular fracture
      rates in the pediatric population compared to others. RESULTS: The total number
      of cases was 152. The total number of fractures was 185. Of the 152 cases, 117
      were male and 35 were female. The average age was 31.4 (+/-18.3), ranging between
      2 and 81. Thirty-one cases were 16 years old or less. Nine cases were 65 years
      old or more. Mandibular and zygomatic fractures were the most prevalent fractures
      in the adult group. Mandibular fractures were significantly more common in the
      pediatric age group compared to rest of the population (X(2), p<0.05). Traffic
      accidents were the most common etiological factor, with a 55.3% ratio. Open
      reduction and internal fixation was the most frequently conducted treatment
      modality in all age groups. CONCLUSION: Retrospective studies are important for
      the projection of future prospects. In summary, our results indicate that
      pediatric fractures are mostly in the lower face and usually affect the condylar
      region, which is consistent with the literature.

PMID- 25610229
TI  - Helicobacter pylori infections in chronic obstructive pulmonary disease.
AB  - OBJECTIVE: We aimed to investigate the prevalence of Helicobacter pylori (H.
      pylori) in patients with chronic obstructive pulmonary disease (COPD) using the C
      14 urea-breath test (C14UBT) and to determine whether there is an association
      between H. pylori infection and the severity of COPD. This is the first report in
      the literature of the use of C14UBT to investigate the prevalence of H. pylori in
      patients with COPD. MATERIALS AND METHODS: Fifty subjects with COPD (38 males and
      12 females, aged 61+/-10 years) and 20 control subjects (10 males and 10 females,
      aged 55+/-11 years) were evaluated. C14UBT was used to determine H. pylori
      infection. RESULTS: The prevalences of H. pylori infection in subjects with COPD
      and in controls were 72% and 65%, respectively (p=0.56). Forced expiratory volume
      in one second (FEV1) and forced vital capacity (FVC) values were significantly
      higher in the H. pylori-infected subjects with COPD than in the uninfected
      subjects (p=0.008 and p=0.006, respectively). CONCLUSION: The presence of H.
      pylori infection in COPD patients affects pulmonary functions, but the effects of
      H. pylori infection on the respiratory system and COPD are not clear.

PMID- 25610230
TI  - The Prevalence of Chronic Impingement Syndrome and SLAP Lesion and the
      Sensitivity of O'Brien's Test.
AB  - OBJECTIVE: In this study, we aimed to investigate the prevalence of SLAP lesions
      in patients with chronic impingement syndrome. We also examined the sensitivity
      of O'Brien's test. MATERIALS AND METHODS: The study included 48 patients with a
      preliminary chronic impingement syndrome diagnosis to whom arthroscopic
      decompression had been planned. All patients underwent preoperative Neer's,
      Hawkins' and O'Brien's tests. We performed shoulder arthroscopy on all patients
      and evaluated chronic impingement syndrome and SLAP lesions. Then, we compared
      the statistical sensitivities of these tests. RESULTS: The mean age of patients
      with chronic impingement was 45.8 years (range, 35-69 years). O'brien's test was
      positive in 34 (70.8%) of the patients, and Neer's test and Hawkins' test were
      positive in 46 (95.8%) of the patients before shoulder arthroscopy. Shoulder
      arthroscopy revealed that 44 (91.7%) of 48 patients had subacromial impingement;
      32 (66.7%) had SLAP lesions and internal impingement. In chronic impingement
      syndrome, sensitivity rates were 95.6% for Neer's test and Hawkins' test, whereas
      in internal impingement syndrome and slap lesions, the sensitivity of O'brien's
      test was 94.1%. There was no statistical difference between the tests (p>0.05).
      CONCLUSION: 72.72% of the patients with chronic impingement syndrome had
      concomitant SLAP lesions. We suggest that O'Brien's test should be used with
      Neer's and Hawkins' tests for diagnosis of this condition.

PMID- 25610231
TI  - Relationship of serum paraoxonase enzyme activity and thermal burn injury.
AB  - OBJECTIVE: This study investigated changes in serum oxidative stress parameters
      in burn cases compared to healthy controls. MATERIALS AND METHODS: This study was
      performed in 41 burn patients with mild to severe thermal burn injuries and 38
      healthy volunteers. The burn cases were selected from patients who were
      hospitalized in the burn unit for the treatment of second- and third-degree
      burns. Malondialdehyde (MDA) levels and PON-1 paraoxonase and arylesterase
      activities were measured in patient serum samples. RESULTS: PON-1 paraoxonase
      activity and MDA levels in patients with major thermal burn injury were
      significantly higher than healthy controls, but PON-1 arylesterase activities
      were lower. A significant negative correlation was observed between the burn
      percentage of the total body surface area and the PON-1 arylesterase activities
      in patients. CONCLUSION: Human thermal burn injury was associated with an
      increase in MDA production and a decrease in PON-1 arylesterase activity, which
      was proportional to the percentage of total burned surface area.

PMID- 25610232
TI  - Comparison of Open Bankart Repair versus Modified Bristow Operation for the
      Treatment of Traumatic Recurrent Anterior Dislocation and Capsular Laxity of the
      Shoulder.
AB  - OBJECTIVE: The purpose of this study was to compare the results of open Bankart
      repair versus those of modified Bristow operation in patients with recurrent
      anterior dislocations of the shoulder, the last of which was caused by a minor
      trauma. MATERIALS AND METHODS: This study included 38 patients (34 (89.5%) male
      and 4 (10.5%) female) who presented recurrent dislocation of the shoulders with
      capsular laxity and who underwent an open Bankart repair or a modified Bristow
      operation. The mean age of the patients was 29.6 years (range, 17-60 years). The
      mean follow-up period was 5.5 years (range, 35 months to 9 years). A total of 25
      patients (65.8%) underwent an open Bankart repair, whereas 13 (34.2%) underwent a
      modified Bristow operation. The treatment results were assessed using the Rowe
      score for instability. RESULTS: Of the 38 shoulders assessed, 24 (63.1%) were
      right shoulders and 14 (36.9%) were left shoulders. Furthermore, 26 (68.4%) were
      the dominant shoulders of the patients, and 12 (31.6%) were the non-dominant
      shoulders. The mean time from the first dislocation was 3.8 years (range, 10
      months to 11 years). The age at which the first shoulder dislocation occurred was
      20 years or younger in 7 cases (18.4%), 21-30 years in 22 cases (57.9%), 31-40
      years in 6 cases (15.8%) and 41 or older in 3 cases (7.9%). The patients had
      experienced 4-10 recurrent dislocations in 15 cases (39.5%), 10-20 recurrent
      dislocations in 10 cases (26.3%) and 20 or more recurrent dislocations in 13
      cases (34.2%). The mean Rowe score was 85.6 following open Bankart repair and
      81.9 following modified Bristow. No significant difference was observed between
      these good and excellent Rowe scores following the open Bankart repair and the
      modified Bristow operation (p>0.05). CONCLUSION: Proper patient selection for the
      open Bankart repair and the modified Bristow operation is crucial. When the
      proper patients have been selected for these procedures, both produce
      satisfactory results for the treatment of patients with capsular laxities.

PMID- 25610233
TI  - Diagnosis of Peritoneal Metastases with Abdominal Malignancies: Role of ADC
      Measurement on Diffusion Weighted MRI.
AB  - OBJECTIVE: The purpose of our study was to evaluate the utility of the apparent
      diffusion coefficient (ADC) value measurement in the diagnosis of peritoneal
      metastases on diffusion weighted magnetic resonance imaging. MATERIALS AND
      METHODS: Diffusion weighted imaging with conventional magnetic resonance imaging
      sequences was performed on twenty consecutive oncology patients (group I) with
      peritoneal metastases. The ADC values of the metastases, the peritoneal fat
      around the metastases (group I) and the peritoneal fat in patients with no
      malignancy (group II) at b(0-100), b(0-600), and (b 0-1000) s/mm(2) gradients
      were measured and compared. RESULTS: The apparent diffusion coefficient values of
      three gradients in peritoneal metastases (2.27+/-0.4; 1.67+/-0.7 and 1.09+/
      0.4*10(-3) mm(2)/s at b 100, 600 and 1000 gradients, respectively) were
      significantly lower than the ADC values of the peritoneal fat around metastases
      (3.07+/-0.4; 2.07+/-0.4; 1.33+/-0.3*10(-3) mm(2)/s at b 100, 600 and 1000
      gradients, respectively) (p<0.05). There was no significant difference between
      the ADC values of peritoneal fat in the patients of group I and group II at the 3
      diffusion gradients (p>0.05). CONCLUSION: The measurement of ADC values may be
      used as a complementary diagnostic method in differentiating peritoneal
      metastases from peritoneal fat on Diffusion Weighted MRI (DWMRI DWMRI).

PMID- 25610234
TI  - Is red cell distribution width a marker for the presence and poor prognosis of
      cardiovascular disease?
AB  - Red cell distribution width (RDW) is an indices heterogeneity of cell size in the
      peripheral blood and has been shown to be an independent correlate of adverse
      outcomes in healthy subjects and in some cardiac conditions. Additionally, RDW is
      associated with both the presence and the complexity of vascular disease. In this
      review we investigate the importance of RDW in vascular disease in the light of
      recent information. 

PMID- 25610235
TI  - Female Adnexial Tumor of Probable Wolffian Origin (FATWO) without Ki-67
      Expression Reflecting Low Malignant Potential in a 55-Year-Old Woman.
AB  - Female adnexial tumors of probable Wolffian origin (FATWO) are rare tumors
      derived from the remnants of the mesonephric duct. These tumors generally exhibit
      a low malignant potential, but recurrence and or metastasis is possible during
      the course of the disease according to the tumors' possible malignant potential.
      We report a case of FATWO without estrogen and progesterone receptors and with
      negative immunostaining for Ki-67 (a proliferation marker) as a probable low
      malignant-potential tumor. A 55-year-old woman presented with a complaint of
      heavy menstrual bleeding and pelvic pain. Pre-operative ultrasonographic
      evaluation revealed an intramural uterine leiomyoma of 4 cm in diameter and a
      right adnexial solid mass measuring 5 cm in diameter. Following total abdominal
      hysterectomy and bilateral salpingo-oophorectomy, immunostaining based on the
      labeled streptavidin-biotin method was performed on sections from representative
      blocks of paraffin-embedded tissues sampled from the mass, revealing a low
      mitotic index with negative Ki-67 immunostaining. Immunohistochemical staining
      with promising new markers and pathological investigation of the entire tumor are
      needed to determine the malignant behavior of an individual FATWO. Ki-67 is a
      helpful marker for determining Wolffian duct tumors' potential malignant
      behavior. 

PMID- 25610236
TI  - A rare thymoma type presenting as a giant intrathoracic tumor: lipofibroadenoma.
AB  - Type B1 thymoma (lipofibroadenoma) is extremely rare. The tumor is characterized
      by an organoid appearance rich in lymphocytes with medullary differentiation and
      perivascular spaces. A twenty-three-year-old female patient was admitted to our
      clinic with complaints of chest pain and dyspnea for six months. Chest computed
      tomography showed solid and fatty components of masses 21*7 and 5*7 cm with clear
      borders in the right thoracic cavity. The patient underwent a posterolateral
      thoracotomy in which the mass, arising from the anterior mediastinum, was
      resected. Histopathological examination showed that the mass was Type B1 thymoma,
      and the patient was presented in light of the literature. 

PMID- 25610237
TI  - Wide central pontine, bulbar and thalamic myelinolysis with sequela.
AB  - Although cases of hyponatremia during pregnancy have been described, it has
      rarely been possible to show demyelination lesions in central pons, bulbus as
      well as thalamus, by imaging techniques. We report a case that developed
      extensive myelinolysis due to the "rapid" correction of hyponatremia as a result
      of hyperemesis gravidarum. Magnetic resonance imaging showed bilaterally
      symmetric hyper-intense areas in the thalamus and cerebral crus and symmetric
      hyperintense area in the central pons, with sparing of the rim. In the second day
      of hospitalization, probably as a result of expansion of myelinolysis, she was
      intubated and received mechanical ventilator due to bradypnea and a GCS scale of
      E1M4V2. She was extubated in 11(th) day of hospitalization and physical therapy
      was started. She was discharged in 30(th) day of hospitalization with a GCS of
      15. But she was tetraparetic (2/5). In the 3(rd) month of follow up, her
      quadriparesis improved to paraparesis in lower extremities (3/5). Her follow up
      examinations in the first year did not change although physical therapies go on.
      She delivered a normal child. 

PMID- 25610238
TI  - Gastric foregut duplication cyst as a rare cause of abdominal pain.
AB  - Gastric foregut cyst is a rare congenital disease. In this report, a gastric
      foregut cyst in a 22-year-old male patient is presented. Fluid-filled gastric
      ultrasonography and computed tomography demonstrated a cystic, calcified lesion
      attached to the anterior gastric wall. The same lesion was observed using upper
      gastrointestinal endoscopy. An exploratory laparotomy revealed a non
      communicating cyst. The cyst was excised surgically, and pathology confirmed the
      diagnosis. 

PMID- 25610239
TI  - Complete nasopharyngeal stenosis: presentation of a rare case.
AB  - A sixty-eight years old female patient with complete nasopharyngeal stenosis
      without any determined etiology is presented. She had complete nasal obstruction
      as well as obstructive sleep apnea syndrome. She was operated and dense, thick,
      avascular fibrotic tissues were excised and reconstructed with local flaps and
      skin graft. Only partial opening was achieved in the long term follow-up. 

PMID- 25610240
TI  - MDCT Diagnosis of Infracardiac Total Anomalous Pulmonary Venous Return.

PMID- 25610241
TI  - Dose-dependent protective effect of L-carnitine on oxidative stress in the livers
      of hyperthyroid rats.
AB  - OBJECTIVE: The present study was designed to investigate the dose-dependent
      protective effect of L-carnitine (LC) on thyroid hormone-induced oxidative stress
      in rat liver tissue. MATERIALS AND METHODS: Twenty-one male Sprague Dawley rats
      were divided into four groups: control, hyperthyroidism, hyperthyroidism plus L
      carnitine 100, and hyperthyroidism plus L-carnitine 500. Hyperthyroidism was
      induced in rats by injecting 250 MUg of L-thyroxine/kg body weight/day for twenty
      consecutive days. The activities of catalase (CAT), glutathione peroxidase (GPX)
      and myeloperoxidase (MPO) and the level of malondialdehyde (MDA) were measured in
      liver homogenates. RESULTS: The liver CAT, GPX and MPO activities were
      significantly lower in the hyperthyroid rats than in the control group. Treating
      hyperthyroid rats with both low-dose (100 mg/kg) and high-dose (500 mg/kg) L
      carnitine for 10 days resulted in a marked increase in the activities of the
      antioxidant enzymes in the liver tissue. CONCLUSION: The present study indicates
      that the low-dose L-carnitine application was sufficient to prevent L-thyroxine
      induced oxidative stress in rat livers.

PMID- 25610242
TI  - Surgical Measurement of the Sphenoid Sinus on Sagittal Reformatted CT in the
      Turkish Population.
AB  - OBJECTIVE: The objectives of this study were to determine sinus measurements
      specific for the Turkish population using CT sagittal thin-slice reconstruction
      images and to clarify the three-dimensional anatomical features of the sphenoid
      sinus, along with its surrounding structures, that are relevant to performing an
      endoscopic sphenoidotomy. MATERIALS AND METHODS: Images of 300 patients (165
      female, 135 male) were studied. The research was conducted on the axial plane
      with a 1 mm slice thickness and a 0.6 mm slice interval, and sagittal
      reconstruction was performed with a 0.4 mm slice interval. Measurements of the
      sinus were obtained, and the presence of Onodi cells was researched. RESULTS:
      Line 1 was found to be significantly shorter in the Turkish patients of this
      study compared to studies of other populations. Lines 4 and 6 were found to be
      longer on the left side (Line 4 right: 18.8+/-3.6 mm, left: 19.3+/-3.4 mm,
      p=0.027; Line 6 right: 24.1+/-6.8 mm, left: 24.3+/-6.8 mm, p=0.008). Lines 2, 3,
      4 and 6 were longer in men than in women (p<0.05). CONCLUSION: In the Turkish
      population, Line 1 is shorter, so the risk of skull base perforation is greater.
      Lines 4 and 6 are longer on the left side; thus, choosing the left ostium in
      sinus dilation is safer. Because of sex differences regarding Lines 2, 3, 4 and
      6, sex should be considered in sphenoid sinus procedures.

PMID- 25610243
TI  - The prevalence and risk factors of human papillomavirus in female sex workers.
AB  - OBJECTIVE: Human papillomavirus virus (HPV) is the major causative factor for
      cervical cancer, and sex workers are at high risk for HPV infection. In this
      study, we aimed to estimate the prevalence and risk factors of HPV infection
      among female sex workers (FSWs). MATERIALS AND METHODS: The study included 239
      brothel-based FSWs who work in Izmir, Turkey. A self-administered questionnaire
      for risk factors was completed, and cervical brush samples were taken for HPV
      detection and typing. HPV detection and typing were performed by multiplex
      polymerase chain reaction (PCR) and reverse hybridization methods. The risk
      factors related to HPV infection were determined by multivariate analysis.
      RESULTS: The prevalence of HPV among FSWs was 20.1%. HPV18 was the most common
      type (40%), followed by HPV16 (17%) and HPV50 (15%). Logistic regression analysis
      revealed that being less than 30 years of age, having a high frequency of sexual
      contacts, smoking, and lack of condom use were significantly associated with HPV
      infection. CONCLUSION: FSWs have a high prevalence of HPV infection and are at
      increased risk for cervical cancer. As they are a priority group for active
      follow-up, national strategies for reducing HPV among FSWs and regular cervical
      cancer screening programs should be implemented for this population.

PMID- 25610244
TI  - Analysis and Toxicity of Plain (PMP) and Blended (PMT) Indian Pan Masala (PM).
AB  - OBJECTIVE: Betel leaf combined with areca nut is known as betel quid pan masala
      (PM), and tobacco with areca nut, catechu and lime is pan masala (PMT) blended
      with gulkhand. These narcotics are popular among young and old individuals. A
      prima facia chemical analysis and a toxicity assessment of PM in mice were
      conducted to study the relationship between longtime consumption of PM and health
      hazards. MATERIALS AND METHODS: Chemical analysis of different types of PM was
      done employing HPLC, GLC, AAS, ES, TLC, GCMS and sequential extraction for PAH,
      pesticides, metals and minerals, electrolytes, drugs and xenobiotics. Ethanolic
      PM extracts were tested by IP and PO routes in inbred Swiss mice. RESULTS: PAH,
      which are known xenobiotics for pre-cancerous lesions, were significantly high
      (p<0.01) in Rajaniganda and Pan Parag Zarda. Isomers of DDT and BHC, which
      principally act on nerves and muscles, were also high (p<0.01) in PM. The
      enhanced metal and mineral content of PM results in massive oral fibrosis. There
      is a high level of narcotics in PM, especially nicotine, a potentially cancerous
      agent in the gastrointestinal tract. CONCLUSION: Experimental studies with
      different extracts of plain and blended PM in mice fed for 16 and 90 days
      revealed no effect on blood and organ weights (kidney, heart, spleen and liver),
      but we did observe attenuated testis. However, in the bone marrow of the mice,
      chromosomes were most affected in the mice fed PM-Zarda blend for 3 months. The
      chromosomal abnormalities included ploidy, loss, breaks, gaps, deletions and
      exchanges in ring chromosomes. The PM caused sperm head anomalies (narrow, blunt,
      triangular and banana shapes), and the sperm were irregular, amorphous, tailless
      and rudimentary, with the maximum effect among the groups fed PM for 3 months.
      Significantly higher levels (p<0.01) of testis glycogen, cholesterol and protein
      were found. The group fed for 16 days showed no change in red blood corpuscles
      (RBC), white blood corpuscles (WBC), hemoglobin and erythrocyte sedimentation
      counts.

PMID- 25610245
TI  - Comparison of surface swab and quantitative biopsy cultures dependent on isolated
      microorganisms from burn wounds.
AB  - OBJECTIVE: Infections are one of the most important and potentially serious
      complications of burn wounds. Quantitative biopsy cultures are useful for showing
      that a burn wound infection is not present, but these cultures are not useful for
      showing that an infection is present. Swab cultures are used to diagnosis surface
      colonization and may not accurately reflect the organism(s) causing the wound
      infection. MATERIALS AND METHODS: To perform a comparison of surface swab and
      biopsy cultures for isolated microorganisms from burn wounds, 160 biopsy/surface
      swab pairs were collected from 160 patients. RESULTS: Seventy-seven patients
      (48.1%) showed positive micro-organism cultures from the burn wounds; 19.3
      percent had both positive surface cultures and significant bacterial counts from
      the biopsy cultures, whereas 28.8 percent of the patients had only positive
      surface cultures. There was moderate agreement (41%) between the results of
      surface swab and quantitative biopsy cultures used to diagnose burn wound
      infections. Pseudomonas aeruginosa (45.5%) was the most predominantly isolated
      bacteria from the wounds, and there was good concordance between the results of
      the surface swab and quantitative biopsy culture samples (78%). Coagulase
      negative Staphylococci (CNS) and Escherichia coli strains were only isolated from
      the surface swab samples because they are colonizing bacteria. The univariate
      analysis revealed that there were significant associations between the results of
      the positive biopsy cultures and the total surface body area, open flame burns,
      prolonged hospitalization and female gender (p<0.05). CONCLUSION: Surface swab
      and quantitative biopsy cultures have a high rate of concordance in predicting P.
      aeruginosa invasion and the colonization of E. coli and CNS strains in burn
      wounds.

PMID- 25610246
TI  - The prevalence of positive serum anticardiolipin antibodies and asymptomatic
      bacteriuria in women with recurrent abortions.
AB  - OBJECTIVE: The asymptomatic colonization of the urinary tract in pregnant women
      may result in severe medical and obstetric complications. The aim of this study
      was to study the prevalence of asymptomatic bacteriuria in cases of elevated
      levels of the anticardiolipin antibody in women who experience spontaneous
      abortions. MATERIALS AND METHODS: A total of 12 women were enrolled in this case
      control study, including 60 patients with a history of three or more abortions
      and 60 healthy pregnant women. All participants were screened for ACL (IgG) and
      with a urine culture. RESULTS: Overall, 19 (31.7%) patients and seven (11.7%)
      healthy pregnant women were positive for ACL. The mean concentrations were 67.1+/
      27.2 IU/mL in the patients and 17.41+/-6.12 IU/mL in the healthy controls
      (p<=0.05). In the 60 patients, only 17 (28.3%) had significant bacteriuria,
      whereas 5 (8.3%) women in the control group had significant bacteriuria. The
      statistical analysis revealed a highly significant difference. Of the 19 patients
      with a positive elevation of ACL, 11 (57.9%) had significant bacteriuria, and
      eight (42.1%) had non-significant bacteriuria. Six patients had ACL-negative
      results associated with significant bacteriuria. The statistical analysis
      revealed a highly significant difference. CONCLUSION: A high serum
      anticardiolipin level was prevalent in women who experienced recurrent abortions
      associated with asymptomatic bacteriuria.

PMID- 25610247
TI  - Chest circumference as a predictive parameter of computed tomography coronary
      angiography radiation doses from dual-source computed tomography.
AB  - OBJECTIVE: Our aim in this study was to determine the relationship between chest
      circumference and the radiation doses received by breast tissues during Dual
      Source Computed Tomography (DSCT) cardiac scans. MATERIALS AND METHODS: Routine
      cardiac DSCT examinations with similar exposure lengths were applied to 30 female
      patients. The scanogram image, multi-slice helical scan x-ray tube voltage and
      anode-cathode current were adjusted automatically according to attenuation for
      each patient during the scanogram acquisition. The standard protocol was
      otherwise applied to all patients. The 30 patients had an average weight of
      67.8+/-15.3 kg, and the average length of the scanned region was 278.0+/-11.6 mm.
      Radiation doses were calculated from the dose-length product (DLP) and the
      computed tomography dose index (CTDI) scanner data values. The correlations
      between radiation dose and chest circumference were investigated. The level of
      significance was set at p<0.05. RESULTS: For routine cardiac DSCT scans, the
      average values were as follows: total DLP: 715.54+/-317.01 mGycm, CTDIvol:
      40.79+/-19.41 mGy, and effective dose (ED): 17.89+/-7.93 mSv. The chest
      circumference of patients correlates well with their radiation exposure (p<0.01).
      CONCLUSION: The distribution of different tissues throughout the human body may
      vary among races and genders. Because of this, many researchers use body mass
      index (BMI) to set image quality and predict the radiation dose distribution from
      general computed tomography (CT) examinations. Additional anthropomorphic phantom
      studies should be conducted to determine more accurate conversion factors and,
      hence, better ED predictions.

PMID- 25610248
TI  - Tissue damage and oxidant/antioxidant balance.
AB  - The oxidant/antioxidant balance in healthy tissues is maintained with a
      predominance of antioxidants. Various factors that can lead to tissue damage
      disrupt the oxidant/antioxidant balance in favor of oxidants. In this study,
      disruptions of the oxidant/antioxidant balance in favor of oxidants were found to
      be a consequence of the over-consumption of antioxidants. For this reason,
      antioxidants are considered to be of importance in the prevention and treatment
      of various types of tissue damage that are aggravated by stress. 

PMID- 25610249
TI  - Abdominal perfusion computed tomography.
AB  - The purpose of this article is to provide an up to date review on the spectrum of
      applications of perfusion computed tomography (CT) in the abdomen. New imaging
      techniques have been developed with the objective of obtaining a structural and
      functional analysis of different organs. Recently, perfusion CT has aroused the
      interest of many researchers who are studying the applicability of imaging
      modalities in the evaluation of abdominal organs and diseases. Per-fusion CT
      enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it
      can act as an in vivo biomarker of tumor-related angiogenesis. 

PMID- 25610250
TI  - Metoclopramide-induced acute dystonic reaction: a case report.
AB  - The aim of this case report is to draw attention to the frequent occurrence of
      metoclopramide-induced movement disorders. We report a case of an acute dystonic
      reaction to metoclopramide in a patient treated for hepatitis A. Metoclopramide
      can cause severe adverse events, such as an acute dystonic reaction, and should
      be used with caution in patients with infectious diseases. 

PMID- 25610251
TI  - Recurrent port infection due to chryseobacterium indologenes.
AB  - Infections due to Chryseobacterium indologenes (C. indologenes) are rare and
      generally associated with immunosupression and indwelling catheters. We report a
      recurrent port infection caused by C. indologenes. In the first bacteremia
      episode we did not remove the port and only applied antibiotherapy. However, the
      patient presented with bacteremia with the same bacteria and successfully treated
      with antibiotherapy and removal of the port. 

PMID- 25610252
TI  - Interrupted Aortic Arch Associated with AP Window and Complex Cardiac Anomalies:
      Multi Detector Computed Tomography Findings.
AB  - Interrupted aortic arch is a rare congenital malformation of the aortic arch
      defined as a loss of luminal continuity between the ascending and descending
      portions of the aorta. In a simple interrupted aortic arch, only a ventricular
      septal defect and patent ductus arteriosus are observed. We present a rare
      complex form of type A interrupted aorta with an aortopulmonary window, an atrial
      septal defect, a ventricular septal defect, and a patent ductus arteriosus on
      multidetector computed tomography (MDCT) imaging. 

PMID- 25610253
TI  - Computed Tomography-Based SYNTAX Score: A Case Report.
AB  - The SYNTAX score is an angiographic scoring system that is currently used for
      evaluating the complexity of coronary lesions. Its efficiency in both long-term
      prognosis and the selection of treatment modalities has been shown in many
      studies. However, there is little evidence for the use of this scoring system in
      CT angiography, which has become a part of coronary artery disease practice.
      Here, we showed that the SYNTAX score could be used in a feasible way in CT
      angiography. 

PMID- 25610254
TI  - Transverse colon diverticulitis with calcified fecalith.
AB  - Left colonic diverticula are common in Western populations, whereas right colonic
      diverticulosis primarily occurs in Oriental populations. Diverticulitis of the
      transverse colon is very rare, with very few cases reported in the literature.
      Herein, we report a case of transverse colon diverticulitis caused by a calcified
      stone in a 69-year-old female. This was a solitary diverticulum. The signs and
      symptoms of the disease are similar to acute pancreatitis. To the best of our
      knowledge, this is the first report describing the MRI findings of a patient with
      trans-verse colon diverticulitis caused by a calcified stone. 

PMID- 25610255
TI  - A Giant Foreign Body due to Rocket Explosion.

PMID- 25610256
TI  - Effects of boiling dairy products on human brucellosis.
AB  - OBJECTIVE: In this study, we determined the seroprevalence of Brucella in the
      blood of bovine and ovine animals and in the blood of the people who raise these
      animals to produce cheese in two rural counties that use two different methods of
      cheese production in Erzurum Province in Turkey. MATERIALS AND METHODS: Samples
      are taken from 100 bovine animals, 100 ovine animals, 100 young people between
      the ages of 10-20 years and 100 adults between the ages of 20-60 years. The
      samples were tested with the Rose Bengal Plate Test (RBPT), the Serum
      Agglutination Test (SAT), the Coombs' Test and a micro-ELISA. RESULTS: We found
      the following rates of Brucella in the province that makes cheese with raw milk:
      bovine (3.00%), ovine (5.00%), people between 10-20 years of age (2.00%) and
      people between 20-60 years of age (10.00%). However, the corresponding rates in
      the region that makes cheese with boiling milk were 2%, 4%, 1% and 5%,
      respectively. CONCLUSION: The results were analyzed descriptively and in
      comparison to the results from the other region. There was a significant
      difference found between the two regions among the Hinis and Oltu individuals
      aged 10-20 and 20-60 (z=0.6<1.96 with a 95% confidence interval).

PMID- 25610257
TI  - Comparison of intraarticular bupivacaine and levobupivacaine with morphine and
      epinephrine for knee arthroscopy.
AB  - OBJECTIVE: To compare the efficacy of intraarticularly injected bupivacaine with
      levobupivacaine when administered in combination with morphine and adrenaline for
      post-operative analgesia and functional recovery after knee surgery. MATERIALS
      AND METHODS: Sixty American Society of Anesthesiologists physical status I-II
      patients were randomized into three groups: Group B was administered 30 mL
      isobaric 0.5% bupivacaine, 2 mg morphine and 100 MUg adrenaline, Group L was
      administered 30 mL 0.5% levobupivacaine, 2 mg morphine and 100 MUg adrenaline,
      and Group C was administered 30 mL 0.9% NaCl solution into the knee joint by the
      surgeon at the end of surgery. The morphine usage and visual analog pain scores
      were recorded regularly afterwards. We also recorded the time that elapsed before
      each patients' first mobilization, positive response to straight leg raising,
      tolerance to 30-50 degrees  knee flexion, recovery of quadriceps reflexes and
      discharge from the hospital. We also recorded patient and surgeon satisfaction.
      RESULTS: The pain scale values were lower in Groups B and L than in Group C at 2,
      4, 6, 8, 12 and 24 hours post-operatively (all p<0.001). In Groups B and L, the
      time for first analgesic request was longer (p<0.01), the morphine consumption
      was lower (p<0.001), and the duration of morphine usage was shorter (p<0.001).
      The times to positive response to straight leg raising, tolerance to 30-50
      degrees  knee flexion and the first mobilization were shorter in Groups B and L
      (p<0.001 for all). CONCLUSION: After arthroscopic knee surgery, intraarticular
      levobupivacaine combined with morphine and adrenaline decreases analgesic
      requirements, shortens the postoperative duration of analgesic use and hastens
      mobilization as effectively as bupivacaine.

PMID- 25610258
TI  - Prevalence of Blood Brotherhood among High School Students in Erzurum and the
      Effect of Peer-led Education on this Practice.
AB  - OBJECTIVE: This study aimed to assess the prevalence of blood brotherhood (BB) in
      Erzurum, Turkey and to observe the effect of education interventions on this
      risky cultural behavior. MATERIALS AND METHODS: This study was designed as a
      cross-sectional intervention, based on minor interventions through a peer-led
      awareness campaign regarding the transfer of blood-borne diseases through BB
      rites. This study was conducted from February through May 2007 at 29 high schools
      in Erzurum. RESULTS: The study population was 53.8% (n=1,522) males and 46.2%
      (n=1,307) females. The proportion of the students who have participated in BB
      rituals was 24.1% (n=558). There was a statistically significant link between BB
      and a history of having Hepatitis B Virus (HBV) infection, family history of HBV
      and male gender (p<0.05). After the structured peer-led education the intention
      to participate in BB rituals decreased from 30.0% to 20.6% (p<0.001). CONCLUSION:
      The prevention of BB rituals, which can result in the transfer of blood-borne
      diseases, requires urgent public awareness campaigns led by healthcare
      professionals.

PMID- 25610259
TI  - Seroprevalence and Seroconversion Rates of Cytomegalovirus pp65 Antigen and Cord
      Blood Screening of Pregnant Women in Malatya, Turkey.
AB  - OBJECTIVE: The rates of seropositivity, seroconversion and fetal infection with
      human cytomegalovirus were analyzed in pregnant women and newborn cord blood in
      this study. The relationships between maternal age, parity, cytomegalovirus
      serology and polymerase chain reaction results were evaluated. MATERIALS AND
      METHODS: A total of 217 pregnant women attended our pregnancy clinic between
      April 2004 and October 2005. During each trimester, 5 cc of maternal blood was
      obtained and 5 cc of cord blood was collected after birth. An enzyme-linked
      immunosorbent assay (ELISA) was used to assess these samples for the presence of
      human cytomegalovirus protein pp65 antigen (in leukocytes) and cytomegalovirus
      DNA (in plasma). RESULTS: The mean age of the pregnant women in our study was
      28.1+/-5.3 years. No seroconversion was observed. Among the pregnant women, 212
      (97.7%) were IgG positive, and 29 (13.4%) were IgM positive. Five of the pregnant
      women were positive for IgM alone (2.3%), whereas 24 (11.3%) were positive for
      both IgM and IgG. The 29 IgM-positive patients were reevaluated using the
      polymerase chain reaction, and no seropositivity was found. None of the cord
      blood samples were IgM positive, whereas 211 (97.3%) were IgG positive. There was
      no significant correlation between parity and seropositivity (p=0.487). The
      relationship between human cytomegalovirus seropositivity and maternal age was
      evaluated by dividing the pregnant women into two groups, with a cut-off age of
      35 years. There was a significant difference in seropositivity between these two
      groups (p=0.045). CONCLUSION: Clearly, there is no need to screen pregnant women
      for Human cytomegalovirus (HCMV) in the Malatya region. Confirming serology
      results using the polymerase chain reaction and antigenemia testing to detect
      false positive results offers the advantage of avoiding unnecessary invasive
      interventions.

PMID- 25610260
TI  - Prescribing practices of physicians at different health care institutions.
AB  - OBJECTIVE: Irrational pharmacotherapy is a widespread health care problem, and
      knowing the prescription practices of physicians at an institutional level can
      present solutions. This study aimed to investigate whether physicians'
      prescribing patterns showed differences at the level of the health care
      institution. MATERIALS AND METHODS: Photocopies of 3201 prescriptions written at
      primary health care centers (PHCs), public hospitals, private hospitals, and
      university hospitals (UHs) were collected from 10 provinces in Turkey. The
      prescriptions were evaluated according to prescribing indicators, and the details
      of drug utilization were compared for different health care institutions.
      RESULTS: The average number of medicines per prescription was 2.83, and the
      highest average was noted in PHCs (2.96). The average cost per prescription was
      US $51.57, and the highest average cost was found in UHs (US $166.10). The most
      frequently prescribed drug group was different among health care institutions.
      With the exception of UHs, the "cold-cough medicines" were the most frequently
      prescribed medicines at all of the institutions. Thirty-nine percent of the
      prescriptions included antibiotics. CONCLUSION: Despite the similarities between
      the distributions of diagnoses on prescriptions by health care institutions, the
      contents of the prescriptions showed differences. The high levels of
      prescriptions for "cold-cough medicines," whose use is widely debated, and the
      widespread tendency of physicians to prescribe antibiotics suggest that there is
      a growing need for disseminating the principles of rational pharmacotherapy.
      Furthermore, institutional differences must be considered when conducting
      rational pharmacotherapy programs.

PMID- 25610261
TI  - Initial experiences of young cardiologists with balloon-expandable transcatheter
      aortic valve implantation in Turkey: a case series of eleven patients.
AB  - OBJECTIVE: Surgical aortic valve replacement is the gold standard of treatment
      for symptomatic severe aortic stenosis in all age groups. Transcatheter aortic
      valve implantation (TAVI), which is performed by senior interventional
      cardiologists in experienced centers, is an alternative therapy for patients
      considered to be at high risk for surgery. The aim of this study is to describe
      the procedural success and short-term results of TAVI performed by young
      interventional cardiologists in Trabzon, Turkey. MATERIALS AND METHODS: Eleven
      patients, 10 women and 1 man, who were treated by balloon-expandable TAVI through
      transfemoral access between January 2012 and April 2012, were included in the
      study. The clinical and echocardiographic parameters of the patients were
      compared before and three months after the procedure. RESULTS: The median
      calculated logistic EuroSCORE and Society of Thoracic Surgeons (STS) score of
      patients were 28% (24%-34%) and 14% (12%-18%), respectively. The median age of
      the patients was 83 years and ranged from 80-85 years. The mean aortic valve
      pressure gradient and the aortic valve area were significantly improved after
      TAVI. The mean aortic valve pressure gradient was 48 (46-53) mmHg before
      treatment and 20 (16-23) mmHg after treatment (p=0.003). The aortic valve area
      was 0.65 (0.55-0.70) cm(2) before treatment and 1.7 (1.6-1.8) cm(2) after
      treatment. The functional status of the patients improved from NYHA class 3-4 to
      NYHA class 1-2. Intraprocedural mortality was not observed, and the overall 3
      month mortality was 9%. CONCLUSION: TAVI can be performed successfully by young
      cardiologists. In centers with high patient loads, we encourage young
      cardiologists to perform TAVI if they have received the appropriate training and
      to form specialized, cooperating teams with a focus on TAVI.

PMID- 25610262
TI  - Can serum ferritin level predict disease severity in patients with crimean-congo
      hemorrhagic Fever?
AB  - OBJECTIVE: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral disease.
      Several factors have already been suggested to explain the pathogenesis as well
      as predict the disease severity. In our study we aim to investigate the role of
      serum ferritin level as a possible predicting factor of disease severity in these
      patients. MATERIALS AND METHODS: We evaluated all patients with laboratory
      confirmed diagnosis of CCHF who were admitted to Boo-Ali Hospital of Zahedan from
      May 2011 to June 2012. Confirmation of the disease determined using the presence
      of anti- CCHFV IgM in the serum by enzyme-linked immunosorbent assay (ELISA) or
      by polymerase chain reaction(PCR). After ethical approval, patients were
      categorized into two groups of mild and severe disease according to disseminated
      intravascular coagulation (DIC) severity using the scoring system of
      International Society on Thrombosis and Hemostasis (ISTH). Serum ferritin levels
      were evaluated and compared between these two groups. Receiver operating
      characteristic (ROC) curve analysis was performed to assess the optimal cutoff
      value of serum ferritin for predicting the disease severity. RESULTS: A total of
      42 patients (36 men, 6 women, age range: 17-78 years) were included in this
      study, of whom 38% had Persian and 62% had Baloch ethnicity. According to DIC
      severity score, 54.7% of the patients had severe disease and 45.3% had mild
      disease. The area under the ROC curve was 0.896 and 95% CI was 0.801-0.991
      (p<0.0001). A cut-off point of 1060 ng/dL, had a sensitivity of 78.9%, a
      specificity of 87%, a positive predictive value of 6% and a negative predictive
      value of 100%. Positive and negative likelihood ratios for this serum ferritin
      level were 6.05 and 0.24, respectively. CONCLUSION: Increased serum ferritin
      level has a significant positive correlation with disease severity in patients
      with CCHF and can evaluate the prognosis of these patients with a high
      sensitivity and specificity.

PMID- 25610263
TI  - An analysis of the anatomic variations of the paranasal sinuses and ethmoid roof
      using computed tomography.
AB  - OBJECTIVE: To determine the Keros classification and asymmetrical distribution
      rates of the ethmoid roof and the frequency of anatomic variations of the
      paranasal sinuses. MATERIALS AND METHODS: Paranasal sinus scans of 500 patients
      obtained using computed tomography were evaluated retrospectively. Measurements
      were performed using a coronal plan with right-left comparison and with distance
      measurement techniques. The depth of the lateral lamella was calculated by
      subtracting the depth of the cribriform plate from the depth of the medial
      ethmoid roof. The results were classified according to their Keros
      classification. Any asymmetries in the ethmoid roof depth and fovea ethmoidalis
      configuration were examined. The anatomic variations frequently encountered in
      paranasal sinuses (pneumatized middle concha, paradoxical middle concha, agger
      nasi cells, Haller cells, Onodi cells, etc.) were defined. RESULTS: The mean
      height of the lateral lamella cribriform plate (LLCP) was 4.92+/-1.70 mm. The
      cases were classified as 13.4% Keros Type I, 76.1% Keros Type II, and 10.5% Keros
      Type III. There was asymmetry in the LLCP depths of 80% of the cases, and a
      configuration asymmetry in the fovea in 35% of the cases. In 32% of the cases
      with fovea configuration asymmetry, there was also asymmetry in the height of the
      right and left LLCP. The most frequent variations were nasal septum deviation
      (81.8%), agger nasi cells (63.8%), intralamellar air cells (45%), and concha
      bullosa (30%). CONCLUSION: Using the Keros classification for LLCP height, higher
      rates of Keros Type I were found in other studies than in our study. The most
      frequent classification was Keros Type II. The paranasal sinus variations in each
      patient should be carefully evaluated. The data obtained from these evaluations
      can prevent probable complications by informing rhinologists performing
      endoscopic sinus surgery about preoperative and intraoperative processes.

PMID- 25610264
TI  - Ischemia-reperfusion damage.
AB  - Ischemia-reperfusion damage is a complex pathological process that begins with
      tissue anoxia and continues with the production of free oxygen radicals,
      expanding with the inflammatory response. The literature suggests the importance
      of antioxidant and anti-inflammatory treatment to treat ischemia-reperfusion
      related tissue damage. 

PMID- 25610265
TI  - Senior-loken syndrome with rare manifestations: a case report.
AB  - Senior-Loken syndrome refers to a disorder in which there is a combination of
      nephronophthisis and retinal dystrophy. The earliest presenting signs of the
      renal component are polyuria and polydipsia secondary to defective urinary
      concentrating ability. Nephronophthisis progresses to end-stage renal disease
      during the second decade. The retinal lesions are variable, ranging from severe
      infantile onset retinal dystrophy to more typical retinitis pigmentosa. There is
      a spectrum of other associated features, including skeletal, dermatological and
      cerebellar anomalies, observed in this entity. Here, we report a case of Senior
      Loken syndrome associated with small hand (short metacarpals) and madarosis. To
      date, there are no cases reported in the literature describing the association of
      madarosis with this syndrome, and the presence of small hands has been reported
      only once. 

PMID- 25610266
TI  - CT- and Fluoroscopy-Guided Percutaneous Transabdominal Embolization of Type II
      Endoleak.
AB  - We report a case of a 79-year-old male patient who was treated 3 years previously
      at another hospital for an abdominal aortic aneurysm with a maximal diameter of
      80 mm. After the treatment control period, computed tomography imaging revealed a
      type II endoleak and no progression in the size of the aneurysm sac. Selective
      injection of the superior mesenteric artery revealed that the endoleak was filled
      by the inferior mesenteric artery via the marginal artery. However, it was not
      possible to access using retrograde catheterization. We decided to treat the type
      II endoleak percutaneously. Embolization was performed at the tomography table
      using fluoroscopy with a mobile C-arm, and the puncture was performed
      transabdominally because there was no access to the sac via a translumbar
      approach. Under fluoroscopic guidance, various diameter/length coils were
      deployed. Follow-up computed tomography scans confirmed the collapsed aneurysm
      sac. When other conventional endovascular methods have failed, percutaneous
      transabdominal treatment of a type II endoleak with sac enlargement offers an
      alternative treatment method. 

PMID- 25610267
TI  - Indoxacarb-Related ARDS, Neurotoxicity and Orange Urine.
AB  - A 17 year old male developed adult respiratory distress syndrome (ARDS),
      seizures, intravascular hemolysis and peripheral neuropathy following self
      poisoning with a pesticide containing 14.5% indoxacarb. He was managed
      conservatively with fluid management, antibiotics, mechanical ventilation and
      physiotherapy. There is limited data concerning the human toxicity of indoxacarb.
      This case demonstrates that findings from animal studies, such as seizures,
      respiratory distress, and intravascular hemolysis are possible following self
      poisoning in humans. In this patient, partial recovery was achieved following
      supportive care. 

PMID- 25610268
TI  - Unusually high prolactin level for medication-induced hyperprolactinemia: a case
      report.
AB  - Hyperprolactinemia has a number of etiologies, including physiological,
      pathological and pharmacological causes. Hyperprolactinemia is frequently
      associated with the use of certain medications. Patients using medications known
      to cause hyperprolactinemia generally develop a mild form of the condition, and
      the prolactin level rarely exceeds 100 ng/mL in these cases. We report a case of
      a 43-year-old woman with an extremely high prolactin level in medication-induced
      hyperprolactinemia caused by a combination of an antipsychotic (sulpirid) and an
      antidepressant (paroxetine). 

PMID- 25610269
TI  - Bullet in hip joint.
AB  - Recently, hip arthroscopy has become more popular in the diagnosis and extraction
      of intraarticular foreign bodies compared to open surgery. If a foreign object
      such as a bullet is not extracted from the hip joint, it may cause mechanical
      arthritis, infection and systemic lead toxicity. We present the arthroscopic
      excision of a bullet from the hip joint of a 33-year-old male patient who
      sustained a gunshot injury. 

PMID- 25610270
TI  - A popliteal artery entrapment syndrome after by-pass surgery.

PMID- 25610271
TI  - A multi detector computed tomography survey of tracheal diverticulum.
AB  - OBJECTIVE: Tracheal diverticulum (DV) is an incidental finding in thoracic
      computed tomography examinations. Tracheal DV may be associated with chronic
      cough and chronic obstructive pulmonary disease (COPD). A few studies have
      investigated the relationship between tracheal DV and COPD. There is still no
      consensus on the relationship. The purpose of this study was to determine the
      incidence of tracheal DV and its coexistence with bronchial DV and hyperaeration.
      MATERIALS AND METHODS: For the study, 299 patients from a total number of 12 800
      patients who underwent a thoracic computed tomography examination were included.
      Tracheal diverticula were evaluated for localization, size, contour, wall
      thickness and communication with the tracheal lumen. The association of tracheal
      DV with bronchial DV and hyperaeration was also noted. The relationship between
      tracheal DV and hyperaeration was analyzed. RESULTS: Of the 299 patients, a total
      of 412 tracheal diverticula were observed. Out of these, 148 of the tracheal
      diverticula were in females, and 264 of the tracheal diverticula were in male
      patients. The incidence of tracheal DV was determined to be 2.38% in this study.
      In total, 400 of the tracheal diverticula (97.1%) were located at the right
      posterolateral aspect of the trachea, and 320 of the tracheal diverticula were
      associated with hyperaeration. There was no significant relation between the
      tracheal DV and hyperaeration. However, 84 of 412 tracheal diverticula had a
      bronchial DV, and 72 of 84 of these bronchial DV were associated with COPD.
      Statistical analysis indicated a significant correlation with COPD and bronchial
      DV (p<0.05). CONCLUSION: Tracheal DV is often asymptomatic and mostly located in
      the right posterolateral aspect of the trachea. Tracheal DV is more common in men
      than in women. The incidence of tracheal DV was 2.38% in this study. Our data
      demonstrate that there was no significant association between tracheal DV and
      COPD. However, there was a significant association between subcarinal bronchial
      DV and COPD.

PMID- 25610272
TI  - The role of 2-[f-18] fluoro 2-deoxy d-glucose positron emission tomography in the
      preoperative staging of gastric cancer.
AB  - OBJECTIVE: FDG-PET can contribute significantly to the preoperative period of
      patients with planned curative resections or with isolated liver or lung
      metastasis. In this study, we analyze the importance and diagnostic value of FDG
      PET in the preoperative evaluation of gastric cancers by correlating its value
      with computerized tomography (CT). MATERIALS AND METHODS: A prospective study was
      conducted. Abdominal and pelvic CTs were obtained for preoperative staging in
      each patient. Separate stagings were performed according to the findings of
      conventional methods and PET scans, and the results were compared with the
      operative and histological findings. RESULTS: When the patients were evaluated
      according to the pathological stage, eight patients were Stage 1 (26.7%), five
      were Stage 2 (16.7%), eight were Stage 3 (26.7%), and nine were Stage 4 (30%).
      FDG-PET and CT down-staged the disease in eight (26.7%) and twelve (40%)
      patients, respectively. FDG-PET and CT up-staged the disease in two (6.7%) and
      five patients (16.7%), respectively. FDG-PET accurately staged the disease in
      eighteen patients (60%) (p= 0.182). CONCLUSION: To develop highly sensitive
      radioactive tests that show invasive local lymph node and peritoneal metastases,
      more studies in the preoperative staging of gastric cancer are needed. FDG-PET
      indicates a high specificity in the staging of gastric cancer. In patients who
      are planned for curative surgery, FDG-PET provides better staging when used with
      CT.

PMID- 25610273
TI  - Melatonin reduces oxidative stress and cardiovascular changes induced by
      stanozolol in rats exposed to swimming exercise.
AB  - OBJECTIVE: Anabolic-androgenic steroids (AAS) are nominated for clinical use to
      promote protein synthesis in many therapeutic conditions. However, the
      indiscriminate use of AAS is related to hazardous cardiac disturbances and
      oxidative stress. We designed a study to investigate whether prolonged treatment
      with high doses of stanozolol modifies the activities of some antioxidant enzymes
      in the heart in sedentary and trained rats and whether this treatment causes
      alterations of cardiovascular parameters. In addition, the effectiveness of
      melatonin as an antioxidant and as a modulator of the cardiovascular side effects
      of stanozolol (STA) treatment was analyzed. MATERIALS AND METHODS: Thirty male
      Wistar rats were divided into the following six groups: sedentary (S), stanozolol
      sedentary (SS), stanozolol-melatonin sedentary (SMS), trained (T), stanozolol
      trained (ST) and stanozolol-melatonin trained (SMT). The stanozolol-treatment
      rats received 5 mg.kg(-1) by subcutaneous injection before each exercise session
      (5 d.wk(-1), i.e., 25 mg.kg(-1).wk(-1)), while control groups received only
      saline solution injection. The melatonin-treatment groups received
      intraperitoneal injections of melatonin (10 mg.kg(-1)), 5 d.wk(-1) for 6 wk.
      Electrocardiography, blood pressure and antioxidant enzyme activity measurements
      were performed at the end of the experimental period for cardiac function and
      molecular assessment. RESULTS: This is the first time that the in vivo effects of
      melatonin treatment on stanozolol-induced cardiovascular side effects have been
      studied. Stanozolol induced bradycardia and significantly increased cardiac
      superoxide dismutase and catalase activities. Trained stanozolol-treated rats
      experienced an increase in blood pressure and relative heart weight, and they
      developed left cardiac axis deviation. Although melatonin did not prevent cardiac
      hypertrophy in exercised stanozolol-treated animals, it maintained blood pressure
      and cardiac catalase activity, and it prevented stanozolol-induced cardiac
      electrical axis deviation. CONCLUSION: In conclusion, under our experimental
      conditions, chronic stanozolol administration induced mild cardiovascular side
      effects that were partly attenuated by melatonin treatment. However, these
      results showed that the combination of melatonin and exercise could minimize the
      stanozolol side effects in the cardiovascular system.

PMID- 25610274
TI  - Patient-staff safety applications: the evaluation of blue code reports.
AB  - OBJECTIVE: Blue code systems (BCS) are communication systems that ensure the most
      rapid and effective resuscitation when a patient is in respiratory or cardiac
      arrest. A hospital employee faced with the situation of a cardiopulmonary arrest
      (CPA) starts the system by dialing 6666 from any phone in the hospital. We
      created a five-person team that includes a doctor, nurse, anesthesia technician,
      stretcher officer and security guard. The purpose of this study is to share our
      experiences in initiating the use of the BCS in our hospital. MATERIALS AND
      METHODS: In our hospital, the records of calls that were made by Callvision BCS
      were analyzed retrospectively from May 2010 to the end of January 2011. RESULTS:
      A total of 474 calls were made using the blue code system. Of those calls, 402
      (84.5%) were determined to be inappropriate calls. The remaining 72 calls were
      responded to. Of the 72 patients who were treated, 21 were discharged after they
      were hospitalized in the service or intensive care unit, 45 cases resulted in
      exitus, and 5 cases were referred to the Ataturk University faculty of medicine.
      CONCLUSION: The BCS has achieved its goal. The discharge rate of 29.5% that we
      achieved is a successful result.

PMID- 25610275
TI  - The effects of erdosteine and N-acetylcysteine on apoptotic and antiapoptotic
      markers in pulmonary epithelial cells in sepsis.
AB  - OBJECTIVE: This study investigated the frequency of apoptosis in rat pulmonary
      epithelial cells after the injection of an intraperitoneal endotoxin
      lipopolysaccharide (LPS), the effects of LPS on apoptotic (bax, caspase-3) and
      antiapoptotic (bcl-2) markers during lung damage, and the protective effects of
      two known antioxidant agents, erdosteine and N-acetylcysteine (NAC). MATERIALS
      AND METHODS: Male Wistar rats were divided into the following six groups, which
      included nine rats each: two control groups, two LPS-treated groups, one
      erdosteine-treated group (150 mg/kg), and one NAC-treated group (150 mg/kg). LPS
      was injected intraperitoneally at a dosage of 20 mg/kg. Following LPS injection,
      the antioxidants were orally administered. The rats were sacrificed at 24 h after
      LPS administration. The levels of apoptosis in bronchiolar and alveolar cells
      were determined using the TUNEL-staining method. Immunohistochemical staining of
      cytoplasmic bax, caspase-3, and bcl-2 in the epithelial cells was performed.
      RESULTS: Erdosteine and NAC significantly reduced the rate of LPS-induced
      pulmonary epithelial cell apoptosis. The effect of NAC on regulating apoptosis
      was weaker than that of erdosteine. Erdosteine and NAC significantly reduced the
      local induction of bax and caspase 3 and significantly increased the reduced
      local production of bcl-2. CONCLUSION: These findings suggest that erdosteine and
      NAlphaC can effectively protect the lungs from the damaging effects of LPS.

PMID- 25610276
TI  - Episiotomy and the development of postpartum dyspareunia and anal incontinence in
      nulliparous females.
AB  - OBJECTIVE: The impacts of an episiotomy on a woman's sex life and ability to
      relax the pelvic musculature remain largely unknown. The aim of the present study
      was to assess the impact of an episiotomy on the development of postpartum
      dyspareunia and anal incontinence. MATERIALS AND METHODS: A total of 200 patients
      participated in the present study. The patients were grouped as follows: vaginal
      delivery with episiotomy (Group 1, N=100) and Caesarian section (Group 2, N=100).
      An interview, which asked about the presence of dyspareunia or anal incontinence,
      was conducted with the participants at 12 weeks postpartum. RESULTS: The mean age
      (years) of Group 1 was 22.6+/-4.4, and the mean age of Group 2 was 24.1+/-4.6.
      Anal incontinence was detected in 4 patients (4%) in Group 1 and 2 patients (2%)
      in Group 2. Dyspareunia was present in 21 patients (21%) in Group 1 and 8
      patients (8%) in Group 2. No significant differences were detected in the
      severity of anal incontinence between the two groups. The amount of time to the
      first coitus following delivery and the total amount of intercourse was compared
      between the two groups. CONCLUSION: It appears that episiotomies do not lead to
      anal incontinence. However, episiotomies may cause dyspareunia, a condition that
      may negatively affect a women's sex life. Therefore, routine episiotomies are not
      suggested.

PMID- 25610277
TI  - Is a drain required after laparoscopic cholecystectomy?
AB  - OBJECTIVE: Whether drains should be routinely used after laparoscopic
      cholecystectomy is still debated. We aimed to retrospectively evaluate the
      benefits of drain use after laparoscopic cholecystectomy for non-acute and non
      inflamed gallbladders. MATERIALS AND METHODS: Two hundred and fifty patients
      (mean age, 47+/-13.8 years; 200 females and 50 males) who underwent laparoscopic
      cholecystectomy for cholestasis were included in the study. The medical files of
      the patients were examined retrospectively to obtain data on patient
      demographics, cholecystitis attacks, complications during the operation, whether
      a drain was placed in the biliary tract during the operation, etc. The volume of
      the fluid collection detected in the subhepatic area by ultrasonography on the
      first postoperative day was recorded. RESULTS: Drains were placed in 51 patients
      (20.4%). The mean duration of drain placement was 3.1+/-1.9 (range 1-16) days.
      Fluid collection was detected in the gallbladder area in 67 patients (26.8%). The
      mean volume of collected fluid was 8.8+/-5.2 mL. There were no significant
      effects of age, gender, and previous cholecystitis attacks on the presence or
      volume of the fluid collection (P>0.05 for all). With regard to the relationship
      between fluid collection and drains, 52 of 199 (26.1%) patients without drains
      had postoperative fluid collection, compared to 15 of 51 (29.4%) patients with
      drains (P>0.05). CONCLUSION: In conclusion, there is no relationship between the
      presence of a drain after laparoscopic cholecystectomy and the presence of
      postoperative fluid collection. Thus, in patients without complications, it is
      not necessary to place a drain to prevent fluid collection.

PMID- 25610278
TI  - Comparison of the efficacy between an intravitreal and a posterior subtenon
      injection of triamcinolone acetonide for the treatment of diffuse diabetic
      macular edema.
AB  - OBJECTIVE: To compare the efficacy of an intravitreal injection to a posterior
      subtenon injection of triamcinolone acetonide for the treatment of diffuse
      diabetic macular edema. MATERIALS AND METHODS: Sixty patients with diabetes
      mellitus presenting with diffuse diabetic macular edema were recruited for the
      study. In each patient, one eye received a 4.0 mg (0.1 mL) intravitreal (IVT)
      injection of TA and the other eye was treated with a 40 mg (1.0 mL) posterior
      subtenon (PST) injection of triamcinolone acetonide (TA). We measured the visual
      acuity, the intraocular pressure (IOP) and the thickness of the macula using
      optical coherence tomography (OCT) before treatment and at one, three and six
      months after treatment. RESULTS: Eyes treated with PST showed 1-3 lines of
      improvement in Snellen's acuity from their pre-injection baseline visual status.
      The eyes in the IVT group showed 1-3 lines of improvement in Snellen's acuity in
      80% of the treated eyes, but 20% of the treated eyes did not display any benefit
      at the end of six months. The difference in acuity between an IVT injection and a
      PST injection at six months post-treatment was statistically significant
      (p<0.05). The macular thickness of the eyes treated with an IVT injection was
      significantly reduced after one (222.7+/-13.4 MUm; p<0.001) and three months
      (228.1+/-10.6 MUm; p<0.001) of treatment. The eyes treated with a PST injection
      displayed a slow response and a significant improvement in macular thickness that
      was observed only after three months (231.3+/-10.9 MUm; p<0.001). The difference
      between the eyes treated with an IVT injection (385.2+/-11.3 MUm) and those
      treated with a PST injection (235.4+/-8.7 MUm) was significantly different six
      months after treatment (p<0.001). The IOP of the eyes treated with an IVT
      injection was significantly increased after one (17.7+/-1.1 mm/Hg; p<0.020),
      three (18.2+/-1.2 mm/Hg; p<0.003) and six months (18.1+/-1.320 mm/Hg; p<0.007)
      when compared to the baseline value (16.1+/-1.4 mm/Hg). The eyes treated with a
      PST injection displayed no significant increase in IOP after one (16.4+/-1.2
      mm/Hg; p<0.450), three (16.3+/-1.1 mm/Hg; p<0.630) and six months (16.2+/-1.1
      mm/Hg; p<0.720) when compared to the baseline value (16.2+/-1.3 mm/Hg).
      CONCLUSION: A PST injection is equally effective and safer than an IVT injection
      of TA for the management of diffuse DME.

PMID- 25610280
TI  - Retrorectal/Presacral epidermoid cyst: report of a case.
AB  - Although epidermal cysts are frequently observed throughout the body, they are
      rarely found in the retrorectal/presacral regions. Retrorectal epidermal cysts
      are congenital lesions of ectodermal origin and generally occur in women during
      the reproductive period. In this case report, a 47 year old female patient with
      25 years of complaint of a mass extending from the perianal region to the retro
      coccygeal region is discussed. A total mass excision with paracoccygeal incision
      was performed under spinal anesthesia. The histopathologic examination
      demonstrated an epidermal cyst. Correct diagnosis and appropriate treatment when
      first detected significantly decrease the recurrence and complication risks in
      all retrorectal tumors. Any mass should be completely removed in the treatment. 

PMID- 25610281
TI  - A cause of renal dysfunction: a giant bladder stone.
AB  - Bladder stones are frequently seen in elderly men and account for 5% of all
      urinary stones. They develop secondary to infravesical obstructions, such as
      prostatic hyperplasia and neurogenic bladder. A 56-year-old patient with frequent
      and painful urination, dysuria, and minor complaints of suprapubic pain was
      referred to our clinic. He was diagnosed with bladder stones by non-contrast
      abdominopelvic computerized tomography, kidney-ureter-bladder radiography, and
      urinary system ultrasonography. Cystolithotomy was applied on a giant stone
      measuring 11*6.5*10 cm that filled the intravesical cavity nearly completely.
      Here, we present this case of a giant bladder stone causing renal dysfunction
      within the context of findings in the literature. 

PMID- 25610279
TI  - Repetitive transcranial magnetic stimulation for clinical applications in
      neurological and psychiatric disorders: an overview.
AB  - Neurological and psychiatric disorders are characterized by several disabling
      symptoms for which effective, mechanism-based treatments remain elusive.
      Consequently, more advanced non-invasive therapeutic methods are required. A
      method that may modulate brain activity and be viable for use in clinical
      practice is repetitive transcranial magnetic stimulation (rTMS). It is a non
      invasive procedure whereby a pulsed magnetic field stimulates electrical activity
      in the brain. Here, we focus on the basic foundation of rTMS, the main
      stimulation parametters, the factors that influence individual responses to rTMS
      and the experimental advances of rTMS that may become a viable clinical
      application to treat neurological and psychiatric disorders. The findings showed
      that rTMS can improve some symptoms associated with these conditions and might be
      useful for promoting cortical plasticity in patients with neurological and
      psychiatric disorders. However, these changes are transient and it is premature
      to propose these applications as realistic therapeutic options, even though the
      rTMS technique has been evidenced as a potential modulator of sensorimotor
      integration and neuroplasticity. Functional imaging of the region of interest
      could highlight the capacity of rTMS to bring about plastic changes of the
      cortical circuitry and hint at future novel clinical interventions. Thus, we
      recommend that further studies clearly determine the role of rTMS in the
      treatment of these conditions. Finally, we must remember that however exciting
      the neurobiological mechanisms might be, the clinical usefulness of rTMS will be
      determined by its ability to provide patients with neurological and psychiatric
      disorders with safe, long-lasting and substantial improvements in quality of
      life. 

PMID- 25610282
TI  - Renal leiomyoma: ultrasonography and computed tomography features with
      histopathologic correlation.
AB  - Renal leiomyomas are not uncommon mesenchymal neoplasms of the kidney, found in
      5% of autopsy specimens and comprising 0.3% of all treated tumors. These tumors
      arise from the smooth muscle cells of the kidney and are mostly located in the
      renal capsule. Typical imaging features of renal leiomyomas include a peripheral
      location, well-defined margins, and hyperattenuation on nonenhanced computed
      tomography (CT) images. The differential diagnosis of renal leiomyomas includes
      benign and malignant solid neoplasms of the kidney. Familiarity with typical
      renal leiomyoma imaging findings may help in the management of these patients and
      prevent unnecessary surgery. 

PMID- 25610283
TI  - An Unusual Initial Presentation of Sjogren's Syndrome: Severe Hypokalemic
      Paralysis Secondary to Distal Renal Tubular Acidosis.
AB  - Sjogren's syndrome is mainly affects the exocrine glands. Patients usually
      complain of persistent dryness of the mouth and eyes. However, nonexocrine organs
      such as the kidneys are often affected in these patients. Distal renal tubular
      acidosis (dRTA) and interstitiel nephritis are common in Sjogren's syndrome.
      Nonetheless, severe hypokalemia and paralysis secondary to dRTA are unusual
      initial manifestation of Sjogren's syndrome. Here, we describe a case of a 48
      year old women admitted to the emergency setting with severe hypokalemic
      paralysis and diagnosed Sjogren's syndrome. 

PMID- 25610284
TI  - A rare cause of childhood ileus: giant mesenteric lipoma and a review of the
      literature.
AB  - Mesenteric lipomas are benign tumors of mature fat cells. They are usually
      asymptomatic and create a clinical picture that depends on the localization and
      size of the lipoma. Although rare, unusually large mesenteric giant lipomas can
      cause partial or complete bowel obstruction. Lipomas resulting in partial bowel
      obstruction can present with symptoms such as intermittent abdominal pain and
      abdominal distention. With complete obstruction, a child can present with an
      acute abdomen. Treatment is the excision of the mass along with the affected
      portion of bowel. In this case study, a 2-year-old female presented with a bowel
      obstruction due to the presence of a giant mesenteric lipoma. Clinical features
      of 16 cases published in the English literature to date are presented. 

PMID- 25610285
TI  - An atypical mesenteric-saphenous collateral portosystemic pathway in a cirrhotic
      patient.

PMID- 25610286
TI  - The Relationship between the Localization, Size, Stage and Histopathology of the
      Primary Laryngeal Tumor with Neck Metastasis.
AB  - OBJECTIVE: In this study we aimed the investigate the laryngectomy (partial and
      total) and neck dissection (functional, radical) in patients undergoing larynx
      identified as a result of the operation of primary tumour localization, size,
      stage and histopathology of the relationship between neck metastasis. MATERIALS
      AND METHODS: The files of 118 patients who has had operation of laryngectomy
      (partly, total) and neck dissection (functional, radical) because of larynx
      cancer in the Ear Nose and Throat (ENT) Clinic in the last ten years (1997-2007)
      have been evaluated retrospectively. RESULTS: 116 of them were male and 2 of them
      were female. Age average was 56+/-22. 189 neck dissections have been applied to
      118 patients. While in supraglottic tumours, 55.2% cervical metastasis and 28.9%
      occult metastasis have been determined, in transglottic tumours 35.1% cervical
      metastasis and 18.9% occult metastasis have been determined. It has been seen
      that while the cervical metastasis ratio of tumours bigger than 4 cm is 55.8%,
      the tumours smaller than 4 cm is 27.27% (p=0.002). The cervical metastasis rate
      has been determined as 26.3% in T1 cases, 25.8% in T2 cases, 40.6% in T3 cases
      and 58.3% in T4 cases. In tumours with advanced T stage, the rate of cervical
      metastasis has been seen more than the ones with early T stage (p=0.027).
      Cervical metastasis has been determined as 27.3% in good differential (G1)
      tumours, 53.4% in medium differential (G2) tumours, and 74.1% in bad differential
      (G3) tumours (p=0.005). CONCLUSION: Considered in the light of clinical
      parameters specified in the cervical lymph node metastasis, N0 patients with
      laryngeal cancer, tumour, according to the anatomical location as unilateral or
      bilateral elective neck dissection should be performed and histopathological
      specimens taken in the event of a positive detection of metastases concluded that
      postoperative radiotherapy should be performed.

PMID- 25610287
TI  - Willingness to Receive the Influenza A(H1N1) Vaccine and its Determinants among
      University Students during the 2009 Outbreak in Turkey.
AB  - OBJECTIVE: The study aimed to determine the willingness to receive the Influenza
      A(H1N1) vaccine and its determinants in a large group of university students.
      MATERIALS AND METHODS: This is a self-administered questionnairre based cross
      sectional study. Students being educated at health and non-health faculties were
      invited to participate in this attitude survey. RESULTS: A total of 974 students
      were included in the study, of whom 51.3% (n=500) were in health related
      faculties. The rate of willingness to receive the Influenza A(H1N1) vaccine was
      11.9 and 7.5% for health and non-health groups, respectively (p<0.05). For the
      health group, having been vaccined with seasonal influenza was a significant
      determinant of being willingness to receive the Influenza A(H1N1) vaccine (O.R
      [95% C.I.]), (O.R: 2.9 [1.5-5.6]) and to believe that the Influenza A(H1N1)
      vaccine prevents swine flu (O.R: 1.7 [1.09-2.8]). For the non-health group, the
      only determinant was to believe that Influenza A(H1N1) vaccine prevents from
      swine flu (O.R: 19.1 [5.7-64.1]) which found to be affected by confusing news in
      media. CONCLUSION: The public health professionals who will organize the efforts
      to improve the acceptability of Influenza A vaccines during influenza outbreaks
      should try to increase the vaccination rates of seasonal influenza. Information
      provided by the media should be organized in order not to cause fear and
      confusion, which was shown to decrease willingness and belief in the Influenza
      A(H1N1) vaccine.

PMID- 25610288
TI  - Factors affecting hypocalcaemia following total thyroidectomy: a prospective
      study.
AB  - OBJECTIVE: After thyroidectomy hypocalcaemia is the most significant complication
      for clinicians. In this study, we investigated the factors associated with
      development of hypocalcaemia after thyroidectomy. MATERIALS AND METHODS: We
      investigated the patients prospectively for age, gender, preoperative diagnosis,
      hormonal status, operative time, operating surgeon, existence of parathyroid
      gland injury at the operation, parathyroid gland auto-transplantation,
      preoperative use of anti-thyroid drugs and amount of bleeding at the operation.
      After operation in 1 and 2 days, serum calcium and phosphor, and in the 1 day
      parathyroid hormone values were evaluated. The chi-square test was applied in the
      analysis of categorical variables. Logistic regression model was used to
      determine the risk of hypocalcaemia in the univariate analysis. RESULTS:
      Hypocalcaemia developed in 47 of 196 patients. Female gender, preoperative
      diagnosis of thyroid cancer and toxic nodular goitre, <3cm nodule size,
      parathyroid injury and auto-transplantation and low vitamin D levels were factors
      found to be associated with hypocalcaemia in the Logistic regression analysis.
      CONCLUSION: The factors associated with hypocalcaemia were defined to be "gender,
      preoperative diagnosis, parathyroid gland injury, nodule size and vitamin D
      deficiency", it is a multifactorial problem and it would not be proper to define
      a few etiological factors.

PMID- 25610289
TI  - Incidental pancreatic lipomas diagnosed by computed tomography.
AB  - OBJECTIVE: Fatty tumours of the pancreas are rarely reported. With the advent of
      the imaging techniques, diagnosis of such tumours based on radiologic imaging is
      increasing. MATERIALS AND METHODS: Between June 2006 and June 2012, four patients
      with pancreatic lipomas that were diagnosed by computed tomography were reviewed
      retrospectively with regard to their imaging findings. There were 3 male and one
      female patient with a mean age of 60.8 years (from 53 to 67 years). RESULTS: A
      single well-bordered nodular fatty lesion with well-delineated thin homogeneous
      capsule was seen in all patients. The mean densitometric measurement of the
      lesions was -76 Hounsfield units (HU) (from -83 HU to -63 HU). The size of the
      lesions was from 7 mm to 12 mm with a mean of 8.75mm. They were located in the
      tail, body and neck of the pancreas in two, one and one patient, respectively.
      There was no associated pancreatobiliary pathology. Histopathologic evaluation
      was not planned because of their incidental diagnosis in these asymptomatic
      patients. CONCLUSION: Pancreatic lipomas are silent lesions, incidentally found
      during imaging procedures. They have specific computed tomography findings and do
      not require any additional diagnostic imaging.

PMID- 25610290
TI  - Investigation of In Vitro Activity of Five Antifungal Drugs against Dermatophytes
      Species Isolated from Clinical Samples Using the E-Test Method.
AB  - OBJECTIVE: Dermatomycosis is an infection with fungi related to the skin:
      glabrous skin, hair and/or nails. Oral treatment of fungal infections in
      dermatology has become a preferred modality for the management of these very
      common conditions. Although there are increasing numbers of antifungals available
      for treatment of dermatophytes, some cases and relapses have been unresponsive to
      treatment. The determination of fungus in-vitro antifungal susceptibility has
      been reported to be important for the ability to eradicate dermatophytes. It is
      necessary to perform antifungal susceptibility testing of dermatophytes. E-test
      (AB Biodisk, Sweden) is a rapid, easy-to-perform in-vitro antifungal
      susceptibility test. The aim of this study was to investigate the susceptibility
      of the different species of dermatophyte strains isolated clinical specimens to
      five antifungal agents using the E-test method. MATERIALS AND METHODS: A total of
      66 specimens were collected from the nails, feet, inguinal region, trunk and
      hands. These strains tested MIC endpoints of E-test for amphotericin B,
      fluconazole, itraconazole, caspofungin, and ketoconazole were read after 72, and
      96 hours incubation for each strain on RPMI 1640 agar. RESULTS: The dermatophytes
      tested included Trichophyton rubrum 43 (65.1%), Trichophyton mentagrophytes 7
      (10.7%), Microsporum canis 5 (7.6%), Trichophyton tonsurans 5 (7.6%),
      Epidermophyton floccosum 4 (6.0%) and Trichophyton violaceum 2 (3.0%). The most
      active agent against all dermatophytes species was caspofungin with a minimal
      inhibitory concentration (MIC) range (MUg/mL(-1)) (0.02-3, 0.032-4, 0.125-0.50,
      0.032-2, 0.25-0.50, 0.125-0.50) and it raconazole with an MIC range (MUg/mL(-1))
      (0.038-1.5, 0.094-1.5, 1-32, 0.016-0.50, 0.25-0.50, 0.125-0.50). The least active
      agent was fluconazole with an MIC range (MUg/mL(-1)) (0, 19-48, 2-256, 2-8, 256,
      256, 8-24). CONCLUSION: E-test seems to be an alternative method to MIC
      determination of antifungal drugs for dermatophytes species, since it is a less
      laborious methodology and results could be obtained faster.

PMID- 25610291
TI  - The intra-umbilical approach in umbilical hernia.
AB  - OBJECTIVE: To investigate the "intra-umbilical incision", a smaller incision
      compared to classic incisions, in cases of umbilical hernia, and which we believe
      will contribute to patient satisfaction in aesthetic terms, and also the
      practicability of such operations. MATERIALS AND METHODS: The umbilical margins
      of eight patients with an umbilical hernia were marked between the levels of 6
      and 12 o'clock, and a median intra-umbilical skin incision was performed between
      these two points. In some cases, where exploration could not be performed
      sufficiently, the incision was extended horizontally from 6 or 12 o'clock. Hernia
      repair and mesh placement was then performed using an intra-umbilical approach.
      RESULTS: Patients were investigated according to the defect size and requirement
      for intra-umbilical incision extension. No requirement for intra-umbilical
      incision was encountered in six patients with a facial defect diameter smaller
      than 4 cm, while the incision had to be extended in two patients with defects
      greater than 4 cm. CONCLUSION: The intra-umbilical approach in umbilical hernia
      surgery is aesthetically superior to classical approaches and is a practicable
      technique.

PMID- 25610292
TI  - Predictors of recurrence in hepatitis C virus related hepatocellular carcinoma
      after hepatic resection: a retrospective cohort study.
AB  - OBJECTIVE: Egypt is one of the hot spots in the international map of
      Hepatocellular carcinoma (HCC), which is where hepatitis C virus (HCV) infection
      is the major risk factor in development of HCC (80%). Due to low organ donation
      rates and lack of deceased liver transplantation, hepatic resection is the main
      line of treatment for HCC patients with sufficient liver reserve. We introduce
      our experience with patients who had HCV related HCC who underwent hepatic re
      section to determine various predictors of tumour recurrence in this group. This
      is the first study to come from a country where chronic HCV hepatitis is endemic.
      MATERIALS AND METHODS: This is a retrospective cohort study of 208 cases of HCC
      in hepatitis C virus positive patients with cirrhotic livers who underwent first
      time liver resection, in Gastroenterology Surgical Centre, Mansoura University,
      Egypt during the period from January 2002 to December 2011. Shapiro-Wilk test was
      used to assess normality of data. Predictors of HCC recurrence were assessed by
      bivariate correlation tests, univariate analysis using the chi-square and t-test
      and binary logistic regression analysis. A P value <0.05 was considered
      statistically significant. RESULTS: Tumour recurrence occurred in 88 patients
      (42.3%). Most of the recurrences occurred within the first year 55 patients
      (62.5%). The most common site for recurrence was the liver (n=68, 77.3%). Based
      on the univariate analysis; significant variables predicting tumor recurrence
      were alpha feto-protein (AFP), blood transfusion, multi-focality, cut margin,
      microvascular invasion, lack of capsule, tumour grade and stage. Based on
      multivariate analysis, the main variables predicting tumor recurrence were blood
      transfusion, cut margin, tumour capsule and microvascular invasion. CONCLUSION:
      Although the predictors of recurrence are the same for both HBV and HCV related
      HCC, the rate and aggressiveness of recurrence are higher in HCV related HCC.

PMID- 25610293
TI  - Somatosensory evoked potential findings in ankylosing spondylitis.
AB  - OBJECTIVE: Somatosensory evoked potential (SSEP) abnormalities were reported in
      patients with ankylosing spondylitis (AS). This study aimed to investigate SSEP
      abnormalities and its relation with clinical findings in AS patients. MATERIALS
      AND METHODS: The study included 26 patients with AS and 17 age-matched health
      volunteers (Control for SSEP). Median nerve SSEP findings were normal in all AS
      cases. RESULTS: However, delayed latency and/or very low amplitude of tibial
      nerve SSEP was found in 20 (76.9%) AS patients. There were significant
      correlations between tibial SSEP latency and disease duration (R=0.433 to 0.635).
      There was also an inverse correlation between tibial SSEP amplitude and disease
      duration (R=-0.429, p=0.047). Serum estradiol level, hip total bone mineral
      density, The Bath Ankylosing Spondylitis Functional Index (BASFI) score and Beck
      depression score were significantly lower in AS patients with SSEP abnormalities
      (37.3+/-10.8 pg/mL, 0.916+/-0.123 g/cm(2), 35.0+/-27.9, 12.8+/-8.4, respectively)
      than in AS patients without SSEP abnormalities (53.7+/-12.3 pg/mL, 1.103+/-0.197
      g/cm(2), 64.8+/-15.5, 24.8+/-10.1, respectively). CONCLUSION: Significant inverse
      correlations between SSEP latencies and dehydroepiandrosterone sulphate (DHEAS)
      levels were found (R=-0.400 to -0.713). There were also significant inverse
      correlation between SSEP latencies and DHEAS/oestrogen index (R=-0.596 to 
      0.868), and between SSEP latencies and DHEAS/Progesterone index (R=-0.467 to 
      0.685). As a conclusion, this study indicates that tibial nerve SSEP
      abnormalities are common in patients with AS and there are significant
      correlations between clinical findings of AS and SSEP abnormalities.

PMID- 25610294
TI  - Economic impact of blood transfusions: balancing cost and benefits.
AB  - Blood transfusions may be lifesaving, but they inherit their own risks. Risk of
      transfusion to benefit is a delicate balance. In addition, blood product
      transfusions purchases are one of the largest line items among the hospital and
      laboratory charges. In this review, we aimed to discuss the transfusion
      strategies and share our transfusion protocol as well as the steps for hospitals
      to build-up a blood management program while all these factors weight in.
      Moreover, we evaluate the financial burden to the health care system. 

PMID- 25610295
TI  - Plasmodium vivax infection impersonating Plasmodium falciparum malaria.
AB  - A 73-year-old woman came to the casualty ward with symptoms of syncopal attacks,
      weakness, fever with chills and rigors. A provisional diagnosis of Plasmodium
      vivax malaria was made after the blood investigations. She had deranged renal
      function tests, altered sensorium and low platelet count. Repeated tests for P.
      falciparum (Card test) were negative. Glucose-6-Phosphate dehydrogenise (G6PD)
      levels were within normal limits. Treatment for P. vivax was started with
      intravenous quinine initially followed by oral quinine for a period of seven days
      and patient responded to the treatment and was discharged within 2 weeks of
      admission. Most of the cases of P. vivax present with typical and predictable
      features, although atypical cases with characteristics of P. falciparum can
      occur, especially in the elderly. 

PMID- 25610296
TI  - Non-functioning Aortocaval Paraganglioma Masquerading as Celiac Lymphnodal
      Metastasis.
AB  - An extra-adrenal paraganglioma is a rare tumour derived from chromaffin cells of
      sympathetic ganglia. This report documents a rare case of a non-functional
      aortocaval paraganglioma in a 24-year-old woman with persistent abdominal pain.
      Computed tomography revealed a solid mass, measuring 2.5x3cms, localized between
      the celiac trunk and superior mesenteric artery in aortocaval location along with
      right ovarian cystic mass. A clinical diagnosis of malignant ovarian tumour with
      celiac nodal metastasis was made. Excision and pathological analysis of both
      revealed an aortocaval extra-adrenal paraganglioma and benign ovarian cyst. On
      serial follow-up the patient was in a good health, asymptomatic and without
      evidence of tumour recurrence. This case emphasizes the necessity of including
      extra-adrenal paraganglioma in the differential diagnosis and management of
      retroperitoneal tumours, despite its rarity. 

PMID- 25610297
TI  - A rare manifestation of achalasia: huge esophagus causing tracheal compression
      and progressive dyspnea.
AB  - Achalasia is a primary esophageal motility disorder characterized by the absence
      of primary peristalsis and a failure of the lower esophageal sphincter to relax,
      resulting in a dilated esophagus. Dysphagia is the classic and most common
      symptom. Respiratory obstruction due to tracheal compression caused by a
      massively dilated esophagus is a very rare but fatal complication. Herein, we
      report a case of a patient with long-standing achalasia who had tracheal
      compression secondary to a markedly dilated, giant esophagus. These findings are
      documented with CT scans. His symptoms regressed after a Heller myotomy and
      fundoplication operation. 

PMID- 25610298
TI  - Hypertrophic columns of bertin: imaging findings.
AB  - Hypertrophic column of Bertin (HCB) may mimic renal mass and may lead to
      unnecessary nephrectomy in some conditions. In this case report we present a
      patient with HCB, which mimics renal mass in ultrasonography (US) examination
      with its US, Doppler US and magnetic resonance imaging (MRI) findings. In
      contrast to the US, excretory urography (EU) and computed tomography (CT)
      findings of HCB, MRI findings of this entity could not take part in the
      literature sufficiently. We suggest that this case report could be useful in
      preventing the unnecessary biopsy and surgical procedures. In conclusion,
      however, US is often sufficient in the diagnosis of HCB, unusual lesions could be
      seen. In the final diagnosis of these lesions, MRI is very useful and more
      responsive technique. Understanding the imaging characteristics of HCB could
      prevent unnecessary interventional or surgical procedures. 

PMID- 25610299
TI  - A Cystic Mass does not Always Mean Hydatid Cyst in Endemic Areas.
AB  - Within the medical community, there is a tendency to describe all cystic lesions
      in the liver and lungs as Hydatid disease (HD) in areas with HD endemics. This
      approach may sometimes cause a misdiagnosis. We have three cases with children
      aged between seven, seven and ten year old, all of whom had been diagnosed, via
      radiologic imaging, with HD cysts and started on treatment without confirmation.
      The true diagnoses of these cases were undifferentiated embryonal sarcoma (UES)
      in two and oesophageal duplication in one case, respectively. The indirect
      haemagglutination assays (IHA) were obtained in two of them. Although their
      results were negative, albendazole treatment was started in all cases.
      Confirmatory tests should be run in dubious cases. An IHA test can aid the
      diagnosis, although its effectiveness is limited. The possibility of false
      positive and negative results always exists, especially in lung cysts. A
      percutanous biopsy is strongly advised for differential diagnosis. 

PMID- 25610300
TI  - Displaced mousseau-barbin tube: a rare cause of dysphasia.

PMID- 25610301
TI  - Erectile Dysfunction among Yemenis: Does Chewing Khat Play a Role?
AB  - OBJECTIVE: Khat, a type of plant that grows in Yemen and some African countries
      like Somalia, Ethiopia and Kenya, is considered to be addictive and contains some
      stimulating substances that may affect different body organs. This study was
      conducted to identify the causes of erectile dysfunction (ED) and to investigate
      the effect of chewing Khat on this disease in Yemenis. MATERIALS AND METHODS: A
      total of 236 patients who were treated at University of Science and Technology
      Hospital and complained of ED were examined with penile Doppler ultrasonography
      (US). Biodata and health data were collected from the patients' records and via
      mobile interviews. RESULTS: The causes of ED were psychological causes (72%),
      venous leakage (19%) and arterial disease (9%). Psychological ED was most common
      in 15-29-year-olds, while pathological ED increased with increasing age
      (p=0.041). Heart diseases and diabetes showed a significant association with
      pathological ED (p<0.05). Although 81% of the ED patients in this study chewed
      Khat, there was no significant association between chewing Khat and either
      pathological or psychological ED (p>0.05). CONCLUSION: Psychological problems are
      the main causes of ED among Yemenis especially in the younger age group. It is
      too early to exclude Khat as a factor contributing to this health problem, and
      this topic warrants further case-control studies with a larger sample size.

PMID- 25610302
TI  - A comparison of two different culture methods for use in the diagnosis of
      pulmonary tuberculosis.
AB  - OBJECTIVE: Tuberculosis (TB) continues to be a significant health problem
      worldwide. Pulmonary TB is a contagious disease. To control the spread of TB, the
      disease must be diagnosed early and treated effectively. MATERIALS AND METHODS:
      In this study, we determined the rates and periods of TB bacterial reproduction
      using the Lowenstein-Jensen (LJ) and the Mycobacterium Growth Indicator Tube
      (MGIT) culture systems in respiratory specimens obtained from 105 suspected TB
      cases that applied to our service. RESULTS: Using either the LJ or MGIT method,
      the reproduction rates of TB cultures from 91 positively diagnosed cases were
      determined to be 69.2% and 92.3% (p=0.116), respectively. The reproduction period
      for these same cultures was determined to be 29.7+/-10.0 days and 12.1+/-6.1 days
      (p<0.0001), respectively. The culture positivity rate determined using both the
      LJ and MGIT methods together was found to be significantly higher than the rate
      determined using either LJ or MGIT separately (p<0.0001). CONCLUSION: For the
      early diagnosis of pulmonary tuberculosis, which is essential for controlling the
      spread of TB, the routine use of the MGIT system, which is a rapid, automated and
      non-radiometric method, combined with the LJ method would effectively increase
      the diagnosis rate in order to control tuberculosis outbreaks.

PMID- 25610303
TI  - Prevalence of Tension-Type Headache in Individuals Aged between 18-65 Years in
      the Eastern Parts of Turkey.
AB  - OBJECTIVE: Although tension-type headache (TTHA) is one of the most frequently
      encountered diseases in the general population, relatively few studies have been
      conducted on this health condition. The published data are limited on the
      frequency of TTHA in Turkey, and no studies to date have been initiated on the
      prevalence of TTHA in the city of Erzurum or the Eastern Anatolian Region.
      MATERIALS AND METHODS: The study was conducted using in-depth interviews from
      1972 individuals from city of Erzurum. TTHA was queried in patients with a
      history of headache, according to the International Classification of Headache
      Disorders diagnostic criteria, and the frequency of TTHA was investigated.
      RESULTS: A total of 1972 patients were enrolled in this study. The frequency
      reached a peak between the ages of 40-49 years (35%), and it significantly
      declined after the age of 49. During an examination (palpation), cranial muscle
      sensitivity was detected in 33% of the patients. CONCLUSION: The frequency of
      TTHA has been identified as 22.3% in patients between the ages of 18-65. The
      frequency of tension type headache in the city of Erzurum was lower than that in
      the general population of Turkey.

PMID- 25610304
TI  - ERCC1 Expression in Non-Small Cell Lung and Esophageal Cancer.
AB  - OBJECTIVE: "Excision Repair Cross-Complementation Group 1" (ERCC1) enzyme is a
      vitally important basic protein required for DNA repair. Recent studies suggest
      that ERCC1 is involved in resistance to antracycline-based chemotherapy regimens.
      In this study, we aimed to analyze ERCC1 expression in lung and esophageal cancer
      patients. We also aimed to investigate the possible correlation between the ERCC1
      expression levels and patient demographic information. MATERIALS AND METHODS:
      Twenty esophageal and 20 non-small cell lung cancer (NSCLC) patients diagnosed
      between December 2009 and December 2010, via either endoscopic, bronchoscopic or
      tru-cut biopsy, were included in this study. The ERCC1 expression levels were
      analyzed by the reverse transcriptase-polymerase chain reaction (RTPCR) method in
      RNA samples extracted from pathological biopsy specimens. The patient demographic
      information was also recorded. RESULTS: There was no significant correlation
      between the ERCC1 expression level and demographic parameters, including the
      tumor, node, metastatis (TNM) staging, World Health Organization (WHO) grading,
      age, gender, hemoglobin level and albumin level, in the patient groups. The mean
      ERCC1 expression levels in the NSCLC and esophageal cancer patients were 0.71+/
      0.85 and 0.62+/-0.78, respectively. The ERCC1 expression level was elevated in
      15% of each patient group. CONCLUSION: Analysis of the ERCC1 expression in NSCLC
      and esophageal cancer patients prior to chemotherapy would be useful for
      personalized chemotherapy regimens and would provide more accurate prognostic
      information for the patient.

PMID- 25610305
TI  - Relationship between Serum Gamma-glutamyl Transferase Levels with Ascending
      Aortic Dilatation.
AB  - OBJECTIVE: Increased serum gamma-glutamyl transferase levels (GGT) have been
      shown to directly promote oxidative stress. Previous studies have shown the
      relationship between the dilatation of the ascending aorta and oxidative stress.
      This study was designed to examine the relationship between serum GGT
      concentrations with dilatation of the ascending aorta. MATERIALS AND METHODS:
      Ninety patients with ascending aortic dilatation and 90 age-sex-matched patients
      without aortic dilatation were included in the study. The patients were evaluated
      by a complete transthoracic echocardiographic examination including measurement
      of the aortic dimensions, where a diameter of 3.7 cm and above was accepted as
      ascending aortic dilatation. Serum GGT concentration was measured in all
      patients. RESULTS: In the group with aortic dilatation, HT frequency, serum uric
      acid, hs-CRP and GGT levels, the LV mass index, and the left atrial volume index
      were found to be higher than the control group. The logistic regression analysis
      showed that only HT frequency (OR:1.23, 95% CI 1.11-1.35, p value: 0.02), the LA
      volume index (OR: 1.34, 95% CI 1.21+/-1.4, p:0.005) and serum GGT levels (OR:
      1.12, 95% CI 1.01+/-1.20, p:0.03) were found to be independent predictors. There
      was a significant correlation between serum GGT levels and ascending aortic
      diameter (r: 0.268, p<0.001). In the ROC curve analysis, AUC was 0.659 (0.580+/
      0.738) for a 23.5 serum GGT cut-off value (64% sensitivity and 53% specificity).
      CONCLUSION: We found that serum GGT concentration was significantly associated
      with ascending aortic dilatation. Large epidemiological studies are required to
      correlate the findings from this study with clinical outcome.

PMID- 25610306
TI  - Comparison of the mycobacterium growth indicator tube method and the method of
      proportion for drug susceptibility testing of mycobacterium tuberculosis.
AB  - OBJECTIVE: Tuberculosis is an important public health problem in developed and,
      especially, developing countries. The incidence of multi-drug-resistant
      Mycobacterium tuberculosis (MDR-TB) has increased in recent years. Mycobacterial
      culture and susceptibility testing must be rapidly concluded for effective
      treatment and control of the disease. The present study evaluated the reliability
      of the Mycobacterium Growth Indicator Tube (MGIT) method for testing the
      susceptibility of M. tuberculosis to four first-line antimicrobial drugs by
      comparing MGIT results to those obtained by the method of proportion (MOP), which
      served as the reference method. MATERIALS AND METHODS: A total of 60 clinical
      isolates (28 sputum, 7 bronchoalveolar lavage, 7 cerebrospinal fluid, 3 gastric
      aspirates, 5 urine, 4 pleural fluid and 6 other specimens) of M. tuberculosis
      were tested for susceptibility to streptomycin (SM), isoniazid (INH), ethambutol
      (EMB) and rifampin (RIF). MOP was carried out according to National Committe for
      Clinical Laboratory Standards (NCCLS) on Lowenstein-Jensen medium. MGIT
      susceptibility testing was performed according to the protocol provided by the
      manufacturer. RESULTS: Resistance was detected in 18.3% and 16.7% of the isolates
      for INH, 13.3% and 10.0% for RIF, 16.7% and 11.7% for SM and 6.7% and 8.3% for
      EMB by MOP and MGIT, respectively. CONCLUSION: MOP remains the method of choice,
      however, the correlation between MOP and MGIT suggested that MGIT can also be
      used routinely and that it is a reliable method for testing susceptibility of M.
      tuberculosis strains to first-line anti-tuberculosis drugs.

PMID- 25610307
TI  - Early and late-term results of arthroscopic surgery on patients with
      gonarthrosis.
AB  - OBJECTIVE: To provide guidance in the selection of the appropriate patient for
      arthroscopic debridement. MATERIALS AND METHODS: Ninety patients who were
      diagnosed with gonarthrosis according to modified American College of
      Rheumatology (ACR) criteria and who underwent arthroscopic debridement and
      meniscectomy were evaluated. Functional assessment of patients was made based on
      preoperative as well as 1 month and 1 year postoperative results of the Lysholm
      Knee Score and the Visual Analog Scale (VAS). One year postoperatively, the
      Tapper-Hoover Scoring System was used to calculate long-term results. Analyses
      were conducted using SPSS 18 software. For this study ethics committee approval
      was received from the ethics committee of Ataturk University Medical Studies
      Department Head on 08.10.2010 at the 6th meeting with regards to the document
      written on 16.06.2010 with number 998. RESULTS: Differences between preoperative
      and 1-month and 1-year postoperative values in the Western Otorino and McMaster
      Universities Osteoarthrosis (WOMAC) Index, Lysholm and VAS were found to be
      statistically significant (p<0.001) (Table 1). According to Tapper-Hoover
      results, 82.8% of patients benefited from arthroscopic debridement in the long
      term (Table 2). Among body mass index (BMI) groups, the WOMAC, Lysholm and VAS
      values of obese patients were worse than those of normal weight and underweight
      patients, and the difference was statistically significant (p<0.005). Late-term
      results of patients younger than 55 were superior to those over 55. CONCLUSION:
      In the treatment of patients with gonarthrosis, arthroscopic debridement is a
      good option. Patients who have a low BMI and are younger than 55 years old
      experience more benefit from arthroscopic debridement.

PMID- 25610308
TI  - The frequency of complications and the etiology of disease in patients with liver
      cirrhosis in erzurum.
AB  - OBJECTIVE: This study included 100 patients diagnosed with liver cirrhosis who
      presented at Ataturk University Faculty of Medicine Gastroenterology clinic and
      polyclinic. MATERIALS AND METHODS: The etiology of liver cirrhosis and the
      incidence of its complications have been investigated. RESULTS: The etiological
      classification of liver cirrhosis in our patients was as follows: 47 hepatitis B
      virus hepatitis, 11 hepatitis C virus hepatitis, 5 HBV+HDV hepatitis, 4 Budd
      Chiari syndrome, 2 chronic alcohol abuse, 2 ischemic heart disease, 1 autoimmune
      hepatitis, 1 sclerosing cholangitis, 1 hydatid cyst. In 26 patients we could not
      find any etiological condition. These patients were called cryptogenic cirrhosis
      patients.When we examined the complications of liver cirrhosis, it appeared that
      there were ascites in 83 patient. In 56 patients, esophageal variceal bleeding
      occurred. There was spontaneous bacterial peritonitis in 42 patients. Hepatorenal
      syndrome occurred in 26 patients. Finally, in 3 patients we detected hepatorenal
      syndrome. CONCLUSION: The most common causes in the etiology of liver cirrhosis
      are viral, especially HBV. Many of the patients were in decompensated phase when
      diagnosed. We found that there was a close relation between the frequency of
      complications and mortality in liver cirrhosis.

PMID- 25610309
TI  - Comparison of coagulase-negative staphylococci isolated from blood cultures as a
      true bacteremia agent and contaminant in terms of slime production and
      methicillin resistance.
AB  - OBJECTIVE: The aim of this study is to determine the species distribution, slime
      activity, and methicillin resistance of coagulase-negative staphylococci (CoNS)
      isolated from blood cultures as either contaminants or true bacteremia agents.
      MATERIALS AND METHODS: In this study, 13.268 blood culture samples sent to our
      laboratory from various clinics during a two-year period were examined in terms
      of the presence of CoNS to clarify whether the isolates are true bacteremia
      agents, as defined by Centers for Disease Control and Prevention (CDC) criteria.
      The slime activities of true bacteremia agents (58 CoNS strains) and contaminants
      (50 randomly selected CoNS strains) were investigated by the Christensen method.
      The methicillin susceptibilities of the strains were determined by the disk
      diffusion method. RESULTS: Although the frequency of slime production was 39.7%
      among the true bacteremia CoNS agents, it was 18% in CoNS that were judged to be
      contaminants (p<0.05). S. epidermidis was the most frequently isolated species
      for both the true bacteremia agent group (56.9%) and contaminant group (74%).
      Additionally, S. epidermidis was the bacterium most frequently characterized as
      slime producing in both groups. The methicillin resistance of slime-producing
      CoNS was determined to be 82.6% for the true bacteremia agent group and 77.8% for
      the contaminant group. CONCLUSION: The presence of slime activity in CoNS
      isolated from blood culture samples is supportive evidence that they are most
      likely the agents of true bacteremia cases.

PMID- 25610310
TI  - The Relationship between Non-Dipper Blood Pressure and Thoracic Aortic Diameter
      in Metabolic Syndrome.
AB  - OBJECTIVE: Non-dipper hypertension is associated with increased cardiovascular
      morbidity and mortality. The purpose of this study was to evaluate the
      association of non-dipping hypertension with aortic diameter in patients with
      metabolic syndrome. MATERIALS AND METHODS: This study included 70 hypertensive
      patients with metabolic syndrome. These patients were evaluated with 24-h blood
      pressure Holter monitoring and divided into two groups of 35 patients each.
      Aortic diameter was measured by M-mode and two-dimensional echocardiography.
      These parameters were compared between the two groups. RESULTS: In the dipper
      group, there were 26 female and 9 male patients with a mean age of 55+/-11 years.
      In the non-dipper group, there were 25 female and 10 male patients with a mean
      age of 56+/-11 years. No significant difference was found between the two groups
      in terms of basic characteristics. Non-dipper hypertensive patients had a higher
      thoracic aortic diameter value than dipper patients (35.6+/-2.4 and 33.23+/-1.1,
      p<0.01). CONCLUSION: These findings suggest that thoracic aortic diameter value
      is higher in patients with non-dipper hypertension.

PMID- 25610311
TI  - Two-Dimensional Strain Imaging: Basic principles and Technical Consideration.
AB  - Tissue Doppler Imaging (TDI) and TDI-derived strain provide considerably accurate
      information in the non-invasive assessment of local myocardial functions. Given
      its high temporal and spatial resolution, TDI allows assessment of local
      myocardial functions in each phase of cardiac cycle. However, the most important
      limitation of this method is its angle dependence. New techniques to measure
      myocardial deformation, such as speckle tracking echocardiography, overcome the
      angle-dependence limitation of TDI-derived strain. Moreover, these techniques
      provide more unique information about myocardial fiber orientation. This review
      examines the architectural structure and function of the myocardium and includes
      technical revisions of this information that will provide a basis for STE. 

PMID- 25610312
TI  - Diffuse idiopathic calcinosis cutis in an adult: a rare case.
AB  - Idiopathic calcinosis cutis is a condition involving the deposition of calcium
      salts in the skin and subcutaneous tissue. The disease is a pathological
      condition of unknown origin and hence is idiopathic. The salt deposition is
      confined to areas such as the breast and vulva in females and scrotum and penis
      in males. Diffuse calcification with multiple complications in an adult is a rare
      entity. Only one such case has been reported in literature. A 59-year-old female
      presented to us with swelling of the right elbow, multiple calcific nodular
      lesions all over her fingers approximately 0.5x0.5 cm in size, and ulcers on her
      left great toe and right thumb with pain for the past two months. The ulcers were
      2x2 cm and were observed to be healing without active discharge or signs of
      inflammation. The elbow was diffusely swollen and tender. Flexion deformity was
      present at the elbow. X-ray of hand and feet revealed calcinosis of the elbow and
      interphalangeal joints of the foot and hand. Blood tests revealed elevated C
      reactive protein levels of 24 mg/dL, elevated Erythrocyte Sedimentation Rate
      (ESR) of 52 mm/hr., serum calcium of 9.7 mg/dL and a serum phosphorous of 5
      mg/dL. Cultures from the foot ulcer were positive for methicillin-resistant
      staphylococcus aureus (MRSA). Workup for collagen vascular disease was negative.
      Histopathology confirmed calcinosis cutis. Treatment involved a conservative
      approach, including physiotherapy for the flexion deformity, antibiotics for
      MRSA, analgesics for pain relief and daily dressings. This case demonstrates that
      if a patient presents with multiple chalky nodular lesions with or without
      ulceration, pain and discharge involving areas of the upper limb or lower limb,
      diagnosis of idiopathic calcinosis cutis could be considered as a differential,
      despite its common confinement to the scrotum, breast, vulva and penis. 

PMID- 25610313
TI  - Cerebral fat embolism diagnosed by cognitive disorder.
AB  - Fat embolism syndrome is a rarely seen complication of skeletal trauma, and it is
      seen at a rate of 2-5% after fractures of the long bones of the lower
      extremities. Its classic triad-+consists of hypoxemia, petechial bleedings on the
      skin and neurological findings. These neurological findings are highly variable
      and non-specific, and they can present with lethargy, irritability, delirium,
      stupor, convulsion or coma. In this report, a male case is presented who was
      diagnosed with cerebral embolism due to acute cognitive disorder after a
      segmental tibial fracture. 

PMID- 25610314
TI  - Cystic lung disease in birt-hogg-dube syndrome: a case series of three patients.
AB  - Birt-Hogg-Dube syndrome is characterized by clinical manifestations such as
      hamartomas of the skin, renal tumors and lung cysts with spontaneous
      pneumothoraces. Patients with Birt-Hogg-Dube syndrome may present with only
      multiple lung cysts. We report the chest computerized tomography (CT) features of
      three patients with Birt-Hogg-Dube syndrome. Each patient had multiple lung cysts
      of various sizes according to chest CT evaluation, most of which were located in
      lower lobes and related to pleura. The identification of unique characteristics
      in the chest CT of patients with Birt-Hogg-Dube syndrome may provide an efficient
      mechanism for diagnosis. 

PMID- 25610315
TI  - Findings from imaging stercoral colitis associated with colonic perforation.

PMID- 25610316
TI  - Peritonitis incidence was correlated with duration of peritoneal dialysis rather
      than leptin or neutrophil to lymphocyte (n/l) ratio in peritoneal dialysis
      patients.
AB  - OBJECTIVE: End stage renal disease (ESRD) has a high worldwide prevalence and
      incidence. Peritonitis is one of the leading causes of hospitalization in
      peritoneal dialysis patients. Although inflammatory markers show increased
      inflammatory responses, cellular immune response was decreased in ESRD patients.
      Leptin is an adipocyte-derived hormone that has activity in energy, nutrition and
      immune system. Neutrophil to lymphocyte ratio (N/L) was emerged as a predictive
      and prognostic criterion in many instances. In this study, we aimed to
      investigate the relationships between increased inflammation in peritoneal
      dialysis patients and leptin, N/L ratio. MATERIALS AND METHODS: Forty-one ESRD
      patients, who were been at least 12 months of peritoneal dialysis therapy, were
      included in the study. Patients' demographic properties were recorded. Serum
      leptin level, WBC count, C-reactive protein, erythrocyte sedimentation rate and
      biochemical markers were measured. Patients with active viral or bacterial
      infection, malignancy, inflammatory disease, immunosuppressive medication users
      were all excluded from the study. Age and sex-matched healthy control group was
      included in the study only for their leptin levels. RESULTS: The measured mean
      serum leptin level of the patient group was statistically significantly higher
      than control group (1624.88+/-1608.16 and 416+/-439.85). The calculated mean
      peritonitis incidence was 0.041+/-0.047 peritonitis/per year. The number of
      peritonitis attack was significantly correlated with duration of peritoneal
      dialysis, body mass index (BMI), age and presence of cardiovascular disease.
      Serum leptin level was significantly correlated with sex, age, primary cause of
      ESRD, BMI, blood glucose level and duration of peritoneal dialysis (PD).
      CONCLUSION: We detected that ESRD patients have higher serum leptin levels
      compare to healthy adults. Increased leptin was correlated with sex, age, BMI,
      primary cause of ESRD and serum glucose level. Number of peritonitis attack and
      peritonitis incidence was significantly correlated with the duration of PD, BMI
      and sex. We weren't able to show the predictive N/L value in PD patients in case
      of peritonitis.

PMID- 25610317
TI  - The changing rate of suspected rabies bites after begin to act animal shelter in
      erzurum city.
AB  - OBJECTIVE: We aimed to evaluate the relationship between establishing an animal
      shelter in Erzurum and the number of suspected rabies bites between the years
      2005 and 2012. MATERIALS AND METHODS: A retrospective, repeated cross-sectional
      study was planned in Erzurum in the year 2013. Records between the years 2005 and
      2012 were obtained from the Communicable Diseases Department of the Erzurum
      Health Directorate. Data for 5789 cases exposed to suspected rabies bites were
      analyzed. RESULTS: 5789 suspected rabies bites were encountered in Erzurum
      between the years 2005 and 2012. After establishing the animal shelter in 2009,
      4239 dogs were collected from the streets within four years and 426 of them were
      released after immunization. Additionally, the following services were given in
      the animal shelter between 2009 and 2012: immunization of 2935 dogs,
      sterilization of 1735 dogs, and release of 2082 dogs back to the street. 4-years
      before the establishment of the animal shelter, the number of dog-bites had
      decreased from 3403 cases to 2386 cases; 4-years after the establishment of the
      shelter, it declined by 29.8%. While there were 1096 suspected rabies cases
      during the year 2008, this ratio decreased by 40.9% after the establishment of
      the animal shelter in the year 2009. During the year 2010, where we had the
      highest number of homeless dog collection to the animal shelter, the decrease in
      suspected rabies bites reached the maximum decrease, namely 51.0%. Spearman
      correlation analysis showed a strong negative correlation between the number of
      collected animals and suspected rabies bites (r = -0,862; p=0.006). CONCLUSION:
      Suspected rabies cases are common in Turkey and some cases of rabies are
      encountered. The number of suspected rabies bites in Erzurum has decreased
      significantly after establishing the animal shelter. It is an evident that
      establishing rehabilitation centers for homeless animals in all cities will have
      an important role in controlling zoonotic diseases including rabies.

PMID- 25610318
TI  - Metabolic syndrome in school children in mardin, South-eastern of Turkey.
AB  - OBJECTIVE: To determine the prevalence of the metabolic syndrome (MES) in a
      school children population. MATERIALS AND METHODS: Three thousand four hundred
      and sixty children aged between 7 and 15 in three elementary schools in the city
      of Mardin, located in the south-eastern region of Turkey, were included in this
      study in April and May 2011. Age, gender, height, weight, waist circumference
      (WC), hip circumference, waist/hip ratio, systolic and diastolic blood pressure
      were measured and a variety of blood tests were done. The International Diabetes
      Federation (IDF) criteria were used for the diagnosis of MES. RESULTS: It was
      found that 9.42% of those tested were overweight, and 8.0% were obese. The study
      found that more girls (9.1%) were obese than girls (6.9%). The prevalence of
      obesity was significantly higher among girls than boys (p<0.001). A positive
      correlation was found between body mass index (BMI) and the other parameters,
      namely waist and hip circumference, waist/hip ratio, systolic and diastolic blood
      pressure (BP), triglyceride (TG) (p=0.0001). It was found that total cholesterol
      (T-Chol), TG, BMI, systolic and diastolic BP were significantly different among
      obese MES's group and non-obese children (p<0.05). The waist/hip ratio reference
      value in girls was significantly higher than boys (p>0.05). The prevalence of MES
      was 6.3%. The number of components of MES was higher in girls and obese children.
      The rate of MES was 30.3% in obese children. CONCLUSION: The frequency of
      obesity, hypertension and MES in childhood period have been steadily increasing.
      Children who are classified having central obesity and high body mass index
      should be more carefully evaluated to its potential to progress to MES. And the
      quality of the life should be improved by reducing the risks resulted from life
      style changes, necessary treatments and follow ups.

PMID- 25610319
TI  - Relation of Preoperative Thrombocytosis between Tumor Stage and Grade in Patients
      with Endometrial Cancer.
AB  - OBJECTIVE: We aimed to evaluate the predictive value of preoperative
      thrombocytosis for postoperative tumor stage and tumor grade in patients with
      endometrial cancer. MATERIALS AND METHODS: This was a retrospective study carried
      out in our gynecologic oncology department between January 2000 and December
      2011. We reviewed the medical charts of 190 patients diagnosed with endometrial
      carcinoma and underwent complete staging procedure. The clinicopathologic
      characteristics of the patients such as; age, gravidity, parity, menopausal
      status, body mass index, co-morbidities (diabetes, hypertension etc.), stage,
      grade, histological subtype, depth of myometrial invasion, peritoneal washing
      cytology and preoperative platelet count were recorded. Endometrioid
      adenocarcinomas were graded according to the FIGO classification. Blood samples
      for the measurement of platelet count were obtained 3 days prior to the surgery.
      Thrombocytosis was defined as a platelet count of 300*10(9)/L. P values less than
      0.05 derived from two-tailed tests were considered statistically significant.
      RESULTS: The mean age of the study population was 55.4 (range 33-80) years. The
      mean gravidity was 3.8 (range 0-12) and the mean parity was 3.32 (range 0-11).
      108 (56,8%) patients were with body mass index of >30 kg/m(2). The mean platelet
      count among women was 288, 6+/-90.7*10(9)/L (range 105-772*10(9)/L). The majority
      of the patients were with early stage diseases during the surgeries. 170 (89.5%)
      of the patients had stage I to II disease, and 20 (10.5%) of them had stage III
      to IV disease. There were no statistical significance between thrombocytosis and
      age, gravidity, parity, BMI, cancer grade and stage, histological subtype of the
      tumor, depth of invasion, cervical involvement, intrauterine tumor volume and
      peritoneal washing cytology. CONCLUSION: We found that preoperative platelet
      count was not correlated with the stage or grade of endometrial cancer.

PMID- 25610320
TI  - Body composition in patients with stable chronic obstructive pulmonary disease:
      comparison with malnutrition in healthy smokers.
AB  - OBJECTIVE: Although malnutrition (body mass index (BMI)<18.5kg/ m(2)) has been
      associated with impaired health status in patients with chronic obstructive
      pulmonary disease (COPD), the effects of body composition (body fat and protein
      percentage) in patients with COPD have not been clearly demonstrated. MATERIALS
      AND METHODS: A total of 180 stable patients with COPD at the stages of moderate,
      severe, very severe, and 50 healthy subjects were included in this prospective
      study. All subjects underwent a clinical evaluation, spirometry tests,
      anthropometric measurements and blood analysis. RESULTS: Frequency of underweight
      was higher in COPD (11.7%) patients than the control group (8%). The frequency of
      underweight increased as the severity of COPD worsens. There was body
      decomposition (protein or fat depletion) in not only all underweight patients but
      also some normal/overweight COPD patients, as well as in the healthy subjects.
      Deterioration in FEV1 (L), and FEV1/FVC was more evident in underweight patients
      with protein and fat depletion compared to normal/overweight patients (p=0.004,
      and p=0.005). Inspiratory and expiratory respiratory muscle power was lower in
      under-weight patients with depletion than in normal/overweight patients (p=0.02,
      and p=0.01). DLCO and DLCO/VA were significantly lower in underweight patients
      than in normal/overweight patients (p=0.003, and p=0.004), they were also lower
      in normal/overweight patients with depletion than in normal/overweight patients
      with no depletion (p=0.01, and p=0.07). Normal/overweight patients with protein
      depletion had the most frequent number of exacerbations than others (p=0.04).
      CONCLUSION: These results show that the body decomposition is important in
      patients with COPD. Assessment of body composition should be a part of
      nutritional assessment besides BMI in patients with COPD.

PMID- 25610321
TI  - Association between Hepatocyte Growth Factor (HGF) Gene Polymorphisms and Serum
      HGF Levels in Patients with Rheumatoid Arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease
      characterized by proliferation and insufficient apoptosis of synovial cell,
      inflammatory cell infiltration, angiogenesis, and destruction of joints.
      Hepatocyte growth factor (HGF) has many functions, such as regulation of
      inflammation, angiogenesis, and inhibition of apoptosis. The purpose of this
      study was to investigate the association between intron 13 C/A and intron 14 T/C
      HGF gene polymorphisms and serum HGF levels in patients with RA. MATERIALS AND
      METHODS: 100 patients with RA and 123 healthy controls were included in this
      study. Serum HGF concentrations were measured using ELISA kit. Gene polymorphisms
      were determined by allelic discrimination analysis using the real-time PCR
      method. RESULTS: HGF levels, frequency of AA genotype and A allele for intron 13
      C/A polymorphism and frequency of CC genotype and C allele for intron 14 T/C
      polymorphism were increased in patients with RA compared to healthy controls.
      There was no overall associations between genotypes and serum HGF concentrations
      in both patient and control groups. CONCLUSION: Our results indicate that HGF
      protein and gene may play an important role in the etiopathogenesis of RA.
      However, further studies are required for a better understanding of mechanisms
      related to the disease process.

PMID- 25610322
TI  - The Effects of Metabolic Syndrome on TpTe Interval and TpTe/QT Ratio in Patients
      with Normal Coronary Arteries.
AB  - OBJECTIVE: T wave peak to T wave end (TpTe) interval and TpTe/QT have been
      accepted as predictors of ventricular arrythmia. In this study our aim is to
      investigate the effect of metabolic syndome on these parameters in patients with
      angiographically normal coronary arteries. MATERIALS AND METHODS: Thirty patients
      with metabolic syndrome (4 male, mean age 52+/-7.8 years) and twenty patients
      without metabolic syndrome as control group (8 male, mean age 54+/-9.3 years)
      were included. TpTe interval and TpTe/QT ratio were measured from the 12-lead
      electrocardiogram. These parameters were compared between the groups. RESULTS:
      When compared with to the control group the systolic and diastolic blood
      pressure, pulse pressure, waist circumference, triglyceride and fasting plasma
      glucose levels were higher and HDL cholesterol level was lower in the metabolic
      syndrome group. In the analysis of electrocardiography, QT dispersion (QTd) and
      corrected QTd were significantly increased in metabolic syndrome group as
      compared to the controls group (44+/-14 versus 30+/-12 ms and 433+/-10 versus
      405+/-4 ms, all p value p=0.01). TpTe interval and TpTe/QT ratio were also
      significantly higher in patient with metabolic syndrome (112+/-10 versus 91+/-10
      ms and 0.25+/-0.02 versus 0.22+/-0.01, all p value p=0.01). CONCLUSION: According
      to these results, we supposed that TpTe/QT ratio and TpTe interval is prolonged
      and those patients with metabolic syndrome may be at greater risk of ventricular
      arrhythmias.

PMID- 25610323
TI  - Trace elements in children suffering from idiopathic nephrotic syndrome.
AB  - OBJECTIVE: Trace elements play a significant role in several metabolic processes
      and often circulate in the blood binding to protein. The purpose of this study
      was to determine the status of selenium, zinc, and boron in idiopathic nephrotic
      syndrome patients in active and remission phases. MATERIALS AND METHODS: Fourteen
      patients and fourteen healthy age-matched controls were included in the study.
      The selenium, zinc and boron level in plasma and urine were measured by the
      inductively coupled plasma mass spectrometry. RESULTS: The plasma levels of zinc
      and selenium were significantly lower in both active and remission patients (for
      all p=0.0001). The plasma boron level was significantly lower only in patients in
      active phase (p=0.0002 vs control). The concentrations of urinary boron and
      selenium were significantly higher during active phase compared with remission
      (p=0.0003 and 0.0001, respectively). CONCLUSION: Supplementation with zinc,
      selenium and boron may be justified in patients suffering with this disease.

PMID- 25610324
TI  - Are new generations getting bigger in size? Anthropometric measurements in
      erzurum.
AB  - OBJECTIVE: When the dimensional measurements of the students who spend most of
      their time at school are taken into consideration, inappropriate dimensions of
      school equipment may affect their body and psychological improvements negatively.
      Anthropometric measurements are necessary for designing the educational equipment
      of the children at school. It is emphasized that anthropometric measurements of
      the people living in different climate and altitude conditions will be different.
      It is mentioned that anthropometric data available for a certain region will be
      able to change as a result of changing socio-economical conditions and therefore,
      anthropometric data update is necessary at certain periods. MATERIALS AND
      METHODS: In 2000 anthropometric data obtained from the children between the age
      of seven and fifteen, who were in sitting and standing positions, were measured
      with a repeated measurement in the same schools in 2007. RESULTS: Mean values of
      the heights of elbow at standing position of the female students, 8 years old,
      increased from 72.38 cm in 2000 to 74.67 cm in 2007 (p<0.001). Most of the other
      measurements in 2007 were larger than those in 2000, giving the impression that
      new generation children are getting larger in size. CONCLUSION: As reported in
      the literature, anthropometric data should be updated at certain period of times.

PMID- 25610325
TI  - Impaired visibility of the hepatic veins on the multi-detector computed
      tomography in patients with cirrhosis.
AB  - OBJECTIVE: To determine the prevalence and associations of the impaired
      visibility of the hepatic veins (HV) on the multi-detector row computed
      tomography (MDCT) in cirrhotic patients. MATERIALS AND METHODS: Eighty-seven
      consecutive cirrhotic patients undergoing triphasic liver MDCT were enrolled. The
      patency of the HV and the direction of the blood flow in the main portal vein,
      inhomogeneity of the liver, portal vein thrombosis (PVT), a spontaneous
      splenorenal shunt, splenic indexes (cm(3)), contour abnormalities, and
      enlargement of the fissure were evaluated. RESULTS: The prevalence of the
      impaired visibility of the HV was 38% in the patients with cirrhosis. No
      significant associations exist between the impaired visibility of the HV and age
      (p=0.96), sex (p=0.14), portal vein thrombosis (p=0.29), or splenic indexes
      (p=0.32). Inhomogeneity of the liver (p=0.0001), marked contour abnormalities,
      (p=0.0001), splenorenal shunt (p=0.02), enlargement of fissure (p=0.0001), and
      hepatofugal flow (p=0.01) were significantly associated with the impaired
      visibility of the HV. CONCLUSION: Inhomogeneity of the liver, marked contour
      abnormalities, and hepatofugal flow are independently associated with the
      impaired visibility of the HV in cirrhotic patients on hepatic venous phase CT.

PMID- 25610326
TI  - Household Cooking Fuel Use among Residents of a Sub-Urban Community in Nigeria:
      Implications for Indoor Air Pollution.
AB  - OBJECTIVE: The aim of this study is to assess the types of household cooking fuel
      used by residents of Isiohor community in Edo State, Nigeria. MATERIALS AND
      METHODS: This descriptive cross-sectional study was conducted among 133 household
      heads or their representatives in Isiohor Community in Edo State, Nigeria. Data
      collection was by means of a structured interviewer administered questionnaire.
      RESULTS: Half (50.3%) of the households studied were made up of 4-6 persons
      living in them. Sixty-two (46.6%) respondents had tertiary level of education and
      a third 44 (33.1%) earned between 21,000 and 30,000 naira (150-200 dollars)
      monthly. Forty six (34.6%) and 27 (20.3%) respondents live in passage houses and
      flats respectively. Two thirds (68.4%) of the respondents cook their food
      indoors. The predominant household cooking fuels used by the respondents were
      cooking gas (51.1%), Kerosene (45.9%), vegetables (25.6%) and firewood (14.3%).
      Majority 106 (79.7%) had poor knowledge of the health effects of prolonged
      exposure to smoke arising from indoor cooking. There was a statistically
      significant association between the occupation of the respondents and the type of
      household cooking fuel used (p=0.002). CONCLUSION: The use of unclean indoor
      cooking fuel was high among the residents of Isiohor community in Edo State,
      Nigeria. Also, there was poor knowledge of the health effects of prolonged
      exposure to smoke from unclean cooking fuel among the respondents and this has
      serious implications for indoor air pollution. There is an urgent need for
      health/hygiene education on the health effects of use of unclean indoor cooking
      fuel among these residents. There is also need for use of clean/green cooking
      stoves and construction of exhaust ventilation pipes in these households.

PMID- 25610327
TI  - Management of tracheobronchial injuries.
AB  - Tracheobronchial injury is one of cases which are relatively uncommon, but must
      be suspected to make the diagnosis and managed immediately. In such a case,
      primary initial goals are to stabilize the airway and localize the injury and
      then determine its extend. These can be possible mostly with flexible
      bronchoscopy conducted by a surgeon who can repair the injury. Most of the
      penetrating injuries occur in the cervical region. On the other hand, most of the
      blunt injuries occur in the distal trachea and right main bronchus and they can
      be best approached by right posterolateral thoracotomy. The selection of the
      manner and time of approaching depends on the existence and severity of
      additional injuries. Most of the injuries can be restored by deploying simple
      techniques such as individual sutures, while some of them requires complex
      reconstruction techniques. Apart from paying attention to the pulmonary toilet,
      follow-up is crucial for determination of anastomotic technique or stenosis.
      Conservative treatment may be considered an option with a high probability of
      success in patients meeting the criteria, especially in patients with iatrogenic
      tracheobronchial injury. 

PMID- 25610328
TI  - Ectopic thyroid tissue in submandibular and infrahyoid region.
AB  - The thyroid is the first endocrine gland to form during embryogenesis. At this
      stage, incomplete or anomalous migration of thyroid tissue causes ectopic
      localization of the gland. Submandibular ectopic thyroid tissue with a coexisting
      normally located thyroid gland is extremely rare. In this case aimed to present
      the findings of the 65-years-old female patient who is bilateral subtotal
      thyroidectomy operation performed for multinodular goiter of 12 years ago. Case,
      painless mass in the right submandibular and infrahyoid region for 6 months was
      admitted to our clinic with complaints. Result of contrast-enhanced neck computed
      tomography, ultrasound-guided fine-needle aspiration biopsy and thyroid
      scintigraphy were found of functional residual thyroid tissue in the normal
      localization as well as 2*3 cm mass in the submandibular area and 1*2 cm mass
      lesion in the infrahyoid region. The patient referred to excisional biopsy.
      Normal thyroid follicules and no evidence of malignancy were found in specimen
      pathologically. Postoperative follow-up of thyroid function tests were normal. 

PMID- 25610329
TI  - Chromosomal Translocation t (10;19) (q11.2;q13.4) in an Infertile Male.
AB  - Chromosomal rearrangements are usually associated with male factor infertility.
      We report here a 34-year-old man suffering from primary infertility for 15 years.
      The cytogenetic analysis and investigation of Y-chromosome microdeletions were
      performed. A reciprocal balanced translocation t (10;19) (q11.2;q13.4) was found
      in oligozoospermic infertile men with no Y-chromosome microdeletions. In this
      case, we aimed to evaluate the 46,XY,t (10;19) (q11.2;q13.4) karyo-type, which
      was detected through a cytogenetic analysis of a person referred to our genetic
      laboratory due to primary infertility, in the light of the literature. 

PMID- 25610330
TI  - Obturator hernia, a rare cause of small bowel obstruction: case report.
AB  - Obturator hernia is a rare hernia in the world, diagnosed late since it has no
      specific symptoms and findings and generally occur in thin and old women with
      comorbidity.For this reason obturator hernia has high morbidity and mortality
      rates. In this study, we present an obturator hernia case that Howship-Romberg
      sign is positive and has typical appearance in computerized tomography.
      Laparotomy was performed on 89 years old female patient with body mass index
      18.08 kg/m(2) by low middle line incision. Following the segmentectomy to the
      strangulated small bowel loop, obturator canal is repaired by retroperitoneal
      application. No complication occurred in the postoperative period. Obturator
      hernia should be taken into consideration in old and thin female patients with
      intestinal obstruction. Computerized tomography should be performed for early
      diagnosis of the obturator hernia. 

PMID- 25610331
TI  - 'Lichtenberg figure' as a result of lightning shock.

PMID- 25610332
TI  - Systematic status of true katydids Sathrophyllia (Orthoptera, Tettigonioidea,
      Pseudophyllinae) from Pakistan, with description of two new species.
AB  - The genus Sathrophyllia Stal, 1874 from Pakistan is reviewed with four species
      recorded. The diagnostic characters are given and two new species
      Sathrophylliasaeedi sp. n. and Sathrophylliairshadi sp. n. are described. In
      addition to that Sathrophyllianr.rugosa (Linnaeus, 1758) and
      Sathrophylliafemorata (Fabricius, 1787) are re-described. Further information on
      the distribution and ecology of the species is given and a key to studied species
      of Sathrophyllia is presented. Sathrophylliafemorata (Fabricius, 1787) and
      Sathrophylliarugosa (Linnaeus, 1758) are recorded from Rawalakot (KPK) and
      Tharparker (Sindh), Pakistan for first the time. 

PMID- 25610333
TI  - Contribution to the knowledge of seed-beetles (Coleoptera, Chrysomelidae,
      Bruchinae) in Xinjiang, China.
AB  - Nineteen species of seed-beetles belonging to the subfamily Bruchinae
      (Coleoptera, Chrysomelidae) were collected in Xinjiang, China. Of these, the
      following four were new records for China: Bruchusaffinis Frolich, 1799,
      Bruchusatomarius L., 1761, Bruchusloti Paykull, 1800 and Kytorhinuskergoati
      Delobel & Legalov, 2009. We provide an annotated checklist, illustrations and a
      key to the 19 species. 

PMID- 25610334
TI  - The new genus Pheude (Coleoptera, Curculionidae, Cossoninae) with description of
      a new species from mainland China.
AB  - A new weevil, Pheudepunctatus gen. et sp. n., of the tribe Dryotribini in
      Cossoninae, is described from Guangdong Province, South China. It differs from
      the related genera Dryotribus Horn and Microtribodes Morimoto in having antennae
      with seven articles and a distinct scutellum, and from Ochronanus Pascoe and
      Stenomimus Wollaston in having long antennae, a rostrum with a medio-longitudinal
      furrow beginning at the posterior margin of the eyes and extending approximately
      midway on the rostrum, and a moderately elevated, medio-longitudinal carina
      extending the full length of the pronotum. Other diagnostic characters and
      illustrations are provided. A key to the genera of Dryotribini known from China
      is given. 

PMID- 25610335
TI  - A new parasitoid of Bazariaturensis (Lepidoptera, Pyralidae): Campoplexbazariae
      sp. n. (Hymenoptera, Ichneumonidae).
AB  - A new solitary endoparasitoid of the larva of Bazariaturensis Ragonot, 1887
      (Lepidoptera, Pyralidae) in Qinghai province, China, Campoplexbazariae Sheng, sp.
      n., belonging to the subfamily Campopleginae (Hymenoptera, Ichneumonidae), is
      reported. Illustrations of the new species are provided. 

PMID- 25610336
TI  - A taxonomic study of the genus Panesthia (Blattodea, Blaberidae, Panesthiinae)
      from China with descriptions of one new species, one new subspecies and the male
      of Panesthiaantennata.
AB  - One new species Panesthiaguizhouensis sp. n. and one new subspecies
      Panesthiastellataconcava ssp. n. are described and illustrated. The male of
      Panesthiaantennata Brunner von Wattenwyl, 1893 and its brachypterous form are
      described and illustrated for the first time. Panesthiastrelkovi Bey-Bienko, 1969
      is redescribed and illustrated. Three known species, Panesthiabirmanica Brunner
      von Wattenwyl, 1893, Panesthiasinuata Saussure, 1839 and
      Panesthiaangustipenniscognata Bey-Bienko, 1969 are illustrated. In addition, a
      key to all species of the genus Panesthia from China is presented. 

PMID- 25610337
TI  - Four new species of hangingflies (Insecta, Mecoptera, Bittacidae) from the Middle
      Jurassic of northeastern China.
AB  - Two new species of Mongolbittacus Petrulevicius, Huang & Ren, 2007,
      Mongolbittacusspeciosus sp. n. and Mongolbittacusoligophlebius sp. n., and two
      new species of Exilibittacus Yang, Ren & Shih, 2012, Exilibittacusfoliaceus sp.
      n. and Exilibittacusplagioneurus sp. n., in the family Bittacidae, are described
      and illustrated based on five well-preserved fossil specimens. These specimens
      were collected from the late Middle Jurassic Jiulongshan Formation of Daohugou,
      Inner Mongolia, China. These new findings enhance our understanding of the
      morphological characters of early hangingflies and highlight the diversity of
      bittacids in the Mid Mesozoic ecosystems. 

PMID- 25610338
TI  - A new species of the leafhopper genus Calodia Nielson, 1982 (Hemiptera,
      Cicadellidae, Coelidiinae) from China, with a key to Chinese species.

PMID- 25610339
TI  - A Dataset of Deep-Sea Fishes Surveyed by Research Vessels in the Waters around
      Taiwan.
AB  - The study of deep-sea fish fauna is hampered by a lack of data due to the
      difficulty and high cost incurred in its surveys and collections. Taiwan is
      situated along the edge of the Eurasia fig, at the junction of three Large Marine
      Ecosystems or Ecoregions of the East China Sea, South China Sea and the
      Philippines. As nearly two-thirds of its surrounding marine ecosystems are deep
      sea environments, Taiwan is expected to hold a rich diversity of deep-sea fish.
      However, in the past, no research vessels were employed to collect fish data on
      site. Only specimens, caught by bottom trawl fishing in the waters hundreds of
      meters deep and missing precise locality information, were collected from Dasi
      and Donggang fishing harbors. Began in 2001, with the support of National Science
      Council, research vessels were made available to take on the task of
      systematically collecting deep-sea fish specimens and occurrence records in the
      waters surrounding Taiwan. By the end of 2006, a total of 3,653 specimens,
      belonging to 26 orders, 88 families, 198 genera and 366 species, were collected
      in addition to data such as sampling site geographical coordinates and water
      depth, and fish body length and weight. The information, all accessible from the
      "Database of Taiwan's Deep-Sea Fauna and Its Distribution
      (http://deepsea.biodiv.tw/)" as part of the "Fish Database of Taiwan," can
      benefit the study of temporal and spatial changes in distribution and abundance
      of fish fauna in the context of global deep-sea biodiversity. 

PMID- 25610340
TI  - Ninety-eight new species of Trigonopterus weevils from Sundaland and the Lesser
      Sunda Islands.
AB  - The genus Trigonopterus Fauvel, 1862 is highly diverse in Melanesia. Only one
      species, Trigonopterusamphoralis Marshall, 1925 was so far recorded West of
      Wallace's Line (Eastern Sumatra). Based on focused field-work the fauna from
      Sundaland (Sumatra, Java, Bali, Palawan) and the Lesser Sunda Islands (Lombok,
      Sumbawa, Flores) is here revised. We redescribe Trigonopterusamphoralis Marshall
      and describe an additional 98 new species: Trigonopterusacuminatus sp. n.,
      Trigonopterusaeneomicans sp. n., Trigonopterusalaspurwensis sp. n.,
      Trigonopterusallopatricus sp. n., Trigonopterusallotopus sp. n.,
      Trigonopterusangulicollis sp. n., Trigonopterusargopurensis sp. n.,
      Trigonopterusarjunensis sp. n., Trigonopterusasper sp. n.,
      Trigonopterusattenboroughi sp. n., Trigonopterusbaliensis sp. n.,
      Trigonopterusbatukarensis sp. n., Trigonopterusbawangensis sp. n.,
      Trigonopterusbinodulus sp. n., Trigonopterusbornensis sp. n., Trigonopteruscahyoi
      sp. n., Trigonopteruscostipennis sp. n., Trigonopteruscuprescens sp. n.,
      Trigonopteruscupreus sp. n., Trigonopterusdacrycarpi sp. n., Trigonopterusdelapan
      sp. n., Trigonopterusdentipes sp. n., Trigonopterusdiengensis sp. n.,
      Trigonopterusdimorphus sp. n., Trigonopterusdisruptus sp. n., Trigonopterusdua
      sp. n., Trigonopterusduabelas sp. n., Trigonopterusechinatus sp. n.,
      Trigonopterusempat sp. n., Trigonopterusenam sp. n., Trigonopterusfissitarsis sp.
      n., Trigonopterusflorensis sp. n., Trigonopterusfoveatus sp. n.,
      Trigonopterusfulgidus sp. n., Trigonopterusgedensis sp. n.,
      Trigonopterushalimunensis sp. n., Trigonopterushonjensis sp. n.,
      Trigonopterusijensis sp. n., Trigonopterusjavensis sp. n.,
      Trigonopteruskalimantanensis sp. n., Trigonopteruskintamanensis sp. n.,
      Trigonopterusklatakanensis sp. n., Trigonopteruslampungensis sp. n.,
      Trigonopteruslatipes sp. n., Trigonopteruslima sp. n., Trigonopteruslombokensis
      sp. n., Trigonopterusmerubetirensis sp. n., Trigonopterusmesehensis sp. n.,
      Trigonopterusmicans sp. n., Trigonopterusmisellus sp. n.,
      Trigonopteruspalawanensis sp. n., Trigonopteruspangandaranensis sp. n.,
      Trigonopterusparaflorensis sp. n., Trigonopteruspararugosus sp. n.,
      Trigonopterusparasumbawensis sp. n., Trigonopteruspauxillus sp. n.,
      Trigonopteruspayungensis sp. n., Trigonopterusporcatus sp. n.,
      Trigonopteruspseudoflorensis sp. n., Trigonopteruspseudosumbawensis sp. n.,
      Trigonopteruspunctatoseriatus sp. n., Trigonopterusranakensis sp. n.,
      Trigonopterusrelictus sp. n., Trigonopterusrinjaniensis sp. n.,
      Trigonopterusroensis sp. n., Trigonopterusrugosostriatus sp. n.,
      Trigonopterusrugosus sp. n., Trigonopterusrutengensis sp. n.,
      Trigonopterussaltator sp. n., Trigonopterussantubongensis sp. n.,
      Trigonopterussasak sp. n., Trigonopterussatu sp. n., Trigonopterusschulzi sp. n.,
      Trigonopterussebelas sp. n., Trigonopterussembilan sp. n., Trigonopterussepuluh
      sp. n., Trigonopterusseriatus sp. n., Trigonopterusserratifemur sp. n.,
      Trigonopterussetifer sp. n., Trigonopterussilvestris sp. n.,
      Trigonopterussingkawangensis sp. n., Trigonopterussingularis sp. n.,
      Trigonopterussinuatus sp. n., Trigonopterussqualidus sp. n.,
      Trigonopterussumatrensis sp. n., Trigonopterussumbawensis sp. n.,
      Trigonopterussundaicus sp. n., Trigonopterussuturalis sp. n.,
      Trigonopterussyarbis sp. n., Trigonopterustelagensis sp. n.,
      Trigonopterustepalensis sp. n., Trigonopterustiga sp. n.,
      Trigonopterustrigonopterus sp. n., Trigonopterustujuh sp. n.,
      Trigonopterusujungkulonensis sp. n., Trigonopterusvariolosus sp. n.,
      Trigonopterusvulcanicus sp. n., Trigonopteruswallacei sp. n.. All new species are
      authored by the taxonomist-in-charge, Alexander Riedel. Most species belong to
      the litter fauna of primary wet evergreen forests. This habitat has become highly
      fragmented in the study area and many of its remnants harbor endemic species.
      Conservation measures should be intensified, especially in smaller and less
      famous sites to minimize the number of species threatened by extinction. 

PMID- 25610341
TI  - Description of 23 new species of the Exocelinaekari-group from New Guinea, with a
      key to all representatives of the species group (Coleoptera, Dytiscidae,
      Copelatinae).
AB  - Twenty three new species of Exocelina Broun, 1886 from New Guinea are described
      herein: Exocelinabewaniensis sp. n., Exocelinabismarckensis sp. n.,
      Exocelinacraterensis sp. n., Exocelinagorokaensis sp. n., Exocelinaherowana sp.
      n., Exocelinajimiensis sp. n., Exocelinakisli sp. n., Exocelinaksionseki sp. n.,
      Exocelinalembena sp. n., Exocelinamantembu sp. n., Exocelinamichaelensis sp. n.,
      Exocelinapinocchio sp. n., Exocelinapseudoastrophallus sp. n.,
      Exocelinapseudobifida sp. n., Exocelinapseudoedeltraudae sp. n.,
      Exocelinapseudoeme sp. n., Exocelinasandaunensis sp. n., Exocelinasimbaiarea sp.
      n., Exocelinaskalei sp. n., Exocelinatabubilensis sp. n., Exocelinatariensis sp.
      n., Exocelinavovai sp. n., and Exocelinawannangensis sp. n. All of them have been
      found to belong to the Exocelinaekari-group. An identification key to all known
      species of the group is provided, and important diagnostic characters (habitus,
      color, male antennae, protarsomeres 4-5, median lobes, and parameres) are
      illustrated. Data on the distribution of the new species and some already
      described species are given. 

PMID- 25610342
TI  - A new Heraclides swallowtail (Lepidoptera, Papilionidae) from North America is
      recognized by the pattern on its neck.
AB  - Heraclidesrumiko Shiraiwa & Grishin, sp. n. is described from southwestern United
      States, Mexico, and Central America (type locality: USA, Texas, Duval County). It
      is closely allied to Heraclidescresphontes (Cramer, 1777) and the two species are
      sympatric in central Texas. The new species is diagnosed by male genitalia and
      exhibits a nearly 3% difference from Heraclidescresphontes in the COI DNA barcode
      sequence of mitochondrial DNA. The two Heraclides species can usually be told
      apart by the shape and size of yellow spots on the neck, by the wing shape, and
      the details of wing patterns. "Western Giant Swallowtail" is proposed as the
      English name for Heraclidesrumiko. To stabilize nomenclature, neotype for
      Papiliocresphontes Cramer, 1777, an eastern United States species, is designated
      from Brooklyn, New York, USA; and lectotype for Papiliothoas Linnaeus, 1771 is
      designated from Suriname. We sequenced DNA barcodes and ID tags of nearly 400
      Papilionini specimens completing coverage of all Heraclides species. Comparative
      analyses of DNA barcodes, genitalia, and facies suggest that Heraclidesoviedo
      (Gundlach, 1866), reinstated status, is a species-level taxon rather than a
      subspecies of Heraclidesthoas (Linnaeus, 1771); and Heraclidespallas (G. Gray,
      [1853]), reinstated status, with its subspecies HeraclidesPapiliobajaensis (J.
      Brown & Faulkner, 1992), comb. n., and Heraclidesanchicayaensis Constantino, Le
      Crom & Salazar, 2002, stat. n., are not conspecific with Heraclidesastyalus
      (Godart, 1819). 

PMID- 25610343
TI  - Island life in the Cretaceous - faunal composition, biogeography, evolution, and
      extinction of land-living vertebrates on the Late Cretaceous European
      archipelago.
AB  - The Late Cretaceous was a time of tremendous global change, as the final stages
      of the Age of Dinosaurs were shaped by climate and sea level fluctuations and
      witness to marked paleogeographic and faunal changes, before the end-Cretaceous
      bolide impact. The terrestrial fossil record of Late Cretaceous Europe is
      becoming increasingly better understood, based largely on intensive fieldwork
      over the past two decades, promising new insights into latest Cretaceous faunal
      evolution. We review the terrestrial Late Cretaceous record from Europe and
      discuss its importance for understanding the paleogeography, ecology, evolution,
      and extinction of land-dwelling vertebrates. We review the major Late Cretaceous
      faunas from Austria, Hungary, France, Spain, Portugal, and Romania, as well as
      more fragmentary records from elsewhere in Europe. We discuss the paleogeographic
      background and history of assembly of these faunas, and argue that they are
      comprised of an endemic 'core' supplemented with various immigration waves. These
      faunas lived on an island archipelago, and we describe how this insular setting
      led to ecological peculiarities such as low diversity, a preponderance of
      primitive taxa, and marked changes in morphology (particularly body size
      dwarfing). We conclude by discussing the importance of the European record in
      understanding the end-Cretaceous extinction and show that there is no clear
      evidence that dinosaurs or other groups were undergoing long-term declines in
      Europe prior to the bolide impact. 

PMID- 25610344
TI  - Assessment of objective ambulation in lower extremity sarcoma patients with a
      continuous activity monitor: rationale and validation.
AB  - In addition to patient reported outcome measures, accelerometers may provide
      useful information on the outcome of sarcoma patients treated with limb salvage.
      The StepWatch (SW) Activity Monitor (SAM) is a two-dimensional accelerometer worn
      on the ankle that records an objective measure of walking performance. The
      purpose of this study was to validate the SW in a cross-sectional population of
      adult patients with lower extremity sarcoma treated with limb salvage. The main
      outcome was correlation of total steps with the Toronto Extremity Salvage Score
      (TESS). In a sample of 29 patients, a mean of 12 days of SW data was collected
      per patient (range 6-16), with 2767 average total steps (S.D. 1867; range 406
      7437). There was a moderate positive correlation between total steps and TESS (r
      = 0.56,  P = 0.002). Patients with osseous tumors walked significantly less than
      those with soft tissue sarcoma (1882 versus 3715, P < 0.01). This study supports
      the validity of the SAM as an activity monitor for the objective assessment of
      real world physical function in sarcoma patients. 

PMID- 25610345
TI  - Rasburicase in the management of tumor lysis: an evidence-based review of its
      place in therapy.
AB  - Tumor lysis syndrome (TLS) is a potentially life-threatening complication of
      cancer therapy characterized by two or more of the following laboratory
      abnormalities: hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia,
      with resultant end-organ damage, eg, renal failure, seizures, or cardiac
      arrhythmias. High-risk patients include those with highly proliferative cancers
      and/or large tumor burdens, particularly in the setting of highly effective
      chemotherapy, among other risk factors. Before 2002, antihyperuricemic drug
      therapy was limited to allopurinol, a xanthine oxidase inhibitor. Rasburicase, a
      recombinant urate oxidase, was approved by the US Food and Drug Administration
      for children in 2002 and adults in 2009, ushering in a new era in TLS therapy. We
      attempted to critically appraise the available evidence supporting the perceived
      benefits of rasburicase in the management of TLS. A Medline search yielded 98
      relevant articles, including 26 retrospective and 22 prospective studies of
      rasburicase for the treatment of TLS, which were then evaluated to determine the
      best available evidence for the effectiveness of rasburicase in terms of disease
      oriented, patient-oriented, and economic outcomes. Rasburicase is now a standard
      of care for patients at high risk of TLS despite continuing debate on the
      correlation between its profound and rapid lowering of plasma uric acid levels
      with hard patient outcomes, eg, need for renal replacement therapy and mortality.
      Rasburicase is dramatically effective in lowering plasma uric acid levels. The
      mortality and cost-effectiveness benefits of this expensive drug remain to be
      conclusively proven, and well designed, randomized controlled trials are needed
      to answer these fundamentally important questions. 

PMID- 25610346
TI  - Antioxidant enzyme inhibitor role of phosphine metal complexes in lung and
      leukemia cell lines.
AB  - Phosphine metal complexes have been recently evaluated in the field of cancer
      therapy. In this research, the cytotoxic effects of some metal phosphines
      {[PdCl2((CH2OH)2PCH2)2NCH3] (C1), [RuCl2(((CH2OH)2PCH2)2NCH3)2] (C2),
      [PtCl2((Ph2PCH2)2NCH3)(timin)2] (C3)} on K562 (human myelogenous leukemia cell
      line) and A549 (adenocarcinomic human alveolar basal epithelial cells) cells were
      investigated using the MTT test. C1 and C2 are water-soluble metal complexes,
      which may have some advantages in in vitro and in vivo studies. The effects of
      the above-mentioned metal complexes on thioredoxin reductase (TrxR) (EC:
      1.8.1.9), glutathione peroxidase (GPx) (EC: 1.11.1.9), and catalase (Cat) (EC:
      1.11.1.6) enzymes were also tested. The results of this research showed that all
      three metal complexes indicated dose-dependent cytotoxicity on A549 and K562 cell
      lines and that the complexes inhibited different percentages of the TrxR, GPx,
      and Cat enzymes of these tumor cells. 

PMID- 25610347
TI  - Oral premalignant lesions: epidemiological and clinical analysis in the northern
      Polish population.
AB  - INTRODUCTION: Leukoplakia is the most common potentially malignant condition of
      the oral cavity. AIM: Epidemiological and clinical analysis of patients with oral
      leukoplakia (OL) diagnosed and treated in the Department of Maxillofacial and
      Oral Surgery, Medical University of Gdansk. MATERIAL AND METHODS: The study was
      retrospective and prospective. Among 55 911 patients diagnosed and treated in the
      Department in 1999-2009, 204 people with OL were selected. The material includes
      104 women and 100 men with an average age of 58.1. Most of the patients were in
      the age group of 50-70 years, average age was 58.1. RESULTS: The most common
      concomitant disease was diabetes. More than 88% of the patients declared
      occurrence of OL predisposing development factors (50.49% - cigarette smoking).
      Three hundred and twenty foci of OL were found among patients. Homogeneous OL
      dominated (72.05%). Multifocal OL was diagnosed in 58.3% of patients. The most
      common location of lesions was buccal mucosa (52.2%). Cancers developed on the
      basis of OL in 7 patients (3.43%). The percentage of malignant transformation was
      12.19% for untreated patients and 1.41% for treated patients. The floor of the
      oral cavity was proven to be the location of the highest risk of oral squamous
      cell carcinoma. Patients with diabetes may be more likely to develop OL. The risk
      of malignant transformation is relatively high. In our material it was equal to
      3.43%. CONCLUSIONS: Cigarette smoking is the most important factor, which can
      influence the effectiveness of treatment.

PMID- 25610348
TI  - Topical microemulsion containing Punica granatum extract: its control over skin
      erythema and melanin in healthy Asian subjects.
AB  - INTRODUCTION: Punica granatum is apotent source of polyphenolic compounds with
      strong free radicals scavenging activity. The skin lightening effects of Punica
      granatum are assumed due to ellagic acid which acts by chelating copper at the
      active site of tyrosinase. AIM: To explore a topical microemulsion (O/W) of
      pomegranate (Punica granatum) extract for its control on skin erythema and
      melanin. MATERIAL AND METHODS: Microemulsions were formulated using a polysorbate
      surfactant (Tween 80((r))) along with cosurfactant (propylene glycol) and were
      characterized regarding their stability. The placebo microemulsion (without
      extract) and the active microemulsion (containing Punica extract) were applied in
      a split face fashion by the volunteers (n = 11) for a period of 12 weeks. Skin
      erythema and melanin were measured at baseline and after every 15 days to
      determine any effect produced by these formulations. RESULTS: Active formulation
      showed a significant impact on skin erythema and melanin (p < 0.05). CONCLUSIONS:
      This study reveals that a suitable topical formulation like microemulsion could
      employ the Punica granatum extract for conditions where elevated skin melanin and
      erythema have significantly prone skin physiology.

PMID- 25610349
TI  - Acne in hirsute women.
AB  - INTRODUCTION: Acne and hirsutism are common manifestations of hyperandrogenism.
      AIM: To investigate whether or not acne is present in women with hirsutism,
      associated with different clinical, endocrine and ultrasonographic features.
      MATERIAL AND METHODS: The prospective study included 135 women with hirsutism,
      aged 14-46 years. We measured the levels of hormones with
      radioimmunoassay/immunoradiometric assay methods. RESULTS: Acne were present in
      63 (47.6%) women with hirsutism. Sixty women had mild forms of acne, including:
      whiteheads, blackheads, papules and pustules. Only 3 women had moderate to severe
      acne, including nodules. In a group of women with hirsutism and acne, 6 (9.5%)
      were obese. In our study we found a high prevalence of androgen excess among
      hirsute women with acne: total testosterone was increased in 79%, free
      testosterone in 20.6%, androstenedione in 69.8%, dehydroepiandrosterone sulfate
      (DHEAS) in 30.1%, 17-OH-progesterone 68.2% and sex hormone-binding globulin
      (SHBG) was decreased in 33.3% of women. Women with hirsutism and acne have
      received oral contraceptives for a year, without or in a combination with other
      medication. Thirty-four (53.9%) women have shown improvement in hirsutism and
      acne. CONCLUSIONS: In this study we found a high prevalence of acne in hirsute
      women. The prevalence of acne was higher in polycystic ovarian syndrome. Since
      these women have associated endocrine changes it is important to correct them
      with hormonal therapy.

PMID- 25610350
TI  - Dermoscopic and clinical features of trunk melanomas.
AB  - INTRODUCTION: Malignant melanomas account for 5% of all skin cancers and usually
      have a fatal clinical course. Additionally, the incidence of melanoma increases
      more rapidly than in any other cancer, and this has been attributed to the
      development of highly sensitive diagnostic techniques, mainly dermoscopy, which
      allows for early diagnosis. The phenotypic manifestations of gene/environment
      interactions, environmental factor and genetic factors may determine subtypes and
      anatomic localization of melanoma. Histopathologic subtypes, risk factors, and
      thickness of the skin are different in trunk melanomas. AIM: To determine the
      frequency of dermatoscopic features in trunk melanomas. This study also
      investigates dermoscopic features according to the diameter of lesions. MATERIAL
      AND METHODS: Seventy-one trunk melanomas were included. Their dermoscopic and
      clinical images, histopathological and clinical data were assessed. The relations
      between the diameter, Breslow thickness and dermoscopic characteristics were
      evaluated. RESULTS: The most common dermoscopic findings of trunk melanomas were
      the multicomponent pattern (55 patients, 77.5%), asymmetry (62 patients; 87.3%),
      blue-gray veil (59 patients, 83.1%), and color variety (56 patients, 78.8%). When
      dermoscopic findings were compared, a multicomponent pattern (p = 0.03), milky
      red areas (p = 0.001), blue-gray veils (p = 0.023), and regression structures (p
      = 0.037) were more common in large melanomas than in small melanomas.
      CONCLUSIONS: The most common dermoscopic findings of trunk melanomas were the
      multicomponent pattern, asymmetry and blue-gray veil, color variety. The
      multicomponent pattern, milky-red areas, blue-gray veils, regression structures
      were statistically significant dermoscopic features in a group of large-diameter
      melanomas, compared to small melanomas.

PMID- 25610351
TI  - Cutaneous drug reactions in children: a multicentric study.
AB  - INTRODUCTION: According to studies conducted in outpatients, it is estimated that
      2.5% of children who are treated with a drug will experience a cutaneous adverse
      drug reaction (CADR). AIM: To analyze the CADR reports involving pediatric
      patients recorded by three different university hospitals for describing common,
      serious, and interesting cutaneous drug eruption patterns. MATERIAL AND METHODS:
      For this purpose, the patients' data from three different universities were
      reviewed retrospectively. Diagnosis was based on history, clinical findings and
      laboratory test results. The CADRs were classified into seven categories;
      urticaria, angioedema, maculopapular eruption, fixed drug eruption, erythema
      multiforme, acute generalized exanthematous pustulosis, drug rash with
      eosinophilia and systemic symptoms syndrome. RESULTS: A total of 122 patients who
      had CADRs were enrolled in the study. The most frequently detected cutaneous drug
      reactions were urticaria + angioedema. Most of patients had no previous
      experience with the same drug and the most common causative agent of CADRs was
      antimicrobials. CONCLUSIONS: Since CADRs are relatively rare, the current
      multicentric study can provide meaningful information about the cutaneous
      eruption patterns of commonly used drugs.

PMID- 25610352
TI  - Asthma-chronic obstructive pulmonary disease overlap syndrome in Poland. Findings
      of an epidemiological study.
AB  - INTRODUCTION: Recent years have seen an increased interest in asthma-chronic
      obstructive pulmonary disease (COPD) overlap syndrome (ACOS). AIM: In 2012,
      Takeda Polska conducted a non-interventional epidemiological study aimed at
      identifying the typical phenotype of ACOS patients receiving pulmonary care.
      MATERIAL AND METHODS: The study enrolled a total of 12,103 of smoking patients
      above 45 years of age (mean age: 61.5 years; mean duration of smoking: 28.4 pack
      years). A total of 68.6% of patients represented the frequent-exacerbation
      phenotype (mean number of exacerbations during 12 months: 2.11), and 56.4% of
      patients from the group comprising 12,103 participants were hospitalized at least
      once during their lifetime due to a respiratory system disease (mean number: 3.82
      +/-3.76). RESULTS: The most commonly found asthma symptoms included paroxysmal
      dyspnoea with wheezing, and good response to inhaled steroids. The most
      frequently identified COPD-associated symptoms were: long-lasting reduction in
      forced expiratory volume in 1 s (FEV1) (< 80% after administering a
      bronchodilator) and chronic productive cough. Eighty-five percent of patients
      were diagnosed with concomitant diseases, predominantly arterial hypertension
      (62.9%) and metabolic diseases (metabolic syndrome, obesity, type 2 diabetes -
      46.4% in total). CONCLUSIONS: A clinically severe course of ACOS and the presence
      of concomitant diseases should be regarded as factors justifying an individual
      selection of inhalation therapy which specifically takes into account anti
      inflammatory treatment and patient safety.

PMID- 25610353
TI  - The use of reflectance confocal microscopy for examination of benign and
      malignant skin tumors.
AB  - Reflectance confocal microscopy (RCM) is a modern, non-invasive diagnostic method
      that enables real-time imaging of epidermis and upper layers of the dermis with a
      nearly histological precision and high contrast. The application of this
      technology in skin imaging in the last few years has resulted in the progress of
      dermatological diagnosis, providing virtual access to the living skin erasing the
      need for conventional histopathology. The RCM has a potential of wide application
      in the dermatological diagnostic process with a particular reference to benign
      and malignant skin tumors. This article provides a summary of the latest reports
      and previous achievements in the field of RCM application in the diagnostic
      process of skin neoplasms. A range of dermatological indications and general
      characteristics of confocal images in various types of tumors are presented. 

PMID- 25610354
TI  - Volumetric techniques: three-dimensional midface modeling.
AB  - Aging is a complex process caused by many factors. The most important factors
      include exposure to UV radiation, smoking, facial muscle movement, gravity, loss
      and displacement of fat and bone resorption. As a symptom of aging, face loses
      elasticity, volume and cheerful look. While changing face proportions, the
      dominant part of a face is its bottom instead of the mid part. The use of three
      dimensional face modelling techniques, particularly the mid-face - tear through
      and cheeks, restores the skin firmness, volume and healthy look. For this purpose
      the hyaluronic acid is used, calcium hydroxyapatite, and L-polylactic acid
      fillers. Volumetric techniques require precision and proper selection of the
      filling agent to give a sense of satisfaction to both the patient and the doctor.

PMID- 25610355
TI  - The possibilities and principles of methotrexate treatment of psoriasis - the
      updated knowledge.
AB  - Psoriasis is a chronic multifactorial disease affecting 2-4% of the general
      population. Due to its nature, psoriasis has a negative impact on the quality of
      life of patients. Therefore, the choice of an appropriate and individually
      tailored treatment controlling the symptoms of the disorder is necessary and
      continues to be a challenge for dermatologists. Therapeutic modalities in
      psoriasis should on the one hand be effective and on the other hand present a
      good safety profile. Methotrexate (MTX) is one of treatment options for psoriasis
      and can be administered both as monotherapy or in combination schemes. The paper
      presents the current state of knowledge about the possible treatment of psoriatic
      patients with MTX according to contemporary guidelines. 

PMID- 25610356
TI  - DRESS syndrome as a complication of treatment of hepatitis C virus-associated
      post-inflammatory liver cirrhosis with peginterferon alpha2a and ribavirin.
AB  - Various skin and systemic symptoms may develop as a complication of treatment
      with different medications and medicinal substances. One of them is a relatively
      rare drug reaction with eosinophilia and systemic symptoms, referred to as DRESS
      syndrome. The morphology of skin lesions and the patient's general health can
      differ; the management involves withdrawal of drugs suspected of triggering DRESS
      syndrome, and administration of local and systemic glucocorticosteroids. In this
      paper we present a case of a patient with HCV associated chronic hepatitis,
      treated with peginterferon alpha2a (PEG-IFN-alpha2a) and ribavirin, who developed
      skin lesions and systemic symptoms typical of DRESS syndrome. 

PMID- 25610357
TI  - Surgical treatment of skin lesions in lupus erythematosus.
AB  - Lipodystrophies are a wide group of diseases with various etiology, mainly
      genetic, metabolic or autoimmune. The treatment of these diseases is chronic and
      not always effective. Major concerns for patients with lipodystrophies are also
      esthetic defects, especially deformities in the face, neck and upper limbs. There
      are many surgical methods that can be used to improve patient's appearance like
      fillers, autologous fat transfer and skin flaps. The aim of this paper is to
      present and discuss surgical techniques used for correction of lipoatrophy and
      other skin lesions present in lupus erythematosus. In the first presented
      patient, lipodermal grafts were performed in two stages (first - to both
      zygomatic areas, the second - to both nasolabial folds). Moreover, the patient
      was qualified for arm scar plasty. Deepithelialized skin in the affected area was
      covered with advanced local skin flaps. In the second patient, an extensive
      scarring lesion on the scalp was excised and the defect was closed with an
      expanded scalp flap. Patients with lipodystrophies may require aesthetic surgical
      procedures to improve their appearance. In patients with lupus erythematosus,
      autologous fat graft in the face area seems to be a safe and effective method of
      refilling the volume of atrophic tissues. On the basis of our experience, it is
      worth emphasizing that the process of fat graft resorption is typical. In
      patients with scalp scars, an effective method of their removal and hairline
      restoring is usage of the tissue expander. 

PMID- 25610358
TI  - Segmental neurofibromatosis.
AB  - Segmental neurofibromatosis or type V neurofibromatosis is a rare genodermatosis
      characterized by neurofibromas, cafe-au-lait spots and neurofibromas limited to a
      circumscribed body region. The disease may be associated with systemic
      involvement and malignancies. The disorder has not been reported yet in the
      Polish medical literature. A 63-year-old Caucasian woman presented with a 20-year
      history of multiple, flesh colored, dome-shaped, soft to firm nodules situated in
      the right lumbar region. A histopathologic evaluation of three excised tumors
      revealed neurofibromas. No neurological and ophthalmologic symptoms of
      neurofibromatosis were diagnosed. 

PMID- 25610359
TI  - Can biologic treatment induce cutaneous focal mucinosis?
AB  - Skin mucinosis is a rare skin disease which clinically manifests as firm papules
      and waxy nodules. We report a case of a 66-year-old female psoriatic patient who
      developed skin mucinosis during biological therapy. Because of a previous lack of
      response to the local and conventional systemic treatment of psoriasis, the
      patient received biological therapy (infliximab from June 2008 to May 2009 -
      initial clinical improvement and loss of treatment effectiveness in the 36(th)
      week of the therapy; adalimumab from June 2009 to January 2010 - lack
      effectiveness; ustekinumab from March 2012 to the present). Throughout 2 months
      we observed a manifestation of the skin mucinosis as well-demarcated, yellow and
      brown, papulo-nodular lesions of 5-10 mm in diameter, localized on the back.
      Histopathological examination with alcian blue staining demonstrated mucin
      deposits in the dermis. On the basis of clinical and histopathological findings,
      the diagnosis of cutaneous focal mucinosis was established. We present the case
      because of the extremely rare occurrence of the disease. Scarce literature and
      data suggest that there is an association between focal mucinosis and thyroid
      dysfunction, as well as possible adverse effects of biological therapy with TNF
      alpha antagonists. 

PMID- 25610360
TI  - Behcet's disease leaves the silk road.
AB  - Behcet's disease is rarely recognized among Caucasians, while it is endemic in
      countries of the Eastern and Central Asia, especially in Turkey. The aim of the
      manuscript is to present the clinical picture, diagnosis criteria and therapeutic
      approaches of this rare disease which, because of intensive migration, can occur
      not only in particular regions of the world. 

PMID- 25610361
TI  - Tinea cutis glabrae: causes of diagnostic challenge.
AB  - Dermatophytoses belong to the most common disease entities encountered in
      everyday dermatological practice. Despite the fact that their clinical
      presentation, course and treatment response remain rather typical, they often
      present a considerable diagnostic and therapeutic challenge. We present a case of
      a 54-year-old male who presented to the outpatient clinic of the Department of
      Dermatology in December 2012 with the diagnosis of erythema gyratum repens for
      further diagnosis and treatment of skin lesions gradually intensifying in the
      previous 2 years. The skin changes presented as spreading annular erythematous
      lesions, with papules and plaques located peripherally, and accompanying
      pruritus. Due to the clinical presentation and anamnesis, working conditions
      (poultry farm), and lack of response to previous treatment, mycological culture
      was performed. Epithelial scrapings of the trunk and the groins proved to be
      positive. After 3 weeks, Trichophyton mentagrophytes var mentagrophytes was
      identified by epithelial cell culture. 

PMID- 25610362
TI  - Two cases of Degos disease with different prognosis.

PMID- 25610365
TI  - Spinal cord injury increases the reactivity of rat tail artery to angiotensin II.
AB  - Studies in individuals with spinal cord injury (SCI) suggest the vasculature is
      hyperreactive to angiotensin II (Ang II). In the present study, the effects of
      SCI on the reactivity of the rat tail and mesenteric arteries to Ang II have been
      investigated. In addition, the effects of SCI on the facilitatory action of Ang
      II on nerve-evoked contractions of these vessels were determined. Isometric
      contractions of artery segments from T11 (tail artery) or T4 (mesenteric
      arteries) spinal cord-transected rats and sham-operated rats were compared 6-7
      weeks postoperatively. In both tail and mesenteric arteries, SCI increased nerve
      evoked contractions. In tail arteries, SCI also greatly increased Ang II-evoked
      contractions and the facilitatory effect of Ang II on nerve-evoked contractions.
      By contrast, SCI did not detectably change the responses of mesenteric arteries
      to Ang II. These findings provide the first direct evidence that SCI increases
      the reactivity of arterial vessels to Ang II. In addition, in tail artery, the
      findings indicate that Ang II may contribute to modifying their responses
      following SCI. 

PMID- 25610366
TI  - Chronic pramipexole treatment increases tolerance for sucrose in normal and
      ventral tegmental lesioned rats.
AB  - The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe
      motor control deficits which are reduced by the use of dopamine agonists.
      However, recent works have indicated that D3-preferential agonists such as
      pramipexole can induce impulse control disorders (ICDs) such as food craving or
      compulsive eating. In the present study, we performed an intermittent daily
      feeding experiment to assess the effect of chronic treatment by pramipexole and
      VTA bilateral lesion on tolerance for sucrose solution. The impact of such
      chronic treatment on spontaneous locomotion and spatial memory was also examined.
      Changes in sucrose tolerance could indicate the potential development of a change
      in food compulsion or addiction related to the action of pramipexole. Neither the
      bilateral lesion of the VTA nor chronic treatment with pramipexole altered the
      spontaneous locomotion or spatial memory in rats. Rats without pramipexole
      treatment quickly developed a stable intake of sucrose solution in the 12 h
      access phase. On the contrary, when under daily pramipexole treatment, rats
      developed a stronger and ongoing escalation of their sucrose solution intakes. In
      addition, we noted that the change in sucrose consumption was sustained by an
      increase of the expression of the Dopamine D3 receptor in the core and the shell
      regions of the nucleus accumbens. The present results may suggest that long-term
      stimulation of the Dopamine D3 receptor in animals induces a strong increase in
      sucrose consumption, indicating an effect of this receptor on certain
      pathological aspects of food eating. 

PMID- 25610364
TI  - Revealing neuronal function through microelectrode array recordings.
AB  - Microelectrode arrays and microprobes have been widely utilized to measure
      neuronal activity, both in vitro and in vivo. The key advantage is the capability
      to record and stimulate neurons at multiple sites simultaneously. However, unlike
      the single-cell or single-channel resolution of intracellular recording,
      microelectrodes detect signals from all possible sources around every sensor.
      Here, we review the current understanding of microelectrode signals and the
      techniques for analyzing them. We introduce the ongoing advancements in
      microelectrode technology, with focus on achieving higher resolution and quality
      of recordings by means of monolithic integration with on-chip circuitry. We show
      how recent advanced microelectrode array measurement methods facilitate the
      understanding of single neurons as well as network function. 

PMID- 25610363
TI  - Influence of sex and stress exposure across the lifespan on endophenotypes of
      depression: focus on behavior, glucocorticoids, and hippocampus.
AB  - Sex differences exist in vulnerability, symptoms, and treatment of many
      neuropsychiatric disorders. In this review, we discuss both preclinical and
      clinical research that investigates how sex influences depression endophenotypes
      at the behavioral, neuroendocrine, and neural levels across the lifespan. Chronic
      exposure to stress is a risk factor for depression and we discuss how stress
      during the prenatal, postnatal, and adolescent periods differentially affects
      males and females depending on the method of stress and metric examined. Given
      that the integrity of the hippocampus is compromised in depression, we
      specifically focus on sex differences in how hippocampal plasticity is affected
      by stress and depression across the lifespan. In addition, we examine how female
      physiology predisposes depression in adulthood, specifically in postpartum and
      perimenopausal periods. Finally, we discuss the underrepresentation of women in
      both preclinical and clinical research and how this limits our understanding of
      sex differences in vulnerability, presentation, and treatment of depression. 

PMID- 25610367
TI  - Roles of the ubiquitin proteasome system in the effects of drugs of abuse.
AB  - Because of its ability to regulate the abundance of selected proteins the
      ubiquitin proteasome system (UPS) plays an important role in neuronal and
      synaptic plasticity. As a result various stages of learning and memory depend on
      UPS activity. Drug addiction, another phenomenon that relies on neuroplasticity,
      shares molecular substrates with memory processes. However, the necessity of
      proteasome-dependent protein degradation for the development of addiction has
      been poorly studied. Here we first review evidences from the literature that
      drugs of abuse regulate the expression and activity of the UPS system in the
      brain. We then provide a list of proteins which have been shown to be targeted to
      the proteasome following drug treatment and could thus be involved in neuronal
      adaptations underlying behaviors associated with drug use and abuse. Finally we
      describe the few studies that addressed the need for UPS-dependent protein
      degradation in animal models of addiction-related behaviors. 

PMID- 25610369
TI  - Polarized cellular patterns of endocannabinoid production and detection shape
      cannabinoid signaling in neurons.
AB  - Neurons display important differences in plasma membrane composition between
      somatodendritic and axonal compartments, potentially leading to currently
      unexplored consequences in G-protein-coupled-receptor signaling. Here, by using
      highly-resolved biosensor imaging to measure local changes in basal levels of key
      signaling components, we explored features of type-1 cannabinoid receptor (CB1R)
      signaling in individual axons and dendrites of cultured rat hippocampal neurons.
      Activation of endogenous CB1Rs led to rapid, Gi/o-protein- and cAMP-mediated
      decrease of cyclic-AMP-dependent protein kinase (PKA) activity in the
      somatodendritic compartment. In axons, PKA inhibition was significantly stronger,
      in line with axonally-polarized distribution of CB1Rs. Conversely, inverse
      agonist AM281 produced marked rapid increase of basal PKA activation in somata
      and dendrites, but not in axons, removing constitutive activation of CB1Rs
      generated by local production of the endocannabinoid 2-arachidonoylglycerol (2
      AG). Interestingly, somatodendritic 2-AG levels differently modified signaling
      responses to CB1R activation by Delta(9)-THC, the psychoactive compound of
      marijuana, and by the synthetic cannabinoids WIN55,212-2 and CP55,940. These
      highly contrasted differences in sub-neuronal signaling responses warrant caution
      in extrapolating pharmacological profiles, which are typically obtained in non
      polarized cells, to predict in vivo responses of axonal (i.e., presynaptic)
      GPCRs. Therefore, our results suggest that enhanced comprehension of GPCR
      signaling constraints imposed by neuronal cell biology may improve the
      understanding of neuropharmacological action. 

PMID- 25610368
TI  - Gap junction proteins and their role in spinal cord injury.
AB  - Gap junctions are specialized intercellular communication channels that are
      formed by two hexameric connexin hemichannels, one provided by each of the two
      adjacent cells. Gap junctions and hemichannels play an important role in
      regulating cellular metabolism, signaling, and functions in both normal and
      pathological conditions. Following spinal cord injury (SCI), there is damage and
      disturbance to the neuronal elements of the spinal cord including severing of
      axon tracts and rapid cell death. The initial mechanical disruption is followed
      by multiple secondary cascades that cause further tissue loss and dysfunction.
      Recent studies have implicated connexin proteins as playing a critical role in
      the secondary phase of SCI by propagating death signals through extensive glial
      networks. In this review, we bring together past and current studies to outline
      the distribution, changes and roles of various connexins found in neurons and
      glial cells, before and in response to SCI. We discuss the contribution of
      pathologically activated connexin proteins, in particular connexin 43, to
      functional recovery and neuropathic pain, as well as providing an update on
      potential connexin specific pharmacological agents to treat SCI. 

PMID- 25610370
TI  - Neurodevelopmental origin and adult neurogenesis of the neuroendocrine
      hypothalamus.
AB  - The adult hypothalamus regulates many physiological functions and homeostatic
      loops, including growth, feeding and reproduction. In mammals, the hypothalamus
      derives from the ventral diencephalon where two distinct ventricular
      proliferative zones have been described. Although a set of transcription factors
      regulating the hypothalamic development has been identified, the exact molecular
      mechanisms that drive the differentiation of hypothalamic neural precursor cells
      (NPCs) toward specific neuroendocrine neuronal subtypes is yet not fully
      disclosed. Neurogenesis has been also reported in the adult hypothalamus at the
      level of specific niches located in the ventrolateral region of ventricle wall,
      where NPCs have been identified as radial glia-like tanycytes. Here we review the
      molecular and cellular systems proposed to support the neurogenic potential of
      developing and adult hypothalamic NPCs. We also report new insights on the
      mechanisms by which adult hypothalamic neurogenesis modulates key functions of
      this brain region. Finally, we discuss how environmental factors may modulate the
      adult hypothalamic neurogenic cascade. 

PMID- 25610371
TI  - Cerebellar transcriptional alterations with Purkinje cell dysfunction and loss in
      mice lacking PGC-1alpha.
AB  - Alterations in the expression and activity of the transcriptional coactivator
      peroxisome proliferator-activated receptor gamma coactivator-1alpha (ppargc1a or
      PGC-1alpha) have been reported in multiple movement disorders, yet it is unclear
      how a lack of PGC-1alpha impacts transcription and function of the cerebellum, a
      region with high PGC-1alpha expression. We show here that mice lacking PGC-1alpha
      exhibit ataxia in addition to the previously described deficits in motor
      coordination. Using q-RT-PCR in cerebellar homogenates from PGC-1alpha(-/-) mice,
      we measured expression of 37 microarray-identified transcripts upregulated by PGC
      1alpha in SH-SY5Y neuroblastoma cells with neuroanatomical overlap with PGC
      1alpha or parvalbumin (PV), a calcium buffer highly expressed by Purkinje cells.
      We found significant reductions in transcripts with synaptic (complexin1, Cplx1;
      Pacsin2), structural (neurofilament heavy chain, Nefh), and metabolic (isocitrate
      dehydrogenase 3a, Idh3a; neutral cholesterol ester hydrolase 1, Nceh1; pyruvate
      dehydrogenase alpha 1, Pdha1; phytanoyl-CoA hydroxylase, Phyh; ubiquinol
      cytochrome c reductase, Rieske iron-sulfur polypeptide 1, Uqcrfs1) functions.
      Using conditional deletion of PGC-1alpha in PV-positive neurons, we determined
      that 50% of PGC-1alpha expression and a reduction in a subset of these
      transcripts could be explained by its concentration in PV-positive neuronal
      populations in the cerbellum. To determine whether there were functional
      consequences associated with these changes, we conducted stereological counts and
      spike rate analysis in Purkinje cells, a cell type rich in PV, from PGC-1alpha(-/
      ) mice. We observed a significant loss of Purkinje cells by 6 weeks of age, and
      the remaining Purkinje cells exhibited a 50% reduction in spike rate. Together,
      these data highlight the complexity of PGC-1alpha's actions in the central
      nervous system and suggest that dysfunction in multiple cell types contribute to
      motor deficits in the context of PGC-1alpha deficiency. 

PMID- 25610372
TI  - Calcium current homeostasis and synaptic deficits in hippocampal neurons from
      Kelch-like 1 knockout mice.
AB  - Kelch-like 1 (KLHL1) is a neuronal actin-binding protein that modulates voltage
      gated CaV2.1 (P/Q-type) and CaV3.2 (alpha1H T-type) calcium channels; KLHL1
      knockdown experiments (KD) cause down-regulation of both channel types and
      altered synaptic properties in cultured rat hippocampal neurons (Perissinotti et
      al., 2014). Here, we studied the effect of ablation of KLHL1 on calcium channel
      function and synaptic properties in cultured hippocampal neurons from KLHL1
      knockout (KO) mice. Western blot data showed the P/Q-type channel alpha1A subunit
      was less abundant in KO hippocampus compared to wildtype (WT); and P/Q-type
      calcium currents were smaller in KO neurons than WT during early days in vitro,
      although this decrease was compensated for at late stages by increases in L-type
      calcium current. In contrast, T-type currents did not change in culture. However,
      biophysical properties and western blot analysis revealed a differential
      contribution of T-type channel isoforms in the KO, with CaV3.2 alpha1H subunit
      being down-regulated and CaV3.1 alpha1G up-regulated. Synapsin I levels were also
      reduced in the KO hippocampus and cultured neurons displayed a concomitant
      reduction in synapsin I puncta and decreased miniature excitatory postsynaptic
      current (mEPSC) frequency. In summary, genetic ablation of the calcium channel
      modulator resulted in compensatory mechanisms to maintain calcium current
      homeostasis in hippocampal KO neurons; however, synaptic alterations resulted in
      a reduction of excitatory synapse number, causing an imbalance of the excitatory
      inhibitory synaptic input ratio favoring inhibition. 

PMID- 25610374
TI  - Sonic hedgehog signaling in the development of the mouse hypothalamus.
AB  - The expression pattern of Sonic Hedgehog (Shh) in the developing hypothalamus
      changes over time. Shh is initially expressed in the prechordal mesoderm and
      later in the hypothalamic neuroepithelium-first medially, and then in two off
      medial domains. This dynamic expression suggests that Shh might regulate several
      aspects of hypothalamic development. To gain insight into them, lineage tracing,
      (conditional) gene inactivation in mouse, in ovo loss- and gain-of-function
      approaches in chick and analysis of Shh expression regulation have been employed.
      We will focus on mouse studies and refer to chick and fish when appropriate to
      clarify. These studies show that Shh-expressing neuroepithelial cells serve as a
      signaling center for neighboring precursors, and give rise to most of the basal
      hypothalamus (tuberal and mammillary regions). Shh signaling is initially
      essential for hypothalamic induction. Later, Shh signaling from the
      neuroepithelium controls specification of the lateral hypothalamic area and
      growth-patterning coordination in the basal hypothalamus. To further elucidate
      the role of Shh in hypothalamic development, it will be essential to understand
      how Shh regulates the downstream Gli transcription factors. 

PMID- 25610373
TI  - Regulation of cerebral cortex development by Rho GTPases: insights from in vivo
      studies.
AB  - The cerebral cortex is the site of higher human cognitive and motor functions.
      Histologically, it is organized into six horizontal layers, each containing
      unique populations of molecularly and functionally distinct excitatory projection
      neurons and inhibitory interneurons. The stereotyped cellular distribution of
      cortical neurons is crucial for the formation of functional neural circuits and
      it is predominantly established during embryonic development. Cortical neuron
      development is a multiphasic process characterized by sequential steps of neural
      progenitor proliferation, cell cycle exit, neuroblast migration and neuronal
      differentiation. This series of events requires an extensive and dynamic
      remodeling of the cell cytoskeleton at each step of the process. As major
      regulators of the cytoskeleton, the family of small Rho GTPases has been shown to
      play essential functions in cerebral cortex development. Here we review in vivo
      findings that support the contribution of Rho GTPases to cortical projection
      neuron development and we address their involvement in the etiology of cerebral
      cortex malformations. 

PMID- 25610375
TI  - Characterization of a mammalian prosencephalic functional plan.
AB  - Hypothalamic organizational concepts have greatly evolved as the primary
      hypothalamic pathways have been systematically investigated. In the present
      review, we describe how the hypothalamus arises from a molecularly heterogeneous
      region of the embryonic neural tube but is first differentiated as a primary
      neuronal cell cord (earliest mantle layer). This structure defines two axes that
      align onto two fundamental components: a longitudinal tractus
      postopticus(tpoc)/retinian component and a transverse supraoptic
      tract(sot)/olfactory component. We then discuss how these two axonal tracts guide
      the formation of all major tracts that connect the telencephalon with the
      hypothalamus/ventral midbrain, highlighting the existence of an early basic plan
      in the functional organization of the prosencephalic connectome. 

PMID- 25610376
TI  - Upper esophageal sphincter mechanical states analysis: a novel methodology to
      describe UES relaxation and opening.
AB  - The swallowing muscles that influence upper esophageal sphincter (UES) opening
      are centrally controlled and modulated by sensory information. Activation of
      neural inputs to these muscles, the intrinsic cricopharyngeus muscle and
      extrinsic suprahyoid muscles, results in their contraction or relaxation, which
      changes the diameter of the lumen, alters the intraluminal pressure and
      ultimately inhibits or promotes flow of content. This relationship that exists
      between the changes in diameter and concurrent changes in intraluminal pressure
      has been used previously to calculate the "mechanical states" of the muscle; that
      is when the muscles are passively or actively, relaxing or contracting. Diseases
      that alter the neural pathways to these muscles can result in weakening the
      muscle contractility and/or decreasing the muscle compliance, all of which can
      cause dysphagia. Detecting these changes in the mechanical state of the muscle is
      difficult and as the current interpretation of UES motility is based largely upon
      pressure measurement (manometry), subtle changes in the muscle function during
      swallow can be missed. We hypothesized that quantification of mechanical states
      of the UES and the pressure-diameter properties that define them, would allow
      objective characterization of the mechanisms that govern the timing and extent of
      UES opening during swallowing. To achieve this we initially analyzed swallows
      captured by simultaneous videofluoroscopy and UES pressure with impedance
      recording. From these data we demonstrated that intraluminal impedance
      measurements could be used to determine changes in the internal diameter of the
      lumen when compared to videofluoroscopy. Then using a database of pressure
      impedance studies, recorded from young and aged healthy controls and patients
      with motor neuron disease, we calculated the UES mechanical states in relation to
      a standardized swallowed bolus volume, normal aging and dysphagia pathology. Our
      results indicated that eight different mechanical states were almost always seen
      during healthy swallowing and some of these calculated changes in muscle function
      were consistent with the known neurally dependent phasic discharge patterns of
      cricopharyngeus muscle activity during swallowing. Clearly defined changes in the
      mechanical states were observed in motor neuron disease when compared to age
      matched healthy controls. Our data indicate that mechanical state predictions
      were simple to apply and revealed patterns consistent with the known neural
      inputs activating the different muscles during swallowing. 

PMID- 25610378
TI  - Independent effects of bottom-up temporal expectancy and top-down spatial
      attention. An audiovisual study using rhythmic cueing.
AB  - Selective attention to a spatial location has shown enhanced perception and
      facilitate behavior for events at attended locations. However, selection relies
      not only on where but also when an event occurs. Recently, interest has turned to
      how intrinsic neural oscillations in the brain entrain to rhythms in our
      environment, and, stimuli appearing in or out of sync with a rhythm have shown to
      modulate perception and performance. Temporal expectations created by rhythms and
      spatial attention are two processes which have independently shown to affect
      stimulus processing but it remains largely unknown how, and if, they interact. In
      four separate tasks, this study investigated the effects of voluntary spatial
      attention and bottom-up temporal expectations created by rhythms in both unimodal
      and crossmodal conditions. In each task the participant used an informative cue,
      either color or pitch, to direct their covert spatial attention to the left or
      right, and respond as quickly as possible to a target. The lateralized target
      (visual or auditory) was then presented at the attended or unattended side.
      Importantly, although not task relevant, the cue was a rhythm of either flashes
      or beeps. The target was presented in or out of sync (early or late) with the
      rhythmic cue. Results showed participants were faster responding to spatially
      attended compared to unattended targets in all tasks. Moreover, there was an
      effect of rhythmic cueing upon response times in both unimodal and crossmodal
      conditions. Responses were faster to targets presented in sync with the rhythm
      compared to when they appeared too early in both crossmodal tasks. That is,
      rhythmic stimuli in one modality influenced the temporal expectancy in the other
      modality, suggesting temporal expectancies created by rhythms are crossmodal.
      Interestingly, there was no interaction between top-down spatial attention and
      rhythmic cueing in any task suggesting these two processes largely influenced
      behavior independently. 

PMID- 25610377
TI  - Rethinking energy in parkinsonian motor symptoms: a potential role for neural
      metabolic deficits.
AB  - Parkinson's disease (PD) is characterized as a chronic and progressive
      neurodegenerative disorder that results in a variety of debilitating symptoms,
      including bradykinesia, resting tremor, rigidity, and postural instability.
      Research spanning several decades has emphasized basal ganglia dysfunction,
      predominantly resulting from dopaminergic (DA) cell loss, as the primarily cause
      of the aforementioned parkinsonian features. But, why those particular features
      manifest themselves remains an enigma. The goal of this paper is to develop a
      theoretical framework that parkinsonian motor features are behavioral consequence
      of a long-term adaptation to their inability (inflexibility or lack of capacity)
      to meet energetic demands, due to neural metabolic deficits arising from
      mitochondrial dysfunction associated with PD. Here, we discuss neurophysiological
      changes that are generally associated with PD, such as selective degeneration of
      DA neurons in the substantia nigra pars compacta (SNc), in conjunction with
      metabolic and mitochondrial dysfunction. We then characterize the cardinal motor
      symptoms of PD, bradykinesia, resting tremor, rigidity and gait disturbance,
      reviewing literature to demonstrate how these motor patterns are actually energy
      efficient from a metabolic perspective. We will also develop three testable
      hypotheses: (1) neural metabolic deficits precede the increased rate of
      neurodegeneration and onset of behavioral symptoms in PD; (2) motor behavior of
      persons with PD are more sensitive to changes in metabolic/bioenergetic state;
      and (3) improvement of metabolic function could lead to better motor performance
      in persons with PD. These hypotheses are designed to introduce a novel viewpoint
      that can elucidate the connections between metabolic, neural and motor function
      in PD. 

PMID- 25610380
TI  - The bio-distribution of the antidepressant clomipramine is modulated by chronic
      stress in mice: effects on behavior.
AB  - Major depression (MD) is one of the most common psychiatric disorders, severely
      affecting the quality of life of millions of people worldwide. Despite the
      availability of several classes of antidepressants, treatment efficacy is still
      very variable and many patients do not respond to the treatment. Clomipramine
      (CMI), a classical and widely used antidepressant, shows widespread
      interindividual variability of efficacy, while the environmental factors
      contributing to such variability remain unclear. We investigated whether chronic
      stress modulates the bio-distribution of CMI, and as a result the behavioral
      response to CMI treatment in a mouse model of chronic social defeat stress
      (CSDS). Our results show that stress exposure increased anxiety-like and
      depressive-like behaviors and altered the stress response. Chronic defeat stress
      furthermore significantly altered CMI bio-distribution. Interestingly, CMI bio
      distribution highly correlated with anxiety-like and depressive-like behaviors
      only under basal conditions. Taken together, we provide first evidence
      demonstrating that chronic stress exposure modulates CMI bio-distribution and
      behavioral responses. This may contribute to CMI's broad interindividual
      variability, and is especially relevant in clinical practice. 

PMID- 25610379
TI  - Behavioral impairments in animal models for zinc deficiency.
AB  - Apart from teratogenic and pathological effects of zinc deficiency such as the
      occurrence of skin lesions, anorexia, growth retardation, depressed wound
      healing, altered immune function, impaired night vision, and alterations in taste
      and smell acuity, characteristic behavioral changes in animal models and human
      patients suffering from zinc deficiency have been observed. Given that it is
      estimated that about 17% of the worldwide population are at risk for zinc
      deficiency and that zinc deficiency is associated with a variety of brain
      disorders and disease states in humans, it is of major interest to investigate,
      how these behavioral changes will affect the individual and a putative course of
      a disease. Thus, here, we provide a state of the art overview about the
      behavioral phenotypes observed in various models of zinc deficiency, among them
      environmentally produced zinc deficient animals as well as animal models based on
      a genetic alteration of a particular zinc homeostasis gene. Finally, we compare
      the behavioral phenotypes to the human condition of mild to severe zinc
      deficiency and provide a model, how zinc deficiency that is associated with many
      neurodegenerative and neuropsychological disorders might modify the disease
      pathologies. 

PMID- 25610381
TI  - Acute stress in adulthood impoverishes social choices and triggers aggressiveness
      in preclinical models.
AB  - Adult C57BL/6J mice are known to exhibit high level of social flexibility while
      mice lacking the beta2 subunit of nicotinic receptors (beta2(-/-) mice) present
      social rigidity. We asked ourselves what would be the consequences of a restraint
      acute stress (45 min) on social interactions in adult mice of both genotypes,
      hence the contribution of neuronal nicotinic receptors in this process. We
      therefore dissected social interaction complexity of stressed and not stressed
      dyads of mice in a social interaction task. We also measured plasma
      corticosterone levels in our experimental conditions. We showed that a single
      stress exposure occurring in adulthood reduced and disorganized social
      interaction complexity in both C57BL/6J and beta2(-/-) mice. These stress-induced
      maladaptive social interactions involved alteration of distinct social categories
      and strategies in both genotypes, suggesting a dissociable impact of stress
      depending on the functioning of the cholinergic nicotinic system. In both
      genotypes, social behaviors under stress were coupled to aggressive reactions
      with no plasma corticosterone changes. Thus, aggressiveness appeared a general
      response independent of nicotinic function. We demonstrate here that a single
      stress exposure occurring in adulthood is sufficient to impoverish social
      interactions: stress impaired social flexibility in C57BL/6J mice whereas it
      reinforced beta2(-/-) mice behavioral rigidity. 

PMID- 25610382
TI  - Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs
      Long-Term Potentiation in Adulthood.
AB  - Changes in brain reward systems are thought to contribute significantly to the
      cognitive and behavioral impairments of schizophrenia, as well as the propensity
      to develop co-occurring substance abuse disorders. Presently, there are few
      treatments for persons with a dual diagnosis and little is known about the neural
      substrates that underlie co-occurring schizophrenia and substance abuse. One goal
      of the present study was to determine if a change in the concentration of
      kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of
      people with schizophrenia, affects reward-related behavior. KYNA is an endogenous
      antagonist of NMDA glutamate receptors and alpha7 nicotinic acetylcholine
      receptors, both of which are critically involved in neurodevelopment, plasticity,
      and behavior. In Experiment 1, rats were treated throughout adolescence with L
      kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug
      free in an autoshaping procedure in which a lever was paired with food. Rats
      treated with L-KYN during adolescence exhibited increased sign-tracking behavior
      (lever pressing) when they were tested as adults. Sign-tracking is thought to
      reflect the lever acquiring incentive salience (motivational value) as a result
      of its pairing with reward. Thus, KYNA exposure may increase the incentive
      salience of cues associated with reward, perhaps contributing to an increase in
      sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2,
      we tested the effects of exposure to KYNA during adolescence on hippocampal long
      term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst
      of high-frequency stimulation that was sufficient to produce robust LTP in
      vehicle-treated rats. This finding represents the first demonstrated consequence
      of elevated KYNA concentration during development and provides insight into the
      basis for cognitive and behavioral deficits that result from exposure to KYNA
      during adolescence. 

PMID- 25610383
TI  - Emotional language processing in autism spectrum disorders: a systematic review.
AB  - In his first description of Autism Spectrum Disorders (ASD), Kanner emphasized
      emotional impairments by characterizing children with ASD as indifferent to other
      people, self-absorbed, emotionally cold, distanced, and retracted. Thereafter,
      emotional impairments became regarded as part of the social impairments of ASD,
      and research mostly focused on understanding how individuals with ASD recognize
      visual expressions of emotions from faces and body postures. However, it still
      remains unclear how emotions are processed outside of the visual domain. This
      systematic review aims to fill this gap by focusing on impairments of emotional
      language processing in ASD. We systematically searched PubMed for papers
      published between 1990 and 2013 using standardized search terms. Studies show
      that people with ASD are able to correctly classify emotional language stimuli as
      emotionally positive or negative. However, processing of emotional language
      stimuli in ASD is associated with atypical patterns of attention and memory
      performance, as well as abnormal physiological and neural activity. Particularly,
      younger children with ASD have difficulties in acquiring and developing emotional
      concepts, and avoid using these in discourse. These emotional language
      impairments were not consistently associated with age, IQ, or level of
      development of language skills. We discuss how emotional language impairments fit
      with existing cognitive theories of ASD, such as central coherence, executive
      dysfunction, and weak Theory of Mind. We conclude that emotional impairments in
      ASD may be broader than just a mere consequence of social impairments, and should
      receive more attention in future research. 

PMID- 25610384
TI  - Pain sensitivity and tactile spatial acuity are altered in healthy musicians as
      in chronic pain patients.
AB  - Extensive training of repetitive and highly skilled movements, as it occurs in
      professional classical musicians, may lead to changes in tactile sensitivity and
      corresponding cortical reorganization of somatosensory cortices. It is also known
      that professional musicians frequently experience musculoskeletal pain and pain
      related symptoms during their careers. The present study aimed at understanding
      the complex interaction between chronic pain and music training with respect to
      somatosensory processing. For this purpose, tactile thresholds (mechanical
      detection, grating orientation, two-point discrimination) and subjective ratings
      to thermal and pressure pain stimuli were assessed in 17 professional musicians
      with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain,
      and 18 pain-free non-musicians. We found that pain-free musicians displayed
      greater touch sensitivity (i.e., lower mechanical detection thresholds), lower
      tactile spatial acuity (i.e., higher grating orientation thresholds) and
      increased pain sensitivity to pressure and heat compared to pain-free non
      musicians. Moreover, we also found that musicians and non-musicians with chronic
      pain presented lower tactile spatial acuity and increased pain sensitivity to
      pressure and heat compared to pain-free non-musicians. The significant increment
      of pain sensitivity together with decreased spatial discrimination in pain-free
      musicians and the similarity of results found in chronic pain patients, suggests
      that the extensive training of repetitive and highly skilled movements in
      classical musicians could be considered as a risk factor for developing chronic
      pain, probably due to use-dependent plastic changes elicited in somatosensory
      pathways. 

PMID- 25610385
TI  - Orientation-specific surround suppression in the primary visual cortex varies as
      a function of autistic tendency.
AB  - Individuals with autism spectrum disorder (ASD) exhibit superior performance on
      tasks that rely on local details in an image, and they exhibit deficits in tasks
      that require integration of local elements into a unified whole. These perceptual
      abnormalities have been proposed to underlie many of the characteristic features
      of ASD, but the underlying neural mechanisms are poorly understood. Here, we
      investigated the degree to which orientation-specific surround suppression, a
      well-known form of contextual modulation in visual cortex, is associated with
      autistic tendency in neurotypical (NT) individuals. Surround suppression refers
      to the phenomenon that the response to a stimulus in the receptive field of a
      neuron is suppressed when it is surrounded by stimuli just outside the receptive
      field. The suppression is greatest when the center and surrounding stimuli share
      perceptual features such as orientation. Surround suppression underlies a number
      of fundamental perceptual processes that are known to be atypical in individuals
      with ASD, including perceptual grouping and perceptual pop-out. However, whether
      surround suppression in the primary visual cortex (V1) is related to autistic
      traits has not been directly tested before. We used fMRI to measure the neural
      response to a center Gabor when it was surrounded by Gabors having the same or
      orthogonal orientation, and calculated a suppression index (SI) for each
      participant that denoted the magnitude of suppression in the same vs. orthogonal
      conditions. SI was positively correlated with degree of autistic tendency in each
      individual, as measured by the Autism Quotient (AQ) scale, a questionnaire
      designed to assess autistic traits in the general population. Age also correlated
      with SI and with autistic tendency in our sample, but did not account for the
      correlation between SI and autistic tendency. These results suggest a reduction
      in orientation-specific surround suppression in V1 with increasing autistic
      tendency. 

PMID- 25610386
TI  - An investigation of the neural substrates of mind wandering induced by viewing
      traditional Chinese landscape paintings.
AB  - The present study was conducted to investigate whether the calming effect induced
      by viewing traditional Chinese landscape paintings would make disengagement from
      that mental state more difficult, as measured by performance on a cognitive
      control task. In Experiment 1 we examined the subjective experience of viewing
      traditional Chinese landscape paintings vs. realistic oil landscape paintings in
      a behavioral study. Our results confirmed that, as predicted, traditional Chinese
      landscape paintings induce greater levels of relaxation and mind wandering and
      lower levels of object-oriented absorption and recognition, compared to realistic
      oil landscape paintings. In Experiment 2 we used functional Magnetic Resonance
      Imaging to explore the behavioral and neural effects of viewing traditional
      Chinese landscape paintings on a task requiring cognitive control (i.e., the
      flanker task)-administered immediately following exposure to paintings. Contrary
      to our prediction, the behavioral data demonstrated that compared to realistic
      oil landscape paintings, exposure to traditional Chinese landscape paintings had
      no effect on performance on the flanker task. However, the neural data
      demonstrated an interaction effect such that there was greater activation in the
      inferior parietal cortex and the superior frontal gyrus on incongruent compared
      with congruent flanker trials when participants switched from viewing traditional
      Chinese landscape paintings to the flanker task than when they switched from
      realistic oil landscape paintings. These results suggest that switching from
      traditional Chinese landscape paintings placed greater demands on the brain's
      attention and working memory networks during the flanker task than did switching
      from realistic oil landscape paintings. 

PMID- 25610387
TI  - Memory load modulates graded changes in distracter filtering.
AB  - Our ability to maintain small amounts of information in mind is critical for
      successful performance on a wide range of tasks. However, it remains unclear
      exactly how this maintenance is achieved. One possibility is that it is brought
      about using mechanisms that overlap with those used for attentional control. That
      is, the same mechanisms that we use to regulate and optimize our sensory
      processing may be recruited when we maintain information in visual short-term
      memory (VSTM). We aimed to test this hypothesis by exploring how distracter
      filtering is modified by concurrent VSTM load. We presented participants with
      sequences of target items, the order and location of which had to be maintained
      in VSTM. We also presented distracter items alongside the targets, and these
      distracters were graded such that they could be either very similar or dissimilar
      to the targets. We analyzed scalp potentials using a novel multiple regression
      approach, which enabled us to explore the neural mechanisms by which the
      participants accommodated these variable distracters on a trial-to-trial basis.
      Critically, the effect of distracter filtering interacted with VSTM load; the
      same graded changes in perceptual similarity exerted effects of a different
      magnitude depending upon how many items participants were already maintaining in
      VSTM. These data provide compelling evidence that maintaining information in VSTM
      recruits an overlapping set of attentional control mechanisms that are otherwise
      used for distracter filtering. 

PMID- 25610388
TI  - Diffusion tensor imaging and white matter abnormalities in patients with
      disorders of consciousness.
AB  - Progress in neuroimaging has yielded new powerful tools which, potentially, can
      be applied to clinical populations, improve the diagnosis of neurological
      disorders and predict outcome. At present, the diagnosis of consciousness
      disorders is limited to subjective assessment and objective measurements of
      behavior, with an emerging role for neuroimaging techniques. In this review we
      focus on white matter alterations measured using Diffusion Tensor Imaging on
      patients with consciousness disorders, examining the most common diffusion
      imaging acquisition protocols and considering the main issues related to
      diffusion imaging analyses. We conclude by considering some of the remaining
      challenges to overcome, the existing knowledge gaps and the potential role of
      neuroimaging in understanding the pathogenesis and clinical features of disorders
      of consciousness. 

PMID- 25610389
TI  - Eye Movement Desensitization and Reprocessing (EMDR) re-examined as cognitive and
      emotional neuroentrainment.

PMID- 25610390
TI  - Near-infrared spectroscopy (NIRS) neurofeedback as a treatment for children with
      attention deficit hyperactivity disorder (ADHD)-a pilot study.
AB  - In this pilot study near-infrared spectroscopy (NIRS) neurofeedback was
      investigated as a new method for the treatment of Attention Deficit
      /Hyperactivity Disorder (ADHD). Oxygenated hemoglobin in the prefrontal cortex of
      children with ADHD was measured and fed back. 12 sessions of NIRS-neurofeedback
      were compared to the intermediate outcome after 12 sessions of EEG-neurofeedback
      (slow cortical potentials, SCP) and 12 sessions of EMG-feedback (muscular
      activity of left and right musculus supraspinatus). The task was either to
      increase or decrease hemodynamic activity in the prefrontal cortex (NIRS), to
      produce positive or negative shifts of SCP (EEG) or to increase or decrease
      muscular activity (EMG). In each group nine children with ADHD, aged 7-10 years,
      took part. Changes in parents' ratings of ADHD symptoms were assessed before and
      after the 12 sessions and compared within and between groups. For the NIRS-group
      additional teachers' ratings of ADHD symptoms, parents' and teachers' ratings of
      associated behavioral symptoms, childrens' self reports on quality of life and a
      computer based attention task were conducted before, 4 weeks and 6 months after
      training. As primary outcome, ADHD symptoms decreased significantly 4 weeks and 6
      months after the NIRS training, according to parents' ratings. In teachers'
      ratings of ADHD symptoms there was a significant reduction 4 weeks after the
      training. The performance in the computer based attention test improved
      significantly. Within-group comparisons after 12 sessions of NIRS-, EEG- and EMG
      training revealed a significant reduction in ADHD symptoms in the NIRS-group and
      a trend for EEG- and EMG-groups. No significant differences for symptom reduction
      were found between the groups. Despite the limitations of small groups and the
      comparison of a completed with two uncompleted interventions, the results of this
      pilot study are promising. NIRS-neurofeedback could be a time-effective treatment
      for ADHD and an interesting new option to consider in the treatment of ADHD. 

PMID- 25610391
TI  - Are movement disorders and sensorimotor injuries pathologic synergies? When
      normal multi-joint movement synergies become pathologic.
AB  - The intact nervous system has an exquisite ability to modulate the activity of
      multiple muscles acting at one or more joints to produce an enormous range of
      actions. Seemingly simple tasks, such as reaching for an object or walking, in
      fact rely on very complex spatial and temporal patterns of muscle activations.
      Neurological disorders such as stroke and focal dystonia affect the ability to
      coordinate multi-joint movements. This article reviews the state of the art of
      research of muscle synergies in the intact and damaged nervous system, their
      implications for recovery and rehabilitation, and proposes avenues for research
      aimed at restoring the nervous system's ability to control movement. 

PMID- 25610392
TI  - Correlated activity supports efficient cortical processing.
AB  - Visual recognition is a computational challenge that is thought to occur via
      efficient coding. An important concept is sparseness, a measure of coding
      efficiency. The prevailing view is that sparseness supports efficiency by
      minimizing redundancy and correlations in spiking populations. Yet, we recently
      reported that "choristers", neurons that behave more similarly (have correlated
      stimulus preferences and spontaneous coincident spiking), carry more
      generalizable object information than uncorrelated neurons ("soloists") in
      macaque inferior temporal (IT) cortex. The rarity of choristers (as low as 6% of
      IT neurons) indicates that they were likely missed in previous studies. Here, we
      report that correlation strength is distinct from sparseness (choristers are not
      simply broadly tuned neurons), that choristers are located in non-granular output
      layers, and that correlated activity predicts human visual search efficiency.
      These counterintuitive results suggest that a redundant correlational structure
      supports efficient processing and behavior. 

PMID- 25610393
TI  - The Decoding Toolbox (TDT): a versatile software package for multivariate
      analyses of functional imaging data.
AB  - The multivariate analysis of brain signals has recently sparked a great amount of
      interest, yet accessible and versatile tools to carry out decoding analyses are
      scarce. Here we introduce The Decoding Toolbox (TDT) which represents a user
      friendly, powerful and flexible package for multivariate analysis of functional
      brain imaging data. TDT is written in Matlab and equipped with an interface to
      the widely used brain data analysis package SPM. The toolbox allows running fast
      whole-brain analyses, region-of-interest analyses and searchlight analyses, using
      machine learning classifiers, pattern correlation analysis, or representational
      similarity analysis. It offers automatic creation and visualization of diverse
      cross-validation schemes, feature scaling, nested parameter selection, a variety
      of feature selection methods, multiclass capabilities, and pattern reconstruction
      from classifier weights. While basic users can implement a generic analysis in
      one line of code, advanced users can extend the toolbox to their needs or exploit
      the structure to combine it with external high-performance classification
      toolboxes. The toolbox comes with an example data set which can be used to try
      out the various analysis methods. Taken together, TDT offers a promising option
      for researchers who want to employ multivariate analyses of brain activity
      patterns. 

PMID- 25610394
TI  - Dissecting mechanisms of brain aging by studying the intrinsic excitability of
      neurons.
AB  - Several studies using vertebrate and invertebrate animal models have shown aging
      associated changes in brain function. Importantly, changes in soma size, loss or
      regression of dendrites and dendritic spines and alterations in the expression of
      neurotransmitter receptors in specific neurons were described. Despite this
      understanding, how aging impacts intrinsic properties of individual neurons or
      circuits that govern a defined behavior is yet to be determined. Here we discuss
      current understanding of specific electrophysiological changes in individual
      neurons and circuits during aging. 

PMID- 25610395
TI  - Complex regulation of gamma-secretase: from obligatory to modulatory subunits.
AB  - gamma-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves
      amyloid precursor protein (APP), catalyzing the formation of amyloid beta (Abeta)
      peptides that form amyloid plaques, which contribute to Alzheimer's disease (AD)
      pathogenesis. gamma-Secretase also cleaves Notch, among many other type I
      transmembrane substrates. Despite its seemingly promiscuous enzymatic capacity,
      gamma-secretase activity is tightly regulated. This regulation is a function of
      many cellular entities, including but not limited to the essential gamma
      secretase subunits, nonessential (modulatory) subunits, and gamma-secretase
      substrates. Regulation is also accomplished by an array of cellular events, such
      as presenilin (active subunit of gamma-secretase) endoproteolysis and hypoxia. In
      this review we discuss how gamma-secretase is regulated with the hope that an
      advanced understanding of these mechanisms will aid in the development of
      effective therapeutics for gamma-secretase-associated diseases like AD and Notch
      addicted cancer. 

PMID- 25610396
TI  - Immunological considerations in in utero hematopoetic stem cell transplantation
      (IUHCT).
AB  - In utero hematopoietic stem cell transplantation (IUHCT) is an attractive
      approach and a potentially curative surgery for several congenital hematopoietic
      diseases. In practice, this application has succeeded only in the context of
      Severe Combined Immunodeficiency Disorders. Here, we review potential
      immunological hurdles for the long-term establishment of chimerism and discuss
      relevant models and findings from both postnatal hematopoietic stem cell
      transplantation and IUHCT. 

PMID- 25610397
TI  - Effects of heme oxygenase-1 on innate and adaptive immune responses promoting
      pregnancy success and allograft tolerance.
AB  - The heme-degrading enzyme heme oxygenase-1 (HO-1) has cytoprotective,
      antioxidant, and anti-inflammatory properties. Moreover, HO-1 is reportedly
      involved in suppressing destructive immune responses associated with
      inflammation, autoimmune diseases, and allograft rejection. During pregnancy,
      maternal tolerance to foreign fetal antigens is a prerequisite for successful
      embryo implantation and fetal development. Here, HO-1 has been implicated in
      counteracting the overwhelming inflammatory immune responses towards fetal allo
      antigens, thereby contributing to fetal acceptance. Accordingly, HO-1 ablation
      negatively impacts the critical steps of pregnancy such as fertilization,
      implantation, placentation, and fetal growth. In the present review, we summarize
      recent data on the immune modulatory capacity of HO-1 towards allo-antigens
      expressed by the semi-allogeneic fetus and organ allografts. In this regard, HO-1
      has been shown to promote alloantigen tolerance by blocking dendritic cell
      maturation resulting in reduced T cell responses and increased numbers of
      regulatory T cells. Moreover, HO-1 is suggested to shift the uterine cytokine
      milieu towards a protective Th2 profile and protects fetal tissue from apoptosis
      by upregulating anti-apoptotic molecules. Thus, HO-1 is not only a pivotal
      regulator of the initial steps of pregnancy; but also, an important player in
      supporting the maternal immune system in tolerating the fetus. 

PMID- 25610399
TI  - Detecting cardiac contractile activity in the early mouse embryo using multiple
      modalities.
AB  - The heart is one of the first organs to develop during mammalian embryogenesis.
      In the mouse, it starts to form shortly after gastrulation, and is derived
      primarily from embryonic mesoderm. The embryonic heart is unique in having to
      perform a mechanical contractile function while undergoing complex morphogenetic
      remodeling. Approaches to imaging the morphogenesis and contractile activity of
      the developing heart are important in understanding not only how this remodeling
      is controlled but also the origin of congenital heart defects (CHDs). Here, we
      describe approaches for visualizing contractile activity in the developing mouse
      embryo, using brightfield time lapse microscopy and confocal microscopy of
      calcium transients. We describe an algorithm for enhancing this image data and
      quantifying contractile activity from it. Finally we describe how atomic force
      microscopy can be used to record contractile activity prior to it being
      microscopically visible. 

PMID- 25610398
TI  - Fluorescent knock-in mice to decipher the physiopathological role of G protein
      coupled receptors.
AB  - G protein-coupled receptors (GPCRs) modulate most physiological functions but are
      also critically involved in numerous pathological states. Approximately a third
      of marketed drugs target GPCRs, which places this family of receptors in the main
      arena of pharmacological pre-clinical and clinical research. The complexity of
      GPCR function demands comprehensive appraisal in native environment to collect in
      depth knowledge of receptor physiopathological roles and assess the potential of
      therapeutic molecules. Identifying neurons expressing endogenous GPCRs is
      therefore essential to locate them within functional circuits whereas GPCR
      visualization with subcellular resolution is required to get insight into agonist
      induced trafficking. Both remain frequently poorly investigated because direct
      visualization of endogenous receptors is often hampered by the lack of
      appropriate tools. Also, monitoring intracellular trafficking requires real-time
      visualization to gather in-depth knowledge. In this context, knock-in mice
      expressing a fluorescent protein or a fluorescent version of a GPCR under the
      control of the endogenous promoter not only help to decipher neuroanatomical
      circuits but also enable real-time monitoring with subcellular resolution thus
      providing invaluable information on their trafficking in response to a
      physiological or a pharmacological challenge. This review will present the animal
      models and discuss their contribution to the understanding of the
      physiopathological role of GPCRs. We will also address the drawbacks associated
      with this methodological approach and browse future directions. 

PMID- 25610401
TI  - Does impaired O2 delivery during exercise accentuate central and peripheral
      fatigue in patients with coexistent COPD-CHF?
AB  - Impairment in oxygen (O2) delivery to the central nervous system ("brain") and
      skeletal locomotor muscle during exercise has been associated with central and
      peripheral neuromuscular fatigue in healthy humans. From a clinical perspective,
      impaired tissue O2 transport is a key pathophysiological mechanism shared by
      cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD)
      and chronic heart failure (CHF). In addition to arterial hypoxemic conditions in
      COPD, there is growing evidence that cerebral and muscle blood flow and
      oxygenation can be reduced during exercise in both isolated COPD and CHF.
      Compromised cardiac output due to impaired cardiopulmonary function/interactions
      and blood flow redistribution to the overloaded respiratory muscles (i.e., ?work
      of breathing) may underpin these abnormalities. Unfortunately, COPD and CHF
      coexist in almost a third of elderly patients making these mechanisms potentially
      more relevant to exercise intolerance. In this context, it remains unknown
      whether decreased O2 delivery accentuates neuromuscular manifestations of central
      and peripheral fatigue in coexistent COPD-CHF. If this holds true, it is
      conceivable that delivering a low-density gas mixture (heliox) through non
      invasive positive pressure ventilation could ameliorate cardiopulmonary
      function/interactions and reduce the work of breathing during exercise in these
      patients. The major consequence would be increased O2 delivery to the brain and
      active muscles with potential benefits to exercise capacity (i.e., ?central and
      peripheral neuromuscular fatigue, respectively). We therefore hypothesize that
      patients with coexistent COPD-CHF stop exercising prematurely due to impaired
      central motor drive and muscle contractility as the cardiorespiratory system
      fails to deliver sufficient O2 to simultaneously attend the metabolic demands of
      the brain and the active limb muscles. 

PMID- 25610400
TI  - Cellular cardiac electrophysiology modeling with Chaste and CellML.
AB  - Chaste is an open-source C++ library for computational biology that has well
      developed cardiac electrophysiology tissue simulation support. In this paper, we
      introduce the features available for performing cardiac electrophysiology action
      potential simulations using a wide range of models from the Physiome repository.
      The mathematics of the models are described in CellML, with units for all
      quantities. The primary idea is that the model is defined in one place (the
      CellML file), and all model code is auto-generated at compile or run time; it
      never has to be manually edited. We use ontological annotation to identify model
      variables describing certain biological quantities (membrane voltage,
      capacitance, etc.) to allow us to import any relevant CellML models into the
      Chaste framework in consistent units and to interact with them via consistent
      interfaces. This approach provides a great deal of flexibility for analysing
      different models of the same system. Chaste provides a wide choice of numerical
      methods for solving the ordinary differential equations that describe the models.
      Fixed-timestep explicit and implicit solvers are provided, as discussed in
      previous work. Here we introduce the Rush-Larsen and Generalized Rush-Larsen
      integration techniques, made available via symbolic manipulation of the model
      equations, which are automatically rearranged into the forms required by these
      approaches. We have also integrated the CVODE solvers, a 'gold standard' for
      stiff systems, and we have developed support for symbolic computation of the
      Jacobian matrix, yielding further increases in the performance and accuracy of
      CVODE. We discuss some of the technical details of this work and compare the
      performance of the available numerical methods. Finally, we discuss how this is
      generalized in our functional curation framework, which uses a domain-specific
      language for defining complex experiments as a basis for comparison of model
      behavior. 

PMID- 25610402
TI  - Validating the Children's Sleep Habits Questionnaire Against Polysomnography and
      Actigraphy in School-Aged Children.
AB  - Sleep is a vital physiological behavior in children's development, and as such it
      is important to be able to efficiently and accurately assess whether children
      display difficulties with sleep quality and quantity. The Children's Sleep Habits
      Questionnaire [CSHQ; (1)] is one of the most commonly used assessment tools for
      pediatric sleep. However, this instrument has never been validated against the
      gold standard of sleep measurement [i.e., polysomnography (PSG)], and studies
      comparing it to actigraphy are limited. Therefore, the current study assessed the
      validity of four subscales of the CSHQ via direct comparison with PSG and
      actigraphy for 30 typically developing school-aged children (ages 6-12). No
      significant correlations between relevant CSHQ subscales and PSG variables were
      found. In terms of the actigraphy variables, only the CSHQ Night Wakings subscale
      achieved significance. In addition, sensitivity and specificity analyses revealed
      consistently low sensitivity and high specificity. Overall, the CSHQ Sleep Onset
      Delay, Sleep Duration, Night Wakings, and Sleep Disordered Breathing subscales
      showed low construct validity and diagnostic validity. These results underscore
      that caution should be taken when using the CSHQ as the sole screening tool for
      sleep problems in children. 

PMID- 25610403
TI  - Preserved Learning during the Symbol-Digit Substitution Test in Patients with
      Schizophrenia, Age-Matched Controls, and Elderly.
AB  - OBJECTIVE: Speed of processing, one of the main cognitive deficits in
      schizophrenia is most frequently measured with a digit-symbol-coding test.
      Performance on this test is additionally affected by writing speed and the rate
      at which symbol-digit relationships are learned, two factors that may be impaired
      in schizophrenia. This study aims to investigate the effects of sensorimotor
      speed, short-term learning, and long-term learning on task performance in
      schizophrenia. In addition, the study aims to explore differences in learning
      effects between patients with schizophrenia and elderly individuals. METHODS:
      Patients with schizophrenia (N = 30) were compared with age-matched healthy
      controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol-Digit
      Substitution Test (SDST). The task was administered on a digitizing tablet,
      allowing precise measurements of the time taken to write each digit (writing
      time) and the time to decode symbols into their corresponding digits (matching
      time). The SDST was administered on three separate days (day 1, day 2, day 7).
      Symbol-digit repetitions during the task represented short-term learning and
      repeating the task on different days represented long-term learning. RESULTS: The
      repetition of the same symbol-digit combinations within one test and the
      repetition of the test over days resulted in significant decreases in matching
      time. Interestingly, these short-term and long-term learning effects were about
      equal among the three groups. Individual participants showed a large variation in
      the rate of short-term learning. In general, patients with schizophrenia had the
      longest matching time whereas the elderly had the longest writing time. Writing
      time remained the same over repeated testing. CONCLUSION: The rate of learning
      and sensorimotor speed was found to have a substantial influence on the SDST
      score. However, a large individual variation in learning rate should be taken
      into account in the interpretation of task scores for processing speed. Equal
      learning rates among the three groups suggest that unintentional learning in
      schizophrenia and in the elderly is preserved. These findings are important for
      the design of rehabilitation programs for schizophrenia.

PMID- 25610404
TI  - A role for mental imagery in the experience and reduction of food cravings.

PMID- 25610405
TI  - Circadian clock proteins in mood regulation.
AB  - Mood regulation is known to be affected by the change of seasons. Recent research
      findings have suggested that mood regulation may be influenced by the function of
      circadian clocks. In addition, the activity of brown adipocytes has been
      hypothesized to contribute to mood regulation. Here, the overarching link to mood
      disorders might be the circadian clock protein nuclear receptor subfamily 1,
      group D, member 1. 

PMID- 25610406
TI  - Shared vision and autonomous motivation vs. financial incentives driving success
      in corporate acquisitions.
AB  - Successful corporate acquisitions require its managers to achieve substantial
      performance improvements in order to sufficiently cover acquisition premiums, the
      expected return of debt and equity investors, and the additional resources needed
      to capture synergies and accelerate growth. Acquirers understand that achieving
      the performance improvements necessary to cover these costs and create value for
      investors will most likely require a significant effort from mergers and
      acquisitions (M&A) management teams. This understanding drives the common and
      longstanding practice of offering hefty performance incentive packages to key
      managers, assuming that financial incentives will induce in-role and extra-role
      behaviors that drive organizational change and growth. The present study debunks
      the assumptions of this common M&A practice, providing quantitative evidence that
      shared vision and autonomous motivation are far more effective drivers of
      managerial performance than financial incentives. 

PMID- 25610407
TI  - Depression, not PTSD, is associated with attentional biases for emotional visual
      cues in early traumatized individuals with PTSD.
AB  - Using variants of the emotional Stroop task (EST), a large number of studies
      demonstrated attentional biases in individuals with PTSD across different types
      of trauma. However, the specificity and robustness of the emotional Stroop effect
      in PTSD have been questioned recently. In particular, the paradigm cannot
      disentangle underlying cognitive mechanisms. Transgenerational studies provide
      evidence that consequences of trauma are not limited to the traumatized people,
      but extend to close relatives, especially the children. To further investigate
      attentional biases in PTSD and to shed light on the underlying cognitive
      mechanism(s), a spatial-cueing paradigm with pictures of different emotional
      valence (neutral, anxiety, depression, trauma) was administered to individuals
      displaced as children during World War II (WWII) with (n = 22) and without PTSD
      (n = 26) as well as to non-traumatized controls (n = 22). To assess whether
      parental PTSD is associated with biased information processing in children, each
      one adult offspring was also included in the study. PTSD was not associated with
      attentional biases for trauma-related stimuli. There was no evidence for a
      transgenerational transmission of biased information processing. However, when
      samples were regrouped based on current depression, a reduced inhibition of
      return (IOR) effect emerged for depression-related cues. IOR refers to the
      phenomenon that with longer intervals between cue and target the validity effect
      is reversed: uncued locations are associated with shorter and cued locations with
      longer RTs. The results diverge from EST studies and demonstrate that findings on
      attentional biases yield equivocal results across different paradigms.
      Attentional biases for trauma-related material may only appear for verbal but not
      for visual stimuli in an elderly population with childhood trauma with PTSD.
      Future studies should more closely investigate whether findings from younger
      trauma populations also manifest in older trauma survivors. 

PMID- 25610408
TI  - Personality and well-being in adolescents.
AB  - Different profiles of the character dimensions of self-directedness,
      cooperativeness and self-transcendence result in different levels of wellbeing
      among adults. However, the influence of the multidimensional character profiles
      on adolescents' composite wellbeing remains unexplored. This study builds on
      previous studies with adults, and examines the linear and non-linear associations
      between the dimensions of the psychobiological model of personality and well
      being in adolescents. Participated in this study 1540 adolescents (M = 15.44, SD
      = 1.731). Personality was assessed using the Temperament and Character Inventory
      (TCI). Well-being was evaluated in a composite perspective: satisfaction with
      social support, health-related quality of life, satisfaction with life and
      affect. Variable-centered and individual-centered analyses were performed. Self
      directedness was strongly associated with all dimensions of affective and
      cognitive well-being regardless of the other two character traits.
      Cooperativeness was associated with non-affective well-being and with positive
      affect, but only when associated to elevation of Self-directedness and Self
      transcendence. Self-Directedness and Cooperativeness explained 15.5% of the non
      affective well-being variance. Self-Directedness and Self-Transcendence explained
      10.4% of the variance in affective well-being. This study confirms the tendencies
      found in previous studies with adults from other societies, where each character
      dimension gives an independent contribution to well-being depending on the
      interactions with other Character dimensions. Also, this study highlights the
      importance of considering the non-linear influences of the character dimensions
      in understanding of adolescents' wellbeing. These results have strong
      implications for youth positive mental health promotion, including for school
      based policies and practices. 

PMID- 25610409
TI  - Segmentation of dance movement: effects of expertise, visual familiarity, motor
      experience and music.
AB  - According to event segmentation theory, action perception depends on sensory cues
      and prior knowledge, and the segmentation of observed actions is crucial for
      understanding and memorizing these actions. While most activities in everyday
      life are characterized by external goals and interaction with objects or persons,
      this does not necessarily apply to dance-like actions. We investigated to what
      extent visual familiarity of the observed movement and accompanying music
      influence the segmentation of a dance phrase in dancers of different skill level
      and non-dancers. In Experiment 1, dancers and non-dancers repeatedly watched a
      video clip showing a dancer performing a choreographed dance phrase and indicated
      segment boundaries by key press. Dancers generally defined less segment
      boundaries than non-dancers, specifically in the first trials in which visual
      familiarity with the phrase was low. Music increased the number of segment
      boundaries in the non-dancers and decreased it in the dancers. The results
      suggest that dance expertise reduces the number of perceived segment boundaries
      in an observed dance phrase, and that the ways visual familiarity and music
      affect movement segmentation are modulated by dance expertise. In a second
      experiment, motor experience was added as factor, based on empirical evidence
      suggesting that action perception is modified by visual and motor expertise in
      different ways. In Experiment 2, the same task as in Experiment 1 was performed
      by dance amateurs, and was repeated by the same participants after they had
      learned to dance the presented dance phrase. Less segment boundaries were defined
      in the middle trials after participants had learned to dance the phrase, and
      music reduced the number of segment boundaries before learning. The results
      suggest that specific motor experience of the observed movement influences its
      perception and anticipation and makes segmentation broader, but not to the same
      degree as dance expertise on a professional level. 

PMID- 25610410
TI  - Differential changes in self-reported aspects of interoceptive awareness through
      3 months of contemplative training.
AB  - Interoceptive body awareness (IA) is crucial for psychological well-being and
      plays an important role in many contemplative traditions. However, until
      recently, standardized self-report measures of IA were scarce, not comprehensive,
      and the effects of interoceptive training on such measures were largely unknown.
      The Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire
      measures IA with eight different scales. In the current study, we investigated
      whether and how these different aspects of IA are influenced by a 3-months
      contemplative intervention in the context of the ReSource project, in which 148
      subjects engaged in daily practices of "Body Scan" and "Breath Meditation." We
      developed a German version of the MAIA and tested it in a large and diverse
      sample (n = 1,076). Internal consistencies were similar to the English version
      (0.56-0.89), retest reliability was high (rs: 0.66-0.79), and the MAIA showed
      good convergent and discriminant validity. Importantly, interoceptive training
      improved five out of eight aspects of IA, compared to a retest control group.
      Participants with low IA scores at baseline showed the biggest changes. Whereas
      practice duration only weakly predicted individual differences in change, self
      reported liking of the practices and degree of integration into daily life
      predicted changes on most scales. Interestingly, the magnitude of observed
      changes varied across scales. The strongest changes were observed for the
      regulatory aspects of IA, that is, how the body is used for self-regulation in
      daily life. No significant changes were observed for the Noticing aspect
      (becoming aware of bodily changes), which is the aspect that is predominantly
      assessed in other IA measures. This differential pattern underscores the
      importance to assess IA multi-dimensionally, particularly when interested in
      enhancement of IA through contemplative practice or other mind-body
      interventions. 

PMID- 25610412
TI  - Investment choice and perceived mating intentions regulated by external resource
      cues and internal fluctuation in blood glucose levels.
AB  - We examined resource allocation priorities in the framework of an updated Maslow
      hierarchy of fundamental human needs. In Experiment 1, the participants in the
      food abundance priming condition viewing photos of high-calorie food allocated
      more money to savings than to spending. However, the participants preferred
      spending to savings under the condition of mating availability priming with
      romantic photographs. In Experiment 2, before and after drinking either water or
      a sugary beverage, fasting participants rated photos of a conversation between a
      man and a woman. Water drinking lowered the rating scores of mating intentions as
      well as blood glucose (BG) levels. The sugary drink buffered this decline in
      sexual perceptivity. Overall, the change in BG levels was positively associated
      with changes in the ratings of mating intentions but was not associated with
      other likelihood ratings. These results suggest that both external cues of food
      and mating resources and internal BG fluctuation regulate the cognitive priority
      of physiological needs vs. mate acquisition and retention. 

PMID- 25610411
TI  - The endocannabinoid system: directing eating behavior and macronutrient
      metabolism.
AB  - For many years, the brain has been the primary focus for research on eating
      behavior. More recently, the discovery of the endocannabinoids (EC) and the
      endocannabinoid system (ECS), as well as the characterization of its actions on
      appetite and metabolism, has provided greater insight on the brain and food
      intake. The purpose of this review is to explain the actions of EC in the brain
      and other organs as well as their precursor polyunsaturated fatty acids (PUFA)
      that are converted to these endogenous ligands. The binding of the EC to the
      cannabinoid receptors in the brain stimulates food intake, and the ECS
      participates in systemic macronutrient metabolism where the gastrointestinal
      system, liver, muscle, and adipose are involved. The EC are biosynthesized from
      two distinct families of dietary PUFA, namely the n-6 and n-3. Based on their
      biochemistry, these PUFA are well known to exert considerable physiological and
      health-promoting actions. However, little is known about how these different
      families of PUFA compete as precursor ligands of cannabinoid receptors to
      stimulate appetite or perhaps down-regulate the ECS to amend food intake and
      prevent or control obesity. The goal of this review is to assess the current
      available research on ECS and food intake, suggest research that may improve the
      complications associated with obesity and diabetes by dietary PUFA intervention,
      and further reveal mechanisms to elucidate the relationships between substrate
      for EC synthesis, ligand actions on receptors, and the physiological consequences
      of the ECS. Dietary PUFA are lifestyle factors that could potentially curb eating
      behavior, which may translate to changes in macronutrient metabolism,
      systemically and in muscle, benefiting health overall. 

PMID- 25610413
TI  - Preschoolers show less trust in physically disabled or obese informants.
AB  - This research examined whether preschool-aged children show less trust in
      physically disabled or obese informants. In Study 1, when learning about novel
      physical activities and facts, 4- and 5-year-olds preferred to endorse the
      testimony of a physically abled, non-obese informant rather than a physically
      disabled or obese one. In Study 2, after seeing that the physically disabled or
      obese informant was previously reliable whereas the physically abled, non-obese
      one was unreliable, 4- and 5-year-olds did not show a significant preference for
      either informant. We conclude that in line with the literature on children's
      negative stereotypes of physically disabled or obese others, preschoolers are
      biased against these individuals as potential sources of new knowledge. This bias
      is robust in that past reliability might undermine its effect on children, but
      cannot reverse it. 

PMID- 25610414
TI  - Cognition and norms: toward a developmental account of moral agency in social
      dilemmas.
AB  - Most recent developments in the study of social dilemmas give an increasing
      amount of attention to cognition, belief systems, valuations, and language.
      However, developments in this field operate almost entirely under epistemological
      assumptions which only recognize the instrumental form of rationality and deny
      that "value judgments" or "moral questions" have cognitive content. This
      standpoint erodes the moral aspect of the choice situation and obstructs
      acknowledgment of the links connecting cognition, inner growth, and moral
      reasoning, and the significance of such links in reaching cooperative solutions
      to many social dilemmas. Concurrently, this standpoint places the role of
      communication and mutual understanding in promoting cooperation in morally
      relevant conflicts of action in a rather mysterious situation. This paper draws
      on Habermas's critique of instrumental action, and on the most recent
      developments in institutional and behavioral economics with a view to enhancing
      our knowledge of the interventions used to cope with social dilemmas. We conclude
      the paper with a brief presentation of a research strategy for examining the
      capacity of alternative developmental models to predict dissimilar choices under
      similar incentive conditions in social dilemmas. 

PMID- 25610415
TI  - The Child Affective Facial Expression (CAFE) set: validity and reliability from
      untrained adults.
AB  - Emotional development is one of the largest and most productive areas of
      psychological research. For decades, researchers have been fascinated by how
      humans respond to, detect, and interpret emotional facial expressions. Much of
      the research in this area has relied on controlled stimulus sets of adults posing
      various facial expressions. Here we introduce a new stimulus set of emotional
      facial expressions into the domain of research on emotional development-The Child
      Affective Facial Expression set (CAFE). The CAFE set features photographs of a
      racially and ethnically diverse group of 2- to 8-year-old children posing for six
      emotional facial expressions-angry, fearful, sad, happy, surprised, and disgusted
      and a neutral face. In the current work, we describe the set and report validity
      and reliability data on the set from 100 untrained adult participants. 

PMID- 25610416
TI  - SMART-ER: a Situation Model of Anticipated Response consequences in Tactical
      decisions in skill acquisition - Extended and Revised.
AB  - Situation Model of Anticipated Response consequences in tactical decisions
      (SMART) describes the interaction of top-down and bottom-up processes in skill
      acquisition and thus the dynamic interaction of sensory and motor capacities in
      embodied cognition. The empirically validated, extended, and revised SMART-ER can
      now predict when specific dynamic interactions of top-down and bottom-up
      processes have a beneficial or detrimental effect on performance and learning
      depending on situational constraints. The model is empirically supported and
      proposes learning strategies for when situation complexity varies or time
      pressure is present. Experiments from expertise research in sports illustrate
      that neither bottom-up nor top-down processes are bad or good per se but their
      effects depend on personal and situational characteristics. 

PMID- 25610417
TI  - Memory and comprehension deficits in spatial descriptions of children with non
      verbal and reading disabilities.
AB  - The present study investigated the difficulties encountered by children with non
      verbal learning disability (NLD) and reading disability (RD) when processing
      spatial information derived from descriptions, based on the assumption that both
      groups should find it more difficult than matched controls, but for different
      reasons, i.e., due to a memory encoding difficulty in cases of RD and to spatial
      information comprehension problems in cases of NLD. Spatial descriptions from
      both survey and route perspectives were presented to 9-12-year-old children
      divided into three groups: NLD (N = 12); RD (N = 12), and typically developing
      controls (TD; N = 15); then participants completed a sentence verification task
      and a memory for locations task. The sentence verification task was presented in
      two conditions: in one the children could refer to the text while answering the
      questions (i.e., text present condition), and in the other the text was withdrawn
      (i.e., text absent condition). Results showed that the RD group benefited from
      the text present condition, but was impaired to the same extent as the NLD group
      in the text absent condition, suggesting that the NLD children's difficulty is
      due mainly to their poor comprehension of spatial descriptions, while the RD
      children's difficulty is due more to a memory encoding problem. These results are
      discussed in terms of their implications in the neuropsychological profiles of
      children with NLD or RD, and the processes involved in spatial descriptions. 

PMID- 25610418
TI  - Unrecognized ambiguities in validity of intervention research: an example on
      explicit phonics and text-centered teaching.

PMID- 25610419
TI  - Applying how adults rehearse to understand how rehearsal may develop.

PMID- 25610420
TI  - Effects of script similarity on bilingual advantages in executive control are
      likely to be negligible or null.

PMID- 25610421
TI  - Effects of reducing the number of candidate tasks in voluntary task switching.
AB  - Recently, Demanet and Liefooghe (2014; Experiment 3) reported an experiment on
      voluntary task switching (VTS) in which the number of candidate tasks to choose
      from was reduced from 4 to 2 before participants indicated their task choice.
      This procedure was intended to prevent participants from choosing a task in
      advance of the presentation of a prompt to do so. This procedure is highly
      similar to a procedure recently employed by Kleinsorge and Scheil (2013) in a
      study of cued task switching which yielded evidence for a selective facilitation
      of task switches by a reduction of the number of tasks to two. In order to
      examine whether a similar effect would also be observed with VTS, we conceptually
      replicated the experiment of Demanet and Liefooghe (2014) with an additional
      control condition in which the number of tasks was not reduced. In this
      experiment, no evidence for a facilitation of task switching could be observed,
      pointing to a functional divergence between explicit task cues and the internally
      generated cues involved in VTS. In addition, we observed evidence for a selective
      advantage of forced switch trials over repetition-possible trials that was
      largely independent of the duration of the preparation interval. This effect was
      accompanied by a massive increase of task indication times in conditions with a
      reduced number of tasks, suggesting that this manipulation resulted in a
      pronounced change in the way participants performed voluntary task switches. 

PMID- 25610422
TI  - Central Integration of Canal and Otolith Signals is Abnormal in Vestibular
      Migraine: A Commentary.

PMID- 25610423
TI  - Early intervention to improve hand function in hemiplegic cerebral palsy.
AB  - Children with hemiplegic cerebral palsy often have marked hand involvement with
      excessive thumb adduction and flexion and limited active wrist extension from
      infancy. Post-lesional aberrant plasticity can lead to progressive abnormalities
      of the developing motor system. Disturbances of somatosensory and visual function
      and developmental disregard contribute to difficulties with hand use. Progressive
      soft tissue and bony changes may occur, leading to contractures, which further
      limit function in a vicious cycle. Early intervention might help to break this
      cycle, however, the precise nature and appropriateness of the intervention must
      be carefully considered. Traditional approaches to the hemiplegic upper limb
      include medications and botulinum toxin injections to manage abnormalities of
      tone, and surgical interventions. Therapist input, including provision of
      orthoses, remains a mainstay although many therapies have not been well
      evaluated. There has been a recent increase in interventions for the hemiplegic
      upper limb, mostly aimed outside the period of infancy. These include trials of
      constraint-induced movement therapy (CIMT) and bimanual therapy as well as the
      use of virtual reality and robot-assisted therapy. In future, non-invasive brain
      stimulation may be combined with therapy. Interventions under investigation in
      the infant age group include modified CIMT and action observation therapy. A
      further approach which may be suited to the infant with thumb-in-palm deformity,
      but which requires evaluation, is the use of elastic taping. Enhanced cutaneous
      feedback through mechanical stimulation to the skin provided by the tape during
      movement has been postulated to modulate ongoing muscle activity. If effective,
      this would represent a low-cost, safe, widely applicable early intervention. 

PMID- 25610426
TI  - Corrigendum: biased signaling of protease-activated receptors.

PMID- 25610425
TI  - Farnesol-like endogenous sesquiterpenoids in vertebrates: the probable but
      overlooked functional "inbrome" anti-aging counterpart of juvenile hormone of
      insects?
AB  - Literature on the question whether the juvenile stage of vertebrates is
      hormonally regulated is scarce. It seems to be intuitively assumed that this
      stage of development is automated, and does not require any specific hormone(s).
      Such reasoning mimics the state of affairs in insects until it was shown that
      surgical removal of a tiny pair of glands in the head, the corpora allata, ended
      larval life and initiated metamorphosis. Decades later, the responsible hormone
      was found and named "juvenile hormone" (JH) because when present, it makes a
      larva molt into another larval stage. JH is a simple ester of farnesol, a
      sesquiterpenoid present in all eukaryotes. Whereas vertebrates do not have an
      anatomical counterpart of the corpora allata, their tissues do contain farnesol
      like sesquiterpenoids (FLS). Some display typical JH activity when tested in
      appropriate insect bioassays. Some FLS are intermediates in the biosynthetic
      pathway of cholesterol, a compound that insects and nematodes (=Ecdysozoa) cannot
      synthesize by themselves. They ingest it as a vitamin. Until a recent (2014)
      reexamination of the basic principle underlying insect metamorphosis, it had been
      completely overlooked that the Ca(2+)-pump (SERCA) blocker thapsigargin is a
      sesquiterpenoid that mimics the absence of JH in inducing apoptosis. In our
      opinion, being in the juvenile state is primarily controlled by endogenous FLS
      that participate in controlling the activity of Ca(2+)-ATPases in the
      sarco(endo)plasmic reticulum (SERCAs), not only in insects but in all eukaryotes.
      Understanding the control mechanisms of being in the juvenile state may boost
      research not only in developmental biology in general, but also in diseases that
      develop after the juvenile stage, e.g., Alzheimer's disease. It may also help to
      better understand some of the causes of obesity, a syndrome that holometabolous
      last larval insects severely suffer from, and for which they found a very drastic
      but efficient solution, namely metamorphosis. 

PMID- 25610424
TI  - Interaction between Vestibular Compensation Mechanisms and Vestibular
      Rehabilitation Therapy: 10 Recommendations for Optimal Functional Recovery.
AB  - This review questions the relationships between the plastic events responsible
      for the recovery of vestibular function after a unilateral vestibular loss
      (vestibular compensation), which has been well described in animal models in the
      last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more
      empirical basis for vestibular loss patients. The main objective is not to
      propose a catalog of results but to provide clinicians with an understandable
      view on when and how to perform VR therapy, and why VR may benefit from basic
      knowledge and may influence the recovery process. With this perspective, 10 major
      recommendations are proposed as ways to identify an optimal functional recovery.
      Among them are the crucial role of active and early VR therapy, coincidental with
      a post-lesion sensitive period for neuronal network remodeling, the instructive
      role that VR therapy may play in this functional reorganization, the need for
      progression in the VR therapy protocol, which is based mainly on adaptation
      processes, the necessity to take into account the sensorimotor, cognitive, and
      emotional profile of the patient to propose individual or "a la carte" VR
      therapies, and the importance of motivational and ecologic contexts. More than 10
      general principles are very likely, but these principles seem crucial for the
      fast recovery of vestibular loss patients to ensure good quality of life. 

PMID- 25610427
TI  - Health Outcomes in Acromegaly: Depression and Anxiety are Promising Targets for
      Improving Reduced Quality of Life.
AB  - INTRODUCTION: Remission criteria of acromegaly are based on biochemical
      variables, i.e., normalization of increased hormone levels. However, the
      established reduction in Quality of Life (QoL) is suggested to be independent of
      biochemical control. The aim of this study was to test which aspects predict QoL
      best in acromegaly. METHODS/DESIGN: This is a prospective cohort study in 80
      acromegalic patients, with a cross-sectional and longitudinal part. The main
      outcome measure was health-related QoL, measured by a generic and a disease
      specific questionnaire (the SF-36 and AcroQoL). Main predictors were age, gender,
      biochemical control, disease characteristics, treatment modalities, and
      psychopathology. RESULTS: Our cohort of 80 acromegalics had a mean age 54.7 +/-
      12.3 years with an average disease duration of 10.8 +/- 10.0 years. Ratio macro
      /microadenoma was 54/26. In adjusted mixed method models, we found that
      psychopathology significantly predicts QoL in acromegaly (in models including the
      variables age, gender, disease duration, tumor size, basal hormone levels,
      relevant treatment modalities, and relevant comorbidities), with a higher degree
      of psychopathology indicating a lower QoL (depression vs. AcroQoL: B = -1.175, p
      < 0.001, depression vs. SF-36: B = -1.648, p < 0.001, anxiety vs. AcroQoL: B = 
      0.399, p < 0.001, anxiety vs. SF-36: B = -0.661, p < 0.001). The explained
      variances demonstrate superiority of psychopathology over biochemical control and
      other variables in predicting QoL in our models. DISCUSSION: Superiority of
      psychopathology over biochemical control calls for a more extensive approach
      regarding diagnosing depression and anxiety in pituitary adenomas to improve QoL.
      Depressive symptoms and anxiety are modifiable factors that might provide
      valuable targets for possible future treatment interventions.

PMID- 25610428
TI  - Impact of Maternal Melatonin Suppression on Amount and Functionality of Brown
      Adipose Tissue (BAT) in the Newborn Sheep.
AB  - In human and sheep newborns, brown adipose tissue (BAT) accrued during fetal
      development is used for newborn thermogenesis. Here, we explored the role of
      maternal melatonin during gestation on the amount and functionality of BAT in the
      neonate. We studied BAT from six lambs gestated by ewes exposed to constant light
      from 63% gestation until delivery to suppress melatonin (LL), six lambs gestated
      by ewes exposed to LL but receiving daily oral melatonin (12 mg at 1700 h, LL +
      Mel) and another six control lambs gestated by ewes maintained in 12 h light:12 h
      dark (LD). Lambs were instrumented at 2 days of age. At 4-6 days of age, they
      were exposed to 24 degrees C (thermal neutrality conditions) for 1 h, 4 degrees C
      for 1 h, and 24 degrees C for 1 h. Afterward, lambs were euthanized and BAT was
      dissected for mRNA measurement, histology, and ex vivo experiments. LL newborns
      had lower central BAT and skin temperature under thermal neutrality and at 4
      degrees C, and higher plasma norepinephrine concentration than LD newborns. In
      response to 4 degrees C, they had a pronounced decrease in skin temperature and
      did not increase plasma glycerol. BAT weight in LL newborns was about half of
      that of LD newborns. Ex vivo, BAT from LL newborns showed increased basal
      lipolysis and did not respond to NE. In addition, expression of
      adipogenic/thermogenic genes (UCP1, ADBR3, PPARgamma, PPARalpha, PGC1alpha,
      C/EBPbeta, and perilipin) and of the clock genes Bmal1, Clock, and Per2 was
      increased. Remarkably, the effects observed in LL newborns were absent in LL +
      Mel newborns. Thus, our results support that maternal melatonin during gestation
      is important in determining amount and normal functionality of BAT in the
      neonate. 

PMID- 25610429
TI  - Characterization of the genetic environment of bla ESBL genes, integrons and
      toxin-antitoxin systems identified on large transferrable plasmids in multi-drug
      resistant Escherichia coli.
AB  - OBJECTIVES: Previously 14 conjugative plasmids from multi-drug resistant (MDR)
      Escherichia coli from healthy humans and food-producing animals in Switzerland
      were sequenced. The aim of this study was to extend the genetic characterization
      of these plasmids with a focus on bla ESBL genes including bla CTX-M-1 and bla
      TEM, class 1 integrons and toxin-antitoxin (TA) systems contained therein.
      METHODS: The nucleotide sequences and subsequent annotation therein of 14
      conjugative plasmids were previously determined from their corresponding
      transconjugants. The TA loci were confirmed by RASTA-Bacteria. RESULTS: Eight of
      the conjugative plasmids identified were found to encode genes expressing ESBLs.
      Structural heterogeneity was noted in the regions flanking both the bla CTX-M-1
      and bla TEM genes. The bla CTX-M-1 genes were associated with the common
      insertion sequences ISEcp1 and IS26, and uniquely with an IS5 element in one
      case; while bla TEM genes were found to be associated with IS26 and Tn2. A new
      bla TEM-210 gene was identified. Seven class 1 integrons were also identified and
      assigned into 3 groups, denoted as In54, In369 and In501. Sixteen TA loci
      belonging to 4 of the TA gene families (relBE, vapBC, ccd and mazEF) were
      identified on 11 of these plasmids. CONCLUSIONS: Comparative sequence analysis of
      these plasmids provided data on the structures likely to contribute to sequence
      diversity associated with these accessory genes, including IS26, ISEcp1 and Tn2.
      All of them contribute to the dissemination of the corresponding resistance genes
      located on the different plasmids. There appears to be no association between
      beta-lactam encoding genes and TA systems.

PMID- 25610431
TI  - Finding and identifying the viral needle in the metagenomic haystack: trends and
      challenges.
AB  - Collectively, viruses have the greatest genetic diversity on Earth, occupy
      extremely varied niches and are likely able to infect all living organisms. Viral
      infections are an important issue for human health and cause considerable
      economic losses when agriculturally important crops or husbandry animals are
      infected. The advent of metagenomics has provided a precious tool to study
      viruses by sampling them in natural environments and identifying the genomic
      composition of a sample. However, reaching a clear recognition and taxonomic
      assignment of the identified viruses has been hampered by the computational
      difficulty of these problems. In this perspective paper we examine the trends in
      current research for the identification of viral sequences in a metagenomic
      sample, pinpoint the intrinsic computational difficulties for the identification
      of novel viral sequences within metagenomic samples, and suggest possible avenues
      to overcome them. 

PMID- 25610430
TI  - oriC-encoded instructions for the initiation of bacterial chromosome replication.
AB  - Replication of the bacterial chromosome initiates at a single origin of
      replication that is called oriC. This occurs via the concerted action of numerous
      proteins, including DnaA, which acts as an initiator. The origin sequences vary
      across species, but all bacterial oriCs contain the information necessary to
      guide assembly of the DnaA protein complex at oriC, triggering the unwinding of
      DNA and the beginning of replication. The requisite information is encoded in the
      unique arrangement of specific sequences called DnaA boxes, which form a
      framework for DnaA binding and assembly. Other crucial sequences of bacterial
      origin include DNA unwinding element (DUE, which designates the site at which
      oriC melts under the influence of DnaA) and binding sites for additional proteins
      that positively or negatively regulate the initiation process. In this review, we
      summarize our current knowledge and understanding of the information encoded in
      bacterial origins of chromosomal replication, particularly in the context of
      replication initiation and its regulation. We show that oriC encoded instructions
      allow not only for initiation but also for precise regulation of replication
      initiation and coordination of chromosomal replication with the cell cycle (also
      in response to environmental signals). We focus on Escherichia coli, and then
      expand our discussion to include several other microorganisms in which additional
      regulatory proteins have been recently shown to be involved in coordinating
      replication initiation to other cellular processes (e.g., Bacillus, Caulobacter,
      Helicobacter, Mycobacterium, and Streptomyces). We discuss diversity of bacterial
      oriC regions with the main focus on roles of individual DNA recognition sequences
      at oriC in binding the initiator and regulatory proteins as well as the overall
      impact of these proteins on the formation of initiation complex. 

PMID- 25610433
TI  - Genetic basis of the association of resistance genes mef(I) (macrolides) and catQ
      (chloramphenicol) in streptococci.
AB  - In streptococci mef(I) and catQ, two relatively uncommon macrolide and
      chloramphenicol resistance genes, respectively, are typically linked in a genetic
      module designated IQ module. Though variable, the module consistently
      encompasses, and is sometimes reduced to, a conserved ~5.8-kb mef(I)-catQ
      fragment. The prototype IQ module was described in Streptococcus pneumoniae. IQ
      like modules have subsequently been detected in Streptococcus pyogenes and in
      different species of viridans group streptococci, where mef(E) may be found
      instead of mef(I). Three genetic elements, one carrying the prototype IQ module
      from S. pneumoniae and two carrying different, defective IQ modules from S.
      pyogenes, have recently been characterized. All are integrative and conjugative
      elements (ICEs) belonging to the Tn5253 family, and have been designated
      ICESpn529IQ, ICESpy029IQ and ICESpy005IQ, respectively. ICESpy029IQ and
      ICESpy005IQ were the first Tn5253 family ICEs to be described in S. pyogenes. A
      wealth of new information has been obtained by comparing their genetic
      organization, chromosomal integration, and transferability. The origin of the IQ
      module is unknown. The mechanism by which it spreads in streptococci is
      discussed. 

PMID- 25610434
TI  - Adaptive laboratory evolution of Escherichia coli K-12 MG1655 for growth at high
      hydrostatic pressure.
AB  - Much of microbial life on Earth grows and reproduces under the elevated
      hydrostatic pressure conditions that exist in deep-ocean and deep-subsurface
      environments. In this study adaptive laboratory evolution (ALE) experiments were
      conducted to investigate the possible modification of the piezosensitive
      Escherichia coli for improved growth at high pressure. After approximately 500
      generations of selection, a strain was isolated that acquired the ability to grow
      at pressure non-permissive for the parental strain. Remarkably, this strain
      displayed growth properties and changes in the proportion and regulation of
      unsaturated fatty acids that indicated the acquisition of multiple piezotolerant
      properties. These changes developed concomitantly with a change in the gene
      encoding the acyl carrier protein, which is required for fatty acid synthesis. 

PMID- 25610432
TI  - Evolution of small prokaryotic genomes.
AB  - As revealed by genome sequencing, the biology of prokaryotes with reduced genomes
      is strikingly diverse. These include free-living prokaryotes with ~800 genes as
      well as endosymbiotic bacteria with as few as ~140 genes. Comparative genomics is
      revealing the evolutionary mechanisms that led to these small genomes. In the
      case of free-living prokaryotes, natural selection directly favored genome
      reduction, while in the case of endosymbiotic prokaryotes neutral processes
      played a more prominent role. However, new experimental data suggest that
      selective processes may be at operation as well for endosymbiotic prokaryotes at
      least during the first stages of genome reduction. Endosymbiotic prokaryotes have
      evolved diverse strategies for living with reduced gene sets inside a host
      defined medium. These include utilization of host-encoded functions (some of them
      coded by genes acquired by gene transfer from the endosymbiont and/or other
      bacteria); metabolic complementation between co-symbionts; and forming
      consortiums with other bacteria within the host. Recent genome sequencing
      projects of intracellular mutualistic bacteria showed that previously believed
      universal evolutionary trends like reduced G+C content and conservation of genome
      synteny are not always present in highly reduced genomes. Finally, the simplified
      molecular machinery of some of these organisms with small genomes may be used to
      aid in the design of artificial minimal cells. Here we review recent genomic
      discoveries of the biology of prokaryotes endowed with small gene sets and
      discuss the evolutionary mechanisms that have been proposed to explain their
      peculiar nature. 

PMID- 25610435
TI  - Functional genomics of corrinoid starvation in the organohalide-respiring
      bacterium Dehalobacter restrictus strain PER-K23.
AB  - De novo corrinoid biosynthesis represents one of the most complicated metabolic
      pathways in nature. Organohalide-respiring bacteria (OHRB) have developed
      different strategies to deal with their need of corrinoid, as it is an essential
      cofactor of reductive dehalogenases, the key enzymes in OHR metabolism. In
      contrast to Dehalococcoides mccartyi, the genome of Dehalobacter restrictus
      strain PER-K23 contains a complete set of corrinoid biosynthetic genes, of which
      cbiH appears to be truncated and therefore non-functional, possibly explaining
      the corrinoid auxotrophy of this obligate OHRB. Comparative genomics within
      Dehalobacter spp. revealed that one (operon-2) of the five distinct corrinoid
      biosynthesis associated operons present in the genome of D. restrictus appeared
      to be present only in that particular strain, which encodes multiple members of
      corrinoid transporters and salvaging enzymes. Operon-2 was highly up-regulated
      upon corrinoid starvation both at the transcriptional (346-fold) and proteomic
      level (46-fold on average), in line with the presence of an upstream cobalamin
      riboswitch. Together, these data highlight the importance of this operon in
      corrinoid homeostasis in D. restrictus and the augmented salvaging strategy this
      bacterium adopted to cope with the need for this essential cofactor. 

PMID- 25610436
TI  - Factors that mediate and prevent degradation of the inactive and unstable GudB
      protein in Bacillus subtilis.
AB  - The Gram-positive model bacterium Bacillus subtilis contains two glutamate
      dehydro genase-encoding genes, rocG and gudB. While the rocG gene encodes the
      functional GDH, the gudB gene is cryptic (gudB(CR) ) in the laboratory strain 168
      due to a perfect 18 bp-long direct repeat that renders the GudB enzyme inactive
      and unstable. Although constitutively expressed the GudB(CR) protein can hardly
      be detected in B. subtilis as it is rapidly degraded within stationary growth
      phase. Its high instability qualifies GudB(CR) as a model substrate for studying
      protein turnover in B. subtilis. Recently, we have developed a visual screen to
      monitor the GudB(CR) stability in the cell using a GFP-GudB(CR) fusion. Using
      fluorescent microscopy we found that the GFP protein is simultaneously degraded
      together with GudB(CR). This allows us to analyze the stability of GudB(CR) in
      living cells. By combining the visual screen with a transposon mutagenesis
      approach we looked for mutants that show an increased fluorescence signal
      compared to the wild type indicating a stabilized GFP-GudB(CR) fusion. We
      observed, that disruption of the arginine kinase encoding gene mcsB upon
      transposon insertion leads to increased amounts of the GFP-GudB(CR) fusion in
      this mutant. Deletion of the cognate arginine phosphatase YwlE in contrast
      results in reduced levels of the GFP-GudB(CR) fusion. Recently, it was shown that
      the kinase McsB is involved in phosphorylation of GudB(CR) on arginine residues.
      Here we show that selected arginine-lysine point mutations of GudB(CR) exhibit no
      influence on degradation. The activity of McsB and YwlE, however, are crucial for
      the activation and inhibition, respectively, of a proteolytic machinery that
      efficiently degrades the unstable GudB(CR) protein in B. subtilis. 

PMID- 25610437
TI  - Post-translational modification of P II signal transduction proteins.
AB  - The PII proteins constitute one of the most widely distributed families of signal
      transduction proteins in nature. They are pivotal players in the control of
      nitrogen metabolism in bacteria and archaea, and are also found in the plastids
      of plants. Quite remarkably PII proteins control the activities of a diverse
      range of enzymes, transcription factors and membrane transport proteins, and in
      all known cases they achieve their regulatory effect by direct interaction with
      their target. PII proteins in the Proteobacteria and the Actinobacteria are
      subject to post-translational modification by uridylylation or adenylylation
      respectively, whilst in some Cyanobacteria they can be modified by
      phosphorylation. In all these cases the protein's modification state is
      influenced by the cellular nitrogen status and is thought to regulate its
      activity. However, in many organisms there is no evidence for modification of PII
      proteins and indeed the ability of these proteins to respond to the cellular
      nitrogen status is fundamentally independent of post-translational modification.
      In this review we explore the role of post-translational modification in PII
      proteins in the light of recent studies. 

PMID- 25610438
TI  - From immunomonitoring to immune intervention.

PMID- 25610439
TI  - Platelets in inflammation: regulation of leukocyte activities and vascular
      repair.
AB  - There is now a large body of evidence that platelets are central actors of
      inflammatory reactions. Indeed, platelets play a significant role in a variety of
      inflammatory diseases. These diseases include conditions as varied as
      atherosclerosis, arthritis, dermatitis, glomerulonephritis, or acute lung injury.
      In this context, one can note that inflammation is a convenient but imprecise
      catch-all term that is used to cover a wide range of situations. Therefore, when
      discussing the role of platelets in inflammation, it is important to clearly
      define the pathophysiological context and the exact stage of the reaction.
      Inflammatory reactions are indeed multistep processes that can be either acute or
      chronic, and their sequence can vary greatly depending on the situation and organ
      concerned. Here, we focus on how platelets contribute to inflammatory reactions
      involving recruitment of neutrophils and/or macrophages. Specifically, we review
      past and recent data showing that platelets intervene at various stages of these
      reactions to regulate parameters such as endothelial permeability, the
      recruitment of neutrophils and macrophages and their effector functions, as well
      as inflammatory bleeding. The mechanisms underlying these various modulating
      effect of platelets are also discussed. 

PMID- 25610440
TI  - Innate immune programing by endotoxin and its pathological consequences.
AB  - Monocytes and macrophages play pivotal roles in inflammation and homeostasis.
      Recent studies suggest that dynamic programing of macrophages and monocytes may
      give rise to distinct "memory" states. Lipopolysaccharide (LPS), a classical
      pattern recognition molecule, dynamically programs innate immune responses.
      Emerging studies have revealed complex dynamics of cellular responses to LPS,
      with high doses causing acute, resolving inflammation, while lower doses are
      associated with low-grade and chronic non-resolving inflammation. These phenomena
      hint at dynamic complexities of intra-cellular signaling circuits downstream of
      the Toll-like receptor 4 (TLR4). In this review, we examine pathological effects
      of varying LPS doses with respect to the dynamics of innate immune responses and
      key molecular regulatory circuits responsible for these effects. 

PMID- 25610443
TI  - A simple framework to analyze water constraints on seasonal transpiration in
      rubber tree (Hevea brasiliensis) plantations.
AB  - Climate change and fast extension in climatically suboptimal areas threaten the
      sustainability of rubber tree cultivation. A simple framework based on reduction
      factors of potential transpiration was tested to evaluate the water constraints
      on seasonal transpiration in tropical sub-humid climates, according pedoclimatic
      conditions. We selected a representative, mature stand in a drought-prone area.
      Tree transpiration, evaporative demand and soil water availability were measured
      every day over 15 months. The results showed that basic relationships with
      evaporative demand, leaf area index and soil water availability were globally
      supported. However, the implementation of a regulation of transpiration at high
      evaporative demand whatever soil water availability was necessary to avoid large
      overestimates of transpiration. The details of regulation were confirmed by the
      analysis of canopy conductance response to vapor pressure deficit. The final
      objective of providing hierarchy between the main regulation factors of seasonal
      and annual transpiration was achieved. In the tested environmental conditions,
      the impact of atmospheric drought appeared larger importance than soil drought
      contrary to expectations. Our results support the interest in simple models to
      provide a first diagnosis of water constraints on transpiration with limited
      data, and to help decision making toward more sustainable rubber plantations. 

PMID- 25610441
TI  - CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response
      to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T
      Cells in Pathogenesis.
AB  - HIV-1 infection results in chronic activation of cells in lymphoid tissue,
      including T cells, B-cells, and myeloid lineage cells. The resulting
      characteristic hyperplasia is an amalgam of proliferating host immune cells in
      the adaptive response, increased concentrations of innate response mediators due
      to viral and bacterial products, and homeostatic responses to inflammation. While
      it is generally thought that CD4 T cells are greatly depleted, in fact, two types
      of CD4 T cells appear to be increased, namely, regulatory T cells (Tregs) and T
      follicular helper cells (Tfh). These cells have opposing roles, but may both be
      important in the pathogenic process. Whether Tregs are failing in their role to
      limit lymphocyte activation is unclear, but there is no doubt now that Tfh are
      associated with B-cell hyperplasia and increased germinal center activity.
      Antiretroviral therapy may reduce the lymphocyte activation, but not completely,
      and therefore, there is a need for interventions that selectively enhance normal
      CD4 function without exacerbating Tfh, B-cell, or Treg dysfunction. 

PMID- 25610444
TI  - Cr-resistant rhizo- and endophytic bacteria associated with Prosopis juliflora
      and their potential as phytoremediation enhancing agents in metal-degraded soils.
AB  - Prosopis juliflora is characterized by distinct and profuse growth even in
      nutritionally poor soil and environmentally stressed conditions and is believed
      to harbor some novel heavy metal-resistant bacteria in the rhizosphere and
      endosphere. This study was performed to isolate and characterize Cr-resistant
      bacteria from the rhizosphere and endosphere of P. juliflora growing on the
      tannery effluent contaminated soil. A total of 5 and 21 bacterial strains were
      isolated from the rhizosphere and endosphere, respectively, and were shown to
      tolerate Cr up to 3000 mg l(-1). These isolates also exhibited tolerance to other
      toxic heavy metals such as, Cd, Cu, Pb, and Zn, and high concentration (174 g l(
      1)) of NaCl. Moreover, most of the isolated bacterial strains showed one or more
      plant growth-promoting activities. The phylogenetic analysis of the 16S rRNA gene
      showed that the predominant species included Bacillus, Staphylococcus and
      Aerococcus. As far as we know, this is the first report analyzing rhizo- and
      endophytic bacterial communities associated with P. juliflora growing on the
      tannery effluent contaminated soil. The inoculation of three isolates to ryegrass
      (Lolium multiflorum L.) improved plant growth and heavy metal removal from the
      tannery effluent contaminated soil suggesting that these bacteria could enhance
      the establishment of the plant in contaminated soil and also improve the
      efficiency of phytoremediation of heavy metal-degraded soils. 

PMID- 25610442
TI  - Agrobacterium: nature's genetic engineer.
AB  - Agrobacterium was identified as the agent causing the plant tumor, crown gall
      over 100 years ago. Since then, studies have resulted in many surprising
      observations. Armin Braun demonstrated that Agrobacterium infected cells had
      unusual nutritional properties, and that the bacterium was necessary to start the
      infection but not for continued tumor development. He developed the concept of a
      tumor inducing principle (TIP), the factor that actually caused the disease.
      Thirty years later the TIP was shown to be a piece of a tumor inducing (Ti)
      plasmid excised by an endonuclease. In the next 20 years, most of the key
      features of the disease were described. The single-strand DNA (T-DNA) with the
      endonuclease attached is transferred through a type IV secretion system into the
      host cell where it is likely coated and protected from nucleases by a bacterial
      secreted protein to form the T-complex. A nuclear localization signal in the
      endonuclease guides the transferred strand (T-strand), into the nucleus where it
      is integrated randomly into the host chromosome. Other secreted proteins likely
      aid in uncoating the T-complex. The T-DNA encodes enzymes of auxin, cytokinin,
      and opine synthesis, the latter a food source for Agrobacterium. The genes
      associated with T-strand formation and transfer (vir) map to the Ti plasmid and
      are only expressed when the bacteria are in close association with a plant. Plant
      signals are recognized by a two-component regulatory system which activates vir
      genes. Chromosomal genes with pleiotropic functions also play important roles in
      plant transformation. The data now explain Braun's old observations and also
      explain why Agrobacterium is nature's genetic engineer. Any DNA inserted between
      the border sequences which define the T-DNA will be transferred and integrated
      into host cells. Thus, Agrobacterium has become the major vector in plant genetic
      engineering. 

PMID- 25610445
TI  - Identification and characterization of histone deacetylases in tomato (Solanum
      lycopersicum).
AB  - Histone acetylation and deacetylation at the N-terminus of histone tails play
      crucial roles in the regulation of eukaryotic gene activity. Histone acetylation
      and deacetylation are catalyzed by histone acetyltransferases and histone
      deacetylases (HDACs), respectively. A growing number of studies have demonstrated
      the importance of histone deacetylation/acetylation on genome stability,
      transcriptional regulation, development and response to stress in Arabidopsis.
      However, the biological functions of HDACs in tomato have not been investigated
      previously. Fifteen HDACs identified from tomato (Solanum lycopersicum) can be
      grouped into RPD3/HDA1, SIR2 and HD2 families based on phylogenetic analysis.
      Meanwhile, 10 members of the RPD3/HDA1 family can be further subdivided into four
      groups, namely Class I, Class II, Class III, and Class IV. High similarities of
      protein sequences and conserved domains were identified among SlHDACs and their
      homologs in Arabidopsis. Most SlHDACs were expressed in all tissues examined with
      different transcript abundance. Transient expression in Arabidopsis protoplasts
      showed that SlHDA8, SlHDA1, SlHDA5, SlSRT1 and members of the HD2 family were
      localized to the nucleus, whereas SlHDA3 and SlHDA4 were localized in both the
      cytoplasm and nucleus. The difference in the expression patterns and subcellular
      localization of SlHDACs suggest that they may play distinct functions in tomato.
      Furthermore, we found that three members of the RPD3/HDA1 family, SlHDA1, SIHDA3
      and SlHDA4, interacted with TAG1 (TOMATO AGAMOUS1) and TM29 (TOMATO MADS BOX29),
      two MADS-box proteins associated with tomato reproductive development, indicating
      that these HDACs may be involved in gene regulation in reproductive development. 

PMID- 25610446
TI  - A large-scale genetic screen for mutants with altered salicylic acid accumulation
      in Arabidopsis.
AB  - Salicylic acid (SA) is a key defense signal molecule against biotrophic and
      hemibiotrophic pathogens in plants, but how SA is synthesized in plant cells
      still remains elusive. Identification of new components involved in pathogen
      induced SA accumulation would help address this question. To this end, we
      performed a large-scale genetic screen for mutants with altered SA accumulation
      during pathogen infection in Arabidopsis using a bacterial biosensor
      Acinetobacter sp. ADPWH_lux-based SA quantification method. A total of 35,000 M2
      plants in the npr1-3 mutant background have been individually analyzed for the
      bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326-induced SA
      accumulation. Among the mutants isolated, 19 had SA levels lower than npr1 (sln)
      and two exhibited increased SA accumulation in npr1 (isn). Complementation tests
      revealed that seven of the sln mutants are new alleles of eds5/sid1, two are
      sid2/eds16 alleles, one is allelic to pad4, and the remaining seven sln and two
      isn mutants are new non-allelic SA accumulation mutants. Interestingly, a large
      group of mutants (in the npr1-3 background), in which Psm ES4326-induced SA
      levels were similar to those in the wild-type Columbia plants, were identified,
      suggesting that the signaling network fine-tuning pathogen-induced SA
      accumulation is complex. We further characterized the sln1 single mutant and
      found that Psm ES4326-induced defense responses were compromised in this mutant.
      These defense response defects could be rescued by exogenous SA, suggesting that
      SLN1 functions upstream of SA. The sln1 mutation was mapped to a region on the
      north arm of chromosome I, which contains no known genes regulating pathogen
      induced SA accumulation, indicating that SLN1 likely encodes a new regulator of
      SA biosynthesis. Thus, the new sln and isn mutants identified in this genetic
      screen are valuable for dissecting the molecular mechanisms underlying pathogen
      induced SA accumulation in plants. 

PMID- 25610447
TI  - Variation potential influence on photosynthetic cyclic electron flow in pea.
AB  - Cyclic electron flow is an important component of the total photosynthetic
      electron flow and participates in adaptation to the action of stressors. Local
      leaf stimulation induces electrical signals, including variation potential (VP),
      which inactivate photosynthesis; however, their influence on cyclic electron flow
      has not been investigated. The aim of this study was to investigate VP's
      influence on cyclic electron flow in pea (Pisum sativum L.). VP was induced in
      pea seedling leaves by local heating and measured in an adjacent, undamaged leaf
      by extracellular electrodes. CO2 assimilation was measured using a portable gas
      exchange measuring system. Photosystem I and II parameters were investigated
      using a measuring system for simultaneous assessment of P700 oxidation and
      chlorophyll fluorescence. Heating-induced VP reduced CO2 assimilation and
      electron flow through photosystem II. In response, cyclic electron flow rapidly
      decreased and subsequently slowly increased. Slow increases in cyclic flow were
      caused by decreased electron flow through photosystem II, which was mainly
      connected with VP-induced photosynthetic dark stage inactivation. However, direct
      influence by VP on photosystem I also participated in activation of cyclic
      electron flow. Thus, VP, induced by local leaf-heating, activated cyclic electron
      flow in undamaged leaves. This response was similar to photosynthetic changes
      observed under the direct action of stressors. Possible mechanisms of VP's
      influence on cyclic flow were discussed. 

PMID- 25610448
TI  - Chilling requirement of Ribes cultivars.
AB  - It is usually thought that adequate winter chill is required for the full
      flowering of many temperate woody species. This paper investigates the
      sensitivity of blackcurrant bud burst and flowering to natural weather
      fluctuations in a temperate maritime climate, and compares a range of chill
      models that have been proposed for assessing the accumulation of winter chill.
      Bud break for four contrasting cultivars are compared in an exceptionally cold
      and in a mild winter in Eastern Scotland. The results confirm the importance of
      chilling at temperatures lower than 0 degrees C and demonstrate that no single
      chilling function applies equally to all blackcurrant cultivars. There is a
      pressing need for further model development to take into account the relationship
      between chilling temperatures and warming temperatures occurring both during and
      after the chill accumulation period. 

PMID- 25610449
TI  - A high-density genetic map of cucumber derived from Specific Length Amplified
      Fragment sequencing (SLAF-seq).
AB  - High-density genetic map provides an essential framework for accurate and
      efficient genome assembly and QTL fine mapping. Construction of high-density
      genetic maps appears more feasible since the advent of next-generation sequencing
      (NGS), which eases SNP discovery and high-throughput genotyping of large
      population. In this research, a high-density genetic map of cucumber (Cucumis
      sativus L.) was successfully constructed across an F2 population by a recently
      developed Specific Length Amplified Fragment sequencing (SLAF-seq) method. In
      total, 18.69 GB of data containing 93,460,000 paired-end reads were obtained
      after preprocessing. The average sequencing depth was 44.92 in the D8 (female
      parent), 42.16 in the Jin5-508 (male parent), and 5.01 in each progeny. 79,092
      high-quality SLAFs were detected, of which 6784 SLAFs were polymorphic, and 1892
      of the polymorphic markers met the requirements for constructing genetic map. The
      genetic map spanned 845.87 cm with an average genetic distance of 0.45 cm. It is
      a reliable linkage map for fine mapping and molecular breeding of cucumber for
      its high marker density and well-ordered markers. 

PMID- 25610450
TI  - Cerato-platanin family proteins: one function for multiple biological roles?

PMID- 25610452
TI  - Circles within circles: commentary on Ghosal et al. (2013) "Circ2Traits: a
      comprehensive database for circular RNA potentially associated with disease and
      traits".

PMID- 25610453
TI  - Ischemic stroke detection system with a computer-aided diagnostic ability using
      an unsupervised feature perception enhancement method.
AB  - We propose an ischemic stroke detection system with a computer-aided diagnostic
      ability using a four-step unsupervised feature perception enhancement method. In
      the first step, known as preprocessing, we use a cubic curve contrast enhancement
      method to enhance image contrast. In the second step, we use a series of methods
      to extract the brain tissue image area identified during preprocessing. To detect
      abnormal regions in the brain images, we propose using an unsupervised region
      growing algorithm to segment the brain tissue area. The brain is centered on a
      horizontal line and the white matter of the brain's inner ring is split into
      eight regions. In the third step, we use a coinciding regional location method to
      find the hybrid area of locations where a stroke may have occurred in each
      cerebral hemisphere. Finally, we make corrections and mark the stroke area with
      red color. In the experiment, we tested the system on 90 computed tomography (CT)
      images from 26 patients, and, with the assistance of two radiologists, we proved
      that our proposed system has computer-aided diagnostic capabilities. Our results
      show an increased stroke diagnosis sensitivity of 83% in comparison to 31% when
      radiologists use conventional diagnostic images. 

PMID- 25610454
TI  - Combined prediction model of death toll for road traffic accidents based on
      independent and dependent variables.
AB  - In order to build a combined model which can meet the variation rule of death
      toll data for road traffic accidents and can reflect the influence of multiple
      factors on traffic accidents and improve prediction accuracy for accidents, the
      Verhulst model was built based on the number of death tolls for road traffic
      accidents in China from 2002 to 2011; and car ownership, population, GDP, highway
      freight volume, highway passenger transportation volume, and highway mileage were
      chosen as the factors to build the death toll multivariate linear regression
      model. Then the two models were combined to be a combined prediction model which
      has weight coefficient. Shapley value method was applied to calculate the weight
      coefficient by assessing contributions. Finally, the combined model was used to
      recalculate the number of death tolls from 2002 to 2011, and the combined model
      was compared with the Verhulst and multivariate linear regression models. The
      results showed that the new model could not only characterize the death toll data
      characteristics but also quantify the degree of influence to the death toll by
      each influencing factor and had high accuracy as well as strong practicability. 

PMID- 25610455
TI  - A study of driver's route choice behavior based on evolutionary game theory.
AB  - This paper proposes a route choice analytic method that embeds cumulative
      prospect theory in evolutionary game theory to analyze how the drivers adjust
      their route choice behaviors under the influence of the traffic information. A
      simulated network with two alternative routes and one variable message sign is
      built to illustrate the analytic method. We assume that the drivers in the
      transportation system are bounded rational, and the traffic information they
      receive is incomplete. An evolutionary game model is constructed to describe the
      evolutionary process of the drivers' route choice decision-making behaviors. Here
      we conclude that the traffic information plays an important role in the route
      choice behavior. The driver's route decision-making process develops towards
      different evolutionary stable states in accordance with different transportation
      situations. The analysis results also demonstrate that employing cumulative
      prospect theory and evolutionary game theory to study the driver's route choice
      behavior is effective. This analytic method provides an academic support and
      suggestion for the traffic guidance system, and may optimize the travel
      efficiency to a certain extent. 

PMID- 25610451
TI  - The evolution of nanopore sequencing.
AB  - The "$1000 Genome" project has been drawing increasing attention since its launch
      a decade ago. Nanopore sequencing, the third-generation, is believed to be one of
      the most promising sequencing technologies to reach four gold standards set for
      the "$1000 Genome" while the second-generation sequencing technologies are
      bringing about a revolution in life sciences, particularly in genome sequencing
      based personalized medicine. Both of protein and solid-state nanopores have been
      extensively investigated for a series of issues, from detection of ionic current
      blockage to field-effect-transistor (FET) sensors. A newly released protein
      nanopore sequencer has shown encouraging potential that nanopore sequencing will
      ultimately fulfill the gold standards. In this review, we address advances,
      challenges, and possible solutions of nanopore sequencing according to these
      standards. 

PMID- 25610456
TI  - Image superresolution reconstruction via granular computing clustering.
AB  - The problem of generating a superresolution (SR) image from a single low
      resolution (LR) input image is addressed via granular computing clustering in the
      paper. Firstly, and the training images are regarded as SR image and partitioned
      into some SR patches, which are resized into LS patches, the training set is
      composed of the SR patches and the corresponding LR patches. Secondly, the
      granular computing (GrC) clustering is proposed by the hypersphere representation
      of granule and the fuzzy inclusion measure compounded by the operation between
      two granules. Thirdly, the granule set (GS) including hypersphere granules with
      different granularities is induced by GrC and used to form the relation between
      the LR image and the SR image by lasso. Experimental results showed that GrC
      achieved the least root mean square errors between the reconstructed SR image and
      the original image compared with bicubic interpolation, sparse representation,
      and NNLasso. 

PMID- 25610457
TI  - Context transfer in reinforcement learning using action-value functions.
AB  - This paper discusses the notion of context transfer in reinforcement learning
      tasks. Context transfer, as defined in this paper, implies knowledge transfer
      between source and target tasks that share the same environment dynamics and
      reward function but have different states or action spaces. In other words, the
      agents learn the same task while using different sensors and actuators. This
      requires the existence of an underlying common Markov decision process (MDP) to
      which all the agents' MDPs can be mapped. This is formulated in terms of the
      notion of MDP homomorphism. The learning framework is Q-learning. To transfer the
      knowledge between these tasks, the feature space is used as a translator and is
      expressed as a partial mapping between the state-action spaces of different
      tasks. The Q-values learned during the learning process of the source tasks are
      mapped to the sets of Q-values for the target task. These transferred Q-values
      are merged together and used to initialize the learning process of the target
      task. An interval-based approach is used to represent and merge the knowledge of
      the source tasks. Empirical results show that the transferred initialization can
      be beneficial to the learning process of the target task. 

PMID- 25610458
TI  - Test generation algorithm for fault detection of analog circuits based on extreme
      learning machine.
AB  - This paper proposes a novel test generation algorithm based on extreme learning
      machine (ELM), and such algorithm is cost-effective and low-risk for analog
      device under test (DUT). This method uses test patterns derived from the test
      generation algorithm to stimulate DUT, and then samples output responses of the
      DUT for fault classification and detection. The novel ELM-based test generation
      algorithm proposed in this paper contains mainly three aspects of innovation.
      Firstly, this algorithm saves time efficiently by classifying response space with
      ELM. Secondly, this algorithm can avoid reduced test precision efficiently in
      case of reduction of the number of impulse-response samples. Thirdly, a new
      process of test signal generator and a test structure in test generation
      algorithm are presented, and both of them are very simple. Finally, the
      abovementioned improvement and functioning are confirmed in experiments. 

PMID- 25610459
TI  - A Multicenter Randomized Controlled Trial of Malignant Gastric Outlet
      Obstruction: Tailored Partially Covered Stents (Placed Fluoroscopically) versus
      Standard Uncovered Stents (Placed Endoscopically).
AB  - The aim of our study is to compare the efficacy and safety of "outlet-shape"
      tailored stents with standard stents for the management of distal gastric cancer
      causing gastric outlet obstructions (GOOs) with varying gastric cavity shapes and
      sizes. To determine the shape and size of the GOOs, stomach opacifications were
      performed using contrast media before stenting. Two basic shapes of the residual
      cavity of the proximal GOO were observed: cup shaped or approximately cup shaped
      and funnel shaped or approximately funnel shaped. Other shapes were not found. In
      the GOO tailored group, the size and shape of the proximal ends of the tailored
      stent were suited for the residual cavity of the proximal GOO. The tailored
      stents included large cup-shaped stents and large funnel-shaped stents. GOO
      tailored covered stents led to less restenosis and reintervention rates compared
      to standard uncovered stents but with the same survival. 

PMID- 25610460
TI  - Clinical outcome of patients with complete pathological response to neoadjuvant
      chemoradiotherapy for locally advanced rectal cancers: the Indian scenario.
AB  - Introduction. Neoadjuvant chemoradiotherapy and total mesorectal excision are
      considered the standard treatment for locally advanced rectal cancer. Various
      studies have reported pathological downstaging and a complete pathological
      response rate of 15%-27% following neoadjuvant chemoradiotherapy which has
      translated into improved survival. We endeavour to determine the clinical outcome
      of patients attaining a complete pathological tumor response following
      neoadjuvant chemoradiotherapy in the Indian setting where most of our patient
      population is younger and presents with aggressive tumor biology. Materials and
      Methods. Clinicopathological and treatment details were recorded for 64 patients
      achieving pathological complete response from 2010 to 2013. Disease-free survival
      (DFS), overall survival (OS), and locoregional and systemic recurrence rates were
      evaluated for these patients. Results. After a median follow-up of 30.5 months
      (range 11-59 months), the 3-year overall survival (OS) was 94.6% and the 3-year
      disease-free survival (DFS) was 88.5%. The locoregional and systemic recurrence
      rates were 4.7% and 3.1%, respectively. Conclusion. In the Indian subcontinent,
      despite younger patients with aggressive tumor biology, outcome in complete
      responders is good. 

PMID- 25610461
TI  - Risks of misinterpretation in the evaluation of the effect of fruit-based drinks
      in postprandial studies.
AB  - It has been suggested that some fruit-based drinks (FBD) may delay the onset of
      postprandial stress, which is involved in the pathogenesis of many diseases. The
      majority of the studies, which have investigated the effects of FBD on
      postprandial stress, involved a placebo that was a drink with the same content in
      sugars or carbohydrates of the FBD, but without the bioactive antioxidant
      compounds. These studies were aimed more at evaluating the effect of the
      antioxidants rather than the effect of the FBD as a whole. Only 4 studies
      compared the effect of FBD with water as control and did not support the
      hypothesis that FBD could inhibit postprandial dysmetabolism, as well as the
      studies that compared the effect of orange juice and cola. Overall, the results
      suggest a complex relationship between postprandial dysmetabolism, inflammation,
      and oxidative stress. Furthermore, the inflammatory and oxidative stress markers
      need further analytical validation and normal ranges should be established in
      order to reach a firm conclusion. Finally, caution should be taken in the
      interpretation of the effect of FBD in postprandial studies and the reviewed
      results suggest that dietary recommendations should aim to limit rather than
      increase sugar-sweetened beverages consumption. 

PMID- 25610462
TI  - A Computational Approach for Predicting Role of Human MicroRNAs in MERS-CoV
      Genome.
AB  - The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of
      human coronavirus called MERS-CoV which has global fatality rate of about 30%. We
      are investigating potential antiviral therapeutics against MERS-CoV by using host
      microRNAs (miRNAs) which may downregulate viral gene expression to quell viral
      replication. We computationally predicted potential 13 cellular miRNAs from 11
      potential hairpin sequences of MERS-CoV genome. Our study provided an interesting
      hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR
      4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR
      548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa
      miR-342-3p, would be antiviral therapeutics against MERS-CoV infection. 

PMID- 25610463
TI  - The Antiviral Effect of High-Molecular Weight Poly-Gamma-Glutamate against
      Newcastle Disease Virus on Murine Macrophage Cells.
AB  - This study demonstrates the capacity of HM-gamma-PGA treatment to significantly
      protect murine macrophage cells (RAW 264.7 cells) against NDV infection. Such
      protection can be explained by the induction of antiviral state of HM-gamma-PGA
      in RAW 264.7 cells via TLR4-mediated IRF-3, IRF-7, IFN-beta, and IFN-related gene
      induction as shown in time-dependent changes in mRNA expression confirmed by
      polymerase chain reaction (PCR). Moreover, the present research also showed that
      HM-gamma-PGA can induce proinflammatory cytokine secretion in RAW 264.7 as
      measured by enzyme-linked immunosorbent assay (ELISA). Therefore, our findings
      suggest that HM-gamma-PGA can be a potential antiviral substance that can inhibit
      NDV infection through its stimulation of antiviral state on RAW 264.7 cells.
      These results have been consistent with the previous studies showing that HM
      gamma-PGA can protect RAW 264.7 cells and mice against influenza infection.
      However, it should be noted that although murine macrophage cells are susceptible
      to NDV, they are not the natural host cells of the virus; thus further in vivo
      and in vitro studies involving chicken and chicken immune cells are needed to
      fully assess the efficacy and applicability of HM-gamma-PGA in the poultry
      industry. 

PMID- 25610464
TI  - Assessment of the Correlation between Appointment Scheduling and Patient
      Satisfaction in a Pediatric Dental Setup.
AB  - Introduction. The practice of modern pediatric dentistry requires delivery of
      quality care in combination with adherence to excellent business as well as time
      management principles. A definite appointment schedule should be presented to the
      parents on the first or second appointment. More importantly, the prescribed
      schedule should be followed to the best of the professional abilities of the
      pediatric dentist. Aims. The aim of the study was to assess the co-relation
      between appointment scheduling and patient satisfaction in a pediatric dental
      setup with the objective of understanding the parameters related to appointment
      scheduling to increase patient satisfaction. Method. A total of 40 patients, who
      visited the Department of Pediatric and Preventive Dentistry, YMT Dental College
      & Hospital, for dental treatment were selected on a random basis. A questionnaire
      with a set of 6 questions with a rating scale of 1-5 to assess the patient
      satisfaction related to appointment scheduling was prepared. Results. A
      significant number of the patients were happy with the existing appointment
      scheduling system barring a few exceptions. 

PMID- 25610465
TI  - A comparative evaluation of microleakage in class v composite restorations.
AB  - Aim. To compare and evaluate the microleakage in class V lesions restored with
      composite resin with and without liner and injectable nanohybrid composite resin.
      Materials and Methodology. 60 class V cavities were prepared in 30 freshly
      extracted teeth. After etching and application of bonding agents these cavities
      were divided into three groups: Group A (n = 20)-restored with composite resin,
      Group B (n = 20)-flowable composite resin liner + composite resin, and Group C (n
      = 20)-restored with injectable composite resin. After curing all the specimens
      were subjected to thermocycling and cyclic loading. Specimens were stained with
      0.5% basic fuchsin and evaluated for dye penetration. Results. Results are
      subjected to Kruskal Wallis and Wilcoxon test. Conclusion. Within the limitations
      of this study, none of the three materials were free from microleakage. All the
      three materials showed more microleakage at gingival margins compared to occlusal
      margins. Among all the groups G-aenial Flo showed the least microleakage at the
      gingival wall. 

PMID- 25610466
TI  - H. pylori May Not Be Associated with Iron Deficiency Anemia in Patients with
      Normal Gastrointestinal Tract Endoscopy Results.
AB  - Background. The aim of this study was to investigate the association between iron
      deficiency anemia and H. pylori in patients with normal gastrointestinal tract
      endoscopy results. Materials and Methods. A total of 117 male patients with
      normal gastrointestinal tract endoscopy results were included in this
      retrospective study. The study and control groups included 69 and 48 patients
      with and without iron deficiency anemia, respectively. The prevalence of H.
      pylori, the number of RBCs, and the levels of HGB, HTC, MCV, iron, and ferritin
      were calculated and compared. Results. There was no statistically significant
      difference found between the groups according to the prevalence of H. pylori
      (65.2% versus 64.6%, P = 0.896). Additionally, the levels of RBCs, HGB, HTC, MCV,
      iron, and ferritin in the patients in the study group were lower than those in
      the control group (P < 0.05). Finally, there was no association between iron
      deficiency anemia and H. pylori (OR 1.02, Cl 95% 0.47-2.22, and P = 0.943).
      Conclusion. H. pylori is not associated with iron deficiency anemia in male
      patients with normal gastrointestinal tract endoscopy results. 

PMID- 25610467
TI  - Childhood septicemia in Nepal: documenting the bacterial etiology and its
      susceptibility to antibiotics.
AB  - Introduction. Children are among the most vulnerable population groups to
      contract illnesses. The varying microbiological pattern of septicemia warrants
      the need for an ongoing review of the causative organisms and their antimicrobial
      susceptibility pattern. Therefore, the objective of this study was to document
      the bacterial etiology of childhood septicemia and its antibiotic susceptibility
      profile. Methods. Cross-sectional type of study in 1630 suspected patients was
      conducted at CMCTH from January 2012 to December 2013. Blood samples were
      collected aseptically for culture. The organisms grown were identified by
      standard microbiological methods recommended by American Society for Microbiology
      (ASM) and subjected to antibiotic susceptibility testing by modified Kirby-Bauer
      disk diffusion method. Methicillin resistance was confirmed using cefoxitin and
      oxacillin disks methods. Results. Septicemia was detected in 172 (10.6%) cases.
      Among Gram-positive organisms, coagulase negative staphylococci (CoNS) were
      leading pathogen and Acinetobacter spp. were leading pathogen among Gram-negative
      isolates. Vancomycin, teicoplanin, and clindamycin were the most effective
      antibiotics against Gram-positive isolates while amikacin was effective against
      Gram-positive as well as Gram-negative isolates. Methicillin resistance was
      detected in 44.4% of Staphylococcus aureus. Conclusions. This study has
      highlighted the burden of bacterial etiology for septicemia among children in a
      tertiary care center of central Nepal. 

PMID- 25610468
TI  - Comparison of Perinatal Outcome of Preterm Births Starting in Primary Care versus
      Secondary Care in Netherlands: A Retrospective Analysis of Nationwide Collected
      Data.
AB  - Introduction. In Netherlands, the obstetric care system is divided into primary
      and secondary care by risk level of the pregnancy. We assessed the incidence of
      preterm birth according to level of care and the association between level of
      care at time of labor onset and delivery and adverse perinatal outcome. Methods.
      Singleton pregnancies recorded in Netherlands Perinatal Registry between 1999 and
      2007, with spontaneous birth between 25(+0) and 36(+6) weeks, were included.
      Three groups were compared: (1) labor onset and delivery in primary care; (2)
      labor onset in primary care and delivery in secondary care; (3) labor onset and
      delivery in secondary care. Multivariable logistic regression analyses were
      performed to calculate the risk of perinatal mortality and Apgar score <=4.
      Results. Of all preterm deliveries, 42% had labor onset and 7.9% had also
      delivery in primary care. Women with labor onset between 34(+0) and 36(+6) weeks
      who were referred before delivery to secondary care had the lowest risk of
      perinatal mortality (aOR 0.49 (0.30-0.79)). Risk of perinatal mortality (aOR
      1.65; 95% CI 1.20-2.27) and low Apgar score (aOR 1.95; 95% CI 1.53-2.48) were
      significantly increased in preterm home delivery. Conclusion. Referral before
      delivery is associated with improved perinatal outcome in the occurrence of
      preterm labor onset in primary care. 

PMID- 25610469
TI  - Maintenance and neuronal differentiation of chicken induced pluripotent stem-like
      cells.
AB  - Pluripotent stem cells have the potential to become any cell in the adult body,
      including neurons and glia. Avian stem cells could be used to study questions,
      like vocal learning, that would be difficult to examine with traditional mouse
      models. Induced pluripotent stem cells (iPSCs) are differentiated cells that have
      been reprogrammed to a pluripotent stem cell state, usually using inducing genes
      or other molecules. We recently succeeded in generating avian iPSC-like cells
      using mammalian genes, overcoming a limitation in the generation and use of iPSCs
      in nonmammalian species (Rossello et al., 2013). However, there were no
      established optimal cell culture conditions for avian iPSCs to establish long
      term cell lines and thus to study neuronal differentiation in vitro. Here we
      present an efficient method of maintaining chicken iPSC-like cells and for
      differentiating them into action potential generating neurons. 

PMID- 25610470
TI  - Contribution of Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells to
      Chimeras through Injection and Coculture of Embryos.
AB  - Blastocyst injection and morula aggregation are commonly used to evaluate stem
      cell pluripotency based on chimeric contribution of the stem cells. To assess the
      protocols for generating chimeras from stem cells, 8-cell mouse embryos were
      either injected or cocultured with mouse embryonic stem cells and induced
      pluripotent stem cells, respectively. Although a significantly higher chimera
      rate resulted from blastocyst injection, the highest germline contribution
      resulted from injection of 8-cell embryos with embryonic stem cells. The fully
      agouti colored chimeras were generated from both injection and coculture of 8
      cell embryos with embryonic stem cells. Additionally, microsatellite DNA
      screening showed that the fully agouti colored chimeras were fully embryonic stem
      cell derived mice. Unlike embryonic stem cells, the mouse chimeras were only
      generated from injection of 8-cell embryos with induced pluripotent stem cells
      and none of these showed germline transmission. The results indicated that
      injection of 8-cell embryos is the most efficient method for assessing stem cell
      pluripotency and generating induced pluripotent stem cell chimeras, embryonic
      stem cell chimeras with germline transmission, and fully mouse embryonic stem
      cell derived mice. 

PMID- 25610471
TI  - Effects of toll-like receptors 3 and 4 in the osteogenesis of stem cells.
AB  - Objective. To investigate the effects of Toll-like receptors in stem cell
      osteogenesis. Methods. Bone marrow mesenchymal stem cells (BMSCs) were divided
      into the blank group, the TLR-3 activated group, and the TLR-4 activated group.
      After 10 days' osteogenic-promoting culture, expression of type I collagen and
      osteocalcin was determined by Western blot. Osteoblasts (OBs) were also divided
      into three groups mentioned above. Alkaline phosphatase (ALP) and alizarin red
      staining were performed after 10 days' ossification-inducing culture. The
      expression of beta-catenin was investigated by Western blot. Results. Both the
      TLR-3 and TLR-4 activated groups had increased expression of type I collagen and
      osteocalcin; the effect of TLR-4 was stronger. The intensity of alizarin red and
      ALP staining was strongest in the TLR-3 activated group and weakest in the TLR-4
      activated group. Activation of TLR-4 decreased the expression of beta-catenin,
      whilst activation of TLR-3 did not affect the expression of beta-catenin.
      Discussion. This study suggested that both TLR-3 and -4 promoted differentiation
      of BMSCs to OBs. TLR-3 had an inducing effect on the ossification of OBs to
      osteocytes, whilst the effect of TLR-4 was the opposite because of its inhibitory
      effect on the Wnt signaling pathway. 

PMID- 25610472
TI  - The Effects of Skin-to-Skin Contact on Temperature and Breastfeeding
      Successfulness in Full-Term Newborns after Cesarean Delivery.
AB  - Background. The skin-to-skin contact (SSC) of mother and newborn is uncommon full
      term newborns after delivering via cesarean section due to the possibility of
      hypothermia in the infants. The aim of this study was to compare mothers' and
      infant's temperatures after delivering via cesarean section. Material and
      Methods. In this randomized clinical trial, 90 infant/mothers dyads delivered via
      cesarean section were randomized to SSC (n = 46) and routine care (n = 44). In
      experimental group, skin-to-skin contact was performed for one hour and in the
      routine group the infant was dressed and put in the cot according to hospital
      routine care. The newborns' mothers' temperatures in both groups were taken at
      half-hour intervals. The data was analyzed using descriptive statistics, t-tests,
      and chi-square tests. Results. The means of the newborns' temperatures
      immediately after SSC (P = 0.86), half an hour (P = 0.31), and one hour (P =
      0.52) after the intervention did not show statistically significant differences
      between the two groups. The mean scores of the infants' breastfeeding assessment
      in SSC (8.76+/-3.63) and routine care (7.25+/-3.5) groups did not show
      significant differences (P = 0.048). Conclusion. Mother and infant's skin-to-skin
      contact is possible after delivering via cesarean section and does not increase
      the risk of hypothermia. 

PMID- 25610473
TI  - Qigong exercise alleviates fatigue, anxiety, and depressive symptoms, improves
      sleep quality, and shortens sleep latency in persons with chronic fatigue
      syndrome-like illness.
AB  - Objectives. To evaluate the effectiveness of Baduanjin Qigong exercise on sleep,
      fatigue, anxiety, and depressive symptoms in chronic fatigue syndrome- (CFS-)
      like illness and to determine the dose-response relationship. Methods. One
      hundred fifty participants with CFS-like illness (mean age = 39.0, SD = 7.9) were
      randomly assigned to Qigong and waitlist. Sixteen 1.5-hour Qigong lessons were
      arranged over 9 consecutive weeks. Pittsburgh Sleep Quality Index (PSQI), Chalder
      Fatigue Scale (ChFS), and Hospital Anxiety and Depression Scale (HADS) were
      assessed at baseline, immediate posttreatment, and 3-month posttreatment. The
      amount of Qigong self-practice was assessed by self-report. Results. Repeated
      measures analyses of covariance showed a marginally nonsignificant (P = 0.064)
      group by time interaction in the PSQI total score, but it was significant for the
      "subjective sleep quality" and "sleep latency" items, favoring Qigong exercise.
      Improvement in "subjective sleep quality" was maintained at 3-month
      posttreatment. Significant group by time interaction was also detected for the
      ChFS and HADS anxiety and depression scores. The number of Qigong lessons
      attended and the amount of Qigong self-practice were significantly associated
      with sleep, fatigue, anxiety, and depressive symptom improvement. Conclusion.
      Baduanjin Qigong was an efficacious and acceptable treatment for sleep
      disturbance in CFS-like illness. This trial is registered with Hong Kong Clinical
      Trial Register: HKCTR-1380. 

PMID- 25610474
TI  - Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral
      Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC
      ESI/MS Method.
AB  - Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and
      gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral
      administration of different prescriptions of Yizhi: Yizhi tablets or effective
      parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla
      alkaloids, EPG). At different predetermined time points after administration, the
      concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC
      ESI/MS method, and the main pharmacokinetic parameters were investigated. The
      results showed that the pharmacokinetic parameters C max and AUC0-infinity (P <
      0.05) were dramatically different after oral administration of different
      prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of
      GAS, HBA, and RIN in rats would interact with each other or be affected by other
      components in Yizhi. The rationality of the compatibility of Uncaria and
      Gastrodia elata as a classic "herb pair" has been verified from the
      pharmacokinetic viewpoint. 

PMID- 25610475
TI  - Immunostimulatory activity of protein hydrolysate from oviductus ranae on
      macrophage in vitro.
AB  - Oviductus Ranae is the dry oviduct of Rana chensinensis, which is also called R.
      chensinensis oil. Oviductus Ranae is a valuable Chinese crude drug and is
      recorded in the Pharmacopoeia of the People's Republic of China. The aim of this
      study was to investigate the immunostimulatory activity of protein hydrolysate of
      Oviductus Ranae (ORPH) and to assess its possible mechanism. Immunomodulatory
      activity of ORPH was examined in murine macrophage RAW 264.7 cells. The effect of
      ORPH on the phagocytic activity of macrophages was determined by the neutral red
      uptake assay. After treatment with ORPH, NO production levels in the culture
      supernatant were investigated by Griess assay. The mRNA and protein expressions
      of inducible nitric oxide synthase (iNOS) were detected by RT-PCR and Western
      blotting. The production of TNF-alpha, IL-1beta, and IL-6 after treatment with
      ORPH was measured using ELISA assay. In addition, NF-kappaB levels were also
      investigated by Western blot. The results showed that ORPH enhanced the
      phagocytosis of macrophage, increased productions of TNF-alpha, IL-1beta, IL-6,
      and NO in RAW 264.7 cells, and upregulated the mRNA and protein expression of
      iNOS. Besides, NF-kappaB, levels in RAW 264.7 cells were elevated after ORPH
      treatment. These findings suggested that ORPH might stimulate macrophage
      activities by activating the NF-kappaB pathway. 

PMID- 25610476
TI  - Anti-inflammatory and antiosteoclastogenic activities of parthenolide on human
      periodontal ligament cells in vitro.
AB  - Periodontitis is an inflammatory disease that causes osteolysis and tooth loss.
      It is known that the nuclear factor kappa B (NF-kappaB) signalling pathway plays
      a key role in the progression of inflammation and osteoclastogenesis in
      periodontitis. Parthenolide (PTL), a sesquiterpene lactone extracted from the
      shoots of Tanacetum parthenium, has been shown to possess anti-inflammatory
      properties in various diseases. In the study reported herein, we investigated the
      effects of PTL on the inflammatory and osteoclastogenic response of human
      periodontal ligament-derived cells (hPDLCs) and revealed the signalling pathways
      in this process. Our results showed that PTL decreased NF-kappaB activation, I
      kappaB degradation, and ERK activation in hPDLCs. PTL significantly reduced the
      expression of inflammatory (IL-1beta, IL-6, and TNF-alpha) and osteoclastogenic
      (RANKL, OPG, and M-CSF) genes in LPS-stimulated hPDLCs. In addition, PTL
      attenuated hPDLC-induced osteoclastogenic differentiation of macrophages
      (RAW264.7 cells), as well as reducing gene expression of osteoclast-related
      markers in RAW264.7 cells in an hPDLC-macrophage coculture model. Taken together,
      these results demonstrate the anti-inflammatory and antiosteoclastogenic
      activities of PTL in hPDLCs in vitro. These data offer fundamental evidence
      supporting the potential use of PTL in periodontitis treatment. 

PMID- 25610477
TI  - Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats:
      Mechanisms of Antioxidant and Anti-Inflammatory Action.
AB  - Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern
      traditional medicine to treat various inflammatory diseases. In the present
      study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae
      (GC-7101) on experimental gastric ulcer models and its mechanisms of action in
      gastric ulcer healing. The pharmacological activity of GC-7101 was investigated
      in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute
      gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its
      gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal
      NO content, nuclear translocation of NF-kappaB, mRNA expression of inflammatory
      cytokines, lipid peroxidation and glutathione content, and superoxide dismutase
      and catalase activities were measured. GC-7101 significantly attenuated
      development of acute gastric ulcer and accelerated the healing of acetic-acid
      induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101
      markedly enhanced gastric wall mucus content which was accompanied by increased
      mucosal PGE2 and NO production. Furthermore, treatment of GC-7101 exhibited anti
      inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase
      activity, NF-kappaB translocation, inflammatory cytokines mRNA expression, and
      lipid peroxidation and increased glutathione content and superoxide dismutase and
      catalase activities. These results demonstrated that GC-7101 possesses strong
      antiulcerogenic effect by modulating oxidative stress and proinflammatory
      mediators. 

PMID- 25610478
TI  - Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic
      Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine
      System.
AB  - Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis,
      hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal
      (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress,
      while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the
      mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported.
      Therefore, experiments were carried out to observe mechanism of LC-NE system in
      response to chronic immobilization stress (CIS) and explore the antidepressant
      effect of XYS. Rat model was established by CIS. LC morphology in rat was
      conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such
      as tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and corticotrophin
      releasing-factor (CRF) in LC were determined. Results showed that there were no
      discernible alterations in LC in rats. The serum NE concentrations, positive
      neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in
      model group were significantly increased compared to the control group. But XYS
      treated group displayed a significantly decreased in NE levels and expressions of
      TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC
      NE system to release NE and then result in a significant decrease in rats. XYS
      treatment can effectively improve depressive-like behaviors in rats through
      inhibition of LC-NE neurons activity. 

PMID- 25610479
TI  - Chemical basis of traditional medicines and new potential applications.

PMID- 25610480
TI  - Da-bu-yin-wan and qian-zheng-san to neuroprotect the mouse model of Parkinson's
      disease.
AB  - Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese
      medicinal formulas, were clinically employed to treat Parkinson's disease (PD).
      Our previous studies demonstrated neuroprotective effects of them on
      mitochondrial function in PD mice induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The purpose of this research was to investigate their
      possible mechanisms in the light of mitochondrial ATP-sensitive potassium
      (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA)
      neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by
      behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate
      (ATP) level in the midbrain tissue was detected by firefly luciferase method.
      MitoKATP channel subunits SUR1 and Kir6.2 mRNA and protein expressions were
      tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW
      and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent
      the loss of substantia nigra dopamine neurons, as well as increase ATP level in
      the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels
      with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit
      neuroprotective effects probably through the regulation of ATP level and mitoKATP
      channel subunit expressions. 

PMID- 25610481
TI  - Traditional medicines in the world: where to go next?

PMID- 25610482
TI  - Eastern medicine: from nutritional supplements to cancer research.

PMID- 25610483
TI  - New insights into the chemical and biochemical basis of the "yang-invigorating"
      action of chinese yang-tonic herbs.
AB  - In the practice of traditional Chinese medicine, many Yang-tonic herbs have been
      used for retarding the decline in bodily function and delaying the onset of age
      related diseases. Our earlier studies have demonstrated that Yang-invigorating
      herbs/formulations protect against oxidative injury in various organs and also
      extend the median lifespan in mice. This lifespan extension was associated with
      an upregulation of cellular antioxidant status including that of mitochondria
      whose functional capacity is also increased by "Yang-invigorating"
      herbs/formulations. In this paper, we propose that triterpenes and phytosterols,
      which are ubiquitously found in Yang-tonic herbs, may be the chemical entities
      responsible for enhancing mitochondrial functional and antioxidant capacity and
      thus the "Yang-invigorating" action. The biochemical mechanism underlying this
      "Yang-invigorating" action may involve a sustained production of low levels of
      mitochondrial reactive oxygen species (ROS) secondary to an increased activity of
      the electron transport chain, with the possible involvement of mitochondrial
      uncoupling. The increase in mitochondrial functional capacity can retard the
      decline in bodily function during aging, whereas the mitochondrial ROS production
      is instrumental in eliciting a glutathione antioxidant response via redox
      sensitive signaling pathways, which can delay the onset of age-related diseases. 

PMID- 25610484
TI  - Cognitive Enhancing and Neuroprotective Effect of the Embryo of the Nelumbo
      nucifera Seed.
AB  - The aim of the present study was to evaluate the effect of ENS on cognitive
      impairment induced by scopolamine and its potential neuroprotective effect
      against glutamate-induced cytotoxicity in HT22 cell and to investigate the
      underlying mechanisms. ENS (3, 10, 30, and 100 mg/kg), scopolamine (1 mg/kg), and
      donepezil (1 mg/kg) were administered to mice during a test period. Scopolamine
      impaired memory and learning in a water maze test and a passive avoidance test.
      The neuroprotective effect of ENS (10 and 100 MUg/mL) was investigated on
      glutamate-induced cell death in HT22 cells by MTT assay. We investigated
      acetylcholinesterase inhibition in hippocampus and antioxidant activity, ROS
      levels, and Ca(2+) influx in HT22 cells to elucidate the potential mechanisms of
      ENS. We found that ENS significantly ameliorated scopolamine-induced memory
      impairment and inhibited AChE activity in hippocampus. In vitro, ENS showed
      potent neuroprotective effects against glutamate-induced neurotoxicity in the
      HT22 cell. In addition, ENS induced a decrease in ROS production and
      intercellular Ca(2+) accumulation and showed DPPH radical and H2O2 scavenging
      activity. In conclusion, ENS showed both a memory improving effect and a
      neuroprotective effect. Our results indicate that ENS may be of use in the
      treatment and prevention of neurodegenerative disorders. 

PMID- 25610485
TI  - From prejudice to evidence: the case of rhizoma coptidis in singapore.
AB  - Rhizoma Coptidis (RC), commonly known as huanglian, is a herb frequently used in
      Traditional Chinese Medicine (TCM) prescriptions. Known to have "clearing damp
      heat, quenching fire and counteracting poison" properties, it was widely used in
      the Chinese community in Singapore. Berberine, an alkaloid isolated from RC, is
      known to have a wide array of therapeutic effects including antimicrobial,
      antineoplastic, and hepatoprotective effects. In 1978, RC was implicated in
      causing neonatal jaundice (NNJ) and kernicterus in neonates suffering from
      glucose-6-phosphate dehydrogenase (G6PD) deficiency, leading to the banning of RC
      and berberine in Singapore. More than three decades later, accumulating evidence
      based studies pointing to the safety of RC for general public and better
      understanding of G6PD deficiency, the Health Sciences Authority (HSA) in
      Singapore reviewed and lifted the prohibition on RC and berberine, turning a
      brand new chapter in the history of TCM in Singapore. This paper aims to review
      the safety of RC and berberine, using the prohibition of use and subsequent
      lifting of ban on RC and berberine in Singapore as an illustration to highlight
      the importance of evidence-based studies in Traditional Chinese Medicine (TCM). 

PMID- 25610486
TI  - Electroacupuncture for bladder function recovery in patients undergoing spinal
      anesthesia.
AB  - Purpose. To determine the efficacy of electroacupuncture on recovering
      postanesthetic bladder function. Materials and Methods. Sixty-one patients
      undergoing spinal anaesthesia were recruited and allocated into
      electroacupuncture or control group randomly. Patients in electroacupuncture
      group received electroacupuncture therapy whereas ones in control group were not
      given any intervention. Primary endpoint was incidence of bladder overdistension
      and postoperative urinary retention. Secondary endpoints included time to
      spontaneous micturition, voided volume, and adverse events. Results. All patients
      (31 in electroacupuncture group and 30 in control group) completed the
      evaluation. During postoperative follow-up, patients in electroacupuncture group
      presented a significant lower proportion of bladder overdistension than
      counterparts in control group (16.1% versus 53.3%, P < 0.01). However, no
      significant difference was found in incidence of postoperative urinary retention
      between the two groups (0% versus 6.7%, P > 0.05). Furthermore, a shorter time to
      spontaneous micturition was found in electroacupuncture group compared to control
      group (228 min versus 313 min, P < 0.001), whereas urine volume and adverse
      events had no significant difference between the two groups. Conclusions.
      Electroacupuncture reduced the proportion of bladder overdistension and shortened
      the time to spontaneous micturition in patients undergoing spinal anesthesia.
      Electroacupuncture may be a therapeutic strategy for postanesthetic bladder
      dysfunction. 

PMID- 25610487
TI  - Essential Oils from Fructus A. zerumbet Protect Human Aortic Endothelial Cells
      from Apoptosis Induced by Ox-LDL In Vitro.
AB  - Alpinia zerumbet is a miao folk medicinal plant widely used in the Guizhou
      Province of southwest China that contains several bioactive constituents and
      possesses protective effects against cardiovascular diseases. In the present
      study, we evaluated the protective effect of essential oils derived from Fructus
      Alpiniae zerumbet (EOFAZ) on oxidized lowdensity-lipoprotein- (ox-LDL-) induced
      apoptosis in human aortic endothelial cells (HAECs). Following exposure to ox
      LDL, HAECs presented with classical characteristics of apoptosis. However, EOFAZ
      ameliorated these morphological alterations and also inhibited the decrease in
      cell viability. In addition, EOFAZ abrogated the number of TUNEL or Hoechst 33258
      stained positive cells observed after ox-LDL challenge. Investigation into the
      mechanisms of this inhibition revealed that EOFAZ treatment resulted in a
      downregulation of Bax and Caspase-3 at both the protein and mRNA expression
      levels. Moreover, EOFAZ was found to upregulate Bcl-2 protein and mRNA levels and
      to attenuate ox-LDL-induced HAECs injury caused by apoptosis, revealing both its
      therapeutic potential for endothelial cell injury protection and its clinical
      application for atherosclerosis. 

PMID- 25610488
TI  - Evaluation of Antioxidant Activity and Acute Toxicity of Clausena excavata Leaves
      Extract.
AB  - Clausena excavata (Lour.), locally known as "Kemantu hitam," is a common plant in
      Malaysian folklore medicine. This study evaluated the antioxidant properties of
      the solvent extracts of C. excavata leaves and determined the acute toxicity of
      methanolic extract C. excavata (MECE) leaves in Sprague-Dawley rats. Harvested
      leaves were dried and subjected to solvent extraction using petroleum ether,
      chloroform, ethyl acetate and methanol in succession. The antioxidant activity of
      each extract was determined using the ferric-reducing antioxidant power (FRAP)
      and 2,2-diphenyl-1-picryl dihydrazyl (DPPH) radical scavenging activity. The
      total phenolic content (TPC) and total flavonoids content (TFC) were estimated by
      Folin-Ciocalteu and ethanolic aluminium chloride method, respectively. The
      chloroform extract was found to be highest in flavonoid content, while the
      methanolic extract showed the highest TPC and antioxidant activity. There was no
      mortality in rats treated with MECE leaves even at a high dose of 5000 mg/kg body
      weight. However, the MECE leaves produced mild to moderate pathological changes
      in the liver and kidneys, shown by mild degenerative changes and leucocyte
      infiltration. The extract did not affect the haematological parameters or
      relative weights of the liver or kidneys. Overall, the MECE leaves have potent
      antioxidant activity and are presumed safe to be used orally as health-promoting
      product at low to moderate doses. 

PMID- 25610489
TI  - Supplementation of Superfine Powder Prepared from Chaenomeles speciosa Fruit
      Increases Endurance Capacity in Rats via Antioxidant and Nrf2/ARE Signaling
      Pathway.
AB  - Chaenomeles speciosa fruit is a traditional herb medicine widely used in China.
      In this study, superfine powder of C. speciosa fruit (SCE), ground by supersonic
      nitrogen airflow at -140 degrees C, was investigated to assess its in vitro
      antioxidant activity and in vivo antiphysical fatigue activity. SCE was
      homogenous (d < 10 MUm) and rich in antioxidants like polyphenols, saponins,
      oleanolic acid, ursolic acid, ascorbic acid, and SOD. According to the in vitro
      experiments, SCE displayed promising antioxidant activity with powerful FARP, SC
      DPPH, and SC-SAR activities. According to the in vivo experiments, rats
      supplemented with SCE had prolonged exhaustive swimming time (57%) compared to
      the nonsupplemented rats. Meanwhile, compared to the nonsupplemented rats, the
      SCE-supplemented rats had higher levels of blood glucose and liver and muscular
      glycogen and lower levels of LA and BUN. Lower MDA, higher antioxidant enzymes
      (SOD, CAT, and GSH-Px) activities, and upregulated Nrf2/ARE mediated antioxidant
      enzymes (HO-1, Trx, GCLM, and GCLC) expression were also detected in the
      supplemented group. This study indicates that SCE is a potent antioxidant and
      antifatigue agent, and SCE could be a promising raw material for the food and
      pharmaceutical industries. 

PMID- 25610490
TI  - Antiatherosclerotic effect of korean red ginseng extract involves regulator of g
      protein signaling 5.
AB  - Regulator of G-protein signaling 5 (RGS5), an inhibitor of Galpha(q) and
      Galpha(i) activation, has been reported to have antiatherosclerosis. Previous
      studies showed antiatherosclerotic effect of Korean red ginseng water extract
      (KRGE) via multiple signaling pathways. However, potential protective effect of
      KRGE through RGS5 expression has not been elucidated. Here, we investigated the
      antiatherosclerotic effect of KRGE in vivo and in vitro and its role on RGS5 mRNA
      expression. Elevated levels of total cholesterol, lactate dehydrogenase (LDH),
      and triglyceride (TG) in western diet groups of low-density lipoprotein receptor
      deficient LDLr(-/-) mice were reversed by oral administration of KRGE. KRGE
      suppressed transcriptional activity of tumor necrotic factor alpha (TNF-alpha),
      interleukin-6 (IL-6), and leptin in adipose tissue. It also potently repressed
      western diet-induced atheroma formation in aortic sinus. While KRGE showed
      reduced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase
      2 (COX-2), IL-1beta, IL-6, and TNF-alpha in LPS-stimulated RAW264.7 cells, it
      enhanced mRNA expression of RGS5. Moreover, RGS5 siRNA transfection of microglia
      cells pretreated with KRGE reversed its inhibitory effect on the expression of
      iNOS, COX-2, and IL-1beta mRNA. In conclusion, KRGE showed antiatherosclerotic
      and anti-inflammatory effects in western diet fed LDLr(-/-) mice and this effect
      could partly be mediated by RGS5 expression. 

PMID- 25610491
TI  - The power of oral and nasal calls to discriminate individual mothers and
      offspring in red deer, Cervus elaphus.
AB  - BACKGROUND: In most species, acoustical cues are crucial for mother-offspring
      recognition. Studies of a few species of ungulates showed that potential for
      individual recognition may differ between nasal and oral contact calls. RESULTS:
      Vocalizations of 28 hinds and 31 calves of farmed Iberian red deer (Cervus
      elaphus hispanicus) were examined with discriminant function analyses (DFA) to
      determine whether acoustic structure of their oral and nasal contact calls
      encodes information about the caller's identity. Contact calls were elicited by
      brief separation of individually identified animals by a distance over 10 m or by
      a bar fence. Both oral and nasal calls of both hinds and calves showed high
      potential to discriminate individuals. In hinds, individuality was significantly
      higher in the oral than in the nasal calls, whereas in calves, individuality was
      equally well expressed in both oral and nasal calls. For calves, the maximum
      fundamental frequency was higher and the duration was longer in oral calls than
      in nasal calls. For hinds, the maximum fundamental frequency and the duration
      were indistinguishable between oral and nasal calls. Compared to the pooled
      sample of oral and nasal calls, separate oral or nasal call samples provided
      better classifying accuracy to individual in either hinds or calves.
      Nevertheless, in both hinds and calves, even in the pooled sample of oral and
      nasal calls, the degree of individual identity was 2-3 times greater than
      expected by chance. For hinds that provided calls in both years, cross-validation
      of calls collected in 2012 with discriminant functions created with calls from
      2011 showed a strong decrease of classifying accuracy to individual. CONCLUSIONS:
      These results suggest different potentials of nasal and oral calls to allow the
      discrimination of individuals among hinds, but not among red deer calves. The
      high potential of individual recognition even with the pooled sample of oral and
      nasal calls allows mother and young to remember only one set of acoustic
      variables for mutual vocal recognition. Poor between-year stability of individual
      characteristics of hind oral and nasal calls would require updating keys to
      individual recognition each calving season.

PMID- 25610492
TI  - Mapping mutations in plant genomes with the user-friendly web application
      CandiSNP.
AB  - BACKGROUND: Analysis of mutants isolated from forward-genetic screens has
      revealed key components of several plant signalling pathways. Mapping mutations
      by position, either using classical methods or whole genome high-throughput
      sequencing (HTS), largely relies on the analysis of genome-wide polymorphisms in
      F2 recombinant populations. Combining bulk segregant analysis with HTS has
      accelerated the identification of causative mutations and has been widely adopted
      in many research programmes. A major advantage of HTS is the ability to perform
      bulk segregant analysis after back-crossing to the parental line rather than out
      crossing to a polymorphic ecotype, which reduces genetic complexity and avoids
      issues with phenotype penetrance in different ecotypes. Plotting the positions of
      homozygous polymorphisms in a mutant genome identifies areas of low recombination
      and is an effective way to detect molecular linkage to a phenotype of interest.
      RESULTS: We describe the use of single nucleotide polymorphism (SNP) density
      plots as a mapping strategy to identify and refine chromosomal positions of
      causative mutations from screened plant populations. We developed a web
      application called CandiSNP that generates density plots from user-provided SNP
      data obtained from HTS. Candidate causative mutations, defined as SNPs causing
      non-synonymous changes in annotated coding regions are highlighted on the plots
      and listed in a table. We use data generated from a recent mutant screen in the
      model plant Arabidopsis thaliana as proof-of-concept for the validity of our
      tool. CONCLUSIONS: CandiSNP is a user-friendly application that will aid in novel
      discoveries from forward-genetic mutant screens. It is particularly useful for
      analysing HTS data from bulked back-crossed mutants, which contain fewer
      polymorphisms than data generated from out-crosses. The web-application is freely
      available online at http://candisnp.tsl.ac.uk.

PMID- 25610493
TI  - Mathematical methods in biomedical imaging 2014.

PMID- 25610494
TI  - Prolonged duration of surgery is not a risk factor for postoperative
      complications in patients undergoing total thyroidectomy: a single center
      experience in 305 patients.
AB  - BACKGROUND: Hypocalcemia and nerve injury are the most severe complications after
      thyroid surgery. The duration of surgery has not been previously considered as a
      risk factor for postoperative complications in patients undergoing total
      thyroidectomy. We sort to investigate the influence of prolonged surgery on
      postoperative complications in patients undergoing total thyroidectomy. METHODS:
      We hypothesized that a threshold of > 120 minutes of surgical time could
      represent a surrogate marker for postoperative complications in patients
      undergoing total thyroidectomy for benign thyroid disorders. The study population
      was divided into two groups based on the median duration of surgery (120 min):
      group I <= 120 minutes (control group), group II > 120 minutes (study group). The
      charts of eligible patients undergoing total thyroidectomy within a six-year
      period from January 1(st) 2006 to December 31(st) 2012 were reviewed. The primary
      outcomes included the rates postoperative hypocalcemia and recurrent laryngeal
      nerve palsy. The secondary outcomes included the rates of postoperative
      hemorrhage, wound dehiscence and length of hospital stay. RESULTS: 305 cases of
      thyroidectomy were included for analysis; 130 (42.6%) control group and 175
      (57.4%) study group. Transient (15.4% vs 19.4%) and permanent (3.8% vs. 2.9%)
      hypocalcemia were recorded in control and study group respectively. The incidence
      of nerve palsy was 1.5% in the control group and 1.4% in the study group. The
      mean length of postoperative hospital stay was 3d in both groups. There was no
      significant difference amongst both groups with regard to postoperative bleeding
      (p = 0.57) and wound dehiscence (p = 0.31). Prolonged surgery (> 120 min) was not
      identified as a risk factor for increased postoperative complication. CONCLUSION:
      Prolonged duration of surgery > 120 minutes is not a surrogate marker for
      postoperative complications in patients undergoing total thyroidectomy.

PMID- 25610496
TI  - Open versus endoscopic bone resection of the dorsolateral calcaneal edge: a
      cadaveric analysis comparing three dimensional CT scans.
AB  - BACKGROUND: It has been claimed that endoscopic calcaneoplasty offers some
      advantages over open techniques in the surgical treatment of Haglund's deformity
      due to reduced postoperative complications like stiffness and pain. Bony over
      resection places patients at risk of these complications. The resulting question
      with regard to the quantitative differences of the extent of the bone removed
      using these two techniques has not yet been answered. The purpose of the study
      was to determine the resection volume of calcaneal bone for open and endoscopic
      surgical techniques. METHODS: 16 feet obtained from body donors were operated on
      in equal parts using either open surgical or endoscopic techniques, with the
      technique selected on a random basis. High-resolution CT scans were obtained
      before and after the interventional procedure and analysed to obtain 3-D polygon
      models. Post-operative models were subtracted from pre-operative models to
      provide the volume change resulting from the intervention. This was then
      correlated with the bone mineral density (BMD) of the preparation. RESULTS: The
      extent of bony resection was greater in open surgical techniques than in
      endoscopic approaches. The average volume of bone resection was 0.80 (+/-0.34)
      cm(3) in the endoscopic group and 3.04 (+/-2.91) cm(3) in the group that
      underwent open surgery. After adjustment for bone mineral density the extent of
      the resection was significantly larger (p = 0.018) in the group undergoing open
      surgery. The two groups did not differ significantly with regard to BMD (p >
      0.1). The extent of the resection fell by 0.011 cm(3) per 1 mg/cm(3) areal bone
      mineral density, i.e., a slightly lower degree of bone resection was associated
      with a higher bone mineral density. CONCLUSIONS: Assuming that the resection
      volume was adequate to treat the patient's complaints a smaller resection volume
      seen in our study using an endoscopic technique might lead to fewer postoperative
      complaints and faster recovery.

PMID- 25610495
TI  - Non-coding RNA derived from a conservative subtelomeric tandem repeat in chicken
      and Japanese quail somatic cells.
AB  - BACKGROUND: Subtelomeres are located close to the ends of chromosomes and
      organized by tandemly repetitive sequences, duplicated copies of genes,
      pseudogenes and retrotransposons. Transcriptional activity of tandemly organized
      DNA at terminal chromosomal regions and the distribution of subtelomere-derived
      non-coding RNAs are poorly investigated. Here we aimed to analyze transcriptional
      activity of subtelomeric tandem repeat in somatic tissues and cultured cells of
      birds. We focused on tissue-specific differences of subtelomeric repeats
      transcription, structure of the resulting transcripts and the behavior of
      subtelomere-derived RNA during mitosis. RESULTS: Transcriptional activity of
      short subtelomeric PO41 ("pattern of 41 bp") tandem repeat in the somatic and
      cultured cells of chicken (Gallus gallus domesticus) and Japanese quail (Coturnix
      coturnix japonica) was examined using RNA fluorescence in situ hybridization
      approach. We discovered transcripts from both strands of the PO41 repeat in
      chicken MDCC-MSB1 cells as well as in chicken and Japanese quail somatic tissues,
      such as tissues of cerebellum, telencephalon, muscles, oviduct, small and large
      intestine. Normal somatic and transformed cells demonstrate similar distribution
      of PO41 repeat transcripts in interphase nuclei. We revealed one or two major
      foci of PO41 repeat transcripts associated with RNA polymerase II, representing
      nascent RNA, and dispersed PO41 repeat transcripts localized in euchromatin or
      interchromatin space, representing released RNA. During mitosis PO41 non-coding
      RNA distribute between condensed chromosomes till anaphase, when they concentrate
      at the cleavage plane. At telophase, clusters of PO41 RNA surround terminal
      regions of chromosomes. Treatments with RNases of different substrate specificity
      indicate that PO41 repeat transcripts are single-stranded RNAs with short double
      stranded regions due to appearance of inverted repeats. CONCLUSION: Transcription
      of a subtelomeric tandem repeat in avian somatic cells is reported here for the
      first time. PO41 repeat transcription is conserved among Galliformes and has
      similar pattern in somatic tissues. We demonstrated redistribution of non-coding
      PO41 RNA occurring during the cell cycle. Potential regulatory role of the PO41
      repeat transcripts in RNA-dependent process of subtelomere heterochromatin
      maintenance is discussed.

PMID- 25610497
TI  - Biomechanical aspects of segmented arch mechanics combined with power arm for
      controlled anterior tooth movement: A three-dimensional finite element study.
AB  - The porpose of this study was to determine the optimal length of power arms for
      achieving controlled anterior tooth movement in segmented arch mechanics combined
      with power arm. A three-dimensional finite element method was applied for the
      simulation of en masse anterior tooth retraction in segmented power arm
      mechanics. The type of tooth movement, namely, the location of center of rotation
      of the maxillary central incisor in association with power arm length, was
      calculated after the retraction force was applied. When a 0.017 * 0.022-in
      archwire was inserted into the 0.018-in slot bracket, bodily movement was
      obtained at 9.1 mm length of power arm, namely, at the level of 1.8 mm above the
      center of resistance. In case a 0.018 * 0.025-in full-size archwire was used,
      bodily movement of the tooth was produced at the power arm length of 7.0 mm,
      namely, at the level of 0.3 mm below the center of resistance. Segmented arch
      mechanics required shorter length of power arms for achieving any type of
      controlled anterior tooth movement as compared to sliding mechanics. Therefore,
      this space closing mechanics could be widely applied even for the patients whose
      gingivobuccal fold is shallow. The segmented arch mechanics combined with power
      arm could provide higher amount of moment-to-force ratio sufficient for
      controlled anterior tooth movement without generating friction, and vertical
      forces when applying retraction force parallel to the occlusal plane. It is,
      therefore, considered that the segmented power arm mechanics has a simple
      appliance design and allows more efficient and controllable tooth movement. 

PMID- 25610498
TI  - Portuguese Journal of Pulmonology and Brazilian Journal of Pulmonology--"aquele
      abraco" ("a great big hug").

PMID- 25610499
TI  - Gender differences in the perception of asthma and respiratory symptoms in a
      population sample of asthma patients in four Brazilian cities.
AB  - OBJECTIVE: To evaluate the impact of asthma, by gender, in a population sample of
      asthma patients in Brazil. METHODS: We conducted face-to-face interviews with 400
      subjects (> 12 years of age) included in a national probability telephone sample
      of asthma patients in the Brazilian state capitals of Sao Paulo, Rio de Janeiro,
      Curitiba, and Salvador. Each of those 400 subjects completed a 53-item
      questionnaire that addressed five asthma domains: symptoms; impact of asthma on
      quality of life; perception of asthma control; exacerbations; and
      treatment/medication. RESULTS: Of the 400 patients interviewed, 272 (68%) were
      female. In relation to respiratory symptoms, the proportion of women reporting
      extremely bothersome symptoms (cough with sputum, tightness in the chest,
      cough/shortness of breath/tightness in the chest during exercise, nocturnal
      shortness of breath, and nocturnal cough) was greater than was that of men.
      Daytime symptoms, such as cough, shortness of breath, wheezing, and tightness in
      the chest, were more common among women than among men. Women also more often
      reported that their asthma interfered with normal physical exertion, social
      activities, sleep, and life in general. Regarding the impact of asthma on quality
      of life, the proportion of subjects who reported that asthma caused them to feel
      that they had no control over their lives and affected the way that they felt
      about themselves was also greater among women than among men. CONCLUSIONS: Among
      women, asthma tends to be more symptomatic, as well as having a more pronounced
      effect on activities of daily living and on quality of life.

PMID- 25610500
TI  - Efficacy and safety of the single-capsule combination of fluticasone/formoterol
      in patients with persistent asthma: a non-inferiority trial.
AB  - OBJECTIVE: Fluticasone and formoterol are effective in the treatment of asthma.
      When a corticosteroid alone fails to control asthma, combination therapy is the
      treatment of choice. The objective of this study was to compare the efficacy and
      safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone
      alone (FLU), and the single-capsule combination of fluticasone/formoterol
      (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma.
      METHODS: This was a randomized, multicenter, open phase III trial conducted in
      Brazil. The primary efficacy analysis was the assessment of non-inferiority
      between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L) at the final
      visit. The secondary analyses were PEF, level of asthma control, serum cortisol
      levels, frequency of adverse events, adherence to treatment, and appropriate
      inhaler use. RESULTS: We randomized 243 patients to three groups: FLU/FOR (n =
      79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV1 after 12 weeks
      of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L
      (95% CI: -0.06 to 0.49), whereas the difference between the FLU/FOR and FLU
      groups was 0.26 L (95% CI: -0.002 to 0.52). Non-inferiority was demonstrated by
      the difference between the lower limits of the two 95% CIs (-0.06 vs. -0.002).
      The level of asthma control and PEF were significantly greater in the FLU/FOR and
      BUD/FOR groups than in the FLU group. There were no significant differences among
      the groups regarding patient adherence, patient inhaler use, or safety profile of
      the formulations. CONCLUSIONS: The single-capsule combination of FLU/FOR showed
      non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and
      safety, making it a new treatment option for persistent asthma.

PMID- 25610501
TI  - Left ventricular dysfunction in patients with suspected pulmonary arterial
      hypertension.
AB  - OBJECTIVE: To evaluate the role of right heart catheterization in the diagnosis
      of pulmonary arterial hypertension (PAH). METHODS: We evaluated clinical,
      functional, and hemodynamic data from all patients who underwent right heart
      catheterization because of diagnostic suspicion of PAH--in the absence of severe
      left ventricular dysfunction (LVD), significant changes in pulmonary function
      tests, and ventilation/perfusion lung scintigraphy findings consistent with
      chronic pulmonary thromboembolism--between 2008 and 2013 at our facility.
      RESULTS: During the study period, 384 patients underwent diagnostic cardiac
      catheterization at our facility. Pulmonary hypertension (PH) was confirmed in 302
      patients (78.6%). The mean age of those patients was 48.7 years. The patients
      without PH showed better hemodynamic profiles and lower levels of B-type
      natriuretic peptide. Nevertheless, 13.8% of the patients without PH were
      categorized as New York Heart Association functional class III or IV. Of the 218
      patients who met the inclusion criteria, 40 (18.3%) and 178 (81.7%) were
      diagnosed with PH associated with LVD (PH-LVD) and with PAH, respectively. The
      patients in the HP-LVD group were significantly older than were those in the PAH
      group (p < 0.0001). CONCLUSIONS: The proportional difference between the PAH and
      PH-LVD groups was quite significant, considering the absence of echocardiographic
      signs suggestive of severe LVD during the pre-catheterization investigation. Our
      results highlight the fundamental role of cardiac catheterization in the
      diagnosis of PAH, especially in older patients, in whom the prevalence of LVD
      that has gone undiagnosed by non-invasive tests is particularly relevant.

PMID- 25610502
TI  - Epidemiological aspects of and risk factors for wheezing in the first year of
      life.
AB  - OBJECTIVE: To determine, in a sample of infants, the prevalence of and risk
      factors for occasional wheezing (OW) and recurrent wheezing-wheezy baby syndrome
      (WBS). METHODS: Parents of infants (12-15 months of age) completed the
      International Study of Wheezing in Infants questionnaire. RESULTS: We included
      1,269 infants residing in the city of Blumenau, Brazil. Of those, 715 (56.34%)
      had a history of wheezing, which was more common among boys. The prevalences of
      OW and WBS were 27.03% (n = 343) and 29.31% (n = 372), respectively. On average,
      the first wheezing episode occurred at 5.55 +/- 2.87 months of age. Among the 715
      infants with a history of wheezing, the first episode occurred within the first
      six months of life in 479 (66.99%), and 372 (52.03%) had had three or more
      episodes. Factors associated with wheezing in general were pneumonia; oral
      corticosteroid use; a cold; attending daycare; having a parent with asthma or
      allergies; mother working outside the home; male gender; no breastfeeding; and
      mold. Factors associated with WBS were a cold; physician-diagnosed asthma; ER
      visits; corticosteroid use; pneumonia; bronchitis; dyspnea; attending daycare;
      bronchodilator use; having a parent with asthma; no breastfeeding; mother working
      outside the home; and a dog in the household. CONCLUSIONS: The prevalence of
      wheezing in the studied population was high (56.34%). The etiology was
      multifactorial, and the risk factors were intrinsic and extrinsic (respiratory
      tract infections, allergies, attending daycare, and early wheezing). The high
      prevalence and the intrinsic risk factors indicate the need and the opportunity
      for epidemiological and genetic studies in this population. In addition, mothers
      should be encouraged to prolong breastfeeding and to keep infants under six
      months of age out of daycare.

PMID- 25610503
TI  - Effects of home-based respiratory muscle training in children and adolescents
      with chronic lung disease.
AB  - OBJECTIVE: Respiratory muscle weakness is a functional repercussion of chronic
      lung disease (CLD). The objective of this study was to assess the effects of home
      based respiratory muscle training (RMT) in children and adolescents with CLD or
      neuromuscular disease (NMD). METHODS: This was a quasi-experimental study
      involving children and adolescents with CLD or NMD. Before and after 6 months of
      home-based RMT, we measured respiratory muscle strength (MIP and MEP), PEF, and
      peak cough flow (PCF). We made statistical comparisons between the pre-RMT and
      post-RMT values, as well as evaluating the correlation between the duration and
      effect of RMT. RESULTS: The study included 29 patients, with a mean age of 12
      years (range, 5-17 years), of whom 18 (62.1%) were male. The CLD group comprised
      11 patients (37.9%), and the NMD group comprised 18 (62.1%). The mean duration of
      the RMT was 60 weeks (range, 46-90 weeks) in the CLD group and 39 weeks (range,
      24-89 weeks) in the NMD group. In comparison with the pre-RMT values, the post
      RMT values for MIP and MEP were significantly higher in both groups, whereas
      those for PEF and PCF were significantly higher only in the NMD group. We found
      no correlation between the duration and the effect of RMT. CONCLUSIONS: Home
      based RMT appears to be an effective strategy for increasing respiratory muscle
      strength in children and adolescents with CLD or NMD, although it increased the
      ability to cough effectively only in those with NMD.

PMID- 25610504
TI  - Correlates of experimentation with smoking and current cigarette consumption
      among adolescents.
AB  - OBJECTIVE: The aim of this study was to analyze social characteristics and stress
      as correlates of cigarette smoking in adolescence. The main intent was to
      identify elements that distinguish adolescents who had experimented with smoking
      and did not progress to regular smoking from those who became current smokers.
      METHODS: Students at 10 high schools in the city of Ribeirao Preto, Brazil,
      completed a questionnaire based on an instrument employed in a similar large
      scale study. The students were classified as never-smokers or experimenters. The
      experimenters were subcategorized as having become current smokers or
      nonprogressors. Analyses were performed using adjusted logistic models. RESULTS:
      A total of 2,014 students (mean age, 16.2 +/- 1.1 years; females, 53%) completed
      the questionnaire. We categorized 1,283 students (63.7%) as never-smokers, 244
      (12.1%) as current smokers, and 487 (24.2%) as nonprogressors. We found that
      experimentation with smoking was associated with being held back a grade in
      school (OR = 1.80), alcohol intake (low/occasional, OR = 8.92; high/regular, OR =
      2.64), illicit drug use (OR = 9.32), having a sibling or cousin who smokes (OR =
      1.39), having a friend who smokes (OR = 2.08), and high levels of stress (in
      females only, OR = 1.32). Factors associated with an increased risk of
      transitioning from experimenter to current smoker were alcohol intake
      (low/occasional, OR = 3.28; high/regular, OR = 2.16), illicit drug use (OR =
      3.61), and having a friend who smokes (OR = 7.20). CONCLUSIONS: Current smoking
      was associated with a profile of socioeconomic correlates different from that
      associated with experimentation only. Our data (showing that current smoking was
      associated with having a friend who smokes, alcohol intake, and illicit drug use)
      suggest the need for comprehensive approaches to discourage substance use during
      adolescence.

PMID- 25610505
TI  - Quantitative culture of endotracheal aspirate and BAL fluid samples in the
      management of patients with ventilator-associated pneumonia: a randomized
      clinical trial.
AB  - OBJECTIVE: To compare 28-day mortality rates and clinical outcomes in ICU
      patients with ventilator-associated pneumonia according to the diagnostic
      strategy used. METHODS: This was a prospective randomized clinical trial. Of the
      73 patients included in the study, 36 and 37 were randomized to undergo BAL or
      endotracheal aspiration (EA), respectively. Antibiotic therapy was based on
      guidelines and was adjusted according to the results of quantitative cultures.
      RESULTS: The 28-day mortality rate was similar in the BAL and EA groups (25.0%
      and 37.8%, respectively; p = 0.353). There were no differences between the groups
      regarding the duration of mechanical ventilation, antibiotic therapy, secondary
      complications, VAP recurrence, or length of ICU and hospital stay. Initial
      antibiotic therapy was deemed appropriate in 28 (77.8%) and 30 (83.3%) of the
      patients in the BAL and EA groups, respectively (p = 0.551). The 28-day mortality
      rate was not associated with the appropriateness of initial therapy in the BAL
      and EA groups (appropriate therapy: 35.7% vs. 43.3%; p = 0.553; and inappropriate
      therapy: 62.5% vs. 50.0%; p = 1.000). Previous use of antibiotics did not affect
      the culture yield in the EA or BAL group (p = 0.130 and p = 0.484, respectively).
      CONCLUSIONS: In the context of this study, the management of VAP patients, based
      on the results of quantitative endotracheal aspirate cultures, led to similar
      clinical outcomes to those obtained with the results of quantitative BAL fluid
      cultures. (Brazilian Registry of Clinical Trials--ReBEC; identification number
      RBR-86DCDX [http://www.ensaiosclinicos.gov.br]).

PMID- 25610506
TI  - Facial pressure zones of an oronasal interface for noninvasive ventilation: a
      computer model analysis.
AB  - OBJECTIVE: To study the effects of an oronasal interface (OI) for noninvasive
      ventilation, using a three-dimensional (3D) computational model with the ability
      to simulate and evaluate the main pressure zones (PZs) of the OI on the human
      face. METHODS: We used a 3D digital model of the human face, based on a pre
      established geometric model. The model simulated soft tissues, skull, and nasal
      cartilage. The geometric model was obtained by 3D laser scanning and post
      processed for use in the model created, with the objective of separating the
      cushion from the frame. A computer simulation was performed to determine the
      pressure required in order to create the facial PZs. We obtained descriptive
      graphical images of the PZs and their intensity. RESULTS: For the graphical
      analyses of each face-OI model pair and their respective evaluations, we ran 21
      simulations. The computer model identified several high-impact PZs in the nasal
      bridge and paranasal regions. The variation in soft tissue depth had a direct
      impact on the amount of pressure applied (438-724 cmH2O). CONCLUSIONS: The
      computer simulation results indicate that, in patients submitted to noninvasive
      ventilation with an OI, the probability of skin lesion is higher in the nasal
      bridge and paranasal regions. This methodology could increase the applicability
      of biomechanical research on noninvasive ventilation interfaces, providing the
      information needed in order to choose the interface that best minimizes the risk
      of skin lesion.

PMID- 25610507
TI  - Impact of the type of mask on the effectiveness of and adherence to continuous
      positive airway pressure treatment for obstructive sleep apnea.
AB  - Continuous positive airway pressure (CPAP) is the gold standard for the treatment
      of obstructive sleep apnea (OSA). Although CPAP was originally applied with a
      nasal mask, various interfaces are currently available. This study reviews
      theoretical concepts and questions the premise that all types of interfaces
      produce similar results. We revised the evidence in the literature about the
      impact that the type of CPAP interface has on the effectiveness of and adherence
      to OSA treatment. We searched the PubMed database using the search terms "CPAP",
      "mask", and "obstructive sleep apnea". Although we identified 91 studies, only 12
      described the impact of the type of CPAP interface on treatment effectiveness (n
      = 6) or adherence (n = 6). Despite conflicting results, we found no consistent
      evidence that nasal pillows and oral masks alter OSA treatment effectiveness or
      adherence. In contrast, most studies showed that oronasal masks are less
      effective and are more often associated with lower adherence and higher CPAP
      abandonment than are nasal masks. We concluded that oronasal masks can compromise
      CPAP OSA treatment adherence and effectiveness. Further studies are needed in
      order to understand the exact mechanisms involved in this effect. 

PMID- 25610508
TI  - Infected tracheal diverticulum: a rare association with alpha-1 antitrypsin
      deficiency.
AB  - Tracheal diverticulum, defined as a benign outpouching of the tracheal wall, is
      rarely diagnosed in clinical practice. It can be congenital or acquired in
      origin, and most cases are asymptomatic, typically being diagnosed postmortem. We
      report a case of a 69-year-old woman who was hospitalized after presenting with
      fever, fatigue, pleuritic chest pain, and a right neck mass complicated by
      dysphagia. Her medical history was significant: pulmonary emphysema (alpha-1
      antitrypsin deficiency); bronchiectasis; and thyroidectomy. On physical
      examination, she presented diminished breath sounds and muffled heart sounds,
      with a systolic murmur. Laboratory tests revealed elevated inflammatory markers,
      a CT scan showed an air-filled, multilocular mass in the right tracheal wall, and
      magnetic resonance imaging confirmed the CT findings. Fiberoptic bronchoscopy
      failed to reveal any abnormalities. Nevertheless, the patient was diagnosed with
      tracheal diverticulum. The treatment approach was conservative, consisting mainly
      of antibiotics. After showing clinical improvement, the patient was discharged. 

PMID- 25610509
TI  - A six-minute step test protocol for the investigation of dyspnea.

PMID- 25610510
TI  - Preserving the intercostal nerves as a goal in thoracotomy.

PMID- 25610511
TI  - Calyceal diverticulum of the kidney - diagnostic imaging dilemma in pediatric
      patients - case report.
AB  - BACKGROUND: Calyceal diverticula are rarely diagnosed in children. They can mimic
      other renal cystic lesions and correct diagnosis can be difficult to establish.
      Connection between fluid collection and collecting system confirmed by imaging
      studies is the key diagnostic finding. CASE REPORT: In this report we present a
      case of pediatric patient with calyceal diverticulum, with initial
      ultrasonographic diagnosis of simple renal cyst. Final diagnosis was established
      after extended diagnostics following infection of a fluid collection.
      CONCLUSIONS: 1. Differential diagnosis of well-circumscribed solitary renal fluid
      collections in children should include particularly: simple cyst, calyceal
      diverticulum and the first demonstration of ADPKD. 2. Diagnosis of calyceal
      diverticulum should be confirmed by contrast studies. 3. Standard management of
      calyceal diverticula in children includes ultrasonographic follow-up and
      conservative treatment and rarely requires surgical intervention.

PMID- 25610512
TI  - Ripple structure-generated hybrid electrokinetics for on-chip mixing and
      separating of functionalized beads.
AB  - We present an electrokinetics-based microfluidic platform that is capable of on
      chip manipulating, mixing, and separating microparticles through adjusting the
      interrelated magnitudes of dielectrophoresis and AC electroosmosis. Hybrid
      electrokinetic phenomenon is generated from an electric field-induced micro
      ripple structure made of ultraviolet-curable glue. Size-dependent particle
      separation and selective removal over the ripple structure is demonstrated
      successfully. Varying the waveform from sine-wave to square-wave allows
      generating a fluid convection at specific positions to mix the antibody
      functionalized beads and antigen. Potential application in the bead-based
      immunoassay was also demonstrated for immuno-reaction and subsequently separating
      the bead-bead aggregate and non-binding beads on-chip. 

PMID- 25610513
TI  - A microfluidic device enabling high-efficiency single cell trapping.
AB  - Single cell trapping increasingly serves as a key manipulation technique in
      single cell analysis for many cutting-edge cell studies. Due to their inherent
      advantages, microfluidic devices have been widely used to enable single cell
      immobilization. To further improve the single cell trapping efficiency, this
      paper reports on a passive hydrodynamic microfluidic device based on the "least
      flow resistance path" principle with geometry optimized in line with
      corresponding cell types. Different from serpentine structure, the core trapping
      structure of the micro-device consists of a series of concatenated T and inverse
      T junction pairs which function as bypassing channels and trapping constrictions.
      This new device enhances the single cell trapping efficiency from three aspects:
      (1) there is no need to deploy very long or complicated channels to adjust flow
      resistance, thus saving space for each trapping unit; (2) the trapping works in a
      "deterministic" manner, thus saving a great deal of cell samples; and (3) the
      compact configuration allows shorter flowing path of cells in multiple channels,
      thus increasing the speed and throughput of cell trapping. The mathematical model
      of the design was proposed and optimization of associated key geometric
      parameters was conducted based on computational fluid dynamics (CFD) simulation.
      As a proof demonstration, two types of PDMS microfluidic devices were fabricated
      to trap HeLa and HEK-293T cells with relatively significant differences in cell
      sizes. Experimental results showed 100% cell trapping and 90% single cell
      trapping over 4 * 100 trap sites for these two cell types, respectively. The
      space saving is estimated to be 2-fold and the cell trapping speed enhancement to
      be 3-fold compared to previously reported devices. This device can be used for
      trapping various types of cells and expanded to trap cells in the order of tens
      of thousands on 1-cm(2) scale area, as a promising tool to pattern large-scale
      single cells on specific substrates and facilitate on-chip cellular assay at the
      single cell level. 

PMID- 25610514
TI  - Characterization of anomalous movements of spherical living cells on a silicon
      dioxide glassy substrate.
AB  - The random walk of spherical living cells on a silicon dioxide glassy substrate
      was studied experimentally and numerically. This random walk trajectory exhibited
      erratic dancing, which seemingly obeyed anomalous diffusion (i.e., Levy-like
      walk) rather than normal diffusion. Moreover, the angular distribution (-pi to
      pi) of the cells' trajectory followed a "U-shaped pattern" in comparison to the
      uniform distribution seen in the movements of negatively charged polystyrene
      microspheres. These effects could be attributable to the homeostasis-driven
      structural resilient character of cells and physical interactions derived from
      temporarily retained nonspecific binding due to weak forces between the cells and
      substrates. Our results provide new insights into the stochastic behavior of
      mesoscopic biological particles with respect to structural properties and
      physical interactions. 

PMID- 25610515
TI  - Screening ion-channel ligand interactions with passive pumping in a microfluidic
      bilayer lipid membrane chip.
AB  - We describe a scalable artificial bilayer lipid membrane platform for rapid
      electrophysiological screening of ion channels and transporters. A passive
      pumping method is used to flow microliter volumes of ligand solution across a
      suspended bilayer within a microfluidic chip. Bilayers are stable at flow rates
      up to ~0.5 MUl/min. Phospholipid bilayers are formed across a
      photolithographically defined aperture made in a dry film resist within the
      microfluidic chip. Bilayers are stable for many days and the low shunt
      capacitance of the thin film support gives low-noise high-quality single ion
      channel recording. Dose-dependent transient blocking of alpha-hemolysin with beta
      cyclodextrin (beta-CD) and polyethylene glycol is demonstrated and dose-dependent
      blocking studies of the KcsA potassium channel with tetraethylammonium show the
      potential for determining IC50 values. The assays are fast (30 min for a complete
      IC50 curve) and simple and require very small amounts of compounds (100 MUg in 15
      MUl). The technology can be scaled so that multiple bilayers can be addressed,
      providing a screening platform for ion channels, transporters, and nanopores. 

PMID- 25610516
TI  - Centrifugal multiplexing fixed-volume dispenser on a plastic lab-on-a-disk for
      parallel biochemical single-end-point assays.
AB  - In this study, a multiple sample dispenser for precisely metered fixed volumes
      was successfully designed, fabricated, and fully characterized on a plastic
      centrifugal lab-on-a-disk (LOD) for parallel biochemical single-end-point assays.
      The dispenser, namely, a centrifugal multiplexing fixed-volume dispenser (C
      MUFID) was designed with microfluidic structures based on the theoretical
      modeling about a centrifugal circumferential filling flow. The designed LODs were
      fabricated with a polystyrene substrate through micromachining and they were
      thermally bonded with a flat substrate. Furthermore, six parallel metering and
      dispensing assays were conducted at the same fixed-volume (1.27 MUl) with a
      relative variation of +/-0.02 MUl. Moreover, the samples were metered and
      dispensed at different sub-volumes. To visualize the metering and dispensing
      performances, the C-MUFID was integrated with a serpentine micromixer during
      parallel centrifugal mixing tests. Parallel biochemical single-end-point assays
      were successfully conducted on the developed LOD using a standard serum with
      albumin, glucose, and total protein reagents. The developed LOD could be widely
      applied to various biochemical single-end-point assays which require different
      volume ratios of the sample and reagent by controlling the design of the C-MUFID.
      The proposed LOD is feasible for point-of-care diagnostics because of its mass
      producible structures, reliable metering/dispensing performance, and parallel
      biochemical single-end-point assays, which can identify numerous biochemical. 

PMID- 25610517
TI  - 3D printed microfluidic devices with integrated valves.
AB  - We report the successful fabrication and testing of 3D printed microfluidic
      devices with integrated membrane-based valves. Fabrication is performed with a
      low-cost commercially available stereolithographic 3D printer. Horizontal
      microfluidic channels with designed rectangular cross sectional dimensions as
      small as 350 MUm wide and 250 MUm tall are printed with 100% yield, as are
      cylindrical vertical microfluidic channels with 350 MUm designed (210 MUm actual)
      diameters. Based on our previous work [Rogers et al., Anal. Chem. 83, 6418
      (2011)], we use a custom resin formulation tailored for low non-specific protein
      adsorption. Valves are fabricated with a membrane consisting of a single build
      layer. The fluid pressure required to open a closed valve is the same as the
      control pressure holding the valve closed. 3D printed valves are successfully
      demonstrated for up to 800 actuations. 

PMID- 25610518
TI  - Simple and easy surgical technique for infantile hemangiomas: intralesional
      excision and primary closure.
AB  - OBJECTIVE: Infantile hemangioma (IH) is a benign vascular tumor that gradually
      shrinks over several years. Involuting or involuted IHs usually retain their
      shape, however, and result in redundant skin or conspicuous scarring due to
      ulceration in the proliferating phase. We present a case series of 12 patients
      who underwent intralesional excision and primary closure for treatment of
      involuting or involuted IH. METHODS: Twelve patients (5 boys, 7 girls) underwent
      our treatment method for involuting or involuted IH. A blinded assessor evaluated
      clinical result of each patient. RESULTS: Surgical results were excellent in 4
      patients, good in 6, and fair in 2. A small dog ear was prominent in 1 patient;
      nevertheless, all parents were satisfied with the results. CONCLUSIONS:
      Intralesional excision and primary closure for treatment of involuting or
      involuted IH is an easy and simple procedure that does not result in dog-ear
      formation or elongated residual scarring.

PMID- 25610519
TI  - Non-allergenic factors from pollen modulate T helper cell instructing notch
      ligands on dendritic cells.
AB  - BACKGROUND: Pollen allergens are delivered to epithelial surfaces of the upper
      respiratory tract in conjunction with multiple endogenous adjuvants. We
      previously demonstrated pollen-mediated modulation of cytokine and chemokine
      production of dendritic cells, contributing to a Th2-dominated micromilieu. As T
      helper cell differentiation not only depends on dendritic cell-derived cytokines
      but also on cell-cell-contact mediated mechanisms, we studied the expression of
      notch ligands and myeloid differentiation primary response protein 88 (MyD88) in
      dendritic cells matured in the presence of aqueous birch pollen extracts and
      pollen-associated E1-phytoprostanes. METHODS: Human monocyte-derived dendritic
      cells were stimulated with aqueous birch pollen extracts in the absence or
      presence of lipopolysaccharide, and mRNA expression levels of notch ligands delta
      1 and -4, jagged-1 and -2 and of myd88 were determined. Regulation of Delta-4 and
      MyD88 by aqueous pollen extracts was assessed on protein level. The contribution
      of notch signaling to T helper cell differentiation was analyzed in allogeneic T
      cell stimulation assays. RESULTS: In immature dendritic cells, stimulation with
      pollen extracts resulted in an induction of both delta and jagged notch ligands.
      The lipopolysaccharide-induced up-regulation of delta-1 and -4 and of myd88 was
      decreased by aqueous pollen extracts, whereas jagged expression was induced.
      Reduction of Delta-4 and MyD88 by aqueous pollen extracts was confirmed on
      protein level. The Th2-skewing activity was contained in a fraction of aqueous
      pollen extracts enriched for molecules <3 kDa and was distinct from the
      previously identified E1-phytoprostanes. Reduction of notch signaling in
      dendritic cells matured in the presence aqueous pollen extract leads to
      inhibition of IL-10 and to induction of IL-5 production in naive T cells
      differentiated by these dendritic cells. CONCLUSIONS: Pollen derived, non
      allergenic factors reduce the dendritic cell's expression of Th1 instructing
      Delta-like notch ligands and of MyD88, thereby promoting Th2 skewing of T helper
      cell responses.

PMID- 25610520
TI  - Papular scars: an addition to the acne scar classification scheme.

PMID- 25610521
TI  - Efficacy, safety, and subject satisfaction of a specified skin care regimen to
      cleanse, medicate, moisturize, and protect the skin of patients under treatment
      for acne vulgaris.
AB  - Optimal management of acne vulgaris requires incorporation of several components
      including patient education, selection of a rational therapeutic regimen,
      dedicated adherence with the program by the patient, and integration of proper
      skin care. Unfortunately, the latter component is often overlooked or not
      emphasized strongly enough to the patient. Proper skin care may reduce potential
      irritation that can be associated with topical acne medications and prevents the
      patient from unknowingly using skin care products that can actually sabotage
      their treatment. This article reviews the effectiveness, skin tolerability,
      safety, and patient satisfaction of an open label study in which a specified skin
      care regimen is used in combination with topical therapy. The study was designed
      to mirror "real world" management of facial acne vulgaris clinical practice. The
      skin care regimen used in this study included a brand foam wash and a brand
      moisturizer with SPF 30 photoprotection, both of which contain ingredients that
      are included to provide benefits for acne-prone and acne-affected skin. 

PMID- 25610522
TI  - Comparative efficacy and tolerability of dapsone 5% gel in adult versus
      adolescent females with acne vulgaris.
AB  - OBJECTIVE: To determine whether the response to dapsone 5% gel was similar in
      adolescent girls and adult women with facial acne vulgaris. DESIGN AND SETTING:
      Subgroup analysis of female subjects with acne vulgaris receiving active
      treatment enrolled in two randomized, double-blind Phase 3 clinical trials.
      TREATMENT: Twice-daily applications of dapsone 5% gel over 12 weeks.
      PARTICIPANTS: Adolescent (12-17 years of age) and adult (>=18 years of age)
      females. MEASUREMENTS: At baseline and at Weeks 2,4,6,8, and 12, subjects were
      evaluated using the global acne assessment score and by counts of inflammatory,
      noninflammatory, and total acne vulgaris lesions. Adverse events were monitored.
      RESULTS: A total of 347 adolescent and 434 adult women were included in the
      subgroup analysis. At Week 12, dapsone 5% gel significantly reduced mean global
      acne assessment score in both subgroups (p<0.001); however, the proportion of
      subjects with clinical success (no or minimal acne based on global acne
      assessment score) at Week 12 was greater in adult women (53.5%) versus adolescent
      females (45.3%, p=0.022). Significantly greater percentage reductions in both
      noninflammatory (p<0.0001) and total lesion counts (p=0.0008) were observed in
      the adult group as compared to the adolescent group. Percentage reductions from
      baseline in inflammatory lesions were similar in both groups. No major safety
      issues and no previously unrecognized safety signals were noted. CONCLUSION: This
      subgroup analysis of female patients indicates that dapsone 5% gel twice daily is
      effective in reducing inflammatory and noninflammatory acne vulgaris lesions in
      both adolescent and adult women, and is safe in these subgroups. Overall, these
      data suggest that efficacy of dapsone 5% gel twice daily for facial acne vulgaris
      may be greater in the adult female population.

PMID- 25610523
TI  - Calcium hydroxylapatite: over a decade of clinical experience.
AB  - BACKGROUND: Calcium hydroxylapatite is one of the most well-studied dermal
      fillers worldwide and has been extensively used for the correction of moderate-to
      severe facial lines and folds and to replenish lost volume. OBJECTIVES: To mark
      the milestone of 10 years of use in the aesthetic field, this review will
      consider the evolution of calcium hydroxylapatite in aesthetic medicine, provide
      a detailed injection protocol for a global facial approach, and examine how the
      unique properties of calcium hydroxylapatite provide it with an important place
      in today's market. METHODS: This article is an up-to-date review of calcium
      hydroxylapatite in aesthetic medicine along with procedures for its use,
      including a detailed injection protocol for a global facial approach by three
      expert injectors. CONCLUSION: Calcium hydroxylapatite is a very effective agent
      for many areas of facial soft tissue augmentation and is associated with a high
      and well-established safety profile. Calcium hydroxylapatite combines high
      elasticity and viscosity with an ability to induce long-term collagen formation
      making it an ideal agent for a global facial approach.

PMID- 25610525
TI  - Stresses, aging, and age-related disorders.

PMID- 25610524
TI  - Atrophic acne scarring: a review of treatment options.
AB  - BACKGROUND: Scarring is an unfortunate and frequent complication of acne,
      resulting in significant psychological distress for patients. Fortunately,
      numerous treatment options exist for acne scarring. OBJECTIVES: To extensively
      review the literature on treatment options for atrophic acne scarring. MATERIALS
      AND METHODS: A comprehensive literature search was conducted on the following
      topics: dermabrasion, subcision, punch techniques, chemical peels, tissue
      augmentation, and lasers. RESULTS: The literature supports the use of various
      treatment modalities; superior results may be achieved when multiple modalities
      are combined for a multi-step approach to scarring. CONCLUSION: The safety and
      efficacy of various treatment devices for acne scarring is well established, but
      there is a paucity of split-face trials comparing modalities.

PMID- 25610526
TI  - Maintaining medication quality.

PMID- 25610527
TI  - Budgetary Impact of Adding Riociguat to a US Health Plan for the Treatment of
      Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary
      Hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic
      pulmonary hypertension (CTEPH) are chronic, debilitating, and life-threatening
      conditions. Riociguat is the first and only pharmacotherapy approved by the US
      Food and Drug Administration (FDA) for the treatment of PAH and for CTEPH in
      patients who are either inoperable or have persistent pulmonary hypertension
      after surgery. OBJECTIVE: To estimate the budgetary impact of adding riociguat to
      a US health plan's formulary for the treatment of patients with PAH or CTEPH
      using a budget impact analytic model. METHODS: A customizable, Microsoft Excel
      based decision analytic tool was developed to estimate the impact of riociguat on
      per-member per-month (PMPM) and per-member per-year (PMPY) bases in Medicare and
      non-Medicare health plans. The economic impact was calculated based on 1 million
      insured lives, published prevalence estimates of PAH and CTEPH, pharmacotherapy
      eligible patients with PAH or CTEPH, administration costs, and monitoring costs
      related to pharmacotherapy. The drug costs were based on wholesale acquisition
      costs, and the medical costs were derived from Truven Health MarketScan claims
      data and the Medicare 2013 Clinical Diagnostic Laboratory Fee Schedule and
      Physician Fee Schedule. The market share for approved treatments was based on a
      tracking study of physicians treating patients with PAH or CTEPH. A sensitivity
      analysis was used to test the model's robustness. RESULTS: In a hypothetical plan
      population of 1 million members, the model estimated that 7 patients with PAH and
      2 patients with CTEPH would be suitable for pharmacotherapy. Overall, 3 patients
      (1 with PAH and 2 with CTEPH) were receiving riociguat in a health plan
      consisting of patients with commercial and with Medicare insurance coverage. The
      incremental PMPY and PMPM costs for providing insurance coverage for riociguat
      were $0.27 and $0.02, respectively, for non-Medicare and Medicare health plans.
      Sensitivity analyses indicated that the budget impact increased by $0.01 PMPM,
      with a 25% increase in base-case parameter values. CONCLUSION: Riociguat is a
      first-in-class and the only FDA-approved treatment for patients with PAH or CTEPH
      2 debilitating, chronic, and life-threatening conditions with poor prognosis.
      This drug offers health plans an effective and safe treatment option, with a
      minimal economic impact. The financial impact to a health plan of providing
      coverage for riociguat in the first year of treatment was as low as $0.02 PMPM.
      The real-world budget impact of riociguat needs to be measured using real-world
      evidence to validate our results.

PMID- 25610528
TI  - Diagnosis and treatment of bipolar disorders in adults: a review of the evidence
      on pharmacologic treatments.
AB  - BACKGROUND: Patients with bipolar disorder are exceptionally challenging to
      manage because of the dynamic, chronic, and fluctuating nature of their disease.
      Typically, the symptoms of bipolar disorder first appear in adolescence or early
      adulthood, and are repeated over the patient's lifetime, expressed as
      unpredictable recurrences of hypomanic/manic or depressive episodes. The lifetime
      prevalence of bipolar disorder in adults is reported to be approximately 4%, and
      its management was estimated to cost the US healthcare system in 2009 $150
      billion in combined direct and indirect costs. OBJECTIVE: To review the published
      literature and describe the personal and societal burdens associated with bipolar
      disorder, the impact of delays in accurate diagnosis, and the evidence for the
      clinical effectiveness of available pharmacologic therapies. METHODS: The studies
      in this comprehensive review were selected for inclusion based on clinical
      relevance, importance, and robustness of data related to diagnosis and treatment
      of bipolar disorder. The search terms that were initially used on MEDLINE/PubMed
      and Google Scholar were restricted to 1994 through 2014 and included "bipolar
      disorder," "mania," "bipolar depression," "mood stabilizer," "atypical
      antipsychotics," and "antidepressants." High-quality, recent reviews of major
      relevant topics were included to supplement the primary studies. DISCUSSION:
      Substantial challenges facing patients with bipolar disorder, in addition to
      their severe mood symptoms, include frequent incidence of psychiatric (eg,
      anxiety disorders, alcohol or drug dependence) and general medical comorbidities
      (eg, diabetes, cardiovascular disease, obesity, migraine, and hepatitis C virus
      infection). It has been reported that more than 75% of patients take their
      medication less than 75% of the time, and the rate of suicide (0.4%) among
      patients with bipolar disorder is more than 20 times greater than in the general
      US population. Mood stabilizers are the cornerstone of treatment of bipolar
      disorder, but atypical antipsychotics are broadly as effective; however,
      differences in efficacy exist between individual agents in the treatment of the
      various phases of bipolar disorder, including treatment of acute mania or acute
      depression symptoms, and in the prevention of relapse. CONCLUSION: The challenges
      involved in managing bipolar disorder over a patient's lifetime are the result of
      the dynamic, chronic, and fluctuating nature of this disease. Diligent selection
      of a treatment that takes into account its efficacy in the various phases of the
      disorder, along with the safety profile identified in clinical trials and in the
      real world can help ameliorate the impact of this devastating condition.

PMID- 25610529
TI  - Chondroprotective Effect of Kartogenin on CD44-Mediated Functions in Articular
      Cartilage and Chondrocytes.
AB  - OBJECTIVE: A recent report identified the small molecule kartogenin as a
      chondrogenic and chondroprotective agent. Since changes in hyaluronan metabolism
      occur during cartilage degeneration in osteoarthritis, we began studies to
      determine whether there was a connection between extracellular hyaluronan, CD44
      hyaluronan interactions and the effects of kartogenin on articular chondrocytes.
      METHODS: Chondrocytes cultured in monolayers, bioengineered neocartilages, or
      cartilage explants were treated with kartogenin with or without stimulation by IL
      1beta. Accumulation of matrix was visualized by a particle exclusion assay or by
      safranin O staining and release of sulfated glycosaminoglycans was determined.
      Production of aggrecanases and aggrecan G1-ITEGE neoepitope, fragmentation of
      CD44 and the SMAD1/5/8 signaling pathway were evaluated by western blotting.
      RESULTS: Kartogenin treatment enhanced chondrocyte pericellular matrix assembly
      and retention in the presence of IL-1beta. The chondroprotective effects of
      kartogenin on IL-1beta-induced release of sulfated glycosaminoglycans from
      articular cartilage explants, reduction in safranin O staining of neocartilage
      discs as well as a reduction in aggrecan G1-ITEGE neoepitope in chondrocyte and
      explant cartilage cultures were observed. Kartogenin partially blocked the IL
      1beta-induced increased expression of ADAMTS-5. Additionally, kartogenin-treated
      articular chondrocytes exhibited a decrease in CD44 proteolytic fragmentation.
      However, kartogenin treatment did not enhance proteoglycan in control, non-IL
      1beta-treated cultures. Similarly, kartogenin enhanced the SMAD1 phosphorylation
      but only following pretreatment with IL-1beta. CONCLUSION: These studies provide
      novel information on the chondroprotective function of kartogenin in adult
      articular cartilage. The effects of kartogenin are significant after activation
      of chondrocytic chondrolysis, which may occur following disruption of homeostasis
      maintained by hyaluronan-CD44 interactions.

PMID- 25610530
TI  - Role of endoscopy in management of gastrointestinal complications of portal
      hypertension.
AB  - The management of patients with gastrointestinal complications of portal
      hypertension is often complex and challenging. The endoscopy plays an important
      role in the management of these patients. The role of endoscopy is both
      diagnostic and interventional and in the last years the techniques have undergone
      a rapid expansion with the advent of different and novel endoscopic modalities,
      with consequent improvement of investigation and treatment of these patients. The
      choice of best therapeutic strategy depends on many factors: baseline disease,
      patient's clinical performance and the timing when it is done if in emergency or
      a prophylactic approaches. In this review we evaluate the endoscopic management
      of patients with the gastrointestinal complications of portal hypertension. 

PMID- 25610532
TI  - Endoscopic ultrasound-guided biliary drainage as an alternative to percutaneous
      drainage and surgical bypass.
AB  - Endoscopic retrograde cholangiopancreatography had been a treatment modality of
      choice for both benign and malignant biliary tract obstruction for more than half
      century, with a very high clinical success rate and low complications. But in
      certain circumstances, such as advanced and locally advanced pancreatobiliary
      malignancies (pancreatic cancer, cholangiocarcinoma, ampullary tumor) and tight
      benign strictures, endoscopic retrograde cholangiopancreatography (ERCP) fails.
      Up to this point, the only alternative interventions for these conditions were
      percutaneous transhepatic biliary drainage or surgery. Endoscopic ultrasound
      guided interventions was introduced for a couple decades with the better
      visualization and achievement of the pancreatobiliary tract. And it's still in
      the process of ongoing development. The inventions of new techniques and
      accessories lead to more feasibility of high-ended procedures. Endoscopic
      ultrasound guided biliary drainage was a novel treatment modality for the patient
      who failed ERCP with the less invasive technique comparing to surgical bypass.
      The technical and clinical success was high with acceptable complications.
      Regarded the ability to drain the biliary tract internally without an exploratory
      laparotomy, this treatment modality became a very interesting procedures for many
      endosonographers, worldwide, in a short period. We have reviewed the literature
      and suggest that endoscopic ultrasound-guided biliary drainage is also an option,
      and one with a high probability of success, for biliary drainage in the patients
      who failed conventional endoscopic drainage. 

PMID- 25610533
TI  - Self-expandable metal stents for achalasia: Thinking out of the box!
AB  - Achalasia is a primary motor disorder of the esophagus diagnosed manometrically
      in the clinical setting of dysphagia to both solids and liquids. Currently
      established treatment options include pneumatic dilation, laparoscopic Heller
      myotomy, botulinum toxin injection performed endoscopically, oral agents that
      relax the lower esophageal sphincter and esophagectomy for refractory, end-stage
      disease. Despite their effectiveness, a significant proportion of patients
      eventually relapses and needs retreatment. In this setting, several new
      techniques are under investigation promising future enrichment of our therapeutic
      armamentarium for achalasic patients. Among them, peroral endoscopic myotomy and
      self-expandable metal stents placed across the gastro-esophageal junction
      represent the most encouraging modalities, as initial studies assessing their
      efficacy and safety indicate. This review highlights the role of self-expandable
      metal stents in the management of patients with achalasia. Their possible
      position in the therapeutic algorithm of achalasia along with established and
      novel techniques is also assessed. Finally, the need for large prospective
      randomized trials is underlined in order to elucidate the numerous relevant
      issues. 

PMID- 25610534
TI  - Intragastric surgery using laparoscopy and oral endoscopy for gastric submucosal
      tumors.
AB  - We review the techniques and outcomes of the intragastric resection for gastric
      submucosal tumors (GSTs) using laparoscope and oral endoscope. In the literature,
      the mean operation time, intraoperative blood loss, pathological size of the
      tumor and postoperative hospital stay were 134 min, minimal, 31 mm and 6.4 d,
      respectively. There were no particular perioperative complications during the
      follow-up period (mean: 121.3 mo). Intragastric surgery using laparoscopy and
      oral endoscopy can be considerably beneficial for patients with GSTs locating in
      the upper third of the stomach between 2-5 cm in diameter and < 8 cm(2) in cross
      sectional area and located in the upper third of the stomach. 

PMID- 25610535
TI  - Current status of single-balloon enteroscopy: Insertability and clinical
      applications.
AB  - The single-balloon enteroscopy (SBE) system was launched in 2007, proposed as a
      simpler method than double-balloon enteroscopy (DBE). Controversy surrounds
      whether the SBE system has the same insertability as DBE. However, many methods
      have been proposed to improve the depth of insertion with the SBE system,
      involving several techniques and endoscopic accessories. SBE is used for
      investigating not only small bowel diseases, but also diseases of the
      pancreatobiliary and colonic structures. SBE is a necessary advancement for many
      endoscopic procedures and applications in modern clinical practice. In our
      review, we summarized the current literature concerning the insertability of SBE
      and described the technical aspects of improving the rate of deep insertion in
      SBE procedures. In addition, the recent applications of SBE to diseases besides
      those of the small bowel are described. 

PMID- 25610531
TI  - Small bowel capsule endoscopy: Where are we after almost 15 years of use?
AB  - The development of capsule endoscopy (CE) in 2001 has given gastroenterologists
      the opportunity to investigate the small bowel in a non-invasive way. CE is most
      commonly performed for obscure gastrointestinal bleeding, but other indications
      include diagnosis or follow-up of Crohn's disease, suspicion of a small bowel
      tumor, diagnosis and surveillance of hereditary polyposis syndromes, Nonsteroidal
      anti-inflammatory drug-induced small bowel lesions and celiac disease. Almost
      fifteen years have passed since the release of the small bowel capsule. The
      purpose of this review is to offer the reader a brief but complete overview on
      small bowel CE anno 2014, including the technical and procedural aspects, the
      possible complications and the most important indications. We will end with some
      future perspectives of CE. 

PMID- 25610536
TI  - Treatment of dysplastic Barrett's Oesophagus in lower volume centres after
      structured training.
AB  - AIM: To investigate whether dysplastic Barrett's Oesophagus can be safely and
      effectively treated endoscopically in low volume centres after structured
      training. METHODS: After attending a structured training program in Amsterdam on
      the endoscopic treatment of dysplastic Barrett's Oesophagus, treatment of these
      patients was initiated at St Marys Hospital. This is a retrospective case series
      conducted at a United Kingdom teaching Hospital, of patients referred for
      endoscopic treatment of Barrett's oesophagus with high grade dysplasia or early
      cancer, who were diagnosed between January 2008 and February 2012. Data was
      collected on treatment provided (radiofrequency ablation and endoscopic
      resection), and success of treatment both at the end of treatment and at follow
      up. Rates of immediate and long term complications were assessed. RESULTS: Thirty
      two patients were referred to St Marys with high grade dysplasia or intramucosal
      cancer within a segment of Barrett's Oesophagus. Twenty-seven met the study
      inclusion criteria, 16 of these had a visible nodule at initial endoscopy.
      Treatment was given over a median of 5 mo, and patients received a median of 3
      treatment sessions over this time. At the end of treatment dysplasia was
      successfully eradicated in 96% and intestinal metaplasia in 88%, on per protocol
      analysis. Patients were followed up for a median of 18 mo. At which time complete
      eradication of dysplasia was maintained in 86%. Complications were rare: 2
      patients suffered from post-procedural bleeding, 4 cases were complicated by
      oesophageal stenosis. Recurrence of cancer was seen in 1 case. CONCLUSION: With
      structured training good outcomes can be achieved in low volume centres treating
      dysplastic Barrett's Oesophagus.

PMID- 25610537
TI  - Russell body duodenitis with immunoglobulin kappa light chain restriction.
AB  - Russell bodies are eosinophilic intracytoplasmic globules which are likely the
      result of disturbed secretion of immunoglobulins that accumulate within the
      plasma cell. Russell body collections have been identified within the stomach,
      known as Russell body gastritis. Similar lesions within the duodenum are referred
      to as Russell body duodenitis, which is rare. Several Russell body gastritis case
      reports are associated with Helicobacter pylori. However, the etiology of Russell
      body duodenitis remains unclear. Here we report the first case of Russell body
      duodenitis with immunoglobulin light chain restriction in a background of peptic
      duodenitis. 

PMID- 25610538
TI  - Role of radiotherapy in the pre-operative management of carcinoma of the
      esophagus.
AB  - The use of radiotherapy in the management of carcinoma of the esophagus and
      gastro-esophageal junction has undergone much evolution over the past 2 decades.
      Advances to define its role have been slow with meta-analyses often providing the
      most useful data. In spite of this many institutions around the world are divided
      about the role of radiotherapy in this disease and attribute different roles to
      radiotherapy based on clinical stage, tumor site and histology. The purpose of
      this review is to try to define the role of radiotherapy given our current
      knowledge base and to review which current and future trials may fill the gaps of
      knowledge that we currently have. It will also highlight the difficulties in
      making firm recommendations about the use of radiotherapy especially in a time
      when technology and treatments are rapidly evolving. 

PMID- 25610539
TI  - Angular scale expansion theory and the misperception of egocentric distance in
      locomotor space.
AB  - Perception is crucial for the control of action, but perception need not be
      scaled accurately to produce accurate actions. This paper reviews evidence for an
      elegant new theory of locomotor space perception that is based on the dense
      coding of angular declination so that action control may be guided by richer
      feedback. The theory accounts for why so much direct-estimation data suggests
      that egocentric distance is underestimated despite the fact that action measures
      have been interpreted as indicating accurate perception. Actions are calibrated
      to the perceived scale of space and thus action measures are typically unable to
      distinguish systematic (e.g., linearly scaled) misperception from accurate
      perception. Whereas subjective reports of the scaling of linear extent are
      difficult to evaluate in absolute terms, study of the scaling of perceived angles
      (which exist in a known scale, delimited by vertical and horizontal) provides new
      evidence regarding the perceptual scaling of locomotor space.

PMID- 25610540
TI  - Karyotype, C-banding and AgNORs of two endemic leuciscine fish,
      Pseudophoxinuscrassus (Ladiges, 1960) and P.hittitorum Freyhof & Ozulug, 2010
      (Teleostei, Cyprinidae).
AB  - The genus Pseudophoxinus Bleeker, 1860 is found in a wide range of habitats in
      central Anatolia, but it is not well known from a cytogenetic aspect. In this
      study the first karyotypic description of the spring minnows
      Pseudophoxinuscrassus (Ladiges, 1960) and Pseudophoxinushittitorum Freyhof &
      Ozulug, 2010 by means of conventional methods (Giemsa staining, C-banding, silver
      nitrate impregnation (Ag-NORs)) was performed. Both species are endemic and have
      restricted distributions in Central Anatolia. Pseudophoxinuscrassus and
      Pseudophoxinushittitorum have the same diploid chromosome number, 2n = 50,
      patterns of distribution of constitutive heterochromatin (CH), and localization
      of nucleolus organizer regions (NORs), but differ in their karyotypic formulae
      (KFs). The C-banding technique revealed clear pericentromeric blocks of CH in
      many chromosomes; Ag-NORs treatment revealed consistent positive signals at the
      end of the short arms of a submetacentric chromosome pair, likely homologous in
      both species. The karyotypic differences found between these species can be used
      for their taxonomical study. 

PMID- 25610541
TI  - Karyotype rearrangements and telomere analysis in Myzuspersicae (Hemiptera,
      Aphididae) strains collected on Lavandula sp. plants.
AB  - Karyotype analysis of nine strains of the peach-potato aphid Myzuspersicae
      (Sulzer, 1776), collected on Lavandula sp. plants, evidenced showed that five of
      them had a standard 2n = 12 karyotype, one possessed a fragmentation of the X
      chromosome occurring at the telomere opposite to the NOR-bearing one and three
      strains had a chromosome number 2n = 11 due to a non-reciprocal translocation of
      an autosome A3 onto an A1 chromosome. Interestingly, the terminal portion of the
      autosome A1 involved in the translocation was the same in all the three strains,
      as evidenced by FISH with the histone cluster as a probe. The study of telomeres
      in the Myzuspersicae strain with the X fission evidenced that telomerase
      synthesised de novo telomeres at the breakpoints resulting in the stabilization
      of the chromosomal fragments. Lastly, despite the presence of a conserved
      telomerase, aphid genome is devoid of genes coding for shelterin, a complex of
      proteins involved in telomere functioning frequently reported as conserved in
      eukaryotes. The absence of this complex, also confirmed in the genome of other
      arthropods, suggests that the shift in the sequence of the telomeric repeats has
      been accompanied by other changes in the telomere components in arthropods in
      respect to other metazoans. 

PMID- 25610542
TI  - Chromosome number evolution in skippers (Lepidoptera, Hesperiidae).
AB  - Lepidoptera (butterflies and moths), as many other groups of animals and plants,
      simultaneously represent preservation of ancestral karyotype in the majority of
      families with a high degree of chromosome number instability in numerous
      independently evolved phylogenetic lineages. However, the pattern and trends of
      karyotype evolution in some Lepidoptera families are poorly studied. Here I
      provide a survey of chromosome numbers in skippers (family Hesperiidae) based on
      intensive search and analysis of published data. I demonstrate that the majority
      of skippers preserve the haploid chromosome number n=31 that seems to be an
      ancestral number for the Hesperiidae and the order Lepidoptera at whole. However,
      in the tribe Baorini the derived number n=16 is the most typical state which can
      be used as a (syn)apomorphic character in further phylogenetic investigations.
      Several groups of skippers display extreme chromosome number variations on within
      species (e.g. the representatives of the genus Carcharodus Hubner, [1819]) and
      between-species (e.g. the genus Agathymus Freeman, 1959) levels. Thus, these
      groups can be used as model systems for future analysis of the phenomenon of
      chromosome instability. Interspecific chromosomal differences are also shown to
      be useful for discovering and describing new cryptic species of Hesperiidae
      representing in such a way a powerful tool in biodiversity research. Generally,
      the skipper butterflies promise to be an exciting group that will significantly
      contribute to the growing knowledge of patterns and processes of chromosome
      evolution. 

PMID- 25610543
TI  - First karyotype data on the family Myerslopiidae (Hemiptera, Auchenorrhyncha,
      Cicadomorpha).
AB  - In the first cytogenetic study of the recently proposed family Myerslopiidae the
      male karyotype of Mapucheachilensis (Nielson, 1996) was analyzed using
      conventional chromosome staining, AgNOR- and C-bandings, and fluorescence in situ
      hybridization (FISH) with 18S rDNA and (TTAGG) n telomeric probes. A karyotype of
      2n = 16 + XY, NOR on a medium-sized pair of autosomes, subterminal location of C
      heterochromatin, and presence of (TTAGG) n telomeric sequence were determined.
      Additionally, the male internal reproductive system was studied. 

PMID- 25610544
TI  - Karyotype diversity and patterns of chromosomal evolution in Eigenmannia
      (Teleostei, Gymnotiformes, Sternopygidae).
AB  - Conventional (Giemsa, C-banding, Ag - NORs) and molecular [5S rDNA, 18S rDNA,
      (TTAGGG)n] cytogenetic techniques were employed to study six species of the genus
      Eigenmannia Jordan & Evermann, 1896. They exhibited diploid chromosome numbers
      ranging from 2n=28 (Eigenmannia sp.1) to 2n=38 (Eigenmanniavirescens
      (Valenciennes, 1836)). The C-banding results revealed that species with the
      lowest 2n have less heterochromatin content and that morphologically
      differentiated sex chromosomes observed in two species showed distinct patterns
      of heterochromatin. While the X1, X2 and Y-chromosomes of Eigenmannia sp.2 showed
      only centromeric heterochromatin, the XY sex chromosomes of Eigenmanniavirescens
      possessed large heterochromatic blocks in the terminal position, particularly on
      the X chromosome. The nucleolus organizer regions (NORs) were located in
      different positions when compared to the 5S rDNA sites. Additionally, the
      presence of minor ribosomal gene sites on the sex chromosome pair of
      Eigenmanniavirescens represented a new type of the sex chromosomes in this group.
      The telomeric probe (TTAGGG)n hybridized to the terminal portion of all
      chromosomes in all species examined however, interstitial telomeric sites were
      found in the metacentric pair No. 2 in Eigenmannia sp.1. The analyzes confirmed
      some hypotheses about karyotype evolution in the genus Eigenmannia, and brought
      new information about the distribution of the genetic material in the chromosomes
      of the samples analyzed providing new insights for understanding the process
      differentiation in the genomes of species under study. 

PMID- 25610545
TI  - Taxonomic position of several enigmatic Polyommatus (Agrodiaetus) species
      (Lepidoptera, Lycaenidae) from Central and Eastern Iran: insights from molecular
      and chromosomal data.
AB  - The species-rich subgenus Polyommatus (Agrodiaetus) has become one of the best
      studied groups of Palearctic blue butterflies (Lepidoptera, Lycaenidae). However,
      the identity and phylogenetic position of some rare taxa from Iran have remained
      unclear. An enigmatic, recently described Central Iranian species Polyommatus
      (Agrodiaetus) shirkuhensis ten Hagen et Eckweiler, 2001 has been considered as a
      taxon closely related either to Polyommatus (Agrodiaetus) eckweileri ten Hagen,
      1998 or to Polyommatus (Agrodiaetus) baltazardi (de Lesse, 1962). Polyommatus
      (Agrodiaetus) baltazardi, in its turn, was treated as a taxon close to Iranian
      Pakistani Polyommatus (Agrodiaetus) bogra Evans, 1932. Here we used a combination
      of molecular and chromosomal markers to show that none of these hypotheses was
      true. Instead, Polyommatus (Agrodiaetus) shirkuhensis was recovered as a member
      of a species group close to Polyommatus (Agrodiaetus) cyaneus (Staudinger, 1899).
      From genetically closest species, Polyommatus (Agrodiaetus) kermansis (de Lesse,
      1962), Polyommatus (Agrodiaetus) cyaneus and Polyommatus (Agrodiaetus)
      sennanensis (de Lesse, 1959), it differs by the wing coloration. From
      morphologically similar Polyommatus (Agrodiaetus) mofidii (de Lesse, 1963) and
      Polyommatus (Agrodiaetus) sorkhensis Eckweiler, 2003, it differs by its
      chromosome number, n=21. Polyommatus (Agrodiaetus) bogra and Polyommatus
      (Agrodiaetus) baltazardi were found to be members of two different species groups
      and, thus, are not closely related. 

PMID- 25610546
TI  - Use of laser microdissection for the construction of Humulusjaponicus Siebold et
      Zuccarini, 1846 (Cannabaceae) sex chromosome-specific DNA library and
      cytogenetics analysis.
AB  - Dioecy is relatively rare among plant species, and distinguishable sex
      chromosomes have been reported in few dioecious species. The multiple sex
      chromosome system (XX/XY1Y2) of Humulusjaponicus Siebold et Zuccarini, 1846
      differs from that of other members of the family Cannabaceae, in which the XX/XY
      chromosome system is present. Sex chromosomes of Humulusjaponicus were isolated
      from meiotic chromosome spreads of males by laser microdissection with the
      P.A.L.M. MicroLaser system. The chromosomal DNA was directly amplified by
      degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). Fast
      fluorescence in situ hybridization (FAST-FISH) using a labeled, chromosome
      specific DOP-PCR product as a probe showed preferential hybridization to sex
      chromosomes. In addition, the DOP-PCR product was used to construct a short
      insert, Humulusjaponicus sex chromosomes-specific DNA library. The randomly
      sequenced clones showed that about 12% of them have significant homology to
      Humuluslupulus and 88% to Cannabissativa Linnaeus, 1753 sequences from GenBank
      database. Forty-four percent of the sequences show homology to plant
      retroelements. It was concluded that laser microdissection is a useful tool for
      isolating the DNA of sex chromosomes of Humulusjaponicus and for the construction
      of chromosome-specific DNA libraries for the study of the structure and evolution
      of sex chromosomes. The results provide the potential for identifying unique or
      sex chromosome-specific sequence elements in Humulusjaponicus and could aid in
      the identification of sex chromosome-specific repeat and coding regions through
      chromosome isolation and genome complexity reduction. 

PMID- 25610547
TI  - A proposal for a multivariate quantitative approach to infer karyological
      relationships among taxa.
AB  - Until now, basic karyological parameters have been used in different ways by
      researchers to infer karyological relationships among organisms. In the present
      study, we propose a standardized approach to this aim, integrating six different,
      not redundant, parameters in a multivariate PCoA analysis. These parameters are
      chromosome number, basic chromosome number, total haploid chromosome length, MCA
      (Mean Centromeric Asymmetry), CVCL (Coefficient of Variation of Chromosome
      Length) and CVCI (Coefficient of Variation of Centromeric Index). The method is
      exemplified with the application to several plant taxa, and its significance and
      limits are discussed in the light of current phylogenetic knowledge of these
      groups. 

PMID- 25610548
TI  - Karyotype diversity among predatory Reduviidae (Heteroptera).
AB  - Species of infraorder Cimicomorpha of Heteroptera exhibit holokinetic chromosomes
      with inverted meiosis for sex chromosomes and high variation in chromosome
      number. The family Reduviidae, which belongs to this infraorder, is also
      recognized by high variability of heterochromatic bands and chromosome location
      of 18S rDNA loci. We studied here five species of Reduviidae (Harpactorinae) with
      predator habit, which are especially interesting because individuals are found
      solitary and dispersed in nature. These species showed striking variation in
      chromosome number (including sex chromosome systems), inter-chromosomal
      asymmetry, different number and chromosome location of 18S rDNA loci, dissimilar
      location and quantity of autosomal C-heterochromatin, and different types of
      repetitive DNA by fluorochrome banding, probably associated with occurrence of
      different chromosome rearrangements. Terminal chromosome location of C
      heterochromatin seems to reinforce the model of equilocal dispersion of
      repetitive DNA families based in the "bouquet configuration". 

PMID- 25610549
TI  - Karyotypic variation in the Andean rodent Phyllotisxanthopygus (Waterhouse, 1837)
      (Rodentia, Cricetidae, Sigmodontinae).
AB  - Phyllotisxanthopygus (Waterhouse, 1837) is an Andean rodent endemic to South
      America. Despite its wide geographical distribution in Argentina, few individuals
      have been studied on the cytogenetic level and only through conventional
      staining. In this work, chromosome characterization of Argentine samples of this
      species was performed using solid staining, C-banding and base-specific
      fluorochromes. Twenty two specimens were analyzed, collected in the provinces of
      Jujuy, Catamarca, and the north and south of Mendoza. All studied specimens
      showed 2n=38, having mostly the bi-armed autosomes, metacentric or
      submetacentric. Fundamental Number varied between 70 and 72. These changes were
      due to the presence of chromosome heteromorphisms in individuals from southern
      Mendoza and Jujuy. C-banding revealed pericentromeric blocks of constitutive
      heterochromatin in most chromosomes. Acrocentric chromosomes involved in
      heteromorphisms showed high variation in the amount of heterochromatin within and
      among populations. Additionally, banding with fluorochromes (DAPI and chromomycin
      A3) revealed homologous localization of AT and GC rich regions among chromosomes
      of the different populations analyzed. Comparisons among heteromorphic pairs
      suggested, however, that the variation might be the result of complex chromosome
      rearrangements, involving possibly amplifications and/or deletions of
      heterochromatic segments. These results are in accordance with molecular studies
      that indicate genetic variability within and among the populations of this taxon.

PMID- 25610550
TI  - Transcatheter versus surgical closure of atrial septum defect: a debate from a
      developing country.
AB  - INTRODUCTION: This study compares the effectiveness and cost of trans-catheter
      verses surgical closure of secundum atrial septum defect (ASD). ASD accounts for
      10% of congenital cardiac defects. Trans-catheter closure of secundum ASD is
      increasingly used as the primary intervention. Surgical repair is advised in a
      proportion of secundum type defects which are unsuitable for device closure.
      METHODS: We reviewed the clinical course of 176 patients who underwent closure of
      isolated secundum ASD. The patients were assigned to either the device or
      surgical group depending upon the treatment they received. Successful closure was
      assessed immediately after the procedure. The following outcomes were studied:
      mortality, morbidity, hospital stay, and costs. RESULTS: Ninety five patients
      were in the surgical group and 81 patients were in the group undergoing device
      closure. The median age was 14.0 years (range 1.1-61.0) for surgical group and
      24.0 years (range 0.5-68.0) for the device group. The mortality in both groups
      was 0. The procedure success rate was 100% for the surgical group and 96.3% for
      the device group. The complication rate was 13.7% for surgical group and 7.4% for
      the device group. The mean length of hospital stay was 5.0 +/- 2.7 days for
      surgical group and 3.0 +/- 0.4 days for device group. The procedure cost for
      surgery was found to be 12.3% lower than that of trans-catheter closure.
      CONCLUSION: Successful closure is achieved by both methods. Trans-catheter
      closure results in lower rate of complication and hospital stay but the cost of
      the procedure tends to be higher than surgery.

PMID- 25610551
TI  - Predictors of prolonged mechanical ventilation after open heart surgery.
AB  - INTRODUCTION: Due to the importance of prolonged mechanical ventilation (PMV) as
      a postoperative complication, predicting "high-risk" patients by identifying
      predisposing risk factors is of important issue. The present study was aimed to
      identify perioperative variables associated with PMV in patients undergoing open
      heart surgery. METHODS: A total of 743 consecutive patients, American Society of
      Anesthesiologists (ASA) physical status class III, who were scheduled to undergo
      open heart surgery using cardiopulmonary bypass were included in this
      observational study. Perioperative variables were compared between the patients
      with and without PMV, as defined by an extubation time of >48 h. RESULTS: PMV
      occurred in 45 (6.1%) patients. On univariate analysis, pre-operative variables;
      including gender, history of chronic obstructive pulmonary disease (COPD);
      chronic kidney disease and endocarditis, intra-operative variables; including
      type of surgery, operation time, pump time, transfusion in operating room and
      postoperative variables; including bleeding and inotrope-dependency were
      significantly different between patients with and without PMV (all P<0.001,
      except for COPD and transfusion in operating room; P=0.004 and P=0.017,
      respectively). CONCLUSION: Our findings reinforce that risk stratification for
      predicting delayed extubation should be an important aspect of preoperative
      clinical evaluation in all anesthesiology settings.

PMID- 25610552
TI  - Effect of peripheral edema on oscillometric blood pressure measurement.
AB  - INTRODUCTION: Blood pressure (BP) measurement is essential for epidemiological
      studies and clinical decisions. It seems that tissue characteristics can affect
      BP results and we try to find edema effect on BP results taken by different
      methods. METHODS: BP of 55 children before open heart surgery were measured and
      compared according to three methods: Arterial as standard and reference,
      oscillometric and auscultatory methods. Peripheral edema as a tissue
      characteristic was defined in higher than +2 as marked edema and in equal or
      lower than +2 as no edema. STATISTICAL ANALYSES: data was expressed as Mean and
      95% of confidence interval (CI 95%). Comparison of two groups was performed by T
      independent test and of more than two groups by ANOVA test. Mann-Whitney U and
      paired T-test were used for serially comparisons of changes. P less than 0.05 was
      considered significant. RESULTS: Fifty five children aged 29.4+/-3.9 months were
      divided into two groups: 10 children with peripheral edema beyond +2 and 45 cases
      without edema. Oscillometric method overestimated systolic BP and the Mean (CI
      95%) difference of oscillometric to arterial was 4.8 (8/-1, P=0.02) in edematous
      and 4.2 (7/1, p=0.004) in non edematous. Oscillometric method underestimated
      diastolic BP as -9 (-1.8/-16.5, P=0.03) in edematous group and 2.6 (-0.7/+5, P=
      0.2) in non edematous compared to arterial method. CONCLUSION: Oscillometric
      device standards cannot cover all specific clinical conditions. It underestimates
      diastolic BP significantly in edematous children, which was 9.2 mmHg in average
      beyond the acceptable standards.

PMID- 25610553
TI  - Effect of gastroesophageal reflux disease on disease severity and characteristics
      of lung functional changes in patients with asthma.
AB  - INTRODUCTION: Almost one third of patients with asthma have symptomatic evidence
      for coexisting gastroesophageal reflux disease (GERD), which is thought to be
      aggravating factor in asthma at least in some cases. We investigated the impact
      of coexisting GERD on asthma severity and parameters of lung function. METHODS:
      Ninety two asthma patients diagnosed according to ATS criteria were studied.
      After full history and physical examination, asthma severity was measured in each
      patient using asthma control test (ACT). GERD symptoms was verified in each
      patient. Impulse oscillometry (IOS) and lung volume studies (using body
      plethysmography and IOS) were performed. The difference between total airway
      resistance (TAWR) indicated by resistance at 5 Hz and central airway resistance
      (CAWR) as indicated by resistance at 20 Hz in oscillometry was calculated and
      considered as representative of resistance at peripheral airways (PAWR). The
      relationship between the presences of GERD symptoms, ACT score and parameters of
      lung function were analyzed. RESULTS: PAWR and TAWR were both significantly
      higher in asthmatic patients with GERD symptoms than patients without GERD
      symptoms (256.64+/-161.21 versus 191.68+/-98.64; P=0.02, and 102.73+/-122.39
      versus 56.76+/-71.43; P=0.01, respectively). However, no significant difference
      was noted in mean values of ACT, FEV1 (forced expiratory volume in 1 sec), FVC
      (forced vital capacity), PEF (peak expiratory flow), and CAWR in these two
      groups. CONCLUSION: These findings suggest that the severity of asthma as
      measured by ACT score is not different in patients with and without GERD
      symptoms. However, total and peripheral airway resistance measured by IOS is
      significantly higher in asthmatic patients with GERD symptoms.

PMID- 25610554
TI  - Immediate Postoperative Complications in Patients Undergoing CABG; Investigating
      the Role of Prior Coronary Stenting.
AB  - INTRODUCTION: Approximately 15 to 30% of patients undergoing percutaneous
      coronary intervention (PCI) will require repeated revascularization. There is an
      ongoing debate concerning the impact of prior PCI on subsequent coronary artery
      bypass graft (CABG) surgery. This study sought to compare immediate post-CABG
      complications between patients with and without previous coronary stenting.
      METHODS: A total of 556 CABG candidates including 73 patients with previous
      coronary stenting and 483 patients without prior stenting were enrolled in this
      retrospective-prospective study. Demographic information, cardiac markers (CK-MB,
      Troponin T), and postoperative data including inotrope administration, intra
      aortic balloon pump (IABP) use, bleeding, pathological electrocardiography (ECG)
      changes, and overall complications were compared between the two groups. RESULTS:
      The mean age of the patients in stented group was significantly higher than that
      in unstented group (63.49+/-7.71 vs. 61.37+/-9.80 years, p=0.05). The mean serum
      level of Troponin T 12 h postoperation was significantly higher in the same group
      (323.26+/-33.16 vs. 243.30+/-11.52 ng/dL; p=0.03). Comparing the stented and
      unstented groups, the rates of inotrope use (17.8% vs. 7.2%; p=0.003),
      significant bleeding (15.1% vs. 4.3%; p=0.001), and overall complications (32.9%
      vs. 11.6%; odds ratio: 3.74 with 95% confidence interval of 2.13-6.55, p<0.001)
      were significantly higher in the former group. The association between overall
      complications and prior stenting was independent (odd ratio: 3.06). No
      significant connections were found between postoperative complications and stent
      number or type. CONCLUSION: A positive history of previous coronary stenting
      significantly increases the risk of immediate post-CABG complications.

PMID- 25610555
TI  - Epicardial and pericardial fat volume correlate with the severity of coronary
      artery stenosis.
AB  - INTRODUCTION: Epicardial fat volume (EFV) has been reported to correlate with the
      severity of coronary artery disease (CAD). Pericardial fat volume (PFV) has
      recently been reported to be strongly associated with CAD severity and presence.
      We aimed to investigate the relationship between EFV and PFV with severity of
      coronary artery stenosis in patients undergoing 64-slice multi-slice computed
      tomography (MSCT). METHODS: One hundred and fifty one patients undergoing MSCT
      for suspected CAD were enrolled. Non-enhanced images were acquired to assess
      calcium score. Contrast enhanced images were used to quantify EFV, PFV and
      severity of luminal stenosis. RESULTS: Coronary artery stenosis was mild in 25
      cases (16.6%), moderate in 58 cases (38.4%) and severe in 68 cases (45%). With
      increase in severity of coronary artery stenosis, there was significant increase
      in PFV, EFV as well as epicardial fat thickness in right ventricle free wall in
      basal view and epicardial fat thickness in left ventricle posterior wall in mid
      and apical view. There was significant linear correlation between PFV with
      coronary calcification score (r=0.18, P=0.02), between coronary artery stenosis
      severity and PFV (r=0.75, P<0.001), EFV (r=0.79, P<0.001), apical epicardial fat
      thickness in right ventricle free wall (r=0.29, P<0.001), Mid (r=0.28, P<0.001)
      and basal (r=0.23, P=0.004) epicardial fat thickness in left ventricle posterior
      wall. CONCLUSION: PFV, EFV and regional epicardial thickness are correlated with
      severity of CAD and could be used as a reliable marker in predicting CAD
      severity.

PMID- 25610556
TI  - Determinants of Atrial Electromechanical Delay in Patients with Functional Mitral
      Regurgitation and Non-ischemic Dilated Cardiomyopathy.
AB  - INTRODUCTION: Atrial conduction time has important hemodynamic effects on
      ventricular filling and is accepted as a predictor of atrial fibrillation. In
      this study we assessed atrial conduction time in patients with non ischemic
      dilated cardiomyopathy (NIDCMP) and functional mitral regurgitation (MR) and
      aimed to determine factors predicting atrial conduction time prolongation.
      METHODS: Sixty five patients with non ischemic dilated cardiomyopathy who have
      moderate to severe MR and 60 control subjects were included in the study. In
      addition to conventional echocardiographic measures used to asses left ventricle
      and MR, atrial electromechanical coupling (time interval from the onset of P wave
      on surface electrocardiogram [ECG] to the beginning of A wave interval with
      tissue Doppler echocardiography [PA]), intra- and interatrial electromechanical
      delay (intra and inter AEMD) were measured. RESULTS: The correlations between
      inter AEMD and left atrial (LA) size, MR volume, isovolumetric relaxation time
      (IVRT), deceleration time (DT), systolic pulmonary artery pressure (PAPs), E/A
      ratio and E/e' were very poor. Similarly, intra AEMD was not correlated to LA
      size , MR volume, IVRT, DT, PAPs, E/A ratio and E/e'. However, both inter AEMD
      and intra AEMD had good correlation with left ventricular mass index, tenting
      area (TA), tenting distance (TD), coaptation septal distance (CSD), sphericity
      index (SI). CONCLUSION: Prolongation of inter and intra AEMDs were found to be
      well correlated with parameters reflecting left ventricular and mitral annular
      remodeling.

PMID- 25610557
TI  - Patient's Radiation Exposure in Coronary Angiography and Angioplasty: The Impact
      of Different Projections.
AB  - INTRODUCTION: We aimed to determine angiography projections with lower Dose Area
      Product (DAP) rate by measuring the mean DAP and fluoroscopy times in coronary
      angiography (CAG) and percutaneous coronary intervention (PCI) and calculating
      DAP rate in different projections. METHODS: DAP and fluoroscopy times were
      measured in all employed projections in real-time in 75 patients who underwent
      CAG or PCI by a single cardiologist in Madani Cardiovascular University Hospital
      (45 in CAG group and 30 in PCI group). DAP rate was calculated in both groups and
      in all projections. The projections with highest and lowest DAP rate were
      determined. RESULTS: Mean DAP was 436.73+/-315.85 dGy*cm(2) in CAG group and
      643.26+/-359.58 dGy*cm(2) in PCI group. The projection 40 degrees  LAO/0 degrees 
      had the highest DAP rate in CAG group (28.98 dGy*cm(2)/ sec) and it was highest
      in 20 degrees  RAO/30 degrees  CR in PCI group (29.83 dGy*cm(2)/sec). The latter
      projection was also the most employed projection in PCI group. CONCLUSION: The
      amount of radiation dose in this study is in consistent with the previous
      reports. Specific angiographic projections expose patients to significantly
      higher radiation and they should be avoided and replaced by less irradiating
      projections whenever possible.

PMID- 25610558
TI  - A study on the mortality and complication rates following percutaneously
      adjustable pulmonary artery banding.
AB  - INTRODUCTION: Pulmonary artery (PA) banding is a procedure associated with high
      morbidity and mortality rates. It however can effectively palliate several forms
      of congenital heart lesions with increased pulmonary flow. Occasionally, to
      obtain an optimal degree of banding following operation, readjustment of the band
      is inevitable. We describe the technique of adjustable PA banding to prevent this
      problem. METHODS: From June 2007 to 2008, 21 patients with congenital cardiac
      abnormalities including Single ventricle (1), transposition of great arteries
      (TGA) (4) and ventricular septal defect (VSD) (16) were operated via
      percutaneously adjustable PA banding in Madani Hospital (Tabriz, Iran). RESULTS:
      The mean age and the mean weight of the patients were 12+/-.8 months and 61+/-.7
      kg respectively. Seventeen (81%) patients survived the operation. Cause of death
      was heart failure in 2 (9.5%) patients, and arrhythmia in 2 (9.5%) patients.
      Later, patients were followed up for 6 months. Satisfactory band gradient was
      achieved between 48 and 240 hours. Mean PA gradient before and 1 and 6 months
      after adjusting was (55.3+/-7.1 mmHg), (54.7+/-5.1 mmHg), and (53.2+/-5.4 mmHg)
      respectively. In the follow up period, there were 2 deaths, one caused by
      aspiration pneumonia and one caused by poor mixing. Postoperative complications
      were observed in 28.5% of the cases including cardiac (10%), pulmonary
      (pneumothorax, pneumonia) (10%) and infectious complications (9%). CONCLUSION:
      The technique of percutaneously adjustable PA banding is simple and inexpensive
      and allows easy band adjustments without the need for multiple reoperations.
      Moreover, our assessment reveals that created gradient is constant and did not
      decrease with time.

PMID- 25610559
TI  - Effects of intravenous indomethacin on reduction of symptomatic patent ductus
      arteriosus cases and decreasing the need for prolonged mechanical ventilation.
AB  - INTRODUCTION: We decided to investigate the effects of injecting Indomethacin on
      reducing complications of Patent Ductus Arteriosus (PDA) and the need for
      prolonged mechanical ventilation. METHODS: During this randomized clinical trial,
      70 premature infants with matched gestational age and birth weight were divided
      into case and control groups. In the study group, intravenous indomethacin
      started from the first 2-12 hours of birth. All patients were followed by
      echocardiography at the fourth day and skull ultrasound in the second week.
      RESULTS: Symptomatic PDA rate was significantly higher in the control group
      (25.7% vs. 0%; P<=0.001). Incidence of grade 1-3 intraventricular hemorrhage was
      higher in the control group and the ratio of needed time for respiratory support
      in the control group to the case group was approximately 2.1. CONCLUSION:
      Intravenous Indomethacin reduced the number of PDA cases and incidence of grade 2
      and 3 intraventricular hemorrhage, without any short term side effects.

PMID- 25610561
TI  - The Importance of Total Neutrophil Count and Neutrophil/Lymphocyte Ratio in ST
      Elevation Myocardial Infarction.

PMID- 25610560
TI  - Calcified amorphous tumor of the heart with purple digit.
AB  - A calcified amorphous tumor (CAT) of the right atrium (RA) is an exceedingly rare
      non-neoplastic cardiac mass. It was initially described in 1997 and only a
      handful of cases has been published so far. We present a case of tumor in 77-year
      old male, in the RA that attached to the rim of the fossa ovalis, with classic
      pathological and clinical findings. Under cardiopulmonary bypass (CPB) and
      bicaval and aortic cannulation and cardioplegic arrest, right atrial mass, was
      resected and septal defect was repaired with a fresh pericardial patch.
      Pathological exam of the mass revealed CAT. The patient had an uneventful
      hospitalization and his blue discoloration of finger recovered normally. 

PMID- 25610562
TI  - The roles of veterinarians in meeting the challenges of health and welfare of
      livestock and global food security.

PMID- 25610563
TI  - Blastema from rabbit ear contains progenitor cells comparable to marrow derived
      mesenchymal stem cells.
AB  - Rabbits have the capacity to regenerate holes in their ears by forming a
      blastema, a tissue that is made up of a group of undifferentiated cells. The
      purpose of the present study was to isolate and characterize blastema progenitor
      cells and compare them with marrow mesenchymal stem cells (MSCs). Five New
      Zealand white male rabbits were used in the present study. A 2-mm hole was
      created in the animal ears. After 4 days, the blastema ring formed in the
      periphery of the hole was removed and cultivated. The cells were expanded through
      several subcultures and compared with the MSCs derived from the marrow of same
      animal in terms of in vitro differentiation capacity, growth kinetics and culture
      requirements for optimal proliferation. The primary cultures from both cells
      tended to be heterogeneous. Fibroblastic cells became progressively dominant with
      advancing passages. Similar to MSCs blastema passaged-3 cells succeeded to
      differentiate into bone, cartilage and adipose cell lineages. Even lineage
      specific genes tended to express in higher level in blastema cells compared to
      MSCs (p < 0.05). Moreover blastema cells appeared more proliferative; producing
      more colonies (p < 0.05). While blastema cells showed extensive proliferation in
      15% fetal bovine serum (FBS), MSCs displayed higher expansion rate at 10% FBS. In
      conclusion, blastema from rabbit ear contains a population of fibroblastic cells
      much similar in characteristic to bone marrow mesenchymal stem cells. However,
      the two cells were different in the level of lineage-specific gene expression,
      the growth curve characteristics and the culture requirements. 

PMID- 25610564
TI  - Antibacterial, antioxidant and optical properties of edible starch-chitosan
      composite film containing Thymus kotschyanus essential oil.
AB  - Thyme Essential oils (EO) with antimicrobial and antioxidant properties are
      widely used in pharmaceutical, cosmetic, and perfume industry. It is also used
      for flavoring and preservation of several foods. Nowadays, packaging research is
      receiving a considerable attention due to the development of eco-friendly
      materials made from natural polymers such as starch and chitosan. In this study
      Thymus kotschyanus EO concentrations ranging from 0 to 2.0%, incorporated in
      starch-chitosan composite (S-CH) film were used. Antimicrobial and antioxidant
      properties significantly increased with the incorporation of EO (p < 0.05).
      Incorporating EO, increased total color differences (DE), yellowness index (YI)
      and whiteness index (WI) which were significantly higher than control and its
      transparency was reduced. Our results pointed out that the incorporation of
      Thymus kotschyanus EO as a natural antibacterial agent has potential for using
      the developed film as an active packaging. 

PMID- 25610565
TI  - Growth and reproductive performance by different feed types in fresh water
      angelfish (Pterophyllum scalare Schultze, 1823).
AB  - It is well established that reproduction is sensitive to the state of energy
      reserves, and that there is a balance between energy homeostasis and fertility.
      In this view, this study examined the effects of different diets on growth and
      reproductive performance of fresh water angelfish. Twenty four pairs of angelfish
      (weighing 3.58 +/- 0.24 g) were fed with four types of diets including live earth
      worm (LEW), dried Tubifex (DT), dried Gammarus (DG) and prepared granulated feed
      (PGF), twice a day for 90 days. Reproductive parameters were measured between
      days 60 and 90. The significant increase in the gonadosomatic index (GSI),
      fecundity and hatchability brought about by the LEW were demonstrated by the
      higher number of spawned eggs and hatched larvae. The best growth observed
      significantly in PGF, and length of larvae was enhanced in this group,
      consequently. The numbers of dead and deformed fry were lower in the fish fed
      with PGF and LEW, but there was no significant difference among experimental
      groups. This study showed that breeders benefit from inclusion of prepared
      granulated feed and living earth worm during their growth and reproductive
      stages, and simultaneous using of them for achieving better results is suggested.

PMID- 25610566
TI  - Investigation of antibacterial, acid and bile tolerance properties of
      lactobacilli isolated from Koozeh cheese.
AB  - Lactobacillus strains are a major part of the probiotics, microflora of the
      intestine and of fermented dairy products, and are found in a variety of
      environments. The aim of this study was to find out the ability of bile and acid
      tolerance and antibacterial properties of the twenty eight isolates of three
      group lactobacilli namely Lactobacillus plantarum, Lactobacillus casei and
      Lactobacillus delbruki. For this purpose Twenty eight different Lactobacillus
      strains that isolated from Koozeh cheese as a traditional cheese were screened.
      The acid tolerance test was studied under pH 2.0 and 3.0 with 7.5 as control. The
      cell count for the acid tolerance test was obtained at an interval of 0, 1, 2 and
      3 hours respectively and was pour plated on Man, Rogosa, and Sharpe (MRS) agar to
      be incubated at 37  degrees C for 24 hours. All cells were selected for bile
      tolerance test in MRS broth containing bile concentrations of 0% as control and
      0.3% as test. Then cell counts were enumerated after 24 hours of incubation on
      MRS agar. Results showed twenty seven isolates did not have ability to tolerate
      acid and bile salts and antimicrobial activity against four indicator bacteria
      included Eshirichia coli, Listeria monocytogenesis, bacillus cereus, Salmonella
      entritidis. Only one Isolate namely Lactobacillus casei could tolerate acid and
      bile salt and had antibacterial activity against of L. monocytogenesis. Therefore
      we can consider this strain as a native probiotic but extra examinations was
      required. 

PMID- 25610567
TI  - Melatonin improves spatial navigation memory in male diabetic rats.
AB  - The aim of the present study was to evaluate the effect of melatonin as an
      antioxidant on spatial navigation memory in male diabetic rats. Thirty-two male
      white Wistar rats weighing 200 +/- 20 g were divided into four groups, randomly:
      control, melatonin, diabetic and melatonin-treated diabetic. Experimental
      diabetes was induced by intraperitoneal injection of 50 mg kg(-1) streptozotocin.
      Melatonin was injected (10 mg kg(-1) day(-1), ip) for 2 weeks after 21 days of
      diabetes induction. At the end of administration period, the spatial navigation
      memory of rats was evaluated by cross-arm maze. In this study lipid peroxidation
      levels, glutathione-peroxidase and catalase activities were measured in
      hippocampus. Diabetes caused to significant decrease in alternation percent in
      the cross-arm maze, as a spatial memory index, compared to the control group (p <
      0.05), whereas administration of melatonin prevented the spatial memory deficit
      in diabetic rats. Also melatonin injection significantly increased the spatial
      memory in intact animals compared to the control group (p < 0.05). Assessment of
      hippocampus homogenates indicated an increase in lipid peroxidation levels and a
      decrease in GSH-Px and CAT activities in the diabetic group compared to the
      control animals, while melatonin administration ameliorated these indices in
      diabetic rats. In conclusion, diabetes induction leads to debilitation of spatial
      navigation memory in rats, and the melatonin treatment improves the memory
      presumably through the reduction of oxidative stress in hippocampus of diabetic
      rats. 

PMID- 25610568
TI  - Physicochemical and hygienic effects of Lactobacillus acidophilus in Iranian
      white cheese.
AB  - Increasing incidence of food-borne disease along with its social and economic
      consequences have led to conducting extensive research in order to produce safer
      food and develop new antimicrobial agents; among them, extensive use of
      probiotics and bacteriocins as biological additives is of significant importance.
      The aim of the present study was to evaluate the interactions (growth behavior
      and survival) of Listeria monocytogenes and Lactobacillus acidophilus in various
      stages of production, ripening and storage of Iranian white cheese. Changes in pH
      values at different stages of cheese ripening, along with changes in organoleptic
      properties of cheese were also assessed. Compared to other treatments, in the
      treatment of cheese with probiotic agent without starter, the most significant
      decrease in Listeria monocytogenes count at the end of ripening stage was
      observed (3.16 Log per gram cheese compared with the control group) (p < 0.05).
      Survival of probiotic bacteria in control samples of cheese were significantly
      higher when compared to cheese sample contaminated with Listeria (p < 0.05).
      White probiotic cheese with starter had the highest of sensory acceptability (p <
      0.05). Listeria Monocytogenes count decreased during ripening period of probiotic
      white cheese but the bacteria survived in probiotic white cheese. Lactobacillus
      acidophilus count decreased during ripening period of white cheese but it did not
      lower to less than 10(6) CFU per g at the end of ripening and storage periods. 

PMID- 25610569
TI  - Copper and zinc concentrations in the uterine fluid and blood serum during the
      bovine estrous cycle.
AB  - To investigate uterine and serum copper (Cu) and zinc (Zn) concentrations
      variation during the bovine estrus cycle , 232 blood and genital tract samples
      were collected from the abattoir in Urmia. The phase of the estrous cycle was
      determined by the examination of the ovaries and the uterine tonicity. Of the 46
      samples selected for use in the study, 13 were pro-estrus, 10 estrus, 8
      metestrus, and 15 diestrus. The uterus was incised and uterine fluid was
      collected by gentle scraping of the uterine mucosa with a curette. The total mean
      (+/- SEM) Cu concentrations in serum and uterine fluid samples, determined by
      spectrophotometry, were 66.1+/- 6.5 and 171.3 +/- 33.2ug dL(-1) respectively,
      which were significantly different, while total mean serum and uterine fluid Zn
      concentrations were 91.9 +/- 5.4 and 291.6 +/- 23.4 ug dL(-1), which also showed
      a significant difference. The mean serum Cu values in different phases of the
      estrous cycle were not significantly different, while uterine fluid Cu content in
      pro-estrus and diestrus were significantly higher than those in estrus and
      metestrus, and were also significantly higher than those of the serum samples.
      The mean Zn value of serum samples at different stages of the cycle was not
      significantly different. The mean Zn value of the uterine fluid samples was also
      not significantly different in different stages, but in pro-estrus, metestrus,
      and in diestrus they were highly significantly different from those of the serum.
      These results showed that Cu concentrations in the uterine fluid vary at
      different stages of the cycle and are higher than those in the blood serum, but,
      the uterine Zn content does not vary during the estrous cycle and is much higher
      than those in the serum, that seems to be due to the secretory action of the
      uterine mucosa. 

PMID- 25610570
TI  - Histopathological study of the mite biting (Dermanyssus gallinae) in poultry
      skin.
AB  - The red mite of poultry, Dremanyssus gallinae, is the most important
      hematophagous ectoparasite of poultry. In this study, pathologic changes of its
      biting on the poultry skin have been investigated. Thirty-two (Control = 16 and
      Treatment = 16) four weeks old Ross broilers (308) were infested with the mite on
      skin of hock joins. Samples were collected after 1, 24, 72 hours and 10 days. The
      skin samples were fixed in 10% buffered formalin and histological sections were
      prepared using routine Hematoxylin & Eosin staining method. Results showed that
      in all cases, except within first hour of infestation, lymphocytic infiltration
      was always a constant pathologic feature. Necrosis of feather's follicles was a
      prominent pathologic feature ensued due to vascular disturbances and resulted in
      loss of feather. Hyperkeratosis, parakeratosis and acanthosis were observed after
      72 hours. These findings reveal that mite biting induces local epidermal
      hyperplasia. 

PMID- 25610571
TI  - Serum concentrations of haptoglobin and serum amyloid A in water buffaloes
      (Bubalus bubalis) with abomasal ulcer.
AB  - To evaluate the serum concentrations of haptoglobin (Hp) and serum amyloid A
      (SAA) in water buffaloes with abomasal ulcers, the abomasums of 100 randomly
      selected water buffaloes were examined after slaughter. Type I abomasal ulcers
      were found in 56 out of 100 buffaloes. Serum concentrations of Hp and SAA were
      measured. There was no significant difference between affected and non-affected
      buffaloes in the serum concentrations of Hp and SAA. The serum concentrations of
      Hp and SAA had no significant correlation with age and the serum SAA revealed no
      significant correlation with the number of abomasal ulcers. A significant
      correlation was found between the serum Hp and the number of abomasal ulcers (r
      =0.29, p = 0.04). There was no significant difference in the serum concentrations
      of Hp and SAA between buffaloes with different ulcer locations in the abomasums.
      Although more work on a larger number of animals is required in this area, it
      seems that the measurement of the serum Hp can be used to predict the abundance
      of type I abomasal ulcers. 

PMID- 25610572
TI  - Efficiency of utilization of dietary energy for milk production in lactating
      crossbred cattle (Bos Indicus).
AB  - The present study was conducted on efficiency of utilization of dietary energy
      for milk production in lactating crossbred cattle. 18 lactating crossbred cattle
      of early to mid-lactation, approximate body weight (375.39+/-23.43 kg), milk
      yield, parity and stage of lactation were divided into three groups of six
      animals each and were fed 0, 50 and 100% diammonium phosphate (DAP) in the
      mineral mixture of concentrates for 120 days. The chaffed mixed roughage (berseem
      + wheat straw) and concentrate mixture was fed to supply about nearly 18:82
      concentrate to roughage ratio on dry matter basis. Tap water was available to the
      animals twice daily. A metabolism trial of seven days was conducted at the end of
      experiment to study digestibility of organic nutrients and balances of energy.
      DAP did not affect the nutrient intake, body weight changes, digestibility of Dry
      matter (DM), Crude protein (CP), Ether extract (EE), Crude fiber (CF), Nitrogen
      free extract (NFE) and daily milk yield. It was concluded that the at 46.07 Mcal
      Gross energy intake level the losses in feces, urine, methane and heat production
      was 45.82%, 5.40%, 4.31% and 33.01%, respectively, and net energy retention for
      milk production was 11.43%. The gross efficiency of conversion of metabolic
      energy ME for milk production was 35.69% and the net efficiency of conversion of
      ME for milk production was 39.56%. 

PMID- 25610573
TI  - Ear necrosis syndrome in weaning pigs associated with PCV2 infection: A case
      report.
AB  - Porcine necrotic ear syndrome (PNES) in pigs has been reported as an increasing
      health problem in many countries with intensive pig farming. The etiology of this
      disease is complex and the presumed triggering factors can be divided into
      infectious and non-infectious agents. The present report describes a case of
      Porcine Circovirus type 2 (PCV2), infection associated with lesions of PNES at
      the weaning stage of a farrow-to-finish pig farm. Approximately 35% of weaners (1
      3 weeks after weaning) presented clinical symptoms similar to Post-weaning
      Multisystemic Wasting Syndrome (PMWS). About 2-3 weeks after weaning the first
      lesions of PNES occurred in approximately 20% of pigs, resulting in a significant
      health problem characterized by poor growth or severe wasting and finally
      mortality up to 15% in some batches. Moreover, approximately 5% of survived
      weaners, during growing / finishing stage, presented poor growth and secondary co
      infections that lead to death. The present study based on the clinical signs,
      serological and pathological examinations, indicates that weaners suffered by sub
      acute PCV2 infection resulting in PMWS associated with PNES. The lesions of PNES
      were initially observed at the same period (4-8 weeks of age) with the higher
      seroprevalence of PCV2 infection. Metaphylaxis of this case included
      intramuscular injection of florfenicol for the treatment and control of skin
      lesions and respiratory signs. Moreover, piglets were vaccinated against PCV2. In
      conclusion, sub-acute PCV2 infection could be included in triggering factors PNES
      in weaners. The mass vaccination against PCV2 of infected piglets might be
      effective in reduction of clinical signs and losses of PNES in cases of PCV2
      infection associated with PNES. 

PMID- 25610574
TI  - A typical case of hydrallantois accompanied by fetal monstrosity in a local ewe
      of Kashmir.
AB  - A full termed local ewe with the history of continuous straining with labored
      breathing for last 24 hours was presented. The animal was disinclined to move
      with tense and round abdomen which developed rapidly during last two weeks.
      Caesarean section revealed hydrallantois accompanied by multiple fetal congenital
      abnormalities. The ewe was under observation for four weeks. Metritis developed
      12 days post-operation and was treated successfully. The ewe was found active on
      25 days post-surgery with gain of extra 3 kg bodyweight. 

PMID- 25610575
TI  - Luteal activity of Abadeh ecotype does in summer and winter and the effect of
      kisspeptin-10 on luteinizing hormone secretion in the anestrus does.
AB  - The aims of the present study were to evaluate luteal activity in Abadeh ecotype
      goat during summer and winter and also the effect of a single dose kisspeptin-10
      injection on the secretion of luteinizing hormone (LH) in female anestrous goats.
      In the first study, progesterone (P4) concentration in 10 goats in summer (n = 6)
      and winter (n = 4) were measured every other day. Moreover, in summer group, a
      male teaser goat was left in the herd on days of sampling for one hour. Goats
      with P4 concentration >=1 ng mL(-1), at least two consecutive measurements, were
      considered with luteal activity. In the second study, the anestrous phase was
      confirmed by P4 measurement 20 and 10 days before the kisspeptin injection in
      five female Abadeh ecotype goats (4 to 5 years old). The goats were given a
      single IV injection of saline (2 mL) as control group and the same goats (1 hr
      after the last blood sampling) were given kisspeptin (1 MUg kg(-1)) as treatment
      group. The blood samples were collected at -60, -40, -20 and 0 min (before
      injection), and 10, 20, 30, 40, 50, 60, 80, 100, 120 and 140 min after the
      injection and LH concentration were measured. A single IV injection of 1 ug kg(
      1) of kisspeptin-10 did not stimulate the release of LH in female anestrous
      goats. In summer, in the presence of teaser goat, luteal activity was seen in all
      goats. In the absence of male goat in winter, some goats showed luteal activity
      and others showed anestrus. 

PMID- 25610576
TI  - Molecular and clinical study on prevalence of feline herpesvirus type 1 and
      calicivirus in correlation with feline leukemia and immunodeficiency viruses.
AB  - Upper respiratory tract diseases (URTD) are common clinical problem in cats
      worldwide. Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the
      main primary pathogens. Feline immunodeficiency virus (FIV) and Feline leukemia
      virus (FeLV) are also among the most common infectious diseases of cats which
      suppress the immunity. Oropharyngeal and conjunctival swabs and blood samples
      were taken from 16 cats with clinical signs of URTD and 26 clinically healthy
      cats. PCR and RT-PCR were used to detect FHV/FIV or FCV/FeLV infections,
      respectively. Feline calicivirus was detected in all cats with URTD and 87.00%
      and 93.00% of them were positive for FIV and FeLV, respectively. Feline
      herpesvirus rate of infection was 43.00% in sick cats. In clinically normal cats,
      prevalence rates of FCV and FHV were about 50.00%, but FIV and FeLV rates (42.00%
      and 65.00% respectively) were higher compared to other studies. Stomatitis was
      observed in 50.00% of cats with URTD. The main causative agent of corneal ulcers
      is FHV-1, but in 50.00% of cats with corneal ulcers, FCV was detected alone. It
      seems new variants of Caliciviruses are the main causative agents to attack
      uncommon tissues like cornea, although retroviral infections may be in the
      background of these various signs. The high retroviral prevalence may be due to
      existence of large population of stray cats. This is the first molecular study of
      FeLV and FCV in Iran and seems that FCV and FHV prevalence rates in FIV or FeLV
      infected cats is more than other non-infected ones. 

PMID- 25610577
TI  - Protective effects of pomegranate seed oil on ovariectomized rats as a model of
      postmenopausal osteoporosis: A multi-detector computed tomography evaluation.
AB  - The pomegranate seed oil (PSO), containing 17-alpha-estradiol, is one of the
      newly found phytosterols with synergistic health effects on estrogen related
      physiological conditions. Herein, PSO was assessed for its potential improving
      effects on bone characteristics in a rat model of menopausal syndrome. Three
      month old non-pregnant female Wistar rats (n = 30) were either sham-operated
      (SHAM) or ovariectomized (OVX), each divided into two further groups receiving
      0.1 mL PSO or the same volume of paraffin oil as placebo. Before the operation
      and 67 days after it, multi-detector computed tomography (MDCT) scanning was
      performed with the identical setup option for the scanner to measure the bone
      mineral density (BMD) in body of 12(th) thoracic vertebra, 1(st) to 6(th) lumbar
      vertebra and sacrum. This study revealed that bone density of 1(st), 3(rd),
      5(th), 6(th) and sacrum body were significantly different between OVX and SHAM
      groups during the study period. In conclusion, PSO during 67 days study could not
      completely prevent the osteoporotic effects caused by ovariectomy in vertebral
      column of rats. 

PMID- 25610578
TI  - Detection of tetracycline resistance genes in bacteria isolated from fish farms
      using polymerase chain reaction.
AB  - Five common tetracycline resistance genes tet(A), tet(B), tet(M), tet(O) and
      tet(S) were studied by polymerase chain reaction in 100 bacteria isolated from
      Iranian fish farms. In the antibiogram test most of the bacteria were either
      intermediately or completely resistant to tetracycline. Nine isolates out of 46
      Aeromonas spp. contained either tet(A/M/S) resistant genes as follows: tet(A) in
      A. veronii/sobria (n = 1), A. media (n = 2), A. aquariorum (n = 1), and A.
      veronii (n = 3); tet(M) in one isolate of A. sobria and tet(S) in 1 isolate of A.
      jandaei. In other bacteria, tet(A) gene was detected in Citrobacter freundi (n =
      1), Pseudomonas putida (n = 1); tet(S) was also identified in Yersinia ruckeri (n
      = 1), Arthrobacter arilaitensis (n = 1) and P. putida (n = 1). In total, 31
      isolates (31.00%) contained the tetracycline resistance genes in which 21
      bacteria (21.00%) showed the tet(S), nine bacteria (9.00%) contained the tet(A)
      and 1 bacteria (1.00%) was positive for tet(M). All of the L. garvieae isolates
      contained tet(S) in this study. The most widely distributed resistance gene was
      gene tet(A) and the least known resistance genes was tet(M) among the studied
      bacteria of the genus Aeromonas in this study. 

PMID- 25610579
TI  - Effect of different supplements on eggshell quality, some characteristics of
      gastrointestinal tract and performance of laying hens.
AB  - This study was performed to investigate the effects of antibiotic, organic acid,
      probiotic and prebiotic supplementation on performance, egg shell quality, pH
      value of gastrointestinal (GI) tract and small intestinal morphology of laying
      hens. The experiment was a completely randomized design with 160 laying hens
      strain (W-36) from 32 to 42 weeks of age, with five treatments, four replicates
      and eight hens in each replicate. The experimental treatments consisted of: 1
      basal diet, 2-basal diet + 150 g per ton antibiotic (oxytetracycline), 3-basal
      diet + 3 kg per ton mixture of organic acids supplementation, 4- basal diet + 50
      g per ton probiotic (protoxin) and 5-basal diet + 2 kg per ton prebiotic (mannan
      oligosaccharide). During the experimental period, performance characteristics
      were evaluated. At the end of experiment two birds per replicate was sacrificed
      for small intestinal morphology. The results showed that organic acid and mannan
      oligosaccharide significantly increased average egg weight. Also feed conversion
      ratio significantly improved by mannan oligosaccharide. Eggshell quality was not
      significantly affected by dietary treatments. Regarding gastrointestinal tract
      characteristics, pH value of different parts of GI tract were significantly
      affected by dietary treatments. Villi height in duodenum by probiotic and in
      ileum by mannan oligosaccharide significantly increased. Villi width in duodenum
      by antibiotic and probiotic and in ileum by mannan oligosaccharide significantly
      increased. The number of goblet cells in duodenum by addition of antibiotic and
      in ileum by mannan oligosaccharide significantly increased. It was concluded that
      the use of organic acids and mannan oligosaccharide could have positive effects
      on performance of laying hens. 

PMID- 25610580
TI  - Effect of a phytogenic feed additive on performance, ovarian morphology, serum
      lipid parameters and egg sensory quality in laying hen.
AB  - This present study was conducted to evaluate the effects of dietary inclusion of
      4, 8 and 12 g kg(-1) phytogenic feed additives mixture on performance, egg
      quality, ovary parameters, serum biochemical parameters and yolk trimethylamine
      level in laying hens. The results of experiment have shown that egg weight was
      increased by supplementation of 12 g kg(-1) feed additive whereas egg production,
      feed intake and feed conversion ratio (FCR) were not significantly affected.
      There were no significant differences in egg quality parameters by
      supplementation of phytogenic feed additive, whereas yolk trimethylamine level
      was decreased as the feed additive level increased. The sensory evaluation
      parameters did not differ significantly. No significant differences were found in
      serum cholesterol and triglyceride levels between the treatments but low- and
      high-density lipoprotein were significantly increased. Number of small follicles
      and ovary weight were significantly increased by supplementation of 12 g kg(-1)
      feed additive. Overall, dietary supplementation of polyherbal additive increased
      egg weigh, improved ovary characteristics and declined yolk trimethylamine level.

PMID- 25610581
TI  - Comparison digestibility and protozoa population of Khuzestan water buffalo and
      Holstein cow.
AB  - The major aim of this study was to compare the morphology and activity of rumen
      protozoa of Khuzestan water buffalo and Holstein cow using in vitro digestibility
      and gas production parameters of steam treated sugarcane pith. Rumen fluid
      obtained from two buffalo and cow steers fed the same diet, 30:70 concentrate:
      forage. To separate rumen protozoa, antibiotic solution and fungicides were added
      to rumen fluid. The results of present experiment indicated that the neutral
      detergent fiber (NDF; 7.8 vs. 1.69%) and acid detergent fiber (ADF; 6.24 vs.
      3.24%) digestibility of steam treated sugarcane pith by rumen protozoal
      population of Khuzestan buffalo was higher than those of cow (p < 0.05). Also,
      digestibility of dry matter, NDF and ADF by whole buffalo micro-organisms was
      more than those in cow (p < 0.05). The results indicated that the potential of
      gas production of sugarcane pith by rumen protozoa in water buffalo was more than
      that of cow (p < 0.05). Total rumen ciliate protozoa numbers in water buffalo
      were significantly higher than those of cow (3.68 * 10(5) vs. 2.18 * 10(5) mL(-1)
      of rumen content) (p < 0.05). The number of Diplodinium in buffalo was more than
      that of cow (41.27 vs. 35.7% of total rumen protozoa, respectively). Percentage
      of Entodinium, Epidinium, Ophryoscolex and Isotricha in cow was more than those
      of buffalo. Therefore, in the same diet, protozoa and total rumen micro-organisms
      of Khuzestan water buffalo have higher digestion activity compared to Holstein
      cow. 

PMID- 25610582
TI  - Calcium and magnesium content of the uterine fluid and blood serum during the
      estrous cycle and pre-pubertal phase in water buffaloes.
AB  - To investigate uterine fluid and serum calcium (Ca) and Magnesium (Mg) variations
      during the estrus cycle in water buffaloes, 71 genital tracts and blood samples
      were collected from the abattoir in Urmia. The phase of the estrous cycle was
      determined by examining ovarian structures. 18 animals were pro-estrous, 15
      estrous, 16 met-estrous and 22 diestrous. The uterine fluid was collected by
      gentle scraping of the uterine mucosa with a curette. Blood serum and uterine
      fluid samples of 71 pre-pubertal buffalo calves were also collected and treated
      in similar manners. The mean +/- SEM total serum and uterine fluid Ca in cyclic
      buffaloes were 8.68 +/- 0.28 mg dL(-1) and 8.10 +/- 0.2 mg dL(-1) vs. 6.76 +/-
      0.65 mg dL(-1) and 7.90 +/- 0.15 mg dL(-1) in pre-pubertal calves, respectively.
      Blood serum Mg was not different in cyclic and pre-pubertal animals but the
      uterine fluid Mg in cyclic cows was higher than those in pre-pubertal calves.
      Serum Ca in pro-estrus and estrus were higher than those in other stages and also
      higher than those in the uterine fluid. The lowest Mg content of serum was
      recorded in diestrus, while in the uterine fluid it was observed in estrus. In
      all stages of estrous cycle except for estrus the uterine fluid Mg content was
      significantly higher than those of the serum. These results suggested that during
      the estrous cycle in the buffalo cows, Ca was passively secreted in uterine lumen
      and mostly dependent on blood serum Ca concentrations but Mg was secreted
      independently. The values (except for serum total Mg) also increased after
      puberty. 

PMID- 25610583
TI  - Isolation and identification of excretory-secretory and somatic antigens from the
      Oestrus ovis larvae by SDS-PAGE and immunoblotting.
AB  - Oestrus ovis is an economically important parasite of small ruminants and a
      zoonotic parasite with many reports of ophthalmomyiasis in human from Iran and
      other countries. The aim of the peresent study was the isolation and
      identification of excretory-secretory (ES) and somatic (S) antigens of O. ovis
      second and third stage larvae (L2, L3) collected from Arabi sheep breeds located
      in southwest of Iran. Positive sera were prepared by marking the sheep, taking
      blood sample and direct observation of the parasite in the head. Somatic antigens
      of the larvae (SL2, SL3) were prepared by sonication. Larval excretory-secretory
      antigens (ESL2, ESL3) were prepared by incubation the larvae in RPMI-1640 RPMI
      medium. Electrophoretic protein profiles of ESL2 two, ESL3 seven, SL2 eight, SL3
      fifteen bands (from 79.0 to below 14.4 KDa) were shown. In immunoblotting with
      positive sera, four common bands in SL2 and SL3 at 58, 42.0, 29.0 and 28.0 kDa,
      one specific band in SL3 at 47.0 kDa and one band in ESL2, at 28.0 kDa, and three
      bands in ESL3 at 58.0, 42.0, 29.0 and 28.0 kDa were recognized. Among the
      profiles, the 28 kDa protein was the most common antigenic component.
      Nevertheless, the antigenic proteins 29, 58 kDa were a common protein in
      electrophoretic patterns of both S and ES proteins of L2 and L3 but, 42.0 kDa
      antigen the only one detected in immunoblot but not in S and ES protein profiles
      of the larvae. Therefore, the antigens 29.0, 42.0 and 58.0 kDa can be used for
      further studies of protective effects and serological diagnostic methods. 

PMID- 25610584
TI  - Physicochemical and antioxidative characteristics of Iranian pomegranate (Punica
      granatum L. cv. Rabbab-e-Neyriz) juice and comparison of its antioxidative
      activity with Zataria multiflora Boiss essential oil.
AB  - Pomegranate juice (PJ) and its products are directly used in foods due to their
      pleasant taste and palatability as well as preservative effects. In spite of
      useful effects of essential oils such as zataria multiflora Boiss essential oil
      (ZEO) on prolonging shelf-life of foods, their application is restricted due to
      their vigorous taste and aroma. In the present study, physicochemical
      characteristics, chemical compositions and antioxidative activities of two
      Iranian native plants, PJ (Rabbab-e-Neyriz cultivar) and ZEO were investigated.
      2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and reducing power tests
      were used for measuring antioxidant activity. The level of total phenolic of them
      were also determined. Total soluble solids content, pH value, titratable acidity
      content and total anthocyanins content of PJ were also measured. Chemical
      compositions of ZEO were determined using gas-chromatography, mass-spectrometry
      (GC-MS). The results of antioxidative tests indicated that the ZEO was
      significantly more potent (p < 0.05) than PJ. Also the phenolic content in ZEO
      (262.52 mg per g) was significantly higher (p < 0.05) than PJ (154.90 mg per
      100g). Chemical compositions analysis of ZEO indicated that its major components
      were carvacrol (59.17%), linalool (23.67%), trans-caryophyllene (3.07%) and
      carvacrol methyl ether (2.44%). In the present study, physicochemical and
      antioxidative characteristics of Rabbab-e-Neyriz PJ were determined for first
      time. It was aslo found that ZEO in comparison with PJ had higher antioxidative
      activity and total phenolic content. 

PMID- 25610585
TI  - Molecular detection of infectious bronchitis and Newcastle disease viruses in
      broiler chickens with respiratory signs using Duplex RT-PCR.
AB  - Infectious bronchitis (IB) and Newcastle disease (ND) are highly contagious and
      the most economically important diseases of the poultry affecting respiratory
      tract and causing economic losses in poultry industry throughout the world. In
      the present study, the simultaneous detection and differentiation of causative
      agents of these diseases were investigated using duplex-RT-PCR. RNA was extracted
      from vaccinal and reference strains of infectious bronchitis virus (IBV) and
      Newcastle disease virus (NDV) and then cDNA was synthesized. Using two universal
      primer sets for detection of IBV and NDV, the duplex-RT-PCR was developed. In
      order to assess the efficiency of the developed duplex RT-PCR, a number of 12
      broiler farms with the symptoms of respiratory tract infection was sampled
      (trachea, lung and kidney were sampled from affected birds suspicious for IBV and
      NDV infections). After RNA extraction from tissues and cDNA synthesis, the
      presence of IBV and NDV genome were investigated using duplex-PCR. The results
      showed that three of twelve examined broiler farms were positive for IBV and two
      farms were positive for NDV and IBV. The results revealed that the duplex-RT-PCR
      is a quick and sensitive procedure for simultaneously detecting IBV and NDV in
      birds with respiratory infections. 

PMID- 25610586
TI  - Seroprevalence of Bluetongue in sheep in Kohgiluyeh and Boyer-Ahmad province,
      Iran.
AB  - Bluetongue (BT) is a viral disease of ruminants transmitted by Culicoides biting
      midges and has the ability to spread rapidly over large distances. The disease
      occurs almost worldwide between latitudes approximately 35 S and 50 N. Among the
      numerous diseases of ruminants, BT has gained considerable importance in recent
      years as one of the best examples of the effects of climate change on disease
      spread. Sheep are major livestock species in Iran, but studies of BT have not
      gained the priority compared to other diseases. Thus, the objective of this study
      was to describe the distribution and seroprevalence of bluetongue virus (BTV)
      infections in sheep in Kohgiluyeh and Boyer-Ahmad province of Iran, and to
      identify factors associated with the exposure of these sheep to BTV infection.
      Sera from 262 apparently healthy sheep were collected during the year 2011. The
      collected sera of the animals were screened with competitive enzyme like
      immunosorbent assay (c-ELISA). Two hundred and three (77.48%) out of 262 sera
      tested were positive to BTV antibodies. Statistically significant differences
      were found in the seroprevalence BT, between sex and age of sheep (p < 0.001). No
      statistically significant differences were observed in BTV seroprevalence among
      different seasons, nor among recently aborted and normally delivered. 

PMID- 25610587
TI  - A report on the genital myiasis by Wohlfahrtia magnifica in camel herds in
      southwest of Iran.
AB  - Myiasis is a disease of vertebrate animals caused by different fly larvae.
      Wohlfahrtia magnifica is responsible for serious losses in animal husbandry in
      Eurasia. Larvae of W. magnifica parasitize several warm-blooded vertebrates and
      are responsible for a severe traumatic myiasis of mucosal membranes or wounds.
      This myiasis has been reported in many European areas, but for the first time was
      reported from Iran. Larvae infestation was observed in five camels out of 35
      (14.28%) around the perinea and vaginal region of camels in a herd in southwest
      of Iran. The larvae samples were collected and transferred to the laboratory of
      parasitology for identification. This is the first report of infestation of a
      camel herd (camelus dromedarius) in Iran. The treatment was performed and
      prevented the loss from camels and improved their physical condition. Although
      the myiasis is not a lethal disorder, however knowledge of the disease is
      necessary from preventive, diagnostic and curative standpoint. 

PMID- 25610588
TI  - Synophthalmia in a Holstein cross calf.
AB  - Synophthalmia is a form of cyclopia, in which some elements of two eyes are fused
      and form a single eye in the middle region of the forehead. The head of a
      Holstein female calf born from a 5-year-old cow was referred to Department of
      Pathology, School of Veterinary Medicine, Shahrekord University due to multiple
      congenital anomalies. The calf had been slaughtered immediately after birth due
      to severe respiratory distress by the owner. The calf showed multiple birth
      defects, including synophthalmia, holoprosencephaly, absence of optic chiasma,
      hypoplastic maxilla, curved mandibles, arrhinia and dental pad agenesis. A normal
      tongue protruded from the defect and small oral cavity. To our knowledge, this
      particular combination of craniofacial defects has not been previously described
      in Holstein calf. 

PMID- 25610589
TI  - The extracellular matrix: Structure, composition, age-related differences, tools
      for analysis and applications for tissue engineering.
AB  - The extracellular matrix is a structural support network made up of diverse
      proteins, sugars and other components. It influences a wide number of cellular
      processes including migration, wound healing and differentiation, all of which is
      of particular interest to researchers in the field of tissue engineering.
      Understanding the composition and structure of the extracellular matrix will aid
      in exploring the ways the extracellular matrix can be utilised in tissue
      engineering applications especially as a scaffold. This review summarises the
      current knowledge of the composition, structure and functions of the
      extracellular matrix and introduces the effect of ageing on extracellular matrix
      remodelling and its contribution to cellular functions. Additionally, the current
      analytical technologies to study the extracellular matrix and extracellular
      matrix-related cellular processes are also reviewed. 

PMID- 25610590
TI  - Growth factor and ultrasound-assisted bioreactor synergism for human mesenchymal
      stem cell chondrogenesis.
AB  - Ultrasound at 5.0 MHz was noted to be chondro-inductive, with improved SOX-9 gene
      and COL2A1 protein expression in constructs that allowed for cell-to-cell
      contact. To achieve tissue-engineered cartilage using macroporous scaffolds, it
      is hypothesized that a combination of ultrasound at 5.0 MHz and transforming
      growth factor-beta3 induces human mesenchymal stem cell differentiation to
      chondrocytes. Expression of miR-145 was used as a metric to qualitatively assess
      the efficacy of human mesenchymal stem cell conversion. Our results suggest that
      in group 1 (no transforming growth factor-beta3, no ultrasound), as anticipated,
      human mesenchymal stem cells were not efficiently differentiated into
      chondrocytes, judging by the lack of decrease in the level of miR-145 expression.
      Human mesenchymal stem cells differentiated into chondrocytes in group 2
      (transforming growth factor-beta3, no ultrasound) and group 3 (transforming
      growth factor-beta3, ultrasound) with group 3 having a 2-fold lower miR-145 when
      compared to group 2 at day 7, indicating a higher conversion to chondrocytes.
      Transforming growth factor-beta3-induced chondrogenesis with and without
      ultrasound stimulation for 14 days in the ultrasound-assisted bioreactor was
      compared and followed by additional culture in the absence of growth factors. The
      combination of growth factor and ultrasound stimulation (group 3) resulted in
      enhanced COL2A1, SOX-9, and ACAN protein expression when compared to growth
      factor alone (group 2). No COL10A1 protein expression was noted. Enhanced cell
      proliferation and glycosaminoglycan deposition was noted with the combination of
      growth factor and ultrasound stimulation. These results suggest that ultrasound
      at 5.0 MHz could be used to induce chondrogenic differentiation of mesenchymal
      stem cells for cartilage tissue engineering. 

PMID- 25610591
TI  - The first annual Drug Discovery and Development Symposium for Pulmonary
      Hypertension.

PMID- 25610592
TI  - Mechanisms regulating endothelial permeability.
AB  - The endothelial monolayer partitioning underlying tissue from blood components in
      the vessel wall maintains tissue fluid balance and host defense through
      dynamically opening intercellular junctions. Edemagenic agonists disrupt
      endothelial barrier function by signaling the opening of the intercellular
      junctions leading to the formation of protein-rich edema in the interstitial
      tissue, a hallmark of tissue inflammation that, if left untreated, causes fatal
      diseases, such as acute respiratory distress syndrome. In this review, we discuss
      how intercellular junctions are maintained under normal conditions and after
      stimulation of endothelium with edemagenic agonists. We have focused on reviewing
      the new concepts dealing with the alteration of adherens junctions after
      inflammatory stimulus. 

PMID- 25610593
TI  - Is cardiac resynchronization therapy for right ventricular failure in pulmonary
      arterial hypertension of benefit?
AB  - Pulmonary arterial hypertension is a manifestation of a group of disorders
      leading to pulmonary vascular remodeling and increased pulmonary pressures. The
      right ventricular (RV) response to chronic pressure overload consists of
      myocardial remodeling, which is in many ways similar to that seen in left
      ventricular (LV) failure. Maladaptive myocardial remodeling often leads to
      intraventricular and interventricular dyssychrony, an observation that has led to
      cardiac resynchronization therapy (CRT) for LV failure. CRT has proven to be an
      effective treatment strategy in subsets of patients with LV failure resulting in
      improvement in LV function, heart failure symptoms, and survival. Current therapy
      for pulmonary arterial hypertension is based on decreasing pulmonary vascular
      resistance, and there is currently no effective therapy targeting the right
      ventricle or maladaptive ventricular remodeling in these patients. This review
      focuses on the RV response to chronic pressure overload, its effect on
      electromechanical coupling and synchrony, and how lessons learned from left
      ventricular cardiac resynchronization might be applied as therapy for RV
      dysfunction in the context of pulmonary arterial hypertension. 

PMID- 25610594
TI  - Vascular stiffening in pulmonary hypertension: cause or consequence? (2013 Grover
      Conference series).
AB  - Recent studies have indicated that systemic arterial stiffening is a precursor to
      hypertension and that hypertension, in turn, can perpetuate arterial stiffening.
      Pulmonary artery (PA) stiffening is also well documented to occur in pulmonary
      hypertension (PH), and there is evidence that pulmonary vascular stiffness (PVS)
      may be a better predictor of outcome than pulmonary vascular resistance (PVR). We
      have hypothesized that the decreased flow-damping function of elastic PAs in PH
      likely initiates and/or perpetuates dysfunction of pulmonary microvasculature.
      Recent studies have shown that large-vessel stiffening increases flow pulsatility
      in the distal pulmonary vasculature, leading to endothelial dysfunction within a
      proinflammatory, vasoconstricting, and profibrogenic environment. The intricate
      role of stiffening-stimulated high pulsatile flow in endothelial cell dysfunction
      includes stepwise molecular events underlying PA hypertrophy, inflammation,
      endothelial-mesenchymal transition, and fibrosis. In addition to contributing to
      microenvironmental alterations of the distal vasculature, disordered proximal
      distal PA coupling likely also plays a role in increasing ventricular afterload,
      ultimately causing right ventricle (RV) dysfunction and death. Current
      therapeutic treatments do not provide a realistic approach to destiffening
      arteries and, thus, to potentially abrogating the effects of high pulsatile flow
      on the distal pulmonary vasculature or the increased work imposed by stiffening
      on the RV. Scrutinizing the effect of PA stiffening on high pulsatile flow
      induced cellular and molecular changes, and vice versa, might lead to important
      new therapeutic options that abrogate PA remodeling and PH development. With a
      clear understanding that PA stiffening may contribute to the progression of PH to
      an irreversible state by contributing to chronic microvascular damage in lungs,
      future studies should be aimed first at defining the underlying mechanisms
      leading to PA stiffening and then at improved treatment approaches based on these
      findings. 

PMID- 25610595
TI  - Pulmonary hypertension caused by pulmonary venous hypertension.
AB  - The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is
      extraordinarily variable, ranging from no impact on pulmonary vascular resistance
      (PVR) to a marked increase. The reasons for this are unknown. Both acutely
      reversible pulmonary vasoconstriction and pathological remodeling (especially
      medial hypertrophy and intimal hyperplasia) account for increased PVR when
      present. The mechanisms involved in vasoconstriction and remodeling are not
      clearly defined, but increased wall stress, especially in small pulmonary
      arteries, presumably plays an important role. Myogenic contraction may account
      for increased vascular tone and also indirectly stimulate remodeling of the
      vessel wall. Increased wall stress may also directly cause smooth muscle growth,
      migration, and intimal hyperplasia. Even long-standing and severe pulmonary
      hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an
      important clinical problem, especially because PVH due to left ventricular
      noncompliance lacks definitive therapy. The role of targeted PH therapy in
      patients with PVH-PH is unclear at this time. Most prospective studies indicate
      that these medications are not helpful or worse, but there is ample reason to
      think that a subset of patients with PVH-PH may benefit from phosphodiesterase
      inhibitors or other agents. A different approach to evaluating possible
      pharmacologic therapy for PVH-PH may be required to better define its possible
      utility. 

PMID- 25610597
TI  - Effects of acute intravenous iloprost on right ventricular hemodynamics in rats
      with chronic pulmonary hypertension.
AB  - The inotropic effects of prostacyclins in chronic pulmonary arterial hypertension
      (PAH) are unclear and may be important in directing patient management in the
      acute setting. We sought to study the effects of an acute intravenous (IV)
      infusion of iloprost on right ventricular (RV) contractility in a rat model of
      chronic PAH. Rats were treated with monocrotaline, 60 mg/kg intraperitoneally, to
      induce PAH. Six weeks later, baseline hemodynamic assessment was performed with
      pressure-volume and Doppler flow measurements. In one group of animals,
      measurements were repeated 10-15 minutes after IV infusion of a fixed dose of
      iloprost (20 MUg/kg). A separate group of rats underwent dose-response
      assessment. RV contractility and RV-pulmonary artery coupling were assessed by
      the end-systolic pressure-volume relationship (ESPVR) and end-systolic
      elastance/effective arterial elastance (Ees/Ea). RV cardiomyocytes were isolated,
      and intracellular cAMP (cyclic adenosine monophosphate) concentration was
      measured with a cAMP-specific enzyme immunoassay kit. Animals had evidence of PAH
      and RV hypertrophy. Right ventricle/(left ventricle + septum) weight was 0.40 +/-
      0.03. RV systolic pressure (RVSP) was 39.83 +/- 1.62 mmHg. Administration of
      iloprost demonstrated an increase in the slope of the ESPVR from 0.29 +/- 0.02 to
      0.42 +/- 0.05 (P < .05). Ees/Ea increased from 0.63 +/- 0.07 to 0.82 +/- 0.06 (P
      < .05). The RV contractility index (max dP/dt normalized for instantaneous
      pressure) increased from 94.11 to 114.5/s (P < .05), as did the RV ejection
      fraction, from 48.0% to 52.5% (P < .05). This study suggests a positive inotropic
      effect of iloprost on a rat model of chronic PAH. 

PMID- 25610596
TI  - Schistosomiasis-associated pulmonary hypertension.
AB  - Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and
      Asia; it is estimated that close to 20 million people worldwide have a severe
      form of the disease. The chronic form can affect the gastrointestinal system and
      lead to hepatosplenic disease, and it may cause cardiopulmonary complications,
      including pulmonary hypertension. The exact pathogenesis of schistosomiasis
      associated pulmonary hypertension (Sch-PH) remains unclear, although several
      mechanisms, including parasitic arterial embolization, pulmonary arteriopathy,
      and portopulmonary hypertension-like pathophysiology, have been suggested. The
      immunopathology of the disease is also unclear, although there are similarities
      with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally,
      the treatment of Sch-PH has not been well studied. There is some evidence on
      treating the underlying infection, with unclear effect on Sch-PH, and advanced
      PAH therapies are now being suggested, but more studies are needed to confirm
      their efficacy. 

PMID- 25610598
TI  - The Sugen 5416/hypoxia mouse model of pulmonary hypertension revisited: long-term
      follow-up.
AB  - The combination of a vascular endothelial growth factor receptor antagonist,
      Sugen 5416 (SU5416), and chronic hypoxia is known to cause pronounced pulmonary
      hypertension (PH) with angioobliterative lesions in rats and leads to exaggerated
      PH in mice as well. We sought to determine whether weekly SU5416 injections
      during 3 weeks of hypoxia leads to long-term development of angioobliterative
      lesions and sustained or progressive PH in mice. Male C57BL/6J mice were injected
      with SU5416 (SuHx) or vehicle (VehHx) weekly during 3 weeks of exposure to 10%
      oxygen. Echocardiographic and invasive measures of hemodynamics and pulmonary
      vascular morphometry were performed after the 3-week hypoxic exposure and after
      10 weeks of recovery in normoxia. SuHx led to higher right ventricular (RV)
      systolic pressure and RV hypertrophy than VehHx after 3 weeks of hypoxia. Ten
      weeks after hypoxic exposure, RV systolic pressure decreased but remained
      elevated in SuHx mice compared with VehHx or normoxic control mice, but RV
      hypertrophy had resolved. After 3 weeks of hypoxia and 10 weeks of follow-up in
      normoxia, tricuspid annular plane systolic excursion was significantly decreased,
      indicating decreased systolic RV function. Very few angioobliterative lesions
      were found at the 10-week follow-up time point in SuHx mouse lungs. In
      conclusion, SU5416 combined with 3 weeks of hypoxia causes a more profound PH
      phenotype in mice than hypoxia alone. PH persists over 10 weeks of normoxic
      follow-up in SuHx mice, but significant angioobliterative lesions do not occur,
      and neither PH nor RV dysfunction worsens. The SuHx mouse model is a useful
      adjunct to other PH models, but the search will continue for a mouse model that
      better recapitulates the human phenotype. 

PMID- 25610599
TI  - Impaired exercise capacity following atrial septal defect closure: an invasive
      study of the right heart and pulmonary circulation.
AB  - Patients with early repair of an isolated atrial septal defect (ASD) are expected
      to have unremarkable right ventricular (RV) and pulmonary circulation physiology.
      Some studies, however, suggest persistent functional impairment. We aimed to
      examine the role of abnormal RV and pulmonary vascular response to exercise in
      patients who had undergone ASD closure. Using a previously published data set, we
      reviewed invasive exercise cardiopulmonary testing with right-sided hemodynamic
      data for 12 asymptomatic patients who had undergone ASD closure. The 5 (42%)
      patients with impaired maximal oxygen uptake ([Formula: see text]) were older and
      exhibited a lower peak cardiac index (5.6 +/- 0.8 vs. 9.0 +/- 1.2 L/min/m(2); P =
      .005) because of abnormal stroke volume augmentation (+3.2 +/- 3.9 vs. +17.4 +/-
      10.2 mL/m(2); P = .02). While all resting hemodynamic variables were similar,
      patients with low [Formula: see text] tended to have abnormal total pulmonary
      vascular resistance change during exercise (+11% +/- 41% vs. -28% +/- 26%; P =
      .06) and had a steeper relation between mean pulmonary arterial pressure and
      cardiac index (5.8 +/- 0.6 vs. 2.2 +/- 0.1 L/min/m(2); P = .02). The increase in
      peak mean RV power during exercise was also significantly lower in the impaired
      [Formula: see text] patients (4.7 +/- 1.6 vs. 7.6 +/- 2.1 J/s; P = .04). As
      described in the original study, despite normal resting hemodynamics, a subset of
      asymptomatic patients with repaired ASD had diminished exercise capacity. Our
      analysis allows us to conclude that this is due to a combination of abnormal
      pulmonary vascular response to exercise and impaired RV function. 

PMID- 25610600
TI  - Obesity-related pulmonary arterial hypertension in rats correlates with increased
      circulating inflammatory cytokines and lipids and with oxidant damage in the
      arterial wall but not with hypoxia.
AB  - Obesity is causally linked to a number of comorbidities, including cardiovascular
      disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to
      pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long
      believed that obesity-related PAH was the result of hypoventilation and hypoxia
      due to the increased mechanical load of excess body fat. However, in recent years
      it has been proposed that the metabolic and inflammatory disturbances of obesity
      may also play a role in the development of PAH. To determine whether PAH develops
      in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and
      pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity
      (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding
      (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of
      distal arterioles, and elevated PA pressure, accompanied by right ventricular
      (RV) hypertrophy. PA thickening and distal neomuscularization were also observed
      in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia
      was detected in either model, nor was there a correlation between blood glucose
      or insulin levels and PAH. However, circulating inflammatory cytokine levels were
      increased with high-fat feeding or calorie overload, and hyperlipidemia and
      oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We
      conclude that hyperlipidemia and peripheral inflammation correlate with the
      development of PAH in obese subjects. Obesity-related inflammation may predispose
      to PAH even in the absence of hypoxia. 

PMID- 25610601
TI  - Interleukin 13- and interleukin 17A-induced pulmonary hypertension phenotype due
      to inhalation of antigen and fine particles from air pollution.
AB  - Pulmonary hypertension has a marked detrimental effect on quality of life and
      life expectancy. In a mouse model of antigen-induced pulmonary arterial
      remodeling, we have recently shown that coexposure to urban ambient particulate
      matter (PM) significantly increased the thickening of the pulmonary arteries and
      also resulted in significantly increased right ventricular systolic pressures.
      Here we interrogate the mechanism and show that combined neutralization of
      interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right
      ventricular systolic pressure, the circumferential muscularization of pulmonary
      arteries, and the molecular change in the right ventricle. Surprisingly, our data
      revealed a protective role of IL-17A for the antigen- and PM-induced severe
      thickening of pulmonary arteries. This protection was due to the inhibition of
      the effects of IL-13, which drove this response, and the expression of
      metalloelastase and resistin-like molecule alpha. However, the latter was
      redundant for the arterial thickening response. Anti-IL-13 exacerbated airway
      neutrophilia, which was due to a resulting excess effect of IL-17A, confirming
      concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs
      of animals exposed to antigen and PM. Our experiments also identified IL-13/IL
      17A-independent molecular reprogramming in the lungs induced by exposure to
      antigen and PM, which indicates a risk for arterial remodeling and protection
      from arterial constriction. Our study points to IL-13- and IL-17A-coinduced
      inflammation as a new template for biomarkers and therapeutic targeting for the
      management of immune response-induced pulmonary hypertension. 

PMID- 25610602
TI  - Response to pulmonary arterial hypertension drug therapies in patients with
      pulmonary arterial hypertension and cardiovascular risk factors.
AB  - The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence
      of cardiovascular (CV) risk factors are increasing. We sought to determine
      whether the response to drug therapy was influenced by CV risk factors in PAH
      patients. We studied consecutive incident PAH patients (n = 146) between January
      1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV
      group included patients with no CV risk factors (obesity, systemic hypertension,
      type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic
      valve disease, and coronary artery disease), and the PAH-CV group included
      patients with at least one. The response to PAH treatment was analyzed in all the
      patients who received PAH drug therapy. The PAH-No CV group included 43 patients,
      and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were
      younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16
      patients (37%) improved on treatment and 27 (63%) did not improve, compared with
      11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after
      adjustment for age). There was no difference in survival at 30 months (P =
      0.218). In conclusion, in addition to older age, CV risk factors may predict a
      reduced response to PAH drug therapy in patients with PAH. 

PMID- 25610603
TI  - Variability in hemodynamic evaluation of pulmonary hypertension at large referral
      centers.
AB  - Despite consensus guidelines for right heart catheterization (RHC) in the
      diagnosis of pulmonary arterial hypertension (PAH), considerable differences
      exist in the performance of RHC, interpretation of hemodynamic data, and
      frequency of RHC performance in patients with established disease. These
      differences may lead to variability in diagnosis or treatment of PAH. We sought
      to gather information on the standard practice of RHC for the diagnosis and
      management of PAH from experienced pulmonary vascular disease specialists. We
      developed a semiquantitative online survey of diagnosis and treatment patterns of
      pulmonary hypertension and distributed it to physicians at pulmonary hypertension
      centers in the United States. Thirty of 50 physicians completed the survey: 20
      pulmonologists and 10 cardiologists, all of whom reported treating >100 patients
      with PAH in the past year. All respondents perform RHC in >=90% of patients with
      suspected PAH. All physicians determine the pulmonary wedge pressure at end
      expiration; however, only half of respondents personally review tracings.
      Physicians differed in frequency of vasodilator testing (8 of 24 performed
      testing in >90% of patients with PAH), fluid challenge and exercise (19 of 30
      performed testing in <25% of patients with PAH for both). Most physicians (70%)
      report repeating RHC between 6 months and 1 year after PAH treatment initiation.
      Variability exists in the interpretation of hemodynamic tracings and performance
      of vasodilator, fluid, and exercise challenges in the management of PAH by
      experienced physicians in the United States. Additional consensus guidelines
      delineating appropriate adjunctive testing to standardize the diagnosis of PAH
      are needed. 

PMID- 25610604
TI  - Time-domain analysis of heart sound intensity in children with and without
      pulmonary artery hypertension: a pilot study using a digital stethoscope.
AB  - We studied digital stethoscope recordings in children undergoing simultaneous
      catheterization of the pulmonary artery (PA) to determine whether time-domain
      analysis of heart sound intensity would aid in the diagnosis of PA hypertension
      (PAH). Heart sounds were recorded and stored in .wav mono audio format. We
      performed recordings for 20 seconds with sampling frequencies of 4,000 Hz at the
      second left intercostal space and the cardiac apex. We used programs written in
      the MATLAB 2010b environment to analyze signals. We annotated events representing
      the first (S1) and second (S2) heart sounds and the aortic (A2) and pulmonary
      (P2) components of S2. We calculated the intensity (I) of the extracted event
      area (x) as [Formula: see text], where n is the total number of heart sound
      samples in the extracted event and k is A2, P2, S1, or S2. We defined PAH as mean
      PA pressure (mPAp) of at least 25 mmHg with PA wedge pressure of less than 15
      mmHg. We studied 22 subjects (median age: 6 years [range: 0.25-19 years], 13
      female), 11 with PAH (median mPAp: 55 mmHg [range: 25-97 mmHg]) and 11 without
      PAH (median mPAp: 15 mmHg [range: 8-24 mmHg]). The P2?A2 (P = .0001) and P2?S2 (P
      = .0001) intensity ratios were significantly different between subjects with and
      those without PAH. There was a linear correlation (r > 0.7) between the P2?S2 and
      P2?A2 intensity ratios and mPAp. We found that the P2?A2 and P2?S2 intensity
      ratios discriminated between children with and those without PAH. These findings
      may be useful for developing an acoustic device to diagnose PAH. 

PMID- 25610605
TI  - Pulmonary hypertension and the right ventricle-thinking outside the box (Third
      International Right Heart Failure Summit, part 1).
AB  - The Third International Right Heart Failure Summit (Boston, MA) convened a group
      of international clinical and scientific experts in pulmonary vascular disease
      and right heart disease to explore cutting-edge developments in the mechanisms
      and clinical management of right-sided cardiovascular disease. The symposium was
      organized into three distinct sessions, the first of which was titled "Pulmonary
      Hypertension and the Right Ventricle-Thinking outside the Box" and will be the
      focus of this review. Three internationally renowned experts in pulmonary
      hypertension and right heart disease-Drs. Stuart Rich, Sean Gaine, and Harm
      Bogaard-each delivered provocative lectures. The first lecture, by Dr. Rich, was
      titled "Current Classification for Pulmonary Hypertension-Why Are We Ignoring the
      Structural Basis of the Disease?" Rich focused on the current classification
      system of pulmonary hypertension and provided a unique historical perspective. He
      also addressed the need to evolve the prevailing conceptual framework of our
      approach to pulmonary vascular diseases and right ventricular dysfunction,
      including the future design of pulmonary hypertension clinical trials. Dr. Gaine
      delivered the second lecture, titled "Treatment Algorithm for Pulmonary
      Hypertension: Tunnel Vision of our Current Approach." Gaine emphasized the
      tripartite model of pulmonary hypertension management, namely, supportive
      measures, pharmacologic therapy, and rescue therapy. Specifically, he detailed
      how each of these entities is changing as our understanding of the unmet needs in
      the field of pulmonary hypertension is becoming increasingly apparent. Finally,
      Dr. Bogaard provided a lecture titled "Treating Right Heart Failure: Why Does the
      Art of Medicine Lead the Science?" Bogaard provided a stimulating review of
      cutting-edge translational research of right ventricular function and
      dysfunction. In particular, he described a variety of molecular and cellular
      changes that occur in the hypertrophied right ventricle and contrasted those
      changes that may be adaptive from those that are maladaptive and may be potential
      therapeutic targets. 

PMID- 25610606
TI  - Emerging hemodynamic signatures of the right heart (Third International Right
      Heart Failure Summit, part 2).
AB  - Despite the importance of preserved right ventricular structure and function with
      respect to outcome across the spectrum of lung, cardiac, and pulmonary vascular
      diseases, only recently have organized efforts developed to consider the
      pulmonary vascular-right ventricular apparatus as a specific unit within the
      larger context of cardiopulmonary pathophysiology. The Third International Right
      Heart Failure Summit (Boston, MA) was a multidisciplinary event dedicated to
      promoting a dialogue about the scientific and clinical basis of right heart
      disease. The current review provides a synopsis of key discussions presented
      during the section of the summit titled "Emerging Hemodynamic Signatures of the
      Right Heart." Specifically, topics emphasized in this element of the symposium
      included (1) the effects of pulmonary vascular dysfunction at rest or provoked by
      exercise on the right ventricular pressure-volume relationship, (2) the role of
      pressure-volume loop analysis as a method to characterize right ventricular
      inefficiency and predict right heart failure, and (3) the importance of a systems
      biology approach to identifying novel factors that contribute to pathophenotypes
      associated with pulmonary arterial hypertension and/or right ventricular
      dysfunction. Collectively, these concepts frame a forward-thinking paradigm shift
      in the approach to right heart disease by emphasizing factors that regulate the
      transition from adaptive to maladaptive right ventricular-pulmonary vascular
      (patho)physiology. 

PMID- 25610607
TI  - Transplantation in end-stage pulmonary hypertension (Third International Right
      Heart Failure Summit, part 3).
AB  - The Third International Right Heart Summit was organized for the purpose of
      bringing an interdisciplinary group of expert physician-scientists together to
      promote dialogue involving emerging concepts in the unique pathophysiology,
      clinical manifestation, and therapies of pulmonary vascular disease (PVD) and
      right heart failure (RHF). This review summarizes key ideas addressed in the
      section of the seminar entitled "Transplantation in End-Stage Pulmonary
      Hypertension." The first segment focused on paradigms of recovery for the failing
      right ventricle (RV) within the context of lung-alone versus dual-organ heart
      lung transplantation. The subsequent 2-part section was devoted to emerging
      concepts in RV salvage therapy. A presentation of evolving cell-based therapy for
      the reparation of diseased tissue was followed by a contemporary perspective on
      the role of mechanical circulatory support in the setting of RV failure. The
      final talk highlighted cutting-edge research models utilizing stem cell biology
      to repair diseased tissue in end-stage lung disease-a conceptual framework within
      which new therapies for PVD have potential to evolve. Together, these provocative
      talks provided a novel outlook on how the treatment of PVD and RHF can be
      approached. 

PMID- 25610608
TI  - Pulmonary arterial hypertension in a patient with Cowden syndrome and the PTEN
      mutation.
AB  - The pathogenesis of pulmonary arterial hypertension (PAH) exhibits many
      neoplastic-like features. Cowden syndrome is a difficult-to-recognize heritable
      cancer syndrome caused by a germline mutation in the phosphatase-and-tensin
      homolog deleted on the chromosome 10 (PTEN) gene. PTEN regulation has been
      implicated in cancer development and, more recently, PAH pathogenesis. Here we
      report a case of PAH in a patient with Cowden syndrome and the response to
      pulmonary vasodilators. 

PMID- 25610609
TI  - Pulmonary hypertension in POEMS syndrome: resolution following radiotherapy.
AB  - Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary artery
      pressure (mPAP) >=25 mmHg. It may be idiopathic or arise as a consequence of a
      number of diverse conditions. PH has been reported in association with POEMS
      syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell
      disorder, and skin changes), with reversal following systemic treatment with
      corticosteroids. We report a case of pulmonary hypertension associated with POEMS
      syndrome treated with radical radiotherapy locally to bone lesions with
      resolution of systemic disease. 

PMID- 25610611
TI  - A survey of management practices on Irish dairy farms with emphasis on risk
      factors for Johne's disease transmission.
AB  - BACKGROUND: Johne's disease (JD) is a chronic granulomatous enteritis affecting
      ruminants. A number of farm management practices are associated with increased
      risk of JD transmission. The aim of the current study was to document JD-related
      management practices currently employed on Irish dairy farms. Survey questions
      focused on calving area (CA), calf and manure management. Independent variables
      (region, calving-season, enterprise type, herd size and biosecurity status) were
      used to examine influences on JD associated dependent variables (survey
      questions). Additionally general biosecurity practices were also examined.
      RESULTS: Results showed management practices implemented by Irish dairy farmers
      pose a high risk of JD transmission. Of the farmers surveyed, 97% used the CA for
      more than one calving, 73.5% and 87.8% pooled colostrum and milk respectively,
      33.7% never cleaned the CA between calving's, and 56.6% used the CA for isolating
      sick cows. Survey results also highlighted that larger herds were more likely to
      engage in high risk practices for JD transmission, such as pooling colostrum (OR
      4.8) and overcrowding the CA (OR 7.8). Larger herds were also less likely than
      smaller herds to clean the CA (OR 0.28), a practice also considered of risk in
      the transmission of JD. CONCLUSION: Many management practices associated with
      risk of JD transmission were commonly applied on Irish dairy farms. Larger herds
      were more likely to engage in high risk practices for JD transmission. Control
      programmes should incorporate educational tools outlining the pathogenesis and
      transmission of JD to highlight the risks associated with implementing certain
      management practices with regard to JD transmission.

PMID- 25610613
TI  - Emergency endovascular management of the common femoral artery rupture due to
      radiotherapy for scrotal carcinoma.
AB  - We describe the case of a 72-year-old man with massive hemorrhage and shock
      resulting from rupture of the left common femoral artery as a complication of
      radiotherapy in the groin for cancer of the scrotum. This complication is
      extremely rare, presents dramatically, and is usually fatal. The patient was
      successfully treated with a stent graft deployment in order to achieve immediate
      hemostasis maintaining blood flow to the leg. Open surgery is not ideal in those
      cases especially when there is extensive tumor involvement of the groin causing
      altered anatomy and increasing the risk of re-bleeding. 

PMID- 25610612
TI  - Diagnosis and management of primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder with
      defective structure and/or function of motile cilia/flagella, causing chronic
      upper and lower respiratory tract infections, fertility problems, and disorders
      of organ laterality. Diagnosing PCD requires a combined approach utilizing
      characteristic phenotypes and complementary methods for detection of defects of
      ciliary function and ultrastructure, measurement of nasal nitric oxide and
      genetic testing. Currently, biallelic mutations in 31 different genes have been
      linked to PCD allowing a genetic diagnosis in approximately ~ 60% of cases.
      Management includes surveillance of pulmonary function, imaging, and microbiology
      of upper and lower airways in addition to daily airway clearance and prompt
      antibiotic treatment of infections. Early referral to specialized centers that
      use a multidisciplinary approach is likely to improve outcomes. Currently,
      evidence-based knowledge on PCD care is missing let alone management guidelines.
      Research and clinical investigators, supported by European and North American
      patient support groups, have joined forces under the name of BESTCILIA, a
      European Commission funded consortium dedicated to improve PCD care and
      knowledge. Core programs of this network include the establishment of an
      international PCD registry, the generation of disease specific PCD quality of
      life questionnaires, and the first randomized controlled trial in PCD. 

PMID- 25610614
TI  - Imaging findings of Gorlin-Goltz syndrome.
AB  - A 15-year-old girl was referred to a dentist complaining of parageusia, bad taste
      in the mouth, which started 9 months ago. Panoramic X-ray and non-enhanced
      computed tomography scan revealed multiple bilateral unilocular cysts in the
      mandible and maxilla, along with calcification of anterior part of the falx
      cerebri. She was eventually diagnosed with Gorlin-Goltz syndrome based on imaging
      and histopathologic finding of keratocystic odontogenic tumor. 

PMID- 25610615
TI  - Multimodal MR imaging of acute and subacute experimental traumatic brain injury:
      Time course and correlation with cerebral energy metabolites.
AB  - BACKGROUND: Traumatic brain injury (TBI) is one of the leading causes of death
      and permanent disability world-wide. The predominant cause of death after TBI is
      brain edema which can be quantified by non-invasive diffusion-weighted magnetic
      resonance imaging (DWI). PURPOSE: To provide a better understanding of the early
      onset, time course, spatial development, and type of brain edema after TBI and to
      correlate MRI data and the cerebral energy state reflected by the metabolite
      adenosine triphosphate (ATP). MATERIAL AND METHODS: The spontaneous development
      of lateral fluid percussion-induced TBI was investigated in the acute (6 h),
      subacute (48 h), and chronic (7 days) phase in rats by MRI of quantitative T2 and
      apparent diffusion coefficient (ADC) mapping as well as perfusion was combined
      with ATP-specific bioluminescence imaging and histology. RESULTS: An induced TBI
      led to moderate to mild brain damages, reflected by transient, pronounced
      development of vasogenic edema and perfusion reduction. Heterogeneous ADC
      patterns indicated a parallel, but mixed expression of vasogenic and cytotoxic
      edema. Cortical ATP levels were reduced in the acute and subacute phase by 13%
      and 27%, respectively, but were completely normalized at 7 days after injury.
      CONCLUSION: The partial ATP reduction was interpreted to be partially caused by a
      loss of neurons in parallel with transient dilution of the regional ATP
      concentration by pronounced vasogenic edema. The normalization of energy
      metabolism after 7 days was likely due to infiltrating glia and not to recovery.
      The MRI combined with metabolite measurement further improves the understanding
      and evaluation of brain damages after TBI.

PMID- 25610616
TI  - Herniation of uncus and parahippocampal gyrus: an accidental finding on magnetic
      resonance imaging of cerebrum.
AB  - Idiopathic herniation of uncus and parahippocampal gyrus into the ambient cistern
      is a very rare entity, which could be mistaken for other pathology such as tumor.
      To the best of our knowledge, two prior cases of this kind of herniation have
      been described. One of these cases was with associated symptomatology and other
      abnormalities, and the other was characterized as idiopathic. In this case
      report, we report a case of accidental finding of a herniation of uncus and
      parahippocampal gyrus into the ambient cistern, without any other accompanying
      abnormalities, well depicted by magnetic resonance imaging without further
      necessity for surgical brain intervention. 

PMID- 25610618
TI  - Acta Radiologica Short Reports to be renamed Acta Radiologica Open.

PMID- 25610619
TI  - IUCrJ celebrates its first year of publication.
AB  - IUCrJ is a fully open-access journal that publishes high-quality structural
      science papers. It has had a successful first year of publication. 

PMID- 25610617
TI  - Imaging pitfalls, normal anatomy, and anatomical variants that can simulate
      disease on cardiac imaging as demonstrated on multidetector computed tomography.
AB  - Advances in computed tomography have led to continuous improvement in cardiac
      imaging. Dedicated postprocessing capabilities, faster scan times, and cardiac
      gating methods reveal details of normal cardiac anatomy and anatomic variants
      that can mimic pathologic conditions. This article will review normal cardiac
      anatomy and variants that can mimic disease. Radiologists should be familiar with
      normal cardiac anatomy and anatomic variants to avoid misinterpretation of normal
      findings for pathologic processes. 

PMID- 25610620
TI  - Serial crystallography for the masses?
AB  - Serial crystallography should be possible with a much wider range of radiation
      sources as Ayyer et al. [IUCrJ (2015), 2, 29-34] show that crystallographic
      intensities can be recovered from randomly oriented frames which are too sparse
      for indexing. 

PMID- 25610621
TI  - Photocrystallography reveals new metastable nitrosyl linkage isomers in the solid
      state.
AB  - Using the combined techniques of photocrystallography and infrared spectroscopy
      is a very powerful method for generating and establishing the structures of
      metastable linkage isomers in the solid state as exemplified by the work of
      Casaretto et al. [IUCrJ (2015), 2, 35-44] on [RuCl(NO)2(PPh3)2]BF4. 

PMID- 25610622
TI  - Solving difficult structures with electron diffraction.
AB  - Precession electron diffraction has solved a long-standing challenge in electron
      diffraction. Further progress promises a general technique for structure
      determination of difficult crystals. 

PMID- 25610623
TI  - In-depth analysis of subclass-specific conformational preferences of IgG
      antibodies.
AB  - IgG subclass-specific differences in biological function and in vitro stability
      are often referred to variations in the conformational flexibility, while this
      flexibility has rarely been characterized. Here, small-angle X-ray scattering
      data from IgG1, IgG2 and IgG4 antibodies, which were designed with identical
      variable regions, were thoroughly analysed by the ensemble optimization method.
      The extended analysis of the optimized ensembles through shape clustering reveals
      distinct subclass-specific conformational preferences, which provide new insights
      for understanding the variations in physical/chemical stability and biological
      function of therapeutic antibodies. Importantly, the way that specific
      differences in the linker region correlate with the solution structure of intact
      antibodies is revealed, thereby visualizing future potential for the rational
      design of antibodies with designated physicochemical properties and tailored
      effector functions. In addition, this advanced computational approach is
      applicable to other flexible multi-domain systems and extends the potential for
      investigating flexibility in solutions of macromolecules by small-angle X-ray
      scattering. 

PMID- 25610624
TI  - Rochelle salt - a structural reinvestigation with improved tools. I. The high
      temperature para-electric phase at 308 K.
AB  - The crystal structure of the high-temperature paraelectric phase of Rochelle salt
      (K(+).Na(+).C4H4O6 (2-).4H2O) at 308 K has been reinvestigated using synchrotron
      X-ray diffraction with refinement parameters R(int) = 0.0123, final
      (shift/e.s.d.)max = 0.019, R 1(all) = 0.0371 and wR 2(all) = 0.0608. The
      application of a new gas-flow sample cell designed to control both temperature
      and relative humidity permitted collection of data of excellent quality and
      enabled unrestrained refinement of all parameters, including those of the
      isotropic hydrogen atoms. A precise description of the structure has ensued. One
      K atom is disordered between two symmetry-equivalent sites; three O atoms in
      three of the four water molecules exhibit very strong anisotropy. Refining one O
      atom as a split atom was successful, yielding small improvements in the bonding
      parameters of several H atoms. The H atoms of all water molecules behave as
      single pairs. Their final U values are of moderate magnitude indicating that
      these atoms do not participate in the anisotropy of the parent O atoms. It is
      suggested that the three water O atoms are in part statically disordered, while
      the bonded H atoms are not. Except for the split K atom and the three water O
      atoms there is no evidence of general disorder in the structure. 

PMID- 25610625
TI  - Determination of crystallographic intensities from sparse data.
AB  - X-ray serial microcrystallography involves the collection and merging of frames
      of diffraction data from randomly oriented protein microcrystals. The number of
      diffracted X-rays in each frame is limited by radiation damage, and this number
      decreases with crystal size. The data in the frame are said to be sparse if too
      few X-rays are collected to determine the orientation of the microcrystal. It is
      commonly assumed that sparse crystal diffraction frames cannot be merged, thereby
      setting a lower limit to the size of microcrystals that may be merged with a
      given source fluence. The EMC algorithm [Loh & Elser (2009 ?), Phys. Rev. E, 80,
      026705] has previously been applied to reconstruct structures from sparse
      noncrystalline data of objects with unknown orientations [Philipp et al. (2012
      ?), Opt. Express, 20, 13129-13137; Ayyer et al. (2014 ?), Opt. Express, 22, 2403
      2413]. Here, it is shown that sparse data which cannot be oriented on a per-frame
      basis can be used effectively as crystallographic data. As a proof-of-principle,
      reconstruction of the three-dimensional diffraction intensity using sparse data
      frames from a 1.35 kDa molecule crystal is demonstrated. The results suggest that
      serial microcrystallography is, in principle, not limited by the fluence of the X
      ray source, and collection of complete data sets should be feasible at, for
      instance, storage-ring X-ray sources. 

PMID- 25610626
TI  - Multiple light-induced NO linkage isomers in the dinitrosyl complex
      [RuCl(NO)2(PPh3)2]BF4 unravelled by photocrystallographic and IR analysis.
AB  - Multiple light-induced reversible metastable NO linkage isomers (PLIs) have been
      detected in the dinitrosyl compound [RuCl(NO)2(PPh3)2]BF4 by a combination of
      photocrystallographic and IR analysis. The IR signature of three PLI states has
      been clearly identified, with estimated populations of 59% (PLI-1), 8% (PLI-2)
      and 5% (PLI-3) for a total population of the metastable state of 72%. The
      structural configuration of the major component (PLI-1) has been derived by X-ray
      photocrystallography. In the ground state, the structure is characterized by a
      bent and a linear nitrosyl, the bent one being oriented towards the linear
      equatorial nitrosyl with an Ru-N-O angle of 133.88 (9) degrees . X-ray Fourier
      difference maps indicate a selectivity of the photo-isomerization process in PLI
      1: only the bent NO ligand changes its position, while the linear NO is
      unaffected. After irradiation at 405 nm, the orientation is changed by rotation
      towards the Cl ligand opposite the linear NO, with an Ru-N-O angle in this new
      position of 109 (1) degrees . The photocrystallographic analysis provides
      evidence that, in the photo-induced metastable state, the bent NO group is
      attached to the Ru atom through the N atom (Ru-N-O), rather than in an
      isonitrosyl Ru-O-N binding mode. In the IR spectra, the asymmetric NO vibrational
      band shifts by -33 cm(-1) to a lower value, whereas the symmetric band splits and
      shifts by 5 cm(-1) to a higher value and by -8 cm(-1) to a lower value. The down
      shift is a clear indication of the structural change, and the small upward shift
      in response to the new electronic configuration of the metastable structure.
      Variable-temperature IR kinetic measurements in the range 80-114 K show that the
      decay of the PLI-1 state follows an Arrhenius behaviour with an activation energy
      of 0.22 eV. 

PMID- 25610628
TI  - Cascading time evolution of dissipative structures leading to unique crystalline
      textures.
AB  - This article reports unique pattern formation processes and mechanisms via
      crystallization of materials under external flow fields as one of the general
      problems of open nonequilibrium phenomena in statistical physics. The external
      fields effectively reduce step-by-step the exceedingly large free energy barriers
      associated with the reduction of the enormously large entropy necessary for
      crystallization into unique crystalline textures in the absence of the fields.
      The cascading reduction of the free energy barrier was discovered to be achieved
      as a consequence of a cascading evolution of a series of dissipative structures.
      Moreover, this cascading pattern evolution obeys the Ginzburg-Landau law. It
      first evolves a series of large-length-scale amorphous precursors driven by
      liquid-liquid phase separation under a relatively low bulk stress and then small
      length-scale structures driven by a large local stress concentrated on the
      heterogeneous amorphous precursors, eventually leading to the formation of unique
      crystalline textures which cannot be developed free from the external fields.
      Here the multi-length-scale heterogeneous structures developed in the amorphous
      precursors play a dominant role in the triggering of the crystallization in the
      local regions subjected to a large stress concentration even under a relatively
      small applied bulk stress. 

PMID- 25610629
TI  - A modulation wave approach to the order hidden in disorder.
AB  - The usefulness of a modulation wave approach to understanding and interpreting
      the highly structured continuous diffuse intensity distributions characteristic
      of the reciprocal spaces of the very large family of inherently flexible
      materials which exhibit ordered 'disorder' is pointed out. It is shown that both
      longer range order and truly short-range order are simultaneously encoded in
      highly structured diffuse intensity distributions. The long-range ordered crystal
      chemical rules giving rise to such diffuse distributions are highlighted, along
      with the existence and usefulness of systematic extinction conditions in these
      types of structured diffuse distributions. 

PMID- 25610627
TI  - Data to knowledge: how to get meaning from your result.
AB  - Structural and functional studies require the development of sophisticated 'Big
      Data' technologies and software to increase the knowledge derived and ensure
      reproducibility of the data. This paper presents summaries of the Structural
      Biology Knowledge Base, the VIPERdb Virus Structure Database, evaluation of
      homology modeling by the Protein Model Portal, the ProSMART tool for conformation
      independent structure comparison, the LabDB 'super' laboratory information
      management system and the Cambridge Structural Database. These techniques and
      technologies represent important tools for the transformation of crystallographic
      data into knowledge and information, in an effort to address the problem of non
      reproducibility of experimental results. 

PMID- 25610630
TI  - Perspectives on Li and transition metal fluoride phosphates as cathode materials
      for a new generation of Li-ion batteries.
AB  - To satisfy the needs of rapidly growing applications, Li-ion batteries require
      further significant improvements of their key properties: specific energy and
      power, cyclability, safety and costs. The first generation of cathode materials
      for Li-ion batteries based on mixed oxides with either spinel or rock-salt
      derivatives has already been widely commercialized, but the potential to improve
      the performance of these materials further is almost exhausted. Li and transition
      metal inorganic compounds containing different polyanions are now considered as
      the most promising cathode materials for the next generation of Li-ion batteries.
      Further advances in cathode materials are considered to lie in combining
      different anions [such as (XO4) (n-) and F(-)] in the anion sublattice, which is
      expected to enhance the specific energy and power of these materials. This review
      focuses on recent advances related to the new class of cathode materials for Li
      ion batteries containing phosphate and fluoride anions. Special attention is
      given to their crystal structures and the relationships between structure and
      properties, which are important for their possible practical applications. 

PMID- 25610631
TI  - Macromolecular ab initio phasing enforcing secondary and tertiary structure.
AB  - Ab initio phasing of macromolecular structures, from the native intensities alone
      with no experimental phase information or previous particular structural
      knowledge, has been the object of a long quest, limited by two main barriers:
      structure size and resolution of the data. Current approaches to extend the scope
      of ab initio phasing include use of the Patterson function, density modification
      and data extrapolation. The authors' approach relies on the combination of
      locating model fragments such as polyalanine alpha-helices with the program
      PHASER and density modification with the program SHELXE. Given the difficulties
      in discriminating correct small substructures, many putative groups of fragments
      have to be tested in parallel; thus calculations are performed in a grid or
      supercomputer. The method has been named after the Italian painter Arcimboldo,
      who used to compose portraits out of fruit and vegetables. With ARCIMBOLDO, most
      collections of fragments remain a 'still-life', but some are correct enough for
      density modification and main-chain tracing to reveal the protein's true
      portrait. Beyond alpha-helices, other fragments can be exploited in an analogous
      way: libraries of helices with modelled side chains, beta-strands, predictable
      fragments such as DNA-binding folds or fragments selected from distant homologues
      up to libraries of small local folds that are used to enforce nonspecific
      tertiary structure; thus restoring the ab initio nature of the method. Using
      these methods, a number of unknown macromolecules with a few thousand atoms and
      resolutions around 2 A have been solved. In the 2014 release, use of the program
      has been simplified. The software mediates the use of massive computing to
      automate the grid access required in difficult cases but may also run on a single
      multicore workstation (http://chango.ibmb.csic.es/ARCIMBOLDO_LITE) to solve
      straightforward cases. 

PMID- 25610632
TI  - Advanced grazing-incidence techniques for modern soft-matter materials analysis.
AB  - The complex nano-morphology of modern soft-matter materials is successfully
      probed with advanced grazing-incidence techniques. Based on grazing-incidence
      small- and wide-angle X-ray and neutron scattering (GISAXS, GIWAXS, GISANS and
      GIWANS), new possibilities arise which are discussed with selected examples. Due
      to instrumental progress, highly interesting possibilities for local structure
      analysis in this material class arise from the use of micro- and nanometer-sized
      X-ray beams in micro- or nanofocused GISAXS and GIWAXS experiments. The
      feasibility of very short data acquisition times down to milliseconds creates
      exciting possibilities for in situ and in operando GISAXS and GIWAXS studies.
      Tuning the energy of GISAXS and GIWAXS in the soft X-ray regime and in time-of
      flight GISANS allows the tailoring of contrast conditions and thereby the probing
      of more complex morphologies. In addition, recent progress in software packages,
      useful for data analysis for advanced grazing-incidence techniques, is discussed.

PMID- 25610633
TI  - Precession electron diffraction - a topical review.
AB  - In the 20 years since precession electron diffraction (PED) was introduced, it
      has grown from a little-known niche technique to one that is seen as a
      cornerstone of electron crystallography. It is now used primarily in two ways.
      The first is to determine crystal structures, to identify lattice parameters and
      symmetry, and ultimately to solve the atomic structure ab initio. The second is,
      through connection with the microscope scanning system, to map the local
      orientation of the specimen to investigate crystal texture, rotation and strain
      at the nanometre scale. This topical review brings the reader up to date,
      highlighting recent successes using PED and providing some pointers to the future
      in terms of method development and how the technique can meet some of the needs
      of the X-ray crystallography community. Complementary electron techniques are
      also discussed, together with how a synergy of methods may provide the best
      approach to electron-based structure analysis. 

PMID- 25610634
TI  - Superspace crystallography: a key to the chemistry and properties.
AB  - An overview is given of the recent advances in the field of modulated molecular
      and inorganic crystals with an emphasis on the links between incommensurability,
      intermolecular and interatomic interactions and, wherever possible, the
      properties of the materials. The importance of detailed knowledge on the
      modulated structure for understanding the crystal chemistry and the functional
      properties of modulated phases is shown using selected examples of incommensurate
      modulations in organic molecular compounds and inorganic complex oxides. 

PMID- 25610635
TI  - Effectiveness of biostimulation through nutrient content on the bioremediation of
      phenanthrene contaminated soil.
AB  - Bioremediation has shown its applicability for removal of polycyclic aromatic
      hydrocarbons (PAHs) from soil and sediments. In the present study, the effect of
      biostimulation on phenanthrene removal from contaminated soil via adding macro
      and/or micronutrients and trace elements was investigated. For these purposes
      three macro nutrients (as N, P and K), eight micronutrients (as Mg, S, Fe, Cl,
      Zn, Mn, Cu and Na) and four trace elements (as B, Mo, Co and Ni) in 11 mineral
      salts (MS) as variables were used. Placket-Burman statistical design was used to
      evaluate significance of variables (MS) in two levels of high and low. A
      consortium of adapted microorganisms with PAHs was used for inoculation to the
      soil slurry which was spiked with phenanthrene in concentration of 500 mg/kg
      soil. The optimal reduction resulted when a high level of macro nutrient in the
      range of 67-87% and low level of micro nutrient in the range of 12-32% were used
      with the nitrogen as the dominant macronutrient. The Pareto chart showed that
      NH4NO3 was the most effective variable in this experiment. The effect of elements
      on phenanthrene biodegradation showed following sequence as N > K > P > Cl > Na >
      Mg. Effectiveness of the other elements in all runs was less than 1%. The type
      and concentration of nutrient can play an important role in biodegradation of
      phenanthrene. Biostimulation with suitable combination of nutrient can enhance
      bioremediation of PAHs contaminated soils. 

PMID- 25610636
TI  - Purification and Characterization of a Unique Pectin Lyase from Aspergillus
      giganteus Able to Release Unsaturated Monogalacturonate during Pectin
      Degradation.
AB  - A pectin lyase, named PLIII, was purified to homogeneity from the culture
      filtrate of Aspergillus giganteus grown in submerged culture containing orange
      peel waste as carbon source. PLIII was able to digest apple pectin and citrus
      pectins with different degrees of methyl esterification. Interestingly, the PLIII
      activity was stimulated in the presence of some divalent cations including Pb(2+)
      and was not significantly affected by Hg(2+). Like other pectin lyases, PLIII is
      stimulated by but is not dependent on Ca(2+). The main soluble product released
      during the degradation of pectic substances promoted by the PLIII is compatible
      with an unsaturated monogalacturonate. PLIII is a unique enzyme able to release
      unsaturated monogalacturonate as the only soluble product during the degradation
      of pectic substances; therefore, PLIII was classified as an exo-pectin lyase. To
      our knowledge, this is the first characterization of an exo-pectin lyase. The
      PLIII described in this work is potentially useful for ethanol production from
      pectin-rich biomass, besides other common applications for alkaline pectinases
      like preparation of textile fibers, coffee and tea fermentation, vegetable oil
      extraction, and the treatment of pulp in papermaking. 

PMID- 25610637
TI  - Purification and characterization of glucose-6-phosphate dehydrogenase from camel
      liver.
AB  - Glucose-6-phosphate dehydrogenase from camel liver was purified to homogeneity by
      ammonium sulfate precipitation and a combination of DEAE-cellulose, Sephacryl S
      300 gel filtration, and 2', 5' ADP Sepharose 4B affinity chromatography columns.
      The specific activity of camel liver G6PD is increased to 1.80438 units/mg
      proteins with 63-fold purification. It turned out to be homogenous on both native
      PAGE and 12% SDS PAGE, with a molecular weight of 64 kDa. The molecular weight of
      the native form of camel liver G6PD was determined to be 194 kDa by gel
      filtration indicating a trimeric protein. The K m value was found to be 0.081 mM
      of NADP(+). Camel liver G6PD displayed its optimum activity at pH 7.8 with an
      isoelectric point (pI) of pH 6.6-6.8. The divalent cations MgCl2, MnCl2, and
      CoCl2 act as activators; on the other hand, CaCl2 and NiCl2 act as moderate
      inhibitors, while FeCl2, CuCl2, and ZnCl2 are potent inhibitors of camel liver
      G6PD activity. NADPH inhibited camel liver G6PD competitively with K i value of
      0.035 mM. One binding site was deduced for NADPH on the enzyme molecule. This
      study presents a simple and reproducible purification procedure of G6PD from the
      camel liver. 

PMID- 25610638
TI  - Environmental triggers and autoimmunity.

PMID- 25610639
TI  - Avoiding weight gain in cardiometabolic disease: a systematic review.
AB  - Patients with cardiometabolic disease are at higher risk for obesity-related
      adverse effects. Even without weight loss, weight maintenance may be beneficial.
      We performed a systematic review to identify the effect of nonweight loss-focused
      lifestyle interventions in adults with cardiometabolic disease. We searched
      MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to
      identify comparative studies of lifestyle interventions (self-management, diet,
      exercise, or their combination) without a weight loss focus in adults with or at
      risk for diabetes and cardiovascular disease. Weight, BMI, and waist
      circumference at >=12 months were the primary outcomes. Of 24,870 citations, we
      included 12 trials (self-management, n = 2; diet, n = 2; exercise, n = 2;
      combination, n = 6) studying 4,206 participants. Self-management plus physical
      activity +/- diet versus minimal/no intervention avoided meaningful weight (-0.65
      to -1.3 kg) and BMI (-0.4 to -0.7 kg/m(2)) increases. Self-management and/or
      physical activity prevented meaningful waist circumference increases versus
      control (-2 to -4 cm). In patients with cardiometabolic disease, self-management
      plus exercise may prevent weight and BMI increases and self-management and/or
      exercise may prevent waist circumference increases versus minimal/no
      intervention. Future studies should confirm these findings and evaluate
      additional risk factors and clinical outcomes. 

PMID- 25610641
TI  - Determinants of Antiretroviral Therapy Adherence among Women in Southern Malawi:
      Healthcare Providers' Perspectives.
AB  - Background. The purpose of this study was to explore healthcare providers'
      perspectives on antiretroviral (ART) adherence in two ART clinics in southern
      Malawi. Nonadherence to ART is a significant hindrance to the success of HIV/AIDS
      treatment. Methods. A one-on-one semistructured interview was conducted with
      eight healthcare providers in two ART clinics in rural and urban southern Malawi.
      The interviews were focused on factors facilitating or hindering ART adherence
      and strategies to improve adherence. Interviews were audio-recorded, transcribed,
      and content-analyzed with the use of the constant comparison approach. Results.
      Of the eight participants, 63% were between the ages of 20 and 30 years and 37%
      were HIV counselors. Factors facilitating adherence include patients' belief and
      knowledge, HIV/AIDS education, and a supportive network. Barriers to adherence
      include discrimination, nondisclosure of HIV status, food insecurity, medication
      side effects, religion, misinformation, and staff and drug shortages. Strategies
      to improve adherence were identified by participants to include nutritional/food
      supplementation for malnourished or undernourished patients and patient
      counseling. Conclusions. There is a need for collaborative efforts between
      healthcare providers, patients, and faith-based organizations to identify and
      address hindrances and facilitators to patients' adherence. Further research is
      needed to develop strategies addressing religion, staff, and drug shortages. 

PMID- 25610640
TI  - Identification of novel clinical factors associated with hepatic fat accumulation
      in extreme obesity.
AB  - OBJECTIVES: The accumulation of lipids stored as excess triglycerides in the
      liver (steatosis) is highly prevalent in obesity and has been associated with
      several clinical characteristics, but most studies have been based on relatively
      small sample sizes using a limited set of variables. We sought to identify
      clinical factors associated with liver fat accumulation in a large cohort of
      patients with extreme obesity. METHODS: We analyzed 2929 patients undergoing
      intraoperative liver biopsy during a primary bariatric surgery. Univariate and
      multivariate regression modeling was used to identify associations with over 200
      clinical variables with the presence of any fat in the liver and with moderate to
      severe versus mild fat accumulation. RESULTS: A total of 19 data elements were
      associated with the presence of liver fat and 11 with severity of liver fat
      including ALT and AST, plasma lipid, glucose, and iron metabolism variables,
      several medications and laboratory measures, and sleep apnea. The accuracy of a
      multiple logistic regression model for presence of liver fat was 81% and for
      severity of liver fat accumulation was 77%. CONCLUSIONS: A limited set of
      clinical factors can be used to model hepatic fat accumulation with moderate
      accuracy and may provide potential mechanistic insights in the setting of extreme
      obesity.

PMID- 25610642
TI  - Advances in medical revascularisation treatments in acute ischemic stroke.
AB  - Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and
      there has been ongoing research to find a drug that can promote vessel
      recanalisation more completely and with less side effects. In this review
      article, the major studies which have validated the use and safety of tPA are
      discussed. The safety and efficacy of other thrombolytic and anticoagulative
      agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab,
      eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are
      both plasminogen activators with higher fibrin affinity and longer half-life
      compared to alteplase. They have shown greater reperfusion rates and improved
      functional outcomes in preliminary studies. Argatroban is a direct thrombin
      inhibitor used as an adjunct to intravenous tPA and showed higher rates of
      complete recanalisation in the ARTTS study with further studies which are now
      ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also
      being investigated and have shown higher rates of complete recanalisation, for
      example, in the CLOTBUST study. Overall, development in medical therapies for
      stroke is important due to the ease of administration compared to endovascular
      treatments, and the new treatments such as tenecteplase, desmoteplase, and
      adjuvant sonothrombolysis are showing promising results and await further large
      scale clinical trials. 

PMID- 25610643
TI  - Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a
      Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors.
AB  - For imaging of dopamine D2/3 receptors, agonist tracers are favoured over
      antagonists because they are more sensitive to detection of dopamine release and
      because they may selectively label the high-affinity receptor state. We have
      developed novel D2/3 receptor selective agonists that can be radiolabelled with
      [(123)I], which label is advantageous over most other labels, such as carbon-11,
      as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman
      2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for
      development as it shows high binding affinity to D2/3 receptors in vitro, and
      here we report on the characterization of this first [(123)I]-labelled D2/3
      receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate
      tin precursor for [(123)I]-1 was developed and was successfully radiolabelled
      with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for
      [(123)I]-1. In biodistribution experiments in Wistar rats intravenous injection
      of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the
      D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30
      min to 4 h p.i. Storage phosphor imaging experiments, however, did not show
      specific D2/3 receptor binding. In conclusion, despite promising in vitro data
      for 1, neither specific ex vivo binding nor high signal-to-noise ratios were
      found in rodents for [(123)I]-1. 

PMID- 25610644
TI  - Desmopressin acetate in intracranial haemorrhage.
AB  - Introduction. The secondary increase in the size of intracranial haematomas as a
      result of spontaneous haemorrhage or trauma is of particular relevance in the
      event of prior intake of platelet aggregation inhibitors. We describe the effect
      of desmopressin acetate as a means of temporarily stabilising the platelet
      function. Patients and Methods. The platelet function was analysed in 10 patients
      who had received single (N = 4) or multiple (N = 6) doses of acetylsalicylic acid
      and 3 patients (control group) who had not taken acetylsalicylic acid. All
      subjects had suffered intracranial haemorrhage. Analysis was performed before,
      half an hour and three hours after administration of desmopressin acetate.
      Statistical analysis was performed by applying a level of significance of P <=
      0.05. Results. (1) Platelet function returned to normal 30 minutes after
      administration of desmopressin acetate. (2) The platelet function worsened again
      after three hours. (3) There were no complications related to electrolytes or
      fluid balance. Conclusion. Desmopressin acetate can stabilise the platelet
      function in neurosurgical patients who have received acetylsalicylic acid prior
      to surgery without causing transfusion-related side effects or a loss of time.
      The effect is, however, limited and influenced by the frequency of drug intake.
      Further controls are needed in neurosurgical patients. 

PMID- 25610645
TI  - Evaluation of 11 scoring functions performance on matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) have distinctive roles in various physiological
      and pathological processes such as inflammatory diseases and cancer. This study
      explored the performance of eleven scoring functions (D-Score, G-Score,
      ChemScore, F-Score, PMF-Score, PoseScore, RankScore, DSX, and X-Score and scoring
      functions of AutoDock4.1 and AutoDockVina). Their performance was judged by
      calculation of their correlations to experimental binding affinities of 3D ligand
      enzyme complexes of MMP family. Furthermore, they were evaluated for their
      ability in reranking virtual screening study results performed on a member of MMP
      family (MMP-12). Enrichment factor at different levels and receiver operating
      characteristics (ROC) curves were used to assess their performance. Finally, we
      have developed a PCA model from the best functions. Of the scoring functions
      evaluated, F-Score, DSX, and ChemScore were the best overall performers in
      prediction of MMPs-inhibitors binding affinities while ChemScore, Autodock, and
      DSX had the best discriminative power in virtual screening against the MMP-12
      target. Consensus scorings did not show statistically significant superiority
      over the other scorings methods in correlation study while PCA model which
      consists of ChemScore, Autodock, and DSX improved overall enrichment. Outcome of
      this study could be useful for the setting up of a suitable scoring protocol,
      resulting in enrichment of MMPs inhibitors. 

PMID- 25610646
TI  - Synthesis and structural activity relationship study of antitubercular
      carboxamides.
AB  - The unusual structure and chemical composition of the mycobacterial cell wall,
      the tedious duration of therapy, and resistance developed by the microorganism
      have made the recurrence of the disease multidrug resistance and extensive or
      extreme drug resistance. The prevalence of tuberculosis in synergy with HIV/AIDS
      epidemic augments the risk of developing the disease by 100-fold. The need to
      synthesize new drugs that will shorten the total duration of effective treatment
      and/or significantly reduce the dosage taken under DOTS supervision, improve on
      the treatment of multidrug-resistant tuberculosis which defies the treatment with
      isoniazid and rifampicin, and provide effective treatment for latent TB
      infections which is essential for eliminating tuberculosis prompted this review.
      In this review, we considered the synthesis and structure activity relationship
      study of carboxamide derivatives with antitubercular potential. 

PMID- 25610647
TI  - Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the
      Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella
      pneumoniae.
AB  - Circular dichroism and (1)H NMR were used to investigate the interactions of a
      series of synthetic antimicrobial peptides (AMPs) with lipopolysaccharides (LPS)
      isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae. Previous CD
      studies with AMPs containing only three Tic-Oic dipeptide units do not exhibit
      helical characteristics upon interacting with small unilamellar vesicles (SUVs)
      consisting of LPS. Increasing the number of Tic-Oic dipeptide units to six
      resulted in five analogues with CD spectra that exhibited helical characteristics
      on binding to LPS SUVs. Spectroscopic and in vitro inhibitory data suggest that
      there are two possible helical conformations resulting from two different AMP-LPS
      binding mechanisms. Mechanism one involves a helical binding conformation where
      the AMP binds LPS very strongly and is not efficiently transported across the LPS
      bilayer resulting in the loss of inhibitory activity. Mechanism two involves a
      helical binding conformation where the AMP binds LPS very loosely and is
      efficiently transported across the LPS bilayer resulting in an increase in
      inhibitory activity. Mechanism three involves a nonhelical binding conformation
      where the AMP binds LPS very loosely and is efficiently transported across the
      LPS bilayer resulting in an increase in inhibitory activity. 

PMID- 25610648
TI  - Electron microscopy in rat brain slices reveals rapid accumulation of Cisplatin
      on ribosomes and other cellular components only in glia.
AB  - Cisplatin is a widely used, effective anticancer drug. Its use, however, is
      associated with several side effects including nephrotoxicity and neurotoxicity.
      It is known that cisplatin is accumulated in cells by the organic cation
      transport system and reacts with nucleotides, damaging them, but the precise
      target of cisplatin-induced neurotoxicity remains obscure. Here we report direct
      visualization of cisplatin inside brain cells using in vivo "cisplatin staining,"
      a technique that takes advantage of the high electron density of cisplatin, which
      contains platinum (atomic mass = 195). After applying 0.1% cisplatin to living
      brain slices for 30 min, we fixed the tissue and observed the accumulated
      cisplatin using electron microscopy. We found that cisplatin was localized mainly
      to ribosomes associated with endoplasmic reticulum (EPR) in glial cells and to
      the myelin sheath formed by oligodendrocytes around neuronal axons. Staining of
      nuclear DNA was moderate. Our in vivo "cisplatin staining" method validated that
      the main target of cisplatin is a direct attack on myelin and the RNA contained
      in ribosomes. 

PMID- 25610650
TI  - Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis
      via Induction of Neurogenesis and Oligodendrogenesis.
AB  - Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple
      sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However,
      the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth
      factor (EGF) stimulates NSC proliferation and mobilization to demyelinated
      lesions but also induces astrogenesis and glial scar. Objective. To examine the
      clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE
      induced SJL mice were intravenously treated with either anti-EGF neutralizing
      antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of
      each group were daily treated for 9 days with BrdU and then sacrificed for
      immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly
      ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift
      from BrdU(+)GFAP(+) NSCs to BrdU(+)DCX(+) neuroblasts in the subventricular zone
      (SVZ), increased BrdU(+)NeuN(+) neurons in the granular cell layer of the dentate
      gyrus, and increased BrdU(+)O4(+) oligodendrocytes in the SVZ. There was no
      change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions.
      Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and
      oligodendrogenesis. No immunosuppressive effect was found. Further investigation
      is needed to support these notions of beneficial effect of anti-EGF Ab in MS. 

PMID- 25610651
TI  - The quality assessment of stored red blood cells probed using atomic-force
      microscopy.
AB  - At the moment the suitability of stored red blood cells (sRBC) for transfusion is
      checked by routine methods such as haemoglobin estimation and the level of
      haemolysis. These methods cannot characterize directly the quality of the
      membranes of sRBC. The aim of this work is to assess the quality of sRBC based on
      such criteria as the membrane's stiffness and the size and the form of sRBC.
      Materials and Methods. We have investigated 5 series of dry cytosmears of the
      sRBC which had been kept in blood bank in a period from 1 to 35 days. After AFM
      imaging, in every specimen, 5 RBC were chosen at random; the diameter, the
      height, and the stiffness were measured on each of them. Results. The present
      study shows high increase of the mean values of YM and height of RBC after 35
      days of storage and decrease of the mean values of their diameter. Conclusion.
      Statistically significant high increase of the mean values of YM indicates the
      decrease of the elasticity of the cells in the course of storing of the RBC. This
      parameter along with the morphological characteristics can be used as criterion
      for assessment of applicability of the sRBC for blood transfusion. 

PMID- 25610652
TI  - Game Analysis, Validation, and Potential Application of EyeToy Play and Play 2 to
      Upper-Extremity Rehabilitation.
AB  - Objective. To describe and analyze the potential use of games in the commercially
      available EyeToy Play and EyeToy Play 2 on required/targeted training skills and
      feedback provided for clinical application. Methods. A summary table including
      all games was created. Two movement experts naive to the software validated
      required/targeted training skills and feedback for 10 randomly selected games.
      Ten healthy school-aged children played to further validate the required/targeted
      training skills. Results. All but two (muscular and cardiovascular endurance) had
      excellent agreement in required/targeted training skills, and there was 100%
      agreement on feedback. Children's performance in required/targeted training
      skills (number of unilateral reaches and bilateral reaches, speed, muscular
      endurance, and cardiovascular endurance) significantly differed between games (P
      < .05). Conclusion. EyeToy Play games could be used to train children's arm
      function. However, a careful evaluation of the games is needed since performance
      might not be consistent between players and therapists' interpretation. 

PMID- 25610649
TI  - Efficacy of female rat models in translational cardiovascular aging research.
AB  - Cardiovascular disease is the leading cause of death in women in the United
      States. Aging is a primary risk factor for the development of cardiovascular
      disease as well as cardiovascular-related morbidity and mortality. Aging is a
      universal process that all humans undergo; however, research in aging is limited
      by cost and time constraints. Therefore, most research in aging has been done in
      primates and rodents; however it is unknown how well the effects of aging in rat
      models translate into humans. To compound the complication of aging gender has
      also been indicated as a risk factor for various cardiovascular diseases. This
      review addresses the systemic pathophysiology of the cardiovascular system
      associated with aging and gender for aging research with regard to the
      applicability of rat derived data for translational application to human aging. 

PMID- 25610654
TI  - Fatty Acid composition and levels of selected polyunsaturated Fatty acids in four
      commercial important freshwater fish species from lake victoria, Tanzania.
AB  - Fatty acids (FAs) particularly omega3 and omega6 polyunsaturated fatty acids
      (PUFAs) play important role in human health. This study aimed to investigate the
      composition and levels of selected omega3 PUFAs in four commercial fish species,
      Nile perch (Lates niloticus), Nile tilapia (Oreochromis niloticus), Tilapia
      zillii, and dagaa (Rastrineobola argentea) from Mwanza Gulf in Lake Victoria. The
      results indicated that 36 types of FAs with different saturation levels were
      detected. These FAs were dominated by docosahexaenoic (DHA), eicosapentaenoic
      (EPA), docosapentaenoic (DPA), and eicosatetraenoic acids. O. niloticus had the
      highest composition of FAs (34) compared to L. niloticus (27), T. zillii (26),
      and R. argentea (21). The levels of EPA differed significantly among the four
      commercial fish species (F = 6.19,  P = 0.001). The highest EPA levels were found
      in R. argentea followed by L. niloticus and O. niloticus and the lowest in T.
      zillii. The DPA levels showed no significant difference among the four fish
      species studied (F = 0.652,  P = 0.583). The study concluded that all four
      commercial species collected from Mwanza Gulf are good for human health, but R.
      argentea is the best for consumption because it contains higher levels of omega3
      FAs, mainly EPA. 

PMID- 25610653
TI  - Selective Migration of Subpopulations of Bone Marrow Cells along an SDF-1alpha
      and ATP Gradient.
AB  - Both stem cell chemokine stromal cell-derived factor-1alpha (SDF-1alpha) and
      extracellular nucleotides such as adenosine triphosphate (ATP) are increased in
      ischemic myocardium. Since ATP has been reported to influence cell migration, we
      analysed the migratory response of bone marrow cells towards a combination of SDF
      1 and ATP. Total nucleated cells (BM-TNCs) were isolated from bone marrow of
      cardiac surgery patients. Migration assays were performed in vitro. Subsequently,
      migrated cells were subjected to multicolor flow cytometric analysis of CD133,
      CD34, CD117, CD184, CD309, and CD14 expression. BM-TNCs migrated significantly
      towards a combination of SDF-1 and ATP. The proportions of CD34+ cells as well as
      subpopulations coexpressing multiple stem cell markers were selectively enhanced
      after migration towards SDF-1 or SDF-1 + ATP. After spontaneous migration,
      significantly fewer stem cells and CD184+ cells were detected. Direct incubation
      with SDF-1 led to a reduction of CD184+ but not stem cell marker-positive cells,
      while incubation with ATP significantly increased CD14+ percentage. In summary,
      we found that while a combination of SDF-1 and ATP elicited strong migration of
      BM-TNCs in vitro, only SDF-1 was responsible for selective attraction of
      hematopoietic stem cells. Meanwhile, spontaneous migration of stem cells was
      lower compared to BM-TNCs or monocytes. 

PMID- 25610655
TI  - A Metabonomic Study of the Effect of Methanol Extract of Ginger on Raji Cells
      Using (1)HNMR Spectroscopy.
AB  - Cancer is currently a major international health problem. The development of
      resistance to chemotherapy has resulted in the search for herbal drugs. Ginger is
      a medicinal plant with several clinical applications. Metabolomics is a
      simultaneous detection of all the metabolites by use of (1)HNMR or mass
      spectroscopy and interpretation by modeling software. The purpose of this study
      was to detect the altered metabolites of Raji cells in the presence of ginger
      extract in vitro. Cells were cultured in the presence and absence of methanolic
      ginger extract in RPMI medium. IC50 determined by MTT and lipophilic and
      hydrophilic extracts were prepared from control and treated groups which were
      analyzed by (1)HNMR. The IC50 was 1000 MUg/mL. Modeling of spectra was carried
      out on the two groups using OSC-PLS with MATLAB software and the main metabolites
      detected. Further analysis was carried out using MetaboAnalyst database. The main
      metabolic pathways affected by the ginger extract were detected. Ginger extract
      was seen to effect the protein biosynthesis, amino acid, and carbohydrate
      metabolism and had a strong cytotoxic effect on Raji cells in vitro. 

PMID- 25610656
TI  - Enhanced Production of Ligninolytic Enzymes by a Mushroom Stereum ostrea.
AB  - The white rot fungi Stereum ostrea displayed a wide diversity in their response
      to supplemented inducers, surfactants, and copper sulphate in solid state
      fermentation. Among the inducers tested, 0.02% veratryl alcohol increased the
      ligninolytic enzyme production to a significant extent. The addition of copper
      sulphate at 300 MUM concentration has a positive effect on laccase production
      increasing its activity by 2 times compared to control. Among the surfactants,
      Tween 20, Tween 80, and Triton X 100, tested in the studies, Tween 80 stimulated
      the production of ligninolytic enzymes. Biosorption of dyes was carried out by
      using two lignocellulosic wastes, rice bran and wheat bran, in 50 ppm of remazol
      brilliant blue and remazol brilliant violet 5R dyes. These dye adsorbed
      lignocelluloses were then utilized for the production of ligninolytic enzymes in
      solid state mode. The two dye adsorbed lignocelluloses enhanced the production of
      laccase and manganese peroxidase but not lignin peroxidase. 

PMID- 25610657
TI  - Outcomes and complications of the midline anterior approach 3 years after lumbar
      spine surgery.
AB  - Objective. The purpose of this study was to evaluate a new questionnaire to
      assess outcomes related to the midline anterior lumbar approach and to identify
      risk factors for negative patient responses. Methods. A retrospective review of
      58 patients who underwent anterior lumbar surgery at a single institution for
      either degenerative disc disease or spondylolisthesis in 2009 was performed. The
      outcome measures included our newly developed Anterior Lumbar Surgery
      Questionnaire (ALSQ), ODI, and EQ-5D. Results. There were 58 patients available
      for followup, 27 women and 31 men. The average age at surgery was 50.8 years,
      with an average followup of 2.92 years. The average change in ODI was 34.94
      (22.7) and EQ-5D was 0.28 (0.29). The rate of complications with the anterior
      approach was 10.3% and there was one male patient (3.2%) with retrograde
      ejaculation. Determination of the effectiveness of the new ALSQ revealed that it
      significantly correlated to the EQ-5D and ODI (P < 0.05). Smoking was associated
      with a negative response on thirteen questions. BMP use was not associated with a
      negative response on any sexual function questions. Conclusions. Our new Anterior
      Lumbar Surgery Questionnaire determines patient perceived complications related
      to the midline anterior lumbar surgical approach. 

PMID- 25610658
TI  - Determination of the Maximal Corrective Ability and Optimal Placement of the
      Ortho-SUV Frame for Femoral Deformity with respect to the Soft Tissue Envelope, a
      Biomechanical Modelling Study.
AB  - Circular fixation according to the Ilizarov method is a well-recognised modality
      of treatment for trauma and deformity. One shortcoming of the traditional fixator
      is its limited ability to correct more than one plane of deformity
      simultaneously, leading to lengthy frame-time indices. Hexapod circular fixation
      utilising computer guidance is commonplace for complex multidimensional deformity
      but difficulties often arise with correction of femoral deformity due to
      bulkiness of the frame construct, particularly in proximal deformity and in
      patients of increased size. The Ortho-SUV frame is an innovative hexapod which
      permits unique customisation to individual patient anatomy to maximise tolerance
      and optimal range of deformity correction. We hypothesised that the optimal
      configuration and maximal degree of correction achievable by the Ortho-SUV frame
      can be biomechanically modelled and applied clinically. A study was constructed
      using Ortho-SUV and femoral limb models to measure deformity correction via
      differing frame constructs and determine optimal frame configuration to achieve
      correction in proximal, middle, and distal third deformities with respect to the
      soft tissue envelope. The ideal frame configuration is determined for correction
      of deformity in all locations of the femur with the maximal parameters of
      correction calculated whilst avoiding and mitigating soft tissue irritation from
      bulky frame construction. 

PMID- 25610659
TI  - The reliability of classifications of proximal femoral fractures with 3
      dimensional computed tomography: the new concept of comprehensive classification.
AB  - The reliability of proximal femoral fracture classifications using 3DCT was
      evaluated, and a comprehensive "area classification" was developed. Eleven
      orthopedists (5-26 years from graduation) classified 27 proximal femoral
      fractures at one hospital from June 2013 to July 2014 based on preoperative
      images. Various classifications were compared to "area classification." In "area
      classification," the proximal femur is divided into 4 areas with 3 boundary
      lines: Line-1 is the center of the neck, Line-2 is the border between the neck
      and the trochanteric zone, and Line-3 links the inferior borders of the greater
      and lesser trochanters. A fracture only in the first area was classified as a
      pure first area fracture; one in the first and second area was classified as a 1
      2 type fracture. In the same way, fractures were classified as pure 2, 3-4, 1-2
      3, and so on. "Area classification" reliability was highest when orthopedists
      with varying experience classified proximal femoral fractures using 3DCT. Other
      classifications cannot classify proximal femoral fractures if they exceed each
      classification's particular zones. However, fractures that exceed the target
      zones are "dangerous" fractures. "Area classification" can classify such
      fractures, and it is therefore useful for selecting osteosynthesis methods. 

PMID- 25610660
TI  - Two-Stage Revision TKA Is Associated with High Complication and Failure Rates.
AB  - Despite two-stage revision remaining the gold standard in treating periprosthetic
      infection of total knee arthroplasty (TKA), there remains uncertainty regarding
      the actual success rate and the risk factors for failure. We retrospectively
      reviewed 58 knees with mean follow-up of 38 months who underwent two-stage
      revision TKAs from 1998 to 2012 by a single surgeon. Failure was defined as
      persistent infection or reoperation after two-stage revision TKA surgery. Failure
      occurred in 36%. The overall mortality was 22%. The mean time to reinfection was
      26 months. Polymicrobial infection was associated with a higher risk of failure
      (RR 3.31, P < 0.001). Knees requiring soft tissue coverage were also at a greater
      risk of failure (RR 2.67, P = 0.001), as were knees that underwent four or more
      additional surgeries after the primary TKA and prior to stage-one explantation
      (RR 2.25, P = 0.020). Thus, opportunities exist for improvement in management of
      infected TKA. 

PMID- 25610661
TI  - Congenital microstomia in a neonate with impending respiratory compromise.
AB  - Microstomia is the term used to describe a reduction in the size of the oral
      aperture that is severe enough to compromise quality of life, nutrition, and
      cosmesis. Few cases of congenital microstomia have been reported as most
      microstomia cases are due to burn injuries. We are presenting a case of a neonate
      who was found to be in respiratory distress with severe congenital microstomia
      from no known cause. This case illustrates the rarity of this type of pathologic
      anatomy as well as the teamwork and tools necessary to treat these patients. 

PMID- 25610662
TI  - Entanglement due to Delayed Removal of a Buddy Wire.
AB  - A buddy wire is often used to aid in the delivery of balloons and stents when
      negotiating tortuous or calcified vessels. We present a planned two-stent mini
      crush intervention complicated by entanglement of the buddy wire with the second
      stent and subsequent distortion of the stent within the guiding catheter. Based
      on this case, we suggest removing the buddy wire immediately after successful
      positioning of the first stent, because entrapment with a second stent is
      possible and may lead to challenging situations in a simultaneous two-stent
      strategy. 

PMID- 25610663
TI  - Fragment reattachment after atypical crown fracture in maxillary central incisor.
AB  - Background. Fracture by trauma is one of the most common types of dental injury
      in the permanent dentition among children and teenagers. Aim. The aim of this
      study was to report the treatment performed to an atypical dental trauma case in
      a maxillary central incisor of a young patient by means of reattachment of the
      tooth fragment. Case Description. A 12-year-old male patient suffered a vertical
      crown fracture to the maxillary right central incisor. After clinical and
      radiographic examinations, a conservative restorative treatment which consisted
      in the reattachment of the tooth fragment with flow resin was performed in order
      to preserve the dental element and to obtain maximum aesthetics. Conclusion. The
      reattachment of fractured fragment is a fast and easy technique that can be used
      successfully as an option to restore dental element which suffered trauma.
      Clinical Significance. This technique restores the aesthetics and function of the
      dental element with minimal discomfort to the patient. 

PMID- 25610664
TI  - Severe Hyponatremia due to Phlegmonous Trismus.
AB  - We describe a patient with dysphagia and trismus associated with lower jaw
      inflammation due to phlegmon who developed severe hyponatremia from water
      intoxication due to excessive water intake after diaphoresis caused by abnormally
      hot weather. A 63-year-old woman presented with severe swelling of the floor of
      the mouth and trismus. As she had spasms and numbness of the extremities and
      restlessness and water intoxication caused by excessive water intake was
      suspected, she was hospitalized for the treatment of inflammation and electrolyte
      disorder. Although swelling of the floor of the mouth subsided over time after
      antimicrobial therapy, vomiting, diarrhea, and numbness of the extremities
      continued. On day 5 of hospitalization, severe vomiting and diarrhea recurred,
      and serum sodium levels decreased to 108 mEq/L. Decrease in water intake is
      essential in the treatment of hyponatremia. However, in patients with severe
      vomiting and diarrhea who can swallow only liquids because of hot weather and
      eating disorder, the risk of sodium depletion is high. It is important to restore
      electrolyte balance and fluid volume through supplementation with sodium,
      chlorine, potassium, and glucose among others, the reduction of intravenous fluid
      volume, and diuresis in order to correct the sodium level slowly. 

PMID- 25610665
TI  - Digital device in postextraction implantology: a clinical case presentation.
AB  - Aim. The aim of this work is to describe a case of immediate implant placement
      after extraction of the upper right first premolar, with the use of CAD/CAM
      technology, which allows an early digital impression of the implant site with an
      intraoral scanner (MHT 3D Progress, Verona, Italy). Case Report. A 46-year-old
      female was referred with a disorder caused by continuous debonding of the
      prosthetic crown on the upper right first premolar. Clinically, there were no
      signs, and the evaluation of the periapical radiograph showed a fracture of the
      root, with a mesial well-defined lesion of the hard tissue of the upper right
      first premolar, as the radiolucent area affected the root surface of the tooth.
      It was decided, in accordance with the patient, that the tooth would be extracted
      and the implant (Primer, Edierre implant system, Genoa, Italy) with diameter of
      4.2 mm and length of 13 mm would be inserted. After the insertion of the implant,
      it was screwed to the scan abutment, and a scan was taken using an intraoral
      scanner (MHT 3D Progress, Verona, Italy). The scanned images were processed with
      CAD/CAM software (Exocad DentalCAD, Darmstadt, Germany) and the temporary crown
      was digitally drawn (Dental Knowledge, Milan, Italy) and then sent to the milling
      machine for production with a composite monoblock. After 4 months, when the
      implant was osteointegrated, it was not necessary to take another dental
      impression, and the definitive crown could be screwed in. Conclusion. The CAD/CAM
      technology is especially helpful in postextraction implant for aesthetic
      rehabilitation, as it is possible to immediately fix a provisional crown with an
      anatomic shape that allows an optimal healing process of the tissues. Moreover,
      the removal of healing abutments, and the use of impression copings, impression
      materials, and dental stone became unnecessary, enabling the reduction of the
      chair time, component cost, and patient's discomfort. However, it is still
      necessary for scientific research to continue to carry out studies on this
      procedure, in order to improve the accuracy, the reliability, and the
      reproducibility of the results. 

PMID- 25610666
TI  - Oral and dental findings of dyskeratosis congenita.
AB  - Dyskeratosis congenital (DC) is a rare condition characterized by reticulate skin
      hyperpigmentation, mucosal leukoplakia, and nail dystrophy. More serious features
      are bone marrow involvement with pancytopenia and a predisposition to malignancy.
      The purpose of this case report is to describe the oral and dental findings in
      children with DC syndrome. A 10-year-old male diagnosed with DC was admitted
      because of extensive caries and toothache. Inadequate oral hygiene and extensive
      caries were observed in oral examination of the patient. Plaque accumulation was
      seen in gingival border of maxillary teeth. Papillary atrophy on the tongue was
      observed. Short and blunted roots of mandible incisors and upper and lower molars
      were determined on the radiographic examination. Dryness on the lips and
      commisuras, ectropion on his eyes, and epiphora were observed. Hematologic tests
      were performed and showed aplastic anemia at the age of 2. At the age of 4, the
      bone marrow transplantation was performed. Dermatological findings occurred after
      the bone marrow transplantation. The skin of the patient was thin, dry, and
      wrinkled in some areas. He had palmoplantar hyperkeratosis and syndactylia on his
      fingers. Endodontic treatment procedures were applied and other extensive caries
      are still being restored. The patient will be given full preventive care during
      regular follow-up. Oral hygiene was improved to the optimum level. 

PMID- 25610667
TI  - Maxillary chronic osteomyelitis caused by domestic violence: a diagnostic
      challenge.
AB  - Maxillary osteomyelitis is a rare condition defined as inflammation of the bone
      primarily caused by odontogenic bacteria, with trauma being the second leading
      cause. The present report documents a rare case of maxillary osteomyelitis in a
      38-year-old female who was the victim of domestic violence approximately a year
      prior to presentation. Intraoral examination revealed a lesion appearing as
      exposed bony sequestrum, with significant destruction of gingiva and alveolar
      mucosa in the maxillary right quadrant, accompanied by significant pain, local
      edema, and continued purulence. Teeth numbers 11, 12, 13, 14, and 15 were mobile,
      not responsive to percussion, and nonvital. Treatment included antibiotic therapy
      for seven days followed by total enucleation of the necrotic bone tissue and
      extraction of the involved teeth. Microscopic findings confirmed the clinical
      diagnosis of chronic suppurative osteomyelitis. Six months postoperatively, the
      treated area presented complete healing and there was no sign of recurrence of
      the lesion. 

PMID- 25610668
TI  - Acquired brachial cutaneous dyschromatosis in a 60-year-old male: a case report
      and review of the literature.
AB  - Acquired brachial cutaneous dyschromatosis is an acquired pigmentary disorder
      that has been described in only 20 patients but likely affects many more. This
      case of a man with acquired brachial cutaneous dyschromatosis is unique as most
      reports are in women. We report the case of a 60-year-old male who presents with
      an asymptomatic eruption characterized by hyperpigmented and telangiectatic
      macules coalescing into patches on the bilateral extensor aspects of the forearms
      which is consistent clinically and histopathologically with acquired brachial
      cutaneous dyschromatosis. Given its presence in patients with clinical evidence
      of chronic sun exposure and its histopathological finding of solar elastosis,
      acquired brachial cutaneous dyschromatosis is likely a disorder caused by
      cumulative UV damage. However, a possible association between angiotensin
      converting enzyme inhibitors and acquired brachial cutaneous dyschromatosis
      exists. Further investigation is needed to elucidate both the pathogenesis of the
      disorder and forms of effective management. Treatment of the disorder should
      begin with current established treatments for disorders of dyspigmentation. 

PMID- 25610669
TI  - Acutely onset amiodarone-induced angioedema in a patient with new atrial
      fibrillation.
AB  - A 50-year-old man was admitted to our emergency department due to new episode of
      palpitation. He had history of angioplasty of right coronary artery (RCA) with
      drug eluting stent 2 years ago. His electrocardiogram revealed atrial
      fibrillation (AF). Intravenous amiodarone 150 mg during 10 minutes and then 1
      mg/min infusion were started to achieve rate control and pharmacologic conversion
      to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed
      swelling of the skin around his mouth and eyes, and also mucosa of the mouth,
      eyes and tongue. To conclude, angioedema should be considered a rare side effect
      of amiodarone which is used broadly in cardiovascular field. 

PMID- 25610670
TI  - Atypical presentation of traumatic aortic injury.
AB  - Background. Blunt thoracic aorta injury (BAI) is second only to head injury as
      cause of mortality in blunt trauma. While most patients do not survive till
      arrival at the hospital, for the remainder, prompt diagnosis and treatment
      greatly improve outcomes. We report an atypical presentation of BAI, highlighting
      the diagnostic challenges of this condition in the emergency department. Case
      Presentation. A previously well 25-year-old male presented 15 hours after injury
      hemodynamically stable with delirium. There were no signs or symptoms suggestive
      of BAI. Sonography showed small bilateral pleural effusions. Chest radiograph
      showed a normal mediastinum. Eventually, CT demonstrated a contained distal
      aortic arch disruption. The patient underwent percutaneous endovascular thoracic
      aortic repair and recovered well. Conclusion. This catastrophic lesion may
      present with few reliable signs and symptoms; hence, a high index of suspicion is
      crucial for early diagnosis and definitive surgical management. This paper
      discusses the diagnostic utility of clinical features, injury mechanism, and
      radiographic modalities. Consideration of mechanism of injury, clinical features,
      and chest radiograph findings should prompt advanced chest imaging. 

PMID- 25610671
TI  - A Case of Primary Hyperparathyroidism due to Intrathyroidal Parathyroid Cyst.
AB  - Parathyroid cysts constitute 0.08-3.41% of all parathyroid masses. Intrathyroidal
      parathyroid cysts, however, are rare conditions with only a few cases being
      reported. Most of the parathyroid cysts are found to be nonfunctional and
      functional cysts are generally thought to be due to cystic degeneration of
      parathyroid adenomas. A cystic, smooth contoured lesion of 24 * 19 * 16 mm was
      observed in left thyroid lobe of a 76-year-old woman during ultrasonography which
      was performed as routine workup for primary hyperparathyroidism. It was defined
      as a cystic thyroid nodule at first. Tc(99m) sestamibi scintigraphy was performed
      to see any parathyroid lesions, but no radioactive uptake was observed. Intact
      parathormone (iPTH) level was found to be >600 pg/mL in cyst aspiration fluid.
      Left lobectomy was performed, with a diagnosis of primary hyperparathyroidism due
      to functional parathyroid cyst. Serum iPTH level was decreased >50%
      postoperatively and histopathological evaluation was consistent with an
      encapsulated parathyroid adenoma with a cystic center. Parathyroid cysts are
      among rare causes of primary hyperparathyroidism. Diagnosis is made by markedly
      increased iPTH level in cyst fluid and observation of parathyroid epithelium
      lining the cyst wall. 

PMID- 25610672
TI  - Acute onset collagenous colitis with unique endoscopic findings.
AB  - We experienced a rare case of 72-year-old woman with acute onset collagenous
      colitis (CC) induced by lansoprazole. The patient developed acute abdominal pain,
      watery diarrhea, and melena that are quite rare in usual CC. We could find the
      characteristic colonoscopic findings such as active long liner ulcers in the
      patient. We also observed the healing courses of these unique findings. Our case
      indicates two important points of view. (1) CC sometimes develops with acute
      onset symptoms which resemble those of ischemic colitis. (2) Colonoscopy would be
      useful and necessary to distinguish acute onset CC and ischemic colitis. 

PMID- 25610673
TI  - Meningocele in a congolese female with beckwith-wiedemann phenotype.
AB  - Beckwith-Wiedemann syndrome (BWS) is a rare congenital syndrome characterized by
      an overgrowth, macroglossia, exomphalos, and predisposition to embryonal tumors.
      Central nervous abnormalities associated with BWS are rare. We describe a one-day
      old Congolese female who presented meningocele associated with BWS phenotype. 

PMID- 25610674
TI  - Primary hepatic lymphoma in a patient with rheumatoid arthritis treated with
      methotrexate.
AB  - Primary hepatic lymphoma (PHL) has rarely been reported in patients with
      immunosuppression. We herein describe a case of Epstein-Barr virus- (EBV-)
      positive PHL in a 67-year-old Japanese woman receiving methotrexate (MTX)
      treatment for rheumatoid arthritis (RA). The patient, who had been receiving MTX
      therapy for more than 6 years, presented with low-grade fever and abdominal pain.
      Initial laboratory tests showed mildly elevated liver enzymes with normal levels
      of alpha-fetoprotein and carcinoembryonic antigen, and computed tomography scans
      revealed multiple hepatic tumors with no lymph-node swelling. Examination of
      liver specimens obtained via ultrasonography-guided needle biopsy indicated EBV
      positive diffuse large B cell lymphoma; therefore, she was diagnosed with PHL.
      MTX was discontinued, and she was carefully monitored thereafter owing to the
      prolonged history of MTX administration for RA. Rapid progression of PHL was
      observed; therefore 10 days after the PHL diagnosis, she received 6 cycles of R
      THP-COP (rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone)
      therapy and achieved complete remission for more than 1 year. Although MTX
      associated lymphoproliferative disorders often show remission after withdrawal of
      MTX, early diagnosis and treatment are essential for PHL in patients with RA
      treated with MTX, because of the aggressive nature of the disease. 

PMID- 25610675
TI  - Delusions of disseminated fungosis.
AB  - Introduction. Delusional infestation is a rare monosymptomatic hypochondriacal
      psychosis according to The Diagnostic and Statistical Manual of Mental Disorders
      (5th ed.; DSM-5; American Psychiatric Association, 2013). It can be a primary
      disorder or associated with an underlying psychological or physical disorder. It
      commonly presents as delusional parasitosis, and less than 1% may be fungi
      related. We present this case as it is a rare presentation of a rare condition.
      Case Presentation. Our patient is a 60-year-old Caucasian man who presented with
      a 7-year history of delusional infestation manifested as a disseminated fungal
      infection. He had previously been reviewed by multiple physicians for the same
      with no systemic illness diagnosed. After multiple reviews and thorough
      investigation we diagnosed him with a likely delusional disorder. As is common
      with this patient cohort he refused psychiatric review or antipsychotic
      medication. Conclusion. A delusion of a disseminated fungal infestation is a rare
      condition. It is exceedingly difficult to treat as these patients often refuse to
      believe the investigation results and diagnosis. Furthermore, they either refuse
      or are noncompliant with treatment. Multidisciplinary outpatient evaluation may
      be the best way to allay patient fears and improve treatment compliance. 

PMID- 25610676
TI  - Cholangiocarcinoma presenting as uterine metastasis.
AB  - Metastases to the female genital tract are rare, with metastatic disease
      restricted to the uterus being even less frequent. The primary tumor is most
      often intragenital rather than extragenital. The diagnosis is usually made after
      occurrence of gynecological symptoms. We describe the case of a 26-year-old
      female, in whom a curettage for menorrhagia revealed a uterine malignancy, at
      first thought to be a carcinosarcoma. Biochemistry only showed iron deficiency
      anemia. Imaging showed discrepant results with liver lesions, suspect of
      neoplastic or inflammatory disease. She underwent an abdominal hysterectomy and,
      peroperatively, a frozen section of a mass in the liver hilus demonstrated a
      cholangiocarcinoma. The diagnosis of a uterine metastasized cholangiocarcinoma
      was made. We emphasize the fact that uterine metastases have to be excluded in
      every woman with abnormal uterine bleeding and a personal history of malignancy.
      However, our case also indicates that gynecological metastatic disease may be the
      first presentation of an extragenital primary neoplasm. 

PMID- 25610677
TI  - Endometriosis in a patient with mayer-rokitansky-kuster-hauser syndrome.
AB  - Objective. To report a case of Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) in
      which there were two nonfunctional rudimentary uteruses with the presence of
      ovarian endometrioma, corroborating that there are valid alternative theories to
      the existence of endometriosis, rather than Sampson's theory alone, such as the
      coelomic metaplasia theory. Design. A case report. Setting. A tertiary referral
      center, which is also a university hospital. Patient. A fifteen-year-old patient
      with MRKH syndrome and endometriosis. Intervention. Laparoscopic approach for
      diagnostic confirmation and treatment of the endometrioma. Results. Evidence of
      endometriosis in a patient with no functional uterus. Conclusions. This case
      report and a few others that are available in the literature reinforce the
      possibility that coelomic metaplasia could be the origin of endometriosis.
      Patients with mullerian agenesis and pelvic pain should be carefully evaluated,
      and the presence of pelvic endometriosis should not be excluded. 

PMID- 25610678
TI  - Metastatic cerebellar gastrointestinal stromal tumor with obstructive
      hydrocephalus arising from the small intestine: a case report and review of the
      literature.
AB  - Gastrointestinal stromal tumor (GIST) is defined as a c-kit-positive
      gastrointestinal, mesenteric, or omental mesenchymal tumor that very rarely
      metastasizes to the brain. Metastasis to the cerebellum is particularly rare. An
      80-year-old man presented with nausea and vomiting with disturbance of
      consciousness. Magnetic resonance imaging (MRI) revealed tumor in the cerebellar
      vermis causing obstructive hydrocephalus. The patient subsequently underwent
      midline suboccipital craniotomy, and the tumor was totally removed.
      Immunohistochemical analysis showed tumor cells positive for c-kit and CD34, and
      cerebellar metastasis of GIST was diagnosed. Postoperative radiotherapy was
      administered. Following surgery and radiotherapy, the patient developed ileus
      caused by tumor in the small intestine and underwent laparotomy for tumor
      removal. Following abdominal surgery, left hemiparesis and consciousness
      disturbance were noted. Computed tomography showed recurrent large tumor with
      perifocal edema in the right frontal lobe of the brain. The patient died 3 months
      after initial craniotomy. Intracranial metastasis of GIST is extremely rare. In
      cases such as the present, where the condition of the patient rapidly
      deteriorates and features such as rising intracranial pressure and ileus prevent
      the use of oral agents, molecular-targeted agents administered by intravenous
      infusion should be utilized. 

PMID- 25610679
TI  - Chorioretinal atrophy after spontaneous resolution of myopic foveoschisis.
AB  - Myopic foveoschisis is one of the major complications of pathologic myopia, and
      it was most recently identified by new imaging modalities. During the natural
      evolution of this complication, anatomical and visual improvement without
      surgical intervention is an unusual course, and most of these eyes remain stable
      or progressively worsen. The authors report a case of a highly myopic eye that
      developed patchy chorioretinal atrophy after spontaneous resolution of myopic
      foveoschisis, which to the best of our knowledge has not been reported previously
      in the medical literature. 

PMID- 25610680
TI  - Intrapelvic migration of the lag screw in intramedullary nailing.
AB  - Internal fixation with intramedullary devices has gained popularity for the
      treatment of intertrochanteric femoral fractures, which are common injuries in
      the elderly. The most common complications are lag screw cut out from the femoral
      head and femoral fracture at the distal tip of the nail. We report here a rare
      complication of postoperative lag screw migration into the pelvis with no trauma.
      The patient was subsequently treated with lag screw removal and revision surgery
      with total hip arthroplasty. This case demonstrated that optimal fracture
      reduction and positioning of the lag screw are the most important surgical steps
      for decreasing the risk of medial migration of the lag screw. Furthermore, to
      prevent complications, careful attention should be paid to subsequent steps such
      as precise insertion of the set screw. 

PMID- 25610681
TI  - Talectomy for equinovarus deformity in family members with hereditary motor and
      sensory neuropathy type I.
AB  - The treatment of severe rigid neurogenic clubfoot deformities still remains a
      challenging problem in modern paediatric orthopaedics. In those cases, in spite
      of being a palliative procedure, talectomy has been advocated for the correction
      of the deformity thus providing a stable plantigrade foot which allows pain-free
      walking with standard footwear. Herein, we present the results after talectomy in
      two patients (brother and sister) affected by a hereditary motor and sensory
      neuropathy type I, with rigid severe pes equinovarus deformities. 

PMID- 25610682
TI  - Postoperative vision loss after reverse shoulder arthroplasty.
AB  - We report a case which highlights the rare but devastating complication of
      postoperative vision loss (POVL) in orthopaedic surgery. Though documented
      previously, it has not been reported in shoulder arthroplasty surgery of which we
      present the first case. The aetiology of POVL is difficult to elucidate due to
      its elusive nature. We explain the risks associated with regional blocks used for
      such surgery and how this may be related to POVL. We must be vigilant of the
      possible causes of POVL as curative treatment is often not possible and hence
      must take preventative measures which we have recommended. Fortunately, the
      patient fully recovered at 10 months postoperatively with excellent function of
      her reverse shoulder arthroplasty. 

PMID- 25610683
TI  - Use of the composite pedicled pectoralis minor flap after resection of soft
      tissue sarcoma in reconstruction of the glenohumeral joint.
AB  - The surgical repair of an extensive anterior glenohumeral soft tissue defect is
      complicated by glenohumeral instability and subsequent significant functional
      deficit. This surgical note offers a relatively simple reconstruction of the
      anterior capsule and subscapularis muscle using a pectoralis minor pedicle flap.
      This reconstruction is supplemented with functional reconstruction of the
      anterior glenohumeral joint. A conventional deltopectoral approach is utilized
      and pectoralis minor is freed from its coracoid insertion, released, and
      mobilized without compromising the pedicle entering from the dorsum and inferior
      one-third of the muscle. The mobilized pectoralis minor vascular pedicle has
      sufficient length for the pectoralis minor to be transferred to provide coverage
      of the anterior shoulder joint even in full external rotation, providing anterior
      stability. To further improve glenohumeral stability and shoulder function, the
      pectoralis major muscle can be split with the clavicular part reinserted lateral
      to the bicipital groove onto the lesser tuberosity replacing subscapularis
      function while stabilising the glenohumeral joint. 

PMID- 25610684
TI  - Chronic Expanding Hematoma in the Popliteal Fossa after Pseudoaneurysm Surgery
      because of Nail Puncture.
AB  - Hematomas caused by surgery or trauma that persist and expand slowly for more
      than a month are defined as chronic expanding hematomas (CEH). Magnetic resonance
      imaging (MRI) is useful for the diagnosis. Total excision with the pseudocapsule
      is the treatment method. Pseudoaneurysms result from arterial wall disruptions
      and can be mistaken for CEH. We present a rare case report of a 45-year-old man
      with a large, painful swelling in his left popliteal fossa. He had a puncture
      wound by a nail 11 years ago and a gradually expanding mass occurred in his
      popliteal fossa. A pseudoaneurysm was detected and operated a year later. After
      surgery, a gradually expanding mass recurred in his popliteal fossa. On the
      arteriography, the popliteal artery was occluded and the blood flow was
      maintained with collateral vessels. On MRI, an enormous swelling of 115 * 107 *
      196 cm in diameter was seen. It was diagnosed as CEH and was excised completely
      protecting the collateral vessels and there was no recurrence after a year from
      the surgery. 

PMID- 25610685
TI  - Olfactory loss after uvulopalatopharyngoplasty: a report of two cases with review
      of the literature.
AB  - Uvulopalatopharyngoplasty (UPPP) has been a popular surgical method for treating
      obstructive sleep apnea syndrome since it was introduced in the early 1980s.
      Olfactory loss has been reported as a rare side effect in several cases. However,
      the olfactory test results and the prognosis were not mentioned in these cases.
      We present two patients who complained of loss of olfactory function after UPPP.
      Their olfactory function was evaluated by the phenyl ethyl alcohol odor detection
      threshold test and the University of Pennsylvania Smell Identification Test.
      After treatment with steroid and zinc salt, their olfactory function was improved
      but not recovered completely. 

PMID- 25610686
TI  - Primary synovial sarcoma of kidney: a rare differential diagnosis of renomegaly.
AB  - Synovial sarcomas (SS) are classified as subgroup of soft tissue sarcomas
      affecting mainly extremities of young adults. Primary SS of kidney are very rare
      tumours with poor prognosis. Though they have characteristic histology and
      immunohistochemistry (IHC) due to rarity of incidence it is difficult to diagnose
      them. Sometimes chromosomal rearrangement studies are required to confirm the
      diagnosis. We are presenting a case of 41-year-old male who was referred to our
      cancer centre for evaluation of left renal mass. CT scan of abdomen revealed a
      large left renal mass encasing the aorta. Biopsy of renal mass revealed poorly
      differentiated sarcoma and IHC was positive for vimentin, CD99, and BCL2 and
      negative for AE1, epithelial membrane antigen, and leukocyte common antigen. The
      patient was clinically inoperable as renal mass was encasing the aorta. So he was
      subsequently offered palliative chemotherapy in form of ifosfamide and
      adriamycin. CT abdomen shows partial response after 3 cycles of chemotherapy
      according to RECIST criteria. 

PMID- 25610687
TI  - A rare soft tissue tumor masquerading as a parathyroid adenoma in a patient with
      birt-hogg-dube syndrome and multiple cervical endocrinopathies.
AB  - Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disorder that presents
      with renal tumors, pulmonary cysts with spontaneous pneumothoraces, and skin
      hamartomas. We present a case of a 67-year-old female with multiple
      endocrinopathies and a history of BHD syndrome. In 2011, a thyroidectomy with a
      four-gland parathyroidectomy was performed for toxic multinodular goiter (TMNG)
      and parathyroid hyperplasia. On frozen section, a tumor was identified next to a
      hypercellular parathyroid. After being worked up, this tumor was determined to be
      an adult rhabdomyoma. This represents the first time that both TMNG and
      parathyroid hyperplasia have been present in a BHD patient. Additionally, this is
      the first adult rhabdomyoma reported in a patient with BHD syndrome. Adult
      rhabdomyomas have no reported associations; however, potential colocation of the
      mutation in BHD syndrome and translocation in adult rhabdomyomas on chromosome
      17p suggests a possible connection. Further work is needed to better understand
      this connection. 

PMID- 25610688
TI  - A Case of Acute Myeloid Leukemia (FAB M2) with Inversion 16 Who Presented with
      Pelvic Myeloid Sarcoma.
AB  - Acute leukemias are the most common childhood cancer in all age groups. Acute
      myeloid leukemias (AML) constitute about 15-20% of acute leukemias. Fatigability,
      pallor, fever, and bleeding are the most common presenting symptoms of AML.
      Hepatosplenomegaly and lymphadenopathy are commonly encountered during physical
      examination. In rare instances eruptions due to skin involvement and localized
      tumor masses (myeloid sarcoma) may be found. Myeloid sarcoma is especially seen
      in AML-M2 subtype. By cytogenetic analysis, in AML-M2 subtype t(8;21) is often
      seen and it is more probable to find inversion 16 in AML-M4Eos subtype. Herein,
      we present a 15-year-old girl whose initial symptom was abdominal pain for three
      days and her pathological sign was a large abdominal mass which was verified by
      imaging studies and diagnosed as myeloid sarcoma by biopsy. On bone marrow
      examination, she had diagnosis of AML-M2 and by cytogenetic analysis inversion 16
      was positive. She was treated with AML-BFM 2004 protocol and she is being
      followed up in remission on her ninth month of the maintenance therapy. 

PMID- 25610689
TI  - Atypical presentation of cat-scratch disease in an immunocompetent child with
      serological and pathological evidence.
AB  - Typical cat-scratch disease (CSD) is characterized by local lymphadenopathy
      following the scratch or bite from a cat or kitten. An atypical presentation
      which includes liver and/or spleen lesions is rarely reported in an
      immunocompetent child. Systemic CSD may mimic more serious disorders like
      malignancy or tuberculosis. Although a diagnosis is difficult to establish in
      systemic CSD, an early diagnosis and an appropriate treatment are important to
      prevent complications. Bartonella henselae is difficult to culture, and culture
      is not routinely recommended. Clinical, serological, radiological, and
      pathological findings are used for the diagnosis of CSD. Herein we present a case
      of systemic CSD presenting with hepatic mass in an immunocompetent child. The
      differential diagnosis is made by serological and pathological evidence. He was
      successfully treated with gentamicin (7.5 mg/kg) and rifampin (15 mg/kg) for six
      weeks. 

PMID- 25610690
TI  - Necrotizing fasciitis of the chest in a neonate in southern Nigeria.
AB  - We discuss the successful saving of a male neonate with necrotizing fasciitis of
      the chest following a hot fomentation of the umbilicus with exposure of the ribs
      and the pleural space on the right side. He recovered 5 weeks after admission. We
      stressed the need to recognize necrotizing fasciitis extending from the upper
      anterior abdominal wall to the chest following hot fomentation of the umbilicus.
      The need for multidisciplinary cooperation for excellent outcome is very
      important, that is, neonatologist, medical microbiologist, and plastic and chest
      surgeons. 

PMID- 25610691
TI  - Severe growing-up phobia, a condition explained in a 14-year-old boy.
AB  - We present the clinical case of a 14-year-old boy with gerascophobia or an
      excessive fear of aging, who felt his body development as a threat, to the point
      where he took extreme measures to stop or otherwise hide growth. He had a history
      of separation anxiety, sexual abuse, and suffering bullying. He presented with
      anxious and depressive symptoms and food restriction, criticized his body image,
      had negative feelings towards the maturation process, suffered at the thought of
      being rejected, and was preoccupied with certain physical characteristics. We
      conducted an analysis of biological, psychological, and environmental factors and
      their possible interactions and established treatment with psychotherapy and
      fluoxetine. Because of the favorable results, this approach could be considered a
      good option in such cases. 

PMID- 25610692
TI  - The first described case of occupational anthracofibrosis in the USA.
AB  - Anthracofibrosis is a newly recognized disease that was first described in
      association with tuberculosis in 1998 in Korea. However, recent reports suggest
      strong association with biomass fuel smoke exposure, and exposure to mineral
      dusts, coal, silica, and mica. Most of the reported cases to date are in patients
      from Asia or in immigrants of Asian origin. There are no published reports of
      anthracofibrosis in the USA. We present the first case of a USA born African
      American male patient with anthracofibrosis. 

PMID- 25610693
TI  - Stenting as a rescue treatment of a pulmonary artery false aneurysm caused by
      swan-ganz catheterization.
AB  - Pulmonary vascular injury is a rare but life-threatening complication of Swan
      Ganz catheterization. We report an 82-year old patient who underwent right heart
      catheterization by a balloon-tipped catheter because of suspected pulmonary
      hypertension. After deflation of the catheter in the wedge position, hemoptoe
      appeared associated with acute respiratory insufficiency requiring respiratory
      support by intubation and mechanical ventilation. Pulmonary angiography showed
      the formation of a false aneurysm of a segment artery of the left lower lobe.
      Immediate interventional therapy was performed by the implantation of two coated
      coronary stent grafts into the injured pulmonary artery thereby excluding the
      false aneurysm. Bleeding was stopped by this interventional approach while
      antegrade blood flow was maintained. Long term follow-up after 3 months showed an
      effective treatment with a completely thrombotic false aneurysm. However, despite
      oral anticoagulation and dual antiplatelet therapy, graft patency could not be
      achieved after 3 months. In summary, implantation of coated stents is a feasible
      and safe approach for the acute and long term treatment of potentially life
      threatening condition of a pulmonary artery false aneurysm while treatment to
      achieve long term patency of the affected vessel still remains an issue to be
      resolved. 

PMID- 25610694
TI  - Three-Dimensional CT Findings of Os Calcaneus Secundarius Mimicking a Fracture.
AB  - Os calcaneus secundarius is one of several accessory ossicles of the foot that
      have been identified as normal variants of skeletal development. It may cause
      ankle pain and may mimic an avulsion fracture of the anterior calcaneal process.
      A twenty-year-old male was admitted to our institution with right ankle pain
      following an inversion injury. An axial CT image of the patient's right ankle
      revealed a shape with smooth and sharp margins, identified as a well-corticated
      bone fragment in the subtalar region. A diagnosis of an accessory ossicle, os
      calcaneus secundarius, was made based on radiographic findings. As a result of
      this case, it is recommended that potential locations of the accessory bones
      should be well understood in order to prevent misdiagnosis and inappropriate
      surgical procedures. Os calcaneus secundarius must be considered when an apparent
      bone fragment or a suspicious fracture line at the anterior region of os
      calcaneus is demonstrated. 

PMID- 25610695
TI  - Dealing with a Porcelain Aorta during Coronary Artery Bypass Grafting.
AB  - We report a complex case of multivessel CAD in a patient with a porcelain aorta
      and high-grade left subclavian artery stenosis. Utilizing a staged left
      subclavian artery stent placement with a next-day plan for a four-vessel, on-pump
      CABG and ascending aortic replacement, this case highlights an organized approach
      to diagnosing and dealing with a heavily calcified aorta while describing a
      stepwise algorithm to deal with aortic calcifications prior to initiating cardiac
      surgery. 

PMID- 25610696
TI  - Resection of a catecholamine-elaborating retroperitoneal paraganglioma invading
      the inferior vena cava.
AB  - Paragangliomas are rare tumors originating outside of the adrenal medulla which
      can be associated with catecholamine secretion or mass effect, one of which
      typically leads to their discovery. The differences between these tumors and
      traditional intra-adrenal pheochromocytomas are a subject of recent
      investigations. Standard of care therapy is medical management and surgical
      resection of the tumor. When tumors are biochemically active, medical
      optimization of the autonomic nervous system is a critical component to a safe,
      definitive resection. Tumors arising in the retroperitoneum present technical
      challenges for the surgeon as they are often large and difficult to access,
      making an oncologic resection much more difficult. Lastly, these tumors are
      mostly benign and rarely invade adjacent structures-an operative finding not
      always predicted by preoperative imaging-which, if present, adds significant
      complexity and risk to the resection. A case illustrating these challenges in the
      management of a biochemically active retroperitoneal paraganglioma invading the
      inferior vena cava follows. 

PMID- 25610697
TI  - Sterile acellular dermal collagen as a treatment for rippling deformity of
      breast.
AB  - Prosthetic implants are frequently used for breast augmentation and breast
      reconstruction following mastectomy. Unfortunately, long-term aesthetic results
      of prosthetic breast restoration may be hindered by complications such as
      rippling, capsular contracture, and implant malposition. The advent of use of
      acellular dermal matrices has greatly improved the outcomes of prosthetic breast
      reconstruction. We describe a case of rippling deformity of breast that was
      treated using an acellular dermal matrix product, AlloMax. The patient presented
      with visible rippling of bilateral prosthetic breast implants as well as
      significant asymmetry of the breasts after multiple excisional biopsies for right
      breast ductal carcinoma in situ. A 6 * 10 cm piece of AlloMax was placed on the
      medial aspect of each breast between the implant and the skin flap. Follow-up was
      performed at 1 week, 3 months, and 1 year following the procedure. The patient
      recovered well from the surgery and there were no complications. At her first
      postoperative follow-up the patient was extremely satisfied with the result. At
      her 3-month and 1-year follow-up she had no recurrence of her previous deformity
      and no new deformity. 

PMID- 25610698
TI  - Delayed gastric emptying after living donor hepatectomy for liver
      transplantation.
AB  - Delayed gastric emptying is a significant postoperative complication of living
      donor hepatectomy for liver transplantation and may require endoscopic or
      surgical intervention in severe cases. Although the mechanism of posthepatectomy
      delayed gastric emptying remains unknown, vagal nerve injury during
      intraoperative dissection and adhesion formation postoperatively between the
      stomach and cut liver surface are possible explanations. Here, we present the
      first reported case of delayed gastric emptying following fully laparoscopic
      hepatectomy for living donor liver transplantation. Additionally, we also present
      a case in which symptoms developed after open right hepatectomy, but for which
      dissection for left hepatectomy was first performed. Through our experience and
      these two specific cases, we favor a neurovascular etiology for delayed gastric
      emptying after hepatectomy. 

PMID- 25610699
TI  - Possible complications of ureteroscopy in modern endourological era: two-point or
      "scabbard" avulsion.
AB  - Indication has led ureteroscopy to be a worldwide technique, with the expected
      appearance of multiple types of complications. Severe complications are possible
      including ureteral perforation or avulsion. Ureteral avulsion has been described
      as an upper urinary tract injury related to the action of blunt trauma,
      especially from traffic accidents, being the mechanism of injury, the result of
      an acute deceleration/acceleration movement. With the advent of endourology, that
      term is also applied to the extensive degloving injury resulting from a mechanism
      of stretching of the ureter that eventually breaks at the most weakened site, or
      ureteral avulsion is referred to as a discontinuation of the full thickness of
      the ureter. The paper presents a case report and literature review of the two
      point or "scabbard" avulsion. The loss of long segment of the upper ureter, when
      end-to-end anastomosis is not technically feasible, presents a challenge to the
      urological surgeon. In the era of small calibre ureteroscopes these
      complications, due to growing incidence of renal stones will become more and more
      actual. Our message to other urologists is to know such a complication, to know
      the ways of treatment, and to analyse ureteroscopic signs, when to stop or pay
      attention. 

PMID- 25610700
TI  - Delayed migration of embolized coil with large renal stone formation: a rare
      presentation.
AB  - Delayed bleeding following percutaneous nephrolithotomy (PCNL) usually occurs due
      to development of the pseudoaneurysm which can be successfully managed with coil
      embolization. However very few cases of such complications have been reported in
      the literature. Here we are reporting a case of delayed post-PCNL bleeding that
      occurred in a 53-year-old diabetic patient operated on for renal stone. Computed
      tomography scan revealed a presence of the pseudoaneurysm in the segmental branch
      of right renal artery, which was successfully managed with coiling. Patient
      remained asymptomatic for the next 9 years after which he again presented with
      similar complaints. X-ray KUB was done which revealed a 2.7 cms renal pelvic
      calculus with the migrated coil in its center and a left upper ureteric calculus.
      His routine haemogram, coagulogram, serum electrolytes, and liver function tests,
      renal function tests, vitamin D3, and PTH (parathyroid hormone) were within
      normal limits. He underwent left laparoscopic ureterolithotomy and right
      percutaneous nephrolithotomy (PCNL). Intraoperatively the migrated stainless
      steel embolization coil was seen engulfed all around by the multiple stones in
      the right renal pelvis. Postoperative period was uneventful. Later he was
      followed in the outpatient department and was doing well. To conclude, this is
      the only case report of development of a large calculus around a migrated
      embolization coil which was successfully managed with PCNL. PCNL offers better
      stone clearance in cases of stones being formed over foreign bodies like
      fragmented double J stents, fragmented nephrostomies, or migrated embolization
      coil. 

PMID- 25610701
TI  - Successful endovascular treatment of iatrogenic thyrocervical trunk
      pseudoaneurysm with concomitant arteriovenous fistula using 0.010-inch detachable
      microcoils.
AB  - Pseudoaneurysms (PsA) and arteriovenous fistulae (AVF) of the thyrocervical trunk
      and its branches are rare complications of traumatic or iatrogenic arterial
      injuries. Most such injuries are iatrogenic and are associated with central
      venous catheterization. Historically, thyrocervical trunk PsA and AVF have been
      managed with open surgical repair; however, multiple treatment modalities are now
      available, including ultrasound-guided compression repair, ultrasound-guided
      thrombin injection, and endovascular repair with covered stent placement. We
      report a case of a 65-year-old woman with an iatrogenic thyrocervical trunk PsA
      with concomitant AVF that developed after attempted internal jugular vein
      cannulation for hemodialysis access. The PsA was successfully treated by
      transcatheter coil embolization using 0.010-inch detachable microcoils. Our case
      is the first published instance of a thyrocervical trunk PsA with concomitant AVF
      that was successfully treated by endovascular procedure. 

PMID- 25610702
TI  - Network Analysis of Plasmidomes: The Azospirillum brasilense Sp245 Case.
AB  - Azospirillum brasilense is a nitrogen-fixing bacterium living in association with
      plant roots. The genome of the strain Sp245, isolated in Brazil from wheat roots,
      consists of one chromosome and six plasmids. In this work, the A. brasilense
      Sp245 plasmids were analyzed in order to shed some light on the evolutionary
      pathways they followed over time. To this purpose, a similarity network approach
      was applied in order to identify the evolutionary relationships among all the A.
      brasilense plasmids encoded proteins; in this context a computational pipeline
      specifically devoted to the analysis and the visualization of the network-like
      evolutionary relationships among different plasmids molecules was developed. This
      information was supplemented with a detailed (in silico) functional
      characterization of both the connected (i.e., sharing homology with other
      sequences in the dataset) and the unconnected (i.e., not sharing homology)
      components of the network. Furthermore, the most likely source organism for each
      of the genes encoded by A. brasilense plasmids was checked, allowing the
      identification of possible trends of gene loss/gain in this microorganism. Data
      obtained provided a detailed description of the evolutionary landscape of the
      plasmids of A. brasilense Sp245, suggesting some of the molecular mechanisms
      responsible for the present-day structure of these molecules. 

PMID- 25610703
TI  - Vasospasm in cerebral inflammation.
AB  - All forms of cerebral inflammation as found in bacterial meningitis, cerebral
      malaria, brain injury, and subarachnoid haemorrhage have been associated with
      vasospasm of cerebral arteries and arterioles. Vasospasm has been associated with
      permanent neurological deficits and death in subarachnoid haemorrhage and
      bacterial meningitis. Increased levels of interleukin-1 may be involved in
      vasospasm through calcium dependent and independent activation of the myosin
      light chain kinase and release of the vasoconstrictor endothelin-1. Another key
      factor in the pathogenesis of cerebral arterial vasospasm may be the reduced
      bioavailability of the vasodilator nitric oxide. Therapeutic trials in vasospasm
      related to inflammation in subarachnoid haemorrhage in humans showed a reduction
      of vasospasm through calcium antagonists, endothelin receptor antagonists,
      statins, and plasminogen activators. Combination of therapeutic modalities
      addressing calcium dependent and independent vasospasm, the underlying
      inflammation, and depletion of nitric oxide simultaneously merit further study in
      all conditions with cerebral inflammation in double blind randomised placebo
      controlled trials. Auxiliary treatment with these agents may be able to reduce
      ischemic brain injury associated with neurological deficits and increased
      mortality. 

PMID- 25610704
TI  - Anti-inflammatory and antiarthritic activity of anthraquinone derivatives in
      rodents.
AB  - Aloe emodin is isolated compound of aloe vera which is used traditionally as an
      anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl
      or sulfated forms of aloe emodin may provide some limitations in its absorption
      capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity
      due to inhibition of inducible nitric oxide (iNO) and prostaglandin E2, via its
      action on murine macrophages. However, present work evidenced that molecular
      docking of aloe emodin modulates the anti-inflammatory activity, as well as
      expression of COX-2 (cyclooxygenase-2) in rodent. The AEC (4,5-dihydroxy-9,10
      dioxo-9,10-dihydroanthracene-2 carboxylic acid) was synthesized using aloe emodin
      as starting material. The study was planned for evaluation of possible anti
      inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and
      complete Freund's adjuvant induced arthritis in rats. The AE (aloe emodin) and
      AEC significantly (P < 0.001) reduced carrageenan induced paw edema at 50 and 75
      mg/kg. Complete Freund's adjuvant induced arthritis model showed significant (P <
      0.001) decrease in injected and noninjected paw volume, arthritic score. AE and
      AEC showed significant effect on various biochemical, antioxidant, and
      hematological parameters. Diclofenac sodium 10 mg/kg showed significant (P <
      0.001) inhibition in inflammation and arthritis. 

PMID- 25610705
TI  - Elevated Serum Thyroglobulin and Low Iodine Intake Are Associated with Nontoxic
      Nodular Goiter among Adults Living near the Eastern Mediterranean Coast.
AB  - Background. Information about iodine intake is crucial for preventing thyroid
      diseases. Inadequate iodine intake can lead to thyroid diseases, including
      nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore
      its correlation with thyroid diseases among Israeli adults living near the
      Mediterranean coast, where iodine-depleted desalinated water has become a major
      source of drinking water. Methods. Cross-sectional study of patients attending
      Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG
      (n = 17), hypothyroidism (n = 14), or control (n = 31), provided serum
      thyroglobulin (Tg) and completed a semiquantitative iodine food frequency
      questionnaire. Results. Elevated serum Tg values (Tg > 60 ng/mL) were
      significantly more prevalent in the NNG group than in the other groups (29%
      versus 7% and 0% for hypothyroidism and controls, resp., P < 0.05). Mean
      estimated iodine intake was significantly lower in the NNG group (65 +/- 30
      MUg/d) than in controls (115 +/- 60 MUg/d) (P < 0.05) with intermediate intake in
      the hypothyroid group (73 +/- 38 MUg/d). Conclusions. Elevated serum Tg values
      and low dietary iodine intake are associated with NNG among adult patients in
      Ashkelon District, Israel. Larger studies are needed in order to expand on these
      important initial findings. 

PMID- 25610706
TI  - Polysomnographic Features of Sleep Disturbances and REM Sleep Behavior Disorder
      in the Unilateral 6-OHDA Lesioned Hemiparkinsonian Rat.
AB  - Sleep pattern disruption, specifically REM sleep behavior disorder (RBD), is a
      major nonmotor cause of disability in PD. Understanding the pathophysiology of
      these sleep pattern disturbances is critical to find effective treatments. 24
      hour polysomnography (PSG), the gold standard for sleep studies, has never been
      used to test sleep dysfunction in the standard 6-OHDA lesioned hemiparkinsonian
      (HP) rat PD model. In this study, we recorded 24-hour PSG from normal and HP
      rats. Recordings were scored into wake, rapid eye movement (REM), and non-REM
      (NREM). We then examined EEG to identify REM periods and EMG to check muscle
      activity during REM. Normal rats showed higher wakefulness (70-80%) during the
      dark phase and lower wakefulness (20%) during the light phase. HP rats showed 30
      50% sleep in both phases, less modulation and synchronization to the light
      schedule (P < 0.0001), and more long run lengths of wakefulness (P < 0.05). HP
      rats also had more REM epochs with muscle activity than control rats (P < 0.05).
      Our findings that the sleep architecture in the HP rat resembles that of PD
      patients demonstrate the value of this model in studying the pathophysiological
      basis of PD sleep disturbances and preclinical therapeutics for PD related sleep
      disorders including RBD. 

PMID- 25610707
TI  - Respiratory diseases of small ruminants.

PMID- 25610709
TI  - Combining targeted therapy and immune checkpoint inhibitors in the treatment of
      metastatic melanoma.
AB  - Melanoma is the deadliest form of skin cancer and has an incidence that is rising
      faster than any other solid tumor. Metastatic melanoma treatment has considerably
      progressed in the past five years with the introduction of targeted therapy (BRAF
      and MEK inhibitors) and immune checkpoint blockade (anti-CTLA4, anti-PD-1, and
      anti-PD-L1). However, each treatment modality has limitations. Treatment with
      targeted therapy has been associated with a high response rate, but with short
      term responses. Conversely, treatment with immune checkpoint blockade has a lower
      response rate, but with long-term responses. Targeted therapy affects antitumor
      immunity, and synergy may exist when targeted therapy is combined with
      immunotherapy. This article presents a brief review of the rationale and evidence
      for the potential synergy between targeted therapy and immune checkpoint
      blockade. Challenges and directions for future studies are also proposed. 

PMID- 25610708
TI  - Minimally invasive local therapies for liver cancer.
AB  - Primary and metastatic liver tumors are an increasing global health problem, with
      hepatocellular carcinoma (HCC) now being the third leading cause of cancer
      related mortality worldwide. Systemic treatment options for HCC remain limited,
      with Sorafenib as the only prospectively validated agent shown to increase
      overall survival. Surgical resection and/or transplantation, locally ablative
      therapies and regional or locoregional therapies have filled the gap in liver
      tumor treatments, providing improved survival outcomes for both primary and
      metastatic tumors. Minimally invasive local therapies have an increasing role in
      the treatment of both primary and metastatic liver tumors. For patients with low
      volume disease, these therapies have now been established into consensus practice
      guidelines. This review highlights technical aspects and outcomes of commonly
      utilized, minimally invasive local therapies including laparoscopic liver
      resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high
      intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and
      stereotactic body radiation therapy (SBRT). In addition, the role of combination
      treatment strategies utilizing these minimally invasive techniques is reviewed. 

PMID- 25610710
TI  - Recent advances in lymphatic targeted drug delivery system for tumor metastasis.
AB  - The lymphatic system has an important defensive role in the human body. The
      metastasis of most tumors initially spreads through the surrounding lymphatic
      tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even
      transfer to other organs to form other types of tumors. Clinically, lymphatic
      metastatic tumors develop rapidly. Given the limitations of surgical resection
      and the low effectiveness of radiotherapy and chemotherapy, the treatment of
      lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may
      lead to the further spread of tumors and may be predictive of the endpoint event.
      Under these circumstances, novel and effective lymphatic targeted drug delivery
      systems have been explored to improve the specificity of anticancer drugs to
      tumor cells in lymph nodes. In this review, we summarize the principles of
      lymphatic targeted drug delivery and discuss recent advances in the development
      of lymphatic targeted carriers. 

PMID- 25610712
TI  - Argyrophilic nucleolar organizer region in MIB-1 positive cells in non-small cell
      lung cancer: clinicopathological significance and survival.
AB  - OBJECTIVE: To evaluate the relation between argyrophilic nucleolar organizer
      region (AgNOR)-associated proteins and clinicopathological parameters and
      survival in non-small-cell lung cancer (NSCLC). METHODS: A total of 207 surgical
      specimens diagnosed as NSCLC were included in this study. Double-staining
      procedures were performed using antigen Ki-67 (clone MIB-1) and silver nitrate by
      immunohistochemical and AgNOR-staining methods. RESULTS: The AgNOR area in MIB-1
      positive cells of NSCLC is related to clinicopathological parameters under the
      TNM (tumor, node, and metastasis) system. The survival of patients with small
      AgNOR area in MIB-1-positive cells is better than that of patients with large
      AgNOR area. Molecular, biological (AgNOR area in MIB-1-positive cells), and
      clinicopathological (greatest tumor dimension, metastases to regional lymph
      nodes, histology, and differentiation) parameters are independent prognostic
      factors of NSCLC. CONCLUSION: The AgNOR area in MIB-1-positive cells is related
      to clinicopathological parameters and survival in NSCLC.

PMID- 25610714
TI  - Sequential maximum androgen blockade (MAB) in minimally symptomatic prostate
      cancer progressing after initial MAB: two case reports.
AB  - The management of castrate-resistant prostate cancer progressing after maximum
      androgen blockade (MAB) has evolved in the last decade with the development of
      several novel therapeutic options. However, the initial therapeutic strategy in
      these patients usually involves withdrawal of anti-androgen that can be
      associated with biochemical response in approximately 20% of patients. Notably,
      we have observed evidence of sustained biochemical response in two patients
      following second- and third-line MAB using rechallenge schedule of previously
      administered anti-androgen after latent interval. The possibility of response
      following sequential MAB using the same anti-androgen agent has not yet been
      reported. 

PMID- 25610715
TI  - Report on the 9(th) International Congress on Peritoneal Surface Malignancies.

PMID- 25610711
TI  - Emerging function of mTORC2 as a core regulator in glioblastoma: metabolic
      reprogramming and drug resistance.
AB  - Glioblastoma (GBM) is one of the most lethal human cancers. Genomic analyses
      define the molecular architecture of GBM and highlight a central function for
      mechanistic target of rapamycin (mTOR) signaling. mTOR kinase exists in two multi
      protein complexes, namely, mTORC1 and mTORC2. These complexes differ in terms of
      function, regulation and rapamycin sensitivity. mTORC1 is well established as a
      cancer drug target, whereas the functions of mTORC2 in cancer, including GBM,
      remains poorly understood. This study reviews the recent findings that
      demonstrate a central function of mTORC2 in regulating tumor growth, metabolic
      reprogramming, and targeted therapy resistance in GBM, which makes mTORC2 as a
      critical GBM drug target. 

PMID- 25610713
TI  - Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell
      lung cancer patients who underwent EGFR-TKI.
AB  - OBJECTIVE: Non-small cell lung cancer (NSCLC) patients with epidermal growth
      factor receptor (EGFR)-activating mutations have higher response rate and more
      prolonged survival following treatment with single-agent EGFR tyrosine kinase
      inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all
      patients treated with reversible inhibitors develop acquired resistance over
      time. The mechanisms of resistance are complicated. The lack of established
      therapeutic options for patients after a failed EGFR-TKI treatment poses a great
      challenge to physicians in managing this group of lung cancer patients. This
      study evaluates the influence of EGFR-TKI retreatment following chemotherapy
      after failure of initial EGFR-TKI within at least 6 months on NSCLC patients.
      METHODS: The data of 27 patients who experienced treatment failure from their
      initial use of EGFR-TKI within at least 6 months were analyzed. After
      chemotherapy, the patients were retreated with EGFR-TKI (gefitinib 250 mg qd or
      erlotinib 150 mg qd), and the tumor progression was observed. The patients were
      assessed for adverse events and response to therapy. Targeted tumor lesions were
      assessed with CT scan. RESULTS: Of the 27 patients who received EGFR-TKI
      retreatment, 1 (3.7%) patient was observed in complete response (CR), 8 (29.6%)
      patients in partial response (PR), 14 (51.9%) patients in stable disease (SD),
      and 4 (14.8%) patients in progressive disease (PD). The disease control rate
      (DCR) was 85.2% (95% CI: 62%-94%). The median progression-free survival (mPFS)
      was 6 months (95% CI: 1-29). Of the 13 patients who received the same EGFR-TKI, 1
      patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were
      observed. The DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who
      received another EGFR-TKI, no patient in CR, 6 patients in PR, 6 patients in SD,
      and 2 patients in PD were observed. The DCR was 85.7%, and the mPFS was 9.5
      months. Significant difference was found between the two groups in PFS but not in
      response rate or DCR. CONCLUSION: Retreatment of EGFR-TKIs can be considered an
      option after failure of chemotherapy for patients who were previously controlled
      by EGFR-TKI treatment.

PMID- 25610716
TI  - Is the model of signal amplification by GPCRs/GEFs activating multiple GTPases
      relevant to a broad spectrum of heterotrimeric and RAS superfamily GTPases?
AB  - Concepts or models of biological processes shape how we think about them, discuss
      them, and design experiments to test aspects of them. Because of the importance
      of our models of cell signaling by regulatory GTPases and the desire to extend
      those models to related signaling modules, I have throughout my career been
      fascinated by the similarities and differences between the modeling of
      heterotrimeric G protein and monomeric RAS superfamily GTPases. Recent
      discussions with colleagues led me to conclude that there is a growing divergence
      in how researchers model the activation and signaling processes of monomeric and
      trimeric GTPases and also a surprising lack of consensus within each camp. This
      series of articles arose in response to these discussions and is intended to
      spark new ones.

PMID- 25610717
TI  - GEF-effector interactions.
AB  - Members of the Arf family of small GTP-binding proteins, or GTPases, are
      activated by guanine nucleotide exchange factors (GEFs) that catalyze GDP release
      from their substrate Arf, allowing GTP to bind. In the secretory pathway, Arf1 is
      first activated by GBF1 at the cis-Golgi, then by BIG1 and BIG2 at the trans
      Golgi and trans-Golgi network (TGN). Upon activation, Arf1-GTP interacts with
      effectors such as coat complexes, and is able to recruit different coat complexes
      to different membrane sites in cells. The COPI coat is primarily recruited to cis
      Golgi membranes, whereas other coats, such as AP-1/clathrin, and GGA/clathrin,
      are recruited to the trans-Golgi and the TGN. Although Arf1-GTP is required for
      stable association of these various coats to membranes, and is sufficient in
      vitro, other molecules, such as vesicle cargo and coat receptors on the membrane,
      contribute to specificity of coat recruitment in cells. Another mechanism to
      achieve specificity is interaction of effectors such as coats with the GEF
      itself, which would increase the concentration of a given coat in proximity to
      the site where Arf is activated, thus favoring its recruitment. This interaction
      between a GEF and an effector could also provide a mechanism for spatial
      organization of vesicle budding sites, similar to that described for Cdc42
      mediated establishment of polarity sites such as the emerging bud in yeast.
      Another factor affecting the amount of freely diffusible Arf1-GTP in membranes is
      the GEF(s) themselves acting as effectors. Sec7p, the yeast homolog of mammalian
      BIG1 and BIG2, and Arno/cytohesin 2, a PM-localized Arf1 GEF, both bind to Arf1
      GTP. This binding to the products of the exchange reaction establishes a positive
      feedback loop for activation.

PMID- 25610718
TI  - Spatial and temporal control of Rho GTPase functions.
AB  - Rho family GTPases control almost every aspect of cell physiology and, since
      their discovery, a wealth of knowledge has accumulated about their biochemical
      regulation and function. However, each Rho GTPase distributes between multiple
      cellular compartments, even within the same cell, where they are controlled by
      multiple regulators and signal to multiple effectors. Thus, major questions about
      spatial and temporal aspects of regulation remain unanswered. In particular, what
      are the nano-scale dynamics for their activation, membrane targeting, diffusion,
      effector activation and GTPase inactivation? How do these mechanisms differ in
      the different cellular compartments where Rho GTPases function? Addressing these
      complex aspects of Rho GTPase biology will significantly advance our
      understanding of the spatial and temporal control of cellular functions.

PMID- 25610720
TI  - AKAP350C targets to mitochondria via a novel amphipathic alpha helical domain.
AB  - Mitochondria regulate metabolism and homeostasis within cells. Mitochondria are
      also very dynamic organelles, constantly undergoing fission and fusion. The
      importance of maintaining proper mitochondrial dynamics is evident in the various
      diseases associated with defects in these processes. Protein kinase A (PKA) is a
      key regulator of mitochondrial dynamics. PKA is spatially regulated by A-Kinase
      Anchoring Proteins (AKAPs). We completed cloning of a novel AKAP350 isoform,
      AKAP350C. Immunostaining for endogenous AKAP350C showed localization to
      mitochondria. The carboxyl-terminal 54-amino acid sequence unique to AKAP350C
      contains a novel amphipathic alpha helical mitochondrial-targeting domain.
      AKAP350C co-localizes with Mff (mitochondrial fission protein) and mitofusins 1
      and 2 (mitochondrial fusion proteins), and likely regulates mitochondrial
      dynamics by scaffolding PKA and mitochondrial fission and fusion proteins.

PMID- 25610719
TI  - Class C ABC transporters and Saccharomyces cerevisiae vacuole fusion.
AB  - Membrane fusion is carried out by core machinery that is conserved throughout
      eukaryotes. This is comprised of Rab GTPases and their effectors, and SNARE
      proteins, which together are sufficient to drive the fusion of reconstituted
      proteoliposomes. However, an outer layer of factors that are specific to
      individual trafficking pathways in vivo regulates the spatial and temporal
      occurrence of fusion. The homotypic fusion of Saccharomyces cerevisiae vacuolar
      lysosomes utilizes a growing set of factors to regulate the fusion machinery that
      include members of the ATP binding cassette (ABC) transporter family. Yeast
      vacuoles have five class C ABC transporters that are known to transport a variety
      of toxins into the vacuole lumen as part of detoxifying the cell. We have found
      that ABCC transporters can also regulate vacuole fusion through novel mechanisms.
      For instance Ybt1 serves as negative regulator of fusion through its effects on
      vacuolar Ca2+ homeostasis. Additional studies showed that Ycf1 acts as a positive
      regulator by affecting the efficient recruitment of the SNARE Vam7. Finally, we
      discuss the potential interface between the translocation of lipids across the
      membrane bilayer, also known as lipid flipping, and the efficiency of fusion.

PMID- 25610721
TI  - TGN exit of the cation-independent mannose 6-phosphate receptor does not require
      acid hydrolase binding.
AB  - The cation-independent mannose 6-phosphate (Man-6-P) receptor (CI-MPR) binds
      newly synthesized, Man-6-P-containing lysosomal acid hydrolases in the trans
      Golgi network (TGN) for clathrin-mediated transport to endosomes. It has remained
      unresolved, however, whether acid hydrolase binding is required for exit of the
      CI-MPR from the TGN. To address this question we used a B cell line derived from
      a Mucolipidosis type II (MLII)/I-cell disease patient. In MLII patients, acid
      hydrolases do not acquire the Man-6-P recognition marker and as a consequence do
      not bind to the CI-MPR. This causes secretion of the majority of the acid
      hydrolases and a decreased lysosomal activity resulting in typical inclusion
      bodies. In agreement herewith, ultrastructural analysis of the MLII patient
      derived B cells showed numerous inclusion bodies with undigested material, which
      we defined as autolysosomes. By quantitative immuno-electron microscopy we then
      studied the distribution of the CI-MPR in these cells. We found that the level of
      co-localization of TGN-localized CI-MPR and clathrin was similar in MLII and
      control B cells. Moreover, the CI-MPR was readily found in endosomes of MLII
      cells and the TGN-to-early endosome ratio of CI-MPR labeling was unaltered. These
      data show that there is no block in TGN exit of the CI-MPR in the absence of Man
      6-P-modified acid hydrolases. Notably, late endosomes and inclusion bodies in
      MLII B cells contained increased levels of the CI-MPR, which likely reflects the
      reduced degradative capacity of these compartments.

PMID- 25610723
TI  - "Closing the loop" in cervical dystonia: a new clinical phenomenon.
AB  - BACKGROUND: The sensory trick or geste antagoniste is a cardinal feature of
      cervical dystonia. Patients are often aware of their tricks, using them to their
      advantage to temporarily improve dystonic symptoms. The typical sensory trick
      must be internally generated by the patient in order to be effective, and
      external mechanical pressure alone may not be sufficient. METHODS: We present a
      case description. We present and demonstrate a new clinical phenomenon in
      patients with cervical dystonia, which we call "closing the loop". DISCUSSION: We
      discuss the possible mechanisms underlying this finding.

PMID- 25610722
TI  - Ypt/Rab GTPases regulate two intersections of the secretory and the
      endosomal/lysosomal pathways.
AB  - A prevailing question in the Ypt/Rab field is whether these conserved GTPases are
      specific to cellular compartments. The established role for Ypt1 and its human
      homolog Rab1 is in endoplasmic reticulum (ER)-to-Golgi transport. More recently
      these regulators were implicated also in autophagy. Two different TRAPP
      complexes, I and III, were identified as the guanine-nucleotide-exchange factors
      (GEFs) of Ypt1 in ER-to-Golgi transport and autophagy, respectively. Confusingly,
      Ypt1 and TRAPP III were also suggested to regulate endosome-to-Golgi transport,
      implying that they function at multiple cellular compartments, and bringing into
      question the nature of Ypt/Rab specificity. Recently, we showed that the role of
      TRAPP III and Ypt1 in autophagy occurs at the ER and that they do not regulate
      endosome-to-Golgi transport. Here, we discuss the significance of this conclusion
      to the idea that Ypt/Rabs are specific to cellular compartments. We postulate
      that Ypt1 regulates 2 alternative routes emanating from the ER toward the Golgi
      and the lysosome/vacuole. We further propose that the secretory and
      endocytic/lysosomal pathways intersect in 2 junctures, and 2 Ypts, Ypt1 and
      Ypt31, coordinate transport in the 2 intersections: Ypt1 links ER-to-Golgi and ER
      to-autophagy transport, whereas Ypt31 links Golgi-to-plasma membrane (PM)
      transport with PM-to-Golgi recycling through endosomes.

PMID- 25610724
TI  - CD137 stimulation enhances the vaccinal effect of anti-tumor antibodies.
AB  - Some evidence suggests that monoclonal antibodies (mAb) can induce an adaptive
      immune response against tumor cells ("vaccinal effect"). Recently, we have shown
      that an anti-CD137 mAb can enhance the "vaccinal effect" of an anti-tumor mAb
      (cetuximab), thereby transforming a passive, monoclonal, short-term immunotherapy
      into an active, polyclonal, long-lasting immune response.

PMID- 25610725
TI  - Lenalidomide induces degradation of IKZF1 and IKZF3.
AB  - Lenalidomide and its analogs, thalidomide and pomalidomide, specifically inhibit
      growth of mature B-cell lymphomas, including multiple myeloma, and induce
      interleukin-2 (IL-2) release from T cells. We recently found that this results
      from activation of the CRBN-CRL4 E3 ubiquitin ligase to degrade the lymphoid
      transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos).

PMID- 25610726
TI  - An autophagy-dependent anticancer immune response determines the efficacy of
      melanoma chemotherapy.
AB  - There is ample experimental and clinical evidence that chemotherapies are more
      efficient if they succeed in (re)activating immune surveillance, hence triggering
      a long-term immune response against residual tumor cells. Most of the preclinical
      evidence supporting this notion has been obtained with transplantable cancers,
      for which it has been shown that chemotherapy-induced autophagy in cancer cells
      is mandatory for the recruitment of myeloid cells into the tumor bed and the
      subsequent T lymphocyte-mediated reduction in tumor growth. Here, we
      characterized the chemotherapeutic response of melanomas caused by 4-hydroxy
      tamoxifen-induced expression of the Cre recombinase in melanocytes that results
      in the activation of oncogenic Braf together with the inactivation of the tumor
      suppressor Pten, as well as the optional inactivation of the essential autophagy
      gene Atg7. Systemic chemotherapy with the anthracycline Mitoxantrone (MTX)
      reduced the growth of autophagy-competent melanomas (genotype: BrafCa/+;
      Ptenfl/fl; Atg7+/+), yet failed to affect the progression of autophagy-deficient
      melanomas (genotype: BrafCa/+; Ptenfl/fl; Atg7fl/fl). The growth-inhibitory
      effect of MTX on autophagy-competent melanomas was abolished by the combined
      depletion of CD4+ or CD8+ T lymphocytes. In conclusion, it appears that the
      success of chemotherapy against "spontaneous," genetically induced cancers is
      governed by the same rules as those applicable to transplantable tumors.

PMID- 25610727
TI  - Leveraging chemotherapy-induced lymphopenia to potentiate cancer immunotherapy.
AB  - First-line chemotherapy to combat primary malignant brain cancer is often
      accompanied by lymphopenic immunologic deficiency. Although counterintuitive,
      chemotherapy-induced lymphopenia can provide excellent host conditioning that may
      actually be leveraged to potentiate antitumor immunotherapy. We discuss here our
      preclinical and clinical experiences applying immunotherapy against glioblastoma,
      the most common and lethal primary malignant brain tumor, as well as the use of
      immunotherapeutics in the setting of standard-of-care temozolomide chemotherapy.

PMID- 25610728
TI  - Transcriptional profiling of whole blood: a rich source of immune biomarkers in
      cancer.
AB  - Immunotherapy is at the forefront of cancer treatment, and biomarkers are
      urgently needed to predict patient response to therapy. Recently, we discovered a
      4-gene peripheral blood mRNA signature for prolonged survival in patients treated
      with tremelimumab. Peripheral blood mRNA is a readily accessible and under
      utilized source of clinically relevant biomarkers.

PMID- 25610729
TI  - Chimeric antigen receptor engineered T cells can eliminate brain tumors and
      initiate long-term protection against recurrence.
AB  - CAR therapy has shown promise in treating cancer, but at the cost of unexpected
      toxicity against normal tissues, not predicted by preclinical testing. We are
      working to generate more physiologically relevant models for preclinical CAR
      toxicity testing, and in doing so, have discovered that CAR therapy induces
      immunogenic cell death, with the potential for cures.

PMID- 25610731
TI  - The potential impact of mouse model selection in preclinical evaluation of cancer
      immunotherapy.
AB  - This commentary provides the authors' perspective on the article "Routes of
      delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in
      mice", published in PLoS ONE. It also discusses the caveats of using subcutaneous
      tumors to model the treatment of human cancers versus orthotopic mouse models
      that more closely mimic human disease.

PMID- 25610730
TI  - In situ loading of skin dendritic cells with apoptotic bleb-derived antigens for
      the induction of tumor-directed immunity.
AB  - The generation and loading of dendritic cells (DC) ex-vivo for tumor vaccination
      purposes is laborious and costly. Direct intradermal (i.d.) administration of
      tumor-associated antigens could be an attractive alternative approach, provided
      that efficient uptake and cross-presentation by appropriately activated skin DCs
      can be achieved. Here, we compare the efficiency of i.d. delivery of relatively
      small apoptotic blebs (diameter ~0.1-1 MUm) derived from MART-1 transduced acute
      myeloid leukemia (AML) HL60 cells, to that of larger apoptotic cell remnants
      (ACR; 2-10 MUm) in a physiologically highly relevant human skin explant model.
      Injection of either fluorescently-labelled ACRs or blebs alone did not affect the
      number or distribution of migrated DC subsets from skin biopsies after 48 hours,
      but resulted in a general up-regulation of the co-stimulatory molecules CD83 and
      CD86 on skin DCs that had ingested apoptotic material. We have previously shown
      that i.d. administration of GM-CSF and IL-4 resulted in preferential migration of
      a mature and highly T cell-stimulatory CD11hiCD1a+CD14- dermal DC subset. Here,
      we found that co-injection of GM-CSF and IL-4 together with either ACRs or blebs
      resulted in uptake efficiencies within this dermal DC subset of 7.6% (+/-6.1%)
      and 19.1% (+/-15.9%), respectively, thus revealing a significantly higher uptake
      frequency of blebs (P < 0.02). Intradermal delivery of tumor-derived blebs did
      not affect the T-cell priming and TH-skewing abilities of migratory skin DC.
      Nevertheless, in contrast to i.d. administration of ACR, the injection of blebs
      lead to effective cross-presentation of MART-1 to specific CD8+ effector T cells.
      We conclude that apoptotic bleb-based vaccines delivered through the skin may
      offer an attractive, and broadly applicable, cancer immunotherapy.

PMID- 25610732
TI  - The kinase inhibitors dabrafenib and trametinib affect isolated immune cell
      populations.
AB  - Metastatic melanoma is frequently fatal. Optimal treatment regimens require both
      rapid and durable disease control, likely best achieved by combining targeted
      agents with immunotherapeutics. In order to accomplish this, a detailed
      understanding of the immune consequences of the kinase inhibitors used to treat
      melanoma is required.

PMID- 25610733
TI  - M1 and M2: there is no "good" and "bad"-How macrophages promote malignancy
      associated features in tumorigenesis.
AB  - We recently identified tumor-associated macrophages from pancreatic ductal
      adenocarcinoma sharing pro- and anti-inflammatory characteristics. Already in
      residence in the setting of chronic pancreatitis, local macrophages confer
      malignancy-associated features to premalignant pancreatic ductal epithelial cells
      by both promoting and inhibiting inflammation, either of which can foster
      malignant conversion. Our findings support the concept that contrasting modes of
      inflammation can promote tumorigenesis.

PMID- 25610734
TI  - Immune-mediated tumor evolution: Nanog links the emergence of a stem like cancer
      cell state and immune evasion.
AB  - Tumor cells undergo molecular evolution under immune pressure. Using a murine
      metastatic lung cancer model, we recently reported that evolutionary pressure
      enforced through vaccination incites gain of Nanog, a master transcription factor
      that mediates both emergence of a stem-like cancer cell state and immune evasion.
      Thus, therapeutic strategies aiming to blunt NANOG's expression in patient tumors
      may improve the clinical management of cancer.

PMID- 25610735
TI  - COMMD1 regulates inflammation and colitis-associated cancer progression.
AB  - NF-kappaB is a master transcriptional regulator of inflammation that plays an
      important role in oncogenesis, particularly in tumors that arise in the context
      of inflammation. Copper metabolism MURR1 domain-containing 1 (COMMD1) is a
      negative regulator of NF-kappaB. Recent genetic-based studies in both mice and
      human patients indicate that COMMD1 has an important role in controlling
      intestinal inflammation and constraining progression to colitis-associated
      cancer.

PMID- 25610736
TI  - Two in one: improving synthetic long peptide vaccines by combining antigen and
      adjuvant in one molecule.
AB  - Aiming to increase the potency of synthetic long peptide (SLP)-based cancer
      vaccines, the Toll-like receptor 2 (TLR2) ligand Pam3CSK4 was conjugated in a
      chemically defined fashion to SLPs harbouring both cytotoxic T lymphocyte (CTL)
      and T helper epitopes. We recently showed that these SLP-conjugates induce strong
      antitumor immunity in murine cancer models.

PMID- 25610738
TI  - Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.
AB  - Type I interferon inducers may potentially be engineered to function as antiviral
      and anticancer agents, or alternatively, vaccine adjuvants, all of which may have
      clinical applications. We recently described a simple strategy to convert a Toll
      like receptor 9 (TLR9) agonist devoid of interferon alpha (IFNalpha) stimulating
      activity into a robust Type I interferon inducer with potent vaccine adjuvant
      activity.

PMID- 25610737
TI  - Human polymorphonuclear neutrophils specifically recognize and kill cancerous
      cells.
AB  - Polymorphonuclear neutrophils (PMNs), the main effectors of the innate immune
      system, have rarely been considered as an anticancer therapeutic tool. However,
      recent investigations using animal models and preliminary clinical studies have
      highlighted the potential antitumor efficacy of PMNs. In the current study, we
      find that PMNs from some healthy donors naturally have potent cancer-killing
      activity against 4 different human cancer cell lines. The killing activity
      appears to be cancer cell-specific since PMNs did not kill primary normal
      epithelial cells or an immortalized breast epithelial cell line. Transfecting the
      immortalized mammary cells with plasmids expressing activated forms of the rat
      sarcoma viral oncogene homolog (Ras) and teratocarcinoma oncogene 21 (TC21)
      oncogenes was sufficient to provoke aggressive attack by PMNs. However,
      transfection with activated Ras-related C3 botulinum toxin substrate (Rac1) was
      ineffective, suggesting specificity in PMN-targeting of neoplastic cells.
      Furthermore, PMNs from lung cancer patients were also found to exhibit relatively
      poor cancer-killing activity compared to the cytolytic activity of the average
      healthy donor. Taken together, our results suggest that PMN-based treatment
      regimens may represent a paradigm shift in cancer immunotherapy that may be
      easily introduced into the clinic to benefit a subset of patients with PMN
      vulnerable tumors.

PMID- 25610739
TI  - Breaking through the central tolerance ceiling to unleash anticancer immune
      responses.
AB  - Central thymic tolerance mechanisms create a formidable barrier against the
      generation of self-reactive T cells. While preventing autoimmunity, this barrier
      also limits an effective antitumor immunological response. We recently reported
      that anti-RANKL blocking antibody breaches this central tolerance barrier, thus
      increasing the repertoire of melanoma reactive T cells. Thus, central tolerance
      blockade may be an effective therapeutic strategy to enhance anticancer immunity.

PMID- 25610740
TI  - The pancreatic cancer microenvironment: an immunologic battleground.
AB  - Recent studies of human pancreatic cancer challenge the mouse model-derived
      notion that the pancreas is a site of immune privilege. A heavy infiltration of
      CD8+ T cells expressing programmed cell death 1 (PD-1) and smaller numbers of
      myeloid cells and regulatory T cells provides rationale for the clinical
      evaluation of immune checkpoint inhibition as a pancreatic cancer therapeutic
      strategy.

PMID- 25610742
TI  - Targeting Galectin-1 in pancreatic cancer: immune surveillance on guard.
AB  - The tumor microenviroment and immune barrier are known to modulate malignant
      disease progression. We have recently identified Galectin-1 as a key player in a
      novel stromal regulatory reaction driving immune evasion in pancreatic tumors in
      vivo. These results suggest that Galectin-1 inhibition represents a potential
      therapeutic strategy for one of the most deadly types of cancer.

PMID- 25610741
TI  - NK cells and T cells cooperate during the clinical course of colorectal cancer.
AB  - Recent evidence suggests that natural killer (NK) cells are typically defective
      in infiltrating solid tumors, with the exception of gastrointestinal stromal
      tumors (GIST). Interestingly, however, infrequently infiltrating NK cells do not
      appear to have a direct effect on tumor progression. Here, prompted by the recent
      evidence that NK cell and T cell crosstalk may trigger, or enhance, tumor antigen
      specific immune responses, we have tested the clinical significance of this
      reciprocal signaling. To this end, a tissue microarray constructed with 1410
      colorectal carcinoma (CRC) patient specimens was stained with NK and T cell
      antigen-specific monoclonal antibodies, utilizing the immunoperoxidase staining
      technique. Cut-off scores for positive (>4 NK cells) and negative (<=4 NK cells)
      NK cell CRC patient samples were determined using receiver operating
      characteristic curve analysis. Using this approach, NK cells were detected in 423
      (30%) of the 1410 CRC specimens evaluated. The number of NK cells was >4 in only
      132 (9%) of CRC samples. Correlation of the immunohistochemical staining results
      together with analysis of the clinical course of the disease revealed that the
      infiltration of colorectal tumors with both NK cells and CD8+ T cells is
      associated with prolonged patient survival. In contrast, infiltration of tumors
      with NK cells in combination with CD3+ and CD4+ T lymphocytes had no detectable
      effect on the clinical course of the disease. These results suggest that NK cell
      and CD8+ T cell crosstalk in the tumor microenvironment may benefit patient
      outcome and further, that the enumeration of infiltrating NK and CD8+ T cells in
      CRC tumors may provide useful prognostic information.

PMID- 25610743
TI  - Breaking the vicious cycle between breast cancer cells and tumor-associated
      macrophages.
AB  - We recently identified a vicious cycle between granulocyte macrophage colony
      stimulating factor (GM-CSF) arising from breast cancer cells that have undergone
      epithelial-mesenchymal transition (EMT) and the tumor-associated macrophage (TAM)
      derived chemokine CCL18, a signaling loop that promotes tumor metastasis. Tumor
      derived lactate skews GM-CSF-activated macrophages to an anti-inflammatory and
      immunosuppressive M2 phenotype, suggesting that breaking this cycle in
      combination with glycolysis inhibitors may inhibit tumor development.

PMID- 25610744
TI  - Innate gammadeltaT17 cells convert cancer-elicited inflammation into
      immunosuppression through myeloid-derived suppressor cells.
AB  - Chronic inflammation has been linked to cancer development and metastasis. We
      have recently demonstrated that gammadelta T cells are the major cellular source
      of IL-17 (gammadeltaT17) and accumulation of gammadeltaT17 cells correlates with
      human colorectal cancer progression through recruitment and expansion of myeloid
      derived suppressor cells, thus converting tumor-elicited inflammation into
      immunosuppression.

PMID- 25610745
TI  - Cancer chemotherapy agents target intratumoral dendritic cells to potentiate
      antitumor immunity.
AB  - Cytotoxic drugs capable of killing cancer cells in conjunction with targeted
      conversion of tumor resident, tolerogenic dendritic cells (DCs) into efficient
      antigen presenting cells (APCs) are highly complementary therapeutic routes to
      boost antitumor immunity. Our data suggest that the microtubule-depolymerizing
      compounds Dolastatin 10 and Ansamitocin P3 may serve as prototypes for a class of
      agents that display this binary mode of action.

PMID- 25610746
TI  - Targeting programmed cell death ligand 1 in osteosarcoma: an auto-commentary on
      therapeutic potential.
AB  - Programmed cell death ligand 1 (PDL1) expression was recently shown to correlate
      with tumor-infiltrating lymphocytes (TILs) in a subset of osteosarcoma patients.
      Among clinical factors evaluated across human osteosarcoma samples, a pulmonary
      origin of metastases correlated with high PDL1 expression and prominent TILs.
      Considering that multiple agents targeting PD-1/PDL1 are under development,
      targeting this immune checkpoint may be a novel immunotherapeutic route for
      osteosarcoma in future clinical trials.

PMID- 25610747
TI  - Chemotherapy-induced myeloid suppressor cells and antitumor immunity: The Janus
      face of chemotherapy in immunomodulation.
AB  - Tumor recurrence remains a major problem for patients with cancer, even after
      initial beneficial responses to standard-of-care chemotherapeutic agents. With
      the recent advances in immunotherapy strategies, there is growing interest in
      synergistically combining immunotherapy with conventional chemotherapy to achieve
      durable antitumor effects. In some cases, chemotherapy-induced myeloid suppressor
      cells represent a critical obstacle to achieving this goal.

PMID- 25610748
TI  - Multifaceted antitumor responses to activating anti-CD40 antibody therapy
      combined with immunomodulatory or targeted agents.
AB  - Therapeutic targeting of the CD40 pathway may be efficacious for cancer
      treatment. Accumulating evidence suggests synergistic and unique antitumor
      responses may be achieved using CD40-based therapies in combination with other
      immunomodulators or targeted agents.

PMID- 25610749
TI  - Late development of splenic sarcoidosis-like lesions in a patient with metastatic
      melanoma and long-lasting clinical response to ipilimumab.
AB  - A male patient with Stage IV melanoma was treated with ipilimumab resulting in a
      long-lasting partial response according to RECIST criteria. However, twenty
      months after ipilimumab treatment, routine follow-up CT scan revealed new splenic
      lesions initially interpreted as indicative of progressive disease. Nevertheless,
      a biopsy was performed and histologic evaluation showed that the lesions did not
      contain malignant cells but rather constituted non-caseating epithelioid cell
      granulomas consistent with sarcoidosis. As the patient was asymptomatic no
      treatment was initiated and over the following months the splenic lesions slowly
      disappeared and to date the patient remains in remission. Ipilimumab is now
      widely used in the treatment of melanoma patients. Our case-report illustrates
      that physicians should consider the possibility of ipilimumab induced visceral
      sarcoidosis-like reactions, mimicking metastatic lesions, developing even many
      months after ipilimumab treatment. Thus, biopsy of such suspicious lesions is
      advisable to avoid misinterpretation as disease progression and unnecessary
      resumption of cancer therapy.

PMID- 25610750
TI  - Recent advances and new opportunities for targeting human dendritic cells in
      situ.
AB  - Targeting antigens directly to dendritic cells (DCs) in situ has emerged as a
      promising strategy to potentiate immunity. A recent clinical trial of antibody
      mediated targeting of tumor antigen NY-ESO1 to the DC receptor DEC-205
      demonstrated an induction of strong cellular and humoral responses. Recent
      studies with DC-targeting via nanoparticles suggest that combinatorial targeting
      of multiple human DC subsets may further improve the efficacy of DC targeting.

PMID- 25610751
TI  - New insights into the mechanism of action of immune checkpoint antibodies.
AB  - Preclinical models have been developed and applied to predict the clinical
      efficacy of immune checkpoint antibodies. Now these models can be used to dissect
      the mechanisms by which such immunotherapeutic antibodies work and to build the
      rationale for combining immune checkpoint-targeting antibodies with potential
      synergistic activity in cancer patients.

PMID- 25610752
TI  - Rhodiola rosea therapy for major depressive disorder: a study protocol for a
      randomized, double-blind, placebo- controlled trial.
AB  - BACKGROUND: Rhodiola rosea (R. rosea), a botanical of both western and
      traditional Chinese medicine, has been used as a folk remedy for improving
      stamina and reducing stress. However, few controlled clinical trials have
      examined the safety and efficacy of R. rosea for the treatment of major
      depressive disorder (MDD). This study seeks to evaluate the safety and efficacy
      of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel
      group study design. METHODS / DESIGN: Subjects with MDD not receiving
      antidepressant therapy will be randomized to either R. rosea extract 340-1,360 mg
      daily; sertraline 50-200 mg daily, or placebo for 12 weeks. The primary outcome
      measure will be change over time in the mean 17-item Hamilton Depression Rating
      score. Secondary outcome measures will include safety and quality of life
      ratings. Statistical procedures will include mixed-effects models to assess
      efficacy for primary and secondary outcomes. DISCUSSION: This study will provide
      valuable preliminary information on the safety and efficacy data of R. rosea
      versus conventional antidepressant therapy of MDD. It will also inform additional
      hypotheses and study design of future, fully powered, phase III clinical trials
      with R. rosea to determine its safety and efficacy in MDD.

PMID- 25610753
TI  - Arp2/3 complex function in the epidermis.
AB  - An exciting frontier in biology is understanding the functions of basic cell
      biological machinery in complex tissues. This approach is expected to uncover
      novel modes of regulation as well as reveal how core machinery is repurposed by
      different tissues to accomplish different physiological outputs. F-actin plays
      roles in cell shape, adhesion, migration and signaling - diverse functions that
      require a specific organization established by a myriad of regulators. Here, we
      discuss the role of the actin nucleating Arp2/3 complex and the unexpected roles
      that it plays in a stratified epithelial tissue, the epidermis. While many
      expected phenotypes such as defects in architecture and cell adhesion were
      lacking, loss of the Arp2/3 complex activity resulted in epidermal barrier and
      differentiation defects. This teaches us that, while informative, cell culture
      approaches are limiting and that studies of the Arp2/3 complex in diverse tissues
      are expected to yield many more surprises. 

PMID- 25610754
TI  - MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial
      barrier functions.
AB  - Tightly controlled epithelial and endothelial barriers are a prerequisite for
      life as these barriers separate multicellular organisms from their environment
      and serve as first lines of defense. Barriers between neighboring epithelial
      cells are formed by multiple intercellular junctions including the 'apical
      junctional complex-AJC' with tight junctions (TJ), adherens junctions (AJ), and
      desmosomes. TJ consist of tetraspan transmembrane proteins like occludin, various
      claudins that directly control paracellular permeability, and the 'Junctional
      Adhesion Molecules' (JAMs). For establishing tight barriers TJ are essential but
      at the same time have to allow also selective permeability. For this, TJ need to
      be tightly regulated and controlled. This is organized by a variety of adaptor
      molecules, i.e., protein kinases, phosphatases and GTPases, which in turn are
      regulated and fine-tuned involving microRNAs (miRNAs). In this review we
      summarize available data on the role and targeting of miRNAs in the maintenance
      of epithelial and/or endothelial barriers. 

PMID- 25610756
TI  - Claudin-7, -16, and -19 during mouse kidney development.
AB  - Members of the claudin family of tight junction proteins are critical for
      establishing epithelial barriers and for the regulation of paracellular
      transport. To understand their roles during kidney development, we first
      performed RT-PCR analyses and determined that 23 claudin family members were
      expressed in embryonic day (E) 13.5 mouse kidneys. Based on their developmental
      expression and phenotypes in mouse models, we hypothesized that 3 claudin members
      could affect nephron formation during kidney development. Using whole mount in
      situ hybridization and immunohistochemistry, we demonstrated that Claudin-7
      (Cldn7) was expressed in the nephric duct, the emerging ureteric bud, and in
      tubules derived from ureteric bud branching morphogenesis. In contrast, Claudin
      16 (Cldn16) and Claudin-19 (Cldn19) were expressed at later stages of kidney
      development in immature renal tubules that become the Loop of Henle. To determine
      if a loss of these claudins would perturb kidney development, we examined newborn
      kidneys from mutant mouse models lacking Cldn7 or Cldn16. In both models, we
      noted no evidence for any congenital renal malformation and quantification of
      nephron number did not reveal a decrease in nephron number when compared to
      wildtype littermates. In summary, Cldn7, Cldn16, and Cldn19 are expressed in
      different epithelial lineages during kidney development. Mice lacking Cldn7 or
      Cldn16 do not have defects in de novo nephron formation, and this suggests that
      these claudins primarily function to regulate paracellular transport in the
      mature nephron. 

PMID- 25610757
TI  - Loss of E-cadherin and epithelial to mesenchymal transition is not required for
      cell motility in tissues or for metastasis.
AB  - Loss of E-cadherin has been long considered to be a major hallmark of epithelial
      mesenchymal transition (EMT) and has been reported in various cancers. P120
      catenin regulates E-cadherin stability on the cell surface and also plays a role
      in intracellular signaling by modulating nuclear transcription. We recently
      characterized the nature of interactions between p120 catenin and Mucin 1 (MUC1)
      in pancreatic cancer. Expression of different p120 catenin isoforms with and
      without MUC1 induced distinct morphologies, cell adhesion, and dynamic properties
      of motility along with different metastatic properties in vivo. Re-expression of
      p120 catenin isoform 3A in the context of MUC1 expression in a p120 catenin
      deficient cell line stabilized expression of E-cadherin. However, orthotopic
      implantation of tumors using this stable cell line produced large metastatic
      lesions to the liver, which exceeded the volume of the primary tumor, suggesting
      down regulation of E-cadherin is not required for tumor metastasis. Here we
      extend those studies by showing that ectopic expression of E-cadherin does not
      block in vitro invasion of the pancreatic cancer cells, and instead accelerated
      the rate of tumor invasion. Furthermore, results from 23 cases of human
      pancreatic primary tumor specimens revealed that most tumors exhibiting
      metastatic activity retained epithelial morphology and E-cadherin gene
      expression. Our results indicate that loss of E-cadherin and EMT are not required
      for metastasis and that an epithelial morphology can be maintained during the
      process of tumor cell movement. 

PMID- 25610755
TI  - Pathogen-inspired drug delivery to the central nervous system.
AB  - For as long as the human blood-brain barrier (BBB) has been evolving to exclude
      bloodborne agents from the central nervous system (CNS), pathogens have adopted a
      multitude of strategies to bypass it. Some pathogens, notably viruses and certain
      bacteria, enter the CNS in whole form, achieving direct physical passage through
      endothelial or neuronal cells to infect the brain. Other pathogens, including
      bacteria and multicellular eukaryotic organisms, secrete toxins that
      preferentially interact with specific cell types to exert a broad range of
      biological effects on peripheral and central neurons. In this review, we will
      discuss the directed mechanisms that viruses, bacteria, and the toxins secreted
      by higher order organisms use to enter the CNS. Our goal is to identify ligand
      mediated strategies that could be used to improve the brain-specific delivery of
      engineered nanocarriers, including polymers, lipids, biologically sourced
      materials, and imaging agents. 

PMID- 25610758
TI  - Connecting metabolism to intestinal barrier function: The role of leptin.
AB  - Structure and function of the intestinal epithelial barrier (IEB) are dependent
      upon the integrity of junctional protein structures sealing the apical surface
      between epithelial cells. Tight junctions (TJ) and the surrounding apical F-actin
      cytoskeleton are involved in the regulation of paracellular permeability. The
      regulation of actin cytoskeleton organization by RhoA/Rho-kinase (ROCK) pathway
      plays an important role in TJ assembly and function. There is mounting evidence
      that the adipocyte-derived hormone leptin exerts pleiotropic effects on the
      intestinal epithelium including nutrient absorption, epithelial growth,
      inflammation and injury. Leptin activates multiple cell signaling pathways in
      intestinal epithelial cells (IEC) that can explain these pleiotropic effects.
      However, these pathways are also involved in the primary role of leptin that is
      the regulation of energy and glucose metabolism homeostasis. In this commentary,
      we examine how the interplay between leptin signaling pathways that regulate cell
      metabolism could impact upon IEB function. 

PMID- 25610759
TI  - The phosphoinositide-binding protein TRAF4 modulates tight junction stability and
      migration of cancer cells.
AB  - Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4), a protein
      localized in TJs in normal epithelial cells, is frequently overexpressed in
      carcinomas. We recently found that TRAF4 impedes TJ formation/stability and
      favors cell migration, 2 hallmarks of cancer progression. In addition TRAF4
      contributes to the TGF-beta-induced epithelial-mesenchymal transition (EMT),
      metastasis, and p53 destabilization. TRAF4 recruitment to TJs is a prerequisite
      for its biological function on TJ formation/stability and on cell migration.
      Interestingly, TRAF4 is targeted to TJs through lipid-binding. The trimeric TRAF
      domain of TRAF4 binds 3 phosphoinositide (PIP) molecules. These findings shed new
      light on the role of TRAF4 in cancer progression; they provide a novel link
      between lipid metabolism and cancer progression and support the notion that TRAF4
      could be a relevant target for cancer therapies. TRAF4 belongs to a family of 7
      human proteins involved in different biological processes, such as inflammation,
      immunity and embryonic development. While the lipid-binding ability of the TRAF
      domain is conserved among the whole TRAF protein family, its functional role
      remains to be established for the remaining TRAF proteins. 

PMID- 25610760
TI  - Imaging of repeated episodes of demyelination and remyelination in multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is characterized by the formation of demyelinating
      lesions in the white matter (WM). However, the timecourse of the evolution of
      healthy white matter into fully demyelinated lesions in MS is not well
      understood. We use a recently proposed technique to examine magnetization
      transfer ratio (MTR) timecourses in lesions segmented from MTR images in patients
      with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS). In both
      groups we found MTR lesions forming both in previously normal appearing WM (de
      novo lesions) as well as in previously lesional tissue that appears to be
      experiencing a second round of inflammatory demyelination (repeat lesions). Both
      de novo and repeat lesions exhibited significant, but incomplete MTR recovery,
      suggesting partial remyelination; post-lesion MTR values in de novo lesions were
      similar to pre-lesion values in repeat lesions. Both de novo and repeat lesions
      were found in subjects in relapsing-remitting and secondary progressive stages of
      MS, and repeat lesions appeared relatively more common in the secondary
      progressive phase. These observations support the hypothesis that entirely
      demyelinated lesions found on histopathology are the result of multiple episodes
      of demyelination and incomplete remyelination, and may have implications for MS
      treatment development efforts aimed at neuroprotection and enhancing
      remyelination. 

PMID- 25610761
TI  - Increased cortical curvature reflects white matter atrophy in individual patients
      with early multiple sclerosis.
AB  - OBJECTIVE: White matter atrophy occurs independently of lesions in multiple
      sclerosis. In contrast to lesion detection, the quantitative assessment of white
      matter atrophy in individual patients has been regarded as a major challenge. We
      therefore tested the hypothesis that white matter atrophy (WMA) is present at the
      very beginning of multiple sclerosis (MS) and in virtually each individual
      patient. To find a new sensitive and robust marker for WMA we investigated the
      relationship between cortical surface area, white matter volume (WMV), and whole
      brain-surface-averaged rectified cortical extrinsic curvature. Based on
      geometrical considerations we hypothesized that cortical curvature increases if
      WMV decreases and the cortical surface area remains constant. METHODS: In total,
      95 participants were enrolled: 30 patients with early and advanced relapsing
      remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's
      disease (AD) and 5 patients with clinically isolated syndrome (CIS). RESULTS:
      29/30 MS and 5/5 CIS patients showed lower WMV than expected from their
      intracranial volume (average reduction 13.0%, P < 10(- 10)), while the cortical
      surface area showed no significant differences compared with controls. The
      estimated WMV reductions were correlated with an increase in cortical curvature
      (R = 0.62, P = 0.000001). Discriminant analysis revealed that the curvature
      increase was highly specific for the MS and CIS groups (96.7% correct assignments
      between MS and control groups) and was significantly correlated with reduction of
      white matter fractional anisotropy, as determined by diffusion tensor imaging and
      the Expanded Disability Status Scale. As expected by the predominant gray and WM
      degeneration in AD, no systematic curvature increase was observed in AD.
      CONCLUSION: Whole-brain-averaged cortical extrinsic curvature appears to be a
      specific and quantitative marker for a WMV-cortex disproportionality and allows
      us to assess "pure" WMA without being confounded by intracranial volume. WMA
      seems to be a characteristic symptom in early MS and can already occur in
      patients with CIS and should thus be considered in future MS research and
      clinical studies.

PMID- 25610762
TI  - Neural correlates of transitive and intransitive action imitation: an
      investigation using voxel-based morphometry.
AB  - The ability to reproduce visually presented actions has been studied through
      neuropsychological observations of patients with ideomotor apraxia. These studies
      include attempts to understand the neural basis of action reproduction based on
      lesion-symptom mapping in different patient groups. While there is a convergence
      of evidence that areas in the parietal and frontal lobes within the left
      hemisphere are involved in the imitation of a variety of actions, questions
      remain about whether the results generalize beyond the imitation of tool use and
      whether the presence of a strong grasp component of the action is critical. Here
      we used voxel-based lesion-symptom mapping to assess the neural substrates of
      imitating meaningful (familiar, MF) and meaningless (unfamiliar, ML) tool-related
      (transitive) and non-tool related (intransitive) actions. The analysis showed
      that the left parietal cortex was involved in the imitation of transitive
      gestures, regardless of whether they were meaningful or not. In addition there
      was poor reproduction of meaningless actions (both transitive and intransitive)
      following damage of the right frontal cortex. These findings suggest a role of
      right frontal regions in processing of unfamiliar actions. 

PMID- 25610763
TI  - PTSD symptom severity is associated with increased recruitment of top-down
      attentional control in a trauma-exposed sample.
AB  - BACKGROUND: Recent neuroimaging work suggests that increased amygdala responses
      to emotional stimuli and dysfunction within regions mediating top down
      attentional control (dorsomedial frontal, lateral frontal and parietal cortices)
      may be associated with the emergence of anxiety disorders, including
      posttraumatic stress disorder (PTSD). This report examines amygdala
      responsiveness to emotional stimuli and the recruitment of top down attention
      systems as a function of task demands in a population of U.S. military service
      members who had recently returned from combat deployment in Afghanistan/Iraq.
      Given current interest in dimensional aspects of pathophysiology, it is
      worthwhile examining patients who, while not meeting full PTSD criteria, show
      clinically significant functional impairment. METHODS: Fifty-seven participants
      with sub-threshold levels of PTSD symptoms completed the affective Stroop task
      while undergoing fMRI. Participants with PTSD or depression at baseline were
      excluded. RESULTS: Greater PTSD symptom severity scores were associated with
      increased amygdala activation to emotional, particularly positive, stimuli
      relative to neutral stimuli. Furthermore, greater PTSD symptom severity was
      associated with increased superior/middle frontal cortex response during task
      conditions relative to passive viewing conditions. In addition, greater PTSD
      symptom severity scores were associated with: (i) increased activation in the
      dorsolateral prefrontal, lateral frontal, inferior parietal cortices and
      dorsomedial frontal cortex/dorsal anterior cingulate cortex (dmFC/dACC) in
      response to emotional relative to neutral stimuli; and (ii) increased functional
      connectivity during emotional trials, particularly positive trials, relative to
      neutral trials between the right amygdala and dmFC/dACC, left caudate/anterior
      insula cortex, right lentiform nucleus/caudate, bilateral inferior parietal
      cortex and left middle temporal cortex. CONCLUSIONS: We suggest that these data
      may reflect two phenomena associated with increased PTSD symptomatology in combat
      exposed, but PTSD negative, armed services members. First, these data indicate
      increased emotional responsiveness by: (i) the positive relationship between PTSD
      symptom severity and amygdala responsiveness to emotional relative to neutral
      stimuli; (ii) greater BOLD response as a function of PTSD symptom severity in
      regions implicated in emotion (striatum) and representation (occipital and
      temporal cortices) during emotional relative to neutral conditions; and (iii)
      increased connectivity between the amygdala and regions implicated in emotion
      (insula/caudate) and representation (middle temporal cortex) as a function of
      PTSD symptom severity during emotional relative to neutral trials. Second, these
      data indicate a greater need for the recruitment of regions implicated in top
      down attention as indicated by (i) greater BOLD response in superior/middle
      frontal gyrus as a function of PTSD symptom severity in task relative to view
      conditions; (ii) greater BOLD response in dmFC/dACC, lateral frontal and inferior
      parietal cortices as a function of PTSD symptom severity in emotional relative to
      neutral conditions and (iii) greater functional connectivity between the amygdala
      and inferior parietal cortex as a function of PTSD symptom severity during
      emotional relative to neutral conditions.

PMID- 25610764
TI  - The relationship between regional microstructural abnormalities of the corpus
      callosum and physical and cognitive disability in relapsing-remitting multiple
      sclerosis.
AB  - Significant corpus callosum (CC) involvement has been found in relapsing
      remitting multiple sclerosis (RRMS), even if conventional magnetic resonance
      imaging measures have shown poor correlation with clinical disability measures.
      In this work, we tested the potential of multimodal imaging of the entire CC to
      explain physical and cognitive disability in 47 patients with RRMS. Values of
      thickness, fractional anisotropy (FA) and mean diffusivity (MD) were extracted
      from 50 regions of interest (ROIs) sampled along the bundle. The relationships
      between clinical, neuropsychological and imaging variables were assessed by using
      Spearman's correlation. Multiple linear regression analysis was employed in order
      to identify the relative importance of imaging metrics in modeling different
      clinical variables. Regional fiber composition of the CC differentially explained
      the response variables (Expanded Disability Status Scale [EDSS], cognitive
      impairment). Increases in EDSS were explained by reductions in CC thickness and
      MD. Cognitive impairment was mainly explained by FA reductions in the genu and
      splenium. Regional CC imaging properties differentially explained disability
      within RRMS patients revealing strong, distinct patterns of correlation with
      clinical and cognitive status of patients affected by this specific clinical
      phenotype. 

PMID- 25610766
TI  - Subcortical brain segmentation of two dimensional T1-weighted data sets with
      FMRIB's Integrated Registration and Segmentation Tool (FIRST).
AB  - Brain atrophy has been identified as an important contributing factor to the
      development of disability in multiple sclerosis (MS). In this respect, more and
      more interest is focussing on the role of deep grey matter (DGM) areas. Novel
      data analysis pipelines are available for the automatic segmentation of DGM using
      three-dimensional (3D) MRI data. However, in clinical trials, often no such high
      resolution data are acquired and hence no conclusions regarding the impact of new
      treatments on DGM atrophy were possible so far. In this work, we used FMRIB's
      Integrated Registration and Segmentation Tool (FIRST) to evaluate the possibility
      of segmenting DGM structures using standard two-dimensional (2D) T1-weighted MRI.
      In a cohort of 70 MS patients, both 2D and 3D T1-weighted data were acquired. The
      thalamus, putamen, pallidum, nucleus accumbens, and caudate nucleus were
      bilaterally segmented using FIRST. Volumes were calculated for each structure and
      for the sum of basal ganglia (BG) as well as for the total DGM. The accuracy and
      reliability of the 2D data segmentation were compared with the respective results
      of 3D segmentations using volume difference, volume overlap and intra-class
      correlation coefficients (ICCs). The mean differences for the individual
      substructures were between 1.3% (putamen) and -25.2% (nucleus accumbens). The
      respective values for the BG were -2.7% and for DGM 1.3%. Mean volume overlap was
      between 89.1% (thalamus) and 61.5% (nucleus accumbens); BG: 84.1%; DGM: 86.3%.
      Regarding ICC, all structures showed good agreement with the exception of the
      nucleus accumbens. The results of the segmentation were additionally validated
      through expert manual delineation of the caudate nucleus and putamen in a subset
      of the 3D data. In conclusion, we demonstrate that subcortical segmentation of 2D
      data are feasible using FIRST. The larger subcortical GM structures can be
      segmented with high consistency. This forms the basis for the application of
      FIRST in large 2D MRI data sets of clinical trials in order to determine the
      impact of therapeutic interventions on DGM atrophy in MS. 

PMID- 25610765
TI  - Volume of interest-based [18F]fluorodeoxyglucose PET discriminates MCI converting
      to Alzheimer's disease from healthy controls. A European Alzheimer's Disease
      Consortium (EADC) study.
AB  - An emerging issue in neuroimaging is to assess the diagnostic reliability of PET
      and its application in clinical practice. We aimed at assessing the accuracy of
      brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and
      healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects
      recruited in five centers of the European AD Consortium were enrolled. Group
      analysis was performed by SPM8 to confirm metabolic differences. Discriminant
      analyses were then carried out using the mean FDG uptake values normalized to the
      cerebellum computed in 45 anatomical volumes of interest (VOIs) in each
      hemisphere (90 VOIs) as defined in the Automated Anatomical Labeling (AAL) Atlas
      and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo
      functional characteristics. Further, asymmetry indexes were calculated for both
      datasets. Accuracy of discrimination by a Support Vector Machine and the AAL VOIs
      was tested against a validated method (PALZ). At the voxel level SMP8 showed a
      relative hypometabolism in the bilateral precuneus, and posterior cingulate,
      temporo-parietal and frontal cortices. Discriminant analysis classified subjects
      with an accuracy ranging between .91 and .83 as a function of data organization.
      The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry
      values reaching an area under the ROC curve of .947, significantly larger than
      the one obtained by the PALZ score. High accuracy in discriminating MCI
      converters from healthy controls was reached by a non-linear classifier based on
      SVM applied on predefined anatomo-functional regions and inter-hemispheric
      asymmetries. Data pre-processing was automated and simplified by an in-house
      created Matlab-based script encouraging its routine clinical use. Further
      validation toward nonconverter MCI patients with adequately long follow-up is
      needed. 

PMID- 25610767
TI  - Individual differences in symptom severity and behavior predict neural activation
      during face processing in adolescents with autism.
AB  - Despite the impressive literature describing atypical neural activation in
      visuoperceptual face processing regions in autism, almost nothing is known about
      whether these perturbations extend to more affective regions in the circuitry and
      whether they bear any relationship to symptom severity or atypical behavior.
      Using fMRI, we compared face-, object-, and house-related activation in
      adolescent males with high-functioning autism (HFA) and typically developing (TD)
      matched controls. HFA adolescents exhibited hypo-activation throughout the core
      visuoperceptual regions, particularly in the right hemisphere, as well as in some
      of the affective/motivational face-processing regions, including the posterior
      cingulate cortex and right anterior temporal lobe. Conclusions about the relative
      hyper- or hypo-activation of the amygdala depended on the nature of the contrast
      that was used to define the activation. Individual differences in symptom
      severity predicted the magnitude of face activation, particularly in the right
      fusiform gyrus. Also, among the HFA adolescents, face recognition performance
      predicted the magnitude of face activation in the right anterior temporal lobe, a
      region that supports face individuation in TD adults. Our findings reveal a
      systematic relation between the magnitude of neural dysfunction, severity of
      autism symptoms, and variation in face recognition behavior in adolescents with
      autism. In so doing, we uncover brain-behavior relations that underlie one of the
      most prominent social deficits in autism and help resolve discrepancies in the
      literature. 

PMID- 25610768
TI  - Connectivity supporting attention in children with attention deficit
      hyperactivity disorder.
AB  - Intra-subject variability (ISV) is the most consistent behavioral deficit in
      Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with
      networks involved in sustaining task control (cingulo-opercular network: CON) and
      self-reflective lapses of attention (default mode network: DMN). The current
      study examined whether connectivity supporting attentional control is atypical in
      children with ADHD. Group differences in full-brain connection strength and brain
      behavior associations with attentional control measures were examined for the
      late-developing CON and DMN in 50 children with ADHD and 50 typically-developing
      (TD) controls (ages 8-12 years). Children with ADHD had hyper-connectivity both
      within the CON and within the DMN. Full-brain behavioral associations were found
      for a number of between-network connections. Across both groups, more anti
      correlation between DMN and occipital cortex supported better attentional
      control. However, in the TD group, this brain-behavior association was stronger
      and occurred for a more extensive set of DMN-occipital connections. Differential
      support for attentional control between the two groups occurred with a number of
      CON-DMN connections. For all CON-DMN connections identified, increased between
      network anti-correlation was associated with better attentional control for the
      ADHD group, but worse attentional control in the TD group. A number of between
      network connections with the medial frontal cortex, in particular, showed this
      relationship. Follow-up analyses revealed that these associations were specific
      to attentional control and were not due to individual differences in working
      memory, IQ, motor control, age, or scan motion. While CON-DMN anti-correlation is
      associated with improved attention in ADHD, other circuitry supports improved
      attention in TD children. Greater CON-DMN anti-correlation supported better
      attentional control in children with ADHD, but worse attentional control in TD
      children. On the other hand, greater DMN-occipital anti-correlation supported
      better attentional control in TD children. 

PMID- 25610769
TI  - White matter integrity of premotor-motor connections is associated with motor
      output in chronic stroke patients.
AB  - Corticocortical functional interactions between the primary motor cortex (M1) and
      secondary motor areas, such as the dorsal (PMd) and ventral (PMv) premotor
      cortices and the supplementary motor area (SMA) are relevant for residual motor
      output after subcortical stroke. We hypothesized that the microstructural
      integrity of the underlying white matter tracts also plays a role in preserved
      motor output. Using diffusion-tensor imaging we aimed at (i) reconstructing
      individual probable intrahemispheric connections between M1 and the three
      secondary areas (PMd, PMv, SMA) and (ii) examining the extent to which the tract
      related microstructural integrity correlates with residual motor output. The
      microstructural integrity of the tract connecting ipsilesional M1 and PMd was
      significantly associated with motor output (R = 0.78, P = 0.02). The present
      results support the view that ipsilesional secondary motor areas such as the PMd
      might support M1 via corticocortical connections to generate motor output after
      stroke. 

PMID- 25610770
TI  - Multi-modal MRI of mild traumatic brain injury.
AB  - Multi-modal magnetic resonance imaging (MRI) that included high resolution
      structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio
      (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed
      in mild traumatic brain injury (mTBI) patients with negative computed tomographic
      scans and in an orthopedic-injured (OI) group without concomitant injury to the
      brain. The OI group served as a comparison group for mTBI. MRI scans were
      performed both in the acute phase of injury (~24 h) and at follow-up (~90 days).
      DTI data was analyzed using tract based spatial statistics (TBSS). Global and
      regional atrophies were calculated using tensor-based morphometry (TBM). MTR
      values were calculated using the standard method. MRSI was analyzed using LC
      Model. At the initial scan, the mean diffusivity (MD) was significantly higher in
      the mTBI cohort relative to the comparison group in several white matter (WM)
      regions that included internal capsule, external capsule, superior corona
      radiata, anterior corona radiata, posterior corona radiata, inferior fronto
      occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps
      minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal
      tract in the right hemisphere. TBSS analysis failed to detect significant
      differences in any DTI measures between the initial and follow-up scans either in
      the mTBI or OI group. No significant differences were found in MRSI, MTR or
      morphometry between the mTBI and OI cohorts either at the initial or follow-up
      scans with or without family wise error (FWE) correction. Our study suggests that
      a number of WM tracts are affected in mTBI in the acute phase of injury and that
      these changes disappear by 90 days. This study also suggests that none of the MRI
      modalities used in this study, with the exception of DTI, is sensitive in
      detecting changes in the acute phase of mTBI. 

PMID- 25610771
TI  - Hyperconnectivity in juvenile myoclonic epilepsy: a network analysis.
AB  - OBJECTIVE: Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic)
      generalized epilepsy (IGE) syndrome characterized by impairments in executive and
      cognitive control, affecting independent living and psychosocial functioning.
      There is a growing consensus that JME is associated with abnormal function of
      diffuse brain networks, typically affecting frontal and fronto-thalamic areas.
      METHODS: Using diffusion MRI and a graph theoretical analysis, we examined
      bivariate (network-based statistic) and multivariate (global and local)
      properties of structural brain networks in patients with JME (N = 34) and matched
      controls. Neuropsychological assessment was performed in a subgroup of 14
      patients. RESULTS: Neuropsychometry revealed impaired visual memory and naming in
      JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and
      controls exhibited a small world topology in their white matter networks, with no
      significant differences in the global multivariate network properties between the
      groups. The network-based statistic approach identified one subnetwork of
      hyperconnectivity in the JME group, involving primary motor, parietal and
      subcortical regions. Finally, there was a significant positive correlation in
      structural connectivity with cognitive task performance. CONCLUSIONS: Our
      findings suggest that structural changes in JME patients are distributed at a
      network level, beyond the frontal lobes. The identified subnetwork includes key
      structures in spike wave generation, along with primary motor areas, which may
      contribute to myoclonic jerks. We conclude that analyzing the affected
      subnetworks may provide new insights into understanding seizure generation, as
      well as the cognitive deficits observed in JME patients.

PMID- 25610772
TI  - Basal forebrain atrophy correlates with amyloid beta burden in Alzheimer's
      disease.
AB  - The brains of patients suffering from Alzheimer's disease (AD) have three
      classical pathological hallmarks: amyloid-beta (Abeta) plaques, tau tangles, and
      neurodegeneration, including that of cholinergic neurons of the basal forebrain.
      However the relationship between Abeta burden and basal forebrain degeneration
      has not been extensively studied. To investigate this association, basal
      forebrain volumes were determined from magnetic resonance images of controls,
      subjects with amnestic mild cognitive impairment (aMCI) and AD patients enrolled
      in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) and
      Australian Imaging, Biomarkers and Lifestyle (AIBL) studies. In the AIBL cohort,
      these volumes were correlated within groups to neocortical gray matter retention
      of Pittsburgh compound B (PiB) from positron emission tomography images as a
      measure of Abeta load. The basal forebrain volumes of AD and aMCI subjects were
      significantly reduced compared to those of control subjects. Anterior basal
      forebrain volume was significantly correlated to neocortical PiB retention in AD
      subjects and aMCI subjects with high Abeta burden, whereas posterior basal
      forebrain volume was significantly correlated to neocortical PiB retention in
      control subjects with high Abeta burden. Therefore this study provides new
      evidence for a correlation between neocortical Abeta accumulation and basal
      forebrain degeneration. In addition, cluster analysis showed that subjects with a
      whole basal forebrain volume below a determined cut-off value had a 7 times
      higher risk of having a worse diagnosis within ~18 months. 

PMID- 25610773
TI  - Fusion analysis of first episode depression: where brain shape deformations meet
      local composition of tissue.
AB  - Computational neuroanatomical techniques that are used to evaluate the structural
      correlates of disorders in the brain typically measure regional differences in
      gray matter or white matter, or measure regional differences in the deformation
      fields required to warp individual datasets to a standard space. Our aim in this
      study was to combine measurements of regional tissue composition and of
      deformations in order to characterize a particular brain disorder (here, major
      depressive disorder). We use structural Magnetic Resonance Imaging (MRI) data
      from young adults in a first episode of depression, and from an age- and sex
      matched group of non-depressed individuals, and create population gray matter
      (GM) and white matter (WM) tissue average templates using DARTEL groupwise
      registration. We obtained GM and WM tissue maps in the template space, along with
      the deformation fields required to co-register the DARTEL template and the GM and
      WM maps in the population. These three features, reflecting tissue composition
      and shape of the brain, were used within a joint independent-components analysis
      (jICA) to extract spatially independent joint sources and their corresponding
      modulation profiles. Coefficients of the modulation profiles were used to capture
      differences between depressed and non-depressed groups. The combination of
      hippocampal shape deformations and local composition of tissue (but neither shape
      nor local composition of tissue alone) was shown to discriminate reliably between
      individuals in a first episode of depression and healthy controls, suggesting
      that brain structural differences between depressed and non-depressed individuals
      do not simply reflect chronicity of the disorder but are there from the very
      outset. 

PMID- 25610774
TI  - Advanced [(18)F]FDG and [(11)C]flumazenil PET analysis for individual outcome
      prediction after temporal lobe epilepsy surgery for hippocampal sclerosis.
AB  - PURPOSE: We have previously shown that an imaging marker, increased
      periventricular [(11)C]flumazenil ([(11)C]FMZ) binding, is associated with
      failure to become seizure free (SF) after surgery for temporal lobe epilepsy
      (TLE) with hippocampal sclerosis (HS). Here, we investigated whether increased
      preoperative periventricular white matter (WM) signal can be detected on clinical
      [(18)F]FDG-PET images. We then explored the potential of periventricular FDG WM
      increases, as well as whole-brain [(11)C]FMZ and [(18)F]FDG images analysed with
      random forest classifiers, for predicting surgery outcome. METHODS: Sixteen
      patients with MRI-defined HS had preoperative [(18)F]FDG and [(11)C]FMZ-PET.
      Fifty controls had [(18)F]FDG-PET (30), [(11)C]FMZ-PET (41), or both (21).
      Periventricular WM signal was analysed using Statistical Parametric Mapping
      (SPM8), and whole-brain image classification was performed using random forests
      implemented in R (http://www.r-project.org). Surgery outcome was predicted at the
      group and individual levels. RESULTS: At the group level, non-seizure free (NSF)
      versus SF patients had periventricular increases with both tracers. Against
      controls, NSF patients showed more prominent periventricular [(11)C]FMZ and
      [(18)F]FDG signal increases than SF patients. All differences were more marked
      for [(11)C]FMZ. For individuals, periventricular WM signal increases were seen at
      optimized thresholds in 5/8 NSF patients for both tracers. For SF patients, 1/8
      showed periventricular signal increases for [(11)C]FMZ, and 4/8 for [(18)F]FDG.
      Hence, [(18)F]FDG had relatively poor sensitivity and specificity. Random forest
      classification accurately identified 7/8 SF and 7/8 NSF patients using [(11)C]FMZ
      images, but only 4/8 SF and 6/8 NSF patients with [(18)F]FDG. CONCLUSION: This
      study extends the association between periventricular WM increases and NSF
      outcome to clinical [(18)F]FDG-PET, but only at the group level. Whole-brain
      random forest classification increases [(11)C]FMZ-PET's performance for
      predicting surgery outcome.

PMID- 25610776
TI  - Mathematical models for the diffusion magnetic resonance signal abnormality in
      patients with prion diseases.
AB  - In clinical practice signal hyperintensity in the cortex and/or in the striatum
      on magnetic resonance (MR) diffusion-weighted images (DWIs) is a marker of
      sporadic Creutzfeldt-Jakob Disease (sCJD). MR diagnostic accuracy is greater than
      90%, but the biophysical mechanisms underpinning the signal abnormality are
      unknown. The aim of this prospective study is to combine an advanced DWI protocol
      with new mathematical models of the microstructural changes occurring in prion
      disease patients to investigate the cause of MR signal alterations. This
      underpins the later development of more sensitive and specific image-based
      biomarkers. DWI data with a wide a range of echo times and diffusion weightings
      were acquired in 15 patients with suspected diagnosis of prion disease and in 4
      healthy age-matched subjects. Clinical diagnosis of sCJD was made in nine
      patients, genetic CJD in one, rapidly progressive encephalopathy in three, and
      Gerstmann-Straussler-Scheinker syndrome in two. Data were analysed with two bi
      compartment models that represent different hypotheses about the
      histopathological alterations responsible for the DWI signal hyperintensity. A
      ROI-based analysis was performed in 13 grey matter areas located in affected and
      apparently unaffected regions from patients and healthy subjects. We provide for
      the first time non-invasive estimate of the restricted compartment radius,
      designed to reflect vacuole size, which is a key discriminator of sCJD subtypes.
      The estimated vacuole size in DWI hyperintense cortex was in the range between 3
      and 10 um that is compatible with neuropathology measurements. In DWI
      hyperintense grey matter of sCJD patients the two bi-compartment models
      outperform the classic mono-exponential ADC model. Both new models show that T2
      relaxation times significantly increase, fast and slow diffusivities reduce, and
      the fraction of the compartment with slow/restricted diffusion increases compared
      to unaffected grey matter of patients and healthy subjects. Analysis of the raw
      DWI signal allows us to suggest the following acquisition parameters for
      optimized detection of CJD lesions: b = 3000 s/mm(2) and TE = 103 ms. In
      conclusion, these results provide the first in vivo estimate of mean vacuole
      size, new insight on the mechanisms of DWI signal changes in prionopathies and
      open the way to designing an optimized acquisition protocol to improve early
      clinical diagnosis and subtyping of sCJD. 

PMID- 25610775
TI  - Capturing the dynamics of response variability in the brain in ADHD.
AB  - ADHD is characterized by increased intra-individual variability in response times
      during the performance of cognitive tasks. However, little is known about
      developmental changes in intra-individual variability, and how these changes
      relate to cognitive performance. Twenty subjects with ADHD aged 7-24 years and 20
      age-matched, typically developing controls participated in an fMRI-scan while
      they performed a go-no-go task. We fit an ex-Gaussian distribution on the
      response distribution to objectively separate extremely slow responses, related
      to lapses of attention, from variability on fast responses. We assessed
      developmental changes in these intra-individual variability measures, and
      investigated their relation to no-go performance. Results show that the ex
      Gaussian measures were better predictors of no-go performance than traditional
      measures of reaction time. Furthermore, we found between-group differences in the
      change in ex-Gaussian parameters with age, and their relation to task
      performance: subjects with ADHD showed age-related decreases in their variability
      on fast responses (sigma), but not in lapses of attention (tau), whereas control
      subjects showed a decrease in both measures of variability. For control subjects,
      but not subjects with ADHD, this age-related reduction in variability was
      predictive of task performance. This group difference was reflected in neural
      activation: for typically developing subjects, the age-related decrease in intra
      individual variability on fast responses (sigma) predicted activity in the dorsal
      anterior cingulate gyrus (dACG), whereas for subjects with ADHD, activity in this
      region was related to improved no-go performance with age, but not to intra
      individual variability. These data show that using more sophisticated measures of
      intra-individual variability allows the capturing of the dynamics of task
      performance and associated neural changes not permitted by more traditional
      measures. 

PMID- 25610777
TI  - Linked alterations in gray and white matter morphology in adults with high
      functioning autism spectrum disorder: a multimodal brain imaging study.
AB  - Growing evidence suggests that a broad range of behavioral anomalies in people
      with autism spectrum disorder (ASD) can be linked with morphological and
      functional alterations in the brain. However, the neuroanatomical underpinnings
      of ASD have been investigated using either structural magnetic resonance imaging
      (MRI) or diffusion tensor imaging (DTI), and the relationships between
      abnormalities revealed by these two modalities remain unclear. This study applied
      a multimodal data-fusion method, known as linked independent component analysis
      (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with
      ASD and 46 matched controls in order to elucidate associations between different
      aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite
      components that showed significant between-group differences, one of which was
      significantly correlated with age. In the other component, participants with ASD
      showed decreased gray matter (GM) volumes in multiple regions, including the
      bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and
      post-central gyri. These GM changes were linked with a pattern of decreased
      fractional anisotropy (FA) in several white matter tracts, such as the bilateral
      inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi,
      and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data
      revealed significant reductions of FA along with increased mean diffusivity in
      those tracts for ASD, providing further evidence of disrupted anatomical
      connectivity. Taken together, our findings suggest that, in ASD, alterations in
      different aspects of brain morphology may co-occur in specific brain networks,
      providing a comprehensive view for understanding the neuroanatomy of this
      disorder. 

PMID- 25610778
TI  - Performances of diffusion kurtosis imaging and diffusion tensor imaging in
      detecting white matter abnormality in schizophrenia.
AB  - Diffusion kurtosis imaging (DKI) is an extension of diffusion tensor imaging
      (DTI), exhibiting improved sensitivity and specificity in detecting developmental
      and pathological changes in neural tissues. However, little attention was paid to
      the performances of DKI and DTI in detecting white matter abnormality in
      schizophrenia. In this study, DKI and DTI were performed in 94 schizophrenia
      patients and 91 sex- and age-matched healthy controls. White matter integrity was
      assessed by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity
      (AD), radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK) and radial
      kurtosis (RK) of DKI and FA, MD, AD and RD of DTI. Group differences in these
      parameters were compared using tract-based spatial statistics (TBSS) (P < 0.01,
      corrected). The sensitivities in detecting white matter abnormality in
      schizophrenia were MK (34%) > AK (20%) > RK (3%) and RD (37%) > FA (24%) > MD
      (21%) for DKI, and RD (43%) > FA (30%) > MD (21%) for DTI. DKI-derived diffusion
      parameters (RD, FA and MD) were sensitive to detect abnormality in white matter
      regions (the corpus callosum and anterior limb of internal capsule) with coherent
      fiber arrangement; however, the kurtosis parameters (MK and AK) were sensitive to
      reveal abnormality in white matter regions (the juxtacortical white matter and
      corona radiata) with complex fiber arrangement. In schizophrenia, the decreased
      AK suggests axonal damage; however, the increased RD indicates myelin impairment.
      These findings suggest that diffusion and kurtosis parameters could provide
      complementary information and they should be jointly used to reveal pathological
      changes in schizophrenia. 

PMID- 25610779
TI  - Cortical thickness abnormalities associated with dyslexia, independent of
      remediation status.
AB  - Abnormalities in cortical structure are commonly observed in children with
      dyslexia in key regions of the "reading network." Whether alteration in cortical
      features reflects pathology inherent to dyslexia or environmental influence
      (e.g., impoverished reading experience) remains unclear. To address this
      question, we compared MRI-derived metrics of cortical thickness (CT), surface
      area (SA), gray matter volume (GMV), and their lateralization across three
      different groups of children with a historical diagnosis of dyslexia, who varied
      in current reading level. We compared three dyslexia subgroups with: (1)
      persistent reading and spelling impairment; (2) remediated reading impairment
      (normal reading scores), and (3) remediated reading and spelling impairments
      (normal reading and spelling scores); and a control group of (4) typically
      developing children. All groups were matched for age, gender, handedness, and IQ.
      We hypothesized that the dyslexia group would show cortical abnormalities in
      regions of the reading network relative to controls, irrespective of remediation
      status. Such a finding would support that cortical abnormalities are inherent to
      dyslexia and are not a consequence of abnormal reading experience. Results
      revealed increased CT of the left fusiform gyrus in the dyslexia group relative
      to controls. Similarly, the dyslexia group showed CT increase of the right
      superior temporal gyrus, extending into the planum temporale, which resulted in a
      rightward CT asymmetry on lateralization indices. There were no group differences
      in SA, GMV, or their lateralization. These findings held true regardless of
      remediation status. Each reading level group showed the same "double hit" of
      atypically increased left fusiform CT and rightward superior temporal CT
      asymmetry. Thus, findings provide evidence that a developmental history of
      dyslexia is associated with CT abnormalities, independent of remediation status. 

PMID- 25610780
TI  - Brain metabolic maps in Mild Cognitive Impairment predict heterogeneity of
      progression to dementia.
AB  - [(18)F]FDG-PET imaging has been recognized as a crucial diagnostic marker in Mild
      Cognitive Impairment (MCI), supporting the presence or the exclusion of
      Alzheimer's Disease (AD) pathology. A clinical heterogeneity, however, underlies
      MCI definition. In this study, we aimed to evaluate the predictive role of single
      subject voxel-based maps of [(18)F]FDG distribution generated through statistical
      parametric mapping (SPM) in the progression to different dementia subtypes in a
      sample of 45 MCI. Their scans were compared to a large normal reference dataset
      developed and validated for comparison at single-subject level. Additionally,
      Abeta42 and Tau CSF values were available in 34 MCI subjects. Clinical follow-up
      (mean 28.5 +/- 7.8 months) assessed subsequent progression to AD or non-AD
      dementias. The SPM analysis showed: 1) normal brain metabolism in 14 MCI cases,
      none of them progressing to dementia; 2) the typical temporo-parietal pattern
      suggestive for prodromal AD in 15 cases, 11 of them progressing to AD; 3) brain
      hypometabolism suggestive of frontotemporal lobar degeneration (FTLD) subtypes in
      7 and dementia with Lewy bodies (DLB) in 2 subjects (all fulfilled FTLD or DLB
      clinical criteria at follow-up); and 4) 7 MCI cases showed a selective unilateral
      or bilateral temporo-medial hypometabolism without the typical AD pattern, and
      they all remained stable. In our sample, objective voxel-based analysis of
      [(18)F]FDG-PET scans showed high predictive prognostic value, by identifying
      either normal brain metabolism or hypometabolic patterns suggestive of different
      underlying pathologies, as confirmed by progression at follow-up. These data
      support the potential usefulness of this SPM [(18)F]FDG PET analysis in the early
      dementia diagnosis and for improving subject selection in clinical trials based
      on MCI definition. 

PMID- 25610781
TI  - Reduced hippocampal volume and hypothalamus-pituitary-adrenal axis function in
      first episode psychosis: evidence for sex differences.
AB  - BACKGROUND: Hippocampal volume (HV) decline is an important marker of psychosis
      and has been associated with hypothalamus-pituitary-adrenal (HPA) axis
      dysregulation in various disorders. Given recent findings of sex differences in
      HPA axis function in psychosis, the current study investigated differences in HV
      in male and female first episode psychosis (FEP) patients and controls and the
      interaction of HV with the cortisol awakening response (CAR) and symptoms.
      METHODS: Fifty-eight patients with a diagnosis of FEP (39 men, 19 women) and 27
      healthy community controls (15 men, 12 women) underwent structural magnetic
      resonance imaging (MRI) on a 1.5 T scanner. Hippocampal volume was determined
      using previously established segmentation protocols. Saliva samples for cortisol
      assessment were collected at 0, 30 and 60 min after awakening. Psychotic symptoms
      were assessed with the Scale for Assessment of Positive Symptoms (SAPS), the
      Scale for Assessment of Negative Symptoms (SANS) and the Global Assessment of
      Functioning (GAF) scale. RESULTS: Male patients had significantly smaller left
      and right HVs compared to male controls, which appeared to be secondary to global
      brain volume differences. However, even when controlling for overall brain size,
      male patients showed smaller HV compared to female patients. The CAR was
      significantly lower in male patients compared to male controls and female
      patients. Only in male patients, smaller left HV was significantly associated
      with a blunted CAR, and smaller HV bilaterally was related to positive psychotic
      symptoms and lower levels of functioning. CONCLUSIONS: We propose that reduced
      hippocampal volume and an attenuated cortisol awakening response are related
      markers of increased stress vulnerability in male psychosis patients and that
      both contribute to the unfavorable clinical picture in men.

PMID- 25610782
TI  - Early neural activation during facial affect processing in adolescents with
      Autism Spectrum Disorder.
AB  - Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder
      (ASD). Emotional faces are arguably the most critical visual social stimuli and
      the ability to perceive, recognize, and interpret emotions is central to social
      interaction and communication, and subsequently healthy social development.
      However, our understanding of the neural and cognitive mechanisms underlying
      emotional face processing in adolescents with ASD is limited. We recruited 48
      adolescents, 24 with high functioning ASD and 24 typically developing controls.
      Participants completed an implicit emotional face processing task in the MEG. We
      examined spatiotemporal differences in neural activation between the groups
      during implicit angry and happy face processing. While there were no differences
      in response latencies between groups across emotions, adolescents with ASD had
      lower accuracy on the implicit emotional face processing task when the trials
      included angry faces. MEG data showed atypical neural activity in adolescents
      with ASD during angry and happy face processing, which included atypical activity
      in the insula, anterior and posterior cingulate and temporal and orbitofrontal
      regions. Our findings demonstrate differences in neural activity during happy and
      angry face processing between adolescents with and without ASD. These differences
      in activation in social cognitive regions may index the difficulties in face
      processing and in comprehension of social reward and punishment in the ASD group.
      Thus, our results suggest that atypical neural activation contributes to impaired
      affect processing, and thus social cognition, in adolescents with ASD. 

PMID- 25610783
TI  - Evoked itch perception is associated with changes in functional brain
      connectivity.
AB  - Chronic itch, a highly debilitating condition, has received relatively little
      attention in the neuroimaging literature. Recent studies suggest that brain
      regions supporting itch in chronic itch patients encompass sensorimotor and
      salience networks, and corticostriatal circuits involved in motor preparation for
      scratching. However, how these different brain areas interact with one another in
      the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic
      dermatitis patients to investigate resting-state functional connectivity before
      and after allergen-induced itch exacerbated the clinical itch perception in these
      patients. A seed-based analysis revealed decreased functional connectivity from
      baseline resting state to the evoked-itch state between several itch-related
      brain regions, particularly the insular and cingulate cortices and basal ganglia,
      where decreased connectivity was significantly correlated with increased levels
      of perceived itch. In contrast, evoked itch increased connectivity between key
      nodes of the frontoparietal control network (superior parietal lobule and
      dorsolateral prefrontal cortex), where higher increase in connectivity was
      correlated with a lesser increase in perceived itch, suggesting that greater
      interaction between nodes of this executive attention network serves to limit
      itch sensation via enhanced top-down regulation. Overall, our results provide the
      first evidence of itch-dependent changes in functional connectivity across
      multiple brain regions. 

PMID- 25610784
TI  - Distinct frontal lobe morphology in girls and boys with ADHD.
AB  - OBJECTIVE: This study investigated whether frontal lobe cortical morphology
      differs for boys and girls with ADHD (ages 8-12 years) in comparison to typically
      developing (TD) peers. METHOD: Participants included 226 children between the
      ages of 8-12 including 93 children with ADHD (29 girls) and 133 TD children (42
      girls) for which 3T MPRAGE MRI scans were obtained. A fully automated frontal
      lobe atlas was used to generate functionally distinct frontal subdivisions, with
      surface area (SA) and cortical thickness (CT) assessed in each region. Analyses
      focused on overall diagnostic differences as well as examinations of the effect
      of diagnosis within boys and girls. RESULTS: Girls, but not boys, with ADHD
      showed overall reductions in total prefrontal cortex (PFC) SA. Localization
      revealed that girls showed widely distributed reductions in the bilateral
      dorsolateral PFC, left inferior lateral PFC, right medial PFC, right
      orbitofrontal cortex, and left anterior cingulate; and boys showed reduced SA
      only in the right anterior cingulate and left medial PFC. In contrast, boys, but
      not girls, with ADHD showed overall reductions in total premotor cortex (PMC) SA.
      Further localization revealed that in boys, premotor reductions were observed in
      bilateral lateral PMC regions; and in girls reductions were observed in bilateral
      supplementary motor complex. In line with diagnostic group differences, PMC and
      PFC SAs were inversely correlated with symptom severity in both girls and boys
      with ADHD. CONCLUSIONS: These results elucidate sex-based differences in cortical
      morphology of functional subdivisions of the frontal lobe and provide additional
      evidence of associations among SA and symptom severity in children with ADHD.

PMID- 25610785
TI  - Presurgical language lateralization assessment by fMRI and dichotic listening of
      pediatric patients with intractable epilepsy.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical use of a method to
      assess hemispheric language dominance in pediatric candidates for epilepsy
      surgery. The method is designed for patients but has previously been evaluated
      with healthy children. METHODS: Nineteen patients, 8-18 years old, with
      intractable epilepsy and candidates for epilepsy surgery were assessed. The
      assessment consisted of two functional MRI protocols (fMRI) intended to target
      frontal and posterior language networks respectively, and a behavioral dichotic
      listening task (DL). Regional left/right indices for each fMRI task from the
      frontal, temporal and parietal lobe were calculated, and left/right indices of
      the DL task were calculated from responses of consonants and vowels, separately.
      A quantitative analysis of each patient's data set was done in two steps based on
      clearly specified criteria. First, fMRI data and DL data were analyzed separately
      to determine whether the result from each of these assessments were conclusive or
      not. Thereafter, the results from the individual assessments were combined to
      reach a final conclusion regarding hemispheric language dominance. RESULTS: For
      14 of the 19 subjects (74%) a conclusion was reached about their hemispheric
      language dominance. Nine subjects had a left-sided and five subjects had a right
      sided hemispheric dominance. In three cases (16%) DL provided critical data to
      reach a conclusive result. CONCLUSIONS: The success rate of conclusive language
      lateralization assessments in this study is comparable to reported rates on
      similar challenged pediatric populations. The results are promising but data from
      more patients than in the present study will be required to conclude on the
      clinical applicability of the method.

PMID- 25610786
TI  - Training-induced improvements in postural control are accompanied by alterations
      in cerebellar white matter in brain injured patients.
AB  - We investigated whether balance control in young TBI patients can be promoted by
      an 8-week balance training program and whether this is associated with
      neuroplastic alterations in brain structure. The cerebellum and cerebellar
      peduncles were selected as regions of interest because of their importance in
      postural control as well as their vulnerability to brain injury. Young patients
      with moderate to severe TBI and typically developing (TD) subjects participated
      in balance training using PC-based portable balancers with storage of training
      data and real-time visual feedback. An additional control group of TD subjects
      did not attend balance training. Mean diffusivity and fractional anisotropy were
      determined with diffusion MRI scans and were acquired before, during (4 weeks)
      and at completion of training (8 weeks) together with balance assessments on the
      EquiTest(r) System (NeuroCom) which included the Sensory Organization Test,
      Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI
      patients showed significant improvements on all EquiTest protocols, as well as a
      significant increase in mean diffusivity in the inferior cerebellar peduncle.
      Moreover, in both training groups, diffusion metrics in the cerebellum and/or
      cerebellar peduncles at baseline were predictive of the amount of performance
      increase after training. Finally, amount of training-induced improvement on the
      Rhythmic Weight Shift test in TBI patients was positively correlated with amount
      of change in fractional anisotropy in the inferior cerebellar peduncle. This
      suggests that training-induced plastic changes in balance control are associated
      with alterations in the cerebellar white matter microstructure in TBI patients. 

PMID- 25610787
TI  - Association of regional gray matter volumes in the brain with disruptive behavior
      disorders in male and female children.
AB  - Because the disruptive behavior disorders are highly impairing conditions, it is
      important to determine if structural variations in brain are associated early in
      life with these problems among children. Structural MRI data were acquired from
      111 9-11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for
      oppositional defiant disorder and/or conduct disorder and 68 healthy controls.
      Voxel-based morphometry was used to examine associations of behavioral measures
      with gray matter volumes in whole-brain analyses. Unlike previous studies,
      variation in gray matter volume was not found to be associated with a disruptive
      behavior disorder diagnosis in any brain region at p < .05 with FWE correction.
      Nonetheless, an inverse nonlinear association of the number of conduct disorder
      (CD) symptoms with gray matter volume along the left superior temporal sulcus was
      significant in the full sample (p < .05 with FWE correction), with a trend in the
      right hemisphere (p < 0.001 uncorrected). There also was a trend toward a
      stronger association of the number of CD symptoms with gray matter volume along
      the left superior temporal sulcus in girls than boys. The present findings did
      not replicate previous findings of reduced gray matter volumes in the anterior
      insula, amygdala, and frontal cortex in youth with CD, but are consistent with
      previous findings of reduced gray matter volumes in temporal regions,
      particularly in girls. 

PMID- 25610788
TI  - Sugihara causality analysis of scalp EEG for detection of early Alzheimer's
      disease.
AB  - Recently, Sugihara proposed an innovative causality concept, which, in contrast
      to statistical predictability in Granger sense, characterizes underlying
      deterministic causation of the system. This work exploits Sugihara causality
      analysis to develop novel EEG biomarkers for discriminating normal aging from
      mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The
      hypothesis of this work is that scalp EEG based causality measurements have
      different distributions for different cognitive groups and hence the causality
      measurements can be used to distinguish between NC, MCI, and AD participants. The
      current results are based on 30-channel resting EEG records from 48 age-matched
      participants (mean age 75.7 years) - 15 normal controls (NCs), 16 MCI, and 17
      early-stage AD. First, a reconstruction model is developed for each EEG channel,
      which predicts the signal in the current channel using data of the other 29
      channels. The reconstruction model of the target channel is trained using NC,
      MCI, or AD records to generate an NC-, MCI-, or AD-specific model, respectively.
      To avoid over fitting, the training is based on the leave-one-out principle.
      Sugihara causality between the channels is described by a quality score based on
      comparison between the reconstructed signal and the original signal. The quality
      scores are studied for their potential as biomarkers to distinguish between the
      different cognitive groups. First, the dimension of the quality scores is reduced
      to two principal components. Then, a three-way classification based on the
      principal components is conducted. Accuracies of 95.8%, 95.8%, and 97.9% are
      achieved for resting eyes open, counting eyes closed, and resting eyes closed
      protocols, respectively. This work presents a novel application of Sugihara
      causality analysis to capture characteristic changes in EEG activity due to
      cognitive deficits. The developed method has excellent potential as
      individualized biomarkers in the detection of pathophysiological changes in early
      stage AD. 

PMID- 25610789
TI  - Specific functional connectivity alterations of the dorsal striatum in young
      people with depression.
AB  - BACKGROUND: Altered basal ganglia function has been implicated in the
      pathophysiology of youth Major Depressive Disorder (MDD). Studies have generally
      focused on characterizing abnormalities in ventral "affective" corticostriatal
      loops supporting emotional processes. Recent evidence however, has implicated
      alterations in functional connectivity of dorsal "cognitive" corticostriatal
      loops in youth MDD. The contribution of dorsal versus ventral corticostriatal
      alterations to the pathophysiology of youth MDD remains unclear. METHODS: Twenty
      one medication-free patients with moderate-to-severe MDD between the ages of 15
      and 24 years old were matched with 21 healthy control participants. Using resting
      state functional connectivity magnetic resonance imaging we systematically
      investigated connectivity of eight dorsal and ventral subdivisions of the
      striatum. Voxelwise statistical maps of each subregion's connectivity with other
      brain areas were compared between the depressed and control groups. RESULTS:
      Depressed youths showed alterations in functional connectivity that were confined
      to the dorsal corticostriatal circuit. Compared to controls, depressed patients
      showed increased connectivity between the dorsal caudate nucleus and
      ventrolateral prefrontal cortex bilaterally. Increased depression severity
      correlated with the magnitude of dorsal caudate connectivity with the right
      dorsolateral prefrontal cortex. There were no significant between-group
      differences in connectivity of ventral striatal regions. CONCLUSIONS: The results
      provide evidence that alterations in corticostriatal connectivity are evident at
      the early stages of the illness and are not a result of antidepressant treatment.
      Increased connectivity between the dorsal caudate, which is usually associated
      with cognitive processes, and the more affectively related ventrolateral
      prefrontal cortex may reflect a compensatory mechanism for dysfunctional
      cognitive-emotional processing in youth depression.

PMID- 25610790
TI  - Thalamic functional connectivity predicts seizure laterality in individual TLE
      patients: application of a biomarker development strategy.
AB  - Noninvasive markers of brain function could yield biomarkers in many neurological
      disorders. Disease models constrained by coordinate-based meta-analysis are
      likely to increase this yield. Here, we evaluate a thalamic model of temporal
      lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended
      in a diffusion tractography study of an independent patient population.
      Specifically, we evaluated whether thalamic functional connectivity (resting
      state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality,
      as established with intracranial EEG. Twenty-four lesional and non-lesional
      temporal lobe epilepsy patients were studied. No significant differences in
      functional connection strength in patient and control groups were observed with
      Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack
      of group differences, individual patient difference scores (from control mean
      connection strength) successfully predicted seizure onset zone as shown in ROC
      curves: discriminant analysis (two-dimensional) predicted seizure onset zone with
      85% sensitivity and 91% specificity; logistic regression (four-dimensional)
      achieved 86% sensitivity and 100% specificity. The strongest markers in both
      analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex
      functional connection strength. Thus, this study shows that thalamic functional
      connections are sensitive and specific markers of seizure onset laterality in
      individual temporal lobe epilepsy patients. This study also advances an overall
      strategy for the programmatic development of neuroimaging biomarkers in clinical
      and genetic populations: a disease model informed by coordinate-based meta
      analysis was used to anatomically constrain individual patient analyses. 

PMID- 25610791
TI  - Predicting outcome in clinically isolated syndrome using machine learning.
AB  - We aim to determine if machine learning techniques, such as support vector
      machines (SVMs), can predict the occurrence of a second clinical attack, which
      leads to the diagnosis of clinically-definite Multiple Sclerosis (CDMS) in
      patients with a clinically isolated syndrome (CIS), on the basis of single
      patient's lesion features and clinical/demographic characteristics. Seventy-four
      patients at onset of CIS were scanned and clinically reviewed after one and three
      years. CDMS was used as the gold standard against which SVM classification
      accuracy was tested. Radiological features related to lesional characteristics on
      conventional MRI were defined a priori and used in combination with
      clinical/demographic features in an SVM. Forward recursive feature elimination
      with 100 bootstraps and a leave-one-out cross-validation was used to find the
      most predictive feature combinations. 30 % and 44 % of patients developed CDMS
      within one and three years, respectively. The SVMs correctly predicted the
      presence (or the absence) of CDMS in 71.4 % of patients (sensitivity/specificity:
      77 %/66 %) at 1 year, and in 68 % (60 %/76 %) at 3 years on average over all
      bootstraps. Combinations of features consistently gave a higher accuracy in
      predicting outcome than any single feature. Machine-learning-based
      classifications can be used to provide an "individualised" prediction of
      conversion to MS from subjects' baseline scans and clinical characteristics, with
      potential to be incorporated into routine clinical practice. 

PMID- 25610792
TI  - Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.
AB  - Increased functional connectivity in resting state networks was found in several
      studies of patients with motor neuron disorders, although diffusion tensor
      imaging studies consistently show loss of white matter integrity. To understand
      the relationship between structural connectivity and functional connectivity, we
      examined the structural connections between regions with altered functional
      connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor
      neuron disease. Connectivity matrices were constructed from resting state fMRI in
      16 PLS patients to identify areas of differing connectivity between patients and
      healthy controls. Probabilistic fiber tracking was used to examine structural
      connections between regions of differing connectivity. PLS patients had 12
      regions with increased functional connectivity compared to controls, with a
      predominance of cerebro-cerebellar connections. Increased functional connectivity
      was strongest between the cerebellum and cortical motor areas and between the
      cerebellum and frontal and temporal cortex. Fiber tracking detected no difference
      in connections between regions with increased functional connectivity. We
      conclude that functional connectivity changes are not strongly based in
      structural connectivity. Increased functional connectivity may be caused by
      common inputs, or by reduced selectivity of cortical activation, which could
      result from loss of intracortical inhibition when cortical afferents are intact. 

PMID- 25610793
TI  - Increased cortical surface area and gyrification following long-term survival
      from early monocular enucleation.
AB  - PURPOSE: Retinoblastoma is typically diagnosed before 5 years of age and is often
      treated by enucleation (surgical removal) of the cancerous eye. Here, we sought
      to characterize morphological changes of the cortex following long-term survival
      from early monocular enucleation. METHODS: Nine adults with early right-eye
      enucleation (<=48 months of age) due to retinoblastoma were compared to 18
      binocularly intact controls. Surface area, cortical thickness, and gyrification
      estimates were obtained from T1 weighted images and group differences were
      examined. RESULTS: Early monocular enucleation was associated with increased
      surface area and/or gyrification in visual (i.e., V1, inferior temporal),
      auditory (i.e., supramarginal), and multisensory (i.e., superior temporal,
      inferior parietal, superior parietal) cortices compared with controls. Visual
      cortex increases were restricted to the right hemisphere contralateral to the
      remaining eye, consistent with previous subcortical data showing asymmetrical
      lateral geniculate nucleus volume following early monocular enucleation.
      CONCLUSIONS: Altered morphological development of visual, auditory, and
      multisensory regions occurs subsequent to long-time survival from early eye loss.

PMID- 25610794
TI  - Source retrieval is not properly differentiated from object retrieval in early
      schizophrenia: an fMRI study using virtual reality.
AB  - Source memory, the ability to identify the context in which a memory occurred, is
      impaired in schizophrenia and has been related to clinical symptoms such as
      hallucinations. The neurobiological underpinnings of this deficit are not well
      understood. Twenty-five patients with recent onset schizophrenia (within the
      first 4.5 years of treatment) and twenty-four healthy controls completed a source
      memory task. Participants navigated through a 3D virtual city, and had 20
      encounters of an object with a person at a place. Functional magnetic resonance
      imaging was performed during a subsequent forced-choice recognition test. Two
      objects were presented and participants were asked to either identify which
      object was seen (new vs. old object recognition), or identify which of the two
      old objects was associated with either the person or the place being presented
      (source memory recognition). Source memory was examined by contrasting person or
      place with object. Both patients and controls demonstrated significant neural
      activity to source memory relative to object memory, though activity in controls
      was much more widespread. Group differences were observed in several regions,
      including the medial parietal and cingulate cortex, lateral frontal lobes and
      right superior temporal gyrus. Patients with schizophrenia did not differentiate
      between source and object memory in these regions. Positive correlations with
      hallucination proneness were observed in the left frontal and right middle
      temporal cortices and cerebellum. Patients with schizophrenia have a deficit in
      the neural circuits which facilitate source memory, which may underlie both the
      deficits in this domain and be related to auditory hallucinations. 

PMID- 25610795
TI  - Classification algorithms with multi-modal data fusion could accurately
      distinguish neuromyelitis optica from multiple sclerosis.
AB  - Neuromyelitis optica (NMO) exhibits substantial similarities to multiple
      sclerosis (MS) in clinical manifestations and imaging results and has long been
      considered a variant of MS. With the advent of a specific biomarker in NMO, known
      as anti-aquaporin 4, this assumption has changed; however, the differential
      diagnosis remains challenging and it is still not clear whether a combination of
      neuroimaging and clinical data could be used to aid clinical decision-making.
      Computer-aided diagnosis is a rapidly evolving process that holds great promise
      to facilitate objective differential diagnoses of disorders that show similar
      presentations. In this study, we aimed to use a powerful method for multi-modal
      data fusion, known as a multi-kernel learning and performed automatic diagnosis
      of subjects. We included 30 patients with NMO, 25 patients with MS and 35 healthy
      volunteers and performed multi-modal imaging with T1-weighted high resolution
      scans, diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). In
      addition, subjects underwent clinical examinations and cognitive assessments. We
      included 18 a priori predictors from neuroimaging, clinical and cognitive
      measures in the initial model. We used 10-fold cross-validation to learn the
      importance of each modality, train and finally test the model performance. The
      mean accuracy in differentiating between MS and NMO was 88%, where visible white
      matter lesion load, normal appearing white matter (DTI) and functional
      connectivity had the most important contributions to the final classification. In
      a multi-class classification problem we distinguished between all of 3 groups
      (MS, NMO and healthy controls) with an average accuracy of 84%. In this
      classification, visible white matter lesion load, functional connectivity, and
      cognitive scores were the 3 most important modalities. Our work provides
      preliminary evidence that computational tools can be used to help make an
      objective differential diagnosis of NMO and MS. 

PMID- 25610796
TI  - Brain structural connectivity increases concurrent with functional improvement:
      evidence from diffusion tensor MRI in children with cerebral palsy during
      therapy.
AB  - Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non
      progressive movement disorders caused by injury to the developing fetal or infant
      brain (Bax et al., 2005). Because of its serious long-term consequences,
      effective interventions that can help improve motor function, independence, and
      quality of life are critically needed. Our ongoing longitudinal clinical trial to
      treat children with CP is specifically designed to meet this challenge. To
      maximize the potential for functional improvement, all children in this trial
      received autologous cord blood transfusions (with order randomized with a placebo
      administration over 2 years) in conjunction with more standard physical and
      occupational therapies. As a part of this trial, magnetic resonance imaging (MRI)
      is used to improve our understanding of how these interventions affect brain
      development, and to develop biomarkers of treatment efficacy. In this report,
      diffusion tensor imaging (DTI) and subsequent brain connectome analyses were
      performed in a subset of children enrolled in the clinical trial (n = 17), who
      all exhibited positive but varying degrees of functional improvement over the
      first 2-year period of the study. Strong correlations between increases in white
      matter (WM) connectivity and functional improvement were demonstrated; however no
      significant relationships between either of these factors with the age of the
      child at time of enrollment were identified. Thus, our data indicate that
      increases in brain connectivity reflect improved functional abilities in children
      with CP. In future work, this potential biomarker can be used to help
      differentiate the underlying mechanisms of functional improvement, as well as to
      identify treatments that can best facilitate functional improvement upon un
      blinding of the timing of autologous cord blood transfusions at the completion of
      this study. 

PMID- 25610797
TI  - Altered neural connectivity during response inhibition in adolescents with
      attention-deficit/hyperactivity disorder and their unaffected siblings.
AB  - INTRODUCTION: Response inhibition is one of the executive functions impaired in
      attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates
      that altered functional and structural neural connectivity are part of the
      neurobiological basis of ADHD. Here, we investigated if adolescents with ADHD
      show altered functional connectivity during response inhibition compared to their
      unaffected siblings and healthy controls. METHODS: Response inhibition was
      assessed using the stop signal paradigm. Functional connectivity was assessed
      using psycho-physiological interaction analyses applied to BOLD time courses from
      seed regions within inferior- and superior frontal nodes of the response
      inhibition network. Resulting networks were compared between adolescents with
      ADHD (N = 185), their unaffected siblings (N = 111), and controls (N = 125).
      RESULTS: Control subjects showed stronger functional connectivity than the other
      two groups within the response inhibition network, while subjects with ADHD
      showed relatively stronger connectivity between default mode network (DMN) nodes.
      Stronger connectivity within the response inhibition network was correlated with
      lower ADHD severity, while stronger connectivity with the DMN was correlated with
      increased ADHD severity. Siblings showed connectivity patterns similar to
      controls during successful inhibition and to ADHD subjects during failed
      inhibition. Additionally, siblings showed decreased connectivity with the primary
      motor areas as compared to both participants with ADHD and controls. DISCUSSION:
      Subjects with ADHD fail to integrate activation within the response inhibition
      network and to inhibit connectivity with task-irrelevant regions. Unaffected
      siblings show similar alterations only during failed stop trials, as well as
      unique suppression of motor areas, suggesting compensatory strategies. These
      findings support the role of altered functional connectivity in understanding the
      neurobiology and familial transmission of ADHD.

PMID- 25610798
TI  - Altered cognition-related brain activity and interactions with acute pain in
      migraine.
AB  - Little is known about the effect of migraine on neural cognitive networks.
      However, cognitive dysfunction is increasingly being recognized as a comorbidity
      of chronic pain. Pain appears to affect cognitive ability and the function of
      cognitive networks over time, and decrements in cognitive function can exacerbate
      affective and sensory components of pain. We investigated differences in
      cognitive processing and pain-cognition interactions between 14 migraine patients
      and 14 matched healthy controls using an fMRI block-design with two levels of
      task difficulty and concurrent heat (painful and not painful) stimuli. Across
      groups, cognitive networks were recruited in response to a difficult cognitive
      task, and a pain-task interaction was found in the right (contralateral to pain
      stimulus) posterior insula (pINS), such that activity was modulated by decreasing
      the thermal pain stimulus or by engaging the difficult cognitive task. Migraine
      patients had less task-related deactivation within the left dorsolateral
      prefrontal cortex (DLPFC) and left dorsal anterior midcingulate cortex (aMCC)
      compared to controls. These regions have been reported to have decreased cortical
      thickness and cognitive-related deactivation within other pain populations, and
      are also associated with pain regulation, suggesting that the current findings
      may reflect altered cognitive function and top-down regulation of pain. During
      pain conditions, patients had decreased task-related activity, but more
      widespread task-related reductions in pain-related activity, compared to
      controls, suggesting cognitive resources may be diverted from task-related to
      pain-reduction-related processes in migraine. Overall, these findings suggest
      that migraine is associated with altered cognitive-related neural activity, which
      may reflect altered pain regulatory processes as well as broader functional
      restructuring. 

PMID- 25610799
TI  - Non-invasive evaluation of culprit lesions by PET imaging: shifting the clinical
      paradigm away from resultant anatomy toward causative physiology.
AB  - Although coronary angiography is the gold standard for assessing coronary artery
      disease (CAD), there is at best a weak correlation between degree of stenosis and
      the risk of developing cardiac events. Plaque rupture is the most common type of
      plaque complication, accounting for about 70% of fatal acute myocardial
      infarctions or sudden coronary deaths. Recently, the feasibility of (18)F
      fluoride PET/CT in the evaluation of atherosclerotic lesions was assessed.
      Radionuclide techniques allow non-invasive biologic assessment of atherosclerotic
      plaques. This may help to further shift the clinical paradigm in coronary disease
      away from anatomy toward causative physiology and biology. 

PMID- 25610800
TI  - Epicardial adipose tissue: far more than a fat depot.
AB  - Epicardial adipose tissue (EAT) refers to the fat depot that exists on the
      surface of the myocardium and is contained entirely beneath the pericardium, thus
      surrounding and in direct contact with the major coronary arteries and their
      branches. EAT is a biologically active organ that may play a role in the
      association between obesity and coronary artery disease (CAD). Given recent
      advances in non-invasive imaging modalities such a multidetector computed
      tomography (MDCT), EAT can be accurately measured and quantified. In this review,
      we focus on the evidence suggesting a role for EAT as a quantifiable risk marker
      in CAD, as well as describe the role EAT may play in the development and
      vulnerability of coronary artery plaque. 

PMID- 25610802
TI  - The subcutaneous ICD-current evidence and challenges.
AB  - The subcutaneous implantable cardioverter-defibrillator (S-ICD) represents an
      exciting development in ICD technology. It has relative advantages over
      traditional transvenous systems, particularly for young patients in whom the
      lifetime risk of device-related complications may be deemed to be unacceptably
      high. While data relating to device longevity and long term safety profile is yet
      to be accrued, several recent studies have demonstrated good clinical efficacy
      comparable to transvenous ICDs. Indeed, new techniques have also been developed
      to simplify the S-ICD implantation procedure and attempts have been made to
      address challenges pertaining to T-wave oversensing to reduce the delivery of
      inappropriate shocks. The impact of inappropriate shocks and lack of anti
      tachycardia pacing (ATP) function are not only contentious matters, but also have
      important implications for patients in whom the S-ICD would be suitable. It is
      envisaged that subsequent models of this device will be less cumbersome, with the
      possibility that an entirely leadless pacemaker-defibrillator will one day be
      possible. Although the S-ICD may not completely replace transvenous devices in
      its current form, evidence suggests that it is a viable alternative particularly
      in preventing sudden cardiac death in non-pacing dependent patients. 

PMID- 25610801
TI  - Cardiac CT: atherosclerosis to acute coronary syndrome.
AB  - Coronary computed tomographic angiography (CCTA) is a robust non-invasive method
      to assess coronary artery disease (CAD). Qualitative and quantitative assessment
      of atherosclerotic coronary stenosis with CCTA has been favourably compared with
      invasive coronary angiography (ICA) and intravascular ultrasound (IVUS).
      Importantly, it allows the study of preclinical stages of atherosclerotic
      disease, may help improve risk stratification and monitor the progressive course
      of the disease. The diagnostic accuracy of CCTA in the assessment of coronary
      artery bypass grafts (CABG) is excellent and the constantly improving technology
      is making the evaluation of stents feasible. Novel techniques are being developed
      to assess the functional significance of coronary stenosis. The excellent
      negative predictive value of CCTA in ruling out disease enables early and safe
      discharge of patients with suspected acute coronary syndromes (ACS) in the
      Emergency Department (ED). In addition, CCTA is useful in predicting clinical
      outcomes based on the extent of coronary atherosclerosis and also based on
      individual plaque characteristics such as low attenuation plaque (LAP), positive
      remodelling and spotty calcification. In this article, we review the role of CCTA
      in the detection of coronary atherosclerosis in native vessels, stented vessels,
      calcified arteries and grafts; the assessment of plaque progression, evaluation
      of chest pain in the ED, assessment of functional significance of stenosis and
      the prognostic significance of CCTA. 

PMID- 25610804
TI  - Coronary CTA using scout-based automated tube potential and current selection
      algorithm, with breast displacement results in lower radiation exposure in
      females compared to males.
AB  - PURPOSE: To evaluate the effect of automatic tube potential selection and
      automatic exposure control combined with female breast displacement during
      coronary computed tomography angiography (CCTA) on radiation exposure in women
      versus men of the same body size. MATERIALS AND METHODS: Consecutive clinical
      exams between January 2012 and July 2013 at an academic medical center were
      retrospectively analyzed. All examinations were performed using ECG-gating,
      automated tube potential, and tube current selection algorithm (APS-AEC) with
      breast displacement in females. Cohorts were stratified by sex and standard World
      Health Organization body mass index (BMI) ranges. CT dose index volume (CTDIvol),
      dose length product (DLP) median effective dose (ED), and size specific dose
      estimate (SSDE) were recorded. Univariable and multivariable regression analyses
      were performed to evaluate the effect of gender on radiation exposure per BMI.
      RESULTS: A total of 726 exams were included, 343 (47%) were females; mean BMI was
      similar by gender (28.6+/-6.9 kg/m(2) females vs. 29.2+/-6.3 kg/m(2) males;
      P=0.168). Median ED was 2.3 mSv (1.4-5.2) for females and 3.6 (2.5-5.9) for males
      (P<0.001). Females were exposed to less radiation by a difference in median ED of
      -1.3 mSv, CTDIvol -4.1 mGy, and SSDE -6.8 mGy (all P<0.001). After adjusting for
      BMI, patient characteristics, and gating mode, females exposure was lower by a
      median ED of -0.7 mSv, CTDIvol -2.3 mGy, and SSDE -3.15 mGy, respectively (all
      P<0.01). CONCLUSIONS: We observed a difference in radiation exposure to patients
      undergoing CCTA with the combined use of AEC-APS and breast displacement in
      female patients as compared to their BMI-matched male counterparts, with female
      patients receiving one third less exposure.

PMID- 25610803
TI  - Spotty calcification and plaque vulnerability in vivo: frequency-domain optical
      coherence tomography analysis.
AB  - BACKGROUND: Spotty calcification is a morphological characteristic of a
      vulnerable plaque phenotype. While this calcium pattern is considered an active
      process, promoted by inflammation, it is unknown whether spotty calcification
      associates with development of microstructures observed in vulnerable plaques. As
      frequency-domain optical coherence tomography (FD-OCT) enables visualization of
      microstructures associated with plaque vulnerability, we investigated the
      association between spotty calcification and plaque microstructures by using FD
      OCT. METHODS: A total of 300 patients with stable coronary artery disease (CAD),
      having clinical indication for percutaneous coronary intervention (PCI), were
      analyzed. Totally 280 non-culprit lipid plaques within the target vessel
      requiring PCI were evaluated by FD-OCT. Spotty calcification was defined as a
      presence of lesion <4 mm in length, containing an arc of calcification <90
      degrees  on FD-OCT. Plaque microstructures were compared in non-culprit lipid
      rich plaques with and without spotty calcification. RESULTS: Spotty calcification
      was observed in 39.6% of non-culprit lipid-rich plaques, with 30.6% of these
      plaques demonstrating multiple spotty calcifications. Plaques containing spotty
      calcification exhibited a greater lipid index (= averaged lipid arc * lipid
      length); 1,511.8+/-1,522.3 vs. 815.2+/-1,040.3 mm degrees , P<0.0001), thinner
      fibrous caps (89.0+/-31.6 vs. 136.5+/-32.5 um, P=0.002) and a higher prevalence
      of microchannels (45.9% vs. 17.7%, P=0.007). A significant association was
      observed between the number of spotty calcifications per plaque and fibrous cap
      thickness (r=-0.40, P=0.006). Increased number of spotty calcification was also
      associated with a higher prevalence of microchannel within plaques (P=0.01).
      CONCLUSIONS: In patients with stable CAD requiring PCI, the presence of spotty
      calcification imaged by FD-OCT was associated with features of greater plaque
      vulnerability.

PMID- 25610805
TI  - Very late outcomes of drug-eluting stents coated with biodegradable polymers:
      insights from the 5-year follow-up of the randomized PAINT trial.
AB  - BACKGROUND: Few studies have examined the very long-term outcomes after
      implantation of drug-eluting stents (DES) coated with biodegradable polymers
      (BP). This report presents the 5-year clinical follow-up of patients treated with
      BP-DES in the randomized PAINT trial. METHODS: The PAINT study is a prospective,
      multicenter randomized controlled trial that allocated 274 patients for treatment
      with two BP-DES formulations [paclitaxel-eluting stents (PES) or sirolimus
      eluting stents (SES)] or bare metal stents (BMS) in a 1:2:2 ratio, respectively.
      The primary end-point of this sub-study was defined as the composite of the major
      cardiac adverse events (MACE) cardiac death, myocardial infarction (MI) or
      ischemia-driven target vessel revascularization (TVR) at 5 years. RESULTS: The 5
      year MACE rates were different among the groups: 35.3%, 22.5% and 16.9% for BMS,
      PES and SES, respectively (P<0.05 for both DES vs. bare stent comparisons). The
      primary end-point was mainly driven by TVR: 31.8%, 14.1% and 12.2% for bare
      stents, PES and SES, respectively (P<0.05 for both DES vs. bare stent
      comparisons). The incidence of stent thrombosis (ST) was null for BMS during the
      entire follow-up. There was no definite or probable ST in the SES group after the
      second year, while one patient (1.0%) presented with a definite ST episode in the
      PES group between 4 and 5 years. CONCLUSIONS: The tested biodegradable-polymer
      coated stents releasing either paclitaxel or sirolimus, compared with same bare
      metal platform, sustained their effectiveness in reducing combined major adverse
      cardiac events and re-intervention without an increase in ST during 5 years of
      follow-up.

PMID- 25610806
TI  - Lipoprotein-associated phospholipase A2 and carotid intima-media thickness in
      individuals classified as low-risk according to Framingham.
AB  - BACKGROUND: The Framingham risk score (FRS) has long been used as a global tool
      to estimate coronary heart disease (CHD) risk, but data has shown that
      subclinical CHD may exist in those classified as low risk by FRS, and as a
      result, there is potential for misclassification. Lipoprotein-associated
      phospholipase A2 (Lp-PLA2) and carotid intima-media thickness (CIMT) are two
      emerging risk markers that are predictive of future CHD events. PURPOSE: To
      examine Lp-PLA2 and CIMT values in low risk individuals, and to explore the
      relationship between Lp-PLA2 and CIMT. METHODS: A total of 229 men and women (age
      =53+/-7 years) underwent body composition analysis, objective physical activity
      measurement, fasting blood draw to determine standard lipid values and Lp-PLA2
      mass, and CIMT measurement through ultrasound. RESULTS: For all subjects, mean
      CIMT was 0.61+/-0.1 mm, mean Lp-PLA2 mass was 197+/-45 ng/dL. A total of 19.5%
      and 34.6% of women and 4.6% and 73.8% of men were considered at elevated risk for
      CHD by CIMT (>75(th) percentile for age) and Lp-PLA2 mass (>200 ng/dL) standards,
      respectively. Both CIMT and Lp-PLA2 mass were significant independent predictors
      of each other, whereas traditional risk markers (lipids, glucose) were not.
      CONCLUSIONS: Results suggest that in those classified as low risk by FRS,
      evidence of increased CHD risk may exist through the use of newer risk markers
      like CIMT and Lp-PLA2. These emerging markers may aid in the earlier detection
      and intervention of subclinical CHD.

PMID- 25610807
TI  - Shone's anomaly: a report of one case in sub-Saharan Africa.
AB  - Shone's anomaly is a rare congenital cardiac malformation consisting of four
      obstructive lesions of the left heart and the aortic arch: a supramitral
      membrane; parachute mitral valve; subaortic stenosis; and coarctation of the
      aorta which occurs most commonly in its incomplete form. We report on a 17-year
      old male Cameroonian with a variant of shone anomaly consisting of sub-valvular
      aortic stenosis, coarctation of the aorta and parachute mitral valve. He was
      referred for the investigation of a cardiac murmur after he presented with
      shortness of breath preceded by flu like syndrome. He underwent successful
      management abroad consisting of aortic coarctation treatment by percutaneous
      angioplasty and resection of the subaortic ring by traditional surgical approach
      without any mitral valve repair. Shone's anomaly is a rare congenital heart
      disease that can be missed in low resource settings. This case raises awareness
      about this syndrome, highlights the importance of cardiac ultrasonography in
      resource limited settings and illustrates the need for comprehensive service
      frameworks to improve access and level of care and services for patients in the
      African context. 

PMID- 25610809
TI  - Synaptic incubations of another kind.

PMID- 25610808
TI  - Anatomical art.

PMID- 25610810
TI  - Challenges of clinical trial design for targeted agents against pediatric
      leukemias.
AB  - The past 40 years have seen significant improvements in both event-free and
      overall survival for children with acute lymphoblastic and acute myeloid leukemia
      (ALL and AML, respectively). Serial national and international clinical trials
      have optimized the use of conventional chemotherapeutic drugs and, along with
      improvements in supportive care that have enabled the delivery of more intensive
      regimens, have been responsible for the major improvements in patient outcome
      seen over the past few decades. However, the benefits of dose intensification
      have likely now been maximized, and over the same period, the identification of
      new cytotoxic drugs has been limited. Therefore, challenges remain if survival is
      to be improved further. In pediatric ALL, 5-year-survival rates of over 85% have
      been achieved with risk-stratified therapy, but a notable minority of patients
      will still not be cured. In pediatric AML, different challenges remain. A slower
      improvement in overall survival has taken place in this patient population.
      Despite the obvious morphological heterogeneity of AML blasts, biological
      stratification is comparatively limited, and translation into risk-stratified
      therapeutic approaches has only best characterized by the use of retinoic acid
      for t(15;17)-positive AML. Even where prognostic markers have been identified,
      limited therapeutic options or multi-drug resistance of AML blasts has limited
      the impact on patient benefit. For both, the acute morbidities of current
      treatment remain significant and may be life-threatening alone. In addition, the
      Childhood Cancer Survivor Study (CCSS) highlighted many leukemia survivors
      develop one or more chronic medical conditions attributable to treatment (1, 2).
      As the biology of leukemogenesis has become better understood, key molecules and
      intracellular pathways have been identified that offer the possibility of
      targeting directly the leukemia cells while sparing normal cells. Consequently,
      there is now a drive to develop novel leukemia-specific or "targeted" therapies.
      These new classes of drugs will have mechanisms of action, toxicities, and
      therapeutic indices quite different from conventional cytotoxic drugs previously
      encountered, thus rendering current clinical trial methodologies inappropriate.
      Clinical trial methods will need to be adapted to accommodate these features of
      these new classes of drugs. This review will address the challenges and some of
      the techniques for developing clinical trials for targeted therapies. 

PMID- 25610812
TI  - Coxiella burnetii lipopolysaccharide blocks p38alpha-MAPK activation through the
      disruption of TLR-2 and TLR-4 association.
AB  - To survive in macrophages, Coxiella burnetii hijacks the activation pathway of
      macrophages. Recently, we have demonstrated that C. burnetii, via its
      lipopolysaccharide (LPS), avoids the activation of p38alpha-MAPK through an
      antagonistic engagement of Toll-like receptor (TLR)-4. We investigated the fine
      tuned mechanism leading to the absence of activation of the p38alpha-MAPK despite
      TLR-4 engagement. In macrophages challenged with LPS from the avirulent variants
      of C. burnetii, TLR-4 and TLR-2 co-immunoprecipitated. This association was
      absent in cells challenged by the LPS of pathogenic C. burnetii. The disruption
      makes TLRs unable to signal during the recognition of the LPS of pathogenic C.
      burnetii. The disruption of TLR-2 and TLR-4 was induced by the re-organization of
      the macrophage cytoskeleton by C. burnetii LPS. Interestingly, blocking the actin
      cytoskeleton re-organization relieved the disruption of the association TLR-2/TLR
      4 by pathogenic C. burnetii and rescued the p38alpha-MAPK activation by C.
      burnetii. We elucidated an unexpected mechanism allowing pathogenic C. burnetii
      to avoid macrophage activation by the disruption of the TLR-2 and TLR-4
      association. 

PMID- 25610813
TI  - Prevalence of metabolic syndrome in patients with minor beta thalassemia and its
      related factors: a cross-sectional study.
AB  - BACKGROUND: Atherosclerotic disorders, hypertension and lipid profile alterations
      are of a lower prevalence in patients with minor beta thalassemia. On the other
      hand, nowadays, metabolic syndrome is considered as one of the major risk factors
      of developing cardiovascular diseases. Therefore, the present study was performed
      to determine the prevalence of metabolic syndrome in patients with minor beta
      thalassemia. METHODS: In this case-control study, body length, weight and waist
      circumference, blood pressure, fasting blood sugar [FBS], triglyceride,
      cholesterol, HDL, and LDL levels were determined in 150 patients with minor beta
      thalassemia and 300 healthy individuals as control group [matched based on age
      and sex]. The prevalence of metabolic syndrome was calculated based on ATPIII
      criteria. Data were analyzed through SPSS16 software package. RESULTS: The
      prevalence of metabolic syndrome was 12.7% in the thalassemia group and 36.7% in
      the control group [p < 0.0001]. In the patient group, 3 ones [8.3%] of those with
      metabolic syndrome were male and 16 ones [14%] were female [p = 0.5]. Mean age of
      patients with metabolic syndrome was 39.4 +/- 8.5 years and mean age of those
      without metabolic syndrome was 36.4 +/- 7.8 years [p = 0.1]. Mean BMI of those
      with metabolic syndrome was 31.3 +/- 4.1 kg/m(2) and that of those without
      metabolic syndrome was 24.2 +/- 4.4 kg/m(2) [p < 0.0001]. CONCLUSIONS: The
      obtained results show lower prevalence of metabolic syndrome in patients with
      minor thalassemia. Moreover, the prevalence of metabolic syndrome in patients
      with minor thalassemia showed no relationship with sex and age and these patients
      had just higher BMI.

PMID- 25610811
TI  - Endoplasmic reticulum chaperones and their roles in the immunogenicity of cancer
      vaccines.
AB  - The endoplasmic reticulum (ER) is a major site of passage for proteins en route
      to other organelles, to the cell surface, and to the extracellular space. It is
      also the transport route for peptides generated in the cytosol by the proteasome
      into the ER for loading onto major histocompatibility complex class I (MHC I)
      molecules for eventual antigen presentation at the cell surface. Chaperones
      within the ER are critical for many of these processes; however, outside the ER
      certain of those chaperones may play important and direct roles in immune
      responses. In some cases, particular ER chaperones have been utilized as vaccines
      against tumors or infectious disease pathogens when purified from tumor tissue or
      recombinantly generated and loaded with antigen. In other cases, the cell surface
      location of ER chaperones has implications for immune responses as well as
      possible tumor resistance. We have produced heat-shock protein/chaperone protein
      based cancer vaccines called "chaperone-rich cell lysate" (CRCL) that are
      conglomerates of chaperones enriched from solid tumors by an isoelectric focusing
      technique. These preparations have been effective against numerous murine tumors,
      as well as in a canine with an advanced lung carcinoma treated with autologous
      CRCL. We also published extensive proteomic analyses of CRCL prepared from human
      surgically resected tumor samples. Of note, these preparations contained at least
      10 ER chaperones and a number of other residents, along with many other
      chaperones/heat-shock proteins. Gene ontology and network analyses utilizing
      these proteins essentially recapitulate the antigen presentation pathways and
      interconnections. In conjunction with our current knowledge of cell
      surface/extracellular ER chaperones, these data collectively suggest that a
      systems-level view may provide insight into the potent immune stimulatory
      activities of CRCL with an emphasis on the roles of ER components in those
      processes. 

PMID- 25610815
TI  - Cost analysis of adjuvant management strategies in early stage (stage I)
      testicular seminoma.
AB  - BACKGROUND: Acceptable post-orchiectomy adjuvant therapy strategies for stage I
      seminoma patients include surveillance, para-aortic radiation therapy (RT), dog
      leg RT, and a single cycle of carboplatin. The required follow-up recommendations
      were amended by the National Comprehensive Cancer Network (NCCN) in 2012. Given a
      cause-specific survival of nearly 100%, a closer analysis of the reimbursement
      for each treatment strategy is warranted. METHODS: NCCN guidelines were used to
      design treatment plans for each acceptable adjuvant treatment strategy. Follow-up
      charges were generated for 10 years based on 2012 (version 1.2012; unchanged in
      current version 1.2013) and 2011 NCCN (version 2.2011) surveillance
      recommendations. The 2012 Medicare reimbursement rates were used to calculate
      each treatment strategy and incremental cost-effectiveness ratios to compare the
      treatment options. RESULTS: Under the current NCCN follow-up recommendations, the
      total reimbursements generated over 10 years of surveillance, para-aortic RT, dog
      leg RT, and carboplatin were $10,643, $11,678, $9,662, and $10,405, respectively.
      This is compared with the reimbursements as per the 2011 NCCN recommendations:
      $20,986, $11,517, $9,394, and $20,365 respectively. Factoring the rates of
      relapse into a salvage model, observation was found to be more costly and less
      effective ($-1,831, $-7,318, $-7,010) in the adjuvant management of stage I
      seminoma patients. CONCLUSION: Based on incremental cost-effectiveness ratios,
      para-aortic RT, dog-leg RT, and carboplatin are cost-effective options for the
      treatment of stage I seminoma when compared with observation; however,
      surveillance could potentially spare as many as 80%-85% of men diagnosed with
      stage I seminoma from additional therapy after radical inguinal orchiectomy. Such
      cost and reimbursement analyses are becoming increasingly relevant, but are not
      meant to usurp sound clinical judgment. Further studies are required to validate
      these findings.

PMID- 25610816
TI  - Evolution of exercise rehabilitation.

PMID- 25610814
TI  - Prevalence of obesity and overweight in adults and children in Iran; a systematic
      review.
AB  - BACKGROUND: Obesity is one of the most important underlying risk factors for
      chronic disease. Dramatically increasing and following complication of obesity
      should be alerted to health politicians and practitioners to prevent associated
      health risks. This review aimed to give a better insight into the prevalence of
      obesity and overweight in different areas of Iran. METHOD: All published internal
      (SID, Irandoc, Iranmedex), and international (Web of Knowledge, Pubmed, Scopus)
      source studies, reported the prevalence of overweight/obesity among normal
      population samples, during Jan 2005 through Jan 2014, were assessed in this
      review. Paper selection processes were done by two researchers separately.
      Studies which met the eligible criteria were included in this review. RESULT: One
      hundred ninety three eligible studies enter into our review. Of 193 final
      selected studies, 86 (15 national, 71 sub national) of them were reported the
      prevalence of obesity/overweight in adult, and 107 studies (11 national, 96 sub
      national) in under-18 by individual. The range of overweight and obesity
      prevalence in national studies in adult, was 27.0-38.5 (95% CI: 26.8-27.1, 37.2
      39.8), and 12.6-25.9 (95% CI: 12.2-13.0, 24.9-26.8), separately. In under-18 the
      range of overweight and obesity prevalence in national studies were 5.0-13.5 (95%
      CI: 4.5-5.5, 13.4-13.6), and 3.2-11.9 (95% CI: 3.0-3.4, 11.3-12.4). CONCLUSION:
      Obesity as an important public health problem has been discussed in recent few
      decades worldwide. Although the national reported prevalence of obesity in Iran
      was not considerably diverse, but remarkable differences were seen in the sub
      national prevalence which must be noticed more in political health programs
      especially among women and children.

PMID- 25610817
TI  - Differential susceptibility on myosin heavy chain isoform following eccentric
      induced muscle damage.
AB  - Based on myosin heavy chain (MHC) isoform, human skeletal muscle fibers can be
      categorized into three fiber types, type I, IIa, IIx fibers, and each fiber type
      has different characteristics. Typical characteristics are difference in force
      production, shortening velocity, and fatigue resistance. When the muscle is
      contract and stretched by a force that is greater than the force generated by the
      muscle, contraction-induced muscle damage frequently occurs. Several experimental
      models involving both human and animal have considered the susceptibility of
      different muscle fiber type and part of muscles to eccentric induced muscle
      damage. General consensus is a greater susceptibility of fast-twitch fiber or
      type II fiber to damage following eccentric contractions. However, the results
      from these previous efforts were not enough to conclude the susceptibility
      between each individual fiber types after eccentric contraction. Therefore, the
      purpose of this review is to explore detail limitation and interpretation of
      previous studies, and review the recent study that eliminated the prior
      limitations, such as strain magnitude, lengthening velocity, fiber type
      heterogeneity, and muscle architecture issue. 

PMID- 25610818
TI  - A review of nutritional intervention on delayed onset muscle soreness. Part I.
AB  - This review is focused on the effect of nutritional intervention on delayed onset
      muscle soreness (DOMS) that occurs after exercise. In general, high force
      eccentric contractions and/or unaccustomed exercise result in DOMS attributed to
      reduction in performance such as muscle strength and range of motion (ROM) for
      both athletes and non-athletes. Nutritional intervention is one of the preventive
      or therapeutic ways to reduce DOMS. Previous research studies have suggested the
      following nutrition intervention: caffeine, omega-3 fatty acids, taurine,
      polyphenols, and so on. Nutritional intervention with these nutrients before and
      after exercise was reported to be effective in reducing DOMS. These nutritional
      interventions have also been reported to affect inflammatory responses and
      oxidative stress leading to DOMS reduction. However, other studies have reported
      that these nutritional interventions have no effect on DOMS. It is suggested that
      intake of proper nutrition intervention can effectively reduce DOMS after
      exercise and quickly help an athlete return to exercise or training program. In
      addition, nutritional intervention may help both athletes and non-athletes who
      engage in physical therapy or rehabilitative programs after surgery or any
      injurious events. 

PMID- 25610819
TI  - The effect of Alexander technique training program: A qualitative study of
      ordinary behavior application.
AB  - The purpose of this study was to configure and apply the Alexander technique
      training program and assess the effect of program through physical, emotional and
      behavioral aspects. To achieve the research aims, qualitative research method had
      been conducted, subjecting 8 people, who were participating in Alexander
      Technique training program for this study. The study used focus group interview
      method for collecting date and employed for the interview method by mixing the
      semi-structured and unstructured questionnaire. The results were followings.
      First, one could develop body awareness and body consciousness through
      experiencing lived bodily sensation. Second, from Alexander Technique training
      program, people experienced psycho & physical's equilibrium. Third, one could
      change not only the manner of use of body but also the attitude to the life from
      conscious attention to daily ordinary movement. The results provided empirical
      evidence of Alexander Technique training program's functions in terms of
      physical, emotional and behavioral aspect through the process of consciousness
      control from lived body education. 

PMID- 25610820
TI  - The effects of ketogenic diet on oxidative stress and antioxidative capacity
      markers of Taekwondo athletes.
AB  - The purpose of this study was to investigate the effects of the ketogenic diet
      through 3 weeks on oxidative stress and antioxidative capacity markers in
      Taekwondo athletes. The participants selected for this research were 18 high
      school taekwondo contestants aged 15-18 who had at least 5 yr of career as
      contestant. The subjects were randomly assigned to the ketogenic diet (KD) group
      and the Non ketogenic diet (NDK) group. Body composition and oxidative stress and
      antioxidative capacity markers (LDH, MDA, ROS, HDL, and SOD) were analysed before
      and after 3 weeks of ketogenic diet. No significant difference was found between
      the groups in body composition, ROS and SOD level. The KD group showed an
      elevated HDL level and NKD group showed an elevated LDH and MDA level after
      ketogenic diet by 3 weeks. This result suggests that weight loss by 3 weeks of
      calorie restriction and exercise can cause oxidative stress, and that ketogenic
      diet can be effective for preventing it. It could also be inferred that ketogenic
      diet can be effective for increasing blood antioxidative capacity. 

PMID- 25610821
TI  - The relationship between attention deficit hyperactivity disorder and health
      related physical fitness in university students.
AB  - College students with a tendency toward attention deficit/hyperactivity disorder
      (ADHD) tend to act impulsively because they cannot control their behavior. They
      display low academic achievement and insufficient social skills, and are at high
      risk for alcoholism and drug abuse. Although various intervention methods have
      been used to reduce ADHD tendency (e.g., improving physical fitness and
      participating in sports and exercise), there are few studies on the relationship
      between ADHD and health-related physical fitness. Accordingly, this study
      explored the relationship between ADHD symptoms in college students and physical
      fitness. We measured health-related physical fitness and ADHD in 86 male college
      students using a self-report rating scale. The results showed the following.
      First, a significant relationship was found between ADHD tendency and
      inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional
      lability, and abdominal fat. Push-ups were associated with ADHD tendency and the
      inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional
      lability, and problems with self-concept subtests. Grip strength was
      significantly related to inattention/memory problems. Second, risk factors for
      ADHD tendency significantly increased for male college students with low muscular
      strength and endurance relative to those with greater muscular strength and
      endurance. Risk factors also significantly increased for male college students
      with high rates of abdominal obesity. 

PMID- 25610822
TI  - Osteoprotective effect of extract from Achyranthes japonica in ovariectomized
      rats.
AB  - This study was carried out to investigate the effects of the Achyrantes japonica
      (A. japonica) extract on serum level of hormones from osteoporosis induced
      ovariectomized rats. Two month-old rats were ovariectomized (OVX), remained
      untreated for 8 weeks, and were subsequently administered A. japonica (300 mg/kg)
      every day for 8 weeks. We examined the effects of treated A. japonica every 10
      days on ovariectomy-related changes in Insulin-like Growth Factors (IGF), Insulin
      like Growth Factor binding protein-3 (IGBF-3), Estrogen, Calcium, and Phosporus.
      After 8 weeks, the serum levels of IGF-I, -II, and IGFBP-3 were higher presented
      as compared to the other two groups (P< 0.05), in the A. japonica extract
      treatment on OVX rats. Bone alkaline phosphatase levels were increased through A.
      japonica extract treatment in OVX rats compared to the other two groups. There
      were no differences between OVX and A. japonica extract treated OVX rats in serum
      levels of estrogen, but estrogen levels for the sham group were higher than for
      the other two groups. A. japonica extract is increased to serum levels of IGFs
      and IGFBP-3 of osteoporosis induced by ovariectomized rats. Thus, the results
      reveal that the A. japonica extract is a possible role for improvement of
      osteoporosis induced-ovariectomized rats and has a great potential as an
      alternative tool for the treatment of osteoporosis. 

PMID- 25610823
TI  - Modified laparoscopic intravesical nonrefluxing ureteral reimplantation with
      psoas hitch using a submucosal tunneling.
AB  - We aimed to study the safety and efficacy of the cystoscopy-assisted nonrefluxing
      ureteral reimplantation technique using submucosal tunneling during laparoscopic
      ureteroneocystostomy (UNC) with a psoas hitch in patients with distal ureter
      stricture after gynecologic surgery. We reviewed six female patients who
      underwent gynecological surgeries. All patients showed persistent postoperative
      distal ureter stricture or obstruction. These patients underwent laparoscopic
      nonrefluxing UNC with a psoas hitch using a submucosal tunneling technique
      combined with cystoscopy at our institute. They had corrective surgery at an
      average of 13.3 weeks after ureteral injury. The short-term success was confirmed
      either by voiding cystourethrography (VCU) or by diuretic isotope renal scan (MAG
      3) conducted 3 months after the operation. None of the patients showed evidence
      of postoperative stricture at the reimplanted site and reflux on either MAG-3
      renal scan or VCU. None of the patients showed major or minor complications
      during follow-up. It is safe and feasible to perform the laparoscopic
      nonrefluxing UNC with a psoas hitch using a submucosal tunneling technique
      combined with cystoscopy for ureteral stricture. 

PMID- 25610824
TI  - Association of BID SNPs (rs8190315 and rs2072392) and clinical features of benign
      prostate hyperplasia in Korean population.
AB  - Exercise has beneficial effect on cancer apoptosis and benign prostatic
      hyperplasia (BPH). The BH3 interacting domain death agonist (BID) gene expression
      is associated with apoptosis or cell proliferation. In this study, we
      investigated the association between BID single nucleotide polymorphisms (SNPs)
      and the development, prostate volume, and international prostate symptom score
      (IPSS) of BPH. In 222 BPH males and 214 controls, two SNPs in BID [rs8190315
      (Ser56Gly), and rs2072392 (Asp106Asp)] were genotyped and analyzed using multiple
      logistic regression models. In the result, the genotype and allele frequencies of
      rs8190315 and rs2072392 were not associated with BPH development or IPSS,
      however, the allele frequencies [odd ratio (OR)= 1.90, 95% confidence interval
      (CI)= 1.07-3.41, P= 0.03] and genotype frequencies (in dominant model, OR= 1.94,
      95% CI= 1.01-3.74, P= 0.42) of rs8190315, and the genotype frequencies of
      rs2072392 (in dominant model, OR= 1.94, 95% CI= 1.01-3.74, P= 0.42) were
      associated with increased prostate volume. We propose that rs8190315 and
      rs2072392 of BID may contribute to the disease severity of BPH. 

PMID- 25610825
TI  - Gender Dysphoria in 46,XX Persons with Adrenogenital Syndrome Raised as Females:
      An Addendum.

PMID- 25610826
TI  - Rheumatic Fever prevention program: long-term evolution and outcomes.
AB  - This investigation aims to analyze the profile of long-term evolution of
      rheumatic fever in children and adolescents and outcomes after the control of
      recurrences. The cohort involved 702 patients followed from 1.3 to 16.9 years
      covering the two periods, before and after the implementation of a prevention
      program. Besides the establishment of the Reference Center in the State of Minas
      Gerais and the implementation of strategies to promote the compliance to
      prophylaxis, a project for education of health professionals was carried out in
      23 cities. In addition to the clinical and epidemiological profile, the severity
      of the disease was analyzed. Mixed lesions were found in 27.1%, valvar
      regurgitation in 72.9%, and complete regression of the valvar lesions was seen in
      34.4% of the patients, mostly presenting mild dysfunctions. The recurrence rate
      per patient-year was 0.058 and out of a total of 85 recurrences, 21.4% occurred
      in the first and 7.5% in the second period. More severe degrees of carditis and
      significant valvar sequels presented a higher prevalence in patients with
      recurrences. The comparative analysis between the two periods showed no changes
      regarding the age at the primary attack, gender, type, and site of valvar lesions
      and affected joints; however, important modifications in the indices of severity
      were observed after the control of recurrences. A significant decrease in the
      prevalence of severe carditis, obstructive valvar sequels, hospital admissions,
      surgical approach, and deaths was seen. This investigation showed that although
      the clinical profile of presentation remains unchanged, the control of repeated
      attacks can improve the morbimortality rates. In this context, the secondary
      prophylaxis should be the first priority in the control of the disease in
      developing countries, taking into account the difficulties found for effective
      primordial and primary prevention. 

PMID- 25610827
TI  - Experimental models of early exposure to alcohol: a way to unravel the
      neurobiology of mental retardation.

PMID- 25610828
TI  - A modified rabbit ulna defect model for evaluating periosteal substitutes in bone
      engineering: a pilot study.
AB  - The present work defines a modified critical size rabbit ulna defect model for
      bone regeneration in which a non-resorbable barrier membrane was used to separate
      the radius from the ulna to create a valid model for evaluation of tissue
      engineered periosteal substitutes. Eight rabbits divided into two groups were
      used. Critical defects (15 mm) were made in the ulna completely eliminating
      periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester
      urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a
      tissue-engineered periosteal substitute (group Ib). For group II, an expanded
      polytetrafluoroethylene (e-PTFE) (GORE-TEX((r))) membrane was inserted around the
      radius then the defects received either scaffold alone (group IIa) or scaffold
      wrapped with periosteal substitute (group IIb). Animals were euthanized after 12
      16 weeks, and bone regeneration was evaluated by radiography, computed
      microtomography (MUCT), and histology. In the first group, we observed formation
      of radio-ulnar synostosis irrespective of the treatment. This was completely
      eliminated upon placement of the e-PTFE (GORE-TEX((r))) membrane in the second
      group of animals. In conclusion, modification of the model using a non-resorbable
      e-PTFE membrane to isolate the ulna from the radius was a valuable addition
      allowing for objective evaluation of the tissue-engineered periosteal substitute.

PMID- 25610829
TI  - Pathogen security-help or hindrance?
AB  - Events over the past 15 years have resulted in the promulgation of regulations in
      the United States to enhance biosecurity by restricting the access to pathogens
      and toxins (i.e., biological select agents and toxins [BSATs]), which pose a
      severe threat to human being, animal, or plant health or to animal or plant
      products, to qualified institutions, laboratories, and scientists. These
      regulations also reduce biosafety concerns by imposing specific requirements on
      laboratories working with BSATs. Furthermore, they provide a legal framework for
      prosecuting someone who possesses a BSAT illegally. With the implementation of
      these regulations has come discussion in the scientific community about the
      potential of these regulations to affect the cost of doing BSAT research, hamper
      research and international collaborations, or whether it would stop someone with
      a microbiological background from isolating many of the select agents from
      nature. 

PMID- 25610831
TI  - A free-knot spline modeling framework for piecewise linear logistic regression in
      complex samples with body mass index and mortality as an example.
AB  - This paper details the design, evaluation, and implementation of a framework for
      detecting and modeling nonlinearity between a binary outcome and a continuous
      predictor variable adjusted for covariates in complex samples. The framework
      provides familiar-looking parameterizations of output in terms of linear slope
      coefficients and odds ratios. Estimation methods focus on maximum likelihood
      optimization of piecewise linear free-knot splines formulated as B-splines.
      Correctly specifying the optimal number and positions of the knots improves the
      model, but is marked by computational intensity and numerical instability. Our
      inference methods utilize both parametric and nonparametric bootstrapping. Unlike
      other nonlinear modeling packages, this framework is designed to incorporate
      multistage survey sample designs common to nationally representative datasets. We
      illustrate the approach and evaluate its performance in specifying the correct
      number of knots under various conditions with an example using body mass index
      (BMI; kg/m2) and the complex multi-stage sampling design from the Third National
      Health and Nutrition Examination Survey to simulate binary mortality outcomes
      data having realistic nonlinear sample-weighted risk associations with BMI. BMI
      and mortality data provide a particularly apt example and area of application
      since BMI is commonly recorded in large health surveys with complex designs,
      often categorized for modeling, and nonlinearly related to mortality. When
      complex sample design considerations were ignored, our method was generally
      similar to or more accurate than two common model selection procedures, Schwarz's
      Bayesian Information Criterion (BIC) and Akaike's Information Criterion (AIC), in
      terms of correctly selecting the correct number of knots. Our approach provided
      accurate knot selections when complex sampling weights were incorporated, while
      AIC and BIC were not effective under these conditions.

PMID- 25610832
TI  - Editors' page.

PMID- 25610833
TI  - Addressing cardiovascular inequalities among indigenous Australians.

PMID- 25610830
TI  - Exercise and NO production: relevance and implications in the cardiopulmonary
      system.
AB  - This article reviews the existing knowledge about the effects of physical
      exercise on nitric oxide (NO) production in the cardiopulmonary system. The
      authors review the sources of NO in the cardiopulmonary system; involvement of
      three forms of NO synthases (eNOS, nNOS, and iNOS) in exercise physiology;
      exercise-induced modulation of NO and/or NOS in physiological and
      pathophysiological conditions in human subjects and animal models in the absence
      and presence of pharmacological modulators; and significance of exercise-induced
      NO production in health and disease. The authors suggest that physical activity
      significantly improves functioning of the cardiovascular system through an
      increase in NO bioavailability, potentiation of antioxidant defense, and decrease
      in the expression of reactive oxygen species-forming enzymes. Regular physical
      exercises are considered a useful approach to treat cardiovascular diseases.
      Future studies should focus on detailed identification of (i) the exercise
      mediated mechanisms of NO exchange; (ii) optimal exercise approaches to improve
      cardiovascular function in health and disease; and (iii) physical effort
      thresholds. 

PMID- 25610834
TI  - The blue girl.

PMID- 25610835
TI  - Clinical and molecular classification of cardiomyopathies.
AB  - The term "cardiomyopathies" was used for the first time 55 years ago, in 1957.
      Since then awareness and knowledge of this important and complex group of heart
      muscle diseases have improved substantially. Over these past five decades a large
      number of definitions, nomenclature and schemes, have been advanced by experts
      and consensus panel, which reflect the fast and continued advance of the
      scientific understanding in the field. Cardiomyopathies are a heterogeneous group
      of inherited myocardial diseases, which represent an important cause of
      disability and adverse outcome. Although considered rare diseases, the overall
      estimated prevalence of all cardiomyopathies is at least 3% in the general
      population worldwide. Furthermore, their recognition is increasing due to
      advances in imaging techniques and greater awareness in both the public and
      medical community. Cardiomyopathies represent an ideal translational model of
      integration between basic and clinical sciences. A multidisciplinary approach is
      therefore essential in order to ensure their correct diagnosis and management. In
      the present work, we aim to provide a concise overview of the historical
      background, genetic and phenotypic spectrum and evolving concepts leading to the
      various attempts of cardiomyopathy classifications produced over the decades. 

PMID- 25610836
TI  - Hypertrophic cardiomyopathy: The first century 1869-1969.

PMID- 25610837
TI  - Molecular genetics made simple.
AB  - Genetics have undoubtedly become an integral part of biomedical science and
      clinical practice, with important implications in deciphering disease
      pathogenesis and progression, identifying diagnostic and prognostic markers, as
      well as designing better targeted treatments. The exponential growth of our
      understanding of different genetic concepts is paralleled by a growing list of
      genetic terminology that can easily intimidate the unfamiliar reader. Rendering
      genetics incomprehensible to the clinician however, defeats the very essence of
      genetic research: its utilization for combating disease and improving quality of
      life. Herein we attempt to correct this notion by presenting the basic genetic
      concepts along with their usefulness in the cardiology clinic. Bringing genetics
      closer to the clinician will enable its harmonious incorporation into clinical
      care, thus not only restoring our perception of its simple and elegant nature,
      but importantly ensuring the maximal benefit for our patients. 

PMID- 25610839
TI  - Familial dilated cardiomyopathy: Current challenges and future directions.

PMID- 25610838
TI  - The expanding role of epigenetics.

PMID- 25610840
TI  - Pattern and degree of left ventricular remodeling following a tailored surgical
      approach for hypertrophic obstructive cardiomyopathy.
AB  - Background The role of a tailored surgical approach for hypertrophic
      cardiomyopathy (HCM) on regional ventricular remodelling remains unknown. The
      aims of this study were to evaluate the pattern, extent and functional impact of
      regional ventricular remodelling after a tailored surgical approach. Methods From
      2005 to 2008, 44 patients with obstructive HCM underwent tailored surgical
      intervention. Of those, 14 were ineligible for cardiac magnetic resonance (CMR)
      studies. From the remainder, 14 unselected patients (42+/-12 years) underwent pre
      and post-operative CMR studies at a median 12 months post-operatively (range 4
      37 months). Regional changes in left ventricular (LV) thickness as well as global
      LV function following surgery were assessed using CMR Tools (London, UK). Results
      Pre-operative mean echocardiographic septal thickness was 21+/-4 mm and mean LV
      outflow gradient was 69+/-32 mmHg. Following surgery, there was a significant
      degree of regional regression of LV thickness in all segments of the LV, ranging
      from 16% in the antero-lateral midventricular segment to 41% in the anterior
      basal segment. Wall thickening was significantly increased in basal segments but
      showed no significant change in the midventricular or apical segments. Globally,
      mean indexed LV mass decreased significantly after surgery (120+/-29g/m2 versus
      154+/-36g/m2; p<0.001). There was a trend for increased indexed LV end-diastolic
      volume (70+/-13 mL versus 65+/-11 mL; p=0.16) with a normalization of LV ejection
      fraction (68+/-7% versus 75+/-9%; p<0.01). Conclusion Following a tailored
      surgical relief of outflow obstruction for HCM, there is a marked regional
      reverse LV remodelling. These changes could have a significant impact on overall
      ventricular dynamics and function. 

PMID- 25610843
TI  - Transcatheter aortic valve implantation.

PMID- 25610842
TI  - Endomyocardial fibrosis: A form of endemic restrictive cardiomyopathy.
AB  - Endomyocardial fibrosis is a form of endemic restrictive cardiomyopathy that
      affects mainly children and adolescents, and is geographically restricted to some
      poor areas of Africa, Latin America and Asia. It is a condition with high
      morbidity and mortality, for which no effective therapy is available. Although
      several hypotheses have been proposed as triggers or causal factors for the
      disease, none are able to explain the occurrence of the disease worldwide. In
      endemic areas of Africa endomyocardial fibrosis is as common a cause of heart
      failure as rheumatic heart disease, accounting for up to 20% of cases of heart
      failure and imposes a considerable burden to the communities and the health
      systems. However, due to lack of resources for research in these areas, the exact
      epidemiology, etiology and pathogenesis remain unknown, and the natural history
      is incompletely understood. We here review the main aspects of epidemiology,
      natural history, clinical picture and management of endomyocardial fibrosis,
      proposing new ways to increase research into this challenging and neglected
      cardiovascular disease. 

PMID- 25610844
TI  - Endo-aneurysmorrhaphy of a giant aneurysm of the subclavian vein.
AB  - Venous aneurysms are relatively rare anomalies which can affect different parts
      of the vascular system. Diagnosis and management of this condition could pose
      important problems. We here report a giant false aneurysm of the subclavian vein
      with emphasis on the thought process that determined the management strategy. 

PMID- 25610841
TI  - Heart failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a
      major cause of cardiovascular morbidity and mortality. Contrary to initial
      beliefs, HFpEF is now known to be as common as heart failure with reduced
      ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a
      prevalence that has been steadily rising over the past two decades, it is very
      likely that HFpEF will represent the dominant heart failure phenotype over the
      coming few years. The scarcity of trials in this semi-discrete form of heart
      failure and lack of unified enrolment criteria in the studies conducted to date
      might have contributed to the current absence of specific therapies.
      Understanding the epidemiological, pathophysiological and molecular differences
      (and similarities) between these two forms of heart failure is cornerstone to the
      development of targeted therapies. Carefully designed studies that adhere to
      unified diagnostic criteria with the recruitment of appropriate controls and
      adoption of practical end-points are urgently needed to help identify effective
      treatment strategies. 

PMID- 25610845
TI  - Minimally invasive procedures on the lumbar spine.
AB  - Degenerative disease of the lumbar spine is a common and increasingly prevalent
      condition that is often implicated as the primary reason for chronic low back
      pain and the leading cause of disability in the western world. Surgical
      management of lumbar degenerative disease has historically been approached by way
      of open surgical procedures aimed at decompressing and/or stabilizing the lumbar
      spine. Advances in technology and surgical instrumentation have led to minimally
      invasive surgical techniques being developed and increasingly used in the
      treatment of lumbar degenerative disease. Compared to the traditional open spine
      surgery, minimally invasive techniques require smaller incisions and decrease
      approach-related morbidity by avoiding muscle crush injury by self-retaining
      retractors, preventing the disruption of tendon attachment sites of important
      muscles at the spinous processes, using known anatomic neurovascular and muscle
      planes, and minimizing collateral soft-tissue injury by limiting the width of the
      surgical corridor. The theoretical benefits of minimally invasive surgery over
      traditional open surgery include reduced blood loss, decreased postoperative pain
      and narcotics use, shorter hospital length of stay, faster recover and quicker
      return to work and normal activity. This paper describes the different minimally
      invasive techniques that are currently available for the treatment of
      degenerative disease of the lumbar spine. 

PMID- 25610846
TI  - Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to
      arterial renal resistances.
AB  - Chronic kidney disease and its worsening are recurring conditions in chronic
      heart failure (CHF) which are independently associated with poor patient outcome.
      The heart and kidney share many pathophysiological mechanisms which can determine
      dysfunction in each organ. Cardiorenal syndrome is the condition in which these
      two organs negatively affect each other, therefore an accurate evaluation of
      renal function in the clinical setting of CHF is essential. This review aims to
      revise the parameters currently used to evaluate renal dysfunction in CHF with
      particular reference to the usefulness and the limitations of biomarkers in
      evaluating glomerular dysfunction and tubular damage. Moreover, it is reported
      the possible utility of renal arterial resistance index (a parameter associated
      with abnormalities in renal vascular bed) for a better assesment of kidney
      disfunction. 

PMID- 25610847
TI  - Anthrax: A disease of biowarfare and public health importance.
AB  - Bioterrorism has received a lot of attention in the first decade of this century.
      Biological agents are considered attractive weapons for bioterrorism as these are
      easy to obtain, comparatively inexpensive to produce and exhibit widespread fear
      and panic than the actual potential of physical damage. Bacillus anthracis (B.
      anthracis), the etiologic agent of anthrax is a Gram positive, spore forming, non
      motile bacterium. This is supposed to be one of the most potent BW agents because
      its spores are extremely resistant to natural conditions and can survive for
      several decades in the environment. B. anthracis spores enter the body through
      skin lesion (cutaneous anthrax), lungs (pulmonary anthrax), or gastrointestinal
      route (gastrointestinal anthrax) and germinate, giving rise to the vegetative
      form. Anthrax is a concern of public health also in many countries where
      agriculture is the main source of income including India. Anthrax has been
      associated with human history for a very long time and regained its popularity
      after Sept 2001 incidence in United States. The present review article describes
      the history, biology, life cycle, pathogenicity, virulence, epidemiology and
      potential of B. anthracis as biological weapon. 

PMID- 25610848
TI  - Enamel microabrasion: An overview of clinical and scientific considerations.
AB  - Superficial stains and irregularities of the enamel are generally what prompt
      patients to seek dental intervention to improve their smile. These stains or
      defects may be due to hypoplasia, amelogenesis imperfecta, mineralized white
      spots, or fluorosis, for which enamel microabrasion is primarily indicated.
      Enamel microabrasion involves the use of acidic and abrasive agents, such as with
      37% phosphoric acid and pumice or 6% hydrochloric acid and silica, applied to the
      altered enamel surface with mechanical pressure from a rubber cup coupled to a
      rotatory mandrel of a low-rotation micromotor. If necessary, this treatment can
      be safely combined with bleaching for better esthetic results. Recent studies
      show that microabrasion is a conservative treatment when the enamel wear is
      minimal and clinically imperceptible. The most important factor contributing to
      the success of enamel microabrasion is the depth of the defect, as deeper, opaque
      stains, such as those resulting from hypoplasia, cannot be resolved with
      microabrasion, and require a restorative approach. Surface enamel alterations
      that result from microabrasion, such as roughness and microhardness, are easily
      restored by saliva. Clinical studies support the efficacy and longevity of this
      safe and minimally invasive treatment. The present article presents the clinical
      and scientific aspects concerning the microabrasion technique, and discusses the
      indications for and effects of the treatment, including recent works describing
      microscopic and clinical evaluations. 

PMID- 25610849
TI  - Recent advances in the HER2 targeted therapy of gastric cancer.
AB  - Recent advances in molecular targeted therapies, including targeting human
      epidermal growth factor receptor 2 (HER2), had a major forward step in the
      therapy for gastric cancer patients. Application of HER2-targeted therapies, in
      particular trastuzumab in combination with chemotherapy in metastatic HER2
      positive gastric cancers, resulted in improvements in response rates, time to
      progression and overall survival. Nevertheless, as with breast cancer, many
      patients with gastric cancer develop resistance to trastuzumab. Several promising
      therapies are currently being developed in combination with chemotherapy to
      increase the efficacy and overcome the cancer-resistance. Here we review the
      current overview of clinical application of agents targeting HER2 in gastric
      cancer. We also discuss the ongoing trials supporting the use of HER2-targeted
      agents combined with cytotoxic agents or other monoclonal antibodies. 

PMID- 25610850
TI  - Implant biomaterials: A comprehensive review.
AB  - Appropriate selection of the implant biomaterial is a key factor for long term
      success of implants. The biologic environment does not accept completely any
      material so to optimize biologic performance, implants should be selected to
      reduce the negative biologic response while maintaining adequate function. Every
      clinician should always gain a thorough knowledge about the different
      biomaterials used for the dental implants. This article makes an effort to
      summarize various dental bio-materials which were used in the past and as well as
      the latest material used now. 

PMID- 25610851
TI  - Vasopressors in obstetric anesthesia: A current perspective.
AB  - Vasopressors are routinely used to counteract hypotension after neuraxial
      anesthesia in Obstetrics. The understanding of the mechanism of hypotension and
      the choice of vasopressor has evolved over the years to a point where
      phenylephrine has become the preferred vasopressor. Due to the absence of
      definitive evidence showing absolute clinical benefit of one over the other,
      especially in emergency and high-risk Cesarean sections, our choice of
      phenylephrine over the other vasopressors like mephentermine, metaraminol, and
      ephedrine is guided by indirect evidence on fetal acid-base status. This review
      article evaluates the present day evidence on the various vasopressors used in
      obstetric anesthesia today. 

PMID- 25610853
TI  - Giant xanthogranuloma of the pelvis with S1 origin: Complete removal with only
      posterior approach, technical note.
AB  - Xanthogranulomas (XG) are benign proliferative disorder of histiocytes, a non
      Langerhans cell histiocytosis. Whose etiology is unknown. The nature of these
      lesions is controversial and could be either reactive or neoplastic; the presence
      of monoclonal cells does, however, favor the second hypothesis. Xanthogranuloma
      is frequently found in young adults and children (under 20 years old), mainly in
      the skin. In about 5%-10% of all Juvenile XG (JXG) cases xanthogranuloma are
      extracutaneous. Within this group, the site most frequently involved is the eye.
      Other involved organs are heart, liver, adrenals, oropharynx, lung, spleen,
      central nervous system and subcutaneous tissue, although involvement of the spine
      is uncommon. Isolated lesions involving the sacral region are extremely rare. To
      date, this is the first reported case of a giant JXG arising from S1 with
      extension into the pelvic region in an adult spine. 

PMID- 25610852
TI  - Posterior partially edentulous jaws, planning a rehabilitation with dental
      implants.
AB  - AIM: To discuss important characteristics of the use of dental implants in
      posterior quadrants and the rehabilitation planning. METHODS: An electronic
      search of English articles was conducted on MEDLINE (PubMed) from 1990 up to the
      period of March 2014. The key terms were dental implants and posterior jaws,
      dental implants/treatment planning and posterior maxilla, and dental
      implants/treatment planning and posterior mandible. No exclusion criteria were
      used for the initial search. Clinical trials, randomized and non randomized
      studies, classical and comparative studies, multicenter studies, in vitro and in
      vivo studies, case reports, longitudinal studies and reviews of the literature
      were included in this review. RESULTS: One hundred and fifty-two articles met the
      inclusion criteria of treatment planning of dental implants in posterior jaw and
      were read in their entirety. The selected articles were categorized with respect
      to their context on space for restoration, anatomic considerations (bone quantity
      and density), radiographic techniques, implant selection (number, position,
      diameter and surface), tilted and pterygoid implants, short implants, occlusal
      considerations, and success rates of implants placed in the posterior region. The
      results derived from the review process were described under several different
      topic headings to give readers a clear overview of the literature. In general, it
      was observed that the use of dental implants in posterior region requires a
      careful treatment plan. It is important that the practitioner has knowledge about
      the theme to evaluate the treatment parameters. CONCLUSION: The use of implants
      to restore the posterior arch presents many challenges and requires a detailed
      treatment planning.

PMID- 25610854
TI  - Conservative management of cervical pregnancy with intramuscular administration
      of methotrexate and KCl injection: Case report and review of the literature.
AB  - We report the case of a cervical pregnancy successfully treated with
      intramuscular injection of methotrexate (MTX) and intramniotic administration of
      potassium chloride. A 41-year-old woman was admitted to our Department with the
      suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty
      endometrial cavity, gestational sac within the cervical canal and embryonic echo
      measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine
      (beta-HCG) was measured 28590 IU/L. No cardiac activity was detected. The
      diagnosis of a cervical pregnancy was made. Patient was treated with
      intramuscular administration of methotrexate (50 mg/m(2)) in combination with
      ultrasound-guided intramniotic injection of KCl (2 meq/mL). Gradual decrease of
      beta-HCG levels as well as ultrasound observation of collapsed gestational sac
      was observed. No curettage was necessitated. Patient was discharged on day 10(th)
      and was set in follow-up on a weekly basis. beta-HCG values were measured < 10
      IU/L on 56(th) day after MTX administration. Intramuscular administration of MTX
      may be effective in treatment of cervical pregnancy without additional
      interventional measures. 

PMID- 25610855
TI  - Unusual disposition of lateral circumflex femoral artery: Anatomical description
      and clinical implications.
AB  - The anatomical knowledge of arterial variations of lower limb is of utmost
      significance for the present day surgeons and interventional radiologists for
      minimizing complications during vascular reconstructive procedures,
      catheterization procedures and surgical intervention for embolism. Lateral
      Circumflex Femoral Artery (LCFA) is an important branch of Profunda Femoris
      artery and precise knowledge of its variations can be of great relevance during
      surgical and radiological procedures in femoral region. The present study reports
      a unique case of anomalous route taken by LCFA posterior to femoral nerve
      associated with a prominent muscular branch from Femoral artery mimicking the
      course of LCFA. Documentation of such variations is highly significant. It may
      serve as guideline for surgeons in reducing the incidence of postoperative
      complications where LCFA is used as a long vascular pedicle in anterolateral
      perforator thigh flap and in breast reconstruction after mastectomy. Ignorance of
      such variations can lead to fatal intraoperative haemorrhage and incapacitating
      sensory and motor deficit due to injury to femoral nerve branches which are
      closely related to these vessels. 

PMID- 25610856
TI  - Endometriosis: novel models, diagnosis, and treatment.

PMID- 25610857
TI  - Latest treatment option and technology advancement in corneal and ocular surface
      disease.

PMID- 25610858
TI  - Phenomics research on coronary heart disease based on human phenotype ontology.
AB  - The characteristics of holistic, dynamics, complexity, and spatial and temporal
      features enable "Omics" and theories of TCM to interlink with each other. HPO,
      namely, "characterization," can be understood as a sorting and generalization of
      the manifestations shown by people with diseases on the basis of the phenomics.
      Syndrome is the overall "manifestation" of human body pathological and
      physiological changes expressed by four diagnostic methods' information. The four
      diagnostic methods' data could be the most objective and direct manifestations of
      human body under morbid conditions. In this aspect, it is consistent with the
      connation of "characterization." Meanwhile, the four diagnostic methods' data
      also equip us with features of characterization in HPO. In our study, we compared
      107 pieces of four diagnostic methods' information with the "characterization
      database" to further analyze data of four diagnostic methods' characterization in
      accordance with the common characteristics of four diagnostic methods'
      information and characterization and integrated 107 pieces of four diagnostic
      methods' data to relevant items in HPO and finished the expansion of
      characterization information in HPO. 

PMID- 25610859
TI  - Computational and bioinformatics techniques for immunology.

PMID- 25610860
TI  - ECM-like scaffolds: nature drives research.

PMID- 25610862
TI  - Molecular imaging: from bench to clinic.

PMID- 25610861
TI  - Experimental gestational diabetes mellitus induces blunted vasoconstriction and
      functional changes in the rat aorta.
AB  - Diabetic conditions increase vascular reactivity to angiotensin II in several
      studies but there are scarce reports on cardiovascular effects of hypercaloric
      diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this
      work was to determine the effects of HD induced GDM on vascular responses.
      Angiotensin II as well as phenylephrine induced vascular contraction was tested
      in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4
      before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD)
      diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and
      plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired
      vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in
      endothelium-free (e-) vessels. Losartan reduced GDM but not SD e-
      vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein
      expression were significantly increased in GDM vessels (P < 0.05 versus SD).
      Results suggest an increased participation of endothelium vasodilator mediators,
      probably prostaglandins, as well as of AT2 vasodilator receptors as a
      compensatory mechanism for vasoconstrictor changes generated by experimental GDM.
      Considering the short term of rat pregnancy findings can reflect early stage GDM
      adaptations. 

PMID- 25610863
TI  - Novel computing technologies for bioinformatics and cheminformatics.

PMID- 25610864
TI  - Inflammatory reaction in neurological diseases.

PMID- 25610866
TI  - Novel psychoactive substances and behavioral addictions.

PMID- 25610867
TI  - Therapeutic potential of natural pharmacological agents in the treatment of human
      diseases.

PMID- 25610865
TI  - DBC1/CCAR2 and CCAR1 Are Largely Disordered Proteins that Have Evolved from One
      Common Ancestor.
AB  - Deleted in breast cancer 1 (DBC1, CCAR2, KIAA1967) is a large, predominantly
      nuclear, multidomain protein that modulates gene expression by inhibiting several
      epigenetic modifiers, including the deacetylases SIRT1 and HDAC3, and the
      methyltransferase SUV39H1. DBC1 shares many highly conserved protein domains with
      its paralog cell cycle and apoptosis regulator 1 (CCAR1, CARP-1). In this study,
      we examined the full-length sequential and structural properties of DBC1 and
      CCAR1 from multiple species and correlated these properties with evolution. Our
      data shows that the conserved domains shared between DBC1 and CCAR1 have similar
      domain structures, as well as similar patterns of predicted disorder in less
      conserved intrinsically disordered regions. Our analysis indicates similarities
      between DBC1, CCAR1, and the nematode protein lateral signaling target 3 (LST-3),
      suggesting that DBC1 and CCAR1 may have evolved from LST-3. Our data also
      suggests that DBC1 emerged later in evolution than CCAR1. DBC1 contains regions
      that show less conservation across species as compared to the same regions in
      CCAR1, suggesting a continuously evolving scenario for DBC1. Overall, this study
      provides insight into the structure and evolution of DBC1 and CCAR1, which may
      impact future studies on the biological functions of these proteins. 

PMID- 25610868
TI  - Neural computation for rehabilitation.

PMID- 25610869
TI  - Otolaryngology, head and neck surgery.

PMID- 25610870
TI  - Lifestyle modification strategies to counteract the world epidemic growth of
      obesity and diabetes.

PMID- 25610871
TI  - Psychoeducation program on strategies for coping with stress in patients with
      temporomandibular joint dysfunction.
AB  - Lack of educational projects in the available literature was an inspiration to
      develop a psychoeducational program. The objective was to provide patients with
      basic information on the contribution of stressors in the occurrence of
      temporomandibular joint dysfunction and educate on methods for coping with stress
      most commonly used in psychology. In the course of three meetings, patients are
      familiarised with the issue of experienced stress as a potential source of
      psychosomatic illnesses (in particular, temporomandibular joint dysfunction).
      Preliminary patients' opinions, expressed through self-report methods, indicate
      significant usefulness of the developed psychoeducational program for the process
      of treatment and the quality of patients' lives. 

PMID- 25610873
TI  - Cardiac arrest and cardiopulmonary resuscitation: starting from basic science and
      bioengineering research to improve resuscitation outcome.

PMID- 25610872
TI  - Prostaglandin E2 labour induction with intravaginal (Minprostin) versus
      intracervical (Prepidil) administration at term: randomized study of maternal and
      neonatal outcome and patient's perception using the osgood semantic differential
      scales.
AB  - AIM: To compare the efficacy, safety, and patient's perception of two
      prostaglandin E2 application methods for induction of labour. METHOD: Above 36th
      weeks of gestation, all women, who were admitted to hospital for induction of
      labour, were prospectively randomised to intravaginal 1 mg or intracervical 0.5
      mg irrespective of cervical Bishop score. The main outcome variables were
      induction-to-delivery interval, number of foetal blood samples, PDA rate, rate of
      oxytocin augmentation, rate of vaginal delivery, and patient's perception using
      semantic differential questionnaire. RESULTS: Thirty-nine patients were enrolled
      in this study. There was no statistical significant difference between the two
      groups in regard to perceptions of induction. The median induction delivery time
      using intravaginal versus intracervical administration was 29.9 versus 12.8
      hours, respectively (P = 0.04). No statistically difference between the groups
      was detected in regard to parity, gestation age, cervical Bishop score, number of
      foetal blood samples, PDA rate, rate of oxytocin augmentation, and mode of birth.
      SUMMARY: Irrespective of the cervical Bishop Score, intracervical gel had a
      shorter induction delivery time without impingement on the women's perception of
      induction.

PMID- 25610874
TI  - Novel bioinformatics approaches for analysis of high-throughput biological data.

PMID- 25610875
TI  - Peptic ulcer diseases: genetics, mechanism, and therapies.

PMID- 25610876
TI  - Plasma cell neoplasms: genetics, pathobiology, and new therapeutic strategies.

PMID- 25610877
TI  - The class I histone deacetylase inhibitor MS-275 prevents pancreatic beta cell
      death induced by palmitate.
AB  - Elevation of the dietary saturated fatty acid palmitate contributes to the
      reduction of functional beta cell mass in the pathogenesis of type 2 diabetes.
      The diabetogenic effect of palmitate is achieved by increasing beta cell death
      through induction of the endoplasmic reticulum (ER) stress markers including
      activating transcription factor 3 (Atf3) and CAAT/enhancer-binding protein
      homologous protein-10 (Chop). In this study, we investigated whether treatment of
      beta cells with the MS-275, a HDAC1 and HDAC3 activity inhibitor which prevents
      beta cell death elicited by cytokines, is beneficial for combating beta cell
      dysfunction caused by palmitate. We show that culture of isolated human islets
      and MIN6 cells with MS-275 reduced apoptosis evoked by palmitate. The protective
      effect of MS-275 was associated with the attenuation of the expression of Atf3
      and Chop. Silencing of HDAC3, but not of HDAC1, mimicked the effects of MS-275 on
      the expression of the two ER stress markers and apoptosis. These data point to
      HDAC3 as a potential drug target for preserving beta cells against lipotoxicity
      in diabetes.

PMID- 25610878
TI  - Hyperglycemia inhibits complement-mediated immunological control of S. aureus in
      a rat model of peritonitis.
AB  - Hyperglycemia from diabetes is associated with increased risk of infection from
      S. aureus and increased severity of illness. Previous work in our laboratory
      demonstrated that elevated glucose (>6 mM) dramatically inhibited S. aureus
      initiated complement-mediated immune effectors. Here we report in vivo studies
      evaluating the extent to which a hyperglycemic environment alters complement
      mediated control of S. aureus infection in a rat peritonitis model. Rats were
      treated with streptozocin to induce diabetes or sham-treated and then inoculated
      i.p. with S. aureus. Rats were euthanized and had peritoneal lavage at 2 or 24
      hours after infection to evaluate early and late complement-mediated effects.
      Hyperglycemia decreased the influx of IgG and complement components into the
      peritoneum in response to S. aureus infection and decreased anaphylatoxin
      generation. Hyperglycemia decreased C4-fragment and C3-fragment opsonization of
      S. aureus recovered in peritoneal fluids, compared with euglycemic or insulin
      rescued rats. Hyperglycemic rats showed decreased phagocytosis efficiency
      compared with euglycemic rats, which correlated inversely with bacterial
      survival. These results suggest that hyperglycemia inhibited humoral effector
      recruitment, anaphylatoxin generation, and complement-mediated opsonization of S.
      aureus, suggesting that hyperglycemic inhibition of complement effectors may
      contribute to the increased risk and severity of S. aureus infections in diabetic
      patients.

PMID- 25610881
TI  - CLIPPERS: Induction and maintenance of remission using hydroxychloroquine.

PMID- 25610879
TI  - Hyperglycemia induces Toll-like receptor-2 and -4 expression and activity in
      human microvascular retinal endothelial cells: implications for diabetic
      retinopathy.
AB  - Diabetic retinopathy (DR) causes visual impairment in working age adults and
      hyperglycemia-mediated inflammation is central in DR. Toll-like receptors (TLRs)
      play a key role in innate immune responses and inflammation. However, scanty data
      is available on their role in DR. Hence, in this study, we examined TLR2 and TLR4
      mRNA and protein expression and activity in hyperglycemic human retinal
      endothelial cells (HMVRECs). HMVRECs were treated with hyperglycemia (HG) or
      euglycemia and mRNA and protein levels of TLR-2, TLR-4, MyD88, IRF3, and TRIF as
      well as NF-kappaB p65 activation were measured. IL-8, IL-1beta, TNF-alpha and MCP
      1, ICAM-1, and VCAM-1 as well as monocyte adhesion to HMVRECs were also assayed.
      HG (25 mM) significantly induced TLR2 and TLR4 mRNA and protein in HMVRECs. It
      also increased both MyD88 and non-MyD88 pathways, nuclear factor-kappaB (NF
      kappaB), biomediators, and monocyte adhesion. This inflammation was attenuated by
      TLR-4 or TLR-2 inhibition, and dual inhibition by a TLR inhibitory peptide as
      well as TLR2 and 4 siRNA. Additionally, antioxidant treatment reduced TLR-2 and
      TLR4 expression and downstream inflammatory markers. Collectively, our novel data
      suggest that hyperglycemia induces TLR-2 and TLR-4 activation and downstream
      signaling mediating increased inflammation possibly via reactive oxygen species
      (ROS) and could contribute to DR.

PMID- 25610880
TI  - Sodium meta-arsenite ameliorates hyperglycemia in obese diabetic db/db mice by
      inhibition of hepatic gluconeogenesis.
AB  - Sodium meta-arsenite (SA) is implicated in the regulation of hepatic
      gluconeogenesis-related genes in vitro; however, the effects in vivo have not
      been studied. We investigated whether SA has antidiabetic effects in a type 2
      diabetic mouse model. Diabetic db/db mice were orally intubated with SA (10 mg
      kg(-1) body weight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood
      glucose levels, food intake, and body weight. We performed glucose, insulin, and
      pyruvate tolerance tests and analyzed glucose production and the expression of
      gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using
      a comprehensive animal metabolic monitoring system. SA-treated diabetic db/db
      mice had reduced concentrations of HbA1c and blood glucose levels. Exogenous
      glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of
      genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and
      phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver
      of SA-treated diabetic db/db mice. In primary hepatocytes, SA treatment decreased
      glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear
      factor 4 alpha (HNF-4alpha) mRNA. Small heterodimer partner (SHP) mRNA expression
      was increased in hepatocytes dependent upon the SA concentration. The expression
      of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1
      (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated
      diabetic db/db mice showed reduced energy expenditure. Oral intubation of SA
      ameliorates hyperglycemia in db/db mice by reducing hepatic gluconeogenesis
      through the decrease of Sirt1 expression and increase in acetylated FoxO1.

PMID- 25610882
TI  - Markers of JC virus infection in patients with multiple sclerosis under
      natalizumab therapy.
AB  - OBJECTIVE: To evaluate the frequency of JC polyomavirus (JCPyV) infection and
      anti-JCPyV antibodies in patients with multiple sclerosis under natalizumab
      therapy. METHODS: Presence of anti-JCPyV antibodies and JCPyV DNA was analyzed in
      39 patients with relapsing-remitting multiple sclerosis undergoing natalizumab
      therapy. Anti-JCPyV antibodies were evaluated in serum by a 2-step virus-like
      particle-based ELISA assay (Stratify), and JCPyV DNA was evaluated in peripheral
      blood mononuclear cells, plasma, and urine by quantitative PCR. The anti-JCPyV
      antibodies were evaluated in serum samples collected at the same time or later
      than those collected for DNA analysis. RESULTS: JCPyV DNA was detected in 59% of
      patients, and anti-JCPyV antibodies were present in 67%. JCPyV DNA occurred more
      often in blood than in urine. Anti-JCPyV antibodies were observed in 70% of the
      JCPyV-infected patients, and JCPyV DNA was detected in 50% of the patients
      without anti-JCPyV antibodies. When JCPyV DNA was investigated in blood and urine
      the frequency of infection was higher than previously described. CONCLUSION:
      Under these experimental conditions, with respect to the observed frequency of
      JCPyV infection, the sensitivity of the anti-JCPyV antibody assay was lower than
      expected.

PMID- 25610883
TI  - Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with
      hepatitis C.
AB  - OBJECTIVE: This study examined neurologic abnormalities (as measured by proton
      magnetic resonance spectroscopy imaging and diffusion tensor imaging),
      neurocognitive performance, and fatigue among a sample of adults with hepatitis C
      virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural
      brain abnormalities and neurocognitive compromise consistent with frontostriatal
      dysfunction as well as increased fatigue compared to controls. METHOD:
      Participants were 76 individuals diagnosed with HCV and 20 controls who underwent
      a comprehensive neurocognitive evaluation and clinical assessments. A subset of
      the HCV+ participants (n = 29) and all controls underwent MRI. RESULTS:
      Individuals diagnosed with chronic HCV infection demonstrated greater fractional
      anisotropy in the striatum as well as greater mean diffusivity in the fronto
      occiptal fasciculus and external capsule compared to HCV- controls. HCV+
      participants also demonstrated lower levels of N-acetylaspartate in bilateral
      parietal white matter and elevations in myo-inosital (mI) in bilateral frontal
      white matter compared to HCV- controls (all p values < 0.05). HCV+ participants
      also demonstrated significantly poorer neuropsychological performance,
      particularly in processing speed and verbal fluency. HCV+ patients reported
      higher levels of fatigue than controls, and fatigue was significantly correlated
      with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in
      frontal white matter, and overall cognitive performance. CONCLUSIONS: Our results
      suggest that HCV-associated neurologic complications disrupt frontostriatal
      structures, which may result in increased fatigue and poorer cognitive
      performance, particularly in those cognitive domains regulated by frontostriatal
      regions.

PMID- 25610884
TI  - Renal dysfunction in fetal alcohol syndrome: a potential contributor on
      developmental disabilities of offspring.

PMID- 25610885
TI  - Parasites and chronic renal failure.
AB  - Suppression of the human immune system results in an increase in susceptibility
      to infection by various infectious agents. Conditions such as AIDS, organ
      transplantation and chronic renal insufficiency (CRI) are the most important
      cause of insufficient immune response against infections. Long term renal
      disorders result in uremia, which can suppress human immune system. Parasitic
      infections are one of the most important factors indicating the public health
      problems of the societies. These infections can be more hostile and life
      threatening in susceptible individuals than in the normal people. In these
      patients some parasitic infections such as blastocystiosis, cryptosporidiosis and
      toxoplasmosis have been reported to be more prevalent. This review aimed to give
      an overview about parasitic infections in patients with renal disorders. 

PMID- 25610886
TI  - Whole slide images for primary diagnostics of urinary system pathology: a
      feasibility study.
AB  - INTRODUCTION: During the last decade, whole slide images (WSI) have been used in
      many areas of pathology such as teaching, research, digital archiving,
      teleconsultation and quality assurance testing. However, WSI have as yet not much
      been used for upfront diagnostics because of the lack of validation studies.
      OBJECTIVES: The aim of this study was to test the feasibility of WSI for primary
      diagnosis of urinary tract pathology. MATERIALS AND METHODS: 100 consecutive
      urinary tract biopsies and resections which had been diagnosed conventionally
      between the years 2008-2009 were scanned at 20* magnification, and rediagnosed by
      two pathologists on WSI, having the original clinical information available, but
      blinded to the original diagnoses. Original and WSI diagnoses were compared and
      classified as concordant, slightly discordant (without clinical consequences) and
      discordant. RESULTS: Original and WSI based rediagnosis were concordant in 87% of
      the cases. Original and WSI diagnosis were slightly discordant in 8% of cases.
      Major discrepancies with clinical or prognostic implications were founded in only
      5 cases. However, for 6 out of the 13 discrepancies, WSI based diagnoses were
      considered to be better than the original diagnoses. CONCLUSION: Primary
      diagnostics of urinary tract specimens can be reliably done on WSI. Further
      improvements of image resolution may help to increase diagnostic accuracy and WSI
      acceptance in routine pathology.

PMID- 25610887
TI  - The frequency of candiduria in hospitalized patients with depressive syndrome.

PMID- 25610888
TI  - Consequences of hypomagnesemia in type 2 diabetes mellitus patients.

PMID- 25610889
TI  - Association of helicobacter pylori infection with serum magnesium in kidney
      transplant patients.
AB  - INTRODUCTION: Few studies are available regarding the various promoting factors
      of H. pylori infection in kidney disease patients especially renal transplant
      individuals. OBJECTIVES: This study was therefore conducted to examine the
      association of serum magnesium with H. pylori infection among kidney transplant
      patients. This cross-sectional investigation was conducted on a group of stable
      kidney transplant patients. Peripheral venous blood samples were collected for
      biochemical analysis after an overnight fast, Also urea breath test (UBT) was
      conducted for patients. PATIENTS AND METHODS: A total of 50 cases was enrolled to
      the study. Mean serum magnesium value of the patients was 1.98 +/- 0.62 mg/dl.
      Serum magnesium level in positive H. pylori patients was more than negative H.
      pylori patients (p=0.0005). In this study population, there was no significant
      difference in serum intact PTH, calcium, alkaline phosphatase, albumin levels and
      body mass index (BMI) between males and females or H. pylori positive and H.
      pylori negative subjects (p>0.5). CONCLUSION: It is possible that, magnesium
      aggravates H. pylori infection in kidney transplant patients through the
      mechanisms like hemodialysis, which we had reported previously. However, more
      studies are necessary to prove the association of magnesium with H. pylori
      infection in renal transplant patients and finding the clinical relevance of our
      findings.

PMID- 25610890
TI  - Glomerulocystic kidney presenting as an incidental finding in an adult male with
      unilateral non-functioning kidney.

PMID- 25610891
TI  - The role of diabetes mellitus and hypertension in chronic kidney disease.

PMID- 25610893
TI  - Spatial distribution and temporal variability of ammonium-nitrogen, phosphorus,
      and potassium in a rice field in Corrientes, Argentina.
AB  - Proper and effective management of soil nutrients requires assessment of their
      variability at the field scale. We compare the effects of lime amendment rate on
      the spatial variability of three macronutrient forms (NH4 (+)-N, Olsen P, and
      Mehlich-1 K) in a paddy soil at three different dates during the growth period of
      a rice crop. The field work was carried out near Corrientes, Argentina. Lime
      treatments were 0, 625, and 1250 kg ha(-1) dolomite, and each liming dose was
      applied to a 1.7 ha field. Ninety-three soil samples per treatment were first
      collected in aerobic conditions and then two more times after flooding, at bunch
      formation and flowering. Soil NH4 (+)-N increased along time, whereas P was
      highest at bunch formation and K steadily decreased along the rice growth period.
      Dolomite addition increased macronutrient availability at the first and second
      samplings, but its effects at the third sampling depended on the element. The
      three soil nutrients analyzed displayed strong patterns of spatial dependence for
      the three lime treatments and at the three periods studied. The areas with
      relative high or low macronutrient concentrations within each field were not
      stable throughout the rice growth period. Seasonality in the spatial distribution
      of macronutrients may be of agronomic value for site specific management.

PMID- 25610892
TI  - Biochemical and physiological studies on the effects of senescence leaves of
      Populus deltoides on Triticum vulgare.
AB  - Triticum vulgare (Wheat) based products are the major dietary source of food in
      developing countries. In India, it grows in association with boundary plantations
      of Populus deltoids (poplar). During winter, poplar enters in dormancy which
      cause a heavy leaf fall at the time of wheat seed germination. Large number of
      poplar senescence leaves may adversely affect the wheat. Therefore, the present
      study was performed to examine the effect of senescence poplar leaves on wheat
      germ and some other biochemical parameters. Seed's germination rate was
      determined by measuring root and shoot lengths, percent germination, germination
      index, and inhibition percentage. Biochemical parameters, namely, pigment,
      carbohydrate, protein, and phenol content, were estimated. Activities of catalase
      and polyphenol oxidase which are stress marker enzymes were also measured.
      Results revealed that germination and other biochemical parameters of wheat were
      severely affected by senescence poplar leaves even at very low concentration. So,
      intercropping of poplar along with wheat may be chosen carefully as wheat is the
      major dietary staple. 

PMID- 25610894
TI  - Clinical and radiological results over the medium term of isolated acetabular
      revision.
AB  - Acetabular cup loosening is associated with pain, reduced function, and
      instability of the implant. If such event happens while the femoral implant is in
      a satisfactory position and is well fixed to the bone, isolated acetabular
      revision surgery is indicated. The aim of this single-center retrospective study
      was to evaluate the clinical and radiological results over the medium term (12
      month follow-up mean 36, max 60) of isolated acetabular revisions surgery using a
      porous hemispheric revision shell matched with a cemented all-poly cup and large
      diameter femoral head (>32). 33 patients were enrolled. We collect any relevant
      data from the clinical board. Routine clinical and radiographic examinations were
      performed preoperatively; the postoperative follow-up was made at 1, 3, and 6
      months and yearly thereafter. At the last available follow-up, we report
      satisfactory improvement of functional scores in all the patients; 2 patients
      (6.1%) showed thigh pain and only 4 hips (12.11%) presented mild groin pain; all
      the femoral components are well fixed and there were no potential or pending
      rerevisions. With bias due to the follow-up and to the retrospective design of
      the study, we report clinical, functional, and radiological satisfactory results.

PMID- 25610895
TI  - Plant abio-stress and bioresources utilization for sustainable development.

PMID- 25610896
TI  - Effects of salinity, temperature, and polyethylene glycol on the seed germination
      of sunflower (Helianthus annuus L.).
AB  - Salinization has severe influences on agriculture in the whole world. The main
      aims of this work were to evaluate osmotic effect and ion effect of NaCl on seed
      germination of three sunflower (Helianthus annuus L.) cultivars interacting with
      three alternating temperature regimes and to select the most salt tolerant
      cultivars to plant in the saline region. Seeds were germinated in the isotonic
      NaCl and polyethylene glycol (PEG) solutions of -0.45, -0.90, -1.34, -1.79, and 
      2.24 MPa at 10:20, 15:25, and 20:30  degrees C temperature regimes. Both NaCl and
      PEG inhibited germination, but the effects of NaCl were less as compared to that
      of PEG, which means that adverse effects of PEG on germination were due to
      osmotic effect rather than specific ion accumulation. For the three cultivars,
      higher germination occurred at 10:20  degrees C in NaCl treatments and at 20:30 
      degrees C in the isotonic PEG treatments. Among the three cultivars, Sandaomei
      (SDM) is the most tolerant to salt and PEG stress.

PMID- 25610897
TI  - A modular neural network scheme applied to fault diagnosis in electric power
      systems.
AB  - This work proposes a new method for fault diagnosis in electric power systems
      based on neural modules. With this method the diagnosis is performed by assigning
      a neural module for each type of component comprising the electric power system,
      whether it is a transmission line, bus or transformer. The neural modules for
      buses and transformers comprise two diagnostic levels which take into
      consideration the logic states of switches and relays, both internal and back-up,
      with the exception of the neural module for transmission lines which also has a
      third diagnostic level which takes into account the oscillograms of fault
      voltages and currents as well as the frequency spectrums of these oscillograms,
      in order to verify if the transmission line had in fact been subjected to a
      fault. One important advantage of the diagnostic system proposed is that its
      implementation does not require the use of a network configurator for the system;
      it does not depend on the size of the power network nor does it require
      retraining of the neural modules if the power network increases in size, making
      its application possible to only one component, a specific area, or the whole
      context of the power system. 

PMID- 25610898
TI  - Evaluation of halogenated coumarins for antimosquito properties.
AB  - Mosquitoes are the major vectors of parasites and pathogens affecting humans and
      domestic animals. The widespread development of insecticide resistance and
      negative environmental effects of most synthetic compounds support an interest in
      finding and developing alternative products against mosquitoes. Natural coumarins
      and synthetic coumarin analogues are known for their several pharmacological
      properties, including being insecticidal. In the present study halogenated
      coumarins (3-mono/dibromo acetyl, 6-halogenated coumarin analogues) were screened
      for larvicidal, adulticidal, and repellent properties against Anopheles
      arabiensis, a zoophilic mosquito that is one of the dominant vectors of malaria
      in Africa. Five compounds exerted 100% larval mortality within 24 h of exposure.
      All coumarins and halogenated coumarins reversibly knocked down adult mosquitoes
      but did not kill them after 24 h of exposure. Repellent properties could not be
      evidenced. Five compounds were considered potential larvicidal agents for further
      research and development, while adulticidal activity was considered only mild to
      moderate.

PMID- 25610899
TI  - Using soil apparent electrical conductivity to optimize sampling of soil
      penetration resistance and to improve the estimations of spatial patterns of soil
      compaction.
AB  - This study presents a combined application of an EM38DD for assessing soil
      apparent electrical conductivity (ECa) and a dual-sensor vertical penetrometer
      Veris-3000 for measuring soil electrical conductivity (ECveris) and soil
      resistance to penetration (PR). The measurements were made at a 6 ha field
      cropped with forage maize under no-tillage after sowing and located in
      Northwestern Spain. The objective was to use data from ECa for improving the
      estimation of soil PR. First, data of ECa were used to determine the optimized
      sampling scheme of the soil PR in 40 points. Then, correlation analysis showed a
      significant negative relationship between soil PR and ECa, ranging from -0.36 to 
      0.70 for the studied soil layers. The spatial dependence of soil PR was best
      described by spherical models in most soil layers. However, below 0.50 m the
      spatial pattern of soil PR showed pure nugget effect, which could be due to the
      limited number of PR data used in these layers as the values of this parameter
      often were above the range measured by our equipment (5.5 MPa). The use of ECa as
      secondary variable slightly improved the estimation of PR by universal cokriging,
      when compared with kriging.

PMID- 25610900
TI  - Chemical attributes of soil fertilized with cassava mill wastewater and
      cultivated with sunflower.
AB  - The use of waste arising from agroindustrial activities, such as cassava
      wastewater, has been steadily implemented in order to reduce environmental
      pollution and nutrient utilization. The aim of this study is that the changes in
      chemical properties of dystrophic red-yellow latosol (oxisol) were evaluated at
      different sampling times after reuse of cassava wastewater as an alternative to
      mineral fertilizer in the cultivation of sunflower, hybrid Helio 250. The
      experiment was conducted at the Experimental Station of the Agricultural Research
      Company of Pernambuco (IPA), located in Vitoria de Santo Antao. The experimental
      design was randomized blocks with 6 * 5 subplots; six doses of cassava wastewater
      (0; 8.5; 17.0; 34.0; 68.0; and 136 m(3) ha(-1)); and five sampling times (21, 42,
      63, 84, and 105 days after applying the cassava wastewater), with four
      replications. Concentrations of available phosphorus and exchangeable potassium,
      calcium, magnesium and sodium, pH, and electrical conductivity of the soil
      saturation extract were evaluated. Results indicate that cassava wastewater is an
      efficient provider of nutrients to the soil and thus to the plants, making it an
      alternative to mineral fertilizers.

PMID- 25610901
TI  - Optimization of aeration and agitation rate for lipid and gamma linolenic acid
      production by Cunninghamella bainieri 2A1 in submerged fermentation using
      response surface methodology.
AB  - The locally isolated filamentous fungus Cunninghamella bainieri 2A1 was
      cultivated in a 5 L bioreactor to produce lipid and gamma-linolenic acid (GLA).
      The optimization was carried out using response surface methodology based on a
      central composite design. A statistical model, second-order polynomial model, was
      adjusted to the experimental data to evaluate the effect of key operating
      variables, including aeration rate and agitation speed on lipid production.
      Process analysis showed that linear and quadratic effect of agitation intensity
      significantly influenced lipid production process (P < 0.01). The quadratic model
      also indicated that the interaction between aeration rate and agitation speed had
      a highly significant effect on lipid production (P < 0.01). Experimental results
      showed that a lipid content of 38.71% was produced in optimum conditions using an
      airflow rate and agitation speed of 0.32 vvm and 599 rpm, respectively. Similar
      results revealed that 0.058(g/g) gamma-linolenic acid was produced in optimum
      conditions where 1.0 vvm aeration rate and 441.45 rpm agitation rate were used.
      The regression model confirmed that aeration and agitation were of prime
      importance for optimum production of lipid in the bioreactor.

PMID- 25610902
TI  - Investigation of CPD and HMDS sample preparation techniques for cervical cells in
      developing computer-aided screening system based on FE-SEM/EDX.
AB  - This paper investigated the effects of critical-point drying (CPD) and
      hexamethyldisilazane (HMDS) sample preparation techniques for cervical cells on
      field emission scanning electron microscopy and energy dispersive X-ray (FE
      SEM/EDX). We investigated the visualization of cervical cell image and elemental
      distribution on the cervical cell for two techniques of sample preparation. Using
      FE-SEM/EDX, the cervical cell images are captured and the cell element
      compositions are extracted for both sample preparation techniques. Cervical cell
      image quality, elemental composition, and processing time are considered for
      comparison of performances. Qualitatively, FE-SEM image based on HMDS preparation
      technique has better image quality than CPD technique in terms of degree of
      spread cell on the specimen and morphologic signs of cell deteriorations (i.e.,
      existence of plate and pellet drying artifacts and membrane blebs).
      Quantitatively, with mapping and line scanning EDX analysis, carbon and oxygen
      element compositions in HMDS technique were higher than the CPD technique in
      terms of weight percentages. The HMDS technique has shorter processing time than
      the CPD technique. The results indicate that FE-SEM imaging, elemental
      composition, and processing time for sample preparation with the HMDS technique
      were better than CPD technique for cervical cell preparation technique for
      developing computer-aided screening system. 

PMID- 25610903
TI  - Preventing HIV transmission in Chinese internal migrants: a behavioral approach.
AB  - This study is a step towards a behavioral intervention to prevent HIV
      transmission among Chinese internal migrants. To explore important and changeable
      determinants of condom use and inspect effective and feasible methods to increase
      condom use for the target population, we conducted a three-round web-based Delphi
      study among a panel of 62 experts between October 2012 and March 2013. The
      panelists were purposely selected using a stepwise procedure to represent topic
      related areas of expertise. The response rate per round ranges from 21% to 81%.
      The panelists identified 19 possible determinants of condom use and reported 16
      intervention methods they considered successful. They agreed that attitude
      towards condom use was the most important and changeable determinant, while
      applying behavioral theory, increasing sexual education and condom access,
      performing worksite health promotion, detecting risk factors, and working closely
      with relevant organizations and the government were effective and feasible
      methods to increase condom use among internal migrants in China. In conclusion,
      results of this study highlight the importance of attitude in changing condom use
      and underscore the need to apply behavior theory and integrate multiple
      educational approaches for developing behavioral HIV prevention interventions
      targeting internal migrants in China. 

PMID- 25610904
TI  - Computational intelligence and metaheuristic algorithms with applications.

PMID- 25610905
TI  - Effect of aerobics exercise on self-esteem in Iranian female adolescents covered
      by welfare organization.
AB  - INTRODUCTION: Deprivation of parents might decrease self-esteem (SE) and result
      in affective and social incompatibility. In this randomized control trial, we
      examined the effect of aerobics exercise on SE among female adolescents living
      with no natural family. MATERIALS AND METHODS: The sample consisted of all female
      adolescents aged 13 to 19 years (n: 72) who were covered by Isfahan Welfare
      organization. Participants were assigned into intervention and control groups by
      matched random sampling. Intervention included 8 weeks of aerobics exercise.
      Coppersmith SE inventory was administered before and after intervention as well
      as after one month follow-up. RESULTS: No significant difference was seen between
      pre-SE scores of intervention (32.7 +/- 8.4) and control (33.0 +/- 6.7) groups (t
      = .16, P = .87). A significant difference was obtained in post-SE scores (40.2 +/
      5.7 versus 34.7 +/- 6.8, t = 3.58, P = .001) and in one month follow-up scores
      (36.4 +/- 5.2 versus 33.0 +/- 5.2, t = 2.25, P = .03). DISCUSSION: The results
      demonstrated a low level of pre-SE in both groups. However, a significant
      improvement was seen in posttest of intervention group which persisted even one
      month after intervention. It supports the use of aerobics for female adolescents
      deprived from family life.

PMID- 25610906
TI  - #Nitrosocarbonyls 1: antiviral activity of N-(4-hydroxycyclohex-2-en-1
      yl)quinoline-2-carboxamide against the influenza A virus H1N1.
AB  - Influenza virus flu A H1N1 still remains a target for its inhibition with small
      molecules. Fleeting nitrosocarbonyl intermediates are at work in a short-cut
      synthesis of carbocyclic nucleoside analogues. The strategy of the synthetic
      approaches is presented along with the in vitro antiviral tests. The nucleoside
      derivatives were tested for their inhibitory activity against a variety of
      viruses. Promising antiviral activities were found for specific compounds in the
      case of flu A H1N1. 

PMID- 25610907
TI  - Effects of land use change and seasonality of precipitation on soil nitrogen in a
      dry tropical forest area in the Western Llanos of Venezuela.
AB  - We evaluated changes of different soil nitrogen forms (total N, available
      ammonium and nitrate, total N in microbial biomass, and soil N mineralization)
      after conversion of semideciduous dry tropical forest in 5- and 18-year-old
      pastures (YP and OP, resp.) in the western Llanos of Venezuela. This evaluation
      was made at early rainy season, at end rainy season, and during dry season. With
      few exceptions, no significant differences were detected in the total N in the
      three study sites. Compared to forest soils, YP showed ammonium losses from 4.2
      to 62.9% and nitrate losses from 20.0 to 77.8%, depending on the season of the
      year. In OP, the ammonium content increased from 50.0 to 69.0% at the end of the
      rainy season and decreased during the dry season between 25.0 and 55.5%, whereas
      the nitrate content increased significantly at early rainy season. The net
      mineralization and the potentially mineralizable N were significantly higher (P <
      0.05) in OP than in forest and YP, which would indicate a better quality of the
      substrate in OP for mineralization. The mineralization rate constant was higher
      in YP than in forest and OP. This could be associated with a reduced capacity of
      these soils to preserve the available nitrogen. 

PMID- 25610909
TI  - Recent advances in information security.

PMID- 25610908
TI  - County-scale spatial distribution of soil enzyme activities and enzyme activity
      indices in agricultural land: implications for soil quality assessment.
AB  - Here the spatial distribution of soil enzymatic properties in agricultural land
      was evaluated on a county-wide (567 km(2)) scale in Changwu, Shaanxi Province,
      China. The spatial variations in activities of five hydrolytic enzymes were
      examined using geostatistical methods. The relationships between soil enzyme
      activities and other soil properties were evaluated using both an integrated
      total enzyme activity index (TEI) and the geometric mean of enzyme activities
      (GME). At the county scale, soil invertase, phosphatase, and catalase activities
      were moderately spatially correlated, whereas urease and dehydrogenase activities
      were weakly spatially correlated. Correlation analysis showed that both TEI and
      GME were better correlated with selected soil physicochemical properties than
      single enzyme activities. Multivariate regression analysis showed that soil OM
      content had the strongest positive effect while soil pH had a negative effect on
      the two enzyme activity indices. In addition, total phosphorous content had a
      positive effect on TEI and GME in orchard soils, whereas alkali-hydrolyzable
      nitrogen and available potassium contents, respectively, had negative and
      positive effects on these two enzyme indices in cropland soils. The results
      indicate that land use changes strongly affect soil enzyme activities in
      agricultural land, where TEI provides a sensitive biological indicator for soil
      quality.

PMID- 25610910
TI  - Proposed framework for the evaluation of standalone corpora processing systems:
      an application to Arabic corpora.
AB  - Despite the accessibility of numerous online corpora, students and researchers
      engaged in the fields of Natural Language Processing (NLP), corpus linguistics,
      and language learning and teaching may encounter situations in which they need to
      develop their own corpora. Several commercial and free standalone corpora
      processing systems are available to process such corpora. In this study, we first
      propose a framework for the evaluation of standalone corpora processing systems
      and then use it to evaluate seven freely available systems. The proposed
      framework considers the usability, functionality, and performance of the
      evaluated systems while taking into consideration their suitability for Arabic
      corpora. While the results show that most of the evaluated systems exhibited
      comparable usability scores, the scores for functionality and performance were
      substantially different with respect to support for the Arabic language and N
      grams profile generation. The results of our evaluation will help potential users
      of the evaluated systems to choose the system that best meets their needs. More
      importantly, the results will help the developers of the evaluated systems to
      enhance their systems and developers of new corpora processing systems by
      providing them with a reference framework. 

PMID- 25610911
TI  - Efficient bounding schemes for the two-center hybrid flow shop scheduling problem
      with removal times.
AB  - We focus on the two-center hybrid flow shop scheduling problem with identical
      parallel machines and removal times. The job removal time is the required
      duration to remove it from a machine after its processing. The objective is to
      minimize the maximum completion time (makespan). A heuristic and a lower bound
      are proposed for this NP-Hard problem. These procedures are based on the optimal
      solution of the parallel machine scheduling problem with release dates and
      delivery times. The heuristic is composed of two phases. The first one is a
      constructive phase in which an initial feasible solution is provided, while the
      second phase is an improvement one. Intensive computational experiments have been
      conducted to confirm the good performance of the proposed procedures. 

PMID- 25610912
TI  - Effect of nitrogen source and inorganic phosphate concentration on methanol
      utilization and PEX genes expression in Pichia pastoris.
AB  - Methylotrophic yeast Pichia pastoris has proved to be especially useful for
      production of various heterologous proteins. In biotechnology it is very
      important to maintain the balance between high levels of heterologous gene
      expression and cell viability. Decisive understanding of gene regulation
      mechanisms is essential for reaching this goal. In this study, we investigated
      the effect of different nitrogen sources and phosphate concentration in media on
      methanol utilization. It was shown that expression levels of main genes, which
      are involved in methanol utilization (MUT genes) and in functioning of
      peroxisomes (PEX genes), are maximal when ammonium sulphate is used as a nitrogen
      source. Expression of these genes is decreased in media with poor nitrogen
      sources, such as proline. Addition of rapamycin to the media completely removed
      repression of AOX1 promoter in media with proline, which allows proposing that
      Tor-kinase is involved in establishing of nitrogen regulation of this gene. It
      was also shown that MUT genes expression levels get higher, when the phosphate
      concentration in media is increased. 

PMID- 25610913
TI  - A retrospective review of outcomes of dental treatment performed for special
      needs patients under general anaesthesia: 2-year follow-up.
AB  - OBJECTIVE: The purpose of the study was to evaluate the follow-up pattern of
      special needs patients (SNP) treated under general anaesthesia (GA) and the
      failure rates of different treatment procedures and restorative materials. STUDY
      DESIGN: The treatment records of the patients who received dental treatment under
      GA during 2005 to 2009 were reviewed. The duration of follow-up periods, the
      outcomes of different treatment procedures, and the quality of different
      restorative materials were recorded and evaluated. Statistics were used for the
      comparison (SPSS 20.0). Pearson's chi-square test and post hoc analysis were used
      to evaluate the attendance of postoperative appointments and the associations of
      failure rates of different treatment procedures and restorative materials. Cohen
      kappa statistics was used for intraexaminer reliability. RESULTS: A total of 177
      patients were included in the study. The attendance of postoperative appointments
      showed a gradual decrease from 96% to 36% within 24 months (P < 0.05).
      Restorative procedures had the highest failure rates among all treatment
      procedures (P < 0.05). Stainless steel crowns showed higher survival rates among
      different restorative materials (P < 0.05). Pulp treatment in primary molars has
      higher success rate than primary incisors and canines. Composite restorations
      placed in primary canines have low survival rates. The intraexaminer reliability
      was good (k = 0.94). CONCLUSION: The attendance for postoperative follow-up
      appointments declined within two years. Restorative treatment was less successful
      when compared to preventive and pulp treatments. Stainless steel crowns were more
      reliable restorations with higher survival rates and composite restorations were
      less durable.

PMID- 25610914
TI  - Influence of TiO2 nanoparticles on growth and phenolic compounds production in
      photosynthetic microorganisms.
AB  - The influence of titanium dioxide nanoparticles (pure anatase and 15% N doped
      anatase) on the growth of Chlorella vulgaris, Haematococcus pluvialis, and
      Arthrospira platensis was investigated. Results showed that pure anatase can lead
      to a significant growth inhibition of C. vulgaris and A. platensis (17.0 and
      74.1%, resp.), while for H. pluvialis the nanoparticles do not cause a
      significant inhibition. Since in these stress conditions photosynthetic
      microorganisms can produce antioxidant compounds in order to prevent cell
      damages, we evaluated the polyphenols content either inside the cells or released
      in the medium. Although results did not show a significant difference in C.
      vulgaris, the phenolic concentrations of two other microorganisms were
      statistically affected by the presence of titanium dioxide. In particular, 15% N
      doped anatase resulted in a higher production of extracellular antioxidant
      compounds, reaching the concentration of 65.2 and 68.0 mg gDB (-1) for H.
      pluvialis and A. platensis, respectively. 

PMID- 25610915
TI  - Mutant prevention concentrations of imipenem and meropenem against Pseudomonas
      aeruginosa and Acinetobacter baumannii.
AB  - The aim of this study was to determine the usefulness of the MPC of carbapenems
      against clinical isolates of Pseudomonas spp. and Acinetobacter spp. and to
      assess its possible relationship with mechanisms of resistance. Detection of the
      mechanisms of resistance was performed using Antibiotic Susceptibility Testing,
      Double Disk Synergy, disk antagonism, addition of NaCl to the medium, addition of
      PBA or EDTA to Carbapenem disks, addition of PBA to Cefoxitin disks, and CCCP
      test for 10 Pseudomonas spp. and Acinetobacter baumannii strains. The MIC and MPC
      were determined using the broth macrodilution and plate dilution methods,
      respectively. Four Acinetobacter baumannii strains produced MBL. Two of them
      produced Oxacillinase and one produced ESBL. Two Pseudomonas spp. isolates
      produced both KPC and MBL. The resistant Acinetobacter spp. and Pseudomonas spp.
      strains had higher MPC values than susceptible ones. However, the Mutant
      Selection Window was found to be dependent on the degree of resistance but not on
      a particular mechanism of resistance. The usefulness of the MPC was found to be
      dependent on its value. Based on our data, we recommend determining the MPC for
      each isolate before using it during treatment. Furthermore, the use of T>MSW
      instead of T>MIC is suggested. 

PMID- 25610916
TI  - Comparison of Electric Toothbrush, Persica and Chlorhexidine Mouthwashes on
      Reduction of Gingival Enlargement in Orthodontic Patients: A Randomised Clinical
      Trial.
AB  - PURPOSE: To compare the efficacy of chlorhexidine, Persica mouthwash and electric
      toothbrushes in improving gingival enlargement in patients with fixed orthodontic
      appliances. MATERIALS AND METHODS: Seventy-two orthodontic patients with at least
      two sites of gingival enlargement were randomly allocated into four equal groups:
      1) manual toothbrush; 2) electric toothbrush; 3) manual toothbrush+Persica
      mouthwash; 4) manual toothbrush+chlorhexidine mouthwash. All participants were
      instructed to brush their teeth at least twice a day. The subjects in groups 3
      and 4 were instructed to use Persica or chlorhexidine according to the respective
      manufacturer's instructions. Bleeding on probing (BOP) index, gingival index
      (GI), O'Leary's plaque index (PI) and constructed hyperplastic index (HI) of all
      the subjects were measured in a blind manner at the start of the study and 2
      weeks later. Changes of indices in the entire oral cavity and individual affected
      teeth were analysed with SPSS 16 using chi-square, ANOVA, ANCOVA, LSD and the
      paired t-test. RESULTS: In the entire oral cavity, there was a statistically
      significant improvement in indices in all the groups except for HI, which
      significantly improved only in group 4 (p=0.001). Data of individual teeth with
      hyperplastic gingiva showed significant reduction of all the variables except for
      HI in group 1 (p=0.08). No significant differences were found between groups 1
      and 2 or between groups 3 and 4. CONCLUSION: The efficacy of Persica was similar
      to that of chlorhexidine in improving gingival conditions. None of the treatment
      modalities could reduce gingival enlargement to the clinically acceptable level
      of health.

PMID- 25610917
TI  - Relationship Between Oral Health Literacy and Oral Health Status Among College
      Students.
AB  - PURPOSE: To examine the relationship between oral health literacy and oral health
      by adapting a valid oral health literacy instrument. MATERIALS AND METHODS: A
      random sample of 715 students from 9 institutes was included in the study. Oral
      health literacy (OHL) was assessed by making the students pronounce a list of 40
      words from REALD-99. Oral health status (OHL) was assessed using a modified WHO
      (1997) proforma. A stepwise logistic regression analysis was performed to assess
      the impact of independent factors on oral health literacy. RESULTS: The response
      rate was 97.9%; 15 students refused to participate, leaving 700 participants in
      the final sample. The mean age of the participants was 20.35+/-1.66 years. A
      statistically significant difference was observed in OHL according to the
      clinical parameters. Caries prevalence was higher among subjects with low OHL
      with a mean DMFT score of 2.69+/-1.53, compared with high-OHL students having a
      mean DMFT of 0.22+/-0.4. Similarly, oral hygiene status was poor among subjects
      with low OHL (1.53+/-0.6). Community periodontal index (CPI) scores were lower
      (1.06+/-0.8) in subjects with high OHL than in those with low literacy (CPI:
      1.6+/-0.6). CONCLUSION: The present study revealed a negative correlation between
      oral health literacy and clinical parameters measured, that is, higher oral
      health literacy was associated with better oral health.

PMID- 25610918
TI  - Preliminary Clinical Evidence of the Antiplaque, Antigingivitis Efficacy of a
      Mouthwash Containing 2% Green Tea - A Randomised Clinical Trial.
AB  - PURPOSE: To assess the efficacy of a mouthwash containing 2% green tea as
      compared to a placebo mouthwash for the control of plaque and gingivitis.
      MATERIALS AND METHODS: A randomised controlled clinical trial was conducted on
      110 male subjects 18-60 years of age. The inclusion criteria were having a
      minimum of 20 sound natural teeth, a plaque index (PI) of at least 1.5 and a
      gingival index (GI) of at least 1.0. The subjects were randomised into two
      parallel groups, test and control. Subjects in the test group and control group
      were instructed to rinse twice daily for 1 min with 10 ml of test (mouthwash
      containing 2% green tea) and placebo mouthwash, respectively. After 28 days of
      using the mouthwash, inter- and intragroup differences for mean plaque index and
      gingival index scores were analysed. RESULTS: There was a significant (p < 0.05)
      reduction in mean GI and PI scores among the test group from baseline to 28 days,
      whereas it was not significant in the control group. A statistically significant
      (p < 0.05) reduction was found in the mean difference in GI scores in the test
      group (0.67 +/- 0.22) as compared to the control group (0.05 +/- 0.11) and a
      statistically significant (p < 0.05) reduction was observed in the mean
      difference in PI scores in the test group (1.65 +/- 0.68) compared to the control
      group (0.45 +/- 0.99). CONCLUSION: The results showed that the green tea
      mouthwash was effective in the reduction of plaque and gingivitis scores.

PMID- 25610920
TI  - Spectropathology for the next generation: quo vadis?
AB  - Although the potential of vibrational spectroscopy for biomedical applications
      has been well demonstrated, translation into clinical practice has been
      relatively slow. This Editorial assesses the challenges facing the field and the
      potential way forward. While many technological challenges have been addressed to
      date, considerable effort is still required to gain acceptance of the techniques
      among the medical community, standardise protocols, extend to a clinically
      relevant scale, and ultimately assess the health economics underlying clinical
      deployment. National and international research networks can contribute much to
      technology development and standardisation. Ultimately, large-scale funding is
      required to engage in clinical trials and instrument development. 

PMID- 25610919
TI  - Electroanalytical detection of pindolol: comparison of unmodified and reduced
      graphene oxide modified screen-printed graphite electrodes.
AB  - Recent work has reported the first electroanalytical detection of pindolol using
      reduced graphene oxide (RGO) modified glassy carbon electrodes [S. Smarzewska and
      W. Ciesielski, Anal. Methods, 2014, 6, 5038] where it was reported that the use
      of RGO provided significant improvements in the electroanalytical signal in
      comparison to a bare (unmodified) glassy carbon electrode. We demonstrate, for
      the first time, that the electroanalytical quantification of pindolol is actually
      possible using bare (unmodified) screen-printed graphite electrodes (SPEs). This
      paper addresses the electroanalytical determination of pindolol utilising RGO
      modified SPEs. Surprisingly, it is found that bare (unmodified) SPEs provide
      superior electrochemical signatures over that of RGO modified SPEs. Consequently
      the electroanalytical sensing of pindolol is explored at bare unmodified SPEs
      where a linear range between 0.1 MUM-10.0 MUM is found to be possible whilst
      offering a limit of detection (3sigma) corresponding to 0.097 MUM. This provides
      a convenient yet analytically sensitive method for sensing pindolol. The
      optimised electroanalytical protocol using the unmodified SPEs, which requires no
      pre-treatment (electrode polishing) or electrode modification step (such as with
      the use of RGO), was then further applied to the determination of pindolol in
      urine samples. This work demonstrates that the use of RGO modified SPEs have no
      significant benefits when compared to the bare (unmodified) alternative and that
      the RGO free electrode surface can provide electro-analytically useful
      performances. 

PMID- 25610921
TI  - On-surface self-organization of a robust metal-organic cluster based on copper(I)
      with chloride and organosulphur ligands.
AB  - Direct sublimation of a Cu4Cl4 metal-organic cluster on Cu(110) under ultra-high
      vacuum allows the formation of ultra-large well-organized metal-organic
      supramolecular wires. Our results show that the large monomers assemble with each
      other by pi-pi interactions connecting dipyrimidine units and are stabilized by
      the surface. 

PMID- 25610922
TI  - Synthesis of polyfunctional secondary amines by the addition of functionalized
      zinc reagents to nitrosoarenes.
AB  - Addition of functionalized aryl, heteroaryl or adamantyl zinc reagents to various
      nitroso-arenes in the presence of magnesium salts and LiCl in THF produces after
      a reductive work-up with FeCl2 and NaBH4 in ethanol the corresponding
      polyfunctional secondary amines in high yields. 

PMID- 25610923
TI  - (E)-alpha,beta-unsaturated amides from tertiary amines, olefins and CO via Pd/Cu
      catalyzed aerobic oxidative N-dealkylation.
AB  - A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N
      dealkylation/carbonylation reaction has been developed. Tertiary amines are
      utilized as a "reservoir" of "active" secondary amines in this transformation,
      which inhibits the formation of undesired by-products and the deactivation of the
      catalysts. This protocol allows for an efficient and straightforward construction
      of synthetically useful and bioactive (E)-alpha,beta-unsaturated amide
      derivatives from easily available tertiary amines, olefins and CO. 

PMID- 25610924
TI  - A metal-based tumour necrosis factor-alpha converting enzyme inhibitor.
AB  - We report herein a novel iridium(III) complex 1 as an antitumour necrosis factor
      agent and the first metal-based inhibitor of TACE enzymatic activity. Complex 1
      inhibited TNF-alpha secretion and p38 phosphorylation in human monocytic THP-1
      cells.

PMID- 25610925
TI  - Corrigendum to "Prevalence of thermoduric bacteria and spores on 10 Midwest dairy
      farms".
AB  - Thermoduric bacteria (TDB), including sporeformers and their spores, can be
      present in milk and dairy products even after pasteurization. They have the
      potential to adversely affect the quality and shelf life of products. The
      objectives of this study were to identify the origin and common species of heat
      resistant bacteria occurring during summer and winter on Midwest dairy farms.
      Bulk tank milk samples were taken from 10 dairy farms located along the South
      Dakota section of Interstate 29, with herd sizes ranging from 650 to 3,500
      lactating dairy cows. Milk samples were profiled for the prevalence of TDB and
      spore counts (SC). Corn silage samples and swabs of the milking clusters were
      also taken at the dairies to further profile the potential sources of TDB and SC.
      The samples were taken 3 times during 2 seasons [winter (January-March) and
      summer (June-August)] to track seasonal changes in the farm bacterial flora.
      During winter, the average TDB counts in bulk tank milk were 1.83 log compared
      with 1.89 log TDB counts in the summer. The SC was 0.85 log in the winter, which
      was about half the 1.37 log SC present in the summer season. Corn silage sampled
      in winter contained 4.09 log TDB count compared with an increased 5.85 log TDB
      count during summer sampling. Concentrations of SC in corn silage reached an
      average of 3.60 log in winter compared with 6.33 log for summer. The seasonal
      effect was evident with an increase in summer counts across the board for TDB and
      SC, both in the feed and bulk tank milk samples. Bacillus licheniformis was the
      predominant species identified in 62.4% of winter (85 total) and 49.4% of summer
      (83 total) samples. Bacillus subtilis made up 9.4% of the remaining winter
      isolates, followed by Bacillus sonorensis at 8.2%. Conversely, B. sonorensis made
      up 12% of the summer isolates followed by Bacillus pumilus at 10.8%. Bacillus
      licheniformis is a ubiquitous microbe and was isolated from both TDB and
      sporeformer categories in all 3 sample types. There were larger increases in SC
      than TDB, indicating that summer temperatures and conditions may favor
      proliferation of sporeforming bacteria over that of TDB. In conclusion, samples
      from bulk tank milk, milking cluster swabs, and corn silage samples at each of
      the 10 sites indicated that B. licheniformis was the major contaminant species,
      regardless of season. In this experiment, corn silage was the major environmental
      source of both TDB and SC with higher concentrations in summer when compared with
      winter.

PMID- 25610926
TI  - Sol "Bud" Silverman, Jr., MA, DDS  May 12, 1926 - August 13, 2014.

PMID- 25610927
TI  - Retracted: The oncogenic effects of constitutive Stat3 signaling in salivary
      gland cancer cells are mediated by survivin and modulated by the NSAID sulindac.

PMID- 25610928
TI  - Comment on "Percutaneous coronary intervention with everolimus-eluting
      bioabsorbable vascular scaffolds in routine clinical practice: early and midterm
      outcomes from the European multicentre GHOST-EU registry".

PMID- 25610929
TI  - Retraction notice to "Acetyl-11-keto-beta-boswellic acid (AKBA) prevents human
      colonic adenocarcinoma growth through modulation of multiple signaling pathways"
      Biochimica et Biophysica Acta [1830 (10) 4907-4916].

PMID- 25610930
TI  - Retraction notice to "Acetyl-11-beta-boswellic acid (AKBA)inhibits human gastric
      carcinoma growth through modulation of the Wnt/beta-canetin signalin pathway"
      Biochimica et Biophysica Acta [1830 (6) 3604-3615].

PMID- 25610931
TI  - How wild do you want to go?
AB  - Urbanisation, efficiency improvement in agriculture, and the transition to a post
      industrial economy in Europe and North America has taken large areas of land out
      of human use that could be returned to a 'natural' state. But what exactly is
      natural, and how much or how little ecosystem engineering should be involved in
      rewilding efforts? Michael Gross reports.

PMID- 25610932
TI  - Bob Steneck.

PMID- 25610933
TI  - [In Process Citation].

PMID- 25610944
TI  - Metal matrix-metal nanoparticle composites with tunable melting temperature and
      high thermal conductivity for phase-change thermal storage.
AB  - Phase-change materials (PCMs) are of broad interest for thermal storage and
      management applications. For energy-dense storage with fast thermal
      charging/discharging rates, a PCM should have a suitable melting temperature,
      large enthalpy of fusion, and high thermal conductivity. To simultaneously
      accomplish these traits, we custom design nanocomposites consisting of phase
      change Bi nanoparticles embedded in an Ag matrix. We precisely control
      nanoparticle size, shape, and volume fraction in the composite by separating the
      nanoparticle synthesis and nanocomposite formation steps. We demonstrate a 50
      100% thermal energy density improvement relative to common organic PCMs with
      equivalent volume fraction. We also tune the melting temperature from 236-252 
      degrees C by varying nanoparticle diameter from 8.1-14.9 nm. Importantly, the
      silver matrix successfully prevents nanoparticle coalescence, and no melting
      changes are observed during 100 melt-freeze cycles. The nanocomposite's Ag matrix
      also leads to very high thermal conductivities. For example, the thermal
      conductivity of a composite with a 10% volume fraction of 13 nm Bi nanoparticles
      is 128 +/- 23 W/m-K, which is several orders of magnitude higher than typical
      thermal storage materials. We complement these measurements with calculations
      using a modified effective medium approximation for nanoscale thermal transport.
      These calculations predict that the thermal conductivity of composites with 13 nm
      Bi nanoparticles varies from 142 to 47 W/m-K as the nanoparticle volume fraction
      changes from 10 to 35%. Larger nanoparticle diameters and/or smaller nanoparticle
      volume fractions lead to larger thermal conductivities. 

PMID- 25610945
TI  - A new flavonol triglycoside derived from Anoectochilus elwesii on stimulating
      glucose uptake in insulin-induced human HepG2 cells.
AB  - A novel flavonol triglycoside (4), isorhamnetin-3-O-beta-D-glucopyranosyl (1->2)
      alpha-L-rhamnopyranosyl (1->6)-beta-D-glucopyranoside, named elwesoside A,
      together with six known flavonols (1-3, 5-7) was isolated from Anoectochilus
      elwesii (Clarke ex Hook. f.) King et Pantl. and its structure was elucidated by
      extensive spectroscopic methods and comparison with the literature data. All
      compounds were first reported in this plant and two of them (4 and 5) were the
      first examples of flavonol triglycosides isolated from Anoectochilus genus. The
      effects of 1-7 were evaluated on insulin-treated human HepG2 cells under high
      glucose conditions for stimulating glucose uptake activities. The novel compound
      (4) displayed highly potent dose-dependent effect on the stimulation of glucose
      uptake in insulin-resistant human HepG2 cells.

PMID- 25610946
TI  - Dexamethasone Intravitreal Implant for Chronic Diabetic Macular Edema Resistant
      to Intravitreal Bevacizumab Treatment.
AB  - PURPOSE: To evaluate the safety and efficacy of intravitreal dexamethasone
      implant (Ozurdex) in patients with chronic diabetic macular edema (DME) resistant
      to prior intravitreal bevacizumab (IVB) treatment. MATERIALS AND METHODS: Thirty
      eyes of 30 patients were administered intravitreal Ozurdex and examined at
      baseline and 1, 3, and 6 months postinjection in this prospective study. Main
      outcomes were the best corrected visual acuity (BCVA, logMAR), central foveal
      thickness (CFT), mean cube volume (MCV), and intraocular pressure (IOP). Patients
      had a CFT over 275 um (measured by OCT) and were unresponsive to 3 consecutive
      IVB injections. All data are presented as mean +/- standard deviation. RESULTS:
      The mean BCVA significantly increased from 0.56 +/- 0.38 to 0.41 +/- 0.27 (p <
      0.001), and 0.44 +/- 0.28 (p = 0.008) at 1 and 3 months, respectively. At months
      1, 3, and 6, the mean CFT significantly decreased from 517 +/- 136 um at
      baseline, to 290 +/- 60 um (p < 0.001), 314 +/- 88 um (p < 0.001) and 411 +/- 126
      um (p = 0.01), respectively. However, the mean CFT (p < 0.001) and MCV (p = 0.01)
      significantly increased and BCVA significantly decreased (p = 0.04) at 6 month
      compared to 3 month. Compared to baseline, IOP increased significantly at 1 week
      (p = 0.01), 1 month (p = 0.01) and 3 months (p = 0.04). However eyes with IOP
      higher than 21 mmHg were treated and well controlled with topical anti-glaucoma
      monotherapy. Macular edema recurrence occurred in 25 eyes (CFT ranged from 321 um
      to 800 um) at 6 months. CONCLUSION: Dexamethasone intravitreal implant may be an
      effective and safe alternative in treatment of chronic DME nonresponsive to
      regular IVB. However, its therapeutic efficacy decreases between the third and
      sixth months following the injection.

PMID- 25610947
TI  - Self-assembled supramolecular nanoprobes for ratiometric fluorescence measurement
      of intracellular pH values.
AB  - Self-assembly of small building blocks into functional supramolecular
      nanostructure has opened prospects for the design of novel materials. With this
      molecular engineering strategy, we have developed self-assembled supramolecular
      nanoprobes (SSNPs) for ratiometric fluorescence measurement of pH values in
      cells. The nanoprobes with a diameter of ~30 nm could be formulated just by
      mixing pH-sensitive adamantane-fluorescein (Ad-F) and pH-insensitive adamantane
      Rhodamine B (Ad-R) with beta-cyclodextrin polymer (poly-beta-CD) at one time. The
      nanoprobes with good biocompatibility have been successfully applied to measure
      intracellular pH in the pH range of 4-8 and estimate pH fluctuations associated
      with different stimuli in cells. Moreover, we expect that this self-assembled
      approach is applicable to the construction of nanoprobes for other targets in
      cells just by replacing the respective indicator dyes with relevant indicators. 

PMID- 25610948
TI  - Optical sensor nanoparticles in artificial sediments--a new tool to visualize O2
      dynamics around the rhizome and roots of seagrasses.
AB  - Seagrass communities provide important ecosystems services in coastal
      environments but are threatened by anthropogenic impacts. Especially the ability
      of seagrasses to aerate their below-ground tissue and immediate rhizosphere to
      prevent sulfide intrusion from the surrounding sediment is critical for their
      resilience to environmental disturbance. There is a need for chemical techniques
      that can map the O2 distribution and dynamics in the seagrass rhizosphere upon
      environmental changes and thereby identify critical stress thresholds of e.g.
      water flow, turbidity, and O2 conditions in the water phase. In a novel
      experimental approach, we incorporated optical O2 sensor nanoparticles into a
      transparent artificial sediment matrix consisting of pH-buffered deoxygenated
      sulfidic agar. Seagrass growth and photosynthesis was not inhibited in the
      experimental setup when the below-ground biomass was immobilized in the
      artificial sulfidic sediment with nanoparticles and showed root growth rates (~ 5
      mm day(-1)) and photosynthetic quantum yields (~ 0.7) comparable to healthy
      seagrasses in their natural habitat. We mapped the real-time below ground O2
      distribution and dynamics in the whole seagrass rhizosphere during experimental
      manipulation of light exposure and O2 content in the overlaying water. Those
      manipulations showed that oxygen release from the belowground tissue is much
      higher in light as compared to darkness and that water column hypoxia leads to
      diminished oxygen levels around the rhizome/roots. Oxygen release was visualized
      and analyzed on a whole rhizosphere level, which is a substantial improvement to
      existing methods relying on point measurements with O2 microsensors or partial
      mapping of the rhizosphere in close contact with a planar O2 optode. The combined
      use of optical nanoparticle-based sensors with artificial sediments enables
      imaging of chemical microenvironments in the rhizosphere of aquatic plants at
      high spatiotemporal resolution with a relatively simple experimental setup and
      thus represents a significant methodological advancement for studies of
      environmental impacts on aquatic plant ecophysiology.

PMID- 25610949
TI  - Spin-state ordering in hydroxo-bridged diiron(III)bisporphyrin complexes.
AB  - We report the synthesis, structure, and spectroscopic characterization of 1,2
      bis[MU-hydroxo iron(III) 5-(2,3,7,8,12,13,17,18-octaethylporphyrinyl)]ethane with
      PF6(-) and SbF6(-) counteranions. The two iron centers are nonequivalent with
      admixed intermediate spin state (S = 3/2 with a minor contribution of S = 5/2) on
      each metal both in the solid and in solution. The molecules are compared with
      previously known MU-hydroxo complexes with other counterions, such as I3(-), BF4(
      ), and ClO4(-), which demonstrates that the nature of the counterion can affect
      the spin-state ordering dramatically. To understand how the spin-state ordering
      is affected by external perturbations, we also have done a comprehensive
      computational study. The calculations show that subtle environmental
      perturbations affect the spin-state ordering and relative energies and are likely
      to be the root cause of the variation in spin-state ordering observed
      experimentally.

PMID- 25610950
TI  - Calcitriol exerts anti-inflammatory effects in keratinocytes treated with
      autoantibodies from a patient with bullous pemphigoid.
AB  - BACKGROUND: The hormonally active vitamin D metabolite calcitriol and its
      analogues exert potent effects on cellular differentiation and regulation of
      immune responses. Although topical vitamin D analogues are widely used for
      treatment of psoriasis and vitamin D has been increasingly implicated in
      prevention and protection from several autoimmune diseases, experimental and
      clinical data in autoimmune bullous diseases are generally lacking. OBJECTIVE:
      Here, we investigated the effects of calcitriol on keratinocytes treated by
      bullous pemphigoid (BP) autoantibodies. METHODS: Human keratinocyte (HaCaT) cells
      were treated with purified human BP or normal IgG from one BP patient and healthy
      subject, respectively, in the absence or presence of calcitriol and effects on
      (i) cell viability, (ii) IL-6 and IL-8 secretion, (iii) STAT3 and NFkappaB
      activation, (iv) heat shock protein 70 (Hsp70) level, and (v) vitamin D receptor
      (VDR) expression were studied. RESULTS: We found that BP IgG-induced IL-6 and IL
      8 release from HaCaT cells was reduced in the presence of non-toxic doses of
      calcitriol. Additionally, calcitriol blunted BP IgG-mediated STAT3
      phosphorylation and NFkappaB activity, whereas Hsp70 and VDR expression were not
      affected. CONCLUSION: Although the results of this study are based on
      autoantibodies prepared from a single patient, they show that calcitriol protects
      from BP IgG-induced inflammatory processes in vitro, thus favouring its potential
      inclusion into the therapeutic repertoire of BP.

PMID- 25610951
TI  - Sedentary behavior is associated with disability status and walking performance,
      but not cognitive function, in multiple sclerosis.
AB  - Eighty-two persons with multiple sclerosis wore an accelerometer as a measure of
      sedentary time (min/day) and completed measures of disability status (self
      reported Expanded Disability Status Scale), walking performance (timed 25-foot
      walk and 6-min walk), and cognitive function (symbol digit modalities test).
      Accelerometry-measured sedentary time was significantly correlated with
      disability status scores (r = 0.31, p < 0.01), 6-min walk distance (r = -0.40, p
      < 0.01), and timed 25-foot walk performance (r = 0.35, p < 0.01), but not
      cognitive function performance (r = -0.12, p = 0.29). 

PMID- 25610952
TI  - Mealtime exposure to food advertisements while watching television increases food
      intake in overweight and obese girls but has a paradoxical effect in boys.
AB  - Food advertisements (ads) in TV programs influence food choice and have been
      associated with higher energy intake from snacks in children; however, their
      effects at mealtime have not been reported. Therefore, we measured energy intake
      at a pizza meal consumed by normal weight (NW) and overweight/obese (OW/OB)
      children (aged 9-14 years) while they watched a TV program with or without food
      ads and following pre-meal consumption of a sweetened beverage with or without
      calories. NW and OW/OB boys (experiment 1, n = 27) and girls (experiment 2, n =
      23) were randomly assigned to consume equally sweetened drinks containing glucose
      (1.0 g/kg body weight) or sucralose (control). Food intake was measured 30 min
      later while children watched a program containing food or nonfood ads. Appetite
      was measured before (0-30 min) and after (60 min) the meal. Both boys and girls
      reduced energy intake at the meal in compensation for energy in the glucose
      beverage (p < 0.05). Food ads resulted in further compensation (51%) in boys but
      not in girls. Food ads increased energy intake at the meal (9%; p = 0.03) in
      OW/OB girls only. In conclusion, the effects of TV programs with food ads on
      mealtime energy intake and response to pre-meal energy consumption in children
      differ by sex and body mass index. 

PMID- 25610953
TI  - Energy requirements and the use of predictive equations versus indirect
      calorimetry in critically ill patients.
AB  - Nutrition support has been shown to have a positive impact on critically ill
      patients who meet their defined goals of nutrition therapy. However,
      inappropriate energy assessment can contribute to under- or overfeeding resulting
      in deleterious effects. Thus, assessment of energy expenditure in critically ill
      patients is crucial to prevent negative impacts from inappropriate feeding.
      Currently, the optimal energy requirement and appropriate energy assessment in
      these patients is controversial. Indirect calorimetry or predictive equations
      have been suggested to evaluate energy expenditure in critically ill patients.
      Indirect calorimetry is a gold standard for evaluating energy expenditure, but it
      is not always available and has some limitations. Many predictive equations,
      therefore, have been developed to predict energy expenditure in critically ill
      patients. However, these equations cannot be used generally in these patients
      since they were developed in a unique patient population. Many studies compared
      measured energy expenditure with predictive energy expenditure, but the data
      regarding accuracy is not robust. Therefore, clinicians should consider using
      these equations carefully based on the current supporting data. Indirect
      calorimetry is recommended for use in evaluating energy expenditure in critically
      ill patients if it is available. 

PMID- 25610954
TI  - Daily chocolate milk consumption does not enhance the effect of resistance
      training in young and old men: a randomized controlled trial.
AB  - Older and younger men completed 12 weeks of resistance training and ingested
      either 500 mL of chocolate milk or placebo daily. Training increased strength in
      both age groups (p < 0.05), with no supplementation effect. Type I muscle fibre
      area increased with training (p = 0.008) with no effect of age or
      supplementation. Type II fibre area increased (p = 0.014) in young men only with
      no supplementation effect. Chocolate milk did not enhance skeletal muscle
      hypertrophy following training. 

PMID- 25610955
TI  - Design, synthesis, and structure-activity relationship of novel LSD1 inhibitors
      based on pyrimidine-thiourea hybrids as potent, orally active antitumor agents.
AB  - Histone lysine specific demethylase 1 (LSD1) was reported to be overexpressed in
      several human cancers and recognized as a promising anticancer drug target. In
      the current study, we designed and synthesized a novel series of pyrimidine
      thiourea hybrids and evaluated their potential LSD1 inhibitory effect. One of the
      compounds, 6b, containing a terminal alkyne appendage, was shown to be the most
      potent and selective LSD1 inhibitor in vitro and exhibited strong cytotoxicity
      against LSD1 overexpressed gastric cancer cells. Compound 6b also showed marked
      inhibition of cell migration and invasion as well as significant in vivo tumor
      suppressing and antimetastasis role, without significant side effects by oral
      administration. Our findings indicate that the pyrimidine-thiourea-based LSD1
      inactivator may serve as a leading compound targeting LSD1 overexpressed cancers.

PMID- 25610956
TI  - Electric field changes on Au nanoparticles on semiconductor supports--the
      molecular voltmeter and other methods to observe adsorbate-induced charge
      transfer effects in Au/TiO2 nanocatalysts.
AB  - Infrared (IR) studies of Au/TiO2 catalyst particles indicate that charge transfer
      from van der Waals-bound donor or acceptor molecules on TiO2 to or from Au occurs
      via transport of charge carriers in the semiconductor TiO2 support. The DeltanuCO
      on Au is shown to be proportional to the polarizability of the TiO2 support fully
      covered with donor or acceptor molecules, producing a proportional frequency
      shift in nuCO. Charge transfer through TiO2 is associated with the population of
      electron trap sites in the bandgap of TiO2 and can be independently followed by
      changes in photoluminescence intensity and by shifts in the broad IR absorbance
      region for electron trap sites, which is also proportional to the polarizability
      of donors by IR excitation. Density functional theory calculations show that
      electron transfer from the donor molecules to TiO2 and to supported Au particles
      produces a negative charge on the Au, whereas the transfer from the Au particles
      to the TiO2 support into acceptor molecules results in a positive charge on the
      Au. These changes along with the magnitudes of the shifts are consistent with the
      Stark effect. A number of experiments show that the ~3 nm Au particles act as
      "molecular voltmeters" in influencing DeltanuCO. Insulator particles, such as
      SiO2, do not display electron-transfer effects to Au particles on their surface.
      These studies are preliminary to doping studies of semiconductor-oxide particles
      by metal ions which modify Lewis acid/base oxide properties and possibly strongly
      modify the electron-transfer and catalytic activity of supported metal catalyst
      particles. 

PMID- 25610958
TI  - Mary Shelley's Frankenstein: what made the Monster monstrous?
AB  - This paper discusses the genesis of the famous story of Frankenstein which arose
      from a dream experienced by Mary Shelley whilst on a holiday shared with her
      husband Percy Shelley, Lord Byron, Dr Polidori and her step sister Claire
      Clairmont. The novel relates how the creature created by Victor Frankenstein
      horrifies him, is rejected by him and called a monster. The monster's ensuing
      despair and subsequent murderousness is eloquently described. The whole book is
      clearly connected to Mary Shelley's experience as an infant whose mother died
      after giving birth to her and her subsequent loss, as a mother, of her own new
      born infant. It is suggested that the novel imaginatively describes what it is to
      have been primarily rejected as an infant and to feel regarded as a monster. 

PMID- 25610957
TI  - Characterization of co-purified acellular pertussis vaccines.
AB  - Whole-cell pertussis vaccines (WPVs) have been completely replaced by the co
      purified acellular vaccines (APVs) in China. To date few laboratory studies were
      reported for co-purified APVs in terms of their antigenic composition and
      protective immune responses. To further understand the antigenic composition in
      co-purified APVs, in the present study 2-dimensional gel electrophoresis-based
      proteomic technology was used to analyze the composition of co-purified APVs. The
      results showed that besides the main antigens pertussis toxin (PT) and
      filamentous hemagglutinin (FHA), co-purified APVs also contained pertactin (PRN),
      fimbriae (FIM) 2and3 and other minor protein antigens. Of the 9 proteins
      identified, 3 were differentially presented in products from manufacturer 1 and
      manufacturer 2. Compared with WPVs and purified APVs, co-purified APVs induced a
      mixed Th1/Th2 immune response with more toward to a Th1 response than the
      purified APVs in this study. These results hint that different immune mechanisms
      might be involved in protection induced by co-purified and purified APVs. 

PMID- 25610959
TI  - Winnicott's invitation to 'further games of Jung-analysis'.
AB  - Winnicott signs off his celebrated review of Jung's (1963) autobiography
      Memories, Dreams, Reflections with the warning that translation of 'erreichten'
      as 'attained' (implying assimilation) rather than as 'reached to', could 'queer
      the pitch for further games of Jung-analysis'. This subtly underscores his view
      that Jung--who he described earlier as 'mentally split' and lacking 'a self with
      which to know'--remained essentially dissociated. However, Winnicott, whilst
      immersed in this work on Jung, wrote a letter to Michael Fordham describing
      himself as suffering 'a lifelong malady' of 'dissociation'. But this he now
      reported repaired through a 'splitting headache' dream of destruction, dreamt
      'for Jung, and for some of my patients, as well as for myself' (Winnicott 1989,
      p. 228). Winnicott's recurrent concern during his last decade was with 'reaching
      to'--that quintessential Winnicottian term--some reparative experience that could
      address such difficulties in constellating a 'unit self'. This is correlated with
      his engagement with Jung and tracked through his contemporaneous clinical work,
      particularly 'Fear of Breakdown' (1963). Themes first introduced by Sedgwick
      (2008) and developed by the author's earlier 'Winnicott on Jung; destruction,
      creativity and the unrepressed unconscious' (2011) are given further
      consideration.

PMID- 25610960
TI  - Sandplay therapy with couples within the framework of analytical psychology.
AB  - Sandplay therapy with couples is discussed within an analytical framework.
      Guidelines are proposed as a means of developing this relatively new area within
      sandplay therapy, and as a platform to open a wider discussion to bring together
      sandplay therapy and couple therapy. Examples of sand trays created during couple
      therapy are also presented to illustrate the transformations during the
      therapeutic process. 

PMID- 25610961
TI  - States of grace: Eureka moments and the recognition of the unthought known.
AB  - In this paper we consider states of grace in analysis. These encompass a range of
      phenomena which share an experience of something being received or revealed
      rather than produced by the ego. It feels that they are events that happen rather
      than events that are made to occur. They are marked by a profound sense of
      transformation of feeling tone. The quality of relatedness in the analytic dyad
      is also heightened. Some of these phenomena have been referred to as experiences
      of the self, synchronicities, moments of meeting, the unthought known and Eureka
      moments. The latter are experiences of sudden realization where a meaningful
      thought or image emerges which results in a dramatic shift in direction of the
      analysis and a transcendence of impasse. Although many authors describe these
      phenomena, we find that a Jungian approach provides a loom on which these threads
      can be woven together. Jung's concept of the transcendent function and his
      understanding of the gift of grace are particularly illuminating here. We also
      consider the conditions which allow grace to be experienced and how these inform
      our analytic practice. 

PMID- 25610962
TI  - Conspiracies of immanence: Paul Tillich, Pierre Teilhard de Chardin and C.G.
      Jung.
AB  - Jung's psychology proffers a sustained reflection on the traditional religious
      question of the relation of divine transcendence to immanence. On this issue his
      psychology affirms a position of radical immanence in its contention that the
      experience of divinity is initially wholly from within. Though this position
      remains on the periphery of religious and theological orthodoxy Jung is not alone
      in holding it among moderns. Paul Tillich adopts a similar stance with his
      controlling symbols of the divine as 'Ground of Being' and 'Depth of Reason'.
      Pierre Teilhard de Chardin understands divinity as the experiential energy of
      evolution itself working within nature and humanity toward greater configurations
      of universal communion as the basis of community. All of Jung's master symbols of
      individuation assume such an understanding of immanence uniting individual and
      totality. His psychology strongly suggests and contributes to the current
      emergence of a new religious sensitivity based on the awareness of the intra
      psychic origin of all religions. In his later writings he held out such a
      position as a significant alternative to genocide. 

PMID- 25610963
TI  - Another serious misunderstanding: Jung, Giegerich and a premature requiem.
AB  - Barreto's paper, 'Requiem for analytical psychology' utilized Jung's dreams and
      visions to argue for the obsolescence of Jungian psychology. Its thesis rested
      upon the theoretical assumptions of Giegerich's psychology as a Discipline of
      Interiority, which he and Giegerich claim are themselves based in Jung's
      psychology. Here I argue that that claim is misplaced because it depends upon a
      fundamental misunderstanding of the nature of Jung's psychological project. I
      shall further argue that Giegerich's arguments for a Jungian basis to his
      psychology rely upon misreadings and decontextualisations of Jung's original
      texts. Finally, I shall attempt to draw attention to the weaknesses and
      contradictions involved in Barreto's interpretations of Jung's dreams and
      visions. 

PMID- 25610964
TI  - Another serious misunderstanding, indeed! a response to Mark Saban.

PMID- 25610965
TI  - Some reflections on Barreto's response.

PMID- 25610966
TI  - Attentive notice to a reply of Harald Atmanspacher (JAP, 59, 3, 429-434).

PMID- 25610967
TI  - Film and culture.

PMID- 25610968
TI  - Analytical psychology and cinema.

PMID- 25610977
TI  - Pathogenesis of atopic dermatitis.
AB  - Atopic dermatitis (AD) is the most common allergic inflammatory skin disease.
      Interactions of genetic, environmental and immunological factors result in the
      initiation and progress of AD. Although the clinical picture, characterized by
      acute flare-ups of eczematous, pruritic lesions on dry skin at typical
      predilection such as the flexural folds, is quite homogenous, the trigger factors
      of the disease are diverse and the pathophysiologic network involved is complex.
      Therefore, first attempts have been made to classify subtypes of AD based on the
      most relevant causal factors in the individual patient. To optimize such a
      stratification of patients, detailed knowledge about cofactors impacting on
      manifestation of AD as well as impairment of the course of the disease is
      indispensable. AD shares general features of barrier dysfunction and skin
      inflammation with other inflammatory diseases of the skin such as psoriasis or
      allergic contact dermatitis, but a plethora of disease-specific genetic,
      immunologic and environmental factors have been identified in AD as well. It is
      the purpose of this review to illustrate key concepts of the pathogenesis of AD.
      Important findings of recent years will be summarized and cofactors of the
      pathogenesis will be controversially discussed. We will summarize knowledge on
      pathogenic factors on the immunologic level contributing to skin barrier
      dysfunction in AD and the role of the microbiome as first line of defence.
      Furthermore, we will elucidate the role of innate lymphoid cells in AD and
      outline the pattern of T helper cell subtypes present in the skin during
      different stages of AD. 

PMID- 25610979
TI  - Pseudoempyema in an Indigenous Australian child: occurring via a rare route.

PMID- 25610978
TI  - RNA synthesis by in vitro selected ribozymes for recreating an RNA world.
AB  - The RNA world hypothesis states that during an early stage of life, RNA molecules
      functioned as genome and as the only genome-encoded catalyst. This hypothesis is
      supported by several lines of evidence, one of which is the in vitro selection of
      catalytic RNAs (ribozymes) in the laboratory for a wide range of reactions that
      might have been used by RNA world organisms. This review focuses on three types
      of ribozymes that could have been involved in the synthesis of RNA, the core
      activity in the self-replication of RNA world organisms. These ribozyme classes
      catalyze nucleoside synthesis, triphosphorylation, and the polymerization of
      nucleoside triphosphates. The strengths and weaknesses regarding each ribozyme's
      possible function in a self-replicating RNA network are described, together with
      the obstacles that need to be overcome before an RNA world organism can be
      generated in the laboratory. 

PMID- 25610980
TI  - Excessive daytime sleepiness in adult patients with ADHD as measured by the
      Maintenance of Wakefulness Test, an electrophysiologic measure.
AB  - OBJECTIVE: To quantify the objective level of sleepiness in adult attention
      deficit/hyperactivity disorder (ADHD) patients and to determine the relationship
      between excessive daytime sleepiness and simulated driving performance. METHOD:
      Forty adult ADHD patients (DSM-IV criteria) and 19 matched healthy control
      subjects were included between June 30, 2010, and June 19, 2013. All participants
      completed the Epworth Sleepiness Scale and the Manchester Driving Behavior
      Questionnaire. After nocturnal polysomnography, they performed 2
      neuropsychological tests, a 4 * 40-minute Maintenance of Wakefulness Test, and a
      1-hour driving session. The primary outcome measure was the mean sleep latency on
      the Maintenance of Wakefulness Test. ADHD patients were divided into 3 groups
      defined by their Maintenance of Wakefulness Test scores. Participants (patients
      and control subjects) were allocated as follows: sleepy ADHD (0-19 min),
      intermediate ADHD (20-33 min), alert ADHD (34-40 min), and control group (34-40
      min). The driving performance outcome was the mean standard deviation of lateral
      position of the vehicle during the simulated session. RESULTS: The group mean
      (SD) Epworth Sleepiness Scale score was higher in ADHD patients (12.1 [4.4]) than
      in controls (6.0 [2.7]) (P < .001). On the basis of the Maintenance of
      Wakefulness Test scores, 14 patients (35%) were in the sleepy group, 20 (50%)
      were in the intermediate group, and only 6 (15%) were in the alert group. Sleepy
      ADHD patients exhibited significantly deteriorated driving performance compared
      to the other 3 groups (P < .01). CONCLUSIONS: Our study shows that a significant
      proportion of adult ADHD patients exhibit an objective excessive daytime
      sleepiness, which, in addition, has an impact on simulated driving performance.
      Excessive daytime sleepiness, therefore, may be a key element needed to better
      evaluate these ADHD patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01160874.

PMID- 25610982
TI  - A variation in the course of the hypoglossal nerve.

PMID- 25610983
TI  - Opportunities for certificate of completion of training.

PMID- 25610984
TI  - Objective measurement of the external nasal valve.

PMID- 25610985
TI  - Response to 'Thorascopic ligation of the thoracic duct complex in the treatment
      for high-volume chyle leak following modified radical neck dissection: safe,
      feasible, but underutilized' (Volume 39, Issue 1, pages 73-74, 2014).

PMID- 25610986
TI  - Application of phenol as topical anaesthesia using the Derlacki elevator for
      myringotomy. [corrected].

PMID- 25610988
TI  - Endoscopic transethmoidal approach for removal of intraconal hemangiomas using an
      autostatic retractor for exposure--technical note.

PMID- 25610989
TI  - Mammalian cell cryopreservation by using liquid marbles.
AB  - Liquid marbles (LMs) are nonsticky droplets covered by micro- or nanometrically
      scaled particles and obtained by simply rolling small amounts of a liquid in a
      very hydrophobic powder. Since pioneer work by Aussillous and Quere, a wide
      palette of hydrophobic materials for the preparation of LMs, as well as potential
      applications, have been reported. Because of the bioinspired origin of this
      concept, the applicability of LMs in biomedicine is gaining increasing attention,
      with remarkable advances in their use as microbioreactors for blood typing, drug
      screening, and tumor growth, among others. Herein, we explore the novel use of
      LMs as a biotechnological tool for the cryopreservation of mammalian cells as an
      alternative to conventional methods, which typically require the use of
      cryopreservant agents that commonly associate with some degree of cell toxicity.
      Murine L929 fibroblasts, a reference cell line for cytotoxicity studies, and
      poly(tetrafluoroethylene), a hydrophobic polymer widely used in cardiovascular
      surgery, were selected for the preparation of the cell-containing LMs. Our
      results reveal that there is a safe range of droplet volumes and cell densities
      that can be successfully used to cryopreserve mammalian cell lines and recover
      them after thawing without significantly affecting major cellular parameters such
      as adhesion, morphology, viability, proliferation, and cell cycle. We envision
      that progress in the exploration of cell-containing LMs could also open their
      impact as microreactors for the miniaturization of cytotoxicity procedures of
      drugs and materials in which powerful tools for cell evaluation such as flow
      cytometry could be used because of the elevated amount of cells handled. 

PMID- 25610990
TI  - Functional mobility in a divided attention task in older adults with cognitive
      impairment.
AB  - Motor disorders may occur in mild cognitive impairment (MCI) and at early stages
      of Alzheimer's disease (AD), particularly under divided attention conditions. We
      examined functional mobility in 104 older adults (42 with MCI, 26 with mild AD,
      and 36 cognitively healthy) using the Timed Up and Go test (TUG) under 4
      experimental conditions: TUG single task, TUG plus a cognitive task, TUG plus a
      manual task, and TUG plus a cognitive and a manual task. Statistically
      significant differences in mean time of execution were found in all four
      experimental conditions when comparing MCI and controls (p < .001), and when
      comparing MCI and AD patients (p < .05). Receiver-operating characteristic curve
      analyses showed that all four testing conditions could differentiate the three
      groups (area under the curve > .8, p < .001 for MCI vs. controls; area under the
      curve > .7, p < .001 for MCI vs. AD). The authors conclude that functional motor
      deficits occurring in MCI can be assessed by the TUG test, in single or dual task
      modality. 

PMID- 25610991
TI  - Fossils reject climate change as the cause of extinction of Caribbean bats.
AB  - We combined novel radiocarbon dates of bat fossils with time-scaled ecological
      niche models (ENM) to study bat extinctions in the Caribbean. Radiocarbon-dated
      fossils show that late Quaternary losses of bat populations took place during the
      late Holocene (<4 ka) rather than late Pleistocene (>10 ka). All bat radiocarbon
      dates from Abaco (Bahamas) that represent extirpated populations are younger than
      4 ka. We include data on six bat species, three of which are Caribbean endemics,
      and include nectarivores as well as insectivores. Climate-based ENMs from the
      Last Glacial Maximum to the present reflect overall stability in distributions,
      with suitable climatic habitat being present over time. In the absence of
      radiocarbon dates, bat extinctions had been presumed to take place during the
      last glacial-interglacial transition (ca. 10 ka). Now we see that extirpation of
      bats on these tropical islands is more complex than previously thought and
      primarily postdates the major climate changes that took place during the late
      Pleistocene-Holocene transition. 

PMID- 25610993
TI  - Potentials with potential.

PMID- 25610994
TI  - Should we extend the indications for therapeutic hypothermia?

PMID- 25610995
TI  - Children and media: new challenges call for interdisciplinary and comparative
      approaches.

PMID- 25610996
TI  - Self-awareness - an emerging field in neurobiology.

PMID- 25610997
TI  - Optimum Function in Patients With Heart Failure.
AB  - PURPOSE: The aim of this article is to use Walker and Avant's methodological
      approach to provide clarity and a definition of optimum function as it relates to
      patients with heart failure (HF). BACKGROUND: Understanding optimum function in
      patients with HF can help advanced practice nurses (APNs) identify clinical signs
      of deterioration. Interpreting patient descriptions of signs and symptoms may be
      the first cues prior to diagnosis. DATA SOURCE: Literature searches included
      electronic scientific databases and a manual search. Literature from 2005 to 2013
      was reviewed. Themes were searched for function. The text was limited to English
      language peer-reviewed articles, resulting in 43 articles and 3 books in the
      analysis. CONCLUSION: A definition of optimum function was developed from a
      synthesis of the literature's common themes. The four defining attributes
      include: multidimensional aspect (physical, cognitive, psychosocial,
      physiological, and spiritual), achieving a desired goal, dynamic and relative
      change (compared with previous functioning), and most favorable level of
      functioning. Defining optimum function in patients with HF provides clarity of
      patient communication to and between APNs. The concept promotes patient-centered
      care, enabling goal adjustment by the patient and APN. The concept analysis
      facilitates a deeper understanding of communication during the patient encounter.

PMID- 25610998
TI  - Integrin-based therapy of pancreatic adenocarcinoma: current status and future
      perspectives.
AB  - Pancreatic ductal adenocarcinoma (PDAC), although tenth in cancer incidence,
      holds the dubious distinction of being the fifth cause of cancer deaths in the
      Western countries and possibly the deadliest malignancy. Inoperable PDAC is
      characterized by late diagnosis, extensive metastases, extremely poor response to
      chemotherapy and, consequently, poor patients' prognosis-6.7% 5-year survival.
      PDAC reflects the failure of the medical profession to significantly prolong
      patients' lives and modest expectations for future cure. PDAC is characterized by
      extensive desmoplastic reaction, resulting in approximately 50% of tumor's volume
      consisting of non-tumor cells and extracellular matrix (ECM) stroma. These
      properties imply an important role for cell-ECM interaction, making cell-matrix
      adhesion molecules, such as integrins, of special interest as possible candidate
      targets for future anti-PDAC therapies. This review will attempt to overview the
      status of studies dealing with the involvement of integrins in the unique
      aggressive character of PDAC, the current status of experimental cancer therapies
      targeted at integrins, and the possible application of these preliminary clinical
      experiments to future PDAC therapy. I will also try to delineate the reasons for
      the failures of PDAC therapies and make some modest suggestions that might
      improve the health scientific community approaches to this extremely difficult
      problem. 

PMID- 25610999
TI  - Analysis of the developing neural system using an in vitro model by Raman
      spectroscopy.
AB  - We developed an in vitro model of early neural cell development. The maturation
      of a normal neural cell was studied in vitro using Raman spectroscopy for 120
      days. The Raman spectra datasets were analyzed by principal component analysis
      (PCA) to investigate the relationship between maturation stages and molecular
      composition changes in neural cells. According to the PCA, the Raman spectra
      datasets can be classified into four larger groups. Previous electrophysiological
      studies have suggested that a normal neural cell goes through three maturation
      states. The groups we observed by Raman analysis showed good agreement with the
      electrophysiological results, except with the addition of a fourth state. The
      results demonstrated that Raman analysis was powerful to investigate the daily
      changes in molecular composition of the growing neural cell. This in vitro model
      system may be useful for future studies of the effects of endocrine disrupters in
      the developing early neural system. 

PMID- 25611000
TI  - Anesthetic management of emergent laparoscopic bilateral adrenalectomy in a
      patient with a life-threatening cortisol crisis.
AB  - Cushing syndrome may rarely present with life-threatening hypercortisolism,
      manifested by hypertension, hypokalemia, hyperglycemia, and edema. If medical
      treatment proves ineffective in ameliorating the symptoms, emergent rescue
      adrenalectomy may be the only way to relieve the crisis. We describe the
      anesthetic management of a patient with an ectopic adrenocorticotropic hormone
      secreting tumor, whose condition was rapidly deteriorating due to severe cortisol
      excess, and emergent adrenalectomy was the only available therapeutic modality.
      Despite severe metabolic derangement, edema, and incipient respiratory failure,
      emergent bilateral laparoscopic adrenalectomy was performed and the patient
      improved sufficiently to undergo surgery for the ectopic lesion without incident.

PMID- 25611001
TI  - Obstetric anesthesia for harlequin ichthyosis: a unique challenge.
AB  - Harlequin ichthyosis (HI) is a rare disorder of defective lipid transport
      resulting in severe epidermal hyperkeratosis producing large plate-like scales.
      Although mortality is high, improved treatments have allowed some with HI to
      survive into their third and fourth decades. However, until this case, there have
      been no known reports of pregnancy followed by birth of a healthy neonate to a
      mother with HI. We report one of the only approximately 25 known current HI
      survivors worldwide unique in having carried a pregnancy to full term and outline
      challenges for the anesthesiologist during labor and delivery. 

PMID- 25611002
TI  - Acute cellular insulin resistance and hyperglycemia associated with
      hypophosphatemia after cardiac surgery.
AB  - Successful glycemic control reduces morbidity and mortality in cardiac surgery
      patients. Protocols that include insulin infusions are commonly followed to
      achieve target blood glucose levels. Insulin resistance has been reported and
      linked to low serum phosphate levels in animal models and studies in diabetic
      outpatients, but not in postoperative patients. The following case series is a
      retrospective observational review of 8 cardiac surgery patients who developed
      insulin resistance early after surgery; this resistance was reversed by
      correcting serum hypophosphatemia. We discuss the multiple underlying mechanisms
      causing hypophosphatemia. 

PMID- 25611003
TI  - Transient and reproducible loss of motor-evoked potential signals after
      intravenous levetiracetam in a child undergoing craniotomy for resection of
      astrocytoma.
AB  - Transcranial electrical motor-evoked potential (tceMEP) monitoring is used in
      complex intracranial and spinal surgeries to detect and prevent neurological
      injury. We present a case of transient, reproducible loss of tceMEPs after an
      infusion of levetiracetam during craniotomy and tumor resection in a child.
      Cessation of the infusion resulted in restoration of baseline tceMEPs. When the
      infusion was resumed at the end of the procedure, a similar decrease in tceMEPs
      was seen as before, after the infusion was stopped. The surgery and postoperative
      course proceeded without incident, and the patient experienced a full recovery. 

PMID- 25611004
TI  - Rheumatoid arthritis--a neuroendocrine immune disorder: glucocorticoid
      resistance, relative glucocorticoid deficiency, low-dose glucocorticoid therapy,
      and insulin resistance.

PMID- 25611005
TI  - Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71
      associated meningoencephalitis.
AB  - Enterovirus 71 (EV71) infection can cause severe neurological complications
      including meningoencephalitis (ME) in some patients with hand, foot and mouth
      disease (HFMD). However, to date no studies have reported changes in cytokine
      concentrations and their correlations with clinical variables in patients with ME
      following EV71 infection. In this study, responses of Th1/Th2 cytokine, including
      IL-2, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma, in cerebrospinal fluid (CSF)
      from patients with EV71-related HFMD with ME and patients with febrile
      convulsions (FC) were analyzed using cytometric bead array technology. It was
      found that CSF IL-6 and IFN-gamma concentrations were significantly higher in
      patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6
      and IFN-gamma concentrations were correlated with CSF cytology, fever duration
      and duration of hospital stay. More interestingly, a positive correlation between
      CSF IL-6 and IFN-gamma concentrations was observed. Finally, receiver operating
      characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set
      for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for
      discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-gamma may be
      associated with EV71-induced neuropathology.

PMID- 25611006
TI  - Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates:
      linker effects on the relaxivity.
AB  - The relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles
      is the result of the complex interplay between the nanoparticle size, the water
      exchange rate and the chelate structure. In this work we study the effect of the
      length of omega-thioalkyl linkers, anchoring fast water exchanging Gd(3+)
      chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates.
      Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and
      lipoyl amide conjugates of the DO3A-N-(alpha-amino)propionate chelator were
      prepared and studied as potential CA for MRI. High relaxivities per chelate, of
      the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25  degrees C), were attained
      thanks to simultaneous optimization of the rotational correlation time and of the
      water exchange rate. Fast local rotational motions of the immobilized chelates
      around connecting linkers (internal flexibility) still limit the attainable
      relaxivity. The degree of internal flexibility of the immobilized chelates seems
      not to be correlated with the length of the connecting linkers. Biodistribution
      and MRI studies in mice suggest that the in vivo behavior of the gold
      nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm)
      undergo fast renal clearance and avoidance of the RES organs while larger
      nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High
      relaxivities, allied to chelate and nanoparticle stability and fast renal
      clearance in vivo suggest that functionalized gold nanoparticles hold great
      potential for further investigation as MRI contrast agents. This study
      contributes to a better understanding of the effect of linker length on the
      relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a
      relevant contribution towards "design rules" for nanostructures functionalized
      with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging. 

PMID- 25611007
TI  - X-Ray Excited Luminescence Chemical Imaging of Bacterial Growth on Surfaces
      Implanted in Tissue.
AB  - A pH sensor film is developed that can be coated on an implant surface and imaged
      using a combination of X-ray excitation and visible spectroscopy to monitor
      bacterial infection and treatment of implanted medical devices (IMDs) through
      tissue. X-ray scintillators in the pH sensor film generate light when an X-ray
      beam irradiates them. This light first passes through a layer containing pH
      indicator that alters the spectrum according to pH, then passes through and out
      of the tissue where it is detected by a spectrometer. A reference region on the
      film is used to account for spectral distortion from wavelength-dependent
      absorption and scattering in the tissue. pH images are acquired by moving the
      sample relative to the X-ray beam and collecting a spectrum at each location,
      with a spatial resolution limited by the X-ray beam width. Using this X-ray
      excited luminescence chemical imaging (XELCI) to map pH through ex vivo porcine
      tissue, a pH drop is detected during normal bacterial growth on the sensor
      surface, and a restoration of the pH to the bulk value during antibiotic
      treatment over the course of hours with milli-meter resolution. Overall, XELCI
      provides a novel approach to noninvasively image surface pH for studying implant
      infections and treatments. 

PMID- 25611008
TI  - Association between malaria exposure and Kaposi's sarcoma-associated herpes virus
      seropositivity in Uganda.
AB  - OBJECTIVE: Unlike other herpes viruses, Kaposi's sarcoma-associated herpes virus
      (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa.
      The reasons for this are unclear. As part of a wider investigation of factors
      that facilitate transmission in Uganda, a high prevalence country, we examined
      the association between antimalaria antibodies and seropositivity against KSHV.
      METHODS: Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P.
      falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1)
      were measured in samples from 1164 mothers and 1227 children. RESULTS: Kaposi's
      sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15%
      children. Among mothers, KSHV seroprevalence increased with malaria antibody
      titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and
      highest titres for PfMSP-1 and PfAMA-1, respectively (P < 0.0001). Among
      children, only antibodies to PfAMA-1 were significantly associated with KSHV
      seropositivity, (P < 0.0001). In both mothers and children, anti-ORF73 antibodies
      were more strongly associated with malaria antibodies than anti-K8.1 antibodies.
      CONCLUSION: The association between malaria exposure and KSHV seropositivity
      suggests that malaria is a cofactor for KSHV infection or reactivation.

PMID- 25611009
TI  - Osmium-catalyzed tethered aminohydroxylation of glycals: a stereodirected access
      to 2- and 3-aminosugars.
AB  - The osmium-catalyzed aminohydroxylation of glycals has been achieved with
      complete regio- and stereocontrol by taking advantage of the Donohoe tethering
      approach. Glucals and galactals showed complementary reactivity in dependence of
      the stage at which the reaction was performed, i.e., directly or after double
      bond shift consequent to a Ferrier rearrangement (that is, on the 1,2 or 2,3
      unsaturated sugar), allowing access to both classes of 2-amino (mannosamine) and
      3-amino (talosamine) sugar derivatives, respectively. 

PMID- 25611012
TI  - 8-mm versus 10-mm diameter self-expandable metallic stent in bilateral endoscopic
      stent-in-stent deployment for malignant hilar biliary obstruction.
AB  - BACKGROUND: We aimed to clarify the clinical benefits of using 8-mm versus 10-mm
      diameter self-expandable metallic stent (SEMS) in bilateral endoscopic stent-in
      stent (SIS) deployment for malignant hilar biliary obstruction (MHBO). METHODS: A
      total of 72 consecutive patients with MHBO treated by endoscopic bilateral SIS
      deployment were enrolled. The 8-mm and 10-mm diameter SEMSs were used in 37
      patients (8-mm group) and 35 patients (10-mm group), respectively. We
      retrospectively compared technical success, functional success, complications,
      successful re-intervention, time to recurrent biliary obstruction (RBO) and
      survival time between two groups. RESULTS: There were no significant inter-group
      differences in terms of technical success (8-mm vs. 10-mm group, both 100%),
      functional success (96% vs. 100%), early (5% vs. 9%) and late (19% vs. 14%)
      complications other than RBO, and successful endoscopic re-intervention (94% vs.
      100%), respectively. Time to RBO (median: 198 days vs. 222 days; log-rank, P =
      0.440) and survival time (median: 186 days vs. 235 days; log-rank, P = 0.883) did
      not differ significantly between the two groups. However, the success rate of
      endoscopic bilateral revisionary stent insertion for RBO was significantly higher
      in the 10-mm compared to the 8-mm group (68% vs. 31%; P = 0.044). CONCLUSIONS:
      The 10-mm diameter SEMS is more suitable with regard to endoscopic re
      intervention.

PMID- 25611013
TI  - Computational analysis of fluid flow within a device for applying biaxial strain
      to cultured cells.
AB  - In vitro systems for applying mechanical strain to cultured cells are commonly
      used to investigate cellular mechanotransduction pathways in a variety of cell
      types. These systems often apply mechanical forces to a flexible membrane on
      which cells are cultured. A consequence of the motion of the membrane in these
      systems is the generation of flow and the unintended application of shear stress
      to the cells. We recently described a flexible system for applying mechanical
      strain to cultured cells, which uses a linear motor to drive a piston array to
      create biaxial strain within multiwell culture plates. To better understand the
      fluidic stresses generated by this system and other systems of this type, we
      created a computational fluid dynamics model to simulate the flow during the
      mechanical loading cycle. Alterations in the frequency or maximal strain
      magnitude led to a linear increase in the average fluid velocity within the well
      and a nonlinear increase in the shear stress at the culture surface over the
      ranges tested (0.5-2.0 Hz and 1-10% maximal strain). For all cases, the applied
      shear stresses were relatively low and on the order of millipascal with a dynamic
      waveform having a primary and secondary peak in the shear stress over a single
      mechanical strain cycle. These findings should be considered when interpreting
      experimental results using these devices, particularly in the case when the cell
      type used is sensitive to low magnitude, oscillatory shear stresses. 

PMID- 25611014
TI  - Metabolic syndrome: an ill wind that blows some good?
AB  - In this issue of the journal, Brima et al. report thought-provoking research
      providing a potential evolutionary rationale whereby natural selection might have
      preserved genes that predispose to metabolic syndrome. When CD-1 mice were fed a
      high fat diet, this induced metabolic changes characteristic of metabolic
      syndrome. In addition, the high fat diet provided substantial protection from
      lethality due to infection with Trypanosoma cruzi. The authors hypothesize that
      the same genes predispose to both metabolic syndrome and protection against
      infectious disease. Thus, the selective advantage of not dying from infectious
      disease implicitly provides selective pressure predisposing to metabolic
      syndrome. This hypothesis follows a similar line of reasoning that has provided
      explanations for the survival of the HbS mutation for sickle cell disease and
      renal disease-associated genetic variants in apolipoprotein L1. Variants in these
      two genes provide protection from malaria and Trypanosoma brucei rhodesiense,
      respectively.

PMID- 25611016
TI  - Maximal aerobic capacity in the winter-Olympics endurance disciplines: Olympic
      medal benchmarks for the time period 1990-2013.
AB  - PURPOSE: To generate updated Olympic-medal benchmarks for VO2max in winter
      endurance disciplines, examine possible differences in VO2max between medalists
      and nonmedalists, and calculate gender difference in V O2max based on a
      homogeneous subset of world-leading endurance athletes. METHODS: The authors
      identified 111 athletes who participated in winter Olympic Games/World
      Championships in the period 1990 to 2013. All identified athletes tested VO2max
      at the Norwegian Olympic Training Center within +/-1 y of their championship
      performance. Testing procedures were consistent throughout the entire period.
      RESULTS: For medal-winning athletes, the following relative VO2max values
      (mean:95% confidence intervals) for men/women were observed (mL . min-1 . kg-1):
      84:87-81/72:77-68 for cross-country distance skiing, 78:81-75/68:73-64 for cross
      country sprint skiing, 81:84-78/67:73-61 for biathlon, and 77:80-75 for Nordic
      combined (men only). Similar benchmarks for absolute VO2max (L/min) in
      male/female athletes are 6.4:6.1-6.7/4.3:4.1-4.5 for cross-country distance
      skiers, 6.3:5.8-6.8/4.0:3.7-4.3 for cross-country sprint skiers, 6.2:5.7
      6.4/4.0:3.7-4.3 for biathletes, and 5.3:5.0-5.5 for Nordic combined (men only).
      The difference in relative VO2max between medalists and nonmedalists was large
      for Nordic combined, moderate for cross-country distance and biathlon, and
      small/trivial for the other disciplines. Corresponding differences in absolute
      VO2max were small/trivial for all disciplines. Male cross-country medalists
      achieve 15% higher relative VO2max than corresponding women. CONCLUSIONS: This
      study provides updated benchmark VO2max values for Olympic-medal-level
      performance in winter endurance disciplines and can serve as a guideline of the
      requirements for future elite athletes.

PMID- 25611017
TI  - An unusual cause of airway obstruction in a patient in the endoscopy suite.
AB  - A 74-year-old man presented for outpatient endoscopy because of dysphagia and the
      sensation of a mass in the back of his throat. Esophagogastroduodenoscopy
      demonstrated a soft tissue mass in the proximal esophagus that prolapsed into the
      hypopharynx on withdrawal of the endoscope. Complete airway obstruction ensued,
      requiring emergent tracheotomy. The patient was transferred to the hospital for
      further treatment. Surgical resection revealed a rare giant fibrovascular polyp,
      which may be associated with asphyxiation and sudden death. 

PMID- 25611018
TI  - The role of diagnostic ultrasound-guided selective common peroneal nerve block in
      a patient with negative imaging but with classic neuropathic pain after below
      knee amputation.
AB  - Below-knee amputation neuromas may be hard to detect radiographically. This case
      report demonstrates that in a below-knee amputee with negative imaging but with
      classic neuropathic pain, successful diagnostic ultrasound-guided nerve-selective
      peripheral nerve block may be performed to diagnose the problem; subsequent
      resection of the neuroma may relieve severe neuropathic pain. 

PMID- 25611019
TI  - Improving awareness of nonanesthesia-related malignant hyperthermia
      presentations: a tale of two brothers.
AB  - A 30-year-old man developed unexplained rhabdomyolysis, persistently increased
      creatine kinase and severe debilitating muscle cramps. After a nondiagnostic
      neurologic evaluation, he was referred for a muscle biopsy, to include
      histology/histochemistry, a myoglobinuria panel, and a caffeine halothane
      contracture test. Only the caffeine halothane contracture test was positive, and
      a subsequent ryanodine receptor type 1 gene evaluation revealed a mutation
      functionally causative for malignant hyperthermia. His identical twin brother,
      who was suffering from similar complaints, was found to share the same mutation.
      They each require oral dantrolene therapy to control symptoms, despite difficulty
      in identifying health care providers familiar with treating this disorder. 

PMID- 25611020
TI  - Editorial comment: improving awareness of nonanesthesia-related malignant
      hyperthermia presentations: a tale of two brothers.

PMID- 25611022
TI  - Gramicidin conformational changes during riboflavin photosensitized oxidation in
      solution and the effect of N-methylation of tryptophan residues.
AB  - In the present work, we evaluated the role of gramicidin conformation in its
      photosensitized oxidation in organic solvents when irradiated in the presence of
      riboflavin. Gramicidin conformation has been described as monomeric in
      trifluoroethanol and as an intertwined dimer in methanol. Gramicidin showed
      extensive photo-oxidation upon irradiation in the presence of riboflavin in both
      solvents, and tryptophan residues were identified to be involved. We synthesized
      a gramicidin derivative methylated at position 1 of the indole ring of tryptophan
      to assess its effect on gramicidin conformation and photo-oxidation. Methylated
      gramicidin showed very similar absorption and emission spectra to gramicidin, but
      different conformations were identified by circular dichroism spectra. Upon
      irradiation, N-methylated tryptophan residues in the gramicidin derivative were
      not easily photo-oxidized by riboflavin compared to gramicidin. Circular
      dichroism spectra for gramicidin in methanol changed significantly upon
      irradiation in the presence of riboflavin indicating a change in conformation,
      while in trifluoroethanol no such changes were observed. Time-resolved
      fluorescence and anisotropy studies showed that oxidized gramicidin in methanol
      had shorter fluorescence lifetimes and a shorter rotational correlation time
      compared to non-irradiated gramicidin. Additionally, SDS-PAGE analysis showed a
      marked change in the electrophoretic pattern, whereas the high-molecular-weight
      bands disappeared upon irradiation. We interpret all these results in terms of a
      riboflavin photosensitized shift in gramicidin conformation from intertwined to
      monomeric. 

PMID- 25611023
TI  - A limited anodic and cathodic potential window of MoS2: limitations in
      electrochemical applications.
AB  - Molybdenum disulphide has been touted as a good material with diverse possible
      applications such as an energy storage and sensing platform. However, we
      demonstrate here the limitation of MoS2 as an analytical sensing platform due to
      the limited potential window in both the anodic and cathodic regions attributed
      to the inherent electrochemistry (oxidation of Mo(4+) to Mo(6+)) and the
      catalytic hydrogen evolution reaction due to H3O(+) reduction on the MoS2
      surface, respectively. The electrochemical window of MoS2 lies in the region of ~
      0.6 V to +0.7 V (vs. AgCl). We show that such a limited working potential window
      characteristic of MoS2 precludes the detection of important analytes such as
      nitroaromatic explosives, pesticides and mycotoxins which are instead detectable
      on carbon surfaces. The limited potential window of MoS2 has to be taken into
      consideration in the construction of electroanalytical devices based on MoS2. 

PMID- 25611024
TI  - Design and development of a two-dimensional system based on hydrophilic and
      reversed-phase liquid chromatography with on-line sample treatment for the
      simultaneous separation of excreted xenobiotics and endogenous metabolites in
      urine.
AB  - In the present work we describe a two-dimensional liquid chromatographic system
      (2D-LC) with detection by mass spectrometry (MS) for the simultaneous separation
      of endogenous metabolites of clinical interest and excreted xenobiotics deriving
      from exposure to toxic compounds. The 2D-LC system involves two orthogonal
      chromatographic modes, hydrophilic interaction liquid chromatography (HILIC) to
      separate polar endogenous metabolites and reversed-phase (RP) chromatography to
      separate excreted xenobiotics of low and intermediate polarity. Additionally, the
      present proposal has the novelty of incorporating an on-line sample treatment
      based on the use of restricted access materials (RAMs), which permits the direct
      injection of urine samples into the system. The work is focused on the
      instrumental coupling, studying all possible options and attempting to circumvent
      the problems of solvent incompatibility between the RAM device and the two
      chromatographic columns, HILIC and RP. The instrumental configuration developed,
      RAM-HILIC-RPLC-MS/MS, allows the simultaneous assessment of urinary metabolites
      of clinical interest and excreted compounds derived from exposure to toxic agents
      with minimal sample manipulation. Thus, it may be of interest in areas such as
      occupational and environmental toxicology in order to explore the possible
      relationship between the two types of compounds.

PMID- 25611025
TI  - Second and third-generation epidermal growth factor receptor tyrosine kinase
      inhibitors in advanced nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: The first-generation epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, are effective as first
      line treatment of advanced nonsmall cell lung cancer (NSCLC) harboring activating
      EGFR mutations (deletions in exon 19 and exon 21 L858R mutation). EGFR T790 M
      resistance mutation (EGFR T790 M) ultimately emerged in most of these patients.
      The second and third-generation EGFR-TKIs were designed to have more potent
      inhibition of EGFR and to overcome EGFR T790 M. This review describes the recent
      developments of these novel EGFR-TKIs. RECENT FINDINGS: The second-generation
      EGFR-TKIs, afatinib and dacomitinib, irreversibly bind to the tyrosine kinase of
      EGFR and other ErbB-family members. Afatinib has been approved as first-line
      treatment of advanced NSCLC harboring activating EGFR mutations. Dacomitinib is
      under development. Third-generation EGFR-TKIs, AZD9291, CO-1686, and HM61713,
      inhibit both EGFR activating and resistance mutations, while sparing wild-type
      EGFR. In early-phase studies, these drugs demonstrated promising response rates
      against tumors with acquired EGFR T790 M. SUMMARY: Second-generation EGFR-TKI,
      afatinib, is available as first-line treatment of advanced NSCLC harboring
      activating EGFR mutations. Third-generation EGFR-TKIs are under development for
      tumors harboring acquired EGFR T790 M.

PMID- 25611026
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors in early-stage
      nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: Targeted molecular therapy is playing an increasingly
      important role in the treatment of nonsmall cell lung cancer (NSCLC). Epidermal
      growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated
      efficacy in the advanced disease setting. Preliminary findings suggest that EGFR
      TKIs may also be beneficial as adjuvant therapy following complete resection in
      patients with EGFR-mutation-positive early-stage I-III NSCLC; however, many
      questions remain unanswered. RECENT FINDINGS: Single-arm trials of adjuvant EGFR
      TKI therapy in patients with tumors harboring activating EGFR mutations show
      impressive 2-year disease-free survival (DFS). Phase III randomized trial data do
      not support adjuvant EGFR-TKI therapy in unselected completely resected stage I
      III NSCLC, but show improved DFS in patients with completely resected EGFR
      mutated NSCLC. Adverse events leading to treatment withdrawal and dose reductions
      are frequent with adjuvant EGFR-TKI therapy, and relapse following treatment
      withdrawal is common. Adjuvant EGFR-TKIs have not yet been shown to improve the
      overall survival (OS) in patients with tumors harboring activating EGFR
      mutations. SUMMARY: There are no data to support the use of adjuvant EGFR-TKIs in
      unselected early-stage NSCLC. Although EGFR-TKIs hold promise as adjuvant therapy
      in patients whose tumors harbor EGFR mutations, in the absence of definitive data
      confirming an OS benefit eligible patients should continue to receive adjuvant
      chemotherapy following complete resection.

PMID- 25611027
TI  - Use of a Feeding Bundle Appears to Reduce Central Line Utilization in Neonates.
AB  - We investigated whether a standardized feeding bundle reduces central line
      utilization in very low birth weight neonates. A chart review of infants <=1500 g
      requiring a central line was prepared for 2009 to 2012. Infants were stratified
      into 3 weight groups: <=750 g, 751 to 1000 g, and 1001 to 1500 g. The number of
      central line-associated bloodstream infections (CLABSIs) was recorded. Central
      line utilization decreased in all of the groups: 0.45 to 0.28 in <=750 g infants,
      0.4 to 0.27 in 751 to 1000 g infants, and 0.39 to 0.3 in 1001 to 1500 g infants
      (all of the P < 0.001). The CLABSIs rate was unchanged. Implementation of a
      feeding bundle decreased central line utilization. A feeding bundle had no effect
      on the rate of CLABSIs. 

PMID- 25611028
TI  - Nutrient Adequacy and Associated Factors in a Nationwide Sample of German
      Toddlers.
AB  - OBJECTIVES: Nutrition in toddlerhood may have short- and long-term impacts on
      health and nutrition behavior. The objectives of the present article are to
      describe intake of energy and nutrients from the end of infancy to toddlerhood,
      and to examine dietary and socioeconomic factors (socioeconomic status [SES])
      associated with total nutrient adequacy measured by a nutrient-based index
      (Nutrient Quality Index [NQI]). METHODS: In the German Representative Study of
      Toddler Alimentation from 2008, 7-day estimated dietary records were collected
      cross-sectionally from toddlers ages 10 to 36 months (n = 525). The study
      population was recruited in the TNS access panel. The intakes of energy and 18
      nutrients were evaluated and the NQI was determined. Age trends in nutrient
      intake were tested with analysis of variance. Analysis of the association between
      SES and the NQI was performed by multiple linear regression analysis. RESULTS: In
      all of the age groups, energy intake was close to the reference value
      representing moderate physical activity. The mean intake of most vitamins and
      minerals reached the respective reference values, but nutrient density decreased
      with age. Dietary intakes of iron, iodine, and vitamin D are low in our study.
      The NQI reached approximately 80 points and was lower in older children than in
      younger children. NQI was not affected by SES but by formula use. CONCLUSIONS:
      Nutritional quality measured by total nutrient intake is altogether high in
      German toddlers, although NQI decreased with increasing age. The NQI is
      independent of social class. The positive association with formula intake can be
      explained by the general enrichment of vitamins and minerals of these products.

PMID- 25611029
TI  - Impact of Intestinal Rehabilitation Program and Its Innovative Therapies on the
      Outcome of Intestinal Transplant Candidates.
AB  - OBJECTIVES: The outcome of children with intestinal failure has improved during
      the past decade following the introduction of novel therapies by dedicated
      intestinal rehabilitation programs (IRP). The aim of the present study was to
      assess the impact of IRP on the outcome of intestinal transplant (IT) candidates
      and the transplant waiting list. METHODS: A retrospective cohort study of
      children assessed for IT (n = 84) during a 10-year period. Comparisons were made
      among the following 3 time periods: before the establishment of our center's IRP
      (1999-2002; n = 33), early IRP (2003-2005; n = 18), and late IRP (2006-2009; n =
      33). The following endpoints were used: patient outcome following IT assessment
      (not listed, listed and removed from the list, received transplant, died while on
      the list), patient characteristics at IT assessment, and patient status at the
      end of the study. RESULTS: The late-IRP era was associated with an increase in
      patients who were not listed (42% vs 28% at other periods, P = NS) and patients
      who were removed from the IT waiting list because of clinical improvement (P <
      0.0005), and a decrease in those who died before transplant (15% vs >60% at other
      periods, P < 0.0005). The cause of death shifted from traditional causes such as
      liver failure or sepsis to other comorbid conditions (P < 0.005). Improved liver
      function at listing was also observed during late IRP (P < 0.005). CONCLUSIONS:
      Treatment by IRP, coupled with recent advances in the medical management of
      intestinal failure, is associated with improved survival and outcome of patients
      waiting for IT, and may lead to overall reduction in the number of IT in the
      future.

PMID- 25611030
TI  - Clostridium difficile Ileitis in Pediatric Inflammatory Bowel Disease.

PMID- 25611031
TI  - Mucosal inflammation, esophageal eosinophilia, and celiac disease: a little
      "pinch" will have to do you.

PMID- 25611032
TI  - Wilson disease: a matter of copper, but also of zinc.

PMID- 25611033
TI  - Survey of Immunization Practices in Patients With Inflammatory Bowel Disease
      Among Pediatric Gastroenterologists.
AB  - OBJECTIVES: We aimed to determine vaccination practices of pediatric
      gastroenterologists, as well as barriers to following immunization guidelines in
      patients with inflammatory bowel disease. METHODS: Institutions listed in the
      North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
      clinical research registry and/or ImproveCareNow were contacted. A total of 657
      physicians from 129 institutions were asked to complete a 16-question electronic
      survey. RESULTS: A total of 178 physicians (27.1%) responded, of whom 55% were
      male and 83.1% practiced in an academic setting. A total of 11 physicians (6.2%)
      do not routinely assess vaccination status, whereas 63.5% assess at the time of
      diagnosis, 29.8% at "well" visits, and 44.4% before initiating immunosuppression.
      At diagnosis, 51.1% verbally inquire about immunization status, 30.9% obtain
      records, and 9.0% obtain serology.The influenza (78%), hepatitis B (84%), and
      varicella (82%) vaccines were most frequently assessed. Fewer than 55.5% of
      physicians reviewed other vaccines. Physicians using a reminder mechanism were
      more likely to review immunizations at established visits (41.1% vs 20.8%), and
      before transfer to an adult gastroenterologist (14.4% vs 2.6%). Lack of
      coordination of care with primary care practitioners (41%), poor access to
      immunization records (36%), and inability to offer vaccinations in their
      immediate area (55%) are barriers to vaccination. Only 28% believed that primary
      care practitioners were solely responsible for immunizations. CONCLUSIONS: There
      is practice variation among pediatric gastroenterologists in assessment of
      immunizations in patients with inflammatory bowel disease, including the specific
      vaccines assessed, and timing and method of assessment. Inability to coordinate
      care, access immunization records, and offer vaccines through their medical
      practice are barriers to adhering to immunization guidelines.

PMID- 25611034
TI  - Unusual Ulcerations in Crohn Disease.

PMID- 25611035
TI  - Extending supplementary nutrition in malnutrition: more is better?

PMID- 25611036
TI  - GiECAT(KIDS) validated pediatric colonoscopy assessment tool: a call to action.

PMID- 25611037
TI  - Management of ingested foreign bodies in children: a clinical report of the
      NASPGHAN Endoscopy Committee.
AB  - Foreign body ingestions in children are some of the most challenging clinical
      scenarios facing pediatric gastroenterologists. Determining the indications and
      timing for intervention requires assessment of patient size, type of object
      ingested, location, clinical symptoms, time since ingestion, and myriad other
      factors. Often the easiest and least anxiety-producing decision is the one to
      proceed to endoscopic removal, instead of observation alone. Because of
      variability in pediatric patient size, there are less firm guidelines available
      to determine which type of object will safely pass, as opposed to the clearer
      guidelines in the adult population. In addition, the imprecise nature of the
      histories often leaves the clinician to question the timing and nature of the
      ingestion. Furthermore, changes in the types of ingestions encountered,
      specifically button batteries and high-powered magnet ingestions, create an even
      greater potential for severe morbidity and mortality among children. As a result,
      clinical guidelines regarding management of these ingestions in children remain
      varied and sporadic, with little in the way of prospective data to guide their
      development. An expert panel of pediatric endoscopists was convened and produced
      the present article that outlines practical clinical approaches to the pediatric
      patient with a variety of foreign body ingestions. This guideline is intended as
      an educational tool that may help inform pediatric endoscopists in managing
      foreign body ingestions in children. Medical decision making, however, remains a
      complex process requiring integration of clinical data beyond the scope of these
      guidelines. These guidelines should therefore not be considered to be a rule or
      to be establishing a legal standard of care. Caregivers may well choose a course
      of action outside of those represented in these guidelines because of specific
      patient circumstances. Furthermore, additional clinical studies may be necessary
      to clarify aspects based on expert opinion instead of published data. Thus, these
      guidelines may be revised as needed to account for new data, changes in clinical
      practice, or availability of new technology. 

PMID- 25611040
TI  - Iron-catalyzed trifluoromethylation of enamide.
AB  - Herein the first example of the iron(II)-catalyzed trifluoromethylation of
      enamide using mild and simple reaction conditions is reported. The method is cost
      effective and uses the easy-to-handle Togni's reagent as the electrophilic CF3
      source. This transformation is totally regioselective at the C3 position of
      enamides and exhibits broad substrate scope, good functional group tolerance and
      thus demonstrates its useful application in a late-stage fluorination strategy. 

PMID- 25611038
TI  - Characterization of a unique cell population marked by transgene expression in
      the adult cochlea of nestin-CreER(T2)/tdTomato-reporter mice.
AB  - Hair cells in the adult mammalian cochlea cannot spontaneously regenerate after
      damage, resulting in the permanency of hearing loss. Stem cells have been found
      to be present in the cochlea of young rodents; however, there has been little
      evidence for their existence into adulthood. We used nestin-CreER(T2)/tdTomato
      reporter mice to trace the lineage of putative nestin-expressing cells and their
      progeny in the cochleae of adult mice. Nestin, an intermediate filament found in
      neural progenitor cells during early development and adulthood, is regarded as a
      multipotent and neural stem cell marker. Other investigators have reported its
      presence in postnatal and young adult rodents; however, there are discrepancies
      among these reports. Using lineage tracing, we documented a robust population of
      tdTomato-expressing cells and evaluated these cells at a series of adult time
      points. Upon activation of the nestin promoter, tdTomato was observed just below
      and medial to the inner hair cell layer. All cells colocalized with the stem cell
      and cochlear-supporting-cell marker Sox2 as well as the supporting cell and
      Schwann cell marker Sox10; however, they did not colocalize with the Schwann cell
      marker Krox20, spiral ganglion marker NF200, nor glial fibrillary acidic acid
      (GFAP)-expressing supporting cell marker. The cellular identity of this unique
      population of tdTomato-expressing cells in the adult cochlea of nestin
      CreER(T2)/tdTomato mice remains unclear; however, these cells may represent a
      type of supporting cell on the neural aspect of the inner hair cell layer.

PMID- 25611039
TI  - Two-dimensional sum-frequency generation (2D SFG) spectroscopy: summary of
      principles and its application to amyloid fiber monolayers.
AB  - By adding a mid-infrared pulse shaper to a sum-frequency generation (SFG)
      spectrometer, we have built a 2D SFG spectrometer capable of measuring spectra
      analogous to 2D IR spectra but with monolayer sensitivity and SFG selection
      rules. In this paper, we describe the experimental apparatus and provide an
      introduction to 2D SFG spectroscopy to help the reader interpret 2D SFG spectra.
      The main aim of this manuscript is to report 2D SFG spectra of the amyloid
      forming peptide FGAIL. FGAIL is a critical segment of the human islet amyloid
      polypeptide (hIAPP or amylin) that aggregates in people with type 2 diabetes.
      FGAIL is catalyzed into amyloid fibers by many types of surfaces. Here, we study
      the structure of FGAIL upon deposition onto a gold surface covered with a self
      assembled monolayer of methyl-4-mercaptobenzoate (MMB) that produces an ester
      coating. FGAIL deposited on bare gold does not form ordered layers. The measured
      2D SFG spectrum is consistent with amyloid fiber formation, exhibiting both the
      parallel (a+) and perpendicular (a-) symmetry modes associated with amyloid beta
      sheets. Cross peaks are observed between the ester stretches of the coating and
      the FGAIL peptides. Simulations are presented for two possible structures of
      FGAIL amyloid beta-sheets that illustrate the sensitivity of the 2D SFG spectra
      to structure and orientation. These results provide some of the first molecular
      insights into surface catalyzed amyloid fiber structure.

PMID- 25611042
TI  - Cerebral oximetry probes-associated skin burns in pediatric patients.
AB  - Cerebral oxygen monitoring continuously monitors cerebral oxygenation with a
      noninvasive technique based on near-infrared spectroscopy. In this report, we
      describe 2 children in whom skin burns followed the reuse of probes monitoring
      cerebral oxygenation with In Vivo Optical Spectroscopy. 

PMID- 25611041
TI  - High-fidelity artifact correction for cone-beam CT imaging of the brain.
AB  - CT is the frontline imaging modality for diagnosis of acute traumatic brain
      injury (TBI), involving the detection of fresh blood in the brain (contrast of 30
      50 HU, detail size down to 1 mm) in a non-contrast-enhanced exam. A dedicated
      point-of-care imaging system based on cone-beam CT (CBCT) could benefit early
      detection of TBI and improve direction to appropriate therapy. However, flat
      panel detector (FPD) CBCT is challenged by artifacts that degrade contrast
      resolution and limit application in soft-tissue imaging. We present and evaluate
      a fairly comprehensive framework for artifact correction to enable soft-tissue
      brain imaging with FPD CBCT. The framework includes a fast Monte Carlo (MC)-based
      scatter estimation method complemented by corrections for detector lag, veiling
      glare, and beam hardening.The fast MC scatter estimation combines GPU
      acceleration, variance reduction, and simulation with a low number of photon
      histories and reduced number of projection angles (sparse MC) augmented by kernel
      de-noising to yield a runtime of ~4 min per scan. Scatter correction is combined
      with two-pass beam hardening correction. Detector lag correction is based on
      temporal deconvolution of the measured lag response function. The effects of
      detector veiling glare are reduced by deconvolution of the glare response
      function representing the long range tails of the detector point-spread function.
      The performance of the correction framework is quantified in experiments using a
      realistic head phantom on a testbench for FPD CBCT.Uncorrected reconstructions
      were non-diagnostic for soft-tissue imaging tasks in the brain. After processing
      with the artifact correction framework, image uniformity was substantially
      improved, and artifacts were reduced to a level that enabled visualization of ~3
      mm simulated bleeds throughout the brain. Non-uniformity (cupping) was reduced by
      a factor of 5, and contrast of simulated bleeds was improved from ~7 to 49.7 HU,
      in good agreement with the nominal blood contrast of 50 HU. Although noise was
      amplified by the corrections, the contrast-to-noise ratio (CNR) of simulated
      bleeds was improved by nearly a factor of 3.5 (CNR = 0.54 without corrections and
      1.91 after correction). The resulting image quality motivates further development
      and translation of the FPD-CBCT system for imaging of acute TBI. 

PMID- 25611043
TI  - Forehead pulse oximeter-associated pressure injury.
AB  - Peripherally placed transmittance pulse oximeter sensors have been associated
      with patient injury including burns, gangrene, and necrosis. There are 2 reports
      of burn injuries associated with the use of forehead reflectance sensors, but
      there is no report of a pressure injury associated with the use of an OxiMaxTM
      MAX-FASTTM forehead sensor and headband. We report the case of a patient who
      developed tissue necrosis associated with prolonged application of a forehead
      pulse oximeter sensor under a headband and displacement of the sensor cable. 

PMID- 25611044
TI  - Editorial comment: forehead pulse oximeter-associated pressure injury and
      cerebral oximetry probes-associated skin burns in pediatric patients.

PMID- 25611045
TI  - Inadequate spinal anesthesia in a patient with marfan syndrome and dural ectasia.
AB  - Lumbosacral dural ectasia is frequently observed in patients with Marfan
      syndrome. Although neuraxial anesthesia is often used in peripartum anesthetic
      management, few reports describe the effects of dural ectasia on the spread and
      duration of neuraxial anesthesia. We report a case of combined spinal-epidural
      anesthesia for a cesarean delivery in a patient with Marfan syndrome in whom
      complications probably related to dural ectasia occured. 

PMID- 25611046
TI  - Accidental tracheal extubation of a patient in the prone position.
AB  - While undergoing emergency C6-C7 corpectomy and anterior and posterior fusion,
      our prone patient in whom airway management had been difficult experienced
      unplanned tracheal extubation. Herein, we describe emergency airway management
      including reintubation and provide suggestions for airway management in the prone
      positioned patient. 

PMID- 25611048
TI  - Multiple relapses in high-grade osteosarcoma: when to stop aggressive therapy?
AB  - The prognosis after relapse of high-grade osteosarcoma is poor and complete
      resection of all tumors is essential for survival. A 6-year old was diagnosed
      with high-grade osteosarcoma and treated according to the COSS-96 protocol.
      Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and
      every time it was possible to achieve complete surgical remission. Additional
      treatments included chemotherapy and dendritic cell-based cancer immune therapy.
      Since the end of therapy of the 5th relapse, he is alive for 111/2 years. Our
      experience further supports that aggressive surgery can help to achieve long-term
      survival even in patients with multiple osteosarcoma relapses.

PMID- 25611047
TI  - A summary of the osteosarcoma banking efforts: a report from the Children's
      Oncology Group and the QuadW Foundation.
AB  - BACKGROUND: Survival rates of patients with osteosarcoma have remained stagnant
      over the last thirty years. Better understanding of biology, new therapeutics,
      and improved biomarkers are needed. The Children's Oncology Group (COG) addressed
      this need by developing one of the largest osteosarcoma biorepositories ever,
      containing over 15,000 tumor and tissue samples from over 1,500 patients.
      PROCEDURE: The biology study P9851 and the banking study AOST06B1 has enrolled
      1,787 patients (as of September, 2013). Clinical information was lacking on 510
      patients on P9851, who were not enrolled on a concurrent therapeutic trial. The
      value of these specimens was diminished. The lack of statistical support
      available for biology projects slowed the analysis of several critical studies.
      The QuadW Foundation, CureSearch, and the COG formed the Childhood Sarcoma
      Biostatistics and Annotation Office (CSBAO) to provide the infrastructure and
      address these needs by linking clinically annotated patient data to archived
      tissue samples and to develop biostatistical support for childhood sarcoma
      research. RESULTS: Originally 5.3% of samples from the 510 patients on P9851 not
      enrolled on a therapeutic study had full clinical annotation. The efforts of the
      CSBAO have linked clinical annotation to 90.8% of those specimens and provided
      statistical analyses to several studies that had used COG samples. As a result,
      24 biology studies in osteosarcoma have been completed and published in peer
      reviewed journals. CONCLUSIONS: These samples and in-silico data are available to
      the research community for basic and translational science projects to improve
      the biological understanding and treatment of patients affected by osteosarcoma.

PMID- 25611050
TI  - Revealing the preferred interlayer orientations and stackings of two-dimensional
      bilayer gallium selenide crystals.
AB  - Characterizing and controlling the interlayer orientations and stacking orders of
      two-dimensional (2D) bilayer crystals and van der Waals (vdW) heterostructures is
      crucial to optimize their electrical and optoelectronic properties. The four
      polymorphs of layered gallium selenide (GaSe) crystals that result from different
      layer stackings provide an ideal platform to study the stacking configurations in
      2D bilayer crystals. Through a controllable vapor-phase deposition method,
      bilayer GaSe crystals were selectively grown and their two preferred 0 degrees 
      or 60 degrees  interlayer rotations were investigated. The commensurate stacking
      configurations (AA' and AB stacking) in as-grown bilayer GaSe crystals are
      clearly observed at the atomic scale, and the Ga-terminated edge structure was
      identified using scanning transmission electron microscopy. Theoretical analysis
      reveals that the energies of the interlayer coupling are responsible for the
      preferred orientations among the bilayer GaSe crystals. 

PMID- 25611051
TI  - Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk
      stratification and management.
AB  - DISEASE OVERVIEW: Polycythemia vera (PV) and essential thrombocythemia (ET) are
      myeloproliferative neoplasms, respectively characterized by erythrocytosis and
      thrombocytosis. Other disease features include leukocytosis, splenomegaly,
      thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic
      or fibrotic transformation. DIAGNOSIS: PV is defined by a JAK2 mutation, whose
      absence, combined with normal or increased serum erythropoietin level, makes the
      diagnosis unlikely. Differential diagnosis in ET includes reactive
      thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis. Janus
      kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus
      oncogene (MPL) mutations occur in approximately 55%, 25%, and 3% of ET patients,
      respectively. The same molecular markers are also present in prefibrotic
      myelofibrosis, which needs to be morphologically distinguished from ET. Survival
      and leukemic/fibrotic transformation: Median survivals are ~14 years for PV and
      20 years for ET; the corresponding values for younger patients are 24 and 33
      years. Life-expectancy in ET is inferior to the control population. JAK2/CALR
      mutational status does not affect survival in ET. Risk factors for survival in ET
      and PV include advanced age, leukocytosis, and thrombosis. Leukemic
      transformation rates at 20 years are estimated at <10% for PV and 5% for ET;
      fibrotic transformation rates are slightly higher. Thrombosis risk
      stratification: Current risk stratification in PV and ET is designed to estimate
      the likelihood of recurrent thrombosis: high-risk is defined by the presence of
      age >60 years or presence of thrombosis history; low-risk is defined by the
      absence of both of these two risk factors. Recent data consider JAK2V617F and
      cardiovascular risk factors as additional risk factors. Presence of extreme
      thrombocytosis might be associated with acquired von Willebrand syndrome (AvWS)
      and, therefore, risk of bleeding. RISK-ADAPTED THERAPY: The main goal of therapy
      in PV and ET is to prevent thrombohemorrhagic complications. In low risk
      patients, this is accomplished by the use of low-dose aspirin and phlebotomy
      (hematocrit target <45%) in PV. In high risk (for thrombosis) patients, treatment
      with hydroxyurea is additionally recommended. Treatment with busulfan or
      interferon-alpha is usually effective in hydroxyurea failures and the additional
      value of JAK inhibitor therapy in such cases is limited. Screening for AvWS is
      recommended before administrating aspirin, in the presence of extreme
      thrombocytosis.

PMID- 25611052
TI  - Mode of iron(III) chelation by hexadentate hydroxypyridinones.
AB  - Tripodal hexadentate hydroxypyridin-4-ones are increasingly utilised as iron(III)
      and gallium(III) ligands, their attachment to proteins being particularly useful
      for positron emission tomography (PET). A widely studied tripodal ligand
      NTA(BuHP)3, which is reported to form 1:1 iron(III) and gallium(III) complexes in
      aqueous, media forms 2:2 complexes under physiological conditions. This important
      difference has implications for both iron chelation therapy and PET imaging.

PMID- 25611053
TI  - Reduced functional connectivity in the thalamo-insular subnetwork in patients
      with acute anorexia nervosa.
AB  - The neural underpinnings of anorexia nervosa (AN) are poorly understood. Results
      from existing functional brain imaging studies using disorder-relevant food- or
      body-stimuli have been heterogeneous and may be biased due to varying compliance
      or strategies of the participants. In this study, resting state functional
      connectivity imaging was used. To explore the distributed nature and complexity
      of brain function we characterized network patterns in patients with acute AN.
      Thirty-five unmedicated female acute AN patients and 35 closely matched healthy
      female participants underwent resting state functional magnetic resonance
      imaging. We used a network-based statistic (NBS) approach [Zalesky et al., 2010a]
      to identify differences between groups by isolating a network of interconnected
      nodes with a deviant connectivity pattern. Group comparison revealed a subnetwork
      of connections with decreased connectivity including the amygdala, thalamus,
      fusiform gyrus, putamen and the posterior insula as the central hub in the
      patient group. Results were not driven by changes in intranodal or global
      connectivity. No network could be identified where AN patients had increased
      coupling. Given the known involvement of the identified thalamo-insular
      subnetwork in interoception, decreased connectivity in AN patients in these nodes
      might reflect changes in the propagation of sensations that alert the organism to
      urgent homeostatic imbalances and pain-processes that are known to be severely
      disturbed in AN and might explain the striking discrepancy between patient's
      actual and perceived internal body state.

PMID- 25611054
TI  - Ebola virus: melatonin as a readily available treatment option.
AB  - There is currently an urgent need for a viable, cheap, and readily available
      treatment for the Ebola virus outbreak in West Africa. Here, it is proposed that
      melatonin may have significant utility in helping the management of this
      outbreak. Optimizing natural killer (NK) cell responses seems crucial to
      surviving Ebola virus infection. Melatonin increases NK cell cytotoxicity
      significantly, suggesting efficacy in managing the Ebola virus. Under conditions
      of challenge, melatonin increases heme oxygenase-1 (HO-1), which inhibits Ebola
      virus replication. Melatonin also has protective effects in cases of septic
      shock, which, although bacterial, has similar end-point presentations involving
      blood vessel leakage. Melatonin's effects on haemorrhage are mediated primarily
      by a decrease in pro-inflammatory cytokines. By optimizing the appropriate immune
      response, melatonin is likely to afford protection to those at high risk of Ebola
      viral infection, as well as having direct impacts on the course of infection per
      se. Although no direct data pertain to the utility of melatonin in the management
      of the Ebola virus, convergent bodies of data suggest its utility, which is
      reviewed in this article.

PMID- 25611055
TI  - Risk of persistent palatal fistula in patients with cleft palate.
AB  - IMPORTANCE: Many individuals with a cleft palate also have an associated
      craniofacial syndrome or anomaly. OBJECTIVE: To investigate the predictive
      associations of persistent palatal fistulas in patients with previously repaired
      cleft palate. DESIGN, SETTING, AND PARTICIPANTS: We performed a case-control
      study of patients with cleft palate repairs from January 1, 1986, through
      December 31, 2000, at a major tertiary care hospital center in the Bronx, New
      York. The study population consisted of patients who had their primary surgery
      before the age of 3 years and had all their cleft-related treatment completed at
      the same hospital center. Palatal fistula was defined as a breakdown of the
      primary surgical repair of the palate, resulting in persistent patency between
      the oral and nasal cavities. Data collection was conducted by using the hospital
      centers' electronic medical records and patient tracking systems and confirmed by
      review of hard copies of patient records. MAIN OUTCOMES AND MEASURES: The Veau
      classification system was used to classify the preoperative cleft severity.
      RESULTS: A total of 130 patients were identified-23 patients with palatal fistula
      and 107 controls. A total of 12 girls and 11 boys were identified in the palatal
      fistula group and 56 girls and 51 boys in the control group. The mean patient age
      at the time of palatoplasty was 12.6 and 14.5 months in the palatal fistula and
      control groups, respectively. A statistically significant association was found
      between the outcome of fistula and severity of cleft, as defined by the Veau
      classification system (P = .01). Furthermore, for each Veau class increase, the
      odds of a palatal fistula increased by 2.64 (95% CI, 1.35-5.13; P = .004). No
      statistically significant associations were found between the outcome of fistula
      and the following independent variables: patient sex (P = .98), patient age at
      palatoplasty (P = .82), type of palatoplasty (P = .57), surgeon (P = .15),
      orthodontic treatment (P = .59), ear infection (P = .30), or clefts associated
      with syndromes (P = .96). CONCLUSIONS AND  RELEVANCE: Palatal fistulas are
      reliably associated with severity of cleft, as defined by the Veau classification
      system. This knowledge gives the health care professional a more reliable method
      of preoperatively assessing the risk of postoperative palatal fistula in the
      cleft palate population. LEVEL OF EVIDENCE: 3.

PMID- 25611057
TI  - The evolutionary dynamics of timing of maternal immunity: evaluating the role of
      age-specific mortality.
AB  - If a female survives an infection, she can transfer antibodies against that
      particular pathogen to any future offspring she produces. The resulting
      protection of offspring for a period after their birth is termed maternal
      immunity. Because infection in newborns is associated with high mortality, the
      duration of this protection is expected to be under strong selection.
      Evolutionary modelling structured around a trade-off between fertility and
      duration of maternal immunity has indicated selection for longer duration of
      maternal immunity for hosts with longer lifespans. Here, we use a new modelling
      framework to extend this analysis to consider characteristics of pathogens (and
      hosts) in further detail. Importantly, given the challenges in characterizing
      trade-offs linked to immune function empirically, our model makes no assumptions
      about costs of longer lasting maternal immunity. Rather, a key component of this
      analysis is variation in mortality over age. We found that the optimal duration
      of maternal immunity is shaped by the shifting balance of the burden of infection
      between young and old individuals. As age of infection depends on characteristics
      of both the host and the pathogen, both affect the evolution of duration of
      maternal immunity. Our analysis provides additional support for selection for
      longer duration of maternal immunity in long-lived hosts, even in the absence of
      explicit costs linked to duration of maternal immunity. Further, the scope of our
      results provides explanations for exceptions to the general correlation between
      duration of maternal immunity and lifespan, as we found that both pathogen
      characteristics and trans-generational effects can lead to important shifts in
      fitness linked to maternal immunity. Finally, our analysis points to new
      directions for quantifying the trade-offs that drive the development of the
      immune system. 

PMID- 25611058
TI  - Emotion regulation in borderline personality disorder: the role of self
      criticism, shame, and self-compassion: (commentary on Emotional processing in a
      ten-session general psychiatric treatment for Borderline Personality Disorder: a
      case study).

PMID- 25611056
TI  - Binding cavities and druggability of intrinsically disordered proteins.
AB  - To assess the potential of intrinsically disordered proteins (IDPs) as drug
      design targets, we have analyzed the ligand-binding cavities of two datasets of
      IDPs (containing 37 and 16 entries, respectively) and compared their properties
      with those of conventional ordered (folded) proteins. IDPs were predicted to
      possess more binding cavity than ordered proteins at similar length, supporting
      the proposed advantage of IDPs economizing genome and protein resources. The
      cavity number has a wide distribution within each conformation ensemble for IDPs.
      The geometries of the cavities of IDPs differ from the cavities of ordered
      proteins, for example, the cavities of IDPs have larger surface areas and
      volumes, and are more likely to be composed of a single segment. The druggability
      of the cavities was examined, and the average druggable probability is estimated
      to be 9% for IDPs, which is almost twice that for ordered proteins (5%). Some
      IDPs with druggable cavities that are associated with diseases are listed. The
      optimism versus obstacles for drug design for IDPs is also briefly discussed. 

PMID- 25611059
TI  - Specific EEG sleep pattern in the prefrontal cortex in primary insomnia.
AB  - OBJECTIVE: To assess the specific prefrontal activity in comparison to those in
      the other main cortical areas in primary insomnia patients and in good sleepers.
      METHODS: Fourteen primary insomnia patients and 11 good sleepers were included in
      the analysis. Participants completed one night of polysomnography in the sleep
      lab. Power spectra were calculated during the NREM (Non-rapid eyes movements) and
      the REM (Rapid eyes movements) sleep periods at prefrontal, occipital, temporal
      and central electrode positions. RESULTS: During the NREM sleep, the power
      spectra did not differ between groups in the prefrontal cortex; while primary
      insomnia patients exhibited a higher beta power spectrum and a lower delta power
      spectrum compared to good sleepers in other areas. During the REM sleep, the
      beta1 power spectrum was lower in the prefrontal cortex in primary insomnia
      patients compared to good sleepers; while no significant difference between
      groups was obtained for the other areas. CONCLUSIONS: The present study shows a
      specific prefrontal sleep pattern during the whole sleep period. In addition, we
      suggest that primary insomnia patients displayed a dysfunction in the
      reactivation of the limbic system during the REM sleep and we give additional
      arguments in favor of a sleep-protection mechanism displayed by primary insomnia
      patients.

PMID- 25611060
TI  - Effects of hierarchical roost removal on northern long-eared bat (Myotis
      septentrionalis) maternity colonies.
AB  - Forest roosting bats use a variety of ephemeral roosts such as snags and
      declining live trees. Although conservation of summer maternity habitat is
      considered critical for forest-roosting bats, bat response to roost loss still is
      poorly understood. To address this, we monitored 3 northern long-eared bat
      (Myotis septentrionalis) maternity colonies on Fort Knox Military Reservation,
      Kentucky, USA, before and after targeted roost removal during the dormant season
      when bats were hibernating in caves. We used 2 treatments: removal of a single
      highly used (primary) roost and removal of 24% of less used (secondary) roosts,
      and an un-manipulated control. Neither treatment altered the number of roosts
      used by individual bats, but secondary roost removal doubled the distances moved
      between sequentially used roosts. However, overall space use by and location of
      colonies was similar pre- and post-treatment. Patterns of roost use before and
      after removal treatments also were similar but bats maintained closer social
      connections after our treatments. Roost height, diameter at breast height,
      percent canopy openness, and roost species composition were similar pre- and post
      treatment. We detected differences in the distribution of roosts among decay
      stages and crown classes pre- and post-roost removal, but this may have been a
      result of temperature differences between treatment years. Our results suggest
      that loss of a primary roost or <= 20% of secondary roosts in the dormant season
      may not cause northern long-eared bats to abandon roosting areas or substantially
      alter some roosting behaviors in the following active season when tree-roosts are
      used. Critically, tolerance limits to roost loss may be dependent upon local
      forest conditions, and continued research on this topic will be necessary for
      conservation of the northern long-eared bat across its range. 

PMID- 25611062
TI  - Does Decreased c-KIT Expression in Myenteric Interstitial Cells of Cajal Cause
      Decreased Spontaneous Contraction in Murine Proximal Colon?

PMID- 25611061
TI  - Secreted herpes simplex virus-2 glycoprotein G modifies NGF-TrkA signaling to
      attract free nerve endings to the site of infection.
AB  - Herpes simplex virus type 1 (HSV-1) and HSV-2 are highly prevalent viruses that
      cause a variety of diseases, from cold sores to encephalitis. Both viruses
      establish latency in peripheral neurons but the molecular mechanisms facilitating
      the infection of neurons are not fully understood. Using surface plasmon
      resonance and crosslinking assays, we show that glycoprotein G (gG) from HSV-2,
      known to modulate immune mediators (chemokines), also interacts with neurotrophic
      factors, with high affinity. In our experimental model, HSV-2 secreted gG (SgG2)
      increases nerve growth factor (NGF)-dependent axonal growth of sympathetic
      neurons ex vivo, and modifies tropomyosin related kinase (Trk)A-mediated
      signaling. SgG2 alters TrkA recruitment to lipid rafts and decreases TrkA
      internalization. We could show, with microfluidic devices, that SgG2 reduced NGF
      induced TrkA retrograde transport. In vivo, both HSV-2 infection and SgG2
      expression in mouse hindpaw epidermis enhance axonal growth modifying the
      termination zone of the NGF-dependent peptidergic free nerve endings. This
      constitutes, to our knowledge, the discovery of the first viral protein that
      modulates neurotrophins, an activity that may facilitate HSV-2 infection of
      neurons. This dual function of the chemokine-binding protein SgG2 uncovers a
      novel strategy developed by HSV-2 to modulate factors from both the immune and
      nervous systems. 

PMID- 25611063
TI  - Alteration of gut microbiota and efficacy of probiotics in functional
      constipation.

PMID- 25611065
TI  - Proton pump inhibitors reduce the size and acidity of the gastric Acid pocket.

PMID- 25611066
TI  - Alteration of fecal microbiota in patients with postinfectious irritable bowel
      syndrome.

PMID- 25611067
TI  - "Chicago classification" should be challenged in the diagnosis of achalasia:
      heterogeneity of achalasia.

PMID- 25611068
TI  - Thickened internal anal sphincter has been reported to be a typical finding in
      solitary rectal ulcer syndrome.

PMID- 25611064
TI  - Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of
      Colonic Motility and Hyperalgesia.
AB  - The corticotropin-releasing factor (CRF) signaling systems encompass CRF and the
      structurally related peptide urocortin (Ucn) 1, 2, and 3 along with 2 G-protein
      coupled receptors, CRF1 and CRF2. CRF binds with high and moderate affinity to
      CRF1 and CRF2 receptors, respectively while Ucn1 is a high-affinity agonist at
      both receptors, and Ucn2 and Ucn3 are selective CRF2 agonists. The CRF systems
      are expressed in both the brain and the colon at the gene and protein levels.
      Experimental studies established that the activation of CRF1 pathway in the brain
      or the colon recaptures cardinal features of diarrhea predominant irritable bowel
      syndrome (IBS) (stimulation of colonic motility, activation of mast cells and
      serotonin, defecation/watery diarrhea, and visceral hyperalgesia). Conversely,
      selective CRF1 antagonists or CRF1/CRF2 antagonists, abolished or reduced
      exogenous CRF and stress-induced stimulation of colonic motility, defecation,
      diarrhea and colonic mast cell activation and visceral hyperalgesia to colorectal
      distention. By contrast, the CRF2 signaling in the colon dampened the CRF1
      mediated stimulation of colonic motor function and visceral hyperalgesia. These
      data provide a conceptual framework that sustained activation of the CRF1 system
      at central and/or peripheral sites may be one of the underlying basis of IBS
      diarrhea symptoms. While targeting these mechanisms by CRF1 antagonists provided
      a relevant novel therapeutic venue, so far these promising preclinical data have
      not translated into therapeutic use of CRF1 antagonists. Whether the existing or
      newly developed CRF1 antagonists will progress to therapeutic benefits for stress
      sensitive diseases including IBS for a subset of patients is still a work in
      progress.

PMID- 25611069
TI  - Time-varying respiratory system elastance: a physiological model for patients who
      are spontaneously breathing.
AB  - BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific
      mechanical ventilation (MV), but the applications are limited to fully sedated MV
      patients who have little or no spontaneously breathing efforts. This research
      presents a time-varying elastance (E(drs)) model that can be used in
      spontaneously breathing patients to determine their respiratory mechanics.
      METHODS: A time-varying respiratory elastance model is developed with a negative
      elastic component (E(demand)), to describe the driving pressure generated during
      a patient initiated breathing cycle. Data from 22 patients who are partially
      mechanically ventilated using Pressure Support (PS) and Neurally Adjusted
      Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the
      time-varying elastance model and its clinical potential. E(drs) of every
      breathing cycle for each patient at different ventilation modes are presented for
      comparison. RESULTS: At the start of every breathing cycle initiated by patient,
      E(drs) is < 0. This negativity is attributed from the E(demand) due to a positive
      lung volume intake at through negative pressure in the lung compartment. The
      mapping of E(drs) trajectories was able to give unique information to patients'
      breathing variability under different ventilation modes. The area under the curve
      of E(drs) (AUCE(drs)) for most patients is > 25 cmH2Os/l and thus can be used as
      an acute respiratory distress syndrome (ARDS) severity indicator. CONCLUSION: The
      E(drs) model captures unique dynamic respiratory mechanics for spontaneously
      breathing patients with respiratory failure. The model is fully general and is
      applicable to both fully controlled and partially assisted MV modes.

PMID- 25611070
TI  - Controlled rotation and vibration of patterned cell clusters using
      dielectrophoresis.
AB  - The localized motion of cells within a cluster is an important feature of living
      organisms and has been found to play roles in cell signaling, communication, and
      migration, thus affecting processes such as proliferation, transcription, and
      organogenesis. Current approaches for inducing dynamic movement into cells,
      however, focus predominantly on mechanical stimulation of single cells, affect
      cell integrity, and, more importantly, need a complementary mechanism to pattern
      cells. In this article, we demonstrate a new strategy for the mechanical
      stimulation of large cell clusters, taking advantage of dielectrophoresis. This
      strategy is based on the cellular spin resonance mechanism, but it utilizes
      coating agents, such as bovine serum albumin, to create consistent rotation and
      vibration of individual cells. The treatment of cells with coating agents
      intensifies the torque induced on the cells while reducing the friction at the
      cell-cell and cell-substrate interfaces, resulting in the consistent motion of
      the cells. Such localized motion can be modulated by varying the frequency and
      voltage of the applied sinusoidal AC signal and can be achieved in the absence
      and presence of flow. This strategy enables the survival and functioning of
      moving cells within large-scale clusters to be investigated. 

PMID- 25611071
TI  - "Triple-punch" strategy for triple negative breast cancer therapy with minimized
      drug dosage and improved antitumor efficacy.
AB  - Effective therapeutics against triple negative breast cancer (TNBC), which has no
      standard-of-care therapy, needs to be developed urgently. Here we demonstrated a
      strategy of integrating indocyanine green (ICG), paclitaxel (PTX), and survivin
      siRNA into one thermosensitive poly(2-(2-methoxyethoxy)ethyl methacrylate-co
      oligo(ethylene glycol) methacrylate)-co-2-(dimethylamino)ethyl methacrylate-b
      poly(D,L-lactide-co-glycolide) (P (MEO2MA-co-OEGMA-co-DMAEMA)-b-PLGA)
      nanoparticle (NP-IPS) for triple-punch strategy against TNBC. The NP-IPS
      significantly enhanced the stability of ICG. Controlled release of the PTX in
      tumor regions was triggered by the hyperthermia produced by laser irradiated ICG.
      The NP-IPS exhibited remarkable antitumor efficacy (almost complete ablation of
      the tumor xenografts) due to the combinational effects of chemotherapy,
      photothermal therapy, and gene therapy with low drug dose (ICG, 0.32 MUmol/kg;
      PTX, 0.54 MUmol/kg; siRNA, 1.5 mg/kg) and minimal side effects. Taken together,
      our current study demonstrates a nanoplatform for triple-therapy, which reveals a
      promising strategy for TNBC treatment.

PMID- 25611072
TI  - Structural investigation of B-Raf paradox breaker and inducer inhibitors.
AB  - The V600E missense mutation in B-Raf kinase leads to an anomalous regulation of
      the MAPK pathway, uncontrolled cell proliferation, and initiation of
      tumorigenesis. While the ATP-competitive B-Raf inhibitors block the MAPK pathway
      in B-Raf mutant cells, they induce conformational changes to wild-type B-Raf
      kinase domain leading to heterodimerization with C-Raf causing a paradoxical
      hyperactivation of MAPK pathway. A new class of inhibitors (paradox breakers) has
      been developed that inhibit B-Raf(V600E) activity without agonistically affecting
      the MAPK pathway in wild-type B-Raf cells. In this study, we explore the
      structural, conformational, and cellular effects on the B-Raf kinase domain upon
      binding of paradox breakers and inducers. Our results indicate that a subtle
      structural difference between paradox inducers and breakers leads to significant
      conformational differences when complexed with B-Raf. This study provides a novel
      insight into the activation of B-Raf by ATP-competitive inhibitors and can aid in
      the design of more potent and selective inhibitors without agonistic function. 

PMID- 25611073
TI  - Benzothiazoline: versatile hydrogen donor for organocatalytic transfer
      hydrogenation.
AB  - CONSPECTUS: The asymmetric reduction of ketimines is an important method for the
      preparation of amines in optically pure form. Inspired by the biological system
      using NAD(P)H, Hantzsch ester has been extensively employed as a hydrogen donor
      in combination with chiral phosphoric acid for the transfer hydrogenation of
      ketimines to furnish amines with high to excellent enantioselectivities. We
      focused on 2-substituted benzothiazoline as a hydrogen donor in the phosphoric
      acid catalyzed transfer hydrogenation reaction of ketimines for the following
      reasons: (1) benzothiazoline is readily prepared just by mixing 2
      aminobenzenethiol and aldehyde, (2) both reactivity (hydrogen donating ability)
      and enantioselectivity would be controlled by tuning the 2-substituent of
      benzothiazoline, and (3) benzothiazoline can be stored in a refrigerator under
      inert atmosphere without conceivable decomposition. Both the 2-position of
      benzothiazoline and the 3,3'-position of phosphoric acid are tunable in order to
      achieve excellent enantioselectivity. Benzothiazoline proved to be useful
      hydrogen donor in combination with chiral phosphoric acid for the transfer
      hydrogenation reaction of ketimine derivatives to afford the corresponding amines
      with high to excellent enantioselectivities by tuning the 2-substituent of
      benzothiazoline. Ketimines derived from acetophenone, propiophenone, alpha-keto
      ester, trifluoromethyl ketone, and difluoromethyl ketone derivatives proved to be
      suitable substrates. Benzothiazoline could be generated in situ starting from 2
      aminobenzenethiol and aromatic aldehyde in the presence of ketimine and chiral
      phosphoric acid and successfully worked in the sequential transfer hydrogenation
      reaction. The reductive amination of dialkyl ketones also proceeded with high
      enantioselectivities. Use of 2-deuterated benzothiazoline led to the formation of
      alpha-deuterated amines with excellent enantioselectivities. The kinetic isotope
      effect (kH/kC = 3.8) was observed in the competitive reaction between H- and D
      benzothiazoline, which explicitly implies that the cleavage of the C-H (C-D) bond
      is the rate-determining step in the transfer hydrogenation reaction.
      Benzothiazoline yielded products with higher enantioselectivity in the transfer
      hydrogenation reaction of ketimines, particularly ketimines derived from
      propiophenone derivatives, than Hantzsch ester. DFT study elucidated the
      mechanism, as well as the difference in selectivity, between benzothiazoline and
      Hantzsch ester. The chiral phosphoric acid activates ketimines and
      benzothiazoline by means of the Bronsted acidic site (proton) and the Bronsted
      basic site (phosphoryl oxygen), respectively, to accelerate the hydride transfer
      reaction.

PMID- 25611074
TI  - Pair distribution function and density functional theory analyses of hydrogen
      trapping by gamma-MnO2.
AB  - In the presence of "Ag2O" as a promoter, gamma-MnO2 traps dihydrogen in its (2 *
      1) and (1 * 1) tunnels. The course of this reaction was examined by analyzing the
      X-ray diffraction patterns of the HxMnO2/"Ag2O" system (0 <= x < 1) on the basis
      of pair distribution function and density functional theory (DFT) analyses.
      Hydrogen trapping occurs preferentially in the (2 * 1) tunnels of gamma-MnO2,
      which is then followed by that in the (1 * 1) tunnels. Our DFT analysis shows
      that this process is thermodynamically favorable. 

PMID- 25611076
TI  - Novel fluorinated surfactants tentatively identified in firefighters using liquid
      chromatography quadrupole time-of-flight tandem mass spectrometry and a case
      control approach.
AB  - Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of
      per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires
      involving highly flammable liquids. The use of perfluorooctanesulfonic acid
      (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been
      linked to substantial environmental contamination. Recent studies have identified
      a large number of novel and infrequently reported fluorinated surfactants in
      different AFFF formulations. In this study, a strategy based on a case-control
      approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS)
      and advanced statistical methods has been used to extract and identify known and
      unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target
      sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target
      acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid
      (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic
      acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or
      significantly more frequently detected at higher levels in firefighters compared
      to controls. The application of this strategy has allowed for identification of
      previously unreported fluorinated chemicals in a timely and cost-efficient way. 

PMID- 25611075
TI  - Water-soluble Fe(II)-H2O complex with a weak O-H bond transfers a hydrogen atom
      via an observable monomeric Fe(III)-OH.
AB  - Understanding the metal ion properties that favor O-H bond formation versus
      cleavage should facilitate the development of catalysts tailored to promote a
      specific reaction, e.g., C-H activation or H2O oxidation. The first step in H2O
      oxidation involves the endothermic cleavage of a strong O-H bond (BDFE = 122.7
      kcal/mol), promoted by binding the H2O to a metal ion, and by coupling electron
      transfer to proton transfer (PCET). This study focuses on details regarding how a
      metal ion's electronic structure and ligand environment can tune the energetics
      of M(HO-H) bond cleavage. The synthesis and characterization of an Fe(II)-H2O
      complex, 1, that undergoes PCET in H2O to afford a rare example of a monomeric
      Fe(III)-OH, 7, is described. High-spin 7 is also reproducibly generated via the
      addition of H2O to {[Fe(III)(O(Me2)N4(tren))]2-(MU-O)}(2+) (8). The O-H bond BDFE
      of Fe(II)-H2O (1) (68.6 kcal/mol) is calculated using linear fits to its Pourbaix
      diagram and shown to be 54.1 kcal/mol less than that of H2O and 10.9 kcal/mol
      less than that of [Fe(II)(H2O)6](2+). The O-H bond of 1 is noticeably weaker than
      the majority of reported M(n+)(HxO-H) (M = Mn, Fe; n+ = 2+, 3+; x = 0, 1)
      complexes. Consistent with their relative BDFEs, Fe(II)-H2O (1) is found to
      donate a H atom to TEMPO(*), whereas the majority of previously reported M(n+)
      O(H) complexes, including [Mn(III)(S(Me2)N4(tren))(OH)](+) (2), have been shown
      to abstract H atoms from TEMPOH. Factors responsible for the weaker O-H bond of
      1, such as differences in the electron-donating properties of the ligand, metal
      ion Lewis acidity, and electronic structure, are discussed.

PMID- 25611077
TI  - Clinical risk factors and serotonin transporter gene variants associated with
      antidepressant-induced mania.
AB  - INTRODUCTION: Identifying clinical and genetic risk factors associated with
      antidepressant-induced mania (AIM) may improve individualized treatment
      strategies for bipolar depression. METHOD: From 2009 to 2012, bipolar depressed
      patients, confirmed by DSM-IV-TR-structured interview, were screened for AIM. An
      AIM+ case was defined as a manic/hypomanic episode within 60 days of starting or
      changing dose of antidepressant, while an AIM- control was defined as an adequate
      (>= 60 days) exposure to an antidepressant with no associated manic/hypomanic
      episode. 591 subjects (205 AIM+ and 386 AIM-) exposed to an antidepressant and a
      subset of 545 subjects (191 AIM+ and 354 AIM-) treated with a selective serotonin
      reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)
      were used to evaluate the association of AIM with phenotypic clinical risk
      factors previously published. 295 white subjects (113 AIM+ cases, 182 AIM
      controls) were genotyped for 3 SLC6A4 variants: the 5-HTTLPR, single nucleotide
      polymorphism (SNP) rs25531, and the intron 2 variable number of tandem repeats
      (VNTR). Tests of association with AIM were performed for each polymorphism and
      the haplotype. RESULTS: The only clinical risk factors associated with AIM in the
      overall and the SSRI + SNRI analysis was bipolar I subtype. The S allele of 5
      HTTLPR was not significantly associated with AIM; however, a meta-analysis
      combining this sample with 5 prior studies provided marginal evidence of
      association (P = .059). The L-A-10 haplotype was associated with a reduced risk
      of AIM (P = .012). DISCUSSION: Narrowly defined, AIM appears to be at greatest
      risk for bipolar I patients. Our haplotype analysis of SLC6A4 suggests that
      future pharmacogenetic studies should not only focus on the SLC6A4 promotor
      variation but also investigate the role of other variants in the gene.

PMID- 25611078
TI  - Effect of polyelectrolyte electron collection layer counteranion on the
      properties of polymer solar cells.
AB  - Polyviologen (PV) derivatives are known materials used for adjusting the work
      function (WF) of cathodes by reducing the electron injection/collection barrier
      at the cathode interface. To tune and improve device performance, we introduce
      different types of counteranions (CAs), such as bromide, tetrafluoroborate, and
      tetraphenylborate, to a PV derivative. The effective WF of the Al cathode is
      shown to depend on the size of the CA, indicating that a Schottky barrier can be
      modulated by the size of the CA. Through the increased size of the CA from
      bromide to tetraphenylborate, the effective WF of the Al cathode is gradually
      decreased, indicating a decreased Schottky barrier at the cathode interface. In
      addition, the change of the power conversion efficiency (PCE) and the short
      circuit current (Jsc) value show good correlation with the change of the WF of
      the cathode, signifying the typical transition from a Schottky to an Ohmic
      contact. The turn-on electric field of the electron-only device without PV was
      0.21 MV/cm, which is dramatically higher than those of devices with PV-X (0.07
      MV/cm for PV-Br, 0.06 MV/cm for PV-BF4, and 0.05 MV/cm for PV-BPh4) This is also
      coincident with a decrease in the Schottky barrier at the cathode interface. The
      device ITO/PEDOT/P3HT:PCBM/PV/Al, with a thin layer of PV derivative and
      tetraphenylborate CA as the cathode buffer layer, has the highest PCE of 4.02%,
      an open circuit voltage of 0.64 V, a Jsc of 11.6 mA/cm2, and a fill factor of
      53.0%. Our results show that it is possible to improve the performance of polymer
      solar cells by choosing different types of CAs in PV derivatives without
      complicated synthesis and to refine the electron injection/collection barrier
      height at the cathode interface.

PMID- 25611080
TI  - Anthropometric profile of powerlifters: differences as a function of bodyweight
      class and competitive success.
AB  - AIM: This study sought to better understand the relationship between
      anthropometric profile and maximal strength, as assessed in the sport of
      powerlifting as relatively little research has examined how differences in
      anthropometry may contribute to bodyweight-related differences in performance or
      between more and less successful lifters in the same bodyweight class. METHODS:
      To address this aim, 63 male powerlifters from an Argentine National Tournament
      were assessed for 31 anthropometric variables taken using ISAK (International
      Society for the Advancement of Kinanthropometry) protocols. Body fractionation
      (adipose, muscle, bone, residual and skin tissue masses) was determined using the
      validated Kerr & Ross five way fractionation model of body composition that has
      yet to be used with powerlifters. RESULTS: Results indicated that the
      powerlifters showed very elevated values of mesomorphy, muscle girths, muscle
      mass, bone breadths, and all this accompanied by a medium to low stature. Most of
      these characteristics were more pronounced in the heavier divisions. The winners
      had significantly larger proportional muscle mass (53.9 +/- 2.2%), muscle to bone
      mass ratio (5.3 +/- 1) and crural index (1.21 +/- 0.12) than the non-winners.
      CONCLUSION: These comparisons reveal some potential key anthropometric
      determinants of high level powerlifting performance. These results further
      support the view that while powerlifters have unique anthropometric profiles,
      more successful powerlifters typically have higher degrees of muscle mass
      expressed per unit height and/or bone mass but similar segment lengths and
      segment length ratios to their less successful peers.

PMID- 25611079
TI  - Correlates of objectively measured physical activity in 5-6-year-old preschool
      children.
AB  - AIM: The aim of this study was to identify gender specific physical activity
      correlates in Danish preschool children, using a socioecological approach.
      METHODS: This was a cross-sectional study conducted in Odense, Denmark. The
      gender specific models were based on data from 174 boys and 177 girls, 5-6 years
      of age and enrolled in 40 randomly selected preschools. Percentage of total daily
      time spent in moderate and vigorously physical activity (MVPA) was measured using
      ActiGraph accelerometers over 5 preschool days and 2 days off. Thirty-nine
      potential correlates of child MVPA across 5 domains were tested for associations
      with gender specific MVPA. RESULTS: The gender specific models consistently
      identified motor coordination and the parents' perceptions of their child's
      activity preferences during free play to be positively associated with MVPA. Days
      with rain or no preschool attendance were negatively associated with MVPA. For
      boys, rural area and the size of the preschool playground were positively
      associated with MVPA, whereas for girls, it was the age and the relative
      preschool indoor area. CONCLUSION: Individual and overall environmental
      correlates of MVPA were identified. However, most correlates were not or only
      weakly related to MVPA. It is possible that the interaction with peers and
      surrounding adults might contribute the most to preschool child MVPA.

PMID- 25611081
TI  - Smoking, activity level and exercise test outcomes in a young population sample
      without cardiopulmonary disease.
AB  - AIM: Whether reduced activity level and exercise intolerance precede the clinical
      diagnosis of cardiopulmonary disorders in smokers is not known. We examined
      activity level and exercise test outcomes in a young population-based sample
      without overt cardiopulmonary disease, differentiating by smoking history.
      METHODS: This was a multiyear cross-sectional study using United States National
      Health and Nutrition Examination Survey data from 1999-2004. Self-reported
      activity level and incremental exercise treadmill testing were obtained on survey
      participants ages 20-49 years, excluding individuals with cardio-pulmonary
      disease. RESULTS: Three thousand seven hundred and one individuals completed
      exercise testing. Compared to never smokers, current smokers with >10 pack years
      reported significantly higher odds of little or no recreation, sport, or physical
      activity (adjusted OR 1.62; 95% CI 1.12-2.35). Mean perceived exertion ratings
      (Borg 6-20) at an estimated standardized workload were significantly greater
      among current smokers (18.3-18.6) compared to never (17.3) and former smokers
      (17.9) (p<0.05). There were no significant differences in the proportions of
      individuals across estimated peak oxygen uptake categories among the groups after
      adjusting for age and sex. Among former smokers, increasing duration of smoking
      abstinence was associated with significantly lower likelihood of low estimated
      peak oxygen uptake categorization (p<0.05). CONCLUSIONS: Among young individuals
      without overt cardiopulmonary disease, current smokers had reduced daily activity
      and higher perceived exertion ratings. Besides supporting early smoking
      cessation, these results set the stage for future studies that examine mechanisms
      of activity restriction in young smokers and the utility of measures of activity
      restriction in the earlier diagnosis of smoking-related diseases.

PMID- 25611082
TI  - Intermittent exercises reduce the hypertension syndromes and improve the quality
      of life.
AB  - BACKGROUND: Hypertension is one of the most common causes for cardiovascular
      mortality in China and physical exercises have been well recognized for its
      prevention and treatment. Recent studies indicated that the methods of exercise
      differed in improving cardiorespiratory fitness, endothelial function, etc.
      METHODS: In the present study, we compared the effects of high-intensity
      intermittent exercise and moderate-intensity continuous exercise on the blood
      pressure, plasma CRAMP level and living quality of hypertensive patients. We
      measured the basic characteristics of all the individuals and made
      intermittent/continuous exercise plans according to each of their conditions.
      RESULTS: The whole training lasted for 16 weeks and the CRAMP level of each
      patient was recorded by blood sampling and ELISA test. The patients' quality of
      life (QoL) was also surveyed to determine their physical and psychological
      health. Our result suggested that the intermittent exercise significantly reduced
      the blood pressure and the CRAMP level of the hypertensive patients. Although the
      physical pain and social function were not improved by either exercises training,
      the other six dimensions of QoL, including physical function, physical role,
      general health condition, vitality, emotional role and mental health, were
      significant improved by exercises, especially by intermittent exercises.
      CONCLUSIONS: To sum up, the high-intensity intermittent exercise and moderate
      intensity continuous exercise could both improve the living quality of
      hypertensive patients, but the effect of intermittent exercise was more obvious
      that it reduced the blood pressure and the CRAMP level of hypertensive patients
      and improve the living quality in a higher level.

PMID- 25611083
TI  - Task complexity reveals expertise of table tennis players.
AB  - BACKGROUND: The purpose of this study was to examine the effect of intensive
      practice in table tennis on perceptual, decision-making and motor-systems. Groups
      of elite (HL, N.=11), intermediate (LL, N.=6) and control players (CC, N.=11)
      performed tasks of different levels. METHODS: All subjects underwent to reaction
      time test and response time test consisting of a pointing task to targets placed
      at distinct distances (15 and 25 cm away) on the right and left sides. Only the
      HL and LL groups were requested to perform the ball speed test in forehand and
      backhand condition. RESULTS: In the CC group reaction time was higher compared to
      the HL (P<0.05) group. In the response time test, there was a significant main
      effect of distance (P<0.0001) and the tennis table expertise (P=0.011). In the
      ball speed test HL players were consistently faster compared to LL players in
      both forehand stroke (P<0.0001) and backhand stroke (P<0.0001). Overall, the
      forehand stroke was significantly faster than the backhand stroke. CONCLUSIONS:
      We can conclude that table tennis players have shorter response times than non
      athletes and the tasks of reaction time and response time are incapable to
      distinguish between the performance of well-trained table tennis players and that
      of intermediate players, but the ball speed test seems to be able to do it.

PMID- 25611084
TI  - Improvements in patient-reported outcomes in patients with psoriasis receiving
      etanercept plus topical therapies: results from REFINE.
AB  - BACKGROUND: The REFINE study examined the efficacy and safety of adding topical
      corticosteroid therapy to etanercept when stepping down from the initial dose of
      etanercept to the maintenance dose. Clinical responses were shown to be similar
      in patients who remained on etanercept 50 mg twice weekly (BIW) and those who
      received etanercept 50 mg once weekly (QW) plus topical therapies through week
      24. OBJECTIVE: The purpose of this analysis was to evaluate the effect of
      treatment on health-related quality of life (HRQoL) for patients in REFINE.
      METHODS: All patients received etanercept 50 mg BIW for 12 weeks and were then
      randomized to etanercept 50 mg BIW or etanercept 50 mg QW plus topical
      corticosteroid as required to clear through week 24. HRQoL measures included the
      Dermatology Life Quality Index (DLQI), Treatment Satisfaction Questionnaire for
      Medication (TSQM) and the Economic Implications of Psoriasis Patient
      Questionnaire. No comparative testing was performed for this descriptive
      analysis. Missing data were imputed using the last observation carried forward.
      RESULTS: For 287 randomized patients (144 etanercept; 143 etanercept plus
      topical), the mean change [standard deviation (SD)] in DLQI from baseline to week
      24 was 10.7 (7.8) for etanercept and 9.9 (6.9) for etanercept plus topical. Mean
      change (SD) in TSQM effectiveness, convenience, side-effects and global
      satisfaction was 27.1 (36.1), 14.8 (25.9), -0.7 (22.0) and 26.7 (32.5) for the
      etanercept arm and 32.5 (40.3), 18.5 (29.0), 1.3 (19.4) and 28.4 (35.9) for
      etanercept plus topical. Economic implications, including healthcare visits,
      employment status, work productivity, ability to perform daily activities and out
      of-pocket expenses were similar between treatment arms. CONCLUSION: At week 24 of
      REFINE, measures of HRQoL were numerically similar in patients who stayed on
      etanercept 50 mg BIW and patients who received etanercept 50 mg QW plus topical
      therapies.

PMID- 25611085
TI  - Reproductive Life Planning: A Concept Analysis.
AB  - BACKGROUND: In 2006, the U.S. Centers for Disease Control and Prevention issued
      10 recommendations on preconception care, which included the statement that
      reproductive life planning should be considered an individual's responsibility
      across his or her life span. PURPOSE: The purpose of this article is to provide a
      concept analysis of reproductive life planning using Walker and Avant's method as
      an organizing framework. METHODS: Search engines were employed to review the
      existing knowledge base of the concept of reproductive life planning. FINDINGS:
      The findings suggest that reproductive life planning is integral to preconception
      care and family planning. Attributes, antecedents, and consequences associated
      with reproductive life planning are discussed. Model, borderline, and contrary
      cases are also provided to illustrate the concept. PRACTICE IMPLICATIONS: A
      reproductive life plan can serve as a framework for promoting reproductive health
      across the life span of both men and women. Healthcare providers must assess the
      individual's ability to understand and utilize educational resources to ensure
      full and effective participation in reproductive life planning.

PMID- 25611086
TI  - Ginkgetin inhibits the growth of DU-145 prostate cancer cells through inhibition
      of signal transducer and activator of transcription 3 activity.
AB  - Signal transducer and activator of transcription 3 (STAT3) is constitutively
      activated in human cancers. Therefore, STAT3 is a therapeutic target of cancer
      drug discovery. We previously reported that natural products inhibited
      constitutively activated STAT3 in human prostate tumor cells. We used a dual
      luciferase assay to screen 200 natural products isolated from herbal medicines
      and we identified ginkgetin obtained from the leaves of Ginkgo biloba L. as a
      STAT3 inhibitor. Ginkgetin inhibited both inducible and constitutively activated
      STAT3 and blocked the nuclear translocation of p-STAT3 in DU-145 prostate cancer
      cells. Furthermore, ginkgetin selectively inhibited the growth of prostate tumor
      cells stimulated with activated STAT3. Ginkgetin induced STAT3 dephosphorylation
      at Try705 and inhibited its localization to the nucleus, leading to the
      inhibition of expression of STAT3 target genes such as cell survival-related
      genes (cyclin D1 and survivin) and anti-apoptotic proteins (Bcl-2 and Bcl-xL).
      Therefore, ginkgetin inhibited the growth of STAT3-activated tumor cells. We also
      found that ginkgetin inhibited tumor growth in xenografted nude mice and
      downregulated p-STAT3(Tyr705) and survivin in tumor tissues. This is the first
      report that ginkgetin exerts antitumor activity by inhibiting STAT3. Therefore,
      ginkgetin is a good STAT3 inhibitor and may be a useful lead molecule for
      development of a therapeutic STAT3 inhibitor. 

PMID- 25611087
TI  - The biosynthesis and wall-binding of hemicelluloses in cellulose-deficient maize
      cells: an example of metabolic plasticity.
AB  - Cell-suspension cultures (Zea mays L., Black Mexican sweet corn) habituated to
      2,6-dichlorobenzonitrile (DCB) survive with reduced cellulose owing to
      hemicellulose network modification. We aimed to define the hemicellulose
      metabolism modifications in DCB-habituated maize cells showing a mild reduction
      in cellulose at different stages in the culture cycle. Using pulse-chase
      radiolabeling, we fed habituated and non-habituated cultures with
      [(3)H]arabinose, and traced the distribution of (3)H-pentose residues between
      xylans, xyloglucans and other polymers in several cellular compartments for 5 h.
      Habituated cells were slower taking up exogenous [(3)H]arabinose. Tritium was
      incorporated into polysaccharide-bound arabinose and xylose residues, but
      habituated cells diverted a higher proportion of their new [(3)H]xylose residues
      into (hetero) xylans at the expense of xyloglucan synthesis. During logarithmic
      growth, habituated cells showed slower vesicular trafficking of polymers,
      especially xylans. Moreover, habituated cells showed a decrease in the strong
      wall-binding of all pentose-containing polysaccharides studied; correspondingly,
      especially in log-phase cultures, habituation increased the proportion of (3)H
      hemicelluloses ([(3)H]xylans and [(3)H]xyloglucan) sloughed into the medium.
      These findings could be related to the cell walls' cellulose-deficiency, and
      consequent reduction in binding sites for hemicelluloses; the data could also
      reflect the habituated cells' reduced capacity to integrate arabinoxylans by
      extra-protoplasmic phenolic cross-linking, as well as xyloglucans, during wall
      assembly.

PMID- 25611088
TI  - Not just little adults: a review of 102 paediatric ethics consultations.
AB  - AIM: The American Academy of Pediatrics statement on institutional ethics
      committees highlights the importance of paediatric ethics consultation. However,
      little has been published on actual experience with ethics consultation in
      paediatrics. The objective of this study was to review and describe topics
      covered by a large retrospective sample of clinical ethics consultations in
      paediatric medicine. METHODS: We reviewed ethics consultations involving patients
      of <18 years of age from January 2005 to July 2013 at one institution.
      Descriptive statistics of the patient population, the reason for the ethics
      consultation and the consultant's perceived contribution to the case were
      generated. Subgroups of patients were compared based on demographic and clinical
      characteristics using Wilcoxon's rank sum tests, chi-square tests and logistic
      regression models. RESULTS: Most of the 102 eligible consultations originated
      from intensive care units and were requested by attending physicians. The most
      frequent topic leading to consultation was end-of-life issues. Both younger age
      and male sex were associated with consults for end-of-life issues (p < 0.001 and
      p = 0.010). CONCLUSION: This analysis provides important information describing
      the type of consults requested in paediatric medicine, which is necessary given
      the movement towards professionalising clinical ethics consultation. Further
      empirical research is needed on ethics consultation in paediatrics.

PMID- 25611089
TI  - Concentration of fish serum albumin (FSA) in the aqueous extract of Indonesian
      Perciformes fishes' muscle tissue.
AB  - Fish serum albumin (FSA) is an aquatic resource that has potential to be
      developed as nutraceutical. Therefore, research was undertaken to assess albumin
      levels in the aqueous extract of muscle tissue of several Perciformes commonly
      available at a local fish market in Indonesia. Three random replicates for each
      of 17 Perciformes species were collected and assessed for their FSA content by
      application of a reversed-phase (C4) HPLC analytical method. Results of these
      analyses showed that the albumin concentration of the extracts was in the range
      3.49-12.61 g/L, and that they varied significantly (P < 0.05) between species and
      families. This finding may mean that FSA levels are species and family dependent,
      something that could be investigated in future studies. As fishes from the family
      Scrombidae showed the highest concentration (12.61 g/L) of FSA, they would likely
      have the most value as a source for production of albumin-based nutritional
      and/or clinical products.

PMID- 25611090
TI  - Functions and development of red pulp macrophages.
AB  - Macrophages are extremely heterogeneous mononuclear phagocytes widely distributed
      throughout the body. They play unique roles in each organ where they reside.
      Among macrophage subsets, red pulp macrophages (RPMs) that localize in the
      splenic red pulp, are critical for maintenance of blood homeostasis by actively
      phagocytosing injured and senescent erythrocytes and blood-borne particulates.
      Recent evidence indicates that RPMs are mainly generated during embryogenesis and
      are maintained during adult life. Furthermore, the cell-intrinsic and -extrinsic
      factors (namely, Spi-C, IRF8/4, heme oxygenase-1, and M-CSF) that regulate the
      development and survival of RPMs have been identified. Although the immunological
      properties of RPMs have yet to be elucidated fully, pioneering studies have
      demonstrated that these cells are capable of inducing differentiation of
      regulatory T cells via expression of transforming growth factor-beta and secrete
      a large amount of type I interferons during parasitic infections. In this review,
      we describe recent advances in understanding of the functions and development of
      RPMs. 

PMID- 25611092
TI  - Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD
      Peptide?
AB  - As part of a program targeted at developing a resorbable valved tube for
      replacement of the right ventricular outflow tract, we compared three biopolymers
      (polyurethane [PU], polyhydroxyalkanoate (the poly(3-hydroxybutyrate-co-3
      hydroxyvalerate-co-4-hydroxyvalerate) [PHBVV]), and polydioxanone [PDO]) and two
      biofunctionalization techniques (using adipose-derived stem cells [ADSCs] or the
      arginine-glycine-aspartate [RGD] peptide) in a rat model of partial inferior vena
      cava (IVC) replacement. Fifty-three Wistar rats first underwent partial
      replacement of the IVC with an acellular electrospun PDO, PU, or PHBVV patch, and
      31 nude rats subsequently underwent the same procedure using a PDO patch
      biofunctionalized either by ADSC or RGD. Results were assessed both in vitro
      (proliferation and survival of ADSC seeded onto the different materials) and in
      vivo by magnetic resonance imaging (MRI), histology, immunohistochemistry
      [against markers of vascular cells (von Willebrand factor [vWF], smooth muscle
      actin [SMA]), and macrophages ([ED1 and ED2] immunostaining)], and enzyme-linked
      immunosorbent assay (ELISA; for the expression of various cytokines and inducible
      NO synthase). PDO showed the best in vitro properties. Six weeks after
      implantation, MRI did not detect significant luminal changes in any group. All
      biopolymers were evenly lined by vWF-positive cells, but only PDO and PHBVV
      showed a continuous layer of SMA-positive cells at 3 months. PU patches resulted
      in a marked granulomatous inflammatory reaction. The ADSC and RGD
      biofunctionalization yielded similar outcomes. These data confirm the good
      biocompatibility of PDO and support the concept that appropriately peptide
      functionalized polymers may be successfully substituted for cell-loaded
      materials. 

PMID- 25611094
TI  - In reply.

PMID- 25611095
TI  - MYB is a helpful diagnostic marker for adenoid cystic carcinoma in fine-needle
      aspiration biopsy.

PMID- 25611096
TI  - Organizing disparate, seemingly chaotic data into a meaningful and useful order.

PMID- 25611097
TI  - Documenting the cancer journey.

PMID- 25611098
TI  - Pathologists and medical error disclosure: don't wait for an invitation.

PMID- 25611099
TI  - Ordo ab Chao: framework for an integrated disease report.
AB  - CONTEXT: The volume of information that must be assimilated to appropriately
      manage patients with complex or chronic disease can make this task difficult
      because of the number of data points, their variable temporal availability, and
      the fact that they may reside in different systems or even institutions.
      OBJECTIVE .- To outline a framework for building an integrated disease report
      (IDR) that takes advantage of the capabilities of electronic reporting to create
      a single, succinct, interpretative report comprising all disease pertinent data.
      DESIGN: Disease pertinent data of an IDR include pathology results, laboratory
      and radiology data, pathologic correlations, risk profiles, and therapeutic
      implications. We used cancer herein as a representative process for proposing
      what is, to our knowledge, the first example of standardized guidelines for such
      a report. The IDR was defined as a modular, dynamic, electronic summary of the
      most current state of a patient in regard to a particular illness such as lung
      cancer or diabetes, which includes all information relevant for patient
      management. RESULTS: We propose the following 11 core data concepts that an IDR
      should include: patient identification; patient demographics; disease, diagnosis,
      and prognosis; tumor board dispositions and decisions; graphic timeline;
      preresection workup and therapy; resection workup; interpretative comment
      summarizing pertinent findings; biobanking data; postresection workup; and
      disease and patient status at follow-up. CONCLUSIONS: A well-executed IDR should
      improve patient care and efficiency for health care team members. It would
      demonstrate the added value of pathology interpretation and likely contribute to
      a reduction in errors and improved patient safety by decreasing the risk that
      important data will be overlooked.

PMID- 25611100
TI  - Turnaround time for large or complex specimens in surgical pathology: a College
      of American Pathologists Q-Probes study of 56 institutions.
AB  - CONTEXT: Turnaround time (TAT) for large or complex surgical pathology specimens
      is an indicator of efficiency in anatomic pathology and may affect coordination
      of patient care. OBJECTIVE: To establish benchmarks for TAT and to identify
      practice characteristics that may influence TAT. DESIGN: Participants in a 2012 Q
      Probes quality improvement program of the College of American Pathologists
      retrospectively reviewed all surgical pathology cases from the prior 6 months to
      identify up to 50 cases coded as Current Procedural Terminology (CPT) code 88307
      (excluding biopsies) or 88309. Participants reported the times and dates of
      accessioning and final sign-out. RESULTS: A total of 56 institutions reported on
      2763 large or complex cases, which included 70% with CPT code 88307 and 30% with
      CPT code 88309. Cases requiring special handling comprised 51.5%, and 48.5% were
      routine. Among all institutions the median TAT was 2.72 calendar days (10th-90th
      percentile range, 6.23-1.22 days). Longer TAT occurred in governmental
      institutions (median, 6.06 versus 2.13 days; P < .001) and in institutions that
      mandate overnight fixation for some specimen types (median, 3.83 versus 2.07
      days; P = .03). Longer TAT was associated with CPT code 88309 (median, 3.99
      versus 2.82 days; P < .001), special handling (median, 4.13 versus 1.94 days; P <
      .001), frozen section (median, 3.38 versus 2.92 days; P < .001), radical cancer
      resection (P < .001), and malignant cases (P < .001). Turnaround time was not
      significantly affected by either pathology training programs or routine weekend
      sign-out. CONCLUSIONS: This study provides benchmark data for TAT in large or
      complex surgical pathology specimens. Turnaround time was good overall, but the
      range among participating institutions was wide.

PMID- 25611101
TI  - Do liquid-based preparations of pulmonary bronchial brushing specimens perform
      differently from classically prepared cases for the diagnosis of malignancies?
      Observations from the College of American Pathologists interlaboratory comparison
      program in nongynecologic cytology.
AB  - CONTEXT: Pulmonary bronchial brushing specimens can be processed by liquid-based
      or conventional methods. The ability to accurately diagnose a pulmonary
      malignancy with a liquid-based preparation (LBP) versus a conventional
      preparation may differ. OBJECTIVE: To compare the performance of LBPs of
      malignant pulmonary bronchial brushing specimens with the performance of
      conventional preparations. DESIGN: Participant responses from 553 malignant
      pulmonary bronchial brushing samples were evaluated for concordance with the
      general diagnosis. The performance of LBPs was compared with that of classic
      preparations. A nonlinear mixed model was used to analyze the performance by
      reference diagnosis, preparation type, program years, participant type, and the
      interaction terms between these 4 factors. RESULTS: Concordance with the general
      category of malignant disease was observed in 95.2% of conventional Papanicolaou
      stained, 90.9% of modified Giemsa-stained, and 96.9% of LBP (P < .001) samples.
      The results were significantly different between individual reference diagnoses
      (P < .001). The performance of LBPs was consistently higher for most diagnoses
      and was significantly better for squamous cell carcinoma (P = .005), small cell
      carcinoma (P < .001), and metastatic carcinoma not otherwise specified (P <
      .001). All participant types performed significantly better with LBPs of small
      cell carcinoma. Pathologists and cytotechnologists performed significantly better
      with LBPs of squamous cell carcinoma. A significantly higher concordance was
      observed between the general diagnosis and program years 2007-2011 versus 2001
      2006 (P = .006). CONCLUSIONS: Liquid-based preparations performed better than
      conventional methods, with significantly higher performance in squamous cell,
      small cell, and metastatic carcinomas. Improved performance over time may reflect
      more frequent use of LBP methods and increased familiarity with interpreting the
      morphologic findings.

PMID- 25611102
TI  - Clinical validation of targeted next-generation sequencing for inherited
      disorders.
AB  - CONTEXT: Although next-generation sequencing (NGS) can revolutionize molecular
      diagnostics, several hurdles remain in the implementation of this technology in
      clinical laboratories. OBJECTIVES: To validate and implement an NGS panel for
      genetic diagnosis of more than 100 inherited diseases, such as neurologic
      conditions, congenital hearing loss and eye disorders, developmental disorders,
      nonmalignant diseases treated by hematopoietic cell transplantation, familial
      cancers, connective tissue disorders, metabolic disorders, disorders of sexual
      development, and cardiac disorders. The diagnostic gene panels ranged from 1 to
      54 genes with most of panels containing 10 genes or fewer. DESIGN: We used a
      liquid hybridization-based, target-enrichment strategy to enrich 10 067 exons in
      568 genes, followed by NGS with a HiSeq 2000 sequencing system (Illumina, San
      Diego, California). RESULTS: We successfully sequenced 97.6% (9825 of 10 067) of
      the targeted exons to obtain a minimum coverage of 20* at all bases. We
      demonstrated 100% concordance in detecting 19 pathogenic single-nucleotide
      variations and 11 pathogenic insertion-deletion mutations ranging in size from 1
      to 18 base pairs across 18 samples that were previously characterized by Sanger
      sequencing. Using 4 pairs of blinded, duplicate samples, we demonstrated a high
      degree of concordance (>99%) among the blinded, duplicate pairs. CONCLUSIONS: We
      have successfully demonstrated the feasibility of using the NGS platform to
      multiplex genetic tests for several rare diseases and the use of cloud computing
      for bioinformatics analysis as a relatively low-cost solution for implementing
      NGS in clinical laboratories.

PMID- 25611103
TI  - Challenges posed to pathologists in the detection of KRAS mutations in colorectal
      cancers.
AB  - CONTEXT: Detection of KRAS mutation is mandatory to predict response to anti
      epidermal growth factor receptor monoclonal antibodies in patients with
      metastatic colorectal cancers. OBJECTIVE: To demonstrate challenges posed to
      pathologists in the clinical detection of KRAS mutations in colorectal cancers.
      DESIGN: In this retrospective analysis for quality assessment of the
      pyrosequencing assay, we survey the characteristics of 463 formalin-fixed,
      paraffin-embedded neoplastic tissues submitted for KRAS mutation detection during
      a 26-month period. RESULTS: The KRAS mutation was detected in 39.2% of tumors.
      This included 2 tumors with complex pyrograms (GGT>GAG at codon 12 and GGC>GTT at
      codon 13, as resolved by a Pyromaker software program) and 3 tumors with an
      indeterminate percentage of mutant alleles (defined as 4% to 5% and confirmed by
      a next-generation sequencing platform). Among the 25 specimens (5.5%) with fewer
      than 20% tumor cells, 22 were resected after chemotherapy/radiation. Significant
      depletion of tumor cells was observed in rectal cancers resected after
      neoadjuvant therapy (31.0%) versus those without previous treatment (0%) (P =
      .01). We also explore other specimens with low tumor cellularity and potential
      causes of discrepancy between the estimated tumor cell percentage and detected
      mutant allele frequency, such as intratumor heterogeneity of KRAS mutation.
      CONCLUSIONS: Neoadjuvant therapy may deplete tumor cells and confound the
      molecular diagnosis of KRAS mutations. Accurate detection of specimens with poor
      tumor cellularity requires the appropriate selection of neoplastic tissues,
      evaluation of tumor cellularity, use of assays with high sensitivity, and
      prospective quality assessment.

PMID- 25611104
TI  - Clinical performance of hybrid capture 2 human papillomavirus testing for
      recurrent high-grade cervical/vaginal intraepithelial neoplasm in patients with
      an ASC-US Papanicolaou test result during long-term posttherapy follow-up
      monitoring.
AB  - CONTEXT: Women who have been treated for high-grade cervical or vaginal
      intraepithelial neoplasia (CIN or VAIN) or invasive carcinoma are at risk for
      recurrent/persistent disease and require long-term monitoring. The role of human
      papillomavirus (HPV) testing in this setting is unclear. OBJECTIVE: To evaluate
      the clinical performance of the Hybrid Capture 2 (HC2) HPV test for
      recurrent/residual high-grade CIN or VAIN in patients with a posttherapy abnormal
      squamous cells of undetermined significance (ASC-US) Papanicolaou test result.
      DESIGN: We reviewed the follow-up data on 100 patients who had an ASC-US
      Papanicolaou test and HC2 HPV results after treatment for high-grade CIN/VAIN or
      carcinoma. Human papillomavirus genotyping was performed for women with a
      negative HC2 result whose follow-up biopsy revealed CIN/VAIN 2+. RESULTS: The
      patients' mean age was 47 years. The HC2 test result was positive in 33% of the
      patients. Follow-up biopsy was available for 17 of these patients (52%) and for
      25 of the 67 patients (37%) with a negative HC2 result. A total of 5 of the
      patients (29%) with a positive HC2 result and 2 of the patients (8%) with a
      negative HC2 result had CIN/VAIN 3 on follow-up biopsy, a statistically
      insignificant difference (P = .10). Human papillomavirus 16/18 genotypes were
      detected in the CIN/VAIN 2+ lesions of 5 patients with a negative HC2 result.
      CONCLUSIONS: HC2 yielded a false-negative rate of 8% for CIN 3. HC2 testing
      therefore may not be sufficient for triage of patients with an ASC-US
      Papanicolaou test result. Patients with ASC-US during long-term posttherapy
      follow-up need close monitoring, with colposcopic evaluation if clinically
      indicated.

PMID- 25611105
TI  - Performing colonic mast cell counts in patients with chronic diarrhea of unknown
      etiology has limited diagnostic use.
AB  - CONTEXT: Mastocytic enterocolitis is a recently described entity defined by
      chronic diarrhea of unknown etiology and normal colon biopsy results with
      increased mast cells (MCs) seen on special stains. These patients may benefit
      from mast cell stabilizers; however, the clinical utility of MC counts remains
      unknown. OBJECTIVE: To determine the clinical utility of colonic MC counts on
      normal biopsies in patients with chronic diarrhea of unknown etiology. DESIGN:
      Blinded MC counts using a c-Kit stain were performed in 76 consecutive patients
      with chronic diarrhea of unknown etiology who had normal colon biopsy results and
      in 89 consecutive control patients presenting for screening colonoscopy. Mast
      cells were counted per single high-power field in the highest-density area. A t
      test was used to compare the counts, and receiver operating characteristic curves
      were generated to examine sensitive and specific cutoff values. RESULTS: Overall,
      MC counts averaged 31 MCs per high-power field in the study group versus 24 MCs
      per high-power field in the control group (P < .001). When stratified by
      location, a significant increase was seen in biopsies from the left colon only.
      Receiver operating characteristic analysis revealed that overall MC counts, left
      sided MC counts, and the difference between right- and left-sided MC counts did
      not yield discriminatory cutoff values (area under the curve, 0.68, 0.74, and
      0.81, respectively). CONCLUSIONS: Mast cell counts were increased in patients
      with chronic diarrhea of unknown etiology, primarily in the left colon. However,
      receiver operating characteristic analysis demonstrates no discriminatory cutoff
      values. Quantitative MC stains yield little useful diagnostic information, and
      further studies are necessary to determine whether mastocytic enterocolitis truly
      represents a distinct entity.

PMID- 25611106
TI  - Differentiating benign from malignant bone marrow B-cell lymphoid aggregates: a
      statistical analysis of distinguishing features.
AB  - CONTEXT: Lymphoid aggregates are seen in a minority of bone marrow biopsy
      specimens, and when present, their neoplastic nature is often apparent by
      morphologic evaluation. However, the distinction between benign and malignant
      aggregates can be a diagnostic challenge when there are multiple aggregates with
      no documented history of lymphoma. OBJECTIVE: To aid in the distinction between
      benign and malignant B-cell lymphoid aggregates. DESIGN: Previously, we described
      specific distribution patterns for B and T lymphocytes within bone marrow
      aggregates. To statistically analyze the significance of these patterns as well
      as previously reported criteria, we examined 128 bone marrow specimens with
      benign aggregates and 78 specimens with documented malignant B-cell aggregates
      and calculated specific odds ratios (ORs) and 95% confidence intervals (CIs) to
      aid in differentiating between benign and malignant B-cell aggregates. RESULTS:
      Aggregates with infiltrative edges (OR, 80.54; 95% CI, 31.76-204.21), a B-cell
      pattern (OR, 30.08; 95% CI, 13.28-68.10), paratrabecular location (OR, 10.17; 95%
      CI, 3.96-26.12), size greater than 600 MUm (OR, 6.83: 95% CI, 3.61-12.93), or
      cytologic atypia correlated with malignancy. CONCLUSIONS: When taken
      collectively, the presence of more than 2 of these characteristic features was
      strongly predictive of malignancy.

PMID- 25611107
TI  - Cervista HPV HR test for cervical cancer screening: a comparative study in the
      Catalonian population.
AB  - CONTEXT: Almost all cervical cancers are related to the human papillomavirus
      (HPV). Future strategies for cervical cancer screening will be based on HPV
      detection. The Hybrid Capture 2 (HC2) test is currently the most widely used
      method to screen for HPV. OBJECTIVE: To test the performance of the Cervista HPV
      HR test for cervical screening. DESIGN: We examined 875 cervical samples by HC2
      and Cervista. Of these, 64 were high-grade cervical intraepithelial neoplasia
      (CIN 2+) cases and were used to test the sensitivity of the assay. The remaining
      811 were non-CIN 2+ cases, which were used to compare specificity. The
      noninferiority score test was used, with at least 0.90 for sensitivity and 0.98
      for specificity and with a kappa value of 0.7. RESULTS: Sensitivity and
      specificity were, respectively, 100% and 86.4% for the HC2 test, and 98.4% and
      85.2% for the Cervista test. The agreement between the two assays was 91.7% (802
      of 875; kappa = 0.743; 95% confidence interval, 0.688-0.798). The noninferiority
      score test (relative sensitivity of 90%, T = 2.85, P = .002; and relative
      specificity of 98%, T = 2.75, P = .003) demonstrated that the Cervista results
      were not inferior to those of the HC2 test. Intralaboratory and interlaboratory
      reproducibility was determined by evaluating 513 and 507 samples, respectively.
      These reproducibilities showed kappa values of 0.886 (95% confidence interval,
      0.845-0.927) and 0.907 (95% confidence interval, 0.886-0.948), respectively.
      CONCLUSIONS: Our results demonstrate that the Cervista HPV HR test shows the same
      specificity as the HC2 assay. We therefore conclude that the Cervista HPV HR test
      is suitable for cervical cancer screening purposes.

PMID- 25611108
TI  - Systematic review of the effectiveness of fine-needle aspiration and/or core
      needle biopsy for subclassifying lymphoma.
AB  - CONTEXT: The World Health Organization system for lymphoma classification relies
      on histologic findings from excisional biopsies. In contradistinction to expert
      guidelines, practitioners increasingly rely on fine-needle aspiration cytology
      and core needle biopsies rather than excisional biopsies to diagnose lymphomas.
      OBJECTIVE: To determine a rate at which fine-needle aspiration cytology and core
      needle biopsies, combined with flow cytometry and/or genetic techniques, can
      provide a diagnosis sufficient for optimal medical management of lymphoma. DATA
      SOURCES: The English-language literature on fine-needle aspiration cytology and
      core needle biopsies for lymphoma was reviewed to identify studies that provided
      interpretations of all specimens regardless of whether these were deemed
      diagnostic. CONCLUSIONS: Forty-two studies (1989-2012) specified the lymphoma
      subtypes for each diagnosis or indicated a rate at which the methods failed to
      provide a diagnosis. The median rate at which fine-needle aspiration cytology and
      core needle biopsies yielded a subtype-specific diagnosis of lymphoma was 74%.
      Strictly adhering to expert guidelines, which state that follicular lymphoma
      cannot be graded by these techniques, decreased the diagnostic yield further to
      66%. Thus, 25% to 35% of fine-needle aspirates and/or core biopsies of nodes must
      be followed by an excisional lymph node biopsy to fully classify lymphoma.

PMID- 25611109
TI  - Four decades of necrotizing sarcoid granulomatosis: what do we know now?
AB  - CONTEXT: In the 4 decades since Dr Averill A. Liebow introduced necrotizing
      sarcoid granulomatosis, there have been publications of numerous cases, but its
      nature and possible relationship to classical and nodular sarcoidosis have been
      and remain controversial. Liebow introduced necrotizing sarcoid granulomatosis as
      a provisional diagnostic term and stated that "the problem is whether the disease
      represents necrotizing angiitis with sarcoid reaction, or sarcoidosis with
      necrosis of the granulomas and of the vessels." There has, as yet, been no
      definitive answer to the questions that he raised. OBJECTIVE: To determine
      whether there is a relationship between necrotizing sarcoid granulomatosis and
      nodular sarcoidosis in order to ascertain whether the current prevailing opinion
      that they are related is correct. DATA SOURCES: The world's literature on
      necrotizing sarcoid granulomatosis from 1973 to 2013 and nodular sarcoidosis from
      1952 to 2013 was critically reviewed. One hundred three cases of necrotizing
      sarcoid granulomatosis and 111 cases of nodular sarcoidosis were found suitable
      for individual case analysis. CONCLUSIONS: The data showed a striking overlap in
      the clinical, radiologic, and pathologic features of both entities, strongly
      supporting the conclusion that necrotizing sarcoid granulomatosis is a previously
      unrecognized manifestation of sarcoidosis and is essentially the same as nodular
      sarcoidosis. It is proposed that use of necrotizing sarcoid granulomatosis as a
      diagnostic term be discontinued and replaced by sarcoidosis with necrotizing
      sarcoid granulomatosis pattern provided that an infectious etiology can be
      reasonably excluded. Our concept of sarcoidosis should now be expanded to
      recognize that there is a continuous spectrum of necrosis ranging from minimal to
      extensive.

PMID- 25611110
TI  - Endocrine manifestations of von Hippel-Lindau disease.
AB  - von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by
      heterozygous mutations in the VHL tumor suppressor gene that is characterized by
      the occurrence of multiple endocrine and nonendocrine lesions. This review
      focuses on the endocrine manifestations of VHL disease. Pancreatic neuroendocrine
      proliferations (ductuloinsular complexes, islet dysplasia, endocrine
      microadenoma, and neuroendocrine tumors), pheochromocytomas, and extra-adrenal
      paragangliomas are important endocrine manifestations of VHL disease. They
      frequently display characteristic clinical, biochemical, and histopathologic
      features that, although not pathognomonic, can be helpful in suggesting VHL
      disease as the underlying etiology and distinguishing these tumors from sporadic
      cases. Recent improvements in treatment and outcomes of renal cell carcinomas
      have allowed pancreatic neuroendocrine tumors to emerge as a significant source
      of metastatic disease, making the accurate recognition and classification of
      these neoplasms by the pathologist of utmost importance to determine prognosis,
      treatment, and follow-up strategies for affected patients. 

PMID- 25611111
TI  - Undifferentiated embryonal sarcoma of the liver: a concise review.
AB  - Undifferentiated embryonal sarcoma of the liver is an aggressive mesenchymal
      tumor that occurs predominantly in children. Although this entity has been
      described for decades, its pathogenesis is still obscure. Its association with
      mesenchymal hamartoma has been well described on the basis of identical
      chromosomal abnormalities. The clinical and radiological diagnoses are often
      difficult, and the diagnosis of undifferentiated embryonal sarcoma of the liver
      is based on its histology and immunophenotype. It is essential to recognize the
      characteristic histologic findings and the pattern of the immunohistochemistry
      staining to rule out other hepatic lesions. Multimodal therapy with surgery,
      chemotherapy, and radiation therapy has drastically improved the prognosis of
      patients with undifferentiated embryonal sarcoma of the liver. This successful
      management requires timely diagnosis for superior outcome. 

PMID- 25611112
TI  - Pulmonary capillary hemangiomatosis: a rare cause of pulmonary hypertension.
AB  - Pulmonary capillary hemangiomatosis is a rare cause of pulmonary hypertension
      characterized by extensive proliferation of pulmonary capillaries within alveolar
      septae. Clinical presentation is nonspecific and includes dyspnea, cough, chest
      pain, and fatigue. Radiology shows diffuse centrilobular ground-glass opacities.
      Pulmonary capillary hemangiomatosis is clinically and radiographically
      indistinguishable from peripheral venoocclusive disease, making microscopic
      diagnosis essential. Histologically, pulmonary capillary hemangiomatosis shows an
      abnormal proliferation of small, thin-walled capillaries that expand the alveolar
      septae. The endothelial cells that comprise these lesions are cytologically bland
      and show no mitotic activity. Pulmonary capillary hemangiomatosis is important to
      recognize because prostacyclin therapy, a mainstay in the treatment of pulmonary
      hypertension, has been reported to cause sudden respiratory distress and death in
      these patients. Prognosis of this disease remains poor, and the only definitive
      treatment is lung transplantation. 

PMID- 25611113
TI  - Splenic lymphangioma.
AB  - Splenic lymphangioma is a rare malformation of the splenic lymphatic channels,
      mostly seen in children. It is characterized by the presence of cysts, resulting
      from increases in the size and number of thin-walled lymphatic vessels that are
      abnormally interconnected and dilated. The condition may be restricted to the
      spleen, but in most cases it involves multiple organs (systemic
      lymphangiomatosis). The clinical picture is variable; small lesions are often
      incidentally detected through imaging studies, while larger lesions can result in
      compression of organs, causing pain or rupture even after minor trauma.
      Therefore, splenic lymphangiomas should be considered in the differential
      diagnosis of splenomegaly or left upper quadrant pain even among adults and
      should be immediately treated with splenectomy; delay in the therapeutic
      intervention can lead to life-threatening complications. 

PMID- 25611114
TI  - Why does rate of bone density loss not predict fracture risk?
AB  - CONTEXT: Intuitively, rapid bone mineral density (BMD) loss should predict
      fracture risk independently of current BMD, but studies have not confirmed this.
      We hypothesized that measurement error when characterizing rates of BMD loss
      might explain this paradox. OBJECTIVE: To examine the importance of measurement
      error in predicting BMD loss. DESIGN AND SETTING: Retrospective registry study
      using BMD results for Manitoba, Canada. PATIENTS: Untreated women age 50 years
      and older with three femoral neck BMD tests. MAIN OUTCOME MEASURES: Correlation
      in annualized rates of BMD change for interval 1 (first to second scan) versus
      interval 2 (second to third scan) with confirmatory model-based simulations that
      varied measurement error and testing intervals. RESULTS: Five hundred forty two
      women with a mean age of 62 years had BMD measurements separated by a mean of 3.5
      years for interval 1 and 3.4 years for interval 2. Mean femoral neck BMD loss was
      stable (-0.5% per year for interval 1, -0.6% per year for interval 2) with a weak
      negative correlation between intervals (r = -0.11, P = .01). There were no
      significant correlations for BMD change at the total hip (r = 0.01, P = .74) or
      total spine (r = -0.01, P = .77). Simulations showed low explained variation for
      BMD change between intervals 1 and 2 (<20%). To explain 50% of the variation of
      BMD change between intervals 1 and 2 required a BMD measurement error <= 0.008
      g/cm(2) or a BMD testing interval >= 5 years. CONCLUSIONS: The low correlation
      between past and future BMD loss helps explain why the rate of BMD loss is
      unlikely to be helpful for refining fracture risk.

PMID- 25611115
TI  - Assessment of Closure Competency of Sutureless Vitrectomy Sclerotomies After
      Scleral Hydration.
AB  - PURPOSE: To assess the influence that hydration applied on the sclerotomy edges
      may have on incisional closure resistance after transconjunctival sutureless
      vitrectomy (TSV). METHODS: Experimental, randomized and observer-masked study in
      which 23-gauge TSV was performed in 80 cadaveric pig eyes. Once each vitrectomy
      was finished, hydration with balanced salt solution (BSS) was applied on the
      sclerotomy edges of one of the superior incision sites; no maneuver was performed
      on the other superior sclerotomy. Intraocular pressure (IOP) was gradually
      increased by means of the vitrectomy system (Accurus; Alcon Laboratories, TX)
      until one of the superior sclerotomies opened, allowing internal ocular solution
      to escape. RESULTS: In 45% of cases (36 of 80 eyes), sclerotomies subjected to
      hydration allowed intraocular fluid escape (p = 0.43). There were no differences
      when comparing opening pressure values of hydrated and non-hydrated sclerotomies
      (p = 0.19). CONCLUSIONS: Scleral hydration did not demonstrate increase in the
      sclerotomy closure resistance in our experimental model. Given the widespread use
      of sutureless TSV around the world, the results obtained in our research, in
      spite of being negative, may contribute to the knowledge of the behavior of
      sutureless sclerotomies.

PMID- 25611117
TI  - Long-range seasonal migration in insects: mechanisms, evolutionary drivers and
      ecological consequences.
AB  - Myriad tiny insect species take to the air to engage in windborne migration, but
      entomology also has its 'charismatic megafauna' of butterflies, large moths,
      dragonflies and locusts. The spectacular migrations of large day-flying insects
      have long fascinated humankind, and since the advent of radar entomology much has
      been revealed about high-altitude night-time insect migrations. Over the last
      decade, there have been significant advances in insect migration research, which
      we review here. In particular, we highlight: (1) notable improvements in our
      understanding of lepidopteran navigation strategies, including the hitherto
      unsuspected capabilities of high-altitude migrants to select favourable winds and
      orientate adaptively, (2) progress in unravelling the neuronal mechanisms
      underlying sun compass orientation and in identifying the genetic complex
      underpinning key traits associated with migration behaviour and performance in
      the monarch butterfly, and (3) improvements in our knowledge of the multifaceted
      interactions between disease agents and insect migrants, in terms of direct
      effects on migration success and pathogen spread, and indirect effects on the
      evolution of migratory systems. We conclude by highlighting the progress that can
      be made through inter-phyla comparisons, and identify future research areas that
      will enhance our understanding of insect migration strategies within an eco
      evolutionary perspective. 

PMID- 25611116
TI  - Feasibility of integrating mental health screening and services into routine
      elder abuse practice to improve client outcomes.
AB  - The goal of this pilot program was to test the feasibility of mental health
      screening among elder abuse victims and of offering those victims a brief
      psychotherapy for depression and anxiety. Elder abuse victims who sought
      assistance from a large, urban elder abuse service were screened for depression
      and anxiety using standardized measures. Clients with clinically significant
      depression (PHQ-9) or anxiety (GAD-7) were randomized to receive one of three
      different interventions concurrent with abuse resolution services. Staff were
      able to screen 315 individuals, with 34% of clients scoring positive for
      depression or anxiety. Of those with mental health needs, only 15% refused all
      services. The mental health intervention (PROTECT) was successfully implemented
      in two different formats with collaboration between staff workers. These findings
      support both the need for mental health care among elder abuse victims and the
      feasibility of integrating mental health screening and treatment into routine
      elder abuse practice. 

PMID- 25611118
TI  - Living alongside more affluent neighbors predicts greater involvement in
      antisocial behavior among low-income boys.
AB  - BACKGROUND: The creation of economically mixed communities has been proposed as
      one way to improve the life outcomes of children growing up in poverty. However,
      whether low-income children benefit from living alongside more affluent neighbors
      is unknown. METHOD: Prospectively gathered data on over 1,600 children from the
      Environmental Risk (E-Risk) Longitudinal Twin Study living in urban environments
      is used to test whether living alongside more affluent neighbors (measured via
      high-resolution geo-spatial indices) predicts low-income children's antisocial
      behavior (reported by mothers and teachers at the ages of 5, 7, 10, and 12).
      RESULTS: Results indicated that low-income boys (but not girls) surrounded by
      more affluent neighbors had higher levels of antisocial behavior than their peers
      embedded in concentrated poverty. The negative effect of growing up alongside
      more affluent neighbors on low-income boys' antisocial behavior held across
      childhood and after controlling for key neighborhood and family-level factors.
      CONCLUSIONS: Findings suggest that efforts to create more economically mixed
      communities for children, if not properly supported, may have iatrogenic effects
      on boys' antisocial behavior.

PMID- 25611119
TI  - Tandem analysis of transcriptome and proteome changes after a single dose of
      corticosteroid: a systems approach to liver function in pharmacogenomics.
AB  - Corticosteroids (CS) such as methylprednisolone (MPL) affect almost all liver
      functions through multiple mechanisms of action, and long-term use results in
      dysregulation causing diverse side effects. The complexity of involved molecular
      mechanisms necessitates a systems approach. Integration of information from the
      transcriptomic and proteomic responses has potential to provide deeper insights
      into CS actions. The present report describes the tandem analysis of rich time
      series transcriptomic and proteomic data in rat liver after a single dose of MPL.
      Hierarchical clustering of the common genes represented in both mRNA and protein
      datasets displayed two dominant patterns. One of these patterns exhibited
      complementary mRNA and protein expression profiles indicating that MPL affected
      the regulation of these genes at the transcriptional level. Some of the classic
      pharmacodynamic markers for CS actions, including tyrosine aminotransferase
      (TAT), were among this group, together with genes encoding urea cycle enzymes and
      ribosomal proteins. The other pattern was rather unexpected. For this group of
      genes, MPL had distinctly observable effects at the protein expression level,
      although a change in the reverse direction occurred at the transcriptional level.
      These genes were functionally associated with metabolic processes that might be
      essential to elucidate side effects of MPL on liver, most importantly including
      modulation of oxidative stress, fatty acid oxidation, and bile acid biosynthesis.
      Furthermore, profiling of gene and protein expression data was also done
      independently of one another by a two-way sequential approach. Prominent temporal
      shifts in expression and relevant cellular functions were described together with
      the assessment of changes in the complementary side. 

PMID- 25611120
TI  - Protein design of IgG/TCR chimeras for the co-expression of Fab-like moieties
      within bispecific antibodies.
AB  - Immunoglobulins and T cell receptors (TCRs) share common sequences and
      structures. With the goal of creating novel bispecific antibodies (BsAbs), we
      generated chimeric molecules, denoted IgG_TCRs, where the Fv regions of several
      antibodies were fused to the constant domains of the alpha/beta TCR. Replacing
      CH1 with Calpha and CL with Cbeta, respectively, was essential for achieving at
      least partial heavy chain/light chain assembly. Further optimization of the
      linker regions between the variable and constant domains, as well as replacement
      of the large FG loop of Cbeta with a canonical beta-turn, was necessary to
      consistently obtain full heavy chain/light chain assembly. The optimized IgG_TCR
      molecules were evaluated biophysically and shown to maintain the binding
      properties of their parental antibodies. A few BsAbs were generated by co
      expressing native Fabs and IgG_TCR Fabs within the same molecular construct. We
      demonstrate that the IgG_TCR designs steered each of the light chains within the
      constructs to specifically pair with their cognate heavy chain counterparts. We
      did find that even with complete constant domain specificity between the CH1/CL
      and Calpha/Cbeta domains of the Fabs, strong variable domain interactions can
      dominate the pairing specificity and induce some mispairing. Overall, the IgG_TCR
      designs described here are a first step toward the generation of novel BsAbs that
      may be directed toward the treatment of multi-faceted and complex diseases. 

PMID- 25611121
TI  - Prevalence of hepatitis C virus in mothers and their children in Malawi.
AB  - OBJECTIVES: Hepatitis C virus (HCV) prevalence is poorly mapped in the East
      African region; with the advent of novel HCV therapies, better epidemiological
      data are required to target the infection. We sought to estimate HCV prevalence
      in healthy Malawian mothers and assess mother-to-child transmission (MTCT);
      context is provided by reviewing previously published HCV prevalence data from
      the region. METHODS: Using ELISA screening and confirmatory blot, serological
      testing of 418 healthy Malawian mothers for HCV was performed. To examine MTCT,
      the children of any positive women were also tested for HCV; all children had
      malignant disease unrelated to hepatocellular carcinoma. We compared our results
      to published literature on HCV prevalence in Malawi and its neighbouring
      countries. RESULTS: Three of 418 women were HCV reactive by ELISA; two were
      confirmed positive by immunoblot (0.5%). One child of an HCV-infected mother was
      HCV seropositive. The literature review revealed HCV prevalence ranging from 0 to
      7.2% in the region, being highest in Tanzania and specifically for cohorts of
      inpatients and HIV-co-infected people. The overall estimated prevalence of HCV in
      Malawi was 1.0% (95%CI 0.7-1.4) when all studies were included (including this
      one), but lower in healthy cohorts alone at 0.3% (95%CI 0.1-1.2). CONCLUSIONS:
      This is the first study using confirmatory tests to examine HCV prevalence in
      healthy Malawian mothers; the prevalence was low. Future studies need to address
      the source of infection in healthy women.

PMID- 25611122
TI  - Clinical Assessment Versus MRI Diagnosis of Meniscus Tears.
AB  - CLINICAL SCENARIO: Common injuries in high-level and recreational athletes,
      nonathletes, and the elderly are medial and lateral meniscus tears. Diagnosis of
      meniscus tears is done with clinical exam, magnetic resonance imaging (MRI), and
      arthroscopy. The gold standard is arthroscopy, but accuracy of a clinical exam
      versus MRI diagnosis of meniscus tears is in question. A clinician's ability to
      detect a meniscus tear is beneficial to the patient from a timing standpoint. The
      process of obtaining an MRI and results could be lengthy, but if the meniscus
      tear is accurately diagnosed clinically, the patient could be suspended from
      athletics or specific job duties to prevent further injury. In addition,
      rehabilitation could be initiated immediately, resulting in better outcomes for
      the patient. The ability to diagnose a meniscus tear clinically could initiate
      the rehabilitation process much sooner than waiting for MRI testing and results.
      Beginning the rehabilitation phase earlier may lead to faster postoperative
      rehabilitation and better patient outcomes. Clinical detection of a meniscus tear
      will facilitate possible suspension, early treatment, and rehabilitation
      recommendations, but the MRI will provide more specific information about the
      injury, including type and location of tear. Thus, surgical decisions such as
      operative versus nonoperative or meniscectomy versus repair would be based on MRI
      results. Focused Clinical Question: Is a clinical exam as accurate as an MRI scan
      for diagnosing meniscus tears?

PMID- 25611123
TI  - Treatment outcome results from the Bulgarian Acromegaly Database: adjuvant
      dopamine agonist therapy is efficient in less than one fifth of non-irradiated
      patients.
AB  - OBJECTIVE: We described biochemical outcome in regards to different treatment
      modalities in patients with acromegaly in Bulgaria. PATIENTS AND METHODS: It was
      a retrospective analysis using data from the Bulgarian Acromegaly Database.
      Patients with eligible data on at least one treatment modality were included in
      the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF
      1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51)
      years after diagnosis. RESULTS: We identified 534 patients with interpretable
      data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant
      bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with
      disease control achieved in 18.8% and 31.4% respectively. Patients without prior
      radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of
      response to dopamine agonist (DA) therapy were disease activity, radiotherapy and
      medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical
      control in 38.6% of 70 patients. Combination of SSA and cabergoline led to
      remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone
      or in combination resulted in remission in 61.5% of 13 patients. Approximately
      one third of the patients were cured median 10 years after irradiation. Overall
      disease control was observed in 51.4% of our patients increasing to 70.3% in the
      last 5 years of the study period. CONCLUSION: DAs are efficient in less than 20%
      of non-irradiated patients. They are a good cost-effective alternative for
      carefully selected patients.

PMID- 25611124
TI  - Automatic bone segmentation and bone-cartilage interface extraction for the
      shoulder joint from magnetic resonance images.
AB  - We present a statistical shape model approach for automated segmentation of the
      proximal humerus and scapula with subsequent bone-cartilage interface (BCI)
      extraction from 3D magnetic resonance (MR) images of the shoulder region. Manual
      and automated bone segmentations from shoulder MR examinations from 25 healthy
      subjects acquired using steady-state free precession sequences were compared with
      the Dice similarity coefficient (DSC). The mean DSC scores between the manual and
      automated segmentations of the humerus and scapula bone volumes surrounding the
      BCI region were 0.926  +/-  0.050 and 0.837  +/-  0.059, respectively. The mean
      DSC values obtained for BCI extraction were 0.806  +/-  0.133 for the humerus and
      0.795  +/-  0.117 for the scapula. The current model-based approach successfully
      provided automated bone segmentation and BCI extraction from MR images of the
      shoulder. In future work, this framework appears to provide a promising avenue
      for automated segmentation and quantitative analysis of cartilage in the
      glenohumeral joint.

PMID- 25611125
TI  - Statistical Theory of Low-Energy Reactive Collisions of N(+) Ions with H2, D2,
      and HD Molecules.
AB  - A statistical treatment is presented of reactive collisions involving N(+) ions
      in the (3)Pja state with H2, D2, and HD molecules in rotation level j of the
      ground vibration state, leading to either the reaction products H + NH(+), D +
      ND(+), and D + NH(+) or H + ND(+). Unlike previous theoretical work, the fine
      structure states of the N(+) ions are treated on an equal footing with other
      internal motions. The calculated cross sections for a given ion energy are
      averaged over a thermal distribution of initial fine-structure states of N(+) for
      a temperature of 300 K and over a thermal distribution of both the internal
      rotation states and translation energy of H2, D2, and HD for temperatures of 305
      and 105 K in order to facilitate a comparison with experiment. The results are
      presented for a range of collision energies from 10 meV to 1 eV. 

PMID- 25611126
TI  - Transcontinental migratory connectivity predicts parasite prevalence in breeding
      populations of the European barn swallow.
AB  - Parasites exert a major impact on the eco-evolutionary dynamics of their hosts
      and the associated biotic environment. Migration constitutes an effective means
      for long-distance invasions of vector-borne parasites and promotes their rapid
      spread. Yet, ecological and spatial information on population-specific host
      parasite connectivity is essentially lacking. Here, we address this question in a
      system consisting of a transcontinental migrant species, the European barn
      swallow (Hirundo rustica) which serves as a vector for avian endoparasites in the
      genera Plasmodium, Haemoproteus and Leucocytozoon. Using feather stable isotope
      ratios as geographically informative markers, we first assessed migratory
      connectivity in the host: Northern European breeding populations predominantly
      overwintered in dry, savannah-like habitats in Southern Africa, whereas Southern
      European populations were associated with wetland habitats in Western Central
      Africa. Wintering areas of swallows breeding in Central Europe indicated a
      migratory divide with both migratory programmes occurring within the same
      breeding population. Subsequent genetic screens of parasites in the breeding
      populations revealed a link between the host's migratory programme and its
      parasitic repertoire: controlling for effects of local breeding location,
      prevalence of Africa-transmitted Plasmodium lineages was significantly higher in
      individuals overwintering in the moist habitats of Western Central Africa, even
      among sympatrically breeding individuals with different overwintering locations.
      For the rarer Haemoproteus parasites, prevalence was best explained by breeding
      location alone, whereas no clear pattern emerged for the least abundant parasite
      Leucocytozoon. These results have implications for our understanding of spatio
      temporal host-parasite dynamics in migratory species and the spread of avian
      borne diseases.

PMID- 25611127
TI  - Changes in blood aggregation with differences in molecular weight and degree of
      deacetylation of chitosan.
AB  - Because the molecular weight (Mw) and degree of deacetylation (DDA) of chitosan
      can vary depending on the purification method, the identification of appropriate
      chitosan structures is important for developing more effective hemostatic agents.
      In this study, the influence of varying Mw and DDA of chitosan on blood
      aggregation was characterized by 10 types of chitosan with different Mw and DDA,
      including oligomers. The highest aggregation of whole blood, washed erythrocytes
      and platelets in platelet-rich plasma (PRP) were observed in chitosan with Mw of
      8.6 kDa or more and with DDA of 75 to 88%. However, chitosan with too high Mw
      (247 kDa) inhibited the aggregation of whole blood, washed erythrocytes and PRP
      at high chitosan concentration. At certain concentrations, chitosan with 75-85%
      DDA and 50-190 kDa and chitosan with 87.6% DDA and 247 kDa both aggregated
      proteins in PRP. Chitosan oligomer did not affect blood aggregation. The results
      suggested that the aggregation by chitosan depended on the interaction of
      positively charged chitosan with negatively charged erythrocytes, platelets and
      plasma protein. It seemed that a suitable balance of positive charge in chitosan
      and negative charge in hemocytes and some kinds of proteins was important. To
      develop a hemostatic with effective blood aggregation, the chitosan should not be
      limited to a single Mw and a single DDA but may be a mixed chitosan with wide
      range of Mw (8.6-247 kDa) and DDA of 75 to 88%. 

PMID- 25611128
TI  - A power pack based on organometallic perovskite solar cell and supercapacitor.
AB  - We present an investigation on a power pack combining a CH3NH3PbI3-based solar
      cell with a polypyrrole-based supercapacitor and evaluate its performance as an
      energy pack. The package achieved an energy storage efficiency of 10%, which is
      much higher than that of other systems combining a PV cell with a supercapacitor.
      We find a high output voltage of 1.45 V for the device under AM 1.5G illumination
      when the CH3NH3PbI3-based solar cell is connected in series with a polypyrrole
      based supercapacitor. This system affords continuous output of electric power by
      using CH3NH3PbI3-based solar cell as an energy source mitigating transients
      caused by light intensity fluctuations or the diurnal cycle. 

PMID- 25611130
TI  - Energy-cascade organic photovoltaic devices incorporating a host-guest
      architecture.
AB  - In planar heterojunction organic photovoltaic devices (OPVs), broad spectral
      coverage can be realized by incorporating multiple molecular absorbers in an
      energy-cascade architecture. Here, this approach is combined with a host-guest
      donor layer architecture previously shown to optimize exciton transport for the
      fluorescent organic semiconductor boron subphthalocyanine chloride (SubPc) when
      diluted in an optically transparent host. In order to maximize the absorption
      efficiency, energy-cascade OPVs that utilize both photoactive host and guest
      donor materials are examined using the pairing of SubPc and boron
      subnaphthalocyanine chloride (SubNc), respectively. In a planar heterojunction
      architecture, excitons generated on the SubPc host rapidly energy transfer to the
      SubNc guest, where they may migrate toward the dissociating, donor-acceptor
      interface. Overall, the incorporation of a photoactive host leads to a 13%
      enhancement in the short-circuit current density and a 20% enhancement in the
      power conversion efficiency relative to an optimized host-guest OPV combining
      SubNc with a nonabsorbing host. This work underscores the potential for further
      design refinements in planar heterojunction OPVs and demonstrates progress toward
      the effective separation of functionality between constituent OPV materials. 

PMID- 25611129
TI  - Binocular iPad treatment of amblyopia for lasting improvement of visual acuity.

PMID- 25611131
TI  - 1,19-seco-Avermectin analogues from a DeltaaveCDE mutant Streptomyces
      avermectinius strain.
AB  - Three new 1,19-seco-avermectin (AVE) analogues were isolated from the DeltaaveCDE
      mutant Streptomyces avermectinius strain. Their structures were elucidated by
      detailed spectroscopic analysis. This is the first report of 1,19-seco-AVE
      analogues. In an in vitro assay these compounds displayed cytotoxicity against
      Saos-2, MG-63, and B16 cell lines. 

PMID- 25611132
TI  - Optimizing high-risk care management.

PMID- 25611133
TI  - Detection and imaging of aggressive cancer cells using an epidermal growth factor
      receptor (EGFR)-targeted filamentous plant virus-based nanoparticle.
AB  - Molecular imaging approaches and targeted drug delivery hold promise for earlier
      detection of diseases and treatment with higher efficacy while reducing side
      effects, therefore increasing survival rates and quality of life. Virus-based
      nanoparticles are a promising platform because their scaffold can be manipulated
      both genetically and chemically to simultaneously display targeting ligands while
      carrying payloads for diagnosis or therapeutic intervention. Here, we displayed a
      12-amino-acid peptide ligand, GE11 (YHWYGYTPQNVI), on nanoscale filaments formed
      by the plant virus potato virus X (PVX). Bioconjugation was used to produce
      fluorescently labeled PVX-GE11 filaments targeted toward the epidermal growth
      factor receptor (EGFR). Cell detection and imaging was demonstrated using human
      skin epidermoid carcinoma, colorectal adenocarcinoma, and triple negative breast
      cancer cell lines (A-431, HT-29, MDA-MB-231), all of which upregulate EGFR to
      various degrees. Nonspecific uptake in ductal breast carcinoma (BT-474) cells was
      not observed. Furthermore, co-culture experiments with EGFR(+) cancer cells and
      macrophages indicate successful targeting and partitioning toward the cancer
      cells. This study lays a foundation for the development of EGFR-targeted
      filaments delivering contrast agents for imaging and diagnosis, and/or toxic
      payloads for targeted drug delivery. 

PMID- 25611134
TI  - Design, synthesis, and characterization of hybrid metal-ligand hydrogen-bonded
      (MLHB) supramolecular architectures.
AB  - Despite the prevalence of supramolecular architectures derived from metal-ligand
      or hydrogen-bonding interactions, few studies have focused on the simultaneous
      use of these two strategies to form discrete assemblies. Here we report the use
      of a supramolecular tecton containing both metal-binding and self-complementary
      hydrogen-bonding interactions that upon treatment with metal precursors assembles
      into discrete hybrid metal-ligand hydrogen-bonded assemblies with closed
      topology. (1)H NMR DOSY experiments established the stability of the structures
      in solution, and the measured hydrodynamic radii match those determined
      crystallographically, suggesting that the closed topology is maintained both in
      solution and in the solid state. Taken together, these results demonstrate the
      validity of using both hydrogen-bonding and metal-ligand interactions to form
      stable supramolecular architectures. 

PMID- 25611136
TI  - Cervical spinal cord stimulation treatment of deafferentation pain from brachial
      plexus avulsion injury complicated by complex regional pain syndrome.
AB  - Brachial plexus avulsion is a rare and debilitating condition frequently
      associated with severe, intractable neuropathic pain. Interventional treatment
      modalities include dorsal root entry zone lesioning, stellate ganglion blockade,
      and neuromodulation such as spinal cord stimulation. We present a case of a 42
      year-old woman with a traumatic left upper extremity brachial plexus avulsion
      injury after a motor vehicle accident and treatment of deafferentation pain
      complicated by complex regional pain syndrome type II. Previous unsuccessful
      interventions included repeated stellate ganglion blocks, transcutaneous
      electrical nerve stimulation, and opioid medication. After a successful trial of
      cervical spinal cord stimulator lead placement, she went on to an uneventful
      permanent implantation procedure. Spinal cord stimulation is an effective
      treatment for deafferentation pain and complex regional pain syndrome type II
      secondary to brachial plexopathy refractory to pharmacotherapy and conventional
      interventional attempts to modulate pain. 

PMID- 25611137
TI  - Attempting to prevent persistent postamputation phantom limb and stump pain.
AB  - Persistent postsurgical pain after amputation is common and has a number of
      proposed risk factors. We describe the management of a patient with persistent
      pain after a below-the-knee amputation. We used a combination of general,
      peripheral, and neuraxial anesthesia techniques to control postoperative phantom
      limb and stump pain in a patient at high risk for developing chronic pain. With
      preemptive management and mechanism-directed therapies, adequate preoperative and
      postoperative pain control were achieved in attempts to reduce the risk of
      chronic phantom limb pain. 

PMID- 25611135
TI  - Structure and thermodynamics of N6-methyladenosine in RNA: a spring-loaded base
      modification.
AB  - N(6)-Methyladenosine (m(6)A) modification is hypothesized to control processes
      such as RNA degradation, localization, and splicing. However, the molecular
      mechanisms by which this occurs are unclear. Here, we measured structures of an
      RNA duplex containing m(6)A in the GGACU consensus, along with an unmodified RNA
      control, by 2D NMR. The data show that m(6)A-U pairing in the double-stranded
      context is accompanied by the methylamino group rotating from its energetically
      preferred syn geometry on the Watson-Crick face to the higher-energy anti
      conformation, positioning the methyl group in the major groove. Thermodynamic
      measurements of m(6)A in duplexes reveal that it is destabilizing by 0.5-1.7
      kcal/mol. In contrast, we show that m(6)A in unpaired positions base stacks
      considerably more strongly than the unmodified base, adding substantial
      stabilization in single-stranded locations. Transcriptome-wide nuclease mapping
      of methylated RNA secondary structure from human cells reveals a structural
      transition at methylated adenosines, with a tendency to single-stranded structure
      adjacent to the modified base. 

PMID- 25611138
TI  - Ventricular pacing for induced hypotension in a toddler.
AB  - Cerebral aneurysm clipping may require periods of hypotension to facilitate
      dissection and clip application. We describe the use of rapid ventricular pacing
      to facilitate establishment of controlled hypotension for an 18-month-old child
      during clipping for giant basilar artery aneurysm. This technique is an
      alternative to pharmacologic means of inducing hypotension for neurosurgical
      procedures and has not been previously described in children. 

PMID- 25611139
TI  - Dexmedetomidine suppressed involuntary movement in a patient with cerebral palsy.
AB  - Involuntary movements in patients with cerebral palsy can interfere with invasive
      procedures performed under sedation. We present a case of a 58-year-old man with
      cerebral palsy, who successfully underwent a cardiac catheterization while
      sedated with IV dexmedetomidine. The patient's involuntary movements were
      suppressed, which allowed the cardiologist to perform the procedure on an
      immobile, cooperative patient, all while maintaining patient comfort, stable
      hemodynamics, as well as adequate oxygenation and ventilation. This novel use of
      dexmedetomidine might facilitate monitored anesthesia care in patients otherwise
      requiring general anesthesia. 

PMID- 25611142
TI  - Can Modified Kurokawa's Double-Door Laminoplasty Reduce the Incidence of Axial
      Symptoms at Long-term Follow-up?: A Prospective Study of 152 Patients With
      Cervical Spondylotic Myelopathy.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: The purpose of this study
      was to determine whether the modified procedure reduces long-term axial symptoms
      (AS) and to understand better why the AS occur. SUMMARY OF BACKGROUND DATA:
      Following Kurokawa's double-door laminoplasty, postoperative AS reduce the
      quality of life of patients with cervical spondylotic myelopathy. The etiology of
      AS remains unclear. Some studies report that preservation of the C7 spinous
      process can reduce the frequency of AS. The modified Kurokawa procedure prevents
      AS by preserving the semispinalis cervicis insertion in the spinous process of
      C2. However, it remains unclear whether the modified procedure lowers the
      incidence of AS in the long term (ie, >3 y). MATERIALS AND METHODS: This
      prospective cohort study investigated preoperative and postoperative v, cervical
      intervertebral range of motion, postoperative neurological recovery, neck
      disability index, visual analog scale, surgical cost, and time and blood loss.
      RESULTS: Both groups had satisfied improvement of neurological functions
      (P>0.05). At 3 months and 1 year after surgery, the difference in frequency
      between no symptoms and mild/severe symptoms was significant (traditional group,
      39.06%; modified group, 20.45%) (P<0.05). Interestingly, 3 years after surgery,
      there were no significant between-group differences (P>0.05). CONCLUSIONS: This
      modified approach reduced the incidence of postoperative ASs at 3 months and 1
      year after the operation; however, the between-group difference was not
      significantly different at the 3-year follow-up. The reason for this finding is
      unclear; it may indicate that the incidence of AS is caused by other factors,
      such as the preservation of the C7 spinous process rather than the C2 spinous
      process.

PMID- 25611146
TI  - Accuracy of the Free-hand Placement of Pedicle Screws in the Lumbosacral Spine
      Using a Universal Entry Point: Clinical Validation.
AB  - STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To evaluate the
      accuracy of the free-hand placement of pedicle screws (PSs) using a new method of
      localization of entry points. SUMMARY OF BACKGROUND DATA: The PSs are essential
      in modern spinal surgery but their placement can be technically demanding. To
      improve this accuracy, numerous aids have been developed, some of them
      technologically advanced. Despite advances in technology the free-hand technique
      is still very popular. A simple geometric method of localization of entry points
      is proposed, designed to improved anatomic orientation. METHODS: The radiographic
      and clinical data of 92 consecutive patients who underwent primary placement of
      PS in the lumbar spine were retrospectively analyzed. Postoperative computed
      tomography scans were used to assess the accuracy of screw placement using both
      quantitative and anatomic criteria. RESULTS: A total of 85 patients with 410
      screws were included in the study. Twenty screws were malpositioned, thus the
      overall accuracy was 95.12%. Of all levels instrumented the breach rate for the
      L1 level was highest (21.43%) and the difference was statistically significant.
      Two screws in 2 patients were symptomatic, causing radicular pain. Both underwent
      successful revisions. CONCLUSIONS: The proposed method of PS placement is safe
      and reliable for all levels from L2 to S1, with the accuracy similar to image
      guided navigation systems.

PMID- 25611150
TI  - Impact of HIV on lung tumorigenesis in an animal model.
AB  - Many HIV patients on antiretroviral therapy have controlled viremia and restored
      (albeit partially) immunity. Yet, they have high rates of lung cancer, even after
      controlling for smoking. We tested the hypothesis that HIV proteins accelerate
      development/progression of lung cancer in an immunocompetent HIV transgenic mouse
      model. The expression of HIV proteins did not enhance lung tumorigenesis caused
      by two different tobacco carcinogens, suggesting that incompletely restored
      immunity and/or inflammation, which persist(s) in most HIV patients despite
      controlled viremia, underlie(s) excess risk of lung cancer. Adjuvant therapies
      that restore immunity and lower inflammation may decrease lung cancer mortality
      in HIV patients. 

PMID- 25611151
TI  - Ultrasound use in the pediatric airway: the time has come.
AB  - Advancements in ultrasonography and increasing familiarity with its use in the
      operating room (vascular access and regional neural blockade) suggest its
      feasibility as an adjunct in pediatric airway evaluation and intervention. We
      report 3 cases demonstrating the usefulness of ultrasound techniques in this
      setting. We show key elements of airway anatomy, noninvasive observation of vocal
      cord motion, and percutaneous periglottic steroid injection via the cricothyroid
      membrane in 3 different patients. This report reveals the possible usefulness of
      ultrasound imaging in clinical anesthesia care, specifically airway management,
      in children. 

PMID- 25611149
TI  - Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural
      mechanism regulating shifts in cognitive states of HIV-infected patients.
AB  - OBJECTIVES: To identify prognostic surrogate markers for change in cognitive
      states of HIV-infected patients. DESIGN: Longitudinal cerebrospinal fluid (CSF)
      samples were collected from 98 HIV-infected patients identified by temporal
      change in cognitive states classified as normal, stably impaired, improving and
      worsening. METHODS: The metabolic composition of CSF was analysed using H nuclear
      magnetic resonance (H NMR) spectroscopy that focused on energy metabolites.
      Metabolic biomarkers for cognitive states were identified using multivariate
      partial least squares regression modelling of the acquired spectra, combined with
      nonparametric analyses of metabolites with clinical features. RESULTS:
      Multivariate modelling and cross-validated recursive partitioning identified
      several energy metabolites that, when combined with clinical variables,
      classified patients based on change in neurocognitive states. Prognostic
      identification for worsening was achieved with four features that included no
      change in a detectable plasma viral load, elevated citrate and acetate; decreased
      creatine, to produce a model with a predictive accuracy of 92%, sensitivity of
      88% and 96% specificity. Prognosis for improvement contained seven features that
      included first visit age less than 47 years, new or continued use of
      antiretrovirals, elevated glutamine and glucose; decreased myo-inositol, beta
      glucose and creatinine to generate a model with a predictive accuracy of 92%,
      sensitivity of 100% and specificity of 84%. CONCLUSION: These CSF metabolic
      results suggest that worsening cognitive status in HIV-infected patients is
      associated with increased aerobic glycolysis, and improvements in cognitive
      status are associated with a shift to anaerobic glycolysis. Dietary, lifestyle
      and pharmacologic interventions that promote anaerobic glycolysis could protect
      the brain in setting of HIV infection with combined antiretroviral therapy.

PMID- 25611152
TI  - Editorial comment: ultrasound use in the pediatric airway: the time has come.

PMID- 25611153
TI  - Two lessons from the empiric management of a combined overdose of liraglutide and
      amitriptyline.
AB  - We report the case of a 52-year-old man with a combined liraglutide and
      amitriptyline overdose who presented with a seizure and then pulseless electrical
      activity cardiac arrest. This is the largest reported overdose of liraglutide (36
      mg), a novel glucagon-like peptide-1 analog recommended for certain patients with
      type 2 diabetes mellitus. The subsequent biochemical effects included severe
      electrolyte disturbances associated with polyuria. Regarding the amitriptyline,
      treatment with lipid emulsion correlated with resolution of electrocardiographic
      changes and successful resuscitation. The treatment of amitriptyline overdose
      with lipid emulsion is briefly discussed. 

PMID- 25611154
TI  - Platypnea-orthodeoxia: a rare complication after repair of a contained rupture of
      an abdominal aortic aneurysm.
AB  - After open repair of a contained rupture of a giant abdominal aortic aneurysm,
      the patient, a 67-year-old man, developed respiratory insufficiency, and his
      hemoglobin oxygen saturation dramatically decreased when his position was changed
      from supine to upright. Transesophageal echocardiography revealed platypnea
      orthodeoxia syndrome due to a patent foramen ovale and subsequent right-to-left
      shunting despite normal intracardiac pressures. After interventional patent
      foramen ovale closure, the patient could be separated from the respirator without
      difficulty. 

PMID- 25611155
TI  - Severe anaphylaxis: the secret ingredient.
AB  - In this case report, we describe a healthy urological patient who suffered severe
      intraoperative anaphylaxis to chlorhexidine, an ingredient contained in
      frequently used lubricants (Instillagel, Endosgel). Chlorhexidine is a well-known
      skin disinfectant and antiseptic component in mouthwash or other over the counter
      antiseptic pharmaceuticals. There is little awareness that commonly used
      lubricants may contain hidden chlorhexidine. After severe intraoperative
      anaphylaxis, it is important to investigate all potential (including hidden)
      agents that might have caused this life-threatening reaction. 

PMID- 25611156
TI  - N-doped graphene nanoribbons as efficient metal-free counter electrodes for
      disulfide/thiolate redox mediated DSSCs.
AB  - Nitrogen-doped graphene nanoribbons (N-GNRs) were prepared by thermal treatment
      of the as-zipped graphene oxide nanoribbons in NH3 gas. X-ray photoelectron
      spectroscopy (XPS) measurements revealed a high nitrogen content up to 6.5 atom%
      for the as-prepared N-GNRs. This, together with the high Brunauer-Emmett-Teller
      (BET) surface area of about 751 cm(2) g(-1), prompted us to use the N-GNR as the
      first low-cost, metal-free counter electrode for disulfide/thiolate redox
      mediated dye-sensitized solar cells (DSSCs). Compared with the widely-used
      platinum electrode, the newly-developed N-GNR counter electrode showed a
      dramatically improved power conversion efficiency for DSSCs based on the
      thiolate/disulfide redox shuttle. The observed superior cell performance was
      attributed to the enhanced charge transfer capability and electrocatalytic
      activity induced by N-doping of the graphene nanoribbon. 

PMID- 25611158
TI  - Copper-mediated formally dehydrative biaryl coupling of azine N-oxides and
      oxazoles.
AB  - A copper-mediated formally dehydrative biaryl coupling of azine N-oxides and
      oxazoles has been developed. The C-C bond-forming process proceeds, accompanied
      by the removal of the oxygen atom from the azine core, to directly afford the
      azine-oxazole biaryl linkage. Moreover, this system requires no noble transition
      metals such as palladium and rhodium, which are common promotors in the related
      dehydrogenative couplings with the azine N-oxide. Thus, the present protocol can
      provide a unique and less expensive approach to the azine-containing
      biheteroaryls of substantial interest in pharmaceutical and medicinal chemistry. 

PMID- 25611157
TI  - Gold nanoshell-decorated silicone surfaces for the near-infrared (NIR)
      photothermal destruction of the pathogenic bacterium E. faecalis.
AB  - Catheter-related infections (CRIs) are associated with the formation of
      pathogenic biofilms on the surfaces of silicone catheters, which are ubiquitous
      in medicine. These biofilms provide protection against antimicrobial agents and
      facilitate the development of bacterial resistance to antibiotics. The
      application of photothermal agents on catheter surfaces is an innovative approach
      to overcoming biofilm-generated CRIs. Gold nanoshells (AuNSs) represent a
      promising photothermal tool, because they can be used to generate heat upon
      exposure to near-infrared (NIR) radiation, are biologically inert at
      physiological temperatures, and can be engineered for the photothermal ablation
      of cells and tissue. In this study, AuNSs functionalized with carboxylate
      terminated organosulfur ligands were attached to model catheter surfaces and
      tested for their effectiveness at killing adhered Enterococcus faecalis (E.
      faecalis) bacteria. The morphology of the AuNSs was characterized by scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM), while the
      elemental composition was characterized by energy-dispersive X-ray spectroscopy
      (EDX) and X-ray photoelectron spectroscopy (XPS). Furthermore, optical and
      photothermal properties were acquired by ultraviolet-visible (UV-vis)
      spectroscopy and thermographic imaging with an infrared camera, respectively.
      Bacterial survival studies on AuNS-modified surfaces irradiated with and without
      NIR light were evaluated using a colony-formation assay. These studies
      demonstrated that AuNS-modified surfaces, when illuminated with NIR light, can
      effectively kill E. faecalis on silicone surfaces. 

PMID- 25611159
TI  - FTIR and synchronous fluorescence heterospectral two-dimensional correlation
      analyses on the binding characteristics of copper onto dissolved organic matter.
AB  - Dissolved organic matter (DOM) is known to form strong complexes with heavy
      metals and thus governs the distribution, toxicity, bioavailability, and ultimate
      fate of heavy metals in the environment. The relevant aspects of metal-organic
      interactions remain unclear because the metal binding functionalities in DOM are
      substantially nonuniform and the availability of the models is limited. In this
      work, two-dimensional correlation spectroscopy (2DCOS) integrated with
      synchronous fluorescence and infrared absorption spectroscopy was used to explore
      the binding process of copper to DOM. A series of heterogeneous binding sites in
      humic acid (HA), a representative DOM, and the subsequent subtle changes of these
      sites within the molecular interactions were elucidated by the 2DCOS method. The
      band assignments and the correspondence between the results obtained by two
      spectral probes (synchronous fluorescence and infrared absorption spectra) were
      verified by hetero-2DCOS. Our results showed that, during the copper binding
      process, the carboxyl and polysaccharide groups gave the fastest responses to
      copper binding. Then fluorescence quenching of fluorescent humic-like moieties
      occurred with a vibrational change of the related functionalities, i.e., phenolic
      and aryl carboxylic groups, which further induces the fluorescence quenching of
      fulvic-like fractions. Finally, small amounts of amide and aliphatic groups
      participated in the copper binding after the fluorescence of the protein-like
      fraction decreased. With these promising results, a comprehensive picture of
      structural changes of HA during the copper binding process was developed,
      highlighting the superior potential of 2D heterospectral correlation spectroscopy
      in studying complex interactions in the environment. 

PMID- 25611160
TI  - Understanding the binding of inhibitors of matrix metalloproteinases by molecular
      docking, quantum mechanical calculations, molecular dynamics simulations, and a
      MMGBSA/MMBappl study.
AB  - Matrix metalloproteinases (MMPs) consist of a class of proteins required for
      normal tissue function. Their over expression is associated with many disease
      states and hence the interest in MMPs as drug targets. Almost all MMP inhibitors
      have been reported to fail in clinical trials due to lack of specificity. Zinc in
      the binding site of metalloproteinases performs essential biological functions
      and contributes to the binding affinity of inhibitors. The multiple possibilities
      for coordination geometry and the consequent charge on the zinc atom indicate
      that parameters developed are not directly transferable across different families
      of zinc metalloproteinases with different zinc coordination geometries, active
      sites and ligand architectures which makes it difficult to evaluate metal-ligand
      interactions. In order to assist in drug design endeavors for MMP targets, a
      computationally tractable pathway is presented, comprising docking of small
      molecule inhibitors against the target MMPs, derivation of quantum mechanical
      charges on the zinc ion in the active site and the amino acids coordinating with
      zinc including the inhibitor molecule, molecular dynamics simulations on the
      docked ligand-MMP complexes and evaluation of binding affinities of the ligand
      MMP complexes via an accurate scoring function for zinc containing metalloprotein
      ligand complexes. The above pathway was applied to study the interaction of
      inhibitor Batimastat with MMPs, which resulted in a high correlation between the
      predicted binding free energies and experiment, suggesting the potential
      applicability of the pathway. We then proceeded to formulate a few design
      principles which identify the key protein residues for generating molecules with
      high affinity and specificity against each of the MMPs. 

PMID- 25611161
TI  - Novel insights into nickel import in Staphylococcus aureus: the positive role of
      free histidine and structural characterization of a new thiazolidine-type nickel
      chelator.
AB  - Staphylococcus aureus possesses two canonical ABC-importers dedicated to nickel
      acquisition: the NikABCDE and the CntABCDF systems, active under different growth
      conditions. This study reports on the extracytoplasmic nickel-binding components
      SaNikA and SaCntA. We showed by protein crystallography that SaNikA is able to
      bind either a Ni-(l-His)2 complex or a Ni-(l-His) (2-methyl-thiazolidine
      dicarboxylate) complex, depending on their availability in culture supernatants.
      Native mass spectrometry experiments on SaCntA revealed that it binds the Ni(ii)
      ion via a different histidine-dependent chelator but it cannot bind Ni-(l-His)2.
      In vitro experiments are consistent with in vivo nickel content measurements that
      showed that l-histidine has a high positive impact on nickel import via the Cnt
      system. These results suggest that although both systems may require free
      histidine, they use different strategies to import nickel. 

PMID- 25611162
TI  - Need and value of case management in multidisciplinary ALS care: A qualitative
      study on the perspectives of patients, spousal caregivers and professionals.
AB  - Our objective was to explore the needs and value of case management according to
      patients with amyotrophic lateral sclerosis (ALS), their spousal caregivers, and
      health care professionals in the context of multidisciplinary ALS care. We
      undertook semi-structured interviews with 10 patients with ALS, their caregivers
      (n = 10) and their ALS health care professionals (n = 10), and held a focus group
      (n = 20). We transcribed the audio-taped interviews and analysed all data
      thematically. Participants indicated that in certain circumstances case
      management can have an added value. They identified factors for receptiveness to
      case management: adequacy of usual care, rate of disease progression, and degree
      of social network support and personal factors of patients and spousal
      caregivers. Participants valued the time for consultation, house calls and
      proactive approach of the case manager. Patients with ALS and caregivers
      appreciated emotional support, whereas professionals did not mention the
      importance of emotional support by the case manager. In conclusion, ALS teams can
      consider implementation of valued aspects of case management (accessibility,
      ample time, proactive approach, emotional support) in the usual multidisciplinary
      ALS care. Additional support might be provided to patients with rapidly
      progressive disease course, passive coping style and small social network. 

PMID- 25611163
TI  - Unprecedented structural variations in trinuclear mixed valence Co(II/III)
      complexes: theoretical studies, pnicogen bonding interactions and catecholase
      like activities.
AB  - Three new mixed valence trinuclear Co(II/III) compounds cis
      [Co3L2(MeOH)2(N3)2(MU1,1-N3)2] (1), trans-[Co3L2(H2O)2(N3)2(MU1,1-N3)2].(H2O)2
      (2) and [Co3L(R)2(N3)3(MU1,3-N3)] (3) have been synthesized by reacting a di
      Schiff base ligand (H2L) or its reduced form [H2LR] (where H2L= N,N'
      bis(salicylidene)-1,3-propanediamine and H2LR= N,N'-bis(2-hydroxybenzyl)-1,3
      propanediamine) with cobalt perchlorate hexahydrate and sodium azide. All three
      products have been characterized by IR, UV-Vis and EPR spectroscopies, ESI-MS,
      elemental, powder and single crystal X-ray diffraction analyses. Complex 2 is an
      angular trinuclear species in which two terminal octahedral Co(III)N2O4 centers
      coordinate to the central octahedral cobalt(II) ion through MU2-phenoxido oxygen
      and MU1,1-azido nitrogen atoms along with two mutually cis-oxygen atoms of
      methanol molecules. On the other hand, in linear trinuclear complex , in addition
      to the MU2-phenoxido and MU1,1-azido bridges with terminal octahedral Co(III)
      centres, the central Co(II) is bonded with two mutually trans-oxygen atoms of
      water molecules. Thus the cis-trans configuration of the central Co(II) is
      solvent dependent. In complex 3, the two terminal octahedral Co(III)N2O4 centers
      coordinate to the central penta-coordinated Co(II) ion through double phenoxido
      bridges along with the nitrogen atom of a terminal azido ligand. In addition, the
      two terminal Co(III) are connected through a MU1,3-azido bridge that participates
      in pnicogen bonding interactions (intermolecular N-N interaction) as an acceptor.
      Both the cis and trans isomeric forms of 1 and 2 have been optimized using
      density functional theory (DFT) calculations and it is found that the cis
      configuration is energetically more favorable than the trans one. However, the
      trans configuration of 2 is stabilized by the hydrogen bonding network involving
      a water dimer. The pnicogen bonding interactions have been demonstrated using MEP
      surfaces and CSD search which support the counter intuitive electron acceptor
      ability of the MU1,3-azido ligand. Complexes 1-3 exhibit catecholase-like
      activities in the aerial oxidation of 3,5-di-tert-butylcatechol to the
      corresponding o-quinone. Kinetic data analyses of this oxidation reaction in
      acetonitrile reveal that the catecholase-like activity follows the order: 1 (kcat
      = 142 h(-1)) > 3 (kcat = 99 h(-1)) > 2 (kcat = 85 h(-1)). Mechanistic
      investigations of the catalytic behaviors by X-band EPR spectroscopy and
      estimation of hydrogen peroxide formation indicate that the oxidation reaction
      proceeds through the reduction of Co(III) to Co(II).

PMID- 25611165
TI  - A slow, continuous beam of cold benzonitrile.
AB  - A cold, continuous, high flux beam of benzonitrile has been created via buffer
      gas cooling. The beam has a typical forward velocity of 67 +/- 5 m s(-1), a
      velocity spread of +/-30 m s(-1) and a typical flux of 10(15) molecules s(-1),
      measured via microwave spectroscopy. This beam represents the slowest
      demonstrated forward velocity for any cold beam of medium sized (>5 atoms)
      polyatomic molecules produced to date, demonstrating a new source for high
      resolution spectroscopy. The expected resolution of a spectrometer based on such
      beams exceeds current instrument-limited resolution by almost an order of
      magnitude. This source also provides an attractive starting point for further
      spatial manipulation of such molecules, including eventual trapping. 

PMID- 25611164
TI  - Intrathecal injection of lentivirus-mediated glial cell line-derived neurotrophic
      factor RNA interference relieves bone cancer-induced pain in rats.
AB  - Bone cancer pain is a common symptom in cancer patients with bone metastases and
      the underlying mechanisms are largely unknown. The aim of this study is to
      explore the endogenous analgesic mechanisms to develop new therapeutic strategies
      for bone-cancer induced pain (BCIP) as a result of metastases. MRMT-1 tumor cells
      were injected into bilateral tibia of rats and X-rays showed that the area
      suffered from bone destruction, accompanied by an increase in osteoclast numbers.
      In addition, rats with bone cancer showed apparent mechanical and thermal
      hyperalgesia at day 28 after intratibial MRMT-1 inoculation. However, intrathecal
      injection of morphine or lentivirus-mediated glial cell line-derived neurotrophic
      factor RNAi (Lvs-siGDNF) significantly attenuated mechanical and thermal
      hyperalgesia, as shown by increases in paw withdrawal thresholds and tail-flick
      latencies, respectively. Furthermore, Lvs-siGDNF interference not only
      substantially downregulated GDNF protein levels, but also reduced substance P
      immunoreactivity and downregulated the ratio of pERK/ERK, where its activation is
      crucial for pain signaling, in the spinal dorsal horn of this model of bone
      cancer induced pain. In this study, Lvs-siGDNF gene therapy appeared to be a
      beneficial method for the treatment of bone cancer pain. As the effect of Lvs
      siGDNF to relieve pain was similar to morphine, but it is not a narcotic, the use
      of GDNF RNA interference may be considered as a new therapeutic strategy for the
      treatment of bone cancer pain in the future. 

PMID- 25611166
TI  - Corneal hysteresis and its relevance to glaucoma.
AB  - PURPOSE OF REVIEW: Glaucoma is a leading cause of irreversible blindness
      worldwide. It is estimated that roughly 60.5 million people had glaucoma in 2010
      and that this number is increasing. Many patients continue to lose vision despite
      apparent disease control according to traditional risk factors. The purpose of
      this review is to discuss the recent findings with regard to corneal hysteresis,
      a variable that is thought to be associated with the risk and progression of
      glaucoma. RECENT FINDINGS: Low corneal hysteresis is associated with optic nerve
      and visual field damage in glaucoma and the risk of structural and functional
      glaucoma progression. In addition, hysteresis may enhance intraocular pressure
      (IOP) interpretation: low corneal hysteresis is associated with a larger
      magnitude of IOP reduction following various glaucoma therapies. Corneal
      hysteresis is dynamic and may increase in eyes after IOP-lowering interventions
      are implemented. SUMMARY: It is widely accepted that central corneal thickness is
      a predictive factor for the risk of glaucoma progression. Recent evidence shows
      that corneal hysteresis also provides valuable information for several aspects of
      glaucoma management. In fact, corneal hysteresis may be more strongly associated
      with glaucoma presence, risk of progression, and effectiveness of glaucoma
      treatments than central corneal thickness.

PMID- 25611167
TI  - Mechanism and management of angle closure in uveitis.
AB  - PURPOSE OF REVIEW: To summarize the multiple mechanisms responsible for angle
      closure in uveitis and to outline the management principles and treatment
      modalities. RECENT FINDINGS: Angle closure in uveitis is a heterogeneous disease
      with multiple mechanisms. Recent advances in anterior segment imaging have
      provided insights into the mechanisms of angle closure in uveitis. Uveitic eyes
      with angle closure from pupil block require surgical iridectomy with mobilization
      of the peripheral iris and viscogoniosynechiolysis of both posterior synechiae
      and peripheral anterior synechiae. Systemic conditions associated with uveitis
      can result in anterior displacement of the iris-lens diaphragm, and present as
      acute angle closure. Pupil block is not the predominant mechanism in these eyes,
      and management is primarily medical. Data are limited on the optimal treatment of
      angle closure in uveitis, and the role of glaucoma filtration surgery, cataract
      extraction, minimally invasive glaucoma surgery and newer modalities of
      cycloablation require evaluation. SUMMARY: The management of angle closure in
      uveitis should adhere to the principles of managing both uveitic glaucoma and
      angle closure. Identification of the mechanism of angle closure in uveitic eyes
      may enable treatment to be targeted at the responsible mechanism.

PMID- 25611168
TI  - Opioid prescription claims among women of reproductive age--United States, 2008
      2012.
AB  - Prescription opioid use in the United States has become widespread, and studies
      of opioid exposure in pregnancy suggest increased risk for adverse pregnancy
      outcomes, including neonatal abstinence syndrome and birth defects (e.g., neural
      tube defects, gastroschisis, and congenital heart defects). The development of
      birth defects often results from exposures during the first few weeks of
      pregnancy, which is a critical period for organ formation. Given that many
      pregnancies are not recognized until well after the first few weeks and half of
      all U.S. pregnancies are unplanned, all women who might become pregnant are at
      risk. Therefore, it is important to assess opioid medication use among all women
      of reproductive age. CDC used Truven Health's MarketScan Commercial Claims and
      Encounters and Medicaid data to estimate the number of opioid prescriptions
      dispensed by outpatient pharmacies to women aged 15-44 years. During 2008-2012,
      opioid prescription claims were consistently higher among Medicaid-enrolled women
      when compared with privately insured women (39.4% compared with 27.7%, p<0.001).
      The most frequently prescribed opioids among women in both groups were
      hydrocodone, codeine, and oxycodone. Efforts are needed to promote interventions
      to reduce opioid prescriptions among this population when safer alternative
      treatments are available. 

PMID- 25611170
TI  - Notes from the field: investigation of contacts of a health care worker who
      worked while ill with pertussis--Maryland, August-September 2014.
AB  - On September 5, 2014, the public health department of a Maryland hospital was
      notified of a case of Bordetella pertussis infection confirmed by polymerase
      chain reaction (PCR) in a staff health care worker (HCW). The HCW experienced
      onset of diarrhea and malaise (nonrespiratory symptoms atypical of the catarrhal
      phase of pertussis) on August 26. By September 2, paroxysms of coughing led the
      HCW to consult a colleague, who ordered the PCR test, prescribed a 5-day course
      of azithromycin, and advised avoidance of patient care until treatment
      completion. Contrary to the hospital's infection control policy, neither the HCW
      nor the colleague reported the presumptive diagnosis of pertussis to the
      hospital's public health department. The HCW continued to work in the outpatient
      department until the positive PCR result was received on September 5, at which
      time the hospital's public health department was first notified. The hospital
      barred the HCW from further work at the hospital while ill, and, in collaboration
      with local and state public health counterparts, began a contact investigation
      and stratified patient and HCW contacts by level of exposure. 

PMID- 25611169
TI  - Worker illness related to newly marketed pesticides--Douglas County, Washington,
      2014.
AB  - On April 10, 2014 the Washington State Department of Agriculture (WSDA) was
      notified by a local newspaper of a suspected pesticide poisoning incident in
      Douglas County involving pesticides not previously reported in the published
      literature to be associated with human illness. On that same day, WSDA notified
      the Washington State Department of Health, which investigated this incident by
      conducting a site visit, reviewing medical and applicator records, and
      interviewing affected farmworkers, pesticide applicators, and the farmworkers'
      employer. In addition, on April 11, WSDA collected swab, foliage, and clothing
      samples and tested them for residues of pyridaben, novaluron, and triflumizole.
      In this incident, all 20 farmworkers working in a cherry orchard became ill from
      off-target drift of a pesticide mixture that was being applied to a neighboring
      pear orchard. Sixteen sought medical treatment for neurologic, gastrointestinal,
      ocular, and respiratory symptoms. This event highlights the need for greater
      efforts to prevent off-target drift exposures and promote awareness about the
      toxicity of some recently marketed pesticides. Incidents such as this could be
      prevented if farm managers planning pesticide applications notify their neighbors
      of their plans. 

PMID- 25611172
TI  - Contact allergy to finished woods in furniture and furnishings: a small allergic
      contact dermatitis epidemic to western red cedar in sauna interior decoration.
AB  - BACKGROUND: Allergic contact dermatitis caused by wood dust remains uncommon and
      most cases are occupational. Contact allergy to finished wooden products is even
      more rare and only few cases of contact dermatitis to wooden furnishings and
      furniture are described. OBJECTIVE: During 2012-2014 surprisingly many patients
      with dermatitis associated to sauna baths were referred to our clinic. METHODS:
      We report three novel cases with allergic contact dermatitis to western red cedar
      due to exposure during sauna baths. RESULTS: Three cases of non-occupational
      contact dermatitis to western red cedar were confirmed by patch testing.
      CONCLUSION: Allergic contact dermatitis to interior decoration or furniture is a
      rarity, but can be induced by novel exposures, like western red cedar in sauna
      interior decoration.

PMID- 25611171
TI  - Situational Transitions and Military Nurses: A Concept Analysis Using the
      Evolutionary Method.
AB  - BACKGROUND: Situational transitions in nursing remain a significant issue for
      both new graduates and experienced nurses. Although frequently discussed in
      current nursing literature, nursing research has exclusively focused on the
      transition experience of civilian (nonmilitary) nurses. With differing role and
      practice expectations, altered practice environments, and the risk of deployment,
      the outcome of negative transition experiences for military nurses is
      significant. PURPOSE: The purpose of this analysis is to clarify the concept of
      transition, in a situational context, as it relates to military nurses by
      investigating the attributes, antecedents, and consequences. METHODS: Rodgers'
      evolutionary method served as the framework to this study. The sample included 41
      studies, published in English, between 2000 and 2013. Data were retrieved from
      the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline,
      ProQuest, Ovid, and PsycINFO databases. CONCLUSION: Antecedents of situational
      transitions include any change in work roles or work environments. Attributes of
      situational transitions include journey, disequilibrium, finding balance,
      conditional, and pervasive. Consequences of transition range from successful to
      unsuccessful. Additional research that investigates the specific needs and
      challenges unique to nurses practicing in a military environment is needed.

PMID- 25611173
TI  - Does complete plastid genome sequencing improve species discrimination and
      phylogenetic resolution in Araucaria?
AB  - Obtaining accurate phylogenies and effective species discrimination using a small
      standardized set of plastid genes is challenging in evolutionarily young
      lineages. Complete plastid genome sequencing offers an increasingly easy-to
      access source of characters that helps address this. The usefulness of this
      approach, however, depends on the extent to which plastid haplotypes track
      morphological species boundaries. We have tested the power of complete plastid
      genomes to discriminate among multiple accessions of 11 of 13 New Caledonian
      Araucaria species, an evolutionarily young lineage where the standard DNA
      barcoding approach has so far failed and phylogenetic relationships have remained
      elusive. Additionally, 11 nuclear gene regions were Sanger sequenced for all
      accessions to ascertain the success of species discrimination using a moderate
      number of nuclear genes. Overall, fewer than half of the New Caledonian Araucaria
      species with multiple accessions were monophyletic in the plastid or nuclear
      trees. However, the plastid data retrieved a phylogeny with a higher resolution
      compared to any previously published tree of this clade and supported the
      monophyly of about twice as many species and nodes compared to the nuclear data
      set. Modest gains in discrimination thus are possible, but using complete plastid
      genomes or a small number of nuclear genes in DNA barcoding may not substantially
      raise species discriminatory power in many evolutionarily young lineages. The big
      challenge therefore remains to develop techniques that allow routine access to
      large numbers of nuclear markers scaleable to thousands of individuals from
      phylogenetically disparate sample sets. 

PMID- 25611174
TI  - Antithrombin or thrombomodulin administration in severe pneumonia patients with
      sepsis and disseminated intravascular coagulation: comment on two papers.

PMID- 25611175
TI  - Hepatitis B viral load predicts survival in hepatocellular carcinoma patients
      treated with sorafenib.
AB  - BACKGROUND AND AIM: Sorafenib is now considered as a standard treatment for
      advanced hepatocellular carcinoma (HCC). We evaluated the effect of hepatitis B
      virus (HBV) DNA titers on prognosis in HCC patients treated with sorafenib.
      METHODS: From 2008 to 2012, 78 HBV-related HCC patients who received sorafenib
      treatment at Severance Hospital were included in our analysis. The effect of
      pretreatment HBV-DNA levels on clinical outcomes for use in predicting prognosis
      after treatment with sorafenib was examined by univariate and multivariate
      analysis. RESULTS: Median overall survival and median progression-free survival
      were 5.2 months (95% confidence interval: 4.0-6.4) and 3.5 months (95% confidence
      interval: 2.3-4.7), respectively. Multivariate analysis revealed high levels of
      HBV-DNA (> 2000 IU/mL) to be an independent risk factor for worse overall
      survival (P=0.005; hazard ratio, 2.85) and disease progression among patients who
      did not receive concomitant prophylactic antiviral therapy during sorafenib
      treatment (P=0.008; hazard ratio, 87.4). Moreover, viral reactivation occurred
      more frequently in patients who did not receive concomitant prophylactic
      antiviral therapy than in those who did (4/38 vs 0/40; P=0.025). CONCLUSION:
      Higher HBV-DNA levels prior to sorafenib treatment were associated with poorer
      prognosis and increased viral reactivation thereafter. These results suggest the
      potential usefulness of prophylactic antiviral therapy when treating HBV-related
      HCC patients with sorafenib.

PMID- 25611176
TI  - The impact of relationship dynamics on the detection and reporting of elder abuse
      occurring in domestic settings.
AB  - There is a keen desire to increase the detection and reporting of elder abuse.
      The purpose of this study was to describe the circumstances under which abuse is
      detected and reported and to identify the relationship dynamics that might be
      impacting detection and reporting decisions. Interviews were conducted with 71
      Adult Protective Services (APS) caseworkers, 55 of their elderly clients, and 32
      third-party adults. Detection and reporting are distinct but related acts. The
      temporal relationship between detection and reporting generally differed
      depending on the nature and quality of the relationship between (a) the victim
      and offender and (b) the victim and reporter. Efforts to increase reporting may
      benefit from taking into consideration these relationship dynamics. A range of
      individuals detected and reported elder abuse, including victims, under a range
      of circumstances, reinforcing the value of public efforts to increase awareness
      of elder abuse. 

PMID- 25611177
TI  - Legislating interprofessional collaboration: A policy analysis of health
      professions regulatory legislation in Ontario, Canada.
AB  - Changes to Ontario's health professions regulatory system were initiated through
      various legislative amendments. These amendments introduced a legislative
      obligation for health regulatory colleges to support interprofessional
      collaboration (IPC), collaborate where they share controlled acts, and
      incorporate IPC into their quality assurance programs. The purpose of this policy
      analysis was to identify activities, strategies, and collaborations taking place
      within health professions regulatory colleges pertaining to legislative changes
      related to IPC. A qualitative content analysis of (1) college documents
      pertaining to IPC (n = 355) and (2) interviews with representatives from 14
      colleges. Three themes were identified: ideal versus reality; barriers to the
      ideal; and legislating IPC. Commitment to the ideal of IPC was evident in college
      documents and interviews. Colleges expressed concern about the lack of clarity
      regarding the intent of legislation. In addition, barriers stemming from long
      standing issues in practice including scope of practice protection, conflicting
      legislation, and lack of knowledge about the roles of other health professionals
      impede IPC. Government legislation and health professional regulation have
      important roles in supporting IPC; however, broader collaboration may be required
      to achieve policy objectives. 

PMID- 25611178
TI  - Making a Difference in Migrant Summer School: Testing a Healthy Weight
      Intervention.
AB  - OBJECTIVE: Evaluate the effectiveness of a healthy weight intervention designed
      for children of migrant farmworkers embedded in a 7-week summer Midwest Migrant
      Education Program (MEP) for changes in: weight; Body Mass Index (BMI); BMI
      percentiles (BMI-p); muscle strength and muscle flexibility; nutrition knowledge;
      attitudes; and behaviors. DESIGN AND SAMPLE: This is a two-group pre-post quasi
      experimental study. Latino children of migrant farmworkers attending summer MEP
      in grades one through eight were enrolled (n = 171: comparison n = 33,
      intervention n = 138). MEASURES: Weight, BMI, BMI-p, muscle strength and
      flexibility, knowledge, and healthy behaviors. INTERVENTION: Classroom content
      included: food variety; increasing fruits and vegetables; healthy breakfasts;
      more family meals; increasing family time; decreasing TV and electronic game
      time; increasing physical activity; limiting sugar-sweetened drinks; portion
      sizes; and food labels. RESULTS: Statistically significant were increase in
      comparison group mean weight, decrease in intervention group BMI-p, and
      improvements in muscle flexibility and healthy behavior attitudes. The
      intervention students showed trends toward healthy BMI. The number of MEP days
      attended was significantly correlated in four outcomes. CONCLUSION: Study
      findings have the potential to decrease incidence of unhealthy weight in Latino
      migrant children, reduce rates of premature adult diseases in these children, and
      a potential to decrease future health care costs.

PMID- 25611179
TI  - Prognostic impact of lymph node metastasis in distal cholangiocarcinoma.
AB  - BACKGROUND: The aim of the study was to investigate the prognostic impact of
      lymph node metastasis in cholangiocarcinoma using three different
      classifications. METHODS: Patients who underwent pancreaticoduodenectomy for
      distal cholangiocarcinoma in 24 hospitals in Japan between 2001 and 2010 were
      included. Survival was calculated by means of the Kaplan-Meier method and
      differences between subgroups were assessed with the log rank test. The Cox
      proportional hazards model was used to identify independent predictors of
      survival. chi(2) scores were calculated to determine the cut-off value of the
      number of involved nodes, lymph node ratio (LNR) and total lymph node count
      (TLNC) for discriminating survival. RESULTS: Some 370 patients were included. The
      median (range) TLNC was 19 (3-59). Nodal metastasis occurred in 157 patients
      (42.4 per cent); the median (range) number of involved nodes and LNR were 2 (1
      19) and 0.11 (0.02-0.80) respectively. Four or more involved nodes was associated
      with a significantly shorter median survival (1.3 versus 2.2 years; P = 0.001),
      as was a LNR of at least 0.17 (1.4 versus 2.3 years; P = 0.002). Involvement of
      nodes along the common hepatic artery, present in 21 patients (13.4 per cent),
      was also associated with a shorter survival (median 1.3 versus 2.1 years; P =
      0.046). Multivariable analysis among 157 node-positive patients identified the
      number of involved nodes as an independent prognostic factor (risk ratio 1.87; P
      = 0.002). CONCLUSION: The number of involved nodes was a strong predictor of
      survival in patients with distal cholangiocarcinoma.

PMID- 25611181
TI  - Traceable Self-Assembly of Laser-Triggered Cyanine-Based Micelle for Synergistic
      Therapeutic Effect.
AB  - To track nanocarriers, many researches adopt nanocarriers labeled with
      radiotracers or encapsulating near-infrared fluorescence (NIRF) dye. In this
      study, novel amphiphilic copolymers, methoxy poly(ethylene glycol) (mPEG)-cyanine
      poly(epsilon-caprolactone) (PCL) (mPEG-Cy-PCL) are synthesized. mPEG-Cy-PCL are
      capable of performing NIRF imaging, photothermal therapy (PTT) on cancer cells
      and self-assembly nanocarriers. Cy-based micelles can encapsulate doxorubicin
      (Doxo@Cy-micelle) and achieve NIRF image-guided drug delivery. Doxo@Cy-micelles
      are nanosized micelles enhancing the accumulation of Doxo in tumor sites and
      decreasing side effects. Doxo@Cy-micelles exhibit an excellent PTT and
      synergistic chemotherapy of cancer via laser-triggered release of Doxo from
      micelles, eventually resulting in decreased cancer recurrence rates. The results
      show that Cy-based micelles are excellent nanocarriers for NIRF imaging and
      synergistic photothermal-chemotherapy of cancer. 

PMID- 25611182
TI  - The transient dermal exposure II: post-exposure absorption and evaporation of
      volatile compounds.
AB  - The transient dermal exposure is one where the skin is exposed to chemical for a
      finite duration, after which the chemical is removed and no residue remains on
      the skin's surface. Chemical within the skin at the end of the exposure period
      can still enter the systemic circulation. If it has some volatility, a portion of
      it will evaporate from the surface before it has a chance to be absorbed by the
      body. The fate of this post-exposure "skin depot" is the focus of this
      theoretical study. Laplace domain solutions for concentration distribution, flux,
      and cumulative mass absorption and evaporation are presented, and time domain
      results are obtained through numerical inversion. The Final Value Theorem is
      applied to obtain the analytical solutions for the total fractional absorption by
      the body and evaporation from skin at infinite time following a transient
      exposure. The solutions depend on two dimensionless variables: chi, the ratio of
      evaporation rate to steady-state dermal permeation rate; and the ratio of
      exposure time to membrane lag time. Simple closed form algebraic equations are
      presented that closely approximate the complete analytical solutions.
      Applications of the theory to the dermal risk assessment of pharmaceutical,
      occupational, and environmental exposures are presented for four example
      chemicals.

PMID- 25611180
TI  - Cystic fibrosis-related oxidative stress and intestinal lipid disorders.
AB  - SIGNIFICANCE: Cystic fibrosis (CF) is the most common lethal genetic disorder in
      the Caucasian people. It is due to the mutation of cystic fibrosis transmembrane
      conductance regulator (CFTR) gene located on the long arm of the chromosome 7,
      which encodes for CFTR protein. The latter, an adenosine triphosphate binding
      cassette, is a transmembrane chloride channel that is also involved in
      glutathione transport. As glutathione/glutathione disulfide constitutes the most
      important pool of cellular redox systems, CFTR defects could thus disrupt the
      intracellular redox balance. Resulting multisystemic diseases are essentially
      characterized by a chronic respiratory failure, a pancreatic insufficiency, an
      essential fatty acid deficiency (EFAD), and inadequate levels of antioxidant
      vitamins. RECENT ADVANCES: The pathophysiology of CF is complex; however, several
      mechanisms are proposed, including oxidative stress (OxS) whose implication is
      recognized and has been clearly demonstrated in CF airways. CRITICAL ISSUES:
      Little is known about OxS intrinsic triggers and its own involvement in
      intestinal lipid disorders. Despite the regular administration of pancreatic
      supplements, high-fat high-calorie diets, and antioxidant fat-soluble vitamins,
      there is a persistence of steatorrhea, EFAD, and harmful OxS. Intriguingly,
      several trials with elevated doses of antioxidant vitamins have not yielded
      significant improvements. FUTURE DIRECTIONS: The main sources and self
      maintenance of OxS in CF should be clarified to improve treatment of patients.
      Therefore, this review will discuss the potential sources and study the
      mechanisms of OxS in the intestine, known to develop various complications, and
      its involvement in intestinal lipid disorders in CF patients.

PMID- 25611183
TI  - Autologous Serum Eye Drops Accelerate Epithelial Healing After LASEK.
AB  - PURPOSE: To evaluate the effect of autologous serum on the rate of epithelial
      healing and clinical results after laser epithelial keratectomy (LASEK) for
      correction of myopia. MATERIALS AND METHODS: Thirty eyes of 15 patients received
      autologous serum drops (Study Group) while 30 eyes of 15 patients received
      conventional artificial tears (Control Group) after LASEK. LASEK was performed
      with 25-second application of 18% alcohol. Laser ablation was performed with the
      ESIRIS excimer laser (SCHWIND, Kleinostheim, Germany). Patients were seen daily
      until epithelial closure, and at 1, 3, 6, and 12 months. Time to epithelial
      healing was the main outcome measure. Uncorrected visual acuity (UCVA), manifest
      refraction, and haze were recorded. RESULTS: Preoperative myopic spherical
      equivalent refraction was -2.98 +/- 1.13 diopters (D) in the study group and 
      2.65 +/- 1.01 D in the control group (p = 0.264). The mean time to epithelial
      healing was about 1 day shorter in the eyes receiving autologous serum than the
      eyes receiving conventional treatment (2.78 +/- 0.40 days versus 3.73 +/- 0.58
      days, respectively) (p = 0.001). All eyes achieved 20/25 or better UCVA at 6
      months. Over 90% of eyes were within +/-0.50 D of emmetropia at 12 months in both
      groups. No significant difference was noted in the incidence of haze.
      CONCLUSIONS: Autologous serum eye drops seem to accelerate epithelial healing
      after LASEK, which may shorten the duration of early postoperative discomfort by
      about 1 day.

PMID- 25611185
TI  - Long-lasting complete remission after therapy with temozolomide in two patients
      with macrocorticotropinoma causing Cushing's disease.

PMID- 25611184
TI  - Yo-Yo Intermittent Endurance Test-Level 1 to monitor changes in aerobic fitness
      in pre-pubertal boys.
AB  - The present study aimed to examine the performance and heart rate responses
      during the Yo-Yo Intermittent Endurance Test-Level 1 (Yo-Yo IE1) in children
      under the age of 10. One hundred and seven male children (7-9 years) performed
      the Yo-Yo IE1 at the beginning (M1), middle (M2) and end (M3) of the school year.
      Data from individual heart rate curves of the Yo-Yo IE1 were analysed in order to
      detect the inflection point between an initial phase of fast rise in heart rate
      values and a second phase in which the rise of the heart rate values is much
      smaller. The distance covered in the Yo-Yo IE1 improved from M1 to M3 (884 +/-
      496 vs. 1032 +/- 596 m; p < 0.05; d = 0.27), with intermediate values for M2 (962
      +/- 528 m). Peak heart rate (HRpeak) decreased from M1 to M2 and M3 (204 +/- 9,
      202 +/- 9 and 200 +/- 9 bpm, respectively; p < 0.05; d = 0.25-0.42). The 7th
      shuttle of the test (280 m), corresponding to 2.5 min, was identified as the
      inflection point between the two phases. Also, absolute heart rate at the 7th
      shuttle decreased progressively throughout the year (185 +/- 9, 183 +/- 10, and
      179 +/- 10 bpm; p < 0.05; d = 0.31-0.61). The present study provides evidence of
      the usefulness of a maximal as well as a submaximal version of Yo-Yo IE1 as a
      tool to monitor changes in aerobic fitness in pre-pubertal children. 

PMID- 25611187
TI  - Female Baltic herring Clupea harengus allocate resources from growth to
      reproduction in poor feeding conditions.
AB  - The trade-off between somatic growth and reproduction in the female Baltic
      herring Clupea harengus was investigated from 1984 to 2002. During the study
      period, growth decreased, as a consequence of decreasing salinity and weakening
      of feeding conditions. Production of muscle and ovarian tissue decreased in
      repeat spawners, but investment in reproduction took an increasing amount of the
      total production of new tissues. This suggested that a shift in allocation to
      reproduction takes precedence over body growth in the reproductive strategy of C.
      harengus. The process also indicated one possible mechanism leading to dwarf
      forms in fish populations.

PMID- 25611186
TI  - Effects of trypsinization and mineralization on intrasynovial tendon allograft
      healing to bone.
AB  - The purpose of the current study was to develop a novel technology to enhance
      tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an
      intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor
      digitorum profundus (FDP) tendons were used to optimize the trypsinization
      process. An additional 24 FDP tendons were stratified into control and TM groups;
      in each group, 4 tendons were used for in vitro evaluation of TM and 8 were
      transplanted into proximal tibial bone tunnels in rabbits. The samples were
      evaluated histologically and with mechanical testing at postoperative week 8.
      Maximum failure strength and linear stiffness were not significantly different
      between the control and TM tendons. A thin fibrous band of scar tissue formed at
      the graft-to-bone interface in the control group. However, only the TM group
      showed obvious new bone formation inside the tendon graft and a visible
      fibrocartilage layer at the bone tunnel entrance. This study is the first to
      explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM
      showed beneficial effects on chondrogenesis, osteogenesis, and integration of the
      intrasynovial tendon graft, but mechanical strength was the same as the control
      tendons in this short-term in vivo study.

PMID- 25611188
TI  - Predicting changes in the distribution and abundance of species under
      environmental change.
AB  - Environmental changes are expected to alter both the distribution and the
      abundance of organisms. A disproportionate amount of past work has focused on
      distribution only, either documenting historical range shifts or predicting
      future occurrence patterns. However, simultaneous predictions of abundance and
      distribution across landscapes would be far more useful. To critically assess
      which approaches represent advances towards the goal of joint predictions of
      abundance and distribution, we review recent work on changing distributions and
      on effects of environmental drivers on single populations. Several methods have
      been used to predict changing distributions. Some of these can be easily modified
      to also predict abundance, but others cannot. In parallel, demographers have
      developed a much better understanding of how changing abiotic and biotic drivers
      will influence growth rate and abundance in single populations. However, this
      demographic work has rarely taken a landscape perspective and has largely ignored
      the effects of intraspecific density. We advocate a synthetic approach in which
      population models accounting for both density dependence and effects of
      environmental drivers are used to make integrated predictions of equilibrium
      abundance and distribution across entire landscapes. Such predictions would
      constitute an important step forward in assessing the ecological consequences of
      environmental changes. 

PMID- 25611189
TI  - Structure-based design of combinatorial mutagenesis libraries.
AB  - The development of protein variants with improved properties (thermostability,
      binding affinity, catalytic activity, etc.) has greatly benefited from the
      application of high-throughput screens evaluating large, diverse combinatorial
      libraries. At the same time, since only a very limited portion of sequence space
      can be experimentally constructed and tested, an attractive possibility is to use
      computational protein design to focus libraries on a productive portion of the
      space. We present a general-purpose method, called "Structure-based Optimization
      of Combinatorial Mutagenesis" (SOCoM), which can optimize arbitrarily large
      combinatorial mutagenesis libraries directly based on structural energies of
      their constituents. SOCoM chooses both positions and substitutions, employing a
      combinatorial optimization framework based on library-averaged energy potentials
      in order to avoid explicitly modeling every variant in every possible library. In
      case study applications to green fluorescent protein, beta-lactamase, and lipase
      A, SOCoM optimizes relatively small, focused libraries whose variants achieve
      energies comparable to or better than previous library design efforts, as well as
      larger libraries (previously not designable by structure-based methods) whose
      variants cover greater diversity while still maintaining substantially better
      energies than would be achieved by representative random library approaches. By
      allowing the creation of large-scale combinatorial libraries based on structural
      calculations, SOCoM promises to increase the scope of applicability of
      computational protein design and improve the hit rate of discovering beneficial
      variants. While designs presented here focus on variant stability (predicted by
      total energy), SOCoM can readily incorporate other structure-based assessments,
      such as the energy gap between alternative conformational or bound states. 

PMID- 25611191
TI  - Claudin-1 gene variants and susceptibility to hepatitis C infection in HIV-1
      infected intravenous drug users (an ANRS case-control study).
AB  - Hepatitis C virus (HCV) seroprevalence is highly diverse among human
      immunodeficiency virus-1 (HIV-1) infected patients, ranging between 10% of HIV-1
      infected homo-bisexuel men, to >92% in patients infected with HIV-1 who acquired
      HIV-1 through intravenous drug use. Thus, being HCV-free while having acquired
      HIV-1 via intravenous drug use is a rare situation. Claudin-1 is a protein
      involved in intracellular tight-junctions and has been identified as a major
      cellular co-receptor for HCV infection. Our objective was to determine whether
      Claudin-1 gene (CLDN1) mutations might be involved in natural resistance to HCV
      infection. We conducted a case-control study. All recruited patients acquired HIV
      1 infection via intravenous drug use route before 1995. The case study patients
      remained free from HCV infection (negative anti-HCV antibodies and HCV-RNA). The
      control study patients was co-infected with HCV (positive anti-HCV antibodies).
      Direct genomic sequencing of the CLDN1 gene coding region and adjacent
      intron/exons junctions was performed from peripheral blood mononuclear cells. A
      total of 138 Caucasian patients were enrolled. Twenty-two patients (cases) were
      free from HCV infection and 116 (controls) were co-infected with HCV. We found
      single nucleotide polymorphisms (SNPs) described previously with no significant
      differences in allele frequencies between cases and controls. In conclusion,
      despite being a major cellular co-receptor for HCV entry in vitro, we did not
      identify any specific substitution in CLDN1 gene coding region in our study
      patients highly exposed but resistant to HCV infection in vivo. Other cellular co
      factors involved in HCV infection should be investigated in this highly-exposed
      intravenous drug users patients.

PMID- 25611190
TI  - Randomized clinical trial of peritoneal lavage for preventing surgical site
      infection in elective liver surgery.
AB  - BACKGROUND: Although intraoperative peritoneal lavage is often performed
      routinely with the aim of reducing peritoneal contamination, little evidence of
      lavage benefits in elective liver resection without bile duct resection is
      available. We addressed the issue with a randomized clinical trial. METHODS: We
      prospectively and randomly assigned consecutive patients undergoing liver
      resection to a lavage group or a non-lavage group. Peritoneal lavage was
      performed at the end of operation for patients in the lavage group. The primary
      endpoint was the rate of surgical site infection. RESULTS: Ninety-six patients
      were assigned to the lavage group and 97 to the non-lavage group. When
      superficial/deep incisional infection and organ/space infection were considered
      together, no significant difference in surgical site infection rate was evident
      between lavage (21.9%) and non-lavage groups (13.4%, P = 0.135). However,
      organ/space infection was significantly more frequent in the lavage group (16.7%)
      than the non-lavage group (7.2%, P = 0.048). Peritoneal lavage was identified as
      a risk factor for organ/space infection by multivariate analysis (relative risk,
      2.977; confidence interval, 1.094 to 8.100; P = 0.033). CONCLUSION:
      Intraoperative peritoneal lavage does not reduce overall incidence of surgical
      site infection and may increase risk of organ/space infection.

PMID- 25611192
TI  - QTc prolongation in schizophrenia patients in Asia: clinical correlates and
      trends between 2004 and 2008/2009.
AB  - OBJECTIVE: Little is known about the pattern of QT interval (QTc) prolongation in
      Asian patients with schizophrenia. This study examined trends of QTc prolongation
      in schizophrenia inpatients in six Asian countries and territories between 2004
      and 2008/2009 and its independent demographic and clinical correlates. METHOD:
      Data on 3482 hospitalized schizophrenia patients (2004 = 1826 and 2008/2009 =
      1656) in six Asian countries and territories were collected by either chart
      review or interviews during a 1-month period. Patients' sociodemographic and
      clinical characteristics, prescriptions of psychotropic drugs, and QTc interval
      were recorded using a standardized protocol and data collection procedure.
      RESULTS: The frequency of QTc prolongation (>456 ms) was 2.4% in the whole
      sample, decreasing from 3.1% in 2004 to 1.6% in 2008/2009 (p = 0.004) with wide
      intercountry variations. However, this decreased trend was driven by decreased
      QTc prolongation detected in China and Hong Kong (both p-values < 0.05). Multiple
      logistic regression analysis of the whole sample revealed that patients having
      more likely to have an illness lasting longer than 5 years and received
      antipsychotics classified as list-1 drugs according to the Arizona Centre for
      Education and Research on Therapeutics. Compared with 2004, patients in 2008/2009
      were less likely to have QTc prolongation. Thioridazine caused QTc prolongation
      most frequently (odds ratio (OR) 4.4; 95% confidence interval (CI) 1.2-15.2),
      followed by sulpiride (OR 2.4; 95% CI 1.3-4.5), clozapine (OR 2.4; 95% CI 1.4
      4.2), and chlorpromazine (OR 1.9; 95% CI 1.07-3.5). CONCLUSIONS: Frequency of QTc
      prolongation was low in Asian patients with schizophrenia. QTc prolongation in
      schizophrenia decreased in China and Hong Kong between 2004 and 2008/2009 but
      increased in Taiwan over the same period, remaining low in the other countries.

PMID- 25611194
TI  - A highly sensitive method for the quantification of fludrocortisone in human
      plasma using ultra-high-performance liquid chromatography tandem mass
      spectrometry and its pharmacokinetic application.
AB  - A simple and high sensitive ultra-high-performance liquid chromatography tandem
      mass spectrometry method for the determination of fludrocortisone in human plasma
      was developed and validated as per guidelines. The analyte and internal standard
      (IS), fludrocortisone-d5 , were extracted from human plasma via liquid-liquid
      extraction using tert-butyl methyl ether. The chromatographic separation was
      achieved on a Chromolith RP18e column using a mixture of acetonitrile and 2 mm
      ammonium formate (70:30, v/v) as the mobile phase at a flow rate of 0.7 mL/min.
      Quantitation was performed on a triple quadrupole mass spectrometer employing
      electrospray ionization technique, operating in multiple reaction monitoring and
      positive ion mode. The precursors to product ion transitions monitored for
      fludrocortisone and IS were m/z 381.2 -> 343.2 and 386.2 -> 348.4, respectively.
      The assay was validated with linear range of 40-3000 pg/mL. The intra- and inter
      day precisions (relative standard deviation) were within 0.49-7.13 and 0.83
      5.87%, respectively. The proposed method was successfully applied to
      pharmacokinetic studies in humans.

PMID- 25611193
TI  - Amyloid-like assembly of the low complexity domain of yeast Nab3.
AB  - Termination of transcription of short non-coding RNAs is carried out in yeast by
      the Nab3-Nrd1-Sen1 complex. Nab3 and Nrd1 are hnRNP-like proteins that dimerize
      and bind RNA with sequence specificity. We show here that an essential region of
      Nab3 that is predicted to be prion-like based upon its sequence bias, formed
      amyloid-like filaments. A similar region from Nrd1 also assembled into filaments
      in vitro. The purified Nab3 domain formed a macroscopic gel whose lattice
      organization was observed by X-ray fiber diffraction. Filaments were resistant to
      dissociation in anionic detergent, bound the fluorescent dye thioflavin T, and
      showed a beta-sheet rich structure by circular dichroism spectroscopy, similar to
      human amyloid beta which served as a reference amyloid. A version of the Nab3
      domain with a mutation that impairs its termination function, also formed fibers
      as observed by electron microscopy. Using a protein fragment interaction assay,
      the purified Nab3 domain was seen to interact with itself in living yeast. A
      similar observation was made for full length Nab3. These results suggest that the
      Nab3 and Nrd1 RNA-binding proteins can attain a complex polymeric form and raise
      the possibility that this property is important for organizing their functional
      state during termination. These findings are congruent with recent work showing
      that RNA binding proteins with low complexity domains form a dynamic subcellular
      matrix in which RNA metabolism takes place but can also aberrantly yield
      pathological aggregated particles. 

PMID- 25611195
TI  - Human herpesvirus infections of the central nervous system: laboratory diagnosis
      based on DNA detection by nested PCR in plasma and cerebrospinal fluid samples.
AB  - Infections of the central nervous systems (CNS) present a diagnostic problem for
      which an accurate laboratory diagnosis is essential. Invasive practices, such as
      cerebral biopsy, have been replaced by obtaining a polymerase chain reaction
      (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on
      DNA extracted from plasma are noninvasive, thus avoiding all of the collateral
      effects and patient risks associated with CSF collection. This study aimed to
      determine whether plasma can replace CSF in nested PCR analysis for the detection
      of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients
      whose CSF nested PCR results were positive for CNS HHV who also had the same
      organism identified by plasma nested PCR. In this study, CSF DNA was used as the
      "gold standard," and nested PCR was performed on both types of samples. Fifty-two
      patients with symptoms of nervous system infection were submitted to CSF and
      blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF
      nested PCR-was considered an active HHV infection, whereas the occurrence of two
      or more HHVs in the same sample was considered a coinfection. HHV infections were
      positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the
      plasma, difference not significant, thus nested PCR can be performed on plasma
      instead of CSF. In conclusion, this findings suggest that plasma as a useful
      material for the diagnosis of cases where there is any difficulty to perform a
      CSF puncture.

PMID- 25611196
TI  - Investigating the neuroglial differentiation effect of neuroblastoma conditioned
      medium in human endometrial stem cells cultured on 3D nanofibrous scaffold.
AB  - Neural tissue engineering is an important area of research in the field of tissue
      engineering especially for neurodegenerative disease such as spinal cord injury.
      The differentiation capacity of human endometrial stem cells (hEnSCs) into
      neuronal cells has yet to be elucidated. Here, the major aim of the present study
      was to investigate the differentiation ability of hEnSCs cultured on polylactic
      acid/chitosan (PLA/CS) nanofibrous scaffold into neuroglial cells in response to
      conditioned medium of BE(2)-C human neuroblastoma cells and growth factors. Here
      we investigated the use PLA/CS scaffold as a three dimensional (3D) system that
      increased neuro-glial cells differentiation. Human EnSCs after three passages
      were differentiated in neuro-glial like cells under neuroblastoma conditioned
      medium with FGF2/PDGF-AA on PLA/CS scaffold. By day 18, differentiated cells were
      analyzed for expression of neuroglial markers by qRT-PCR and immunofluorescence.
      The results revealed that hEnSCs attach, grow and differentiation on the
      nanofibrous PLA/CS scaffold. Additionally, our study showed the expression of
      neural and glial lineage markers such as Nestin, NF-L, MAP2, PDGFRa, CNP, Olig2,
      MBP, and GFAP in the level of mRNA and MAP2, Tuj-1, and NF-L in the protein level
      after 18 days. Our results demonstrate that hEnSCs cultured on PLA/CS nanofibrous
      scaffold have the potential to differentiate in neuronal and glial cells in
      presence of neuroblastoma conditioned medium on PLA/CS scaffold. The result of
      this study may have impact in tissue engineering and cells-base therapy of
      neurodegenerative diseases and have a great potential for wide application.

PMID- 25611197
TI  - General and mild Ni(0)-catalyzed alpha-arylation of ketones using aryl chlorides.
AB  - A general methodology for the alpha-arylation of ketones using a nickel catalyst
      has been developed. The new well-defined [Ni(IPr*)(cin)Cl] (1 c) pre-catalyst
      showed great efficiency for this transformation, allowing the coupling of a wide
      range of ketones, including acetophenone derivatives, with various functionalised
      aryl chlorides. This cinnamyl-based Ni-N-heterocyclic carbene (NHC) complex has
      demonstrated a different behaviour to previously reported NHC-Ni catalysts.
      Preliminary mechanistic studies suggest a Ni(0)/Ni(II) catalytic cycle to be at
      play.

PMID- 25611198
TI  - Interface engineering of a CoO(x)/Ta3N5 photocatalyst for unprecedented water
      oxidation performance under visible-light-irradiation.
AB  - Cocatalysts have been extensively used to promote water oxidation efficiency in
      solar-to-chemical energy conversion, but the influence of interface compatibility
      between semiconductor and cocatalyst has been rarely addressed. Here we
      demonstrate a feasible strategy of interface wettability modification to enhance
      water oxidation efficiency of the state-of-the-art CoO(x)/Ta3N5 system. When the
      hydrophobic feature of a Ta3N5 semiconductor was modulated to a hydrophilic one
      by in situ or ex situ surface coating with a magnesia nanolayer (2-5 nm), the
      interfacial contact between the hydrophilic CoO(x) cocatalyst and the modified
      hydrophilic Ta3N5 semiconductor was greatly improved. Consequently, the visible
      light-driven photocatalytic oxygen evolution rate of the resulting CoO(x)/MgO(in)
      Ta3N5 photocatalyst is ca. 23 times that of the pristine Ta3N5 sample, with a new
      record (11.3%) of apparent quantum efficiency (AQE) under 500-600 nm
      illumination.

PMID- 25611199
TI  - Hyperspectral microscopy as an analytical tool for nanomaterials.
AB  - Hyperspectral microscopy is an advanced visualization technique that combines
      hyperspectral imaging with state-of-the-art optics and computer software to
      enable the rapid identification of materials at the micro- and nanoscales.
      Achieving this level of resolution has traditionally required time-consuming and
      costly electron microscopy techniques. While hyperspectral microscopy has already
      been applied to the analysis of bulk materials and biologicals, it shows
      extraordinary promise as an analytical tool to locate individual nanoparticles
      and aggregates in complex samples through rapid optical and spectroscopic
      identification. This technique can be used to not only screen for the presence of
      nanomaterials, but also to locate, identify, and characterize them. It could also
      be used to identify a subset of samples that would then move on for further
      analysis via other advanced metrology. This review will describe the science and
      origins of hyperspectral microscopy, examine current and emerging applications in
      life science, and examine potential applications of this technology that could
      improve research efficiency or lead to novel discoveries.

PMID- 25611200
TI  - Attitudes towards organ donor advocacy among Swedish intensive care nurses.
AB  - OBJECTIVES: To explore the attitudes of Swedish intensive care nurses towards
      organ donor advocacy. BACKGROUND: The concept of organ donor advocacy is critical
      to nurses who care for potential donors in order to facilitate organ donation
      (OD). DESIGN: A retrospective cross-sectional study was employed. METHODS:
      Inclusion criteria in this survey were to be a registered nurse and to work in a
      Swedish intensive care unit (ICU). Participants were identified by the Swedish
      association of health professionals. A number of 502 Swedish ICU nurses answered
      the 32-item questionnaire Attitudes Towards Organ Donor Advocacy Scale (ATODAS),
      covering the five dimensions of organ donor advocacy: attitudes towards
      championing organ donation at a structural hospital level, or at a political and
      research level, attitudes towards actively and personally safeguarding the will
      and wishes of the potential organ donor, or by using a more professional approach
      and finally to safeguard the will and wishes of the relatives. Data were analysed
      with the SPSS version 18.0 and the results were assessed by using Student's t
      test and post hoc test, analysis of variance (ANOVA), chi(2) , Pearson's
      correlation and regression analysis. RESULTS: The most favoured advocacy action
      was safeguarding the POD's will and wishes by a professional approach, closely
      followed by actively and personally safeguarding the POD's will and wishes.
      Nurses at local hospitals reported a more positive attitude towards organ donor
      advocacy overall compared with nurses at larger regional or university hospitals.
      Important factors leading to positive attitudes were seniority, working
      experience, participating in conversations with relatives, caring for brain-dead
      persons and private experiences from OD or organ transplantation. CONCLUSIONS:
      Intensive and critical care nurses with short working experience in university
      hospitals showed the least positive attitude towards organ donor advocacy. This
      is problematic because many ODs and all transplantations are performed in
      university hospitals. RELEVANCE TO CLINICAL PRACTICE: This study emphasizes the
      importance of organizing the care of PODs and their relatives in a way that
      promotes advocacy.

PMID- 25611201
TI  - Postgenomics biomarkers for rabies-the next decade of proteomics.
AB  - Rabies is one of the oldest diseases known to mankind. The pathogenic mechanisms
      by which rabies virus infection leads to development of neurological disease and
      death are still poorly understood. Analysis of rabies-infected proteomes may help
      identify novel biomarkers for antemortem diagnosis of the disease and target
      molecules for therapeutic intervention. This article offers a literature
      synthesis and critique of the differentially expressed proteins that have been
      previously reported from various in vitro/in vivo model systems and naturally
      infected clinical specimens. The emerging data collectively indicate that, in
      addition to the obvious alterations in proteins involved in synapse and
      neurotransmission, a majority of cytoskeletal proteins are relevant as well,
      providing evidence of neuronal degeneration. An interesting observation is that
      certain molecules, such as KPNA4, could be potential diagnostic markers for
      rabies. Importantly, proteomic studies with body fluids such as cerebrospinal
      fluid provide newer insights into antemortem diagnosis. In order to develop a
      complete integrative biology picture, it is essential to analyze the entire CNS
      (region-wise) and in particular, the brain. We suggest the use of laboratory
      animal models over cell culture systems using a combinatorial proteomics
      approach, as the former is a closer match to the actual host response. While most
      studies have focused on the terminal stages of the disease in mice, a time-series
      analysis could provide deeper insights for therapy. Postgenomics technologies
      such as proteomics warrant more extensive applications in rabies and similar
      diseases impacting public health around the world. 

PMID- 25611202
TI  - Postoperative Rehabilitation After Hip Resurfacing: A Systematic Review.
AB  - CONTEXT: Hip-resurfacing arthroplasty (HRA) has become a popular procedure in the
      treatment of hip-joint arthritis in individuals under the age of 65 y. Although
      the body of literature examining operative procedures has grown, there is a lack
      of consistent reporting of the effectiveness of an HRA postoperative
      rehabilitation program. To date, no systematic reviews have evaluated the
      available evidence on postoperative rehabilitation programs. OBJECTIVE: To
      evaluate the available evidence on postoperative rehabilitation programs after
      HRA. EVIDENCE ACQUISITION: A systematic review was conducted according to the
      PRISMA guidelines. A search of PubMed, CINAHL, SPORTDiscus, ProQuest, and Google
      Scholar was conducted in April 2014 using the following keywords alone and in
      combination: postoperative, postsurgical, rehabilitation, physical therapy,
      programs, hip resurfacing, arthroplasty, and metal-on-metal. The grading of
      studies was conducted using the PEDro and Oxford Centre for Evidence-Based
      Medicine scales. EVIDENCE SYNTHESIS: The authors identified 648 citations, 4 of
      which met the inclusion criteria. The qualifying studies yielded 1 randomized
      control trial, 2 case reports, and 1 case series, for a total of 90 patients.
      Patients were mostly male (n = 86), had a mean age of 48 +/- 5.47 y, and had been
      physically active before HRA. Postoperative rehabilitation programs varied in
      length (range 8-24 wk) and consisted of at least 3 phases. The methodology to
      assess program effects varied, but all 4 studies did measure a combination of
      function, pain, and quality of life using written questionnaires, with follow-up
      ranging from 9 mo to 1 y. The most common questionnaire was the Harris Hip Score.
      CONCLUSION: This review found postoperative rehabilitation programs after HRA to
      be underinvestigated. Limited results indicate that postoperative rehabilitation
      programs may be effective in improving gait (stride length, velocity, and
      cadence), hip range of motion, and pain and function, as measured by
      questionnaires, but not hip strength.

PMID- 25611203
TI  - Corticosteroid-induced morphological changes in cells of the myeloid lineage.

PMID- 25611205
TI  - Rotational artifacts in on-board cone beam computed tomography.
AB  - Rotational artifacts in image guidance systems lead to registration errors that
      affect non-isocentric treatments and dose to off-axis organs-at-risk. This study
      investigates a rotational artifact in the images acquired with the on-board cone
      beam computed tomography system XVI (Elekta, Stockholm, Sweden). The goals of the
      study are to identify the cause of the artifact, to characterize its dependence
      on other quantities, and to investigate possible solutions. A 30 cm diameter
      cylindrical phantom is used to acquire clockwise and counterclockwise scans at
      five speeds (120 to 360 deg min(-1)) on six Elekta linear accelerators from three
      generations (MLCi, MLCi2 and Agility). Additional scans are acquired with
      different pulse widths and focal spot sizes for the same mAs. Image quality is
      evaluated using a common phantom with an in-house three dimensional contrast
      transfer function attachment. A robust, operator-independent analysis is
      developed which quantifies rotational artifacts with 0.02 degrees  accuracy and
      imaging system delays with 3 ms accuracy. Results show that the artifact is
      caused by mislabelling of the projections with a lagging angle due to various
      imaging system delays. For the most clinically used scan speed (360 deg min(-1)),
      the artifact is ~0.5 degrees , which corresponds to ~0.25 degrees  error per scan
      direction with the standard Elekta procedure for angle calibration. This leads to
      a 0.5 mm registration error at 11 cm off-center. The artifact increases linearly
      with scan speed, indicating that the system delay is independent of scan speed.
      For the most commonly used pulse width of 40 ms, this delay is 34 +/- 1 ms, part
      of which is half the pulse width. Results are consistent among the three linac
      generations. A software solution that corrects the angles of individual
      projections is shown to eliminate the rotational error for all scan speeds and
      directions. Until such a solution is available from the manufacturer, three
      clinical solutions are presented, which reduce the rotational error without
      compromising image quality.

PMID- 25611206
TI  - The relation of preeclampsia and serum level of 25-hydroxyvitamin D in mothers
      and their neonates: a case control study in Iran.
AB  - The predisposing factors of preeclampsia may endanger the mother's heath as well
      as her neonate. One hypothesis related to preeclampsia is vitamin D deficiency or
      insufficiency. This study was conducted to evaluate the relationship between
      preeclampsia and the serum level of 25-hydroxyvitamin D (25-OH-D) in mothers and
      their neonates. In this case-control study, we recruited 41 preeclamptic and 50
      healthy women from the Imam Khomeini Hospital in Ahvaz, Iran. Venous blood (2 ml)
      from mothers (in time of labor) and 2 ml of blood from the umbilical cord were
      taken, centrifuged, stored at -30 degrees C and sent to a laboratory for analysis
      of 25-OH-D by ELISA. Vitamin D levels<20 ng/ml were regarded as deficiency,
      levels between 21-29 ng/ml were regarded as insufficiency, and if levels were
      higher than 30 ng/ml, these were considered normal. Independent t-test, chi
      square, Spearman correlation coefficient and logistic regression were used to
      analyze data. Mean levels of 25-OH-D were significantly lower in preeclamptic
      women (15.2+/-13.6 vs. 23.3+/-15.3 ng/ml, p=0.001) and in their neonates (15.2+/
      13.1 vs. 21.6+/-12.6 ng/ml, p=0.01) compared to normal pregnant women and their
      neonates. There was a significant relationship between the levels of vitamin D in
      preeclamptic women with levels of this vitamin in their neonates (r=0.901,
      p=0.0001). 25-OH-D deficiency that exist in preeclamptic mothers, may be a health
      risk for their infants, therefore, early use of vitamin D supplement with higher
      dose than 400 IU in Iranian women is recommended. 

PMID- 25611204
TI  - A probabilistic palimpsest model of visual short-term memory.
AB  - Working memory plays a key role in cognition, and yet its mechanisms remain much
      debated. Human performance on memory tasks is severely limited; however, the two
      major classes of theory explaining the limits leave open questions about key
      issues such as how multiple simultaneously-represented items can be
      distinguished. We propose a palimpsest model, with the occurrent activity of a
      single population of neurons coding for several multi-featured items. Using a
      probabilistic approach to storage and recall, we show how this model can account
      for many qualitative aspects of existing experimental data. In our account, the
      underlying nature of a memory item depends entirely on the characteristics of the
      population representation, and we provide analytical and numerical insights into
      critical issues such as multiplicity and binding. We consider representations in
      which information about individual feature values is partially separate from the
      information about binding that creates single items out of multiple features. An
      appropriate balance between these two types of information is required to capture
      fully the different types of error seen in human experimental data. Our model
      provides the first principled account of misbinding errors. We also suggest a
      specific set of stimuli designed to elucidate the representations that subjects
      actually employ. 

PMID- 25611207
TI  - Time-course of prednisone effects on hormonal and inflammatory responses at rest
      and during resistance exercise.
AB  - Glucocorticoids are among the most commonly used drugs. They are widely
      administered for acute and chronic musculoskeletal pain, as well as for several
      other pain syndromes, although their therapeutic use is sometimes diverted for
      doping purposes. Their time-course effects on hormonal and inflammatory responses
      nevertheless remain poorly understood, both at rest and during exercise. We
      therefore studied the alterations induced by 1 week of prednisone treatment (60
      mg daily) in recreationally trained male athletes after 2 days (i. e., acute) and
      7 days (i. e., short-term). Hormonal (i. e., DHEA, DHEA-S, aldosterone, and
      testosterone) and pro- and anti-inflammatory markers (i. e., IL-6, IL-10, and IL
      1beta) were investigated at rest and after resistance exercise. A significant
      decrease in DHEA and DHEA-S (p<0.01) without change in the DHEA/DHEA-S ratio,
      aldosterone, or testosterone was demonstrated after acute prednisone intake. A
      significant increment in IL-10 and a significant decrement in IL-6 (p<0.05) were
      also observed with prednisone both at rest and during exercise, without
      significant change in IL-1beta. Continued prednisone treatment led to another
      significant decrease in both DHEA and DHEA-S (p<0.05), whereas no change in the
      inflammatory markers was observed between days 2 and 7. Our data demonstrate that
      the anti-inflammatory effects of prednisone were maximal and stable from the
      beginning of treatment, both in rest and exercise conditions. However, hormonal
      concentrations continued to decline during short-term intake. Further studies are
      needed to determine the effects of hormonal time-course alterations with longer
      glucocorticoid treatment and the clinical consequences.

PMID- 25611208
TI  - Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti
      Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly
      by Suppressing AGEs-Receptor Axis.
AB  - Advanced glycation end products (AGEs) and receptor RAGE play a role in diabetic
      nephropathy. We have previously shown that increased glucose uptake into proximal
      tubular cells via sodium-glucose cotransporter 2 (SGLT2) stimulates oxidative
      stress generation and RAGE expression, thereby exacerbating the AGE-induced
      apoptosis in this cell type. However, the protective role of SGLT2 inhibition
      against the AGE-RAGE-induced renal damage in diabetic animals remains unclear. In
      this study, we investigated the effects of empagliflozin, SGLT2 inhibitor on AGE
      RAGE axis, inflammatory and fibrotic reactions, and tubular injury in the kidney
      of streptozotocin-induced diabetic rats.Administration of empagliflozin for 4
      weeks significantly improved hyperglycemia and HbA1c, and decreased expression
      levels of AGEs, RAGE, 8-hydroxydeoxyguanosine (8-OHdG), and F4/80, markers of
      oxidative stress and macrophages, respectively, in the diabetic kidney. Although
      empagliflozin did not reduce albuminuria, it significantly decreased urinary
      excretion levels of 8-OHdG and L-fatty acid binding protein, a marker of tubular
      injury. Moreover, inflammatory and fibrotic gene expression such as monocyte
      chemoattractant protein-1, intercellular adhesion molecule-1, plasminogen
      activator inhibitor-1, transforming growth factor-beta, and connective tissue
      growth factor was enhanced in the diabetic kidney, all of which were prevented by
      empagliflozin. The present study suggests that empagliflozin could inhibit
      oxidative, inflammatory and fibrotic reactions in the kidney of diabetic rats
      partly via suppression of the AGE-RAGE axis. Blockade of the increased glucose
      uptake into renal proximal tubular cells by empagliflozin might be a novel
      therapeutic target for tubulointerstitial damage in diabetic nephropathy. 

PMID- 25611209
TI  - Theoretical and thermochemical network approaches to determine the heats of
      formation for HO2 and its ionic counterparts.

PMID- 25611210
TI  - Multilocus phylogenetic and geospatial analyses illuminate diversification
      patterns and the biogeographic history of Malagasy endemic plated lizards
      (Gerrhosauridae: Zonosaurinae).
AB  - Although numerous studies have attempted to find single unifying mechanisms for
      generating Madagascar's unique flora and fauna, little consensus has been reached
      regarding the relative importance of climatic, geologic and ecological processes
      as catalysts of diversification of the region's unique biota. Rather, recent work
      has shown that both biological and physical drivers of diversification are best
      analysed in a case-by-case setting with attention focused on the ecological and
      life-history requirements of the specific phylogenetic lineage under
      investigation. Here, we utilize a comprehensive analytical approach to examine
      evolutionary drivers and elucidate the biogeographic history of Malagasy plated
      lizards (Zonosaurinae). Data from three genes are combined with fossil
      information to construct time-calibrated species trees for zonosaurines and their
      African relatives, which are used to test alternative diversification hypotheses.
      Methods are utilized for explicitly incorporating phylogenetic uncertainty into
      downstream analyses. Species distribution models are created for 14 of 19
      currently recognized species, which are then used to estimate spatial patterns of
      species richness and endemicity. Spatially explicit analyses are employed to
      correlate patterns of diversity with both topographic heterogeneity and climatic
      stability through geologic time. We then use inferred geographic ranges to
      estimate the biogeographic history of zonosaurines within each of Madagascar's
      major biomes. Results suggest constant Neogene and Quaternary speciation with
      divergence from the African most recent common ancestor ~30 million years ago
      when oceanic currents and African rivers facilitated dispersal. Spatial patterns
      of diversity appear concentrated along coastal regions of northern and southern
      Madagascar. We find no relationship between either topographic heterogeneity or
      climatic stability and patterns of diversity. Ancestral state reconstructions
      suggest that western dry forests were important centres of origin with recent
      invasion into spiny and rain forest. These data highlight the power of combining
      multilocus phylogenetic and spatially explicit analyses for testing alternative
      diversification hypotheses within Madagascar's unique biota and more generally,
      particularly as applied to phylogenetically and biologically constrained systems.

PMID- 25611211
TI  - Humoral immunocompetence shifts in response to developmental stage change and
      mating access in Bactrocera dorsalis Hendel (Diptera: Tephritidae).
AB  - Because immune defenses are often costly employed, insect immunocompetence cannot
      be always maintained at its maximum level. Here, the oriental fruit fly,
      Bactrocera dorsalis (Hendel), was used as a study object to investigate how its
      immune defenses varied with the developmental stage change and mating access. Our
      data indicated that both phenoloxidase (PO) activity and antibacterial activity
      significantly increased from new larvae to pupae but decreased in adults after
      emergence. Furthermore, both the PO activity and antibacterial activity in the
      hemolymph of copulated male and female adults were dramatically higher than that
      of virgin male and female ones, respectively. It provided the evidence that
      copulation could increase the magnitude of immune defense in hemolymph of B.
      dorsalis. Together, these results suggest that B. dorsalis possess a flexible
      investment strategy in immunity to meet its specific needs based on the endo- and
      exogenous factors, such as their distinct food source and living environments. 

PMID- 25611212
TI  - Sub-3 nm Co3O4 nanofilms with enhanced supercapacitor properties.
AB  - Two-dimensional materials often show a range of intriguing electronic, catalytic,
      and optical properties that differ greatly from conventional nanoparticles.
      Herein, we demonstrate the large-scale preparation of sub-3 nm atomic layers
      Co3O4 nanofilms with a nonsurfactant and substrate-free hydrothermal method. This
      successful preparation of ultrathin nanofilms highlighted the reconstruction of
      cobalt-ammonia complexes and synergistic effect of free ammonia and nitrate on
      film growth control. Subsequent performance tests uncovered that these sub-3 nm
      atomic layer Co3O4 nanofilms exhibited an ultrahigh specific capacitance of 1400
      F/g in the first galvanostatic charge/discharge test. The specific capacitance of
      Co3O4 nanofilms only slightly decayed less than 3% after 1500 cycling tests. With
      some parameter adjustments, similar Co(OH)2 nanofilms with a thickness of 3.70 +/
      0.10 nm were also prepared. The Co(OH)2 nanofilms possessed maximum specific
      capacitance of 1076 F/g and peak performance attenuation of about 2% after a
      cycle stability test. 

PMID- 25611213
TI  - In vivo biomechanical mapping of normal and keratoconus corneas.

PMID- 25611214
TI  - All cues are not created equal: the case for facilitating the acquisition of
      typical weighting strategies in children with hearing loss.
AB  - PURPOSE: One task of childhood involves learning to optimally weight acoustic
      cues in the speech signal in order to recover phonemic categories. This study
      examined the extent to which spectral degradation, as associated with cochlear
      implants, might interfere. The 3 goals were to measure, for adults and children,
      (a) cue weighting with spectrally degraded signals, (b) sensitivity to degraded
      cues, and (c) word recognition for degraded signals. METHOD: Twenty-three adults
      and 36 children (10 and 8 years old) labeled spectrally degraded stimuli from
      /balpha/-to-/walpha/ continua varying in formant and amplitude rise time (FRT and
      ART). They also discriminated degraded stimuli from FRT and ART continua, and
      recognized words. RESULTS: A developmental increase in the weight assigned to FRT
      in labeling was clearly observed, with a slight decrease in weight assigned to
      ART. Sensitivity to these degraded cues measured by the discrimination task could
      not explain variability in cue weighting. FRT cue weighting explained significant
      variability in word recognition; ART cue weighting did not. CONCLUSION: Spectral
      degradation affects children more than adults, but that degradation cannot
      explain the greater diminishment in children's weighting of FRT. It is suggested
      that auditory training could strengthen the weighting of spectral cues for
      implant recipients.

PMID- 25611215
TI  - Iridoid glycosides from Barleria lupulina.
AB  - Phytochemical investigation of an extract of the aerial part of Barleria lupulina
      resulted in the identification of four new iridoid glycosides (1-4), together
      with 14 known analogues (5-18). The structures of 1-4 were determined through 1D
      and 2D NMR spectroscopic data analysis, HRMS, and acid hydrolysis. This is the
      first report of iridoid glycosides with a formate group. The free-radical
      scavenging activity of compounds 9, 12, and 15-17 was assessed using the DPPH
      assay. Compounds 16 and 17 scavenged DPPH radicals weakly with IC50 values of
      97.5 and 78.6 MUg/mL, respectively. 

PMID- 25611216
TI  - Flow chemistry: intelligent processing of gas-liquid transformations using a tube
      in-tube reactor.
AB  - CONSPECTUS: The previous decade has witnessed the expeditious uptake of flow
      chemistry techniques in modern synthesis laboratories, and flow-based chemistry
      is poised to significantly impact our approach to chemical preparation. The
      advantages of moving from classical batch synthesis to flow mode, in order to
      address the limitations of traditional approaches, particularly within the
      context of organic synthesis are now well established. Flow chemistry methodology
      has led to measurable improvements in safety and reduced energy consumption and
      has enabled the expansion of available reaction conditions. Contributions from
      our own laboratories have focused on the establishment of flow chemistry methods
      to address challenges associated with the assembly of complex targets through the
      development of multistep methods employing supported reagents and in-line
      monitoring of reaction intermediates to ensure the delivery of high quality
      target compounds. Recently, flow chemistry approaches have addressed the
      challenges associated with reactions utilizing reactive gases in classical batch
      synthesis. The small volumes of microreactors ameliorate the hazards of high
      pressure gas reactions and enable improved mixing with the liquid phase.
      Established strategies for gas-liquid reactions in flow have relied on plug-flow
      (or segmented flow) regimes in which the gas plugs are introduced to a liquid
      stream and dissolution of gas relies on interfacial contact of the gas bubble
      with the liquid phase. This approach confers limited control over gas
      concentration within the liquid phase and is unsuitable for multistep methods
      requiring heterogeneous catalysis or solid supported reagents. We have identified
      the use of a gas-permeable fluoropolymer, Teflon AF-2400, as a simple method of
      achieving efficient gas-liquid contact to afford homogeneous solutions of
      reactive gases in flow. The membrane permits the transport of a wide range of
      gases with significant control of the stoichiometry of reactive gas in a given
      reaction mixture. We have developed a tube-in-tube reactor device consisting of a
      pair of concentric capillaries in which pressurized gas permeates through an
      inner Teflon AF-2400 tube and reacts with dissolved substrate within a liquid
      phase that flows within a second gas impermeable tube. This Account examines our
      efforts toward the development of a simple, unified methodology for the
      processing of gaseous reagents in flow by way of development of a tube-in-tube
      reactor device and applications to key C-C, C-N, and C-O bond forming and
      hydrogenation reactions. We further describe the application to multistep
      reactions using solid-supported reagents and extend the technology to processes
      utilizing multiple gas reagents. A key feature of our work is the development of
      computer-aided imaging techniques to allow automated in-line monitoring of gas
      concentration and stoichiometry in real time. We anticipate that this Account
      will illustrate the convenience and benefits of membrane tube-in-tube reactor
      technology to improve and concomitantly broaden the scope of gas/liquid/solid
      reactions in organic synthesis.

PMID- 25611218
TI  - On the origin of the differences in structure directing properties of polar metal
      oxyfluoride [MO(x)F(6-x)]2- (x = 1, 2) building units.
AB  - In oxyfluoride chemistry, the [MO(x)F(6-x)](2-) anions (M = transition metal) are
      interesting polar building units that may be used to design polar materials, but
      their polar vs antipolar orientations in the solid state, which directly depend
      on the interactions between O(2-)/F(-) ligands and the extended structure, remain
      difficult to control. To improve this control, these interactions were assessed
      through crystallization of five related [MO(x)F(6-x)](2-) (M = Ti(4+), V(5+),
      Mo(6+), W(6+)) anions with organic molecules. The hybrid organic-inorganic
      compounds, (4,4'-bpyH2)TiF6 (1), (enH2)MoO2F4 (2), (4-hpyH)2MoO2F4.H2O (3), (4,4'
      bpyH2)WO2F4 (4), and (4,4'-bpyH2)VOF5 (5), exhibit isolated [MO(x)F(6-x)](2-)
      anions in a hydrogen bond network. The analysis of these crystal structures in
      combination with DFT calculations elucidate how differences in structure
      directing properties of these anions arise when pi-overlap between O 2p orbitals
      and M d orbitals is weak and significantly affected by an increase of the energy
      of the d orbitals from 3d to 5d.

PMID- 25611217
TI  - Conjugation of cell-penetrating peptides to parathyroid hormone affects its
      structure, potency, and transepithelial permeation.
AB  - Delivery of therapeutic peptides and proteins by the use of cell-penetrating
      peptides (CPPs) as carriers has been suggested as a feasible strategy. The aim of
      the present study was to investigate the effect of conjugating a series of well
      known CPPs to the biologically active part of parathyroid hormone, i.e., PTH(1
      34), and to evaluate the effect with regard to secondary structure, potency in
      Saos-2 cells, immunogenicity, safety, as well as the transepithelial permeation
      across monolayers by using the Caco-2 cell culture model. Further, co
      administration of CPP and PTH(1-34) as an alternative to covalent conjugation was
      compared with regard to the transepithelial permeation. CPP-conjugated PTH(1-34)
      fusion peptides were successfully expressed in Escherichia coli and purified from
      inclusion bodies. No clear correlation between the degree of secondary structure
      of the CPP-conjugated PTH(1-34) fusion peptides and their potency was found,
      albeit a general decrease in permeation was observed for both N- and C-terminally
      CPP-conjugated PTH(1-34) as compared to native PTH(1-34). However, attachment of
      CPP to the N-terminus significantly increased permeation across Caco-2 cell
      monolayers as compared to the corresponding C-terminally CPP-conjugated PTH(1
      34). In addition, the nonaarginine sequence proved to be the only CPP capable of
      increasing permeation when conjugated to PTH(1-34) as compared to co
      administration of CPP and PTH(1-34). This enhancement effect was, however,
      associated with an unacceptably low level of cell viability. In conclusion,
      covalent conjugation of CPPs to PTH(1-34) influenced the secondary structure,
      potency, and transepithelial permeation efficiency of the resulting conjugate,
      and hence this approach appears not to be favorable as compared to co
      administration when optimizing CPP-mediated permeation of PTH(1-34) across an
      intestinal epithelium. 

PMID- 25611219
TI  - Mechanistic rationalization of unusual sigmoidal kinetic profiles in the Machetti
      De Sarlo cycloaddition reaction.
AB  - Unusual sigmoidal kinetic profiles in the Machetti-De Sarlo base-catalyzed 1,3
      dipolar cycloaddition of acrylamide to N-methylnitroacetamide are rationalized by
      detailed in situ kinetic analysis. A dual role is uncovered in which a substrate
      acts as a precursor to catalyze its own reaction. Such kinetic studies provide a
      general protocol for distinguishing among different mechanistic origins of
      induction periods in complex organic reactions. 

PMID- 25611220
TI  - An unidentified endobronchial object in a newly transplanted lung.
AB  - A fiberoptic examination is recommended at the end of lung transplantation for
      bronchial toilet and to check the bronchial anastomoses. This procedure permitted
      detection of a 10 * 4-mm piece of plastic of unknown origin in the left lingular
      bronchus and suggests that bronchoscopy should be performed before implanting the
      transplanted lung. 

PMID- 25611221
TI  - Mucosal Erosion of the Cricoid Cartilage After the Use of an i-Gel Supraglottic
      Airway Device in a Patient with Diffuse Idiopathic Skeletal Hyperostosis.
AB  - After standard hip arthroplasty, an 82-year-old patient with previously
      undiagnosed diffuse idiopathic skeletal hyperostosis of the cervical spine
      experienced life-threatening side effects after use of a supraglottic airway
      device (i-gel). Extensive mucosal erosion and denudation of the cricoid cartilage
      caused postoperative supraglottic swelling and prolonged respiratory failure
      requiring tracheostomy. In this case report, we highlight the importance of
      evaluating risk factors for failure of supraglottic airway devices. 

PMID- 25611222
TI  - Soft Palate Ulceration After Brief Use of an i-Gel Supraglottic Airway.
AB  - We describe a case of extensive soft palate ulceration after the use of an i-gel
      supraglottic airway device (Intersurgical Ltd, Wokingham, United Kingdom) during
      a knee arthroscopy in a 61-year-old man. He presented with pain and soft palate
      ulceration, which eventually required hospital admission because of dehydration.
      The pharynx healed completely within 3 months, with a change in taste as the
      remaining symptom. 

PMID- 25611225
TI  - Racial differences in lung cancer genetics.

PMID- 25611223
TI  - Editorial Comment: Mucosal Erosion of the Cricoid Cartilage After the Use of an i
      Gel Supraglottic Airway Device in a Patient with Diffuse Idiopathic Skeletal
      Hyperostosis AND Soft Palate Ulceration After Brief Use of an i-Gel Supraglottic
      Airway.

PMID- 25611226
TI  - Perspectives of novel imaging techniques for staging, therapy response
      assessment, and monitoring of surveillance in lung cancer: summary of the Dresden
      2013 Post WCLC-IASLC State-of-the-Art Imaging Workshop.
AB  - Modern imaging techniques that can provide functional information on tumor
      vascularization, metabolic activity, or cellularity have seen significant
      improvements over the past decade. However, most of these techniques are
      currently not broadly utilized neither in clinical trials nor in clinical
      routine, although there is a large agreement on the fact that conventional
      approaches for therapy response assessment such as Response Evaluation Criteria
      in Solid Tumors or World Health Organization criteria-that exclusively focus on
      the change in tumor size-are of less value for response assessment in modern
      thoracic oncology. The aim of this article comprises two parts: a short review of
      the most promising state-of-the-art imaging techniques that have the potential to
      play a larger role in thoracic oncology within the near future followed by a
      meeting report including recommendations of an interdisciplinary expert panel
      that discussed the potential of the different techniques during the Dresden 2013
      Post World Congress of Lung Cancer (WCLC)--International Association for the
      Study of Lung Cancer (IASLC) meeting. It is intended to provide a comprehensive
      summary about ongoing trends and future perspectives on functional imaging in
      thoracic oncology.

PMID- 25611227
TI  - Endobronchial ultrasound versus mediastinoscopy for mediastinal nodal staging of
      non-small-cell lung cancer.
AB  - INTRODUCTION: Correct mediastinal staging is critical for determination of the
      most appropriate management strategy in patients with non-small-cell lung cancer
      (NSCLC). The purpose of this study was to compare the diagnostic performance of
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with
      that of mediastinoscopy in patients with NSCLC. METHODS: A prospective trial was
      conducted in a tertiary referral center in Korea. Patients with histologically
      proven NSCLC and suspicion for N1, N2, or N3 metastasis were enrolled. Each
      patient underwent EBUS-TBNA followed by mediastinoscopy. Surgical resection and
      complete lymph node dissection were conducted in patients for whom no evidence of
      mediastinal metastasis was apparent after mediastinoscopy. RESULTS: In total, 138
      patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and
      mediastinoscopy. N2/N3 disease was confirmed in 59.1% of the patients. The
      diagnostic sensitivity, specificity, accuracy, positive predictive value, and
      negative predictive value (NPV) of EBUS-TBNA on a per-person analysis were 88.0%,
      100%, 92.9%, 100%, and 85.2%, respectively. The diagnostic sensitivity,
      specificity, accuracy, positive predictive value, and NPV of mediastinoscopy on a
      per-person analysis were 81.3%, 100%, 89.0%, 100%, and 78.8%, respectively.
      Significant differences in the sensitivity, accuracy, and NPV were evident
      between EBUS-TBNA and mediastinoscopy (p < 0.005). CONCLUSIONS: EBUS-TBNA was
      superior to mediastinoscopy in terms of its diagnostic performance for
      mediastinal staging of cN1-3 NSCLC. Because EBUS-TBNA is both less invasive and
      affords superior diagnostic sensitivity, it should be the first-line procedure
      performed in patients with NSCLC.

PMID- 25611228
TI  - Quality of life analyses from the randomized, open-label, phase III PointBreak
      study of pemetrexed-carboplatin-bevacizumab followed by maintenance pemetrexed
      bevacizumab versus paclitaxel-carboplatin-bevacizumab followed by maintenance
      bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung
      cancer.
AB  - INTRODUCTION: Treatment impact on quality of life (QoL) informs treatment
      management decisions in advanced nonsquamous non-small-cell lung cancer (NS
      NSCLC). QoL outcomes from the phase III PointBreak trial are reported. METHODS:
      Chemonaive patients (n = 939) with stage IIIB/IV nonsquamous non-small-cell lung
      cancer and Eastern Cooperative Oncology Group performance status 0 to 1 were
      randomized (1:1) to pemetrexed-carboplatin-bevacizumab (pemetrexed arm) or
      paclitaxel-carboplatin-bevacizumab (paclitaxel arm). Patients without progressive
      disease received maintenance pemetrexed-bevacizumab (pemetrexed arm) or
      bevacizumab (paclitaxel arm). QoL was assessed using Functional Assessment of
      Cancer Therapy (FACT)-General (FACT-G), FACT-Lung (FACT-L), and FACT/Gynecologic
      Oncology Group-Neurotoxicity (FACT-Ntx) instruments. Subscale scores, total
      scores, and trial outcome indices were analyzed using linear mixed-effects
      models. Post hoc analyses examined the association between baseline FACT scores
      and overall survival (OS). RESULTS: Mean score differences in change from
      baseline significantly favored the pemetrexed arm for the neurotoxicity subscale
      score, FACT-Ntx total scores, and FACT-Ntx trial outcome index. They occurred at
      cycle 2 (p < 0.001) and persisted through induction cycles 2 to 4 and six
      maintenance cycles. Investigator-assessed, qualitative, drug-related differences
      in grade 2 (1.6% versus 10.6%) and grade 3 (0.0% versus 4.1%) sensory neuropathy
      and grade 3/4 fatigue (10.9% versus 5.0%, p = 0.0012) were observed between the
      pemetrexed and paclitaxel arms. Baseline FACT-G, FACT-L, and FACT-Ntx scores were
      significant prognostic factors for OS (p < 0.001). CONCLUSIONS: Randomized
      patients reported similar changes in QoL, except for less change from baseline in
      neurotoxicity on the pemetrexed arm; investigators reported greater neurotoxicity
      on the paclitaxel arm and greater fatigue on the pemetrexed arm. Higher baseline
      FACT scores were favorable prognostic factors for OS.

PMID- 25611230
TI  - Erlotinib efficacy in NSCLC patients with high polysomy of chromosome 7 and
      EGFR/KRas wild-type tumors.
AB  - BACKGROUND: More than even before, the efficacy of epidermal growth factors
      (EGFRs) tyrosine kinase inhibitors in non-small-cell lung cancer patients
      carrying EGFR wild-type tumors has been under investigation. EGFR wild-type
      patients represent a large and heterogeneous group of patients. In this setting,
      the role played by high polysomy of chromosome 7 still remains controversial.
      Indeed, previous reports did not discriminate between chromosome 7 high polysomy
      and EGFR amplification and/or did not investigate the concurrent presence of EGFR
      and KRas mutations. METHODS: We retrospectively collected data from 163 patients
      analyzed for EGFR status (mutation, amplification, chromosome 7 trysomy, and
      polysomy), in addition to KRas mutation, between 2000 and 2010 in our institute.
      Erlotinib was administered to 73 of them. Objective responses and progression
      free survivals to erlotinib were evaluated. RESULTS: High polysomy of chromosome
      7 characterized 17% (28 of 163) of EGFR/KRas wild-type tumors, independently of
      smoking status. In this group, 13 patients received erlotinib at progression. The
      treatment led one complete and four partial responses, and five stable diseases.
      Two patients progressed. One patient was lost to follow-up. The mean time to
      progression was 9 months. CONCLUSION: Among the EGFR wild-type population, when
      analyzed separately, high polysomy of chromosome 7 was the only molecular feature
      conferring clear signs of sensitivity to erlotinib. Therefore, the evaluation of
      high polysomy of chromosome 7 could become a helpful tool to predict for the
      benefit from epidermal growth factors tyrosine kinase inhibitors in selected
      cases.

PMID- 25611229
TI  - SWOG S0722: phase II study of mTOR inhibitor everolimus (RAD001) in advanced
      malignant pleural mesothelioma (MPM).
AB  - INTRODUCTION: The PI3K/Akt/mammalian target of rapamycin pathway is activated in
      a majority of malignant pleural mesotheliomas (MPM). We evaluated the activity of
      everolimus, an oral mammalian target of rapamycin inhibitor, in patients with
      unresectable MPM. METHODS: MPM patients who had received at least one but no more
      than two prior chemotherapy regimens, which must have been platinum-based, were
      treated with 10 mg of everolimus daily. The primary endpoint was 4-month
      progression-free survival (PFS) by RECIST 1.1. RESULTS: A total of 59 evaluable
      patients were included in the analysis. The median duration of treatment was 2
      cycles (56 days). Overall response rate was 2% [95% confidence interval (CI): 0
      12%] by RECIST 1.1 and 0% (0-10%) by modified RECIST for MPM. The 4-month PFS
      rate was 29% (95% CI: 17-41%) by RECIST 1.1, and 27% (95% CI: 16-39%) by modified
      RECIST. The median PFS was 2.8 months (95% CI: 1.8-3.4) by RECIST 1.1. The median
      overall survival was 6.3 months (95% CI: 4.0-8.0). There was no difference in PFS
      among patients who received one or two prior chemotherapy regimens (p = 0.74).
      There was no difference in overall survival between patients with epithelioid
      histology versus other types (p = 0.47). The most common toxicities were fatigue
      (59%), hypertriglyceridemia (44%), anemia (42%), oral mucositis (34%), nausea
      (32%), and anorexia (32%). The most common grade 3 to 4 toxicities were fatigue
      (10.2%), anemia (6.8%), and lung infection (6.8%). CONCLUSION: Everolimus has
      limited clinical activity in advanced MPM patients. Additional studies of single
      agent everolimus in advanced MPM are not warranted.

PMID- 25611231
TI  - Tumor relapse after thoracic surgery?

PMID- 25611232
TI  - Multiorgan autoimmune manifestations associated with thymoma.

PMID- 25611233
TI  - The importance of being solid or partially solid for a solitary pulmonary nodule.

PMID- 25611234
TI  - A reply to Bertolaccini et al.

PMID- 25611235
TI  - Difference in outcome between types of KRAS mutation may point toward difference
      in tumor biology.

PMID- 25611236
TI  - KRAS-G12C mutation is associated with poor outcome in surgically resected lung
      adenocarcinoma.

PMID- 25611237
TI  - Validation of a Manual Protocol for BRAF V600E Mutation-specific
      Immunohistochemistry.
AB  - Detection of BRAF V600E has diagnostic, prognostic, and therapeutic relevance.
      The recently developed BRAF V600E mutation-specific antibody has evolved into a
      feasible alternative to DNA analysis. The plethora of immunohistochemical
      protocols makes implementation tedious and, here we tested a set of manual and
      automated protocols and compared test performance with sequencing results. For
      assays, we employed formalin-fixed, in part decalcified, and paraffin-embedded
      tissue samples. Empiric testing of manual protocols included 10 variables in 17
      protocols. Automated immunohistochemical staining and BRAF pyrosequencing served
      as independent test methods. Test performance measures were compared without
      considering 1 method as a standard. Four well-fixed samples (2WT/2Mut) were used
      for testing of all protocols and indicated 2 correctly classifying procedures.
      Practical performance assessment employed 33 independent tissue samples, composed
      of 27 leukemias (by pyrosequencing: 8 wild-type; 18 mutated; 1 noninformative)
      and 6 melanomas (V600E; V600K; wild-type, 2 each). Manual V600E staining was
      positive in 20 cases (19 of 20 V600E-containing samples plus the 1 sample that
      was noninformative), whereas all wild-type and V600K cases were immunonegative.
      Manual or automated staining as well as pyrosequencing would have missed an equal
      number of V600E-mutated cases and the correlation coefficient for these methods
      was 0.75 to 0.93 (substantial to almost perfect); the Youden index was 0.95.
      Detection of V600E-mutated BRAF at the protein level in routine and decalcified
      tissue samples is possible, and the presented manual protocols should expedite
      implementation in routine diagnostic practice. Our results indicate that both
      molecular techniques should be considered complementary.

PMID- 25611238
TI  - The prognostic and predictive significance of PARP-1 in locally advanced breast
      cancer of Egyptian patients receiving neoadjuvant chemotherapy.
AB  - PURPOSE: PARP-1 is a chromatin-associated enzyme that has a role in DNA repair
      and cell death. PARP-1 inhibitors are suggested therapy specifically for BRCA
      deficient breast carcinoma; however, their efficacy in sporadic breast cancer is
      under investigations. This study aimed to evaluate the PARP-1 in locally advanced
      breast cancer (LABC) cases to determine its predictive significance for outcome
      and response to neoadjuvant chemotherapy (NCT). MATERIALS AND METHODS: This
      retrospective study was conducted on 84 LABC cases. Immunohistochemical
      expression of nuclear PARP-1 (nPARP-1) and cytoplasmic PARP-1 (cPARP-1) was
      evaluated in pretreatment needle core biopsies (NCBs). Results were correlated
      with clinicopathologic features, overall survival (OS), disease-free survival
      (DFS), and response to NCT in postoperative specimens. RESULTS: High nPARP
      1expression was observed in 64/84 (76%) of cases and was significantly associated
      with a lower lymph node stage (P=0.04). High cPARP-1 was observed in 40/84 (48%)
      of cases and it was significantly associated with lower lymph node stage
      (P=0.022) and lower tumor grade (P=0.050). High nPARP-1 expression was
      significantly associated with high cPARP-1 expression (P=0.005). Low cPARP-1
      expression was associated with no response to chemotherapy in tumor site
      (P=0.021). According to the univariate survival analysis, high nPARP-1 and high
      cPARP-1 were significantly associated to longer OS (P=0.017 and P=0.019,
      respectively). High nPARP-1 but not cPARP-1 showed trend toward improved OS in
      multivariate Cox-regression analysis (P=0.053). CONCLUSION: PARP-1
      immunohistochemical expression is a marker of good prognosis and is predictive of
      response to NCT in LABC.

PMID- 25611239
TI  - FISH Technique as Additional Diagnostic Tool in Differentiating Testicular
      Pulmonary Metastasis from Pulmonary Congenital Cystic Adenomatoid Malformation.

PMID- 25611240
TI  - The Loss of p16 Expression Worsens the Prognosis of OSCC.
AB  - Oral squamous cell carcinoma is the most common neoplasia of the mouth.
      Downregulation of p16(INK4a) (a cyclin-dependent kinase inhibitor) has been
      reported for mouth cancer and it is believed that its inactivation is an early
      event in oral carcinogenesis. The goal of this article is to quantitatively
      report expression of p16(INK4a) and the state of methylation in oral squamous
      cell carcinoma, and evaluate its relationship with the clinical and prognostic
      factors, in addition to setting out a multivariate model that predicts survival.
      The mean expression of p16(INK4a) was 7.70 (SD=14.07) (F=0.894; P=0.449).
      According to the semiquantitative analysis, there were statistically significant
      differences, where 19 cases were negative (<2 %), 11 at initial stages, and 8 at
      advanced stages (chi(2)=6.016; P<0.05). The methylation of p16(INK4a) was not
      associated with any of the clinical or pathologic variables. Kaplan-Meier curve
      showed a better survival for patients in initial stages (40.72 mo) compared to
      those in advanced stages (28.6 mo) (P<0.01). Survival was also reduced in a
      statistically significant manner in patients with any degree of dysplasia in the
      adjacent margin (P<0.05). During univariate Cox regression analysis, it was
      observed that individuals with relapse had a higher risk (almost 9 times higher)
      [P<0.001; hazard ratio=8.91; 95% confidence interval (CI), 4.18-19.02]. During
      the Cox multivariate analysis for each unit of decrease in p16(INK4a), the risk
      increased by 1.06) (P<0.05; hazard ratio=0.94; 95% CI, 0.89-1.00). p16(INK4a)
      expression is reduced with advancing tumor stage and its gene silencing is
      associated with an increased risk of death.

PMID- 25611241
TI  - Breast Cancer Molecular Subtypes and Oxidative DNA Damage.
AB  - BACKGROUND: Oxidative stress is thought to play a major role in etiology of many
      cancers, including breast cancer. 8-hydroxy-2'deoxyguanosine (8-OHdG) is the most
      abundant marker of oxidative DNA damage. The aim of this study was to assess the
      extent of oxidative DNA damage in different breast cancer molecular surrogate
      subtypes to investigate the prognostic relevance and role of oxidative base
      lesion (8-OHdG) in the etiology of breast cancer. MATERIALS AND METHODS: 8-OHdG
      expression was immunohistochemicaly studied on tissue microarrays constructed
      from 152 patients with invasive breast cancer. Expression was correlated with
      other prognostic factors, as well as different breast cancer molecular surrogate
      subtypes such as luminal A, luminal B [human epidermal growth factor receptor 2
      (HER2) negative], luminal B (HER2 positive), HER2-enriched ad triple-negative
      tumors. RESULTS: Triple-negative breast carcinomas (TNBCs) were more frequently 8
      OHdG negative compared with non-TNBCs (P=0.036). There was no statistically
      significant difference between 8-OHdG expression and other breast cancer
      molecular subtypes.In univariate analysis, there was no significant difference
      between 8-OHdG expression and breast cancer-specific death, although in
      multivariate analysis 8-OHdG overexpression was associated with better breast
      cancer-specific survival (BCSS) (odds ratio=0.04, 95% confidence interval, 0.002
      0.62). In Cox regression analysis, patients with moderate and strong 8-OHdG
      expression had 0.9 times smaller breast cancer death hazard ratio than patients
      with negative 8-OHdG expression. CONCLUSIONS: Oxidative stress may have less
      impact in the pathogenesis of TNBCs compared with other surrogate breast cancer
      molecular subtypes. 8-OHdG may be a promising biomarker in the prediction of
      prognosis for breast cancer patients.

PMID- 25611242
TI  - HER2 Genetic Heterogeneity in Gastric Cancer: Evaluation According to the College
      of American Pathologists Breast Cancer Criteria.
AB  - Gastric and gastroesophageal junction (GEJ) adenocarcinomas have been shown to
      display significant HER2 genetic heterogeneity (GH). This is typically seen as a
      cluster of HER2-positive cells but can also take the form of intermingled cells,
      referred to a "mosaic" pattern. GH is not well defined in gastric/GEJ tumors and
      the "mosaic" pattern has never been studied. We sought to evaluate the frequency
      and distribution of the "mosaic" pattern of GH in gastric/GEJ tumors using the
      College of American Pathologists-endorsed breast criteria of 5% to <50% amplified
      nuclei. We also postulated that the lower limit of this GH definition might be
      seen by chance in normal gastric epithelium. A total of 360 consecutive
      gastric/GEJ tumors were tested for HER2 by immunohistochemistry and in situ
      hybridization. Individual tumor cell HER2:CEP17 ratios were calculated for each
      case and the percentage of tumor cells with a ratio >=2.0 determined. In
      addition, 300 normal gastric epithelial cells were scored for HER2 and CEP17
      signals. Overall, 265 cases (73.4%) showed GH. The percentage of amplified cells
      in GH cases linearly correlated with the overall HER2:CEP17 ratio. In normal
      gastric epithelium, a cell with an "amplified" 2:1 ratio was seen in 9.7%
      (29/300) of cells, thus reaching GH. The chance of "GH" in scoring 20 normal
      epithelial cells was 87%. We conclude that GH is very common in gastric/GEJ
      tumors when College of American Pathologists breast criteria are applied and the
      lower threshold is likely of little clinical significance due to the finding
      "amplified" 2:1 nuclei in normal cells. 

PMID- 25611243
TI  - The Utility of Phosphohistone H3 in Breast Cancer Grading.
AB  - The commonly used Nottingham Grading System in breast cancer takes into
      consideration the presence of tubular formation, nuclear pleomorphism, and the
      mitotic index (MI), among which the latter has been shown to be the most powerful
      prognostic factor. In practice, histologic grading is highly subjective, with
      only moderate interobserver reproducibility. Phosphorylation of histone H3 has
      been demonstrated to be a specific event in the mitotic phase, and is negligible
      during interphase. In this study, we evaluated the efficacy of Phosphohistone H3
      (PHH3) in the breast cancer grading of 97 consecutive biopsy specimens. PHH3
      antibodies clearly revealed discrete, strong nuclear immunoreactivity in
      mitotically active cells even under low magnification. The PHH3 MI showed a
      significant correlation with that derived by hematoxylin and eosin (H&E) staining
      as well as the Ki-67 proliferation index. Further, the pairwise kappa-value of
      the MI was significantly increased, and the pairwise agreement was also markedly
      improved by PHH3 immunostaining, although a significant proportion of breast
      cancer cases were upgraded by use of the PHH3 MI. Our data showed that PHH3
      provided a more sensitive and accurate MI with less interobserver variability
      when compared with conventional H&E staining, thus emphasizing its potentially
      increased value in practice. Reconsideration of breast cancer grading with
      integration of PHH3 should be considered if it continues to demonstrate
      superiorly to traditional H&E staining. 

PMID- 25611244
TI  - alpha-Hemoglobin-stabilizing Protein: An Effective Marker for Erythroid
      Precursors in Bone Marrow Biopsy Specimens.
AB  - Accurate analysis of the erythroid lineage is essential in evaluating bone marrow
      biopsies and can be particularly challenging in settings of dyserythropoiesis.
      alpha-Hemoglobin-stabilizing protein (AHSP) is an erythroid-specific chaperone
      protein and represents a potential specific marker for erythroid elements. This
      study defines the immunohistochemical profile of AHSP, as compared with an
      established erythroid marker CD71, in 101 bone marrow biopsies including normal
      marrows and cases of acute pure erythroid leukemia, acute erythroid/myeloid
      leukemia, other types of acute myeloid leukemia, myelodysplastic syndrome,
      chronic myelogenous leukemia, other types of myeloproliferative neoplasm, chronic
      myelomonocytic leukemia, acute lymphoblastic leukemia, plasma cell neoplasm, and
      metastatic carcinoma. In acute pure erythroid leukemia, blasts in 7 of 11 cases
      showed similar reactivity for CD71 and AHSP, whereas less extensive reactivity
      was observed for AHSP as compared with CD71 in the remaining 4 cases. In normal
      marrows and other various disorders, reactivity for AHSP was similar to CD71 and
      was restricted to the erythroid lineage. Mature erythrocytes were negative for
      AHSP as were myeloblasts, lymphoblasts, nonerythroid hematopoietic marrow
      elements, plasma cells, and carcinoma cells. AHSP is an effective marker for
      detection of normal or abnormal erythroid precursors in bone marrow biopsies and
      is a useful addition to an immunohistochemical panel for assessment of neoplastic
      cells of possible erythroid derivation.

PMID- 25611245
TI  - Uroplakin II (UPII), GATA3, and p40 are Highly Sensitive Markers for the
      Differential Diagnosis of Invasive Urothelial Carcinoma.
AB  - Distinguishing between invasive urothelial carcinoma from other genitourinary
      lesions such as prostatic and renal carcinomas can be difficult, and may require
      highly sensitive immunohistochemical markers. GATA-binding protein 3 (GATA3) has
      been reported in a high percentage of urothelial and breast carcinomas. Mouse
      monoclonal uroplakin II (UPII) and p40 antibodies have recently been developed
      and demonstrated high specificity in urothelial carcinoma. This study evaluated
      the immunohistochemical staining sensitivities of UPII, GATA3, p40, and p63 in
      the detection of invasive urothelial carcinoma. UPII, GATA3, and p40 were further
      tested for specificity in lung, breast, colon, kidney, and prostate cancers. In
      all invasive urothelial carcinoma cases, UPII, GATA3, p40, and p63 exhibited
      sensitivities of 77.7%, 83.5%, 85.4%, and 80.6%, respectively. The combination of
      UPII, GATA3, and p40 antibodies stained 94.2% (97/103) of all invasive urothelial
      carcinoma cases, including 92.2% (71/77) of grade 2-3 urothelial carcinomas. In
      addition, GATA3 and UPII showed negative staining in lung squamous cell
      carcinomas and p40 showed negative staining in breast infiltrating ductal
      carcinomas. The combination of UPII, GATA3, and p40 showed negative staining in
      lung adenocarcinoma, colon adenocarcinoma, and renal carcinomas. In conclusion,
      UPII, GATA3, and p40, when used in combination, are highly sensitive in the
      differential diagnosis of invasive urothelial carcinoma. 

PMID- 25611246
TI  - Can SOX-10 or KBA.62 Replace S100 Protein in Immunohistochemical Evaluation of
      Sentinel Lymph Nodes for Metastatic Melanoma?
AB  - BACKGROUND: Microscopic evaluation of sentinel lymph nodes for metastatic
      melanoma relies, in part, on the use of immunohistochemical analysis to identify
      minute metastatic deposits that may be overlooked on routine microscopy. At
      present S100 protein is widely used in this role, in large part for its superior
      sensitivity; however, interpretation is hampered by the presence of benign S100
      protein-positive cellular elements present in every lymph node, leading to
      reduced specificity and consequent difficulties in interpretation. In recent
      years, multiple melanocytic markers have emerged that promise superior
      sensitivity and specificity, including KBA.62 and SOX-10. SOX-10 shows a nuclear
      pattern of staining. In normal tissue it is expressed in Schwann cells,
      melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands.
      KBA.62 is also specific except for staining of endothelial cells and shows a
      membranous staining pattern. This study was undertaken to determine whether
      KBA.62 or SOX-10 could equal (or surpass) the sensitivity of S100 protein while
      offering superior specificity in the immunohistochemical evaluation of sentinel
      lymph nodes for metastatic melanoma. DESIGN: In this study we performed
      immunohistochemical stains for S100 protein, Sox-10, and KBA.62 on 50 lymph nodes
      with proven metastatic melanoma. RESULTS: SOX-10 detected all cases of metastatic
      melanoma (50 of 50 cases; 100%) compared with S100 protein (48 of 50 cases; 96%)
      and KBA.62 (37 of 50 cases; 74%). There was no "background" staining of normal
      cellular elements with SOX-10 or KBA.62. In contrast, S100 protein was expressed
      in scattered dendritic interdigitating reticulum cells in the paracortex of lymph
      nodes, showing cytoplasmic and nuclear positivity, sometimes posing significant
      difficulty in differentiating benign reticulum cells from single cell metastatic
      melanoma. CONCLUSIONS: Our findings suggest that SOX-10 may be superior to S100
      protein for identifying metastatic melanoma in a lymph node. KBA.62 was less
      sensitive than either marker, although more specific than S100 protein.

PMID- 25611247
TI  - Postoperative Uvular Edema in a Child After General Anesthesia via a Laryngeal
      Mask Airway.
AB  - We describe a case of postoperative uvular edema in a pediatric patient who
      underwent general anesthesia via a laryngeal mask airway at our institution.
      Although numerous cases of uvular trauma have been reported in the literature,
      its association with laryngeal mask airway use remains rare. 

PMID- 25611248
TI  - Editorial Comment: Postoperative Uvular Edema in a Child After General Anesthesia
      via a Laryngeal Mask Airway.

PMID- 25611249
TI  - Transient facial nerve palsy after auriculotemporal nerve block in awake
      craniotomy patients.
AB  - In this case series, we describe transient postoperative facial nerve palsy in
      patients after awake craniotomy using selective scalp nerve blocks. In a 1-year
      period, 7 of the 42 patients receiving scalp nerve blocks at our institutions
      developed this complication. This is significant because there is only 1
      previously reported case of postoperative facial nerve palsy related to scalp
      nerve blocks. The exact cause of transient postoperative facial nerve palsy after
      auriculotemporal nerve block is unknown and likely multifactorial. This technique
      may need to be refined to avoid such complications. 

PMID- 25611250
TI  - Postoperative episodic left bundle branch block.
AB  - Transient left bundle branch block (LBBB) associated with physical exertion has
      been described in patients with and without coronary artery disease. A 64-year
      old woman with no history of coronary artery disease underwent Nissen
      fundoplication under general anesthesia. Preoperatively, an exercise-tolerance
      test revealed LBBB, without ischemic symptoms. Intraoperatively, the
      electrocardiogram revealed normal sinus rhythm. Postoperatively, LBBB appeared in
      the absence of clinical symptoms or physiologic stress. The patient reported
      several similar episodes previously. Cardiac enzymes were negative. Subsequent
      electrocardiograms revealed persistence of LBBB. Anesthesiologists should be
      aware of the possibility of perioperative transient LBBB in the absence of
      cardiac ischemia. 

PMID- 25611251
TI  - Anesthetic management during labor and delivery of a multiparous patient
      terminally ill with metastatic breast cancer.
AB  - Multiple ethical issues arise when caring for a terminally ill patient who is
      also pregnant. We present the management of labor and delivery of a 35-year-old
      multiparous patient with stage 4 metastatic breast cancer. The ethical challenges
      in treating a mother and fetus when a terminal illness complicates pregnancy is
      also included. 

PMID- 25611252
TI  - Controlled synthesis and assembly into anisotropic arrays of magnetic cobalt
      substituted magnetite nanocubes.
AB  - Cubic cobalt-substituted magnetite CoxFe3-xO4 nanocubes (NCs) with uniform
      composition distributions of Co, Fe and O in the NCs, obtained via solution
      synthesis, are reported in this paper. Through the control of the reaction
      conditions, the size of the cubic NCs could be tuned from 35 to 110 nm. It was
      found that the cubic shape could easily induce the (400) orientation of the NCs
      on a Si substrate, and applying an external magnetic field in the out-of-plane
      direction could further enhance the (400) orientation of these NCs on the Si
      substrate. The highest coercivity of 2.07 kOe could be obtained by assembling the
      NCs in the external magnetic field. The reported magnetic cobalt-substituted
      magnetite NCs provide an ideal class of building blocks for studying
      ferrimagnetic nanoparticle (NP) assemblies with easily controlled magnetic
      alignment for magnetic tape recording with ever increased areal storage density. 

PMID- 25611254
TI  - Quinoxaline-Based Cyclo(oligophenylenes).
AB  - A series of fully conjugated quinoxaline-based oligophenylene macrocycles is
      synthesized by Ni(0)-mediated Yamamoto-type diaryl homocoupling of (fluorinated)
      2,3-bis(4'-bromophenyl)quinoxaline precursors. Cyclotrimers and cyclotetramers
      are obtained as the dominant reaction products. The cyclooligomers are fully
      characterized, including single-crystal X-ray structures, and their
      optoelectronic properties are analyzed with respect to possible applications in
      host-guest chemistry and organic electronics. 

PMID- 25611253
TI  - Multi-endpoint, high-throughput study of nanomaterial toxicity in Caenorhabditis
      elegans.
AB  - The booming nanotechnology industry has raised public concerns about the
      environmental health and safety impact of engineered nanomaterials (ENMs). High
      throughput assays are needed to obtain toxicity data for the rapidly increasing
      number of ENMs. Here we present a suite of high-throughput methods to study
      nanotoxicity in intact animals using Caenorhabditis elegans as a model. At the
      population level, our system measures food consumption of thousands of animals to
      evaluate population fitness. At the organism level, our automated system analyzes
      hundreds of individual animals for body length, locomotion speed, and lifespan.
      To demonstrate the utility of our system, we applied this technology to test the
      toxicity of 20 nanomaterials at four concentrations. Only fullerene nanoparticles
      (nC60), fullerol, TiO2, and CeO2 showed little or no toxicity. Various degrees of
      toxicity were detected from different forms of carbon nanotubes, graphene, carbon
      black, Ag, and fumed SiO2 nanoparticles. Aminofullerene and ultraviolet
      irradiated nC60 also showed small but significant toxicity. We further
      investigated the effects of nanomaterial size, shape, surface chemistry, and
      exposure conditions on toxicity. Our data are publicly available at the open
      access nanotoxicity database www.QuantWorm.org/nano.

PMID- 25611255
TI  - An extension of Wolf's method for the treatment of electrostatic interactions:
      application to liquid water and aqueous solutions.
AB  - We report the results of molecular dynamics simulations, which indicate that, by
      carefully splitting the electrostatic interactions in short- and long-range
      contributions and employing the charge-neutralization method of Wolf, accurate
      predictions of various properties of liquid water and aqueous solutions can be
      achieved without the need for the Ewald summation. In order to assess the
      accuracy of the proposed approach, several molecular dynamics simulations under
      different thermodynamic conditions are performed, employing various rigid,
      flexible, pairwise additive, and many-body polarizable water models. The
      predictions of the new approach are compared to the benchmark results obtained
      with the Ewald summation. It is found that while in the new approach there are no
      adjustable parameters, such as a damping parameter, the obtained results are more
      accurate than the results of similar approaches that are based on the Wolf
      method, while at the same time less or no additional computational effort is
      required. It is also concluded that the error of the results is smaller or at
      least comparable to the statistical error of a typical molecular dynamics
      simulation. 

PMID- 25611256
TI  - Dithiophenedione-containing polymers for battery application.
AB  - Redox-active polymers have received recently significant interest as active
      materials in secondary organic batteries. We designed a redox-active monomer,
      namely 2-vinyl-4,8-dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-dione that exhibits
      two one-electron redox reactions and has a low molar mass, resulting in a high
      theoretical capacity of 217 mAh/g. The free radical polymerization of the monomer
      was optimized by variation of solvent and initiator. The electrochemical behavior
      of the obtained polymer was investigated using cyclic voltammetry. The
      utilization of lithium salts in the supporting electrolyte leads to a merging of
      the redox waves accompanied by a shift to higher redox potentials. Prototype
      batteries manufactured with 10 wt % polymer as active material exhibit full
      material activity at the first charge/discharge cycle. During the first 100
      cycles, the capacity drops to 50%. Higher contents of polymer (up to 40 wt %)
      leads to a lower material activity. Furthermore, the battery system reveals a
      fast charge/discharge ability, allowing a maximum speed up to 10C (6 min) with
      only a negligible loss of capacity. 

PMID- 25611258
TI  - Dendritic cells and hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) represents a major health burden in the modern
      world. Because current treatment options for HCC are capable of providing good
      survival rates to only a limited number of patients, new therapeutic
      opportunities should be looked upon. The particularities of dendritic cells (DC)
      populations existing in the liver, and their consecutive selective activation of
      certain immunotolerant T-cell subgroups, account for the high success rate of
      allogeneic hepatic transplantation, currently the most efficient treatment for
      HCC. The particularities of dendritic cells (DCs) populations existing in the
      liver, and their consecutive selective activation of certain immunotolerant T
      cell subgroups, account for the high success rate of allogeneic hepatic
      transplantation for HCC. These molecular mechanisms also open new paths towards
      cancer preventing and cancer curative vaccines, as well as successful
      immunotherapy. Our aim was to summarize the main aspects of the biology of DCs
      populations, especially those present in the liver, and to draw attention to
      their current and future roles in the curative treatment of hepatocarcinoma. 

PMID- 25611257
TI  - The inflammatory infiltrate of melanocytic nevus.
AB  - Melanocytic nevi are frequently accompanied by inflammatory cells of different
      types, in varied amounts and distributed in different patterns. In the current
      report, we review the knowledge on inflammation seen in different types of
      melanocytic nevi. As an additional contribution, we studied the lymphocytic
      inflammatory component of Duperrat nevus, as well as the cytotoxic component of
      Sutton nevus, two contributions that we have not found in the literature. We
      conclude that: (a) Duperrat nevus has a mixed inflammatory reaction that includes
      histiocytes, foreign-body multinucleated giant cells, polymorphonuclears,
      lymphocytes (predominantly CD4+) and plasma cells (commonly abundant); (b) common
      melanocytic nevi with reactive inflammatory infiltrate usually show a CD4+
      predominant population; (c) Meyerson nevus commonly shows an inflammatory
      infiltrate mainly made up of CD4+ T-cells; (d) Sutton nevus with halo phenomenon
      is accompanied by a dense inflammatory infiltrate with lymphocytes in a CD4:CD8
      ratio varying from 1:1 to 1:3 and in which most of the CD8+ T-cells do not
      express cytotoxic markers; (e) Wiesner nevus commonly shows a spare lymphocytic
      infiltrate but the nature of the infiltrate has not yet been investigated. 

PMID- 25611259
TI  - Motor unit changes in normal aging: a brief review.
AB  - Aging is explored by multiple lines of research, in a pursuit of understanding
      this natural process. The motor response is usually the main dependent variable
      in studies regarding physical or cognitive decline in aging. It is therefore
      critical to understand how the motor function changes with age. The present
      review, aims at presenting briefly some of the most recently published works in
      the field, focusing on the three key components of the motor unit. The changes
      that the skeletal muscle undergoes aging sarcopenia, alteration of fiber type
      distribution and also intimate metabolic transformations. The neuromuscular
      junction suffers at cellular and molecular level, with possible implications of
      various cell components, mediators and oxidative stress. Motoneuron loss and
      change in their physiological properties accompany remodeling in the motor units.
      The applicability of knowledge in this field lies in possible interventions
      intended to counteract these age-related losses. 

PMID- 25611260
TI  - Corticosterone protects against memory impairments and reduced hippocampal BDNF
      levels induced by a chronic low dose of ethanol in C57BL/6J mice.
AB  - Acute low doses of ethanol can produce reversible memory deficits, but it is
      unknown whether they persist upon chronic use. We investigated whether the
      chronic intake of a low dose of ethanol induces memory impairments in the ethanol
      preferring C57BL/6J mouse strain. Because stress precipitates alcohol abuse and
      the stress hormone corticosterone contributes to memory processes, ethanol
      consumption and toxic effects, we also determined the impact of co-treatment with
      corticosterone on these effects. BDNF contributes to memory function and toxic
      effects of ethanol, therefore its levels were quantified in the hippocampus and
      frontal cortex. Ethanol (1% in drinking water) and corticosterone (250 MUg/mL)
      were administered using the two-bottle choice test to monitor their appetitive
      properties. Spatial and non-spatial memory performance was assessed using the
      spontaneous alternation, object recognition and object location tests. The
      chronic exposure to a low dose of ethanol caused spatial and non-spatial memory
      deficits after withdrawal associated with a reduction in hippocampal BDNF levels,
      which were prevented by co-treatment with corticosterone (~21 mg/kg/day). The
      protective effect of corticosterone on memory was no longer observed at higher
      doses (~41 mg/kg/day), but persisted for hippocampal BDNF levels. C57BL/6J mice
      did not develop an appetence for 1% ethanol, but the addition of corticosterone
      increased voluntary consumption of and preference for the ethanol+corticosterone
      solutions. Although acute low doses of corticosterone (1 mg/kg) were found to
      rescue established memory impairments, this is the first report of a protective
      effect of chronic doses of corticosterone in the range of 20-32 mg/kg, and
      particularly against memory deficits induced by alcohol.

PMID- 25611261
TI  - Matrix metalloproteinases (MMP-3 and MMP-9) implication in the pathogenesis of
      inflammatory bowel disease (IBD).
AB  - Inflammatory bowel disease is a chronic disease, with unknown etiology,
      characterized by a sustained inflammatory cascade that gives rise to the release
      of mediators, capable of degrading and modifying bowel wall structure. The
      present study investigated changes of circulating metalloproteinases (MMP-3, MMP
      9) and CRP levels in patients with ulcerative colitis and Crohn's disease, in
      order to contribute to the elucidation of pathogenesis. We have studied serum
      samples of 67 patients, of which 46 with ulcerative colitis (mean age 44.8 years)
      and 21 affected by Crohn's diseases (mean age 39.52 years), who were hospitalized
      in the Clinic of Gastroenterology of the Emergency County Hospital of Craiova,
      Romania. For the quantitative determination of MMP-3, MMP-9 and CRP, the ELISA
      technique was used. Both patients, with Crohn's disease and ulcerative colitis,
      showed increased production of studied immunomarkers, which were correlated with
      some clinical stages, indicating their involvement in the disease activity. 

PMID- 25611262
TI  - Fibroepithelial polyps - a rare pathology of the upper urinary tract.
AB  - Ureteral fibroepithelial polyps are a rather uncommon pathological entity.
      However, an increase of their incidence was recorded during the recent period,
      probably due to better access to the investigative methods. The aim of this study
      was to assess the diagnosis and endoscopic treatment particularities of these
      cases. Our experience was based on 11 cases evaluated in the last 12 years. The
      mean patients' age was 43 years (between 26 and 54). Hematuria, flank pain,
      suprapubic discomfort and urinary frequency were the main symptoms. Diagnosis was
      based on ultrasonography, IVP (intravenous pyelography), cystoscopy and
      ureteroscopy and confirmed by histopathology. In four cases, smooth polypoid
      masses covered by apparently normal urothelium and protruding through the
      ureteral orifice were discovered. In six cases, the fibroepithelial polyps
      appeared as a large filling defect in the ureter. In another case, a large,
      organized, blood clot protruding from the left orifice imposed ureteroscopy with
      the identification of a mid-ureteral polyp. Ten cases were treated by
      ureteroscopic laser ablation, while transureteral resection was applied in one
      case. After complete excision of the polypoid base, a double-J stent was
      indwelled for six weeks. Histology described the lesions as fibroepithelial
      polyps: hyperplastic urothelium overlying an intact basement membrane with
      extensive submucosal edema, dilated blood vessels, chronic inflammatory cells and
      fibrous stroma. No recurrences were found during a follow-up period of 56 months
      (between 6 and 72 months). Ureteral fibroepithelial polyps represent a rare
      pathology, ureteroscopy being the gold standard diagnostic method. The appearance
      and location of the lesions are pathognomonic, and complete excision may be
      performed by ureteroscopic approach. Recurrences seem to be rare in these tumors.

PMID- 25611263
TI  - Conventional cytology versus liquid based cytology in cervical pathology:
      correspondences and inconsistencies in diagnosis, advantages and limits.
AB  - Liquid Based Cytology (LBC) has replaced Papanicolaou standard cytology due to
      its practical advantages. Our study aimed to analyze the diagnosis correlations
      and differences between the conventional and liquid based cytology. The study
      group has been composed by 104 patients, diagnosed in the Laboratory of Cytology,
      Galati County Hospital, Romania by using both methods on the same patients group.
      Our study revealed a good correlation between the results. Thus, in 78 from the
      total of 104 (75%) analyzed cases, the diagnoses established by conventional
      smears have been identical to that obtained in LBC. The diagnoses have been
      different in 26 (25%) cases, the inherent errors of conventional Pap diagnosis
      being corrected by LBC. LBC resulted in the diagnosis of some entities missed in
      conventional cytology, namely: ASC-US (atypical squamous cells of undetermined
      significance) (one case), ASC-US associated to AGC-NOS (atypical glandular cells
      not otherwise specified) (one case), and HSIL (high-grade squamous
      intraepithelial lesion) associated to AIS (adenocarcinoma in situ) (one case).
      LBC provided the identification of a higher number of cases of associated
      lesions, as LSIL (low-grade squamous intraepithelial lesion) and AGC-NOS (five
      versus two cases), and HSIL and AGC-NOS (seven versus five cases). The national
      experience is mainly based on conventional cytology usage, after Papanicolaou
      staining method. Extremely rare centers have benefited by the necessary
      infrastructure for LBC, thus there are no constant reports in the mainstream. The
      main impediments in large-scale application of this method, in all national
      screening centers are connected to costs for capital investments and by
      conditions of exploitation. Our experience and results support the simultaneous
      use of the two methods. 

PMID- 25611264
TI  - Prognostic biomarkers in endometrial adenocarcinoma.
AB  - Endometrial carcinoma is the most common malignancy in the female genital system
      and has increased in incidence during the past years. Our study was retrospective
      and included 79 patients with diagnosed endometrial adenocarcinoma. The
      parameters investigated in the study included clinical status, menopause, history
      of estrogen intake, obesity, histological results, transvaginal ultrasonography.
      We evaluated the status of the common clinicopathological features and
      immunohistochemical biomarkers of endometrial carcinoma. The main type of
      carcinoma was endometrial endometrioid carcinoma (68 cases), followed by serous
      carcinoma (seven cases). Immunohistochemical study performed included the
      following antibodies: cytokeratin, vimentin, ER, PR, PTEN, p53, beta-catenin, bcl
      2, WT1 and Ki67. The immunohistochemical profile showed significant differences
      between the two subtypes. The majority of cases showed positivity for steroid
      hormones and the positivity correlated with the endometrioid subtype. We observed
      a correlation between p53 overexpression and specific histological alterations. A
      high percentage of Ki67 positivity tumors correlated with grade 3 tumors, as well
      as with a high percentage of p53 positivity. The study shows the importance of
      the use of biomarkers in the positive diagnosis and the guiding of therapeutic
      approach. 

PMID- 25611265
TI  - Investigation of inflammatory activity in ulcerative colitis.
AB  - Inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease are
      lifelong disorders, characterized by the chronic inflammation of all or part of
      our digestive tract. Cytokines have an essential role in the pathogenesis of
      IBDs, because they control the inflammatory response, and the disequilibrium of
      pro-inflammatory/anti-inflammatory cytokines may lead directly to tissue
      destruction. Histopathologically, these diseases are characterized by the extent
      and the distribution of mucosal architectural abnormality, the cellularity of the
      lamina propria and the present cell types, but these features frequently overlap.
      We performed a prospective study, which included 46 patients diagnosed with
      ulcerative colitis (UC) (gender ratio 25 males/21 females, mean age 44.8 years)
      and 30 subjects, with similar demographic characteristics, which were selected
      from the patients investigated for other digestive disorders, unaffected by UC.
      Serological investigations were performed by quantitative determination of IL-17,
      IL-13, and CRP using ELISA sandwich technique. We have achieved significantly
      higher concentrations of IL-13, IL-17 and CRP in the serum of patients with UC,
      compared to the control group. We have found in our study correlations between
      ulcerative colitis activity and serum levels of interleukins, IL-13 and IL-17.
      Because IL-17 serum levels were significantly correlated with the disease
      severity and only cytokine had a significantly statistic correlation with high
      serum levels of CRP in UC patients, IL-17 can be considered an important progress
      inflammation marker of this disease.

PMID- 25611266
TI  - The regular distribution and expression pattern of immunosuppressive cytokine IL
      35 in mouse uterus during early pregnancy.
AB  - Cytokines within the uterus are critical in the maternal-fetal immune regulation.
      Immunosuppressive cytokine IL-35 was recently discovered inhibitory cytokine,
      which were pivotal in the establishment of immune tolerance against self-antigens
      and antigens encountered in foreign implantation. In order to analyze the role of
      IL-35 in maternal-fetal immune tolerance, the expression patterns of IL-35 in
      mouse endometrium were studied during early pregnancy by immunohistochemistry,
      ELISA and quantitative real-time PCR. As results, we found that IL-35 positive
      cells in the uterus showed significant distribution difference after fetal
      implantation, which mainly distributed in luminal epithelium and glandular
      epithelium of mouse uterus from gestational day 1 to 2, and glandular epithelium
      and stroma from gestational day 4 to 7. The number of positive cells,
      immunoreactive scores, protein and mRNA expression of IL-35 showed firstly
      increased and then decreased with the increase of pregnancy day. The largest
      contents of IL-35 in the uterus were detected on gestational day 4. Compared with
      non-pregnant mice, pregnant mice showed the significantly increased mRNA
      expression of Ebi3 (Epstein-Barr virus-induced gene 3, IL-35 subunit) in the
      endometrium on gestational day 2 and the highest level of expression on
      gestational day 4. The mRNA expression of p35 (IL-35 subunit) was significantly
      lower than that of Ebi3 gene and showed the inconsistent change from gestational
      day 5 to 7. However, the significant correlation existed between the
      immunohistochemical expression, contents and mRNA expression of IL-35. These
      results indicated that IL-35 contributed to the establishment and maintenance of
      maternal-fetal tolerance during early pregnancy. 

PMID- 25611267
TI  - Ultrastructural features of human adipose-derived multipotent mesenchymal stromal
      cells.
AB  - Multipotent mesenchymal stromal cells (MMSCs) are plastic-adherent cells with a
      well-established phenotype. Equine, but not human, adipose MMSCs have been
      characterized ultrastructurally. The purpose of our study was to evaluate
      ultrastructurally the adipose-derived human MMSCs. Cell cultures were prepared
      from human lipoaspirate. The flow cytometry evaluation of surface markers of
      cultured cells confirmed the expected profile of MMSCs, that were positive for
      CD73, CD90 and CD105, and negative for CD34 and CD45. We examined these human
      adipose-derived MMSCs in transmission electron microscopy (TEM) by Epon en-face
      embedding the fixed MMSCs. The main ultrastructural features of MMSCs were the
      extremely rich content of endosomal/vesicular elements, long mitochondria,
      dilated RER (rough endoplasmic reticulum) cisternae, and abundant intermediate
      filaments and microtubules. We found two types of MMSCS prolongations: (a) thick
      processes, with opposite, vesicular and filaments-rich, sides and (b) slender
      processes (pseudopodes and filopodes), with occasional proximal dilated segments
      housing mitochondria, vesicles and secretory granules. These TEM features of
      MMSCs characterized an in vitro cell population and could use to distinguish
      between different cell types in culture.

PMID- 25611268
TI  - S100-positive dendritic cells in squamous cell laryngeal cancer.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells, and induce
      antigen-specific immune responses. DC are believed to evolve into tumor-antigen
      pulsed cells and then to migrate to local lymph nodes, where they activate anti
      tumor immune responses. This theory is supported by studies showing that high DC
      densities are associated with favorable prognosis in some tumor types. In the
      present study, we evaluated 40 primary and metastatic laryngeal carcinomas for
      the presence of DC, using immunohistochemistry with the anti-S100 protein
      antibody. We analyzed the relationship between the degree of infiltration by S100
      positive (S100+) DC and prognostic factors, including histological subtype,
      histological grade, peritumor inflammatory infiltration, and stromal desmoplasia.
      The results show that in all evaluated laryngeal cancers S100-positive cells were
      significantly more frequent in the tumor stroma. Primary tumors with nodal
      metastases showed more significant differences in intraepithelial and stromal DC
      distribution than tumors without nodal metastases. A significant higher S100+ DC
      was also noticed in the desmoplasic stroma of lymph nodes. The subtype with
      keratinization had a significant higher S100-positive cells infiltration than the
      adenoid/transitional subtype. The infiltration rate of intraepithelial S100+ DC
      was much higher in well-differentiated (G1) tumors. No significant correlation
      between S100-positive cells and peritumoral inflammatory infiltration and stromal
      desmoplasia was found. In conclusion, dendritic cells need multiple, much more
      complex investigations. This work should be regarded as a preliminary
      investigation. 

PMID- 25611269
TI  - Detection of early laryngeal cancer and its precursor lesions by a real-time
      autofluorescence imaging system.
AB  - The prognosis of laryngeal carcinoma patients can be improved by early diagnosis.
      The autofluorescence endoscopy has been developed to gain more information about
      the biologic character of the precancerous or cancerous lesions. The aim of the
      present study was to evaluate the diagnostic potential and limitations of this
      imaging technique applied during indirect laryngoscopy and comparing with white
      light and microlaryngoscopy with biopsy. In a prospective study, 56 patients with
      suspected precancerous or cancerous lesions were investigated preoperatively by
      white light and fluorescence endoscopy during indirect laryngoscopy. The
      procedure was followed by microlaryngoscopy and biopsy. Results were compared to
      histopathological findings. Normal laryngeal mucosa displayed a typical green
      fluorescence, moderate to high epithelial dysplasia, in situ carcinoma and cancer
      showed a diminished green fluorescence. In 47 of 56 (84%) cases, we found
      concordant results. The experience from this study shows that autofluorescence by
      indirect laryngoscopy may be a useful complementary method for detecting
      laryngeal malignancies. Its advantages are non-invasiveness, high sensitivity and
      repeatability. 

PMID- 25611270
TI  - E-cadherin and alpha-SMA expression in the epithelial-mesenchymal transition of
      salivary glands pleomorphic adenomas.
AB  - The pleomorphic adenoma, known also as mixed tumor of epithelioma with
      reshuffling stroma, is the most frequent salivary gland tumor, representing 45
      75% of the total salivary gland tumors. In our study, we have investigated the
      immunohistochemical expression of E-cadherin and alpha-smooth muscle actin (alpha
      SMA) in 15 cases of pleomorphic adenoma of salivary glands. We noticed the
      constant presence of E-cadherin reactivity at the level of luminal cells that
      cover the proliferative structures of ductal-cystic type, which gradually
      disappears to the periphery. At the level of epithelial proliferative solid
      areas, the reactivity for E-cadherin was inconstant and heterogeneous, while
      alpha-SMA expression increased. This aspect indicated the involving of epithelial
      mesenchymal transition process in the evolution of pleomorphic adenoma. 

PMID- 25611271
TI  - Modulating factors of progenitor stem cell kinetics in STEMI patients undergoing
      primary angioplasty - a pilot study.
AB  - AIMS: To investigate the circulating progenitor stem cells (cPCs) count evolution
      during seven days hospitalization period in ST segment elevation myocardial
      infarction (STEMI) patients, and to correlate their evolution with some clinical
      and angiographic parameters. MATERIALS AND METHODS: Twelve Caucasian patients
      with STEMI undergoing primary percutaneous coronary intervention (PCI) were
      enrolled. Blood samples were obtained in the emergency room and then daily, for
      seven days, we evaluated the number of cPCs (CD34+CD45+, CD133+CD34+CD45+,
      KDR+CD34+CD45+ and KDR+CD133+CD34+CD45+) by flow cytometry using fluorochrome
      marked specific monoclonal antibodies. RESULTS: There is a statistically
      significant increase in cPCs counts in the following days after STEMI, with a
      different behavior depending on their phenotype. Mature cPCs (CD34+CD45dim,
      KDR+CD34+CD45dim) have two fairly similar peaks, first around the third day of
      evolution followed by a short decrease and a new raise in the seventh day, the
      more immature cPCs (CD133+CD34+CD45dim, KDR+CD133+CD34+CD45dim) have just one
      spike on the third day, and then almost disappear from the peripheral
      circulation. In a multivariate regression analysis, preprocedural TIMI
      (Thrombolysis In Myocardial Infarction) flow, postprocedural myocardial blush and
      LVEF (Left Ventricular Ejection Fraction) proved to be independent predictors for
      cPCs variation in the first week after STEMI. CONCLUSIONS: In our study, we
      demonstrated that all four main phenotypes of circulating progenitor stem cells
      boosted up in the next days after STEMI, with different patterns depending on
      cell type; preprocedural TIMI flow, postprocedural myocardial blush and LVEF
      proved to be independent predictors for cPCs mobilization in the first days after
      STEMI.

PMID- 25611272
TI  - Microscopic aspects of the hybrid layer formed by the SE 1-step Futurabond M
      (Voco) adhesive system applied to normal and sclerotic dentin.
AB  - STUDY OBJECTIVES: In vitro evaluation and comparison of the adhesion of a
      generation-7 adhesive system to normal and sclerotic dentin. MATERIALS AND
      METHODS: For this study, sound teeth as well as teeth with sclerotic dentin,
      which had been extracted for periodontal reasons, were prepared. Class 5 cavities
      were prepared, then restored by means of the SE 1-step Futurabond M (Voco)
      adhesive system, as well as the Estelite Sigma Quick (Tokuyama Dental) composite
      resin. For teeth with sclerotic dentin, the hypermineralized superficial layer
      was removed by means of round bur on low speed, then the adhesive system and
      composite resin were applied. These teeth were prepared for microscopic study
      according to the protocol specific to each microscope. For the study involving
      the confocal microscope, the adhesive was mixed with the Evans Blue dye before
      being applied to the tooth, then the same protocol was followed. RESULTS: When
      applied to normal dentin, Futurabond M (Voco), the generation-7 adhesive system,
      forms a hybrid layer with a depth of 20-25 MUm, while it can be noted that it
      pervades 6-8 MUm into the dentinal tubules. When applied to sclerotic dentin, it
      was noted that the adhesive system does not pervade into the tubules, with an
      approximately 10-15 MUm depth of the hybrid layer. CONCLUSIONS: The adhesion to
      sclerotic dentin shows particular aspects. When it is desired to employ
      generation-7 adhesive systems (SE 1-step) on sclerotic dentin, the therapeutic
      approach needs to include the following supplementary stages: removal of the
      superficial hypermineralized layer, as well as predemineralization with 37%
      phosphoric acid; they are the only stages that might improve the adhesion to this
      substrate.

PMID- 25611273
TI  - Identification and phenotypic characterization of the most frequent bacterial
      etiologies in chronic skin ulcers.
AB  - Chronic wounds represent an important burden on the healthcare system, requiring
      frequent hospitalizations and expensive treatments. It is now recognized that a
      primary factor contributing to a non-healing trajectory and a low therapeutic
      response is the biofilm infection. The purpose of this study was to identify the
      bacterial isolates collected from chronic skin wounds of hospitalized patients
      and to evaluate their antimicrobial susceptibility profiles, virulence factors,
      as well as the ability to develop biofilms in vitro. A number of 44 wound samples
      were collected from 39 patients. The isolated strains belonged to seven different
      microbial species, i.e.: Staphylococcus aureus (32 strains), followed by
      Pseudomonas aeruginosa (4), Escherichia coli (3), Klebsiella pneumoniae (2),
      Proteus mirabilis (1), Citrobacter freundii (1), group G beta-hemolytic
      streptococci (1). In comparison to the other isolates, P. aeruginosa strains
      exhibited the highest capacity to develop complex biofilm structures in vitro,
      followed by S. aureus, with insignificant differences between MRSA and non
      methicillin resistant isolates. The Enterobacteriaceae strains expressed less
      virulent phenotypes, lower adherence to epithelial cells and biofilm forming
      capacity, but also significant resistance phenotypes with a potential of
      unfavorable epidemiological outcome. The isolation of MRSA, ESBL-producing
      microorganisms and multiple antibiotic resistant P. aeruginosa suggests the
      potential risk of nosocomial spread and the potential severe outcome in case of
      bacteremia and sepsis. This study represents an important step in elucidating the
      host-wound microbiome interaction, by describing various resistance and virulence
      threats of microorganisms colonizing and/or infecting the chronic wounds.
      However, in order to establish a statistical relevant correlation, larger studies
      are needed.

PMID- 25611274
TI  - Intra-peritoneal chronic loculation in peritoneal dialysis patients - a new
      medical management approach.
AB  - Peritoneal dialysis (PD) limitation as renal replacement therapy is mostly due to
      peritonitis and complications. Formation and persistence of intra-abdominal
      loculations is often under-diagnosed. Encapsulated peritoneal sclerosis (EPS) is
      a life-threatening complication, but malnutrition, recurrent peritonitis and
      early membrane failure are insidious enemies that need to be emphasized. It is
      important to highlight the persistence of intra-abdominal fluid collection after
      clinical resolution of peritonitis in PD patients and to indicate a new medical
      management approach for an early diagnosis. During five years, we selected PD
      peritonitis cases followed by a six months interval free of infections. Ninety
      seven subjects were followed at six months and one year after the first
      peritonitis. Tomography had been performed to patients presenting a positive
      inflammatory state without a specific infectious cause. Subjects presenting
      documented localized fluid collection (31 cases) were divided into: drug-treated
      group and those undergoing laparoscopy by a new surgery technique (seven
      patients); a comparison regarding the clinical state and biohumoral parameters
      was assessed in both groups. The prevalence of intra-abdominal loculation
      following an apparent resolved peritonitis was high (31.9%). The cases undergoing
      laparoscopy presented a better evolution - improved clinical status (p=0.001),
      higher hemoglobin values (p=0.06), significant lower doses of erythropoietin
      requirement (p=0.03), improved dialysis adequacy (p=0.005) and inflammatory
      state. In cases with confirmed fluid encapsulated loculation, an active attitude
      (screening imaging protocol and laparoscopic exploration) appears to be
      mandatory, decreasing the risk of EPS, a serious complication which pathology and
      treatment are incompletely understood. 

PMID- 25611275
TI  - Morphological and functional characterization of femoral head drilling-derived
      mesenchymal stem cells.
AB  - Adult mesenchymal stem cells (MSCs) were primary identified as bone marrow
      derived cells, fibroblast-like morphology, and adherent to plastic surfaces of in
      vitro culture plate. Their identification criteria evolved in time to a well
      established panel of markers (expression of CD73, CD90, and CD105) and functional
      characteristics (adipogenic, osteogenic, and chondrogenic trilineage
      differentiation ability), which can be applied to adult mesenchymal stem cells
      obtained from other tissue sources. We tried to assess the potential stemness of
      femoral head drilling-derived cells as a new source of mesenchymal stem cells (FH
      MSCs). For this purpose, we used the morphological and ultrastructural
      characteristics defined by scanning and transmission electron microscopy and
      spindle-shape cellular body, fibroblast-like, with few thick elongations
      (lamellipodia) and numerous fine, thin cytoplasmic projections (filopodia) that
      extend beyond the edge of lamellipodia. Immunophenotypical analysis was performed
      by flow cytometry and immunocytochemical methods and we showed that FH-MSCs share
      the characteristic markers of MSCs, expressing CD73, CD90, CD105, and being
      positive for vimentin, and c-kit (CD117). Proliferation rate of these cells was
      moderate, as revealed by Ki67 immunostaining. Regarding the functional
      characteristics of FH-MSCs, after appropriate time of induction in specific
      culture media, the cells were able to prove their trilineage potential and
      differentiated towards adipocytic, osteogenic, and chondrogenic lineage, as
      revealed by immunofluorescent staining. We may conclude that femoral head
      drilling-derived cells can be used as a novel source of stem cells, and employed
      in diverse clinical settings. 

PMID- 25611276
TI  - Analysis of neuromuscular parameters in patients with multiple sclerosis and gait
      disorders.
AB  - Gait is a motor activity that requires understanding the dynamics and functional
      anatomical elements that make possible its cyclical conduct. Patients with
      multiple sclerosis record impaired balance and gait due to the process of
      demyelination, disorders that can be estimated by quantifying neuromuscular and
      cortical parameters. The aim of this paper is to present both an analysis of
      these parameters in the thigh muscles and an evaluation of cortical parameters
      obtained by visual evoked potentials (VEP). PATIENTS AND METHODS: The study was
      conducted on a group of 13 patients (mean age 38 years) with multiple sclerosis
      (MS), who had clinically detectable gait disturbance. Evaluation methods used
      were tensiomyography (TMG) and VEP, the monitored parameters were: contraction
      time (Tc), stance time (Ts), displacement (Dm), if TMG in the two muscle groups
      of the thigh (biceps femoris and right femoris), and if VEP the assessed waves
      were N75, P100, N135-145. RESULTS: There were estimated the average values of
      latency and duration of the three analyzed waves in VEP, the values of wave N135
      145 were far higher than physiological values. In terms of TMG values, they
      results indicate the existence of a clear right-left functional asymmetry.
      DISCUSSION AND CONCLUSIONS: Analyzing these results, we note an increase in the
      muscular tone of the groups studied, a functional asymmetry agonist/antagonist,
      low speed response to stimulus. Regarding VEP wave parameters, we find
      significant variations of these waves' latencies, particularly of P100 wave,
      while the duration of these waves did not register significant figures. In
      conclusion, we can emphasize a change in muscle structure with predominantly type
      I muscular fibers and inter-neuronal connections between areas of the association
      to substitute the lesions occurred in specific areas.

PMID- 25611277
TI  - Peritumoral inflammatory reaction in colon cancer. Histological and
      immunohistochemical study.
AB  - Colorectal cancer is one of the most frequent malignancies with an increasing
      incidence and prevalence. As in other malignancies, nor etiology, neither
      pathogenesis of colorectal cancer are well known. The link between inflammation
      and colorectal cancer has become a major concern in the past 20 years, since
      several clinical trials have shown that patients with chronic inflammatory
      intestinal diseases have a much higher risk of colorectal neoplasm development.
      In our study, we analyzed peritumoral inflammatory reaction from histological and
      immunohistochemical point of view, in 23 cases of stage III colon adenocarcinoma,
      operated during 2014. The immunohistochemical techniques were used in order to
      emphasize B-lymphocytes, T-lymphocytes, macrophages, mast cells and blood
      vessels. In all cases, we have noted the involvement of inflammatory cells
      present in peritumoral and tumoral stroma, in variable degrees, regardless the
      differentiation of the neoplasm or other known histological feature. In
      particular, the macrophages were the most numerous, especially in areas of
      tumoral necrosis, but also present in the lumen of tumoral glands, or even within
      tumoral cell islands. Mast cells appeared more abundant in the tumor stroma
      around blood vessels and were absent in the areas of tumor necrosis, while B
      cells were almost absent. Tumor stroma showed a well-developed vascular network,
      consisting mainly of small vessels that do not seem to correlate with the
      intensity of the inflammatory reaction. 

PMID- 25611278
TI  - In vivo reflectance confocal microscopy of basal cell carcinoma with cystic
      degeneration.
AB  - Basal cell carcinoma (BCC) is the most common skin cancer, may display various
      clinical aspects, frequently has subclinical extension, and through local
      invasion may induce important tissue damage. Reflectance confocal microscopy
      (RCM) is a modern technique that allows a non-invasive investigation of skin
      structure with a nearly histological resolution, and may achieve an optimal in
      vivo evaluation of skin tumors in combination with dermoscopy. We report a case
      of nodular BCC with areas of cystic degeneration in which in vivo RCM and
      dermoscopy evaluation enabled an accurate diagnosis and a detailed preoperative
      evaluation of tumor margins allowing the optimization of surgical treatment, with
      best aesthetic and functional results. 

PMID- 25611279
TI  - Giant ovarian mucinous cystadenoma with borderline areas: a case report.
AB  - Nowadays, giant ovarian mucinous cystadenomas are a rare condition, due to early
      diagnose and treatment. We report the case of a 44-year-old patient, who was
      diagnosed and admitted in our department with a giant pelvi-abdominal mass. The
      patient was operated with very high-risk consent, thus an enormous ovarian cyst
      of approximately 30 kg was extirpated. Afterwards, an extensive histopathological
      analysis was performed in order to determine the exact clinicopathological entity
      of the giant tumor-enteric type of multilocular mucinous ovarian cyst adenoma
      with borderline areas, with benign proliferation. Although giant ovarian mucinous
      cyst adenoma with borderline areas is an extremely rare condition, when
      encountered it is a real challenge for both surgeon and pathologist. 

PMID- 25611281
TI  - Specific features of a rare form of disseminated necrobiosis lipoidica granuloma
      annulare type: a case report.
AB  - Necrobiosis lipoidica (NL) is a rare dermatosis that has been shown to precede
      the onset of diabetes mellitus in 15% of patients. It is more common in women;
      the average age of the onset is 30 years. Skin lesions of classic NL begin as a
      small papule, typically on the bilateral pretibial area. Progressively, these
      papules become indurated plaques with an atrophic, yellow center and multiple
      telangiectatic vessels, and brown-violaceous borders. We present the case of a 57
      year-old male with type II diabetes mellitus from 2004, class II obesity,
      hepatosteatosis and metabolic disturbances who presents a disseminated eruption
      from 2010, formed by indurated plaques with flattened centers and a tendency of
      atrophy and raised, sharply demarcated, red-violaceous borders, having a variable
      diameter between 1.5 and 5 cm. The laboratory findings revealed elevated glucose
      levels between 250 and 300 mg%, high levels of transaminases and lipids.
      Diagnosis of disseminated necrobiosis lipoidica granuloma annulare-type was
      histopathologically confirmed. For the treatment, we have used topical
      corticosteroids and Tacrolimus 0.1% and systemic vasodilators. We consider this
      rare case interesting because has some peculiarities, as: disseminated lesions
      extend over the characteristic areas for necrobiosis lipoidica, the
      characteristic features of lesions similar to granuloma annulare, gender (male)
      and the onset of the disease over fifth decade. 

PMID- 25611280
TI  - Anomalous pattern of origin of the left gastric, splenic, and common hepatic
      arteries arising independently from the abdominal aorta.
AB  - The celiac trunk is the first unpaired midline branch of the abdominal aorta that
      usually gives rise to the left gastric artery (LGA), the common hepatic artery
      (CHA) and the splenic artery (SpA). Despite this classic arrangement, many
      variations exist. We describe an atypical case of an absent CT and anomalous
      origin of the LGA, CHA and the SpA from the abdominal aorta using multidetector
      computed tomography angiography (MDCTA) in a 72-year-old male patient. The LGA
      arose from the anterior wall of the AA at the level of the T12-L1 intervertebral
      disk [33.8 mm above the origin of the superior mesenteric artery (SMA)]. The SpA
      originated directly from the anterolateral wall of the AA at the junction of the
      upper-third and middle-third of the L1 vertebral body (24.8 mm above the origin
      of the SMA). The CHA branched directly from the anterior wall of the AA at the
      level of the middle-third of the L1 vertebral body (17 mm above the origin of the
      SMA). The 64-slice MDCTA system has become the primary tool for evaluation of
      abdominal blood vessels. It is important to be aware of such a variation as it
      can have a significant impact on surgical and clinical practice. 

PMID- 25611282
TI  - Late onset of HIVAN in a young female - a case report.
AB  - INTRODUCTION: Human Immunodeficiency Virus associated Nephropathy (HIVAN) is a
      relatively frequent pathology among HIV patients, especially in black patients.
      Among about 800 HIV-infected patients from the Western Romania cohort, mainly of
      subtype F, none were diagnosed documented with renal biopsy with HIV-associated
      nephropathy. Renal alterations etiology seems to be complex. Several renal
      abnormalities have been described among HIV-infected patients. Patient, Methods
      and Results: We discuss the case of a 24-year-old white Caucasian female HIV
      infected in 1990 by horizontal transmission, in her first year of life. She was
      diagnosed as late-presenter stage C3 at the age of 10, when she was admitted in
      coma secondary to toxoplasmic encephalitis. The clinical evolution was favorable
      under antiretroviral treatment until 2003 when dyslipidemia and arterial
      hypertension appeared. The first clinical manifestations of nephropathy were
      detected in 2006, with altered values of creatinine clearance. A 7-year follow-up
      of renal impairment shows a descending trend of creatinine clearance values. We
      analyzed the repeated ultrasound findings and renal biopsy was performed in 2013
      revealing aspects of HIVAN. It has become obvious that HIVAN is caused by direct
      effects of HIV-1 virus over kidney structure and also that within the renal
      cells, viral replication is still permitted. In our case, the viral load peaked
      in 2011 at the same time the renal function significantly deteriorated. Her
      lifestyle changes must be taken under consideration - in the last year she has
      been under a low protein regimen. Compliance to antiretroviral treatment improves
      survival rate with a delayed deterioration of renal function to end-stage renal
      disease. CONCLUSIONS: Renal biopsy remains the most important feature in order to
      diagnose HIVAN. Suspicion of HIVAN diagnosis should be taken under consideration
      in the presence of constant proteinuria as well as decreased creatinine clearance
      levels.

PMID- 25611283
TI  - Pagetoid reticulosis Woringer-Kolopp type, a particular variant of mycosis
      fungoides: a case report.
AB  - According to the definition of WHO, pagetoid reticulosis (PR) is characterized by
      the presence of unique skin lesion in the shape of patches or plaques caused by
      the proliferation of atypical T-cells in epidermis. We report the case of a 50
      year-old female, presenting a 50*65 mm erythematous scaly patch, well-defined,
      slightly infiltrated, discrete polycyclic, on the right buttock, which appeared
      and developed in about 6-8 months. The clinical and dermatoscopic aspects
      suggested a Bowen's disease. A skin biopsy was performed. The histological
      examination of the pieces confirmed the presence of monoclonal lymphoid
      infiltrate with obvious phenomena of epidermotropism. Immuno-phenotypically the
      tumoral cells express intensively CD3 and CD8 and focally CD4. Surgical excision
      was performed without radiotherapy and chemotherapy. The patient was followed-up
      for 42 months without local relapses, distant lymph nodes or visceral metastases.
      Microscopic aspect of the lesion corresponds to stage I-II of mycosis fungoides
      (MF) (patches or plaques); the diagnosis was PR Woringer-Kolopp type. The most
      recent classification of skin lymphomas (WHO, 2008) confirms that the
      immunohistochemical profile of T-cells can be CD4+ and CD8- or CD4- and CD8+, and
      frequently CD30+, in contrast to the classical versions of MF. Pagetoid
      reticulosis type Woringer-Kolopp, a rare particular variant of mycosis fungoides,
      is suspected in cases with unique, distinctive lesion and confirmed only by
      histological immunohistochemistry. Treatment consists of surgical excision of the
      lesion with long follow-up. 

PMID- 25611284
TI  - Vertical transmission of HIV/TB in newborns: a case report.
AB  - We are presenting the case of a 19-day-old newborn with HIV-seropositive mother,
      under antiretroviral treatment since birth, who is admitted in the ICU (Intensive
      Care Unit) of the 1st Pediatric Clinic at the Emergency County University
      Hospital in Craiova, Romania, in critical general condition, with severe
      respiratory insufficiency. The examination of the tracheal and bronchial
      secretion revealed positive BK (bacillus of Koch). We considered it was an HIV/TB
      co-infection, the tuberculostatic treatment was instituted, but the evolution was
      towards exitus in the 11th day after admission.

PMID- 25611285
TI  - Rare multiple internal root resorption associated with perforation - a case
      report.
AB  - Multiple internal root resorption is a rare outcome of chronic irreversible
      pulpitis. In some cases, a chronic apical periodontitis can be later on
      associated. Usually, the conventional intraoral radiograph is mandatory in
      diagnosis but only CBCT proved to detect the true location, shape and size of
      resorptive defect and, if present, a perforation generated by resorption
      extension through the canal wall. Unlike the intraoral radiograph, CBCT is also
      able to improve the management and the recall evaluation, demonstrating a higher
      accuracy and reliability. 

PMID- 25611286
TI  - Disseminated tuberculosis presenting as febrile seizures with fatal evolution in
      an infant.
AB  - Disseminated tuberculosis with the involvement of brain, liver and gut is a rare
      disease in immunocompetent infant. Early diagnostic and instauration of anti
      tuberculosis therapy is capital because the outcome is poor. Here, we report the
      case of an 11-month-old boy with disseminated tuberculosis of brain, liver
      abdominal lymph nodes, small bowel and lung, which presented with fever,
      generalized tonic-clonic seizure, hemodynamic instability and a history of
      recurrent respiratory tract infections. His father was diagnosed with active
      pulmonary tuberculosis six month ago and family members completed an anti
      tuberculosis chemoprophylaxis regimen.

PMID- 25611287
TI  - Giant dermatofibrosarcoma protuberans - rare form of mesenchymal tissue neoplasm:
      case presentation.
AB  - Dermatofibrosarcoma protuberans (DFSP), a rare type of mesenchymal neoplasm, is
      defined by the WHO as a superficial sarcoma with low-grade malignancy that
      develops in the cutaneous and subcutaneous tissues. The purpose of this paper is
      to present a case of a giant DFSP, with post-traumatic onset in childhood and a
      very long evolution. CLINICAL DATA: 51-year-old Caucasian patient presents for 41
      years a presternal neoplastic lesion, with onset at 10-year-old, few months after
      a strong trauma. The patient addressed for a clinic examination, secondary to a
      spontaneous hemorrhage of the lesion. The local examination reveals the presence
      of a red-purple polynodular neoplastic lesion of 180*110*30 mm, of firm
      consistency, adherent to the subcutaneous tissue, painless, with lateral
      extension at 8 o'clock as an erythematous infiltrated atrophic plaque appearance.
      One of these nodular masses presents surface ulceration and areas of necrosis.
      The CT scan did not detect any infiltration into the pectoral muscle or loco
      regional metastasis. Under general anesthesia a wide surgical excision with free
      macroscopic margins of 3 cm was performed. Histopathological diagnosis was DFSP,
      with evidence of tumoral spindle cells disposed in storiform pattern, embedding
      small adipocyte panicles, creating a lace-like or honeycomb appearance.
      Immunohistochemically, the tumor cells express an intense and diffuse CD34 and
      they are negative for S-100 and SMA. The Ki-67 is focal positive in almost 2-4%.
      Clinical and paraclinical monitoring at 18 months follow-up does not detect any
      local recurrences or metastases, and an excellent quality of life.

PMID- 25611288
TI  - Gruber-Frantz tumor: a very rare pathological condition in children.
AB  - Solid pseudopapillary tumor of the pancreas or Gruber-Frantz tumor is a rare
      pathological entity. Its incidence is even lower in children. This neoplasm has
      low malignant potential and with adequate surgical treatment has a very good
      prognosis. We present the case of a 15-year-old girl admitted in our department
      for an intra-abdominal tumor, diagnosed incidentally on ultrasonography after a
      minor trauma. The CT scan revealed an important mass, apparently localized in the
      liver. Intraoperative assessment found the tumor originating from the pancreatic
      head (12 cm in diameter), well defined, with reddish-brown color, well
      vascularized and heterogeneous consistency. It was completely removed without
      sacrificing other tissues. The postoperative evolution was uneventful. The
      microscopic feature of the tumor, using Hematoxylin and Eosin staining was
      characteristic. Immunohistochemistry confirmed the diagnosis. Four years
      postoperative follow-up showed no recurrence. Only several hundred solid
      pseudopapillary tumors of the pancreas are described in the literature. In
      children, the incidence of this tumor is extremely rare. Some investigators
      believe it is originated from pluripotent primordial stem cells. The clinical
      picture is non-specific. Despite its rarity, this type of tumor should be taken
      into account in the differential diagnosis of abdominal masses in children,
      especially in girls. The diagnosis is made only histologically. Complete surgical
      excision is curative. 

PMID- 25611289
TI  - Oral manifestations of Noonan syndrome: review of the literature and a report of
      four cases.
AB  - Noonan syndrome (NS) was described by Noonan and Ehmke as a multi-system
      disorder, which is typically evident at birth. The incidence of this syndrome is
      estimated to be one per 2500 to one per 1000 and affects both genders. While the
      clinical manifestations of NS have been well documented, the oral manifestations
      have not been extensively discussed. The purpose of the present article is to (a)
      review the oral manifestations of NS reported in the literature, and (b) describe
      four cases (three females and one male) of NS, who presented with short stature,
      cardiac problems and various oral findings. Based on these cases, we conclude
      that many oral anomalies may have possible relationships with NS, which require
      multidisciplinary treatment planning and timely management. The importance of
      oral findings in NS has largely gone unnoticed and it is essential to consider
      oral manifestations as scoring criteria in the diagnosis of NS. 

PMID- 25611290
TI  - Application of a finite element model in the diagnosis process of middle ear
      pathologies.
AB  - The ear is a complex organ that can be affected by various pathologies that are
      still fairly misunderstood. This work tests the possibilities of studying the ear
      and its pathologies using a virtual environment and thus bypassing expensive and
      time-consuming clinical trial. A previous validated finite element model of the
      middle ear was employed to study two pathological states of the middle ear. It
      was shown that the model obtained results very close to the clinical evaluation
      thus proving of being a proper tool for further investigations of middle ear
      pathologies. 

PMID- 25611291
TI  - Oral mucosa self-graft in a patient with invasive conjunctival melanoma: a case
      report.
AB  - Conjunctival melanoma is a rare tumor, while malignant melanoma of the uveal
      tract is the most common primary intraocular tumor in adults. The authors
      highlighted the case of a 68-year-old male patient presented in June 2011 in the
      Ophthalmology Clinic of the Emergency County Hospital of Craiova, Romania,
      accusing foreign body sensation and the appearance of a tumor in the lower fornix
      of his right eye. The patient was clinically and paraclinically investigated, and
      clinically diagnosed with de novo malignant melanoma. The tumor was surgically
      excised and the lower fornix reconstructed with oral mucosa self-graft.
      Histopathological diagnosis was de novo, invasive, ulcerated malignant melanoma
      of the conjunctiva. Ki-67 immunohistochemical staining was also performed. After
      surgery, the patient was sent to the Oncology Department for specific treatment.
      Despite the histological poor prognosis factors present in our patient, two years
      after surgery and chemotherapy, the patient had no clinical sign of local or
      distance recurrent disease. Continuous ophthalmologic and oncological
      surveillance is necessary. 

PMID- 25611292
TI  - Severely altered post-traumatic internal morphology of upper incisors associated
      with biologic width violation - the combined conservative approach.
AB  - This is the report of a case of four upper incisors with multiple
      internal/external resorptions after a falling accident in the childhood and
      subsequent violation of the biologic width by incorrect individual coronal
      restorations. Endodontic orthograde retreatment was performed and mineral
      trioxide aggregate (MTA) was placed as apical plug and to repair the large
      internal resorption. In order to re-establish the biologic width, a controlled
      surgical crown-lengthening procedure was performed. The expression of matrix
      metalloproteinase (MMP)-9 in the gingival tissue was used as a biomarker for the
      presence of inflammation in the hypertrophied gingiva. The one-year control
      revealed the cessation of the resorptive activities and the stability of the
      periodontium. The choice for a conservative combined treatment was essential in
      maintaining the affected teeth in an esthetically challenging area.

PMID- 25611293
TI  - The importance of histopathology findings in lymphomatoid papulosis.
AB  - Lymphomatoid papulosis, part of the controversial group of cutaneous
      lymphoproliferative pseudolymphoma disorders, raises important clinical and
      histopathological problems. It is a chronic, recurrent, clinically characterized
      by popular necrotic lesions and papulo-pustular nodules, sometimes self-limiting
      and characterized by histopathological changes suggestive of cutaneous lymphoma
      (CD30-positive). Since its introduction, in 1968, the term "lymphomatoid
      papulosis" was subject to dispute in terms of classification in malignancies,
      premalignant or benign skin disease. We submit for consideration the case of a
      man with papulo-necrotic skin lesions evolving for about one year with post
      therapeutic remission and relapses, with histopathology of lymphomatoid
      papulosis. The evolution under systemic glucocorticoids has been favorable, with
      remission of skin lesions in about three months without relapses to date. 

PMID- 25611294
TI  - Manganese borohydride; synthesis and characterization.
AB  - Solvent-based synthesis and characterization of alpha-Mn(BH4)2 and a new
      nanoporous polymorph of manganese borohydride, gamma-Mn(BH4)2, via a new solvate
      precursor, Mn(BH4)2.1/2S(CH3)2, is presented. Manganese chloride is reacted with
      lithium borohydride in a toluene/dimethylsulfide mixture at room temperature,
      which yields halide and solvent-free manganese borohydride after extraction with
      dimethylsulfide (DMS) and subsequent removal of residual solvent. This work
      constitutes the first example of establishing a successful, reproducible solvent
      based synthesis route for a pure, crystalline, stable transition metal
      borohydride. The new polymorph, gamma-Mn(BH4)2, is shown to be the manganese
      counterpart of the zeolite-like compound, gamma-Mg(BH4)2 (cubic, a = 16.209(1) A,
      space group Id3a). It is verified that large pores (diameter > 6.0 A) exist in
      this structure. The solvate, Mn(BH4)2.1/2S(CH3)2, is subsequently shown to be the
      analogue of Mg(BH4)2.1/2S(CH3)2. As the structural analogies between Mg(BH4)2 and
      Mn(BH4)2 became evident a new polymorph of Mg(BH4)2 was identified and termed
      zeta-Mg(BH4)2. zeta-Mg(BH4)2 is the structural counterpart of alpha-Mn(BH4)2. All
      synthesis products are characterized employing synchrotron radiation-powder X-ray
      diffraction, infrared spectroscopy and thermogravimetric analysis in combination
      with mass spectroscopy. Thermal analysis reveals the decomposition of Mn(BH4)2 to
      occur at 160  degrees C, accompanied by a mass loss of 14.8 wt%. A small quantity
      of the desorbed gaseous species is identified as diborane (rho(m)(Mn(BH4)2) = 9.5
      wt% H2), while the remaining majority is found to be hydrogen.

PMID- 25611296
TI  - Vacuole dynamics in the salivary glands of Drosophila melanogaster during
      prepupal development.
AB  - A central function of the Drosophila salivary glands (SGs), historically known
      for their polytene chromosomes, is to produce and then release during pupariation
      the secretory glue used to affix a newly formed puparium to a substrate. This
      essential event in the life history of Drosophila is regulated by the steroid
      hormone ecdysone in the late-larval period. Ecdysone triggers a cascade of
      sequential gene activation that leads to glue secretion and initiates the
      developmentally-regulated programmed cell death (PCD) of the larval salivary
      glands, which culminates 16 h after puparium formation (APF). We demonstrate here
      that, even after the larval salivary glands have completed what is perceived to
      be one of their major biological functions--glue secretion during pupariation-
      they remain dynamic and physiologically active up until the execution phase of
      PCD. We have used specific metabolic inhibitors and genetic tools, including
      mutations or transgenes for shi, Rab5, Rab11, vha55, vha68-2, vha36-1, syx1A,
      syx4, and Vps35 to characterize the dramatic series of cellular changes occurring
      in the SG cells between pupariation and 7-8 h APF. Early in the prepupal period,
      they are remarkably active in endocytosis, forming acidic vacuoles. Midway
      through the prepupal period, there is abundant late endosomal trafficking and
      vacuole growth, which is followed later by vacuole neutralization and
      disappearance via membrane consolidation. This work provides new insights into
      the function of Drosophila SGs during the early- to mid-prepupal period.

PMID- 25611297
TI  - Photocatalytic degradation of methylene blue with a nanocomposite system:
      synthesis, photocatalysis and degradation pathways.
AB  - Three different composites, including a calcined FeOOH supported ZnAl layered
      double hydroxide (FeOOH-LDO), a calcined ZnAl layered double hydroxide (ZnAl-LDO)
      and a calcined ZnFeAl layered double hydroxide (ZnFeAl-LDO), were synthesized via
      a sol-gel method, and their activity for the visible light photocatalytic
      degradation of methylene blue (MB) was studied. The composites were characterized
      by PXRD, SEM, and BET techniques, confirming the formation of highly crystalline
      structures. The activity performance of MB degradation was in the following
      order: FeOOH-LDO (~95%) > ZnFeAl-LDO (~60%) > ZnAl-LDO (~23%). In addition, a
      possible photocatalytic degradation reaction mechanism for MB was also proposed.
      Moreover, the frontier electron densities on the atoms of MB were calculated,
      which were in satisfactory agreement with the postulated mechanism. 

PMID- 25611295
TI  - Identification of a novel E-box binding pyrrole-imidazole polyamide inhibiting
      MYC-driven cell proliferation.
AB  - The MYC transcription factor plays a crucial role in the regulation of cell cycle
      progression, apoptosis, angiogenesis, and cellular transformation. Due to its
      oncogenic activities and overexpression in a majority of human cancers, it is an
      interesting target for novel drug therapies. MYC binding to the E-box (5'-CACGTGT
      3') sequence at gene promoters contributes to more than 4000 MYC-dependent
      transcripts. Owing to its importance in MYC regulation, we designed a novel
      sequence-specific DNA-binding pyrrole-imidazole (PI) polyamide, Myc-5, that
      recognizes the E-box consensus sequence. Bioinformatics analysis revealed that
      the Myc-5 binding sequence appeared in 5'- MYC binding E-box sequences at the
      eIF4G1, CCND1, and CDK4 gene promoters. Furthermore, ChIP coupled with detection
      by quantitative PCR indicated that Myc-5 has the ability to inhibit MYC binding
      at the target gene promoters and thus cause downregulation at the mRNA level and
      protein expression of its target genes in human Burkitt's lymphoma model cell
      line, P493.6, carrying an inducible MYC repression system and the K562 (human
      chronic myelogenous leukemia) cell line. Single i.v. injection of Myc-5 at 7.5
      mg/kg dose caused significant tumor growth inhibition in a MYC-dependent tumor
      xenograft model without evidence of toxicity. We report here a compelling
      rationale for the identification of a PI polyamide that inhibits a part of E-box
      mediated MYC downstream gene expression and is a model for showing that phenotype
      associated MYC downstream gene targets consequently inhibit MYC-dependent tumor
      growth. 

PMID- 25611298
TI  - Stability and dynamics of magnetocapillary interactions.
AB  - Recent experiments have shown that floating ferromagnetic beads, under the
      influence of an oscillating background magnetic field, can move along a liquid
      air interface in a sustained periodic locomotion [Lumay et al., Soft Matter,
      2013, 9, 2420]. Dynamic activity arises from a periodically induced dipole-dipole
      repulsion between the beads acting in concert with capillary attraction. We
      investigate analytically and numerically the stability and dynamics of this
      magnetocapillary swimming, and explore other related topics including the steady
      and periodic equilibrium configurations of two and three beads, and bead
      collisions. The swimming speed and system stability depend on a dimensionless
      measure of the relative repulsive and attractive forces which we term the
      magnetocapillary number. An oscillatory magnetic field may stabilize an otherwise
      unstable collinear configuration, and striking behaviors are observed in fast
      transitions to and from locomotory states, offering insight into the behavior and
      self-assembly of interface-bound micro-particles. 

PMID- 25611299
TI  - Evolution of management of gout: a comparison of recent guidelines.
AB  - PURPOSE OF REVIEW: There have been several guidelines on the management of gout
      over the last decade; however, inconsistencies between them create confusion for
      practitioners. This review highlights areas of agreement between guidelines and
      discusses data where disagreements exist. RECENT FINDINGS: For acute gout, the
      guidelines agree that anti-inflammatory treatment should start as soon as
      possible, preferably within 24 hours. Older guidelines preferred NSAIDs or
      colchicine over steroids, but newer ones leave the choice of agent to the
      physician. For colchicine, all guidelines recommend using low dose. Intra
      articular, oral or intramuscular steroids are all described as effective. For
      management of hyperuricemia, indications for initiating urate-lowering therapy
      (ULT) have become more inclusive over the years by requiring lower burden of
      disease severity or including patient comorbidities. Probenecid has fallen out of
      favour with most guidelines favouring allopurinol over febuxostat. Although there
      is a disagreement about timing of initiation for ULT, guidelines recommend
      treating to target of serum urate (sUA) less than 6 mg/dl, and less than 5 mg/dl
      for patients with more severe disease. Concurrent anti-inflammatory prophylaxis
      has gained strong support over the years. SUMMARY: Most guidelines are in
      agreement with recommendations for management of gout and most changes have been
      directional and evolutionary.

PMID- 25611300
TI  - Nutrient stress alters the glycosylation status of LGR5 resulting in reduced
      protein stability and membrane localisation in colorectal tumour cells:
      implications for targeting cancer stem cells.
AB  - BACKGROUND: LGR5 is an important marker of intestinal stem cells and performs its
      vital functions at the cell membrane. Despite the importance of LGR5 to both
      normal and cancer stem cell biology, it is not known how microenvironmental
      stress affects the expression and subcellular distribution of the protein.
      METHODS: Nutrient stress was induced through glucose starvation. Glycosylation
      status was assessed using endoglycosidase or tunicamycin treatment. Flow
      cytometry and confocal microscopy were used to assess subcellular distribution of
      LGR5. RESULTS: Glucose deprivation altered the glycosylation status of LGR5
      resulting in reduced protein stability and cell surface expression. Furthermore,
      inhibiting LGR5 glycosylation resulted in depleted surface expression and reduced
      localisation in the cis-Golgi network. CONCLUSIONS: Nutrient stress within a
      tumour microenvironment has the capacity to alter LGR5 protein stability and
      membrane localisation through modulation of LGR5 glycosylation status. As LGR5
      surface localisation is required for enhanced Wnt signalling, this is the first
      report to show a mechanism by which the microenvironment could affect LGR5
      function.

PMID- 25611301
TI  - MicroRNA in radiotherapy: miRage or miRador?
AB  - At least half of all cancer patients will receive radiation therapy. Tumour
      radioresistance, or the failure to control certain tumours with this treatment,
      can result in locoregional recurrence; thus there is great interest in
      understanding the underlying biology and developing strategies to overcome this
      problem. The expanding investigation of microRNA in cancer suggests that these
      regulatory factors can influence the DNA damage response, the microenvironment
      and survival pathways, among other processes, and thereby may affect tumour
      radioresistance. As microRNA are readily detectable in tumours and biofluids,
      they hold promise as predictive biomarkers for therapy response and prognosis.
      This review highlights the current insights on the major ways that microRNA may
      contribute to tumour radiation response and whether their levels reflect
      treatment success. We conclude by applying the potential framework of future
      roles of miR in personalised radiotherapy using prostate cancer clinical
      management as an example. 

PMID- 25611302
TI  - OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after
      irinotecan-based chemotherapy.
AB  - BACKGROUND: Treatment of advanced and metastatic colorectal cancer with
      irinotecan is hampered by severe toxicities. The active metabolite of irinotecan,
      SN-38, is a known substrate of drug-metabolising enzymes, including UGT1A1, as
      well as OATP and ABC drug transporters. METHODS: Blood samples (n=127) and tumour
      tissue (n=30) were obtained from advanced cancer patients treated with irinotecan
      based regimens for pharmacogenetic and drug level analysis and transporter
      expression. Clinical variables, toxicity, and outcomes data were collected.
      RESULTS: SLCO1B1 521C was significantly associated with increased SN-38 exposure
      (P<0.001), which was additive with UGT1A1*28. ABCC5 (rs562) carriers had
      significantly reduced SN-38 glucuronide and APC metabolite levels. Reduced risk
      of neutropenia and diarrhoea was associated with ABCC2-24C/T (odds ratio
      (OR)=0.22, 0.06-0.85) and CES1 (rs2244613; OR=0.29, 0.09-0.89), respectively.
      Progression-free survival (PFS) was significantly longer in SLCO1B1 388G/G
      patients and reduced in ABCC2-24T/T and UGT1A1*28 carriers. Notably, higher
      OATP1B3 tumour expression was associated with reduced PFS. CONCLUSIONS:
      Clarifying the association of host genetic variation in OATP and ABC transporters
      to SN-38 exposure, toxicity and PFS provides rationale for personalising
      irinotecan-based chemotherapy. Our findings suggest that OATP polymorphisms and
      expression in tumour tissue may serve as important new biomarkers.

PMID- 25611304
TI  - From Dissertation Defense to Dissemination: Jump Start Your Academic Career With
      a Scholar Mentor Group.
AB  - PROBLEM: The dissertation provides an excellent source of scholarly productivity
      for new doctoral faculty, yet is often neglected because of the demands inherent
      in the faculty role. METHODS: The purpose of this paper is to present a case
      study of a scholar mentor group composed of three graduates of a PhD nursing
      program and their shared dissertation chair, who acted as a senior scholar mentor
      to the group. FINDINGS: By working together, we have been able to enhance our
      scholarly productivity by disseminating our dissertations through presentations
      and publications. The paper will present the evolving process of this working
      group, summarize outcomes, analyze the challenges, and provide suggestions for
      future doctoral students and faculty who are working with them. CONCLUSIONS: Our
      experience and scholar mentor model captures the best of both worlds-the benefits
      of interaction with academic peers and the benefits of having a senior scholar
      mentor. This was accomplished while all members were at different schools in
      different cities and states. Although other literatures that document successful
      collaborations using a peer-mentorship model are available, we were unable to
      locate any that documents a post-doctoral group with a senior scholar mentor who
      continued working together after graduation.

PMID- 25611303
TI  - Actin cytoskeletal control during epithelial to mesenchymal transition: focus on
      the pancreas and intestinal tract.
AB  - The formation of epithelial tissues allows organisms to specialise and form
      tissues with diverse functions and compartmentalised environments. The tight
      controls on cell growth and migration required to maintain epithelia can present
      problems such as the development and spread of cancer when normal pathways are
      disrupted. By attaining a deeper understanding of how cell migration is
      suppressed to maintain the epithelial organisation and how it is reactivated when
      epithelial tissues become mesenchymal, new insights into both cancer and
      development can be gained. Here we discuss recent developments in our
      understanding of epithelial and mesenchymal regulation of the actin cytoskeleton
      in normal and cancerous tissue, with a focus on the pancreas and intestinal
      tract. 

PMID- 25611305
TI  - Skin physiology in pruritus of advanced ageing.

PMID- 25611307
TI  - Pre-equilibration kinetic size-exclusion chromatography with mass spectrometry
      detection (peKSEC-MS) for label-free solution-based kinetic analysis of protein
      small molecule interactions.
AB  - Here we introduce pre-equilibration kinetic size-exclusion chromatography with
      mass-spectrometry detection (peKSEC-MS), which is a label-free solution-based
      kinetic approach for characterizing non-covalent protein-small molecule
      interactions. In this method, a protein and a small molecule are mixed outside
      the column and incubated to approach equilibrium. The equilibrium mixture is then
      introduced into the SEC column to initiate the dissociation process by separating
      small molecules from the complex inside the column. A numerical model of a 1
      dimensional separation was constructed to simulate mass chromatograms of the
      small molecule for varying rate constants of binding. 

PMID- 25611306
TI  - Effects of lipid composition and solution conditions on the mechanical properties
      of membrane vesicles.
AB  - The mechanical properties of cell-sized giant unilamellar liposomes were studied
      by manipulating polystyrene beads encapsulated within the liposomes using double
      beam laser tweezers. Mechanical forces were applied to the liposomes from within
      by moving the beads away from each other, which caused the liposomes to elongate.
      Subsequently, a tubular membrane projection was generated in the tip at either
      end of the liposome, or the bead moved out from the laser trap. The force
      required for liposome transformation reached maximum strength just before
      formation of the projection or the moving out of the bead. By employing this
      manipulation system, we investigated the effects of membrane lipid compositions
      and environment solutions on the mechanical properties. With increasing content
      of acidic phospholipids, such as phosphatidylglycerol or phosphatidic acid, a
      larger strength of force was required for the liposome transformation. Liposomes
      prepared with a synthetic dimyristoylphosphatidylcholine, which has uniform
      hydrocarbon chains, were transformed easily compared with liposomes prepared
      using natural phosphatidylcholine. Surprisingly, bovine serum albumin or fetuin
      (soluble proteins that do not bind to membranes) decreased liposomal membrane
      rigidity, whereas the same concentration of sucrose showed no particular effect.
      These results show that the mechanical properties of liposomes depend on their
      lipid composition and environment. 

PMID- 25611308
TI  - A randomized phase I clinical study of cis-urocanic acid eye drops in healthy
      adult subjects.
AB  - PURPOSE: To evaluate safety, ocular tolerability and pharmacokinetics of 0.5% and
      2.5% cis-urocanic acid (cis-UCA) eye drops. METHODS: In this phase I, double
      blinded, placebo-controlled trial, 37 healthy volunteers were randomized to three
      treatment arms: 0.5% cis-UCA (12 subjects), 2.5% cis-UCA (12 subjects) and
      placebo eye drops (13 subjects). In the first part, the subjects were dosed
      topically on a randomized eye with one drop three times at 7 +/- 1 hr intervals
      during 1 day. In the second part, the subjects self-administered three daily
      drops at 7 +/- 1 hr intervals on both eyes for 14 days. Physical examination of
      the eyes was performed seven times during the study. Tolerability of cis-UCA was
      assessed by ocular comfort rating questionnaire. Pharmacokinetic blood and urine
      samples were analysed under good laboratory practice (GLP). RESULTS: All subjects
      completed both parts of the study. There were no significant adverse events
      (AEs). The most common treatment-related ocular AE was eye irritation (62.2% of
      subjects). Cis-UCA concentrations in plasma remained below the limit of
      quantification (0.195 MUg/ml) in all but two subjects. The fraction of the
      administered drug excreted into urine over the total collection period ranged
      from 3.2% to 61.6% of the last dose and from 1.1% to 20.5% of the daily dose.
      CONCLUSIONS: Topical ocular administration of cis-UCA solution is safe and apart
      from mild- and short-lasting eye irritation after administration well tolerated
      in healthy adult subjects. Topical ocular dosing leads to transient systemic
      exposure to cis-UCA that does not cause systemic AEs.

PMID- 25611309
TI  - Prevalence of gastroesophageal reflux disease in children, adults, and elderly in
      the same community.
AB  - BACKGROUND AND AIM: The prevalence of gastroesophageal reflux disease (GERD) in
      adults is increasing in Japan as well as worldwide likely due to increasing
      obesity and the decreasing rate of Helicobacter pylori infection. However, data
      regarding the prevalence of GERD in children and adolescents in Japan are
      lacking. We investigated the prevalence of GERD in children, adults, and elderly
      living in the same community. METHODS: We surveyed employees of Shimane
      University Hospital and a related facility and their families using the
      Gastroesophageal Reflux Disease Questionnaire (GerdQ) and Izumo Scale instruments
      with demographic information (age, sex, body height, and body weight) and
      information regarding concurrent medication being taken for GERD. The presence of
      GERD was defined as a GerdQ score of >= 8. RESULTS: A total of 1859 subjects (771
      males, 1088 females; 6-96 years old) were eligible for assessment. The prevalence
      of GERD in those under 20 years old was 4.4%, which was approximately one third
      of the rate in adults (11.6%). GERD prevalence was closely associated with
      obesity in adults, but not in subjects under 20 years old. GERD and other
      gastrointestinal symptoms frequently overlapped in both adults and younger
      subjects. CONCLUSION: We found that the prevalence of GERD in subjects under 20
      years of age was lower than that in adults and not associated with obesity.
      Nevertheless, it is important to be aware of symptoms such as heartburn and/or
      regurgitation when children and adolescents seek routine clinical care.

PMID- 25611310
TI  - The relationship between psychosocial factors and breast cancer screening
      behaviors of older Hispanic women.
AB  - Guided by the theory of planned behavior, this study utilized data from the 2008
      wave of the Health and Retirement Study to investigate psychosocial factors
      associated with older Hispanic women's participation in breast cancer screening
      services. Hierarchical logistic regression models were used to assess the odds of
      breast cancer screening participation. Findings indicate that satisfaction with
      aging and constraints were associated with a reduced likelihood of participating
      in breast cancer screening. These findings suggest the continued importance to
      assess older women's attitudes when discussing preventive services. 

PMID- 25611311
TI  - Phenotype-genotype correlations in hemophilia A carriers are consistent with the
      binary role of the phase between F8 and X-chromosome inactivation.
AB  - BACKGROUND: The recessive X-linked disorder hemophilia A (HA) is rarely expressed
      in female carriers, most of whom express about half of normal factor VIII
      activity ( FVIII: C). OBJECTIVE: To propose an integrative assessment model for
      the binary role of the phase between the mutated F8 and the active X-chromosome
      (Xa) in FVIII: C in HA carriers. METHODS: We studied 67 females at risk of severe
      HA, comprising five symptomatic females ( FVIII: C < 1.5 IU dL(-1) ) and 14
      controls. A correlation study between FVIII: C (observed vs. expected) and X
      chromosome inactivation (XCI) patterns (XIPs; androgen receptor gene [AR] system)
      in blood leukocyte DNA was performed in carriers, by comparison of a model
      correlating FVIII: C and XIP with arbitrary models devoid of biological
      significance, and with FVIII: C levels in non-carriers (mean model) as a proxy
      from background data dispersion not influenced by XIP. RESULTS: We provide proof
      of-concept example from a family presenting with extremely skewed XIPs in which
      the severe HA phenotype appeared in a heterozygous carrier of a crossover between
      AR and F8 loci that phased the mutated F8 with the maternally inherited Xa.
      Furthermore, four cases of severe HA affected women who had a combination of a
      heterozygous F8 mutation and extremely skewed XIPs in leukocytes or oral mucosa
      are presented. Correlation analyses between FVIII: C levels and XIPs in carriers
      (n = 38) but not in non-carriers (n = 20) showed highly significant differences
      between the proposed correlation model and models without biological
      significance. The data support a binary influence of XCI, either increasing or
      decreasing the FVIII: C, subject to the underlying phase set between the F8
      mutation and XCI. CONCLUSIONS: Our evidence suggests that the phase between XCI
      and mutated F8 acts as a molecular switch conditioning FVIII: C levels and HA
      expression in carriers.

PMID- 25611312
TI  - Right and Left Atrial Dissimilarities in Normal Subjects Explored by Speckle
      Tracking Echocardiography.
AB  - BACKGROUND: Atrial function is an important contributor of ventricular function
      and has a prognostic role in various cardiovascular diseases. We tested the
      hypothesis that right and left atrial (RA & LA) function may not be equal despite
      their accommodating identical cardiac output. METHODS: Two-dimensional (2D)
      speckle tracking echocardiography was acquired from the apical four-chamber view
      in 100 normal subjects. Both RA/LA subendocardial borders were traced to obtain
      atrial volumes, strain (epsilon) and strain rate (SR). Reservoir, conduit, and
      booster pump functions were evaluated. Consequently, epsilonNeg (corresponding to
      pump function) and epsilonPos (corresponding to conduit function) were gauged.
      The SR parameters (SRLateNeg, SRPos, and SREarlyNeg), corresponding respectively
      to atrial systole, inception of ventricular systole, and inception of ventricular
      diastole, were measured. RESULTS: Mean age was 39 +/- 15 years with 50 men (50%).
      Volumetric indices revealed that reservoir (Filling Volume = 35.1 +/- 10.4 mL for
      LA vs. 27.47 +/- 11.93 mL for RA, expansion index = 52.18 +/- 16.89% for LA vs.
      45.03 +/- 16.49% for RA and diastolic emptying index = 52.85 +/- 16.85 for LA vs.
      45.62 +/- 16.5 for RA, P < 0.001) and conduit (passive emptying (%) of total
      emptying = 34.49 +/- 10.4 for LA vs. 26.82 +/- 11.98 for RA and passive emptying
      index = 52.63 +/- 16.86 for LA vs. 45.39 +/- 16.5 for RA, P < 0.001) functions
      were significantly higher in the LA compared to the RA. Nevertheless, deformation
      indices demonstrated an opposite pattern (SRpos = 1.88 +/- 0.74 for RA vs. 1.56
      +/- 0.54 for LA, P = 0.03 and epsilonPos = 59.56 +/- 30.63 for RA vs. 45.94 +/-
      16.67 for LA, P < 0.001). Reservoir, conduit, and booster pump functions showed
      no statistical significance among both genders. CONCLUSIONS: Evaluation of global
      and regional RA/LA function by speckle tracking echocardiography is feasible. The
      current report provides insights regarding dissimilarities between both atria in
      healthy individuals. The significance of these findings and their potential
      application will warrant further work.

PMID- 25611314
TI  - Injury and illness epidemiology at a summer sport-camp program, 2008 through
      2011.
AB  - CONTEXT: University-sponsored summer sport camps often employ athletic trainers;
      however, there is a dearth of epidemiologic studies describing the injury and
      illness experience of sport-camp participants to guide clinicians. OBJECTIVE: To
      describe the injury and illness experience of youth participants at a university
      sponsored summer sport-camp program during a 4-year period. DESIGN: Descriptive
      epidemiology study. SETTING: A National Collegiate Athletic Association Division
      I university that sponsored 76 to 81 camps for 28 sports each summer. PATIENTS OR
      OTHER PARTICIPANTS: A total of 44, 499 camp participants enrolled during the 4
      years. Male and female participants ranged in age from 10 to 17 years and in
      athletic skill from novice to elite. MAIN OUTCOME MEASURE(S): Data from
      handwritten injury and illness log books, maintained by sports health care
      personnel, were accessed retrospectively, entered into an electronic spreadsheet,
      and coded. Data were applied to the National Athletic Injury/Illness Reporting
      System. Participant-personnel contacts, defined as any instance when a
      participant sought health care services from personnel, were calculated per 100
      participants. Injury and illness rates were calculated per 10 ,000 exposures,
      measured in participant-days. The distribution of injury and illness conditions
      and affected body regions were calculated. RESULTS: There were 11 ,735 contacts,
      for an overall rate of 26 per 100 participants, and 4949 injuries and illnesses,
      for a rate of 1 per 10, 000 participant-days. Participants at single-sex camps
      were less likely to sustain injuries and illnesses than participants at
      coeducational camps (rate ratio [RR] = 0.49; 95% confidence interval = 0.45, 0.
      35; P < .001, and RR = 0.47; 95% confidence interval = 0.43, 0.51; P < .001,
      respectively). The lower extremity was injured most frequently (27.9%). Most
      injury and illness conditions were dermatologic (37.1%). CONCLUSIONS: The contact
      and injury and illness differences observed among sports and between sexes
      demonstrated potential differences in the sports health care needs of camp
      participants. These data can be used to make evidence-based clinical decisions,
      such as determining injury-prevention strategies and sports health care staffing
      needs.

PMID- 25611313
TI  - Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment
      for patients with carcinoma of unknown primary site: A randomized, phase 2 trial.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy of
      belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin
      in the empiric first-line treatment of patients with carcinoma of unknown primary
      site (CUP). METHODS: In this randomized phase 2 trial, previously untreated
      patients with CUP were randomized to receive belinostat plus
      paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B)
      repeated every 21 days. Patients were re-evaluated every 2 cycles, and those
      without disease progression continued treatment for 6 cycles. Patients in group A
      then continued receiving single-agent belinostat, whereas patients in group B
      stopped treatment. The primary endpoint was progression-free survival (PFS): The
      authors postulated that the addition of belinostat would improve PFS from 5
      months (expected with paclitaxel/carboplatin) to 8 months. RESULTS: In total, 89
      patients were randomized (group A, n = 44; group B, n = 45), and the demographics
      and disease characteristics were balanced between the 2 groups. The addition of
      belinostat to paclitaxel/carboplatin did not improve PFS (group A, 5.4 months
      [95% confidence interval, 3.0-6.0 months]; group B, 5.3 months [95% confidence
      interval, 2.8-6.6 months]; P = .85). Overall survival was 12.4 months for group A
      versus 9.1 months for group B (P = .20). The response rate favored the belinostat
      group (45% vs 21%; P = .02). Belinostat resulted in a modest increase in
      treatment toxicity. CONCLUSIONS: The addition of belinostat to
      paclitaxel/carboplatin did not improve the PFS of patients with CUP who were
      receiving first-line therapy, although the patients who received belinostat had a
      higher investigator-assessed response rate. Future trials in CUP should focus on
      specific subsets, defined either by the predicted tissue of origin or by the
      identification of targetable molecular abnormalities.

PMID- 25611315
TI  - The Trojan Lifetime Champions Health Survey: development, validity, and
      reliability.
AB  - CONTEXT: Self-report questionnaires are an important method of evaluating
      lifespan health, exercise, and health-related quality of life (HRQL) outcomes
      among elite, competitive athletes. Few instruments, however, have undergone
      formal characterization of their psychometric properties within this population.
      OBJECTIVE: To evaluate the validity and reliability of a novel health and
      exercise questionnaire, the Trojan Lifetime Champions (TLC) Health Survey.
      DESIGN: Descriptive laboratory study. SETTING: A large National Collegiate
      Athletic Association Division I university. PATIENTS OR OTHER PARTICIPANTS: A
      total of 63 university alumni (age range, 24 to 84 years), including former
      varsity collegiate athletes and a control group of nonathletes. INTERVENTION(S):
      Participants completed the TLC Health Survey twice at a mean interval of 23 days
      with randomization to the paper or electronic version of the instrument. MAIN
      OUTCOME MEASURE(S): Content validity, feasibility of administration, test-retest
      reliability, parallel-form reliability between paper and electronic forms, and
      estimates of systematic and typical error versus differences of clinical interest
      were assessed across a broad range of health, exercise, and HRQL measures.
      RESULTS: Correlation coefficients, including intraclass correlation coefficients
      (ICCs) for continuous variables and kappa agreement statistics for ordinal
      variables, for test-retest reliability averaged 0.86, 0.90, 0.80, and 0.74 for
      HRQL, lifetime health, recent health, and exercise variables, respectively.
      Correlation coefficients, again ICCs and kappa, for parallel-form reliability
      (ie, equivalence) between paper and electronic versions averaged 0.90, 0.85,
      0.85, and 0.81 for HRQL, lifetime health, recent health, and exercise variables,
      respectively. Typical measurement error was less than the a priori thresholds of
      clinical interest, and we found minimal evidence of systematic test-retest error.
      We found strong evidence of content validity, convergent construct validity with
      the Short-Form 12 Version 2 HRQL instrument, and feasibility of administration in
      an elite, competitive athletic population. CONCLUSIONS: These data suggest that
      the TLC Health Survey is a valid and reliable instrument for assessing lifetime
      and recent health, exercise, and HRQL, among elite competitive athletes.
      Generalizability of the instrument may be enhanced by additional, larger-scale
      studies in diverse populations.

PMID- 25611316
TI  - Analysis of morphological markers of chromosomal instability in ascitic fluid.
AB  - Chromosomal instability (CI) plays a major role in the carcinogenesis.
      Micronuclei, nuclear budding, chromatin bridges,and multipolar mitoses are the
      morphological markers of CI and have never been studied in routine cytological
      specimens. Aims of the study is to analyze the significance of morphological
      markers of CI in malignant and benign ascitic fluid smears. A total of sixty
      benign and 40 malignant ascitic fluid samples were selected for this study. All
      the cases with malignant ascitic fluid showed histopathological evidence of
      malignancy in ovary and omentum. Chromatin bridges, multipolar mitosis (MPM),
      micronuclei and nuclear budding were counted in 1000 cells in representative May
      Grunwald Giemsa (MGG) stained smears. The CI markers were correlated with the
      cytological diagnosis of effusion. The mean number of micronuclei, nuclear
      budding, chromatin bridge and multipolar mitoses found in malignant effusions
      were 13.2611.79, 10.1067.07, 2.5362.67, 1.964.5, respectively. The mean number of
      micronuclei, nuclear budding, anaphase bridges, and MPM found in benign effusion
      cases were 0.566761.07934, 0.516761.33, 0.66760.25, and 0, respectively. The
      student t test showed significant differences between malignant and benign
      ascitic fluid samples for each marker of CI. This is the first comprehensive
      study of morphological markers of CI in ascitic fluid smears. This study has
      shown strong correlation between markers of CI and cytological diagnosis of
      malignancy. In future, the knowledge of these markers can be applied to diagnose
      malignancy in suspected cases of effusion in difficult situations.

PMID- 25611317
TI  - Dissemination of a highly virulent pathogen: tracking the early events that
      define infection.
AB  - The series of events that occurs immediately after pathogen entrance into the
      body is largely speculative. Key aspects of these events are pathogen
      dissemination and pathogen interactions with the immune response as the invader
      moves into deeper tissues. We sought to define major events that occur early
      during infection of a highly virulent pathogen. To this end, we tracked early
      dissemination of Yersinia pestis, a highly pathogenic bacterium that causes
      bubonic plague in mammals. Specifically, we addressed two fundamental questions:
      (1) do the bacteria encounter barriers in disseminating to draining lymph nodes
      (LN), and (2) what mechanism does this nonmotile bacterium use to reach the LN
      compartment, as the prevailing model predicts trafficking in association with
      host cells. Infection was followed through microscopy imaging in addition to
      assessing bacterial population dynamics during dissemination from the skin. We
      found and characterized an unexpected bottleneck that severely restricts
      bacterial dissemination to LNs. The bacteria that do not pass through this
      bottleneck are confined to the skin, where large numbers of neutrophils arrive
      and efficiently control bacterial proliferation. Notably, bottleneck formation is
      route dependent, as it is abrogated after subcutaneous inoculation. Using a
      combination of approaches, including microscopy imaging, we tested the prevailing
      model of bacterial dissemination from the skin into LNs and found no evidence of
      involvement of migrating phagocytes in dissemination. Thus, early stages of
      infection are defined by a bottleneck that restricts bacterial dissemination and
      by neutrophil-dependent control of bacterial proliferation in the skin.
      Furthermore, and as opposed to current models, our data indicate an intracellular
      stage is not required by Y. pestis to disseminate from the skin to draining LNs.
      Because our findings address events that occur during early encounters of
      pathogen with the immune response, this work can inform efforts to prevent or
      control infection. 

PMID- 25611318
TI  - Histone chaperone-mediated nucleosome assembly process.
AB  - A huge amount of information is stored in genomic DNA and this stored information
      resides inside the nucleus with the aid of chromosomal condensation factors. It
      has been reported that the repeat nucleosome core particle (NCP) consists of 147
      bp of DNA and two copies of H2A, H2B, H3 and H4. Regulation of chromosomal
      structure is important to many processes inside the cell. In vivo, a group of
      histone chaperones facilitate and regulate nucleosome assembly. How NCPs are
      constructed with the aid of histone chaperones remains unclear. In this study,
      the histone chaperone-mediated nucleosome assembly process was investigated using
      single-molecule tethered particle motion (TPM) experiments. It was found that
      Asf1 is able to exert more influence than Nap1 and poly glutamate acid (PGA) on
      the nucleosome formation process, which highlights Asf1's specific role in
      tetrasome formation. Thermodynamic parameters supported a model whereby
      energetically favored nucleosomal complexes compete with non-nucleosomal
      complexes. In addition, our kinetic findings propose the model that histone
      chaperones mediate nucleosome assembly along a path that leads to enthalpy
      favored products with free histones as reaction substrates. 

PMID- 25611319
TI  - Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female
      lower genital tract.
AB  - OBJECTIVE: Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses
      at mucosal sites including in the lower genital tract. Since several types of
      bacteria produce proteases that cleave IL-8 and many types of bacteria can be
      present in lower genital tract microbiota, we assessed genital fluids for IL-8
      cleavage/alteration. STUDY DESIGN: Genital fluids collected by lavage from 200
      women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8
      cleavage/alteration by ELISA. RESULTS: IL-8 cleaving/altering activity was
      observed in fluids from both HIV-positive (28%) and HIV-negative women (35%).
      There was no clear relationship between the activity and the types of bacteria
      present in the lower genital tract as determined by high-throughput sequencing of
      the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases
      (MMPs) reduced the activity and a multiplex assay that detects both inactive and
      active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, 
      9, -10 and -12 in genital secretions from many of the women. The IL-8
      cleaving/altering activity significantly correlated with active MMP-9 as well as
      with cleavage of a substrate that is acted on by several active MMPs.
      CONCLUSIONS: These studies show that multiple MMPs are present in the genital
      tract of women and strongly suggest that MMP-9 in genital secretions can cleave
      IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL
      8 can modulate inflammatory responses in the lower genital tract.

PMID- 25611320
TI  - Reference ranges of cholesterol sub-fractions in random healthy adults in
      Ouagadougou, Burkina Faso.
AB  - In Burkina Faso, the values that serve as clinical chemistry reference ranges are
      those provided by European manufacturers' insert sheets based on reference of the
      Western population. However, studies conducted so far in some African countries
      reported significant differences in normal laboratory ranges compared with those
      of the industrialized world. The aim of this study was to determine reference
      values of cholesterol fractions in apparently normal adults in Burkina Faso that
      could be used to better assess the risks related to cardiovascular diseases.
      Study population was 279 healthy subjects aged from 15 to 50 years including 139
      men and 140 women recruited at the Regional Center of Blood Transfusion of
      Ouagadougou, capital city of Burkina Faso (West Africa). Exclusion criteria based
      on history and clinical examination were used for defining reference individuals.
      The dual-step precipitation of HDL cholesterol sub-fractions using dextran
      sulfate was performed according to the procedure described by Hirano. The medians
      were calculated and reference values were determined at 2.5th and 97.5th
      percentiles. The median and upper ranges for total cholesterol, LDL cholesterol,
      total HDL cholesterol and HDL2 cholesterol were observed to be higher in women in
      comparison to men (p <0.05). These reference ranges were similar to those derived
      from other African countries but lower than those recorded in France and in USA.
      This underscores the need for such comprehensible establishment of reference
      values for limited resources countries. Our study provides the first cholesterol
      sub-fractions (HDL2 and HDL3) reference ranges for interpretation of laboratory
      results for cardiovascular risk management in Burkina Faso. 

PMID- 25611321
TI  - Socio-economic status and motor performance of children and adolescents.
AB  - The study examines the question to what extent children and adolescents differ in
      terms of motor performance in dependence of their socio-economic status (SES). A
      sample of 1389 students in Saarland (Germany) in various grades (1st grade: age
      7.26 +/- 0.38 years, 4th grade: 10.3 +/- 0.4 years, 7th grade: 13.44 +/- 0.49
      years, 10th grade: 16.36 +/- 0.69 years) has been examined. Their motor
      performance has been measured by means of 20-m sprint, standing long jump and a 6
      minute run, and the SES by means of a parent survey. Based on the indicators
      school education, professional education, job position and household income, the
      SES was categorised in a three-step approach (low, middle, high). The influence
      on dependent variables was analysed by using multivariate analysis of variance.
      Students with a higher SES exhibit a higher motor performance compared with that
      of lower SES (results of the multivariate: Pillai's Trace = .05, F[6; 2526] =
      12.56, p = .001; [Formula: see text]). In addition, the data for students of
      higher SES differ significantly from the data of a German reference sample
      (higher motor performance compared with standard values). In contrast, persons of
      lower SES do not differ from the reference sample, and those of middle SES differ
      only slightly from the reference sample. The results are relevant when
      considering specific prevention efforts concerning motor performance of certain
      groups. Especially those institutions and schools should be focused upon whose
      catchment area includes a high share of socially disadvantaged population groups.

PMID- 25611322
TI  - LATERAL ORGAN BOUNDARIES DOMAIN (LBD)10 interacts with SIDECAR POLLEN/LBD27 to
      control pollen development in Arabidopsis.
AB  - During male gametophyte development in Arabidopsis thaliana, the microspores
      undergo an asymmetric division to produce a vegetative cell and a generative
      cell, which undergoes a second division to give rise to two sperm cells. SIDECAR
      POLLEN/LATERAL ORGAN BOUNDARIES DOMAIN (LBD) 27 plays a key role in the
      asymmetric division of microspores. Here we provide molecular genetic evidence
      that a combinatorial role of LBD10 with LBD27 is crucial for male gametophyte
      development in Arabidopsis. Expression analysis, genetic transmission and pollen
      viability assays, and pollen development analysis demonstrated that LBD10 plays a
      role in the male gametophyte function primarily at germ cell mitosis. In the
      mature pollen of lbd10 and lbd10 expressing a dominant negative version of LBD10,
      LBD10:SRDX, aberrant microspores such as bicellular and smaller tricellular
      pollen appeared at a ratio of 10-15% with a correspondingly decreased ratio of
      normal tricellular pollen, whereas in lbd27 mutants, 70% of the pollen was
      aborted. All pollen in the lbd10 lbd27 double mutants was aborted and severely
      shrivelled compared with that of the single mutants, indicating that LBD10 and
      LBD27 are essential for pollen development. Gene expression and subcellular
      localization analyses of LBD10:GFP and LBD27:RFP during pollen development
      indicated that posttranscriptional and/or posttranslational controls are involved
      in differential accumulation and subcellular localization of LBD10 and LBD27
      during pollen development, which may contribute in part to combinatorial and
      distinct roles of LBD10 with LBD27 in microspore development. In addition, we
      showed that LBD10 and LBD27 interact to form a heterodimer for nuclear
      localization. 

PMID- 25611323
TI  - Income-related inequalities in inadequate dentition over time in Australia,
      Brazil and USA adults.
AB  - OBJECTIVE: To assess changes over time of the absolute and relative household
      income-related inequalities in inadequate dentition (ID) among Australians,
      Brazilians and USA adults. METHODS: This study used nationwide oral health survey
      data from Australia (n = 1200 in 1999; n = 2729 in 2005), Brazil (n = 13 431 in
      2003; n = 9779 in 2010) and USA (n = 2542 in 1999; n = 1596 in 2005). Absolute
      income inequalities were calculated using Absolute Concentration Index (ACI) and
      Slope Index of Inequality (SII), while relative inequalities were calculated
      using Relative Concentration Index (RCI) and Relative Index of Inequality (RII).
      RESULTS: Prevalence of ID in the studied period dropped from 8.7% to 3.1% in
      Australia; from 42.1% to 22.4% in Brazil; and remained stable in USA, nearly
      8.0%. Absolute income inequalities were highest in Brazil, followed by the USA
      and Australia; relative inequalities were lower in Brazil than in Australia and
      the USA. ID was higher among Brazilian females (2010) and for the poorest group
      in all countries and periods. A remarkable reduction in absolute inequalities
      were found in Australia [Slope Index of Inequality (SII) and AIC 60%] and in
      Brazil (SII 25%; ACI 33%) while relative inequalities increased both in Australia
      (RCI and RII 40%) and in Brazil (RCI 24%; RII 38%). No changes in absolute and
      relative income inequalities were found in the USA. CONCLUSION: There were still
      persistent absolute and relative income inequalities in ID in all examined
      countries. There has been a reduction in absolute income inequalities in ID but
      an increase in relative income inequalities.

PMID- 25611324
TI  - A combined light sheet fluorescence and differential interference contrast
      microscope for live imaging of multicellular specimens.
AB  - We describe a microscope capable of both light sheet fluorescence microscopy and
      differential interference contrast microscopy (DICM). The two imaging modes,
      which to the best of our knowledge have not previously been combined, are
      complementary: light sheet fluorescence microscopy provides three-dimensional
      imaging of fluorescently labelled components of multicellular systems with high
      speed, large fields of view, and low phototoxicity, whereas differential
      interference contrast microscopy reveals the unlabelled neighbourhood of tissues,
      organs, and other structures with high contrast and inherent optical sectioning.
      Use of a single Nomarski prism for differential interference contrast microscopy
      and a shared detection path for both imaging modes enables simple integration of
      the two techniques in one custom microscope. We provide several examples of the
      utility of the resulting instrument, focusing especially on the digestive tract
      of the larval zebrafish, revealing in this complex and heterogeneous environment
      anatomical features, the behaviour of commensal microbes, immune cell motions,
      and more. 

PMID- 25611325
TI  - Bees under stress: sublethal doses of a neonicotinoid pesticide and pathogens
      interact to elevate honey bee mortality across the life cycle.
AB  - Microbial pathogens are thought to have a profound impact on insect populations.
      Honey bees are suffering from elevated colony losses in the northern hemisphere
      possibly because of a variety of emergent microbial pathogens, with which
      pesticides may interact to exacerbate their impacts. To reveal such potential
      interactions, we administered at sublethal and field realistic doses one
      neonicotinoid pesticide (thiacloprid) and two common microbial pathogens, the
      invasive microsporidian Nosema ceranae and black queen cell virus (BQCV),
      individually to larval and adult honey bees in the laboratory. Through fully
      crossed experiments in which treatments were administered singly or in
      combination, we found an additive interaction between BQCV and thiacloprid on
      host larval survival likely because the pesticide significantly elevated viral
      loads. In adult bees, two synergistic interactions increased individual
      mortality: between N. ceranae and BQCV, and between N. ceranae and thiacloprid.
      The combination of two pathogens had a more profound effect on elevating adult
      mortality than N. ceranae plus thiacloprid. Common microbial pathogens appear to
      be major threats to honey bees, while sublethal doses of pesticide may enhance
      their deleterious effects on honey bee larvae and adults. It remains an open
      question as to whether these interactions can affect colony survival. 

PMID- 25611328
TI  - Photopatterning of cross-linkable epoxide-functionalized block copolymers and
      dual-tone nanostructure development for fabrication across the nano- and
      microscales.
AB  - The self-assembly of block copolymers in thin films provides an attractive
      approach to patterning 5-100 nm structures. Cross-linking and photopatterning of
      the self-assembled block copolymer morphologies provide further opportunities to
      structure such materials for lithographic applications, and to also enhance the
      thermal, chemical, or mechanical stability of such nanostructures to achieve
      robust templates for subsequent fabrication processes. Here, model lamellar
      forming diblock copolymers of polystyrene and poly(methyl methacrylate) with an
      epoxide functionality are synthesized by atom transfer radical polymerization. We
      demonstrate that self-assembly and cross-linking of the reactive block copolymer
      materials in thin films can be decoupled into distinct, controlled process steps
      using solvent annealing and thermal treatment/ultraviolet exposure, respectively.
      Conventional optical lithography approaches can also be applied to the cross
      linkable block copolymer materials in thin films and enable simultaneous
      structure formation across scales-micrometer scale patterns achieved by
      photolithography and nanostructures via self-assembly of the block copolymer.
      Such materials and processes are thus shown to be capable of self-assembling
      distinct block copolymers (e.g., lamellae of significantly different periodicity)
      in adjacent regions of a continuous thin film. 

PMID- 25611326
TI  - Hydrogen exchange of disordered proteins in Escherichia coli.
AB  - A truly disordered protein lacks a stable fold and its backbone amide protons
      exchange with solvent at rates predicted from studies of unstructured peptides.
      We have measured the exchange rates of two model disordered proteins, FlgM and
      alpha-synuclein, in buffer and in Escherichia coli using the NMR experiment,
      SOLEXSY. The rates are similar in buffer and cells and are close to the rates
      predicted from data on small, unstructured peptides. This result indicates that
      true disorder can persist inside the crowded cellular interior and that weak
      interactions between proteins and macromolecules in cells do not necessarily
      affect intrinsic rates of exchange. 

PMID- 25611327
TI  - Blueberries improve glucose tolerance without altering body composition in obese
      postmenopausal mice.
AB  - OBJECTIVE: Metabolic syndrome (MetS) risk increases significantly during
      menopause and remains elevated postmenopause. Several botanicals, including
      blueberries (BB), have been shown to delay MetS progression, but few studies have
      been conducted in postmenopausal animal models. Here, the effects of BB
      supplementation on obese postmenopausal mice using a chemically induced menopause
      model were examined. METHODS: After induction of menopause, mice were fed a high
      fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body
      weight and body composition were measured, and mice were subjected to glucose and
      insulin tolerance tests. Serum triglycerides and adiponectin were measured, and
      liver histology and hepatic gene expression were assessed. RESULTS: Menopausal
      and BB-supplemented mice had significantly higher body weights and fat mass than
      control mice, while menopausal mice had impaired glucose tolerance and higher
      serum triglycerides when compared with control and BB-supplemented mice.
      Menopausal mice also had hepatic steatosis that was prevented by BB
      supplementation and correlated with expression of genes involved in hepatic fatty
      acid oxidation. CONCLUSIONS: BB supplementation prevents the glucose intolerance
      and hepatic steatosis that occur in obese postmenopausal mice, and these effects
      are independent of body weight.

PMID- 25611329
TI  - Persistently elevated abnormal B-cell subpopulations and anti-core antibodies in
      patients co-infected with HIV/HCV who relapse.
AB  - Hepatitis C (HCV) treatment for patients coinfected with human immunodeficiency
      virus (HIV) and HCV is associated with modest rates of sustained virologic
      response (SVR) and an increased rate of relapse when compared to HCV monoinfected
      patients. As patients who attain SVR and patients who relapse are clinically
      indistinguishable during treatment, where both groups have fully suppressed HCV
      viral load, it has not been possible to identify in advance those who will
      relapse. Biomarkers that may distinguish patients with differential treatment
      response may be clinically useful and provide insight into mechanisms of relapse.
      In this retrospective study, serum and PBMCs were obtained from 41 HIV/HCV co
      infected patients and 17 healthy volunteers. Changes in antibody titers to
      various regions of the HCV proteome during treatment for HCV were determined
      using a novel luciferase immunoprecipitation assay. Changes in B-cell subtypes in
      patients with differential treatment response as well as healthy volunteers were
      compared. This study demonstrates that elevated anti-HCV core antibody titers
      persisted during HCV treatment in patients who relapsed when compared to those
      who attained SVR. Furthermore, characterization of B cells in patients who
      relapsed demonstrated an abnormal B-cell phenotype distribution characterized by
      elevated frequencies of exhausted B cells among relapsers at baseline, which
      persisted despite suppression of HCV viremia at 24 weeks, along with increased
      frequencies of plasmablasts. These data suggest that anti-HCV specific B cells
      may be responding to ongoing subclinical HCV replication in patients who will
      relapse.

PMID- 25611330
TI  - Study of tamoxifen urinary metabolites in rat by ultra-high-performance liquid
      chromatography time-of-flight mass spectrometry.
AB  - Tamoxifen (TMX) is a nonsteroidal estrogen antagonist drug used for the treatment
      of breast cancer. It is also included in the list of banned substances of the
      World Anti Doping Agency (WADA) prohibited in and out of competition. In this
      work, the excretion of urinary metabolites of TMX after a single therapeutic dose
      administration in rats has been studied using ultra-high-performance liquid
      chromatography electrospray time-of-flight mass spectrometry (UHPLC-TOFMS). A
      systematic strategy based on the search of typical biotransformations that a
      xenobiotic can undergo in living organisms, based on their corresponding
      molecular formula modification and accurate mass shifts, was applied for the
      identification of TMX metabolites. Prior to UHPLC-TOFMS analyses, a solid-phase
      extraction step with polymeric cartridges was applied to urine samples. Up to 38
      TMX metabolites were detected. Additional collision induced dissociation (CID)
      MS/MS fragmentation was performed using UHPLC-QTOFMS. Compared with recent
      previous studies in human urine and plasma, new metabolites have been reported
      for the first time in urine. Metabolites identified in rat urine include the
      oxygen addition, owing to different possibilities for the hydroxylation of the
      rings in different positions (m/z 388.2271), the incorporation of two oxygen
      atoms (m/z 404.2220) (including dihydroxylated derivatives or alternatives such
      as epoxidation plus hydroxylation or N-oxidation and hydroxylation), epoxide
      formation or hydroxylation and dehydrogenation [m/z 386.2114 (+O -H2 )],
      hydroxylation of the ring accompanied by N-desmethylation (m/z 374.2115),
      combined hydroxylation and methoxylation (m/z 418.2377), desaturated TMX derivate
      (m/z 370.2165) and its N-desmethylated derivate (m/z 356.2009), the two latter
      modifications not previously being reported in urine. These findings confirm the
      usefulness of the proposed approach based on UHPLC-TOFMS.

PMID- 25611332
TI  - Glycerol salicylate-based containing alpha-tricalcium phosphate as a bioactive
      root canal sealer.
AB  - The use of bioactive materials instead of inert materials to fill the root canal
      space could be an effective approach to achieve a hermetic seal and stimulate the
      healing of periapical tissues. The purpose of this study was to develop and
      characterize an endodontic sealer based on a glycerol salicylate resin and alpha
      tricalcium phosphate (alphaTCP) at physical and chemical properties. Different
      sealers were formulated using 70% of a glycerol salicylate resin and 30% of a
      mixture of calcium hydroxide and alphaTCP (0, 5, 10, or 15%, in weight). Sealers
      formulated were characterized based on setting time, in vitro degradation over
      time, pH, cytotoxicity, and mineral deposition. Sealers presented setting time
      ranging from 240 to 405 min, and basic pH over 8.21 after 28 days. Higher
      alphaTCP concentration leads to sealers with low solubility. Cell viability after
      48 h in direct contact with sealers was similar to a commercial sealer used as
      reference. The 10% and 15% alphaTCP sealers exhibited a calcium-phosphate layer
      on the surface after immersion in water and SBF for 7 days. Glycerol salicylate
      sealers with 10% and 15% alpha-tricalcium phosphate showed reliable physical
      chemical properties and apatite-forming ability.

PMID- 25611331
TI  - Distribution and frequencies of post-transcriptional modifications in tRNAs.
AB  - Functional tRNA molecules always contain a wide variety of post-transcriptionally
      modified nucleosides. These modifications stabilize tRNA structure, allow for
      proper interaction with other macromolecules and fine-tune the decoding of mRNAs
      during translation. Their presence in functionally important regions of tRNA is
      conserved in all domains of life. However, the identities of many of these
      modified residues depend much on the phylogeny of organisms the tRNAs are found
      in, attesting for domain-specific strategies of tRNA maturation. In this work we
      present a new tool, tRNAmodviz web server (http://genesilico.pl/trnamodviz) for
      easy comparative analysis and visualization of modification patterns in
      individual tRNAs, as well as in groups of selected tRNA sequences. We also
      present results of comparative analysis of tRNA sequences derived from 7
      phylogenetically distinct groups of organisms: Gram-negative bacteria, Gram
      positive bacteria, cytosol of eukaryotic single cell organisms, Fungi and
      Metazoa, cytosol of Viridiplantae, mitochondria, plastids and Euryarchaeota.
      These data update the study conducted 20 y ago with the tRNA sequences available
      at that time. 

PMID- 25611333
TI  - A critical evaluation of the clinical evidence for pomegranate preparations in
      the prevention and treatment of cardiovascular diseases.
AB  - This study attempts a critical evaluation of the clinical evidence behind the use
      of dietary pomegranate preparations in the prevention and treatment of
      cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228
      references, which yielded extractable data from 24 clinical studies of
      pomegranate preparations. Hand searching identified two further studies. The
      quality of the studies and evidence of effectiveness of pomegranate were assessed
      by an established set of conventional criteria. Overall, the study quality was
      poor. Even in the best studies, indications of benefit did not reach the
      conventional levels of statistical significance. The only study with a definitive
      design had a biochemical rather than a clinical endpoint: it showed the expected
      difference in blood concentrations of myeloperoxidase after a single dose of
      either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on
      the amounts of co-active ingredients in the preparations that were consumed by
      the subjects. If pomegranate has a role in the prevention and treatment of
      cardiovascular diseases, there is a pressing need for dose-finding and long-term
      confirmatory studies. The ultimate endpoint for definitive studies would be
      mortality, but reductions in blood pressure or demonstrable decreases in
      atherosclerotic plaques would be useful surrogates. Sample sizes for various
      assumptions are provided. Future studies need to prove the clinical benefit.

PMID- 25611334
TI  - Identifying the crystalline orientation of black phosphorus using angle-resolved
      polarized Raman spectroscopy.
AB  - An optical anisotropic nature of black phosphorus (BP) is revealed by angle
      resolved polarized Raman spectroscopy (ARPRS), and for the first time, an all
      optical method was realized to identify the crystal orientation of BP sheets,
      that is, the zigzag and armchair directions. We found that Raman intensities of
      Ag(1), B2g, and Ag(2) modes of BP not only depend on the polarization angle
      alpha, but also relate to the sample rotation angle theta. Furthermore, their
      intensities reach the local maximum or minimum values when the crystalline
      orientation is along with the polarization direction of scattered light (es).
      Combining with the angle-resolved conductance, it is confirmed that Ag(2) mode
      intensity achieves a relative larger (or smaller) local maximum under parallel
      polarization configuration when armchair (or zigzag) direction is parallel to es.
      Therefore, ARPRS can be used as a rapid, precise, and nondestructive method to
      identify the crystalline orientation of BP layers.

PMID- 25611335
TI  - Office surgery for paranasal sinus recirculation.
AB  - BACKGROUND: Circular flow of mucus between adjacent openings of a single
      paranasal sinus is known as recirculation, and can cause persistent sinonasal
      symptoms. Removing the bridging tissues allows the surgical ostium to connect to
      the natural ostium. This procedure prevents the circular flow between the 2
      ostia, and allows the mucociliary system to provide for physiologic drainage of
      the sinuses. Traditionally this has taken place in the operating room; however,
      performing this procedure in the office is possible, even when there is
      significant intervening bone. Here we report a series patients with recirculation
      successfully treated in the office. METHODS: A prospective study of 10 patients
      endoscopically diagnosed with recirculation, 9 involving the maxillary sinus and
      1 involving the sphenoid. Symptoms included facial pressure, mucus stasis,
      congestion, and recurrent sinusitis. All patients had previous sinus surgery. All
      patients were treated in the office under topical +/- local anesthesia. The
      bridging tissues between ostia were removed, 6 of which consisted of mucosal
      bands within the middle meatus, 1 with mucosa and intervening bone within the
      middle meatus, 2 with mucosa and inferior turbinate bone between ostia in the
      inferior and middle meatus, and 1 involving bone of the face of the sphenoid
      sinus. RESULTS: All 10 patients had significant improvement or resolution of the
      symptoms associated with recirculation, with no further endoscopic evidence of
      mucus recirculation. CONCLUSION: This case series demonstrates that mucus
      recirculation can be successfully treated in the office setting, even across bony
      structures. This leads to significant savings to the healthcare system and less
      missed work/school compared to an operating room procedure.

PMID- 25611336
TI  - The European Initiative ProYouth for the promotion of mental health and the
      prevention of eating disorders screening results in Hungary.
AB  - OBJECTIVE: The ProYouth programme focuses on the promotion of mental health and
      the prevention of eating disorders (EDs) among young people. The aim of our study
      was to explore whether the programme can address individuals who are at risk for
      developing 2EDs. METHOD: This study is designed as an online cross-sectional
      survey (n = 664, 12.2% men, 87.8% women, mean age: 24.9 years, SD = 5.4 years,
      range: 18-40 years). Measures included demographic data, self-reported weight and
      height, the Patient Health Questionnaire for Depression and Anxiety, Short
      Evaluation of Eating Disorders, Weight Concerns Scale and previous/current
      treatment for EDs. RESULTS: In terms of severity of EDs, 22.9% (n = 152) of the
      screened participants were symptom free, 48.8% (n = 324) had considerable
      concerns about their weight, 11.1% (n = 74) were slightly impaired, 15.1% (n =
      100) had severe impairment and 2.1% (n = 14) of participants are currently under
      treatment for EDs. In total, 56.3% of users (n = 374) registered in the
      programme. According to our results, those who had considerable concerns about
      their weight and individuals who were severely impaired registered with a greater
      odds to the programme than those who were symptom free [odds ratio (OR) = 1.64, p
      = .021 and OR = 1.90, p = .023, respectively]. Furthermore, those who previously
      received treatment for their ED registered to the programme with greater odds
      than those who did not (OR = 2.40, p = .017). CONCLUSION: ProYouth successfully
      addressed those who have elevated concerns about their weight and who also
      registered with greater odds to the programme than those who were symptom free
      regarding EDs. The screening results show that there is a greater need for
      specialized care targeting EDs in Hungary than what is currently available.

PMID- 25611337
TI  - Triple negative breast cancer: a multi-omics network discovery strategy for
      candidate targets and driving pathways.
AB  - Triple negative breast cancer (TNBC) represents approximately 15% of breast
      cancers and is characterized by lack of expression of both estrogen receptor (ER)
      and progesterone receptor (PR), together with absence of human epidermal growth
      factor 2 (HER2). TNBC has attracted considerable attention due to its
      aggressiveness such as large tumor size, high proliferation rate, and metastasis.
      The absence of clinically efficient molecular targets is of great concern in
      treatment of patients with TNBC. In light of the complexity of TNBC, we applied a
      systematic and integrative transcriptomics and interactomics approach utilizing
      transcriptional regulatory and protein-protein interaction networks to discover
      putative transcriptional control mechanisms of TNBC. To this end, we identified
      TNBC-driven molecular pathways such as the Janus kinase-signal transducers, and
      activators of transcription (JAK-STAT) and tumor necrosis factor (TNF) signaling
      pathways. The multi-omics molecular target and biomarker discovery approach
      presented here can offer ways forward on novel diagnostics and potentially help
      to design personalized therapeutics for TNBC in the future. 

PMID- 25611338
TI  - A "body armor" of leukemia cutis.

PMID- 25611339
TI  - Effect of Salted Ice Bags on Surface and Intramuscular Tissue Cooling and
      Rewarming Rates.
AB  - CONTEXT: Many researchers have investigated the effectiveness of different
      cryotherapy agents at decreasing intramuscular tissue temperatures. However, no
      one has looked at the effectiveness of adding salt to an ice bag. OBJECTIVE: To
      compare the cooling effectiveness of different ice bags (wetted, salted cubed,
      and salted crushed) on cutaneous and intramuscular temperatures. DESIGN: Repeated
      measures counterbalanced design. SETTING: University research laboratory.
      PARTICIPANTS: 24 healthy participants (13 men, 11 women; age 22.46 +/- 2.33 y,
      height 173.25 +/- 9.78 cm, mass 74.51 +/- 17.32 kg, subcutaneous thickness 0.63
      +/- 0.27 cm) with no lower-leg injuries, vascular diseases, sensitivity to cold,
      compromised circulation, or chronic use of NSAIDs. INTERVENTIONS: Ice bags made
      of wetted ice (2000 mL ice and 300 mL water), salted cubed ice (intervention A;
      2000 mL of cubed ice and 1/2 tablespoon of salt), and salted crushed ice
      (intervention B; 2000 mL of crushed ice and 1/2 tablespoon of salt) were applied
      to the posterior gastrocnemius for 30 min. Each participant received all
      conditions with at least 4 d between treatments. MAIN OUTCOME MEASURE: Cutaneous
      and intramuscular (2 cm plus adipose thickness) temperatures of nondominant
      gastrocnemius were measured during a 10-min baseline period, a 30-min treatment
      period, and a 45-min rewarming period. RESULTS: Differences from baseline were
      observed for all treatments. The wetted-ice and salted-cubed-ice bags produced
      significantly lower intramuscular temperatures than the salted-crushed-ice bag.
      Wetted-ice bags produced the greatest temperature change for cutaneous tissues.
      CONCLUSIONS: Wetted- and salted-cubed-ice bags were equally effective at
      decreasing intramuscular temperature at 2 cm subadipose. Clinical practicality
      may favor salted-ice bags over wetted-ice bags.

PMID- 25611340
TI  - Influence of vascular normalization on interstitial flow and delivery of
      liposomes in tumors.
AB  - Elevated interstitial fluid pressure is one of the barriers of drug delivery in
      solid tumors. Recent studies have shown that normalization of tumor vasculature
      by anti-angiogenic factors may improve the delivery of conventional cytotoxic
      drugs, possibly by increasing blood flow, decreasing interstitial fluid pressure,
      and enhancing the convective transvascular transport of drug molecules. Delivery
      of large therapeutic agents such as nanoparticles and liposomes might also
      benefit from normalization therapy since their transport depends primarily on
      convection. In this study, a mathematical model is presented to provide
      supporting evidence that normalization therapy may improve the delivery of 100 nm
      liposomes into solid tumors, by both increasing the total drug extravasation and
      providing a more homogeneous drug distribution within the tumor. However these
      beneficial effects largely depend on tumor size and are stronger for tumors
      within a certain size range. It is shown that this size effect may persist under
      different microenvironmental conditions and for tumors with irregular margins or
      heterogeneous blood supply.

PMID- 25611341
TI  - Effect of range of motion on aerobic capacity in adults with cerebral palsy.
AB  - The aim of the study was to examine the relationship between whole body range of
      motion (ROM) and aerobic capacity based on the fact that motor ability is closely
      related to ROM in adults with cerebral palsy (CP). The subjects were ambulant
      adults with CP (N=56). Their age, height, weight, and BMI were 36.4+/-9.2 years,
      162.6+/-9.5 cm, 58.9+/-11.0 kg, and 22.2+/-3.4 kg.m (- 2), respectively. Active
      ROM (AROM) was measured in this study. Measurements included 25 AROMs of the
      cervical spine, shoulder, elbow, wrist, hip, knee, and ankle. Peak oxygen uptake
      (VO2peak) was measured during a maximal treadmill test. Correlation analysis
      revealed that shoulder abduction and hip abduction were significantly associated
      with many other AROMs. Many AROMs including the cervical spine (rotation),
      shoulder (flexion, extension, and abduction), hip (internal rotation, external
      rotation, abduction and adduction), knee (flexion) and ankle (dorsiflexion and
      plantarflexion) were significantly correlated with VO2peak (p<0.05). The highest
      correlation coefficient was observed in the relationship between ankle
      dorsiflexion and VO2peak (p<0.01). Ankle dorsiflexion and cervical rotation of
      AROMs were maintained within the regression model of factors associated with
      VO2peak. The present study demonstrated a strong relationship between ankle
      dorsiflexion and cervical rotation of AROMs and VO2peak in ambulant adults with
      CP.

PMID- 25611343
TI  - Artificial photosynthesis of C1-C3 hydrocarbons from water and CO2 on titanate
      nanotubes decorated with nanoparticle elemental copper and CdS quantum dots.
AB  - The conversion of CO2 and water into value-added fuels with visible light is
      difficult to achieve in inorganic photocatalytic systems. However, we synthesized
      a ternary catalyst, CdS/(Cu-TNTs), which is assembled on a core of sodium
      trititanate nanotubes (TNTs; NaxH2-xTi3O7) decorated with elemental copper
      deposits followed by an overcoat of CdS quantum dot deposits. This ternary
      photocatalyst is capable of catalyzing the conversion of CO2 and water into C1-C3
      hydrocarbons (e.g., CH4, C2H6, C3H8, C2H4, C3H6) upon irradiation with visible
      light above 420 nm. With this composite photocatalyst, sacrificial electron
      donors are not required for the photoreduction of CO2. We have shown that water
      is the principal photoexcited-state electron donor, while CO2 bound to the
      composite surface serves as the corresponding electron acceptor. If the
      photochemical reaction is carried out under an atmosphere of 99.9% (13)CO2, then
      the product hydrocarbons are built upon a (13)C backbone. However, free molecular
      H2 is not observed over 5 h of visible light irradiation even though proton
      reduction in aqueous solution is thermodynamically favored over CO2 reduction. In
      terms of photocatalytic efficiency, the stoichiometric fraction of Na(+) in TNTs
      appears to be an important factor that influences the formation of the observed
      hydrocarbons. The coordination of CO2 to surface exchange sites on the ternary
      catalyst leads to the formation of surface-bound CO2 and related carbonate
      species. It appears that the bidentate binding of O?C?O to certain reactive
      surface sites reduces the energy barrier for conduction band electron transfer to
      CO2. The methyl radical (CH3(*)), an observed intermediate in the reaction, was
      positively identified using an ESR spin trapping probe molecule. The copper
      deposits on the surface of TNTs appear to play a major role in the transient
      trapping of methyl radical, which in turn self-reacts to produce ethane. 

PMID- 25611342
TI  - A molecular basis for the differential roles of Bub1 and BubR1 in the spindle
      assembly checkpoint.
AB  - The spindle assembly checkpoint (SAC) monitors and promotes kinetochore
      microtubule attachment during mitosis. Bub1 and BubR1, SAC components, originated
      from duplication of an ancestor gene. Subsequent sub-functionalization
      established subordination: Bub1, recruited first to kinetochores, promotes
      successive BubR1 recruitment. Because both Bub1 and BubR1 hetero-dimerize with
      Bub3, a targeting adaptor for phosphorylated kinetochores, the molecular basis
      for such sub-functionalization is unclear. We demonstrate that Bub1, but not
      BubR1, enhances binding of Bub3 to phosphorylated kinetochores. Grafting a short
      motif of Bub1 onto BubR1 promotes Bub1-independent kinetochore recruitment of
      BubR1. This gain-of-function BubR1 mutant cannot sustain a functional checkpoint.
      We demonstrate that kinetochore localization of BubR1 relies on direct hetero
      dimerization with Bub1 at a pseudo-symmetric interface. This pseudo-symmetric
      interaction underpins a template-copy relationship crucial for kinetochore
      microtubule attachment and SAC signaling. Our results illustrate how gene
      duplication and sub-functionalization shape the workings of an essential
      molecular network. 

PMID- 25611345
TI  - Micropatterned nanostructures: a bioengineered approach to mass-produce
      functional myocardial grafts.
AB  - Cell-based therapies are a recently established path for treating a wide range of
      human disease. Tissue engineering of contractile heart muscle for replacement
      therapy is among the most exciting and important of these efforts. However,
      current in vitro techniques of cultivating functional mature cardiac grafts have
      only been moderately successful due to the poor capability of traditional two
      dimensional cell culture systems to recapitulate necessary in vivo conditions. In
      this issue, Kiefer et al introduce a laser-patterned nanostructured substrate
      (Al/Al2O3 nanowires) for efficient maintenance of oriented human cardiomyocytes,
      with great potential to open new roads to mass-production of contractile
      myocardial grafts for cardiovascular tissue engineering.

PMID- 25611344
TI  - Selection for territory acquisition is modulated by social network structure in a
      wild songbird.
AB  - The social environment may be a key mediator of selection that operates on
      animals. In many cases, individuals may experience selection not only as a
      function of their phenotype, but also as a function of the interaction between
      their phenotype and the phenotypes of the conspecifics they associate with. For
      example, when animals settle after dispersal, individuals may benefit from
      arriving early, but, in many cases, these benefits will be affected by the
      arrival times of other individuals in their local environment. We integrated a
      recently described method for calculating assortativity on weighted networks,
      which is the correlation between an individual's phenotype and that of its
      associates, into an existing framework for measuring the magnitude of social
      selection operating on phenotypes. We applied this approach to large-scale data
      on social network structure and the timing of arrival into the breeding area over
      three years. We found that late-arriving individuals had a reduced probability of
      breeding. However, the probability of breeding was also influenced by
      individuals' social networks. Associating with late-arriving conspecifics
      increased the probability of successfully acquiring a breeding territory. Hence,
      social selection could offset the effects of nonsocial selection. Given parallel
      theoretical developments of the importance of local network structure on
      population processes, and increasing data being collected on social networks in
      free-living populations, the integration of these concepts could yield
      significant insights into social evolution. 

PMID- 25611346
TI  - Sequential en face spectral-domain optical coherence tomographic analysis of
      macular hole formation.

PMID- 25611347
TI  - Quinofuracins A-E, produced by the fungus Staphylotrichum boninense PF1444, show
      p53-dependent growth suppression.
AB  - Quinofuracins A-E, novel anthraquinone derivatives containing beta-D
      galactofuranose that were isolated from the fungus Staphylotrichum boninense
      PF1444, induced p53-dependent cell death in human tumor cells. The structures of
      quinofuracins A-E, including absolute configurations, were elucidated by
      extensive spectroscopic analysis and chemical transformation studies.
      Quinofuracins were classified into three groups according to the aglycone
      moieties. 5'-Oxoaverantin was present in quinofuracins A-C, whereas averantin and
      versicolorin B were identified in quinofuracins D and E, respectively. These
      quinofuracins induced p53-dependent growth suppression in human glioblastoma
      LNZTA3 cells.

PMID- 25611348
TI  - Noble metal aerogels-synthesis, characterization, and application as
      electrocatalysts.
AB  - CONSPECTUS: Metallic and catalytically active materials with high surface area
      and large porosity are a long-desired goal in both industry and academia. In this
      Account, we summarize the strategies for making a variety of self-supported noble
      metal aerogels consisting of extended metal backbone nanonetworks. We discuss
      their outstanding physical and chemical properties, including their three
      dimensional network structure, the simple control over their composition, their
      large specific surface area, and their hierarchical porosity. Additionally, we
      show some initial results on their excellent performance as electrocatalysts
      combining both high catalytic activity and high durability for fuel cell
      reactions such as ethanol oxidation and the oxygen reduction reaction (ORR).
      Finally, we give some hints on the future challenges in the research area of
      metal aerogels. We believe that metal aerogels are a new, promising class of
      electrocatalysts for polymer electrolyte fuel cells (PEFCs) and will also open
      great opportunities for other electrochemical energy systems, catalysis, and
      sensors. The commercialization of PEFCs encounters three critical obstacles,
      viz., high cost, insufficient activity, and inadequate long-term durability.
      Besides others, the sluggish kinetics of the ORR and alcohol oxidation and
      insufficient catalyst stability are important reasons for these obstacles.
      Various approaches have been taken to overcome these obstacles, e.g., by
      controlling the catalyst particle size in an optimized range, forming
      multimetallic catalysts, controlling the surface compositions, shaping the
      catalysts into nanocrystals, and designing supportless catalysts with extended
      surfaces such as nanostructured thin films, nanotubes, and porous nanostructures.
      These efforts have produced plenty of excellent electrocatalysts, but the
      development of multisynergetic functional catalysts exhibiting low cost, high
      activity, and high durability still faces great challenges. In this Account, we
      demonstrate that the sol-gel process represents a powerful "bottom-up" strategy
      for creating nanostructured materials that tackles the problems mentioned above.
      Aerogels are unique solid materials with ultralow densities, large open pores,
      and ultimately high inner surface areas. They magnify the specific properties of
      nanomaterials to the macroscale via self-assembly, which endow them with superior
      properties. Despite numerous investigations of metal oxide aerogels, the
      investigation of metal aerogels is in the early stage. Recently, aerogels
      including Fe, Co, Ni, Sn, and Cu have been obtained by nanosmelting of hybrid
      polymer-metal oxide aerogels. We report here exclusively on mono-, bi- and
      multimetallic noble metal aerogels consisting of Ag, Au, Pt, and Pd and their
      application as electrocatalysts.

PMID- 25611349
TI  - Effects of verb familiarity on finiteness marking in children with specific
      language impairment.
AB  - PURPOSE: Children with specific language impairment (SLI) have known deficits in
      the verb lexicon and finiteness marking. This study investigated a potential
      relationship between these 2 variables in children with SLI and 2 control groups
      considering predictions from 2 different theoretical perspectives,
      morphosyntactic versus morphophonological. METHOD: Children with SLI, age
      equivalent, and language-equivalent (LE) control children (n=59) completed an
      experimental sentence imitation task that generated estimates of children's
      finiteness accuracy under 2 levels of verb familiarity--familiar real verbs
      versus unfamiliar real verbs--in clausal sites marked for finiteness. Imitations
      were coded and analyzed for overall accuracy as well as finiteness marking and
      verb root imitation accuracy. RESULTS: Statistical comparisons revealed that
      children with SLI did not differ from LE children and were less accurate than age
      equivalent children on all dependent variables: overall imitation, finiteness
      marking imitation, and verb root imitation accuracy. A significant
      Group*Condition interaction for finiteness marking revealed lower levels of
      accuracy on unfamiliar verbs for the SLI and LE groups only. CONCLUSIONS:
      Findings indicate a relationship between verb familiarity and finiteness marking
      in children with SLI and younger controls and help clarify the roles of
      morphosyntax, verb lexicon, and morphophonology.

PMID- 25611350
TI  - A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems-
      insights from 3D virtual human atria and torso.
AB  - Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to
      ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin
      of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose
      the early onset of AF in a cost-effective manner. The complex and rapid atrial
      electrical activity during AF makes it difficult to obtain detailed information
      on atrial activation using the standard 12-lead ECG alone. Compared to
      conventional 12-lead ECG, more detailed ECG lead configurations may provide
      further information about spatio-temporal dynamics of the body surface potential
      (BSP) during atrial excitation. We apply a recently developed 3D human atrial
      model to simulate electrical activity during normal sinus rhythm and ectopic
      pacing. The atrial model is placed into a newly developed torso model which
      considers the presence of the lungs, liver and spinal cord. A boundary element
      method is used to compute the BSP resulting from atrial excitation. Elements of
      the torso mesh corresponding to the locations of the placement of the electrodes
      in the standard 12-lead and a more detailed 64-lead ECG configuration were
      selected. The ectopic focal activity was simulated at various origins across all
      the different regions of the atria. Simulated BSP maps during normal atrial
      excitation (i.e. sinoatrial node excitation) were compared to those observed
      experimentally (obtained from the 64-lead ECG system), showing a strong agreement
      between the evolution in time of the simulated and experimental data in the P
      wave morphology of the ECG and dipole evolution. An algorithm to obtain the
      location of the stimulus from a 64-lead ECG system was developed. The algorithm
      presented had a success rate of 93%, meaning that it correctly identified the
      origin of atrial focus in 75/80 simulations, and involved a general approach
      relevant to any multi-lead ECG system. This represents a significant improvement
      over previously developed algorithms. 

PMID- 25611352
TI  - Cervical abscess complicating an ultrasound-guided interscalene catheter.
AB  - Perineural catheters are the technique of choice for postoperative analgesia
      after painful orthopedic surgery. Infectious complications associated with
      perineural catheters, although rare, are associated with increased morbidity and
      mortality, medical cost, and hospital length of stay. In this report, we describe
      a patient in whom a cervical abscess occurred after insertion of an ultrasound
      guided interscalene catheter. 

PMID- 25611353
TI  - Editorial comment: strict asepsis-are you strictly following the directions?

PMID- 25611351
TI  - Solid-phase synthesis as a platform for the discovery of new ruthenium complexes
      for efficient release of photocaged ligands with visible light.
AB  - Ruthenium-based photocaging groups have important applications as biological
      tools and show great potential as therapeutics. A method was developed to rapidly
      synthesize, screen, and identify ruthenium-based caging groups that release
      nitriles upon irradiation with visible light. A diverse library of tetra- and
      pentadentate ligands was synthesized on polystyrene resin. Ruthenium complexes of
      the general formula [Ru(L)(MeCN)n](m+) (n = 1-3, m = 1-2) were generated from
      these ligands on solid phase and then cleaved from resin for photochemical
      analysis. Data indicate a wide range of spectral tuning and reactivity with
      visible light. Three complexes that showed strong absorbance in the visible range
      were synthesized by solution phase for comparison. Photochemical behavior of
      solution- and solid-phase complexes was in good agreement, confirming that the
      library approach is useful in identifying candidates with desired photoreactivity
      in short order, avoiding time-consuming chromatography and compound purification.

PMID- 25611354
TI  - Posttraumatic stress disorder: a special case of emergence delirium and
      anesthetic alternatives.
AB  - Two anesthesia cases are presented involving patients with a history of
      posttraumatic stress disorder (PTSD). The first patient experienced a prolonged
      dangerous flashback during emergence. In the second patient, after a thorough
      review of PTSD and the anesthesia literature, emergence was uneventful. A history
      of PTSD should be considered a risk factor in the assessment of every patient and
      anesthetic management designed to best avoid serious and potentially harmful
      reactions. 

PMID- 25611355
TI  - A patient with surgically unrepaired single ventricle and uncontrolled amiodarone
      induced thyrotoxicosis for emergent thyroidectomy.
AB  - We present the case of a 20-year-old woman with a history of hypoplastic left
      heart syndrome, D-transposition of the great arteries, and mitral/pulmonary valve
      atresia without surgical palliation, who was admitted with persistent atrial
      flutter/fibrillation and worsening cardiac function from amiodarone-induced
      thyrotoxicosis. Despite maximal medical therapy, she continued to have
      uncontrolled thyrotoxicosis and underwent successful emergent thyroidectomy under
      general anesthesia. With advances in the treatment of congenital heart disease,
      more patients are surviving to adulthood and require emergent noncardiac surgery.
      Therefore, anesthesiologists must understand the principles for managing patients
      with congenital heart disease and how the patient's physiology may affect the
      anesthetic plan. 

PMID- 25611356
TI  - Acute respiratory failure secondary to esophageal dilation from undiagnosed
      achalasia.
AB  - Achalasia is an idiopathic motility disorder causing progressive dysphagia and
      dilation of the esophagus. Rarely this esophageal dilation can cause acute
      respiratory insufficiency and/or failure. We describe a 63-year-old woman
      presenting for total knee arthroplasty in whom induction of anesthesia was
      complicated by pulmonary aspiration requiring postoperative ventilation,
      hypotension requiring vasopressor therapy, and postextubation, recurrent, acute
      respiratory failure. Computed tomography of the chest performed for suspected
      pneumothorax revealed severe esophageal dilation with a mass effect. As this case
      describes, achalasia may present with the life-threatening complication of
      respiratory failure and requires a high index of suspicion for timely diagnosis
      and appropriate interventions. 

PMID- 25611358
TI  - meso-meso linked porphyrin-[26]hexaphyrin-porphyrin hybrid arrays and their
      triply linked tapes exhibiting strong absorption bands in the NIR region.
AB  - We describe the synthesis and characterization of directly meso-meso linked
      porphyrin-[26]hexaphyrin-porphyrin hybrid oligomers and their triply linked
      (completely fused) hybrid tapes. meso-meso Linked Ni(II) porphyrin-[26]hexaphyrin
      Ni(II) porphyrin trimers were prepared by methanesulfonic acid-catalyzed cross
      condensation of meso-formyl Ni(II) porphyrins with a 5,10-diaryltripyrrane
      followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The
      Ni(II) porphyrin moieties were converted to Zn(II) porphyrins via an indirect
      route involving reduction of the [26]hexaphyrin to its 28pi congener, acid
      induced denickelation, oxidation of the [28]hexaphyrin, and finally Zn(II) ion
      insertion. Over the course of these transformations, porphyrin-[28]hexaphyrin
      porphyrin trimers have been revealed to take on a Mobius aromatic twisted
      structure for the [28]hexaphyrin segment. Oxidation of meso-meso linked hybrid
      trimer bearing 5,15-diaryl Zn(II) porphyrins with DDQ/Sc(OTf)3 under mild
      conditions resulted in meso-meso coupling oligomerization, affording the
      corresponding dimeric (hexamer), trimeric (nonamer), and tetrameric (dodecamer)
      oligomers. On the other hand, oxidation of a meso-meso linked hybrid trimer
      bearing 5,10,15-triaryl Zn(II) porphyrin terminals with DDQ/Sc(OTf)3 under
      harsher conditions afforded a meso-meso, beta-beta, beta-beta triply linked
      hybrid porphyrin tape, which displays a sharp and intense absorption band at 1912
      nm. Comparison of this extremely red-shifted absorption band with those of Zn(II)
      porphyrin tapes suggests that the bathochromic-shifting capability of a
      [26]hexaphyrin unit is large, almost equivalent to that of four individual Zn(II)
      porphyrin units. As demonstrated, the fusion of porphyrins to [26]hexaphyrin
      offers an efficient means to expand their conjugation networks, significantly
      expanding the capabilities attainable for these chromophores. 

PMID- 25611357
TI  - DNA-assembled nanoparticle rings exhibit electric and magnetic resonances at
      visible frequencies.
AB  - Metallic nanostructures can be used to manipulate light on the subwavelength
      scale to create tailored optical material properties. Next to electric responses,
      artificial optical magnetism is of particular interest but difficult to achieve
      at visible wavelengths. DNA-self-assembly has proved to serve as a viable method
      to template plasmonic materials with nanometer precision and to produce large
      quantities of metallic objects with high yields. We present here the fabrication
      of self-assembled ring-shaped plasmonic metamolecules that are composed of four
      to eight single metal nanoparticles with full stoichiometric and geometric
      control. Scattering spectra of single rings as well as absorption spectra of
      solutions containing the metamolecules are used to examine the unique plasmonic
      features, which are compared to computational simulations. We demonstrate that
      the electric and magnetic plasmon resonance modes strongly correlate with the
      exact shape of the structures. In particular, our computations reveal the
      magnetic plasmons only for particle rings of broken symmetries, which is
      consistent with our experimental data. We stress the feasibility of DNA self
      assembly as a method to create bulk plasmonic materials and metamolecules that
      may be applied as building blocks in plasmonic devices. 

PMID- 25611359
TI  - Role of the Egami Score in Predicting Intravenous Immunoglobulin Resistance in
      Kawasaki Disease Among Different Ethnicities.
AB  - Early treatment with intravenous immunoglobulin (IVIG) is necessary to help
      reduce the risk of coronary artery abnormalities, such as coronary artery
      aneurysms and to help alleviate symptoms, in Kawasaki disease. Some patients,
      however, do not respond to an initial dose of IVIG and require additional doses.
      Prediction of these IVIG nonresponders may be of assistance in altering initial
      therapy to make it more effective. The Egami score has been validated in the
      Japanese population to predict IVIG nonresponders but has shown to be ineffective
      in US populations. This study evaluates the Egami score in a Midwest US
      population, subdividing patients by race and the diagnosis of typical or atypical
      type of Kawasaki disease. Patients were included in the study if they met
      criteria for Kawasaki disease and received IVIG in the inpatient setting. A total
      of 182 patients were studied, and in all studied groups, the Egami score had poor
      sensitivity at predicting IVIG nonresponders. Sensitivity of the score differed
      between races and differed between typical and atypical Kawasaki disease. The
      Egami score, as well as other systems, have been validated to predict IVIG
      nonresponders. These, however, lack sensitivity in the US population. Other
      scores developed in the United States have also lacked sensitivity, likely due to
      the absence of race or Kawasaki disease classification as variables. The
      development of a sensitive scoring system to predict IVIG nonresponders in US
      populations will require the incorporation of race and Kawasaki disease
      classification, factors that seem to alter IVIG response.

PMID- 25611360
TI  - Raw Water Consumption Does Not Affect All-Cause or Cardiovascular Mortality: A
      Secondary Analysis.
AB  - Previous studies have examined water quality and its association with all-cause
      and cardiovascular mortality. However, there is a lack of data regarding
      association between the amount of water consumption and risk of mortality. We
      used the third National Health and Nutrition Examination Survey (NHANES III)
      database and its subsequent follow-up data. Only patients older than 45 years who
      reported amount of average water consumption and for whom follow-up mortality
      data were available were included in the study. Patients were stratified into
      following groups of average daily raw water consumption: (1) no water
      consumption, (2) <=2 cups, (3) >2 to <= 4 cups, (4) >4 to <=6 cups, (5) >6 to <=8
      cups, and (6) >=8 cups. End points studied were all-cause mortality, ischemia
      related mortality, congestive heart failure-related mortality, and stroke-related
      mortality. Baseline characteristics were compared using t tests and Mann-Whitney
      U tests. Odds ratios, 95% confidence intervals, and P values were calculated for
      univariate analysis using >6 cups to <=8 cups of water a day group as reference.
      Multivariate analysis was then performed adjusting for various factors. P values
      of less than 0.05 were considered statistically significant. A total of 7666
      patients were ultimately included in the study. Multivariate analysis
      demonstrated no significant differences in all-cause, ischemia-related, heart
      failure-related, or stroke-related mortality among various raw water intake
      groups when compared with the reference group. The significance noted for all
      cause mortality in >2 glasses to <=4 glasses a day group in the univariate
      analysis was not seen with multivariate analysis (odds ratio: 0.747; 95%
      confidence interval: 0.437-1.276; P = 0.285). Daily raw water consumption does
      not seem to impact all-cause mortality or cause-specific cardiovascular
      mortality.

PMID- 25611361
TI  - Use of noninvasive ventilation in adult patients with acute asthma exacerbation.
AB  - Noninvasive ventilation (NIV) has been found to be beneficial for respiratory
      failure in many disease states; however, limited data are available supporting
      its use in acute asthma exacerbation. A retrospective chart analysis of adult
      patients admitted for acute asthma exacerbation and treated with NIV between
      January 2007 and December 2009 at a tertiary care community hospital was done.
      Ninety-eight patient encounters were identified. Mean age of the patients was
      48.3 years, and 46% were male. Nineteen patients failed NIV and required invasive
      ventilation. There was no significant difference in the mean age, sex, race, and
      initial blood gas between patients with successful versus failed NIV. Usage of
      drugs, smoking, and history of past hospital or intensive care unit admission or
      intubation did not significantly influence the rate of failure of NIV. Patients
      who needed higher initial FiO2 were more likely to get intubated during their
      hospital stay (46.2 vs. 20.4%, P = 0.019). Patients who failed NIV were found to
      have longer duration of hospital stay (6.8 vs. 3.9 days, P= 0.016) and longer
      intensive care unit stay (4 vs. 0.9 days, P = 0.002). Use of inhalers and other
      medications was not found to significantly influence the rate of failure of NIV.
      NIV can be used initially in patients with acute asthma exacerbation, as it is
      associated with shorter duration of hospital stay and can prevent the morbidity
      of mechanical intubation. Patients with initial requirement of higher FiO2 were
      more likely to fail NIV and should be carefully monitored. 

PMID- 25611362
TI  - Association Between Opioid Abuse/Dependence and Outcomes in Hospitalized Heart
      Failure Patients.
AB  - Opioid use is associated with unintentional and intentional overdose and is one
      of the leading causes of emergency room visits and accidental deaths. However,
      the association between opioid abuse/dependence and outcomes in hospitalized
      patients has not been well studied. Congestive heart failure (HF) is the fourth
      most common cause of hospitalization in the United States. The purpose of this
      study was to examine the effect of opioid abuse/dependence on outcomes in
      patients hospitalized with HF. We queried the 2002-2010 Nationwide Inpatient
      Sample databases to identify all patients aged 18 years and older admitted with
      the primary diagnosis of HF. Multivariate logistic regression analysis was used
      to compare the frequency of hospital-acquired conditions (HACs) and in-hospital
      mortality between patients with and without a history of opioid abuse/dependence.
      Of 9,993,240 patients with HF, 29,014 had a history of opioid abuse or
      dependence. Opioid abusers/dependents were likely to be younger men of poor
      socioeconomic background with self pay or Medicaid as their primary payer. They
      had a lower prevalence of dyslipidemia, diabetes mellitus, coronary artery
      disease, prior myocardial infarction, and peripheral vascular disease (P < 0.001
      for all). They were more likely to be smokers and have chronic pulmonary disease,
      depression, liver disease, and obesity (P < 0.001 for all). Patients with a
      history of opioid abuse/dependence had lower incidence of HACs (14.8% vs. 16.5%,
      adjusted odds ratio: 0.71, P < 0.001) and lower in-hospital mortality (1.3% vs.
      3.6%, adjusted odds ratio: 0.64, P < 0.001) as compared with patients without
      prior opioid abuse/dependence. In conclusion, among adult patients aged 18 years
      and older hospitalized with HF, opioid abuse/dependence was associated with lower
      frequency of HACs and lower in-hospital mortality. 

PMID- 25611363
TI  - A Call of Alert for the Ambu AuraStraight Disposable Laryngeal Mask.
AB  - One day after removal of an AuraStraight disposable laryngeal mask, a plastic
      laryngeal mask airway cuff shield was retrieved from the oropharynx of a 5-year
      old child refusing to eat, drooling, and pointing to her throat. We discuss the
      reasons why this occurred and suggest how it can be prevented in the future. 

PMID- 25611364
TI  - Caring for a patient with unexpected pheochromocytoma complicated by medical
      fraud.
AB  - We report a case of a patient who used multiple aliases as part of a medical
      fraud scheme. As a consequence, the surgical team was unaware of a left-sided
      adrenal mass that had been documented for this patient under another name. In the
      operating room, severe hypertension from the undiagnosed pheochromocytoma led to
      a ventricular fibrillation cardiac arrest. This case demonstrates the importance
      of physician awareness of medical identity fraud and its potential consequences. 

PMID- 25611365
TI  - A novel case of adult, acute epiglottitis successfully treated with noninvasive
      ventilation.
AB  - Acute adult epiglottitis is a rare and potentially fatal upper airway condition,
      requiring prompt recognition, resuscitation, stabilization, and transfer to
      definitive care. Treatment centers on skilled airway management and early
      antimicrobial therapy. We describe a patient with acute adult epiglottitis in
      whom airway management using noninvasive positive pressure ventilation was
      successful allowing avoidance of tracheal intubation. 

PMID- 25611366
TI  - In-plane ultrasound imaging of the vertebral artery for safe pediatric internal
      jugular vein cannulation.
AB  - Before cannulation of the internal jugular vein (IJV) in 4 pediatric patients, we
      obtained in-plane and out-of-plane ultrasound images of the vertebral artery
      (VA). In 2 of 4 patients, abnormalities were identified and best imaged in the in
      plane view. In one patient, the right VA had an anomalous origin and course
      behind the IJV. In another patient, the in-plane image of both the IJV and the VA
      clearly showed a narrowed IJV. In some cases, the relationship between the VA and
      IJV may be more clearly understood with in-plane imaging. 

PMID- 25611367
TI  - Functionalization of quantum rods with oligonucleotides for programmable assembly
      with DNA origami.
AB  - The DNA-mediated self-assembly of CdSe/CdS quantum rods (QRs) onto DNA origami is
      described. Two QR types with unique optical emission and high polarization were
      synthesized, and then functionalized with oligonucleotides (ssDNA) using a novel
      protection-deprotection approach, which harnessed ssDNA's tailorable rigidity and
      denaturation temperature to increase DNA coverage by reducing non-specific
      coordination and wrapping. The QR assembly was programmable, and occurred at two
      different assembly zones that had capture strands in parallel alignment. QRs with
      different optical properties were assembled, opening up future studies on
      orientation dependent QR FRET. The QR-origami conjugates could be purified via
      gel electrophoresis and sucrose gradient ultracentrifugation. Assembly yields, QR
      stoichiometry and orientation, as well as energy transfer implications were
      studied in light of QR distances, origami flexibility, and conditions. 

PMID- 25611368
TI  - Palladium-catalyzed intramolecular C(sp(2))-H imidoylation for the synthesis of
      six-membered N-heterocycles.
AB  - A new strategy for the construction of phenanthridine and isoquinoline scaffolds,
      starting from arenes containing a pending isocyanide moiety under palladium
      catalysis, has been developed. This process involves sequential intermolecular
      isocyanide insertion to an aryl palladium(II) intermediate and intramolecular
      aromatic C-H activation as key steps. Alkyl palladium(II) intermediate lacking
      beta-hydrogen is also applicable to this reaction, generating unique
      bisheterocyclic scaffolds with three C-C bonds being formed consecutively. 

PMID- 25611369
TI  - Correlation of the physicochemical properties of natural organic matter samples
      from different sources to their effects on gold nanoparticle aggregation in
      monovalent electrolyte.
AB  - Engineered nanoparticles (NPs) released into natural environments will interact
      with natural organic matter (NOM) or humic substances, which will change their
      fate and transport behavior. Quantitative predictions of the effects of NOM are
      difficult because of its heterogeneity and variability. Here, the effects of six
      types of NOM and molecular weight fractions of each on the aggregation of citrate
      stabilized gold NPs are investigated. Correlations of NP aggregation rates with
      electrophoretic mobility and the molecular weight distribution and chemical
      attributes of NOM (including UV absorptivity or aromaticity, functional group
      content, and fluorescence) are assessed. In general, the >100 kg/mol components
      provide better stability than lower molecular weight components for each type of
      NOM, and they contribute to the stabilizing effect of the unfractionated NOM even
      in small proportions. In many cases, unfractionated NOM provided better stability
      than its separated components, indicating a synergistic effect between the high
      and low molecular weight fractions for NP stabilization. Weight-averaged
      molecular weight was the best single explanatory variable for NP aggregation
      rates across all NOM types and molecular weight fractions. NP aggregation showed
      poorer correlation with UV absorptivity, but the exponential slope of the UV-vis
      absorbance spectrum was a better surrogate for molecular weight. Functional group
      data (including reduced sulfur and total nitrogen content) were explored as
      possible secondary parameters to explain the strong stabilizing effect of a low
      molecular weight Pony Lake fulvic acid sample to the gold NPs. These results can
      inform future correlations and measurement requirements to predict NP attachment
      in the presence of NOM. 

PMID- 25611370
TI  - Measurement of internal substrate binding in dehaloperoxidase-hemoglobin by
      competition with the heme-fluoride binding equilibrium.
AB  - The application of fluoride anion as a probe for investigating the internal
      substrate binding has been developed and applied to dehaloperoxidase-hemoglobin
      (DHP) from Amphitrite ornata. By applying the fluoride titration strategy using
      UV-vis spectroscopy, we have studied series of halogenated phenols, other
      substituted phenols, halogenated indoles, and several natural amino acids that
      bind internally (and noncovalently) in the distal binding pocket of the heme.
      This approach has identified 2,4-dibromophenol (2,4-DBP) as the tightest binding
      substrate discovered thus far, with approximately 20-fold tighter binding
      affinity than that of 4-bromophenol (4-BP), a known internally binding inhibitor
      in DHP. Combined with resonance Raman spectroscopy, we have confirmed that
      competitive binding equilibria exist between fluoride anion and internally bound
      molecules. We have further investigated the hydrogen bonding network of the
      active site of DHP that stabilizes the exogenous fluoride ligand. These
      measurements demonstrate a general method for determination of differences in
      substrate binding affinity based on detection of a competitive fluoride binding
      equilibrium. The significance of the binding that 2,4-dibromophenol binds more
      tightly than any other substrate is evident when the structural and mechanistic
      data are taken into consideration. 

PMID- 25611371
TI  - Graphene oxide-promoted reshaping and coarsening of gold nanorods and
      nanoparticles.
AB  - This paper describes thermally induced reshaping and coarsening behaviors of gold
      nanorods and nanoparticles immobilized on the surface of graphene oxide.
      Cetyltrimethylammonium bromide-stabilized gold nanorods with an aspect ratio of
      ~3.5 (54:15 nm) and glutathione-capped gold nanoparticles with an average core
      size of ~3 nm were synthesized and self-assembled onto the surface of graphene
      oxide. The hybrid materials were then heated at different temperatures ranging
      from 50 to 300  degrees C. The effects of heat treatments were monitored using UV
      vis spectroscopy and transmission electron microscopy (TEM). These results were
      directly compared with those of heat-treated free-standing gold nanorods and
      nanoparticles without graphene oxide to understand the heat-induced morphological
      changes of the nanohybrids. The obtained results showed that the gold nanorods
      would undergo a complete reshaping to spherical particles at the temperature of
      50  degrees C when they are assembled on graphene oxide. In comparison, the
      complete reshaping of free-standing gold nanorods to spherical particles would
      ultimately require a heating of the samples at 200  degrees C. In addition, the
      spherical gold nanoparticles immobilized on graphene oxide would undergo a rapid
      coarsening at the temperature of 100-150  degrees C, which was lower than the
      temperature (150-200  degrees C) required for visible coarsening of free-standing
      gold nanoparticles. The results indicated that graphene oxide facilitates the
      reshaping and coarsening of gold nanorods and nanoparticles, respectively, during
      the heat treatments. The stripping and spillover of stabilizing ligands promoted
      by graphene oxide are proposed to be the main mechanism for the enhancements in
      the heat-induced transformations of nanohybrids. 

PMID- 25611372
TI  - Synthesis of scaly Sn3O4/TiO2 nanobelt heterostructures for enhanced UV-visible
      light photocatalytic activity.
AB  - A novel scaly Sn3O4/TiO2 nanobelt heterostructured photocatalyst was fabricated
      via a facile hydrothermal route. The scaly Sn3O4 nanoflakes can be synthesized in
      situ and assembled on surface coarsened TiO2 nanobelts through a hydrothermal
      process. The morphology and distribution of Sn3O4 nanoflakes can be well
      controlled by simply tuning the Sn/Ti molar ratio of the reactants. Compared with
      single phase nanostructures of Sn3O4 and TiO2, the scaly hybrid nanobelts
      exhibited markedly enhanced photoelectrochemical (PEC) response, which caused
      higher photocatalytic hydrogen evolution even without the assistance of Pt as a
      co-catalyst, and enhanced the degradation ability of organic pollutants under
      both UV and visible light irradiation. In addition to the increased exposure of
      active facets and broad light absorption, the outstanding performance is ascribed
      to the matching energy band structure between Sn3O4 and TiO2 at the two sides of
      the heterostructure, which efficiently reduces the recombination of photo-excited
      electron-hole pairs and prolongs the lifetime of charge carriers. Both
      photocatalytic assessment and PEC tests revealed that Sn3O4/TiO2 heterostructures
      with a molar ratio of Sn/Ti of 2/1 exhibited the highest photocatalytic activity.
      This study provides a facile and low-cost method for the large scale production
      of Sn3O4 based materials in various applications. 

PMID- 25611375
TI  - Mechanism of a molecular photo-switch adsorbed on Si(100).
AB  - We present a very compact molecular photoswitch on the technologically important
      Si(100) surface. Its adsorption configuration is determined by a combined
      scanning tunneling microscopy (STM) and density functional theory (DFT) study.
      The mechanisms of the isomerization reactions are discussed in view of DFT
      calculations and proven by in situ light irradiation. 

PMID- 25611373
TI  - Cold-inducible RNA-binding protein promotes the development of liver cancer.
AB  - Most hepatocellular carcinomas (HCCs) develop in the context of chronic liver
      inflammation. Oxidative stress is thought to play a major role in the
      pathogenesis of HCC development. In this study, we examined whether cold
      inducible RNA-binding protein (Cirp) controls reactive oxygen species (ROS)
      accumulation and development of HCC by using murine models of
      hepatocarcinogenesis and human liver samples. Cirp expression, ROS accumulation,
      and CD133 expression were increased in the liver of tumor-harboring mice. Cirp
      deficiency reduced production of interleukin-1beta and interleukin-6 in Kupffer
      cells, ROS accumulation, and CD133 expression, leading to attenuated
      hepatocarcinogenesis. Thioacetamide treatment enhanced hepatic expression of
      CD133 and phosphorylated signal transducer and activator of transcription 3
      (STAT3), which was prevented by treatment with the antioxidant butylated
      hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively
      correlated with Cirp expression in liver. Cirp appears to play a critical
      carcinogenic function and its expression might be a useful biomarker for HCC risk
      prediction. 

PMID- 25611374
TI  - GADA and anti-ZnT8 complicate the outcome of phenotypic type 2 diabetes of
      adults.
AB  - BACKGROUND: A proportion of phenotypic type 2 diabetes (T2D) patients produce
      pancreatic autoantibodies and a majority of T2D patients develop serious life
      disabling complications over time despite the implementation of adequate clinical
      interventions. This study determined whether the presence of pancreatic
      autoantibodies (GADA, IA-2A, anti-ZnT8, or ICA) was associated with serious
      complications or concomitant diseases of adult patients diagnosed with T2D (N =
      305). MAIN RESULTS: In the study population, 22.3% (N = 68) of subjects were
      positive for at least 1 of the 4 of the markers associated with autoimmune
      diabetes (presence of pancreatic autoantibody - pAb), followed by GADA (14.1%, N
      = 43), ICA (8.9%, N = 27), anti-ZnT8 (5.6%, N = 17) and IA-2A (2.0%, N = 6).
      Logistic regression analysis adjusted for patient's age, gender and duration of
      T2D revealed that (i) pAb was associated with higher prevalence of adiposity
      (odds ratio of adjusted regression model (adOR) 2.51, P = 0.032); (ii) pAb, GADA
      and anti-ZnT8 were associated with autoimmune thyroid disease (adORs 3.07, P =
      0.012; 6.29, P < 0.001 and 3.52, P = 0.052, respectively); (iii) pAb and GADA, in
      particular, were risk factors for neurological complications (adORs 2.10, P =
      0.036; 2.76, P = 0.009, respectively) and polyneuropathy in particular (adORs
      2.60, P = 0.012; 3.10, P = 0.007, respectively); and (iv) anti-ZnT8 was a risk
      factor for developing nephropathy (adOR 4.61, P = 0.022). In addition, adiposity
      was associated with 5.3-year earlier onset of disease (adjusted linear regression
      model, P = 0.006). CONCLUSIONS: These results suggest that GADA and anti-ZnT8 are
      associated with progression of serious T2D complications, including
      polyneuropathy and nephropathy. In addition, adiposity represents a significant
      risk for autoimmunity development in T2D patients.

PMID- 25611376
TI  - Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice.
AB  - Ageing is a complex biological process for which underlying biochemical changes
      are still largely unknown. We performed comparative profiling of the cellular
      proteome and metabolome to understand the molecular basis of ageing in Caspase-2
      deficient (Casp2(-/-)) mice that are a model of premature ageing in the absence
      of overt disease. Age-related changes were determined in the liver and serum of
      young (6-9 week) and aged (18-24 month) wild-type and Casp2(-/-) mice. We
      identified perturbed metabolic pathways, decreased levels of ribosomal and
      respiratory complex proteins and altered mitochondrial function that contribute
      to premature ageing in the Casp2(-/-) mice. We show that the metabolic profile
      changes in the young Casp2(-/-) mice resemble those found in aged wild-type mice.
      Intriguingly, aged Casp2(-/-) mice were found to have reduced blood glucose and
      improved glucose tolerance. These results demonstrate an important role for
      caspase-2 in regulating proteome and metabolome remodelling during ageing. 

PMID- 25611377
TI  - DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.
AB  - Despite recent progress in the identification of genetic and molecular
      alternations in colorectal carcinoma, the precise molecular pathogenesis remains
      unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family,
      pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization
      domain-like receptor family of proteins that are key organization proteins in the
      inflammasome. It is reported that NALP1 plays a central role in cell apoptosis,
      pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2
      deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic
      disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined
      the expression of NALP1 in human normal and cancerous colon tissues using tissue
      microarray, western blot and quantitative real-time PCR and we measured the
      expression of NALP1 in three kinds of colon cancer cell lines and animal models
      before and after treatment with DAC. Furthermore, we examined the treatment
      effects of DAC on colon cancer in our animal model. Our data indicate that NALP1
      is expressed low in human colorectal tumoral tissues relative to paratumoral
      tissues and was associated with the survival and tumor metastasis of patients.
      The expression of NALP1 increased after treatment with DAC both in vitro and in
      vivo. Furthermore, DAC suppressed the growth of colon cancer and increased
      lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in
      colon cancer and associated with the survival and tumor metastasis of patients,
      and treatment with DAC can restore NALP1 levels to suppress the growth of colon
      cancer. 

PMID- 25611379
TI  - Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in
      human osteosarcoma cells: an in vitro and in vivo study.
AB  - Osteosarcoma is the most common primary malignant tumor of bone, the long-term
      survival of which has stagnated in the past several decades. Celastrol, a
      triterpene from traditional Chinese medicine, has been proved to possess potent
      anti-tumor effect on various cancers. However, the effect of celastrol on human
      osteosarcoma and the underlying mechanisms remains to be elucidated. We reported
      here that celastrol could inhibit cell proliferation by causing G2/M phase
      arrest. Exposure to celastrol resulted in the activation of caspase-3, -8, and 
      9, indicating that celastrol induced apoptosis through both extrinsic and
      intrinsic pathways. Autophagy occurred in celastrol-treated cells as evidenced by
      formation of autophagosome and accumulation of LC3B-II. The celastrol-induced
      cell death was remarkably restored by the combination of autophagy and apoptosis
      inhibitors. Furthermore, inhibition of apoptosis enhanced autophagy while
      suppression of autophagy diminished apoptosis. Celastrol also induced JNK
      activation and ROS generation. The JNK inhibitor significantly attenuated
      celastrol-triggered apoptosis and autophagy while ROS scavenger could completely
      reverse them. The ROS scavenger also prevented G2/M phase arrest and
      phosphorylation of JNK. Importantly, we found that celastrol had the similar
      effects on primary osteosarcoma cells. Finally, in vivo, celastrol suppressed
      tumor growth in the mouse xenograft model. Taken together, our results revealed
      that celastrol caused G2/M phase arrest, induced apoptosis and autophagy via the
      ROS/JNK signaling pathway in human osteosarcoma cells. Celastrol is therefore a
      promising candidate for development of antitumor drugs targeting osteosarcoma. 

PMID- 25611378
TI  - The malignant phenotype in breast cancer is driven by eIF4A1-mediated changes in
      the translational landscape.
AB  - Human mRNA DeXD/H-box helicases are ubiquitous molecular motors that are required
      for the majority of cellular processes that involve RNA metabolism. One of the
      most abundant is eIF4A, which is required during the initiation phase of protein
      synthesis to unwind regions of highly structured mRNA that would otherwise impede
      the scanning ribosome. Dysregulation of protein synthesis is associated with
      tumorigenesis, but little is known about the detailed relationships between RNA
      helicase function and the malignant phenotype in solid malignancies. Therefore,
      immunohistochemical analysis was performed on over 3000 breast tumors to
      investigate the relationship among expression of eIF4A1, the helicase-modulating
      proteins eIF4B, eIF4E and PDCD4, and clinical outcome. We found eIF4A1, eIF4B and
      eIF4E to be independent predictors of poor outcome in ER-negative disease, while
      in contrast, the eIF4A1 inhibitor PDCD4 was related to improved outcome in ER
      positive breast cancer. Consistent with these data, modulation of eIF4A1, eIF4B
      and PCDC4 expression in cultured MCF7 cells all restricted breast cancer cell
      growth and cycling. The eIF4A1-dependent translatome of MCF7 cells was defined by
      polysome profiling, and was shown to be highly enriched for several classes of
      oncogenic genes, including G-protein constituents, cyclins and protein kinases,
      and for mRNAs with G/C-rich 5'UTRs with potential to form G-quadruplexes and with
      3'UTRs containing microRNA target sites. Overall, our data show that
      dysregulation of mRNA unwinding contributes to the malignant phenotype in breast
      cancer via preferential translation of a class of genes involved in pro-oncogenic
      signaling at numerous levels. Furthermore, immunohistochemical tests are
      promising biomarkers for tumors sensitive to anti-helicase therapies. 

PMID- 25611380
TI  - Bmi1 regulates auditory hair cell survival by maintaining redox balance.
AB  - Reactive oxygen species (ROS) accumulation are involved in noise- and ototoxic
      drug-induced hair cell loss, which is the major cause of hearing loss. Bmi1 is a
      member of the Polycomb protein family and has been reported to regulate
      mitochondrial function and ROS level in thymocytes and neurons. In this study, we
      reported the expression of Bmi1 in mouse cochlea and investigated the role of
      Bmi1 in hair cell survival. Bmi1 expressed in hair cells and supporting cells in
      mouse cochlea. Bmi1(-/-) mice displayed severe hearing loss and patched outer
      hair cell loss from postnatal day 22. Ototoxic drug-induced hair cells loss
      dramatically increased in Bmi1(-/-) mice compared with that in wild-type controls
      both in vivo and in vitro, indicating Bmi1(-/-) hair cells were significantly
      more sensitive to ototoxic drug-induced damage. Cleaved caspase-3 and TUNEL
      staining demonstrated that apoptosis was involved in the increased hair cell loss
      of Bmi1(-/-) mice. Aminophenyl fluorescein and MitoSOX Red staining showed the
      level of free radicals and mitochondrial ROS increased in Bmi1(-/-) hair cells
      due to the aggravated disequilibrium of antioxidant-prooxidant balance.
      Furthermore, the antioxidant N-acetylcysteine rescued Bmi1(-/-) hair cells from
      neomycin injury both in vitro and in vivo, suggesting that ROS accumulation was
      mainly responsible for the increased aminoglycosides sensitivity in Bmi1(-/-)
      hair cells. Our findings demonstrate that Bmi1 has an important role in hair cell
      survival by controlling redox balance and ROS level, thus suggesting that Bmi1
      may work as a new therapeutic target for the prevention of hair cell death. 

PMID- 25611381
TI  - Intracellular annexin A2 regulates NF-kappaB signaling by binding to the p50
      subunit: implications for gemcitabine resistance in pancreatic cancer.
AB  - Annexin A2 (ANXA2) expression is highly upregulated in many types of cancer.
      Although cell surface localization of ANXA2 has been reported to have a critical
      role in the progression and metastasis of a variety of tumors, including
      pancreatic cancer, the biological role of intracellular ANXA2 is not fully
      understood. Herein the role of intracellular ANXA2 was investigated in a
      pancreatic cancer cell line. We first determined whether ANXA2 is involved in NF
      kappaB signaling pathways. ANXA2 bound to the p50 subunit of NF-kappaB in a
      calcium-independent manner, and the ANXA2-p50 complex translocated into the
      nucleus. Furthermore, ANXA2 increased the transcriptional activity of NF-kappaB
      in both the resting and activated states and upregulated the transcription of
      several target genes downstream of NF-kappaB, including that encoding interleukin
      (IL)-6, which contributes to anti-apoptotic signaling. In Mia-Paca2 cells, we
      determined the effects of wild-type ANXA2 and an ANXA2 mutant, Y23A, which
      suppresses the cell surface localization, on upregulation of NF-kappaB
      transcriptional activity and secretion of IL-6. Both wild-type and Y23A ANXA2
      induced anti-apoptotic effects in response to treatment with tumor necrosis
      factor-alpha or gemcitabine. Based on these results, we suggest that ANXA2
      mediates resistance to gemcitabine by directly increasing the activity of NF
      kappaB. Collectively, these data may provide additional information about the
      biological role of ANXA2 in pancreatic cancer and suggest that ANXA2 is a
      potential biomarker for the drug resistance phenotype and a candidate therapeutic
      target for the treatment of pancreatic cancer. 

PMID- 25611382
TI  - BMCC1, which is an interacting partner of BCL2, attenuates AKT activity,
      accompanied by apoptosis.
AB  - BNIP2 and Cdc42GAP homology (BCH) motif-containing molecule at the carboxyl
      terminal region 1 (BMCC1) gene is highly expressed in patients with favorable
      neuroblastoma (NB). It encodes a 340-kDa protein with a conserved BCH scaffold
      domain that may regulate signaling networks and multiple cellular functions,
      including apoptosis. In this study, we determined the mechanism by which BMCC1
      promotes apoptosis in human NB and non-NB cells, as BMCC1 is normally expressed
      in various organs, particularly in neuronal and epithelial tissues. We
      demonstrated in this report that BMCC1 was induced by DNA damage, one of the
      triggers of intrinsic apoptosis. Accordingly, we investigated whether BMCC1
      expression impacts intracellular signals in the regulation of apoptosis via its C
      terminal region containing BCH scaffold domain. BMCC1 decreased phosphorylation
      of survival signals on AKT and its upstream kinase PDK1. BMCC1 upregulation was
      correlated with the activation of forkhead box-O3a (FOXO3a) (a downstream inducer
      of apoptosis, which is suppressed by AKT) and induction of BCL2 inhibitor BIM,
      suggesting that BMCC1 negatively regulates phosphorylation pathway of AKT,
      resulted in apoptosis. In addition, we found that BNIP2 homology region of BMCC1
      interacts with BCL2. Intrinsic apoptosis induced by DNA damage was enhanced by
      BMCC1 overexpression, and was diminished by knockdown of BMCC1. Taken together,
      we conclude that BMCC1 promotes apoptosis at multiple steps in AKT-mediated
      survival signal pathway. These steps include physical interaction with BCL2 and
      attenuation of AKT-dependent inhibition of FOXO3a functions, such as
      transcriptional induction of BIM and phosphorylation of ataxia telangiectasia
      mutated (ATM) after DNA damage. We propose that downregulation of BMCC1
      expression, which is frequently observed in unfavorable NB and epithelial-derived
      cancers, may facilitate tumor development by abrogating DNA damage repair and
      apoptosis. 

PMID- 25611383
TI  - NF-kappaB-dependent and -independent epigenetic modulation using the novel anti
      cancer agent DMAPT.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) is constitutively
      active in several cancers and is a target of therapeutic development. We recently
      developed dimethylaminoparthenolide (DMAPT), a clinical grade water-soluble
      analog of parthenolide, as a potent inhibitor of NF-kappaB and demonstrated in
      vitro and in vivo anti-tumor activities in multiple cancers. In this study, we
      show DMAPT is an epigenetic modulator functioning in an NF-kappaB-dependent and 
      independent manner. DMAPT-mediated NF-kappaB inhibition resulted in elevated
      histone H3K36 trimethylation (H3K36me3), which could be recapitulated through
      genetic ablation of the p65 subunit of NF-kappaB or inhibitor-of-kappaB alpha
      super-repressor overexpression. DMAPT treatment and p65 ablation increased the
      levels of H3K36 trimethylases NSD1 (KMT3B) and SETD2 (KMT3A), suggesting that NF
      kappaB directly represses their expression and that lower H3K36me3 is an
      epigenetic marker of constitutive NF-kappaB activity. Overexpression of a
      constitutively active p65 subunit of NF-kappaB reduced NSD1 and H3K36me3 levels.
      NSD1 is essential for DMAPT-induced expression of pro-apoptotic BIM, indicating a
      functional link between epigenetic modification and gene expression.
      Interestingly, we observed enhanced H4K20 trimethylation and induction of H4K20
      trimethylase KMT5C in DMAPT-treated cells independent of NF-kappaB inhibition.
      These results add KMT5C to the list NF-kappaB-independent epigenetic targets of
      parthenolide, which include previously described histone deacetylase 1 (HDAC-1)
      and DNA methyltransferase 1. As NSD1 and SETD2 are known tumor suppressors and
      loss of H4K20 trimethylation is an early event in cancer progression, which
      contributes to genomic instability, we propose DMAPT as a potent pharmacologic
      agent that can reverse NF-kappaB-dependent and -independent cancer-specific
      epigenetic abnormalities. 

PMID- 25611384
TI  - Die for the community: an overview of programmed cell death in bacteria.
AB  - Programmed cell death is a process known to have a crucial role in many aspects
      of eukaryotes physiology and is clearly essential to their life. As a
      consequence, the underlying molecular mechanisms have been extensively studied in
      eukaryotes and we now know that different signalling pathways leading to
      functionally and morphologically different forms of death exist in these
      organisms. Similarly, mono-cellular organism can activate signalling pathways
      leading to death of a number of cells within a colony. The reason why a single
      cell organism would activate a program leading to its death is apparently
      counterintuitive and probably for this reason cell death in prokaryotes has
      received a lot less attention in the past years. However, as summarized in this
      review there are many reasons leading to prokaryotic cell death, for the benefit
      of the colony. Indeed, single-celled organism can greatly benefit from
      multicellular organization. Within this forms of organization, regulation of
      death becomes an important issue, contributing to important processes such as:
      stress response, development, genetic transformation, and biofilm formation. 

PMID- 25611386
TI  - The BH3-only protein Bad is dispensable for TNF-mediated cell death.
AB  - Tumor necrosis factor (TNF) is a key signaling molecule orchestrating immune and
      inflammatory responses and possesses the capacity to trigger apoptotic as well as
      necroptotic cell death. Apoptotic cell death elicited by TNF has been
      demonstrated to engage pro-apoptotic Bcl-2 family proteins, most prominently the
      BH3-only protein Bid, a key substrate of caspase-8, the key effector protease
      downstream of TNF receptor I. Most recently, the BH3 domain-containing protein
      Bad (Bcl-2-antagonist of cell death) has been shown to be rate limiting for TNF
      mediated cell death, suggesting possible synergy with Bid, but genetic analyses
      presented here demonstrate that it is dispensable for this process. 

PMID- 25611385
TI  - A G-quadruplex DNA structure resolvase, RHAU, is essential for spermatogonia
      differentiation.
AB  - G-quadruplex (G4) DNA and G4 DNA resolvase are involved in a variety of
      biological processes. To understand the biological function of G4 DNA structures
      and their resolvases in spermatogenesis, we investigated the distribution of G4
      structures in mouse testis and identified their alterations during
      spermatogenesis. Meanwhile, we studied the function of RNA helicase associated
      with AU-rich element (RHAU), a G4 DNA resolvase, in spermatogenesis with a germ
      cell-specific knockout mouse model. The results showed that the ablation of RHAU
      in germ cells caused the increase of G4 structures and thus resulted in the
      decrease of spermatogonial differentiation. c-kit, a spermatogonia
      differentiation-related gene, contains two G4 DNA motifs on its promoter. We
      found its expression was significantly downregulated in RHAU conditional knockout
      testis. A further analysis demonstrated that RHAU directly bound to the G4
      structures to activate c-kit expression. We concluded that RHAU regulates
      spermatogonia differentiation by promoting c-kit expression via directly binding
      to the G4 DNA motifs c-kit promoter. 

PMID- 25611387
TI  - ING1b negatively regulates HIF1alpha protein levels in adipose-derived stromal
      cells by a SUMOylation-dependent mechanism.
AB  - Hypoxic niches help maintain mesenchymal stromal cell properties, and their
      amplification under hypoxia sustains their immature state. However, how MSCs
      maintain their genomic integrity in this context remains elusive, since hypoxia
      may prevent proper DNA repair by downregulating expression of BRCA1 and RAD51.
      Here, we find that the ING1b tumor suppressor accumulates in adipose-derived
      stromal cells (ADSCs) upon genotoxic stress, owing to SUMOylation on K193 that is
      mediated by the E3 small ubiquitin-like modifier (SUMO) ligase protein inhibitor
      of activated STAT protein gamma (PIAS4). We demonstrate that ING1b finely
      regulates the hypoxic response by triggering HIF1alpha proteasomal degradation.
      On the contrary, when mutated on its SUMOylation site, ING1b failed to
      efficiently decrease HIF1alpha levels. Consistently, we observed that the
      adipocyte differentiation, generally described to be downregulated by hypoxia,
      was highly dependent on ING1b expression, during the early days of this process.
      Accordingly, contrary to what was observed with HIF1alpha, the absence of ING1b
      impeded the adipogenic induction under hypoxic conditions. These data indicate
      that ING1b contributes to adipogenic induction in adipose-derived stromal cells,
      and thus hinders the phenotype maintenance of ADSCs. 

PMID- 25611388
TI  - Interaction of differentiated human adipocytes with macrophages leads to
      trogocytosis and selective IL-6 secretion.
AB  - Obesity leads to adipose tissue inflammation that is characterized by increased
      release of proinflammatory molecules and the recruitment of activated immune
      cells. Although macrophages are present in the highest number among the immune
      cells in obese adipose tissue, not much is known about their direct interaction
      with adipocytes. We have introduced an ex vivo experimental system to
      characterize the cellular interactions and the profile of secreted cytokines in
      cocultures of macrophages and human adipocytes differentiated from either
      mesenchymal stem cells or a preadipocyte cell line. As observed by time-lapse
      microscopy, flow, and laser-scanning cytometry, macrophages phagocytosed bites of
      adipocytes (trogocytosis), which led to their de novo, phagocytosis and NF-kappaB
      dependent synthesis, then release of interleukin (IL)-6 and monocyte
      chemoattractant protein (MCP)-1. IL-6 secretion was not accompanied by secretion
      of other proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and
      IL-8, except MCP-1. LPS-induced release of TNF-alpha, IL-8 and MCP-1 was
      decreased in the presence of the differentiated adipocytes but the IL-6 level did
      not subside suggesting that phagocytosis-dependent IL-6 secretion may have
      significant regulatory function in the inflamed adipose tissue. 

PMID- 25611389
TI  - Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory
      networks in colorectal cancer.
AB  - Despite recent advances in cancer management, colorectal cancer (CRC) remains the
      third most common cancer and a major health-care problem worldwide. MicroRNAs
      have recently emerged as key regulators of cancer development and progression by
      targeting multiple cancer-related genes; however, such regulatory networks are
      not well characterized in CRC. Thus, the aim of this study was to perform global
      messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples
      and adjacent normal tissues and to identify potential miRNA-mRNA regulatory
      networks. Our data revealed 1273 significantly upregulated and 1902 downregulated
      genes in CRC. Pathway analysis revealed significant enrichment in cell cycle,
      integrated cancer, Wnt (wingless-type MMTV integration site family member),
      matrix metalloproteinase, and TGF-beta pathways in CRC. Pharmacological
      inhibition of Wnt (using XAV939 or IWP-2) or TGF-beta (using SB-431542) pathways
      led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our
      data revealed up- (42) and downregulated (61) microRNAs in the same matched
      samples. Using target prediction and bioinformatics, ~77% of the upregulated
      genes were predicted to be targeted by microRNAs found to be downregulated in
      CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was
      found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal
      7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p
      (R(2)=0.56, P=0.0001) and hsa-let-7b-5p (R(2)=0.19, P=0.02) expression was
      observed in the same samples, corroborating the belief of EZH2 being a bona fide
      target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to
      significant reduction in trimethylated histone H3 on lysine 27 (H3K27)
      methylation, marked reduction in cell proliferation, and migration in vitro.
      Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar
      effects on CRC cell growth in vitro. Therefore, our data have revealed several
      hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting
      relevant networks as potential therapeutic strategy for CRC. 

PMID- 25611390
TI  - The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like
      function triggering oligomerization and crosslinking upon oxidative stress
      related to cell death.
AB  - The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in
      cellular redox systems and reductive pathways. Here we discovered that an
      evolutionarily conserved and surface-exposed tryptophan residue of the enzyme
      (Trp114) is excessively reactive to oxidation and exerts regulatory functions.
      The results indicate that it serves as an electron relay communicating with the
      FAD moiety of the enzyme, and, when oxidized, it facilitates oligomerization of
      TrxR1 into tetramers and higher multimers of dimers. A covalent link can also be
      formed between two oxidized Trp114 residues of two subunits from two separate
      TrxR1 dimers, as found both in cell extracts and in a crystal structure of
      tetrameric TrxR1. Formation of covalently linked TrxR1 subunits became
      exaggerated in cells on treatment with the pro-oxidant p53-reactivating
      anticancer compound RITA, in direct correlation with triggering of a cell death
      that could be prevented by antioxidant treatment. These results collectively
      suggest that Trp114 of TrxR1 serves a function reminiscent of an irreversible
      sensor for excessive oxidation, thereby presenting a previously unrecognized
      level of regulation of TrxR1 function in relation to cellular redox state and
      cell death induction. 

PMID- 25611391
TI  - PINK1-induced mitophagy promotes neuroprotection in Huntington's disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disorder caused by
      aberrant expansion of CAG repeat in the huntingtin gene. Mutant Huntingtin (mHtt)
      alters multiple cellular processes, leading to neuronal dysfunction and death.
      Among those alterations, impaired mitochondrial metabolism seems to have a major
      role in HD pathogenesis. In this study, we used the Drosophila model system to
      further investigate the role of mitochondrial damages in HD. We first analyzed
      the impact of mHtt on mitochondrial morphology, and surprisingly, we revealed the
      formation of abnormal ring-shaped mitochondria in photoreceptor neurons. Because
      such mitochondrial spheroids were previously detected in cells where mitophagy is
      blocked, we analyzed the effect of PTEN-induced putative kinase 1 (PINK1), which
      controls Parkin-mediated mitophagy. Consistently, we found that PINK1
      overexpression alleviated mitochondrial spheroid formation in HD flies. More
      importantly, PINK1 ameliorated ATP levels, neuronal integrity and adult fly
      survival, demonstrating that PINK1 counteracts the neurotoxicity of mHtt. This
      neuroprotection was Parkin-dependent and required mitochondrial outer membrane
      proteins, mitofusin and the voltage-dependent anion channel. Consistent with our
      observations in flies, we demonstrated that the removal of defective mitochondria
      was impaired in HD striatal cells derived from HdhQ111 knock-in mice, and that
      overexpressing PINK1 in these cells partially restored mitophagy. The presence of
      mHtt did not affect Parkin-mediated mitochondrial ubiquitination but decreased
      the targeting of mitochondria to autophagosomes. Altogether, our findings suggest
      that mitophagy is altered in the presence of mHtt and that increasing
      PINK1/Parkin mitochondrial quality control pathway may improve mitochondrial
      integrity and neuroprotection in HD. 

PMID- 25611392
TI  - MiR-34c suppresses tumor growth and metastasis in nasopharyngeal carcinoma by
      targeting MET.
AB  - Our previous microarray analysis indicated that miR-34c was downregulated in
      nasopharyngeal carcinoma (NPC). However, little is known about the function and
      molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be
      significantly downregulated in NPC cell lines and clinical tissues. Ectopic
      expression of miR-34c suppressed NPC cell viability, colony formation, anchorage
      independent growth, cell migration and invasion in vitro, and inhibited xenograft
      tumor growth and lung metastasis in vivo. MET proto-oncogene (MET) was identified
      as a direct target of miR-34c using luciferase reporter assays, quantitative RT
      PCR, western blotting and immunofluorescent staining. Overexpression of miR-34c
      markedly reduced MET expression at both the mRNA and protein levels. Knockdown of
      MET suppressed NPC cell proliferation, migration and invasion, whereas the
      restoration of MET rescued the suppressive effects of miR-34c. The demethylation
      agent 5-aza-2'-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell
      lines. The promoter region of miR-34c was hypermethylated in NPC cells. In
      conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting
      MET. The newly identified miR-34c/MET pathway provides further insights into the
      development and progression of NPC, and may represent a novel therapeutic target
      for NPC treatment. 

PMID- 25611394
TI  - Wrinkling and folding of thin films by viscous stress.
AB  - We examine the buckling of a thin elastic film floating on a viscous liquid layer
      which is itself supported on a prestretched rubber sheet. Releasing the
      prestretch in the rubber induces a viscous stress in the liquid, which in turn
      induces a compressive stress in the elastic film, leading to buckling. Unlike
      many previous studies on wrinkling of floating films, the buckling process in the
      present study is dominated by viscous effects whereas gravitational effects are
      negligible. An approximate shear lag model predicts the evolution of the stress
      profile in the unbuckled film that depends on three parameters: the rate at which
      the prestretch is released, the thickness of the liquid layer, and the length of
      the elastic film. A linear perturbation analysis is developed to predict the
      wavelength of wrinkles. Numerical simulations are conducted to predict nonlinear
      evolution of the wrinkle wavelength and amplitude. Experiments using elastic
      polymer films and viscous polymer liquids show trends that are qualitatively
      consistent with the predictions although quantitatively, the experimentally
      observed wrinkle wavelengths are longer than predicted. Although this article is
      focused only on small-strain wrinkling behavior, we show that application of
      large nominal strains (on the order of 100%) leads to sharply localized folds.
      Thus this approach may be useful for developing buckled features with high aspect
      ratio on surfaces. 

PMID- 25611393
TI  - Loss of anchorage primarily induces non-apoptotic cell death in a human mammary
      epithelial cell line under atypical focal adhesion kinase signaling.
AB  - Anchorage dependence of cellular growth and survival prevents inappropriate cell
      growth or survival in ectopic environments, and serves as a potential barrier to
      metastasis of cancer cells. Therefore, obtaining a better understanding of
      anchorage-dependent responses in normal cells is the first step to understand and
      impede anchorage independence of growth and survival in cancer cells and finally
      to eradicate cancer cells during metastasis. Anoikis, a type of apoptosis
      specifically induced by lack of appropriate cell-extracellular matrix adhesion,
      has been established as the dominant response of normal epithelial cells to
      anchorage loss. For example, under detached conditions, the untransformed mammary
      epithelial cell (MEC) line MCF-10 A, which exhibits myoepithelial
      characteristics, underwent anoikis dependent on classical ERK signaling. On the
      other hand, recent studies have revealed a variety of phenotypes resulting in
      cell death modalities distinct from anoikis, such as autophagy, necrosis, and
      cornification, in detached epithelial cells. In the present study, we
      characterized detachment-induced cell death (DICD) in primary human MECs
      immortalized with hTERT ((Tert)HMECs), which are bipotent progenitor-like cells
      with a differentiating phenotype to luminal cells. In contrast to MCF-10 A cells,
      apoptosis was not observed in detached (Tert)HMECs; instead, non-apoptotic cell
      death marked by features of entosis, cornification, and necrosis was observed
      along with downregulation of focal adhesion kinase (FAK) signaling. Cell death
      was overcome by anchorage-independent activities of FAK but not PI3K/AKT, SRC,
      and MEK/ERK, suggesting critical roles of atypical FAK signaling pathways in the
      regulation of non-apoptotic cell death. Further analysis revealed an important
      role of TRAIL (tumor necrosis factor (TNF)-related apoptosis-inducing ligand) as
      a mediator of FAK signaling in regulation of entosis and necrosis and a role of
      p38 MAPK in the induction of necrosis. Overall, the present study highlighted
      outstanding cell subtype or differentiation stage specificity in cell death
      phenotypes induced upon anchorage loss in human MECs. 

PMID- 25611395
TI  - Primary implantation of type I Boston keratoprosthesis in nonautoimmune corneal
      diseases.
AB  - PURPOSE: The aim of this study was to report outcomes of type I Boston
      keratoprosthesis (KPro) as primary corneal surgery in nonautoimmune corneal
      disorders. METHODS: In this retrospective, observational, large single-center
      case series of 43 eyes (37 patients) that were followed for an average of 39
      months (1-6 years), primary implantation of the type I Boston KPro was performed
      in all patients. Visual acuity at year 1, visual acuity at last follow-up, and
      postoperative complication rates were examined for all eyes. RESULTS:
      Preoperative best-corrected visual acuity ranged from 20/60 to light perception,
      with vision of 20/200 or worse in 88%. Vision was >=20/200 at 1 year in 77% of
      eyes (P < 0.0001). Complications included retroprosthetic membrane formation
      (51%), glaucoma progression (47%), corneal melt (19%), and sterile vitritis
      (14%). CONCLUSIONS: In a large series with long follow-up, primary Boston KPro
      effectively restored vision. Close follow-up is needed to manage the known
      complications after Boston KPro.

PMID- 25611396
TI  - Unusual limbal lesion in neurofibromatosis type 1.
AB  - PURPOSE: To describe an unusual limbal lesion clinically resembling pterygium in
      a young patient with neurofibromatosis type 1. METHODS: Clinical case report with
      a review of the literature. RESULTS: The lesion was excised, and histopathology
      was performed. Histopathology disclosed conjunctival mucosa with expansion of the
      substantia propria by dense and loose collagenous tissue, small nerves, and thin
      walled blood vessels. No skin or skin appendages were seen, although a small
      amount of mature adipose was present. Focally, spindle cells with wavy nuclei
      were seen scattered within the collagenous areas and were positive on S100
      immunohistochemistry. Mast cells were readily identifiable. There was no evidence
      of actinic elastosis, dysplasia, or malignancy. These histopathological features
      most resemble heterotopia with some features of neurofibroma. CONCLUSIONS: We
      report an unusual limbal lesion in a patient with neurofibromatosis type 1.
      Histopathological features resemble a heterotopia with some neurofibroma
      features. We suggest that all lesions excised from patients with
      neurofibromatosis, no matter how characteristic in appearance, be sent for
      histopathological confirmation of diagnosis.

PMID- 25611397
TI  - Topographic and biomechanical evaluation of corneas in patients with ocular
      rosacea.
AB  - PURPOSE: To compare the topographic and biomechanical properties of corneas in
      the eyes of patients with ocular rosacea (OR) with those of healthy individuals.
      METHODS: Thirty-four healthy individuals (control group) and 34 patients with OR
      (study group) were evaluated in this study. Topographic measurements including
      keratometry values, irregularity, and surface asymmetry index in the right eye of
      each participant were obtained using a Scheimpflug camera with a Placido disc
      topographer (Sirius). Corneal hysteresis (CH), corneal resistance factor (CRF),
      corneal-compensated intraocular pressure (IOP), and Goldmann-related IOP were
      measured using the Reichert Ocular Response Analyzer. Central corneal thickness
      was also measured using ultrasonic pachymetry and the Sirius corneal topography
      system. RESULTS: Topographic parameters were not significantly different between
      the groups (P > 0.05). Mean CH and CRF were significantly lower in patients with
      OR (P = 0.003 and 0.001, respectively). Central corneal thickness was
      significantly lower in patients with OR compared with healthy controls (P <
      0.001). Mean Goldmann-related IOP and corneal-compensated IOP were not
      significantly different between the groups (P = 0.09 and 0.13, respectively).
      CONCLUSIONS: This study demonstrated that although the eyes of patients with OR
      had corneal topographic findings similar to those of healthy controls, corneal
      biomechanical measurements (CH and CRF) were significantly lower in patients with
      OR. These results need to be considered when planning corneal refractive surgery
      in patients with OR.

PMID- 25611398
TI  - Can tetracycline antibiotics duplicate the ability of azithromycin to stimulate
      human meibomian gland epithelial cell differentiation?
AB  - PURPOSE: Azithromycin and tetracyclines are commonly prescribed in the United
      States for the treatment of meibomian gland dysfunction (MGD). The efficacy of
      these antibiotics has been believed to be their antiinflammatory and
      antibacterial actions, which suppress MGD-associated posterior blepharitis and
      growth of lid bacteria. However, we recently discovered that azithromycin can act
      directly on human meibomian gland epithelial cells (HMGECs) to stimulate their
      function. In this study, we sought to determine whether tetracycline antibiotics
      can duplicate this azithromycin effect. METHODS: Immortalized HMGEC were cultured
      in the presence of a vehicle, azithromycin, doxycycline, minocycline, or
      tetracycline for 5 days. Cells were evaluated for cholesterol and neutral lipid
      staining, and the lipid composition of cellular lysates was analyzed by high
      performance thin-layer chromatography. RESULTS: Our results demonstrate that
      azithromycin's ability to stimulate the differentiation of human meibomian gland
      cells is unique, and is not duplicated by doxycycline, minocycline, or
      tetracycline. Azithromycin, but not the other antibiotics, significantly
      increased the cellular accumulation of cholesterol, cholesterol esters,
      phospholipids, and lysosomes. These differentiative actions of azithromycin were
      paralleled by an increased expression of sterol regulatory element-binding
      protein 1. CONCLUSIONS: Our findings show that the stimulatory effects of
      azithromycin on HMGEC function are unique and are not duplicated by the
      antibiotics doxycycline, minocycline, or tetracycline. Our results further
      suggest that this stimulatory influence of azithromycin may contribute to its
      beneficial effect in treating MGD and its associated evaporative dry eye disease.

PMID- 25611399
TI  - Detection of fungal hyphae using smartphone and pocket magnifier: going cellular.
AB  - PURPOSE: The aim of this study was to detect fungal hyphae in a corneal scraping
      sample using a cost-effective assembly of smartphone and pocket magnifier.
      METHODS: In this case report, a tissue sample was obtained by conventional
      corneal scraping from a clinically suspicious case of mycotic keratitis. The
      smear was stained with Gram stain, and a 10% potassium hydroxide mount was
      prepared. It was imaged using a smartphone coupled with a compact pocket
      magnifier and integrated light-emitting diode assembly at point-of-care.
      Photographs of multiple sections of slides were viewed using smartphone screen
      and pinch-to-zoom function. The same slides were subsequently screened under a
      light microscope by an experienced microbiologist. The scraping from the ulcer
      was also inoculated on blood agar and Sabouraud dextrose agar. RESULTS:
      Smartphone-based digital imaging revealed the presence of gram-positive organism
      with hyphae. Examination under a light microscope also yielded similar findings.
      Fusarium was cultured from the corneal scraping, confirming the diagnosis of
      mycotic keratitis. The patient responded to topical 5% natamycin therapy, with
      resolution of the ulcer after 4 weeks. CONCLUSIONS: Smartphones can be
      successfully used as novel point-of-care, cost-effective, reliable microscopic
      screening tools.

PMID- 25611400
TI  - Eating Self-Regulation in Overweight and Obese Adults: A Concept Analysis.
AB  - BACKGROUND: Poor eating behaviors greatly influence the development of becoming
      overweight or obese. Learning to better self-regulate eating is one area in which
      individuals can positively influence their own health. PURPOSE: The purpose of
      this concept analysis is to provide an in-depth analysis of the concept eating
      self-regulation as it pertains to overweight and obese adults using Walker and
      Avant's method. RESULTS: The definition for eating self-regulation formulated as
      a result of this concept analysis and based on the critical attributes is the
      ability to initiate goal-related behaviors, to consistently self-monitor dietary
      intake, to regularly apply willpower to resist temptations, to self-evaluate
      where one stands in relationship to goal attainment, and finally to maintain
      motivation to positively change eating behaviors. Cognitive restraint,
      moderation, mindfulness, disinhibition, delayed gratification, emotions and
      moods, self-efficacy, social support, the environment, and physical activity are
      the antecedents that may influence eating self-regulation. CONCLUSION: Examining
      an individual's weight, body mass index, lipid levels, or blood pressure are some
      ways to determine if self-regulation of eating behavior is achieved. With a
      consistent definition of self-regulation and a better understanding of the
      critical factors that influence eating behaviors, research can better explore how
      to help individuals change their eating behaviors more effectively.

PMID- 25611401
TI  - The potential impact of animal protein intake on global and abdominal obesity:
      evidence from the Observation of Cardiovascular Risk Factors in Luxembourg
      (ORISCAV-LUX) study.
AB  - OBJECTIVE: To examine the association of total animal protein intake and protein
      derived from different dietary sources (meat; fish and shellfish; eggs; milk
      products) with global and abdominal obesity among adults in Luxembourg. DESIGN:
      Binary logistic regression analysis was used to assess the relationship between
      animal protein intake (as a percentage of total energy intake) and global obesity
      (BMI >= 30.0 kg/m(2)) and abdominal obesity (waist circumference >= 102 cm for
      men and >= 88 cm for women), after controlling for potential confounders.
      SETTING: Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX)
      study. SUBJECTS: The study population was derived from a national cross-sectional
      stratified sample of 1152 individuals aged 18-69 years, recruited between
      November 2007 and January 2009. RESULTS: There was an independent positive
      association between total animal protein intake and both global (OR = 1.18; 95%
      CI 1.12, 1.25) and abdominal obesity (OR = 1.14; 95% CI 1.08, 1.20) after
      adjustment for age, gender, education, smoking, physical activity and intakes of
      total fat, carbohydrate, fibre, and fruit and vegetables. Protein intakes from
      meat, fish and shellfish were positively associated with global and abdominal
      obesity with further adjustment for vegetal protein and other sources of animal
      derived protein (all P < 0.01). Protein derived from eggs or milk products was
      unrelated to global or abdominal obesity. CONCLUSIONS: Our findings suggest that
      protein derived from animal sources, in particular from meat, fish and shellfish,
      may be associated with increased risk of both global and abdominal obesity among
      presumably healthy adults in Luxembourg. These findings suggest that lower animal
      protein intakes may be important for maintenance of healthy body weight.

PMID- 25611402
TI  - Scheuermann's disease (dysostosis) of the spine.
AB  - A 17-year-old adolescent boy presented with progressive lower back pain and
      fatigue. 

PMID- 25611403
TI  - New resolutions for 2015, but Orthopedics remains clinical, trusted, independent.

PMID- 25611404
TI  - Brace treatment is effective for scoliosis.

PMID- 25611405
TI  - Erratum for "acute pediatric leg compartment syndrome in chronic myeloid
      leukemia".

PMID- 25611406
TI  - Biomechanical analysis of posterior cruciate ligament reconstruction with
      aperture femoral fixation.
AB  - The goal of this study was to determine whether single-tunnel-double-bundle
      equivalent posterior cruciate ligament (PCL) reconstruction using an aperture
      femoral fixation device better replicated normal knee kinematics than single
      bundle reconstruction. Eight fresh-frozen human cadaver knees underwent
      arthroscopically assisted PCL reconstruction and were examined with a robotic
      testing system to assess knee joint kinematics under combinations of applied
      internal, neutral, and external rotational tibial torque and anteroposterior
      translational forces at 0 degrees , 30 degrees , 60 degrees , 90 degrees , and
      120 degrees  flexion. Three conditions were tested: (1) intact PCL; (2) single
      tunnel PCL reconstruction with anterolateral and posteromedial bundle fixation at
      90 degrees /90 degrees  (single bundle); and (3) 90 degrees /0 degrees  (double
      bundle equivalent), respectively. Posterior tibial translation was the primary
      outcome measure. Compared with the intact knee, double-bundle-equivalent
      reconstruction under external tibial torque allowed greater posterior translation
      across the flexion arc as a whole (P=.025) and at 30 degrees  flexion (P=.027)
      when results were stratified by flexion angle. No other kinematic differences
      were found with single-bundle or double-bundle-equivalent fixation, including
      mediolateral translation and both coupled and isolated tibial rotation (P>.05).
      Single-bundle PCL reconstruction closely approximated native knee rotational and
      translational kinematics, whereas double-bundle-equivalent reconstruction
      permitted increased posterior translation with applied external tibial torque,
      particularly at lower flexion angles. Single-bundle PCL reconstruction provides
      knee stability similar to the intact condition, making it a practical alternative
      to conventional double-bundle PCL reconstruction. The authors found that double
      bundle-equivalent reconstruction provided no advantage to justify its clinical
      use.

PMID- 25611407
TI  - Comparison of nonnavigated and 3-dimensional image-based computer navigated
      balloon kyphoplasty.
AB  - Balloon kyphoplasty is a common treatment for osteoporotic and pathologic
      compression fractures. Advantages include minimal tissue disruption, quick
      recovery, pain relief, and in some cases prevention of progressive sagittal
      deformity. The benefit of image-based navigation in kyphoplasty has not been
      established. The goal of this study was to determine whether there is a
      difference between fluoroscopy-guided balloon kyphoplasty and 3-dimensional image
      based navigation in terms of needle malposition rate, cement leakage rate, and
      radiation exposure time. The authors compared navigated and nonnavigated needle
      placement in 30 balloon kyphoplasty procedures (47 levels). Intraoperative 3
      dimensional image-based navigation was used for needle placement in 21 cases (36
      levels); conventional 2-dimensional fluoroscopy was used in the other 9 cases (11
      levels). The 2 groups were compared for rates of needle malposition and cement
      leakage as well as radiation exposure time. Three of 11 (27%) nonnavigated cases
      were complicated by a malpositioned needle, and 2 of these had to be
      repositioned. The navigated group had a significantly lower malposition rate (1
      of 36; 3%; P=.04). The overall rate of cement leakage was also similar in both
      groups (P=.29). Radiation exposure time was similar in both groups (navigated, 98
      s/level; nonnavigated, 125 s/level; P=.10). Navigated kyphoplasty procedures did
      not differ significantly from nonnavigated procedures except in terms of needle
      malposition rate, where navigation may have decreased the need for needle
      repositioning.

PMID- 25611408
TI  - Open subpectoral biceps tenodesis: reliable treatment for all biceps tendon
      pathology.
AB  - Long head of the biceps (LHB) tendon pathology is a common cause of pain in the
      shoulder. Pathology encountered includes biceps tendon tears and tendonitis,
      biceps anchor or superior labral tears, and biceps subluxation or instability.
      Current surgical treatment options for LHB disorders include tenotomy and
      tenodesis. Tenodesis prevents cosmetic deformity and biceps cramping with
      activity. Open subpectoral tenodesis anatomically restores the length-tension
      relationship of the biceps muscle and removes all diseased biceps from the
      bicipital groove. The authors present their technique of open subpectoral
      tenodesis, which demonstrates a high success rate with consistent pain relief and
      dependable fixation.

PMID- 25611409
TI  - A novel reduction technique for elbow dislocations.
AB  - The purpose of this study was to review a novel reduction maneuver for elbow
      dislocations. This was a retrospective review comparing a traditional elbow
      reduction method with a new single-person reduction technique. The reductions
      were performed during a 3-year period. Patients were evaluated in the Emergency
      Department of a large level I trauma center. All patients had posterolateral
      elbow dislocations. Sixteen patients were studied, with 6 in the traditional
      group and 10 in the novel single-person reduction group. All patients had
      successful reductions in the Emergency Department, but 2 of the patients in the
      traditional group were moved to the single-person reduction group after
      unsuccessful attempts. The traditional method required more sedations,
      assistance, and supplies. The authors had no nerve, vascular, or iatrogenic
      fractures in their series, and the technique was performed by 1 person without
      additional equipment. This technique is a valid option for orthopedic surgeons
      treating elbow dislocations.

PMID- 25611410
TI  - Multiligamentous knee injury concomitant with a patellar tendon rupture.
AB  - Multiligamentous knee injuries with simultaneous patellar tendon ruptures are
      rare. Surgeons must be prepared to address injured structures of the knee to
      allow return of knee function. Restoring motion while protecting repairs is
      important. The authors present 2 cases and discuss treatment strategy for
      preoperative evaluation, surgical intervention, and postoperative care.

PMID- 25611412
TI  - Thumb proximal phalanx reconstruction with nonvascularized corticocancellous
      olecranon bone graft.
AB  - Large segmental bone defects of the phalanges reportedly have been treated with
      free vascularized grafts from the hand, foot, or knee, or with nonvascularized
      grafts from the iliac crest. A nonvascularized structural corticocancellous graft
      from a local site would be advantageous. The olecranon has been used as a source
      of both cancellous and corticocancellous graft. The authors describe a unique
      case of the use of nonvascularized corticocancellous olecranon bone graft for
      structural purposes in a mutilating thumb injury. The patient injured the left
      thumb with a miter saw, resulting in a large degloving wound over a severely
      comminuted fracture of the proximal phalanx, with segmental bone loss between a
      base fragment and displaced condylar fragments. Provisional pin fixation was
      performed at the time of initial emergent irrigation and debridement, along with
      repairs of the extensor pollicis longus, radial digital nerve, and dorsal digital
      nerve. This was followed 3 weeks later by non-vascularized corticocancellous bone
      grafting from the olecranon to the proximal phalanx under regional anesthesia.
      The thumb was mobilized at 11 weeks, and solid union was radiographically
      confirmed at 6 months. The patient achieved moderate active range of motion and
      was able to return to work as a physical therapist. The elbow healed uneventfully
      and without pain or fracture at the donor site. This case shows that robust
      structural bone graft for the phalanges may be obtained from the nearby
      olecranon, under regional anesthesia, without microsurgery, and with potential
      advantages over the iliac crest.

PMID- 25611411
TI  - The hip-spine connection: understanding its importance in the treatment of hip
      pathology.
AB  - EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be
      able to: 1. Discuss the kinematic relationship between the hip and lumbar spine.
      2. Explain the innervation of the hip and lumbar spine and how they relate to one
      another. 3. Recognize the effect of hip disease on the lumbar spine in an
      athletic population, prior to the onset of degenerative changes. 4. Describe an
      algorithm for diagnosis and treatment of patients who present with concomitant
      hip and lumbar spine pain. The hip and lumbar spine are closely related and can
      create similar patterns of pain and dysfunction. Diagnosis and treatment of hip
      and spine-related conditions can be challenging due to symptom overlap.
      Successful evaluation and treatment of hip and lumbar spine conditions requires a
      thorough understanding the hip-spine connection. Historically the hip-spine
      connection has been considered in the context of arthrosis; however, the hip
      spine connection also needs to be considered in a younger athletic population.
      The purpose of this review is to describe the hip-spine connection, discuss the
      clinical implications of this connection, and offer an approach to diagnosis and
      treatment.

PMID- 25611413
TI  - Does intraoperative fluoroscopy improve component positioning in total hip
      arthroplasty?
AB  - Accurate placement of components is imperative for successful outcomes after
      total hip arthroplasty (THA). Although technology-assisted techniques offer the
      potential for greater accuracy in prosthesis positioning, the need for additional
      resources prevents their widespread use. The goal of this study was to compare
      primary THA procedures performed with and without intraoperative fluoroscopic
      guidance with regard to accuracy of prosthesis placement, operative time, and
      postoperative complications. The authors reviewed 341 consecutive cases (330
      patients) undergoing primary THA at the authors' institution from September 2007
      to January 2010. Postoperative anteroposterior radiographs were used to measure
      acetabular inclination angle, leg length discrepancy, and femoral offset
      discrepancy. Operative time and postoperative complications related to implant
      positioning were recorded. Mean acetabular inclination angle, leg length
      discrepancy, and offset discrepancy for control vs study groups were 43.0 degrees
      (range, 32.2 degrees -61.4 degrees ) vs 43.8 degrees  (range, 29.0 degrees -55.1
      degrees ), 4.75 mm (range, 0-25) vs 4.24 mm (range, 0-27), and 8.47 mm (range, 0
      9.7) vs 7.70 mm (range, 0-31), respectively. Complication rates were not
      significantly different between the control (8.1%) and study (5.3%) groups. Mean
      operative time was significantly higher in the study group compared with the
      control group (59.8 vs 52.8 minutes) (P<.0001). The findings showed that
      intraoperative fluoroscopy may not improve prosthesis accuracy or decrease
      postoperative complication rates compared with a freehand technique. Because of
      significantly increased operative time and cost associated with fluoroscopic
      guidance, the authors discourage the use of this technique in uncomplicated
      primary THA performed at high-volume arthroplasty institutions.

PMID- 25611414
TI  - Epidemiology of Kienbock's disease in middle-aged and elderly Japanese women.
AB  - Little research has been done on the prevalence of Kienbock's disease, and there
      is no consensus on the relationship between Kienbock's disease and negative ulnar
      variance. The goal of this cross-sectional study was to determine the prevalence
      of Kienbock's disease in middle-aged and elderly Japanese women and to clarify
      the relationship between Kienbock's disease and negative ulnar variance. The
      authors analyzed plain radiographs of both hands in women 40 years and older
      residing in the community to investigate the prevalence of Kienbock's disease and
      the relationship between Kienbock's disease and negative ulnar variance.
      Kienbock's disease was seen in 7 of the 572 participants. In the group with
      Kienbock's disease, ulnar variance did not differ significantly between affected
      (0.3 mm; SD, 1.5) and unaffected (0.3 mm; SD, 1.0; P=.285) sides. No significant
      difference was seen in ulnar variance values between the affected side in the
      group with Kienbock's disease and the normal group (P=.118). The number or
      proportion of participants with negative ulnar variance did not differ
      significantly between the affected side in the group with Kienbock's disease (3
      of 7) and the unaffected side in the group with Kienbock's disease (1 of 7;
      P=.237) and between the affected side in the group with Kienbock's disease and
      the normal group (111 of 504; P=.189) by chi-square test. The prevalence of
      Kienbock's disease was 1.2% in middle-aged and elderly Japanese women. Negative
      ulnar variance is not a contributing factor to Kienbock's disease.

PMID- 25611415
TI  - Effects of repetitive platelet-rich plasma application on human tenocyte
      proliferation.
AB  - Current clinical application of platelet-rich plasma is showing a trend toward
      multiple treatments. The goal of this study was to show the benefit of interval
      platelet-rich plasma application in the healing and recovery of human tenocytes
      using an in vitro cell model. Eight volunteers (6 men and 2 women) were included
      in this study (mean+/-SD age, 31.6+/-10.9 years). Venous blood was collected from
      new blood draws at 3 different times. Two blood products were prepared on each
      day of treatment: platelet-rich plasma derived from a single-spin process (PRPSS)
      and platelet-rich plasma derived from a double-spin process (PRPDS). The study
      had 2 limbs: 2-day and 4-day intervals. Cell proliferation, measured as
      disintegrations per minute, was then examined via a radioactive thymidine assay.
      In the 2-day-interval group, the difference in disintegrations per minute between
      days 0 and 2 in the PRPSS group reached statistical significance (P =.006). In
      the PRPDS group, statistical difference was seen between days 0 and 4 (P=.001)
      and between days 2 and 4 (P=.030). In the 4-day-interval group, the difference in
      disintegrations per minute between days 4 and 8 in the PRPSS group reached
      statistical significance, showing a decrease in cell proliferation (P =.013). In
      the PRPDS group, a statistical difference was seen between days 0 and 8 (P=.021),
      also showing a decrease in cell proliferation. The greatest effect of platelet
      rich plasma, which has a positive effect on tenocyte proliferation and recovery,
      is seen on initial application. Its effect is diminished with repetitive
      application, and this finding leads to questioning of the efficacy of interval
      platelet-rich plasma dosing.

PMID- 25611416
TI  - Local administration of zoledronic acid for giant cell tumor of bone.
AB  - Giant cell tumor of bone is a locally aggressive tumor with a high local
      recurrence rate. Several adjuvant therapies have been employed to reduce the
      recurrence rate, but their effectiveness remains controversial. The authors
      attempted local administration of zoledronic acid, a nitrogen-containing
      bisphosphonate that strongly inhibits bone resorption, as an adjuvant treatment
      for histologically proven giant cell tumor of bone in 5 patients at their
      institution. After biopsy, 4 patients were treated with local administration of
      zoledronic acid with artificial bone and 1 was treated with zoledronic acid
      without artificial bone. Histologic response to the treatment was evaluated with
      surgically resected specimens. The 4 patients treated with artificial bone showed
      local control, with histologic tumor necrosis rates of 90%, 90%, 50%, and 10%.
      Magnetic resonance imaging showed poor gadolinium enhancement, and histologic
      examination after local zoledronic acid treatment showed tumor necrosis. One
      patient without artificial bone showed no histologic tumor necrosis and had local
      recurrence in soft tissue 18 months after tumor resection. A 3-week waiting
      period between biopsy and zoledronic acid treatment appears reasonable from the
      histological study. Complication of this therapy was delayed wound healing and it
      occurred in 2 cases. Taken together, this case series suggests that local
      administration of zoledronic acid with artificial bone is a potential adjuvant
      therapy for giant cell tumor of bone. On the other hand, effective local
      administration of zoledronic acid requires some bone matrix, including artificial
      bone. Campanacci's grading is important for predicting the effect of local
      administration of zoledronic acid.

PMID- 25611417
TI  - Predictive value of robotic-assisted total hip arthroplasty.
AB  - Acetabular cup positioning, leg-length discrepancy, and global offset are
      important parameters associated with outcomes following total hip arthroplasty
      (THA). Deviation from an accepted range of values can lead to significant
      complications, including dislocation, leg-length discrepancy, impingement,
      accelerated bearing surface wear, and revisions. The purpose of this study was to
      assess whether robotic-assisted THA was reliable in predicting radiographic
      measurements of cup inclination and anteversion, leg-length change, and global
      offset change. All 61 robotic-assisted THAs that met the inclusion and exclusion
      criteria were performed by a single surgeon through a mini-posterior approach.
      Data provided by the robot were collected prospectively, and radiographic data
      were collected retrospectively by 2 blinded independent reviewers. The cohort in
      this study consisted of 27 male and 34 female patients, with an average age of
      60.5 years. A strong inter- and intraobserver correlation was found for the
      radiographic measurements of cup inclination, cup anteversion, leg-length
      discrepancy, and global offset (r>0.8 with P<.001 for all). Ninety-six point
      seven percent of robotic-measured inclination angles and 98.4% of robotic
      measured anteversion angles were within 10 degrees  of radiographic measurements.
      One hundred percent of robotic-measured leg-length change and 91.8% of robotic
      measured global offset change were within 10 mm of radiographic measurements.
      Robotic-assisted THA showed good predictive value for cup inclination and
      anteversion angles and measurements of leg-length change and global offset change
      done postoperatively on plain radiographs. Further refinement of the robotic
      system would make it more accurate in predicting the postoperative parameters
      mentioned.

PMID- 25611418
TI  - Long-term results of shoulder hemiarthroplasty in patients with rheumatoid
      arthritis.
AB  - Rheumatoid arthritis affecting the shoulder is typically associated with
      destruction of the glenohumeral joint and rotator cuff impairment, which can
      result in severe glenoid erosion. Following hemiarthroplasty, severe glenoid
      erosion has also frequently been observed. The authors' aim was to
      retrospectively evaluate the outcome of cemented shoulder hemiarthroplasty in
      patients with rheumatoid arthritis. The authors performed 45 cemented
      hemiarthroplasties in 36 patients with rheumatoid arthritis involving the
      shoulder as well as associated rotator cuff compromise between 1995 and 2008. All
      patients were analyzed radiologically and clinically using patient-reported
      outcome measures. Mean+/-SD visual analog pain scale score was 3+/-2. Mean+/-SD
      Constant score was 55+/-16. Mean+/-SD validated Dutch version of the Disabilities
      of the Arm Shoulder and Hand (DASH) score was 42+/-19. No radiograph showed
      loosening of the implant at follow-up. One patient needed an arthrotomy and
      capsulotomy because of persistent pain and limited range of motion. Tissue
      cultures taken during this second operation were negative for infection. No major
      revision surgery was necessary within the follow-up period. Cemented
      hemiarthroplasty is a viable treatment option for glenohumeral arthritis in
      patients with rheumatoid arthritis. Long-term results show acceptable results and
      low complication rates in this case series for this specific group. A randomized,
      controlled trial comparing hemiarthroplasty, total shoulder arthroplasty, and
      reverse shoulder arthroplasty is necessary to draw definite conclusions in this
      specific patient population.

PMID- 25611419
TI  - Functional outcomes of simultaneous bilateral versus unilateral total knee
      arthroplasty.
AB  - Many patients in need of total knee arthroplasty (TKA) have bilateral symptoms
      and require surgery to both extremities. Performance of a bilateral procedure
      under a single anesthetic provides a reduced hospitalization time, an isolated
      anesthesia risk, a single rehabilitation, and substantial cost savings. While
      most current research examines postoperative complication rates, the primary
      purpose of TKA is the alleviation of pain and improved quality of life. The
      purpose of this study was to assess pain and functional outcomes associated with
      simultaneous bilateral TKA. The authors believe that patients with advanced
      destructive arthritis to numerous joints cannot achieve complete restoration of
      their functional status until comprehensive treatment of their disease process
      occurs. A retrospective review of 697 TKAs in 511 consecutive patients with
      bilateral knee arthritis was performed. Patients underwent either simultaneous
      bilateral TKA (n=186), performed sequentially under the same anesthetic, or
      unilateral TKA (n=325). The same intra- and postoperative protocols were followed
      in each group. There was no statistically significant difference in postoperative
      pain, represented by Knee Society Score (P=.161). However, there was a
      significantly higher postoperative functional outcomes-including increased total
      range of motion (P=.001), flexion (P=.003), and function score (P<.001)
      associated with bilateral TKA. Simultaneous bilateral TKA is an effective
      treatment option and may be worth possible added risk in appropriate patients
      because it produces a better functional outcome.

PMID- 25611420
TI  - Subpectoral biceps tenodesis for bicipital tendonitis with SLAP tear.
AB  - The purpose of this study was to evaluate the outcomes of patients undergoing
      subpectoral biceps tenodesis for bicipital tendonitis with a superior labral
      anterior-posterior (SLAP) tear. Patients undergoing primary subpectoral biceps
      tenodesis for arthroscopically confirmed SLAP tears with signs or findings of
      bicipital tendonitis were included. An independent observer collected data
      prospectively as part of a data repository, which was then analyzed
      retrospectively. Primary outcome measures were the American Shoulder and Elbow
      Surgeons (ASES) score and pain relief via visual analog scale (VAS). Secondary
      outcome measures included the Simple Shoulder Test (SST), Constant, Single
      Assessment Numeric Evaluation (SANE), and Short Form 12 (SF-12) scores. Twenty
      eight patients with a mean+/-SD age of 43.7+/-13.4 years and a mean+/-SD follow
      up of 2.0+/-1.0 years met inclusion criteria. Workers' compensation was involved
      with 43% of cases, and 46% of the included patients were manual laborers. Eight
      (32%) patients were athletes, and 88% of the athletes were overhead athletes.
      Intraoperatively, 15 (54%) patients had type I SLAP tears, 10 (36%) had type II
      SLAP tears, 1 (3%) had a type III SLAP tear, and 2 (7%) had type IV SLAP tears.
      Significant improvements were seen in the following outcome measures pre- vs
      postoperatively: ASES score (58+/-23 vs 89+/-18; P=.001), SST score (6.3+/-3.6 vs
      10.6+/-3.3; P=.001), SANE score (54+/-24 vs 88+/-25; P=.003), VAS score (3.8+/
      2.0 vs 1.1+/-1.8; P=.001), SF-12 overall score (35+/-6 vs 42+/-6; P=.001), and SF
      12 physical component score (39+/-6 vs 50+/-10; P=.001). Overall satisfaction was
      excellent in 80% of patients. Subpectoral biceps tenodesis demonstrates excellent
      clinical outcomes in select patients with SLAP tears. [Orthopedics. 2015;
      38(1):e48-e53.]. 

PMID- 25611421
TI  - Benefit of degenerative posterior longitudinal ligament removal during anterior
      decompression in cervical spondylotic myelopathy.
AB  - It remains controversial whether degenerative posterior longitudinal ligaments
      should be removed during anterior decompression procedures for cervical
      spondylotic myelopathy. Few data are available from studies that have compared
      removing and retaining the degenerative posterior longitudinal ligament. The goal
      of this retrospective study was to evaluate the benefit of degenerative posterior
      longitudinal ligament removal during such operations. Clinical data on 130
      patients with confirmed degenerative posterior longitudinal ligament who
      underwent anterior cervical decompression surgery were retrospectively reviewed.
      All procedures were performed by the same senior orthopedic surgeon at the
      authors' spinal surgery center. The degenerative posterior longitudinal ligament
      was removed in 62 patients (group A) and retained in 68 patients (group B). The
      130 patients were followed for 36 months. The Japanese Orthopedic Association
      score improved from 9.0+/-2.7 to 14.7+/-1.5 in group A and from 9.4+/-2.6 to
      14.1+/-1.7 in group B (P=.028). The recovery rate for spinal cord neurologic
      function was 66.7% in group A and 61.3% in group B (P=.031). Operating time was
      longer (P=.002) and the sagittal median diameter of the vertebral canal was
      enhanced in group A (P<.001). Narrowing of previously enlarged canals occurred at
      a significantly higher rate in group B (P=.044). No significant difference was
      found in the rates of common complications between groups. Removal of the
      degenerative posterior longitudinal ligament in anterior decompression procedures
      for cervical spondylotic myelopathy appeared to be beneficial and provided more
      complete decompression and better postoperative outcomes than surgery without
      removal of the ligament. Although this procedure was generally safe, it required
      longer operating times, was more technically challenging, and required more
      experienced surgeons than surgery without removal of the ligament.

PMID- 25611422
TI  - Odyssey of an elbow synovial chondromatosis.
AB  - Synovial chondromatosis of the elbow is an uncommon condition. However, a
      chondrosarcoma arising from the former is remarkably rare. The authors report a
      case of an elbow chondrosarcoma secondary to synovial chondromatosis in a 38-year
      old woman. Before the development of chondrosarcoma, the patient underwent 3
      operations and 3 sessions of radiosynovectomy because of continuous recurrence of
      synovial chondromatosis on the left elbow. After the last radiosynovectomy,
      magnetic resonance imaging and biopsy showed a grade II chondrosarcoma secondary
      to synovial chondromatosis. The patient underwent further surgery and custom-made
      arthroplasty because of aseptic loosening of the prosthesis. Four months after
      the last intervention, 3 subcutaneous nodes appeared on the patient's elbow and
      were histologically found to be a recurrence of chondrosarcoma (grade III).
      Amputation by disarticulation of the shoulder was performed in addition to biopsy
      of another subcutaneous node on the abdomen. The biopsy showed metastasis of
      chondrosarcoma. At final follow-up, the patient had lung metastasis 7 years after
      the initial diagnosis. A reason for the manifestation of primary synovial
      chondromatosis and its progression to chondrosarcoma has not been found. Synovial
      chondromatosis progressing to chondrosarcoma in the elbow was reported in only 1
      case, with no clear initial diagnosis. The role of radiosynovectomy in the
      development of chondrosarcoma is unknown, and no reports have described the
      treatment of elbow synovial chondromatosis. Although synovial chondromatosis is
      benign, its metaplastic nature is a marker of possible malignancy, especially
      with signs of recurrence and aggression. The role of radiosynovectomy in
      malignant changes should be examined in future studies.

PMID- 25611423
TI  - Posterior interosseous nerve incarceration with endobutton repair of distal
      biceps.
AB  - Distal biceps ruptures are uncommon injuries that comprise approximately 3% of
      all biceps pathology. This injury is most commonly seen in 40- to 60-year-old
      men, and the mechanism of injury involves a forceful extension movement to a
      flexed elbow. Without surgical intervention, patients are left with measurable
      weakness in elbow flexion and supination as well as a cosmetic deformity that
      often leaves them dissatisfied. Consequently, early surgical repair is advocated
      for physically active individuals. A variety of surgical approaches and fixation
      devices are currently used for distal biceps repair. The single-incision cortical
      button repair for distal biceps avulsions has become popular since Bain
      introduced the technique in 2000. The advantage of the cortical button biceps
      repair technique is the significantly higher failure strength than either the 2
      incision technique or the suture anchor repair. The initial repair strength of
      the cortical button technique allows immediate active elbow range of motion and
      accelerated rehabilitation. Additionally, the single-incision anterior approach
      is less invasive than the 2-incision biceps repair and results in a lower
      incidence of heterotopic ossification. One disadvantage of this approach,
      however, is the risk of injury to the posterior interosseous nerve. The authors
      report a case in which the posterior interosseous nerve was incarcerated between
      the cortical button and the radius during acute distal biceps repair, resulting
      in complete posterior interosseus nerve palsy. This case report details the
      surgery leading to the nerve palsy and the subsequent nerve exploration that
      identified the cause of the nerve palsy. Recommendations are made on how to avoid
      this complication during distal biceps tendon repairs.

PMID- 25611424
TI  - Readmission within 30 days of discharge after hip fracture care.
AB  - The Affordable Care Act currently requires hospitals to report 30-day readmission
      rates for certain medical conditions. It has been suggested that surveillance
      will expand to include hip and knee surgery-related readmissions in the future.
      To ensure quality of care and avoid penalties, readmissions related to hip
      fractures require further investigation. The goal of this study was to evaluate
      factors associated with 30-day hospital readmission after hip fracture at a level
      I trauma center. This retrospective cohort study included 1486 patients who were
      65 years or older and had a surgical procedure performed to treat a femoral neck,
      intertrochanteric, and/or subtrochanteric hip fracture during an 8-year period.
      Analysis of these patients showed a 30-day readmission rate of 9.35% (n=139).
      Patients in the readmission group had a significantly higher rate of pre-existing
      diabetes and pulmonary disease and a longer initial hospital length of stay.
      Readmissions were primarily the result of medical complications, with only one
      fourth occurring secondary to orthopedic surgical failure. Pre-existing pulmonary
      disease (odds ratio [OR], 1.885; 95% confidence interval [CI], 1.305-2.724),
      initial hospitalization of 8 days or longer (OR, 1.853; 95% CI, 1.223-2.807), and
      discharge to a skilled nursing facility (OR, 1.586; 95% CI, 1.043-2.413) were
      determined to be predictors of readmission. Accordingly, patient management
      should be consistently geared toward optimizing chronic disease states while
      concomitantly working to minimize the duration of initial hospitalization and
      decrease readmission rates

PMID- 25611425
TI  - Median nerve superficial to the transverse carpal ligament.
AB  - Recurrent carpal tunnel syndrome occurs in up to 12% of cases after carpal tunnel
      release. Recurrent carpal tunnel syndrome is defined as recurrence of classic
      symptoms confirmed by electrodiagnostic studies after a symptom-free interval of
      a minimum of 6 months, as opposed to persistent carpal tunnel syndrome, where a
      symptom-free interval never occurs after carpal tunnel release, which is
      attributed to incomplete release of the transverse carpal ligament. The most
      common causes of recurrent carpal tunnel syndrome requiring reoperation are
      incomplete release of the transverse carpal ligament and scarring of the median
      nerve to the surrounding structures. Surgical exploration, release of the
      reconstituted transverse carpal ligament, and freeing of the median nerve from
      constricting scar will usually result in symptom relief. The authors describe an
      unusual presentation of recurrent carpal tunnel syndrome with healing of the
      transverse carpal ligament dorsal to the median nerve, trapping the median nerve
      in the subcutaneous tissue. Hand surgeons must be aware of this anomalous
      location when performing revision carpal tunnel release. The surgeon must locate
      the median nerve proximally in normal tissue before proceeding distally to avoid
      iatrogenic injury during revision carpal tunnel release.

PMID- 25611426
TI  - Pertrochanteric hip fracture: a "routine" fracture with a potentially devastating
      vascular complication.
AB  - Vascular injuries in conjunction with low-energy geriatric hip fractures,
      although uncommon, can be life-threatening. Furthermore, vascular injuries are
      usually iatrogenic, related to malpositioning of percutaneous reduction aids,
      aberrant drilling, or poorly sized implants. The authors describe an older woman
      who had a low-energy pertrochanteric hip fracture. She was noted preoperatively
      to have an isolated decrease in hemoglobin of 4.7 g/dL in the 2.5 days before
      surgery. Fracture reduction was performed with closed and percutaneous techniques
      with the limb free-legged on a radiolucent flat-top table. On reduction of the
      distal fragment (which was translated proximal and medial), extremely brisk
      bleeding was noted from the fracture site. Vascular control was obtained with
      subvastus exposure through the fracture site to gain access to the medial aspect
      of the thigh. A pulsatile traumatic laceration in the profunda femoral artery was
      identified, and the ends were ligated. The fracture was then fixated internally.
      Careful analysis of preoperative imaging showed the distal fracture fragment in
      immediate proximity to the calcified profunda femoral artery, transecting it at
      the time of injury and resulting in the significant increase in hemoglobin noted
      preoperatively. This case is an unusual vascular injury associated with a very
      common geriatric fracture pattern. To the authors' knowledge, there are only 2
      cases in the English language literature of acute vascular injury as a result of
      a proximal femur fracture fragment. Given the routine nature of geriatric hip
      fractures, the orthopedic surgeon must be familiar with the appropriate diagnosis
      and management of this major complication.

PMID- 25611428
TI  - All-trans-retinoic Acid differentially regulates proliferation of normal and
      leukemic B cells from different subsets of chronic lymphocytic leukemia.
AB  - All-trans-retinoic acid (ATRA) has been shown to modulate cell growth and
      differentiation in a variety of tumor cell types, but little is known regarding
      its precise role in regulation of leukemic B cells from different subsets of
      chronic lymphocytic leukemia (CLL). Previously, we showed that IL-21
      significantly inhibits the CpG-mediated proliferation of CLL B cells in
      progressive compared to nonprogressive patients. In the present study, the effect
      of ATRA (10(-7) mol/L) on in vitro proliferation and apoptosis of B cells was
      investigated in 24 CLL patients and 8 normal subjects. Our results showed that
      ATRA markedly enhanced CpG-mediated proliferation of normal B cells, but it
      slightly inhibited CpG-induced proliferation of CLL B cells [stimulation index
      (SI): 105.6 vs. 14.7, P = 0.0001]. Although addition of IL-21 counteracted the
      proliferative effect of ATRA in normal B cells, it significantly enhanced the
      growth of tumor B cells in presence of CpG and ATRA. This stimulatory effect was
      restricted to nonprogressive and unmutated patients compared to progressive and
      mutated groups, respectively. Our results suggest that ATRA acts differentially
      on normal and CLL B cells and might have therapeutic implication in patients with
      progressive disease.

PMID- 25611429
TI  - Three-dimensional activated graphene network-sulfonate-terminated polymer
      nanocomposite as a new electrode material for the sensitive determination of
      dopamine and heavy metal ions.
AB  - We report here that three-dimensional activated graphene networks (3DAGNs) are a
      better matrix to prepare graphene-polymer nanocomposites for sensitive
      electroanalysis than two-dimensional graphene nanosheets (2DGNs). 3DAGNs were
      synthesized in advance by the direct carbonization and simultaneous chemical
      activation of a cobalt ion-impregnated D113-type ion exchange resin, which showed
      an interconnected network structure and a large specific surface area. Then, the
      3DAGN-sulfonate-terminated polymer (STP) nanocomposite was prepared via the in
      situ chemical co-polymerization of m-aminobenzene sulfonic acid and aniline in
      the presence of 3DAGNs. The 3DAGN-STP nanocomposite can adsorb dopamine (DA) and
      heavy metal ions, which was confirmed by quartz crystal microbalance studies. The
      3DAGN-STP modified glassy carbon electrode (GCE) was used for the electrochemical
      detection of DA in the presence of ascorbic acid and uric acid, with a linear
      response range of 0.1-32 MUM and a limit of detection of 10 nM. In addition,
      differential pulse voltammetry was used for the simultaneous determination of
      Cd(2+) and Pb(2+) at the 3DAGN-STP/GCE further modified with a bismuth film,
      exhibiting linear response ranges of 1-70 MUg L(-1) for Cd(2+) and 1-80 MUg L(-1)
      for Pb(2+) with limits of detection of 0.1 MUg L(-1) for Cd(2+) and 0.2 MUg L(-1)
      for Pb(2+). Because the 3DAGN-STP can integrate the advantages of 3DAGNs with
      STPs, the 3DAGN-STP/GCE was more sensitive than the bare GCE, 3DAGN/GCE, and 2DGN
      STP/GCE for the determination of DA and heavy metal ions. 

PMID- 25611430
TI  - Complete catalytic cycle of cofactor-independent phosphoglycerate mutase involves
      a spring-loaded mechanism.
AB  - Cofactor-independent phosphoglycerate mutase (iPGM), an important enzyme in
      glycolysis and gluconeogenesis, catalyses the isomerization of 2- and 3
      phosphoglycerates by an Mn(2+)-dependent phospho-transfer mechanism via a phospho
      enzyme intermediate. Crystal structures of bi-domain iPGM from Staphylococcus
      aureus, together with substrate-bound forms, have revealed a new conformation of
      the enzyme, representing an intermediate state of domain movement. The substrate
      binding site and the catalytic site are present in two distinct domains in the
      intermediate form. X-ray crystallography complemented by simulated dynamics has
      enabled delineation of the complete catalytic cycle, which includes binding of
      the substrate, followed by its positioning into the catalytic site, phospho
      transfer and finally product release. The present work describes a novel
      mechanism of domain movement controlled by a hydrophobic patch that is exposed on
      domain closure and acts like a spring to keep the protein in open conformation.
      Domain closing occurs after substrate binding, and is essential for phospho
      transfer, whereas the open conformation is a prerequisite for efficient substrate
      binding and product dissociation. A new model of catalysis has been proposed by
      correlating the hinge-bending motion with the phospho-transfer mechanism.

PMID- 25611431
TI  - Surgical stress induces brain-derived neurotrophic factor reduction and
      postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation
      in aged mice.
AB  - AIMS: This study explored whether surgical stress-induced glucocorticoid receptor
      (GR) phosphorylation is related to postoperative cognitive dysfunction (POCD) in
      aged individuals. Inhibition of GR activation could be an effective treatment for
      POCD. METHODS: A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6
      months old. Animals in control group were treated in identical manners except for
      laparotomy. Cognitive function was evaluated by Morris water maze and elevated
      plus maze. Western blot and Elisa assay were used to detect related molecules.
      Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation.
      RESULTS: The cognitive function was impaired, and brain-derived neurotrophic
      factor (BDNF) was found reduced in aged POCD group. GR translocation into nucleus
      and elevated GR phosphorylation were found in prefrontal cortex of aged POCD
      mice. Cyclin-dependent Kinase 5 (CDK5), kinase for GR phosphorylation also
      elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of
      BDNF and cognitive dysfunction in aged mice were both rescued. CONCLUSION: These
      results presented a mechanism that surgical stress-induced GR phosphorylation
      contributes to POCD in aged individuals. Inhibition of GR activation and
      phosphorylation might be a potential treatment target of POCD.

PMID- 25611432
TI  - Interleukin-8: A critical chemokine in biliary atresia.
AB  - Biliary atresia (BA) is characterized by periductular inflammation and fibrosis
      and is associated with the progressive obliteration of the bile ducts. The
      induction and maintenance of systemic and local inflammatory responses plays a
      pivotal role in this process. Interleukin-8 (IL-8) is an important mediator of
      inflammation and the immune response in human disease. IL-8 is overexpressed in
      BA, and its expression positively correlates with inflammation and liver
      fibrosis. In this review, we focus on the available evidence, recent insights,
      and future clinical and preclinical possibilities regarding the role of IL-8 in
      BA. 

PMID- 25611433
TI  - AICAR attenuates organ injury and inflammatory response after intestinal ischemia
      and reperfusion.
AB  - Intestinal ischemia and reperfusion (I/R) is encountered in various clinical
      conditions and contributes to multiorgan failure and mortality as high as 60% to
      80%. Intestinal I/R not only injures the intestine, but affects remote organs
      such as the lung leading to acute lung injury. The development of novel and
      effective therapies for intestinal I/R are critical for the improvement of
      patient outcome. AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside) is a cell
      permeable compound that has been shown to possess antiinflammatory effects. The
      objective is to determine that treatment with AICAR attenuates intestinal I/R
      injury and subsequent acute lung injury (ALI). Male Sprague Dawley rats (275 to
      325 g) underwent intestinal I/R injury with blockage of the superior mesenteric
      artery for 90 min and subsequent reperfusion. At the initiation of reperfusion,
      vehicle or AICAR (30 mg/kg BW) was given intravenously (IV) for 30 min. At 4 h
      after reperfusion, blood and tissues were collected for further analyses.
      Treatment with AICAR significantly decreased the gut damage score and the water
      content, indicating improvement in histological integrity. The treatment also
      attenuated tissue injury and proinflammatory cytokines, and reduced bacterial
      translocation to the gut. AICAR administration after intestinal I/R maintained
      lung integrity, attenuated neutrophil chemotaxis and infiltration to the lungs
      and decreased lung levels of tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-6. Inflammatory mediators, lung-inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) proteins, were decreased in the lungs and lung apoptosis
      was significantly reduced after AICAR treatment. These data indicate that AICAR
      could be developed as an effective and novel therapeutic for intestinal I/R and
      subsequent ALI. 

PMID- 25611434
TI  - Extracellularly Extruded Syntaxin-4 Is a Potent Cornification Regulator of
      Epidermal Keratinocytes.
AB  - In the skin epidermis, keratinocytes undergo anchorage-dependent cornification,
      which gives rise to stratified multilayers, each with a distinct differentiation
      feature. The active formation of the cornified cell envelope (CCE), an important
      element in the skin barrier, occurs in keratinocytes of the upper epidermal
      layers and impacts their terminal differentiation. In the present study, we
      identified the extracellularly extruded syntaxin-4 as a potent differentiation
      regulator of epidermal keratinocytes. We found that differentiation stimuli led
      to the acceleration of syntaxin-4 exposure at the keratinocyte cell surface and
      that the artificial control of extracellular syntaxin-4, either by the forced
      expression of several syntaxin-4 mutants with structural alterations at the
      putative functional core site (AIEPQK), or by using antagonistic circular
      peptides containing this core sequence, dramatically influenced the CCE
      formation, with spatial misexpression of TGase1 and involucrin. We also found
      that the topical application of a peptide that exerted the most prominent
      antagonistic activity for syntaxin-4, named ST4n1, evidently prevented the
      formation of the hyperplastic and hyperkeratotic epidermis generated by physical
      irritation in HR-1 mice skin. Collectively, these results demonstrate that
      extracellularly extruded syntaxin-4 is a potent regulator of CCE differentiation,
      and that ST4n1 has potential as a clinically applicable reagent for keratotic
      skin lesions. 

PMID- 25611435
TI  - Rewiring of sIgM-Mediated Intracellular Signaling through the CD180 Toll-like
      Receptor.
AB  - Chronic lymphocytic leukemia (CLL) development and progression are thought to be
      driven by unknown antigens/autoantigens through the B cell receptor (BCR) and
      environmental signals for survival and expansion including toll-like receptor
      (TLR) ligands. CD180/RP105, a membrane-associated orphan receptor of the TLR
      family, induces normal B cell activation and proliferation and is expressed by
      approximately 60% of CLL samples. Half of these respond to ligation with anti
      CD180 antibody by increased activation/phosphorylation of protein kinases
      associated with BCR signaling. Hence CLL cells expressing both CD180 and the BCR
      could receive signals via both receptors. Here we investigated cross-talk between
      BCR and CD180-mediated signaling on CLL cell survival and apoptosis. Our data
      indicate that ligation of CD180 on responsive CLL cells leads to activation of
      either prosurvival Bruton tyrosine kinase (BTK)/phosphatidylinositol-4,5
      bisphosphate 3-kinase (PI3K)/AKT-mediated, or proapoptotic p38 mitogen-activated
      protein kinase (p38MAPK)-mediated signaling pathways, while selective
      immunoglobulin M (sIgM) ligation predominantly engages the BTK/PI3K/AKT pathway.
      Furthermore, pretreatment of CLL cells with anti-CD180 redirects IgM-mediated
      signaling from the prosurvival BTK/PI3K/AKT toward the proapoptotic p38MAPK
      pathway. Thus preengaging CD180 could prevent further prosurvival signaling
      mediated via the BCR and, instead, induce CLL cell apoptosis, opening the door to
      therapeutic profiling and new strategies for the treatment of a substantial
      cohort of CLL patients.

PMID- 25611437
TI  - Building technology services that address student needs.
AB  - A 16-question technology use survey was conducted to assess incoming health
      sciences students' knowledge of and interest in current technologies, and to
      identify student device and tool preferences. Survey questions were developed by
      colleagues at a peer institution and then edited to match this library's student
      population. Two years of student responses have been compiled, compared, and
      reviewed as a means for informing library decisions related to technology and
      resource purchases. Instruction and event programming have been revised to meet
      student preferences. Based on the number of students using Apple products,
      librarians are addressing the need to become more proficient with this platform. 

PMID- 25611436
TI  - Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of
      three Eastern Asian populations.
AB  - OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non
      Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide.
      The first large-scale genome-wide association study (GWAS) of DLBCL with over
      4000 cases conducted among individuals of European ancestry recently identified
      five independent SNPs that achieved genome-wide significance, and two SNPs that
      showed a suggestive association with DLBCL risk. METHODS: To evaluate whether
      Eastern Asians and individuals of European ancestry share similar genetic risk
      factors for this disease, we attempted to replicate these GWAS findings in a
      pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea,
      and Thailand. RESULTS: Three of the five genome-wide significant SNPs from the
      DLBCL GWAS were significantly associated with DLBCL in our study population,
      including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome
      wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend =
      3.9 * 10(-10)). Additionally, we observed a significant association with PVT1
      rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 * 10(-6)),
      which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per
      allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). CONCLUSIONS: Our study,
      which provides the first evaluation in Eastern Asians of SNPs definitively
      associated with DLBCL risk in individuals of European ancestry, indicates that at
      least some of the genetic factors associated with risk of DLBCL are similar
      between these populations.

PMID- 25611438
TI  - RELM: developing a serious game to teach evidence-based medicine in an academic
      health sciences setting.
AB  - Gaming as a means of delivering online education continues to gain in popularity.
      Online games provide an engaging and enjoyable way of learning. Gaming is
      especially appropriate for case-based teaching, and provides a conducive
      environment for adult independent learning. With funding from the National
      Network of Libraries of Medicine, Pacific Northwest Region (NN/LM PNR), the
      University of Washington (UW) Health Sciences Library, and the UW School of
      Medicine are collaborating to create an interactive, self-paced online game that
      teaches players to employ the steps in practicing evidence-based medicine. The
      game encourages life-long learning and literacy skills and could be used for
      providing continuing medical education. 

PMID- 25611439
TI  - Analysis of a librarian-mediated literature search service.
AB  - Librarian-mediated literature searching is a key service provided at medical
      libraries. This analysis outlines ten years of data on 19,248 literature searches
      and describes information on the volume and frequency of search requests, time
      spent per search, databases used, and professional designations of the patron
      requestors. Combined with information on best practices for expert searching and
      evaluations of similar services, these findings were used to form recommendations
      on the improvement and standardization of a literature search service at a large
      health library system. 

PMID- 25611441
TI  - Disability search tips and resources.
AB  - Demographic projections for people living in the United States indicate a growing
      need for information on disabilities. This article discusses a limited number of
      concepts in disability, along with relevant thesaurus terms and suggested search
      techniques in four databases: PubMed, CINAHL, REHABDATA, and the Center for
      International Rehabilitation Research Information and Exchange's (CIRRIE)
      Database of International Research. The article closes with annotations of
      potentially useful websites that focus on concerns of persons with disabilities,
      their caregivers, and researchers in disability. 

PMID- 25611440
TI  - Starting a research data management program based in a university library.
AB  - As the need for research data management grows, many libraries are considering
      adding data services to help with the research mission of their institution. The
      Virginia Commonwealth University (VCU) Libraries created a position and hired a
      director of research data management in September 2013. The position was new to
      the libraries and the university. With the backing of the library administration,
      a plan for building relationships with VCU faculty, researchers, students,
      service and resource providers, including grant administrators, was developed to
      educate and engage the community in data management plan writing and research
      data management training. 

PMID- 25611442
TI  - Development and examination of a rubric for evaluating point-of-care medical
      applications for mobile devices.
AB  - The rapid development and updates of mobile medical resource applications (apps)
      highlight the need for an evaluation tool to assess the content of these
      resources. The purpose of the study was to develop and test a new evaluation
      rubric for medical resource apps. The evaluation rubric was designed using
      existing literature and through a collaborative effort between a hospital and an
      academic librarian. Testing found scores ranging from 23% to 88% for the apps.
      The evaluation rubric proved able to distinguish levels of quality within each
      content component of the apps, demonstrating potential for standardization of
      medical resource app evaluations. 

PMID- 25611443
TI  - JoVE: the Journal of Visualized Experiments.
AB  - The Journal of Visualized Experiments (JoVE) is the world's first scientific
      video journal and is designed to communicate research and scientific methods in
      an innovative, intuitive way. JoVE includes a wide range of biomedical videos,
      from biology to immunology and bioengineering to clinical and translation
      medicine. This column describes the browsing and searching capabilities of JoVE,
      as well as its additional features (including the JoVE Scientific Education
      Database designed for students in scientific fields). 

PMID- 25611444
TI  - If this then that: an introduction to automated task services.
AB  - This article explores automated task services, a type of website that allows
      users to create rules that are triggered by activity on one website and perform a
      task on another site. The most well-known automated task service is If This Then
      That (IFTTT), but recently a large number of these services have sprung up. These
      services can be used to connect websites, apps, business services, and even
      devices such as phones and home automation equipment. This allows for millions of
      possible combinations of rules, triggers, and actions. Librarians can put these
      services to use in many ways, from automating social media postings to
      remembering to bring their umbrella when rain is in the forecast. A list of
      popular automated task services is included, as well as a number of ideas for
      using these services in libraries. 

PMID- 25611445
TI  - Impressions of an old master: hospital libraries and librarians, 1970-2014.
AB  - This article is a retrospective look at the changes in hospital libraries from
      1970 to 2014 based on the author's experience and a survey of the literature
      related to hospital libraries indexed in PubMed from 1970 to the present. New
      roles for librarians and methods for conveying the value of libraries to
      administrators are described. 

PMID- 25611446
TI  - Closing the loop on nursing library instruction: using student performance to
      improve outcomes.
AB  - Two librarians analyzed nursing students' performance on an information literacy
      assignment to determine how they could change their instruction to better assist
      the students in comprehending the material. After identifying major areas of
      difficulty, including the use of search techniques, they revised both the
      instruction and the assignment, closing the loop by utilizing their assessment
      data. Next, they analyzed those results to evaluate the effectiveness of their
      changes and to make further improvements, thus demonstrating the iterative nature
      of instruction and assessment. The evidence-based instruction cycle of teaching,
      assessing, and revising should be repeated frequently to keep the assignment
      fresh and relevant. 

PMID- 25611451
TI  - Spectral Doppler interrogation of mitral regurgitation -spot diagnosis.
AB  - Mitral regurgitation (MR) is one of the most common valvular lesions that are
      readily identified by transthoracic echocardiography. Color Doppler imaging is
      the modality of choice for the recognition of MR, and it plays an important role
      in the assessment of regurgitation severity. Continuous wave (CW) Doppler is
      commonly used to interrogate the MR signal, and this modality can provide highly
      useful data regarding several physiological and pathological parameters. In this
      manuscript, we present a series of cases that illustrate the various hemodynamic
      parameters that can be derived from analysis of the CW Doppler signal of MR. 

PMID- 25611452
TI  - Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the
      reverse of the Will Rogers phenomenon?
AB  - Downstaging after neoadjuvant treatment is increasingly used as a prognostic
      factor and surrogate endpoint in clinical trials. However, in recent trials of
      neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging
      did not translate into a benefit with regard to either disease-free survival
      (DFS) or overall survival. By analyzing the 10-year outcome data of the German
      CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer
      patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5
      fluorouracil-based chemoradiotherapy. Nevertheless, these patients with
      International Union for Cancer Control stage II disease were found to be at a
      higher risk of developing distant metastases and had poorer DFS compared with
      patients with corresponding TNM tumor (sub)groups in the postoperative treatment
      arm, whereas patients with International Union for Cancer Control stage III
      disease demonstrated a nonsignificant trend toward a worse outcome after
      preoperative treatment. Overall, DFS remained identical in both treatment arms.
      Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of
      the Will Rogers phenomenon and therefore may not be a reliable endpoint for long
      term outcomes.

PMID- 25611453
TI  - Activity of select dehydrogenases with sepharose-immobilized N(6)-carboxymethyl
      NAD.
AB  - N(6)-carboxymethyl-NAD (N(6)-CM-NAD) can be used to immobilize NAD onto a
      substrate containing terminal primary amines. We previously immobilized N(6)-CM
      NAD onto sepharose beads and showed that Thermotoga maritima glycerol
      dehydrogenase could use the immobilized cofactor with cofactor recycling. We now
      show that Saccharomyces cerevisiae alcohol dehydrogenase, rabbit muscle L-lactate
      dehydrogenase (type XI), bovine liver L-glutamic dehydrogenase (type III),
      Leuconostoc mesenteroides glucose-6-phosphate dehydro-genase, and Thermotoga
      maritima mannitol dehydrogenase are active with soluble N(6)-CM-NAD. The products
      of all enzymes but 6-phospho-D-glucono-1,5-lactone were formed when sepharose
      immobilized N(6)-CM-NAD was recycled by T. maritima glycerol dehydrogenase,
      indicating that N(6)-immobilized NAD is suitable for use by a variety of
      different dehydrogenases. Observations of the enzyme active sites suggest that
      steric hindrance plays a greater role in limiting or allowing activity with the
      modified cofactor than do polarity and charge of the residues surrounding the
      N(6)-amine group on NAD. 

PMID- 25611454
TI  - Stress-Related Functional Connectivity Changes Between Auditory Cortex and
      Cingulate in Tinnitus.
AB  - The question arises whether functional connectivity (FC) changes between the
      distress and tinnitus loudness network during resting state depends on the amount
      of distress tinnitus patients' experience. Fifty-five patients with constant
      chronic tinnitus were included in this study. Electroencephalography (EEG)
      recordings were performed and seed-based (at the auditory cortex) source
      localized FC (lagged phase synchronization) was computed for the different EEG
      frequency bands. Results initially demonstrate that the correlation between
      loudness and distress is nonlinear. Loudness correlates with beta3 and gamma band
      activity in the auditory cortices, and distress with alpha1 and beta3 changes in
      the subgenual, dorsal anterior, and posterior cingulate cortex. In comparison to
      nontinnitus controls, seed-based FC differed between the left auditory cortices
      for the alpha1 and beta3 bands in a network encompassing the posterior cingulate
      cortex extending into the parahippocampal area, the anterior cingulate, and
      insula. Furthermore, distress changes the FC between the auditory cortex,
      encoding loudness, and different parts of the cingulate, encoding distress: the
      subgenual anterior, the dorsal anterior, and the posterior cingulate. These
      changes are specific for the alpha1 and beta3 frequency bands. These results fit
      with a recently proposed model that states that tinnitus is generated by multiple
      dynamically active separable but overlapping networks, each characterizing a
      specific aspect of the unified tinnitus percept, but adds to this concept that
      the interaction between these networks is a complex interplay of correlations and
      anti-correlations between areas involved in distress and loudness depending on
      the distress state of the tinnitus patient. 

PMID- 25611455
TI  - Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion
      Immediate-Release Suvorexant Tablets and Application to Clinically Relevant
      Dissolution Specifications and In-Process Controls.
AB  - Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified
      release products, there are limited reports of successful IVIVCs for immediate
      release (IR) formulations. This manuscript details the development of a Multiple
      Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS
      class II compound, and its application to establishing dissolution specifications
      and in-process controls. Four different 40 mg batches were manufactured at
      different tablet hardnesses to produce distinct dissolution profiles. These
      batches were evaluated in a relative bioavailability clinical study in healthy
      volunteers. Although no differences were observed for the total exposure (AUC) of
      the different batches, a clear relationship between dissolution and Cmax was
      observed. A validated Multiple Level C IVIVC against Cmax was developed for the
      10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration
      time. The relationship established between tablet tensile strength and
      dissolution was subsequently used to inform suitable tablet hardness ranges
      within acceptable Cmax limits. This is the first published report for a validated
      Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how
      this approach can facilitate Quality by Design in formulation development and
      help toward clinically relevant specifications and in-process controls.

PMID- 25611456
TI  - Cytomorphology of sebaceous carcinoma with analysis of p40 antibody expression.
AB  - BACKGROUND: Sebaceous carcinomas (SBCs) are aggressive tumors with the potential
      to cause great morbidity and mortality. Poorly-differentiated tumors may at times
      pose challenges for the correct diagnosis. p40, a new antibody that targets a
      short isoform of p63 has been shown as a promising squamous cell marker. In this
      study, we sought to evaluate cytomorphological features of SBC and p40 expression
      analysis. METHODS: A total of 29 previously diagnosed cases of SBCs including
      fine-needle aspirates and histopathology specimens from various sites were
      reviewed and studied for p40 expression. p40 nuclear expression was semi
      quantitatively assessed. Adequate positive and negative controls of non-small
      cell lung carcinoma were taken for comparison. Expression pattern of normal
      sebaceous glands was also analyzed. RESULTS: Of the 29 cases, 13 (44.8%) were
      from the periocular region. The most common extraocular site was parotid gland.
      Morphologically tumors were categorized into well- and poorly-differentiated
      varieties based on extent of sebaceous differentiation. p40 positivity was seen
      in all cases of cytology aspirates and histology sections with similar intensity.
      No difference in percentage positivity of cells was recorded in well- and poorly
      differentiated tumors. CONCLUSION: p40 can be a valuable marker when evaluating
      tumors with possible sebaceous differentiation. Although p40 expression in SBCs
      is not as useful for the differential diagnosis that includes poorly
      differentiated squamous cell carcinoma, this study, for the first time in the
      literature, highlights an important observation that p40 can be utilized as a
      marker for sebaceous lineage.

PMID- 25611457
TI  - Micelle-enhanced spectrofluorimetric determination of amlexanox in bioadhesive
      buccal tablets: application to content uniformity testing.
AB  - A highly sensitive, simple and rapid spectrofluorimetric method was developed for
      the determination of Amlexanox (AMX) in its bioadhesive buccal tablets. The
      proposed method is based on measuring the native fluorescence of the methanolic
      solution of AMX at 400 nm after excitation at 242 nm in 0.2 M borate buffer (pH
      10) and 0.5% w/v sodium dodecyl sulfate (SDS) solution. The interaction of AMX
      with SDS was studied, and the enhanced fluorescence intensity was exploited to
      develop an assay method for the determination of AMX. The relative fluorescence
      intensity-concentration plot was rectilinear over the range 5.0-80.0 ng/mL, with
      a lower detection limit of 0.57 ng/mL and a lower quantification limit of 1.74
      ng/mL. The proposed method was successfully applied to the analysis of AMX in its
      commercial tablets. Moreover, content uniformity testing was conducted by
      applying official USP guidelines. Statistical evaluation and comparison of the
      data obtained using the proposed and comparison methods revealed good accuracy
      and precision for the proposed method.

PMID- 25611458
TI  - Grit and perseverance in suicidal behavior and non-suicidal self-injury.
AB  - Data indicate persistence facilitates suicidal behavior. Non-suicidal self-injury
      (NSSI) is characterized by difficulty persisting while upset. The relationship
      between NSSI and suicidal behavior thus may hinge upon persistence. Participants
      were 604 undergraduates (79.5% women; 42.4% African American; 6.1% with 1 + prior
      suicide attempt). Data were collected online via self-report and analyzed using
      hierarchical multiple regression. As expected, higher levels of grit and
      perseverance predicted more frequent suicide attempts. Furthermore, grit and
      perseverance moderated the relationship between NSSI and suicide attempts, which
      increased in magnitude as individuals reported greater persistence. Findings
      depict suicidal behavior as a deliberate pursuit of death. 

PMID- 25611459
TI  - Five new cases of breast cancer in transsexual persons.
AB  - Cross-sex hormone treatment of transsexual people may be associated with the
      induction and growth stimulation of hormone-related malignancies. We report here
      five cases of breast cancer, three in female-to-male (FtoM) transsexual subjects
      and two in male-to-female (MtoF) transsexual subjects. In the general population
      the incidence of breast cancer increases with age and with duration of exposure
      to sex hormones. This pattern was not recognised in these five transsexual
      subjects. Tumours occurred at a relatively young age (respectively, 48, 41, 41,
      52 and 46 years old) and mostly after a relatively short span of time of cross
      sex hormone treatment (9, 9-10 but in one after 30 years). Occurrence of breast
      cancer was rare. As has been reported earlier, breast tumours may occur in
      residual mammary tissue after breast ablation in FtoM transsexual people. For
      adequate treatment and decisions on further cross-sex hormone treatment it is
      important to have information on the staging and histology of the breast tumour
      (type, grade and receptor status), with an upcoming role for the androgen
      receptor status, especially in FtoM transsexual subjects with breast cancer who
      receive testosterone administration. This information should be taken into
      account when considering further cross-sex hormone treatment.

PMID- 25611460
TI  - Host association drives genetic divergence in the bed bug, Cimex lectularius.
AB  - Genetic differentiation may exist among sympatric populations of a species due to
      long-term associations with alternative hosts (i.e. host-associated
      differentiation). While host-associated differentiation has been documented in
      several phytophagus insects, there are far fewer cases known in animal parasites.
      The bed bug, Cimex lectularius, a wingless insect, represents a potential model
      organism for elucidating the processes involved in host-associated
      differentiation in animal parasites with relatively limited mobility. In
      conjunction with the expansion of modern humans from Africa into Eurasia, it has
      been speculated that bed bugs extended their host range from bats to humans in
      their shared cave domiciles throughout Eurasia. C. lectularius that associate
      with humans have a cosmopolitan distribution, whereas those associated with bats
      occur across Europe, often in human-built structures. We assessed genetic
      structure and gene flow within and among populations collected in association
      with each host using mtDNA, microsatellite loci and knock-down resistance gene
      variants. Both nuclear and mitochondrial data support a lack of significant
      contemporary gene flow between host-specific populations. Within locations human
      associated bed bug populations exhibit limited genetic diversity and elevated
      levels of inbreeding, likely due to human-mediated movement, infrequent
      additional introduction events per infestation, and pest control. In contrast,
      populations within bat roosts exhibit higher genetic diversity and lower levels
      of relatedness, suggesting populations are stable with temporal fluctuations due
      to host dispersal and bug mortality. In concert with previously published
      evidence of morphological and behavioural differentiation, the genetic data
      presented here suggest C. lectularius is currently undergoing lineage divergence
      through host association. 

PMID- 25611461
TI  - 3D and 2D structural characterization of 1D Al/Al2 O3 biphasic nanostructures.
AB  - 1D Al/Al2 O3 nanostructures have been synthesized by chemical vapour deposition
      (CVD) of the molecular precursor [(t) BuOAlH2 ]2 . The deposited nanostructures
      grow chaotically on the substrate forming a layer with a high porosity (80%).
      Depending on the deposition time, diverse nanostructured surfaces with different
      distribution densities were achieved. A three-dimensional (3D) reconstruction has
      been evaluated for every nanostructure density using the Focus Ion Beam (FIB)
      tomography technique and reconstruction software tools. Several structural
      parameters such as porosity, Euler number, geometrical tortuosity and aspect
      ratio have been quantified through the analysis with specified software of the
      reconstructions. Additionally roughness of the prepared surfaces has been
      characterized at micro- and nanoscale using profilometry and AFM techniques,
      respectively. While high aspects ratio around 20-30 indicates a strong anisotropy
      in the structure, high porosity values (around 80%) is observed as a consequence
      of highly tangled geometry of such 1D nanostructures. 

PMID- 25611462
TI  - A nonhomogeneous hidden markov model for gene mapping based on next-generation
      sequencing data.
AB  - The analysis of polygenetic characteristics for mapping quantitative trait loci
      (QTL) remains an important challenge. QTL analysis requires two or more strains
      of organisms that differ substantially in the (poly-)genetic trait of interest,
      resulting in a heterozygous offspring. The offspring with the trait of interest
      is selected and subsequently screened for molecular markers such as single
      nucleotide polymorphisms (SNPs) with next-generation sequencing. Gene mapping
      relies on the co-segregation between genes and/or markers. Genes and/or markers
      that are linked to a QTL influencing the trait will segregate more frequently
      with this locus. For each identified marker, observed mismatch frequencies
      between the reads of the offspring and the parental reference strains can be
      modeled by a multinomial distribution with the probabilities depending on the
      state of an underlying, unobserved Markov process. The states indicate whether
      the SNP is located in a (vicinity of a) QTL or not. Consequently, genomic loci
      associated with the QTL can be discovered by analyzing hidden states along the
      genome. The aforementioned hidden Markov model assumes that the identified SNPs
      are equally distributed along the chromosome and does not take the distance
      between neighboring SNPs into account. The distance between the neighboring SNPs
      could influence the chance of co-segregation between genes and markers. To
      address this issue, we propose a nonhomogeneous hidden Markov model with a
      transition matrix that depends on a set of distance-varying observed covariates.
      The application of the model is illustrated on the data from a study of ethanol
      tolerance in yeast. 

PMID- 25611463
TI  - Maintenance of intracellular hypoxia and adequate heat shock response are
      essential requirements for pathogenicity and virulence of Entamoeba histolytica.
AB  - Adhesion to cells, cytotoxicity and proteolysis are functions required for
      virulence and pathogenicity of Entamoeba histolytica. However, there was no
      correlation between these in vitro functions and the early elimination of non
      pathogenic E. dispar and non-virulent E. histolytica (nvEh) in experimental
      amoebic liver abscesses developed in hamsters. Thus, additional functions may be
      involved in amoebic pathogenicity and virulence. In the present study, an
      integral experimental assessment, including innovative technologies for analyses
      of amoebal pathophysiology, cell biology, biochemistry and transcriptomics, was
      carried out to elucidate whether other cellular processes are involved in amoebal
      pathogenicity and virulence. In comparison with virulent E. histolytica, the data
      indicated that the main reasons for the early clearance of nvEh from hamster
      liver are decreased intracellular H2 O2 detoxification rate and deficient heat
      shock protein expression, whereas for E. dispar, it is a relatively lower
      capacity for O2 reduction. Therefore, maintenance of an intracellular hypoxic
      environment combined with the induction of an adequate parasite response to
      oxidative stress are essential requirements for Entamoeba survival in the liver,
      and therefore for pathogenicity.

PMID- 25611464
TI  - A novel nanocomposite hydrogel with precisely tunable UCST and LCST.
AB  - Novel thermosensitive nanocomposite (NC) hydrogels consisting of
      organic/inorganic networks are prepared via in situ free radical polymerization
      of 2-(2-methoxyethoxy) ethyl methacrylate (MEO2 MA) and oligo(ethylene glycol)
      methacrylate (OEGMA) in the presence of inorganic cross-linker clay in aqueous
      solution. The obtained clay/P(MEO2 MA-co-OEGMA) hydrogels exhibit double volume
      phase transition temperatures, an upper critical solution temperature (UCST), and
      a lower critical solution temperature (LCST), which can be controlled between 5
      and 85  degrees C by varying the fraction of OEGMA units and the weight
      percentage of cross-linker clay. These new types of NC hydrogels with excellent
      reversible thermosensitivity are promising for temperature-sensitive applications
      such as smart optical switches. 

PMID- 25611465
TI  - Trends in overweight and obesity in soldiers entering the US Army, 1989-2012.
AB  - OBJECTIVE: The US Army recruits new soldiers from an increasingly obese civilian
      population. The change in weight status at entry into the Army between 1989 and
      2012 and the demographic characteristics associated with overweight/obesity at
      entry were examined. METHODS: 1,741,070 unique individuals with complete sex,
      age, and anthropometric information contributed data to linear and logistic
      regressions examining time trends and associations between demographic
      characteristics and overweight/obesity. RESULTS: The prevalence of overweight
      (body mass index 25-<30 kg/m(2)) generally increased, from 25.8% (1989) to 37.2%
      (2012), peaking at 37.9% (2011). The prevalence of obesity (body mass index >=30
      kg/m(2)) also increased from 5.6% (1989) to 8.0% (2012), peaking at 12.3% (2009);
      2005-2009 annual prevalence exceeded 10%. The most consistent demographic
      characteristics predicting overweight/obesity were male sex, older age, Hispanic
      or Asian/Pacific Island race/ethnicity, and being married. There were no distinct
      geographic trends. CONCLUSIONS: The US Army is not immune to the US obesity
      epidemic. Demographic characteristics associated with being overweight or obese
      should be considered when developing military-sponsored weight management
      programs for new soldiers.

PMID- 25611467
TI  - 'Human bocavirus in Pakistani children with gastroenteritis'.
AB  - Human Bocaviruses (HBoV) have been detected in human respiratory and
      gastrointestinal infections worldwide. Four genotypes of HBoV (HBoV1-4) have been
      described; HBoV-1 is associated with respiratory tract infections while HBoV-2, 
      3, and -4 genotypes are considered as entero-pathogenic although the exact role
      largely remains unclear. The global prevalence of HBoV has been reported, but the
      epidemiological data from Pakistan is largely unavailable to date. This study was
      conducted to understand the genetic diversity and disease prevalence of HBoV in
      hospitalized Pakistani children with acute diarrhea. During 2009, a total of 365
      stool samples were collected from children hospitalized with gastrointestinal
      symptoms (as per WHO case definitions) at Rawalpindi General Hospital, Pakistan.
      Demographic and clinical data were recorded using a standardized questionnaire.
      The samples were tested for HBoV and rotavirus using real-time RT-PCR and ELISA,
      respectively. There were 47 (13%) samples positive for HBoV with 98% (n = 46)
      showing co-infection with rotavirus. HBoV-1 was the most frequently detected and
      was found in 94% samples followed by HBoV-2 and HBoV-3 genotypes. The mean age of
      infected children was 7.57 +/- 5.4 months while detection was more frequent in
      males (n = 32, 68%). All cases recovered after 2.43 +/- 1.0 mean days of
      treatment. On phylogenetic analysis, HBoV strains from Pakistan clustered closely
      with viruses from neighboring Bangladesh and China. These findings represent the
      first known epidemiological study in Pakistan to investigate the role of HBoV in
      acute gastroenteritis. The clinical data demonstrates that HBoV is not
      significantly associated with gastroenteritis alone and predominantly co
      infections with rotavirus are found.

PMID- 25611466
TI  - Variability in tuberculosis granuloma T cell responses exists, but a balance of
      pro- and anti-inflammatory cytokines is associated with sterilization.
AB  - Lung granulomas are the pathologic hallmark of tuberculosis (TB). T cells are a
      major cellular component of TB lung granulomas and are known to play an important
      role in containment of Mycobacterium tuberculosis (Mtb) infection. We used
      cynomolgus macaques, a non-human primate model that recapitulates human TB with
      clinically active disease, latent infection or early infection, to understand
      functional characteristics and dynamics of T cells in individual granulomas. We
      sought to correlate T cell cytokine response and bacterial burden of each
      granuloma, as well as granuloma and systemic responses in individual animals. Our
      results support that each granuloma within an individual host is independent with
      respect to total cell numbers, proportion of T cells, pattern of cytokine
      response, and bacterial burden. The spectrum of these components overlaps greatly
      amongst animals with different clinical status, indicating that a diversity of
      granulomas exists within an individual host. On average only about 8% of T cells
      from granulomas respond with cytokine production after stimulation with Mtb
      specific antigens, and few "multi-functional" T cells were observed. However,
      granulomas were found to be "multi-functional" with respect to the combinations
      of functional T cells that were identified among lesions from individual animals.
      Although the responses generally overlapped, sterile granulomas had modestly
      higher frequencies of T cells making IL-17, TNF and any of T-1 (IFN-gamma, IL-2,
      or TNF) and/or T-17 (IL-17) cytokines than non-sterile granulomas. An inverse
      correlation was observed between bacterial burden with TNF and T-1/T-17 responses
      in individual granulomas, and a combinatorial analysis of pair-wise cytokine
      responses indicated that granulomas with T cells producing both pro- and anti
      inflammatory cytokines (e.g. IL-10 and IL-17) were associated with clearance of
      Mtb. Preliminary evaluation suggests that systemic responses in the blood do not
      accurately reflect local T cell responses within granulomas. 

PMID- 25611468
TI  - Burr hole washout versus craniotomy for chronic subdural hematoma: patient
      outcome and cost analysis.
AB  - Chronic subdural hematomas (CSDH), which are frequently encountered in
      neurosurgical practice, are, in the majority of cases, ideally treated with
      surgical drainage. Despite this common practice, there is still controversy
      surrounding the best surgical procedure. With lack of clear evidence of a
      superior technique, surgeons are free to base the decision on other factors that
      are not related to patient care. A retrospective chart review of 119 patients
      requiring surgical drainage of CSDH was conducted at a large tertiary care center
      over a three-year period. Of the cases reviewed, 58 patients underwent
      craniotomy, while 61 patients underwent burr hole washout. The study focused on
      re-operation rates, mortality, and morbidity, as measured by Glasgow coma scores
      (GCS), discharge Rankin disability scores, and discharge disposition. Secondary
      endpoints included length of stay and cost of procedure. Burr hole washout was
      superior to craniotomy with respect to patient outcome, length of stay and
      recurrence rates. In both study groups, patients required additional surgical
      procedures (6.6% of burr hole patients and 24.1% of craniotomy patients) (P =
      0.0156). Of the patients treated with craniotomy, 51.7% were discharged home,
      whereas 65.6% of the burr hole patients were discharged home. Patients who
      underwent burr hole washout spent a mean of 78.8 minutes in the operating suite
      while the patients undergoing craniotomy spent 129.4 minutes (P < 0.001). The
      difference in mean cost per patient, based solely on operating time, was $2,828
      (P < 0.001). This does not include the further cost due to additional procedures
      and hospital stay. The mean length of stay after surgical intervention was 3 days
      longer for the craniotomy group (P = 0.0465). Based on this retrospective study,
      burr hole washout is superior for both patients' clinical and financial outcome;
      however, prospective long-term multicenter clinical studies are required to
      verify these findings. 

PMID- 25611469
TI  - Caution on corticosteroids for preterm delivery: learning from missteps.

PMID- 25611470
TI  - It's not Ebola ... it's the systems.

PMID- 25611471
TI  - Breaking new ground in family planning communication.

PMID- 25611472
TI  - A better future for injectable contraception?

PMID- 25611473
TI  - The future of routine immunization in the developing world: challenges and
      opportunities.

PMID- 25611474
TI  - Strategies to reduce risks in ARV supply chains in the developing world.

PMID- 25611475
TI  - A stewardship approach to shaping the future of public health supply chain
      systems.

PMID- 25611476
TI  - Demand generation activities and modern contraceptive use in urban areas of four
      countries: a longitudinal evaluation.
AB  - Family planning is crucial for preventing unintended pregnancies and for
      improving maternal and child health and well-being. In urban areas where there
      are large inequities in family planning use, particularly among the urban poor,
      programs are needed to increase access to and use of contraception among those
      most in need. This paper presents the midterm evaluation findings of the Urban
      Reproductive Health Initiative (Urban RH Initiative) programs, funded by the Bill
      & Melinda Gates Foundation, that are being implemented in 4 countries: India
      (Uttar Pradesh), Kenya, Nigeria, and Senegal. Between 2010 and 2013, the
      Measurement, Learning & Evaluation (MLE) project collected baseline and 2-year
      longitudinal follow-up data from women in target study cities to examine the role
      of demand generation activities undertaken as part of the Urban RH Initiative
      programs. Evaluation results demonstrate that, in each country where it was
      measured, outreach by community health or family planning workers as well as
      local radio programs were significantly associated with increased use of modern
      contraceptive methods. In addition, in India and Nigeria, television programs had
      a significant effect on modern contraceptive use, and in Kenya and Nigeria, the
      program slogans and materials that were blanketed across the cities (eg,
      leaflets/brochures distributed at health clinics and the program logo placed on
      all forms of materials, from market umbrellas to health facility signs and
      television programs) were also significantly associated with modern method use.
      Our results show that targeted, multilevel demand generation activities can make
      an important contribution to increasing modern contraceptive use in urban areas
      and could impact Millennium Development Goals for improved maternal and child
      health and access to reproductive health for all. 

PMID- 25611478
TI  - Strengthening government management capacity to scale up HIV prevention programs
      through the use of Technical Support Units: lessons from Karnataka state, India.
AB  - Scaling up HIV prevention programming among key populations (female sex workers
      and men who have sex with men) has been a central strategy of the Government of
      India. However, state governments have lacked the technical and managerial
      capacity to oversee and scale up interventions or to absorb donor-funded
      programs. In response, the national government contracted Technical Support Units
      (TSUs), teams with expertise from the private and nongovernmental sectors, to
      collaborate with and assist state governments. In 2008, a TSU was established in
      Karnataka, one of 6 Indian states with the highest HIV prevalence in the country
      and where monitoring showed that its prevention programs were reaching only 5% of
      key populations. The TSU provided support to the state in 5 key areas: assisting
      in strategic planning, rolling out a comprehensive monitoring and evaluation
      system, providing supportive supervision to intervention units, facilitating
      training, and assisting with information, education, and communication
      activities. This collaborative management model helped to increase capacity of
      the state, enabling it to take over funding and oversight of HIV prevention
      programs previously funded through donors. With the combined efforts of the TSU
      and the state government, the number of intervention units statewide increased
      from 40 to 126 between 2009 and 2013. Monthly contacts with female sex workers
      increased from 5% in 2008 to 88% in 2012, and with men who have sex with men,
      from 36% in 2009 to 81% in 2012. There were also increases in the proportion of
      both populations who visited HIV testing and counseling centers (from 3% to 47%
      among female sex workers and from 6% to 33% among men who have sex with men) and
      sexually transmitted infection clinics (from 4% to 75% among female sex workers
      and from 7% to 67% among men who have sex with men). Changes in sexual behaviors
      among key populations were also documented. For example, between 2008 and 2010,
      the proportion of surveyed female sex workers in 9 districts reporting that they
      used a condom at last intercourse rose from 60% to 68%; in 6 districts, the
      proportion of surveyed men who have sex with men reporting that they used a
      condom at last anal sex increased from 89% to 97%. The Karnataka experience
      suggests that TSUs can help governments enhance managerial and technical
      resources and leverage funds more effectively. With careful management of the
      working and reporting relationships between the TSU and the state government,
      this additional capacity can pave the way for the government to improve and scale
      up programs and to absorb previously donor-funded programs. 

PMID- 25611477
TI  - Using behavior change communication to lead a comprehensive family planning
      program: the Nigerian Urban Reproductive Health Initiative.
AB  - BACKGROUND: The Nigerian Urban Reproductive Health Initiative (NURHI), a 6-year
      comprehensive family planning program (2009-2015) in 4 cities, intentionally
      applies communication theories to all program elements, not just the demand
      generation ones, relying mainly on a theory called ideation-the concept that
      contraceptive use is influenced by people's beliefs, ideas, and feelings and that
      changing these ideational factors can change people's behavior. PROGRAM
      DESCRIPTION: The project used multiple communication channels to foster dialogue
      about family planning, increase social approval for it, and improve accurate
      knowledge about contraceptives. Mobile service delivery was started in the third
      year to improve access to clinical methods in slums. METHODS: Data from
      representative baseline (2010-11) and midterm (2012) surveys of women of
      reproductive age in the project cities were analyzed. We also used propensity
      score matching to create a statistically equivalent control group of women not
      exposed to project activities, and we examined service delivery data from NURHI
      supported clinics (January 2011-May 2013) to determine the contribution of mobile
      services to total family planning services. RESULTS: Three years into the
      initiative, analysis of longitudinal data shows that use of modern contraceptives
      has increased in each city, varying from 2.3 to 15.5 percentage points, and that
      the observed increases were predicted by exposure to NURHI activities. Of note is
      that modern method use increased substantially among the poorest wealth quintiles
      in project cities, on average, by 8.4 percentage points. The more project
      activities women were exposed to, the greater their contraceptive use. For
      example, among women not using a modern method at baseline, contraceptive
      prevalence among those with no exposure by midterm was 19.1% vs. 43.4% among
      those with high exposure. Project exposure had a positive dose-response
      relationship with ideation, as did ideation and contraceptive use. By the end of
      the observation period, mobile services were contributing nearly 50% of total
      family planning services provided through NURHI-supported clinics. Propensity
      score matching found that the increase in contraceptive use in the 4 cities
      attributable to project exposure was 9.9 percentage points. Intention to use
      family planning in the next 12 months also increased by 7.5 to 10.2 percentage
      points across the 4 cities. CONCLUSION: Demand-led family planning programs, in
      which demand generation is the driving force behind the design rather than the
      conventional, service delivery-oriented approach, may be more suitable in places
      where expressed demand for contraceptives is low.

PMID- 25611480
TI  - Getting closer to people: family planning provision by drug shops in Uganda.
AB  - BACKGROUND: Private-sector drug shops are often the first point of health care in
      sub-Saharan Africa. Training and supporting drug shop and pharmacy staff to
      provide a wide range of contraceptive methods and information is a promising high
      impact practice for which more information is needed to fully document
      implementation experience and impact. METHODS: Between September 2010 and March
      2011, we trained 139 drug shop operators (DSOs) in 4 districts of Uganda to
      safely administer intramuscular DMPA (depot medroxyprogesterone acetate)
      contraceptive injections. In 2012, we approached 54 of these DSOs and interviewed
      a convenience sample of 585 of their family planning clients to assess clients'
      contraceptive use and perspectives on the quality of care and satisfaction with
      services. Finally, we compared service statistics from April to June 2011 from
      drug shops, community health workers (CHWs), and government clinics in 3
      districts to determine the drug shop market share of family planning services.
      RESULTS: Most drug shop family planning clients interviewed were women with low
      socioeconomic status. The large majority (89%) were continuing family planning
      users. DMPA was the preferred contraceptive. Almost half of the drug shop clients
      had switched from other providers, primarily from government health clinics,
      mostly as a result of more convenient locations, shorter waiting times, and fewer
      stock-outs in drug shops. All clients reported that the DSOs treated them
      respectfully, and 93% trusted the drug shop operator to maintain privacy. Three
      quarters felt that drug shops offered affordable family planning services. Most
      of the DMPA clients (74%) were very satisfied with receiving their method from
      the drug shop and 98% intended to get the next injection from the drug shop.
      Between April and June 2011, clinics, CHWs, and drug shops in 3 districts
      delivered equivalent proportions of couple-years of protection, with drug shops
      leading marginally at 36%, followed by clinics (33%) and CHWs (31%). CONCLUSION:
      Drug shops can be a viable and convenient source of short-acting contraceptive
      methods, including DMPA, serving as a complement to government services. Family
      planning programs in Uganda and elsewhere should consider including drug shops in
      the network of community-based family planning providers.

PMID- 25611479
TI  - Policy and programmatic considerations for introducing a longer-acting injectable
      contraceptive: perspectives of stakeholders from Kenya and Rwanda.
AB  - BACKGROUND: More than 40 million women use injectable contraceptives to prevent
      pregnancy, and most current or previous injectable users report being satisfied
      with the method. However, while women may find injectables acceptable, they may
      not always find them accessible due to stock-outs and difficulties with returning
      to the clinic for reinjections. FHI 360 is spearheading efforts to develop a
      longer-acting injectable (LAI) contraceptive that could provide at least 6 months
      of protection against pregnancy. This article addresses systems-level
      considerations for the introduction of a new LAI. METHODS: We conducted
      qualitative case studies in Kenya and Rwanda-two countries that have high levels
      of injectable use but with different service delivery contexts. Between June and
      September 2012, we conducted in-depth interviews with 27 service providers and 19
      policy makers and program implementers focusing on 4 themes: systems-level
      barriers and facilitators to delivering LAI services; process for introducing an
      LAI; LAI distribution approaches; and potential LAI characteristics. We also
      obtained electronic feedback from 28 international family planning opinion
      leaders. RESULTS: Respondents indicated strong interest in an LAI and thought it
      would appeal to existing injectable users as well as new family planning clients,
      both for spacing and for limiting births. Providers appreciated the potential for
      a lighter workload due to fewer follow-up visits, but they were concerned that
      fewer visits would also decrease their ability to help women manage side effects.
      The providers also appreciated the 1-month grace period for follow-up LAI
      injections; some seemed unaware of the latest international guidance that had
      increased the grace period from 2 weeks to 4 weeks for the currently available 3
      month injectable. The majority of policy makers and program implementers were
      supportive of letting community health workers provide the method, but many
      nurses and midwives in Kenya had reservations about the approach. At the policy
      level, respondents indicated that obtaining regulatory approvals before
      introducing the new method could be costly and time-consuming. Manufacturing and
      procurement decisions could also affect cost and availability. CONCLUSIONS:
      Successful introduction of a potential longer-acting injectable may be enhanced
      by considering broader systemic issues, including managing cost to the health
      system and users, expanding access through community-based distribution, and
      training providers on the latest service delivery guidelines.

PMID- 25611482
TI  - Courage is not the absence of fear: responding to the Ebola outbreak in Liberia.

PMID- 25611481
TI  - Maternal mental health in Amhara region, Ethiopia: a cross-sectional survey.
AB  - BACKGROUND: Postpartum common mental disorders (CMD) such as depression and
      anxiety are increasingly recognized for their burden in low-resource countries
      such as Ethiopia. However, the magnitude of postpartum CMD in Ethiopia is not
      well-established. This short report describes the mental health status of women
      who had given birth in the last 24 months in the Amhara region of Ethiopia.
      METHODS: A cross-sectional survey was conducted among 1,319 women aged 15-49
      years old who had a delivery in the previous 24 months from 30 randomly selected
      kebeles (smallest administrative unit in Ethiopia) across Amhara region. The
      survey included the Self-Reporting Questionnaire (SRQ-20) developed by the World
      Health Organization-a CMD screening instrument that includes 20 yes/no questions
      on depression, anxiety, and somatic symptoms experienced in the last 30 days. We
      used 2 cutoff scores to determine probable cases of mental disorder: (1) 4/5 (<=
      4 "yes" responses=non-case, >= 5 "yes" responses=case) based on a study that
      validated the SRQ-20 against a diagnostic tool in Butajira, Ethiopia, and (2) a
      more conservative and commonly used 7/8 cutoff. RESULTS: Among the 1,294 women
      who completed the full survey including the SRQ-20, 32.8% had probable CMD using
      the 4/5 cutoff score versus 19.8% using the more conservative 7/8 cutoff. About
      15% of the women responded affirmatively that they had had suicidal thoughts.
      CONCLUSION: Poor mental health was common among the surveyed women who had given
      birth in the past 24 months in Amhara region, Ethiopia. Integrating mental health
      care into maternal and child health services could potentially alleviate the
      burden of CMD among women in the extended postpartum period.

PMID- 25611483
TI  - Spatial-temporal variation and primary ecological drivers of Anopheles sinensis
      human biting rates in malaria epidemic-prone regions of China.
AB  - BACKGROUND: Robust malaria vector surveillance is essential for optimally
      selecting and targeting vector control measures. Sixty-two vector surveillance
      sites were established between 2005 and 2008 by the national malaria surveillance
      program in China to measure Anopheles sinensis human biting rates. Using these
      data to determine the primary ecological drivers of malaria vector human biting
      rates in malaria epidemic-prone regions of China will allow better targeting of
      vector control resources in space and time as the country aims to eliminate
      malaria. METHODS: We analyzed data from 62 malaria surveillance sentinel sites
      from 2005 to 2008. Linear mixed effects models were used to identify the primary
      ecological drivers for Anopheles sinensis human biting rates as well as to
      explore the spatial-temporal variation of relevant factors at surveillance sites
      throughout China. RESULTS: Minimum semimonthly temperature (beta = 2.99; 95%
      confidence interval (CI) 2.07- 3.92), enhanced vegetation index (beta =1.07; 95%
      CI 0.11-2.03), and paddy index (the percentage of rice paddy field in the total
      cultivated land area of each site) (beta = 0.86; 95% CI 0.17-1.56) were
      associated with greater An. Sinensis human biting rates, while increasing
      distance to the nearest river was associated with lower An. Sinensis human biting
      rates (beta = -1.47; 95% CI -2.88, -0.06). The temporal variation (sigma(s0)(2) =
      0.83) in biting rates was much larger than the spatial variation (sigma(t)(2) =
      1.35), with 19.3% of temporal variation attributable to differences in minimum
      temperature and enhanced vegetation index and 16.9% of spatial variance due to
      distance to the nearest river and the paddy index. DISCUSSION: Substantial
      spatial-temporal variation in An. Sinensis human biting rates exists in malaria
      epidemic-prone regions of China, with minimum temperature and enhanced vegetation
      index accounting for the greatest proportion of temporal variation and distance
      to nearest river and paddy index accounting for the greatest proportion of
      spatial variation amongst observed ecological drivers. CONCLUSIONS: Targeted
      vector control measures based on these findings can support the ongoing malaria
      elimination efforts in China more effectively.

PMID- 25611485
TI  - A rapid and sensitive LC-MS/MS method for quantification of 3,29-dibenzoyl
      rarounitriol in rat plasma: application to a pharmacokinetic study.
AB  - A rapid, sensitive and high-throughput liquid chromatography-tandem mass
      spectrometry was established and validated to assay the concentrations of 3,29
      dibenzoyl rarounitriol in rat plasma. Plasma samples were processed by liquid
      liquid extraction with ethyl acetate and separated on a Hypersil Gold C18 column
      (50 * 4.6 mm, 3 um) at an isocratic flow rate of 0.5 mL/min using methanol-10 mm
      ammonium acetate-formic acid (90:10:0.1, v/v/v) as mobile phase. The total run
      time was 5 min for each sample. MS/MS detection was accomplished in selected
      reaction monitoring mode with positive electrospray ionization. The calibration
      curve was linear over the concentration range of 0.125-50 ng/mL with lower limit
      of quantification of 0.125 ng/mL. The intra- and inter-day precisions were <10.1%
      in terms of coefficient of variation, and the accuracy was within +/-11.7% in
      terms of relative error. The developed method was successfully applied to a
      pharmacokinetic study of 3,29-dibenzoyl rarounitriol following intragastric
      administration of 3.65 mg/kg to Wistar rats.

PMID- 25611486
TI  - 5-Sulfosalicylic acid dihydrate-based pretreatment for the modification of enzyme
      linked immunoassay of fluoroquinolones in fishery products.
AB  - A simple, rapid sample extraction method for the determination of FQs was
      developed. Fishery samples were extracted with 2% of 5-sulfosalicylic acid
      dihydrate and the extracts were analyzed directly without any further
      purification or clean-up procedures. The FQs were determined with standards of 2%
      of 5-sulfosalicylic acid dihydrate in the concentration range of 0.1-25.6 MUg L(
      1), and the limit of detection (LOD) was 0.1 MUg L(-1). The matrix interference
      originated from fishery samples was eliminated by 2% of 5-sulfosalicylic acid
      dihydrate and did not interact with horseradish peroxidase (HRP) labeled IgG in
      western blotting. No significant matrix interference was observed as samples
      extracted with 2% of 5-sulfosalicylic acid dihydrate. Recoveries of FQs in
      fishery muscle were between 72.37-94.35% in the concentrations range of 10-50 MUg
      kg(-1).This extraction procedure was much rapider and simpler to conventional
      ELISA extraction procedure and could be used as a time-saving and cost-effective
      method for FQs monitoring in fishery samples. 

PMID- 25611484
TI  - The effect of antenatal depression and selective serotonin reuptake inhibitor
      treatment on nerve growth factor signaling in human placenta.
AB  - Depressive symptoms during pregnancy are common and may have impact on the
      developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most
      prescribed antidepressant treatment, but unfortunately, these treatments can also
      negatively affect the behavioral development and health of a child during
      pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus
      far not fully known effects in the offspring. The neurotrophic growth factor
      (NGF) is involved in neuronal cell survival and differentiation, and altered
      placenta levels have been found to increase the risk for pregnancy complications,
      similar to those found in women treated with SSRIs. We therefore investigated
      whether the NGF signaling pathway was altered in the placenta from women treated
      with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and
      healthy mothers (n = 12). Results from immunohistochemical stainings revealed
      that placental NGF protein levels of SSRI-treated women were increased in both
      trophoblasts and endothelial cells compared with depressed and control women. In
      addition, downstream of the NGF receptor TrkA, increased levels of the signaling
      proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a
      tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells
      in SSRI-treated women when compared to healthy controls. SSRI-treated women also
      displayed increased levels of phosphorylated ROCK2 in all placental cell types
      studied in comparison with depressed and control women. Interestingly, in
      placental endothelial cells from depressed women, NGF levels were significantly
      lower compared to control women, but ROCK2 levels were increased compared with
      control and SSRI-treated women. Taken together, these results show that the NGF
      signaling and downstream pathways in the placenta are affected by SSRI treatment
      and/or antenatal depression. This might lead to an altered placental function,
      although the clinical relevance of our findings still needs to be investigated. 

PMID- 25611487
TI  - In vivo visualization and ex vivo quantification of murine breast cancer cells in
      the mouse brain using MRI cell tracking and electron paramagnetic resonance.
AB  - Cell tracking could be useful to elucidate fundamental processes of cancer
      biology such as metastasis. The aim of this study was to visualize, using MRI,
      and to quantify, using electron paramagnetic resonance (EPR), the entrapment of
      murine breast cancer cells labeled with superparamagnetic iron oxide particles
      (SPIOs) in the mouse brain after intracardiac injection. For this purpose,
      luciferase-expressing murine 4 T1-luc breast cancer cells were labeled with
      fluorescent Molday ION Rhodamine B SPIOs. Following intracardiac injection, SPIO
      labeled 4 T1-luc cells were imaged using multiple gradient-echo sequences. Ex
      vivo iron oxide quantification in the mouse brain was performed using EPR (9
      GHz). The long-term fate of 4 T1-luc cells after injection was characterized
      using bioluminescence imaging (BLI), brain MRI and immunofluorescence. We
      observed hypointense spots due to SPIO-labeled cells in the mouse brain 4 h after
      injection on T2 *-weighted images. Histology studies showed that SPIO-labeled
      cancer cells were localized within blood vessels shortly after delivery. Ex vivo
      quantification of SPIOs showed that less than 1% of the injected cells were taken
      up by the mouse brain after injection. MRI experiments did not reveal the
      development of macrometastases in the mouse brain several days after injection,
      but immunofluorescence studies demonstrated that these cells found in the brain
      established micrometastases. Concerning the metastatic patterns of 4 T1-luc
      cells, an EPR biodistribution study demonstrated that SPIO-labeled 4 T1-luc cells
      were also entrapped in the lungs of mice after intracardiac injection. BLI
      performed 6 days after injection of 4 T1-luc cells showed that this cell line
      formed macrometastases in the lungs and in the bones. Conclusively, EPR and MRI
      were found to be complementary for cell tracking applications. MRI cell tracking
      at 11.7 T allowed sensitive detection of isolated SPIO-labeled cells in the mouse
      brain, whereas EPR allowed the assessment of the number of SPIO-labeled cells in
      organs shortly after injection.

PMID- 25611488
TI  - Calcium and phosphate release from resin-based materials containing different
      calcium orthophosphate nanoparticles.
AB  - The study compared ion release from resin-based materials containing calcium
      orthophosphates. Amorphous calcium phosphate (ACP), dicalcium phosphate anhydrous
      (DCPA), dicalcium phosphate dihydrate (DCPD), and tricalcium phosphate (beta-TCP)
      nanoparticles were characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM), dynamic light scattering (DLS), and surface area
      (nitrogen adsorption isotherms, BET method). Nanoparticles were added to a
      dimethacrylate-based resin and materials were tested for degree of conversion
      (DC) and calcium/phosphate release up to 28 days under pH 5.5 and 7.0. Data were
      analyzed by ANOVA/Tukey test (alpha: 0.05).The crystallinity of DCPA, DCPD, and
      beta-TCP were confirmed, as well as the ACP amorphous nature. DCPD and beta-TCP
      presented larger agglomerates than DCPA and ACP. The surface area of ACP was 5-11
      times higher than those of the other nanoparticles. Materials showed similar DC.
      The material containing ACP released significantly more ions than the others,
      which released similar amounts of calcium and, in most cases, phosphate. Ion
      release was not affected by pH. Calcium release decreased between 7 and 21 days,
      while phosphate levels remained constant after 14 days. In conclusion, ACP higher
      ion release can be ascribed to its high surface area. DCPA, DCPD, and beta-TCP
      had similar performances as ion-releasing fillers.

PMID- 25611489
TI  - Alternating copolymerization of propylene oxide with biorenewable terpene-based
      cyclic anhydrides: a sustainable route to aliphatic polyesters with high glass
      transition temperatures.
AB  - The alternating copolymerization of propylene oxide with terpene-based cyclic
      anhydrides catalyzed by chromium, cobalt, and aluminum salen complexes is
      reported. The use of the Diels-Alder adduct of alpha-terpinene and maleic
      anhydride as the cyclic anhydride comonomer results in amorphous polyesters that
      exhibit glass transition temperatures (Tg ) of up to 109  degrees C. The
      polymerization conditions and choice of catalyst have a dramatic impact on the
      molecular weight distribution, the relative stereochemistry of the diester units
      along the polymer chain, and ultimately the Tg of the resulting polymer. The
      aluminum salen complex exhibits exceptional selectivity for copolymerization
      without transesterification or epimerization side reactions. The resulting
      polyesters are highly alternating and have high molecular weights and narrow
      polydispersities. 

PMID- 25611490
TI  - Evaluation of the olfactory bulb volume and olfactory threshold in patients with
      nasal polyps and impact of functional endoscopic sinus surgery: a longitudinal
      study.
AB  - BACKGROUND: Debate still persists on the relation between olfactory bulb volume
      (OBV) and olfactory function. Many studies suggest that olfactory deprivation
      decreases the OBV. The aim of this study was to compare the olfactory threshold
      and OBV of patients with nasal polyps to healthy individuals and to evaluate the
      impact of functional endoscopic sinus surgery (FESS) on OBV and olfactory
      threshold. METHODS: A longitudinal study was carried out in Tehran between 2011
      and 2012. Twenty-two patients with nasal polyps were compared with 37 healthy
      individuals. Olfactory threshold test and magnetic resonance imaging (MRI) were
      performed on all participants. Twenty-two patients in case group were followed
      for 6 months after FESS. OBV and olfactory threshold were measured after 6
      months. RESULTS: There was no significant difference between the age, gender, and
      OBV of the 2 groups. However, the difference between olfactory threshold was
      significant (p = 0.005). The olfactory threshold showed no significant relation
      with OBV (p > 0.05). The correlation between Lund-Mackay score and the mean total
      OBV and left OBV was significant (r = -0.15, p = 0.045; r = -0.22, p = 0.047;
      respectively). The decrease in olfactory threshold measured after FESS was
      statistically significant. Right, left, and total OBV significantly increased
      after FESS. CONCLUSION: The results of our study show that FESS has a significant
      impact on OBV increment and olfactory threshold decrement. The olfactory bulb is
      a plastic structure and improvement in peripheral olfactory function results in
      increase in OBV. However, further studies are mandated, in order to establish
      this result.

PMID- 25611491
TI  - Classification of CEBPA mutated acute myeloid leukemia by GATA2 mutations.

PMID- 25611493
TI  - Shoulder-muscle electromyography during shoulder external-rotation exercises with
      and without slight abduction.
AB  - CONTEXT: Standing and side-lying external-rotation exercises produce high
      activation of the deltoid and infraspinatus. Slight shoulder abduction during
      these exercises may decrease deltoid activity and increase infraspinatus
      activity. OBJECTIVE: To determine if the addition of a towel under the arm during
      standing and side-lying external rotation affects infraspinatus, middle and
      posterior deltoid, and pectoralis major activation characteristics compared with
      a no-towel condition. DESIGN: Controlled laboratory study. PARTICIPANTS: 20 male
      volunteers (age 26 +/- 3 y, height 1.80 +/- 0.07 m, mass 77 +/- 10 kg) who were
      right-hand dominant and had bilaterally healthy shoulders with no current
      cervical pathology and no skin infection or shoulder lesion. INTERVENTIONS:
      External-rotation exercises without a towel roll (0 degrees  shoulder abduction)
      and with a towel roll (30 degrees  shoulder abduction) were performed in a
      standing and side-lying. MAIN OUTCOME MEASURES: Maximal voluntary isometric
      contraction for the infraspinatus, middle and posterior deltoid, and pectoralis
      major and external rotation in standing and side-lying with and without a towel
      roll were performed. Normalized average and peak surface EMG amplitude were
      compared between the towel conditions during standing and side-lying external
      rotation. RESULTS: Both infraspinatus and pectoralis major activity had no
      significant differences between the towel conditions in standing and side-lying
      (P > .05). In standing and side-lying, posterior-deltoid activity was
      significantly greater with a towel roll (P < .05). Middle-deltoid activity had no
      significant differences between the towel conditions in standing (P > .05).
      However, in side-lying, middle-deltoid activity was significantly lower with a
      towel roll (P < .05). CONCLUSION: Middle-deltoid activity decreased with a towel
      roll during side-lying exercises. More data are needed to determine if a towel
      roll could be used to potentially reduce superior glide during external-rotation
      exercises.

PMID- 25611492
TI  - Factors that influence the generation of autobiographical memory conjunction
      errors.
AB  - The constructive nature of memory is generally adaptive, allowing us to
      efficiently store, process and learn from life events, and simulate future
      scenarios to prepare ourselves for what may come. However, the cost of a flexibly
      constructive memory system is the occasional conjunction error, whereby the
      components of an event are authentic, but the combination of those components is
      false. Using a novel recombination paradigm, it was demonstrated that details
      from one autobiographical memory (AM) may be incorrectly incorporated into
      another, forming AM conjunction errors that elude typical reality monitoring
      checks. The factors that contribute to the creation of these conjunction errors
      were examined across two experiments. Conjunction errors were more likely to
      occur when the corresponding details were partially rather than fully recombined,
      likely due to increased plausibility and ease of simulation of partially
      recombined scenarios. Brief periods of imagination increased conjunction error
      rates, in line with the imagination inflation effect. Subjective ratings suggest
      that this inflation is due to similarity of phenomenological experience between
      conjunction and authentic memories, consistent with a source monitoring
      perspective. Moreover, objective scoring of memory content indicates that
      increased perceptual detail may be particularly important for the formation of AM
      conjunction errors. 

PMID- 25611494
TI  - A proposed framework for consensus-based lung tumour volume auto-segmentation in
      4D computed tomography imaging.
AB  - This work aims to propose and validate a framework for tumour volume auto
      segmentation based on ground-truth estimates derived from multi-physician input
      contours to expedite 4D-CT based lung tumour volume delineation. 4D-CT datasets
      of ten non-small cell lung cancer (NSCLC) patients were manually segmented by 6
      physicians. Multi-expert ground truth (GT) estimates were constructed using the
      STAPLE algorithm for the gross tumour volume (GTV) on all respiratory phases.
      Next, using a deformable model-based method, multi-expert GT on each individual
      phase of the 4D-CT dataset was propagated to all other phases providing auto
      segmented GTVs and motion encompassing internal gross target volumes (IGTVs)
      based on GT estimates (STAPLE) from each respiratory phase of the 4D-CT dataset.
      Accuracy assessment of auto-segmentation employed graph cuts for 3D-shape
      reconstruction and point-set registration-based analysis yielding volumetric and
      distance-based measures. STAPLE-based auto-segmented GTV accuracy ranged from
      (81.51  +/-  1.92) to (97.27  +/-  0.28)% volumetric overlap of the estimated
      ground truth. IGTV auto-segmentation showed significantly improved accuracies
      with reduced variance for all patients ranging from 90.87 to 98.57% volumetric
      overlap of the ground truth volume. Additional metrics supported these
      observations with statistical significance. Accuracy of auto-segmentation was
      shown to be largely independent of selection of the initial propagation phase.
      IGTV construction based on auto-segmented GTVs within the 4D-CT dataset provided
      accurate and reliable target volumes compared to manual segmentation-based GT
      estimates. While inter-/intra-observer effects were largely mitigated, the
      proposed segmentation workflow is more complex than that of current clinical
      practice and requires further development.

PMID- 25611495
TI  - [Editorial].

PMID- 25611496
TI  - [Post-surgical management of split-thickness skin grafts in oculoplastic
      surgery].
AB  - Malignant skin tumours in periocular regions often demand ophthalmo-surgical
      measures. Split-thickness skin grafts still represent an important treatment
      alternative when plastic-reconstructive covering through local tissue of the
      facial area is impossible. Essential technical steps to gain viable split
      thickness skin grafts are introduced. Current standards in the after-treatment of
      split-thickness skin grafts at the receiving location as well as in the after
      care of the donor area are presented from interdisciplinary points of view
      referring to the latest publications. Hydrocolloidal dressings are recommended
      for the after-treatment of removal areas such as the inside of the forearm since
      they improve post-surgical management for the ophthalmologist significantly and
      help in abbreviating healing duration. Pain sensation of the patient as well as
      the rate of infection are minimal. Throughout the early stages, split-thickness
      skin grafts at reception areas often demand an intensified local massage
      treatment with hydrocortisone 2.5 % ophthalmic cream. During the later stages
      follow-up measures should be stopped neither too soon nor abruptly. Ointments
      with polysiloxane and silicon dioxide preserve skin suppleness and prevent the
      occurrence of shrinkage as well as hypertrophic scars. 

PMID- 25611498
TI  - [Botulinum toxin injections for senile entropium].
AB  - Involutive changes in the collagen and muscular structures of the lower lid in
      ageing may lead to the formation of senile entropium. Treatment of this condition
      may be achieved using botulinum toxin injections to the dislocated orbicularis
      muscle. These injections lead to cessation of the symptoms for a mean of 3.8
      months. Repeat injections are possible. Botulinum toxin injections are a viable
      option for patients who are not amenable to surgical correction of the entropium.

PMID- 25611497
TI  - [Lateral canthopexy - a simple addition to lower lid blepharoplasty].
AB  - Rejuvination of the lower lid is a challenging procedure. Lower lid malposition
      and ectropion are serious postoperative complications. Therefore presurgical
      assessment of the lower lid function and laxity are a must before performing a
      blepharoplasty. Lateral canthopexy is an effective procedure to minimise the risk
      of postsurgical ectropion. Its necessity increases with rising age of the
      patients. The canthopexy supports the lower lid postion in the case of increasing
      vertical tension. 

PMID- 25611499
TI  - [Post enucleation socket syndrome - new and established surgical solutions].
AB  - The orbital volume after enucleation or evisceration might shrink over time due
      to atrophy of the orbital fat and connective tissue. This can lead to prosthesis
      misfit and an unsatisfactory cosmetic result. This so-called post enucleation
      socket syndrome (PESS) needs a secondary orbital volume augmentation. The
      techniques for orbital volume augmentation are secondary orbital implants or
      implant exchange, orbital floor implants or injectable augmentation. The surgical
      possibilities are described and discussed with special attention to indications
      and chances. 

PMID- 25611500
TI  - [Minimally invasive lacrimal duct surgery with a multimodal concept for
      functional lacrimal stenosis].
AB  - PURPOSE: The aim of this study was to evaluate the long-term success rates of a
      multimodal concept for treating functional nasolacrimal duct obstruction (FNLDO)
      consisting of minimally invasive lacrimal duct surgery and additional treatment
      of the conjunctiva, the puncta or the lids if necessary. METHODS: Clinical
      outcomes and subjective symptoms of 118 consecutive patients with the main
      diagnosis FNLDO were studied in a retrospective design. RESULTS: Of the 118 cases
      64 % were treated by microendoscopy and microdrill only while 36 % needed
      additional treatments. In 76 % of all cases (82 % in the group of patients who
      were treated by microdrill only) the patients reported their symptoms to have
      "improved" after a median follow-up of 14 months. Up to the age of 70 years more
      women were affected by FNLDO, while it was more common among male patients above
      this age. In older patients additional treatment especially tightening of the
      lids was required more frequently. CONCLUSION: Transcanalicular microendoscopy of
      the lacrimal duct alone or in combination with additional treatments, if needed,
      showed satisfactory long-term outcomes in patients suffering from FNLDO and can
      be considered a valuable and minimally invasive option for these patients.

PMID- 25611501
TI  - [Guideline of the Professional Association of German Ophthalmologists eV and the
      German Ophthalmology Society:. Guideline No. 24a:. Uveitis intermedia (July
      2014)].

PMID- 25611503
TI  - Dangerous leaks: blood-brain barrier woes in the aging hippocampus.
AB  - A leaky blood-brain barrier has long been implicated in cognitive dysfunction in
      aging and neurodegeneration, but reliable human data were lacking. Here, Montagne
      et al. (2015) provide the first in vivo evidence of blood-brain barrier
      disruption in the aging hippocampus and in minimal cognitive impairment.

PMID- 25611502
TI  - Bugs, guts, and glia: how microbiota influence enteric gliogenesis and migration.
AB  - Enteric glia are neural crest derivatives. Kabouridis et al. (2015) now show in
      adult animals that new glia arise within the ganglia of enteric plexuses and then
      migrate centripetally to colonize the mucosa. Remarkably, enteric microbiota
      regulate this critical migration.

PMID- 25611504
TI  - Striking the right balance: cortical modulation of the subthalamic nucleus-globus
      pallidus circuit.
AB  - The subthalamic nucleus-globus pallidus network is a potential source of
      oscillations in Parkinson's disease, but the mechanism is unknown. In this issue
      of Neuron, Chu et al. (2015) present a cortically driven form of heterosynaptic
      plasticity that could promote oscillatory activity after dopamine depletion.

PMID- 25611505
TI  - Beta and gamma rhythms go with the flow.
AB  - Information flows through visual areas in opposite directions during "bottom-up"
      intake of current stimuli and "top-down" processes such as attention or memory.
      In this issue of Neuron, Bastos et al. (2015) report that rhythms of different
      frequencies coordinate bottom-up and top-down information streams.

PMID- 25611506
TI  - Subcellular localization of K+ channels in mammalian brain neurons: remarkable
      precision in the midst of extraordinary complexity.
AB  - Potassium channels (KChs) are the most diverse ion channels, in part due to
      extensive combinatorial assembly of a large number of principal and auxiliary
      subunits into an assortment of KCh complexes. Their structural and functional
      diversity allows KChs to play diverse roles in neuronal function. Localization of
      KChs within specialized neuronal compartments defines their physiological role
      and also fundamentally impacts their activity, due to localized exposure to
      diverse cellular determinants of channel function. Recent studies in mammalian
      brain reveal an exquisite refinement of KCh subcellular localization. This
      includes axonal KChs at the initial segment, and near/within nodes of Ranvier and
      presynaptic terminals, dendritic KChs found at sites reflecting specific synaptic
      input, and KChs defining novel neuronal compartments. Painting the remarkable
      diversity of KChs onto the complex architecture of mammalian neurons creates an
      elegant picture of electrical signal processing underlying the sophisticated
      function of individual neuronal compartments, and ultimately neurotransmission
      and behavior. 

PMID- 25611509
TI  - Anterograde C1ql1 signaling is required in order to determine and maintain a
      single-winner climbing fiber in the mouse cerebellum.
AB  - Neuronal networks are dynamically modified by selective synapse pruning during
      development and adulthood. However, how certain connections win the competition
      with others and are subsequently maintained is not fully understood. Here, we
      show that C1ql1, a member of the C1q family of proteins, is provided by climbing
      fibers (CFs) and serves as a crucial anterograde signal to determine and maintain
      the single-winner CF in the mouse cerebellum throughout development and
      adulthood. C1ql1 specifically binds to the brain-specific angiogenesis inhibitor
      3 (Bai3), which is a member of the cell-adhesion G-protein-coupled receptor
      family and expressed on postsynaptic Purkinje cells. C1ql1-Bai3 signaling is
      required for motor learning but not for gross motor performance or coordination.
      Because related family members of C1ql1 and Bai3 are expressed in various brain
      regions, the mechanism described here likely applies to synapse formation,
      maintenance, and function in multiple neuronal circuits essential for important
      brain functions.

PMID- 25611508
TI  - Blood-brain barrier breakdown in the aging human hippocampus.
AB  - The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens,
      and cells into the brain that is essential for normal neuronal functioning and
      information processing. Post-mortem tissue analysis indicates BBB damage in
      Alzheimer's disease (AD). The timing of BBB breakdown remains, however, elusive.
      Using an advanced dynamic contrast-enhanced MRI protocol with high spatial and
      temporal resolutions to quantify regional BBB permeability in the living human
      brain, we show an age-dependent BBB breakdown in the hippocampus, a region
      critical for learning and memory that is affected early in AD. The BBB breakdown
      in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild
      cognitive impairment that correlated with injury to BBB-associated pericytes, as
      shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is
      an early event in the aging human brain that begins in the hippocampus and may
      contribute to cognitive impairment. VIDEO ABSTRACT: 

PMID- 25611507
TI  - The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
AB  - Understanding the function of genes mutated in hereditary forms of Parkinson's
      disease yields insight into disease etiology and reveals new pathways in cell
      biology. Although mutations or variants in many genes increase the susceptibility
      to Parkinson's disease, only a handful of monogenic causes of parkinsonism have
      been identified. Biochemical and genetic studies reveal that the products of two
      genes that are mutated in autosomal recessive parkinsonism, PINK1 and Parkin,
      normally work together in the same pathway to govern mitochondrial quality
      control, bolstering previous evidence that mitochondrial damage is involved in
      Parkinson's disease. PINK1 accumulates on the outer membrane of damaged
      mitochondria, activates Parkin's E3 ubiquitin ligase activity, and recruits
      Parkin to the dysfunctional mitochondrion. Then, Parkin ubiquitinates outer
      mitochondrial membrane proteins to trigger selective autophagy. This review
      covers the normal functions that PINK1 and Parkin play within cells, their
      molecular mechanisms of action, and the pathophysiological consequences of their
      loss. 

PMID- 25611511
TI  - The stabilized supralinear network: a unifying circuit motif underlying multi
      input integration in sensory cortex.
AB  - Neurons in sensory cortex integrate multiple influences to parse objects and
      support perception. Across multiple cortical areas, integration is characterized
      by two neuronal response properties: (1) surround suppression--modulatory
      contextual stimuli suppress responses to driving stimuli; and (2) "normalization"
      -responses to multiple driving stimuli add sublinearly. These depend on input
      strength: for weak driving stimuli, contextual influences facilitate or more
      weakly suppress and summation becomes linear or supralinear. Understanding the
      circuit operations underlying integration is critical to understanding cortical
      function and disease. We present a simple, general theory. A wealth of
      integrative properties, including the above, emerge robustly from four cortical
      circuit properties: (1) supralinear neuronal input/output functions; (2)
      sufficiently strong recurrent excitation; (3) feedback inhibition; and (4) simple
      spatial properties of intracortical connections. Integrative properties emerge
      dynamically as circuit properties, with excitatory and inhibitory neurons showing
      similar behaviors. In new recordings in visual cortex, we confirm key model
      predictions.

PMID- 25611510
TI  - Genome-wide functional analysis of CREB/long-term memory-dependent transcription
      reveals distinct basal and memory gene expression programs.
AB  - Induced CREB activity is a hallmark of long-term memory, but the full repertoire
      of CREB transcriptional targets required specifically for memory is not known in
      any system. To obtain a more complete picture of the mechanisms involved in
      memory, we combined memory training with genome-wide transcriptional analysis of
      C. elegans CREB mutants. This approach identified 757 significant CREB/memory
      induced targets and confirmed the involvement of known memory genes from other
      organisms, but also suggested new mechanisms and novel components that may be
      conserved through mammals. CREB mediates distinct basal and memory
      transcriptional programs at least partially through spatial restriction of CREB
      activity: basal targets are regulated primarily in nonneuronal tissues, while
      memory targets are enriched for neuronal expression, emanating from CREB activity
      in AIM neurons. This suite of novel memory-associated genes will provide a
      platform for the discovery of orthologous mammalian long-term memory components.

PMID- 25611513
TI  - Diversity of transgenic mouse models for selective targeting of midbrain dopamine
      neurons.
AB  - Ventral tegmental area (VTA) dopamine (DA) neurons have been implicated in
      reward, aversion, salience, cognition, and several neuropsychiatric disorders.
      Optogenetic approaches involving transgenic Cre-driver mouse lines provide
      powerful tools for dissecting DA-specific functions. However, the emerging
      complexity of VTA circuits requires Cre-driver mouse lines that restrict
      transgene expression to a precisely defined cell population. Because of recent
      work reporting that VTA DA neurons projecting to the lateral habenula release
      GABA, but not DA, we performed an extensive anatomical, molecular, and functional
      characterization of prominent DA transgenic mouse driver lines. We find that
      transgenes under control of the tyrosine hydroxylase, but not the dopamine
      transporter, promoter exhibit dramatic non-DA cell-specific expression patterns
      within and around VTA nuclei. Our results demonstrate how Cre expression in
      unintentionally targeted cells in transgenic mouse lines can confound the
      interpretation of supposedly cell-type-specific experiments. This Matters Arising
      paper is in response to Stamatakis et al. (2013), published in Neuron. See also
      the Matters Arising Response paper by Stuber et al. (2015), published
      concurrently with this Matters Arising in Neuron.

PMID- 25611515
TI  - Titanium nanostructures for biomedical applications.
AB  - Titanium and titanium alloys exhibit a unique combination of strength and
      biocompatibility, which enables their use in medical applications and accounts
      for their extensive use as implant materials in the last 50 years. Currently, a
      large amount of research is being carried out in order to determine the optimal
      surface topography for use in bioapplications, and thus the emphasis is on
      nanotechnology for biomedical applications. It was recently shown that titanium
      implants with rough surface topography and free energy increase osteoblast
      adhesion, maturation and subsequent bone formation. Furthermore, the adhesion of
      different cell lines to the surface of titanium implants is influenced by the
      surface characteristics of titanium; namely topography, charge distribution and
      chemistry. The present review article focuses on the specific nanotopography of
      titanium, i.e. titanium dioxide (TiO2) nanotubes, using a simple electrochemical
      anodisation method of the metallic substrate and other processes such as the
      hydrothermal or sol-gel template. One key advantage of using TiO2 nanotubes in
      cell interactions is based on the fact that TiO2 nanotube morphology is
      correlated with cell adhesion, spreading, growth and differentiation of
      mesenchymal stem cells, which were shown to be maximally induced on smaller
      diameter nanotubes (15 nm), but hindered on larger diameter (100 nm) tubes,
      leading to cell death and apoptosis. Research has supported the significance of
      nanotopography (TiO2 nanotube diameter) in cell adhesion and cell growth, and
      suggests that the mechanics of focal adhesion formation are similar among
      different cell types. As such, the present review will focus on perhaps the most
      spectacular and surprising one-dimensional structures and their unique biomedical
      applications for increased osseointegration, protein interaction and
      antibacterial properties. 

PMID- 25611516
TI  - The evolution of reproductive isolation in the Drosophila yakuba complex of
      species.
AB  - In the Drosophila melanogaster subgroup, the yakuba species complex, D. yakuba,
      D. santomea and D. teissieri have identical mitochondrial genomes in spite of
      nuclear differentiation. The first two species can be readily hybridized in the
      laboratory and produce fertile females and sterile males. They also form hybrids
      in natural conditions. Nonetheless, the third species, D. teissieri, was thought
      to be unable to produce hybrids with either D. yakuba or D. santomea. This in
      turn posed the conundrum of why the three species shared a single mitochondrial
      genome. In this report, we show that D. teissieri can indeed hybridize with both
      D. yakuba and D. santomea. The resulting female hybrids from both crosses are
      fertile, whereas the hybrid males are sterile. We also characterize six isolating
      mechanisms that might be involved in keeping the three species apart. Our results
      open the possibility of studying the history of introgression in the yakuba
      species complex and dissecting the genetic basis of interspecific differences
      between these three species by genetic mapping. 

PMID- 25611514
TI  - Considerations when using cre-driver rodent lines for studying ventral tegmental
      area circuitry.
AB  - The use of Cre-driver rodent lines for targeting ventral tegmental area (VTA)
      cell types has generated important and novel insights into how precise
      neurocircuits regulate physiology and behavior. While this approach generally
      results in enhanced cellular specificity, an important issue has recently emerged
      related to the selectivity and penetrance of viral targeting of VTA neurons using
      several Cre-driver transgenic mouse lines. Here, we highlight several
      considerations when utilizing these tools to study the function of genetically
      defined neurocircuits. While VTA dopaminergic neurons have previously been
      targeted and defined by the expression of single genes important for aspects of
      dopamine neurotransmission, many VTA and neighboring cells display dynamic gene
      expression phenotypes that are partially consistent with both classically
      described dopaminergic and non-dopaminergic neurons. Thus, in addition to varying
      degrees of selectivity and penetrance, distinct Cre lines likely permit targeting
      of partially overlapping, but not identical VTA cell populations. This Matters
      Arising Response paper addresses the Lammel et al. (2015) Matters Arising paper,
      published concurrently in Neuron.

PMID- 25611512
TI  - Learning-induced plasticity in medial prefrontal cortex predicts preference
      malleability.
AB  - Learning induces plasticity in neuronal networks. As neuronal populations
      contribute to multiple representations, we reasoned plasticity in one
      representation might influence others. We used human fMRI repetition suppression
      to show that plasticity induced by learning another individual's values impacts
      upon a value representation for oneself in medial prefrontal cortex (mPFC), a
      plasticity also evident behaviorally in a preference shift. We show this
      plasticity is driven by a striatal "prediction error," signaling the discrepancy
      between the other's choice and a subject's own preferences. Thus, our data
      highlight that mPFC encodes agent-independent representations of subjective
      value, such that prediction errors simultaneously update multiple agents' value
      representations. As the resulting change in representational similarity predicts
      interindividual differences in the malleability of subjective preferences, our
      findings shed mechanistic light on complex human processes such as the powerful
      influence of social interaction on beliefs and preferences.

PMID- 25611517
TI  - Paravascular inner retinal defect associated with high myopia or epiretinal
      membrane.
AB  - IMPORTANCE: Paravascular retinal abnormalities are common in highly myopic eyes.
      However, affected areas may be underestimated, and the pathogenesis and effects
      on retinal function remain unclear. OBJECTIVE: To prospectively investigate the
      characteristics and pathogenesis of paravascular inner retinal defects (PIRDs).
      DESIGN, SETTING, AND PARTICIPANTS: Prospective and observational case series
      (between April 2013 and April 2014) at a referral retinal practice among 28
      patients (41 eyes) with PIRDs. The entire affected retinal area was examined in 4
      quadrants in sequential thin sections using optical coherence tomography. The
      effect of PIRDs on retinal function was examined using Goldmann perimetry. MAIN
      OUTCOMES AND MEASURES: Morphological changes on optical coherence tomography
      sections and visual field test by Goldmann perimetry. RESULTS: On fundus
      photography, PIRDs appeared as spindle-shaped or caterpillar-shaped dark areas
      along the major retinal vessels disconnected from the optic disc. On optical
      coherence tomography cross-sections of retinal vessels, PIRDs often appeared as
      cystoid or fissure-like spaces; however, longitudinal optical coherence
      tomography sections along retinal vessels revealed that most PIRDs were actually
      wide defects in the inner retina or located beneath the major retinal vessels,
      often deviating into the vitreous cavity. Of 41 eyes with PIRDs, 37 (90%) were
      myopic; 21 eyes (51%) had high myopia. The mean refractive error of the eyes with
      PIRDs was -7.94 (95% CI, -9.48 to -6.40) diopters. The mean axial length of the
      eyes with PIRDs was 26.96 (95% CI, 25.42-28.49) mm. Twenty-one eyes (51%) showed
      epiretinal membrane in the macular area. In these eyes, PIRDs had formed along
      the temporal arcade vessels, which increasingly deviated toward the fovea by
      epiretinal membrane traction. Of 41 eyes with PIRDs, 35 showed visual field
      defects corresponding to the PIRD locations. The most common visual field defects
      were relative Bjerrum scotoma (in 75% [60 of 80]; 95% CI, 66%-85%) and nasal
      steps (in 59% [47 of 80]; 95% CI, 48%-70%) corresponding to the PIRD predilection
      locations. CONCLUSIONS AND RELEVANCE: Paravascular inner retinal defects
      primarily occur in eyes with high myopia or epiretinal membrane. Deviated retinal
      vessels due to axial elongation or epiretinal membrane traction may be involved
      in the pathogenesis. Paravascular inner retinal defects often cause retinal
      dysfunction corresponding to the location. A PIRD may partially overlap with
      retinal lesions previously reported as cleavage of the retinal nerve fiber layer,
      inner retinal cleavage, paravascular retinal cysts, or lamellar holes. However,
      the term PIRD more precisely describes the characteristic features of the lesion.

PMID- 25611518
TI  - Experimental and Modeling Study of the Temperature and Pressure Dependence of the
      Reaction C2H5 + O2 (+ M) -> C2H5O2 (+ M).
AB  - The reaction C2H5 + O2 (+ M) -> C2H5O2 (+ M) was studied at 298 K at pressures of
      the bath gas M = Ar between 100 and 1000 bar. The transition from the falloff
      curve of an energy transfer mechanism to a high pressure range with contributions
      from the radical complex mechanism was observed. Further experiments were done
      between 188 and 298 K in the bath gas M = He at pressures in the range 0.7-2.0
      Torr. The available data are analyzed in terms of unimolecular rate theory. An
      improved analytical representation of the temperature and pressure dependence of
      the rate constant is given for conditions where the chemical activation process
      C2H5 + O2 (+ M) -> C2H4 + HO2 (+ M) is only of minor importance. 

PMID- 25611519
TI  - Penicitols A-C and penixanacid A from the mangrove-derived Penicillium
      chrysogenum HDN11-24.
AB  - Three new citrinin analogues, penicitols A-C (1-3), and one new xanthone
      derivative, penixanacid A (4), together with four known biogenetically related
      compounds (5-8), were discovered from the extract of a mangrove-derived fungus,
      Penicillium chrysogenum HND11-24. The structures of penicitols A-C and
      penixanacid A were established through analysis of extensive spectroscopic data.
      Their cytotoxic activity against HeLa, BEL-7402, HEK-293, HCT-116, and A549 cell
      lines was evaluated. 

PMID- 25611521
TI  - Critical thinking about fables: examining language production and comprehension
      in adolescents.
AB  - PURPOSE: This study was designed primarily to determine if a critical-thinking
      task involving fables would elicit greater syntactic complexity than a
      conversational task in adolescents. Another purpose was to determine how well
      adolescents understand critical-thinking questions about fables. METHOD: Forty
      adolescents (N=20 boys and 20 girls; mean age=14 years) with typical language
      development answered critical-thinking questions about the deeper meanings of
      fables. They also participated in a standard conversational task. The syntactic
      complexity of their responses during the speaking tasks was analyzed for mean
      length of communication unit (MLCU) and clausal density (CD). RESULTS: Both
      measures of syntactic complexity, MLCU and CD, were substantially greater during
      the critical-thinking task compared with the conversational task. It was also
      found that the adolescents understood the questions quite well, earning a mean
      accuracy score of 80%. CONCLUSIONS: The critical-thinking task has potential for
      use as a new type of language-sampling tool to examine language production and
      comprehension in adolescents.

PMID- 25611522
TI  - Anesthetic management of a malnourished, 7-year-old child in Malawi undergoing a
      pneumonectomy.
AB  - In this report, we describe the case of a 7-year-old girl presenting to Queen
      Elizabeth Central Hospital, Blantyre, Malawi, with hypoxia and respiratory
      distress. Investigations demonstrated an endobronchial tumor, and she underwent a
      radical left-sided pneumonectomy. This case highlights the challenges of
      anesthesia in a resource-depleted setting. 

PMID- 25611520
TI  - D-serine uptake and release in PC-12 cells measured by chiral microchip
      electrophoresis-mass spectrometry.
AB  - Previous work has established that D-serine (D-Ser) plays important roles in
      certain neurological processes. Study on its uptake/storage and release by
      neuronal cells is highly significant for elucidating relevant mechanisms. In this
      work, PC-12 cells were incubated with racemic Ser (100 MUM each enantiomer).
      After incubation, both intra- and extracellular levels of D-Ser and L-Ser were
      quantified by chiral microchip electrophoresis with mass spectrometric detection.
      It was found the cells preferably took up D-Ser over L-Ser. After 120 min
      incubation, D-Ser percentage ([D-Ser]/([D-Ser] + [L-Ser]) in the culture media
      changed from 50% to 9% while inside the cells it increased from 13% to 67%. Small
      neutral amino acids such as threonine impaired D-Ser uptake. Ser release was
      studied by using PC-12 cells preloaded with D-Ser. KCl, Glu, and Gly evoked Ser
      release. Interestingly, while depolarization by KCl evoked release of Ser as a D
      Ser/L-Ser mixture of 1:1 ratio, the stereoisomeric composition of Ser released
      due to Glu exposure varied with the exposure time, ranging from 73% D-Ser (i.e.,
      [D-Ser] > [L-Ser]) at 2 min to 44% (i.e., [D-Ser] < [L-Ser]) at 14 min, clearly
      indicating a stereochemical preference for D-Ser in Ser release from neuronal
      cells evoked by Glu-receptor activation.

PMID- 25611523
TI  - Editorial comment: anesthetic management of a malnourished, 7-year-old child in
      Malawi undergoing a pneumonectomy.

PMID- 25611524
TI  - Argyria resulting from chronic use of colloidal silver in a patient presenting
      for colonoscopy.
AB  - An elderly male with a history of argyria caused by chronic ingestion of
      colloidal silver presented for elective colonoscopy. The patient's skin was a
      profound blue-gray color that caused concern among staff until his condition was
      identified through his medical and medication history. Colonoscopy and anesthesia
      proceeded without incident. The anesthetic management concerns include
      differentiating argyria from hypoxemia and other pathologies with similar
      appearance and clearly communicating the patient's history of argyria to follow
      on caregivers to prevent unneeded diagnostic or interventional procedures. It is
      also important for caregivers to understand that the altered skin pigmentation of
      argyria does not interfere with pulse oximetry. 

PMID- 25611525
TI  - Cardiac arrest and succinylcholine-induced hyperkalemia in a patient with a
      triton tumor.
AB  - We report a case of succinylcholine-induced hyperkalemia in a patient with a
      mediastinal triton tumor, which is characterized by a rhabdomyosarcomatous
      differentiation. Caution should be taken with succinylcholine use in patients
      presenting with a rhabdomyosarcomatous tumor or with a tumor of unknown cell type
      when histopathological diagnosis is not available. 

PMID- 25611526
TI  - Infraclavicular brachial plexus block for the management of inadvertent
      intraarterial drug administration after arterial insertion of a venous cannula
      during ultrasound-guided venous cannulation.
AB  - This case report documents the inadvertent placement of an arterial cannula
      despite using realtime ultrasound to insert a peripheral venous cannula in a
      child with difficult venous access. The resultant limb ischemia was treated with
      an infraclavicular ultrasound-guided brachial plexus block as sympatholytic
      treatment. 

PMID- 25611527
TI  - Much enhanced catalytic reactivity of cobalt chlorin derivatives on two-electron
      reduction of dioxygen to produce hydrogen peroxide.
AB  - Effects of changes in the redox potential or configuration of cobalt chlorin
      derivatives (Co(II)(Chn) (n = 1-3)) on the catalytic mechanism and the activity
      of two-electron reduction of dioxygen (O2) were investigated based on the
      detailed kinetic study by spectroscopic and electrochemical measurements.
      Nonsubstituted cobalt chlorin complex (Co(II)(Ch1)) efficiently and selectively
      catalyzed two-electron reduction of dioxygen (O2) by a one-electron reductant
      (1,1'-dimethylferrocene) to produce hydrogen peroxide (H2O2) in the presence of
      perchloric acid (HClO4) in benzonitrile (PhCN) at 298 K. The detailed kinetic
      studies have revealed that the rate-determining step in the catalytic cycle is
      the proton-coupled electron transfer reduction of O2 with the protonated
      Co(II)(Ch1) complex ([Co(II)(Ch1H)](+)), where one-electron reduction potential
      of [Co(III)(Ch1)](+) was changed from 0.37 V (vs SCE) to 0.48 V by the addition
      of HClO4 due to the protonation of [Co(III)(Ch1)](+). The introduction of
      electron-withdrawing aldehyde group (position C-3) (Co(II)(Ch3)) and both
      methoxycarbonyl group (position C-13(2)) and aldehyde group (position C-3)
      (Co(II)(Ch2)) on the chlorin ligand resulted in the positive shifts of redox
      potential for Co(III/II) from 0.37 V to 0.45 and 0.40 V, respectively, whereas,
      in the presence of HClO4, no positive shifts of those redox potentials for
      [Co(III)(Chn)](+)/Co(II)(Chn) (n = 2, 3) were observed due to lower acceptability
      of protonation. As a result, such a change in redox property resulted in the
      enhancement of the catalytic reactivity, where the observed rate constant (kobs)
      value of Co(II)(Ch3) was 36-fold larger than that of Co(II)(Ch1). 

PMID- 25611529
TI  - Tetra-phosphonate calix[4]pyrrole cavitands as multitopic receptors for the
      recognition of ion pairs.
AB  - The synthesis, structural characterization, and binding properties of two
      unprecedented multitopic receptors for ion-pair recognition are described. We
      isolated two of the six possible diastereomeric deep cavitand receptors resulting
      from the installation of four phosphonate groups at the upper rim of a
      calix[4]pyrrole-resorcin[4]arene hybrid scaffold. The isolated tetra-phosphonate
      receptors display either three (iooo) or four (oooo) of their P?O groups oriented
      away from the deep and functionalized aromatic cavity. In contrast to analogous
      tetra-phosphonate resorcin[4]arene cavitands, the 14-membered macrocyclic rings
      that contain the P?O groups in the tetra-phosphonate calix[4]pyrrole cavitands
      are conformationally flexible, always adopting a conformation locating the phenyl
      substituents in equatorial position. The tetra-phosphonate calix[4]pyrroles
      exhibited larger affinity constants than the previously reported bis-phosphonate
      calix[4]pyrrole counterparts in the complexation of both tetramethylphosphonium
      and octylammonium chloride salts in nonpolar solvents. We demonstrated that the
      iooo diastereoisomer was able to function as a multitopic receptor for organic
      chloride salts by switching the geometry of the 1:1 ion-paired complex from
      receptor-separated to close-contact depending on the quaternary or primary nature
      of the cobound organic cation. The ion-paired 1:1 complexes formed between the
      diastereomeric receptors and organic chloride salts were studied and
      thermodynamically characterized in solution. The determined stability constant
      values were compared to those obtained for the bis-phosphonate counterparts. The
      structure of the TMPCl?7iooo complex was determined by X-ray structure, and its
      formation was also evidenced in the gas phase. 

PMID- 25611528
TI  - Comparing graphene growth on Cu(111) versus oxidized Cu(111).
AB  - The epitaxial growth of graphene on catalytically active metallic surfaces via
      chemical vapor deposition (CVD) is known to be one of the most reliable routes
      toward high-quality large-area graphene. This CVD-grown graphene is generally
      coupled to its metallic support resulting in a modification of its intrinsic
      properties. Growth on oxides is a promising alternative that might lead to a
      decoupled graphene layer. Here, we compare graphene on a pure metallic to
      graphene on an oxidized copper surface in both cases grown by a single step CVD
      process under similar conditions. Remarkably, the growth on copper oxide, a high
      k dielectric material, preserves the intrinsic properties of graphene; it is not
      doped and a linear dispersion is observed close to the Fermi energy. Density
      functional theory calculations give additional insight into the reaction
      processes and help explaining the catalytic activity of the copper oxide surface.

PMID- 25611532
TI  - Picking your priorities: An educational pathway.

PMID- 25611531
TI  - Bridging the gap between acute and postacute care.

PMID- 25611533
TI  - Empowering float nurses.

PMID- 25611534
TI  - Ebola virus disease: Managing a practice challenge with evidence.

PMID- 25611535
TI  - Boost communication with EHRs.

PMID- 25611537
TI  - The value of certification: What do pediatric nurses think?

PMID- 25611538
TI  - Beyond belief...redefining spirituality.

PMID- 25611539
TI  - Leadership competencies to reduce health disparities.

PMID- 25611540
TI  - When leaders and instructors collide.

PMID- 25611541
TI  - Some pharmacokinetics of sevoflurane in a child with severe lipodystrophy.
AB  - Lipodystrophies are acquired or inherited disorders characterized in part by the
      selective loss of adipose tissue and hypertriglyceridemia. The present case
      report of 2 sevoflurane anesthetics given to a child with such a disorder, before
      and after correction of severe hypertriglyceridemia, illustrates the considerable
      effects of increased serum lipids and decreased fat stores on the
      pharmacokinetics of sevoflurane. 

PMID- 25611542
TI  - Editorial comment: some pharmacokinetics of sevoflurane in a child with severe
      lipodystrophy.

PMID- 25611543
TI  - Paradoxical air embolism to left anterior descending artery during induction of
      anesthesia in a patient with an atrial septal defect.
AB  - Systemic air embolism is a complication after IV injection of air bubbles
      adhering to IV tubing, 3-way injection ports, and residual air in drug-filled
      syringes. Paradoxical air embolism across an intracardiac septal defect is a well
      known complication, but paradoxical air embolism to the left coronary artery is a
      rare condition. We report the case of a 50-year-old woman scheduled for elective
      device closure of an atrial septal defect in whom coronary air embolism to the
      left anterior descending artery occurred after anesthetic induction. 

PMID- 25611544
TI  - Perioperative management of two patients with left ventricular assist devices
      presenting for noncardiac surgery in the prone position.
AB  - Ventricular assist devices (VADs) provide mechanical circulatory support for
      patients with advanced heart failure. Patients with VADs are presenting for
      noncardiac surgery with increasing frequency. Understanding anesthetic management
      of patients with VADs is timely and necessary for perioperative physicians. We
      present 2 patients supported by left VADs who required intraoperative prone
      positioning, and how transesophageal echocardiography and VAD variables can be
      used to guide management. 

PMID- 25611545
TI  - BF3.Et2O-promoted cleavage of the Csp-Csp2 bond of 2-propynolphenols/anilines:
      route to C2-alkenylated benzoxazoles and benzimidazoles.
AB  - A novel BF3.Et2O-promoted tandem reaction of easily prepared 2
      propynolphenols/anilines and trimethylsilyl azide is developed to give C2
      alkenylated benzoxazoles and benzimidazoles in moderate to good yields. Most
      reactions could be accomplished in 30 min at room temperature. This tandem
      process involves a Csp-Csp2 bond cleavage and a C-N bond formation. Moreover,
      both tertiary and secondary propargylic alcohols with diverse functional groups
      were tolerated under the mild conditions. 

PMID- 25611547
TI  - Occurrence of halogenated transformation products of selected pharmaceuticals and
      personal care products in secondary and tertiary treated wastewaters from
      southern California.
AB  - Final effluent samples from 10 southern California (United States) wastewater
      treatment facilities, employing four distinct treatment schemes, were surveyed
      for selected pharmaceuticals, personal care products (PPCPs), alkylphenols, and
      21 of their halogenated disinfection byproducts. Chlorinated and brominated
      standards and isotopically labeled internal standards were synthesized and
      purified to confirm and more accurately quantify selected disinfection byproducts
      of salicylic acid, bisphenol A, gemfibrozil, naproxen, diclofenac, technical 4
      nonylphenol, and 4-tert-octylphenol using high-performance liquid chromatography
      and tandem mass spectrometry. Concentrations of parent compounds ranged from <10
      to 3830 ng/L (gemfibrozil), and those of chloro/bromo byproducts ranged from <4
      to 370 ng/L (dibromo nonylphenol). The highest concentrations of parent compounds
      were measured in effluent that was not subjected to tertiary treatment. The
      chlorinated and brominated byproduct concentration may be affected by the
      influent concentration of parent compounds, hydraulic retention times, and
      chlorine contact times. Salicylic acid was readily halogenated, which is evident
      from the ratio of halogenated to nonhalogenated species. There were no measured
      chlorinated byproducts of bisphenol A despite occasionally high concentrations of
      the parent compound. Not surprisingly, higher concentrations of most brominated
      species were measured in the treatment plant with the highest bromide
      concentrations. These results demonstrate the occurrence of novel halogenated
      byproducts of PPCPs that have limited toxicological data and significant
      uncertainty with regard to their risk to ecological systems. 

PMID- 25611546
TI  - A computational approach to identifying gene-microRNA modules in cancer.
AB  - MicroRNAs (miRNAs) play key roles in the initiation and progression of various
      cancers by regulating genes. Regulatory interactions between genes and miRNAs are
      complex, as multiple miRNAs can regulate multiple genes. In addtion, these
      interactions vary from patient to patient and even among patients with the same
      cancer type, as cancer development is a heterogeneous process. These
      relationships are more complicated because transcription factors and other
      regulatory molecules can also regulate miRNAs and genes. Hence, it is important
      to identify the complex relationships between genes and miRNAs in cancer. In this
      study, we propose a computational approach to constructing modules that represent
      these relationships by integrating the expression data of genes and miRNAs with
      gene-gene interaction data. First, we used a biclustering algorithm to construct
      modules consisting of a subset of genes and a subset of samples to incorporate
      the heterogeneity of cancer cells. Second, we combined gene-gene interactions to
      include genes that play important roles in cancer-related pathways. Then, we
      selected miRNAs that are closely associated with genes in the modules based on a
      Gaussian Bayesian network and Bayesian Information Criteria. When we applied our
      approach to ovarian cancer and glioblastoma (GBM) data sets, 33 and 54 modules
      were constructed, respectively. In these modules, 91% and 94% of ovarian cancer
      and GBM modules, respectively, were explained either by direct regulation between
      genes and miRNAs or by indirect relationships via transcription factors. In
      addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively,
      were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in
      modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively.
      Finally, we extensively analyzed significant modules and showed that most genes
      in these modules were related to ovarian cancer and GBM. 

PMID- 25611548
TI  - Synthesis and characterization of functionally gradient materials obtained by
      frontal polymerization.
AB  - Functionally gradient materials (FGMs) with gradual and continuous changes of
      their properties in one or more dimensions are useful in a wide range of
      applications. However, obtaining such materials with accurate control of the
      gradient, especially when the gradient is nonlinear, is not easy. In this work,
      frontal polymerization (FP) was exploited to synthesize polymeric FGMs. We
      demonstrated that the use of ascending FP with continuous feeding of monomers
      with computer-controlled peristaltic pumps provided an excellent method for the
      preparation of functionally gradient materials with programmed gradients. To test
      the effectiveness of the method, copolymers made from triethylene glycol
      dimethacrylate/hexyl methacrylate with linear and hyperbolic gradient in
      composition were synthesized. Differential scanning calorimetry (DSC), Shore A
      hardness measurements, compression tests, and swelling studies were performed
      along the length of the materials to assess the relationship between the
      gradients and the material properties. Glass transition temperatures, determined
      by DSC, showed a linear dependence on the composition and were in agreement with
      theoretical values. The other properties showed different and specific behaviors
      as a function of the compositional gradient. 

PMID- 25611549
TI  - Theoretical study of structural changes in DNA under high external hydrostatic
      pressure.
AB  - The study of DNA under high hydrostatic pressure provides fundamental insights
      into the nature of interactions responsible for its structure and its remarkable
      stability in extreme conditions. We have investigated the structural changes in
      DNA under 2000 bar external pressure using electronic structure calculations and
      molecular dynamics simulations. Both these methods predict very small distortions
      in the structure; notably, the change in hydrogen bond lengths is an order of
      magnitude smaller than previously reported experimental values using NMR. The
      large discrepancy suggests further investigation into the analysis of the
      experimental data obtained from NMR. 

PMID- 25611550
TI  - Ordered mesoporous NiO with thin pore walls and its enhanced sensing performance
      for formaldehyde.
AB  - A class of formaldehyde (HCHO) gas sensors with a high response were developed
      based on ordered mesoporous NiO, which were synthesized via the nanocasting route
      by directly using mesoporous silica as the hard template. A series of mesoporous
      NiO with different textural parameters such as specific surface area, pore size,
      pore wall thickness were achieved by selecting mesoporous silica with different
      pore sizes as templates. The gas sensing properties for formaldehyde (HCHO) of
      the NiO specimens were examined. The results show that this mesoporous NiO
      possesses a much higher response to HCHO even at low concentration levels than
      the bulk NiO, and a larger specific surface area and pore size as well as thinner
      pore walls would be beneficial for enhancing the sensing properties of NiO. 

PMID- 25611551
TI  - The CD4 C868T Polymorphism and Its Correlation with HIV-1 Infection in a Chinese
      Population.
AB  - Previous studies performed in Kenya have suggested that the C868T single
      nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition;
      however, no relevant study has been conducted in China. To evaluate the influence
      of this SNP on risk of HIV-1 infection in a Chinese population, the CD4 genotype
      was determined by DNA sequencing in 101 HIV-1 patients and 102 healthy controls.
      No significant differences in the genotype and allele distributions of this
      polymorphism were observed among the patient and control groups. Additionally,
      binary logistic regression analyses adjusted by age and gender revealed that the
      C868T polymorphism was not associated with risk of HIV-1 infection. Furthermore,
      when analyses of genotype and allele frequencies were stratified by gender,
      similar nonsignificant results were found. Our study demonstrates a null
      association between the CD4 C868T polymorphism and an individual's susceptibility
      of HIV-1 acquisition in a Chinese population. Further studies are warranted to
      confirm these results. 

PMID- 25611553
TI  - Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and
      paracetamol: a population-based case-control study.
AB  - OBJECTIVE: To assess the risk of non-fatal ischemic stroke associated with non
      steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose,
      duration of treatment, background cardiovascular (CV) risk and use of concomitant
      aspirin were studied. METHODS: We performed a population-based case-control
      study. Patients were considered exposed if they were on treatment within a 30-day
      window before the index date. We estimated adjusted odds ratios (ORs) and their
      95% confidence intervals (CIs) using logistic regression. RESULTS: Two thousand
      eight hundred and eighty-eight cases and 20 000 controls were included. No
      increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95%
      CI, 0.90-1.19), but results varied across individual agents and conditions of
      use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97),
      in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term
      periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background
      CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high
      doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and
      in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found
      with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The
      concomitant use of aspirin did not show a significant effect modification.
      Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in
      patients at high CV risk (OR = 0.94; 0.78-1.14). CONCLUSIONS: Diclofenac and
      aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do
      not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate
      the risk. Paracetamol does not increase the risk, even in patients with a high
      background CV risk.

PMID- 25611552
TI  - Expression of BAF57 in ovarian cancer cells and drug sensitivity.
AB  - The SMARCE1 (SWI / SNF-related, matrix-associated, and actin-dependent regulator
      of chromatin, subfamily e, member 1) encodes BAF57 protein. Previously, we
      reported that BAF57 is a predictive marker of endometrial carcinoma. In this
      study, we investigated BAF57 expression in ovarian cancer cell lines and their
      sensitivities to cisplatin, doxorubicin, paclitaxel, and 5-fluorouracil. BAF57
      expression was strongly correlated with sensitivities to cisplatin, doxorubicin,
      and 5-fluorouracil in 10 ovarian cancer cell lines. Paclitaxel sensitivity was
      also correlated with BAF57 expression, but without significance. In A2780 ovarian
      cancer cells, knockdown of BAF57 using specific siRNA increased cell cycle arrest
      at G1 phase and the sensitivities to these anticancer agents. cDNA microarray
      analysis of A2780 cells transfected with BAF57 siRNA showed that 134 genes were
      positively regulated by BAF57, including ATP-binding cassette, sub-family G
      (WHITE), member 2 (ABCG2) encoding breast cancer resistance protein (BCRP). We
      confirmed that knockdown of BAF57 decreased BCRP expression in ovarian cancer
      cells by Western blot analysis, and that ABCG2 gene expression might be regulated
      transcriptionally. These results suggested that BAF57 is involved in ovarian
      cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a
      target for ovarian cancer therapy. 

PMID- 25611554
TI  - Rhodathiaborane reaction cycles driven by C2H4 and H2: synthesis and
      characterization of [(H)2(PPh3)RhSB8H7(PPh3)] and [(eta(2)
      C2H4)(PPh3)RhSB8H7(PPh3)].
AB  - New 10-vertex rhodathiaboranes are reported to exhibit reversible reaction
      chemistry leading to the formation of stoichiometric cycles driven by
      oxidation/reduction chemistry of the polyhedral boron-based clusters with
      ethelyne and dihydrogen. 

PMID- 25611555
TI  - Negative thermal quenching of photoluminescence in annealed ZnO-Al2O3 core-shell
      nanorods.
AB  - ZnO-Al2O3 core-shell nanorods (NRs) have been fabricated through the vapor phase
      condensation method and atomic layer deposition. It is found that the nanorod
      comprises a wurtzite single crystalline ZnO core with the main axes along the
      [0001] direction and an amorphous Al2O3 shell. The temperature-dependent
      photoluminescence (PL) properties of the as-grown and annealed ZnO/Al2O3 NRs are
      investigated systematically. The PL of the as-grown ZnO/Al2O3 NRs demonstrates a
      normal thermal quenching feature. However, the salient behavior of negative
      thermal quenching (NTQ), i.e., the increase in PL intensity with an increase in
      temperature, is clearly observed in the annealed ZnO/Al2O3 NRs. A multi-level
      model is adopted to account for this behavior and the thermal activation energy
      of the NTQ process is estimated to be ~69 meV. Moreover, we suggest that the
      activation energy is related to the Al donor defect in ZnO resulting from the
      inter-diffusion between the ZnO core and the Al2O3 shell during the annealing
      process. 

PMID- 25611556
TI  - Insect mating signal and mate preference phenotypes covary among host plant
      genotypes.
AB  - Sexual selection acting on small initial differences in mating signals and mate
      preferences can enhance signal-preference codivergence and reproductive isolation
      during speciation. However, the origin of initial differences in sexual traits
      remains unclear. We asked whether biotic environments, a source of variation in
      sexual traits, may provide a general solution to this problem. Specifically, we
      asked whether genetic variation in biotic environments provided by host plants
      can result in signal-preference phenotypic covariance in a host-specific, plant
      feeding insect. We used a member of the Enchenopa binotata species complex of
      treehoppers (Hemiptera: Membracidae) to assess patterns of variation in male
      mating signals and female mate preferences induced by genetic variation in host
      plants. We employed a novel implementation of a quantitative genetics method,
      rearing field-collected treehoppers on a sample of naturally occurring replicated
      host plant clone lines. We found remarkably high signal-preference covariance
      among host plant genotypes. Thus, genetic variation in biotic environments
      influences the sexual phenotypes of organisms living on those environments in a
      way that promotes assortative mating among environments. This consequence arises
      from conditions likely to be common in nature (phenotypic plasticity and
      variation in biotic environments). It therefore offers a general answer to how
      divergent sexual selection may begin. 

PMID- 25611559
TI  - Advanced heart failure, communication and the Goldilocks principle.

PMID- 25611560
TI  - Nurses and Lifelong Learning: Creating "Makers and Shapers" or "Users and
      Choosers"?
AB  - PROBLEM: How have the meaning and goals of lifelong learning for nurses shifted
      under neoliberal political policy? METHODS: This article critically scrutinizes
      the political undercurrents of lifelong learning. While the original intent of
      lifelong learning was to foster intellectual, critical, social, and political
      citizen engagement (creating "makers and shapers" of social policy), instrumental
      learning-learning to meet practical economic ends-has taken priority and is
      instead creating marketable workers (creating "users and choosers"). FINDINGS:
      International educational neoliberal policy reform has altered the very nature of
      education. Under pervasive neoliberal political influence, lifelong learning has
      become distorted as the goals of learning have shifted towards creating
      marketable workers who are expected, while unsupported, to engage in learning to
      ensure ongoing employability in an open market. CONCLUSIONS: By examining new
      understandings of lifelong learning, nurses can make informed choices as to
      whether they aspire to be a "user and chooser" or "maker and shaper" of lifelong
      learning in their workplaces.

PMID- 25611558
TI  - HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in
      autoimmune hepatitis type-1.
AB  - The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles
      are established autoimmune hepatitis (AIH) risk alleles. To study the immune
      modifying effect of these alleles, we imputed the genotypes from genome-wide
      association data in 649 Dutch AIH type-1 patients. We therefore compared the
      international AIH group (IAIHG) diagnostic scores as well as the underlying
      clinical characteristics between patients positive and negative for these HLA
      alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA
      DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher
      median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients
      (P<0.001). We did not observe associations between HLA alleles and alanine
      transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA
      DRB1*03:01 was independently associated with higher immunoglobulin G levels
      (P=0.04). The HLA-DRB1*04:01 allele was independently associated with
      presentation at older age (P=0.03) and a female predominance (P=0.04). HLA
      DRB1*03:01-positive patients received immunosuppressive medication and liver
      transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are
      both independently associated with the aggregate diagnostic IAIHG score in type-1
      AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the
      strongest genetic modifier of disease severity in AIH. 

PMID- 25611557
TI  - Deciphering the transcriptional switches of innate lymphoid cell programming: the
      right factors at the right time.
AB  - Innate lymphoid cells (ILCs) are increasingly recognised as an innate immune
      counterpart of adaptive T-helper (TH) cells. In addition to their similar
      effector cytokine production, there is a strong parallel between the
      transcription factors that control the differentiation of T(H)1, T(H)2 and T(H)17
      cells and ILC groups 1, 2 and 3, respectively. Here, we review the
      transcriptional circuit that specifies the development of a common ILC progenitor
      and its subsequent programming into distinct ILC groups. Notch, GATA-3 (GATA
      binding protein 3), Nfil3 (nuclear factor interleukin-3) and Id2 (inhibitor of
      DNA-binding 2) are identified as early factors that suppress B- and T-cell
      potentials and are turned on in favour of ILC commitment. Natural killer cells,
      which are the cytotoxic ILCs, develop along a pathway distinct from the rest of
      the helper-like ILCs that are derived from a common progenitor to all helper-like
      ILCs (CHILPs). PLZF(-) (promyelocytic leukaemia zinc-finger) CHILPs give rise to
      lymphoid tissue inducer cells, while PLZF(+) CHILPs have multilineage potential
      and could give rise to ILCs 1, 2 and 3. Such lineage specificity is dictated by
      the controlled expression of T-bet (T-box expressed in T cells), RORalpha
      (retinoic acid receptor-related orphan nuclear receptor-alpha), RORgammat
      (retinoic acid receptor-related orphan nuclear receptor-gammat) and AHR (aryl
      hydrocarbon receptor). In addition to the type of transcription factors, the
      developmental stages at which these factors are expressed are crucial in
      specifying the fate of the ILCs.

PMID- 25611561
TI  - The relationship between childhood adversity and food insecurity: 'It's like a
      bird nesting in your head'.
AB  - OBJECTIVE: Adverse childhood experiences, including abuse, neglect and household
      instability, affect lifelong health and economic potential. The present study
      investigates how adverse childhood experiences are associated with food
      insecurity by exploring caregivers' perceptions of the impact of their childhood
      adversity on educational attainment, employment and mental health. DESIGN: Semi
      structured audio-recorded in-person interviews that included (i) quantitative
      measures of maternal and child health, adverse childhood experiences (range: 0
      10) and food security using the US Household Food Security Survey Module; and
      (ii) qualitative audio-recorded investigations of experiences with abuse,
      neglect, violence and hunger over participants' lifetimes. SETTING: Households in
      Philadelphia, PA, USA. SUBJECTS: Thirty-one mothers of children <4 years old who
      reported low or very low household food security. RESULTS: Twenty-one caregivers
      (68 %) reported four or more adverse childhood experiences, and this severity was
      significantly associated with reports of very low food security (Fisher's exact
      P=0.021). Mothers reporting emotional and physical abuse were more likely to
      report very low food security (Fisher's exact P=0.032). Qualitatively,
      participants described the impact of childhood adverse experiences with emotional
      and physical abuse/neglect, and household substance abuse, on their emotional
      health, school performance and ability to maintain employment. In turn, these
      experiences negatively affected their ability to protect their children from food
      insecurity. CONCLUSIONS: The associations between mothers' adverse experiences in
      childhood and reports of current household food security should inspire
      researchers, advocates and policy makers to comprehensively address family
      hardship through greater attention to the emotional health of caregivers.
      Programmes meant to address nutritional deprivation and financial hardship should
      include trauma-informed approaches that integrate behavioural interventions.

PMID- 25611562
TI  - The use of novel diagnostics to individualize immunosuppression following
      transplantation.
AB  - Despite major improvements in short-term survival of organ allografts, long-term
      graft survival has not changed significantly. It is also known that toxic side
      effects of current immunosuppressive drugs (IS) especially calcineurin inhibitors
      (CNI) contribute to the unsatisfactory graft and patient survival following
      transplantation. Thus, clinicians strive to reduce or wean IS in potentially
      eligible patients. Research in the last 10 years has focussed on identification
      of biomarkers suitable for patient stratification in minimization or weaning
      trials. Most of the described biomarkers have been run retrospectively on samples
      collected within single-centre trials. Thus, often their performance has not been
      validated in other potentially multicentre clinical trials. Ultimately, the
      utility of biomarkers to identify potential weaning candidates should be
      investigated in large randomized prospective trials. In particular, for testing
      in such trials, we need more information about the accuracy, reproducibility,
      stability and limitations of the described biomarkers. Also, data repositories
      summarizing crucial information on biomarker performance in age- and gender
      matched healthy individuals of different ethnicity are missing. This together
      with improved bioinformatics tools might help in developing better scores for
      patient stratification. Here, we will summarize the current results, knowledge
      and limitations on biomarkers for drug minimization or weaning trials. 

PMID- 25611564
TI  - Fruit extract from a Sechium edule hybrid induce apoptosis in leukaemic cell
      lines but not in normal cells.
AB  - The antiproliferative potential of a crude extract from the chayote hybrid H-837
      07-GISeM(r) and its potential for apoptosis induction were assessed in leukaemic
      cell lines and normal mouse bone marrow mononuclear cells (BM-MNCs). The extract
      strongly inhibited the proliferation of the P388, J774, and WEHI-3 cell lines
      (with an IC50 below 1.3 MUg.mL(-1)), reduced cell viability, and induced
      apoptotic body production, phosphatidylserine translocation, and DNA
      fragmentation. However, the extract had no effect on BM-MNCs. We postulate that
      these properties make the extract a good candidate for an anti-tumour agent for
      clinical use. 

PMID- 25611563
TI  - Aggregation of poly(acrylic acid)-containing elastin-mimetic copolymers.
AB  - Polymer-peptide conjugates were produced via the copper-catalyzed azide-alkyne
      cycloaddition of poly(tert-butyl acrylate) (PtBA) and elastin-like peptides. An
      azide-functionalized polymer was produced via atom transfer radical
      polymerization (ATRP) followed by conversion of bromine end groups to azide
      groups. Subsequent reaction of the polymer with a bis-alkyne-functionalized,
      elastin-like peptide proceeded with high efficiency, yielding di- and tri-block
      conjugates, which after deprotection, yielded poly(acrylic acid) (PAA)-based
      diblock and triblock copolymers. These conjugates were solubilized in dimethyl
      formamide, and addition of phosphate buffered saline (PBS) induced aggregation.
      The presence of polydisperse spherical aggregates was confirmed by dynamic light
      scattering and transmission electron microscopy. Additionally, a coarse-grained
      molecular model was designed to reasonably capture inter- and intramolecular
      interactions for the conjugates and its precursors. This model was used to assess
      the effect of the different interacting molecular forces on the conformational
      thermodynamic stability of the copolymers. Our results indicated that the PAA's
      ability to hydrogen-bond with both itself and the peptide is the main interaction
      for stabilizing the diblocks and triblocks and driving their self-assembly, while
      interactions between peptides are suggested to play only a minor role on the
      conformational and thermodynamic stability of the conjugates. 

PMID- 25611565
TI  - Quercetin induces endoplasmic reticulum stress to enhance cDDP cytotoxicity in
      ovarian cancer: involvement of STAT3 signaling.
AB  - There is an urgent need to make cisplatin (cDDP) more effective and less toxic in
      the treatment of ovarian cancer for its systemic side effects and high resistance
      rate. In this study, we investigated the effect of quercetin (Qu) pretreatment on
      the potentiation of cDDP in ovarian cancer. We found that Qu pretreatment
      significantly enhanced cDDP cytotoxicity in an ovarian cancer cell line and
      primary cancer cells. In addition, we demonstrated that Qu elicited obvious
      endoplasmic reticulum stress (ERS) and activated all three branches of ERS in
      ovarian cancer. Specific inhibitors of each ERS pathway, as well as the general
      ERS stabilizer tauroursodeoxycholic acid, notably diminished such enhancing
      effects. Furthermore, Qu notably suppressed STAT3 phosphorylation, leading to
      downregulation of the BCL-2 gene downstream of STAT3. Moreover, blocking ERS
      restored the protein levels of phosphorylated STAT3 as well as BCL-2 expression,
      thus abolishing the chemosensitization potency of Qu; these results revealed that
      Qu affected the STAT3 pathway to enhance cDDP cytotoxicity, and this effect
      involved ERS signaling. In a xenograft mouse model of ovarian cancer, Qu enhanced
      the antitumor effect of cDDP. Tumors from mice treated with cDDP in combination
      with Qu pretreatment had repressed STAT3 phosphorylation, lower BCL-2 and higher
      apoptosis levels compared with those from the other groups. Meanwhile, Qu
      markedly reduced the elevation of blood creatinine during cDDP intervention.
      These data indicate that Qu pretreatment potentiates the antitumor effects of
      cDDP in ovarian cancer while protecting the kidneys against damage. Therefore the
      strategy of Qu pretreatment may be beneficial in enhancing the therapeutic
      efficacy of cDDP against ovarian cancer. 

PMID- 25611566
TI  - Plasma amino acid profiling in major depressive disorder treated with selective
      serotonin reuptake inhibitors.
AB  - AIMS: Amino acids are important body metabolites and seem to be helpful for
      understanding pathogenesis and predicting therapeutic response in major
      depressive disorder (MDD). We performed amino acid profiling to discover
      potential biomarkers in major depressive patients treated with selective
      serotonin reuptake inhibitors (SSRIs). METHODS: Amino acid profiling using
      aTRAQTM kits for Amino Acid Analysis in Physiological Fluids on a liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) system was performed on 158
      specimens at baseline and at 6 weeks after the initiation of SSRI treatment for
      68 patients with MDD and from 22 healthy controls. RESULTS: Baseline alpha
      aminobutyric acid (ABA) discriminated the patients according to the therapeutic
      response. Plasma glutamic acid concentration and glutamine/glutamic acid ratio
      were different between before and after SSRI treatment only in the response
      group. Comparing patients with MDD with healthy controls, alterations of ten
      amino acids, including alanine, beta-alanine, beta-aminoisobutyric acid,
      cystathionine, ethanolamine, glutamic acid, homocystine, methionine, O-phospho-L
      serine, and sarcosine, were observed in MDD. CONCLUSION: Metabolism of amino
      acids, including ABA and glutamic acid, has the potential to contribute to
      understandings of pathogenesis and predictions of therapeutic response in MDD.

PMID- 25611567
TI  - Prevalence of abnormal glycometabolism in treatment-naive patients with hepatitis
      C virus infection in a Chinese Han population.
AB  - BACKGROUND AND AIM: The hepatitis C virus (HCV) may promote pancreatic beta-cell
      apoptosis-like cell death through a caspase 3-dependent pathway, initiating the
      onset of type 2 diabetes mellitus (T2DM); however, the risk factors for
      development of T2DM and other abnormal glycometabolic factors in HCV patients of
      the Chinese Han ethnicity have been poorly explored. METHODS: A total of 947
      patients Chinese Han patients with confirmed HCV infection were enrolled in a
      multicenter study in order to examine the genetic and physiological parameters
      associated with the onset of abnormal glycometabolic conditions, including T2DM
      and prediabetes. RESULTS: HCV genotype 1b and host interleukin-28B CC genotype
      were most commonly observed. A total of 145 (15.3%) patients were diagnosed with
      T2DM and prediabetes. Elevated age, waist circumference, smoking duration, and
      systolic and diastolic blood pressure were shown to increase risks for abnormal
      glycometabolism. Liver dysfunction was shown to have positive correlations with
      abnormal glycometabolism in HCV patients. Genome-wide association studies
      indicated that certain genetic encoding inosine triphosphatase polymorphs
      (rs6051702) were associated with elevated risks for abnormal glycometabolism.
      Coupled with previous research data, it is likely that abnormal glycometabolism
      may be a useful predictor of risk for poor response to antiviral therapies and
      treatment-induced complications, such as anemia, in treatment naive patients.
      CONCLUSIONS: Abnormal glycometabolism and other such complications of HCV and HCV
      treatment may share critical metabolic and genetic pathways, providing
      potentially novel targets for future antiviral therapies for treatment resistant
      HCV genotypes.

PMID- 25611568
TI  - The Role for Optical Density in Heparin-Induced Thrombocytopenia: A Cohort Study.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious complication of
      heparin utilization. An enzyme-linked immunosorbent assay (ELISA) is usually
      performed to assist in the diagnosis of HIT. ELISAs tend to be sensitive but lack
      specificity. We sought to use a new cutoff to define a positive HIT ELISA.
      METHODS: We conducted a prospective observational study of hospitalized patients
      undergoing ELISA testing. All patients who underwent ELISA testing were eligible
      for inclusion (n = 496). Irrespective of the results, all subjects had
      confirmatory testing with a serotonin release assay (SRA). We compared a
      threshold optical density (OD) > 1.00 to the current definition of a positive
      ELISA (OD > 0.40) as a screening test for a positive SRA. We used sensitivity,
      specificity, and area under the receiver operating curve to determine whether an
      OD > 1.00 would improve diagnostic accuracy for HIT. RESULTS: The SRA was
      positive in 10 patients (prevalence, 2.0%). Adjusting the definition of a
      positive HIT ELISA to > 1.00 maintained the sensitivity and negative predictive
      value at 100% in the cohort. The positive predictive value of the higher cutoff
      OD was more than triple the positive predictive value of an OD > 0.40 (41.7% vs
      13.3%). No patient with a positive SRA had an OD measurement <= 1.00.
      CONCLUSIONS: Increasing the OD threshold enhances specificity without noticeably
      compromising sensitivity. Altering the definition of the HIT ELISA could prevent
      unnecessary testing and/or treatment with non-heparin-based anticoagulants in
      patients with possible HIT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00946400;
      URL: www.clinicaltrials.gov.

PMID- 25611569
TI  - Spectral Doppler interrogation of the pulmonary veins in atrial septal defect.
AB  - The various components of the pulmonary venous (PV) flow are linked to
      physiological and pathological changes that predominantly occur in the left
      heart. Thus, spectral Doppler interrogation of the PVs provides hemodynamic
      insight mainly into left-sided cardiac function. An exception to the dependence
      of PV flow on left heart events occurs in the setting of an atrial septal defect
      (ASD). The latter causes a portion of the PV blood flow, intended to cross the
      mitral valve, to be channeled into the more compliant right heart. This
      phenomenon makes the PV flow more dependent on the left-to-right interatrial
      shunt. The identification on the PV Doppler of a pattern that suggests uncoupling
      with left heart hemodynamics should raise the suspicion of an underlying ASD. 

PMID- 25611570
TI  - Primary cerebrospinal fluid diagnosis of pineal germinoma.

PMID- 25611571
TI  - Spatial organization of the tenascin-C microenvironment in experimental and human
      cancer.
AB  - The extracellular matrix (ECM) molecule tenascin-C (TNC) promotes tumor
      progression. This has recently been demonstrated in the stochastic murine RIP1
      Tag2 insulinoma model, engineered to either express TNC abundantly or to be
      devoid of TNC. However, our knowledge about organization of the TNC
      microenvironment is scant. Here we determined the spatial distribution of TNC
      together with other ECM molecules in murine RIP1-Tag2 insulinoma and human cancer
      tissue (insulinoma and colorectal carcinoma). We found that TNC is organized in
      matrix tracks together with other ECM molecules of the AngioMatrix signature, a
      previously described gene expression profile that characterizes the angiogenic
      switch. Moreover, stromal cells including endothelial cells, fibroblasts and
      leukocytes were enriched in the TNC tracks. Thus, TNC tracks may provide niches
      for stromal cells and regulate their behavior. Given similarities of TNC rich
      niches for stromal cells in human insulinoma and colon cancer, we propose that
      the RIP1-Tag2 model may be useful for providing insights into the contribution of
      the tumor stroma specific ECM as promoter of cancer progression.

PMID- 25611572
TI  - Highly sensitive and selective electrochemiluminescence determination of
      cholesterol utilizing a functional electrode with a core-shell nanostructure.
AB  - A highly sensitive and selective method for the determination of cholesterol is
      required to evaluate trace amounts of cholesterol in test samples. In this work,
      selected gold nanoparticles (AuNPs) and 5-amino-2-mercapto-1,3,4-thiadiazole
      (AMT) were used and a thin film of three-dimensional gold-AMT core-shell
      nanoparticles (p-AMT-AuNPs) was prepared using an electrochemical method.
      Cholesterol oxidase was then bonded to the film surface to give a functional
      electrode. Based on catalysis by the electrode functionalized for cholesterol and
      a luminol-H2 O2 electrochemiluminescence (ECL) system, a highly sensitive and
      selective ECL method was developed for the determination of cholesterol. Under
      optimized conditions, ECL intensity showed a good linear relationship with
      cholesterol over the concentration range 0.05-11.0 ug/ml, with a correlation
      coefficient of 0.999 and a limit of detection of 0.02 ug/ml. The proposed method
      was used to determine cholesterol in dairy products with a relative standard
      deviation of < 1.8% and recovery rates of 98.1-104%.

PMID- 25611574
TI  - Exploring the Effect of Mass Media on Perceptions of Infant Feeding.
AB  - This qualitative study explored women's perceptions of mass media and infant
      feeding. Mass media is a universal means of communication with potential to
      impact social norms. Data obtained from interviews with women (n = 20) were
      compared with text and visual representation from Internet sites (n = 12) on
      parenting and infant feeding. Themes from interviews reflected information
      represented on Internet sites. Participants offered suggestions for future media
      messages, such as public service announcements of breastfeeding. Participants
      emphasized that public opinion needs to be altered, and breastfeeding in public
      would then be viewed as the norm. 

PMID- 25611575
TI  - Testicular hypofunction caused by activating p53 expression induced by reactive
      oxygen species in varicocele rats.
AB  - We investigated the mechanism of the testicular hypofunction induced by hypoxia
      in varicocele rats. Varicocele was induced by partial ligation of the left renal
      vein. Seven weeks later, left testis mass index was measured. The sperm counts
      and motility were tested by CASA. The change of seminiferous tubule tissue was
      observed by HE staining. The reactive oxygen species (ROS) level in left
      testicular tissue was measured by ELISA, and the expressions of HIF-1alpha and
      p53 were detected by immunohistochemistry and Western blot. The left testis mass
      index and the sperm motility were significantly lower in surgery group. By HE
      staining, the left seminiferous epithelial cell arrangement was incompact,
      disordered and vacuolated in surgery group. The ROS level in surgery group was
      significantly higher than the other groups. The results of immunohistochemistry
      and Western blot indicated that the expressions of HIF-1alpha and p53 increased
      significantly in surgery group. Our study demonstrated that varicocele caused
      hypoxia that could cause the rise of ROS level to induce the increase of p53
      expression, leading to the decrease of testis mass index and changes of
      seminiferous tubules, which would reduce sperm motility and result in male
      infertility eventually. 

PMID- 25611573
TI  - Association of breast cancer risk loci with breast cancer survival.
AB  - The survival of breast cancer patients is largely influenced by tumor
      characteristics, such as TNM stage, tumor grade and hormone receptor status.
      However, there is growing evidence that inherited genetic variation might affect
      the disease prognosis and response to treatment. Several lines of evidence
      suggest that alleles influencing breast cancer risk might also be associated with
      breast cancer survival. We examined the associations between 35 breast cancer
      susceptibility loci and the disease over-all survival (OS) in 10,255 breast
      cancer patients from the National Cancer Institute Breast and Prostate Cancer
      Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We
      also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths,
      combining results from BPC3 and the Breast Cancer Association Consortium (BCAC)
      and performed in silico analyses of SNPs with significant associations. In BPC3,
      the C allele of LSP1-rs3817198 was significantly associated with improved OS
      (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend  = 2.84 * 10(-4) ; HRheterozygotes
      = 0.71; 95% CI: 0.55-0.92; HRhomozygotes  = 0.48; 95% CI: 0.31-0.76; p2DF  =
      1.45 * 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to
      increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C
      (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with
      increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend  = 6.6 * 10(-4) ;
      HRheterozygotes  = 0.96 95% CI: 0.90-1.03; HRhomozygotes  = 1.21; 95% CI: 1.09
      1.35; p2DF =1.25 * 10(-4) ). In conclusion, we show that there is little overlap
      between the breast cancer risk single nucleotide polymorphisms (SNPs) identified
      so far and the SNPs associated with breast cancer prognosis, with the possible
      exceptions of LSP1-rs3817198 and TNRC9-rs3803662.

PMID- 25611576
TI  - Array tomography: characterizing FAC-sorted populations of zebrafish immune cells
      by their 3D ultrastructure.
AB  - For 3D reconstructions of whole immune cells from zebrafish, isolated from adult
      animals by FAC-sorting we employed array tomography on hundreds of serial
      sections deposited on silicon wafers. Image stacks were either recorded manually
      or automatically with the newly released ZEISS Atlas 5 Array Tomography platform
      on a Zeiss FEGSEM. To characterize different populations of immune cells,
      organelle inventories were created by segmenting individual cells. In addition,
      arrays were used for quantification of cell populations with respect to the
      various cell types they contained. The detection of immunological synapses in
      cocultures of cell populations from thymus or WKM with cancer cells helped to
      identify the cytotoxic nature of these cells. Our results demonstrate the
      practicality and benefit of AT for high-throughput ultrastructural imaging of
      substantial volumes. 

PMID- 25611577
TI  - Retrospective analysis of the real-world use of the threshold suspend feature of
      sensor-augmented insulin pumps.
AB  - BACKGROUND: The automatic Threshold Suspend (TS) feature of the MiniMed 530G
      system (Medtronic MiniMed, Inc., Northridge, CA), when enabled, suspends insulin
      delivery for up to 2 h when the sensor glucose (SG) value reaches a preset
      threshold. MATERIALS AND METHODS: SG data from 20,973 patients who enabled the TS
      feature at their discretion and uploaded pump and sensor data to CareLink((r))
      (Medtronic MiniMed, Inc.) from October 15, 2013 to July 21, 2014 were analyzed.
      Comparisons between 758,382 patient-days wherein the TS feature was enabled at
      any time and 166,791 patient-days in which it was not enabled were made. Further
      comparisons were made between data collected during daytime (8:00 a.m. to 10:00
      p.m.) and nighttime (10:00 p.m. to 8:00 a.m.) hours. Data from subsets of
      patients who enabled the TS feature all of the time (n=14,673) versus those who
      never enabled the TS feature (n=2,249) were also compared. Recovery from
      hypoglycemia during and after 2-h pump suspension events was also assessed.
      RESULTS: The TS feature was enabled on 82% of patient-days. Patient-days in which
      the TS feature was enabled, compared with patient-days in which it was not, had
      69% fewer SG values <=50 mg/dL (0.64% vs. 2.09%, respectively; P<0.001). The
      reduction in hypoglycemia seen on TS-enabled days was more pronounced during
      nighttime than during daytime hours. SG data from full-time users of the TS
      feature reflected a 62% reduction in values <=50 mg/dL and a 5.6% reduction in
      values >=300 mg/dL compared with data from nonusers (P<0.001 for each). The
      median SG value at the start of 2-h suspensions was 60 (interquartile range
      [IQR], 57-66) mg/dL, immediately after was 87 (IQR, 63-123) mg/dL, and 4 h later
      was 164 (IQR, 117-220) mg/dL. CONCLUSIONS: The TS feature, when enabled
      consistently, reduced hypoglycemic exposure, and for those who had it enabled
      100% of the time, hyperglycemia was also reduced.

PMID- 25611580
TI  - Evolution of the mating system in colonizing plants.
AB  - Colonization is likely to be more successful for species with an ability to self
      fertilize and thus to establish new populations as single individuals. As a
      result, self-compatibility should be common among colonizing species. This idea,
      labelled 'Baker's law', has been influential in discussions of sexual-system and
      mating-system evolution. However, its generality has been questioned, because
      models of the evolution of dispersal and the mating system predict an association
      between high dispersal rates and outcrossing rather than selfing, and because of
      many apparent counter examples to the law. The contrasting predictions made by
      models invoking Baker's law versus those for the evolution of the mating system
      and dispersal urges a reassessment of how we should view both these traits. Here,
      I review the literature on the evolution of mating and dispersal in colonizing
      species, with a focus on conceptual issues. I argue for the importance of
      distinguishing between the selfing or outcrossing rate and a simple ability to
      self-fertilize, as well as for the need for a more nuanced consideration of
      dispersal. Colonizing species will be characterized by different phases in their
      life pattern: dispersal to new habitat, implying an ecological sieve on dispersal
      traits; establishment and a phase of growth following colonization, implying a
      sieve on reproductive traits; and a phase of demographic stasis at high density,
      during which new trait associations can evolve through local adaptation. This
      dynamic means that the sorting of mating-system and dispersal traits should
      change over time, making simple predictions difficult.

PMID- 25611583
TI  - Clinical obesity comes of age.

PMID- 25611582
TI  - Exercise improves quality of life in bariatric surgery candidates: results from
      the Bari-Active trial.
AB  - OBJECTIVE: To examine the impact of a pre-bariatric surgery physical activity
      intervention (PAI), designed to increase bout-related (>=10 min) moderate to
      vigorous PA (MVPA), on health-related quality of life (HRQoL). METHODS: Analyses
      included 75 adult participants (86.7% female; BMI = 45.0 +/- 6.5 kg m(-2)) who
      were randomly assigned to 6 weeks of PAI (n = 40) or standard pre-surgical care
      (SC; n = 35). PAI received 6 individual weekly counseling sessions to increase
      walking exercise. Participants wore an objective PA monitor for 7 days and
      completed the SF-36 Health Survey at baseline and post-intervention to evaluate
      bout-related MVPA and HRQoL changes, respectively. RESULTS: PAI increased bout
      related MVPA from baseline to post-intervention (4.4 +/- 5.5 to 21.0 +/- 21.4 min
      day(-1)) versus no change (7.9 +/- 16.6 to 7.6 +/- 11.5 min day(-1)) for SC (P =
      0.001). PAI reported greater improvements than SC on all SF-36 physical and
      mental scales (P < 0.05), except role-emotional. In PAI, better baseline scores
      on the physical function and general health scales predicted greater bout-related
      MVPA increases (P < 0.05), and greater bout-related MVPA increases were
      associated with greater post-intervention improvements on the physical function,
      bodily pain, and general health scales (P < 0.05). CONCLUSIONS: Increasing PA
      preoperatively improves physical and mental HRQoL in bariatric surgery
      candidates. Future studies should examine whether this effect improves surgical
      safety, weight loss outcomes, and postoperative HRQoL.

PMID- 25611584
TI  - Exploring the concept of eating dyscontrol in severely obese patients candidate
      to bariatric surgery.
AB  - Eating dyscontrol constitutes a potential negative predictor for the outcome of
      treatment strategies for obese patients. The aim of this study was to examine the
      qualitative characteristics of eating dyscontrol in obese patients who engage in
      binge eating (BE) compared with those who do not (NBE), and to analyse the
      relationship between eating dyscontrol and axis-I, axis-II, spectrum
      psychopathology using instruments that explore mood, panic-agoraphobic, social
      phobic, obsessive-compulsive and eating disorders spectrum psychopathology (SCI
      MOODS-SR, SCI-PAS-SR, SCI-SHY-SR, SCI-OBS-SR, SCI-ABS-SR). This was a cross
      sectional study involving a clinical sample of adult obese patients with severe
      obesity (average body mass index = 45 +/- 8 kg m(-2) ) and candidate to bariatric
      surgery who were recruited between November 2001 and November 2010 at the Obesity
      Center of the Endocrinology Unit, University Hospital of Pisa. All participants
      completed a face-to-face interview, including a diagnostic assessment of axes-I
      and II mental disorders (using the Structured Clinical Interview for Manual of
      Mental Disorders, fourth edition [SCID]-I and SCID-II) and filled out self-report
      spectrum instruments. Among obese patients not affected by BE, eating dyscontrol
      was highly represented. Indeed, 39.7% (N = 177) of subjects endorsed six or more
      items of the Anorexia-Bulimia Spectrum Self-Report, lifetime version domain
      exploring this behaviour. The cumulative probability of having axis-I, axis-II
      and a spectrum condition disorder increased significantly with the number of
      eating dyscontrol items endorsed. In both BE and NBE obese subjects, eating
      dyscontrol may represent an independent dimension strongly related to the
      spectrum psychopathology and axes I/II disorders. A systematic screening for
      eating dyscontrol symptoms by means of self-report spectrum instruments may be
      valuable to assign specific treatment strategies. 

PMID- 25611585
TI  - Baker's yeast (Saccharomyces cerevisiae) antigen in obese and normal weight
      subjects.
AB  - Baker's yeast (Saccharomyces cerevisiae) and its cell wall components have been
      used as one of the alternatives to antibiotic growth promoters in the feed
      industry. Antibodies to cell wall mannan of this yeast (ASCA) have been
      traditionally used in the study of Crohn's disease (CD). We applied ASCA in
      relation to obesity. This study aims (i) to determine the concentration of ASCA
      (immunoglobulin A [IgA] and immunoglobulin G [IgG]) in obese compared with normal
      weight individuals and (ii) to determine if there is a correlation between ASCA
      concentrations, obesity indices and C-reactive protein. Forty obese individuals
      (body mass index [BMI] > 35 kg m(-2) ) and 18 healthy (BMI < 25 kg m(-2) )
      volunteers participated in this case-control study. Binding activity of serum IgA
      and IgG to the cell wall mannan of S. cerevisiae was measured by enzyme-linked
      immunosorbent assay. More than one-third of the obese individual (35%) showed
      elevated titres of ASCA compared with the control group (5%). This antibody was
      positively associated with weight (P = 0.01), BMI (P = 0.02) and waist
      circumference (P = 0.02), but not with C-reactive protein. It seems that ASCA are
      not only specific for CD but are also associated with obesity. S. cerevisiae or a
      related antigen may play a role in the matrix of this complex condition. 

PMID- 25611586
TI  - The effect of therapeutic vaccination for the treatment of chronic hepatitis B
      virus infection.
AB  - Although oral nucleos(t)ide analogues can lead to suppression of serum hepatitis
      B virus (HBV) DNA to undetectable levels efficiently, they usually fail to
      achieve seroclearance of hepatitis B surface antigen (HBsAg), which indicates
      eradication of HBV infection. In this study, the efficacy of therapeutic
      vaccination in patients with chronic HBV infection was evaluated by comparing to
      the control patients. Patients who had achieved complete virologic response
      following oral nucleos(t)ide analogue treatment for at least 6 months were
      included. Vaccinated patients were given three intramuscular injections of
      hepatitis B vaccine that each contains 20 ug of HBsAg. The efficacy of
      vaccination was assessed by testing for HBsAg seroclearance. A total of 32
      consecutive patients were analyzed, which included 15 vaccinated patients and 17
      control patients. At month 6, 1 out of 15 vaccinated patients (6.7%) and 1 out of
      17 control patients (5.9%) were determined to clear HBsAg from their sera (P =
      1.000). A baseline HBsAg titer of <=100 IU/mL tended to be predictive of HBsAg
      seroclearance, but the relationship was not significant (P = 0.097). During the
      follow-up period, virologic relapse occurred in 29 patients, and 9 patients
      developed hepatitis flare. The cumulative incidences of virologic relapse and
      hepatitis flare were similar between the vaccinated and control patients (P =
      0.077 and P = 0.667, respectively). In conclusion, therapeutic HBV vaccination in
      patients who had stopped nucleos(t)ide analogue treatment showed limited efficacy
      for HBsAg seroclearance. To enhance the efficacy and safety of therapeutic HBV
      vaccination, rational patient selection and novel therapeutic approaches are
      needed.

PMID- 25611588
TI  - Hyaluronan dermal fillers via crosslinking with 1,4-butandiol diglycidyl ether:
      Exploitation of heterogeneous reaction conditions.
AB  - Most of hyaluronan (HA)-based dermal fillers currently available on the market
      are produced through biopolymer crosslinking with 1,4-butandiol diglycidyl ether
      (BDDGE). Chemical modification is usually performed on the biopolymer dissolved
      in a highly alkaline aqueous medium (homogeneous conditions). Heterogeneous
      conditions for HA reaction with BDDGE were exploited here to obtain competitive
      HA fillers and to assess potential improvements in production process. Optimal
      parameters for effective reaction accomplishment were evaluated (e.g., medium
      composition, temperature and time of reaction). HA was modified with increasing
      BDDGE/HA equivalents (7-14%) achieving 66-74% (w/w) biopolymer insolubility.
      Hydrogels exhibited high swelling extent and outstanding resistance to enzymatic
      degradation decreasing and improving according to crosslinking degree,
      respectively. Once suspended in physiological solution (20 mg/mL), these products
      directly formed easy-to-extrude gels through 27-29 G needles. Gel particle
      dimensions were in the range 10-1000 um. Rheological analyses revealed decreasing
      viscosity with the shear rate and G' values in the range 1200-1700 Pa. Overall,
      results of the in vitro characterization demonstrated the attainment of
      crosslinked HA particles suitable for application as dermal fillers. These new
      gels proved superior to similar commercialized products in terms of stability to
      enzymatic hydrolysis. Further, the protocol assessed allowed interesting
      improvements over conventional manufacturing procedures.

PMID- 25611587
TI  - Chronic filarial infection provides protection against bacterial sepsis by
      functionally reprogramming macrophages.
AB  - Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory
      milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation
      may benefit sepsis outcome by preventing exacerbated inflammation and severe
      pathology, but the influence on bacterial clearance remains unclear. To address
      this, mice were chronically infected with the filarial nematode Litomosoides
      sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p.
      Escherichia coli injection was determined. L.s. infection significantly improved
      E. coli-induced hypothermia, bacterial clearance and sepsis survival and
      correlated with reduced concentrations of associated pro-inflammatory
      cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene
      expression profile. Improved sepsis outcome in L.s.-infected animals was mediated
      by macrophages, but independent of the alternatively activated macrophage subset.
      Endosymbiotic Wolbachia bacteria that are present in most human pathogenic
      filariae, as well as L.s., signal via TLR2 and modulate macrophage function.
      Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice
      revealed a downregulation of genes involved in TLR signaling, and pulsing of
      macrophages in vitro with L.s. extract reduced LPS-triggered activation.
      Subsequent transfer improved sepsis outcome in naive mice in a Wolbachia- and
      TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from
      L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s.
      infection neither improved bacterial clearance in TLR2-deficient animals nor
      ameliorated E. coli-induced hypothermia and sepsis survival. These results
      indicate that chronic L.s. infection has a dual beneficial effect on bacterial
      sepsis, reducing pro-inflammatory immune responses and improving bacterial
      control. Thus, helminths and their antigens may not only improve the outcome of
      autoimmune and allergic diseases, but may also present new therapeutic approaches
      for acute inflammatory diseases that do not impair bacterial control. 

PMID- 25611589
TI  - Conjugation of estrone glucuronide with human lysozyme.
AB  - Human milk lysozyme was conjugated with estrone glucuronide to give a
      monoacylated conjugate, two disubstituted isoforms, and one trisubstituted
      isoform in 99.4% yield. The conjugates were pure and highly inhibited (>98%) by
      the anti-estrone glucuronide antibody. The clearing curves were biphasic for all
      four conjugates but a 3 min initial rate assay was established and used to
      measure a normal menstrual cycle profile of estrone glucuronide excretion rates.
      The marked differences between the hen egg white and human milk lysozyme
      conjugates show that near identical tertiary structures do not necessarily imply
      similar physical, chemical, biochemical, and kinetic behavior. 

PMID- 25611590
TI  - In vitro and in vivo identification of metabolites of magnoflorine by LC LTQ
      Orbitrap MS and its potential pharmacokinetic interaction in Coptidis Rhizoma
      decoction in rat.
AB  - Magnoflorine, an important aporphine alkaloid in Coptidis Rhizoma, is
      increasingly attracting research attention because of its pharmacological
      activities. The in vivo and in vitro metabolism of magnoflorine was investigated
      by LC LTQ-Orbitrap MS. In vivo samples including rat urine, feces, plasma and
      bile were collected separately after both oral (50 mg kg(-1) ) and intravenous
      administration (10 mg kg(-1) ) of magnoflorine, along with in vitro samples
      prepared by incubating magnoflorine with rat intestinal flora and liver
      microsome. As a result, 12 metabolites were found in biological samples. Phase I
      metabolites were identified in all biological samples, while phase II metabolites
      were mainly detected in urine, plasma and bile. In a pharmacokinetic study, rats
      were not only dosed with magnoflorine via oral (15, 30 and 60 mg kg(-1) ) and
      intravenous administration (10 mg kg(-1) ) but also dosed with Coptidis Rhizoma
      decoction (equivalent to 30 mg kg(-1) of magnoflorine) by intragastric
      administration to investigate the interaction of magnoflorine with the rest of
      compounds in Coptidis Rhizoma. Studies showed that magnoflorine possessed lower
      bioavailability and faster absorption and elimination. However, pharmacokinetic
      parameters altered significantly (p < 0.05) when magnoflorine was administered in
      Coptidis Rhizoma decoction. Oral gavage of Coptidis Rhizoma decoction decreased
      the absorption and elimination rates of magnoflorine, which revealed that there
      existed pharmacokinetic interactions between magnoflorine and the rest of
      ingredients in Coptidis Rhizoma.

PMID- 25611591
TI  - Catalytic enantioselective [5+2] cycloaddition between oxidopyrylium ylides and
      enals under dienamine activation.
AB  - Benzopyrylium ylides generated in situ from 1-acetoxyisochroman-4-ones reacted
      with alpha,beta-unsaturated aldehydes in the presence of a bifunctional secondary
      amine/squaramide catalyst to furnish [5+2] cycloaddition products in good yield
      with high diastereo- and enantioselectivity. The reaction proceeds by dienamine
      activation and involves beta,gamma-functionalization of the enal. The dienamine
      intermediates showed exclusive beta,gamma-reactivity and provided direct access
      to compounds with the 8-oxabicyclo[3.2.1]octane framework. The ability of the
      bifunctional secondary-amine/squaramide catalyst to engage in hydrogen-bonding
      interactions with the ylide made it particularly effective in terms of both the
      yield and the stereoselectivity of the transformation. 

PMID- 25611593
TI  - Increased coupling of caveolin-1 and estrogen receptor alpha contributes to the
      fragile X syndrome.
AB  - OBJECTIVE: Fragile X syndrome (FXS) is a form of inherited mental retardation in
      humans that results from expansion of a CGG repeat in the FMR1 gene. Interaction
      between estrogen receptor (ER) and lipid raft caveolae is critical for the
      estrogen signaling. Here, we tested the hypothesis that impaired ER-caveolae
      coupling contributes to the mental retardation of FXS. METHODS: Fmr1 knockout
      (KO) mouse was used as the model of FXS. Multiple techniques were performed
      including primary neuronal culture, short hairpin RNA (shRNA) interference,
      Western blot, electrophysiological recording, RNA-binding protein
      immunoprecipitation, reverse transcriptase polymerase chain reaction, and
      behavioral tests. RESULTS: In this study, we report that GluA1 surface expression
      and phosphorylation induced by 17beta-estradiol (E2) were impaired in the Fmr1 KO
      neurons. The E2-mediated facilitation of long-term potentiation and fear memory
      was impaired in the anterior cingulate cortex of Fmr1 KO mice. The increased
      coupling of caveolin-1 (CAV1) and the membrane estrogen receptor ERalpha under
      basal conditions contributed to the impairment of ER signaling in Fmr1 KO
      neurons. FMRP (fragile X mental retardation protein) interacted with CAV1 mRNA,
      and knockdown of CAV1 with shRNA rescued the synaptic GluA1 delivery, plasticity,
      and memory in Fmr1 KO mice. INTERPRETATION: This is the first demonstration that
      the coupling between ERalpha and lipid raft CAV1 is critical for membrane ER
      signaling in synaptic plasticity. Therefore, increased coupling of CAV1 and
      ERalpha may elucidate a critical abnormal mechanism of FXS.

PMID- 25611592
TI  - Deficiency in thrombopoietin induction after liver surgery is associated with
      postoperative liver dysfunction.
AB  - BACKGROUND AND AIMS: Thrombopoietin (TPO) has been implicated in the process of
      liver regeneration and was found to correlate with hepatic function in patients
      with liver disease. With this investigation we aimed to determine if
      perioperative TPO levels were associated with postoperative outcome in patients
      undergoing liver resection. METHODS: Perioperative TPO was analyzed prior to
      liver resection as well as on the first and fifth postoperative day in 46
      colorectal cancer patients with liver metastasis (mCRC) as well as 23
      hepatocellular carcinoma patients (HCC). Serum markers of liver function within
      the first postoperative week were used to define liver dysfunction. RESULTS:
      While circulating TPO levels significantly increased one day after liver
      resection in patients without liver cirrhosis (mCRC) (P < 0.001), patients with
      underlying liver disease (HCC) failed to significantly induce TPO
      postoperatively. Accordingly, HCC patients had significantly lower TPO levels on
      POD1 and 5. Similarly, patients with major resections failed to increase
      circulating TPO levels. Perioperative dynamics of TPO were found to specifically
      predict liver dysfunction (AUC: 0.893, P < 0.001) after hepatectomy and remained
      an independent predictor upon multivariate analysis. CONCLUSIONS: We here
      demonstrate that perioperative TPO dynamics are associated with postoperative LD.
      Postoperative TPO levels were found to be lowest in high-risk patients (HCC
      patients undergoing major resection) but showed an independent predictive value.
      Thus, a dampened TPO increase after liver resection reflects a poor capacity for
      hepatic recovery and may help to identify patients who require close monitoring
      or intervention for potential complications.

PMID- 25611594
TI  - Forecasted coral reef decline in marine biodiversity hotspots under climate
      change.
AB  - Coral bleaching events threaten coral reef habitats globally and cause severe
      declines of local biodiversity and productivity. Related to high sea surface
      temperatures (SST), bleaching events are expected to increase as a consequence of
      future global warming. However, response to climate change is still uncertain as
      future low-latitude climatic conditions have no present-day analogue. Sea surface
      temperatures during the Eocene epoch were warmer than forecasted changes for the
      coming century, and distributions of corals during the Eocene may help to inform
      models forecasting the future of coral reefs. We coupled contemporary and Eocene
      coral occurrences with information on their respective climatic conditions to
      model the thermal niche of coral reefs and its potential response to projected
      climate change. We found that under the RCP8.5 climate change scenario, the
      global suitability for coral reefs may increase up to 16% by 2100, mostly due to
      improved suitability of higher latitudes. In contrast, in its current range,
      coral reef suitability may decrease up to 46% by 2100. Reduction in thermal
      suitability will be most severe in biodiversity hotspots, especially in the Indo
      Australian Archipelago. Our results suggest that many contemporary hotspots for
      coral reefs, including those that have been refugia in the past, spatially
      mismatch with future suitable areas for coral reefs posing challenges to
      conservation actions under climate change.

PMID- 25611595
TI  - Serial position markers in space: visuospatial priming of serial order working
      memory retrieval.
AB  - Most general theories on serial order working memory (WM) assume the existence of
      position markers that are bound to the to-be-remembered items to keep track of
      the serial order. So far, the exact cognitive/neural characteristics of these
      markers have remained largely underspecified, while direct empirical evidence for
      their existence is mostly lacking. In the current study we demonstrate that
      retrieval from verbal serial order WM can be facilitated or hindered by spatial
      cuing: begin elements of a verbal WM sequence are retrieved faster after cuing
      the left side of space, while end elements are retrieved faster after cuing the
      right side of space. In direct complement to our previous work--where we showed
      the reversed impact of WM retrieval on spatial processing--we argue that the
      current findings provide us with a crucial piece of evidence suggesting a direct
      and functional involvement of space in verbal serial order WM. We outline the
      idea that serial order in verbal WM is coded within a spatial coordinate system
      with spatial attention being involved when searching through WM, and we discuss
      how this account can explain several hallmark observations related to serial
      order WM.

PMID- 25611596
TI  - Patterns of bisphosphonates utilization in patients under age 45 in a large
      cohort of commercial insurance beneficiaries in the United States.
AB  - BACKGROUND: The effectiveness and safety of bisphosphonates treatment used in the
      young population have not been well studied. Despite insufficient data on
      effectiveness and safety of bisphosphonates in young patients, bisphosphonates
      are still considered in younger patients at high risk for osteoporosis or
      fracture. The objectives of this study were to identify bisphosphonate initiators
      aged 10-45 years and describe their clinical characteristics and to assess time
      trends of bisphosphonate use over the past decade in a large U.S. population
      based cohort. METHODS: Using the medical and pharmacy claims data from a U.S.
      commercial insurance (2003-2012), patients aged 10-45 years without malignancy
      who initiated an oral or intravenous bisphosphonate after at least 1 year of
      insurance enrollment were selected. Baseline demographics, comorbidities,
      medications and health care utilization were assessed in the year prior to
      initiating a bisphosphonate. The trend of bisphosphonate use over time was
      examined. RESULTS: There were 9,082 bisphosphonate initiators (0.02% of the same
      age group in the population). The mean age was 38.1 years and 79.6% female.
      Osteoporosis was the most common diagnosis (41.2%). At baseline, 10.8% had a
      diagnosis of fracture and 29.0% had a bone mineral density measured. Of those who
      used glucocorticoids (39%) at baseline, the mean 1-year cumulative prednisone
      equivalent dose was 2,669 milligrams. The use of bisphosphonates in the young
      population significantly decreased over the past decade (p<0.001). CONCLUSIONS:
      Among young patients aged 10-45, the use of bisphosphonates was uncommon and
      significantly decreased over the past decade in the U.S. While most patients
      initiating bisphosphonates had a diagnosis of osteoporosis and fracture in the
      preceding year, some had no recorded claims with a diagnosis of fracture,
      osteoporosis, or long-term glucocorticoids use at baseline. Future research is
      needed to examine the effectiveness and safety of bisphosphonates in young
      patients at risk for osteoporosis.

PMID- 25611597
TI  - Effectiveness of standardized approach versus usual care on physiotherapy
      treatment for patients submitted to alveolar bone graft: a pilot study.
AB  - AIM: To compare the acute effects of a standardized physiotherapy protocol versus
      a typical non-standardized physiotherapy protocol on pain and performance of
      patients undergoing alveolar bone graft (ABG). METHOD: Sixteen patients (9 males;
      12 [11-13] years) with cleft lip and palate undergoing ABG were allocated into
      two groups: (1) experimental group--EG (standardized physiotherapy protocol); and
      (2) control group--CG (typical, non-standardized physiotherapy treatment). Range
      of motion, muscle strength, gait speed, and pain level were assessed prior to
      surgical intervention (PRE), as well as on the first, second, and third post
      operative days (1st, 2nd, and 3rd PO, respectively). RESULTS: Recovery with
      respect to range of motion of hip flexion was more pronounced in the EG (64.6 +/-
      11.0 degrees ) in comparison to the CG (48.5 +/- 17.7 degrees  on the 3rd PO; p <
      0.05). In addition, less pain was observed in the EG (0 [0-0.2] versus 2 [0.7-3]
      in the CG on the 3rd PO; p < 0.05). CONCLUSION: A standardized physiotherapy
      protocol appears to be better than a non-standardized physiotherapy protocol for
      acute improvement of range of motion of hip flexion and for reducing pain in
      patients undergoing ABG.

PMID- 25611598
TI  - Descriptive analysis of common functional limitations identified by patients with
      shoulder pain.
AB  - CONTEXT: Recent establishment of G-codes by the US government requires therapists
      to report function limitations at initial evaluation. Limited information exists
      specific to the most common limitations in patients with shoulder pain.
      OBJECTIVE: To describe the most commonly expressed shoulder limitations with
      activities and their severity/level of impairment from a patient's perspective on
      the initial evaluation. DESIGN: Descriptive. SETTING: Patients reporting pain
      with overhead activity and seeking medical attention from one orthopedic surgeon
      were recruited as part of a cohort study. PATIENTS: 176 with shoulder superior
      labral tear from anterior to posterior (SLAP), subacromial impingement, combined
      SLAP and rotator cuff, and nonspecific (female = 53, age = 41 +/- 13 y; male =
      123, age = 41 +/- 12 y). INTERVENTIONS: Data were obtained on the initial visit
      from the Patient-Specific Functional Scale (PSFS) questionnaire. Three
      researchers extracted meaningful concepts from the PSFS and linked them to the
      International Classification of Functioning (ICF) categories according to
      established ICF linking rules. RESULTS: 176 participants yielded 765 meaningful
      concepts that were linked to the ICF with a 66% agreement between researchers
      before consensus. There were no differences between diagnoses. Of all patients,
      88% reported functional limitations coded into meaningful concepts as represented
      by 10 ICF codes; 634 (83%) meaningful concepts were linked to the activities and
      participation domain while 129 (17%) were linked to the body function domain.
      Only 2 reported functional limitations that were considered nondefinable (nd).
      The overall average initial impairment score on the PSFS = 4 +/- 2.5 out of 10
      points. CONCLUSION: Meaningful concepts from the activities and participation
      domain were most commonly identified as functional limitations and were more
      prevalent than limitations from the body function domain. This information helps
      identify some of the most common limitations in patients with shoulder pain that
      therapists can use to efficiently document patient functional impairment.

PMID- 25611599
TI  - Welcome to a&a case reports.

PMID- 25611600
TI  - Dental extraction in a child with chronic idiopathic thrombocytopenia purpura:
      are preoperative platelet transfusions necessary?
AB  - Thresholds for platelet counts in patients at risk for bleeding are often used
      before surgery. We present a case report of a 13-year-old female with chronic
      idiopathic thrombocytopenia purpura for dental extraction with a platelet count
      of 4 * 10 L. Usually, therapies including platelet infusions, IV immunoglobulin,
      or corticosteroids would be used to increase platelet numbers. In this patient,
      rather than using any of these prophylactic therapies preoperatively, we used a
      "watchful waiting" strategy with a multidisciplinary team, the use of tranexamic
      acid and the aforementioned therapies available only as "rescue" agents. 

PMID- 25611601
TI  - Perioperative management of a child with glutaric aciduria type I undergoing
      cardiac surgery.
AB  - Patients with glutaric aciduria type I are at risk for acute striatal injury
      precipitated by catabolic stress. Here, we report the successful
      interdisciplinary anesthetic and perioperative management of a child with
      glutaric aciduria type I undergoing cardiac surgery with extracorporeal
      circulation. Given the central focus on prevention of acute striatal injury, our
      anesthetic strategy emphasized avoiding a high protein load, high-dose
      inotropics, especially epinephrine (associated with impaired glucose
      utilization), deliberate hyperventilation, and other interventions associated
      with systemic inflammatory response. 

PMID- 25611602
TI  - Spontaneous hyphema in a patient undergoing laparoscopic appendectomy.
AB  - Hyphema, an ophthalmic pathology characterized by blood accumulation in the
      anterior chamber of the eye, has never been linked to administration of general
      anesthesia. We present the case of a spontaneous hyphema occurring on emergence
      from general anesthesia in a postlaparoscopic appendectomy patient. A valsalva
      like maneuver with breath-holding during stage II of emergence or during CO2
      insufflation may have led to the development of hyphema. 

PMID- 25611603
TI  - Intensification of a chemical burn injury by a warming device combined with the
      tissue pressure in the operating room.
AB  - A 19-year-old girl suffered an unexpected gasoline-associated chemical burn
      injury that may have been intensified by a warming device and tissue pressure in
      the operating room. Anesthesiologists should be aware that serious skin injury
      may result from combination of cutaneous exposure to hydrocarbons, especially
      when warming devices are simultaneously used. 

PMID- 25611604
TI  - Telogen effluvium need not recur.
AB  - Hair loss after surgery has many causes. If the onset is acute and it lasts for
      several months, it is often attributed to telogen effluvium. A case is presented
      where hair loss occurred after a surgical procedure, but it did not recur after a
      subsequent procedure with a similar anesthetic. 

PMID- 25611605
TI  - Anesthetic management for cesarean delivery of a parturient with impetigo
      herpetiformis.
AB  - Impetigo herpetiformis (IH), or generalized pustular psoriasis of pregnancy, is
      an exceedingly rare, generalized pustular skin eruption occurring during
      pregnancy associated with hypovolemia, sepsis, hypocalcemia, and airway edema.
      Fetal outcomes are generally poor, and parturients with IH may present with
      emergent indications for cesarean delivery due to placental insufficiency. We
      present a case of IH in a 19-year-old G1P0 who underwent successful general
      anesthesia for cesarean delivery. Her case highlights the anesthetic implications
      for patients afflicted with this rare disease, including perioperative pain
      management, airway concerns, considerations for neuraxial anesthesia, and
      monitoring challenges. 

PMID- 25611606
TI  - Sequential bilateral lung isolation with a single bronchial blocker.
AB  - Sequential bilateral lung separation and selective lung collapse can be
      accomplished with either a double-lumen tube, a single bronchial blocker (BB)
      that must be repositioned during the operation, or by using 2 BBs, 1 placed in
      each main bronchus. We provided sequential bilateral lung collapse using a single
      BB without the need to reposition during surgery. 

PMID- 25611607
TI  - Rapid onset of guillain-barre syndrome after an obstetric epidural block.
AB  - Reports of acute onset of Guillain-Barre syndrome (GBS) after epidural
      anesthesia/analgesia after labor and cesarean delivery has raised concern of a
      correlation between GBS and the use of neuraxial anesthesia. We present a patient
      who developed bilateral lower extremity weakness and paraparesis within hours
      after removal of an epidural catheter for cesarean delivery. The clinical
      diagnosis was highly suggestive for GBS after magnetic resonance imaging,
      cerebrospinal fluid findings, electromyogram, and nerve conduction studies. We
      discuss the pathophysiological mechanisms suggested in previous case reports and
      describe the relationship between epidural analgesia and GBS. 

PMID- 25611608
TI  - Awake Tracheal Intubation in an 8-Year-Old Girl with McCune-Albright Syndrome.
AB  - An 8-year-old girl with McCune-Albright syndrome presented for resection of a
      very large fibrous dysplasia mass of the face with significant distortion of the
      airway anatomy. She had significant obstructive sleep apnea with daytime
      somnolence and hemoglobin oxygen desaturations while breathing room air
      preoperatively. We were able to successfully manage her airway by providing IV
      sedation, topical anesthesia of the airway, and oral fiberoptic intubation in
      close collaboration with our otorhinolaryngology colleagues. 

PMID- 25611609
TI  - Occurrence of severe hypotension after indocyanine green injection during the
      intraoperative period.
AB  - Indocyanine green (ICG) is generally considered to be safe for IV administration
      and has a very low incidence of complications. We report 2 cases of severe
      hypotension immediately after low dose administration of IV ICG. The first case
      is a 69-year-old woman who developed severe hypotension after a second 5 mg IV
      bolus of ICG given shortly after the placement of an aneurysm clip during an
      otherwise uneventful surgery performed under general anesthesia. The second case
      is a 56-year-old woman with moyamoya disease who became hypotensive subsequent to
      a 2.5 mg ICG bolus at the conclusion of an external-carotid to internal-carotid
      bypass procedure under general anesthesia. Anesthesiologists and surgeons are
      increasingly likely to encounter or request the intraoperative administration of
      ICG, and they need to be aware of this potential for an adverse reaction,
      particularly with the repeated doses. Anesthesia and other intraoperative
      conditions may mask the typically mild adverse reactions usually associated with
      ICG. 

PMID- 25611611
TI  - Controlling the reproducibility of Coulomb blockade phenomena for gold
      nanoparticles on an organic monolayer/silicon system.
AB  - Two types of highly ordered organic layers were prepared on silicon modified with
      an amine termination for binding gold nanoparticles (AuNPs). These two grafted
      organic monolayers (GOMs), consisting of alkyl chains with seven or 11 carbon
      atoms, were grafted on oxide-free Si(111) surfaces as tunnel barriers between the
      silicon electrode and the AuNPs. Three kinds of colloidal AuNPs were prepared by
      reducing HAuCl4 with three different reactants: citrate (Turkevich synthesis,
      diameter ~16 nm), ascorbic acid (diameter ~9 nm), or NaBH4 (Natan synthesis,
      diameter ~7 nm). Scanning tunnel spectroscopy (STS) was performed in a UHV STM at
      40 K, and Coulomb blockade behaviour was observed. The reproducibility of the
      Coulomb behavior was analysed as a function of several chemical and physical
      parameters: size, crystallinity of the AuNPs, influence of surrounding surfactant
      molecules, and quality of the GOM/Si interface (degree of oxidation after the
      full processing). Samples were characterized with scanning tunneling microscope,
      STS, atomic force microscope, Fourier transform infrared spectroscopy, x-ray
      photoelectron spectroscopy (XPS), and high resolution transmission electronic
      microscope. We show that the reproducibility in observing Coulomb behavior can be
      as high as ~80% with the Natan synthesis of AuNPs and GOMs with short alkyl
      chains.

PMID- 25611612
TI  - Migration of pediatric epidural catheters.
AB  - BACKGROUND: Postoperative pain control in the pediatric population frequently
      involves epidural catheters placed intraoperatively. A retrospective review of
      epidural catheter tip position was conducted by evaluation of routine chest
      anterior-posterior (A-P) X-rays obtained by the surgical and ICU teams. METHODS:
      Of the 174 pediatric epidural catheters placed during a 1-year period at
      Children's Hospital of Wisconsin, 59 pediatric patients with chest X-rays
      demonstrating epidural catheter tip on at least 2 days were reviewed. The change
      in epidural catheter position was then calculated. The overall reason for
      discontinuation of epidural analgesia in the larger population was also compiled.
      RESULTS: It was determined that epidural catheters migrated more frequently in
      patients <10 kg and 10-40 kg, when compared to those >40 kg P < 0.001. The
      average migration seen on X-ray was 1.1 levels inward in those <40 kg and 0.3
      levels inward in those >40 kg. The incidence of catheters discontinued secondary
      to falling out, or migrating in, was also increased in those patients <40 kg when
      compared to those >40 kg. CONCLUSION: Results suggest that epidural catheters
      move inward more frequently and fall out more frequently in patients <40 kg.

PMID- 25611613
TI  - Acid-base formalism in dispersion-stabilized S-H...Y (Y?O, S) hydrogen-bonding
      interactions.
AB  - The role of sulfhydryl (S-H) group as hydrogen bond donor is not as well studied
      as that of hydroxyl (O-H). In this work we report on the hydrogen-bonding
      properties of S-H donor in 1:1 complexes of H2S with diethyl ether (Et2O),
      dibutyl ether (Bu2O), and 1,4-dioxane (DO). The complexes were prepared in
      supersonic jet and investigated using infrared predissociation spectroscopy based
      on VUV photoionization detection. The IR spectra of all the complexes showed the
      presence of a broad, intensity-enhanced, and red-shifted hydrogen-bonded S-H
      stretching transition. The S-H stretching frequency was red-shifted by 46, 63,
      and 49 cm(-1) in H2S-Et2O, H2S-Bu2O, and H2S-DO complexes, respectively,
      suggesting that all the complexes are S-H...O bound. Computationally, two
      different S-H...O bound structures, namely, "coplanar" and "perpendicular", were
      obtained as the minimum energy structures for these complexes at the MP2/6
      311++G** level, with the former being the global minimum. However, with Dunning
      type basis sets (aug-cc-pVDZ and aug-cc-pVTZ) only the perpendicular structures
      were found to be stable at the MP2 level. The large widths of the bound S-H
      stretch observed in the experimental spectra (fwhm of 35 to 80 cm(-1)) were
      attributed to inhomogeneous broadening due to multiple conformations of the alkyl
      chains in the coplanar and perpendicular structures populated in the jet. The
      frequency shifts in the hydrogen-bonded S-H stretching mode as well as the bond
      dissociation energies of all S-H...Y (Y?O,S) complexes of H2S, which includes the
      H2S dimer and H2S-methanol (H2S-MeOH) complexes reported in our previous work
      (ChemPhysChem 2013, 14, 905-914), were found to scale linearly with the proton
      affinity of the acceptor molecule. In this regard the S-H group, like O-H, is
      found to conform to the widely accepted acid-base nature of hydrogen-bonding
      interactions. 

PMID- 25611614
TI  - Molecular genetic testing in clinical diagnostic assessments that demonstrate
      correlations in patients with autosomal recessive inherited retinal dystrophy.
AB  - IMPORTANCE: Inherited retinal dystrophies (IRDs) are a group of retinal
      degenerative diseases presenting genetic and clinical heterogeneities, which have
      challenged the genetic and clinical diagnoses of IRDs. Genetic evaluations of
      patients with IRD might result in better clinical assessments and better
      management of patients. OBJECTIVE: To determine the genetic lesions with
      phenotypic correlations in patients with diverse autosomal recessive IRD using
      next-generation sequencing. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 20
      Chinese families affected with autosomal recessive IRD were recruited (with data
      on their detailed family history and on their clinical condition). To identify
      disease-causing mutations in the patients, the targeted sequence capture of IRD
      relevant genes using 2 in-house-designed microarrays, followed by next-generation
      sequencing, was performed. Bioinformatics annotation, intrafamilial cosegregation
      analyses, in silico analyses, and functional analyses were subsequently conducted
      for the variants identified by next-generation sequencing. MAIN OUTCOMES AND
      MEASURES: The results of detailed clinical evaluations, the identification of
      disease-causing mutations, and the clinical diagnosis. RESULTS: Homozygous and
      biallelic variants were identified in 11 of the 20 families (55%) as very likely
      disease-causing mutations, including a total of 17 alleles, of which 12 are
      novel. The 17 alleles identified here include 3 missense, 6 nonsense, 4
      frameshift, and 4 splice site mutations. In addition, we found biallelic RP1
      mutations in a patient with cone-rod dystrophy, which was not previously
      correlated with RP1 mutations. Moreover, the identification of pathogenic
      mutations in 3 families helped to refine their clinical diagnoses. CONCLUSIONS
      AND RELEVANCE: In this study, to our knowledge, many mutations identified in
      those known loci for autosomal recessive IRD are novel. Specific RP1 mutations
      may correlate with cone-rod dystrophy. Genetic evaluations with targeted next
      generation sequencing might result in a better clinical diagnosis and a better
      clinical assessment and, therefore, should be recommended for such patients.

PMID- 25611615
TI  - Stereoselective synthesis of (+)-loline alkaloid skeleton.
AB  - The loline alkaloids present a compact polycyclic pyrrolizidine skeleton and
      contain a strained five-membered ethereal bridge, structural features that have
      proven challenging for synthetic chemists to incorporate since the discovery of
      this natural product family more than 100 years ago. These alkaloids are produced
      by mutualistic fungal symbionts (endophytes) living on certain species of pasture
      grasses and protect the host plant from insect herbivory. The asymmetric total
      synthesis of loline alkaloids is reported and extends our first-generation
      (racemic) synthesis of this alkaloid family. Key to the synthesis is a
      diastereoselective tethered aminohydroxylation of a homoallylic carbamate
      function and a Petasis Borono-Mannich addition. 

PMID- 25611618
TI  - Thermal burn associated with intraoperative convective forced-air warming blanket
      (bair pawsTM flex gown system).
AB  - A 44-year-old man undergoing ambulatory surgery sustained a 5% total body surface
      first-degree burn on his lower and lateral torso and upper thigh during routine
      use of a new forced-air warming Bair PawsTM flex gown system. We describe the
      likely mechanism of injury, intraoperative events suggesting special variation in
      the warming process, and a brief review of adverse events associated with forced
      air warming systems. 

PMID- 25611617
TI  - Increased accumulation of protein-bound N(epsilon)-(carboxymethyl)lysine in
      tissues of healthy rats after chronic oral N(epsilon)-(carboxymethyl)lysine.
AB  - In recent years, chronic diseases related to advanced glycation end products
      (AGEs) have attracted more attention. Because diet is an important exogenous
      source of AGEs, this study aimed to investigate the effects of chronic oral
      administration of pure N(epsilon)-(carboxymethyl)lysine (CML) (a major AGE) at 60
      mg kg(-1) per day on healthy Sprague-Dawley rats. After administration for 12
      weeks, the levels of protein-bound CML were increased to 202 +/- 17, 167 +/- 47,
      217 +/- 44, 107 +/- 4, 144 +/- 23, and 33 +/- 7 MUg/g dry matter in the kidneys,
      heart, liver, lungs, spleen, and pancreas, respectively, in comparison with
      control values of 98 +/- 1, 90 +/- 15, 140 +/- 42, 76 +/- 18, 115 +/- 15, and 30
      +/- 4 MUg/g dry matter. The difference was significant (p < 0.05) for the
      kidneys, heart, liver, and lungs, whereas no significant increase was seen in the
      spleen and pancreas. Furthermore, serum blood urea nitrogen (BUN), creatinine
      (CREA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)
      values increased significantly (p < 0.05), as evidence of impaired kidney and
      liver function. Additionally, the rats' fasting blood glucose (FBG) levels
      remained within the normal range, indicating that chronic intake of CML does not
      promote a rise in blood glucose. These results clearly indicate that a CML-rich
      diet might be a potential health risk in humans, particularly with respect to
      kidney and liver function. 

PMID- 25611616
TI  - Chloroquine and chloroquinoline derivatives as models for the design of
      modulators of amyloid Peptide precursor metabolism.
AB  - The amyloid precursor protein (APP) plays a central role in Alzheimer's disease
      (AD). Preventing deregulated APP processing by inhibiting amyloidogenic
      processing of carboxy-terminal fragments (APP-CTFs), and reducing the toxic
      effect of amyloid beta (Abeta) peptides remain an effective therapeutic strategy.
      We report the design of piperazine-containing compounds derived from chloroquine
      structure and evaluation of their effects on APP metabolism and ability to
      modulate the processing of APP-CTF and the production of Abeta peptide. Compounds
      which retained alkaline properties and high affinity for acidic cell compartments
      were the most effective. The present study demonstrates that (1) the amino side
      chain of chloroquine can be efficiently substituted by a
      bis(alkylamino)piperazine chain, (2) the quinoline nucleus can be replaced by a
      benzyl or a benzimidazole moiety, and (3) pharmacomodulation of the chemical
      structure allows the redirection of APP metabolism toward a decrease of Abeta
      peptide release, and increased stability of APP-CTFs and amyloid intracellular
      fragment. Moreover, the benzimidazole compound 29 increases APP-CTFs in vivo and
      shows promising activity by the oral route. Together, this family of compounds
      retains a lysosomotropic activity which inhibits lysosome-related Abeta
      production, and is likely to be beneficial for therapeutic applications in AD.

PMID- 25611619
TI  - Editorial Comment: Manufacturer's Response to Thermal Burn Associated with
      Intraoperative Convective Forced-Air Warming Blanket (Bair PawsTM Flex Gown
      System).

PMID- 25611620
TI  - Anesthetic management of a patient with arginase deficiency undergoing liver
      transplantation.
AB  - A 20-year-old female underwent orthotopic liver transplantation for arginase
      deficiency, a urea cycle disorder. A hyperammonemic state was prevented by the
      administration of lipid and carbohydrate substrate and avoidance of protein
      loading (including human albumin) and prolonged fasting. Caval cross-clamping may
      have been tolerated poorly owing to the potential interaction between
      hyperargininemia (a nitric oxide precursor) and the lack of collateral venous
      drainage. Ammonia and arginine levels improved in parallel with hepatic function
      after reperfusion of the hepatic graft. 

PMID- 25611621
TI  - Erroneous creation of a surgical airway through the thyrohyoid membrane.
AB  - This case report illustrates the importance of proper assessment, management, and
      creation of an emergent surgical airway. Assessment after the establishment of
      surgical airways should include confirmation of correct surgical site and
      appropriate location and depth of tracheostomy, tracheal tube, or catheter
      placement within the trachea. Supraglottic surgical airway access, as occurred in
      this case, can lead to laryngotracheal and esophageal injury. Early recognition
      and appropriate management of this complication can increase the likelihood of
      preservation of voice and airway function and minimize the extent of esophageal
      injury. 

PMID- 25611622
TI  - Intracranial violation by nasotracheal suction catheter in a patient with a
      history of transsphenoidal surgery.
AB  - A 37-year-old woman underwent transsphenoidal surgery for recurrent pituitary
      adenoma. Postoperatively, she had a prolonged intensive care unit stay and
      repeated tracheal intubations because of inadequate airway reflexes. On
      postoperative day 25, she had difficulty maintaining her airway, and the nursing
      staff attempted orotracheal suctioning, which failed. Nasotracheal suctioning was
      then performed. Her level of consciousness declined, warranting reintubation.
      Computed tomography showed diffuse pneumocephalus and a new parenchymal
      hemorrhage. The only temporally related event was use of a nasotracheal catheter.
      This case suggests that nasotracheal suctioning may not be safe in patients who
      have recently undergone transsphenoidal procedures. 

PMID- 25611624
TI  - Tuning the structural and photophysical properties of cationic Pt(II) complexes
      bearing neutral bis(triazolyl)pyridine ligands.
AB  - The emission properties of a series of cationic Pt(II) complexes bearing neutral
      tridentate 2,6-bis-(1H-1,2,3-triazol-5-yl)pyridine and monoanionic ancillary
      ligands (Cl(-) or CN(-)) are described. By varying the substitution pattern on
      the 1,2,3-triazole moieties of the tridentate luminophore and the nature of the
      ancillary ligand, we were able to tune the intermolecular interactions between
      the complexes and therefore the electronic interactions between the metal
      centers. Indeed, all the compounds possessing Cl(-) as ancillary ligand are
      nonluminescent at room temperature, while the complexes containing CN(-) are
      luminescent. Interestingly, the pi-accepting nature of this ancillary ligand
      induces Pt(II)-Pt(II) interactions irrespectively of bulky substitution patterns
      on the tridentate ligand. 

PMID- 25611623
TI  - Predicting vocabulary growth in children with and without specific language
      impairment: a longitudinal study from 2;6 to 21 years of age.
AB  - PURPOSE: Children with specific language impairment (SLI) often have vocabulary
      impairments. This study evaluates longitudinal growth in a latent trait of
      receptive vocabulary in affected and unaffected children ages 2;6 (years;months)
      to 21 years and evaluates as possible predictors maternal education, child
      gender, and nonverbal IQ. METHOD: A sample of 519 participants (240 with SLI; 279
      unaffected) received an average of 7 annual assessments for a total of 3,012
      latent trait Peabody Picture Vocabulary Test (PPVT) observations. Unconditional
      and conditional multilevel growth models were estimated to evaluate growth
      trajectories and predictor relationships over time. RESULTS: Children with SLI
      had lower levels of receptive vocabulary throughout the age range assessed. They
      did not close the gap with age peers. Children with higher nonverbal IQs had
      better PPVT performance, as did children of mothers with higher education. Child
      gender showed an advantage for young girls that leveled out with age and then
      became an advantage for boys from ages 10 to 21 years. All children's rate of
      vocabulary acquisition slowed around 12 years of age. CONCLUSIONS: The outcomes
      of the study have implications for hypothesized causal pathways for individual
      differences; predictions differ for children under 5 years, 6-10 years, and later
      ages.

PMID- 25611625
TI  - New ansamycin derivatives generated by simultaneous mutasynthesis.
AB  - The conversion from triene- to diene-typed ansamycins is clarified step by step
      in Streptomyces seoulensis IFB-A01. Such an intertype convertibility is adopted
      to establish for the first time the simultaneous mutasynthesis of both types of
      C17-benzene ansamycins (C17BAs). Three of the newly generated unnatural compounds
      showed potent cytotoxicity. 

PMID- 25611626
TI  - Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in
      pregnancy: a randomized controlled trial.

PMID- 25611627
TI  - Odansetron compared with doxylamine and pyridoxine for treatment of nausea in
      pregnancy: a randomized controlled trial.

PMID- 25611628
TI  - In reply.

PMID- 25611629
TI  - Relevance of random biopsy at the transformation zone when colposcopy is
      negative.

PMID- 25611630
TI  - Relevance of random biopsy at the transformation zone when colposcopy is
      negative.

PMID- 25611631
TI  - In reply.

PMID- 25611632
TI  - Exposure to selective serotonin reuptake inhibitors in early pregnancy and the
      risk of miscarriage.

PMID- 25611633
TI  - In reply.

PMID- 25611634
TI  - The maternal early warning criteria: a proposal from the National Partnership for
      Maternal Safety.

PMID- 25611635
TI  - In reply.

PMID- 25611640
TI  - Obstetric Care Consensus No. 2: Levels of maternal care.
AB  - In the 1970s, studies demonstrated that timely access to risk-appropriate
      neonatal and obstetric care could reduce perinatal mortality. Since the
      publication of the Toward Improving the Outcome of Pregnancy report, more than
      three decades ago, the conceptual framework of regionalization of care of the
      woman and the newborn has been gradually separated with recent focus almost
      entirely on the newborn. In this current document, maternal care refers to all
      aspects of antepartum, intrapartum, and postpartum care of the pregnant woman.
      The proposed classification system for levels of maternal care pertains to birth
      centers, basic care (level I), specialty care (level II), subspecialty care
      (level III), and regional perinatal health care centers (level IV). The goal of
      regionalized maternal care is for pregnant women at high risk to receive care in
      facilities that are prepared to provide the required level of specialized care,
      thereby reducing maternal morbidity and mortality in the United States.

PMID- 25611641
TI  - Committee Opinion No. 622: Professional use of digital and social media.
AB  - Digital and social media quickly are becoming universal in modern medical
      practice. Data sharing, online reviews and ratings, and digital privacy concerns
      likely will become a part of most every physician's practice, regardless of his
      or her use of social media. The widespread use of social media in the United
      States brings unprecedented connectivity that opens new horizons for physicians,
      ranging from interactions with patients, to communication with peers and the
      public, to novel approaches to research.

PMID- 25611642
TI  - Committee Opinion No. 623: Emergent therapy for acute-onset, severe hypertension
      during pregnancy and the postpartum period.
AB  - Acute-onset, severe systolic hypertension; severe diastolic hypertension; or both
      can occur in pregnant women or women in the postpartum period. Introducing
      standardized, evidence-based clinical guidelines for the management of patients
      with preeclampsia and eclampsia has been demonstrated to reduce the incidence of
      adverse maternal outcomes. Individuals and institutions should have mechanisms in
      place to initiate the prompt administration of medication when a patient presents
      with a hypertensive emergency. Once the hypertensive emergency is treated, a
      complete and detailed evaluation of maternal and fetal well-being is needed with
      consideration of, among many issues, the need for subsequent pharmacotherapy and
      the appropriate timing of delivery. 

PMID- 25611643
TI  - Committee Opinion No. 624: Cervical cancer screening in low-resource settings.
AB  - Cytology-based cervical cancer screening programs require a number of elements to
      be successful. Certain low-resource settings, like the U.S. Affiliated Pacific
      Islands, lack these elements. Implementing alternative cervical cancer screening
      strategies in low-resource settings can provide consistent, accessible screening
      opportunities. 

PMID- 25611644
TI  - Epidural hematoma with atypical presentation.
AB  - We present a case of massive spinal epidural hematoma with an atypical
      presentation characterized by unilateral, isolated motor deficit in the right
      lower extremity on postoperative day 2 after Collis-Nissen fundoplication and a
      T7-8 epidural for postoperative pain. The epidural had been placed in the
      preoperative theater before surgery. Subcutaneous unfractionated heparin was
      initiated 18 hours later on postoperative day 1 with 3 times daily dosing. The
      patient also received 3 doses of ketorolac starting 10 hours after epidural
      placement. Symptoms were first reported on postoperative day 2, 37 hours after
      epidural placement. Thoracic magnetic resonance imaging showed an epidural
      hematoma extending from T2 through T12, requiring emergent decompression and
      evacuation. The patient made a complete recovery without any resultant neurologic
      deficit. 

PMID- 25611645
TI  - Lagophthalmos after v2 maxillary nerve block.
AB  - We report a previously undescribed complication associated with percutaneous
      maxillary nerve blockade. After the procedure, the patient reported an inability
      to close her ipsilateral eye (lagophthalmos). The patient had received 5 mL of
      0.5% lidocaine for skin anesthesia. After needle placement was confirmed
      fluoroscopically, a combination of 80 mg methylprednisolone (2 mL) and 0.25%
      bupivacaine (3 mL) was administered. Symptoms resolved within 40 minutes. The
      likely cause was local anesthetic effect on the zygomatic branches of the facial
      nerve. When subcutaneous local anesthetic is given for maxillary block, smaller
      volumes should be considered. Doctors and patients should be aware of this
      complication, which may require treatment with artificial tears or patching of
      the eye to prevent corneal injury. 

PMID- 25611646
TI  - Progressive encephalomyelitis with rigidity and myoclonus: anesthesia and glycine
      receptor antibodies.
AB  - Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare
      autoimmune neurological condition. Antibodies targeting glycine receptors (GlyR)
      have been implicated in PERM. Because GlyR activity is enhanced by inhaled
      anesthetic drugs at clinically relevant concentrations, there is a theoretical
      possibility that these drugs may be less effective in the presence of GlyR
      antibodies. We describe a case of general anesthesia in a patient with PERM and
      GlyR antibodies. This patient did not demonstrate a clinically significant
      alteration in the behavioral effects of anesthesia using induction of anesthesia
      with sevoflurane and maintenance of anesthesia using sevoflurane and nitrous
      oxide. 

PMID- 25611648
TI  - Editorial commentary: "progressive encephalomyelitis with rigidity and myoclonus:
      anesthesia and glycine receptor antibodies".

PMID- 25611647
TI  - Total Intravenous Anesthesia Using N-Methyl-D-Aspartate (NMDA) Receptor-Sparing
      Drugs in a Patient with Anti-NMDA Receptor Encephalitis.
AB  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently identified
      syndrome characterized by psychosis and dysautonomia. Treatment includes
      resection of the underlying tumor. While the pathologic mechanism involves
      disruption of NMDA function by anti-NMDA receptor autoantibodies, there are few
      descriptions of the perioperative management or anesthetic approach for such
      patients. We report a classic presentation of anti-NMDA receptor encephalitis and
      describe the use of total IV anesthesia with NMDA receptor-sparing drugs. Modest
      postoperative analgesic requirements, not reported in prior cases, are also
      described in our report. 

PMID- 25611649
TI  - Revealing the real risks of perioperative transfusion: rise of the machines!

PMID- 25611650
TI  - Katz oxygen treatment for catarrh.

PMID- 25611651
TI  - Laughing "Gas" from Knoxville's Dr. H. F. Huffaker.

PMID- 25611652
TI  - Characterizing the epidemiology of postoperative transfusion-related acute lung
      injury.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of
      transfusion-related death in the United States; however, it remains poorly
      characterized in surgical populations. To better inform perioperative transfusion
      practice, and to help mitigate perioperative TRALI, the authors aimed to better
      define its epidemiology before and after TRALI mitigation strategies were
      introduced. METHODS: This retrospective cohort study examined outcomes of adult
      patients undergoing noncardiac surgery with general anesthesia who received
      intraoperative transfusions during 2004 (n = 1,817) and 2011 (n = 1,562). The
      demographics and clinical characteristics of transfusion recipients, blood
      transfusion descriptors, and combined TRALI/possible TRALI incidence rates were
      evaluated. Univariate analyses were used to compare associations between patient
      characteristics, transfusion details, and TRALI mitigation strategies with
      TRALI/possible TRALI incidence rates in a before-and-after study design. RESULTS:
      The incidence of TRALI/possible TRALI was 1.3% (23 of 1,613) in 2004 versus 1.4%
      (22 of 1,562) in 2011 (P = 0.72), with comparable overall rates in males versus
      females (1.4% [23 of 1,613] vs. 1.2% [22 of 1,766]) (P = 0.65). Overall, thoracic
      (3.0% [4 of 133]), vascular (2.7% [10 of 375]), and transplant surgeries (2.2% [4
      of 178]) carried the highest rates of TRALI/possible TRALI. Obstetric and
      gynecologic surgical patients had no TRALI episodes. TRALI/possible TRALI
      incidence increased with larger volumes of blood product transfused (P < 0.001).
      CONCLUSIONS: Perioperative TRALI/possible TRALI is more common than previously
      reported and its risk increases with greater volumes of blood component
      therapies. No significant reduction in the combined incidence of TRALI/possible
      TRALI occurred between 2004 and 2011, despite the introduction of TRALI
      mitigation strategies. Future efforts to identify specific risk factors for
      TRALI/possible TRALI in surgical populations may reduce the burden of this life
      threatening complication.

PMID- 25611653
TI  - Characterizing the epidemiology of perioperative transfusion-associated
      circulatory overload.
AB  - BACKGROUND: Transfusion-associated circulatory overload (TACO) is a leading cause
      of transfusion-related fatalities, but its incidence and associated patient and
      transfusion characteristics are poorly understood. To inform surgical transfusion
      practice and to begin mitigating perioperative TACO, the authors aimed to define
      its epidemiology. METHODS: In this retrospective cohort study, the medical
      records of adult patients undergoing noncardiac surgery with general anesthesia
      during 2004 or 2011 and receiving intraoperative transfusions were screened using
      an electronic algorithm for identification of TACO. Those patients who were
      screened as high probability for TACO underwent rigorous manual review.
      Univariate and multivariate analyses evaluated associations between patient and
      transfusion characteristics with TACO rates in a before-and-after study design.
      RESULTS: A total of 2,162 and 1,908 patients met study criteria for 2004 and
      2011, respectively. The incidence of TACO was 5.5% (119 of 2,162) in 2004 versus
      3.0% (57 of 1,908) in 2011 (P < 0.001), with comparable rates for men (4.8% [98
      of 2,023]) and women (3.8% [78 of 2,047]) (P = 0.09). Overall, vascular (12.1%
      [60 of 497]), transplant (8.8% [17 of 193]), and thoracic surgeries (7.2% [10 of
      138]) carried the highest TACO rates. Obstetric and gynecologic patients had the
      lowest rate (1.4% [4 of 295]). The incidence of TACO increased with volume
      transfused, advancing age, and total intraoperative fluid balance (all P <
      0.001). CONCLUSIONS: The incidence of perioperative TACO is similar to previous
      estimates in nonsurgical populations. There was a reduction in TACO rate between
      2004 and 2011, with incidence patterns remaining comparable in subgroup analyses.
      Future efforts exploring risk factors for TACO may guide preventive or
      therapeutic interventions, helping to further mitigate this transfusion
      complication.

PMID- 25611654
TI  - Figuier's Forlorn Figure: Horace Wells and the "Humbug Affair".

PMID- 25611656
TI  - Is the standard supplied by the association for the advancement of medical
      instrumentation the measure of all things for noninvasive continuous hemodynamic
      devices?

PMID- 25611655
TI  - Assessment of neutrophil gelatinase-associated lipocalin in the brain-dead organ
      donor to predict immediate graft function in kidney recipients: a prospective,
      multicenter study.
AB  - BACKGROUND: Delayed graft function is a major determinant of long-term renal
      allograft survival. Despite considerable efforts to improve donor selection and
      matching, incidence of delayed graft function remains close to 25%. As neutrophil
      gelatinase-associated lipocalin (NGAL) has been shown to predict acute renal
      failure, the authors tested the hypothesis that NGAL measurement in brain-dead
      donors predicts delayed graft function in kidney recipients. METHODS: In a
      prospective, multicenter, observational study, serum NGAL was measured in donors
      at the time of transfer to operating room. The primary endpoint was the delayed
      graft function, defined as the need for renal replacement therapy during the
      first week posttransplantation. RESULTS: Among 159 included brain-dead donors,
      146 were analyzable leading to 243 renal transplantations. Of these, 56 (23%)
      needed renal replacement therapy. Donors' NGAL values were similar in case of
      both delayed and normal graft function in recipients. The area under the receiver
      operating curve for NGAL to predict the need for renal replacement therapy before
      day 8 was 0.50 (95% CI, 0.42 to 0.59). The area under curve for NGAL to predict
      failure to return to a normal graft function at day 8 was 0.51 (95% CI, 0.44 to
      0.59). Using multivariate analysis, NGAL was not associated to the need for renal
      replacement therapy (odds ratio, 0.99; 95% CI, 0.98 to1.00) or failure to return
      to a normal graft function at day 8 (odds ratio, 1.00; 95% CI, 0.99 to 1.00).
      CONCLUSION: NGAL measurement in brain-dead donors at the time of recovery failed
      to predict delayed or normal graft function in kidney recipients.

PMID- 25611657
TI  - In reply.

PMID- 25611658
TI  - Inotrope use in cardiac surgery: a cause of worse outcomes, or just a marker of
      patients who are at risk?

PMID- 25611659
TI  - In reply.

PMID- 25611660
TI  - Lung ultrasonography for the detection of anesthesia-induced lung atelectasis.

PMID- 25611661
TI  - In reply.

PMID- 25611662
TI  - Early childhood anesthetic neurotoxicity and unmeasured covariates: there's the
      RUB.

PMID- 25611664
TI  - Old guidelines or methods cannot insure quality or progress.

PMID- 25611663
TI  - In reply.

PMID- 25611665
TI  - In reply.

PMID- 25611666
TI  - In reply.

PMID- 25611672
TI  - Perioperative transfusion: a complicated story.

PMID- 25611673
TI  - Regioselective palladium-catalyzed decarboxylative cross-coupling reaction of
      alkenyl acids with coumarins: synthesis of 3-styrylcoumarin compounds.
AB  - A novel and efficient protocol for the regioselective synthesis of 3
      styrylcoumarins from readily available cinnamic acids and coumarins is presented.
      The reaction proceeds via a decarboxylative cross-coupling mediated by a
      catalytic amount of Pd(OAc)2, with Ag2CO3 as an oxidant, and with 1,10
      phenanthroline as a ligand. A plausible reaction mechanism for this process is
      depicted, and the resulting 3-styrylcoumarins show excellent fluorescence quantum
      yields. 

PMID- 25611674
TI  - Modeling nanomaterial environmental fate in aquatic systems.
AB  - Mathematical models improve our fundamental understanding of the environmental
      behavior, fate, and transport of engineered nanomaterials (NMs, chemical
      substances or materials roughly 1-100 nm in size) and facilitate risk assessment
      and management activities. Although today's large-scale environmental fate models
      for NMs are a considerable improvement over early efforts, a gap still remains
      between the experimental research performed to date on the environmental fate of
      NMs and its incorporation into models. This article provides an introduction to
      the current state of the science in modeling the fate and behavior of NMs in
      aquatic environments. We address the strengths and weaknesses of existing fate
      models, identify the challenges facing researchers in developing and validating
      these models, and offer a perspective on how these challenges can be addressed
      through the combined efforts of modelers and experimentalists. 

PMID- 25611675
TI  - Influence of packing density and surface roughness of vertically-aligned carbon
      nanotubes on adhesive properties of gecko-inspired mimetics.
AB  - We have systematically studied the macroscopic adhesive properties of vertically
      aligned nanotube arrays with various packing density and roughness. Using a
      tensile setup in shear and normal adhesion, we find that there exists a maximum
      packing density for nanotube arrays to have adhesive properties. Too highly
      packed tubes do not offer intertube space for tube bending and side-wall contact
      to surfaces, thus exhibiting no adhesive properties. Likewise, we also show that
      the surface roughness of the arrays strongly influences the adhesion properties
      and the reusability of the tubes. Increasing the surface roughness of the array
      strengthens the adhesion in the normal direction, but weakens it in the shear
      direction. Altogether, these results allow progress toward mimicking the gecko's
      vertical mobility. 

PMID- 25611676
TI  - DNA bases assembled on the Au(110)/electrolyte interface: a combined experimental
      and theoretical study.
AB  - Among the low-index single-crystal gold surfaces, the Au(110) surface is the most
      active toward molecular adsorption and the one with fewest electrochemical
      adsorption data reported. Cyclic voltammetry (CV), electrochemically controlled
      scanning tunneling microscopy (EC-STM), and density functional theory (DFT)
      calculations have been employed in the present study to address the adsorption of
      the four nucleobases adenine (A), cytosine (C), guanine (G), and thymine (T), on
      the Au(110)-electrode surface. Au(110) undergoes reconstruction to the (1 * 3)
      surface in electrochemical environment, accompanied by a pair of strong
      voltammetry peaks in the double-layer region in acid solutions. Adsorption of the
      DNA bases gives featureless voltammograms with lower double-layer capacitance,
      suggesting that all the bases are chemisorbed on the Au(110) surface. Further
      investigation of the surface structures of the adlayers of the four DNA bases by
      EC-STM disclosed lifting of the Au(110) reconstruction, specific molecular
      packing in dense monolayers, and pH dependence of the A and G adsorption. DFT
      computations based on a cluster model for the Au(110) surface were performed to
      investigate the adsorption energy and geometry of the DNA bases in different
      adsorbate orientations. The optimized geometry is further used to compute models
      for STM images which are compared with the recorded STM images. This has provided
      insight into the physical nature of the adsorption. The specific orientations of
      A, C, G, and T on Au(110) and the nature of the physical adsorbate/surface
      interaction based on the combination of the experimental and theoretical studies
      are proposed, and differences from nucleobase adsorption on Au(111)- and Au(100)
      electrode surfaces are discussed. 

PMID- 25611677
TI  - Facile synthesis of zwitterionic polymer-coated core-shell magnetic nanoparticles
      for highly specific capture of N-linked glycopeptides.
AB  - Highly selective and efficient capture of glycosylated proteins and peptides from
      complex biological samples is of profound significance for the discovery of
      disease biomarkers in biological systems. Recently, hydrophilic interaction
      liquid chromatography (HILIC)-based functional materials have been extensively
      utilized for glycopeptide enrichment. However, the low amount of immobilized
      hydrophilic groups on the affinity material has limited its specificity,
      detection sensitivity and binding capacity in the capture of glycopeptides.
      Herein, a novel affinity material was synthesized to improve the binding capacity
      and detection sensitivity for glycopeptides by coating a poly(2
      (methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide (PMSA) shell
      onto Fe3O4@SiO2 nanoparticles, taking advantage of reflux-precipitation
      polymerization for the first time (denoted as Fe3O4@SiO2@PMSA). The thick polymer
      shell endows the nanoparticles with excellent hydrophilic property and several
      functional groups on the polymer chains. The resulting Fe3O4@SiO2@PMSA
      demonstrated an outstanding ability for glycopeptide enrichment with high
      selectivity, extremely high detection sensitivity (0.1 fmol), large binding
      capacity (100 mg g(-1)), high enrichment recovery (above 73.6%) and rapid
      magnetic separation. Furthermore, in the analysis of real complicated biological
      samples, 905 unique N-glycosylation sites from 458 N-glycosylated proteins were
      reliably identified in three replicate analyses of a 65 MUg protein sample
      extracted from mouse liver, showing the great potential of Fe3O4@SiO2@PMSA in the
      detection and identification of low-abundance N-linked glycopeptides in
      biological samples. 

PMID- 25611679
TI  - Antithrombin or thrombomodulin administration in severe pneumonia patients with
      sepsis and disseminated intravascular coagulation: comment on two papers.

PMID- 25611680
TI  - Preparation of octahydro- and tetrahydro-[1,10]phenanthroline zirconium and
      hafnium complexes for olefin polymerization.
AB  - Post-metallocenes were constructed for olefin polymerization using
      1,2,3,4,7,8,9,10-octahydro[1,10]phenanthroline and 1,2,3,4
      tetrahydro[1,10]phenanthroline derivatives. A series of zirconium complexes -
      LZrCl2(NHMe2)2 [L = 2,9-H2-C12H12N2 (4), 2,9-Me2-C12H12N2 (5), 2,9-nBu2-C12H12N2
      (6), and 2,9-iPr2-C12H12N2 (7)] - and hafnium complexes - LHfCl2(NHMe2)2 [L = 2,9
      H2-C12H12N2 (8), 2,9-Me2-C12H12N2 (9), 2,9-nBu2-C12H12N2 (10), and 2,9-iPr2
      C12H12N2 (11)] - were synthesized via the reaction of
      octahydro[1,10]phenanthrolines (2,9-R2-C12H12(NH)2) with (Me2N)2MCl2 (DME). The
      reaction of 2,9-R2-C12H12(NH)2 with (PhCH2)2ZrCl2 in the presence of a small
      amount of THF afforded a series of THF adduct analogs, i.e., LZrCl2(THF)2 [L =
      2,9-H2-C12H12N2 (12), 2,9-Me2-C12H12N2 (13), 2,9-nBu2-C12H12N2 (14), and 2,9-iPr2
      C12H12N2 (15)]. The treatment of 12 and 13 with excess Me3Al resulted in the
      formation of unexpected complexes, i.e., (eta(4)-LAlMe2)ZrCl2(Me) [L = 2,9-H2
      C12H12N2 (16) and 2,9-Me2-C12H12N2 (17)], in which the Me2Al unit forms a five
      membered ring through binding with the two nitrogen donors and the MeCl2Zr unit
      slips to an eta(4)-binding mode containing the N-C-C-N fragment. The treatment of
      tetrahydro[1,10]phenanthrolines [2,9-R2-C12NH9(NH)] with M(CH2Ph)4 afforded
      tribenzyl zirconium complexes LZr(CH2Ph)3 - [L = 2,9-Me2-C12NH9N (18) and 2,9
      nBu2-C12NH9N (19)] - and hafnium complexes - LHf(CH2Ph)3 [L = 2,9-Me2-C12NH9N
      (20), 2,9-nBu2-C12NH9N (21), and 2,9-iPr2-C12NH9N (22)]. The structures of 4, 5,
      12, 17, and 22 were elucidated by X-ray crystallography. The newly prepared
      complexes were screened for ethylene/1-octene copolymerization activity: 12 and
      16 were potent catalysts (activities of 74 * 10(6) g mol-Zr h(-1) at ~120 
      degrees C under 30 bar ethylene) for the production of wax-like low-molecular
      weight polyethylene (Mn: ~5000), which is widely used in industry.

PMID- 25611678
TI  - Clinical significance of estrogen receptor beta in breast and prostate cancer
      from biological aspects.
AB  - Breast and prostate cancers are among the most common of all cancers. They are
      referred to as hormone-dependent cancers, because estrogen and androgen are
      involved in their development and growth. The effects of these hormones are
      mediated by their respective receptors, estrogen receptor (ER) alpha and androgen
      receptor. Around 18 years ago, a second ER, ERbeta, which has a very similar
      structure to ERalpha, was discovered. Its function has been investigated using a
      variety of methods and biological systems, leading to our present understanding
      that ERbeta can interact with or inhibit ERalpha and androgen receptor function
      directly and/or indirectly, suppress cell growth, and influence responsiveness to
      endocrine therapy. In order to apply the "inhibition of cell growth" function to
      cancer treatment, several specific ERbeta agonists have been synthesized and are
      being tested for effectiveness in cancer treatment. We need to keep our eyes on
      ERbeta. 

PMID- 25611681
TI  - Running-Intensity Fluctuations in Elite Rugby Sevens Performance.
AB  - PURPOSE: To investigate temporal variation in running intensity across and within
      halves and evaluate the agreement between match-analysis indices used to identify
      fluctuations in running intensity in rugby sevens. METHODS: Data from a 15-Hz
      global positioning system (GPS) were collected from 12 elite rugby sevens players
      during the IRB World Sevens Series (N = 21 full games). Kinematic (eg, relative
      distance [RD]) and energetic (eg, metabolic power [MP]) match-analysis indices
      were determined from velocity-time curves and used to investigate between-halves
      variations. Mean MP and RD were used to identify peak 2-minute periods of play.
      Adjacent 2-minute periods (prepeak and postpeak) were compared with peak periods
      to identify changes in intensity. MP and RD were expressed relative to maximal
      oxygen uptake (VO2max) and speed at VO2max, respectively, and compared in their
      ability to describe the intensity of peak periods and their temporal occurrence.
      RESULTS: Small to moderate reductions were present for kinematic (RD; 8.9%) and
      energetic (MP; 6%) indices between halves. Peak periods (RD = 130 m/min, MP =13
      W/kg) were higher (P < .001) than the match average (RD = 94 m/min, MP = 9.5
      W/kg) and the prepeak and postpeak periods (P < .001). RD underestimated the
      intensity of peak periods compared with MP (bias 16%, limits of agreement [LoA]
      +/- 6%). Peak periods identified by RD and MP were temporally dissociated (bias
      21 s, LoA +/- 212 s). CONCLUSIONS: The findings suggest that running intensity
      varies between and within halves; however, the index used will influence both the
      magnitude and the temporal identification of peak periods.

PMID- 25611682
TI  - Native like helices in a specially designed beta peptide in the gas phase.
AB  - In the natural peptides, helices are stabilized by hydrogen bonds that point
      backward along the sequence direction. Until now, there is only little evidence
      for the existence of analogous structures in oligomers of conformationally
      unrestricted beta amino acids. We specifically designed the beta peptide Ac
      (beta(2)hAla)6-LysH(+) to form native like helical structures in the gas phase.
      The design follows the known properties of the peptide Ac-Ala6-LysH(+) that forms
      a alpha helix in isolation. We perform ion-mobility mass-spectrometry and
      vibrational spectroscopy in the gas phase, combined with state-of-the-art density
      functional theory simulations of these molecular systems in order to characterize
      their structure. We can show that the straightforward exchange of alanine
      residues for the homologous beta amino acids generates a system that is generally
      capable of adopting native like helices with backward oriented H-bonds. By
      pushing the limits of theory and experiments, we show that one cannot assign a
      single preferred structure type due to the densely populated energy landscape and
      present an interpretation of the data that suggests an equilibrium of three
      helical structures. 

PMID- 25611683
TI  - Modulation of calmodulin lobes by different targets: an allosteric model with
      hemiconcerted conformational transitions.
AB  - Calmodulin is a calcium-binding protein ubiquitous in eukaryotic cells, involved
      in numerous calcium-regulated biological phenomena, such as synaptic plasticity,
      muscle contraction, cell cycle, and circadian rhythms. It exibits a
      characteristic dumbell shape, with two globular domains (N- and C-terminal lobe)
      joined by a linker region. Each lobe can take alternative conformations, affected
      by the binding of calcium and target proteins. Calmodulin displays considerable
      functional flexibility due to its capability to bind different targets, often in
      a tissue-specific fashion. In various specific physiological environments (e.g.
      skeletal muscle, neuron dendritic spines) several targets compete for the same
      calmodulin pool, regulating its availability and affinity for calcium. In this
      work, we sought to understand the general principles underlying calmodulin
      modulation by different target proteins, and to account for simultaneous effects
      of multiple competing targets, thus enabling a more realistic simulation of
      calmodulin-dependent pathways. We built a mechanistic allosteric model of
      calmodulin, based on an hemiconcerted framework: each calmodulin lobe can exist
      in two conformations in thermodynamic equilibrium, with different affinities for
      calcium and different affinities for each target. Each lobe was allowed to switch
      conformation on its own. The model was parameterised and validated against
      experimental data from the literature. In spite of its simplicity, a two-state
      allosteric model was able to satisfactorily represent several sets of
      experiments, in particular the binding of calcium on intact and truncated
      calmodulin and the effect of different skMLCK peptides on calmodulin's saturation
      curve. The model can also be readily extended to include multiple targets. We
      show that some targets stabilise the low calcium affinity T state while others
      stabilise the high affinity R state. Most of the effects produced by calmodulin
      targets can be explained as modulation of a pre-existing dynamic equilibrium
      between different conformations of calmodulin's lobes, in agreement with linkage
      theory and MWC-type models. 

PMID- 25611684
TI  - Do Mediterranean-type ecosystems have a common history?--insights from the
      Buckthorn family (Rhamnaceae).
AB  - Mediterranean-type ecosystems (MTEs) are remarkable in their species richness and
      endemism, but the processes that have led to this diversity remain enigmatic.
      Here, we hypothesize that continent-dependent speciation and extinction rates
      have led to disparity in diversity between the five MTEs of the world: the Cape,
      California, Mediterranean Basin, Chile, and Western Australia. To test this
      hypothesis, we built a phylogenetic tree for 280 Rhamnaceae species, estimated
      divergence times using eight fossil calibrations, and used Bayesian methods and
      simulations to test for differences in diversification rates. Rhamnaceae lineages
      in MTEs generally show higher diversification rates than elsewhere, but
      speciation and extinction dynamics show a pattern of continent-dependence. We
      detected high speciation and extinction rates in California and significantly
      lower extinction rates in the Cape and Western Australia. The independent
      colonization of four of five MTEs may have occurred conterminously in the
      Oligocene/Early Miocene, but colonization of the Mediterranean Basin happened
      later, in the Late Miocene. This suggests that the in situ radiations of these
      clades were initiated before the onset of winter rainfall in these regions. These
      results indicate independent evolutionary histories of Rhamnaceae in MTEs,
      possibly related to the intensity of climate oscillations and the geological
      history of the regions. 

PMID- 25611686
TI  - Do high-fidelity training models translate into better skill acquisition for an
      endourologist?
AB  - PURPOSE OF REVIEW: Nowadays, accessibility to the operative room is becoming more
      limited for medical students and residents, principally due to decreasing
      operative time, increasing waiting list, ethical consideration and legal issue in
      case of any complications. Simulation models have gained in popularity and are
      now considered a major component in the training and skill development of medical
      students and residents before coming to the operative room. In this review, we
      summarized and discussed the relevant aspect of ureteroscopy training models and
      gave an overview of the advantage in skill acquisition while training with a high
      fidelity model. RECENT FINDINGS: Currently, there is an increase in surgical
      programs trying to implement endourology training models into the curriculum. The
      training simulators that would allow the medical students and residents to
      rapidly reach an autonomous level are yet to be developed. Several ureteroscopy
      models have been described and validated; however, the transposition of skill
      acquisition into real-life surgery is not properly demonstrated. SUMMARY:
      Training reduces the learning curve for novice medical students or residents.
      However, further studies are still needed to better define the impact of skill
      acquisition in real life and its sustainability.

PMID- 25611685
TI  - Results of clinical genetic testing of 2,912 probands with hypertrophic
      cardiomyopathy: expanded panels offer limited additional sensitivity.
AB  - PURPOSE: Hypertrophic cardiomyopathy (HCM) is caused primarily by pathogenic
      variants in genes encoding sarcomere proteins. We report genetic testing results
      for HCM in 2,912 unrelated individuals with nonsyndromic presentations from a
      broad referral population over 10 years. METHODS: Genetic testing was performed
      by Sanger sequencing for 10 genes from 2004 to 2007, by HCM CardioChip for 11
      genes from 2007 to 2011 and by next-generation sequencing for 18, 46, or 51 genes
      from 2011 onward. RESULTS: The detection rate is ~32% among unselected probands,
      with inconclusive results in an additional 15%. Detection rates were not
      significantly different between adult and pediatric probands but were higher in
      females compared with males. An expanded gene panel encompassing more than 50
      genes identified only a very small number of additional pathogenic variants
      beyond those identifiable in our original panels, which examined 11 genes.
      Familial genetic testing in at-risk family members eliminated the need for
      longitudinal cardiac evaluations in 691 individuals. Based on the projected costs
      derived from Medicare fee schedules for the recommended clinical evaluations of
      HCM family members by the American College of Cardiology Foundation/American
      Heart Association, our data indicate that genetic testing resulted in a minimum
      cost savings of about $0.7 million. CONCLUSION: Clinical HCM genetic testing
      provides a definitive molecular diagnosis for many patients and provides cost
      savings to families. Expanded gene panels have not substantively increased the
      clinical sensitivity of HCM testing, suggesting major additional causes of HCM
      still remain to be identified.

PMID- 25611687
TI  - A Critical Evaluation on a Fulbright Experience.
AB  - PROBLEM: Although many Fulbright awardees have detailed experiences in varied
      countries, there is less discussion on the impact on the host institution and
      efforts to sustain the change between both participants. METHODS: The critical
      evaluation examines professional and personal impact of a Fulbright U.S. Scholar
      Award at the University of Johannesburg in South Africa. FINDINGS: This work
      details the influence of the host faculty in the experience for both the host
      faculty in the Department of Nursing and the scholar receiving the awarded.
      Challenges to achieve a successful exchange are described, and activities to
      sustain connections and maximize impact are presented, with particular emphasis
      on midwifery. CONCLUSIONS: Collaborative research and teaching activities
      strengthened through administrative endorsement support ongoing exchange.

PMID- 25611689
TI  - MicroRNA-155 deficiency attenuates ischemia-reperfusion injury after liver
      transplantation in mice.
AB  - Liver ischemia-reperfusion injury (IRI) is a major cause of morbidity and
      mortality after resection surgery, liver transplantation, and hemorrhagic and
      septic shock. Mir-155 is upregulated by a broad range of inflammatory mediators,
      and it has been demonstrated to be involved in both innate and adaptive immune
      responses. However, the role of mir-155 in liver IRI has never been investigated.
      In this study, mir-155 deficiency protected mice from liver IRI, as shown by
      lower serum alanine aminotransferase (ALT) levels and Suzuki scores. Mir-155
      deficiency results in the development of M2 macrophages, which respond to IR
      induced innate immune stimulation by producing a regulatory inflammatory response
      with higher level of IL-10, but lower levels of TNF-alpha, IL-6, and IL-12p40.
      Mir-155 deficiency suppresses IL-17 expression, which contributes to the liver
      IRI development. In our further in vitro study, the results show that the Th17
      differentiation is inhibited by SOCS1 overexpression and the promoted M2
      macrophage development induced by mir-155 deficiency is abolished by SOCS1
      knockdown. In conclusion, mir-155 deficiency attenuates liver IRI through
      upregulation of SOCS1, and this was associated with promoted M2 macrophage and
      inhibited Th17 differentiation.

PMID- 25611688
TI  - Attitudes and perceptions of urban African Americans of a "dirty bomb"
      radiological terror event: results of a qualitative study and implications for
      effective risk communication.
AB  - OBJECTIVES: Radiological terror presents a real threat, but little is known about
      how low-income, urban African Americans may respond to such threats. The aim of
      this study was to understand the unique challenges of this group and to explore
      their knowledge of what a "dirty bomb" is, their intended behaviors should one
      occur, and their barriers to complying with "shelter in place" recommendations.
      METHODS: Thirty-seven 18-65-year-olds who were users of community centers in
      disadvantaged areas participated in 3 focus groups in Philadelphia. Results were
      analyzed by using the Krueger method of analyzing narrative text. RESULTS: The
      responses highlighted little knowledge or concern about a dirty bomb. Lack of
      trust in local authorities was expressed, with participants indicating that they
      did not feel their needs were addressed. While shelter in place was understood,
      most said they would still check on family or talk with others to get the "whole
      truth" because the most trusted information sources were neighbors and community
      leaders. CONCLUSION: Our results indicate that a risk communication intervention
      for urban minorities may support desirable behaviors in the event of a dirty
      bomb, but successful communication will require establishing a local leader as a
      spokesperson to convince people of the importance of sheltering in place.

PMID- 25611690
TI  - A molecular view of DNA-conjugated nanoparticle association energies.
AB  - Nanoparticles functionalized with short sequences of DNA represent a promising
      platform for customizable self assembly. Though much recent research has focused
      on the phase behavior and assembly of these structures, little has been done to
      precisely characterize the pairwise interaction between particles. Here we
      present a detailed calculation of the association between DNA-nanoparticle
      conjugates using 3SPN.2, a coarse-grained model of DNA that accounts for
      molecular structure and base-pairing. We compare our results to those obtained
      experimentally using MUm sized particles and analyze the free energy surfaces
      that characterize interparticle hybridization. Next, we study the importance of
      three-body effects and their impact on particle association and melting. Lastly,
      we explore the observation by Park et al. [Nature, 451, 553 (2008)] that DNA
      nanoparticle crystallization can be inhibited by the deletion of a single
      nucleotide. Using our model, we suggest that the role of this nucleotide is to
      disrupt frustration. 

PMID- 25611693
TI  - Can 2015 be a transformative year for diagnostics in wound care?

PMID- 25611692
TI  - Peroxisome proliferator-activated receptor-gamma agonist pioglitazone ameliorates
      white matter lesion and cognitive impairment in hypertensive rats.
AB  - AIMS: Cerebrovascular white matter lesion (WML) is a major subtype of cerebral
      small vessel disease. Clinical drugs are not available for WML. We investigated
      whether peroxisome proliferator-activated receptor-gamma agonist pioglitazone,
      with properties of vascular protection and antiinflammation, exerts beneficial
      effect in hypertensive WML rats. METHODS: Stroke-prone renovascular hypertensive
      rats (RHRSP) were treated with pioglitazone for 12 weeks. Morris water maze
      experiment was conducted to assess cognition. WML was observed by Luxol fast blue
      staining. Smooth muscle actin-alpha, collagen I, collagen IV, glial fibrillary
      acidic protein, and ionized calcium-binding adaptor molecule-1 were evaluated by
      immunohistochemistry. Interleukin-1 beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha) in brain and soluble intercellular adhesion molecule-1 (sICAM
      1) in serum were detected. RESULTS: Pioglitazone significantly attenuated WML in
      corpus callosum, caudate putamen, external capsule, and internal capsule.
      Cognitive impairment in RHRSP was ameliorated by pioglitazone. Pioglitazone
      attenuated arteriolar remodeling and reduced sICAM-1 level in serum. Pioglitazone
      decreased the proliferation of microglia and astrocyte and lowered the expression
      of proinflammatory cytokines IL-1beta and TNF-alpha in the white matter.
      CONCLUSIONS: Long-term treatment of pioglitazone has beneficial effect on
      hypertension-induced WML and cognition decline, which may partly through its
      effect on attenuation of arteriolar remodeling, endothelial activation, and brain
      inflammation.

PMID- 25611694
TI  - Automated wound assessment system calculates 3D dimensions on a mobile device.

PMID- 25611696
TI  - Impaired induction of interleukin 28B and expression of interferon lambda 4
      associated with nonresponse to interferon-based therapy in chronic hepatitis C.
AB  - BACKGROUND AND AIM: Interferon (IFN) lambda plays an important role in innate
      immunity to protect against hepatitis C viral (HCV) infection. Single nucleotide
      polymorphisms (SNPs) near IL28B (IFNlambda3) are strongly associated with
      treatment response to IFNalpha therapy in chronic hepatitis C (CHC) patients.
      Recently, IFNlambda4 related to IL28B-unfavorable allele was discovered. However,
      the impact of IFNlambdas on CHC is unknown. We aimed to investigate the mechanism
      underlying responsiveness to IFN-based therapy in CHC associated with SNPs near
      IL28B. METHODS: We evaluated the basal mRNA levels and ex-vivo induction of
      IFNlambda expression including IFNlambda4 in peripheral blood mononuclear cells
      (PBMCs) from 50 CHC patients treated with pegylated-IFNalpha/RBV. Furthermore, we
      investigated the effect of IFNlambda4 on induction of IL28B in vitro. RESULTS:
      When PBMCs were stimulated with IFNalpha and polyinosinic-polycytidylic acid,
      IL28B induction was significantly lower in patients with IL28B-unfavorable
      genotype (rs12979860 CT/TT) than those with IL28B-favorable genotype (rs12979860
      CC; P=0.049). IL28B induction was lower in nonresponders than in relapsers (P =
      0.04), and it was also lower in nonsustained virological responder patients for
      triple therapy including NS3 protease inhibitors. IFNlambda4 mRNA was detected in
      12 of 26 patients with IL28B-unfavorable SNP, and IFNlambda4 expression was
      associated with lower IL28B induction in patients with IL28B-unfavorable genotype
      (P=0.04) and nonresponse to IFNalpha therapy (P=0.003). Overexpression of
      IFNlambda4 suppressed IL28B induction and promoter activation. CONCLUSIONS:
      Impaired induction of IL28B, related to IFNlambda4 expression in PBMCs of IL28B
      unfavorable patients, is associated with nonresponse to IFNalpha-based therapy
      for hepatitis C viral infection.

PMID- 25611697
TI  - Echo Doppler Estimation of Pulmonary Capillary Wedge Pressure in Patients with
      Severe Aortic Stenosis.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become a treatment
      option for patients with severe aortic stenosis (AS) and high surgical risk.
      Assessment of symptoms in these patients is challenging because of advanced age,
      comorbidities, and limited physical activity. Noninvasive quantification of
      pulmonary capillary wedge pressure (PCWP) in candidates for TAVR may be helpful
      for risk stratification. The objective of the study was to create a model for
      estimation of PCWP by echo Doppler in patients with severe AS. METHODS AND
      RESULTS: Data from 80 patients with severe AS referred for TAVR were used to
      develop an echo Doppler model for predicting PCWP. Its performance was evaluated
      in the test cohort of 33 patients who had invasive and noninvasive evaluation. No
      single echo Doppler parameter estimated PCWP accurately. In the retrospective
      analysis, the multilinear regression provided an accurate estimate of PCWP (r(2)
      = 0.74). The model included, in order of importance (all P < 0.05), the ratio of
      early transmitral velocity (E) to annular velocity (E'), the left ventricular
      ejection fraction, and the velocity time integral of tricuspid regurgitation
      signal. In the prospective cohort of patients with severe AS, the model
      demonstrated good predictive ability of PCWP (r = 0.77, P < 0.01). CONCLUSION: In
      patients with severe AS, noninvasive estimation of PCWP is possible by
      integration of two-dimensional, spectral, and tissue Doppler variables.

PMID- 25611698
TI  - The Association Between Hospital Readmission and Pulmonologist Follow-up Visits
      in Patients With COPD.
AB  - BACKGROUND: The high frequency of readmissions in patients with COPD remains a
      significant problem. The impact of a pulmonologist follow-up visit during the
      month after discharge from hospital because of COPD exacerbation on reducing
      readmissions was examined. A profile of patients who did not attend the follow-up
      visits was built. METHODS: Our population-based retrospective cohort study
      analyzed the data of all patients with COPD who were treated at a lung institute
      in an Israeli hospital and were hospitalized between January 1, 2004, and
      December 31, 2010. Multivariate logistic regression was used to characterize the
      patient who did not attend the follow-up visit and to examine the effect of lack
      of visit on rehospitalization within 90 days of discharge. Cox proportional
      hazards analysis was used to model the effect of lacking visit on additional
      hospitalization or death during the study period. RESULTS: Of the 195 patients
      enrolled in the study, 44.1% had follow-up visits with pulmonologists within 30
      days of discharge. Not attending the follow-up visit was associated with distant
      residence, a higher number of hospitalizations in the previous year, a lack of a
      recommendation in the discharge letter for a follow-up visit, and a lower
      frequency of follow-up visits with pulmonologists in the previous year. Moreover,
      not attending the follow-up visit was associated with a significant increased
      risk of rehospitalization within 90 days of discharge (OR, 2.91; 95% CI, 1.06
      8.01). CONCLUSIONS: Early follow-up visits with pulmonologists seem to reduce the
      exacerbation-related rehospitalization rates of patients with COPD. We recommend
      that patients have early postdischarge follow-up visits with pulmonologists.

PMID- 25611699
TI  - Down regulation of miR-202 modulates Mxd1 and Sin3A repressor complexes to induce
      apoptosis of pancreatic cancer cells.
AB  - Aberrant regulation of microRNA expression in pancreatic cancers has been shown
      to play an important role in its inherent poor prognosis and malignant potential.
      MicroRNAs have also been shown to inhibit translation of genes by targeting the
      3'-untranslated region (3-UTR) of mRNAs resulting in the inhibition of
      translation and often destruction of the mRNA. In the present study we
      investigated the role of the microRNA miR-202 in the apoptotic pathways of
      pancreatic cancer cells. The adamantyl-related molecule, 3-Cl-AHPC down-regulated
      expression of miR-202 and miR-578 resulting in the increased expression of mRNA
      and protein expression of their target genes, Max dimerization protein 1
      (Mxd1/Mad1) and the Sin3A associated protein 18 (SAP18). Overexpression of pre
      miR-202 led to diminished levels of Mxd1 and blocked the 3-Cl-AHPC-mediated
      increase in Mxd1 mRNA expression. The addition of the microRNA inhibitor 2'-O
      methylated miR-202 enhanced the 3-Cl-AHPC-mediated increase of Mxd1 mRNA levels
      as well as 3-CI-AHPC-mediated apoptosis. We found increased Mxd1 bound to the
      Sin3A repressor protein complex through its increased binding with HDAC-2 and
      subsequently enhanced transcriptional repression in cells as evidenced by
      increased HDAC activity. Mxd1 also repressed human telomerase reverse
      transcriptase (hTERT) mRNA expression through its increased binding to the hTERT
      promoter site and resulted in decreased telomerase activity in cells. Our results
      demonstrate that down regulation of miR-202 increased the expression of its
      target Mxd1, followed by Mxd1 recruitment to the Sin3A repressor complex and
      through its dimerization with Max, and increased repression of Myc-Max target
      proteins.

PMID- 25611700
TI  - The preparation of ethylenediamine-modified fluorescent carbon dots and their use
      in imaging of cells.
AB  - In this work, fluorescent carbon dots (CDs) were synthesized using a hydrothermal
      method with glucose as the carbon source and were surface-modified with
      ethylenediamine. The properties of as-prepared CDs were analyzed by transmission
      electron microscopy (TEM), Fourier transform infrared (FTIR), ultraviolet-visible
      light (UV/vis) absorption and fluorescent spectra. Furthermore, CDs conjugated
      with mouse anti-(human carcinoembryonic antigen) (CEA) monoclonal antibody were
      successful employed in the biolabeling and fluorescent imaging of human gastric
      carcinoma cells. In addition, the cytotoxicity of CDs was also tested using human
      gastric carcinoma cells. There was no apparent cytotoxicity on human gastric
      carcinoma cells. These results suggest the potential application of the as
      prepared CDs in bioimaging and related fields.

PMID- 25611701
TI  - The role of stromal fibroblasts in lung carcinogenesis: A target for
      chemoprevention?
AB  - The tumour microenvironment plays an essential role in the development and spread
      of cancers. Tumour cells interact with the surrounding extracellular matrix
      (ECM), embedded within which, are a variety of non-cancer cells including cells
      of the vasculature, immune system and fibroblasts. The essential role of
      fibroblasts in the cultivation and maintenance of an environment in which tumour
      cells are able to maintain their aggressive phenotypic traits is becoming
      increasingly well documented. Cancer-associated fibroblasts are able to secrete a
      vast array of ECM-modulating factors, meaning that they have potential for a
      functional role in every step of the carcinogenic process. In particular, they
      are likely to have a role in early tumour-initiating inflammatory events, and so
      may provide a potential target for chemopreventive intervention. This review
      summarises the known interactions between lung tumour cells and surrounding
      reactive fibroblasts, highlighting the need to further investigate cancer
      associated fibroblasts as therapeutic targets in lung cancer chemoprevention
      strategies. 

PMID- 25611702
TI  - Variations of depression treatment among women with hypertension.
AB  - The objective was to examine depression treatment among non-pregnant women, aged
      22 and older, with hypertension, utilizing cross-sectional data from the 2006 and
      2007 Medical Expenditure Panel Survey. Depression treatment patterns by
      demographic, socioeconomic, health care access, and health characteristics were
      analyzed utilizing chi-square tests and logistic and multinomial logistic
      regressions. Overall, 23.9% had no depression treatment, 56.8% had antidepressant
      use only, and 19.3% had psychotherapy with or without antidepressants. African
      Americans (adjusted odds ratio [AOR] = 0.47), Latinas (AOR = 0.46), and uninsured
      women (AOR = 0.39) were significantly less likely to report any treatment for
      depression compared with Whites and those with private insurance. 

PMID- 25611704
TI  - Aviation and technology in diabetes management.

PMID- 25611705
TI  - Analysis of leaf surfaces using scanning ion conductance microscopy.
AB  - Leaf surfaces are highly complex functional systems with well defined chemistry
      and structure dictating the barrier and transport properties of the leaf cuticle.
      It is a significant imaging challenge to analyse the very thin and often complex
      wax-like leaf cuticle morphology in their natural state. Scanning electron
      microscopy (SEM) and to a lesser extent Atomic force microscopy are techniques
      that have been used to study the leaf surface but their remains information that
      is difficult to obtain via these approaches. SEM is able to produce highly
      detailed and high-resolution images needed to study leaf structures at the
      submicron level. It typically operates in a vacuum or low pressure environment
      and as a consequence is generally unable to deal with the in situ analysis of
      dynamic surface events at submicron scales. Atomic force microscopy also possess
      the high-resolution imaging required and can follow dynamic events in ambient and
      liquid environments, but can over exaggerate small features and cannot image most
      leaf surfaces due to their inherent roughness at the micron scale. Scanning ion
      conductance microscopy (SICM), which operates in a liquid environment, provides a
      potential complementary analytical approach able to address these issues and
      which is yet to be explored for studying leaf surfaces. Here we illustrate the
      potential of SICM on various leaf surfaces and compare the data to SEM and atomic
      force microscopy images on the same samples. In achieving successful imaging we
      also show that SICM can be used to study the wetting of hydrophobic surfaces in
      situ. This has potentially wider implications than the study of leaves alone as
      surface wetting phenomena are important in a range of fundamental and applied
      studies. 

PMID- 25611706
TI  - Optimal Time for IUD Insertion After an STI.

PMID- 25611707
TI  - Considerations for identifying ectopic pregnancy.

PMID- 25611703
TI  - Molecular and cellular pathogenesis of adamantinomatous craniopharyngioma.
AB  - Adamantinomatous craniopharyngiomas (ACPs) are the most common pituitary tumours
      in children. Although histologically benign, these are clinically aggressive
      tumours, difficult to manage and associated with poor quality of life for the
      patients. Several human and mouse studies have provided unequivocal evidence that
      the over-activation of the WNT/beta-catenin signalling pathway underlies the
      molecular aetiology of these tumours. Recently, research using genetically
      modified mouse models of human ACP have revealed a critical and unexpected non
      cell autonomous role for pituitary stem cells in ACP tumourigenesis, which has
      expanded the cancer stem cell paradigm. As the result of this basic research, the
      pathogenesis of ACP is being unveiled, with promising implications for the
      development of novel treatments against these childhood neoplasms. These benign
      tumours may additionally represent a unique model to provide insights into the
      initial steps of oncogenesis. 

PMID- 25611709
TI  - How should we manage incidentalomas?

PMID- 25611710
TI  - Optimal Duration of Treatment Regimens for H. pylori Eradication.

PMID- 25611711
TI  - Common questions about the diagnosis and management of benign prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common condition that increases in
      prevalence with age. A history should include onset, duration, and severity of
      lower urinary tract symptoms and medication use to rule out other causes of
      symptoms. Physical examination includes a digital rectal examination and
      assessment for bladder distention or neurologic impairment. Recommended tests
      include serum prostate-specific antigen measurement and urinalysis to help
      identify infection, genitourinary cancer, or calculi as an alternative cause of
      lower urinary tract symptoms. BPH severity is assessed using validated, self
      administered symptom questionnaires such as the American Urological Association
      Symptom Index or International Prostate Symptom Score. Mild or nonbothersome
      symptoms do not require treatment. Bothersome symptoms are managed with lifestyle
      modifications, medications, and surgery. Alpha blockers are first-line
      medications for BPH. Surgical referral is indicated if BPH-related complications
      develop, medical therapy fails, or the patient chooses it. Dietary supplements,
      such as saw palmetto, pygeum, cernilton, and beta sitosterols, and acupuncture
      are not recommended for the management of BPH. 

PMID- 25611712
TI  - Schizophrenia.
AB  - Schizophrenia is the most common psychotic disease, with a global prevalence of
      less than 1%. It affects all ethnicities and is slightly more common in men.
      Patients with schizophrenia commonly experience debilitating social and
      occupational impairments, but some are able to function well with proper
      treatment. Symptom onset is generally between late adolescence and the mid-30s.
      There are two categories of symptoms: positive and negative. Hallucinations,
      delusions, and disorganized speech are examples of positive symptoms, whereas
      decreased emotional expression and lack of motivation are negative symptoms.
      Antipsychotic medications can treat some symptoms of schizophrenia but are
      associated with multiple adverse effects, including extrapyramidal symptoms and
      metabolic changes. Patients receiving antipsychotic medications, especially
      second-generation (or atypical) antipsychotics, should be monitored regularly for
      metabolic changes and cardiovascular risk factors. Persons with schizophrenia who
      undergo psychosocial therapy in addition to medical therapy have better outcomes.
      Patients diagnosed with schizophrenia have a higher overall mortality rate than
      the general public, partly because of the increased suicide risk associated with
      schizophrenia. 

PMID- 25611713
TI  - Incidentalomas: initial management.
AB  - Incidentalomas are increasingly common findings on radiologic studies, causing
      worry for physicians and patients. Physicians should consider the risk of
      discovering incidentalomas when contemplating imaging. Patients may assume that
      incidentalomas are cancer, and may not be aware of the radiation risks associated
      with repeat imaging. Once incidentalomas are detected, appropriate management is
      dependent on an informed patient's wishes and the clinical situation. Guidelines
      are provided for the initial management of eight incidentalomas (pituitary,
      thyroid, pulmonary, hepatic, pancreatic, adrenal, renal, and ovarian). Patients
      presenting with pituitary incidentalomas should undergo pituitary-specific
      magnetic resonance imaging if the lesion is 1 cm or larger, or if it abuts the
      optic chiasm. Thyroid incidentalomas are ubiquitous, but nodules larger than 1 to
      2 cm are of greater concern. Worrisome pulmonary incidentalomas are those larger
      than 8 mm or those with irregular borders, eccentric calcifications, or low
      density. However, current guidelines recommend that even pulmonary incidentalomas
      as small as 4 mm be followed. Solid hepatic incidentalomas 5 mm or larger should
      be monitored closely, and multiphasic scanning is helpful. Pancreatic cystic
      neoplasms have malignant potential, and surgery is recommended for pancreatic
      cysts larger than 3 cm with suspicious features. Adrenal lesions larger than 4 cm
      are usually biopsied. The Bosniak classification is a well-accepted means of
      triaging renal incidentalomas. Lesions at category IIF or greater require serial
      monitoring or surgery. Benign or probably benign ovarian cysts 3 cm or smaller in
      premenopausal women or 1 cm or smaller in postmenopausal women do not require
      follow-up. Ovarian cysts with thickened walls or septa, or solid components with
      blood flow, should be managed closely. 

PMID- 25611714
TI  - Accounting for complexity: aligning current payment models with the breadth of
      care by different specialties.

PMID- 25611715
TI  - Painless vision loss.

PMID- 25611716
TI  - Group medical visits for chronic diseases.

PMID- 25611723
TI  - Information from Your Family Doctor. Incidentalomas.

PMID- 25611724
TI  - Information from Your Family Doctor. Schizophrenia.

PMID- 25611725
TI  - Transposable elements as agents of rapid adaptation may explain the genetic
      paradox of invasive species.
AB  - Rapid adaptation of invasive species to novel habitats has puzzled evolutionary
      biologists for decades, especially as this often occurs in the face of limited
      genetic variability. Although some ecological traits common to invasive species
      have been identified, little is known about the possible genomic/genetic
      mechanisms that may underlie their success. A common scenario in many
      introductions is that small founder population sizes will often lead to reduced
      genetic diversity, but that invading populations experience large environmental
      perturbations, such as changes in habitat and environmental stress. Although
      sudden and intense stress is usually considered in a negative context, these
      perturbations may actually facilitate rapid adaptation by affecting genome
      structure, organization and function via interactions with transposable elements
      (TEs), especially in populations with low genetic diversity. Stress-induced
      changes in TE activity can alter gene action and can promote structural variation
      that may facilitate the rapid adaptation observed in new environments. We focus
      here on the adaptive potential of TEs in relation to invasive species and
      highlight their role as powerful mutational forces that can rapidly create
      genetic diversity. We hypothesize that activity of transposable elements can
      explain rapid adaptation despite low genetic variation (the genetic paradox of
      invasive species), and provide a framework under which this hypothesis can be
      tested using recently developed and emerging genomic technologies.

PMID- 25611726
TI  - Diffusion-weighted imaging: Effects of intravascular contrast agents on apparent
      diffusion coefficient measures of breast malignancies at 3 Tesla.
AB  - BACKGROUND: To determine whether apparent diffusion coefficient (ADC) measures of
      breast lesions at 3 Tesla (T) are affected by gadolinium administration. METHODS:
      The study included 19 patients who underwent 3T MRI. Diffusion-weighted imaging
      (DWI) was acquired with b = 0, 100, and 800 s/mm(2) before and after a dynamic
      contrast-enhanced (DCE) sequence. ADC values were measured for each lesion and
      normal fibroglandular tissue. Pre- and postcontrast ADC measures were compared by
      Wilcoxon signed-rank test, and differences between groups were compared by Mann
      Whitney U test; P < 0.05 was considered statistically significant. RESULTS: There
      was no significant difference in pre- and postcontrast ADC measured at b = 0,
      100, 800 s/mm(2) for malignancies (median change: -0.4%, -0.01 * 10(-3) mm(2) /s,
      P = 0.40), but there was a slight increase in postcontrast ADC in normal tissue
      (+1.6%, +0.04 * 10(-3) mm(2) /s, P = 0.0006). Findings were similar for both
      lesions (-0.4%, -0.01 * 10(-3) mm(2) /s, P = 0.54) and normal tissue (+1.5%,
      +0.03 * 10(-3) mm(2) /s, P = 0.002) with ADC measured at b = 0,800 and also at b
      = 100, 800 s/mm(2) (lesions: +0.9%, +0.01 * 10(-3) mm(2) /s, P = 0.71; normal
      tissue: +1.8%, +0.03 * 10(-3) mm(2) /s, P = 0.005). For lesions, results were not
      affected by lesion size, type (mass versus nonmass enhancement), mean initial
      enhancement, late enhancement, or delayed enhancement rate on DCE-MRI (P > 0.05
      for all). Normal tissue showed some trends with greater progressive enhancement
      rates and higher late enhancement levels correlating with greater increase in
      postcontrast ADC (P = 0.09 for both). CONCLUSION: Our results show that breast
      lesion ADC measures using our approach were not significantly altered following
      DCE-MRI at 3T, suggesting DWI and DCE-MRI can be performed in any order without
      affecting diagnostic criteria. However, influences of contrast on ADC measures in
      normal breast tissue were observed and require further investigation.

PMID- 25611727
TI  - Bariatric surgery and diabetes: Implications of type 1 versus insulin-requiring
      type 2.
AB  - OBJECTIVE: To report the impact of bariatric surgery on metabolic outcomes in
      patients with type 1 diabetes (DM1) versus insulin-requiring type 2 diabetes
      mellitus (IRDM2). METHODS: Ten subjects with DM1 were compared with 118 subjects
      with IRDM2 at baseline and at 1 and 2 years post-bariatric surgery for:
      anthropometric measures, HbA1c, and number of medications (anti-hyperglycemic,
      anti-hypertensive, lipid-lowering). RESULTS: DM1 and IRDM2 groups lost similar
      amounts of weight 2 years post-bariatric surgery (39.5 +/- 14.7 kg vs. 40.3 +/-
      24.4 kg). IRDM2 subjects had significant improvements in HbA1c (7.8% +/- 1.4% vs.
      6.8% +/- 1.4%, P value <0.0001) and decreases in number of anti-hyperglycemic
      (2.4 +/- 0.8 vs. 0.7 +/- 0.8, P value <0.0001), anti-hypertensive (2.2 +/- 1.3
      vs. 1.3 +/- 1.2, P value <0.0001), and lipid-lowering (1.1 +/- 0.8 vs. 0.6 +/-
      0.6, P value <0.0001) medications. DM1 subjects had no improvement in HbA1c (8.2%
      +/- 1.6% vs. 7.8% +/- 0.9%) or use of anti-hypertensive medications (2.1 +/- 1.4
      vs. 2.3 +/- 1.5). Their use of lipid-lowering medications improved (1.0 +/- 0.5
      vs. 0.5 +/- 0.8, P value 0.04). CONCLUSIONS: Our study suggests that improved
      glycemic control may not be an expected outcome when considering bariatric
      surgery in patients with DM1; however, additional investigation is warranted.

PMID- 25611728
TI  - The many glia of a tiny nematode: studying glial diversity using Caenorhabditis
      elegans.
AB  - Glia constitute a major, understudied population of cells in the nervous system.
      Currently, it is appreciated that these cells exhibit vast morphological,
      functional, and molecular diversity, but our understanding of glial biology is
      limited. Some key unanswered questions include how glial diversity is generated
      during development and what functions distinct glial subtypes serve in the mature
      nervous system. The nematode Caenorhabditis elegans contains a defined set of
      glia, which have clear morphological and molecular differences, and thus provides
      a simplified model for understanding glial diversity. In addition, recent
      experiments suggest that the molecular mechanisms underlying the generation of
      glial diversity in C. elegans are conserved with those in mammals. In this
      review, we summarize the surprising diversity of glial subtypes present in this
      simple organism, and highlight current thinking about what roles they perform in
      the nervous system. We emphasize how genetic approaches may be used to identify
      the mechanistic origins of glial diversity, which is key to understanding how
      glia function in health and disease. 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- 25611729
TI  - Randomized trial of peginterferon alpha-2b plus low and escalating dose of
      ribavirin in patients with chronic hepatitis C with high viral load genotype 1.
AB  - It has been reported that elderly patients with chronic hepatitis C infection
      cannot tolerate standard combination therapy. In this randomized, controlled
      trial, the efficacy and safety of peginterferon alpha-2b plus a low and
      escalating dose of ribavirin in chronic hepatitis C patients with high viral load
      genotype 1 were investigated. Sixty-two patients were randomized into combination
      therapy with standard ribavirin dosing (group 1) or low and escalating ribavirin
      dosing (group 2). Patients were evaluated for safety and efficacy of treatment.
      There was no significant difference in the prevalence of virological response
      between the groups throughout the treatment as well as 24 weeks after treatment.
      However, the response in patients >=60 years of age was higher in group 1 than in
      group 2 at early treatment phase (P = 0.015). The prevalence of completion of
      therapy in patients >=60 years of age tended to be higher in group 2 than in
      group 1 (50% vs. 0%, P = 0.055). There was no significant difference in dose
      modification of peginterferon alpha-2b between the groups. However, dose
      modification of ribavirin was significantly more frequent in group 1 than in
      group 2 (60% vs. 24%, P = 0.005). These data suggest that combination therapy
      with low and escalating dosing of ribavirin may be safer in elderly patients than
      that with standard dosing of ribavirin without impairing the treatment response.

PMID- 25611730
TI  - A neuroinformatics study to compare inhibition efficiency of three natural
      ligands (Fawcettimine, Cernuine and Lycodine) against human brain
      acetylcholinesterase.
AB  - Enzyme-inhibition is considered as a potent therapeutic approach to the treatment
      of diseases associated with acetylcholinesterase (AChE). The present study
      elucidates molecular interactions of human brain AChE, with three natural ligands
      Lycodine, Cernuine and Fawcettimine for comparison. Docking between these ligands
      and enzyme was performed using 'Autodock 4.2'. It was determined that polar and
      hydrophobic interactions play an important role in the correct positioning of
      Lycodine, Cernuine and Fawcettimine within the 'catalytic site' of AChE to permit
      docking. This approach would be helpful to understand the selectivity of the
      given drug molecule in the treatment of neurological disorder. Moreover, the
      present study confirms that Lycodine is a more efficient inhibitor of human brain
      AChE compared to Cernuine and Fawcettimine with reference to DeltaG and Ki
      values. 

PMID- 25611731
TI  - In vivo biocompatibility of boron doped and nitrogen included conductive-diamond
      for use in medical implants.
AB  - Recently, there has been interest in investigating diamond as a material for use
      in biomedical implants. Diamond can be rendered electrically conducting by doping
      with boron or nitrogen. This has led to inclusion of boron doped and nitrogen
      included diamond elements as electrodes and/or feedthroughs for medical implants.
      As these conductive device elements are not encapsulated, there is a need to
      establish their clinical safety for use in implants. This article compares the
      biocompatibility of electrically conducting boron doped diamond (BDD) and
      nitrogen included diamond films and electrically insulating poly crystalline
      diamond films against a silicone negative control and a BDD sample treated with
      stannous octoate as a positive control. Samples were surgically implanted into
      the back muscle of a guinea pig for a period of 4-15 weeks, excised and the
      implant site sectioned and submitted for histological analysis. All forms of
      diamond exhibited a similar or lower thickness of fibrotic tissue encapsulating
      compared to the silicone negative control samples. All forms of diamond exhibited
      similar or lower levels of acute, chronic inflammatory, and foreign body
      responses compared to the silicone negative control indicating that the materials
      are well tolerated in vivo.

PMID- 25611732
TI  - Oxide-supported IrNiO(x) core-shell particles as efficient, cost-effective, and
      stable catalysts for electrochemical water splitting.
AB  - Active and highly stable oxide-supported IrNiO(x) core-shell catalysts for
      electrochemical water splitting are presented. IrNi(x)@IrO(x) nanoparticles
      supported on high-surface-area mesoporous antimony-doped tin oxide (IrNiO(x)/Meso
      ATO) were synthesized from bimetallic IrNi(x) precursor alloys (PA-IrNi(x) /Meso
      ATO) using electrochemical Ni leaching and concomitant Ir oxidation. Special
      emphasis was placed on Ni/NiO surface segregation under thermal treatment of the
      PA-IrNi(x)/Meso-ATO as well as on the surface chemical state of the
      particle/oxide support interface. Combining a wide array of characterization
      methods, we uncovered the detrimental effect of segregated NiO phases on the
      water splitting activity of core-shell particles. The core-shell IrNiO(x)/Meso
      ATO catalyst displayed high water-splitting activity and unprecedented stability
      in acidic electrolyte providing substantial progress in the development of PEM
      electrolyzer anode catalysts with drastically reduced Ir loading and
      significantly enhanced durability.

PMID- 25611733
TI  - The extracellular RNA complement of Escherichia coli.
AB  - The secretion of biomolecules into the extracellular milieu is a common and well
      conserved phenomenon in biology. In bacteria, secreted biomolecules are not only
      involved in intra-species communication but they also play roles in inter-kingdom
      exchanges and pathogenicity. To date, released products, such as small molecules,
      DNA, peptides, and proteins, have been well studied in bacteria. However, the
      bacterial extracellular RNA complement has so far not been comprehensively
      characterized. Here, we have analyzed, using a combination of physical
      characterization and high-throughput sequencing, the extracellular RNA complement
      of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric
      Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have
      compared it to its intracellular RNA complement. Our results demonstrate that a
      large part of the extracellular RNA complement is in the size range between 15
      and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore,
      RNA is associated with OMVs and the relative abundances of RNA biotypes in the
      intracellular, OMV and OMV-free fractions are distinct. Apart from rRNA
      fragments, a significant portion of the extracellular RNA complement is composed
      of specific cleavage products of functionally important structural noncoding
      RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the
      extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic,
      and coding regions, of which some are so far uncharacterised, for example,
      transcripts mapping to the fimA-fimL and ves-spy intergenic regions. Our study
      provides the first detailed characterization of the extracellular RNA complement
      of the enteric model bacterium E. coli. Analogous to findings in eukaryotes, our
      results suggest the selective export of specific RNA biotypes by E. coli, which
      in turn indicates a potential role for extracellular bacterial RNAs in
      intercellular communication.

PMID- 25611735
TI  - Herniated Lumbar Disks: Real-time MR Imaging Evaluation during Continuous
      Traction.
AB  - PURPOSE: To assess the morphologic changes in herniated lumbar intervertebral
      disks and surrounding structures during lumbar traction by using real-time
      magnetic resonance (MR) imaging. MATERIALS AND METHODS: This prospective study
      was approved by the institutional review board, and written informed consent was
      obtained from all participants. Forty-eight consecutive patients with lumbar disk
      herniation (13 men and 35 women) were treated with continuous lumbar traction by
      using a nonmagnetic traction device. Real-time MR imaging of the lumbar spine was
      performed before the initiation of traction and at 10-minute intervals during 30
      minutes of 30 kg of continuous traction. Sagittal and axial MR images were
      analyzed to determine qualitative changes during lumbar traction. Quantitative
      changes caused by traction on the lumbar spine were determined by measurement of
      lumbar vertebral column elongation and the disk reduction ratio. RESULTS:
      Continuous traction on herniated lumbar disks and surrounding structures resulted
      in change in disk shape, disk reduction with opening in the intervertebral disk,
      reduction of herniated disk volume, separation of the disk and adjoining nerve
      root, and widening of the facet joint. Both the mean lumbar vertebral column
      length (elongation of 1.45% after 30 minutes, P < .001) and the mean disk
      reduction ratio (8.57%, 15.24%, and 17.94% after 10, 20, and 30 minutes of
      traction, respectively) increased with time of traction. CONCLUSION: The results
      of this study demonstrated that the real-time effects of continuous traction on
      herniated lumbar intervertebral disks and their surrounding structures can be
      visualized by using MR imaging.

PMID- 25611734
TI  - Leaf and stem economics spectra drive diversity of functional plant traits in a
      dynamic global vegetation model.
AB  - Functional diversity is critical for ecosystem dynamics, stability and
      productivity. However, dynamic global vegetation models (DGVMs) which are
      increasingly used to simulate ecosystem functions under global change, condense
      functional diversity to plant functional types (PFTs) with constant parameters.
      Here, we develop an individual- and trait-based version of the DGVM LPJmL (Lund
      Potsdam-Jena managed Land) called LPJmL- flexible individual traits (LPJmL-FIT)
      with flexible individual traits) which we apply to generate plant trait maps for
      the Amazon basin. LPJmL-FIT incorporates empirical ranges of five traits of
      tropical trees extracted from the TRY global plant trait database, namely
      specific leaf area (SLA), leaf longevity (LL), leaf nitrogen content (Narea ),
      the maximum carboxylation rate of Rubisco per leaf area (vcmaxarea), and wood
      density (WD). To scale the individual growth performance of trees, the leaf
      traits are linked by trade-offs based on the leaf economics spectrum, whereas
      wood density is linked to tree mortality. No preselection of growth strategies is
      taking place, because individuals with unique trait combinations are uniformly
      distributed at tree establishment. We validate the modeled trait distributions by
      empirical trait data and the modeled biomass by a remote sensing product along a
      climatic gradient. Including trait variability and trade-offs successfully
      predicts natural trait distributions and achieves a more realistic representation
      of functional diversity at the local to regional scale. As sites of high climatic
      variability, the fringes of the Amazon promote trait divergence and the
      coexistence of multiple tree growth strategies, while lower plant trait diversity
      is found in the species-rich center of the region with relatively low climatic
      variability. LPJmL-FIT enables to test hypotheses on the effects of functional
      biodiversity on ecosystem functioning and to apply the DGVM to current challenges
      in ecosystem management from local to global scales, that is, deforestation and
      climate change effects.

PMID- 25611736
TI  - Pseudoprogression in Patients with Glioblastoma: Assessment by Using Volume
      weighted Voxel-based Multiparametric Clustering of MR Imaging Data in an
      Independent Test Set.
AB  - PURPOSE: To validate a volume-weighted voxel-based multiparametric clustering
      (VVMC) method for magnetic resonance imaging data that is designed to
      differentiate between pseudoprogression and early tumor progression (ETP) in
      patients with glioblastoma in an independent test set. MATERIALS AND METHODS:
      This retrospective study was approved by the local institutional review board,
      with waiver of the need to obtain informed consent. The study patients were
      grouped chronologically into a training set (108 patients) and a test set (54
      patients). The reference standard was pathologic findings or subsequent clinical
      radiologic study results. By using the optimal cutoff determined in the training
      set, the diagnostic performance of VVMC was subsequently tested in the test set
      and was compared with that of single-parameter measurements (apparent diffusion
      coefficient [ADC], normalized cerebral blood volume [nCBV], and initial area
      under the time-signal intensity curve). RESULTS: Interreader agreement was
      highest for VVMC (intraclass correlation coefficient, 0.87-0.89). Receiver
      operating characteristic curve analysis revealed that VVMC performed the best as
      a classifier, although statistical significance was not demonstrated with respect
      to the nCBV in the training set. In the test set, the diagnostic accuracy of VVMC
      was higher than that of any single-parameter measurements, but this trend reached
      significance only for the ADC. When the entire population was considered, VVMC
      had significantly better diagnostic accuracy than did any single parameter (P =
      .003-.046 for reader 1; P = .002-.016 for reader 2). Results of fivefold cross
      validation confirmed the trends in both the training set and the test set.
      CONCLUSION: VVMC is a superior and more reproducible imaging biomarker than
      single-parameter measurements for differentiating between pseudoprogression and
      ETP in patients with glioblastoma. Online supplemental material is available for
      this article.

PMID- 25611737
TI  - Hereditary Spastic Paraplegia: Beyond Clinical Phenotypes toward a Unified
      Pattern of Central Nervous System Damage.
AB  - PURPOSE: To investigate whether specific patterns of brain gray matter (GM)
      regional volumes and white matter (WM) microstructural abnormalities and spinal
      cord atrophy occur in patients with pure and complicated hereditary spastic
      paraplegias (HSPs). Relationships between clinical and cognitive features of
      patients with HSP who had brain and cervical cord damage were also investigated.
      MATERIALS AND METHODS: This study was approved by the local ethical committees on
      human studies, and written informed consent from all subjects was obtained prior
      to enrollment. Forty-four patients with HSP (20 genetically defined cases and 24
      without genetic diagnosis) and 19 healthy control subjects underwent clinical,
      neuropsychological, and advanced magnetic resonance (MR) imaging evaluations.
      Patterns of GM atrophy and WM microstructural damage obtained by using structural
      and diffusion-tensor MR imaging were compared between groups. Cervical cord
      atrophy was also assessed by using an active surface method. Correlations between
      clinical, cognitive, and diffusion-tensor MR imaging measures were evaluated.
      RESULTS: Clinical data showed that spastic paraplegia is accompanied by a number
      of other features, including sensory disturbances, and verbal and spatial memory
      deficits, not only in complicated HSP but also in pure HSP. MR imaging
      demonstrated a similar involvement of motor, association, and cerebellar WM
      pathways (P < .05, family-wise error corrected for multiple comparisons) and
      cervical cord (P < .001) in patients with HSP relative to healthy control
      subjects, regardless of their clinical picture. The severity of WM damage
      correlated with the degree of spasticity (P < .05, family-wise error corrected)
      and cognitive impairment (r values, -0.39 to 0.51; P values, .001-.05) in both
      pure and complicated HSP. CONCLUSION: The detection of a distributed pattern of
      central nervous system damage in patients with pure and complicated HSP suggests
      that the "primary" corticospinal tract involvement known to occur in these
      patients may be associated with a neurodegenerative process, which spreads out to
      extramotor regions, likely via anatomic connections. This observation is in line
      with emerging pieces of evidence that, independent of the clinical phenotype,
      there is a common neurodegenerative cascade shared by different neurologic
      disorders.

PMID- 25611739
TI  - Reply: To PMID 24942697.

PMID- 25611738
TI  - Specificity and dynamics of effector and memory CD8 T cell responses in human
      tick-borne encephalitis virus infection.
AB  - Tick-borne encephalitis virus (TBEV) is transferred to humans by ticks. The virus
      causes tick-borne encephalitis (TBE) with symptoms such as meningitis and
      meningoencephalitis. About one third of the patients suffer from long-lasting
      sequelae after clearance of the infection. Studies of the immune response during
      TBEV-infection are essential to the understanding of host responses to TBEV
      infection and for the development of therapeutics. Here, we studied in detail the
      primary CD8 T cell response to TBEV in patients with acute TBE. Peripheral blood
      CD8 T cells mounted a considerable response to TBEV-infection as assessed by Ki67
      and CD38 co-expression. These activated cells showed a CD45RA-CCR7-CD127-
      phenotype at day 7 after hospitalization, phenotypically defining them as
      effector cells. An immunodominant HLA-A2-restricted TBEV epitope was identified
      and utilized to study the characteristics and temporal dynamics of the antigen
      specific response. The functional profile of TBEV-specific CD8 T cells was
      dominated by variants of mono-functional cells as the effector response matured.
      Antigen-specific CD8 T cells predominantly displayed a distinct Eomes+Ki67+T-bet+
      effector phenotype at the peak of the response, which transitioned to an Eomes
      Ki67-T-bet+ phenotype as the infection resolved and memory was established. These
      transcription factors thus characterize and discriminate stages of the antigen
      specific T cell response during acute TBEV-infection. Altogether, CD8 T cells
      responded strongly to acute TBEV infection and passed through an effector phase,
      prior to gradual differentiation into memory cells with distinct transcription
      factor expression-patterns throughout the different phases. 

PMID- 25611740
TI  - The Effectiveness of a Functional Knee Brace on Joint-Position Sense in Anterior
      Cruciate Ligament-Reconstructed Individuals.
AB  - It is estimated that approximately 350,000 individuals undergo anterior cruciate
      ligament (ACL) reconstruction surgery in each year in the US. Although ACL
      reconstruction surgery and postoperative rehabilitation are successfully
      completed, deficits in postural control remain prevalent in ACL-reconstructed
      individuals. In order to assist the lack of balance ability and reduce the risk
      of retear of the reconstructed ACL, physicians often provide a functional knee
      brace on the patients' return to physical activity. However, it is not known
      whether use of the functional knee brace enhances knee-joint position sense in
      individuals with ACL reconstruction. Thus, the effect of a functional knee brace
      on knee-joint position sense in an ACL-reconstructed population needs be
      critically appraised. After systematically review of previously published
      literature, 3 studies that investigated the effect of a functional knee brace in
      ACL-reconstructed individuals using joint-position-sense measures were found.
      They were rated as level 2b evidence in the Centre of Evidence Based Medicine
      Level of Evidence chart. Synthesis of the reviewed studies indicated inconsistent
      evidence of a functional knee brace on joint-position improvement after ACL
      reconstruction. More research is needed to provide sufficient evidence on the
      effect of a functional knee brace on joint-position sense after ACL
      reconstruction. Future studies need to measure joint-position sense in closed
      kinetic-chain fashion since ACL injury usually occurs under weight-bearing
      conditions. 

PMID- 25611742
TI  - Successful rescue thrombolysis in massive pulmonary embolism with intracerebral
      hemorrhage.
AB  - We report the case of a man with a massive pulmonary embolism, which lead to
      cardiac arrest. After ruptured aneurysm clipping, he was successfully treated by
      rescue thrombolysis administered as compassionate treatment despite the risk of
      cerebral bleeding. The patient was discharged from the intensive care unit; his
      initial neurological, cardiac, and pulmonary conditions restored. In case of life
      threatening pulmonary embolism, the risk-benefit ratio of thrombolysis therapy
      should be systematically evaluated and the decision adapted to each patient. 

PMID- 25611741
TI  - Evaluation of a HIV voluntary opt-out screening program in a Singapore hospital.
AB  - BACKGROUND: Early diagnosis of human immunodeficiency virus (HIV) allows for
      appropriately timed interventions with improved outcomes, but HIV screening among
      asymptomatic persons and the general population in Singapore remains low. In
      2008, Singapore's Ministry of Health implemented HIV voluntary opt-out screening
      (VOS) for hospitalised adults. We evaluated the outcome of VOS and surveyed
      reasons for its low uptake in our institution. METHODS: We assessed the outcomes
      of the VOS programme from January 2010 to December 2013 at National University
      Hospital, a 1081-bed tertiary hospital in Singapore. We also examined reasons for
      opting-in and opting-out using an interviewer-administered structured
      questionnaire in a representative sample in January 2013. RESULTS: 107,523
      patients fulfilled VOS criteria and were offered HIV screening, of which 5215
      (4.9%) agreed to testing. 4850 (93.1%) of those who opted-in had an HIV test
      done. Three (0.06%) tested positive for HIV. 238 patients (14.2%) were surveyed
      regarding reasons for opting-in or out of VOS. 21 (8.8%) had opted-in. Patients
      who opted-in were likely to be younger, more educated and reported having more
      regular sexual partners. Type of housing, number of casual sexual partners,
      sexual orientation, intravenous drug use, condom use and previous sexually
      transmitted infection were not associated with deciding to opt-in/out. Patients'
      most common reasons for opting-out were: belief that they were at low risk
      (50.2%), belief that they were too old (26.8%), cost (6.9%) and aversion to
      venepuncture (6.5%). The most common reason for opting-in was desire to know
      their HIV status (47.6%). CONCLUSION: The success of an HIV-VOS program is
      largely determined by test uptake. Our study showed that the majority of eligible
      VOS patients opted-out of HIV screening. Given the considerable cost and low
      yield of this programme, more needs to be done to better equip patients in self
      risk assessment and opting in to testing.

PMID- 25611743
TI  - Arytenoid cartilage dislocation after laparoscopic surgery for treatment of
      diabetes.
AB  - I report the occurrence of left arytenoid dislocation in 2 patients undergoing
      laparoscopic surgical procedures formerly used only for weight loss and that are
      now being used for treatment of diabetes. After uncomplicated tracheal
      intubation, a calibrating orogastric tube was inserted into the esophagus blindly
      and without difficulty. On the second postoperative day, both patients complained
      of severe hoarseness, for which arytenoid dislocation was diagnosed. I suspect
      that the insertion of the calibrating orogastric tube in these nonobese patients
      may have led to the development of this rare complication. Recognition of its
      occurrence and subsequent treatment are important to preventing long-term
      consequences of arytenoid dislocation. 

PMID- 25611744
TI  - Failure of lung isolation by a double-lumen endotracheal tube rescued by the
      concomitant use of an arndt bronchial blocker under direct visualization.
AB  - Failure of a double-lumen endotracheal tube (DLT) to isolate the lung during
      thoracic surgery can have significant consequences. In this report, we examine an
      approach for rescuing a malpositioned DLT. A 37F left-sided DLT was inserted and
      its proper position confirmed. After positioning, repeat confirmation of position
      and the ability to achieve 1-lung ventilation were performed, but inadequate
      isolation of the lung being operated on was noted after incision. A 7-Fr Arndt
      bronchial blocker was positioned through the tracheal lumen of the DLT to obtain
      1-lung ventilation. This technique can be used to rescue a malfunctioning DLT
      without the need for extubating and reintubating the trachea. 

PMID- 25611745
TI  - Thoracoscopic wedge resection of the lung using high-frequency jet ventilation in
      a postpneumonectomy patient.
AB  - A 61-year-old female ex-smoker presented with a suspicious right lower lobe mass
      after previously undergoing a left pneumonectomy. Due to the peripheral nature of
      the lung lesion, a right thoracoscopic wedge resection was proposed by the
      surgical team. Adequate ventilation, oxygenation, and surgical conditions were
      obtained using high-frequency jet ventilation to the operative lung throughout
      the procedure. The trachea was extubated in the operating room, and the patient
      recovered uneventfully from the procedure. This case demonstrates the feasibility
      of limited thoracoscopic lung resections postpneumonectomy with the use of high
      frequency jet ventilation. 

PMID- 25611748
TI  - Icetexane diterpenoids from Perovskia atriplicifolia.
AB  - Five new icetexane diterpenoids, namely, perovskatones B-D (1, 3, 4), 1alpha
      hydroxybrussonol (2), and 1alpha-hydroxypisiferanol (5), were isolated from
      Perovskia atriplicifolia, together with a new natural product (6) and two known
      compounds, przewalskin E (7) and brussonol (8). The structures of the new
      compounds were elucidated by detailed analyses of their MS, IR, 1D, and 2D NMR
      data. Compounds 1-8 were assayed for their inhibitory hepatitis B virus
      activities in the HepG 2.2.15 cell line. The results suggested that compounds 1
      and 2 possessed noticeable anti-hepatitis B virus activity in vitro, suppressing
      the replication of hepatitis B virus DNA with selectivity index values of 154.3
      and 137.7, respectively. 

PMID- 25611747
TI  - Carotid intima-media thickness at age 30, birth weight, accelerated growth during
      infancy and breastfeeding: a birth cohort study in Southern Brazil.
AB  - OBJECTIVE: To examine the relationship between carotid intima-media thickness
      (IMT) at age 30 and birth characteristics, growth during infancy, and
      breastfeeding duration, among subjects who have been prospectively followed since
      birth. METHODS AND RESULTS: In 1982, all births in the city of Pelotas, southern
      Brazil, were identified and those children (n = 5,914) whose families lived in
      the urban area of the city have been followed and evaluated at several time
      points. The cohort participants were evaluated in 2012-13, and IMT was measured
      at the posterior wall of the right and left common carotid arteries in
      longitudinal planes using ultrasound imaging. We obtained valid IMT measurements
      for 3,188 individuals. Weight-for-age z-score (WAZ) at age 2 years, weight-for
      height z-score (WHZ) at age 4, height-for-age z-score (HAZ) at 4 years, WAZ at
      age 4 and relative conditional weight at 4 years were positively associated with
      IMT, even after controlling for confounding variables. The beta-coefficient
      associated with >= 1 s.d. WAZ at age 2 (compared to those with a <-1 s.d.) was
      3.62 MUm (95% CI 0.86 to 6.38). The beta-coefficient associated with >= 1 s.d.
      WHZ at 4 (in relation to <-1 s.d) was 3.83 MUm (95% CI 0.24 to 7.42). For HAZ at
      4, the beta-coefficient for >= 1 s.d. in relation to <-1 s.d. was 4.19 MUm (95%
      CI 1.14 to 7.25). For WAZ at 4, the beta-coefficient associated with >= 1 s.d. in
      relation to <-1 s.d. was 4.28 MUm (95% CI 1.59 to 6.97). The beta-coefficient
      associated with conditional weight gain at age 2-4 was 1.26 MUm (95% CI 0.49 to
      2.02). CONCLUSION: IMT at age 30 was positively associated with WAZ at age 2
      years, WHZ at age 4, HAZ at age 4, WAZ at age 4 and conditional weight gain at
      age 4 years.

PMID- 25611749
TI  - Freestanding polyaniline nanorods grown on graphene for highly capacitive energy
      storage.
AB  - Freestanding polyaniline (PANI) nanorods grown in situ on microwave-expanded
      graphene oxide (MEGO) sheets were prepared through a facile solution method. The
      morphological characterization indicates that large quantity of free-standing
      PANI nanorods with average diameter of 50 nm were uniformly deposited onto the
      double sides of the MEGO nanosheets to form a sandwich structure. The hybrid of
      PANI/MEGO (GPANI) exhibit high specific surface area and high electrical
      conductivity, compared with pristine PANI nanorods. When evaluated as electrodes
      for supercapacitors, the GPANI demonstrate high specific capacitance of 628 F g(
      1) at a current density of 1.1 A g(-1), high-rate performance, and excellent
      cycle stability compared to individual component. Such excellent electrochemical
      performance should be attributed to the combined double-layer capacitance and
      pseudo -capacitance mechanisms from the MEGO sheets and PANI nanorods. 

PMID- 25611746
TI  - Computational analysis and low-scale constitutive expression of laccases
      synthetic genes GlLCC1 from Ganoderma lucidum and POXA 1B from Pleurotus
      ostreatus in Pichia pastoris.
AB  - Lacasses are multicopper oxidases that can catalyze aromatic and non-aromatic
      compounds concomitantly with reduction of molecular oxygen to water. Fungal
      laccases have generated a growing interest due to their biotechnological
      potential applications, such as lignocellulosic material delignification,
      biopulping and biobleaching, wastewater treatment, and transformation of toxic
      organic pollutants. In this work we selected fungal genes encoding for laccase
      enzymes GlLCC1 in Ganoderma lucidum and POXA 1B in Pleurotus ostreatus. These
      genes were optimized for codon use, GC content, and regions generating secondary
      structures. Laccase proposed computational models, and their interaction with
      ABTS [2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] substrate was
      evaluated by molecular docking. Synthetic genes were cloned under the control of
      Pichia pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) constitutive
      promoter. P. pastoris X-33 was transformed with pGAPZalphaA-LaccGluc-Stop and
      pGAPZalphaA-LaccPost-Stop constructs. Optimization reduced GC content by 47 and
      49% for LaccGluc-Stop and LaccPost-Stop genes, respectively. A codon adaptation
      index of 0.84 was obtained for both genes. 3D structure analysis using SuperPose
      revealed LaccGluc-Stop is similar to the laccase crystallographic structure 1GYC
      of Trametes versicolor. Interaction analysis of the 3D models validated through
      ABTS, demonstrated higher substrate affinity for LaccPost-Stop, in agreement with
      our experimental results with enzymatic activities of 451.08 +/- 6.46 UL-1
      compared to activities of 0.13 +/- 0.028 UL-1 for LaccGluc-Stop. This study
      demonstrated that G. lucidum GlLCC1 and P. ostreatus POXA 1B gene optimization
      resulted in constitutive gene expression under GAP promoter and alpha-factor
      leader in P. pastoris. These are important findings in light of recombinant
      enzyme expression system utility for environmentally friendly designed expression
      systems, because of the wide range of substrates that laccases can transform.
      This contributes to a great gamut of products in diverse settings: industry,
      clinical and chemical use, and environmental applications. 

PMID- 25611750
TI  - Dialysis outcomes in India: a pilot study.
AB  - AIM: Long-term prospective studies of health outcomes for dialysis patients are
      common in many parts of the world but have been rare in India. As renal
      replacement therapy becomes more widespread and more affordable, the measurement
      of patient outcomes and comparison with national and international benchmarks
      will be a valuable tool in planning health services and demonstrating effective
      use of resources. To this end, we describe a pilot study of dialysis outcomes in
      India which could form the basis of a comprehensive national programme of data
      collection. METHODS: One hundred incident patients commencing chronic
      haemodialysis in two north Indian nephrology centres will be followed
      prospectively for 12 months. Clinical outcome data will be collected comparable
      with that used by established dialysis registries in other countries. The
      economic impact of dialysis upon patients is central to the use of this
      treatment, so data will be collected on the direct and indirect costs of the
      treatment and the economic impact of dialysis on the patient and their family.
      VALUE OF PROJECT: This prospective cohort study of dialysis outcomes in northern
      India is a pilot for the collection of similar comparative data in dialysis
      centres in different states across the country with a view to the development of
      a national dialysis registry. The information on the economic impact of dialysis
      on patients and their families will provide one of the first detailed insights
      into this critical aspect of dialysis services.

PMID- 25611751
TI  - Binding strength of porphyrin-gold nanoparticle hybrids based on number and type
      of linker moieties and a simple method to calculate inner filter effects of gold
      nanoparticles using fluorescence spectroscopy.
AB  - Gold nanoparticle-porphyrin assemblies were formed by binding functionalized
      porphyrins to gold nanoparticles (Au-NPs). Spectroscopic properties of hybrids
      and binding strength of porphyrins to Au-NPs were observed based on number and
      type of linker moieties using fluorescence spectroscopy. Binding appears to be
      dependent on number rather than type of linker moieties present on the porphyrin
      molecules, as tetraaminophenyl porphyrin shows the highest binding among the
      molecules we studied and causes agglomeration of nanoparticles due to presence of
      four linker groups. The inner filter effects of Au-NPs are considerably high due
      to their high extinction coefficient and cause large errors in the evaluation of
      quenching efficiencies. We have described a very simple method to calculate the
      inner filter effects of Au-NPs by first loading them with porphyrins and then
      replacing them with nonfluorescent ligands. The difference in the fluorescence of
      unbound porphyrins in the presence and absence of Au-NPs describes their inner
      filter effects. 

PMID- 25611752
TI  - Worsening headache and nasal congestion. Lobular capillary hemangioma.

PMID- 25611754
TI  - Intraoperative transesophageal echocardiography to evaluate acute cessation of
      venous inflow during cardiopulmonary bypass.
AB  - Acute disruption of venous return during cardiopulmonary bypass (CPB) may be due
      to malposition of the venous cannula, kinks or obstruction of the venous tubing
      by a smaller cannula, airlock, or mechanical disruption of blood flow. We
      describe an acute obstruction of the venous cannula by blood clots that were
      visualized on the transesophageal echocardiogram during CPB. Appropriate measures
      were taken by the surgeon to evacuate the clot and restore CPB. The clots were
      not seen on the transesophageal echocardiogram before CPB raising suspicion that
      they originated in a lower extremity and migrated to the right atrium resulting
      in venous cannula obstruction. 

PMID- 25611753
TI  - Toward a new European threshold to discriminate illegally administered from
      naturally occurring thiouracil in livestock.
AB  - Thiouracil is a thyrostat inhibiting the thyroid function, resulting in
      fraudulent weight gain if applied in the fattening of livestock. The latter abuse
      is strictly forbidden and monitored in the European Union. Recently, endogenous
      sources of thiouracil were identified after frequently monitoring low-level
      thiouracil positive urine samples and a "recommend concentration" (RC) of 10
      MUg/L was suggested by the EURL to facilitate decision-making. However, the
      systematic occurrence of urine samples exceeding the RC led to demands for
      international surveys defining an epidemiologic threshold. Therefore, six
      European member states (France, Poland, The Netherlands, United Kingdom, Norway,
      and Belgium) have shared their official thiouracil data (2010-2012) collected
      from bovines, porcines, and small livestock with 95 and 99% percentiles of 8.1
      and 18.2 MUg/L for bovines (n = 3894); 7.4 and 13.5 MUg/L for porcines (n = 654);
      and 7.4 MUg/L (95% only) for small livestock (n = 85), respectively. Bovine
      percentiles decreased with the animal age (nonadults had significantly higher
      levels for bovines), and higher levels were observed in male bovines compared to
      female bovines.

PMID- 25611755
TI  - Editorial comment: intraoperative transesophageal echocardiography to evaluate
      acute cessation of venous inflow during cardiopulmonary bypass.

PMID- 25611756
TI  - Facilitating transesophageal echocardiography probe placement by esophageal
      bougie in an anesthetized patient.
AB  - The reported adverse effects of perioperative transesophageal echocardiography
      (TEE) are mostly associated with the insertion and manipulation of the TEE probe.
      Recent data suggest that blind probe insertion may be associated with greater
      morbidity than reported previously. Although this morbidity appears to be
      subclinical with unknown effects on patient outcome, evaluation of strategies for
      insertion is warranted. Herein, we present a novel insertion technique using a
      soft-tipped esophageal bougie as a guide for blind TEE probe insertion in a
      patient undergoing cardiac surgery. The potential advantages and related safety
      issues are discussed. 

PMID- 25611757
TI  - Management of labor analgesia in a patient with acute myeloid leukemia.
AB  - The anesthetic implications of acute leukemia in pregnancy have not been
      reported. We describe the anesthetic management of a laboring primigravida at 34
      weeks' gestation with new-onset acute myeloid leukemia. With multidisciplinary
      consultation, we recommend that neuraxial anesthesia be avoided in new-onset
      acute myeloid leukemia due to the risk of introducing malignant cells into the
      central nervous system, which can spread the disease and complicate management.
      We discuss the use of a fentanyl patient-controlled analgesia and dexmedetomidine
      as a method of labor analgesia, and the potential benefits of the latter
      medication in the obstetric population. 

PMID- 25611758
TI  - Intraoperative diagnosis and treatment of thyroid storm in a 15-year-old male.
AB  - Thyroid storm, a severe complication of hyperthyroidism, can be a devastating
      medical emergency requiring rapid management. Intraoperative thyrotoxicosis, a
      hypermetabolic syndrome with increased thyroid hormone levels, also presents a
      challenging scenario. Clinical suspicion is key along with eliminating other
      potentially catastrophic emergencies such as malignant hyperthermia or
      pheochromocytoma. In this case report, we describe a 15-year-old male undergoing
      halo traction placement for displaced dens and C1 fractures. Preoperative
      tachycardia and a history suggestive of hyperthyroidism raised our clinical
      suspicion for thyrotoxicosis when hypertension and tachycardia developed after
      induction of anesthesia. 

PMID- 25611759
TI  - Failure to Isolate the Right Lung with an EZ-Blocker.

PMID- 25611760
TI  - Epinephrine to Reduce Local Anesthetic Systemic Toxicity in Patients Receiving
      TAP Blocks.

PMID- 25611761
TI  - In response.

PMID- 25611763
TI  - Nitrenium ion analogues of nonclassical carbocations: cyclopropylnitrenium,
      allylnitrenium, and azetidenium ions and mechanisms for their interconversion.
AB  - Cyclopropylnitrenium 3S, allylnitreium 6S, and azetidenium (i.e., the nitrogen
      analogue of cyclobutylcarbenium) ions were examined using density functional
      theory and a complete basis set method. Similarly to the carbon analogues, the
      singlet states of these species have several local minima with nonclassical
      bonding. Structures characterized include 3S, an N analogue of the bisected
      cyclopropylcarbinyl cation, 11S, an N analogue of the bicyclobutonium ion, and
      6S, an unsymmetric 2-azidinylcarbinyl cation. 

PMID- 25611764
TI  - Controlling structure and porosity in catalytic nanoparticle superlattices with
      DNA.
AB  - Herein, we describe a strategy for converting catalytically inactive, highly
      crystalline nanoparticle superlattices embedded in silica into catalytically
      active, porous structures through superlattice assembly and calcination. First, a
      body-centered cubic (bcc) superlattice is synthesized through the assembly of two
      sets of 5 nm gold nanoparticles chemically modified with DNA bearing
      complementary sticky end sequences. These superlattices are embedded in silica
      and calcined at 350  degrees C to provide access to the catalytic nanoparticle
      surface sites. The calcined superlattice maintains its bcc ordering and has a
      surface area of 210 m(2)/g. The loading of catalytically active nanoparticles
      within the superlattice was determined by inductively coupled plasma mass
      spectrometry, which revealed that the calcined superlattice contained
      approximately 10% Au by weight. We subsequently investigate the ability of
      supported Au nanoparticle superlattices to catalyze alcohol oxidation. In
      addition to demonstrating that calcined superlattices are effective catalysts for
      alcohol oxidation, electron microscopy reveals preservation of the crystalline
      structure of the bcc superlattice following calcination and catalysis. Unlike
      many bulk nanoparticle catalysts, which are difficult to characterize and
      susceptible to aggregation, nanoparticle superlattices synthesized using DNA
      interactions offer an attractive bottom-up route to structurally defined
      heterogeneous catalysts, where one has the potential to independently control
      nanoparticle size, nanoparticle compositions, and interparticle spacings. 

PMID- 25611765
TI  - The age-specific prevalence of myopia in Asia: a meta-analysis.
AB  - PURPOSE: To estimate the age-specific prevalence of myopia in Asia. METHODS: We
      searched PubMed, Embase, and Web of Science from their inception through
      September 2013 for population-based surveys reporting the prevalence of myopia in
      adults or children in Asia. We pooled the prevalence estimates for myopia by age
      groups and by year of birth using a random-effects model. RESULTS: We identified
      50 eligible population-based studies including 215,672 subjects aged 0 to 96
      years reporting the prevalence of myopia from 16 Asian countries or regions.
      Myopia was found to be most prevalent (96.5%; 95% confidence interval, 96.3 to
      96.8) in Koreans aged 19 years. There was no significant linear age group effect
      on the prevalence of myopia in the whole Asian population but there was a U
      shaped relationship between both age and year of birth and the prevalence of
      myopia. The prevalence of myopia was also higher in those older than 70 years
      (36.3%; 95% confidence interval, 27.6 to 45.0) compared with other age groups,
      which revealed nuclear cataract-myopia shifts in refraction. CONCLUSIONS: There
      is a large variation in the age-specific prevalence of myopia in Asia. A U-shaped
      relationship between age and the prevalence of myopia was found in the whole
      Asian population. The analysis is essential to guide future eye health care,
      intervention, and clinical management in Asia.

PMID- 25611762
TI  - Predicting and influencing voice therapy adherence using social-cognitive factors
      and mobile video.
AB  - PURPOSE: Patient adherence to voice therapy is an established challenge. The
      purpose of this study was (a) to examine whether adherence to treatment could be
      predicted from three social-cognitive factors measured at treatment onset: self
      efficacy, goal commitment, and the therapeutic alliance, and (b) to test whether
      the provision of clinician, self-, and peer model mobile treatment videos on MP4
      players would influence the same triad of social cognitive factors and the
      adherence behavior of patients. METHOD: Forty adults with adducted hyperfunction
      with and without benign lesions were prospectively randomized to either 4
      sessions of voice therapy enhanced by MP4 support or without MP4 support.
      Adherence between sessions was assessed through self-report. Social cognitive
      factors and voice outcomes were assessed at the beginning and end of therapy.
      Utility of MP4 support was assessed via interviews. RESULTS: Self-efficacy and
      the therapeutic alliance predicted a significant amount of adherence variance.
      MP4 support significantly increased generalization, self-efficacy for
      generalization, and the therapeutic alliance. An interaction effect demonstrated
      that MP4 support was particularly effective for patients who started therapy with
      poor self-efficacy for generalization. CONCLUSION: Adherence may be predicted and
      influenced via social-cognitive means. Mobile technology can extend therapy to
      extraclinical settings.

PMID- 25611766
TI  - Fulminant intraoperative right heart and pulmonary artery thrombosis following
      prothrombin complex concentrate infusion after complex open heart surgery with
      cardiopulmonary bypass.
AB  - Prothrombin complex concentrates are increasingly used during complex cardiac
      surgery with cardiopulmonary bypass. Reports describing massive thromboembolism
      after administration of prothrombin complex concentrates are rare. We report a
      case of a patient developing massive intracardiac and pulmonary artery thrombus
      formations during infusion of a moderate dose of prothrombin complex concentrate
      after separation from cardiopulmonary bypass for complex open heart surgery. 

PMID- 25611767
TI  - Coronary artery bypass grafting in 2 thrombophilic patients with protein s
      deficiency.
AB  - In this report, we review 2 cases of coronary revascularization in patients with
      a diagnosis of coronary artery disease and preoperative protein S deficiency, an
      established hypercoagulable condition. In an attempt to normalize protein S
      levels, fresh frozen plasma was used as the priming fluid for the cardiopulmonary
      bypass circuit before the initiation of extracorporeal circulation. On the basis
      of a low risk of bleeding and the theoretical risk of thrombosis, neither patient
      received intraoperative antifibrinolytic treatment nor did they develop
      perioperative thrombotic complications. 

PMID- 25611768
TI  - Editorial comment: "coronary artery bypass grafting in 2 thrombophilic patients
      with protein s deficiency" and "fulminant intraoperative right heart and
      pulmonary artery thrombosis following prothrombin complex concentrate infusion
      after complex open heart surgery with cardiopulmonary bypass".

PMID- 25611769
TI  - Airway obstruction mimicking superior vena cava syndrome in a patient undergoing
      dialysis graft revision after ultrasound-guided supraclavicular nerve block.
AB  - A 25-year-old man presented for revision of a dialysis fistula in his left upper
      arm. An ultrasound-guided left supraclavicular block was performed, and 4 hours
      later during wound closure, the patient developed intermittent airway obstruction
      accompanied by edema of the face and upper airway. Superior vena cava syndrome
      was suspected, and awake fiberoptic tracheal intubation was performed. Partial
      obstruction of the left brachiocephalic vein and right internal jugular vein were
      identified while the patient was in the radiology suite. Sympathetic block and
      increased venous return from the left arm likely contributed to his airway
      obstruction that mimicked superior vena cava syndrome. 

PMID- 25611770
TI  - Anesthetic implications of extended right hepatectomy in a patient with fontan
      physiology.
AB  - Patients who have undergone complete cavopulmonary anastomosis, the Fontan
      procedure, have passive venous blood flow from the superior and inferior vena
      cava into the pulmonary circulation without passing through the right ventricle.
      Although this procedure is an effective means of palliation, the resultant
      chronically increased central venous pressure, leads to several types of hepatic
      dysfunction including chronic congestion, cardiac cirrhosis, and even
      hepatocellular carcinoma. In this case report, we describe a patient with Fontan
      associated hepatocellular carcinoma who successfully underwent a right
      hepatectomy. 

PMID- 25611771
TI  - From the guest editor: The sentinel node: evolution of the revolution.
      Introduction.

PMID- 25611772
TI  - The history of sentinel lymph node biopsy.
AB  - The sentinel node biopsy technique, developed by Drs Donald Morton and Alistair
      Cochran and reported in 1992, undoubtedly constitutes the most important recent
      development in surgical oncology. This article describes the evolution of the
      procedure and its contribution to the evolution of modern multidisciplinary
      cancer care and discusses its present role in the management of patients with
      melanoma, breast cancer, and a wide range of other malignancies. 

PMID- 25611774
TI  - Sentinel lymph node biopsy and nodal ultrastaging in colorectal cancer.
AB  - The tumor status of the regional lymph nodes is the most important prognostic
      indicator in colorectal cancer (CRC), as it is in other solid tumors. Sentinel
      lymph node biopsy (SLNB), which has profoundly impacted the treatment of melanoma
      and breast cancer, has been applied in CRC in an attempt to improve nodal staging
      accuracy. The challenge lies in identifying patients who have tumor-negative
      nodes but are at high risk of regional or distant failure and therefore may
      benefit from adjuvant chemotherapy. Because standard pathological analysis of
      lymph nodes may incorrectly stage colon cancer, multiple studies have
      investigated nodal ultrastaging based on identification and immunohistochemical
      and/or molecular assessment of the sentinel node. This review focuses on the
      technique of SNLB, its feasibility and validity, and the controversies that
      remain regarding the clinical significance of nodal ultrastaging in CRC. 

PMID- 25611773
TI  - Sentinel lymph node biopsy in breast cancer: a work in progress.
AB  - The sentinel lymph node biopsy is a safe, accurate operation for the initial
      staging of breast cancer. Over the last decade, there has been increasing
      literature supporting its use, and it is now considered a standard of care for
      the initial evaluation of metastatic spread to the axillary lymph node chain. 

PMID- 25611775
TI  - Status of sentinel lymph node mapping in non-small cell lung cancer.
AB  - Sentinel lymph node mapping has become the standard of care in melanoma and
      breast cancer, contributing to marked improvements in accurate staging and
      targeted treatment, while decreasing morbidity of aggressive nodal bed
      dissections. Since 1999, several groups have proposed similar mapping in lung
      cancer models with mixed success. This article reviews the research up to date
      and discusses opportunities to improve accuracy of sentinel lymph node biopsy in
      non-small cell lung cancer. 

PMID- 25611776
TI  - Sentinel lymph node biopsy in gastric cancer.
AB  - Clinical application of sentinel lymph node (SLN) mapping in patients with early
      stage gastric cancer has been a controversial issue for years. However, a recent
      meta-analysis and a prospective multicenter trial of SLN mapping for early-stage
      gastric cancer have shown acceptable SLN detection rates and accuracy of
      determination of lymph node status. A dual-tracer method that uses radioactive
      colloids and blue dyes is currently considered the most reliable method for the
      stable detection of SLNs in patients with early-stage gastric cancer. However,
      the new technologies such as indocyanine green infrared or fluorescence imaging
      might revolutionize the SLN mapping procedures in gastric cancer. For early-stage
      gastric cancer, the establishment of individualized, minimally invasive
      treatments based on SLN concept may retain the patients' quality of life. 

PMID- 25611777
TI  - Imaging sentinel lymph nodes.
AB  - As the technique of sentinel lymph node (SLN) biopsy has evolved over the last 22
      years, it has become increasingly evident that accurate SLN imaging is vital to
      allow surgical removal of only the true SLN(s) and not other nodes. Identifying
      the lymphatic collectors draining a tumor site and following them to the draining
      SLNs defines which nodes need to be removed for careful histologic examination.
      Current technology allows the exact location of each SLN to be defined. This
      allows the full benefits of SLN biopsy to be achieved, that is, highly accurate
      lymph node staging with minimal morbidity. In melanoma and breast cancer, the
      current practice of preoperative lymphoscintigraphy (LS) using peritumoral
      injections of tracer or injection adjacent to an excision biopsy site with
      dynamic imaging to visualize the lymphatic collectors and delayed imaging
      including single-photon emission computed tomography/computed tomography gives
      the best results. This information informs the surgical approach and allows rapid
      excision of the SLNs at surgery.In patients with visceral tumors where the
      primary cancer site is difficult to access, it appears that using fluorophores
      that are fluorescent under near-infrared light, injected during surgery, is
      evolving as the preferred technique.

PMID- 25611778
TI  - Pathologic evaluation of sentinel nodes.
AB  - Optimal utilization of sentinel node biopsy in the care of cancer patients
      requires cooperation between the radiologist, surgeon, and the pathologist.
      Accurate pathologic diagnosis of the sentinel node is central to correct staging,
      optimal treatment decisions, and precise prognostication of patients with
      melanoma, breast, colorectal, lung, and gastric cancer. Intraoperative handling,
      gross dissection, and histologic/immunohistochemical evaluation techniques are
      all key components of this process. Although not currently part of routine
      handling, newer molecular techniques may potentially add to the valuable
      information gained from evaluating sentinel node specimens. 

PMID- 25611779
TI  - Is sentinel node susceptibility to metastases related to nodal immune modulation?
AB  - Sentinel lymph nodes (SLNs), the initial site of regional metastases, directly
      receive lymph containing immune-modulatory cytokines and tumor cells from primary
      melanomas. Immune-suppressed SLNs are ideal for studies of tissue susceptibility
      to metastases. They show reduced antigen-presenting dendritic cells, activated T
      cells, high endothelial venules, and transvenular immigration of T cells. Tumor
      induced immune suppression contributes to establishment of nodal metastases. SLNs
      may serve as an effective model to study reversal of tumor-induced immune
      suppression. We reviewed this topic in Nature Reviews of Immunology in 2006. We
      here summarize the Nature paper and provide additional results from ongoing
      studies and the recent literature. 

PMID- 25611780
TI  - Thioboration of alpha,beta-unsaturated ketones and aldehydes toward the synthesis
      of beta-sulfido carbonyl compounds.
AB  - Herein a direct beta-sulfido carbonyl compound synthesis by the easy activation
      of RS-Bpin reagents with alpha,beta-unsaturated ketones and aldehydes is
      reported. This convenient methodology can be performed at room temperature with
      no other additives. The key point of this reactivity is based on the Lewis acidic
      properties of the boryl unit of the RS-Bpin reagent interacting with the C?O
      oxygen. Consequently, the SR unit becomes more nucleophilic and promotes the 1,4-
      versus the 1,2-addition, as a function of the involved substrate. The thioborated
      products can be further transformed into beta-sulfido carbonyl compounds by
      addition of MeOH. 

PMID- 25611781
TI  - The challenge presented by progestins in ecotoxicological research: a critical
      review.
AB  - Around 20 progestins (also called gestagens, progestogens, or progestagens) are
      used today in assisting a range of medical conditions from endometrial cancer to
      uterine bleeding and as an important component of oral contraception. These
      progestins can bind to a wide range of receptors including progestin, estrogen,
      androgen, glucocorticoid, and mineralocorticoid receptor, as well as sex hormone
      and corticosteroid binding globulins. It appears that only five of these (four
      synthetic and one natural) progestins have so far been studied in sewage effluent
      and surface waters. Analysis has reported values as either nondetects or low
      nanograms per liter in rivers. Seven of the progestins have been examined for
      their effects on aquatic vertebrates (fish and frogs). The greatest concern is
      associated with levonorgestrel, norethisterone, and gestodene and their ability
      to reduce egg production in fish at levels of 0.8-1.0 ng/L. The lack of
      environmental measurements, and some of the contradictions in existing values,
      however, hampers our ability to make a risk assessment. Only a few nanograms per
      liter of ethynodiol diacetate and desogestrel in water would be needed for fish
      to receive a human therapeutic dose for these progestins according to modeled
      bioconcentration factors. But for the other synthetic progestins levels would
      need to reach tens or hundreds of nanograms per liter to achieve a therapeutic
      dose. Nevertheless, the wide range of compounds, diverse receptor targets, and
      the effect on fish reproduction at sub-nanogram-per-liter levels should prompt
      further research. The ability to impair female reproduction at very low
      concentrations makes the progestins arguably the most important pharmaceutical
      group of concern after ethinylestradiol. 

PMID- 25611782
TI  - Single-molecule resolution of protein dynamics on polymeric membrane surfaces:
      the roles of spatial and population heterogeneity.
AB  - Although polymeric membranes are widely used in the purification of protein
      pharmaceuticals, interactions between biomolecules and membrane surfaces can lead
      to reduced membrane performance and damage to the product. In this study, single
      molecule fluorescence microscopy provided direct observation of bovine serum
      albumin (BSA) and human monoclonal antibody (IgG) dynamics at the interface
      between aqueous buffer and polymeric membrane materials including regenerated
      cellulose and unmodified poly(ether sulfone) (PES) blended with either
      polyvinylpyrrolidone (PVP), polyvinyl acetate-co-polyvinylpyrrolidone (PVAc-PVP),
      or polyethylene glycol methacrylate (PEGM) before casting. These polymer surfaces
      were compared with model surfaces composed of hydrophilic bare fused silica and
      hydrophobic trimethylsilane-coated fused silica. At extremely dilute protein
      concentrations (10(-3)-10(-7) mg/mL), protein surface exchange was highly dynamic
      with protein monomers desorbing from the surface within ~1 s after adsorption.
      Protein oligomers (e.g., nonspecific dimers, trimers, or larger aggregates),
      although less common, remained on the surface for 5 times longer than monomers.
      Using newly developed super-resolution methods, we could localize adsorption
      sites with ~50 nm resolution and quantify the spatial heterogeneity of the
      various surfaces. On a small anomalous subset of the adsorption sites, proteins
      adsorbed preferentially and tended to reside for significantly longer times
      (i.e., on "strong" sites). Proteins resided for shorter times overall on surfaces
      that were more homogeneous and exhibited fewer strong sites (e.g., PVAc-PVP/PES).
      We propose that strong surface sites may nucleate protein aggregation, initiated
      preferentially by protein oligomers, and accelerate ultrafiltration membrane
      fouling. At high protein concentrations (0.3-1.0 mg/mL), fewer strong adsorption
      sites were observed, and surface residence times were reduced. This suggests that
      at high concentrations, adsorbed proteins block strong sites from further protein
      adsorption. Importantly, this demonstrates that strong binding sites can be
      modified by changing solution conditions. Membrane surfaces are intrinsically
      heterogeneous; by employing single-molecule techniques, we have provided a new
      framework for understanding protein interactions with such surfaces. 

PMID- 25611783
TI  - Influence of antifreeze proteins on the ice/water interface.
AB  - Antifreeze proteins (AFP) are responsible for the survival of several species,
      ranging from bacteria to fish, that encounter subzero temperatures in their
      living environment. AFPs have been divided into two main families, moderately and
      hyperactive, depending on their thermal hysteresis activity. We have studied one
      protein from both families, the AFP from the snow flea (sfAFP) and from the
      winter flounder (wfAFP), which belong to the hyperactive and moderately active
      family, respectively. On the basis of molecular dynamics simulations, we have
      estimated the thickness of the water/ice interface for systems both with and
      without the AFPs attached onto the ice surface. The calculation of the diffusion
      profiles along the simulation box allowed us to measure the interface width for
      different ice planes. The obtained widths clearly show a different influence of
      the two AFPs on the ice/water interface. The different impact of the AFPs here
      studied on the interface thickness can be related to two AFPs properties: the
      protein hydrophobic surface and the number of hydrogen bonds that the two AFPs
      faces form with water molecules. 

PMID- 25611784
TI  - Recent advances in myelodysplastic syndromes: Molecular pathogenesis and its
      implications for targeted therapies.
AB  - Myelodysplastic syndromes (MDS) are defined as stem cell disorders caused by
      various gene abnormalities. Recent analysis using next-generation sequencing has
      provided great advances in identifying relationships between gene mutations and
      clinical phenotypes of MDS. Gene mutations affecting RNA splicing machinery, DNA
      methylation, histone modifications, transcription factors, signal transduction
      proteins and components of the cohesion complex participate in the pathogenesis
      and progression of MDS. Mutations in RNA splicing and DNA methylation occur early
      and are considered "founding mutations", whereas others that occur later are
      regarded as "subclonal mutations". RUNX1 mutations are more likely to subclonal;
      however, they apparently play a pivotal role in familial MDS. These genetic
      findings may lead to future therapies for MDS. 

PMID- 25611785
TI  - Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2
      inflammation in chronic obstructive pulmonary disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a heterogeneous
      disease and likely includes a subgroup that is biologically comparable to asthma.
      Studying asthma-associated gene expression changes in COPD could add insight into
      COPD pathogenesis and reveal biomarkers that predict a favorable response to
      corticosteroids. OBJECTIVES: To determine whether asthma-associated gene
      signatures are increased in COPD and associated with asthma-related features.
      METHODS: We compared disease-associated airway epithelial gene expression
      alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171).
      The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced
      in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was
      correlated with asthma-related features and response to corticosteroids in COPD
      in a randomized, placebo-controlled trial, the Groningen and Leiden Universities
      study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89).
      MEASUREMENTS AND MAIN RESULTS: The 200 genes most differentially expressed in
      asthma versus healthy control subjects were enriched among genes associated with
      more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting
      significant gene expression overlap. A higher T2S score was associated with
      decreased lung function (P < 0.001), but not asthma history, in both COPD
      cohorts. Higher T2S scores correlated with increased airway wall eosinophil
      counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator
      reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid
      treatment (P = 0.019) in GLUCOLD. CONCLUSIONS: These data identify airway gene
      expression alterations that can co-occur in asthma and COPD. The association of
      the T2S score with increased severity and "asthma-like" features (including a
      favorable corticosteroid response) in COPD suggests that Th2 inflammation is
      important in a COPD subset that cannot be identified by clinical history of
      asthma.

PMID- 25611787
TI  - Np(v) complexation with propionate in 0.5-4 M NaCl solutions at 20-85  degrees C.
AB  - Low molecular weight organics (LMWO; e.g. acetate, propionate, lactate) can
      significantly impact the speciation and mobility of radionuclides in aqueous
      media. Natural clay rock formation, considered as a potential host rock for
      nuclear waste disposal, can contain a significant amount of organic matter. There
      are less thermodynamic data reported for the complexation of pentavalent
      actinides with LMWO, especially under elevated temperature conditions, relevant
      for assessing the long-term safety of disposal options for heat-producing high
      level nuclear waste. In the present study, the complexation of Np(v) with
      propionate is studied using spectroscopic techniques in 0.5-4 M NaCl solutions by
      systematic variation of the ligand concentration and temperature. Slope analysis
      shows the formation of the 1 : 1 NpO2-propionate complex (NpO2Prop). The local
      structure of the NpO2-propionate complex is determined by extended X-ray
      absorption fine structure spectroscopy, the results of which suggest that
      propionate binds to Np(v) in a bidentate mode. Using the specific ion interaction
      theory (SIT), the stability constant at zero ionic strength and 25  degrees C is
      determined as log beta degrees 1,1 = 1.26 +/- 0.03. The stability constants
      increase continuously with increasing temperature between 20 and 85  degrees C.
      The log beta0 values are linearly correlated with the reciprocal temperature,
      indicating DeltarH = const. and DeltarC = 0, allowing the calculation of DeltarH
      and DeltarS for the formation of the NpO2-propionate complex using the integrated
      van't Hoff equation. The thermodynamic evaluation indicates that the reaction is
      endothermic and entropy driven. 

PMID- 25611786
TI  - Quantifying renal allograft loss following early antibody-mediated rejection.
AB  - Unlike antibody-mediated rejection (AMR) with clinical features, it remains
      unclear whether subclinical AMR should be treated, as its effect on allograft
      loss is unknown. It is also uncertain if AMR's effect is homogeneous across donor
      (deceased/live) and (HLA/ABO) antibody types. We compared 219 patients with AMR
      (77 subclinical, 142 clinical) to controls matched on HLA/ABO-compatibility,
      donor type, prior transplant, panel reactive antibody (PRA), age and year. One
      and 5-year graft survival in subclinical AMR was 95.9% and 75.7%, compared to
      96.8% and 88.4% in matched controls (p = 0.0097). Subclinical AMR was
      independently associated with a 2.15-fold increased risk of graft loss (95% CI:
      1.19-3.91; p = 0.012) compared to matched controls, but not different from
      clinical AMR (p = 0.13). Fifty three point two percent of subclinical AMR
      patients were treated with plasmapheresis within 3 days of their AMR-defining
      biopsy. Treated subclinical AMR patients had no difference in graft loss compared
      to matched controls (HR 1.73; 95% CI: 0.73-4.05; p = 0.21), but untreated
      subclinical AMR patients did (HR 3.34; 95% CI: 1.37-8.11; p = 0.008). AMR's
      effect on graft loss was heterogeneous when stratified by compatible deceased
      donor (HR = 4.73; 95% CI: 1.57-14.26; p = 0.006), HLA-incompatible deceased donor
      (HR = 2.39; 95% CI: 1.10-5.19; p = 0.028), compatible live donor (no AMR patients
      experienced graft loss), ABO-incompatible live donor (HR = 6.13; 95% CI: 0.55
      67.70; p = 0.14) and HLA-incompatible live donor (HR = 6.29; 95% CI: 3.81-10.39;
      p < 0.001) transplant. Subclinical AMR substantially increases graft loss, and
      treatment seems warranted.

PMID- 25611788
TI  - Improved Raman and photoluminescence sensitivity achieved using bifunctional
      Ag@SiO2 nanocubes.
AB  - SiO2 coated silver nanocubes Ag@SiO2 with enhanced surface-enhanced Raman
      scattering (SERS) and metal enhanced photoluminescence (MEPL) sensitivity were
      synthesized and characterized. The silver nanocubes (NCs) were synthesized by the
      polyol method and modified, first with different coupling agents, such as 3
      mercaptopropyltrimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APS),
      and secondly with tetraethylorthosilicate (TEOS) to improve their SERS and
      photoluminescence (PL) performances. The SERS and PL intensity of rhodamine 6G
      (R6G) can be manipulated by tuning the Ag nanocube's SiO2 shell thickness.
      Modified Ag NCs (with a 2 nm silica layer) were prepared using 1 mM APS and 1 mM
      TEOS and found to have a SERS intensity 3 fold higher than bare Ag NCs.
      Additionally, it was found that APS modified Ag@SiO2 NCs possessed both enhanced
      SERS and PL intensities. 

PMID- 25611789
TI  - Periodization and physical performance in elite female soccer players.
AB  - PURPOSE: To investigate the variation in training demands, physical performance,
      and player well-being across a women's soccer season. METHODS: Seventeen elite
      female players wore GPS tracking devices during every training session (N=90)
      throughout 1 national-league season. Intermittent high-speed-running capacity and
      5-, 15-, and 25-m-sprint testing were conducted at the beginning of preseason,
      end of preseason, midseason, and end of season. In addition, subjective well
      being measures were self-reported daily by players over the course of the season.
      RESULTS: Time over 5 m was lowest at the end of preseason (mean 1.148 s, SE 0.017
      s) but then progressively deteriorated to the end of the season (P<.001). Sprint
      performance over 15 m improved by 2.8% (P=.013) after preseason training, while
      25-m-sprint performance peaked at midseason, with a 3.1% (P=.05) improvement from
      the start of preseason, before declining at the end of season (P=.023). Training
      demands varied between phases, with total distance and high-speed distance
      greatest during preseason before decreasing (P<.001) during the early- and late
      season phases. Endurance capacity and well-being measures did not change across
      training phases. CONCLUSIONS: Monitoring training demands and subsequent physical
      performance in elite female soccer players allow coaches to ensure that training
      periodization goals are being met and related positive training adaptations are
      being elicited.

PMID- 25611790
TI  - The tempo of trait divergence in geographic isolation: avian speciation across
      the Maranon Valley of Peru.
AB  - Geographic isolation is considered essential to most speciation events, but our
      understanding of what controls the pace and degree of phenotypic divergence among
      allopatric populations remains poor. Why do some taxa exhibit phenotypic
      differentiation across barriers to dispersal, whereas others do not? To test
      factors controlling phenotypic divergence in allopatry, we employed a comparative
      phylogeographic approach consisting of replicates of ecologically similar Andean
      bird species isolated across a major biogeographic barrier, the Maranon Valley of
      Peru. Our study design leverages variation among codistributed taxa in their
      degree of plumage, morphometric, and vocal differentiation across the Maranon to
      examine the tempo of phenotypic evolution. We found that substantial plumage
      differences between populations required roughly two million years to evolve. In
      contrast, morphometric trait evolution showed greater idiosyncrasy and stasis.
      Our results demonstrate that despite a large degree of idiosyncrasy in the
      relationship between genetic and phenotypic divergence across taxa and
      environments, comparative studies within regions may reveal predictability in the
      pace of phenotypic divergence. Our results also suggest that social selection is
      important for driving differentiation of populations found in similar
      environments. 

PMID- 25611791
TI  - The concordance of ultrasound technique versus X-ray to confirm endotracheal tube
      position in neonates.
AB  - OBJECTIVE: Given the distressingly high incidence of ETT malposition in the
      neonatal population, patients are exposed to ionizing radiation to confirm
      endotracheal tube (ETT) position. Our objective is to determine if ultrasound
      technique is concordant with X-ray in determining whether an ETT is deeply
      positioned or not. STUDY DESIGN: Prospective observational clinical trial. After
      obtaining informed consent, patients with an ETT who required X-ray for clinical
      reasons underwent sonographic evaluation of the ETT by an ultrasound technologist
      or pediatric radiologist, usually within the hour. RESULTS: A total of 56 image
      pairs were obtained from 29 patients. Ninety-eight percent of the ultrasound/X
      ray image pairs were suitable for analysis. The concordance of ultrasound with X
      ray to identify deeply and not deeply positioned ETTs was 95% (53/56). The
      sensitivity of ultrasound to detect deeply positioned ETTs on X-ray was 86%
      (6/7). The specificity of ultrasound to detect ETTs that were not deeply
      positioned on X-ray was 96% (47/49). CONCLUSIONS: As the largest clinical trial
      of its kind to date, with the greatest number of ultrasound operators, we have
      further established US as a feasible imaging modality to determine whether an ETT
      is deeply positioned or not.

PMID- 25611792
TI  - Dutch pediatricians' views on the use of neuromuscular blockers for dying
      neonates: a qualitative study.
AB  - OBJECTIVE: To assess Dutch pediatricians' views on neuromuscular blockers for
      dying neonates. STUDY DESIGN: Qualitative study involving in-depth interviews
      with 10 Dutch pediatricians working with severely ill neonates. Data were
      analyzed using appropriate qualitative research techniques. RESULT: Participants
      explained their view on neuromuscular blockers for neonates with a protracted
      dying process. Major themes were the interpretation of gasping, the role of (the
      suffering of) the parents, the need for judicial review and legislation's impact
      on the care participants provide for dying neonates. CONCLUSION: The interviews
      show no consensus between pediatricians and provide insights into the points of
      disagreement. Interviews also suggest friction between the convictions of
      pediatricians and legislation, which seems to have an undesirable impact on Dutch
      care for dying neonates and their parents. This study raises important questions
      for pediatricians worldwide to reflect upon, such as: 'what constitutes 'dying
      well'?' and 'what role should the parents' perspective play?'.

PMID- 25611793
TI  - Simple measurements to place umbilical catheters using surface anatomy.
AB  - OBJECTIVE: To use external anatomical landmarks to determine a new method for the
      estimation of appropriate insertion length of umbilical catheters, suitable for
      newborn infants of varying birth weight (BW) and gestational age. STUDY DESIGN:
      Neonates who had umbilical venous (UVC) or arterial (UAC) catheters placed soon
      after birth were included in the study. Catheters were placed using formulas
      derived by Shukla (1986) and/or Wright (2007), and adjusted to appropriate
      positions confirmed radiologically: UAC tip between T6-T10 vertebral bodies and
      UVC at the level of the diaphragm+/-0.5 cms. Final catheter length was compared
      with the length estimated by Shukla/Wright formulas and to four additional
      morphometric measurements: umbilicus to nipple (UN), umbilicus to midpoint of
      inter-mammary distance, umbilicus to xiphoid process and umbilicus to symphysis
      pubis (USp). RESULT: Of 216 infants, 32 were excluded; UVC was placed in 170
      infants and UAC in 125 infants. Among the morphometric measurements, UN-1 cm ( UN
      distance minus 1 cm) provided the best estimate of accurate insertion length of
      UVC, (r=0.984, P<0.001) and estimated correct insertion length of 94% of UVCs
      compared with 57% accuracy with Shukla formula for all BW categories (P<0.001).
      Morphometric measurement UN-1+2 USp (UN distance minus 1 cm plus twice the
      distance from umbilicus to symphysis pubis) showed significantly better
      correlation with appropriate insertion length of UAC (r=0.985, P<0.001) and
      estimated correct insertion length of 92% of UACs in all infants as compared with
      57% accuracy with Shukla formula (P<0.001), and the correct insertion length in
      94% of very low BW infants as compared with 68% accuracy with Wright formula
      (P<0.001). CONCLUSION: Simple and intuitive morphometric measurements UN and USp
      provide more accurate estimates of appropriate insertion lengths for umbilical
      catheters in infants with all BWs than commonly used BW-based formulas.

PMID- 25611794
TI  - Nanometal surface energy transfer optical ruler for measuring a human telomere
      structure.
AB  - Nanometal surface energy transfer (NSET) techniques on gold nanoparticles (AuNPs)
      have become an essential tool in molecular biophysics to identify structural
      details at long-range donor-acceptor distances. The NSET mechanism is well
      described, but it has been suggested that the use of large AuNPs in NSET may
      manipulate natural biomolecular function. If, in fact, such nonspecific
      interactions with the AuNP surface can be quantified or contained, then NSET may
      offer more potential in tracking biomolecular folding than the most comprehensive
      methods in conformer determination (X-ray crystallography, NMR, EPR). Here, we
      describe an NSET ruler capable of tracking Hybrid-2 telomere quadruplex folding
      and we demonstrate that nucleic acid appendage to AuNPs up to 10 nm in diameter
      does not manipulate biomolecular function. The quadruplex folding of Hybrid-2
      sequences was tracked by monitoring the emission of a DY680 dye on selected
      basepairs in the telomere sequence when appended to the surface of AuNPs (5-10
      nm). Emission-derived distances extracted from NSET theory correlate well to
      reported NMR structures of the hybrid quadruplex. Moreover, NSET theory
      calculates identical donor-acceptor distal points between DY680 and all sizes of
      AuNPs, indicating that the AuNP tether is not dominant or disruptive towards
      nucleic acid folding.

PMID- 25611795
TI  - The oxidative stress, antioxidant profile and acid-base status in preterm and
      term canine neonates.
AB  - During the initiation of neonatal pulmonary respiration, there is an exponential
      increase in reactive oxygen species that must be scavenged by antioxidant
      defences. However, neonate and preterm newborns are known to possess immature
      antioxidant mechanisms to neutralize these toxic effects. The purposes of this
      study were to compare the development of antioxidant system between preterm and
      term canine neonates and to evaluate the magnitude of acid-base balance during
      the initial 4 h of life. A prospective study was conducted involving 18 neonatal
      puppies assigned to Term Group (63 days of gestation; n = 5), Preterm-57 Group
      (57 days of gestation; n = 8) and Preterm-55 Group (55 days of gestation; n = 5).
      Neonates were physically examined through Apgar score and venous haemogasometry
      within 5 min, 2 and 4 h after birth. No difference on amniotic fluid and serum
      superoxide dismutase (SOD), glutathione peroxidase (GPx) and the marker of
      oxidative stress (thiobarbituric acid reactive substances; TBARS) was verified.
      Irrespective of prematurity, all neonates presented low vitality, hypothermia,
      acidosis, hypoxaemia and hypercapnia at birth. However, term puppies clinically
      evolved more rapidly than preterm newborns. During the course of the study,
      premature neonates presented more severe complications, such as prolonged
      hypoxaemia and even death. In conclusion, premature puppies have no signs of
      immature enzymatic mechanisms for controlling oxidative stress, although SOD and
      GPx may participate in achieving acid-base balance. Aside from initial
      unremarkable symptoms, premature puppies should be carefully followed up, as they
      are at high risk of succumbing to odds of prematurity.

PMID- 25611796
TI  - County-level variation in prevalence of multiple chronic conditions among
      Medicare beneficiaries, 2012.

PMID- 25611798
TI  - Development of a nationally representative built environment measure of access to
      exercise opportunities.
AB  - We sought to develop a county-level measure to evaluate residents' access to
      exercise opportunities. Data were acquired from Esri, DeLorme World Vector
      (MapMart), and OneSource Global Business Browser (Avention). Using ArcGIS (Esri),
      we considered census blocks to have access to exercise opportunities if the
      census block fell within a buffer area around at least 1 park or recreational
      facility. The percentage of county residents with access to exercise
      opportunities was reported. Measure validity was examined through correlations
      with other County Health Rankings & Roadmaps' measures. Included were 3,114 of
      3,141 US counties. The average population with access to exercise opportunities
      was 52% (range, 0%-100%) with large regional variation. Access to exercise
      opportunities was most notably associated with no leisure-time physical activity
      (r = -0.47), premature death (r = -0.38), and obesity (r = -0.36). The measure
      uses multiple sources to create a valid county-level measure of exercise access.
      We highlight geographic disparities in access to exercise opportunities and call
      for improved data. 

PMID- 25611797
TI  - Spatial analysis and correlates of county-level diabetes prevalence, 2009-2010.
AB  - INTRODUCTION: Information on the relationship between diabetes prevalence and
      built environment attributes could allow public health programs to better target
      populations at risk for diabetes. This study sought to determine the spatial
      prevalence of diabetes in the United States and how this distribution is
      associated with the geography of common diabetes correlates. METHODS: Data from
      the Centers for Disease Control and Prevention and the US Census Bureau were
      integrated to perform geographically weighted regression at the county level on
      the following variables: percentage nonwhite population, percentage Hispanic
      population, education level, percentage unemployed, percentage living below the
      federal poverty level, population density, percentage obese, percentage
      physically inactive, percentage population that cycles or walks to work, and
      percentage neighborhood food deserts. RESULTS: We found significant spatial
      clustering of county-level diabetes prevalence in the United States; however,
      diabetes prevalence was inconsistently correlated with significant predictors.
      Percentage living below the federal poverty level and percentage nonwhite
      population were associated with diabetes in some regions. The percentage of
      population cycling or walking to work was the only significant built environment
      related variable correlated with diabetes, and this association varied in
      magnitude across the nation. CONCLUSION: Sociodemographic and built environment
      related variables correlated with diabetes prevalence in some regions of the
      United States. The variation in magnitude and direction of these relationships
      highlights the need to understand local context in the prevention and maintenance
      of diabetes. Geographically weighted regression shows promise for public health
      research in detecting variations in associations between health behaviors,
      outcomes, and predictors across geographic space.

PMID- 25611799
TI  - Coupled effects of applied load and surface structure on the viscous forces
      during peeling.
AB  - Tree frogs are able to take advantage of an array of epithelial cells in their
      toe pads to modulate their adhesion to surfaces under dry, wet, and flooded
      environments. It has been hypothesized that the interconnected channels
      separating the epithelial cells could reduce the hydrodynamic repulsion to
      facilitate contact under a completely submerged environment (flooded conditions).
      Using a custom-built apparatus we investigate the interplay between surface
      structure and loading conditions on the peeling force. By combining a normal
      approach and detachment by peeling we can isolate the effects of surface
      structure from the loading conditions. We investigate three surfaces: two rigid
      structured surfaces that consist of arrays of cylindrical posts and a flat
      surface as a control. We observe three regimes in the work required to separate
      the structured surface that depend on the fluid film thickness prior to pull out.
      These three regimes are based on hydrodynamics and our experimental results are
      compared with a simple scaling argument that relates the surface features to the
      different regimes observed. Overall we find that the work of separation of a
      structured surface is always less than or equal to that for a smooth surface when
      considering purely viscous contributions. 

PMID- 25611801
TI  - Mesenchymal stem cells transplantation for systemic lupus erythematosus.
AB  - Mesenchymal stem cells are a rare subset of stem cells residing in the bone
      marrow where they closely interact with hematopoietic stem cells and support
      their growth and differentiation. They can suppress proliferation or functions of
      many immune cells such as T cells, B cells, natural killer cells and dendritic
      cells. Recently, a substantial progress has been made in the field of mesenchymal
      stem cell transplantation. Experimental and clinical data suggest that this
      therapy has been a promising strategy for severe and refractory systemic lupus
      erythematosus. 

PMID- 25611802
TI  - Ideal colonoscopic surveillance intervals to reduce incidence of advanced adenoma
      and colorectal cancer.
AB  - BACKGROUND AND AIMS: There is limited information about the interplay between
      multiple risk factors contributing to the risk of advanced neoplasia. We
      determined the actual risk for advanced neoplasia in relation to lapsed time
      between colonoscopies in people enrolled in a structured surveillance program.
      This risk information can be used to guide the selection of optimal surveillance
      intervals. METHODS: Patients were recruited into programs at two major tertiary
      hospitals, with a personal or family history of advanced neoplasia. Five thousand
      one hundred forty-one patients had an index and one or more surveillance
      colonoscopies. Fifty-one percent had a family history of colorectal neoplasia
      while the remainder had a personal history. RESULTS: Patients with an immediately
      prior colonoscopy result (prior result) of advanced adenoma had a risk for
      advanced neoplasia 7.1 times greater than those with a normal prior result.
      Cancer as a prior result did not confer a greater risk than either a hyperplastic
      polyp or a nonadvanced adenoma. Being female reduced risk, age increased risk.
      Only a family history of a first-degree relative diagnosed under 55, or definite
      or suspected hereditary nonpolyposis colorectal cancer (HNPCC) conferred an
      increased risk over a personal history of advanced neoplasia. CONCLUSIONS: Most
      family history categories did not confer excess risk above personal history of
      advanced neoplasia. A prior cancer poses less of a risk than a prior advanced
      adenoma. Based on our models, a person with an advanced adenoma should be
      scheduled for colonoscopy at 3 years, corresponding to a 15% risk of advanced
      neoplasia for a male aged under 56. Guidelines should be updated that uses a 15%
      risk as a benchmark for calculating surveillance intervals.

PMID- 25611800
TI  - Evolutionary constraint and disease associations of post-translational
      modification sites in human genomes.
AB  - Interpreting the impact of human genome variation on phenotype is challenging.
      The functional effect of protein-coding variants is often predicted using
      sequence conservation and population frequency data, however other factors are
      likely relevant. We hypothesized that variants in protein post-translational
      modification (PTM) sites contribute to phenotype variation and disease. We
      analyzed fraction of rare variants and non-synonymous to synonymous variant ratio
      (Ka/Ks) in 7,500 human genomes and found a significant negative selection signal
      in PTM regions independent of six factors, including conservation, codon usage,
      and GC-content, that is widely distributed across tissue-specific genes and
      function classes. PTM regions are also enriched in known disease mutations,
      suggesting that PTM variation is more likely deleterious. PTM constraint also
      affects flanking sequence around modified residues and increases around clustered
      sites, indicating presence of functionally important short linear motifs. Using
      target site motifs of 124 kinases, we predict that at least ~180,000 motif
      breaker amino acid residues that disrupt PTM sites when substituted, and
      highlight kinase motifs that show specific negative selection and enrichment of
      disease mutations. We provide this dataset with corresponding hypothesized
      mechanisms as a community resource. As an example of our integrative approach, we
      propose that PTPN11 variants in Noonan syndrome aberrantly activate the protein
      by disrupting an uncharacterized cluster of phosphorylation sites. Further, as
      PTMs are molecular switches that are modulated by drugs, we study mutated binding
      sites of PTM enzymes in disease genes and define a drug-disease network
      containing 413 novel predicted disease-gene links. 

PMID- 25611803
TI  - Acute effect of an inhaled glucocorticosteroid on albuterol-induced
      bronchodilation in patients with moderately severe asthma.
AB  - BACKGROUND: We have previously shown that in patients with asthma a single dose
      of an inhaled glucocorticosteroid (ICS) acutely potentiates inhaled albuterol
      induced airway vascular smooth muscle relaxation through a nongenomic action. An
      effect on airway smooth muscle was not seen, presumably because the patients had
      normal lung function. The purpose of the present study was to conduct a similar
      study in patients with asthma with airflow obstruction to determine if an ICS
      could acutely also potentiate albuterol-induced airway smooth muscle relaxation
      in them. METHODS: In 15 adult patients with asthma (mean +/- SE baseline FEV1,
      62% +/- 3%), the response to inhaled albuterol (180 MUg) was assessed by
      determining the change in FEV1 (DeltaFEV1) for airway smooth muscle and in airway
      blood flow (DeltaQaw) for airway vascular smooth muscle measured 15 min after
      drug inhalation. Using a double-blind design, the patients inhaled a single dose
      of the ICS mometasone (400 MUg) or placebo simultaneously with or 30 min before
      albuterol inhalation. RESULTS: After simultaneous drug administration, mean
      DeltaFEV1 was 0.20 +/- 0.05 L (10%) after placebo and 0.32 +/- 0.04 L (19%) after
      mometasone (P < .05); mean DeltaQaw was -2% after placebo and 30% after
      mometasone (P < .005). When mometasone or placebo was administered 30 min before
      albuterol, there was a lesser and insignificant difference in DeltaFEV1 between
      the two treatments, whereas the difference in DeltaQaw remained significant.
      CONCLUSIONS: This pilot study showed that in adult patients with asthma with
      airflow obstruction, a single standard dose of an ICS can acutely increase the
      FEV1 response to a standard dose of inhaled albuterol administered
      simultaneously. The associated potentiation of albuterol-induced vasodilation in
      the airway was of greater magnitude and retained when the ICS was administered 30
      min before albuterol. The clinical significance of this observation will have to
      be established by a study involving a larger patient cohort. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01210170; URL: www.clinicaltrials.gov.

PMID- 25611804
TI  - Diabetes UK Position Statement. Competency frameworks in diabetes.
AB  - The quality, skills and attitudes of staff working in the healthcare system are
      central to multidisciplinary learning and working, and to the delivery of the
      quality of care patients expect. Patients want to know that the staff supporting
      them have the right knowledge and attitudes to work in partnership, particularly
      for conditions such as diabetes where 95% of all care is delivered by the person
      with diabetes themselves. With the current changes in the NHS structures in
      England, and the potential for greater variation in the types of 'qualified
      provider', along with the recent scandal at Mid-Staffordshire Hospital, staff
      need to be shown to be competent and named/accredited or recognized as such. This
      will help to restore faith in an increasingly devolved delivery structure. The
      education and validation of competency needs to be consistently delivered and
      assured to ensure standards are maintained for different roles and disciplines
      across each UK nation. Diabetes UK recommends that all NHS organizations
      prioritize healthcare professional education, training and competency through the
      implementation of a National Diabetes Competency Framework and the phased
      approach to delivery to address this need. 

PMID- 25611805
TI  - P38 and JNK signal pathways are involved in the regulation of phlorizin against
      UVB-induced skin damage.
AB  - Phlorizin is well known to inhibit sodium/glucose cotransporters in the kidney
      and intestine for the treatment of diabetes, obesity and stress hyperglycaemia.
      However, the effects of phlorizin against ultraviolet B (UVB) irradiation and its
      molecular mechanism are still unknown. We examined the effects of phlorizin on
      skin keratinocyte apoptosis, reactive oxygen species (ROS) production, pro
      inflammatory responses after UVB irradiation and the changes of some signal
      molecules by in vitro and in vivo assay. We observed that phlorizin pretreatments
      inhibited HaCaT cell apoptosis and overproduction of ROS induced by UVB.
      Phlorizin also decreased the expression of UVB-induced pro-inflammatory
      cytokines, such as interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and
      interleukin-8 (IL-8) at the mRNA level. Topical application of phlorizin on UVB
      exposed skin of nude mice prevented the formation of scaly skin and erythema,
      inhibited the increase of epidermal thickness and reduced acute inflammation
      infiltration in skin. Additionally, PCR, Western blot and immunohistochemical
      data showed that phlorizin reversed the overexpression of cyclooxygenase-2 (Cox
      2) induced by UVB irradiation both in vitro and in vivo. The activation of p38
      and JNK mitogen-activated protein kinases (MAPK) after UVB irradiation was also
      inhibited by phlorizin. These findings suggest that phlorizin is effective in
      protecting skin against UVB-induced skin damage by decreasing ROS overproduction,
      Cox-2 expression and the subsequent excessive inflammation reactions. It seemed
      that p38 and JNK MAPK signal pathways are involved in the regulation of the
      protective function of phlorizin. 

PMID- 25611806
TI  - Interferon regulatory factor 1 and histone H4 acetylation in systemic lupus
      erythematosus.
AB  - Histone acetylation modulates gene expression and has been described as increased
      in systemic lupus erythematosus (SLE). We investigated interferon regulatory
      factor 1 (IRF1) interactions that influence H4 acetylation (H4ac) in SLE.
      Intracellular flow cytometry for H4 acetylated lysine (K) 5, K8, K12, and K16 was
      performed. Histone acetylation was defined in monocytes and T cells from controls
      and SLE patients. RNA-Seq studies were performed on monocytes to look for an
      imbalance in histone acetyltransferases and histone deacetylase enzyme
      expression. Expression levels were validated using real-time quantitative RT-PCR.
      IRF1 induction of H4ac was evaluated using D54MG cells overexpressing IRF1. IRF1
      protein interactions were studied using co-immunoprecipitation assays. IRF1
      dependent recruitment of histone acetyltransferases to target genes was examined
      by ChIP assays using p300 antibody. Flow cytometry data showed significantly
      increased H4K5, H4K8, H4K12, and H4K16 acetylation in SLE monocytes. HDAC3 and
      HDAC11 gene expression were decreased in SLE monocytes. PCAF showed significantly
      higher gene expression in SLE than controls. IRF1-overexpressing D54MG cells were
      associated with significantly increased H4K5, H4K8, and H4K12 acetylation
      compared to vector-control D54MG cells both globally and at specific target
      genes. Co-immunoprecipitation studies using D54MG cells revealed IRF1 protein
      protein interactions with PCAF, P300, CBP, GCN5, ATF2, and HDAC3. ChIP
      experiments demonstrated increased p300 recruitment to known IRF1 targets in
      D54MG cells overexpressing IRF1. In contrast, p300 binding to IRF1 targets
      decreased in D54MG cells with IRF1 knockdown. SLE appears to be associated with
      an imbalance in histone acetyltransferases and histone deacetylase enzymes
      favoring pathologic H4 acetylation. Furthermore, IRF1 directly interacts with
      chromatin modifying enzymes, supporting a model where recruitment to specific
      target genes is mediated in part by IRF1.

PMID- 25611807
TI  - Luminescence of Eu and Ce in K3Ca2(SO4)3F fluoride material.
AB  - A new halophosphor K3Ca2(SO4)3F activated by Eu or Ce and K3Ca2(SO4)3F:Ce,Eu co
      doped halosulfate phosphor has been synthesized by the co-precipitation method
      and characterized for its photoluminescence (PL). The PL emission spectra of the
      K3Ca2(SO4)3F:Ce phosphor show emission at 334 nm when excited at 278 nm due to 5d
      -> 4f transition of Ce(3+) ions. In the K3Ca2(SO4)3F:Eu lattice, Eu(2+) (440 nm)
      as well as Eu(3+) (596 nm and 615 nm) emissions have been observed showing (5) D0
      ->(7) F1 and (5) D0 ->(7) F2 transition of the Eu(3+) ion, which is in the blue
      and red region of the visible spectrum respectively. The trivalent europium ion
      is very useful for studying the nature of metal coordination in various systems
      owing to its non-degenerate emitting (5) D0 state. K3Ca2(SO4)3F:Ce,Eu is suitable
      for Ce(3+) -> Eu(2+) -> Eu(3+) energy transfer in which Ce(3+) and Eu(2+) play
      the role of sensitizers and Eu(2+) and Eu(3+) act as the activators. The
      observations presented in this paper are relevant for lamp phosphors.

PMID- 25611808
TI  - Focused ultrasound of the pleural cavities and the pericardium by nurses after
      cardiac surgery.
AB  - OBJECTIVES: We aimed to study the feasibility and reliability of focused
      ultrasound (US) examinations to quantify pericardial (PE)- and pleural effusion
      (PLE) by a pocket-size imaging device (PSID) performed by nurses in patients
      early after cardiac surgery. DESIGN: After a 3-month training period, with
      cardiologists as supervisors, two nurses examined 59 patients (20 women) with US
      using a PSID at a median of 5 days after cardiac surgery. The amount of PE and
      PLE was classified in four categories by US (both) and chest x-ray (PLE only).
      Echocardiography, including US of the pleural cavities, by experienced
      cardiologists was used as reference. RESULTS: Focused US by the nurses was more
      sensitive than x-ray to detect PLE. The correlations of the quantification of PE
      and PLE by the nurses and reference was r (95% confidence interval) 0.76 (0.46
      0.89) and 0.81 (0.73-0.89), both p < 0.001. PE and PLE were drained in one and
      six (eight cavities) patients, all classified as large amount by the nurses.
      CONCLUSIONS: Cardiac nurses were able to obtain reliable measurements and
      quantification of both PE and PLE bedside by focused US and outperform the
      commonly used chest x-ray regarding PLE after cardiac surgery.

PMID- 25611811
TI  - Working "upstream": why we shouldn't use heterosexual women as health promotion
      change agents in HIV-prevention interventions aimed at heterosexual men.
AB  - The use of cognitive-behavioral interventions that aim to improve men's health
      seeking behaviors via women-a trend that grows increasingly troublesome as gender
      inequality persists-cannot address the deep-seated social, economic, and
      political inequalities contributing to the spread of HIV/AIDS, such as sexism and
      poverty. Such methods often rely on generalizations about men and women and
      regard female empowerment as a key goal, despite employing shaky definitions of
      the concept. Here we use the principles of health promotion, particularly
      determinants of health, to reflect upon and critique current interventions and
      present alternative programming models that engage both men and women in changing
      men's health-seeking behaviors and working "upstream" rather than "downstream" of
      the epidemic. 

PMID- 25611809
TI  - Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of
      colorectal cancer.
AB  - Fetuin-A, also referred to as alpha2-Heremans-Schmid glycoprotein (AHSG), is a
      liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible
      risk factor for colorectal cancer; however, the role of fetuin-A in the
      development of colorectal cancer is unclear. We investigated the association
      between circulating fetuin-A and colorectal cancer risk in a nested case-control
      study within the European Prospective Investigation into Cancer and Nutrition.
      Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367
      colorectal cancer cases and 1,367 matched controls. In conditional logistic
      regression models adjusted for potential confounders, the estimated relative risk
      (95% confidence interval) of colorectal cancer per 40 ug/mL higher fetuin-A
      concentrations (approximately one standard deviation) was 1.13 (1.02-1.24)
      overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for
      colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference
      in a Mendelian Randomization approach, five tagging single nucleotide
      polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control
      pairs. The AHSG allele-score explained 21% of the interindividual variation in
      plasma fetuin-A concentrations. In instrumental variable analysis, genetically
      raised fetuin-A was not associated with colorectal cancer risk (relative risk per
      40 ug/mL genetically determined higher fetuin-A was 0.98, 95% confidence
      interval: 0.73-1.33). The findings of our study indicate a modest linear
      association between fetuin-A concentrations and risk of colorectal cancer but
      suggest that fetuin-A may not be causally related to colorectal cancer
      development. 

PMID- 25611810
TI  - Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children
      in South Africa.
AB  - AIMS: Genetic factors, notably CYP2B6 516G->T [rs3745274] and 983T->C
      [rs28399499], explain much of the interindividual variability in efavirenz
      pharmacokinetics, but data from Africa are limited. We characterized
      relationships between genetic polymorphisms and plasma efavirenz concentrations
      in HIV-infected Black South African adults and children. METHODS: Steady-state
      mid-dosing interval efavirenz concentrations were measured. We genotyped 241
      polymorphisms in genes potentially relevant to efavirenz metabolism and
      transport, including ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3.
      RESULTS: Among 113 participants (59 adults and 54 children), minor allele
      frequencies for CYP2B6 516G->T, 983T->C, and 15582C->T [rs4803419] were 0.36,
      0.07, and 0.09, respectively. Based on composite CYP2B6 15582/516/983 genotype,
      there were 33 extensive metabolizer, 62 intermediate metabolizer and 18 slow
      metabolizer genotypes. Median (IQR) mid-dose efavirenz concentrations were 1.44
      (1.21-1.93) ug ml(-1), 2.08 (1.68-2.94) ug ml(-1) and 7.26 (4.82-8.34) ug ml(-1)
      for extensive, intermediate and slow metabolizers, respectively. In univariate
      analyses, a model that included composite genotype best predicted efavirenz
      concentrations (beta = 0.28, 95% CI 0.21, 0.35, P = 2.4 * 10(-11)). Among
      individual CYP2B6 polymorphisms, 516G->T best predicted efavirenz concentrations
      (beta = 0.22, 95% CI 0.13, 0.30, P = 1.27 * 10(-6)). There was also associations
      with 983T->C (beta = 0.27, 95% CI 0.10, 0.44, P = 0.002) and 15582C->T (beta =
      0.11, 95% CI 0.01, 0.22, P = 0.04). Associations were consistent in adults and
      children. No other polymorphisms were independently associated with efavirenz
      concentrations. CONCLUSIONS: Composite CYP2B6 genotype based on CYP2B6 516G->T,
      983T->C, and 15582C->T best described efavirenz exposure in HIV-infected Black
      South African adults and children.

PMID- 25611812
TI  - Nanostructured lipid carriers loaded with tributyrin as an alternative to improve
      anticancer activity of all-trans retinoic acid.
AB  - OBJECTIVES: All-trans retinoic acid (ATRA) is one of the most successful examples
      of differentiation agents and histone deacetylase inhibitors, such as tributyrin
      (TB), are known for their antitumor activity and potentiating action of drugs,
      such as ATRA. Nanostructured lipid carriers (NLC) represent a promising
      alternative to the encapsulation of lipophilic drugs such as ATRA. This study
      aims to develop, characterize and evaluate the cytotoxicity of ATRA-TB-loaded NLC
      for cancer treatment. METHODS: The influence of in situ formation of an ion
      pairing between ATRA and a lipophilic amine (benethamine) on the characteristics
      of NLC (size, zeta potential, encapsulation efficiency) was evaluated. TB, a
      butyric acid donor, was used as a component of the lipid matrix. In vitro
      activity on cell viability and distribution of cell cycle phases were evaluated
      for MCF-7, MDA-MB-231, HL-60 and Jurkat cell lines. RESULTS: The presence of the
      amine significantly increased the encapsulation efficiency of ATRA in NLC.
      Inhibition of cell viability by TB-ATRA-loaded NLC was more pronounced than the
      free drug. Analysis of the distribution of cell cycle phases also showed
      increased activity for TB-ATRA-loaded NLC, with the clear effect of cell cycle
      arrest in G0/G1 phase transition. The presence of TB played an important role in
      the activity of the formulation. CONCLUSION: Taken together, these findings
      suggest that TB-ATRA-loaded NLC represents a promising alternative to intravenous
      administration of ATRA in cancer treatment.

PMID- 25611815
TI  - Diffusion-weighted imaging in the characterization of breast lesions.

PMID- 25611813
TI  - Differentially regulated genes in the salivary glands of brown planthopper after
      feeding in resistant versus susceptible rice varieties.
AB  - Brown planthopper (BPH) is a damaging insect pest of rice. We used suppression
      subtractive hybridization (SSH) and mirror orientation selection to identify
      differentially regulated genes in salivary glands of BPH after feeding on
      resistant and susceptible varieties. The forward SSH library included 768 clones
      with insertions ranging from 250 to 1000 bp. After differential screening, a
      total of 112 transcripts were identified, which included 27 upregulated genes and
      seven downregulated genes. Several of these transcripts showed sequence homology
      to known proteins such as trehalase, mucin-like protein, vitellogenin, calcium
      ion binding protein, and eukaryotic initiation factor-like protein. About half of
      the transcripts, however, did not match to any sequences in the protein databases
      currently available. Functional annotation of the transcripts showed gene
      ontology association with metabolism, signal transduction, and regulatory
      responses. Notably, many known functional genes were predicted to be secreted
      proteins. Also, gene expression profiles of the salivary glands of BPH feeding on
      resistant rice (B5) and susceptible rice (TN1) varieties were compared. Our data
      provide a molecular resource for future functional studies on salivary glands and
      will be useful for elucidating the molecular mechanisms between BPH feeding and
      rice varieties with BPH resistance differences. 

PMID- 25611816
TI  - Toll-like receptor 5 in obesity: the role of gut microbiota and adipose tissue
      inflammation.
AB  - OBJECTIVE: This study aimed at establishing bacterial flagellin-recognizing toll
      like receptor 5 (TLR5) as a novel link between gut microbiota composition,
      adipose tissue inflammation, and obesity. METHODS: An adipose tissue microarray
      database was used to compare women having the highest (n = 4, H-TLR) and lowest
      (n = 4, L-TLR) expression levels of TLR5-signaling pathway genes. Gut microbiota
      composition was profiled using flow cytometry and FISH. Standard laboratory
      techniques were used to determine anthropometric and clinical variables. In vivo
      results were verified using cultured human adipocytes. RESULTS: The H-TLR group
      had higher flagellated Clostridium cluster XIV abundance and Firmicutes-to
      Bacteroides ratio. H-TLR subjects had obese phenotype characterized by greater
      waist circumference, fat %, and blood pressure (P < 0.05 for all). They also had
      higher leptin and lower adiponectin levels (P < 0.05 for both). Six hundred and
      sixty-eight metabolism- and inflammation-related adipose tissue genes were
      differentially expressed between the groups. In vitro studies confirmed that
      flagellin activated TLR5 inflammatory pathways, decreased insulin signaling, and
      increased glycerol secretion. CONCLUSIONS: The in vivo findings suggest that
      flagellated Clostridium cluster XIV bacteria contribute to the development of
      obesity through distorted adipose tissue metabolism and inflammation. The in
      vitro studies in adipocytes show that the underlying mechanisms of the human
      findings may be due to flagellin-activated TLR5 signaling.

PMID- 25611817
TI  - Arginine dipeptides affect insulin aggregation in a pH- and ionic strength
      dependent manner.
AB  - Solutions containing arginine or mixtures of arginine and other amino acids are
      commonly used for protein liquid formulations to overcome problems such as high
      viscosities, aggregation, and phase separation. The aim of this work is to
      examine whether the stabilizing properties of arginine can be improved by
      incorporating the amino acid into a dipeptide. A series of arginine-containing
      dipeptides have been tested for their ability to suppress insulin aggregation
      over a range of pH and ionic strength. The aggregation is monitored at room
      temperature using a combination of turbidimetry and light scattering for
      solutions at pH 5.5 or 3.7, whereas thermal-induced aggregation is measured at pH
      7.5. In addition, intrinsic fluorescence has been used to quantify additive
      binding to insulin. The dipeptide diArg is the most effective additive in
      solutions at pH 5.5 and 3.7, whereas the dipeptide Arg-Phe almost completely
      eliminates thermally-induced aggregation of insulin at pH 7.5 up to temperature
      of 90 degrees C. Insulin has been chosen as a model system because the molecular
      forces controlling its aggregation are well known. From this understanding, we
      are able to provide a molecular basis for how the various dipeptides affect
      insulin aggregation. 

PMID- 25611818
TI  - Hepatitis B outbreak in a nursing home associated with reusable lancet devices
      for blood glucose monitoring, Northern Germany 2010.
AB  - In September 2010, an outbreak of acute hepatitis B virus (HBV) infections in a
      nursing home was notified to public health authorities in Northern Germany. To
      identify the route of transmission and prevent further cases a retrospective
      cohort study was conducted. Blood samples of residents were tested for serologic
      markers of HBV infection and HBV subgenotypes and sequences were analyzed.
      Outbreak-related cases were defined as residents of the nursing home with
      detection of hepatitis B surface antigen (HBsAg) and the HBV DNA sequence of the
      outbreak strain in 2010. Information on possible risk factors as patient care,
      invasive diagnostic, and therapeutical procedures was collected using a
      standardized questionnaire. Risk ratios (RR) and 95% confidence intervals (CI)
      were estimated with exact Poisson regression and binomial regression. Sixty-four
      residents were included in the study, 5 of them were outbreak-related cases, 12
      had a past HBV infection. The outbreak strain belonged to HBV genotype D2 (HBsAg
      subtype ayw3, Ala118) which is not prevalent in Germany but in Eastern Europe.
      All cases (median age 81) were female, had diabetes, blood glucose monitoring,
      and chiropody. In multivariable analysis only blood glucose monitoring was
      associated with HBV infection (RR = 22, 95%CI 3.0-infinity). Blood glucose
      monitoring was reported to be done by nursing home staff with patient-based
      reusable lancet devices. In nursing home settings the use of single use lancets
      for blood glucose monitoring is recommended strongly to prevent transmission.
      National guidelines on the handling of point-of-care devices and reusable
      equipment in long-term care facilities should be developed.

PMID- 25611820
TI  - Engineered L-serine hydroxymethyltransferase from Streptococcus thermophilus for
      the synthesis of alpha,alpha-dialkyl-alpha-amino acids.
AB  - alpha,alpha-Disubstituted alpha-amino acids are central to biotechnological and
      biomedical chemical processes for their own sake and as substructures of
      biologically active molecules for diverse biomedical applications. Structurally,
      these compounds contain a quaternary stereocenter, which is particularly
      challenging for stereoselective synthesis. The pyridoxal-5'-phosphate (PLP)
      dependent L-serine hydroxymethyltransferase from Streptococcus thermophilus
      (SHMT(Sth); EC 2.1.2.1) was engineered to achieve the stereoselective synthesis
      of a broad structural variety of alpha,alpha-dialkyl-alpha-amino acids. This was
      accomplished by the formation of quaternary stereocenters through aldol addition
      of the amino acids D-Ala and D-Ser to a wide acceptor scope catalyzed by the
      minimalist SHMT(Sth) Y55T variant overcoming the limitation of the native enzyme
      for Gly. The SHMT(Sth) Y55T variant tolerates aromatic and aliphatic aldehydes as
      well as hydroxy- and nitrogen-containing aldehydes as acceptors.

PMID- 25611821
TI  - Designing new biocompatible glass-forming Ti75-x Zr10 Nbx Si15 (x = 0, 15)
      alloys: corrosion, passivity, and apatite formation.
AB  - Glass-forming Ti-based alloys are considered as potential new materials for
      implant applications. Ti75 Zr10 Si15 and Ti60 Zr10 Nb15 Si15 alloys (free of
      cytotoxic elements) can be produced as melt-spun ribbons with glassy matrix and
      embedded single beta-type nanocrystals. The corrosion and passivation behavior of
      these alloys in their homogenized melt-spun states have been investigated in
      Ringer solution at 37 degrees C in comparison to their cast multiphase
      crystalline counterparts and to cp-Ti and beta-type Ti-40Nb. All tested materials
      showed very low corrosion rates as expressed in corrosion current densities icorr
      < 50 nA/cm(2). Electrochemical and surface analytical studies revealed a high
      stability of the new alloys passive states in a wide potential range. This
      corresponds to low passive current densities ipass  = 2 +/- 1 uA/cm(2) based on
      the growth of oxide films with thickness d <10 nm. A homogeneous constituent
      distribution in the melt-spun alloys is beneficial for stable surface passivity.
      The addition of Nb does not only improve the glass-forming ability and the
      mechanical properties but also supports a high pitting resistance even at extreme
      anodic polarization up to 4V versus SCE were oxide thickness values of d ~35 nm
      are reached. With regard to the corrosion properties, the Nb-containing nearly
      single-phase glassy alloy can compete with the beta-type Ti-40Nb alloy. SBF tests
      confirmed the ability for formation of hydroxyapatite on the melt-spun alloy
      surfaces. All these properties recommend the new glass-forming alloys for
      application as wear- and corrosion-resistant coating materials for implants.

PMID- 25611822
TI  - Testosterone concentration and insulin sensitivity in young men with type 1 and
      type 2 diabetes.
AB  - OBJECTIVE: Reduced testosterone, a recognized comorbidity of reduced insulin
      sensitivity (IS) and type 2 diabetes (T2D), has also been reported in adult males
      with type 1 diabetes (T1D). However, there are limited data on how early reduced
      testosterone occurs, and whether it is related to the reduced IS in T1D. Leptin,
      a modulator of the HPG-axis, may also influence testosterone in T1D. We
      hypothesized that IS and leptin would be associated with total testosterone (TT),
      and free androgen index (FAI) in adolescent males with T1D. METHODS: T1D (n =
      35), T2D (n = 13), lean (n = 13) and obese (n = 9) adolescent males had IS
      measured by hyperinsulinemic-euglycemic clamps (glucose infusion rate [GIR]), in
      addition to leptin, sex hormone binding globulin (SHBG), TT, and FAI. The cohort
      was stratified into those with T1D (n = 35) and those without (n = 35). RESULTS:
      TT and SHBG were lower in T2D boys vs. lean controls, and GIR and leptin
      correlated with FAI and TT in non-T1D participants. However, despite being
      insulin resistant, adolescent males with T1D had normal TT and FAI, unrelated to
      GIR. In T1D, leptin was inversely associated with TT (p = 0.005) and FAI (p =
      0.01), independent of puberty, hemoglobin A1c (HbA1c), diabetes duration, body
      mass index (BMI) z-score and GIR. CONCLUSION: Leptin accounted for a significant
      proportion of the variability of testosterone in T1D. However, despite reduced
      IS, there was no association between IS and testosterone in T1D adolescents.
      These observations suggest that the mechanisms affecting testosterone may differ
      between adolescent males with and without T1D.

PMID- 25611823
TI  - A new regulatory mechanism for bacterial lipoic acid synthesis.
AB  - Lipoic acid, an essential enzyme cofactor, is required in three domains of life.
      In the past 60 years since its discovery, most of the pathway for lipoic acid
      synthesis and metabolism has been elucidated. However, genetic control of lipoic
      acid synthesis remains unclear. Here, we report integrative evidence that
      bacterial cAMP-dependent signaling is linked to lipoic acid synthesis in
      Shewanella species, the certain of unique marine-borne bacteria with special
      ability of metal reduction. Physiological requirement of protein lipoylation in
      gamma-proteobacteria including Shewanella oneidensis was detected using Western
      blotting with rabbit anti-lipoyl protein primary antibody. The two genes (lipB
      and lipA) encoding lipoic acid synthesis pathway were proved to be organized into
      an operon lipBA in Shewanella, and the promoter was mapped. Electrophoretic
      mobility shift assays confirmed that the putative CRP-recognizable site
      (AAGTGTGATCTATCTTACATTT) binds to cAMP-CRP protein with origins of both
      Escherichia coli and Shewanella. The native lipBA promoter of Shewanella was
      fused to a LacZ reporter gene to create a chromosome lipBA-lacZ transcriptional
      fusion in E. coli and S. oneidensis, allowing us to directly assay its expression
      level by beta-galactosidase activity. As anticipated, the removal of E. coli crp
      gene gave above fourfold increment of lipBA promoter-driven beta-gal expression.
      The similar scenario was confirmed by both the real-time quantitative PCR and the
      LacZ transcriptional fusion in the crp mutant of Shewanella. Furthermore, the
      glucose effect on the lipBA expression of Shewanella was evaluated in the
      alternative microorganism E. coli. As anticipated, an addition of glucose into
      media effectively induces the transcriptional level of Shewanella lipBA in that
      the lowered cAMP level relieves the repression of lipBA by cAMP-CRP complex.
      Therefore, our finding might represent a first paradigm mechanism for genetic
      control of bacterial lipoic acid synthesis.

PMID- 25611824
TI  - Inclusion of ecologically based trait variation in plant functional types reduces
      the projected land carbon sink in an earth system model.
AB  - Earth system models demonstrate large uncertainty in projected changes in
      terrestrial carbon budgets. The lack of inclusion of adaptive responses of
      vegetation communities to the environment has been suggested to hamper the
      ability of modeled vegetation to adequately respond to environmental change. In
      this study, variation in functional responses of vegetation has been added to an
      earth system model (ESM) based on ecological principles. The restriction of
      viable mean trait values of vegetation communities by the environment, called
      'habitat filtering', is an important ecological assembly rule and allows for
      determination of global scale trait-environment relationships. These
      relationships were applied to model trait variation for different plant
      functional types (PFTs). For three leaf traits (specific leaf area, maximum
      carboxylation rate at 25  degrees C, and maximum electron transport rate at 25 
      degrees C), relationships with multiple environmental drivers, such as
      precipitation, temperature, radiation, and CO2 , were determined for the PFTs
      within the Max Planck Institute ESM. With these relationships, spatiotemporal
      variation in these formerly fixed traits in PFTs was modeled in global change
      projections (IPCC RCP8.5 scenario). Inclusion of this environment-driven trait
      variation resulted in a strong reduction of the global carbon sink by at least
      33% (2.1 Pg C yr(-1) ) from the 2nd quarter of the 21st century onward compared
      to the default model with fixed traits. In addition, the mid- and high latitudes
      became a stronger carbon sink and the tropics a stronger carbon source, caused by
      trait-induced differences in productivity and relative respirational costs. These
      results point toward a reduction of the global carbon sink when including a more
      realistic representation of functional vegetation responses, implying more carbon
      will stay airborne, which could fuel further climate change. 

PMID- 25611825
TI  - Therapist awareness of client resistance in cognitive-behavioral therapy for
      generalized anxiety disorder.
AB  - Clients' resistance relates negatively to their retention and outcomes in
      psychotherapy; thus, it has been increasingly identified as a key process marker
      in both research and practice. This study compared therapists' postsession
      ratings of resistance with those of trained observers in the context of 40
      therapist-client dyads receiving 15 sessions of cognitive-behavioral therapy for
      generalized anxiety disorder. Therapist and observer ratings were then examined
      as correlates of proximal (therapeutic alliance quality and homework compliance)
      and distal (posttreatment worry severity) outcomes. Although there was reasonable
      concordance between rater perspectives, observer ratings were highly and
      consistently related to both proximal and distal outcomes, while therapist
      ratings were not. These findings underscore the need to enhance therapists'
      proficiency in identifying important and often covert in-session clinical
      phenomena such as the cues reflecting resistance and noncollaboration. 

PMID- 25611826
TI  - Increased yield of exome sequencing by off-target mitochondrial DNA analysis.

PMID- 25611827
TI  - Upper-Extremity Physical-Performance Tests in College Athletes.
AB  - CONTEXT: Physical-performance tests (PPTs) are commonly used in rehabilitation
      and injury-prevention settings, yet normative values of upper-extremity PPTs have
      not been established in high-level athletes. OBJECTIVE: To establish normative
      data values for the Closed Kinetic Chain Upper-Extremity Stability Test (CKCUEST)
      and Upper-Quarter Y-Balance Test (UQYBT) in college athletes and compare results
      between sports and to analyze the relationship between the 2 tests. DESIGN:
      Observational. SETTING: Laboratory/athletic facility. PARTICIPANTS: 257 (118
      male, 139 female) Division I athletes participating in basketball, soccer,
      baseball, lacrosse, volleyball, track and field, and cross-country. INTERVENTION:
      CKCUEST and UQYBT scores were recorded as part of a comprehensive injury-risk
      screening battery. MAIN OUTCOME MEASURE: Pearson correlations assessed the
      relationship between all measures of the CKCUEST and UQYBT. A factorial ANOVA and
      a repeated-measures ANOVA (arm dominance) were used to assess interactions
      between sex, year in school, and sport for CKCUEST and UQYBT scores. RESULTS:
      Normative values for the CKCUEST and UQYBT were established for 9 men's and
      women's college sports. No significant relationships were found between PPT
      scores. Men scored significantly higher than women for the CKCUEST (P = .002) and
      UQYBT (P = .010). Baseball players scored significantly higher than athletes from
      all other sports for the UQYBT (P < .001) but showed nonsignificant trends of
      lower scores for the CKCUEST than lower-extremity-dominant athletes such as
      runners (P = .063) and lacrosse players (P = .058). CONCLUSIONS: Results suggest
      that average CKCUEST and UQYBT scores in Division I athletes are distinct from
      those previously reported in recreationally active populations and that
      performance differences exist between sexes and sports. In addition, the CKCUEST
      and UQYBT appear to measure different constructs of performance and may
      complement each other as part of a screening battery.

PMID- 25611828
TI  - Home haemodialysis in Spain.

PMID- 25611829
TI  - When should a nephrologist suspect a mitochondrial disease?
AB  - Mitochondrial diseases, taking into account those that affect the processes of
      the respiratory chain (RC) and mitochondrial oxidative phosphorylation system
      (OXPHOS), make up a relatively frequent group within rare diseases that usually
      have multisystem involvement, a very variable phenotypic expression and a complex
      genetic base. Renal involvement is uncommon, with the tubule being the most
      affected, specifically its proximal portion, developing into full Toni
      Debr&eacute;-Fanconi syndrome in the most serious cases. However, in some cases
      the glomerulus is involved, fundamentally in focal segmental glomerulosclerosis
      form (FSGS), expressed by proteinuria and renal failure. It is important that the
      Nephrologist keeps in mind the possibility of a mitochondrial disease in patients
      with this type of renal involvement that present clinical data with these
      characteristics, especially diabetes mellitus and deafness. In cases with FSGS, a
      correct diagnosis will avoid the inappropriate use of immunosuppressive
      medication. Specific treatments do not exist for the majority of mitochondrial
      diseases, but it is likely that the intense research that currently exists for
      these diseases will eventually produce effective treatment possibilities. 

PMID- 25611830
TI  - Mortality on a renal transplantation waiting list.
AB  - Renal transplantation (Tx) represents the treatment of choice for patients with
      advanced chronic kidney disease (ACKD), but the shortage of available organs for
      those with a high level of comorbidity can significantly increase mortality in
      patients who are candidates for Tx. This constitutes a worrying health care
      problem, given the increase in incident and prevalent patients with ACKD, and is
      especially concerning amongst those with ACKD that is secondary to conditions
      with a high level of comorbidity, such as diabetes or arterial hypertension. In
      addition, this can increase the number of patients on the waiting list (WL) and
      cause the rapid raising of mortality figures. Therefore, nowadays it is relevant
      to identify the causes of death and the mortality risk factors in this
      population, to know the barriers that limit access to Tx and to apply predictive
      mortality models, with the aim of improving survival rates from these illnesses.
      In this review on the mortality of the patients on the WL, the following aspects
      will be addressed: 1) the magnitude of this problem and the importance of certain
      epidemiological data; 2) the mortality risk factors in these patients and the
      barriers that exist against access to Tx, which could increase mortality rates
      amongst this population; 3) evaluation of the risk of death in patients on
      dialysis from comorbidity; 4) assessment of mortality on the WL, via regression
      analysis of competitive risks, and the generation of a compound risk model, which
      includes comorbidity and other uraemic factors. 

PMID- 25611831
TI  - Vitamin D, vitamin D receptor and the importance of its activation in patients
      with chronic kidney disease.
AB  - Vitamin D deficiency has been linked to many different pathologies, especially
      with morbimortality in patients with chronic kidney disease. The progressive loss
      of renal function leads to calcitriol deficiency and homeostatic changes in
      calcium, phosphorus, FGF-23 and PTH, among others. All these changes can also
      influence vitamin D receptor (VDR) activation and the development of secondary
      hyperparathyroidism (SHPT). The biologic actions of both vitamin D and its
      synthetic analogues are mediated by binding to the same VDR, acting on different
      genes. There is a narrow relationship between low levels of calcitriol and SHPT.
      The combined approach of VDR activation and phosphate restriction, among others,
      plays an important role in the early treatment of the chronic kidney disease
      mineral and bone disorder (CKD-MBD). The Spanish Society of Nephrology, in order
      to reduce the uniform and significant association with CKD-associated mortality,
      calcidiol and high phosphate levels suggests normalization of phosphate as well
      as calcidiol levels in both CKD and dialysis patients. Moreover, it considers
      that, in addition to selective/non selective activation of VDR for the prevention
      and treatment of SHPT, VDR could be activated in dialysis patients by native
      vitamin D or even low paricalcitol doses, independently of PTH levels, as some
      cohort studies and a recent metaanalysis have found an association between
      treatment with active vitamin D and decreased mortality in patients with CKD. In
      general it is considered reasonable to use all this information to individualise
      decision making. 

PMID- 25611832
TI  - Malignant hypertension: a type of IgA nephropathy manifestation with poor
      prognosis.
AB  - INTRODUCTION:  Malignant hypertension (MHT) is an uncommon clinical manifestation
      of IgA Nephropathy (IgAN). Its prevalence, pathogenesis and evolution are not
      well known.  MATERIAL AND METHODS:  We performed a descriptive and retrospective
      study to report the clinical characteristics and evolution of thirteen patients
      diagnosed as having IgA nephropathy by renal biopsy in our hospital who developed
      MHT (IgAN-MHT).  RESULTS:  The prevalence of MHT in our IgAN patients was 7%
      (13/186). The mean age was 37&plusmn;12 years and 84% were males. Mean
      systolic/diastolic blood pressure at presentation were
      219&plusmn;32/132&plusmn;18mmHg, respectively. Renal function impairment was
      detected at admission in all the patients, with a mean serum creatinine of
      4.73&plusmn;3.12mg/dL. No patient showed analytical data that suggested
      thrombotic microangiopathy. Renal biopsies showed mild chronicity lesions and
      only four patients presented features of thrombotic microangiopathy. All patients
      were treated with renin-angiotensin-aldosterone blockers and two received
      steroids. They all showed a progressive loss of renal function. At the end of
      follow up one patient had died, ten were on chronic dialysis and two presented
      chronic kidney disease stage 3b. Renal survival was 69% and 35% at 3 and 6 years,
      respectively. Six patients received a kidney transplant: IgAN relapsed in four
      patients. One of them presented a new episode of MHT associated with a HELLP
      syndrome.  CONCLUSIONS:  Malignant hypertension is a form of IgAN clinical
      presentation having a remarkably worse renal outcome and without specific
      effective treatment.

PMID- 25611833
TI  - On-line haemodiafiltration with auto-substitution: assessment of blood flow
      changes on convective volume and efficiency.
AB  - INTRODUCTION: On-line haemodiafiltration (OL-HDF) is currently the most effective
      technique and several randomised studies and meta-analyses have seen a reduction
      in mortality and an association directly related with convective volume is
      observed. Blood flow (Qb) limits the infusion rate to 25-33 % and is the main
      limiting factor for reaching an optimum substitution volume. With the recent
      incorporation of monitors with auto-substitution systems, the aim of the study
      was to assess the effect of Qb variations on convective volume and purifying
      capacity. MATERIAL AND METHODS: 23 patients, 17 men and 6 women, were included,
      with an average age of 65.5 &plusmn;10 years, time on dialysis 292.2 &plusmn; 15
      minutes, which were in the OL-HDF programme with the 5008 Cordiax monitor with
      auto-substitution. Each patient was analysed over 5 sessions in which only the Qb
      was changed (250, 300, 350, 400 and 450 ml/min). In each session the substitution
      volume, total convective volume and parameters of dialysis were measured. The
      concentration of urea (60 Da), creatinine (113 Da), &beta;2-microglobulin (11,800
      Da), myoglobin (17,200 Da), prolactin (23,000 Da), &alpha;1-microglobulin (33,000
      Da) and &alpha;1-acid glycoprotein (40,000 Da) in plasma was measured at the
      start and end of each session in order to calculate the percentage of reduction
      of these solutes. RESULTS: The trans-membrane pressure was less, with Qb 250
      ml/min. A significant increase in convective volume was observed with the
      increase in Qb, 23.7, 26.9, 30.2, 32.8 and 35.2 l/session to 250, 300, 350, 400
      and 450 ml/min, respectively (P < 0.001), representing a percentage of total
      purified blood of 33.2, 31.2, 30.2, 28.7 and 27.3 % respectively. The percentages
      of reduction of urea and creatine progressively increased with Qb, slight
      differences were observed with &beta;2-microglobulin and myoglobin, and no
      changes were observed in the larger molecules. CONCLUSION: For each 50 ml/min
      increase in Qb, the convective volume increased by between 8 and 12 ml/min. The
      auto-substitution system strengthens the lowest Qbs in the percentage of
      convective volume with regards to total purified blood. Qb increases the
      purifying capacity of small molecules, favouring that of &beta;2-microglobulin
      and myoglobin, and does not influence molecules of a greater molecular weight. 

PMID- 25611834
TI  - Arterial stiffness in kidney transplantation: a single center case-control study
      comparing belatacept versus calcineurin inhibitor immunosuppressive based
      regimen.
AB  - Arterial stiffness is nowadays a well-accepted predictor of cardiovascular
      mortality in general population; as well as in kidney transplant recipient
      population. The femoral-carotid pulse wave velocity (cf-PWV) is the widest used
      method to assess the arterial stiffness. The aim of this study was to test
      whether CNI-free immunosuppression based on belatacept was associated with lower
      cf-PWV, as a surrogate marker of arterial stiffness, than CNI. This was a
      retrospective case-control study. We included all the cases treated with
      belatacept as a maintenance immunosuppression in our center (n=20). An
      appropriate control group of patients (n=20) treated with CNI was selected to
      achieve match for key factors associated with arterial stiffness. After a follow
      up of 5 years after transplantation, the Belatacept group had a reduced
      prevalence of patients with a cf-PWV higher than 8.1m/s (50% in BLC vs. 25% in
      CNI, p=0.08). At multivariate logistic regression analysis, the risk of high cf
      PWV was correlated with age (OR 1.24; p<0.03) and renal resistive index (OR 1.25;
      p<0.05). Belatacept treatment was associated with a significant reduction in risk
      of cf-PWV (OR 0.008; P=0.045). Belatacept-based maintenance immunosuppression
      could improve kidney transplant recipient&rsquo;s survival by reducing
      cardiovascular events related to stiffness. 

PMID- 25611835
TI  - Water renal management is altered more frequently than albuminuria in children in
      the G1 stage of the 2012 KDIGO Guideline.
AB  - BACKGROUND: The G1 stage of chronic kidney disease (CKD) is defined in the 2012
      KDIGO Guideline as kidney damage characterized by structural or functional kidney
      abnormalities without deterioration of glomerular filtration rate. Albuminuria
      and electrolyte abnormalities due to tubular disorders are considered functional
      markers of kidney damage. Changes in renal water handling are not explicitly
      cited in these guidelines. A large sample of children with abnormal
      dimercaptosuccinic acid (DMSA) scan located in the G1 stage was used in this
      study. METHODS: Ambispective, cross-sectional study to evaluate the clinical
      histories of 116 pediatric patients. 100 patients were included in the first
      group (G1 stage) and 16 patients in the G2-G5 stages according to the
      classification of CKD Guideline KDIGO. All the patients had a renal pathologic
      DMSA scan. GFR, maximum urine osmolality and albumin/creatinine and
      NAG/creatinine ratios were determined. RESULTS: The patients with normal GFR, in
      relation to those with reduced GFR, had significantly higher values of maximum
      urine osmolality and significantly reduced values of urine volume and
      albumin/creatinine and NAG/creatinine ratios. The most frequently observed
      alterations in children in the KDIGO G1 stage were those involving the water
      renal management such as urinary concentrating ability defect (29%) and increased
      urinary volume (20%). The frequency of children with increased urinary
      elimination of albumin (12%) and NAG (3%) was more lower. All children in KDIGO
      G2-G5 stages had alterations in water renal management. CONCLUSIONS: The
      parameters related with the water renal management are affected more frequently
      than albumin urinary excretion in children who have loss of parenchyma and normal
      GFR.

PMID- 25611836
TI  - Relation between serum cathepsin D levels and endothelial dysfunction in patients
      with chronic kidney disease.
AB  - We aimed to investigate the role of cathepsin D, an inflammatory and
      atherosclerotic mediator, in endothelial dysfunction in chronic kidney disease.
      The study included 65 patients with stage 2&ndash;4 chronic kidney disease (35
      females, 30 males; mean age, 55.8&plusmn;15.6 years). Serum creatinine and
      cathepsin D levels and glomerular filtration rates (GFRs) were determined, and
      brachial flow-mediated dilation (FMD) percentage was measured by two-dimensional
      gray scale and color flow Doppler and vascular imaging. FMD &le;6% was considered
      to indicate endothelial dysfunction. Mean GFR, median creatinine levels, and
      median cathepsin D levels were 40.2&plusmn;11.2mL/min/1.73m2, 1.7mg/dL, and
      819.75ng/mL, respectively. Endothelial dysfunction was present in 30 of the 65
      patients (46.2%). There was a significant difference between groups with and
      without endothelial dysfunction in terms of cathepsin D (p=0.001) and creatinine
      (p=0.03) levels, and negative and significant correlations were found between
      brachial artery FMD% and cathepsin D (r=&minus;0.359, p=0.003) and creatinine
      (r=&minus;0.304, p=0.014) levels. Cathepsin D, which is known to be associated
      with atherosclerosis, may play a role in the process of endothelial dysfunction.
      Further studies are essential to determine the exact function of cathepsin D in
      endothelial dysfunction in chronic kidney disease and to determine its value as a
      tool for early diagnosis and target for treatment of cardiovascular diseases in
      patients with chronic kidney disease. 

PMID- 25611837
TI  - Neoplasm in kidney graft. Analysis of the cause of the tumour and treatment
      options.
AB  - Kidney transplant is the treatment of choice for chronic kidney disease.
      Cardiovascular disease, infections, and postransplant de novo neoplasms are the
      main causes of death in transplant patients. The most frequent kind of post
      kidney transplant neoplasms are lymphoproliferative processes and cutaneous
      neoplasms. Another type of neoplasm, that of kidney tumours, also represents
      approximately 3% of all neoplasms in transplant patients. A review of the kidney
      transplants from our unit performed between July 1985 and October 2012 which
      presented a mass in the kidney graft was carried out, confirming the diagnosis by
      taking a biopsy of the mass. In all the cases, the underlying pathology, kidney
      function and immunosuppressive treatment were analysed. This article aims to give
      importance to monitoring and management of the appearance of possible tumour
      masses in kidney transplants. 

PMID- 25611838
TI  - Review of studies on health related quality of life in patients with advanced
      chronic kidney disease in Spain.
AB  - BACKGROUND: Advanced chronic kidney disease (ACKD) has a great impact on health
      related quality of life (HRQL). The use of this variable in studies in our field
      is becoming more frequent, although there has been no comprehensive review of how
      Spaniards with ACKD are assessed. AIMS: To offer a contrasted vision of the HRQL
      assessment tools that are most often used on Spanish ACKD population, also
      analysing how this population perceive their quality of life. METHOD: A review
      was carried out on literature published on studies undertaken in Spain that had
      used some kind of instrument, either generic or specific, in order to measure
      HRQL in patients with different stages of ACKD. Studies in kidney transplant
      patients were excluded when they were independently reviewed. The research was
      carried out in CINAHL, CUIDEN, DOCUMED, EMBASE, ERIC (USDE), IME, LILACS,
      MEDLINE, Nursin@ovid, PubMed, Scielo, Web of Science and TESEO. RESULTS: 53
      articles published between 1995 and May 2014 have been included in this review.
      Renal replacement therapy is the variable that is most often associated with the
      study of HRQL, with haemodialysis being the most studied. Most of the studies
      found are cross-sectional and the Short Form-36 Health Survey is the most used
      instrument. CONCLUSIONS: The majority of the studies show how HRQL is
      significantly affected in patients who receive renal replacement therapy. These
      results are independent from the instrument used to measure health-related
      quality of life and other associated variables throughout the various studies.
      HRQL has been particularly analysed in patients on haemodialysis, using mainly
      observational methods and the Short Form-36 Health Survey. There is a need for
      more studies that address aspects such as HRQL in the pre-dialysis phase, as well
      as studies with larger samples and longitudinal, analytical and experimental
      designs.

PMID- 25611839
TI  - Juxtaglomerular cell tumour as a curable cause of hypertension: case
      presentation.
AB  - Arterial hypertension is a highly prevalent disease and its secondary causes must
      always be kept in mind because the treatment and prognosis differ between these
      and essential hypertension. Here we present the first reported case in Argentina
      of a 21-year-old patient with arterial hypertension and hypokalaemia due to a
      renin-secreting juxtaglomerular cell tumour, which was diagnosed after seven
      years of development. 

PMID- 25611840
TI  - Comment on "Cost analysis and sociocultural profile of kidney patients. Impact of
      the treatment method".

PMID- 25611841
TI  - Response to the comment on "Cost analysis and sociocultural profile of kidney
      patients. Impact of the treatment method".

PMID- 25611842
TI  - Comment on "Management of hypercalcemia after renal transplantation".

PMID- 25611843
TI  - Comment on "A smaller proportion of circulating biologically active parathyroid
      hormone in peritoneal dialysis does not allow inter-method adjustment of
      established parathyroid hormone for haemodialysis".

PMID- 25611844
TI  - Development and use of an application programming interface modified from
      GoogleMaps(c) for the georeferencing of patients with glomerular disease.

PMID- 25611845
TI  - Peritoneal dialysis allows successful cardiac transplantation in patients with
      refractory heart failure.

PMID- 25611846
TI  - Restoration of Train-of-Four Ratio with Neostigmine After Insufficient Recovery
      with Sugammadex in a Patient with Myasthenia Gravis.
AB  - We present a patient with myasthenia gravis in whom sugammadex failed to restore
      the train-of-four ratio (TOFR) sufficiently. When the patient's TOFR count had
      recovered to 2, we administered 2 mg/kg of sugammadex. However, the TOFR did not
      recover to the preoperative value. An additional 2 mg/kg of sugammadex also had
      no effect. We then administered 30 MUg/kg of neostigmine which restored the TOFR
      to more than the preoperative value. We speculate that exacerbation of myasthenia
      symptoms during surgery interfered with recovery of TOFR after sugammadex
      administration. 

PMID- 25611847
TI  - Prolonged respiratory depression after general anesthesia in an adult with
      congenital rubella syndrome.
AB  - Congenital rubella syndrome (CRS) is caused by rubella virus infection of the
      pregnant mother leading to teratogenic effects on the fetus. Although rare in the
      developed world, manifestations reach far into adulthood and underscore the
      importance of careful evaluation before surgery. We present a case of an adult
      with CRS in whom unexpected prolonged postoperative respiratory depression
      occurred. Perioperative workup of CRS and investigations pertaining to the
      patient's respiratory insufficiency are discussed. 

PMID- 25611849
TI  - Intraoperative Bronchopleural Fistula During Thoracoscopic Lobectomy: The Role of
      End-Tidal CO2 Monitoring.
AB  - Video-assisted thoracoscopic surgery has become a common procedure in pediatric
      surgery. We present a case of accidental intraoperative bronchopleural fistula
      during a video-assisted thoracoscopic surgery procedure, which was first
      identified by the anesthesia team. We discuss differential diagnoses including
      the role of end-tidal carbon dioxide monitoring as an aid to prompt diagnosis. 

PMID- 25611848
TI  - Immunoglobulin e-mediated anaphylaxis on the tenth exposure to cisatracurium in a
      4-year-old child.
AB  - A 4-year-old female developed hypotension, tachycardia, hypoxemia, and diffuse
      erythema after induction of anesthesia with ketamine, fentanyl, and
      cisatracurium. Treatment consisted of repeated doses of epinephrine,
      diphenhydramine, corticosteroids, and IV fluids. Skin prick testing performed 4
      weeks after the incident confirmed an immunoglobulin E-mediated anaphylaxis to
      cisatracurium. She had 8 previous exposures to cisatracurium without incident.
      She had experienced hypotension on the ninth exposure to cisatracurium but the
      decrease in arterial blood pressure was attributed to propofol. On the tenth
      exposure to cisatracurium, the patient developed evidence of anaphylactic shock
      that led to the diagnosis. 

PMID- 25611850
TI  - Point-of-care testing in critically ill patients.
AB  - Point-of-care (POC) testing in hemostasis has experienced a significant increase
      in the spectrum of available tests and the number of tests performed. Short turn
      around time and observation of rapid changes in test results are facilitated. The
      quality control process in POC testing must encompass a preanalytic (collection),
      analytic (measurement), and postanalytic (clinical response) phase. Erroneous
      interpretation of findings and difficult quality controls can outweigh the
      advantages of POC testing.Only a limited number of hemostatic POC tests have
      proven useful so far: prothrombin time POC-monitoring of oral vitamin K
      antagonists; activated clotting time POC-monitoring of high-dose heparin therapy;
      platelet function analyzer (PFA; Siemens, Marburg, Germany) closure time (CT)
      detection of von Willebrand disease and severe platelet function defects; whole
      blood aggregometry (WBA) Multiplate (Roche Diagnostics, Rotkreuz, Switzerland),
      and the VerifyNow system (Accumetrics, San Diego, CA)-detection of platelet
      dysfunction due to antiplatelet drugs; thromboelastography-continuous observation
      of clot formation and fibrinolysis. The use of various agonists in WBA and
      thromboelastography (TEG) requires some expertise. In experienced hands the PFA
      CT and WBA and TEG are recommended combinations.Application of POC testing
      depends strictly on whether it improves medical care and patient outcome. More
      POC test systems are in the research pipeline, but only a few will resist the
      ravages of time. 

PMID- 25611851
TI  - Restriction fragment length polymorphism effectively identifies exon 1 mutation
      of UGT1A1 gene in patients with Gilbert's Syndrome.
AB  - BACKGROUND & AIMS: Gilbert's syndrome causes pharmacological variation in drug
      glucuronidation and unexpected toxicity from therapeutic agents. The two common
      genotypes of Gilbert's syndrome are a dinucleotide polymorphism (TA)7 in TATA-Box
      as well as the 211G>A mutation in the coding exon 1, particularly in Asians, of
      human UGT1A1 gene. In this study, we aimed to establish an effective method to
      detect the 211G>A mutation. METHODS: The coding exon 1 sequence of human UGT1A1
      gene was analysed by Vector NTI software. The 211G>A mutation in the coding exon
      1 of UGT1A1 gene was determined by restriction fragment length polymorphism
      (RFLP) method. Serum total bilirubin level was measured as well. RESULTS: A newly
      identified BsmBI site was located in the coding exon 1 of UGT1A1 gene. The 211G>A
      mutation in the coding exon 1 of UGT1A1 gene was determined by DNA RFLP.
      Furthermore, we reported our present work on genetic analysis of mutations of
      UGT1A1 gene, and the correlation of UGT1A1 mutations with serum total bilirubin
      levels in Taiwanese population. The results showed that 15 subjects carried
      211G>A mutation in 23 subjects related with Gilbert's syndrome. The homozygous
      211G>A mutant as well as simultaneously heterozygous mutants both in TATA-Box and
      211G>A significantly increased the risk of Gilbert's syndrome similar to subjects
      carrying homozygous TATA-Box mutant. CONCLUSIONS: BsmBI RFLP is an effective
      method to detect 211G>A mutation in the coding exon 1 of UGT1A1 gene. The common
      211G>A mutation is one of the causes of Gilbert's syndrome in Taiwanese
      population.

PMID- 25611852
TI  - A simple strategy for synthesizing highly luminescent carbon nanodots and
      application as effective down-shifting layers.
AB  - We propose a novel strategy to prepare highly luminescent carbon nanodots (C
      dots) by employing a hydrothermal method with citric acid as the carbon source
      and ethylenediamine as the nitrogen source, together with adding moderate ammonia
      water (AW) to achieve both appropriate inner structure and excellent N
      passivation. The effect of pH value and AW amount on the luminescence properties
      has been thoroughly investigated. The photoluminescence quantum yield of the
      resultant C-dots reaches as high as 84.8%, which is of 10.56% higher than that of
      the C-dots synthesized in the absence of AW in the reaction precursors. We have
      further combined the highest luminescent C-dots with polyvinyl alcohol to form
      luminescent down-shifting layers on silicon nanowire solar cells. An effective
      enhancement of short-circuit current density has been realized and the
      contribution of the down-shifting has been extracted quantitatively from the
      deterioration of surface reflectance and the gain of the optical absorption
      redistribution by means of a theoretical model on external quantum efficiency
      analysis. 

PMID- 25611853
TI  - Metabolic change in the right dorsolateral prefrontal cortex and its correlation
      with symptom severity in patients with generalized anxiety disorder: Proton
      magnetic resonance spectroscopy at 3 Tesla.
AB  - AIMS: A few neuroimaging studies have demonstrated the key brain areas associated
      with generalized anxiety disorder (GAD). However, the brain metabolic changes in
      the dorsolateral prefrontal cortex (DLPFC) of patients with GAD are unclear. This
      study utilized 3-Tesla proton magnetic resonance spectroscopy ((1) H-MRS) to
      assess the DLPFC metabolic change and its correlation with symptom severity in
      patients with GAD. METHODS: Patients with GAD diagnosed using the DSM-IV-TR and
      age-matched healthy controls participated in this study. Brain metabolite
      concentrations were measured from a localized voxel on the DLPFC using 3-Tesla
      (1) H-MRS. Also, the volumetric composition of the gray matter and white matter
      volumes was assessed using voxel-based morphometry. RESULTS: The choline/creatine
      and choline/N-acetylaspartate ratios were significantly lower in patients than in
      controls. However, there were no significant differences in other metabolite
      ratios between the two groups. Choline concentrations were negatively correlated
      with anxiety levels as measured by the Hamilton Anxiety Rating Scale and the
      Generalized Anxiety Disorder Scale 7. There was no significant difference in the
      gray matter and white matter volumes in the MRS voxel between the two groups.
      CONCLUSIONS: The present study demonstrates that GAD is associated with low a
      level of choline/N-acetylaspartate in the DLPFC, which is closely related with
      symptom severity and cognitive dysfunction. This finding will be useful for an
      understanding of the neural mechanism associated with GAD.

PMID- 25611854
TI  - Negative life events and attempted suicide in rural China.
AB  - OBJECTIVE: This study aimed to examine the association between negative life
      events (NLEs) and attempted suicide in rural China. METHODS: Six rural counties
      were selected from disease surveillance points in Shandong province, China. A
      total of 409 suicide attempters in rural areas between October 1, 2009, and March
      31, 2011, and an equal number of matched controls were interviewed. We compared
      negative life events experienced within 1 month, 1-3 months, 3-6 months, and 6-2
      months prior to attempted suicide for cases and prior to interview for controls.
      We used multivariate logistic regression to examine the association between NLEs
      and attempted suicide. RESULTS: Suicide attempters experienced more NLEs within
      the last year prior to suicide attempt than controls prior to interview (83.1%
      vs. 33.5%). There was a significant dose-response relationship between NLEs
      experienced within the last year and increased risk of attempted suicide. Timing
      of NLEs analysis showed that NLEs experienced in the last month and 6-12 months
      prior to suicide attempt were significantly associated with elevated risk of
      attempted suicide, even after adjusting for mental disorders and demographic
      factors. Of NLEs, quarrelling with spouse, quarrelling with other family members,
      conflicting with friends or neighbors, family financial difficulty, and serious
      illness were independently related to attempted suicide. CONCLUSION: NLEs are
      significantly associated with increased risk for attempted suicide in rural
      China. Stress management and intervention may be important to prevent suicidal
      behavior in rural China.

PMID- 25611855
TI  - Novel exons and splice variants in the human antibody heavy chain identified by
      single cell and single molecule sequencing.
AB  - Antibody heavy chains contain a variable and a constant region. The constant
      region of the antibody heavy chain is encoded by multiple groups of exons which
      define the isotype and therefore many functional characteristics of the antibody.
      We performed both single B cell RNAseq and long read single molecule sequencing
      of antibody heavy chain transcripts and were able to identify novel exons for
      IGHA1 and IGHA2 as well as novel isoforms for IGHM antibody heavy chain. 

PMID- 25611856
TI  - Vibrationally resolved photoelectron spectroscopy of electronic excited states of
      DNA bases: application to the a state of thymine cation.
AB  - For fully understanding the light-molecule interaction dynamics at short time
      scales, recent theoretical and experimental studies proved the importance of
      accurate characterizations not only of the ground (D0) but also of the electronic
      excited states (e.g., D1) of molecules. While ground state investigations are
      currently straightforward, those of electronic excited states are not. Here, we
      characterized the A electronic state of ionic thymine (T(+)) DNA base using
      explicitly correlated coupled cluster ab initio methods and state-of-the-art
      synchrotron-based electron/ion coincidence techniques. The experimental spectrum
      is composed of rich and long vibrational progressions corresponding to the
      population of the low frequency modes of T(+)(A). This work challenges previous
      numerous works carried out on DNA bases using common synchrotron and VUV-based
      photoelectron spectroscopies. We provide hence a powerful theoretical and
      experimental framework to study the electronic structure of ionized DNA bases
      that could be generalized to other medium-sized biologically relevant systems. 

PMID- 25611857
TI  - Influence of age at revision cochlear implantation on speech perception outcomes.
AB  - IMPORTANCE: This study reviewed whether advanced age should be a consideration
      when revision cochlear implantation is warranted. OBJECTIVE: To examine whether
      age at revision cochlear implantation is related to postrevision speech
      perception performance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      analysis was performed in an academic tertiary care center. Participants included
      14 younger adults (<65 years) and 15 older adults (>=65 years) who underwent
      revision cochlear implantation. INTERVENTION: Revision cochlear implantation.
      MAIN OUTCOMES AND MEASURES: Speech perception performance, as measured with
      consonant-nucleus-consonant [CNC] words in quiet, at the best prerevision
      interval as well as the 3- and 6-month postrevision intervals were compared
      between the 2 cohorts. The CNC word test consists of 10 lists of 50 phonemically
      balanced monosyllabic words, scored with a range of 0% to 100% correct. RESULTS:
      Both cohorts experienced a restoration in speech perception scores after revision
      cochlear implantation compared with their best performance before the revision
      (mean [SD] CNC word test scores for the younger cohort: 43.9% [25.6%] before
      revision and 47.7% [21.3%] at 3 months and 47.6% [19.8%] at 6 months after
      revision; for the older cohort: 36.3% [19.1%] before revision and 35.3% [17.2%]
      at 3 months and 39.9% [16.3%] at 6 months after revision; F2,54= 0.93; P = .40).
      There was no interaction between age at revision surgery and speech perception
      performance at each assessment interval (F2,54= 0.51; P = .60). CONCLUSIONS AND
      RELEVANCE: In this study, age at revision cochlear implantation was not related
      to postrevision speech perception performance. Advanced age should not be
      considered a contraindication to revision cochlear implantation.

PMID- 25611859
TI  - Tetrahydroindeno[1',2':4,5]pyrrolo[1,2-a]imidazol-5(1H)-ones as novel
      neonicotinoid insecticides: reaction selectivity and substituent effects on the
      activity level.
AB  - Tetraheterocyclic tetrahydroindeno[1',2':4,5]pyrrolo[1,2-a]imidazol-5(1H)-one
      derivatives as novel neonicotinoid candidates were designed and prepared by
      selective etherification, chlorination and esterification of ninhydrin
      heterocyclic ketene aminals adducts. Some of the designed compounds showed
      excellent insecticidal activity against cowpea aphids (Aphis craccivora), brown
      planthopper (Nilaparvata lugens), and armyworm (Mythimna separata). In
      particular, the activity against armyworm (Mythimna separata) improved a lot in
      contrast with that of imidacloprid and cycloxaprid. The research here provides a
      novel neonicotinoid chemotype for further development.

PMID- 25611860
TI  - Cardiac tamponade after transcatheter aortic valve replacement using a
      transaortic approach.
AB  - Transcatheter aortic valve replacement (TAVR) is considered an option for
      patients with severe aortic stenosis who are not surgical candidates. We describe
      the case of a patient who presented with cardiac tamponade shortly after
      uneventful TAVR by a direct aortic approach. The patient was brought to the
      operating room for exploration and repair. Although TAVR is less invasive than
      traditional open aortic valve replacement, TAVR nonetheless poses serious risk.
      This case highlights a potential complication of the less commonly used
      transaortic approach for TAVR and the importance of taking a multidisciplinary
      approach when identifying and managing all TAVR-associated complications. 

PMID- 25611861
TI  - Editorial comment: integrated care and teamwork: the rashomon effect in
      cardiovascular medicine.

PMID- 25611858
TI  - Tailoring the antibody response to aggregated Abeta using novel Alzheimer
      vaccines.
AB  - Recent evidence suggests Alzheimer-Disease (AD) to be driven by aggregated Abeta.
      Capitalizing on the mechanism of molecular mimicry and applying several selection
      layers, we screened peptide libraries for moieties inducing antibodies
      selectively reacting with Abeta-aggregates. The technology identified a pool of
      peptide candidates; two, AFFITOPES AD01 and AD02, were assessed as vaccination
      antigens and compared to Abeta1-6, the targeted epitope. When conjugated to
      Keyhole Limpet Hemocyanin (KLH) and adjuvanted with aluminum, all three peptides
      induced Abeta-targeting antibodies (Abs). In contrast to Abeta1-6, AD01- or AD02
      induced Abs were characterized by selectivity for aggregated forms of Abeta and
      absence of reactivity with related molecules such as Amyloid Precursor Protein
      (APP)/ secreted APP-alpha (sAPPa). Administration of AFFITOPE-vaccines to APP
      transgenic mice was found to reduce their cerebral amyloid burden, the associated
      neuropathological alterations and to improve their cognitive functions. Thus, the
      AFFITOME-technology delivers vaccines capable of inducing a distinct Ab response.
      Their features may be beneficial to AD-patients, a hypothesis currently tested
      within a phase-II-study. 

PMID- 25611863
TI  - Congenital tracheal stenosis: unanticipated and anticipated difficult airway
      management in a neonate.
AB  - We present the case of a neonate with congenital tracheal stenosis (1.4-mm
      diameter) who came to the operating room as both an unanticipated and anticipated
      case of difficult airway management. We discuss the airway management of newborn
      children with congenital tracheal stenosis, and rescue options for the difficult
      airway in very small children. 

PMID- 25611862
TI  - Propionic acidemia in a parturient presenting for induction of labor.
AB  - Propionic acidemia is a congenital disorder of metabolism where the enzyme
      propionyl-CoA carboxylase is nonfunctional, resulting in an accumulation of
      propionic acid in the blood. It is important to avoid excess protein intake and a
      catabolic state to prevent acidemia. Additionally, it may be wise to avoid
      anesthetic drugs metabolized by propionyl-CoA carboxylase because use of these
      drugs may lead to acidosis. We present a case of a parturient with propionic
      acidemia who presented for induction of labor. 

PMID- 25611864
TI  - Dysphagia, hoarseness, and a hypopharyngeal mass.
AB  - We describe a patient who developed a hypopharyngeal mass (in the setting of a
      cervical osteophyte) while taking clopidogrel and aspirin for coronary artery
      disease. He had a 2-month history of progressive dysphagia and hoarseness.
      Physical examination and computed tomography scan revealed a soft tissue
      retropharyngeal mass of unclear etiology yet with a stable airway. He was
      admitted to the intensive care unit for a 48-hour clopidogrel washout followed by
      surgery. A hematoma and cervical osteophyte were removed with scant bleeding.
      This case report emphasizes the need to consider the medication history of a
      patient when assessing the cause of an otherwise unexpected finding. 

PMID- 25611865
TI  - In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic
      computed tomography.
AB  - Using internal illumination with an optical fiber in the oral cavity, we
      demonstrate, for the first time, photoacoustic computed tomography (PACT) of the
      deep brain of rats in vivo. The experiment was performed on a full-ring-array
      PACT system, with the capability of providing high-speed cross-sectional imaging
      of the brain. Compared with external illumination through the cranial skull,
      internal illumination delivers more light to the base of the brain. Consequently,
      in vivo photoacoustic images clearly reveal deep brain structures such as the
      hypothalamus, brain stem, and cerebral medulla.

PMID- 25611866
TI  - Visualizing and quantifying difference in cytoplasmic and nuclear metabolism in
      the hepatobiliary system in vivo.
AB  - The liver is a major organ responsible for performing xenobiotic metabolism. In
      this process, xenobiotic is uptaken and processed in hepatocytes and subsequently
      excreted into the bile canaliculi. However, the intracellular heterogeneity in
      such metabolic processes is not known. We use the molecular probe 6
      carboxyfluorescein diacetate (6-CFDA) to investigate xenobiotic metabolism in
      hepatocytes with intravital multiphoton fluorescence microscopy. 6-CFDA is
      processed by intracellular esterase to fluorescent 6-CF, which can be imaged and
      quantified. We found that compared to the nucleus, cytoplasmic 6-CF fluorescence
      intensity reached a maximum earlier (cytoplasm: 11.3 +/- 4.4 min; nucleus: 14.7
      +/- 4.9 min) following 6-CFDA injection. We also found a slight difference in the
      rate of 6-CFDA metabolism as the rates of 6-CF decay at rates of 1.43 +/- 0.75
      and 1.27 +/- 0.72 photons/min for the cytoplasm and nucleus, respectively. These
      results indicate that molecular transport to the nucleus is additionally hindered
      and can affect drug transport there

PMID- 25611867
TI  - Texture analysis of collagen second-harmonic generation images based on local
      difference local binary pattern and wavelets differentiates human skin abnormal
      scars from normal scars.
AB  - Quantitative methods for noninvasive diagnosis of scars are a challenging issue
      in medicine. This work aims to implement a texture analysis method for
      quantitatively discriminating abnormal scars from normal scars based on second
      harmonic generation (SHG) images. A local difference local binary pattern (LD
      LBP) operator combined with a wavelet transform was explored to extract diagnosis
      features from scar SHG images that were related to the alteration in collagen
      morphology. Based on the quantitative parameters including the homogeneity,
      directional and coarse features in SHG images, the scar collagen SHG images were
      classified into normal or abnormal scars by a support vector machine classifier
      in a leave-one-out cross-validation procedure. Our experiments and data analyses
      demonstrated apparent differences between normal and abnormal scars in terms of
      their morphological structure of collagen. By comparing with gray level co
      occurrence matrix, wavelet transform, and combined basic local binary pattern and
      wavelet transform with respect to the accuracy and receiver operating
      characteristic analysis, the method proposed herein was demonstrated to achieve
      higher accuracy and more reliable classification of SHG images. This result
      indicated that the extracted texture features with the proposed method were
      effective in the classification of scars. It could provide assistance for
      physicians in the diagnostic process.

PMID- 25611868
TI  - Localizing fluorophore (centroid) inside a scattering medium by depth
      perturbation.
AB  - Fluorescence molecular tomography (FMT) imaging can be used to determine the
      location, size, and biodistribution of fluorophore biomarkers inside tissues. Yet
      when using FMT in the reflectance geometry it is challenging to accurately
      localize fluorophores. A depth perturbation method is proposed to determine the
      centroid of fluorophore inside a tissue-like medium. Through superposition of a
      known thin optical phantom onto the medium surface, the fluorophore depth is
      deliberately perturbed and signal localization is improved in a stable way. We
      hypothesize that the fluorophore centroid can be better localized through use of
      this fluorescent intensity variation resulting from the depth perturbation. This
      hypothesis was tested in tissue-like phantoms. The results show that a small-size
      fluorophore inclusion (1.2 mm(3)volume, depth up to 4.8 mm) can be localized by
      the method with an error of 0.2 to 0.3 mm. The method is also proven to be
      capable of handling multiple fluorescent inclusion conditions with the assistance
      of other strategies. Additionally, our further studies showed that the method's
      performance in the presence of background fluorophores indicated that the small
      inclusion could be located at a 1.8 (3.8) mm depth with accurate localization
      only when its concentration was not <10 (100) times the background level.

PMID- 25611870
TI  - Dual gold catalysis: a novel synthesis of bicyclic and tricyclic pyrroles from N
      propargyl ynamides.
AB  - Various N-propargyl ynamides were converted to bicylic and tricyclic pyrroles by
      the use of a cationic dual-activation gold catalyst. This reaction starts with
      the nucleophilic addition of a gold acetylide onto an ynamide triple bond at the
      beta-position of the nitrogen atom. Thus, gold vinylidene is formed, and then a
      second cyclization takes place. The formation of the gold vinylidene is indicated
      by the evidence that not only aryl ynamides but also alkyl ynamides undergo C-H
      activation in these reactions. 

PMID- 25611871
TI  - Depletion stabilization in nanoparticle-polymer suspensions: multi-length-scale
      analysis of microstructure.
AB  - We study the mechanism of depletion stabilization and the resultant
      microstructure of aqueous suspensions of nanosized silica and poly(vinyl alcohol)
      (PVA). Rheology, small-angle light scattering (SALS), and small-angle X-ray
      scattering (SAXS) techniques enable us to analyze the microstructure at broad
      length scale from single particle size to the size of a cluster of aggregated
      particles. As PVA concentration increases, the microstructure evolves from
      bridging flocculation, steric stabilization, depletion flocculation to depletion
      stabilization. To our surprise, when depletion stabilization occurs, the
      suspension shows the stabilization at the cluster length scale, while maintaining
      fractal aggregates at the particle length scale. This sharply contrasts
      previously reported studies on the depletion stabilization of microsized particle
      and polymer suspensions, which exhibits the stabilization at the particle length
      scale. On the basis of the evaluation of depletion interaction, we propose that
      the depletion energy barrier exists between clusters rather than particles due to
      the comparable size of silica particle and the radius gyration of PVA. 

PMID- 25611873
TI  - Editorial Comment: Possible Neonatal Herpes Simplex Virus (HSV) Acquired
      Postpartum from Maternal Oral HSV Reactivation after Neuraxial Morphine.

PMID- 25611872
TI  - Possible Neonatal Herpes Simplex Virus (HSV) Acquired Postpartum from Maternal
      Oral HSV Reactivation after Neuraxial Morphine.
AB  - In this report, we describe a case of a neonatal oral herpes simplex virus (HSV)
      infection possibly acquired from a mother who had oral HSV reactivation in
      association with neuraxial morphine. Neuraxial morphine is commonly administered
      for postpartum analgesia after cesarean delivery. While there is evidence that
      neuraxial morphine increases the risks of oral HSV reactivation in parturients,
      there has been no report of neonatal HSV infection directly acquired from a
      mother who had HSV recurrence from neuraxial morphine. 

PMID- 25611874
TI  - Spinal anesthesia for cesarean delivery in a woman with neuromyelitis optica.
AB  - Neuromyelitis optica (NMO), or Devic's disease, is an idiopathic severe
      demyelinating disease that preferentially affects the optic nerve and spinal
      cord. Neuraxial anesthesia in women with multiple sclerosis is widely accepted,
      but reports of the use of neuraxial anesthesia in patients with NMO are scarce.
      We report the case of a morbidly obese primigravida undergoing a planned cesarean
      delivery at 32 weeks' gestation due to an acute exacerbation of NMO, managed with
      spinal anesthesia. Other than increased intraoperative hyperalgesia requiring
      inhaled nitrous oxide/oxygen, the mother experienced no apparent anesthetic
      related complications. 

PMID- 25611875
TI  - Serotonin syndrome caused by administration of methylene blue to a patient
      receiving selective serotonin reuptake inhibitors.
AB  - A 31-year-old man who had surgery after a gunshot injury was recovering in the
      intensive care unit when a sudden deterioration in his condition occurred after
      enteral administration of methylene blue to detect a fistula. Serotonin syndrome
      was diagnosed based on hyperthermia, ocular clonus, and excessive diaphoresis. 

PMID- 25611876
TI  - Serotonin syndrome after cardiopulmonary bypass: a case demonstrating the
      interaction between methylene blue and selective serotonin reuptake inhibitors.
AB  - Methylene blue, a drug used to treat vasoplegia and methemoglobinemia, also
      inhibits monoamine oxidase-A. When given in combination with serotonergic
      medications, methylene blue can lead to serotonin excess syndrome. Given the
      widespread use of serotonergic medication to treat depression, anesthesia
      providers should be aware of this potentially lethal interaction. Patients
      undergoing cardiopulmonary bypass for cardiac surgery are a specific population
      at risk for postbypass vasoplegic shock. The use of methylene blue to treat
      vasoplegia in this group of patients should be weighed in light of their current
      medications and potential drug interactions. 

PMID- 25611877
TI  - Editorial comment: serotonin syndrome after cardiopulmonary bypass: a case
      demonstrating the interaction between methylene blue and selective serotonin
      reuptake inhibitors and serotonin syndrome caused by administration of methylene
      blue to a patient receiving selective serotonin reuptake inhibitors.

PMID- 25611878
TI  - Immunological mechanisms in allergic contact dermatitis.
AB  - PURPOSE OF REVIEW: Allergic contact dermatitis is a skin disease resulting from
      an adverse reaction of the immune system to low-molecular-weight organic
      chemicals or metal ions. This review summarizes recent findings that highlight
      new details of the complex orchestration of the cellular and molecular immune
      response to contact allergens. RECENT FINDINGS: Progress has been made in the
      characterization of the roles of natural killer T cells, natural killer cells,
      mast cells and neutrophils, as well as in the elucidation of signaling pathways
      triggered by contact allergens. Global technologies begin to reveal gene
      signatures for contact allergen identification and improved diagnostics. SUMMARY:
      Recent progress in contact allergy research has deepened our understanding of the
      molecular and cellular pathomechanisms, and opens new avenues towards improved
      diagnostics and treatments, as well as prevention and risk assessment strategies.

PMID- 25611879
TI  - Dark-adapted visual function with retinal structural changes in patients with
      Stargardt disease.

PMID- 25611880
TI  - Reply: To PMID 24280667.

PMID- 25611881
TI  - Biotic ligand model does not predict the bioavailability of rare Earth elements
      in the presence of organic ligands.
AB  - Due to their distinct physicochemical properties, rare earth elements (REEs) are
      critical to high-tech and clean-energy industries; however, their bioavailability
      is still largely unexplored. In this paper, the bioavailability of several REEs
      has been carefully examined for the freshwater alga, Chlamydomonas reinhardtii.
      In the presence of organic ligands (L), the biouptake of REEs was much higher
      than that predicted by the biotic ligand model (BLM). Enhancement of the
      biouptake flux was observed for six ligands (metal = thulium) and six REEs
      (ligand = citric acid), indicating that this could be a common feature for these
      metals. In order to explore the mechanism for the enhanced uptake, Tm
      internalization was carefully evaluated. The Tm internalization flux (Jint)
      followed first-order (Michaelis-Menten) kinetics with a calculated maximum
      internalization flux (Jmax) of (1.1 +/- 0.08) * 10(-14) mol . cm(-2) . s(-1) and
      an affinity constant for the reaction of the metal with the transport sites (KTm
      R) of 10(7.1) M(-1). In the presence of citric acid, malic acid, or NTA, the Jint
      for Tm was more than 1 order of magnitude higher than that predicted by the BLM
      when algae were exposed to a constant 10(-9) M Tm(3+). The bioavailability of the
      metal complexes could not be explained by a piggyback internalization (through an
      anion channel) or the contribution of labile complexes. The enhanced biouptake
      was attributed to the formation of a ternary Tm complex {L-Tm-R} at the metal
      transport site. In the natural environment where organic ligands are ubiquitous,
      classic models are unlikely to predict the bioavailability of REEs to aquatic
      organisms.

PMID- 25611882
TI  - Controlling self-assembly of reduced graphene oxide at the air-water interface:
      quantitative evidence for long-range attractive and many-body interactions.
AB  - Industrial-scale applications of two-dimensional materials are currently limited
      due to lack of a cost-effective and controlled synthesis method for large-area
      monolayer films. Self-assembly at fluid interfaces is one promising method. Here,
      we present a quantitative analysis of the forces governing reduced graphene oxide
      (rGO) assembly at the air-water interface using two unique approaches: area-based
      radial distribution functions and a theoretical Derjaguin-Landau-Verwey-Overbeek
      (DLVO) interaction potential for disks interacting edge-to-edge. rGO aggregates
      at the air-water interface when the subphase ionic strength results in a Debye
      screening length equal to the rGO thickness (~1 mM NaCl), which is consistent
      with the DLVO interaction potential. At lower ionic strengths, area-based radial
      distribution functions indicate that rGO-rGO interactions at the air-water
      interface are dominated by long-range (tens of microns) attractive and many-body
      repulsive forces. The attractive forces are electrostatic in nature; that is, the
      force is weakened by minor increases in ionic strength. A quantitative
      understanding of rGO-rGO interactions at the air-water interface may allow for
      rational synthesis of large-area atomically thin films that have potential for
      planar electronics and membranes. 

PMID- 25611883
TI  - Clinical course of chronic hepatitis B (CHB) presented with normal ALT in Asian
      American patients.
AB  - The clinical course for chronic hepatitis B (CHB) patients with normal ALT and
      with or without minimal histologic activity remains unclear. We assessed
      frequency, amplitude, disease activities, and associated factors of ALT and/or
      AST flares in this subpopulation. Forty-seven consecutive treatment naive Asian
      patients with CHB were enrolled from two liver clinics between December 2003 and
      January 2013, who had normal baseline ALT by routine clinical biochemical testing
      performed 6 weeks before or after the liver biopsy. We defined a flare as
      elevation of ALT/AST above the upper limit of normal of ALT/AST. The mean follow
      up was 37.6 (CI = 12, 88) months, and the mean age at entry into the study was
      43.3 (CI = 19, 65); 22/47 (46.8%) were males; 15/45 (33.3%), HBeAg+; 68.1% had
      stage 0-1 fibrosis; 63.8% had grade 0-1 inflammation. During follow-up, 13/47
      (27.7%) cases developed ALT flare at least once in a mean of 13.5 (CI = 2, 43)
      months after liver biopsy; ALT flare was not associated with baseline ALT level,
      fibrosis stage, inflammation grade, hepatitis B virus (HBV) DNA load, HBeAg
      status, HBV genotype, HBV precore and basal core promoter mutations. 11/13
      (84/6%) of ALT flares resolved during follow-up. 13/13 (100%) of ALT flares met
      AASLD treatment criteria, but only 6/13 (46.2%) were on HBV treatment. Serum ALT
      and/or AST flares occur frequently in CHB carriers who initially presented with
      normal ALT during pretreatment period. Thus, regular follow-up is warranted
      despite status of ALT/AST. No clinical factors were found to be associated with
      ALT flares.

PMID- 25611884
TI  - Metal-free, efficient hydrazination of imidazo[1,2-a]pyridine with diethyl
      azodicarboxylate in neutral media.
AB  - The first example of metal-free regioselective hydrazination of imidazo[1,2
      a]pyridine with diethyl azodicarboxylate is accomplished. This procedure is
      chemically appealing due to the high degree of functional group tolerance and
      efficiency in expanding the molecular diversity. 

PMID- 25611886
TI  - High prevalence of hepatitis B nonimmunity in vaccinated pediatric liver
      transplant recipients.
AB  - Durable protection from hepatitis B virus (HBV) and other vaccine-preventable
      diseases assumes great importance due to improved long-term patient and graft
      survival rates in pediatric liver transplantation. Vaccine immunogenicity data in
      transplanted children is limited. This was a cross-sectional, single-center,
      point-prevalence study evaluating HBV immunity in 160 pediatric liver transplant
      recipients. Patients with hepatitis B surface antibody levels <10 IU/L were
      considered nonimmune. Predictor variables for nonimmunity identified in
      univariate analyses were later analyzed within a logistic regression model. All
      subjects received the full HBV vaccination series prior to transplant. The
      majority (67%) of previously immunized pediatric liver transplant patients were
      nonimmune. Older children (p < 0.001) and children who were further out from
      transplant (p < 0.001) were more likely to be nonimmune in univariate analyses,
      but only time from transplant was a significant predictor of nonimmunity in a
      logistic regression model (odds ratio 1.3, p < 0.001 at 1 year). The mean time
      since transplant was 5.6 years +/- 4.6. Markers of nutrition, immunosuppression,
      white blood cell parameters and type/severity of disease did not correlate with
      HBV immunity. Information on the anamnestic response to boosting or revaccination
      is needed to adequately address this vulnerable group.

PMID- 25611887
TI  - Carbon-protected bimetallic carbide nanoparticles for a highly efficient alkaline
      hydrogen evolution reaction.
AB  - The hydrogen evolution reaction (HER) is one of the two important half reactions
      in current water-alkali and chlor-alkali electrolyzers. To make this reaction
      energy-efficient, development of highly active and durable catalytic materials in
      an alkaline environment is required. Herein we report the synthesis of carbon
      coated cobalt-tungsten carbide nanoparticles that have proven to be efficient
      noble metal-free electrocatalysts for alkaline HER. The catalyst affords a
      current density of 10 mA cm(-2) at a low overpotential of 73 mV, which is close
      to that (33 mV) required by Pt/C to obtain the same current density. In addition,
      this catalyst operates stably at large current densities (>30 mA cm(-1)) for as
      long as 18 h, and gives nearly 100% Faradaic yield during alkaline HER. The
      excellent catalytic performance (activity and stability) of this nanocomposite
      material is attributed to the cooperative effect between nanosized bimetallic
      carbide and the carbon protection layer outside the metal carbide. The results
      presented herein offer the exciting possibility of using carbon-armoured metal
      carbides for an efficient alkaline HER, although pristine metal carbides are not,
      generally, chemically stable enough under such strong alkaline conditions. 

PMID- 25611885
TI  - Treatment-related biomarkers in pulmonary hypertension.
AB  - Significant advances in the treatment of pulmonary arterial hypertension (PAH)
      over the last two decades have led to the introduction of multiple classes of
      oral therapy, but the disease remains devastating for many patients. Disease
      progression, in spite of oral monotherapy, is a major problem, and alternative
      therapy, such as infusion of prostacyclins, is cumbersome and carries
      considerable potential morbidity. Use of combination oral therapy, including
      drugs from both the endothelin receptor antagonist and phosphodiesterase-5
      inhibitor classes, has increased, and there is some evidence to support this
      approach. Given the multiple options now available in pulmonary hypertension (PH)
      therapy, biomarkers to guide treatment decisions could be helpful. Here, we
      review the evidence for and against the clinical use of molecular biomarkers
      relevant to PH pathogenesis, emphasizing assayable markers that may also inform
      more rational selection of agents that influence pathways targeted by treatment.
      We emphasize the interactive nature of changes in mediators and messengers, such
      as endothelin-1, prostacyclin, brain natriuretic peptide (which has demonstrated
      biomarker utility), nitric oxide derivatives, and cyclic guanosine monophosphate,
      which play important roles in processes central to progression of PAH, such as
      vascular remodeling, vasoconstriction, and maladaptive right ventricular changes,
      and are relevant to its therapy. Accordingly, we propose that the identification
      and use of a molecular biomarker panel that assays these molecules in parallel
      and serially might, if validated, better inform unique patient phenotypes,
      prognosis, and the rational selection and titration of combination oral and other
      therapy in individual patients with PH/PAH. 

PMID- 25611888
TI  - A porous ZnGaNO photoanode for efficient water oxidation modified by a Co-based
      electrocatalyst.
AB  - Porous ZnGaNO microrods were synthesized by a single crystal internal
      decomposition route, and exhibited high performance in photoelectrochemical water
      splitting due to the high specific area and short charge transfer distance of the
      microstructure. 

PMID- 25611889
TI  - Elucidating the real-time Ag nanoparticle growth on alpha-Ag2WO4 during electron
      beam irradiation: experimental evidence and theoretical insights.
AB  - Why and how Ag is formed when electron beam irradiation takes place on alpha
      Ag2WO4 in a vacuum transmission electron microscopy chamber? To find an answer,
      the atomic-scale mechanisms underlying the formation and growth of Ag on alpha
      Ag2WO4 have been investigated by detailed in situ transmission electron
      microscopy (TEM) and field emission scanning electron microscopy (FE-SEM)
      studies, density functional theory based calculations and ab initio molecular
      dynamics simulations. The growth process at different times, chemical
      composition, size distribution and element distribution were analyzed in depth at
      the nanoscale level using FE-SEM, operated at different voltages (5, 10, 15, and
      20 kV), and TEM with energy dispersive spectroscopy (EDS) characterization. The
      size of Ag nanoparticles covers a wide range of values. Most of the Ag particles
      are in the 20-40 nm range. The nucleation and formation of Ag on alpha-Ag2WO4 is
      a result of structural and electronic changes in the AgOx (x = 2,4, 6, and 7)
      clusters used as constituent building blocks of this material, consistent with
      metallic Ag formation. First principle calculations point out that Ag-3 and Ag-4
      fold coordinated centers, located in the sub-surface of the (100) surface, are
      the most energetically favorable to undergo the diffusion process to form
      metallic Ag. Ab initio molecular dynamics simulations and the nudged elastic band
      (NEB) method were used to investigate the minimum energy pathways of these Ag
      atoms from positions in the first slab layer to outward sites on the (100)
      surface of alpha-Ag2WO4. The results point out that the injection of electrons
      decreases the activation barrier for this diffusion step and this unusual
      behavior results from the presence of a lower energy barrier process. 

PMID- 25611890
TI  - Gross efficiency during flat and uphill cycling in field conditions.
AB  - PURPOSE: While a number of studies have investigated gross efficiency (GE) in
      laboratory conditions, few studies have analyzed it in field conditions.
      Therefore, the aim of this study was to analyze the effect of gradient and
      cadence on GE in field conditions. METHODS: Thirteen trained cyclists (mean +/-
      SD age 23.3 +/- 4.1 y, stature 177.0 +/- 5.5 cm, body mass 69.0 +/- 7.2 kg,
      maximal oxygen uptake [VO2max] 68.4 +/- 5.1 mL . min-1 .kg-1) completed an
      incremental graded exercise test to determine ventilatory threshold (VT) and 4
      field trials of 6 min duration at 90% of VT on flat (1.1%) and uphill terrain
      (5.1%) with 2 different cadences (60 and 90 rpm). VO2 was measured with a
      portable gas analyzer and power output was controlled with a mobile power crank
      that was mounted on a 26-in mountain bike. RESULTS: GE was significantly affected
      by cadence (20.6% +/- 1.7% vs 18.1% +/- 1.3% at 60 and 90 rpm, respectively; P <
      .001) and terrain (20.0% +/- 1.5% vs 18.7% +/- 1.7% at flat and uphill cycling,
      respectively; P = .029). The end-exercise VO2 was 2536 +/- 352 and 2594 +/- 329
      mL/min for flat and uphill cycling, respectively (P = .489). There was a
      significant difference in end-exercise VO2 between 60 (2352 +/- 193 mL/min) and
      90 rpm (2778 +/- 431 mL/min) (P < .001). CONCLUSION: These findings support
      previous laboratory-based studies demonstrating reductions in GE with increasing
      cadence and gradient that might be attributed to changes in muscle-activity
      pattern.

PMID- 25611891
TI  - Mortality of intentional and unintentional pesticide poisonings in Germany from
      1980 to 2010.
AB  - Pesticide poisoning is a major public health issue especially in low-income
      countries. WHO figures show about 3 million pesticide poisonings occurring
      worldwide annually. A recent systematic review estimated that 360,000 fatalities
      result from self-poisoning with pesticides, accounting for approximately 30 per
      cent of all suicides worldwide. We analyzed the German cause-of-death registry
      with respect to pesticide-specific ICD codes. We present crude and age
      standardized mortality rates plus the percentage of all suicides that are
      intentional pesticide poisonings. From 1980 to 2010 the number of fatal pesticide
      poisoning in Germany dropped from 506 to 39. The crude mortality rate decreased
      from 6.5 per 1 million inhabitants in 1980 to 0.5 in 2010. Reduced availability
      of toxic pesticides in Germany played the biggest role in the decline of fatal
      pesticide poisoning. We worry that declines in pesticide poisonings in
      industrialized countries are not matched in developing countries.

PMID- 25611892
TI  - Translating active living research into policy and practice: one important
      pathway to chronic disease prevention.
AB  - Global concerns about rising levels of chronic disease make timely translation of
      research into policy and practice a priority. There is a need to tackle common
      risk factors: tobacco use, unhealthy diets, physical inactivity, and harmful
      alcohol use. Using evidence to inform policy and practice is challenging, often
      hampered by a poor fit between academic research and the needs of policymakers
      and practitioners--notably for active living researchers whose objective is to
      increase population physical activity by changing the ways cities are designed
      and built. We propose 10 strategies that may facilitate translation of research
      into health-enhancing urban planning policy. Strategies include interdisciplinary
      research teams of policymakers and practitioners; undertaking explicitly policy
      relevant research; adopting appropriate study designs and methodologies
      (evaluation of policy initiatives as 'natural experiments'); and adopting
      dissemination strategies that include knowledge brokers, advocates, and
      lobbyists. Conducting more policy-relevant research will require training for
      researchers as well as different rewards in academia.

PMID- 25611893
TI  - Origins, bottlenecks, and present-day diversity: patterns of morphospace
      occupation in marine bivalves.
AB  - It has long been known that species should not be distributed randomly in
      morphospace (a multidimensional trait space), even under simple models of
      evolution. However, recent studies suggest that position in morphospace can
      affect aspects of evolution such as the durations of clades and the species
      richness of their constituent taxa. Here we investigate the dynamics of
      morphospace occupancy in living and fossil marine bivalves using shell size and
      aspect ratio, two functionally important traits. Multiple lines of evidence
      indicate that the center of a family's morphospace today represents a location
      where taxonomic diversity is maximized, apparently owing to lower extinction
      rates. Within individual bivalve families, species with narrow geographic ranges
      are distributed throughout the morphospace but widespread species, which are
      generally expected to be extinction resistant, tend to be concentrated near the
      center. The morphospace centers of most species-rich families today (defined as
      the median value for all species in the family) tend to be close to the positions
      of the family founders, further suggesting an association between position in
      morphospace and net diversification rates. However, trajectories of individual
      subclades (genera) are inconsistent with the center of morphospace being an
      evolutionary attractor. 

PMID- 25611895
TI  - Concerns about robotic extraperitoneal para-aortic lymphadenectomy as isolated
      procedure: is it worth it?

PMID- 25611897
TI  - Increased Notch1 expression is associated with poor overall survival in patients
      with ovarian cancer.
AB  - OBJECTIVE: Despite improvements in surgery and chemotherapy, ovarian cancer
      remains a deadly disease in need of improved therapies. We have previously shown
      that Notch1 intracellular domain (NICD) is highly expressed in ovarian cancer. We
      have also shown that NICD inhibition can lead to growth arrest in ovarian cancer
      cells. The objective of the current study was to delineate whether NICD
      expression correlates with prognosis of women with ovarian cancer. METHODS: After
      the institutional review board approval, patients with a diagnosis of primary
      ovarian cancer between the years 2001 and 2007 who underwent surgery at our
      institution were identified. Paraffin blocks from the primary ovarian tumor were
      analyzed, and core samples were obtained to build a tissue microarray.
      Cytoplasmic NICD expression was assessed by quantitative immunofluorescent
      morphometry using the automated quantitative analysis system. These results were
      correlated with clinical and pathology data retrieved from the patient records.
      RESULTS: We identified 328 patients with primary ovarian cancer during this
      period. Seventeen percent of patients had stage I, 11% had stage II, 59% had
      stage III, and 13% had stage IV disease. Most patients (70%) had papillary serous
      histology, and most (86%) underwent optimal debulking to less than 1 cm of
      residual disease. High NICD expression was found to correlate strongly with low
      overall survival (P = 0.001). This effect remained in multivariate analysis (P =
      0.023). CONCLUSIONS: High expression of NICD in the primary tumor of women with
      ovarian cancer is an independently poor prognostic factor for overall survival.
      Further research into the therapeutic inhibition of the Notch1 pathway is
      warranted.

PMID- 25611896
TI  - Risk factors and indications for 30-day readmission after primary surgery for
      epithelial ovarian cancer.
AB  - BACKGROUND: To identify patients at risk for postoperative morbidities, we
      evaluated indications and factors associated with 30-day readmission after
      epithelial ovarian cancer surgery. METHODS: Patients undergoing primary surgery
      for epithelial ovarian cancer between January 2, 2003, and December 29, 2008,
      were evaluated. Univariable and multivariable logistic regression models were fit
      to identify factors associated with 30-day readmission. A parsimonious
      multivariable model was identified using backward and stepwise variable
      selection. RESULTS: In total, 324 (60.2%) patients were stage III and 91 (16.9%)
      were stage IV. Of all 538 eligible patients, 104 (19.3%) were readmitted within
      30 days. Cytoreduction to no residual disease was achieved in 300 (55.8%)
      patients, and 167 (31.0%) had measurable disease (<=1 cm residual disease). The
      most common indications for readmission were surgical site infection (SSI;
      21.2%), pleural effusion/ascites management (14.4%), and thromboembolic events
      (12.5%). Multivariate analysis identified American Society of Anesthesiologists
      score of 3 or higher (odds ratio, 1.85; 95% confidence interval, 1.18-2.89; P =
      0.007), ascites [1.76 (1.11-2.81); P = 0.02], and postoperative complications
      during initial admission [grade 3-5 vs none, 2.47 (1.19-5.16); grade 1 vs none,
      2.19 (0.98-4.85); grade 2 vs none, 1.28 (0.74-2.21); P = 0.048] to be
      independently associated with 30-day readmission (c-index = 0.625). Chronic
      obstructive pulmonary disease was the sole predictor of readmission for SSI (odds
      ratio, 3.92; 95% confidence interval, 1.07-4.33; P = 0.04). CONCLUSIONS:
      Clinically significant risk factors for 30-day readmission include American
      Society of Anesthesiologists score of 3 or higher, ascites and postoperative
      complications at initial admission. The SSI and pleural effusions/ascites are
      common indications for readmission. Systems can be developed to predict patients
      needing outpatient management, improve care, and reduce costs.

PMID- 25611898
TI  - A prospective, comparative study on robotic versus open-surgery hysterectomy and
      pelvic lymphadenectomy for endometrial carcinoma.
AB  - OBJECTIVES: The aim of this study was to compare surgical outcome, patient
      recovery, and costs between robot-assisted laparoscopy and laparotomy in women
      undergoing hysterectomy, bilateral salpingo-oophorectomy (BSOE), and pelvic
      lymphadenectomy for endometrial carcinoma. METHODS: Women undergoing
      hysterectomy, BSOE, and pelvic lymphadenectomy for endometrial carcinoma,
      according to regional guidelines, were prospectively, concurrently, and
      consecutively included from September 2010 to December 2012. Surgical outcomes
      such as operative time, estimated blood loss (EBL), number of lymph nodes
      retrieved, and complications were analyzed together with hospital stay, days
      until normal active daily living was retrieved, patient satisfaction with the
      length of the hospital stay, and cost per patient. Robot-assisted laparoscopy was
      performed on all cases at the Sahlgrenska University Hospital, and laparotomy was
      performed on all cases at 3 regional hospitals. RESULTS: Forty women underwent
      robot-assisted laparoscopy, and 48 underwent laparotomy. There were no
      differences in age, body mass index, histology, or retrieved lymph nodes.
      Operative time was significantly shorter in the robot-assisted laparoscopy group
      (P < 0.0001). The EBL was lower and hospital stay was shorter in the robot
      assisted laparoscopy group (P < 0.0001). There was no statistical difference in
      complications between the groups, and both groups found hospital stay duration
      satisfactory. In the robot-assisted laparoscopy group, active daily living was
      normal within 5 days postoperatively, compared with 14 days in the laparotomy
      group (P < 0.0001). Calculated costs per treated patient did not differ
      statistically between the groups. CONCLUSIONS: Compared with laparotomy and robot
      assisted laparoscopic hysterectomy, BSOE pelvic lymphadenectomy for endometrial
      carcinoma was associated with significantly shorter operative time, hospital
      stay, and lower EBL. Patients recovered more quickly after robot-assisted
      laparoscopy, with equal costs number of retrieved lymph nodes, compared with
      laparotomy.

PMID- 25611899
TI  - Carboplatin and nonpegylated liposomal doxorubicin in primary advanced or
      recurrent endometrial cancer: a phase 2 trial conducted by AGO Austria.
AB  - OBJECTIVE: Recurrent/advanced endometrial carcinoma carries a poor prognosis.
      Chemotherapy usually consists of cisplatin/doxorubicin and paclitaxel or the
      doublet of carboplatin and paclitaxel.We report on final results of the Austrian
      phase 2 AGO trial of nonpegylated doxorubicin citrate and carboplatin in 39
      patients with primary advanced or relapsed endometrial cancer. The main primary
      end point is response rate, and the main secondary end point is feasibility.
      METHODS: Thirty-nine patients received 60 mg/m nonpegylated doxorubicin citrate
      and carboplatin (area under the curve, 5) every 3 weeks for 6 to 9 cycles or
      until progression. Best response during therapy, progression-free survival, and
      the toxicity profile were recorded. RESULTS: Thirteen patients (33%) had primary
      advanced disease, and 26 patients (67%) had recurrent disease. Seventy-five
      percent of the tumors were adenocarcinomas, 15% were serous carcinomas, and 5%
      were clear cell and mixed mullerian carcinomas. We observed 1 complete response
      (3%) and 16 partial responses (41%) in the intention-to-treat population. The
      median progression-free survival was 7.2 months, and the median overall survival
      was 14.7 months. Overall, 177 cycles were administered; the mean number of cycles
      per patient was 4.5. Ten percent of patients received 9 cycles of chemotherapy,
      and 44% of patients received 6 cycles of chemotherapy. Grade 3/4 neutropenia
      occurred in 17%, grade 3/4 anemia in 5%, and grade 3/4 thrombopenia in 12% of the
      cycles. In 6% of the cycles, febrile neutropenia was noticed. Grade 3/4 nausea
      was seen in 5% of cycles. One patient (3%) experienced cardiac toxicity and had a
      reduction in the left ventricular ejection fraction to below 50%. CONCLUSIONS:
      The reported combination demonstrates considerable activity and should be
      evaluated further.

PMID- 25611900
TI  - Clinical outcomes of uterine carcinosarcoma: results of 94 patients.
AB  - OBJECTIVE: We aimed to determine the clinicopathologic features and identify
      prognostic factors of patients with uterine carcinosarcoma. MATERIALS AND
      METHODS: A total of 94 patients with uterine carcinosarcoma who were diagnosed
      between January 1993 and October 2013 were included. Staging surgery consisted of
      total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para
      aortic lymphadenectomy, peritoneal cytology, and omentectomy. Staging is
      undertaken according to the 2009 International Federation of Gynecology and
      Obstetrics staging system. Kaplan-Meier survival analysis was used to determine
      the effects of variables on disease-free survival (DFS) and overall survival
      (OS). RESULTS: Seventy-nine patients underwent staging surgery and none of them
      had residual tumor after surgery. Three-year DFS and 3-year OS were 42.7% and
      59.2%, respectively. In the univariate analysis, stage, presence of para-aortic
      metastatic lymph nodes, uterine serosal spread, positive peritoneal cytology, and
      extrapelvic metastases were associated with 3-year DFS and stage, presence of
      para-aortic metastatic lymph nodes, uterine serosal spread, positive peritoneal
      cytology, adnexal involvement, and extrapelvic metastases were associated with 3
      year OS. Seventy-four patients received adjuvant therapy. Adjuvant therapy did
      not reduce recurrence or improve survival. Any of the chemotherapy regimens was
      not superior to the others. In the multivariate analysis, only age was an
      independent prognostic factor for 3-year DFS and no parameter was statistically
      significant for 3-year OS. CONCLUSIONS: Age was an independent prognostic factor
      for 3-year DFS. Older age was associated with poor survival. Extrauterine spread
      was associated with survival. The aims of surgery should be both staging and
      providing tumoral debulking. Prospective randomized trials are needed to better
      define the necessity and modality of the administered adjuvant therapy.

PMID- 25611901
TI  - Endoscopic groin lymphadenectomy with a thigh approach to gynecologic
      malignancies: a retrospective study with 5-year experience.
AB  - OBJECTIVES: The objective of this study was to report a safe and feasible
      technique with endoscopic groin lymphadenectomy (EGL) through thigh approach in
      the treatment of different gynecologic malignancies. STUDY DESIGN: Consecutive
      gynecological malignant patients proceeded to groin lymphadenectomy were treated
      by this technique over a 5-year period (2005 to 2010). Data regarding the
      surgical perioperative complications were recorded. RESULTS: Eleven patients with
      21 EGL were performed. Procedures included bilateral groin lymphadenectomy (n =
      10) and left groin lymphadenectomy (n = 1). The median patient age and body mass
      index were 61 years and 25.2, respectively. The median operational time, which
      includes the dissection of both groins and the other procedures, was 210 minutes.
      The median blood loss was 200 mL. The median number of retrieved lymph nodes was
      13 (range, 8-26), and all of these are histologically negative. No intraoperative
      complications occurred. One patient was noted in cutaneous cellulitis on the
      right side of the patient with clinical resolution 15 days after surgery. There
      were no perioperative mortalities. All the cutaneous scars were healed without
      wound breakdown. There were no perioperative mortalities. At the latest follow
      up, all patients were completely satisfied with the cosmetic results.
      CONCLUSIONS: In this study, we first report EGL with a thigh approach in
      gynecologic malignancies; it is a safe and feasible technique, for groin nodal
      dissection, with low risks of morbidity of the skin and legs. A larger
      prospective study with long-term and survival analyses is warranted.

PMID- 25611902
TI  - Decreased anthocyanidin reductase expression strongly decreases silver birch
      (Betula pendula) growth and alters accumulation of phenolics.
AB  - Phenolics, formed via a complex phenylpropanoid pathway, are important defensive
      agents in plants and are strongly affected by nitrogen (N) fertilization.
      Proanthocyanidins (PAs) are one possible endpoint of the phenylpropanoid pathway,
      and anthocyanidin reductase (ANR) represents a key enzyme in PA biosynthesis. In
      this study, the expression of silver birch (Betula pendula) anthocyanidin
      reductase BpANR was inhibited using the RNA interference (RNAi) method, in three
      consequent BpANR RNAi (ANRi birches) lines. The growth, the metabolites of the
      phenylpropanoid pathway, and the number of resin glands of the ANRi birches were
      studied when grown at two N levels. ANRi birches showed decreased growth and
      reduction in PA content, while the accumulation of total phenolics in both stems
      and leaves increased. Moreover, ANRi birches produced more resin glands than did
      wild-type (WT) birches. The response of ANRi birches to N depletion varied
      compared with that of WT birches, and in particular, the concentrations of some
      phenolics in stems increased in WT birches and decreased in ANRi birches. Because
      the inhibition of PAs biosynthesis via ANR seriously affected birch growth and
      resulted in accumulation of the precursors, the native level of PAs in plant
      tissues is assumed to be the prerequisite for normal plant growth. This draws
      attention to the real plant developmental importance of PAs in plant tissues. 

PMID- 25611903
TI  - X monosomy in a virilized female cat.
AB  - An infertile Siamese female cat was subjected for clinical, histological,
      cytogenetic and molecular studies due to ambiguous external genitalia (vulva,
      vagina, rudimentary penis and scrotum-like structure) and masculine behaviour. An
      elevated oestrogen activity and a detectable level of testosterone were found.
      The cat underwent laparotomy. The gonads and the uterus were removed and
      subjected for histological studies, which showed ovaries with corpora lutea and a
      some primordial follicles. Chromosome studies of lymphocyte and fibroblast
      cultures, with the use of Giemsa staining, G-banding and whole X chromosome
      painting by fluorescence in situ hybridization, revealed pure X monosomy.
      Molecular analysis showed the absence of the SRY gene. Our study revealed for the
      first time that X monosomy in cats may be associated with virilization, in spite
      of the lack of the SRY gene. 

PMID- 25611904
TI  - Structural investigation of thermo-responsive poly(2-isopropyl-2-oxazoline)
      hydrogel across the volume phase transition.
AB  - The deswelling and swelling behaviors of poly(2-isopropyl-2-oxazoline)-based
      hydrogel synthesized by a one-pot microwave-assisted solvent-free reaction were
      investigated. A distinct hydrophobic collapse of the hydrogel compared with the
      corresponding aqueous solution was observed by FT-IR spectroscopy combined with
      two-dimensional correlation spectroscopy (2DCOS) and perturbation-correlation
      moving-window (PCMW) analyses. The volume phase transition (VPT) temperature of
      35  degrees C during heating and the transition temperature range of 41-30 
      degrees C during cooling were determined, indicating different dynamic transition
      mechanisms during heating and cooling. Water expulsion starting from the benzene
      ring-centered hydrophobic spots to the surroundings was revealed during
      deswelling. However, during swelling, although the rebuilding of cross-linking
      hydrogen bond bridges provided a channel-like microstructure to reswell the
      hydrogel gradually, a slow, unusual recovery of the amide hydrogen bonds to water
      molecules was observed. 

PMID- 25611905
TI  - Attacking generalism: using numbers when your argument is weak.

PMID- 25611907
TI  - President's message. Rural generalism.

PMID- 25611909
TI  - Management of acute exacerbation of COPD in rural Alberta emergency departments.
AB  - INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (COPD)
      is a common presentation to emergency departments (EDs); however, limited
      information exists about the management of this condition in nonurban locations.
      We sought to examine the diagnostic and treatment approaches for acute
      exacerbation of COPD in 3 rural EDs, and to determine levels of adherence to
      recommendations from the Canadian Thoracic Society (CTS) clinical practice
      guideline. METHODS: We conducted retrospective chart reviews to explore the
      management of patients who presented to 3 rural EDs for acute exacerbation of
      COPD in 2011. Data are reported as medians and interquartile ranges (IQRs) and
      proportions. RESULTS: Over a 1-year period, 192 patients presented a total of 266
      times with acute exacerbation of COPD. The median age was 68 (IQR 58-77) years,
      and 54.9% of the patients were women. Diagnostic testing included chest
      radiography in 65.0%, blood tests in 45.1%, electrocardiography in 33.5%, and
      arterial blood gas tests in 6.4%; only a few patients received pulmonary function
      testing. In the ED, 58.7% of patients were given a short-acting beta-agonist,
      48.9% a short-acting anticholinergic, 27.4% corticosteroids and 19.9%
      antibiotics. Overall, short-acting beta-agonists (63.5%), anticholinergic agents
      (53.4%), corticosteroids (54.5%) and antibiotics (71.1%) were prescribed more
      commonly to discharged patients (p < 0.05 for all). CONCLUSION: We found a low to
      moderate level of adherence to the CTS clinical practice guideline for the
      management of acute exacerbation of COPD in these rural EDs. Moreover, we
      identified gaps in both diagnostic and therapeutic care.

PMID- 25611910
TI  - General practitioner surgery: anyone interested?
AB  - INTRODUCTION: We sought to assess awareness of, exposure to and interest in
      general practitioner (GP) surgery and enhanced surgical skills (ESS) among family
      practice residents in British Columbia, Alberta and Saskatchewan. METHODS: We
      distributed a survey to all family practice residents at 4 universities in BC,
      Alberta and Saskatchewan. The survey assessed demographic information, awareness
      of and exposure to GP surgery or ESS during training, and interest in pursuing
      formal ESS training. RESULTS: We received 174 responses (27.2% response rate).
      Numerous respondents were unaware of GP surgery (9.9% +/- 4.5%) and ESS (17.9% +/
      5.7%). Awareness was higher among respondents from rural hometowns (GP surgery
      and ESS awareness 100% and 94.1%, respectively), and with prior exposure to GP
      surgery (GP surgery and ESS awareness 96.9% and 95.4%, respectively). A minority
      (38.2%) had been exposed to GP surgery, with exposure higher in respondents from
      rural training sites and in their second postgraduate year (72.5% and 47.4%,
      respectively). A quarter (25.1%) of respondents were considering ESS training.
      Factors encouraging training included increased procedures, challenging medicine
      and impact on patient outcomes. The importance of ESS training opportunities and
      service was rated highly. CONCLUSION: Many respondents were unaware of ESS as a
      career option. Exposure to GP surgery during training was associated with
      increased awareness. Furthermore, exposure fostered interest in this important
      field. These results may be helpful in the development of formal ESS training
      programs and in curricula for family practice residency programs.

PMID- 25611911
TI  - The economic contribution of the Northern Ontario School of Medicine to
      communities participating in distributed medical education.
AB  - INTRODUCTION: The economic contribution of medical schools to major urban centres
      can be substantial, but there is little information on the contribution to the
      economy of participating communities made by schools that provide education and
      training away from major cities and academic health science centres. We sought to
      assess the economic contribution of the Northern Ontario School of Medicine
      (NOSM) to northern Ontario communities participating in NOSM's distributed
      medical education programs. METHODS: We developed a local economic model and used
      actual expenditures from 2007/08 to assess the economic contribution of NOSM to
      communities in northern Ontario. We also estimated the economic contribution of
      medical students or residents participating in different programs in communities
      away from the university campuses. To explore broader economic effects, we
      conducted semistructured interviews with leaders in education, health care and
      politics in northern Ontario. RESULTS: The total economic contribution to
      northern Ontario was $67.1 million based on $36.3 million in spending by NOSM and
      $1.0 million spent by students. Economic contributions were greatest in the
      university campus cities of Thunder Bay ($26.7 million) and Sudbury ($30.4
      million), and $0.8-$1.2 million accrued to the next 3 largest population centres.
      Communities might realize an economic contribution of $7300-$103 900 per pair of
      medical learners per placement. Several of the 59 interviewees remarked that the
      dollar amount could be small to moderate but had broader economic implications.
      CONCLUSION: Distributed medical education at the NOSM resulted in a substantial
      economic contribution to participating communities.

PMID- 25611912
TI  - The occasional ED ultrasound: focused assessment with sonography for trauma
      (FAST).

PMID- 25611913
TI  - A plea, an apology and a revelation.

PMID- 25611914
TI  - Social and Economic Aspects of the Transmission of Pathogenic Bacteria between
      Wildlife and Food Animals: A Thematic Analysis of Published Research Knowledge.
AB  - Wildlife is a known reservoir of pathogenic bacteria, including Mycobacterium
      bovis and Brucella spp. Transmission of these pathogens between wildlife and food
      animals can lead to damaging impacts on the agri-food industry and public health.
      Several international case studies have highlighted the complex and cross
      sectoral challenges involved in preventing and managing these potential
      transmission risks. The objective of our study was to develop a better
      understanding of the socio-economic aspects of the transmission of pathogenic
      bacteria between wildlife and food animals to support more effective and
      sustainable risk mitigation strategies. We conducted qualitative thematic
      analysis on a purposive sample of 30/141 articles identified in a complementary
      scoping review of the literature in this area and identified two key themes. The
      first related to the framing of this issue as a 'wicked problem' that depends on
      a complex interaction of social factors and risk perceptions, governance and
      public policy, and economic implications. The second theme consisted of promising
      approaches and strategies to prevent and mitigate the potential risks from
      transmission of pathogenic bacteria between wildlife and food animals. These
      included participatory, collaborative and multidisciplinary decision-making
      approaches and the proactive incorporation of credible scientific evidence and
      local contextual factors into solutions. The integration of these approaches to
      address 'wicked problems' in this field may assist stakeholders and decision
      makers in improving the acceptability and sustainability of future strategies to
      reduce the transmission of pathogenic bacteria between wildlife and food animals.

PMID- 25611915
TI  - Downregulation of ARNT2 promotes tumor growth and predicts poor prognosis in
      human hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) is a
      transcriptional regulator and member of the basic helix-loop-helix/Per-ARNT-SIM
      (bHLH/PAS) superfamily. Recently, evidence of that ARNT is involved in
      carcinogenesis and cancer progression has emerged. The aim of current study was
      to investigate the role of ARNT2, a homolog of ARNT, in tumor growth, invasion,
      and prognosis of hepatocellular carcinoma (HCC). METHODS: Tissue microarray and
      immunohistochemical staining were used to examine the expression of ARNT2 in 195
      HCC tissues. Factors associated with ARNT2 levels were assessed by univariate and
      multivariate Cox regression analyses. Cell proliferation, migration, and invasion
      assays were performed by using ARNT2 silencing and overexpressing HCCLM6 cell
      line. Orthotopic xenograft HCC model was used to elucidate the effects of ARNT2
      on HCC progression in vivo. RESULTS: High intratumoral of ARNT2 level was well
      correlated with longer overall survival (OS) and lower tumor to recurrence (TTR)
      of HCC patients after resection. Multivariate analysis revealed that intratumoral
      ARNT2 overexpression was an independent prognostic factor for both OS and TTR.
      Knockdown of ARNT2 in HCCLM6 cells was significantly enhanced while
      overexpression of ARNT2 significantly inhibited the ability of cell
      proliferation, invasion, and migration. In animal studies, downregulation of
      ARNT2 in HCCLM6 cells promoted, whereas upregulation of ARNT2 in HCCLM6 cells
      reduced HCCLM6 growth in vivo. CONCLUSIONS: Our data demonstrate that ARNT2 plays
      an inhibitory role in HCC progression and suggest that ARNT2 may be a potential
      prognostic predictor and therapeutic target for HCC.

PMID- 25611919
TI  - Immunoregulatory actions of melatonin and zinc during chronic Trypanosoma cruzi
      infection.
AB  - After one century of the discovery of Chagas' disease and the development of an
      efficient drug with amplitude of actions both in the acute and chronic phase is
      still a challenge. Alternative immune modulators have been exhaustively used. For
      that purpose, melatonin and zinc were administered during chronic Trypanosoma
      cruzi-infected Wistar rats and several endpoints were assessed. Melatonin has a
      remarkable functional versatility, being associated with important antioxidant,
      anti-inflammatory, and anti-apoptotic effects. The cross-talk between zinc and
      the immune system includes its ability to influence the production and signaling
      of numerous inflammatory cytokines in a variety of cell types. Our study showed
      that zinc triggered a decrease in the generation of IFN-gamma for TCD4(+) cells.
      Reduced percentage of CD4(+) T cells producing TNF-alpha was observed in control
      melatonin or zinc-and-melatonin-treated animals as compared with untreated rats.
      On the other hand, a significant increase in the percentage of IL-4 from CD4(+)
      and CD8(+) T lymphocytes producers was observed 60 days after infection, for all
      zinc-treated animals, whether infected or not. Melatonin and zinc therapies
      increased the percentages of CD4(+) and CD8(+) T lymphocytes IL-10 producers.
      CD4(+) CD25(high) Foxp3(+) T cells were also elevated in zinc- and melatonin
      treated animals. The modulation of the immune system influenced by these
      molecules affected cytokine production and the inflammatory process during
      chronic T. cruzi infection. Elucidation of the interplay between cytokine balance
      and the pathogenesis of Chagas' disease is extremely relevant not only for the
      comprehension of the immune mechanisms and clinical forms but, most importantly,
      also for the implementation of efficient and adequate therapies. 

PMID- 25611918
TI  - Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis.
AB  - BACKGROUND: Metabolomic evaluation of cystic fibrosis (CF) airway secretions
      could identify metabolites and metabolic pathways involved in neutrophilic airway
      inflammation that could serve as biomarkers and therapeutic targets. METHODS:
      Mass spectrometry (MS)-based metabolomics was performed on a discovery set of BAL
      fluid samples from 25 children with CF, and targeted MS methods were used to
      identify and quantify metabolites related to neutrophilic inflammation. A
      biomarker panel of these metabolites was then compared with neutrophil counts and
      clinical markers in independent validation sets of lavage from children with CF
      and adults with COPD compared with control subjects. RESULTS: Of the 7,791
      individual peaks detected by positive-mode MS metabolomics discovery profiling,
      338 were associated with neutrophilic inflammation. Targeted MS determined that
      many of these peaks were generated by metabolites from pathways related to the
      metabolism of purines, polyamines, proteins, and nicotinamide. Analysis of the
      independent validation sets verified that, in subjects with CF or COPD, several
      metabolites, particularly those from purine metabolism and protein catabolism
      pathways, were strongly correlated with neutrophil counts and were related to
      clinical markers, including airway infection and lung function. CONCLUSIONS: MS
      metabolomics identified multiple metabolic pathways associated with neutrophilic
      airway inflammation. These findings provide insight into disease pathophysiology
      and can serve as the basis for developing disease biomarkers and therapeutic
      interventions for airways diseases.

PMID- 25611920
TI  - Endoscopic ultrasonography using new functions for pancreatobiliary diseases:
      current status and future perspectives.
AB  - A new endoscopic ultrasound processor (EU-ME2 Premier Plus) has recently been
      developed. It improves fundamental imaging and enables three new functions;
      namely, tissue harmonic echo (THE), elastography, and contrast harmonic
      endoscopic ultrasonography (CH-EUS). However, many aspects regarding the
      usefulness of these three functions in the diagnosis of pancreatobiliary diseases
      remain unknown. In connection with and prior to the convening of Endoscopy Forum
      Japan 2014, endoscopic ultrasonography using EU-ME2 Premier Plus was carried out
      for pancreatic, bile duct, and gallbladder cases at 12 participating institutions
      (Japan [n = 10]; other Asian countries [n = 2]). A questionnaire survey was
      conducted regarding the usefulness of EU-ME2 Premier Plus for each EUS case. In
      addition, participants' views were surveyed by asking them to vote as to whether
      or not the three functions of EU-ME2 Premier Plus were useful for several items
      under pancreatic, bile duct, and gallbladder indications. According to the
      participants' views, THE (particularly THE-P mode) is essential for the diagnosis
      of cystic lesions. Many participants viewed elastography as useful in only
      extremely limited cases. Although CH-EUS was not considered useful for all cases,
      its indications covered a broad range. Additional studies are warranted to
      clarify the functions of EU-ME2 Premier Plus in more detail.

PMID- 25611921
TI  - Emergency surgery for PPH in women declining blood transfusion or when allogeneic
      blood is not available.

PMID- 25611922
TI  - microRNA expression in the cervix during pregnancy is associated with length of
      gestation.
AB  - Preterm birth is a leading cause of infant mortality and can lead to poor life
      long health and adverse neurodevelopmental outcomes. The pathophysiologic
      mechanisms that precede preterm labor remain elusive, and the role that
      epigenetic phenomena play is largely unstudied. The objective of this study was
      to assess the association between microRNA (miRNA) expression levels in cervical
      cells obtained from swabs collected during pregnancy and the length of gestation.
      We analyzed cervical samples obtained between 16 and 19 weeks of gestation from
      53 women in a prospective cohort from Mexico City, and followed them until
      delivery. Cervical miRNA was extracted and expression was quantified using the
      NanoString nCounter Analysis System. Linear regression models were used to
      examine the association between miRNA expression levels and gestational age at
      delivery, adjusted for maternal age, education, parity, body mass index, smoke
      exposure, and inflammation assessed on a Papanicolaou smear. We identified 6
      miRNAs that were significantly associated with gestational age at the time of
      delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each
      doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2-1.5) days shorter
      on average (P = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223
      expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of
      the miRNAs were enriched for molecules involved in DNA replication and
      inflammatory processes. The levels of specific miRNAs in the human cervix during
      pregnancy are predictive of gestational age at delivery, and should be validated
      in future studies as potential biomarkers of preterm birth risk.

PMID- 25611923
TI  - Photoluminescence enhancement in Na3SO4Cl:X (X = Ce3+, Eu3+ or Dy3+) material.
AB  - The compound Na3SO4Cl X (X = Ce(3+), Eu(3+) or Dy(3+)) prepared by the wet
      chemical method was studied for its photoluminescence (PL) and energy transfer
      characteristics. The PL from Na3 SO4 Cl:Ce(3+) shows strong emission at 322 nm at
      an excitation of 272 nm. Therefore, an efficient Ce(3+) -> Dy(3+), Eu(2+) ->
      Dy(3+) and Eu(2+) -> Eu(3+) energy transfer had taken place in this host. The
      Dy(3+) emission caused by Ce(3+) -> Dy(3+) energy transfer under ultraviolet (UV)
      wavelengths peaked at around 477 nm and 572 nm due to (4) F9/2 -> (6) H15/2 and
      (6) H13/2 transitions with yellow-orange emission in the Na3 SO4 Cl lattice. An
      intense Dy(3+) emission was observed at 482 and 576 nm caused by the Eu(2+) ->
      Dy(3+) energy transfer process and due to (4) F9/2 -> (6) H15/2 and (4) F9/2 ->
      (6) H13/2 transitions respectively. The Eu(3+) blue to red light emission caused
      by the Eu(2+) -> Eu(3+) energy transfer peaked at 593 nm and 617 nm due to (5) D0
      -> (5) D3 transitions. The presence of trivalent Eu in Na3 SO4 Cl suggested the
      presence of Eu(3+) in the host compound that occupied two different lattice sites
      and that peaked at 593 and 617 nm due to (5) D0 -> (7) F1 and (5) D0 -> (7) F2
      transitions respectively. The trivalent europium ion is very useful for studying
      the nature of metal coordination in various systems due to its non-degenerate
      emitting (5) D0 state. The present paper discusses the photoluminescence
      characteristics of Eu(2+) -> Dy(3+) and Eu(2+) -> Eu(3+) energy transfer. This
      compound may be useful as a lamp phosphor.

PMID- 25611924
TI  - Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood
      DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A
      Pilot Study.
AB  - PURPOSE/AIM: To compare the plasma levels of homocysteine and asymmetrical
      dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in
      patients with early and neovascular age-related macular degeneration (AMD) and in
      controls without maculopathy of any sort. MATERIALS AND METHODS: This
      observational case-control pilot study included 39 early AMD patients, 27
      neovascular AMD patients and 132 sex- and age-matched controls without
      maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole
      blood DNA methylation were measured. Quantitative variables were compared by
      Student's t-test or Mann-Whitney test. Logistic regression models were used to
      investigate the significance of the association between early or wet AMD and some
      variables. RESULTS: There were no significant differences in mean plasma
      homocysteine and ADMA concentrations and in the degree of whole blood DNA
      methylation between patients with early or neovascular AMD and their controls.
      Similarly, logistic regression analysis disclosed that plasma homocysteine and
      ADMA levels were not associated with an increased risk for early or neovascular
      AMD. CONCLUSIONS: We failed to demonstrate an association between early or
      neovascular AMD and increased plasma homocysteine and/or ADMA. Results also
      suggest that the degree of whole blood DNA methylation is not a marker of AMD.

PMID- 25611926
TI  - Special section: Social change, cultural evolution and human development.

PMID- 25611927
TI  - The decline of cooperation, the rise of competition: developmental effects of
      long-term social change in Mexico.
AB  - Using Greenfield's theory of sociocultural change and human development as a
      point of departure, we carried out two experimental studies exploring the
      implications of decades of globalised social change in Mexico for children's
      development of cooperation and competition. In rural San Vicente, Baja
      California, the baseline was 1970 and the historical comparison took place 40
      years later. In Veracruz, the baseline was 1985 and the historical comparison
      took place 20 years later. In Veracruz, children were tested in both rural and
      urban settings. We hypothesized that cooperative behavior would decrease in all
      three settings as a result of the sociocultural transformations of the past
      decades in Mexico. The Madsen Marble Pull Game was used to assess cooperative and
      competitive behavior. As predicted by Greenfield's theory of social change and
      human development, the Marble Pull procedure revealed a striking decrease over
      time in levels of cooperative behavior, with a corresponding rise in competitive
      behavior, in all three settings. 

PMID- 25611928
TI  - Cultural evolution over the last 40 years in China: using the Google Ngram Viewer
      to study implications of social and political change for cultural values.
AB  - Chinese people have held collectivistic values such as obligation, giving to
      other people, obedience and sacrifice of personal interests for thousands of
      years. In recent decades, China has undergone rapid economic development and
      urbanisation. This study investigates changing cultural values in China from 1970
      to 2008 and the relationship of changing values to ecological shifts. The
      conceptual framework for the study was Greenfield's (2009) theory of social
      change and human development. Changing frequencies of contrasting Chinese words
      indexing individualistic or collectivistic values show that values shift along
      with ecological changes (urbanisation, economic development and enrollment in
      higher education), thereby adapting to current sociodemographic contexts. Words
      indexing adaptive individualistic values increased in frequency between 1970 and
      2008. In contrast, words indexing less adaptive collectivistic values either
      decreased in frequency in this same period of time or else rose more slowly than
      words indexing contrasting individualistic values. 

PMID- 25611929
TI  - Big Five personality traits: are they really important for the subjective well
      being of Indians?
AB  - This study empirically examined the relationship between the Big Five personality
      traits and subjective well-being (SWB) in India. SWB variables used were life
      satisfaction, positive affect and negative affect. A total of 183 participants in
      the age range 30-40 years from Pune, India, completed the personality and SWB
      measures. Backward stepwise regression analysis showed that the Big Five traits
      accounted for 17% of the variance in life satisfaction, 35% variance in positive
      affect and 28% variance in negative affect. Conscientiousness emerged as the
      strongest predictor of life satisfaction. In line with the earlier research
      findings, neuroticism and extraversion were found to predict negative affect and
      positive affect, respectively. Neither openness to experience nor agreeableness
      contributed to SWB. The research emphasises the need to revisit the association
      between personality and SWB across different cultures, especially non-western
      cultures. 

PMID- 25611930
TI  - Perception of parents as demonstrating the inherent merit of their values:
      relations with self-congruence and subjective well-being.
AB  - This study focuses on the parenting practice of inherent value demonstration
      (IVD), involving parents' tendency to express their values in behaviours and
      appear satisfied and vital while doing so. Data from Chinese college students (n
      = 89) confirmed the hypothesis that offspring's perception of their parents as
      engaged in IVD predicts offspring's subjective well-being (SWB) through sense of
      self-congruence. Importantly, these relations emerged also when controlling for
      fundamental autonomy-supportive (FAS) parenting practices such as taking
      children's perspective, minimising control and allowing choice. These findings
      are consistent with the view that parents concerned with their children's sense
      of autonomy may do well to engage in IVD in addition to more fundamental autonomy
      supportive practices. Future research may examine the role of IVD in promoting
      authentic values that serve as an internal compass that guides children to act in
      ways that feel self-congruent. 

PMID- 25611931
TI  - Does red undermine individuals' intellectual performance? A test in China.
AB  - Previous research shows that red impairs individuals' performance on challenging
      intellectual tasks in achievement situations. However, no research to date has
      examined this issue in Chinese society. In China, red has a positive connotation
      in general (unlike in the West), but also has a negative connotation for
      students, given that teachers mark incorrect answers in red (like in the West).
      Therefore, the question of whether red promotes or undermines intellectual
      performance for Chinese individuals needs to be tested. The present research
      investigated this and found, consistent with findings obtained in the West, that
      red undermined the intellectual performance of Chinese students. Future
      directions and potential mechanisms are discussed. 

PMID- 25611932
TI  - The feasibility of an e-mail-delivered intervention to improve nutrition and
      physical activity behaviors in African American college students.
AB  - OBJECTIVES: To evaluate the feasibility and acceptability of an e-mail-delivered
      program to promote nutrition and physical activity in African American college
      students. PARTICIPANTS: Forty-seven students (76% female, aged 18-20 years).
      METHODS: Students participated in a 24-week randomized controlled trial,
      receiving either general health information or the intervention focused on diet
      and physical activity. RESULTS: At baseline, 80.9% and 76.0% of participants
      reported interest in improving diet and physical activity, respectively.
      Participants evidenced poor nutrition behaviors and 46% were overweight or obese.
      At 24 weeks, most participants (70% control, 84% intervention) were "somewhat" or
      "very" satisfied with the program. The program was feasible to administrate, with
      the exception of measurement of physical activity using accelerometers.
      CONCLUSIONS: An innovative e-mail-delivered program promoting positive health
      behaviors appears to be feasible and acceptable in African American college
      students. Further research is needed to evaluate program efficacy in this
      population, including prevention of excess weight gain.

PMID- 25611933
TI  - IL-17A-producing CD8(+)T cells as therapeutic targets in autoimmunity.
AB  - INTRODUCTION: The involvement of IL-17-producing CD8(+)T cells (TC17) in various
      conditions, such as infection, cancer and autoimmune inflammation, has been
      documented in both humans and mice; however, TC17 cells have received only
      marginal attention. AREAS COVERED: Here, we provide an overview of the cytokines,
      chemokines, and cytokine and chemokine receptors that characterize the murine and
      human TC17 cell phenotype. We also discuss signaling pathways, molecular
      interactions, and transcriptional and epigenetic events that contribute to TC17
      differentiation and acquisition of effector functions. Heterogeneity and inherent
      phenotypic instability of TC17 cells were shown both in humans and murine models.
      Aberrant expression of TC17 cells was observed in many autoimmune conditions.
      Moreover, functional analysis demonstrated in vivo plasticity of TC17 cells may
      be a key feature of TC17 cell biology in autoimmune diseases. EXPERT OPINION: Due
      to its important roles in inflammation and autoimmunity, TC17 cell pathway may
      have promise as a potential therapeutic target for autoimmune diseases. The
      strategies include the suppression of TC17 cell generation and migration and the
      blockade of TC17 cell instability and heterogeneity. TMP778 may open an avenue to
      novel therapeutic strategies.

PMID- 25611935
TI  - Physical activity in physical education: are longer lessons better?
AB  - BACKGROUND: The purpose of this study was to compare physical activity (PA)
      outcomes in a sample of high school (HS) physical education (PE) lessons from
      schools that adopted traditional versus modified block schedule formats. METHODS:
      We used the System for Observing Fitness Instruction Time (SOFIT) to conduct
      observations of 168 HS PE lessons delivered by 22 PE teachers in 4 schools. T
      tests and multilevel models were used to explore variability in moderate PA and
      vigorous PA. RESULTS: PA outcomes were significantly different between modified
      block and traditional schools. Students who attended traditional schools engaged
      in more vigorous PA in PE lessons. Modified block lessons lost more scheduled
      lesson time due to poor transition to and from the locker room. PA outcomes were
      positively associated with fitness and teacher promotion of PA and negatively
      associated with lost time, class size, management, and knowledge. CONCLUSIONS:
      Although PE proponents widely advocate for more PE minutes, this study showed
      that greater time scheduled in PE does not necessarily result in more student
      accrual of moderate to vigorous physical activity (MVPA) minutes.

PMID- 25611934
TI  - hnRNP K coordinates transcriptional silencing by SETDB1 in embryonic stem cells.
AB  - Retrotransposition of endogenous retroviruses (ERVs) poses a substantial threat
      to genome stability. Transcriptional silencing of a subset of these parasitic
      elements in early mouse embryonic and germ cell development is dependent upon the
      lysine methyltransferase SETDB1, which deposits H3K9 trimethylation (H3K9me3) and
      the co-repressor KAP1, which binds SETDB1 when SUMOylated. Here we identified the
      transcription co-factor hnRNP K as a novel binding partner of the SETDB1/KAP1
      complex in mouse embryonic stem cells (mESCs) and show that hnRNP K is required
      for ERV silencing. RNAi-mediated knockdown of hnRNP K led to depletion of H3K9me3
      at ERVs, concomitant with de-repression of proviral reporter constructs and
      specific ERV subfamilies, as well as a cohort of germline-specific genes directly
      targeted by SETDB1. While hnRNP K recruitment to ERVs is dependent upon KAP1,
      SETDB1 binding at these elements requires hnRNP K. Furthermore, an intact SUMO
      conjugation pathway is necessary for SETDB1 recruitment to proviral chromatin and
      depletion of hnRNP K resulted in reduced SUMOylation at ERVs. Taken together,
      these findings reveal a novel regulatory hierarchy governing SETDB1 recruitment
      and in turn, transcriptional silencing in mESCs. 

PMID- 25611936
TI  - Does a higher incidence of break times in primary schools result in children
      being more physically active?
AB  - BACKGROUND: Regular physical activity (PA) has multiple benefits to health;
      however, the majority of schoolchildren do not reach PA guidelines of 60 minutes
      of moderate to vigorous PA (MVPA) daily. During the school day, break times are
      often the only opportunity for children to be physically active. This study
      investigated PA levels during school breaks in German primary school children.
      METHODS: PA of 294 children (7.1 +/- 0.7 years; 48% boys) was assessed. On the
      basis of timetables, individual activity times and intensities for daily breaks
      were determined. Children's weight status was determined on site. RESULTS: Breaks
      lasted 30.7 (+/- 13.8) minutes; length varied significantly between 1 and 2
      breaks (21.7 +/- 4.1 versus 36.2 +/- 14.8 minutes; p <= .01). Children spent
      25.3% of their breaks in MVPA, boys being significantly more active (30.8% versus
      20.4%; p <= .01). Time spent in MVPA differed significantly between normal weight
      and overweight/obese children (26.1% versus 18.4%; p <= .05). Children having 2
      breaks engaged in significantly more MVPA than those with only 1 (7.4 +/- 6.1
      versus 5.6 +/- 4.7 minutes; p <= .02). CONCLUSIONS: Children spent 25% of their
      break in MVPA; having 2 breaks increased time in MVPA significantly, although
      this is also influenced by weight status. Consequently, more activity breaks
      should be scheduled during school hours.

PMID- 25611937
TI  - Association of school social networks' influence and mass media factors with
      cigarette smoking among asthmatic students.
AB  - BACKGROUND: Around 10% of adolescent students under 18 years have current asthma.
      Asthmatic adolescents smoke as much or more than non-asthmatic adolescents. We
      explored the association between exposure to mass media and social networks'
      influence with asthmatic student smoking, and variations of these exposures by
      sex. METHODS: This study included 9755 asthmatic and 38,487 non-asthmatic middle
      and high school students. Secondary data analysis incorporated the complex sample
      design; and univariate, bivariate, and logistic regression statistics. RESULTS:
      Asthmatic students had greater odds of smoking than non-asthmatic students.
      Asthmatic female students were more likely than asthmatic male students to have
      been exposed to secondhand smoke in rooms or cars and to smoking actors, but less
      likely to associate smoking with intent to wear tobacco-marketing products, or
      with looking cool/fitting in. Asthmatic male and female students, who have
      smoking friends, were exposed to secondhand smoke in rooms (only girls) or cars,
      intended to smoke if best friends offered cigarettes, or received/bought tobacco
      marketing products had greater odds of smoking than other asthmatic students.
      CONCLUSIONS: The observed associations suggest the need for general interventions
      to reduce middle and high school students' cigarette smoking as well as targeted
      interventions for asthmatic adolescent students.

PMID- 25611938
TI  - The source and impact of appearance teasing: an examination by sex and weight
      status among early adolescents from the Czech Republic.
AB  - BACKGROUND: Some adolescents are victims of negative appearance-related feedback,
      and this may have lasting adverse effects on their self-evaluation. The aim of
      this study was to examine the frequency and impact of appearance teasing across
      sex and weight status. METHODS: The participants were 570 Czech adolescents
      (47.9% girls) evaluated at age 13 during the European Longitudinal Study of
      Pregnancy and Childhood. Instruments used were body mass index and an adapted
      version of the Physical Experiences Survey that measures appearance teasing
      sources (parents, peers, among others), body part teased, and the impact of
      teasing. Chi-square test and multivariate analyses of variance were conducted to
      compare groups by sex and weight status. Logistic regression was then used for
      adjusted analyses. RESULTS: Girls were more likely to report appearance teasing
      than boys. Overweight adolescents, both girls and boys, were more likely to be
      teased than non-overweight adolescents. Overweight adolescents compared with non
      overweight adolescents reported higher levels of impact of body-related teasing.
      CONCLUSIONS: Czech adolescents continue to adopt the societal standards of
      Western countries, stigmatizing overweight peers. This may affect more obese
      adolescents. Future research has to evaluate different sources of appearance
      related teasing. Interventions in schools are suitable for the reduction of
      appearance-related prejudices.

PMID- 25611939
TI  - The impact of playworks on boys' and girls' physical activity during recess.
AB  - BACKGROUND: School-based programs, such as Playworks, that guide students in
      organized activities during recess and make improvements to the recess play yard
      may lead to significant increases in physical activity-especially for girls. This
      study builds on past research by investigating the impact of Playworks separately
      for girls and boys. METHODS: Twenty-nine schools were randomly assigned to
      receive Playworks for 1 school year or serve as a control group. Postintervention
      physical activity data were collected via accelerometers and recess observations.
      Impacts were estimated separately for girls and boys using regression models.
      RESULTS: Girls in Playworks schools had significantly higher accelerometer
      intensity counts and spent more time in vigorous physical activity than girls in
      control schools. No significant differences based on accelerometer data were
      found for boys. A significant impact was also found on the types of activities in
      which girls engaged during recess; girls in the treatment group were less likely
      than those in the control group to be sedentary and more likely to engage in
      jumping, tag, and playground games. CONCLUSIONS: The current findings suggest
      that Playworks had a significant impact on some measures of girls' physical
      activity, but no significant impact on measures of boys' physical activity.

PMID- 25611940
TI  - Developing a comprehensive school connectedness scale for program evaluation.
AB  - BACKGROUND: Evidence show that school connectedness is important to youth
      wellness. However, considerable inconsistency in the concepts and measures of
      school connectedness exists across studies. In addition, many measures do not
      capture the multifaceted dimensions of the school connectedness construct. This
      study examined the psychometric properties of a school connectedness scale that
      aimed to measure comprehensively the key constructs of school connectedness.
      METHODS: The scale was developed with teachers and tested with an ethnically
      diverse sample of 717 high school students enrolled in a school connectedness
      course using confirmatory factor analysis. RESULTS: Confirmatory factor analyses
      demonstrated the association of the 15 items with the 5 factors identified in the
      literature-school involvement, academic motivation, school attachment, teacher
      support, and peer relations (chi(2) = 439.99, df = 83, p < .0001, Comparative Fit
      Index = 0.991, Tucker-Lewis index = 0.988, root mean square error of
      approximation = 0.077). Cronbach coefficient alphas for the factors ranged from
      0.73 to 0.93. CONCLUSIONS: Although further tests need to be conducted to assess
      its validity and reliability, this newly developed scale may provide researchers
      a tool to measure comprehensively school connectedness for program evaluation.

PMID- 25611941
TI  - Effectiveness of health education teachers and school nurses teaching sexually
      transmitted infections/human immunodeficiency virus prevention knowledge and
      skills in high school.
AB  - BACKGROUND: We examined the differential impact of a well-established human
      immunodeficiency virus (HIV)/sexually transmitted infections (STIs) curriculum,
      Be Proud! Be Responsible!, when taught by school nurses and health education
      classroom teachers within a high school curricula. METHODS: Group-randomized
      intervention study of 1357 ninth and tenth grade students in 10 schools. Twenty
      seven facilitators (6 nurses, 21 teachers) provided programming; nurse-led
      classrooms were randomly assigned. RESULTS: Students taught by teachers were more
      likely to report their instructor to be prepared, comfortable with the material,
      and challenged them to think about their health than students taught by a school
      nurse. Both groups reported significant improvements in HIV/STI/condom knowledge
      immediately following the intervention, compared to controls. Yet, those taught
      by school nurses reported significant and sustained changes (up to 12 months
      after intervention) in attitudes, beliefs, and efficacy, whereas those taught by
      health education teachers reported far fewer changes, with sustained improvement
      in condom knowledge only. CONCLUSIONS: Both classroom teachers and school nurses
      are effective in conveying reproductive health information to high school
      students; however, teaching the technical (eg, condom use) and interpersonal (eg,
      negotiation) skills needed to reduce high-risk sexual behavior may require a
      unique set of skills and experiences that health education teachers may not
      typically have.

PMID- 25611942
TI  - Walking school buses as a form of active transportation for children-a review of
      the evidence.
AB  - BACKGROUND: Walking school buses (WSBs) offer a potentially healthier way for
      children to get to school while reducing traffic congestion. A number of pressing
      societal challenges make it timely to evaluate evidence of their value. METHODS:
      Studies that focused solely on WSBs were identified through online and manual
      literature searches. Twelve WSB studies involving a total of 9169 children were
      reviewed. Study aims, designs, methods, outcomes, and barriers and facilitators
      were examined. RESULTS: WSBs were found to be associated with increased
      prevalence of walking to school and general activity levels although not always
      significantly. Time constraints emerged as barriers to WSBs, impacting on
      recruitment of volunteers and children to the WSBs. Facilitators of WSBs included
      children enjoying socializing and interacting with the environment. CONCLUSIONS:
      Preliminary evidence of the health value of WSBs was demonstrated, along with
      recommendations for the design of future studies. By tackling barriers of time
      constraints, volunteer recruitment, and parents' safety concerns while at the
      same time, increasing convenience and time savings for families, future WSBs are
      likely to be more sustainable and taken up by more schools. Implications for
      future innovation in school health were identified.

PMID- 25611944
TI  - Effects of a 2-year behavioral weight loss intervention on sleep and mood in
      obese individuals treated in primary care practice.
AB  - OBJECTIVE: To examine the effect of weight loss on sleep duration, sleep quality,
      and mood in 390 obese men and women who received one of three behavioral weight
      loss interventions in the Practice-based Opportunities for Weight Reduction trial
      at the University of Pennsylvania (POWER-UP). METHODS: Sleep duration and quality
      were assessed at baseline and months 6 and 24 by the Pittsburgh Sleep Quality
      Index (PSQI) questionnaire and mood by the Patient Health Questionnaire-8 (PHQ
      8). Changes in sleep and mood were examined according to treatment group and
      based on participants' having lost >=5% of initial weight vs. <5%. RESULTS: There
      were few significant differences between treatment groups in changes in sleep or
      mood. At month 6, however, mean (+/-SD) min of sleep increased significantly more
      in participants who lost >=5% vs. <5% (21.6 +/- 7.2 vs. 1.2 +/- 6.0 min, P =
      0.0031). PSQI total scores similarly improved (declined) more in those who lost
      >=5% vs. <5% (-1.2 +/- 0.2 vs. -0.4 +/- 0.2, P < 0.001), as did PHQ-8 scores (
      2.5 +/- 0.4 vs. -0.1 +/- 0.3, P < 0.0001). At month 24, only the differences in
      mood remained statistically significant (P < 0.05). CONCLUSION: Losing >=5% of
      initial weight was associated with short-term improvements in sleep duration and
      sleep quality, as well as favorable short- and long-term changes in mood.

PMID- 25611945
TI  - Endocrine-disrupting potentials of equine estrogens equilin, equilenin, and their
      metabolites, in the medaka Oryzias latipes: in silico and DNA microarray studies.
AB  - Although several previous studies have demonstrated the presence of equine
      estrogens in the aquatic environment, limited data are currently available on the
      endocrine-disrupting potentials in fish and the risks they pose to aquatic
      organisms. To investigate the interactions of major equine estrogens equilin (Eq)
      and equilenin (Eqn), as well as their metabolites 17alpha-dihydroequilin, 17beta
      dihydroequilin, 17alpha-dihydroequilenin and 17beta-dihydroequilenin, with the
      estrogen receptor alpha (ERalpha) of medaka (Oryzias latipes), a three
      dimensional model of the ligand-binding domain (LBD) of ERalpha was built in
      silico, and docking simulations were performed. The docking simulation analysis
      indicated that the interaction of 17beta-dihydroequilenin with the ERalpha LBD is
      the most potent, followed by those of 17alpha-dihydroequilin and 17beta
      dihydroequilin, whereas those of Eq and Eqn were least potent. We further
      analyzed gene expression profiles in the livers of male medaka exposed to Eq and
      Eqn. A DNA microarray representing 6000 genes revealed that 24-h exposure to Eq
      and Eqn (100 ng/L) upregulated the expression of 6 and 34 genes in the livers of
      males, respectively. Genes upregulated by Eq included the estrogenic biomarker
      genes vitellogenins and choriogenins, suggesting the estrogenic potential of Eq.
      In contrast, Eqn exposure upregulated several cancer-related genes, such as
      mediator complex subunit 16 and RAS oncogene family members, suggesting a
      carcinogenic potential for Eqn. These results suggest that equine estrogens may
      have not only endocrine-disrupting potentials via the ERalpha signaling pathway
      but also carcinogenic potency in male medaka.

PMID- 25611943
TI  - Cancer-related information needs and cancer's impact on control over life
      influence health-related quality of life among adolescents and young adults with
      cancer.
AB  - OBJECTIVE: Adolescents and young adults (AYAs) diagnosed with cancer between 15
      and 39 years of age often report need for greater amounts of cancer-related
      information and perceive that cancer has had a negative impact on control over
      their life. We examined whether unmet information need and perceived control over
      life are associated with health-related quality of life (HRQOL). METHODS: We
      examined data from 484 AYA cancer survivors recruited from population-based
      cancer registries in 2007-2008. Participants completed surveys a median of 11
      months after diagnosis. Multivariable linear regression analyses estimated
      associations of unmet cancer-related information needs and impact of cancer on
      control over life on HRQOL (SF-12). RESULTS: Two-thirds of AYAs reported an
      intermediate or high level of unmet information need, and half (47%) reported a
      negative impact of cancer on control. Greater unmet information need was
      associated with lower overall mental and physical HRQOL and lower levels of all
      HRQOL subscales except vitality. A negative impact on control over life was
      associated with lower overall mental HRQOL as well as lower HRQOL across all
      subscales except general health perceptions (all p <0.05). In multivariable
      analyses, perceived control and unmet information need were independently
      associated with HRQOL (p-values for interaction >0.1). CONCLUSIONS: Adolescent
      and young adult patients with cancer have high levels of unmet cancer-related
      information needs and perceived negative impact of cancer on control over life;
      both were independently associated with lower HRQOL. Addressing unmet information
      needs among AYA cancer survivors and finding ways to increase their sense of
      control may help improve HRQOL in this understudied population.

PMID- 25611946
TI  - Quantitative analysis of human parvovirus B19 DNA in maternal and fetal serum,
      and amniotic fluid during an early stage of pregnancy.
AB  - Simple and accurate diagnosis of vertical transmission of human parvovirus B19
      (B19V) infection remains an important issue in pregnancy. There are few reports
      on quantitative analysis of B19V in amniotic fluids. Quantitative estimation of
      B19V DNA in amniotic fluids was comparerd with those in maternal or fetal serum
      obtained at an early stage of pregnancy with possible mother-to-fetus
      transmission. All pregnant women contracted B19V infection between 13 to 14 weeks
      gestation. The B19V DNA amount in 3 maternal serum and amniotic fluid sample
      pairs collected between 16 to 27 weeks gestation was quantified by a real-time
      polymerase chain reaction assay. Serum from 2 fetuses was included. The B19V DNA
      concentrations in maternal sera and amniotic fluids ranged from 10(4) to 10(5)
      copies/ml and from 10(7) to 10(8) copies/ml, respectively. The B19V DNA in the
      amniotic fluids concentration coincided with those of each fetal serum. The
      concentrations in amniotic fluids are 100 to 5,000 times higher than in those of
      maternal sera, and corresponded to the matching fetal serum. Amniotic fluids may
      substitute for the fetal sera in terms of quantitative estimation of fetal B19V
      infection at an early stage of pregnancy.

PMID- 25611947
TI  - Cellulose-based filter aids increase the capacity of depth filters during the
      downstream processing of plant-derived biopharmaceutical proteins.
AB  - Downstream processing (DSP) is a major cost factor during the production of
      biopharmaceutical proteins. Clarification can account for ~40% of these costs,
      especially when a large amount of dispersed particulate material is generated,
      such as during the extraction of intracellular proteins from plants. Filter
      capacity can be increased (and DSP costs reduced) by using flocculants. Here we
      show that cellulose-based filter aids can enhance the positive effect of
      flocculants by improving depth filter capacity even further. A design-of
      experiments (DoE) approach was used to identify the optimal size and
      concentration of filter aids, at different values of pH and conductivity, for the
      clarification of tobacco leaf extracts during the production of a monoclonal
      antibody and a fluorescent protein. Filter aids ~28 or ~100 MUm in length at
      concentrations of ~10 and ~5 g L(-1) respectively were most efficient in
      combination with a strong cationic flocculant, but were ineffective without the
      flocculant. The filter aids increased depth filter capacity by 35-fold compared
      to an additive-free extract reaching ~1000 L m(-2) without affecting the target
      proteins. Thus, filter aids can be used to reduce production costs of plant
      derived biopharmaceuticals while the DoE approach enabled the identification of
      robust process conditions. 

PMID- 25611948
TI  - Remarkably enhanced gas separation by partial self-conversion of a laminated
      membrane to metal-organic frameworks.
AB  - Separation methods based on 2D interlayer galleries are currently gaining
      widespread attention. The potential of such galleries as high-performance gas
      separation membranes is however still rarely explored. Besides, it is well
      recognized that gas permeance and separation factor are often inversely
      correlated in membrane-based gas separation. Therefore, breaking this trade-off
      becomes highly desirable. Here, the gas-separation performance of a 2D laminated
      membrane was improved by its partial self-conversion to metal-organic frameworks.
      A ZIF-8-ZnAl-NO3 layered double hydroxide (LDH) composite membrane was thus
      successfully prepared in one step by partial conversion of the ZnAl-NO3 LDH
      membrane, ultimately leading to a remarkably enhanced H2 /CH4 separation factor
      and H2 permeance. 

PMID- 25611949
TI  - Occupational exposures and risk of stomach and esophageal cancers: update of a
      cohort of female textile workers in Shanghai, China.
AB  - BACKGROUND: Associations between stomach and esophageal cancer and exposures to
      dusts, metals, chemicals, and endotoxin in the workplace are not very well
      understood, particularly in women. METHODS: We followed 267,400 female textile
      workers in Shanghai, China for cancer incidence from 1989 to 2006. Stomach (n =
      1374) and esophageal (n = 190) cancer cases were identified and a comparison
      subcohort (n = 3187) was randomly selected. Cox proportional hazard modeling was
      used, adjusting for age and smoking. RESULTS: Increasing stomach cancer risk was
      observed with increasing duration of synthetic fiber dust exposure (p = 0.03),
      although the magnitude of effect was small (20 + years: HR = 1.2, 95% CI 1.1
      1.4). Trends with endotoxin exposure were modestly inversed for esophageal cancer
      and increased for stomach cancer, but with little deviation from a null
      association. CONCLUSIONS: Our findings demonstrate that long durations of
      synthetic fiber dust exposure can increase stomach cancer risk in women, but
      provide limited support for associations with other textile industry exposures.

PMID- 25611950
TI  - Association between knee pain and gait speed decline in rural Japanese community
      dwelling older adults: 1-year prospective cohort study.
AB  - AIM: The present study examined whether knee pain was associated with decline in
      maximum gait speed (MGS) in a rural mountainous region. METHODS: This was a
      population-based 1-year prospective cohort study. A total of 658 men and women
      aged 60 years and older participated in the baseline survey in 2006, and 400
      individuals participated in the follow-up survey in 2007. We compared the
      incidence of meaningful decline in gait speed (>=0.1 m/s) in older adults with
      different knee pain levels (none, mild, severe), estimating incidence rate ratio
      (IRR) by multivariable-adjusted Poisson regression model. RESULTS: Meaningful
      decline in MGS presented in 24.3% of participants, especially in men (30.3%).
      Baseline knee pain level was significantly related to meaningful decline in MGS
      after adjustment of potential confounders (IRR 1.79 for mild pain, 1.84 for
      severe pain; P for trend <0.01). In sensitivity analyses with change in MGS as
      the continuous variable, the association was not significant, but a similar
      negative association with knee pain was confirmed (mild pain beta = -0.040,
      severe pain beta = -0.088; P for trend = 0.104). In addition, older adults with
      knee pain at both baseline and follow up had a higher risk of meaningful decline
      in MGS (IRR 2.33, 95% CI 1.59-3.40) compared with those who had no pain at
      baseline or follow up. CONCLUSIONS: Knee pain was associated with a decline in
      gait speed at 1-year follow up. Prevention and treatment of knee pain might be
      important for suppression of decline in physical function in older adults.

PMID- 25611951
TI  - Degradation in the fatigue strength of dentin by diamond bur preparations:
      Importance of cutting direction.
AB  - The objectives of this investigation were to evaluate the degradation in fatigue
      strength of dentin by diamond bur preparations and to identify the importance of
      cutting direction. Three groups of coronal dentin specimens were prepared from
      unrestored third molars, including a flaw free "control," and two groups that
      received a diamond bur cutting treatment performed parallel or perpendicular to
      the specimen length. The specimens were subjected to static or cyclic flexural
      loading to failure and the results were compared with data for carbide bur
      cutting. Under static loading diamond bur cutting resulted in significantly lower
      flexure strength (p <= 0.05) than the control for both cutting directions (from
      154 to ~124 MPa). However, there was no significant difference in the strength
      between the control and carbide bur treated specimens. Similarly, the fatigue
      strength of the diamond bur treated specimens was significantly lower (p <=
      0.0001) than that of the control for both cutting directions. Cutting in the
      perpendicular direction resulted in nearly 60% reduction to the endurance limit
      (from 44 to 19 MPa). Based on the results, diamond bur cutting of cavity
      preparations causes a reduction in the fatigue strength of dentin, regardless of
      the cutting direction. To maintain the durability of dentin, cavity preparations
      introduced using diamond burs must be performed with appropriate cutting
      direction and followed by a finishing pass.

PMID- 25611953
TI  - Correction.

PMID- 25611952
TI  - Potential for long-term transfer of dissolved organic carbon from riparian zones
      to streams in boreal catchments.
AB  - Boreal regions store most of the global terrestrial carbon, which can be
      transferred as dissolved organic carbon (DOC) to inland waters with implications
      for both aquatic ecology and carbon budgets. Headwater riparian zones (RZ) are
      important sources of DOC, and often just a narrow 'dominant source layer' (DSL)
      within the riparian profile is responsible for most of the DOC export. Two
      important questions arise: how long boreal RZ could sustain lateral DOC fluxes as
      the sole source of exported carbon and how its hydromorphological variability
      influences this role. We estimate theoretical turnover times by comparing carbon
      pools and lateral exports in the DSL of 13 riparian profiles distributed over a
      69 km(2) catchment in northern Sweden. The thickness of the DSL was 36 +/- 18
      (average +/- SD) cm. Thus, only about one-third of the 1-m-deep riparian profile
      contributed 90% of the lateral DOC flux. The 13 RZ exported 8.7 +/- 6.5 g C m(-2)
      year(-1) , covering the whole range of boreal stream DOC exports. The variation
      could be explained by local hydromorphological characteristics including RZ width
      (R(2) = 0.90). The estimated theoretical turnover times were hundreds to a few
      thousands of years, that is there is a potential long-lasting supply of DOC.
      Estimates of net ecosystem production in the RZ suggest that lateral fluxes,
      including both organic and inorganic C, could be maintained without drawing down
      the riparian pools. This was supported by measurements of stream DO(14) C that
      indicated modern carbon as the predominant fraction exported, including streams
      disturbed by ditching. The transfer of DOC into boreal inland waters from new and
      old carbon sources has a major influence on surface water quality and global
      carbon balances. This study highlights the importance of local variations in RZ
      hydromorphology and DSL extent for future DOC fluxes under a changing climate.

PMID- 25611954
TI  - Inhibition of c-Jun N-terminal kinase activation reverses Alzheimer disease
      phenotypes in APPswe/PS1dE9 mice.
AB  - OBJECTIVE: Growing evidence indicates that the activation of c-Jun N-terminal
      kinase (JNK) is implicated in the multiple major pathological features of
      Alzheimer disease (AD). However, whether specific inhibition of JNK activation
      could prevent disease progression in adult transgenic AD models at moderate stage
      remains unknown. Here we first investigated the potential disease-modifying
      therapeutic effect of systemic administration of SP600125, a small-molecule JNK
      specific inhibitor, in middle-aged APPswe/PS1dE9 mice. METHODS: Using behavioral,
      histological, and biochemical methods, outcomes of SP600125 treatment on
      neuropathology and cognitive deficits were studied in APPswe/PS1dE9 mice.
      RESULTS: Compared with vehicle-treated APPswe/PS1dE9 mice, chronic treatment of
      SP600125 for 12 weeks potently inhibited JNK activation, which resulted in a
      marked improvement of behavioral measures of cognitive deficits and a dramatic
      reduction in amyloid plaque burden, beta-amyloid production, tau
      hyperphosphorylation, inflammatory responses, and synaptic loss in these
      transgenic animals. In particular, we found that SP600125 treatment strongly
      promoted nonamyloidogenic amyloid precursor protein (APP) processing and
      inhibited amyloidogenic APP processing via regulating APP-cleavage secretase
      expression (ie, ADAM10, BACE1, and PS1) in APPswe/PS1dE9 mice. INTERPRETATION:
      Our findings demonstrate that chronic SP600125 treatment is powerfully effective
      in slowing down disease progression by markedly reducing multiple pathological
      features and ameliorating cognitive deficits associated with AD. This study
      highlights the concept that active JNK actually contributes to the development of
      the disease, and provides critical preclinical evidence that specific inhibition
      of JNK activation by SP600125 treatment may be a novel promising disease
      modifying therapeutic strategy for the treatment of AD.

PMID- 25611956
TI  - Perioperative management of alcohol withdrawal in an achondroplastic dwarf with
      an unstable cervical spine: a difficult management dilemma.
AB  - Patients presenting with alcohol withdrawal syndrome have an increased risk of
      perioperative events related to hemodynamic and respiratory instability. We
      present the case of a 49-year-old achondroplastic dwarf in alcohol withdrawal
      with cervical spinal cord injury and aortic dissection requiring emergency
      surgery. Due to conflicting perioperative management goals, a decision was made
      to delay surgery until the patient became clinically stable. Additional options
      might have been explored and resulted in better outcome. 

PMID- 25611955
TI  - Investigating Strength and Range of Motion of the Hip Complex in Ice Hockey
      Athletes.
AB  - CONTEXT: Ice hockey athletes frequently injure the hip complex via a noncontact
      mechanism. The authors investigated patterns of strength and range of motion
      (ROM) to establish major differences compared with soccer athletes. Soccer
      athletes were compared with ice hockey athletes due to similarities between the 2
      sports with regard to the intermittent nature and high number of lower-limb
      injuries. OBJECTIVE: To compare the differences in ROM and strength of the hip
      for both the dominant (Dom) and nondominant (Ndom) limbs in ice hockey and soccer
      athletes. DESIGN: Case-control study. SETTING: Bilateral ROM in hip flexion in
      sitting (FS) and lying (FL), extension, abduction, adduction, and internal
      rotation (IR) and external rotation (ER) were measured using a goniometer and
      assessed for strength using a handheld dynamometer on both the Dom and Ndom
      limbs. PARTICIPANTS: 24 male, active, uninjured NCAA Division III ice hockey (16)
      and soccer (8) athletes. MAIN OUTCOME MEASURES: ROM and strength for hip FS, FL,
      extension, abduction, adduction, IR, and ER. A mixed-model ANOVA was used to
      investigate interactions and main effects. RESULTS: Ice hockey athletes exhibited
      greater hip-adduction ROM than soccer athletes in the Dom leg (both P = .002) and
      when both limbs were combined (P = .010). Ice hockey athletes had less ROM in ER
      (P = .042) than soccer athletes. Ice hockey athletes displayed less strength in
      adduction in their Ndom leg than in their Dom leg (P = .02), along with less
      adduction than soccer players in their Ndom leg (P = .40). Ice hockey athletes
      displayed less strength in hip adduction (P = .030), FS (P = .023) and FL (P =
      .030) than soccer athletes. CONCLUSIONS: The findings suggest that ice hockey
      athletes may present an at-risk profile for noncontact hip injuries in comparison
      with soccer athletes with regard to strength and ROM of the hip.

PMID- 25611957
TI  - Editorial comments on perioperative management of alcohol withdrawal in
      achondroplastic dwarf with an unstable cervical spine: a difficult management
      dilemma.

PMID- 25611958
TI  - B-type natriuretic Peptide: not just a heart throb.
AB  - We present 2 cases of patients with septic shock and discuss changes in B-type
      natriuretic peptide (BNP) levels. While previous increases in BNP in septic shock
      were attributed to the accompanying myocardial depression, recent work claims
      that high levels of BNP in sepsis are related to an alteration in the BNP
      clearance pathway. We postulate from these cases that increased BNP should not
      automatically be associated with cardiac dysfunction and may assist in an early,
      difficult diagnosis of septic shock. 

PMID- 25611959
TI  - Severe hypotension related to high negative pressure suction drainage on a
      thoracic epidural drain during multilevel spinal fixation.
AB  - Hypotension or bradycardia or both related to intracranial hypotension after
      craniotomy has been reported in the literature. However, such reports are
      uncommon with thoracic epidural drains. We describe a case in which application
      of high negative pressure suction to a thoracic epidural drain caused a sudden
      decrease in arterial blood pressure. 

PMID- 25611960
TI  - Acute aortic occlusion presenting as paraplegia: a catastrophic complication in
      an elective surgical patient.
AB  - Acute aortic occlusion by massive thoracoabdominal thrombi has been reported as a
      serious complication in patients undergoing major vascular or cardiac surgical
      procedures. However, this complication occurs rarely after ambulatory procedures.
      In this case report, we describe a patient who experienced paraplegia after an
      elective laparoscopic cholecystectomy in whom acute aortic thromboembolic
      occlusion was subsequently diagnosed. We emphasize the importance of accurate
      neurologic and cardiovascular history taking and examination throughout the
      perioperative period along with the appropriate diagnostic studies to
      expeditiously arrive at a diagnosis of such a rare complication. 

PMID- 25611961
TI  - The use of beta-blockers is associated with the occurrence of acute kidney injury
      in severe alcoholic hepatitis.
AB  - BACKGROUND & AIMS: The beneficial effect of nonselective beta-blockers (NSBB) has
      recently been questioned in patients with end-stage cirrhosis. We analysed the
      impact of NSBB on outcomes in severe alcoholic hepatitis (AH). METHODS: This
      study was based on a prospective database of patients with severe, biopsy-proven
      AH. Patients admitted from July, 2006 to July, 2014 were retrospectively studied.
      Patients were divided into two groups (with and without NSBB) and assessed for
      the occurrence of Acute Kidney Injury (AKI) and transplant-free mortality during
      a 168-day follow-up period. RESULTS: One hundred thirty-nine patients were
      included, the mean Maddrey score was 71 +/- 34 and 86 patients (61.9%) developed
      AKI. Forty-eight patients (34.5%) received NSBB. The overall 168-day transplant
      free mortality was 50.5% (95%CI, 41.3-60.0%). The overall 168-day cumulative
      incidence of AKI was 61.9% (95%CI, 53.2-69.4%). When compared, patients with NSBB
      had a lower heart rate (65 +/- 13 vs 92 +/- 12, P < 0.0001) and a lower mean
      arterial pressure (MAP, 78 +/- 3 vs 87 +/- 5, P < 0.0001). Patients with NSBB had
      comparable MELD scores, Maddrey scores, and medical histories. The 168-day
      transplant-free mortality was 56.8% (95%CI, 41.3-69.7%) in patients with NSBB and
      46.7% (95%CI, 35.0-57.6%) without NSBB (P = 0.25). The 168-day cumulative
      incidence of AKI was 89.6% (95%CI, 74.9-95.9%) with NSBB compared to 50.4%
      (95%CI: 39.0-60.7) for no NSBB (P = 0.0001). The independent factors predicting
      AKI were a higher MELD score and the presence of NSBB. CONCLUSIONS: The use of
      NSBB in patients with severe AH is independently associated with a higher
      cumulative incidence of AKI.

PMID- 25611962
TI  - Oral Tadalafil in Children with Pulmonary Arterial Hypertension.
AB  - OBJECTIVE: Tadalafil is a selective Phosphodiesterase-5 inhibitor that has been
      reported to have vasodilatory and antiproliferative effects on the pulmonary
      artery. In this study we evaluated the safety and efficacy of oral tadalafil in
      children with pulmonary arterial hypertension (PAH). METHODS: This open label
      study, prospective and interventional was carried out in 25 known patients aged 2
      month-5 years in 3 medical centers in Iran, between March 2013-Jun 2014.
      Tadalafil suspension was administrated at 1 mg/kg daily for all patients.
      Hemodynamic and safety parameters were assessed at baseline and then monthly for
      a total of 4 visits. RESULTS: 19 patients received tadalafil as initial therapy,
      in all visits significant improvements in mean pulmonary arterial pressure were
      observed (p<0.01). Of the 25 patients, 6 (24%) had been on sildenafil for longer
      than 6 months. After transition from sildenafil to tadalafil clinical improvement
      was noted (p<0.05). Administration of tadalafil suspension was generally safe and
      well tolerated. Nausea was the most frequently reported adverse events which
      occurred in 3 patients during treatment. CONCLUSIONS: Oral tadalafil was
      administered easily and tolerated well and improved mean pulmonary artery
      pressure (MPAP) in children with PAH, which suggests that oral tadalafil may be
      more effective and safer than sildenafil in the treatment of PAH.

PMID- 25611968
TI  - Glyoxal Oxidation Mechanism: Implications for the Reactions HCO + O2 and OCHCHO +
      HO2.
AB  - A detailed mechanism for the thermal decomposition and oxidation of the flame
      intermediate glyoxal (OCHCHO) has been assembled from available theoretical and
      experimental literature data. The modeling capabilities of this extensive
      mechanism have been tested by simulating experimental HCO profiles measured at
      intermediate and high temperatures in previous glyoxal photolysis and pyrolysis
      studies. Additionally, new experiments on glyoxal pyrolysis and oxidation have
      been performed with glyoxal and glyoxal/oxygen mixtures in Ar behind shock waves
      at temperatures of 1285-1760 K at two different total density ranges. HCO
      concentration-time profiles have been detected by frequency modulation
      spectroscopy at a wavelength of lambda = 614.752 nm. The temperature range of
      available direct rate constant data of the high-temperature key reaction HCO + O2
      -> CO + HO2 has been extended up to 1705 K and confirms a temperature dependence
      consistent with a dominating direct abstraction channel. Taking into account
      available literature data obtained at lower temperatures, the following rate
      constant expression is recommended over the temperature range 295 K < T < 1705 K:
      k1/(cm(3) mol(-1) s(-1)) = 6.92 * 10(6) * T(1.90) * exp(+5.73 kJ/mol/RT). At
      intermediate temperatures, the reaction OCHCHO + HO2 becomes more important. A
      detailed reanalysis of previous experimental data as well as more recent
      theoretical predictions favor the formation of a recombination product in
      contrast to the formerly assumed dominating and fast OH-forming channel. Modeling
      results of the present study support the formation of HOCH(OO)CHO and provide a 2
      orders of magnitude lower rate constant estimate for the OH channel. Hence, low
      temperature generation of chain carriers has to be attributed to secondary
      reactions of HOCH(OO)CHO. 

PMID- 25611963
TI  - DNA motion induced by electrokinetic flow near an Au coated nanopore surface as
      voltage controlled gate.
AB  - We used fluorescence microscopy to investigate the diffusion and drift motion of
      lambda DNA molecules on an Au-coated membrane surface near nanopores, prior to
      their translocation through solid-state nanopores. With the capability of
      controlling electric potential at the Au surface as a gate voltage, Vgate, the
      motions of DNA molecules, which are presumably generated by electrokinetic flow,
      vary dramatically near the nanopores in our observations. We carefully
      investigate these DNA motions with different values of Vgate in order to alter
      the densities and polarities of the counterions, which are expected to change the
      flow speed or direction, respectively. Depending on Vgate, our observations have
      revealed the critical distance from a nanopore for DNA molecules to be attracted
      or repelled-DNA's anisotropic and unsteady drifting motions and accumulations of
      DNA molecules near the nanopore entrance. Further finite element method (FEM)
      numerical simulations indicate that the electrokinetic flow could qualitatively
      explain these unusual DNA motions near metal-collated gated nanopores. Finally,
      we demonstrate the possibility of controlling the speed and direction of DNA
      motion near or through a nanopore, as in the case of recapturing a single DNA
      molecule multiple times with alternating current voltages on the Vgate. 

PMID- 25611969
TI  - Clinical vestibular testing assessed with machine-learning algorithms.
AB  - IMPORTANCE: Dizziness and imbalance are common clinical problems, and accurate
      diagnosis depends on determining whether damage is localized to the peripheral
      vestibular system. Vestibular testing guides this determination, but the accuracy
      of the different tests is not known. OBJECTIVE: To determine how well each
      element of the vestibular test battery segregates patients with normal peripheral
      vestibular function from those with unilateral reductions in vestibular function.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of vestibular test
      batteries in 8080 patients. Clinical medical records were reviewed for a subset
      of individuals with the reviewers blinded to the vestibular test data.
      INTERVENTIONS: A group of machine-learning classifiers were trained using
      vestibular test data from persons who were "manually" labeled as having normal
      vestibular function or unilateral vestibular damage based on a review of their
      medical records. The optimal trained classifier was then used to categorize
      patients whose diagnoses were unknown, allowing us to determine the information
      content of each element of the vestibular test battery. MAIN OUTCOMES AND
      MEASURES: The information provided by each element of the vestibular test battery
      to segregate individuals with normal vestibular function from those with
      unilateral vestibular damage. RESULTS: The time constant calculated from the
      rotational test ranked first in information content, and measures that were
      related physiologically to the rotational time constant were 10 of the top 12
      highest-ranked variables. The caloric canal paresis ranked eighth, and the other
      elements of the test battery provided minimal additional information. The
      sensitivity of the rotational time constant was 77.2%, and the sensitivity of the
      caloric canal paresis was 59.6%; the specificity of the rotational time constant
      was 89.0%, and the specificity of the caloric canal paresis was 64.9%. The
      diagnostic accuracy of the vestibular test battery increased from 72.4% to 93.4%
      when the data were analyzed with the optimal machine-learning classifier.
      CONCLUSIONS AND RELEVANCE: Rotational testing should be considered the primary
      test to diagnose unilateral peripheral vestibular damage in patients with
      dizziness or imbalance. Most physicians, however, continue to rely on caloric
      tests to guide their diagnoses. Our results support a significant shift in the
      approach used to determine diagnoses in patients with vestibular symptoms.

PMID- 25611970
TI  - Peracetic acid oxidation of saline waters in the absence and presence of H 2O 2:
      secondary oxidant and disinfection byproduct formation.
AB  - Peracetic acid (PAA) is a disinfectant considered for use in ballast water
      treatment, but its chemical behavior in such systems (i.e., saline waters) is
      largely unknown. In this study, the reactivity of PAA with halide ions (chloride
      and bromide) to form secondary oxidants (HOCl, HOBr) was investigated. For the
      PAA-chloride and PAA-bromide reactions, second-order rate constants of (1.47 +/-
      0.58) * 10(-5) and 0.24 +/- 0.02 M(-1) s(-1) were determined for the formation of
      HOCl or HOBr, respectively. Hydrogen peroxide (H2O2), which is always present in
      PAA solutions, reduced HOCl or HOBr to chloride or bromide, respectively. As a
      consequence, in PAA-treated solutions with [H2O2] > [PAA], the HOBr (HOCl) steady
      state concentrations were low with a limited formation of brominated
      (chlorinated) disinfection byproducts (DBPs). HOI (formed from the PAA-iodide
      reaction) affected this process because it can react with H2O2 back to iodide.
      H2O2 is thus consumed in a catalytic cycle and leads to less efficient HOBr
      scavenging at even low iodide concentrations (<1 MUM). In PAA-treated solutions
      with [H2O2] < [PAA] and high bromide levels, mostly brominated DBPs are formed.
      In synthetic water, bromate was formed from the oxidation of bromide. In natural
      brackish waters, bromoform (CHBr3), bromoacetic acid (MBAA), dibromoacetic acid
      (DBAA), and tribromoacetic acid (TBAA) formed at up to 260, 106, 230, and 89
      MUg/L, respectively for doses of 2 mM (ca. 150 mg/L) PAA and [H2O2] < [PAA]. The
      same brackish waters, treated with PAA with [H2O2] ? [PAA], similar to conditions
      found in commercial PAA solutions, resulted in no trihalomethanes and only low
      haloacetic acid concentrations.

PMID- 25611971
TI  - Delimiting areas of endemism through kernel interpolation.
AB  - We propose a new approach for identification of areas of endemism, the
      Geographical Interpolation of Endemism (GIE), based on kernel spatial
      interpolation. This method differs from others in being independent of grid
      cells. This new approach is based on estimating the overlap between the
      distribution of species through a kernel interpolation of centroids of species
      distribution and areas of influence defined from the distance between the
      centroid and the farthest point of occurrence of each species. We used this
      method to delimit areas of endemism of spiders from Brazil. To assess the
      effectiveness of GIE, we analyzed the same data using Parsimony Analysis of
      Endemism and NDM and compared the areas identified through each method. The
      analyses using GIE identified 101 areas of endemism of spiders in Brazil GIE
      demonstrated to be effective in identifying areas of endemism in multiple scales,
      with fuzzy edges and supported by more synendemic species than in the other
      methods. The areas of endemism identified with GIE were generally congruent with
      those identified for other taxonomic groups, suggesting that common processes can
      be responsible for the origin and maintenance of these biogeographic units. 

PMID- 25611972
TI  - Genetic features of metachronous esophageal cancer developed in Hodgkin's
      lymphoma or breast cancer long-term survivors: an exploratory study.
AB  - BACKGROUND: Development of novel therapeutic drugs and regimens for cancer
      treatment has led to improvements in patient long-term survival. This success
      has, however, been accompanied by the increased occurrence of second primary
      cancers. Indeed, patients who received regional radiotherapy for Hodgkin's
      Lymphoma (HL) or breast cancer may develop, many years later, a solid
      metachronous tumor in the irradiated field. Despite extensive epidemiological
      studies, little information is available on the genetic changes involved in the
      pathogenesis of these solid therapy-related neoplasms. METHODS: Using
      microsatellite markers located in 7 chromosomal regions frequently deleted in
      sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and
      microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty
      samples were of esophageal carcinoma developed in HL or breast cancer long-term
      survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while
      26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11
      EADC). RESULTS: We found that, though the overall LOH frequency at the studied
      chromosomal regions was similar among metachronous and sporadic tumors, the
      latter exhibited a statistically different higher LOH frequency at 17q21.31 (p =
      0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2
      and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of
      the genetic determinants located nearby these regions in the development of the
      two esophageal cancer histotypes. CONCLUSIONS: Altogether, our results strengthen
      the genetic diversity among ESCC and EADC whether they occurred spontaneously or
      after therapeutic treatments. The presence of histotype-specific alterations in
      esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests
      that their transformation process, though the putative different etiological
      origin, may retrace sporadic ESCC and EADC carcinogenesis.

PMID- 25611973
TI  - Sleep duration, schedule and quality among urban Chinese children and
      adolescents: associations with routine after-school activities.
AB  - BACKGROUND: With rapid urbanization accompanied by lifestyle changes, children
      and adolescents living in metropolitan areas are faced with many time use choices
      that compete with sleep. This study reports on the sleep hygiene of urban Chinese
      school students, and investigates the relationship between habitual after-school
      activities and sleep duration, schedule and quality on a regular school day.
      METHODS: Cross-sectional, school-based survey of school children (Grades 4-8)
      living in Shanghai, China, conducted in 2011. Self-reported data were collected
      on students' sleep duration and timing, sleep quality, habitual after-school
      activities (i.e. homework, leisure-time physical activity, recreational screen
      time and school commuting time), and potential correlates. RESULTS: Mean sleep
      duration of this sample (mean age: 11.5-years; 48.6% girls) was 9 hours. Nearly
      30% of students reported daytime tiredness. On school nights, girls slept less
      (p<0.001) and went to bed later (p<0.001), a sex difference that was more
      pronounced in older students. Age by sex interactions were observed for both
      sleep duration (p=0.005) and bedtime (p=0.002). Prolonged time spent on homework
      and mobile phone playing was related to shorter sleep duration and later bedtime.
      Adjusting for all other factors, with each additional hour of mobile phone
      playing, the odds of daytime tiredness and having difficulty maintaining sleep
      increased by 30% and 27% among secondary students, respectively. CONCLUSION:
      There are sex differences in sleep duration, schedule and quality. Habitual
      activities had small but significant associations with sleep hygiene outcomes
      especially among secondary school students. Intervention strategies such as
      limiting children's use of electronic screen devices after school are implicated.

PMID- 25611975
TI  - Directing group assisted nucleophilic substitution of propargylic alcohols via o
      quinone methide intermediates: Bronsted acid catalyzed, highly enantio- and
      diastereoselective synthesis of 7-alkynyl-12a-acetamido-substituted
      benzoxanthenes.
AB  - BINOL-based, chiral phosphoric acids catalyze the substitution of 1-(o
      hydroxyphenyl)propargylic alcohols with enamides to furnish 7-alkynyl-12a
      acetamido-substituted benzo[c]xanthenes and related heterocycles in a one-pot
      operation with excellent diastereo- and enantioselectivity. Ambient reaction
      temperature, operationally simple reaction conditions, low catalyst loading, high
      yields, and excellent stereocontrol are attractive features of this process and
      make it a highly practical and versatile transformation. 

PMID- 25611974
TI  - Thymoquinone induces caspase-independent, autophagic cell death in CPT-11
      resistant lovo colon cancer via mitochondrial dysfunction and activation of JNK
      and p38.
AB  - Chemotherapy causes unwanted side effects and chemoresistance, limiting its
      effectiveness. Therefore, phytochemicals are now used as alternative treatments.
      Thymoquinone (TQ) is used to treat different cancers, including colon cancer. The
      irinotecan-resistant (CPT-11-R) LoVo colon cancer cell line was previously
      constructed by stepwise CPT-11 challenges to untreated parental LoVo cells. TQ
      dose-dependently increased the total cell death index and activated apoptosis at
      2 MUM, which then diminished at increasing doses. The possibility of autophagic
      cell death was then investigated. TQ caused mitochondrial outer membrane
      permeability (MOMP) and activated autophagic cell death. JNK and p38 inhibitors
      (SP600125 and SB203580, respectively) reversed TQ autophagic cell death. TQ was
      also found to activate apoptosis before autophagy, and the direction of cell
      death was switched toward autophagic cell death at initiation of autophagosome
      formation. Therefore, TQ resulted in caspase-independent, autophagic cell death
      via MOMP and activation of JNK and p38 in CPT-11-R LoVo colon cancer cells.

PMID- 25611976
TI  - Real-time measurement of the vertical binding energy during the birth of a
      solvated electron.
AB  - Using femtosecond time-resolved two-photon photoelectron spectroscopy, we
      determine (i) the vertical binding energy (VBE = 0.8 eV) of electrons in the
      conduction band in supported amorphous solid water (ASW) layers, (ii) the time
      scale of ultrafast trapping at pre-existing sites (22 fs), and (iii) the initial
      VBE (1.4 eV) of solvated electrons before significant molecular reorganization
      sets in. Our results suggest that the excess electron dynamics prior to solvation
      are representative for bulk ASW. 

PMID- 25611977
TI  - Efficient chemisorption of organophosphorous redox probes on indium tin oxide
      surfaces under mild conditions.
AB  - We report a mild and straightforward one-step chemical surface functionalization
      of indium tin oxide (ITO) electrodes by redox-active molecules bearing an
      organophosphoryl anchoring group (i.e., alkyl phosphate or alkyl phosphonate
      group). The method takes advantage of simple passive adsorption in an aqueous
      solution at room temperature. We show that organophosphorus compounds can adsorb
      much more strongly and stably on an ITO surface than analogous redox-active
      molecules bearing a carboxylate or a boronate moiety. We provide evidence,
      through quantitative electrochemical characterization (i.e., by cyclic
      voltammetry) of the adsorbed organophosphoryl redox-active molecules, of the
      occurrence of three different adsorbate fractions on ITO, exhibiting different
      stabilities on the surface. Among these three fractions, one is observed to be
      strongly chemisorbed, exhibiting high stability and resistance to
      desorption/hydrolysis in a free-redox probe aqueous buffer. We attribute this
      remarkable stability to the formation of chemical bonds between the
      organophosphorus anchoring group and the metal oxide surface, likely occurring
      through a heterocondensation reaction in water. From XPS analysis, we also
      demonstrate that the surface coverage of the chemisorbed molecules is highly
      affected by the degree of surface hydroxylation, a parameter that can be tuned by
      simply preconditioning the freshly cleaned ITO surfaces in water. The lower the
      relative surface hydroxide density on ITO, the higher was the surface coverage of
      the chemisorbed species. This behavior is in line with a chemisorption mechanism
      involving coordination of a deprotonated phosphoryl oxygen atom to the non
      hydroxylated acidic metal sites of ITO. 

PMID- 25611978
TI  - HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently
      associated with histological features of NASH in HCV-infected patients.
AB  - Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver
      disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in
      genotype 3, but its clinical significance is debated. As squamous cell carcinoma
      antigen (SCCA)-IgM has been associated with advanced liver disease and risk of
      tumour development, we evaluated its occurrence in CHC and the possible relation
      with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured
      in 91 patients with CHC at the time of liver biopsy performed before antiviral
      treatment, at the end of treatment and 6 months thereafter, and in 93 HCV
      negative patients with histological diagnosis of nonalcoholic fatty liver
      disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of
      controls. This biomarker was found more elevated in CHC patients with
      histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were
      independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44
      166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and
      a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were
      80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with
      sustained virologic response to therapy, SCCA-IgM levels decreased significantly,
      while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is
      detectable in one-third of patients with CHC and significantly correlates with
      histological NASH.

PMID- 25611979
TI  - Effects of tissue water content on the propagation of laser light during low
      level laser therapy.
AB  - This work reports that the laser fluence rate inside porcine skin varied notably
      with the change of tissue water content under the same laser irradiation
      conditions. The laser fluence rate inside skin tissue samples with varying water
      content was measured using an optical fiber sensor, while the target was
      irradiated either by a low-level 635 or 830 nm laser (50 mW/cm2). It was
      demonstrated that the distribution of laser fluence rate inside the target is
      strongly affected by tissue water content and its profile is determined by the
      water content dependency of optical properties at the laser wavelength.

PMID- 25611980
TI  - Measuring the dynamics of cyclic adenosine monophosphate level in living cells
      induced by low-level laser irradiation using bioluminescence resonance energy
      transfer.
AB  - Several studies demonstrated that the cyclic adenosine monophosphate (cAMP), an
      important second messenger, is involved in the mechanism of low-level laser
      irradiation (LLLI) treatment. However, most of these studies obtained the cAMP
      level in cell culture extracts or supernatant. In this study, the cAMP level in
      living cells was measured with bioluminescence resonance energy transfer (BRET).
      The effect of LLLI on cAMP level in living cells with adenosine receptors blocked
      was explored to identify the role of adenosine receptors in LLLI. The results
      showed that LLLI increased the cAMP level. Moreover, the rise of cAMP level was
      light dose dependent but wavelength independent for 658-, 785-, and 830-nm laser
      light. The results also exhibited that the adenosine receptors, a class of G
      protein-coupled receptor (GPCR), modulated the increase of cAMP level induced by
      LLLI. The cAMP level increased more significantly when the A3 adenosine receptors
      (A3R) were blocked by A3R antagonist compared with A1 adenosine receptor or A2a
      adenosine receptor blocked in HEK293T cells after LLLI, which was in good
      agreement with the adenosine receptors' expressions. All these results suggested
      that measuring the cAMP level with BRET could be a useful technique to study the
      role of GPCRs in living cells under LLLI.

PMID- 25611982
TI  - Misplacement of a pulmonary artery catheter.
AB  - Placing a flow-directed pulmonary artery catheter (PAC) can be difficult and lead
      to serious complications. We present the case of an attempted PAC insertion in a
      patient undergoing implantation of a left ventricular assist device. Although
      physiologic pressure waveforms were established, plausible measurements of
      cardiac output and pulmonary capillary wedge pressure were not initially
      obtainable. Chest radiography showed that the catheter was looped in the
      pulmonary artery. This malposition could not be visualized intraoperatively by
      transesophageal echocardiography. The PAC was replaced in the operating room
      after the left ventricular assist device was implanted. 

PMID- 25611981
TI  - Integrative analysis of genomics and proteomics data on clinical breast cancer
      tissue specimens extracted with acid guanidinium thiocyanate-phenol-chloroform.
AB  - Acid guanidinium thiocyanate, phenol, and chloroform extraction (AGPC) is a
      commonly used procedure to extract RNA from fresh frozen tissues and cell lines.
      In addition, DNA and proteins can be recovered, which makes AGPC an attractive
      source for integrative analysis on tissues of which little material is available,
      such as clinical specimens. Despite this potential, AGPC has only scarcely been
      used for proteomic analysis, mainly due to difficulties in extracting proteins.
      We have used a quantitative mass spectrometry method to show that proteins can
      readily be recovered from AGPC extracted tissues with high recovery and
      repeatability, which allows this method to be used for global proteomic
      profiling. Protein expression data for a selected number of clinically relevant
      markers, of which transcript and protein levels are known to be correlated, were
      in agreement with genomic and transcriptomic data obtained from the same AGPC
      lysate. Furthermore, global proteomic profiling successfully discriminated breast
      tumor tissues according to their clinical subtype. Lastly, a reference gene set
      of differentially expressed transcripts was strongly enriched in the
      differentially abundant proteins in our cohort. AGPC lysates are therefore well
      suited for comparative protein and integrative analyses. 

PMID- 25611983
TI  - Identification and management of a coronary sinus catheter fracture.
AB  - At facilities that offer cardiac surgery services, minimally invasive
      cardiothoracic surgery is fast becoming commonplace, particularly in aortic,
      tricuspid, and mitral valve procedures. Use of a coronary sinus catheter, a
      specialized central venous catheter, to monitor hypothermic depth and provide
      retrograde cardioplegia has been widely adopted at Tufts Medical Center.
      Complications of coronary sinus catheter insertion are considered rare but are
      well documented. In contrast, complications of catheter removal, such as the
      catheter fracture that we report here, are not well described in the literature.
      In this case, the catheter tip was retrieved without further patient harm or
      additional invasive interventions. 

PMID- 25611985
TI  - Editorial comment: misadventures with central venous catheters.

PMID- 25611984
TI  - A significant complication that occurred during insertion of dual guidewires into
      the right internal jugular vein for central venous catheterization.
AB  - We report a significant complication that occurred during double guidewire
      insertion. The first guidewire (GW1) was inserted under ultrasonographic
      guidance, whereas the second guidewire (GW2) was inserted by the landmark-based
      method. Subsequently, GW2 penetrated and entangled with GW1, which caused
      difficulty in removing both guidewires. A dilator was used to dilate the puncture
      site, allowing simultaneous removal of both guidewires with minimal invasion. The
      first guidewire was found to be pointing in a cranial direction, indicating the
      manner in which the second guidewire's puncture needle had penetrated it. Thus,
      when double cannulation is performed, guidewire position should be confirmed. 

PMID- 25611986
TI  - Conversion of hemiblock to complete heart block by intraoperative motor-evoked
      potential monitoring.
AB  - Intraoperative monitoring of nervous system pathways, including assessing the
      integrity of descending motor pathways with motor-evoked potentials, is often
      performed in intracranial and spine operations to reduce the risk of iatrogenic
      neurological impairment. We present a case in which intraoperative monitoring
      with motor-evoked potentials resulted in complete heart block in a patient with a
      history of hemiblock. Neuromonitoring has been associated with arrhythmias in
      patients with ostensibly normal conduction systems, and we propose that
      monitoring personnel, anesthesiologists, and surgeons need to be aware of this
      risk and exercise caution when monitoring motor-evoked potentials in patients
      with known conduction deficits. 

PMID- 25611987
TI  - A multiscale quantum mechanics/electromagnetics method for device simulations.
AB  - Multiscale modeling has become a popular tool for research applying to different
      areas including materials science, microelectronics, biology, chemistry, etc. In
      this tutorial review, we describe a newly developed multiscale computational
      method, incorporating quantum mechanics into electronic device modeling with the
      electromagnetic environment included through classical electrodynamics. In the
      quantum mechanics/electromagnetics (QM/EM) method, the regions of the system
      where active electron scattering processes take place are treated quantum
      mechanically, while the surroundings are described by Maxwell's equations and a
      semiclassical drift-diffusion model. The QM model and the EM model are solved,
      respectively, in different regions of the system in a self-consistent manner.
      Potential distributions and current densities at the interface between QM and EM
      regions are employed as the boundary conditions for the quantum mechanical and
      electromagnetic simulations, respectively. The method is illustrated in the
      simulation of several realistic systems. In the case of junctionless field-effect
      transistors, transfer characteristics are obtained and a good agreement between
      experiments and simulations is achieved. Optical properties of a tandem
      photovoltaic cell are studied and the simulations demonstrate that multiple QM
      regions are coupled through the classical EM model. Finally, the study of a
      carbon nanotube-based molecular device shows the accuracy and efficiency of the
      QM/EM method. 

PMID- 25611988
TI  - Correction to "activation barriers in the growth of molecular clusters derived
      from sulfuric Acid and ammonia".

PMID- 25611989
TI  - Total synthesis of a thromboxane receptor antagonist, terutroban.
AB  - A total synthesis of terutroban is achieved using the Claisen rearrangement,
      Friedel-Crafts acylation and Heck coupling as key reactions, avoiding the
      classical Diels-Alder approach used before. 

PMID- 25611990
TI  - Spinal cord stimulator placement in a patient with complex regional pain syndrome
      and ankylosing spondylitis: a novel approach with dual benefits.
AB  - Spinal cord stimulation is a treatment modality used to treat various chronic
      pain conditions, including complex regional pain syndrome (CRPS). We present a
      case in which spinal cord stimulation was used for the treatment of lower
      extremity CRPS in a patient with ankylosing spondylitis. Preoperative imaging
      demonstrated fusion of the lumbothoracic spine with obliteration of the
      interlaminar spaces. The sacral hiatus remained open and was used to access the
      epidural space, facilitating the placement of 2 thoracic epidural electrodes. The
      resulting stimulation controlled not only the patient's lower extremity CRPS pain
      but also alleviated his chronic axial pain secondary to ankylosing spondylitis. 

PMID- 25611991
TI  - Editorial comment: spinal cord stimulator placement in a patient with complex
      regional pain syndrome and ankylosing spondylitis: a novel approach with dual
      benefits.

PMID- 25611992
TI  - Esophageal perforation and pneumothorax after routine intraoperative orogastric
      tube placement.
AB  - Orogastric and nasogastric tubes are routinely inserted in anesthetized patients
      to both reduce the volume of stomach contents and decrease the incidence of
      postoperative nausea. We present a case of esophageal perforation and subsequent
      pneumothorax after insertion of an orogastric tube in a patient undergoing
      routine shoulder arthroscopy. 

PMID- 25611993
TI  - Editorial comment: esophageal perforation and pneumothorax after routine
      intraoperative orogastric tube placement.

PMID- 25611994
TI  - The use of veno-venous extracorporeal membrane oxygenation for perinatal support
      of an infant with d-transposition of the great arteries, intact atrial and
      ventricular septa, and flow-restricted ductus arteriosus.
AB  - Prenatal assessment of a fetus with D-transposition of the great arteries
      demonstrated an absence of mixing between systemic and pulmonary circulations,
      and predicted lethal postnatal hypoxemia. A multidisciplinary meeting evaluated
      therapeutic options. After cesarean delivery, veno-venous extracorporeal membrane
      oxygenation was instituted in preparation for open atrial septectomy. The infant
      subsequently underwent an arterial switch procedure. Prenatal delineation of
      pulmonary and systemic circulations in the fetus with D-transposition of the
      great arteries influences postnatal management. Multidisciplinary planning
      enhanced the perinatal outcome. 

PMID- 25611995
TI  - Editorial comment: the use of veno-venous extracorporeal membrane oxygenation for
      perinatal support of an infant with d-transposition of the great arteries, intact
      atrial and ventricular septa, and flow-restricted ductus arteriosus.

PMID- 25611996
TI  - Ultrasound-guided paravertebral block facilitated tracheal extubation in a 5-week
      old infant with rib fractures and respiratory failure.
AB  - The use of regional anesthesia including paravertebral blocks has been advocated
      for the treatment of pain from rib fractures in adults. Although paravertebral
      nerve blocks have been used in pediatric patients to manage postoperative pain
      for surgeries to the thorax and abdomen, their use for analgesia after rib
      fractures and thoracic trauma has not been reported. We report the use of a T7
      continuous paravertebral nerve block for pain relief in a 5-week-old, 5-kg infant
      who suffered T7 and T8 rib fractures and a pulmonary contusion to the left chest
      secondary to a gunshot wound. 

PMID- 25611997
TI  - Variable noninnocence of substituted azobis(phenylcyanamido)diruthenium
      complexes.
AB  - The synthetic chemistry of substituted 4,4'-azobis(phenylcyanamide) ligands was
      investigated, and the complexes [{Ru(tpy)(bpy)}2(MU-L)][PF6]2, where L =
      2,2':5,5'-tetramethyl-4,4'-azobis(phenylcyanamido) (Me4adpc(2-)), 2,2'-dimethyl
      4,4'-azobis(phenylcyanamido) (Me2adpc(2-)), unsubstituted (adpc(2-)), 3,3'
      dichloro-4,4'-azobis(phenylcyanamido) (Cl2adpc(2-)), and 2,2':5,5'-tetrachloro
      4,4'-azobis(phenylcyanamido) (Cl4adpc(2-)), were prepared and characterized by
      cyclic voltammetry and vis-near-IR (NIR) and IR spectroelectrochemistry. The room
      temperature electron paramagnetic resonance spectrum of [{Ru(tpy)(bpy)}2(MU
      Me4adpc)](3+) showed an organic radical signal and is consistent with an
      oxidation-state description [Ru(II), Me4adpc(*-), Ru(II)](3+), while that of
      [{Ru(tpy)(bpy)}2(MU-Cl2adpc)](3+) at 10 K showed a low-symmetry Ru(III) signal,
      which is consistent with the description [Ru(III), Cl2adpc(2-), Ru(II)](3+). IR
      spectroelectrochemistry data suggest that [{Ru(tpy)(bpy)}2(MU-adpc)](3+) is
      delocalized and [{Ru(tpy)(bpy)}2(MU-Cl2adpc)](3+) and [{Ru(tpy)(bpy)}2(MU
      Cl4adpc)](3+) are valence-trapped mixed-valence systems. A NIR absorption band
      that is unique to all [{Ru(tpy)(bpy)}2(MU-L)](3+) complexes is observed; however,
      its energy and intensity vary depending on the nature of the bridging ligand and,
      hence, the complexes' oxidation-state description. 

PMID- 25611998
TI  - Single nanowire manipulation within dielectrophoretic force fields in the sub
      crossover frequency regime.
AB  - This paper presents the quantitative relationship between the control parameters
      of a dielectrophoretic (DEP) force field and the resulting electrokinetic region
      of influence experienced by individual nanowires (NWs) in colloidal suspensions.
      Our results show that DEP operation at sub-crossover frequencies, which are
      defined as frequencies slightly below the transition from positive-to-negative
      DEP, offers a suitable but previously unexplored performance regime for single NW
      manipulation and assembly. The low-magnitude DEP forces at these frequencies,
      which are estimated to be 8 orders of magnitude smaller as compared to near-DC
      frequencies, provide an efficient avenue to controllably extend electrokinetic
      influence on suspension volumes that present isolated NWs. These results are
      demonstrated using alpha-phase manganese dioxide NWs as a model one-dimensional
      construct. Based on experimentally extracted values for the NW intrinsic
      conductivity and dielectric permittivity, we employ computational models to
      explain each of the performance regimes observed in this nanoassembly system. In
      addition, we use a new approach to estimate the concentration of a NW suspension
      from experimentally observed data for deposition yields. 

PMID- 25611999
TI  - Dramatic improvement of severe cryptococcosis-induced immune reconstitution
      syndrome with adalimumab in a renal transplant recipient.
AB  - In solid organ transplant recipients, immune reconstitution inflammatory syndrome
      (IRIS) is a rare complication of cryptococcosis, which may require steroids in
      its most severe forms. Here, we report the case of a renal transplant recipient
      who developed severe cryptococcal meningitis-associated IRIS 1 week after
      immunosuppression reduction. High-dose steroids failed to improve the disease.
      Finally, a recombinant human monoclonal tumor necrosis factor-alpha (TNF-alpha)
      antagonist, adalimumab, was prescribed, and the patient rapidly experienced
      dramatic neurological improvement. No IRIS relapse occurred within 14 months
      following adalimumab discontinuation.

PMID- 25612000
TI  - Occurrence of Giardia and Cryptosporidium in captive chimpanzees (Pan
      troglodytes), mandrills (Mandrillus sphinx) and wild Zanzibar red colobus monkeys
      (Procolobus kirkii).
AB  - BACKGROUND: The aim of this study was to investigate the occurrence of Giardia
      duodenalis and Cryptosporidium spp. in primates and determine their zoonotic or
      anthropozoonotic potential. METHODS: Direct immunofluorescence was used to
      identify Giardia and Cryptosporidium from faecal samples. PCR and DNA sequencing
      was performed on positive results. RESULTS: Giardia cysts were identified from
      5.5% (5/90) of captive chimpanzees and 0% (0/11) of captive mandrills in the
      Republic of Congo; 0% (0/10) of captive chimpanzees in Norway; and 0% of faecal
      samples (n = 49) from wild Zanzibar red colobus monkeys. Two Giardia positive
      samples were also positive on PCR, and sequencing revealed identical isolates of
      Assemblage B. Cryptosporidium oocysts were not detected in any of the samples.
      CONCLUSIONS: In these primate groups, in which interactions with humans and human
      environments are quite substantial, Giardia and Cryptosporidium are rare
      pathogens. In chimpanzees, Giardia may have a zoonotic or anthropozoonotic
      potential.

PMID- 25612001
TI  - Considerations for anesthesia staffing in a trauma center: new standards,
      education, and safety.
AB  - PURPOSE OF REVIEW: A review of recent updates to trauma anesthesia service
      requirements in the USA and UK, the evolving role of the trauma anesthesiologist,
      and opportunities for education and training. Considerations of cost and safety
      for staffing arrangements are discussed. RECENT FINDINGS: Certifying and
      specialty organizations have recently escalated the availability requirements and
      training recommendations for anesthesiology services in trauma centers. SUMMARY:
      There is a growing recognition that trauma anesthesiology represents a distinct
      area of subspecialty knowledge. Anesthesiology specialty organizations advocate
      for trauma-specific knowledge and training for trauma anesthesia providers.
      Requiring the in-house presence of anesthesia providers in level I and level II
      trauma centers may impose significant costs on medical centers that do not
      currently provide those services.

PMID- 25612002
TI  - Lipo-oxytocin-1, a Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups,
      Has Long-Lasting Effects on Anxiety-Related Behavior and Social Avoidance in
      CD157 Knockout Mice.
AB  - Oxytocin (OT) is a nonapeptide hormone that is secreted into the brain and blood
      circulation. OT has not only classical neurohormonal roles in uterine contraction
      and milk ejection during the reproductive phase in females, but has also been
      shown to have new pivotal neuromodulatory roles in social recognition and
      interaction in both genders. A single administration of OT through nasal spray
      increases mutual recognition and trust in healthy subjects and psychiatric
      patients, suggesting that OT is a potential therapeutic drug for autism spectrum
      disorders, schizophrenia, and some other psychiatric disorders. Although the
      mechanism is not well understood, it is likely that OT can be transported into
      the brain where it activates OT receptors to exert its function in the brain.
      However, the amount transported into the brain may be low. To ensure equivalent
      effects, an OT analog with long-lasting and effective blood-brain barrier
      penetration properties would be beneficial for use as a therapeutic drug. Here,
      we designed and synthesized a new oxytocin analog, lipo-oxytocin-1 (LOT-1), in
      which two palmitoyl groups are conjugated at the amino group of the cysteine9
      residue and the phenolic hydroxyl group of the tyrosine8 residue of the OT
      molecule. To determine whether LOT-1 actually has an effect on the central
      nervous system, we examined its effects in a CD157 knockout model mouse of the
      non-motor psychiatric symptoms of Parkinson's disease. Similar to OT, this analog
      rescued anxiety-like behavior and social avoidance in the open field test with
      the social target in a central arena 30 min after intraperitoneal injection in
      CD157 knockout mice. When examined 24 h after injection, the mice treated with
      LOT-1 displayed more recovery than those given OT. The results suggest that LOT-1
      has a functional advantage in recovery of social behavioral impairment, such as
      those caused by neurodegenerative diseases, autism spectrum disorders, and
      schizophrenia. 

PMID- 25612004
TI  - Arsenic Cycling in Hydrocarbon Plumes: Secondary Effects of Natural Attenuation.
AB  - Monitored natural attenuation is widely applied as a remediation strategy at
      hydrocarbon spill sites. Natural attenuation relies on biodegradation of
      hydrocarbons coupled with reduction of electron acceptors, including solid phase
      ferric iron (Fe(III)). Because arsenic (As) adsorbs to Fe-hydroxides, a potential
      secondary effect of natural attenuation of hydrocarbons coupled with Fe(III)
      reduction is a release of naturally occurring As to groundwater. At a crude-oil
      contaminated aquifer near Bemidji, Minnesota, anaerobic biodegradation of
      hydrocarbons coupled to Fe(III) reduction has been well documented. We collected
      groundwater samples at the site annually from 2009 to 2013 to examine if As is
      released to groundwater and, if so, to document relationships between As and Fe
      inside and outside of the dissolved hydrocarbon plume. Arsenic concentrations in
      groundwater in the plume reached 230 ug/L, whereas groundwater outside the plume
      contained less than 5 ug/L As. Combined with previous data from the Bemidji site,
      our results suggest that (1) naturally occurring As is associated with Fe
      hydroxides present in the glacially derived aquifer sediments; (2) introduction
      of hydrocarbons results in reduction of Fe-hydroxides, releasing As and Fe to
      groundwater; (3) at the leading edge of the plume, As and Fe are removed from
      groundwater and retained on sediments; and (4) downgradient from the plume,
      patterns of As and Fe in groundwater are similar to background. We develop a
      conceptual model of secondary As release due to natural attenuation of
      hydrocarbons that can be applied to other sites where an influx of biodegradable
      organic carbon promotes Fe(III) reduction. 

PMID- 25612003
TI  - Pathologic Regulation of Collagen I by an Aberrant Protein Phosphatase 2A/Histone
      Deacetylase C4/MicroRNA-29 Signal Axis in Idiopathic Pulmonary Fibrosis
      Fibroblasts.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by the relentless expansion
      of fibroblasts depositing type I collagen within the alveolar wall and
      obliterating the alveolar airspace. MicroRNA (miR)-29 is a potent regulator of
      collagen expression. In IPF, miR-29 levels are low, whereas type I collagen
      expression is high. However, the mechanism for suppression of miR-29 and
      increased type I collagen expression in IPF remains unclear. Here we show that
      when IPF fibroblasts are seeded on polymerized type I collagen, miR-29c levels
      are suppressed and type I collagen expression is high. In contrast, miR-29c is
      high and type I collagen expression is low in control fibroblasts. We demonstrate
      that the mechanism for suppression of miR-29 during IPF fibroblast interaction
      with polymerized collagen involves inappropriately low protein phosphatase (PP)
      2A function, leading to histone deacetylase (HDA) C4 phosphorylation and
      decreased nuclear translocation of HDAC4. We demonstrate that overexpression of
      HDAC4 in IPF fibroblasts restored miR-29c levels and decreased type I collagen
      expression, whereas knocking down HDAC4 in control fibroblasts suppressed miR-29c
      levels and increased type I collagen expression. Our data indicate that IPF
      fibroblast interaction with polymerized type I collagen results in an aberrant
      PP2A/HDAC4 axis, which suppresses miR-29, causing a pathologic increase in type I
      collagen expression. 

PMID- 25612005
TI  - Maternal lipid levels during pregnancy and gestational diabetes: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Lipid levels during pregnancy in women with gestational diabetes
      mellitus (GDM) have been extensively studied; however, it remains unclear whether
      dyslipidaemia is a potential marker of preexisting insulin resistance. OBJECTIVE:
      To evaluate the relationship between lipid measures throughout pregnancy and GDM.
      SEARCH STRATEGY: We searched PubMed-MedLine and SCOPUS (inception until January
      2014) and reference lists of relevant studies. SELECTION CRITERIA: Publications
      describing original data with at least one raw lipid (total cholesterol, high
      density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL
      C], or triglyceride) measurement during pregnancy in women with GDM and healthy
      pregnant controls were retained. DATA COLLECTION AND ANALYSIS: Data extracted
      from 60 studies were pooled and weighted mean difference (WMD) in lipid levels
      was calculated using random effects models. Meta-regression was also performed to
      identify sources of heterogeneity. MAIN RESULTS: Triglyceride levels were
      significantly elevated in women with GDM compared with those without GDM (WMD
      30.9, 95% confidence interval [95% CI] 25.4-36.4). This finding was consistent in
      the first, second and third trimesters of pregnancy. HDL-C levels were
      significantly lower in women with GDM compared with those without GDM in the
      second (WMD -4.6, 95% CI -6.2 to -3.1) and third (WMD -4.1, 95% CI -6.5 to -1.7)
      trimesters of pregnancy. There were no differences in aggregate total cholesterol
      or LDL-C levels between women with GDM and those without insulin resistance.
      AUTHOR'S CONCLUSIONS: Our meta-analysis shows that triglycerides are
      significantly elevated among women with GDM compared with women without insulin
      resistance and this finding persists across all three trimesters of pregnancy.

PMID- 25612006
TI  - A polyubiquitin chain reaction: parkin recruitment to damaged mitochondria.

PMID- 25612007
TI  - Clinical significance of the glucose breath test in patients with inflammatory
      bowel disease.
AB  - BACKGROUND AND AIM: Small intestinal bacterial overgrowth which has recently been
      diagnosed with the glucose breath test is characterized by excessive colonic
      bacteria in the small bowel, and results in gastrointestinal symptoms that mimic
      symptoms of inflammatory bowel disease. This study aimed to estimate the
      positivity of the glucose breath test and investigate its clinical role in
      inflammatory bowel disease. METHODS: Patients aged > 18 years with inflammatory
      bowel disease were enrolled. All patients completed symptom questionnaires. Fecal
      calprotectin level was measured to evaluate the disease activity. Thirty
      historical healthy controls were used to determine normal glucose breath test
      values. RESULTS: A total of 107 patients, 64 with ulcerative colitis and 43 with
      Crohn's disease, were included. Twenty-two patients (20.6%) were positive for the
      glucose breath test (30.2%, Crohn's disease; 14.1%, ulcerative colitis). Positive
      rate of the glucose breath test was significantly higher in patients with Crohn's
      disease than in healthy controls (30.2% vs 6.7%, P=0.014). Bloating, flatus, and
      satiety were higher in glucose breath test-positive patients than glucose breath
      test-negative patients (P=0.021, 0.014, and 0.049, respectively). The positivity
      was not correlated with the fecal calprotectin level. CONCLUSIONS: The positive
      rate of the glucose breath test was higher in patients with inflammatory bowel
      disease, especially Crohn's disease than in healthy controls; gastrointestinal
      symptoms of patients with inflammatory bowel disease were correlated with this
      positivity. Glucose breath test can be used to manage intestinal symptoms of
      patients with inflammatory bowel disease.

PMID- 25612008
TI  - A silver-alkynyl cluster encapsulating a fluorescent polyoxometalate core:
      enhanced emission and fluorescence modulation.
AB  - A new silver(I)-alkynyl cluster with a [Eu(W5O18)2](9-) polyoxoanionic core of
      [Ag42{Eu(W5O18)2}((t)BuC=C)28Cl4] [OH].H2O (1) has been designed and synthesized.
      The [Eu(W5O18)2](9-) polyoxoanion acts as a template to induce the formation of
      the surrounding 42-core Ag(I) cage. Due to the hydrophobic silver(I)-alkynyl
      shell, 1 features an unusual fluorescence enhancement as compared to the
      precursor of the [Eu(W5O18)2](9-) polyoxoanionic core. Interestingly, the silver
      ions in the shell silver(I)-alkynyl cage can only be reduced to silver atoms by
      irradiation with high energy UV light (2 kW). Upon high UV irradiation,
      fluorescence quenching of 1 has been observed. Moreover, the solution
      fluorescence of 1 can be modulated by addition of S(2-) ions into the system,
      which also leads to the fluorescence quenching phenomenon. The successful
      synthesis of 1 demonstrates a new route to the detection of high energy UV
      irradiation or S(2-) ions by elaborate design of fluorescence quenching of
      silver(I)-alkynyl clusters.

PMID- 25612009
TI  - Hierarchically porous carbon nanosheets from waste coffee grounds for
      supercapacitors.
AB  - The nanostructure design of porous carbon-based electrode materials is key to
      improving the electrochemical performance of supercapacitors. In this study,
      hierarchically porous carbon nanosheets (HP-CNSs) were fabricated using waste
      coffee grounds by in situ carbonization and activation processes using KOH.
      Despite the simple synthesis process, the HP-CNSs had a high aspect ratio
      nanostructure (~20 nm thickness to several micrometers in lateral size), a high
      specific surface area of 1945.7 m(2) g(-1), numerous heteroatoms, and good
      electrical transport properties, as well as hierarchically porous characteristics
      (0.5-10 nm in size). HP-CNS-based supercapacitors showed a specific energy of
      35.4 Wh kg(-1) at 11250 W kg(-1) and of 23 Wh kg(-1) for a 3 s charge/discharge
      current rate corresponding to a specific power of 30000 W kg(-1). Additionally,
      the HP-CNS supercapacitors demonstrated good cyclic performance over 5000 cycles.

PMID- 25612010
TI  - Effect of post-thaw storage time on motility and fertility of cryopreserved
      beluga sturgeon (Huso huso) sperm.
AB  - The aim of this study was to test the influence of post-thaw storage time on the
      duration of sperm motility, percentage of motile sperm, and fertilization and
      hatching rates of fresh sperm and sperm stored for 0, 30 and 60 min at 4 degrees
      C post-thawing. After being frozen in liquid nitrogen and then thawed, the
      percentage of motile sperm and duration of motility were not affected by 30 min
      of storage at 4 degrees C, whereas a significant decline in these parameters was
      observed after 60 min of storage. Similarly, fertilization and hatching rates
      were significantly affected within 60 min of storage at 4 degrees C, and the
      fertility of frozen-thawed sperm was significantly lower than that of fresh
      sperm. We conclude that cryopreserved sperm of beluga sturgeon could be stored
      for 30 min without the loss of sperm quality. This described procedure for beluga
      sturgeon cryopreservation is reliable and efficient and therefore can be
      recommended for hatchery practice after scaling up this technique.

PMID- 25612012
TI  - Subjective well-being and human welfare around the world as reflected in the
      Gallup World Poll.
AB  - We present data on well-being and quality of life in the world, including
      material quality of life such as not going hungry, physical health quality of
      life such as longevity, social quality of life such as social support,
      environmental health such as clean water, equality in income and life
      satisfaction, and levels of subjective well-being (SWB). There are large
      differences between nations in SWB, and these are predicted not only by economic
      development, but also by environmental health, equality and freedom in nations.
      Improving trends in SWB are seen in many countries, but declining SWB is evident
      in a few. Besides average differences in SWB between nations, there are also
      large disparities within many countries. We discuss the policy opportunities
      provided by national accounts of SWB, which are increasingly being adopted by
      many societies. They provide the opportunity to inform policy deliberations with
      well-being information that reflects not only economic development, but also
      other facets of quality of life as well. National accounts of SWB reflect the
      quality of life in areas such as health, social relationships and the natural
      environment, and therefore capture a broader view of societal well-being than
      afforded by measures of economic progress alone. 

PMID- 25612011
TI  - Identification of secretaglobin Scgb2a1 as a target for developmental
      reprogramming by BPA in the rat prostate.
AB  - Secretoglobins are a superfamily of secreted proteins thought to participate in
      inflammation, tissue repair, and tumorigenesis. Secretoglobin family 2A member 1
      (Scgb2a1) is a component of prostatein, a major androgen-binding protein secreted
      by the rat prostate. Using a rat model for developmental reprogramming of
      susceptibility to prostate carcinogenesis, we identified, by RNA-seq, that
      Scgb2a1 is significantly upregulated (>100-fold) in the prostate of adult rats
      neonatally exposed to bisphenol A (BPA), with increased gene expression confirmed
      by quantitative RT-PCR and chromatin immunoprecipitation for histone H3 lysine 9
      acetylation. Bisulfite analysis of both CpG islands located within 10 kb of the
      Scgb2a1 promoter identified significant hypomethylation of the CpG island
      upstream of the transcription start site of this gene in the reprogrammed
      prostate. These data suggest that expression of Scgb2a1 in the adult prostate
      could be epigenetically reprogrammed by BPA exposure during prostate development,
      with potential implications for cancer risk and response to chemotherapeutics
      associated with prostatein binding.

PMID- 25612014
TI  - Down to earth.

PMID- 25612013
TI  - Impact of OSA on cardiovascular events after coronary artery bypass surgery.
AB  - BACKGROUND: The impact of OSA on new cardiovascular events in patients undergoing
      coronary artery bypass graft (CABG) surgery is poorly explored. METHODS:
      Consecutive patients referred for CABG underwent clinical evaluation and standard
      polysomnography in the preoperative period. CABG surgery data, including
      percentage of off-pump and on-pump CABG, number of grafts, and intraoperative
      complications, were collected. The primary end point was major adverse cardiac or
      cerebrovascular events (MACCEs) (combined events of all-cause death, myocardial
      infarction, repeated revascularization, and cerebrovascular events). Secondary
      end points included individual MACCEs, typical angina, and arrhythmias. Patients
      were evaluated at 30 days (short-term) and up to 6.1 years (long term) after
      CABG. RESULTS: We studied 67 patients (50 men; mean age, 58 +/- 8 years; mean
      BMI, 28.5 +/- 4.1 kg/m2). OSA (apnea-hypopnea index >= 15 events/h) was present
      in 56% of the population. The patients were followed for a mean of 4.5 years
      (range, 3.2-6.1 years). No differences were observed in the short-term follow-up.
      In contrast, MACCE (35% vs 16%, P = .02), new revascularization (19% vs 0%, P =
      .01), episodes of typical angina (30% vs 7%, P = .02), and atrial fibrillation
      (22% vs 0%, P = .0068) were more common in patients with than without OSA in the
      long-term follow-up. OSA was an independent factor associated with the occurrence
      of MACCE, repeated revascularization, typical angina, and atrial fibrillation in
      the multivariate analysis. CONCLUSIONS: OSA is independently associated with a
      higher rate of long-term cardiovascular events after CABG and may have prognostic
      and economic significance in CABG surgery.

PMID- 25612015
TI  - Kept on a leash.

PMID- 25612016
TI  - Lost and found.

PMID- 25612017
TI  - Effective risk response needs a prepared mindset.

PMID- 25612029
TI  - Terrorism: Terror prediction hits limits.

PMID- 25612030
TI  - Terrorism: Science seeks roots of terror.

PMID- 25612031
TI  - Cosmology: Push to find dark matter's darling.

PMID- 25612032
TI  - Synthetic biology: Safety boost for GM organisms.

PMID- 25612033
TI  - Meteorology: California study targets rivers in the sky.

PMID- 25612036
TI  - Astronomy: Laser focus.

PMID- 25612037
TI  - Policy: Four gaps in China's new environmental law.

PMID- 25612041
TI  - Research centres: Spread excellence across Europe.

PMID- 25612035
TI  - Ageing research: Blood to blood.

PMID- 25612042
TI  - Interdisciplinary research: Bold alliances aid translational work.

PMID- 25612043
TI  - Indirect costs: The reimbursement gap.

PMID- 25612044
TI  - Satellite imaging: Disaster mapping by citizens is limited.

PMID- 25612045
TI  - Indirect costs: Cash is no gravy train.

PMID- 25612046
TI  - Catalysis: Gold unleashes the power of three.

PMID- 25612047
TI  - Astronomy: Cosmic fog and smog.

PMID- 25612048
TI  - Palaeoclimate: Monsoon matters.

PMID- 25612050
TI  - Long-lived magnetism from solidification-driven convection on the pallasite
      parent body.
AB  - Palaeomagnetic measurements of meteorites suggest that, shortly after the birth
      of the Solar System, the molten metallic cores of many small planetary bodies
      convected vigorously and were capable of generating magnetic fields. Convection
      on these bodies is currently thought to have been thermally driven, implying that
      magnetic activity would have been short-lived. Here we report a time-series
      palaeomagnetic record derived from nanomagnetic imaging of the Imilac and Esquel
      pallasite meteorites, a group of meteorites consisting of centimetre-sized
      metallic and silicate phases. We find a history of long-lived magnetic activity
      on the pallasite parent body, capturing the decay and eventual shutdown of the
      magnetic field as core solidification completed. We demonstrate that magnetic
      activity driven by progressive solidification of an inner core is consistent with
      our measured magnetic field characteristics and cooling rates. Solidification
      driven convection was probably common among small body cores, and, in contrast to
      thermally driven convection, will have led to a relatively late (hundreds of
      millions of years after accretion), long-lasting, intense and widespread epoch of
      magnetic activity among these bodies in the early Solar System.

PMID- 25612049
TI  - Stable gold(III) catalysts by oxidative addition of a carbon-carbon bond.
AB  - Low-valent late transition-metal catalysis has become indispensable to chemical
      synthesis, but homogeneous high-valent transition-metal catalysis is
      underdeveloped, mainly owing to the reactivity of high-valent transition-metal
      complexes and the challenges associated with synthesizing them. Here we report a
      carbon-carbon bond cleavage at ambient conditions by a Au(i) complex that
      generates a stable Au(iii) cationic complex. In contrast to the well-established
      soft and carbophilic Au(i) catalyst, this Au(iii) complex exhibits hard,
      oxophilic Lewis acidity. For example, we observed catalytic activation of
      alpha,beta-unsaturated aldehydes towards selective conjugate additions as well as
      activation of an unsaturated aldehyde-allene for a [2 + 2] cycloaddition
      reaction. The origin of the regioselectivity and catalytic activity was
      elucidated by X-ray crystallographic analysis of an isolated Au(iii)-activated
      cinnamaldehyde intermediate. The concepts revealed suggest a strategy for
      accessing high-valent transition-metal catalysis from readily available
      precursors.

PMID- 25612052
TI  - A new lignan with hypoglycemic activity from Tadehagi triquetrum.
AB  - A new lignan named tadehaginosin, together with a known compound 3,4-dihydro-4
      (4'-hydroxyphenyl)-5,7-dihydroxycoumarin, was isolated from the aerial part of
      Tadehagi triquetrum. The new structure was determined by various spectroscopic
      techniques ((1)H and (13)C APT, HSQC, HMBC, (1)H-(1)HCOSY, NOESY and HR-ESI-MS).
      The two isolates were evaluated for their hypoglycemic effects in vitro.
      Biological investigation showed that both of them possessed the capability to
      increase glucose consumption by HepG2 cells. 

PMID- 25612053
TI  - Improved visibility of colorectal flat tumors using image-enhanced endoscopy.
AB  - Colonoscopy is considered the gold standard for detecting colorectal tumors;
      however, conventional colonoscopy can miss flat tumors. We aimed to determine
      whether visualization of colorectal flat lesions was improved by autofluorescence
      imaging and narrow-band imaging image analysis in conjunction with a new
      endoscopy system. Eight physicians compared autofluorescent, narrow-band, and
      chromoendoscopy images to 30 corresponding white-light images of flat tumors.
      Physicians rated tumor visibility from each image set as follows: +2 (improved),
      +1 (somewhat improved), 0 (equivalent to white light), -1 (somewhat decreased),
      and -2 (decreased). The eight scores for each image were totalled and evaluated.
      Interobserver agreement was also examined. Autofluorescent, narrow-band, and
      chromoendoscopy images showed improvements of 63.3% (19/30), 6.7% (2/30), and
      73.3% (22/30), respectively, with no instances of decreased visibility.
      Autofluorescence scores were generally greater than narrow-band scores.
      Interobserver agreement was 0.65 for autofluorescence, 0.80 for narrow-band
      imaging, and 0.70 for chromoendoscopy. In conclusion, using a new endoscopy
      system in conjunction with autofluorescent imaging improved visibility of
      colorectal flat tumors, equivalent to the visibility achieved using
      chromoendoscopy. 

PMID- 25612054
TI  - Abstracts of the 16th World Meeting on Sexual Medicine, October 8-12, 2014, Sao
      Paulo, Brazil.

PMID- 25612055
TI  - Impact of a Digital Power Line Filter in the 2-Global-Flash Multifocal
      Electroretinogram of Glaucoma Patients Compared to Controls.
AB  - PURPOSE: To assess the effect of a 50 Hz power line digital filter on the
      response to a 2-global-flash multifocal electroretinogram (mfERG) in primary open
      angle glaucoma (POAG) compared to control. MATERIALS AND METHODS: A 2-global
      flash mfERG (VERISTM) was recorded (23 control, 34 POAG). Eight recordings were
      noise contaminated: 4 control, 4 POAG. Response averages from the central 10
      degrees  and 7 surrounding groups were analyzed with and without a 50 Hz digital
      filter for the following mfERG response epochs: direct component (15-45 ms), 1st
      (45-75 ms) and 2nd (75-105 ms) induced components. RESULTS: A digital 50 Hz
      filter had little effect on uncontaminated with noise waveforms but, in noisy
      recordings, changed the waveform dramatically to resemble uncontaminated
      waveforms. In controls' 50 Hz-filtered uncontaminated with noise mfERGs differed
      significantly from unfiltered responses in induced components. Uncontaminated
      with noise recordings from glaucoma patients did not differ with or without the
      notch filter (p > 0.1 for all three epochs of mfERG). The mfERG response in the
      central 10 degrees in glaucoma patients differed significantly from controls,
      whether the notch filter was used or not (p < 0.001). CONCLUSIONS: A 50 Hz notch
      filter allows grossly contaminated waveforms to be analyzed in a meaningful
      manner. With a 50 Hz filter, glaucoma patients still differed significantly from
      normal.

PMID- 25612056
TI  - Rudolf Hoppe (1922-2014).

PMID- 25612057
TI  - Complicated hydatid cyst and "air bubble" sign: a stepping-stone to correct
      diagnosis.
AB  - BACKGROUND: Hydatid cyst, or Echinococcosis, is an important helminthic zoonotic
      disease in humans that commonly affects the liver and lungs. Uncomplicated
      hydatid cysts, seen as round opaque lesions on chest radiography, are easily
      diagnosed, whereas complicated cysts (infected and or perforated) may change the
      radiographic appearance of the hydatid cyst, causing an incorrect diagnosis and
      delayed treatment. Although in radiology many signs have been described, the "air
      bubble" sign, seen in the mediastinal window of CECT as a single or multiple
      small rounded radiolucent areas with sharp margins within the periphery of a
      solid mass lesion, is being recognized as a sign with high sensitivity and
      specificity in the diagnosis of complicated hydatid cysts. CASE REPORT: A 32-year
      old female on anti-tubercular treatment for the past 3 months without any
      improvement was admitted to our hospital. CECT of the chest revealed a mass-like
      lesion with the "air bubble" sign. After 15 days the patient had a vigorous bout
      of coughing, leading to expectoration of pieces of whitish yellowish gelatinous
      membrane for the next 3 days. The ELISA result for Echinococcus was highly
      positive. On the basis of the "air bubble" sign, positive serology, and
      expectorated pieces of the membrane, the patient was diagnosed as having a
      complicated hydatid cyst. CONCLUSIONS: Due to the varied presentations of
      complicated hydatid cyst, the knowledge and awareness of various signs in
      radiology associated with the hydatid cyst, in particular the "air bubble" sign,
      is imperative in making a prompt and accurate diagnosis of a complicated hydatid
      cyst.

PMID- 25612058
TI  - Intra-individual reaction time variability based on ex-Gaussian distribution as a
      potential endophenotype for attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Intra-individual variability in reaction time (IIV-RT), defined by
      standard deviation of RT (RTSD), is considered as an endophenotype for attention
      deficit/hyperactivity disorder (ADHD). Ex-Gaussian distributions of RT, rather
      than RTSD, could better characterize moment-to-moment fluctuations in
      neuropsychological performance. However, data of response variability based on ex
      Gaussian parameters as an endophenotypic candidate for ADHD are lacking. METHOD:
      We assessed 411 adolescents with clinically diagnosed ADHD based on the DSM-IV-TR
      criteria as probands, 138 unaffected siblings, and 138 healthy controls. The
      output parameters, mu, sigma, and tau, of an ex-Gaussian RT distribution were
      derived from the Conners' continuous performance test. Multi-level models
      controlling for sex, age, comorbidity, and use of methylphenidate were applied.
      RESULTS: Compared with unaffected siblings and controls, ADHD probands had
      elevated sigma value, omissions, commissions, and mean RT. Unaffected siblings
      formed an intermediate group in-between probands and controls in terms of tau
      value and RTSD. There was no between-group difference in mu value. Conforming to
      a context-dependent nature, unaffected siblings still had an intermediate tau
      value in-between probands and controls across different interstimulus intervals.
      CONCLUSION: Our findings suggest IIV-RT represented by tau may be a potential
      endophenotype for inquiry into genetic underpinnings of ADHD in the context of
      heterogeneity.

PMID- 25612059
TI  - Systematic control of photophysical properties of host materials for high quantum
      efficiency above 25% in green thermally activated delayed fluorescent devices.
AB  - Three donor-acceptor type host materials with different photophysical properties
      were developed by managing the interconnect position of the donor and acceptor
      moieties and molecular structure of the host materials was correlated with the
      electro-optical properties and device performances of the host materials. The
      linkage via the meta-position of aromatic units was better than the linkage via
      ortho- or para-positions and high quantum efficiency of 26.0% in the green
      thermally activated delayed fluorescent device was achieved using the host
      material with the meta-linkage. 

PMID- 25612060
TI  - A tobacco-free campus ambassador program and policy compliance.
AB  - OBJECTIVE: Assess impact and feasibility of a Tobacco-Free Ambassador Program on
      campus policy compliance. PARTICIPANTS: Trained Ambassadors made 253 visits to
      campus sites over 15 months to observe and/or approach violators. METHODS: Policy
      violators were observed at 23 locations during Wave 1 (April-June 2012) and/or
      Wave 2 (April-June 2013). For locations with at least 5 visits, average violators
      per visit were compared between the 2 waves using a paired t test. Attributes of
      violators were summarized. Cigarette butts were collected over 3-day periods in 4
      campus hotspots during each wave. Personnel time and cost to implement the
      program were determined. RESULTS: There were declines in observed violators per
      Ambassador visit and number of cigarette butts over time. Rate of violators per
      visit declined from 5.47 to 1.93, a 65% decrease. Personnel time was equal to 1.5
      full-time equivalents annually. CONCLUSIONS: The Ambassador Program was a
      feasible and potentially effective strategy to increase policy compliance.

PMID- 25612061
TI  - A re-evaluation of the homoploid hybrid origin of Aegilops tauschii, the donor of
      the wheat D-subgenome.

PMID- 25612062
TI  - Financial Impacts of Foot-and-Mouth Disease at Village and National Levels in Lao
      PDR.
AB  - To assist policies on Foot-and-Mouth Disease (FMD) control in Laos and the Mekong
      region, the financial impact of recent outbreaks at village and national levels
      was examined. Village-level impacts were derived from recent research on
      financial losses due to FMD per smallholder household and number of households
      with FMD-affected livestock in the village. National-level impacts of FMD were
      determined from examination of 2011-2013 FMD reported to the Lao Department of
      Livestock and Fisheries (DLF), with the 2011 epidemic reported separately due to
      the large number and size of outbreaks of FMD in that year. Estimates of the
      national financial impact of FMD were based on (i) total FMD financial losses at
      the village level and (ii) the costs of FMD responses and other related costs at
      the DLF, provincial and district levels where FMD was reported, but excluding the
      costs of revenue forgone. A Monte Carlo simulation was utilized to account for
      likelihood of FMD over- and under-reporting. Foot-and-mouth disease was recorded
      in four provinces of Phonsaly, Bokeo, Xayyabouli and Champasak in three
      consecutive years from 2011 to 2013. However, the FMD epidemic in 2011 was more
      widely distributed and involved 414 villages in 14 provinces, with thousands of
      cases of morbidity in cattle and buffalo and some mortalities. The estimated
      financial losses due to FMD in 2011 were USD 30 881(+/-23 176) at the village
      level and USD 13 512 291 at the national level based on the number of villages
      with FMD outbreaks reported. However, when the likelihood of FMD under-reporting
      was accounted for, the estimated financial losses at the national level could
      potentially increase to USD 102 094 464 (+/-52 147 261), being almost 12% of the
      estimated farm gate value of the national large ruminant herd. These findings
      confirm that FMD causes substantial financial impacts in villages and to the
      national economy of Laos, providing justification for sustained investments in
      FMD control programmes. 

PMID- 25612063
TI  - Pharmacological MRI response to a selective dopamine transporter inhibitor,
      GBR12909, in awake and anesthetized rats.
AB  - Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging
      the effects of drugs on brain activity. In preclinical phMRI studies, general
      anesthesia used for minimizing head movements is thought to influence the phMRI
      responses to drugs. In this study we investigated the phMRI responses to a
      selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA)
      releaser, d-amphetamine (AMPH), in the isoflurane anesthetized and awake rats
      using a relative cerebral blood volume (rCBV) method. AMPH (1 mg/kg i.p.) caused
      an increase in rCBV in the dopaminergic circuitry in the both anesthetized and
      awake rats. The striatal rCBV change was correlated with the change of the
      striatal DA concentration induced by AMPH in the both anesthetized and awake
      rats. GBR12909 (10 mg/kg i.p.) caused a positive rCBV response and showed a
      similar regional pattern of rCBV response to AMPH in the awake rats, and the
      correlation between the change of the striatal rCBV and the striatal DA
      concentration was observed. However, in the anesthetized rats, GBR12909 induced a
      widespread negative rCBV response, whereas an increase in striatal DA
      concentration was observed. These findings indicate that phMRI responses to
      activation of DA neurotransmission by GBR12909 or AMPH are overall identical in
      the awake state, while the phMRI response to a DAT inhibitor, GBR12909 but not to
      AMPH was changed by isoflurane anesthesia. For the evaluation of neuroactive
      drugs using phMRI, isoflurane anesthesia might be complicated the interpretation
      of pharmacodynamic effects of drugs in preclinical studies.

PMID- 25612064
TI  - Macroscopic, histochemical, and immunohistochemical comparison of hysterorrhaphy
      using catgut and chitosan suture wires.
AB  - The objective of the current article was to compare the quality of the healing
      process after hysterorrhaphy with catgut and chitosan suture wires via
      macroscopic, histochemical, and immunohistochemical evaluations. Seven ewes were
      submitted to a video-assisted laparotomy. A hysterectomy was performed with
      subsequent catgut and chitosan hysterorrhaphy in both horns. Then, macroscopic
      evaluation and biopsies of the hysterorrhaphy and control areas were carried out
      after 30 days. Although postoperative adhesion was observed in five animals of
      the catgut group, no adhesions were detected in the chitosan one. Additionally,
      there was a significant difference in increasing collagen type III and connective
      tissue for the chitosan group when compared to the control and catgut groups. A
      larger amount of blood vessels was also observed in the control group in
      comparison with the catgut and chitosan groups. Collagen type I and vascular
      endothelial growth factor-A (VEGF-A) were significantly different among groups.
      Thus, chitosan promoted a preventive effect on postoperative adhesion formation
      in the hysterorrhaphy areas, with increasing collagen type III deposition during
      tissue mending, which granted an enhanced healing process.

PMID- 25612065
TI  - Posttraumatic growth, depression and anxiety in head and neck cancer patients:
      examining their patterns and correlations in a prospective study.
AB  - BACKGROUND: Positive and negative psychological reactions have been described in
      head and neck cancer patients. Nevertheless, the relationships between these
      responses across time need to be studied to understand the patients' strengths
      and vulnerabilities. OBJECTIVES: The aim of this study is to determine the
      changes in posttraumatic growth (PTG), depression and anxiety longitudinally and
      the correlations between PTG and depression and anxiety in head and neck cancer
      patients. METHODS: A prospective study was conducted on 60 head and neck cancer
      patients within a year of diagnosis recruited from an oncology referral centre in
      Malaysia with 50 patients completing the study. The PTG Inventory-Short Form
      (PTGI-SF) and Hospital Anxiety and Depression Scale (HADS) were used at baseline
      and at 6 months follow-up. RESULTS: There were significant reductions in the
      scores of PTGI-SF (mean difference = -5.5, p = 0.014), HADS (Depression) (mean
      difference = -2.0, p < 0.05) and HADS (Anxiety) (mean difference = -2.0, p <
      0.05) from baseline to follow-up. However, their correlations were not
      significant. HADS (Depression) score at baseline showed weak inverse correlation
      with PTGI-SF score (rho = -0.147, p = 0.309), whereas PTGI-SF score had weak
      positive correlations with HADS (Anxiety) at baseline (rho = 0.261, p = 0.067),
      HADS (Depression) at follow-up (rho = 0.083, p = 0.566) and HADS (Anxiety) at
      follow-up (rho = 0.111, p = 0.445). HADS scores also did not predict total PTGI
      SF score longitudinally. CONCLUSION: There were reductions in PTG, depression and
      anxiety within a year of cancer diagnosis and 6 months later with no significant
      correlations between PTG with depression and anxiety.

PMID- 25612067
TI  - Organisation-based self-esteem mediates the effects of social support and job
      satisfaction on intention to stay in nurses.
AB  - AIM: This study examined the effect of underlying contextual factors on the
      intention to stay in nurses. BACKGROUND: Workplace promotion, social support,
      work stress, job satisfaction and organisation-based self-esteem (OBSE) are
      psychosocial factors influencing the intention to stay in nurses. However, few
      studies have analysed the relationships among these factors. METHOD: A cross
      sectional survey was conducted and a sample was recruited in convenience sampling
      method from a medical centre in Taiwan. A total of 791 nurses completed a self
      report questionnaire over a 3-month period in 2013. RESULTS: Social support, work
      stress, job satisfaction and OBSE significantly affected the intention to stay in
      nurses. Furthermore, social support and job satisfaction showed a positive direct
      effect on the intention to stay and an indirect effect on the intention to stay;
      the indirect effect was mediated by OBSE. CONCLUSION: Organisation-based self
      esteem mediates the effects of social support and job satisfaction on the
      intention to stay in nurses. IMPLICATIONS FOR NURSING MANAGEMENT: The results
      showing the influence of OBSE on the intention to stay in nurses can serve as
      insight for hospital managers to make decisions when encouraging and managing
      employees.

PMID- 25612066
TI  - Evaluation of the immunomodulatory effect of melatonin on the T-cell response in
      peripheral blood from systemic lupus erythematosus patients.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the
      production of antinuclear autoantibodies. In addition, the involvement of CD4+ T
      helper (Th) cells in SLE has become increasingly evident. Although the role of
      melatonin has been tested in some experimental models of lupus with inconclusive
      results, there are no studies evaluating the melatonin effect on cells from
      patients with SLE. Therefore, the aim of this study was to analyse the role of in
      vitro administered melatonin in the immune response of peripheral leukocytes from
      treated patients with SLE (n = 20) and age- and sex-matched healthy controls.
      Melatonin was tested for its effect on the production of key Th1, Th2, Th9, Th17
      and innate cytokines. The frequency of T regulatory (Treg) cells and the
      expression of FOXP3 and BAFF were also explored. Our results are the first to
      show that melatonin decreased the production of IL-5 and to describe the novel
      role of melatonin in IL-9 production by human circulating cells. Additionally, we
      highlighted a two-faceted melatonin effect. Although it acted as a prototypical
      anti-inflammatory compound, reducing exacerbated Th1 and innate responses in PHA
      stimulated cells from healthy subjects, it caused the opposite actions in immune
      depressed cells from patients with SLE. Melatonin also increased the number of
      Treg cells expressing FOXP3 and offset BAFF overexpression in SLE patient cells.
      These findings open a new field of research in lupus that could lead to the use
      of melatonin as treatment or cotreatment for SLE. 

PMID- 25612068
TI  - High adipose LPL activity and adipocyte hypertrophy reduce visceral fat and
      metabolic risk in obese, older women.
AB  - OBJECTIVE: To determine whether higher subcutaneous adipose tissue lipoprotein
      lipase activity (AT-LPLA) is associated with greater triglyceride (TG) storage in
      subcutaneous adipose tissue (SAT), thereby reducing visceral adipose tissue (VAT)
      accumulation and metabolic dysfunction. METHODS: Obese postmenopausal women (60
      +/- 1 years, mean +/- SEM; N = 101) had body composition measured by DXA and CT
      and had fat aspirations to measure fat cell weight (FCW) and AT-LPLA. Women were
      ranked by visceral to total abdominal fat ratio (VAT/TAF), and the lowest and
      highest groups (n = 24) matched for % fat and age. RESULTS: The prevalence of
      metabolic dysfunction was 7- to 10-fold higher in women with high VAT/TAF (Ps <
      0.01). Women with low VAT/TAF had 11% and 6% lower abdominal and gluteal FCW but
      28% and 54% higher AT-LPLA/10(6) cells in abdominal and gluteal fat,
      respectively. Abdominal FCW correlated with AT-LPLA in women with low (r = 0.63,
      P < 0.01) but not high (r = 0.14, P = 0.52) VAT/TAF, and these lines differed in
      slope (P < 0.05) and intercept (P < 0.01), suggesting greater capacity for TG
      storage with low VAT/TAF. There were no relationships between gluteal FCW and AT
      LPLA. The relationship between SAT and abdominal AT-LPLA (r = 0.39, P < 0.01)
      suggests that higher AT-LPLA promotes TG storage. CONCLUSIONS: These results
      suggest that higher AT-LPLA is associated with SAT adipocyte hypertrophy, which
      reduces visceral adiposity and metabolic risk in obese, older women.

PMID- 25612069
TI  - NF-kappaB, CRE and YY1 elements are key functional regulators of CMV promoter
      driven transient gene expression in CHO cells.
AB  - Transient gene expression (TGE) in CHO cells is utilized to produce material for
      use in early stage drug development. These systems typically utilize the
      cytomegalovirus (CMV) promoter to drive recombinant gene transcription. In this
      study, we have mechanistically dissected CMV-mediated TGE in CHO cells in order
      to identify the key regulators of this process. An in silico analysis of the
      promoter composition of transcription factor regulatory elements (TFREs) and the
      CHO cell repertoire of transcription factors identified eight TFREs as likely
      effectors of CMV activity. We determined the regulatory function of these
      elements by preventing their cognate transcription factors from binding at the
      CMV promoter. This was achieved by both scrambling promoter binding site
      sequences and using decoy molecules to sequester intracellular transcription
      factors. We determined that the vast majority of CMV activity is mediated by just
      two discrete TFREs, showing that simultaneous inhibition of NF-kappaB and CRE
      mediated transactivation reduced CMV-driven transient secreted alkaline
      phosphatase (SEAP) production by over 75%. Further, we identified a mechanism by
      which CMV-mediated TGE is negatively regulated in CHO cells, showing that
      inhibition of YY1-mediated transrepression increased SEAP production 1.5-fold.
      This work enables optimization and control of CMV-mediated TGE in CHO cells, in
      order to improve transient protein production yields. 

PMID- 25612070
TI  - Acaricidal activity of compounds from Cinnamomum camphora (L.) Presl against the
      carmine spider mite, Tetranychus cinnabarinus.
AB  - BACKGROUND: Tetranychus cinnabarinus (Boisduval) is one of the most important,
      highly polyphagous pests of a wide range of field and greenhouse crops throughout
      the world. The control of this mite is still based primarily on the use of
      synthetic chemical pesticides. In this study, we screened eight plant extracts
      from China and evaluated the natural compounds showing acaricidal properties from
      the plant extract, considering their potential use as an alternative to synthetic
      pesticides. RESULTS: In bioassay screening assays, the Cinnamomum camphora (L.)
      Presl extract showed significantly greater acaricidal activity against T.
      cinnabarinus than the other seven plant extracts tested. Five compounds were
      identified from the C. camphora extract via repeated column chromatography and
      gas chromatography-mass spectrometry analysis. All the compounds presented
      acaricidal activity, with 2,4-di-tert-butylphenol and ethyl oleate exhibiting the
      greatest activity. At 7 days after treatment in a potted seedling experiment, the
      LC50 values of 2,4-di-tert-butylphenol and ethyl oleate were found to be 1850.94
      and 2481.65 mg kg(-1) respectively. Microscopic observations showed that the
      mites displayed the symptomology of poisoning. CONCLUSION: These results
      demonstrated that the C. camphora extract and its two active components show the
      potential to be developed as new natural acaricides for controlling carmine
      spider mites.

PMID- 25612071
TI  - The relationship between worker, occupational and workplace characteristics and
      whether an injury requires time off work: a matched case-control analysis in
      Ontario, Canada.
AB  - BACKGROUND: The objective of this study was to examine individual, occupational,
      and workplace level factors associated with time loss following a similar injury.
      METHODS: Seven thousand three hundred and forty-eight workers' compensation
      claims that did not require time off work were matched with up to four claims
      that required time off work on the event, nature, and part of body injured as
      well as injury year. Conditional logistic regression models examined individual,
      occupational, and workplace level factors that were associated with the
      likelihood of not requiring time off work. RESULTS: Employees from firms with
      higher premium rates were more likely to report no time loss from work and
      workers in more physically demanding occupations were less likely to report no
      time loss from work. We observed no association between age or gender and the
      probability of a time loss claim submission. CONCLUSIONS: Our results suggest
      that insurance costs are an incentive for workplaces to adopt policies and
      practices that minimize time loss following a work injury.

PMID- 25612072
TI  - Detection of hepatitis D virus RNA carrying large fragment deletions in patients
      with severe hepatitis B/D receiving oral antiviral therapy.
AB  - A chronic lymphocytic leukemia patient had achieved complete virological
      suppression of hepatitis B virus (HBV) by oral antiviral therapy. Unexpectedly,
      fulminant hepatitis D virus (HDV) reactivation occurred, resulting in mortality.
      Cloning and sequence analysis identified a novel large fragment HDV deletion
      mutant containing only 69% of the standard genome. Reverse transcription-PCR
      assay revealed persistence of this mutant with variations of the wild-type-to
      mutant ratios during the clinical course. Serum samples from 405 patients with
      chronic hepatitis B were then submitted for HDV RNA analysis. Of them, 20 (4.9%)
      were positive for HDV RNA and 5 HDV RNA large fragment deletions were identified
      in three patients, all under entecavir treatment. Two of them suffered from acute
      hepatitis exacerbations leading to liver failure while the third had repeated
      hepatitis flares. The peak bilirubin levels in these three patients were
      significantly higher than the others without large fragment deletions (P =
      0.003). The deleted regions (527-702 bases) encompassed two ribozyme domains as
      well as part of the hepatitis D antigen (HDAg) reading frame. In conclusion,
      exacerbations of hepatitis D could occur, leading to fulminant hepatitis, even
      after complete virological suppression of HBV. Large fragment HDV RNA deletions
      were identified in some hepatitis D patients who were treated with entecavir but
      still experiencing severe hepatitis.

PMID- 25612073
TI  - Toxicity of cobalt-chromium nanoparticles released from a resurfacing hip implant
      and cobalt ions on primary human lymphocytes in vitro.
AB  - Adverse tissue responses to prostheses wear particles and released ions are
      important contributors to hip implant failure. In implant-related adverse
      reactions T-lymphocytes play a prominent role in sustaining the chronic
      inflammatory response. To further understand the involvement of lymphocytes in
      metal-on-metal (MoM) implant failure, primary human lymphocytes were isolated and
      treated with cobalt-chromium (Co-Cr) wear debris and Co ions, individually, and
      in combination, for 24, 48 and 120 h. There was a significant increase in cell
      number where debris was present, as measured by the Neutral Red assay.
      Interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and tumour necrosis factor
      alpha (TNF-alpha) secretion levels significantly decreased in the presence of
      metal particles, as measured by ELISA. Interleukin-2 (IL-2) secretion levels were
      significantly decreased by both debris and Co ions. Flow cytometry analysis
      showed that the metal nanoparticles induced a significant increase in apoptosis
      after 48-h exposure. This investigation showed that prolonged exposure (120 h) to
      metal debris induces lymphocyte proliferation, suggesting that activation of
      resting lymphocytes may have occurred. Although cytokine production was affected
      mainly by metal debris, cobalt toxicity may also modulate IL-2 secretion, and
      even Co ion concentrations below the MHRA guideline levels (7 ppb) may contribute
      to the impairment of immune regulation in vivo in patients with MoM implants.

PMID- 25612074
TI  - What was bad is now good, and what was good is now bad: changes in our views and
      images of addiction and addicts.

PMID- 25612075
TI  - Brand preferences of underage drinkers who report alcohol-related fights and
      injuries.
AB  - BACKGROUND: A significant body of research has demonstrated an association
      between adolescent alcohol consumption and subsequent fights and injuries. To
      date, however, no research has identified which brands are associated with
      alcohol-related fights and injuries among underage drinkers. OBJECTIVES: We aimed
      to: (1) report the prevalence of alcohol-related fights and injuries among a
      national sample of underage drinkers in the U.S. and (2) describe the
      relationship between specific alcohol brand consumption and these alcohol-related
      negative consequences. METHODS: We recruited 1,031 self-reported drinkers (ages
      13-20 years) via an internet panel maintained by Knowledge Networks to complete
      an online survey. Respondents reported their past-month overall and brand
      specific alcohol consumption, risky drinking behavior, and past-year alcohol
      related fights and injuries. RESULTS: Over one-quarter of the respondents (26.7%,
      N = 232) reported at least one alcohol-related fight or injury in the past year.
      Heavy episodic drinkers were over six times more likely to report one of these
      negative alcohol-related consequences (AOR: 6.4, 95% CI: 4.1-9.9). Respondents of
      black race and those from higher-income households were also significantly more
      likely to report that experience (AOR: 2.2, 95% CI: 1.3-3.7; AOR: 1.8, 95% CI:
      1.1-3.0 and 1.1-3.2, respectively). We identified eight alcohol brands that were
      significantly associated with alcohol-related fights and injuries.
      CONCLUSIONS/IMPORTANCE: Alcohol-related fights and injuries were frequently
      reported by adolescent respondents. Eight alcohol brands were significantly more
      popular among drinkers who experienced these adverse consequences. These results
      point to the need for further research on brand-specific correlates of underage
      drinking and negative health outcomes.

PMID- 25612077
TI  - Direct prediction of residual dipolar couplings of small molecules in a stretched
      gel by stochastic molecular dynamics simulations.
AB  - Residual dipolar couplings are highly useful NMR parameters for calculating and
      refining molecular structures, dynamics, and interactions. For some applications,
      however, it is inevitable that the preferred orientation of a molecule in an
      alignment medium is calculated a priori. Several methods have been developed to
      predict molecular orientations and residual dipolar couplings. Being beneficial
      for macromolecules and selected small-molecule applications, such approaches lack
      sufficient accuracy for a large number of organic compounds for which the fine
      structure and eventually the flexibility of all involved molecules have to be
      considered or are limited to specific, well-studied liquid crystals. We introduce
      a simplified model for detailed all-atom molecular dynamics calculations with a
      polymer strand lined up along the principal axis as a new approach to simulate
      the preferred orientation of small to medium-sized solutes in polymer-based, gel
      type alignment media. As is shown by a first example of strychnine in a
      polystyrene/CDCl3 gel, the simulations potentially enable the accurate prediction
      of residual dipolar couplings taking into account structural details and dynamic
      averaging effects of both the polymer and the solute.

PMID- 25612076
TI  - Growth Models of Maternal Smoking Behavior: Individual and Contextual Factors.
AB  - BACKGROUND: Persistent maternal smoking during pregnancy, reduction or cessation
      during pregnancy, and smoking initiation or resumption postpartum impel further
      research to understand these behavioral patterns and opportunities for
      intervention. OBJECTIVES: We investigated heterogenous longitudinal patterns of
      smoking quantity to determine if these patterns vary across three maternal age
      groups, and whether the influence of individual and contextual risk factors
      varies by maternal age. METHODS: Separate general growth mixture models were
      estimated for mothers ages 15-25, 26-35, and 36+, allowing different empirical
      patterns of an ordinal measure of smoking behavior at six time points, from
      preconception through child entry to kindergarten. RESULTS: We identify five
      classes for mothers ages 15-25, four classes for ages 26-35, and three classes
      for ages 36+. Each age group presents classes of nonsmokers and persistent heavy
      smokers. Intermediate to these ends of the spectrum, each age group exhibited its
      own smoking classes characterized by the extent of pregnancy smoking reductions
      and postpartum behavior. In all three age groups, class membership can be
      distinguished by individual sociodemographic and behavioral characteristics. Co
      resident smokers predicted nearly all smoking classifications across age groups,
      and selected neighborhood characteristics predicted classification of younger (15
      25) and older (36+) mothers. CONCLUSIONS: The design, timing, and delivery of
      smoking prevention and cessation services, for women seeking to become pregnant
      and for women presenting for prenatal or pediatric care, are best guided by
      individual characteristics, particularly maternal age, preconception alcohol
      consumption, and postpartum depression, but neighborhood characteristics merit
      further attention for mothers at different ages.

PMID- 25612078
TI  - Change in terrestrial ecosystem water-use efficiency over the last three decades.
AB  - Defined as the ratio between gross primary productivity (GPP) and
      evapotranspiration (ET), ecosystem-scale water-use efficiency (EWUE) is an
      indicator of the adjustment of vegetation photosynthesis to water loss. The
      processes controlling EWUE are complex and reflect both a slow evolution of
      plants and plant communities as well as fast adjustments of ecosystem functioning
      to changes of limiting resources. In this study, we investigated EWUE trends from
      1982 to 2008 using data-driven models derived from satellite observations and
      process-oriented carbon cycle models. Our findings suggest positive EWUE trends
      of 0.0056, 0.0007 and 0.0001 g C m(-2)  mm(-1)  yr(-1) under the single effect of
      rising CO2 ('CO2 '), climate change ('CLIM') and nitrogen deposition ('NDEP'),
      respectively. Global patterns of EWUE trends under different scenarios suggest
      that (i) EWUE-CO2 shows global increases, (ii) EWUE-CLIM increases in mainly high
      latitudes and decreases at middle and low latitudes, (iii) EWUE-NDEP displays
      slight increasing trends except in west Siberia, eastern Europe, parts of North
      America and central Amazonia. The data-driven MTE model, however, shows a slight
      decline of EWUE during the same period (-0.0005 g C m(-2)  mm(-1)  yr(-1) ),
      which differs from process-model (0.0064 g C m(-2)  mm(-1)  yr(-1) ) simulations
      with all drivers taken into account. We attribute this discrepancy to the fact
      that the nonmodeled physiological effects of elevated CO2 reducing stomatal
      conductance and transpiration (TR) in the MTE model. Partial correlation analysis
      between EWUE and climate drivers shows similar responses to climatic variables
      with the data-driven model and the process-oriented models across different
      ecosystems. Change in water-use efficiency defined from transpiration-based WUEt
      (GPP/TR) and inherent water-use efficiency (IWUEt , GPP*VPD/TR) in response to
      rising CO2 , climate change, and nitrogen deposition are also discussed. Our
      analyses will facilitate mechanistic understanding of the carbon-water
      interactions over terrestrial ecosystems under global change. 

PMID- 25612079
TI  - Spontaneous splenic rupture following lung volume reduction surgery: an
      interesting clinical entity.

PMID- 25612080
TI  - Tipping point: Head computed tomography and its impact on neurology training.

PMID- 25612081
TI  - Validity and Intrarater Reliability of 2-Dimensional Motion Analysis Using a
      Handheld Tablet Compared to Traditional 3-Dimensional Motion Analysis.
AB  - CONTENT: Lower extremity landing mechanics have been implicated as a contributing
      factor in knee pain and injury, yet cost effective and clinically accessible
      methods for evaluating movement mechanics are limited. The identification of
      valid, reliable, and readily accessible technology to assess lower extremity
      alignment could be an important tool for clinicians, coaches, and strength and
      conditioning specialists. OBJECTIVE: The purpose of this study was to examine the
      validity and reliability of using a hand-held tablet and movement analysis
      application (app) for assessing lower extremity alignment during a drop vertical
      jump task. DESIGN: Concurrent Validation. SETTING: Laboratory. PARTICIPANTS:
      Twenty-two healthy college aged subjects (11 female and 11 male, mean age = 21 +/
      1.4 years; mean height: 1.73 +/- .12 m, mean mass: 71 +/- 13 kg) with no lower
      extremity pathology that prevented safe landing from a drop jump. INTERVENTION:
      Subjects performed six drop vertical jumps which were recorded simultaneously
      using a 3D motion capture system and a hand-held tablet. MAIN OUTCOME MEASURES:
      Angles on the tablet were calculated using a motion analysis app and from the 3D
      motion capture system using Visual 3D. Hip and knee angles were measured and
      compared between both systems. RESULTS: Significant correlations between the
      tablet and 3D measures for select frontal and sagittal plane ranges of motion
      (ROM) and angles at maximum knee flexion (MKF) ranged from r = 0.48 (P = .036)
      for frontal plane knee angle at MKF to r = .77 (P<.001) for knee flexion at MKF.
      CONCLUSION: Results of this study suggest that a hand-held tablet and app may be
      a reliable method for assessing select lower extremity joint alignments during
      drop vertical jumps, but this technology should not be used to measure absolute
      joint angles. However, sports medicine specialists could use a hand-held tablet
      to reliably record and evaluate lower extremity movement patterns on the field or
      in the clinic.

PMID- 25612082
TI  - Effect of increased intake of skimmed milk, casein, whey or water on body
      composition and leptin in overweight adolescents: a randomized trial.
AB  - BACKGROUNDS: Dairy proteins may support muscle protein synthesis and improve
      satiety in adults. However, there are limited studies using exact measures of
      body composition, especially in adolescents. OBJECTIVES: This study investigates
      the effect of milk proteins and water on body composition and leptin in
      overweight adolescents. METHODS: Subjects (n = 193) aged 12-15 years were
      randomized to drink 1 L d(-1) of skimmed milk, whey, casein (all milk-based
      drinks 35 g protein L(-1) ) or water for 12 weeks. Twenty participants dropped
      out. A pre-test control group of 32 adolescents was examined 12 weeks before
      start of intervention. Outcomes included leptin and dual-energy X-ray
      absorptiometry scanning. The effects of the milk-based drinks on body composition
      and leptin were compared with baseline, pre-test control and water. RESULTS: Lean
      mass index (LMI) increased compared to baseline (all 95% confidence intervals
      0.05-0.50 kg m(-2) , all P <= 0.009) and the pre-test control group (0.044-0.247
      kg m(-2) , P <= 0.002) for all four test drinks. Fat mass index (FMI) increased
      only for milk-based drink groups compared with baseline (0.15-0.67 kg m(-2) , P <
      0.001) and also compared with water (0.029-0.255 kg m(-2) , P <= 0.011). For pre
      test control, there was no change in FMI or LMI. Leptin increased in the casein
      (1.016-3.246 ng mL(-1) , P < 0.001; 0.952-3.294 ng mL(-1) , P < 0.001) and whey
      groups (0.135-2.273 ng mL(-1) , P = 0.027; 0.069-2.322, P = 0.038) compared with
      water and pre-test control group, respectively. CONCLUSIONS: Although milk
      proteins increased LMI in overweight adolescents, there was a concurrent increase
      in FMI and leptin, whereas water only resulted in increased LMI. Thus, increased
      water intake may be beneficial for body composition in overweight adolescents.

PMID- 25612084
TI  - WITHDRAWN: Exercise therapy for patellofemoral pain syndrome.

PMID- 25612083
TI  - Precore/Core promoter variants to predict significant fibrosis in both HBeAg
      positive and negative chronic hepatitis B.
AB  - BACKGROUND & AIMS: Assessing fibrosis is essential in patients with chronic
      hepatitis B (CHB). The objective was to investigate the relationship between
      fibrosis, host and viral factors to identify non-invasive markers of significant
      fibrosis in a large cohort of unselected, well-characterized, treatment-naive CHB
      patients. METHODS: Three hundred and seventy-seven HBsAg-positive patients (97
      HBeAg-positive and 280 HBeAg-negative, genotypes A to E) who had liver biopsy
      were consecutively included. Host and viral factors (ALT, HBsAg and HBV-DNA
      levels, HBV genotype and precore (PC)/basal core promoter (BCP) variants) were
      determined on the day of the biopsy. Fibrosis stage was assessed using METAVIR
      score. RESULTS: Thirty-nine percent of the patients had significant fibrosis
      (METAVIR F >= 2). On univariate analysis, the stages of fibrosis F >= 2 were
      associated with older age (P < 0.0001), male gender (P = 0.01), higher ALT and
      HBV-DNA levels (P < 0.0001 and P = 0.0003, respectively), the presence of BCP (P
      < 0.0001) and BCP/PC variants (P < 0.0001). On multivariate analysis, age (P <
      0.0001), the presence of HBV variants (P < 0.0001), HBV-DNA level (P = 0.0006)
      and ALT level (P = 0.02) were independently associated with significant fibrosis.
      The diagnostic accuracy of the combination (age, ALT, HBV-DNA, HBV variants) in
      predicting fibrosis F >= 2 was evidenced by a c-index of 0.76 (CI 95% 0.71-0.81).
      CONCLUSIONS: We identified strong independent risk factors (age, ALT, HBV-DNA,
      HBV variants) predicting significant fibrosis (F >= 2) independently of HBeAg
      status in patients with CHB. Patients with BCP variants have a higher risk of
      severe liver disease. The detection of these mutants may help to predict
      significant fibrosis (F >= 2).

PMID- 25612085
TI  - Uterine dehiscence during initiation of spinal anesthesia for cesarean delivery.
AB  - Uterine dehiscence is a known but uncommon complication during pregnancy. The
      symptoms of uterine dehiscence can be subclinical and usually occur during
      prolonged augmented labor in women who had previous cesarean delivery and/or are
      carrying a macrosomic baby. It can be associated with maternal and fetal
      hemodynamic compromise and complications. However, to our knowledge, spontaneous
      uterine dehiscence during performance of spinal anesthesia for an elective
      cesarean delivery has not been reported in obstetric anesthesia practice. Here,
      we report a case of uterine dehiscence while subarachnoid block was being
      performed. 

PMID- 25612086
TI  - Perioperative management for the removal of a massive ovarian cystadenoma.
AB  - We describe the perioperative management of a patient requiring removal of a 56.7
      kg ovarian cystadenoma, highlighting our techniques in managing the changes in
      the patient's respiratory, vascular, renal, and gastrointestinal systems due to
      the large mass. An appreciation of the unique physiologic and anatomical changes
      in patients with large abdominal masses allows for appropriate precautions in the
      perioperative period. 

PMID- 25612087
TI  - Probable local anesthetic systemic toxicity in a postpartum patient with acute
      Fatty liver of pregnancy after a transversus abdominis plane block.
AB  - We present the case of a 25-year-old woman with acute fatty liver of pregnancy, a
      rare mitochondrial disorder that manifests during pregnancy and has a significant
      mortality rate. Postoperative pain management is challenging for myriad reasons.
      With the increasing application of transversus abdominis plane blocks for
      postcesarean delivery analgesia, we describe the real and potential complications
      of this method of regional analgesia in patients with this disease. 

PMID- 25612088
TI  - Cardiac arrest from local anesthetic toxicity after a field block and transversus
      abdominis plane block: a consequence of miscommunication between the
      anesthesiologist and surgeon.
AB  - We report the case of a 25-year-old female scheduled for laparoscopic gynecologic
      surgery under general anesthesia. At the end of laparoscopy, an intraperitoneal
      infiltration (ropivacaine 0.75%, 20 mL) was administered by the surgeon without
      informing the anesthesiologist. After tracheal extubation due to significant
      postoperative pain, the anesthesiologist performed a bilateral transversus
      abdominis plane block (ropivacaine 0.75%, 40 mL). A seizure followed by
      ventricular arrhythmia developed 10 minutes after local anesthetic injection. An
      infusion of 20% lipid emulsion was successful in converting the ventricular
      arrhythmia to a sinus rhythm. This overdose could have been avoided with better
      communication between anesthesiologist and surgeon. 

PMID- 25612089
TI  - Editorial comment: cardiac arrest from local anesthetic toxicity after a field
      block and transversus abdominis plane block: a consequence of miscommunication
      between the anesthesiologist and surgeon and probable local anesthetic systemic
      toxicity in a postpartum patient with acute Fatty liver of pregnancy after a
      transversus abdominis plane block.

PMID- 25612090
TI  - Reduced graphene oxide supported platinum nanocubes composites: one-pot
      hydrothermal synthesis and enhanced catalytic activity.
AB  - Reduced graphene oxide (rGO) supported platinum nanocubes (Pt-NCs) composites (Pt
      NCs/rGO) were synthesized successfully by a water-based co-chemical reduction
      method, in which polyallylamine hydrochloride acted as a multi-functional
      molecule for the functionalization of graphene oxide, anchorage of Pt(II)
      precursor, and control of Pt crystal facets. The morphology, structure,
      composition, and catalytic property of Pt-NCs/rGO composites were characterized
      in detail by various spectroscopic techniques. Transmission electron microscopy
      images showed well-defined Pt-NCs with an average size of 9 nm uniformly
      distributed on the rGO surface. The as-prepared Pt-NCs/rGO composites had
      excellent colloidal stability in the aqueous solution, and exhibited superior
      catalytic activity towards the hydrogenation reduction of nitro groups compared
      to commercial Pt black. The improved catalytic activity originated from the
      abundant exposed Pt{100} facets of Pt-NCs, excellent dispersion of Pt-NCs on the
      rGO surface, and synergistic effect between Pt-NCs and rGO. 

PMID- 25612091
TI  - Establishment of a normative cepstral pediatric acoustic database.
AB  - IMPORTANCE: Few studies have used objective measures to evaluate the development
      of the normal pediatric voice. Cepstral analysis of continuous speech samples is
      a reliable method for gathering acoustic data; however, it has not been used to
      examine the changes that occur with voice development. OBJECTIVE: To establish
      and characterize acoustic patterns of the normal pediatric voice using cepstral
      analysis of voice samples from a normal pediatric voice database. DESIGN,
      SETTING, AND PARTICIPANTS: Cross-sectional study of 218 children aged 4 to 17
      years, for whom English was the primary language spoken at home, conducted at a
      pediatric otolaryngology practice and pediatric practice in a tertiary hospital
      (April 2012-May 2014). INTERVENTIONS AND EXPOSURES: Sustained vowel utterances
      and continuous speech samples (4 Consensus Auditory-Perceptual Evaluation of
      Voice [CAPE-V] and 2 sentences from the rainbow passage) were recorded and
      analyzed from children with normal voices. MAIN OUTCOMES AND MEASURES: Normal
      values were collected for the acoustic measures studied (ie, fundamental
      frequency, cepstral peak fundamental frequency, cepstral peak prominence [CPP],
      low-to-high spectral ratio [L/H ratio], and cepstral-spectral index of dysphonia
      in recorded phrases) and compiled into a normative acoustic database. RESULTS:
      Significant changes in fundamental frequency were observed with a distinct shift
      in slope at ages 11 and 14 years in boys for sustained vowel (ages 4-11 years, 
      6.83 Hz/y [P < .001]; 11-14 years, -27.62 Hz/y [P < .001]; and 14-17 years, -5.68
      Hz/y [P = .001]), all voiced (ages 4-11 years, -4.19 Hz/y [P = .002]; 11-14
      years, -29.42 Hz/y [P < .001]; and 14-17 years, -4.63 Hz/y [P < .001]), glottal
      attack (ages 4-11 years, -4.51 Hz/y; 11-14 years, -27.23 Hz/y; and 14-17 years, 
      1.70 Hz/y [P < .001 for all]), and rainbow (ages <14 years, -20.68 Hz/y [P <
      .001]; and 14-17 years, -4.50 Hz/y [P = .001]) recordings. A decreasing linear
      trend in fundamental frequency among all recordings (vowel, all voiced, easy
      onset, glottal attack, plosives, and rainbow) was found in girls (-2.56 Hz/y [P <
      .001], -3.48 Hz/y [P < .001], -2.82 Hz/y [P < .001], -3.49 Hz/y [P < .001], -2.30
      Hz/y [P < .001], and -2.98 Hz/y [P = .01], respectively). A linear increase in
      CPP was seen with age in boys, with significant changes seen in recordings for
      vowel (0.10 dB/y [P = .05]), all voiced (0.2 dB/y [P < .001]), easy onset (0.13
      dB/y [P < .001]), glottal attack (0.12 dB/y [P < .001]), plosives (0.15 dB/y [P <
      .001]), and rainbow (0.17 dB/y [P = .006]). A significant linear increase in CPP
      for girls was only seen in all voiced (0.13 dB/y [P < .001]). L/H ratio showed a
      linear increase with age among all speech samples (vowel, all voiced, easy onset,
      glottal attack, plosives, and rainbow) in boys (1.14 dB/y [P < .001], 0.92 dB/y
      [P < .001], 1.19 dB/y [P < .001], 0.79 dB/y [P < .001], 0.69 dB/y [P < .001], and
      0.54 dB/y [P = .002], respectively) and girls (0.96 dB/y, 0.60 dB/y, 0.75 dB/y,
      0.37 dB/y, 0.44 dB/y, and 0.58 dB/y, respectively [P <= .001 for all]).
      CONCLUSIONS AND RELEVANCE: This represents the first pediatric voice database
      using frequency-based acoustic measures. Our goal was to characterize the changes
      that occur in both male and female voices as children age. These findings help
      illustrate how acoustic measurements change with development and may aid in our
      understanding of the developing voice, pathologic changes, and response to
      treatment.

PMID- 25612092
TI  - Deciphering visible light photoreductive conversion of CO2 to formic acid and
      methanol using waste prepared material.
AB  - As gradual increases in atmospheric CO2 and depletion of fossil fuels have raised
      considerable public concern in recent decades, utilizing the unlimited solar
      energy to convert CO2 to fuels (e.g., formic acid and methanol) apparently could
      simultaneously resolve these issues for sustainable development. However, due to
      the complicated characteristics of CO2 reduction, the mechanism has yet to be
      disclosed. To clarify the postulated pathway as mentioned in the literature, the
      technique of electron paramagnetic resonance (ESR) was implemented herein to
      confirm the mechanism and related pathways of CO2 reduction under visible light
      using graphene-TiO2 as catalyst. The findings indicated that CO(-*) radicals, as
      the main intermediates, were first detected herein to react with several hydrogen
      ions and electrons for the formation of CH3OH. For example, the generation of CO(
      *) radicals is possibly the vital rate-controlling step for conversion of CO2 to
      methanol as hypothesized elsewhere. The kinetics behind the proposed mechanism
      was also determined in this study. The mechanism and kinetics could provide the
      in-depth understanding to the pathway of CO2 reduction and disclose system
      optimization of maximal conversion for further application. 

PMID- 25612093
TI  - Two-dimensional mineral [Pb2BiS3][AuTe2]: high-mobility charge carriers in single
      atom-thick layers.
AB  - Two-dimensional (2D) electronic systems are of wide interest due to their
      richness in chemical and physical phenomena and potential for technological
      applications. Here we report that [Pb2BiS3][AuTe2], known as the naturally
      occurring mineral buckhornite, hosts 2D carriers in single-atom-thick layers. The
      structure is composed of stacking layers of weakly coupled [Pb2BiS3] and [AuTe2]
      sheets. The insulating [Pb2BiS3] sheet inhibits interlayer charge hopping and
      confines the carriers in the basal plane of the single-atom-thick [AuTe2] layer.
      Magneto-transport measurements on synthesized samples and theoretical
      calculations show that [Pb2BiS3][AuTe2] is a multiband semimetal with a
      compensated density of electrons and holes, which exhibits a high hole carrier
      mobility of ~1360 cm(2)/(V s). This material possesses an extremely large
      anisotropy, Gamma = rho(c)/rho(ab) ~ 10(4), comparable to those of the benchmark
      2D materials graphite and Bi2Sr2CaCu2O(6+delta). The electronic structure
      features linear band dispersion at the Fermi level and ultrahigh Fermi velocities
      of 10(6) m/s, which are virtually identical to those of graphene. The weak
      interlayer coupling gives rise to the highly cleavable property of the single
      crystal specimens. Our results provide a novel candidate for a monolayer platform
      to investigate emerging electronic properties.

PMID- 25612094
TI  - Study of minor physical anomalies in complete nuclear Mexican families. Evidence
      of neurodevelopmental problems in schizophrenia.
AB  - INTRODUCTION: Minor physical anomalies (MPA) are dysmorphic features that reflect
      deviations in early development, are morphological variants that appear during
      the first trimester of pregnancy and could be used as a marker of disease risk in
      susceptible people. The literature agrees that the number of MPA is higher in
      patients with schizophrenia compared with their relatives and healthy subjects.
      The purpose of this study is to compare the MPA, assessed using the Gourion
      Scale, in complete nuclear families (families with a member with schizophrenia
      and control families) by determining the MPA mean, concordance and heritability
      for the total score on the MPA Gourion Scale for each anomaly. METHOD: The sample
      consisted of 60 families with at least one schizophrenic patient (284 members)
      and 61 control families (249 members). RESULTS: The mean total score for the
      scale was 5.72 +/- 2.3 MPA in the case of families with at least one
      schizophrenic patient and 1.8 +/- 4.46 MPA for control families. The average for
      families of patients without considering the patient in the analysis was 5.59 +/-
      2.3 MPA; for patients, the mean was 6.14 +/- 2.4 MPA. In the analysis by anomaly
      differences were found only in eleven anomalies found no evidence of heritability
      or concordance. CONCLUSIONS: MPA occur more frequently in patients, but a pattern
      of low consistency between them persists. It is concluded that MPA could be a
      marker of neurodevelopmental problems, but it is not suitable to consider them a
      Gourion scale as endophenotype.

PMID- 25612096
TI  - Allylic aminations with hindered secondary amine nucleophiles catalyzed by
      heterobimetallic Pd-Ti complexes.
AB  - Phosphinoamide-scaffolded heterobimetallic palladium-titanium complexes are
      highly effective catalysts for allylic aminations of allylic chlorides with
      hindered secondary amine nucleophiles. Three titanium-containing ligands are
      shown to assemble active catalysts in situ and enable catalysis at room
      temperature. A variety of sterically bulky secondary amines are efficiently
      allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine
      and pyrrolidine products are also efficiently generated via intramolecular
      aminations with hindered amine nucleophiles. 

PMID- 25612095
TI  - Determinants of maternal near-miss in Morocco: too late, too far, too sloppy?
AB  - BACKGROUND: In Morocco, there is little information on the circumstances
      surrounding maternal near misses. This study aimed to determine the incidence,
      characteristics, and determinants of maternal near misses in Morocco. METHOD: A
      prospective case-control study was conducted at 3 referral maternity hospitals in
      the Marrakech region of Morocco between February and July 2012. Near-miss cases
      included severe hemorrhage, hypertensive disorders, and prolonged obstructed
      labor. Three unmatched controls were selected for each near-miss case. Three
      categories of risk factors (sociodemographics, reproductive history, and delays),
      as well as perinatal outcomes, were assessed, and bivariate and multivariate
      analyses of the determinants were performed. A sample of 30 near misses and 30
      non-near misses was interviewed. RESULTS: The incidence of near misses was 120/00
      of births. Hypertensive disorders during pregnancy (45%) and severe hemorrhage
      (39%) were the most frequent direct causes of near miss. The main risk factors
      were illiteracy [OR = 2.35; 95% CI: (1.07-5.15)], lack of antenatal care [OR =
      3.97; 95% CI: (1.42-11.09)], complications during pregnancy [OR = 2.81; 95%
      CI:(1.26-6.29)], and having experienced a first phase delay [OR = 8.71; 95% CI:
      (3.97-19.12)] and a first phase of third delay [OR = 4.03; 95% CI: (1.75-9.25)].
      The main reasons for the first delay were lack of a family authority figure who
      could make a decision, lack of sufficient financial resources, lack of a vehicle,
      and fear of health facilities. The majority of near misses demonstrated a third
      delay with many referrals. The women's perceptions of the quality of their care
      highlighted the importance of information, good communication, and attitude.
      CONCLUSION: Women and newborns with serious obstetric complications have a
      greater chance of successful outcomes if they are immediately directed to a
      functioning referral hospital and if the providers are responsive.

PMID- 25612097
TI  - Prediction of a missing protein expression map in the context of the human
      proteome project.
AB  - Experimental evidence for the entire human proteome has been defined in the Human
      Proteome Project, and it is publicly available in the neXtProt database. However,
      there are still human proteins for which reliable experimental evidence does not
      exist, and the identification of such information has become one of the
      overriding objectives in the chromosome-centric study of the human proteome. With
      this aim and considering the complexity of protein detection using shotgun and
      targeted proteomics, the research community has addressed the integration of
      transcriptomics and proteomics landscapes. Here, we describe an analytical
      pipeline that predicts the probability of a missing protein being expressed in a
      biological sample based on (1) gene sequence characteristics, (2) the probability
      of an expressed gene being a coding gene of a missing protein in a certain
      sample, and (3) the probability of a gene being expressed in a transcriptomic
      experiment. More than 3400 microarray experiments were analyzed corresponding to
      three biological sources: cell lines, normal tissues, and cancer samples. A gene
      classification based on gene expression profiles distinguished among ubiquitous,
      nonubiquitous, nonexpressed, and coding genes of missing proteins. In addition, a
      different tissue-specific expression pattern for the coding genes of missing
      proteins is reported. Our results underline the relevance of selecting an
      appropriate sample for the detection of missing proteins and provide a
      comprehensive method to score their expression probability. Testis, brain, and
      skeletal muscle are the most promising normal tissues. 

PMID- 25612098
TI  - A & a case reports: a progress report and an update on requirements for patient
      consent.

PMID- 25612099
TI  - Challenges in the perioperative management of the patient receiving extended
      release naltrexone.
AB  - Patients receiving extended-release (XR) naltrexone who are having surgery
      present unique challenges to anesthesia providers, the most obvious of which is
      an altered response to the effects of opioid agonists. Based on the timing of the
      last XR naltrexone dose, patients may be refractory to the effects of opioid
      agonists or potentially more sensitive to dangerous side effects due to receptor
      upregulation and hypersensitivity. Complicating matters, redosing XR naltrexone
      soon after opioid use may precipitate opioid withdrawal. We present a case of a
      22-year-old woman receiving XR naltrexone for a history of heroin abuse
      undergoing a thyroidectomy and neck dissection. We discuss the intraoperative and
      postoperative anesthetic and analgesic planning, as well as solutions to some of
      the challenges these patients pose. 

PMID- 25612100
TI  - Editorial comment: challenges in the perioperative management of the patient
      receiving extended-release naltrexone.

PMID- 25612101
TI  - Safer tracheostomy: a proposal for the routine use of an airway exchange catheter
      during tracheostomy.
AB  - In the United States, more than 100,000 tracheostomies are performed annually.
      Many patients undergoing tracheostomy are critically ill, making them higher risk
      surgical candidates. Fortunately, the loss of airway during the procedure is
      rare, but when it occurs, the outcome can be catastrophic. In this report, we
      describe a technique to minimize the risk of airway loss by using an airway
      exchange catheter as an airway conduit during endotracheal tube removal. We
      present 2 clinical cases in which this technique was used successfully and made
      an important contribution to patient safety. 

PMID- 25612102
TI  - Prolonged pentobarbital-induced coma for the treatment of severe seizures related
      to posterior reversible encephalopathy syndrome.
AB  - In this report, we describe a case of posterior reversible encephalopathy
      syndrome in a female patient after deceased donor liver transplantation. She
      developed posterior reversible encephalopathy syndrome on postoperative day 3 and
      did not improve despite adjustments in immunosuppressive therapy. The patient had
      symptoms of severe brain edema requiring maximal therapy, which included cooling,
      mannitol, 3% saline, and a pentobarbital infusion. Attempts to lighten the level
      of sedation failed because of recurring intractable seizure activity. Reductions
      in therapeutic support were ultimately successful after 62 days of continuous
      pentobarbital therapy. The patient awoke neurologically intact and was discharged
      to a rehabilitation center in good condition. 

PMID- 25612103
TI  - Successful airway management in a patient with severe proximal achalasia requires
      interdisciplinary cooperation.
AB  - We report a case of a patient undergoing esophagectomy for end-stage achalasia, a
      rare condition associated with potentially catastrophic ventilatory and
      circulatory complications. The complexity of the case necessitated preoperative
      planning with the surgical specialist, development of a novel algorithm for
      airway management, and careful implementation of our plan. Isolation of the lungs
      from the esophagus presented unique challenges due to not only the anatomic
      derangements that are the hallmark of this disease process but also an unusual
      anatomic finding seen in this patient. 

PMID- 25612105
TI  - How to prevent overdiagnosis.
AB  - Overdiagnosis is the diagnosis of an abnormality that is not associated with a
      substantial health hazard and that patients have no benefit to be aware of. It is
      neither a misdiagnosis (diagnostic error), nor a false positive result (positive
      test in the absence of a real abnormality). It mainly results from screening, use
      of increasingly sensitive diagnostic tests, incidental findings on routine
      examinations, and widening diagnostic criteria to define a condition requiring an
      intervention. The blurring boundaries between risk and disease, physicians' fear
      of missing a diagnosis and patients' need for reassurance are further causes of
      overdiagnosis. Overdiagnosis often implies procedures to confirm or exclude the
      presence of the condition and is by definition associated with useless treatments
      and interventions, generating harm and costs without any benefit. Overdiagnosis
      also diverts healthcare professionals from caring about other health issues.
      Preventing overdiagnosis requires increasing awareness of healthcare
      professionals and patients about its occurrence, the avoidance of unnecessary and
      untargeted diagnostic tests, and the avoidance of screening without demonstrated
      benefits. Furthermore, accounting systematically for the harms and benefits of
      screening and diagnostic tests and determining risk factor thresholds based on
      the expected absolute risk reduction would also help prevent overdiagnosis. 

PMID- 25612104
TI  - Epigenetic and genetic alterations affect the WWOX gene in head and neck squamous
      cell carcinoma.
AB  - Different types of genetic and epigenetic changes are associated with HNSCC. The
      molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive
      investigation. WWOX gene expression is altered in many cancers and in a recent
      work reduced WWOX expression has been associated with miR-134 expression in
      HNSCC. In this study we investigated the WWOX messenger RNA expression levels in
      association with the promoter methylation of the WWOX gene and miR-134 expression
      levels in 80 HNSCC tumor and non-cancerous tissue samples. Our results show that
      WWOX expression is down-regulated especially in advanced-stage tumor samples or
      in tumors with SCC. This down-regulation was associated with methylation of the
      WWOX promoter region but not with miR-134 expression. There was an inverse
      correlation between the expression level and promoter methylation. We also
      analyzed whole exons and exon/intron boundries of the WWOX gene by direct
      sequencing. In our study group we observed 10 different alterations in the coding
      sequences and 18 different alterations in the non-coding sequences of the WWOX
      gene in HNSCC tumor samples. These results indicate that the WWOX gene can be
      functionally inactivated by promoter methylation, epigenetically or by mutations
      affecting the sequences coding for the enzymatic domain of the gene,
      functionally. We conclude that inactivation of WWOX gene contributes to the
      progression of HNSCC. 

PMID- 25612106
TI  - Synthesis, characterization and solid-state photoluminescence studies of six
      alkoxy phenylene ethynylene dinuclear palladium(II) rods.
AB  - A rare family of six discrete binuclear [PdCl(PEt3)2] phenylene ethynylene rods
      with alkoxy side chains (methoxy, ethoxy and heptoxy) have been developed, and
      their solid-state photoluminescence results have been presented and discussed.
      The shorter bridging ligands are of the general formula H-C=C-C6H2(R)2-C=C-H,
      where R = H, OCH3, OC2H5, and OC7H15, whereas the longer ones are based on H-C=C
      C6H4-C=C-C6H2(R)2-C=C-C6H4-C=C-H, where R = OCH3, OC2H5. These ligands display
      increasing length in both the main dimension (backbone length) as well as the
      number of carbons in the side chains (R, alkoxide side chain) that stem from the
      central phenylene moiety. The X-ray crystal structures of two of the prepared
      complexes are reported: one corresponds to a shorter rod, 1,4-bis[trans
      (PEt3)2ClPd-C=C]-2,5-diethoxybenzene (6c), while the second one is associated
      with a longer rod, the binuclear complex 1,4-bis[trans-(PEt3)2ClPd-4-(-C=C-C6H4
      C=C)]-2,5-diethoxybenzene (7c). All new compounds were characterized by NMR
      spectroscopy ((1)H, (13)C{(1)H} and (31)P{(1)H}) as well as ESI-MS(TOF), EA,
      FTIR, UV-Vis, cyclic voltammetry and solid-state photoluminescence. Our work
      shows the influence of the alkoxy side chains on the electronic structure of the
      family of binuclear Pd rods by lowering its oxidation potential. In addition to
      this, the increase of the length of the bridge results in a higher oxidation
      potential. Solid state photoluminescence results indicate that Pd complexes are
      characterized by a marked decrease in both the emission intensity and the
      fluorescence lifetime values as compared to their ligands. This behaviour could
      be due to some degree of ligand-to-metal charge transfer.

PMID- 25612107
TI  - 6-Diphenylphosphinoacenaphth-5-yl-mercurials as ligands for d(10) metals.
      Observation of closed-shell interactions of the type Hg(II)...M; M = Hg(II),
      Ag(I), Au(I).
AB  - The salt metathesis reaction of ArLi with HgCl2 produced Ar2Hg (1, Ar = 6-Ph2P
      Ace-5), which underwent complex formation with d(10)-configurated transition
      metal chlorides and triflates to give the complexes 1.HgCl2, 1.Hg(O3SCF3)2,
      1.AgCl, 1.Ag(O3SCF3), [1.Ag(NCMe)2](O3SCF3), 1.AuCl, and [1.Au](O3SCF3)
      comprising significant metallophilic interactions between Hg(II) and Hg(II),
      Ag(I), and Au(I), respectively. The transmetalation reaction of ArSnBu3 with
      HgCl2 afforded ArHgCl (2) that also forms a complex with additional HgCl2,
      namely, 2.HgCl2, which however lacks metallophilic interactions. Compounds 2 and
      1.HgCl2 possess the same elemental composition and can be interconverted in
      solution by choice of the solvent. In the presence of tetrahydrothiophene (tht),
      the complexes 1.AuCl and [1.Au](O3SCF3) underwent rearrangement into the Au(III)
      cation [cis-Ar2Au](+) ([3](+), which was isolated as Cl(-) and (O3SCF3)(-) salts)
      and elemental Hg. The reaction of 1.Hg(O3SCF3)2 with ArH produced the complex
      ArHg(ArH)(O3SCF3) (4). The metallophilic interactions are theoretically analyzed
      by a set of real-space bonding indicators derived from the atoms-in-molecules
      (AIM) and electron localizability indicator (ELI) space-partitioning schemes. 

PMID- 25612108
TI  - Successful epidural blood patch after dural tear.
AB  - Current literature reports a 3.1% incidence of durotomy with spine surgery, and
      this number increases to 15.9% with revision spine surgery. With the use of a
      blood patch to treat a dural tear, the anesthesia team was able to prevent a
      second reoperation. This treatment option offers anesthesiologists the
      opportunity to minimize further patient harm and increased cost associated with
      dural tears. 

PMID- 25612109
TI  - The preemptive use of extracorporeal membrane oxygenation to facilitate high risk
      percutaneous cardiac interventions: left main percutaneous coronary interventions
      and percutaneous balloon aortic valvuloplasty.
AB  - As percutaneous cardiac interventions continue to evolve, high-risk procedures
      are being performed on patients deemed too ill for surgery. What were once
      considered lower-risk procedures compared with open cardiac interventions may no
      longer be so because of the complex nature of the interventions and the complex
      comorbidities of the patients on whom these are being performed. We present a
      case involving high-risk percutaneous cardiac interventions (left main coronary
      angioplasty and aortic balloon valvuloplasty), facilitated by the use of
      extracorporeal membrane oxygenation in a critically ill patient with severe
      aortic stenosis, left main coronary disease, and ischemic cardiomyopathy. 

PMID- 25612110
TI  - Drager Fabius GS Ventilator Failure: An Unusual Cause.
AB  - Understanding the functioning of modern anesthesia workstations is very important
      because workstation failures in the intraoperative period may place the patient
      at risk of perioperative hypoxia and lead to unnecessary anxiety and confusion
      among anesthesia care providers. We present and simulate a critical event leading
      to Drager Fabius GS ventilator failure. 

PMID- 25612111
TI  - Manufacturer's Response to Drager Fabius GS Ventilator Failure: An Unusual Cause.

PMID- 25612112
TI  - Editorial Comment: Drager Fabius GS Ventilator Failure: An Unusual Cause.

PMID- 25612113
TI  - Antibodies armed with photosensitizers: from chemical synthesis to
      photobiological applications.
AB  - Targeting photosensitizers to cancer cells by conjugating them with specific
      antibodies, able to recognize and bind to tumor-associated antigens, is today one
      of the most attractive strategies in photodynamic therapy (PDT). This
      comprehensive review updates on chemical routes available for the preparation of
      photo-immunoconjugates (PICs), which show dual chemical and biological
      functionalities: photo-properties of the photosensitizer and the immunoreactivity
      of the antibody. Moreover, photobiological results obtained with such photo
      immunoconjugates using in vitro and in vivo cancer models are also discussed. 

PMID- 25612114
TI  - Outpatient management of intra-corporeal left ventricular assist device system in
      children: a multi-center experience.
AB  - Little is known about the outcomes of children supported on intracorporeal left
      ventricular assist device (HVAD), and the feasibility of outpatient management.
      All centers with pediatric patients discharged from the hospital on the device
      were identified using company database. A total of 14 centers were contacted,
      with 9 centers, contributing data retrospectively. From 2011 to 2013, 12
      pediatric patients (7 females), mean aged 11.9 +/- 2.3 years (range 8-15), mean
      weight 43 +/- 19 kg (range 18-81), mean body surface area 1.3 +/- 0.3 m(2) (range
      0.76-1.96) were identified. Diagnosis included: dilated cardiomyopathy (CMP) (n =
      5), noncompaction CMP (n = 4), toxic CMP (n = 2) and viral CMP (n = 1).
      Indications for support were permanent support (n = 1), bridge to recovery (n =
      1) and bridge to transplantation (n = 10). Prior to HVAD implantation, all
      patients received intravenous inotropes and two patients were on temporary
      mechanical support. Overall mortality was 0%. Mean duration of inpatient and
      outpatient support were 56 (range: 19-95 days) and 290 days (range: 42-790),
      respectively. Mean readmission rate was 0.02 per patient month (2.1 per patient).
      No adverse events involving emergency department occurred. Eight children resumed
      local schooling. Home discharge of children supported on HVAD is feasible and
      safe. School integration can be achieved. There is wide center variability to
      discharge practice for children.

PMID- 25612115
TI  - ELISPOTs Produced by CD8 and CD4 Cells Follow Log Normal Size Distribution
      Permitting Objective Counting.
AB  - Each positive well in ELISPOT assays contains spots of variable sizes that can
      range from tens of micrometers up to a millimeter in diameter. Therefore, when it
      comes to counting these spots the decision on setting the lower and the upper
      spot size thresholds to discriminate between non-specific background noise, spots
      produced by individual T cells, and spots formed by T cell clusters is critical.
      If the spot sizes follow a known statistical distribution, precise predictions on
      minimal and maximal spot sizes, belonging to a given T cell population, can be
      made. We studied the size distributional properties of IFN-gamma, IL-2, IL-4, IL
      5 and IL-17 spots elicited in ELISPOT assays with PBMC from 172 healthy donors,
      upon stimulation with 32 individual viral peptides representing defined HLA Class
      I-restricted epitopes for CD8 cells, and with protein antigens of CMV and EBV
      activating CD4 cells. A total of 334 CD8 and 80 CD4 positive T cell responses
      were analyzed. In 99.7% of the test cases, spot size distributions followed Log
      Normal function. These data formally demonstrate that it is possible to establish
      objective, statistically validated parameters for counting T cell ELISPOTs. 

PMID- 25612116
TI  - Nitric oxide and plant iron homeostasis.
AB  - Like all living organisms, plants demand iron (Fe) for important biochemical and
      metabolic processes. Internal imbalances, as a consequence of insufficient or
      excess Fe in the environment, lead to growth restriction and affect crop yield.
      Knowledge of signals and factors affecting each step in Fe uptake from the soil
      and distribution (long-distance transport, remobilization from old to young
      leaves, and storage in seeds) is necessary to improve our understanding of plant
      mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as
      a key player in maintaining Fe homeostasis through its cross talk with hormones,
      ferritin, and frataxin and the ability to form nitrosyl-iron complexes.

PMID- 25612117
TI  - The use of photodynamic therapy to treat hidradenitis suppurativa a review and
      critical analysis.
AB  - Hidradenitis Suppurativa (HS) is an inflammatory disease that results in
      abscesses, keloids, and fistulas. Acne inversa is likely to result from aberrant
      cellular immunity and dysfunction of the hair follicle in which coagulase
      negative staphylococcus (CONS) and perhaps other bacteria appear e.g
      Corynebacterium sp.to play a role by creating biofilms and stimulating the immune
      system. One treatment that has been proposed for HS is photodynamic therapy. The
      cases series reported are small and not double blinded. As of October of 2104, 8
      articles with 64 patients report success with photodynamic therapy using 5
      aminolevulinic acid (PDT-ALA) or its methyl ester (PDT-MAL). One of these 8
      reports noted superiority of the free methylene blue gel over niosomal methylene
      blue gel. Another report described success in a 27-patient trial using
      intralesional 5-aminolevulinic acid (ALA) in saline at a concentration of 1%.
      This was administered at a dose of 0.2 ml per cm3 and an HS fistula was
      irradiated by a continuous 630-nm laser diode through a 1-mm thick optical fiber
      to 1 Watt per cm3 for 3 minutes (180 Joules). However, 3 articles reported
      failure with PDT-ALA or pulse dye laser-mediated photodynamic therapy (PDL-PDT)
      and one article note 1 failure and 1 success. We suggest that it is the ability
      of PDT-ALA or PDT-MAL to break up the bio-film produced by CONS and other
      antibacterial effects that account for its success in treating HS in patients in
      whom bio-film plays a pivotal part of their pathogenesis. Other effects are also
      possible as well. Other mechanisms by which PDT may improve HS include cytotoxic
      effects, which cause selective cell necrosis, and immunomodulatory effects. The
      data suggests that if PDT is to be used, it should be with MAL or intralesional
      ALA. Note that there are a variety of causes of HS. These include hyperkeratosis
      of in the follicular infundibulum, aberrant cellular immunity, down regulations
      of defensins in stage III HS, and the infiltration of neutrophils, mast cells,
      plasma cells, and lymphocytes into the affected follicle, among others. However,
      it is likely that in individual cases one cause is primary and others secondary.
      In conclusion, PDT is not a first line treatment for HS but in some cases could
      be added as an adjuvant to therapies such as clindamycin and rifampin. 

PMID- 25612118
TI  - Multifocal tuberculosis verrucosa cutis.
AB  - Tuberculosis Verrucosa Cutis (TBVC), a verrucous form of cutaneous tuberculosis,
      occurs from inoculation of tubercle bacilli into the skin of a previously
      sensitized patient with moderate to high degree of immunity. This disease is now
      rare in western countries and in India; the incidence of cutaneous tuberculosis
      has fallen from 2% to 0.15%. However two recent studies from the Indian
      subcontinent have reported the prevalence of cutaneous tuebrculosis as 0.7%
      (Varshney et al) and 0.26% (Patra et al) This case is reported to demonstrate the
      indolent and extensive nature of tuberculosis verrucosa cutis in an
      immunocompetent individual and to highlight the importance of histopathology and
      empirical antitubercular therapy as an adjunct diagnostic tool. 

PMID- 25612119
TI  - Idiopathic perniosis of the buttocks and thighs - clinical report.
AB  - Perniosis manifests as inflammatory cutaneous lesions mostly located on acral
      skin in association with cold and damp conditions. Perniosis of the thighs is
      quite uncommon and has been associated in the literature with horse riding
      (equestrian perniosis) or with other recreational activities with long time
      exposure to cold and humidity. We report a rare case of perniosis of the buttocks
      and thighs in a 34-year-old healthy woman without a previous history of horse
      riding or other high-risk activities. In this case, the use of thin and tight
      clothes is believed to have been enough for the development of perniosis in this
      susceptible subject. 

PMID- 25612120
TI  - Severe cutaneous adverse reaction to telaprevir.
AB  - A 50-year-old woman presented with diffuse, intensely pruritic pink-red papules
      on her trunk and extremities three weeks after starting combination therapy with
      ribavirin, telaprevir, and interferon. She also had cervical lymphadenopathy,
      fever, eosinophilia, and transaminitis consistent with a severe drug reaction to
      telaprevir. She was started on high potency topical steroids under inpatient
      observation and recovered within two weeks. Severe cutaneous eruptions secondary
      to telaprevir have resulted in black-box warnings for potentially fatal skin
      reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms
      (DRESS) and Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN).
      Because these reactions carry acute mortality rates of 10%, prompt detection and
      treatment with steroids are important. As such, physicians should be aware of
      these potentially lethal side effects. 

PMID- 25612121
TI  - Pancreatic panniculitis.
AB  - We describe a rare case of a patient with pancreatic adenocarcinoma who presented
      initially with a rash on her lower legs. Skin biopsy showed lobular panniculitis
      and characteristic "ghost" adipocytes consistent with pancreatitic panniculitis.
      This clinical case is an interesting example where a seemingly innocuous skin
      condition heralds an underlying malignant disease process. 

PMID- 25612122
TI  - Diffuse lichenplanopilaris and multiple squamous neoplasms.
AB  - Lichen planus is an inflammatory process that can affect the skin, mucosa, and
      hair follicles. An increased risk of squamous cell carcinoma has been noted in
      lichen planus of the mucosa. Rarely, in chronic, hypertrophic lichen planus of
      the skin, squamous cell neoplasms have been reported. We report a case of new
      onset lichen planopilaris with multiple squamous cell neoplasms. 

PMID- 25612123
TI  - Unusual manifestations of ectodermal dysplasia-syndactyly syndrome type I in two
      Yemeni siblings.
AB  - Ectodermal dysplasias (EDs) are a group of genodermatoses characterized by
      malformations of tissues derived from the ectoderm, including the skin, its
      appendages (hair, nails, sweat glands), teeth, and the breasts. Ectodermal
      dysplasia syndactyly syndrome (EDSS) is a rare, newly described type of ED
      involving syndactyly. We report 2 Yemeni siblings with typical EDSS
      manifestations, including bilateral, partial cutaneous syndactyly of the fingers
      and toes; sparse, coarse, brittle scalp hair, eyebrows, and eyelashes; and
      conical, widely spaced teeth with enamel notches. In addition, the siblings
      presented with other features hitherto not described for this syndrome, such as
      adermatoglyphia, onychogryphosis, hypoplastic widely spaced nipples, hypoplastic
      thumbs, and red scalp hair. 

PMID- 25612124
TI  - Gout nodulosis: report of a rare case and brief review.
AB  - The development of tophi in the absence of prior episodes of gouty arthritis is
      unusual. We hereby present a case of a non-alcoholic, normoglycemic, and
      normotensive middle-aged man, who presented with multiple nodules distributed
      bilaterally over the dorsum of hands, feet, and elbow joints without any prior
      history of arthritis. Serum uric acid level was found to be normal. Histology was
      consistent with features of tophi. On the basis of clinical and histological
      findings, the nodules were diagnosed as gouty tophi and the patient was diagnosed
      with gouty nodulosis. Gouty nodulosis is a very rare presentation of gout and
      only a few reports exist in the medical literature. 

PMID- 25612125
TI  - Comparing burden of dermatologic disease to search interest on google trends.
AB  - Google Trends is a publicly available resource for comparing Internet search
      query frequency and trends interest in queries over time. The tool provides
      country, region, and city-specific data for term search volume on Google Search.
      Our study sought to compare the relative search interest to the burden of disease
      for the fifteen skin conditions studied by the Global Burden of Disease (GBD)
      2010 project. Searches on Google Trends were conducted by using the most
      inclusive terms and true ICD code definitions as possible for the skin conditions
      studied. We report that relative interest on Google Trends did largely correlate
      to burden of disease reported by the GBD 2010 study, though some conditions were
      either underrepresented or overrepresented. Acne and herpes were the most Googled
      skin disease terms. This study provides further insight into what may be the most
      burdensome skin diseases because those with more burdensome diseases likely
      sought out information on their condition. 

PMID- 25612126
TI  - Impact of a dermatology wiki website on dermatology education.
AB  - BACKGROUND: The Dermatology Education Wiki (dermwiki) website serves as a
      resource platform for medical students and residents. The readily accessible
      interface provides dermatology articles, survival guides, didactic lectures, and
      links to faculty talks as well as research opportunities. OBJECTIVE: To assess
      medical student and resident satisfaction with the dermwiki website. METHODS:
      Fourth-year medical students taking a dermatology elective were provided with a
      temporary password to access relevant dermwiki information. A satisfaction survey
      was created to assess whether medical students found the website helpful. Second-
      and third-year dermatology residents were also surveyed to compare satisfaction
      scores prior to and after the introduction of the dermwiki website. End-of
      rotation medical student exam scores were tabulated and compared to the average
      scores from years prior to the development of the dermwiki website. RESULTS:
      Medical students rated the dermatology elective with the dermwiki website higher
      than rotations without a wiki (8.12 vs 7.31). Students planning to go into
      dermatology were more satisfied with the dermwiki website, reported accessing the
      website more frequently (11 times vs 9.5 times), and reported more time spent
      studying (12.2 hours vs 6.7 hours) than students not going into dermatology. End
      of-rotation medical student exam scores did not differ from those prior to the
      development of the demwiki website. Ten second- and third-year dermatology
      residents unanimously stated that they were more satisfied with the program after
      the institution of the dermwiki website. CONCLUSIONS: Overall, addition of the
      dermwiki website to the dermatology elective curriculum has improved medical
      student and resident satisfaction scores. The improvement is greater among
      students planning to enter the field of dermatology. This study serves as a model
      for the incorporation of internet-based interactive tools to transform and
      supplement the learning environment.

PMID- 25612127
TI  - Dermatology on pinterest.
AB  - BACKGROUND: Pinterest is a social media internet service utilized by individuals,
      organizations, and businesses to collect and share ideas related to projects or
      interests. OBJECTIVE: The literature related to dermatology-related content on
      Pinterest is scarce. This study aims to investigate the presence of dermatology
      related content available on Pinterest. METHODS: Investigators searched five
      terms related to dermatology in the "pins" and "boards" search categories of
      pinterest. The first 20 results were evaluated for content and assigned to a
      content group of "advocacy," "informative," or "home remedies." Boards were also
      categorized as being posted by an MD or professional society versus others. The
      top ten dermatology journals were also searched for under the boards category.
      RESULTS: Informative pins were the most common (49%) followed by advocacy (37%)
      and home remedies (14%). Informative boards were the most common (53%) followed
      by home remedies (31%) and advocacy (16%).We identified that only 24% of boards
      were created by either M.D.s or advocacy organizations. The top ten dermatology
      journals identified by prior studies had little presence, with only one board
      posted by JAMA Dermatology. CONCLUSIONS: Our study contributes to a growing body
      of data that dermatology organizations are relatively absent from new social
      media sites, and Pinterest represents a potential outlet for targeted
      intervention in high-risk groups for skin disease.

PMID- 25612128
TI  - A case of primary cutaneous mucormycosis caused by minor trauma.
AB  - We present the case of a 66-year-old neutropenic man with mantle-cell lymphoma
      who presented for evaluation of a rapidly expanding necrotic eschar after a minor
      cutaneous injury. Histopathology revealed infection with Rhizopus indicating
      primary cutaneous mucormycosis. Our case reviews the presentation and management
      of this condition as well highlights the potential for minor cutaneous injuries
      in the hospital to lead to this dangerous infection. 

PMID- 25612129
TI  - Recurrent, pruritic papules on the legs.
AB  - We present a patient with recurrent, pruritic, erythematous papules to the legs. 

PMID- 25612130
TI  - A case of cutaneous larva migrans presenting in a pregnant patient.
AB  - Cutaneous larva migrans (CLM) is a pruritic dermatitis caused by migration of
      animal hookworm larvae into the skin. We present a case of CLM in a 31-year-old
      pregnant woman. The treatment of CLM relies on antihelminthic agents, such as
      thiabendazole, albendazole, and ivermectin. This case was interesting in that the
      standard treatment options previously mentioned were contraindicated owing to the
      patient's pregnancy. Cryotherapy with liquid nitrogen resulted in complete
      resolution of her lesion and symptoms. 

PMID- 25612132
TI  - Pulmonary sarcoidosis and latent tuberculosis in a patient with psoriasis treated
      with adalimumab.
AB  - Tumor necrosis factor (TNF) inhibitors are powerful biologic medications that
      have been used successfully in the treatment of a variety of inflammatory
      conditions, including psoriasis. Although TNF inhibitors are generally well
      tolerated, their use increases the risk of infections such as tuberculosis (TB),
      and paradoxically, they have been associated with development of sarcoidosis. We
      report the case of a 54-year old man with plaque psoriasis who developed a
      positive TB test and pulmonary sarcoidosis after 12 months of adalimumab
      treatment. After stopping adalimumab, his psoriasis worsened and he was started
      on ustekinumab and narrowband UVB, with improvement in symptoms. We provide a
      review of the literature and discuss treatment challenges. 

PMID- 25612131
TI  - Worn down nails after acrylic nail removal.
AB  - Worn-down nail syndrome is a nail disorder characterized by thinning of the
      distal nail plate caused by repetitive chemical or mechanical trauma. We present
      a previously undescribed source of worn-down nail syndrome caused by trauma from
      nail filing after acrylic nail removal. 

PMID- 25612133
TI  - Danazol-induced Stevens-Johnson syndrome in a patient with systemic lupus
      erythematosus.
AB  - A patient with Stevens-Johnson syndrome related to danazol is presented. 

PMID- 25612134
TI  - A large hyperplastic nodule on the abdomen.
AB  - A 65-year-old man presented with a slowly enlarging, hyperplastic cutaneous
      nodule on the abdomen that developed over a period of 20 years. Based on the
      clinical manifestation and typical histopathology, the patient received a
      diagnosis of giant basal cell carcinoma. 

PMID- 25612135
TI  - Positive coping strategies and HIV-related stigma in south India.
AB  - Whether perceived or enacted, HIV-related stigma is widespread in India, and has
      had a crippling effect on People Living with HIV/AIDS (PLHA). Research has shown
      that a positive attitude towards the illness sets a proactive framework for the
      individual to cope with his or her infection; therefore, healthy coping
      mechanisms are essential to combat HIV-related stigma. This qualitative study
      involving in-depth interviews and focus group discussions with PLHA affiliated
      with HIV support groups in South India explored positive coping strategies
      employed by PLHA to deal with HIV-related stigma. Interviews and focus group
      discussions were translated, transcribed, and analyzed for consistent themes.
      Taboos surrounding modes of transmission, perceiving sex workers as responsible
      for the spread of HIV, and avoiding associating with PLHA provided the context of
      HIV-related stigma. Despite these challenges, PLHA used several positive
      strategies, classified as Clear Knowledge and Understanding of HIV, Social
      Support and Family Well-Being, Selective Disclosure, Employment Building
      Confidence, and Participation in Positive Networks. Poor understanding of HIV and
      fears of being labeled immoral undermined healthy coping behavior, while improved
      understanding, affiliation with support groups, family support, presence of
      children, and financial independence enhanced PLHA confidence. Such positive
      coping behaviours could inform culturally relevant interventions. 

PMID- 25612138
TI  - Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk
      for migraine.
AB  - BACKGROUND: Histamine has been implicated in the pathogenesis of migraine. We
      investigated the possible association between functional single nucleotide
      polymorphisms (SNPs) in the diamine oxidase gene (DAO; chromosome 7q36.1,
      involved in histamine metabolism) and the risk for migraine. METHODS: We studied
      the frequency of the rs2052129, rs10156191, rs1049742, and rs1049793 genotypes
      and allelic variants in 197 patients with migraine and 245 healthy controls using
      a TaqMan-based qPCR Assay. RESULTS: The DAO SNP rs10156191, which is related to
      decreased DAO enzyme activity, is associated with the risk of developing
      migraine, particularly in women. The odds ratio (OR) for the defect allele
      positivity is 1.61 (95% confidence interval 1.31-2.37) for overall migraine
      patients and 2.08 (1.29-3.36) for women suffering from migraine. The association
      was not influenced by confounders such as the age at onset, the presence of aura,
      positivity of alcohol as a triggering factor, positive family history of aura, or
      family history of allergy. Multiple regression analyses did not confirm
      association with the rest of genetic factors. CONCLUSION: Our findings, which
      should be framed as hypothesis generating, suggest that DAO genotypes and allelic
      variants are associated with the risk for migraine in Caucasian Spanish people,
      especially in women.

PMID- 25612136
TI  - Hormonal contraception and the risk of HIV acquisition: an individual participant
      data meta-analysis.
AB  - BACKGROUND: Observational studies of a putative association between hormonal
      contraception (HC) and HIV acquisition have produced conflicting results. We
      conducted an individual participant data (IPD) meta-analysis of studies from sub
      Saharan Africa to compare the incidence of HIV infection in women using combined
      oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone
      acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.
      METHODS AND FINDINGS: Eligible studies measured HC exposure and incident HIV
      infection prospectively using standardized measures, enrolled women aged 15-49 y,
      recorded >=15 incident HIV infections, and measured prespecified covariates. Our
      primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random
      effects meta-analysis, controlling for region, marital status, age, number of sex
      partners, and condom use. We included 18 studies, including 37,124 women (43,613
      woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR
      for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84
      1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study
      heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV
      acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use
      (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at
      lower risk of methodological bias (compared with no HC use, aHR for DMPA use
      1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use
      0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction)
      = 0.003). Neither age nor herpes simplex virus type 2 infection status modified
      the HC-HIV relationship. CONCLUSIONS: This IPD meta-analysis found no evidence
      that COC or NET-EN use increases women's risk of HIV but adds to the evidence
      that DMPA may increase HIV risk, underscoring the need for additional safe and
      effective contraceptive options for women at high HIV risk. A randomized
      controlled trial would provide more definitive evidence about the effects of
      hormonal contraception, particularly DMPA, on HIV risk.

PMID- 25612139
TI  - Mesoporous Mn-Zr composite oxides with a crystalline wall: synthesis,
      characterization and application.
AB  - Mesoporous Mn-Zr composite oxides (M-MnZr) with a crystalline wall were designed
      and achieved by a facile one-pot evaporation-induced self-assembly (EISA)
      strategy. As proved by XRD, HRTEM and SAED characterization, the wall of the
      obtained mesoporous materials exhibited a typical tetragonal phase of ZrO2. In
      addition, the introduced manganese species were homogeneously dispersed in the
      mesoporous skeleton. N2-physisorption and TEM results showed that all the final
      materials possessed an obvious mesoporous structure accompanied by a large
      specific surface area (~120 m(2) g(-1)), big pore volume (~0.2 cm(3) g(-1)) and
      uniform pore size (~4.9 nm). In addition, the liquid phase oxidation was chosen
      as the test reaction and the excellent catalytic performance of M-MnZr
      demonstrated their potential applications in oxidation reactions. 

PMID- 25612137
TI  - Rot is a key regulator of Staphylococcus aureus biofilm formation.
AB  - Staphylococcus aureus is a significant cause of chronic biofilm infections on
      medical implants. We investigated the biofilm regulatory cascade and discovered
      that the repressor of toxins (Rot) is part of this pathway. A USA300 community
      associated methicillin-resistant S. aureus strain deficient in Rot was unable to
      form a biofilm using multiple different assays, and we found rot mutants in other
      strain lineages were also biofilm deficient. By performing a global analysis of
      transcripts and protein production controlled by Rot, we observed that all the
      secreted protease genes were up-regulated in a rot mutant, and we hypothesized
      that this regulation could be responsible for the biofilm phenotype. To
      investigate this question, we determined that Rot bound to the protease
      promoters, and we observed that activity levels of these enzymes, in particular
      the cysteine proteases, were increased in a rot mutant. By inactivating these
      proteases, biofilm capacity was restored to the mutant, demonstrating they are
      responsible for the biofilm negative phenotype. Finally, we tested the rot mutant
      in a mouse catheter model of biofilm infection and observed a significant
      reduction in biofilm burden. Thus S. aureus uses the transcription factor Rot to
      repress secreted protease levels in order to build a biofilm. 

PMID- 25612140
TI  - Australian clinical practice guidelines for the diagnosis and management of
      Barrett's esophagus and early esophageal adenocarcinoma.
AB  - Barrett's esophagus (BE), a common condition, is the only known precursor to
      esophageal adenocarcinoma (EAC). There is uncertainty about the best way to
      manage BE as most people with BE never develop EAC and most patients diagnosed
      with EAC have no preceding diagnosis of BE. Moreover, there have been recent
      advances in knowledge and practice about the management of BE and early EAC. To
      aid clinical decision making in this rapidly moving field, Cancer Council
      Australia convened an expert working party to identify pertinent clinical
      questions. The questions covered a wide range of topics including endoscopic and
      histological definitions of BE and early EAC; prevalence, incidence, natural
      history, and risk factors for BE; and methods for managing BE and early EAC. The
      latter considered modification of lifestyle factors; screening and surveillance
      strategies; and medical, endoscopic, and surgical interventions. To answer each
      question, the working party systematically reviewed the literature and developed
      a set of recommendations through consensus. Evidence underpinning each
      recommendation was rated according to quality and applicability. 

PMID- 25612141
TI  - Methane sources in arctic thermokarst lake sediments on the North Slope of
      Alaska.
AB  - The permafrost on the North Slope of Alaska is densely populated by shallow lakes
      that result from thermokarst erosion. These lakes release methane (CH4 ) derived
      from a combination of ancient thermogenic pools and contemporary biogenic
      production. Despite the potential importance of CH4 as a greenhouse gas, the
      contribution of biogenic CH4 production in arctic thermokarst lakes in Alaska is
      not currently well understood. To further advance our knowledge of CH4 dynamics
      in these lakes, we focused our study on (i) the potential for microbial CH4
      production in lake sediments, (ii) the role of sediment geochemistry in
      controlling biogenic CH4 production, and (iii) the temperature dependence of this
      process. Sediment cores were collected from one site in Siqlukaq Lake and two
      sites in Sukok Lake in late October to early November. Analyses of pore water
      geochemistry, sedimentary organic matter and lipid biomarkers, stable carbon
      isotopes, results from CH4 production experiments, and copy number of a
      methanogenic pathway-specific gene (mcrA) indicated the existence of different
      sources of CH4 in each of the lakes chosen for the study. Analysis of this
      integrated data set revealed that there is biological CH4 production in Siqlukaq
      at moderate levels, while the very low levels of CH4 detected in Sukok had a
      mixed origin, with little to no biological CH4 production. Furthermore,
      methanogenic archaea exhibited temperature-dependent use of in situ substrates
      for methanogenesis, and the amount of CH4 produced was directly related to the
      amount of labile organic matter in the sediments. This study constitutes an
      important first step in better understanding the actual contribution of biogenic
      CH4 from thermokarst lakes on the coastal plain of Alaska to the current CH4
      budgets. 

PMID- 25612142
TI  - DNA methylation profiles and biomarkers of oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) constitutes >90% of oral cancers and is the
      sixth most common malignancy among males worldwide and the fourth leading cause
      of death due to cancer among males in Taiwan. However, most patients do not
      receive a diagnosis of OSCC until the late stages, which have a lower survival
      rate. The use of molecular marker analysis to identify early-stage OSCC would
      permit optimal timing for treatments and consequently prolong survival. The aim
      of this study was to identify biomarkers of OSCC using the Illumina GoldenGate
      Methylation Cancer Panel, which comprised a total of 1,505 CpG sites covering 807
      genes. Samples of buccal mucosa resected from 40 OSCC patients and normal tissue
      samples obtained from 15 patients (normal mucosa from OSCC patients or from
      patients undergoing surgery unrelated to OSCC) were analyzed. Fms-related
      tyrosine kinase 4 (FLT4) methylation exhibited a perfect specificity for
      detecting OSCC, with an area under the receiver operating characteristic curve of
      0.91 for both all-stage and early-stage OSCC. Methylation of 7 genes (ASCL1,
      FGF3, FLT4, GAS7, KDR, TERT, and TFPI2) constitutes the top-20 panels for
      detecting OSCC. The top-20 panels for detecting early-stage OSCC contain 8 genes:
      ADCYAP1, EPHA7, FLT4, GSTM2, KDR, MT1A, NPY, and TFPI2. FLT4 RNA expression and
      methylation level were validated using RT-PCR and a pyrosequencing methylation
      assay. The median level of FLT4 expression was 2.14-fold for normal relative to
      OSCC tissue samples (P < 0.0001). Among the 8 pyrosequenced FLT4 CpG sites,
      methylation level was much higher in the OSCC samples. In conclusion, methylation
      statuses of selected genes, and especially FLT4, KDR, and TFPI2, might be of
      great potential as biomarkers for early detection of buccal OSCC.

PMID- 25612143
TI  - Phytochemical profile and bioactivity of traditional ayurvedic decoctions and
      hydro-alcoholic macerations of Boerhaavia diffusa L. and Curculigo orchioides
      Gaertn.
AB  - Decoctions (DECs) and hydro-alcoholic extracts (HEs) prepared from roots of
      Boerhaavia diffusa L. (Nyctaginaceae) and Curculigo orchioides Gaertn.
      (Hypoxidaceae) were phytochemically characterised by HPLC-DAD and profiled for
      their antioxidant, antigenotoxic and cytotoxic activities. B. diffusa DEC was
      rich in ferulic acid and vanillin, while the HE also contained boeravinone B and
      eupalitin. Both C. orchioides HE and DEC displayed the main occurrence of orcinol
      beta-d-glucoside and curculigoside A. Antioxidant activity was assayed through
      spectrophotometric DPPH, ABTS and beta-carotene bleaching test, and using (HP)TLC
      bioautographic strategies. For both crude drugs, HE was the best performing
      preparation. Properly modified SOS-Chromotest evidenced a 10% inhibition by
      phytocomplexes against 4-nitroquinoline-N-oxide, and a higher bioactivity for
      vanillin (36.60 +/- 1.68%) and ferulic acid (35.09 +/- 1.53%). C. orchioides HE
      was the preparation which showed higher cytotoxicity against drug-sensitive human
      T-lymphoblastoid cell line (CCRF-CEM) and multidrug-resistant leukaemia cell line
      (CEM/ADR5000), and eupalitin was the only pure compound to exhibit an IC50 value.

PMID- 25612144
TI  - Diffusion-sensitized ophthalmic magnetic resonance imaging free of geometric
      distortion at 3.0 and 7.0 T: a feasibility study in healthy subjects and patients
      with intraocular masses.
AB  - OBJECTIVES: This study is designed to examine the feasibility of diffusion
      sensitized multishot split-echo rapid acquisition with relaxation enhancement
      (RARE) for diffusion-weighted ophthalmic imaging free of geometric distortions at
      3.0 and 7.0 T in healthy volunteers and patients with intraocular masses.
      MATERIALS AND METHODS: A diffusion-sensitized multishot split-echo RARE (ms-RARE)
      variant is proposed as an alternative imaging strategy for diffusion-weighted
      imaging. It is compared with standard single-shot echo planar imaging (EPI) and
      readout-segmented EPI in terms of geometric distortions in a structure phantom as
      well as in vivo at 3.0 and 7.0 T. To quantify geometric distortions, center of
      gravity analysis was carried out. Apparent diffusion coefficient (ADC) mapping in
      a diffusion phantom was performed to verify the diffusion sensitization within ms
      RARE. An in vivo feasibility study in healthy volunteers (n = 10; mean age, 31 +/
      7 years; mean body mass index, 22.6 +/- 1.7 kg/m2) was conducted at 3.0 and 7.0
      T to evaluate clinical feasibility of ms-RARE. As a precursor to a broader
      clinical study, patients (n = 6; mean age, 55 +/- 12 years; mean body mass index,
      27.5 +/- 4.7 kg/m2) with an uveal melanoma and/or retinal detachment were
      examined at 3.0 and 7.0 T. In 1 case, the diseased eye was enucleated as part of
      the therapy and imaged afterward with magnetic resonance microscopy at 9.4 T.
      Macrophotography and histological investigation was carried out. For qualitative
      assessment of the image distortion, 3 independent readers reviewed and scored ms
      RARE in vivo images for all subjects in a blinded reading session. Statistical
      significance in the difference of the scores (a) obtained for the pooled ms-RARE
      data with b = 0 and 300 s/mm2 and (b) for the 3 readers was analyzed using the
      nonparametric Mann-Whitney test. RESULTS: The assessment of geometric integrity
      in phantom imaging revealed the ability of ms-RARE to produce distortion-free
      images. Unlike ms-RARE, modest displacements (2.3 +/- 1.4 pixels) from the fast
      low angle shot imaging reference were observed for readout-segmented EPI, which
      were aggravated for single-shot EPI (8.3 +/- 5.7 pixels). These observations were
      confirmed in the in vivo feasibility study including distortion-free diffusion
      weighted ophthalmic images with a 0.5 * 0.5 * 5 mm3 spatial resolution at 3.0 T
      and as good as 0.2 * 0.2 * 2 mm3 at 7.0 T. The latter represents a factor of 40
      enhancement in spatial resolution versus clinical protocols recently reported for
      diffusion-weighted imaging of the eye at 1.5 T. Mean ADC values within the
      vitreous body were (2.91 +/- 0.14) * 10-3 mm2/s at 3.0 T and (2.93 +/- 0.41) * 10
      3 mm2/s at 7.0 T. Patient data showed severe retinal detachment in the anatomical
      images. Whereas the tumor remained undetected in T1-weighted and T2-weighted
      imaging at 3.0/7.0 T, in vivo ADC mapping using ms-RARE revealed the presence of
      a uveal melanoma with a significant contrast versus the surrounding subretinal
      hemorrhage. This observation was confirmed by high-resolution ex vivo magnetic
      resonance microscopy and histology. Qualitative analysis of image distortion in
      ms-RARE images obtained for all subjects yielded a mean +/- SD image quality
      score of 1.06 +/- 0.25 for b = 0 s/mm2 and of 1.17 +/- 0.49 for b = 300 s/mm2. No
      significant interreader differences were observed for ms-RARE with a diffusion
      sensitization of b = 0 s/mm2 and 300 s/mm2. CONCLUSIONS: This work demonstrates
      the capability of diffusion-sensitized ms-RARE to acquire high-contrast, high
      spatial resolution, distortion-free images of the eye and the orbit at 3.0 and
      7.0 T. Geometric distortions that are observed for EPI-based imaging approaches
      even at lower field strengths are offset by fast spin-echo-based imaging
      techniques. The benefits of this improvement can be translated into the
      assessment of spatial arrangements of the eye segments and their masses with the
      ultimate goal to provide guidance during diagnostic treatment of ophthalmological
      diseases.

PMID- 25612145
TI  - International Prostate Symptom Score is a predictive factor of lower urinary
      tract symptoms after radical prostatectomy.
AB  - OBJECTIVE: To evaluate the impact of radical prostatectomy on lower urinary tract
      symptoms by using the International Prostate Symptom Score and International
      Prostate Symptom Score quality of life. METHODS: The present prospective study
      comprised 804 patients having localized prostate cancer who underwent radical
      prostatectomy. International Prostate Symptom Score and International Prostate
      Symptom Score quality of life were recorded preoperatively, and at 1, 3, 6, 12
      and 24 months. Two study groups were considered: group 1 included patients with
      International Prostate Symptom Score <=7 (mild) and group 2 included patients
      with International Prostate Symptom Score >=8 (moderate to severe). Student's t
      test and logistic regression were carried out to detect a predictive factor of
      International Prostate Symptom Score <=7 at 24 months. RESULTS: The mean
      International Prostate Symptom Score was 5.58 +/- 6.6, 11.12 +/- 7.1 and 7.62 +/-
      6 at baseline, 1 month and 3 months, respectively (P <0.0001). The mean quality
      of life score showed the same evolution with a significant difference at 1 and 3
      months. The mean International Prostate Symptom Score was initially 1.57 +/- 1.9
      in group 1 and 13.51 +/- 5.5 in group 2 (P <0.0001), evolving to 3.41 +/- 3.1 and
      7.69 +/- 5.8 at 24 months (P <0.0001), respectively. The mean quality of life
      score was significantly different between the groups initially, and at 6 and 12
      months with P <0.0001, P = 0.005 and P = 0.02, respectively. The multivariate
      logistic regression showed that age, prostate volume and preoperative
      International Prostate Symptom Score were independent predictive factors of
      International Prostate Symptom Score <=7 at 24 months (P <0.0001). In group 2, 47
      patients (17%) had an International Prostate Symptom Score >=8 at 24 months, 15
      of them (32%) having a QoL score >=3. CONCLUSIONS: The present study shows the
      beneficial impact of radical prostatectomy on lower urinary tract symptoms.
      However, a proportion of patients with a baseline International Prostate Symptom
      Score >=8 maintain the same score at 24 months, with worsening in quality of life
      score in one-third of them.

PMID- 25612148
TI  - Psychometric Testing of the Spanish Version of the Pain Level Outcome Scale in
      Hospitalized Patients With Acute Pain.
AB  - PURPOSE: This study aims to evaluate the psychometric properties and sensitivity
      to change of the Spanish version of the Pain Level Outcome Scale. METHODS: This
      article applied observational longitudinal validation study with patients
      suffering from acute pain at three hospitals. FINDINGS: The study included 73
      patients. Inter-rater agreement was kappa = .88 and internal consistency alpha =
      .93. Principal components analysis yielded four components that explained 81.86%
      of the variance; the correlation with the Numerical Pain Intensity Scale was r = 
      .81. CONCLUSIONS: The version with 17 indicators shows good psychometric
      properties and adequate sensitivity to change. A Spanish version of the Pain
      Level Outcome Scale with 17 indicators is proposed as a structured
      multidimensional instrument to help nurses choose the most appropriate indicators
      for assessing patients' pain.

PMID- 25612146
TI  - Food Insecurity: A Concept Analysis.
AB  - AIM: To report an analysis of the concept of food insecurity in order to (a)
      propose a theoretical model of food insecurity useful to nursing; and (b) discuss
      its implications for nursing practice, nursing research, and health promotion.
      BACKGROUND: A total of 48 million Americans are food insecure. As food insecurity
      is associated with multiple negative health effects, nursing intervention is
      warranted. DESIGN: Concept analysis. DATA SOURCES: A literature search was
      conducted in May 2014 in Scopus and MEDLINE using the exploded term "food
      insecur*." No year limit was placed. Government websites and popular media were
      searched to ensure a full understanding of the concept. REVIEW METHODS: Iterative
      analysis, using the Walker and Avant method. RESULTS: Food insecurity is defined
      by uncertain ability or inability to procure food, inability to procure enough
      food, being unable to live a healthy life, and feeling unsatisfied. A proposed
      theoretical model of food insecurity, adapted from the Socio-Ecological Model,
      identifies three layers of food insecurity (individual, community, society), with
      potential for nursing impact at each level. CONCLUSION: Nurses must work to fight
      food insecurity. There exists a potential for nursing impact that is currently
      unrealized. Nursing impact can be guided by a new conceptual model, Food
      Insecurity Within the Nursing Paradigm.

PMID- 25612147
TI  - Impact of COPD in the outcome of ICU-acquired pneumonia with and without previous
      intubation.
AB  - BACKGROUND: COPD seems related to poor outcome in patients with ventilator
      associated pneumonia (VAP). However, many patients in the ICU with COPD do not
      require intubation but can also develop pneumonia in the ICU. We, therefore,
      compared the characteristics and outcomes of patients with ICU-acquired pneumonia
      (ICUAP) with and without underlying COPD. METHODS: We prospectively assessed the
      characteristics, microbiology, systemic inflammatory response, and survival of
      279 consecutive patients with ICUAP clustered according to underlying COPD or
      not. The primary end point was 90-day survival. RESULTS: Seventy-one patients
      (25%) had COPD. The proportion of VAP was less frequent in patients with COPD: 30
      (42%) compared with 126 (61%) in patients without COPD (P = .011). Patients with
      COPD were older; were more frequently men, smokers, and alcohol abusers; and more
      frequently had previous use of noninvasive ventilation. The rate of microbiologic
      diagnosis was similar between groups, with a higher rate of Aspergillus species
      and a lower rate of Enterobacteriaceae in patients with COPD. We found lower
      levels of IL-6 and IL-8 in patients with COPD without previous intubation. The 90
      day mortality was higher in patients with COPD (40 [57%] vs 74 [37%] in patients
      without COPD, P = .003). Among others, COPD was independently associated with
      decreased 90-day survival in the overall population (adjusted hazard ratio, 1.94;
      95% CI, 1.11-3.40; P = .020); this association was observed only in patients with
      VAP but not in those without previous intubation. CONCLUSIONS: COPD was
      independently associated with decreased 90-day survival in patients with VAP but
      not in those without previous intubation.

PMID- 25612150
TI  - Culture or anonymity? Differences in proposer behaviour in Korea and Germany.
AB  - This study explores the proposer behaviour in an ultimatum game (UG) frame under
      anonymous and non-anonymous conditions among a Korean and German subject pool (n
      = 590) in comparison. Whereas the anonymous condition is represented by the
      standard UG, the non-anonymous condition integrates an aggregate of the Korean
      cultural context variables university affiliation, regional origin and seniority.
      The latter, a classic Confucian context variable, is measured by age
      differentials. The former two are impactful components of so-called Yongo
      networks, a unique Korean informal institution identical to Chinese Guanxi ties.
      Yongo networks, yet underrepresented in research, are said to be a central
      context variable to explain Korean social ties and decision-making behaviour. We
      observe significant differences between the offer behaviours of Korean and German
      subjects when exposing selected cultural variables. We argue that the behavioural
      differences observed are in fact due to culture not anonymity.

PMID- 25612149
TI  - Birth data accessibility via primary care health records to classify health
      status in a multi-ethnic population of children: an observational study.
AB  - BACKGROUND: Access to reliable birth data (birthweight (BW) and gestational age
      (GA)) is essential for the identification of individuals who are at subsequent
      health risk. AIMS: This study aimed to explore the feasibility of retrospectively
      collecting birth data for schoolchildren from parental questionnaires (PQ) and
      general practitioners (GPs) in primary care clinics, in inner city neighbourhoods
      with high density of ethnic minority and disadvantaged populations. METHODS:
      Attempts were made to obtain birth data from parents and GPs for 2,171 London
      primary schoolchildren (34% White, 29% Black African origin, 25% South Asians,
      12% Other) as part of a larger study of respiratory health. RESULTS: Information
      on BW and/or GA were obtained from parents for 2,052 (95%) children. Almost all
      parents (2,045) gave consent to access their children's health records held by
      GPs. On the basis of parental information, GPs of 1,785 children were
      successfully contacted, and GPs of 1,202 children responded. Birth data were
      retrieved for only 482 children (22% of 2,052). Missing birth data from GPs were
      associated with non-white ethnicity, non-UK born, English not the dominant
      language at home or socioeconomic disadvantage. Paired data were available in 376
      children for BW and in 407 children for GA. No significant difference in BW or GA
      was observed between PQ and GP data, with <5% difference between sources
      regardless of normal or low birth weight, or term or preterm status. CONCLUSIONS:
      Parental recall of birth data for primary schoolchildren yields high quality and
      rapid return of data, and it should be considered as a viable alternative in
      which there is limited access to birth records. It provides the potential to
      include children with an increased risk of health problems within epidemiological
      studies.

PMID- 25612153
TI  - Utility of concentration-effect modeling and simulation in a thorough QT study of
      losmapimod.
AB  - A thorough QT study was conducted in healthy volunteers with losmapimod. Four
      treatment regimens were included: a therapeutic dose (7.5 mg BID for 5 days), a
      supratherapeutic dose (20 mg QD for 5 days), a positive control (400 mg
      moxifloxacin single dose on Day 5), and placebo for 5 days. Baseline and on
      treatment ECGs were measured on Day 1 (3 timepoints predose) and Day 5,
      respectively. The primary statistical analysis failed to demonstrate a lack of
      effect of losmapimod on the QT interval leading to a positive finding. However,
      simulations using the concentration-effect model established for QTcF vs.
      losmapimod concentration at concentrations 4* the maximum concentration of the
      therapeutic dose did not exceed the regulatory thresholds of concern of 5
      milliseconds for the mean (4.57 milliseconds) and 10 milliseconds for the upper
      bound of the 90%CI (90%CI 2.88, 6.10). Modeling demonstrated that the discrepant
      results may have been due to a baseline shift after repeat dosing and baseline
      differences between the treatments. Considering the results of the concentration
      effect modeling, previous losmapimod data, and the high false-positive rate
      associated with the ICH E14 statistical analysis, the statistical analysis was
      likely a false-positive. 

PMID- 25612154
TI  - Field-evolved resistance to imidacloprid and ethiprole in populations of brown
      planthopper Nilaparvata lugens collected from across South and East Asia.
AB  - BACKGROUND: We report on the status of imidacloprid and ethiprole resistance in
      Nilaparvata lugens Stal collected from across South and East Asia over the period
      2005-2012. RESULTS: A resistance survey found that field populations had
      developed up to 220-fold resistance to imidacloprid and 223-fold resistance to
      ethiprole, and that many of the strains collected showed high levels of
      resistance to both insecticides. We also found that the cytochrome P450 CYP6ER1
      was significantly overexpressed in 12 imidacloprid-resistant populations tested
      when compared with a laboratory susceptible strain, with fold changes ranging
      from ten- to 90-fold. In contrast, another cytochrome P450 CYP6AY1, also
      implicated in imidacloprid resistance, was underexpressed in ten of the
      populations and only significantly overexpressed (3.5-fold) in a single
      population from India compared with the same susceptible strain. Further
      selection of two of the imidacloprid-resistant field strains correlated with an
      approximate threefold increase in expression of CYP6ER1. CONCLUSIONS: We conclude
      that overexpression of CYP6ER1 is associated with field-evolved resistance to
      imidacloprid in brown planthopper populations in five countries in South and East
      Asia.

PMID- 25612156
TI  - Nurses' exhaustion: the role of flow at work between job demands and job
      resources.
AB  - AIM: In the light of the job demands-resources model, this study aimed to detect
      the mediating role of flow at work between job demands and job resources on one
      side, and exhaustion on the other. BACKGROUND: In a historical period where it is
      necessary to reduce the abandonment of nursing profession, flow is a useful tool
      to investigate the factors that can promote work motivation and prevent
      psychological distress. METHOD: A cross-sectional study was conducted in a
      hospital, and 279 nurses completed a questionnaire. Analyses conducted are
      descriptive statistics, alphas, correlations and a structural equations model
      that considers the mediating role of flow at work. RESULTS: Findings show both
      the central role of job resources in determining flow at work, and the mediating
      role of flow at work in decreasing exhaustion, starting from job resources, and
      in decreasing the effect of job demands on exhaustion. Moreover, flow at work
      directly decreases exhaustion. CONCLUSIONS: Results show the relevance of
      containing job demands and provide job resources to promote positive experiences
      at work. IMPLICATIONS FOR NURSING MANAGEMENT: To promote flow at work,
      organizations should offer specific resources, such as supervisors' support, job
      autonomy, and psychological support to manage the emotional charge.

PMID- 25612155
TI  - Obesity and risk of thyroid cancer: evidence from a meta-analysis of 21
      observational studies.
AB  - BACKGROUND: Several studies have evaluated the association between obesity and
      thyroid cancer risk. However, the results remain uncertain. In this study, we
      conducted a meta-analysis to assess the association between obesity and thyroid
      cancer risk. MATERIAL/METHODS: Published literature from PubMed, EMBASE, Springer
      Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National
      Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) were
      retrieved before 10 August 2014. We included all studies that reported adjusted
      risk ratios (RRs), hazard ratios (HRs) or odds ratios (ORs), and 95% confidence
      intervals (CIs) of thyroid cancer risk. RESULTS: Thirty-two studies (n=12 620
      676) were included in this meta-analysis. Obesity was associated with a
      significantly increased risk of thyroid cancer (adjusted RR=1.33; 95% CI, 1.24
      1.42; I2=25%). In the subgroup analysis by study type, increased risk of thyroid
      cancer was found in cohort studies and case-control studies. In subgroup analysis
      by sex, both obese men and women were at significantly greater risk of thyroid
      cancer than non-obese subjects. When stratified by ethnicity, significantly
      elevated risk was observed in Caucasians and in Asians. In the age subgroup
      analysis, both young and old populations showed increased thyroid cancer risk.
      Subgroup analysis on smoking status showed that increased thyroid cancer risks
      were found in smokers and in non-smokers. In the histology subgroup analyses,
      increased risks of papillary thyroid cancer, follicular thyroid cancer, and
      anaplastic thyroid cancer were observed. However, obesity was associated with
      decreased risk of medullary thyroid cancer. CONCLUSIONS: Our results indicate
      that obesity is associated with an increased thyroid cancer risk, except
      medullary thyroid cancer.

PMID- 25612158
TI  - Higher melatonin secretion is associated with lower leukocyte and platelet counts
      in the general elderly population: the HEIJO-KYO cohort.
AB  - Circulating white blood cell (WBC) and platelet (PLT) counts are widely available
      and inexpensive cellular biomarkers of systemic inflammation and have been
      associated with a risk of cardiovascular disease, cancer, and mortality.
      Melatonin may reduce systemic inflammation through its direct and indirect
      antioxidative effect; however, the associations of melatonin secretion with
      systemic inflammation remain unclear. In this cross-sectional study on 1088
      elderly individuals (mean age, 71.8 years), we measured overnight urinary 6
      sulfatoxymelatonin excretion (UME) and WBC and PLT counts as indices of melatonin
      secretion and systemic inflammation, respectively. UME was naturally log
      transformed for linear regression models because of skewed distribution (median,
      6.8 MUg; interquartile range, 4.1-10.6 MUg). Univariate models revealed that
      higher log-transformed UME levels were significantly associated with lower WBC
      and PLT counts (P = 0.046 and 0.018). After adjusting for potential confounding
      factors significantly associated with WBC or PLT counts, higher log-transformed
      UME levels were significantly associated with lower WBC and PLT counts (WBC:
      beta, -0.143; 95% confidence interval, -0.267 to -0.020; P = 0.023; PLT: beta, 
      6.786; 95% confidence interval, -12.047 to -1.525; P = 0.012). Furthermore, the
      adjusted mean differences in WBC and PLT counts between the lowest and highest
      UME tertile groups were 0.225 * 10(9) /L and 9.480 * 10(9) /L, respectively. In
      conclusion, melatonin secretion was significantly and inversely associated with
      WBC and PLT counts in the general elderly population. The associations were
      independent of several major causes of systemic inflammation, including aging,
      obesity, smoking, hypertension, diabetes, and physical inactivity. 

PMID- 25612157
TI  - Pharmacokinetics of Gd(DO3A-Lys) and MR imaging studies in an orthotopic U87MG
      glioma tumor model.
AB  - Pharmacokinetics of Gd(DO3A-Lys), a macrocyclic gadolinium-based magnetic
      resonance imaging (MRI) contrast agent functionalized with a lysine derivative,
      was studied in Wistar rats. Kinetic data were fitted using a two-compartment
      model and revealed Gd(DO3A-Lys) to have a distribution half-life, t1/2 (alpha),
      of 1.3 min, an elimination half-life, t1/2 (beta), of 24.9 min and a large volume
      of distribution, VD , of 0.49 L/kg indicative of the agent being able to rapidly
      distribute into tissues and organs. Contrast-enhanced magnetic resonance
      angiography (CE-MRA) in an orthotopic U87MG glioma mouse model demonstrated
      considerable enhancement of both the tumor and surrounding vasculature after
      intravenous administration of Gd(DO3A-Lys). Applying dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) in the glioma of different sizes further
      showed distinct uptake characteristics and patterns of enhancement, which
      suggests the potential for differentiating changes at different stages of tumor
      growth. Our results indicate that Gd(DO3A-Lys) could be a promising candidate for
      glioma MR imaging.

PMID- 25612160
TI  - Reversible morphological transformation between polymer nanocapsules and thin
      films through dynamic covalent self-assembly.
AB  - A facile method has been developed for synthesizing polymer nanocapsules and thin
      films using multiple in-plane stitching of monomers by the formation of
      reversible disulfide linkages. Owing to the reversibility of the disulfide
      linkages, the nanostructured materials readily transform their structures in
      response to environmental changes at room temperature. For example, in reducing
      environments, the polymer nanocapsules release loaded cargo molecules. Moreover,
      reversible morphological transformations between these structures can be achieved
      by simple solvent exchanges. This work is a novel approach for the formation of
      robust nano/microstructured materials that dynamically respond to environmental
      stimuli. 

PMID- 25612159
TI  - Evidence for an altered sex ratio in clinic-referred adolescents with gender
      dysphoria.
AB  - INTRODUCTION: The number of adolescents referred to specialized gender identity
      clinics for gender dysphoria appears to be increasing and there also appears to
      be a corresponding shift in the sex ratio, from one favoring natal males to one
      favoring natal females. AIM: We conducted two quantitative studies to ascertain
      whether there has been a recent inversion of the sex ratio of adolescents
      referred for gender dysphoria. METHODS: The sex ratio of adolescents from two
      specialized gender identity clinics was examined as a function of two cohort
      periods (2006-2013 vs. prior years). Study 1 was conducted on patients from a
      clinic in Toronto, and Study 2 was conducted on patients from a clinic in
      Amsterdam. RESULTS: Across both clinics, the total sample size was 748. In both
      clinics, there was a significant change in the sex ratio of referred adolescents
      between the two cohort periods: between 2006 and 2013, the sex ratio favored
      natal females, but in the prior years, the sex ratio favored natal males. In
      Study 1 from Toronto, there was no corresponding change in the sex ratio of 6,592
      adolescents referred for other clinical problems. CONCLUSIONS: Sociological and
      sociocultural explanations are offered to account for this recent inversion in
      the sex ratio of adolescents with gender dysphoria.

PMID- 25612161
TI  - Leiomyoma of the ureter.

PMID- 25612163
TI  - Iodide-capped PbS quantum dots: full optical characterization of a versatile
      absorber.
AB  - Lead sulfide quantum dots represent an emerging photovoltaic absorber material.
      While their associated optical qualities are true for the colloidal solution
      phase, they change upon processing into thin-films. A detailed view to the
      optical key-parameters during solid-film development is presented and the limits
      and outlooks for this versatile and promising absorber are discussed. 

PMID- 25612162
TI  - A randomised controlled trial of periconal eye blockade with or without
      ultrasound guidance.
AB  - We randomly allocated 129 participants with normal eyes to periconal blockade
      with (n = 69) or without (n = 60) ultrasound guidance before cataract surgery.
      There was no difference in the rates of complication, 1/69 and 0/60,
      respectively, p = 1.0. The rate of intraconal needle placement was 1/69 with
      ultrasound and 12/60 without ultrasound, a relative risk (95% CI) of 0.07 (0.01
      0.55), p < 0.0001.

PMID- 25612164
TI  - The determination of the absolute configuration of a chiral 2,3'
      diindolylarylmethane by NMR spectroscopy.
AB  - We present the determination of the absolute configuration of a chiral 2,3'
      diindolylarylmethane 1 by using the combination of NMR spectroscopic and circular
      dichroism techniques. The results would be useful for the future study of the
      effect of chirality on the biological activity of 2,3'-diindolylarylmethanes.

PMID- 25612165
TI  - Evaluation of Corneal Microstructure in Pseudoexfoliation Syndrome and Glaucoma:
      In Vivo Scanning Laser Confocal Microscopic Study.
AB  - PURPOSE: To quantitatively evaluate corneas of patients with pseudoexfoliation
      syndrome (PXS) and pseudoexfoliation glaucoma (PXG) using in vivo scanning laser
      confocal microscopy (IVCM). MATERIALS AND METHODS: The study population comprised
      30 patients with PXS, 30 patients with PXG, and 30 normal control subjects. IVCM
      of the cornea was performed on all participants using the Rostock Cornea Module
      of the Heidelberg Retinal Tomograph (HRT). Mean outcome measures included density
      of basal epithelial cells, endothelial cells, and anterior and posterior
      keratocytes; and tortuosity and density of subbasal plexus nerves. RESULTS: Mean
      densities of basal epithelial cells, endothelial cells, anterior and posterior
      keratocytes, and subbasal nerves differed significantly among the three groups.
      Subbasal nerve densities were significantly diminished in PXS and PXG patients
      (12.36 +/- 2.89 and 6.8 +/- 3.42 mm/mm(2), respectively) compared with that of
      control subjects (16.13 +/- 3.42 mm/mm(2)) (p < 0.05). Mean densities of anterior
      and posterior stromal keratocytes were significantly lower in PXS and PXG
      patients compared with control subjects (p < 0.05). Endothelial cell densities
      were 3073.63 +/- 654.49, 2592.60 +/- 276.36, and 2110.20 +/- 620.53 cells/mm(2)
      for control, PXS, and PXG groups, respectively (p < 0.05). The percentages of
      endothelial cell polymegathism and pleomorphism were higher in PXS and PXG
      patients compared with control subjects. Endothelial cell polymegathism and
      pleomorphism were more frequently associated with PXG. CONCLUSIONS: Results of
      this study demonstrate the existence of alterations in the (i) density of cells
      in the various layers of the cornea, (ii) cellular configuration of corneal
      endothelial cells, and (iii) density/diameter of the subbasal nerve plexus in
      patients with PXS, and that such alterations are common in patients with PXG. It
      would be beneficial to employ IVCM to assess the severity of pseudoexfoliation
      keratopathy (PXK).

PMID- 25612166
TI  - Cell-free DNA testing: inadequate implementation of an outstanding technique.

PMID- 25612167
TI  - Extensive acute axonal damage in pediatric multiple sclerosis lesions.
AB  - OBJECTIVE: Axonal damage occurs early in multiple sclerosis (MS) and contributes
      to the degree of clinical disability. Children with MS more often show disabling
      and polyfocal neurological symptoms at disease onset than adults with MS. Thus,
      axonal damage may differ between pediatric and adult MS patients. METHODS: We
      analyzed axonal pathology in archival brain biopsy and autopsy samples from 19
      children with early MS. Lesions were classified according to demyelinating
      activity and presence of remyelination. Axonal density and extent of acute axonal
      damage were assessed using Bielschowsky silver impregnation and
      immunohistochemistry for amyloid precursor protein (APP), respectively. Axonal
      injury was correlated with the inflammatory infiltrate as well as clinical
      characteristics. Results were compared with data from adult MS patients. RESULTS:
      Acute axonal damage was most extensive in early active demyelinating (EA) lesions
      of pediatric patients and correlated positively with the Expanded Disability
      Status Scale at attack leading to biopsy/autopsy. Comparison with 12 adult
      patients showed a 50% increase in the extent of acute axonal damage in EA lesions
      from children compared to adults, with the highest number of APP-positive
      spheroids found prior to puberty. The extent of acute axonal damage correlated
      positively with the number of lesional macrophages. Axonal density was reduced in
      pediatric lesions irrespective of the demyelinating activity or the presence of
      remyelination. Axonal reduction was similar between children and adults.
      INTERPRETATION: Our results provide evidence for more pronounced acute axonal
      damage in inflammatory demyelinating lesions from children compared to adults.

PMID- 25612168
TI  - The crystalloid-colloid debate: Consequences of resuscitation fluid selection in
      veterinary critical care.
AB  - OBJECTIVE: To provide a comprehensive review of the current literature in human
      and veterinary medicine evaluating the impact of resuscitation fluid choice on
      patient outcome and adverse effects. DATA SOURCES: Prospective and retrospective
      studies, experimental models, and review articles in both human and veterinary
      medicine retrieved via PubMed. HUMAN DATA SYNTHESIS: A series of recent, large,
      randomized controlled trials in critically ill human patients comparing
      crystalloid versus colloid driven fluid resuscitation algorithms have
      demonstrated no outcome benefit with the use of natural or synthetic colloids.
      Synthetic colloidal solutions are associated with an increased incidence of
      adverse effects including acute kidney injury, need for renal replacement
      therapy, and coagulopathies. Further, colloidal solutions demonstrate a larger
      volume of distribution in the setting of critical illness than hypothesized.
      These findings have created controversy regarding colloid fluid resuscitation in
      critically ill patients and challenge current resuscitation strategies. A
      thorough review of the most influential human data is provided. VETERINARY DATA
      SYNTHESIS: No veterinary clinical outcome data pertaining to fluid resuscitation
      choice currently exist. Veterinary data from experimental and small clinical
      trials evaluating the coagulopathic effects of hydroxyethyl starch solutions are
      described. Data pertaining to the use of natural colloids and albumin products in
      clinical veterinary patients are reviewed. In addition, data pertaining to the
      comparative intravascular volume expansion effectiveness of different fluid types
      in canine patients are reviewed. CONCLUSIONS: Clinical data from critically ill
      human patients have failed to demonstrate an outcome advantage associated with
      colloidal fluid resuscitation and indicate that hydroxyethyl starch solutions may
      be associated with significant adverse effects, including acute kidney injury,
      need for renal replacement therapy, coagulopathies, and pathologic tissue uptake.
      The ability to apply these findings to veterinary patients is unknown; however,
      similar pathophysiology may apply, and critical re-evaluation of resuscitation
      strategies is justified.

PMID- 25612169
TI  - The rapid lipopolysaccharide-induced release of matrix metalloproteinases 9 is
      suppressed by simvastatin.
AB  - A rapid increase in matrix metalloproteinase-9 (MMP-9) expression by stimulated
      leukocytes is common in many diseases. Recent evidence suggests that the
      beneficial effects of statins are mediated in part by the suppression of MMP-9
      release. In this study, we investigated the effect of statin on MMP-9 expression
      and its antagonist, tissue inhibitor of metalloproteinase-1 (TIMP-1) in LPS
      stimulated leukocytes. Rat neutrophils and monocytes were stimulated with
      lipopolysaccharide (LPS) in the presence of simvastatin. MMP-9 secretion and mRNA
      expression were analyzed using ELISA and RT-PCR, respectively. Total MMP-9
      protein production was measured by Western blot analysis. Potential signal
      transduction pathways responsible for MMP-9 production were investigated using
      luciferase reporter assays (NF-kappaB), pull-down assays (RhoA), and
      pharmacological inhibition. Our data show that MMP-9 and TIMP-1 expression are
      differentially induced by LPS in neutrophils and monocytes. We showed that rapid
      MMP-9 release occurred mainly via secretion from intracellular stores. Moreover,
      we showed that statin significantly suppressed LPS-induced MMP-9 release and mRNA
      expression in a time- and concentration-dependent manner. We also evaluated that
      simvastain postponed the rapid LPS-induced MMP-9 release for about 20 min. In
      conclusion, we demonstrated that the suppressive effect of simvastatin on LPS
      stimulated MMP-9 release does not occur via the NF-kappaB pathway and the MAPKs
      pathway, but via the RhoA/ROCK pathway. 

PMID- 25612170
TI  - Cytotoxicity of luteolin in primary rat hepatocytes: the role of CYP3A-mediated
      ortho-benzoquinone metabolite formation and glutathione depletion.
AB  - Luteolin (LUT), an active ingredient in traditional Chinese medicines and an
      integral part of the human diet, has shown promising pharmacological activities
      with a great potential for clinical use. The purpose of this study was to
      evaluate the role of cytochrome P450 (CYP450)-mediated reactive ortho
      benzoquinone metabolites formation and glutathione (GSH) depletion in LUT-induced
      cytotoxicity in primary rat hepatocytes. A reactive ortho-benzoquinone metabolite
      was identified by liquid chromatography coupled with tandem mass spectrometry (LC
      MS/MS) in rat liver microsomes (RLMs) and rat hepatocytes. Using a specific
      chemical inhibitor method, the CYP3A subfamily was found to be responsible for
      the reactive metabolite formation in RLMs. Induction of CYP3A by dexamethasone
      enhanced LUT-induced cytotoxicity, whereas inhibition of CYP3A by ketoconazole
      (Keto) decreased the cytotoxicity. The cytotoxicity and cell apoptosis induced by
      LUT were related to the amount of reactive metabolite formation. Furthermore,
      Keto inhibited the LUT-induced GSH exhaustion. The cytotoxicity was significantly
      enhanced by pretreatment with L-buthionine sulfoximine to deplete the
      intracellular GSH. A time course experiment showed that GSH depletion by LUT was
      not via oxidation of GSH and occurred prior to the increase in 2', 7'
      dichlorofluorescein in hepatocytes. Collectively, these data suggest that CYP3A
      mediated reactive metabolite formation plays a critical role in LUT-induced
      hepatotoxicity, and the direct GSH depletion is an initiating event in LUT
      mediated cytotoxicity in primary rat hepatocytes.

PMID- 25612171
TI  - Changes in gut hormones and leptin in military personnel during operational
      deployment in Afghanistan.
AB  - OBJECTIVE: Understanding the mechanisms that drive weight loss in a lean
      population may elucidate systems that regulate normal energy homeostasis. This
      prospective study of British military volunteers investigated the effects of a 6
      month deployment to Afghanistan on energy balance and circulating concentrations
      of specific appetite-regulating hormones. METHODS: Measurements were obtained
      twice in the UK (during the Pre-deployment period) and once in Afghanistan, at
      Mid-deployment. Body mass, body composition, food intake, and appetite-regulatory
      hormones (leptin, active and total ghrelin, PYY, PP, GLP-1) were measured.
      RESULTS: Repeated measures analysis of 105 volunteers showed body mass decreased
      by 4.9% +/- 3.7% (P < 0.0001) during the first half of the deployment. Leptin
      concentrations were significantly correlated with percentage body fat at each
      time point. The reduction in percentage body fat between Pre-deployment and Mid
      deployment was 8.6%, with a corresponding 48% decrease in mean circulating
      leptin. Pre-deployment leptin and total and active ghrelin levels correlated with
      subsequent change in body mass; however. no changes were observed in the
      anorectic gut hormones GLP-1, PP, or PYY. CONCLUSIONS: These data suggest that
      changes in appetite-regulating hormones in front line military personnel occur in
      response to, but do not drive, reductions in body mass.

PMID- 25612174
TI  - 50 years ago ...

PMID- 25612172
TI  - Comparing US paediatric and adult weight classification at the transition from
      late teenage to young adulthood.
AB  - BACKGROUND: Although paediatric growth charts are recommended for weight
      assessment prior to age 20, many teenagers transition earlier to adult care where
      absolute body mass index (BMI) is used. This study examines concordance of weight
      classification in older teenagers using paediatric percentiles and adult
      thresholds. METHODS: BMI from 23 640 US teens ages 18-19 years were classified
      using paediatric BMI percentile criteria for underweight (< 5th), normal (5th to
      < 85th), overweight (85th to < 95th), obesity (>= 95th) and severe obesity (>=
      120% * 95th percentile) and adult BMI (kg m(-2) ) criteria for underweight (<
      18.5), normal (18.5-24.9), overweight (25-29.9) and obesity: class I (30-34.9),
      class II (35-39.9) and class III (>= 40). Concordance was examined using the
      kappa (kappa) statistic. Blood pressure (BP) from the same visit was classified
      hypertensive for BP >= 140/90. RESULTS: The majority of visits (72.8%) occurred
      in adult primary care. Using paediatric/adult criteria, 3.4%/5.2% were
      underweight, 66.6%/58.8% normal weight, 15.7%/21.7% overweight, 14.3%/14.3% obese
      and 4.9%/6.0% severely/class II-III obese, respectively. Paediatric and adult
      classification for underweight, normal, overweight and obesity were concordant
      for 90.3% (weighted kappa 0.87 [95% confidence interval, 0.87-0.88]). For severe
      obesity, BMI >= 120% * 95th percentile showed high agreement with BMI >= 35 kg m(
      2) (kappa 0.89 [0.88-0.91]). Normal-weight males and moderately obese females by
      paediatric BMI percentile criteria who were discordantly classified into higher
      adult weight strata had a greater proportion with hypertensive BP compared with
      concordantly classified counterparts. CONCLUSIONS: Strong agreement exists
      between US paediatric BMI percentile and adult BMI classification for older
      teenagers. Adult BMI classification may optimize BMI tracking and risk
      stratification during transition from paediatric to adult care.

PMID- 25612177
TI  - The coevolution of circumperineal color and terrestriality.
AB  - Old World monkeys (Cercopithecoidea) are unusual among primates for the high
      percentage of species exhibiting circumperineal coloration, as well as the large
      percentage of highly terrestrial species. Kingdon [1974, 1980] suggested that
      circumperineal skin coloration is functionally related to terrestriality, but
      this hypothesis has not been tested. From the literature, we collected data on
      habitat use (terrestrial/arboreal) and circumperineal coloration (present/absent)
      for 78 species. Indeed, among the 78 species surveyed here, 75% of them fall into
      either the category of colored circumperineals with terrestrial lifestyle, or of
      uncolored circumperineals with arboreal lifestyle (Chi(2)(1) = 19.550, P <
      0.001). However, conventional statistical procedures assume all taxa are equally
      related-which is not usually the case in multispecies analyses-leading to higher
      rates of both type I and II statistical errors. We performed Bayesian trait
      coevolution analyses that show that models of dependent trait evolution are not
      significantly better than models assuming independent evolution of the two traits
      (log-likelihood ratio test P = 0.396, Bayes Factor = 1). Bayesian nodal
      reconstructions of the cercopithecoid phylogeny indicate that relatively few
      trait transitions are needed to account for the distributions of the two traits.
      Further, chi-squared distributional tests show that sub-family affiliation (i.e.,
      Cercopithecinae, Colobinae) is an accurate predictor of trait status. The
      discordance of the analyses may represent the results of a few different
      evolutionary scenarios, but ultimately circumperineal coloration seems weakly
      linked to terrestrial ecology.

PMID- 25612178
TI  - Highlights of the 2014 International AIDS Conference: update from down under.
AB  - The 20th International AIDS Conference held in Melbourne, Australia, from July 20
      through July 25, 2014, provided much new data on nucleoside analogue reverse
      transcriptase inhibitor-sparing antiretroviral therapy, potential consequences of
      switching suppressive antiretroviral regimen, antiretroviral treatment with
      integrase strand transfer inhibitors, effects of antiretroviral therapy on HIV
      associated neurocognitive impairment, and hepatitis C virus (HCV) treatment in
      HIV/HCV-coinfected individuals. This article summarizes an IAS-USA continuing
      education webinar presented by Paul A. Volberding, MD, in August 2014, in which
      he focused on a few select highlights from the Conference. 

PMID- 25612179
TI  - What's new in sexually transmitted infections in the HIV care setting: focus on
      syphilis and gonorrhea.
AB  - Sexually transmitted infections are a resurgent problem in HIV disease. The
      number of new cases of syphilis among men who have sex with men has continued to
      increase, requiring renewed vigilance in screening, diagnosis, and treatment.
      Drug-resistant gonorrhea has prompted changes in treatment regimens and warrants
      continued monitoring. This article summarizes an IAS-USA continuing education
      webinar presented by Jeanne M. Marrazzo, MD, MPH, in January 2014. 

PMID- 25612180
TI  - HIV prevention: integrating biomedical and behevioral interventions.
AB  - Recommendations for HIV prevention in clinical care settings by an IAS-USA panel
      were recently published. They include recommendations on HIV testing,
      antiretroviral therapy initiation, risk-reduction counseling, and antiretroviral
      therapy adherence counseling for HIV-infected individuals. For individuals at
      risk for HIV infection, recommendations for preexposure prophylaxis, other risk
      reduction strategies, adherence counseling, and postexposure prophylaxis are
      included. Many HIV-infected individuals in the United States are not fully
      engaged in HIV care and are not virologically suppressed, thus a crucial
      component of efforts to reduce HIV transmission is moving patients through the
      HIV care continuum. This article summarizes an IAS-USA continuing education
      webinar presented by Carlos del Rio, MD, in September 2014. 

PMID- 25612181
TI  - Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with
      resolved or occult HBV infection.
AB  - Reactivation of a former hepatitis B virus (HBV) infection can be triggered by
      immunosuppressive therapy, diseases associated with an immunocompromised state,
      organ transplantation or the withdrawal of antiviral drugs. Despite the absence
      of such risk factors, a spontaneous reactivation of HBV replication occurred in
      two elderly patients with resolved or occult HBV infection. A 73-year-old male
      underwent coronary artery bypass grafting in October 2008, and was negative for
      HBsAg but positive for anti-HBs. In July 2009, his serum became positive for
      HBsAg, HBeAg and HBV DNA (6.4 log copies/ml; genotype C), but negative for anti
      HBc IgM, with abrupt elevation of the liver enzymes. The entire genomic sequence
      of HBV recovered from this patient revealed no mutations in the core promoter and
      precore regions that interfere with HBeAg production. A 76-year-old male with a
      history of endoscopic mucosal resection for esophageal cancer in 2002 and an
      initial diagnosis of diabetes mellitus in 2009, at which time he was negative for
      HBsAg. He was found to be positive for HBsAg in September 2012 during a
      laboratory examination performed prior to the resection of recurrent esophageal
      cancer, despite a low HBV load (2.1 log copies/ml). Three months later, without
      the administration of any anticancer drugs, the HBV DNA (genotype B) level
      increased to 5.1 log copies/ml. A precore G1896A variant with high quasispecies
      diversity was recovered from the patient. Aging, surgical stress and complication
      of disease(s) associated with compromised immunity, such as cancer,
      arteriosclerosis and diabetes mellitus may trigger spontaneous HBV reactivation.

PMID- 25612182
TI  - Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis
      in people with alcoholic liver disease.
AB  - BACKGROUND: The presence and progression of hepatic (liver) fibrosis into
      cirrhosis is a prognostic variable having impact on survival in people with
      alcoholic liver disease. Liver biopsy, although an invasive method, is the
      recommended 'reference standard' for diagnosis and staging of hepatic fibrosis in
      people with liver diseases. Transient elastography is a non-invasive method for
      assessing and staging hepatic fibrosis. OBJECTIVES: To determine the diagnostic
      accuracy of transient elastography for diagnosis and staging hepatic fibrosis in
      people with alcoholic liver disease when compared with liver biopsy. To identify
      the optimal cut-off values for differentiating the five stages of hepatic
      fibrosis. SEARCH METHODS: The Cochrane Hepato-Biliary Group Controlled and
      Diagnostic Test Accuracy Studies Registers, The Cochrane Library, MEDLINE
      (OvidSP), EMBASE (OvidSP), and the Science Citation Index Expanded (last search
      August 2014). SELECTION CRITERIA: Diagnostic cohort and diagnostic case-control
      study designs that assessed hepatic fibrosis in participants with alcoholic liver
      disease with transient elastography and liver biopsy, irrespective of language or
      publication status. The study participants could be of any sex and ethnic origin,
      above 16 years old, hospitalised or managed as outpatients. We excluded
      participants with viral hepatitis, autoimmunity, metabolic diseases, and toxins.
      DATA COLLECTION AND ANALYSIS: We followed the guidelines in the draft Cochrane
      Handbook for Systematic Reviews of Diagnostic Test Accuracy. MAIN RESULTS: Five
      retrospective and nine prospective cohort studies with 834 participants provided
      data for the review analyses. Authors of seven of those studies sent us
      individual participant data. The risk of bias in the included studies was high in
      all but three studies. We could identify no serious concerns regarding the
      applicability of the studies in answering the main study question of our review,
      namely to use transient elastography to diagnose hepatic fibrosis. We could not
      identify the optimal cut-off values for the fibrosis stages. The definition of
      the diagnosis of alcoholic liver disease was not provided in one study and was
      not clearly defined in two studies, but it was clear in the remaining 11 studies.
      The study authors used different liver stiffness cut-off values of transient
      elastography for the hepatic fibrosis stages.There was only one study (103
      participants) with data on hepatic fibrosis stage F1 or worse, with a cut-off of
      5.9 kPa, and reporting sensitivity of 0.83 (95% confidence interval (CI) 0.74 to
      0.90) and specificity of 0.88 (95% CI 0.47 to 1.00). The summary sensitivity and
      specificity of transient elastography for F2 or worse (seven studies with 338
      participants and with cut-offs around 7.5 kPa (range 7.00 to 7.8 kPa)) were 0.94
      and 0.89 with LR+ 8.2 and LR- 0.07, which suggests that transient elastography
      could be useful to rule out the presence of significant hepatic fibrosis, thus
      avoiding liver biopsy.Due to the wide range of cut-off values (from 8.0 to 17.0
      kPa) found in the 10 studies with 760 participants with hepatic fibrosis F3 or
      worse, we fitted a hierarchical summary receiver operating characteristic (HSROC)
      model and estimated a summary ROC (SROC) curve. The sensitivity of the 10 studies
      varied from 72% to 100% and the specificity from 59% to 89%. We performed an
      additional analysis by including the studies with a cut-off value of around and
      equal to 9.5 kPa (range 8.0 to 11.0 kPa). The summary sensitivity and specificity
      of transient elastography (eight studies with 564 participants) were 0.92 and
      0.70 with LR+ 3.1 and LR- 0.11, which suggests that transient elastography could
      also be useful to rule out the presence of severe hepatic fibrosis (F3 or worse),
      avoiding liver biopsy. We carried out a sensitivity analysis by considering only
      the studies with a cut-off value equal to 9.5 kPa and the result did not
      differ.We performed an HSROC analysis and reported an SROC curve for hepatic
      fibrosis stage F4 (cirrhosis). The HSROC analysis suggested that when the cut-off
      value changes, there is a wide variation in specificity and a more limited
      variation in sensitivity. We performed an additional analysis with the studies
      with the most commonly used cut-off value of 12.5 kPa. The summary sensitivity
      and specificity of transient elastography (seven studies with 330 participants)
      were 0.95 and 0.71 with LR+ 3.3 and LR- 0.07, which again suggests that transient
      elastography could be useful to rule out the presence of cirrhosis, avoiding
      liver biopsy. AUTHORS' CONCLUSIONS: We identified a small number of studies with
      a few participants and were unable to include several studies, which raises the
      risk of outcome reporting bias. With these caveats in mind, transient
      elastography may be used as a diagnostic method to rule out liver cirrhosis (F4)
      in people with alcoholic liver disease when the pre-test probability is about 51%
      (range 15% to 79%). Transient elastography may also help in ruling out severe
      fibrosis (F3 or worse). Liver biopsy investigation remains an option if the
      certainty to rule in or rule out the stage of hepatic fibrosis or cirrhosis
      remains insufficient after a clinical follow-up or any other non-invasive test
      considered useful by the clinician.The proposed cut-off values for the different
      stages of hepatic fibrosis may be used in clinical practice, but caution is
      needed, as those values reported in this review are only the most common cut-off
      values used by the study authors. The best cut-off values for hepatic fibrosis in
      people with alcoholic liver disease could not be established yet.In order to
      diagnose correctly the stage of hepatic fibrosis in people with alcoholic liver
      disease using transient elastography assessment, the studies should consider a
      single aetiology. Hepatic fibrosis should be diagnosed with both transient
      elastography and liver biopsy and in this sequence, and transient elastography
      cut-off values should be pre-specified and validated. The time interval between
      the two investigations should not exceed three months, which is the interval
      mainly valid for people without cirrhosis, and assessment of results should be
      properly blinded. Only studies with low risk of bias, fulfilling the Standards
      for Reporting of Diagnostic Accuracy may answer the review question.

PMID- 25612183
TI  - Cardiac herniation through a pericardial defect after minimally invasive mitral
      valve surgery.
AB  - Minimally invasive mitral valve surgery has been increasingly performed because
      of its presumed advantages over traditional surgery performed through median
      sternotomy. Cardiac herniation is an extremely rare complication initially
      reported by Bettman and Tannenbaum in 1948. It is usually reported after blunt
      chest trauma or pneumonectomy, but can potentially occur after any minimally
      invasive surgery involving a pericardial incision. In this case report, we
      present 2 cases of cardiac herniation occurring after minimally invasive mitral
      valve surgery; the 2 cases had different surgical exposures and clinical
      presentations. Early diagnosis is crucial for a timely lifesaving definitive
      management. 

PMID- 25612184
TI  - Bone cement implantation syndrome during spinal surgery requiring cardiac
      surgery.
AB  - During a posterior segmental spinal fusion procedure, a 71-year-old woman
      developed cardiac and pulmonary embolism characterized by nonsustained
      ventricular tachycardia during cement injection, rapid and severe hypoxemia, and
      hemodynamic instability. Management included exploratory cardiotomy under
      cardiopulmonary bypass and removal of the emboli from the pulmonary vessels.
      Postoperative recovery was successful, and the patient was discharged without
      sequelae. We discuss the pathophysiology of bone cement implantation syndrome
      during spinal fusion, possible causative factors, and treatment alternatives. 

PMID- 25612185
TI  - Peripartum anesthetic management of a parturient with inherited factor v
      deficiency.
AB  - Inherited Factor V deficiency is a rare bleeding disorder. We describe the
      genetic analysis and anesthetic management of a parturient with severe Factor V
      deficiency who presented in spontaneous labor. Good hemostatic conditions were
      obtained with prophylactic fresh frozen plasma administration of 10 mL/kg.
      Detailed genetic analysis by next-generation sequencing identified several
      relevant mutations in the coding part of the Factor V (F5) gene in our patient,
      her parents, and the newborn. 

PMID- 25612186
TI  - Icodextrin causing glucose meter error and severe hypoglycemia after deceased
      donor renal transplant in a patient receiving continuous ambulatory peritoneal
      dialysis.
AB  - Hypoglycemia is a frequent problem encountered with diabetics and hospitalized
      patients. Although point-of-care glucose meters have revolutionized management,
      there are circumstances wherein glucose meter readings are inaccurate. One such
      example of glucose meter error occurred in a patient with end-stage renal disease
      receiving peritoneal dialysis who underwent renal transplantation. After surgery,
      the patient's laboratory testing reflected hypoglycemia, while point-of-care
      glucose meter testing indicated hyperglycemia. It is important to remember that
      the "gold standard" is the laboratory serum glucose test, and if a discrepancy
      from point-of-care results occurs, an investigation should be made to ascertain
      the reason. 

PMID- 25612187
TI  - Editorial comment: icodextrin causing glucose meter error and severe hypoglycemia
      after deceased donor renal transplant in a patient receiving continuous
      ambulatory peritoneal dialysis.

PMID- 25612188
TI  - From where will all the omega-3 fatty acids come?

PMID- 25612189
TI  - Endosulfan isomers and sulfate metabolite induced reproductive toxicity in
      Caenorhabditis elegans involves genotoxic response genes.
AB  - Endosulfan is enlisted as one of the persistent organic pollutants (POPs) and
      exists in the form of its alpha and beta isomers in the environment as well as in
      the form of endosulfan sulfate, a toxic metabolite. General endosulfan toxicity
      has been investigated in various organisms, but the effect of the isomers and
      sulfate metabolites on reproductive function is unclear. This study was aimed at
      studying the reproductive dysfunction induced by endosulfan isomers and its
      sulfate metabolite in Caenorhabditis elegans (C. elegans). We also determined a
      role for the DNA-damage-checkpoint gene hus-1. Compared to beta-endosulfan and
      its sulfate metabolite, alpha-endosulfan caused a dramatically higher level of
      germ cell apoptosis, which was regulated by DNA damage signal pathway. Both
      endosulfan isomers and the sulfate metabolite induced germ cell cycle arrest.
      Loss-of-function studies using hus-1, egl-1, and cep-1 mutants revealed that hus
      1 specifically influenced the fecundity, hatchability, and sexual ratio after
      endosulfan exposure. Our data provide clear evidence that the DNA-checkpoint gene
      hus-1 has an essential role in endosulfan-induced reproductive dysfunction and
      that alpha-endosulfan exhibited the highest reproductive toxicity among the
      different forms of endosulfan. 

PMID- 25612190
TI  - Unusual ferromagnetism in CoSi nanowires from internal and interfacial defects.
AB  - The diamagnetic semimetal CoSi presents unanticipated ferromagnetism as CoSi/SiO2
      nanowires (NWs). Using first-principles calculations, we offer physical insights
      into the origins of this unusual magnetism. Due to the distorted and dangling
      bonds near the NW surface with different bond lengths, the transition metal (Co)
      d-orbital electron spin up and spin down populations become asymmetric from the
      exchange interactions, providing the mechanism for some of the measured
      magnetization. However, the distorted and dangling bonds are clearly not the only
      factor contributing to the magnetization of the NWs. The transmission electron
      microscopy selected area electron diffraction analysis of the CoSi region
      suggested a superlattice structure existed in the cubic CoSi, and defects
      existing as ordered vacancies in the CoSi were present. The simulation's results
      for the Co moment in the CoSi NWs without these ordered vacancies, but
      incorporating the surface and internal spin moments, is only 0.1638 MU(B)/atom
      Co, which is a ~80% shortfall compared to the experimental value of 0.8400
      MU(B)/atom Co. When the effects of ordered vacancies are incorporated into the
      simulation, 0.7886 MU(B) per surface Co atom, a much better match with the
      experimental value (within ~6%), indicating that the internal ordered vacancies
      in the CoSi NWs are the dominant mechanism of ferromagnetism.

PMID- 25612192
TI  - Optically abrupt localized surface plasmon resonances in si nanowires by
      mitigation of carrier density gradients.
AB  - Spatial control of carrier density is critical for engineering and exploring the
      interactions of localized surface plasmon resonances (LSPRs) in nanoscale
      semiconductors. Here, we couple in situ infrared spectral response measurements
      and discrete dipole approximation (DDA) calculations to show the impact of
      axially graded carrier density profiles on the optical properties of mid-infrared
      LSPRs supported by Si nanowires synthesized by the vapor-liquid-solid technique.
      The region immediately adjacent to each intentionally encoded resonator (i.e.,
      doped segment) can exhibit residual carrier densities as high as 10(20) cm(-3),
      which strongly modifies both near- and far-field behavior. Lowering substrate
      temperature during the spacer segment growth reduces this residual carrier
      density and results in a spectral response that is indistinguishable from
      nanowires with ideal, atomically abrupt carrier density profiles. Our experiments
      have important implications for the control of near-field plasmonic phenomena in
      semiconductor nanowires, and demonstrate methods for determining and controlling
      axial dopant profile in these systems. 

PMID- 25612191
TI  - Sinonasal epithelial cell response to Staphylococcus aureus burden in chronic
      rhinosinusitis.
AB  - IMPORTANCE: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose
      and paranasal sinuses. Staphylococcus aureus is increasingly linked with CRS
      exacerbations. Little is known about how bacteria activate inflammatory pathways
      that contribute to CRS. OBJECTIVE: To develop an in vitro coculture system to
      explore how infection with S aureus stimulates innate immune responses of
      sinonasal epithelial cells (SNECs). DESIGN, SETTING, AND PARTICIPANTS: Sinonasal
      epithelial cells were collected from 13 patients during endoscopic sinus surgery
      and grown in culture at the air-liquid interface from July 2014 through December
      2014. INTERVENTIONS: Differentiated SNECs from control individuals, patients with
      CRS with nasal polyps (CRSwNPs), and patients with CRS without nasal polyps
      (CRSsNPs) were infected with S aureus at 3 different concentrations for 24 hours.
      MAIN OUTCOMES AND MEASURES: Growth of S aureus and viability of SNECs were
      measured. Expression of inflammatory markers and innate immune genes was measured
      by reverse transcription-polymerase chain reaction. Basal secretion of
      interleukin 8 was determined by enzyme-linked immunosorbent assay. RESULTS:
      Cultured SNECs from patients with CRSsNPs demonstrated a significant increase (P
      < .05) in expression of interleukin 8 (23-fold to 82-fold) and tumor necrosis
      factor (11-fold to 61-fold) at all the tested concentrations of S aureus. Control
      or CRSwNP SNECs demonstrated a significant increase (P < .05) in expression of
      interleukin 8 (47-fold and 50-fold, respectively) and tumor necrosis factor (106
      fold and 58-fold, respectively) at the higher inoculum of S aureus. Basal
      secretion of inflammatory markers correlated with expression changes. No
      significant changes in expression were observed for the helper T cell, subtype 2,
      inflammatory mediators tested. CONCLUSIONS AND RELEVANCE: In this study, we
      developed a model to study early innate immune-mediated changes in SNECs
      cocultured at an air-liquid interface with bacteria. We also demonstrated that
      bacterial burden can be detected by SNECs in the absence of adaptive immune
      mediated responses. The CRSsNP SNECs are more sensitive to S aureus burden than
      control or CRSwNP SNECs. Future studies will further develop this infection model
      and explore the SNEC innate immune response to bacteria.

PMID- 25612193
TI  - UV and sunlight driven photoligation of quantum dots: understanding the
      photochemical transformation of the ligands.
AB  - We have recently reported that photoinduced ligation of ZnS-overcoated quantum
      dots (QDs) offers a promising strategy to promote the phase transfer of these
      materials to polar and aqueous media using multidentate lipoic acid (LA)-modified
      ligands. In this study we investigate the importance of the underlying parameters
      that control this process, in particular, whether or not photoexcited QDs play a
      direct role in the photoinduced ligation. We find that irradiation of the ligand
      alone prior to mixing with hydrophobic QDs is sufficient to promote ligand
      exchange. Furthermore, photoligation onto QDs can also be carried out simply by
      using sunlight. Combining the use of Ellman's test with matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry, we probe the
      nature of the photochemical transformation of the ligands. We find that
      irradiation (using either a UV photoreactor or sunlight) alters the nature of the
      disulfide groups in the lipoic acid, yielding a different product mixture than
      what is observed for chemically reduced ligands. Irradiation of the ligand in
      solution generates a mixture of monomeric and oligomeric compounds. Ligation onto
      the QDs selectively favors oligomers, presumably due to their higher coordination
      onto the metal-rich QD surfaces. We also show that photoligation using mixed
      ligands allows the preparation of reactive nanocrystals. The resulting QDs are
      coupled to proteins and peptides and tested for cellular staining. This optically
      controlled ligation of QDs combined with the availability of a variety of
      multidentate and multifunctional LA-modified ligands open new opportunities for
      developing fluorescent platforms with great promises for use in imaging and
      sensor design. 

PMID- 25612194
TI  - Antitumor sulfonylhydrazines: design, structure-activity relationships,
      resistance mechanisms, and strategies for improving therapeutic utility.
AB  - 1,2-Bis(sulfonyl)-1-alkylhydrazines (BSHs) were conceived as more specific DNA
      guanine O-6 methylating and chloroethylating agents lacking many of the
      undesirable toxicophores contained in antitumor nitrosoureas. O(6)-Alkylguanine
      DNA alkyltransferase (MGMT) is the sole repair protein for O(6)-alkylguanine
      lesions in DNA and has been reported to be absent in 5-20% of most tumor types.
      Many BSHs exhibit highly selective cytotoxicity toward cells deficient in MGMT
      activity. The development of clinically useful MGMT assays should permit the
      identification of tumors with this vulnerability and allow for the preselection
      of patient subpopulations with a high probability of responding. The BSH system
      is highly versatile, permitting the synthesis of many prodrug types with the
      ability to incorporate an additional level of tumor-targeting due to preferential
      activation by tumor cells. Furthermore, it may be possible to expand the spectrum
      of activity of these agents to include tumors with MGMT activity by combining
      them with tumor-targeted MGMT inhibitors. 

PMID- 25612196
TI  - Cu-catalyzed aerobic oxidative esterification of acetophenones with alcohols to
      alpha-ketoesters.
AB  - Copper-catalyzed aerobic oxidative esterification of acetophenones with alcohols
      using molecular oxygen has been developed to form a broad range of alpha
      ketoesters in good yields. In addition to reporting scope and limitations of our
      new method, mechanism studies are reported that reveal that the carbonyl oxygen
      in the ester mainly originated from dioxygen. 

PMID- 25612195
TI  - Adenosine 2A receptors modulate reward behaviours for methamphetamine.
AB  - Addiction to methamphetamine (METH) is a global health problem for which there
      are no approved pharmacotherapies. The adenosine 2A (A2 A ) receptor presents a
      potential therapeutic target for METH abuse due to its modulatory effects on
      striatal dopamine and glutamate transmission. Notably, A2 A receptor signalling
      has been implicated in the rewarding effects of alcohol, cocaine and opiates;
      yet, the role of this receptor in METH consumption and seeking is essentially
      unknown. Therefore, the current study used A2 A knockout (KO) mice to assess the
      role of A2 A in behaviours relevant to METH addiction. METH conditioned place
      preference was absent in A2 A KO mice compared with wild-type (WT) littermates.
      Repeated METH treatment produced locomotor sensitization in both genotypes;
      however, sensitization was attenuated in A2 A KO mice in a dose-related manner.
      METH intravenous self-administration was intact in A2 A KO mice over a range of
      doses and schedules of reinforcement. However, the motivation to self-administer
      was reduced in A2 A KO mice. Regression analysis further supported the
      observation that the motivation to self-administer METH was reduced in A2 A KO
      mice even when self-administration was similar to WT mice. Sucrose self
      administration was also reduced in A2 A KO mice but only at higher schedules of
      reinforcement. Collectively, these data suggest that A2 A signalling is
      critically required to integrate rewarding and motivational properties of both
      METH and natural rewards. 

PMID- 25612197
TI  - Ultrasound-guided peripheral nerve blocks for ventricular shunt revision in
      children.
AB  - We describe using ultrasound-guided peripheral nerve blocks for postoperative
      pain control in 2 children undergoing ventricular shunt surgery. In the first
      patient undergoing ventriculo-peritoneal shunt revision, a combination of
      ultrasound-guided greater occipital nerve, superficial cervical plexus, and
      transversus abdominis plane blocks was used. In the second patient undergoing
      ventriculo-pleural shunt revision, a combination of ultrasound-guided greater
      occipital nerve, superficial cervical plexus, and intercostal blocks was used.
      Both patients, who underwent multiple revisions during their hospitalizations,
      showed decreased analgesic requirements after regional anesthesia. Our experience
      suggests this combined block technique may provide beneficial postoperative
      analgesia for patients undergoing shunt revision. 

PMID- 25612198
TI  - Editorial comment: ultrasound-guided peripheral nerve blocks for ventricular
      shunt revision in children.

PMID- 25612199
TI  - Conservative treatment of an epidural abscess after thoracic epidural
      catheterization.
AB  - We describe a case of a thoracic epidural abscess after epidural catheter
      insertion in a patient undergoing lobar segmentectomy. The patient described a
      "pulsatile" back pain the sixth day after surgery, and purulent material at the
      entry site of the catheter was observed. The image of the nuclear magnetic
      resonance confirmed an epidural abscess that was treated conservatively with
      antibiotics after a consensus decision among neurosurgery, infectious diseases an
      anesthesia services. The abscess was reabsorbed completely with no sequelae. 

PMID- 25612200
TI  - Awake microlaryngoscopy and serial balloon dilation in a third trimester
      multigravida with subglottic tracheal stenosis: anesthetic implications.
AB  - Tracheal stenosis in pregnancy is a relatively rare occurrence and there are
      limited data regarding the perioperative management of these patients. Various
      surgical treatment options are available to include open repair, long-term
      tracheostomy, or endoscopic repair (rigid versus balloon dilation). We report the
      case of a woman in her third trimester of pregnancy, with known recurrent and
      worsening history of subglottic tracheal stenosis, who underwent awake
      microlaryngoscopy with potassium titanyl phosphate laser radial incision and
      serial tracheal balloon dilation under topical anesthesia with sedation. We
      further discuss her perioperative multidisciplinary management. 

PMID- 25612201
TI  - Treatment of posttraumatic supraorbital neuralgia using pulsed radiofrequency
      ablation.
AB  - Supraorbital neuralgia, although an uncommon disorder, is the most frequent
      extracranial neuralgia of the trigeminal nerve. There are several small case
      studies reporting treatment outcomes offered by various types of medical
      management and even surgical treatment. We present the case of a 36-year-old
      female patient who developed debilitating supraorbital neuralgia after a
      concussion and unsuccessful medical management. She underwent 2 treatments with
      pulsed radiofrequency ablation that resulted in significant relief, allowing her
      to return to work and normal daily activities. Pulsed radiofrequency ablation
      offers a nonsurgical option for patients with this painful disorder. 

PMID- 25612202
TI  - Mask induction despite circuit obstruction: an unrecognized hazard of relying on
      automated machine check technology.
AB  - Various equipment malfunctions of anesthesia gas delivery systems have been
      previously reported. Our profession increasingly uses technology as a means to
      prevent these errors. We report a case of a near-total anesthesia circuit
      obstruction that went undetected before the induction of anesthesia despite the
      use of automated machine check technology. This case highlights that automated
      machine check modules can fail to detect severe equipment failure and
      demonstrates how, even in this era of expanding technology, manual checks still
      remain essential components of safe care. 

PMID- 25612203
TI  - Editorial comment: mask induction despite circuit obstruction: an unrecognized
      hazard of relying on automated machine check technology.

PMID- 25612204
TI  - Bronchospasm induced by ethanol injection for a craniofacial venous malformation.
AB  - Ethanol sclerotherapy is a first-line treatment for low-flow vascular
      malformations. Although many complications of ethanol sclerotherapy have been
      described in the literature, bronchospasm is uncommon. We present a case of a
      patient in whom bronchospasm was precipitated by injection of ethanol during
      percutaneous sclerotherapy for craniofacial venous malformations that occurred
      during general anesthesia. The evidence for ethanol-induced bronchospasm is
      discussed. 

PMID- 25612205
TI  - Anesthetic Challenges in an Adult with Mucopolysaccharidosis Type VI.
AB  - The mucopolysaccharidoses are a group of lysosomal storage diseases with many
      skeletal and airway features that pose a challenge to anesthetists. We present
      the anesthetic management of a woman with mucopolysaccharidosis type VI
      undergoing cervical spine surgery and review the perioperative issues that may
      arise with this disease. 

PMID- 25612206
TI  - Ultrasound-guided transversus abdominis plane/genitofemoral blocks for a patient
      receiving extracorporeal life support.
AB  - Extracorporeal life support may be used in patients with refractory cardiogenic
      shock. The femoral venoarterial route can be used for implanting cannulae in
      patients who are hemodynamically unstable. Here we describe the use of an
      ultrasound-guided transversus abdominis plane block supplemented with the femoral
      component of the genitofemoral nerve as the anesthesia technique for peripheral
      cannulation of the femoral vessels in a patient with severe acute heart failure
      after myocardial infarction with ST-segment elevation. The procedure was
      performed using 40 mL of a 50:50 mixture of 0.5% levobupivacaine and 2% lidocaine
      (30 mL for transversus abdominis plane and 10 mL for genitofemoral block)
      associated with low-dose remifentanil infusion during spontaneous breathing. A
      left ventricular assist device was successfully implanted 4 days later. 

PMID- 25612207
TI  - Gas phase chemistry of N-benzylbenzamides with silver(I) cations:
      characterization of benzylsilver cation.
AB  - The benzylsilver cation which emerges from the collisional dissociation of
      silver(I)-N-benzylbenzamide complexes was characterized by deuterium-labeling
      experiments, theoretical calculations, breakdown curves and substituent effects.
      The nucleophilic attack of the carbonyl oxygen on an alpha-hydrogen results in
      the generation of the benzylsilver cation, which is competitive to the AgH loss
      with the alpha-hydrogen.

PMID- 25612208
TI  - Reference values for oral iron absorption of bivalent iron in healthy volunteers.
AB  - BACKROUND: It is a challenge to establish the cause of iron deficiency in the
      absence of obvious reasons. There has been no prospectively validated oral iron
      absorption test (OIAT) that could confidently confirm or exclude iron
      malabsorption. The aim, therefore, was the establishment of an OIAT with defining
      reference values of plasma iron in healthy volunteers. METHODS: We included 49
      healthy volunteers who received 200 mg of bivalent ferrous fumarate in fasting
      condition and measured plasma iron after 2 and 4 hours as well as after 3 and 5
      days. After a wash-out phase, 23 healthy volunteers proceeded to receive
      trivalent iron hydroxide polymaltose in fasting condition, and 11 participants
      were tested without iron. RESULTS: Reference values of absolute and relative
      plasma iron after oral iron ingestion could be established. There was a
      significant increase of plasma iron after bivalent iron intake within 4 hours
      after ingestion (absolute increase after 4h: from initially 17 +/- 4 umol/l to 35
      +/- 12 umol/l in females and from 21 +/- 7 umol/l to 33 +/- 11 umol/l in males,
      relative plasma iron concentration (defined reference: 1.0) after 4 h: 2.1 +/-
      0.7 in females and 1.7 +/- 0.6 in males). There was no relevant increase with
      trivalent iron nor without iron. Relative iron increase correlates to iron
      storage. In general, females had lower ferritin levels and thus higher increases
      of plasma iron. CONCLUSION: An OIAT in healthy volunteers could be established.
      Its prospective validation using bivalent iron in iron deficiency is desirable.

PMID- 25612209
TI  - Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk
      factors for psychiatric disorders.
AB  - Nitric oxide (NO) is a gaseous transmitter produced by nitric oxide synthases
      (NOSs). The neuronal isoform (NOS-I, encoded by NOS1) is the main source of NO in
      the central nervous system (CNS). Animal studies suggest that nitrinergic
      dysregulation may lead to behavioral abnormalities. Unfortunately, the large
      number of animal studies is not adequately reflected by publications concerning
      humans. These include post-mortem studies, determination of biomarkers, and
      genetic association studies. Here, we review the evidence for the role of NO in
      psychiatric disorders by focusing on the human NOS1 gene as well as biomarker
      studies. Owing to the complex regulation of NOS1 and the varying function of NOS
      I in different brain regions, no simple, unidirectional association is expected.
      Rather, the 'where, when and how much' of NO formation is decisive. Present data,
      although still preliminary and partially conflicting, suggest that genetically
      driven reduced NO signaling in the prefrontal cortex is associated with
      schizophrenia and cognition. Both NOS1 and its interaction partner NOS1AP have a
      role therein. Also, reduced NOS1 expression in the striatum determined by a
      length polymorphism in a NOS1 promoter (NOS1 ex1f-VNTR) goes along with a variety
      of impulsive behaviors. An association of NOS1 with mood disorders, suggested by
      animal models, is less clear on the genetic level; however, NO metabolites in
      blood may serve as biomarkers for major depression and bipolar disorder. As the
      nitrinergic system comprises a relevant target for pharmacological interventions,
      further studies are warranted not only to elucidate the pathophysiology of mental
      disorders, but also to evaluate NO function as a biomarker. 

PMID- 25612210
TI  - Correction to Ion-exchange mechanism of layered transition-metal oxides: case
      study of LiNi0.5Mn0.5O2.

PMID- 25612211
TI  - Nosewitness identification: effects of negative emotion.
AB  - Every individual has a unique body odor (BO), similar to a fingerprint. In
      forensic research, identification of culprit BOs has been performed by trained
      dogs, but not by humans. We introduce the concept of nosewitness identification
      and present the first experimental results on BO memory in witness situations
      involving violent crimes. Two experiments indicated that BO associated with male
      characters in authentic videos could later be identified in BO lineup tests well
      above chance. Moreover, culprit BO in emotional crime videos could be identified
      considerably better than the BO of a male person in neutral videos. This
      indicates that nosewitness identification benefits from emotional encoding.
      Altogether, the study testifies to the virtue of body odor as a cue to identify
      individuals observed under negative emotion. 

PMID- 25612213
TI  - Two-dimensional NiCo2O4 nanosheet-coated three-dimensional graphene networks for
      high-rate, long-cycle-life supercapacitors.
AB  - We report the synthesis of two-dimensional (2D) NiCo2O4 nanosheet-coated three
      dimensional graphene network (3DGN), which is then used as an electrode for high
      rate, long-cycle-life supercapacitors. Using the 3DGN and nanoporous nanosheets,
      an ultrahigh specific capacitance (2173 F g(-1) at 6 A g(-1)), excellent rate
      capability (954 F g(-1) at 200 A g(-1)) and superior long-term cycling
      performance (94% capacitance retention after 14,000 cycles at 100 A g(-1)) are
      achieved.

PMID- 25612212
TI  - Negative evaluation bias for positive self-referential information in borderline
      personality disorder.
AB  - Previous research has suggested that patients meeting criteria for borderline
      personality disorder (BPD) display altered self-related information processing.
      However, experimental studies on dysfunctional self-referential information
      processing in BPD are rare. In this study, BPD patients (N = 30) and healthy
      control participants (N = 30) judged positive, neutral, and negative words in
      terms of emotional valence. Referential processing was manipulated by a preceding
      self-referential pronoun, an other-referential pronoun, or no referential
      context. Subsequently, patients and participants completed a free recall and
      recognition task. BPD patients judged positive and neutral words as more negative
      than healthy control participants when the words had self-reference or no
      reference. In BPD patients, these biases were significantly correlated with self
      reported attributional style, particularly for negative events, but unrelated to
      measures of depressive mood. However, BPD patients did not differ from healthy
      control participants in a subsequent free recall task and a recognition task. Our
      findings point to a negative evaluation bias for positive, self-referential
      information in BPD. This bias did not affect the storage of information in
      memory, but may be related to self-attributions of negative events in everyday
      life in BPD. 

PMID- 25612214
TI  - International Journal of Environmental Research and Public Health Best Paper
      Award 2015.

PMID- 25612215
TI  - Sarcopenia as a prognostic biomarker of advanced urothelial carcinoma.
AB  - OBJECTIVES: Sarcopenia, a novel concept reflecting the degenerative loss of
      skeletal muscle mass, is an objective indicator of cancer cachexia. We
      investigated its role as a prognostic biomarker in advanced urothelial carcinoma
      (UC) patients. METHODS: This retrospective study consisted of 88 UC patients with
      cT4 and/or metastases to lymph nodes/distant organs. Skeletal muscle index (SMI),
      an indicator of whole-body muscle mass, was measured from computed tomography
      (CT) images at the diagnosis. Sarcopenia was defined as SMIs of <43 cm(2)/m(2)
      for males with body mass index (BMI) <25 cm(2)/m(2), <53 cm(2)/m(2) for males
      with BMI >= 25 cm(2)/m(2), and <41 cm(2)/m(2) for females. Predictors of overall
      survival (OS) were examined using Cox proportional hazard models. RESULTS: Sixty
      seven patients (76%) died during the median follow-up of 13 months. The median OS
      rate was 13 months. Multivariate analysis revealed that SMI was a significant and
      independent predictor of shorter OS (hazard ratio (HR) 0.90, P <0.001). In the
      present cohort, 53 (60%) were diagnosed with sarcopenia. The median OS rates were
      11 and 31 months for sarcopenic and non-sarcopenic patients, respectively (P
      <0.001). On multivariate analysis, sarcopenia was a significant and independent
      predictor of shorter OS (HR 3.36, P <0.001), along with higher C-reactive protein
      (CRP) (P = 0.001), upper urinary tract cancer (P = 0.007), higher lactate
      dehydrogenase (LDH) (P = 0.047), and higher alkaline phosphatase (ALP) (P =
      0.048). CONCLUSION: Sarcopenia, which is readily evaluated on routine CT scans,
      is a useful prognostic biomarker of advanced UC. Non-sarcopenic patients can
      expect long-term survival. Evaluating sarcopenia can be helpful for decision
      making processes in the management of advanced UC patients.

PMID- 25612216
TI  - Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to
      severe mixed major depressive episodes: a post hoc analysis.
AB  - OBJECTIVE: Depression is the predominant psychosocial and suicide burden in
      bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar
      depression. METHODS: This post hoc subgroup analysis of data pooled from two 3
      week, randomized, placebo- and olanzapine-controlled trials (December 2004-April
      2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of
      patients meeting criteria for moderate-to-severe mixed major depressive episodes,
      defined using DSM-IV-TR criteria for mixed episodes (mania and major depression
      simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS)
      total score >= 20. RESULTS: Decreases in MADRS scores (least squares mean [SE]),
      the a priori primary outcome, were significantly greater in the asenapine group
      than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89];
      P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (
      10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine
      were significantly greater than with olanzapine from baseline to day 7 (-6.26
      [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were
      greater with asenapine than with placebo or olanzapine at all time points
      assessed. A significantly greater reduction from baseline to day 21 in the Short
      Form-36 mental component summary score was observed with asenapine, but not
      olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was
      generally well tolerated. CONCLUSIONS: These data provide support for the
      potential efficacy of asenapine in mixed major depressive episodes; however,
      these data cannot be linearly extrapolated to nonmixed major depression.

PMID- 25612217
TI  - A mixed-methods approach to understanding barriers to postpartum retention in
      care among low-income, HIV-infected women.
AB  - Optimal retention in HIV care postpartum is necessary to benefit the health and
      wellbeing of mothers and their infants. However, postpartum retention in HIV care
      among low-income women is suboptimal, particularly in the Southern United States.
      A mixed-methods study was conducted to identify factors associated with
      postpartum retention in care among HIV-infected women. Participants (n=35) were
      recruited during pregnancy at two county clinics and completed self-report
      demographic and psychosocial surveys. Twenty-two women who returned for a
      postpartum appointment completed a semi-structured interview about lifestyle
      factors and retention in care. Of the participants enrolled at baseline, 71.4%
      completed a follow-up with an obstetrician (OB), while 57.1% completed a follow
      up with a primary care physician (PCP). High CD4 count at delivery, low viral
      load at baseline, low levels of depression, high interpersonal social support,
      and fewer other children were significantly associated with completion of
      postpartum follow-up. Barriers and facilitators to retention identified during
      qualitative interviews included competing responsibilities for time, lack of
      social support outside of immediate family members, limited transportation
      access, experiences of institutionalized stigma, knowledge about the benefits of
      adherence, and strong relationships with healthcare providers. OB and PCP follow
      up postpartum was suboptimal in this sample. Findings underscore the importance
      of addressing depressive symptoms, social support, viral suppression, competing
      responsibilities for time, institutionalized stigma, and transportation issues in
      order to reduce the barriers that inhibit women from seeking postpartum HIV care.

PMID- 25612218
TI  - Ascending control of arousal and motivation: role of nucleus incertus and its
      peptide neuromodulators in behavioural responses to stress.
AB  - Arousal is a process that involves the activation of ascending neural pathways
      originating in the rostral pons that project to the forebrain through the
      midbrain reticular formation to promote the activation of key cortical, thalamic,
      hypothalamic and limbic centres. Established modulators of arousal include the
      cholinergic, serotonergic, noradrenergic and dopaminergic networks originating in
      the pons and midbrain. Recent data indicate that a population of largely
      GABAergic projection neurones located in the nucleus incertus (NI) are also
      involved in arousal and motivational processes. The NI has prominent efferent
      connections with distinct hypothalamic, amygdalar and thalamic nuclei, in
      addition to dense projections to key brain regions associated with the generation
      and pacing of hippocampal activity. The NI receives strong inputs from the
      prefrontal cortex, lateral habenula and the interpeduncular and median raphe
      nuclei, suggesting it is highly integrated in circuits regulating higher
      cognitive behaviours (hippocampal theta rhythm) and emotion. Anatomical and
      functional studies have revealed that the NI is a rich source of multiple peptide
      neuromodulators, including relaxin-3, and may mediate extra-hypothalamic effects
      of the stress hormone corticotrophin-releasing factor, as well as other key
      modulators such as orexins and oxytocin. This review provides an overview of
      earlier studies and highlights more recent research that implicates this neural
      network in the integration of arousal and motivated behaviours and has begun to
      identify the associated mechanisms. Future research that should help to better
      clarify the connectivity and function of the NI in major experimental species and
      humans is also discussed. 

PMID- 25612219
TI  - Graphene-supported iron-based nanoparticles encapsulated in nitrogen-doped carbon
      as a synergistic catalyst for hydrogen evolution and oxygen reduction reactions.
AB  - Electrolyzers and fuel cells have been extensively investigated as promising
      solutions for renewable energy storage and conversion. Hydrogen evolution
      reaction (HER) and oxygen reduction reaction (ORR) are important electrocatalytic
      processes in electrolyzers and fuel cells. Exploring efficient non-precious metal
      catalysts for HER and ORR in acidic medium remains a great challenge. Herein, we
      report that graphene-supported iron-based nanoparticles encapsulated in a
      nitrogen-doped carbon (Fe@N-C) hybrid material acts as an efficient HER and ORR
      catalyst. The hybrid material was synthesized by pyrolysis of graphene oxide and
      ammonia ferric citrate followed by acid-leaching. During the pyrolysis, nitrogen
      was doped into a graphene lattice, and the carbon nanoshell grown on graphene
      effectively suppressed the stacking of graphene sheets, exposing more active
      sites to reactants. The hybrid material showed higher electrocatalytic activities
      than graphene sheets or Fe@N-C alone, which is probably attributed to the
      synergetic role of nitrogen-doped graphene and Fe@N-C towards the
      electrocatalytic reactions. 

PMID- 25612220
TI  - Re.: Is screening for congenital colour vision deficiency in school students
      worthwhile? A review.

PMID- 25612221
TI  - Commercial Origanum compactum Benth. and Cinnamomum zeylanicum Blume essential
      oils against natural mycoflora in Valencia rice.
AB  - Chemical composition of commercial Origanum compactum and Cinnamomum zeylanicum
      essential oils and the antifungal activity against pathogenic fungi isolated from
      Mediterranean rice grains have been investigated. Sixty-one compounds accounting
      for more than 99.5% of the total essential oil were identified by using gas
      chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Carvacrol
      (43.26%), thymol (21.64%) and their biogenetic precursors p-cymene (13.95%) and
      gamma-terpinene (11.28%) were the main compounds in oregano essential oil, while
      the phenylpropanoids, eugenol (62.75%), eugenol acetate (16.36%) and (E)-cinnamyl
      acetate (6.65%) were found in cinnamon essential oil. Both essential oils at 300
      MUg/mL showed antifungal activity against all tested strains. O. compactum
      essential oil showed the best antifungal activity towards Fusarium species and
      Bipolaris oryzae with a total inhibition of the mycelial growth. In inoculated
      rice grains at lower doses (100 and 200 MUg/mL) significantly reduced the fungal
      infection, so O. compactum essential oil could be used as ecofriendly
      preservative for field and stored Valencia rice.

PMID- 25612222
TI  - An integrative review of experiences of patients with rheumatoid arthritis.
AB  - AIM: To provide an overview of evidence on the experiences and needs of adults
      living with rheumatoid arthritis (RA). BACKGROUND: Many research have studied the
      impact of RA on one's quality of life, but no reviews have examined the overall
      experiences of patients living with RA. METHODS: An integrative review was
      performed to synthesize the experiences and/or needs of adult patients with RA
      based on articles retrieved from databases of CINAHL, Scopus, PubMed, PsycINFO
      and Web of Science, and published between January 2003 and March 2014 in English.
      RESULTS: A total of 38 studies were reviewed. RA has adverse effects on patients'
      quality of life due to its negative impacts in their physical and psychosocial
      aspects of health. Patients with RA cope with these impacts using various methods
      and are frequent users of healthcare services. However, few studies have
      evaluated patients' further needs in coping or the effectiveness of their coping
      mechanisms, and patients' experiences with health care. CONCLUSION: This review
      provides evidence for healthcare professionals to gain a better understanding of
      RA patients' experiences and needs. Future studies can explore interventions that
      will enhance the quality of current healthcare practices and ultimately improve
      patients' quality of life. IMPLICATIONS FOR NURSING AND HEALTH POLICY:
      Establishing a positive healthcare professional-patient relationship is crucial
      and healthcare professionals are in a position to provide greater informational
      and emotional support to patients. Policy makers and healthcare organizations
      need to look into ways to enhance the healthcare services to better suit RA
      patients' needs.

PMID- 25612223
TI  - Oxidation of Fe(II)-EDTA by nitrite and by two nitrate-reducing Fe(II)-oxidizing
      Acidovorax strains.
AB  - The enzymatic oxidation of Fe(II) by nitrate-reducing bacteria was first
      suggested about two decades ago. It has since been found that most strains are
      mixotrophic and need an additional organic co-substrate for complete and
      prolonged Fe(II) oxidation. Research during the last few years has tried to
      determine to what extent the observed Fe(II) oxidation is driven enzymatically,
      or abiotically by nitrite produced during heterotrophic denitrification. A recent
      study reported that nitrite was not able to oxidize Fe(II)-EDTA abiotically, but
      the addition of the mixotrophic nitrate-reducing Fe(II)-oxidizer, Acidovorax sp.
      strain 2AN, led to Fe(II) oxidation (Chakraborty & Picardal, 2013). This, along
      with other results of that study, was used to argue that Fe(II) oxidation in
      strain 2AN was enzymatically catalyzed. However, the absence of abiotic Fe(II)
      EDTA oxidation by nitrite reported in that study contrasts with previously
      published data. We have repeated the abiotic and biotic experiments and observed
      rapid abiotic oxidation of Fe(II)-EDTA by nitrite, resulting in the formation of
      Fe(III)-EDTA and the green Fe(II)-EDTA-NO complex. Additionally, we found that
      cultivating the Acidovorax strains BoFeN1 and 2AN with 10 mM nitrate, 5 mm
      acetate, and approximately 10 mM Fe(II)-EDTA resulted only in incomplete Fe(II)
      EDTA oxidation of 47-71%. Cultures of strain BoFeN1 turned green (due to the
      presence of Fe(II)-EDTA-NO) and the green color persisted over the course of the
      experiments, whereas strain 2AN was able to further oxidize the Fe(II)-EDTA-NO
      complex. Our work shows that the two used Acidovorax strains behave very
      differently in their ability to deal with toxic effects of Fe-EDTA species and
      the further reduction of the Fe(II)-EDTA-NO nitrosyl complex. Although the
      enzymatic oxidation of Fe(II) cannot be ruled out, this study underlines the
      importance of nitrite in nitrate-reducing Fe(II)- and Fe(II)-EDTA-oxidizing
      cultures and demonstrates that Fe(II)-EDTA cannot be used to demonstrate
      unequivocally the enzymatic oxidation of Fe(II) by mixotrophic Fe(II)-oxidizers.

PMID- 25612224
TI  - Changes in bile acids, FGF-19 and sterol absorption in response to bile salt
      hydrolase active L. reuteri NCIMB 30242.
AB  - The size and composition of the circulating bile acid (BA) pool are important
      factors in regulating the human gut microbiota. Disrupted regulation of BA
      metabolism is implicated in several chronic diseases. Bile salt hydrolase (BSH)
      active Lactobacillus reuteri NCIMB 30242, previously shown to decrease LDL
      cholesterol and increase circulating BA, was investigated for its dose response
      effect on BA profile in a pilot clinical study. Ten otherwise healthy
      hypercholesterolemic adults, recruited from a clinical trial site in London, ON,
      were randomized to consume delayed release or standard release capsules
      containing L. reuteri NCIMB 30242 in escalating dose over 4 weeks. In another
      aspect, 4 healthy normocholesterolemic subjects with LDL-C below 3.4 mmol/l
      received delayed release L. reuteri NCIMB 30242 at a constant dose over 4 weeks.
      The primary outcome measure was the change in plasma BA profile over the
      intervention period. Additional outcomes included circulating fibroblast growth
      factor (FGF)-19, plant sterols and LDL-cholesterol as well as fecal microbiota
      and bsh gene presence. After one week of intervention subjects receiving delayed
      release L. reuteri NCIMB 30242 increased total BA by 1.13 +/- 0.67 MUmol/l (P =
      0.02), conjugated BA by 0.67 +/- 0.39 MUmol/l (P = 0.02) and unconjugated BA by
      0.46 +/- 0.43 MUmol/l (P = 0.07), which represented a greater than 2-fold change
      relative to baseline. Increases in BA were largely maintained post-week 1 and
      were generally correlated with FGF-19 and inversely correlated with plant
      sterols. This is the first clinical support showing that a BSH-active probiotic
      can significantly and rapidly influence BA metabolism and may prove useful in
      chronic diseases beyond hypercholesterolemia. 

PMID- 25612226
TI  - Obesity and other aspects of hypertension.

PMID- 25612225
TI  - Discovery of mosquito saliva microRNAs during CHIKV infection.
AB  - Mosquito borne pathogens are transmitted to humans via saliva during blood
      feeding. Mosquito saliva is a complex concoction of many secretory factors that
      modulate the feeding foci to enhance pathogen infection and establishment.
      Multiple salivary proteins/factors have been identified/characterized that
      enhance pathogen infection. Here, we describe, for the first time, the
      identification of exogenous microRNAs from mosquito saliva. MicroRNAs are short,
      18-24 nucleotide, non-coding RNAs that regulate gene expression, and are
      generally intracellular. However, circulating miRNAs have been described from
      serum and saliva of humans. Exogenous miRNAs have not been reported from
      hematophagous arthropod saliva. We sought to identify miRNAs in the mosquito
      saliva and their role in Chikungunya virus (CHIKV) infection. Next generation
      sequencing was utilized to identify 103 exogenous miRNAs in mosquito saliva of
      which 31 miRNAs were previously unidentified and were designated novel. Several
      miRNAs that we have identified are expressed only in the CHIKV infected
      mosquitoes. Five of the saliva miRNAs were tested for their potential to
      regulated CHIKV infection, and our results demonstrate their functional role in
      the transmission and establishment of infection during blood feeding on the host.

PMID- 25612227
TI  - Trust in African Americans' Healthcare Experiences.
AB  - PURPOSE: The purpose of the study is to clarify the concept of trust, identify
      its defining attributes, antecedents, and consequences, and apply to the
      healthcare experiences of African Americans. BACKGROUND: For African Americans,
      mistrust in the healthcare system is the result of unequal treatment that began
      in slavery. Fear and negative experiences engender a reluctance to trust
      healthcare providers, which contributes to health disparities. DESIGN: Walker and
      Avant's method of concept analysis was used to clarify the concept of trust. The
      concept was applied to African Americans' healthcare experiences with discussion
      of opportunities for trust building. DATA SOURCE: Data support for concept
      development was done using Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), Medline, and online reference sources. REVIEW METHODS:
      Literature review was guided by using the keyword trust. Further contextual
      explication was done by adding a review of literature from sociology and history
      regarding the evolution of African American mistrust of the U.S. healthcare
      system. RESULTS: The defining attributes of trust are dependence, willingness,
      and met expectations. Antecedents to trust include a need requiring the help of
      another and prior knowledge or experience. The consequence of trust is an
      evaluation of the congruence between expected and actual behaviors of the trusted
      person or thing. Literature review of the African American culture adds a dynamic
      aspect for nurses to consider when developing relationships in minority
      communities. CONCLUSION: Trust is the willingness to enter a dependent
      relationship to have the needs addressed, and is maintained by met expectations.
      Rebuilding trusting relationships between providers and African American patients
      is a vital step toward reducing health disparities. Murray.

PMID- 25612229
TI  - Outpatient Clinic for Health Education: Contribution to Self-Management and Self
      Care for People With Heart Failure.
AB  - OBJECTIVE: To report the experience of an outpatient nursing education clinic
      caring for people with chronic heart failure. EXPERIENCE REPORT: In this service,
      qualified "listening," recreational educational actions about the disease and its
      treatment are conducted, based on the interventions from the Nursing
      Interventions Classification (NIC), as well as the evaluation of self-care
      behaviors with the outcomes from the Nursing Outcomes Classification (NOC). This
      article describes the practice of health education activities and the use of
      NANDA-I-NIC-NOC in a nursing clinic. CONCLUSION: The outpatient clinic supports
      client learning about the treatment of disease and stimulates self-control of
      health behaviors. IMPLICATIONS FOR NURSING PRACTICE: This experience report will
      guide nurses in the establishment of outpatient nursing education clinics for
      different populations of patients with chronic health conditions.

PMID- 25612228
TI  - Differential Effect of Modified Medical Research Council Dyspnea, COPD Assessment
      Test, and Clinical COPD Questionnaire for Symptoms Evaluation Within the New GOLD
      Staging and Mortality in COPD.
AB  - OBJECTIVE: The modified Medical Research Council (mMRC) dyspnea, the COPD
      Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been
      interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung
      Disease) for assessing symptoms in patients with COPD. However, there are no data
      on the prognostic value of these tools in terms of mortality. We endeavored to
      evaluate the prognostic value of the CAT and CCQ scores and compare them with
      mMRC dyspnea. METHODS: We analyzed the ability of these tests to predict
      mortality in an observational cohort of 768 patients with COPD (82% men; FEV1,
      60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter
      observational Spanish cohort, who were monitored annually for a mean follow-up
      time of 38 months. RESULTS: Subjects who died (n = 73; 9.5%) had higher CAT (14
      vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P
      < .001) than survivors. Receiver operating characteristic analysis showed that
      higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality
      (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores >= 17
      and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores >= 2
      to predict all-cause mortality. CONCLUSIONS: The CAT and the CCQ have similar
      ability for predicting all-cause mortality in patients with COPD, but were
      inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores
      based on mortality risk that could be useful for the new GOLD grading
      classification. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01122758; URL:
      www.clinicaltrials.gov.

PMID- 25612230
TI  - High-yield and high-purity isolation of hepatic stellate cells from normal and
      fibrotic mouse livers.
AB  - Hepatic stellate cells (HSCs) have been identified as the main fibrogenic cell
      type in the liver. Hence, efforts to understand hepatic fibrogenesis and to
      develop treatment strategies have focused on this cell type. HSC isolation,
      originally developed in rats, has subsequently been adapted to mice, thus
      allowing the study of fibrogenesis by genetic approaches in transgenic mice.
      However, mouse HSC isolation is commonly hampered by low yield and purity. Here
      we present an easy-to-perform protocol for high-purity and high-yield isolation
      of quiescent and activated HSCs in mice, based on retrograde pronase-collagenase
      perfusion of the liver and subsequent density-gradient centrifugation. We
      describe an optional add-on protocol for ultrapure HSC isolation from normal and
      fibrotic livers via subsequent flow cytometric sorting, thus providing a
      validated method to determine gene expression changes during HSC activation
      devoid of cell culture artifacts or contamination with other cells. The described
      isolation procedure takes ~4 h to complete. 

PMID- 25612232
TI  - The Na(+)/HCO3(-) Co-Transporter SLC4A4 Plays a Role in Growth and Migration of
      Colon and Breast Cancer Cells.
AB  - The hypoxic and acidic tumor environment necessitates intracellular pH (pHi)
      regulation for tumor progression. Carbonic anhydrase IX (CA IX; hypoxia-induced)
      is known to facilitate CO2 export and generate HCO3(-) in the extracellular tumor
      space. It has been proposed that HCO3(-) is re-captured by the cell to maintain
      an alkaline pHi . A diverse range of HCO3(-) transporters, coupled with a lack of
      a clear over-expression in cancers have limited molecular identification of this
      cellular process. Here, we report that hypoxia induces the Na(+)/HCO3(-) co
      transporter (NBCe1) SLC4A4 mRNA expression exclusively in the LS174 colon
      adenocarcinoma cell line in a HIF1alpha dependent manner. HCO3(-) dependent pHi
      recovery observations revealed the predominant use of an NBC mechanism suggesting
      that reversal of a Cl(-)/HCO3(-) exchanger is not utilized for tumor cell pHi
      regulation. Knockdown of SLC4A4 via shRNA reduced cell proliferation and
      increased mortality during external acidosis and spheroid growth. pHi recovery
      from acidosis was partially reduced with knockdown of SLC4A4. In MDA-MB-231
      breast cancer cells expressing high levels of SLC4A4 compared to LS174 cells,
      SLC4A4 knockdown had a strong impact on cell proliferation, migration, and
      invasion. SLC4A4 knockdown also altered expression of other proteins including CA
      IX. Furthermore the Na(+)/HCO3(-) dependent pHi recovery from acidosis was
      reduced with SLC4A4 knockdown in MDA-MB-231 cells. Combined our results indicate
      that SLC4A4 contributes to the HCO3(-) transport and tumor cell phenotype. This
      study complements the on-going molecular characterization of the HCO3(-) re
      uptake mechanism in other tumor cells for future strategies targeting these
      potentially important drug targets.

PMID- 25612231
TI  - Palladium-based mass tag cell barcoding with a doublet-filtering scheme and
      single-cell deconvolution algorithm.
AB  - Mass-tag cell barcoding (MCB) labels individual cell samples with unique
      combinatorial barcodes, after which they are pooled for processing and
      measurement as a single multiplexed sample. The MCB method eliminates variability
      between samples in antibody staining and instrument sensitivity, reduces antibody
      consumption and shortens instrument measurement time. Here we present an
      optimized MCB protocol. The use of palladium-based labeling reagents expands the
      number of measurement channels available for mass cytometry and reduces
      interference with lanthanide-based antibody measurement. An error-detecting
      combinatorial barcoding scheme allows cell doublets to be identified and removed
      from the analysis. A debarcoding algorithm that is single cell-based rather than
      population-based improves the accuracy and efficiency of sample deconvolution.
      This debarcoding algorithm has been packaged into software that allows rapid and
      unbiased sample deconvolution. The MCB procedure takes 3-4 h, not including
      sample acquisition time of ~1 h per million cells. 

PMID- 25612233
TI  - Approaches to laparoscopic liver resection: a meta-analysis of the role of hand
      assisted laparoscopic surgery and the hybrid technique.
AB  - Laparoscopic liver resection has been established as a safe and feasible
      treatment option. Surgical approaches include pure laparoscopy, hand-assisted
      laparoscopy (HALS), and the hybrid technique. The role of these three approaches,
      and their superiority over open laparotomy, is not yet known. A literature review
      was performed using specific search phrases, relating to hand-assisted or hybrid
      approaches to laparoscopic liver resection. Surgical results from 18 case series
      (HALS, nine series; hybrid technique, nine series), each with >= 10 patients,
      were analyzed. Results indicated that HALS was associated with a mean operative
      time of 82-264.5 min, an estimated blood loss of 82-300 mL, and a complication
      rate of 3.8-27.1%. Analysis of series involving the hybrid technique indicated a
      mean operative time of 111-366.5 min, an estimated blood loss of 93-936 mL, and a
      complication rate of 3.4-23.5%. In conclusion, there is insufficient evidence to
      conclude that any single approach is superior to the others, although HALS and
      the hybrid technique are useful when dealing with difficulties associated with
      pure laparoscopy. Conversely, the need for these two methods, which can function
      as a bridge to pure laparoscopic liver resection, may be overcome with
      appropriate training.

PMID- 25612234
TI  - Canagliflozin use in patients with renal impairment-Utility of quantitative
      clinical pharmacology analyses in dose optimization.
AB  - Canagliflozin (INVOKANATM) is approved as an adjunct to diet and exercise to
      improve glycemic control in adults with type 2 diabetes mellitus (T2DM).
      Canagliflozin inhibits renal sodium-glucose co-transporter 2 (SGLT2), thereby,
      reducing reabsorption of filtered glucose and increasing urinary glucose
      excretion. Given the mechanism of action of SGLT2 inhibitors, we assessed the
      interplay between renal function, efficacy (HbA1c reduction), and safety (renal
      adverse reactions). The focus of this article is to highlight the FDA's
      quantitative clinical pharmacology analyses that were conducted to support the
      regulatory decision on dosing in patients with renal impairment (RI). The metrics
      for assessment of efficacy for T2DM drugs is standard; however, there is no
      standard method for evaluation of renal effects for diabetes drugs. Therefore,
      several analyses were conducted to assess the impact of canagliflozin on renal
      function (as measured by eGFR) based on available data. These analyses provided
      support for approval of canagliflozin in T2DM patients with baseline eGFR >= 45
      mL/min/1.73 m(2) , highlighting a data-driven approach to dose optimization. The
      availability of a relatively rich safety dataset (ie, frequent and early
      measurements of laboratory markers) in the canagliflozin clinical development
      program enabled adequate assessment of benefit-risk balance in various patient
      subgroups based on renal function. 

PMID- 25612235
TI  - Bent pi-conjugated systems composed of three-dimensional benzoannulenes.
AB  - This article describes bent pi-conjugated systems composed of alternating o
      phenylene and Z-vinylene units. all-Z-[n]Benzo[4n]annulenes are higher homologues
      of dibenzocyclooctatetraene (DBCOT) with a concave pi system, and attempts were
      made to convert [20]- and [24]annulenes having partial belt structures of
      fullerenes and carbon nanotubes into [10]- and [12]phenacenes. A bent pi
      conjugated system composed of two DBCOT units showed dynamic syn-anti equilibrium
      in solution and behaved as dynamic molecular tweezers (DMTs). The syn isomers of
      the DMTs formed blue charge-transfer complexes with DDQ in solution, and this
      complexation and color change were applied to thermochromism. Furthermore, DMTs
      having two CN groups on each COT ring exhibited crystalline-state emission in the
      presence of solvent molecules, although almost no emission was observed in
      solution or the solid state. Based on this crystalline-state emission, a
      vapochromic system was established. The multifunctional properties of DMTs caused
      by the flexibility of the nonplanar pi system are summarized. 

PMID- 25612236
TI  - A year in review in Minerva Anestesiologica 2014.

PMID- 25612237
TI  - Peritoneal Dialysis is Limited by Kidney and Liver Volume in Autosomal Dominant
      Polycystic Kidney Disease.
AB  - We evaluated the influence of kidney volume (KV) and liver volume (LV) on
      continuation of peritoneal dialysis (PD) in patients with autosomal dominant
      polycystic kidney disease (PKD). Twenty-two PKD patients on PD were
      retrospectively investigated after being divided into two groups. Group 1
      comprised 15 patients who started PD at our hospital and group 2 was composed of
      seven patients referred from other hospitals for treatment of renomegaly by
      transcatheter arterial embolization (TAE) at 47.1 +/- 21.8 months after
      commencing PD. In group 1, KV for both kidneys (mean +/- SD) was 2787 +/- 1945 mL
      (range: 1043 to 6816 mL), LV was 2198 +/- 1139 mL (1005 to 4116 mL), and the
      total organ volume (TV=KV+LV) was 4985 +/- 1815 mL (2320 to 8912 mL). In the
      patient with the largest TV from group 1 (KV of 6816 mL, TV of 8912 mL, and
      TV/BMI ratio of 426, PD was stopped due to dialysate leakage. However, dialysate
      leakage did not occur in the other 14 patients (TV ? 7963 mL and TV/BMI ratio of
      353 at the start of PD). In group 2, KV was 5822 +/- 1597 mL (3832 to 8862 mL),
      LV was 1776 +/- 519 mL (1271 to 2671 mL), and TV was 7597 +/- 1431 mL (5505 to
      10358) before TAE. Leakage of dialysate did not occur with a mean infusion volume
      of 1530 +/- 370 mL (1000 mL to 2000 mL), even after renomegaly and hepatomegaly
      progressed to the maximum TV/BMI ratio of 359. Six patients from the two groups
      developed new abdominal hernias at 36 +/- 5 months (6-55 months) after starting
      PD. These findings suggest that performance of PD may be limited by renomegaly
      and hepatomegaly in patients with PKD.

PMID- 25612238
TI  - Melatonin uptake through glucose transporters: a new target for melatonin
      inhibition of cancer.
AB  - Melatonin is present in a multitude of taxa and it has a broad range of
      biological functions, from synchronizing circadian rhythms to detoxifying free
      radicals. Some functions of melatonin are mediated by its membrane receptors but
      others are receptor-independent. For the latter, melatonin must enter into the
      cell. Melatonin is a derivative of the amino acid tryptophan and reportedly
      easily crosses biological membranes due to its amphipathic nature. However, the
      mechanism by which melatonin enters into cells remains unknown. Changes in redox
      state, endocytosis pathways, multidrug resistance, glycoproteins or a variety of
      strategies have no effect on melatonin uptake. Herein, it is demonstrated that
      members of the SLC2/GLUT family glucose transporters have a central role in
      melatonin uptake. When studied by docking simulation, it is found that melatonin
      interacts at the same location in GLUT1 where glucose does. Furthermore, glucose
      concentration and the presence of competitive ligands of GLUT1 affect the
      concentration of melatonin into cells. As a regulatory mechanism, melatonin
      reduces the uptake of glucose and modifies the expression of GLUT1 transporter in
      prostate cancer cells. More importantly, glucose supplementation promotes
      prostate cancer progression in TRAMP mice, while melatonin attenuated glucose
      induced tumor progression and prolonged the lifespan of tumor-bearing mice. This
      is the first time that a facilitated transport of melatonin is suggested. In
      fact, the important role of glucose transporters and glucose metabolism in cell
      fate might explain some of the diverse functions described for melatonin. 

PMID- 25612239
TI  - Utility of neoadjuvant chemotherapy in the treatment of operable breast cancer.
AB  - Neoadjuvant chemotherapy (NAC) is a legitimate alternative to first-line surgical
      therapy for the treatment of breast cancer patients, as level one evidence shows
      the effect on overall survival is equivalent to that of adjuvant chemotherapy. In
      the treatment of women with operable breast cancer, NAC provides a number of
      potential advantages including: improving the chance of achieving breast
      conserving surgery, improving cosmesis after breast-conserving surgery,
      downstaging the breast and axilla, allowing time to fully consider surgical
      options, time for genetic testing and facilitating breast reconstruction in
      otherwise high-risk patients. However, in Australia, NAC is poorly utilized with
      less than 3% of women with operable breast cancer receiving NAC. This review
      discusses the potential harms and benefits of NAC, discusses areas of controversy
      in the use of NAC and describes how we have used NAC in our own practice. We
      conclude that if it is obviously necessary for the newly presenting breast cancer
      patient to have chemotherapy as part of the treatment, it is worth considering
      NAC. In many patients, the potential benefits of NAC outweigh the harms. However,
      maximizing these benefits is closely aligned with appropriate patient selection
      and timely multidisciplinary team communication. 

PMID- 25612240
TI  - De novo mutations in the BMPR2 gene in patients with heritable pulmonary arterial
      hypertension.
AB  - A substantial proportion of patients with pulmonary arterial hypertension (PAH)
      have mutations in the Bone Morphogenetic Protein Receptor type-2 (BMPR2) gene.
      PAH due to BMPR2 mutations is inherited as an autosomal dominant trait with
      several unique features, including a wide variety of mutations, reduced
      penetrance, a skewed gender ratio, variable expressivity and genetic
      anticipation. To address the genetic background of these unique features of BMPR2
      mutation, we conducted a systematic analysis of 15 PAH families with BMPR2
      mutation. The exonic protein coding sequence of BMPR2 was amplified by polymerase
      chain reaction and the products were sequenced directly to detect point mutations
      in BMPR2. Parental identification was carried out to confirm the parental
      relationship using multiplex 15 loci analysis. Combining mutation detection in
      family members with parental identification, we described three cases of de novo
      mutation in the BMPR2 gene by different modes in a PAH family. These de novo
      mutations may account for the wide variety of mutations in BMPR2. Taken together
      with the juvenile onset of the disease, there is possibly some balance of de novo
      mutations and untransmittable mutations which keeps the frequency of PAH low in
      the general population. 

PMID- 25612241
TI  - Rh(I)-catalyzed benzo/[7+1] cycloaddition of cyclopropyl-benzocyclobutenes and CO
      by merging thermal and metal-catalyzed C-C bond cleavages.
AB  - A Rh-catalyzed benzo/[7+1] cycloaddition of cyclopropyl-benzocyclobutenes (CP
      BCBs) and CO to benzocyclooctenones has been developed. In this reaction, CP-BCB
      acts as a benzo/7-C synthon and the reaction involves two C-C bond cleavages: a
      thermal electrocyclic ring-opening of the four-membered ring in CP-BCB and a Rh
      catalyzed C-C cleavage of the cyclopropane ring.

PMID- 25612242
TI  - Plasmids for C-terminal tagging in Saccharomyces cerevisiae that contain improved
      GFP proteins, Envy and Ivy.
AB  - Green fluorescent protein (GFP) has become an invaluable tool in biological
      research. Many GFP variants have been created that differ in brightness,
      photostability, and folding robustness. We have created two hybrid GFP variants,
      Envy and Ivy, which we placed in a vector for the C-terminal tagging of yeast
      proteins by PCR-mediated recombination. The Envy GFP variant combines mutations
      found in the robustly folding SuperfolderGFP and GFPgamma, while the Ivy GFP
      variant is a hybrid of GFPgamma and the yellow-green GFP variant, Clover. We
      compared Envy and Ivy to EGFP, SuperfolderGFP and GFPgamma and found that Envy is
      brighter than the other GFP variants at both 30 degrees C and 37 degrees C, while
      Ivy is the most photostable. Envy and Ivy are recognized by a commonly used anti
      GFP antibody, and both variants can be immunoprecipitated using the GFP TRAP
      Camelidae antibody nanotrap technology. Because Envy is brighter than the other
      GFP variants and is as photostable as GFPgamma, we suggest that Envy should be
      the preferred GFP variant, while Ivy may be used in cases where photostability is
      of the utmost importance.

PMID- 25612244
TI  - Determination of mutagenicity of the precipitate formed by sodium hypochlorite
      and chlorhexidine using the Ames test.
AB  - The aim of this study was to determine the direct mutagenic potential of any
      precipitate formed by combining sodium hypochlorite (NaOCl) and chlorhexidine
      (CHX). The precipitates formed by NaOCl and CHX were dissolved in 100% dimethyl
      sulfoxide and cultured with mutant Salmonella Typhimurium strains. The cells were
      observed for reverse mutation. The numbers of positive/mutated wells were
      statistically compared with those in the background plates using the two-sample
      proportion independent t-test. The precipitates were not found to be
      significantly more mutagenic than the background plates. Within the limitations
      of this study, the results suggest that the precipitates formed when sodium
      hypochlorite and chlorhexidine contact did not show mutagenic (and are therefore
      carcinogenic) potential.

PMID- 25612243
TI  - Clinical phenotypes as predictors of the outcome of skipping around DMD exon 45.
AB  - OBJECTIVE: Exon-skipping therapies aim to convert Duchenne muscular dystrophy
      (DMD) into less severe Becker muscular dystrophy (BMD) by altering pre-mRNA
      splicing to restore an open reading frame, allowing translation of an internally
      deleted and partially functional dystrophin protein. The most common single exon
      deletion-exon 45 (Delta45)-may theoretically be treated by skipping of either
      flanking exon (44 or 46). We sought to predict the impact of these by assessing
      the clinical severity in dystrophinopathy patients. METHODS: Phenotypic data
      including clinical diagnosis, age at wheelchair use, age at loss of ambulation,
      and presence of cardiomyopathy were analyzed from 41 dystrophinopathy patients
      containing equivalent in-frame deletions. RESULTS: As expected, deletions of
      either exons 45 to 47 (Delta45-47) or exons 45 to 48 (Delta45-48) result in BMD
      in 97% (36 of 37) of subjects. Unexpectedly, deletion of exons 45 to 46 (Delta45
      46) is associated with the more severe DMD phenotype in 4 of 4 subjects despite
      an in-frame transcript. Notably, no patients with a deletion of exons 44 to 45
      (Delta44-45) were found within the United Dystrophinopathy Project database, and
      this mutation has only been reported twice before, which suggests an
      ascertainment bias attributable to a very mild phenotype. INTERPRETATION: The
      observation that Delta45-46 patients have typical DMD suggests that the
      conformation of the resultant protein may result in protein instability or
      altered binding of critical partners. We conclude that in DMD patients with
      Delta45, skipping of exon 44 and multiexon skipping of exons 46 and 47 (or exons
      46-48) are better potential therapies than skipping of exon 46 alone.

PMID- 25612245
TI  - Multimodal Imaging and Choroidal Volumetric Changes After Half-fluence PDT in
      Central Serous Chorioretinopathy.
AB  - PURPOSE: The purpose of this study was to identify SD-OCT changes that correspond
      to leakage on fluorescein (FA) and indocyanine angiography (ICGA) and evaluate
      effect of half-fluence photodynamic therapy (PDT) on choroidal volume in chronic
      central serous choroidoretinopathy (CSC). METHODS: Retrospective analysis of
      patients with chronic CSC who had undergone PDT. Baseline FA and ICGA images were
      overlaid on SD-OCT to identify OCT correlates of FA or ICGA hyperfluorescence.
      Choroidal volume was evaluated in a subgroup of eyes before and after PDT.
      RESULTS: Twenty eyes were evaluated at baseline, of which seven eyes had
      choroidal volume evaluations at baseline and 3 months following PDT. SD-OCT
      changes corresponding to FA hyperfluorescence were subretinal fluid (73%), RPE
      microrip (50%), RPE double-layer sign (31%), RPE detachment (15%), and RPE
      thickening (8%). ICGA hyperfluoresence was correlated in 93% with hyperreflective
      spots in the superficial choroid. Choroidal volume decreased from 9.35 +/- 1.99
      to 8.52 +/- 1.92 and 8.04 +/- 1.7 mm(3) (at 1 and 3 months post PDT,
      respectively, p <= 0.001). CONCLUSIONS: We identified specific OCT findings that
      correlate with FA and ICGA leakage sites. SD-OCT is a valuable tool to localize
      CSC lesions and may be useful to guide PDT treatment. Generalized choroidal
      volume decrease occurs following PDT and extends beyond PDT treatment site.

PMID- 25612246
TI  - Fetoscopic laser ablation of vasa previa in pregnancy complicated by giant fetal
      cervical lymphatic malformation.

PMID- 25612247
TI  - The effects of WW2/WW3 domains of Smurf2 molecule on TGF-beta signaling and
      arginase I gene expression.
AB  - Smad ubiquitination regulatory factor 2 (Smurf2) consists of multiple WW domains
      which can interact with Smad7 molecule and inhibit signaling of transforming
      growth factor-beta (TGF-beta) cytokine. Arginase I (ArgI) is one of the main
      products of TGF-beta signaling that plays important roles in tumor escape and
      airway tissue fibrosis and remodeling in asthma. In this study, the effects of
      TAT fused to WW2/WW3 (TAT-WW2/WW3) recombinant protein on TGF-beta signaling and
      ArgI gene expression were evaluated on J774A.1 cell culture. For this purpose,
      interaction of TAT-WW2/WW3 with Smad7, mRNA expression of ArgI, and
      phosphorylated Smad3 (P-Smad3) were analyzed in TAT-WW2/WW3-treated J774A.1 cell.
      The results showed interaction of TAT-WW2/WW3 with Smad7, downregulation of ArgI
      gene expression (P < 0.05), and higher amount of P-Smad3 in the TAT-WW2/WW3
      treated cells. In conclusion, we suggest that TAT-WW2/WW3 could interfere with
      TGF-beta signaling and reduce ArgI gene expression. Since, ArgI has important
      effects on tissue remodeling in asthma and cancer progression, so these findings
      could be used to develop a new approach in the treatment of asthma and cancers. 

PMID- 25612248
TI  - Prostaglandin E1 Treatment for Lumbar Spinal Canal Stenosis: Review of the
      Literature.
AB  - BACKGROUND: The important pathophysiologic factor of neurogenic intermittent
      claudication (NIC) in lumbar spinal canal stenosis (LSCS) has been reported to be
      the reduction in intraneural blood flow and a state of relative ischemia in nerve
      tissues. Prostaglandin E1 (PGE1) presumably improves symptoms in patients with
      LSCS by improving the blood flow in the cauda equina and nerve roots through its
      vasodilation and antiplatelet aggregation effects. The purpose of the study was
      to summarize the results of previous studies regarding PGE1 treatment for LSCS
      and to describe the details of PGE1 treatment to all physicians who take care of
      patients with LSCS. METHODS: Review of the literature. RESULTS: There are 3 PGE1
      related products that have been used clinically for the treatment of LSCS: PGE1,
      lipo-PGE1, and limaprost (PGE1 derivative). Experimental studies have been
      performed to verify the efficacy of PGE1 treatment for LSCS. Many studies have
      reported clinical outcomes of PGE1 treatment in patients with LSCS. Overall,
      previous studies examining PGE1 treatment for LSCS demonstrate improvement in
      several clinical outcome measures such as the visual analog scale, Japanese
      Orthopaedic Association score, and NIC distance, although most of the studies
      have only short-term follow-up. CONCLUSIONS: Based on the results of previous
      studies, PGE1 treatment may be an option as a conservative treatment for LSCS.
      However, future studies with high-quality and long-term follow-up are necessary.
      Future studies also should include refinement of indications, administration
      period, as well as comparisons between PGE1 treatment and other conservative
      treatments such as epidural injection.

PMID- 25612249
TI  - Genomic and gene expression responses to genotoxic stress in PAC2 zebrafish
      embryonic cell line.
AB  - PAC2 cell line is, along most of the developed zebrafish cell lines, poorly
      characterized concerning its response to genotoxicants. To define the PAC2 cell
      line response to different forms of genotoxic stress, we exposed the cells to
      model genotoxic agents (benzo[a]pyrene, B[a]P, and ethyl methanesulfonate) and
      subsequently monitored DNA damage and alterations by using the battery of tests,
      including the Comet assay, quantitative random-amplified polymorphic DNA and
      amplified fragment length polymorphism. The expression of several DNA repair
      (xpc, xpd, hr23b, rad51, msh2) and oxidative stress response (sod (Cu/Zn)) genes
      was monitored as well. To obtain an indication of the PAC2 cell line metabolizing
      capacity, the expression of genes belonging to cyp1, cyp2 and cyp3 families was
      assessed upon exposure to B[a]P. Genotoxic responses were observed in all the
      used methods, and quantitative random-amplified polymorphic DNA and amplified
      fragment length polymorphism proved to be more sensitive by revealing DNA
      alterations even when the Comet assay indicated lack of significant damage. The
      PAC2 cell line demonstrated basal and B[a]P-induced expression of several cyp
      genes, suggesting its ability to metabolize indirect acting xenobiotics to a
      certain point. Based on these results, PAC2 cells seem to be sensitive zebrafish
      in vitro model in the genotoxicity assessment of the direct acting genotoxicant;
      however, they are less sensitive toward the indirect acting genotoxicant due to
      their limited metabolizing properties.

PMID- 25612250
TI  - Estimating the lifetime cost of childhood obesity in Germany: Results of a Markov
      Model.
AB  - BACKGROUND: Child obesity is a growing public health concern. Excess weight in
      childhood is known to be associated with a high risk of obesity and obesity
      related comorbidities in adulthood. OBJECTIVES: This study quantifies lifetime
      excess costs of overweight and obese adults in Germany taking the history of
      obesity in childhood into account. METHODS: A two-stage Markov cohort state
      transition model was developed. At stage 1, the distribution of body mass index
      (BMI) categories was tracked from childhood (ages 3-17) to adulthood (age 17 and
      up). Based on these results, it was distinguished whether adults had been normal
      in weight or overweight/obese as child. At stage 2, age-specific and lifetime
      costs from age 18 onwards were simulated in two further Markov cohort models, one
      for each of the two BMI groups. Model parameter values were obtained from the
      German Interview and Examination Survey for Children and Adolescents (KiGGS), the
      German Microcensus 2009 and published literature. RESULTS: When compared with
      normal weight adults, lifetime excess costs are higher among adults who had been
      overweight or obese at any point during childhood. For 18-year-old women (men),
      who have been overweight/obese during their childhood (ages 3-17), undiscounted
      lifetime excess costs are estimated at ?19,479 (?14,524), with 60% (67%)
      occurring beyond age 60. Discounted (3%) lifetime excess costs are considerably
      lower, amounting to ?4262 for men and ?7028 for women. CONCLUSIONS: Because
      childhood obesity determines healthcare costs occurring in adulthood,
      interventions preventing the persistence of child obesity and obesity-related
      comorbidities during adulthood could have a substantial impact on reducing the
      burden of the obesity epidemic.

PMID- 25612252
TI  - Carbo-quinoids: stability and reversible redox-proaromatic character towards
      carbo-benzenes.
AB  - The carbo-mer of the para-quinodimethane core is stable within in a bis(9
      fluorenylidene) derivative. Oxidation of this carbo-quinoid with MnO2 in the
      presence of SnCl2 and ethanol affords the corresponding p-bis(9-ethoxy-fluoren-9
      yl)-carbo-benzene. The latter can be in turn converted back into the carbo
      quinoid by reduction with SnCl2 , thus evidencing a chemical reversibility of the
      interconversion between a pro-aromatic carbo-quinoid and an aromatic carbo
      benzene, and is reminiscent of the behavior of the benzoquinone/hydroquinone
      redox couple (in the red-ox opposite sense). 

PMID- 25612251
TI  - Adipose tissue as an immunological organ.
AB  - OBJECTIVE: This review will focus on the immunological aspects of adipose tissue
      and its potential role in development of chronic inflammation that instigates
      obesity-associated comorbidities. METHODS: The review used PubMed searches of
      current literature to examine adipose tissue leukocytosis. RESULTS AND
      CONCLUSIONS: The adipose tissue of obese subjects becomes inflamed and
      contributes to the development of insulin resistance, type 2 diabetes, and
      metabolic syndrome. Numerous immune cells including B cells, T cells,
      macrophages, and neutrophils have been identified in adipose tissue, and obesity
      influences both the quantity and the nature of immune cell subtypes, which
      emerges as an active immunological organ capable of modifying whole-body
      metabolism through paracrine and endocrine mechanisms. Adipose tissue is a large
      immunologically active organ during obesity and displays hallmarks of both and
      innate and adaptive immune response. Despite the presence of hematopoietic
      lineage cells in adipose tissue, it is unclear whether the adipose compartment
      has a direct role in immune surveillance or host defense. Understanding the
      interactions between leukocytes and adipocytes may reveal the clinically relevant
      pathways that control adipose tissue inflammation and is likely to reveal
      mechanisms by which obesity contributes to increased susceptibility to both
      metabolic and certain infectious diseases.

PMID- 25612254
TI  - Aging interventions get human.

PMID- 25612253
TI  - Change point testing in logistic regression models with interaction term.
AB  - A threshold effect takes place in situations where the relationship between an
      outcome variable and a predictor variable changes as the predictor value crosses
      a certain threshold/change point. Threshold effects are often plausible in a
      complex biological system, especially in defining immune responses that are
      protective against infections such as HIV-1, which motivates the current work. We
      study two hypothesis testing problems in change point models. We first compare
      three different approaches to obtaining a p-value for the maximum of scores test
      in a logistic regression model with change point variable as a main effect. Next,
      we study the testing problem in a logistic regression model with the change point
      variable both as a main effect and as part of an interaction term. We propose a
      test based on the maximum of likelihood ratios test statistic and obtain its
      reference distribution through a Monte Carlo method. We also propose a maximum of
      weighted scores test that can be more powerful than the maximum of likelihood
      ratios test when we know the direction of the interaction effect. In simulation
      studies, we show that the proposed tests have a correct type I error and higher
      power than several existing methods. We illustrate the application of change
      point model-based testing methods in a recent study of immune responses that are
      associated with the risk of mother to child transmission of HIV-1.

PMID- 25612255
TI  - Influence of the basal core promoter and precore mutation on replication of
      hepatitis B virus and antiviral susceptibility of different genotypes.
AB  - Mutations in the basal core promoter (BCP) and precore (PC) regions of the
      hepatitis B virus (HBV) are more common in genotypes B and C than in genotype A,
      suggesting that these mutations might affect replication competency depending on
      genotype. The purpose of the study was to investigate the influence of these
      mutations on the capacity of HBV for replication and antiviral drug
      susceptibility according to genotype. Genotypes A, B, and C of HBV strains with a
      BCP mutation, PC mutation, or BCP + PC mutation were made by site-directed
      mutagenesis. Replication competency of each construct and susceptibility to
      nucleos(t) ide analogues were tested in an Huh7 cell line. In genotype A, the BCP
      and BCP + PC mutations increased the viral replication around 6.5 times compared
      with the wild type, and the PC mutation alone similarly increased the viral
      replication around three times. In genotypes B and C, all three mutant types
      increased viral replication to a similar extent, regardless of mutation pattern.
      Interestingly, the BCP mutation appeared to have a greater effect on viral
      replication in genotype A than in genotypes B and C. This finding was unexpected
      because the BCP mutation is more common in HBV genotypes B and C. Moreover, the
      BCP, PC, and BCP + PC mutations decreased the sensitivity of HBV to antiviral
      agents to various degrees (2- to 10-fold) regardless of genotype. In conclusion,
      BCP and PC mutations increased viral replication regardless of HBV genotype and
      decreased in vitro antiviral susceptibility to the nucleos(t) ide analogues.

PMID- 25612257
TI  - Failed calibration of anesthesia machine due to look-alike oxygen sensors.
AB  - Labels and medications with similar appearances have the potential to harm
      patients and cause delays in hospital services. We report a problem involving the
      Maxtec MAX-1 and MAX-11 oxygen sensors which are commonly used on anesthesia
      machines. These oxygen sensors have nearly identical labels which resulted in
      inadvertent interchanging of the sensors. The incident required the replacement
      of a MAX-11 sensor with a MAX-1 sensor to ensure proper functioning of the
      anesthesia machine. Identification of these cases can educate health care
      professionals of potential sources of labeling errors and safety issues and can
      also bring about Food and Drug Administration policy changes. 

PMID- 25612258
TI  - Severe anaphylactic shock due to ethylene oxide in a patient with
      myelomeningocele: successful exposure prevention and pretreatment with
      omalizumab.
AB  - Ethylene oxide (EO) is a highly reactive gas widely used for sterilization of
      medical devices, for example, plastic materials and ventriculoperitoneal shunts.
      Allergic reactions to EO are rare and have been observed mainly in patients
      during hemodialysis and myelomeningocele patients. We describe severe anaphylaxis
      to EO in a patient with myelomeningocele during general anesthesia. A detailed
      description is provided about the prevention measures aimed at reducing exposure
      to EO including a novel approach by resterilization with plasma. Also,
      pretreatment with omalizumab was implemented for the first time in such a case.
      With these measures, further surgeries in our patient were uneventful. 

PMID- 25612259
TI  - Emergent retrograde tracheal intubation in a 3-year-old with stevens-johnsons
      syndrome.
AB  - A 3-year-old girl suffering from Stevens-Johnsons Syndrome with severe sloughing
      of the oropharyngeal mucosa was brought to the operating room for an emergent
      tracheostomy after multiple failed attempts to intubate the trachea in the
      pediatric intensive care unit. However, a retrograde tracheal intubation was
      successfully performed in the operating room to secure her airway, after which a
      tracheostomy was performed. Retrograde intubation can be a quick and effective
      method for securing the difficult airway. 

PMID- 25612260
TI  - Simultaneous antiphospholipid syndrome and heparin-induced thrombocytopenia in a
      single patient.
AB  - Antiphospholipid syndrome and heparin-induced thrombocytopenia are immune
      mediated thrombotic conditions initiated by 2 distinct antibodies each targeting
      a discrete protein-antigen complex. Although produced by 2 different types of
      antibodies, they are similar in their autoimmune and pathophysiologic mechanisms.
      We present a case with simultaneous antiphospholipid syndrome and heparin-induced
      thrombocytopenia syndromes that sheds light on the correlation between these 2
      syndromes. 

PMID- 25612261
TI  - Diet and irritable bowel syndrome.
AB  - PURPOSE: of review Those who suffer from irritable bowel syndrome (IBS) have long
      reported the frequent precipitation of their symptoms in relation to food
      ingestion and have often been convinced that certain foods were especially
      problematic. However, until very recently, research on the responses to food or
      individual dietary constituents, in IBS, has been scarce. This review addresses
      recent literature on diet and IBS. RECENT FINDINGS: The complexity of food
      symptom interactions in IBS is being revealed in recent and ongoing research.
      Such studies have revealed the variable effects of fibre in IBS and the
      susceptibility of IBS individuals to the ingestion of poorly digested and
      absorbed carbohydrates. The latter has led to the widespread adoption of the low
      fermentable oligosaccharides, disaccharides, monosaccharides and polyols
      (FODMAPs) diet. Less certain is the role of another widely adopted dietary
      strategy, gluten restriction. Diet-microbe interactions are critical to the
      homeostasis of the gut microbiome in health and may well be disturbed in disease;
      enthusiasm continues, therefore, for the use of probiotics in IBS. SUMMARY: Food
      is a common precipitant of symptoms in IBS and recent research has focused on the
      role(s) of individual dietary constituents in IBS and on fibre, FODMAPs, gluten
      and probiotics, in particular. Each may have a role in certain IBS sufferers.

PMID- 25612264
TI  - Isosulfan Blue Dye Anaphylaxis Presenting as Impaired Ability to Ventilate via a
      Laryngeal Mask Airway.
AB  - A 44-year-old woman presented for sentinel node biopsy and segmental mastectomy.
      After anesthetic induction, a laryngeal mask airway was placed, and ventilation
      was satisfactory. Three minutes after isosulfan blue dye injection, ventilation
      became difficult. The laryngeal mask airway was removed, and an endotracheal tube
      was easily placed. Twenty minutes later, she became hypotensive and unresponsive
      to phenylephrine, ephedrine, and vasopressin. With erythema and swelling in her
      arm and chest, low-dose epinephrine was titrated until her mean arterial blood
      pressure stabilized. Serum tryptase was increased to 27.2 MUg/L (normal 0.4-10.9
      MUg/L). 

PMID- 25612263
TI  - The development and initial evaluation of a realistic simulated SPECT dataset
      with simultaneous respiratory and cardiac motion for gated myocardial perfusion
      SPECT.
AB  - We developed a realistic simulation dataset for simultaneous respiratory and
      cardiac (R&C) gated SPECT/CT using the 4D NURBS-based Cardiac-Torso (NCAT)
      Phantom and Monte Carlo simulation methods, and evaluated it for a sample
      application study. The 4D NCAT phantom included realistic respiratory motion and
      beating heart motion based on respiratory gated CT and cardiac tagged MRI data of
      normal human subjects. To model the respiratory motion, a set of 24 separate 3D
      NCAT phantoms excluding the heart was generated over a respiratory cycle. The
      beating heart motion was modeled separately with 48 frames per cardiac cycle for
      each of the 24 respiratory phases. The resultant set of 24  *  48 3D NCAT
      phantoms provides a realistic model of a normal human subject at different phases
      of combined R&C motions. An almost noise-free SPECT projection dataset for each
      of the 1152 3D NCAT phantoms was generated using Monte Carlo simulation
      techniques and the radioactivity uptake distribution of (99m)Tc sestamibi in
      different organs. By grouping and summing the separate projection datasets,
      separate or simultaneous R&C gated acquired data with different gating schemes
      could be simulated. In the initial evaluation, we combined the projection
      datasets into ungated, 6 respiratory-gates only, 8 cardiac-gates only, and
      combined 6 respiratory-gates & 8 cardiac-gates projection datasets. Each dataset
      was reconstructed using 3D OS-EM without and with attenuation correction using
      the averaged and respiratory-gated attenuation maps, and the resulting
      reconstructed images were compared. These results were used to demonstrate the
      effects of R&C motions and the reduction of image artifact due to R&C motions by
      gating and attenuation corrections. We concluded that the realistic 4D NCAT
      phantom and Monte Carlo simulated SPECT projection datasets with R&C motions are
      powerful tools in the study of the effects of R&C motions, as well as in the
      development of R&C gating schemes and motion correction methods for improved
      SPECT/CT imaging. 

PMID- 25612265
TI  - Third-degree heart block during spinal anesthesia for cesarean delivery.
AB  - A 34-year-old parturient developed third-degree atrioventricular block, in the
      setting of hypotension, after spinal anesthesia for cesarean delivery. The
      arrhythmia fully resolved with anticholinergic and sympathomimetic drugs.
      Considering the increasing maternal morbidity and potential risk of maternal
      cardiac arrest, this critical state is reviewed, and a treatment algorithm is
      suggested. 

PMID- 25612266
TI  - General anesthesia treatment of propriospinal myoclonus in a patient with
      fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva, a rare and severely disabling genetic
      condition, is characterized clinically by progressive ossification of skeletal
      muscle and connective tissue and congenital malformations of the great toes.
      Recurrent episodes of heterotopic ossification (flare-ups) lead to increasing
      loss of mobility as joints become progressively affected. We report the case of a
      young woman with fibrodysplasia ossificans progressiva who had recurrent,
      debilitating myoclonus that was refractory to conventional therapies but was
      relieved for prolonged periods after general anesthesia was administered. 

PMID- 25612267
TI  - Pneumocephalus after lumbar epidural steroid injection: a case report and review
      of the literature.
AB  - Pneumocephalus may occur after inadvertent injection of air into the subarachnoid
      space while performing epidural anesthesia using a loss-of-resistance technique
      with air in the syringe. We report a case of pneumocephalus after an interlaminar
      epidural steroid injection using the loss-of-resistance to air technique. In this
      report, we examine the etiology, the expected course of symptoms, and resolution,
      as well as treatment, of pneumocephalus following a systematic literature review.

PMID- 25612268
TI  - Synthesis of novel azole-fused quinazolines via one-pot, sequential Ullmann-type
      coupling and intramolecular dehydrogenative C-N bonding.
AB  - An efficient one-pot sequential procedure is described for the synthesis of novel
      azole-fused quinazolines through Pd/Cu co-catalyzed, Ullmann-type coupling
      followed by cross dehydrogenative coupling of various azoles such as 1H
      imidazole, 1H-benzimidazole and 1H-1,2,4-triazole with 2-(2-bromophenyl)-1H
      imidazole/benzimidazoles. The developed strategy has offered good yields (52-81%)
      of diverse N-fused tetra-, penta- and hexa-cyclic frameworks in a single step. 

PMID- 25612270
TI  - Editorial comment: previously undiagnosed Reinke edema as a cause of immediate
      postextubation inspiratory stridor.

PMID- 25612269
TI  - Previously undiagnosed Reinke edema as a cause of immediate postextubation
      inspiratory stridor.
AB  - Reinke edema (RE) is an uncommon lesion of the vocal folds and a potential cause
      of complications during airway management. We report the case of a woman with
      previously unknown RE admitted to the intensive care unit who experienced
      postextubation inspiratory stridor immediately after separation from mechanical
      ventilation. RE should be considered among causes of postextubation stridor. 

PMID- 25612271
TI  - Transcranial Doppler-guided deairing of a pediatric ventricular assist device:
      experience with twins.
AB  - We report the intraoperative courses of 2 consecutive Berlin Heart Excor(r)
      Pediatric Ventricular Assist Device implantations, in which transcranial Doppler
      ultrasonography helped to detect macroscopically undetected residual air bubbles
      captured in the pump after air removal had been correctly performed according to
      manufacturer's specifications. Our experience with these cases suggests that a
      beat-to beat deairing maneuver guided by transcranial Doppler is a useful
      strategy for reducing cerebral exposure to perioperative gaseous microembolism. 

PMID- 25612272
TI  - Spontaneous intracranial hypotension syndrome treated with fludrocortisone.
AB  - Spontaneous intracranial hypotension is a rare syndrome characterized by
      orthostatic headache not associated with trauma or dural puncture. In most cases,
      it is caused by a spontaneous spinal cerebrospinal fluid leakage as demonstrated
      by neuroradiological studies. The standard of care consists of conservative
      treatment including bed rest, hydration, and administration of caffeine or
      glucocorticoids. When such conservative therapy fails, an epidural blood patch is
      recommended. In this report, we describe the treatment of 2 patients with
      spontaneous intracranial hypotension who failed conservative treatment and went
      on to have complete and sustained resolution of their symptoms after the
      administration of oral fludrocortisone. 

PMID- 25612273
TI  - Successful pregnancy and delivery in a patient with Carney complex: implications
      for anesthesiologists.
AB  - Carney complex is an autosomal dominant condition with widespread manifestations,
      including cardiac myxomas, nerve sheath tumors, and endocrinopathies. Although
      often associated with infertility, there are several reports of successful
      pregnancies in patients with Carney complex. However, none of the previous
      reports describe anesthetic considerations. Herein, we present a patient with
      Carney complex who successfully delivered vaginally with labor epidural
      analgesia. 

PMID- 25612274
TI  - [ST-elevation myocardial infarction: angiotensin receptor blockers are effective
      with preserved ejection fraction].

PMID- 25612275
TI  - [Intensive Care: vitamin D replacement helps in critically ill patients].

PMID- 25612276
TI  - [Environmental respiratory diseases: chronic bronchitis: unaffected by air
      pollution?].

PMID- 25612277
TI  - [Perioperative beta-blockers: not suitable for all patients].

PMID- 25612278
TI  - [19-year-old boy with congenital ventricular septal defect and increased
      pressures in right heart catheterization].

PMID- 25612279
TI  - [Acute chest pain: "The big 3" in the emergency room].

PMID- 25612280
TI  - [Pulmonary embolism].
AB  - Acute pulmonary embolism is an important differential diagnosis of acute chest
      pain. The clinical signs are often non-specific. However, diagnosis and therapy
      must be done quickly in order to reduce morbidity and mortality. The new (2014)
      European guidelines for acute pulmonary embolism (PE) focus on risk-adapted
      diagnostic algorithms and prognosis adapted therapy concepts. According to the
      hemodynamic presentation the division in a high-risk group (unstable patient with
      persistent hypotension or shock) or in non-high-risk groups (hemodynamically
      stable) was proposed. In the high-risk group the immediate diagnosis is usually
      done by multidetector spiral computed tomography (MDCT) and primarily the medical
      therapy of right ventricular dysfunction and thrombolysis is recommended.In the
      non-high-risk group, this is subdivided into an intermediate-risk group and low
      risk group, the diagnosis algorithm based on the PE-pretest probability-
      determined by validated scores. Moreover, the diagnosis is usually secured by
      MDCT--the new gold standard in the PE-diagnosis, scores, or it can be primarily
      ruled out due to the high negative predictive value of D-dimer determination. To
      improve the prognostic risk stratification in non-high-risk group patients the
      additional detection of right ventricular dysfunction (MDCT, echocardiography),
      cardiac biomarkers (troponin, NT proBNP) and validated scores (e.g. Pulmonary
      Embolism Severity Index) is recommended. Therefore, the intermediate-risk group
      can be further subdivided. For treatment of non-high-risk group patients, the
      initial anticoagulation (except those with severe renal insufficiency) using low
      molecular weight heparin/fondaparinux and conversion to vitamin-K antagonists or
      alternatively with direct oral anticoagulants (DOAK) is recommended.
      Hemodynamically stable patients with right ventricular dysfunction and myocardial
      ischemia (Intermediate-high-risk group patients) but with clinically progressive
      hemodynamic decompensation may benefit from systemic thrombolysis as well. Due to
      the high risk of bleeding in the PEITHO study, however, a critical individual
      risk-benefit evaluation should be done. A dose reduced systemic or local
      ultrasound-assisted thrombolysis could gain importance in the future. For very
      selected patients in the low-risk group early outpatient treatment could be
      considered.The diagnosis and treatment of pulmonary embolism remains complex.
      Improved algorithms support the diagnosis procedures and therapy decisions.
      Direct oral anticoagulants are a new first-line therapy alternative for
      hemodynamically stable non-high-risk patients.

PMID- 25612281
TI  - [Acute coronary syndrome].
AB  - The acute coronary syndrome (ACS) still remains a common disease in the
      preclinical as well as in the intrahospital emergency setting. Different clinical
      types of an ACS, such as unstable angina (UA), non-ST-elevation myocardial
      infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) have to be
      differentiated diagnostically, prognostically and in terms of the best
      therapeutic strategy. Due to the broad and early use of percutaneous coronary
      intervention (PCI) as well as due to innovations in the antithrombotic and
      anticoagulation regime with the use of more effective P2Y12-receptor antagonists
      as well as the use of Fondaparinux and Bivalirudin, a continuous improvement of
      the prognosis and reduction of ischemic events could be achieved in ACS patients
      over the last few years. However, the increased bleeding rate, particularly when
      using those new substances, remains a relevant problem. Future studies are
      warranted to clarify if certain combinations of substances may be better suited
      to achieve the optimal balance between reduction of cardiovascular events on the
      one hand and bleeding risk on the other hand. 

PMID- 25612282
TI  - [Acute aortic syndrome].
AB  - Acute aortic syndrome (AAS) is a rather rare but often life-threatening cause of
      thoraco-abdominal pain. AAS includes acute aortic dissection (AD), intramural
      hematoma (IMH) and penetrating atherosclerotic ulcer (PAU), in which the latter
      may progress to AD. Suddenly emerging severe pain localized in the chest, back or
      the abdomen is rather characteristic for acute AD, but painless courses of the
      disease are also possible. Rapid diagnosis and treatment are crucial for
      prognosis and survival. Aortic contrast-enhanced computed tomography is the
      method of choice due to its broad availability, distinguished accuracy and rapid
      feasibility. In instable patients, transoesophagel echocardiography by an
      experienced examiner is also applicable. Patients suffering from Type A AD need
      urgent surgery in most cases, patients. 

PMID- 25612283
TI  - [Systemic Adamantiades-Behcet's disease: adverse effects of an otherwise
      successful therapy with interferon-alpha-2a].
AB  - BACKGROUND: Adamantiades-Behcet's disease is an immune-mediated vasculitis with
      relapsing course. It is characterised by the classic clinical trias of oral
      aphthous ulcers, genital ulcers and uveitis. HISTORY AND FINDINGS: A 37-year-old
      woman suffered from systemic Adamantiades-Behcet disease with recurrent uveitis,
      oral ulcers, genital ulcers, arthralgia, erythema nodosum and folliculitis.
      COURSE AND TREATMENT: Longterm interferon-alpha-2a (IFNalpha-2a) led to reduction
      of the clinical manifestations except for occasional occurrence of oral ulcers.
      One year after initiation of treatment however, the patient developed symptomatic
      hyperprolactinemia of unknown etiology. CONCLUSION: Even in otherwise successful
      treatment with IFNalpha-2a possible side effects and complications of treatment
      can affect the course. Mastodynia and hyperprolactinemia have not yet been
      described as potential side effects of IFNalpha-2a.

PMID- 25612284
TI  - [How to do: kidney biopsy].

PMID- 25612285
TI  - [Psychocardiology: how heart and mind interact].
AB  - Patients with heart disease often suffer from psychological comorbidities in
      addition to various physical impairments. These mental disorders reduce the
      quality of life and have a negative effect on the development and course of heart
      diseases. Particularly the occurrence of depression, anxiety and post-traumatic
      stress disorder (PTSD) may lead to an increase in hospitalization-, morbidity-,
      and mortality rates. Early diagnosis of psychological disorders in patients with
      cardiovascular disease and consecutive treatment is therefore desirable. In this
      context, psychocardiology addresses the interaction of cardiac disease and
      psychological alterations as well as the influencing psychosocial factors. 

PMID- 25612286
TI  - [Imported tropical fish causes ciguatera fish poisoning in Germany].
AB  - Ciguatera is a seafood-borne illness caused by consumption of tropical fish
      contaminated with ciguatoxins, lipophilic polyethers that are produced in benthic
      dinoflagellates and accumulate through the marine food chain. Ciguatera cases in
      Europe usually occur in travellers returning from tropical and subtropical
      regions of the Pacific and Carribean, where ciguatera is endemic. In 2012,
      several cases of ciguatera occurred in Germany due to sale of contaminated fish
      products originating from the Indian Ocean. Although the symptomatology in these
      cases were typical of ciguatera, with patients reporting gastrointestinal
      discomfort including nausea, vomiting and diarrhea as well as neurological
      effects including widespread intense pruritus, paresthesias, hypothermia or
      altered temperature sensation and diffuse pain, correct diagnosis was delayed in
      all cases due to lack of awareness of the treating medical practitioners. In
      light of increasing global mobility, trade, and occurrence of ciguatoxic fish in
      previously non-endemic areas, ciguatera should be considered as a possible
      diagnosis if gastrointestinal and neurological symptoms occur shortly after
      consumption of fish. 

PMID- 25612287
TI  - [Physician-assisted suicide: can unbearable suffering be a criterion?].

PMID- 25612288
TI  - [How do Turkish immigrants evaluate cultural sensitivity in a German tertiary
      hospital?].
AB  - BACKGROUND: Culturally adequate medical care is a goal in Germany, but
      quantitative data concerning inpatients is lacking. METHODS: Inpatients of a
      German tertiary hospital: Turkish migrants (T) and Germans (G) were interviewed
      in their respective native language. RESULTS: 121 T and 121 G were interviewed.
      97.5% of T were Muslims, 82.6% of G were Christians. 88.5% of T judged religion
      as "important" or "very important" (G: 35.8%). 50.8% of T saw their opportunity
      to pray in the hospital as "bad" or "very bad" (G: 0.9%). Keeping to Islamic
      dietary rules in the hospital was "difficult" or "very difficult" for 90% of T.
      For 79.0% of female T care by a same-sex staff was "important" or "very
      important" (female G: 36.3%, male T: 40.0%, male G: 7.7%). The presence of a same
      sex person during examinations or treatments was "much" or "very much"
      appreciated by 69.7% of female T, if same-sex care was impossible (female G:
      25.4%, male T: 28.9%, male G: 6.1%). A retrospective analysis revealed that 5.8%
      of all 8988 hospital admissions during the period of study recruitment were
      Turkish migrants. CONCLUSION: To meet the needs of Turkish migrants German
      hospitals should improve the opportunity for Muslims to pray. Additionally, the
      cooperation with local imams should be sought. Precise descriptions of food
      ingredients or an adapted menu could help T to deal with Muslim dietary
      commandments. A culturally sensitive hospital should take into account that
      female as well as male T prefer to be cared of by same-sex physicians and nurses.

PMID- 25612289
TI  - [Response to Terlipressin and albumin is associated with improved outcome in
      patients with cirrhosis and hepatorenal syndrome].
AB  - BACKGROUND AND AIM: Hepatorenal syndrome (HRS) is a severe but potentially
      reversible complication in patients with cirrhosis. Untreated it is associated
      with a poor prognosis. Several randomized controlled trials (RCT) demonstrated
      that treatment with terlipressin and albumin improves renal function. However the
      effect on overall survival is unclear. Aim of the study was to gain further
      insight into the effect of terlipressin treatment in patients with HRS on renal
      function, overall survival and survival without liver transplantation or renal
      replacement. METHODS: All patients presenting with HRS and treated with
      terlipressin in our tertiary referral liver and transplantation center between
      April 2013 and April 2014 were included. Clinically relevant parameters such as
      response to therapy, overall survival and transplant- and renal-replacement-free
      survival were prospectively investigated. RESULTS: Overall 57 patients were
      prospectively followed over a median of 65 days. In the majority of patients
      cirrhosis was in an advanced stage (Child-Pugh C: 46; 81%). Median cumulative
      terlipressin dosage and treatment duration were 20 mg and 5 days, respectively.
      Complete or partial response to terlipressin with recovery from HRS was observed
      in 20 and 3 out of 57 patients (51%; 5%). Median overall survival was
      significantly better in patients with response to terlipressin than in patients
      with non-response (167 vs. 27 days; p > 0.0001), as well as median survival free
      of liver transplantation and renal-replacement-therapy (81 vs. 4 days; p >
      0.0001). In uni- and multivariate analysis, non-response was associated with a
      high baseline serum-bilirubin-concentration. CONCLUSION: Terlipressin in
      combination with albumin is effective in the majority of patients with HRS.
      Response to therapy is associated with improved survival.

PMID- 25612290
TI  - Terbium-based time-gated Forster resonance energy transfer imaging for evaluating
      protein-protein interactions on cell membranes.
AB  - Fluorescence imaging of cells and subcellular compartments is an essential tool
      to investigate biological processes and to evaluate the development and
      progression of diseases. In particular, protein-protein interactions can be
      monitored by Forster resonance energy transfer (FRET) between two proximal
      fluorophores that are attached to specific recognition biomolecules such as
      antibodies. We investigated the membrane expression of E- and N-cadherins in
      three different cell lines used as model systems to study epithelial to
      mesenchymal transition (EMT) and a possible detection of circulating tumour cells
      (CTCs). EMT is a key process in cancer metastasis, during which epithelial
      markers (such as E-cadherin) are down-regulated in the primary tumour whereas
      mesenchymal markers (such as N-cadherin) are up-regulated, leading to enhanced
      cell motility, intravasation, and appearance of CTCs. Various FRET donor-acceptor
      pairs and protein recognition strategies were utilized, in which Lumi4-Tb terbium
      complexes (Tb) and different organic dyes were conjugated to several distinct E-
      and N-cadherin-specific antibodies. Pulsed excitation of Tb at low repetition
      rates (100 Hz) and time-gated (TG) imaging of both the Tb-donor and the dye
      acceptor photoluminescence (PL) allowed efficient detection of the EMT markers as
      well as FRET in the case of sufficient donor-acceptor proximity. Efficient FRET
      was observed only between two E-cadherin-specific antibodies and further
      experiments indicated that these antibodies recognized the same E-cadherin
      molecule, suggesting a limited accessibility of cadherins when they are clustered
      at adherens junctions. The investigated Tb-to-dye FRET systems provided reduced
      photobleaching compared to the AlexaFluor 488-568 donor-acceptor pair. Our
      results demonstrate the applicability and advantages of Tb-based TG FRET for
      efficient and stable imaging of antibody-antibody interactions on different cell
      lines. They also reveal the limitations of interpreting colocalization on cell
      membranes in the case of lacking FRET signals. 

PMID- 25612291
TI  - Borderline personality disorder and childhood maltreatment: a genome-wide
      methylation analysis.
AB  - Early life adversity plays a critical role in the emergence of borderline
      personality disorder (BPD) and this could occur through epigenetic programming.
      In this perspective, we aimed to determine whether childhood maltreatment could
      durably modify epigenetic processes by the means of a whole-genome methylation
      scan of BPD subjects. Using the Illumina Infinium(r) HumanMethylation450
      BeadChip, global methylation status of DNA extracted from peripheral blood
      leucocytes was correlated to the severity of childhood maltreatment in 96 BPD
      subjects suffering from a high level of child adversity and 93 subjects suffering
      from major depressive disorder (MDD) and reporting a low rate of child
      maltreatment. Several CpGs within or near the following genes (IL17RA, miR124-3,
      KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A
      and SPSB2) were found to be differently methylated, either in BPD compared with
      MDD or in relation to the severity of childhood maltreatment. A highly relevant
      biological result was observed for cg04927004 close to miR124-3 that was
      significantly associated with BPD and severity of childhood maltreatment. miR124
      3 codes for a microRNA (miRNA) targeting several genes previously found to be
      associated with BPD such as NR3C1. Our results highlight the potentially
      important role played by miRNAs in the etiology of neuropsychiatric disorders
      such as BPD and the usefulness of using methylome-wide association studies to
      uncover such candidate genes. Moreover, they offer new understanding of the
      impact of maltreatments on biological processes leading to diseases and may
      ultimately result in the identification of relevant biomarkers. 

PMID- 25612292
TI  - Dynamical signatures of collective quality grading in a social activity:
      attendance to motion pictures.
AB  - We investigate the laws governing people's decisions and interactions by studying
      the collective dynamics of a well-documented social activity for which there
      exist ample records of the perceived quality: the attendance to movie theaters in
      the US. We picture the flows of attendance as impulses or "shocks" driven by
      external factors that in turn can create new cascades of attendances through
      direct recommendations whose effectiveness depends on the perceived quality of
      the movies. This corresponds to an epidemic branching model comprised of a
      decaying exponential function determining the time between cause and action, and
      a cascade of actions triggered by previous ones. We find that the vast majority
      of the ~3,500 movies studied fit our model remarkably well. From our results, we
      are able to translate a subjective concept such as movie quality into a
      probability of the deriving individual activity, and from it we build concrete
      quantitative predictions. Our analysis opens up the possibility of understanding
      other collective dynamics for which the perceived quality or appeal of an action
      is also known. 

PMID- 25612293
TI  - Phase modulation nanoscopy: a simple approach to enhanced optical resolution.
AB  - A new modular super-resolution technique called Phase Modulation Nanoscopy
      (PhMoNa) has been developed in order to break the optical diffraction barrier in
      Confocal Laser Scanning Microscopy (LSCM). This technique is based on using
      spatially modulated illumination intensity, whilst harnessing the fluorophore's
      non-linear emission response. It allows experimental resolution in both lateral
      and axial domains to be improved by at least a factor of 2. The work is in its
      initial phase, but by using a custom built Electro Optical Modulator (EOM) in
      conjunction with functionalised Ln(III) complexes as probes, a sub-diffraction
      resolution of ~60 nm was achieved of selected cellular organelles in long term
      live cell imaging experiments.

PMID- 25612294
TI  - Brain expressed and X-linked (Bex) proteins are intrinsically disordered proteins
      (IDPs) and form new signaling hubs.
AB  - Intrinsically disordered proteins (IDPs) are abundant in complex organisms. Due
      to their promiscuous nature and their ability to adopt several conformations IDPs
      constitute important points of network regulation. The family of Brain Expressed
      and X-linked (Bex) proteins consists of 5 members in humans (Bex1-5). Recent
      reports have implicated Bex proteins in transcriptional regulation and signaling
      pathways involved in neurodegeneration, cancer, cell cycle and tumor growth.
      However, structural and biophysical data for this protein family is almost non
      existent. We used bioinformatics analyses to show that Bex proteins contain long
      regions of intrinsic disorder which are conserved across all members. Moreover,
      we confirmed the intrinsic disorder by circular dichroism spectroscopy of Bex1
      after expression and purification in E. coli. These observations strongly suggest
      that Bex proteins constitute a new group of IDPs. Based on these findings,
      together with the demonstrated promiscuity of Bex proteins and their involvement
      in different signaling pathways, we propose that Bex family members play
      important roles in the formation of protein network hubs. 

PMID- 25612296
TI  - Mortality among chemical plant workers exposed to acrylonitrile: 2011 follow-up.
AB  - OBJECTIVES: To update a cohort study of chemical workers and reevaluate lung
      cancer mortality in relation to acrylonitrile (AN) exposure. METHODS: Subjects
      were 2096 workers employed during 1955 to 2011. We identified 474 deaths through
      2011, and quantitatively estimated worker exposures to AN. Analyses included
      national and county-based standardized mortality ratios and relative risk
      regression of internal cohort rates. RESULTS: We found no statistically
      significant excess mortality risks associated with Lima employment for any cause
      of death category, including lung cancer and other cancer sites implicated in
      previous studies. CONCLUSIONS: This update provides no evidence that exposure to
      AN at levels experienced by Lima workers is associated with an increased risk of
      lung cancer mortality, as suggested in original study. Earlier reported bladder
      cancer risks decreased to a much lower, not statistically significant level.

PMID- 25612295
TI  - Endothelial nitric oxide synthase single nucleotide polymorphism and left
      ventricular function in early chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with accelerated
      cardiovascular disease and heart failure. Endothelial nitric oxide synthase
      (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been
      associated with a worse phenotype amongst patients with established heart failure
      and in patients with progression of their renal disease. The association of a
      cardiac functional difference in non-dialysis CKD patients with no known previous
      heart failure, and eNOS gene variant is investigated. METHODS: 140 non-dialysis
      CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler
      echocardiography as part of two clinical trials, were genotyped for eNOS
      Glu298Asp SNP retrospectively. RESULTS: The median estimated glomerular
      filtration rate (eGFR) was 50 mls/min and left ventricular ejection fraction
      (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were
      significant differences in LVEF across eNOS genotypes with GG genotype being
      associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%,
      TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR,
      baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol,
      high sensitive C-reactive protein, body mass index and gender) GG genotype was
      associated with a worse LVEF, and increased LV end-diastolic and systolic index
      (p = 0.004, 0.049 and 0.009 respectively). CONCLUSIONS: eNOS Glu298Asp rs1799983
      polymorphism in CKD patients is associated with relevant sub-clinical cardiac
      remodelling as detected by CMR. This gene variant may therefore represent an
      important genetic biomarker, and possibly highlight pathways for intervention, in
      these patients who are at particular risk of worsening cardiac disease as their
      renal dysfunction progresses.

PMID- 25612297
TI  - Evaluation of potential confounding by smoking in the presence of misclassified
      smoking data in a cohort study of workers exposed to acrylonitrile.
AB  - OBJECTIVES: To evaluate the extent to which lung cancer mortality risk estimates
      in relation to acrylonitrile (AN) exposure may have been confounded by smoking in
      the presence of misclassified smoking data. METHODS: Subjects were 992 white men
      employed for three or more months between 1960 and 1996 at a chemical plant in
      Lima, Ohio. We used Monte Carlo-based sensitivity analysis to address possible
      confounding by smoking. RESULTS: In Monte Carlo simulations that accounted for
      the relationship between smoking and AN exposure, mean relative risks for lung
      cancer mortality in relation to AN exposure decreased and we observed somewhat
      less evidence of an exposure-response relationship. CONCLUSIONS: Our simulations
      suggest that the relationship between AN exposure and lung cancer mortality was
      positively confounded by smoking in the original Lima cohort study.

PMID- 25612298
TI  - Catalytic nucleic acids (DNAzymes) as functional units for logic gates and
      computing circuits: from basic principles to practical applications.
AB  - This feature article addresses the implementation of catalytic nucleic acids as
      functional units for the construction of logic gates and computing circuits, and
      discusses the future applications of these systems. The assembly of computational
      modules composed of DNAzymes has led to the operation of a universal set of logic
      gates, to field programmable logic gates and computing circuits, to the
      development of multiplexers/demultiplexers, and to full-adder systems. Also,
      DNAzyme cascades operating as logic gates and computing circuits were
      demonstrated. DNAzyme logic systems find important practical applications. These
      include the use of DNAzyme-based systems for sensing and multiplexed analyses,
      for the development of controlled release and drug delivery systems, for
      regulating intracellular biosynthetic pathways, and for the programmed synthesis
      and operation of cascades. 

PMID- 25612299
TI  - Three different up-titration regimens of ponesimod, an S1P1 receptor modulator,
      in healthy subjects.
AB  - Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent
      reduction of circulating lymphocytes upon oral dosing. Previous studies showed
      that single doses up to 75 mg or multiple doses up to 40 mg once daily are well
      tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays
      upon treatment initiation are reduced by gradual up-titration to the maintenance
      dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3
      way crossover study compared the tolerability, safety, pharmacokinetics,
      cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens
      of ponesimod in healthy male and female subjects. Up-titration regimens comprised
      escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or
      both). After the third up-titration period a variable-duration washout period of
      1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod.
      Adverse events were transient and mild to moderate in intensity, not different
      between regimens. HR decrease after the first dose was greater than after all
      subsequent doses, including up-titration doses. Little or no HR change was
      observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg
      b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing
      interval. 

PMID- 25612300
TI  - Source tracking Mycobacterium ulcerans infections in the Ashanti region, Ghana.
AB  - Although several studies have associated Mycobacterium ulcerans (MU) infection,
      Buruli ulcer (BU), with slow moving water bodies, there is still no definite mode
      of transmission. Ecological and transmission studies suggest Variable Number
      Tandem Repeat (VNTR) typing as a useful tool to differentiate MU strains from
      other Mycolactone Producing Mycobacteria (MPM). Deciphering the genetic
      relatedness of clinical and environmental isolates is seminal to determining
      reservoirs, vectors and transmission routes. In this study, we attempted to
      source-track MU infections to specific water bodies by matching VNTR profiles of
      MU in human samples to those in the environment. Environmental samples were
      collected from 10 water bodies in four BU endemic communities in the Ashanti
      region, Ghana. Four VNTR loci in MU Agy99 genome, were used to genotype
      environmental MU ecovars, and those from 14 confirmed BU patients within the same
      study area. Length polymorphism was confirmed with sequencing. MU was present in
      the 3 different types of water bodies, but significantly higher in biofilm
      samples. Four MU genotypes, designated W, X, Y and Z, were typed in both human
      and environmental samples. Other reported genotypes were only found in water
      bodies. Animal trapping identified 1 mouse with lesion characteristic of BU,
      which was confirmed as MU infection. Our findings suggest that patients may have
      been infected from community associated water bodies. Further, we present
      evidence that small mammals within endemic communities could be susceptible to MU
      infections. M. ulcerans transmission could involve several routes where humans
      have contact with risk environments, which may be further compounded by water
      bodies acting as vehicles for disseminating strains. 

PMID- 25612301
TI  - Contribution of collagen fiber undulation to regional biomechanical properties
      along porcine thoracic aorta.
AB  - As major extracellular matrix components, elastin, and collagen play crucial
      roles in regulating the mechanical properties of the aortic wall and, thus, the
      normal cardiovascular function. The mechanical properties of aorta, known to vary
      with age and multitude of diseases as well as the proximity to the heart, have
      been attributed to the variations in the content and architecture of wall
      constituents. This study is focused on the role of layer-specific collagen
      undulation in the variation of mechanical properties along the porcine descending
      thoracic aorta. Planar biaxial tensile tests are performed to characterize the
      hyperelastic anisotropic mechanical behavior of tissues dissected from four
      locations along the thoracic aorta. Multiphoton microscopy is used to image the
      associated regional microstructure. Exponential-based and recruitment-based
      constitutive models are used to account for the observed mechanical behavior
      while considering the aortic wall as a composite of two layers with independent
      properties. An elevated stiffness is observed in distal regions compared to
      proximal regions of thoracic aorta, consistent with sharper and earlier collagen
      recruitment estimated for medial and adventitial layers in the models.
      Multiphoton images further support our prediction that higher stiffness in distal
      regions is associated with less undulation in collagen fibers. Recruitment-based
      models further reveal that regardless of the location, collagen in the media is
      recruited from the onset of stretching, whereas adventitial collagen starts to
      engage with a delay. A parameter sensitivity analysis is performed to
      discriminate between the models in terms of the confidence in the estimated model
      parameters. 

PMID- 25612303
TI  - Bleeding control during laparoscopic liver resection: a review of literature.
AB  - Despite the established advantages of laparoscopy, bleeding control during
      laparoscopic liver resection (LLR) is a liver-specific improvement. The 2nd
      International Consensus Conference on Laparoscopic Liver Resection was held in
      October 2014 at Morioka, Japan. One of the most capital questions was: What is
      essential in bleeding control during LLR? In order to correctly address this
      question, we conducted a comprehensive review of the literature. Essential points
      based on personal experience of the expert panel are also discussed. A total of
      54 publications were identified. Based on this analysis, the working group built
      these recommendations: (1) a pneumoperitoneum of 10-14 mmHg should be used as it
      allows a good control of the bleeding without significant modifications of
      hemodynamics; (2) a low central venous pressure (<5 mmHg) should be used; (3)
      laparoscopy facilitates inflow and outflow control; and (4) surgeons should be
      experienced with the use of all surgical devices for liver transection and should
      master laparoscopic suture before starting LLR. Precoagulation with
      radiofrequency can be useful, particularly in cases of atypical resection. These
      recommendations are mostly based on experts' opinions and on B or C quality of
      evidence grade studies. More prospective data are required to confirm these
      results.

PMID- 25612304
TI  - Human herpesvirus 8 seroconversion in a population-based cohort of men in Tobago.
AB  - Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In
      Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be
      39.9% in men with prostate cancer compared to <22.9% in healthier women and men.
      To understand HHV-8 transmission, we examined HHV-8 seroconversion and
      seroreversion, and risk factors for these changes in Tobago men. Serum specimens
      from a sub-cohort of Tobago Prostate Survey men, aged 40-81 years (n = 381/442),
      were collected at baseline and a subsequent visit between 3 and 9 years and
      tested for HHV-8 seropositivity using an immunofluorescence assay for antibodies
      against HHV-8 lytic antigens. Poisson distribution was used to calculate HHV-8
      seroconversion and seroreversion rates and their 95% confidence intervals.
      Differences in baseline characteristics between HHV-seroconverters versus
      persistent HHV-8 seronegative men and HHV-8 seroreverters versus HHV-8
      seropositive men were examined. HHV-8 seropositivity was 12.3% (N = 381) at
      baseline, with HHV-8 seropositivity significantly higher in increasing age
      groups, 40-49 (4.0%) to 70-81 (37.5%) years (P-value trend <0.0001). HHV-8
      seroconversion and seroreversion rates were 0.23 per 100 person-years (95% C.I.,
      0.06-0.58) and 2.42 per 100 person-years (95% C.I., 0.89-5.26), respectively.
      There were significantly more HHV-8 seroconverters who reported "ever smoked
      cigarettes of >6 months" at baseline compared to HHV-8 persistent seronegative
      men (P-value = 0.03). Baseline characteristics of HHV-8 seroreverters did not
      differ from persistent seropositive men. Low HHV-8 seroconversion and
      seroreversion rates were found. Data suggest that HHV-8 transmission occurred at
      earlier ages, <40 years, in Tobago men.

PMID- 25612305
TI  - Update on management of cardiac arrhythmias in acute coronary syndromes.
AB  - This review summarizes different types of arrhythmias in patients with acute
      coronary syndromes and provides an overview of the available therapeutic options
      for acute care and management of critical arrhythmias. The different therapeutic
      options are depending on the origin and type of arrhythmia. The main common
      dominant mechanisms are intramural re-entry in ischemia and triggered activity in
      reperfusion. The different forms of arrhythmia were explained in detail. Atrial
      arrhythmias are mainly atrial fibrillation; other forms are rare and usually self
      limited. As therapeutic options antiarrhythmic drug therapy with beta-blockers or
      amiodarone and direct current cardioversion are suitable. Ventricular arrhythmias
      can be divided in premature ventricular complexes, accelerated idioventricular
      rhythm, non-sustained ventricular tachycardia, sustained ventricular tachycardia
      (VT), ventricular fibrillation (VF) and electrical storm. As therapeutic options
      antiarrhythmic drug therapy, implantable cardioverter defibrillator therapy
      (ICD), radiofrequency catheter ablation (RFA) and stellate ganglion blockade are
      available. The treatment with antiarrhythmic drug is rather cautious recommended,
      with the exception of beta-blockers. An additional drug therapy with ranolazine
      may be considered. The advantage of ICD therapy for long-term primary or
      secondary prophylactic therapy has been well documented. ICD therapy is
      associated with significant reduction in mortality compared with antiarrhythmic
      drug therapy (mainly amiodarone), with the exception of beta-blockers. RFA and
      stellate ganglion blockade are rather intended as therapeutically options for
      incessant VT/VF or electrical storm. 

PMID- 25612302
TI  - Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in
      adult zebrafish brain.
AB  - Cell adhesion molecule cadherins play important roles in both development and
      maintenance of adult structures. Most studies on cadherin expression have been
      carried out in developing organisms, but information on cadherin distribution in
      adult vertebrate brains is limited. In this study we used in situ hybridization
      to examine mRNA expression of three cadherins, protocadherin-19, protocadherin
      17, and cadherin-6 in adult zebrafish brain. Each cadherin exhibits a distinct
      expression pattern in the fish brain, with protocadherin-19 and protocadherin-17
      showing much wider and stronger expression than that of cadherin-6. Both
      protocadherin-19 and protocadherin-17-expressing cells occur throughout the
      brain, with strong expression in the ventromedial telencephalon, periventricular
      regions of the thalamus and anterior hypothalamus, stratum periventriculare of
      the optic tectum, dorsal tegmental nucleus, granular regions of the cerebellar
      body and valvula, and superficial layers of the facial and vagal lobes. Numerous
      sensory structures (e.g., auditory, gustatory, lateral line, olfactory, and
      visual nuclei) and motor nuclei (e.g., oculomotor, trochlear, trigeminal motor,
      abducens, and vagal motor nuclei) contain protocadherin-19 and/or protocadherin
      17-expressing cell. Expression of these two protocadherins is similar in the
      ventromedial telencephalon, thalamus, hypothalamus, facial, and vagal lobes, but
      substantially different in the dorsolateral telencephalon, intermediate layers of
      the optic tectum, and cerebellar valvula. In contrast to the two protocadherins,
      cadherin-6 expression is much weaker and limited in the adult fish brain.

PMID- 25612306
TI  - Can Syntax Score predict angiographically visible distal embolization during
      primary percutaneous coronary intervention?
AB  - BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the most
      effective and validated treatment strategy of ST segment elevation myocardial
      infarction (STEMI). Nevertheless, normal myocardial perfusion cannot always be
      achieved at the end of the procedure in a significant number of patients with
      STEMI. The aim of this study was to investigate angiographic and procedural
      predictors of angiographically visible distal embolization (AVDE) during PPCI and
      the assessment of mid and long term mortality. METHODS: Four hundred and sixty
      five consecutive patients undergoing PPCI for acute STEMI and matching
      eligibility criteria of the study between January 2010 and December 2011 were
      enrolled in the study. Patients were divided into two groups; 61 (13.1%) with
      AVDE and 404 patients without AVDE based on angiograms performed during PPCI.
      RESULTS: Longer stent length, higher balloon diameter, low Syntax score (SxS),
      low LVEF, high neutrophil/lymphocyte ratio and chronic renal failure were seemed
      to be associated with AVDE in univariate analysis and these variables were
      entered into multivariate analysis. In multivariate analyzes, stent length, LVEF
      and low SxS were found to be associated with AVDE (OR: 1,11, 95 % CI: 1,06-1,16,
      p< 0,001; OR: 0,80, 95%CI: 0.80-0.91, p< 0,001; OR: 0,85, 95%CI: 0,79-0,91, P<
      0,001, respectively). CONCLUSIONS: This study concluded that low SxS, longer
      stent length, low LVEF were predicting risk factors associated with the
      development of AVDE in patients undergoing PPCI. Low SxS associated with AVDE may
      be linked to the strong relation between AVDE and high thrombus burden and
      composition of atherosclerotic plaque rather than complex coronary lesions.

PMID- 25612307
TI  - Comparison of an oscillometric method with cardiac magnetic resonance for the
      analysis of aortic pulse wave velocity.
AB  - OBJECTIVES: Pulse wave velocity (PWV) is the proposed gold-standard for the
      assessment of aortic elastic properties. The aim of this study was to compare
      aortic PWV determined by a recently developed oscillometric device with cardiac
      magnetic resonance imaging (CMR). METHODS: PWV was assessed in 40 volunteers with
      two different methods. The oscillometric method (PWVOSC) is based on a transfer
      function from the brachial pressure waves determined by oscillometric blood
      pressure measurements with a common cuff (Mobil-O-Graph, I.E.M. Stolberg,
      Germany). CMR was used to determine aortic PWVCMR with the use of the transit
      time method based on phase-contrast imaging at the level of the ascending and
      abdominal aorta on a clinical 1.5 Tesla scanner (Siemens, Erlangen, Germany).
      RESULTS: The median age of the study population was 34 years (IQR: 24-55 years,
      11 females). A very strong correlation was found between PWVOSC and PWVCMR (r =
      0.859, p < 0.001). Mean PWVOSC was 6.7 +/- 1.8 m/s and mean PWVCMR was 6.1 +/-
      1.8 m/s (p < 0.001). Analysis of agreement between the two measurements using
      Bland-Altman method showed a bias of 0.57 m/s (upper and lower limit of
      agreement: 2.49 m/s and -1.34 m/s). The corresponding coefficient of variation
      between both measurements was 15%. CONCLUSION: Aortic pulse wave velocity
      assessed by transformation of the brachial pressure waveform showed an acceptable
      agreement with the CMR-derived transit time method.

PMID- 25612308
TI  - A polyoxometalate-encapsulating cationic metal-organic framework as a
      heterogeneous catalyst for desulfurization.
AB  - A new cationic triazole-based metal-organic framework encapsulating Keggin-type
      polyoxometalates, with the molecular formula [Co(BBPTZ)3][HPMo12O40]?24 H2O
      [compound 1; BBPTZ = 4,4'-bis(1,2,4-triazol-1-ylmethyl)biphenyl] is
      hydrothermally synthesized and characterized by elemental analysis, IR
      spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single
      crystal X-ray diffraction. The structure of compound 1 contains a non
      interpenetrated 3D CdSO4 (cds)-type framework with two types of channels that are
      interconnected with each other; straight channels that are occupied by the Keggin
      type POM anions, and wavelike channels that contain lattice water molecules. The
      catalytic activity of compound 1 in the oxidative desulfurization reaction
      indicates that it is not only an effective and size-selective heterogeneous
      catalyst, but it also exhibits distinct structural stability in the catalytic
      reaction system.

PMID- 25612309
TI  - Myc-induced liver tumors in transgenic zebrafish can regress in tp53 null
      mutation.
AB  - Hepatocellular carcinoma (HCC) is currently one of the top lethal cancers with an
      increasing trend. Deregulation of MYC in HCC is frequently detected and always
      correlated with poor prognosis. As the zebrafish genome contains two
      differentially expressed zebrafish myc orthologs, myca and mycb, it remains
      unclear about the oncogenicity of the two zebrafish myc genes. In the present
      study, we developed two transgenic zebrafish lines to over-express myca and mycb
      respectively in the liver using a mifepristone-inducible system and found that
      both myc genes were oncogenic. Moreover, the transgenic expression of myca in
      hepatocytes caused robust liver tumors with several distinct phenotypes of
      variable severity. ~5% of myca transgenic fish developing multinodular HCC with
      cirrhosis after 8 months of induced myca expression. Apoptosis was also observed
      with myca expression; introduction of homozygous tp53(-/-) mutation into the myca
      transgenic fish reduced apoptosis and accelerated tumor progression. The
      malignant status of hepatocytes was dependent on continued expression of myca;
      withdrawal of the mifepristone inducer resulted in a rapid regression of liver
      tumors, and the tumor regression occurred even in the tp53(-/-) mutation
      background. Thus, our data demonstrated the robust oncogenicity of zebrafish myca
      and the requirement of sustained Myc overexpression for maintenance of the liver
      tumor phenotype in this transgenic model. Furthermore, tumor regression is
      independent of the function of Tp53.

PMID- 25612310
TI  - Adaptive and repeated cumulative meta-analyses of safety data during a new drug
      development process.
AB  - During a new drug development process, it is desirable to timely detect potential
      safety signals. For this purpose, repeated meta-analyses may be performed
      sequentially on accumulating safety data. Moreover, if the amount of safety data
      from the originally planned program is not enough to ensure adequate power to
      test a specific hypothesis (e.g., the noninferiority hypothesis of an event of
      interest), the total sample size may be increased by adding new studies to the
      program. Without appropriate adjustment, it is well known that the type I error
      rate will be inflated because of repeated analyses and sample size adjustment. In
      this paper, we discuss potential issues associated with adaptive and repeated
      cumulative meta-analyses of safety data conducted during a drug development
      process. We consider both frequentist and Bayesian approaches. A new drug
      development example is used to demonstrate the application of the methods.

PMID- 25612311
TI  - Determination of factors associated with natural soil suppressivity to potato
      common scab.
AB  - Common scab of potatoes is a disease, which is difficult to manage due to complex
      interactions of the pathogenic bacteria (Streptomyces spp.) with soil, microbial
      community and potato plants. In Bohemian-Moravian Highlands in the Czech Republic
      two sites (Vyklantice and Zdirec) were selected for a study of common scab
      disease suppressivity. At both sites, a field with low disease severity occurs
      next to one with high severity and the situation was regularly observed over four
      decades although all four fields undergo a crop rotation. In the four fields,
      quantities of bacteria, actinobacteria and the gene txtB from the biosynthetic
      gene cluster of thaxtomin, the main pathogenicity factor of common scab, were
      analyzed by real-time PCR. Microbial community structure was compared by terminal
      fragment length polymorphism analysis. Soil and potato periderm were
      characterized by contents of carbon, nitrogen, phosphorus, sulphur, calcium,
      magnesium, and iron. Quality of organic matter was assessed by high performance
      liquid chromatography of soil extracts. The study demonstrated that the
      suppressive character of the fields is locally specific. At Zdirec, the
      suppressivity was associated with low txtB gene copies in bulk soil, while at
      Vyklantice site it was associated with low txtB gene copies in the tuberosphere.
      The differences were discussed with respect to the effect of abiotic conditions
      at Zdirec and interaction between potato plant and soil microbial community at
      Vyklantice. Soil pH, Ca soil content or cation concentrations, although different
      were not in the range to predict the disease severity. Low severity of common
      scab was associated with low content of soil C, N, C/N, Ca and Fe suggesting that
      oligotrophic conditions may be favorable to common scab suppression.

PMID- 25612312
TI  - The influence of HIV and schistosomiasis on renal function: a cross-sectional
      study among children at a hospital in Tanzania.
AB  - BACKGROUND: Schistosomiasis and HIV are both associated with kidney disease.
      Prevalence and factors associated with abnormal renal function among HIV-infected
      children in Africa compared to uninfected controls have not been well described
      in a schistosomiasis endemic area. METHODOLOGY/PRINCIPAL FINDINGS: This cross
      sectional study was conducted at the Sekou Toure Regional Hospital HIV clinic in
      Mwanza, Tanzania. A total of 122 HIV-infected children and 122 HIV-uninfected
      siblings were consecutively enrolled. Fresh urine was obtained for measurement of
      albuminuria and Schistosoma circulating cathodic antigen. Blood was collected for
      measurement of serum creatinine. Estimated glomerular filtration rate (eGFR) was
      calculated using the modified Schwartz equation. Renal dysfunction was defined
      operationally as eGFR<60 mL/min/1.73 m2 and/or albuminuria>20 mg/L in a single
      sample. Among 122 HIV-infected children, 61/122 (50.0%) met our criteria for
      renal dysfunction: 54/122 (44.3%) had albuminuria>20 mg/L and 9/122 (7.4%) had
      eGFR<60. Among 122 HIV-uninfected children, 51/122 (41.8%) met our criteria for
      renal dysfunction: 48/122 (39.3%) had albuminuria>20 mg/L and 6/122 (4.9%) had
      eGFR<60. Schistosomiasis was the only factor significantly associated with renal
      dysfunction by multivariable logistic regression (OR = 2.51, 95% CI 1.46-4.31, p
      = 0.001). CONCLUSIONS/SIGNIFICANCE: A high prevalence of renal dysfunction exists
      among both HIV-infected Tanzanian children and their HIV-uninfected siblings.
      Schistosomiasis was strongly associated with renal dysfunction.

PMID- 25612313
TI  - A comparative study of graphene-hydrogel hybrid bionanocomposites for biosensing.
AB  - Hydrogels have become increasingly popular as immobilization materials for cells,
      enzymes and proteins for biosensing applications. Enzymatic biosensors that
      utilize hydrogel as an encapsulant have shown improvements over other
      immobilization techniques such as cross linking and covalent bonding. However, to
      date there are no studies which directly compare multiple hydrogel-graphene
      nanocomposites using the same enzyme and test conditions. This study compares the
      performance of four different hydrogels used as protein encapsulants in a
      mediator-free biosensor based on graphene-nanometal-enzyme composites. Alcohol
      oxidase (AOx) was encapsulated in chitosan poly-N-isopropylacrylamide (PNIPAAM),
      silk fibroin or cellulose nanocrystals (CNC) hydrogels, and then spin coated onto
      a nanoplatinum-graphene modified electrode. The transduction mechanism for the
      biosensor was based on AOx-catalyzed oxidation of methanol to produce hydrogen
      peroxide. To isolate the effect(s) of stimulus response on biosensor behavior,
      all experiments were conducted at 25  degrees C and pH 7.10. Electroactive
      surface area (ESA), electrochemical impedance spectroscopy (EIS), sensitivity to
      methanol, response time, limit of detection, and shelf life were measured for
      each bionanocomposite. Chitosan and PNIPAAM had the highest sensitivity (0.46 +/-
      0.2 and 0.3 +/- 0.1 MUA mM(-1), respectively) and electroactive surface area (0.2
      +/- 0.06 and 0.2 +/- 0.02 cm(2), respectively), as well as the fastest response
      time (4.3 +/- 0.8 and 4.8 +/- 1.1 s, respectively). Silk and CNC demonstrated
      lower sensitivity (0.09 +/- 0.02 and 0.15 +/- 0.03 MUA mM(-1), respectively),
      lower electroactive surface area (0.12 +/- 0.02 and 0.09 +/- 0.03 cm(2),
      respectively), and longer response time (8.9 +/- 2.1 and 6.3 +/- 0.8 s,
      respectively). The high porosity of chitosan, PNIPAAM, and silk gels led to
      excellent transport, which was significantly better than CNC bionanocomposites.
      Electrochemical performance of CNC bionanocomposites were relatively poor, which
      may be linked to poor gel stability. The differences between the Chitosan/PNIPAAM
      group and the Silk/CNC group were statistically significant (p < 0.05) based on
      ANOVA. Each of these composites was within the range of other published devices
      in the literature, while some attributes were significantly improved (namely
      response time and shelf life). The main advantages of these hydrogel composites
      over other devices is that only one enzyme is required, all materials are non
      toxic, the sensor does not require mediators/cofactors, and the shelf life and
      response time are significantly improved over other devices. 

PMID- 25612314
TI  - Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and
      a NHE10-specific monoclonal antibody.
AB  - The functions of Na(+) /H(+) exchangers (NHEs) during osteoclastic
      differentiation were investigated using the NHE inhibitor amiloride and a
      monoclonal antibody (MAb). Compared with sRANKL-stimulated control cells,
      amiloride decreased the number of large TRAP-positive osteoclast cells (OCs) with
      >=10 nuclei and increased the number of small TRAP-positive OCs with <=10 nuclei
      during sRANKL-dependent osteoclastic differentiation of RAW264.7 cells. NHE10
      mRNA expression and OC differentiation markers were increased by sRANKL
      stimulation in dose- and time-dependent manners. NHEs 1-9 mRNA expression was not
      increased by sRANKL stimulation. Similar to amiloride, a rat anti-mouse NHE10 MAb
      (clone 6B11) decreased the number of large TRAP-positive OCs, but increased the
      number of small TRAP-positive OCs. These findings suggested that inhibition of
      NHEs by amiloride or an anti-NHE10 MAb prevented sRANKL-promoted cellular fusion.
      The anti-NHE10 MAb has the potential for use as an effective inhibitor of bone
      resorption for targeted bone disease therapy. 

PMID- 25612315
TI  - Boric acid destabilizes the hyphal cytoskeleton and inhibits invasive growth of
      Candida albicans.
AB  - Exposure of Candida albicans to sub-lethal concentrations of boric acid (BA)
      restricts the dimorphic fungus to its yeast morphology and prevents the formation
      of invasive hyphae on solid substrates. Exposure to BA causes a rapid and
      reversible disappearance of polarisome and Spitzenkorper in growing hyphae. In BA
      treated hyphae of C. albicans, actin quickly reorganizes from cytoplasmic cables
      to cortical patches and cell wall growth switches from an apical to an isotropic
      pattern. As a result of the cytoskeletal changes, the hyphal tips broaden and
      directional growth of hyphae ceases in the presence of BA. An analysis of
      homozygous deletion strains showed that mutants with constitutive or enhanced
      hyphal growth (tup1, nrg1, ssn6, rbf1) are BA-sensitive, demonstrating that
      cellular morphology is a major determinant of BA tolerance. The screening of
      deletion mutants also showed that deficiencies of the main activator of hyphal
      gene expression, Efg1, and the Rim101-signalling cascade, leading to Efg1
      activation, cause BA resistance. Taken together, the data presented show that the
      selective inhibitory effect on BA on C. albicans hyphae is rooted in a disruption
      of apical cytoskeletal elements of growing hyphae.

PMID- 25612316
TI  - Correction.

PMID- 25612317
TI  - Height and bone mineral density are associated with naevus count supporting the
      importance of growth in melanoma susceptibility.
AB  - Naevus count is the strongest risk factor for melanoma. Body Mass Index (BMI) has
      been linked to melanoma risk. In this study, we investigate the link between
      naevus count and height, weight and bone mineral density (BMD) in the TwinsUK
      cohort (N = 2119). In addition we adjusted for leucocyte telomere length (LTL) as
      LTL is linked to both BMD and naevus count. Naevus count was positively
      associated with height (p = 0.001) but not with weight (p = 0.187) despite
      adjusting for age and twin relatedness. This suggests that the previously
      reported melanoma association with BMI may be explained by height alone. Further
      adjustment for LTL did not affect the significance of the association between
      height and naevus count so LTL does not fully explain these results. BMD was
      associated with naevus count at the spine (coeff 18.9, p = 0.01), hip (coeff =
      18.9, p = 0.03) and forearm (coeff = 32.7, p = 0.06) despite adjusting for age,
      twin relatedness, weight, height and LTL. This large study in healthy individuals
      shows that growth via height, probably in early life, and bone mass are risk
      factors for melanoma via increased naevus count. The link between these two
      phenotypes may possibly be explained by telomere biology, differentiation genes
      from the neural crests but also other yet unknown factors which may influence
      both bones and melanocytes biology.

PMID- 25612318
TI  - BILL-cadherin/cadherin-17 contributes to the survival of memory B cells.
AB  - Memory B cells (MBCs) and long-lived plasma cells (LLPCs) are responsible for
      immunological "memory", which can last for many years. The long-term survival
      niche for LLPCs in the bone marrow is well characterized; however, the
      corresponding niche for MBCs is unclear. BILL-cadherin/cadherin-17 (CDH17) is the
      only member of the cadherin superfamily that is expressed on mouse B lymphocytes
      in a spatiotemporally regulated manner. Here, we show that half of all MBCs
      regain expression of CDH17 during the later stage of development. The maintenance
      of high affinity antigen-specific serum antibodies was impaired in CDH17(-/-)
      mice and the number of antigen-specific MBCs was reduced as compared to wild-type
      mice (WT). Also, specific responses to secondary antigens were ablated in CDH17(
      /-) mice, whereas primary antibody responses were the same as those in WT mice.
      Cell cycle analysis revealed a decline in the proliferation of CDH17(-) MBCs as
      compared to CDH17(+) MBCs. In addition, we identified a subpopulation of splenic
      stromal cells, MAdCAM-1(+) blood endothelial cells (BEC), which was CDH17(+).
      Taken together, these results suggest that CDH17 plays a role in the long-term
      survival of MBCs, presumably via an "MBC niche" comprising, at least in part, BEC
      in the spleen.

PMID- 25612319
TI  - IQM: an extensible and portable open source application for image and signal
      analysis in Java.
AB  - Image and signal analysis applications are substantial in scientific research.
      Both open source and commercial packages provide a wide range of functions for
      image and signal analysis, which are sometimes supported very well by the
      communities in the corresponding fields. Commercial software packages have the
      major drawback of being expensive and having undisclosed source code, which
      hampers extending the functionality if there is no plugin interface or similar
      option available. However, both variants cannot cover all possible use cases and
      sometimes custom developments are unavoidable, requiring open source
      applications. In this paper we describe IQM, a completely free, portable and open
      source (GNU GPLv3) image and signal analysis application written in pure Java.
      IQM does not depend on any natively installed libraries and is therefore runnable
      out-of-the-box. Currently, a continuously growing repertoire of 50 image and 16
      signal analysis algorithms is provided. The modular functional architecture based
      on the three-tier model is described along the most important functionality.
      Extensibility is achieved using operator plugins, and the development of more
      complex workflows is provided by a Groovy script interface to the JVM. We
      demonstrate IQM's image and signal processing capabilities in a proof-of
      principle analysis and provide example implementations to illustrate the plugin
      framework and the scripting interface. IQM integrates with the popular ImageJ
      image processing software and is aiming at complementing functionality rather
      than competing with existing open source software. Machine learning can be
      integrated into more complex algorithms via the WEKA software package as well,
      enabling the development of transparent and robust methods for image and signal
      analysis. 

PMID- 25612320
TI  - International engagement by United States academic neurology departments: A
      national survey.

PMID- 25612321
TI  - Novel findings of fetal ectopic atrial tachycardia by cardiotocography.

PMID- 25612323
TI  - Genomics of HIV infection.

PMID- 25612322
TI  - Application of gene-editing technologies to HIV-1.
AB  - PURPOSE OF REVIEW: This review will highlight some of the recent advances in
      genome engineering with applications for both clinical and basic science
      investigations of HIV-1. RECENT FINDINGS: Over the last year, the field of HIV
      cure research has seen major breakthroughs with the success of the first phase I
      clinical trial involving gene editing of CCR5 in patient-derived CD4(+) T cells.
      This first human use of gene-editing technology was accomplished using zinc
      finger nucleases (ZFNs). Zinc finger nucleases and the advent of additional tools
      for genome engineering, including transcription activator-like effector nucleases
      (TALENS) and the clustered regularly interspaced short palindromic repeat
      (CRISPR)/Cas9 system, have made gene editing remarkably simple and affordable.
      Here we will discuss the different gene-editing technologies, the use of gene
      editing in HIV research over the past year, and potential applications of gene
      editing for both in-vitro and in-vivo studies. SUMMARY: Genome-engineering
      technologies have rapidly progressed over the past few years such that these
      systems can be easily applied in any laboratory for a variety of purposes. For
      HIV-1, upcoming clinical trials will determine if gene editing can provide the
      long-awaited functional cure. In addition, manipulation of host genomes, whether
      in vivo or in vitro, can facilitate development of better animal models and
      culture methods for studying HIV-1 transmission, pathogenesis, and virus-host
      interactions.

PMID- 25612324
TI  - Functionalization of liquid-exfoliated two-dimensional 2H-MoS2.
AB  - Layered two-dimensional (2D) inorganic transition-metal dichalchogenides (TMDs)
      have attracted great interest as a result of their potential application in
      optoelectronics, catalysis, and medicine. However, methods to functionalize and
      process such 2D TMDs remain scarce. We have established a facile route towards
      functionalized layered MoS2 . We found that the reaction of liquid-exfoliated 2D
      MoS2 , with M(OAc)2 salts (M=Ni, Cu, Zn; OAc=acetate) yielded functionalized MoS2
      -M(OAc)2 materials. Importantly, this method furnished the 2H-polytype of MoS2
      which is a semiconductor. X-ray photoelectron spectroscopy (XPS), diffuse
      reflectance infrared Fourier transform spectroscopy (DRIFT-IR), and
      thermogravimetric analysis (TGA) provide strong evidence for the coordination of
      MoS2 surface sulfur atoms to the M(OAc)2 salt. Interestingly, functionalization
      of 2H-MoS2 allows for its dispersion/processing in more conventional laboratory
      solvents. 

PMID- 25612326
TI  - Cluster-based comparison of the peptide mass fingerprint obtained by MALDI-TOF
      mass spectrometry. A case study: long-term stability of rituximab.
AB  - We evaluated the use of the peptide mass fingerprint (PMF) obtained by matrix
      assisted laser desorption and ionization (MALDI) time-of-flight mass spectrometry
      (TOF-MS) to track changes in the structure of a protein. The first problem we had
      to overcome was the inherent complexity of the PMF, which makes it difficult to
      compare. We dealt with this problem by developing a cluster-based comparison
      algorithm which takes into account the proportional error made by the mass
      spectrometer. This procedure involves grouping together similar masses in an
      intelligent manner, so that we can determine which data correspond to the same
      peptide (any slight differences can be explained as experimental errors), and
      which of them are too different and thus more likely to represent different
      peptides. The proposed algorithm was applied to track changes in a commercially
      available monoclonal antibody (mAb), namely rituximab (RTX), prepared under the
      usual hospital conditions and stored refrigerated (4  degrees C) and frozen (-20 
      degrees C) for a long term study. PMFs were obtained periodically over three
      months. For each checked time, five replicates of the PMFs were obtained in order
      to evaluate the similarities between them by means of the occurrences of the
      particular peptides (m/z). After applying the algorithm to the PMF, different
      approaches were used to analyse the results. Surprisingly, all of them suggested
      that there were no differences between the two storage conditions tested, i.e.
      the RTX samples were almost equally well preserved when stored refrigerated at 4 
      degrees C or frozen at -20  degrees C. The cluster-based methodology is new in
      protein mass spectrometry and could be useful as an easy test for major changes
      in proteins and biopharmaceutics for diverse applications in industry and other
      fields, and could provide additional stability data in relation to the practical
      use of anticancer drugs. 

PMID- 25612325
TI  - Multimodality imaging of coiled-coil mediated self-assembly in a "drug-free"
      therapeutic system.
AB  - Two complementary coiled-coil peptides CCE/CCK are used to develop a "drug free"
      therapeutic system, which can specifically kill cancer cells without a drug. CCE
      is attached to the Fab' fragment of anti-CD20 1F5 antibody (Fab'-CCE), and CCK is
      conjugated in multiple grafts to poly[N-(2-hydroxypropyl)methacrylamide] (P
      (CCK)x ). Two conjugates are consecutively administered: First, Fab'-CCE coats
      peptide CCE at CD20 antigen of lymphoma cell surface; second, CCE/CCK
      biorecognition between Fab'-CCE and P-(CCK)x leads to coiled-coil formation, CD20
      crosslinking, membrane reorganization, and ultimately cell apoptosis. To prove
      that two conjugates can assemble at cell surface, multiple fluorescence imaging
      studies are performed, including 2-channel FMT, 3D confocal microscopy, and 4
      color FACS. Confocal microscopy shows colocalization of two fluorescently labeled
      conjugates on non-Hodgkin's lymphoma (NHL) Raji cell surface, indicating "two
      step" targeting specificity. The fluorescent images also reveal that these two
      conjugates can disrupt normal membrane lipid distribution and form lipid raft
      clusters, leading to cancer cell apoptosis. This "two-step" biorecognition
      capacity is further demonstrated in a NHL xenograft model, using fluorescent
      images at whole-body, tissue and cell levels. It is also found that delaying
      injection of P-(CCK)x can significantly enhance targeting efficacy. This high
      specificity therapeutics provide a safe option to treat NHL and other B cell
      malignancies. 

PMID- 25612327
TI  - New analytical method for the study of metabolism of swertiamarin in rats after
      oral administration by UPLC-TOF-MS following DNPH derivatization.
AB  - The metabolism of swertiamarin in vivo was studied by LC-MS following 2,4
      dinitrophenylhydrazine derivatization. The ionization efficiency of the main
      metabolite erythrocentaurin was greatly enhanced by the new analytical method
      developed, and erythrocentaurin was successfully detected for the first time in
      rat plasma after oral administration of swertiamarin. Methyl 4-formylbenzoate was
      used as the internal standard to quantify erythrocentaurin in rat plasma in
      negative mode by UPLC-TOF-MS, and it was found that erythrocentaurin reached the
      maximum mean plasma concentration of 425.8 +/- 127.6 ng/mL at about 2 h after
      oral administration of swertiamarin at a dose of 200 mg/kg. A metabolic pathway
      of swertiamarin to erythrocentaurin was proposed. Swertiamarin is first
      hydrolyzed by bacterial beta-glucusidase to give the aglycone, which is readily
      converted to erythrocentaurin. The monoterpene compound swertiamarin was found to
      be metabolized to dihydroisocoumarin and alkaloid compounds in vivo, which may be
      responsible for the pharmacological effect of swertiamarin. The results may shed
      light on the clinical efficacy of swertiamarin and the new analytical method may
      assist in studies for the metabolism of other natural iridoids and secoiridoids
      in vivo.

PMID- 25612328
TI  - Highly Porous 3D Fibrous Nanostructured Bioplolymer Films with Stimuli-Responsive
      Porosity via Phase Separation in Polymer Blend.
AB  - The article describes a novel polymer blend system that yields thin films with
      unique porous nanoscale morphologies and environmentally responsive properties.
      The blend consists of sodium alginate and amine end-terminated PEG, which
      undergoes phase separation during film deposition. The blend films can be readily
      converted into highly porous membranes using facile treatment with a solution
      containing divalent ions. The resulting membranes are primarily comprised of
      alginate hydrogel, whereas the PEG phase is removed from the films during
      exposure to the saline solution, yielding nanometer-sized pores. The alginate gel
      phase forms a three-dimensional nanostructure which can be best described as a
      filament or fibrous network. Because such network geometry is untypical of
      polymer blends in thin films, possible reasons for the observed phase morphology
      are discussed. Because of ionizable carboxyl groups, the hydrogel membranes
      demonstrate responsive behavior, in particular a drastic change in their porosity
      between a highly porous state and a state with completely closed pores in
      response to changes in the solution pH. The pore-size tunability can be explored
      in multiple applications where the regulation of material's permeability is
      needed. 

PMID- 25612329
TI  - [The shoemaker and the supports].

PMID- 25612330
TI  - Incorporating dental sleep medicine into a practice: avoiding the "7 deadly
      sins".

PMID- 25612331
TI  - The effect of prophylactic powders on the surface roughness of enamel.
AB  - OBJECTIVE: To assess the effect of dental prophylactic methods on the surface
      roughness of enamel. METHODS: Enamel specimens (150) were sectioned from human
      molars and mounted on resin bases. This work consisted of two parts. In the
      first, there were eight groups (n = 15). Three groups were treated with two air
      polishing devices (AP)-LM-ProPower AirLED (Mode 1 and 2) and EMS Air-Flow Handy 2
      for 30 seconds and sodium bicarbonate prophylactic powder, and three other groups
      were treated with the two air-polishing devices using microsphere calcium
      carbonate prophylactic powder. The seventh group was treated with rubber-cup
      polishing using medium and fine grits (Oral-B prophy paste), and the eighth
      (control) was enamel with no surface treatment. In the second part of the work,
      two groups (n = 15) were subjected to treatment with the LM unit (Mode 2) and
      each of the abrasive powders for 5 seconds. Surface roughness (Ra) of samples was
      assessed using a mechanical stylus profilometer and scanning electron microscope
      (SEM). Statistical analysis of the data was conducted using two-way ANOVA and
      Tukey HSD (honest significant difference) rank order test at P = 0.05. RESULTS:
      Both prophylactic methods resulted in a statistically significant increase in
      surface roughness (P < 0.05) when compared to untreated specimens. All air
      abrasive treatments for 30 seconds resulted in an increase in roughness compared
      to rubber-cup prophylaxis (P < 0.05). However, AP with calcium carbonate and the
      sodium bicarbonate for 5 seconds produced results that were not significantly
      different from rubber-cup prophylaxis (P > 0.05). CONCLUSION: Both types of
      prophylactic dental cleaning have an effect on surface roughness. The
      abrasiveness of APs depends upon the length of treatment and the type of powder
      used.

PMID- 25612333
TI  - Guidance issued on Ebola exposure in pets.

PMID- 25612332
TI  - Retraction notice to Same sex acts involving older men. An  ethnographic study.
      Journal of Aging Studies 27 (2013) 121-134.

PMID- 25612334
TI  - Resolutions cover transport of research animals, governance.

PMID- 25612335
TI  - California shuts down   nonveterinary teeth cleaning   operation.

PMID- 25612336
TI  - More than half of pet owners   do not seek pet dental care.

PMID- 25612337
TI  - The toll it takes   to earn a veterinary degree.

PMID- 25612338
TI  - Prevention of performance-related musculoskeletal disorders.

PMID- 25612339
TI  - [The occurrence of agranulocytosis due to antithyroid drugs in a cohort of
      patients with Graves disease treated with radioactive iodine 131I during 14
      years].

PMID- 25612340
TI  - [Czech TAVI Registry. Do we need registeries?].

PMID- 25612341
TI  - [The therapy in obese diabetic type 2 patients].

PMID- 25612342
TI  - [The current statement of the Czech Society of Hypertension for the performance
      of renal denervation in resistant hypertension].

PMID- 25612344
TI  - [Internal medicine and atherosclerosis: more differences or connections?].

PMID- 25612343
TI  - [On surgery of the thoracic wall and diaphragm.1].

PMID- 25612345
TI  - [Physician must grow for preventive medicine. Interview with Prof. Hana
      Rosolova].

PMID- 25612347
TI  - [My technique. Unifocalization surgery in hypoplasia of the major pulmonary
      artery].

PMID- 25612346
TI  - [Empagliflozin: another of silent revolutioners].

PMID- 25612348
TI  - [Efficacy and safety of insulin lispro in obese patients with type 2 diabetes
      mellitus: a retrospective metaanalysis of 7 randomized controlled trials].

PMID- 25612349
TI  - Every nurse is a mental health nurse.

PMID- 25612350
TI  - NZNO resources help members make election-day decisions.

PMID- 25612351
TI  - Begging for a nursing job.

PMID- 25612352
TI  - Te Runanga conference inspires.

PMID- 25612353
TI  - Providing humanistic care.

PMID- 25612354
TI  - The Kaiwhakahaere comments.

PMID- 25612356
TI  - Health funding myths 'damaging'--senior doctors.

PMID- 25612355
TI  - Improving physical health for those with a mental illness.

PMID- 25612357
TI  - District nurses work with GPs.

PMID- 25612358
TI  - Aged-care funding boost not enough for pay parity.

PMID- 25612359
TI  - EN diploma review.

PMID- 25612360
TI  - ENs to administer IV meds.

PMID- 25612361
TI  - New process for competence reviews.

PMID- 25612362
TI  - Caring for whanau health is 'a political act'.

PMID- 25612363
TI  - Maori health inequalities and unmet needs persist.

PMID- 25612365
TI  - Game helps adolescents with depression.

PMID- 25612364
TI  - Understanding rural health.

PMID- 25612366
TI  - Improving mental health in prisons.

PMID- 25612367
TI  - Fronting up to the Francis inquiry.

PMID- 25612368
TI  - Responding to rural mental health needs.

PMID- 25612369
TI  - Acknowledging reciprocal vulnerability.

PMID- 25612370
TI  - Investigating diabetes and depression.

PMID- 25612371
TI  - Lessons learned from the coroner's court.

PMID- 25612372
TI  - Contagion and the value of resistance.

PMID- 25612373
TI  - Envisaging a new reality for Maori.

PMID- 25612374
TI  - Learning new songs, reclaiming old language.

PMID- 25612375
TI  - Turning around Maori health statistics.

PMID- 25612376
TI  - Model could reduce seclusion rates.

PMID- 25612377
TI  - A new mental health 'app' should help improve care.

PMID- 25612378
TI  - Understanding the Code.

PMID- 25612379
TI  - Professionally yours.

PMID- 25612380
TI  - Democracy is important--get involved.

PMID- 25612381
TI  - Primary health care: living better, caring more.

PMID- 25612382
TI  - Gerontology nursing: focus on end-of-life care.

PMID- 25612383
TI  - Respiratory nurses: section to review its skills framework.

PMID- 25612384
TI  - Aged Care: significant settlements ratified.

PMID- 25612385
TI  - Lasting disadvantage? Comparing career trajectories of matched temporary and
      permanent workers in Canada.
AB  - Is the economic insecurity associated with temporary employment transitory or
      lasting? What accounts for differences in medium-run earnings trajectories for
      workers first observed in temporary and permanent jobs? Although there is now a
      considerable body of research investigating mobility outcomes for temporary
      workers, most studies focus on single transition points and pay little attention
      to the quality of subsequent employment beyond its temporary or permanent status.
      In this paper, we compare income trajectories for a nationally representative
      sample of Canadian temporary workers and a set of permanent workers selected to
      match them as closely as possible on personal, job, and work-history
      characteristics. We find that temporary workers start out with lower incomes and
      fail to catch up to their permanent counterparts over the next five years.
      Differences are more pronounced for women.

PMID- 25612386
TI  - Sincere but naive: methodological queries concerning the British Columbia
      polygamy reference trial.
AB  - Academics frequently serve as expert witnesses in legal cases, yet their role as
      transmitters of social scientific knowledge remains under-examined. The present
      study analyzes the deployment of social science within British Columbia's
      polygamy reference trial where research is used to support the assertion that
      polygamy is inherently harmful to society. Within the trial record and the
      written decision, the protection of monogamy as an institution is performed in
      part through the marginalization of qualitative methodology and the concurrent
      privileging of quantitative studies that purportedly demonstrate widespread
      social harms associated with the practice of polygyny.

PMID- 25612387
TI  - In control or fatalistically ruled? The sense of mastery among working Canadians.
AB  - Using data from a 2011 nationally representative sample of Canadian workers (N =
      5,576), the present study evaluates the social-structural determinants of the
      sense of mastery. Three main contributions emerge. First, we document that each
      of the main components of socioeconomic status--education, income, occupation,
      and economic hardship--have distinct total, indirect, and net associations with
      mastery. The well-educated report more mastery because of their higher earnings-
      but exposure to more role blurring and work-family conflict offset what would
      otherwise be their even higher levels of mastery. Second, job-related demands and
      resources have largely independent associations with mastery, but our analyses
      also reveal some key areas of overlap. Third, role-blurring activities--and their
      connections with work-to-family conflict and family-to-work conflict--offer
      unique expansions to the overall narrative of mastery, with unexpected
      explanatory and suppression effects. We interpret each of these observations in
      an effort to advance recent theoretical perspectives about mastery.

PMID- 25612388
TI  - Attachment to community and civic and political engagement: a case study of
      students.
AB  - Youth's low level of civic and political engagement may detrimentally affect the
      health of communities and the democratic system. This paper examines the role of
      community attachment in explaining youth's levels of civic and engagement. This
      examination requires an evaluation of existing measures of community attachment
      and their relevance for understanding youth's experiences. The paper uses a
      student sample, highlighting a group of youth who have a degree of variation in
      their experiences of community attachment. We find that subjective measures of
      community attachment are related to volunteering and voting, but the objective
      measure of community attachment, that is, years of residence, affects voting and
      not volunteering. Different mechanisms explain civic engagement versus political
      engagement. As such, different strategies are required to combat low levels of
      civic versus political engagement.

PMID- 25612389
TI  - How to commit Canadian sociology, or "what would Innis do"?

PMID- 25612390
TI  - A distinctive Canadian sociology?

PMID- 25612391
TI  - Canadian uniqueness and theoretical-methodological pluralism in sociology.

PMID- 25612393
TI  - Comment on political sociology today: and you may ask yourself: where does that
      highway go?

PMID- 25612392
TI  - Committing more Canadian sociology: response to the comments on "Committing
      Canadian sociology".

PMID- 25612394
TI  - The status of HBCU nursing students.

PMID- 25612395
TI  - Psychometric evaluations of the efficacy expectations and Outcome Expectations
      for Exercise Scales in African American women.
AB  - This secondary analysis tested the reliability and validity of the Self-Efficacy
      for Exercise (SEE) and the Outcome Expectations for Exercise (OEE) scales in 126
      community dwelling, middle aged African American women. Social Cognitive Theory
      postulates self-efficacy is behavior age, gender and culture specific. Therefore,
      it is important to determine ifself-efficacy scales developed and tested in older
      Caucasian female adults are reliable and valid in middle aged, minority women.
      Cronbach's alpha and construct validity using hypothesis testing and confirmatory
      factor analysis supported the reliability and validity of the SEE and OEE scales
      in community dwelling, middle aged African American women.

PMID- 25612396
TI  - Transitioning RN to BSN students from acute care to hospice care nursing.
AB  - Today, most medical professionals focus on a cure. However, hospice care provides
      a quality of life for those persons nearing the end of life or persons
      experiencing a life-limiting illness. The distressing reality is that most nurses
      are not taught the full scope of end of life care (EOL) in schools of nursing.
      Because of this educational deficit, a variance in care is created that may
      adversely affect the dying patient and family's wishes. In our RN to BSN program,
      we established a partnership with a national hospice organization to provide (1)
      leadership in end-of-life course development, (2) lecturers experienced in
      hospice and palliative care, (3) field placement for students with hospice
      nurses, and (4) nursing scholarships to complete the bachelor's degree. The end
      result of this partnership is to educate registered nurses about hospice and
      palliative care, as well as to increase the nursing workforce in this area.

PMID- 25612397
TI  - Characteristics of racism and the health consequences experienced by black
      nursing faculty.
AB  - Few studies have examined the health consequences of racism experienced by Black
      nursing professors. A cohort of nine Black nursing professors at various academic
      ranks responded to a series of questions on racism, coping and intervention
      strategies to reduce the harmful health consequences. Findings identified
      behavioral characteristics of racism, resiliency factors of coping, and suggested
      workshops to minimize the effects of racism within the nursing profession.
      Implications include workshops on critical self reflection and rules of
      engagement. A question raised for future research "how to create a
      racially/ethnic inclusive and psychosocial healthy academic work environment"?

PMID- 25612398
TI  - African American women share 'real talk' stories about fatigue related to breast
      cancer treatment.
AB  - Fatigue is the most common side effect experienced by women undergoing treatment
      for breast cancer. The fatigue experience of African American (AA) women who
      undergo breast cancer treatment has been understudied. The purpose of this
      qualitative exploratory study is to share stories of 10 AA women who experienced
      fatigue related to breast cancer treatment. AA women provided real talk
      descriptors of fatigue. Women expressed how physicians were supportive of their
      exercising to manage their fatigue. However, many women describe the medications
      prescribed for fatigue as not very helpful or even making them feel worse. Women
      shared use of complementary treatment approaches and that their physicians
      approved of such complementary treatment use. All the participants described how
      they relied on prayer for their spiritual strength to deal with the overwhelming
      effects of fatigue on their daily lives. An understanding by health care
      practitioners of the fatigue and coping experiences related to breast cancer
      among AA women can provide better ways for health care practitioners to treat and
      help their AA patients address fatigue symptoms.

PMID- 25612399
TI  - Enhancing conflict competency.
AB  - PURPOSE: Professional nurses are taking on leadership roles of diverse healthcare
      teams. Development of conflict competence is essential, yet requires self
      awareness and deliberate effort. Heightened awareness of one's preferred conflict
      style and cognizance of the implications of overuse and/or underuse of these
      styles is important. DESIGN/METHODOLOGICAL APPROACH: A pre-post survey design (N
      = 14) used paired sample T-test. Paired sample correlations and an overview of
      the paired sample test are reported. FINDINGS: Students gained self-awareness
      about their preferred conflict style, recognized that each conflict style has its
      utility depending on any given situation, and demonstrated a difference in their
      most frequently used style. CONCLUSION: Limited data conveys conflict behavior
      styles among pre-licensure nursing; however, students can influence their own
      environments (either causing or fueling situations) by their personal conflict
      handling styles. Early development of these skills can raise awareness and
      cultivate ease in the management of conflict within varied settings.

PMID- 25612400
TI  - Health visitor. Briefing published by NICE.

PMID- 25612401
TI  - Scotland's chief nursing officer to step down.

PMID- 25612402
TI  - Protest as nursing and midwifery council votes to increase registration fee.

PMID- 25612404
TI  - Ebola virus guidance released for NHS primary care settings.

PMID- 25612403
TI  - Charter for early childhood published.

PMID- 25612405
TI  - Len McCluskey: NHS 'will be safe in Labour's hands.

PMID- 25612406
TI  - 'Improvements needed' in pregnancy care for women with diabetes.

PMID- 25612407
TI  - Substance misuse support for families in Scotland.

PMID- 25612408
TI  - The use of the Ages and Stages questionnaire 3 (ASQ-3)..

PMID- 25612409
TI  - Screen time. How much is healthy for children?

PMID- 25612410
TI  - Public health priorities.

PMID- 25612411
TI  - Educational attainment of children and young people in the looked--after care
      system.
AB  - Over the last five years there has been a significant increase in the number of
      children in care. Despite service provision, the outcomes for these children
      differ significantly from their counterparts, particularly in relation to
      educational attainment. While 68% of children in care have special needs, this
      does not explain the difference in attainment for 32% of children in care.
      Research indicates that stereotyping, lower expectations and the experience of
      care are significant factors. Although positive work is being done, the
      differences in outcomes for children in care suggest further emphasis is needed.
      Experiences in early life impact on outcomes across the lifespan and it is here
      where as school nurses and health visitors, we can make a positive contribution
      for children in care.

PMID- 25612412
TI  - Implementing the Ages and Stages questionnaire in health visiting practice.
AB  - NHS South of Tyne and Wear introduced the Ages and Stages developmental screening
      tool as part of the health visiting core offer in June 2012. The tool comprises
      two sets of questionnaires, which cover the development of communication, gross
      and fine motor skills, problem-solving ability and personal-social skills (ASQ
      3], self- regulation, compliance, communication, adaptive functioning, autonomy,
      affect and interactions (ASQ-SE). ASQ was chosen over other screening tools for
      its reliability and validity. The introduction of the ASQ was to assist health
      visitors in the early detection of developmental problems and to support early
      interventions. By involving parents more, it was envisaged that they would be
      afforded a specific opportunity to think about how their child is developing, and
      should any developmental concerns become apparent, they would be more willing to
      accept referrals for early intervention. Initial feedback from parents and
      paediatricians has been positive. Most parents using the questionnaires felt that
      they were easy to complete and many found that they gained insight into their
      child's abilities. Further work should be undertaken to achieve a more
      representative sample of the target population.

PMID- 25612413
TI  - Parenting difficulties and postnatal depression: implications for primary
      healthcare assessment and intervention.
AB  - Postnatal depression [PND] is associated with impairments in the mother-child
      relationship, and these impairments are themselves associated with adverse child
      outcomes. Thus, compared to the children of non-depressed mothers, children of
      mothers with PND are more likely to be insecurely attached, and to have
      externalising behaviour problems and poor cognitive development. Each of these
      three child outcomes is predicted by a particular pattern of difficulty in
      parenting: insecure attachment is related to maternal insensitivity, particularly
      in relation to infant distress and emotional vulnerability; externalising
      problems are particularly common in the context of hostile parenting; and poor
      cognitive development is related to parental difficulties in noticing infant
      signs of interest and supporting their engagement with the environment. This
      article sets out procedures for how parenting could be assessed in ways that are
      sensitive to the domain-specific associations between parenting and child
      outcome, while remaining sensitive to the child's developmental stage. This set
      of assessments requires field testing.

PMID- 25612414
TI  - Preparation for birth and beyond: training the trainers.

PMID- 25612415
TI  - Celebrating success CPHVA Health Visitor of the Year.

PMID- 25612416
TI  - Healthy Internet use in young people.

PMID- 25612417
TI  - [Key problems in development of molecular identification in traditional Chinese
      medicine].
AB  - Molecular identification of Chinese traditional medicine has come from laboratory
      research into application, but there are some misunderstandings and problems
      emerging after rapid development. In this paper, we discuss the usage principle,
      hot field and technology innovation in molecular identification of Chinese
      traditional medicine. And molecular identification of traditional Chinese
      medicine has scientific and objective basis, follows the certain systematic
      research background, and adopts practical principles to establish case by case
      multi-class identification system. In order to achieve rapid, on-site, high
      throughput, low cost of traditional Chinese medicine identification purpose,
      molecular identification technology is further developing for meet the actual
      needs and the laboratory results further transformation in the service of
      traditional Chinese medicine industry.

PMID- 25612418
TI  - [Rapid PCR authentication Lonicera japanica].
AB  - To simply and rapid authenticate Lonicera japanica. Rapid allele-specific PCR
      primer was designed base on trnL-trnF 625 G/T Single nucleotide polymorphism and
      the PCR reaction systems including annealing temperature was optimized; optimized
      results were performed to authenticate L. japanica and its 9 adulterants. When
      100 x SYBR Green I was added in the PCR product of 87 degrees C initial denatured
      1 min; 87 degrees C denatured 5 s, 68 degrees C annealing 5 s, 30 cycle; L.
      japanica visualize strong green fluorescence under 365 nm UV lamp whereas
      adulterants without. The results indicate rapid allele-specific PCR could
      authenticate L. japanica and its adulterants rapidly and simply.

PMID- 25612419
TI  - [Application of rapid PCR to authenticate medicinal snakes].
AB  - To obtained an accurate, rapid and efficient method for authenticate medicinal
      snakes listed in Chinese Pharmacopoeia (Zaocysd humnades, Bungarus multicinctus,
      Agkistrodon acutus), a rapid PCR method for authenticate snakes and its
      adulterants was established based on the classic molecular authentication
      methods. DNA was extracted by alkaline lysis and the specific primers were
      amplified by two-steps PCR amplification method. The denatured and annealing
      temperature and cycle numbers were optimized. When 100 x SYBR Green I was added
      in the PCR product, strong green fluorescence was visualized under 365 nm UV
      whereas adulterants without. The whole process can complete in 30-45 minutes. The
      established method provides the technical support for authentication of the
      snakes on field.

PMID- 25612420
TI  - [Rapid extraction of DNA from Chinese medicinal products by alkaline lysis].
AB  - The study is aimed to explore a rapid method to extract DNA from fried Chinese
      medicinal products. The alkaline lysis buffer was made of sodium hydroxide, 1%
      PVP and 1% TritonX-100 and Tris-HCl solution was neutralized, through heat
      cracking and neutralization two step to extract DNA from processed and prepared
      products of traditional Chinese medicine. Then universal primes were used to
      amplify PCR products for fired Chinese medicinal materials. The results indicated
      the optimized alkaline lysis method for extracting DNA is quick and easy.
      Extracting of the different processed Sophora japonica of DNA concentration was
      (420.61 +/- 123.91) g x L(-1). Using 5% Chelex-100 resin purification can improve
      the DNA concentration. Our results showed that the optimized alkaline lysis
      method is suitable for Chinese medicinal materials for quickly DNA extraction.

PMID- 25612421
TI  - [Study on identification of cistanche hebra and its adulterants by PCR
      amplification of specific alleles based on ITS sequences].
AB  - To explore the new method of discriminating Cistanche deserticola, Cynomorium
      songaricum and Orobanche pycnostachya by using PCR amplification of specific
      alleles. 30 samples of the different C. deserticola, 21 samples of C. songaricum
      and O. pycnostachya were collected. The total DNA of the samples were extracted,
      the ITS sequences from C. deserticola, C. songaricum and O. pycnostachya were
      amplified by PCR and sequenced unidirectionally. These sequences were aligned by
      using ClustulW. Specific primer was designed according to the ITS sequences of
      specific alleles, and PCR reaction system was optimized. Additionally, compare
      with the identification of specific PCR method and DNA sequence analysis method.
      The result showed that the 331 bp identification band for C. deserticola and the
      adulterants not amplified bands by a single PCR reaction, which showed good
      identification ability to the three species. PCR amplification of specific
      alleles can be used to identify C. deserticola, C. songaricum and O. pycnostachya
      successfully.

PMID- 25612422
TI  - [Rapid molecular identification of pseudostellariae radix].
AB  - To establish a convenient and rapid method for identification of Pseudostellariae
      Radix by molecular identification, the rDNA-ITS sequences of Pseudostella
      riaheterophylla and its adulterants had been aligned to find out specific
      fragment. The specific primers against the fragment were designed and the PCR
      amplification conditions were optimized. The fluorescence reaction of the PCR
      products colored by 100 x SYBR Green I was observed under UV. The concentration
      of reaction buffer included 5.5 MUL DNA Taq polymerase premix, 10 pmol Tzs-2F and
      10 pmol Tzs-2R, 20-80 ng template DNA, and plus double sterile distilled water to
      25 MUL. The PCR thermal profile was as follows: predenaturation at 95 degrees C
      for 1 min, followed by 30 cycles of denaturation at 95 degrees C for 5 seconds,
      primer annealing and extension at 56 degrees C for 15 seconds, then it was
      extension at 72 degrees C for 30 seconds. The fluorescence reaction of
      Pseudostellariae Radix showed green fluorescence, while adulterants had not.
      Extraction, amplification DNA and all steps of molecular identification could be
      completed successfully in 40 minutes. The approach could amplify DNA template of
      Pseudostellariae Radix specificity, and its product with 1 MUL 100 x SYBR Green I
      could engender green fluorescence under UV. The method was simple and accurate,
      so it could be used for identification of Chinese traditional medicine.

PMID- 25612423
TI  - [Study on fluorescence sequencing typing technology identification of raw
      materials in liuwei dihuang pill].
AB  - In this paper, Liuwei Dihuang pill was used to study the identification of
      Chinese patent medicine by fluorescence sequencing typing technology. The DNA of
      Paeonia suffruticosa was used as template to amplify by five pair of FAM
      fluorescence labeling primers. Then, the amplified products were sequenced. The
      sequencing results were analyzed by GeneMarker V1.80 to screen the best
      fluorescence labeling primers. As a result, psbA-trnH fluorescence labeling
      primer was used to identify the raw materials of Liuwei Dihuang pill. The results
      showed that three kinds of raw plant medicinal materials in Liuwei Dihuang pill
      were able to be correctly identified by psbA-trnH fluorescence labeling primer.
      The fluorescence sequencing typing technology can stably and accurately
      distinguish raw medicinal materials in Chinese patent medicine.

PMID- 25612424
TI  - [Research on chemical reactions during ginseng processing].
AB  - As a kind of commonly used traditional Chinese medicine, ginseng has a high
      reputation at home and abroad. The research of ginseng has been expanded to
      medicine, pharmacy, biology, food science and other fields, with great
      achievements in recent years. Ginseng contains ginsenosides, volatile oil,
      carbohydrates, amino acids, polypeptides, inorganic elements and othser chemical
      constituents. Each component has extensive physiological activity, and is the
      base of ginseng's effect. After processing, the complicated changes are taken
      place in the constituents of ginseng, and some new substances produced. This
      paper aims to review the studies on chemical constituents and their mechanisms
      during ginseng processing, and the ideas, methods and the direction of the
      development of traditional Chinese medicine processing in the future.

PMID- 25612425
TI  - [Regulative mechanisms of oxidative stress in kidney in diabetic nephropathy and
      interventional effects of Chinese herbal medicine].
AB  - In the development of diabetic nephropathy (DN), reactive oxygen specie (ROS)
      over much in vivo leads to oxidative stress(OS)-related renal injuries, which are
      characterized by the structural and functional changes in glomerular and renal
      tubular cells in morphology. The regulative approaches of OS involve the several
      signaling pathways, in which, both p38 mitogen-activated protein kinase (MAPK)
      signaling pathway and adenosine monophosphate-activated protein kinase (AMPK)
      signaling pathway play the important roles as the target of anti-oxidants. The
      interventional actions of Chinese herbal compound prescriptions and the extracts
      of single Chinese herbal medicine (CHM) on OS in the kidney in DN include
      regulating the balance between ROS and antioxidants, reducing the production of
      AGEs, inhibiting the expression of growth factors and intervening the activity of
      signaling pathways.

PMID- 25612426
TI  - [New advance in studies on antimicrobal activity of Scutellaria baicalensis and
      its effective ingredients].
AB  - In recent years, with the constant increase in the population with hypoimmunity,
      bacterial and fungal infections have been increasing. Due to the drug resistance,
      clinically optional anti-bacterial and antifungal medicines become increasingly
      limited. Scutellaria baicalensis, a species of perennial herbaceous plant of
      scutellaria genus of lamiaceae family, and its effective components have multiple
      pharmacological effects such as anti-inflammation, anti-oxidation, anti-tumor,
      anti-microbial. Especially, its remarkable antibacterial and antifungal
      activities are of great significance to treat the increasing number of cases with
      drug-fast bacterial and antifungal infections. In this paper, the authors
      summarized the advance in studies on antibacterial and antifungal effects and
      mechanisms in recent years on the basis of the domestic and foreign studies on S.
      baicalensis and its effective ingredients.

PMID- 25612427
TI  - [Breviscapine listed on progress of new varieties and dosage form research].
AB  - Breviscapine, a flavone glucuronide, is a cardiovascular medicine extracted from
      a Chinese herb Erigeron breviscapinus. Modern pharmacological research shows
      breviscapine has a therapeutic effect on cardiovascular diseases such as cerebral
      thrombus,cerebral ischemia hemiparesis and platelet aggregation et al. However,
      its poor water solubility and low bioavailability in vivo severely restrict the
      clinical application. In this article, we reviewed the marketing preparations of
      breviscapine and its research progress on the new dosage forms.

PMID- 25612428
TI  - [Research on genetic stability to American ginseng introduced into China for 30
      years].
AB  - To study the genetic stability of Panax quinquefolium after introduced into China
      for 30 years, the samples of P. quinquefolium from 14 regions of China were
      studied. RAPD molecular marker technology was applied in this research, and
      POPGEN32 data analysis and NTSYS2. 10 cluster diagram were used to analyze the
      data. The results showed that there are abundant genetic diversity in the ginseng
      samples. There were 81 polymorphic bands based on the 13 random primers. The
      polymorphism was 83.51%, the effective number of alleles (N(e)) was 1.456 7;
      Nei's gene diversity index (H) was 0.274 8; Shannon's diversity index (H(o)) was
      0.419 4. The clustering analyses indicated that P. quinquefolium and P. ginseng
      were classified into two obvious groups, especially, it was also found that the
      P. quinquefolium could be divided into two obvious groups based on whether the P.
      ginseng was cultivated in the same region or not, but it was thought that there
      was not genetically a qualitative difference. Thus it suggests that a good
      breeding field should be established in Jilin Province of China for the germplasm
      purification.

PMID- 25612429
TI  - [Primary study of arginine as feed attractants on Whitmania pigra].
AB  - The effects of the feed attractants on Whitmania pigra were studied. The average
      weight of Wh. pigra were 5.0 g. Arginine was selected as feed attractants,
      xanthan gum was selected as feed substrate. The times of Wh. pigra going into the
      inducing room were recorded. The water temperature was 22-25 degrees C during the
      whole experiment. Arginine that had better inducing effect was chosen to carry on
      in the gradient experiment. The results showed that the best inducing effect was
      found when the added amount of arginine was 0.3%, which was close to the arginine
      content of the natural body fluid of Wh. Pigra and Bellamya purificata, 2.97 mg x
      g(-1).

PMID- 25612430
TI  - [Grain filling dynamics and germination characteristics of Bupleurum chinense
      seeds].
AB  - Bupleurum chinense used in the study were cultivated in the experimental fields
      of Gansu agricultural University for three years. The seeds of B. chinense were
      collected every 3 days 10 d after the blossom. The result showed that the 1 000
      grain fresh weight reached the maximum 43 d after the blossom and then decreased
      rapidly, at the mature period the fresh weight of seeds were falling to the same
      level of the dry weight. The dynamic change of the grain dry matter accumulation
      showed as an S-shape curve, the rapid increase stage was 25-34 d following the
      flower, and the grain filling was ended 46 d after blossom. Grain filling rate
      was under the law "fast-slow-fast-slow". And there were two peaks of grain
      filling rate appeared, after reached the second peak 28 d after the flower the
      filling rate decreased rapidly and stayed steadily 43 d after flowering. The
      dehydration rate was also measured at its maximum 43 d following flower. The
      indexes of seeds all reached the top 52 days following the blossom, when the
      germination rate reached the peak (34.33%) and water content of seeds was near
      10%. The rate of germination and the 1 000-graid weight of seed showed
      significant positive correlation, while the water content of seeds was found
      significant negatively correlation with germination percentage. So the best time
      for harvest should be 52 d after flowering (9 month), the seeds collected at that
      time showed both high quality and germination rate.

PMID- 25612431
TI  - [Morphology study on traditional Chinese medicine of animal skeleton of osteon
      myospalacem baileyi].
AB  - Sailonggu, a traditional Chinese medicine is whole skeleton of Myospalax baileyi,
      which is a kind of animal of rodent from Qinghai-Tibet Plateau of China. Osteon
      Myospalacem Baileyiis the first category medicinal materials of China Food and
      Drug Administration. For better quality control, a method of the morphological
      identification of Osteon Myospalacem Baileyi was established by means of studying
      characteristics of the animal skeleton, it's microscopic characteristics of
      powder, and literatures comparison. The characteristics of Osteon Myospalacem
      Baileyi were observed and recorded in detail and marked by number, which could be
      used for identifying crude drug of Osteon Myospalacem Baileyi efficiently.

PMID- 25612432
TI  - [Study on key physical properties of granulated products of Andrographis mixed
      powder by high-speed mixing wet method].
AB  - The impact of key physical properties on granulated products by the high-speed
      mixing wet method was studied. Andrographis extracts were utilized as the model
      drug. Four processing methods were adopted to prepare mixed powder of
      microcrystalline cellulose (MCC) and starch with the mass ratio 1:0.5, 1:1 and
      1:2 by the high-speed mixing wet method. The properties of the prepared granules
      were evaluated with such indexes as granule yield, the ratio of lumps and fine
      powder, granule-AOR and granule-HR. The impact of key physical properties on
      granulated products was analyzed through stepwise regression analysis. The
      results showed that angle of repose, moisture content, pore volume, density and
      contact angle with water were key physical properties of the powder. The key
      physical properties of Chinese medical extracts powder are the important factor
      impacting granulated products made by the high-speed mixing wet method. In this
      study, the impact of key physical properties on granulated products of Chinese
      medical extracts was analyzed from the physical angle.

PMID- 25612433
TI  - [Development of biphasic drug-loading lipid emulsion of Salvia miltiorrhiza and
      its quality evaluation].
AB  - The feasibility of simultaneously loading both liposoluble and water-soluble
      components of Salvia miltiorrhiza in emulsion was discussed, in order to provide
      new ideas in comprehensive application of effective components in S. miltiorrhiza
      in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic
      acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers,
      and glycerin as isoosmotic regulator, the central composite design-response
      surface method was employed to optimize the prescription. The coarse emulsion was
      prepared with the high-speed shearing method and then homogenized in the high
      pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared
      to investigate its pharmaceutical properties and stability. The prepared emulsion
      is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3
      mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic
      acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability
      among long-term retention samples. According to the results, the prepared
      emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic
      acid B simultaneously, which lays a pharmaceutical foundation for giving full
      play to the efficacy of S. miltiorrhiza.

PMID- 25612434
TI  - [Research on quality parameters of scutellariae radix (formula particles) using
      on-line NIR in pilot with different extraction process].
AB  - The on-line monitor for the changes in the content of baicalin in Scutellariae
      Radix formula particles during the extraction process was conducted by using near
      infrared spectroscopy (NIR). High performance liquid chromatography (HPLC) was
      used as a reference method. Kennard-Stone (KS) was used to divide sample sets, so
      as to compare different pretreatment methods. The synergy interval partial least
      squares (SiPLS) was used to screen out modeling wave band to establish partial
      least-squares models. The relative error method was applied to predict forecast
      set samples of Scutellariae Radix in three extraction phases. The results showed
      that the model established by Savitzky-Golay smoothing with 11 points (SG11
      points) was the best, with the root mean square with cross validation (RMSECV),
      root mean square error of correction (RMSEC) and root mean square error of
      prediction (RMSEP) of baicalin of 0.092 7, 0.134 4 and 0.114 8, respectively, the
      determination coefficient R2 of greater than 0.99, and the relative error of
      baicalin content of less than 5%. This indicates that the on-line near infrared
      reflectance spectroscopy could be applied in on-line monitor and quality control
      of the extraction process of Scutellariae Radix formula particles.

PMID- 25612435
TI  - [Discussing of influence mechanism of Chinese herbal monomer on physical
      stability of cream].
AB  - This study left flavonoids and alkaloids Chinese herbal monomer with common
      parent nucleus as cream base carriages drug respectively, cream base were
      prepared with stable span 60-tween 80 emulsification system. The near-infrared
      stability analysis technology was performed to quantitatively characterize the
      physical stability of cream. Base on the theory of gel network structure, theory
      of emulsification, theory of solubility parameter and theory of double layer, the
      influence mechanism of Chinese herbal monomer on physical stability of cream was
      discussed. The results showed that tetrahydropalmatine, matrine and naringenin
      had similar solubility parameter value with cream base material, creams prepared
      with those Chinese herbal monomer have higher Zeta potential value and stronger
      physical stability, and that those creams had similar microstructure information
      with cream base. However, a larger solubility parameter difference exists between
      baicalin, baicalein, berberine, palmatine and cream base material. Creams
      prepared with those Chinese herbal monomers had lower Zeta potential value and
      poorer physical stability, and that those creams had great different
      microstructure information with cream base.

PMID- 25612436
TI  - [Quality evaluation of bletillae rhizoma based on hemostatic biopotency].
AB  - This dissertation is to determine the biopotency of hemostat which processed in
      different places by establishing a bioassay method of Bletillae Rhizoma based on
      the thrombin time. Contrast test is the main methodology. Specifically, the
      reference substance of Bletillae Rhizoma is determined by comparing with the
      control substance of vitamin K1 using thrombin time, which is calibrated the
      Bletillae Rhizoma. The hemostatic biopotency is calculated by using the method of
      "parallel line assay method based on quantitative responses" (3.3) from different
      processed products. It indicates that there is a strong linear correlation
      between Bletillae Rhizoma and control drugs (Y = 66.332-23.913X, R2 = 0.995 3).
      The hemostatic biopotency of Bletillae Rhizoma from different processed products
      ranged between 821.93-1 187.53 U x g(-1) shown in the paper, and all of them can
      meet the requirements of the test. The methodology has an appropriate instrument
      precision (RSD 3.8%), intermediate precision (RSD 4.6%), repeatability (RSD 3.2%)
      and stability (RSD 3.7%). Therefore, it can be turned out that the methodology
      which established in the dissertation is good at determinating the hemostatic
      biopotency of Bletillae Rhizoma and it is reliable, simple and repeatable.

PMID- 25612437
TI  - [Study on HPLC fingerprint of jinzhen oral solution].
AB  - The HPLC fingerprint determination method of Jinzhen oral solution was
      established to provide a new method for quality control of Jinzhen oral solution.
      RP-HPLC was used for phenomenex Luna C18 (4.6 mm x 250 mm, 5 MUm) chromatographic
      column, with 0.1% H3 PO4 water solution and acetonitrile as the mobile phase for
      gradient elution. The detection wavelength was 280 nm. HPLC fingerprint of
      Jinzhen oral solution was established to identify 17 common peaks in Jinzhen oral
      solution. The similarity of fingerprints of 10 batches of finished products was
      more than 0. 90. The established HPLC fingerprint has a better precision,
      reproducibility and stability, and can be applied in quality control of Jinzhen
      oral solution.

PMID- 25612438
TI  - [Phenolic compounds from Rhododendron phaeochrysum var. agglutinatum].
AB  - Eight phenolic compounds were isolated from Rhododendron phaeochrysum var.
      agglutinatum and their sructures were identified as phaeochrysin (1), (2R)-4
      (3',4'-dihydroxyphenyl) -2-butanol (2), (-) -rhododendrol (3), rhododendrin (4),
      (+) -isolariciresinol (5), (-) -lyoniresinol (6), lyoniresinol-9'-O-beta-D
      xylopyranoside (7), and dihydrodehydrodiconiferyl-3a-O-alpha-L-rhamnopyranoside
      (8). Compound 1 is new, and compounds 2, 5-8 were isolated from this plant for
      the first time.

PMID- 25612439
TI  - [Study on chemical constituents from cultivated Gynura nepalensis].
AB  - Taking application of some isolation and purification technologies, such as
      solvent extraction, preliminary solvent isolation, column chromatographies over
      silica gel and Sephadex LH-20 gel and preparative HPLC, 10 compounds were
      obtained from Gynura nepalensis cultivated in the suburban area of Beijing. Their
      structures were identified by spectroscopic methods and comparison with
      literature as (3R) -3-hydroxy-beta-ionone (1), (3S,5R, 6S, 7E) -5, 6-epoxy-3
      hydroxy-7-megastigmen-9-one (2), (+) -boscialin (3), 3, 6-trans-3-hydroxy-alpha
      ionone (4), 3, 6-cis-3-hydroxy-alpha-ionone (5), 3, 4-cis-3, 4-dihydroxy-beta
      ionone (6), ethyl caffeate (7), loliolide (8), 1H-indole-3-carbaldehyde (9), and
      3-(hydroxyacetyl)indole (10), respectively. All compounds were isolated from the
      title plant for the first time, and with compounds 1, 2, 4-7, 9 and 10 being
      isolated from Gynura species for the first time. Structurally, the above
      compounds 1-6 belong to C13 nor-sesquiterpenoids, sharing the same carbon
      skeleton of megastigmane. According to this study, they are one of major kinds of
      chemical constituents of Gynura nepalensis and have important reference value for
      the investigation on phytotaxonomy of this species.

PMID- 25612440
TI  - [Study on steroidal saponins from Dioscorea zingiberensis and their platelet
      aggregation activities].
AB  - Using the absorbent resin, silica gel and ODS column chromatography as well as
      semi-preparative HPLC, ten compounds were isolated from 70% ethanol extract of
      tubers of Dioscorea zingiberensis C. H. Wright, and their structures were
      elucidated as trigoneoside XIIIa (1), parvifloside (2), trigoneoside IVa (3),
      deltoside (4), protobioside (5), lilioglycoside k (6), zingiberensis newsaponin I
      (7), deltonin (8), prosapogenin A of dioscin (9), and trillin (10) on the basis
      of NMR and MS spectral data analysis. Among these compounds, 1, 3, 5 and 6 were
      isolated from this plant for the first time. In the screening test on platelet
      aggregation, compounds 7 and 8 exhibited induction effect on platelet
      aggregation, while compound 9 exhibited significant inhibitory effect on platelet
      aggregation in vitro.

PMID- 25612441
TI  - [Homoisoflavanones and stilbenes from fresh bulb of Scilla scilloides].
AB  - Mian-Zao-Er was collected from the bulbs of Scilla scilloides (Lindl. ) Druce,
      belonging to the Hyacinthaceae family. 17 compounds were obtained using various
      column chromatographies on macroporus resin (HPD100), silica gel, Sephadex LH-20
      and ODS, as well as semi-preparative HPLC. Their structures were elucidated on
      the basis of physicochemical properties and spectral data as 2-hydroxy-7
      methoxyscillascillin (1), scillascillin (2), 5,7-dihydroxy-3',4'-dimethoxyspiro
      2H-1-benzopyran-7'-bicyclo[4.2.0 ] octa [1,3,5 ] -trien } -4-one (3), socialinone
      (4), 4-methylresveratrol (5), (E)-resveratrol (6), scillavoneA (7), 3,9-di-
      hydroeucomnalin (8), 3-(3-hydroxy-4-methoxybenzyl) -5,7-dihydroxychroman-4-one
      (9), (3R)-5,7,3'-trihydroxy-4'-methoxyspiro (2H-1-benzopyran-7'-bicyclo[4, 2, 0]
      octa [1, 3, 5]-trien} -4-one (10), scillabene A (11), 2-hydroxyscillascillin
      (12), 3-(4-hydroxybenzyl) -5,7-dihydroxychroman-4-one (13), 3-( 4
      hydroxybenzylidene) -5, 7-dihydroxychroman-4-one (14), 3-( 4-hydroxybenzyl) -5
      hydroxy-7,8-dimethoxychroman-4-one (15), 3-(4-hydroxybenzyl) -5-hydroxy-6, 7
      dimethoxychroman-4-one (16), and 3-(4-hydroxybenzyl)-5,8-hydroxy-7-methoxychroman
      4-one (17). Among them, compounds 3, 4, 6, 9, 13 and 15-17 were isolated from
      this plant for the first time.

PMID- 25612442
TI  - [Flavonoids from root of Machilus wangchiana].
AB  - Twelve flavonoids were isolated from an ethanol extract of Machilus wangchiana by
      a combination of various chromatographic techniques including column
      chromatography over silica gel and Sephadex LH-20 and reversed-phase flash
      chromatography and HPLC. Their structures were identified by spectroscopic data
      analysis (IR, MS, and NMR) as (+)-catechin (1), (-)-epicatechin (2), 3'-O-methyl
      (+)-catechin (3), 3'-O-methyl-(-)-epicatechin (4), 3, 5, 7, 2', 5'-pentahydroxy
      flavan (5), (-)-naringenin (6), (-)-eriodictyol (7), (-)-liquiritigenin (8),
      (2R,3R)-(+)-dihydrokaempferol (9), (2R,3S)-(-)-dihydro- kaempferol (10), (2R, 3R)
      (+)-taxifolin (11), and quercetin (12). Compounds 1-10 are isolated from the
      genus Machilus for the first time.

PMID- 25612443
TI  - [Simultaneous determination of gastrodin and eight nucleosides and nucleobases in
      Tibet cultured gastrodia elata by HPLC method].
AB  - This study aims to establish an HPLC method for simultaneous determination of
      gastrodin and eight nucleosides and nucleobases components in Gastrodia elata.
      The separation was carried out on an Agilent Zorbax Bonus-RP (4.6 mm x 250 mm, 5
      MUm) column with a methanol-(0.04% acetic acid) water solution gradient elution
      program at a flow rate of 1.0 mL x min(-1). The column temperature was 36 degrees
      C, and the detection wavelength was 254 nm. The volume of injection was 20 MUL.
      The nine components including gastrodin, cytosine, uracil, cytosine, adenine,
      thymine, uridine, guanosine and adenosine were well separated. The calibration
      curve was well linear in the range of 2.04-262.00 mg x L(-1), 0.20-24.67 mg x L(
      1), 0.18-23.75 mg x L(-1), 0.20-25.83 mg x L(-1), 0.20-26.67 mg x L(-1), 0.16
      20.00 mg x L(-1), 0.22-27.71 mg x L(-1), 0.20-24.29 mg x L(-1), 0.24-30.58 mg x
      L(-1), respectively, and the correlation coefficient was between 0.998 9-0.999 9.
      The average recovery of gastrodin and eight nucleosides and nucleobases were
      96.4%-99.6%, RSD less than 2.7% (n = 6). The contents of gastrodin in all the
      seven Tibet cultured Gastrodia elata samples were over 2 mg x g(-1). Further, all
      samples contain higher contents of adenosine, guanosine, uridine and cytidine
      compared to low contents of cytosine, uracil, adenine and thymine. The
      established method is accurate, reproducible and suitable for the determination
      of gastrodin and eight nucleosides and nucleobases comppnents in Gastrodia elata.

PMID- 25612444
TI  - [Quality control of Angelica sinensis with standard reference extract].
AB  - To improve the quality standard of Angelica sinensis, solve the problem of
      lacking relevant reference substance, a new method-based on the standard
      reference extract (SRE) was applied to achieve the quality control of Angelica
      sinensis. SRE of Angelica sinensis was obtained by chromatographic separation
      technology. After calibration of three makers of the SRE, an UPLC analytical
      method was developed to determinate the contents of the makers. T-test was used
      for comparison of the determination results of two methods (reference substances
      and SRE as reference, respectively), and the results demonstrated that there is
      no significant difference between the two methods. The presented method is very
      convenient and practical, which can be used for the quality control of Angelica
      sinensis.

PMID- 25612445
TI  - [ILs-HPLC simultanesous determination of five alkaloids in phellodenddri
      chinensis cortex].
AB  - A RP-HPLC method was established for simultaneous determination of phellodendrine
      hydrochloride (PH1), magnoflorine hydrochloride (MH), jatrorrhizine hydrochloride
      (JH), palmatine hydrochloride (PH2) and berberine hydrochloride (BH) in
      Phellodendri Chinensis Cortex by using ionic liquids as mobile phase additives.
      The separation was performed on a Kromasil C18 (4.6 mm x 250 mm, 5 MUm) coupled
      with ultraviolet (UV) detection. The effect of extraction solvent, detection
      wavelength, length of alkyl chain on different imidazolium ionic liquids and
      concentration of ionic liquids on the separation and determination of alkaloids
      were investigated. Ionic liquid, [BMIm] BF4, can obviously improve the resolution
      and peak shape. This ILs-HPLC method is simple, rapid, and reliable, which can be
      used for determination of alkaloids in Phellodenddri Chinensis Cortex.

PMID- 25612446
TI  - [Effect of traditional Chinese medicines with different properties on
      thermoregulation and temperature-sensitive transient receptor potentialion
      channel protein of rats with yeast-induced fever].
AB  - OBJECTIVE: To compare the intervention effects of four traditional Chinese
      medicines (TCMs) with typical cold or hot property on body temperature and
      temperature-sensitive transient receptor potential ion channel proteins (TRPs) of
      rats with yeast-induced fever. METHOD: The pyrexia model was induced by injecting
      yeast suspension subcutaneously. Totally 108 male SD rats were randomly divided
      into the normal group, the model group, the Rhei Radix et Rhizoma treated group,
      the Coptidis Rhizoma treated group, the Euodiae Fructus treated group, and the
      Alpiniae Officinarum Rhizoma treated group, with 18 rats in each group. At the 4
      h, 8 h and 12 h after injection of yeast, the rats were sacrificed to collect
      their hypothalamus and dorsal root ganglion. The expressions of TRPV1 and TRPM8
      were detected by immunohistochemistry and Western blot method. RESULT: Compared
      with the normal group, after injection of yeast, the temperature of rats in the
      model group notably increased, and reached the peak at 8 h (P < 0.01). The TRPV1
      level in hypothalamus and dorsal root ganglia (DRG) of the model group
      significantly increased, whereas the TRPM8 level significantly reduced. Compared
      with the model group, the Rhei Radix et Rhizoma group and the Coptidis Rhizoma
      group showed significant decrease in the high body temperature of rats caused by
      yeast, down-regulation in the expression of TRPV1, and up-regulation in the
      expression of TRPM8 (P < 0.05 or P < 0.01). Euodiae Fructus and Alpiniae
      Officinarum Rhizoma had no significant effect on either temperature or TRPs of
      fever rats. CONCLUSION: Rhei Radix et Rhizoma and Coptidis Rhizoma, both are TCMs
      with cold property, can reduce the temperature of fever rats induced by yeast,
      which may be related to their effective regulation of TRPV1 and TRPM8 in
      hypothalamus and DRG, while Euodiae Fructus and Alpiniae Officinarum Rhizoma had
      no relevant effect.

PMID- 25612447
TI  - [Anti-arthritic and anti-oxidative effect of ethyl acetate fraction of Blumea
      balsamlfera residues in rat adjuvant-induced arthritis].
AB  - OBJECTIVE: To study the effect of ethyl acetate fraction of Blumea balsamifera
      (BBE) residue on treating rats of adjuvant arthritis (AA) and its mechanism.
      METHOD: The rats were immunized with the Freund's complete adjuvant (FCA). After
      modeling, 28 days' treatment with BBE was performed. During the experimental
      process, rat mass, toe girth, arthritic index (AI), proliferation of immune
      organs and pathological section were measured. After treatment, blood samples
      were collected through fossa orbitalis vein for detection of serum SOD, MDA, GSH,
      NO, OH*, ALP, AST, ALT, NAG and SA content using colorimetric method and IL-1, IL
      6, TNF-alpha content using ELISA method. RESULT: Administration with BBE (high
      dose) could significantly ameliorate joint swelling and arthritis index,
      effectively inhibit synovial hyperplasia, down-regulate the levels of MDA, NO,
      OH*, ALP, AST, ALT, NAG, SA, IL-1, IL-6, TNF-alpha and up-regulate the SOD and
      GSH levels in serum. CONCLUSION: The results suggested BBE possesses substantial
      anti-arthritis and antioxidant activities.

PMID- 25612448
TI  - [Effect of Panax notoginseng saponins on liver drug metablic enzyme activity,
      mRNA and protein expressions in rats].
AB  - To study the effect of Panax notoginseng saponins (PNS) on liver drug metabolic
      enzyme activity, mRNA and protein expressions in rats. Male Wistar rats were
      randomly divided into nine groups. After administration of the test drugs, their
      liver microsomes, liver total RNA and total protein were extracted to detect the
      regulating effect of PNS on liver drug metabolic enzyme activity-related subtype
      enzymatic activity, mRNA and protein expression by substrate probe, quantitative
      PCR and Western Blot technology. The result of this experiment was that PNS could
      significantly induce CYP1A2 and CYP2E1 enzyme activity, mRNA expression, CYP2E1
      protein expression level. PNS significantly induced CYP3A mRNA expression, but
      with no significant effect in CYP3A enzyme activity level. PNS had no significant
      effect CYP1A1 and CYP2B mRNA expressions and enzyme activity levels. PNS had
      selective regulations on different P450 subtypes, and the major subtypes were
      CYP1A2 and CYP2E1. In clinical practice, particularly in the combination with
      CYP1A2 and CYP2E1 metabolism-related drugs, full consideration shall be given to
      the possible drug interactions in order to avoid potential toxic and side
      effects. Meanwhile, whether the induction effect of CYP2E1 gets involved in
      ginsenoside's effect incavenging free radicals deserves further studies.

PMID- 25612449
TI  - [Effect of total glucosides of paeony on Wnt/beta-catenin signal transduction
      pathway expression in kidney of diabetic rats].
AB  - The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/beta
      catenin signal transduction pathway expression in kidney of diabetic rats, and
      discuss the protection of TGP in diabetic nephropathy and possible mechanism.
      Ninety male SD rats of 8 weeks age were randomly divided into normal control
      group (n = 10) and model group (n = 80). Rats of the normal control group were
      fed with regular diet, while rats of the model group were fed with high-fat high
      sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x
      kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models
      were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x
      d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(
      1)) control group. Rats of DM group and each treatment group were given high-fat
      high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein,
      serum creatinine and blood urea nitrogen were tested. The rats were then
      sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and beta
      catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and
      beta-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and
      beta-catenin protein expression was semi-quantified by Western blot. The Result
      show that Wnt-1 and beta-catenin expression increased in kidney of high-fat high
      sugar induced type 2 diabetic rats. Compared with diabetic group, the level of
      serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area
      and mean glomerular volume were decreased, renal histopathology were improved,
      expression of Wnt-1 and beta-catenin mRNA and protein was reduced in TGP group.
      Tripterygium wilfordii glycosides had the similar effect. In conclusion, these
      results showed that Wnt/beta-catenin abnormal activation in kidney of type 2
      diabetic rats, TGP can improve kidney damage in diabetic rats and delay the
      development of diabetic nephropathy by inhibit the Wnt/beta-catenin signaling
      pathway.

PMID- 25612450
TI  - [Effects of isoquercitrin from Craibiodendron yunnanense on osteogenic
      differentiation of MC3T3-E1 cells].
AB  - Natural products especially flavonoids are being explored for their therapeutic
      potentials in reducing bone loss and maintaining bone health. The present study
      is to investigate the effects of isoquercitrin from Craibiodendron yunnanense
      with different concentrations at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7)
      mol x L(-1) on proliferation, differentiation and mineralization of MC3T3-E1.
      Cell proliferation was assessed by CCK-8 kit at 1, 3, 5 and 7 days of culture.
      Alkaline phosphatase (ALP) activity were performed qualitatively and
      quantitatively on day 7, and alizarin red S staining was employed to access the
      mineralization of cells on day 21. The osteogenic markers ALP, collagen type I
      (COL 1A1), runt-related transcription factor 2 (Runx-2) and Osterix were detected
      to analysis early osteogenic differentiation of cells on day 3 by RT-PCR. The
      results showed that isoquercitrin had a dose-dependent effect on the
      proliferation, osteogenic differentiation, mineralization and gene expression of
      MC3T3-E1 in the range from 1 x 10(-7) to 1 x 10(-5) mol x L(-1). At
      concentrations above 1 x 10(-4) mol x L(-1) isoquercitrin showed cytotoxicity,
      while 1 x 10(-6) mol x L(-1) is the optimal concentration of isoquercitrin to
      improve the osteoblastic activity. All these results implied that isoquercitrin
      might be the major composition of traditional Chinese medicine C. yunnanense to
      treat bone fractures.

PMID- 25612451
TI  - [Effects of glycyrrhizin acid and licorice flavonoids on LPS-induced cytokines
      expression in macrophage].
AB  - Glycyrrhizin acid and licorice flavonoids are the component of Glycyrrhiza
      uralensis Fisch root that has been used for various medicinal purposes in
      traditional oriental medicine for thousands of years. Macrophages as a principal
      component of immune system play an important role in the initiation, modulation
      and final activation of immune response against pathogens. In the present study,
      glycyrrhizin acid and licorice flavonoids was investigated the anti-inflammatory
      effect on lipopolysaccharide (LPS)-induced macrophage cell line of RAW264.7. Well
      grown RAW264.7 cells were collected and randomly divided into the blank control
      group, the LPS(1 mg x L(-1)) group, the dexamethasone (5 mg x L(-1)) with LPS
      group, the glycyrrhizin acid (400, 80, 16 mg x L(-1)) with LPS group and the
      licorice flavonoids (200, 40, 8 mg x L(-1)) with LPS group. RAW264.7 cells were
      cultured in 24-well plates, pre-incubated for 4 h with different concentrations
      of dexamethasone, glycyrrhizin acid, or licorice flavonoids. Then cells were
      stimulated for 20 h with LPS. The supernatant of culture medium was collected
      from each well and determinated the concentrations of cytokines by means of
      BioPlex mouse cytokines assay. Compared with the control group, the LPS group
      could significantly induced relatively high levels of granulocyte colony
      stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor( GM
      CSF), macrophage inflammatory protein-1 alpha (MIP-1alpha), macrophage
      inflammatory protein-1 beta (MIP-1beta), regulated upon activation normal T cell
      expressed and secreted factor (RANTES), tumor necrosis factor alpha ( TNF-alpha),
      monocyte chemotactic protein 1 (MCP-1), chemokine (C-X-C motif) ligand 1 (KC),
      eotaxin, interleukin(IL)-1alpha, IL-1beta, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12
      (p40), IL-12 (p70), IL-13, and IL-17 secretion (P < 0.05). The glycyrrhizin acid
      significantly inhibited IL-1beta, IL-3, IL-5, IL-6, IL-10, IL-12 (p40), IL-12
      (p70), IL-13, Eotaxin and TNF-alpha secreted by LPS-stimulated RAW264.7 cells (P
      < 0.05). The expression levels of IL-6 and Eotaxin were observably decreased in
      the licorice flavonoids with LPS group (P < 0.05). The data presented here
      suggested that the glycyrrhizin acid and licorice flavonoids modulate various
      cytokines secreted by macrophages and were important anti-inflammatory
      constituent of Licorice.

PMID- 25612452
TI  - [Neuroprotective effect of curcumin to Abeta of double transgenic mice with
      Alzheimer's disease].
AB  - OBJECTIVE: To observe the changes in Abeta40, Abeta42 and ADDLs in brains of 3
      month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with
      curcumin, in order to discuss the neuroprotective effect of curcumin. METHOD:
      APPswe/PS1dE9dtg mice were randomly divided into the model group, the
      Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x
      d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage
      groups, with C57/BL6J mice of the same age and the same background in the normal
      control group. After 6 months, the immunohistochemical staining (IHC) and the
      Western blot method were used to observe the changes in positive cell of Abeta40,
      Abeta42 and ADDLs in hippocampal CA1 area, their distribution and protein
      expressions. RESULT: Both of the immunohistochemical staining and the Western
      blot method showed more positive cell of Abeta40, Abeta42 and ADDLs in
      hippocampal CA1 area and higher protein expressions in the model group than the
      normal group (P < 0.01). IHC showed a lower result in the Rosiglitazone group
      than the model group (P < 0.05), while Western blot showed a much lower result (P
      < 0.01). The number of Abeta40, Abeta42 and ADDLs positive cells and the protein
      expressions decreased in the curcumin high group, the medium group showed a
      significant decrease (P < 0.01), and the low dose group also showed reductions in
      the protein expressions of Abeta40 and Abeta42. CONCLUSION: The six-month
      intervention with curcumin can significantly reduce the expressions of
      hippocampal Abeta40, Abeta42 and ADDLs in brains of APPswe/PS1dE9 double
      transgenic mice. Whether curcumin can impact Abeta cascade reaction by down
      regulating expressions of Abeta40, Abeta42 and ADDLs and show the neuroprotective
      effect needs further studies.

PMID- 25612453
TI  - [Simultaneous determination of four anthraquinones in rat plasma by HPLC-FLD
      method and its pharmacokinetic study].
AB  - This paper aims to develop a method for the determination of aloe-emodin, rhein,
      chrysophanol and physcion and study the pharmacokinetic properties of four
      anthraquinones in rat plasma after oral administration of gardenia and rhubarb
      decoction. The plasma concentrations at different time points of four
      anthraquinones were determined by HPLC-FLD method. Plasma samples were extracted
      with liquid-liquid extraction procedure. Plasma samples were separated on a C18
      column (4.6 mm x 150 mm, 5 MUm), using 0.2% acetic acid and methanol as mobile
      phase at a flow rate of 1.0 mL min(-1) with gradient elution. The excitation and
      emission wavelengths were set at 430, 525 nm, respectively. DAS 2.0 software was
      applied to calculate the pharmacokinetic parameters. The results showed four
      anthraquinones can be absorbed. The main parameters of aloe-emodin, rhein,
      chrysophanol and physcion were as follows: C(max) for aloe-emodin was (0.085 +/-
      0.058), (3.772 +/- 1.152), (0.464 +/- 0.267), (0.028 +/- 0.008) mg x L(-1)
      respectively; t(max) for rhein was (1.042 +/- 0.510), (0.805 +/- 0.307), (1.167
      +/- 0.283), (0.616 +/- 0.162) h respectively; t1/2 for chrysophanol was (3.557 +/
      1.250), (6.879 +/- 1.126), (5.196 +/- 2.032), (4.337 +/- 1.816) h; AUC(0-t) for
      physcion was (0.504 +/- 0.130), (9.558 +/- 1.106), (2.545 +/- 1.554), (0.052 +/-
      0.018) mg x h x L(-1). This paper developed a selective, accurate and sensitive
      HPLC-FLD method for the simultaneous determination of four anthraquiones in rat
      plasma.

PMID- 25612454
TI  - [Identification of metabolites of epiberberine in rat liver microsomes and its
      inhibiting effects on CYP2D6].
AB  - Epiberberine, one of the most important isoquinoline alkaloid in Coptidis
      Rhizoma, possesses extensive pharmacological activities. In this paper, the
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase
      I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor
      LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed
      to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone
      and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4,
      CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat
      liver microsomes. The result showed that epiberberine may have phase I and phase
      II metabolism in the rat liver and two metabolites in phase I and three
      metabolites in phase II are identified in the temperature incubation system of in
      vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with
      IC50 value of 35.22 MUmol L(-1), but had no obvious inhibiting effect on the
      activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that
      epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study
      aims to provide a reliable experimental basis for its further research and
      development of epiberberine.

PMID- 25612455
TI  - [Preliminary study on relationship of disease-syndrome-symptom of ovulatory
      disorder infertility based on factor analysis].
AB  - OBJECTIVE: In this study, the clinical data of 240 cases of data acquisition on
      ovulation in patients with anovulatory infertility. METHOD: Using the method of
      factor analysis, summed up the distribution situation of various syndromes and
      the relationship of disease-syndrome-symptom. RESULT: From the study we found
      that polycystic ocary syndrome > premature ovarian failure > corpus luteum
      insufficiency > luteinized unruptured follicle syndrome > hyperprolactinemia >
      anovulatory dysfunctional uterine bleeding. Using the factor analysis method, the
      syndromes of anovulatory infertility were divided into six types and the
      distribution proportion of them is: kidney Yang deficiency and blood stasis >
      kidney Yang deficiency > kidney Yin deficiency and blood stasis > kidney Yin
      deficiency and liver Qi stagnation syndrome > kidney Yang deficiency and phlegm
      dampness stagnation > kidney Yin deficiency. By means of statistics, the
      traditional Chinese medicine (TCM) symptoms as abdomen pain before menstrual
      onset, obfuscation colour, cold lower abdomen, insomnia, fatigue, eyes dark, face
      dark or ring lip dark, before and after menstruation breast swelling, chest
      tightness, irritable insomnia, depression and lower abdomen pain during
      menstruation etc contribute high degree in the process. CONCLUSION: Polycystic
      ovary syndrome and premature are the main causes of ovulatory disorder
      infertility and the disease incidence rate assumed the tendency which rose year
      by year. The treatment of the disease of kidney yang deficiency syndrome scales
      biggest the disease degree of contribution. Blood stasis is the important factor
      in the process of pathogenesis evolution. In the study of disease distribution,
      we found that symptom distribution trend roughly the same and the same symptom
      severity in different diseases with different, which provides experience for the
      theory-different diseases with the same therapeutic method. These conclusions
      provide guidance and reference evidences for clinic practice.

PMID- 25612456
TI  - [Overview of application and research of Echinops genus in Chinese medicine].
AB  - Asteraceae Echionopos (Echinops genus) is one of the world's plants commonly used
      in traditional Chinese medicine herbs. In this paper, a lot of literature on the
      basis of domestic and foreign, and modern research on the application of
      medicinal plants in different ethnic groups in our country Echionopos made a
      brief presentation and evaluation, and its in Chinese Han, Mongolian, Uygur,
      Kazak, Korean and other ethnic groups in the application of traditional medicine
      and related research conducted profiles. To further comprehensive and accurate
      use of the abundant plant resources and research, in order to find biologically
      active natural products, provide reference basis for the clinical application of
      new drugs developed and expanded drug source.

PMID- 25612457
TI  - [Regularity of drugs compatibility of anti-hepatoma traditional Chinese medicine
      ancient prescriptions and risk evaluation of anti-hepatoma new drug research and
      development].
AB  - Traditional Chinese ancient prescriptions have been used for treatment of liver
      cancer for a long history and the scientific and rational compatibility is a
      great wealth for modern research and development (R&D) of new drugs. The research
      and development of new drugs are often accompanied with a large investment, a
      long cycle and a high risk, especially for the anti-tumor drugs R&D which are
      facing more risks and lower successful rate. In this research, the regularity of
      compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions
      by computer program. The results can offer help to the R&D of anti-hepatoma new
      drugs and reduce the risk of drug screening. In addition, we surveyed 22
      companies in this field from six provinces such as Beijing, Shanghai, Tianjin and
      so on and obtained 240 risk assessment questionaires. Then we used qualitative
      analysis method to interpret the greatest impacts for the risks in the process of
      R&D, production and sales of anti-hepatoma new drugs. The study provides a basis
      for anti-liver cancer drugs R&D researchers, who can take effective measures to
      reduce the R&D risks and improve successful rate.

PMID- 25612458
TI  - [Understanding differences between Rheum palmatum and R. franzenbachii from
      perspective of chemistry, efficacy and toxicity].
AB  - Rheum franzenbachii (called Tudahuang in local) has some similarities with R.
      palmatum (rhubarb) collected by "China Pharmacopoeia" and is often used as a
      substitute of rhubarb. Can Tudahuang simply replace rhubarb in the application or
      whether is there difference between Tudahuang and rhubarb, and what is the
      difference it is important to verify the difference and understand its proper
      application in the field of clinical practice. In this paper, we discussed the
      differences of the two herbs from the views of chemistry, efficacy and toxicity
      based on the author's previous research work as well as literatures, by using the
      major role of the rhubarb "diarrhea" as the basic point. The analysis result
      showed that the role of diarrhea Tudahuang was much weaker than that of rhubarb.
      The reason lies in the difference between the contents of combined anthraquinones
      component. While acute toxicity in mice of Tudahuang is stronger than that of
      rhubarb. Thus, Tudahuang should not simply replace rhubarb in practice.

PMID- 25612459
TI  - Use of targeted SNP selection for an improved anchoring of the melon (Cucumis
      melo L.) scaffold genome assembly.
AB  - BACKGROUND: The genome of the melon (Cucumis melo L.) double-haploid line DHL92
      was recently sequenced, with 87.5 and 80.8% of the scaffold assembly anchored and
      oriented to the 12 linkage groups, respectively. However, insufficient marker
      coverage and a lack of recombination left several large, gene rich scaffolds
      unanchored, and some anchored scaffolds unoriented. To improve the anchoring and
      orientation of the melon genome assembly, we used resequencing data between the
      parental lines of DHL92 to develop a new set of SNP markers from unanchored
      scaffolds. RESULTS: A high-resolution genetic map composed of 580 SNPs was used
      to anchor 354.8 Mb of sequence, contained in 141 scaffolds (average size 2.5 Mb)
      and corresponding to 98.2% of the scaffold assembly, to the 12 melon chromosomes.
      Over 325.4 Mb (90%) of the assembly was oriented. The genetic map revealed
      regions of segregation distortion favoring SC alleles as well as recombination
      suppression regions coinciding with putative centromere, 45S, and 5S rDNA sites.
      New chromosome-scale pseudomolecules were created by incorporating to the
      previous v3.5 version an additional 38.3 Mb of anchored sequence representing
      1,837 predicted genes contained in 55 scaffolds. Using fluorescent in situ
      hybridization (FISH) with BACs that produced chromosome-specific signals, melon
      chromosomes that correspond to the twelve linkage groups were identified, and a
      standardized karyotype of melon inbred line T111 was developed. CONCLUSIONS: By
      utilizing resequencing data and targeted SNP selection combined with a large F2
      mapping population, we significantly improved the quantity of anchored and
      oriented melon scaffold genome assembly. Using genome information combined with
      FISH mapping provided the first cytogenetic map of an inodorus melon type. With
      these results it was possible to make inferences on melon chromosome structure by
      relating zones of recombination suppression to centromeres and 45S and 5S
      heterochromatic regions. This study represents the first steps towards the
      integration of the high-resolution genetic and cytogenetic maps with the genomic
      sequence in melon that will provide more information on genome organization and
      allow for the improvement of the melon genome draft sequence.

PMID- 25612460
TI  - Perforation of the neovagina in a male-to-female transsexual: a case report.
AB  - INTRODUCTION: There are several techniques for creation of a neovagina in male-to
      female reassignment surgery. Although vaginoplasty with the sigmoid colon is not
      a common procedure, it is becoming more common. Perforation of the recto-sigmoid
      neovagina after sex reassignment surgery is very rare. We hereby report a case of
      perforation of the neovagina that presented as acute peritonitis, with a massive
      abscess in the intra-abdominal cavity. CASE PRESENTATION: This case report
      describes a 33-year-old Asian woman presenting with mild persistent abdominal
      pain, nausea, and vomiting who had undergone male-to-female sex reassignment
      surgery four years prior. Physical examination revealed mild abdominal pain
      without rebound tenderness. An abdominal computed tomography scan showed a
      massive abscess that occupied a significant portion of the intra-abdominal
      cavity. Perforation of the neovagina was confirmed by exploratory laparotomy and
      surgical drainage with primary closure was performed without any complications.
      CONCLUSION: This is a rare case involving perforation of the neovagina that was
      successfully treated with surgical intervention. This case emphasizes the
      importance of taking a detailed medical history and to make physicians and
      patients aware that bowel vaginoplasty can result in a weak vagina.

PMID- 25612461
TI  - DEK1; missing piece in puzzle of plant development.
AB  - Patterning of land plant bodies is determined by positioning of cell walls. A
      crucial event in land plant evolution was the ability to utilize spatial
      information to direct cell wall deposition. Recent studies of DEK1 in
      Physcomitrella patens support a role for DEK1 in position dependent cell wall
      orientation. 

PMID- 25612462
TI  - Neurocognitive impairment on motor imagery associated with positive symptoms in
      patients with first-episode schizophrenia: evidence from event-related brain
      potentials.
AB  - Motor imagery provides direct insight into an anatomically interconnected system
      involved in the integration of sensory information with motor actions, a process
      that is associated with positive symptoms in schizophrenia (SCZ). However, very
      little is known about the electrophysiological processing of motor imagery in
      first episode SCZ. In the current study, we used a visual hand mental rotation
      (MR) paradigm to manipulate the processing of motor imagery while event-related
      brain potentials (ERPs) were recorded in 42 SCZ participants and 40 healthy
      controls (HC). The 400-600 ms window was measured and analyzed for peak latencies
      and amplitudes. Participants with SCZ had slower reaction time (RT) and made more
      errors than did HC participants. Moreover, SCZ participants had lower amplitudes
      in the 400-600 ms window and the typical MR function for amplitudes of MR was
      lacking. Interestingly, the scalp activity maps for MR in SCZ exhibited an
      absence of activation in the left parietal site as shown in HC. Furthermore,
      deficits of amplitude for MR were positively correlated with positive symptom
      scores in SCZ. These results provide novel evidence for relationships between the
      electrophysiological processing of motor imagery and positive symptoms in SCZ.
      They further suggest that the impaired information processing of motor imagery
      indexed by amplitudes and specific topographic characteristics of the EEG during
      MR tasks may be a potentially useful and early defining biomarker for SCZ.

PMID- 25612464
TI  - Clinical, biochemical and histological study of the effect of antimicrobial
      photodynamic therapy on oral mucositis induced by 5-fluorouracil in hamsters.
AB  - Oral mucositis (OM) is a debilitating side effect of chemotherapy, which can be
      relieved by phototherapy. Antimicrobial photodynamic therapy (aPDT) may be used
      for the treatment of OM, when infection is present. However, there are no studies
      showing that aPDT affects tissue repair process when used in the treatment of
      lesions caused by OM. This work aims to evaluate the effect of aPDT in healing OM
      induced by 5-Fluorouracil (5-FU). Two hundred forty-five hamsters were divided
      into two groups, control (C) and experimental, which were subdivided into 4
      subgroups (Ch, ChP, ChL, aPDT). C group received only the vehicle of chemotherapy
      and anesthesia, whereas all animals of the experimental groups received
      anesthesia and chemotherapy agent 5-FU to induce OM. Ch group received no OM
      treatment; ChP group received an application of methylene blue (MB) 0.01%; ChL
      received irradiation with low-power-laser (LPL-660 nm/120 J /cm(2)/40 mW/4.4 J
      per point); and aPDT received MB and LPL irradiation. OM Clinical severity were
      daily assessed by a blinded examiner. The animals were sacrificed after 5, 7 and
      10 days of experiment and their oral mucosa were removed for biochemical
      (enzymatic activity of SOD and catalase) and histological analyzes (light
      microscopy). After statistical analysis was performed, results showed that aPDT
      reduced the severity of OM on the tenth day of the experiment, when compared to
      the initial OM score (p < 0.05), as well as increased keratinization with
      organized collagen deposition in the lamina propria. In conclusion, aPDT can be
      safely used in animals with infected OM because it does not affect lesion
      repairing processes.

PMID- 25612465
TI  - Central venous pressure and renal function in very low birth weight infants
      during the early neonatal period.
AB  - OBJECTIVE: To observe central venous pressure (CVP) and to address the
      association with hemodynamic and renal parameters in very low birth weight
      infants (VLBWI) during the early neonatal period. METHODS: CVP levels were
      prospectively measured every 4 h in VLBWI with an umbilical venous catheter for
      at least the initial 5 d of life. The association of CVP with mean blood
      pressure, serum B-type natriuretic peptide, serum creatinine, fluid intake, and
      urine output were analyzed. RESULTS: In 25 infants, the mean daily CVP (mCVP)
      value of 3.5 +/- 2.2 mmHg did not change between day 1 and day 7 after birth.
      There were no significant correlations between mCVP and mean blood pressure,
      serum BNP, serum creatinine, fluid intake, and urine output over the total study
      period. However, the mCVP was significantly correlated with urine output and
      serum creatinine 96-144 h after birth. CONCLUSIONS: After the transitional
      period, mCVP values were associated with renal function parameters in VLBWI.

PMID- 25612466
TI  - A rare entity: idiopathic priapism in a newborn and review of the literature.
AB  - Priapism is a pathological condition of a penile erection that persists beyond or
      is unrelated to sexual stimulation. Priapism is an important medical condition,
      which requires evaluation and may require emergency management. This condition
      occurs very infrequently in paediatrics outside of the sickle-cell population and
      is exceedingly rare in newborns. The evaluation and management of neonatal
      priapism can be challenging for paediatricians, neonatologists and paediatric
      urologists alike given the lack of experience with this condition, its poorly
      understood pathophysiology and the absence of well-established guidelines. We
      present a case of idiopathic neonatal priapism because of its rarity and review
      of the literature. 

PMID- 25612467
TI  - Electric shock in pregnancy: a review.
AB  - OBJECTIVE: The effect of gestational age and other factors that could influence
      the outcome of an electric shock in pregnancy have not been defined yet.
      Objective of this study is to provide reliable data on medical issues linked to
      electric shock in pregnancy. METHODS: Authors consulted the most important
      scientific databases investigating reactions to electric shock in pregnancy,
      analyzing mechanism of electric shock, gestational age at the time of injury, the
      post-shock complications, interval from injury to delivery and fetal and maternal
      outcome. RESULTS: The spectrum of electrical injuries in pregnancy ranges from
      transient unpleasant sensation with no effect on the fetus to sudden maternal and
      fetal death. The clinical presentation of the fetal injury may manifest
      immediately or even postnataly. Reported outcomes include spontaneous abortion,
      placental abruption, cardiac arrhythmias, fetal burn and intrauterine fetal
      death. If the pregnancy is continued, decreased fetal movements and asphyxia,
      pathological fetal heart patterns, intrauterine fetal growth retardation, damage
      to the fetal central nervous system and oligoamnios can occur. CONCLUSIONS: More
      large prospective observational studies are necessary for a proper insight into
      the expected outcomes of the electric shock in pregnancy as well as for a final
      definition of monitoring procedures of such pregnancies.

PMID- 25612463
TI  - Therapeutic phlebotomy is safe in children with sickle cell anaemia and can be
      effective treatment for transfusional iron overload.
AB  - Serial phlebotomy was performed on sixty children with sickle cell anaemia,
      stroke and transfusional iron overload randomized to hydroxycarbamide in the
      Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy
      procedures with only 33 adverse events, all of which were grade 2. Among 23
      children completing 30 months of study treatment, the net iron balance was
      favourable (-8.7 mg Fe/kg) with significant decrease in ferritin, although liver
      iron concentration remained unchanged. Therapeutic phlebotomy was safe and well
      tolerated, with net iron removal in most children who completed 30 months of
      protocol-directed treatment.

PMID- 25612468
TI  - The role of inferior vena cava diameter in the differential diagnosis of dyspneic
      patients; best sonographic measurement method?
AB  - STUDY OBJECTIVE: We aimed to determine the role of inferior vena cava (IVC)
      diameter in making a differentiation between dyspnea of cardiac (acute heart
      failure [AHF]) and pulmonary origin. We also attempted to determine the best
      sonographic method for the measurement of IVC diameter. METHODS: This prospective
      observational study was conducted at the intensive care unit of the emergency
      department of a training and research hospital. This study enrolled patients with
      the main symptom of dyspnea who were categorized into 2 groups, cardiac dyspnea
      and pulmonary dyspnea groups, based on the final diagnosis. All patients
      underwent sonographic measurement of minimum and maximum diameters of IVC, and
      the caval index (CI) was calculated in both M-mode and B-mode. The sensitivity,
      specificity, and likelihood ratios (LR) of the IVC values for the differentiation
      of the 2 groups were calculated. RESULTS: This study included a total of 74
      patients with a mean age of 72.8 years. Thirty-two patients had dyspnea of
      cardiac origin, and 42 patients had dyspnea of pulmonary origin. The IVC diameter
      measured with B-mode during inspiration (B-mode i) was the most successful method
      for differentiation of the 2 groups. B-mode i values greater than 9 mm predicted
      dyspnea of cardiac origin with a sensitivity of 84.4% and a specificity of 92.9%
      (+LR: 11.8, LR: 0.16). CONCLUSION: Sonographic assessment of the IVC diameter may
      be used as a rapid, readily, nonexpensive, complication-free, and reproducible
      technique for the differentiation of cardiac and pulmonary causes of dyspnea. B
      mode i measurement may be more successful in the differentiation of dyspnea
      compared with other IVC diameters and calculations.

PMID- 25612469
TI  - Prolonged-release oxycodone/naloxone in opioid-naive patients - subgroup analysis
      of a prospective observational study.
AB  - OBJECTIVE: Prolonged-release oxycodone/naloxone (OXN PR) showed improved
      gastrointestinal tolerability and equivalent analgesic efficacy compared to
      oxycodone alone in patients with non-cancer pain or cancer pain. This is the
      first dataset to demonstrate its effectiveness and safety compared to other
      strong opioids in opioid-naive patients. METHODS: This is a subgroup analysis of
      a 4- to 6-week multicenter, observational study. A total of 162 opioid-naive
      patients with moderate-to-severe pain of varying etiologies received either OXN
      PR or other strong opioids (control group). Documented parameters include pain
      relief (numeric rating scale), bowel function (Bowel Function Index [BFI]), pain
      related functional impairment (Brief Pain Inventory Short Form), quality of life
      (QoL; EuroQol EQ-5D-3L) and a global therapy assessment. RESULTS: OXN group
      patients experienced a substantial clinically important reduction in mean pain
      intensity of 51.4%, compared to a 28.6% reduction in control patients. Although
      the BFI remained in the reference range in both groups, there was a difference
      between BFI changes during treatment in favor of OXN PR. The superior
      effectiveness of OXN PR was paralleled by greater improvements of pain
      interference and QoL and fewer adverse drug reactions compared to other strong
      opioids. CONCLUSION: The favorable outcomes under real-life conditions suggest
      that OXN PR provides a valuable option for treatment of moderate-to-severe pain
      without using weak opioids first.

PMID- 25612470
TI  - Fluorescent graphene oxide via polymer grafting: an efficient nanocarrier for
      both hydrophilic and hydrophobic drugs.
AB  - Functionalized graphene-based drug delivery vehicles have conquered a significant
      position because functionalization improves its biocompatibility and stability in
      cell medium, leaving sufficient graphitic basal plane for drug loading through pi
      pi stacking. In this study, poly(N-isopropylacrylamide) (PNIPAM) is covalently
      grafted from the surface of graphene oxide (GO) via a facile, eco-friendly and an
      easy procedure of free radical polymerization (FRP) using ammonium persulfate
      initiator. Various spectroscopic and microscopic studies confirm the successful
      grafting of PNIPAM from GO surface. PNIPAM-grafted GO (GPNM) exhibits enhanced
      thermal stability, improved dispersibility both in aqueous and cell medium, and
      better biocompatibility and cell viability compared to GO. Interestingly, GPNM
      displays an exciting fluorescence property in aqueous medium, which is a hike of
      intensity at 36  degrees C due to the lower critical solution temperature (LCST)
      of PNIPAM chains (32  degrees C). Moreover both hydrophilic (doxorubicin (DOX))
      and hydrophobic (indomethacin (IMC)) drugs loaded on the surface of GPNM hybrid
      exhibits its efficacy as an efficient carrier for both types of drugs. Cellular
      uptakes of free DOX and DOX-loaded GPNM (GPNM-DOX) are evidenced both from
      optical and fluorescence imaging of live cells, and the efficiency of drug is
      significantly improved in the loaded system. The release of DOX from GPNM-DOX was
      achieved at pH 4, relevant to the environment of cancer cells. The pH-triggered
      release of hydrophobic drug was also studied using UV-vis spectroscopy via
      alginate encapsulation, showing a great enhancement at pH = 7.4. The IMC is also
      found to be released by human serum albumin using dialysis technique. The GPNM
      nanomaterial shows the property of simultaneous loading of DOX and IMC as well as
      pH-triggered simultaneous release of both of the drugs. 

PMID- 25612472
TI  - Ethanol exposure induces a delay in the reacquisition of function during head
      regeneration in Schmidtea mediterranea.
AB  - Prenatal exposure to ethanol affects neurodevelopmental processes, leading to a
      variety of physical and cognitive impairments collectively termed Fetal Alcohol
      Spectrum Disorders (FASD). The molecular level ethanol-induced alterations that
      underlie FASD are poorly understood and are difficult to study in mammals.
      Ethanol exposure has been shown to affect regulation and differentiation of
      embryonic stem cells in vitro, suggesting that in vivo effects such as FASD could
      arise from similar alterations of stem cells. In this study, we hypothesize that
      ethanol exposure affects head regeneration and neuroregeneration in the Schmidtea
      mediterranea planarian. S. mediterranea freshwater flatworms have remarkable
      regenerative abilities arising from an abundant population of pluripotent adult
      somatic stem cells known as neoblasts. Here, we evaluated the mobility-normalized
      photophobic behavior of ethanol-exposed planaria as an indicator of cognitive
      function in intact and head-regenerating worms. Our studies show that exposure to
      1% ethanol induces a delay in the reacquisition of behavior during head
      regeneration that cannot be attributed to the effect of ethanol on intact worms.
      This suggests that the S. mediterranea planarian could provide insight into
      conserved neurodevelopmental processes that are affected by ethanol and that lead
      to FASD in humans. 

PMID- 25612473
TI  - Percutaneous mitral valve repair with MitraClip system in a patient with acute
      mitral regurgitation after myocardial infarction.

PMID- 25612475
TI  - Estimated GFR is biased by non-traditional cardiovascular risk factors.
AB  - BACKGROUND: Estimated glomerular filtration rate (eGFR) based on either cystatin
      C or creatinine performs similarly in estimating measured GFR, but associate
      differently with cardiovascular disease (CVD) and mortality. This could be due to
      confounding by non-GFR-related traits associated with cystatin C and creatinine
      levels. We investigated non-GFR-related associations between eGFR and two types
      of nontraditional risk factors for CVD and death: L-arginine/dimethylarginine
      metabolism and insulin resistance. METHODS: GFR was measured via iohexol
      clearance in a cross-sectional study of 1,624 middle-aged persons from the
      general population without CVD, diabetes or chronic kidney disease. The
      dimethylarginines were measured using liquid chromatography tandem mass
      spectrometry (LC-MSMS). Insulin resistance was determined by the homeostasis
      model assessment (HOMA-IR). RESULTS: Asymmetric dimethylarginine (ADMA),
      symmetric dimethylarginine (SDMA), the L-arginine/ADMA ratio and insulin
      resistance were associated with creatinine-based eGFR after accounting for
      measured GFR in multivariable adjusted analyses. The cystatin C-based eGFR showed
      a similar residual association with SDMA; an oppositely directed, borderline
      significant association with ADMA; and a stronger residual association with
      insulin resistance compared with eGFR based on creatinine. CONCLUSION: Both
      creatinine- and cystatin C-based eGFR are influenced by nontraditional risk
      factors, which may bias risk prediction by eGFR in longitudinal studies.

PMID- 25612474
TI  - A new approach to assessing affect and the emotional implications of personal
      genomic testing for common disease risk.
AB  - AIMS: Personal genomic testing (PGT) for common disease risk is becoming
      increasingly frequent, but little is known about people's array of emotional
      reactions to learning their genomic risk profiles and the psychological
      harms/benefits of PGT. We conducted a study of post-PGT affect, including
      positive, neutral, and negative states that may arise after testing. METHODS: A
      total of 228 healthy adults received PGT for common disease variants and
      completed a semistructured research interview within 2 weeks of disclosure. The
      study participants reported how the PGT results made them feel in their own
      words. Using an iterative coding process, the responses were organized into three
      broad affective categories: negative, neutral, and positive affect. RESULTS:
      Neutral affect was the most prevalent response (53.9%), followed by positive
      affect (26.9%) and negative affect (19.2%). We found no differences by gender,
      race, or education. CONCLUSIONS: While <20% of participants reported negative
      affect in response to learning their genomic risk profile for common diseases, a
      majority experienced either neutral or positive emotions. These findings
      contribute to the growing evidence that PGT does not impose significant
      psychological harms. Moreover, they point to a need to better link theories and
      assessments in both emotional and cognitive processing to capitalize on PGT
      information for healthy behavior change.

PMID- 25612476
TI  - Investigating the CFH Gene Polymorphisms as a Risk Factor for Age-related Macular
      Degeneration in an Iranian Population.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a complex disorder which
      results in irreversible vision loss and progressive impairment of central vision.
      Disease susceptibility is influenced by multiple genetic and environmental
      factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene
      are the most important genetic risk factors. We conducted a case-control study to
      investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700
      and rs3753395) of CFH gene with AMD in the Iranian population. MATERIALS AND
      METHODS: We recruited 100 AMD patients and 100 age- and sex-matched normal
      controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395)
      and restriction fragment length polymorphism utilized for rs1061170. Allele and
      genotype frequencies of SNPs were calculated and tested for departure from Hardy
      Weinberg equilibrium using the Chi-square test. An allelic and genotypic
      association was compared by logistic regression analysis using the SNPassoc.
      RESULTS: According to our results, the frequencies of risk allele for all SNPs
      (G, G, A, and C alleles of rs800292, rs2274700, rs3753395 and rs1061170,
      respectively) were significantly higher in AMD patients (p value < 0.001). AMD
      individuals who had at least one copy of the C allele of rs1061170 had an
      increased risk of disease compared with cases with the T allele. Other studied
      polymorphisms showed the same association. CONCLUSION: Our results suggest the
      contribution of all four predicted CFH polymorphisms in AMD susceptibility among
      the Iranian population. This association with CFH may lead to early detection and
      new strategies for prevention and treatment of AMD.

PMID- 25612477
TI  - Modulation of SIRT1-Foxo1 signaling axis by resveratrol: implications in skeletal
      muscle aging and insulin resistance.
AB  - Aging individuals and diabetic patients often exhibit concomitant reductions of
      skeletal muscle mass/strength and insulin sensitivity, suggesting an intimate
      link between muscle aging and insulin resistance. Foxo1, a member of the FOXO
      transcription factor family, is an important player in insulin signaling due to
      its inhibitory role in glucose uptake and utilization in skeletal muscle.
      Phosphorylation of Foxo1 is thought to mitigate the transactivation of pyruvate
      dehydrogenase lipoamide kinase 4 (PDK4), which is a negative regulator of the
      glycolytic enzyme pyruvate dehydrogenase (PDH). In contrast, how aging would
      regulate acetylation/deacetylation machineries and glucose utilization in
      skeletal muscle through the Foxo1/PDH axis remains largely undetermined.
      Accumulating body of evidence have shown that resveratrol, a natural polyphenol
      in grapes and red wine, activates the longevity-related protein sirtuin 1 (SIRT1)
      and augments insulin sensitivity in addition to its well-documented effects on
      mitochondrial energetics. The present review summarizes the role of Foxo1/SIRT1
      in insulin signaling in skeletal muscle and proposes the insight that activation
      of SIRT1 deacetylase activity to deacetylate and suppress the Foxo1-induced
      transactivation of PDK4 may represent an anti-hyperglycemic mechanism of
      resveratrol in aging skeletal muscle.

PMID- 25612478
TI  - Does rat fetal DNA induce preeclampsia in pregnant rats?
AB  - Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is
      unclear whether it is the cause or the consequence of the disease. The aim of
      this study was to prove whether injected rat fetal DNA induces preeclampsia-like
      symptoms in pregnant Wistar rats. They received daily i.p. injections of water or
      rat fetal DNA (400 MUg) from gestation day 14 to 18. Blood pressure, proteinuria,
      placental and fetal weight were measured at gestation day 19. Plasma DNase
      activity, proteinuria and creatinine clearance were assessed. There was no
      significant difference in any of the measured parameters. The results of this
      study do not confirm the hypothesis that fetal DNA might induce preeclampsia.
      This is in contrast to others using human fetal DNA in mice. Further studies
      should be focused on the effects of fetal DNA from the same species protected
      from DNase activity. 

PMID- 25612479
TI  - Transplantation at the grassroots level.

PMID- 25612481
TI  - UW solution: still the "gold standard" for liver transplantation.

PMID- 25612482
TI  - B cell depletion at induction--making bad immunological memory fade?

PMID- 25612483
TI  - What is the definition of a clinically relevant donor HLA-specific antibody
      (DSA)?

PMID- 25612484
TI  - Transplanting hearts in the highly sensitized pediatric candidate: what's a
      program to do?

PMID- 25612485
TI  - Pediatric liver transplantation: is it possible to refrain from using exception
      scores?

PMID- 25612486
TI  - Emerging therapies targeting intra-organ inflammation in transplantation.
AB  - Over the past several years, the field of transplantation has witnessed
      significant progress on several fronts; in particular, achievements have been
      made in devising novel immunosuppressive strategies. An under-explored area that
      may hold great potential to improve transplantation outcomes is the design of
      novel strategies to apply specifically to organs to reduce intra-graft
      inflammation. A growing body of evidence indicates a key role of intra-graft
      inflammatory cascade in potently instigating the alloimmune response. Indeed,
      controlling the activation of innate immunity/inflammatory responses has been
      shown to be a promising strategy to increase the graft acceptance and survival.
      In this minireview, we provide an overview of emerging targeted strategies, which
      can be directly applied to grafts to down-regulate intra-graft inflammation prior
      to transplantation. 

PMID- 25612487
TI  - Advances in the understanding of complement mediated glomerular disease:
      implications for recurrence in the transplant setting.
AB  - Recent advances in the understanding of the role of complement in glomerular
      disease allow for more accurate assessment of the risk of disease recurrence
      after transplantation, and inform the development of targeted treatment
      strategies to overcome specific defects in the alternate pathway of the
      complement system. These advances along with remaining knowledge deficits are
      reviewed with specific relevance to membranoproliferative glomerulonephritis
      (MPGN) and C3 glomerulopathy, a heterogenous group of diseases with a high rate
      of recurrence leading to allograft failure. Recommendations to establish an
      accurate diagnosis and inform therapeutic decision making in transplant
      candidates with a histologic diagnosis of MPGN are provided. 

PMID- 25612488
TI  - What's hot, what's new at WTC--basic science.
AB  - The World Transplant Congress of 2014 presented a broad swath of science that
      touched on many disparate aspects of cell and organ transplantation, molecular
      and cellular immunology, systems biology, development, technology and translation
      into humans. A number of themes emerged this year. B cell biology and antibody
      chemistry were prominent, as they have been for several years. T cells, co
      stimulatory blockade and regulatory T cells continue to dominate many aspects of
      immune research. Many new aspects of monocyte, macrophage, NK cell and NK T cell
      development, biology and regulation are now being explored. Diverse aspects of
      organ injury and the acute and chronic responses to injury are being investigated
      with new techniques, new targets and a resurgent vigor. Novel advances in
      xenotransplantation and experimental tolerance garnered much attention. Newer
      investigations in microbiota and nanotechnology promise significant gains in the
      near future. Lastly the 'omics of DNA, RNA, proteins, metabolites, bacteria and
      enzyme actions promise new understanding in biological systems and how to control
      those systems. 

PMID- 25612489
TI  - What's hot, what's new at WTC--clinical science.
AB  - More than 3000 abstracts of innovative and exciting findings, covering the whole
      field of organ transplantation, were presented at the World Transplant Congress
      2014. Key areas of presentations across all organs and tissues included HLA
      antibodies, antibody-mediated rejection, living donation, immunosuppression,
      organ perfusion and surgical procedures. In addition, cutting edge science and
      future perspectives were presented in state-of-the-art lectures. This review will
      present highlights of this meeting and demonstrate strength and success of
      clinical sciences in transplantation. 

PMID- 25612491
TI  - Normothermic ex vivo perfusion provides superior organ preservation and enables
      viability assessment of hearts from DCD donors.
AB  - The shortage of donors in cardiac transplantation may be alleviated by the use of
      allografts from donation after circulatory death (DCD) donors. We have previously
      shown that hearts exposed to 30 min warm ischemic time and then flushed with
      Celsior supplemented with agents that activate ischemic postconditioning
      pathways, show complete recovery on a blood-perfused ex vivo working heart
      apparatus. In this study, these findings were assessed in a porcine orthotopic
      heart transplant model. DCD hearts were preserved with either normothermic ex
      vivo perfusion (NEVP) using a clinically approved device, or with standard cold
      storage (CS) for 4 h. Orthotopic transplantation into recipient animals was
      subsequently undertaken. Five of six hearts preserved with NEVP demonstrated
      favorable lactate profiles during NEVP and all five could be weaned off
      cardiopulmonary bypass posttransplant, compared with 0 of 3 hearts preserved with
      CS (p < 0.05, Fisher's exact test). In conclusion, DCD hearts flushed with
      supplemented Celsior solution and preserved with NEVP display viability before
      and after transplantation. Viability studies of human DCD hearts using NEVP are
      warranted.

PMID- 25612490
TI  - Bortezomib, C1-inhibitor and plasma exchange do not prolong the survival of multi
      transgenic GalT-KO pig kidney xenografts in baboons.
AB  - Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to
      xenograft rejection, particularly in the context of additional genetic
      modifications. We have performed life supporting kidney xenotransplantation into
      baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons
      received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human
      C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3
      plasma exchanges. One baboon received a control GalT-KO xenograft with the latter
      immunosuppression. All immunosuppressed baboons rejected the xenografts between
      days 9 and 15 with signs of acute humoral rejection, in contrast to untreated
      controls (n = 2) that lost their grafts on days 3 and 4. Immunofluorescence
      analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d
      staining, indicating classical complement pathway blockade but alternate pathway
      activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage
      infiltration with minimal lymphocyte representation. None of the recipients
      showed any signs of porcine endogenous retrovirus transmission but some showed
      evidence of porcine cytomegalovirus (PCMV) replication within the xenografts. Our
      work indicates that the addition of bortezomib and plasma exchange to the
      immunosuppressive regimen did not significantly prolong the survival of multi
      transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative
      complement pathway, innate mechanisms with monocyte activation and PCMV
      replication may have contributed to rejection.

PMID- 25612492
TI  - Compared efficacy of preservation solutions in liver transplantation: a long-term
      graft outcome study from the European Liver Transplant Registry.
AB  - Between 2003 and 2012, 42 869 first liver transplantations performed in Europe
      with the use of either University of Wisconsin solution (UW; N = 24 562),
      histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N =
      7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855)
      preserved grafts. Alternative solutions to the UW were increasingly used during
      the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE
      (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The
      same trend was observed with a total ischemia time (TIT) >12 h or grafts used for
      patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was
      89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate
      analysis identified HTK as an independent factor of graft loss, with recipient
      HIV (+), donor age >=65 years, recipient HCV (+), main disease acute hepatic
      failure, use of a partial liver graft, recipient age >=60 years, no identical ABO
      compatibility, recipient hepatitis B surface antigen (-), TIT >= 12 h, male
      recipient and main disease other than cirrhosis. HTK appears to be an independent
      risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides
      similar results for full size grafts. For partial deceased donor liver grafts,
      IGL-1 tends to offer the best graft outcome.

PMID- 25612493
TI  - Rituximab as induction therapy after renal transplantation: a randomized, double
      blind, placebo-controlled study of efficacy and safety.
AB  - We evaluated the efficacy and safety of rituximab as induction therapy in renal
      transplant patients. In a double-blind, placebo-controlled study, 280 adult renal
      transplant patients were randomized between a single dose of rituximab (375
      mg/m(2)) or placebo during transplant surgery. Patients were stratified according
      to panel-reactive antibody (PRA) value and rank number of transplantation.
      Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil and
      steroids. The primary endpoint was the incidence of biopsy proven acute rejection
      (BPAR) within 6 months after transplantation. The incidence of BPAR was
      comparable between rituximab-treated (23/138, 16.7%) and placebo-treated patients
      (30/142, 21.2%, p = 0.25). Immunologically high-risk patients (PRA >6% or re
      transplant) not receiving rituximab had a significantly higher incidence of
      rejection (13/34, 38.2%) compared to other treatment groups (rituximab-treated
      immunologically high-risk patients, and rituximab- or placebo-treated
      immunologically low-risk (PRA <= 6% or first transplant) patients (17.9%, 16.4%
      and 15.7%, p = 0.004). Neutropenia (<1.5 * 10(9) /L) occurred more frequently in
      rituximab-treated patients (24.3% vs. 2.2%, p < 0.001). After 24 months, the
      cumulative incidence of infections and malignancies was comparable. A single dose
      of rituximab as induction therapy did not reduce the overall incidence of BPAR,
      but might be beneficial in immunologically high-risk patients. Treatment with
      rituximab was safe.

PMID- 25612494
TI  - Survival in sensitized lung transplant recipients with perioperative
      desensitization.
AB  - Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long
      term lung transplant outcomes. We implemented a perioperative strategy to treat
      DSA-positive recipients, leading to equivalent rejection and graft survival
      outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens.
      DSA-positive patients were transplanted if panel reactive antibody (PRA) >=30% or
      medically urgent and desensitized with perioperative plasma exchange, intravenous
      immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA
      positive/DSA-negative recipients received MPA. Unsensitized patients received
      routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011,
      340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA
      positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96%
      in the three groups, respectively. One-year graft survival was 89%/88%/86% (p =
      0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to
      experience any >= grade 2 acute rejection (9% and 9% vs. 18% unsensitized p =
      0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and
      predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were
      equivalent between groups. With the application of this perioperative treatment
      protocol, lung transplantation can be safely performed in DSA/PRA-positive
      patients, with similar outcomes to unsensitized recipients.

PMID- 25612495
TI  - Comparison of listing strategies for allosensitized heart transplant candidates
      requiring transplant at high urgency: a decision model analysis.
AB  - Allosensitized children who require a negative prospective crossmatch have a high
      risk of death awaiting heart transplantation. Accepting the first suitable organ
      offer, regardless of the possibility of a positive crossmatch, would improve
      waitlist outcomes but it is unclear whether it would result in improved survival
      at all times after listing, including posttransplant. We created a Markov
      decision model to compare survival after listing with a requirement for a
      negative prospective donor cell crossmatch (WAIT) versus acceptance of the first
      suitable offer (TAKE). Model parameters were derived from registry data on status
      1A (highest urgency) pediatric heart transplant listings. We assumed no
      possibility of a positive crossmatch in the WAIT strategy and a base-case
      probability of a positive crossmatch in the TAKE strategy of 47%, as estimated
      from cohort data. Under base-case assumptions, TAKE showed an incremental
      survival benefit of 1.4 years over WAIT. In multiple sensitivity analyses,
      including variation of the probability of a positive crossmatch from 10% to 100%,
      TAKE was consistently favored. While model input data were less well suited to
      comparing survival when awaiting transplantation across a negative virtual
      crossmatch, our analysis suggests that taking the first suitable organ offer
      under these circumstances is also favored.

PMID- 25612496
TI  - Heterogeneity and disparities in the use of exception scores in pediatric liver
      allocation.
AB  - Physicians apply for Model for End-Stage Liver Disease/Pediatric End-Stage Liver
      Disease exception points on a case-by-case basis to improve an individual
      patient's chances of receiving a liver transplant. This retrospective cohort
      study describes trends in the use of exceptions among the pediatric liver
      waitlist population with chronic liver disease. The cohort (n = 3728) included
      all children with a diagnosis of chronic liver disease listed in the United
      Network for Organ Sharing transplant database for first isolated liver transplant
      between February 27, 2002 and March 31, 2013. Exception score requests were
      common (34%); 90% of requests were approved. The rate of exception score requests
      in 2013 was five times that of 2002 (incident rate ratios [IRR] 5.25, 95%
      confidence interval [CI] 3.19-8.63, p < 0.01). Patients of non-White race had
      exception score request rates 13% lower than patients of White race (IRR 0.87,
      95% CI 0.77-0.98, p = 0.02). Older patients had lower rates of exception score
      requests than younger patients (p = 0.03). Request rates varied by region. Time
      spent at an active exception status nearly tripled the hazard rate for
      transplantation (hazard ratio = 2.90, 95% CI 2.62-3.21, p < 0.01). There is
      disparity in use of exceptions by race that is not explained by clinical disease
      severity, diagnosis, geography or other demographic factors.

PMID- 25612497
TI  - Loss of pediatric kidney grafts during the "high-risk age window": insights from
      pediatric liver and simultaneous liver-kidney recipients.
AB  - Pediatric kidney transplant recipients experience a high-risk age window of
      increased graft loss during late adolescence and early adulthood that has been
      attributed primarily to sociobehavioral mechanisms such as nonadherence. An
      examination of how this age window affects recipients of other organs may inform
      the extent to which sociobehavioral mechanisms are to blame or whether kidney
      specific biologic mechanisms may also exist. Graft loss risk across current
      recipient age was compared between pediatric kidney (n = 17,446), liver (n =
      12,161) and simultaneous liver-kidney (n = 224) transplants using piecewise
      constant hazard rate models. Kidney graft loss during late adolescence and early
      adulthood (ages 17-24 years) was significantly greater than during ages <17 (aHR
      = 1.79, 95%CI = 1.69-1.90, p < 0.001) and ages >24 (aHR = 1.11, 95%CI = 1.03
      1.20, p = 0.005). In contrast, liver graft loss during ages 17-24 was no
      different than during ages <17 (aHR = 1.03, 95%CI = 0.92-1.16, p = 0.6) or ages
      >24 (aHR = 1.18, 95%CI = 0.98-1.42, p = 0.1). In simultaneous liver-kidney
      recipients, a trend towards increased kidney compared to liver graft loss was
      observed during ages 17-24 years. Late adolescence and early adulthood are less
      detrimental to pediatric liver grafts compared to kidney grafts, suggesting that
      sociobehavioral mechanisms alone may be insufficient to create the high-risk age
      window and that additional biologic mechanisms may also be required.

PMID- 25612498
TI  - Uric acid and the risk of graft failure in kidney transplant recipients: a re
      assessment.
AB  - The association of hyperuricemia with kidney allograft outcomes remains
      controversial. We studied this problem in 1170 kidney transplants from January
      2000 to December 2010. The primary endpoint was total graft failure (i.e. graft
      loss or death). Conventional, time-dependent and marginal structural Cox
      proportional hazards models were fitted, the latter accounting for kidney
      function as a time-varying confounder affected by prior uric acid levels. Uric
      acid level was associated with an increased risk of total graft failure in time
      fixed and time-varying models (HR 1.02 [95% CI: 1.003-1.04] and HR 1.02 [95% CI:
      1.01-1.03], respectively, for every 10 umol/L increase in uric acid). In
      contrast, the marginal structural model showed a modestly protective effect (HR
      0.90 [95% CI: 0.85-0.94] for every 10 umol/L increase in uric acid). Similar
      results were observed for death-censored graft failure and death with graft
      function. In summary, the absence of a deleterious association between elevated
      uric acid and graft outcome after accounting for graft function as a time-varying
      confounder suggests that uric acid is not an independent risk factor for graft
      failure. The modestly protective effect of uric acid may be an indicator of
      nutritional status but further study is warranted.

PMID- 25612499
TI  - The independent living donor advocate: a guidance document from the American
      Society of Transplantation's Living Donor Community of Practice (AST LDCOP).
AB  - The independent living donor advocate (ILDA) serves a mandated and supportive
      role in the care of the living organ donor, yet qualifications and role
      requirements are not clearly defined. Guidance comes from Centers for Medicare
      and Medicaid Services (CMS) Conditions for Transplant Center Participation and
      interpretive guidelines, Organ Procurement and Transplantation Network (OPTN)
      Policy and CMS and OPTN site surveys, yet interpretation of regulations varies.
      Herein, the AST Living Donor Community of Practice (LDCOP) offers seven
      recommendations to clarify and optimize the ILDA role: (a) the ILDA must have a
      certain skill set rather than a specific profession, (b) the ILDA must be
      educated and demonstrate competence in core knowledge components, (c) the ILDA's
      primary role is to assess components of informed consent, (d) centers must
      develop a transparent system to define ILDA independence, (e) the ILDA should
      have a reporting structure outside the transplant center, (f) the ILDA's role
      should be integrated throughout the donor care continuum, (g) the ILDA role
      should include a narrow "veto power." We address controversies in ILDA
      implementation, and offer pathways to maximize benefits and minimize limitations
      of approaches that may each meet regulatory requirements but confer different
      practice benefits. We propose a research agenda to explore the impact of the
      ILDA.

PMID- 25612500
TI  - Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody
      mediated rejection (AMR): a multicenter pilot study from the AECVP.
AB  - This multicenter case-controlled pilot study evaluated myocardial inflammatory
      burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without
      pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European
      heart transplant centers were centrally reviewed as positive (grade 2, n = 28),
      suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of
      total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear
      cells were correlated with pAMR grade, capillary C4d deposition, donor specific
      antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies,
      equivalent number of IV CD3+ T lymphocytes (23 +/- 4/0.225 mm(2) ) and CD68+
      macrophages (21 +/- 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated
      with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of
      IV T lymphocytes were associated with low grade ACR (p = 0.002). In late
      occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with
      higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA
      positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were
      found. The presence of plasma cells was associated with a higher IB and
      occurrence of pAMR late after transplantation.

PMID- 25612501
TI  - The impact of proposed changes in liver allocation policy on cold ischemia times
      and organ transportation costs.
AB  - Changes to the liver allocation system have been proposed to decrease regional
      variation in access to liver transplant. It is unclear what impact these changes
      will have on cold ischemia times (CITs) and donor transportation costs.
      Therefore, we performed a retrospective single center study (2008-2012) measuring
      liver procurement CIT and transportation costs. Four groups were defined: Local
      within driving distance (Local-D, n = 262), Local-flight (Local-F, n = 105),
      Regional-flight <3 h (Regional <3 h, n = 61) and Regional-Flight >3 h (Regional
      >3 h, n = 53). The median travel distance increased in each group, varying from
      zero miles (Local-D), 196 miles (Local-F), 384 miles (Regional <3 h), to 1647
      miles (Regional >3 h). Increasing travel distances did not significantly increase
      CIT until the flight time was >3 h. The average CIT ranged from 5.0 to 6.0 h for
      Local-D, Local-F and Regional <3 h, but increased to 10 h for Regional >3 h (p <
      0.0001). Transportation costs increased with greater distance traveled: Local-D
      $101, Local-F $1993, Regional <3 h $8324 and Regional >3 h $27 810 (p < 0.0001).
      With proposed redistricting, local financial modeling suggests that the average
      liver donor procurement transportation variable direct costs will increase from
      $2415 to $7547/liver donor, an increase of 313%. These findings suggest that
      further discussion among transplant centers and insurance providers is needed
      prior to policy implementation.

PMID- 25612502
TI  - Transfusion transmitted infections in solid organ transplantation.
AB  - While the risk of infectious disease transmission through blood transfusion has
      been greatly reduced as a result of improved screening methods, transfusion
      transmissible infections remain a concern for transplant recipients, especially
      those receiving multiple transfusions. Although transfusion and transplant
      recipients are at risk for similar infections, the current reporting requirements
      for infections transmitted by transfusions and organ transplantation vary greatly
      and remain distinctly separate with no communication between reporting systems.
      This article reviews 23 past reports of transfusion-transmitted infections in
      organ recipients acquired through transfusions. While cytomegalovirus was a major
      focus of such reports in the 1980s, more recent reports have focused on West Nile
      virus transmission. Additionally, this article highlights challenges in
      determining transfusion-transmitted infection risk in transplant recipients
      related to the current reporting systems. 

PMID- 25612504
TI  - Early graft dysfunction after lung transplantation.

PMID- 25612506
TI  - Antidepressant dose of taurine increases mRNA expression of GABAA receptor alpha2
      subunit and BDNF in the hippocampus of diabetic rats.
AB  - Diabetes mellitus is a metabolic disorder associated with higher risk for
      depression. Diabetic rats present depressive-like behaviors and taurine, one of
      the most abundant free amino acids in the brain, reverses this depressive
      behaviors. Because taurine is a GABAA agonist modulator, we hypothesize that its
      antidepressant effect results from the interaction on this system by changing
      alpha2 GABAA receptor subunit expression, beside changes on BDNF mRNA, and memory
      in diabetic rats. Streptozotocin-diabetic and non-diabetic Wistar rats were daily
      injected with 100mg/kg of taurine or saline, intraperitoneally, for 30 days. At
      the end of the experiment, rats were exposed to the novel object recognition
      memory. Later they were euthanized, the brains were weighed, and the hippocampus
      was dissected for alpha2 GABAA subunit and BDNF mRNA expression. Real-time
      quantitative PCR (qPCR) showed that diabetic rats presented lower alpha2 GABAA
      subunit and BDNF mRNA expression than non-diabetic rats and taurine increased
      both parameters in these sick rats. Taurine also reversed the lower brain weight
      and improved the short-term memory in diabetic rats. Thus, the taurine
      antidepressant effect may be explained by interference with the GABA system, in
      line to its neuroprotective effect showed here by preventing brain weight loss
      and improving memory in diabetic rats.

PMID- 25612507
TI  - Toward oral delivery of biopharmaceuticals: an assessment of the gastrointestinal
      stability of 17 peptide drugs.
AB  - A major barrier to successful oral delivery of peptide and protein molecules is
      their inherent instability in the lumen of the gastrointestinal tract. The aim of
      this study was to determine the stability of 17 disparate peptide drugs (insulin,
      calcitonin, glucagon, secretin, somatostatin, desmopressin, oxytocin, [Arg(8)]
      vasopressin, octreotide, ciclosporin, leuprolide, nafarelin, buserelin,
      histrelin, [d-Ser](4)-gonadorelin, deslorelin, and goserelin) in gastric and
      small intestinal fluids from both humans and pigs, and in simulated gastric and
      intestinal fluids. In human gastric fluid, the larger peptides including
      somatostatin, calcitonin, secretin, glucagon, and insulin were metabolized
      rapidly, while the smaller peptides showed good stability. In human small
      intestinal fluid, however, both small and large peptides degraded rapidly with
      the exception of the cyclic peptide ciclosporin and the disulfide-bridge
      containing peptides octreotide and desmopressin, which showed good stability. The
      stability of peptides in both simulated gastric fluid and pig gastric fluid
      correlated well with stability in human gastric fluid. However, it was not
      possible to establish such a correlation with the small intestinal fluids because
      of the rapid rate of peptide degradation. This work has identified the molecular
      features in the structure of a wide range of peptides that influence their
      stability in the environment of the gastrointestinal tract, which in turn will
      allow for better selection of peptide candidates for oral delivery. 

PMID- 25612508
TI  - GTV delineation in supraglottic laryngeal carcinoma: interobserver agreement of
      CT versus CT-MR delineation.
AB  - BACKGROUND: GTV delineation is the first crucial step in radiotherapy and
      requires high accuracy, especially with the growing use of highly conformal and
      adaptive radiotherapy techniques. If GTV delineations of observers concord, they
      are considered to be of high accuracy. The aim of the study is to determine the
      interobserver agreement for GTV delineations of supraglottic laryngeal carcinoma
      on CT and on CT combined with MR-images and to determine the effect of adding MR
      images to CT-based delineation on the delineated volume and the interobserver
      agreement. METHODS: Twenty patients with biopsy proven T1-T4 supraglottic
      laryngeal cancer, treated with curative intent were included. For all patients a
      contrast enhanced planning CT and a 1.5-T MRI with gadolinium were acquired in
      the same head-and-shoulder mask for fixation as used during treatment. For MRI, a
      two element surface coil was used as a receiver coil. Three dedicated observers
      independently delineated the GTV on CT. After an interval of 2 weeks, a set of co
      registered CT and MR-images was provided to delineate the GTV on CT. Common
      volumes (C) and encompassing volumes (E) were calculated and C/E ratios were
      determined for each pair of observers. The conformity index general (CIgen) was
      used to quantify the interobserver agreement. RESULTS: In general, a large
      variation in interobserver agreement was found for CT (range: 0.29-0.77) as well
      as for CT-MR delineations (range: 0.17-0.80). The mean CIgen for CT (0.61) was
      larger compared to CT-MR (0.57) (p = 0.032). Mean GTV volume delineated on CT-MR
      (6.6 cm(3)) was larger compared to CT (5.6 cm(3)) (p = 0.002). CONCLUSION:
      Delineation on CT with co-registered MR-images resulted in a larger mean GTV
      volume and in a decrease in interobserver agreement compared to CT only
      delineation for supraglottic laryngeal carcinoma.

PMID- 25612509
TI  - Influence of human activities on the historical and current distribution of
      Sichuan snub-nosed monkeys in the Qinling Mountains, China.
AB  - Due to their rich animal diversity and the presence of rare and endemic species,
      the Qinling Mountains are listed as a significant global biodiversity area. The
      Sichuan snub-nosed monkey (Rhinopithecus roxellana) has been distributed in this
      area since the Middle Pleistocene. Due to the gradual encroachment of humans into
      their habitat, both the distribution range and population sizes of R. roxellana
      have significantly decreased. Based on literature research as well as field and
      questionnaires, we investigated the influence of human activities on R. roxellana
      distribution in the Qinling Mountains. Human activity within the habitat of R.
      roxellana began in the Stone and Bronze Ages, though initially it had no
      significant influence on its populations. When China entered the Iron Age,
      however, different historical and social periods had a considerable impact on R.
      roxellana distribution. Although national and provincial level governments
      introduced strict protection policies with the establishment of the People's
      Republic of China in 1949, human activities continued to influence R. roxellana
      distribution. Since the launch of the Natural Forest Protection Project across
      the Qinling Mountains in 1999, the quality of R. roxellana habitat has shown
      marked improvement. This research will help promote the survival and conservation
      of the Sichuan snub-nosed monkey in the Qinling Mountains.

PMID- 25612510
TI  - Molecular insights into the possible role of Kir4.1 and Kir5.1 in thyroid hormone
      biosynthesis.
AB  - INTRODUCTION: Thyroid morphogenesis is a complex process. Inwardly rectifying
      potassium (Kir) genes play a role in hormone release, cell excitability, pH and
      K(+) homeostasis in many tissues. OBJECTIVES: To investigate the thyroid
      developmental expression of three members, Kir4.1, Kir4.2 and Kir5.1, in mice. To
      postulate the K(+) channel role in thyroid hormone secretion. MATERIAL AND
      METHODS: Quantitative RT-PCR analysis of Kir4.1, Kir4.2 and Kir5.1 in mice of
      different stages (E13.5-E18.5). RESULTS: mRNA for Kir4.1, Kir4.2 and Kir5.1 were
      identified and increased with age in mice. Both Kir4.1 and Kir4.2 genes are
      better expressed after E16.5. Kir4.2 greatly increases from E13.5 to E16.5 (p <=
      0.05). CONCLUSION: Quantitative PCR shows that the mouse thyroid presents
      increased expression for Kir channels during development. The role of Kir in
      thyroid morphogenesis and differentiation might be understood in future studies.
      We speculate that thyroglobulin trafficking might be modulated by Kir4.1/5.1.

PMID- 25612512
TI  - Vertical patient flow: is it safe and effective?

PMID- 25612511
TI  - Expression of ROS1 predicts ROS1 gene rearrangement in inflammatory
      myofibroblastic tumors.
AB  - Inflammatory myofibroblastic tumor is a distinctive, rarely metastasizing
      mesenchymal neoplasm composed of fascicles of spindle cells with a prominent
      inflammatory infiltrate. Roughly 50% of inflammatory myofibroblastic tumors
      harbor ALK receptor tyrosine kinase gene rearrangements. Such tumors are usually
      positive for ALK by immunohistochemistry. The molecular pathogenesis of ALK
      negative inflammatory myofibroblastic tumors is largely unknown. A recent study
      identified rearrangements of ROS1 (another tyrosine kinase receptor) in a subset
      of ALK-negative inflammatory myofibroblastic tumors. Immunohistochemistry for
      ROS1 has been shown to correlate with ROS1 rearrangement in lung adenocarcinomas.
      The purpose of this study was to determine whether immunohistochemistry for ROS1
      could predict ROS1 rearrangement in inflammatory myofibroblastic tumor. In total,
      30 inflammatory myofibroblastic tumors were evaluated, including 21 ALK-positive
      tumors (10 confirmed to harbor ALK rearrangements, with TPM3, CLTC, RANPB2, and
      FN1 fusion partners) and 9 ALK-negative tumors (including 2 known to harbor ROS1
      rearrangements). Immunohistochemistry was performed on whole tissue sections
      following pressure cooker antigen retrieval using a rabbit anti-ROS1 monoclonal
      antibody. The results were scored as 'positive' or 'negative,' and the pattern of
      staining was recorded. Three ALK-negative inflammatory myofibroblastic tumors
      (including both tumors with known ROS1 rearrangements) showed immunoreactivity
      for ROS1, whereas all ALK-positive inflammatory myofibroblastic tumors were
      negative for ROS1. One ROS1-positive inflammatory myofibroblastic tumor (with
      YWHAE-ROS1 fusion) showed strong, diffuse cytoplasmic and nuclear staining; one
      case (with TFG-ROS1 fusion) showed weak, diffuse and dot-like cytoplasmic
      staining; and one case (fusion partner unknown) showed moderate, diffuse and dot
      like cytoplasmic staining. Expression of ROS1 correlates with ROS1 gene
      rearrangement in inflammatory myofibroblastic tumor. These findings suggest that
      immunohistochemistry for ROS1 may be useful to support the diagnosis of a subset
      of inflammatory myofibroblastic tumors and may select some clinically aggressive
      cases for targeted therapy directed against ROS1. 

PMID- 25612513
TI  - Keep it clean: a visual approach to reinforce hand hygiene compliance in the
      emergency department.
AB  - PROBLEM: Although hand hygiene strategies significantly reduce health care
      associated infections, multiple studies have documented that hand hygiene is the
      most overlooked and poorly performed infection control intervention. METHODS:
      Emergency nurses and technicians (n = 95) in a 41-bed emergency department in
      eastern Virginia completed pretests and posttests, an education module, and two
      experiential learning activities reinforcing hand hygiene and infection control
      protocols. RESULTS: Posttest scores were significantly higher than pretest scores
      (t (108) = -6.928, P = .048). Hand hygiene compliance rates improved at the
      conclusion of the project and 3 months after the study (F (2, 15) = 9.89, P =
      .002). IMPLICATIONS FOR PRACTICE: Interfaces with staff as they completed the
      interactive exercise, as well as anecdotal notes collected during the study,
      identified key times when compliance suffered and offered opportunities to
      further improve hand hygiene and, ultimately, patient safety.

PMID- 25612514
TI  - Infections in trauma patients: prevention begins in the emergency department.

PMID- 25612515
TI  - Recognizing and responding to a new era of infectious and communicable diseases.

PMID- 25612516
TI  - Impact of nurse-initiated ED sepsis protocol on compliance with sepsis bundles,
      time to initial antibiotic administration, and in-hospital mortality.
AB  - INTRODUCTION: Emergency nurses play a key role in the initial triage and care of
      patients with potentially life-threatening illnesses. The aims of this study were
      to (1) evaluate the impact of a nurse-initiated ED sepsis protocol on time to
      initial antibiotic administration, (2) ascertain compliance with 3-hour Surviving
      Sepsis Campaign (SSC) targets, and (3) identify predictors of in-hospital sepsis
      mortality. METHODS: A retrospective chart review investigated all adult patients
      admitted through either of 2 academic tertiary medical center emergency
      departments-who were discharged with a diagnosis of severe sepsis or septic shock
      (N = 195). Pre- and post-protocol implementation data examined both compliance
      with 3-hour SSC bundle targets and patient outcomes. Multivariate logistic
      regression analysis identified predictors of in-hospital mortality. RESULTS:
      Serum lactate measurement (83.9% vs 98.7%, P = .003) and median time to initial
      antibiotic administration (135 minutes vs 108 minutes, P = .021) improved
      significantly after protocol implementation. However, one quarter of antibiotic
      administration times still exceeded the 3-hour target. Significant predictors of
      in-hospital mortality were respiratory dysfunction, central nervous system
      dysfunction, urinary tract infection, vasopressor administration, and patient
      body weight (P < .05). There were no in-hospital mortality rate differences
      between the pre- and post-protocol implementation groups. DISCUSSION: Compliance
      with serum lactate measurement and blood culture collection goals approached 100%
      in the post-protocol group. However, compliance with medical interventions
      requiring multiple health care-provider involvement (ie, antibiotic and fluid
      administration) remained suboptimal. Efforts focused on multidisciplinary bundle
      elements are necessary to achieve full compliance with SSC targets.

PMID- 25612517
TI  - Are you covered? Safe practices for the use of personal protective equipment.

PMID- 25612518
TI  - Effect of a high-fat diet on the hepatic expression of nuclear receptors and
      their target genes: relevance to drug disposition.
AB  - More than 1.4 billion individuals are overweight or obese worldwide. While
      complications often require therapeutic intervention, data regarding the impact
      of obesity on drug disposition are scarce. As the influence of diet-induced
      obesity on drug transport and metabolic pathways is currently unclear, the
      objective of the present study was to investigate the effect of high fat feeding
      for 13 weeks in female Sprague-Dawley rats on the hepatic expression of the
      nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor
      (CAR), liver X receptor (LXR) and farnesoid X receptor (FXR) and several of their
      target genes. We hypothesised that high fat feeding would alter the gene
      expression of major hepatic transporters through a dysregulation of the
      expression of the nuclear receptors. The results demonstrated that, along with a
      significant increase in body fat and weight, a high-fat diet (HFD) induced a
      significant 2-fold increase in the expression of PXR as well as a 2-, 5- and 2.5
      fold increase in the hepatic expression of the PXR target genes Abcc2, Abcb1a and
      Cyp3a2, respectively (P< 0.05). The expression levels of FXR were significantly
      increased in rats fed a HFD in addition to the increase in the expression levels
      of FXR target genes Abcb11 and Abcb4. The expression levels of both LXRalpha and
      LXRbeta were slightly but significantly increased in rats fed a HFD, and the
      expression levels of their target genes Abca1 and Abcg5, but not Abcg8, were
      significantly increased. The expression of the nuclear receptor CAR was not
      significantly altered between the groups. This suggests that a HFD may induce
      changes in the hepatobiliary transport and metabolism of endogenous and exogenous
      compounds. 

PMID- 25612519
TI  - Is Prolonged Operation Time a Predictor for the Occurrence of Complications in
      Ureteroscopy?
AB  - OBJECTIVE: To determine the impact of duration of ureteroscopy for urolithiasis
      on complication rates (CRs) of the procedure. METHODS: A retrospective analysis
      of 2,010 patients, treated between 2006 and 2011, was done. The operation time
      (OT) and the occurrence of complications were compared. RESULTS: The overall CR
      was 14.3% [298 complications, minor complications (Clavien I-II) 91.7%]. The
      median OT was 35 min [interquartile range (IQR) 20-61]. The OT differed
      significantly between those without complications [34 min (IQR 20-60)] and those
      with complications [45 min (IQR 25-76)] (p < 0.0001). The correlation between the
      OT and the occurrence of complications (r = -0.009648, p < 0.0001) was very weak
      and passed the level of significance (r = 0.2). The effect size was of minor
      relevance (Cohen's d = 0.27972). CONCLUSIONS: Longer OT correlates significantly
      with a higher CR. The effect is however shown to be minor and the overall rate of
      complications, especially severe ones, is low.

PMID- 25612520
TI  - Analysis of altered microRNA expression profile in the reparative interface of
      the femoral head with osteonecrosis.
AB  - The reparative reaction is considered to be important during the occurrence of
      collapse in the femoral head with osteonecrosis (ONFH), but little is known about
      the long-term reparative process. The aim of this study was to determine and
      analyze the altered microRNA expression profile in the reparative interface of
      ONFH, and further validate the expression of the involved genes in the predicted
      pathways. Microarray analysis was performed comparing the reparative interface of
      patients with ONFH and normal tissue of patients with fresh femoral neck fracture
      (FNF) and partly validated by real-time PCR. Potential target genes of
      differentially expressed miRNAs were predicted by TargetScan and miRanda, and the
      target genes were used for further bioinformatics analysis such as Gene Ontology
      and Pathway assay. The filtered miRNAs and genes in the predict pathways were
      further examined by real-time PCR in another 6 independent ONFH patients. Among
      the 2578 miRNAs identified, 17 were consistently differentially expressed, 12 of
      which are up-regulated and 5 down-regulated. GO classification showed that the
      predicted target genes of these miRNAs are involved in signal transduction, cell
      differentiation, methylation, cell growth and apoptosis. The Kyoto Encyclopedia
      of Genes and Genomes (KEGG) classification indicated that these genes play a role
      in angiogenesis and Wnt signaling pathways. The expression of miR-34a and miR
      146a and genes in the predict pathways were significantly up-regulated. This
      study presented a global view of miRNA expression in the reparative interface of
      osteonecrosis. In addition, our data provided novel and robust information for
      further researches in the pathogenesis and molecular events of ONFH. 

PMID- 25612521
TI  - "Core out" or "curettage" in rectal advancement flap for cryptoglandular anal
      fistula.
AB  - AIM: Transanal advancement flap is a recognized technique for complex fistula.
      Management of the tract is open to discussion. Excision of the tract by the "core
      out" technique is difficult and could increase the risk of sphincter damage.
      Curettage is easier but it could increase the risk of recurrence. The aim of the
      present study was to assess the effect of both techniques on sphincter function
      and to study the clinical results. METHOD: This is a retrospective analysis from
      a prospective database. One hundred nineteen consecutive patients with high
      cryptoglandular anal fistula were included. "Core out" technique was performed in
      78 patients (group I) and "curettage" in 41 (group II). In both, a full-thickness
      rectal flap was advanced over the closed internal defect. Anorectal manometry was
      performed to assess sphincter function. Continence was assessed using the Wexner
      Scale. Recurrence was defined as the presence of an abscess or fistulization.
      RESULTS: Manometric results showed a significant decrease in the maximum resting
      pressure after surgery in both groups. The maximum squeeze pressure was
      significantly reduced only in group I (p < 0.001). No significant changes in
      Wexner score were observed. The overall recurrence rate was 5.88%, five of group
      I (6.4%) and two of group II (4.9%), without statistical significance (p = 0.74).
      CONCLUSIONS: The core-out technique causes a significant decrease in squeeze
      pressures, which reflects damage to the external anal sphincter. This could lead
      to incontinence in high-risk patients. Curettage is a simple technique that
      preserves the values of squeeze pressures without increasing recurrence rates.

PMID- 25612522
TI  - Altered volatile profile associated with precopulatory mate guarding attracts
      spider mite males.
AB  - Proximate factors affecting animal behavior include stimuli generated by
      conspecifics. In spider mites of the genus Tetranychus (Acari: Tetranychidae),
      males guard pre-reproductive quiescent females, because only the first mating
      results in fertilization. In a dual-choice experiment, more adult males of T.
      urticae were attracted to females guarded by a male than to solitary females.
      Because spider mites are known to perceive volatiles, we hypothesized that
      guarded and solitary females differ in the volatile blends emitted. To test this
      hypothesis, headspace volatiles of guarded females, solitary females, and
      solitary males were collected, respectively. GC/MS analysis detected octanal,
      methyl salicylate, ethyl 4-ethoxybenzoate, and methyl cis-dihydrojasmonate in all
      of the groups. Orthogonal Projection to Latent Structures Discriminant Analysis
      (OPLS-DA) of the blends clearly discriminated guarded females from solitary
      females, supporting our hypothesis. Individual compounds did not show significant
      difference in emission rates for guarded females vs. solitary females, suggesting
      that differences lay in the total blend composition. OPLS-DA did not discriminate
      between the blends emitted by guarded females and solitary males. In conclusion,
      the differences in the volatile blends are likely to mediate male discrimination
      between guarded and solitary females. 

PMID- 25612523
TI  - Stent thrombosis with biodegradable polymer drug-eluting stents versus durable
      polymer sirolimus-eluting stents: an update meta-analysis.
AB  - OBJECTIVE: Durable polymer sirolimus-eluting stents (DP-SES) are associated with
      a low risk of stent thrombosis; biodegradable polymer drug-eluting stents (BP
      DES) were designed to reduce these risks. However, their benefits are still
      variable. METHOD: We undertook a meta-analysis of randomized trials identified by
      systematic searches of Medline, Embase, and the Cochrane Database. RESULTS:
      Eleven studies (9,676 patients) with a mean follow-up of 22.6 months were
      included. Overall, compared with DP-SES, BP-DES significantly lowered the rate of
      definite or probable stent thrombosis (RR, 0.73; 95% CI, 0.55-0.97; p = 0.03;
      I(2) = 0.0%) due to a decreased risk of very late stent thrombosis (RR, 0.26; 95%
      CI, 0.11-0.63; p = 0.00; I(2) = 0.0%). However, BP-DES were associated with a
      comparable rate of early and late stent thrombosis. Meanwhile, BP-DES were
      associated with a broadly equivalent risk of target vessel revascularization (RR,
      0.90; 95% CI, 0.78-1.03; p = 0.13; I(2) = 0.0%), cardiac death (RR, 0.89; 95% CI,
      0.72-1.09; p = 0.24; I(2) = 0.0%), myocardial infarction (RR, 1.03; 95% CI, 0.84
      1.26; p = 0.79; I(2) = 0.0%), and major adverse cardiac events (MACE; RR, 0.91;
      95% CI, 0.83-1.0; p = 0.08; I(2) = 0.0%). Furthermore, angiographic data showed
      that in-stent and in-segment late luminal loss were similar between the two
      groups. CONCLUSIONS: Compared with DP-SES, BP-DES were associated with a lower
      rate of very late stent thrombosis and an equivalent risk of MACE. Larger
      randomized studies are needed to confirm this finding.

PMID- 25612537
TI  - Hypnotizing Libet: Readiness potentials with non-conscious volition.
AB  - The readiness potential (RP) is one of the most controversial topics in
      neuroscience and philosophy due to its perceived relevance to the role of
      conscious willing in action. Libet and colleagues reported that RP onset precedes
      both volitional movement and conscious awareness of willing that movement,
      suggesting that the experience of conscious will may not cause volitional
      movement (Libet, Gleason, Wright, & Pearl, 1983). Rather, they suggested that the
      RP indexes unconscious processes that may actually cause both volitional movement
      and the accompanying conscious feeling of will (Libet et al., 1983; pg. 640).
      Here, we demonstrate that volitional movement can occur without an accompanying
      feeling of will. We additionally show that the neural processes indexed by RPs
      are insufficient to cause the experience of conscious willing. Specifically, RPs
      still occur when subjects make self-timed, endogenously-initiated movements due
      to a post-hypnotic suggestion, without a conscious feeling of having willed those
      movements. 

PMID- 25612538
TI  - Embedded synaptic feedback in the neuroendocrine stress axis.
AB  - Neural regulation of blood glucocorticoid levels is critical for defence of
      homeostasis during physiological or psychoemotional challenges. In mammals, this
      function is carried out by the neuroendocrine stress axis, coordinated by
      parvocellular neuroendocrine cells (PNCs) of the paraventricular hypothalamic
      nucleus. Feedback regulation of PNCs by glucocorticoids provides complex
      experience-dependent shaping of neuroendocrine responses. We review recent
      evidence for metaplastic actions of glucocorticoids as 'circuit breakers' at
      synapses directly regulating PNC excitability and explore how such mechanisms may
      serve as substrates for stress adaptation. 

PMID- 25612539
TI  - Cardiovascular safety of new oral anticoagulants: re-analysis of 27 randomized
      trials based on Bayesian network meta-analysis.

PMID- 25612540
TI  - Monitoring the distribution of surfactants in the stratum corneum by combined ATR
      FTIR and tape-stripping experiments.
AB  - Combined ATR-FTIR (attenuated total reflection-Fourier transform infrared)
      spectroscopy and tape-stripping experiments in vitro on porcine ear skin were
      used to investigate the spatial distribution of different surfactants in the
      stratum corneum (SC). To reveal a possible connection between the size of the
      formed micelles and skin penetration, dynamic light-scattering measurements of
      the aqueous surfactant solutions were also taken. Compared to an alkyl
      polyglycoside and sucrose laurate, a deeper skin penetration of the anionic
      surfactants sodium dodecyl sulfate (SDS) und sodium lauryl ether sulfate (SLES)
      could be related to a smaller size of the formed micelles. Beside the differences
      in spatial distribution, a link between the physical presence of anionic
      surfactants in the SC and a decrease of skin hydration was found. Furthermore,
      the incorporation of SDS and SLES into the SC, even after a brief, consumer
      orientated washing procedure with commercially available hair shampoos, was
      confirmed.

PMID- 25612541
TI  - Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor
      chaperone, against noise-induced hearing loss.
AB  - The sigma-1 receptor, which is expressed throughout the brain, provides
      physiological benefits that include higher brain function. The sigma-1 receptor
      functions as a chaperone in the endoplasmic reticulum and may control cell death
      and regeneration within the central nervous system. Cutamesine (1-(3,4
      dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) is a ligand
      selective for this receptor and may mediate neuroprotective effects in the
      context of neurodegenerative disease. We therefore assessed whether cutamesine
      protects the inner ear from noise-induced or aging-associated hearing loss.
      Immunohistochemistry and Western blotting revealed that the sigma-1 receptor is
      present in adult cochlea. We treated mice with 0, 3, or 30 mg/kg cutamesine from
      10 days before noise exposure until the end of the study. All subjects were
      exposed to a 120-dB, 4-kHz octave-band noise for 2 hr. We assessed auditory
      thresholds by measuring the auditory-evoked brainstem responses at 4, 8, and 16
      kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the
      aging study, measurements were made before treatment was initiated and after 3 or
      9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral
      limbus was assessed by quantitative histology. Cutamesine significantly reduced
      threshold shifts and cell death within the spiral limbus in response to intense
      noise. These effects were not dose or time dependent. Conversely, cutamesine did
      not prevent aging-associated hearing loss. These results suggest that cutamesine
      reduces noise-induced hearing loss and cochlear damage during the acute phase
      that follows exposure to an intense noise.

PMID- 25612543
TI  - Effect of ultraviolet photofunctionalisation on the cell attractiveness of
      zirconia implant materials.
AB  - Ultraviolet (UV) light treatment of implant surfaces has been demonstrated to
      enhance their bioactivity significantly. This study examined the effect of UV
      treatment of different zirconia surfaces on the response of primary human
      alveolar bone-derived osteoblasts (PhABO). Disks of two zirconia-based materials
      with two different surface topographies (smooth, roughened) were exposed to UV
      light. Qualitative and quantitative assessment of PhABO on zirconia surfaces, by
      means of immunofluorescence, scanning electron microscopy and DNA quantification
      at 4 and 24 h revealed a higher number of initially attached osteoblasts on UV
      treated surfaces. Cell area and perimeter were significantly larger on all UV
      treated surfaces (p<0.05). The proliferation activity was significantly higher on
      both roughened UV-treated surfaces than on untreated samples at day 3 of culture
      (p<0.05). The expression levels of collagen I, osteopontin and osteocalcin at day
      14 and alkaline phosphatase activity at day 7 and 14 of culture period were
      similar among UV-treated and untreated surfaces. Alizarin-Red-Staining at day 21
      demonstrated significantly more mineralised nodules on UV-treated samples than on
      untreated samples. Contact angle measurements and X-ray photoelectron
      spectroscopy showed that UV light transformed zirconia surfaces from hydrophobic
      to (super-) hydrophilic (p<0.05) and significantly reduced the atomic percentage
      of surface carbon. The results showed that UV light pre-treatment of zirconia
      surfaces changes their physicochemical properties and improves their
      attractiveness against PhABO, primarily demonstrated by an augmented cell
      attachment and spreading. This may result in faster healing and better bone-to
      implant contact of zirconia implants in vivo following such a pre-treatment.

PMID- 25612542
TI  - Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors
      in microglia.
AB  - Selective elimination of synaptic connections is a common phenomenon which occurs
      during both developmental and pathological conditions. Glial cells have a central
      role in the pruning of synapses by specifically engulfing the degenerating
      neurites of inappropriate connections, but its regulatory mechanisms have been
      largely unknown. To identify mediators of this process, we established an in
      vitro cell culture assay for the synapse elimination. Neuronal differentiation
      and synapse formation of PC12 cells were induced by culturing the cells with
      nerve growth factor (NGF) in a serum-free medium. To trigger synapse elimination,
      the NGF-containing medium was replaced with DMEM containing 10% FBS, and the
      neurites of PC12 cells degenerated within two days. Co-culturing with MG6 cells,
      a mouse microglial cell line, accelerated the removal of degenerating neurites of
      PC12 cells by phagocytosis. When MG6 cells were pre-incubated with exosomes
      secreted from the differentiated PC12 cells after depolarization, the removal was
      further accelerated by increasing the expression levels of complement component 3
      in the MG6 cells. These results define a role for exosomes as a regulator of
      synapse elimination and clarify a novel mechanism whereby active synapses promote
      the pruning of inactive ones by stimulating microglial phagocytosis with
      exosomes. 

PMID- 25612544
TI  - Highly chromium contaminant tolerant BaO infiltrated La0.6Sr0.4Co0.2Fe0.8O3-delta
      cathodes for solid oxide fuel cells.
AB  - A BaO infiltrated La0.6Sr0.4Co0.2Fe0.8O3-delta (LSCF) cathode shows remarkable
      tolerance and resistance towards chromium via the formation of BaCrO4 instead of
      SrCrO4 on the electrode surface, preventing the excess Sr deficiency at the A
      site of LSCF perovskite and thus mitigating the Cr poisoning effect. 

PMID- 25612545
TI  - Targeting educational campaigns for prevention of malaria and dengue fever: an
      assessment in Thailand.
AB  - BACKGROUND: The current study assessed the knowledge, attitudes, and practices
      (KAP) of at-risk populations for malaria and/or dengue fever in relation to
      mosquito exposure and household mosquito control practices. Specific objectives
      included comparison of individual and household level health practices between a
      rural and urban setting in Thailand. Findings are intended to guide Thailand
      Ministry of Health educational campaigns targeting arthropod-borne disease.
      METHODS: A mixed method design was employed using a forced choice and open-ended
      questionnaire to assess KAP of participants seeking point-of-care treatment for
      malaria and/or dengue fever at government health-care facilities. Following
      informed consent, household construction characterization (percent eave gap,
      floor, wall, and roof material) and mosquito collections both indoors (using
      aspiration) and outside (using traps) were conducted at a subsample of
      participant homes. All mosquitoes were identified to genus and anopheline and
      aedine samples processed for potential pathogen infection. RESULTS: A total of 64
      participants were recruited from both study sites; 62 categorized as malaria
      symptomology and 2 categorized as dengue across all study healthcare facilities.
      Significant associations between study site and household construction were
      indicated. Trends also identified household level practices and both occupation
      and household construction regarding type of mosquito control products purchased
      and the abundance of mosquitoes in sampled homes. CONCLUSION: Overall, Ministry
      of Health information from education campaigns regarding malaria and dengue fever
      strategies is reaching the intended target populations at the study sites.
      Participants are aware of the presence of mosquitoes and that they serve as the
      potential vector for transmitting malaria and dengue fever diseases. However,
      specific knowledge gaps were also identified in each study site that may
      influence exposure to infected mosquitoes. Findings from this study are intended
      to guide future health education campaigns in these study settings to address
      specific community needs.

PMID- 25612546
TI  - Serum Abeta is predictive for short-term neurological deficits after acute
      ischemic stroke.
AB  - Mounting evidence suggests that ischemic stroke (IS) is associated with
      Alzheimer's disease (AD). IS and vascular risk factors increase the risk for AD.
      However, whether AD pathologies exist in IS and the effects of these pathologies
      on stroke remain unknown. In the present study, we aimed to investigate the
      alterations of serum Abeta after acute IS (AIS), and its correlations with the
      neurological deficits, infarction volume, and site after stroke. AIS patients (n
      = 35) were recruited within 24 h of symptom onset. Age- and gender-matched AD
      patients (n = 48) and cognitively normal controls (NC, n = 37) were also
      enrolled. Serum Abeta40 and Abeta42 and the National Institute of Health Stroke
      Scale Score (NIHSS) were measured on day 1, 3, and 7 after stroke onset. We found
      that serum Abeta40 and Abeta42 levels were increased at day 1 and reached peak
      levels at day 3, and decreased to pre-stroke levels at day 7. Serum Abeta40
      levels at day 1 were correlated with the NIHSS scores and infarction volume of
      AIS patients. Serum Abeta42 levels at day 1 were significantly higher in IS
      patients with dominant gray matter infarction. Serum Abeta40 levels at day 1 were
      predictive for NIHSS at day 7. Our results indicate that AIS can induce the
      generation of Abeta in the brain, which may in turn be involved in the
      pathogenesis of neurological deficits after stroke. Serum Abeta might be
      predictive for the short-term neurological deficits after AIS.

PMID- 25612547
TI  - No difference in incidence of port-site hernia and chronic pain after single
      incision laparoscopic cholecystectomy versus conventional laparoscopic
      cholecystectomy: a nationwide prospective, matched cohort study.
AB  - BACKGROUND: Conventional laparoscopic cholecystectomy (CLC) is regarded as the
      gold standard for cholecystectomy. However, single-incision laparoscopic
      cholecystectomy (SLC) has been suggested to replace CLC. This study aimed at
      comparing long-term incidences of port-site hernia and chronic pain after SLC
      versus CLC. METHODS: We conducted a matched cohort study based on prospective
      data (Jan 1, 2009-June 1, 2011) from the Danish Cholecystectomy Database with
      perioperative information and clinical follow-up. Consecutive patients undergoing
      elective SLC during the study period were included and matched 1:2 with patients
      subjected to CLC using pre-defined criteria. Follow-up data were obtained from
      the Danish National Patient Registry, mailed patient questionnaires, and clinical
      examination. A port-site hernia was defined as a repair for a port-site hernia or
      clinical hernia located at one or more port sites. RESULTS: In total, 699
      patients were eligible and 147 patients were excluded from the analysis due to
      pre-defined criteria. The rate of returned questionnaires was 83%. Thus, 552
      (SLC, n = 185; CLC, n = 367) patients were analyzed. The median observation time
      was 48 months (range 1-65) after SLC and 48 months (1-64) after CLC (P = 0.940).
      The total cumulated port-site hernia rate was 4 % and 6 % for SLC and CLC,
      respectively (P = 0.560). Incidences of moderate/severe chronic pain were 4 % and
      5 % after SLC and CLC, respectively (P = 0.661). CONCLUSIONS: We found no
      difference in long-term incidence of port-site hernia or chronic pain after SLC
      versus CLC.

PMID- 25612548
TI  - Surgery duration predicts urinary retention after inguinal herniorrhaphy: a
      single institution review.
AB  - BACKGROUND: Inguinal hernia repair, laparoscopic or open, is one of the most
      frequently performed operations in general surgery. Postoperative urinary
      retention (POUR) can occur in 0.2-35 % of patients after inguinal hernia repair.
      The primary objective of this study was to determine the incidence of POUR after
      inguinal hernia repair. As a secondary goal, we sought to determine whether
      perioperative and patient factors predicted urinary retention. METHODS: This
      study is a retrospective review of patients who underwent inguinal hernia repair
      with synthetic mesh at the Medical College of Wisconsin from January 2007 to June
      2012. Procedures were performed by four surgeons. Clinical information and
      perioperative outcomes were collected up to hospital discharge. Urinary retention
      was defined as need for urinary catheterization postoperatively. RESULTS: A total
      of 192 patients were included in the study (88 bilateral, 46 %) and (104
      unilateral, 54 %). The majority of subjects (76 %) underwent laparoscopic repair.
      The overall POUR rate was 13 %, with 25 of 192 patients requiring a Foley
      catheter prior to discharge. POUR was significantly associated with bilateral
      hernia repairs (p = 0.04), BMI >= 35 kg/m(2) (p = 0.05) and longer operative
      times (p = 0.03). Based on odds ratio (OR) estimates, for every 10-min increase
      in operative time, an 11 % increase in the odds of urinary retention is expected
      (OR 1.11, CI 1.004-1.223; p = 0.04). For every 10-min increase in operative time,
      an 11 % increase in POUR is expected. CONCLUSIONS: Bilateral hernia repairs, BMI
      >= 35 kg/m(2), and operative time are significant predictors of POUR. These
      factors are important to determine potential risk to patients and interventions
      such as strict fluid administration, use of catheters, and potential
      premedication.

PMID- 25612550
TI  - Time trends in serum organochlorine pesticides and polychlorinated biphenyls in
      the general population of Biscay, Spain.
AB  - Despite the measures adopted, levels of organochlorine compounds (OCs) are still
      being detected in the human body. This study aimed to explore factors related to
      changes in the concentrations of polychlorinated biphenyls (PCBs) and pesticide
      OCs in blood samples obtained from a general population cohort. Two cross
      sectional samples were taken from 162 adults (2-75 years of age), with a gap of 2
      years, from four areas in Biscay (Spain). More than 75 % had quantifiable levels
      of hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH),
      dichlorodiphenyldichloroethylene, and PCBs 138 153 and 180. During this time,
      significant changes were observed: PCB 180 and HCB levels increased, and PCB 138
      and beta-HCH levels decreased. Regarding age, this study shows a decrease
      suggesting a cohort effect. The period was not related to the decrease of levels
      in all age intervals, but a statistically significant increase of PCBs in older
      people was found. High body mass index was associated with lower PCB 180 levels
      and greater HCH levels. Inversely, greater levels of HCB and beta-HCH were in
      those who had lost weight before the study. Levels of HCB and beta-HCH were also
      greater in women who had had children, although they were lower in those who
      breastfed. Levels of these same OCs were greater in fish consumers, whereas those
      of PCBs 138 and 153 were greater in those who consumed local produce; all of
      these trends were close to significance. Efforts should continue to decrease
      exposure to these pollutants and to assess their influence on general population.

PMID- 25612549
TI  - miRNA expression in human intestinal Caco-2 cells is comparably regulated by cis-
      and trans-fatty acids.
AB  - Trans-fatty acids are unsaturated fatty acids with at least one double bond in
      trans configuration. While their role in the development of coronary heart
      disease is broadly accepted, a potential impact of these fatty acids on colon
      carcinogenesis is still under discussion. MiRNAs are small non-coding RNAs that
      regulate the gene expression at a post-transcriptional level by inhibiting the
      translation of target mRNAs. We investigated the effect of 16 different C 18
      fatty acid isomers on the expression of 84 cancer-related miRNAs in the human
      colorectal adenocarcinoma cell line Caco-2 by using a qRT-PCR array. 66 of these
      84 miRNAs were deregulated by at least one fatty acid, however, there was no
      trans-specific impact on miRNA expression as the corresponding cis isomer of a
      given fatty acid generally had comparable effects on the miRNA expression
      profile. The most pronounced effects were observed for hsa-miR-146a-5p, which was
      upregulated by four of the 16 investigated fatty acids, and hsa-miR-32-5p, which
      was strongly downregulated by five fatty acids. As hsa-miR-32-5p was described to
      target genes being involved in the regulation of apoptosis, the effect of alpha
      eleostearic acid on the expression of the apoptosis-associated genes BCL2L11, BCL
      2, and BCL-XL was examined. The qPCR results indicate that fatty acid-mediated
      downregulation of hsa-miR-32-5p is accompanied by a downregulation of BCL-2 and
      BCL2L11 mRNA whereas BCL-XL was shown to be simultaneously upregulated. In
      conclusion, our data indicate that several fatty acids are able to regulate miRNA
      expression of human colon cancer cells. However, no trans-specific regulation was
      observed. 

PMID- 25612551
TI  - Tributyltin chloride (TBTCl)-enhanced exopolysaccharide and siderophore
      production in an estuarine Alcaligenes faecalis strain.
AB  - Tributyltin chloride (TBTCl) has been used extensively as an antifouling agent in
      ship paints, which results in the contamination of aquatic sites. These
      contaminated sites serve as enrichment areas for TBTCl-resistant bacterial
      strains. One TBTCl-resistant bacterial strain was isolated from the sediments of
      Zuari estuary, Goa, India, which is a major hub of various ship-building
      activities. Based on biochemical characteristics and 16S rDNA sequence analysis,
      this bacterial strain was identified as Alcaligenes faecalis and designated as
      strain SD5. It could degrade >=3 mM TBTCl by using it as a sole carbon source and
      transform it into the less toxic dibutyltin chloride, which was confirmed by
      nuclear magnetic resonance and mass spectroscopy. Interestingly, this bacterial
      strain also showed enhanced exopolysaccharide and siderophore production when
      cells were exposed to toxic levels of TBTCl, suggesting their involvement in
      conferring resistance to this antifouling biocide as well as degradative
      capability respectively. 

PMID- 25612554
TI  - Electron-boson spectral density of LiFeAs obtained from optical data.
AB  - We analyze existing optical data in the superconducting state of LiFeAs at T = 4
      K, to recover its electron-boson spectral density. A maximum entropy technique is
      employed to extract the spectral density I(2)chi(omega) from the optical
      scattering rate. Care is taken to properly account for elastic impurity
      scattering which can importantly affect the optics in an s-wave superconductor,
      but does not eliminate the boson structure. We find a robust peak in
      I(2)chi(omega) centered about Omega(R) ? 8.0 meV or 5.3 k(B)Tc (with Tc = 17.6
      K). Its position in energy agrees well with a similar structure seen in scanning
      tunneling spectroscopy (STS). There is also a peak in the inelastic neutron
      scattering (INS) data at this same energy. This peak is found to persist in the
      normal state at T = 23 K. There is evidence that the superconducting gap is
      anisotropic as was also found in low temperature angular resolved photoemission
      (ARPES) data.

PMID- 25612552
TI  - Abeta induces oxidative stress in senescence-accelerated (SAMP8) mice.
AB  - According to the amyloid hypothesis, amyloid beta accumulates in brains with
      Alzheimer's disease (AD) and triggers cell death and memory deficit. Previously,
      we developed a rice Abeta vaccine expressing Abeta, which reduced brain Abeta
      levels in the Tg2576 mouse model of familial AD. We used senescence-accelerated
      SAMP8 mice as a model of sporadic AD and investigated the relationship between
      Abeta and oxidative stress. Insoluble Abeta and 4-hydroxynonenal (4-HNE) levels
      tended to be reduced in SAMP8 mice-fed the rice Abeta vaccine. We attempted to
      clarify the relationship between oxidative stress and Abeta in vitro. Addition of
      Abeta peptide to the culture medium resulted in an increase in 4-HNE levels in SH
      SY5Y cells. Tg2576 mice, which express large amounts of Abeta in their brain,
      also exhibited increased 4-HNE levels; this increase was inhibited by the Abeta
      vaccine. These results indicate that Abeta induces oxidative stress in cultured
      cells and in the mouse brain. 

PMID- 25612555
TI  - The utility of multiparametric seven-color flow cytometry in the detection of
      double hit lymphoma in ascitic fluid samples.
AB  - Double-hit lymphoma (DHL) is a rare type of lymphoma with concurrent chromosomal
      translocations of C-MYC with BCL2 or BCL6, associated with unfavorable prognosis.
      We describe a case of DHL in a 79-year-old female patient previously diagnosed
      with diffuse large B-cell lymphoma (DLBCL) with an early relapse in the ascitic
      fluid. A seven-color multiparametric flow cytometry immunophenotyping study of
      the ascitic fluid was carried out, and revealed 99.78% of large in size and high
      cellular complexity B-cells positive for CD19, CD10 (64.27%), CD45 dim, CD22 dim,
      CD25 (60%), CD43 bright, CD38 bright, and IgM (18.53%); and negative for CD20,
      CD5, CD23, CD79b, CD103, CD200, CD11c, and FMC7, and 78.99% without light chain
      expression and 21% with Lambda chain restriction. Due to the expression of CD19
      and CD10 with overexpression of BCL-2 protein and due to CD43 and CD38 positivity
      detected, those cells showed features between DLBCL and Burkitt lymphoma.
      Fluorescence in situ hybridization (FISH) confirmed both c-MYC/IGH and BCL2/IGH
      rearrangement. Our findings may help to identify cases requiring additional
      cytogenetic analysis. (c) 2015 International Clinical Cytometry Society.

PMID- 25612556
TI  - Effects of feeding high protein or conventional canola meal on dry cured and
      conventionally cured bacon.
AB  - Objectives were to compare belly, bacon processing, bacon slice, and sensory
      characteristics from pigs fed high protein canola meal (CM-HP) or conventional
      canola meal (CM-CV). Soybean meal was replaced with 0 (control), 33, 66, or 100%
      of both types of canola meal. Left side bellies from 70 carcasses were randomly
      assigned to conventional or dry cure treatment and matching right side bellies
      were assigned the opposite treatment. Secondary objectives were to test the
      existence of bilateral symmetry on fresh belly characteristics and fatty acid
      profiles of right and left side bellies originating from the same carcass.
      Bellies from pigs fed CM-HP were slightly lighter and thinner than bellies from
      pigs fed CM-CV, yet bacon processing, bacon slice, and sensory characteristics
      were unaffected by dietary treatment and did not differ from the control.
      Furthermore, testing the existence of bilateral symmetry on fresh belly
      characteristics revealed that bellies originating from the right side of the
      carcasses were slightly (P<=0.05) wider, thicker, heavier and firmer than bellies
      from the left side of the carcass. 

PMID- 25612557
TI  - Risk-based control of food-borne pathogens Listeria monocytogenes and Salmonella
      enterica in the Italian fermented sausages Cacciatore and Felino.
AB  - Fermentation is the most important killing step during production of fermented
      meats to eliminate food-borne pathogens. The objective was to evaluate whether
      the food-borne pathogens Listeria monocytogenes and Salmonella enterica may
      survive during the production of two Italian fermented sausages. Sausage batter
      was inoculated with five strains of L. monocytogenes or S. enterica (ca. 10(5)
      10(6) cfu/g) and their kinetic behavior was monitored during production. Both
      pathogens survived relatively well (in Cacciatore L. monocytogenes and S.
      enterica inactivation was ca. 0.38+/-0.23 and 1.10+/-0.24 log cfu/g,
      respectively; in Felino was ca. 0.39+/-0.25 and 1.62+/-0.38 log cfu/g,
      respectively) due to the conditions prevailing during production (slow
      dehydration rate, small reduction of water activity and fermentation temperature
      mainly below 20  degrees C during the first 48 h of fermentation). Quantitative
      analysis of data originating from challenge tests provide critical information on
      which combinations of the process parameters would potentially lead to better
      control of the pathogens.

PMID- 25612558
TI  - Role of L-alanine for redox self-sufficient amination of alcohols.
AB  - BACKGROUND: In white biotechnology biocatalysis represents a key technology for
      chemical functionalization of non-natural compounds. The plasmid-born
      overproduction of an alcohol dehydrogenase, an L-alanine-dependent transaminase
      and an alanine dehydrogenase allows for redox self-sufficient amination of
      alcohols in whole cell biotransformation. Here, conditions to optimize the whole
      cell biocatalyst presented in (Bioorg Med Chem 22:5578-5585, 2014), and the role
      of L-alanine for efficient amine functionalization of 1,10-decanediol to 1,10
      diaminodecane were analyzed. RESULTS: The enzymes of the cascade for amine
      functionalization of alcohols were characterized in vitro to find optimal
      conditions for an efficient process. Transaminase from Chromobacterium violaceum,
      TaCv, showed three-fold higher catalytic efficiency than transaminase from Vibrio
      fluvialis, TaVf, and improved production at 37 degrees C. At 42 degrees C, TaCv
      was more active, which matched thermostable alcohol dehydrogenase and alanine
      dehydrogenase and improved the 1,10-diaminodecane production rate four-fold. To
      study the role of L-alanine in the whole cell biotransformation, the L-alanine
      concentration was varied and 1,10.diaminodecane formation tested with constant 10
      mM 1,10- decanediol and 100 mM NH4Cl. Only 5.6% diamine product were observed
      without added L-alanine. L-alanine concentrations equimolar to that of the
      alcohol enabled for 94% product formation but higher L-alanine concentrations
      allowed for 100% product formation. L-alanine was consumed by the E. coli
      biocatalyst, presumably due to pyruvate catabolism since up to 16 mM acetate
      accumulated. Biotransformation employing E. coli strain YYC202/pTrc99a-ald-adh-ta
      Cv, which is unable to catabolize pyruvate, resulted in conversion with a
      selectivity of 42 mol-%. Biotransformation with E. coli strains only lacking
      pyruvate oxidase PoxB showed similar reduced amination of 1,10-decanediol
      indicating that oxidative decarboxylation of pyruvate to acetate by PoxB is
      primarily responsible for pyruvate catabolism during redox self-sufficient
      amination of alcohols using this whole cell biocatalyst. CONCLUSION: The
      replacement of the transaminase TaVf by TaCv, which showed higher activity at 42
      degrees C, in the artificial operon ald-adh-ta improved amination of alcohols in
      whole cell biotransformation. The addition of L-alanine, which was consumed by E.
      coli via pyruvate catabolism, was required for 100% product formation possibly by
      providing maintenance energy. Metabolic engineering revealed that pyruvate
      catabolism occurred primarily via oxidative decarboxylation to acetate by PoxB
      under the chosen biotranformation conditions.

PMID- 25612559
TI  - Does the nature of residual immune function explain the differential risk of non
      melanoma skin cancer development in immunosuppressed organ transplant recipients?
AB  - Patients receiving immunosuppression to prevent organ transplant rejection are at
      a greatly increased risk of developing nonmelanoma skin cancer. In recent years a
      correlation has been identified between the class of immunosuppressant that these
      patients receive and their subsequent cancer risk; in particular, patients
      switched from calcineurin inhibitors to mammalian target of rapamycin (mTOR)
      inhibitors not only displayed a dramatic reduction in new tumor formation but
      also in some cases a regression of their existing lesions. Studies of cancer
      models in mice and cell lines in the laboratory have attributed these
      discrepancies in cancer risk to the ability of immunosuppressants such as mTOR
      inhibitors to elicit direct anticancer effects, including suppressing
      angiogenesis and increasing autophagy-mediated DNA repair. Recent evidence from
      the immunological literature however, suggests a significant alternative
      contribution of mTOR inhibitors; namely the promotion of memory T-cell function.
      Recent advances in understanding memory T-cell establishment and the
      demonstration of their critical role in long-term immunity make it timely to
      review the available evidence as to whether the improved nonmelanoma skin cancer
      outcome shown by patients switched to mTOR inhibitor treatment regimens may be
      associated with the retainment of memory T-cell function. 

PMID- 25612560
TI  - A convenient route to tetraalkylammonium perfluoroalkoxides from
      hydrofluoroethers.
AB  - Hydrofluoroethers are shown to alkylate tertiary amines readily under solvent
      free conditions, affording valuable tetraalkylammonium perfluoroalkoxides bearing
      alpha-fluorines. The reaction of R(F)CF2-OCH3 (R(F)=CF2CF3, CF2CF2CF3, and
      CF(CF3)2) with NR(1)R(2)R(3) produces twenty new alpha-perfluoroalkoxides,
      [(CH3)NR(1)R(2)R(3)][R(F)CF2O] under mild conditions. These alpha
      perfluoroalkoxides are easy to handle, thermally stable, and can be used for the
      perfluoroalkoxylation of benzyl bromides.

PMID- 25612561
TI  - 20th International Chromosome Conference (ICCXX) : 50th Anniversary, University
      of Kent, Canterbury, 1st-4th September 2014.

PMID- 25612562
TI  - New cryptic karyotypic differences between cattle (Bos taurus) and goat (Capra
      hircus).
AB  - Cattle (Bos taurus) and goat (Capra hircus) belong to the Bovidae family, and
      they share a common ancestor 19.7-21.5 Ma ago (MYA). The Bovidae family
      apparently experienced a rapid species radiation in the middle Miocene. The
      present day cattle and goat possess the same diploid chromosome number (2n = 60)
      and structurally similar autosomes, except that a small subcentromeric portion of
      cattle chromosome nine has been translocated to goat chromosome 14. In this
      study, we adopted a new strategy that involves the use of bioinformatics approach
      to detect unknown cryptic chromosome divergences between cattle and goat using
      and subsequent validation using the fluorescence in situ hybridization (FISH) of
      bacterial artificial chromosome clones. We identified two hypothetical
      discrepancies between the cattle and goat genome assemblies: an inversion in the
      goat chromosome 13 and a transposition in the goat chromosome 6. The FISH
      technique allowed clear validation of the existence of a new 7.4 Mb chromosomal
      inversion in the goat chromosome 13. Regarding the transposition in the goat
      chromosome six, FISH analyses revealed that the cattle and goat genomes shared
      the same organization, with the assembly of the goat genome being the correct
      one. Moreover, we defined, for the first time, the size and orientation of the
      translocated fragment involved in the evolutionary translocation between cattle
      chromosomes 9 and goat chromosome 14. Our results suggest that bioinformatics
      represents an efficient method for detecting cryptic chromosome divergences among
      species. 

PMID- 25612564
TI  - Simultaneous determination of albumin and low-molecular-mass thiols in plasma by
      HPLC with UV detection.
AB  - In this paper, we describe a simple and robust HPLC based method for
      determination of total low- and high-molecular-mass thiols, protein S-linked
      thiols and reduced albumin in plasma. The method is based on derivatization of
      analytes with 2-chloro-1-methylquinolinium tetrafluoroborate, separation and
      quantification by reversed-phase liquid chromatography followed by UV detection.
      Disulfides were converted to their thiol counterparts by reductive cleavage with
      tris(2-carboxyethyl)phosphine. Linearity in detector response for total thiols
      was observed over the range of 1-40 MUmol L(-1) for Hcy and glutathione (GSH), 5
      100 MUmol L(-1) for Cys-Gly, 20-300 MUmol L(-1) for Cys and 3.1-37.5 MUmol L(-1)
      (0.2-2.4gL(-1)) for human serum albumin (HSA). For the protein S-bound forms
      these values were as follows: 0.5-30 MUmol L(-1) for Hcy and GSH, 2.5-60 MUmol L(
      1) for Cys-Gly and 5-200 MUmol L(-1) for Cys. The LOQs for total HSA, Cys, Hcy,
      Cys-Gly and GSH were 0.5, 0.2, 0.4, 0.3 and 0.4 MUmol L(-1), respectively. The
      estimated validation parameters for all analytes are more than sufficient to
      allow the analytical method to be used for monitoring of the total and protein
      bound thiols as well as redox status of HSA in plasma.

PMID- 25612563
TI  - Characterization and reactivity of a terminal nickel(III)-oxygen adduct.
AB  - High-valent terminal metal-oxygen adducts are hypothesized to be the potent
      oxidizing reactants in late transition metal oxidation catalysis. In particular,
      examples of high-valent terminal nickel-oxygen adducts are scarce, meaning there
      is a dearth in the understanding of such oxidants. A monoanionic Ni(II)
      bicarbonate complex has been found to react in a 1:1 ratio with the one-electron
      oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally
      unstable intermediate in high yield (ca. 95%). Electronic absorption, electronic
      paramagnetic resonance, and X-ray absorption spectroscopies and density
      functional theory calculations confirm its description as a low-spin (S = 1/2),
      square planar Ni(III)-oxygen adduct. This rare example of a high-valent terminal
      nickel-oxygen complex performs oxidations of organic substrates, including 2,6-di
      tert-butylphenol and triphenylphosphine, which are indicative of hydrogen atom
      abstraction and oxygen atom transfer reactivity, respectively.

PMID- 25612565
TI  - Hemorrhoidopexy with the HemorPex system.

PMID- 25612566
TI  - Infliximab drug and antibody levels in patients with dermatological conditions.
AB  - BACKGROUND: In recent years, studies monitoring infliximab in rheumatoid
      arthritis and inflammatory bowel disease have confirmed the relationship between
      the clinical response and the infliximab and anti-infliximab antibodies serum
      levels. However, there is only limited evidence in the field of dermatology.
      OBJECTIVE: The aim of this study was to establish the correlation between plasma
      infliximab levels, the presence of anti-infliximab antibodies and the clinical
      response in dermatological conditions. SETTING: Retrospective observational study
      in a tertiary hospital (University Hospital of La Coruna, Spain). METHOD:
      Patients with dermatological conditions being treated with infliximab (5 mg/kg/8
      weeks after the induction dose) were included in the study. The concentrations of
      infliximab and anti-infliximab antibodies were quantified by two sandwich-type
      ELISA immunoassays. The patients were classified into three groups based on the
      efficacy: good, partial or non-efficacy at the time of each blood assessment. The
      development of adverse reactions was also evaluated. MAIN OUTCOME MEASURES:
      Plasma levels of infliximab and anti-infliximab antibodies, clinical response and
      infusion reactions. RESULTS: 17 patients (45 assessments) were included. The
      good/partial efficacy rate was significantly higher in the case of >0.05 than
      <0.05 MUg/mL infliximab concentration (93.3 vs. 40.0 %, p < 0.001). Anti
      infliximab antibodies were only detected in five samples. Their presence was
      associated with a higher frequency of infusion reactions and a lower efficacy
      rate in comparison with the group without antiinfliximab antibodies (100.0 vs.
      0.0 %, p < 0.001 and 0.0 vs. 85.0 %, p < 0.001 respectively). CONCLUSIONS: The
      results obtained show that the presence of infliximab concentrations higher than
      0.05 MUg/mL are correlated with a good clinical response and the absence of
      toxicity. The incidence of anti-infliximab antibodies is low, although a
      correlation was observed between the presence of antibodies, absence of
      infliximab concentration, loss of clinical response and the development of
      infusion reactions.

PMID- 25612567
TI  - Secondary acute myeloid leukemia arising early after cyclophosphamide treatment.
AB  - BACKGROUND: Acute myeloid leukemia (AML) can develop secondary to drug treatment.
      This phenomenon has been placed under the title "Therapy Related Acute Myeloid
      Leukemias and Myelodysplastic Syndromes" in the WHO classification of AML.
      Cyclophosphamide, which is used in various malignancies and rheumatological
      diseases, is an alkylating agent that plays a significant role in therapy related
      AML. CASE DESCRIPTION: A patient treated with cyclophosphamide due to vasculitis,
      subsequently developed AML months after treatment. CONCLUSION: Cyclophosphamide
      related AML is seen, in most cases, many years after exposure to the drug. The
      significance of this report lies in the fact that, to our knowledge, this is the
      most rapidly arising case of cyclophosphamide related AML.

PMID- 25612570
TI  - Sleeping on stomach is associated with sudden death in epilepsy, study finds.

PMID- 25612568
TI  - Elite athletes' genetic predisposition for altered risk of complex metabolic
      traits.
AB  - BACKGROUND: Genetic variants may predispose humans to elevated risk of common
      metabolic morbidities such as obesity and Type 2 Diabetes (T2D). Some of these
      variants have also been shown to influence elite athletic performance and the
      response to exercise training. We compared the genotype distribution of five
      genetic Single Nucleotide Polymorphisms (SNPs) known to be associated with
      obesity and obesity co-morbidities (IGF2BP2 rs4402960, LPL rs320, LPL rs328, KCJN
      rs5219, and MTHFR rs1801133) between athletes (all male, n = 461; endurance
      athletes n = 254, sprint/power athletes n = 207), and controls (all male, n =
      544) in Polish and Russian samples. We also examined the association between
      these SNPs and the athletes' competition level ('elite' and 'national' level).
      Genotypes were analysed by Single-Base Extension and Real-Time PCR. Multinomial
      logistic regression analyses were conducted to assess the association between
      genotypes and athletic status/competition level. RESULTS: IGF2BP2 rs4402960 and
      LPL rs320 were significantly associated with athletic status; sprint/power
      athletes were twice more likely to have the IGF2BP2 rs4402960 risk (T) allele
      compared to endurance athletes (OR = 2.11, 95% CI = 1.03-4.30, P <0.041), and non
      athletic controls were significantly less likely to have the T allele compared to
      sprint/power athletes (OR = 0.62, 95% CI =0.43-0.89, P <0.0009). The control
      group was significantly more likely to have the LPL rs320 risk (G) allele
      compared to endurance athletes (OR = 1.26, 95% CI = 1.05-1.52, P <0.013). Hence,
      endurance athletes were the "protected" group being significantly (p < 0.05) less
      likely to have the risk allele compared to sprint/power athletes (IGF2BP2
      rs4402960) and significantly (p < 0.05) less likely to have the risk allele
      compared to controls (LPL rs320). The other 3 SNPs did not show significant
      differences between the study groups. CONCLUSIONS: Male endurance athletes are
      less likely to have the metabolic risk alleles of IGF2BP2 rs4402960 and LPL
      rs320, compared to sprint/power athletes and controls, respectively. These
      results suggest that some SNPs across the human genome have a dual effect and may
      predispose endurance athletes to reduced risk of developing metabolic
      morbidities, whereas sprint/power athletes might be predisposed to elevated risk.

PMID- 25612571
TI  - Common polymorphisms in WNT10A affect tooth morphology as well as hair shape.
AB  - Hair and teeth are appendages of ectodermal origin, and there are common
      molecular backgrounds involved in their formation. To date, it has been revealed
      that a non-synonymous polymorphism in EDAR has effects on the morphological
      variation in both hair and teeth. Previous association studies have confirmed
      that single-nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1
      and FGFR2 are associated with hair morphology. In this study, we thus examined
      whether these SNPs are also associated with dental characteristics. We measured
      metric dental traits including crown size and also evaluated non-metric dental
      traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans).
      DNA samples were prepared from the subjects and genotyped for the hair morphology
      associated SNPs. We observed a significant association of crown size with an SNP
      in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further
      examined four SNPs within and around WNT10A, among which rs10177996 had the
      strongest association with dental traits. World distribution of the derived
      allele in rs10177996, which is associated with larger teeth, showed that
      Eurasians have a higher allele frequency than Africans. Together with previous
      studies on hair morphology, this study demonstrated that common variations in
      WNT10A have pleiotropic effects on the morphology of ectodermal appendages. 

PMID- 25612572
TI  - The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy
      in PINK1/PARK2 pathway.
AB  - Mitochondrial dysfunction plays important roles in Parkinson's disease (PD) and
      the degradation of the damaged mitochondria by the mitochondria quality control
      system is important for dopaminergic (DA) neuronal survival. BNIP3L/Nix is a
      mitochondrial outer membrane protein that is required for the selective clearance
      of mitochondria. Here, we found that the mitochondrial protein BNIP3L acts
      downstream of the PINK1/PARK2 pathway to induce mitophagy. BNIP3L is a substrate
      of PARK2 to drive PARK2-mediated mitophagy. The ubiquitination of BNIP3L by PARK2
      recruits NBR1 to mitochondria, thereby targeting mitochondria for degradation.
      BNIP3L rescues mitochondrial defects in pink1 mutant Drosophila but not in park
      mutant Drosophila, indicating that the clearance of mitochondria induced by
      BNIP3L depends on the presence of PARK2. In cells intoxicated with mitochondrial
      complex I inhibitors rotenone, 6-OHDA or MPP(+), the disrupted mitochondria are
      not appropriately eliminated by mitophagy due to the improper degradation of
      BNIP3L. Thus, our study demonstrates that BNIP3L, as a substrate of PARK2,
      promotes mitophagy in the PINK1/PARK2 pathway associated with PD pathogenesis. 

PMID- 25612573
TI  - Re: "analyzing risks of adverse pregnancy outcomes".

PMID- 25612574
TI  - The authors reply.

PMID- 25612575
TI  - Pneumomediastinum as a complication of SABR for lung metastases.
AB  - BACKGROUND: Stereotactic ablative body radiation (SABR) is a novel and
      sophisticated radiation modality that involves the irradiation of extracranial
      tumors through precise and very high doses in patients with oligometastatic lung
      disease and primary lung tumors. CASE PRESENTATION: A 52-year-old female with
      subclinical idiopathic interstitial lung disease (ILD) and oligometastatic lung
      disease from squamous urethral cancer who was treated with SABR for a metastatic
      lesion located in the right lower pulmonary lobe. The patient received a hypo
      fractionated course of SABR. A 3D-conformal multifield technique was used with
      six coplanar and one non-coplanar statics beams. A 48 Gy total dose in three
      fractions over six days was prescribed to the 95% of the PTV. The presence of
      idiopathic ILD and other identifiable underlying lung conditions were not taken
      into account as a constraint to prescribe a different than standard total dose or
      fractionation schedule. Six months after the SABR treatment, a CT-scan showed the
      presence of a pneumomediastinum with air outside the bronchial tree and within
      the subcutaneous tissue without co-existing pneumothorax. To our knowledge, this
      is the first case of pneumomediastinum appearing 6 months after SABR treatment
      for a lung metastasis located in the perihiliar/central tumors region as defined
      by the RTOG protocols as the proximal bronchial tree. CONCLUSION: Radiation
      oncologist should be aware of the potential risk of severe lung toxicity caused
      by SABR in patients with ILD, especially when chemotherapy-induced pulmonary
      toxicity is administered in a short time interval.

PMID- 25612601
TI  - Children's and parents' health perception of different soft drinks.
AB  - Beverages are among the first independent product choices that school-aged
      children will make and unhealthy choices can be a threat to children's health.
      The present study investigated which beverage attributes shape adults' and
      children's health perceptions. For this purpose, 100 children (fifty-two boys;
      mean age 8.8 (SD 1.1) years) and their parents were invited to independently
      perform a beverage-sorting task. Participants were asked to place twenty commonly
      consumed soft drinks in a line ranging from 'unhealthy' to 'healthy'. The sorting
      data were analysed using multidimensional scaling with property fitting and
      hierarchical clustering. Sugar content (betaparents= - 0.78, betachildren= -
      0.68; P< 0.001), artificial sweeteners (betaparents= - 0.68, betachildren= -
      0.66; P< 0.001), fruit content (betaparents= 0.33, betachildren= 0.36; P< 0.05)
      and caffeine content (betaparents= - 0.45, betachildren= - 0.46; P< 0.01) were
      found to be the predictors of parents' and children's health perceptions.
      Parents' and children's estimates were strongly related (rs 0.70 (SD 0.15)); both
      groups classified the beverages into similar clusters. However, compared with
      their parents, children perceived beverages such as fruit juices and grapefruit
      soda to be healthier. In conclusion, parents' and children's health perceptions
      were strongly related based on the same relevant attributes for evaluation.
      However, fruit content was considered a more important criterion by children,
      which might lead to differences in the health perception between children and
      their parents. Low fruit content and the belief of beverages being 'natural'
      could positively bias perceptions. Therefore, certain soft drinks such as
      squashes or fruit lemonades are problematic, and the consumer's awareness of
      their low nutritional quality should be raised.

PMID- 25612602
TI  - A one-page summary report of genome sequencing for the healthy adult.
AB  - As genome sequencing technologies increasingly enter medical practice, genetics
      laboratories must communicate sequencing results effectively to nongeneticist
      physicians. We describe the design and delivery of a clinical genome sequencing
      report, including a one-page summary suitable for interpretation by primary care
      physicians. To illustrate our preliminary experience with this report, we
      summarize the genomic findings from 10 healthy participants in a study of genome
      sequencing in primary care.

PMID- 25612604
TI  - Two novel mutations in the gene that codes for acid alpha-glucosidase in a baby
      with Pompe disease.

PMID- 25612603
TI  - Low-dose RATG with or without basiliximab in renal transplantation: a matched
      cohort observational study.
AB  - BACKGROUND/AIMS: In renal transplantation, peri-operative low-dose rabbit
      antithymocyte-globulin (RATG) plus basiliximab induction prevented acute
      allograft rejection more effectively than post-operative RATG plus basiliximab
      induction. We investigated the specific antirejection contribution of basiliximab
      in this context. METHODS: This single-center, observational, matched-cohort study
      evaluated allograft rejections (primary outcome), steroid exposure and side
      effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor
      renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender
      and treatment-matched reference-patients given RATG plus basiliximab (20 mg on
      days 0 and 4). RESULTS: Induction was well tolerated. At 18 months, 8 patients
      (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73
      24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting
      for recipient/donor age and gender, cold ischemia time and HLA mismatches. There
      were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients
      vs. none in reference-patients (p = 0.032). The median (interquartile range)
      prednisone cumulative dose was remarkably higher in patients than reference
      patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients
      vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three
      patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both
      inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated
      participants were similar. GFR was similar in all groups. Compared to MMF, AZA
      therapy saved ~ EUR 2,500/year and by month 14.3 post-transplant compensated
      basiliximab costs. CONCLUSION: In renal transplantation, basiliximab plus peri
      operative low-dose RATG more efficiently prevented allograft rejection than RATG
      monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based
      maintenance immunosuppression largely compensated the extra costs of basiliximab.

PMID- 25612606
TI  - Heme oxygenase-1 restores impaired GARPCD4+CD25+ regulatory T cells from patients
      with acute coronary syndrome by upregulating LAP and GARP expression on activated
      T lymphocytes.
AB  - BACKGROUND: Accumulating evidence shows that the pathological autoreactive immune
      response is responsible for plaque rupture and the subsequent onset of acute
      coronary syndrome (ACS). Naturally occurring CD4(+)CD25(+)regulatory T cells
      (nTregs) are indispensable in suppressing the pathological autoreactive immune
      response and maintaining immune homeostasis. However, the number and the
      suppressive function of glycoprotein-A repetitions predominant (GARP) (+) CD4(+)
      CD25(+) activated nTregs were impaired in patients with ACS. Recent evidence
      suggests that heme oxygenase-1 (HO-1) can regulate the adaptive immune response
      by promoting the expression of Foxp3. We therefore hypothesized that HO-1 may
      enhance the function of GARP(+) CD4(+) CD25(+)Tregs in patients with ACS and thus
      regulate immune imbalance. METHODS: T lymphocytes were isolated from healthy
      volunteers (control, n=30) and patients with stable angina (SA, n=40) or ACS
      (n=51). Half of these cells were treated with an HO-1 inducer (hemin) for 48 h,
      and the other half were incubated with complete RPMI-1640 medium. The frequencies
      of T-helper 1 (Th1), Th2, Th17 and latency-associated peptide (LAP) (+)CD4(+) T
      cells and the expression of Foxp3 and GARP by CD4(+)CD25(+)T cells were then
      assessed by measuring flow cytometry after stimulation in vitro. The suppressive
      function of activated Tregs was measured by thymidine uptake. The levels of
      transforming growth factor-1 (TGF-beta1) in the plasma were measured using enzyme
      linked immunosorbent assay (ELISA). The expression levels of the genes encoding
      these proteins were analyzed by real-time polymerase chain reaction. RESULTS:
      Patients with ACS exhibited an impaired number and suppressive function of
      GARP(+) CD4(+) CD25(+)Tregs and a mixed Th1/Th17-dominant T cell response when
      compared with the SA and control groups. The expression of LAP in T cells was
      also lower in patients with ACS compared to patients with SA and the control
      individuals. Treatment with an HO-1 inducer enhanced the biological activity of
      GARP(+) CD4(+) CD25(+)Tregs and resulted in increased expression of LAP and GARP
      by activated T cells. CONCLUSIONS: The reduced number and impaired suppressive
      function of GARP(+) CD4(+) CD25(+)Tregs result in excess effector T cell
      proliferation, leading to plaque instability and the onset of ACS. HO-1 can
      effectively restore impaired GARP(+) CD4(+) CD25(+)Tregs from patients with ACS
      by promoting LAP and GARP expression on activated T cells.

PMID- 25612607
TI  - Bronchogenic stress cardiomyopathy: a case series.
AB  - Despite a growing awareness of stress (takotsubo) cardiomyopathy, the diversity
      in precipitants beyond emotional distress remains under-appreciated. Emerging
      data implicate a differential influence of precipitant type on the variable
      presentations of stress cardiomyopathy. We outline 5 cases of stress
      cardiomyopathy where the precipitant was an acute exacerbation of chronic
      obstructive pulmonary disease treated with high-dose bronchodilator therapy. In
      this setting, an atypical and insidious presentation of the stress cardiomyopathy
      was consistently observed that was difficult to distinguish from the acute airway
      exacerbation itself, with an absence of chest pain in particular. Scrutiny of
      published single-case reports reveals a similar atypical presentation; this
      supports the existence of a novel bronchogenic subgroup of stress cardiomyopathy.
      A key role of repeat ECG evaluation in distinguishing protracted but
      uncomplicated bronchospasm from bronchogenic stress cardiomyopathy is
      highlighted. Further data are now required to examine whether high-dose beta
      agonist therapy is implicated in this association.

PMID- 25612605
TI  - An immunodiagnostic assay for quantitation of specific IgE to the major pollen
      allergen component, Pas n 1, of the subtropical Bahia grass.
AB  - BACKGROUND: Pollens of the Panicoideae subfamily of grasses including Bahia
      (Paspalum notatum) are important allergen sources in subtropical regions of the
      world. An assay for specific IgE to the major molecular allergenic component, Pas
      n 1, of Bahia grass pollen (BaGP) would have immunodiagnostic utility for
      patients with pollen allergy in these regions. METHODS: Biotinylated Pas n 1
      purified from BaGP was coated onto streptavidin ImmunoCAPs. Subjects were
      assessed by clinical history of allergic rhinitis and skin prick test (SPT) to
      aeroallergens. Serum total, BaGP-specific and Pas n 1-specific IgE were measured.
      RESULTS: Pas n 1 IgE concentrations were highly correlated with BaGP SPT (r =
      0.795, p < 0.0001) and BaGP IgE (r = 0.915, p < 0.0001). At 0.23 kU/l Pas n 1
      IgE, the diagnostic sensitivity (92.4%) and specificity (93.1%) for the detection
      of BaGP allergy was high (area under receiver operator curve 0.960, p < 0.0001).
      The median concentrations of Pas n 1 IgE in non-atopic subjects (0.01 kU/l, n =
      67) and those with other allergies (0.02 kU/l, n = 59) showed no inter-group
      difference, whilst grass pollen-allergic patients with allergic rhinitis showed
      elevated Pas n 1 IgE (6.71 kU/l, n = 182, p < 0.0001). The inter-assay
      coefficient of variation for the BaGP-allergic serum pool was 6.92%. CONCLUSIONS:
      Pas n 1 IgE appears to account for most of the BaGP-specific IgE. This molecular
      component immunoassay for Pas n 1 IgE has potential utility to improve the
      sensitivity and accuracy of diagnosis of BaGP allergy for patients in subtropical
      regions.

PMID- 25612608
TI  - Optics. Spatially structured photons that travel in free space slower than the
      speed of light.
AB  - That the speed of light in free space is constant is a cornerstone of modern
      physics. However, light beams have finite transverse size, which leads to a
      modification of their wave vectors resulting in a change to their phase and group
      velocities. We study the group velocity of single photons by measuring a change
      in their arrival time that results from changing the beam's transverse spatial
      structure. Using time-correlated photon pairs, we show a reduction in the group
      velocity of photons in both a Bessel beam and photons in a focused Gaussian beam.
      In both cases, the delay is several micrometers over a propagation distance of ~1
      meter. Our work highlights that, even in free space, the invariance of the speed
      of light only applies to plane waves. 

PMID- 25612609
TI  - Structural biology. Crystal structure of the chemokine receptor CXCR4 in complex
      with a viral chemokine.
AB  - Chemokines and their receptors control cell migration during development, immune
      system responses, and in numerous diseases, including inflammation and cancer.
      The structural basis of receptor:chemokine recognition has been a long-standing
      unanswered question due to the challenges of structure determination for membrane
      protein complexes. Here, we report the crystal structure of the chemokine
      receptor CXCR4 in complex with the viral chemokine antagonist vMIP-II at 3.1
      angstrom resolution. The structure revealed a 1:1 stoichiometry and a more
      extensive binding interface than anticipated from the paradigmatic two-site
      model. The structure helped rationalize a large body of mutagenesis data and
      together with modeling provided insights into CXCR4 interactions with its
      endogenous ligand CXCL12, its ability to recognize diverse ligands, and the
      specificity of CC and CXC receptors for their respective chemokines. 

PMID- 25612610
TI  - Plant development. Genetic control of distal stem cell fate within root and
      embryonic meristems.
AB  - The root meristem consists of populations of distal and proximal stem cells and
      an organizing center known as the quiescent center. During embryogenesis,
      initiation of the root meristem occurs when an asymmetric cell division of the
      hypophysis forms the distal stem cells and quiescent center. We have identified
      NO TRANSMITTING TRACT (NTT) and two closely related paralogs as being required
      for the initiation of the root meristem. All three genes are expressed in the
      hypophysis, and their expression is dependent on the auxin-signaling pathway.
      Expression of these genes is necessary for distal stem cell fate within the root
      meristem, whereas misexpression is sufficient to transform other stem cell
      populations to a distal stem cell fate in both the embryo and mature roots. 

PMID- 25612611
TI  - Unique Roles of TLR9- and MyD88-Dependent and -Independent Pathways in Adaptive
      Immune Responses to AAV-Mediated Gene Transfer.
AB  - The immune system represents a significant barrier to successful gene therapy
      with adeno-associated viral (AAV) vectors. In particular, adaptive immune
      responses to the viral capsid or the transgene product are of concern. The
      sensing of AAV by toll-like receptors (TLRs) TLR2 and TLR9 has been suggested to
      play a role in innate immunity to the virus and may also shape subsequent
      adaptive immune responses. Here, we investigated the functions of TLR2, TLR9 and
      the downstream signaling adaptor MyD88 in antibody and CD8+ T-cell responses.
      Antibody formation against the transgene product occurred largely independently
      of TLR signaling following gene transfer with AAV1 or AAV2 vectors, whereas loss
      of signaling through the TLR9-MyD88 pathway substantially reduced CD8+ T-cell
      responses. In contrast, MyD88 (but neither of the TLRs) regulated antibody
      responses to capsid. B cell-intrinsic MyD88 was required for the formation of
      anti-capsid IgG2c independently of vector serotype or route of administration.
      However, MyD88(-/-) mice instead produced anti-capsid IgG1 that emerged with
      delayed kinetics but nonetheless completely prevented in vivo readministration.
      We conclude that there are distinct roles for TLR9 and MyD88 in promoting
      adaptive immune responses to AAV-mediated gene transfer and that there are
      redundant MyD88-dependent and MyD88-independent mechanisms that stimulate
      neutralizing antibody formation against AAV.

PMID- 25612612
TI  - Impact of the use of bowel for urinary diversion on perioperative complications
      and 90-day mortality in patients aged 75 years or older.
AB  - OBJECTIVE: A potential strategy to decrease the high complication rate of radical
      cystectomy (RC) in the elderly is to avoid the use of bowel for urinary
      diversion. The aim of this study was to address this issue in a multicentre study
      of patients aged >= 75 years. PATIENTS AND METHODS: We performed a retrospective,
      multicentre study of a consecutive series of patients aged >= 75 years who
      underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical,
      surgical and wound complications were graded according to the modified Clavien
      Dindo classification. RESULTS: A total of 256 patients (68% men, mean age 79.6
      years) were analysed. 204 (80%) patients received a urinary diversion with use of
      bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0
      vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007),
      while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with
      UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period
      in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe
      complications graded as Clavien III-V was significantly lower in the UC group
      (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p
      = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1
      vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30-
      and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9,
      5.9 and 6.9% in the bowel cohort, respectively. CONCLUSION: UC following RC is
      associated with a lower complication rate in geriatric patients. The constantly
      increasing cohort of geriatric, multimorbid patients requiring cystectomy might
      justify reconsideration of this form of diversion.

PMID- 25612614
TI  - Non-invasive spectroscopic determination of the antioxidative status of gravidae
      and neonates.
AB  - Pregnancy and postpartum adaptation cause an increased formation of free
      radicals. This is associated with various perinatological diseases, e.g.
      necrotising enterocolitis. The human body has developed a protective system in
      the form of the antioxidative potential. The present study was the first to
      investigate the kinetics of the cutaneous antioxidative status in pregnant women
      and newborns using a non-invasive spectroscopic method. Eighteen pregnant women
      and their babies took part in the study. A light-emitting diode-based compact
      scanner system was used for quick non-invasive measurements of carotenoid
      antioxidants in human skin based on reflection spectroscopy. It could be shown
      that the antioxidative status of the expectant mothers significantly declined
      during labour (p < 0.001) and on day 1 after delivery (p < 0.01). Compared to the
      mothers, the newborns exhibited a significantly higher cutaneous carotenoid
      concentration on both day 1 (p < 0.01) and 5 (p < 0.01) after delivery. These
      results suggest that the oxidative stress due to postpartum adaptation is
      counteracted by an enhanced reservoir of carotenoid antioxidants in the
      subcutaneous fatty tissue. The peripartum cutaneous carotenoid level of mothers
      declines continuously, whereas term newborns show very high cutaneous antioxidant
      values.

PMID- 25612613
TI  - Epidemiology and management of gout in Taiwan: a nationwide population study.
AB  - INTRODUCTION: Gout is the most common inflammatory arthritis worldwide and is the
      only type of chronic arthritis that potentially can be 'cured'. However, data on
      gout incidence, prevalence and management, assessed at multiple time points in
      the same population, are sparse, particularly in Asian populations. The aim of
      this study was to describe trends in the epidemiology of gout in the general
      population of Taiwan. METHODS: The National Health Insurance Research Database
      was used to identify patients with gout and to estimate the prevalence and
      incidence of gout for each calendar year from 2005 to 2010. The pattern of gout
      management was also examined. RESULTS: Of 23,371,362 beneficiaries in 2010, there
      were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence
      of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74
      (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC)
      of the standardised prevalence was -0.7% (95% CI, -1.7% to 0.3%; P=0.14),
      suggesting that the prevalence of gout was essentially the same throughout the
      study period. However, The APC of incidence was -13.4 (95% CI, -16.1 to -10.6)
      between 2005 and 2007 and -2.1 (95% CI, -10.4 to 7.1) between 2007 and 2010.
      Regions with the highest prevalence and incidence were eastern coastal counties
      and offshore islets, where indigenous people are clustered. Among prevalent gout
      cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate
      lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an
      APC of 0.0 (95% CI, -3.8 to 4.0). Uricosuric agents were more commonly prescribed
      than xanthine oxidase inhibitors in Taiwan. CONCLUSIONS: In Taiwan, 1 in 16
      people have gout. Whereas the incidence has decreased recently, the prevalence
      remains unchanged. Management of gout in Taiwan is poor, with only one in five
      affected people being treated with ULT.

PMID- 25612615
TI  - A review on the flexural mode of graphene: lattice dynamics, thermal conduction,
      thermal expansion, elasticity and nanomechanical resonance.
AB  - Single-layer graphene is so flexible that its flexural mode (also called the ZA
      mode, bending mode, or out-of-plane transverse acoustic mode) is important for
      its thermal and mechanical properties. Accordingly, this review focuses on
      exploring the relationship between the flexural mode and thermal and mechanical
      properties of graphene. We first survey the lattice dynamic properties of the
      flexural mode, where the rigid translational and rotational invariances play a
      crucial role. After that, we outline contributions from the flexural mode in four
      different physical properties or phenomena of graphene-its thermal conductivity,
      thermal expansion, Young's modulus and nanomechanical resonance. We explain how
      graphene's superior thermal conductivity is mainly due to its three acoustic
      phonon modes at room temperature, including the flexural mode. Its coefficient of
      thermal expansion is negative in a wide temperature range resulting from the
      particular vibration morphology of the flexural mode. We then describe how the
      Young's modulus of graphene can be extracted from its thermal fluctuations, which
      are dominated by the flexural mode. Finally, we discuss the effects of the
      flexural mode on graphene nanomechanical resonators, while also discussing how
      the essential properties of the resonators, including mass sensitivity and
      quality factor, can be enhanced. 

PMID- 25612616
TI  - Exchange of single amino acids at different positions of a recombinant protein
      affects metabolic burden in Escherichia coli.
AB  - BACKGROUND: Escherichia coli is commonly used in academia and industry for
      expressing recombinant proteins because of its well-characterized molecular
      genetics and the availability of numerous expression vectors and strains. One
      important issue during recombinant protein production is the so-called 'metabolic
      burden': the material and energy normally reserved for microbial metabolism which
      is sapped from the bacterium to produce the recombinant protein. This material
      and energy drain harms biomass formation and modifies respiration. To the best of
      our knowledge, no research has investigated so far whether a single amino acid
      exchange in a recombinant protein affects the metabolic burden phenomenon. Thus,
      in this study, 15 E. coli BL21(DE3) clones expressing either the fusion tags, a
      recombinant wild type lipase, or 13 different lipase variants are investigated to
      quantitatively analyze the respective effects of single amino acid exchanges at
      different positions on respiration, biomass and protein production of each clone.
      Therefore, two small-scale online monitoring systems, namely a Respiration
      Activity MOnitoring System (RAMOS) and a microtiter plate based cultivation
      system (BioLector) are applied. RESULTS: Upon expression of all enzyme variants,
      strong variations were found in the Oxygen Transfer Rate (OTR), biomass and
      protein (lipase) production of the respective E. coli clones. Two distinct
      patterns of respiration behavior were observed and, so, the clones could be
      classified into two groups (Type A and B). Potential factors to explain these
      patterns were evaluated (e.g. plasmid copy number, inclusion body formation).
      However, no decisive factor could yet be identified. Five distinct cultivation
      phases could be determined from OTR curves which give real-time information about
      carbon source consumption, biomass and protein production. In general, it was
      found that the quantity of product increased with the duration of active
      respiration. CONCLUSIONS: This work demonstrates that single amino acid exchanges
      in a recombinant protein influence the metabolic burden during protein
      production. The small-scale online monitoring devices RAMOS and BioLector enable
      the real-time detection of even smallest differences in respiration behavior,
      biomass and protein production in the E. coli clones investigated. Hence, this
      study underscores the importance of parallel online monitoring systems to unveil
      the relevance of single amino acid exchanges for the recombinant protein
      production.

PMID- 25612617
TI  - HOTAIR Long Noncoding RNA Promotes Gastric Cancer Metastasis through Suppression
      of Poly r(C)-Binding Protein (PCBP) 1.
AB  - The objective of this study was to evaluate the role of HOTAIR long noncoding RNA
      in gastric cancer metastasis. We analyzed HOTAIR expression levels by real-time
      reverse transcription PCR and Northern blot analysis in 100 gastric tissues (50
      gastric cancer tissues and 50 adjacent normal mucosa), and in four gastric cancer
      cell lines. Transient RNAi-mediated knockdown and pcDNA-mediated overexpression
      of HOTAIR were performed. Stable shRNA-mediated knockdown and lentiviral-mediated
      overexpression of HOTAIR were to study the role of HOTAIR on in vivo
      tumorigenicity and metastatic burden in the context of xenograft assays.
      Proteomic profiling was performed to decipher differential protein expression in
      cells with different HOTAIR expression levels. One of the differentially
      regulated proteins, Poly r(C)-binding protein (PCBP) 1, was subsequently
      validated and its function evaluated through xenograft assays. Expression of
      HOTAIR was significantly higher in cancerous tissues than in adjacent normal
      mucosa. HOTAIR expression levels dictated in vitro and in vivo tumorigenicity and
      metastatic potential in these cells. PCBP1 and HOTAIR have an inverse
      relationship, both at expression level and in function. A direct interaction
      between the two was confirmed through RNA immunoprecipitation coupled with
      quantitative real-time PCR. PCBP1 was confirmed to be an inhibitor of gastric
      cancer pathogenesis and as functionally opposite to HOTAIR long noncoding RNA. In
      conclusion, HOTAIR expression may serve as a potentially important disease
      biomarker for the identification of high-risk gastric cancer patients. Moreover,
      our findings provide mechanistic evidence for HOTAIR overexpression and PCBP1
      downregulation and the ensuing malignant phenotype in both cultured and xenograft
      gastric cancer cells.

PMID- 25612618
TI  - Vemurafenib resistance signature by proteome analysis offers new strategies and
      rational therapeutic concepts.
AB  - The FDA-approved BRAF inhibitor vemurafenib achieves outstanding clinical
      response rates in patients with melanoma, but early resistance is common.
      Understanding the pathologic mechanisms of drug resistance and identification of
      effective therapeutic alternatives are key scientific challenges in the melanoma
      setting. Using proteomic techniques, including shotgun analysis and 2D-gel
      electrophoresis, we identified a comprehensive signature of the vemurafenib
      resistant M24met in comparison with the vemurafenib-sensitive A375 melanoma cell
      line. The resistant cells were characterized by loss of differentiation,
      induction of transformation, enhanced expression of the lysosomal compartment,
      increased potential for metastasis, migration, adherence and Ca2(+) ion binding,
      enhanced expression of the MAPK pathway and extracellular matrix proteins, and
      epithelial-mesenchymal transformation. The main features were verified by shotgun
      analysis with QEXACTIVE orbitrap MS, electron microscopy, lysosomal staining,
      Western blotting, and adherence assay in a VM-1 melanoma cell line with acquired
      vemurafenib resistance. On the basis of the resistance profile, we were able to
      successfully predict that a novel resveratrol-derived COX-2 inhibitor, M8, would
      be active against the vemurafenib-resistant but not the vemurafenib-sensitive
      melanoma cells. Using high-throughput methods for cell line and drug
      characterization may thus offer a new way to identify key features of vemurafenib
      resistance, facilitating the design of effective rational therapeutic
      alternatives.

PMID- 25612619
TI  - Targeting Three Distinct HER2 Domains with a Recombinant Antibody Mixture
      Overcomes Trastuzumab Resistance.
AB  - HER2 plays an important role in the development and maintenance of the malignant
      phenotype of several human cancers. As such, it is a frequently pursued
      therapeutic target and two antibodies targeting HER2 have been clinically
      approved, trastuzumab and pertuzumab. It has been suggested that optimal
      inhibition of HER2 is achieved when utilizing two or more antibodies targeting
      nonoverlapping epitopes. Superior clinical activity of the trastuzumab plus
      pertuzumab combination in metastatic breast cancer supports this hypothesis.
      Because trastuzumab and pertuzumab were not codeveloped, there may be potential
      for further optimizing HER2 targeting. The study herein evaluated functional
      activity of anti-HER2 antibody combinations identifying optimal epitope
      combinations that provide efficacious HER2 inhibition. High-affinity antibodies
      to all four extracellular domains on HER2 were identified and tested for ability
      to inhibit growth of different HER2-dependent tumor cell lines. An antibody
      mixture targeting three HER2 subdomains proved to be superior to trastuzumab,
      pertuzumab, or a combination in vitro and to trastuzumab in two in vivo models.
      Specifically, the tripartite antibody mixture induced efficient HER2
      internalization and degradation demonstrating increased sensitivity in cell lines
      with HER2 amplification and high EGFR levels. When compared with individual and
      clinically approved mAbs, the synergistic tripartite antibody targeting HER2
      subdomains I, II, and IV demonstrates superior anticancer activity.

PMID- 25612620
TI  - ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3
      56 in Triple-Negative Breast Cancer Cells.
AB  - We previously reported that a pan-PAD inhibitor, YW3-56, activates p53 target
      genes to inhibit cancer growth. However, the p53-independent anticancer activity
      and molecular mechanisms of YW3-56 remain largely elusive. Here, gene expression
      analyses found that ATF4 target genes involved in endoplasmic reticulum (ER)
      stress response were activated by YW3-56. Depletion of ATF4 greatly attenuated
      YW3-56-mediated activation of the mTORC1 regulatory genes SESN2 and DDIT4. Using
      the ChIP-exo method, high-resolution genomic binding sites of ATF4 and CEBPB
      responsive to YW3-56 treatment were generated. In human breast cancer cells, YW3
      56-mediated cell death features mitochondria depletion and autophagy
      perturbation. Moreover, YW3-56 treatment effectively inhibits the growth of
      triple-negative breast cancer xenograft tumors in nude mice. Taken together, we
      unveiled the anticancer mechanisms and therapeutic potentials of the pan-PAD
      inhibitor YW3-56.

PMID- 25612621
TI  - The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate
      immune responses.
AB  - NKR-P1B is a homodimeric type II transmembrane C-type lectinlike receptor that
      inhibits natural killer (NK) cell function upon interaction with its cognate C
      type lectin-related ligand, Clr-b. The NKR-P1B:Clr-b interaction represents a
      major histocompatibility complex class I (MHC-I)-independent missing-self
      recognition system that monitors cellular Clr-b levels. We have generated NKR
      P1B(B6)-deficient (Nkrp1b(-/-)) mice to study the role of NKR-P1B in NK cell
      development and function in vivo. NK cell inhibition by Clr-b is abolished in
      Nkrp1b(-/-) mice, confirming the inhibitory nature of NKR-P1B(B6). Inhibitory
      receptors also promote NK cell tolerance and responsiveness to stimulation;
      hence, NK cells expressing NKR-P1B(B6) and Ly49C/I display augmented
      responsiveness to activating signals vs NK cells expressing either or none of the
      receptors. In addition, Nkrp1b(-/-) mice are defective in rejecting cells lacking
      Clr-b, supporting a role for NKR-P1B(B6) in MHC-I-independent missing-self
      recognition of Clr-b in vivo. In contrast, MHC-I-dependent missing-self
      recognition is preserved in Nkrp1b(-/-) mice. Interestingly, spontaneous myc
      induced B lymphoma cells may selectively use NKR-P1B:Clr-b interactions to escape
      immune surveillance by wild-type, but not Nkrp1b(-/-), NK cells. These data
      provide direct genetic evidence of a role for NKR-P1B in NK cell tolerance and
      MHC-I-independent missing-self recognition.

PMID- 25612622
TI  - Receptor-type tyrosine-protein phosphatase kappa directly targets STAT3
      activation for tumor suppression in nasal NK/T-cell lymphoma.
AB  - Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive disease
      characterized by frequent deletions on 6q, and constitutive activation of signal
      transducer and activator of transcription 3 (STAT3). Phosphorylation at Tyr705
      activates STAT3, inducing dimerization, nuclear translocation, and DNA binding.
      In this study, we investigated whether receptor-type tyrosine-protein phosphatase
      kappa (PTPRK), the only protein tyrosine phosphatase at 6q that contains a STAT3
      specifying motif, negatively regulates STAT3 activation in NKTCL. PTPRK was
      highly expressed in normal NK cells but was underexpressed in 4 of 5 (80%) NKTCL
      cell lines and 15 of 27 (55.6%) primary tumors. Significantly, PTPRK protein
      expression was inversely correlated with nuclear phospho-STAT3(Tyr705) expression
      in NKTCL cell lines (P = .025) and tumors (P = .040). PTPRK restoration decreased
      nuclear phospho-STAT3(Tyr705) levels, whereas knockdown of PTPRK increased such
      levels in NKTCL cells. Phosphatase substrate-trapping mutant assays demonstrated
      the binding of PTPRK to STAT3, and phosphatase assays showed that PTPRK directly
      dephosphorylated phospho-STAT3(Tyr705). Restoration of PTPRK inhibited tumor cell
      growth and reduced the migration and invasion ability of NKTCL cells. Monoallelic
      deletion and promoter hypermethylation caused underexpression of PTPRK messenger
      RNA in NKTCL, and methylation of the PTPRK promoter significantly correlated with
      inferior overall survival (P = .049) in NKTCL patients treated with the steroid
      dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide regimen.
      Altogether, our findings show that PTPRK underexpression leads to STAT3
      activation and contributes to NKTCL pathogenesis. 

PMID- 25612625
TI  - Latent Constructs of the Static-99R and Static-2002R: A Three-Factor Solution.
AB  - The most commonly used risk assessment tools for predicting sexual violence focus
      almost exclusively on static, historical factors (e.g., characteristics of prior
      offences). Consequently, they are assumed to be unable to directly inform the
      selection of treatment targets or evaluate change. In this article, we argue that
      this limitation can be mitigated by using latent variable models as a framework
      to link historical risk factors to the psychological characteristics of
      offenders. Accordingly, we conducted a factor analysis of the 13 nonredundant
      items from the two most commonly used risk tools for sexual offenders (Static-99R
      and Static-2002R) to identify the psychological information contained in these
      tools. Three factors were identified: (a) persistence/paraphilia, a construct
      related to sexual criminality, especially of the pedophilic type; (b) youthful
      stranger aggression, a construct centered on young age and offence seriousness;
      and (c) general criminality, a construct that reflected the diversity and
      magnitude of criminal careers. These constructs predicted sexual recidivism with
      similar accuracy, but only youthful stranger aggression and general criminality
      predicted nonsexual recidivism. These results indicate that risk tools for sexual
      violence are multidimensional, and support a shift from a focus on atheoretical
      risk markers to the assessment of psychologically meaningful constructs. 

PMID- 25612627
TI  - Validating the Accuracy of Reaction Time Assessment on Computer-Based Tablet
      Devices.
AB  - Computer-based assessment has evolved to tablet-based devices. Despite the
      availability of tablets and "apps," there is limited research validating their
      use. We documented timing delays between stimulus presentation and (simulated)
      touch response on iOS devices (3rd- and 4th-generation Apple iPads) and Android
      devices (Kindle Fire, Google Nexus, Samsung Galaxy) at response intervals of 100,
      250, 500, and 1,000 milliseconds (ms). Results showed significantly greater
      timing error on Google Nexus and Samsung tablets (81-97 ms), than Kindle Fire and
      Apple iPads (27-33 ms). Within Apple devices, iOS 7 obtained significantly lower
      timing error than iOS 6. Simple reaction time (RT) trials (250 ms) on tablet
      devices represent 12% to 40% error (30-100 ms), depending on the device, which
      decreases considerably for choice RT trials (3-5% error at 1,000 ms). Results
      raise implications for using the same device for serial clinical assessment of RT
      using tablets, as well as the need for calibration of software and hardware. 

PMID- 25612624
TI  - DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups
      with different clinical and genetic features.
AB  - Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic
      mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic
      aberrations. Epigenetic changes can be pharmacologically reverted; therefore,
      identification of groups of patients with specific epigenomic alterations might
      have therapeutic relevance. Here we integrated genome-wide DNA-promoter
      methylation profiling with gene expression profiling, and clinical and biological
      variables. An unsupervised clustering analysis of a test series of 98 samples
      identified 2 clusters with different degrees of promoter methylation. The cluster
      comprising samples with higher-promoter methylation (High-M) had a poorer overall
      survival compared with the lower (Low-M) cluster. The prognostic relevance of the
      High-M phenotype was confirmed in an independent validation set of 36 patients.
      In the whole series, the High-M phenotype was associated with IGHV1-02 usage,
      mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the
      High-M set, a number of tumor-suppressor genes were methylated and repressed.
      PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and
      overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4)
      identified a poorer-outcome patient subset. Exposure of splenic marginal zone
      lymphoma cell lines to a demethylating agent caused partial reversion of the High
      M phenotype and inhibition of proliferation. 

PMID- 25612626
TI  - Psychometric Comparison of Self- and Informant-Reports of Personality.
AB  - Self-reports are the most relied on assessment method in psychology. In the area
      of personality, informant-reports are a reasonable alternative assessment
      strategy. However, agreement between self- and informant-reports of personality
      is only moderately good. A portion of the observed discrepancies between self-
      and informant-reports of personality may come from differences in psychometric
      measurement across raters. That is, it is unknown whether the constructs assessed
      via self- and informant-reports are psychometrically identical. We examined four
      key personality scales--Well-Being, Social Closeness, Stress Reaction, and Harm
      Avoidance--in male and female dyads who provided self- and informant-reports for
      their partner. Similarities in self- and informant-reports of personality were
      evaluated by testing measurement invariance. Overall, models supported
      configural, metric, and scalar invariance for each of the four personality
      dimensions. These results suggest that the same psychometric constructs are
      assessed via self- and informant-reports of these personality dimensions.
      Informant-reports can be used in studies to avoid biases from relying solely on
      self-reports.

PMID- 25612628
TI  - Fixing the Problem With Empathy: Development and Validation of the Affective and
      Cognitive Measure of Empathy.
AB  - Low empathy is a criterion for most externalizing disorders, and empathy training
      is a regular component of treatment for aggressive people, from school bullies to
      sex offenders. However, recent meta-analytic evidence suggests that current
      measures of empathy explain only 1% of the variance in aggressive behavior. A new
      assessment of empathy was developed to more fully represent the empathy construct
      and better predict important outcomes--particularly aggressive behavior and
      externalizing psychopathology. Across three independent samples (N = 210-708),
      the 36-item Affective and Cognitive measure of Empathy (ACME) was internally
      consistent, structurally reliable, and invariant across sex. The ACME bore
      significant associations to important outcomes, which were incremental relative
      to other measures of empathy and generalizable across sex. Importantly, the
      affective scales of the ACME-particularly a new "Affective Dissonance" scale-
      yielded moderate to strong associations with aggressive behavior and
      externalizing disorders. The ACME is a short, reliable, and useful measure of
      empathy.

PMID- 25612623
TI  - gammadelta T-cell reconstitution after HLA-haploidentical hematopoietic
      transplantation depleted of TCR-alphabeta+/CD19+ lymphocytes.
AB  - We prospectively assessed functional and phenotypic characteristics of gammadelta
      T lymphocytes up to 7 months after HLA-haploidentical hematopoietic stem cell
      transplantation (haplo-HSCT) depleted of alphabeta(+) T cells and CD19(+) B cells
      in 27 children with either malignant or nonmalignant disorders. We demonstrate
      that (1) gammadelta T cells are the predominant T-cell population in patients
      during the first weeks after transplantation, being mainly, albeit not only,
      derived from cells infused with the graft and expanding in vivo; (2) central
      memory cells predominated very early posttransplantation for both Vdelta1 and
      Vdelta2 subsets; (3) Vdelta1 cells are specifically expanded in patients
      experiencing cytomegalovirus reactivation and are more cytotoxic compared with
      those of children who did not experience reactivation; (4) these subsets display
      a cytotoxic phenotype and degranulate when challenged with primary acute myeloid
      and lymphoid leukemia blasts; and (5) Vdelta2 cells are expanded in vitro after
      exposure to zoledronic acid (ZOL) and efficiently lyse primary lymphoid and
      myeloid blasts. This is the first detailed characterization of gammadelta T cells
      emerging in peripheral blood of children after CD19(+) B-cell and alphabeta(+) T
      cell-depleted haplo-HSCT. Our results can be instrumental to the development of
      clinical trials using ZOL for improving gammadelta T-cell killing capacity
      against leukemia cells. This trial was registered at www.clinicaltrials.gov as
      #NCT01810120. 

PMID- 25612629
TI  - The developmental transcriptome of the synanthropic fly Chrysomya megacephala and
      insights into olfactory proteins.
AB  - BACKGROUND: Chrysomya megacephala (Fabricius) is a prevalent and synanthropic
      blowfly which has two sides, for being a pathogenic vector, an efficient
      pollinator, a promising resource of proteins, lipids, chitosan, biofuel et al.,
      and an important forensic indicator. Moreover olfactory proteins are crucial
      component to function in related processes. However, the genomic platform of C.
      megacephala remains relatively unavailable. Developmental transcriptomes of eggs,
      larvae from 1st instar to before pupa stage and adults from emergence to egg
      laying period were built by RNA-sequencing to establish sequence background of C.
      megacephala with special lights on olfactory proteins. RESULTS: Clean reads in
      eggs, larvae and adults were annotated into 59486 transcripts. Transcripts were
      assembled into 22286, 17180, 18934 and 35900 unigenes in eggs, larvae, adults and
      the combined datasets, respectively. Unigenes were annotated using Nr (NCBI non
      redundant protein sequences), Nt (NCBI non-redundant nucleotide sequences), GO
      (Gene Ontology), PFAM (Protein family), KOG/COG (Clusters of Orthologous Groups
      of proteins), Swiss-Prot (A manually annotated and reviewed protein sequence
      database), and KO (KEGG Orthology). Totally 12196 unigenes were annotated into 51
      sub-categories belonging to three main GO categories; 8462 unigenes were
      classified functionally into 26 categories to KOG classifications; 5160 unigenes
      were functionally classified into 5 KEGG categories. Moreover, according to RSEM,
      the number of differentially expressed genes between larvae and eggs, adults and
      eggs, adults and larvae, and the common differentially expressed genes were 2637,
      1804, 2628 and 258, respectively. Among them, 17 odorant-binding proteins (OBPs),
      7 chemosensory proteins (CSPs) and 8 ionotropic receptors (IRs) were differently
      expressed in adults and larvae. Ten were confirmed as significant differentially
      expressed genes. Furthermore, OBP Cmeg32081-c4 was highly expressed in the female
      head and Cmeg33593_c0 were up-regulated with the increase of larval age.
      CONCLUSIONS: A comprehensive sequence resource with desirable quality was built
      by comparative transcriptome of eggs, larvae and adults, enriching the genomic
      platform of C. megacephala. The identified differentially expressed genes would
      facilitate the understanding of metamorphosis, development and the fitness to
      environmental change of C. megacephala. OBP Cmeg32081-c4 and Cmeg33593_c0 might
      play a crucial role in the interactions between olfactory system and biological
      processes.

PMID- 25612630
TI  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in
      women of childbearing age: risks versus benefits.
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor
      blockers (ARBs) are effective and widely used antihypertensive drugs. Exposure to
      these agents is known to be harmful to the fetus in the second and third
      trimesters of pregnancy. Concerns have also been raised about the risk of
      congenital malformations if ACEIs or ARBs are taken during the first trimester of
      pregnancy. The evidence to date, however, is conflicting and observed
      malformations may be due to confounders such as undiagnosed diabetes or maternal
      obesity, other antihypertensive medications or the hypertension itself.
      Nonetheless, in women who become pregnant while taking an ACEI or ARB, the drug
      should be stopped as soon as possible. In women with chronic kidney disease and
      proteinuria, it may be appropriate to continue taking an ACEI or ARB until the
      pregnancy is confirmed because of the significant benefit to their kidney
      function and the lower fertility rate in these patients. 

PMID- 25612631
TI  - Evaluation of lipid peroxidation and oxidative DNA damage in patients with
      periodontitis and hyperlipidemia.
AB  - BACKGROUND: The purpose of this study is to determine the serum levels of
      malondialdehyde (MDA), as a lipid peroxidation marker, and 8
      hydroxydeoxyguanosine (8-OHdG), as an oxidative DNA damage marker, in patients
      with chronic periodontitis (CP) and hyperlipidemia. METHODS: A total of 74
      individuals were divided into four age- and sex-matched groups: 18 patients with
      hyperlipidemia and CP (HLp), 18 periodontally healthy patients with
      hyperlipidemia (HLh), 19 systemically healthy individuals with CP (Cp), and 19
      systemically and periodontally healthy controls (Ch). Clinical periodontal
      parameters were measured, and serum lipids, MDA, and 8-OHdG levels were assessed
      in blood samples. RESULTS: 8-OHdG, MDA, probing depth, clinical attachment level,
      and percentage of sites bleeding on probing (BOP) were significantly higher in
      the HLp group than the Cp group. In the hyperlipidemic group, BOP was
      significantly correlated with total cholesterol, the ratio of total cholesterol
      to high-density lipoprotein cholesterol, and 8-OHdG levels. A significant
      correlation between 8-OHdG and MDA was also observed in the hyperlipidemia group.
      CONCLUSIONS: In this study, serum MDA and 8-OHdG were found to be highest in the
      HLp group. The increased levels of MDA and 8-OHdG in HLp patients may be a result
      of a harmful oxidative status in association with hyperlipidemia and
      periodontitis.

PMID- 25612632
TI  - Periodontal parameters and whole salivary cytokine profiles among habitual gutka
      chewers and non-chewers.
AB  - BACKGROUND: Whole salivary interleukin (IL)-1beta, IL-6, matrix metalloproteinase
      (MMP)-8, and MMP-9 levels among habitual gutka chewers and non-chewers (controls)
      have not been investigated. The aim of the present study is to assess clinical
      periodontal parameters and whole salivary IL-1beta, IL-6, MMP-8, and MMP-9 levels
      among habitual gutka chewers and controls. METHODS: Forty-five gutka chewers and
      45 controls were included. Demographic information regarding age, sex, duration
      and daily frequency of gutka chewing, duration of gutka placement in the mouth,
      and daily toothbrushing habits were collected using a questionnaire. Periodontal
      parameters, including plaque index (PI), bleeding on probing (BOP), probing depth
      (PD) >3 mm, clinical attachment loss (AL), marginal bone loss (MBL), and number
      of missing teeth, were recorded. Unstimulated whole saliva samples were
      collected, and unstimulated whole salivary flow rate (UWSFR) was determined.
      Levels of IL-6, IL-1beta, MMP-8, and MMP-9 were measured in UWS using an enzyme
      linked immunosorbent assay. RESULTS: PI (P <0.01), BOP (P <0.01), PD >3 mm (P
      <0.01), and clinical AL (P <0.01) were significantly higher in gutka chewers than
      controls, as were whole salivary IL-6 (P <0.01), IL-1beta (P <0.01), MMP-8 (P
      <0.01), and MMP-9 (P <0.01) concentrations. There was no significant difference
      in UWSFR, number of missing teeth, or MBL among habitual gutka chewers and
      controls. CONCLUSION: Periodontal inflammatory conditions were worse, and whole
      salivary IL-6, IL-1beta, MMP-8, and MMP-9 levels were higher among gutka chewers
      than non-chewers.

PMID- 25612633
TI  - Synthesis and biological activities of the amide derivative of aplog-1, a
      simplified analog of aplysiatoxin with anti-proliferative and cytotoxic
      activities.
AB  - Aplog-1 is a simplified analog of the tumor-promoting aplysiatoxin with anti
      proliferative and cytotoxic activities against several cancer cell lines. Our
      recent findings have suggested that protein kinase Cdelta (PKCdelta) could be one
      of the target proteins of aplog-1. In this study, we synthesized amide-aplog-1
      (3), in which the C-1 ester group was replaced with an amide group, to improve
      chemical stability in vivo. Unfortunately, 3 exhibited seventy-fold weaker
      binding affinity to the C1B domain of PKCdelta than that of aplog-1, and
      negligible anti-proliferative and cytotoxic activities even at 10(-4) M. A
      conformational analysis and density functional theory calculations indicated that
      the stable conformation of 3 differed from that of aplog-1. Since 27-methyl and
      27-methoxy derivatives (1, 2) without the ability to bind to PKC isozymes
      exhibited marked anti-proliferative and cytotoxic activities at 10(-4) M, 3 may
      be an inactive control to identify the target proteins of aplogs. 

PMID- 25612635
TI  - A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation
      in patients with locally advanced rectal cancer (SHOGUN trial).
AB  - BACKGROUND: The objective of this phase I study was to determine the maximum
      tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy
      (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.
      METHODS: Patients received radiotherapy in a total dose of 50.4 Gy in 28
      fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80
      mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of
      oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was
      initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then
      increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of
      60 mg/m(2)/week until the MTD was attained. RESULTS: Thirteen patients were
      enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of
      six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by
      more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events
      defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and
      29. Twelve patients underwent histologically confirmed R0 resections, and two out
      of six patients (33%) given dose level 3 had pathological complete responses.
      CONCLUSIONS: The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus
      60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy.
      Although our results are preliminary, this new regimen for neoadjuvant
      chemoradiotherapy is considered safe and active. TRIAL REGISTRATION: This trial
      was registered with Clinicaltrials.gov (identifier: NCT01227239 ).

PMID- 25612636
TI  - [Prevalence of autoimmune diseases and microangiopathy in children with diabetes
      type 1 over the years 2000-2010].
AB  - INTRODUCTION: In the past decade the number of patients with type 1 diabetes
      treated with continuous subcutaneous insulin infusion (CSII) has increased
      rapidly. Treatment of the disease is focused on proper physical development and
      the prevention of complications. Aim of the study was to analyze changes in the
      treatment and clinical picture of type 1 diabetes in children over the years 2000
      to 2010 with particular emphasis on the presence of autoimmune diseases and
      microangiopathy. MATERIAL AND METHODS: The study included 567 children diagnosed
      with type 1 diabetes under the care of outpatient diabetes clinic. We compared
      251 children, diabetes outpatient clinic patients in 2000, with 316 children in
      2010. Data were obtained from the outpatient and hospital records. We compared
      baseline demographic, anthropometric data, treatment regimen, type of insulin,
      metabolic control, prevalence of autoimmune diseases and microangipathy. RESULTS:
      In 2010 there was a reduction in the age of diagnosis of diabetes from 10 to 8
      years (p=0.039). Significantly increased the proportion of children treated with
      CSII (up to 60.1%) and decreased the percentage of children using conventional
      insulin for the benefit of insulin analogs. The increase in HbA1c from 7.4 to
      8.0% (p<0.001) has been shown and increase in proportion of patients with HbA1c
      >7.5% in 2010. The percentage of children with obesity increased from 5.2 to
      13.7% (p=0.004) and there was a significant increase in SDS-BMI. The percentage
      of children with autoimmune diseases such as celiac (from 0,4 to 7,3%, p<0,001)
      and thyroid (from 6.9 to 21.3%, p<0.001) has increased. The incidence of
      retinopathy decreased from 6 to 1% (p=0.04), and albuminuria decreased
      insignificantly. CONCLUSIONS: Over the last decade, a significant change in the
      method of treatment in children diagnosed with type 1 diabetes has occurred. The
      deterioration of metabolic control, despite the frequent use in the treatment of
      CSII, may be due to increased frequency of obesity and additional autoimmune
      diseases in today's patients. More similar to physiologic way of insulin infusion
      in nowadays treatment may influence the decrease in the prevalence of
      retinopathy.

PMID- 25612637
TI  - [Analysis of body composition with the use of bioimpedance in children with type
      1 diabetes].
AB  - INTRODUCTION: Patients with diagnosed type 1 diabetes are a group particularly
      exposed to cardiovascular complications related to obesity. According to some
      previous data, one of the useful methods to analyze body composition may be a
      method of bioelectrical impedance. AIM OF THE STUDY: The aim of this research was
      to make an attempt of finding a correlation between anthropometric indicators and
      results of lipids profile and data obtained from bioelectrical impedance tests in
      children with diabetes. MATERIAL AND METHODS: The research sample comprised of
      104 children with diabetes type 1 and 313 children without diabetes (a reference
      group). Anthropometric measurements were made in both groups. Furthermore data
      from lipids profile results was collected, as well as data from bioelectrical
      impedance analysis, such as: percentage and quantity (in kilograms) content of
      adipose tissue, fat-free body mass and total water content in the body. RESULTS:
      The tested and the reference groups were not different in respect of percentage
      content of adipose tissue, fat mass, fat-free body mass and total water content
      in the body. Substantially lower fat mass was noticed among children with
      overweight or obesity and diabetes than in the control children with
      overweight/obesity. In the whole sample a connection between percentage fat
      content and fat mass and standardized body mass index and waist circumference was
      noticed. The connection was stronger in the reference group, than among children
      with diabetes. Correlation between percentage content of adipose tissue with the
      fraction HLD-cholesterol and LDL-cholesterol and values of blood pressure were
      observed in the whole sample. CONCLUSIONS: The results of our research the
      confirm correlation between anthropometric parameters and the data collected from
      bioelectrical impedance. Those connections are, however, stronger in the group of
      children without diabetes than with diabetes, which questions the usefulness of
      this method in evaluation of adipose tissue among children treated with insulin.

PMID- 25612638
TI  - [The degree of health knowledge in children with type 1 diabetes affects the
      metabolic control only in patients with an optimum or suboptimum level of HbA1c].
AB  - INTRODUCTION: The aim of care in type 1 diabetes (T1D) is to achieve a good
      metabolic control decreasing the risk of acute and chronic complications. An
      important element of therapy is health education. AIM OF THE STUDY: The aim of
      the study was to analyze the influence of the level of health knowledge on
      metabolic control and occurrence of acute complications in T1D children.
      MATERIALS AND METHODS: The study involved 100 T1D patients aged 12-18 years. The
      own test was used to check the level of diabetes knowledge and skills of patients
      were evaluated on the basis of practical tasks. Metabolic control assessment was
      based on HbA1c, frequency of acute complications and the incidence and causes of
      hospitalization in the year preceding the study. RESULTS: Patients responded
      correctly to 66% of the questions. The mean level of HbA1c was 8.13-1.75%. Severe
      hypoglycemia occurred in 12 children, diabetic ketoacidosis in 7, 30 patients
      were hospitalized. There was no significant relationship between the level of
      patients' knowledge and HbA1c (p = 0.625). After excluding patients with poorly
      controlled diabetes (HbA1c -9.0%), the relationship between level of health
      knowledge and HbA1c was found (r= -0.26, p=0.022). There was no difference in
      level of knowledge in patients with and without acute complications, and among
      patients who were and were not hospitalized. Among patients with HbA1c <9.0 the
      better level of knowledge was observed in not hospitalized patients compared with
      those requiring hospitalization (23.3-4.9 vs. 20.0-4.2, p=0.038). CONCLUSIONS:
      The level of health knowledge had an influence on metabolic control only in
      children with good or satisfactory HbA1c. Additional operation should be targeted
      to patients with unsatisfactory metabolic control.

PMID- 25612639
TI  - [Nutrigenetics and nutrigenomics - application of ?omics? technologies in
      optimization of human nutrition].
AB  - Nowadays nutrigenetics and nutrigenomics are perceived as one of the most
      important research areas ensuring better understanding of an impact of nutrition
      on human health. Since such researches are interdisciplinary in type, there is a
      problem with their widespread acceptance and practical clinical application of
      obtained results. Understanding the new ideas and hypotheses published in
      researches on nutrigenetics/nutrigenomics requires some knowledge of genetics,
      biochemistry, molecular biology, and capabilities and limitations that are
      associated with the use of statistical and bioinformatic analysis, and above all
      ?omics? research technologies (genomics, transcriptomics, proteomics,
      metabolomics). Highly efficient genome and proteome analysis techniques allow to
      obtain data necessary for profiling of an individual patient. The main problem is
      still our insufficient knowledge of cell physiology and biochemistry. The vast
      amount of information is obtained with the use of ?omics? technologies what makes
      it difficult to interpret and infer. An unquestionable advantage of this type of
      research is the possibility to utilize system analysis (system biology) which is
      important in the context of a holistic interpretation of biological phenomena.
      This review is an attempt to present the main hypotheses and objectives which are
      carried out by researchers in nutrigenetics/nutrigenomics. This article describes
      the most important directions of research and anticipated results that are
      related to the practical use of nutritional genomics as well as the critical
      assessment of the possible impact of future developments on public health. 

PMID- 25612640
TI  - [Bone turnover in children and adolescents with diabetes mellitus type 1].
AB  - Biochemical bone turnover markers are fragments of protein structural elements of
      the bone created during the synthesis or degradation and enzymes specific for
      bone cells, released into the circulation during the metabolic activity of
      osteoblasts and osteoclasts. Bone turnover markers are used as indicators to
      evaluate the activity of modeling and remodeling processes. They are the result
      of the activity of all remodeling processes taking place at the moment in the
      whole skeleton. The assay allows quick assessment of the rate of bone formation
      and resorption processes. Among many complications in children with type 1
      diabetes increased bone turnover leading to a reduction in bone mass may increase
      the risk of osteopenia or osteoporosis in adulthood. The aim of this manuscript
      is to review recent papers about bone turnover in children and adolescents with
      diabetes mellitus type 1. 

PMID- 25612641
TI  - The goiter of a newborn from a mother with Graves' disease.
AB  - INTRODUCTION: Congenital goiter is a rare condition which can be associated with
      both fetal hyper- and hypothyroidism. It may result from different situations in
      maternal-fetal thyroid function because antithyroid medication, iodine as well as
      stimulatory and inhibitory antibodies readily cross the placenta. Aim of the
      study is the presentation of a newborn infant with congenital goiter and neonatal
      thyroid suppression that could be attributed to either an in utero exposure to
      antithyroid drug - propylthiouracil (PTU) or mother's blocking antibodies. CASE
      REPORT: Full term neonate was born with enlarged thyroid and signs (laboratory
      findings) of congenital hypothyroidism. The mother was treated due to
      hyperthyroidism between 8 and 12 week of pregnancy and presented thyroid
      stimulating immunoglobulins (TSI) after delivery. During the treatment with
      replacement doses of L-thyroxin in infancy period no thyroid antibodies in the
      child were detected. CONCLUSIONS: The most probable reason was the negative
      influence of PTU: very high thyroid stimulating hormone (TSH) level since
      delivery and goiter development indicate that fetal hypothyroidism had been
      developing for a long time.

PMID- 25612642
TI  - Venous thromboembolism prophylaxis in ENT surgery: a survey of current practice.
AB  - BACKGROUND: Venous thromboembolism is uncommon in ENT practice. There are no
      specific venous thromboembolism prophylaxis guidelines for ENT surgery, despite
      the bleeding risks associated with ENT surgery and the low incidence of venous
      thromboembolism. METHODS: An online poll of the ENT UK expert panel was conducted
      on the use of venous thromboembolism prophylaxis. RESULTS: A total of 132
      responses were received. Of the respondents, 84.5 per cent routinely assess all
      of their patients for venous thromboembolism risk. In addition, 75.4 per cent use
      local health trust guidelines, with the National Institute for Health and Care
      Excellence being the most common source of national guidelines. There was
      significant heterogeneity in the use of low molecular weight heparin. Only 53.7
      per cent of respondents felt that the guidelines they currently used reflect
      their practice. CONCLUSION: There is significant heterogeneity in venous
      thromboembolism prophylaxis. There is therefore scope for revision of the ENT UK
      venous thromboembolism prophylaxis guidelines to reflect general ENT practice.

PMID- 25612643
TI  - Possible introgression of B chromosomes between bee species (Genus Partamona ).
AB  - The origin of supernumerary (B) chromosomes is still a debated topic, with intra-
      and interspecific origins being the most plausible options. In the bee Partamona
      helleri, a sequence-characterized amplified region (SCAR) marker being specific
      to B chromosomes suggested the possibility of interspecific origin. Here, we
      search for this marker in 3 close relative species and perform DNA sequence
      comparison between species. The SCAR sequence does not show homology with other
      sequences in the databases, but does contain an open reading frame with sequence
      homology with a reverse transcriptase. Dot-blot hybridization using the SCAR
      marker as a probe confirmed that it is present in B-carrying, but not B-lacking
      larvae of P. helleri, and indicated its presence in adult individuals of P.
      cupira and P. criptica. Additionally, PCR amplification of the SCAR marker was
      successful on genomic DNA obtained from P. helleri and P. rustica larvae carrying
      B chromosomes, and on genomic DNA obtained from adult individuals of P. cupira,
      P. criptica and P. rustica. Finally, a comparison of the DNA sequence of the SCAR
      markers amplified from these 4 species showed very few nucleotide differences
      between the species. The complete association between B chromosome and SCAR
      presence and the scarce divergence observed for this DNA sequence between the 4
      species analyzed suggest the possibility that this B chromosome has recently been
      transferred between species through several episodes of interspecific
      hybridization.

PMID- 25612644
TI  - Bone marrow stromal mesenchymal cells induce down regulation of CD20 expression
      on B-CLL: implications for rituximab resistance in CLL.
AB  - Although the majority of B cells express surface CD20 in chronic lymphocytic
      leukaemia (B-CLL), only ~50% of patients respond to treatment with rituximab.
      Decreased CD20 expression on these tumour B cells could be responsible for the
      lack of response observed in some patients treated with rituximab. Despite the
      potential critical role of CD20 in the biology of B cell malignancies, the
      mechanisms controlling its expression are poorly understood. At the bone marrow
      level, mesenchymal stromal cells (MSC) may regulate and support the survival of
      malignant cells, such as B-CLL cells. In this study, we investigated whether MSC
      may regulate the CD20 expression on B-CLL. For this purpose, B cells from CLL
      patients were isolated and co-cultured on MSC. B-CLL cells were collected from B
      CLL/MSC co-cultures and examined for their expression of CD20. We demonstrate
      decreased CD20 expression in B-CLL cells after 2 weeks of co-culture with MSC,
      under contact and non-contact conditions, which was associated with a decreased
      susceptibility to rituximab. Additionally, B cells co-cultured with MSCs show an
      increase in CD59 expression. Our findings strongly suggest that the interaction
      between B-CLL cells and MSC may play a major role in the resistance to rituximab
      induced apoptosis of B-CLL cells.

PMID- 25612646
TI  - Serum Visfatin and Leptin in Relation to Childhood Adiposity and Body Fat
      Distribution: The PIAMA Birth Cohort Study.
AB  - BACKGROUND/AIMS: Visfatin has been suggested as a marker of visceral adiposity.
      We hypothesized that visfatin, but not leptin, would be specifically associated
      with visceral adiposity. We investigated the relation of serum visfatin and
      leptin with measures of adiposity and body fat distribution in children. METHODS:
      Serum leptin and visfatin levels were measured in 1,022 12-year-old children
      participating in the PIAMA birth cohort. BMI, waist, hip and upper arm
      circumference were available for all children. Multiple linear regression
      analyses were conducted to study associations between different anthropometric
      indices and log serum visfatin and leptin levels. RESULTS: All anthropometric
      indices showed positive and strong dose-response relationships with serum leptin.
      Visfatin was increased only in children with a high waist-to-hip ratio. The
      effect size was small compared to those observed for leptin and the association
      was present in overweight children (n = 133) but not in normal weight children.
      CONCLUSION: Serum leptin levels strongly increased with increasing adiposity, but
      were not related to a specific type of fat distribution. In contrast, serum
      visfatin was associated only with high waist-to-hip ratio in overweight children.
      Based on our study we would currently not recommend visfatin as a marker of
      visceral adiposity in the general population of children.

PMID- 25612645
TI  - Liver preservation with machine perfusion and a newly developed cell-free oxygen
      carrier solution under subnormothermic conditions.
AB  - We describe a new preservation modality combining machine perfusion (MP) at
      subnormothermic conditions(21  degrees C) with a new hemoglobin-based oxygen
      carrier (HBOC) solution. MP (n=6) was compared to cold static preservation (CSP;
      n=6) in porcine orthotopic liver transplants after 9 h of cold ischemia and 5-day
      follow-up. Recipients' peripheral blood, serial liver biopsies, preservation
      solutions and bile specimens were collected before, during and after liver
      preservation. Clinical laboratorial and histological analyses were performed in
      addition to mitochondrial functional assays, transcriptomic, metabolomic and
      inflammatory inflammatory mediator analyses. Compared with CSP, MP animals had:
      (1) significantly higher survival (100%vs. 33%; p<0.05); (2) superior graft
      function (p<0.05);(3) eight times higher hepatic O2 delivery than O2 consumption
      (0.78 mL O2/g/h vs. 0.096 mL O2/g/h) during MP; and (4) significantly greater
      bile production (MP=378.5 +/- 179.7; CS=151.6 +/- 116.85). MP downregulated
      interferon (IFN)-alpha and IFN-gamma in liver tissue. MP allografts cleared
      lactate, produced urea, sustained gluconeogenesis and produced hydrophilic bile
      after reperfusion. Enhanced oxygenation under subnormothermic conditions triggers
      regenerative and cell protective responses resulting in improved allograft
      function. MP at 21  degrees C with the HBOC solution significantly improves liver
      preservation compared to CSP.

PMID- 25612647
TI  - Penile cancer stage, survival and body mass index.
AB  - OBJECTIVE: The aim of this study was to determine whether a higher body mass
      index (BMI) in penile cancer patients is associated with more advanced penile
      cancer stage at the time of treatment and cancer survival. METHODS: We evaluated
      433 penile cancer patients treated between 2006 and 2012 at our institute and
      recorded American Joint Committee on Cancer (AJCC) stage, BMI, circumcision,
      smoking and age. A proportional odds model was used to assess a possible
      association between BMI and AJCC stage at diagnosis and controlled for
      circumcision, smoking and age. Five-year disease-specific survival was calculated
      using the Kaplan-Meier method, with the log-rank test assessing equality of
      distributions. RESULTS: 433 patients with a mean BMI of 26.8 kg/m2 were analyzed.
      No statistically significant association between BMI and AJCC stage was found
      (odds ratio 1.01 per 1 kg/m2 increase in BMI, 95% confidence interval 0.97-1.05,
      p=0.63). Differences in disease-specific survival were not observed based on the
      different BMI classes. CONCLUSIONS: No association between BMI of penile cancer
      patients and their disease stage at the time of treatment was observed. Thus, BMI
      at penile cancer treatment does not affect prognosis.

PMID- 25612650
TI  - Lipoxin A4 mediates aortic contraction via RHOA/RHO kinase, endothelial
      dysfunction and reactive oxygen species.
AB  - BACKGROUND: Lipoxin A4 (LXA4) is a biologically active product generated from
      arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced
      by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as
      'aspirin-triggered lipoxin'. LXA4 has both anti-inflammatory and proinflammatory
      actions, the latter being related with reocclusion and restenosis after coronary
      angioplasty in patients treated with aspirin. However, little is known of the
      actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes
      contractile responses and contributes to endothelial dysfunction. METHODS: We
      used aorta from Wistar rats to assess vascular function. Reactive oxygen species
      (ROS) production and contractile and regulatory proteins were investigated.
      RESULTS: LXA4 induced concentration-dependent contractions via formyl peptide
      receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger
      decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H
      oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated
      phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation.
      In the presence of LXA4, ROS production was increased and protein expression of
      RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. CONCLUSION: LXA4
      has a functional role in the vasculature and may contribute to further vascular
      damage in conditions where its production is exacerbated, such as in angioplasty
      associated complications treated with aspirin.

PMID- 25612651
TI  - APRIL induces cisplatin resistance in gastric cancer cells via activation of the
      NF-kappaB pathway.
AB  - BACKGROUND: A proliferation-inducing ligand (APRIL) is a tumor-necrosis factor
      (TNF) family member and is a novel cytokine crucial in sustaining lymphocytic
      leukemia B cell survival and proliferation. However, its role in gastric cancer
      (GC) remains unclear. In this study, we investigated the expression pattern and
      prognostic role of APRIL in GC. METHODS: Expression of APRIL was assessed by
      immunohistochemistry and real-time PCR. Prognostic role of APRIL expression was
      evaluated. We also discovered the effect of APRIL on chemo-resistance in GC cells
      and the underlying mechanisms. RESULTS: APRIL mRNA levels were significantly
      increased in GC tissues compared with adjacent tissues and high expression levels
      of APRIL in tumor cells significantly correlated with poor overall survival in
      patients receiving cisplatin adjuvant treatment. Overexpression of APRIL in AGS
      cells significantly attenuated the therapeutic efficacy of cisplatin in vitro and
      in vivo. In contrast, silence of APRIL in SGC7901 cells enhanced cisplatin
      induced tumor suppression. Our data further revealed that the canonical NF-kappaB
      pathway was involved in APRIL-mediated chemo-resistance. In addition, expression
      of APRIL was regulated by miR-145 in GC cells. CONCLUSION: APRIL is a novel
      clinical chemo-resistance biomarker for gastric cancer and might be a promising
      therapeutic target for GC patients.

PMID- 25612652
TI  - Thyroid cytopathology with an emphasis on the 'atypical cells of uncertain
      significance' category: a 3-year audit with cytohistologic correlation.
AB  - BACKGROUND: The National Cancer Institute meeting of 2007 resulted in the
      reporting terminology for thyroid cytopathology. The Bethesda System for
      Reporting Thyroid Cytopathology (TBSRTC) aims to standardise thyroid
      cytopathology reporting for cytology centres and clinicians alike. STUDY
      OBJECTIVE: To compare our laboratory's performance against TBSRTC. The second aim
      was to determine our laboratory's atypia of undetermined significance/follicular
      cells of undetermined significance (AUS/FLUS) reporting rate and malignant
      outcomes. Our laboratory subclassifies the AUS/FLUS category into AUS/FLUS not
      otherwise specified (NOS) and AUS/FLUS cannot exclude malignancy. MATERIALS: All
      thyroid reports were retrieved from our computerised database for the period of
      January 1, 2008 to March 31, 2011. Histologic correlation was obtained where
      available, and cases were classified according to their original diagnosis into 1
      of the 6 categories of TBSRTC. RESULTS: A total of 1,767 cases were retrieved.
      The categories were as follows: inadequate (n=415; 23%), benign (n=1,063; 60%),
      AUS/FLUS (n=141; 8%) [NOS (n=93; 5%) and cannot exclude malignancy (n=48; 3%)]
      suspicious for follicular/Hurthle cell neoplasm (n=68; 4%), suspicious for
      malignancy (n=37; 2%) and malignant (n=43; 2%). The malignant rates for the
      categories were as follows: -6 (26%), 0 (0%), 8 (40%), 9 (38%), 11 (42%), 15
      (62.5%), and 15 (94%), respectively. CONCLUSION: We have shown that the AUS
      category carries a higher malignant rate than that of the AUS category in TBSRTC
      of 5-15%. We conclude that subclassifying the AUS/FLUS category into NOS and
      cannot exclude malignancy helps to better identify patients with an increased
      risk of malignancy in the AUS/FLUS cannot exclude malignancy category.

PMID- 25612653
TI  - Surface relaxation of Cu(5 1 1).
AB  - The multilayer relaxation of the stepped Cu(5 1 1) surface has been studied by
      quantitative low-energy electron diffraction and analyzed using the CLEED program
      package. Relaxations with respect to the bulk interlayer spacing of 0.6934 A are 
      9.5%, -10.4%, +8.2% and -1.8% for the first four interlayer spacings,
      respectively (negative sign corresponds to contraction). The relaxation sequence
      (- - + -...) is thus in agreement with the theoretical prediction. The deeper
      relaxations are damped in a non-uniform manner and the lateral relaxations are
      smaller than 2% of the lateral spacing. This result agrees well with theoretical
      studies of the same surface. The Pendry R-factor for the favored structure is
      0.21. 

PMID- 25612654
TI  - Eye neoplasms research: a bibliometric analysis from 1966 to 2012.
AB  - PURPOSE: To calculate the growth rate of the biomedical literature on eye
      neoplasms and to assess which journals, countries, and continents are the most
      productive. METHODS: PubMed was used to search for articles published from 1966
      to 2012. Total number of articles per year was fitted to a linear equation as
      well as an exponential curve. To identify the core journals and predict the
      number of journals containing articles related to eye neoplasms, Bradford's law
      was applied. For each country and each continent, the gross domestic product
      (GDP) index (publications per $1 billion USD of GDP) and the population index
      (publications per million inhabitants) were calculated. RESULTS: A total of
      27,943 references were retrieved. The growth in the number of publications showed
      a linear increase with a yearly average growth rate of 2.08%, which was lower
      than for the whole PubMed database (3.59%). Using Bradford's law, 17 core
      journals were identified, among which 2 journals produced more than 1000 articles
      (JAMA Ophthalmology and American Journal of Ophthalmology). Europe was the most
      productive continent, followed by North America and Asia. The United States was
      by far the predominant country in number of publications, followed by Germany and
      the United Kingdom. However, population and GDP indexes showed that absolute
      production did not reflect the production per capita or economic efficiency.
      CONCLUSIONS: This bibliometric study provides data contributing to a better
      understanding of the eye neoplasm research field.

PMID- 25612655
TI  - A proposed biomechanical scale for the diagnosis of corneal ectatic disorders.

PMID- 25612656
TI  - Adult orbital xanthogranulomas: clinical features and management.
AB  - PURPOSE: Adult-onset asthma with periocular xanthogranuloma and adult-onset
      xanthogranuloma are 2 rare subtypes of non-Langerhans cell histiocytic disorder
      and much remains unknown regarding optimal treatment. The authors describe their
      experience in the management of these 2 disease subtypes. METHODS: This is a
      retrospective case series with histopathologically proven orbital xanthogranuloma
      over a period of 12 years. Clinical, imaging, and histopathologic features;
      associated systemic conditions; treatment modality; and outcome during follow-up
      of 6 adult patients who had adult-onset asthma with periocular xanthogranuloma
      and adult-onset xanthogranuloma were reviewed. RESULTS: The age range was 29-75
      years (median 56 years). The duration of symptoms and signs varied from 10 months
      to 9 years. All patients had bilateral and asymmetric involvement. Palpebral
      swelling with yellow discoloration and upper eyelid ptosis were the most common
      signs. Adult-onset asthma was present in 2 patients. Imaging studies demonstrated
      ill-defined infiltrative lesions involving the preseptal area, lacrimal glands,
      extraocular muscles, retrobulbar fat, and optic nerves. The median follow-up was
      50 months. Complete regression of all clinical signs was obtained at 8 months,
      whereas imaging findings disappeared at 18 months with treatment. No recurrence
      was observed. CONCLUSIONS: Treatment consisting of debulking as much affected
      soft tissue as possible followed by a 3-day course of intravenous pulse
      methylprednisolone administration and then by oral prednisone for at least 6
      months may provide adequate regression of the granulomas without recurrence and
      satisfactory cosmesis in patients with adult orbital xanthogranuloma with and
      without asthma.

PMID- 25612657
TI  - Endogenous Histoplasma capsulatum endophthalmitis in an immunocompetent patient.
AB  - PURPOSE: To report on a case of Histoplasma capsulatum endogenous endophthalmitis
      in an immunocompetent patient. METHODS: A 30-year-old patient was admitted with
      floaters and vision impairment of 1 month's duration. He had a history of adrenal
      insufficiency, together with nasal, septum, and soft palate lesions of 3 months;
      duration. Culture results from specimens of these lesions were positive for H
      capsulatum. He was human immunodeficiency virus negative and there was no
      evidence of immunodepression or history of immunosuppression. Fundus examination
      revealed multiple fluffy balls with a string of pearls appearance, 2+ vitreous
      haze, multiple foci of retinochoroiditis inferiorly in the peripheral retina, and
      a 6-disk area lesion of retinochoroiditis at the superotemporal periphery. Due to
      poor response to oral itraconazole, a vitrectomy was performed with an
      intraocular injection of amphotericin B 5 MUg/0.1 mL and removal for a vitreous
      specimen for culture of bacteria and fungi. RESULTS: Vitreous specimen culture of
      the yeast at 28 degrees C grew a white filamentous fungus colony, which was again
      cultured in a brain heart infusion agar medium, where it developed hyaline
      septate hyphae with microconidia and circular macroconidia with double wall,
      which was stained with a lactophenol dye at microscopic examination. The
      macroscopic morphology was consistent with H capsulatum. CONCLUSIONS: Although
      endogenous H capsulatum endophthalmitis is a rare entity, it should be considered
      as a possible etiology even in apparently immunocompetent hosts, especially in
      patients with history of disseminated disease.

PMID- 25612658
TI  - Longitudinal modifications of the Ozurdex intravitreal implant as imaged by SD
      OCT.
AB  - PURPOSE: To describe in vivo longitudinal modifications of the Ozurdex
      intravitreal implant using spectral-domain optical coherence tomography (SD-OCT)
      over a 6-month period in an eye treated for retinal vein occlusion (RVO).
      METHODS: Case report. RESULTS: An 82-year-old woman with severe macular edema
      secondary to branch RVO received an Ozurdex intravitreal implant in the left eye.
      At day 1, SD-OCT showed that the implant was completely filled with highly
      reflective dexamethasone. At day 30, complete resolution of macular edema on SD
      OCT was noted. At day 60, macular edema started to relapse; SD-OCT scans over the
      implant showed highly reflective borders that appeared irregular and focally
      retracted, while the majority of the internal drug had been washed out. At day
      180, macular edema returned to baseline levels; SD-OCT scans over the implant
      showed that the device was contracted with almost complete absence of the
      internal lumen and drug. CONCLUSIONS: Using SD-OCT, we demonstrated that 60 days
      postinjection most dexamethasone had been released from the Ozurdex implant,
      which showed multiple irregularities. This was associated with recurrence of
      macular edema that became worse after 180 days, when there was no residual
      dexamethasone remaining in the shrunken implant. Low steady levels of the drug in
      the vitreous and lower biological activity in the retina after the 2-month high
      dose release phase may explain why a large number of patients lose clinical
      improvement 60 days postinjection, as shown by pivotal clinical trials.

PMID- 25612660
TI  - Acute effects of biventricular pacing in heart failure patients with a normal
      ejection fraction and mechanical dyssynchrony.
AB  - OBJECTIVES: We tested the acute effects of resynchronization in heart failure
      patients with a normal (>50%) left ventricular (LV) ejection fraction (HFNEF) and
      mechanical dyssynchrony. METHODS: Twenty-four HFNEF patients (72 +/- 6 years, 5
      male) with mechanical dyssynchrony (standard deviation of electromechanical time
      delay among 12 LV segments >35 ms) were studied with temporary pacing catheters
      in the right atrium, LV, and right ventricle (RV), and high-fidelity catheters
      for pressure recording. Using selected atrioventricular (AV) intervals of 60, 90,
      120, 150, and 180 ms to optimize transmitral flow during simultaneous
      biventricular pacing, the RV-LV (VV) interval was then evaluated at RV30, RV15,
      0, LV15, LV30, and LV45 (RV or LV indicates which ventricle was paced first, the
      number indicates by how many ms). RESULTS: During simultaneous pacing, longer AV
      intervals were associated with improved LV pressure-derivative minimums and
      increased aortic pressures (p < 0.05 vs. normal sinus rhythm). In the VV interval
      from RV30 to LV45, there was a graded increase in the aortic velocity time
      integral and a decrease in dyssynchrony during simultaneous or LV-first pacing (p
      < 0.05 vs. normal sinus rhythm). CONCLUSIONS: For HFNEF patients with mechanical
      dyssynchrony, acute simultaneous biventricular or LV-first pacing with longer AV
      intervals reduced mechanical dyssynchrony and improved diastolic and systolic
      hemodynamics.

PMID- 25612659
TI  - Biosecurity measures to reduce influenza infections in military barracks in
      Ghana.
AB  - BACKGROUND: Military barracks in Ghana have backyard poultry populations but the
      methods used here involve low biosecurity measures and high risk zoonosis such as
      avian influenza A viruses or Newcastle disease. We assessed biosecurity measures
      intended to minimize the risk of influenza virus infection among troops and
      poultry keepers in military barracks. FINDINGS: We educated troops and used a
      questionnaire to collect information on animal populations and handling practices
      from 168 individuals within 203 households in military barracks. Cloacal and
      tracheal samples were taken from 892 healthy domestic and domesticated wild
      birds, 91 sick birds and 6 water samples for analysis using molecular techniques
      for the detection of influenza A virus. Of the 1090 participants educated and 168
      that responded to a questionnaire, 818 (75%) and 129 (76.8%) respectively have
      heard of pandemic avian influenza and the risks associated with its infection.
      Even though no evidence of the presence of avian influenza infection was found in
      the 985 birds sampled, only 19.5% of responders indicated they disinfect their
      coops regularly and 28% wash their hands after handling their birds. Vaccination
      of birds and use of personal protective clothing while handling the birds were
      low putting the people at risk. CONCLUSION: Though some efforts have been made to
      improve biosecurity practices, interventions that help to protect the poultry
      flock from direct contact have to be practiced. Basic hygiene like washing of
      hands with soap and running water and regular cleaning of chicken coops are
      needed to prevent the spread of diseases among birds and between birds and
      humans.

PMID- 25612662
TI  - On the role of concentration-effect relationships in safety pharmacology: only
      the dose makes a drug not to be poison!

PMID- 25612661
TI  - Development of an efficient conjugation-based genetic manipulation system for
      Pseudoalteromonas.
AB  - Pseudoalteromonas is commonly found throughout the world's oceans, and has gained
      increased attention due to the ecological and biological significance. Although
      over fifty Pseudoalteromonas genomes have been sequenced with an aim to explore
      the adaptive strategies in different habitats, in vivo studies are hampered by
      the lack of effective genetic manipulation systems for most strains in this
      genus. Here, nine Pseudoalteromonas strains isolated from different habitats were
      selected and used as representative strains to develop a universal genetic
      manipulation system. Erythromycin and chloramphenicol resistance were chosen as
      selection markers based on antibiotics resistance test of the nine strains. A
      conjugation protocol based on the RP4 conjugative machinery in E. coli WM3064 was
      developed to overcome current limitations of genetic manipulation in
      Pseudoalteromonas. Two mobilizable gene expression shuttle vectors (pWD2-oriT and
      pWD2Ery-oriT) were constructed, and conjugation efficiency of pWD2-oriT from E.
      coli to the nine Pseudoalteromonas strains ranged from 10(-6) to 10(-3)
      transconjugants per recipient cells. Two suicide vectors, pK18mobsacB-Cm and
      pK18mobsacB-Ery (with sacB for counter-selection), were constructed for gene
      knockout. To verify the feasibility of this system, we selected gene or operon
      that may lead to phenotypic change once disrupted as targets to facilitate in
      vivo functional confirmation. Successful deletions of two genes related to
      prodigiosin biosynthesis (pigMK) in P. rubra DSM 6842, one biofilm related gene
      (bsmA) in P. sp. SM9913, one gene related to melanin hyperproduction (hmgA) in P.
      lipolytica SCSIO 04301 and two flagella-related genes (fliF and fliG) in P. sp.
      SCSIO 11900 were verified, respectively. In addition, complementation of hmgA
      using shuttle vector pWD2-oriT was rescued the phenotype caused by deletion of
      chromosomal copy of hmgA in P. lipolytica SCSIO 04301. Taken together, we
      demonstrate that the vectors and the conjugative protocol developed here have
      potential to use in various Pseudoalteromonas strains. 

PMID- 25612664
TI  - Spotlight on measles in Italy: why outbreaks of a vaccine-preventable infection
      continue in the 21st century.
AB  - Measles is a serious infectious disease that can lead to significant morbidity
      and mortality. Remarkable progress has been made through measles vaccination in
      reducing the number of people dying from measles. In the last years, concerns
      about the safety of vaccines have led to decline in immunization coverage rates
      and new outbreaks of measles in many European countries, including Italy. We
      believe that it is important to reinforce the message that measles vaccine is
      safe and highly effective through appropriate information campaigns and public
      awareness. 

PMID- 25612665
TI  - Sacrococcygeal teratoma with intradural extension: case report.
AB  - Intradural sacrococcygeal teratoma (SCT) is a rare entity that has been reported
      in only a few cases previously. The authors present the case of a 2-week-old,
      otherwise healthy neonate with a mass in the buttock. The imaging findings and
      the high level of serum alpha-fetoprotein were highly suggestive of SCT. On
      operation the authors found intradural extension of the teratoma. The lesion was
      managed successfully without any remaining sequelae. The authors briefly review
      the currently proposed etiology regarding teratoma formation and the intradural
      extension of SCT. 

PMID- 25612663
TI  - Emergence of differentially regulated pathways associated with the development of
      regional specificity in chicken skin.
AB  - BACKGROUND: Regional specificity allows different skin regions to exhibit
      different characteristics, enabling complementary functions to make effective use
      of the integumentary surface. Chickens exhibit a high degree of regional
      specificity in the skin and can serve as a good model for when and how these
      regional differences begin to emerge. RESULTS: We used developing feather and
      scale regions in embryonic chickens as a model to gauge the differences in their
      molecular pathways. We employed cosine similarity analysis to identify the
      differentially regulated and co-regulated genes. We applied low cell techniques
      for expression validation and chromatin immunoprecipitation (ChIP)-based enhancer
      identification to overcome limited cell availabilities from embryonic chicken
      skin. We identified a specific set of genes demonstrating a high correlation as
      being differentially expressed during feather and scale development and
      maturation. Some members of the WNT, TGF-beta/BMP, and Notch family known to be
      involved in feathering skin differentiation were found to be differentially
      regulated. Interestingly, we also found genes along calcium channel pathways that
      are differentially regulated. From the analysis of differentially regulated
      pathways, we used calcium signaling pathways as an example for further
      verification. Some voltage-gated calcium channel subunits, particularly CACNA1D,
      are expressed spatio-temporally in the skin epithelium. These calcium signaling
      pathway members may be involved in developmental decisions, morphogenesis, or
      epithelial maturation. We further characterized enhancers associated with histone
      modifications, including H3K4me1, H3K27ac, and H3K27me3, near calcium channel
      related genes and identified signature intensive hotspots that may be correlated
      with certain voltage-gated calcium channel genes. CONCLUSION: We demonstrated the
      applicability of cosine similarity analysis for identifying novel regulatory
      pathways that are differentially regulated during development. Our study
      concerning the effects of signaling pathways and histone signatures on enhancers
      suggests that voltage-gated calcium signaling may be involved in early skin
      development. This work lays the foundation for studying the roles of these gene
      pathways and their genomic regulation during the establishment of skin regional
      specificity.

PMID- 25612666
TI  - MicroRNA-10b Induces Vascular Muscle Cell Proliferation Through Akt Pathway by
      Targeting TIP30.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes
      significantly to the pathogenesis of atherosclerosis. MiR-10b has recently
      emerged as a critical mediator in regulating cell proliferation in many diseases.
      In our study, miR-10b expression was up-regulated in VSMCs isolated from
      atherosclerotic plaques, as well as in PDGFstimulated VSMCs.Overexpression of miR
      10b promoted cell proliferation of VSMCs. Furthermore, we identified the Tat
      interacting protein 30 (TIP30) as a direct target gene of miR-10b. TIP30 was down
      regulated in VSMCs isolated from atherosclerosis plaques, as well as in
      proliferative VSMCs. Knockdown of TIP30 promoted VSMCs proliferation. In
      addition, miR-10b induced TIP30 down-regulation was accompanied by increased Akt
      phosphorylation. Akt was critical for miR-10b-mediated VSMCs proliferation. Our
      results demonstrated that miR-10b contributed to abnormal VSMCs proliferation
      through inhibiting the Akt pathway by targeting TIP30 in atherosclerosis. The
      modulation of miR-10b in VSMCs provides a potential target for the therapy of
      atherosclerosis. 

PMID- 25612667
TI  - Electrochemical capacitance of Ni-doped metal organic framework and reduced
      graphene oxide composites: more than the sum of its parts.
AB  - Composites of a Ni-doped metal organic framework (MOF) with reduced graphene
      oxide (rGO) are synthesized in bulk (gram scale) quantities. The composites are
      composed of rGO sheets, which avoid restacking from the physical presence of MOF
      crystals. At larger concentration of rGO, the MOF crystals are distributed on the
      overlapping and continuous rGO sheets. Ni in Ni-doped MOF is found to engage in a
      two-electron, reversible, efficient, redox reaction shuttling between Ni and
      Ni(OH)2 in aqueous potassium hydroxide (KOH) electrolyte. The reaction is rather
      unique as Ni-based supercapacitors use a one-electron transfer Faradaic redox
      reaction between Ni(OH)2 and NiO(OH). Employing electrochemical impedance
      spectroscopy, we determined the charge transfer resistance to be 184 mOmega for
      MOF, 74 mOmega for a Ni-doped MOF and 6 mOmega for a rGO-Ni-doped MOF composite,
      but these modifications do not affect the mass transfer resistance. This novel
      redox reaction in conjunction with the lowered charge transfer resistance from
      the introduction of rGO underpins the synergy that dramatically increases the
      capacitance to 758 F/g in the rGO-Ni-doped MOF composite, when the parent MOF
      could store only 100 F/g and a physical composite of rGO and Ni-doped MOF could
      algebraically achieve about 240 F/g. A generic approach of doping MOFs with a
      redox active metal and forming a composite with rGO transforms an electro
      inactive MOF to high capacity energy storage material with energy density of 37.8
      Wh/kg at a power density of 227 W/kg. These results can promote the development
      of high-performance energy storage materials from the wide family of MOFs
      available. 

PMID- 25612669
TI  - The multifactorial interplay of diet, the microbiome and appetite control:
      current knowledge and future challenges.
AB  - The recent availability of high-throughput nucleic acid sequencing technologies
      has rapidly advanced approaches to analysing the role of the gut microbiome in
      governance of human health, including gut health, and also metabolic,
      cardiovascular and mental health, inter alia. Recent scientific studies suggest
      that energy intake (EI) perturbations at the population level cannot account for
      the current obesity epidemic, and significant work is investigating the potential
      role of the microbiome, and in particular its metabolic products, notably SCFA,
      predominantly acetate, propionate and butyrate, the last of which is an energy
      source for the epithelium of the large intestine. The energy yield from dietary
      residues may be a significant factor influencing energy balance. This review
      posits that the contribution towards EI is governed by EI diet composition (not
      just fibre), the composition of the microbiome and by the levels of physical
      activity. Furthermore, we hypothesise that these factors do not exist in a steady
      state, but rather are dynamic, with both short- and medium-term effects on
      appetite regulation. We suggest that the existing modelling strategies for
      bacterial dynamics, specifically for growth in chemostat culture, are of utility
      in understanding the dynamic interplay of diet, activity and microbiomic
      organisation. Such approaches may be informative in optimising the application of
      dietary and microbial therapy to promote health. 

PMID- 25612670
TI  - VAP-B binds to Rab3GAP1 at the ER: its implication in nuclear envelope formation
      through the ER-Golgi intermediate compartment.
AB  - The vesicle-associated membrane protein-associated protein B (VAP-B) is a tail
      anchored protein in the endoplasmic reticulum (ER). VAP-B functions as an adaptor
      protein to recruit target proteins to the ER and execute various cellular
      functions, lipid transport, membrane traffic, ER stress etc. Recently, VAP-B has
      been shown to regulate the nuclear envelope protein transport through the ER
      Golgi intermediate compartment (ERGIC). We showed here that VAP-B directly binds
      to Rab3 GTPase activating protein 1 (Rab3GAP1), the catalytic subunit of Rab3GAP,
      through the two phenylalanines (FF) in an acidic tract (FFAT)-like motif of
      Rab3GAP1. Rab3GAP consists of two subunits, the catalytic subunit Rab3GAP1 and
      the non-catalytic subunit Rab3GAP2. VAP-B binds to Rab3GAP1 even in the
      Rab3GAP1/2 heterodimer complex. A single amino acid substitution of the FFAT-like
      motif reduces the binding activity of Rab3GAP1 to VAP-B. On the other hand, the
      FFAT-like motif mutation increases the binding activity of Rab3GAP1 to ERGIC-53,
      the ERGIC marker protein. Overexpression of Rab3GAP1 affects nuclear envelope
      formation more potently than that of Rab3GAP1 FFAT-like motif mutant. These
      results suggest that the binding of VAP-B to Rab3GAP1 is implicated in the
      regulation of nuclear envelope formation through ERGIC. 

PMID- 25612671
TI  - Identification and characterization of TMEM33 as a reticulon-binding protein.
AB  - Endoplasmic reticulum (ER) is an organelle that has an elaborate and continuous
      membrane system composed of sheet-like cisternae and a network of interconnected
      tubules. The ER tubules are shaped by reticulons, a conserved ER membrane protein
      family. However, how the membrane-shaping activity is regulated remains to be
      elucidated. To understand the mode of action of reticulons, we isolated TMEM33, a
      conserved protein harboring three transmembrane domains, as a reticulon 4C
      binding protein by affinity chromatography. In addition to reticulon 4C, TMEM33
      binds to reticulon 1A, -2B, -3C and a reticulon homology domain-containing
      protein Arl6IP1. Exogenously expressed TMEM33 localizes at both the ER membrane
      and the nuclear envelope. Exogenously expressed TMEM33 co-localizes with
      exogenously expressed reticulon 4C well at the ER sheets and partially at the ER
      tubules. Exogenously expressed TMEM33 suppresses the exogenously expressed
      reticulon 4C-induced tubulation of ER. These results suggest that TMEM33 has a
      potency to suppress the membrane-shaping activity of reticulons, thereby
      regulating the tubular structure of ER. 

PMID- 25612673
TI  - Coexistence of endometrioid adenocarcinoma in atypical polypoid adenomyoma.
AB  - Atypical polypoid adenomyoma (APA) is a rare polypoid tumor of the uterus
      composed of atypical endometrial glands and smooth muscle cells. Concomitant
      development of endometrial adenocarcinoma in APA remains infrequent. We report a
      case of the coexistence of endometrioid adenocarcinoma in APA. A 41-year-old
      patient presented with abnormal genital bleeding. A polypoid mass was extruded
      from the external cervical os. She underwent transcervical resection of the
      polypoid mass arising from the lower uterine segment. Pathological examination
      revealed APA with the foci of well-differentiated endometrioid adenocarcinoma.
      Subsequently, she underwent total hysterectomy and bilateral salpingo
      oophorectomy. No residual malignant lesions were found. Awareness of the close
      association of APA with the development of endometrial cancer is warranted. A
      meticulous pathological evaluation of specimen of APA is necessary for the
      detection of the coexistence of endometrial cancer. 

PMID- 25612674
TI  - Development and mapping of CL-repeat display markers on the maize B chromosome.
AB  - The CL-repeat is a repetitive sequence that is unique to the maize B chromosome,
      where it resides in the centromeric knob and the first 3 distal heterochromatic
      regions of the long arm. Given this organization, it would be desirable to
      identify molecular markers that are specifically distributed in the B chromosome.
      In this report, the CL-repeat has been used to develop a class of molecular
      markers for the maize B chromosome. To this end, a modified transposon display
      procedure designated as CL-repeat display was used to generate and display 26
      genomic fragments that are specific to the B chromosome, all of which were cloned
      and sequenced. The sequences of 19 fragments were highly homologous to the 5' or
      3' terminus of the CL-repeat. Five of these fragments also contained sequences
      that were homologous to sequences of the B chromosome centromere. Four of the
      other 7 fragments shared homology with B chromosome centromere sequences, and the
      remaining 3 were of unidentified sequences. Using 13 B-10L translocations with
      various breakpoints along the B chromosome long arm, the 26 CL-repeat display
      markers were mapped to definite regions of the B chromosome. This strategy should
      be feasible for the development of molecular markers for the B chromosome in
      maize and in other species where B chromosome-specific repeats have been
      identified.

PMID- 25612672
TI  - Pathogenesis of combined high-grade squamous intraepithelial lesion and
      adenocarcinoma in situ of the uterine cervix: human papillomavirus genotype and
      methylation status and immunohistochemical study.
AB  - To determine the etiology of combined high-grade squamous intraepithelial lesion
      (HSIL) and adenocarcinoma in situ (AIS) of the uterine cervix, we examined human
      papillomavirus (HPV) subtypes, methylation status of the HPV-16 L1 gene, and
      immunohistochemical staining pattern of Krt7 in 8 cases of combined HSIL and AIS.
      Overall, 6 (75%) of 8 patients with combined HSIL and AIS were infected by the
      same subtype of HPV in both HSIL and AIS (cases 1-5, HPV-16; and case 6, HPV-18),
      whereas 2 (25%) patients showed infection with different subtypes of HPV (case 7,
      HPV-31 and -18; and case 8, HPV-52 and -16, in HSIL and AIS, respectively). The
      degrees of methylation at CpG islands within the HPV-16 L1 gene were almost
      equivalent between HSIL and AIS in cases 1-4, whereas a great difference in CpG
      methylation patterns between two was seen in only 1 case (case 5). In addition,
      both patients infected with different subtypes of HPV between HSIL and AIS were
      positive for Krt7 only within the AIS component. Based on these results, we
      propose two distinct developmental pathways of combined HSIL and AIS of the
      uterine cervix, the common pathway and the individual pathway. 

PMID- 25612676
TI  - A Continuous Metabolic Syndrome Score Is Associated with Specific Biomarkers of
      Inflammation and CVD Risk in Prepubertal Children.
AB  - BACKGROUND/AIMS: We aimed to evaluate the use of a continuous metabolic syndrome
      (MetS) score and to assess the associations of this score with risk biomarkers of
      inflammation, endothelial damage and cardiovascular disease (CVD) in prepubertal
      children. METHODS: A total of 677 prepubertal children (295 obese, 146
      overweight, and 236 normal-weight) were recruited. MetS traits, markers of
      inflammation, endothelial damage and CVD risk were measured, and a continuous
      MetS score was calculated, consisting of the sum/5 of the standardised scores of
      the MetS components. RESULTS: The continuous MetS score was significantly
      associated with active plasminogen activator inhibitor-1 (r = 0.406, p < 0.001),
      adiponectin (r = -0.212, p < 0.001), resistin (r = 0.263, p < 0.001), C-reactive
      protein (r = 0.254, p < 0.001), tumour necrosis factor alpha (r = 0.120, p =
      0.003), myeloperoxidase (r = 0.188, p < 0.001) and sE-selectin (r = 0.278, p <
      0.001). Children in the normal-weight, overweight and obese groups with MetS
      totalled 0 (0%), 1 (0.7%) and 24 (8.7%), respectively, whereas the at-risk
      children identified using the continuous MetS score in each group totalled 2
      (0.85%), 17 (11.6%) and 167 (56.6%), respectively. CONCLUSIONS: The association
      of the continuous MetS score with specific risk biomarkers of inflammation,
      endothelial damage and CVD supports its use in the early identification of
      children at increased risk of metabolic dysfunction.

PMID- 25612677
TI  - Estrogen receptors alpha and beta have different roles in the induction and
      trafficking of progesterone receptors in hypothalamic ventromedial neurons.
AB  - Progesterone receptor (PR) activation in the ventrolateral division of the
      hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female
      sexual behavior. Estrogen receptor (ER) alpha, in contrast to ERbeta, has been
      implicated in the induction of PRs. The simultaneous activation of ERalpha and
      ERbeta, although not increasing the number of PR-immunoreactive neurons in the
      VMNvl, facilitates lordosis, which suggests that ERbeta and/or the ERalpha-ERbeta
      interaction might play a role in PR dynamics and/or PR expression by individual
      neurons. To address this question, we used western blot and immunohistochemical
      studies to determine the amounts and subcellular distributions of both PR
      isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate
      or with specific agonists of ERalpha and ERbeta, alone or in association. The
      present data show that ERalpha activation does not change PR expression in
      individual neurons, but increases the number of PRs in the VMNvl, because it
      increases the number of neurons expressing PRs. Conversely, ERbeta activation
      does not change the total number of PRs in the VMNvl, but increases the labeling
      intensity of the perikaryal cytoplasm, which suggests that it promotes the
      transport of PRs from neurites into cell bodies. In addition, the simultaneous
      activation of ERalpha and ERbeta increases the expression of PRs by individual
      neurons and, consequently, increases the total number of PRs in the VMNvl. Our
      findings reveal that individual and simultaneous activation of ERalpha and ERbeta
      have different effects on the levels and subcellular location of PRs in VMNvl
      neurons. 

PMID- 25612675
TI  - RUNX3 promoter hypermethylation is frequent in leukaemia cell lines and
      associated with acute myeloid leukaemia inv(16) subtype.
AB  - Correlative and functional studies support the involvement of the RUNX gene
      family in haematological malignancies. To elucidate the role of epigenetics in
      RUNX inactivation, we evaluated promoter DNA methylation of RUNX1, 2, and 3 in 23
      leukaemia cell lines and samples from acute myeloid leukaemia (AML), acute
      lymphocytic leukaemia (ALL) and myelodysplatic syndromes (MDS) patients. RUNX1
      and RUNX2 gene promoters were mostly unmethylated in cell lines and clinical
      samples. Hypermethylation of RUNX3 was frequent among cell lines (74%) and highly
      variable among patient samples, with clear association to cytogenetic status.
      High frequency of RUNX3 hypermethylation (85% of the 20 studied cases) was found
      in AML patients with inv(16)(p13.1q22) compared to other AML subtypes (31% of the
      other 49 cases). RUNX3 hypermethylation was also frequent in ALL (100% of the six
      cases) but low in MDS (21%). In support of a functional role, hypermethylation of
      RUNX3 was correlated with low levels of protein, and treatment of cell lines with
      the DNA demethylating agent, decitabine, resulted in mRNA re-expression.
      Furthermore, relapse-free survival of non-inv(16)(p13.1q22) AML patients without
      RUNX3 methylation was significantly better (P = 0.016) than that of methylated
      cases. These results suggest that RUNX3 silencing is an important event in
      inv(16)(p13.1q22) leukaemias. 

PMID- 25612679
TI  - Inhibition of Testosterone Aromatization by the Indole-3-carbinol Derivative CTet
      in CYP19A1-overexpressing MCF-7 Breast Cancer Cells.
AB  - Natural products such as aromatase inhibitors have been the object of growing
      attention in recent years because of their potential to inhibit aromatase with
      fewer side effects and the possible translation of their current use as
      chemotherapeutic agents to future clinical applications in breast cancer
      chemoprevention. We have previously investigated CTet, a novel anticancer agent
      obtained from the broccoli-derived compound indole-3- carbinol (I3C), that shows
      great anticancer potential in both in vitro and in vivo studies. Here we
      evaluated the potential of CTet as a chemopreventive agent in aromatase
      expressing MCF-7/AROM-1 breast cancer cells. The testosterone (TE) aromatization
      in estradiol (E2) was indirectly evaluated in terms of inhibition of TE-induced
      cell proliferation, ERalpha phosphorylation/activation and Bcl-2 and IGF-1R ERE
      regulated protein accumulation. Our results showed that CTet inhibited TE-driven
      ERalpha phosphorylation of both cytosolic and nuclear ERalpha pools, suggesting
      an inhibitory effect of TE aromatization in E2. CTet did not inhibit E2-driven
      nuclear ERalpha phosphorylation, but partially inhibited E2-driven cytosolic
      ERalpha phosphorylation. Moreover, CTet inhibited Bcl-2 and IGF-1R accumulation
      induced by TE but not that which was induced by E2. A cell-free enzymatic assay
      showed that CTet did not inhibit aromatase activity directly; however, since CTet
      treatment induced endoplasmic reticulum stress, the TE aromatization could be
      affected because the aromatase enzyme is located within the endoplasmic
      reticulum. Finally, CTet and letrozole synergistically inhibited TE-induced cell
      proliferation. These results showed the potential of the I3C derivative CTet as a
      chemopreventive agent that interferes with aromatase activity. 

PMID- 25612678
TI  - Quercetin Increase the Chemosensitivity of Breast Cancer Cells to Doxorubicin Via
      PTEN/Akt Pathway.
AB  - Our previous study indicated that nontoxic doses of quercetin (Que) could
      increase the chemosensitivity of breast cancer cells to doxorubicin (Dox)
      although the mechanism still remains elusive. Therefore, in this study, we aimed
      to investigate the underlying mechanisms. MCF-7 cells and MCF-7/dox cells were
      exposed to PTEN inhibitor bpV (HOpic), Dox, or combination of Dox and Que with or
      without bpV (HOpic) intervention for 24 hours. Cell proliferation, cell
      apoptosis, cell invasion and expression of PTEN and phospho-Akt (p-Akt) were then
      assessed. bpV (HOpic) had little effect on cell proliferation at concentrations
      less than 1 MUM. Compared to treatment with Dox alone, combined treatment with
      Dox and Que significantly inhibited cell proliferation and invasion, increased
      cell apoptosis, up-regulated the expression of PTEN and down-regulated the
      expression of p-Akt. However, co-treatment with PTEN inhibitor bpV (HOpic) could
      revert the effects of Que on Dox. These data indicate that Que can increase the
      sensitivity of breast cancer cells to Dox through down regulation of p-Akt
      expression arising from increased expression of PTEN. 

PMID- 25612680
TI  - Discovery of Novel N-alkyl 4-anilinofuro[2,3-b]quinoline Derivatives (CIL-102
      Derivatives) Against Castration-resistant Human Prostate Cancers.
AB  - A number of N-alkylated 4-anilinofuro[2,3-b]quinoline derivatives were
      synthesized and evaluated in vitro against PC-3, A549, and MCF-7 cancer cells and
      M-10 normal human mammary epithelial cells. The known antimitotic CIL-102 was
      moderately active against the growth of PC-3 prostate cancer cells with an IC50
      value of 2.69 MUM while it was more potent against the growth of A549, MCF-7 and
      M-10 cells with IC50 values of 0.61, 0.31 and 0.95 MUM, respectively. However,
      the cytotoxic profiles of its N-alkylated derivatives, 6a - 6c, were reversed and
      strongly inhibited PC-3 cell growth with IC50 values of less than 1.0 MUM but
      only weakly against the growth of A549, MCF-7 and M-10 cells. These results
      indicated that N-alkylation of CIL-102 increased not only selectivity but also
      the antiproliferative potency against PC-3 cell growth. Among these derivatives
      synthesized, N-(4-acetylphenyl)-N-(furo[2,3-b]quinolin- 4-yl)methylamine (6a) and
      its N-ethyl counterpart 6b are the two most active CIL-102 derivatives against PC
      3 cell growth with IC50 value of 0.22 and 0.20 MUM, respectively. Compound 6a is
      less cytotoxic to normal human M-10 cells than 6b and therefore was selected for
      further mechanism studies. The flow cytometry studies clearly indicated that
      compound 6a induced cell accumulation in G2/M phase in a dose-dependent manner
      after 24 h-treatment. While the proliferation of LNCaP C-81 prostate cancer cells
      was also strongly suppressed by compound 6a; compound 11a exhibited better
      selective activity toward LNCaP C-81 prostate cancer cells over RWPE-1 non
      cancerous prostate epithelia. Thus, this group of compounds has a potential of
      serving as therapeutic agents toward advanced castration-resistant prostate
      cancers.

PMID- 25612681
TI  - MicroRNAs and Targeted Therapies in Non-small Cell Lung Cancer: Minireview.
AB  - The discovery of driver oncogene alterations in non-small cell lung cancer
      (NSCLC), such as EGFR, EML4-ALK, MET and RAS, as well as the identification of
      their specific targeted inhibitors have led to new opportunities for treatment of
      this tumor. Drug resistance, intrinsic or acquired, represents the major cause of
      failure of novel biological agents. MicroRNAs (miRNAs) are a family of small non
      coding RNAs that can silence their cognate target genes by specifically binding
      mRNAs or inhibiting their translation. The recent evidences that several micro
      RNAs can modulate the oncogenic driver pathways in NSCLC and that they are
      involved in drug resistance of their targeted inhibitors, have paved the way for
      new therapeutic strategies. This minireview aims 1) to explore the potential
      mechanisms by which key miRNAs may up-regulate or down-regulate specific
      oncogenic driver pathways; 2) highlight the role of microRNAs in the mechanisms
      of resistance to targeted therapies; 3) discuss the therapeutic potential by
      using short-interfering RNAs or artificial miRNAs as anti-cancer therapies. 

PMID- 25612683
TI  - On the edge energy of lipid membranes and the thermodynamic stability of pores.
AB  - To perform its barrier function, the lipid bilayer membrane requires a robust
      resistance against pore formation. Using a self-consistent field (SCF) theory and
      a molecularly detailed model for membranes composed of charged or zwitterionic
      lipids, it is possible to predict structural, mechanical, and thermodynamical
      parameters for relevant lipid bilayer membranes. We argue that the edge energy in
      membranes is a function of the spontaneous lipid monolayer curvature, the mean
      bending modulus, and the membrane thickness. An analytical Helfrich-like model
      suggests that most bilayers should have a positive edge energy. This means that
      there is a natural resistance against pore formation. Edge energies evaluated
      explicitly in a two-gradient SCF model are consistent with this. Remarkably, the
      edge energy can become negative for phosphatidylglycerol (e.g.,
      dioleoylphosphoglycerol) bilayers at a sufficiently low ionic strength. Such
      bilayers become unstable against the formation of pores or the formation of lipid
      disks. In the weakly curved limit, we study the curvature dependence of the edge
      energy and evaluate the preferred edge curvature and the edge bending modulus.
      The latter is always positive, and the former increases with increasing ionic
      strength. These results point to a small window of ionic strengths for which
      stable pores can form as too low ionic strengths give rise to lipid disks. Higher
      order curvature terms are necessary to accurately predict relevant pore sizes in
      bilayers. The electric double layer overlap across a small pore widens the window
      of ionic strengths for which pores are stable. 

PMID- 25612682
TI  - Thrombotic responses of endothelial outgrowth cells to protein-coated surfaces.
AB  - There is significant clinical need for viable small-diameter vascular grafts.
      While there are many graft biomaterials in development, few have been clinically
      successful. Evaluation of grafts with a clinically relevant model is needed to
      drive development. This work examined extracellular matrix coatings on the
      thrombotic phenotype of endothelial outgrowth cells (EOCs). EOCs were tested on
      flat plates and tubular grafts. Flat plate studies examined collagen I, collagen
      IV, fibronectin and alpha-elastin coatings. EOCs attached or proliferated more
      readily on collagen I and fibronectin surfaces as determined by total DNA. The
      production of activated protein C (APC) by EOCs was also dependent on the surface
      coating, with collagen I and fibronectin displaying a higher activity than both
      collagen IV and alpha-elastin on flat plate studies. Based on these results, only
      collagen I and fibronectin coatings were tested on expanded
      polytetrafluoroethylene (ePTFE) in the ex vivo model. Tubular samples showed
      significantly greater tissue factor pathway inhibitor gene expression on collagen
      I than on fibronectin. Platelet adhesion was not significantly different, but
      EOCs on collagen I produced significantly lower APC than on fibronectin,
      suggesting that differences exist between the flat plate and tubular cultures.
      Overall, while the hemostatic phenotype of EOCs displayed some differences, cell
      responses were largely independent of the matrix coating. EOCs adhered strongly
      to both fibronectin- and collagen-I-coated ePTFE grafts under ex vivo (100
      ml/min) flow conditions suggesting the usefulness of this clinically relevant
      cell source, testing modality, and shunt model for future work examining
      biomaterials and cell conditioning before implantation.

PMID- 25612684
TI  - The ab-initio density matrix renormalization group in practice.
AB  - The ab-initio density matrix renormalization group (DMRG) is a tool that can be
      applied to a wide variety of interesting problems in quantum chemistry. Here, we
      examine the density matrix renormalization group from the vantage point of the
      quantum chemistry user. What kinds of problems is the DMRG well-suited to? What
      are the largest systems that can be treated at practical cost? What sort of
      accuracies can be obtained, and how do we reason about the computational
      difficulty in different molecules? By examining a diverse benchmark set of
      molecules: pi-electron systems, benchmark main-group and transition metal dimers,
      and the Mn-oxo-salen and Fe-porphine organometallic compounds, we provide some
      answers to these questions, and show how the density matrix renormalization group
      is used in practice. 

PMID- 25612686
TI  - Towards an exact theory of linear absorbance and circular dichroism of pigment
      protein complexes: importance of non-secular contributions.
AB  - A challenge for the theory of optical spectra of pigment-protein complexes is the
      equal strength of the pigment-pigment and the pigment-protein couplings. Treating
      both on an equal footing so far can only be managed by numerically costly
      approaches. Here, we exploit recent results on a normal mode analysis derived
      spectral density that revealed the dominance of the diagonal matrix elements of
      the exciton-vibrational coupling in the exciton state representation. We use a
      cumulant expansion technique that treats the diagonal parts exactly, includes an
      infinite summation of the off-diagonal parts in secular and Markov
      approximations, and provides a systematic perturbative way to include non-secular
      and non-Markov corrections. The theory is applied to a model dimer and to
      chlorophyll (Chl) a and Chl b homodimers of the reconstituted water-soluble
      chlorophyll-binding protein (WSCP) from cauliflower. The model calculations
      reveal that the non-secular/non-Markov effects redistribute oscillator strength
      from the strong to the weak exciton transition in absorbance and they diminish
      the rotational strength of the exciton transitions in circular dichroism. The
      magnitude of these corrections is in a few percent range of the overall signal,
      providing a quantitative explanation of the success of time-local convolution
      less density matrix theory applied earlier. A close examination of the optical
      spectra of Chl a and Chl b homodimers in WSCP suggests that the opening angle
      between Qy transition dipole moments in Chl b homodimers is larger by about 9(?)
      than for Chl a homodimers for which a crystal structure of a related WSCP complex
      exists. It remains to be investigated whether this change is due to a different
      mutual geometry of the pigments or due to the different electronic structures of
      Chl a and Chl b. 

PMID- 25612685
TI  - Hybrid pathwise sensitivity methods for discrete stochastic models of chemical
      reaction systems.
AB  - Stochastic models are often used to help understand the behavior of intracellular
      biochemical processes. The most common such models are continuous time Markov
      chains (CTMCs). Parametric sensitivities, which are derivatives of expectations
      of model output quantities with respect to model parameters, are useful in this
      setting for a variety of applications. In this paper, we introduce a class of
      hybrid pathwise differentiation methods for the numerical estimation of
      parametric sensitivities. The new hybrid methods combine elements from the three
      main classes of procedures for sensitivity estimation and have a number of
      desirable qualities. First, the new methods are unbiased for a broad class of
      problems. Second, the methods are applicable to nearly any physically relevant
      biochemical CTMC model. Third, and as we demonstrate on several numerical
      examples, the new methods are quite efficient, particularly if one wishes to
      estimate the full gradient of parametric sensitivities. The methods are rather
      intuitive and utilize the multilevel Monte Carlo philosophy of splitting an
      expectation into separate parts and handling each in an efficient manner. 

PMID- 25612687
TI  - Short-range stabilizing potential for computing energies and lifetimes of
      temporary anions with extrapolation methods.
AB  - The energy of a temporary anion can be computed by adding a stabilizing potential
      to the molecular Hamiltonian, increasing the stabilization until the temporary
      state is turned into a bound state, and then further increasing the stabilization
      until enough bound state energies have been collected so that these can be
      extrapolated back to vanishing stabilization. The lifetime can be obtained from
      the same data, but only if the extrapolation is done through analytic
      continuation of the momentum as a function of the square root of a shifted
      stabilizing parameter. This method is known as analytic continuation of the
      coupling constant, and it requires--at least in principle--that the bound-state
      input data are computed with a short-range stabilizing potential. In the context
      of molecules and ab initio packages, long-range Coulomb stabilizing potentials
      are, however, far more convenient and have been used in the past with some
      success, although the error introduced by the long-rang nature of the stabilizing
      potential remains unknown. Here, we introduce a soft-Voronoi box potential that
      can serve as a short-range stabilizing potential. The difference between a
      Coulomb and the new stabilization is analyzed in detail for a one-dimensional
      model system as well as for the (2)Piu resonance of CO2(-), and in both cases,
      the extrapolation results are compared to independently computed resonance
      parameters, from complex scaling for the model, and from complex absorbing
      potential calculations for CO2(-). It is important to emphasize that for both the
      model and for CO2(-), all three sets of results have, respectively, been obtained
      with the same electronic structure method and basis set so that the theoretical
      description of the continuum can be directly compared. The new soft-Voronoi-box
      based extrapolation is then used to study the influence of the size of diffuse
      and the valence basis sets on the computed resonance parameters.

PMID- 25612688
TI  - Sublinear scaling for time-dependent stochastic density functional theory.
AB  - A stochastic approach to time-dependent density functional theory is developed
      for computing the absorption cross section and the random phase approximation
      (RPA) correlation energy. The core idea of the approach involves time-propagation
      of a small set of stochastic orbitals which are first projected on the occupied
      space and then propagated in time according to the time-dependent Kohn-Sham
      equations. The evolving electron density is exactly represented when the number
      of random orbitals is infinite, but even a small number (~16) of such orbitals is
      enough to obtain meaningful results for absorption spectrum and the RPA
      correlation energy per electron. We implement the approach for silicon
      nanocrystals using real-space grids and find that the overall scaling of the
      algorithm is sublinear with computational time and memory. 

PMID- 25612689
TI  - Deviations from piecewise linearity in the solid-state limit with approximate
      density functionals.
AB  - In exact density functional theory, the total ground-state energy is a series of
      linear segments between integer electron points, a condition known as "piecewise
      linearity." Deviation from this condition is indicative of poor predictive
      capabilities for electronic structure, in particular of ionization energies,
      fundamental gaps, and charge transfer. In this article, we take a new look at the
      deviation from linearity (i.e., curvature) in the solid-state limit by
      considering two different ways of approaching it: a large finite system of
      increasing size and a crystal represented by an increasingly large reference cell
      with periodic boundary conditions. We show that the curvature approaches
      vanishing values in both limits, even for functionals which yield poor
      predictions of electronic structure, and therefore cannot be used as a diagnostic
      or constructive tool in solids. We find that the approach towards zero curvature
      is different in each of the two limits, owing to the presence of a compensating
      background charge in the periodic case. Based on these findings, we present a new
      criterion for functional construction and evaluation, derived from the size
      dependence of the curvature, along with a practical method for evaluating this
      criterion. For large finite systems, we further show that the curvature is
      dominated by the self-interaction of the highest occupied eigenstate. These
      findings are illustrated by computational studies of various solids,
      semiconductor nanocrystals, and long alkane chains. 

PMID- 25612690
TI  - A finite-element visualization of quantum reactive scattering. II.
      Nonadiabaticity on coupled potential energy surfaces.
AB  - This is the second in a series of papers detailing a MATLAB based implementation
      of the finite element method applied to collinear triatomic reactions. Here, we
      extend our previous work to reactions on coupled potential energy surfaces. The
      divergence of the probability current density field associated with the two
      electronically adiabatic states allows us to visualize in a novel way where and
      how nonadiabaticity occurs. A two-dimensional investigation gives additional
      insight into nonadiabaticity beyond standard one-dimensional models. We study the
      F((2)P) + HCl and F((2)P) + H2 reactions as model applications. Our publicly
      available code (http://www2.chem.umd.edu/groups/alexander/FEM) is general and
      easy to use. 

PMID- 25612691
TI  - On the accuracy of coherent modified Redfield theory in simulating excitation
      energy transfer dynamics.
AB  - In this study, we investigate the accuracy of a recently developed coherent
      modified Redfield theory (CMRT) in simulating excitation energy transfer (EET)
      dynamics. The CMRT is a secular non-Markovian quantum master equation that is
      derived by extending the modified Redfield theory to treat coherence dynamics in
      molecular excitonic systems. Herein, we systematically survey the applicability
      of the CMRT in a large EET parameter space through the comparisons of the CMRT
      EET dynamics in a dimer system with the numerically exact results. The results
      confirm that the CMRT exhibits a broad applicable range and allow us to locate
      the specific parameter regimes where CMRT fails to provide adequate results.
      Moreover, we propose an accuracy criterion based on the magnitude of second-order
      perturbation to characterize the applicability of CMRT and show that the
      criterion summarizes all the benchmark results and the physics described by CMRT.
      Finally, we employ the accuracy criterion to quantitatively compare the
      performance of CMRT to that of a small polaron quantum master equation approach.
      The comparison demonstrates the complementary nature of these two methods, and as
      a result, the combination of the two methods provides accurate simulations of EET
      dynamics for the full parameter space investigated in this study. Our results not
      only delicately evaluate the applicability of the CMRT but also reveal new
      physical insights for factors controlling the dynamics of EET that should be
      useful for developing more accurate and efficient methods for simulations of EET
      dynamics in molecular aggregate systems. 

PMID- 25612692
TI  - Accuracy of maximum likelihood estimates of a two-state model in single-molecule
      FRET.
AB  - Photon sequences from single-molecule Forster resonance energy transfer (FRET)
      experiments can be analyzed using a maximum likelihood method. Parameters of the
      underlying kinetic model (FRET efficiencies of the states and transition rates
      between conformational states) are obtained by maximizing the appropriate
      likelihood function. In addition, the errors (uncertainties) of the extracted
      parameters can be obtained from the curvature of the likelihood function at the
      maximum. We study the standard deviations of the parameters of a two-state model
      obtained from photon sequences with recorded colors and arrival times. The
      standard deviations can be obtained analytically in a special case when the FRET
      efficiencies of the states are 0 and 1 and in the limiting cases of fast and slow
      conformational dynamics. These results are compared with the results of numerical
      simulations. The accuracy and, therefore, the ability to predict model parameters
      depend on how fast the transition rates are compared to the photon count rate. In
      the limit of slow transitions, the key parameters that determine the accuracy are
      the number of transitions between the states and the number of independent photon
      sequences. In the fast transition limit, the accuracy is determined by the small
      fraction of photons that are correlated with their neighbors. The relative
      standard deviation of the relaxation rate has a "chevron" shape as a function of
      the transition rate in the log-log scale. The location of the minimum of this
      function dramatically depends on how well the FRET efficiencies of the states are
      separated. 

PMID- 25612693
TI  - Self-consistent continuum solvation for optical absorption of complex molecular
      systems in solution.
AB  - We introduce a new method to compute the optical absorption spectra of complex
      molecular systems in solution, based on the Liouville approach to time-dependent
      density-functional perturbation theory and the revised self-consistent continuum
      solvation model. The former allows one to obtain the absorption spectrum over a
      whole wide frequency range, using a recently proposed Lanczos-based technique, or
      selected excitation energies, using the Casida equation, without having to ever
      compute any unoccupied molecular orbitals. The latter is conceptually similar to
      the polarizable continuum model and offers the further advantages of allowing an
      easy computation of atomic forces via the Hellmann-Feynman theorem and a ready
      implementation in periodic-boundary conditions. The new method has been
      implemented using pseudopotentials and plane-wave basis sets, benchmarked against
      polarizable continuum model calculations on 4-aminophthalimide, alizarin, and
      cyanin and made available through the Quantum ESPRESSO distribution of open
      source codes. 

PMID- 25612694
TI  - Stabilized quasi-Newton optimization of noisy potential energy surfaces.
AB  - Optimizations of atomic positions belong to the most commonly performed tasks in
      electronic structure calculations. Many simulations like global minimum searches
      or characterizations of chemical reactions require performing hundreds or
      thousands of minimizations or saddle computations. To automatize these tasks,
      optimization algorithms must not only be efficient but also very reliable.
      Unfortunately, computational noise in forces and energies is inherent to
      electronic structure codes. This computational noise poses a severe problem to
      the stability of efficient optimization methods like the limited-memory Broyden
      Fletcher-Goldfarb-Shanno algorithm. We here present a technique that allows
      obtaining significant curvature information of noisy potential energy surfaces.
      We use this technique to construct both, a stabilized quasi-Newton minimization
      method and a stabilized quasi-Newton saddle finding approach. We demonstrate with
      the help of benchmarks that both the minimizer and the saddle finding approach
      are superior to comparable existing methods. 

PMID- 25612695
TI  - Fundamental aspects of recoupled pair bonds. I. Recoupled pair bonds in carbon
      and sulfur monofluoride.
AB  - The number of singly occupied orbitals in the ground-state atomic configuration
      of an element defines its nominal valence. For carbon and sulfur, with two singly
      occupied orbitals in their (3)P ground states, the nominal valence is two.
      However, in both cases, it is possible to form more bonds than indicated by the
      nominal valence--up to four bonds for carbon and six bonds for sulfur. In carbon,
      the electrons in the 2s lone pair can participate in bonding, and in sulfur the
      electrons in both the 3p and 3s lone pairs can participate. Carbon 2s and sulfur
      3p recoupled pair bonds are the basis for the tetravalence of carbon and sulfur,
      and 3s recoupled pair bonds enable sulfur to be hexavalent. In this paper, we
      report generalized valence bond as well as more accurate calculations on the
      a(4)Sigma(-) states of CF and SF, which are archetypal examples of molecules that
      possess recoupled pair bonds. These calculations provide insights into the
      fundamental nature of recoupled pair bonds and illustrate the key differences
      between recoupled pair bonds formed with the 2s lone pair of carbon, as a
      representative of the early p-block elements, and recoupled pair bonds formed
      with the 3p lone pair of sulfur, as a representative of the late p-block
      elements.

PMID- 25612696
TI  - Fundamental aspects of recoupled pair bonds. II. Recoupled pair bond dyads in
      carbon and sulfur difluoride.
AB  - Formation of a bond between a second ligand and a molecule with a recoupled pair
      bond results in a recoupled pair bond dyad. We examine the recoupled pair bond
      dyads in the a(3)B1 states of CF2 and SF2, which are formed by the addition of a
      fluorine atom to the a(4)Sigma(-) states of CF and SF, both of which possess
      recoupled pair bonds. The two dyads are very different. In SF2, the second FS-F
      bond is very strong (De = 106.3 kcal/mol), the bond length is much shorter than
      that in the SF(a(4)Sigma(-)) state (1.666 A versus 1.882 A), and the three atoms
      are nearly collinear (thetae = 162.7 degrees ) with only a small barrier to
      linearity (0.4 kcal/mol). In CF2, the second FC-F bond is also very strong (De =
      149.5 kcal/mol), but the bond is only slightly shorter than that in the
      CF(a(4)Sigma(-)) state (1.314 A versus 1.327 A), and the molecule is strongly
      bent (thetae = 119.0 degrees ) with an 80.5 kcal/mol barrier to linearity. The
      a(3)B1 states of CF2 and SF2 illustrate the fundamental differences between
      recoupled pair bond dyads formed from 2s and 3p lone pairs. 

PMID- 25612697
TI  - Non-Markovian Quantum State Diffusion for temperature-dependent linear spectra of
      light harvesting aggregates.
AB  - Non-Markovian Quantum State Diffusion (NMQSD) has turned out to be an efficient
      method to calculate excitonic properties of aggregates composed of organic
      chromophores, taking into account the coupling of electronic transitions to
      vibrational modes of the chromophores. NMQSD is an open quantum system approach
      that incorporates environmental degrees of freedom (the vibrations in our case)
      in a stochastic way. We show in this paper that for linear optical spectra
      (absorption, circular dichroism), no stochastics is needed, even for finite
      temperatures. Thus, the spectra can be obtained by propagating a single
      trajectory. To this end, we map a finite temperature environment to the zero
      temperature case using the so-called thermofield method. The resulting equations
      can then be solved efficiently by standard integrators. 

PMID- 25612698
TI  - Two-component hybrid time-dependent density functional theory within the Tamm
      Dancoff approximation.
AB  - We report the implementation of a two-component variant of time-dependent density
      functional theory (TDDFT) for hybrid functionals that accounts for spin-orbit
      effects within the Tamm-Dancoff approximation (TDA) for closed-shell systems. The
      influence of the admixture of Hartree-Fock exchange on excitation energies is
      investigated for several atoms and diatomic molecules by comparison to numbers
      for pure density functionals obtained previously [M. Kuhn and F. Weigend, J.
      Chem. Theory Comput. 9, 5341 (2013)]. It is further related to changes upon
      switching to the local density approximation or using the full TDDFT formalism
      instead of TDA. Efficiency is demonstrated for a comparably large system,
      Ir(ppy)3 (61 atoms, 1501 basis functions, lowest 10 excited states), which is a
      prototype molecule for organic light-emitting diodes, due to its "spin-forbidden"
      triplet-singlet transition. 

PMID- 25612699
TI  - Arbitrary order permanent Cartesian multipolar electrostatic interactions.
AB  - Recently, there has been a concerted effort to implement advanced classical
      potential energy surfaces by adding higher order multipoles to fixed point charge
      electrostatics in a bid to increase the accuracy of simulations of condensed
      phase systems. One major hurdle is the unwieldy nature of the expressions which
      in part has limited developers mostly to including only dipoles and quadrupoles.
      In this paper, we present a generalization of the Cartesian formulation of
      electrostatic multipolar interactions that enables the specification of an
      arbitrary order of multipoles. Specifically, we derive formulas for arbitrary
      order implementation of the particle mesh Ewald method and give a closed form
      formula for the stress tensor in the reciprocal space. In addition, we provide
      recurrence relations for common electrostatic potentials employed in molecular
      simulations, which allows for the generalization to arbitrary order and
      guarantees a computational cost that scales as O(p(3)) for Cartesian multipole
      interactions of order p. 

PMID- 25612700
TI  - Adaptive hybrid simulations for multiscale stochastic reaction networks.
AB  - The probability distribution describing the state of a Stochastic Reaction
      Network (SRN) evolves according to the Chemical Master Equation (CME). It is
      common to estimate its solution using Monte Carlo methods such as the Stochastic
      Simulation Algorithm (SSA). In many cases, these simulations can take an
      impractical amount of computational time. Therefore, many methods have been
      developed that approximate sample paths of the underlying stochastic process and
      estimate the solution of the CME. A prominent class of these methods include
      hybrid methods that partition the set of species and the set of reactions into
      discrete and continuous subsets. Such a partition separates the dynamics into a
      discrete and a continuous part. Simulating such a stochastic process can be
      computationally much easier than simulating the exact discrete stochastic process
      with SSA. Moreover, the quasi-stationary assumption to approximate the dynamics
      of fast subnetworks can be applied for certain classes of networks. However, as
      the dynamics of a SRN evolves, these partitions may have to be adapted during the
      simulation. We develop a hybrid method that approximates the solution of a CME by
      automatically partitioning the reactions and species sets into discrete and
      continuous components and applying the quasi-stationary assumption on
      identifiable fast subnetworks. Our method does not require any user intervention
      and it adapts to exploit the changing timescale separation between reactions
      and/or changing magnitudes of copy-numbers of constituent species. We demonstrate
      the efficiency of the proposed method by considering examples from systems
      biology and showing that very good approximations to the exact probability
      distributions can be achieved in significantly less computational time. This is
      especially the case for systems with oscillatory dynamics, where the system
      dynamics change considerably throughout the time-period of interest. 

PMID- 25612702
TI  - Time-dependent non-equilibrium dielectric response in QM/continuum approaches.
AB  - The Polarizable Continuum Models (PCMs) are some of the most inexpensive yet
      successful methods for including the effects of solvation in quantum-mechanical
      calculations of molecular systems. However, when applied to the electronic
      excitation process, these methods are restricted to dichotomously assuming either
      that the solvent has completely equilibrated with the excited solute charge
      density (infinite-time limit), or that it retains the configuration that was in
      equilibrium with the solute prior to excitation (zero-time limit). This renders
      the traditional PCMs inappropriate for resolving time-dependent solvent effects
      on non-equilibrium solute electron dynamics like those implicated in the instants
      following photoexcitation of a solvated molecular species. To extend the existing
      methods to this non-equilibrium regime, we herein derive and apply a new
      formalism for a general time-dependent continuum embedding method designed to be
      propagated alongside the solute's electronic degrees of freedom in the time
      domain. Given the frequency-dependent dielectric constant of the solvent, an
      equation of motion for the dielectric polarization is derived within the PCM
      framework and numerically integrated simultaneously with the time-dependent
      Hartree fock/density functional theory equations. Results for small molecular
      systems show the anticipated dipole quenching and electronic state
      dephasing/relaxation resulting from out-of-phase charge fluctuations in the
      dielectric and embedded quantum system. 

PMID- 25612701
TI  - Molecular quantum mechanical gradients within the polarizable embedding approach-
      application to the internal vibrational Stark shift of acetophenone.
AB  - We present an implementation of analytical quantum mechanical molecular gradients
      within the polarizable embedding (PE) model to allow for efficient geometry
      optimizations and vibrational analysis of molecules embedded in large,
      geometrically frozen environments. We consider a variational ansatz for the
      quantum region, covering (multiconfigurational) self-consistent-field and Kohn
      Sham density functional theory. As the first application of the implementation,
      we consider the internal vibrational Stark effect of the C=O group of
      acetophenone in different solvents and derive its vibrational linear Stark tuning
      rate using harmonic frequencies calculated from analytical gradients and computed
      local electric fields. Comparisons to PE calculations employing an enlarged
      quantum region as well as to a non-polarizable embedding scheme show that the
      inclusion of mutual polarization between acetophenone and water is essential in
      order to capture the structural modifications and the associated frequency shifts
      observed in water. For more apolar solvents, a proper description of dispersion
      and exchange-repulsion becomes increasingly important, and the quality of the
      optimized structures relies to a larger extent on the quality of the Lennard
      Jones parameters. 

PMID- 25612703
TI  - Low energy electron attachment to cyanamide (NH2CN).
AB  - Cyanamide (NH2CN) is a molecule relevant for interstellar chemistry and the
      chemical evolution of life. In the present investigation, dissociative electron
      attachment to NH2CN has been studied in a crossed electron-molecular beams
      experiment in the electron energy range from about 0 eV to 14 eV. The following
      anionic species were detected: NHCN(-), NCN(-), CN(-), NH2(-), NH(-), and CH2(-).
      The anion formation proceeds within two broad electron energy regions, one
      between about 0.5 and 4.5 eV and a second between 4.5 and 12 eV. A discussion of
      possible reaction channels for all measured negative ions is provided. The
      experimental results are compared with calculations of the thermochemical
      thresholds of the anions observed. For the dehydrogenated parent anion, we
      explain the deviation between the experimental appearance energy of the anion
      with the calculated corresponding reaction threshold by electron attachment to
      the isomeric form of NH2CN--carbodiimide.

PMID- 25612704
TI  - Theoretical reproduction of the Q-band absorption spectrum of free-base chlorin.
AB  - The computational results of the features observed in the room-temperature Q-band
      absorption spectrum of free-base chlorin (H2Ch) are presented. The vibrational
      structures of the first and second excited singlet states were calculated based
      on a harmonic approximation using density functional theory and its time
      dependent extension within the Franck-Condon and Herzberg-Teller approaches. The
      outcome allowed to identify the experimental bands and to assign them to the
      specific vibrational transitions. A very good agreement between the simulated and
      measured wavelengths and their relative intensities provided the opportunity to
      predict the origin of the S0 -> S2 transition which could not be determined
      experimentally. 

PMID- 25612705
TI  - Theoretical investigation of stabilities and optical properties of Si12C12
      clusters.
AB  - By sorting through hundreds of globally stable Si12C12 isomers using a potential
      surface search and using simulated annealing, we have identified low-energy
      structures. Unlike isomers knit together by Si-C bonds, the lowest energy isomers
      have segregated carbon and silicon regions that maximize stronger C-C bonding.
      Positing that charge separation between the carbon and silicon regions would
      produce interesting optical absorption in these cluster molecules, we used time
      dependent density functional theory to compare the calculated optical properties
      of four isomers representing structural classes having different types of silicon
      and carbon segregation regions. Absorptions involving charge transfer between
      segregated carbon and silicon regions produce lower excitation energies than do
      structures having alternating Si-C bonding for which frontier orbital charge
      transfer is exclusively from separated carbon atoms to silicon atoms. The most
      stable Si12C12 isomer at temperatures below 1100 K is unique as regards its high
      symmetry and large optical oscillator strength in the visible blue. Its high
      energy and low-energy visible transitions (1.15 eV and 2.56 eV) are nearly pure
      one-electron silicon-to-carbon transitions, while an intermediate energy
      transition (1.28 eV) is a nearly pure carbon-to-silicon one-electron charge
      transfer. 

PMID- 25612707
TI  - Second virial coefficient of a generalized Lennard-Jones potential.
AB  - We present an exact analytical solution for the second virial coefficient of a
      generalized Lennard-Jones type of pair potential model. The potential can be
      reduced to the Lennard-Jones, hard-sphere, and sticky hard-sphere models by
      tuning the potential parameters corresponding to the width and depth of the well.
      Thus, the second virial solution can also regain the aforementioned cases.
      Moreover, the obtained expression strongly resembles the one corresponding to the
      Kihara potential. In fact, the Fk functions are the same. Furthermore, for these
      functions, the complete expansions at low and high temperature are given.
      Additionally, we propose an alternative stickiness parameter based on the
      obtained second virial coefficient. 

PMID- 25612706
TI  - Systematic theoretical investigation of the zero-field splitting in Gd(III)
      complexes: wave function and density functional approaches.
AB  - The zero-field splitting (ZFS) of the electronic ground state in paramagnetic
      ions is a sensitive probe of the variations in the electronic and molecular
      structure with an impact on fields ranging from fundamental physical chemistry to
      medical applications. A detailed analysis of the ZFS in a series of symmetric
      Gd(III) complexes is presented in order to establish the applicability and
      accuracy of computational methods using multiconfigurational complete-active
      space self-consistent field wave functions and of density functional theory
      calculations. The various computational schemes are then applied to larger
      complexes Gd(III)DOTA(H2O)(-), Gd(III)DTPA(H2O)(2-), and Gd(III)(H2O)8(3+) in
      order to analyze how the theoretical results compare to experimentally derived
      parameters. In contrast to approximations based on density functional theory, the
      multiconfigurational methods produce results for the ZFS of Gd(III) complexes on
      the correct order of magnitude.

PMID- 25612708
TI  - Hartree-Fock calculation of the differential photoionization cross sections of
      small Li clusters.
AB  - Cross sections and angular distribution parameters for the single-photon
      ionization of all electron orbitals of Li2-8 are systematically computed in a
      broad interval of the photoelectron kinetic energies for the energetically most
      stable geometry of each cluster. Calculations of the partial photoelectron
      continuum waves in clusters are carried out by the single center method within
      the Hartree-Fock approximation. We study photoionization cross sections per one
      electron and analyze in some details general trends in the photoionization of
      inner and outer shells with respect to the size and geometry of a cluster. The
      present differential cross sections computed for Li2 are in a good agreement with
      the available theoretical data, whereas those computed for Li3-8 clusters can be
      considered as theoretical predictions. 

PMID- 25612710
TI  - Theoretical study on the ground state of the polar alkali-metal-barium molecules:
      potential energy curve and permanent dipole moment.
AB  - In this paper, we systematically investigate the electronic structure for the
      (2)Sigma(+) ground state of the polar alkali-metal-alkaline-earth-metal molecules
      BaAlk (Alk = Li, Na, K, Rb, and Cs). Potential energy curves and permanent dipole
      moments (PDMs) are determined using power quantum chemistry complete active space
      self-consistent field and multi-reference configuration interaction methods.
      Basic spectroscopic constants are derived from ro-vibrational bound state
      calculation. From the calculations, it is shown that BaK, BaRb, and BaCs
      molecules have moderate values of PDM at the equilibrium bond distance (BaK:1.62
      D, BaRb:3.32 D, and BaCs:4.02 D). Besides, the equilibrium bond length (4.93 A
      and 5.19 A) and dissociation energy (0.1825 eV and 0.1817 eV) for the BaRb and
      BaCs are also obtained. 

PMID- 25612709
TI  - Tetrel, chalcogen, and CH??O hydrogen bonds in complexes pairing carbonyl
      containing molecules with 1, 2, and 3 molecules of CO2.
AB  - The complexes formed by H2CO, CH3CHO, and (CH3)2CO with 1, 2, and 3 molecules of
      CO2 are studied by ab initio calculations. Three different types of heterodimers
      are observed, most containing a tetrel bond to the C atom of CO2, and some
      supplemented by a CH??O H-bond. One type of heterodimer is stabilized by an anti
      parallel arrangement of the C=O bonds of the two molecules. The binding energies
      are enhanced by methyl substitution on the carbonyl, and vary between 2.4 and 3.5
      kcal/mol. Natural bond orbital analysis identifies a prime source of interaction
      as charge transfer into the pi*(CO) antibonding orbital. Heterotrimers and
      tetramers carry over many of the geometrical and bonding features of the binary
      complexes, but also introduce O??O chalcogen bonds. These larger complexes
      exhibit only small amounts of cooperativity. 

PMID- 25612711
TI  - Differential and integral cross sections in OH(X) + Xe collisions.
AB  - Differential cross sections (DCSs) for inelastic collisions of OH(X) with Xe have
      been measured at a collision energy of 483 cm(-1). The hydroxyl (OH) radicals
      were initially prepared in the X(2)Pi3/2 (v = 0, j = 1.5, f) level using the
      hexapole electric field selection method. Products were detected state
      selectively by [2 + 1] resonance-enhanced multiphoton ionization of OH, combined
      with velocity-map imaging. Integral cross sections in OH(X) + Xe at a collision
      energy of 490 cm(-1) were also measured by laser-induced fluorescence. The
      results are compared with exact close-coupling quantum mechanical scattering
      calculations on the only available ab initio potential energy surface (PES). The
      agreement between experimental and theoretical results is generally very
      satisfactory. This highlights the ability of such measurements to test the
      available PES for such a benchmark open-shell system. The agreement between
      experiment and theory for DCSs is less satisfactory at low scattering angles, and
      possible reasons for this disagreement are discussed. Finally, theoretical
      calculations of OH(X) + He DCSs have been obtained at various collision energies
      and are compared with those of OH(X) + Xe. The role of the reduced mass in the
      DCSs and partial cross sections is also examined. 

PMID- 25612712
TI  - Optical absorption spectra of palladium doped gold cluster cations.
AB  - Photoabsorption spectra of gas phase Au(n)(+) and Au(n-1)Pd(+) (13 <= n <= 20)
      clusters were measured using mass spectrometric recording of wavelength dependent
      Xe messenger atom photodetachment in the 1.9-3.4 eV photon energy range. Pure
      cationic gold clusters consisting of 15, 17, and 20 atoms have a higher
      integrated optical absorption cross section than the neighboring sizes. It is
      shown that the total optical absorption cross section increases with size and
      that palladium doping strongly reduces this cross section for all investigated
      sizes and in particular for n = 14-17 and 20. The largest reduction of optical
      absorption upon Pd doping is observed for n = 15.

PMID- 25612713
TI  - Interaction of the NO 3ppi (C (2)Pi) Rydberg state with RG (RG = Ne, Kr, and Xe):
      potential energy surfaces and spectroscopy.
AB  - We present new potential energy surfaces for the interaction of NO(C (2)Pi) with
      each of Ne, Kr, and Xe. The potential energy surfaces have been calculated using
      second order Moller-Plesset perturbation theory, exploiting a procedure to
      converge the reference Hartree-Fock wavefunction for the excited states: the
      maximum overlap method. The bound rovibrational states obtained from the surfaces
      are used to simulate the electronic spectra and their appearance is in good
      agreement with available (2+1) REMPI spectra. We discuss the assignment and
      appearance of these spectra, comparing to that of NO-Ar. 

PMID- 25612714
TI  - Isobaric first-principles molecular dynamics of liquid water with nonlocal van
      der Waals interactions.
AB  - We investigate the structural properties of liquid water at near ambient
      conditions using first-principles molecular dynamics simulations based on a
      semilocal density functional augmented with nonlocal van der Waals interactions.
      The adopted scheme offers the advantage of simulating liquid water at essentially
      the same computational cost of standard semilocal functionals. Applied to the
      water dimer and to ice Ih, we find that the hydrogen-bond energy is only slightly
      enhanced compared to a standard semilocal functional. We simulate liquid water
      through molecular dynamics in the NpH statistical ensemble allowing for
      fluctuations of the system density. The structure of the liquid departs from that
      found with a semilocal functional leading to more compact structural
      arrangements. This indicates that the directionality of the hydrogen-bond
      interaction has a diminished role as compared to the overall attractions, as
      expected when dispersion interactions are accounted for. This is substantiated
      through a detailed analysis comprising the study of the partial radial
      distribution functions, various local order indices, the hydrogen-bond network,
      and the selfdiffusion coefficient. The explicit treatment of the van der Waals
      interactions leads to an overall improved description of liquid water. 

PMID- 25612715
TI  - Effects of the surroundings and conformerisation of n-dodecane molecules on
      evaporation/condensation processes.
AB  - The evaporation/condensation coefficient (beta) and the evaporation rate (gamma)
      for n-dodecane vs. temperature, gas pressure, gas and liquid density, and
      solvation effects at a droplet surface are analysed using quantum chemical
      density functional theory calculations of several ensembles of conformers of n
      dodecane molecules in the gas phase (hybrid functional omegaB97X-D with the cc
      pVTZ and cc-pVDZ basis sets) and in liquid phase (solvation method: SMD/omegaB97X
      D). It is shown that beta depends more strongly on a number of neighbouring
      molecules interacting with an evaporating molecule at a droplet surface (this
      number is estimated through changes in the surface Gibbs free energy of
      solvation) than on pressure in the gas phase or conformerisation and cross
      conformerisation of molecules in both phases. Thus, temperature and the
      surrounding effects at droplet surfaces are the dominant factors affecting the
      values of beta for n-dodecane molecules. These values are shown to be similar (at
      reduced temperatures T/Tc < 0.8) or slightly larger (at T/Tc > 0.8) than the
      values of beta calculated by the molecular dynamics force fields (MD FF) methods.
      This endorses the reliability of the previously developed classical approach to
      estimation of beta by the MD FF methods, except at temperatures close to the
      critical temperature. 

PMID- 25612716
TI  - Change of translational-rotational coupling in liquids revealed by field-cycling
      1H NMR.
AB  - Applying the field-cycling nuclear magnetic resonance technique, the frequency
      dependence of the (1)H spin-lattice relaxation rate, R1omega=T1(-1)omega, is
      measured for propylene glycol (PG) which is increasingly diluted with deuterated
      chloroform. A frequency range of 10 kHz-20 MHz and a broad temperature interval
      from 220 to about 100 K are covered. The results are compared to those of
      experiments, where glycerol and o-terphenyl are diluted with their deuterated
      counter-part. Reflecting intra- as well as intermolecular relaxation, the
      dispersion curves R1omega,x (x denotes mole fraction PG) allow to extract the
      rotational time constant taurot(T, x) and the self-diffusion coefficient D(T, x)
      in a single experiment. The Stokes-Einstein-Debye (SED) relation is tested in
      terms of the quantity D(T, x) taurot(T, x) which provides a measure of an
      effective hydrodynamic radius or equivalently of the spectral separation of the
      translational and the rotational relaxation contribution. In contrast to o
      terphenyl, glycerol and PG show a spectral separation much larger than suggested
      by the SED relation. In the case of PG/chloroform mixtures, not only an
      acceleration of the PG dynamics is observed with increasing dilution but also the
      spectral separation of rotational and translational relaxation contributions
      continuously decreases. Finally, following a behavior similar to that of o
      terphenyl already at about x = 0.6; i.e., while D(T, x) taurot(T, x) in the
      mixture is essentially temperature independent, it strongly increases with x
      signaling thus a change of translational-rotational coupling. This directly
      reflects the dissolution of the hydrogen-bond network and thus a change of
      solution structure.

PMID- 25612717
TI  - Range effect on percolation threshold and structural properties for short-range
      attractive spheres.
AB  - Percolation or aggregation in colloidal system is important in many fields of
      science and technology. Using molecular dynamics simulations, we study the
      percolation behavior for systems consisting of spheres interacting with short
      range square-well (SRSW) which mimic colloidal particles, with different
      interaction ranges. We specifically focus on how the interaction range affects
      the percolation thresholds in the supercritical region. We find that the contact
      percolation boundaries are strongly dependent on the interaction ranges of SRSW,
      especially away from the liquid-liquid critical point. However, varying the
      interaction ranges of SRSW does not affect much the structure along percolation
      boundaries especially for low packing fractions. For instance, along the
      percolation boundary, distributions of coordination number show convergence, and
      distributions of cluster size are universal for different interaction ranges
      considered. In addition, either the bond percolation boundaries or isolines of
      average bond coordination number collapse to those for Baxter sticky model on
      phase diagram, which confirms the extended law of corresponding states. 

PMID- 25612718
TI  - Density relaxation and particle motion characteristics in a non-ionic deep
      eutectic solvent (acetamide + urea): time-resolved fluorescence measurements and
      all-atom molecular dynamics simulations.
AB  - Temperature dependent relaxation dynamics, particle motion characteristics, and
      heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide
      (CH3CONH2) and urea (NH2CONH2) have been investigated by employing time-resolved
      fluorescence measurements and all-atom molecular dynamics simulations. Three
      different compositions (f) for the mixture [fCH3CONH2 + (1 - f)NH2CONH2] have
      been studied in a temperature range of 328-353 K which is ~120-145 K above the
      measured glass transition temperatures (~207 K) of these DESs but much lower than
      the individual melting temperature of either of the constituents. Steady state
      fluorescence emission measurements using probe solutes with sharply different
      lifetimes do not indicate any dependence on excitation wavelength in these
      metastable molten systems. Time-resolved fluorescence anisotropy measurements
      reveal near-hydrodynamic coupling between medium viscosity and rotation of a
      dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to
      be detected by the time-resolution (~70 ps) employed, suggesting extremely rapid
      medium polarization relaxation. All-atom simulations reveal Gaussian distribution
      for particle displacements and van Hove correlations, and significant overlap
      between non-Gaussian (alpha2) and new non-Gaussian (gamma) heterogeneity
      parameters. In addition, no stretched exponential relaxations have been detected
      in the simulated wavenumber dependent acetamide dynamic structure factors. All
      these results are in sharp contrast to earlier observations for ionic deep
      eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and
      suggest a fundamental difference in interaction and dynamics between ionic and
      non-ionic deep eutectic solvent systems. 

PMID- 25612719
TI  - Space- and time-dependent quantum dynamics of spatially indirect excitons in
      semiconductor heterostructures.
AB  - We study the unitary propagation of a two-particle one-dimensional Schrodinger
      equation by means of the Split-Step Fourier method, to study the coherent
      evolution of a spatially indirect exciton (IX) in semiconductor heterostructures.
      The mutual Coulomb interaction of the electron-hole pair and the electrostatic
      potentials generated by external gates and acting on the two particles separately
      are taken into account exactly in the two-particle dynamics. As relevant
      examples, step/downhill and barrier/well potential profiles are considered. The
      space- and time-dependent evolutions during the scattering event as well as the
      asymptotic time behavior are analyzed. For typical parameters of GaAs-based
      devices, the transmission or reflection of the pair turns out to be a complex two
      particle process, due to comparable and competing Coulomb, electrostatic, and
      kinetic energy scales. Depending on the intensity and anisotropy of the
      scattering potentials, the quantum evolution may result in excitation of the IX
      internal degrees of freedom, dissociation of the pair, or transmission in small
      periodic IX wavepackets due to dwelling of one particle in the barrier region. We
      discuss the occurrence of each process in the full parameter space of the
      scattering potentials and the relevance of our results for current excitronic
      technologies. 

PMID- 25612720
TI  - Pressure-induced transformations of onion-like carbon nanospheres up to 48 GPa.
AB  - Raman spectra of onion-like carbon nanospheres (OCNSs) have been studied under
      pressure up to 48 GPa. A transformation related to a change from sp(2) to sp(3)
      bonding of carbons in OCNSs was observed at pressures above 20 GPa. The Raman
      spectra exhibit some vibrational features similar to those of the theoretically
      proposed Z-carbon phase of cold-compressed graphite, while the transition
      pressure is obviously higher than that for graphite. In contrast to the
      transformations in compressed graphite, interlayer bonds are formed on the
      nanoscale between buckled layers in OCNSs under pressure due to the concentric
      configuration, and sp(2)-sp(3) conversion is incomplete even up to 48 GPa. This
      is confirmed by TEM observations on the decompressed samples. Moreover, the onion
      like carbon structure is extremely stable and can be recovered even after a
      compression cycle to 48 GPa. This high stability, beyond that of other sp(2)
      carbon materials, is related to the unique onion-like configuration and to the
      interlayer bonding. The transformed material should have excellent mechanical
      properties so that it can sustain very high pressure. 

PMID- 25612721
TI  - Effect of the hydroaffinity and topology of pore walls on the structure and
      dynamics of confined water.
AB  - We perform molecular dynamics simulations to observe the structure and dynamics
      of SPC/E water in amorphous silica pores and amorphous ice pores with radii
      slightly larger than 10 A. In addition to atomically rough pores, we construct
      completely smooth pores such that the potential felt at a given distance from the
      pore wall is an averaged atomic potential. As compared to rough walls, smooth
      walls induce stronger distortions of water structure for both silica and ice
      confinements. On the other hand, unlike the smooth pores, the rough pores
      strongly slow down water dynamics at the pore wall. The slowdown vanishes when
      reducing the atomic charges in the wall, i.e., when varying the hydroaffinity,
      while keeping the surface topology, indicating that it is not a geometric effect.
      Rather, it is due to the fact that the wall atoms provide a static energy
      landscape along the surface, e.g., fixed anchor-points for hydrogen bonds, to
      which the water molecules need to adapt, blocking channels for structural
      rearrangement. In the smooth pores, water dynamics can be faster than in the bulk
      liquid not only at the pore wall but also in the pore center. Changes in the
      tetrahedral order rather than in the local density are identified as the main
      cause for this change of the dynamical behavior in the center of smooth pores. 

PMID- 25612722
TI  - Wetting behavior of nonpolar nanotubes in simple dipolar liquids for varying
      nanotube diameter and solute-solvent interactions.
AB  - Atomistic simulations of model nonpolar nanotubes in a Stockmayer liquid are
      carried out for varying nanotube diameter and nanotube-solvent interactions to
      investigate solvophobic interactions in generic dipolar solvents. We have
      considered model armchair type single-walled nonpolar nanotubes with increasing
      radii from (5,5) to (12,12). The interactions between solute and solvent
      molecules are modeled by the well-known Lennard-Jones and repulsive Weeks
      Chandler-Andersen potentials. We have investigated the density profiles and
      microscopic arrangement of Stockmayer molecules, orientational profiles of their
      dipole vectors, time dependence of their occupation, and also the translational
      and rotational motion of solvent molecules in confined environments of the
      cylindrical nanopores and also in their external peripheral regions. The present
      results of structural and dynamical properties of Stockmayer molecules inside and
      near atomistically rough nonpolar surfaces including their wetting and dewetting
      behavior for varying interactions provide a more generic picture of solvophobic
      effects experienced by simple dipolar liquids without any specific interactions
      such as hydrogen bonds. 

PMID- 25612723
TI  - Adhesion of nanoparticles to polymer brushes studied with the ghost tweezers
      method.
AB  - Mechanisms of interactions between nanoparticles (NPs) and polymer brushes (PBs)
      are explored using dissipative particle dynamics simulations and an original
      "ghost tweezers" method that emulates lab experiments performed with optical or
      magnetic tweezers. The ghost tweezers method is employed to calculate the free
      energy of adhesion. Ghost tweezers represents a virtual harmonic potential, which
      tethers NP with a spring to a given anchor point. The average spring force
      represents the effective force of NP-PB interaction as a function of the NP
      coordinate. The free energy landscape of NP-PB interactions is calculated as the
      mechanical work needed to transfer NP from the solvent bulk to a particular
      distance from the substrate surface. With this technique, we explore the adhesion
      of bare and ligand-functionalized spherical NPs to polyisoprene natural rubber
      brush in acetone-benzene binary solvent. We examine two basic mechanisms of NP-PB
      interactions, NP adhesion at PB exterior and NP immersion into PB, which are
      governed by interplay between entropic repulsive forces and enthalpic attractive
      forces caused by polymer adsorption at the NP surface and ligand adsorption at
      the substrate. The relative free energies of the equilibrium adhesion states and
      the potential barriers separating these states are calculated at varying grafting
      density, NP size, and solvent composition. 

PMID- 25612724
TI  - Local order of liquid water at metallic electrode surfaces.
AB  - We study the structure and dynamics of liquid water in contact with Pd and Au
      (111) surfaces using ab initio molecular dynamics simulations with and without
      van der Waals interactions. Our results show that the structure of water at the
      interface of these two metals is very different. For Pd, we observe the formation
      of two different domains of preferred orientations, with opposite net interfacial
      dipoles. One of these two domains has a large degree of in-plane hexagonal order.
      For Au, a single domain exists with no in-plane order. For both metals, the
      structure of liquid water at the interface is strongly dependent on the use of
      dispersion forces. The origin of the structural domains observed in Pd is
      associated to the interplay between water/water and water/metal interactions.
      This effect is strongly dependent on the charge transfer that occurs at the
      interface and which is not modeled by current state of the art semi-empirical
      force fields. 

PMID- 25612725
TI  - Effect of gold subsurface layer on the surface activity and segregation in
      Pt/Au/Pt3M (where M = 3d transition metals) alloy catalyst from first-principles.
AB  - The effect of a subsurface hetero layer (thin gold) on the activity and stability
      of Pt skin surface in Pt3M system (M = 3d transition metals) is investigated
      using the spin-polarized density functional theory calculation. First, we find
      that the heterometallic interaction between the Pt skin surface and the gold
      subsurface in Pt/Au/Pt3M system can significantly modify the electronic structure
      of the Pt skin surface. In particular, the local density of states projected onto
      the d states of Pt skin surface near the Fermi level is drastically decreased
      compared to the Pt/Pt/Pt3M case, leading to the reduction of the oxygen binding
      strength of the Pt skin surface. This modification is related to the increase of
      surface charge polarization of outmost Pt skin atoms by the electron transfer
      from the gold subsurface atoms. Furthermore, a subsurface gold layer is found to
      cast the energetic barrier to the segregation loss of metal atoms from the bulk
      (inside) region, which can enhance the durability of Pt3M based catalytic system
      in oxygen reduction condition at fuel cell devices. This study highlights that a
      gold subsurface hetero layer can provide an additional mean to tune the surface
      activity toward oxygen species and in turn the oxygen reduction reaction, where
      the utilization of geometric strain already reaches its practical limit. 

PMID- 25612726
TI  - Wetting of prototypical one- and two-dimensional systems: thermodynamics and
      density functional theory.
AB  - Consider a two-dimensional capped capillary pore formed by capping two parallel
      planar walls with a third wall orthogonal to the two planar walls. This system
      reduces to a slit pore sufficiently far from the capping wall and to a single
      planar wall when the side walls are far apart. Not surprisingly, wetting of
      capped capillaries is related to wetting of slit pores and planar walls. For
      example, the wetting temperature of the capped capillary provides the boundary
      between first-order and continuous transitions to condensation. We present a
      numerical investigation of adsorption in capped capillaries of mesoscopic widths
      based on density functional theory. The fluid-fluid and fluid-substrate
      interactions are given by the pairwise Lennard-Jones potential. We also perform a
      parametric study of wetting in capped capillaries by a liquid phase by varying
      the applied chemical potential, temperature, and pore width. This allows us to
      construct surface phase diagrams and investigate the complicated interplay of
      wetting mechanisms specific to each system, in particular, the dependence of
      capillary wetting temperature on the pore width. 

PMID- 25612727
TI  - Effects of rotational symmetry breaking in polymer-coated nanopores.
AB  - The statistical theory of polymers tethered around the inner surface of a
      cylindrical channel has traditionally employed the assumption that the
      equilibrium density of the polymers is independent of the azimuthal coordinate.
      However, simulations have shown that this rotational symmetry can be broken when
      there are attractive interactions between the polymers. We investigate the phases
      that emerge in these circumstances, and we quantify the effect of the symmetry
      assumption on the phase behavior of the system. In the absence of this
      assumption, one can observe large differences in the equilibrium densities
      between the rotationally symmetric case and the non-rotationally symmetric case.
      A simple analytical model is developed that illustrates the driving thermodynamic
      forces responsible for this symmetry breaking. Our results have implications for
      the current understanding of the behavior of polymers in cylindrical nanopores. 

PMID- 25612728
TI  - Theory of melt polyelectrolyte blends and block copolymers: phase behavior,
      surface tension, and microphase periodicity.
AB  - Polymer mixtures such as blends or block copolymers are of great interest in
      energy applications and functional materials, and often, one or more of these
      species contain charges. The traditional fashion in which such materials are
      studied uses Self-Consistent Field Theory (SCFT) methods that incorporate
      electrostatics using Poisson-Boltzmann (PB) theory. We adapt a new and rigorous
      approach that does not rely on the mean-field assumptions inherent in the PB
      theory and instead uses Liquid State (LS) integral equation theory to articulate
      charge correlations that are completely neglected in PB. We use this theory to
      calculate phase diagrams for both blends and block copolyelectrolytes using SCFT
      LS and demonstrate how their phase behavior is highly dependent on chain length,
      charge fraction, charge size, and the strength of Coulombic interactions. Beyond
      providing phase behavior of blends and block copolyelectrolytes, we can use this
      theory to investigate the interfacial properties such as surface tension and
      block copolyelectrolyte lamellar spacing. Lamellar spacing provides a way to
      directly compare the SCFT-LS theory to the results of experiments. SCFT-LS will
      provide conceptual and mathematical clarification of the role of charge
      correlations in these systems and aid in the design of materials based on charge
      polymers. 

PMID- 25612729
TI  - DNA denaturation bubbles: free-energy landscape and nucleation/closure rates.
AB  - The issue of the nucleation and slow closure mechanisms of non-superhelical
      stress-induced denaturation bubbles in DNA is tackled using coarse-grained
      MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where
      the double helix is made of two interacting bead-spring rotating strands with a
      prescribed torsional modulus in the duplex state. We demonstrate that timescales
      for the nucleation (respectively, closure) of an approximately 10 base-pair
      bubble, in agreement with experiments, are associated with the crossing of a free
      energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T.
      MetaDynamics allows us to reconstruct accurately the free-energy landscape, to
      show that the free-energy barriers come from the difference in torsional energy
      between the bubble and duplex states, and thus to highlight the limiting step, a
      collective twisting, that controls the nucleation/closure mechanism, and to
      access opening time scales on the millisecond range. Contrary to small breathing
      bubbles, those more than 4 base-pair bubbles are of biological relevance, for
      example, when a pre-existing state of denaturation is required by specific DNA
      binding proteins. 

PMID- 25612730
TI  - Structure and osmotic pressure of ionic microgel dispersions.
AB  - We investigate structural and thermodynamic properties of aqueous dispersions of
      ionic microgels--soft colloidal gel particles that exhibit unusual phase
      behavior. Starting from a coarse-grained model of microgel macroions as charged
      spheres that are permeable to microions, we perform simulations and theoretical
      calculations using two complementary implementations of Poisson-Boltzmann (PB)
      theory. Within a one-component model, based on a linear-screening approximation
      for effective electrostatic pair interactions, we perform molecular dynamics
      simulations to compute macroion-macroion radial distribution functions, static
      structure factors, and macroion contributions to the osmotic pressure. For the
      same model, using a variational approximation for the free energy, we compute
      both macroion and microion contributions to the osmotic pressure. Within a
      spherical cell model, which neglects macroion correlations, we solve the
      nonlinear PB equation to compute microion distributions and osmotic pressures. By
      comparing the one-component and cell model implementations of PB theory, we
      demonstrate that the linear-screening approximation is valid for moderately
      charged microgels. By further comparing cell model predictions with simulation
      data for osmotic pressure, we chart the cell model's limits in predicting osmotic
      pressures of salty dispersions.

PMID- 25612731
TI  - Probing the folded state and mechanical unfolding pathways of T4 lysozyme using
      all-atom and coarse-grained molecular simulation.
AB  - The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of
      an N-terminal and a C-domain domain, which was extensively studied to understand
      the folding/unfolding mechanism of modular proteins. To offer detailed structural
      and dynamic insights to the folded-state stability and the mechanical unfolding
      behaviors of T4L, we have performed extensive equilibrium and steered molecular
      dynamics simulations of both the wild-type (WT) and a circular permutation (CP)
      variant of T4L using all-atom and coarse-grained force fields. Our all-atom and
      coarse-grained simulations of the folded state have consistently found greater
      stability of the C-domain than the N-domain in isolation, which is in agreement
      with past thermostatic studies of T4L. While the all-atom simulation cannot fully
      explain the mechanical unfolding behaviors of the WT and the CP variant observed
      in an optical tweezers study, the coarse-grained simulations based on the Go
      model or a modified elastic network model (mENM) are in qualitative agreement
      with the experimental finding of greater unfolding cooperativity in the WT than
      the CP variant. Interestingly, the two coarse-grained models predict different
      structural mechanisms for the observed change in cooperativity between the WT and
      the CP variant--while the Go model predicts minor modification of the unfolding
      pathways by circular permutation (i.e., preserving the general order that the N
      domain unfolds before the C-domain), the mENM predicts a dramatic change in
      unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and
      the CP variant). Based on our simulations, we have analyzed the limitations of
      and the key differences between these models and offered testable predictions for
      future experiments to resolve the structural mechanism for cooperative
      folding/unfolding of T4L.

PMID- 25612732
TI  - The serum opsonin L-ficolin is detected in lungs of human transplant recipients
      following fungal infections and modulates inflammation and killing of Aspergillus
      fumigatus.
AB  - BACKGROUND: Invasive aspergillosis (IA) is a life-threatening systemic fungal
      infection in immunocompromised individuals that is caused by Aspergillus
      fumigatus. The human serum opsonin, L-ficolin, has been observed to recognize A.
      fumigatus and could participate in fungal defense. METHODS: Using lung epithelial
      cells, primary human monocyte-derived macrophages (MDMs), and neutrophils from
      healthy donors, we assessed phagocytosis and killing of L-ficolin-opsonized live
      A. fumigatus conidia by flow cytometry and microscopy. Additionally, cytokines
      were measured by cytometric bead array, and L-ficolin was measured in
      bronchoalveolar lavage (BAL) fluid from lung transplant recipients by enzyme
      linked immunosorbent assay. RESULTS: L-ficolin opsonization increased conidial
      uptake and enhanced killing of A. fumigatus by MDMs and neutrophils. Opsonization
      was also shown to manifest an increase in interleukin 8 release from A549 lung
      epithelial cells but decreased interleukin 1beta, interleukin 6, interleukin 8,
      interleukin 10, and tumor necrosis factor alpha release from MDMs and neutrophils
      24 hours after infection. The concentration of L-ficolin in BAL fluid from
      patients with fungal infection was significantly higher than that for control
      subjects (P = .00087), and receiving operating characteristic curve analysis
      highlighted the diagnostic potential of L-ficolin for lung infection (area under
      the curve, 0.842; P < .0001). CONCLUSIONS: L-ficolin modulates the immune
      response to A. fumigatus. Additionally, for the first time, L-ficolin has been
      demonstrated to be present in human lungs.

PMID- 25612733
TI  - Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection
      Vitamin D Dose Matters.
AB  - Vitamin D level is linked to susceptibility to infections, but its relevance in
      candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3
      supplementation in systemic Candida infection. Implicating the role of vitamin D
      in Candida infections, we showed that candidemic patients had significantly lower
      25-OHD concentrations. Candida-infected mice treated with low-dose 1,25(OH)2D3
      had reduced fungal burden and better survival relative to untreated mice.
      Conversely, higher 1,25(OH)2D3 doses led to poor outcomes. Mechanistically, low
      dose 1,25(OH)2D3 induced proinflammatory immune responses. This was mediated
      through suppression of SOCS3 and induction of vitamin D receptor binding with the
      vitamin D-response elements in the promoter of the gene encoding interferon
      gamma. These beneficial effects were negated with higher vitamin D3 doses. While
      the antiinflammatory effects of vitamin D3 are well described, we found that,
      conversely, lower doses conferred proinflammatory benefits in Candida infection.
      Our study highlights caution against extreme deviations of vitamin D levels
      during infections. 

PMID- 25612736
TI  - Evaluation of indeterminate thyroid cytology by second-opinion diagnosis or
      repeat fine-needle aspiration: which is the best approach?
AB  - OBJECTIVE: This study investigated a published series evaluating the role of
      second-opinion diagnosis (SOD) or repeat fine-needle aspiration cytology (RFNA)
      for indeterminate thyroid aspirates. STUDY DESIGN: Twenty-three studies were
      selected and the following parameters were analyzed: disagreement between SOD or
      RFNA and the original diagnosis (OD), reclassification of OD according to the
      Bethesda system for reporting thyroid cytopathology, the rate of definitive
      diagnosis and the diagnostic performance of SOD and RFNA. RESULTS: 7,154 thyroid
      FNAs were retrieved from 9 studies that investigated the role of SOD, including
      1,048 (14.6%) cases originally reported as indeterminate. The 14 studies that
      analyzed the role of thyroid RFNA comprised 67,581 FNAs and included 7,246
      (10.7%) indeterminate cases. A definitive diagnosis was achieved by SOD in 450
      cases (42.9%) and RFNA in 1,645 cases (57.2%, p=0.0001). Based on cases with
      histological follow-up, SOD demonstrated significantly higher rates of positive
      predictive value and accuracy than RFNA (55.8 vs. 37.7%, p=0.0001; 67.4 vs.
      56.0%, p=0.0034, respectively). CONCLUSIONS: Both SOD and RFNA demonstrated an
      improvement in the diagnosis of initially indeterminate thyroid FNAs. RFNA
      achieved a definitive diagnosis for the majority of indeterminate cases.
      Regarding histological follow-up, SOD was shown to be more accurate than RFNA.

PMID- 25612737
TI  - Separating sets of term and pre-term uterine EMG records.
AB  - The analysis of uterine EMG (electrohysterogram-EHG) records may help solve the
      problem of predicting pre-term labor. We investigated the adaptive autoregressive
      (AAR) method to estimate the EHG signal spectrograms and sample entropy, to
      separate and classify sets of term and pre-term delivery records, using the Term
      Preterm EHG Database. The database contains four sets of records divided
      according to the time of delivery (term or pre-term: ?37 or < 37 weeks of
      gestation, respectively) and according to the time of recording (early or later:
      before or after the 26th week of gestation, respectively). Using the AAR method
      the term and pre-term delivery records recorded early can be separated (p =
      0.002), as well as all term and pre-term delivery records (p < 0.001). Using the
      sample entropy, the results showed that all term and pre-term delivery records
      can be separated (p = 0.022). The spectra of the signals for term delivery
      records have the tendency of moving to lower frequencies as the time of pregnancy
      increases. We investigated a few classifiers to classify records between term and
      pre-term delivery sets. Using median frequency measurements and additional
      clinical information with the synthetic minority over-sampling technique, the
      quadratic discriminant analysis classifier achieved a 97% classification accuracy
      for the records recorded early, and 86% for all records regardless of the time of
      recording; while for the sample entropy measurements, for the same sets of
      records, using the support vector machine classifier, the classification
      accuracies were 80% and 87%, respectively. 

PMID- 25612735
TI  - Transglutaminase 2 promotes PDGF-mediated activation of PDGFR/Akt1 and beta
      catenin signaling in vascular smooth muscle cells and supports neointima
      formation.
AB  - BACKGROUND: Phenotypic switch of vascular smooth muscle cells (VSMCs) accompanies
      neointima formation and associates with vascular diseases. Platelet-derived
      growth factor (PDGF)-induced activation of PDGFR/Akt1 and beta-catenin signaling
      pathways in VSMCs has been implicated in vessel occlusion. Transglutaminase 2
      (TG2) regulates these pathways and its levels are increased in the neointima.
      OBJECTIVE: The aim of this study was to evaluate the role of TG2 in PDGF/beta
      catenin signaling cross-talk and assess its contribution to neointima. METHODS:
      Aortic VSMCs from wild-type and TG2 knockout mice were tested in vitro for levels
      of VSMC markers, proliferation, migration and PDGF-induced activation of
      PDGFR/Akt1 and beta-catenin pathways. Neointima in these mice was studied ex vivo
      in coronary vessels using a heart slice model and in vivo using a carotid artery
      ligation model. RESULTS: Genetic deletion of TG2 attenuated the PDGF-induced
      phenotypic switch of aortic VSMCs, reduced their proliferation and migration
      rates, and inhibited PDGF-induced activation of PDGFR/Akt1 and beta-catenin
      pathways in both ex vivo and in vivo neointima models. Importantly, genetic
      deletion of TG2 also markedly attenuated vessel occlusion. CONCLUSIONS: TG2
      promotes neointima formation by mediating the PDGF-induced activation of the
      PDGFR/Akt1 and beta-catenin pathways in VSMCs. This study identifies TG2 as a
      potential therapeutic target for blocking neointima in blood vessels.

PMID- 25612738
TI  - Pancreatic response to gold nanoparticles includes decrease of oxidative stress
      and inflammation in autistic diabetic model.
AB  - BACKGROUND: Gold nanoparticles (AuNPs) have a wide range of applications in
      various fields. This study provides an understanding of the modulatory effects of
      AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum
      disorder (ASD). Normal littermates fed by control mothers were injected with
      citrate buffer alone and served as normal, untreated controls controlin this
      study. Diabetes mellitus (DM) was induced by administering a single
      intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND)
      diabetic group, which had been fasted overnight. Autistic pups from mothers that
      had received a single intraperitoneal injection of 600 mg/kg sodium valproate on
      day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as
      follow; administering single intraperitoneal injection of streptozotocin (STZ) (
      (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic
      group. The treatment was started on the 5th day after STZ injection with the same
      dose as in group II and it was considered as 1st day of treatment with gold
      nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic
      group(TAD) at a dosage of 2.5 mg/kg. b. wt. RESULTS: At this dose of
      administration AuNPs, the activities of hepatic superoxide dismutase (SOD),
      glutathione peroxidase (GPx), and catalase were greater in group TAD compared
      with the control group (P < 0.05). Oxidised glutathione levels were lower (P >
      0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced
      glutathione was markedly higher than in control rats, especially after
      administration of AuNPs. Moreover, the kidney functions in addition to the fat
      profile scoring supported the protective potential of that dose of AuNPs. The
      beta cells revealed euchromatic nuclei with no evidence of separation of nuclear
      membrane. CONCLUSIONS: Our results showed that AuNPs improved many of the
      oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity
      (ORAC) and lipid profile relative to the other parameters. In addition to the
      apparent reversibility of the pancreatic B cell in group IV which may reflect the
      regenerative capacity of AuNPs.

PMID- 25612734
TI  - Impact of past climatic changes and resource availability on the population
      demography of three food-specialist bees.
AB  - Past climate change is known to have strongly impacted current patterns of
      genetic variation of animals and plants in Europe. However, ecological factors
      also have the potential to influence demographic history and thus patterns of
      genetic variation. In this study, we investigated the impact of past climate, and
      also the potential impact of host plant species abundance, on intraspecific
      genetic variation in three codistributed and related specialized solitary bees of
      the genus Melitta with very similar life history traits and dispersal capacities.
      We sequenced five independent loci in samples collected from the three species.
      Our analyses revealed that the species associated with the most abundant host
      plant species (Melitta leporina) displays unusually high genetic variation, to an
      extent that is seldom reported in phylogeographic studies of animals and plants.
      This suggests a potential role of food resource abundance in determining current
      patterns of genetic variation in specialized herbivorous insects. Patterns of
      genetic variation in the two other species indicated lower overall levels of
      diversity, and that M. nigricans could have experienced a recent range expansion.
      Ecological niche modelling of the three Melitta species and their main host plant
      species suggested a strong reduction in range size during the last glacial
      maximum. Comparing observed sequence data with data simulated using spatially
      explicit models of coalescence suggests that M. leporina recovered a range and
      population size close to their current levels at the end of the last glaciation,
      and confirms recent range expansion as the most likely scenario for M. nigricans.
      Overall, this study illustrates that both demographic history and ecological
      factors may have contributed to shape current phylogeographic patterns. 

PMID- 25612739
TI  - Telomere length variations in aging and age-related diseases.
AB  - Telomeres are gene sequences present at chromosomal ends and are responsible for
      maintaining genome integrity. Telomere length is maximum at birth and decreases
      progressively with advancing age and thus is considered as a biomarker of
      chronological aging. This age associated decrease in the length of telomere is
      linked to various ageing associated diseases like diabetes, hypertension,
      Alzheimer's disease, cancer etc. and their associated complications. Telomere
      length is a result of combined effect of oxidative stress, inflammation and
      repeated cell replication on it, and thus forming an association between telomere
      length and chronological aging and related diseases. Thus, decrease in telomere
      length was found to be important in determining both, the variations in longevity
      and age-related diseases in an individual. Ongoing and progressive research in
      the field of telomere length dynamics has proved that aging and age-related
      diseases apart from having a synergistic effect on telomere length were also
      found to effect telomere length independently also. Here a short description
      about telomere length variations and its association with human aging and age
      related diseases is reviewed. 

PMID- 25612740
TI  - Increased mitochondrial DNA deletions in substantia nigra dopamine neurons of the
      aged rat.
AB  - The dopaminergic neurons of the substantia nigra (SN), which constitute the
      origin of the nigrostriatal system, are vulnerable to age-related degenerative
      processes. For example, in humans there is a relatively small age-related loss of
      neurons but a marked decline of the dopaminergic phenotype associated with
      impaired voluntary motor control. However, the mechanisms responsible for the
      dysfunction and degeneration of SN dopamine neurons remain poorly understood. One
      potential contributor is mitochondrial dysfunction, resulting from an increased
      abundance of mitochondrial DNA (mtDNA) mutations such as deletions. Human studies
      have identified relatively high levels of mtDNA deletions in these cells in both
      aging and Parkinson's disease (>35%), with a higher abundance of deletions (>60%)
      in individual neurons with mitochondrial dysfunction. However, it is unknown
      whether similar mtDNA mutations occur in other species such as the rat. In the
      present study, we quantified mtDNA deletion abundance in laser microdissected SN
      dopaminergic neurons from young and old F344 rats. Our results indicate that
      mtDNA deletions accumulated with age, with approximately 20% more mtDNA deletions
      in SN dopaminergic neurons from old compared to young animals. Thus, while rat SN
      dopaminergic neurons do accumulate mtDNA deletions with aging, this does not
      reflect the deletion burden in humans, and other mechanisms may be operating to
      compensate for age-related mtDNA damage in the rat SN dopaminergic neurons. 

PMID- 25612742
TI  - Status of Bactrocera invadens (Diptera: Tephritidae) in mango-producing areas of
      Arba Minch, southwestern Ethiopia.
AB  - Bactrocera invadens, the Asian fruit fly, was first reported in Kenya in 2003,
      and it spread fast to most tropical countries in Africa. To our knowledge, there
      is no detailed data on the fruit damage and status of fruit flies in Arba Minch
      and elsewhere in Ethiopia. Hence, information on the species composition and pest
      status of the fruit fly species is urgent to plan management strategies in the
      area. Fruit flies were captured using male parapheromone-baited traps. Matured
      mango (Mangifera indica) fruits were collected from randomly selected mango trees
      and incubated individually in cages (15 by 15 by 15 cm) with sandy soil. B.
      invadens was the predominant (96%; 952 of 992) captured species and the only
      fruit fly species emerging from mango fruits incubated in the laboratory. The
      mean number of adult B. invadens emerging per mango fruit was 35.25, indicating
      that the species is the most devastating mango fruit fly in the area. The loss
      due to this species would be serious if no management strategies are implemented.

PMID- 25612743
TI  - Mortality after cardiac surgery in patients with liver cirrhosis classified by
      the Child-Pugh score.
AB  - Liver cirrhosis is a known risk factor for postoperative mortality in patients
      undergoing cardiac surgery. Clinical assessment of liver cirrhosis using the
      widely accepted Child-Pugh (CP) score is thus vital for evaluation of surgical
      options and perioperative care. However, detailed mortality rates as a
      consequence of liver cirrhosis are unclear. This review aimed to stratify the
      risk of short-term (<30 days) and overall (up to 10 years) mortality after
      cardiac surgery in patients with liver cirrhosis, classified by the CP score.
      Thus, PubMed, Embase, CINAHL and the Cochrane Library were systematically
      reviewed by two independent investigators for studies published up to February
      2014, in which mortality in cirrhotic patients, classified by the CP
      classification, undergoing cardiac surgery was evaluated postoperatively. A total
      of 993 articles were identified. After critical appraisal of 21 articles, 19 were
      selected for final analysis. Weighted short-term mortality of cirrhotic patients
      undergoing cardiac surgery was 19.3% [95% confidence interval (CI): 16.4-22.5%].
      Across the different CP groups, short-term mortality appeared to be 9.0% (95% CI:
      6.6-12.2%), 37.7% (95% CI: 30.8-44.3%) and 52.0% (95% CI: 33.5-70.0%) in Groups
      A, B and C, respectively. Weighted overall mortality within 1 year was 42.0% (95%
      CI: 36.0-48.3%) in all cirrhotic patients. Subdivided in groups, overall
      mortality within that 1 year was 27.2% (95% CI: 20.9-34.7%), 66.2% (95% CI: 54.3
      76.3%) and 78.9% (95% CI: 56.1-92.1%) in Groups A, B and C, respectively. In
      conclusion, short-term mortality is considerably increased in patients with liver
      cirrhosis CP class B and C. Overall mortality is significantly high in all
      classes of liver cirrhosis. 

PMID- 25612744
TI  - Increasing neurogenesis with fluoxetine, simvastatin and ascorbic Acid leads to
      functional recovery in ischemic stroke.
AB  - Less than 8.5% of ischemic stroke patients receive clot-busting drugs within the
      narrow time needed to reduce injury. Thus, there is need for an easily-accessible
      delayed post-stroke drug treatment to improve functional recovery. Various
      combinations of fluoxetine, simvastatin, and ascorbic acid were given to healthy
      rats to assess impact on neurogenesis versus controls. Fluoxetine combined with
      simvastatin and ascorbic acid produced a 19-fold increase in neurogenesis versus
      controls in healthy rats; fluoxetine alone produced 10-fold increase. We next
      tried a couple of drug combinations versus control in endothelin-induced stroked
      rats. Combined fluoxetine/ simvastatin/ascorbic acid treatment, given to stroked
      rats 20-26 hours after stroke induction and continued for 31 days, produced
      strong recovery as measured by Montoya staircase test (mean recovery to 85% of
      pre-stroke function) and Forelimb Asymmetry test (mean recovery to 90% of pre
      stroke function). Fluoxetine and ascorbic acid without simvastatin only produced
      ~50% of recovery produced by the 3-drug combination. Our results indicate that
      combined treatment of Fluoxetine, simvastatin and ascorbic acid represents a
      promising delayed stroke treatment that greatly improves functional recovery in
      rats and warrants further study in human patient populations. This work formed
      the basis for a patent submission (US20130065924A1) Composition and method for
      treatment of neurodegeneration. 

PMID- 25612741
TI  - In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a
      in recombinant Escherichia coli: identification of stimulating factors for in
      vivo glycosylation.
AB  - BACKGROUND: Glycoconjugated vaccines composed of polysaccharide antigens
      covalently linked to immunogenic carrier proteins have proved to belong to the
      most effective and safest vaccines for combating bacterial pathogens. The
      functional transfer of the N-glycosylation machinery from Campylobacter jejuni to
      the standard prokaryotic host Escherichia coli established a novel bioconjugation
      methodology termed bacterial glycoengineering. RESULTS: In this study, we report
      on the production of a new recombinant glycoconjugate vaccine against Shigella
      flexneri 2a representing the major serotype for global outbreaks of shigellosis.
      We demonstrate that S. flexneri 2a O-polysaccharides can be transferred to a
      detoxified variant of Pseudomonas aeruginosa carrier protein exotoxin A (EPA) by
      the C. jejuni oligosaccharyltransferase PglB, resulting in glycosylated EPA-2a.
      Moreover, we optimized the in vivo production of this novel vaccine by
      identification and quantitative analysis of critical process parameters for
      glycoprotein synthesis. It was found that sequential induction of
      oligosaccharyltransferase PglB and carrier protein EPA increased the specific
      productivity of EPA-2a by a factor of 1.6. Furthermore, by the addition of 10 g/L
      of the monosaccharide N-acetylglucosamine during induction, glycoconjugate
      vaccine yield was boosted up to 3.1-fold. The optimum concentration of Mg2+ ions
      for N-glycan transfer was determined to be 10 mM. Finally, optimized parameters
      were transferred to high cell density cultures with a 46-fold increase of overall
      yield of glycoconjugate compared to the one in initial shake flask production.
      CONCLUSION: The present study is the first attempt to identify stimulating
      parameters for improved productivity of S. flexneri 2a bioconjugates.
      Optimization of glycosylation efficiency will ultimately foster the transfer of
      lab-scale expression to a cost-effective in vivo production process for a
      glycoconjugate vaccine against S. flexneri 2a in E. coli. This study is an
      important step towards this goal and provides a starting point for further
      optimization studies.

PMID- 25612745
TI  - Biventricular repair for double outlet right ventricle with non-committed
      ventricular septal defect.
AB  - OBJECTIVES: Outcomes of biventricular repair for patients with double outlet
      right ventricle and non-committed ventricular septal defect (DORVncVSD) are not
      well defined. We aim to report our experience with biventricular repair of this
      anomaly in proposing an original surgical management that simplifies the
      anatomical correction. METHODS: From January 2005 to December 2013, 75
      consecutive patients with DORVncVSD who had undergone biventricular repair in our
      institution were retrospectively included. The patients were divided into 2
      groups: 40 patients in Group A had the ventricular septal defect rerouted to the
      aorta, and 35 patients in Group B had the ventricular septal defect rerouted to
      the pulmonary artery. Concomitant tricuspid procedures, conal resection and
      ventricular septal defect enlargement were used to favour intracardiac tunnel
      geometry. RESULTS: Five types of biventricular repair and 16 concomitant
      procedures were performed. Mean age at biventricular repair was 2.2 +/- 2.0
      years. There were 6 (8.0%) early deaths and 4 (6.1%) early intracardiac baffle
      obstructions. During the 4.1 +/- 4.0 years follow-up, 3 (4.3%) late deaths
      occurred with an 87.1% estimated overall survival at 5 years (early deaths
      included). Six late-onset intracardiac tunnel obstructions were noted and three
      of them required reoperation. Comparing the 2 groups, Group A patients have more
      late-onset (6 in Group A vs 0 in Group B, P = 0.026) and overall tunnel
      obstructions (10 in Group A vs 0 in Group B, P = 0.001). Concomitant tricuspid
      procedures significantly reduced intracardiac obstruction (0 in 16 vs 10 in 24, P
      = 0.003) without development of any tricuspid regurgitation and stenosis.
      CONCLUSIONS: Using appropriate intracardiac tunnel establishment strategy and
      techniques, biventricular repair of DORVncVSD is feasible with encouraging
      outcomes. Concomitant tricuspid procedures can reduce intracardiac tunnel
      geometry without increase of mortality and morbidity.

PMID- 25612747
TI  - Free supplies and the appearance of endorsement: distribution of tobacco to
      soldiers and artificial infant formula to new mothers.

PMID- 25612746
TI  - Dilated left atrium as a predictor of late outcome after pulmonary vein isolation
      concomitant with aortic valve replacement and/or coronary artery bypass
      grafting?.
AB  - OBJECTIVES: Left atrial (LA) dimension can predict atrial fibrillation (AF)
      recurrence after catheter-based or surgical ablation. Pulmonary vein isolation
      (PVI) may be a surgical option during aortic valve replacement (AVR) and/or
      coronary artery bypass grafting (CABG), though consensus regarding patient
      selection and late outcome is lacking. METHODS: We studied 160 patients (mean age
      70 +/- 9 years) with paroxysmal AF who underwent radiofrequency-based PVI during
      AVR and/or CABG, and were followed up postoperatively for at least 6 months. Mean
      preoperative LA dimension was 44 +/- 7 mm. Serial echocardiography was performed
      to evaluate left ventricular (LV) and LA dimensions, E/e', estimated systolic
      pulmonary artery (PA) pressure and degree of valvular regurgitation. Follow-up
      was completed with a mean duration of 47 +/- 25 months. RESULTS: At the latest
      follow-up, 133 patients (83%) remained in sinus rhythm. Preoperative LA dimension
      was independently associated with increased risk of AF recurrence at 6 months
      after surgery [adjusted odds ratio 1.3 per 1-mm increase in LA dimension, 95%
      confidence interval (CI) 1.1-1.6, P < 0.001]. Receiver-operating characteristic
      curve analysis demonstrated an optimal cut-off value for preoperative LA
      dimension of 45 mm to predict sinus rhythm restoration (98% for <45 mm vs 55% for
      >=45 mm, P < 0.001). Patients with LA dimension >=45 mm had a significantly lower
      5-year survival rate (62 +/- 7 vs 82 +/- 7%, P = 0.025) and freedom from adverse
      events defined as cerebral infarction/haemorrhage, admission for heart failure,
      catheter ablation and permanent pacemaker implantation (58 +/- 7 vs 91 +/- 4%, P
      < 0.001). Multivariate analysis showed that preoperative LA dimension >=45 mm was
      independently associated with adverse events (adjusted hazards ratio 2.4, 95% CI
      1.2-5.1, P = 0.019). Serial echocardiography demonstrated improvement in LV
      systolic function irrespective of LA dimension, whereas patients with LA
      dimension >=45 mm showed less improvement in LA dimension and systolic PA
      pressure (interaction effect P < 0.001) and persistent higher E/e' (group effect
      P < 0.001), along with aggravated tricuspid regurgitation. CONCLUSIONS: In
      patients with paroxysmal AF related to aortic valve disease and/or coronary
      artery disease, a dilated left atrium (>=45 mm) was associated with inferior AF-
      and event-free survival after PVI, accompanied by persistent abnormalities in
      cardiac and haemodynamic function. These findings may assist patient selection
      for PVI during AVR and/or CABG.

PMID- 25612748
TI  - Behavior of the Newborn during Skin-to-Skin.
AB  - BACKGROUND: Early skin-to-skin contact (SSC) significantly increases the
      breastfeeding rate in healthy term infants. OBJECTIVE: This study aimed to
      confirm previously described behavioral sequences during SSC. METHODS: We
      recorded live and videotaped infant behavioral sequences during SSC in a cohort
      of healthy term infants, whose outcome was then evaluated. RESULTS: We studied 17
      mother-infants dyads. While the majority of infants (59%) had behavioral phases
      that have been previously reported, some of them had alternative sequences. We
      observed the infant's massage of the mother's breast with its hand during SSC,
      which had not been previously reported. We found no correlations between
      behavioral sequence during SSC, breastfeeding, and neonatal outcome. Moreover,
      maternal pain stimuli did not affect the neonatal SSC behavioral sequence.
      CONCLUSION: Our study confirms that immediate and undisturbed postpartum SSC is
      characterized by specific behavioral phases whose sequence may vary without
      affecting the suckling rate at the end of SSC, breastfeeding success, or the
      short-term neonatal outcome.

PMID- 25612749
TI  - Asynchronous milk ejection in human lactating breast: case series.
AB  - BACKGROUND: Milk production is under the influence of autocrine control such that
      the rate of milk synthesis decreases as the breast fills with milk. Effective
      elimination of milk from the alveoli via the milk ejection reflex will therefore
      result in increased milk synthesis. It has been assumed that milk ejection occurs
      in all alveoli simultaneously; however, animal studies have indicated that full
      alveoli eject milk sooner than less full alveoli, suggesting heterogeneous
      emptying of the mammary gland. OBJECTIVE: The aim of this study was to determine
      whether milk ejection occurs asynchronously in the human lactating breast.
      METHODS: Retrospective analysis of videos made of ultrasound monitoring of milk
      ducts during pumping. Six video clips (4 women) of ultrasound monitored milk
      ejections showed obvious differences in the timing of milk flow between different
      main milk ducts. Duct diameter was simultaneously measured every second in 2
      different ducts that drained 2 separate lobes of the breast. RESULTS: For 5 of 6
      ultrasound duct monitoring sessions, both duct dilation and visualization of milk
      flow in the 2 separate main milk ducts differed by 2 to 8 seconds. For the
      remaining woman, milk was observed to eject from 1 part of the lobe, and when not
      removed, it flowed in a retrograde fashion into a different part of the lobe.
      CONCLUSION: Asynchrony of milk ejection occurs in the human lactating breast,
      suggesting that the timing of myoepithelial cell response differs, resulting in
      heterogeneous emptying of the gland.

PMID- 25612750
TI  - 4D flow preliminary investigation of a direct carotid cavernous fistula due to a
      ruptured intracavernous aneurysm.
AB  - Inadequate information is available about the cerebral blood flow and surgical
      strategies of a direct aneurysmal carotid cavernous fistula (daCCF). We report a
      quantitative analysis of flow velocity and volume using preoperative time
      resolved phase-contrast MRI (four-dimensional (4D) flow MRI) in a daCCF. This is
      the first report of 4D flow findings with a daCCF. A 55-year-old woman developed
      a sudden headache and bruit of the right orbit, and MRI suggested the presence of
      a daCCF. Quantitative analysis using preoperative 4D flow MRI revealed the flow
      volume of the right internal carotid artery. The daCCF was successfully treated
      by high-flow bypass using a radial artery graft and internal carotid artery
      trapping. Postoperative angiography showed a complete obliteration of the daCCF.
      Studies to collect data from additional cases are required so that 4D flow
      findings can be further used in the management of daCCFs. 

PMID- 25612751
TI  - An unusual swelling in the male perineum.
AB  - Median raphe cysts are a rare, congenital entity. We present a case and review
      the literature in respect to a 35-year-old man with a non-visible, painless
      midline swelling in the anterior perineum initially thought to be a liposarcoma.
      Subsequent histopathological examination confirmed a median raphe cyst. 

PMID- 25612752
TI  - Neurosarcoidosis-associated central diabetes insipidus masked by adrenal
      insufficiency.
AB  - Central diabetes insipidus (CDI) is an infrequent complication of
      neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency
      (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a
      history of NS presented 2 weeks after abrupt cessation of prednisone with nausea,
      vomiting, decreased oral intake and confusion. She was diagnosed with secondary
      AI and intravenous hydrocortisone was promptly begun. Over the next few days,
      however, the patient developed severe thirst and polyuria exceeding 6 L of urine
      per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed
      to have CDI due to NS, and intranasal desmopressin was administered. This
      eventually normalised her urine output and serum sodium. The patient was
      discharged improved on intranasal desmopressin and oral prednisone. AI may mask
      the manifestation of CDI because low serum cortisol impairs renal-free water
      clearance. Steroid replacement reverses this process and unmasks an underlying
      CDI. 

PMID- 25612753
TI  - A case of lissencephaly in a 5-month-old infant.

PMID- 25612754
TI  - Pregnancy and ABCB4 gene mutation: risk of recurrent cholelithiasis.
AB  - Cholelithiasis is a common problem in the Western world. Recurrent gallstones
      after cholecystectomy, however, are rare. We describe a case of a young woman
      with recurrent gallstones after a laparoscopic cholecystectomy leading to
      cholangitis during pregnancy. Additional testing revealed an ATP-binding cassette
      B4 (ABCB4) gene mutation. ABCB4 gene mutations leading to a multidrug resistance
      (MDR)3-P-glycoprotein deficiency are related to, among other diseases, recurrent
      cholelithiasis. Medical treatment consists of administering oral ursodeoxycholic
      acid. If untreated, MDR3 deficiency can lead to progressive liver failure
      requiring liver transplantation. 

PMID- 25612755
TI  - A case of nausea and vomiting to remember.
AB  - Nausea and vomiting are the most common overlooked debilitating symptoms that
      significantly impact the quality of life and acute care we provide as physicians.
      The duo has an extensive aetiology ranging from common known causes to uncommon
      idiopathic reasons. Our case illustrates the fact that identifying the aetiology
      of nausea and vomiting can be lifesaving, given the characteristics of the
      patient. This case is about a 31-year-old Caucasian woman, with history
      significant for insulin-dependent diabetes mellitus on insulin pump since the age
      2, Hypothyroidism, diabetic peripheral neuropathy with no significant known
      family history, who was admitted with intractable nausea and vomiting. She was
      discharged twice from hospital after temporary symptom control with presumed
      diagnosis of diabetic gastroparesis. Her third hospital visit enabled us to
      identify the cause of her symptoms being Addison's crisis rather than
      gastroparesis. 

PMID- 25612756
TI  - Abdominal cocoon: idiopathic sclerosing encapsulating peritonitis.
AB  - Abdominal cocoon, or idiopathic sclerosing encapsulating peritonitis, is a rare
      condition characterised by the presence of a dense fibrocollagenous membrane
      partially or totally encapsulating the small bowel leading to recurrent
      intestinal obstructions. We present the case of a patient who has presented for
      the fourth time with a small bowel obstruction. Previous laparoscopy revealed a
      plaque-like reactive process encapsulating much of the small bowel and the liver.
      After initial adhesiolysis, the patient's obstructions continued to reoccur.
      Further laparotomy was performed in order to excise the entirety of the cocoon
      membrane and free up loops of small bowel encapsulated by the process, hopefully
      preventing future obstructions. 

PMID- 25612757
TI  - False detection of atrial fibrillation in children by a blood pressure monitor
      with atrial fibrillation detection function.
AB  - A sphygmomanometer that can detect atrial fibrillation may help to identify
      asymptomatic patients who might benefit from anticoagulation. Its performance in
      young people has not been reported. In a school project measuring blood pressure
      in 60 normal healthy male teenagers (age range 13-18 years; mean+/-SD 15.0+/-1.5
      years), a Microlife BPA200 blood pressure monitor indicated atrial fibrillation
      in 11 participants (18%). These participants did not have any personal or family
      history of heart disease. They had sinus arrhythmia and had significantly lower
      systolic and diastolic blood pressure, body mass index and waist circumference
      (all p values <0.05). In young people, atrial fibrillation is very uncommon and
      false positives are likely. To avoid unnecessary alarm and referrals, this
      function is best turned off in young patients. 

PMID- 25612758
TI  - Successful surgical optic nerve decompression in a patient with hypertrophic
      pachymeningitis due to granulomatous polyangiitis.
AB  - A 57-year-old woman presented with subacute vision loss of first the left, and
      later the right eye. She was diagnosed with granulomatous polyangiitis with
      hypertrophic pachymeningitis and optic nerve compression. Her visual acuity could
      not be permanently restored with immune suppressants alone, so a surgical
      decompression of the right optic nerve, via a modified cranio-orbitozygomatic
      pretemporal approach, was performed. Her right eye regained 20/20 vision and has
      remained stable during 8 months of follow-up. 

PMID- 25612759
TI  - The migrant worker: visible, yet invisible.
AB  - Immigrant workers are a vulnerable and underserved population. The average life
      expectancy of the migrant worker is 49 years, compared to 77.2 years for most
      Americans. Immigrant workers have a higher disease burden than other populations
      and work in occupations with high hazard levels. In addition, they have low
      socioeconomic levels and face many barriers to accessing healthcare services.
      Undocumented immigrant workers are excluded in the Affordable Care Act. Health
      professionals must be attuned to the health issues of new immigrants so that they
      can provide better services. In order to raise the health standards of America,
      health professionals must provide healthcare for all, including immigrant
      workers. 

PMID- 25612760
TI  - Pros and cons of legislation on allogeneic hematopoietic stem cell
      transplantation.

PMID- 25612762
TI  - Non-communicable diseases and adherence to Mediterranean diet.
AB  - Non-communicable diseases (NCDs) also known as chronic diseases last for a long
      time and progress generally slow. Major non-communicable diseases are
      cardiovascular diseases, cancers, chronic respiratory diseases and diabetes.
      Unhealthy lifestyles and food behaviours play an important role for determining
      such diseases. The change in unhealthy behaviours or the maintenance of healthy
      lifestyles has enormous value in the reduction of diseases and longer life
      expectancy not only on an individual level but for the community as a whole.
      Recent meta-analyses reported Mediterranean diet to be an optimal diet when
      adopted as a whole, in order to preserve and maintain a good health status. A
      greater adherence score to the Mediterranean diet (2-point increase) was related
      to induce an 8% reduction in overall mortality, a 10% reduced risk of CVD and a
      4% reduction in neoplastic diseases. However, there is no direct method in
      quantifying and evaluating adherence, therefore a large number of indirect
      indices in several studies have been proposed, with a last unifying score.
      Recently more and more e-health techniques such as web communication or desktop
      publishing (DVDs and so on) are being used, obtaining good results in the
      Mediterranean diet adherence. For successfully changing the unhealthy lifestyles
      and food behaviours of the population, interventions at all levels are needed
      with the cooperation of Institutions, mass media, agricultural and food industry
      and healthcare professionals guided by expert scientific societies. 

PMID- 25612761
TI  - A Phase II study of S-1 and irinotecan combination therapy in previously treated
      patients with advanced non-small cell lung cancer.
AB  - OBJECTIVE: This Phase II study was conducted to evaluate the efficacy and safety
      of S-1 and irinotecan combination therapy as a second-line treatment in patients
      with advanced non-small cell lung cancer. METHODS: Irinotecan was administered at
      60 mg/m(2) on Days 1 and 8. Oral S-1 was administered on Days 1-14 every 3 weeks
      at 80 mg/day for patients with a body surface area of <1.25 m(2), 100 mg/day for
      patients with a body surface area of 1.25-1.5 m(2) and 120 mg/day for patients
      with a body surface area of >1.5 m(2). The primary endpoint was response rate,
      while the secondary endpoints were progression-free survival, overall survival
      and safety. RESULTS: Thirty-one patients were enrolled in this study. The
      response and disease control rates were 6.5 and 58.1%, respectively. Progression
      free survival and median survival time were 2.8 and 12.6 months, respectively.
      Grade 3-4 adverse events were reported for 29.0% of the patients. Hematological
      toxicities of Grade 3 or 4 included leukopenia (9.7%), neutropenia (9.7%),
      febrile neutropenia (3.2%), thrombopenia (3.2%) and anemia (6.5%). Non
      hematological toxicities of Grade 3 or 4 included pneumonitis (6.5%), diarrhea,
      colitis, dyspnea, rash, oral mucositis, anorexia and pulmonary
      thromboembolism/deep vein thrombosis (3.2% each). CONCLUSIONS: S-1 and irinotecan
      combination therapy at the present dose and schedule exhibited only modest
      efficacy with mild toxicities in previously treated patients with non-small cell
      lung cancer. No further clinical investigation with current dose and schedules is
      warranted for patients with non-small cell lung cancer who failed first-line
      platinum-based doublet chemotherapy.

PMID- 25612763
TI  - Ultrasound credentialing in North American emergency department systems with
      ultrasound fellowships: a cross-sectional survey.
AB  - OBJECTIVE: To describe the credentialing systems of North American emergency
      department systems (EDS) with emergency ultrasound (EUS) fellowship programmes.
      METHODS: This is a prospective, cross-sectional, survey-based study of North
      American EUS fellowships using a 62-item, pilot-tested, web-based survey
      instrument assessing credentialing and training systems. The American College of
      Emergency Physicians (ACEP) distributed the surveys using SNAP survey (Snap
      Surveys Ltd, Portsmouth, New Hampshire, USA). RESULTS: Over 6 months, 75 eligible
      programmes were surveyed, 55 responded (73% response rate); 1 declined to
      participate leaving 54 participating programmes. Less than 20% of EDS credential
      nurses, physician assistants, nurse practitioners and students in EUS. Respondent
      EDS reported having an average of 4.2 +/- 3.3 ultrasound faculty members (faculty
      identifying their career focus as EUS). The median number of annual point-of-care
      ultrasounds reported was 5000 (IQR 3000-8000). 30 EDS (56%) credential each
      examination individually and 48 EDS (89%) use ACEP credentialing criteria. 61% of
      fellowship leadership believe their credentialing system is either satisfactory
      or very satisfactory (Cronbach's coefficient alpha=0.84). CONCLUSIONS: The data
      show heterogeneity among North American EDS with EUS fellowship programmes with
      regard to credentialing systems despite published guidelines from the ACEP and
      Canadian Emergency Ultrasound Society.

PMID- 25612764
TI  - Use of inertial sensors to predict pivot-shift grade and diagnose an ACL injury
      during preoperative testing.
AB  - BACKGROUND: The pivot-shift (PS) examination is used to demonstrate knee
      instability and detect anterior cruciate ligament (ACL) injury. Prior studies
      using inertial sensors identified the ACL-deficient knee with reasonable
      accuracy, but none addressed the more difficult problem of using these sensors to
      determine whether a subject has an ACL deficiency and to correctly assign a PS
      grade to a patient's knee. HYPOTHESIS: Inertial sensor data recorded during a PS
      examination can accurately predict ACL deficiency and the PS score assigned by
      the examining physician. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 2. METHODS: A total of 32 patients with unilateral ACL deficiency and
      29 with intact ACLs in both knees had inertial sensor modules strapped to the
      tibia and femur of each limb for preoperative PS testing under anesthesia.
      Support vector machine (SVM) methods assessed PS grades on the basis of these
      data, with the examiner's clinical grading shift used as ground truth. A fusion
      of regression and SVM classification techniques diagnosed ACL deficiency.
      RESULTS: The clinically determined PS grades of all 122 knees were as follows: 0
      (n = 69), +1 (n = 23), +2 (n = 27), and +3 (n = 3). The SVM classification
      analysis was 77% accurate in correctly classifying these grades, with 98% of
      computed PS grades falling within +/-1 grade of the clinically determined value.
      The system fusion algorithm diagnosed ACL deficiency in an individual with an
      overall accuracy of 97%. This method yielded 6% false negatives and 0% false
      positives. CONCLUSION: This study used inertial sensor technology with SVM
      algorithms to accurately determine clinically assigned PS grades in ACL-intact
      and ACL-deficient knees. By extending the assessment to a separate group of
      patients without ACL injury, the inertial sensor data demonstrated highly
      accurate diagnosis of ACL deficiency.

PMID- 25612765
TI  - Whole-exome characterization of pancreatic neuroendocrine tumor cell lines BON-1
      and QGP-1.
AB  - The human BON-1 and QGP-1 cell lines are two frequently used models in pancreatic
      neuroendocrine tumor (PNET) research. Data on the whole-exome genetic
      constitution of these cell lines is largely lacking. This study presents, to our
      knowledge, the first whole-exome profile of the BON-1 and QGP-1 cell lines. Cell
      line identity was confirmed by short tandem repeat profiling. Using GTG-banding
      and a CytoSNP-12v2 Beadchip array, cell line ploidy and chromosomal alterations
      were determined in BON-1 and QGP-1. The exomes of both cell lines were sequenced
      on Ilumina's HiSeq next-generation sequencing (NGS) platform. Single-nucleotide
      variants (SNVs) and insertions and deletions (indels) were detected using the
      Genome Analysis ToolKit. SNVs were validated by Sanger sequencing. Ploidy of BON
      1 and QGP-1 was 3 and 4 respectively, with long stretches of loss of
      heterozygosity across multiple chromosomes, which is associated with aggressive
      tumor behavior. In BON-1, 57 frameshift indels and 1725 possible protein-altering
      SNVs were identified in the NGS data. In the QGP-1 cell line, 56 frameshift
      indels and 1095 SNVs were identified. ATRX, a PNET-associated gene, was mutated
      in both cell lines, while mutation of TSC2 was detected in BON-1. A mutation in
      NRAS was detected in BON-1, while KRAS was mutated in QGP-1, implicating
      aberrations in the RAS pathway in both cell lines. Homozygous mutations in TP53
      with possible loss of function were identified in both cell lines. Various MUC
      genes, implicated in cell signaling, lubrication and chemical barriers, which are
      frequently expressed in PNET tissue samples, showed homozygous protein-altering
      SNVs in the BON-1 and QGP-1 cell lines.

PMID- 25612766
TI  - Quantitative prediction of class I MHC/epitope binding affinity using QSAR
      modeling derived from amino acid structural information.
AB  - The activation of T cell immune responses, which relies on peptide antigens
      transported by TAP and bound to major histocompatibility complex (MHC) molecules,
      is recognized by T cell receptors (TCR). The quantitative prediction of MHC
      epitope binding affinity can facilitate epitope screening and reduce cost and
      experimental efforts greatly. In this study, a comprehensive quantitative
      prediction method of binding affinity was established using quantitative
      structureactivity relationship (QSAR) modeling derived from amino acid
      physicochemical information. Firstly, the epitope was characterized by a set of
      amino acid physicochemical parameters. Secondly, the structural variables were
      optimized by the stepwise regression (STR). Finally, the robust quantitative
      models with were built by multiple linear regressions (MLR) for 31 MHC Class I
      subtypes. The normalized regression coefficients (NRCs) of QSAR model could
      demonstrate the mechanism of interaction of MHC, epitope, and TCR very well. The
      contribution of amino acid at each position of epitope, which was calculated by
      NRC, could determine which one was favorable for binding affinity or not.
      Therefore, the quantitative models established by STR-MLR could be used to guide
      virtual combinational design and high throughout screening of CTL epitope.
      Besides, they have many advantages, such as definite physiochemical indication,
      easier calculation and explanation, and good performances. 

PMID- 25612767
TI  - Modelling of noble anaesthetic gases and high hydrostatic pressure effects in
      lipid bilayers.
AB  - Our objective was to study molecular processes that might be responsible for
      inert gas narcosis and high-pressure nervous syndrome. The classical molecular
      dynamics trajectories (200 ns) of dioleoylphosphatidylcholine (DOPC) bilayers
      simulated by the Berger force field were evaluated for water and the atomic
      distribution of noble gases around DOPC molecules in the pressure range of 1-1000
      bar and at a temperature of 310 K. Xenon and argon have been tested as model
      gases for general anaesthetics, and neon has been investigated for distortions
      that are potentially responsible for neurological tremors in hyperbaric
      conditions. The analysis of stacked radial pair distribution functions of DOPC
      headgroup atoms revealed the explicit solvation potential of the gas molecules,
      which correlates with their dimensions. The orientational dynamics of water
      molecules at the biomolecular interface should be considered as an influential
      factor, while excessive solvation effects appearing in the lumen of membrane
      embedded ion channels could be a possible cause of inert gas narcosis. All the
      noble gases tested exhibit similar order parameter patterns for both DOPC acyl
      chains, which are opposite of the patterns found for the order parameter curve at
      high hydrostatic pressures in intact bilayers. This finding supports the
      'critical volume' hypothesis of anaesthesia pressure reversal. The irregular
      lipid headgroup-water boundary observed in DOPC bilayers saturated with neon in
      the pressure range of 1-100 bar could be associated with the possible
      manifestation of neurological tremors at the atomic scale. The non-immobiliser
      neon also demonstrated the highest momentum impact on the normal component of the
      DOPC diffusion coefficient representing the monolayer undulation rate, which
      indicates that enhanced diffusivity rather than atomic size is the key factor. 

PMID- 25612768
TI  - Common statin side effects explain poor compliance.

PMID- 25612769
TI  - The Relationship Between Childhood Gender Nonconformity and Experiencing Diverse
      Types of Homophobic Violence.
AB  - Experiences of homophobic violence seem to differ for various sexual-minority
      subgroups. Previous research has outlined that experiences differ for men and
      women, and for gender conforming and nonconforming lesbian, gay, and bisexual men
      and women (LGBs). In this article, these relationships are studied by making a
      distinction between four types of homophobic violence: verbal, physical,
      material, and sexual. In 2013, an online survey was designed to ask Flemish LGBs
      about their experiences of homophobic violence. The final sample consists of
      1,402 Flemish sexual-minority individuals. The results show that gay and bisexual
      men experienced significantly more physical, material, and sexual violence during
      their lifetime than lesbian and bisexual women did. Moreover, LGBs who reported
      more childhood gender nonconformity also reported more homophobic violence, and
      this positive relationship is confirmed for the four forms of violence. For
      verbal and physical violence, however, the relationship between childhood gender
      nonconformity and violence varies according to the gender of the respondents.
      This relationship is much stronger for gay and bisexual men than for lesbian and
      bisexual women. 

PMID- 25612771
TI  - Simultaneous determination of six alkaloid components in rat plasma and its
      application to pharmacokinetic study of Danmu preparations by an ultra fast
      liquid chromatography-electrospray ionization-tandem mass spectrometry.
AB  - Danmu injection and Danmu tablet are two widely used traditional Chinese medicine
      made of Nauclea officinalis (commonly known as Danmu), in which the alkaloids are
      the major active substances. In this paper, an ultra fast liquid chromatography
      tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous
      determination and the pharmacokinetic characteristics study of six main active
      alkaloids (naucleamide A-10-O-beta-d-glucopyranosid, naucleamide G, pumiloside, 3
      epi-pumiloside, strictosamide and vincosamide) of the two above-mentioned Danmu
      preparations in rat plasma. In the course of the experiment, following sample
      preparation by protein precipitation with methanol-ethyl acetate (2:1, v/v), the
      nitrogen-dried extraction was reconstituted in methanol and assayed on a C18
      column using a gradient elution program with mobile phase consisting of
      acetonitrile and water containing 0.1% formic acid. The MS detection was
      performed in positive ionization mode with selected ion transitions. The
      established method was fully validated and proved to be sensitive and specific
      with lower limits of quantification (LLOQs) all less than 0.32ng/mL in rat plasma
      and matrix effects ranged from 88.87 to 108.27%. Good linearities of six
      alkaloids were obtained in respective concentration ranges (r(2)>0.995). The
      average extract recoveries for each compound at three quality control
      concentration levels were no less than 79.70%, and the precision and accuracy
      were within the acceptable limits. The validated method was successfully applied
      to the pharmacokinetic study of six alkaloid components of Danmu injection and
      tablet in rat plasma. The obtained results may be helpful to reveal the action
      mechanism and guide the clinical application of Danmu preparations. 

PMID- 25612770
TI  - Development and validation of determinative and confirmatory LC-MS/MS
      methodologies for total florfenicol and tulathromycin residues in bovine, equine
      and porcine kidney, liver and muscle tissues.
AB  - Separate methods for the quantitation and confirmation of regulatory relevant
      residue concentrations of total florfenicol and tulathromycin residues in
      multiple tissue matrices were developed and validated. Total florfenicol
      residues, determined and expressed as florfenicol amine (FFA) equivalents, were
      quantified and confirmed over a concentration range of 100-4000ng/g, with an LOD
      of 33ng/g, while total tulathromyicn residues, determined as CP-60,300 and
      expressed as tulathromycin equivalents, were quantified and confirmed over a
      concentration range of 500-10,000ng/g, with an LOD of 300ng/g. A 2 or 1h acid
      digestion for the FFA and tulathromycin methods, respectively, followed by
      extraction, cleanup, and concentration using mixed-mode strong cation-exchange
      SPE cartridges was used. Quantitation and confirmation were accomplished using
      commercially available tri-deuterated FFA (FFA-D3) as internal standard and
      multiple reaction monitoring (MRM) of three transitions per target analyte. Mean
      recoveries and matrix effects were 60% and 25%; and 100% and 110%, respectively
      for the target analytes florfenicol amine and CP-60,300. Intra-lab method
      reproducibilities ranged from 7 to 11% RSD, which are within the AOAC recommended
      HORRATr guidelines for method reproducibilities estimated from single laboratory
      validation studies. Blind spikes showed that method bias was generally less than
      15% for both methods within the calibration range. Both methods have been shown
      to meet requirements for use in national chemical residue monitoring programs. 

PMID- 25612772
TI  - Liquid chromatography-tandem mass spectrometry assay for the simultaneous
      quantification of simvastatin, lovastatin, atorvastatin, and their major
      metabolites in human plasma.
AB  - Millions of individuals are treated with a variety of statins that are
      metabolized to a variety of active metabolites. A single assay capable of
      simultaneously quantifying commonly used statins and their major metabolites has
      not been previously reported. Herein we describe the development and validation
      of a novel and robust liquid chromatography-tandem mass spectrometry assay for
      simultaneously quantifying simvastatin, lovastatin, atorvastatin, and their
      metabolites, simvastatin acid, lovastatin acid, para-hydroxy atorvastatin, and
      ortho-hydroxy atorvastatin in human plasma. Plasma samples were processed with a
      simple protein precipitation technique using acetonitrile, followed by
      chromatographic separation using an Agilent Zorbax Extend C18 column. A 12.0min
      linear gradient elution was used at a flow rate of 400MUL/min with a mobile phase
      of water and methanol, both modified with 2mM ammonium formate and 0.2% formic
      acid. The analytes and internal standard, hesperetin, were detected using the
      selected reaction monitoring mode on a TSQ Quantum Discovery mass spectrometer
      with positive electrospray ionization. The assay exhibited a linear range of 1
      1000nM for simvastatin acid and lovastatin acid, and a linear range of 0.1-100nM
      for the other analytes in human plasma. The accuracy and the within- and between
      day precisions of the assay were within acceptable ranges, and the method was
      successfully utilized to quantify the statins and their metabolites in human
      plasma samples collected from an ongoing pharmacokinetic study. 

PMID- 25612773
TI  - Effects of a triplex mixture of Peganum harmala, Rhus coriaria, and Urtica dioica
      aqueous extracts on metabolic and histological parameters in diabetic rats.
AB  - CONTEXT: Several therapeutic effects such as antioxidant and blood glucose
      lowering activities have been reported for Peganum harmala L (Zygophyllaceae)
      (PH) seeds, Rhus coriaria L (Anacardiaceae) (RC) fruits, and Urtica dioica L
      (Urticaceae) (UD) leaves. OBJECTIVE: This study investigates the effects of a
      triplex mixture (1:1:1) of these medicinal plants on metabolic and histological
      parameters in diabetic rats. MATERIALS AND METHODS: Aqueous extracts of PH, RC
      and UD were administered as either monotherapy or in combination at a final dose
      of 200 mg/kg to alloxan-induced diabetic rats by daily gavage. Biochemical
      parameters including blood glucose, liver function-related enzymes, lipid
      profile, and creatinine were estimated by spectrophotometric methods. Tissues
      from the liver and kidney stained with hematoxylin/eosin were histologically
      examined. The results obtained from the exposure groups were compared to either
      healthy or diabetic control groups. RESULTS: Compared with the diabetic control
      rats, all aqueous extracts (ED50 = 11.5 +/- 2.57 mg/ml) led to significant
      decreases in the levels of ALP (1.39-2.23-fold, p < 0.05), low-density
      lipoprotein cholesterol (LDL-C) (1.79-3.26-fold, p < 0.05), and blood glucose
      (1.27-4.16-fold, p < 0.05). The serum concentrations of TG was decreased only by
      treatment with UD and triplex mixture (1.25- and 1.20-fold, respectively, p <
      0.05). Among the studied parameters, alanine aminotransferase (ALT), LDL-C, TG,
      and creatinine recovered to healthy control levels after 4 weeks of treatment
      with the extract mixture. CONCLUSION: This study showed that PH, RC, and UD
      extracts, especially their combination, had significant antidiabetic,
      hypolipidemic, and liver and renal damage recovering effects.

PMID- 25612775
TI  - In vivo hair growth-stimulating effect of medicinal plant extract on BALB/c nude
      mice.
AB  - CONTEXT: Chrysanthemum zawadskii var. latilobum (Asteraceae) (CZ) and Polygonum
      multiflorum Thunb. (Polygonaceae) (PM) have been used traditionally to treat
      different systemic diseases and acclaimed for various biological activities
      including hair growth. OBJECTIVE: This study investigates the hair restoration
      efficacy of selected medicinal plant extracts on nude mice. MATERIALS AND
      METHODS: Nude mice genetically predisposed to pattern balding were used in this
      study. Topical methanol extracts of CZ and PM (10 mg/mouse/d) with standardized
      vehicle formulation, only vehicle (propylene glycol:ethanol:dimethyl sulfoxide,
      67:30:3% v/v) and Minoxidil (2%) were applied daily for 40 consecutive days.
      RESULTS: In our study, the maximum hair score (2.5 +/- 0.29) was obtained in the
      CZ-treated group. Histological observation revealed a significant increase (p <
      0.001) in the number of hair follicles (HF) in CZ-treated mice (58.66 +/- 3.72)
      and Minoxidil-treated mice (40 +/- 2.71). Subsequently, immunohistochemical
      analysis also confirmed the follicular keratinocyte proliferation by detection of
      BrdU-labeling, S-phase cells in Minoxidil and CZ-treated mouse follicular bulb
      and outer root sheaths. CONCLUSION: Our study revealed the underlying mechanism
      of stimulating hair growth in athymic nude mice by repair the nu/nu follicular
      keratin differentiation defect. Thus, the topical application of CZ may represent
      a novel strategy for the management and therapy of certain forms of alopecia.

PMID- 25612774
TI  - Potent anti-proliferative effects against oral and cervical cancers of Thai
      medicinal plants selected from the Thai/Lanna medicinal plant recipe database
      "MANOSROI III".
AB  - CONTEXT: Thai/Lanna medicinal plant recipes have been used for the treatment of
      several diseases including oral and cervical cancers. OBJECTIVE: To investigate
      anti-proliferative activity on human cervical (HeLa) and oral (KB) cancer cell
      lines of medicinal plants selected from Thai/Lanna medicinal plant recipe
      database "MANOSROI III". MATERIALS AND METHODS: Twenty-three methanolic plant
      crude extracts were tested for phytochemicals and anti-proliferative activity on
      HeLa and KB cell lines for 24 h by the sulforhodamine B (SRB) assay at the doses
      of 1 * 10(1)-1 * 10(-6 )mg/ml. The nine extracts with the concentrations giving
      50% growth inhibition (GI50) lower than 100 ug/ml were further semi-purified by
      liquid/liquid partition in order to evaluate and enhance the anti-proliferative
      potency. RESULTS: All extracts contained steroids/triterpenoids, but not
      xanthones. The methanolic extracts of Gloriosa superba L. (Colchinaceae) root and
      Albizia chinensis (Osbeck) Merr. (Leguminosae-Mimosoideae) wood gave the highest
      anti-proliferative activity on HeLa and KB cell lines with the GI50 values of
      0.91 (6.0- and 0.31-fold of cisplatin and doxorubicin) and 0.16 ug/ml (28.78- and
      82.29-fold of cisplatin and doxorubicin), respectively. Hexane and methanol-water
      fractions of G. superba exhibited the highest anti-proliferative activity on HeLa
      and KB cell lines with the GI50 values of 0.15 (37- and 1.9-fold of cisplatin and
      doxorubicin) and 0.058 ug/ml (77.45- and 221.46-fold of cisplatin and
      doxorubicin), respectively. DISCUSSION AND CONCLUSION: This study has
      demonstrated the potential of plants selected from MANOSROI III database
      especially G. superba and A. chinensis for further development as anti-oral and
      cervical cancer agents.

PMID- 25612777
TI  - Biological activities of salvianolic acid B from Salvia miltiorrhiza on type 2
      diabetes induced by high-fat diet and streptozotocin.
AB  - CONTEXT: Salvia miltiorrhiza Bge. (Labiatae) has been widely used for treating
      diabetes for centuries. Salvianolic acid B (SalB) is the main bioactive component
      in Salvia miltiorrhiza; however, its antidiabetic activity and possible mechanism
      are not yet clear. OBJECTIVE: To investigate the effects of SalB on
      glycometabolism, lipid metabolism, insulin resistance, oxidative stress, and
      glycogen synthesis in type 2 diabetic rat model. MATERIALS AND METHODS: High-fat
      diet (HFD) and streptozotocin-induced diabetic rats were randomly divided into
      model group, SalB subgroups (50, 100, and 200 mg/kg), and rosiglitazone group.
      RESULTS: Compared with the model group, SalB (100 and 200 mg/kg) significantly
      decreased blood glucose (by 23.8 and 21.7%; p < 0.05 and p < 0.01) and insulin
      (by 31.3 and 26.6%; p < 0.05), and increased insulin sensitivity index (by 10.9
      and 9.3%; p < 0.05). They also significantly decreased total cholesterol (by 24.9
      and 27.9%; p < 0.01), low-density lipoprotein cholesterol (by 56.2 and 64.6%; p <
      0.01), non-esterified fatty acids (by 32.1 and 37.9%; p < 0.01), hepatic glycogen
      (by 41.3 and 60.5%; p < 0.01), and muscle glycogen (by 33.2 and 38.6%; p < 0.05),
      and increased high-density lipoprotein cholesterol (by 50.0 and 61.4%; p < 0.05
      and p < 0.01), which were originally altered by HFD and streptozotocin. In
      addition, SalB (200 mg/kg) markedly decreased triglyceride and malondialdehyde
      (by 31.5 and 29.0%; p < 0.05 and p < 0.01), and increased superoxide dismutase
      (by 56.6%; p < 0.01), which were originally altered by HFD and streptozotocin.
      DISCUSSION AND CONCLUSION: The results indicate that SalB can inhibit symptoms of
      diabetes mellitus in rats and these effects may partially be correlated with its
      insulin sensitivity, glycogen synthesis and antioxidant activities.

PMID- 25612776
TI  - Differential effects of the essential oils of Lavandula luisieri and Eryngium
      duriaei subsp. juresianum in cell models of two chronic inflammatory diseases.
AB  - CONTEXT: Effective drugs to treat osteoarthritis (OA) and inflammatory bowel
      disease (IBD) are needed. OBJECTIVE: To identify essential oils (EOs) with anti
      inflammatory activity in cell models of OA and IBD. MATERIALS AND METHODS: EOs
      from Eryngium duriaei subsp. juresianum (M. Lainz) M. Lainz (Apiaceae),
      Laserpitium eliasii subsp. thalictrifolium Sennen & Pau (Apiaceae), Lavandula
      luisieri (Rozeira) Rivas-Martinez (Lamiaceae), Othantus maritimus (L.) Hoff. &
      Link (Asteraceae), and Thapsia villosa L. (Apiaceae) were analyzed by GC and
      GC/MS. The anti-inflammatory activity of EOs (5-200 MUg/mL) was evaluated by
      measuring inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB (NF
      kappaB) activation (total and phosphorylated IkappaB-alpha), in primary human
      chondrocytes and the intestinal cell line, C2BBe1, stimulated with interleukin
      1beta (IL-1beta) or interferon-gamma (IFN-gamma), IL-1beta and tumor necrosis
      factor-alpha (TNF-alpha), respectively. RESULTS: The EO of L. luisieri
      significantly reduced iNOS (by 54.9 and 81.0%, respectively) and phosphorylated
      IkappaB-alpha (by 87.4% and 62.3%, respectively) in both cell models. The EO of
      E. duriaei subsp. juresianum caused similar effects in human chondrocytes, but
      was inactive in intestinal cells, even at higher concentrations. The EOs of L.
      eliasii subsp. thalictrifolium and O. maritimus decreased iNOS expression by 45.2
      +/- 8.7% and 45.2 +/- 6.2%, respectively, in C2BBe1 cells and were inactive in
      chondrocytes. The EO of T. villosa was inactive in both cell types. DISCUSSION
      AND CONCLUSION: This is the first study showing anti-inflammatory effects of the
      EOs of L. luisieri and E. duriaei subsp. juresianum. These effects are specific
      of the cell type and may be valuable to develop new therapies or as sources of
      active compounds with improved efficacy and selectivity towards OA and IBD.

PMID- 25612778
TI  - Phoenix dactylifera seeds ameliorate early diabetic complications in
      streptozotocin-induced diabetic rats.
AB  - CONTEXT: In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae)
      have been used to manage diabetes for many years. Few studies have reported the
      antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic
      complications is still unexplored. OBJECTIVE: The present study investigates the
      protective effect of P. dactylifera seeds against diabetic complications in rats.
      MATERIAL AND METHODS: The aqueous suspension of P. dactylifera seeds (aqPDS) (1
      g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4
      weeks. The serum biochemical parameters were assessed spectrophotometrically.
      Furthermore, oxidative stress was examined in both liver and kidney tissues by
      assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO),
      reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and
      catalase. RESULTS: Oral administration of aqPDS significantly ameliorated the
      elevated levels of glucose (248 +/- 42 versus 508 +/- 60 mg/dl), urea (32 +/- 3.3
      versus 48.3 +/- 5.6 mg/dl), creatinine (2.2 +/- 0.35 versus 3.8 +/- 0.37 mg/dl),
      ALT (29.6 +/- 3.9 versus 46.4 +/- 5.9 IU/l), and AST (73.3 +/- 13 versus 127.8 +/
      18.7 IU/l) compared with the untreated diabetic rats. In addition to significant
      augmentation in the activities of antioxidant enzymes, there was reduction in
      TBARS and NO levels and improvement of histopathological architecture of the
      liver and kidney of diabetic rats. DISCUSSION AND CONCLUSION: The aqPDS showed
      potential protective effects against early diabetic complications of both liver
      and kidney. This effect may be explained by the antioxidant and free radical
      scavenging capabilities of P. dactylifera seeds.

PMID- 25612779
TI  - Long-term outcome of encapsulating peritoneal sclerosis (EPS) patients in a
      single center.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is the most serious
      complication of peritoneal dialysis (PD) with a high mortality rate. The
      objective of the present study was to determine the clinical characteristics, the
      incidence rate, and the long-term outcome of EPS patients compared with control
      patients. METHODS: Two hundred and seventy patients with end-stage kidney disease
      were started on PD from 1987 to 2013 in the Juntendo University Hospital. EPS was
      diagnosed by clinical findings, radiological findings, and macroscopic inspection
      at the time of laparoscopy or surgical operation. Patient medical records were
      analyzed retrospectively, including clinical characteristics, laboratory
      findings, treatment modality, and outcomes. Using a Kaplan-Meier analysis, we
      compared the survival rate between EPS patients and control PD patients, matched
      for age, gender, diabetes, and duration of PD. RESULTS: Among 270 PD patients, 13
      patients (4.8 %) developed EPS. The mean duration of PD was 120.5 +/- 42.8
      months. There were no significant difference in demographic findings between EPS
      and control PD patients. Among the EPS patients, seven patients died, of which
      four deaths were directly attributed to EPS. All four patients that had had
      surgical enterolysis were doing well and had no recurrences. No significant
      difference in the survival rate between EPS and control PD patients was observed
      in the Kaplan-Meier analysis. CONCLUSIONS: There was no significant difference in
      the survival rate between EPS patients and control PD patients. It appears that
      an early diagnosis by laparoscopy and accurate treatment, including surgical
      enterolysis, might improve mortality.

PMID- 25612780
TI  - Transcriptional regulation of Mcl-1 plays an important role of cellular
      protective effector of vincristine-triggered autophagy in oral cancer cells.
AB  - OBJECTIVE: The autophagy-associated release of HMGB1 (high-mobility group box 1)
      has been reported that protect cancer cells from numerous chemotherapeutics.
      However, the related molecular mechanism involved in the protection of oral
      cancer cells remains unclear. RESEARCH DESIGN AND METHODS: In this study, we
      determined that HMGB1 released by oral cancer cells protected the cells against
      apoptosis caused by vincristine by upregulating the transcription of Mcl-1.
      RESULTS: Extracellular HMGB1 seems to be required for the autophagy-mediated
      inhibition of apoptosis because the effect of autophagy protection was abolished
      by HMGB1 knockdown. Vincristine treatment increased the expression of Mcl-1 mRNA,
      but decreased the Mcl-1 protein expression. HMGB1 expression inhibited blocked
      the Mcl-1 transcription increase and reduced Mcl-1 expression, demonstrate that
      HMGB1 is required for the upregulation of Mcl-1 transcriptional, and thereby
      maintaining Mcl-1 protein expression levels is required for the survival of oral
      cancer cells by vincristine. CONCLUSIONS: Collectively, this study suggested that
      the HMGB1-mediated Mcl-1 transcription upregulation is a key mechanism by which
      autophagy protects oral cancer cells against vincristine-induced apoptosis.

PMID- 25612781
TI  - Evaluation of stem-loop reverse transcription and poly-A tail extension in
      microRNA analysis of body fluids.
AB  - MicroRNA has been demonstrated to be a viable tool for body fluid identification
      purposes in forensic casework. Stem-loop reverse transcription (slRT) is
      regularly used for cDNA synthesis from mature miRNA, along with poly-A tail
      extension. Both have been used in a forensic context, but no direct comparison
      has been carried out. It has also not been shown whether poly-A tail extension
      can be used upon DNA extracts, as previously shown with slRT. Blood and saliva
      samples were collected and underwent DNA extraction with or without on-column DNA
      digestion. All samples were then aliquoted and underwent slRT and poly-A tail
      extension separately. qPCR was then conducted targeting microRNA markers hsa-miR
      451 and hsa-miR-205. It was shown that the DNA digestion step did not affect the
      ability to differentiate between blood and saliva. It was also shown that this
      differentiation was possible using poly-A tail extension, and that poly-A tail
      extension exhibited more amplification than slRT. So whilst the choice of slRT
      and poly-A tail extension for the purpose of forensic body fluid identification
      is not critical, it may be best to use poly-A tail extension, particularly where
      there are low traces of sample. 

PMID- 25612782
TI  - Withdrawn: Formulation and Evaluation of Fast Dissolving Film for Salbutamol
      Sulphate.
AB  - Ahead of Print article withdrawn by publisher

PMID- 25612783
TI  - Maximum bite force following unilateral fixed prosthetic treatment: a within
      subject comparison to the dentate side.
AB  - OBJECTIVES: We evaluated the maximum occlusal bite force (MBF) among individuals
      with fixed partial dentures compared to the opposite dentate side and determined
      the relationship between MBF and gender, age, and body mass index (BMI). SUBJECTS
      AND METHODS: A total of 85 subjects (43 males and 42 females, age range 28-66
      years) with fixed partial dentures on one side and dentate on the other side
      participated in the study. The MBF was measured at the first molar area on both
      sides using a digital hydraulic bite force gauge. The highest MBF value was
      recorded from three measurements of bite force at each side (with 45-second
      intervals between measurements). RESULTS: The mean MBF was 596.2 +/- 76.3 N at
      the dentate side and 580.9 +/- 74.3 N at the fixed partial denture side. The
      difference was statistically significant (p < 0.05). The MBF values were greater
      in males as well as in taller and heavier participants. Nevertheless, the BMI had
      no relationship with MBF values (p >0.05). CONCLUSIONS: Within the same subjects,
      the measured MBF values at the dentate side were higher than those at the fixed
      partial denture side. Females, lighter, and shorter participants had lower MBF
      values. Meanwhile, the BMI had no significant relationship to MBF values.

PMID- 25612784
TI  - A contemporary, single-institutional experience of surgical versus expectant
      management of congenital heart disease in trisomy 13 and 18 patients.
AB  - The objective of this study was to examine a large institutional experience of
      patients with trisomy 13 and trisomy 18 in the setting of comorbid congenital
      heart disease and present the outcomes of surgical versus expectant management.
      It is a retrospective single-institution cohort study. Institutional review board
      approved this study. Thirteen consecutive trisomy 18 patients and three
      consecutive trisomy 13 patients (sixteen patients in total) with comorbid
      congenital heart disease who were evaluated by our institution's Division of
      Cardiovascular Surgery between January 2008 and December 2013 were included in
      the study. The primary outcome measures evaluated were operative mortality (for
      patients who received surgical management), overall mortality (for patients who
      received expectant management), and total length of survival during follow-up. Of
      the thirteen trisomy 18 patients, seven underwent surgical management and six
      received expectant management. With surgical management, operative mortality was
      29 %, and 80 % of patients were alive after a median follow-up of 116 days. With
      expectant management, 50 % of patients died before hospital discharge. Of the
      three patients with trisomy 13, one patient underwent surgical management and two
      received expectant management. The patient who received surgical management with
      complete repair was alive at last follow-up over 2 years after surgery; both
      patients managed expectantly died before hospital discharge. Trisomy 13 and
      trisomy 18 patients with comorbid congenital heart disease can undergo successful
      cardiac surgical intervention. In this population, we advocate that nearly all
      patients with cardiovascular indications for operative congenital heart disease
      intervention should be offered complete surgical repair over palliative
      approaches for moderately complex congenital cardiac anomalies.

PMID- 25612785
TI  - Treatment of pulmonary arterial hypertension using extemporaneous formulation of
      sildenafil in Mexican children.
AB  - Pulmonary arterial hypertension (PAH) is a sickness with high rate of mortality
      that consists of elevation in pressure of the vessels through which blood flows
      to the lung. Sildenafil is a therapeutic option for the treatment of PAH in
      children for the fact that it relaxes the blood vessels and thereby improves
      pulmonary blood flow. The aim was to analyze the clinical behavior of an
      extemporaneous formulation of sildenafil as a therapeutic option in children with
      PAH, twelve children with PAH were studied. The ages and weights of the children
      ranged from 5 to 15 years and from 13 to 27 kg. All patients received a capsule
      of 1 mg/kg of sildenafil prepared as extemporaneous formulation in the
      pharmacology laboratory. Blood levels of sildenafil were analyzed in order to
      evaluate its availability of developed formulation. Management has derived from
      physiopathological knowledge and clinical presentations of patients. The mean
      maximum concentration was 550 ng/ml which is greater than levels reported in
      adults. Moreover, a therapeutic monitoring of sildenafil was carried out in order
      to establish an adequate therapeutic range for children and to show that dosages
      prepared extemporaneously meet the therapeutic needs for the management of PAH.
      With an average follow-up of once every 2 months, it was found that the evolution
      of the patients was favorable and without adverse effects that could put their
      life at risk. The management of PAH with sildenafil prepared as extemporaneous
      formulation might be considered as a good therapeutic option.

PMID- 25612787
TI  - New potential targets for treatment of Cushing's disease: epithelial growth
      factor receptor and cyclin-dependent kinases.
AB  - BACKGROUND: Cushing's disease (CD) is caused by adrenocorticotropic hormone
      (ACTH)-producing pituitary adenomas (ACTHomas). Drug treatment for CD consists of
      three strategies: pituitary tumor-targeted therapy, steroidogenesis inhibitors,
      and glucocorticoid receptor antagonists. All of these strategies are under
      development, and several new drugs have recently been approved for clinical use
      or are being tested in clinical trials. Pituitary-targeted drugs are a
      particularly important method in the treatment of CD. Available pituitary tumor
      targeted drugs include a dopamine receptor agonist and a somatostatin analog.
      Since disrupted cell cycle signaling is clearly associated with pathogenesis of
      ACTHomas which express active forms of epithelial growth factor receptor (EGFR),
      cyclins, and the catalytic subunit of cyclin-dependent kinases (CDKs), we focused
      on these molecules as therapeutic targets for ACTHomas. METHODS: In this review,
      a literature search were performed using PubMed with following terms; Cushing's
      disease, EGFR, CDKs, cell cycle, and targeted therapy. CONCLUSION: Accumulating
      evidence demonstrates that EGFR and cyclin E-CDK2 may be promising targets for
      treating ACTHomas.

PMID- 25612786
TI  - Water distribution in dentin matrices: bound vs. unbound water.
AB  - OBJECTIVE: This work measured the amount of bound versus unbound water in
      completely-demineralized dentin. METHODS: Dentin beams prepared from extracted
      human teeth were completely demineralized, rinsed and dried to constant mass.
      They were rehydrated in 41% relative humidity (RH), while gravimetrically
      measuring their mass increase until the first plateau was reached at 0.064
      (vacuum) or 0.116 gH2O/g dry mass (Drierite). The specimens were then exposed to
      60% RH until attaining the second plateau at 0.220 (vacuum) or 0.191 gH2O/g dry
      mass (Drierite), and subsequently exposed to 99% RH until attaining the third
      plateau at 0.493 (vacuum) or 0.401 gH2O/g dry mass (Drierite). RESULTS: Exposure
      of the first layer of bound water to 0% RH for 5 min produced a -0.3% loss of
      bound water; in the second layer of bound water it caused a -3.3% loss of bound
      water; in the third layer it caused a -6% loss of bound water. Immersion in 100%
      ethanol or acetone for 5 min produced a 2.8 and 1.9% loss of bound water from the
      first layer, respectively; it caused a -4 and -7% loss of bound water in the
      second layer, respectively; and a -17 and -23% loss of bound water in the third
      layer. Bound water represented 21-25% of total dentin water. Chemical dehydration
      of water-saturated dentin with ethanol/acetone for 1 min only removed between 25
      and 35% of unbound water, respectively. SIGNIFICANCE: Attempts to remove bound
      water by evaporation were not very successful. Chemical dehydration with 100%
      acetone was more successful than 100% ethanol especially the third layer of bound
      water. Since unbound water represents between 75 and 79% of total matrix water,
      the more such water can be removed, the more resin can be infiltrated.

PMID- 25612788
TI  - Effectiveness of monetary incentives to recruit family physicians as study
      subjects: a randomized controlled trial.
AB  - BACKGROUND: Recruiting family physicians to participate as subjects of clinical
      studies is challenging. Monetary incentives are often used to increase enrolment,
      but few studies have measured the impact of doing so. As part of a trial seeking
      to compare two formats of interactive activities within an online continuing
      medical education (CME) program, we compared family physicians' recruitment rates
      with and without a monetary incentive. Recruitment took place by email. METHODS:
      Family physicians listed in the directory of the College of Physicians of the
      Province of Quebec (Canada) were emailed a one-page letter inviting them to
      participate in a randomized trial designed to evaluate a three-hour online CME
      program on rheumatology. Half of physicians were randomly allocated to receive a
      version of the letter that offered them $300 to participate (incentive group);
      the other half was not offered compensation (no-incentive group). RESULTS: A
      total of 1314 (91%) physicians had a valid email address as listed in the
      directory. The response rate was 7.5% (54/724) in the incentive group and 2.6%
      (19/724) in the no-incentive group (absolute difference [AD] 4.8%, 95% confidence
      interval [95% CI] = 2.6 - 7.2%; risk ratio [RR] 2.8, 95% CI = 1.7 - 4.7).
      Recruitment rates were 3.5% (25/724) in the incentive group and 0.6% (4/724) in
      the no-incentive group (AD 2.9%, 95% CI = 1.5 - 4.5%; RR 6.3, 95% CI = 2.2 -
      17.9). CONCLUSIONS: Monetary incentives significantly increased recruitment,
      which nonetheless remained low. To reach recruitment targets, researchers are
      advised to plan for an extensive list of email contacts and to minimize
      restrictive eligibility criteria.

PMID- 25612789
TI  - Feasibility and safety of an early discharge strategy after low-risk acute
      myocardial infarction treated with primary percutaneous coronary intervention:
      the EDAMI pilot trial.
AB  - OBJECTIVES: This pilot trial evaluated the feasibility and safety of an early
      discharge strategy (EDS: <=72 h, followed by outpatient lifestyle interventions),
      in comparison with a conventional discharge strategy (CDS) for low-risk (Zwolle
      risk score <=3) ST-elevation myocardial infarction (STEMI) patients treated with
      primary angioplasty. METHODS: One hundred patients were randomized to an EDS (n =
      54) or a CDS (n = 46). The primary end point was the feasibility of the EDS: (1)
      >=70% of EDS patients discharged <=72 h, (2) >=70% visited by a nurse <=7 days
      after discharge, (3) >=70% with >=3 visits by the nurse and (4) >=70% visited by
      a cardiologist <=3 months. RESULTS: The mean age was 59.2 +/- 12.2 years and
      ejection fraction 54.0 +/- 7.1%. Eighty-six percent were male (12% diabetics).
      Vascular access was radial in 91%. Ischemic time was <=4 h in 75%. Length of stay
      was shorter in EDS as compared with CDS (70.1 +/- 8.1 vs. 111.8 +/- 28.3 h, p <
      0.001). EDS feasibility was: (1) 72.2%; (2) 81.5%; (3) 76.9%; (4) 72.2%. There
      were no adverse events or differences in intervention goals and quality of life
      between groups. CONCLUSIONS: An EDS in low-risk STEMI patients is feasible and
      seems to be safe. A shorter hospital stay could benefit patients and health care
      systems.

PMID- 25612790
TI  - [Outcomes of multimorbid vascular surgery patients with and without major
      amputation in a German geriatric rehabilitation clinic].
AB  - BACKGROUND: In the course of demographic developments, an increase of vascular
      surgical procedures including major amputations in very elderly, multimorbid
      geriatric patients is expected. Due to the high vulnerability of these patients,
      geriatric rehabilitation directly following the acute inpatient treatment is
      likely to improve the abilities of these patients. This issue is not well
      analyzed in Germany up to now. MATERIALS AND METHODS: This retrospective study
      includes all patients who were admitted to our clinic for geriatric
      rehabilitation after vascular surgery between 01 June 2012 and 31 December 2013.
      Geriatric assessments at the time of admission and discharge were considered. The
      group was divided into rehabilitation patients with major limb amputation and
      nonmajor limb amputation. Both groups were analyzed with respect to functional
      parameters and activities in daily life (ADL) during the course of rehabilitation
      as well as the discharge location (home versus nursing home). RESULTS: A total of
      30 major-limb-amputee and 77 nonmajor-limb-amputee rehabilitants could be
      analyzed. Before surgical intervention, 100  % of patients lived in a home care
      situation. The median age was 78.3 years. During rehabilitation, both groups
      showed highly significant improvements in ADL (Barthel index), Timed Up and Go
      test, walking distance, and stair climbing; however the nonmajor amputees
      surpassed the major amputees in most mobility assessments especially in the five
      chair-rising test. The rehabilitation time (median) was 41.8 days for major and
      23.9 days for nonmajor amputees. More than 90  % of the rehabilitants in both
      groups could be discharged home. CONCLUSION: The data from this retrospective
      study indicate that even advanced old age, multimorbid patients benefit from
      geriatric rehabilitation after vascular surgery intervention. Although less
      distinct than the group of minor amputee rehabilitants, highly significant
      improvements were also demonstrated in the group of major amputee rehabilitants
      as assessed in the discharge mobility and ADL results compared to the admission
      assessment results. These improvements were achieved in an adequate time period
      and led to discharge into home care for the majority of patients.

PMID- 25612792
TI  - Organizational decision to adopt hospital information system: an empirical
      investigation in the case of Malaysian public hospitals.
AB  - OBJECTIVES: This study mainly integrates the mature Technology-Organization
      Environment (TOE) framework and recently developed Human-Organization-Technology
      (HOT) fit model to identify factors that affect the hospital decision in adopting
      Hospital Information System (HIS). METHODS: Accordingly, a hybrid Multi-Criteria
      Decision-Making (MCDM) model is used to address the dependence relationships of
      factors with the aid of Analytic Network Processes (ANP) and Decision Making
      Trial and Evaluation Laboratory (DEMATEL) approaches. The initial model of the
      study is designed by considering four main dimensions with 13 variables as
      organizational innovation adoption factors with respect to HIS. By using DEMATEL,
      the interdependencies strength among the dimensions and variables are tested. The
      ANP method is then adopted in order to determine the relative importance of the
      adoption factors, and is used to identify how these factors are weighted and
      prioritized by the public hospital professionals, who are wholly familiar with
      the HIS and have years of experience in decision making in hospitals' Information
      System (IS) department. RESULTS: The results of this study indicate that from the
      experts' viewpoint "Perceived Technical Competence" is the most important factor
      in the Human dimension. In the Technology dimension, the experts agree that the
      "Relative Advantage" is more important in relation to the other factors. In the
      Organization dimension, "Hospital Size" is considered more important rather than
      others. And, in the Environment dimension, according to the experts judgment,
      "Government Policy" is the most important factor. The results of ANP survey from
      experts also reveal that the experts in the HIS field believed that these factors
      should not be overlooked by managers of hospitals and the adoption of HIS is more
      related to more consideration of these factors. In addition, from the results, it
      is found that the experts are more concerned about Environment and Technology for
      the adoption HIS. CONCLUSIONS: The findings of this study make a novel
      contribution in the context of healthcare industry that is to improve the
      decision process of innovation in adoption stage and to help enhance more the
      diffusion of IS in the hospital setting, which by doing so, can provide plenty of
      profits to the patient community and the hospitals.

PMID- 25612791
TI  - Usability and feasibility of a tablet-based Decision-Support and Integrated
      Record-keeping (DESIRE) tool in the nurse management of hypertension in rural
      western Kenya.
AB  - BACKGROUND: Mobile health (mHealth) applications have recently proliferated,
      especially in low- and middle-income countries, complementing task-redistribution
      strategies with clinical decision support. Relatively few studies address
      usability and feasibility issues that may impact success or failure of
      implementation, and few have been conducted for non-communicable diseases such as
      hypertension. OBJECTIVE: To conduct iterative usability and feasibility testing
      of a tablet-based Decision Support and Integrated Record-keeping (DESIRE) tool, a
      technology intended to assist rural clinicians taking care of hypertension
      patients at the community level in a resource-limited setting in western Kenya.
      METHODS: Usability testing consisted of "think aloud" exercises and "mock patient
      encounters" with five nurses, as well as one focus group discussion. Feasibility
      testing consisted of semi-structured interviews of five nurses and two members of
      the implementation team, and one focus group discussion with nurses. Content
      analysis was performed using both deductive codes and significant inductive
      codes. Critical incidents were identified and ranked according to severity. A
      cause-of-error analysis was used to develop corresponding design change
      suggestions. RESULTS: Fifty-seven critical incidents were identified in usability
      testing, 21 of which were unique. The cause-of-error analysis yielded 23 design
      change suggestions. Feasibility themes included barriers to implementation along
      both human and technical axes, facilitators to implementation, provider issues,
      patient issues and feature requests. CONCLUSIONS: This participatory, iterative
      human-centered design process revealed previously unaddressed usability and
      feasibility issues affecting the implementation of the DESIRE tool in western
      Kenya. In addition to well-known technical issues, we highlight the importance of
      human factors that can impact implementation of mHealth interventions.

PMID- 25612793
TI  - Contrast-free diagnosis and treatment of coronary artery disease guided by
      integrated cardiac imaging: concept and first clinical experience.
AB  - The use of iodinated contrast media (ICM) remains a potential hazard for patients
      undergoing diagnostic cardiac imaging and percutaneous coronary intervention. In
      particular patients with history of prior adverse reaction to a contrast agent
      are at a high risk in case of re-exposure, even if designated premedication is
      administered. Based on a patient with recurrent angina pectoris and history of
      systemic anaphylactic reaction to ICM, we describe the logical stepwise approach
      from diagnostic imaging to safe and successful imaging guided percutaneous
      coronary intervention without the use of contrast agent. 

PMID- 25612794
TI  - The Internalized Stigma of Mental Illness: Cross-Cultural Adaptation and
      Psychometric Properties of the Portuguese Version of the ISMI Scale.
AB  - This study examined the psychometric properties of the Portuguese version of the
      ISMI scale in a sample of 253 adult psychiatric outpatients. The exploratory
      factor analysis replicated the five factor structure of the scale. The results
      revealed good internal consistency. Criterion-related validity supported the
      variability in response to stigma across clinical diagnoses. Thus, the Portuguese
      version of the ISMI scale can be considered appropriate to measure and
      differentiate between stigmatization experiences. Also, in order to design more
      focused approaches aimed to reduce the negative effects of internalized stigma,
      its use in institutional and in community-based mental health services is
      recommended. 

PMID- 25612795
TI  - Moderators of the response to a nurse-led psychosocial intervention to reduce
      depressive symptoms in head and neck cancer patients.
AB  - PURPOSE: Little is known about the variables that moderate the response to
      psychosocial interventions to decrease depressive symptoms in cancer patients.
      The purpose of this study was to determine whether variables associated with
      depressive symptoms in cancer patients in general moderate the response to a
      nurse-led psychosocial intervention in patients with head and neck cancer.
      METHODS: This study is a secondary analysis of a randomized controlled trial
      evaluating the effect of the nurse counseling and after intervention (NUCAI) on
      depressive symptoms 12 months after cancer treatment in patients with head and
      neck cancer. Of 205 patients, 103 received the NUCAI and 102 care as usual.
      Twenty-one variables were selected for analysis and a linear regression analyses
      including interaction terms was performed for each variable separately.
      Significant moderators were post hoc probed. RESULTS: Four moderators were found:
      marital status, global quality of life, emotional functioning, and social
      functioning. Patients who were married/living together or had low scores for
      global quality of life, and emotional or social functioning at baseline benefited
      more from the NUCAI than patients who were single or with high scores for global
      quality of life and emotional or social functioning. CONCLUSIONS: Marital status,
      global quality of life, and emotional and social functioning of head and neck
      cancer patients should be evaluated to determine whether they might benefit from
      a psychosocial intervention to combat depressive symptoms. Further research is
      necessary to replicate results and to contribute to the knowledge needed to make
      screening and personalized patient care possible.

PMID- 25612796
TI  - Reduced prescribing of benzodiazepines in Denmark and Norway.

PMID- 25612799
TI  - The Therapeutic Efficacy of Domestic Violence Victim Interventions.
AB  - A meta-analysis on domestic violence interventions was conducted to determine
      overall effectiveness of mental health programs involving women and children in
      joint treatment. These interventions were further analyzed to determine whether
      outcomes are differentially affected based on the outcome measure employed. To
      date, no meta-analyses have been published on domestic violence victim
      intervention efficacy. The 17 investigations that met study criteria yielded
      findings indicating that domestic violence interventions have a large effect size
      (d = .812), which decreases to a medium effect size when compared to control
      groups (d = .518). Effect sizes were assessed to determine whether treatment
      differed according to the focus of the outcome measure employed: (a) external
      stress (behavioral problems, aggression, or alcohol use); (b) psychological
      adjustment (depression, anxiety, or happiness); (c) self-concept (self-esteem,
      perceived competence, or internal locus of control); (d) social adjustment
      (popularity, loneliness, or cooperativeness); (e) family relations (mother-child
      relations, affection, or quality of interaction); and (f) maltreatment events
      (reoccurrence of violence, return to partner). Results reveal that domestic
      violence interventions across all outcome categories yield effects in the medium
      to large range for both internalized and externalized symptomatology.
      Implications for greater awareness and support for domestic violence treatment
      and programming are discussed. 

PMID- 25612797
TI  - Maternal influences over offspring allergic responses.
AB  - Asthma occurs as a result of complex interactions of environmental and genetic
      factors. Clinical studies and animal models of asthma indicate offspring of
      allergic mothers have increased risk of development of allergies. Environmental
      factors including stress-induced corticosterone and vitamin E isoforms during
      pregnancy regulate the risk for offspring development of allergy. In this review,
      we discuss mechanisms for the development of allergic disease early in life,
      environmental factors that may impact the development of risk for allergic
      disease early in life, and how the variation in global prevalence of asthma may
      be explained, at least in part, by some environmental components. 

PMID- 25612798
TI  - Rhinovirus and asthma: a storied history of incompatibility.
AB  - The human rhinovirus (HRV) is commonly associated with loss of asthma symptom
      control requiring escalation of care and emergency room visits in many patients.
      While the association is clear, the mechanisms behind HRV-induced asthma
      exacerbations remain uncertain. Immune dysregulation via aberrant immune
      responses, both deficient and exaggerated, have been proposed as mechanisms for
      HRV-induced exacerbations of asthma. Epithelium-derived innate immune cytokines
      that bias Th2 responses, including interleukin (IL)-25, IL-33, and thymic stromal
      lymphopoietin (TSLP), have also been implicated as a means to bridge allergic
      conditions with asthma exacerbations. In this review, we discuss the literature
      supporting these positions. We also discuss new and emerging biotherapeutics that
      may target virus-induced exacerbations of asthma. 

PMID- 25612800
TI  - An Examination of the Gender Inclusiveness of Current Theories of Sexual Violence
      in Adulthood: Recognizing Male Victims, Female Perpetrators, and Same-Sex
      Violence.
AB  - Although the majority of adulthood sexual violence involves a male perpetrator
      and a female victim, there is also substantial evidence that members of both
      genders can be victims and perpetrators of sexual violence. As an alternative to
      viewing sexual violence within gender-specific terms, we advocate for the use of
      a gender inclusive conceptualization of sexual aggression that takes into account
      the factors that contribute to sexual victimization of, and victimization by,
      both men and women. The goal of the current review is to examine the need and
      importance of a gender inclusive conceptualization of sexual violence and to
      discuss how compatible our current theories are with this conceptualization.
      First, we examine evidence of how a gender-specific conceptualization of sexual
      violence aids in obscuring assault experiences that are not male to female and
      how this impacts victims of such violence. We specifically discuss this impact
      regarding research, law, public awareness, advocacy, and available victim
      treatment and resources. Next, we provide an overview of a number of major sexual
      violence theories that are relevant for adult perpetrators and adult victims,
      including neurobiological and integrated biological theories, evolutionary
      psychology theory, routine activity theory, feminist theory, social learning and
      related theories, typology approaches, and integrated theories. We critically
      examine these theories' applicability to thinking about sexual violence through a
      gender inclusive lens. Finally, we discuss further directions for research,
      clinical interventions, and advocacy in this area. Specifically, we encourage
      sexual violence researchers and clinicians to identify and utilize appropriate
      theoretical frameworks and to apply these frameworks in ways that incorporate a
      full range of sexual violence. 

PMID- 25612801
TI  - Comic strips help children understand medical research: targeting the informed
      consent procedure to children's needs.
AB  - OBJECTIVE: Children involved in medical research often fail to comprehend
      essential research aspects. In order to improve information provision, a
      participatory approach was used to develop new information material explaining
      essential concepts of medical research. METHODS: A draft of a comic strip was
      developed by a science communicator in collaboration with pediatricians. The
      draft was presented to children participating in a clinical trial and to two
      school classes. Children were consulted for further development in surveys and
      interviews. Subsequently, the material was revised and re-evaluated in four
      school classes with children of varying ages and educational levels. RESULTS: In
      the first evaluation, children provided feedback on the storyline, wording and
      layout. Children thought the comic strip was 'fun' and 'informative'.
      Understanding of 8 basic research aspects was on average 83% and all above 65%,
      illustrating that children understood and remembered key messages. CONCLUSION: A
      comic strip was developed to support the informed consent process. Children were
      consulted and provided feedback. The resulting material was well understood and
      accepted. PRACTICE IMPLICATIONS: Involving children in the development of
      information material can substantially contribute to the quality of the material.
      Children were excited to participate and to 'be a part of science'.

PMID- 25612802
TI  - Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell
      and small cell lung cancer models.
AB  - BACKGROUND: Carfilzomib (CFZ) is a proteasome inhibitor that selectively and
      irreversibly binds to its target and has been approved in the US for treatment of
      relapsed and refractory multiple myeloma. Phase 1B studies of CFZ reported
      signals of clinical activity in solid tumors, including small cell lung cancer
      (SCLC). The aim of this study was to investigate the activity of CFZ in lung
      cancer models. METHODS: A diverse panel of human lung cancer cell lines and a
      SHP77 small cell lung cancer xenograft model were used to investigate the anti
      tumor activity of CFZ. RESULTS: CFZ treatment inhibited both the constitutive
      proteasome and the immunoproteasome in lung cancer cell lines. CFZ had marked
      anti-proliferative activity in A549, H1993, H520, H460, and H1299 non-small cell
      lung cancer (NSCLC) cell lines, with IC50 values after 96 hour exposure from <1.0
      nM to 36 nM. CFZ had more variable effects in the SHP77 and DMS114 SCLC cell
      lines, with IC50 values at 96 hours from <1 nM to 203 nM. Western blot analysis
      of CFZ-treated H1993 and SHP77 cells showed cleavage of poly ADP ribose
      polymerase (PARP) and caspase-3, indicative of apoptosis, and induction of
      microtubule-associated protein-1 light chain-3B (LC3B), indicative of autophagy.
      In SHP77 flank xenograft tumors, CFZ monotherapy inhibited tumor growth and
      prolonged survival, while no additive or synergistic anti-tumor efficacy was
      observed for CFZ + cisplatin (CDDP). CONCLUSIONS: CFZ demonstrated anti
      proliferative activity in lung cancer cell lines in vitro and resulted in a
      significant survival advantage in mice with SHP77 SCLC xenografts, supporting
      further pre-clinical and clinical investigations of CFZ in NSCLC and SCLC.

PMID- 25612804
TI  - Modification of chimeric (2S, 3S)-butanediol dehydrogenase based on structural
      information.
AB  - A chimeric (2S, 3S)-butanediol dehydrogenase (cLBDH) was engineered to have the
      strict (S)-configuration specificity of the (2S, 3S)-BDH (BsLBDH) derived from
      Brevibacterium saccharolyticum as well as the enzymatic stability of the (2R, 3S)
      BDH (KpMBDH) from Klebsiella pneumonia by swapping the domains of two native
      BDHs. However, while cLBDH possesses the stability, it lacks the specificity. In
      order to assist in the design a BDH having strict substrate specificity, an X-ray
      structural analysis of a cLBDH crystal was conducted at 1.58 A. The results
      obtained show some readily apparent differences around the active sites of cLBDH
      and BsLBDH. Based on this structural information, a novel (2S, 3S)-BDH having a
      preferred specificity was developed by introducing a V254L mutation into cLBDH.
      The influence of this mutation on the stability of cLBDH was not evaluated.
      Nevertheless, the technique described herein is an effective method for the
      production of a tailor-made BDH. 

PMID- 25612803
TI  - Weight loss intention, dietary behaviors, and barriers to dietary change in
      veterans with lower extremity amputations.
AB  - BACKGROUND: Obesity is thought to be highly prevalent in persons with lower
      extremity amputations (LEAs) and can impair physical and social functioning.
      OBJECTIVE: The aim of this study was to determine the prevalence of weight loss
      intention, weight loss strategies, dietary patterns, and barriers to making
      dietary changes, and their associations with body mass index (BMI, kg/m(2)),
      amputation characteristics, health status, and socioeconomic factors. METHODS: We
      conducted a cross-sectional study (n = 150) using data from a self-administered
      questionnaire. RESULTS: 43% of participants were obese and 48% were trying to
      lose weight; 83% of those trying to lose weight reported trying to "eat
      differently", but only 7% were following a comprehensive weight loss program
      involving dietary changes, physical activity, and behavioral counseling. 21% of
      participants reported >= 6 barriers to changing their eating habits (e.g., habit,
      too little money, stress/depression). Obesity was associated with younger age,
      lower physical health scores, hypertension, arthritis, and diabetes. Compared to
      those not trying to lose weight, a greater proportion of those trying to lose
      weight had a BMI >= 35 kg/m(2), age <55 years, higher physical and mental health
      scores, and more frequent consumption of vegetables, beans, chicken, and fish.
      CONCLUSIONS: Though over half of overweight and obese individuals with LEA were
      trying to lose weight, few reported following a comprehensive program to lose
      weight, which may indicate an unmet need for services for this group. To be
      effective, these programs will need to address the complex physical and mental
      health challenges that many of these individuals face.

PMID- 25612806
TI  - Percutaneous drainage for afferent limb syndrome and pancreatic fistula via the
      blind end of the jejunal limb after pancreatoduodenectomy or bile duct resection.
AB  - PURPOSE: To investigate the feasibility of percutaneous drainage via the blind
      end of the jejunal limb (BEJL) for afferent limb syndrome and pancreatic fistula.
      MATERIALS AND METHODS: Percutaneous drainage via the BEJL was performed in eight
      patients (seven men and one woman; mean age, 63 y; range, 42-71 y) presenting
      with afferent limb syndrome (n = 6) or pancreatic fistula (n = 2) following
      pancreatoduodenectomy or bile duct resection with reconstruction at our institute
      from March 2005 to June 2013. Reconstruction was performed by using a modified
      Child method or the Roux-en-Y method, and the BEJL was surgically fixed to the
      abdominal wall. Afferent limb syndrome was caused by tumor recurrence or
      postoperative complications. Technical success, clinical success, and
      complications were evaluated retrospectively. RESULTS: Technical success of
      drainage via BEJL was achieved in all patients. Drainage catheters (5-10 F) were
      inserted into the afferent limbs of six patients, into the pancreatic duct of one
      patient, and into the pancreatic fistula of one patient. Metallic stents were
      subsequently placed to address malignant afferent limb obstruction in two
      patients. Clinical success was achieved in seven patients (87.5%), and no
      patients developed major complications. Drainage catheters were removed from four
      patients. The mean catheter indwelling period in all patients was 143 days
      (range, 21-292 d). CONCLUSIONS: Percutaneous drainage via BEJL after
      pancreatoduodenectomy or bile duct resection may be a feasible treatment for
      afferent limb syndrome and pancreatic fistula.

PMID- 25612807
TI  - Comparison of chemoembolization with and without radiation therapy and sorafenib
      for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a
      propensity score analysis.
AB  - PURPOSE: To compare efficacy of transarterial chemoembolization with and without
      radiation therapy (RT) versus sorafenib for advanced hepatocellular carcinoma
      (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: This
      single-center retrospective study involved 557 patients with HCC with PVTT who
      initially received chemoembolization (1997-2002; n = 295), chemoembolization and
      RT (2003-2008; n = 196), or sorafenib (2009-2012; n = 66) according to
      eligibility criteria among an initial population of 617. The three groups were
      divided into three pairs (chemoembolization vs chemoembolization/RT,
      chemoembolization vs sorafenib, and chemoembolization/RT vs sorafenib), and time
      to progression (TTP) and overall survival (OS) were compared by propensity-score
      analyses. RESULTS: The chemoembolization/RT group had longer median TTP and OS
      than the chemoembolization-alone and sorafenib groups (P < .001). Multivariate
      Cox analysis revealed that chemoembolization/RT treatment was an independent
      predictor of favorable TTP and OS. In the matched cohort, median TTP and OS were
      significantly longer in the chemoembolization/RT group than the chemoembolization
      alone group (102 pairs; TTP, 8.7 mo vs 3.6 mo [P < .001]; OS, 11.4 mo vs 7.4 mo
      [P = .023]) or the sorafenib group (30 pairs; TTP, 5.1 mo vs 1.6 mo [P < .001];
      OS, 8.2 mo vs 3.2 mo [P < .001]), in agreement with the inverse probability of
      treatment weighted (IPTW) outcomes. In matching analyses, the chemoembolization
      alone group had longer median TTP and OS than the sorafenib group (46 pairs; TTP,
      3.4 mo vs 1.8 mo [P < .001]; OS, 5.9 mo vs 4.4 mo [P = .003]). There was no
      significant difference in terms of OS with the IPTW approach (P = .108), but
      there was one in terms of TTP (P < .001). CONCLUSIONS: Within the limitation of a
      retrospective study, the present data indicate that transarterial
      chemoembolization combined with RT could be considered as an alternative to the
      standard sorafenib in the treatment of patients with advanced-stage HCC with
      PVTT.

PMID- 25612805
TI  - A novel inhaled multi-pronged attack against respiratory bacteria.
AB  - Airway mucus hypersecretion is a common clinical feature of many severe
      respiratory diseases, and when complicated by a recalcitrant bacterial infection,
      the whole treatment regimen thereby becomes more challenging and protracted. The
      accumulation of thickened mucus secretions in the lower airways provides a
      nutrient-rich breeding ground for bacteria that promotes their growth and limits
      the ease of effective eradication. Unfortunately, no direct-inhaled dry powder
      formulation to treat these respiratory mucoid infections more effectively is
      available commercially. This work therefore seeks to develop a highly-efficacious
      ternary dry powder inhaler (DPI) formulation (ciprofloxacin hydrochloride (CIP),
      gatifloxacin hydrochloride (GAT) and ambroxol hydrochloride (AMB)) capable of
      delivering a novel multi-pronged attack (synergy, quorum quenching and
      mucociliary clearance) on Pseudomonas aeruginosa, a common respiratory bacteria
      found in mucoid infections. The powders were prepared via spray drying, evaluated
      on their aerosol performance via a multi-stage liquid impinger (MSLI) and tested
      for their efficacies in bacteria-spiked artificial sputum medium (ASM). The
      optimized particles were of respirable-size (d50 of ~1.61+/-0.03MUm) and slightly
      corrugated. When dispersed via an Aerolizer(r) inhaler at 60L/min, the powder
      showed concomitant in vitro deposition, minimal capsule, device and throat
      retention, and highly promising and uniform fine particle fractions (of the
      loaded dose) of ~64-69%, which was a vast improvement over the singly-delivered
      actives. Favourably, when tested on bacteria-spiked ASM, the optimized ternary
      formulation (with AMB) was more effective at killing bacteria (i.e. faster rate
      of killing) than just the synergistic antibiotics alone (binary formulation;
      without AMB). In conclusion, a ternary antibiotic-(non-antibiotic) DPI
      formulation involving a unique multi-pronged attack mechanism was successfully
      pioneered and optimized for mucoid infections. 

PMID- 25612808
TI  - Long-term survival following percutaneous radiofrequency ablation of colorectal
      lung metastases.
AB  - PURPOSE: To retrospectively evaluate long-term survival outcomes of
      radiofrequency (RF) ablation of colorectal lung metastases and evaluate factors
      associated with improved survival. MATERIALS AND METHODS: Eighty-four patients
      (46 male and 38 female; median age, 65 y) with 172 colorectal lung metastases
      (median size, 1.2 cm) underwent 113 RF ablation sessions. Thirteen patients had
      viable extrapulmonary recurrences at the time of RF ablation. The primary
      endpoint was patient survival. Prognostic factors associated with survival were
      determined by univariate and multivariate analyses. Secondary endpoints were
      local tumor progression and adverse events (per National Cancer Institute Common
      Terminology Criteria for Adverse Events, version 4.0). RESULTS: During follow-up
      (median duration, 37.5 mo), 36 patients (42.9%) died. The estimated overall
      survival (OS) rates were 95.2%, 65.0%, and 51.6% at 1, 3, and 5 years,
      respectively (median OS time, 67.0 mo). Multivariate analysis revealed that a
      carcinoembryonic antigen (CEA) level of at least 5 ng/mL before RF ablation (P =
      .03) and the presence of viable extrapulmonary recurrences at the time of RF
      ablation (P = .001) were independent negative prognostic factors. The local tumor
      progression rate was 14.0% (24 of 172 tumors). Grade 3 adverse events were
      observed after two sessions (1.8%), and grade 4/5 adverse events were not
      observed. CONCLUSIONS: RF ablation of colorectal lung metastases provided
      favorable long-term survival with a low incidence of severe adverse events.
      Independent prognostic factors were a high CEA level before RF ablation and the
      presence of viable extrapulmonary recurrences at the time of RF ablation.

PMID- 25612811
TI  - [The progressive reduction of functioning in the course of mucopolysaccharidosis
      type IIIA - longitudinal study of two siblings].
AB  - INTRODUCTION: This paper presents a description of changes in the functioning of
      two siblings diagnosed with mucopolysaccharidosis type III A. Both are under
      specialist care exercised by the Rehabilitation, Care and Education Centre in the
      city Kielce, including care of a oligophrenopedagogue, a psychologist, a speech
      therapist and a physiotherapist. AIM OF THE STUDY: Evaluation of changes in
      functioning of two siblings diagnosed with mucopolysaccharidosis type IIIA.
      MATERIAL AND METHODS: The longitudinal study covered two children with MPS type
      IIIA. During the 29 months of observation, there were six measurements on the
      basis of PPAC Gunzburg Inventory in the Polish adaptation by Tadeusz Witkowski.
      The results are shown in the form of PPAC diagrams and profiles of functioning.
      RESULTS: Despite the differences in the presence and severity of somatic and
      neurocognitive symptoms, functioning both of the boy and the girl does not differ
      from functioning described in the literature. Therapeutic interventions have
      produced short-term improvements in its area of self-service, communication and
      activities. CONCLUSIONS: Despite the similar trend of changes in functioning,
      there is an inter-individual variability in the quality of patterns and dynamics
      of progress. The progressive decrease in the level of functioning in patients
      with MPS IIIA does not preclude the acquisition of new skills. They are not
      permanent, however. There is a need for functional assessment in order to learn
      more about the specificity of the disease and to assume an individualised
      therapeutic approach aimed at improving the quality of life of patients with MPS
      IIIA and, indirectly, the quality of life of their families.

PMID- 25612812
TI  - Symmetry and asymmetry of reaction time and body tissue composition of upper
      limbs in young female basketball players.
AB  - INTRODUCTION: The role of psychomotor abilities and their relationship to the
      morphofunctional characteristics of athletes is becoming more and more emphasized
      in studies on the subject, especially for disciplines that require athletes to
      notice and to respond to signals originating in dynamically changing conditions.
      At the same time, athletes who perform symmetrically are more effective and less
      likely to sustain an injury through unilateral strain. AIM OF THE STUDY:
      Assessment of the degree of symmetry and asymmetry of reaction time to stimuli in
      the central and peripheral visual fields, and assessment of body composition of
      upper limbs in young female basketball players. MATERIAL AND METHODS:
      Participants of the study comprised 17 young female basketball players. Their
      average age was 18.11-0.8 years. On average, they had been training basketball
      for 6.83-1.75 years. Body tissue composition was measured using the bioelectrical
      impedance method. The degree of symmetry and asymmetry of reaction time to
      signals in the central and peripheral visual fields were measured using the
      Reaction Test (RT-S1) and a modified Peripheral Perception (PP) test within the
      Vienna Test System. RESULTS: An analysis of body tissue composition of the upper
      right and upper left limbs found an asymmetry (p<0.01 and p<0.05) in the FAT [%],
      FAT MASS [kg], and FFM [kg] parameters. The values of these parameters were
      higher for the non-dominant arm. No statistically significant differences were
      found in reaction time and motor time for the dominant and non-dominant arm. A
      correlation was found between motor time and the FFM [kg] (r=-0.62; p<0.05) and
      PMM [kg] (r=-0.63; p<0.05) parameters. CONCLUSIONS: A significant asymmetry was
      found in the body tissue composition of the upper limbs. Asymmetry of reaction
      time was found only for signals in the peripheral visual field.

PMID- 25612810
TI  - Radiation therapy in pediatric pineal tumors.
AB  - Pineal tumor management in pediatric patients must be based on close co-operation
      between oncologists, surgeons, radiation oncologists, neurologists,
      ophthalmologists, and endocrinologists. Radiation therapy (RT) remains critical
      in most situations and should be assessed as soon as the diagnosis is made, in
      order to optimize the radiation technique. This paper will focus on RT
      modalities, indications, as well as modalities in main pediatric pineal tumors
      (germ cell tumors and pineal parenchyma tumors). RT modalities are presently
      being debated and new RT techniques (intensity-modulated RT, proton therapy etc.)
      that are now available for pineal lesions need to be evaluated. Radiation
      strategies are also controversial for germ cell tumors: cranio-spinal radiation
      versus chemotherapy followed by focal radiation, which also requires discussion. 

PMID- 25612813
TI  - [Epidemiology and clinical course of diabetic ketoacidosis in children and
      adolescents with type 1 diabetes mellitus].
AB  - INTRODUCTION: Despite the progress in diagnosis and treatment of type 1 diabetes,
      diabetic ketoacidosis (DKA) is still a serious clinical problem. The aim of the
      study was too describe the epidemiology and clinical characteristic of DKA in
      children and adolescents with type 1 diabetes. MATERIAL AND METHODS: Medical
      records of 650 patients with type 1 diabetes who were under care of the
      Outpatient Clinic for Diabetic Children of the Medical University of Lodz from
      1st January 2007 till 31 December 2009 were analysed. RESULTS: 101 cases of DKA
      were reported; the incidence of DKA was 5.2/100 patients /year. Episodes of DKA
      occurred in 89 patients (39 girls and 50 boys). In 82 patients 1 episode of DKA
      was recorded, in 3 patients - 2 episodes, in 3 patients - 3 episodes and in 1
      patient - 4 episodes. 58.4% (59/101) of DKA episodes occurred in patients with
      newly diagnosed diabetes (mean age: 8.04-4.78 years) and 41.6% (42/101) - in
      children with established type 1 diabetes (mean age: 13.3-3.37). DKA was
      diagnosed in 26,1% of children with new onset of the disease. The most frequent
      causes of DKA in patients with established type 1 diabetes were noncompliance
      (22/42) and acute infectious diseases (12/42). Severe DKA was diagnosed in 19/101
      episodes, moderate - in 36/101 and mild - in 46/101. No lethal complication of
      DKA was recorded. The following complications of DKA were observed:
      dyselectrolitemia (68/101), acute pancreatitis (5/101), gastrorrhagia (1/101),
      insulin oedema (1/101). Mean duration of hospitalization was 12.03-5.58 days.
      CONCLUSIONS: Newly diagnosed type 1 diabetes is the main cause of DKA in children
      and adolescents.In established type 1 diabetes the most frequent cause of DKA is
      poor quality of self-management. Dyselectrolitemia is the most frequent
      complication of DKA in children. Acute pancreatitis should be considered in a
      young patient with DKA.

PMID- 25612809
TI  - Genome-wide high-resolution mapping of DNA methylation identifies epigenetic
      variation across embryo and endosperm in Maize (Zea may).
AB  - BACKGROUND: Epigenetic modifications play important roles in plant and animal
      development. DNA methylation impacts the transposable element (TE) silencing,
      gene imprinting and expression regulation. RESULTS: Through a genome-wide
      analysis, DNA methylation peaks were characterized and mapped in maize embryo and
      endosperm genome, respectively. Distinct methylation level was observed across
      maize embryo and endosperm. The maize embryo genome contained more DNA
      methylation than endosperm. Totally, 985,478 CG islands (CGIs) were identified
      and most of them were unmethylated. More CGI shores were methylated than CGIs in
      maize suggested that DNA methylation level was not positively correlated with CpG
      density. The promoter sequence and transcriptional termination region (TTR) were
      more methylated than the gene body (intron and exon) region based on peak number
      and methylated depth. Result showed that 99% TEs were methylated in maize embryo,
      but a large portion of them (34.8%) were not methylated in endosperm. Maize
      embryo and endosperm exhibit distinct pattern/level of methylation. The most
      differentially methylated region between embryo and endosperm are CGI shores. Our
      results indicated that DNA methylation is associated with both gene silencing and
      gene activation in maize. Many genes involved in embryogenesis and seed
      development were found differentially methylated in embryo and endosperm. We
      found 41.5% imprinting genes were similarly methylated and 58.5% imprinting genes
      were differentially methylated between embryo and endosperm. Methylation level
      was associated with allelic silencing of only a small number of imprinting genes.
      The expression of maize DEMETER-like (DME-like) gene and MBD101 gene (MBD4
      homolog) were higher in endosperm than in embryo. These two genes may be
      associated with distinct methylation levels across maize embryo and endosperm.
      CONCLUSIONS: Through MeDIP-seq we systematically analyzed the methylomes of maize
      embryo and endosperm and results indicated that the global methylation status of
      embryo was more than that of the endosperm. Differences could be observed at the
      total number of methylation peaks, DMRs and specific methylated genes which were
      tightly associated with development of embryo and endosperm. Our results also
      revealed that many DNA methylation regions didn't affect transcription of the
      corresponding genes.

PMID- 25612814
TI  - [Frequency and clinical manifestation of diabetic ketoacidosis in children with
      newly diagnosed type 1 diabetes].
AB  - INTRODUCTION: Diabetic ketoacidosis (DKA) is still the most dangerous acute
      complication of type 1 diabetes mellitus (T1DM). It is a life-threatening
      condition requiring intensive treatment. DKA may be the first symptom of
      previously undiagnosed diabetes, especially in children. AIM OF THE STUDY:
      Assessment of the incidence and clinical manifestation of diabetic ketoacidosis
      in children with newly diagnosed type 1 diabetes. MATERIAL AND METHODS: We
      analyzed 535 medical files of children (aged 9 months to 17 years, mean age 4.41
      9.96, 261 girls (48%)) hospitalized from 2006 to 2009 because of the newly
      diagnosed type 1 diabetes mellitus. DKA was diagnosed (according to ISPAD) in
      children with pH <7.3, blood glucose level >11 mmol/L (>200 mg/dL) and/or blood
      concentration of bicarbonate <15 mmol/L with ketonuria. Severe DKA was diagnosed
      in children with pH <7.2. RESULTS: DKA was diagnosed in 123 patients (23%) (63
      girls (51%)). The mean age of children with DKA was significantly lower than the
      age of the children without DKA (9.05-4.45 vs 9.48-4.39 years; p<0.001). Mean pH
      was 7.21-1.03 (min. 6,82; max. 7,30). In 32.5% of children with DKA severe
      ketoacidosis (pH -7.2) was observed. The prevalence of acidosis was higher in the
      0-4 age group compared to children over 4 years (28 vs. 22%, p<0.001). Neither
      sex, nor symptoms duration were associated with the development of DKA. Polyuria
      (95%), polydipsia (95%), weight loss (85%) and abdominal pain (50%) were the most
      common symptoms reported by patients. CONCLUSIONS: Despite the typical
      symptomatology of type 1 diabetes mellitus, about 1/4 of newly diagnosed diabetes
      in children is accompanied by ketoacidosis. The risk of acidosis is greater in
      younger children.

PMID- 25612815
TI  - Weight-to-height ratio and aerobic capacity in 15-year-old male taekwondo martial
      artists.
AB  - INTRODUCTION: Martial arts are growing in popularity throughout the whole world.
      Their beneficial influence on physical development and fitness is noteworthy.
      Martial arts are an attractive form of physical recreation, constitute a perfect
      means for combating stress, and have a positive effect on general health,
      including during rehabilitation. AIM OF THE STUDY: The aim of this study is to
      assess physical development and aerobic capacity in boys who practice taekwondo
      and to determine the relationships between results of a fitness test and
      particular parameters of physical development. MATERIAL AND METHODS: Study
      participants comparised 51 boys aged 15 years who practiced taekwondo (with
      training experience ranging from 1 to 6 years). Volkov's modification of the
      Harvard Step Test was used to assess body height and body mass. BMI was also
      calculated. Centile charts were used to assess weight-to-height ratio and the
      level of measured parameters. BMI was analyzed according to the Cole
      classification system. Dispersion was calculated using a coefficient of
      variation. The Pearson product-moment correlation coefficient between selected
      parameters was also calculated. RESULTS: Most study participants had normal BMI,
      but 30% showed overweight and 13% showed underweight or emaciation. Weight-to
      height ratio differed significantly from the norm in 33% of the boys when
      compared to centile charts. All participants had average aerobic capacity.
      However, when weight-to-height ratio was compared to the results of the Harvard
      Step Test, boys with normal body proportions performed much better in the test
      than boys with abnormal body mass (p<0.05). CONCLUSIONS: Study participants
      showed abnormal weight-to-height ratio mainly in terms of overweight. The boys
      had greater body height and body mass compared to the general Polish population.
      Aerobic capacity differed considerably between participants.

PMID- 25612816
TI  - [Klinefelter syndrome in a boy with symptoms of precocious puberty].
AB  - Klinefelter syndrome is one of the most frequent sex chromosomal aberration. It
      is usually not recognized before puberty and many patients remain never
      diagnosed. Delayed puberty and hypergonadotropic hypogonadism are typical in this
      syndrome. Early diagnosis and therapy with androgens is important for patients.
      We present case of 8-year old boy with Klinefelter syndrome who was admitted to
      our department because of precocious puberty. 

PMID- 25612817
TI  - Cytoprotection against beta-amyloid (Abeta) peptide-mediated oxidative damage and
      autophagy by Keap1 RNAi in human glioma U87mg cells.
AB  - Extensive oxidative stress has been considered a primary pathological factor for
      many neurodegenerative disorders (NDDs). We speculated that the oxidative damage
      to brain cells can be managed by promoting the endogenous cellular antioxidants
      through the RNA interference (RNAi) against Keap1 (kelch-like ECH-associated
      protein). Keap1 acts as a negative regulator of Nrf2 (NF-E2-related factor 2)
      that represses the activation of the antioxidant responsive element (ARE). Here,
      we investigated whether Keap1 knockdown enhances the cellular antioxidant
      capacity and provides the neuroprotection against oxidative stress from hydrogen
      peroxide and beta-amyloid (Abeta) peptide in U87mg cells. We found that the Keap1
      siRNA pre-treated group displayed higher expression of diverse antioxidant genes
      and an increased antioxidant capacity compared to the control group. Moreover,
      the Keap1 RNAi exerted a cytoprotective effect against H2O2 treatment. In Abeta
      peptide treatment experiments, the Keap1 siRNA pre-treated groups maintained
      acceptable cell viability, relatively intact cellular morphology, and controlled
      oxidative damage levels while the control groups suffered from Abeta peptide
      mediated neurotoxicity. Keap1 RNAi also attenuated the oxidative stress-mediated
      autophagy as well. These findings suggest that Keap1 RNAi can serve as a
      therapeutic strategy for relieving oxidative stress-associated symptoms in many
      NDDs. 

PMID- 25612818
TI  - Biomolecular recognition ability of RecA proteins for DNA on single-walled carbon
      nanotubes.
AB  - We examined the biomolecular recognition ability of RecA proteins using single
      walled carbon nanotubes (SWNTs) wrapped with a single-stranded DNA (ssDNA)
      molecule as a mimic for the usual ssDNA molecules. The ssDNA-SWNT hybrids showed
      larger diameters compared to those of the usual ssDNA molecules. As a result,
      RecA molecules bound to the ssDNA-SWNTs, as observed using atomic force
      microscopy and agarose gel electrophoresis. On the other hand, when
      carboxymethylcellulose (CMC) was used rather than ssDNA, the RecA molecules did
      not bind to the CMC-SWNT hybrids. Our results indicate that RecA molecules
      recognize ssDNA on SWNT surfaces as DNA molecules through their biomolecular
      recognition ability. 

PMID- 25612819
TI  - Mannosylated and lipid A-incorporating cationic liposomes constituting
      microneedle arrays as an effective oral mucosal HBV vaccine applicable in the
      controlled temperature chain.
AB  - To develop an effective, convenient and stable mucosal vaccine against hepatitis
      B virus (HBV), the mannose-PEG-cholesterol/lipid A-liposomes (MLLs) loaded with
      HBsAg were prepared by the procedure of emulsification-lyophilization and,
      subsequently, filled into the microholes of microneedle array reverse molds and
      dried to form the proHBsAg-MLLs microneedle arrays (proHMAs). The proHMAs were
      stable even at 40  degrees C for up to 3 days and hard enough to pierce porcine
      skin but, upon rehydration, rapidly dissolved recovering the HBsAg-MLLs without
      obvious changes in size and antigen association efficiency. Notably, immunization
      of mice only once with the proHMAs at oral mucosa induced robust systemic and
      widespread mucosal immunoresponses, as evidenced by the high levels of HBsAg
      specific IgG in the sera and IgA in the salivary, intestinal and vaginal
      secretions. In addition, a strong cellular immunity against HBV had been
      established through a mixed Th1/Th2 response, as confirmed by a significant
      increase in CD8(+) T cells as well as the enhanced levels of IgG2a and IFN-gamma
      in the treated mice. Thus, the proHMAs can be conveniently vaccinated via oral
      mucosal route to set up a multiple immune defense against HBV invasion and, in
      addition, may be a stable HBV vaccine applicable in the controlled temperature
      chain for wide distribution.

PMID- 25612820
TI  - Monolithic polymer microlens arrays with high numerical aperture and high packing
      density.
AB  - This work reports a novel method for monolithic fabrication of high numerical
      aperture polymer microlens arrays (high-NA MLAs) with high packing density (PD)
      at wafer level. The close-packed high-NA MLAs were fabricated by incorporating
      conformal deposition of ultrathin fluorocarbon nanofilm and melting the
      cylindrical polymer islands. The NA and PD of hemispherical MLAs with a hexagonal
      arrangement increase up to 0.6 and 89%, respectively. The increase of NA enhances
      the lens transmission securing the beam width down to 1.1 MUm. The close-packed
      high-NA MLAs enable high photon collection efficiency with signal-to-noise ratio
      greater than 50:1. 

PMID- 25612821
TI  - Definitions (and Current Controversies) of Diabetes and Prediabetes.
AB  - Diagnosis of type 2 diabetes and prediabetes is mandatory. Chronic hyperglycemia
      in diabetes is associated with long-term micro- and macrovascular as well as with
      neurological complications. Prediabetes predisposes patients to develop diabetes
      and macrovascular disease. Diagnosis of diabetes is established on (at least) one
      of the following criteria: a fasting plasma glucose >= 126 mg/dl (7.0 mmol/l), a
      casual plasma glucose >= 200 mg/dl (11.1 mmol/l) in the presence of symptoms, a 2
      h plasma glucose during the 75-g oral glucose tolerance test (OGTT) >= 200 mg/dl
      (11.1 mmol/l) and/or an HbA1c >= 6.5%. Prediabetes is defined by the Position
      Statement of the American Diabetes Association as a fasting plasma glucose
      between 100 and 125 mg/dl (5.6 - 6.9 mmol/l) [a condition called Impaired Fasting
      Glucose] and/or by a 2-h plasma glucose during OGTT 140 - 199 mg/dl (7.8 - 11.0
      mmol) [Impaired Glucose Tolerance] and/or a HbA1c level 5.7 - 6.4%, with however
      some potential discordance between tests. The threshold of fasting plasma glucose
      defining Impaired Fasting Glucose as well as the adequacy of HbA1c as a correct
      diagnostic tool for prediabetes is still debated. 

PMID- 25612822
TI  - The Personalized Approach for Detecting Prediabetes and Diabetes.
AB  - A personalized approach for prediabetes and diabetes detection is presented, with
      its rationale and implications. Type 2 diabetes (T2DM) detection is particularly
      suitable to a personalized approach since the essence of its diagnosis is the
      identification of individuals who are at most risk of developing complications of
      the disease and who may benefit from intervention. Thresholds of glucose
      parameters for T2DM diagnosis have decreased over the years, as levels considered
      normal have been found to confer risks of complications. A continuum of glucose
      parameters, rather than universal thresholds, seems to better reflect the risks
      of diabetes and its complications. Individual trajectories of progression to
      diabetes suggest the possibility of establishing personalized profiles based on
      serial measurements. Demographic, clinical, genetic, and environmental factors
      need also be considered. Different diagnostic criteria are found to identify
      different phenotypes of T2DM. A personalized approach is needed to apply the
      accumulating knowledge to the recognition of individual risk for diabetes
      complications and effective interventions. 

PMID- 25612823
TI  - Novel application of mesenchymal stem cells from mammary artery.

PMID- 25612824
TI  - Persistent lipid abnormalities in statin-treated coronary artery disease patients
      with and without diabetes in China.
AB  - BACKGROUND: We evaluate the prevalence of persistent lipid abnormalities and
      statin use in Chinese coronary artery disease patients with and without diabetes.
      METHODS AND RESULTS: In this cross-sectional observational study, 8965
      outpatients from 200 clinical departments of 122 hospitals in 27 provinces
      nationwide of China who had coronary artery disease and were taking a statin were
      consecutively enrolled and divided into two groups based on diabetes status. The
      European Society of Cardiology/European Arthrosclerosis Society Guidelines for
      the management of dyslipidemias and the Chinese Guidelines on Prevention and
      Treatment of Dyslipidemia in Adults were used to compare the control rates of low
      density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL)
      cholesterol, and triglycerides (TG). Among the 8965 participants, 33.3% had been
      diagnosed with diabetes mellitus. According to the ESC Guidelines, the percentage
      of patients with not at goal LDL cholesterol did not differ significantly between
      patients with diabetes and those without diabetes (71.9% vs. 72.7%, P=0.46). The
      percentages of patients with not-at-goal levels of HDL and TG were 42.9% vs.
      34.4% (P<0.001) and 39.1% vs. 34.3% (P<0.001) among patients with diabetes and
      those without, respectively. Only approximately 10% of patients in both groups
      had optimal LDL-C, HDL-C, and TG levels. Compared with patients without diabetes,
      patients with diabetes were more likely to have mixed dyslipidemia. Atorvastatin
      (47.0%) and simvastatin (34.4%) were the two most frequently used statins, and
      the average statin dosage was 29.09mg/day (simvastatin equivalent). Less than 1%
      of patients were treated with another lipid-lowering drug in combination with a
      statin. CONCLUSIONS: Although international guidelines highly recommend intensive
      lipid modulation in patients with coronary artery disease, persistent
      dyslipidemia is still prevalent among these patients in China, even with statin
      treatment.

PMID- 25612825
TI  - Gold-nanoparticle-mediated jigsaw-puzzle-like assembly of supersized plasmonic
      DNA origami.
AB  - DNA origami has rapidly emerged as a powerful and programmable method to
      construct functional nanostructures. However, the size limitation of
      approximately 100 nm in classic DNA origami hampers its plasmonic applications.
      Herein, we report a jigsaw-puzzle-like assembly strategy mediated by gold
      nanoparticles (AuNPs) to break the size limitation of DNA origami. We
      demonstrated that oligonucleotide-functionalized AuNPs function as universal
      joint units for the one-pot assembly of parent DNA origami of triangular shape to
      form sub-microscale super-origami nanostructures. AuNPs anchored at predefined
      positions of the super-origami exhibited strong interparticle plasmonic coupling.
      This AuNP-mediated strategy offers new opportunities to drive macroscopic self
      assembly and to fabricate well-defined nanophotonic materials and devices. 

PMID- 25612826
TI  - The cryptococcal antigen lateral flow assay: A point-of-care diagnostic at an
      opportune time.
AB  - Cryptococcal meningitis is a devastating HIV-related opportunistic infection,
      affecting nearly 1 million individuals and causing over 500 000 deaths each year.
      The burden of disease is greatest in sub-Saharan Africa and Southeast Asia, where
      cryptococcal disease is the most common cause of meningitis. Rapid, accurate and
      affordable diagnosis of cryptococcal disease has been lacking in many of the most
      heavily affected areas. Here, we review a point-of-care assay for cryptococcal
      disease, the dipstick-formatted cryptococcal antigen lateral flow assay (LFA)
      (IMMY, Norman, OK). In comparison to culture, the assay is 99.5% sensitive and
      98% specific. In comparison to other commercially available tests for
      cryptococcal antigen, the LFA has equal or superior sensitivity and specificity
      in CSF, plasma and serum samples. We discuss potential applications for the use
      of the assay in resource-limited settings, including what is likely to be an
      important role of the LFA in screening for early cryptococcal infection before
      clinical disease and in evaluating pre-emptive treatment. 

PMID- 25612827
TI  - Effects of climate change on the persistence and dispersal of foodborne bacterial
      pathogens in the outdoor environment: A review.
AB  - According to the Intergovernmental Panel on Climate Change (IPCC), warming of the
      climate system is unequivocal. Over the coming century, warming trends such as
      increased duration and frequency of heat waves and hot extremes are expected in
      some areas, as well as increased intensity of some storm systems. Climate-induced
      trends will impact the persistence and dispersal of foodborne pathogens in myriad
      ways, especially for environmentally ubiquitous and/or zoonotic microorganisms.
      Animal hosts of foodborne pathogens are also expected to be impacted by climate
      change through the introduction of increased physiological stress and, in some
      cases, altered geographic ranges and seasonality. This review article examines
      the effects of climatic factors, such as temperature, rainfall, drought and wind,
      on the environmental dispersal and persistence of bacterial foodborne pathogens,
      namely, Bacillus cereus, Brucella, Campylobacter, Clostridium, Escherichia coli,
      Listeria monocytogenes, Salmonella, Staphylococcus aureus, Vibrio and Yersinia
      enterocolitica. These relationships are then used to predict how future climatic
      changes will impact the activity of these microorganisms in the outdoor
      environment and associated food safety issues. The development of predictive
      models that quantify these complex relationships will also be discussed, as well
      as the potential impacts of climate change on transmission of foodborne disease
      from animal hosts. 

PMID- 25612829
TI  - Body site Staphylococcus aureus colonization among maintenance hemodialysis
      patients.
AB  - BACKGROUND: Patients on maintenance hemodialysis therapy are at high risk for
      health care-associated infections. Staphylococcus aureus is a common cause of
      health care-associated infections among maintenance hemodialysis patients. It is
      established that S. aureus colonization is associated with an increased risk for
      subsequent infection in this population. There is an increasing number of reports
      that extranasal S. aureus colonization is more common than previously believed
      and in certain body sites even more common than nasal colonization. There are few
      data describing extranasal colonization among maintenance hemodialysis patients.
      METHODS: We surveyed 100 patients at 3 body sites (anterior nares, oropharynx,
      and inguinal region) for S. aureus colonization. Participants were also
      administered a standardized survey to assess risk factors for S. aureus
      colonization. RESULTS: We found that 42% (95% CI 32-52) of patients were S.
      aureus colonized in >1 body site. Extranasal colonization was found among 32%
      (95% CI 23-41). There were trends suggestive of an association between S. aureus
      colonization and younger age (OR 0.97, 95% CI 0.94-1.001, p = 0.06) and not
      having been hospitalized in the previous 12 months (OR 0.44, 95% CI 0.19-1.06, p
      = 0.14). CONCLUSION: Extranasal S. aureus colonization is common among
      maintenance hemodialysis patients with a prevalence of approximately one third.
      Future S. aureus decolonization efforts may need to consider not just nasal
      decolonization but also decolonization of the skin and oropharynx.

PMID- 25612828
TI  - Suppression of Mic60 compromises mitochondrial transcription and oxidative
      phosphorylation.
AB  - Precise regulation of mtDNA transcription and oxidative phosphorylation (OXPHOS)
      is crucial for human health. As a component of mitochondrial contact site and
      cristae organizing system (MICOS), Mic60 plays a central role in mitochondrial
      morphology. However, it remains unclear whether Mic60 affects mitochondrial
      transcription. Here, we report that Mic60 interacts with mitochondrial
      transcription factors TFAM and TFB2M. Furthermore, we found that Mic60 knockdown
      compromises mitochondrial transcription and OXPHOS activities. Importantly, Mic60
      deficiency decreased TFAM binding and mitochondrial RNA polymerase (POLRMT)
      recruitment to the mtDNA promoters. In addition, through mtDNA
      immunoprecipitation (mIP)-chromatin conformation capture (3C) assays, we found
      that Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D
      loop region. Taken together, our findings reveal a previously unrecognized
      important role of Mic60 in mtDNA transcription. 

PMID- 25612832
TI  - NOXIN as a cofactor of DNA polymerase-primase complex could promote
      hepatocellular carcinoma.
AB  - Oncogene activation or inactivation of tumor suppressor genes are crucial to
      tumor initiation and progression. DNA copy number amplification is one of many
      mechanisms that activate oncogenes in many tumors, including hepatocellular
      carcinoma (HCC). Although it has been known that some oncogenes such as c-myc
      amplification is involved in HCC pathogenesis, more oncogenes with DNA copy
      amplification contribute to HCC initiation and progression remain to be
      characterized. Here, we identified NOXIN as a novel potential oncogene with DNA
      copy number amplification by Single Nucleotide Polymorphism microarray-based
      genome-wide DNA copy number analysis of 43 human HCC samples. We identified the
      focal DNA gain and amplification region containing NOXIN on chromosome 11q14.1
      and NOXIN overexpression significantly associated with HCC progression. We then
      assessed the role of NOXIN in HCC cells. NOXIN overexpression promoted cellular
      proliferation, colony formation, cellular migration and in vivo tumorigenicity,
      whereas NOXIN knockdown attenuated these effects. Interestingly, NOXIN
      overexpression accelerated the G1-S phase transition by enhancing DNA synthesis.
      Furthermore, we found that NOXIN interacts with DNA polymerase alpha, suggesting
      that NOXIN may promote de novo DNA synthesis by promoting DNA polymerase-primase
      complex formation. These collective data indicated that NOXIN overexpression, as
      a result of genomic DNA gain or amplification, promotes HCC tumorigenesis by
      accelerating DNA synthesis and cell cycle progression, where NOXIN functions as a
      cofactor of DNA polymerase-primase complex by associating with DNA polymerase
      alpha. 

PMID- 25612833
TI  - Peripheral inflammation activated focal adhesion kinase signaling in spinal
      dorsal horn of mice.
AB  - Focal adhesion kinase (FAK) is one of the nonreceptor protein tyrosine kinases
      critical for the dynamic regulation of cell adhesion structures. Recent studies
      have demonstrated that FAK is also localized at excitatory glutamatergic synapses
      and is involved in long-term modification of synaptic strength. However, whether
      FAK is engaged in nociceptive processing in the spinal dorsal horn remains
      unresolved. The current study shows that intraplantar injection of complete
      Freund's adjuvant (CFA) in mice significantly increases FAK autophosphorylation
      at Tyr397, indicating a close correlation of FAK activation with inflammatory
      pain. FAK activation depended on the activity of N-methyl-D-aspartate-subtype
      glutamate receptor (NMDAR) and metabotropic glutamate receptor (mGluR) because
      pharmacological inhibition of NMDAR or group I mGluR totally abolished FAK
      phosphorylation induced by CFA. The active FAK operated to stimulate
      extracellular signal-regulated kinase1/2 (ERK1/2), which boosted the protein
      expression of GluN2B subunit-containing NMDAR at the synaptosomal membrane
      fraction. Inhibition of FAK activity by spinal expression of a kinase-dead
      FAK(Y397F) mutant repressed ERK1/2 hyperactivity and reduced the synaptic
      concentration of NMDAR in CFA-injected mice. Electrophysiological recording
      demonstrated that intracellular loading of specific anti-FAK antibody
      significantly reduced the amplitudes of NMDAR-mediated excitatory postsynaptic
      currents on lamina II neurons from inflamed mice but not from naive mice.
      Behavioral tests showed that spinal expression of FAK(Y397F) generated a long
      lasting alleviation of CFA-induced mechanical allodynia and thermal hyperalgesia.
      These data indicate that FAK might exaggerate NMDAR-mediated synaptic
      transmission in the spinal dorsal horn to sensitize nociceptive behaviors.

PMID- 25612834
TI  - Perceived Alienation of, and Social Support for, Siblings of Children With
      Cancer.
AB  - This descriptive study was performed to identify the relationships among
      alienation, general social support, and nurses' support for the siblings of
      children with cancer. The participants were 84 siblings of children with cancer.
      Alienation was measured by the revised version of Dean's Alienation Scale, and
      general social support was quantified by the revised version of Dubow and
      Ullman's Social Support Appraisal Scale. For nurses' support, Murray's Nurse
      Sibling Social Support Questionnaire was used. Data were collected from July 2011
      to December 2011. The participants' alienation was not particularly high (mean =
      42.24 +/- 12.72), but psychosocial vulnerability was identified from their
      answers to open-ended questions. The participants' perceived alienation showed a
      negative correlation with general social support, but no relationship with
      nurses' support. Although direct relationships between nurses' support and the
      siblings' alienation were not found in this study, the siblings perceived that
      the support of nurses was moderately helpful. Nurses can help siblings by
      providing support. 

PMID- 25612835
TI  - The Mediating Role of Resilience on Quality of Life and Cancer Symptom Distress
      in Adolescent Patients With Cancer.
AB  - Understanding how cancer symptom distress and resilience contribute to quality of
      life (QoL) in adolescent cancer and may potentially help these patients achieve
      better health-related outcomes. The objective of this study was to describe
      cancer symptom distress, QoL, and resilience in adolescents with cancer and to
      determine whether resilience is a mediating variable. Forty adolescent cancer
      patients were recruited, and data were collected via a demographic questionnaire,
      the Cancer Symptom Distress Scale, the Resilience Scale, and the Minneapolis
      Manchester Quality of Life Scale. Pearson's correlation, multiple regressions,
      and the Sobel test were conducted. Both resilience and cancer symptom distress
      were regressed against QoL, accounting for 62.1% of observed variation in QoL
      scores. The bootstrap result estimated the true indirect effect between -.0189
      and -.0024, with a 95% confidence interval. Resilience mediates the relationship
      between cancer symptom distress and QoL. Clinical use of a resilience measure,
      for example to use in developing and evaluating interventions focused on
      enhancing resilience, may be practical for nurses. 

PMID- 25612836
TI  - Harnessing technology to enhance delivery of clinical trials education for
      nurses: a report from the Children's Oncology Group.
AB  - The challenge of providing high-quality, relevant, time-sensitive continuing
      nursing education is particularly salient in pediatric oncology, where nurses
      commonly deliver complex protocol-based care to children enrolled on clinical
      trials. The Children's Oncology Group Nursing Discipline developed Portable
      Document Format multimedia modules to make a broad range of educational content
      regarding pediatric oncology clinical trials available to its membership. This
      time-sensitive educational content is accessible to nurses via asynchronous
      online education. To assess awareness of and user experience with the multimedia
      modules, a survey was conducted of nurses attending a Children's Oncology Group
      meeting. Over half (57%) of nurses were aware of the modules and half of those
      (51%) had viewed at least 1 module. Over 90% of nurses who viewed the modules
      were satisfied or very satisfied with the viewing experience; nurses younger than
      age 40 were 4 times more likely to be unaware of the modules than were older
      nurses (P = .007). 

PMID- 25612837
TI  - New biomarkers for early diagnosis of Lesch-Nyhan disease revealed by metabolic
      analysis on a large cohort of patients.
AB  - BACKGROUND: Lesch-Nyhan disease is a rare X-linked neurodevelopemental metabolic
      disorder caused by a wide variety of mutations in the HPRT1 gene leading to a
      deficiency of the purine recycling enzyme hypoxanthine-guanine
      phosphoribosyltransferase (HGprt). The residual HGprt activity correlates with
      the various phenotypes of Lesch-Nyhan (LN) patients and in particular with the
      different degree of neurobehavioral disturbances. The prevalence of this disease
      is considered to be underestimated due to large heterogeneity of its clinical
      symptoms and the difficulty of diagnosing of the less severe forms of the
      disease. We therefore searched for metabolic changes that would facilitate an
      early diagnosis and give potential clues on the disease pathogenesis and
      potential therapeutic approaches. METHODS: Lesch-Nyhan patients were diagnosed
      using HGprt enzymatic assay in red blood cells and identification of the causal
      HPRT1 gene mutations. These patients were subsequently classified into the three
      main phenotypic subgroups ranging from patients with only hyperuricemia to
      individuals presenting motor dysfunction, cognitive disability and self-injurious
      behavior. Metabolites from the three classes of patients were analyzed and
      quantified by High Performance Ionic Chromatography and biomarkers of HGprt
      deficiency were then validated by statistical analyses. RESULTS: A cohort of 139
      patients, from 112 families, diagnosed using HGprt enzymatic assay in red blood
      cells, was studied. 98 displayed LN full phenotype (86 families) and 41 (26
      families) had attenuated clinical phenotypes. Genotype/phenotype correlations
      show that LN full phenotype was correlated to genetic alterations resulting in
      null enzyme function, while variant phenotypes are often associated with missense
      mutations allowing some residual HGprt activity. Analysis of metabolites
      extracted from red blood cells from 56 LN patients revealed strong variations
      specific to HGprt deficiency for six metabolites (AICAR mono- and tri-phosphate,
      nicotinamide, nicotinic acid, ATP and Succinyl-AMP) as compared to controls
      including hyperuricemic patients without HGprt deficiency. CONCLUSIONS: A highly
      significant correlation between six metabolites and the HGprt deficiency was
      established, each of them providing an easily measurable marker of the disease.
      Their combination strongly increases the probability of an early and reliable
      diagnosis for HGprt deficiency.

PMID- 25612839
TI  - CORRIGENDUM: Resting-state functional reorganization of the rat limbic system
      following neuropathic injury.

PMID- 25612840
TI  - Iron intake and status of children aged 6-36 months in Europe: a systematic
      review.
AB  - BACKGROUND: Iron deficiency is the most common nutritional disorder in the world.
      Young children are particularly vulnerable to the consequences of iron deficiency
      because of their rapidly developing brain. This review evaluates the prevalence
      of inadequate iron intake and iron deficiency (anaemia) in European children aged
      6-36 months. SUMMARY: Computerized searches for relevant articles were performed
      in November 2013. A total of 7,297 citations were screened and 44 studies
      conducted in 19 European countries were included in this review. In both infants
      (6-12 months) and young children (12-36 months), the mean value of iron intakes
      in most countries was close to the RDA. Nevertheless, proportions of inadequate
      intakes were considerable, ranging from about 10% in the Netherlands up to 50% in
      Austria, Finland and the United Kingdom. The prevalence of iron deficiency varied
      between studies and was influenced by children's characteristics. Two to 25% of
      infants aged 6-12 months were found to be iron deficient, with a higher
      prevalence in those who were socially vulnerable and those who were drinking
      cow's milk as a main type of drink in their first year of life. In children aged
      12-36 months, prevalence rates of iron deficiency varied between 3 and 48%.
      Prevalence of iron deficiency anaemia in both age groups was high in Eastern
      Europe, as high as 50%, whereas the prevalence in Western Europe was generally
      below 5%. KEY MESSAGES: In most European countries, mean iron intakes of infants
      and children aged 6 to 36 months were found to be close to the RDA. Nevertheless,
      high proportions of inadequate intakes and high prevalence rates of iron
      deficiency were observed. Health programs should (keep) focus(ing) on iron
      malnutrition by educating parents on food choices for their children with iron
      rich and iron-fortified foods, and encourage iron supplementation programmes
      where iron intakes are the lowest.

PMID- 25612838
TI  - pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(D,L
      lactide) for tumor-targeting and controlled delivery of doxorubicin and P
      glycoprotein inhibitor.
AB  - The combination of a chemotherapeutic drug with a P-glycoprotein (P-gp) inhibitor
      has emerged as a promising strategy for treating multidrug resistance (MDR)
      cancer. To ensure that two drugs can be co-delivered to the tumor region and
      quickly released in tumor cells, tumor-targeted and pH-sensitive polymeric
      micelles were designed and prepared by combining cationic ring-opening
      polymerization of 2-ethyl-2-oxazoline (EOz) with anionic ring-opening
      polymerization of D,L-lactide (LA), and then encapsulating doxorubicin (DOX) and
      D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) into the
      micelles self-assembled by poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA)
      and DSPE-PEG-folate. PEOz-PLA exhibited a low critical micelle concentration and
      negligible cytotoxicity. The micelles enabled the rapid release of DOX when pH
      decreased from 7.4 to 5.0. The targeting ability of the micelles was demonstrated
      by in vitro flow cytometry in KBv cells and in vivo real time near-infrared
      fluorescence imaging in KBv tumor-bearing nude mice. The efficiency of MDR
      reversion for the micelles was testified by enhancement of intracellular DOX
      accumulation and cytotoxicity. The efficient drug delivery by the micelles was
      attributed to synergistic effects of folate-mediated targeting, pH-triggered drug
      release and TPGS1000-aroused P-gp inhibition. Therefore, the designed
      multifunctional polymeric micelles may have significant promise for therapeutic
      application of MDR cancer.

PMID- 25612842
TI  - Persistent pityriasis rosea: an unusual form of pityriasis rosea with persistent
      active HHV-6 and HHV-7 infection.
AB  - Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease,
      associated with the reactivation of the human herpesvirus 6 (HHV-6) and/or human
      herpesvirus 7 (HHV-7) that usually lasts 6-8 weeks. We studied, from a clinical
      and virological point of view, 12 patients in whom the features of PR lasted
      longer than 12 weeks, defining this form of the disease as persistent PR (PPR).
      As in typical PR, in most of the PPR patients the disease begins with a herald
      patch, but compared to typical PR, systemic symptoms and oral lesions are more
      common. Moreover, in PPR we found a persistent reactivation of HHV-6 and/or HHV-7
      with higher viral loads than in typical PR, accounting for the unusual
      persistence of the illness, the more frequent and severer systemic symptoms and
      the oral lesions. In conclusion, we describe an unusual persistent form of PR,
      whose prevalence has probably been underestimated so far and which should be
      added to the other variants of PR.

PMID- 25612841
TI  - Nox4 is a major source of superoxide production in human brain pericytes.
AB  - BACKGROUND: Pericytes are multifunctional cells surrounding capillaries and
      postcapillary venules. In brain microvasculature, pericytes play a pivotal role
      under physiological and pathological conditions by producing reactive oxygen
      species (ROS). The aims of this study were to elucidate the source of ROS and its
      regulation in human brain pericytes. METHODS: The expression of Nox enzymes in
      the cells was evaluated using RT-PCR and western blot. Superoxide production was
      determined by superoxide dismutase-inhibitable chemiluminescence. Silencing of
      Nox4 was performed using RNAi, and cell proliferation was evaluated using the 3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium (MTS) assay. RESULTS: Nox4 was predominant among the Nox family in
      human brain pericytes. Membrane fractions of cells produced superoxide in the
      presence of NAD(P)H. Superoxide production was almost abolished with
      diphenileneiodonium, a Nox inhibitor; however, inhibitors of other possible
      superoxide-producing enzymes had no effect on NAD(P)H-dependent superoxide
      production. Pericytes expressed angiotensin II (Ang II) receptors, and Ang II
      upregulated Nox4 expression. Hypoxic conditions also increased the Nox4
      expression. Silencing of Nox4 significantly reduced ROS production and attenuated
      cell proliferation. CONCLUSION: Our study showed that Nox4 is a major superoxide
      producing enzyme and that its expression is regulated by Ang II and hypoxic
      stress in human brain pericytes. In addition, Nox4 may promote cell growth.

PMID- 25612843
TI  - Trimetazidine pretreatment inhibits myocardial apoptosis and improves cardiac
      function in a Swine model of coronary microembolization.
AB  - OBJECTIVE: Trimetazidine (TMZ) is a well-known anti-ischemic agent; however, its
      efficacy and mechanism of cardioprotection on coronary microembolization (CME)
      are largely unknown. The present study was undertaken to determine whether TMZ
      pretreatment could attenuate myocardial apoptosis and improve cardiac function in
      a swine model of CME. METHODS: Fifteen swine were randomly and equally divided
      into a sham-operated (control) group, CME group and CME plus TMZ (TMZ) group. CME
      was induced by injecting inert plastic microspheres (42 MUm in diameter) into the
      left anterior descending artery. For the control group, the same dose of normal
      saline was substituted for the microspheres, and the TMZ group was pretreated
      with TMZ 30 min before microsphere injection. Cardiac function was assessed by
      echocardiography, myocardial apoptosis was detected by TUNEL staining, and the
      expression levels of cleaved caspase-9/3 were measured by Western blot 12 h after
      operation. RESULTS: Compared to the control group, cardiac function in the CME
      group was significantly decreased (p < 0.05); however, TMZ pretreatment showed
      significantly improved cardiac function as compared to the CME group (p < 0.05).
      The myocardial apoptotic rate and the expression levels of cleaved caspase-9/3
      increased remarkably in CME group as compared with the control group (p < 0.001).
      Again, TMZ pretreatment significantly reduced the apoptotic rate and also the
      expression levels of cleaved caspase-9/3 (p < 0.001). CONCLUSION: The present
      study demonstrated that TMZ pretreatment could significantly inhibit CME-induced
      myocardial apoptosis and improve cardiac function, and that the cardioprotective
      effect appeared to be mediated by the blockade of the mitochondrial apoptotic
      pathway. These results emphasize the importance of TMZ pretreatment in the
      therapy of CME-induced myocardial injury.

PMID- 25612844
TI  - The effect of the anabolic steroid, nandrolone, in conditioned place preference
      and D1 dopamine receptor expression in adolescent and adult mice.
AB  - Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking
      their anabolic effects, even though later on, many could develop
      neuropsychological dependence. Previously, we have shown that nandrolone induces
      conditioned place preference (CPP) in adult male mice. However, whether
      nandrolone induces CPP during adolescence remains unknown. In this study, the CPP
      test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in
      adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for
      reward-related processes, the effect of nandrolone on the expression of D1DR in
      the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to
      our previous results, nandrolone induced CPP in adults. However, in adolescents,
      nandrolone failed to produce place preference. At the molecular level, nandrolone
      decreased D1DR expression in the NAc only in adult mice. Our data suggest that
      nandrolone may not be rewarding in adolescents at least during short-term use.
      The lack of nandrolone rewarding effects in adolescents may be due, in part to
      differences in D1DR expression during development.

PMID- 25612846
TI  - MicroRNAs and the response to injury in atherosclerosis.
AB  - Endothelial cells (ECs) at arterial branching points are physiologically
      subjected to chronic damage by disturbed blood flow, which triggers a vascular
      wound healing response. Additional damage by hyperlipidaemia perturbs this
      delicate balance of endothelial injury and regeneration, and the progressive
      accumulation of noxious modified lipoproteins leads to macrophage death. Several
      miRNAs such as miR-92a and miR-712, which modulate EC proliferation and
      inflammation, are up-regulated by disturbed flow in ECs, and contribute to
      atherosclerosis. In addition, reduced endothelial levels of miR-126-5p limit the
      regenerative capacity of ECs, which becomes apparent by insufficient endothelial
      repair under hyperlipidemic stress. In macrophages, miR-342-5p induces the
      expression of miR-155 during the progression of atherosclerosis, which promotes
      inflammatory gene expression and inhibits efferocytosis by targeting Bcl6, thus
      contributing to necrotic core formation. Deciphering the complex cell- and
      context-specific effects of miRNAs during vascular wound healing appears
      essential for the development of miRNA-based therapies of atherosclerosis.

PMID- 25612845
TI  - Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer
      matrix fentanyl patch: single dose administration in healthy volunteers.
AB  - AIMS: Transdermal fentanyl is a well established treatment for cancer pain. The
      aim of the present study is to assess the relative bioavailability of fentanyl
      from two different transdermal systems by evaluating plasma drug concentrations
      after single administration of Fentalgon(r) (test), a novel bilayer matrix type
      patch, and Durogesic SMAT (reference), a monolayer matrix type patch. In the
      Fentalgon patch the upper 6% fentanyl reservoir layer maintains a stable
      concentration gradient between the lower 4% donor layer and the skin. The system
      provides a constant drug delivery over 72 h. METHODS: This was an open label,
      single centre, randomized, single dose, two period crossover clinical trial, that
      included 36 healthy male volunteers. The patches were applied to non-irritated
      and non-irradiated skin on the intraclavicular pectoral area. Blood samples were
      collected at different time points (from baseline to 120 h post-removal of the
      devices) and fentanyl concentrations were determined using a validated LC/MS/MS
      method. Bioequivalence was to be claimed if the 90% confidence interval of
      AUC(0,t) and C(max) ratios (test: reference) were within the acceptance range of
      80-125% and 75-133%, respectively. RESULTS: The 90% confidence intervals of the
      AUC(0,t) ratio (116.3% [109.6, 123.4%]) and C(max) ratio (114.4% [105.8, 123.8%]
      were well included in the acceptance range and the C(max) ratio also met the
      narrower bounds of 80-125%. There was no relevant difference in overall safety
      profiles of the two preparations investigated, which were adequately tolerated,
      as expected for opioid-naive subjects. CONCLUSIONS: The new bilayer matrix type
      patch, Fentalgon(r), is bioequivalent to the monolayer matrix type Durogesic SMAT
      fentanyl patch with respect to the rate and extent of exposure of fentanyl
      (Eudra/CT no. 2005-000046-36).

PMID- 25612847
TI  - Bortezomib in combination with infusional dose-adjusted EPOCH for the treatment
      of plasmablastic lymphoma.
AB  - Plasmablastic lymphoma (PBL) is a rare and aggressive CD20-negative lymphoma.
      Despite improvements of the biology behind PBL, it still represents a challenge
      from the diagnostic and therapeutic perspectives for pathologists and clinicians.
      PBL is characterized by high rates of relapse and short median survival with
      standard approaches. Here, we report the use of the combination of bortezomib and
      infusional etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin
      (V-EPOCH) in three patients with PBL; two were HIV-positive and one was HIV
      negative. All three patients obtained a durable complete response to V-EPOCH with
      survival times of 24, 18 and 12 months respectively. 

PMID- 25612848
TI  - DNA sequencing using polymerase substrate-binding kinetics.
AB  - Next-generation sequencing (NGS) has transformed genomic research by decreasing
      the cost of sequencing. However, whole-genome sequencing is still costly and
      complex for diagnostics purposes. In the clinical space, targeted sequencing has
      the advantage of allowing researchers to focus on specific genes of interest.
      Routine clinical use of targeted NGS mandates inexpensive instruments, fast
      turnaround time and an integrated and robust workflow. Here we demonstrate a
      version of the Sequencing by Synthesis (SBS) chemistry that potentially can
      become a preferred targeted sequencing method in the clinical space. This
      sequencing chemistry uses natural nucleotides and is based on real-time recording
      of the differential polymerase/DNA-binding kinetics in the presence of correct or
      mismatch nucleotides. This ensemble SBS chemistry has been implemented on an
      existing Illumina sequencing platform with integrated cluster amplification. We
      discuss the advantages of this sequencing chemistry for targeted sequencing as
      well as its limitations for other applications. 

PMID- 25612850
TI  - Excess wing in glass-forming glycerol and LiCl-glycerol mixtures detected by
      neutron scattering.
AB  - The relaxational dynamics in glass-forming glycerol and glycerol mixed with LiCl
      is investigated using different neutron scattering techniques. The performed
      neutron spin echo experiments, which extend up to relatively long relaxation time
      scales of the order of 10 ns, should allow for the detection of contributions
      from the so-called excess wing. This phenomenon, whose microscopic origin is
      controversially discussed, arises in a variety of glass formers and, until now,
      was almost exclusively investigated by dielectric spectroscopy and light
      scattering. Here we show that the relaxational process causing the excess wing
      can also be detected by neutron scattering, which directly couples to density
      fluctuations.

PMID- 25612849
TI  - Construct stability of an instrumented 2-level cervical corpectomy model
      following fatigue testing: biomechanical comparison of circumferential antero
      posterior instrumentation versus a novel anterior-only transpedicular screw-plate
      fixation technique.
AB  - INTRODUCTION: A high rate of complications in multilevel cervical surgery with
      corpectomies and anterior-only screw-and-plate stabilization is reported. A 360
      degrees -instrumentation improves construct stiffness and fusion rates, but adds
      the morbidity of a second approach. A novel ATS-technique (technique that used
      anterior transpedicular screw placement) was recently described, yet no study to
      date has analyzed its performance after fatigue loading. Accordingly, the authors
      performed an analysis of construct stiffness after fatigue testing of a cervical
      2-level corpectomy model reconstructed using a novel anterior transpedicular
      screw-and-plate technique (ATS-group) in comparison to standard antero-posterior
      instrumentation (360 degrees -group). MATERIALS AND METHODS: Twelve fresh-frozen
      human cervical spines were mounted on a spine motion tester to analyze
      restriction of ROM under loading (1.5 Nm) in flexion-extension (FE), axial
      rotation (AR), and lateral bending (LB). Testing was performed in the intact
      state, and after instrumentation of a 2-level corpectomy C4 + C5 using a cage and
      the constructs of ATS- and 360 degrees -group, after 1,000 cycles, and after
      2,000 cycles of fatigue testing. In the ATS-group (n = 6), instrumentation was
      achieved using a customized C3-C6 ATS-plate system. In the 360 degrees -group (n
      = 6), instrumentation consisted of a standard anterior screw-and-plate system
      with a posterior instrumentation using C3-C6 lateral mass screws. Motion data
      were assessed as degrees and further processed as normalized values after
      standardization to the intact ROM state. RESULTS: Specimen age and BMD were not
      significantly different between the ATS- and 360 degrees -groups. After
      instrumentation and 2,000 cycles of testing, no specimen exhibited a ROM greater
      than in the intact state. No specimen exhibited catastrophic construct failure
      after 2,000 cycles. Construct stiffness in the 360 degrees -group was
      significantly increased compared to the ATS-group for all loading conditions,
      except for FE-testing after instrumentation. After 2,000 cycles, restriction of
      ROM under loading in FE was 39.8 +/- 30% in the ATS-group vs. 2.8 +/- 2.3% in the
      360 degrees -group, in AR 60.4 +/- 25.8 vs 15 +/- 11%, and in LB 40 +/- 23.4 vs
      3.9 +/- 1.2%. Differences were significant (p < 0.05). CONCLUSION: 360 degrees 
      instrumentation resembles the biomechanical standard of reference for
      stabilization of 2-level corpectomies. An ATS-construct was also shown to confer
      high construct stiffness, significantly reducing the percentage ROM beyond that
      of an intact specimen after 2,000 cycles. This type of instrumentation might be a
      clinical valuable and biomechanically sound adjunct to multilevel anterior
      surgical procedures.

PMID- 25612851
TI  - Electromagnetic wave irradiation promotes osteoblastic cell proliferation and up
      regulates growth factors via activation of the ERK1/2 and p38 MAPK pathways.
AB  - BACKGROUND/AIMS: Periodontitis with bone resorption is caused by inflammatory
      reactions to bacterial infection. We recently reported that electromagnetic wave
      irradiation (EMWI) has bactericidal effects. However, the effects of EMWI on
      periodontal tissues remain unclear. This study was aimed to investigate the
      effects of EMWI on osteoblasts. METHODS: Osteoblastic cells MC3T3-E1 were treated
      with EMWI (500-1,000 kHz, 5 times, 1 sec/time). Cell growth and cytotoxicity were
      determined by cell proliferation assays and measurement of lactate dehydrogenase
      release, respectively. Gene expression and protein production of growth factors
      were analyzed using real-time PCR and ELISA, respectively. EMWI-activated
      cellular signal transduction pathways were investigated by immunoblotting and
      blocking assay with specific inhibitors. RESULTS: Osteoblasts proliferation was
      significantly enhanced 3 days after EMWI and no cytotoxicity was observed. EMWI
      up-regulated various growth factors, such as vascular endothelial growth factor
      (VEGF) and platelet-derived growth factor (PDGF). EMWI induced ERK1/2, p38 MAPK
      and SAPK/JNK phosphorylation within 5 min, and the production of PDGF-AlphaAlpha
      and VEGF was partially reduced by MAPK-specific inhibitor. CONCLUSION: These
      findings demonstrated that EMWI increases osteoblastic cell activity and the
      expression of growth factors via ERK1/2 and p38 MAPK pathways and suggested that
      EMWI may be beneficial to bone tissue repair such as periodontitis.

PMID- 25612852
TI  - Treatment of surgical site infections (SSI) IN patients with peripheral arterial
      disease: an observational study.
AB  - INTRODUCTION: The management of surgical site infections (SSI's) in vascular
      surgery has been challenging over the years. To assess the outcomes associated
      with the various strategies, we performed a review of all SSI's after elective
      vascular procedures in patients with moderate to severe peripheral arterial
      disease in a single centre hospital. METHODS: All patients with a SSI after
      peripheral vascular surgery were retrieved from a database on Surgical site
      infections (SSI)-surveillance after vascular surgery between March 2009 and
      January 2012. At admission, all patients were approached by microbiological wound
      sampling and empirical start of antibiotics. Further wound management was based
      on personal experience and preference of the attending vascular surgeon.
      Endpoints were treatment success (complete wound healing while staying alive and
      without major amputation), survival and major amputation during one year follow
      up. RESULTS: A total of 40 patients with a SSI were identified (60% superficial
      SSI and 40% deep SSI). In 92% of the patients with a superficial SSI's were
      successfully treated with adjusted antibiotics and incisional drainages. In the
      contrast, 25% of the patients with deep-SSI's were successfully treated. No
      particular treatment was more successful than the others. CONCLUSION: Adjusted
      antibiotic use and adequate wound drainage are sufficient strategies for
      superficial SSI management. The management of deep-SSI's is a challenging
      undertaking and future research on indications and timing of these wide arrays of
      treatment options is suggested.

PMID- 25612853
TI  - Bilateral internal mammary artery grafting: rationale and evidence.
AB  - Coronary artery bypass graft (CABG) surgery remains the preferred mode of
      revascularization in patients with complex multi-vessel coronary artery disease.
      The left internal mammary artery (IMA) and saphenous vein are the most commonly
      utilized conduits in CABG surgery and are still considered to be the gold
      standard by most surgeons. However, there is emerging evidence that use of
      bilateral IMAs is associated with significantly better long-term outcomes and the
      benefit increases with time from surgery. In spite of this incremental
      beneficiary effect, most surgeons are reluctant to use both IMAs, because it is
      technically more demanding, time-consuming and is associated with marginally
      higher sternal wound infection rates. This review highlights the histological
      features, physiological characteristics and genomics of IMAs that provide the
      basis for the use of these vessels during CABG surgery. Additionally, the
      superiority of the bilateral IMAs with regard to patency and long-term outcomes
      is also discussed in detail. Furthermore, the safety of using bilateral IMAs with
      regard to early postoperative outcomes with special reference to deep sternal
      wound infections has been addressed. The present review provides enough evidence
      to convince more surgeons about the advantages of bilateral IMA grafting. 

PMID- 25612854
TI  - Synthesis and fluorescence properties of new ester derivatives of isothiazolo
      [4,5-b] pyridine.
AB  - A two new compounds with potential biologically active were synthesized: ethyl 4
      (2H-4,6-dimethyl-3-oxo-2,3-dihydroisothiazolo [5,4-b] pyridin-2-yl) butanoate and
      ethyl 4-(2H-4,6-dimethyl-2,3-dihydroisothiazolo [5,4-b] pyridin-3-yloxy)
      butanoate. The structures of all of the newly formed compounds were identified by
      elemental analysis, FTIR and (1)H NMR. Their optical properties were studied in
      ethanol and n-hexane by UV-Vis absorption and fluorescence spectroscopy. The
      ground-state and excited-state properties were investigated using the density
      functional theory (DFT) and the time-dependent density functional theory (TDDFT)
      methods. The results showed differences between emission spectra in ethanol and n
      hexane solution (solvatochromism) for both new compounds. 

PMID- 25612855
TI  - Transcriptomic characterisation and genomic glimps into the toxigenic
      dinoflagellate Azadinium spinosum, with emphasis on polykeitde synthase genes.
AB  - BACKGROUND: Unicellular dinoflagellates are an important group of primary
      producers within the marine plankton community. Many of these species are capable
      of forming harmful algae blooms (HABs) and of producing potent phycotoxins,
      thereby causing deleterious impacts on their environment and posing a threat to
      human health. The recently discovered toxigenic dinoflagellate Azadinium spinosum
      is known to produce azaspiracid toxins. These toxins are most likely produced by
      polyketide synthases (PKS). Recently, PKS I-like transcripts have been identified
      in a number of dinoflagellate species. Despite the global distribution of A.
      spinosum, little is known about molecular features. In this study, we investigate
      the genomic and transcriptomic features of A. spinosum with a focus on polyketide
      synthesis and PKS evolution. RESULTS: We identify orphan and homologous genes by
      comparing the transcriptome data of A. spinosum with a diverse set of 18 other
      dinoflagellates, five further species out of the Rhizaria Alveolate Stramelopile
      (RAS)-group, and one representative from the Plantae. The number of orphan genes
      in the analysed dinoflagellate species averaged 27%. In contrast, within the A.
      spinosum transcriptome, we discovered 12,661 orphan transcripts (18%). The
      dinoflagellates toxins known as azaspiracids (AZAs) are structurally polyethers;
      we therefore analyse the transcriptome of A. spinosum with respect to polyketide
      synthases (PKSs), the primary biosynthetic enzymes in polyketide synthesis. We
      find all the genes thought to be potentially essential for polyketide toxin
      synthesis to be expressed in A. spinosum, whose PKS transcripts fall into the
      dinoflagellate sub-clade in PKS evolution. CONCLUSIONS: Overall, we demonstrate
      that the number of orphan genes in the A. spinosum genome is relatively small
      compared to other dinoflagellate species. In addition, all PKS domains needed to
      produce the azaspiracid carbon backbone are present in A. spinosum. Our study
      underscores the extraordinary evolution of such gene clusters and, in particular,
      supports the proposed structural and functional paradigm for PKS Type I genes in
      dinoflagellates.

PMID- 25612856
TI  - Percutaneous versus surgical management of lower extremity peripheral artery
      disease.
AB  - Lower extremity peripheral artery disease (PAD) is highly prevalent and can
      manifest as intermittent claudication or, in the most advanced form, critical
      limb ischemia. Revascularization, which can be accomplished by an endovascular or
      surgical approach, is performed to improve quality of life or, in severe cases,
      for limb salvage. Over the past decade, percutaneous catheter-based techniques
      have improved such that acute procedural success is high even in complex anatomy.
      Patency rates have also increased with the use of atherectomy devices and drug
      eluting stents. Often, patients with PAD have comorbidities that increase the
      risk of cardiovascular complications with surgical procedures. These factors have
      led to the adoption of an endovascular first strategy with surgical management
      reserved for selected patients. This review focuses on the most current clinical
      trials of endovascular therapy for PAD. In addition, older but relevant studies
      comparing endovascular and surgical approaches and contemporary surgical trials
      are presented for reference. 

PMID- 25612857
TI  - Familial hypercholesterolemia--epidemiology, diagnosis, and screening.
AB  - Familial hypercholesterolemia is among the commonest inherited metabolic
      disorders and is characterized by severely elevated LDL cholesterol levels.
      Mutations in four genes have been noted in patients with familial
      hypercholesterolemia (FH): LDL receptor (most common), apolipoprotein B (Apo B),
      proprotein convertase subtilin/kexin 9 (PCSK9), and low-density lipoprotein
      receptor adaptor protein (LDLRAP). In most cases, inheritance is autosomal co
      dominant with homozygotes having double the LDL cholesterol levels of
      heterozygotes. Autosomal recessive inheritance is rare. The prevalence of the
      heterozygous state has been estimated at 1 in 200 to 1 in 500 and of the
      homozygous state from 1 in 160,000 to 1 in 1,000, 000. Three formal diagnostic
      criteria have been proposed to diagnose FH in practice-MedPed, Simon Broome, and
      Dutch Lipid Clinic Network. The role of genetic testing and cascade screening
      among families is discussed in this review. 

PMID- 25612859
TI  - Preventive antibiotic therapy in stroke: PASSed away?

PMID- 25612860
TI  - Histologic analysis of clots in explanted axial continuous-flow left ventricular
      assist devices.

PMID- 25612861
TI  - Evidence for neoangiogenesis in the ischemic human heart after mechanical support
      and autologous bone marrow stem cell implantation.

PMID- 25612858
TI  - The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open
      label masked endpoint clinical trial.
AB  - BACKGROUND: In adults with acute stroke, infections occur commonly and are
      associated with an unfavourable functional outcome. In the Preventive Antibiotics
      in Stroke Study (PASS) we aimed to establish whether or not preventive
      antimicrobial therapy with a third-generation cephalosporin, ceftriaxone,
      improves functional outcome in patients with acute stroke. METHODS: In this
      multicentre, randomised, open-label trial with masked endpoint assessment,
      patients with acute stroke were randomly assigned to intravenous ceftriaxone at a
      dose of 2 g, given every 24 h intravenously for 4 days, in addition to stroke
      unit care, or standard stroke unit care without preventive antimicrobial therapy;
      assignments were made within 24 h after symptom onset. The primary endpoint was
      functional outcome at 3 months, defined according to the modified Rankin Scale
      and analysed by intention to treat. The primary analysis was by ordinal
      regression of the primary outcome. Secondary outcomes included death, infection
      rates, antimicrobial use, and length of hospital stay. Participants and
      caregivers were aware of treatment allocation but assessors of outcome were
      masked to group assignment. This trial is registered with controlled-trials.com,
      number ISRCTN66140176. FINDINGS: Between July 6, 2010, and March 23, 2014, a
      total of 2550 patients from 30 sites in the Netherlands, including academic and
      non-academic medical centres, were randomly assigned to the two treatment groups:
      1275 patients to ceftriaxone and 1275 patients to standard treatment (control
      group). 12 patients (seven in the ceftriaxone group and five in the control
      group) withdrew consent immediately after randomisation, leaving 2538 patients
      available for the intention-to-treat-analysis (1268 in the ceftriaxone group and
      1270 in the control group). 2514 (99%) of 2538 patients (1257 in each group)
      completed 3-month follow-up. Preventive ceftriaxone did not affect the
      distribution of functional outcome scores on the modified Rankin Scale at 3
      months (adjusted common odds ratio 0.95 [95% CI 0.82-1.09], p=0.46). Preventive
      ceftriaxone did not result in an increased occurrence of adverse events.
      Overgrowth infection with Clostridium difficile occurred in two patients (<1%) in
      the ceftriaxone group and none in the control group. INTERPRETATION: Preventive
      ceftriaxone does not improve functional outcome at 3 months in adults with acute
      stroke. The results of our trial do not support the use of preventive antibiotics
      in adults with acute stroke. FUNDING: Netherlands Organization for Health
      Research and Development, Netherlands Heart Foundation, and the European Research
      Council.

PMID- 25612862
TI  - Marital status and survival in left ventricular assist device patient
      populations.

PMID- 25612864
TI  - The metabolic syndrome and cardiovascular disease - an ongoing tsunami.
AB  - The metabolic syndrome represents a cluster of closely connected premorbid risk
      factors or diseases with visceral obesity type 2 diabetes, hypertension and low
      HLD/hypertriglyceridemia as established traits affecting about 20% in the adult
      European populations. This syndrome develops on a complex soil with
      overnutrition, low physical activity and psychosocial stress. Common
      comorbidities are fatty liver, sleep apnoe and endothelial dysfunction with
      cardiovascular complications, nephropathy and type 2 diabetes as "end-stage"
      diseases. Thus, a rational diagnostic is needed to elucidate the complex cluster
      of diseases as basis for an integrated therapy. There is a clear priority for
      life style intervention, however, most diseases of the metabolic syndrome need
      medical treatment. Medical treatment of single traits has to take into account
      possible pleiotropic or adverse effects on the other traits. This paper presents
      the pros and cons of major drug intervention for type 2 diabetes, hypertension,
      dyslipidemia and hypercoagulation in the context with the metabolic syndrome. 

PMID- 25612863
TI  - Severe hematologic complications after lung transplantation in patients with
      telomerase complex mutations.
AB  - BACKGROUND: Mutations in the telomerase complex (TERT and TR) are associated with
      pulmonary fibrosis and frequent hematologic manifestations. The aim of this study
      was to characterize the prognosis of lung transplantation in patients with TERT
      or TR mutations. METHODS: Patients with documented TERT or TR mutations who
      received a lung transplant between 2007 and 2013 in France were identified via an
      exhaustive search of the lung transplantation network, one expert genetic
      laboratory, and the clinical research network on rare pulmonary diseases.
      RESULTS: There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations
      who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary
      fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years
      (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was
      present in 7 patients before lung transplantation. After lung transplantation, 6
      patients developed myelodysplasia and/or bone marrow failure, directly
      contributing to death in 4 cases. Anemia was observed in 9 patients, and
      neutropenia was observed in 3 patients. The median survival after lung
      transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS: Patients with
      mutations of the telomerase complex are at high risk of severe hematologic
      complications after lung transplantation, in particular, bone marrow failure.
      Specific recommendations should be developed for appropriate guidance regarding
      hematologic risk assessment before transplantation and management of the post
      transplantation immunosuppressive regimen.

PMID- 25612865
TI  - [Betatrophin - the turn in diabetes treatment].
AB  - The topic of the present work is the appearance of the newest research in
      diabetes treatment. Till now, the patients were forced to inject insulin or take
      oral medicines to maintain proper glucose level. Introduction of the incretin
      group of medicines to the market turned out to be a breakthrough in diabetes
      treatment. It defers the necessity of insulin therapy in type 2 diabetes. Studies
      connected with amyline were the next step in diabetes therapy. The new research
      connected with peptide betatrophin seems to comes as the biggest surprise and
      hope for diabetics. The hormone stimulates B-cells proliferation, which leads to
      increase in endogenous insulin production. It generates a chance for a fewer
      number of injections, which will result in better quality of life. 

PMID- 25612866
TI  - [Vasopressin and jet lag disordes].
AB  - Circadian rhythm plays an important role in human physiology. Its abnormal
      functioning results, among others, in jet lag disorder (JLD- Jet Lag Disorder),
      which is a discomfort experienced by people travelling between time zones, as
      well as being the cause for metabolic diseases in people working shifts. Recent
      studies have shown the role of vasopressin V1a and V1b suprachiasmatic nucleus
      (SCN- surachiasmatic nucleus) of the hypothalamus in the regulation of circadian
      rhythms. Mice genetically lacking receptors are resistant to disturbances of
      circadian rhythm, and are characterized by an almost immediate adjustment to the
      new rhythm. A similar effect is achieved by pharmacologically blocking V1a and
      V1b receptors. Research gives hope of overcoming this disorder to travellers who
      traverse time zones at high speed, as well as creating the possibility of
      adaptation to shift work without provoking any negative consequences over one's
      health. 

PMID- 25612867
TI  - Psychomotor retardation in a girl with complete growth hormone deficiency.
AB  - Infants with complete growth hormone deficiency may suffer from psychomotor
      retardation in addition to severe growth failure. Without replacement therapy,
      they may have a compromised intellectual potential manifesting as learning
      disabilities and attention-deficit disorders in later life. In this
      communication, we discuss an infant who showed improvement in physical growth
      after growth hormone therapy but her psychomotor skills did not improve probably
      due to late start of treatment. There is a need to start growth hormone therapy
      as early as possible in infants with complete growth hormone deficiency to avoid
      adverse effects on psychomotor and brain development. 

PMID- 25612868
TI  - Panhypopituitarism after multisystem trauma.
AB  - INTRODUCTION: The pituitary gland plays a key role in hormonal regulation in the
      organism, contributing to maintenance of balance of basic vital functions. THE
      AIM OF THE STUDY: To emphasise the need for assessment of pituitary function
      after head injury, as correct diagnosis and hormone replacement therapy prove to
      be a life-saving therapy accelerating the recovery process. CASE REPORT: A
      healthy, normally developing 9-year-old girl, a child of young and healthy
      parents, was struck by a falling tree. The results of severe head trauma included
      adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of
      damage to the anterior and posterior pituitary gland. Administration of hormone
      replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly
      improved the patient's condition and facilitated effective rehabilitation.
      CONCLUSION: Determination of pituitary hormones in children after severe head
      injury should be an important part of diagnosis allowing identification of an
      early stage of acute hypopituitarism and acceleration of recovery through hormone
      replacement therapy.

PMID- 25612869
TI  - [Bloody nipple discharge in an 3,5-month-old boy].
AB  - Bloody nipple discharge in an infant is a distressing finding both for parents
      and the pediatrician who consults the baby. In adults the bleeding can be
      associated with breast carcinoma, especially when it is unilateral. In infants
      breast carcinoma are extremely rare. Usually, the bleeding is a benign process,
      but that does not mean that the children with this symptom should not be
      diagnosed and controlled. This paper reports a 3,5-month-old boy with bilateral
      bloody nipple discharge. Additionally, it presents previously described cases of
      bleeding from the nipples in children and proposed diagnostic approach. 

PMID- 25612871
TI  - 2D-DIGE screening of high-productive CHO cells under glucose limitation--basic
      changes in the proteome equipment and hints for epigenetic effects.
AB  - CHO derivates (Chinese hamster ovary) belong to the most important mammalian
      cells for industrial recombinant protein production. Many efforts have been made
      to improve productivity and stability of CHO cells in bioreactor processes. Here,
      we followed up one barely understood phenomenon observed with process
      optimizations: a significantly increased cell-specific productivity in late
      phases of glucose-limited perfusion cultivations, when glucose (and lactate)
      reserves are exhausted. Our aim was to elucidate the cellular activities
      connected to the metabolic shift from glucose surplus to glucose limitation
      phase. With 2D-DIGE, we compared three stages in a perfusion culture of CHO
      cells: the initial growth with high glucose concentration and low lactate
      production, the second phase with glucose going to limitation and high lactate
      level, and finally the state of glucose limitation and also low lactate
      concentration but increased cell-specific productivity. With our proteomic
      approach we were able to demonstrate consequences of glucose limitation for the
      protein expression machinery which also could play a role for a higher
      recombinant protein production. Most interestingly, we detected epigenetic
      effects on the level of proteins involved in histone modification (HDAC1/-2, SET,
      RBBP7, DDX5). Together with shifts in the protein inventory of energy metabolism,
      cytoskeleton and protein expression, a picture emerges of basic changes in the
      cellular equipment under long-term glucose limitation of CHO cells. 

PMID- 25612870
TI  - Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular
      Mechanisms Driven by 17beta-Estradiol.
AB  - Kisspeptin is a neuropeptide that signals via a Galphaq-coupled receptor, GPR54,
      in gonadotropin-releasing hormone (GnRH) neurons and is essential for pubertal
      maturation and fertility. Kisspeptin depolarizes and excites GnRH neurons
      primarily through the activation of canonical transient receptor potential (TRPC)
      channels and the inhibition of K+ channels. The gonadal steroid 17beta-estradiol
      (E2) upregulates not only kisspeptin (Kiss1) mRNA but also increases the
      excitability of the rostral forebrain Kiss1 neurons. In addition, a primary
      postsynaptic action of E2 on GnRH neurons is to upregulate the expression of
      channel transcripts that orchestrate the downstream signaling of kisspeptin in
      GnRH neurons. These include not only TRPC4 channels but also low-voltage
      activated T-type calcium channels and high-voltage-activated L-, N- and R-type
      calcium channel transcripts. Moreover, E2 has direct membrane-initiated actions
      to alter the excitability of GnRH neurons by enhancing ATP-sensitive potassium
      channel activity, which is critical for maintaining GnRH neurons in a
      hyperpolarized state for the recruitment of T-type calcium channels that are
      important for burst firing. Therefore, E2 modulates the excitability of GnRH
      neurons as well as of Kiss1 neurons by altering the expression and/or function of
      ion channels; moreover, kisspeptin provides critical excitatory input to GnRH
      neurons to facilitate burst firing activity and peptide release. 

PMID- 25612872
TI  - Regulation of astaxanthin and its intermediates through cloning and genetic
      transformation of beta-carotene ketolase in Haematococcus pluvialis.
AB  - Astaxanthin, a high-value ketocarotenoid used in the pharmaceutical and
      nutraceutical industries is mainly produced from green alga, Haematococcus
      pluvialis. It is biosynthesized by the action of key enzyme, beta-carotene
      ketolase (BKT) on beta-carotene through intermediates echinenone and
      canthaxanthin. In this study, the beta-carotene ketolase (bkt) gene was isolated
      from H. pluvialis and cloned in a vector pRT100 and further mobilized to a binary
      vector pCAMBIA 1304. The T-DNA of pCAMBIA 1304, which consists of cloned bkt, was
      successfully transformed to H. pluvialis through Agrobacterium mediation. The
      cloning and transformation of bkt in H. pluvialis was confirmed by Southern
      blotting and also by PCR analysis. Total carotenoids and astaxanthin content in
      the transformed cells were found to be 2-3-fold higher, while the intermediates
      like echinenone and canthaxanthin were found to be 8-10-fold higher than in the
      control cells. The expression level of carotenogenic genes like phytoene synthase
      (psy), phytoene desaturase (pds), lycopene cyclase (lcy), bkt, and beta-carotene
      hydroxylase (bkh) were found to be higher in transformed cells compared to the
      non-transformed (NT) H. pluvialis. 

PMID- 25612873
TI  - Construction of two Listeria ivanovii attenuated strains expressing Mycobacterium
      tuberculosis antigens for TB vaccine purposes.
AB  - Bacillus Calmette-Guerin (BCG) has failed in complete control of tuberculosis
      (TB), thus, novel tuberculosis vaccines are urgently needed. We have constructed
      several TB vaccine candidates, which are characterized by the use of Listeria
      ivanovii (LI) strain as an antigen delivery vector. Two L. ivanovii attenuated
      recombinant strains L. ivanovii?actAplcB-Rv0129c and L. ivanovii?actAplcB-Rv3875
      were successfully screened. Results from genome PCR and sequencing showed that
      the Mycobacterium tuberculosis antigen gene cassette coding for Ag85C or ESAT-6
      protein respectively had been integrated into LI genome downstream of mpl gene.
      Western blot confirmed the secretion of Ag85C or ESAT-6 protein from the
      recombinant LI strains. These two recombinant strains showed similar growth
      curves as wide type strain in vitro. In vivo, they transiently propagated in mice
      spleen and liver, and induced specific CD8(+) IFN-gamma secretion. Therefore, in
      this paper, two novel LI attenuated strains expressing specific TB antigens were
      successfully constructed. The promising growth characteristics in mice immune
      system and the capability of induction of IFN-gamma secretion make them of
      potential interest for development of TB vaccines. 

PMID- 25612874
TI  - [Dehydration and malnutrition as two independent risk factors of death in a
      Senegalese pediatric hospital].
AB  - Inpatient mortality is an indicator of the quality of care. We analyzed the
      mortality of under 5-year-old hospitalized children in the pediatric ward of
      Aristide Le Dantec Hospital for updating our data 10 years after our first study.
      METHODS: We analyzed the data of the children hospitalized between 1 January and
      31 December 2012. For each child, we collected anthropometric measurements
      converted to a z-score related to World Health Organization growth data. Logistic
      regression-generating models built separately with different anthropometric
      parameters were used to assess the risk of mortality according to children's
      characteristics. RESULTS: Data from 393 children were included. The overall
      mortality rate was 10% (39/393). Using logistic regression, the risk factors
      associated with death were severe wasting (odds ratio [OR]=8.27; 95% confidence
      interval [95% CI]) [3.79-18], male gender (OR=2.98; 95% CI [1.25-7.1]),
      dehydration (OR=5.4; 95% CI [2.54-13.43]) in the model using the weight-for
      height z-score; male gender (OR=2.5; 95% CI [1.11-5.63]), dehydration (OR=8.43;
      95% CI [3.83-18.5]) in the model using the height-for-age z-score; male gender
      (OR=2.7; 95% CI [1.19-6.24]), dehydration (OR=7.5; 95% CI [3.39-16.76]), severe
      deficit in the weight-for-age z-score (OR=2.4; 95% CI [1.11-5.63]) in the model
      using the weight-for-age z-score; and male gender (OR=2.5; 95% CI [1.11-5.63])
      and dehydration (OR=8.43; 94% CI [3.83-18.5]) in the last model with mid-upper
      arm circumference (MUAC). Dehydration and malnutrition were two independent risk
      factors of death. The protocols addressing dehydration and malnutrition
      management should be audited and performed systematically for each child's
      anthropometric measurements at admission.

PMID- 25612875
TI  - Association of N-acetylcysteine and glucagon during percutaneous cholangiography
      in the treatment of inspissated bile syndrome.
AB  - Inspissated bile syndrome (IBS) is a rare neonatal disease. In the majority of
      cases, it resolves spontaneously and treatment is conservative. Follow-up is
      recommended with close monitoring of laboratory tests. When IBS does not resolve
      spontaneously, a catheter can be inserted into the gallbladder for
      cholangiography, which allows irrigation and drainage. Despite this treatment,
      some biliary tract obstruction may persist. We report on the case of a 3-month
      old infant whose continuous biliary obstruction caused by IBS was successfully
      managed by interventional radiology with the association of N-acetylcysteine and
      glucagon. Even as first-line agents, these would allow more rapid clearance of
      gallstones and prevent infectious complications of indwelling catheters as well
      as decrease the need for surgery. 

PMID- 25612876
TI  - [A short track to relieve pediatric emergency department overload].
AB  - INTRODUCTION: The number of emergency pediatric consultations continues to rise
      in France. The pediatric emergency department (PED) introduced relocated
      consultations (RlCs) for unwarranted visits to relieve the overload of emergency
      medical consultations. The objective of this study was to assess the advantages
      of implementing these RlCs. METHODS: A single-center prospective study was
      undertaken from 21st January to 18 March 2012, with RlCs opened on weekends from
      1 to 8 pm in the PED of the Nice Lenval University Hospital Center. All children
      referred for medical reasons during this period were included. One out of two
      children labeled stage 5 were transferred to the RlCs. The data evaluated were
      waiting time, duration of the medical consultation, transit time, and patient and
      medical staff satisfaction. RESULTS: Eight hundred and seventy-five patients were
      included. All patients in stages 1-2, 3, 4, and 5, relocated or not, had a mean
      waiting time before the medical consultation lasting 39.1, 57.7, 54.8, 70.5, and
      52.7 min, respectively. The mean duration of the medical consultation was longer
      for stages 1-2 (61.6 min). The total time spent in the PED did not differ between
      stage 5 patients who were not relocated (121.3 min) and stages 1-2 (118 min), but
      both were longer than stage 5 patients who were relocated (90.3 min). Patients
      and medical staff expressed overall satisfaction during this period. DISCUSSION:
      By relocating one out of two stage 5 children, waiting times and consultation
      times decreased for all patients consulting at the PED. These results confirm
      that implementing RlCs has improved working conditions and quality of patient
      management.

PMID- 25612877
TI  - Releasable Conjugation of Polymers to Proteins.
AB  - Many synthetic strategies are available for preparing well-defined conjugates of
      peptides/proteins and polymers. Most reports on this topic involve coupling
      methoxy poly(ethylene glycol) to therapeutic proteins, a process referred to as
      PEGylation, to increase their circulation lifetime and reduce their
      immunogenicity. Unfortunately, the major dissuading dogma of PEGylation is that,
      in many cases, polymer modification leads to significant (or total) loss of
      activity/function. One approach that is gaining momentum to address this
      challenge is to release the native protein from the polymer with time in the body
      (releasable PEGylation). This contribution will present the state-of-the-art of
      this rapidly evolving field, with emphasis on the chemistry behind the release of
      the peptide/protein and the means for altering the rate of release in biological
      fluids. Linkers discussed include those based on the following: substituted
      maleic anhydride and succinates, disulfides, 1,6-benzyl-elimination, host-guest
      interactions, bicin, beta-elimination, biodegradable polymers, E1cb elimination,
      beta-alanine, photoimmolation, coordination chemistry, zymogen activation,
      proteolysis, and thioesters. 

PMID- 25612878
TI  - Neurovascular compromise due to true brachial artery aneurysm at the site of a
      previously ligated arteriovenous fistula: Case report and review of literature.
AB  - True arterial aneurysms of the upper extremity are rare. The case described is
      that of a 48-year-old man presenting with median neuropathy and distal vascular
      compromise 4 years after ligation of a brachiocephalic arteriovenous fistula. We
      describe our approach and present a review of the relevant literature. 

PMID- 25612879
TI  - The combined effects of alcohol and cannabis on driving: Impact on crash risk.
AB  - BACKGROUND/OBJECTIVES: Driving under the influence of alcohol or cannabis alone
      is associated with increased crash risk. This study explores the combined
      influence of low levels of alcohol (BAC<=0.08) and cannabis on crash risk.
      MATERIALS AND METHODS: Drivers aged 20 years or older who had been tested for
      both drugs and alcohol after involvement in a fatal crash in the United States
      (1991-2008) were examined using a case-control design. Cases were drivers with at
      least one potentially unsafe driving action (UDA) recorded in relation to the
      crash (e.g., weaving); controls had none recorded. We examined the prevalence of
      driving under the influence of alcohol, cannabis, and both agents, for drivers
      involved in a fatal crash. Adjusted odds ratios of committing an UDA for alcohol
      alone, THC alone, and their combined effect were computed via logistic regression
      and adjusted for a number of potential confounders. RESULTS: Over the past two
      decades, the prevalence of THC and alcohol in car drivers involved in a fatal
      crash has increased approximately five-fold from below 2% in 1991 to above 10% in
      2008. Each 0.01 BAC unit increased the odds of an UDA by approximately 9-11%.
      Drivers who were positive for THC alone had 16% increased odds of an UDA. When
      alcohol and THC were combined the odds of an UDA increased by approximately 8-10%
      for each 0.01 BAC unit increase over alcohol or THC alone. CONCLUSION: Drivers
      positive for both agents had greater odds of making an error than drivers
      positive for either alcohol or cannabis only. Further research is needed to
      better examine the interaction between cannabis concentration levels, alcohol,
      and driving. This research would support enforcement agencies and public health
      educators by highlighting the combined effect of cannabis at low BAC levels.

PMID- 25612880
TI  - Surveys of vehicle colour frequency and the transfer of vehicle paints to
      stationary objects in Sydney, Australia.
AB  - The interpretation of vehicle paint traces in forensic casework hinges on a
      number of factors including the type of paint, colour, number of layers, and
      background information. Vehicle colour surveys are an important source of
      information for the forensic paint examiner when interpreting the level of
      significance of a paint transfer between vehicles involved in a collision, or
      smears of vehicle paint left at a scene. The two surveys that are presented here
      investigated (i) the frequency of the colour of vehicles observed on both a
      motorway and suburban roads in Western Sydney and (ii) the frequency of different
      vehicle paint colours transferred to car park pillars and walls from five
      different car parks within North West Sydney, Australia. In the first survey, the
      highest frequency of vehicle colours recorded was white, grey, black and blue.
      The second survey resulted in very similar findings with the four most commonly
      seen colours across the five car parks being blue, white, red, and silver. The
      results in the second survey take into account the potential for anomalies within
      the data due to the use of painted service vehicles used within the car parks,
      such as trolleys and trailers. The results from both surveys were very similar to
      previous vehicle colour surveys that have been conducted and also corresponded to
      the vehicle colour registration data obtained from the NSW Roads and Maritime
      Service website. The results from these two surveys provide up to date statistics
      that can assist the forensic paint examiner with valuable background data when
      assessing the significance of vehicle paint evidence in casework. 

PMID- 25612881
TI  - Local mitochondrial DNA haplotype databases needed for domestic dog populations
      that have experienced founder effect.
AB  - Biological material from pets is often collected as evidence from crime scenes.
      Due to sample type and quality, mitochondrial DNA (mtDNA) is frequently evaluated
      to identify the potential contributor. MtDNA has a lower discriminatory power
      than nuclear DNA with multiple individuals in a population potentially carrying
      the same mtDNA sequence, or haplotype. The frequency distribution of mtDNA
      haplotypes in a population must be known in order to determine the evidentiary
      value of a match between crime scene evidence and the potential contributor of
      the biological material. This is especially important in geographic areas that
      include remote and/or isolated populations where founder effect may have lead to
      a decrease in genetic diversity and a non-random distribution of haplotypes
      relative to the population at large. Here we compared the haplotype diversity in
      dogs from the noncontiguous states of Alaska and Hawaii relative to the
      contiguous United States (US). We report a greater proportion of dogs carrying an
      A haplotype in Alaska relative to any other US population. Significant variation
      in the distribution of haplotype frequencies was discovered when comparing the
      haplotype diversity of dogs in Hawaii to that of the continental US. Each of
      these regions exhibits reduced genetic diversity relative to the contiguous US,
      likely due to founder effect. We recommend that specific databases be created to
      accurately represent the mitochondrial haplotype diversity in these remote areas.
      Furthermore, our work demonstrates the importance of local surveys for
      populations that may have experienced found effect. 

PMID- 25612882
TI  - Effect of flaxseed on blood lipid level in hyperlipidemic patients.
AB  - INTRODUCTION: Hyperlipidemia is one of the most important risk factors of
      ischemic heart disease. Previous studies showed that flaxseed has the potential
      to improve lipid profiles. In this study we investigated the effects of flaxseed
      powder intake on lipid profiles of patients with hyperlipidemia. MATERIALS AND
      METHODS: This study was a randomized controlled clinical trial. Seventy patients
      with hyperlipidemia participated in the research. After detailed diet and
      lifestyle education, blood samples were collected from the participants. Patients
      with hyperlipidemia were randomly divided in to two intervention and control
      groups. The intervention group received 30 g of raw flaxseed powder every day for
      40 days. Serum lipids were measured again in two groups after that time. Activity
      and food intakes of two groups were recorded. RESULTS: In the intervention group,
      weight and body mass index were considerably reduced. Total cholesterol was
      reduced in the intervention group and increased in the control group, both of
      which were significant. Low density lipoprotein significantly increased in the
      control group and reduced in intervention group; also, triglyceride was increased
      in the control group and reduced in the intervention group, which were
      significant Table 1. CONCLUSION: Based on the findings obtained in this research,
      flaxseed powder intake desirably reduced serum lipids. The differences between
      two groups on the basis of analysis of covariance test were significant. In all
      cases except for the HDL-c, this is an effective intervention. Therefore,
      flaxseed may be regarded as a useful therapeutic food for reducing
      hyperlipidemia.

PMID- 25612884
TI  - Physician responses to rising local unemployment rates: Healthcare provision to
      Medicare and privately insured patients.
AB  - Prior studies suggest that hospital care is countercyclical among Medicare
      beneficiaries, and if anything, procyclical among the non-elderly. In this paper,
      we provide the first physician-level analysis of changes in healthcare provision
      to Medicare and privately insured patients across the business cycle. Using
      Florida discharge data aggregated to the physician level, we find that as county
      unemployment rates increase, physicians treat fewer privately insured patients in
      both inpatient and outpatient settings. In contrast, physicians who are more
      exposed to income losses during recessions provide more care to Medicare patients
      as the unemployment rate rises. Further analysis suggests that easing capacity
      constraints may contribute to this rise in Medicare volume; however, even in
      areas that are not capacity constrained, care provided to Medicare patients
      remains countercyclical among physicians with a large share of privately insured
      patients. This pattern is consistent with demand inducement in response to a
      negative income shock. 

PMID- 25612883
TI  - Syndrome of inappropriate anti-diuretic hormone secondary to non-cirrhotic
      primary hepatocellular carcinoma.
AB  - BACKGROUND: The syndrome of inappropriate antidiuretic hormone secretion (SIADH)
      is usually seen in pulmonary malignancies, central nervous system disorders, and
      secondary to medications. SIADH has very rarely been encountered in primary
      hepatocellular carcinoma. Two cases were reported in Japan and 1 case in Spain
      after extensive investigation of the medical records. CASE REPORT: We report a
      case of a 71-year-old man who presented with confusion, cachexia, and abdominal
      symptoms in the form of vomiting and abdominal discomfort. On the initial work
      up, SIADH diagnosis was made. After an extensive work-up, the reason for SIADH
      turned out to be a newly diagnosed hepatocellular carcinoma. The precipitating
      factor for the cancer was not identified by history or by work-up. No metastasis
      was identified. Liver functions were preserved but patient was severely
      malnourished. CONCLUSIONS: SIADH can occur as a para-malignant feature of the
      malignancy. In our case, it was related to the hepatocellular carcinoma, which is
      a malignancy very rare to cause SIADH.

PMID- 25612885
TI  - Palladium(0)-catalyzed iminohalogenation of alkenes: synthesis of 2-halomethyl
      dihydropyrroles and mechanistic insights into the alkyl halide bond formation.
AB  - Although the advances on carbon halide reductive elimination have been made, the
      alkyl bromide and chloride analogues remain a challenge. Here, a palladium(0)
      catalyzed iminohalogenation of gamma,delta-unsaturated oxime esters is described,
      and the use of electron-poor phosphine ligands proved to be crucial to promoting
      alkyl bromide and chloride reductive elimination. Furthermore, S(N)2-type alkyl
      bromide and chloride reductive elimination has also been established.

PMID- 25612887
TI  - Quote ... unquote.

PMID- 25612888
TI  - Roles of 3,3',4',5-tetrachlorosalicylanilide in regulating extracellular electron
      transfer of Shewanella oneidensis MR-1.
AB  - Microbial extracellular electron transfer (EET) is critically involved in many
      pollutant conversion processes in both natural environment and engineered
      bioelectrochemical systems (BES), but typically with limited efficiency and poor
      controllability. In this study, we discover an important role of uncouplers in
      affecting the microbial energy metabolism and EET. Dose of lower-concentration
      3,3',4',5-tetrachlorosalicylanilide (TCS) in the anolyte promoted the current
      generation and substrate degradation of an MFC inoculated with Shewanella
      oneidensis MR-1. However, higher TCS dosage caused obvious microbial inhibition.
      Our results suggest a previously unknown role of uncouplers in regulating the
      microbial EET. In addition, the underlying mechanisms of such processes are
      investigated. This work broadens our view about the EET behaviors of
      microorganisms in real water environment where uncouplers are usually present,
      and suggests a possible new approach to regulate microbial EET in BES. 

PMID- 25612889
TI  - Microwave Ablation for Twin-Reversed Arterial Perfusion Sequence: A Novel
      Application of Technology.
AB  - INTRODUCTION: Twin-reversed arterial perfusion sequence is a rare complication of
      monochorionic pregnancies that is characterized by the presence of an acardiac
      mass perfused by an apparently normal pump twin. The risk of death to the pump
      twin has led to a range of therapeutic interventions aimed at separating their
      vascular connection. We report a novel application of microwave ablation for
      vessel coagulation in the treatment of twin-reversed arterial perfusion sequence.
      MATERIAL AND METHODS: Microwave ablation has been adopted by surgical
      subspecialties as a superior energy source for vessel and tissue ablation as it
      creates heat without a circuit and has less thermal spread. We describe the use
      of a 2.45-GHz microwave system using a 1.8-mm antenna to coagulate the intra
      abdominal portion of umbilical vessels of the acardiac mass. RESULTS: We report 6
      cases of twin-reversed arterial perfusion sequence treated by microwave ablation.
      All patients were treated with microwave ablation with successful coagulation of
      intra-abdominal umbilical cord vessels of the acardiac mass with cessation of
      flow. DISCUSSION: Microwave ablation is an excellent energy source for vessel
      coagulation due to its thermal properties and can be used effectively in the
      treatment of twin-reversed arterial perfusion sequence.

PMID- 25612891
TI  - miR-17 deregulates a core RUNX1-miRNA mechanism of CBF acute myeloid leukemia.
AB  - BACKGROUND: Core Binding Factor acute myeloid leukemia (CBF-AML) with t(8;21)
      RUNX1-MTG8 or inv(16) CBFB-MYH11 fusion proteins often show upregulation of wild
      type or mutated KIT receptor. However, also non-CBF-AML frequently displays
      upregulated KIT expression. In the first part of this study we show that KIT
      expression can be also upregulated by miR-17, a regulator of RUNX1, the gene
      encoding a CBF subunit. Interestingly, both CBF leukemia fusion proteins and miR
      17, which targets RUNX1-3'UTR, negatively affect a common core RUNX1-miRNA
      mechanism that forces myeloid cells into an undifferentiated, KIT-induced,
      proliferating state. In the second part of this study we took advantage of the
      conservation of the core RUNX1-miRNA mechanism in mouse and human, to
      mechanistically demonstrate in a mouse myeloid cell model that increased KIT
      induced proliferation is per se a mechanism sufficient to delay myeloid
      differentiation. METHODS: Human (U937) or mouse (32D) myeloid clonal lines were
      used, respectively, to test: 1) the effect of RUNX1-MTG8 and CBFB-MYH11 fusion
      proteins, or upregulation of miR-17, on KIT-induced proliferation and myeloid
      differentiation, and 2) the effect of upregulation of KIT-induced proliferation
      per se on myeloid cell differentiation. RESULTS: In the first part of this study
      we found that stable miR-17 upregulation affects, like the CBF-AML fusion
      proteins (RUNX1-MTG8 or CBFB-MYH11), a core RUNX1-miRNA mechanism leading to KIT
      induced proliferation of differentiation-arrested U937 myeloid cells. In the
      second part of the study we harnessed the conservation of this core mechanism in
      human and mouse to demonstrate that the extent of KIT upregulation in 32D mouse
      myeloid cells with wild type RUNX1 can per se delay G-CSF-induced
      differentiation. The integrated information gathered from the two myeloid cell
      models shows that RUNX1 regulates myeloid differentiation not only by direct
      transcriptional regulation of coding and non-coding myeloid differentiation
      functions (e.g. miR-223), but also by modulating KIT-induced proliferation via
      non-coding miRNAs (e.g. miR-221). CONCLUSIONS: The novelty of this study is dual.
      On the one hand, miRNAs (e.g. miR-17) can mimic the effects of CBF-AML fusion
      proteins by affecting a core RUNX1-miRNA mechanism of KIT-induced proliferation
      of undifferentiated myeloid cells. On the other hand, the extent of KIT-induced
      proliferation itself can modulate myeloid differentiation of cells with wild type
      RUNX1 function.

PMID- 25612893
TI  - Tuning the thermoelectric properties of a single-molecule junction by mechanical
      stretching.
AB  - We theoretically investigate, as a function of the stretching, the behaviour of
      the thermoelectric properties - the Seebeck coefficient (S), the electronic heat
      conductance (kappael) and the figure of merit (ZT) - of a molecule-based junction
      composed of a benzene-1,4-dithiolate molecule (BDT) coupled to Au(111) surfaces
      at room temperature. We show that the thermoelectric properties of a single
      molecule junction can be tuned by mechanic stretching. The Seebeck coefficient is
      positive, indicating that it is dominated by the HOMO. Furthermore, it increases
      as the HOMO level, which is associated to the sulphur atom, tends towards
      energies close to the Fermi energy. By modelling the transmission coefficient of
      the system as a single Lorentzian peak, we propose a scheme to obtain the maximum
      ZT of any molecular junction. 

PMID- 25612892
TI  - Overdiagnosis by mammographic screening for breast cancer studied in birth
      cohorts in The Netherlands.
AB  - A drawback of early detection of breast cancer through mammographic screening is
      the diagnosis of breast cancers that would never have become clinically detected.
      This phenomenon, called overdiagnosis, is ideally quantified from the breast
      cancer incidence of screened and unscreened cohorts of women with follow-up until
      death. Such cohorts do not exist, requiring other methods to estimate
      overdiagnosis. We are the first to quantify overdiagnosis from invasive breast
      cancer and ductal carcinoma in situ (DCIS) in birth cohorts using an age-period
      cohort -model (APC-model) including variables for the initial and subsequent
      screening rounds and a 5-year period after leaving screening. Data on the female
      population and breast cancer incidence were obtained from Statistics Netherlands,
      "Stichting Medische registratie" and the Dutch Cancer Registry for women aged 0
      99 years. Data on screening participation was obtained from the five regional
      screening organizations. Overdiagnosis was calculated from the excess breast
      cancer incidence in the screened group divided by the breast cancer incidence in
      presence of screening for women aged 20-99 years (population perspective) and for
      women in the screened-age range (individual perspective). Overdiagnosis of
      invasive breast cancer was 11% from the population perspective and 17% from the
      invited women perspective in birth cohorts screened from age 49 to 74. For
      invasive breast cancer and DCIS together, overdiagnosis was 14% from population
      perspective and 22% from invited women perspective. A major strength of an APC
      model including the different phases of screening is that it allows to estimate
      overdiagnosis in birth cohorts, thereby preventing overestimation. 

PMID- 25612894
TI  - Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled
      fMRI study in healthy subjects.
AB  - BACKGROUND: Impaired sexual function is increasingly recognized as a side effect
      of psychopharmacological treatment. However, underlying mechanisms of action of
      the different drugs on sexual processing are still to be explored. Using
      functional magnetic resonance imaging, we previously investigated effects of
      serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual
      functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic
      and antidopaminergic medication on neural correlates of visual sexual stimulation
      in a new sample of subjects. METHODS: Nineteen healthy heterosexual males (mean
      age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent
      reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and
      placebo were included and studied with functional magnetic resonance imaging
      within a randomized, double-blind, placebo-controlled, within-subjects design
      during an established erotic video-clip task. Subjective sexual functioning was
      assessed using the Massachusetts General Hospital-Sexual Functioning
      Questionnaire. RESULTS: Relative to placebo, subjective sexual functioning was
      attenuated under reboxetine along with diminished neural activations within the
      caudate nucleus. Altered neural activations correlated with decreased sexual
      interest. Under amisulpride, neural activations and subjective sexual functioning
      remained unchanged. CONCLUSIONS: In line with previous interpretations of the
      role of the caudate nucleus in the context of primary reward processing,
      attenuated caudate activation may reflect detrimental effects on motivational
      aspects of erotic stimulus processing under noradrenergic agents.

PMID- 25612895
TI  - Adolescent intermittent ethanol exposure is associated with increased risky
      choice and decreased dopaminergic and cholinergic neuron markers in adult rats.
AB  - BACKGROUND: Binge drinking is prevalent during adolescence and may have effects
      on the adult brain and behavior. The present study investigated whether
      adolescent intermittent ethanol exposure alters adult risky choice and prefrontal
      dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar
      rats. METHODS: Adolescent (postnatal day 28-53) rats were administered 5 g/kg of
      25% (vol/vol) ethanol 3 times/d in a 2-days-on/2-days-off exposure pattern. In
      adulthood, risky choice was assessed in the probability discounting task with
      descending and ascending series of large reward probabilities and after acute
      ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a
      marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices,
      and choline acetyltransferase, a marker of cholinergic neurons, in the basal
      forebrain. RESULTS: All of the rats preferred the large reward when it was
      delivered with high probability. When the large reward became unlikely, control
      rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol
      exposed rats continued to prefer the risky alternative. Acute ethanol had no
      effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic
      cortex only) and choline acetyltransferase immunoreactivity levels were decreased
      in adolescent intermittent ethanol-exposed rats compared with controls. Risky
      choice was negatively correlated with choline acetyltransferase, implicating
      decreased forebrain cholinergic activity in risky choice. CONCLUSIONS: The
      decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity
      suggest that adolescent intermittent ethanol exposure has enduring neural effects
      that may lead to altered adult behaviors, such as increased risky decision
      making. In humans, increased risky decision making could lead to maladaptive,
      potentially harmful consequences.

PMID- 25612896
TI  - BDNF-Val66Met-polymorphism impact on cortical plasticity in schizophrenia
      patients: a proof-of-concept study.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been shown to be a
      moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is
      associated with impairments of cortical plasticity. In patients with
      schizophrenia, reduced neuroplastic responses following non-invasive brain
      stimulation have been reported consistently. Various studies have indicated a
      relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity
      in healthy individuals, but schizophrenia patients have yet to be investigated.
      The aim of this proof-of-concept study was, therefore, to test the impact of the
      BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in
      schizophrenia patients. METHODS: Cortical plasticity was investigated in 22
      schizophrenia patients and 35 healthy controls using anodal and cathodal
      transcranial direct-current stimulation (tDCS) applied to the left primary motor
      cortex. Animal and human research indicates that excitability shifts following
      anodal and cathodal tDCS are related to molecular long-term potentiation and long
      term depression. To test motor-cortical excitability before and after tDCS, well
      established single- and paired-pulse transcranial magnetic stimulation protocols
      were applied. RESULTS: Our analysis revealed increased glutamate-mediated
      intracortical facilitation in met-heterozygotes compared to val-homozygotes at
      baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced
      gamma-amino-butyric-acid-mediated short-interval intracortical inhibition,
      whereas healthy met-heterozygotes displayed the opposite effect. The BDNF
      Val66Met-polymorphism did not influence single-pulse motor-evoked potential
      amplitudes after tDCS. CONCLUSIONS: These preliminary findings support the notion
      of an association of the BDNF-Val66Met-polymorphism with observable alterations
      in plasticity following cathodal tDCS in schizophrenia patients. This indicates a
      complex interaction between inhibitory intracortical interneuron-networks,
      cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and
      validation need to be dedicated to this question to confirm this relationship.

PMID- 25612898
TI  - Intracerebroventricular oxytocin administration in rats enhances object
      recognition and increases expression of neurotrophins, microtubule-associated
      protein 2, and synapsin I.
AB  - Brain oxytocin regulates a variety of social and affiliative behaviors and
      affects also learning and memory. However, mechanisms of its action at the level
      of neuronal circuits are not fully understood. The present study tests the
      hypothesis that molecular factors required for memory formation and synaptic
      plasticity, including brain-derived neurotrophic factor, neural growth factor,
      nestin, microtubule-associated protein 2 (MAP2), and synapsin I, are enhanced by
      central administration of oxytocin. We also investigated whether oxytocin
      enhances object recognition and acts as anxiolytic agent. Therefore, male Wistar
      rats were infused continuously with oxytocin (20 ng/ul) via an osmotic minipump
      into the lateral cerebral ventricle for 7 days; controls were infused with
      vehicle. The object recognition test, open field test, and elevated plus maze
      test were performed on the sixth, seventh, and eighth days from starting the
      infusion. No significant effects of oxytocin on anxious-like behavior were
      observed. The object recognition test showed that oxytocin-treated rats
      significantly preferred unknown objects. Oxytocin treatment significantly
      increased gene expression and protein levels of neurotrophins, MAP2, and synapsin
      I in the hippocampus. No changes were observed in nestin expression. Our results
      provide the first direct evidence implicating oxytocin as a regulator of brain
      plasticity at the level of changes of neuronal growth factors, cytoskeletal
      proteins, and behavior. The data support assumption that oxytocin is important
      for short-term hippocampus-dependent memory.

PMID- 25612897
TI  - Aberrant Monoaminergic System in Thyroid Hormone Receptor-beta Deficient Mice as
      a Model of Attention-Deficit/Hyperactivity Disorder.
AB  - BACKGROUND: Thyroid hormone receptors are divided into 2 functional types:
      TRalpha and TRbeta. Thyroid hormone receptors play pivotal roles in the
      developing brain, and disruption of thyroid hormone receptors can produce
      permanent behavioral abnormality in animal models and humans. METHODS: Here we
      examined behavioralchanges, regional monoamine metabolism, and expression of
      epigenetic modulatory proteins, including acetylated histone H3 and histone
      deacetylase, in the developing brain of TRalpha-disrupted (TRalpha (0/0) ) and
      TRbeta-deficient (TRbeta (-/-) ) mice. Tissue concentrations of dopamine,
      serotonin (5-hydroxytryptamine) and their metabolites in the mesocorticolimbic
      pathway were measured. RESULTS: TRbeta (-/-) mice, a model of attention
      deficit/hyperactivity disorder, showed significantly high exploratory activity
      and reduced habituation, whereas TRalpha (0/0) mice showed normal exploratory
      activity. The biochemical profiles of dopamine and 5-hydroxytryptamine showed
      significantly low dopamine metabolic rates in the caudate putamen and nucleus
      accumbens and overall low 5-hydroxytryptamine metabolic rates in TRbeta (-/-)
      mice, but not in TRalpha (0/0) mice. Furthermore, the expression of acetylated
      histone H3 was low in the dorsal raphe of TRbeta (-/-) mice, and histone
      deacetylase 2/3 proteins were widely increased in the mesolimbic system.
      CONCLUSIONS: These findings suggest that TRbeta deficiency causes dysfunction of
      the monoaminergic system, accompanied by epigenetic disruption during the brain
      maturation process.

PMID- 25612899
TI  - Short-term effects of physiotherapy on ventilation inhomogeneity in cystic
      fibrosis patients with a wide range of lung disease severity.
AB  - BACKGROUND: Lung clearance index (LCI) is increasingly used as a study endpoint
      for therapeutic interventions in cystic fibrosis (CF) patients. We set out to
      assess the effect of chest physiotherapy on ventilation inhomogeneity in
      clinically stable patients with CF lung disease of varying severity. METHODS: In
      29 CF patients (7.3-43.7 years) N2MBW (nitrogen multiple breath washout),
      plethysmography, and spirometry measurements were conducted, followed by 30 min
      of supervised PEP mask chest physiotherapy and repeated measurements 30 min after
      therapy. RESULTS: We observed a mean change in LCI after physiotherapy from 15.00
      to 14.80 (range, -4.84 to 3.37; p=0.578). In seven patients, LCI decreased, and
      in ten patients, LCI increased by >=1. For the whole group, statistically
      significant improvements were seen in Reff, FEV1, FVC, and MEF50. CONCLUSIONS: By
      opening up previously poorly ventilated lung regions, physiotherapy may either
      increase or decrease ventilation inhomogeneity; the short-term effect of
      physiotherapy on LCI appears to be unpredictable.

PMID- 25612900
TI  - Evaluation of mold exposure in cystic fibrosis patients' dwellings and allergic
      bronchopulmonary risk.
AB  - Very few studies have been conducted on cystic fibrosis (CF) patients' exposure
      to the indoor environment and, to our knowledge, there are no studies dealing
      with the link between specific fungal environmental exposure at home and fungal
      colonization resulting in allergic bronchopulmonary aspergillosis (ABPA). Fungal
      exposure of CF adult patients with ABPA (n=4) with fungal sensitization (n=7) and
      with no ABPA (n=5) was assessed in 16 homes by dust sampling with electrostatic
      dust fall collectors (EDCs). Aspergillus fumigatus was specifically quantified by
      real-time quantitative polymerase chain reactions (qPCRs), and A. fumigatus DNA
      concentrations were significantly higher in homes of ABPA patients (p<0.001).
      Results indicate that indoor fungal contamination could be a factor favoring ABPA
      and suggest that environmental surveys could help in preventing fungal risk in CF
      patients. 

PMID- 25612901
TI  - Gambling disorder in older adults: a cross-cultural perspective.
AB  - INTRODUCTION: Gambling disorder (GD) in older adults is significantly increasing
      and became an important public health issue in different countries. However,
      little is known regarding GD in older adults. The prevalence and acceptance of
      gambling vary among different cultures and this raises the question of how and to
      what extent culture affects older gamblers. The majority of the important studies
      regarding GD in older adults have been conducted mainly in Anglo-Saxon cultures
      and little information is available regarding GD in other cultures. The objective
      of this paper is to perform the first standardized cross-cultural comparison
      regarding older adults presenting GD. METHODS: The total studied sample involved
      170 subjects: 89 from the Brazilian (BR) sample and 81 from the American (US)
      sample. It consisted of 67 men and 103 women (average age=64.42, standard
      deviation=+/-3.86). They were evaluated for socio-demographics, gambling behavior
      variables and psychiatric antecedents. RESULTS: Overall, there were significant
      differences between BR and US older adult gamblers in marital status, onset of
      gambling activity, onset of GD and urge scores. DISCUSSION: This study showed
      that there are important differences in gambling course, gambling behavior and
      personal antecedents between two samples of older adults presenting GD from
      countries with different social-cultural background. It weakens the possibility
      of generalization of results found in Anglo-Saxon countries to other cultures and
      reinforces for the need for development of research on GD in older adults outside
      the Anglo-Saxon culture.

PMID- 25612902
TI  - External validity of the Symptom Assessment-45 Questionnaire (SA-45) in a
      clinical sample.
AB  - This study seeks to evaluate the construct validity of the Symptom Assessment-45
      by investigating the instrument's correlation with selected scales from the
      Personality Assessment Inventory and life-event data in a sample of 93
      psychiatric patients. The life-event data used in the study included: education
      and employment, as well as history of suicide attempts, psychiatric
      hospitalizations, medical problems, hallucinations, and paranoid ideation.
      Bivariate correlations were computed to explore the associations among the SA-45
      scales and the validity criteria. The results indicated that the SA-45 scales
      demonstrated adequate convergent and divergent validity with target scales from
      the PAI. They were also found to be meaningfully associated with a variety of
      life event variables. These findings add to the emerging body of evidence
      corroborating the convergent and discriminant validity of the SA-45. 

PMID- 25612903
TI  - The use of nanoparticles as a promising therapeutic approach in cancer
      immunotherapy.
AB  - Cancer is one of the most important causes of death all over the world, which has
      not yet been treated efficiently. Although several therapeutic approaches have
      been used, some side effects such as toxicity and drug resistance have been
      observed in patients, particularly with chemotherapy. The nanoparticle-mediated
      drug delivery systems (DDS) have a great potential to improve cancer treatment by
      transferring therapeutic factors directly to the tumor site. Such a treatment
      significantly decreases the adverse effects associated with cancer therapy on
      healthy tissues. Two main strategies, including passive and active methods, have
      been considered to be effective techniques which can target the drugs to the
      tumor sites. The current review sheds some light on the place of nanotechnology
      in cancer drug delivery, and introduces nanomaterials and their specific
      characteristics that can be used in tumor therapy. Moreover, passive and active
      targeting approaches focus on antibodies, particularly single chain variable
      fragments (scFv), as a novel and important ligand in a drug delivery system. 

PMID- 25612905
TI  - SiRNA nanotherapeutics _the panacea of diseases?
AB  - RNAi based therapeutics hold s great promises to be an efficient strategy of the
      anti-gene realm in context of its therapeutic applications; however, despite
      significant potentials, its full efficacy cannot be realized in real sense owing
      to various confronts that plague its advancement. Efforts need to be driven for
      the development of specific and efficacious strategies to subdue some of their
      crucial constraints towards successes in clinics. This article will present the
      major impediments that encumber successful translation of siRNA concept into
      reality and the ongoing research endeavours to get through those stumbling blocks
      along with their inadequacies. 

PMID- 25612904
TI  - A comprehensive database of Duchenne and Becker muscular dystrophy patients (0-18
      years old) in East China.
AB  - BACKGROUND: Currently, there is no cure for Duchenne and Becker muscular
      dystrophies (DMD/BMD). However, clinical trials with new therapeutic strategies
      are being conducted or considered. A comprehensive database is critical for
      patient recruitment and efficacy evaluation. China has the largest population,
      yet, no comprehensive database for DMD/BMD is available. Our study registered the
      data of the DMD/BMD patients in East China. METHODS: A modified registry form of
      Remudy ( http://www.remudy.jp/ ) was applied to Chinese DMD/BMD patients through
      the outpatient clinic at Children's Hospital of Fudan University, Shanghai during
      the period of August 2011 to December 2013. The data included geographic
      distribution of patients, age at diagnosis, clinical manifestation, genetic
      analysis and treatment status. RESULTS: 194 DMD and 35 BMD patients were
      registered. Most patients lived in East China, namely Jiangsu province, Anhui
      province, Zhejiang province, Jiangxi province, Shanghai, Fujian province and
      Shandong province. All individuals aged less than 18 years (age limit to a
      children's hospital). Diagnosis was made for a majority of patients during the
      age of 3-4 (16.6%) and 7-8 (14.8%) years old. Exon deletion was the most frequent
      genetic mutations (65.5% and 74.3%) followed by point mutations (14.4% and
      11.4%), duplications (9.8% and 8.6%) and small insertion/deletion (9.3% and 2.9%)
      for DMD and BMD, respectively. 82.5% of DMD registrants were ambulatory, and all
      the BMD registrants were able to walk. 26.3% of DMD registrants have been treated
      with steroids. Cardiac functions were examined for 46.4% DMD boys and 45.7% BMD
      boys and respiratory functions were examined for 18.6% DMD boys and 14.3% BMD
      boys. Four boys with abnormal cardiac function were prescribed for treatment with
      cardiac medicine. 33.2% of DMD patients are eligible for exon skipping therapy,
      and among them 9.2% and 4.3% patients are eligible for skipping exon 51 and 53,
      respectively. CONCLUSIONS: The database is the first linking accurate genetic
      diagnosis with clinical manifestation and treatment status of dystrophinopathy
      patients in East China. It provides comprehensive information essential for
      further patient management, especially for promotion of international cooperation
      in developing experimental therapies such as exon skipping and read-through of
      nonsense mutations targeting a subgroup of DMD patient population.

PMID- 25612907
TI  - Effects of oatmeal and corn flakes cereal breakfasts on satiety, gastric
      emptying, glucose, and appetite-related hormones.
AB  - OBJECTIVE: The extent to which different types of breakfasts affect appetite and
      food intake is unclear. To assess the satiety effects of a high-fiber cereal, we
      compared oatmeal, isocaloric corn flakes, and water. SUBJECTS/METHODS: Thirty-six
      subjects (18 lean, 18 overweight) were assigned to three conditions in a
      randomized sequence on different days. Ratings of hunger and fullness were
      obtained concurrently with blood samples for measuring concentrations of glucose,
      insulin, glucagon, leptin, and acetaminophen (gastric emptying tracer). Appetite
      was assessed by calculating the area under the curve (AUC) for fullness and
      hunger, and by measuring food intake of an ad libitum lunch meal at 180 min.
      RESULTS: Lunch meal intake was lowest after consuming oatmeal (p < 0.00001),
      which was lower for overweight subjects than lean subjects (p = 0.007). Fullness
      AUC was greatest (p = 0.00001), and hunger AUC lowest (p < 0.001) after consuming
      oatmeal. At 180 min, blood glucose was lowest after the corn flakes (p = 0.0001).
      Insulin AUC was greater for both cereals than water (p < 0.00001). Leptin AUC and
      glucagon AUC values did not differ between conditions. Acetaminophen
      concentrations peaked latest after consuming oatmeal (p = 0.046), reflecting
      slower gastric emptying. CONCLUSIONS: Satiety was greater and ad libitum test
      meal intake lower after consuming oatmeal than after corn flakes, especially in
      the overweight subjects.

PMID- 25612906
TI  - Glycomic signatures on serum IgGs for prediction of postvaccination response.
AB  - Millions of individuals are vaccinated worldwide each year to stimulate their
      adaptive immune systems to produce protective antibodies and T-cell response
      against pathogens. Since glycosylation of the Fc region of immunoglobulin G (IgG)
      can be influenced by the host's immune status, it was inferred that glycosylation
      profile of IgG might be altered as a result of the immune response. Therefore,
      subclass-specific glycosylation profiles of serum IgGs from 26 healthy adults
      before and after vaccination with a trivalent subunit influenza virus vaccine
      were comprehensively analyzed to explore glycomic signatures for vaccination. The
      results showed that no significant changes in the glycosylation of total IgGs
      took place before and after vaccination, but distinct glycosylation profiles in
      responders (fourfold or more increase of HI titer after vaccination) and
      nonresponders (less than fourfold increase of HI titer) were observed. This
      difference between the responders and nonresponders occurred even in the resting
      state. On the basis of variable importance parameters, glycosylation markers that
      distinguish responders from nonresponders were identified. These markers can be
      used as molecular signatures to predict antibody titers after vaccination. This
      is the first study of serum IgG glycosylation profiles in healthy adults
      receiving a trivalent inactivated influenza vaccine. 

PMID- 25612909
TI  - MuSK: a new target for lethal fetal akinesia deformation sequence (FADS).
AB  - BACKGROUND: Fetal akinesia deformation sequence syndrome (FADS, OMIM 208150) is
      characterised by decreased fetal movement (fetal akinesia) as well as
      intrauterine growth restriction, arthrogryposis, and developmental anomalies (eg,
      cystic hygroma, pulmonary hypoplasia, cleft palate, and cryptorchidism).
      Mutations in components of the acetylcholine receptor (AChR) pathway have
      previously been associated with FADS. METHODS AND RESULTS: We report on a family
      with recurrent fetal loss, where the parents had five affected fetuses/children
      with FADS and one healthy child. The fetuses displayed no fetal movements from
      the gestational age of 17 weeks, extended knee joints, flexed hips and elbows,
      and clenched hands. Whole exome sequencing of one affected fetus and the parents
      was performed. A novel homozygous frameshift mutation was identified in muscle,
      skeletal receptor tyrosine kinase (MuSK), c.40dupA, which segregated with FADS in
      the family. Haplotype analysis revealed a conserved haplotype block suggesting a
      founder mutation. MuSK (muscle-specific tyrosine kinase receptor), a component of
      the AChR pathway, is a main regulator of neuromuscular junction formation and
      maintenance. Missense mutations in MuSK have previously been reported to cause
      congenital myasthenic syndrome (CMS) associated with AChR deficiency.
      CONCLUSIONS: To our knowledge, this is the first report showing that a mutation
      in MuSK is associated with FADS. The results support previous findings that CMS
      and/or FADS are caused by complete or severe functional disruption of components
      located in the AChR pathway. We propose that whereas milder mutations of MuSK
      will cause a CMS phenotype, a complete loss is lethal and will cause FADS.

PMID- 25612910
TI  - Evaluation of somatic mutations in tibial pseudarthrosis samples in
      neurofibromatosis type 1.
AB  - BACKGROUND: Tibial pseudarthrosis is associated with neurofibromatosis type 1
      (NF1) and there is wide clinical variability of the tibial dysplasia in NF1,
      suggesting the possibility of genetic modifiers. Double inactivation of NF1 is
      postulated to be necessary for the development of tibial pseudarthrosis, but
      tissue or cell of origin of the 'second hit' mutation remains unclear. METHODS:
      Exome sequencing of different sections of surgically resected NF1 tibial
      pseudarthrosis tissue was performed and compared to germline (peripheral blood).
      RESULTS: A germline NF1 splice site mutation (c.61-2A>T, p.L21 M68del) was
      identified from DNA extracted from peripheral blood. Exome sequencing of DNA
      extracted from tissue removed during surgery of the tibial pseudarthrosis showed
      a somatic mutation of NF1 (c.3574G>T, p.E1192*) in the normal germline allele.
      Further analysis of different regions of the tibial pseudarthrosis sample showed
      enrichment of the somatic mutation in the soft tissue within the pseudarthrosis
      site and absence of the somatic mutation in cortical bone. In addition, a
      germline variant in PTPN11 (c.1658C>T, p.T553M), a gene involved in the RAS
      signal transduction pathway was identified, although the clinical significance is
      unknown. CONCLUSIONS: Given that the NF1 somatic mutation was primarily detected
      in the proliferative soft tissue at the pseudarthrosis site, it is likely that
      the second hit occurred in mesenchymal progenitors from the periosteum. These
      results are consistent with a defect of differentiation, which may explain why
      the mutation is found in proliferative cells and not within cortical bone tissue,
      as the latter by definition contains mostly mature differentiated osteoblasts and
      osteocytes.

PMID- 25612908
TI  - Regulation of mitochondrial transport in neurons.
AB  - Mitochondria are cellular power plants that supply ATP to power various
      biological activities essential for neuronal growth, survival, and function. Due
      to unique morphological features, neurons face exceptional challenges to maintain
      ATP and Ca(2+) homeostasis. Neurons require specialized mechanisms distributing
      mitochondria to distal areas where energy and Ca(2+) buffering are in high
      demand, such as synapses and axonal branches. These distal compartments also
      undergo development- and activity-dependent remodeling, thereby altering
      mitochondrial trafficking and distribution. Mitochondria move bi-directionally,
      pause briefly, and move again, frequently changing direction. In mature neurons,
      only one-third of axonal mitochondria are motile. Stationary mitochondria serve
      as local energy sources and buffer intracellular Ca(2+). The balance between
      motile and stationary mitochondria responds quickly to changes in axonal and
      synaptic physiology. Furthermore, neurons are postmitotic cells surviving for the
      lifetime of the organism; thus, mitochondria need to be removed when they become
      aged or dysfunction. Mitochondria also alter their motility under stress
      conditions or when their integrity is impaired. Therefore, regulation of
      mitochondrial transport is essential to meet altered metabolic requirements and
      to remove aged and damaged mitochondria or replenish healthy ones to distal
      terminals. Defects in mitochondrial transport and altered distribution are
      implicated in the pathogenesis of several major neurological disorders. Thus,
      research into the mechanisms regulating mitochondrial motility is an important
      emerging frontier in neurobiology. This short review provides an updated overview
      on motor-adaptor machineries that drive and regulate mitochondrial transport and
      docking receptors that anchor axonal mitochondria in response to the changes in
      synaptic activity, metabolic requirement, and altered mitochondrial integrity.
      The review focuses on microtubule (MT)-based mitochondrial trafficking and
      anchoring. Additional insight from different perspectives can be found in other
      in-depth reviews. 

PMID- 25612911
TI  - Transmission of germline TP53 mutations from male carriers to female partners.

PMID- 25612912
TI  - A novel X-linked trichothiodystrophy associated with a nonsense mutation in
      RNF113A.
AB  - BACKGROUND: Trichothiodystrophy (TTD) is a group of rare autosomal recessive
      disorders that variably affect a wide range of organs derived from the
      neuroectoderm. The key diagnostic feature is sparse, brittle, sulfur deficient
      hair that has a 'tiger-tail' banding pattern under polarising light microscopy.
      PATIENTS AND METHODS: We describe two male cousins affected by TTD associated
      with microcephaly, profound intellectual disability, sparse brittle hair, aged
      appearance, short stature, facial dysmorphism, seizures, an immunoglobulin
      deficiency, multiple endocrine abnormalities, cerebellar hypoplasia and partial
      absence of the corpus callosum, in the absence of cellular photosensitivity and
      ichthyosis. Obligate female carriers showed 100% skewed X-chromosome
      inactivation. Linkage analysis and Sanger sequencing of 737 X-chromosome exons
      and whole exome sequencing was used to find the responsible gene and mutation.
      RESULTS: Linkage analysis localised the disease allele to a 7.75 Mb interval from
      Xq23-q25. We identified a nonsense mutation in the highly conserved RNF113A gene
      (c.901 C>T, p.Q301*). The mutation segregated with the disease in the family and
      was not observed in over 100,000 control X chromosomes. The mutation markedly
      reduced RNF113A protein expression in extracts from lymphoblastoid cell lines
      derived from the affected individuals. CONCLUSIONS: The association of RNF113A
      mutation with non-photosensitive TTD identifies a new locus for these disorders
      on the X chromosome. The extended phenotype within this family includes
      panhypopituitarism, cutis marmorata and congenital short oesophagus.

PMID- 25612913
TI  - Genetic susceptibility to dental caries differs between the sexes: a family-based
      study.
AB  - Many of the factors affecting susceptibility to dental caries are likely
      influenced by genetics. In fact, genetics accounts for up to 65% of inter
      individual variation in dental caries experience. Sex differences in dental
      caries experience have been widely reported, with females usually exhibiting a
      higher prevalence and severity of disease across all ages. The cause for this sex
      bias is currently uncertain, although it may be partly due to the differential
      effects of genetic factors between the sexes: gene-by-sex interactions. In this
      family based study (N = 2,663; 740 families; ages 1-93 years), we assessed dental
      caries via intra-oral examination and generated six indices of caries experience
      (DMFS, dfs, and indices of both pit-and-fissure surface caries and smooth surface
      caries in both primary and permanent dentitions). We used likelihood-based
      methods to model the variance in caries experience conditional on the expected
      genetic sharing among relatives in our sample. This modeling framework allowed us
      to test two lines of evidence for gene-by-sex interactions: (1) whether the
      magnitude of the cumulative effect of genes differs between the sexes, and (2)
      whether different genes are involved. We observed significant evidence of gene-by
      sex interactions for caries experience in both the primary and permanent
      dentitions. In the primary dentition, the magnitude of the effect of genes was
      greater in males than females. In the permanent dentition, different genes may
      play important roles in each of the sexes. Overall, this study provides the first
      direct evidence that sex differences in dental caries experiences may be
      explained, in part, by gene-by-sex interactions.

PMID- 25612914
TI  - Disability in moderate chronic obstructive pulmonary disease: prevalence, burden
      and assessment - results from a real-life study.
AB  - BACKGROUND: The role of disability and its association with patient-reported
      outcomes in the nonsevere forms of chronic obstructive pulmonary disease (COPD)
      has never been explored. OBJECTIVES: The aim of this study was to assess, in a
      cross-sectional real-life study, the prevalence and degree of disability in
      moderate COPD patients and to assess its association with health status, illness
      perception, risk of death and well-being. METHODS: Moderate COPD outpatients
      attending scheduled visits were involved in a quantitative research program using
      a questionnaire-based data collection method. RESULTS: Out of 694 patients, 17.4%
      were classified as disabled and 47.6% reported the loss of at least one relevant
      function of daily living. Disabled patients did not differ from nondisabled
      patients in terms of working status (p = 0.06), smoking habits (p = 0.134) and
      ongoing treatment (p = 0.823); however, the former showed a significantly higher
      disease burden as measured by illness perception, health status and well-being.
      The stepwise regression analysis showed that the modified Medical Research
      Council (mMRC) score was the most relevant factor related to COPD disability (F =
      38.248; p = 0.001). Patient stratification was possible according to the forced
      expiratory volume in 1 s (FEV1) value and an mMRC score >=2, which identified
      disabled patients, whereas the mMRC values were differently associated with the
      risk of disability. CONCLUSION: A significant proportion of individuals with
      moderate COPD reported a limitation of daily life functions, with dyspnea being
      the most relevant factor inducing disability. Adding the evaluation of patient
      reported outcomes to lung function assessment could facilitate the identification
      of disabled patients.

PMID- 25612915
TI  - Interaction of von Willebrand factor with platelets and the vessel wall.
AB  - The initiation of thrombus formation at sites of vascular injury to secure
      haemostasis after tissue trauma requires the interaction of surface-exposed von
      Willebrand factor (VWF) with its primary platelet receptor, the glycoprotein (GP)
      Ib-IX-V complex. As an insoluble component of the extracellular matrix (ECM) of
      endothelial cells, VWF can directly initiate platelet adhesion. Circulating
      plasma VWF en-hances matrix VWF activity by binding to structures that become
      exposed to flowing blood, notably collagen type I and III in deeper layers of the
      vessel along with microfibrillar collagen type VI in the subendothelium.
      Moreover, plasma VWF is required to support platelet-to-platelet adhesion - i. e.
      aggregation - which promotes thrombus growth and consolidation. For these
      reasons, understanding how plasma VWF interaction with platelet receptors is
      regulated, particularly any distinctive features of GPIb binding to soluble as
      opposed to immobilized VWF, is of paramount importance in vascular biology. This
      brief review will highlight knowledge acquired and key problems that remain to be
      solved to elucidate fully the role of VWF in normal haemostasis and pathological
      thrombosis. 

PMID- 25612917
TI  - The effects of SP110's associated genes on fresh cavitary pulmonary tuberculosis
      in Han Chinese population.
AB  - SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate
      the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on
      pathological progression of MTB infection, an association study with 424 patients
      of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed.
      Moreover, classification and regression tree and multifactor dimensionality
      reduction were employed to explore the effects of gene-gene interactions on
      cavitary PTB. The results indicated that both the heterozygous genotype GC and
      homozygous genotype CC in rs3809849 had significant effects on the risk of PTB
      (OR 1.42, 95 % CI 1.06-1.92, p 0.019; OR 1.55, 95 % CI 1.04-2.33, p = 0.033,
      respectively), and heterozygous genotype CT in rs9061 also had similar effects
      (OR 1.43, 95 % CI 1.07-1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A
      were also significantly associated with cavitary PTB (p = 0.00046 and 0.039,
      respectively), while rs9061 in SP110 had no such association (p = 0.06931) except
      its significant association with non-cavitary PTB (p = 0.0093). The interaction
      of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44
      12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic
      risk factor for cavitary PTB and play important effects on its whole progress. 

PMID- 25612920
TI  - Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed
      dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.
AB  - Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I
      (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a
      novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T
      lymphocyte (CTL) response that has been implicated in anti-ATL effects, and
      conducted a pilot study to investigate its safety and efficacy. Three previously
      treated ATL patients, classified as intermediate- to high-risk, were
      subcutaneously administered with the vaccine, consisting of autologous dendritic
      cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all
      patients, the performance status improved after vaccination without severe
      adverse events, and Tax-specific CTL responses were observed with peaks at 16-20
      weeks. Two patients achieved partial remission in the first 8 weeks, one of whom
      later achieved complete remission, maintaining their remission status without any
      additional chemotherapy 24 and 19 months after vaccination, respectively. The
      third patient, whose tumour cells lacked the ability to express Tax at biopsy,
      obtained stable disease in the first 8 weeks and later developed slowly
      progressive disease although additional therapy was not required for 14 months.
      The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC
      vaccine is a safe and promising immunotherapy for ATL. 

PMID- 25612918
TI  - Site-selective nucleation and controlled growth of gold nanostructures in tobacco
      mosaic virus nanotubulars.
AB  - Site-selective biomineralization of Au nanostructures in the interior channel of
      Tobacco Mosaic Virus (TMV) is achieved by mutating threonine 103 in TMV to
      cysteine (T103C-TMV) to introduce the strong coordination interaction between the
      arrayed sulfhydryl ligands and gold species. By finely tuning the reaction
      conditions, Au nanoparticle chains and Au nanorods are successfully and
      exclusively synthesized inside the T103C-TMV nanotubes. 

PMID- 25612921
TI  - Amino-Nogo inhibits optic nerve regeneration and functional recovery via the
      integrin alphav signaling pathway in rats.
AB  - BACKGROUND: Nogo-A, a major myelin-associated inhibitor, can inhibit injured
      optic nerve regeneration. However, whether Amino-Nogo is the most important
      functional domain of Nogo-A remains unknown. This study aimed to identify the
      role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino
      Nogo-integrin alphav signaling pathway in vivo. METHODS: Sprague-Dawley rats with
      optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo
      66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat
      Amino-Nogo-A protein (?20) into the vitreous cavity to knock down Nogo-A, inhibit
      Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC)
      density, axon regeneration and the pattern of NPN of visual electrophysiology
      (flash visual evoked potentials [F-VEP]) at different times post-injury were
      investigated. RESULTS: Our study revealed a lower RGC survival rate; shorter
      axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2
      amplitudes in the Delta20 group, and Delta20 treatment significantly attenuated
      integrin alphav expression and phosphorylated focal adhesion kinase (p-FAK)
      levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival
      rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1
      P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin
      alphav expression and p-FAK levels. Nepl-40 treatment did not alter integrin
      alphav expression. In addition, there was no significant change in integrin
      alpha5 in any group. CONCLUSION: These results suggest that the integrin
      signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve
      regeneration and functional recovery, and that the integrin subunit involved
      might be integrin alphav but not integrin alpha5.

PMID- 25612916
TI  - Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific
      inhibitor.
AB  - The contemporary use of nanomedicines for cancer treatment has been largely
      limited to serving as carriers for existing therapeutic agents. Here, we provide
      definitive evidence that, the metallofullerenol nanomaterial Gd@C82(OH)22, while
      essentially not toxic to normal mammary epithelial cells, possesses intrinsic
      inhibitory activity against triple-negative breast cancer cells. Gd@C82(OH)22
      blocks epithelial-to-mesenchymal transition with resultant efficient elimination
      of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation
      and metastasis. In normoxic conditions, Gd@C82(OH)22 mediates these effects by
      blocking TGF-beta signalling. Moreover, under hypoxic conditions found in the
      tumour microenvironment, cellular uptake of Gd@C82(OH)22 is facilitated where it
      functions as a bi-potent inhibitor of HIF-1alpha and TGF-beta activities,
      enhancing CSC elimination. These studies indicate that nanomaterials can be
      engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a
      kind of non-toxic CSC specific inhibitors with significant therapeutic potential.

PMID- 25612922
TI  - The Impact of Gender Differences in Attitudes and Beliefs Concerning HBV
      Vaccination and Screening in the Lao Community.
AB  - Liver cancer incidence is increasing among Asian Americans. Laotians in the US
      have greater risk of liver cancer death compared to other Asian American groups.
      However, ethnicity is not the only disparity; Laotian men are at increased risk
      of liver cancer compared to Laotian women. Use of hepatitis B virus (HBV)
      vaccination and screening is low among Laotians. The impact of gender differences
      in attitudes and beliefs concerning HBV vaccination and screening is unknown.
      This secondary analysis of a cross-sectional community-based participatory
      research study. Although men were more likely to believe that infection with HBV
      is preventable, and treatable, causes liver cancer, and that healthy persons
      should be vaccinated, of those who thought people should get vaccinated, women
      were four times more likely to receive vaccine than men (adj. OR 4.0, CI 1.2-19).
      Understanding and addressing gender differences may increase HBV screening and
      vaccination uptake, thus reducing disparities within the Laotian community. 

PMID- 25612923
TI  - Acculturation and Drug Use Stigma Among Latinos and African Americans: An
      Examination of a Church-Based Sample.
AB  - Substance use patterns among Latinos likely reflect changes in attitudes
      resulting from acculturation, but little is known about Latinos' attitudes
      regarding drug addiction. We surveyed a church-based sample of Latinos and
      African Americans (N = 1,235) about attitudes toward drug addiction and socio
      demographics. Linear regression models compared Latino subgroups with African
      Americans. In adjusted models, Latinos had significantly higher drug addiction
      stigma scores compared to African Americans across all subgroups (US-born
      Latinos, beta = 0.22, p < .05; foreign-born Latinos with high English
      proficiency, beta = 0.30, p < .05; and foreign-born Latinos with low English
      proficiency, beta = 0.49, p < .001). Additionally, Latinos with low English
      proficiency had significantly higher mean levels of drug use stigma compared
      Latinos with high proficiency (both foreign-born and US-born). In this church
      affiliated sample, Latinos' drug addiction stigma decreases with acculturation,
      but remains higher among the most acculturated Latinos compared to African
      Americans. These attitudes may pose a barrier to treatment for Latino drug users.

PMID- 25612924
TI  - Genome-wide identification and characterization of the bHLH gene family in
      tomato.
AB  - BACKGROUND: The basic helix-loop-helix (bHLH) proteins are a large superfamily of
      transcription factors, and play a central role in a wide range of metabolic,
      physiological, and developmental processes in higher organisms. Tomato is an
      important vegetable crop, and its genome sequence has been published recently.
      However, the bHLH gene family of tomato has not been systematically identified
      and characterized yet. RESULTS: In this study, we identified 159 bHLH protein
      encoding genes (SlbHLH) in tomato genome and analyzed their structures. Although
      bHLH domains were conserved among the bHLH proteins between tomato and
      Arabidopsis, the intron sequences and distribution of tomato bHLH genes were
      extremely different compared with Arabidopsis. The gene duplication analysis
      showed that 58.5% and 6.3% of SlbHLH genes belonged to low-stringency and high
      stringency duplication, respectively, indicating that the SlbHLH genes are mainly
      generated via short low-stringency region duplication in tomato. Subsequently, we
      classified the SlbHLH genes into 21 subfamilies by phylogenetic tree analysis,
      and predicted their possible functions by comparison with their homologous genes
      of Arabidopsis. Moreover, the expression profile analysis of SlbHLH genes from 10
      different tissues showed that 21 SlbHLH genes exhibited tissue-specific
      expression. Further, we identified that 11 SlbHLH genes were associated with
      fruit development and ripening (eight of them associated with young fruit
      development and three with fruit ripening). The evolutionary analysis revealed
      that 92% SlbHLH genes might be evolved from ancestor(s) originated from early
      land plant, and 8% from algae. CONCLUSIONS: In this work, we systematically
      identified SlbHLHs by analyzing the tomato genome sequence using a set of
      bioinformatics approaches, and characterized their chromosomal distribution, gene
      structures, duplication, phylogenetic relationship and expression profiles, as
      well predicted their possible biological functions via comparative analysis with
      bHLHs of Arabidopsis. The results and information provide a good basis for
      further investigation of the biological functions and evolution of tomato bHLH
      genes.

PMID- 25612925
TI  - Health resource variability in the achievement of optimal performance and
      clinical outcome in ischemic heart disease.
AB  - A disparity between evidence and practice in the management of ischemic heart
      disease is frequently observed. Guideline adherence and clinical outcomes are
      influenced by system, provider, and patient factors. Recently, performance
      improvement measures for cardiovascular disease have gained a lot of popularity
      worldwide. These measures may facilitate the uptake of evidence-based
      recommendations and improve patient outcomes. While apparently valid as quality
      metrics, their impacts on clinical outcomes remain limited and are areas of
      further research. Several methods for optimizing performance have been instituted
      and essentially involve three different approaches-improvement in the reporting
      of data on guideline adherence, providing infrastructure and tools, and providing
      incentives to improve guideline adherence. Public reporting of quality metrics
      and "pay-for-performance" are some novel performance improvement tools. The
      impact of these approaches on patient outcomes will be pivotal in improving
      cardiovascular outcomes in the future.

PMID- 25612926
TI  - Ultra-low-noise EEG/MEG systems enable bimodal non-invasive detection of spike
      like human somatosensory evoked responses at 1 kHz.
AB  - Non-invasive EEG detection of very high frequency somatosensory evoked potentials
      featuring frequencies up to and above 1 kHz has been recently reported. Here, we
      establish the detectability of such components by combined low-noise EEG/MEG. We
      recorded SEP/SEF simultaneously using median nerve stimulation in five healthy
      human subjects inside an electromagnetically shielded room, combining a low-noise
      EEG custom-made amplifier (4.7 nV/?Hz) and a custom-made single-channel low-noise
      MEG (0.5 fT/?Hz @ 1 kHz). Both, low-noise EEG and MEG revealed three spectrally
      distinct and temporally overlapping evoked components: N20 (<100 Hz), sigma-burst
      (450-750 Hz), and kappa-burst (850-1200 Hz). The two recording modalities showed
      similar relative scaling of signal amplitude in all three frequencies domains
      (EEG [10 nV] ? MEG [1 fT]). Pronounced waveform (peak-by-peak) overlap of EEG and
      MEG signals is observed in the sigma band, whereas in the kappa band overlap was
      only partial. A decreasing signal-to-noise ratio (SNR; calculated for n = 12.000
      averages) from sigma to kappa components characterizes both, electric and
      magnetic field recordings: Sigma-band SNR was 12.9  +/-  5.5/19.8  +/-  12.6 for
      EEG/MEG, and kappa-band SNR at 3.77  +/-  0.8/4.5  +/-  2.9. High-frequency
      performance of a tailor-made MEG matches closely with simultaneously recorded low
      noise EEG for the non-invasive detection of somatosensory evoked activity at and
      above 1 kHz. Thus, future multi-channel dual-mode low-noise technology could
      offer complementary views for source reconstruction of the neural generators
      underlying such high-frequency responses, and render neural high-frequency
      processes related to multi-unit spike discharges accessible in non-invasive
      recordings. 

PMID- 25612927
TI  - Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up
      study.
AB  - BACKGROUND: Course and predictors of persistence of attention deficit
      hyperactivity disorder (ADHD) in adults are still largely unknown.
      Neurobiological and clinical differences between child and adult ADHD raise the
      need for follow-up studies of patients diagnosed during adulthood. This study
      investigates predictors of ADHD persistence and the possibility of full remission
      7 years after baseline assessment. METHOD: A 7-year follow-up study of adults
      with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables
      from different domains (social demographics, co-morbidities, temperament,
      medication status, ADHD measures) were explored with the aim of finding potential
      predictors of ADHD persistence. RESULTS: Retention rate was 66% (n = 227).
      Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD
      criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of
      changes in co-morbidity or cognitive demand profiles. Baseline predictors of
      diagnostic persistence were higher number of inattention symptoms [odds ratio
      (OR) 8.05, 95% confidence interval (CI) 2.54-25.45, p < 0.001], number of
      hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04-1.34, p = 0.01),
      oppositional defiant disorder (OR 3.12, 95% CI 1.20-8.11, p = 0.02), and social
      phobia (OR 3.59, 95% CI 1.12-11.47, p = 0.03). CONCLUSIONS: Despite the stage of
      brain maturation in adults suggests stability, approximately one third of the
      sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early,
      middle or older adulthood. Although full remission is less common than in
      childhood, it should be considered as a possible outcome among adults.

PMID- 25612930
TI  - Corrigendum.

PMID- 25612928
TI  - Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic
      markers.
AB  - PURPOSE: Fish oil (FO) elicits diverse beneficial effects. Reduction in or
      prevention of body mass (BM) gain in animal models may be associated with
      modulation of brown adipose tissue (BAT). We aimed to evaluate the effects of
      different high-fat diets with FO on BAT metabolism and thermogenic markers.
      METHODS: C57BL/6 male mice (3-month-old) were fed different diets during 8 weeks:
      standard-chow diet (SC 10% fat), high-fat lard diet (HF-L 50% fat), high-fat lard
      plus FO diet (HF-L+FO 50% fat), and high-fat FO diet (HF-FO 50% fat). We
      evaluated BM and performed an oral glucose tolerance test. At euthanasia, plasma
      was collected for leptin, and triacylglycerol measurement and interscapular BAT
      was dissected and stored for molecular analyses. RESULTS: HF-L group showed
      elevated BM; glucose intolerance associated with diminished TC10 and GLUT4
      expressions; hypertriglyceridemia associated with increased CD36 and diminished
      CPT1 expression; elevated expression of pro-inflammatory cytokines; and reduced
      PPAR expression. Furthermore, these animals showed hyperleptinemia with increased
      expression of thermogenic markers (beta3-AR, PGC1alpha, and UCP1). Conversely, HF
      L+FO and HF-FO groups showed reduced BM gain with regularization of glucose
      tolerance and triglyceridemia, GLUT4, TC10, CD36, CPT1, and cytokines
      expressions. Both groups exhibited elevated PPAR and thermogenic markers
      expression in a dose-dependent way. CONCLUSIONS: FO improves metabolic profile
      and upregulates thermogenic markers, suggesting an elevated thermogenesis that
      leads to reduced BM gain.

PMID- 25612929
TI  - Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle
      energy metabolism and physical performance in male vegetarians.
AB  - PURPOSE: More than 95% of the body carnitine is located in skeletal muscle, where
      it is essential for energy metabolism. Vegetarians ingest less carnitine and
      carnitine precursors and have lower plasma carnitine concentrations than
      omnivores. Principle aims of the current study were to assess the plasma and
      skeletal muscle carnitine content and physical performance of male vegetarians
      and matched omnivores under basal conditions and after L-carnitine
      supplementation. RESULTS: Sixteen vegetarians and eight omnivores participated in
      this interventional study with oral supplementation of 2 g L-carnitine for 12
      weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma
      carnitine concentration, but maintained skeletal muscle carnitine stores compared
      to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents
      were also not different from omnivores. Maximal oxygen uptake (VO2max) and
      workload (P max) per bodyweight (bicycle spiroergometry) were not significantly
      different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for
      1 h) revealed no significant differences between vegetarians and omnivores
      (respiratory exchange ratio, blood lactate and muscle metabolites).
      Supplementation with L-carnitine significantly increased the total plasma
      carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle
      carnitine content in vegetarians (13%). Despite this increase, P max and VO2max
      as well as muscle phosphocreatine, lactate and glycogen were not significantly
      affected by carnitine administration. CONCLUSIONS: Vegetarians have lower plasma
      carnitine concentrations, but maintained muscle carnitine stores compared to
      omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine
      stores and slightly increases the skeletal muscle carnitine content in
      vegetarians, but without affecting muscle function and energy metabolism.

PMID- 25612931
TI  - Engagement in paid work as a protective predictor of basic activities of daily
      living disability in Japanese urban and rural community-dwelling elderly
      residents: An 8-year prospective study.
AB  - AIM: To examine whether engaging in paid work is a predictor of maintaining good
      functional health among Japanese older adults in both urban and rural
      communities. METHODS: We used the 8-year longitudinal Tokyo Metropolitan
      Institute of Gerontology Longitudinal Interdisciplinary Study on Aging with 306
      and 675 persons aged 65-84 years from Koganei City (urban) and Nangai Village
      (rural), respectively, who are independent in basic activities of daily living
      (BADL). In order to examine the declining patterns in BADL and evaluate the
      predictive value of working status for future BADL disability, we applied the log
      rank test of cumulative proportion curves and the Cox proportional hazard model
      by sex, controlling for age, research fields, years of education, marital state,
      chronic medical conditions, pain, instrumental activities of daily living (IADL),
      smoking status, exercise habits, life satisfaction, usual walking speed and serum
      albumin for evaluating the predictive value of working status at baseline for
      future BADL disability. RESULTS: In both areas, participants who were not working
      were more likely to decline in BADL than those working (P < 0.05), except for
      women in urban Koganei. Male participants who did not engage in paid work had a
      higher adjusted hazard ratio of onset of BADL disability, compared with those
      working, but this was not seen for female participants. CONCLUSIONS: Working
      might be protective from a decline in BADL only for men, but not for women.
      Regarding the difference of sex roles in conventional Japanese society, working
      would be an effective solution especially for men to participate in social
      activities.

PMID- 25612932
TI  - Forensic determination of blood sample age using a bioaffinity-based assay.
AB  - A bioaffinity-driven cascade assay was developed to determine the time elapsed
      from the point a blood sample was left at a crime scene to the point of
      discovery. Two blood markers, creatine kinase (CK) and alanine transaminase
      (ALT), were utilized to determine the age of the blood spot based on their
      natural denaturation processes. The analysis with the proposed bioassay was
      performed in human serum samples, which underwent the aging process under
      environmental conditions that could be expected at crime scenes. The
      concentration of the markers in the sample was based on physiological levels
      present in healthy adults. These two markers were concerted in a biocatalytic
      cascade composed of two parallel subsystems, with each of them following the
      activity of one marker. Both markers have very distinct denaturation rates which
      would not allow them to be used in a single marker setup while still providing
      satisfactory results. However, by parallel tunable monitoring of both markers, it
      is possible to provide information of the blood sample age with low temporal
      error for a prolonged period of time. To mimic a possible real crime scene
      situation - the reliability of the proposed assay was then successfully tested on
      dried/aged serum samples (up to 5 days old) in environments with different
      temperatures.

PMID- 25612933
TI  - Probing the anticancer-drug-binding-induced microenvironment alterations in
      subdomain IIA of human serum albumin.
AB  - The binding interaction of anticancer drug (using 5-fluorouracil (FU) as an
      example) with the model protein human serum albumin (HSA), and the FU-binding
      induced microenvironment alterations in subdomain IIA of HSA molecule were
      studied by a combination of spectroscopic techniques and molecular docking
      method. The results indicated that the nature of forces involved in binding
      interaction between HSA and FU molecule were mainly van der Waal's forces and
      hydrogen bonding interactions. These interactions resulted in the formation of FU
      HSA complex, making the local microenvironment in subdomain IIA of the protein
      more hydrophobic than its native state. Moreover, the interaction caused the
      large conformation changes of HSA, leading to the increase of the compact alpha
      helix structures at low concentration of FU (less than 150 MUM). However, the
      high concentration of FU (higher than 150 MUM) made the compact alpha-helix
      structure decreasing, probably due to the protein undergoing some sort of
      distortion. Molecular docking study revealed that FU could enter the inside a
      hydrophobic cavity of subdomain IIA (Sudlow's site I) in proximity of Trp214
      residue with the formation of specific hydrogen bonding with Trp214 and Lys199
      residues, causing the fluorescence quenching of Trp214 through a static quenching
      mechanism. The study essentially provides an effective way for investigating the
      microenvironment alterations of protein induced by the drug molecules, and this
      approach can further be used in development of biomedicines and assessment of the
      safety-engineered drug delivery.

PMID- 25612934
TI  - Dispersion-precipitation synthesis of nanosized magnetic iron oxide for efficient
      removal of arsenite in water.
AB  - Nanosized magnetic iron oxide was facilely synthesized by a dispersion
      precipitation method, which involved acetone-promoted precipitation of colloidal
      hydrous iron oxide nanoparticles and subsequent calcination of the precipitate at
      250 degrees C. Characterization by X-ray diffraction, transmission electron
      microscopy, Raman spectroscopy, nitrogen sorption, and vibrating-sample
      magnetometry revealed that the material was a composite of alpha-Fe2O3 and gamma
      Fe2O3 with primary particle size of 15-25 nm and specific surface area of 121
      m(2)/g, as well as superparamagnetic property. The material was used as adsorbent
      for the removal of arsenite in water. Batch experiments showed that the
      adsorption isotherms at pH 3.0-11.0 fit the Langmuir equation and the adsorption
      obeys pseudo-second-order kinetics. Its maximum sorption capability for arsenite
      is 46.5 mg/g at pH 7.0. Coexisting nitrate, carbonate, sulfate, chloride, and
      fluoride have no significant effect on the removal efficiency of arsenite, while
      phosphate and silicate reduce the removal efficiency to some extent. The As(III)
      removal mechanism is chemisorption through forming inner-sphere surface
      complexes. The efficiency of arsenic removal is still maintained after five
      cycles of regeneration-reuse.

PMID- 25612935
TI  - [The invisible radiologist: cause or effect?].

PMID- 25612936
TI  - Two widespread green Neottia species (Orchidaceae) show mycorrhizal preference
      for Sebacinales in various habitats and ontogenetic stages.
AB  - Plant dependence on fungal carbon (mycoheterotrophy) evolved repeatedly. In
      orchids, it is connected with a mycorrhizal shift from rhizoctonia to
      ectomycorrhizal fungi and a high natural (13)C and (15)N abundance. Some green
      relatives of mycoheterotrophic species show identical trends, but most of these
      remain unstudied, blurring our understanding of evolution to mycoheterotrophy. We
      analysed mycorrhizal associations and (13)C and (15)N biomass content in two
      green species, Neottia ovata and N. cordata (tribe Neottieae), from a genus
      comprising green and nongreen (mycoheterotrophic) species. Our study covered 41
      European sites, including different meadow and forest habitats and orchid
      developmental stages. Fungal ITS barcoding and electron microscopy showed that
      both Neottia species associated mainly with nonectomycorrhizal Sebacinales Clade
      B, a group of rhizoctonia symbionts of green orchids, regardless of the habitat
      or growth stage. Few additional rhizoctonias from Ceratobasidiaceae and
      Tulasnellaceae, and ectomycorrhizal fungi were detected. Isotope abundances did
      not detect carbon gain from the ectomycorrhizal fungi, suggesting a usual
      nutrition of rhizoctonia-associated green orchids. Considering associations of
      related partially or fully mycoheterotrophic species such as Neottia camtschatea
      or N. nidus-avis with ectomycorrhizal Sebacinales Clade A, we propose that the
      genus Neottia displays a mycorrhizal preference for Sebacinales and that the
      association with nonectomycorrhizal Sebacinales Clade B is likely ancestral. Such
      a change in preference for mycorrhizal associates differing in ecology within the
      same fungal taxon is rare among orchids. Moreover, the existence of rhizoctonia
      associated Neottia spp. challenges the shift to ectomycorrhizal fungi as an
      ancestral pre-adaptation to mycoheterotrophy in the whole Neottieae.

PMID- 25612937
TI  - Genetic variants of the DNA damage repair genes XRCC4 and RAD51 are associated
      with susceptibility to esophageal cancer.
AB  - OBJECTIVE: Altered DNA damage repair genes have been demonstrated to contribute
      to tumorigenesis. This study explored the relationship of genetic polymorphisms
      of the DNA repair genes XRCC4 and RAD51 to the risk of esophageal cancer.
      METHODOLOGY: Genotyping of XRCC4 G-1394T (rs6869366) and RAD51-G135C by PCR-RFLP
      analysis was performed on 477 participants, of whom 219 were patients with
      esophageal cancer; the remaining participants were healthy. Statistical analysis,
      including Chi(2) test and logistic regression, was used to assess genotypic
      distributions and their correlation with cancer risk. RESULTS: Carriers of the
      XRCC4 rs6869366 G allele (GT+GG) were at a significantly higher risk of
      esophageal cancer compared to individuals with the TT genotype [odds ratio
      (OR)=3.35, 95% confidence interval (CI): (1.16-10.24)]. Carriers of the C allele
      of RAD51 G135C (GC+CC) had a significantly increased risk of esophageal cancer
      compared to individuals with the GG genotype (OR=2.53, 95%CI: 1.15-6.70).
      Further, the variant genotypes of XRCC4 and RAD51 interacted to exacerbate the
      risk of esophageal cancer (OR=8.92, 95%CI: 2.47-38.20). CONCLUSIONS: Variants of
      the DNA damage repair genes XRCC4 and RAD51 increase the risk of esophageal
      cancer.

PMID- 25612938
TI  - Integrated modeling of protein-coding genes in the Manduca sexta genome using RNA
      Seq data from the biochemical model insect.
AB  - The genome sequence of Manduca sexta was recently determined using 454
      technology. Cufflinks and MAKER2 were used to establish gene models in the genome
      assembly based on the RNA-Seq data and other species' sequences. Aided by the
      extensive RNA-Seq data from 50 tissue samples at various life stages, annotators
      over the world (including the present authors) have manually confirmed and
      improved a small percentage of the models after spending months of effort. While
      such collaborative efforts are highly commendable, many of the predicted genes
      still have problems which may hamper future research on this insect species. As a
      biochemical model representing lepidopteran pests, M. sexta has been used
      extensively to study insect physiological processes for over five decades. In
      this work, we assembled Manduca datasets Cufflinks 3.0, Trinity 4.0, and Oases
      4.0 to assist the manual annotation efforts and development of Official Gene Set
      (OGS) 2.0. To further improve annotation quality, we developed methods to
      evaluate gene models in the MAKER2, Cufflinks, Oases and Trinity assemblies and
      selected the best ones to constitute MCOT 1.0 after thorough crosschecking. MCOT
      1.0 has 18,089 genes encoding 31,666 proteins: 32.8% match OGS 2.0 models
      perfectly or near perfectly, 11,747 differ considerably, and 29.5% are absent in
      OGS 2.0. Future automation of this process is anticipated to greatly reduce human
      efforts in generating comprehensive, reliable models of structural genes in other
      genome projects where extensive RNA-Seq data are available. 

PMID- 25612939
TI  - Ophthalmological assessment of cannabis-induced persisting perception disorder:
      is there a direct retinal effect?
AB  - PURPOSE: Cannabis is a psychotomimetic agent that induces impairment of sensory
      perception. We present detailed clinical and electrophysiological data of
      patients with hallucinogen persisting perception disorder (HPPD) after marijuana
      consumption. METHODS: A HPPD patient and four heavy cannabis smokers with no
      visual disturbances (controls) underwent complete ophthalmological examination
      including psychophysical tests (visual acuity, color vision, visual field, and
      dark adaptation) and detailed electrophysiological examinations, including
      extended Ganzfeld ERG, multifocal ERG, and electrooculography (EOG). Furthermore,
      electrically evoked phosphene thresholds (EPTs) were measured to further evaluate
      retinal function. RESULTS: Ophthalmological and most electrophysiological
      examinations were within normal limits for the HPPD patient and for all control
      subjects. Interestingly, EOG results of the HPPD patient showed a slightly
      reduced fast oscillation ratio, diminished standing potentials of the slow
      oscillations, and a light peak within normal range resulting in higher Arden
      ratios. The EPTs of the patient were reduced, in particular for pulses with long
      durations (50 ms) causing visual sensations even at lowest possible currents of
      the neurostimulator. The control subjects did not reveal such alterations.
      CONCLUSIONS: Our findings suggest a direct effect of cannabinoids on the retina
      and retinal pigment epithelium function, which may be involved in disturbances of
      the visual function experienced after drug consumption. The observations
      presented here may contribute to the elucidation of the detailed mechanism.
      Furthermore, EOG and EPT measurements may be useful tools to demonstrate long
      term retinal alterations in cannabis-induced HPPD in patients.

PMID- 25612942
TI  - [Allergic reaction after ingestion of pancakes].
AB  - Buckwheat is increasingly used in food and pillows in Europe and is a potent
      potential allergen when ingested or inhaled. A 74-year-old Danish woman
      experienced anaphylaxis after ingesting industrially manufactured pancakes. She
      was IgE-sensitized and was persistently asymptomatic after allergen elimination.
      A thorough medical history is pivotal to identify untraditional allergens that
      can evoke severe allergic reactions. 

PMID- 25612941
TI  - Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib
      resistant models.
AB  - Current relapse rates in acute myeloid leukemia (AML) highlight the need for new
      therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor,
      and marizomib, a second-generation proteasome inhibitor, are emerging as valuable
      therapeutic options for hematological malignancies. Here we evaluated apoptotic
      effects of this combinatorial therapy in AML models and report earlier and higher
      reactive oxygen species induction and caspase-3 activation and greater caspase-8
      dependence than with other combinations. In a bortezomib refractory setting,
      panobinostat induced high levels of DNA fragmentation, and its action was
      significantly augmented when combined with marizomib. These data support further
      study of this combination in hematological malignancies. 

PMID- 25612943
TI  - [Haemophilus influenzae type b meningitis in a vaccinated, immunocompetent infant
      with reactive arthritis].
AB  - Due to the excellent immunogenicity of the Haemophilus influenzae type b (Hib)
      conjugate vaccines, vaccine failures are rarely seen in patients following the
      recommended national immunization programmes. We present an infant with Hib
      meningitis despite relevant prophylaxis, without known risk factors such as
      medical co-morbidity, immunosuppression, immunoglobulin deficiency or
      prematurity. Later, a reactive arthritis developed. In conclusion, Hib-meningitis
      can occur in vaccinated, immunocompetent patients, and antibiotics covering Hib
      should be chosen in patients presenting with meningitis. 

PMID- 25612940
TI  - Phosphorylation of spleen tyrosine kinase at tyrosine 348 (pSyk348) may be a
      marker of advanced phase of Chronic Myeloid Leukemia (CML).
AB  - We investigated Syk as a potential marker of CML progression. We observed a
      significant over-expression of Syk mRNA and constitutive phosphorylation of Syk
      Y348 in blast cells from six AP or BP-CML, but not in 15 CML in chronic phase. We
      could follow in vivo the recurrence of pSyk(348) throughout blast cell escape,
      despite observing storage of dasatinib in blast cells. A combination of dasatinib
      and R406 did not improve therapeutic efficacy in vitro. Our results strongly
      suggest that Syk activation could be a relevant biomarker of disease progression
      and dasatinib resistance but is probably not a molecular target.

PMID- 25612944
TI  - [Varicella-zoster virus infection in a child complicated with bacterial
      pneumonia].
AB  - This case report describes how a three-year-old girl referred to our paediatric
      ward, infected with varicella-zoster virus and a bacterial pneumonia causing
      atelectasis. The girl did not respond to initial treatment with intravenous
      antibiotics. Only after a lung drain was inserted she gradually recovered. We
      briefly describe the incidence of bacterial pneumonia as a complication to
      varicella-zoster virus and raise the question whether to vaccinate against
      varicella-zoster virus. 

PMID- 25612945
TI  - [Normal D-dimer in two patients with pacemaker and deep venous thrombosis in an
      upper extremity].
AB  - Danish guidelines recommend the use of D-dimer to exclude deep venous thrombosis
      (DVT) in the lower extremities. However, guidelines are lacking for DVT in the
      upper extremities. We describe two young women with transvenous pacemaker
      electrodes and symptomatic DVT in related veins. Despite a normal D-dimer, DVT
      was verified by colour Doppler ultrasound in both cases. The guidelines of
      American College of Chest Physicians recommend initial evaluation using colour
      Doppler ultrasound as front-line examination. Accordingly, we suggest a similar
      revision of Danish guidelines incorporating upper extremity DVT as well. 

PMID- 25612946
TI  - [Pre-sacral cyst as differential diagnosis to recurrent pilonidal cyst with
      abscess].
AB  - A 31-year-old man presented with a recurrent abscess in the gluteal cleft. It was
      interpreted as a pilonidal sinus and he underwent surgery several times. The
      modified Bascom's asymmetric midgluteal cleft closure technique was used without
      satisfying clinical remission. Endoscopy, magnetic resonance imaging and
      transrectal ultrasound visualized a pre-sacral cyst, which was excised in toto
      with laterosacral approach of Kraske. A histological examination showed epidermal
      inclusion cyst. The post-operative course was uneventful. 

PMID- 25612947
TI  - [Third degree atrioventricular block in a young woman with congenital central
      hypoventilation syndrome].
AB  - Congenital central hypoventilation syndrome (CCHS) is a rare multisystem disorder
      characterized by autonomic nervous system dysfunction, which often manifests as
      failure to maintain ventilatory homeostasis during sleep. We present a case with
      a third degree atrioventricular block in a young woman with CCHS, which to our
      knowledge has not been seen before. As sudden death is known to occur among
      patients with CCHS, and it is under consideration to offer regularly monitoring
      of patients throughout childhood and adolescence. 

PMID- 25612948
TI  - [Raynaud's phenomenon of the papilla mammae caused by breastfeeding].
AB  - In Denmark, the benefits of breastfeeding are emphasized and the Danish Health
      and Medicines Authority encourages women to breastfeed for at least six months.
      Raynaud's phenomenon can occur in any small arteriole and cause painful,
      temporary ischaemia. Women quit breastfeeding prematurely for a variety of
      reasons, pain being just one of them. In this case report we describe an incident
      of Raynaud's phenomenon of the nipple and describe how correct diagnosis can
      prevent unnecessary medical treatment and cause relief of symptoms, thus avoiding
      premature cessation of breastfeeding. 

PMID- 25612949
TI  - [Common variable immunodeficiency can present as a multisystemic disorder].
AB  - Common variable immunodeficiency is the second most common primary
      immunodeficiency with a prevalence of approx. 1/10.000-50.000. The clinical
      challenge is early diagnosis and efficient supportive treatment. The purpose of
      the present article is to focus on the complexity of the disease, including the
      risk of a long pre-diagnostic period and to focus on the sarcoidosis-like variant
      and the possible impact of immunoglobulin subclass deficiency. 

PMID- 25612950
TI  - [Depression remitted after subarachnoid haemorrhage].
AB  - A 65-year-old man was seen in a specialized ambulatory for mood disorders because
      of treatment-resistant depression. He was treated throughout a period of three
      years with selective serotonin reuptake inhibitor, dual action, lithium,
      nortriptyline, reboxetine, aripiprazole, benzodiazepines, isocarboxazide and
      lamotrigine with no significant effect. However, the psychiatric symptoms
      resolved abruptly after a subarachnoid haemorrhage. The patient was turned over
      to his general practitioner 15 months after the incidence with continuously
      complete remission. 

PMID- 25612952
TI  - [Acrometastasis from breast cancer after the use of frozen gloves by adjuvant
      chemotherapy].
AB  - A woman was referred to adjuvant chemotherapy after radical mastectomy. Frozen
      gloves were used to prevent onycholysis and neurotoxicity. Because of rapid
      progression of the cancer she received palliative chemotherapy. Shortly after she
      presented with growing subungual inflammation, first suspected to be a felon, but
      later diagnosed as a metastasis. Acrometastasis is very rare and is often
      mistaken for infection. The learning point is to consider acrometastasis when
      treatment for felon fails in patients with a history of cancer. A possible
      relationship between frozen gloves and acrometastasis cannot be excluded. 

PMID- 25612951
TI  - [Fatal neutropenic enterocolitis in a patient with castration-resistant prostate
      cancer treated with first-line chemotherapy].
AB  - Neutropenic enterocolitis (NE) is a possible life-threatening complication to
      chemotherapy. The pathogenesis is multi-factorial with mucosal injury and
      impaired mucosal defence as contributing factors. Histopathological findings are
      heterogeneous. Clinical presentation includes neutropenia, fever and abdominal
      pain. Treatment is not clearly defined. We present a fatal case of NE in a
      patient with prostate cancer treated with first-line chemotherapy, docetaxel 75
      mg/m2 every three weeks and prednisolone 5 mg * 2 daily. The post-mortem
      examination confirmed NE with prostate cancer cells in bowel wall.

PMID- 25612954
TI  - [Dientamoeba fragilis infection as cause of severe abdominal discomfort and
      flatulence].
AB  - The clinical significance of Dientamoeba fragilis infection is controversial. We
      describe a case-history of a 16-year-old patient, who had suffered severe
      abdominal discomfort and flatulence through his lifetime. He was eventually
      diagnosed with D. fragilis infection, and eradication of D. fragilis with high
      dose metronidazole kept him without symptoms for one year. Recurrence of the
      symptoms and recurrence of the D. fragilis infection was thereafter treated
      successfully with paromomycin. 

PMID- 25612953
TI  - [Volar dislocation of the second and third carpometacarpal joint three months
      after a fall during a soccer game].
AB  - Volar dislocation of the second and third carpometacarpal joint is extremely rare
      and most often caused by high-energy trauma. In this case a 15-year-old boy fell
      on his hand while playing soccer. The injury was undiagnosed for three months,
      perhaps due to an ipsilateral forearm fracture. He was treated with open
      reduction and Kirchner wire fixation for nine weeks. At two years follow-up he
      had a painfree hand with a 20% reduction in grip strength. 

PMID- 25612955
TI  - [Frontal fibrosing alopecia is a variant of lichen planopilaris].
AB  - Frontal fibrosing alopecia is a scarring alopecia which typically affects the
      frontotemporal region of the scalp. Loss of hair in the other areas of the skin
      is present in the majority of cases. The condition is overrepresented among
      postmenopausal women, but men and premenopausal women can be affected as well.
      Our case is the first one described in the Danish literature. A 73-year-old woman
      had a typical presentation of the disease and responded well to treatment with
      hydroxychloroquine. We discuss clinical presentation, differential diagnosis and
      treatment modalities to this relatively newly described condition. 

PMID- 25612956
TI  - [Chronic monstrous urine retention].
AB  - A 75-year-old male was diagnosed with renal mass at a computed tomography during
      an examination for extended abdominal girth. A large mesenterical cyst was also
      detected. The patient had infrequent voiding, which he had trained over many
      years as a taxi driver. A basic physical examination led to suspect urinary
      retention. His creatinine level was normal and he had no hydronephrosis. A
      renography showed equal function, but prolonged bilateral outflow. The volume
      extracted by urethral catheter passed 15 l. Absence of hydronephrosis and normal
      S-creatinine level has not been described in chronic urinary retention of this
      extent. Hydronephrosis is seen, but in much smaller volume of retention.
      Infrequent voiding is easily diagnosed. Urinary retention should be suspected
      when finding median cystic processes.

PMID- 25612957
TI  - [Monteggia fractures in children can be overlooked].
AB  - Monteggia fractures in children are rare fractures presenting with anterior
      radial head dislocation and ulnar bowing in typical cases. In adulthood, pain,
      instability, deformity, loss of power and range of motion in the elbow joint are
      experienced. Early treatment is crucial, since the prognosis is depending on the
      time delay from injury to treatment. Full forearm X-rays including the elbow
      joint in two perpendicular projections are highly recommended in order to achieve
      an exact diagnosis without delay. 

PMID- 25612958
TI  - [Pregabalin can cause addiction and withdrawal symptoms].
AB  - A 38-year-old man was referred to the psychiatric department due to auditory
      hallucinations, suicidal ideation and a large daily intake of 8.4 g pregabalin.
      The Danish National Medication Register showed that the patient had bought
      pregabalin 21 times within the last two months, a total of 487.2 g pregabalin.
      Withdrawal symptoms disappeared within 48 hours, psychotic experiences and the
      suicidal ideations faded during the next couple of weeks. High doses of
      pregabalin are tolerated with surprisingly few toxicological consequences, though
      lethal cases have been described. Pregabalin abuse, however, can lead to
      dependency. 

PMID- 25612959
TI  - [Problematic treatment of cholecystitis in a gastric bypass patient after
      abdominoplasty].
AB  - Gastric bypass patients are at risk of late procedure-related complications, e.g.
      internal hernia or cholecystolithiasis. These complications may be important to
      identify before other surgical procedures are performed. The treatment of
      cholecystitis based on cholecystolithiasis in a patient who had recently
      undergone abdominoplasty may be highly problematic and may lead to an exacerbated
      situation. 

PMID- 25612960
TI  - [Tubercular spondylodiscitis in a young woman with thoracic backpain].
AB  - We present a case of a young woman experiencing high thoracic backpain and
      neurological symptoms of medullar compression due to spondylodiscitis from
      Mycobacterium tuberculosis. An important differential diagnosis of
      spondylodiscitis is metastatic lesions of the spine. Metastatic lesions most
      often appear in the thoracic region of the spine and high thoracic pain should be
      considered a "red flag". Both conditions often show up late on conventional
      imaging and we discuss the need for the primary sector to be able to refer
      directly to magnetic resonance imaging for quick and reliable diagnosis.

PMID- 25612961
TI  - [High doses of aldosterone antagonist is a condition of sufficient blood pressure
      control in bilateral adrenal hyperplasia].
AB  - Primary aldosteronism occurs in 1-10% of hypertensive patients and is classified
      in adenomas or bilateral adrenal hyperplasia. Computed tomography (CT) or
      magnetic resonance imaging can be used to discriminate these subtypes and in
      guiding treatment selection. This case report describes a 65-year-old man with
      hypertension and hypokalaemia during 25 years. Bilateral adrenal hyperplasia was
      diagnosed based on a CT, and an oral sodium-loading test with measurement of
      renin and aldosterone confirmed the diagnosis. Blood pressure and potassium in
      plasma was normalized during treatment with the mineralocorticoid receptor
      antagonist eplerenon. 

PMID- 25612962
TI  - [Working as a sandblaster can cause silicosis].
AB  - Silicosis is a common occupational disease worldwide. It is caused by the
      inhalation of crystalline silicon dioxide, i.e. silica. Quartz is a common form
      of silica and occurs in sandstone and granite. Occupational exposure can occur
      e.g. in mining, quarrying and sandblasting. The inhaled silica triggers an
      inflammatory response when phagocytosed which eventually causes fibrosis. We
      present a 45-year-old male Danish sandblaster who developed silicosis, and due to
      rapid decline in lung function received a lung transplant with an excellent
      result.

PMID- 25612963
TI  - [Phenotypic variability in a family with genetically verified familial hemiplegic
      migraine type 2].
AB  - After playing handball, a 13-year-old girl developed a comatose condition during
      7-10 days with hemiparesis and aphasia. From age three to nine she was treated
      for partial epilepsy. She never had symptoms of migraine. Her father had
      childhood epilepsy and at the age of 40 and 44 he experienced two attacks with
      prolonged coma, fever, seizures, hemiparesis and aphasia. His mother had symptoms
      of severe hemiplegic migraine. Father and daughter were genetically tested and an
      earlier described mutation in ATP1A2 gene was found. These cases illustrate the
      phenotypic variability in familial hemiplegic migraine type 2.

PMID- 25612964
TI  - [Renal cell carcinoma metastasis to the thyroid gland 15 years after
      nephrectomy].
AB  - Renal cell carcinoma (RCC) metastasis to the thyroid gland is rare and can mimic
      primary thyroid carcinoma leading to diagnostic difficulties. We present a case
      of a 55-year-old female with RCC metastasis to the thyroid gland 15 years after
      nephrectomy. Diagnosis was made after total thyroidectomy. This case emphasizes
      the importance of considering metastasis in patients with increasing growth of
      the thyroid gland over a short period of time known with earlier RCC, even
      decades after nephrectomy. 

PMID- 25612965
TI  - [Serious bleeding complications caused by warfarin with international normalized
      ratio 2.1].
AB  - The risk of bleeding due to anticoagulation therapy with warfarin rises
      exponentially, when the international normalized ratio (INR) exceeds 4.5. We
      present a 52-year-old male admitted to the hospital with severe bleeding in the
      lower limbs caused by warfarin. Laboratory tests showed therapeutic INR (2.1),
      however the activated partial tromboplastin time was unusually prolonged (135
      sec.) and a severe, reversible reduction in factor IX was detected. These
      findings were suggestive of a mutation in the factor IX propeptide, but
      thrombocytopathy induced by selective serotonin re-uptake inhibitors could have
      worsened the bleeding. 

PMID- 25612966
TI  - [Cancer can be a differential diagnosis by psychiatric symptoms].
AB  - We present a patient with psychiatric symptoms as the first manifestation from an
      undetected brain tumor. The patient had symptoms of psychosis and a prior history
      with depression. A slight alteration in consciousness was found but no
      neurological deficits. Blood tests showed increased infection counts and
      particularly increased creatinine kinase. A large frontal glioma cerebri was
      found on cranial computed tomography and was surgically removed. The symptoms
      fully resolved afterwards. Psychosis can present with a variety of symptoms but
      particularly altered consciousness should arouse suspicion of physical origin. 

PMID- 25612967
TI  - [Avulsion fracture of the serratus anterior muscle in a golfer].
AB  - Golf is a sport with much repetitive actions often causing overuse injuries. We
      report a case of a left side avulsion fracture of the anterior serratus at the
      insertion on costa 4-6. A professionel golfer experienced sudden onset of pain of
      the chest during a golfswing. Clinically the patient had winging of the scapula
      and pain at the lateral side of costa 4-6. Ultrasonography showed an avulsion
      fracture of costa 5 at the insertion of the anterior serratus. The patient was
      referred to scapula-stabilising rehabilitation and fully recovered.

PMID- 25612968
TI  - [Bilateral hypothenar hammer syndrome].
AB  - Hypothenar hammer syndrome is caused by ulnar artery occlusion subsequent to
      repeated blunt trauma such as by using the hypothenar as a hammer during work.
      Allen's test permits the detection of this frequent and often overlooked cause of
      hand pain and ischaemia. The four bilateral hypothenar hammer syndromes described
      in this case report occurred after several years of occupational exposure to hard
      shocks/impacts to the hypothenar from workpieces, which were held with a firm
      grip. 

PMID- 25612969
TI  - [Lithium can be given to patients on haemodialysis treatment].
AB  - Lithium-induced nephropathy is a known complication of lithium treatment in
      bipolar disorder. Treatment with lithium should be discontinued, if there is
      evidence of lithium-induced nephropathy. However, lithium can be given to
      patients with end-stage-renal-disease on haemodialysis treatment, if there is no
      other way to control the bipolar disorder. We report one patient who was
      successfully treated with lithium in parallel with haemodialysis. 

PMID- 25612970
TI  - [Third degree atrioventricular block treated without pacemaker].
AB  - A 53-year-old male was admitted due to an asymptomatic third degree
      atrioventricular (AV) block of proximal type (QRS duration below 0,12 sec.). With
      telemetry a normal heart rate was observed and a stress test showed a maximum
      heart rate of 101% of the expected. Blood samples and stress echo-cardiography
      showed normal values. Permanent pacemaker (PM) placement was rejected and the
      patient was followed in the outpatient clinic. PM implantation carries a risk of
      complications but without it the condition can progress. Treatment of
      asymptomatic third degree AV-block is debated and not entirely clear. 

PMID- 25612971
TI  - [Splenic injury after sigmoidoscopy].
AB  - Endoscopy of colon and rectum is a commonly used diagnostic and therapeutic
      procedure, which is generally safe although complications such as bleeding and
      perforation occur. There is, however, a small risk of splenic injury with
      potentially lethal outcome. We describe a case of splenic injury after
      sigmoidoscopy in a 48-year-old male. 

PMID- 25612972
TI  - [Uterine rupture without preexisting caesarean section after perforation of the
      uterus during evacuation].
AB  - Uterine rupture is a serious complication, associated with perinatal and maternal
      morbidity and mortality. This case report describes uterine rupture in a patient
      who did not have any previous caesarean section. The patient had acute abdominal
      pain, hypertonic uterus, blood in the amniotic fluid and abnormal
      cardiotocographic values. An abruption of the placenta was suspected, and an
      acute caesarean section was performed during which a rupture in fundus uteri was
      found. It was later experienced that the patient ten years earlier had suffered a
      uterine perforation during evacuation after a late abortion. 

PMID- 25612973
TI  - [Buschke-Ollendorff syndrome in two generations imitated Calve-Legg-Perthes
      disease].
AB  - Buschke-Ollendorff syndrome is a rare condition characterized by skin
      manifestations and osteopoikilosis. We describe a mother and her son who
      presented with indurated skin lesions suggestive of connective tissue naevi. X
      rays showed multiple symmetrical foci of osteosclerosis. They had both been
      diagnosed earlier with Calve-Legg-Perthes disease, which on revision most likely
      represented Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome may imitate
      Calve-Legg-Perthes disease. Skin signs may be the clue to diagnosis. Main
      differentials are sclerotic bone metastases and osteoma. 

PMID- 25612974
TI  - [Compartment syndrome of the foot].
AB  - Compartment syndrome of the foot is a rare but nevertheless a very important limb
      threatening condition which is generally caused by traumatic injuries. Diagnosis
      is made by recognising the common signs and symptoms: pain out of proportion,
      pain with passive stretch of the compartment, paraesthesias, and in worst case,
      paresis and missing pulse. Elevated pressure in one or several of the nine
      compartments in the foot confirms the diagnosis. When suspecting compartment
      syndrome acute fasciotomi is essential in order to prevent devastating
      complications such as nerve dysfunctions and foot deformities.

PMID- 25612975
TI  - [Partial Achilles tendon ruptures exist].
AB  - In this case report a typical case with partial Achilles tendon rupture is
      described. Because of unspecific symptoms, near normal MRI and no clinical signs
      of total rupture the diagnosis was delayed for almost four months. Open surgery
      showed a partial Achilles tendon rupture without significant signs of
      tendinopathy. The tendon was sutured and the post-operative period was
      uneventful. 

PMID- 25612976
TI  - [Pneumomediastinum and airway obstruction after traumatic rib fractures].
AB  - We present a case of upper airway obstruction not previously reported in
      combination with traumatic rib fractures, pneumothorax, pneumomediastinum and
      subcutaneous emphysema. A 95-year-old female presented with swelling of the face,
      neck and upper body. Stridor indicated upper airway obstruction and intubation
      was performed. A computed tomography revealed subcutaneous emphysema, pneumo
      thorax, pneumomediastinum and rib fractures. Bilateral chest tubes were placed
      and the patient was admitted to intensive care. Upper airway obstruction should
      be considered in patients with chest trauma. 

PMID- 25612977
TI  - [Eating disorder in a nineteen months-old girl and associated mother child
      relationship disturbance].
AB  - Feeding and eating problems and weight faltering are common causes for parents
      contact to health services in infancy and early childhood, and 0.15% of the child
      population aged 0-3 years are diagnosed at hospital with an ICD-10 childhood
      eating disorder. We describe the clinical presentation of an early feeding and
      eating disorder in a child of basically normal health and development. The case
      illustrates the significance of the mother child relationship both in the
      putative risk mechanisms and as a key factor in the treatment. The importance of
      a close cooperation between paediatric and child psychiatric services in these
      patients is underscored.

PMID- 25612978
TI  - [Severe recurrent carbon monoxide poisoning caused by smoking].
AB  - Carbon monoxide (CO) is an odourless, colourless and toxic gas. Sources of CO
      include car exhaust, charcoal and tobacco smoke. CO binds to haemoglobin forming
      carboxyhaemoglobin (COHb). Heavy smokers have COHb levels up to 15%. There are
      reports of COHb levels of 24,2% caused by tobacco use and 28,7% after narghile
      smoking. A 54-year-old woman with schizophrenia was admitted at the intensive
      care unit with COHb levels as high as 35% caused by cigarillo smoking. She also
      presented with severe thiazide-induced hyponatriaemia and high haemoglobin
      levels. 

PMID- 25612979
TI  - [A rare case of Horner's syndrome in pituitary apoplexy].
AB  - Pituitary apoplexy is a rare but potentially life-threatening condition that is
      classically comprised of acute-onset severe headache accompanied by nausea and
      vomiting, visual field disturbances, external ophthalmoplegia, and often
      hypopituitarism. A case illustrating the highly variable clinical appearance of
      this condition is presented. 

PMID- 25612980
TI  - [High-risk pregnancy in a woman with Marfan syndrome, a bicuspid aortic valve,
      and a dilated aortic sinus].
AB  - A 29-year-old woman with Marfan syndrome, a bicuspid aortic valve, and a dilated
      aortic sinus (5.2 cm) presented herself in clinic 14 weeks pregnant. She was
      advised to discontinue the pregnancy due to risk of dissection; however, she
      decided to continue. She was treated with labetalol (300 mg/day) to reduce blood
      pressure and was admitted for bed rest from week 30. Her aortic diameter was
      assessed by echocardiography every 2nd week and remained unchanged. She was
      treated with betamethason at week 26 and the child was born by a caesarean
      section in week 35. The post-operative course was uneventful. 

PMID- 25612981
TI  - [Ischaemic colitis after loperamide treatment].
AB  - Ischaemic colitis is a potentially mortal illness which usually arises from
      decreased mesenteric blood flow. Loperamide is used in the treatment of both
      acute and chronic diarrhoea. We present a case of a 62-year-old man with no
      history of abdominal illness who was admitted with a distended and sore abdomen.
      Ten days prior to admission he was treated with loperamide. Because of his severe
      condition he had an emergency laparotomy which showed a necrotic colon and
      terminal ileum - both were resected. No thromboembolic cause was found and we
      therefore suggest loperamide as an inducing factor.

PMID- 25612982
TI  - [Clinical differentiation between intestinal tuberculosis and morbus Crohn].
AB  - We describe a case of intestinal tuberculosis in a 34-year-old Indonesian woman.
      She presented with diarrhoea, weight loss, fever and night sweat over a period of
      weeks. She underwent colonoscopy which showed a major cobblestone pattern like
      necrosis in part of the colon. An MR scan showed oedema involving the small
      intestine near the ileocoecal area and abdominal lymphadenopathy. Because of the
      patient history of recent TB exposure, ethnicity and positive T-SPOT-TB, she was
      given a course of four-drug tuberculosis treatment and responded quickly. Later
      on Mycobacterium tuberculosis was found in faeces culture. 

PMID- 25612983
TI  - [Magnetic resonance imaging as supplement to clinical examination by suspicion of
      haematocolpos].
AB  - Haematocolpos is a rare condition in young women that could be caused by
      imperforated hymen, vaginal atresia and vaginal agenesis. Haematocolpos is
      usually diagnosed at early puberty with unspecified abdominal pain and
      amenorrhoea. Three cases are presented. In one case the radiological examination
      showed incidentally a urogenital congenital anomaly known as Herlyn-Werner
      Wunderlich syndrome. A gynaecological examination should be performed to confirm
      the presence of imperforated hymen, but in cases in which other pathology is
      suspected ultrasound and MRI should also be performed. 

PMID- 25612985
TI  - [Sudden visual loss after long-lasting spinal surgery].
AB  - Visual loss after anaesthesia and surgery is a rare, unexpected and devastating
      complication which particularly occurs after long-lasting spinal and cardiac
      surgery. There are several suggested risk factors but most of them are
      unsupported. Usually both eyes are involved and there is a painless profound loss
      of vision. The pupils are not reacting to light and at the beginning normal
      fundoscopy is found. The prognosis is very bad and no documented treatment is
      known. In this case report a 61-year-old man experienced complete loss of vision
      after complicated spinal surgery. 

PMID- 25612984
TI  - [Follow-up after non-typhoidal Salmonella bacteraemia is important due to risk of
      endovascular infection].
AB  - An 81-year-old male with atherosclerosis had an episode of bacteraemia with
      Salmonella dublin six weeks prior to admission to hospital. He presented with
      confusion, fever and abdominal pain. Blood cultures revealed S. dublin, and an
      18F-fluor deoxyglucose positron emission tomography/computed tomography showed
      aortitis. Ceftriaxon and ciprofloxacin was administered. The patient was not a
      candidate for surgery and two weeks later he died from multiple organ failure.
      Follow-up visits with blood cultures after the first bacteraemia episode might
      have allowed for earlier diagnosis of the relapse. 

PMID- 25612986
TI  - [Unusually late debut of lymphangioleiomyomatosis].
AB  - The rare, severe lung disease lymphangioleiomyomatosis (LAM) usually presents
      with dyspnoea on exertion, cough and expectoration in females in the third decade
      and is worsened by pregnancy or hormone therapy. Lung transplant is often needed
      within ten years since no specific treatment is available. The patient in this
      case report was a mother of two, who had never received hormone therapy. Once,
      when she was 47-years-old, she had had a period of dyspnoea and pleural empyema
      and no diagnosis was made, but being 75-years-old she was admitted with moderate
      dyspnoea on exertion, and high resolution CT showed cysts of the lungs classical
      for LAM. 

PMID- 25612987
TI  - [Retrograde jejunal intussusception after gastric bypass].
AB  - The preferred technique in Denmark for surgical intervention for morbid obesity
      is laparoscopic Roux-en-Y gastric bypass. A rare complication to gastric bypass
      is intussusception of the small intestines. However, this diagnosis is difficult
      to determine clinically and an acute computed tomography is often necessary. We
      present the first case of retrograde jejunal intussusception after gastric bypass
      in Scandinavia. 

PMID- 25612988
TI  - [Retroperitoneal haematoma as a complication at the beginning of a laparoscopic
      operation].
AB  - After laparoscopic appendectomy complications and injury to the intraabdominal
      organs and major vessels are rare but well documented. The majority of
      complications occur during establishment of pneumoperitoneum. Frequently used
      entries are open trocar (Hasson), closed using Veress needle and direct trocar
      insertion. In this case we describe an incident where the towel clip, used to get
      hold of the supraumbilical fascia to minimize the risk of injury, was pressed
      down too hard. The retroperitoneum was accidentally punctured and a haematoma
      above vena cava was created. 

PMID- 25612989
TI  - [Transurethral prostate resection prior to kidney transplantation leading to
      urethral cicatricial tissue].
AB  - In Denmark, kidney transplantations in patients above 50 years have increased
      during the last decade. Consequently, the number of patients with lower urinary
      tract symptoms due to prostate hypertrophy increases accordingly. We describe two
      patients, who both had a resection of the prostate while having anuria and
      waiting for a kidney transplantation from a deceased donor. In both cases it was
      impossible to place a urethral catheter during the following transplantation due
      to total urethral occlusion, so a suprapubic catheter was inserted until the scar
      tissue was dilated or resected by a later transurethral intervention. 

PMID- 25612990
TI  - [Ultrasound-guided performance of labour epidural analgesia in a patient with
      thoracolumbar scoliosis].
AB  - Providing epidural analgesia in patients with scoliosis may be challenging. We
      describe ultrasound-guided insertion of an epidural catheter for labour analgesia
      and a following caesarean section in a patient with a thoracolumbar scoliosis. A
      well-functioning epidural catheter was easily inserted on the first attempt
      without any need for redirections of the epidural needle. Use of ultrasound
      imaging to guide epidural needle insertion site and trajectory can be a valuable
      tool in managing patients with scoliosis. 

PMID- 25612991
TI  - [Seminal vesicle cyst with ipsilateral renal agenesis].
AB  - A formerly healthy 41-year-old male with monosymptomatic swelling of his left
      testicle was diagnosed with testicular cancer (seminoma). During staging of the
      cancer a computed tomography showed left renal agenesis and an 8 x 6 cm
      retrovesical space-occupying lesion in the left side of the pelvis. The lesion
      was interpreted as a group of enlarged lymph nodes, but PET/CT and MRI later
      demonstrated that it was a left seminal vesicle cyst. An association between
      congenital seminal vesicle cysts and ipsilateral renal agenesis is rare and can
      be explained by their common embryologic origin. 

PMID- 25612992
TI  - [In-utero treatment of hypoplastic left heart syndrome].
AB  - In-utero treatment of fetal aortic stenosis (AS) may prevent hypoplastic left
      heart syndrome. A girl was diagnosed prenatally with severe AS and was referred
      to the Women's and Children's Hospital in Linz, Austria, where she underwent an
      intrauterine valvuloplasty of the aortic valve. Postnatally, the girl was given
      prostaglandin and operated a.m. Ross-Konno. An echocardiography at the age of
      four months showed a neoaorta without stenosis and insufficiency and a normal
      systolic function of the left ventricle. This treatment must be carefully
      considered when dealing with fetuses with AS.

PMID- 25612993
TI  - [Ipilimumab treatment of metastatic melanoma].
AB  - Until recently metastatic melanoma was a disease with limited treatment options
      and a poor prognosis. However, new promising products have been developed.
      Ipilimumab, a full human anti-cytotoxic T-lymphocyte antigen-4 antibody, has
      shown improved survival in several clinical trials and is now a part of the
      standard treatment options for this disease in Denmark. In this case report we
      present a 78-year-old man with metastatic melanoma who had complete remission
      after treatment with ipilimumab. 

PMID- 25612994
TI  - [Ischaemic colitis secondary to emphysematous pyelonephritis].
AB  - Emphysematous pyelonephritis is an acute severe necrotizing infection of the
      renal parenchyma and its surrounding tissues and up to 95% of the patients have
      diabetes. We describe a concurrent manifestation of emphysematous pyelonephritis
      and ischaemic colitis in a 51-year-old diabetic woman and conclude that the
      colitis was due to pressure from a large retroperitoneal mass and sepsis
      complications combined with underlying peripheral vascular disease because of
      diabetes mellitus and hypertension. 

PMID- 25612995
TI  - [Life-threatening extrauterine pregnancy after in vitro fertilization and
      bilateral salpingectomy].
AB  - A woman with a history of bilateral salpingectomy achieved pregnancy after in
      vitro fertilization. At the gestational age of six weeks she experienced fatigue,
      haematemesis and abdominal pain. She was hospitalized on suspicion of a peptic
      ulcer. Several physicians rejected the possibility of an ectopic pregnancy due to
      the history of salpingectomy. The patient had intraabdominal bleeding and went
      through emergency surgery because of a ruptured interstitial pregnancy. The
      purpose of this case report is to recall the risk of interstitial pregnancy in
      pregnant women with a history of salpingectomy. 

PMID- 25612996
TI  - [Secondary neoplasms of the larynx from a colonic adenocarcinoma].
AB  - Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all
      laryngeal tumours. Cutaneous melanomas are the preponderant primaries
      metastasizing to the larynx, followed by renal cell carcinomas, breast and lung
      carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely rare.
      Tumours spreading to the larynx may be asymptomatic or may result in hoarseness,
      stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma
      to the larynx usually present with disseminated disease. We present a case of an
      isolated laryngeal metastasis from a colonic adenocarcinoma. The patient was
      treated with endoscopic surgery and radiation.

PMID- 25612997
TI  - [Penetrating injury of lower extremity caused by a heavy machine gun cartridge
      casing].
AB  - Penetrating injuries caused by cartridge casing are rarely described in the
      literature. This case report presents a 21-year-old male soldier with a lower
      extremity injury caused by a heavy machine gun cartridge casing. Physical
      examination revealed an entrance wound proximal and anterior of his right thigh
      and there were no exit wound identified. A radiograph of the femur showed the
      cartridge casing to have travelled caudally into the posterior aspect of the
      knee. There were no associated fractures or neurovascular injuries. The patient
      underwent surgical wound debridement and removal of the foreign body and was
      discharged fully recovered after three days. 

PMID- 25612998
TI  - [Perinatal invasive infection with Group A Streptococci prior to rupture of the
      membranes].
AB  - We describe a case of invasive Group A Streptococci infection prior to rupture of
      the membranes in a 27-year-old woman in her 34th week of pregnancy. The patient's
      initial symptoms were flu-like with episodes of diarrhoea. After three days she
      got a fever and was committed to the obstetric ward. After 14 hours of
      observation she developed abdominal pain with palpatory soreness of the uterus.
      An acute cesarean section was performed. Group A Streptococci were found in the
      specimens from the amniotic fluid and placenta. 

PMID- 25612999
TI  - [Penile metastasis from rectum cancer primarily interpreted as Peyronie's
      disease].
AB  - We report an unusual case of penile metastasis derived from a rectal
      adenocarcinoma, which was first interpreted as Peyronie's disease. The patient
      had a single palpable mass in the penile shaft within the corpus cavernosum, with
      no ulceration or pain in the area. Two years earlier he had been treated for
      rectal cancer with neoadjuvant radiation therapy and abdomino-perineal resection.
      The mass in the penis later turned out to be a manifestation of widespread
      metastatic disease. The patient lived three years after discovery of metachronous
      metastases in penis and lungs. 

PMID- 25613000
TI  - [Renal oncocytosis is a diagnostic challenge].
AB  - Renal oncocytosis is a rare variant of renal oncocytoma with multiple, often
      bilateral oncocytomas. This case report discusses radiological and pathological
      aspects of renal oncocytoma and oncocytosis.

PMID- 25613001
TI  - [Acute myocardial infarction with fatal outcome in a 22-year-old woman].
AB  - It is important to recognize that patients with chest pain and a family history
      of cardiac diseases along with obvious risk factors might suffer from acute
      myocardial infarction. Even young females can be affected. We present a history
      of a 22-year-old woman who was predisposed to cardiac atherosclerosis. Her father
      and her brother had atherosclerotic changes in coronary arteries. Her BMI was 35
      kg/m2 and she was a smoker. Her young age misled the physicians to conclude, with
      fatal consequence, that her symptoms with chest pain and heavy feeling in both
      arms were explained by spasms of the cardia. 

PMID- 25613002
TI  - [Amyloidosis is a rare cause of heart failure].
AB  - Light-chain amyloidosis (AL) is the most common form of systemic amyloidosis and
      is associated with an underlying plasma cell dyscrasia. The disease is often
      difficult to recognize because of its broad range of manifestations and often
      vague symptoms. The clinical symptoms include proteinuria, hepatomegaly, heart
      failure and autonomic or sensory neuropathy. A 70-year-old man with a past
      medical history of sacroidosis and heart failure was admitted to hospital. He had
      breathlessness and swelling of his lower extremities. Among other symptoms the
      combination of transthoracic echo-cardiogram findings and low voltage on the ECG
      led to the diagnosis AL. 

PMID- 25613003
TI  - Update in salivary gland cytopathology: Recent molecular advances and diagnostic
      applications.
AB  - Salivary gland tumors (SGT) are notorious for their extraordinary diversity and
      for the morphological overlap that exists between many of these entities. Fine
      needle aspiration biopsy (FNAB) has a well-established role in the evaluation of
      patients with a salivary gland lesion, helping to guide clinical management.
      However, salivary gland FNAB has several limitations and does not allow for a
      specific diagnosis in some cases. For these reasons, salivary gland FNAB is
      considered one of the most challenging areas in cytopathology. Over the last
      decade, new salivary gland entities have been recognized, enlarging SGT diversity
      and complexity even more. In addition, a subset of SGT, including common entities
      such as pleomorphic adenoma and uncommon new entities such as mammary analog
      secretory carcinoma, have been characterized cytogenetically by the presence of
      specific translocations. The molecular consequences of these translocations and
      their potential prognostic and therapeutic values are not yet well characterized.
      However, these translocations and their resulting fusion oncogenes and
      oncoproteins can be used as diagnostic clues in salivary gland FNAB material in
      order to overcome the limitations of cytomorphological evaluation alone. In this
      review, we focus on SGTs currently known to harbor translocations and fusion
      genes, including uncommon and recently recognized entities, and discuss their
      potential application to salivary gland FNAB. 

PMID- 25613004
TI  - Comment on the article by Dutra Medeiros et al. entitled 'dexamethasone
      intravitreal implant for treatment of patients with persistent diabetic macular
      edema'.

PMID- 25613005
TI  - Do we need "biology-based" models to describe cell survival curves after exposure
      to ionizing radiation?

PMID- 25613006
TI  - Novel pullulan bioconjugate for selective breast cancer bone metastases
      treatment.
AB  - A novel polysaccharide bioconjugate was designed to selectively target breast
      cancer bone metastases using a bisphosphonate moiety (alendronate, ALN).
      Paclitaxel (PTX) was first covalently conjugated to pullulan (Pull) through a
      Cathepsin K-sensitive tetrapeptide spacer followed by a self-immolative
      aminobenzyl alcohol spacer to obtain Pull-(GGPNle-phi-PTX). ALN was then
      conjugated to the polymeric backbone of Pull-(GGPNle-phi-PTX) via a PEG spacer.
      The final bioconjugate Pull-(GGPNle-phi-PTX)-(PEG-ALN) was found to assemble into
      colloidal spherical structures, which were physically and chemically stable under
      physiological conditions. In vitro studies showed that Pull-(GGPNle-phi-PTX)-(PEG
      ALN) had strong affinity for hydroxyapatite, which simulates the bone tissue.
      Paclitaxel was rapidly released from the bioconjugate by Cathepsin K cleavage
      under pathological conditions. All studies performed using human MDA-MB-231-BM
      (bone metastases-originated clone), murine 4T1 breast cancer cells, murine K7M2,
      and human SAOS-2 osteosarcoma cells showed that the bioconjugate exerted an
      enhanced antiproliferative activity compared to the conjugate without the ALN.
      Furthermore, the nanoconjugate inhibited the migration of cancer cells and
      further displayed potent anti-angiogenic activity. In conclusion, the results
      showed that this conjugate has an excellent potential for selective treatment of
      bone neoplasms such as breast cancer bone metastases and osteosarcoma. 

PMID- 25613007
TI  - Evaluating the psychometric properties of an e-based version of the 39-item
      Parkinson's Disease Questionnaire.
AB  - BACKGROUND: The 39-item Parkinson's Disease Questionnaire (PDQ-39) is the most
      thoroughly validated and extensively used self-report measure for the assessment
      of health-related quality of life in people with Parkinson's (PwP). Given the
      extent of its use and increasing emphasis on electronic data capture, an e-based
      version of the PDQ-39, the ePDQ, has recently been developed. The aim of this
      short report is to present some key reliability and validity data that confirm
      the psychometric quality of the ePDQ. FINDINGS: Participants were emailed a
      unique link to an online survey incorporating the ePDQ and demographic questions.
      A total of 118 PwP fully completed the survey. Floor and ceiling effects were
      calculated to ensure responses were not biased to extreme values. Consequently,
      score reliability was assessed by item-total correlations with a range from 0.34
      to 0.90. Cronbach's alpha was calculated at between 0.64 and 0.95 for the eight
      domains of the ePDQ. Construct validity was assessed by comparing domain scores
      in relation to disease duration and gender, with hypothesised differences being
      largely confirmed. Construct validity was further assessed following a higher
      order factor analysis which confirmed the appropriateness of calculating a
      summary index score. Subsequently, significant, but moderate correlations were
      calculated between the ePDQ summary index score and disease duration and age at
      diagnosis. CONCLUSIONS: Results indicate that the ePDQ largely mirrors the
      properties of its parent instrument, the PDQ-39, in terms of reliability and
      validity. Potential users can therefore incorporate the ePDQ into computer-based
      data capture systems with confidence.

PMID- 25613008
TI  - Sendai virus particle production: a more detailed role of F and HN through,
      namely, their association with M.
AB  - The Paramyxovirus membrane associated proteins are composed of two integral
      membrane glycoproteins, HN (H, G) and F, and of a matrix protein (M) carpeting
      the membrane inner layer. For Sendai virus (SeV), F and M have been proposed to
      form a complex at the endoplasmic reticulum that further migrates to the cell
      periphery where it represents a nucleation site for viral assembly completion
      (Essaidi-Laziosi et al., 2013). HN is recruited in the assembly complex once
      expressed at the cell surface. In contrast to F and M, HN appears dispensable for
      virus particle production. However, upon F suppression, concomitant HN
      suppression restricts viral particle production much more severely than F
      suppression alone, suggesting that HN plays a role as well. In this study, we
      demonstrate that the transmembrane and cytoplasmic regions of F are sufficient to
      promote virus particle production and incorporation of a foreign protein in viral
      particles. We further identify in the F cytoplasmic tail the site of interaction
      with M. We next confirm HN participation in viral particle production and we
      provide genetic evidence for a participation of M in the process. We finally
      derive observations that may provide a mechanism by which the viral C protein
      participates in viral particle production by mediating HN-M interaction. 

PMID- 25613009
TI  - Identification of morphological differences between avian influenza A viruses
      grown in chicken and duck cells.
AB  - Although wild ducks are considered to be the major reservoirs for most influenza
      A virus subtypes, they are typically resistant to the effects of the infection.
      In contrast, certain influenza viruses may be highly pathogenic in other avian
      hosts such as chickens and turkeys, causing severe illness and death. Following
      in vitro infection of chicken and duck embryo fibroblasts (CEF and DEF) with low
      pathogenic avian influenza (LPAI) viruses, duck cells die more rapidly and
      produce fewer infectious virions than chicken cells. In the current study, the
      morphology of viruses produced from CEF and DEF cells infected with low
      pathogenic avian H2N3 was examined. Transmission electron microscopy showed that
      viruses budding from duck cells were elongated, while chicken cells produced
      mostly spherical virions; similar differences were observed in viral
      supernatants. Sequencing of the influenza genome of chicken- and duck-derived
      H2N3 LPAI revealed no differences, implicating host cell determinants as
      responsible for differences in virus morphology. Both DEF and CEF cells produced
      filamentous virions of equine H3N8 (where virus morphology is determined by the
      matrix gene). DEF cells produced filamentous or short filament virions of equine
      H3N8 and avian H2N3, respectively, even after actin disruption with cytochalasin
      D. These findings suggest that cellular factors other than actin are responsible
      for the formation of filamentous virions in DEF cells. The formation of elongated
      virions in duck cells may account for the reduced number of infectious virions
      produced and could have implications for virus transmission or maintenance in the
      reservoir host. 

PMID- 25613010
TI  - Two-dimensional covalent organic frameworks for carbon dioxide capture through
      channel-wall functionalization.
AB  - Ordered open channels found in two-dimensional covalent organic frameworks (2D
      COFs) could enable them to adsorb carbon dioxide. However, the frameworks' dense
      layer architecture results in low porosity that has thus far restricted their
      potential for carbon dioxide adsorption. Here we report a strategy for converting
      a conventional 2D COF into an outstanding platform for carbon dioxide capture
      through channel-wall functionalization. The dense layer structure enables the
      dense integration of functional groups on the channel walls, creating a new
      version of COFs with high capacity, reusability, selectivity, and separation
      productivity for flue gas. These results suggest that channel-wall functional
      engineering could be a facile and powerful strategy to develop 2D COFs for high
      performance gas storage and separation. 

PMID- 25613011
TI  - Functioning of peripheral Ia pathways in leg muscles of newly walking toddlers.
AB  - Monosynaptic and polysynaptic spinal level reflexes in the leg muscles of infants
      show significant dispersion across muscles, high variability, and no change in
      response patterns over the first 10 months. Here we tested the hypothesized
      relation between early walking experience and the tuning of these responses in
      three primary gait muscles of participants in four subgroups: cruisers (n=7) and
      toddlers with one (n=5), two (n=5), or three (n=5) months of walking experience.
      Reflex responses in multiple Ia pathways - tendon reflex (T-reflex), vibration
      induced inhibition of the T-reflex (VIM-T-reflex), and tonic vibration-induced
      reflex (VIR), were elicited by mechanical stimuli applied to the distal tendons
      of the quadriceps, gastrocnemius-soleus, and tibialis anterior of both legs.
      Walking skill was assessed via a GAITRite mat. Generally, walking experience
      seemed to be related to slowly emerging improvements and, depending on muscle
      tested and pathway, progress was quite varied. Amplitude and latency of reflex
      responses were more clearly impacted by age or leg length while the ratio or
      distribution pattern of reflex response among antagonist pairs of muscles was
      impacted by walking experience and skill. As walking experience increased, the
      ratio of reflex responses tended to increase for the stimulated and decrease for
      the antagonist reflex loops with distribution of the pattern shifting gradually
      toward a single type of reflex response in all tested muscles. The very slow
      tuning of these reflexes may underlie the many missteps and falls reported to
      occur during early walking and suggest that subsequent studies should continue to
      follow the developmental trajectory through the first year of walking experience.

PMID- 25613012
TI  - Natural History of Parkinson's Disease in the Province of Segovia: Disability in
      a 20 Years Longitudinal Study.
AB  - BACKGROUND: Parkinson's disease mainly affects the elderly population causing a
      progressive functional disability with motor, psychic, and cognitive
      deterioration. OBJECTIVE: This study was carried out to evaluate disability
      caused by Parkinson's disease by analyzing the median time to reach Hoehn and
      Yahr stage III and to investigate predictor variables based on a 20-year
      longitudinal follow-up study. METHODS: We examined 273 patients with Parkinson's
      disease recruited between 1978 and 1998. We performed a survival analysis using
      the Kaplan-Meier method to determine the time to disability and we used a Cox
      regression model to adjust prognosis factors. RESULTS: The median time to reach
      Hoehn and Yahr stage III was 7.73 years (95% CI: 5.95-8.05). Independent
      predictors of disability were: age at onset, the hazard ratio (HR) = 1.10, 95%
      CI: 1.08-1.12; UPDRS II (activities of daily living) HR = 1.08, 95% CI: 1.03
      1.14; and akinesia and rigidity at onset HR = 1.55, 95% CI: 1.07-2.24.
      CONCLUSIONS: Patients with Parkinson's disease evolve gradually toward
      disability, and prognostic factors of this evolution were identified.

PMID- 25613013
TI  - Development and validation of a liquid chromatography-tandem mass spectroscopy
      method for simultaneous determination of (+)-(13aS)-deoxytylophorinine and its
      pharmacologically active 3-O-desmethyl metabolite in rat plasma.
AB  - CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to
      phenanthroindolizidine alkaloids. A sensitive and reliable liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of CAT
      and its pharmacologically active 3-O-desmethyl metabolite (S-4) was developed and
      validated in rat plasma using rotundine as the internal standard (IS). CAT, S-4
      and IS were extracted by acetonitrile protein precipitation and separated on an
      Eclipse XDB-C18 column (1.8 MUm, 4.6 mm * 50 mm) with acetonitrile-water (27:73,
      v/v) mobile phase containing 0.1% formic acid at a 0.4 mL/min flow rate. Positive
      ion electrospray ionization in multiple reaction monitoring mode was employed to
      measure CAT, S-4 and IS by monitoring the transitions m/z 364.2->70.1 for CAT,
      350.1->70.1 for S-4 and 356.2->192.2 for IS. Good linear correlation (r(2)>0.991)
      was achieved for CAT and S-4 over the range of 0.214-128.16 and 0.044-11.00
      ng/mL, respectively. The lower limit of quantification was 0.214 ng/mL for CAT
      and 0.044 ng/mL for S-4, using 50 MUL rat plasma samples. The intra- and inter
      day precisions were not exceed 15% and the accuracy ranged between 94.80% and
      108.22%. The average extraction recoveries of both analytes were greater than
      94.62%. The method was successfully applied to the pharmacokinetic study of CAT
      and S-4 in rats after oral administration.

PMID- 25613014
TI  - Migraine and the vascular system: much has been learned but still a long way to
      go.

PMID- 25613017
TI  - Furosemide with saline hydration for prevention of contrast-induced nephropathy
      in patients undergoing coronary angiography: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: The clinical efficacy of furosemide administration in preventing
      contrast-induced nephropathy (CIN) remains uncertain. This meta-analysis was
      designed to update data on the incidence of CIN with additional furosemide
      treatment beyond saline hydration in comparison with hydration alone in patients
      undergoing percutaneous coronary intervention (PCI). MATERIAL/METHODS: A
      computerized literature search of MEDLINE, EMBASE, and Cochrane databases was
      performed. Trials were eligible if they enrolled patients undergoing coronary
      angiography and randomly allocated participants to receive furosemide
      administration in addition to saline hydration or saline hydration alone. We
      calculated odds ratios (ORs) and 95% confidence intervals (CIs) for combinations
      of studies. RESULTS: Five trials involving 1294 patients (640 for additional
      furosemide treatment and 654 for hydration alone) were included in the meta
      analysis. In the synthesis of data, additional furosemide administration had
      little impact on the incidence of CIN post-PCI compared with peri-procedural
      saline hydration alone (OR=0.96; 95% CI 0.33-2.84, p=0.95). Moreover, as for the
      subsequent need for dialysis, there was no statistical significant difference
      between the 2 groups (OR=1.01; 95% CI 0.38-2.67, p=0.99). Sensitivity analyses
      did not show any relevant influence on the overall results. There was no
      publication bias in the meta-analysis. CONCLUSIONS: Furosemide administration did
      not achieve additional benefit beyond saline hydration in reducing the incidence
      of CIN in patients undergoing PCI.

PMID- 25613018
TI  - Brazilin inhibits amyloid beta-protein fibrillogenesis, remodels amyloid fibrils
      and reduces amyloid cytotoxicity.
AB  - Soluble amyloid beta-protein (Abeta) oligomers, the main neurotoxic species, are
      predominantly formed from monomers through a fibril-catalyzed secondary
      nucleation. Herein, we virtually screened an in-house library of natural
      compounds and discovered brazilin as a dual functional compound in both Abeta42
      fibrillogenesis inhibition and mature fibril remodeling, leading to significant
      reduction in Abeta42 cytotoxicity. The potent inhibitory effect of brazilin was
      proven by an IC50 of 1.5 +/- 0.3 MUM, which was smaller than that of (-)
      epigallocatechin gallate in Phase III clinical trials and about one order of
      magnitude smaller than those of curcumin and resveratrol. Most importantly, it
      was found that brazilin redirected Abeta42 monomers and its mature fibrils into
      unstructured Abeta aggregates with some beta-sheet structures, which could
      prevent both the primary nucleation and the fibril-catalyzed secondary
      nucleation. Molecular simulations demonstrated that brazilin inhibited Abeta42
      fibrillogenesis by directly binding to Abeta42 species via hydrophobic
      interactions and hydrogen bonding and remodeled mature fibrils by disrupting the
      intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental
      and computational studies revealed a different working mechanism of brazilin from
      that of known inhibitors. These findings indicate that brazilin is of great
      potential as a neuroprotective and therapeutic agent for Alzheimer's disease. 

PMID- 25613023
TI  - Renal purinergic signalling in health and disease.

PMID- 25613020
TI  - Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of
      Contextual Fear Memory.
AB  - Fear is crucial for survival, whereas hypermnesia of fear can be detrimental.
      Inhibition of the Rac GTPase is recently reported to impair the forgetting of
      initially acquired memory in Drosophila. Here, we investigated whether inhibition
      of Rac1 activity in rat hippocampus could contribute to the hypermnesia of
      contextual fear. We found that spaced but not massed training of contextual fear
      conditioning caused inhibition of Rac1 activity in the hippocampus and heightened
      contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor
      NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04
      A weakened contextual fear in spaced training rats. Our study firstly
      demonstrates that contextual fear memory in rats is actively regulated by Rac1
      activity in the hippocampus, which suggests that the forgetting impairment of
      traumatic events in posttraumatic stress disorder may be contributed to the
      pathological inhibition of Rac1 activity in the hippocampus. 

PMID- 25613024
TI  - Droplet based microfluidics: spectroscopic characterization of levofloxacin and
      its SERS detection.
AB  - Levofloxacin (Levo), a second generation fluoroquinolone, has both clinical and
      environmental relevance. Therefore, the implementation of fast, robust and cost
      effective techniques for its monitoring is required. Here, its spectroscopic
      characterization and its detection in aqueous environment were carried out using
      surface enhanced Raman spectroscopy combined with droplet based microfluidics.
      The Levo molecule interacts with the silver nanoparticles via the carboxylate
      group and it adopts an upright or slightly tilted orientation. Furthermore, it is
      shown that the presence of Cl(-) ions has a strong influence on the enhancement
      efficiency of the Raman signal of the target molecule. Thus, for the
      determination of the limit of detection (LOD) the measurements were carried out
      in the absence of any electrolytes. The estimated LOD is ~0.8 MUM and the linear
      dynamic window ranges between 1-15 MUM. These results were achieved after the
      normalization of the SERS signal to the Raman mode at 230 cm(-1). This band was
      attributed to the nu(Ag-O) stretching and it accounts for the Levo molecules in
      the first layer on the Ag nanoparticles. 

PMID- 25613019
TI  - Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a beta
      Arrestin 2-Dependent Manner.
AB  - Valproate exposure is associated with increased risks of autism spectrum
      disorder. To date, the mechanistic details of disturbance of melatonin receptor
      subtype 1 (MTNR1A) internalization upon valproate exposure remain elusive. By
      expressing epitope-tagged receptors (MTNR1A-EGFP) in HEK-293 and Neuro-2a cells,
      we recorded the dynamic changes of MTNR1A intracellular trafficking after
      melatonin treatment. Using time-lapse confocal microscopy, we showed in living
      cells that valproic acid interfered with the internalization kinetics of MTNR1A
      in the presence of melatonin. This attenuating effect was associated with a
      decrease in the phosphorylation of PKA (Thr197) and ERK (Thr202/Tyr204). VPA
      treatment did not alter the whole-cell currents of cells with or without
      melatonin. Furthermore, fluorescence resonance energy transfer imaging data
      demonstrated that valproic acid reduced the melatonin-initiated association
      between YFP-labeled beta-arrestin 2 and CFP-labeled MTNR1A. Together, we suggest
      that valproic acid influences MTNR1A intracellular trafficking and signaling in a
      beta-arrestin 2-dependent manner. 

PMID- 25613026
TI  - In vivo evaluation of novel ketal-based oligosaccharides of hyaluronan micelles
      as multifunctional CD44 receptor-targeting and tumor pH-responsive carriers.
AB  - In this report, the oligosaccharides of hyaluronan (oHA)-histidine-menthone 1,2
      glycerol ketal (MGK) (oHM) carried pH-sensitive MGK as hydrophobic moieties and
      oHA as the target of the CD44 receptor. The oHM could self-assemble, with a
      diameter of 65 nm. The cellular uptake, indicated by the fluorescent signals, was
      higher at 4 h. The ex vivo imaging indicated that micelles have a longer blood
      circulation, beyond 5 h. The fluorescence intensity of the micelles in the liver
      and spleen was much higher from 5 to 24 h. The CD44 receptor-targeting, indicated
      by the fluorescence signals of A549 and MDA-MB-231 group, were higher than those
      of the HepG2 and the control. 

PMID- 25613027
TI  - Magnetic nanoparticles as potential candidates for biomedical and biological
      applications.
AB  - Magnetic iron oxide nanoparticles have become the main candidates for biomedical
      and biological applications, and the application of small iron oxide
      nanoparticles in in vitro diagnostics has been practiced for about half a
      century. Magnetic nanoparticles (MNPs), in combination with an external magnetic
      field and/or magnetizable grafts, allow the delivery of particles to the chosen
      target area, fix them at the local site while the medication is released, and act
      locally. In this review, we focus mostly on the potential use of MNPs for
      biomedical and biotechnological applications, and the improvements made in using
      these nanoparticles (NPs) in biological applications. 

PMID- 25613028
TI  - In vitro and in vivo evaluation of porous TiNi-based alloy as a scaffold for cell
      tissue engineering.
AB  - This study aims to look into the applicability of a porous TiNi-based shape
      memory alloy (SMA) scaffold as an incubator for bone marrow mesenchymal cells,
      hepatocytes, and pancreatic islet cells. The porous TiNi-based SMA used was
      fabricated using a self-propagating high-temperature synthesis (SHS) technique,
      in which scaffold blocks measuring 4 * 4 * 10 mm were prepared. In vitro tests
      were done using mesenchymal stem cells (MSC) isolated from mature bone marrow of
      CBA/j inbred mice, and cultured in 3 different culture media - Control medium,
      Osteogenic medium, and Chondrogenic medium. Hepatocytes and islet cells were
      isolated from the livers and pancreatic glands of Wistar rats respectively,
      seeded on porous TiNi-based SMA scaffolds, and cultured. The scaffolds were then
      implanted into the abdominal cavity of Wistar rats and later harvested, at days
      7, 14, 21, and 28, post-implantation. SEM imaging was performed with pre
      implanted scaffolds at day 0 and harvested scaffolds at days 7, 14, 21, and 28,
      post-implantation. Based on weight increase percentages, the in vitro study
      revealed that the osteogenic group showed a 2-fold increase, and the chondrogenic
      group showed a 1.33-fold increase, compared to the control group. The in vivo
      study, on the other hand, showed that from day 7 post-implantation, the cellular
      in-growth gradually invaded the inner porous structure from the periphery towards
      the center, and at day-28 post-implantation, all pores were closed and completely
      filled with cells and the extracellular matrix. The results show that porous TiNi
      based SMA is a unique biocompatible incubator for cell cultures and can be
      successfully used for tissue bioengineering and artificial organs. 

PMID- 25613029
TI  - Optimized osteogenic differentiation protocol from R1 mouse embryonic stem cells
      in vitro.
AB  - Embryonic stem cells (ESCs) are a unique model that allows the study of molecular
      pathways underlying commitment and differentiation. One such lineage is
      osteoblasts, which are responsible for forming bone tissue in the body. There are
      many osteogenic differentiation protocols in the literature utilizing different
      soluble factors. The goal of the present study was to increase the efficacy of
      our osteogenic differentiation protocol from R1 cells. We have studied the
      effects of the addition of the following factors: dexamethasone, retinoic acid,
      and peroxisome-proliferator-activated receptor-gamma inhibitor, which have been
      reported to enhance osteogenesis. We found that among the 6 different protocols
      that were tested, the addition of retinoic acid with later addition of
      dexamethasone gives the most enrichment of osteogenic lineage cells. Thus, our
      findings provide valuable guidelines for culture condition to differentiate mouse
      R1 ESCs to osteoblastic cells in vitro. 

PMID- 25613030
TI  - Targeting apoptotic pathways in myocardial infarction: attenuated by
      phytochemicals.
AB  - Myocardial infarction (MI) is an insidious disease, gently spreading in developed
      and developing countries. MI is the consequence of hypoxia in myocardial tissue,
      which may lead to apoptosis, narcosis and followed by cardiac cell death.
      Activation of apoptotic pathways during MI is frequently reported in clinical,
      preclinical and post-mortem studies. Several mediators of apoptosis signalling
      cascades culminate into MI leading to cardiomyocytes death. Such involvements of
      ischemia-induced apoptosis in MI are widely accepted. Apoptosis is a natural
      phenomenon for regulating the homeostasis in cellular organelles. Unlike the
      necrosis, it is a synchronized energy dependent process which is carried out by
      shrinkage of the cell. This contraction of cells leads to squeezing of nuclei and
      nuclear chromatin into brusquely demarcated masses. However, such programmed cell
      death in several tissues, including the myocardium becomes pathogenic under
      certain conditions. Moreover, reactive oxygen species (ROS) generated oxidative
      stress also plays a key role in production of apoptosis and several associated
      signalling alterations which ultimately lead to MI. Recently, certain natural
      products, especially from the plant kingdom have been evaluated for their anti
      apoptotic potential. There is an uprise in the investigations delineating the
      exact mechanisms through which natural phytochemicals target apoptosis associated
      MI. This review explores novel signalling pathways and target sites for anti
      apoptotic phytochemicals having potential to check the cellular apoptosis
      consequent to MI. A new vista may explore the prospective treatment of MI by
      using apoptosis-modulating natural products. 

PMID- 25613031
TI  - Early growth response-1 (EGR-1) - a key player in myocardial cell injury.
AB  - Coronary heart disease is the leading cause of mortality worldwide, affecting
      millions of men and women every year. Elucidation of key signaling factors and
      their pathways are critical for understanding and developing novel therapeutic
      targets for protection of the myocardium from ischemia. EGR-1, an immediate early
      gene and a zinc finger transcription factor plays critical role in various
      cardiovascular patho-biological processes. This article reviews the growing
      evidence implicating EGR-1 pathway in myocardial ischemia/reperfusion, cardiac
      hypertrophy and other cardiovascular complications like atherosclerosis. 

PMID- 25613032
TI  - Role of alpha-crystallin B in regulation of stress induced cardiomyocyte
      apoptosis.
AB  - Cardiovascular disease is the leading cause of death worldwide. Recently emerging
      evidence suggests that cardiomyocyte apoptosis is one of the major pathogenic
      factors in heart diseases leading to heart failure. Cardiomyocytes undergo
      apoptosis in response to a wide variety of cellular stresses including protein
      folding stress at Endoplasmic reticulum (ER). Stressed myocytes elicit an
      adaptive response referred as Unfolded Protein Response (UPR) by inducing
      accumulation of heat shock proteins (HSPs) to mitigate the ER stress. HSPs act as
      molecular chaperons by assisting correct folding of the aggregated misfolded
      proteins in ER lumen. alpha-Crystallin B (CRYAB) is an abundant small HSP that
      confers protection to cardiomyocytes against various stress stimuli. Recent
      evidence indicates that CRYAB directly interacts with several components of ER
      stress and also mitochondrial apoptotic pathway. Based on currently available
      literature this mini review will focus on how CRYAB confers protection to
      stressed myocardium thereby emphasizing its function as antiapoptotic molecule.
      Understanding the interplay between CRYAB and the key components in the apoptotic
      signaling cascade mediated by ER and mitochondria will help in development of
      novel therapies for cardiac diseases. 

PMID- 25613033
TI  - Axonal damage in papilledema linked to idiopathic intracranial hypertension as
      revealed by multifocal visual evoked potentials.

PMID- 25613034
TI  - Seizures induced by direct electrical cortical stimulation--Mechanisms and
      clinical considerations.
AB  - Direct electrical cortical stimulation (CS) is widely used to map eloquent
      cortex. It can be applied extraoperatively in patients undergoing intracranial
      EEG recordings using chronically implanted electrodes (subdural, depth or a
      combination), or it can be used intraoperatively. Seizures can be induced by CS
      but there is controversy regarding the utility of CS induced seizures in defining
      the epileptogenic zone and hence practice varies considerably between centres.
      Some centres use seizures induced by direct CS routinely to aid in defining the
      epileptogenic zone. In contrast, others do not rely on such information and
      explicitly avoid stimulating seizures during cortical mapping. Intra- and
      extraoperative techniques have been used to stimulate seizures with varying
      results, which may in part reflect these methodological differences. We here aim
      to review current views, definitions and studies on seizures induced by direct
      electrical CS. In addition we discuss mechanisms and methodological
      considerations of this procedure. 

PMID- 25613035
TI  - Jurors report that risk measure scores matter in sexually violent predator
      trials, but that other factors matter more.
AB  - After deliberating to a verdict, jurors (N = 462) from 40 sexually violent
      predator (SVP) trials completed a questionnaire asking them to rate the extent to
      which risk measure scores, diagnoses, expert witness testimony, and offender
      characteristics described during the trials influenced their commitment
      decisions. Jurors reported that offenders' sexual offending history, failure to
      change, and lack of remorse had the strongest influence on their commitment
      decisions. They reported that testimony about risk instrument scores (e.g.,
      Static-99) and psychopathy had less influence on their decisions, but those who
      did report being influenced by instrument results were especially likely to view
      the offender as being at a high risk for reoffending. Overall, findings suggest
      that SVP jurors view risk measure results as important, but not as important as
      other offender, offense, and testimony characteristics, including some that have
      limited relevance to recidivism risk. Thus, findings also suggest that experts
      may need to better educate jurors regarding factors that do and do not relate to
      recidivism risk.

PMID- 25613036
TI  - Anti-cancer effect of metabotropic glutamate receptor 1 inhibition in human
      glioma U87 cells: involvement of PI3K/Akt/mTOR pathway.
AB  - BACKGROUND: Metabotropic glutamate receptors (mGluRs) are G-protein-coupled
      receptors that mediate neuronal excitability and synaptic plasticity in the
      central nervous system, and emerging evidence suggests a role of mGluRs in the
      biology of cancer. Previous studies showed that mGluR1 was a potential
      therapeutic target for the treatment of breast cancer and melanoma, but its role
      in human glioma has not been determined. METHODS: In the present study, we
      investigated the effects of mGluR1 inhibition in human glioma U87 cells using
      specific targeted small interfering RNA (siRNA) or selective antagonists Riluzole
      and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by
      cell viability, lactate dehydrogenase (LDH) release, TUNEL staining, cell cycle
      assay, cell invasion and migration assays in vitro, and also examined in a U87
      xenograft model in vivo. RESULTS: Inhibition of mGluR1 significantly decreased
      the cell viability but increased the LDH release in a dose-dependent fashion in
      U87 cells. These effects were accompanied with the induction of caspase-dependent
      apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel
      invasion and cell tracking assays showed that inhibition of mGluR1 apparently
      attenuated cell invasion and migration in U87 cells. All these anti-cancer
      effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of
      western blot analysis showed that mGluR1 inhibition overtly decreased the
      phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated
      activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1
      inhibition in vivo was also demonstrated in a U87 xenograft glioma model in
      athymic nude mice. CONCLUSION: The remarkable efficiency of mGluR1 inhibition to
      induce cell death in U87 cells may find therapeutic application for the treatment
      of glioma patients.

PMID- 25613037
TI  - Uncorrected and Albumin-Corrected Calcium, Phosphorus, and Mortality in Patients
      Undergoing Maintenance Dialysis.
AB  - Uncorrected serum calcium concentration is the first mineral metabolism metric
      planned for use as a quality measure in the United States ESRD population. Few
      studies in patients undergoing either peritoneal dialysis (PD) or hemodialysis
      (HD) have assessed the association of uncorrected serum calcium concentration
      with clinical outcomes. We obtained data from 129,076 patients on dialysis (PD,
      10,066; HD, 119,010) treated in DaVita, Inc. facilities between July 1, 2001, and
      June 30, 2006. After adjustment for potential confounders, uncorrected serum
      calcium <8.5 and >=10.2 mg/dl were associated with excess mortality in patients
      on PD or HD (comparison group uncorrected calcium 9.0 to <9.5 mg/dl). Additional
      adjustment for serum albumin concentration substantially attenuated the all-cause
      mortality hazard ratios (HRs) associated with uncorrected calcium <8.5 mg/dl (HR,
      1.29; 95% confidence interval [95% CI], 1.16 to 1.44 for PD; HR, 1.17; 95% CI,
      1.13 to 1.20 for HD) and amplified the HRs associated with calcium >=10.2 mg/dl
      (HR, 1.65; 95% CI, 1.42 to 1.91 for PD; HR, 1.59; 95% CI, 1.53 to 1.65 for HD).
      Albumin-corrected calcium >=10.2 mg/dl and serum phosphorus >=6.4 mg/dl were also
      associated with increased risk for death, irrespective of dialysis modality. In
      summary, in a large nationally representative cohort of patients on dialysis,
      abnormalities in markers of mineral metabolism, particularly high concentrations
      of serum calcium and phosphorus, were associated with increased mortality risk.
      Additional studies are needed to investigate whether control of hypercalcemia and
      hyperphosphatemia in patients undergoing dialysis results in improved clinical
      outcomes. 

PMID- 25613038
TI  - Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized
      synovial sarcoma: is chemotaxis important to tumor response?
AB  - BACKGROUND: Synovial sarcoma (SS) is a rare tumor, with dismal survival when
      metastatic. The role of adjuvant chemotherapy is debated. New prognostic and
      predictive factors are needed. METHODS: We reviewed patients with localized SS;
      SS18-SSX fusion transcript presence was confirmed by FISH and RT-PCR. Expression
      of CXCR4, IGF-1R and Ezrin were evaluated by immunohistochemistry. RESULTS: Tumor
      samples from 88 SS patients (45 female; 43 male) with median age 37 years (range
      11-63) were selected. The size of the lesion was > 5 cm in 68% of patients and
      34% of cases presented biphasic histotype. All patients underwent surgery, 56%
      adjuvant radiotherapy (RT), 65% adjuvant chemotherapy. A positive stain for IGF
      1R was detected in 55 patients, with nucleus expression in 21 patients. CXCR4 was
      expressed in 74 patients, nuclear pattern in 31 patients. 80 SS were positive to
      Ezrin, 48 had cytoplasmatic location, 32 membrane location. With a median follow
      up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (95% CI 60
      81). 5-year OS was 63% (95% CI 41-85%) for patients with positive IGF-1R/nuclear
      expression, and 73% (95% CI 61-85%; P = 0.05) in negative patients. 5-year OS was
      47% (95% CI 27-66%) in patients with positive CXCR4/nuclear staining, and 86%
      (95% CI 76-96%, P = 0.0003) in negative cases. No survival difference was found
      according to Ezrin expression. By multivariate analysis, nuclear expression of
      CXCR4 and IGF-1R was confirmed independent adverse prognostic factor for SS
      patient survival linked to the use of chemotherapy. CONCLUSIONS: Our findings
      have important potential implications demonstrating that together with clinical
      prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively
      influences survival in patients with localized SS. We believe that further
      studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability
      and function are needed to plan new and more appropriate SS treatments.

PMID- 25613039
TI  - Capacity of patients with brain metastases to make treatment decisions.
AB  - OBJECTIVE: The aim of this study was to investigate medical decision-making
      capacity (MDC) in patients with brain metastases. METHODS: Participants were 41
      adults with brain metastases with Karnofsky Performance Status scores of >=70 who
      were recruited from an academic medical center and 41 demographically matched
      controls recruited from the community. We evaluated MDC using the Capacity to
      Consent to Treatment Instrument and its four clinically relevant consent
      standards (expressing a treatment choice, appreciation, reasoning, and
      understanding). Capacity impairment ratings (no impairment, mild/moderate
      impairment, and severe impairment) on the consent standards were also assigned to
      each participant with brain metastasis using cutoff scores derived statistically
      from the performance of the control group. RESULTS: The brain metastasis patient
      group performed significantly below controls on consent standards of
      understanding and reasoning. Capacity compromise was defined as performance <=1.5
      standard deviations below the control group mean. Using this definition,
      approximately 60% of the participants with brain metastases demonstrated capacity
      compromise on at least one MDC standard. CONCLUSION: When defining capacity
      compromise as performance <=1.5 standard deviation below the control group mean,
      over half of patients with brain metastases have reduced capacity to make
      treatment decisions. This impairment is demonstrated shortly after initial
      diagnosis of brain metastases and highlights the importance of routine clinical
      assessment of MDC following diagnosis of brain metastasis. These results also
      indicate a need for the development and investigation of interventions to support
      or improve MDC in this patient population.

PMID- 25613040
TI  - Real-time polymerase chain reaction assays for the detection and quantification
      of Edwardsiella tarda, Edwardsiella piscicida, and Edwardsiella piscicida-like
      species in catfish tissues and pond water.
AB  - Researchers have proposed the adoption of 3 distinct genetic taxa among bacteria
      previously classified as Edwardsiella tarda; namely E. tarda, E. piscicida, and a
      taxon presently termed E. piscicida-like. Individual real-time polymerase chain
      reaction (qPCR) assays were developed, based on published primers, for E. tarda,
      E. piscicida, and E. piscicida-like sp. to provide rapid quantitative
      confirmatory tests for these phenotypically ambiguous bacteria. The qPCR assays
      were shown to be repeatable and reproducible, with high degrees of sensitivity
      and specificity. Each assay showed a linear dynamic range covering 8 orders of
      magnitude and a sensitivity limit of 5 copies of target DNA in a 15-uL reaction.
      In addition, each assay was found specific to their respective targets with no
      observed amplification from nontarget organisms, including the closely related E.
      ictaluri and E. hoshinae. Under the conditions used in this study, the 3 assays
      had a quantifiable limit ranging from 10(3) (E. piscicida) to 10(2) (E. piscicida
      like and E. tarda) colony forming units in kidney tissue biopsies (approximately
      25 mg), pond water samples (35 mL), and broth culture (20 MUL). In experimental
      challenges, the assays were able to detect their respective targets in both
      clinically and subclinically infected channel catfish (Ictalurus punctatus)
      fingerlings. In addition to quantifying target bacteria from various substrates,
      the assays provide rapid identification, differentiation, and confirmation of the
      phenotypically indistinguishable E. tarda, E. piscicida, and E. piscicida-like
      sp., a valuable tool for diagnostic assessments. 

PMID- 25613041
TI  - Erysipelothrix rhusiopathiae and Mycoplasma hyopneumoniae: the sensitivities of
      enzyme-linked immunosorbent assays for detecting vaccinated sows of unknown
      disease status using serum and colostrum, and the correlation of the results for
      sow serum, colostrum, and piglet serum.
AB  - Due to relatively high concentrations of immunoglobulins, colostrum has the
      potential to improve the sensitivity of diagnostic tests for diseases in pigs
      when compared with serum. It is possible that colostrum could improve the
      sensitivity of the antibody enzyme-linked immunosorbent assay (ELISA) compared
      with serum. Colostrum is also essential for piglets, providing protection against
      infections in the first few weeks and months of life. The sensitivity of 2
      commercially available ELISAs, one for the detection of Erysipelothrix
      rhusiopathiae and the second for Mycoplasma hyopneumoniae antibodies, when used
      with sow colostrum in comparison with serum was investigated. The correlation of
      maternal E. rhusiopathiae- and M. hyopneumoniae-specific antibody levels with
      specific-antibody serum levels in the piglet was also determined. The sensitivity
      was defined as the proportion of vaccinated sows that were correctly identified
      as vaccinated at a given cutoff point. The true disease status of the sows with
      regard to the 2 infections was unknown. Blood and colostrum samples were
      collected from 20 sows, 10 primiparous and 10 multiparous, and blood samples were
      also collected from the piglets of each sow, 48-72 hr post-farrowing. The
      sensitivities of both ELISAs were significantly improved when using colostrum
      compared with serum. Sow serum and colostrum optical density (OD) values were
      significantly correlated. The mean sow OD values for serum for E. rhusiopathiae
      and M. hyopneumoniae and colostrum for E. rhusiopathiae were significantly
      correlated with piglet serum OD levels. If the improved sensitivity of colostrum
      can be demonstrated in infected animals, this will increase the ability of the
      test to identify infected animals using both individual and pooled colostrum.
      Testing serum and/or colostrum using ELISA can be useful predictors of piglet
      disease-specific OD values. 

PMID- 25613042
TI  - Liposarcoma in animals: literature review and case report in a domestic pig (Sus
      scrofa).
AB  - Liposarcomas are malignant tumors of adipocytes. The current report describes a
      liposarcoma in a 2.5-year-old, mixed-breed commercial sow that was detected
      during meat inspection. On gross examination, a firm, whitish, multinodular, 20
      cm *10 cm mass was observed in the perirenal area along with smaller nodules
      multifocally scattered within the renal parenchyma. Histological examination
      revealed an anaplastic sarcoma with clear intracytoplasmic lipidic vacuoles that
      were positive for Sudan black staining. Most of the cells were also positive for
      S100 and vimentin immunohistochemistry. Based on these results, a diagnosis of a
      perirenal liposarcoma was established. To the authors' knowledge, no previous
      reports of liposarcomas in pigs have been published. This report also includes a
      review of the literature published on animal liposarcomas. 

PMID- 25613043
TI  - Multiple oral carcinomas associated with a novel papillomavirus in a dog.
AB  - Papillomaviruses (PVs) are well recognized to cause human oral squamous cell
      carcinomas (SCCs). However, there is currently little evidence that PVs similarly
      cause oral cancer in dogs. In the present case, a dog developed an invasive SCC
      and multiple in situ carcinomas within the mouth. Cell changes consistent with PV
      infection were prominent within the neoplasms and the surrounding gingiva.
      Immunohistochemical staining revealed PV antigens and intense p16(CDKN2A) protein
      (p16) immunostaining within the invasive SCC. Papillomaviral DNA sequences were
      amplified from the invasive and in situ carcinomas. Sequencing revealed that the
      DNA was from a novel PV that appears most closely related to canine PV-2 and -7.
      To the authors' knowledge, multiple carcinomas have not been previously reported
      in the mouth of a dog. Additionally, the current study describes PV cytopathology
      in a canine oral SCC. Whether the PV infection influenced neoplasm development
      cannot be definitively determined in this case. However, the presence of p16
      immunostaining and the development of multiple oral carcinomas support a role of
      the PV in tumorigenesis in this dog. 

PMID- 25613044
TI  - Productivity responses of desert vegetation to precipitation patterns across a
      rainfall gradient.
AB  - The influences of previous-year precipitation and episodic rainfall events on
      dryland plants and communities are poorly quantified in the temperate desert
      region of Northwest China. To evaluate the thresholds and lags in the response of
      aboveground net primary productivity (ANPP) to variability in rainfall pulses and
      seasonal precipitation along the precipitation-productivity gradient in three
      desert ecosystems with different precipitation regimes, we collected
      precipitation data from 2000 to 2012 in Shandan (SD), Linze (LZ) and Jiuquan (JQ)
      in northwestern China. Further, we extracted the corresponding MODIS Normalized
      Difference Vegetation Index (NDVI, a proxy for ANPP) datasets at 250 m spatial
      resolution. We then evaluated different desert ecosystems responses using
      statistical analysis, and a threshold-delay model (TDM). TDM is an integrative
      framework for analysis of plant growth, precipitation thresholds, and plant
      functional type strategies that capture the nonlinear nature of plant responses
      to rainfall pulses. Our results showed that: (1) the growing season NDVIINT (INT
      stands for time-integrated) was largely correlated with the warm season
      (spring/summer) at our mildly-arid desert ecosystem (SD). The arid ecosystem (LZ)
      exhibited a different response, and the growing season NDVIINT depended highly on
      the previous year's fall/winter precipitation and ANPP. At the extremely arid
      site (JQ), the variability of growing season NDVIINT was equally correlated with
      the cool- and warm-season precipitation; (2) some parameters of threshold-delay
      differed among the three sites: while the response of NDVI to rainfall pulses
      began at about 5 mm for all the sites, the maximum thresholds in SD, LZ, and JQ
      were about 55, 35 and 30 mm respectively, increasing with an increase in mean
      annual precipitation. By and large, more previous year's fall/winter
      precipitation, and large rainfall events, significantly enhanced the growth of
      desert vegetation, and desert ecosystems should be much more adaptive under
      likely future scenarios of increasing fall/winter precipitation and large
      rainfall events. These results highlight the inherent complexity in predicting
      how desert ecosystems will respond to future fluctuations in precipitation.

PMID- 25613045
TI  - Comparative proteomic analysis of hyphae and germinating cysts of Phytophthora
      pisi and Phytophthora sojae.
AB  - The recently described oomycete pathogen Phytophthora pisi causes root rot on pea
      and faba bean, while the closely related Phytophthora sojae is the causal agent
      of soybean root and stem rot. Differences in the pathogenicity factor repertoires
      that enable the two species to have distinct host specificity towards pea and
      soybean, were studied using tandem mass spectrometry in a global proteome study
      of hyphae and germinating cysts in P. pisi and P. sojae. In total 2775 proteins
      from P. pisi and 2891 proteins from P. sojae were identified. Fifty-eight
      orthologous proteins were more abundant in germinated cysts of both pathogens and
      thus identified as candidate proteins for the infective stage. Several of these
      proteins were associated with lipid transport and metabolism, and energy
      production. Twenty-three orthologous proteins were more abundant in hyphae of
      both pathogens and thus identified as candidate proteins for vegetative growth.
      Proteins uniquely present in germinating cysts of either P. pisi or P. sojae were
      considered as candidates for species-specific pathogenicity factors that may be
      involved in host specificity. Among these proteins were serine proteases,
      membrane transporters and a berberine-like protein. These results significantly
      expand the knowledge of the expressed proteome in P. pisi and P. sojae.
      BIOLOGICAL SIGNIFICANCE: P. sojae and P. pisi are closely related species that
      specifically cause root rot on soybean and pea, respectively. The pathogenicity
      factors contributing to their host specificity remained unknown. We carried out a
      comparative large-scale proteome analysis of vegetative (hyphae) and infective
      (germinating cysts) life stages in P. pisi and P. sojae. This study provides
      knowledge of the common factors and mechanism involved in initiation of infection
      and species-specific proteins that may contribute to the host specificity of
      these pathogens. This knowledge will lead to a better understanding of the
      infection biology of these pathogens, allowing new possibilities towards
      developing alternative and effective plant protection measures.

PMID- 25613046
TI  - Peptide profiling of bovine kefir reveals 236 unique peptides released from
      caseins during its production by starter culture or kefir grains.
AB  - Kefir has a long tradition in human nutrition due to its presupposed health
      promoting effects. To investigate the potential contribution of bioactive
      peptides to the physiological effects of kefir, comprehensive analysis of the
      peptide profile was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano
      ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified,
      mainly released from beta-casein, followed by alphaS1-, kappa-, and alphaS2
      casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk
      indicating that the fermentation step does not only increase the proteolytic
      activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the
      composition of the peptide fraction. The influence of the microflora was
      determined by analyzing kefir produced from traditional kefir grains or
      commercial starter culture. Kefir from starter culture featured 230 peptide
      sequences and showed a significantly, 1.4-fold higher proteolytic activity than
      kefir from kefir grains with 127 peptides. A match of 97 peptides in both
      varieties indicates the presence of a typical kefir peptide profile that is not
      influenced by the individual composition of the microflora. Sixteen of the newly
      identified peptides were previously described as bioactive, including angiotensin
      converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid,
      mineral binding, antioxidant, and antithrombotic effects. BIOLOGICAL
      SIGNIFICANCE: The present study describes a comprehensive peptide profile of
      kefir comprising 257 sequences. The peptide list was used to identify 16
      bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral
      binding, antimicrobial, immunomodulating and opioid activity in kefir.
      Furthermore, it was shown that a majority of the kefir peptides were not
      endogenously present in the raw material milk, but were released from milk
      caseins by proteases of the microbiota and are therefore specific for the
      product. Consequently, the proteolytic activity and the composition of the
      peptide profile can be controlled by the applied microflora (grains or starter
      culture). On the other hand, a considerable portion of the peptide profile was
      identified to be typical for kefir in general and independent from production
      parameters. In summary, the generated kefir peptide profile helped to reveal its
      origin and to identify bioactive peptides in kefir, which may advance the
      understanding of health benefits of this food product. The results further
      indicate that subsets of the kefir peptide list can be used as markers to control
      food authenticity, for example, to distinguish different types of kefir.

PMID- 25613047
TI  - Whole-body vibration therapy in children with severe motor disabilities.
AB  - OBJECTIVE: To study the effect of whole-body vibration therapy on bone mass, bone
      turnover and body composition in severely disabled children. METHODS: Nineteen
      non-ambulatory children aged 5.1-16.3 years (6 males, 13 females) with severe
      motor disabilities participated in an intervention programme with standing
      exercise on a self-controlled dynamic platform, which included whole-body
      vibration therapy (vibration, jump and rotation movements). Whole-body vibration
      therapy was performed at 40-42 Hz, with an oscillation amplitude of 0.2 mm, 5-15
      min/treatment, twice/week for 6 months. Bone mass parameters and bone markers
      were measured at the study start, and after 6 and 12 months. RESULTS: Whole-body
      vibration therapy was appreciated by the children. Total-body bone mineral
      density increased during the study period (p < 0.05). Z-scores for total-body
      bone mineral density ranged from -5.10 to -0.60 at study start and remained
      unchanged throughout. Approximately 50% of the subjects had increased levels of
      carboxy-terminal telopeptides of type I collagen and decreased levels of
      osteocalcin at the start. Body mass index did not change during the intervention
      period, but had increased by the 12-month follow-up (p < 0.05). CONCLUSION: Whole
      body vibration therapy appeared to be well tolerated by children with severe
      motor disabilities. Total-body bone mineral density increased after 6 months of
      whole-body vibration therapy. Higher carboxy-terminal telopeptides of type I
      collagen and lower osteocalcin values indicated that severely disabled children
      have a reduced capacity for bone acquisition.

PMID- 25613048
TI  - Molecular cloning, characterization and differential expression of novel
      phytocystatin gene during tropospheric ozone stress in maize (Zea mays) leaves.
AB  - In this study, a full-length cDNA encoding a novel phytocystatin gene, designated
      CC14, was identified in maize leaves. The CC14 gene sequence reported in this
      study has been deposited in the GenBank database (accession number JF290478). The
      CC14 gene was cloned into an expression vector pET30 EK/LIC and was then
      transformed into Escherichia coli strain BL21 (DE3) pLysS to produce a
      recombinant CC14 protein. The recombinant protein was purified by nickel
      nitrilotriacetic acid affinity chromatography after induction with 1 mM IPTG. The
      purified CC14 protein was electrophoresed on SDS-PAGE and a protein 25 kDa in
      size was observed. Antiprotease activities of the purified recombinant CC14
      protein against cysteine proteases and commercially available papain were tested.
      The results showed that CC14 purified protein suppressed 100% activity of papain
      and 57-86% plant cysteine protease activity. Moreover, an upregulation of CC14
      gene expression was observed after 20 days of ozone stress in maize leaves.
      Together, these observations concurred to conclude that CC14 gene could
      potentially be used as a basis for the development of transgenic crops and
      natural pesticides that resist biotic and abiotic stresses.

PMID- 25613049
TI  - Pulmonary shunt fraction measurement compared to contrast echocardiography in
      hereditary haemorrhagic telangiectasia patients: time to abandon the 100% oxygen
      method?
AB  - BACKGROUND: The presence of pulmonary right-to-left shunting (RLS) is associated
      with severe neurological complications from paradoxical embolisation in patients
      with hereditary haemorrhagic telangiectasia (HHT) and screening is warranted.
      Pulmonary shunt fraction measurement with the 100% oxygen method can be used for
      the detection and quantification of functional pulmonary RLS, although
      transthoracic contrast echocardiography (TTCE) has emerged as the gold standard
      over the last few years. OBJECTIVE: The aim of this study was to determine the
      true diagnostic accuracy of the established 100% oxygen method in detecting
      pulmonary RLS, as compared to TTCE. METHODS: We analysed 628 persons screened for
      HHT between 2004 and 2010, all of whom underwent TTCE. A quantitative 3-point
      grading scale was used to differentiate between minimal, moderate or extensive
      pulmonary RLS on TTCE (grade 1-3, respectively). Additional shunt fraction
      measurement with the 100% oxygen method was pursued in cases of pO2 <13 or <12
      kPa in patients younger or older than 30 years, respectively. A shunt fraction
      >5% was considered pathological. RESULTS: Both TTCE and the 100% oxygen method
      were performed in 210 subjects. Although the presence of a pathological shunt
      fraction correlated with an increased pulmonary shunt grade on TTCE, the 100%
      oxygen method confirmed a >5% shunt fraction in only 51% of patients with
      pulmonary RLS on TTCE (14, 20 and 72% for grade 1, 2 and 3, respectively).
      CONCLUSION: Pulmonary shunt fraction measurement with the 100% oxygen method is
      not a useful screening technique for the detection of pulmonary RLS in HHT as its
      sensitivity is too low and large pulmonary shunts on TTCE may remain undetected
      using this method.

PMID- 25613050
TI  - CORRIGENDUM: Stage of Breast Cancer Progression Influences Cellular Response to
      Activation of the WNT/Planar Cell Polarity Pathway.

PMID- 25613051
TI  - Serotonin syndrome following methylene blue administration during cardiothoracic
      surgery.
AB  - INTRODUCTION: Despite its favorable safety profile, there have been reports of
      methylene blue-induced encephalopathy and serotonin syndrome in patients
      undergoing parathyroidectomy. We report a case of serotonin syndrome following
      methylene blue administration in a cardiothoracic surgery patient. CASE REPORT: A
      59-year-old woman taking preoperative venlafaxine and trazodone was given a
      single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery
      bypass and mitral valve repair. Postoperatively, she was febrile to 38.7 degrees
      C and developed full-body tremors, rhythmic twitching of the perioral muscles,
      slow conjugate roving eye movements, and spontaneous movements of the upper
      extremities. Electroencephalography revealed generalized diffuse slowing
      consistent with toxic encephalopathy, and a computed tomography scan showed no
      acute process. The patient's symptoms were most consistent with a methylene blue
      induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she
      was eventually discharged home. DISCUSSION: Only 2 cases of methylene blue
      induced serotonin syndrome during cardiothoracic surgery have been described in
      the literature, with this report representing the third case. Methylene blue and
      its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A
      which is responsible for serotonin metabolism. Concomitant administration of
      methylene blue with serotonin-modulating agents may precipitate serotonin
      syndrome.

PMID- 25613052
TI  - Candida glabrata and Candida tropicalis in an immunocompetent patient: a case
      report.
AB  - OBJECTIVE: To report a case of Candida glabrata and tropicalis pneumonia in an
      immunocompetent patient. CASE SUMMARY: A 72-year-old male was transferred from an
      outside institution due to worsening respiratory status, acute kidney injury
      secondary to intravenous contrast media, sepsis, and pneumonia with fever and
      leukocytosis. Upon admission, he was initiated on treatment for hospital-acquired
      pneumonia, but was also concomitantly tested for many other opportunistic
      infections due to his recent month-long trip to Ecuador where he participated in
      a tribal treatment for neuropathy that involved direct exposure to dead guinea
      pigs. With completion of cultures and bronchoalveolar lavage, C. glabrata was
      identified in the blood culture and C. glabrata and C. tropicalis in the
      bronchoalveolar lavage specimen. One month later, he was admitted due to
      recurrent pneumonia. The patient unfortunately expired during the second
      admission, due to complications from chronic respiratory pulmonary disease and
      pneumonia. DISCUSSION: Initially, this patient was treated for hospital-acquired
      pneumonia, but due to a recent trip to Ecuador, it was soon discovered that this
      patient had developed an invasive Candida pneumonia. His pulmonary biopsies
      showed growth of invasive C. glabrata and C. tropicalis, while his blood culture
      showed C. glabrata. Candida-related lower respiratory tract infections are
      exceptionally rare in immunocompetent patients and require histopathologic
      evidence to confirm the diagnosis. A second blood culture showed that the C.
      glabrata was still present and the patient had worsening leukocytosis, so
      micafungin was added to his antimicrobial therapy. CONCLUSION: It is understood
      that pneumonia is rarely caused by Candida species in patients who are admitted
      to the hospital. However, health care professionals should be aware that Candida
      pneumonia should be suspected as part of the differential diagnosis even in
      immunocompetent patients, particularly if they have recently traveled outside the
      United States.

PMID- 25613053
TI  - Impact of Nursing Education on the Proportion of Appropriately Drawn Vancomycin
      Trough Concentrations.
AB  - BACKGROUND: Few studies have investigated the timing of vancomycin trough
      concentration collection in the inpatient setting. To date, there are no
      published studies on the impact of targeted nursing staff education on the
      appropriate timing of vancomycin trough concentration collection. OBJECTIVE: To
      evaluate the impact of educational sessions on nursing staff knowledge regarding
      vancomycin and proper collection of troughs. METHODS: The nursing staffs of 5
      hospital units with a high volume of vancomycin usage were targeted for voluntary
      vancomycin educational sessions. Comprehension of the educational content was
      measured by a 5-question pre-/posteducation quiz. Vancomycin trough
      concentrations were evaluated during a 2-month period pre-/posteducation for
      appropriate timing of sample draw, defined as <=45 minutes prior to the next
      scheduled vancomycin dose. RESULTS: A total of 114 nurses participated in the
      education sessions. The mean pretest score was 3.91 and the mean posttest score
      was 4.89 (P < .001). Preeducation, 69% of trough concentrations were collected
      appropriately. Posteducation, 74% of samples were collected within the 45-minute
      time frame (P = .20). CONCLUSIONS: A significant increase in short-term
      comprehension regarding vancomycin was seen posteducation. There was a
      nonsignificant increase in appropriately timed trough concentration collection
      posteducation. Further education of nursing staffs may be necessary to lessen
      timing errors.

PMID- 25613054
TI  - A Survey of Pharmacists in Academia on the Current Practice of Estimation of
      Kidney Function for Antimicrobial Dosing in Adults.
AB  - PURPOSE: To determine the methods used by pharmacists in academia to estimate
      kidney function for antimicrobial dosing. METHODS: Stratified by region, a random
      sample of Accreditation Council for Pharmacy Education recognized Colleges of
      Pharmacy was selected for a total of 40 programs. Identified college Web sites
      were reviewed for eligible participants using the predefined inclusion/exclusion
      criteria. This was used to create a sampling frame from which 30% and 20% of
      faculty were randomly chosen and invited to participate via e-mail and mail
      administered surveys, respectively. RESULTS: Of the responders, 86% (31 of 36)
      who routinely estimate kidney function utilized the Cockcroft-Gault (CG)
      equation. In obese patients, 75% utilized the CG equation with or without
      adjustments. In patients >=65 years, 42% adjusted serum creatinine to 1 mg/dL and
      25% did not make any modifications. The majority of the responders accounted for
      patients with quadripalegia or bed-bound patients when estimating kidney
      function. In scenario examples, 51% (18 of 35) dosed an elderly female and 51%
      (18 of 35) a morbidly obese female as creatinine clearance >=50 mL/min; however,
      49% (17 of 35) did not. CONCLUSION: The majority of responders utilized the CG
      equation for estimating kidney function with or without adjustments. Although a
      number of consistencies were noted, discrepancies existed, especially with
      elderly and obese patients.

PMID- 25613055
TI  - Survey Evaluation of Pharmacy Practice Involving Deaf Patients.
AB  - INTRODUCTION: For a patient who is deaf, providing patient care can be more
      difficult due to communication barriers. This study was conducted in order to
      better understand pharmacists' current means of communicating with deaf patients
      as well as investigating pharmacists' knowledge of their legal responsibility to
      these patients. METHODS: Surveys were used to gather information from pharmacists
      and were distributed in areas with a large population of deaf patients. RESULTS:
      Of the 73 pharmacists who completed surveys, 50 (68.5%) of them interact with at
      least 1 to 5 deaf patients monthly. Pharmacists responded that accessibility of
      interpreters is the most significant barrier to communication and providing
      written material is the method most used to communicate with deaf patients. None
      of the 73 pharmacists who completed the survey felt that they have a legal
      obligation to provide and pay for an interpreter. CONCLUSION: When interacting
      with a deaf patient, pharmacists may experience communication barriers.
      Pharmacists should strive to appropriately communicate with the deaf as well as
      familiarize themselves with legal obligations to this patient population.

PMID- 25613056
TI  - Luminal Toxin-Binding Agents for Clostridium difficile Infection.
AB  - OBJECTIVE: To systematically search the literature for trials evaluating luminal
      toxin-binding agents (LTBAs) for Clostridium difficile infection (CDI). METHODS:
      A systematic search was conducted utilizing PubMed and International
      Pharmaceutical Abstracts with the following terms: anion-exchange resins, C
      difficile, cholestyramine, tolevamer, and colestipol. Articles were included if
      published in the English language and reported clinical outcomes of more than 5
      adult humans with CDI treated with LTBAs. RESULTS: Nearly all clinical trials
      evaluated LTBA as monotherapy for CDI and LTBAs are inferior to standard therapy.
      In contemporary practice, LTBAs are employed as adjunctive or sequential therapy
      for which there is a paucity of data. Some data suggest potential efficacy for
      recurrent CDI. Current guidelines for CDI assert LTBAs are contraindicated due to
      drug-drug interactions with vancomycin. However, the impact of this interaction
      on clinical outcomes has not been evaluated, and it is unknown whether higher
      doses of vancomycin or separating the administration of LTBAs from vancomycin
      would mitigate this interaction. CONCLUSION: LTBA monotherapy is inferior to
      vancomycin and metronidazole for CDI. Some data indicate possible benefit in
      reducing recurrent CDI, but outcomes with adjunctive and/or sequential LTBAs are
      unavailable. Further studies are needed to investigate the role of LTBAs for CDI.

PMID- 25613057
TI  - Validity and Reliability of a Systematic Database Search Strategy to Identify
      Publications Resulting From Pharmacy Residency Research Projects.
AB  - PURPOSE: This study aims to develop a systematic search strategy and test its
      validity and reliability in terms of identifying projects published in peer
      reviewed journals as reported by residency graduates through an online survey.
      METHODS: This study was a prospective blind comparison to a reference standard.
      Pharmacy residency projects conducted at the study institution between 2001 and
      2012 were included. A step-wise, systematic procedure containing up to 8 search
      strategies in PubMed and EMBASE for each project was created using the names of
      authors and abstract keywords. In order to further maximize sensitivity, complex
      phrases with multiple variations were truncated to the root word. Validity was
      assessed by obtaining information on publications from an online survey deployed
      to residency graduates. RESULTS: The search strategy identified 13 publications
      (93% sensitivity, 100% specificity, and 99% accuracy). Both methods identified a
      similar proportion achieving publication (19.7% search strategy vs 21.2% survey,
      P = 1.00). Reliability of the search strategy was affirmed by the perfect
      agreement between 2 investigators (k = 1.00). CONCLUSION: This systematic search
      strategy demonstrated a high sensitivity, specificity, and accuracy for
      identifying publications resulting from pharmacy residency projects using
      information available in residency conference abstracts.

PMID- 25613058
TI  - High-resolution genetic mapping of allelic variants associated with cell wall
      chemistry in Populus.
AB  - BACKGROUND: QTL cloning for the discovery of genes underlying polygenic traits
      has historically been cumbersome in long-lived perennial plants like Populus.
      Linkage disequilibrium-based association mapping has been proposed as a cloning
      tool, and recent advances in high-throughput genotyping and whole-genome
      resequencing enable marker saturation to levels sufficient for association
      mapping with no a priori candidate gene selection. Here, multiyear and
      multienvironment evaluation of cell wall phenotypes was conducted in an
      interspecific P. trichocarpa x P. deltoides pseudo-backcross mapping pedigree and
      two partially overlapping populations of unrelated P. trichocarpa genotypes using
      pyrolysis molecular beam mass spectrometry, saccharification, and/ or traditional
      wet chemistry. QTL mapping was conducted using a high-density genetic map with
      3,568 SNP markers. As a fine-mapping approach, chromosome-wide association
      mapping targeting a QTL hot-spot on linkage group XIV was performed in the two P.
      trichocarpa populations. Both populations were genotyped using the 34 K Populus
      Infinium SNP array and whole-genome resequencing of one of the populations
      facilitated marker-saturation of candidate intervals for gene identification.
      RESULTS: Five QTLs ranging in size from 0.6 to 1.8 Mb were mapped on linkage
      group XIV for lignin content, syringyl to guaiacyl (S/G) ratio, 5- and 6-carbon
      sugars using the mapping pedigree. Six candidate loci exhibiting significant
      associations with phenotypes were identified within QTL intervals. These
      associations were reproducible across multiple environments, two independent
      genotyping platforms, and different plant growth stages. cDNA sequencing for
      allelic variants of three of the six loci identified polymorphisms leading to
      variable length poly glutamine (PolyQ) stretch in a transcription factor
      annotated as an ANGUSTIFOLIA C-terminus Binding Protein (CtBP) and premature stop
      codons in a KANADI transcription factor as well as a protein kinase. Results from
      protoplast transient expression assays suggested that each of the polymorphisms
      conferred allelic differences in the activation of cellulose, hemicelluloses, and
      lignin pathway marker genes. CONCLUSION: This study illustrates the utility of
      complementary QTL and association mapping as tools for gene discovery with no a
      priori candidate gene selection. This proof of concept in a perennial organism
      opens up opportunities for discovery of novel genetic determinants of
      economically important but complex traits in plants.

PMID- 25613059
TI  - Supramolecular nanosubstrate-mediated delivery for reprogramming and
      transdifferentiation of mammalian cells.
AB  - Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of
      molecular self-assembly and a nanostructured substrate platform for the low
      toxicity, highly efficient co-delivery of biological factors encapsulated in a
      nanovector. Human fibroblasts are successfully reprogrammed into induced
      pluripotent stems and transdifferentiated into induced neuronal-like cells. 

PMID- 25613060
TI  - Adipose-derived stem cell sheet transplantation therapy in a porcine model of
      chronic heart failure.
AB  - Adipose-derived stem cells (ASCs) are a promising resource for cell
      transplantation therapy for damaged heart tissue. Cell death in the graft early
      after transplantation represents the main cause of unsatisfactory therapeutic
      efficacy, but tissue-engineered cell sheets grown in temperature-responsive cell
      culture dishes may enable improved engraftment of transplanted cells. We
      investigated the therapeutic potential of this method in chronic myocardial
      ischemia in swine. We created a porcine model of chronic heart failure by
      implanting an ameroid constrictor around the main trunk of the left anterior
      descending artery, just distal to the circumflex branch. Simultaneously, ASCs
      were obtained from a piece of subcutaneous adipose tissue and expanded to form
      ASC sheets using temperature-responsive dishes. Four weeks after ameroid
      constrictor placement, triple-layered ASC sheets were transplanted onto the area
      of the ischemic myocardium (sheet group, n = 7). Controls (n = 7) received no
      sheet. Just before and 4 weeks after transplantation, left ventriculography (LVG)
      and coronary angiography (CAG) were performed. LVG revealed a significant
      improvement in the left ventricular ejection fraction of the sheet group compared
      with controls (47.6 +/- 2.9% vs 41.4 +/- 2.8%, P < 0.05). Furthermore,
      development of collateral vessels was only detected in the sheet group with right
      CAG. Histologic analysis demonstrated that engrafted ASC sheets grew to form a
      thickened layer that included newly formed vessels. ASC sheet transplantation
      therapy is an intriguing therapeutic method for ischemic heart failure. 

PMID- 25613061
TI  - Mesolimbic dopaminergic dysfunction in Parkinson's disease depression: evidence
      from a 123I-FP-CIT SPECT investigation.
AB  - We investigated the striatal and extrastriatal DAT availability (SPM8) by
      [(123)I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without
      depression. A cluster with significant (p < 0.05) lower tracer binding in PD with
      depression was found in left cingulate cortex, persistent after correction for
      age, disease severity and duration, and inversely correlated with depression
      scores (r -0.336, p < 0.05). Our data indicate a significant association between
      PD depression and cingulate dopaminergic denervation supporting the dopaminergic
      hypothesis of PD depression.

PMID- 25613062
TI  - Activation of alpha7 nicotinic acetylcholine receptors prevents monosodium
      iodoacetate-induced osteoarthritis in rats.
AB  - BACKGROUND/AIMS: Although some evidence suggests that the prevalence of
      osteoarthritis (OA) is lower in smokers compared to nonsmokers, the mechanisms of
      nicotine-induced protection remain unclear. Stimulation of the alpha7 nicotinic
      acetylcholine receptor (alpha7-nAChR) appears to be a critical mechanism
      underlying the anti-inflammatory potential of cholinergic agonists in immune
      cells. The inhibition of secreted inflammatory molecules and the subsequent
      inflammatory processes have been proposed as a novel strategy for the treatment
      of OA. The objective of the present study was to determine whether nicotine
      induced protection in a monosodium iodoacetate (MIA) rat model of OA occurs via
      alpha7-nAChR-mediated inhibition of chondrocytes. METHODS: Both in vivo (MIA) and
      in vitro (MIA; Interleukin-1beta, IL-1beta) models of OA were used to investigate
      the roles and the possible mechanisms whereby alpha7-nAChRs protect against knee
      joint degradation. Multiple experimental approaches, including macroscopic,
      histological analysis, chondrocyte cell cultures, confocal microscopy, and
      western blotting, were employed to elucidate the mechanisms of alpha7-nAChR
      mediated protection. RESULTS: Systemic administration of nicotine alleviated MIA
      induced joint degradation. The protective effects of nicotine were abolished by
      administration of the alpha7-nAChR-selective antagonist methyllycaconitine (MLA).
      In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both
      p38, extracellular regulated kinase (Erk) 1/2 and c-Jun-N-terminal kinase (JNK)
      mitogen-activated protein kinases (MAPK) phosphorylation and phosphorylated
      nuclear factor-kappa B (NF-kappaB) p65 activation induced by MIA- or IL-1beta,
      and these effects were also reversed by MLA. CONCLUSION: Taken together, our
      results suggest that activation alpha7-nAChRs is an important mechanism
      underlying the protective effects of nicotine.

PMID- 25613063
TI  - ARNT2 is downregulated and serves as a potential tumor suppressor gene in non
      small cell lung cancer.
AB  - The present study aims to investigate the expression pattern of aryl hydrocarbon
      receptor nuclear translocator 2 (ARNT2) protein and its clinical significance in
      human non-small cell lung cancer (NSCLC). We investigated the expression levels
      of ARNT2 in 104 NSCLC surgical specimens by immunohistochemistry and then
      analyzed its clinical significance. Additionally, the role of ARNT2 on the
      biological properties of the NSCLC line HCC827 was experimentally tested in vitro
      and in vivo to confirm the clinical observations. We found that the expression
      level of ARNT2 was significantly higher in normal lung tissues compared with
      NSCLC tissues (P < 0.01). Overall survival (OS) of patients with a high
      intratumoral ARNT2 level was significantly longer than survival of those with a
      low ARNT2 level (P = 0.004). In addition, intratumoral ARNT2 expression was an
      independent prognostic factors for OS (hazard ratio [HR] = 0.529; P = 0.001). 3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed
      that the ARNT2 overexpression inhibited cell viability, while ARNT2 knockdown
      promoted cell growth in NSCLC cell lines HCC827 and A549. Annexin V/PI assay
      showed that ARNT2 overexpression increased cell apoptosis, while ARNT2 knockdown
      decreased cell apoptosis in HCC827 and A549 cells. Moreover, in vivo study showed
      that attenuated ARNT2 expression in HCC827 cells greatly promoted tumor growth,
      while overexpressed ARNT2 remarkably inhibited tumor growth in a HCC827 xenograft
      model. Taken together, our data demonstrate that ARNT2 might serve as a tumor
      suppressor in NSCLC progression.

PMID- 25613064
TI  - Serum IL-17F combined with VEGF as potential diagnostic biomarkers for oral
      squamous cell carcinoma.
AB  - Although interleukin (IL) 17A can promote angiogenesis in several tumors, there
      are limited clinical evidences on cancer about the correlation between serum
      vascular endothelial growth factor (VEGF) and IL-17F, which is the most
      homologous to IL-17A. In this study, serum concentration of IL-17F and VEGF from
      healthy (n = 28), leukoplakia (n = 15), and oral squamous cell carcinoma (OSCC)
      groups (n = 85) were assessed and showed that IL-17F level was remarkably
      downregulated from healthy group (394.3 pg/ml) to OSCC group (82.96 pg/ml).
      Conversely, the OSCC group had a highest level of VEGF (P < 0.05) in whole
      groups, and there was a negative correlation between IL-17F and VEGF in serum or
      in the peripheral blood mononuclear cells (PBMCs) at mRNA level. Moreover, the
      lowest ratio of IL-17F/VEGF was found in OSCC patients (P < 0.05) and lower ratio
      of IL-17F/VEGF correlated to higher tumor stage and lymph node metastasis.
      Furthermore, the serum level of IL-17F and the ratio of IL-17F/VEGF were
      positively associated with the numbers of CD3(+) CD4(+) T cells, which indicated
      that serum IL-17F could originate from PBMCs during the development of OSCC, and
      could be used for the diagnosis by effectively distinguishing OSCC patients from
      healthy individuals. 

PMID- 25613065
TI  - Preliminary screening of differentially expressed genes involved in methyl-CpG
      binding protein 2 gene-mediated proliferation in human osteosarcoma cells.
AB  - Methyl-CpG-binding protein 2 (MeCP2) is essential in human brain development and
      has been linked to several cancer types and neuro-developmental disorders. This
      study aims to screen the MeCP2 related differentially expressed genes and
      discover the therapeutic targets for osteosarcoma. CCK8 assay was used to detect
      the proliferation and SaOS2 and U2OS cells. Apoptosis of cells was detected by
      flow cytometry analysis that monitored Annexin V-APC/7-DD binding and 7-ADD
      uptake simultaneously. Denaturing formaldehyde agarose gel electrophoresis was
      employed to examine the quality of total RNA 18S and 28S units. Gene chip
      technique was utilized to discover the differentially expressed genes correlated
      with MeCP2 gene. Differential gene screening criteria were used to screen the
      changed genes. The gene up-regulation or down-regulation more than 1.5 times was
      regarded as significant differential expression genes. The CCK8 results indicated
      that the cell proliferation of MeCP2 silencing cells (LV-MeCP2-RNAi) was
      significantly decreased compared to non-silenced cells (LV-MeCP2-RNAi-CN) (P <
      0.05). MeCP2 silencing could also induce significant apoptosis compared to non
      silenced cells (P < 0.05); 107 expression changed genes were screened from a
      total of 49,395 transcripts. Among the total 107 transcripts, 34 transcripts were
      up-regulated and 73 transcripts were down-regulated. There were five significant
      differentially expressed genes, including IGFBP4, HOXC8, LMO4, MDK, and CTGF,
      which correlated with the MeCP2 gene. The methylation frequency of CpG in IGFBP4
      gene could achieve 55%. In conclusion, the differentially expressed IGFBP4,
      HOXC8, LMO4, MDK, and CTGF genes may be involved in MeCP2 gene-mediated
      proliferation and apoptosis in osteosarcoma cells.

PMID- 25613066
TI  - Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis
      in glioma.
AB  - The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a bona
      fide long noncoding RNA (lncRNA). LncRNA MALAT1 was discovered as a prognostic
      factor for lung cancer metastasis but also has been linked to several other human
      tumor entities. However, little is known about the role of lncRNA MALAT1 in
      glioma patients. The aim of this study was to identify the role of lncRNA MALAT1
      in the pathogenesis of glioma; we analyzed the relationship of lncRNA MALAT1
      expression with clinicopathological characteristics in glioma patients. In our
      results, lncRNA MALAT1 expression was increased in glioma tissues compared with
      paired adjacent brain normal tissues (P < 0.001). Furthermore, lncRNA MALAT1 was
      associated significantly with WHO grade (I-II vs. III-IV; P = 0.007) and tumor
      size (< 3 cm vs. T >= 3 cm; P = 0.008). However, lncRNA MALAT1 expression was not
      associated significantly with age (<45 vs. >= 45, P = 0.343), gender (female vs.
      male, P = 0.196), family history of cancer (yes vs. no, P = 0.665), and tumor
      location (supratentorial vs. infratentorial, P = 0.170). Moreover, the level of
      lncRNA MALAT1 expression was markedly correlated with the glioma patients'
      overall survival (P < 0.001). Multivariate analysis suggested that increased
      lncRNA MALAT1 expression was a poor independent prognostic predictor for glioma
      patients (P = 0.002). In conclusion, lncRNA MALAT1 plays an important role on
      glioma progression and prognosis and may serve as a convictive prognostic
      biomarker for glioma patients.

PMID- 25613067
TI  - Cancer-associated fibroblasts promote renal cell carcinoma progression.
AB  - The aim of this study was to determine the effect of cancer-associated
      fibroblasts (CAFs) on renal cell carcinoma (RCC) tumor proliferation, migration,
      and development of drug resistance, thus underlying their potential as
      therapeutic targets in RCC patients. CAFs were grown in primary cultures. The in
      vitro model of interaction of RCC cell lines with CAFs was established. The
      influence of CAFs on the proliferation and migration ability as well as
      sensitivity to everolimus of RCC cells was further analyzed. Furthermore, Western
      blotting analysis was performed to examine the mechanisms mediating the effect of
      CAFs on RCC cells. The results of the MTT assay showed that coculture with CAFs
      increased the proliferation activity of both 786-O and Caki-1 cells compared with
      serum-free medium controls. The migration ability of RCC cell lines was also
      significantly enhanced after coculture treatment compared with untreated control.
      The inhibition effect of everolimus on 786-O and Caki-1 cells abrogated in
      cocultures with CAFs. The sensitivity of both two cell lines to everolimus was
      dramatically decreased when cocultured with CAFs. RCC cells cocultured with CAFs
      resulted in the activation of both proliferation-related (Erks) and survival
      related (Akt) pathways. These data indicate that CAFs have an important role in
      supporting and promoting RCC. The interaction of CAFs with RCC cell lines
      stimulates tumor cell proliferation and migration and induces resistance to
      everolimus in RCC cells, suggesting that target of the tumor microenvironment may
      be a novel targeted therapies for RCC. 

PMID- 25613068
TI  - Involvement of acid-sensing ion channel 1alpha in hepatic carcinoma cell
      migration and invasion.
AB  - An acidic microenvironment promotes carcinoma cell proliferation and migration.
      Acid-sensing ion channels (ASICs) are H(+), Ca(2+), and Na(+)-gated cation
      channels that are activated by changes in the extracellular pH, and ASIC1alpha
      may be associated with tumor proliferation and migration. Here, we investigated
      the role of ASIC1alpha in hepatocellular carcinoma (HCC) migration and invasion.
      The expression of ASIC1alpha was examined in 15 paired HCC and adjacent non-tumor
      tissues by immunohistochemistry. Reverse transcription (RT)-PCR and Western
      blotting were used to assess ASIC1alpha messenger RNA (mRNA) and protein
      expression in the HCC cell line SMMC-7721 cultured in different pH media or
      transfected with short hairpin RNA (shRNA) against ASIC1alpha. Cell migration
      ability was detected by wound healing and Transwell assays. ASIC1alpha expression
      was significantly higher in tumor tissues than in non-tumor tissues, and it was
      higher in HCC with postoperative metastasis than in that without metastasis.
      ASIC1alpha mRNA and protein expression was significantly higher in SMMC-7721
      cells cultured at pH 6.5 than in those cultured at pH 7.4 and 6.0. shRNA-mediated
      silencing of ASIC1alpha significantly downregulated ASIC1alpha mRNA and protein
      expression compared with negative control or untransfected cells and inhibited
      HCC cell migration and invasion. ASIC1alpha is overexpressed in HCC tissues and
      associated with advanced clinical stage. A moderately acidic extracellular
      environment promoted ASIC1alpha expression, and silencing of ASIC1alpha
      expression inhibited the migration and invasion of HCC cells. Suppression of
      ASIC1alpha expression by RNAi attenuated the malignant phenotype of HCC cells,
      suggesting a novel approach for anticancer gene therapy.

PMID- 25613069
TI  - Associations of polymorphisms in microRNAs with female breast cancer risk in
      Chinese population.
AB  - Polymorphisms in microRNA (miRNA) have been discussed to be associated with
      breast cancer risk; however, the conclusions were always inconsistent in
      different ethnicities. This case-control study enrolled 450 breast cancer cases,
      and 450 health controls was carried out to investigate the association between
      six polymorphisms in miRNAs and breast cancer risk. Sequenom MassARRAY was used
      to detect the polymorphisms in miRNAs, and the immunohistochemistry assay was
      applied to detect the expression of estrogen receptor (ER) and progesterone
      receptor (PR) in cancer tissue. The data showed that the 3746444 GG was
      associated with increased breast cancer risk (adjusted odds ratio (OR) = 1.71, 95
      % confidence interval (CI) = 1.16-2.52) and that rs2292832 CC (adjusted OR =
      0.54, 95 % CI = 0.34-0.85) was associated with decreased breast cancer risk. In
      addition, menopausal status subgroup analysis revealed that rs3746444 GG
      (adjusted OR = 2.34, 95 % CI = 1.31-4.15) and GA/GG (adjusted OR = 1.60, 95 % CI
      = 1.08-2.37) genotypes were associated with increased breast cancer risk for the
      subgroup of women with premenopausal status, respectively. Moreover, rs2910164 GG
      (adjusted OR = 1.84, 95 % CI = 1.07-3.15) and CG/GG (adjusted OR = 1.47, 95 % CI
      = 1.01-2.15) genotypes were associated with increased breast cancer risk in the
      postmenopausal status subcohort, respectively. Furthermore, rs3746444 AG
      (adjusted OR = 1.61, 95 % CI = 1.06-2.45) and AG/GG (adjusted OR = 1.49, 95 % CI
      = 1.02-2.18) genotypes were observed to be associated with increased risk of
      lymph node involvement and breast cancer with negative PR expression, separately.
      In short, rs3746444 was associated with breast cancer risk, especially for women
      with premenopausal status, and rs2910164 CG and CG/GG genotypes were associated
      with breast cancer risk for the women with premenopausal status.

PMID- 25613070
TI  - Epigenetic inactivation of SOX1 promotes cell migration in lung cancer.
AB  - SOX1 is epigenetically inactivated in hepatocellular carcinoma. However, the
      expression and methylation status of SOX1 in non-small cell lung cancer (NSCLC)
      remains unknown. The aim of the current study was to investigate whether the
      promoter hypermethylation of SOX1 is involved in human lung carcinogenesis. We
      first detected the expression of SOX1 protein in a tissue microarray (TMA) of
      primary NSCLC and adjacent normal lung tissue specimens using immunohistochemical
      staining with a specific anti-SOX1 antibody. Methylation of the promoter region
      of SOX1 in lung cancer tissues was determined by bisulfite sequencing PCR (BSP).
      In the present study, we found that the SOX1 promoter was fully or partially
      methylated in 40 of 60 (66.7 %) tumor tissues but not in the majority 15 of 60
      (25 %) of normal tissues. A statistically significant inverse association was
      found between SOX1 methylation status and expression of the SOX1 in tumor tissues
      (P = 0.003). We further demonstrate that restoration of SOX1 inhibited cell
      migration by regulating actin cytoskeletal remodeling. Our results suggest that
      SOX1 is epigenetically silenced in the majority of NSCLC and restoration of SOX1
      inhibited cell migration by regulating actin cytoskeletal remodeling in NSCLC.

PMID- 25613071
TI  - A novel tumor suppressor gene in basal cell carcinoma: inhibition of growth
      factor-2.
AB  - In loss of heterozygosity (LOH) studies at the chromosome 4q22-35 region, it was
      shown that the amount of deletion was high in basal cell carcinoma (BCC). It has
      been proposed that genes located in this chromosomal region could be tumor
      suppressor genes in BCC. It has been thought that deletions in the ING2 gene
      located in the same region can play a role in the pathophysiology of BCC and that
      deletions occurring in this region may influence the level of ING2 expression in
      BCC. Tumoral and non-tumoral tissues from 75 patients with BCC (45 men and 30
      women) were included to the study. Lesions were excised by a surgical margin of
      0.5 cm. After excision, RNA was isolated from tumoral and non-tumoral tissue
      samples. ING2 messenger RNA (mRNA) expression level was determined in tumoral and
      non-tumoral tissues by the real-time polymerase chain reaction (RT-PCR). It was
      detected that ING2 mRNA expression level decreased in tumoral tissues when
      compared to non-tumoral tissues from BCC patients (p = 0.0001). It was found that
      expression levels of this gene were comparable among patients with primary,
      recurrent, or multiple BCC. It is thought that ING2 gene expression level could
      contribute to the development of BCC but not be associated with the stage and the
      prognosis of the tumor.

PMID- 25613073
TI  - Mitochondrial DNA copy number, but not haplogroup is associated with keratoconus
      in Han Chinese population.
AB  - Oxidative stress may play a role in the pathogenesis of keratoconus (KC).
      Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and
      variations may affect the generation of reactive oxygen species (ROS) and be
      involved in the pathogenesis of KC. To test whether mtDNA background and copy
      number confer genetic susceptibility to KC in the Han Chinese population, we
      performed this association study. We analyzed mtDNA sequence variations in 210 KC
      patients and 309 matched individuals from China, and classified each subject by
      haplogroup. Mitochondrial DNA copy number was measured in a subset of these
      subjects (193 patients and 103 controls). Comparison of matrilineal components of
      the cases and control populations revealed no significant difference. However,
      measurement of mtDNA copy number showed that KC patients had significantly lower
      mtDNA copy numbers than controls (P = 0.0002), even when age, gender, and mtDNA
      background were considered. Our results suggest that mtDNA copy number, but not
      haplogroup, is associated with keratoconus, and may contribute to its
      pathogenesis. 

PMID- 25613072
TI  - Corneal stroma microfibrils.
AB  - Elastic tissue was first described well over a hundred years ago and has since
      been identified in nearly every part of the body. In this review, we examine
      elastic tissue in the corneal stroma with some mention of other ocular structures
      which have been more thoroughly described in the past. True elastic fibers
      consist of an elastin core surrounded by fibrillin microfibrils. However, the
      presence of elastin fibers is not a requirement and some elastic tissue is
      comprised of non-elastin-containing bundles of microfibrils. Fibers containing a
      higher relative amount of elastin are associated with greater elasticity and
      those without elastin, with structural support. Recently it has been shown that
      the microfibrils, not only serve mechanical roles, but are also involved in cell
      signaling through force transduction and the release of TGF-beta. A well
      characterized example of elastin-free microfibril bundles (EFMBs) is found in the
      ciliary zonules which suspend the crystalline lens in the eye. Through
      contraction of the ciliary muscle they exert enough force to reshape the lens and
      thereby change its focal point. It is believed that the molecules comprising
      these fibers do not turn-over and yet retain their tensile strength for the life
      of the animal. The mechanical properties of the cornea (strength, elasticity,
      resiliency) would suggest that EFMBs are present there as well. However, many
      authors have reported that, although present during embryonic and early postnatal
      development, EFMBs are generally not present in adults. Serial-block-face imaging
      with a scanning electron microscope enabled 3D reconstruction of elements in
      murine corneas. Among these elements were found fibers that formed an extensive
      network throughout the cornea. In single sections these fibers appeared as
      electron dense patches. Transmission electron microscopy provided additional
      detail of these patches and showed them to be composed of fibrils (~10 nm
      diameter). Immunogold evidence clearly identified these fibrils as fibrillin
      EFMBs and EFMBs were also observed with TEM (without immunogold) in adult mammals
      of several species. Evidence of the presence of EFMBs in adult corneas will
      hopefully pique an interest in further studies that will ultimately improve our
      understanding of the cornea's biomechanical properties and its capacity to
      repair. 

PMID- 25613075
TI  - High-Resolution Array Comparative Genomic Hybridization Utility in Polish
      Newborns with Isolated Cleft Lip and Palate.
AB  - Cleft lip with or without cleft palate is one of the most common birth defects of
      unknown etiology. A fraction of its genetic causes is attributable to copy number
      variations detected by array comparative genomic hybridization. The value of
      array comparative genomic hybridization screening as a first-tier test in the
      newborn population with multiple congenital anomalies has now been accepted. Due
      to unspecific clinical picture at this age, it can also be applied to neonates
      with isolated anomalies. Our purpose was to assess utility of array comparative
      genomic hybridization in the population of newborns with isolated cleft lip and
      palate. We conducted the study in a group of 52 Polish newborns with apparently
      isolated cleft lip and palate. In the study group, we found 8 rearrangements. Of
      these, 2 de novo events have been noted that potentially explain the phenotype.
      In addition, 2 novel candidate genes for cleft lip and palate, CHN2 and CDH19,
      are suggested. Given the high number of inherited potentially benign changes, we
      question the clinical utility of array comparative genomic hybridization in the
      newborn population with isolated cleft lip and palate, at the same time pointing
      to the need of skilled professional's clinical assessment at a later age.
      However, the value of this technology in searching for the cause of isolated
      anomalies cannot be underestimated.

PMID- 25613074
TI  - Construction of a human corneal stromal equivalent with non-transfected human
      corneal stromal cells and acellular porcine corneal stromata.
AB  - A tissue-engineered human corneal stroma (TE-HCS) has been developed as a
      promising equivalent to the native corneal stroma for replacement therapy.
      However, there is still a crucial need to improve the current approaches to
      render the TE-HCS equivalent more favorable for clinical applications. At the
      present study, we constructed a TE-HCS by incubating non-transfected human
      corneal stromal (HCS) cells in an acellular porcine corneal stromata (aPCS)
      scaffold in 20% fetal bovine serum supplemented DMEM/F12 (1:1) medium at 37 
      degrees C with 5% CO2in vitro. After 3 days of incubation, the constructed TE-HCS
      had a suitable tensile strength for transplantation, and a transparency that is
      comparable to native cornea. The TE-HCS had a normal histological structure which
      contained regularly aligned collagen fibers and differentiated HCS cells with
      positive expression of marker and functional proteins, mimicking a native HCS.
      After transplantation into rabbit models, the TE-HCS reconstructed normal corneal
      stroma in vivo and function well in maintaining corneal clarity and thickness,
      indicating that the completely biological TE-HCS could be used as a HCS
      equivalent. The constructed TE-HCS has promising potentials in regenerative
      medicine and treatment of diseases caused by corneal stromal disorders. 

PMID- 25613076
TI  - Pressure on NHS hospitals is "spreading beyond emergency departments," King's
      Fund warns.

PMID- 25613077
TI  - Intra-population trends in the maturation and reproduction of a temperate marine
      herbivore Girella elevata across latitudinal clines.
AB  - Latitudinal variation in the reproductive characteristics of a temperate marine
      herbivore, rock blackfish Girella elevata, was examined from three regions of the
      south-eastern Australian coast. Biological sampling covered 780 km of coastline,
      including the majority of the species distribution. The sampling range
      incorporated three distinct oceanographic regions of the East Australian Current,
      a poleward-flowing western boundary current of the Southern Pacific Gyre and
      climate-change hotspot. Girella elevata are a highly fecund, group synchronous
      (multiple batch)-spawner. Mean fork length (LF ) and age at maturity were greater
      for females than males within all regions, with both male and female G. elevata
      of the southern region maturing at a greater size and age than those from the
      central region. Estimates of batch fecundity (FB ) were greatest in the northern
      and southern regions, relative to the central region where growth rates were
      greatest. Significant positive relationships were observed between FB and LF ,
      and FB and total fish mass. Gonado-somatic indices indicated latitudinal
      synchrony in spawning seasonality between G. elevata at higher latitudes,
      spawning in the late austral spring and summer. A late or prolonged spawning
      period is evident for G. elevata from the northern region. Juvenile recruitment
      to intertidal rock pools within the central and southern regions was synchronous
      with the spawning season, however, no juveniles were found within the northern
      region. The implications of latitudinal variation in reproductive characteristics
      are discussed in the context of climate and oceanographic conditions of south
      east Australia.

PMID- 25613078
TI  - Cross-sectional survey of antibiotic resistance in Escherichia coli isolated from
      diseased farm livestock in England and Wales.
AB  - Between 2005 and 2007, E. coli obtained from clinical diagnostic submissions from
      cattle, goats, pigs and sheep to government laboratories in England and Wales
      were tested for sensitivity to 16 antimicrobials. Resistance was most commonly
      observed against ampicillin, streptomycin, sulphonamides and tetracyclines.
      Resistance levels varied significantly between species, with isolates from cattle
      frequently showing the highest levels. Verocytotoxigenic E. coli (VTEC) expressed
      less resistance than non-VTEC. Only 19.3% of non-VTEC and 43.5% of VTEC were
      susceptible to all antimicrobials, while 47.1% and 30.4%, respectively, were
      resistant to ?5 antimicrobials. The resistance phenotype SSuT was commonly
      observed, and isolates resistant to third-generation cephalosporins were also
      identified. We recommend judicious antimicrobial usage in the livestock industry
      in order to preserve efficacy. 

PMID- 25613080
TI  - Identification of diabetes, heart disease, hypertension and stroke in mid- and
      older-aged women: Comparing self-report and administrative hospital data records.
AB  - AIM: To estimate the prevalence of diabetes, heart disease, hypertension and
      stroke in self-report and hospital data in two cohorts of women; measure
      sensitivity and agreement between data sources; and compare between cohorts.
      METHODS: Women born between 1946-1951 and 1921-1926 who participated in the
      Australian Longitudinal Study on Women's Health (ALSWH); were New South Wales
      residents; and admitted to hospital (2004-2008) were included in the present
      study. The prevalence of diabetes, heart disease, hypertension and stroke was
      estimated using self-report (case 1 at latest survey, case 2 across multiple
      surveys) and hospital records. Agreement (kappa) and sensitivity (%) were
      calculated. Logistic regression measured the association between patient
      characteristics and agreement. RESULTS: Hypertension had the highest prevalence
      and estimates were higher for older women: 32.5% case 1, 45.4% case 2, 12.8% in
      hospital data (1946-1951 cohort); 57.8% case 1, 73.2% case 2, 38.2% in hospital
      data (1921-1926 cohort). Agreement was substantial for diabetes: kappa = 0.75
      case 1, kappa = 0.70 case 2 (1946-1951 cohort); kappa = 0.77 case 1, kappa = 0.80
      case 2 (1921-1926 cohort), and lower for other conditions. The 1946-1951 cohort
      had 2.08 times the odds of agreement for hypertension (95% CI 1.56 to 2.78; P <
      0.0001), and 6.25 times the odds of agreement for heart disease (95% CI 4.35 to
      10.0; P < 0.0001), compared with the 1921-1926 cohort. CONCLUSION: Substantial
      agreement was found for diabetes, indicating accuracy of ascertainment using self
      report or hospital data. Self-report data appears to be less accurate for heart
      disease and stroke. Hypertension was underestimated in hospital data. These
      findings have implications for epidemiological studies relying on self-report or
      administrative data.

PMID- 25613079
TI  - Different forms of effective connectivity in primate frontotemporal pathways.
AB  - It is generally held that non-primary sensory regions of the brain have a strong
      impact on frontal cortex. However, the effective connectivity of pathways to
      frontal cortex is poorly understood. Here we microstimulate sites in the superior
      temporal and ventral frontal cortex of monkeys and use functional magnetic
      resonance imaging to evaluate the functional activity resulting from the
      stimulation of interconnected regions. Surprisingly, we find that, although
      certain earlier stages of auditory cortical processing can strongly activate
      frontal cortex, downstream auditory regions, such as voice-sensitive cortex,
      appear to functionally engage primarily an ipsilateral temporal lobe network.
      Stimulating other sites within this activated temporal lobe network shows strong
      activation of frontal cortex. The results indicate that the relative stage of
      sensory processing does not predict the level of functional access to the frontal
      lobes. Rather, certain brain regions engage local networks, only parts of which
      have a strong functional impact on frontal cortex. 

PMID- 25613081
TI  - Assessing the discriminant ability, reliability, and comparability of multiple
      short forms of the Boston Naming Test in an Alzheimer's disease center cohort.
AB  - BACKGROUND: The Boston Naming Test (BNT) is a commonly used neuropsychological
      test of confrontation naming that aids in determining the presence and severity
      of dysnomia. Many short versions of the original 60-item test have been developed
      and are routinely administered in clinical/research settings. Because of the
      common need to translate similar measures within and across studies, it is
      important to evaluate the operating characteristics and agreement of different
      BNT versions. METHODS: We analyzed longitudinal data of research volunteers (n =
      681) from the University of Kentucky Alzheimer's Disease Center longitudinal
      cohort. CONCLUSIONS: With the notable exception of the Consortium to Establish a
      Registry for Alzheimer's Disease (CERAD) 15-item BNT, short forms were internally
      consistent and highly correlated with the full version; these measures varied by
      diagnosis and generally improved from normal to mild cognitive impairment (MCI)
      to dementia. All short forms retained the ability to discriminate between normal
      subjects and those with dementia. The ability to discriminate between normal and
      MCI subjects was less strong for the short forms than the full BNT, but they
      exhibited similar patterns. These results have important implications for
      researchers designing longitudinal studies, who must consider that the
      statistical properties of even closely related test forms may be quite different.

PMID- 25613082
TI  - Normal or abnormal? 'Normative uncertainty' in psychiatric practice.
AB  - The 'multicultural clinical interaction' presents itself as a dilemma for the
      mental health practitioner. Literature describes two problematic areas where this
      issues emerges--how to make an adequate distinction between religious rituals and
      the rituals that may be symptomatic of 'obsessive compulsive disorder' (OCD), and
      how to differentiate 'normative' religious or spiritual beliefs, behaviours, and
      experiences from 'psychotic' illnesses. When it comes to understanding service
      user's 'idioms of distress', beliefs about how culture influences behaviour can
      create considerable confusion and 'normative uncertainty' for mental health
      practitioners. In the absence of clear diagnostic and assessment criteria on
      distinguishing between 'culture' and 'psychopathology', practitioners have had to
      rely on their own intuition and seek out possible 'strategies' or 'procedures'
      from a contradictory and cross-disciplinary evidence base. Decontextualisation of
      service users' experiences may result in the pathologisation of culturally
      'normative' phenomenon, 'category fallacy' errors, and poor health care
      experiences and outcomes for service users.This paper situates this dilemma
      within a wider debate that has concerned both the biomedical and social sciences,
      namely, the unresolved question of 'normality' or 'abnormality'. Indeed, issues
      that arise from dilemmas surrounding the question of 'culture' or
      'psychopathology' are intimately tied to wider cultural ideas about what is
      considered 'normal'. The disciplines of psychiatry, psychology, and medical
      anthropology have struggled to establish workable criteria against which to judge
      behaviour as 'normal', 'abnormal', or 'pathological'. Three models for
      understanding mental 'abnormality' are evident in 'transcultural psychiatry'
      (what is now commonly known as 'cultural psychiatry'), and these models have
      corresponded closely to the interpretive models used by anthropologists
      attempting to make sense of the apparent diversity of human societies. The three
      models of 'absolutism', 'universalism' and 'cultural relativism' have not only
      important consequences for the nature and conduct of research enquiry, but also
      have implications for how the dilemma of 'culture' or 'psychopathology' is
      attended to in clinical practice.

PMID- 25613083
TI  - Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma.
AB  - PURPOSE: Few treatment options are available for patients with advanced or
      metastatic hepatocellular carcinoma (HCC). Based on preclinical and early
      clinical efficacy signals and lack of overlapping toxicity, we undertook this
      multicenter phase II trial to estimate efficacy and safety of everolimus and
      pasireotide in advanced HCC. METHODS: Patients with advanced HCC not amenable to
      locoregional therapy and Child-Pugh A cirrhosis received everolimus 7.5 mg PO
      daily and pasireotide LAR 60 mg IM every 28 days. The primary endpoint was time
      to progression (TTP), with 26 events needed to evaluate if everolimus +
      pasireotide improved TTP from 2.8 to 4.4 months, with 80% power and an alpha of
      0.05. Secondary endpoints included response as measured by RECIST modified for
      HCC, treatment-emergent adverse events, and overall survival. RESULTS: After 24
      patients were enrolled, results of a randomized trial showing no benefit of
      everolimus in HCC were released prompting an unplanned interim analysis that
      found the conditional probability of rejecting the null hypothesis based on
      events in those patients was 0.08. Therefore accrual was halted. Patients had a
      median age of 59 years, 21 (88%) had BCLC stage C cancer, and 11 (46%) metastatic
      disease. Median TTP was 3.5 months (95% CI 2-5.8) and median survival 6.7 months
      (95% CI 6-infinity). Best response was stable disease in ten patients. Grade 3
      hyperglycemia occurred in 6 (25%). There were no grade 4 treatment-emergent
      events. CONCLUSION: Despite promising early efficacy signals, we found no benefit
      for the combination of everolimus and pasireotide in HCC.

PMID- 25613084
TI  - Pertussis in the newborn: certainties and uncertainties in 2014.
AB  - Bordetella pertussis infection remains a serious potential health risk to
      infants, specially in those too young to be vaccinated. Over the recent years,
      numerous sources highlighted a widespread resurgence, making it, again, a
      challenging disease. Globally, pertussis is ranked among the 10 leading causes of
      childhood mortality. This review summarizes the most recent literature and will
      address the most important aspects that pediatricians and neonatologists must be
      familiar with, when treating a newborns pertussis infection. 

PMID- 25613085
TI  - Molecular detection of infectious bronchitis and avian metapneumoviruses in Oman
      backyard poultry.
AB  - Infectious bronchitis virus (IBV) and avian metapneumovirus (aMPV) are
      economically important viral pathogens infecting chickens globally.
      Identification of endemic IBV and aMPV strains promotes better control of both
      diseases and prevents production losses. Orophrayngeal swab samples were taken
      from 2317 birds within 243 different backyard flocks in Oman. Swabs from each
      flock were examined by RT-PCR using part-S1 and G gene primers for IBV and aMPV
      respectively. Thirty-nine chicken flocks were positive for IBV. Thirty two of
      these were genotyped and they were closely related to 793/B, M41, D274,
      IS/1494/06 and IS/885/00. 793/B-like IBV was also found in one turkey and one
      duck flock. Five flocks were positive for aMPV subtype B. Though no disease was
      witnessed at the time of sampling, identified viruses including variant IBV
      strains, may still pose a threat for both backyard and commercial poultry in
      Oman. 

PMID- 25613086
TI  - Pregnancy-associated glycoprotein (PAG) concentration in plasma and milk samples
      for early pregnancy diagnosis in Lacaune dairy sheep.
AB  - In the present study, four RIA systems (RIA-1 to -4) based on two antisera raised
      against ovine pregnancy-associated glycoproteins (ovPAGs), combined with an ovine
      or a bovine PAG tracer were used to measure PAG concentrations in plasma and milk
      samples of dairy ewes. Blood and milk samples were collected on different days of
      gestation: 0, 18, 20, 22, 25, 28, 32, 42, and 49. From day 20 onward, the PAG in
      plasma could be detected in all pregnant ewes using the four RIA systems. By
      using milk, except for RIA-1, the other systems showed a sensitivity of 100% from
      day 28 of gestation onward. In plasma, PAG concentrations were higher in multiple
      than in single pregnancies, while no clear relationship was observed in milk. In
      conclusion, milk is a good alternative to plasma for early pregnancy diagnosis in
      sheep from day 28 to day 42. 

PMID- 25613087
TI  - Assessment of the impact of photosystem I chlorophyll fluorescence on the pulse
      amplitude modulated quenching analysis in leaves of Arabidopsis thaliana.
AB  - In their natural environment, plants are exposed to varying light conditions,
      which can lead to a build-up of excitation energy in photosystem (PS) II. Non
      photochemical quenching (NPQ) is the primary defence mechanism employed to
      dissipate this excess energy. Recently, we developed a fluorescence-quenching
      analysis procedure that enables the protective effectiveness of NPQ in intact
      Arabidopsis leaves to be determined. However, pulse-amplitude modulation
      measurements do not currently allow distinguishing between PSII and PSI
      fluorescence levels. Failure to account for PSI contribution is suggested to lead
      to inaccurate measurements of NPQ and, particularly, maximum PSII yield (F v/F
      m). Recently, Pfundel et al. (Photosynth Res 114:189-206, 2013) proposed a method
      that takes into account PSI contribution in the measurements of F o fluorescence
      level. However, when PSI contribution was assumed to be constant throughout the
      induction of NPQ, we observed lower values of the measured minimum fluorescence
      level ([Formula: see text]) than those calculated according to the formula of
      Oxborough and Baker (Photosynth Res 54:135-142 1997) ([Formula: see text]),
      regardless of the light intensity. Therefore, in this work, we propose a refined
      model to correct for the presence of PSI fluorescence, which takes into account
      the previously observed NPQ in PSI. This method efficiently resolves the
      discrepancies between measured and calculated F o' produced by assuming a
      constant PSI fluorescence contribution, whilst allowing for the correction of the
      maximum PSII yield. 

PMID- 25613088
TI  - The whole picture: Child maltreatment experiences of youths who were physically
      abused.
AB  - The purpose of the current study was to describe the maltreatment experiences of
      a sample of urban youths identified as physically abused using the Maltreatment
      Case Record Abstraction Instrument (MCRAI). The sample (n=303) of 9-12 year old
      youths was recruited from active child protective services (CPS) cases in 2002
      2005, and five years of child protective service records were reviewed. The
      demographic and maltreatment experiences of MCRAI-identified youths with physical
      abuse were compared to maltreated youths who were not physically abused and
      youths who were identified as physically abused by CPS when they entered this
      longitudinal study. T-tests and chi-square tests were used to compare the
      demographics and maltreatment experiences of the sample MCRAI-identified
      physically abused to the sample MCRAI-identified as nonphysically abused
      maltreated by gender. Of the total sample, 156 (51%) were identified by MCRAI as
      physically abused and 96.8% of these youth also experienced other types of
      maltreatment. Whereas youth with the initial CPS identification of physical abuse
      showed little co-occurrence (37.7%) with other forms of maltreatment. The MCRAI
      identified physically abused youths had a significantly higher mean number of CPS
      reports and higher mean number of incidents of maltreatment than MCRAI-identified
      nonphysically maltreated youths. Lifeline plots of case record history from the
      time of first report to CPS to entry into the study found substantial individual
      variability in maltreatment experiences for both boys and girls. Thus, obtaining
      maltreatment information from a single report vastly underestimates the
      prevalence of physical abuse and the co-occurrence of other maltreatment types. 

PMID- 25613089
TI  - A linguistic analysis of grooming strategies of online child sex offenders:
      Implications for our understanding of predatory sexual behavior in an
      increasingly computer-mediated world.
AB  - There is a large body of evidence to suggest that child sex offenders engage in
      grooming to facilitate victimization. It has been speculated that this step-by
      step grooming process is also used by offenders who access their underage victims
      online; however, little research has been done to examine whether there are
      unique aspects of computer-mediated communication that impact the traditional
      face-to-face grooming process. This study considered the similarities and
      differences in the grooming process in online environments by analyzing the
      language used by online offenders when communicating with their victims. The
      transcripts of 44 convicted online offenders were analyzed to assess a proposed
      theory of the online grooming process (O'Connell, 2003). Using a stage-based
      approach, computerized text analysis examined the types of language used in each
      stage of the offender-victim interaction. The transcripts also were content
      analyzed to examine the frequency of specific techniques known to be employed by
      both face-to-face and online offenders, such as flattery. Results reveal that
      while some evidence of the strategies used by offenders throughout the grooming
      process are present in online environments, the order and timing of these stages
      appear to be different. The types (and potential underlying pattern) of
      strategies used in online grooming support the development of a revised model for
      grooming in online environments. 

PMID- 25613090
TI  - Alcohol and ischaemic heart disease risk--finally moving beyond interpretation of
      observational epidemiology.

PMID- 25613091
TI  - Endosymbiotic candidates for parasitoid defense in exotic and native New Zealand
      weevils.
AB  - Some insects are infected with maternally inherited bacterial endosymbionts that
      protect them against pathogens or parasitoids. The weevil Sitona obsoletus
      (=Sitona lepidus) is invasive in New Zealand, and suspected to contain such
      defensive symbionts, because it is particularly resistant to a Moroccan strain of
      the parasitoid Microctonus aethiopoides (which successfully attacks many other
      weevil species), and shows geographic variation in susceptibility to an Irish
      strain of the same parasitoid. Using 454 pyrosequencing, we investigated the
      bacterial community associated with S. obsoletus, two other exotic weevils
      (Sitona discoideus and Listronotus bonariensis) and two endemic New Zealand
      weevils (Irenimus aequalis and Steriphus variabilis). We found that S. obsoletus
      was infected by one strain of Wolbachia and two strains of Rickettsia, none of
      which were found in any other weevil species examined. Using diagnostic PCR, we
      found that S. obsoletus in the Northland region, where parasitism is highly
      variable, were primarily infected with Wolbachia and Rickettsia strain 2,
      indicating that these two symbionts should be investigated for potential
      defensive properties. In comparison, S. discoideus lacked any apparent maternally
      inherited bacterial endosymbionts. In the other weevil species, we found a
      different strain of Wolbachia and two different strains of Spiroplasma. Two
      weevil species (St. variabilis and L. bonariensis) were infected with distinct
      strains of Nardonella, the ancestral endosymbiont of weevils, whereas three
      weevil species (S. obsoletus, S. discoideus, and I. aequalis) lacked evidence for
      Nardonella infection. However, I. aequalis was consistently infected with a novel
      Enterobacteriaceae strain, suggesting that a symbiont replacement may have taken
      place, similar to that described for other weevil clades. 

PMID- 25613092
TI  - Anti-OX40L monoclonal antibody prolongs secondary heart allograft survival based
      on CD40/CD40L and LFA-1/ICAM-1 blockade.
AB  - BACKGROUND: Memory T cells (Tms) form a barrier against long-term allograft
      survival; however, CD4(+)Foxp3(+) regulatory T cells (Tregs) can suppress
      allograft rejection. The OX40/OX40L pathway is critical to the generation of Tms
      and turns off Treg suppressor function. METHODS: B6 mice that rejected BALB/c
      skin grafts after 4 weeks were used as the secondary heart transplant recipients.
      The skin recipient mice, termed S0, S2 and S3, were treated with the isotype
      antibodies, anti-CD40L/LFA-1 or anti-OX40L combined with anti-CD40L/LFA-1 mAbs,
      respectively. The secondary heart recipients, termed H0 and H2, received anti
      CD40L/LFA-1 mAbs or not, respectively (Fig. 1). RESULTS: Four weeks after primary
      skin transplantation, the Tms in the S3 group that received anti-OX40L with anti
      CD40L/LFA-1 mAbs were reduced compared to those in the S2 group (CD4(+) Tm: 32.61
      +/- 2.20% in S2 vs. 25.36 +/- 1.16% in S3; CD8(+) Tm: 27.76 +/- 1.96% in S2 vs.
      20.95 +/- 1.30% in S3; P < 0.01). Meanwhile, the proportions of Tregs in S3
      increased compared to those in S2 (P < 0.05). The anti-OX40L with anti-CD40L/LFA
      1 mAbs group (S3H2) prolonged the mean survival time (MST) following secondary
      heart transplantation from 9.5 days to 21 days (P < 0.001). Furthermore,
      allogeneic proliferation of recipient splenic T cells and graft-infiltrating
      lymphocytes were significantly inhibited in the S3H2 group. Additionally, a
      higher level of IL-10 was detected in sera and allografts. CONCLUSIONS: Anti
      OX40L mAb could prolong secondary heart allograft survival based on CD40/CD40L
      and LFA-1/ICAM-1 blockade. The mechanism of protecting allografts using anti
      OX40L mAb involved impairing the generation of Tm and up-regulating IL-10
      producing Tregs, inhibiting the function of T cells.

PMID- 25613094
TI  - [A late debut of childhood disintegrative disorder].
AB  - Actualized by the ongoing discussion of whether childhood disintegrative disorder
      is a diagnostic entity, we describe a case which in every aspect fulfils the ICD
      10 criteria. A girl with a previous normal development who, from the age of 60
      months, experienced a regression during 2-3 months with significant co-morbid
      psychiatric symptoms, leaving her in a state of mental retardation and autism. A
      thorough somatic assessment was normal. The importance of recognition of the
      condition and an integrated child psychiatric and paediatric assessment is
      emphasized. 

PMID- 25613093
TI  - Early phase glucagon and insulin secretory abnormalities, but not incretin
      secretion, are similarly responsible for hyperglycemia after ingestion of
      nutrients.
AB  - AIMS: Hypersecretion of glucagon and reduced insulin secretion both contribute to
      hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of
      impaired glucagon and insulin secretions in glucose excursions at the various
      stages of T2DM development remain to be determined. METHODS: The responses of
      glucagon and insulin as well as those of glucose-dependent insulinotropic
      polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were examined before and
      after ingestion of glucose or mixed meal in Japanese subjects with normal or
      impaired glucose tolerance (NGT and IGT) and in non-obese, untreated T2DM of
      short duration. RESULTS: In OGTT, T2DM showed a rise in glucagon at 0-30 min,
      unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a
      rise in glucagon at 0-30 min, with that in T2DM being highest, while T2DM showed
      a significant reduction in insulin. Linear regression analyses revealed that
      glucose area under the curve (AUC)0-120 min was associated with glucagon-AUC0-30
      min and insulin-AUC0-30 min in both OGTT and MTT. Total and biologically intact
      GIP and GLP-1 levels were similar among the three groups. CONCLUSIONS: Disordered
      early phase insulin and glucagon secretions but not incretin secretion are
      involved in hyperglycemia after ingestion of nutrients in T2DM of even a short
      duration.

PMID- 25613095
TI  - [Treatment of spasticity in children with cerebral palsy with botulinum toxin A].
AB  - Over the latest 30 years there has been an increasing use of botulinum toxin A
      injections in the lower limbs in children with cerebral palsy. However, the
      conclusions regarding effect of treatment in both randomized controlled and non
      controlled trials have been inconclusive. One explanation may be that children
      with cerebral palsy do not always exhibit pure spasticity and/or dystonia of the
      affected muscles. Furthermore, the dose, injection volume and injection technique
      may vary from study to study. The evidence for the effect is so small that
      careful consideration on whether to continue this treatment regimen or not is
      needed. 

PMID- 25613096
TI  - [Laparoscopy-guided liver abscess drainage of multiple large formations].
AB  - A 50-year-old woman was admitted with abdominal pain, vomiting, fever and
      diarrhoea. She had increased white blood cell count and increased level of liver
      enzymes. A CT scan revealed 13 abscesses in the liver and tests showed
      Streptococcus angin-osus. Investigation showed no entry point for bacteria. The
      woman underwent laparoscopic investigation, and the absces-ses were completely
      drained preoperatively without installation of catheter in spite of large abscess
      formations. After 26 days of admittance with antibiotic treatment she was
      discharged and check-up revealed no re-formation of the abscesses. 

PMID- 25613097
TI  - [Heterotopic pancreas is a rare cause of bleeding and intestinal
      intussusception].
AB  - A young female had neurofibromatosis, annular pancreas and heterotopic pancreas,
      a combination not previously described. The tumour caused bleeding and
      intussusception of the distal part of the small intestine. An extensive range of
      examinations was initiated; however, the diagnosis was not clarified until
      explorative laparoscopy was performed. Heterotopic pancreas is worth considering
      as an infrequent cause of gastrointestinal bleeding and invagination. 

PMID- 25613098
TI  - [Non-occupational pleural mesothelioma].
AB  - Asbestos fibres is the only known cause of malignant mesothelioma (MM). The risk
      of MM is increased also by low and brief exposure. MM has a latency of 20-50
      years. We report two cases of MM who were exposed to asbestos during do-it
      yourself roof renovation including cutting and drilling in roof sheeting
      containing asbestos. A detailed occupational history revealed no occupational
      exposure. The two cases demonstrate the importance of careful handling of
      products containing asbestos, with emphasis on avoidance of inhaling asbestos
      fibres. 

PMID- 25613099
TI  - Evaluation of Candidate Genes Related  to Neuronal Apoptosis in Late-Onset 
      Alzheimer's Disease.
AB  - The objective of this study was to identify genetic variation in genes encoding
      death receptors and signals that modulate their activity. After conducting a meta
      analysis with five previous genome-wide association studies and aggregated data,
      the most significant signals, (TNF locus: rs2395488, rs2534672, and rs9267445;
      and FASLG locus: rs730278), were replicated in 1,046 cases and 372 controls. The
      rs2395488 and rs2534672 markers showed a modest protective effect (OR = 0.849, p
      = 0.49780;OR= 0.687, p = 0.11335), in contrast to rs730278 marker (OR = 1.146, p
      = 0.17212), which did not follow the previous effect direction; in any case it
      reached the significance level. Final meta-analysis, adding the replication
      sample, confirmed these observations. We concluded that FASLG marker is not
      etiologically linked to Alzheimer's disease. However, single nucleotide
      polymorphisms around TNF locus require further analyses in order to explain the
      association between Alzheimer's disease and human leukocyte antigen.

PMID- 25613101
TI  - Serum NGAL is Associated with Distinct Plasma Amyloid-beta Peptides According to
      the Clinical Diagnosis of Dementia in Down Syndrome.
AB  - BACKGROUND: The majority of people with Down syndrome (DS) develop dementia due
      to Alzheimer's disease (AD). Neuropathological features are characterized by an
      accumulation of amyloid-beta (Abeta) deposits and the presence of an activated
      immune response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a newly
      identified (neuro)inflammatory constituent in AD. OBJECTIVE: This study examines
      NGAL as an inflammatory marker in DS and its associations with plasma Abeta
      peptides according to the follow-up clinical diagnosis of dementia. METHODS:
      Baseline serum NGAL and plasma Abeta40, Abeta42, Abeta(n40), and Abeta(n42) were
      quantified in 204 people with DS. The diagnosis of dementia in DS was established
      by follow-up clinical assessments. The following study groups were characterized:
      DS with AD at baseline (n = 67), DS without AD (n = 53), and non-demented DS
      individuals that converted to AD (n = 84). Serum NGAL was analyzed in 55 elderly
      non-DS, non-demented people. RESULTS: Serum NGAL levels were significantly
      increased in DS subjects compared to non-DS people. Serum NGAL levels were not
      associated with clinical dementia symptoms in DS. However, NGAL was positively
      associated with Abeta42 and Abeta(n42) in demented DS individuals and with
      Abeta40 and Abeta(n40) in the non-demented DS group. NGAL was negatively
      associated with Abeta42/Abeta40 and Abeta(n42)/Abeta(n40) ratios in converted DS
      subjects. These associations persisted for Abeta(n40), Abeta42/Abeta40, and
      Abeta(n42)/Abeta(n40) after adjusting for demographics measures, apolipoprotein E
      epsilon4 allele, platelets, and anti-inflammatory medication. CONCLUSION: Serum
      NGAL levels are increased in DS and associated with distinct species of Abeta
      depending on the progression of dementia as diagnosed by baseline and follow-up
      clinical assessments.

PMID- 25613100
TI  - Diagnostic Values of Cerebrospinal Fluid T-Tau and Abeta42 using Meso Scale
      Discovery Assays for Alzheimer's Disease.
AB  - BACKGROUND: Meso Scale Discovery (MSD) recently established
      electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels
      of total tau (t-tau) and amyloid-beta 1-42 peptide (Abeta42) that can aid in the
      diagnosis of Alzheimer's disease (AD). The goal of this investigation is to
      independently evaluate this platform and establish cut-off values of these
      biomarkers for AD diagnosis. OBJECTIVE: To validate the analytical and clinical
      performance of the MSD t-tau and Abeta42 kits and propose diagnostic cut-off
      values for the field. METHODS: The analytical performance of the CSF t-tau and
      Abeta42 assays was determined, followed by assessment of diagnostic performance
      of CSF t-tau, Abeta42, and t-tau/Abeta42 in three clinically characterized
      cohorts. RESULTS: Both MSD assays demonstrated consistent and stable analytical
      performance, as well as resistance to several important pre-analytic variables.
      Diagnostically, t-tau/Abeta42 performed the best. CONCLUSIONS: Our results
      independently confirm the analytical and clinical performance of the MSD CSF t
      tau and Abeta42 assays. Based on a large, multi-center, clinically-diagnosed
      cohort, we propose for the first time candidate diagnostic cut-offs for MSD
      measured CSF t-tau, Abeta42, and t-tau/Abeta42. However, these values needs to be
      refined as more subjects are included and the assays are tested by other
      laboratories.

PMID- 25613102
TI  - Cortical brain connectivity evaluated by graph theory in dementia: a correlation
      study between functional and structural data.
AB  - A relatively new approach to brain function in neuroscience is the "functional
      connectivity", namely the synchrony in time of activity in anatomically-distinct
      but functionally-collaborating brain regions. On the other hand, diffusion tensor
      imaging (DTI) is a recently developed magnetic resonance imaging (MRI)-based
      technique with the capability to detect brain structural connection with
      fractional anisotropy (FA) identification. FA decrease has been observed in the
      corpus callosum of subjects with Alzheimer's disease (AD) and mild cognitive
      impairment (MCI, an AD prodromal stage). Corpus callosum splenium DTI
      abnormalities are thought to be associated with functional disconnections among
      cortical areas. This study aimed to investigate possible correlations between
      structural damage, measured by MRI-DTI, and functional abnormalities of brain
      integration, measured by characteristic path length detected in resting state EEG
      source activity (40 participants: 9 healthy controls, 10 MCI, 10 mild AD, 11
      moderate AD). For each subject, undirected and weighted brain network was built
      to evaluate graph core measures. eLORETA lagged linear connectivity values were
      used as weight of the edges of the network. Results showed that callosal FA
      reduction is associated to a loss of brain interhemispheric functional
      connectivity characterized by increased delta and decreased alpha path length.
      These findings suggest that "global" (average network shortest path length
      representing an index of how efficient is the information transfer between two
      parts of the network) functional measure can reflect the reduction of fiber
      connecting the two hemispheres as revealed by DTI analysis and also anticipate in
      time this structural loss. 

PMID- 25613103
TI  - Bayesian graphical network analyses reveal complex biological interactions
      specific to Alzheimer's disease.
AB  - With different approaches to finding prognostic or diagnostic biomarkers for
      Alzheimer's disease (AD), many studies pursue only brief lists of biomarkers or
      disease specific pathways, potentially dismissing information from groups of
      correlated biomarkers. Using a novel Bayesian graphical network method, with data
      from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the
      aim of this study was to assess the biological connectivity between AD associated
      blood-based proteins. Briefly, three groups of protein markers (18, 37, and 48
      proteins, respectively) were assessed for the posterior probability of biological
      connection both within and between clinical classifications. Clinical
      classification was defined in four groups: high performance healthy controls
      (hpHC), healthy controls (HC), participants with mild cognitive impairment (MCI),
      and participants with AD. Using the smaller group of proteins, posterior
      probabilities of network similarity between clinical classifications were very
      high, indicating no difference in biological connections between groups.
      Increasing the number of proteins increased the capacity to separate both hpHC
      and HC apart from the AD group (0 for complete separation, 1 for complete
      similarity), with posterior probabilities shifting from 0.89 for the 18 protein
      group, through to 0.54 for the 37 protein group, and finally 0.28 for the 48
      protein group. Using this approach, we identified beta-2 microglobulin (beta2M)
      as a potential master regulator of multiple proteins across all classifications,
      demonstrating that this approach can be used across many data sets to identify
      novel insights into diseases like AD. 

PMID- 25613104
TI  - Characteristic features of reproductive hormone profiles in late adolescent and
      adult females with complete androgen insensitivity syndrome.
AB  - Little is known about gonadotropins and sex steroid levels in postpubertal women
      with complete androgen insensitivity syndrome (CAIS). In order to define
      reproductive hormone profiles in women with CAIS and intact gonads, 42
      postpubertal females with proven CAIS (age range 14-50 years) with testes in situ
      were examined. Reproductive hormone values [testosterone (T), estradiol (E2), sex
      hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating
      hormone (FSH)] were assessed by commercially available immunoassays. In women
      with CAIS, LH levels (median 18.5 IU/l, range 5.5-51.1 IU/l) were elevated above
      the usual adult reference ranges, whereas FSH values (3.5 IU/l, 0.4-16.3 IU/l)
      were not. Basal T (20 nmol/l, 6-52 nmol/l) and E2 values (113 pmol/l; 18-257
      pmol/l) were found in the usual adult male reference ranges; SHBG levels (53
      nmol/l, 15-180 nmol/l) were in the adult female reference range. Calculated free
      androgen indices (Tx103/SHBG: 380, 114-863) and aromatization indices (E2/T:
      0.052, 0.020-0.196) did not differ from the reference ranges for adult men given
      in the literature (Tx103/SHBG: 315-936; E2/T: 0.03-0.07). Reproductive hormone
      profiles in women with CAIS do not follow the usual male/female pattern,
      suggesting a specific postpubertal hormone milieu. Albeit calculation of CAIS
      specific reference ranges requires larger series and standardization of
      laboratory methods, these results may be a prerequisite for the identification of
      pathologic hormone patterns in women with CAIS and gonads in situ. The present
      data will also be useful to monitor hormone replacement therapy in individuals
      with removed gonads.

PMID- 25613105
TI  - Gender-based Outcomes and Acceptability of a Computer-assisted Psychosocial
      Intervention for Substance Use Disorders.
AB  - BACKGROUND: Digital technologies show promise for increasing treatment
      accessibility and improving quality of care, but little is known about gender
      differences. This secondary analysis uses data from a multi-site effectiveness
      trial of a computer-assisted behavioral intervention, conducted within NIDA's
      National Drug Abuse Clinical Trials Network, to explore gender differences in
      intervention acceptability and treatment outcomes. METHODS: Men (n=314) and women
      (n=192) were randomly assigned to 12-weeks of treatment-as-usual (TAU) or
      modified TAU+Therapeutic Education System (TES), whereby TES substituted for
      2hours of TAU per week. TES is composed of 62 Web-delivered, multimedia modules,
      covering skills for achieving and maintaining abstinence plus prize-based
      incentives contingent on abstinence and treatment adherence. Outcomes were: (1)
      abstinence from drugs and heavy drinking in the last 4weeks of treatment, (2)
      retention, (3) social functioning, and (4) drug and alcohol craving.
      Acceptability was the mean score across five indicators (i.e., interesting,
      useful, novel, easy to understand, and satisfaction). RESULTS: Gender did not
      moderate the effect of treatment on any outcome. Women reported higher
      acceptability scores at week 4 (p=.02), but no gender differences were detected
      at weeks 8 or 12. Acceptability was positively associated with abstinence, but
      only among women (p=.01). CONCLUSIONS: Findings suggest that men and women derive
      similar benefits from participating in a computer-assisted intervention, a
      promising outcome as technology-based treatments expand. Acceptability was
      associated with abstinence outcomes among women. Future research should explore
      characteristics of women who report less satisfaction with this modality of
      treatment and ways to improve overall acceptability.

PMID- 25613106
TI  - Ligand recognition specificity of leukocyte integrin alphaMbeta2 (Mac-1,
      CD11b/CD18) and its functional consequences.
AB  - The broad recognition specificity exhibited by integrin alpha(M)beta2 (Mac-1,
      CD11b/CD18) has allowed this adhesion receptor to play innumerable roles in
      leukocyte biology, yet we know little about how and why alpha(M)beta2 binds its
      multiple ligands. Within alpha(M)beta2, the alpha(M)I-domain is responsible for
      integrin's multiligand binding properties. To identify its recognition motif, we
      screened peptide libraries spanning sequences of many known protein ligands for
      alpha(M)I-domain binding and also selected the alpha(M)I-domain recognition
      sequences by phage display. Analyses of >1400 binding and nonbinding peptides
      derived from peptide libraries showed that a key feature of the alpha(M)I-domain
      recognition motif is a small core consisting of basic amino acids flanked by
      hydrophobic residues. Furthermore, the peptides selected by phage display
      conformed to a similar pattern. Identification of the recognition motif allowed
      the construction of an algorithm that reliably predicts the alpha(M)I-domain
      binding sites in the alpha(M)beta2 ligands. The recognition specificity of the
      alpha(M)I-domain resembles that of some chaperones, which allows it to bind
      segments exposed in unfolded proteins. The disclosure of the alpha(M)beta2
      binding preferences allowed the prediction that cationic host defense peptides,
      which are strikingly enriched in the alpha(M)I-domain recognition motifs,
      represent a new class of alpha(M)beta2 ligands. This prediction has been tested
      by examining the interaction of alpha(M)beta2 with the human cathelicidin peptide
      LL-37. LL-37 induced a potent alpha(M)beta2-dependent cell migratory response and
      caused activation of alpha(M)beta2 on neutrophils. The newly revealed recognition
      specificity of alpha(M)beta2 toward unfolded protein segments and cationic
      proteins and peptides suggests that alpha(M)beta2 may serve as a previously
      proposed "alarmin" receptor with important roles in innate host defense.

PMID- 25613107
TI  - Characterisation of the frequent exacerbator phenotype in COPD patients in a
      large UK primary care population.
AB  - BACKGROUND: The 'frequent exacerbator' is recognised as an important phenotype in
      COPD. Current understanding about this phenotype comes from prospective
      longitudinal clinical trials in secondary/tertiary care with little information
      reported in primary care populations. AIMS: To characterize the frequent
      exacerbator phenotype and identify associated risk factors in a large UK primary
      care COPD population. METHODS: Using a large database of primary care patients
      from 80 UK general practices, patients were categorised using GOLD 2014 criteria
      into high and low risk groups based on exacerbation history. A multivariate
      logistic regression model was used to investigate covariates associated with the
      frequent-exacerbator phenotype and risk of experiencing a severe exacerbation
      (leading to hospitalisation). RESULTS: Of the total study population (n = 9219),
      2612 (28%) fulfilled the criteria for high risk frequent-exacerbators.
      Independent risk factors (adjusted odds ratio [95% CI]) for >=2 exacerbations
      were: most severely impaired modified Medical Research Council (mMRC) dyspnoea
      score (mMRC grade 4: 4.37 [2.64-7.23]), lower FEV1 percent predicted (FEV1 <30%:
      2.42 [1.61-3.65]), co-morbid cardiovascular disease (1.42 [1.19-1.68]),
      depression (1.56 [1.22-1.99]) or osteoporosis (1.54 [1.19-2.01]), and female
      gender (1.20 [1.01-1.43]). Older patients (>=75 years), those with most severe
      lung impairment (FEV1 <30%), those with highest mMRC score and those with co
      morbid osteoporosis were identified as most at risk of experiencing exacerbations
      requiring hospitalisation. CONCLUSIONS: Although COPD exacerbations occur across
      all grades of disease severity, female patients with high dyspnoea scores, more
      severely impaired lung function and co-morbidities are at greatest risk. Elderly
      patients, with severely impaired lung function, high mMRC scores and osteoporosis
      are associated with experience of severe exacerbations requiring hospitalisation.

PMID- 25613108
TI  - Role of BNP and echo measurement for pulmonary hypertension recognition in
      patients with interstitial lung disease: An algorithm application model.
AB  - BACKGROUND: This study evaluated the role of echocardiography and BNP in patients
      with interstitial lung disease (ILD), to identify those with PH and RV
      dysfunction. The aims of this study were: 1-to evaluate the accuracy of an
      algorithm including BNP, DLCO and echocardiographic measurements to identify PH
      and RV dysfunction; 2- to evaluate BNP and Echo values concordance in relation to
      right catheterization measurement. METHODS: We analyzed 113 patients with
      diagnosis of ILD. Echo examination included: Pulmonary systolic, diastolic and
      mean Arterial Pressure (PAPs, PAPd, PAP mean), End-Diastolic and End-Systolic
      right ventricle diameters, Inferior Caval Vein diameter, and Tricuspid Annular
      Plane Systolic Excursion (TAPSE). Patients revealing increased PAPs at
      echocardiography underwent to catheterization. RESULTS: Patients with PAPs > 40
      mm Hg (37 patients), PAPmean >= 25 mm Hg (23 patients) and PAPd >= 20 mm Hg
      showed BNP increased (157 +/- 96 vs 16 +/- 14 pg/ml p = 0.004; 201 +/- 120 vs 28
      +/- 17 pg/mL; 124 +/- 88 vs 23 +/- 18 pg/ml p < 0.001) as patients with TAPSE
      <=16 mm (25 patients) (145 +/- 104 vs 26 +/- 21 pg/ml p < 0.001). In catheterized
      patients (37 patients) BNP was increased in patients with invasive PAPs > 40 mm
      Hg (165 +/- 112 vs 29 +/- 14 pg/ml p < 0.02), as well as in patients with Wedge
      pressure > 14 mm Hg (199 + 153 vs 54 + 39 pg/mL; p = 0.01). ROC Curve analysis
      showed that elevated values of BNP, PAPs, PAP mean are able to assess PH. On the
      other hand, lower values of DLCO (<40%) and TAPSE (<=16 mm) detect PH. Logistic
      regression analysis of the previous parameters, confirmed their diagnostic role
      in PH detection. CONCLUSIONS: In patients with ILD, an algorithm including BNP,
      DLCO and echocardiography could be useful for non invasive screening of PH.
      CLINICAL TRIAL REGISTRATION NAME AND NUMBER: ARTEMIS-HP trial; ID number:
      NCT00879229.

PMID- 25613109
TI  - Age-related and historical changes in the clinical characteristics of sarcoidosis
      in Japan.
AB  - BACKGROUND: National surveys conducted in Japan between 1960 and 2004 suggest a
      gradually increasing incidence of sarcoidosis in women >50 years old with
      increased involvement of the eye, skin, and heart. However, whether this
      involvement is due to the increased age at diagnosis is still unclear. We aimed
      here to identify the age-related differences in organ involvement in sarcoidosis
      in Japan, as well as the historical changes in clinical characteristics and the
      age-specific distribution of cases at diagnosis. METHODS: We reviewed 588
      consecutive Japanese patients newly diagnosed with sarcoidosis between 1974 and
      2012 at Jichi Medical University Hospital. We compared organ involvement between
      subgroups differentiated by sex and age (<45 years; n = 275; >=45 years; n = 313)
      at diagnosis and identified historical changes in the age-specific distribution
      in 10-year intervals. RESULTS: Younger patients had more common involvement of
      extrathoracic lymph nodes, parotid/salivary gland, and liver, while older
      patients had more common involvement of non-lymphatic extrathoracic organs such
      as the eye, heart, muscle, and kidney. The age at diagnosis has consistently
      increased over the past four decades. The monophasic distribution in men has
      tended to become biphasic, and the biphasic distribution in women monophasic.
      Increasing trends were apparent for hypercalcemia and involvement of the
      gastrointestinal tract, skin, nervous system, muscle, and kidney. CONCLUSIONS:
      Elderly patients at diagnosis had various extrathoracic involvement including
      eye, skin, and cardiac lesions. Moreover, the age at diagnosis of sarcoidosis has
      continued to increase in both sexes, influencing the recent trends in clinical
      characteristics.

PMID- 25613110
TI  - Testing mapping algorithms of the cancer-specific EORTC QLQ-C30 onto EQ-5D in
      malignant mesothelioma.
AB  - BACKGROUND: In order to estimate utilities for cancer studies where the EQ-5D was
      not used, the EORTC QLQ-C30 can be used to estimate EQ-5D using existing mapping
      algorithms. Several mapping algorithms exist for this transformation, however,
      algorithms tend to lose accuracy in patients in poor health states. The aim of
      this study was to test all existing mapping algorithms of QLQ-C30 onto EQ-5D, in
      a dataset of patients with malignant pleural mesothelioma, an invariably fatal
      malignancy where no previous mapping estimation has been published. METHODS:
      Health related quality of life (HRQoL) data where both the EQ-5D and QLQ-C30 were
      used simultaneously was obtained from the UK-based prospective observational
      SWAMP (South West Area Mesothelioma and Pemetrexed) trial. In the original trial
      73 patients with pleural mesothelioma were offered palliative chemotherapy and
      their HRQoL was assessed across five time points. This data was used to test the
      nine available mapping algorithms found in the literature, comparing predicted
      against observed EQ-5D values. The ability of algorithms to predict the mean,
      minimise error and detect clinically significant differences was assessed.
      RESULTS: The dataset had a total of 250 observations across 5 timepoints. The
      linear regression mapping algorithms tested generally performed poorly, over
      estimating the predicted compared to observed EQ-5D values, especially when
      observed EQ-5D was below 0.5. The best performing algorithm used a response
      mapping method and predicted the mean EQ-5D with accuracy with an average root
      mean squared error of 0.17 (Standard Deviation; 0.22). This algorithm reliably
      discriminated between clinically distinct subgroups seen in the primary dataset.
      CONCLUSIONS: This study tested mapping algorithms in a population with poor
      health states, where they have been previously shown to perform poorly. Further
      research into EQ-5D estimation should be directed at response mapping methods
      given its superior performance in this study.

PMID- 25613111
TI  - Tuning the excited state of water-soluble Ir(III)-based DNA intercalators that
      are isostructural with [Ru(II)(NN)2(dppz)] light-switch complexes.
AB  - The synthesis of two new Ir(III)  complexes which are effectively isostructural
      with well-established [Ru(NN)2(dppz)](2+) systems is reported
      (dppz=dipyridophenazine; NN=2,2'-bipyridyl, or 1,10-phenanthroline). One of these
      Ir(III) complexes is tricationic and has a conventional N6 coordination sphere.
      The second dicationic complex has a N5C coordination sphere, incorporating a
      cyclometalated analogue of the dppz ligand. Both complexes show good water
      solubility. Experimental and computational studies show that the photoexcited
      states of the two complexes are very different from each other and also differ
      from their Ru(II) analogues. Both of the complexes bind to duplex DNA with
      affinities that are two orders of magnitude higher than previously reported
      Ir(dppz)-based systems and are comparable with Ru(II)(dppz) analogues.

PMID- 25613112
TI  - The relationship between obstructive sleep apnea syndrome and apolipoprotein E
      genetic variants.
AB  - BACKGROUND: Clinical and epidemiological studies indicate that obstructive sleep
      apnea syndrome (OSAS) has a strong genetic basis. OBJECTIVES: To investigate the
      apolipoprotein E (APOE) alleles as a genetic risk factor in OSAS. METHODS: A
      total of 73 patients (37 male) were included. All underwent full-night
      polysomnography and were evaluated for APOE alleles. RESULTS: The mean age was 51
      +/- 12 years. Forty-two of the patients had OSAS. The APOE3 allele was found in
      97.3% (71/73) of the study population. The most common APOE genotype was E3/E3
      (55/73, 75.3%). Compared to the individuals with no APOE2 alleles (E3/E3, E3/E4),
      the individuals with at least one APOE2 allele (E2/E3, E2/E4) had a 9.37-fold
      greater OSAS risk (OR = 9.37, 95% CI 1.13-77.7, p = 0.019). The individuals with
      APOE2 alleles (E2/E3, E2/E4) compared to the individuals with only an E3/E3
      allele genotype had a 10-fold greater OSAS risk (OR = 10.3, 95% CI 1.24-86.61, p
      = 0.0308). Compared to the individuals with no APOE4 alleles (E2/E3, E3/E3), the
      individuals with APOE4 alleles (E2/E4, E3/E4) had a high but insignificant risk
      for OSAS (OR = 2.9, 95% CI 0.55-15.05, p = 0.286). The individuals with APOE4
      alleles (E2/E4, E3/E4) compared to APOE3 alleles (E3/E3) had an increased but
      insignificant risk for OSAS (OR = 3.62, 95% CI 0.96-19.05, p = 0.127).
      CONCLUSION: Specific APOE genotypes are associated with OSAS in a high-risk
      population.

PMID- 25613115
TI  - Association between C-reactive protein, incident liver cancer, and chronic liver
      disease mortality in the Linxian Nutrition Intervention Trials: a nested case
      control study.
AB  - BACKGROUND: C-reactive protein (CRP) is a marker of systemic inflammation that
      has been associated with the incidence and prognosis for a number of different
      cancers. Recent data suggest that CRP may be a prognostic factor for liver cancer
      and cirrhosis. However, few long-term studies are available. METHODS: We
      prospectively examined associations between serum CRP and subsequent risk of
      liver cancer incidence or chronic liver disease mortality in a nested case
      control study performed in the Linxian Nutrition Intervention Trials cohort.
      Baseline serum CRP was measured for 220 incident liver cancer cases, 276
      participants who died of chronic liver disease, and 1,018 age-, sex-, and trial
      matched controls. Unconditional logistical regression models were used to
      estimate ORs and 95% confidence intervals (CI). RESULTS: Compared with the lowest
      quartile, subjects in the fourth quartile of serum CRP had a higher risk of liver
      cancer incidence (OR, 1.63; 95% CI, 1.06-2.51), with a significant Ptrend across
      quartiles (P = 0.01). The association with liver cancer was only significant
      among men (Q4 vs. Q1; OR, 2.00; 1.10-3.62), but not among women (Q4 vs. Q1; OR,
      1.15; 0.60-2.22). For chronic liver disease deaths, the corresponding risk
      estimate in men and women was 2.95 (1.90-4.57), with a monotonic trend (P <
      0.001). CONCLUSIONS: Higher serum CRP concentrations at baseline were associated
      with subsequent incidence of liver cancer and death from chronic liver disease.
      IMPACT: Our findings suggest that levels of systemic inflammation may serve as a
      long-term marker of liver cancer and liver disease.

PMID- 25613116
TI  - Association of Nonsteroidal Anti-Inflammatory Drugs with Colorectal Cancer by
      Subgroups in the VITamins and Lifestyle (VITAL) Study.
AB  - BACKGROUND: There is substantial evidence that use of NSAIDs reduces the risk of
      colorectal cancer, but no subgroup has been identified for which the
      chemoprevention effect outweighs the risk of side effects. METHODS: We tested the
      interaction between NSAID use and multiple risk factors on colorectal cancer risk
      in the VITAL cohort. A total of 73,458 individuals ages 50 to 76 years completed
      a questionnaire between 2000 and 2002, and 674 incidental colorectal cancer cases
      were identified through 2010. RESULTS: In stratified analysis, high use of any
      type of NSAIDs (4+ days/week for 4+ years) was statistically significantly
      associated with a lower risk of colorectal cancer across all subgroups stratified
      by sex, body mass index, physical activity, smoking, alcohol intake, screening,
      and dietary factors. There was a suggestion of stronger associations among men,
      obese individuals, and heavier drinkers; however, none of these tests for
      interaction reached statistical significance. The associations were almost
      identical for subjects with higher overall colorectal cancer risk scores [HR,
      0.62; 95% confidence interval (CI), 0.49-0.79] and those with lower risk scores
      (HR, 0.61; 95% CI, 0.42-0.88). Differential effects by cancer subsites and stages
      were tested. NSAID use was associated with a greater risk reduction of proximal
      colon cancer versus distal (P for difference = 0.06) and distant stage versus
      local (P for difference = 0.04). CONCLUSION: The association between high use of
      NSAIDs and colorectal cancer risk does not differ significantly among subgroups.
      IMPACT: Our results suggest that NSAIDs have a generally beneficial role in
      colorectal cancer prevention, largely unmodified by other exposures.

PMID- 25613117
TI  - Projecting Benefits and Harms of Novel Cancer Screening Biomarkers: A Study of
      PCA3 and Prostate Cancer.
AB  - BACKGROUND: New biomarkers for early detection of cancer must pass through
      several phases of development. Early phases provide information on diagnostic
      properties but not on population benefits and harms. Prostate cancer antigen 3
      (PCA3) is a promising prostate cancer biomarker still in early development. We
      use simulation modeling to project the impact of adding PCA3 to prostate-specific
      antigen (PSA) screening on prostate cancer detection and mortality in the United
      States. METHODS: We used data from a recent study of PCA3 in men referred for
      prostate biopsy to extend an existing simulation model of PSA growth, disease
      progression, and survival. We specified several PSA-PCA3 strategies designed to
      improve specificity and reduce overdiagnosis. Using these strategies to screen a
      cohort of men biennially between ages 50 and 74, we projected true- and false
      positive tests, overdiagnoses, and lives saved relative to a PSA-based strategy
      with a cutoff of 4.0 ng/mL for biopsy referral. RESULTS: We identified several
      PSA-PCA3 strategies that substantially reduced false-positive tests and
      overdiagnoses while preserving the majority of lives saved. PCA3>35 for biopsy
      referral in men with PSA between 4.0 and 10.0 ng/mL retained 85% of lives saved
      while approximately halving false positives and reducing overdiagnoses by 25%.
      CONCLUSIONS: Adding PCA3 to PSA screening can significantly reduce adverse
      screening outcomes. Strategies can be identified that preserve most of the lives
      saved relative to PSA-based screening. IMPACT: Simulation modeling provides
      advance projections of population outcomes of new screening biomarkers and may
      help guide early detection research.

PMID- 25613118
TI  - Low-Dose CT Lung Cancer Screening Practices and Attitudes among Primary Care
      Providers at an Academic Medical Center.
AB  - BACKGROUND: Low-dose computed tomography (LDCT) screening reduces lung cancer
      specific and overall mortality. We sought to assess lung cancer screening
      practices and attitudes among primary care providers (PCPs) in the era of new
      LDCT screening guidelines. METHODS: In 2013, we surveyed PCPs at an academic
      medical center (60% response) and assessed: lung cancer screening use, perceived
      screening effectiveness, knowledge of screening guidelines, perceived barriers to
      LDCT use, and interest in LDCT screening education. RESULTS: Few PCPs (n = 212)
      reported ordering lung cancer screening: chest X-ray (21%), LDCT (12%), and
      sputum cytology (3%). Only 47% of providers knew three or more of six guideline
      components for LDCT screening; 24% did not know any guideline components. In
      multiple logistic regression analysis, providers who knew three or more guideline
      components were more likely to order LDCT (OR, 7.1; 95% confidence intervals, 2.0
      25.6). Many providers (30%) were unsure of the effectiveness of LDCT.
      Mammography, colonoscopy, and Pap smear were rated more frequently as effective
      in reducing cancer mortality compared with LDCT (all P values < 0.0001). Common
      perceived barriers included patient cost (86.9% major or minor barrier), harm
      from false positives (82.7%), patients' lack of awareness (81.3%), risk of
      incidental findings (81.3%), and insurance coverage (80.1%). CONCLUSIONS: LDCT
      lung cancer screening is currently an uncommon practice at an academic medical
      center. PCPs report ordering chest X-ray, a nonrecommended screening test, more
      often than LDCT. PCPs had a limited understanding of lung cancer screening
      guidelines and LDCT effectiveness. Provider educational interventions are needed
      to facilitate shared decision-making with patients. IMPACT: This study describes
      some of the first data available about PCPs' use of lung cancer screening tests
      since the publication of multiple professional guidelines endorsing LDCT.
      Knowledge gaps were identified that may hinder the uptake of evidence-based lung
      cancer screening guidelines.

PMID- 25613122
TI  - Ultrasound in the meat industry: general applications and decontamination
      efficiency.
AB  - This review summarizes the findings of research focused on ultrasound as a
      "green", nonchemical technology in the meat industry to improve meat quality and
      safety. An overview of the importance of the decontamination in meat processing
      and microbial inactivation using ultrasound combined with some other applications
      is provided along with results of high power ultrasound studies which have been
      applied and adapted in the meat industry. The research results revealed that
      ultrasound by itself or in combination with other processing and/or preservation
      methods has a potential for improving the general quality, marination and
      tenderness of meat, preventing microbial growth and recontamination in meat and
      meat products as well as for the determination of defects in carcasses and
      cleaning process equipment. This review will provide an interpretation of
      ultrasound applications, an up-to-date summary of published articles, and an
      overview of the microbial inactivation in meat and poultry and their products by
      ultrasound. Since there is a need for not only a pathogen-free product but also a
      quality product; this review also can be accepted as a report on the results of
      research in the field of meat quality improvements with ultrasound applications. 

PMID- 25613119
TI  - Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation
      Location in BRCA1/2 Carriers.
AB  - BACKGROUND: Mutations in BRCA1/2 confer a high risk of breast cancer, but
      literature values of this risk vary. A genotype-phenotype correlation has been
      found in both genes, and the effect of reproductive factors differs according to
      mutation location. Therefore, we hypothesize that such a variation may exist for
      other factors related to estrogen exposure. METHODS: We used a weighted Cox
      regression model to assess variation in breast cancer risk with these factors
      using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in
      the GENEPSO study. RESULTS: We found that late age at menarche reduced breast
      cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual
      cycle increased risk (by 65% and 73%, respectively). Among premenopausal women,
      overweight was associated with a 45% decrease in risk whereas underweight was
      associated with an increased risk (HR, 2.40). A natural menopause, mainly after
      age 50, was associated with a high breast cancer risk (HR, 2.46), and a
      significant interaction between menopause status and the location of mutations
      was found leading up to 10% variation in absolute risk according to the age at
      menopause. CONCLUSIONS: As observed in the general population, a late menarche, a
      long or a short menstrual cycle, over- or underweight, and being postmenopausal
      were associated with breast cancer risk in BRCA1/2 carriers. The association with
      the menopause was observed only when the mutation was located in the "high-risk"
      zones. IMPACT: Taking into account modifier factors, location of mutation might
      be important for the clinical management of BRCA1/2 mutation carriers.

PMID- 25613125
TI  - The Pediatric Cataract Register (PECARE): analysis of age at detection of
      congenital cataract.
AB  - PURPOSE: To analyse and discuss screening for the detection of congenital
      cataract in two Nordic countries, Denmark and Sweden. METHODS: Until 2011, in
      Denmark, no guideline concerning screening for congenital cataract existed. Since
      2011, Danish guidelines regarding eye examination include examination with a
      pencil light at age 5 weeks, whereas newborn red reflex examination using a
      handheld ophthalmoscope is routine protocol in Swedish maternity wards. Data
      regarding age of referral were derived from the Pediatric Cataract Register
      (PECARE). All children operated on before 1 year of age between January 2008 and
      December 2012 were included. Statistical comparison of the different screening
      strategies was made. RESULTS: The number of children undergoing surgery for
      congenital cataract before 1 year of age was 31 (17 bilateral cases) in Denmark
      and 92 (38 bilateral cases) in Sweden. The proportion was 14 per 100.000 children
      in Denmark and 16 in Sweden (p < 0.05). There was a statistically significant
      difference between Denmark and Sweden in the percentage of children referred
      within 42 days of birth (p < 0.0001) and within 100 days (p < 0.001). CONCLUSION:
      Due to the screening procedure with red reflex examination, congenital cataract
      in Swedish children is detected significantly earlier than in Danish children.

PMID- 25613123
TI  - Correlation of hormone receptor status between circulating tumor cells, primary
      tumor, and metastasis in breast cancer patients.
AB  - PURPOSE: Estrogen receptor (ER) and progesterone receptor (PR) status is
      prognostic and predictive in breast cancer. Because metastatic breast tumor
      biopsies are not routinely feasible, circulating tumor cells (CTCs) offer an
      alternative source of determining ER/PR tumor status. METHODS/PATIENTS:
      Peripheral blood was collected prospectively from 36 patients with metastatic
      breast cancer. CTCs were isolated using the microfluidic OncoCEETM platform.
      Detection was accomplished with an expanded anti-cytokeratin (CK) cocktail
      mixture and anti-CD45. ER/PR protein expression was assessed by
      immunocytochemistry (ICC) on the CK+ cells and compared to the primary and/or
      metastatic tumor by immunohistochemistry (IHC). RESULTS: Among the 24 CK + CTC
      cases, a concordance of 68 % (15/22) in ER/PR status between primary breast tumor
      and CTCs and 83 % (10/12) between metastatic tumor and CTCs was observed. An
      overall concordance of 79 % (19/24) was achieved when assessing CTC and
      metastatic tumor (primary tumor substituted if metastatic breast biopsy not
      available). A test sensitivity of 72 % and specificity of 100 % was identified
      when comparing CTCs to tumor tissue. Of the 7 discordant cases between CTCs and
      primary tumor tissue, 2 were concordant with the metastatic biopsy. CONCLUSIONS:
      CTC ER/PR status using the OncoCEETM platform is feasible, with high concordance
      in ER/PR status between tumor tissue (IHC) and CTCs (ICC). The prognostic and
      predictive significance of CTC ER/PR protein expression needs further evaluation
      in larger trials.

PMID- 25613126
TI  - Immunomagnetic detection of micrometastatic cells in bone marrow of uveal
      melanoma patients: a paradox.
AB  - PURPOSE: Our objective was to study survival rates with the bone marrow (BM)
      results in a cohort of uveal melanoma patients with long follow-up. METHODS:
      Mononuclear cell fractions isolated from BM were examined for tumour cells using
      our immunomagnetic separation (IMS) method. The patients were classified as BM
      positive or BM negative. Clinical follow-up, histopathological findings, vital
      status and cause of death were registered. RESULTS: The study included 328
      consecutive patients with uveal melanoma from 1997 to 2006. Tumour cells were
      found in BM samples in 29% (95% CI, 25-34) at enrolment (96 cases). After a
      minimum follow-up time of 6 years, 156 (48%) (95% CI, 42-53) melanoma patients
      had died. The causes were as follows: melanoma metastases 92 (59%), another
      cancer 20 (13%) and non-cancer 44 (28%). Nine patients were still living with
      melanoma metastases. Until the latest work-up, 101(31%) (95% CI, 26-36) patients
      had developed melanoma metastases. Cyto- or histopathological verification of the
      metastatic lesions was obtained in 85 cases (84%). In the group with melanoma
      metastases, 28 tested BM positive at study entry (28%) (95% CI, 19-38). In total,
      39 of 101 with metastases tested positive at least once after a maximum of three
      tests (39%) (95% CI, 29-49). The overall median survival from the first BM test
      was shorter for the BM negative patients (9.5 years) compared with the BM
      positive (14.4 years), p = 0.02, log rank test. CONCLUSION: Ocular melanoma cells
      detected in BM seem to have a positive prognostic impact on survival in contrast
      to our original hypothesis.

PMID- 25613127
TI  - Diabetic macular ischaemia is associated with narrower retinal arterioles in
      patients with type 2 diabetes.
AB  - PURPOSE: Diabetic macular ischaemia (DMI) is an important cause of visual loss in
      patients with diabetes, but its relationship to the larger retinal vessels is
      unknown. We examined whether retinal vessel calibre is related to DMI. METHODS:
      Clinic-based case-control study of patients with type 2 diabetes. The presence
      and severity of DMI was assessed using Early Treatment Diabetic Retinopathy Study
      (ETDRS) protocols from fundus fluorescein angiographic (FFA) images. Custom
      software was used to quantify the greatest linear dimension and area of the
      foveal avascular zone (FAZ). Retinal vessel calibre was measured using a semi
      automated software on fundus fluorescein images. RESULTS: Of 53 patients
      examined, 18 (34%), 18 (34%) and 17 (32%) had no/mild, moderate and severe DMI,
      respectively. Persons with moderate or severe DMI had narrower mean retinal
      arteriolar calibre than persons with no/mild DMI (140.6 MUm 95% confidence
      interval (CI) 134.7, 146.4 versus 150.7 MUm, 95% CI 142.5, 158, p = 0.04). The
      association remained after multivariate adjustment for age, gender, previous
      panretinal photocoagulation, neovascularization at the disc and elsewhere and
      diabetic retinopathy severity. Increased FAZ size was also associated with
      narrower arteriolar calibre. Retinal venular calibre and arteriole to venule
      ratio (AVR) were not associated with DMI. CONCLUSIONS: Retinal arteriolar
      narrowing was associated with moderate-to-severe macular ischaemia in eyes with
      diabetic retinopathy. This suggests that larger vessels other than capillaries
      may also be associated with DMI.

PMID- 25613128
TI  - Increased intraocular pressure after vitreoretinal surgery as a cause of
      ipsilateral amaurosis fugax upon rising to a standing position.

PMID- 25613129
TI  - The independent and interacting effects of hedonic hunger and executive function
      on binge eating.
AB  - Poor executive function (EF; pre-frontal cognitive control processes governing
      goal-directed behavior) and elevated hedonic hunger (i.e., preoccupation with
      palatable foods in the absence of physiological hunger) are theoretical risk and
      maintenance factors for binge eating (BE) distinct from general obesity. Recent
      theoretical models posit that dysregulated behavior such as BE may result from a
      combination of elevated appetitive drive (e.g., hedonic hunger) and decreased EF
      (e.g., inhibitory control and delayed discounting). The present study sought to
      test this model in distinguishing BE from general obesity by examining the
      independent and interactive associations of EF and hedonic hunger with BE group
      status (i.e., odds of categorization in BE group versus non-BE group). Treatment
      seeking overweight and obese women with BE (n = 31) and without BE (OW group; n =
      43) were assessed on measures of hedonic hunger and EF (inhibitory control and
      delay discounting). Elevated hedonic hunger increased the likelihood of
      categorization in the BE group, regardless of EF. When hedonic hunger was low,
      poor EF increased the likelihood of categorization in the BE group. Results
      indicate that the interplay of increased appetitive drives and decreased
      cognitive function may distinguish BE from overweight/obesity. Future
      longitudinal investigations of the combinatory effect of hedonic hunger and EF in
      increasing risk for developing BE are warranted, and may inform future treatment
      development to target these factors. 

PMID- 25613130
TI  - The putative Na+/Cl--dependent neurotransmitter/osmolyte transporter inebriated
      in the Drosophila hindgut is essential for the maintenance of systemic water
      homeostasis.
AB  - Most organisms are able to maintain systemic water homeostasis over a wide range
      of external or dietary osmolarities. The excretory system, composed of the
      kidneys in mammals and the Malpighian tubules and hindgut in insects, can
      increase water conservation and absorption to maintain systemic water
      homeostasis, which enables organisms to tolerate external hypertonicity or
      desiccation. However, the mechanisms underlying the maintenance of systemic water
      homeostasis by the excretory system have not been fully characterized. In the
      present study, we found that the putative Na(+)/Cl(-)-dependent
      neurotransmitter/osmolyte transporter inebriated (ine) is expressed in the
      basolateral membrane of anterior hindgut epithelial cells. This was confirmed by
      comparison with a known basolateral localized protein, the alpha subunit of Na(+)
      K(+) ATPase (ATPalpha). Under external hypertonicity, loss of ine in the hindgut
      epithelium results in severe dehydration without damage to the hindgut epithelial
      cells, implicating a physiological failure of water conservation/absorption. We
      also found that hindgut expression of ine is required for water conservation
      under desiccating conditions. Importantly, specific expression of ine in the
      hindgut epithelium can completely restore disrupted systemic water homeostasis in
      ine mutants under both conditions. Therefore, ine in the Drosophila hindgut is
      essential for the maintenance of systemic water homeostasis. 

PMID- 25613131
TI  - Characterization of HBV Among HBV/HIV-1 Co-Infected Injecting Drug Users from
      Mombasa, Kenya.
AB  - BACKGROUND: Hepatitis B (HBV) and Human Immunodeficiency virus (HIV) are both
      bloodborne viruses. Markers of either active or past HBV infection are present in
      many HIV infected patients. Worldwide, HBV prevalence varies geographically and
      endemicity is classified as low (<2%) or high (>8%). Genotypically, prevalence
      varies among different populations, with genotype A having a wide distribution.
      In Kenya, the prevalence of HIV-1/HBV co-infection ranges from 6-53% depending on
      the sub-population, with genotype A as the most common. OBJECTIVE: To determine
      the prevalence and characterize HBV in HBV/HIV co-infected injecting drug users
      (IDUs) from Mombasa, Kenya. METHODS: Blood samples were collected from HIV
      infected IDUs in Mombasa, Kenya. Hepatitis B surface antigen (HBsAg) was tested
      by enzyme immunoassay (EIA). HBV DNA was extracted by SMITEST R&D kit. Polymerase
      chain reaction (PCR) was done; followed by population sequencing of HBV preS,
      core and full genome using specific primers. Analysis was done phylogenetically
      with reference sequences from the Genbank. RESULTS: Seventy two HIV-positive
      samples were collected from IDUs in Mombasa in February and March 2010. Of these,
      10 (13.89%) were HBsAg-positive by EIA. Nine of the 10 samples (12.5%) were PCR
      positive for HBV in the preS region; from these, four HBV full length sequences
      were obtained. Phylogenetic analysis showed that all belonged to genotype A1.
      CONCLUSION: The prevalence of HBV co-infection among HIV-infected IDUs in
      Mombasa, Kenya was 12.5%. Phylogenetically, sequences obtained from this study
      showed clusters that were distinct from reported Kenyan reference sequences from
      the Genbank. The findings point to an existence of a transmission network among
      IDUs in Mombasa. This further suggests that HBV genotypes in Kenya may be
      regionally diverse.

PMID- 25613132
TI  - Improved Performance of COBAS AmpliPrep/COBAS TaqMan Version 2.0 Assay Over
      Amplicor Monitor Version 1.5 in the Quantification of HIV-1 RNA Viral Load in
      Abuja, Nigeria.
AB  - BACKGROUND: Improved viral detections by the real time PCR over the manual assays
      have been reported by various manufacturers. However, discrepancies and
      discordance between different platforms targeting the same pathogen have also
      been observed at different settings. METHODS: We used an analytical study design
      to compare the performance of the Cobas Taqman /Cobas Ampliprep version 2.0
      against the standard Amplicor Monitor 1.5 using 200 routine clinical samples, in
      Abuja- Nigeria. RESULTS: Taqman and Amplicor detected 118/200 (59%) and 83/200
      (41.5%) samples respectively. Two of 83 samples (2.4%) undetectable by Cobas
      Taqman, were detectable by Roche Amplicor, while 5 of 37 samples (13.5%) which
      were undetectable by Amplicor using Taqman. Among the 81 detectable samples by
      both assays 4 samples (4.9%) had a log10 difference > 0.5 log copies, while 9
      samples (11.1%) showed a wider discrepancy of >1 log10. Bland and Altman's
      comparison shows no significant difference between the two methods (p=0.2825) and
      CI-0.06171 to 0.2087. CONCLUSION: We observed a remarkable improvement in the
      performance of COBAS AmpliPrep/COBAS TaqMan version 2.0 Assay over Amplicor
      Monitor version 1.5 in the quantification of HIV1 RNA viral load. Discrepancies
      of clinical significance, in the viral load between the two platforms were also
      recorded. The implications of the inability of the automated Taqman 2.0 to detect
      2.4% of samples detectable by the Amplicor need to be considered by programs,
      clinicians and the manufacturers. Periodic evaluation of platforms to detect new
      circulating HIV subtypes within each locality is also recommended.

PMID- 25613133
TI  - Didehydro-cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and
      prevents potentiation of cocaine reward in Tat transgenic mice.
AB  - HIV-1 Tat protein has been shown to have a crucial role in HIV-1-associated
      neurocognitive disorders (HAND), which includes a group of syndromes ranging from
      undetectable neurocognitive impairment to dementia. The abuse of
      psychostimulants, such as cocaine, by HIV infected individuals, may accelerate
      and intensify neurological damage. On the other hand, exposure to Tat potentiates
      cocaine-mediated reward mechanisms, which further promotes HAND. Here, we show
      that didehydro-Cortistatin A (dCA), an analog of a natural steroidal alkaloid,
      crosses the blood-brain barrier, cross-neutralizes Tat activity from several HIV
      1 clades and decreases Tat uptake by glial cell lines. In addition, dCA potently
      inhibits Tat mediated dysregulation of IL-1beta, TNF-alpha and MCP-1, key
      neuroinflammatory signaling proteins. Importantly, using a mouse model where
      doxycycline induces Tat expression, we demonstrate that dCA reverses the
      potentiation of cocaine-mediated reward. Our results suggest that adding a Tat
      inhibitor, such as dCA, to current antiretroviral therapy may reduce HIV-1
      related neuropathogenesis. 

PMID- 25613134
TI  - STAT3 and its phosphorylation are involved in HIV-1 Tat-induced transactivation
      of glial fibrillary acidic protein.
AB  - Human immunodeficiency virus type 1 (HIV-1) Tat protein is a major pathogenic
      factor in HIV-associated neurological diseases; it exhibits direct neurotoxicity
      and indirect astrocyte-mediated neurotoxicity. We have shown that Tat alone is
      capable of activating glial fibrillary acidic protein (GFAP) expression and
      inducing astrocytosis involving sequential activation of early growth response
      protein 1 (Egr-1) and p300. In this study, we determined the roles of signal
      transducer and activator of transcription 3 (STAT3) in Tat-induced GFAP
      transactivation. STAT3 expression and phosphorylation led to significant
      increases in GFAP transcription and protein expression. Tat expression was
      associated with increased STAT3 expression and phosphorylation in Tat-expressing
      astrocytes and HIV-infected astrocytes. GFAP, Egr-1 and p300 transcription and
      protein expression all showed positive response to STAT3 and its phosphorylation.
      Importantly, knockdown of STAT3 resulted in significant decreases in Tat-induced
      GFAP and Egr-1 transcription and protein expression. Taken together, these
      findings show that STAT3 is involved in and acts upstream of Egr1 and p300 in the
      Tat-induced GFAP transactivation cascade and suggest important roles of STAT3 in
      controlling astrocyte proliferation and activation in the HIV-infected central
      nervous system. 

PMID- 25613137
TI  - Estrous cycle and HIV-1 Tat protein influence cocaine-conditioned place
      preference and induced locomotion of female mice.
AB  - The HIV-1 trans-activator of transcription (Tat) protein, interacts with
      psychostimulants to potentiate cocaine-reward in rodents. Sex steroids may
      protect against Tat-induced deficits. Female GT-tg transgenic mice conditionally
      expressed Tat protein targeted to brain via a doxycycline-dependent, GFAP-linked
      promoter. Mice were tested for cocaine-conditioned place preference (CPP) and
      cocaine-induced locomotion when in the proestrous (high-hormone) or diestrous
      (low-hormone) phases of their estrous cycle. Cocaine-CPP was potentiated by Tat
      induction via 50, 100, or 125 (but not 25) mg/kg doxycycline daily treatment for
      7 days. Diestrous mice exposed to Tat protein demonstrated significantly greater
      cocaine-CPP than did proestrous mice. Tat induction interacted with estrous cycle
      to decrease acute cocaine-induced locomotion among Tat-induced diestrous mice,
      but not their uninduced or proestrous counterparts, and attenuated cocaine
      sensitization. In a cocaine-challenge, previously cocaine-sensitized mice
      demonstrated greater cocaine-locomotion over cocaine-naive counterparts and Tat
      induction attenuated locomotion. Altogether, data demonstrate Tat and circulating
      sex steroid influences over cocaine-reward and psychostimulation. 

PMID- 25613136
TI  - HIV-1 Tat-induced changes in synaptically-driven network activity adapt during
      prolonged exposure.
AB  - HIV-associated neurocognitive disorders (HAND) afflict approximately half of HIV
      infected patients. The HIV-1 transactivator of transcription (Tat) protein is
      released by infected cells and contributes to the pathogenesis of HAND, but many
      of the underlying mechanisms remain poorly understood. Here we used fura-2-based
      Ca(2+) imaging and whole-cell patch-clamp recording to study the effects of Tat
      on the spontaneous synaptic activity that occurs in networked rat hippocampal
      neurons in culture. Tat triggered aberrant network activity that exhibited a
      decrease in the frequency of spontaneous action potential bursts and Ca(2+)
      spikes with a simultaneous increase in burst duration and Ca(2+) spike amplitude.
      These network changes were apparent after 4 h treatment with Tat and required the
      low-density lipoprotein receptor-related protein (LRP). Interestingly, Tat
      induced changes in network activity adapted during 24 h exposure. The activity
      returned to control levels in the maintained presence of Tat for 24 h. These
      observations indicate that Tat causes aberrant network activity, which is
      dependent on LRP, and adapts following prolonged exposure. Changes in network
      excitability may contribute to Tat-induced neurotoxicity in vitro and seizure
      disorders in vivo. Adaptation of neural networks may be a neuroprotective
      response to the sustained presence of the neurotoxic protein Tat and could
      underlie the behavioral and electrophysiological changes observed in HAND.

PMID- 25613140
TI  - The content, format and timing of a preparation for childhood hospitalization
      booklet: An action research project.
AB  - The experience of childhood hospitalization may be improved by appropriate
      preparation. As part of a larger project to improve preparation practices for
      children and their families, a group of health-care professionals investigated
      the content, format and timing of a pre-existing preparation booklet for a
      particular procedure. This article analyses the evaluation of the preparation
      booklet that led to a finding that collaboration among health-care professionals
      enables improved practice and shared professional power and responsibility.

PMID- 25613138
TI  - HIV-1 subtypes B and C Tat differentially impact synaptic plasticity expression
      and implicates HIV-associated neurocognitive disorders.
AB  - Earlier studies have established that infection with HIV-1 subtypes (clades)
      might differentially influence the neuropathogenesis of HIV-1-associated
      neurocognitive dysfunction (HAND). HIV-1 Trans activator of transcription protein
      (Tat) is of considerable significance and plays a major role in the central
      nervous system (CNS) dysfunction. However, these HIV-1 clades exert diverse
      cellular effects that leads to neuropathogenic dysfunction has not been well
      established. We hypothesized that the HIV-1 clade B and clade C Tat proteins
      effect synaptic plasticity expression in neuroblastoma cells (SK-N-MC) by diverse
      methods, and accordingly modulates the development of HAND. In the present study,
      we have analyzed important and highly expressed 84 key human synaptic plasticity
      genes expression which differentially impact in clade B and clade C Tat treated
      SK-N-MC cells using RT(2) Profile PCR Array human Synaptic Plasticity kit.
      Observed results demonstrate that out of 84 key synaptic plasticity genes, 36 and
      25 synaptic genes were substantially (>=3 fold) up-regulated and 5 and 5 genes
      considerably (>=3 fold) down-regulated in clade B and clade C Tat treated cells,
      respectively, compared to the control SK-N-MC. We have also estimated the levels
      of glutamine and glutamate in HIV-1 clade B and C Tat exposed SK-N-MC cells
      compared to untreated cells. Our results indicate that levels of glutamate,
      glutamine and expression of synaptic plasticity genes were highly dysregulated by
      HIV-1 clade B Tat compared to clade C Tat in SK-N-MC cells. In summary, this
      study suggests that clade B Tat substantially potentiates neuronal toxicity and
      further dysregulated synaptic plasticity genes in SK-N-MC may contribute to the
      severe neuropathogenesis linked with HAND.

PMID- 25613139
TI  - Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat
      induced neuronal injury.
AB  - HIV-1 infected individuals live longer but experience a prevalence rate of over
      50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective
      treatment is available. Viral and cellular factors secreted by HIV-1 infected
      cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the
      pathogenesis of HAND. Here we tested the hypothesis that creatine protected
      against HIV-1 Tat-induced neuronal injury by preventing mitochondrial
      bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat(1-72)
      induced increases in neuron cell death and synaptic area loss. Creatine protected
      against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat
      increased cellular levels of creatine, and creatine plus HIV-1 Tat further
      decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1
      Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced
      mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability
      transition pore opening. Thus, creatine may be a useful adjunctive therapy
      against HAND.

PMID- 25613142
TI  - [Editorial].

PMID- 25613141
TI  - Orofacial pain and symptoms of temporomandibular disorders in Finnish and Thai
      populations.
AB  - OBJECTIVE: Cultural or ethnic factors may play an important role in subjects'
      pain reports. The aim of the study was to compare the prevalence of orofacial
      pain symptoms between Finnish and Thai populations. MATERIALS AND METHODS: The
      Finnish study population comprised the Northern Finland Birth Cohort 1966, of
      which 5696 subjects participated in the present study. The Thai sample consisted
      of 1501 randomly selected people living in 10 different districts in Bangkok.
      Data on orofacial pain was collected based on questionnaires. RESULTS: After
      adjusting for age, gender and education, the logistic regression analysis showed
      that Thai subjects had an increased risk for reporting oral pain (OR = 4.5, 95%
      CI = 3.7-5.4), tooth pain (OR = 2.0, 95% CI = 1.8-2.4) and pain in the face (OR =
      1.5, 95% CI = 1.2-1.7). CONCLUSIONS: It can be concluded that Thai people report
      more orofacial pain symptoms than Finnish subjects. Cross-cultural factors exist
      in the background of reporting pain symptoms in the oral and facial area.

PMID- 25613135
TI  - HIV-1 proteins, Tat and gp120, target the developing dopamine system.
AB  - In 2014, 3.2 million children (< 15 years of age) were estimated to be living
      with HIV and AIDS worldwide, with the 240,000 newly infected children in the past
      year, i.e., another child infected approximately every two minutes [1]. The
      primary mode of HIV infection is through mother-to-child transmission (MTCT),
      occurring either in utero, intrapartum, or during breastfeeding. The effects of
      HIV-1 on the central nervous system (CNS) are putatively accepted to be mediated,
      in part, via viral proteins, such as Tat and gp120. The current review focuses on
      the targets of HIV-1 proteins during the development of the dopamine (DA) system,
      which appears to be specifically susceptible in HIV-1-infected children.
      Collectively, the data suggest that the DA system is a clinically relevant target
      in chronic HIV-1 infection, is one of the major targets in pediatric HIV-1 CNS
      infection, and may be specifically susceptible during development. The present
      review discusses the development of the DA system, follows the possible targets
      of the HIV-1 proteins during the development of the DA system, and suggests
      potential therapeutic approaches. By coupling our growing understanding of the
      development of the CNS with the pronounced age-related differences in disease
      progression, new light may be shed on the neurological and neurocognitive
      deficits that follow HIV-1 infection. 

PMID- 25613143
TI  - Avoiding the use of a femoral bridging catheter using a two-stage Hemodialysis
      Reliable Outflow (HeRO) graft implantation technique.
AB  - PURPOSE: To evaluate a two-stage Hemodialysis Reliable Outflow (HeRO)
      implantation technique that avoids the use of a femoral bridging catheter versus
      the conventional one-stage technique requiring a bridging catheter in selected
      patients. METHODS: A retrospective review was performed on 20 end-stage renal
      disease patients with an internal jugular vein (IJV) catheter selected for two
      stage HeRO implantation at our institution between January 2010 and March 2013.
      The arterial graft component (AGC) was implanted without anastomosing it to the
      target artery (first stage). After AGC incorporation, the venous outflow
      component was inserted (second stage). The preexisting IJV catheter was
      maintained for hemodialysis access during the interstage period. Patient
      characteristics, patency using Kaplan-Meier method and infection rates were
      analyzed. RESULTS: A total of 17 patients with a mean age of 59 years (70.6%
      women) completed the two-stage procedure. During the interstage period (mean 12
      weeks, range 4-22 weeks), no graft- or surgery-related infection occurred. The
      need of a femoral bridging catheter was avoided by utilizing the preexisting IJV
      dialysis catheter. The accumulated HeRO days were 3,916 days with a mean follow
      up of 7.7 months (range 1-22.6 months). The HeRO-related infection rate was
      0.3/1,000 days. The primary assisted and secondary patency rates at 6 months were
      69% and 82%, respectively, which were similar to those of arteriovenous grafts.
      Staging conferred immediate vascular accessibility. CONCLUSIONS: Avoiding the use
      of a femoral bridging catheter using the two-stage technique may lower infection
      rate, with comparable primary assisted and secondary patency to arteriovenous
      grafts and added benefit of immediate cannulatability in this subset of patients.

PMID- 25613144
TI  - Primary intraoperative transluminal angioplasty: a new approach to reduce the
      early failure of distal arteriovenous fistulas.
AB  - PURPOSE: About 8 years ago, we approached an intraoperative transluminal
      angioplasty (ITA) performed during the arteriovenous fistula (AVF) creation, to
      treat arterial or venous stenosis diagnosed by a preliminary ultrasound
      examination. Objective of this study is to validate the efficacy of ITA. METHODS:
      Early failure (EF) and failure to mature (FTM) were evaluated in 69 AVFs with ITA
      created in 58 patients in the last 3 years. In the same period, 160 patients
      received 188 AVFs without ITA and were considered control group. Of the two
      groups, age, comorbid factors, sex, primary and secondary patency rate (PR) were
      also analysed. RESULTS: The two groups were homogeneous for gender and age (70.4
      + 11.1 years of ITA group vs. 66.3 + 14.4, p = 0.059). The incidence of diabetes,
      heart disease and peripheral artery disease was higher in the ITA group (43% vs.
      17%, p<0.0001, 35% vs. 6%, p<0.0001 and 56% vs. 15%, p<0.0001, respectively). EF
      and FTM occurred in seven and eight cases in the ITA group and in 15 and 13 cases
      in the controls, respectively. Total failure occurred in 24% of ITA group and 14%
      of the controls (p = 0.2). The primary PR at 6, 12 and 24 months was 78%, 72% and
      59% for ITA group and 85%, 78% and 78 % for control group (p<0.01). The secondary
      PR at 6, 12 and 24 months was 91%, 86% and 80% for ITA group and 95%, 95% and 92%
      for the controls (p<0.01). CONCLUSIONS: Our ITA approach has allowed satisfactory
      results in patients at a high risk of AVF failure.

PMID- 25613145
TI  - Modified MILLER banding procedure for managing high-flow access and dialysis
      associated steal syndrome.
AB  - PURPOSE: Both high-flow vascular access (VA) and dialysis-associated steal
      syndrome are serious complications requiring a flow reduction technique. We
      adopted the minimally invasive limited ligation endoluminal-assisted revision
      (MILLER) banding procedure with some modifications to control the high blood flow
      and steal syndrome during VA procedures and retrospectively assessed the outcome.
      METHODS: Seven patients with high-flow access (access flow >1400 ml/min) and five
      patients with steal syndrome (with pain, coldness, or cyanosis) were treated
      using the MILLER banding method. Flow volume of the brachial artery was monitored
      using Doppler ultrasonography during the banding procedure. In patients with
      steal syndrome, the finger probe of a pulse oximeter was attached to a finger on
      the ipsilateral side, and the peripheral oxygen saturation (SpO2) was monitored.
      RESULTS: In the high-flow group, the mean access blood flow (Qa) decreased from
      2043 +/- 463 ml/min (mean +/- SD) to 1248 +/- 388 ml/min (p<0.001). In the steal
      syndrome group, the SpO2 value improved in all steal syndrome patients after
      banding. Symptoms were almost relieved in two steal syndrome patients. The Qa in
      the steal group decreased from 997 +/- 867 to 548 +/- 376 ml/min (p = 0.12). The
      secondary patency rates of the high-flow and steal groups at 6 months were 83.3%
      and 50%, respectively. CONCLUSIONS: The MILLER banding procedure with
      intraoperative access flow monitoring is effective to treat high-flow VA and
      steal syndrome.

PMID- 25613147
TI  - Factors that predict increased catheter tip movement in left internal jugular
      vein implantable venous access ports upon standing.
AB  - PURPOSE: To determine the characteristics that predict catheter tip movement with
      positional changes in patients with left-sided, internal jugular vein (IJV)
      implantable venous access ports. METHODS: A retrospective review revealed 264
      patients with left IJV ports placed at one academic institution from 2008 to 2013
      with follow-up upright chest radiographs. Demographic information was recorded
      and anatomic measurements were made on both procedural fluoroscopic imaging and
      upright chest radiographs. Multivariate regression analysis was performed to
      determine which factors had statistically significant relationships with catheter
      tip movement distance. RESULTS: Mean catheter tip movement was 1.49 +/- 1.97 cm.
      There was a statistically significant positive relationship between catheter tip
      movement distance and age (p = 0.03), body mass index (BMI) (p = 0.02),
      innominate vein angle (p<0.01) and dual- compared to single-lumen ports (p =
      0.02). Port pocket location, venous access site and gender did not demonstrate
      statistical significance. CONCLUSIONS: The factors associated with increased
      positional catheter tip movement for left IJV ports include patient age, BMI,
      innominate vein angle and dual- vs single-lumen port. This information can be
      useful in determining initial placement position and avoiding complications
      associated with catheter malposition.

PMID- 25613146
TI  - Current use of ultrasound for central vascular access in children and infants in
      the Nordic countries--a cross-sectional study.
AB  - PURPOSE: The use of ultrasound (US) guidance for central vascular access in
      children has been advocated as a safer approach compared to traditional landmark
      techniques. We therefore collected data on the current use of US for central
      vascular access in children and infants in the Nordic countries. METHODS: A cross
      sectional survey using an online questionnaire was distributed to one
      anaesthesiologist at every hospital in the Nordic countries; a total of 177
      anaesthesiologists were contacted from July till August 2012. RESULTS: The use of
      US for placing central venous catheters (CVCs) seems widespread across the Nordic
      countries. Close to 80% of respondents were using it "almost always" or
      "frequently" across all paediatric age groups for internal jugular vein
      cannulation. US was least frequently used when catheterizing the subclavian vein.
      The two most common reasons given when not using US were lack of training
      followed by lack of equipment. We found no difference in the use of US between
      high-volume centres and low-volume centres. (High-volume centres placed
      paediatric CVCs at least weekly.). CONCLUSIONS: US was commonly used for
      cannulation of the internal jugular vein but infrequently for the subclavian
      vein. A lack of training seems to be a barrier for further increasing the use of
      US. Establishing standardized training programmes based on current evidence
      should alleviate this.

PMID- 25613149
TI  - Stacked functionalized silicene: a powerful system to adjust the electronic
      structure of silicene.
AB  - Herein, we employed first principle density functional periodic calculations to
      characterize the silicon counterpart of graphene:silicene. We found that silicene
      is far more reactive than graphene, very stable and strong Si-X bonds can be
      formed, where X = H, CH3, OH and F. The Si-F bond is the strongest one, with a
      binding energy of 114.9 kcal mol(-1). When radicals are agglomerated, the binding
      energy per functional grows up to 17 kcal mol(-1). The functionalization with OH
      radicals produces the largest alterations of the structure of silicene, due to
      the presence of intralayer hydrogen bonds. The covalent addition of H, CH3, OH
      and F to silicene enables the adjustment of its electronic structure. In effect,
      functionalized silicene can be a semiconductor or even exhibit metallic
      properties when the type and concentration of radicals are varied. The most
      interesting results were obtained when two layers of functionalized silicene were
      stacked, given that the band gaps experienced a significant reduction with
      respect to those computed for symmetrically and asymmetrically (Janus)
      functionalized monolayer silicenes. In the case of fluorine, the largest changes
      in the electronic structure of bilayer silicene were appreciated when at least
      one side of silicene was completely fluorinated. In general, the fluorinated side
      induces metallic properties in a large number of functionalized silicenes. In
      some cases which presented band gaps as large as 3.2 eV when isolated, the
      deposition over fluorinated silicene was able to close that gap and induce a
      metallic character. In addition to this, in four cases small gaps in the range of
      0.1-0.6 eV were obtained for bilayer silicenes. Therefore, functionalization of
      silicene is a powerful method to produce stable two-dimensional silicon based
      nanomaterials with tunable optical band gaps. 

PMID- 25613148
TI  - Proactive surveillance approach to guarantee a functional arteriovenous fistula
      at first dialysis is worth.
AB  - PURPOSE: To evaluate the impact of a proactive surveillance program on functional
      access rate at the time of first dialysis. METHODS: In January 2010, a proactive
      surveillance program to intercept failures to mature was set up at the University
      Hospitals Leuven. Patients receiving an arteriovenous fistula (AVF) for pre
      dialysis end-stage renal disease between January 2010 and May 2013 were
      retrospectively analyzed. The primary end-point was a functional AVF at first
      dialysis. Also, AVF- associated complications and reinterventions were analyzed.
      Furthermore, primary, assisted primary and secondary patency rates were estimated
      using Kaplan-Meier survival curves. RESULTS: One hundred sixty-four patients were
      included in the study. Patients were followed until first dialysis. Median follow
      up time was 287 days (interquartile range, 108-551 days). During follow-up, 40
      patients (24.4%) needed one or more additional interventions, resulting in 60
      reinterventions. Ten patients needed dialysis within the minimal accepted
      maturation period of the AVF (4 weeks). Of the 154 patients who could await the
      maturation period of the AVF, 145 (94.2%) appeared ready for use at the time of
      dialysis or at the end of the study period. In 34 of them (22%), this was thanks
      to one or more interventions during follow-up. CONCLUSIONS: A dedicated
      surveillance program of patients with AVFs in the pre-dialysis stadium detects
      failure to mature. Close coaching and proactive intervention can aid the patient
      in his own "fistula first" project.

PMID- 25613150
TI  - Tissue vascularization through 3D printing: Will technology bring us flow?
AB  - BACKGROUND: Though in vivo models provide the most physiologically relevant
      environment for studying tissue function, in vitro studies provide researchers
      with explicit control over experimental conditions and the potential to develop
      high throughput testing methods. In recent years, advancements in developmental
      biology research and imaging techniques have significantly improved our
      understanding of the processes involved in vascular development. However, the
      task of recreating the complex, multi-scale vasculature seen in in vivo systems
      remains elusive. RESULTS: 3D bioprinting offers a potential method to generate
      controlled vascular networks with hierarchical structure approaching that of in
      vivo networks. Bioprinting is an interdisciplinary field that relies on advances
      in 3D printing technology along with advances in imaging and computational
      modeling, which allow researchers to monitor cellular function and to better
      understand cellular environment within the printed tissue. CONCLUSIONS: As
      bioprinting technologies improve with regards to resolution, printing speed,
      available materials, and automation, 3D printing could be used to generate highly
      controlled vascularized tissues in a high throughput manner for use in
      regenerative medicine and the development of in vitro tissue models for research
      in developmental biology and vascular diseases.

PMID- 25613151
TI  - Effects of subcutaneous LPS injection on gestational length and intrauterine and
      neonatal mortality in mice.
AB  - BACKGROUND: Infection during pregnancy can predispose offspring to develop
      various psychiatric disorders such as depression in later life. In order to
      investigate the potential mechanisms underlying these associations, animal models
      of maternal infection have been employed. As such, lipopolysaccharide (LPS) has
      been commonly used to mimic a bacterial infection in pregnant mice. OBJECTIVE:
      The original aim of our study was to investigate the effects of different doses
      of subcutaneous LPS administration on affective behavior in adult mouse
      offspring. In the present paper, however, we report that subcutaneous LPS
      administration has a profound impact on gestational length, litter size, and
      perinatal mortality in the offspring, even at a relatively low dose. METHODS:
      Pregnant mice were randomly divided into 3 groups, receiving either a high (2
      mg/kg) or a low (0.5 mg/kg) dose of LPS or phosphate-buffered saline by means of
      subcutaneous injection. Subsequently, the effects on gestational length, litter
      size, and perinatal mortality in the offspring were assessed. RESULTS: After
      subcutaneous injection with a high dose of LPS, we observed a significant
      decrease in gestational length and an increase in neonatal mortality. When the
      low dose was administered, a tendency towards a reduced litter size was observed,
      most likely reflecting increased intrauterine mortality in response to prenatal
      maternal LPS exposure. CONCLUSIONS: We showed that subcutaneous administration of
      2 mg/kg LPS to pregnant mice in the last phase of gestation should be avoided
      because of high offspring mortality rates, whereas subcutaneous injection of 0.5
      mg/kg LPS seems to result in reabsorption of the fetuses.

PMID- 25613152
TI  - With Patient-reported Health Changing, Is It Time to Retool Our Instruments?

PMID- 25613154
TI  - EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract
      Symptoms including Benign Prostatic Obstruction.
AB  - CONTEXT: Lower urinary tract symptoms (LUTS) represent one of the most common
      clinical complaints in adult men and have multifactorial aetiology. OBJECTIVE: To
      develop European Association of Urology (EAU) guidelines on the assessment of men
      with non-neurogenic LUTS. EVIDENCE ACQUISITION: A structured literature search on
      the assessment of non-neurogenic male LUTS was conducted. Articles with the
      highest available level of evidence were selected. The Delphi technique consensus
      approach was used to develop the recommendations. EVIDENCE SYNTHESIS: As a
      routine part of the initial assessment of male LUTS, a medical history must be
      taken, a validated symptom score questionnaire with quality-of-life question(s)
      should be completed, a physical examination including digital rectal examination
      should be performed, urinalysis must be ordered, post-void residual urine (PVR)
      should be measured, and uroflowmetry may be performed. Micturition frequency
      volume charts or bladder diaries should be used to assess male LUTS with a
      prominent storage component or nocturia. Prostate-specific antigen (PSA) should
      be measured only if a diagnosis of prostate cancer will change the management or
      if PSA can assist in decision-making for patients at risk of symptom progression
      and complications. Renal function must be assessed if renal impairment is
      suspected from the history and clinical examination, if the patient has
      hydronephrosis, or when considering surgical treatment for male LUTS.
      Uroflowmetry should be performed before any treatment. Imaging of the upper
      urinary tract in men with LUTS should be performed in patients with large PVR,
      haematuria, or a history of urolithiasis. Imaging of the prostate should be
      performed if this assists in choosing the appropriate drug and when considering
      surgical treatment. Urethrocystoscopy should only be performed in men with LUTS
      to exclude suspected bladder or urethral pathology and/or before minimally
      invasive/surgical therapies if the findings may change treatment. Pressure-flow
      studies should be performed only in individual patients for specific indications
      before surgery or when evaluation of the pathophysiology underlying LUTS is
      warranted. CONCLUSIONS: These guidelines provide evidence-based practical
      guidance for assessment of non-neurogenic male LUTS. An extended version is
      available online (www.uroweb.org/guidelines). PATIENT SUMMARY: This article
      presents a short version of European Association of Urology guidelines for non
      neurogenic male lower urinary tract symptoms (LUTS). The recommended tests should
      be able to distinguish between uncomplicated male LUTS and possible differential
      diagnoses and to evaluate baseline parameters for treatment. The guidelines also
      define the clinical profile of patients to provide the best evidence-based care.
      An algorithm was developed to guide physicians in using appropriate diagnostic
      tests.

PMID- 25613153
TI  - Dehydrated Human Amnion/Chorion Membrane Allograft Nerve Wrap Around the
      Prostatic Neurovascular Bundle Accelerates Early Return to Continence and Potency
      Following Robot-assisted Radical Prostatectomy: Propensity Score-matched
      Analysis.
AB  - We present a propensity-matched analysis of patients undergoing placement of
      dehydrated human amnion/chorion membrane (dHACM) around the neurovascular bundle
      (NVB) during nerve-sparing (NS) robot-assisted laparoscopic prostatectomy (RARP).
      From March 2013 to July 2014, 58 patients who were preoperatively potent (Sexual
      Health Inventory for Men [SHIM] score >19) and continent (no pads) underwent full
      NS RARP. Postoperative outcomes were analyzed between propensity-matched graft
      and no-graft groups, including time to return to continence, potency, and
      biochemical recurrence. dHACM use was not associated with increased operative
      time or blood loss or negative oncologic outcomes (p>0.500). Continence at 8 wk
      returned in 81.0% of the dHACM group and 74.1% of the no-dHACM group (p=0.373).
      Mean time to continence was enhanced in group 1 patients (1.21 mo) versus (1.83
      mo; p=0.033). Potency at 8 wk returned in 65.5% of the dHACM patients and 51.7%
      of the no-dHACM group (p=0.132). Mean time to potency was enhanced in group 1,
      (1.34 mo), compared to group 2 (3.39 mo; p=0.007). Graft placement enhanced mean
      time to continence and potency. Postoperative SHIM scores were higher in the
      dHACM group at maximal follow-up (mean score 16.2 vs 9.1). dHACM allograft use
      appears to hasten the early return of continence and potency in patients
      following RARP. 

PMID- 25613155
TI  - [Veno-arterial extracorporeal membrane oxygenation support in a patient with
      right ventricular failure post- pulmonary endarterectomy surgery].

PMID- 25613156
TI  - Multifunctional assembly of micrometer-sized colloids for cell sorting.
AB  - Compared to the extensively studied nanometer-sized colloids, less attention has
      been paid to the assembly of micrometer-sized colloids with multifunctional
      characteristics. To address this need, a bottom-up approach is developed for
      constructing self-assemblies of micrometer-sized magnetic colloids possessing
      multifunctionality, including magnetic, optical, and biological activities.
      Biotinylated oligo (p-phenylene vinylene) (OPV) derivatives are designed to
      mediate the self-assembly of streptavidin-modified magnetic beads. The optical
      element OPV derivatives provide a fluorescence imaging ability for tracing the
      assembly process. Target cells can be recognized and assembled by the colloidal
      assembly with bioactive element antibodies. The colloidal assembly reveals better
      cell isolation performance by its amplified magnetic response in comparison to
      monodisperse colloids. The self-assembly of micrometer-sized magnetic colloids
      through a combination of different functional ingredients to realize
      multifunction is conceptually simple and easy to achieve. 

PMID- 25613158
TI  - Mesenchymal stem cells mitigate cirrhosis through BMP7.
AB  - BACKGROUND/AIMS: Transplantation of mesenchymal stem cells (MSCs) has therapeutic
      effects on various diseases, while its effect on developing cirrhosis as well as
      the underlying mechanism remained largely unknown. METHODS: Twenty C57BL/6 mice
      were randomly separated into 2 groups of ten each. One group received
      transplantation of MSCs, while the other group received saline as control. The
      mice then received intraperitoneal injection of carbon tetrachloride (CCl4) twice
      per week for 8 weeks to develop cirrhosis. After another 4 weeks, the levels of
      cirrhosis in these mice were evaluated by liver fibrosis area, portal pressure,
      sodium balance and excretion. Transcripts of transforming growth factor beta 1
      (TGFbeta1) and bone morphogenic protein 7 (BMP7) in the mouse livers were
      quantified by RT-qPCR. BMP7-depleted MSCs were prepared and applied in this
      model, and compared to MSCs. RESULTS: Liver fibrosis, portal hypertension and
      sodium retention that were developed by CCl4, were all significantly alleviated
      by MSCs transplantation, which decreased TGFbeta1 levels and increased BMP7
      levels in the injured liver. MSCs were found to express extremely high levels of
      BMP7. Knockdown of BMP7 in MSCs completely abolished the protective effect of
      MSCs against CCl4-induced cirrhosis. CONCLUSIONS: MSCs mitigate cirrhosis through
      their production of BMP7 against the fibrogenic effect of TGFbeta1 in the injured
      liver.

PMID- 25613159
TI  - Mass Spectrometry of Flame Figures.

PMID- 25613161
TI  - Outcome of planned home and hospital births among low-risk women in Iceland in
      2005-2009: a retrospective cohort study.
AB  - BACKGROUND: At 2.2 percent in 2012, the home birth rate in Iceland is the highest
      in the Nordic countries and has been rising rapidly in the new millennium. The
      objective of this study was to compare the outcomes of planned home births and
      planned hospital births in comparable low-risk groups in Iceland. METHODS: The
      study is a retrospective cohort study comparing the total population of 307
      planned home births in Iceland in 2005-2009 to a matched 1:3 sample of 921
      planned hospital births. Regression analysis, adjusted for confounding variables,
      was performed for the primary outcome variables. RESULTS: The rate of oxytocin
      augmentation, epidural analgesia, and postpartum hemorrhage was significantly
      lower when labor started as a planned home birth. Differences in the rates of
      other primary outcome variables were not significant. The home birth group had
      lower rates of operative birth and obstetric anal sphincter injury. The rate of 5
      minute Apgar score < 7 was the same in the home and hospital birth groups, but
      the home birth group had a higher rate of neonatal intensive care unit admission.
      Intervention and adverse outcome rates in both study groups, including transfer
      rates, were higher among primiparas than multiparas. Oxytocin augmentation,
      epidural analgesia, and postpartum hemorrhage rates were significantly
      interrelated. CONCLUSIONS: This study adds to the growing body of evidence that
      suggests that planned home birth for low-risk women is as safe as planned
      hospital birth.

PMID- 25613160
TI  - Genome-wide analysis of the R2R3-MYB transcription factor genes in Chinese
      cabbage (Brassica rapa ssp. pekinensis) reveals their stress and hormone
      responsive patterns.
AB  - BACKGROUND: The MYB superfamily is one of the most abundant transcription factor
      (TF) families in plants. MYB proteins include highly conserved N-terminal MYB
      repeats (1R, R2R3, 3R, and atypical) and various C-terminal sequences that confer
      extensive functions. However, the functions of most MYB genes are unknown, and
      have been little studied in Chinese cabbage. RESULTS: Here, we analyzed 256
      (55.2% of total MYBs) R2R3-MYB genes from Chinese cabbage (Brassica rapa ssp.
      pekinensis) and anchored them onto the 10 chromosomes and three subgenomes. The
      R2R3-, 3R- and atypical MYB proteins in Chinese cabbage formed 45 subgroups based
      on domain similarity and phylogenetic topology. Organization and syntenic
      analysis revealed the genomic distribution and collinear relationships of the
      R2R3-BrMYBs. Synonymous nucleotide substitution (Ka/Ks) analysis showed that the
      Chinese cabbage MYB DNA-binding domain is under strong purifying selection.
      Moreover, RNA-seq data revealed tissue-specific and distinct R2R3-BrMYB
      expression profiles, and quantitative real-time PCR (qPCR) analysis in leaves
      showed stress responsive expression and crosstalk with ABA-auxin signaling
      cascades. CONCLUSIONS: In this study, we identified the largest MYB gene family
      in plants to date. Our results indicate that members of this superfamily may be
      involved in plant development, stress responses and leaf senescence, highlighting
      their functional diversity.

PMID- 25613162
TI  - [Pneumorrhachis and spontaneous pneumomediastinum, asthmatic rare complication].

PMID- 25613163
TI  - Rottboellia yellow mottle virus is a distinct species within the genus
      Sobemovirus.
AB  - Once considered a tentative member of the genus Sobemovirus, rottboellia yellow
      mottle virus (RoMoV) was excluded from the latest species list of the ICTV after
      the discovery of imperata yellow mottle virus (IYMV), which resembles RoMoV in
      host range and geographic origin. Here, sequence analysis of the complete genome
      of RoMoV suggested that it should be considered a distinct species within the
      genus Sobemovirus. It has the highest sequence identity (55 %) to ryegrass mottle
      virus (RGMoV), whereas its sequence identity to IYMV is lower (44 %). In a
      phylogenetic tree, RoMoV clusters together with RGMoV and artemisia virus A
      (ArtVA), a dicot-infecting sobemovirus.

PMID- 25613164
TI  - Sequence determination of a satellite RNA isolated from Aspergillus foetidus.
AB  - Aspergillus foetidus virus (AfV) has at least two distinct particle types,
      designated as AfV-fast (F) and AfV-slow (S). AfV-S includes AfV-S1, a
      victorivirus; AfV-S2, an unclassified satellite RNA; and AfV-S3, a previously
      uncharacterized dsRNA element. Here, we describe the complete sequence of AfV-S3,
      which is a short non-coding RNA with no known homologs. AfV-S3 is predicted to
      form an extended secondary structure, shares a 5' terminus with AfV-S2, and is a
      satellite RNA possibly dependent on both AfV-S1 and AfV-S2. This work concludes
      the sequencing of the A. foetidus virome.

PMID- 25613165
TI  - Photorefraction estimates of refractive power varies with the ethnic origin of
      human eyes.
AB  - Eccentric infrared photorefraction is an attractive tool for measuring refractive
      errors of young children and uncooperative subjects, for it allows quick and non
      invasive acquisition of data from both eyes simultaneously over a reasonably
      large dioptric range. Accuracy of refraction in this technique depends on
      calibration of luminance slope formed across the pupil into diopters (defocus
      calibration factor). Commercial photorefractors, like the PowerRef 3TM used in
      this study, employ an universal defocus calibration factor from one population
      (Caucasian) to convert raw data of all populations. This study reports
      significantly larger defocus calibration factors of PowerRef 3TM in 132 East
      Asian, African and Indian eyes, relative to the machine's default calibration (p
      < 0.001). The calibration slope of 50 Indian eyes was over-estimated by 64 +/-
      11% (mean +/- 95%CI), vis-a-vis, retinoscopy (p < 0.001). The error reduced to ~6
      7% upon rescaling the data using a calibration factor specific for Indian eyes or
      to that individual (p > 0.9, relative to no over-estimation). Our results
      therefore strongly suggest the use of an ethnicity- or individual-specific
      defocus calibration factor for accurate estimation of refraction using
      photorefraction. Inaccurate refraction estimates due to calibration errors will
      otherwise severely undermine the advantages of this technique. 

PMID- 25613167
TI  - Adult-onset Still's disease-pathogenesis, clinical manifestations, and new
      treatment options.
AB  - Adult-onset Still's disease (AOSD), a systemic inflammatory disorder, is often
      considered a part of the spectrum of the better-known systemic-onset juvenile
      idiopathic arthritis, with later age onset. The diagnosis is primarily clinical
      and necessitates the exclusion of a wide range of mimicking disorders. AOSD is a
      heterogeneous entity, usually presenting with high fever, arthralgia, skin rash,
      lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations.
      The diagnosis is clinical and empirical, where patients are required to meet
      inclusion and exclusion criteria with negative immunoserological results. There
      are no clear-cut diagnostic radiological or laboratory signs. Complications of
      AOSD include transient pulmonary hypertension, macrophage activation syndrome,
      diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis.
      Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver
      function tests, and elevated acute-phase reactants (ESR, CRP, ferritin).
      Treatment consists of anti-inflammatory medications. Non-steroidal anti
      inflammatory drugs have limited efficacy, and corticosteroid therapy and disease
      modifying anti-rheumatic drugs are usually required. Recent advances have
      revealed a pivotal role of proinflammatory cytokines such as tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6, IL-8, and IL-18 in disease
      pathogenesis, giving rise to the development of novel targeted therapies aiming
      at optimal disease control. The review aims to summarize recent advances in
      pathophysiology and potential therapeutic strategies in AOSD.

PMID- 25613166
TI  - Myocardial ischemic protection in natural mammalian hibernation.
AB  - Hibernating myocardium is an important clinical syndrome protecting the heart
      with chronic myocardial ischemia, named for its assumed resemblance to
      hibernating mammals in winter. However, the effects of myocardial ischemic
      protection have never been studied in true mammalian hibernation, which is a
      unique strategy for surviving extreme winter environmental stress. The goal of
      this investigation was to test the hypothesis that ischemic stress may also be
      protected in woodchucks as they hibernate in winter. Myocardial infarction was
      induced by coronary occlusion followed by reperfusion in naturally hibernating
      woodchucks in winter with and without hibernation and in summer, when not
      hibernating. The ischemic area at risk was similar among groups. Myocardial
      infarction was significantly less in woodchucks in winter, whether hibernating or
      not, compared with summer, and was similar to that resulting after ischemic
      preconditioning. Whereas several genes were up or downregulated in both
      hibernating woodchuck and with ischemic preconditioning, one mechanism was unique
      to hibernation, i.e., activation of cAMP-response element binding protein (CREB).
      When CREB was upregulated in summer, it induced protection similar to that
      observed in the woodchuck heart in winter. The cardioprotection in hibernation
      was also mediated by endothelial nitric oxide synthase, rather than inducible
      nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to
      study cardioprotection for two major reasons: (1) powerful cardioprotection
      occurs naturally in winter months in the absence of any preconditioning stimuli,
      and (2) it resembles ischemic preconditioning, but with novel mechanisms, making
      this model potentially useful for clinical translation. 

PMID- 25613168
TI  - Physical activity and dementia: long-term follow-up study of adult twins.
AB  - INTRODUCTION: Physical activity is associated with a decreased occurrence of
      dementia. In twins, we investigated the effect of persistent physical activity in
      adulthood on mortality due to dementia. MATERIALS AND METHODS: Physical activity
      was queried in 1975 and 1981 from the members of the older Finnish Twin Cohort (n
      = 21,791), who were aged 24-60 years at the end of 1981. The subjects were
      divided into three categories according to the persistence of their vigorous
      physical activity. Dementia deaths were followed up to the end of 2011. RESULTS:
      During the 29-year follow-up, 353 subjects died of dementia. In individual-based
      analyses the age- and sex-adjusted hazard ratio (HR) was 0.65 (95% CI 0.43-0.98)
      for subjects partaking in vigorous physical activities in both 1975 and 1981
      compared to those who were inactive in both years. No significant change was
      observed after adjusting for potential confounding factors. The corresponding HR
      for within-pair comparisons of the less active twin versus the more active co
      twin was 0.48 (95% CI 0.17-1.32). The results for analyses of the volume of
      physical activity were inconclusive. CONCLUSIONS: Persistent vigorous leisure
      time physical activity protects from dementia, and the effect appears to remain
      after taking into account childhood environment.

PMID- 25613170
TI  - Idiopathic pulmonary fibrosis: an update.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of
      idiopathic interstitial pneumonia. The disease, which occurs primarily in middle
      aged and older adults, is thought to arise following an aberrant reparative
      response to alveolar epithelial cell injury characterized by secretion of
      excessive amounts of extracellular matrix components, resulting in scarring of
      the lung, architectural distortion, and irreversible loss of function. A complex
      interplay between environmental and host factors is thought to contribute to the
      development of the disease, although the cause of IPF remains elusive and its
      pathogenesis incompletely understood. Over the last decade, disease definition
      and diagnostic criteria have evolved significantly, and this has facilitated the
      design of a number of high-quality clinical trials evaluating novel therapeutic
      agents for IPF. This massive effort of the medical and industry community has led
      to the identification of two compounds (pirfenidone and nintedanib) able to
      reduce functional decline and disease progression. These promising results
      notwithstanding, IPF remains a major cause of morbidity and mortality and a
      largely unmet medical need. A real cure for this devastating disease has yet to
      emerge and will likely consist of a combination of drugs targeting the plethora
      of pathways potentially involved in disease pathogenesis.

PMID- 25613169
TI  - Pharmacologic therapies for idiopathic pulmonary fibrosis, past and future.
AB  - Idiopathic pulmonary fibrosis (IPF) is a severe, progressive fibrotic disease of
      the lung of unknown etiology that affects approximately 150,000 patients in the
      United States. It carries a median survival of two to three years, but clinical
      course can vary markedly from patient to patient. There has been no established
      treatment for IPF, but recent advances in coordinated clinical trials through
      groups such as IPFnet and academia-industry partnerships have allowed this
      relatively rare disease to be studied in much greater depth. Historically, the
      default therapy for IPF was a combination of prednisone, N-acetylcysteine, and
      azathioprine, but recent trials have shown that this regimen actually increases
      mortality. An enormous body of work in recent years, spanning the bench to the
      bedside, has radically altered our understanding of the molecular mechanisms
      underlying IPF. Newer modalities, particularly those involving monoclonal
      antibodies targeted at specific pathways known to contribute to the fibrotic
      process, have generated a great deal of excitement in the field, and recent
      clinical trials on therapies such as pirfenidone and nintedanib herald a new era
      in targeted IPF therapies. 

PMID- 25613171
TI  - Prognostic implications of intraventricular conduction delays in a general
      population: the Health 2000 Survey.
AB  - AIMS: We examined the prognostic impact of eight different intraventricular
      conduction delays (IVCD) in the standard electrocardiogram (ECG) in a community
      cohort. METHODS AND RESULTS: Data were collected from 6299 Finnish individuals.
      During a mean 8.2 years (interquartile range 8.1 to 8.3) of follow-up 640
      subjects died (10.2%); 277 (4.4%) were cardiovascular deaths. For both sexes, all
      cause and cardiovascular mortality was higher in subjects with IVCD than in those
      without. In Cox regression analysis after adjustment for age and gender, the
      hazard ratio for cardiovascular mortality for non-specific IVCD was 4.25 (95%
      confidence interval [CI] 1.95-9.26, P < 0.0001) and for left bundle branch block
      (LBBB) 2.11 (95% CI 1.31-3.41, P = 0.002). Right bundle branch block (RBBB) was
      not related to additional mortality, while incomplete RBBB (IRBBB) presented a
      hazard ratio of 2.24 (95% CI 1.064-4.77, P = 0.036). CONCLUSIONS: In the general
      population, non-specific IVCD, LBBB, and IRBBB were associated with increased
      relative risk for all-cause and cardiovascular mortality. RBBB did not have an
      impact on cardiovascular mortality either in subjects with or without previous
      heart disease.

PMID- 25613172
TI  - T-wave inversion and mortality risk.
AB  - OBJECTIVE: To investigate the predictive value of T-wave inversion (TWI) on
      routine electrocardiogram (ECG) for mortality in the general population with
      various risk groups in a prospective population-based follow-up study. Subjects.
      ECGs of a random population-based sample of 1814 men aged 42-60 years without
      coronary heart disease (CHD) at baseline. RESULTS: During an average follow-up of
      21 years, 685 deaths occurred. Of these deaths 174 were due to CHD and 278 to
      cardiovascular disease (CVD). There were 57 subjects with TWI. After adjusting
      for age, TWI was associated with an increased CHD mortality (relative risk (RR)
      4.10, 95% CI 2.26-7.41), CVD mortality (RR 3.47, 95% CI 2.09-5.78), and all-cause
      mortality (RR 2.07, 95% CI 1.37-3.12). After further adjustment for conventional
      risk factors, TWI remained statistically significant, predicting CHD mortality
      (RR 2.62, 95% CI 1.57-4.36), CVD mortality (RR 2.18, 95% CI 1.40-3.38), and all
      cause mortality (RR 1.41, 95% CI 1.00-2.01), respectively. CONCLUSION: TWI is a
      strong predictor for CHD, CVD, and all-cause mortality in the general population.
      The respective risks of CHD and CVD among men with TWI were also increased among
      men with high blood pressure, LDL cholesterol, and obesity.

PMID- 25613173
TI  - Chemical composition of the endocarps of fruits of Styrax officinalis L.
AB  - Endocarps of fruits of Styrax officinalis L. have been subjected to a
      phytochemical investigation. Five compounds, americanin A (1), egonololeat (2),
      egonol-2'''-metil butanoat (3), egonolgentiobiside (4) and homoegonolgentiobiside
      (5) were isolated. Their structures were elucidated by using spectroscopic
      methods and comparison with the literature data. This is the first report of the
      presence of compound 1 and compound 2 in the genus Styrax (Styracaceae family)
      and S. officinalis L. species, respectively. 

PMID- 25613174
TI  - Evaluation of the therapeutic effects of conditioned media from mesenchymal stem
      cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model.
AB  - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined as an exposed
      necrotic bone in the oral cavity that does not heal after appropriate
      intervention for >8weeks with present or previous bisphosphonate treatment in the
      absence of radiotherapy. Until now, although several risk factors, including
      invasive dental procedures, infection, mechanical trauma to the jawbone, and
      concomitant use of immunosuppressive and chemotherapy drugs have been implicated
      in the etiology of BRONJ, its underlying mechanisms and treatments remain largely
      unknown. A study recently showed that intravenous administration of mesenchymal
      stem cells (MSCs) improved BRONJ, and it was hypothesized that paracrine effects
      by secretomes from MSCs are the main constituent. Here we used rat BRONJ models
      to examine the therapeutic effects with serum-free conditioned media from human
      MSCs (MSC-CM), including various secretomes. We showed that MSC-CM has protected
      rat MSCs and rat osteoclasts. MSC-CM enhanced the expression of osteogenic
      related genes and neovascularization-related genes by real-time reverse
      transcriptase polymerase chain reaction analysis in in vitro study. In in vivo
      study, 5-week-old Wistar/ST male rats received zoledronate (35MUg/kg/week) and
      dexamethasone (1mg/kg/day) subcutaneously for 2weeks. Unilateral maxillary molars
      were then extracted. Two weeks later, rats were divided into non-treatment, serum
      free Dulbecco's modified Eagle's medium, and MSC-CM groups. In the MSC-CM group,
      the open alveolar sockets in 63% of the rats with BRONJ healed with complete soft
      tissue coverage and socket bones, whereas the exposed necrotic bone with inflamed
      soft tissue remained in the other groups. Histological analysis showed new bone
      formation and the appearance of osteoclasts in the MSC-CM group. Osteoclasts were
      significantly reduced in the non-treatment group. Thus, we concluded that the
      antiapoptotic and antiinflammatory effects of MSC-CM dramatically regulated the
      turnover of local bone and indicated therapeutic effects on BRONJ. 

PMID- 25613175
TI  - Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft
      tissue-derived input functions to differentiate site-specific changes in bone
      metabolism in vivo.
AB  - The turnover of bone is a tightly regulated process between bone formation and
      resorption to ensure skeletal homeostasis. This process differs between bone
      types, with trabecular bone often associated with higher turnover than cortical
      bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in
      structure and mineral content, but are limited in the study of metabolic activity
      at a single time point, while analyses of serum markers can reveal changes in
      bone metabolism, but cannot delineate the origin of any aberrant findings. To
      obtain a site-specific assessment of bone metabolic status, bisphosphonate
      binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we
      show that early binding kinetics monitored in vivo using fluorescent molecular
      tomography (FMT) can monitor changes in bone metabolism in response to bone loss,
      stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the
      anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing
      different, metabolically distinct skeletal sites. Using time-lapse micro-CT,
      longitudinal bone turnover was quantified. The spine showed a significantly
      greater percent resorbing volume and surface in response to OVX, while mice
      treated with PTH showed significantly greater resorbing volume per bone surface
      in the spine and significantly greater forming surfaces in the knee. Correlation
      studies between binding kinetics and micro-CT suggest that forming surfaces, as
      assessed by time-lapse micro-CT, are preferentially reflected in the rate
      constant values while forming and resorbing bone volumes primarily affect plateau
      values. Additionally, we developed a blood pool correction method which now
      allows for quantitative multi-compartment analyses to be conducted using FMT.
      These results further expand our understanding of bisphosphonate binding and the
      use of bisphosphonate binding kinetics as a tool to monitor site-specific changes
      in bone metabolism in vivo. 

PMID- 25613177
TI  - Gastric electrical stimulation for obesity.
AB  - Obesity is a growing health problem worldwide with a major impact on health and
      healthcare expenditures. Medical therapy in the form of diet and pharmacotherapy
      has limited effect on weight. Standard bariatric surgery is effective but is
      associated with morbidity and mortality, creating an unmet need for alternative
      therapies. One such therapy, the application of electrical stimulation to the
      stomach, has been studied extensively for the last two decades. Though pulse
      parameters differ between the various techniques used, the rationale behind this
      assumes that application of electrical current can interfere with gastric motor
      function or modulate afferent signaling to the brain or both. Initial studies led
      by industry failed to show an effect on body weight. However, more recently,
      there has been a renewed interest in this therapeutic modality with a number of
      concepts being evaluated in large human trials. If successful, this minimally
      invasive and low-risk intervention would be an important addition to the existing
      menu of therapies for obesity.

PMID- 25613176
TI  - Endoscopic management of benign biliary strictures.
AB  - Benign biliary strictures are a common indication for endoscopic retrograde
      cholangiopancreatography (ERCP). Endoscopic management has evolved over the last
      2 decades as the current standard of care. The most common etiologies of
      strictures encountered are following surgery and those related to chronic
      pancreatitis. High-quality cross-sectional imaging provides a road map for
      endoscopic management. Currently, sequential placement of multiple plastic
      biliary stents represents the preferred approach. There is an increasing role for
      the treatment of these strictures using covered metal stents, but due to
      conflicting reports of efficacies as well as cost and complications, this
      approach should only be entertained following careful consideration. Optimal
      management of strictures is best achieved using a team approach with the surgeon
      and interventional radiologist playing an important role. 

PMID- 25613178
TI  - Endoscopic treatment of malignant biliary strictures.
AB  - Endoscopic stenting is a widely accepted strategy for providing effective
      drainage in both extrahepatic and intrahepatic malignant strictures. In patients
      with extrahepatic malignancies, uncovered self-expanding metal stents (SEMS)
      provide excellent palliation. Hilar malignancies are probably best palliated by
      placement of uncovered SEMS although some disagreement exists among experts
      regarding the type and number of stents for optimal palliation. Preoperative
      biliary drainage (PBD) is commonly performed although a higher risk of
      complications and the lack of clear benefit raise questions about this practice.
      Certain groups of patients such as those with markedly elevated bilirubin levels,
      and in those in whom neoadjuvant therapy is planned, are good candidates for PBD.
      Considerable controversy exists regarding the optimal method as well as type of
      stent for PBD in patients with hilar malignancies. Novel endoscopic therapies,
      including photodynamic therapy and radiofrequency ablation, have emerged as
      potential adjuvant therapies in the management of malignant bile duct strictures
      but need further long-term evaluation to establish survival benefit. This review
      focuses on the current status of endoscopic therapies for malignant biliary
      obstructions.

PMID- 25613179
TI  - Intestine and multivisceral transplantation: current status and future
      directions.
AB  - Intestinal failure and associated parenteral nutrition-induced liver failure
      cause significant morbidity, mortality, and health care burden. Intestine
      transplantation is now considered to be the standard of care in patients with
      intestinal failure who fail intestinal rehabilitation. Intestinal failure
      associated liver disease is an important sequela of intestinal failure, caused by
      parenteral lipids, requiring simultaneous liver-intestine transplant. Lipid
      minimization and, in recent years, the emergence of fish oil-based lipid
      emulsions have been shown to reverse parenteral nutrition-associated
      hyperbilirubinemia, but not fibrosis. Significant progress in surgical techniques
      and immunosuppression has led to improved outcomes after intestine
      transplantation. Intestine in varying combination with liver, stomach, and
      pancreas, also referred to as multivisceral transplantation, is performed for
      patients with intestinal failure along with liver disease, surgical abdominal
      catastrophes, neuroendocrine and slow-growing tumors, and complete
      portomesenteric thrombosis with cirrhosis of the liver. Although acute and
      chronic rejection are major problems, long-term survivors have excellent quality
      of life and remain free of parenteral nutrition.

PMID- 25613180
TI  - Biochanin A promotes proliferation that involves a feedback loop of microRNA-375
      and estrogen receptor alpha in breast cancer cells.
AB  - BACKGROUND: Biochanin A and formononetin are O-methylated isoflavones that are
      isolated from the root of Astragalus membranaceus, and have antitumorigenic
      effects. Our previous studies found that formononetin triggered growth-inhibitory
      and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and
      in vitro studies to further investigate the potential effect of biochanin A in
      promoting cell proliferation in estrogen receptor (ER)-positive cells, and to
      elucidate underlying mechanisms. METHODS: ERalpha-positive breast cancer cells
      (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry
      were used to assess cell proliferation and apoptosis. mRNA levels of ERalpha, Bcl
      2, and miR-375 were quantified using real-time polymerase chain reaction.
      Compared with the control, low biochanin A concentrations (2-6 MUM) stimulated
      ERalpha-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells
      were used to study the relevant signaling pathway. RESULTS: After treatment with
      biochanin A, ERalpha, miR-375, and Bcl-2 expression was significantly
      upregulated. Additionally, in the in vivo studies, uterine weight in
      ovariectomized mice treated with biochanin A increased significantly. CONCLUSION:
      This study demonstrated that biochanin A promoted ERalpha-positive cell
      proliferation through miR-375 activation and this mechanism is possibly involving
      in a miR-375 and ERalpha feedback loop.

PMID- 25613181
TI  - MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells.
AB  - Low-density lipoprotein receptor (LDLR) catalyzes the uptake of LDL-cholesterol
      by liver and peripheral organs. The function of the LDLR is antagonized by pro
      protein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR at the
      plasma membrane inducing LDLR degradation. Here, we report that matrix
      metalloproteinase-2 (MMP-2) interacts with and cleaves PCSK9, as evidenced by
      proteomic, chemical cross-linkage, blue native-PAGE and domain-specific
      antibodies Western blot analyses. Furthermore, MMP-2 overexpression renders Hepa1
      c1c7 cells resistant to PCSK9-induced LDLR degradation. The data suggest that
      pathological MMP-2 overexpression may protect the LDLR from PCSK-9-induced
      degradation. 

PMID- 25613182
TI  - Changes of dopamine transporter availability in depressed patients with and
      without anhedonia: a 123I-N-omega-fluoropropyl-carbomethoxy-3beta- (4
      Iodophenyl)tropane SPECT study.
AB  - BACKGROUND/AIMS: Dopamine is an important neurotransmitter involved in the
      pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play
      a crucial role in the pathophysiology of dopaminergic transmission. We
      investigated the relationship between striatal DAT availability and depression,
      pointing out possible correlations with anhedonia and treatment outcomes.
      METHODS: Ten depressed patients with anhedonia, 10 depressed patients without
      anhedonia and 20 healthy controls underwent single photon emission computed
      tomography using (123)I-FP-CIT [(123)I-N-omega-fluoropropyl-carbomethoxy-3beta-(4
      iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure
      Scale and the Hamilton Depression Rating Scale. A further assessment of DAT
      availability was performed in the 10 patients with marked anhedonia after a 3
      month pharmacological treatment. RESULTS: Depressed patients with and without
      anhedonia showed significantly lower (123)I-FP-CIT binding ratios in the
      bilateral striatum, caudate and putamen. No significant changes were detected
      after treatment in the 10 patients with marked anhedonia. When considering
      clinical outcomes, subjects with remission of depression showed a significant
      reduction of (123)I-FP-CIT binding ratios in all regions at baseline, but after
      treatment no differences were found any longer. CONCLUSIONS: We suppose that a
      hypofunction of the striatal dopaminergic system may be a 'state' feature of a
      depressive condition as a whole rather than anhedonia itself. On the other hand,
      some anhedonic features mainly represent an enduring trait that persists
      independently of mood state.

PMID- 25613184
TI  - Vertical habitat shift of viviparous and oviparous deep-sea cusk eels revealed by
      otolith microstructure and stable-isotope composition.
AB  - Otolith stable-oxygen-isotope composition and microstructure were analysed in
      order to investigate the vertical habitat shift of deep-sea cusk eels
      (Ophidiiformes). Otolith delta18 O profiles suggested that both viviparous blind
      cusk eels and oviparous cusk eels experienced a pelagic larval stage and then
      settled to the deep-sea floor over a vertical distance that ranged among
      individuals from 200 to >1000 m. This result shows that the larvae of viviparous
      Barathronus maculatus undertake an ontogenetic vertical migration after a period
      of larval drift that may facilitate their wide distribution on the sea floor.

PMID- 25613185
TI  - Comparison of recto-anal mucosal swab and faecal culture for the detection of
      Escherichia coli O157 and identification of super-shedding in a mob of Merino
      sheep.
AB  - We compared the use of recto-anal mucosal swab (RAMS) culture and faecal culture
      for the detection of E. coli O157 in a mob of Merino sheep. Fifty Merino wethers
      and maiden ewes housed in indoor pens were sampled on five occasions. We detected
      E coli O157 in 32% (16/50) of sheep, with weekly prevalence ranging from 4%
      (2/50) to 16% (8/50). Overall, 12.5% (2/16) were detected by RAMS culture only,
      and 37.5% (6/16) were detected by faecal culture only. The level of agreement
      between the two sampling methods was moderate [kappa statistic = 0.583, 95%
      confidence interval (CI) 0.460-0.707]. The relative sensitivities of RAMS and
      faecal culture were 67% (95% CI 41-86) and 57% (95% CI 34-77), respectively. We
      identified four super-shedding sheep using direct faecal culture. Although the
      majority of culture-positive sheep were detected at one sampling point only, 3/4
      super-shedding sheep were culture-positive at two sampling points, and 1/4 was
      culture-positive at four sampling points. Persistent culture positivity may
      indicate sheep that could be considered 'super-shedders' at some point. The use
      of immunomagnetic separation further improved the rate of detection of E. coli
      O157, which was isolated from 1/34 animals that were previously negative by
      enrichment culture alone. A significant difference between sampling weeks was
      detected for both faecal (P = 0.021) and RAMS (P = 0.006), with the prevalence at
      the mid-point of sampling (week 4) significantly (P < 0.05) higher than at the
      beginning or end of the study. Study conditions (penned sheep) might have been
      responsible for the high prevalence and the epidemic pattern of infection
      observed, and could serve as a future model for studies of E. coli O157
      transmission, shedding and super-shedding in sheep. 

PMID- 25613183
TI  - Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS?
AB  - Advancing research and clinical care, and conducting successful and cost
      effective clinical trials requires characterizing a given patient population. To
      gather a sufficiently large cohort of patients in rare diseases such as
      amyotrophic lateral sclerosis (ALS), we developed the Pooled Resource Open-Access
      ALS Clinical Trials (PRO-ACT) platform. The PRO-ACT database currently consists
      of >8600 ALS patient records from 17 completed clinical trials, and more trials
      are being incorporated. The database was launched in an open-access mode in
      December 2012; since then, >400 researchers from >40 countries have requested the
      data. This review gives an overview on the research enabled by this resource,
      through several examples of research already carried out with the goal of
      improving patient care and understanding the disease. These examples include
      predicting ALS progression, the simulation of future ALS clinical trials, the
      verification of previously proposed predictive features, the discovery of novel
      predictors of ALS progression and survival, the newly identified stratification
      of patients based on their disease progression profiles, and the development of
      tools for better clinical trial recruitment and monitoring. Results from these
      approaches clearly demonstrate the value of large datasets for developing a
      better understanding of ALS natural history, prognostic factors, patient
      stratification, and more. The increasing use by the community suggests that
      further analyses of the PRO-ACT database will continue to reveal more information
      about this disease that has for so long defied our understanding. 

PMID- 25613187
TI  - N-Doped carbon coated hollow Ni(x)Co(9-x)S8 urchins for a high performance
      supercapacitor.
AB  - N-doped carbon coated NixCo9-xS8 (NixCo9-xS8@C) hollow urchins have been
      synthesized via a two-step solvothermal synthesis and an in situ polymerization
      in dopamine together with a post-annealing process. The characterization
      indicated that NixCo9-xS8@C hollow urchins have urchin-like morphology and a
      uniform size distribution. Furthermore, there is a complete phrase transformation
      from the as obtained NiCo2S4/NixCo9-xS8 hybrid to NixCo9-xS8 during the thermal
      annealing process. More importantly, as electrochemical materials, NixCo9-xS8@C
      has a high specific capacitance (1404.0 F g(-1) at 2.0 A g(-1)) and excellent
      cycling performance (95.8% capacitance retention of the highest value after 2000
      cycles). These results can be attributed to the coating of N-doped carbon, which
      gives the composite good conductivity. Additionally, the phase transformation
      from NiCo2S4/NixCo9-xS8 to NixCo9-xS8 during the thermal annealing greatly
      enhanced the redox reaction of the Co and Ni species. 

PMID- 25613189
TI  - Assessing a conceptual model of over-the-counter medication misuse, adverse drug
      events and health-related quality of life in an elderly population.
AB  - AIM: The objectives of the present study were to test Spilker's quality of life
      model in the elderly population consuming over-the-counter (OTC) medications. It
      was hypothesized that OTC medication misuse increases adverse drug events (ADEs),
      ADEs as a result of OTC medication misuse decrease health-related quality of life
      (HRQoL) and the impact of OTC medication misuse on patients' HRQoL is fully
      medicated by ADEs associated with OTC medications. METHODS: Data were used from a
      previously carried out cross-sectional study using survey instruments with
      elderly patients consuming OTC medications in Houston, Texas, USA. The
      presence/absence of OTC misuse was assessed by an expert panel based on patient
      reported information on drug use characteristics; ADE was self-reported and HRQoL
      was measured using the Short Form-12v2, which contains a physical component
      summary score (PCS) and a mental component summary score (MCS). RESULTS: Of the
      154 respondents, 18.2% misused OTC medications and 22.1% reported ADE as a result
      of OTC medications. The mean +/- SD score of PCS and MCS was 40.6 +/- 6.8 and
      46.4 +/- 7, respectively. The hypothesized framework provided a well-fitted
      solution to the data (chi(2)  = 1.387, d.f. = 2, P = 0.49; weighted root mean
      square residual = 0.317). Misuse of OTC medications significantly increased ADEs
      associated with OTC medications (beta = 0.298) and increased ADEs significantly
      decreased patient reported PCS (beta = -0.312), but not MCS (beta = -0.213). OTC
      medication misuse indirectly decreased PCS and MCS by mediating the effect of an
      increase in ADE; however, the association was not statistically significant.
      CONCLUSIONS: Misuse of OTC medications is highly associated with ADEs. ADEs are
      capable of decreasing the physical health of elderly patients.

PMID- 25613188
TI  - Fumarate induces redox-dependent senescence by modifying glutathione metabolism.
AB  - Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH)
      are associated with a highly malignant form of renal cancer. We combined
      analytical chemistry and metabolic computational modelling to investigate the
      metabolic implications of FH loss in immortalized and primary mouse kidney cells.
      Here, we show that the accumulation of fumarate caused by the inactivation of FH
      leads to oxidative stress that is mediated by the formation of succinicGSH, a
      covalent adduct between fumarate and glutathione. Chronic succination of GSH,
      caused by the loss of FH, or by exogenous fumarate, leads to persistent oxidative
      stress and cellular senescence in vitro and in vivo. Importantly, the ablation of
      p21, a key mediator of senescence, in Fh1-deficient mice resulted in the
      transformation of benign renal cysts into a hyperplastic lesion, suggesting that
      fumarate-induced senescence needs to be bypassed for the initiation of renal
      cancers. 

PMID- 25613190
TI  - Neuropsychiatric symptoms in primary progressive aphasia and apraxia of speech.
AB  - AIM: To conduct a prospective analysis of the neuropsychiatric symptoms (NPS)
      across the three categories of primary progressive aphasia (PPA) and progressive
      apraxia of speech (PAOS), compare the prevalence and nature of the symptoms, and
      look at which symptoms could be helpful to better differentiate these PPA and
      PAOS categories. METHODS: A total of 106 consecutive patients with a diagnosis of
      semantic variant (n = 13), logopenic variant (n = 37), agrammatic variant (n =
      15) or PAOS (n = 41) were included in this prospective study. The NPS were
      measured by the Neuropsychiatric Inventory Questionnaire. RESULTS: There were 65
      patients with PPA and 41 with PAOS diagnosis. The most distinguishing features
      between the two groups were anxiety, apathy, aberrant motor behavior and
      appetite, while among the subtypes of PPA they were disinhibition and appetite
      changes. PPA and PAOS patients initially exhibited depression, but with increased
      disease duration, PAOS patients showed apathy (55.5%) while PPA patients showed
      disinhibition (28.6%) and aberrant motor behavior (14.3%). CONCLUSION: Mood
      symptoms like anxiety and appetite changes are more likely to be present at
      initial stages of PPA, whereas behavioral symptoms like aberrant motor behavior
      and apathy are likely to occur early in PAOS. The NPS seem to evolve with the
      progression of the disease in both PPA and PAOS.

PMID- 25613191
TI  - Understanding Mind/Body Medicine from Muslim Religious Practices of Salat and
      Dhikr.
AB  - There has been an increasing medical interest in Muslim religious practices in
      promoting well-being. Central to Muslim religious practices are salat (prayer)
      and dhikr (chanting). These two religious forms may be argued as comprising
      elements of mind/body medicine due to their positive effect on the
      psychoneuroimmunological response. The aim of this article was to further
      understand the mind/body aspects of Muslim salat and dhikr.

PMID- 25613192
TI  - Predicting Relationship of Smoking Behavior Among Male Saudi Arabian College
      Students Related to Their Religious Practice.
AB  - This study describes the relationships of smoking behavior among a sample of male
      college students in Kingdom of Saudi Arabia (KSA) to their religious practice,
      parents' smoking behaviors and attitudes, peers' smoking behaviors and attitudes,
      and knowledge about the dangers of smoking. A 49-item questionnaire was developed
      and pilot tested in KSA. This questionnaire was completed during the academic
      year 2013 by 715 undergraduate male students at the King Saud University in
      Riyadh. 29.8% of the students were smokers (13.8% cigarette smokers, 7.3% sheesha
      smokers, and 27% cigarette and sheesha smokers). Students in the College of
      Education were much more likely to be smokers than the students in the College of
      Science. The differences between the College of Education and the College of
      Science was statistically significant (chi (2) = 16.864. df = 1, p = .001).
      Logistic regression analysis suggested that students who were more faithful in
      their practice of Islam were 15% less likely to smoke. Students who were more
      knowledgeable about the dangers of smoking were 8% less likely to smoke. The
      logistic analysis identified peers (friends) as the most powerful factor in
      predicting smoking. The four-factor model had an overall classification accuracy
      of 78%. The need to understand more fully the dynamics of peer relations among
      Saudi Arabian males as a basis for developing tobacco education/prevention
      programs. Prevention programs will need to include education and changes in the
      college level or earlier in KSA.

PMID- 25613193
TI  - Immune responses associated with homologous protection conferred by commercial
      vaccines for control of avian pathogenic Escherichia coli in turkeys.
AB  - Avian pathogenic Escherichia coli (APEC) infections are a serious impediment to
      sustainable poultry production worldwide. Licensed vaccines are available, but
      the immunological basis of protection is ill-defined and a need exists to extend
      cross-serotype efficacy. Here, we analysed innate and adaptive responses induced
      by commercial vaccines in turkeys. Both a live-attenuated APEC O78 DeltaaroA
      vaccine (Poulvac(r) E. coli) and a formalin-inactivated APEC O78 bacterin
      conferred significant protection against homologous intra-airsac challenge in a
      model of acute colibacillosis. Analysis of expression levels of signature
      cytokine mRNAs indicated that both vaccines induced a predominantly Th2 response
      in the spleen. Both vaccines resulted in increased levels of serum O78-specific
      IgY detected by ELISA and significant splenocyte recall responses to soluble APEC
      antigens at post-vaccination and post-challenge periods. Supplementing a non
      adjuvanted inactivated vaccine with Th2-biasing (Titermax(r) Gold or aluminium
      hydroxide) or Th1-biasing (CASAC or CpG motifs) adjuvants, suggested that Th2
      biasing adjuvants may give more protection. However, all adjuvants tested
      augmented humoral responses and protection relative to controls. Our data
      highlight the importance of both cell-mediated and antibody responses in APEC
      vaccine-mediated protection toward the control of a key avian endemic disease. 

PMID- 25613194
TI  - The effect of oral 3,3'-diindolylmethane supplementation on the 2:16alpha-OHE
      ratio in BRCA1 mutation carriers.
AB  - Hormonal exposures are known to influence breast cancer risk among women with a
      BRCA1 mutation. Thus, dietary factors that increase the 2-hydroxyestrone
      (OHE):16alpha-OHE ratio, a biomarker inversely related to breast cancer
      development, may also influence cancer risk. We conducted a dietary intervention
      study to evaluate the ability of 300 mg/day of 3,3'-diindolylmethane (DIM) to
      increase the urinary 2:16alpha-OHE ratio in 20 women with a BRCA1 mutation. BRCA1
      mutation carriers (n = 15) were assigned to receive 300 mg/day of Rx Balance
      BioREsponse DIM for 4-6 weeks (intervention group) and five BRCA1 mutation
      carriers did not take DIM (control group). The urinary 2:16alpha-OHE ratio was
      assessed at baseline and after 4-6 weeks by immunoassay. There was no significant
      effect of DIM on the 2:16alpha-OHE ratio (2.4 at baseline vs. 3.0 after the
      intervention, P = 0.35). A short dietary intervention with DIM did not
      significantly increase the 2:16alpha-OHE ratio in female BRCA1 mutation carriers.
      Larger studies investigating the effect of dietary or lifestyle interventions on
      circulating hormone levels in these high-risk women are warranted.

PMID- 25613195
TI  - [Intracranial hemorrhage in three haemophilic adults: A severe complication of
      hemophilia].
AB  - BACKGROUND: Intracranial hemorrhage (ICH) complications are uncommon at
      hemophilic patients. OBSERVATIONS: We report three cases of ICH occurring in
      hemophilic patients. Contributing factors were identified in two patients:
      hemophilia severity, presence of inhibitor, hepatitis C virus infection, and high
      blood pressure. No contributing factor was identified in the last patient.
      CONCLUSION: Rapid diagnosis of ICH is crucial in hemophilic patients. A search
      for contributing factors, both those specific to hemophilia, and those favoring
      ICH in the general population, is essential to optimize therapeutic care.
      Specific substitutive treatment for the deficient factor is a difficult
      management challenge.

PMID- 25613196
TI  - Tear analysis as a tool to detect oligoclonal bands in radiologically isolated
      syndrome.
AB  - BACKGROUND: Although radiologically isolated syndrome (RIS) is a newly defined
      entity, incidental findings of T2 hypersignals on brain MRI can lead to
      misdiagnosis or useless investigations. The detection of oligoclonal bands (OCBs)
      in cerebrospinal fluid (CSF) is a major indicator that helps in diagnosis of
      subclinical inflammatory disease of the central nervous system, but lumbar
      puncture still remains an invasive option. METHODS: We have prospectively
      included patients with RIS, have compared the results of CSF and tear OCB
      detection by isoelectric focusing (IEF) and assessed concordance between OCB
      detection in tears and in CSF. Tears were collected using a Schirmer strip.
      RESULTS: In 45 recruited RIS patients, OCBs were detected in CSF for 55% (25/45)
      and in tears for 50% (21/42) of samples. CONCLUSIONS: We suggest that tear OCB
      detection may replace CSF OCB detection as a diagnostic tool in patients with RIS
      and be useful in follow-up.

PMID- 25613197
TI  - [Hypocomplementaemic urticarial vasculitis with bullous lesions and pericardial
      involvement].
AB  - BACKGROUND: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare
      disease involving urticarial cutaneous vasculitis, hypocomplementaemia and
      systemic manifestations. Pericardial involvement occurs in very rare cases. We
      report a case of HUVS associated with specific pericarditis and bullous lesions.
      PATIENTS AND METHODS: A 63-year-old woman consulted for chronic urticaria that
      had appeared ten months earlier. Her skin lesions were associated with weight
      loss of 10 kg, deterioration of respiratory function and abdominal pain.
      Leukocytoclastic vasculitis was seen in the skin biopsy sample.
      Hypocomplementaemia and anti C1q antibodies were present and a diagnosis of HUVS
      was made. During hospitalisation, extensive compressive pericardial effusion was
      identified, and histological examination of the biopsy revealed specific
      pericardial lymphocytic vasculitis. During follow-up, four episodes of infectious
      pneumonitis were noted. Bullous skin lesions were also observed. DISCUSSION: HUVS
      is a disease caused by an antibody against C1q complement responsible for
      urticarial lesions and vasculitis antibodies. To our knowledge, there have been
      only five reports in the literature of pericardial injury associated with HUVS.
      In our case, histological examination of the pericardium demonstrated lymphocytic
      vasculitis.

PMID- 25613198
TI  - [Prevention of skin cancer in "people of color": let's be clear!].

PMID- 25613200
TI  - Has the leaning tower of presumed health benefits from 'moderate' alcohol use
      finally collapsed?
AB  - The evolving epidemiological literature, including improved methodology for
      assessing causality in observational studies, is raising doubts about whether
      moderate alcohol consumption has a protective effect on health.

PMID- 25613199
TI  - The STOP-BANG questionnaire: reliability and validity of the Persian version in
      sleep clinic population.
AB  - PURPOSE: The snoring, tiredness, observed apnea, blood pressure, body mass index,
      age, neck circumference, gender (STOP-BANG) is a concise and effective
      obstructive sleep apnea (OSA) screening tool, part questionnaire (STOP), and part
      demographic or anthropometric measurements (BANG). The main purpose of this study
      was to translate this well-liked questionnaire into Persian and assess its
      reliability and validity in sleep clinic population. METHODS: Standard forward
      backward method was used for translation. A sample of 603 patients, who admitted
      to the sleep clinic, completely answered to the STOP questionnaire and underwent
      in-laboratory polysomnography, included in this study. Height, weight, and neck
      circumference were measured by technicians for calculating BANG score. The apnea
      hypopnea index (AHI) on the polysomnography was used as gold standard for OSA
      diagnosis: none (AHI < 5), mild (5 <= AHI < 15), moderate (15 <= AHI < 30), and
      severe (AHI >= 30). One hundred and forty one patients were answered to the STOP
      questionnaire twice at a time interval of 2-4 weeks for test-retest analysis.
      RESULTS: In reliability analysis, 124 (87.9 %) patients had same STOP score and
      130 (92.2 %) patients were classified in same risk of OSA. Based on the
      polysomnography, 438 patients (72.6 %) had mild (n = 124, 20.4 %), moderate (n =
      114, 18.9 %), and severe (n = 201, 33.3 %) OSA, whereas according to the STOP
      BANG, 502 patients (83.3 %) were at high risk of OSA. The sensitivity and
      specificity of the STOP-BANG were found to be 91.6 and 45.2 %, respectively, at
      AHI >= 5, 97.1 and 35.2 %, respectively, at AHI >= 15, and 98 and 29.4 %,
      respectively, at AHI >= 30. The area under the curve of the STOP-BANG for
      identifying mild, moderate, and severe OSA was 0.805, 0.779, and 0.755,
      respectively. CONCLUSIONS: Persian version of the STOP-BANG performs similar to
      its original version and is an easy-to-use questionnaire which could be
      considered as a reliable and valid tool for OSA screening.

PMID- 25613201
TI  - Imaging biomarkers in oncology: we can get more from what we see.

PMID- 25613202
TI  - Food and Drug Administration process for development and approval of drugs and
      radiopharmaceuticals: treatments in urologic oncology.
AB  - Regulatory advice and assessment play an important role in the successful
      development of new drugs and radiopharmaceuticals for the treatment of urologic
      malignancies. Cooperation between the US Food and Drug Administration (FDA) and
      the pharmaceutical industry has led to the approval of more than 20 new urologic
      oncology products in the last 2 decades. Despite these advances, more effective
      treatments need to be developed and approved for the treatment of urologic
      malignancies. This review provides general information about the FDA's role in
      the development of investigational new drugs, with an emphasis on the regulatory
      process and the requirements for marketing approval. In addition, this review
      summarizes the products for the treatment of urologic malignancies that were
      approved by the FDA in the last 30 years and the key issues concerning urologic
      oncology products that were discussed publicly at Oncologic Drug Advisory
      Committee meetings in the past 10 years.

PMID- 25613203
TI  - DNA buckling in bacteriophage cavities as a mechanism to aid virus assembly.
AB  - While relatively simple biologically, bacteriophages are sophisticated
      biochemical machines that execute a precise sequence of events during virus
      assembly, DNA packaging, and ejection. These stages of the viral life cycle
      require intricate coordination of viral components whose structures are being
      revealed by single molecule experiments and high resolution (cryo-electron
      microscopy) reconstructions. For example, during packaging, bacteriophages employ
      some of the strongest known molecular motors to package DNA against increasing
      pressure within the viral capsid shell. Located upstream of the motor is an
      elaborate portal system through which DNA is threaded. A high resolution
      reconstruction of the portal system for bacteriophage phi29 reveals that DNA
      buckles inside a small cavity under large compressive forces. In this study, we
      demonstrate that DNA can also buckle in other bacteriophages including T7 and
      P22. Using a computational rod model for DNA, we demonstrate that a DNA buckle
      can initiate and grow within the small confines of a cavity under biologically
      attainable force levels. The forces of DNA-cavity contact and DNA-DNA
      electrostatic repulsion ultimately limit cavity filling. Despite conforming to
      very different cavity geometries, the buckled DNA within T7 and P22 exhibits near
      equal volumetric energy density (~1kT/nm(3)) and energetic cost of packaging
      (~22kT). We hypothesize that a DNA buckle creates large forces on the cavity
      interior to signal the conformational changes to end packaging. In addition, a
      DNA buckle may help retain the genome prior to tail assembly through
      significantly increased contact area with the portal. 

PMID- 25613204
TI  - [In Process Citation].

PMID- 25613205
TI  - [In Process Citation].

PMID- 25613206
TI  - [In Process Citation].

PMID- 25613207
TI  - [In Process Citation].

PMID- 25613208
TI  - [Chronic salicylate poisoning is a challenging diagnosis].
AB  - Chronic salicylate poisoning is often seen in elderly patients as a result of an
      unintended overdosage, a change in metabolism or kidney function. The symptoms
      are often unspecific. This case report is about a 55-year-old man who was
      unconscious when admitted to hospital, and who died three hours after admission.
      An autopsy and a toxicological test showed a deadly level of salicylate in his
      blood. Afterwards, his wife told that he had complained about a sudden hearing
      loss, and that his behaviour had changed prior to his death. It is important to
      keep this diagnosis in mind when treating especially elderly patients. 

PMID- 25613209
TI  - [Anaphylactic shock after intradermal injection of corticosteroid].
AB  - Carboxymethylcellulose (CMC) is a derivative of cellulose found in many food
      products, pharmaceuticals and cosmetics. Allergy to CMC in parenteral
      corticosteroid preparations leading to anaphylaxis is rare, but has previously
      been reported. We report a case of a 52-year-old woman with prurigo nodularis of
      Hyde, who reacted with anaphylaxis after intradermal injection of Kenalog 40
      mg/ml. Allergy testing showed a positive skin prick test for CMC and the patient
      was advised to avoid future parenteral exposure to CMC. This case highlights the
      need to examine excipients in severe cases of drug allergy. 

PMID- 25613210
TI  - [Reversible tissue damage after paravasal infusion of oxaliplatin].
AB  - In this case report of a 62-year-old male with colon cancer receiving adjuvant
      chemotherapy extensive tissue damage was seen after oxaliplatin extravasation in
      the left antecubital region. Despite the severity and a prolonged stay in
      hospital he almost recovered 100% after eight months without surgery. High
      temperature and clinical signs of infection directed treatment into the use of
      several antibiotics of no avail. Recovery happened gradually after the onset of
      intensive physiotherapy including lymph drainage and the administration of
      prednisone. 

PMID- 25613211
TI  - [Diagnostic imaging and acute abdominal pain].
AB  - Acute abdominal pain is a common clinical condition. Clinical signs and symptoms
      can be difficult to interpret, and diagnostic imaging may help to identify intra
      abdominal disease. Conventional X-ray, ultrasound (US) and computed tomography
      (CT) of the abdomen vary in usability between common surgical causes of acute
      abdominal pain. Overall, conventional X-ray cannot confidently diagnose or rule
      out disease. US and CT are equally trustworthy for most diseases. US with
      subsequent CT may enhance diagnostic precision. Magnetic resonance seems
      promising for future use in acute abdominal imaging. 

PMID- 25613212
TI  - [Cross-sectorial cooperation has improved palliative care].
AB  - Project Palliation in the Odsherred Municipality is concerned with testing of a
      cooperation model between Lynghuset, general practice and Pain Centre, Holbaek
      Hospital. The purpose was to improve the palliative care to people suffering from
      life-threatening diseases through development of interdisciplinary and cross
      sectorial cooperation. The model has shown to contribute to improvements but it
      also leaves room for further qualification. 

PMID- 25613213
TI  - Release clinicians from the four walls of the hospital or practice.

PMID- 25613214
TI  - Single-Agent versus Combination Doxorubicin-Based Transarterial Chemoembolization
      in the Treatment of Hepatocellular Carcinoma: A Single-Blind, Randomized, Phase
      II Trial.
AB  - OBJECTIVES: It was the aim of this study to find an optimal therapeutic regimen
      of transarterial chemoembolization (TACE) by comparing the efficacy of
      chemoembolization with different anticancer agents in hepatocellular carcinoma
      (HCC) patients. METHODS: A single-blind, three-group parallel, randomized trial
      was conducted in Guangdong General Hospital, Guangzhou, China, with patients with
      biopsy-confirmed HCC. Group 1 received single-drug (doxorubicin)
      chemoembolization, while group 2 received double-drug (doxorubicin and mitomycin
      C) chemoembolization. Patients in group 3 were treated with triple-drug
      (doxorubicin, mitomycin C, and gemcitabine) chemoembolization. Lipiodol was used
      as embolization agent in all protocols. We compared the overall survival (OS),
      time to progression (TTP), and objective response rate (ORR) between groups.
      Response assessment was performed according to modified RECIST (Response
      Evaluation Criteria In Solid Tumors) criteria. RESULTS: Between January 2008 and
      January 2011, 162 patients (group 1, n = 50; group 2, n = 59; group 3, n = 53)
      were recruited. The OS and TTP in groups 1, 2, and 3 were 14.9 and 6.4, 13.2 and
      6.4, and 20.5 and 6.8 months, respectively. OS and TTP were statistically
      significant among groups (p = 0.002 and p = 0.037). The ORR was 22.0, 40.7, and
      56.6%, respectively. The ORR was significantly different across the three groups
      (p < 0.002). CONCLUSIONS: TACE with multiple chemotherapeutic agents might
      significantly increase survival and tumor response; additionally, gemcitabine was
      likely to have an advantage in improving the prognosis of HCC patients. (c) 2015
      S. Karger AG, Basel.

PMID- 25613215
TI  - The effects of acute alcohol on motor impairments in adolescent, adult, and aged
      rats.
AB  - Acute alcohol exposure has been shown to produce differential motor impairments
      between aged and adult rats and between adolescent and adult rats. However, the
      effects of acute alcohol exposure among adolescent, adult, and aged rats have yet
      to be systematically investigated within the same project using a dose-dependent
      analysis. We sought to determine the age- and dose-dependent effects of acute
      alcohol exposure on gross and coordinated motor performance across the rodent
      lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months)
      male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting
      reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a
      separate group of animals, blood ethanol concentrations (BEC) were determined at
      multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests
      were conducted with a Latin square repeated-measures design in which all animals
      received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3
      separate sessions via intraperitoneal (i.p.) injection. During testing, motor
      impairments were assessed on the RR 10 min post-injection and on ARR 20 min post
      injection. Aged animals spent significantly less time on the RR when administered
      1.0 g/kg alcohol compared to adult rats. In addition, motor performance
      impairments significantly increased with age after 2.0 g/kg alcohol
      administration. On the ARR test, aged rats were more sensitive to the effects of
      1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days
      after the last testing session, animals were given 3.0 g/kg alcohol and LORR was
      examined. During LORR, aged animals slept longer compared to adult and adolescent
      rats. This effect cannot be explained solely by BEC levels in aged rats. The
      present study suggests that acute alcohol exposure produces greater motor
      impairments in older rats when compared to adolescent and adult rats and begins
      to establish a procedure to determine motor effects by alcohol across the
      lifespan. 

PMID- 25613216
TI  - Effect of ammoniacal nitrogen on one-stage and two-stage anaerobic digestion of
      food waste.
AB  - This research compares the operation of one-stage and two-stage anaerobic
      continuously stirred tank reactor (CSTR) systems fed semi-continuously with food
      waste. The main purpose was to investigate the effects of ammoniacal nitrogen on
      the anaerobic digestion process. The two-stage system gave more reliable
      operation compared to one-stage due to: (i) a better pH self-adjusting capacity;
      (ii) a higher resistance to organic loading shocks; and (iii) a higher conversion
      rate of organic substrate to biomethane. Also a small amount of biohydrogen was
      detected from the first stage of the two-stage reactor making this system
      attractive for biohythane production. As the digestate contains ammoniacal
      nitrogen, re-circulating it provided the necessary alkalinity in the systems,
      thus preventing an eventual failure by volatile fatty acids (VFA) accumulation.
      However, re-circulation also resulted in an ammonium accumulation, yielding a
      lower biomethane production. Based on the batch experimental results the 50%
      inhibitory concentration of total ammoniacal nitrogen on the methanogenic
      activities was calculated as 3.8 g/L, corresponding to 146 mg/L free ammonia for
      the inoculum used for this research. The two-stage system was affected by the
      inhibition more than the one-stage system, as it requires less alkalinity and the
      physically separated methanogens are more sensitive to inhibitory factors, such
      as ammonium and propionic acid.

PMID- 25613218
TI  - A study of suicidal ideation in acute ischemic stroke patients.
AB  - BACKGROUND: Increasing evidences indicate that stroke confers a substantial risk
      for suicidal ideation. The aim of this study was to identify risk factors of
      suicidal ideation in acute ischemic stroke patients. METHOD: A total of 271
      consecutive patients with acute ischemic stroke were recruited in Huai-He
      hospital or the First People's Hospital, Kaifeng City, China. Demographic and
      clinical variables were collected and evaluated. Suicidal ideation was assessed
      using the Beck Scale for Suicide Ideation (BSI). Multivariate logistic regression
      was applied to determine the risk factors of suicidal ideation. RESULTS: Suicidal
      ideation was identified in 29 patients (10.7%). It was more frequent in patients
      who lived in rural region, with pre-/post-stroke depression or diabetes, had a
      higher NIHSS score, had no confidence in disease treatment, or had a poor coping
      style. Living in rural region (OR 2.59, 95% CI 1.02-6.58), the presence of pre
      stroke depression (OR 11.74, 95% CI 4.45-31.01), stroke severity (OR 1.20, 95% CI
      1.08-1.33), having no confidence in disease treatment (OR 14.70, 95% CI 2.60
      83.15), and post-stroke depression (OR 16.22, 95% CI 6.40-41.10) were independent
      risk factors of suicidal ideation. CONCLUSION: Several factors may be associated
      with an increased risk of suicidal ideation in acute ischemic stroke patients,
      including pre-/post-stroke depression, more severe stroke, having no confidence
      in treatment, as well as living in rural region. Our findings may have
      implication in risk assessment and intervention for acute ischemic stroke
      patients in reducing the burdens of suicidal ideation.

PMID- 25613219
TI  - Clinical Significance of First-Trimester Screening of the Retronasal Triangle for
      Identification of Primary Cleft Palate.
AB  - OBJECTIVE: To investigate the use of the retronasal triangle (RNT) for
      identification of orofacial cleft (OC) in the first trimester and the clinical
      application of three-dimensional (3D) ultrasound techniques for confirming the
      diagnosis of OC. METHODS: A total of 5,054 women with singleton pregnancies
      underwent first-trimester screening for Down syndrome at 11-13(+6) weeks. The RNT
      was scanned in each fetus, and 3D volumetric images of cases with abnormal or
      indeterminate RNT were obtained. RESULTS: Satisfactory images were obtained from
      all cases. Seven cases (1.40/00) of abnormal RNT were diagnosed as OC in the
      first trimester, which were confirmed at a 16 weeks scan or at a postmortem
      examination. One case that was considered a normal RNT was diagnosed with OC at
      22(+2) weeks and after term delivery. Six cases of indeterminate RNT were
      diagnosed as normal by 3D ultrasound. Identification of OC by visualization of
      the RNT in the first trimester had a sensitivity of 87.5% and a specificity of
      99.9%. CONCLUSION: The RNT is an important sonographic landmark that has a high
      sensitivity and specificity for the detection of OC in the first trimester. 3D
      ultrasound is an important tool that aids in confirming diagnosis of OC in the
      first and second trimesters.

PMID- 25613223
TI  - NMR resonance assignments of the lantibiotic immunity protein NisI from
      Lactococcus lactis.
AB  - The lantibiotic nisin is a small antimicrobial peptide which acts against a wide
      range of Gram-positive bacteria. Nisin-producing Lactococcus lactis strains
      express four genes for self-protection against their own antimicrobial compound.
      This immunity system consists of the lipoprotein NisI and the ABC transporter
      NisFEG. NisI is attached to the outside of the cytoplasmic membrane via a
      covalently linked diacylglycerol anchor. Both the lipoprotein and the ABC
      transporter are needed for full immunity but the exact immunity mechanism is
      still unclear. To gain insights into the highly specific immunity mechanism of
      nisin producing strains on a structural level we present here the backbone
      resonance assignment of NisI (25.8 kDa) as well as the virtually complete
      (1)H,(15)N,(13)C chemical shift assignments for the isolated 12.7 kDa N-terminal
      and 14.6 kDa C-terminal domains of NisI. 

PMID- 25613224
TI  - Modification of 3-arylisoquinolines into 3,4-diarylisoquinolines and assessment
      of their cytotoxicity and topoisomerase inhibition.
AB  - Inspired by the initial success of the monoarylisoquinolines and the quest to
      identify more potent and selective anticancer agents with topoisomerase (topo)
      inhibitory activity, series of diarylisoquinolines (3,4-diarylisoquinolones and
      3,4-diarylisoquinolinamines) were designed and synthesized. Synthesis of these
      compounds primarily involved lithiated toluamide-benzonitrile cycloaddition,
      Suzuki coupling, and nucleophilic aromatic substitution reactions. Eight of the
      derivatives were selectively toxic against human ductal breast epithelial tumor
      cells (T47D), human prostate cancer cells (DU145), and human colorectal
      adenocarcinoma cells (HCT-15), but had no effect on normal human breast
      epithelial cells (MCF10A). The topo inhibitory activities of the
      diarylisoquinoline compounds were relatively dependent upon their chemical
      structure. 3,4-Diarylisoquinolones generally did not inhibit topo I and only
      showed moderate inhibition of topo II. In contrast, several 3,4
      diarylisoquinolinamines showed superior topo I inhibitory activity.
      Isoquinolinamine derivatives had greater affinity for topo I than for topo II.
      Topo inhibition by 3,4-diarylisoquinolines was further supported by docking
      models showing intercalative and/or H-bond interactions between these compounds
      and the DNA/topo(s). An analysis of the correlation between the cytotoxicity and
      topo inhibition of these compounds indicated that the primary biological target
      of derivatives with potent cytotoxicity was topo, which in turn establishes
      diaryl-substituted isoquinolines as a novel class of potential anticancer drugs. 

PMID- 25613225
TI  - Integrated metagenomics and network analysis of soil microbial community of the
      forest timberline.
AB  - The forest timberline responds quickly and markedly to climate changes, rendering
      it a ready indicator. Climate warming has caused an upshift of the timberline
      worldwide. However, the impact on belowground ecosystem and biogeochemical cycles
      remain elusive. To understand soil microbial ecology of the timberline, we
      analyzed microbial communities via 16s rRNA Illumina sequencing, a microarray
      based tool named GeoChip 4.0 and a random matrix theory-based association network
      approach. We selected 24 sampling sites at two vegetation belts forming the
      timberline of Shennongjia Mountain in Hubei Province of China, a region with
      extraordinarily rich biodiversity. We found that temperature, among all of
      measured environmental parameters, showed the most significant and extensive
      linkages with microbial biomass, microbial diversity and composition at both
      taxonomic and functional gene levels, and microbial association network.
      Therefore, temperature was the best predictor for microbial community variations
      in the timberline. Furthermore, abundances of nitrogen cycle and phosphorus cycle
      genes were concomitant with NH4(+)-N, NO3(-)-N and total phosphorus, offering
      tangible clues to the underlying mechanisms of soil biogeochemical cycles. As the
      first glimpse at both taxonomic and functional compositions of soil microbial
      community of the timberline, our findings have major implications for predicting
      consequences of future timberline upshift. 

PMID- 25613226
TI  - Regulation of Th17/Treg function contributes to the attenuation of chronic airway
      inflammation by icariin in ovalbumin-induced murine asthma model.
AB  - Icariin which is a flavonoid glucoside isolated from Epimedium brevicornu Maxim,
      has been reported to have anti-osteoporotic, anti-inflammatory and anti
      depressant-like activities. In this study, we observed the effect of icariin on
      airway inflammation of ovalbumin (OVA)-induced murine asthma model and the
      associated regulatory mode on T-helper (Th)17 and regulatory T (Treg) cell
      function. Our data revealed that chronic OVA inhalation induced a dramatic
      increase in airway resistance (RL) and decrease in the lung dynamic compliance
      (Cdyn), and icariin and DEX treatment caused significant attenuation of such
      airway hyperresponsiveness (AHR). BALF cell counts demonstrated that icariin and
      DEX led to a prominent reduction in total leukocyte as well as lymphocyte,
      eosinophil, neutrophil, basophil and monocyte counts. Histological analysis
      results indicated that icariin and DEX alleviated the inflammatory cells
      infiltrating into the peribronchial tissues and goblet cells hyperplasia and
      mucus hyper-production. Flow cytometry test demonstrated that icariin or DEX
      administration resulted in a significant percentage reduction in CD4+RORgammat+ T
      cells and elevation of CD4+Foxp3+ T cells in BALF. Furthermore, icariin or DEX
      caused a significant reduction in IL-6, IL-17 and TGF-beta level in BALF.
      Unfortunately, icariin had no effect on IL-10 level in BALF. Western blot assay
      found that icariin or DEX suppressed RORgammat and promoted Foxp3 expression in
      the lung tissue. qPCR analysis revealed that icariin and DEX resulted in a
      notable decrease in RORgammat and increase in Foxp3 mRNA expression in isolated
      spleen CD4+ T cell. In conclusion, our results suggested that icariin was
      effective in the attenuation of AHR and chronic airway inflammatory changes in
      OVA-induced murine asthma model, and this effect was associated with regulation
      of Th17/Treg responses, which indicated that icariin may be used as a potential
      therapeutic method to treat asthma with Th17/Treg imbalance phenotype. 

PMID- 25613228
TI  - Dipyridamole-induced C-type natriuretic peptide mRNA overexpression in a minipig
      model of pacing-induced left ventricular dysfunction.
AB  - Dipyridamole (DP) restores ischemic tissue blood flow stimulating angiogenesis in
      eNOS-dependent pathways. C-type natriuretic peptide (CNP) is expected to mimic
      the migration-stimulatory effect of NO via a cGMP-dependent mechanism. Aim of
      this study was to assess the role of concomitant treatment with DP on CNP levels
      in blood and myocardial tissue of minipigs with left ventricular dysfunction
      (LVD) induced by pacing at 200bpm in the right ventricular apex. Minipigs with DP
      therapy (DP+, n=4) or placebo (DP-, n=4) and controls (C-SHAM, n=4) underwent 2D
      EchoDoppler examination and blood collection before and after 4 weeks of pacing,
      when cardiac tissue was collected. Histological/immunohistochemical analyses were
      performed. CNP levels were determined by radioimmunoassay; cardiac CNP, BNP,
      natriuretic receptors expression by Real-Time PCR. After pacing, cardiac
      parameters resulted less impaired in DP+ compared to DP-. Histological sections
      presented normal morphology while the arteriolar density resulted: C-SHAM: 9.0+/
      1.2; DP-: 4.9+/-0.3; DP+: 6.5+/-0.6number/mm(2); C-SHAM vs DP- and DP+ p=0.004,
      p=0.04, respectively. CNP mRNA resulted lower in DP- compared to C-SHAM and DP+
      as well as NPR-B (p=0.011, DP- vs DP+). Both NPR-A/NPR-C mRNA expressions were
      significantly (p<0.001) lower both in DP- and DP+ compared to C-SHAM. BNP mRNA
      was higher in LVD. CNP plasma levels showed a similar trend with respect to gene
      expression (C-SHAM: 30.5+/-15; DP-: 18.6+/-5.5; DP+: 21.2+/-4.7pg/ml). These data
      suggest that DP may serve as a preconditioning agent to increase the protective
      CNP-mediated endocrine response in LVD. This response, mediated by its specific
      receptor NPR-B, may offer new insights into molecular targets for treatment of
      LVD. 

PMID- 25613229
TI  - Artificially maturated [FeFe] hydrogenase from Chlamydomonas reinhardtii: a
      HYSCORE and ENDOR study of a non-natural H-cluster.
AB  - Hydrogenases are enzymes that catalyze the oxidation of H2 as well as the
      reduction of protons to form H2. The active site of [FeFe] hydrogenase is
      referred to as the "H-cluster" and consists of a "classical" [4Fe-4S] cluster
      connected via a bridging cysteine thiol group to a unique [2Fe]H sub-cluster,
      containing CN(-) and CO ligands as well as a bidentate azadithiolate ligand. It
      has been recently shown that the biomimetic [Fe2(adt)(CO)4(CN)2](2-) (adt(2-) =
      azadithiolate) complex resembling the diiron sub-cluster can be inserted in vitro
      into the apo-protein of [FeFe] hydrogenase, which contains only the [4Fe-4S] part
      of the H-cluster, resulting in a fully active enzyme. This synthetic tool allows
      convenient incorporation of a variety of diiron mimics, thus generating
      hydrogenases with artificial active sites. [FeFe] hydrogenase from Chlamydomonas
      reinhardtii maturated with the biomimetic complex [Fe2(pdt)(CO)4(CN)2](2-) (pdt(2
      ) = propanedithiolate), in which the bridging adt(2-) ligand is replaced by pdt(2
      ), can be stabilized in a state strongly resembling the active oxidized (Hox)
      state of the native protein. This state is EPR active and the signal originates
      from the mixed valence Fe(I)Fe(II) state of the diiron sub-cluster. Taking
      advantage of the variant with (15)N and (13)C isotope labeled CN(-) ligands we
      performed HYSCORE and ENDOR studies on this hybrid protein. The (13)C hyperfine
      couplings originating from both CN(-) ligands were determined and assigned. Only
      the (15)N coupling from the CN(-) ligand bound to the terminal iron was observed.
      Detailed orientation selective ENDOR and HYSCORE experiments at multiple field
      positions enabled the extraction of accurate data for the relative orientations
      of the nitrogen and carbon hyperfine tensors. These data are consistent with the
      crystal structure assuming a g-tensor orientation following the local symmetry of
      the binuclear sub-cluster. 

PMID- 25613227
TI  - Using theories of sexual selection and sexual conflict to improve our
      understanding of plant ecology and evolution.
AB  - Today it is accepted that the theories of sexual selection and sexual conflict
      are general and can be applied to both animals and plants. However, potentially
      due to a controversial history, plant studies investigating sexual selection and
      sexual conflict are relatively rare. Moreover, these theories and concepts are
      seldom implemented in research fields investigating related aspects of plant
      ecology and evolution. Even though these theories are complex, and can be
      difficult to study, we suggest that several fields in plant biology would benefit
      from incorporating and testing the impact of selection pressures generated by
      sexual selection and sexual conflict. Here we give examples of three fields where
      we believe such incorporation would be particularly fruitful, including (i)
      mechanisms of pollen-pistil interactions, (ii) mating-system evolution in
      hermaphrodites and (iii) plant immune responses to pests and pathogens. 

PMID- 25613230
TI  - The new reagent therefore reveals roles for CD4+LAP+ T cells in
      immunosuppression, inflammation and autoimmunity.

PMID- 25613235
TI  - Between-session and within-session habituation in Prolonged Exposure Therapy for
      posttraumatic stress disorder: a hierarchical linear modeling approach.
AB  - Prolonged Exposure Therapy is a frontline intervention for posttraumatic stress
      disorder, but the mechanisms underlying its efficacy are not fully understood.
      Previous research demonstrates that between- and within-session habituation of
      fear during exposure is associated with treatment outcome, but these calculations
      are historically performed with summary statistics such as mean subjective units
      of distress (SUDS). This question could be better assessed with an analytic
      technique that uses all SUDS measurements available within sessions. Hierarchical
      linear modeling was used to investigate the impact of treatment response on SUDS
      nested within therapy sessions nested within 14 patients. Symptom change (t=
      2.43, p=.03) and responder status (t=-2.68, p=.02) predicted slope of SUDS across
      sessions, but did not reliably predict slope of SUDS within-session, indicating
      that high responders demonstrated differential between- but not within-session
      habituation. Thus, individuals who show greater habituation between treatment
      sessions may be more likely to respond to treatment. 

PMID- 25613236
TI  - Pseudoamniotic Band Syndrome after In Utero Intervention for Twin-to-Twin
      Transfusion Syndrome: Case Reports and Literature Review.
AB  - Pseudoamniotic band syndrome (PABS) is a rare iatrogenic complication that arises
      after invasive procedures in monochorionic twins. We report 3 cases of PABS, 2
      after fetoscopic laser photocoagulation and 1 after bipolar cord coagulation. Two
      cases were detected antenatally by ultrasound; out of the two, one underwent
      successful fetoscopic release of amniotic band, which is the first report in twin
      pregnancy to our knowledge. In our centre, the incidence of PABS was found to be
      2%. There were 25 cases of PABS reported previously, of which 12 cases with
      clinical details were reviewed together with our 3 cases. The fetal limbs were
      involved in all 15 cases, leading to constriction or amputation. The umbilical
      cord was involved in 2 cases, resulting in fetal death in one and pregnancy
      termination in the other. Antenatal detection of PABS is rare (27%; 4/15) as this
      requires a high index of suspicion. Serial postoperative targeted ultrasound
      surveillance of the fetal limbs and umbilical cord is necessary, particularly
      when features of septostomy or chorioamniotic membrane separation are found.
      Colour Doppler examination for the perfusion of the affected limb should be
      performed when PABS is detected. Fetoscopic release of amniotic band could
      salvage the fetal limb from amputation when impaired blood flow is detected. 

PMID- 25613234
TI  - Recent Advances on Small-Molecule Survivin Inhibitors
AB  - Survivin, a member of the inhibitor of apoptosisproteins family, is highly
      expressed in most human neoplasms, but its expression is very low or undetectable
      in terminally differentiated normal tissues. Survivin has been shown to inhibit
      cancer cell apoptosis and promote cell proliferation. The overexpression of
      survivin closely correlates with tumor progression and drug resistance. Because
      of its key role in tumor formation and maintenance, survivin is considered as an
      ideal target for anticancer treatment. However, the development of small-molecule
      survivin inhibitors has been challenging due to the requirement to disrupt the
      protein-protein interactions. Currently only a limited number of survivin
      inhibitors have been developed in recent years, and most of these inhibitors
      reduce survivin levels by interacting with other biomolecules instead of directly
      interacting with survivin protein. Despite these challenges, developing potent
      and selective small-molecule survivin inhibitors will be important in both basic
      science to better understand survivin biology and in translational research to
      develop potentially more effective, broad-spectrum anticancer agents. In this
      review, the functions of survivin and its role in cancer are summarized. Recent
      developments, challenges, and future direction of small-molecule survivin
      inhibitors are also discussed in detail.

PMID- 25613237
TI  - Impact of anaemia on mortality and its causes in elderly patients with acute
      coronary syndromes.
AB  - BACKGROUND: Prognostic impact of anaemia in the elderly with acute coronary
      syndromes has not been specifically analysed, and little information exists about
      causes of mortality in this setting. METHODS: We prospectively included
      consecutive patients with acute coronary syndromes. Anaemia was defined as
      haemoglobin < 130 g/L in men, and < 120 g/L in women. Primary outcome was mid
      term mortality and its causes. Analyses were performed by Cox regression method.
      RESULTS: We included 2128 patients, of whom 394 (18.6%) were aged 75 years or
      older. Anaemia was more common in the elderly (40.4% vs 19.5%, p <0.001). Mean
      follow-up was 386 days. Anaemia independently predicted overall mortality (HR
      1.47, 95% CI 1.05-2.06), cardiac mortality (HR 1.76, 95% CI 1.06-2.94) and non
      cardiac mortality (HR 1.59, 95% CI 1.03-2.45) in the overall cohort. In young
      patients the association between anaemia and mortality was significant only for
      non-cardiac causes. The association between anaemia and mortality was not
      significant in the elderly (HR 1.08, 95% CI 0.71-1.63, p 0.736). CONCLUSIONS: The
      impact of anaemia on cause specific of mortality seem to be different according
      to age subgroup. The association between anaemia and mortality was not observed
      in elderly patients from our series.

PMID- 25613238
TI  - Who gets stroke prevention? Stroke prevention in atrial fibrillation patients in
      the inpatient setting.
AB  - BACKGROUND: Current guidelines strongly recommend antithrombotic therapy,
      particularly warfarin, for stroke prevention in atrial fibrillation (AF) patients
      at high risk of stroke. Despite this, use of these medications is far from
      optimal. The aim of this study was to describe the use of stroke prevention
      medication in inpatients and identify factors associated with prescription in one
      local health district in Sydney, Australia. METHODS: A prospective audit of
      medical records for patients admitted with an AF diagnosis to five hospitals in
      the health district and excluding cardiac surgery patients was undertaken.
      Patients were classified as high or low for stroke risk as well as for risk of
      bleeding and predictors were identified by logistic regression. RESULTS: A total
      of 204 patients were enrolled from July 2012 to April 2013, with a mean age of 75
      years (SD 13) and half (50%) were male. Valve disease was present in 17% and 15%
      received a procedure for their AF (cardioversion/ablation/pulmonary vein
      isolation). Patients were least likely to be prescribed warfarin/novel oral
      anticoagulant (NOAC) if they were non-valvular and did not undergo
      cardioversion/ablation (p=.03), and least likely to be prescribed aspirin if they
      had no AF procedure (p=.01). In non-valvular patients who did not have
      cardioversion/ablation the odds of being prescribed warfarin/NOAC were increased
      by being classified at high risk of stroke (OR 3.1, 95% CI 1.0 -9.5) and
      decreased if there was a prescription for aspirin (OR .3. 95% CI .1 -.6).
      CONCLUSIONS: Overall use of stroke prevention medication indicates that gaps
      remain in translation of evidence into clinical practice.

PMID- 25613239
TI  - Case report: radial artery occlusion post-radial angiogram in essential
      thrombocytosis.
AB  - Coronary angiographies that are performed via the radial artery generally have
      lower bleeding complications, however, patients are at risk of radial artery
      occlusion, with resultant digital ischaemia. This report describes a case of
      digital ischaemia after transradial coronary angiography in a patient with
      essential thrombocytosis. Risk factors for thrombo-occlusive complications, and
      potential prevention strategies are also explored. 

PMID- 25613240
TI  - Rosuvastatin attenuates atrial structural remodelling in rats with myocardial
      infarction through the inhibition of the p38 MAPK signalling pathway.
AB  - OBJECTIVE: The purpose of this study was to verify the hypothesis that
      rosuvastatin attenuates atrial structural remodelling in rats with myocardial
      infarction (MI) through the regulation of the p38 mitogen-activated protein
      kinase (MAPK) signalling pathway. METHODS: A total of 66 rats were used in this
      study to establish a model of MI. The 56 rats that survived the first 24h after
      surgery were randomly divided into four groups: the control group (C group), the
      rosuvastatin group (R group), the low-dose torasemide group (T1 group), and the
      high-dose torasemide group (T2 group). The four groups of rats received daily
      intragastric administration of normal saline, rosuvastatin, or torasemide (T1:
      1mg/kg body weight; T2: 2mg/kg body weight) for a total of four weeks. The rats
      in the sham-operated group (n=14) also received daily intragastric administration
      of normal saline for four weeks. After four weeks of intervention, the left
      ventricular end-diastolic pressure (LVEDP) was measured in all groups of rats by
      haemodynamic methods. The rats were then sacrificed, and the left atrial tissues
      were collected. The collagen volume fractions (CVFs) in the left atrial tissues
      were determined using Masson's trichrome staining. The expression of
      phosphorylated p38 (P-p38) MAPK in the left atrial tissues was examined by
      immunohistochemistry and western blot analysis. RESULTS: The results showed that
      LVEDP, CVF, and P-p38 MAPK expression were drastically elevated in the four MI
      groups in comparison to the sham-operated group (p<0.001). Rosuvastatin elevated
      the left ventricular fractional shortening (LVFS) and left ventricular ejection
      fraction (LVEF). Both rosuvastatin and torasemide improved the haemodynamic
      parameters. No significant difference was detected in LVEDP between the R group
      and the T1 group (p=0.37). In contrast, LVEDP was significantly higher in the R
      group than in the T2 group (p <0.05). CVF (%) was markedly decreased in the R
      group compared to the C, T1, and T2 groups (decreased by 47.4%, 28%, and 20.1%,
      respectively). Immunohistochemical analysis showed that the indices of P-p38 MAPK
      positive cells were significantly decreased in the R group in comparison with the
      C, T1, and T2 groups (decreased by 44.6%, 36.6%, and 21.4%, respectively).
      Western blot analysis demonstrated that P-p38 MAPK expression was markedly
      reduced in the R group compared with the C and T1 groups (reduced by 67% and
      40.5%, respectively). The level of P-p38 MAPK in the R group was slightly higher
      than in the T2 group. However, the difference was not statistically significant
      (p>0.05). CONCLUSION: Rosuvastatin attenuates atrial structural remodelling in
      rats with MI. The mechanism underlying this phenomenon may be associated with the
      downregulation of P-p38 MAPK by rosuvastatin.

PMID- 25613241
TI  - Platelet-derived growth factor-B (PDGF-B) induced by hypoxia promotes the
      survival of pulmonary arterial endothelial cells through the PI3K/Akt/Stat3
      pathway.
AB  - BACKGROUND/AIMS: Pulmonary arterial endothelial plexiform lesions are a basic
      pathological change associated with pulmonary vascular remodeling and are
      characterized by the formation of tumorlets as a result of over-growth of
      endothelial cells. Accumulating evidence suggests that platelet-derived growth
      factor (PDGF) participates in regulating the progression of pulmonary arterial
      hypertension. However, whether PDGF promotes the survival of pulmonary arterial
      endothelial cells (PAECs), as well as the specific molecular mechanisms that
      underlie its actions, remains unknown. METHODS: MTT assays, caspase-3 and caspase
      9 activity assays and western blot analysis were performed. RESULTS: We found
      that both the mRNA and protein expression of PDGF-B was induced by hypoxia and
      that the inhibitory effects exerted by hypoxia on apoptosis were attenuated by
      inhibitors of PDGF beta. Moreover, PDGF-B inhibited apoptosis in a dose-dependent
      manner by stimulating the phosphorylation of both Akt and Stat3, and the PI3K/AKT
      pathway serves as an up-stream participant in the Stat3 activation stimulated by
      PDGF-B. Additionally, the anti-apoptotic effects of PDGF-B were abolished when
      PAECs were treated with either an inhibitor or small interfering RNA targeting
      Stat3. CONCLUSIONS: These observations suggest that PDGF-B is induced by hypoxia
      and protects against apoptosis via the PI3K/Akt/Stat3 signaling pathway.

PMID- 25613242
TI  - What happens next?

PMID- 25613243
TI  - Guidelines: Sound principles.

PMID- 25613244
TI  - Foreign objects: Rubber damn!

PMID- 25613245
TI  - Guidelines: Inform and clarify.

PMID- 25613246
TI  - Prosthodontics: Enigmatic dental appliance.

PMID- 25613247
TI  - Infection control: Oral-systemic relationships.

PMID- 25613248
TI  - Dental patients: Transgender issues.

PMID- 25613251
TI  - ARF hike: GDC defeated but ARF hike stands.

PMID- 25613256
TI  - A dentist's life: Making the hard work worth it.

PMID- 25613257
TI  - Children's food heroes and zeroes of 2014.

PMID- 25613258
TI  - Nigel Hunt: 'I wanted to be an orthodontist before I wanted to be a dentist'.
AB  - Professor Nigel Hunt has been Professor and Head of the Department of
      Orthodontics at the UCL Eastman Dental Institute since 1998. His clinical
      interest is the management of craniofacial deformity, and he leads a research
      team in the field of craniofacial reconstruction and tissue engineering. Nigel
      was elected Dean of the Faculty of Dental Surgery at the Royal College of
      Surgeons of England in June 2014. He is also the immediate past-Chairman of the
      British Orthodontic Society and its President for 2015. 

PMID- 25613259
TI  - Restoration of the root canal treated tooth.
AB  - When considering endodontically treated teeth, the quality of the restoration is
      important from the outset. It sheds light into possible causes of pulp necrosis
      or failure of endodontic treatment and influences the outcome of future
      endodontic treatment. A tooth undergoing endodontic treatment requires an
      effective coronal seal during and following completion of endodontic treatment.
      This paper discusses, using the available literature, the maintenance of optimal
      coronal seal and coronal integrity during and after root canal treatment. 

PMID- 25613260
TI  - A review of dental treatment of head and neck cancer patients, before, during and
      after radiotherapy: part 1.
AB  - The incidence of head and neck cancer is on the rise. Most head and neck cancers
      are treated with surgery, radiotherapy, chemotherapy or a combination of these
      modalities. Patients undergoing radiotherapy can experience several unwanted oral
      side effects, which have both short and long term implications. Dental general
      practitioners should be aware of these implications and should liaise closely
      with the restorative consultants and the oncology team to establish the best oral
      care pathway. This two-part series is a review of the oral changes that occur
      during and after radiotherapy and the oral management of head and neck oncology
      before, during and after radiotherapy. This article deals with both immediate
      sequelae such as cellulitis, mucositis, dysphagia, dysguesia and weight loss as
      well as long term sequelae such as rampant caries, trismus, xerostomia and
      osteoradionecrosis. It also encompasses the importance and need for pre
      radiotherapy assessment.

PMID- 25613266
TI  - Summary of: Operator's ability at assessing a high-speed (air turbine) handpiece
      before use: an audit.

PMID- 25613261
TI  - A review of dental treatment of head and neck cancer patients, before, during and
      after radiotherapy: part 2.
AB  - The incidence of head and neck cancer is on the rise. Radiation therapy is one of
      the major treatment modalities for the management of oral malignancies. As with
      any treatment modality, radiation therapy is associated with various
      complications. The second part of this series is a review of the oral changes
      that occur during and after radiotherapy and the oral management of head and neck
      oncology patients before, during and after radiotherapy. Dental practitioners
      will encounter patients who have been affected by cancer or who are current
      cancer patents. General dental practitioners (GDPs) have a vital and proactive
      role in supporting such patients. The aim of this article is to review the oral
      management of these patients during and after radiotherapy, and gives practical
      advice for GDPs and their teams in the long-term care of these patients. 

PMID- 25613267
TI  - The views of part-time clinical teachers regarding their role in undergraduate
      education at the University of Bristol Dental School.
AB  - INTRODUCTION: UK dental schools are reliant on part-time teachers to deliver the
      clinical educational component of the course, the majority with a background in
      general dental practice. Opportunities for promotion are limited, as is the
      support for obtaining educational qualifications. The aim of this study was to
      ascertain the views of such teachers at a dental school. MATERIALS AND METHODS:
      An anonymous online survey was used to obtain both qualitative and quantitative
      views. RESULTS: The response rate was 80%. The school has n = 50 part-time
      clinical teachers, who have been teaching for, on average ten years, and for
      three sessions per week. Eighteen percent of teachers are recognised specialists.
      Forty-six percent of respondents have a formal teaching qualification, mostly at
      certificate level, and 55% thought it necessary to acquire a formal teaching
      qualification. Eighty-eight percent were happy with their role as clinical
      teachers. CONCLUSION: This study demonstrates that despite the lack of support
      and prospect of career progression, the majority of part-time clinical teachers
      at this institution are satisfied with their role.

PMID- 25613281
TI  - Operator's ability at assessing a high-speed (air turbine) handpiece before use:
      an audit.
AB  - BACKGROUND: The 'high-speed' (air turbine) handpiece is used extensively across
      many dental disciplines and the ability of clinicians to detect faulty handpieces
      is essential. AIM: The primary aim of this audit was to determine the proportion
      of participants who could correctly identify unsafe handpieces. Secondary aims
      were to determine the proportion that had previous training on the topic and
      determine whether an educational video could improve scores. METHOD: Eighty
      participants completed the first round of audit. They were asked to inspect seven
      handpieces, five of which were faulty, with three being classed as unsafe. After
      the intervention (educational sessions and distribution of a video) a second
      round of audit was completed on 69 participants. RESULTS: The ability to detect
      the three unsafe handpieces increased from 10% to 44% over the two rounds of
      audit. In the second round the highest score obtained was by those who had
      received the intervention, 77%. The lowest score, 14%, was by those who had not
      received the intervention. Nine percent of participants in the first round stated
      they had previously had training on handpiece inspection and none of these
      participants identified the three unsafe handpieces. CONCLUSION: This audit has
      highlighted that there is a knowledge deficiency with regards to air turbine
      handpiece safety and inspection. We have shown that introduction of a simple
      education video can have an impact on dentists and students abilities to detect
      unsafe faults. We have already introduced this into the undergraduate curriculum
      in our school and we aim to also raise awareness within the dental community.

PMID- 25613282
TI  - The impact of social and family-related factors on women's stress experience in
      household and family work.
AB  - OBJECTIVES: This study explores the contribution of social and family-related
      factors to women's experience of an effort-reward imbalance (ERI) in household
      and family work. METHODS: Using a population-based sample of German mothers (n =
      3,129), we performed stepwise logistic regression analysis in order to determine
      the relative impact of social and family-related factors on ERI. RESULTS: All
      factors investigated showed a significant association with at least one ERI
      component. Considering all predictors simultaneously in the multivariate analysis
      resulted in a decrease in significance of socioeconomic status in explaining the
      effort-reward ratio while the impact on low reward partly remained significant.
      In addition, age of youngest child, number of children, lower levels of perceived
      social support, domestic work inequity and negative work-to-family spillover,
      irrespective of being half- or full-time employed, revealed to be important in
      predicting ERI. CONCLUSIONS: The experience of ERI in domestic work is influenced
      by the social and family environment. Particularly among socially disadvantaged
      mothers, lack of social recognition for household and family work proved to be a
      relevant source of psychosocial stress.

PMID- 25613283
TI  - Super-resolution reconstruction of diffusion parameters from diffusion-weighted
      images with different slice orientations.
AB  - PURPOSE: Diffusion MRI is hampered by long acquisition times, low spatial
      resolution, and a low signal-to-noise ratio. Recently, methods have been proposed
      to improve the trade-off between spatial resolution, signal-to-noise ratio, and
      acquisition time of diffusion-weighted images via super-resolution reconstruction
      (SRR) techniques. However, during the reconstruction, these SRR methods neglect
      the q-space relation between the different diffusion-weighted images. METHOD: An
      SRR method that includes a diffusion model and directly reconstructs high
      resolution diffusion parameters from a set of low resolution diffusion-weighted
      images was proposed. Our method allows an arbitrary combination of diffusion
      gradient directions and slice orientations for the low resolution diffusion
      weighted images, optimally samples the q- and k-space, and performs motion
      correction with b-matrix rotation. RESULTS: Experiments with synthetic data and
      in vivo human brain data show an increase of spatial resolution of the diffusion
      parameters, while preserving a high signal-to-noise ratio and low scan time.
      Moreover, the proposed SRR method outperforms the previous methods in terms of
      the root-mean-square error. CONCLUSION: The proposed SRR method substantially
      increases the spatial resolution of MRI that can be obtained in a clinically
      feasible scan time.

PMID- 25613284
TI  - Genome-wide immunity studies in the rabbit: transcriptome variations in
      peripheral blood mononuclear cells after in vitro stimulation by LPS or PMA
      Ionomycin.
AB  - BACKGROUND: Our purpose was to obtain genome-wide expression data for the rabbit
      species on the responses of peripheral blood mononuclear cells (PBMCs) after in
      vitro stimulation by lipopolysaccharide (LPS) or phorbol myristate acetate (PMA)
      and ionomycin. This transcriptome profiling was carried out using microarrays
      enriched with immunity-related genes, and annotated with the most recent data
      available for the rabbit genome. RESULTS: The LPS affected 15 to 20 times fewer
      genes than PMA-Ionomycin after both 4 hours (T4) and 24 hours (T24), of in vitro
      stimulation, in comparison with mock-stimulated PBMCs. LPS induced an
      inflammatory response as shown by a significant up-regulation of IL12A and CXCL11
      at T4, followed by an increased transcription of IL6, IL1B, IL1A, IL36, IL37,
      TNF, and CCL4 at T24. Surprisingly, we could not find an up-regulation of IL8
      either at T4 or at T24, and detected a down-regulation of DEFB1 and BPI at T24. A
      concerted up-regulation of SAA1, S100A12 and F3 was found upon stimulation by
      LPS. PMA-Ionomycin induced a very early expression of Th1, Th2, Treg, and Th17
      responses by PBMCs at T4. The Th1 response increased at T24 as shown by the
      increase of the transcription of IFNG and by contrast to other cytokines which
      significantly decreased from T4 to T24 (IL2, IL4, IL10, IL13, IL17A, CD69) by
      comparison to mock-stimulation. The granulocyte-macrophage colony-stimulating
      factor (CSF2) was by far the most over-expressed gene at both T4 and T24 by
      comparison to mock-stimulated cells, confirming a major impact of PMA-Ionomycin
      on cell growth and proliferation. A significant down-regulation of IL16 was
      observed at T4 and T24, in agreement with a role of IL16 in PBMC apoptosis.
      CONCLUSIONS: We report new data on the responses of PBMCs to LPS and PMA
      Ionomycin in the rabbit species, thus enlarging the set of mammalian species for
      which such reports exist. The availability of the rabbit genome assembly together
      with high throughput genomic tools should pave the way for more intense genomic
      studies for this species, which is known to be a very relevant biomedical model
      in immunology and physiology.

PMID- 25613285
TI  - Identification of novel genes responsible for salt tolerance by transposon
      mutagenesis in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae strains tolerant to salt stress are important for the
      production of single-cell protein using kimchi waste brine. In this study, two
      strains (TN-1 and TN-2) tolerant of up to 10 % (w/v) NaCl were isolated by
      screening a transposon-mediated mutant library. The determination of transposon
      insertion sites and Northern blot analysis identified two genes, MDJ1 and VPS74,
      and revealed disruptions of the open reading frame of both genes, indicating that
      salt tolerance can be conferred. Such tolerant phenotypes reverted to sensitive
      phenotypes on the autologous or overexpression of each gene. The two transposon
      mutants grew faster than the control strain when cultured at 30  degrees C in
      rich medium containing 5, 7.5 or 10 % NaCl. The genes identified in this study
      may provide a basis for application in developing industrial yeast strains. 

PMID- 25613286
TI  - Methods and advances in metabolic flux analysis: a mini-review.
AB  - Metabolic flux analysis (MFA) is one of the pillars of metabolic engineering.
      Over the past three decades, it has been widely used to quantify intracellular
      metabolic fluxes in both native (wild type) and engineered biological systems.
      Through MFA, changes in metabolic pathway fluxes are quantified that result from
      genetic and/or environmental interventions. This information, in turn, provides
      insights into the regulation of metabolic pathways and may suggest new targets
      for further metabolic engineering of the strains. In this mini-review, we discuss
      and classify the various methods of MFA that have been developed, which include
      stoichiometric MFA, (13)C metabolic flux analysis, isotopic non-stationary (13)C
      metabolic flux analysis, dynamic metabolic flux analysis, and (13)C dynamic
      metabolic flux analysis. For each method, we discuss key advantages and
      limitations and conclude by highlighting important recent advances in flux
      analysis approaches. 

PMID- 25613288
TI  - Editorial commentary: Antibiotic self-treatment of travelers' diarrhea: helpful
      or harmful?

PMID- 25613289
TI  - Ultrasound-Targeted Microbubble Destruction Enhances Gene Expression of microRNA
      21 in Swine Heart via Intracoronary Delivery.
AB  - BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) has proved to be a
      promising method for gene delivery. However, the feasibility and efficacy of UTMD
      mediated gene delivery to the heart of large animals remain unclear. The present
      study was to explore the probability of increasing the transfection of microRNA
      21 (miR-21) in swine heart by UTMD, and to search for the most suitable
      transfection conditions. METHODS: We first optimized ultrasound intensity for
      successful miR-21 delivery. After intravenous injection of miR-21/microbubble
      mixture (miR-21/MB), transthoracic ultrasound irradiation (US) was applied from
      the left anterior chest using different intensities (1, 2, and 3 W/cm(2)). Then
      the efficacy of UTMD-mediated miR-21 delivery into myocardium via intracoronary
      injection was explored. Solution of miR-21/MB was infused intravenously or
      intracoronarily with US over the heart. Swine undergoing phosphate-buffered
      saline (PBS) injection, miR-21/MB injection via ear vein or coronary artery
      without US served as the control. The dynamic changes of left ventricular
      ejection fraction (LVEF) and serum troponin I (cTnI) after UTMD were detected,
      then the left ventricular myocardium was harvested for hematoxylin and eosin
      (H&E) staining 4 days later; the expression levels of miR-21 and programmed cell
      death 4 (PDCD4) were detected by quantitative real time polymerase chain reaction
      (qRT-PCR) and Western blot, respectively. RESULTS: Results showed that pulse
      ultrasound at an intensity of 2 W/cm(2) and a 50% duty ratio for 20 minutes,
      there was no increase in serum cTnI, no histological sign of myocardial damage,
      and no noted cardiac dysfunction with relatively higher miR-21 expression (P <
      0.05). Compared to miR-21/MB alone, UTMD significantly increased gene expression
      in myocardium regardless of the delivery routes (P < 0.05). Interestingly, the
      transfection efficiency was found to be a little bit higher with intracoronary
      injection than that with intravenous injection, though the dose for intracoronary
      injection was half of the intravenous injection (P < 0.05). CONCLUSION: Under
      suitable conditions, UTMD can efficiently enhance gene expression in swine heart
      regardless of the delivery routes. The intravenous injection might be superior to
      intracoronary injection with less invasiveness and lower requirement of the
      technique. And for those undergoing percutaneous coronary intervention,
      intracoronary injection seems to be another alternative.

PMID- 25613287
TI  - Antimicrobials increase travelers' risk of colonization by extended-spectrum
      betalactamase-producing Enterobacteriaceae.
AB  - BACKGROUND: More than 300 million travelers visit regions with poor hygiene
      annually. A significant percentage of them become colonized by resistant
      intestinal bacteria such as extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-PE) and may transmit the strains to others and to
      medical care settings when they return home. Despite the threats to global
      healthcare caused by an upsurge in antimicrobial resistance, no effort has been
      centered on prevention of colonization while traveling. METHODS: Stool samples
      were collected from 430 Finns before and after traveling outside Scandinavia. All
      specimens were analyzed for ESBL- and carbapenemase-producing Enterobacteriaceae
      (CPE). Questionnaires were used to survey volunteers about use of antimicrobials
      as well as other potential risk factors. The results were subjected to
      multivariable analysis. RESULTS: Twenty-one percent (90/430) of the travelers
      became colonized by ESBL-PE and none by CPE. Geographic region, occurrence of
      travelers' diarrhea (TD), age, and use of antimicrobial (AB) for TD were
      identified as independent risk factors predisposing to contracting ESBL-PE.
      Eleven percent of those in subgroup TD-AB-, 21% in TD+AB-, and 37% in TD+AB+
      acquired ESBL-PE. The risk proved to be highest in South Asia (46%); 23% became
      colonized in subgroup TD-AB-, 47% in TD+AB-, and 80% in TD+AB+. In Southeast
      Asia, the rates were 14%, 37%, and 69%, respectively. CONCLUSIONS: TD and
      antimicrobials for TD proved to be independent risk factors, with up to 80% of
      TD+AB+ travelers contracting ESBL-PE. In modern pre-travel counseling for those
      visiting high-risk regions, travelers should be advised against taking
      antibiotics for mild or moderate TD.

PMID- 25613290
TI  - Multivesicular bodies differentiate exclusively in nutritive fast-dividing cells
      in Marcetia taxifolia galls.
AB  - Marcetia taxifolia (A. St.-Hil.) DC. hosts two gall morphotypes, a pistil-shaped
      gall induced by a Cecidomyiidae (Diptera) and a fusiform stem gall induced by a
      Lepidoptera. The cytological study of these galls aimed to answer how the
      difference in nutritive tissues of Diptera and Lepidoptera galls could be
      explained on cytological basis. The nutritive tissues of lepidopteran galls have
      a fast-dividing cell zone, the storage nutritive tissue, which replaces the cells
      of the typical nutritive tissue, where the larvae feed. The differentiation of
      multivesicular bodies in the plasma membrane occurred exclusively in these fast
      dividing cells of the lepidopteran galls, evidencing the meristematic condition
      of such tissue. The accumulation of reactive oxygen species (ROS) analyzed in
      situ in the nutritive cells is not sufficient to induce programmed cell death
      (PCD), as the cells of M. taxifolia have plastoglobules and accumulate
      polyphenols and terpenoids, which are diagnostic defenses against oxidative
      stress. The two taxa of galling insects have different nutritional requirements,
      thus inducing specific cytoplasm-enriched cells on their nutritive tissues. 

PMID- 25613291
TI  - Oxidative stress and autophagy: crucial modulators of kidney injury.
AB  - Both acute kidney injury (AKI) and chronic kidney disease (CKD) that lead to
      diminished kidney function are interdependent risk factors for increased
      mortality. If untreated over time, end stage renal disease (ESRD) is an
      inevitable outcome. Acute and chronic kidney diseases occur partly due to
      imbalance between the molecular mechanisms that govern oxidative stress,
      inflammation, autophagy and cell death. Oxidative stress refers to the cumulative
      effects of highly reactive oxidizing molecules that cause cellular damage.
      Autophagy removes damaged organelles, protein aggregates and pathogens by
      recruiting these substrates into double membrane vesicles called autophagosomes
      which subsequently fuse with lysosomes. Mounting evidence suggests that both
      oxidative stress and autophagy are significantly involved in kidney health and
      disease. However, very little is known about the signaling processes that link
      them. This review is focused on understanding the role of oxidative stress and
      autophagy in kidney diseases. In this review, we also discuss the potential
      relationships between oxidative stress and autophagy that may enable the
      development of better therapeutic intervention to halt the progression of kidney
      disease and promote its repair and resolution. 

PMID- 25613292
TI  - Flexor tendon repairs in children: Outcomes from a specialist tertiary centre.
AB  - We evaluate the functional outcomes of early active mobilization (EAM) after
      paediatric flexor tendon repair at one centre from 2006 to 2013. A generic
      rehabilitation protocol was used for the first four to six weeks: boxing glove
      immobilization (<5 years), dorsal blocking splint and cage (5-10 years) or dorsal
      blocking splint +/- cage (10-16 years). Outcomes were assessed using the Total
      Active Mobilization (TAM) method of the American Society for Surgery of the Hand
      and original Strickland criteria (OSC). Sixty-three fingers and 99 tendons were
      identified, in 57 children. Thirty-five per cent (n = 20) were in zone 2, 23% in
      zone 1, 18% in zone 5, 14% in zone 3 and 2% in zone 4. Good/excellent results
      were obtained in 82% by the TAM method and 79% by the OSC of those suitable for
      analysis (56 tendons in 44 children). The surgical approaches used varied in
      technique and material; a modified Kessler stitch (n = 42) using prolene (n = 60)
      represented the majority of core sutures. Epitendinous repair was employed in 76%
      of repairs (n = 75). The median length of hand therapy follow-up was 83.5 days
      (IQR 43.5-143.75 days). Complications included: one rupture, one post-operative
      infection requiring washout and three contractures, two requiring re-operation.
      EAM is a practical and safe way to rehabilitate children after flexor tendon
      repair, without increasing ruptures or adhesions. Most children under five are
      managed effectively in a bulky bandage. 

PMID- 25613294
TI  - Erratum to: Specific stressors in endonasal skull base surgery with and without
      navigation.

PMID- 25613293
TI  - Diminished serum repetin levels in patients with schizophrenia and bipolar
      disorder.
AB  - Repetin (RPTN) protein is a member of S100 family and is known to be expressed in
      the normal epidermis. Here we show that RPTN is ubiquitously expressed in both
      mouse and human brain, with relatively high levels in choroid plexus, hippocampus
      and prefrontal cortex. To investigate the expression of RPTN in neuropsychiatric
      disorders, we determined serum levels of RPTN in patients with schizophrenia (n =
      88) or bipolar disorder (n = 34) and in chronic psychostimulant users (n = 91).
      We also studied its expression in a mouse model of chronic unpredictable mild
      stress (CUMS). The results showed that serum RPTN levels were significantly
      diminished in patients with schizophrenia and bipolar disorder or in
      psychostimulant users, compared with healthy subjects (n = 115) or age-matched
      controls (n = 92) (p < 0.0001). In CUMS mice, RPTN expression in hippocampus and
      prefrontal cortex was reduced with progression of the CUMS procedure; the serum
      RPTN level remained unchanged. Since CUMS is a model for depression and
      methamphetamine (METH) abuse induced psychosis recapitulates many of the
      psychotic symptoms of schizophrenia, the results from this study may imply that
      RPTN plays a potential role in emotional and cognitive processing; its decrease
      in serum may indicate its involvement in the pathogenesis of schizophrenia and
      bipolar disorder. 

PMID- 25613295
TI  - Neutral position of persistent direction-changing positional nystagmus.
AB  - The aim of this study was to measure the neutral position of direction-changing
      apogeotropic positional nystagmus (heavy cupula of the horizontal semicircular
      canal) and persistent direction-changing geotropic positional nystagmus (light
      cupula of the horizontal semicircular canal). We conducted a prospective case
      series study on 31 patients with heavy cupula (12 males, 19 females; mean age,
      64.3 years) and 33 patients with light cupula (10 males, 23 females; mean age,
      60.9 years). We measured the angle of the neutral position in patients with heavy
      cupula (theta 1) and that in patients with light cupula (theta 2) using a large
      protractor. The mean value and standard deviation of theta 1 was 31.6 +/- 22.4
      degrees , minimum value was 5 degrees , and maximum value was 89 degrees . The
      mean value and standard deviation of theta 2 was 44.4 +/- 20.5 degrees , minimum
      value was 5 degrees , and maximum value was 85 degrees . theta 2 was
      significantly greater than theta 1 (p < 0.05). The neutral position varies
      widely. Some patients exhibit a great angle (more than 40 degrees ); therefore,
      examiners should make patients adopt a completely lateral position in the supine
      head roll test and should confirm the direction of nystagmus in order to avoid
      mistaking positional nystagmus for spontaneous nystagmus.

PMID- 25613296
TI  - Parotid injury due to penetrating and blast injury.

PMID- 25613297
TI  - The development and design of the European Board of Otorhinolaryngology-Head and
      Neck Surgery Examination (EBEORL-HNS).
AB  - The UEMS Otorhinolaryngology-Head and Neck Surgery section is a dedicated body
      formed to promote the standardisation and harmonisation of European
      Otorhinolaryngology (ORL). The European Examination Board of Otorhinolaryngology
      and Head and Neck Surgery was created to establish a supranational final exam and
      accreditation for ORL Surgeons. It is open to candidates both from the European
      Union and outside the EU. The exam is composed of a written examination to assess
      mainly the theoretical knowledge of Otorhinolaryngological diseases. The second
      part, a viva voce examination, is designed to test the clinical application of
      knowledge based on case scenarios and clinical conditions presented to the
      candidates. The inaugural examination written component took place in
      Mannheim/Germany in 2009 and the inaugural Viva Voce examination in
      Vienna/Austria in 2010. Up to and including the year 2013, 858 participants have
      attempted one of the two exam components. Of the 858 participants, 305 were
      successful in both examinations and obtained the accreditation of the European
      Diploma (European Board Certification). The historical origins, development of
      the examination, its formal arrangements and the format of the examination are
      presented in this article.

PMID- 25613298
TI  - Mobile health technology for personalized primary care medicine.

PMID- 25613299
TI  - Novel treatments for idiopathic pulmonary fibrosis.

PMID- 25613300
TI  - Primary sellar melanocytic tumor mimicking hemorrhagic pituitary macroadenoma:
      Case report and literature review.
AB  - Primary melanocytic tumors of the central nervous system (CNS) are rare lesions,
      but primary sellar tumors are rarer. Only 10 cases have been reported, and they
      are often misdiagnosed as pituitary macroadenoma. We report the case of a 54-year
      old Chinese man who developed progressive bitemporal hemianopsia and visual loss.
      Magnetic resonance imaging (MRI) revealed an intrasellar and suprasellar clouded
      lesion adhering to the optic chiasm, hypothalamus, and hypophyseal stalk that was
      suspected of being a hemorrhagic pituitary macroadenoma. Because of the
      atypically giant, hemorrhagic, and upward-growing lesion, an initial trans
      sphenoidal approach failed, and subsequent transfrontal craniotomy was adopted to
      achieve macroscopically complete resection. Histopathologic findings revealed a
      benign melanocytic tumor. Despite an extensive search, no other primary or
      secondary site was found. Considering the relatively benign lesion, effective
      surgery, and potential significant consequences of radiotherapy, the patient
      received no further treatment and is still alive at the 7-year follow-up. Primary
      sellar melanocytic tumors are exceptional lesions that are difficult to diagnose
      before operating and/or obtaining pathological findings. The pathological
      classification and extent of surgical resection may play a key role in the
      prognosis. Once this type of lesion is suspected, the transfrontal approach may
      achieve preferable exposure and resection. Complete surgical resection may be
      sufficient for relatively benign lesions; otherwise, stereotactic fractionated
      radiotherapy is indicated. More cases should be reported to improve the treatment
      strategy. 

PMID- 25613301
TI  - New pregnane glycoside derivative from Caralluma retrospiciens (Ehrenb).
AB  - Retrospinoside (1) is a new polyoxy pregnane glycoside which was isolated and
      characterised from the aerial parts of Caralluma retrospiciens (Ehrenb.) N. E.
      Br., family Apocynaceae. The structure was established as 3-O-[beta-D
      glucopyranosyl-(1 -> 4)-beta-D-(3-O-methyl-6-desoxygalactopyranosy)]-14,15,20
      trihydroxy-4beta-pregnane. Its structural elucidation was performed through
      extensive spectroscopic measurements including 1D- and 2D-NMR, and HRMS, in
      addition to chemical methods. 

PMID- 25613302
TI  - Pharmacology of acid-sensing ion channels - Physiological and therapeutical
      perspectives.
AB  - Development of the pharmacology of Acid-Sensing Ion Channels (ASICs) has become a
      key challenge to study their structure, their molecular and cellular functions
      and their physiopathological roles. This review provides a summary of the
      different compounds that directly interact with these channels, either with
      inhibitory or stimulatory effect, and with high selectivity or poor specificity.
      They include drugs and endogenous regulators, natural compounds of vegetal
      origin, and peptides isolated from animal venoms. The in vivo use of some of
      these pharmacological modulators in animal models and a few small clinical
      studies in humans have provided substantial data on the physiological and
      physiopathological roles of ASIC channels. Modulation of these channels will
      certainly provide new therapeutic opportunities in neurological and psychiatric
      diseases including pain, stroke, epilepsy, anxiety, depression or traumatic
      injury, as well as in some non-neurological pathologies. This article is part of
      the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25613303
TI  - The consequences of suggesting false childhood food events.
AB  - We combined data across eight published experiments (N=1369) to examine the
      formation and consequences of false autobiographical beliefs and memories. Our
      path models revealed that the formation of false autobiographical belief fully
      mediated the pathway between suggesting to people that they had experienced a
      positive or negative food-related event in the past and current preference for
      that food. Suggestion indirectly affected intention to eat the food via change in
      autobiographical belief. The development of belief with and without memory
      produced similar changes in food preferences and behavior intention, indicating
      that belief in the event drives changes in suggestion-related attitudes. Finally,
      positive suggestions (e.g., "you loved asparagus the first time you tried it")
      yielded stronger effects than negative suggestions (e.g., "you got sick eating
      egg salad"). These findings show that false autobiographical suggestions lead to
      the development of autobiographical beliefs, which in turn, have consequences for
      one's attitudes and behaviors. 

PMID- 25613304
TI  - Deep-tissue oxygen monitoring in the brain of rabbits for stroke research.

PMID- 25613306
TI  - Thrombolysis in pediatric stroke study.

PMID- 25613305
TI  - Genetic overlap between diagnostic subtypes of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Despite moderate heritability, the phenotypic
      heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses
      of diagnostic subtypes with reduced sample sizes. We assessed evidence for a
      shared genetic basis among the 3 major subtypes: large artery atherosclerosis
      (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross
      subtype analyses. METHODS: Analyses used genome-wide summary data for 12 389
      ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and
      62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls,
      individual-level genotype data were also available. Genetic correlations between
      subtypes were estimated using linear mixed models and polygenic profile scores.
      Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls)
      was performed to identify shared risk alleles. RESULTS: High genetic correlation
      was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47,
      P=9*10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93).
      Between LAA and cardioembolism and SVD and cardioembolism, correlation was
      moderate using linear mixed models but not significantly different from zero for
      profile scoring. Joint meta-analysis of LAA and SVD identified strong association
      (P=1*10(-7)) for single nucleotide polymorphisms near the opioid receptor MU1
      (OPRM1) gene. CONCLUSIONS: Our results suggest that LAA and SVD, which have been
      hitherto treated as genetically distinct, may share a substantial genetic
      component. Combined analyses of LAA and SVD may increase power to identify small
      effect alleles influencing shared pathophysiological processes.

PMID- 25613309
TI  - WT1 enhances proliferation and impedes apoptosis in KRAS mutant NSCLC via
      targeting cMyc.
AB  - BACKGROUND: A novel link between oncogenic KRAS signalling and WT1 was recently
      identified. We sought to investigate the role of WT1 and KRAS in proliferation
      and apoptosis. METHODS: KRAS mutations and WT1 (cMyc) expression were detected
      using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung
      cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid
      and siRNA via transient transfection technology in H1299 and H1568 cells. MTT
      assay for detection of cell proliferation, and TUNEL assay and proteomic profiler
      assay for apoptosis evaluation were carried out. Dual luciferase reporter assay
      and ChIP-PCR were performed to validate the effect of WT1 on the cMyc promoter.
      RESULTS: KRAS mutations showed a negative impact on overall survival (OS). High
      expressions of WT1 and cMyc were associated with poor OS in KRAS mutant subgroup.
      The potential mechanisms that WT1 promotes proliferation and impedes apoptosis
      through affecting multiple apoptosis-related regulators in KRAS mutant NSCLC
      cells were identified. WT1 could activate cMyc promoter directly in KRAS mutant
      cells. CONCLUSION: The results suggest that WT1 and c-MYC expression is important
      for survival in KRAS mutant tumors as opposed to KRAS wild-type tumors. For
      treatment of KRAS mutant NSCLC, targeting WT1 and cMyc may provide alternative
      therapeutic strategies.

PMID- 25613307
TI  - Effect of patching on reducing restenosis in the carotid revascularization
      endarterectomy versus stenting trial.
AB  - BACKGROUND AND PURPOSE: The purpose is to determine whether patching during
      carotid endarterectomy (CEA) affects the perioperative and long-term risks of
      restenosis, stroke, death, and myocardial infarction as compared with primary
      closure. METHODS: We identified all patients who were randomized and underwent
      CEA in Carotid Revascularization Endarterectomy versus Stenting Trial. CEA
      patients who received a patch were compared with patients who underwent CEA with
      primary closure without a patch. We compared periprocedural and 4-year event
      rates, 2-year restenosis rates, and rates of reoperation between the 2 groups. We
      further analyzed results by surgeon specialty. RESULTS: There were 1151 patients
      who underwent CEA (753 [65%] with patch and 329 [29%] with primary closure). We
      excluded 44 patients who underwent eversion CEA and 25 patients missing CEA data
      (5%). Patch use differed by surgeon specialty: 89% of vascular surgeons, 6% of
      neurosurgeons, and 76% of thoracic surgeons patched. Comparing patients who
      received a patch versus those who did not, there was a significant reduction in
      the 2-year risk of restenosis, and this persisted after adjustment by surgeon
      specialty (hazard ratio, 0.35; 95% confidence interval, 0.16-0.74; P=0.006).
      There were no significant differences in the rates of periprocedural stroke and
      death (hazard ratio, 1.58; 95% confidence interval, 0.33-7.58; P=0.57), in
      immediate reoperation (hazard ratio, 0.6; 95% confidence interval, 0.16-2.27;
      P=0.45), or in the 4-year risk of ipsilateral stroke (hazard ratio, 1.23; 95%
      confidence interval, 0.42-3.63; P=0.71). CONCLUSIONS: Patch closure in CEA is
      associated with reduction in restenosis although it is not associated with
      improved clinical outcomes. Thus, more widespread use of patching should be
      considered to improve long-term durability. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

PMID- 25613310
TI  - Effect of allogeneic limbal mesenchymal stem cell therapy in corneal healing:
      role of administration route.
AB  - AIMS: To investigate whether allogeneic limbal mesenchymal stem cell (LMSC)
      therapy affects corneal healing after a severe chemical burn and whether the
      route of administration of LMSCs differs in its therapeutic effect in this
      respect. METHODS: A total of 60 Sprague-Dawley rats with clinically proven alkali
      injury were divided into four equal groups (n = 15) as follows: group 1: 2 *
      10(5) cells/drop LMSCs, topically applied 6 times a day for 2 days; group 2: 2.4
      * 10(6) cells in 0.5 ml LMSCs, subconjunctivally applied; group 3: 2.4 * 10(6)
      cells in 1 ml LMSCs, intraperitoneally applied, and group 4: no LMSC treatment.
      The groups were compared according to grades of corneal opacity (CO), corneal
      neovascularization (CNV) and corneal fluorescein staining (CFS). The migration of
      LMSCs into the cornea and the inflammatory characteristics of the groups were
      evaluated with BrdU (5-bromo-2'-deoxyuridine bromodeoxyuridine) immunostaining
      and histopathologically in a 4-week follow-up. RESULTS: There were statistically
      significant differences between the LMSC-treated and control groups in each week
      regarding mean CO scores and in the 3rd week regarding the mean CNV and CFS
      scores (p < 0.05). The statistical significance was due to the differences
      between the topical and the control group and between the subconjunctival and the
      control group. BrdU+ LMSCs were seen in the corneal epithelium of the all LMSC
      administered rats, and fewer inflammatory changes were observed in these rats.
      CONCLUSION: Allogeneic LMSC treatment, especially topical and subconjunctival
      administration, seems to be helpful in affecting corneal healing after a severe
      corneal burn.

PMID- 25613308
TI  - Alteplase for acute ischemic stroke: outcomes by clinically important subgroups
      in the Third International Stroke Trial.
AB  - BACKGROUND AND PURPOSE: Our aim was to identify whether particular subgroups of
      patients had an unacceptably high risk of symptomatic intracranial hemorrhage or
      low chance of benefit when treated with alteplase (recombinant tissue-type
      plasminogen activator). METHODS: Third International Stroke Trial was an
      international randomized trial of the intravenous (IV) recombinant plasminogen
      activator alteplase (0.9 mg/kg) versus control in 3035 (1515 versus 1520)
      patients. We analyzed the effect of recombinant tissue-type plasminogen activator
      on 6-month functional outcome, early death, and symptomatic intracranial
      hemorrhage (both <=7 days). We tested for any differences in treatment effect
      between subgroups by a test of interaction. Our 13 protocol prespecified
      subgroups were time to randomization, age, sex, stroke subtype, atrial
      fibrillation, early ischemic change (clinician and expert panel), prior
      antiplatelet use, stroke severity, diastolic and systolic blood pressure at
      randomization, center's thrombolysis experience, and trial phase. Analyses were
      adjusted for key baseline prognostic factors. RESULTS: There were no significant
      interactions in the subgroups analyzed that were consistent across all 3
      outcomes. Treatment with recombinant tissue-type plasminogen activator increased
      the odds of symptomatic intracranial hemorrhage by a greater amount in patients
      taking prior antiplatelets than those who were not (P=0.019 for test of
      interaction), but had no clear detrimental effect on functional outcome at 6
      months in this group (P=0.781 for test of interaction). CONCLUSIONS: Among the
      types of patient in the Third International Stroke Trial, this secondary analysis
      did not identify any subgroups for whom treatment should be avoided. Given the
      limitations of the analysis, we found no clear evidence to avoid treatment in
      patients with prior ischemic stroke, diabetes mellitus, or hypertension. CLINICAL
      TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier:
      ISRCTN25765518. http://www.controlled-trials.com/ISRCTN25765518.

PMID- 25613311
TI  - Inherited susceptibility to pancreatic cancer in the era of next-generation
      sequencing.

PMID- 25613312
TI  - The changing liver transplant waitlist: an emerging liver purgatory?

PMID- 25613313
TI  - Hunger games: is your stomach making you fat?

PMID- 25613314
TI  - Identifying molecular targets to improve immune function in alcoholic hepatitis.

PMID- 25613315
TI  - Impaired autophagy triggers chronic pancreatitis: lessons from pancreas-specific
      atg5 knockout mice.

PMID- 25613316
TI  - A comparison of the pharmacokinetics of three different preparations of total
      flavones of Hippophae rhamnoides in beagle dogs after oral administration.
AB  - Pharmacokinetic properties of isorhamnetin, quercetin, and kaempferol in three
      different total flavones of Hippophae rhamnoides (TFH) preparations were compared
      after oral administration to beagle dogs by a UPLC-MS method. The pharmacokinetic
      results showed that C max of isorhamnetin and quercetin in TFH solid dispersion
      (TFH-SD) and TFH self-emulsifying (TFH-SE) preparations was significantly
      enhanced than that in TFH preparations (p < 0.05). The AUCs of isorhamnetin and
      quercetin in TFH-SD were 5.9- and 3.1-fold higher than that of TFH, while the
      AUCs of isorhamnetin and quercetin in TFH-SE were 3.4- and 2.4-fold higher than
      that of TFH. These findings suggested that the oral bioavailability of
      isorhamnetin and quercetin in beagle dogs can be significantly increased in TFH
      SD and TFH-SE preparations compared to TFH preparations, which was helpful to
      explore the new forms for oral administration TFH and explain their in vivo
      processes. 

PMID- 25613317
TI  - Isosmotic points and their ecological significance for juvenile Chinese sturgeon
      Acipenser sinensis.
AB  - Serum osmolality and ion concentrations were measured in juvenile Chinese
      sturgeon Acipenser sinensis at different salinities to determine the isosmotic
      point. Isosmotic and isoionic concentrations were calculated from the regressions
      for serum and ambient osmolality, with Na(+) , Cl(-) and K(+) as salinities 9.19,
      8.17, 7.89 and 9.70, respectively. These values were consistent with the salinity
      of the habitat where juvenile A. sinensis occur in the Yangtze Estuary,
      suggesting that an isosmotic salinity is an important factor driving their
      habitat choice. 

PMID- 25613318
TI  - Intrauterine insemination of cultured peripheral blood mononuclear cells prior to
      embryo transfer improves clinical outcome for patients with repeated implantation
      failures.
AB  - Implantation failure is a major limiting factor in assisted reproduction
      improvement. Dysfunction of embryo-maternal immuno-tolerance pathways may be
      responsible for repeated implantation failures. This fact is supported by
      immunotropic theory stipulating that maternal immune cells, essentially uterine
      CD56+ natural killer cells, are determinants of implantation success. In order to
      test this hypothesis, we applied endometrium immuno-modulation prior to fresh
      embryo transfer for patients with repeated implantation failures. Peripheral
      blood mononuclear cells were isolated from repeated implantation failure patients
      undergoing assisted reproductive technology cycles. On the day of ovulation
      induction, cells were isolated and then cultured for 3 days and transferred into
      the endometrium cavity prior to fresh embryo transfer. This immunotherapy was
      performed on 27 patients with repeated implantation failures and compared with
      another 27 patients who served as controls. Implantation and clinical pregnancy
      were increased significantly in the peripheral blood mononuclear cell test versus
      control (21.54, 44.44 vs. 8.62, 14.81%). This finding suggests a clear role for
      endometrium immuno-modulation and the inflammation process in implantation
      success. Our study showed the feasibility of intrauterine administration of
      autologous peripheral blood mononuclear cells as an effective therapy to improve
      clinical outcomes for patients with repeated implantation failures and who are
      undergoing in vitro fertilization cycles. 

PMID- 25613319
TI  - Neuropsychological test performance in social anxiety disorder.
AB  - BACKGROUND: The effect of state factors on neuropsychological performance in
      social anxiety disorder (SAD) has not been thoroughly investigated and the
      overall neuropsychological profile remains poorly understood. AIMS: The primary
      objective of the study was to investigate the effect of state anxiety and state
      emotion suppression on neuropsychological performance in SAD. METHODS: A
      neuropsychological test battery was administered before and after an anxiety
      manipulation (instruction to give a video-recorded speech) to 42 patients with
      SAD and to a gender and education matched group of 42 healthy controls (HCs).
      RESULTS: Overall, participants with SAD performed worse than HCs on processing
      speed, visuospatial construction, visuospatial memory, verbal learning and word
      fluency, of which only the decreased visuospatial construction performance was
      considered clinically significant. State anxiety was not associated with
      neuropsychological performance at baseline, whereas state emotion suppression
      predicted decreased visuospatial memory in HCs and decreased verbal learning in
      the SAD group. Both groups performed better on working memory, processing speed
      and spatial anticipation, and worse on verbal learning and memory following the
      anxiety manipulation. The increase in state anxiety was associated with the
      decrease in verbal learning in both groups. CONCLUSIONS: Participants with SAD
      showed clinically significant difficulties with visuospatial construction and may
      experience verbal learning difficulties when suppressing emotions and
      experiencing an increase in anxiety.

PMID- 25613320
TI  - Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug
      delivery.
AB  - We report here a hepatoma-targeting multi-responsive biodegradable crosslinked
      nanogel, poly(6-O-vinyladipoyl-D-galactose-ss-N-vinylcaprolactam-ss-methacrylic
      acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and
      emulsion copolymerization for intracellular drug delivery. The nanogel exhibited
      redox, pH and temperature-responsive properties, which can be adjusted by varying
      the monomer feeding ratio. Furthermore, the volume phase transition temperature
      (VPTT) of the nanogels was close to body temperature and can result in rapid
      thermal gelation at 37  degrees C. Scanning electron microscopy also revealed
      that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With
      pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel
      degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an
      amorphous property of DOX within the nanogel, which was used in this study as a
      model anti-cancer drug. Drug-releasing characteristics of the nanogel were
      examined in vitro. The results showed multi-responsiveness of DOX release by the
      variation of environmental pH values, temperature or the availability of GSH, a
      biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor
      activity of the galactose-functionalized DOX-loaded nanogels against human
      hepatoma HepG2 cells, which was, at least in part, due to specific binding
      between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in
      hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric
      profiles further confirmed elevated cellular uptake of DOX by the galactose
      functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA)
      nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery.

PMID- 25613322
TI  - Walking can be more effective than balance training in fall prevention among
      community-dwelling older adults.
AB  - AIM: To examine the effects of walking on falls among community-dwelling older
      adults while accounting for exposures. METHODS: A total of 90 older adults,
      ranging in age from 65 to 79 years, were allocated into either the walking (brisk
      walking, n = 50) or the balance (balance and strength training, n = 40) group to
      participate in a 3-month supervised and 13-month unsupervised fall-prevention
      program held from 2012 to 2014 in Japan. Falls and trips that occurred during the
      16-month period were monitored with a monthly fall calendar. The risk of falls
      and trips was evaluated by person-year, physically active person-day and person
      step. RESULTS: The walking group showed a significant reduction in the fall risk
      when evaluated by the falls per physically active person-day (rate ratio 0.38,
      95% confidence interval 0.19-0.77) and falls per person-step (rate ratio 0.47,
      95% confidence interval 0.26-0.85) compared with the balance group. In contrast,
      the number of trips significantly increased with walking, even when evaluated as
      trips per physically active person-day (rate ratio 1.50, 95% confidence interval
      1.12-2.00). CONCLUSION: The present findings suggest that walking among community
      dwelling older adults can be more effective for fall prevention than balance
      training. However, because walking can induce more trips, walking should not be
      recommended for older adults who are susceptible to falling or frailty.

PMID- 25613323
TI  - Estimating the cognitive effects of prevalent diabetes, recent onset diabetes,
      and the duration of diabetes among older adults.
AB  - BACKGROUND: Little evidence is available on the effects of incident diabetes or
      diabetes duration on cognitive aging. METHODS: We evaluated the effects of
      prevalent and incident diabetes on deteriorations in cognitive function, based on
      participants (n = 8,671) aged 65+ in the Health and Retirement Study in 2000.
      Inverse probability weighting was used to account for selective attrition and
      time-varying confounding of incident diabetes. RESULTS: Prevalent diabetes
      predicted higher odds of dementia [odds ratio 1.27; 95% confidence interval (CI)
      1.03-1.58] and worse memory (-0.06 in z-score units; 95% CI -0.10 to -0.02), but
      incident diabetes or diabetes duration up to 8 years of follow-up was not
      predictive. CONCLUSION: Prevalent diabetes predicted lower cognition but not
      recent onset diabetes.

PMID- 25613321
TI  - Gene therapy restores vision in rd1 mice after removal of a confounding mutation
      in Gpr179.
AB  - The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice
      identified with a retinal degeneration. However, AAV-mediated gene
      supplementation of rd1 mice only results in structural preservation of
      photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in
      restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in
      Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with
      C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent
      with an autosomal recessive Mendelian inheritance pattern. We identify a mutation
      in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to
      the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid
      of the mutation in Gpr179 successfully restores the function of both
      photoreceptors and bipolar cells, which is maintained for up to 13 months. Our
      discovery may explain the failure of previous gene therapy attempts in rd1 mice,
      and we propose that Grp179 mutation status should be taken into account in future
      studies involving rd1 mice. 

PMID- 25613325
TI  - Next generation sequencing for characterizing biodiversity: promises and
      challenges.
AB  - DNA barcoding approaches are used to describe biodiversity by analysing specimens
      or environmental samples in taxonomic, phylogenetic and ecological studies. While
      sharing data among these disciplines would be highly valuable, this remains
      difficult because of contradictory requirements. The properties making a DNA
      barcode efficient for specimen identification or species delimitation are hardly
      reconcilable with those required for a powerful analysis of degraded DNA from
      environmental samples. The use of next generation sequencing methods open up the
      way towards the development of new markers (e.g., multilocus barcodes) that would
      overcome such limitations. However, several challenges should be taken up for
      coordinating actions at the interface between taxonomy, ecology, molecular
      biology and bioinformatics in order to develop methods and protocols compatible
      with both taxonomic and ecological studies. 

PMID- 25613324
TI  - Dissecting human skeletal muscle troponin proteoforms by top-down mass
      spectrometry.
AB  - Skeletal muscles are the most abundant tissues in the human body. They are
      composed of a heterogeneous collection of muscle fibers that perform various
      functions. Skeletal muscle troponin (sTn) regulates skeletal muscle contraction
      and relaxation. sTn consists of 3 subunits, troponin I (TnI), troponin T (TnT),
      and troponin C (TnC). TnI inhibits the actomyosin Mg(2+)-ATPase, TnC binds
      Ca(2+), and TnT is the tropomyosin (Tm)-binding subunit. The cardiac and skeletal
      isoforms of Tn share many similarities but the roles of modifications of Tn in
      the two muscles may differ. The modifications of cardiac Tn are known to alter
      muscle contractility and have been well-characterized. However, the modification
      status of sTn remains unclear. Here, we have employed top-down mass spectrometry
      (MS) to decipher the modifications of human sTnT and sTnI. We have extensively
      characterized sTnT and sTnI proteoforms, including alternatively spliced isoforms
      and post-translationally modified forms, found in human skeletal muscle with high
      mass accuracy and comprehensive sequence coverage. Moreover, we have localized
      the phosphorylation site of slow sTnT isoform III to Ser1 by tandem MS with
      electron capture dissociation. This is the first study to comprehensively
      characterize human sTn and also the first to identify the basal phosphorylation
      site for human sTnT by top-down MS. 

PMID- 25613326
TI  - Interactions of phthalates with preterm birth.

PMID- 25613327
TI  - Survival analysis in patients with ischemic stroke.

PMID- 25613328
TI  - Identifying effective medicinal plants for cold in Lorestan province, West of
      Iran.
AB  - Cold is a kind of mild and self-limiting viral illness that is considered as a
      prevalent disease with global occurrence and is caused by more than 200 types of
      viruses. Ethnobotanical studies and the use traditional experiences have
      increased the probability of detecting effective medicinal substances for cold by
      40%. This study aimed to identify effective medicinal plants for cold in Lorestan
      province. Traditional medical information of this work was obtained from
      information from indigenous people in 8 cities of Lorestan province. A previously
      prepared questionnaire was given to trained health liaisons to record the
      people's beliefs about the plants. The results showed that 23 medicinal plants
      were used in Lorestan province for treating cold and its symptoms (cough, sore
      throat, sneezing, runny nose, etc). Plants studied in this article contained
      bioactive substances that are recommended as the most popular traditional
      treatments. More research studies should be done on the efficacy and the
      potential harms of medicinal plants used by people, and in the case of their
      positive pharmacological impacts, they can be used to produce natural and
      effective drugs for cold. 

PMID- 25613329
TI  - Documentation of prescriptions and clinical outcomes in a homeopathic hospital
      setting in West Bengal, India.
AB  - Documentation of prescriptions and clinical outcomes in routine homeopathic
      practice is a prerequisite for conducting targeted research in homeopathy. Six
      homeopathic physicians participated in methodical data collection over a 3-month
      period in 6 outpatient departments of Mahesh Bhattacharyya Homeopathic Medical
      College and Hospital, West Bengal, India. A specifically designed Microsoft Excel
      spreadsheet enabled recording of consecutive appointments-date, patient identity,
      medical condition/complaint, whether chronic/acute, new/follow-up case, patient
      assessed outcome (7-point Likert-type scale: -3 to +3), prescribed homeopathic
      medication, and whether other medication/s being taken for the condition.
      Spreadsheets were submitted monthly for data synthesis and analysis. A total of
      1972 patients' follow-up generated data of 2905 appointments, of which 2272
      (78.2%) were positive, 183 (6.3%) negative, and 450 (15.5%) showed no change.
      Strongly positive outcomes (scores of +2/+3) were recorded in osteoarthritis,
      piles, cough, dysfunctional uterine bleeding, chronic suppurative otitis media,
      and conjunctivitis. This systematic recording short-listed promising areas of
      future homeopathic research. 

PMID- 25613330
TI  - Immunomodulatory Effects of Ethanolic Extract of Thyphonium flagelliforme (Lodd)
      Blume in Rats Induced by Cyclophosphamide.
AB  - The present study aimed to examine the immunomodulatory effect of ethanolic
      extract of Typhonium flagelliforme (Lodd) Blume in cyclophosphamide-treated rats.
      The immunomodulatory effects were determined by lymphocytes proliferation,
      phagocytic activity of macrophages, plasma cytokines of tumor necrosis factor
      alpha, interleukin-1alpha, interleukin-10 levels, and killer T cells (CD8+ T
      cells) counts. The results showed that the administration of ethanolic extract of
      T flagelliforme reduced immunosupessive effect on lymphocyte proliferation,
      increase the number and phagocytic activity of macrophages in cyclophosphamide
      treated rats. Moreover, the ethanolic extract of T flagelliforme also
      significantly (P < .05) improved the immune system activities especially the
      proliferation of CD8+T cells and reduced the suppressive effects on cytokines
      such as tumor necrosis factor-alpha and interleukin-1alpha. In conclusion, the
      ethanolic extract of T flagelliforme has immunomodulatory properties in
      cyclophosphamide-treated rats. The results suggest that T flagelliforme can
      reduce immunosuppresive effect caused by a chemotherapeutic agent. 

PMID- 25613331
TI  - Integration of a Kampo medicine, Nijutsuto, and Western medical treatment in the
      treatment of long-term frozen shoulder refractory to Western medical treatment: a
      case series.
AB  - OBJECTIVE: Frozen shoulder is a common disorder in general orthopedic practice,
      characterized by spontaneous onset of pain in the shoulder and accompanied by
      limitation of glenohumeral movement. Treatments for frozen shoulder include
      shoulder exercise, manual therapy, corticosteroid injection, manipulation under
      anesthesia, and arthroscopic capsular release. Several patients suffer from some
      degree of pain and range of motion limitation for up to 10 years even when these
      treatments are applied. Kampo, a traditional Japanese herbal medicine based on
      traditional Chinese herbal medicine, has been used for the treatment of pain in
      Japan. Nijutsuto has been a Kampo formula used to effectively treat frozen
      shoulder. METHODS: Thirteen patients suffering from long-term frozen shoulder
      refractory to Western medical treatment were administered Nijututo. RESULTS:
      Almost all patients experienced sound pain relief after Nijutsuto admnistration.
      There were no severe side effects reported. CONCLUSION: Nijutsuto combined with
      an exercise program improved pain intensity in 13 patients with long-term frozen
      shoulder.

PMID- 25613332
TI  - Gadoxetic acid: pearls and pitfalls.
AB  - Gadoxetic acid is a hepatocyte-specific magnetic resonance imaging contrast agent
      with the ability to detect and characterize focal liver lesions and provide
      structural and functional information about the hepatobiliary system. Knowledge
      of the pharmacokinetics of gadoxetic acid is paramount to understanding imaging
      protocol and lesion appearance and facilitates identification and avoidance of
      undesired effects with use of this intravenous contrast agent. This article
      reviews the utility of gadoxetic acid in liver and biliary imaging, with emphasis
      on the hepatobiliary phase. 

PMID- 25613333
TI  - The "bear paw" sign.

PMID- 25613334
TI  - Improving the detection of small lesions using a state-of-the-art time-of-flight
      PET/CT system and small-voxel reconstructions.
AB  - A major disadvantage of (18)F-FDG PET involves poor detection of small lesions
      and lesions with low metabolism, caused by limited spatial resolution and
      relatively large image voxel size. As spatial resolution and sensitivity are
      better in new PET systems, it is expected that small-lesion detection could be
      improved using smaller voxels. The aim of this study was to test this hypothesis
      using a state-of-the-art time-of-flight PET/CT device. METHODS: (18)F-FDG PET
      scans of 2 image-quality phantoms (sphere sizes, 4-37 mm) and 39 consecutive
      patients with lung cancer were analyzed on a time-of-flight PET/CT system. Images
      were iteratively reconstructed with standard 4 * 4 * 4 mm voxels and smaller 2 *
      2 * 2 mm voxels. For the phantom study, we determined contrast-recovery
      coefficients and signal-to-noise ratios (SNRs). For the patient study, (18)F-FDG
      PET-positive lesions in the chest and upper abdomen with a volume less than 3.0
      mL (diameter, <18 mm) were included. Lesion mean and maximum standardized uptake
      values (SUVmean and SUVmax, respectively) were determined in both image sets.
      SNRs were determined by comparing SUVmax and SUVmean with background noise
      levels. A subanalysis was performed for lesions less than 0.75 mL (diameter, <11
      mm). For qualitative analysis of patient data, 3 experienced nuclear medicine
      physicians gave their preference after visual side-by-side analysis. RESULTS: For
      phantom spheres 13 mm or less, we found higher contrast-recovery coefficients and
      SNRs using small-voxel reconstructions. For 66 included (18)F-FDG PET-positive
      lesions, the average increase in SUVmean and SUVmax using the small-voxel images
      was 17% and 32%, respectively (P < 0.01). For lesions less than 0.75 mL (21 in
      total), the average increase was 21% and 44%, respectively. Moreover, averaged
      over all lesions, the mean and maximum SNR increased by 20% and 27%, respectively
      (P < 0.01). For lesions less than 0.75 mL, these values increased up to 23% and
      46%, respectively. The physicians preferred the small-voxel reconstructions in
      76% of cases. CONCLUSION: Supported by a phantom study, there was a visual
      preference toward (18)F-FDG PET images reconstructed with 2 * 2 * 2 mm voxels and
      a profound increase in standardized uptake value and SNR for small lesions.
      Hence, it is expected that small-lesion detection improves using small-voxel
      reconstructions.

PMID- 25613335
TI  - Development of consensus statements for pregnancy screening in diagnostic nuclear
      medicine: a Delphi study.
AB  - Current radiation protection recommendations do not provide clear guidelines or
      advice on pregnancy screening strategies for diagnostic nuclear medicine
      procedures. Previous studies have reported on variations in current practice for
      pregnancy screening before diagnostic nuclear medicine procedures. The
      development of consensus statements aims to provide a consistent approach and
      assist nuclear medicine personnel to confidently question patients about their
      pregnancy status. METHODS: The Delphi technique was chosen for the research
      design. A panel consisting of 10 experienced nuclear medicine personnel from
      Australia and New Zealand was recruited. Panel members were provided with a
      summary of existing research. Consensus agreement was predefined as 80%.
      Questionnaires were developed and distributed to the panel members, with
      iterative analysis and feedback between survey rounds. Three survey rounds were
      conducted online using SurveyMonkey between December 2013 and June 2014. The
      round 1 questionnaire was developed from the results of a previous survey. It
      consisted of 30 questions designed to gather the opinions of the expert panel.
      After analysis of the round 1 responses, consensus statements were developed for
      round 2 and revised in round 3. RESULTS: Consensus was achieved for 16
      statements. The statements recommend using verbal questioning with patient
      signature, defining the age range for questioning as 12-55 y, providing advice on
      the use of pregnancy testing, and questioning potentially difficult groups such
      as teenagers. A flowchart was included for comment in round 3. CONCLUSION: This
      was the first Australian study to develop consensus statements and a flowchart to
      assist nuclear medicine personnel in consistently and confidently questioning
      patients about their pregnancy status before diagnostic procedures.
      Implementation of these statements into clinical practice guidelines should
      reduce the possibility of inadvertent fetal irradiation.

PMID- 25613336
TI  - How to write a protocol: part 1.
AB  - Clinical imaging protocols play an important role in the provision of high
      quality care in nuclear medicine. It is imperative that all nuclear medicine
      facilities have protocols for every procedure performed. However, creating
      protocols that are detailed, unambiguous, and consistent is often easier said
      than done. Properly written protocols help to ensure that nuclear medicine
      procedures are performed in a standardized, reproducible manner so that patients
      receive high-quality care. This 2-part article provides technologists with a
      framework for composing comprehensive protocols. Part 1 discusses the secrets to
      successfully composing protocols ensuring they are detailed and step-by-step
      along with the importance of basing protocols on evidence from published
      guidelines and peer-reviewed literature. The components and important aspects of
      clinical imaging protocols are detailed. 

PMID- 25613337
TI  - Minimizing patient-specific tracer dose in myocardial perfusion imaging using CZT
      SPECT.
AB  - Myocardial perfusion imaging (MPI) with SPECT is widely adopted in clinical
      practice but is associated with a relatively high radiation dose. The aim of this
      study was to determine the minimum product of tracer dose and scan time that will
      maintain diagnostic value for cadmium zinc telluride (CZT) SPECT MPI. METHODS:
      Twenty-four patients underwent clinically indicated stress MPI using CZT SPECT
      and a body weight-dependent (3 MBq/kg) (99m)Tc-tetrofosmin tracer dose. Data were
      acquired for 8 min in list mode. Next, images were reconstructed using 2-, 4-, 6
      , and 8-min time frames. Differences between the 8-min reference scan and the
      shorter scans were determined in segmental uptake values (using the 17-segment
      cardiac model), ejection fraction, and end-diastolic volume. A 5% difference in
      segmental uptake was considered to significantly influence the diagnostic value.
      Next, the quality of the 4-, 6-, and 8-min scans was scored on a 4-point scale by
      consensus by 3 experienced nuclear medicine physicians. The physicians did not
      know the scan time or patient information. RESULTS: Differences in segmental
      uptake values, ejection fraction, and end-diastolic volume were greater for
      shorter scans than for the 8-min reference scan. On average, the diagnostic value
      was influenced in 7.7 segments per patient using the 2-min scans, in comparison
      to 2.0 and 0.8 segments per patient using the 4- and 6-min scans, respectively.
      In addition, the 4-min scans led to a significantly reduced image quality
      compared with the 8-min scans (P < 0.05). This was not the case for the 6-min
      scan. CONCLUSION: Six minutes was the shortest acquisition time in stress MPI
      using CZT SPECT that did not affect the diagnostic value for a tracer dose of 3
      MBq/kg. Hence, the patient-specific product of tracer dose and scan time can be
      reduced to a minimum of 18 MBq.min/kg, which may lower the effective radiation
      dose for patients to values below 1 mSv.

PMID- 25613338
TI  - Lesion detection performance: comparative analysis of low-dose CT data of the
      chest on two hybrid imaging systems.
AB  - Incidental findings on low-dose CT images obtained during hybrid imaging are an
      increasing phenomenon as CT technology advances. Understanding the diagnostic
      value of incidental findings along with the technical limitations is important
      when reporting image results and recommending follow-up, which may result in an
      additional radiation dose from further diagnostic imaging and an increase in
      patient anxiety. This study assessed lesions incidentally detected on CT images
      acquired for attenuation correction on two SPECT/CT systems. METHODS: An
      anthropomorphic chest phantom containing simulated lesions of varying size and
      density was imaged on an Infinia Hawkeye 4 and a Symbia T6 using the low-dose CT
      settings applied for attenuation correction acquisitions in myocardial perfusion
      imaging. Twenty-two interpreters assessed 46 images from each SPECT/CT system (15
      normal images and 31 abnormal images; 41 lesions). Data were evaluated using a
      jackknife alternative free-response receiver-operating-characteristic analysis
      (JAFROC). RESULTS: JAFROC analysis showed a significant difference (P < 0.0001)
      in lesion detection, with the figures of merit being 0.599 (95% confidence
      interval, 0.568, 0.631) and 0.810 (95% confidence interval, 0.781, 0.839) for the
      Infinia Hawkeye 4 and Symbia T6, respectively. Lesion detection on the Infinia
      Hawkeye 4 was generally limited to larger, higher-density lesions. The Symbia T6
      allowed improved detection rates for midsized lesions and some lower-density
      lesions. However, interpreters struggled to detect small (5 mm) lesions on both
      image sets, irrespective of density. CONCLUSION: Lesion detection is more
      reliable on low-dose CT images from the Symbia T6 than from the Infinia Hawkeye
      4. This phantom-based study gives an indication of potential lesion detection in
      the clinical context as shown by two commonly used SPECT/CT systems, which may
      assist the clinician in determining whether further diagnostic imaging is
      justified.

PMID- 25613339
TI  - A Monte Carlo study of the dependence of early frame sampling on uncertainty and
      bias in pharmacokinetic parameters from dynamic PET.
AB  - Compartmental modeling of dynamic PET data enables quantification of tracer
      kinetics in vivo, through the calculated model parameters. In this study, we
      aimed to investigate the effect of early frame sampling and reconstruction method
      on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias
      and uncertainty (SD). METHODS: The GATE Monte Carlo software was used to simulate
      2 * 15 dynamic 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) brain PET studies,
      typical in terms of noise level and kinetic parameters. The data were
      reconstructed by both 3-dimensional (3D) filtered backprojection with
      reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6
      dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15
      s. Bias and SD were evaluated for fitted parameter estimates, calculated from
      regions of interest. RESULTS: The 2-tissue-model parameter estimates K1, k2, and
      fraction of arterial blood in tissue depended on early frame sampling, and a
      sampling of 6-15 s generally minimized bias and SD. The shortest sampling of 1 s
      yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM,
      respectively, and a parameter uncertainty that was 10%-70% higher. The schemes
      from 4 to 15 s were generally not significantly different in regards to bias and
      SD. Typically, the reconstruction method 3DRP yielded less frame-sampling
      dependence and less uncertain results, compared with OSEM, but was on average
      more biased. CONCLUSION: Of the 6 sampling schemes investigated in this study, an
      early frame duration of 6-15 s generally kept both bias and uncertainty to a
      minimum, for both 3DRP and OSEM reconstructions. Very-short frames of 1 s should
      be avoided because they typically resulted in the largest parameter bias and
      uncertainty. Furthermore, 3DRP may be preferred over OSEM for short frames with
      poor statistics.

PMID- 25613341
TI  - Early steps in the European eel (Anguilla anguilla)-Vibrio vulnificus interaction
      in the gills: role of the RtxA13 toxin.
AB  - Vibrio vulnificus is an aquatic gram-negative bacterium that causes a systemic
      disease in eels called warm-water vibriosis. Natural disease occurs via water
      born infection; bacteria attach to the gills (the main portal of entry) and
      spread to the internal organs through the bloodstream, provoking host death by
      haemorrhagic septicaemia. V. vulnificus produces a toxin called RtxA13 that
      hypothetically interferes with the eel immune system facilitating bacterial
      invasion and subsequent death by septic shock. The aim of this work was to study
      the early steps of warm-water vibriosis by analysing the expression of three
      marker mRNA transcripts related to pathogen recognition (tlr2 and tlr5) and
      inflammation (il-8) in the gills of eels infected by immersion with either the
      pathogen or a mutant deficient in rtxA13. Results indicate a differential
      response that is linked to the rtx toxin in the expression levels of the three
      measured mRNA transcripts. The results suggest that eels are able to distinguish
      innocuous from harmful microorganisms by the local action of their toxins rather
      than by surface antigens. Finally, the cells that express these transcripts in
      the gills are migratory cells primarily located in the second lamellae that re
      locate during infection suggesting the activation of a specific immune response
      to pathogen invasion in the gill. 

PMID- 25613340
TI  - Factors influencing the uptake of 99mTc-sestamibi in breast tissue on molecular
      breast imaging.
AB  - The purpose of this study was to evaluate the impact of changes to a patient's
      prandial status, metabolic status (rest vs. exercise), and peripheral blood flow
      (via caffeine or warming) on the uptake of (99m)Tc-sestamibi in breast tissue.
      METHODS: A total of 154 subjects participated in 1 of 4 study groups that
      evaluated the effects of 4 types of intervention on the uptake of (99m)Tc
      sestamibi in breast tissue (effect of fasting, light exercise, caffeine, and
      peripheral warming). Molecular breast imaging was performed before and after each
      intervention. Count density was assessed in counts/cm(2)/MBq from the
      mediolateral oblique view in all studies. RESULTS: Uptake of (99m)Tc-sestamibi in
      breast tissue increased by approximately 25% from 6.6 counts/cm(2)/MBq in the fed
      state to 8.3 counts/cm(2)/MBq with fasting. Peripheral warming also resulted in
      an approximately 20% increase in count density from 9.1 to 10.9 counts/cm(2)/MBq.
      Conversely, exercise caused a 35% drop in count density relative to the resting
      state. Uptake did not seem to be influenced by caffeine and did not correlate
      with a patient's height, weight, or breast thickness. There was only a weak
      correlation between breast activity and body surface area. CONCLUSION: The
      combined effects of fasting and warming resulted in an approximately 50%
      increased uptake of (99m)Tc-sestamibi in breast tissue relative to that observed
      in a reference group to whom no preparatory instructions had been given. Optimal
      patient preparation before administration of (99m)Tc-sestamibi should permit a
      corresponding reduction in either acquisition time or required dose of (99m)Tc
      sestamibi.

PMID- 25613342
TI  - Isolation and function analysis of apolipoprotein A-I gene response to virus
      infection in grouper.
AB  - Apolipoproteins, synthesized mainly in liver and intestine and bounded to lipids,
      play important roles in lipid transport and uptake through the circulation
      system. In this study, an apolipoprotein A-I gene homologue was cloned from
      orange-spotted grouper Epinephelus coioides (designed as Ec-ApoA-I) by rapid
      amplification of cDNA ends (RACE) PCR. The full-length cDNA of Ec-ApoA-I was
      comprised of 1278 bp with a 792 bp open reading frame (ORF) that encodes a
      putative protein of 264 amino acids. Quantitative real-time PCR (qPCR) analysis
      revealed that Ec-ApoA-I was abundant in liver and intestine, and the expression
      in liver was significantly (P < 0.01) up-regulated after the stimulation of LPS,
      Poly(I:C), Vibrio alginolyticus, and Singapore grouper iridovirus (SGIV).
      Recombinant Ec-ApoA-I (rEc-ApoA-I) was produced in Escherichia coli BL21 (DE3)
      expression system exhibited bacteriolyticactivity against Microcococcus
      lysodeikticus and Aeromonas hydrophila. Intracellular localization revealed that
      Ec-ApoA-I distributed in both cytoplasm and nucleus, and predominantly in the
      cytoplasm. Overexpression of Ec-ApoA-I in grouper Brain (GB) cells could inhibit
      the replication of SGIV. These results together indicated that Ec-ApoA-I perhaps
      is involved in the responses to bacterial and viral challenge. 

PMID- 25613343
TI  - [Suspicion of food contaminants in the occurrence of a fixed drug eruption in a
      child].

PMID- 25613344
TI  - Isolated tuberculous osteomyelitis of the talonavicular joint without pulmonary
      involvement-a rare case report.
AB  - Tuberculosis is one of the leading causes of death worldwide amongst curable
      diseases. It is estimated that one-third of the world's population has been
      diagnosed with tuberculosis infection [1]. The prevalence is on the rise with an
      estimated 9.4 million new cases per year worldwide [1]. Tuberculosis most
      commonly presents with pulmonary involvement. However, approximately 23-30% of
      patients found to be infected with tuberculosis have extrapulmonary symptoms [2].
      Of those, only 1-3% have been found to have osseous disease. Skeletal involvement
      with a primary focus of tuberculosis usually affects major weight-bearing joints
      such as the hip and knee. Tuberculosis infections of the foot and ankle are very
      rare, accounting for 1% of all tuberculosis infections [2-4]. Difficulties arise
      in the timing of diagnosis, patient compliance of therapy and awareness of the
      less obvious presenting symptoms. Musculoskeletal tuberculosis, although rare,
      can be a problem. Its uncommon site, non-specific presenting symptoms and its
      ability to mimic numerous disorders make it more difficult to formulate a
      definitive diagnosis and, in turn, leads to therapeutic delays [5-7]. It is for
      this reason that we report this case in an effort to promote awareness. 

PMID- 25613345
TI  - Effects of estradiol valerate and remifemin on norepinephrine signaling in the
      brain of ovariectomized rats.
AB  - AIMS: We investigated the norepinephrine pathway changes from the locus coeruleus
      (LC) to the preoptic area of the hypothalamus (POAH) in the brain of
      ovariectomized rats under low estrogen levels and explored the therapeutic
      effects of estradiol valerate (E2) and Remifemin (ICR) on these changes. METHODS:
      40 female Sprague-Dawley rats were randomly divided into the following groups:
      surgery with vehicle (SHAM), ovariectomy surgery with vehicle (OVX), ovariectomy
      with E2 treatment (OVX + E2), and ovariectomy with Remifemin (OVX + ICR). After 4
      weeks of treatment, we observed the changes by immunohistochemistry. RESULTS: (1)
      The average optical density of DBH-ir fibers and the number of alpha1
      adrenoreceptor- and estrogen receptor (ER)alpha-positive neurons in the main
      nuclei of POAH were all reduced in OVX rats compared with the SHAM group. The
      above changes were normalized in all nuclei of the POAH in the E2 group, while
      they were normalized in some nuclei in the ICR group. Coexpression of ERalpha and
      alpha1-adrenoreceptor was observed in the POAH. (2) The number of DBH- and
      ERalpha-positive neurons in the LC decreased in the OVX group compared with the
      SHAM group and increased after treatment with E2 and ICR. Coexpression of ERalpha
      and DBH was observed in the LC. CONCLUSION: Low estrogen (OVX) altered
      norepinephrine synthesis in the LC, the projection of norepinephrine fibers and
      alpha1-adrenoreceptor expression in the POAH. Both E2 and ICR normalized the
      norepinephrine pathway, but E2 achieved greater effects than ICR. ICR had
      different effects in different nuclei in the POAH and its therapeutic effect was
      better in the LC.

PMID- 25613346
TI  - Inter-epidemic abundance and distribution of potential mosquito vectors for Rift
      Valley fever virus in Ngorongoro district, Tanzania.
AB  - BACKGROUND: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that
      primarily affects ruminants but also has the capacity to infect humans.
      OBJECTIVE: To determine the abundance and distribution of mosquito vectors in
      relation to their potential role in the virus transmission and maintenance in
      disease epidemic areas of Ngorongoro district in northern Tanzania. METHODS: A
      cross-sectional entomological investigation was carried out before the suspected
      RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors
      using the Centre for Disease Control (CDC) light traps and Mosquito Magnets
      baited with attractants. Outdoor traps were placed in proximity with breeding
      sites and under canopy in banana plantations close to the sleeping places of
      animals. RESULTS: A total of 1,823 mosquitoes were collected, of which 87%
      (N=1,588) were Culex pipiens complex, 12% (N=226) Aedes aegypti, and 0.5% (N=9)
      Anopheles species. About two-thirds (67%; N=1,095) of C. pipiens complex and
      nearly 100% (N=225) of A. aegypti were trapped outdoors using Mosquito Magnets.
      All Anopheles species were trapped indoors using CDC light traps. There were
      variations in abundance of C. pipiens complex and A. aegypti among different
      ecological and vegetation habitats. Over three quarters (78%) of C. pipiens
      complex and most (85%) of the A. aegypti were trapped in banana and maize farms.
      Both C. pipiens complex and A. aegypti were more abundant in proximity with
      cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number
      of mosquitoes was recorded in villages that were most affected during the RVF
      epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of
      A. aegypti, none was infected with RVF virus. CONCLUSIONS: These results provide
      insights into unique habitat characterisation relating to mosquito abundances and
      distribution in RVF epidemic-prone areas of Ngorongoro district in northern
      Tanzania.

PMID- 25613347
TI  - Soft chemical control of superconductivity in lithium iron selenide hydroxides
      Li(1-x)Fe(x)(OH)Fe(1-y)Se.
AB  - Hydrothermal synthesis is described of layered lithium iron selenide hydroxides
      Li(1-x)Fe(x)(OH)Fe(1-y)Se (x ~ 0.2; 0.02 < y < 0.15) with a wide range of iron
      site vacancy concentrations in the iron selenide layers. This iron vacancy
      concentration is revealed as the only significant compositional variable and as
      the key parameter controlling the crystal structure and the electronic
      properties. Single crystal X-ray diffraction, neutron powder diffraction, and X
      ray absorption spectroscopy measurements are used to demonstrate that
      superconductivity at temperatures as high as 40 K is observed in the
      hydrothermally synthesized samples when the iron vacancy concentration is low (y
      < 0.05) and when the iron oxidation state is reduced slightly below +2, while
      samples with a higher vacancy concentration and a correspondingly higher iron
      oxidation state are not superconducting. The importance of combining a low iron
      oxidation state with a low vacancy concentration in the iron selenide layers is
      emphasized by the demonstration that reductive postsynthetic lithiation of the
      samples turns on superconductivity with critical temperatures exceeding 40 K by
      displacing iron atoms from the Li(1-x)Fe(x)(OH) reservoir layer to fill vacancies
      in the selenide layer.

PMID- 25613348
TI  - Oral and general health-related quality of life in patients treated for oral
      cancer compared to control group.
AB  - BACKGROUND: Health-related quality of life (HRQoL) is gaining importance as a
      valuable outcome measure in oral cancer area. The aim of this study was to assess
      the general and oral HRQoL of oral and oropharyngeal cancer patients 6 or more
      months after treatment and compare them with a population free from this disease.
      METHODS: A cross-sectional study was carried out with patients treated for oral
      cancer at least 6 months post-treatment and a gender and age group matched
      control group. HRQoL was measured with the 12-Item Short Form Health Survey (SF
      12); oral HRQoL (OHRQoL) was evaluated using the Oral Health Impact Profile (OHIP
      14) and the Oral Impacts on Daily Performances (OIDP). Multivariable regression
      models assessed the association between the outcomes (SF-12, OHIP-14 and OIDP)
      and the exposure (patients versus controls), adjusting for sex, age, social
      class, functional tooth units and presence of illness. RESULTS: For patients (n =
      142) and controls (n = 142), 64.1% were males. The mean age was 65.2 (standard
      deviation (sd): 12.9) years in patients and 67.5 (sd: 13.7) years in controls.
      Patients had worse SF-12 Physical Component Summary scores than controls even in
      fully the adjusted model [beta-coefficient = -0.11 (95% CI: -5.12-(-0.16)]. The
      differences in SF-12 Mental Component Summary were not statistically significant.
      Regarding OHRQoL patients had 11.63 (95% CI: 6.77-20.01) higher odds for the OHIP
      14 and 21.26 (95% CI: 11.54-39.13) higher odds for OIDP of being in a worse
      category of OHRQoL compared to controls in the fully adjusted model. CONCLUSION:
      At least 6 months after treatment, oral cancer patients had worse OHRQoL, worse
      physical HRQoL and similar psychological HRQoL than the general population.

PMID- 25613349
TI  - The retropulsion test: a good evaluation of postural instability in Parkinson's
      disease?
AB  - Postural instability is a disabling feature of Parkinson's disease (PD),
      contributing to recurrent falls and fall-related injuries. The retropulsion test
      is widely regarded as the gold standard to evaluate postural instability, and is
      therefore a key component of the neurological examination in PD. Many variants
      exist, which confuses both clinical practice and research. Here, we evaluate the
      merits of this test by discussing three common variants: (1) the pull test as
      described in the MDS-UPDRS scale; (2) using an unexpected shoulder pull, without
      prior warning; and (3) the push-and-release test. All variants are a quick method
      to index the degree of postural instability, but the outcome can vary
      considerably due to variability in test execution and -interpretation. This
      partially explains why the retropulsion test fails to predict future falls in PD.
      Another explanation is that falling results from the complex interplay between
      gait, balance, cognitive decline and environmental factors, and the retropulsion
      test captures only part of that. We conclude with several recommendations for
      current clinical practice. 

PMID- 25613350
TI  - Fatty acid composition of the anterior cingulate cortex indicates a high
      susceptibility to lipid peroxidation in Parkinson's disease.
AB  - BACKGROUND: Oxidative stress contributes to Parkinson's disease (PD) etiology.
      Although previous studies have focused on sources of free radical formation in
      brain regions affected by PD, less is known regarding changes in lipid
      composition and the implications for susceptibility to peroxidation. OBJECTIVE:
      To assess fatty acid profiles from control and PD tissues that are susceptible to
      PD pathology but devoid of severe destruction. METHODS: We used gas
      chromatography methods to assess fatty acid profiles from control (n = 10) and PD
      (n = 9) postmortem tissues. We focused on the anterior cingulate cortex (ACC), a
      region that accumulates alpha-synuclein, but does not undergo severe destruction,
      and compared this to the occipital cortex, a region that is pathologically
      spared. RESULTS: Our data indicate a significant 33% increase in the proportion
      of polyunsaturated fatty acids (mol%) present in the PD ACC as compared to
      control ACC. Increases in highly unsaturated 22:5n-6 and 22:6n-3 fatty acids were
      particularly pronounced (109% and 73%, respectively). Calculation of a
      peroxidation index (accounting for total fatty acyl double bounds) indicated a
      44% increase in susceptibility of the PD ACC to lipid peroxidation compared to
      control ACC. Such differences were not detected in the occipital cortex from the
      same donors. Assessment of F2-isprostane levels confirmed that PD tissue lipids
      were more oxidized than controls. CONCLUSIONS: The global composition of fatty
      acids in the PD ACC is altered in a way that increases susceptibility to
      peroxidation in a region-specific manner. This has important implications for PD,
      supporting the oxidative stress hypothesis of PD pathogenesis.

PMID- 25613351
TI  - Neuropsychological effects of deep brain stimulation in subjects with early stage
      Parkinson's disease in a randomized clinical trial.
AB  - BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for patients
      with advanced Parkinson's disease (PD) and motor symptom complications. Recently,
      attention has been focused on whether offering DBS earlier in the course of PD is
      beneficial. OBJECTIVE: The purpose of this study was to determine the effects of
      DBS on neuropsychological functioning in subjects with early stage PD. METHODS:
      Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were
      randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic
      nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent
      process specially designed for the study and administered by a medical ethicist
      and the study team. Comprehensive neuropsychological testing was completed in the
      treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups.
      RESULTS: Two serious adverse events occurred in the DBS+ODT group. One subject
      experienced a stroke and another developed infected hardware that contributed to
      specific declines in cognitive functioning. However, compared to the ODT group,
      the remaining subjects in the DBS+ODT group exhibited modest reductions on a few
      measures of attention, executive function, and word fluency at 12 months. These
      differences were largely diminished at 24 months, especially when those with the
      adverse events were excluded. CONCLUSIONS: The results of this trial provide
      novel data regarding the effects of DBS on cognitive function in early PD. We
      believe that the findings and insights from this trial can help guide the safety
      analysis and risk-benefit evaluations in future discussions of DBS in early stage
      PD.

PMID- 25613352
TI  - Regulation of chick Ebf1-3 gene expression in the pharyngeal arches, cranial
      sensory ganglia and placodes.
AB  - This study was conducted to identify the regulation of the expression of the
      cEbf1-3 (chick early B-cell factor 1-3) genes in the pharyngeal arches (PAs),
      cranial sensory ganglia and placodes. cEbf1 and cEbf3 were mainly expressed in
      the cranial neural crest cells (NCCs) occupying the PAs, but cEbf2 was expressed
      in the mesenchymal core. cEbf1-3 were prominently expressed in the olfactory
      placodes, but cEbf1 and cEbf3 were only expressed in the otic vesicle. cEbf1 was
      expressed in all cranial sensory ganglia, cEbf2 (only) in the dorsolateral
      ganglia and cEbf3 in the trigeminal and vestibular ganglia. The removal of the
      source (the cranial neural tube) of the cranial NCCs before their migration to
      the PAs led to downregulation of cEbf1 and cEbf3 and upregulation of cEbf2
      expression. Gain- and loss-of-function experiments showed that sonic hedgehog did
      not regulate cEbf1-3 expression in the PAs or associated ganglia. Bone
      morphogenetic protein 2 (Bmp2) can, however, directly and indirectly regulate
      cEbf1 and cEbf3 expression in the PAs and the proximal (NCC-derived) portion, but
      not the distal (placodal-derived) portion of the cranial sensory ganglia.
      Conversely, cEbf2 expression was upregulated following injection of Noggin before
      the migration of NCCs, but did not change after the overexpression of either
      Noggin or Bmp2 in the arch after NCC migration. In conclusion, Bmp2 regulates
      cEbf1 and cEbf3 expression in PAs and cranial sensory ganglia both directly and
      indirectly, via the migration of cranial NCCs. However, cEbf2 expression in the
      mesenchymal core of PAs is controlled by other undetermined signals.

PMID- 25613353
TI  - Photoreversible gelation of a triblock copolymer in an ionic liquid.
AB  - The reversible micellization and sol-gel transition of block copolymer solutions
      in an ionic liquid (IL) triggered by a photostimulus is described. The ABA
      triblock copolymer employed, denoted P(AzoMA-r-NIPAm)-b-PEO-b-P(AzoMA-r-NIPAm)),
      has a B block composed of an IL-soluble poly(ethylene oxide) (PEO). The A block
      consists of a random copolymer including thermosensitive N-isopropylacrylamide
      (NIPAm) units and a methacrylate with an azobenzene chromophore in the side chain
      (AzoMA). A phototriggered reversible unimer-to-micelle transition of a dilute ABA
      triblock copolymer (1 wt%) was observed in an IL, 1-butyl-3-methylimidazolium
      hexafluorophosphate ([C4mim]PF6), at an intermediate "bistable" temperature (50 
      degrees C). The system underwent a reversible sol-gel transition cycle at the
      bistable temperature (53  degrees C), with reversible association/fragmentation
      of the polymer network resulting from the phototriggered self-assembly of the ABA
      triblock copolymer (20 wt%) in [C4 mim]PF6.

PMID- 25613354
TI  - Boston heart surgeon shot and killed at Harvard teaching hospital.

PMID- 25613355
TI  - Falls and fallers in traumatic brain injury (TBI) rehabilitation settings: an
      integrative review.
AB  - PURPOSE: To critically appraise the research literature on the nature of falls
      and fallers in traumatic brain injury (TBI) rehabilitation settings. METHOD: An
      integrative review of the literature using thematic analysis was undertaken.
      Papers identified via a systematic search strategy were independently appraised
      by two reviewers. A data extraction instrument was developed to record results
      and to aid identification of themes in the literature. Critical Appraisal Skills
      Programme instruments were utilised to conduct a methodological critique of the
      papers included. RESULTS: Thirteen studies were identified as having between 4%
      and 100% TBI patients in their study cohorts. From these papers, up to 71% of
      falls took place in a patient's bedroom occurring in peaks and troughs over a 24
      h period. With some divergent results, nine themes were identified describing
      faller characteristics including: (1) functional mobility impairments; (2)
      dizziness; (3) bladder and bowel dysfunction; (4) certain medications and number
      of medications prescribed; (5) executive functioning; (6) patient age; (7) fear
      of falling; (8) coma length following TBI; and (9) Functional Independence
      Measure (FIMTM) total score, subscale scores and particular individual items.
      CONCLUSIONS: Being a multifactorial phenomenon, falls are a complex clinical
      issue. Despite the heterogeneity of diagnosis related groups (DRGs) in the
      included studies, TBI patients were identified as a high falls risk patient
      population in several studies. Implications for Rehabilitation Due to multisystem
      impairments, falls in the traumatic brain injury (TBI) rehabilitation context are
      a multifactorial and significant clinical issue. When interpreting and
      generalising results from research into falls, clinicians need to be mindful that
      falls and faller characteristics may be dependent on study setting and patient
      population. There is need for context specific research into faller
      characteristics following a TBI; particularly in relation to post-traumatic
      amnesia.

PMID- 25613356
TI  - Evaluation of various energy windows at different radionuclides for scatter and
      attenuation correction in nuclear medicine.
AB  - OBJECTIVE: Improving signal to noise ratio (SNR) and qualified images by the
      various methods is very important for detecting the abnormalities at the body
      organs. Scatter and attenuation of photons by the organs lead to errors in
      radiopharmaceutical estimation as well as degradation of images. The choice of
      suitable energy window and the radionuclide have a key role in nuclear medicine
      which appearing the lowest scatter fraction as well as having a nearly constant
      linear attenuation coefficient as a function of phantom thickness. METHODS: The
      energy windows of symmetrical window (SW), asymmetric window (ASW), high window
      (WH) and low window (WL) using Tc-99m and Sm-153 radionuclide with solid water
      slab phantom (RW3) and Teflon bone phantoms have been compared, and Matlab
      software and Monte Carlo N-Particle (MCNP4C) code were modified to simulate these
      methods and obtaining the amounts of FWHM and full width at tenth maximum (FWTM)
      using line spread functions (LSFs). The experimental data were obtained from the
      Orbiter Scintron gamma camera. RESULTS: Based on the results of the simulation as
      well as experimental work, the performance of WH and ASW display of the results,
      lowest scatter fraction as well as constant linear attenuation coefficient as a
      function of phantom thickness. WH and ASW were optimal windows in nuclear
      medicine imaging for Tc-99m in RW3 phantom and Sm-153 in Teflon bone phantom.
      Attenuation correction was done for WH and ASW optimal windows and for these
      radionuclides using filtered back projection algorithm. Results of simulation and
      experimental show that very good agreement between the set of experimental with
      simulation as well as theoretical values with simulation data were obtained which
      was nominally less than 7.07 % for Tc-99m and less than 8.00 % for Sm-153.
      Corrected counts were not affected by the thickness of scattering material. The
      Simulated results of Line Spread Function (LSF) for Sm-153 and Tc-99m in phantom
      based on four windows and TEW method were indicated that the FWHM and FWTM values
      were approximately the same in TEW method and WH and ASW, but the sensitivity at
      the optimal window was more than that of the other one. CONCLUSIONS: The suitable
      determination of energy window width on the energy spectra can be useful in
      optimal design to improve efficiency and contrast. It is found that the WH is
      preferred to the ASW and the ASW is preferred to the SW.

PMID- 25613358
TI  - Environmental releases from fuel cycle facility: part 1: radionuclide
      resuspension vs. stack releases on ambient airborne uranium and thorium levels.
AB  - Airborne activity levels of uranium and thorium series were measured in the
      vicinity (1.1 km) of a uranium (UF4) processing plant, located in Malvesi, south
      of France. Regarding its impact on the environment, this facility is
      characterized by its routine atmospheric releases of uranium and by the emission
      of radionuclide-labelled particles from a storage pond filled with waste water or
      that contain dried sludge characterized by traces of plutonium and thorium
      ((230)Th). This study was performed during a whole year (November 2009-November
      2010) and based on weekly aerosol sampling. Thanks to ICP-MS results, it was
      possible to perform investigations of uranium and thorium decay product
      concentration in the air. The number of aerosol filters sampled (50) was
      sufficient to establish a relationship between airborne radionuclide variations
      and the wind conditions. As expected, the more the time spent in the plume, the
      higher the ambient levels. The respective contributions of atmospheric releases
      and resuspension from local soil and waste ponds on ambient dust load and uranium
      bearing aerosols were estimated. Two shutdown periods dedicated to facility
      servicing made it possible to estimate the resuspension contribution and to
      specify its origin (local or regional) according to the wind direction and remote
      background concentration. Airborne uranium mainly comes from the emission stack
      and, to a minor extent (~20%), from wind resuspension of soil particles from the
      surrounding fields and areas devoted to waste storage. Moreover, weighed activity
      levels were clearly higher during operational periods than for shutdown periods.

PMID- 25613357
TI  - Discovery of highly potent tyrosinase inhibitor, T1, with significant anti
      melanogenesis ability by zebrafish in vivo assay and computational molecular
      modeling.
AB  - Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of
      melanin pigments leading to hyperpigmentation disorders that can be treated with
      depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated
      from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor
      against mushroom tyrosinase (IC50 = 0.53 MUM, Ki = 58 +/- 6 nM), outperforms than
      kojic acid. The cell viability and melanin quantification assay demonstrate that
      50 MUM of T1 apparently attenuates 20% melanin content of human normal
      melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo
      assay reveals that T1 effectively reduces melanogenesis with no adverse side
      effects. The acute oral toxicity study evidently confirms that T1 molecule is
      free of discernable cytotoxicity in mice. Furthermore, the molecular modeling
      demonstrates that the sulfur atom of T1 coordinating with the copper ions in the
      active site of tyrosinase is essential for mushroom tyrosinase inhibition and the
      ability of diminishing the human melanin synthesis. These results evident that T1
      isolated from Gastrodia elata is a promising candidate in developing
      pharmacological and cosmetic agents of great potency in skin-whitening. 

PMID- 25613359
TI  - Coagulation effect on the activity size distributions of long lived radon progeny
      aerosols and its application to atmospheric residence time estimation techniques.
AB  - The long lived naturally occurring radon progeny species in the atmosphere,
      namely (210)Pb, (210)Bi and (210)Po, have been used as important tracers for
      understanding the atmospheric mixing processes and estimating aerosol residence
      times. Several observations in the past have shown that the activity size
      distribution of these species peaks at larger particle sizes as compared to the
      short lived radon progeny species - an effect that has been attributed to the
      process of coagulation of the background aerosols to which they are attached. To
      address this issue, a mathematical equation is derived for the activity-size
      distribution of tracer species by formulating a generalized distribution function
      for the number of tracer atoms present in coagulating background particles in the
      presence of radioactive decay and removal. A set of these equations is
      numerically solved for the progeny chain using Fuchs coagulation kernel combined
      with a realistic steady-state aerosol size spectrum that includes nucleation,
      accumulation and coarse mode components. The important findings are: (i) larger
      shifts in the modal sizes of (210)Pb and (210)Po at higher aerosol concentrations
      such as that found in certain Asian urban regions (ii) enrichment of tracer
      specific activity on particles as compared to that predicted by pure attachment
      laws (iii) sharp decline of daughter-to-parent activity ratios for decreasing
      particle sizes. The implication of the results to size-fractionated residence
      time estimation techniques is highlighted. A coagulation corrected graphical
      approach is presented for estimating the residence times from the size-segregated
      activity ratios of (210)Bi and (210)Po with respect to (210)Pb. The discrepancy
      between the residence times predicted by conventional formula and the coagulation
      corrected approach for specified activity ratios increases at higher atmospheric
      aerosol number concentrations (>10(10) #/m(3)) for smaller sizes (<1 MUm). The
      results are further discussed.

PMID- 25613360
TI  - Tracheal intubation in an urban emergency department in Scotland: a prospective,
      observational study of 3738 intubations.
AB  - AIM: The emergency department (ED) is an area where major airway difficulties can
      occur, often as complications of rapid sequence induction (RSI). We undertook a
      prospective, observational study of tracheal intubation performed in a large,
      urban UK ED to study this further. METHODS: We reviewed data on every intubation
      attempt made in our ED between January 1999 and December 2011. We recorded
      techniques and drugs used, intubator details, success rate, and associated
      complications. Tracheal intubation in our ED is managed jointly by emergency
      physicians and anaesthetists; an anaesthetist is contacted to attend to support
      ED staff when RSI is being performed. RESULTS: We included 3738 intubations in
      analysis. 2749 (74%) were RSIs, 361 (10%) were other drug combinations, and 628
      (17%) received no drugs. Emergency physicians performed 78% and anaesthetists 22%
      of intubations. Tracheal intubation was successful in 3724 patients (99.6%).
      First time success rate was 85%; 98% of patients were successfully intubated with
      two or fewer attempts, and three patients (0.1%) had more than three attempts.
      Intubation failed in 14 patients; five (0.13%) had a surgical airway performed.
      Associated complications occurred in 286 (8%) patients. The incidence of
      complications was associated with the number of attempts made; 7% in one attempt,
      15% in two attempts, and 32% in three attempts (p<0.001). CONCLUSION: A
      collaborative approach between emergency physicians and anaesthetists contributed
      to a high rate of successful intubation and a low rate of complications. Close
      collaboration in training and delivery of service models is essential to maintain
      these high standards and achieve further improvement where possible.

PMID- 25613361
TI  - Life after cardiac arrest: A very long term follow up.
AB  - AIM: To describe survival and causes of death after cardiac arrest (CA) and the
      life situation of very long term survivors. METHODS: Individuals with successful
      resuscitation treated at the Sahlgrenska university hospital during 1995-1999 and
      presented in former CA publications were studied. Survival time and causes of
      death data were extracted from the individuals who had died's records. Very long
      term survivors were offered a follow up visit at home. Mini Mental State
      Examination (MMSE) used to describe cognitive abilities and EQ-5D to assess
      quality of life. The life situation was also explored. RESULTS: 14 out of 104
      possible participants had survived to follow up. The median time to follow up
      among the 8 who agreed to participation was 17 years. Out of the 8 participants,
      4 failed to reach the cut off score of normal cognitive abilities in the MMSE and
      7/8 participants did not reach the cut off score for normal cognitive function in
      the MoCA. Overall the participants were content with their life situation and
      QoL. However, a tendency towards lower scores on the cognitive testing and a
      lower self-reported QoL was observed. No depression, post-traumatic stress
      disorder or anxiety disorder were found. CONCLUSIONS: A CA may lead to permanent
      cognitive impairments and the risk of dementia may be higher because of the
      injuries sustained during the collapse. However, further studies with more
      participants are needed to fully determine the risk of cognitive impairment after
      a CA. Regarding life situation, there was a tendency of lower QoL with lower
      scores on the cognitive testing. With a new treatment paradigm, there is a need
      for long term studies regarding this new population.

PMID- 25613362
TI  - Sodium bicarbonate use during in-hospital pediatric pulseless cardiac arrest - a
      report from the American Heart Association Get With The Guidelines((r))
      Resuscitation.
AB  - BACKGROUND: Despite limited recommendations for using sodium bicarbonate (SB)
      during cardiopulmonary resuscitation (CPR), we hypothesized that SB continues to
      be used frequently during pediatric in-hospital cardiac arrest (IHCA) and that
      its use varies by hospital-specific, patient-specific, and event-specific
      characteristics. METHODS: We analyzed 3719 pediatric (<18 years) index pulseless
      CPR events from the American Heart Association Get With The Guidelines
      Resuscitation database from 1/2000 to 9/2010. RESULTS: SB was used in 2536 (68%)
      of 3719 CPR events. Incidence of SB use between 2000 and 2005 vs. 2006 and 2010
      was 71.1% vs. 66.2% (P=0.002). The primary outcome was survival to discharge.
      Secondary outcomes included 24-h survival and neurologic outcome. Multivariable
      logistic regression analyzed the association between SB use and outcomes. SB had
      increased use an ICU location, metabolic/electrolyte disturbance, prolonged CPR,
      pVT/VF, and concurrently with other pharmacologic interventions. Adjusting for
      confounding factors, SB use was associated with decreased 24-h survival (aOR
      0.83, 95% CI: 0.69, 0.99) and decreased survival to discharge (aOR 0.80; 95% CI:
      0.65, 0.97). Inclusion of metabolic/electrolyte abnormalities, hyperkalemia, and
      toxicologic abnormalities only (n=674), SB use was not associated with worse
      outcomes or unfavorable neurologic outcome. CONCLUSIONS: SB is used frequently
      during pediatric pulseless IHCA, yet there is a significant trend toward less
      routine use over the last decade. Because SB is more likely to be used in an ICU,
      with prolonged CPR, and concurrently with other pharmacologic interventions; its
      use during CPR may be associated with poor prognosis due to an association with
      "last ditch" efforts of resuscitation rather than causation.

PMID- 25613363
TI  - Assessing self-efficacy of frontline providers to perform newborn resuscitation
      in a low-resource setting.
AB  - OBJECTIVES: Newborn deaths comprise an alarming proportion of under-five
      mortality globally. In this retrospective cohort study, we investigated the
      effectiveness of focused newborn resuscitation training and delivery of a
      positive-pressure device in a rural midwife population in a low-resource setting.
      The present research attempts to better understand the extent to which knowledge
      and self-efficacy contribute to resuscitation attempts by birth attendants in
      practice. METHODS: A one-year retrospective cohort analysis was undertaken in
      Aceh, Indonesia of two groups of community-based midwives, one having received
      formal training and a positive-pressure resuscitative device and the other
      receiving usual educational resources and management. A path analysis was
      undertaken to evaluate relative determinants of actual resuscitation attempts.
      RESULTS: 348 community-based midwives participated in the evaluation and had
      attended 3116 births during the preceding year. Path analysis indicated that
      formal training in resuscitation and delivery of a positive-pressure device were
      significantly related to both increased knowledge (beta=0.55, p=0.001) and
      increased self-efficacy (beta=0.52, p=0.001) in performing neonatal
      resuscitations with a positive-pressure device. However, training impacted actual
      resuscitation attempts only indirectly through a relationship with self-efficacy
      and with knowledge. Combined across groups, self-efficacy was significantly
      associated with positive pressure ventilation attempts (beta=0.26, p<0.01)
      whereas knowledge was not (beta=-0.05, p=0.39). CONCLUSION: Although, to date,
      evaluations of newborn resuscitation programs have primarily focused on training
      and has reported process indicators, these results indicate that in order to
      improve intrapartum-related hypoxic events ("birth asphyxia"), increased emphasis
      should be placed on participant self-efficacy and mastery of newborn
      resuscitation.

PMID- 25613364
TI  - Profilin1 regulates invadopodium maturation in human breast cancer cells.
AB  - Invadopodia are actin-driven membrane protrusions that show oscillatory assembly
      and disassembly causing matrix degradation to support invasion and dissemination
      of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide
      binding protein, is downregulated in several adenocarcinomas and it is been shown
      that its depletion enhances invasiveness and motility of breast cancer cells by
      increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the
      first time that depletion of profilin1 leads to an increase in the number of
      mature invadopodia and these assemble and disassemble more rapidly than in
      control cells. Previous work by Sharma et al. (2013a), has shown that the binding
      of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium
      precursor causing it to mature into a degradation-competent structure. We found
      that loss of profilin1 expression increases the levels of PI(3,4)P2 at the
      invadopodium and as a result, enhances recruitment of the interacting adaptor
      Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of
      invadopodium anchorage, maturation, and turnover. Our results indicate that
      profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5
      recruitment in invadopodia to control the invasion efficiency of invadopodia. 

PMID- 25613365
TI  - Suppression of centrosome protein TACC3 induces G1 arrest and cell death through
      activation of p38-p53-p21 stress signaling pathway.
AB  - The centrosome regulates diverse cellular processes, including cell proliferation
      and differentiation. TACC3, a member of the human transforming acidic coiled-coil
      protein family, is a key centrosomal protein that is up-regulated in many
      cancers. Previous studies have demonstrated that TACC3 is essential for the
      survival of vertebrates and is involved in cell cycle regulation in human cells.
      However, the details of the underlying mechanisms in its cell cycle regulatory
      activity remain poorly understood. In this study, we showed that suppression of
      TACC3 expression induced G1 cell cycle arrest and triggered cell death in human
      cells. TACC3 depletion-induced G1 arrest and cell death were significantly
      reduced in cells either lacking p53 or with pharmacologically-inhibited p38,
      indicating that G1 arrest and cell death induction both require p53 and p38.
      TACC3 depletion up-regulated the levels of p53 and p21 and induced the
      accumulation of p53 both in the nucleus and at the centrosome. Interestingly,
      TACC3 depletion led to the activation of p38 and stimulated the recruitment of
      activated p38 to the centrosome. Depletion of TACC3 up-regulated the
      phosphorylation of p53 at Serine 33, a site known to be phosphorylated by p38
      under cellular stress and further induced the accumulation of phosphorylated p53
      to the centrosome. Loss of TACC3 affected centrosome integrity by disrupting the
      localization of components of the gamma-tubulin ring complex at the centrosome.
      The results demonstrate that TACC3 depletion induces G1 arrest and cell death by
      activating p38-p53-p21 signaling and triggering a centrosome-mediated cellular
      stress response. 

PMID- 25613366
TI  - Recent progress in theoretical and computational investigations of Li-ion battery
      materials and electrolytes.
AB  - There is an increasing worldwide demand for high energy density batteries. In
      recent years, rechargeable Li-ion batteries have become important power sources,
      and their performance gains are driving the adoption of electrical vehicles (EV)
      as viable alternatives to combustion engines. The exploration of new Li-ion
      battery materials is an important focus of materials scientists and computational
      physicists and chemists throughout the world. The practical applications of Li
      ion batteries and emerging alternatives may not be limited to portable electronic
      devices and circumventing hurdles that include range anxiety and safety among
      others, to their widespread adoption in EV applications in the future requires
      new electrode materials and a fuller understanding of how the materials and the
      electrolyte chemistries behave. Since this field is advancing rapidly and
      attracting an increasing number of researchers, it is crucial to summarise the
      current progress and the key scientific challenges related to Li-ion batteries
      from theoretical point of view. Computational prediction of ideal compounds is
      the focus of several large consortia, and a leading methodology in designing
      materials and electrolytes optimized for function, including those for Li-ion
      batteries. In this Perspective, we review the key aspects of Li-ion batteries
      from theoretical perspectives: the working principles of Li-ion batteries, the
      cathodes, anodes, and electrolyte solutions that are the current state of the
      art, and future research directions for advanced Li-ion batteries based on
      computational materials and electrolyte design. 

PMID- 25613367
TI  - Formation of DNA:RNA hybrid G-quadruplex in bacterial cells and its dominance
      over the intramolecular DNA G-quadruplex in mediating transcription termination.
AB  - DNA with four guanine tracts can fold into G-quadruplexes that are targets of
      transcription regulation. We recently found that hybrid DNA:RNA G-quadruplexes
      (HQs) can form during in vitro transcription. However, it is unclear whether they
      can form in cells. Evidence is presented supporting their formation in plasmids
      in bacterial cells. The formation of the HQs is indicated by a unique pattern of
      prematurely terminated transcripts under two conditions where the RNA transcripts
      do or do not participate in G-quadruplex assembly and further supported by a
      number of chemical and biochemical analysis. HQs dominate over the intramolecular
      DNA G-quadruplexes (DQ) in mediating the transcription termination when both
      structures are able to form. These findings provide the first evidence of HQ
      formation in cells and suggest that the competition/conversion between HQ and DQ
      may regulate transcription and serve as drug target in pharmaceutical
      applications. 

PMID- 25613368
TI  - Rates of breastfeeding and exposure to socio-economic adversity amongst children
      with intellectual disability.
AB  - Children with intellectual disability are at increased risk of experiencing poor
      health relative to their typically developing peers. Previous research indicates
      that exposure to socio-economic disadvantage contributes towards this disparity
      but that additional factors (including parenting practices) may be involved in
      mediating/moderating pathways. This study examined duration of breastfeeding
      amongst children with and without intellectual disability by a secondary analysis
      of data from the UK Millennium Cohort Study. Children with intellectual
      disability were significantly less likely to have been ever breastfed; breastfed
      exclusively or at all at 3 months or breastfed at all at 6 months relative to
      children without intellectual disability. None of these differences remained
      significant when other psycho-social risk factors for reduced breastfeeding were
      controlled for. The study adds to both the sparse literature on breastfeeding
      practices amongst families of children with intellectual disability and research
      demonstrating relationships between socio-economic disadvantage and wellbeing for
      children with intellectual disability. 

PMID- 25613369
TI  - Diagnostic Accuracy of Prenatal Ultrasound in Identifying Jejunal and Ileal
      Atresia.
AB  - INTRODUCTION: Small bowel atresia (SBA) is one of the most common causes of
      congenital intestinal obstruction. However, the accuracy of prenatal ultrasound
      in diagnosing this condition has not been entirely ascertained. The aim of this
      study was to analyse the predictive accuracy of ultrasound in detecting SBA
      prenatally. METHODOLOGY: Retrospective study of all cases with prenatal suspicion
      or postnatal confirmed SBA seen in a tertiary fetal medicine and pediatric
      surgery units from 2007 to 2013. Cases with duodenal atresia were excluded from
      the study. The predictive accuracy of ultrasound and different ultrasound signs,
      alone and in combination, was calculated. RESULTS: 65 fetuses with prenatal
      suspicion or postnatal confirmed SBA were enrolled. 58 cases had full data and
      were included in the analysis. Predictive accuracy of ultrasound in detecting the
      presence of SBA was poor, with a sensitivity of 50% (95% CI 26.0-74.0) and a
      specificity of 70.59% (95% CI 52.5-84.9). The presence of both bowel dilatation
      >=17 mm and polyhydramnios after 32 weeks of gestation slightly increased
      sensitivity (66.67%, 95% CI 34.9-90.1) and specificity (80.00%, 95% CI 44.4
      97.5). CONCLUSIONS: In case of suspicion of SBA before the 3rd trimester, an
      ultrasound after 32 weeks should be performed to confirm the presence of both
      polyhydramnios and bowel dilatation >17 mm.

PMID- 25613370
TI  - Identifying the unmet supportive care needs of men living with and beyond
      prostate cancer: A systematic review.
AB  - PURPOSE: Men affected by prostate cancer are a patient population in need of on
      going person-centred supportive care. Our aim was to synthesise current available
      evidence with regard to the unmet supportive care needs of men living with and
      beyond prostate cancer. METHODS: A systematic review was conducted according to
      the PRISMA Statement Guidelines. Electronic databases (DARE, Cochrane MEDLINE,
      BNI, PsychINFO, EMBASE and CIHAHL) were searched to identify studies employing
      qualitative and/or quantitative methods. Methodological evaluation was conducted,
      and findings were integrated in a narrative synthesis. RESULTS: 7521 references
      were retrieved, 17 articles met the eligibility criteria. Individual needs were
      classified into the following domains: social needs (2/17: 11.8%), spiritual
      needs (4/7: 23.5%), practical needs (4/17: 23.5%), daily living needs (5/17:
      29.4%), patient-clinician communication (5/17: 29.4%), family-related needs
      (7/17: 41.2%), physical needs (8/17: 47.1%), psychological emotional needs (9/17:
      52.9%), interpersonal/intimacy needs (11/17: 64.7%) and health system/Information
      needs (13/17: 76.5%). CONCLUSIONS: This systematic review has identified that men
      can experience a range of unmet supportive care needs with the most frequently
      reported being needs related to intimacy, informational, physical and
      psychological needs. Despite the emerging evidence-base, the current with-in
      study limitations precludes our understanding about how the needs of men evolve
      over time from diagnosis to living with and beyond prostate cancer. Whether
      demographic or clinical variables play a moderating role, only remains to be
      addressed in future studies. This review has made an important contribution by
      informing clinicians about the complex unmet supportive care needs of men
      affected by this disease.

PMID- 25613371
TI  - Measurement reliability and effect direction for self-efficacy and pain in
      colorectal cancer patients.

PMID- 25613372
TI  - Anti-mycobacterial peptides: from human to phage.
AB  - Mycobacterium tuberculosis is the major pathogen of tuberculosis (TB). With the
      growing problem of M. tuberculosis resistant to conventional antibiotics,
      especially multi-drug resistant tuberculosis (MDR-TB) and extensively-drug
      resistant tuberculosis (XDR-TB), the need for new TB drugs is now more prominent
      than ever. Among the promising candidates for anti-TB drugs, anti-mycobacterial
      peptides have a few advantages, such as low immunogenicity, selective affinity to
      prokaryotic negatively charged cell envelopes, and diverse modes of action. In
      this review, we summarize the recent progress in the anti-mycobacterial peptides,
      highlighting the sources, effectiveness and bactericidal mechanisms of these
      antimicrobial peptides. Most of the current anti-mycobacterial peptides are
      derived either from host immune cells, bacterial extraction, or
      mycobacteriophages. Besides trans-membrane pore formation, which is considered to
      be the common bactericidal mechanism, many of the anti-mycobacterial peptides
      have the second non-membrane targets within mycobacteria. Additionally, some
      antimicrobial peptides play critical roles in innate immunity. However, a few
      obstacles, such as short half-life in vivo and resistance to antimicrobial
      peptides, need overcoming before clinical applications. Nevertheless, the
      multiple functions of anti-mycobacterial peptides, especially direct killing of
      pathogens and immune-modulators in infectious and inflammatory conditions,
      indicate that they are promising candidates for future drug development.

PMID- 25613374
TI  - Necroptosis suppresses inflammation via termination of TNF- or LPS-induced
      cytokine and chemokine production.
AB  - TNF promotes a regulated form of necrosis, called necroptosis, upon inhibition of
      caspase activity in cells expressing RIPK3. Because necrosis is generally more
      pro-inflammatory than apoptosis, it is widely presumed that TNF-induced
      necroptosis may be detrimental in vivo due to excessive inflammation. However,
      because TNF is intrinsically highly pro-inflammatory, due to its ability to
      trigger the production of multiple cytokines and chemokines, rapid cell death via
      necroptosis may blunt rather than enhance TNF-induced inflammation. Here we show
      that TNF-induced necroptosis potently suppressed the production of multiple TNF
      induced pro-inflammatory factors due to RIPK3-dependent cell death. Similarly,
      necroptosis also suppressed LPS-induced pro-inflammatory cytokine production.
      Consistent with these observations, supernatants from TNF-stimulated cells were
      more pro-inflammatory than those from TNF-induced necroptotic cells in vivo. Thus
      necroptosis attenuates TNF- and LPS-driven inflammation, which may benefit
      intracellular pathogens that evoke this mode of cell death by suppressing host
      immune responses. 

PMID- 25613373
TI  - A RING to rule them all? Insights into the Map3k1 PHD motif provide a new
      mechanistic understanding into the diverse roles of Map3k1.
AB  - Despite the sizable number of components that comprise Mapk cascades, Map3k1 is
      the only element that contains both a kinase domain and a plant homeodomain (PHD)
      motif, allowing Map3k1 to regulate the protein phosphorylation and ubiquitin
      proteasome systems. As such, Map3k1 has complex roles in the regulation of cell
      death, survival, migration and differentiation. Numerous mouse and human genetic
      analyses have demonstrated that Map3k1 is of critical importance for the immune
      system, cardiac tissue, testis, wound healing, tumorigenesis and cancer. Recent
      gene knockin of Map3k1 to mutate the E2 binding site within the Map3k1 PHD motif
      and high throughput ubiquitin protein array screening for Map3k1 PHD motif
      substrates provide critical novel insights into Map3k1 PHD motif signal
      transduction and bring a brand-new understanding to Map3k1 signaling in mammalian
      biology. 

PMID- 25613375
TI  - USP11-dependent selective cIAP2 deubiquitylation and stabilization determine
      sensitivity to Smac mimetics.
AB  - Given their crucial role in apoptosis suppression, inhibitor of apoptosis
      proteins (IAPs) have recently become attractive targets for cancer therapy. Here,
      we report that cellular IAP2 (cIAP2) is specifically stabilized in several cancer
      cell lines, leading to resistance to Smac mimetics, such as BV6 and birinapant.
      In particular, our results showed that cIAP2 depletion, but not cIAP1 depletion,
      sensitized cancer cells to Smac mimetic-induced apoptosis. Ubiquitin-specific
      protease 11 (USP11) is a deubiquitylase that directly stabilizes cIAP2. USP11
      overexpression is frequently found in colorectal cancer and melanoma and is
      correlated with poor survival. In our study, cancer cell lines expressing high
      levels of USP11 exhibited strong resistance to Smac mimetic-induced cIAP2
      degradation. Furthermore, USP11 downregulation sensitized these cells to
      apoptosis induced by TRAIL and BV6 and suppressed tumor growth in a xenograft
      model. Finally, the TNFalpha/JNK pathway induced USP11 expression and maintained
      cIAP2 stability, suggesting an alternative TNFalpha-dependent cell survival
      pathway. Collectively, our data suggest that USP11-stabilized cIAP2 may serve as
      a barrier against IAP-targeted clinical approaches.

PMID- 25613376
TI  - TSPYL2 is an essential component of the REST/NRSF transcriptional complex for
      TGFbeta signaling activation.
AB  - REST/NRSF is a transcriptional repressor of neuronal genes that has been
      implicated in development and cancer. In epithelial tissues, REST acts as a tumor
      suppressor and in breast cancer, loss of REST is associated with disease
      recurrence and poor prognosis. Here, we identify TSPYL2 (also known as CDA1 and
      DENTT) as a novel component of the REST protein complex. We show that REST and
      TSPYL2 are regulators of TGFbeta signaling and that cell-cycle arrest induced by
      TGFbeta requires both REST and TSPYL2. Importantly, knockdown of REST or TSPYL2
      resulted in transformation of human mammary epithelial cells. Mechanistically, we
      demonstrate that the TSPYL2/REST complex promotes TGFbeta signaling by repressing
      the expression of genes, such as the proto-oncogene neurotrophic tyrosine kinase
      receptor C (TrkC). These data provide insight into the role of REST as a tumor
      suppressor in epithelial tissues through the regulation of the TGFbeta pathway. 

PMID- 25613377
TI  - CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma.
AB  - Cancer stem cells (CSCs) have been implicated in the initiation and maintenance
      of tumour growth as well as metastasis. Recent reports link stemness to
      epithelial-mesenchymal transition (EMT) in cancer. However, there is still little
      knowledge about the molecular markers of those events. In silico analysis of RNA
      profiles of 36 pancreatic ductal adenocarcinomas (PDAC) reveals an association of
      the expression of CD95 with EMT and stemness that was validated in CSCs isolated
      from PDAC surgical specimens. CD95 expression was also higher in metastatic
      pancreatic cells than in primary PDAC. Pharmacological inhibition of CD95
      activity reduced PDAC growth and metastasis in CSC-derived xenografts and in a
      murine syngeneic model. On the mechanistic level, Sck was identified as a novel
      molecule indispensable for CD95's induction of cell cycle progression. This study
      uncovers CD95 as a marker of EMT and stemness in PDAC. It also addresses the
      molecular mechanism by which CD95 drives tumour growth and opens tantalizing
      therapeutic possibilities in PDAC. 

PMID- 25613378
TI  - Mitochondrial ATP transporter Ant2 depletion impairs erythropoiesis and B
      lymphopoiesis.
AB  - Adenine nucleotide translocases (ANTs) transport ADP and ATP through
      mitochondrial inner membrane, thus playing an essential role for energy
      metabolism of eukaryotic cells. Mice have three ANT paralogs, Ant1 (Slc25a4),
      Ant2 (Slc25a5) and Ant4 (Slc25a31), which are expressed in a tissue-dependent
      manner. While knockout mice have been characterized with Ant1 and Ant4 genes,
      which resulted in exercise intolerance and male infertility, respectively, the
      role of the ubiquitously expressed Ant2 gene in animal development has not been
      fully demonstrated. Here, we generated Ant2 hypomorphic mice by targeted
      disruption of the gene, in which Ant2 expression is largely depleted. The mice
      showed apparently normal embryonic development except pale phenotype along with a
      reduced birth rate. However, postnatal growth was severely retarded with
      macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, and
      died within 4 weeks. Ant2 depletion caused anemia in a cell-autonomous manner by
      maturation arrest of erythroid precursors with increased reactive oxygen species
      and premature deaths. B-lymphocyte development was similarly affected by Ant2
      depletion, and splenocytes showed a reduction in maximal respiration capacity and
      cellular ATP levels as well as an increase in cell death accompanying
      mitochondrial permeability transition pore opening. In contrast, myeloid,
      megakaryocyte and T-lymphocyte lineages remained apparently intact. Erythroid and
      B-cell development may be particularly vulnerable to Ant2 depletion-mediated
      mitochondrial dysfunction and oxidative stress. 

PMID- 25613380
TI  - eIF4A1 is a promising new therapeutic target in ER-negative breast cancer.

PMID- 25613379
TI  - Apoptotic mechanisms during competition of ribosomal protein mutant cells: roles
      of the initiator caspases Dronc and Dream/Strica.
AB  - Heterozygosity for mutations in ribosomal protein genes frequently leads to a
      dominant phenotype of retarded growth and small adult bristles in Drosophila (the
      Minute phenotype). Cells with Minute genotypes are subject to cell competition,
      characterized by their selective apoptosis and removal in mosaic tissues that
      contain wild-type cells. Competitive apoptosis was found to depend on the pro
      apoptotic reaper, grim and head involution defective genes but was independent of
      p53. Rp/+ cells are protected by anti-apoptotic baculovirus p35 expression but
      lacked the usual hallmarks of 'undead' cells. They lacked Dronc activity, and
      neither expression of dominant-negative Dronc nor dronc knockdown by dsRNA
      prevented competitive apoptosis, which also continued in dronc null mutant cells
      or in the absence of the initiator caspases dredd and dream/strica. Only
      simultaneous knockdown of dronc and dream/strica by dsRNA was sufficient to
      protect Rp/+ cells from competition. By contrast, Rp/Rp cells were also protected
      by baculovirus p35, but Rp/Rp death was dronc-dependent, and undead Rp/Rp cells
      exhibited typical dronc-dependent expression of Wingless. Independence of p53 and
      unusual dependence on Dream/Strica distinguish competitive cell death from
      noncompetitive apoptosis of Rp/Rp cells and from many other examples of cell
      death. 

PMID- 25613382
TI  - Ketamine treatment partly reverses alterations in brain derived- neurotrophic
      factor, oxidative stress and energy metabolism parameters induced by an animal
      model of depression.
AB  - Studies have suggested that ketamine, a nonselective NMDA receptor antagonist,
      could be a new drug in the treatment of major depression, but the way ketamine
      presents such effects remains to be elucidated. Therefore, the objective of this
      paper was to evaluate the effects of ketamine treatment on parameters related to
      depression in the brain of adult rats subjected to an animal model of depression.
      The animals were divided into: non-deprived + saline; non-deprived + ketamine;
      deprived + saline; deprived + ketamine. Treatments involving ketamine (15 mg/kg)
      were administered once a day during 14 days in the animal's adult phase. After
      treatment, the brain derived-neurotrophic factor (BDNF) levels, oxidative stress
      and energy metabolism activity were evaluated in brain structures of rats
      involved in the circuit of depression. In the amygdala, hippocampus and nucleus
      accumbens (NAc), a reduction in BDNF levels was observed in deprived rats, but
      the animals treated with ketamine reversed the effects of this animal model only
      in the amygdala and NAc. In addition to this, the complex I activity, in deprived
      rats, was diminished in the prefrontal cortex (PFC) and amygdala; in the PFC and
      hippocampus, the complex II-III was diminished in deprived rats; still the
      administration of ketamine increased the complex IV activity in the PFC and
      amygdala of rats submitted to the maternal deprivation. In deprived rats, the
      creatine kinase activity was reduced in the PFC and amygdala, however the
      administration of ketamine reversed this decrease in the amygdala. The
      malondialdehyde (MDA) equivalents were increased in non-deprived rats treated
      with ketamine in the PFC and NAc. Carbonyl levels in the PFC were diminished in
      control rats that received saline. Though ketamine treatment reversed this effect
      in deprived rats in the PFC and hippocampus. Still, in NAc, the carbonyl levels
      were diminished in deprived rats. The superoxide dismutase (SOD) activity was
      increased in control rats that received ketamine in the PFC and NAc, and were
      diminished in deprived rats that received saline or ketamine in the PFC and
      hippocampus. These findings may help to explain that dysfunctions involving BDNF,
      oxidative stress and energy metabolism within specific brain areas, may be linked
      with the pathophysiology of depression, and antidepressant effects of ketamine
      can be positive, at least partially due to the control of these pathways. 

PMID- 25613381
TI  - Interplay of H2A deubiquitinase 2A-DUB/Mysm1 and the p19(ARF)/p53 axis in
      hematopoiesis, early T-cell development and tissue differentiation.
AB  - Monoubiquitination of core histone 2A (H2A-K119u) has a critical role in gene
      regulation in hematopoietic differentiation and other developmental processes. To
      explore the interplay of histone H2A deubiquitinase Myb-like SWIRM and MPN domain
      containing1 (2A-DUB/Mysm1) with the p53 axis in the sequential differentiation of
      mature lymphocytes from progenitors, we systematically analyzed hematopoiesis and
      early T-cell development using Mysm1(-/-) and p53(-/-)Mysm1(-/-) mice. Mysm1(-/-)
      thymi were severely hypoplastic with <10% of wild-type cell numbers as a result
      of a reduction of early thymocyte progenitors in context with defective
      hematopoietic stem cells, a partial block at the double-negative (DN)1-DN2
      transition and increased apoptosis of double-positive thymocytes. Increased rates
      of apoptosis were also detected in other tissues affected by Mysm1 deficiency,
      including the developing brain and the skin. By quantitative PCR and chromatin
      immunoprecipitation analyses, we identified p19(ARF), an important regulator of
      p53 tumor suppressor protein levels, as a potential Mysm1 target gene. In newly
      generated p53(-/-)Mysm1(-/-) double-deficient mice, anomalies of Mysm1(-/-) mice
      including reduction of lymphoid-primed multipotent progenitors, reduced thymocyte
      numbers and viability, and interestingly defective B-cell development, growth
      retardation, neurological defects, skin atrophy, and tail malformation were
      almost completely restored as well, substantiating the involvement of the p53
      pathway in the alterations caused by Mysm1 deficiency. In conclusion, this
      investigation uncovers a novel link between H2A deubiquitinase 2A-DUB/Mysm1 and
      suppression of p53-mediated apoptotic programs during early lymphoid development
      and other developmental processes. 

PMID- 25613383
TI  - Prenatal indices for mandibular retrognathia/micrognathia.
AB  - OBJECTIVE: Micro- and retrognathia of mandibular origin may lead to life
      threatening respiratory problems in connection with glossoptosis immediately
      after birth. Prenatal screening for this malformation is therefore increasingly
      important. Today this is accomplished by predominantly subjective standards.
      Objective criteria have been proposed but have not become established. We
      therefore made an effort to develop indices that would identify major skeletal
      discrepancies or micrognathia in as straightforward a fashion as possible during
      routine prenatal sonography. MATERIALS AND METHODS: Series of fetal jaw sonograms
      (Toshiba Aplio MX(r)) were obtained in 313 women with normal pregnancies from
      weeks 19-29 of gestation. Upper- and lower-jaw landmarks were interactively
      located on screen and evaluated for reproducibility. Linear parameters
      representative of maxillary and mandibular length (SpA'-SpP' and Rami-SymMe) were
      measured and related to femur length and gestational age. Based on these data,
      indices for maxillary, and mandibular length were derived and analyzed. RESULTS:
      High correlations were identified for mandibular length both with gestational age
      (R = 0.845; R(2) = 0.713) and with femur length (correlation coefficients (R) =
      0.839; coefficients of determination (R(2)) = 0.704). For maxillary length, the
      respective correlation coefficients were 0.691 (R(2) = 0.477) and 0.656 (R(2) =
      0.430). Estimates of mandibular and maxillary length based on gestational age and
      femur length were obtained by regression analysis. The mean bimaxillary length
      ratio was 0.628 +/- 0.043. CONCLUSION: Maxillary and mandibular growth can be
      objectively evaluated via indices. It is conceivable to develop this approach
      into a sensitive and reliable method of prenatal jaw screening for major skeletal
      anomalies and congenital malformations.

PMID- 25613384
TI  - Effects of varying mandibular protrusion and degrees of vertical opening on upper
      airway dimensions in apneic dentate subjects.
AB  - INTRODUCTION: Despite numerous studies investigating the dimensional and
      therapeutic effects of mandibular advancement splints (MASs), data regarding the
      effects of differently designed individual and non-adjustable MASs on the upper
      airway in fully dentate apneic subjects in the sagittal plane including
      comparison of these effects with a placebo device are sparse. The present study
      aimed to determine the dimensional changes in the sagittal plane created by
      differently designed MASs in the upper airway in fully dentate apneic subjects
      and to compare these changes with the effects of a placebo device. MATERIALS AND
      METHODS: Magnetic resonance (MR) images of 9 dentate apneic subjects with 5
      differently designed MASs and without a MAS were obtained. We measured the area
      of the entire pharynx (velopharynx, oropharynx, hypopharynx) on these MR images
      and compared the dimensional changes. RESULTS: The dimensional changes triggered
      by two specific MASs (75% of the maximum mandibular protrusion with 5 mm vertical
      opening, and 75% of the maximum mandibular protrusion with 10 mm of vertical
      opening) in the entire pharynx in the sagittal plane were statistically
      significant compared to the other MASs (p < 0.05). The MAS effecting 75% of the
      maximum mandibular protrusion and 10 mm of vertical opening created a significant
      dimensional increase only in the velopharyngeal area among the three pharyngeal
      sites (p <= 0.003). CONCLUSION: While the degree of mandibular protrusion created
      by the MAS affects the dimensions of the upper airway, the degree of the vertical
      opening exerts no significant dimensional effect in the sagittal plane in fully
      dentate apneic patients. The mandibular protrusion effect is comparatively larger
      in the velopharyngeal region.

PMID- 25613385
TI  - A longitudinal study of dental arches and occlusal changes in adults from 22 to
      33, and 33 to 43 years of age.
AB  - The purpose of the present study was to conduct a longitudinal examination of
      changes in width, depth, anterior space, overjet, and overbite in the dental arch
      in men and women from 22 (T1) to 43 (T3) years of age and to explore any
      differences between the age periods 22-33 (T1-T2) and 33-43 (T2-T3) years as well
      as gender differences at T1 and changes within the two periods. The research
      material consisted of models of 32 men and 33 women. The parameters were measured
      with an electronic caliper. Repeated measurements of 20 pairs of randomly
      selected models were taken to check the reliability of our results. A significant
      decrease in intercuspid width, arch depth, and anterior space was observed in
      both arches of both genders. The changes were generally greater during the first
      observation period, and there were no significant gender difference. At T1 the
      men's arches were larger than those of the women.

PMID- 25613386
TI  - Letter to the editor: Popovic N, Drinkuth N, Toll DE (2014) Prevalence of class
      III malocclusion and crossbite among children and adolescents with
      craniomandibular dysfunction. (Pravalenz der Klasse-III-Malokklusion und des
      Kreuzbisses bei Kindern und Jugendlichen mit kraniomandibularer Dysfunktion.) J
      Orofac Orthop 74:36-41.

PMID- 25613387
TI  - Interaction association analysis of imputed SNPs in case-control and follow-up
      studies.
AB  - A new method is described to assess the interactions of imputed SNPs (single
      nucleotide polymorphisms) in case-control and follow-up studies, properly
      incorporating SNP imputation uncertainty in the likelihood model. Using
      simulation studies and analysis of real data obtained from the Framingham study
      cohort, we compare the performance of this new method to DOSAGE and NAIVE (also
      known as Best-Guess) methods, developed and commonly used in the context of
      single SNP and extended to SNP-by-SNP interaction. The results show that only our
      new method is unbiased under all examined scenarios regarding allele frequencies,
      imputation uncertainty degree, and interaction effect size. In addition, our
      method achieves at least as much power as the other two, and exceeds their
      statistical power in certain follow-up analysis situations. This method is fast
      enough to perform Genome Wide Interaction Studies (GWIS) with hundreds of
      thousands of interactions. By performing an exhaustive simulation study let us to
      provide recommendations for selecting the most appropriated method depending on
      MAF, interaction effect size, and uncertainty degree. In general, DOSAGE and our
      proposed method are recommended in most situations being our method more powerful
      and accurate when uncertainty and effect increase. 

PMID- 25613388
TI  - Extracapsular Extension of Pelvic Lymph Node Metastasis is an Independent
      Prognostic Factor in Bladder Cancer: A Systematic Review and Meta-analysis.
AB  - PURPOSE: We aimed to elucidate the relation between extracapsular extension (ECE)
      and clinical outcomes in node-positive patients following radical cystectomy for
      bladder cancer. METHODS: Following the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines, we searched PubMed, SCOPUS, Web of Science,
      and Cochrane Library databases from their respective dates of inception until
      September 2014. RESULTS: Ten articles that met the eligibility criteria included
      43-748 subjects per study, with the total number of patients being 1,893. The
      frequency of ECE ranged from 36.6 to 58.1 %. The pooled hazard ratio (HR) was
      statistically significant for recurrence-free survival (RFS) [pooled HR 1.56; 95
      % confidence interval (CI) 1.13-2.14] and cancer-specific survival (CSS) (pooled
      HR 1.60; 95 % CI 1.29-1.99) but not overall survival (OS) (pooled HR 1.47; 95 %
      CI 0.71-3.05). Heterogeneity in RFS (I (2) 84 %, p < 0.00001) and OS (I (2) 80 %,
      p = 0.03) was statistically significant. According to subgroup analysis with meta
      regression analyses, "region" (pheterogeneity < 0.0001) and "analysis results"
      (pheterogeneity < 0.0001) were the sources of heterogeneity. Sensitivity analysis
      showed that omission of any study did not lead to a significant difference. No
      statistical evidence of publication bias regarding RFS or CSS was revealed among
      the studies using Begg's and Egger's tests. CONCLUSIONS: This meta-analysis shows
      that ECE is an efficient prognostic factor for node-positive bladder cancer.
      However, large prospective studies are needed to confirm the clinical utility of
      ECE as an independent prognostic factor before these results can be applied
      clinically.

PMID- 25613389
TI  - Oncological outcomes of nerve-sparing radical hysterectomy for cervical cancer: a
      systematic review.
AB  - BACKGROUND: This study aimed to review the oncologic outcomes of nerve-sparing
      radical hysterectomy (NSRH) in cervical cancer and to compare them with those of
      standard conventional radical hysterectomy (CRH). METHODS: A search of the
      MEDLINE (Ovid), EMBASE (Ovid), and Cochrane Central Register of Controlled Trials
      (CENTRAL) databases for studies published to March 3, 2014 was performed using
      the search term "nerve sparing or radical hysterectomy and cervical cancer." The
      main outcome measure was the recurrence rate after NSRH. The hazard ratio for
      recurrence was used to compare NSRH and CRH. RESULTS: A total of 21 studies
      reported data on oncologic outcomes of NSRH. The recurrence rate after NSRH was
      reported to be 0 to 19.6 %. Of the 21 studies, 10 comparing outcomes between NSRH
      and CRH were assessed for their eligibility to be included in a meta-analysis.
      However, the scarcity and heterogeneity of effect estimates in these comparison
      trials precluded performance of a meta-analysis. CONCLUSIONS: The results showed
      that the evidence addressing the oncologic safety of NSRH over that of CRH in
      cervical cancer is neither adequate nor statistically relevant. A properly
      designed, prospective randomized noninferiority trial is needed to assess the
      oncologic outcomes of NSRH before this surgical approach is adopted as the
      standard of care for patients with tumors that have unfavorable prognostic
      features. Until then, NSRH should be considered primarily for patients with small
      tumors due to the very low risk of parametrial and lymph node involvement, with
      maximum benefit conferred to the patient from autonomic nerve preservation
      without any requirement for adjuvant treatment.

PMID- 25613390
TI  - The H3K9 Methyltransferase G9a Represses E-cadherin and is Associated with
      Myometrial Invasion in Endometrial Cancer.
AB  - BACKGROUND: Emerging evidence suggests that G9a, a histone methyltransferase, is
      involved in tumor progression and metastasis. However, the functional
      significance of G9a in endometrial carcinogenesis has not been defined. METHODS:
      The differential expression of G9a in cancer and normal tissues was assessed
      using an array of 28 paired samples. Tissue specimens from 94 patients with
      endometrial cancer who underwent primary surgery were immunohistochemically
      evaluated for G9a and E-cadherin expression. To assess the biologic role of G9a
      in endometrial cancer, G9a was either stably knocked down or knocked down using a
      tetracycline-controllable system in endometrial cancer cells, followed by
      functional assays. RESULTS: Increased G9a expression was identified in
      endometrial cancer tissues, and its expression was specifically correlated with
      deep myometrial invasion. Cell invasiveness was inhibited by an RNAi-mediated
      knockdown of G9a in invasive endometrial cancer cells in vitro and in vivo. An
      important mediator of G9a-induced tumor invasion is the epigenetic silencing of E
      cadherin. Knockdown of G9a restored E-cadherin expression by reducing H3K9me2
      levels and decreasing CDH1 promoter DNA methyltransferase recruitment. Knockdown
      of RNAi-mediated E-cadherin substantially relieved the invasion suppression
      imposed by G9a suppression. A significant negative correlation between G9a and E
      cadherin expression was observed in endometrial cancer (Spearman's rho, -0.27; P
      = 0.02). CONCLUSIONS: This study provides the first clear evidence that G9a
      contributes to endometrial cancer progression. Mechanistic investigations suggest
      that E-cadherin repression mediates the effects of G9a. Targeting G9a-mediated
      epigenetic pathway dysregulation may be a therapeutic strategy for endometrial
      cancers.

PMID- 25613391
TI  - Impacts of low coverage depths and post-mortem DNA damage on variant calling: a
      simulation study.
AB  - BACKGROUND: Massively parallel sequencing platforms, featuring high throughput
      and relatively short read lengths, are well suited to ancient DNA (aDNA) studies.
      Variant identification from short-read alignment could be hindered, however, by
      low DNA concentrations common to historic samples, which constrain sequencing
      depths, and post-mortem DNA damage patterns. RESULTS: We simulated pairs of
      sequences to act as reference and sample genomes at varied GC contents and
      divergence levels. Short-read sequence pools were generated from sample
      sequences, and subjected to varying levels of "post-mortem" damage by adjusting
      levels of fragmentation and fragmentation biases, transition rates at sequence
      ends, and sequencing depths. Mapping of sample read pools to reference sequences
      revealed several trends, including decreased alignment success with increased
      read length and decreased variant recovery with increased divergence. Variants
      were generally called with high accuracy, however identification of SNPs (single
      nucleotide polymorphisms) was less accurate for high damage/low divergence
      samples. Modest increases in sequencing depth resulted in rapid gains in total
      variant recovery, and limited improvements to recovery of heterozygous variants.
      CONCLUSIONS: This in silico study suggests aDNA-associated damage patterns
      minimally impact variant call accuracy and recovery from short-read alignment,
      while modest increases in sequencing depth can greatly improve variant recovery.

PMID- 25613392
TI  - Unplanned resection of a soft tissue sarcoma: clinical characteristics and impact
      on oncological and functional outcomes.
AB  - BACKGROUND: Over the past three decades, several studies have reported worse
      outcomes with unplanned resection for malignant soft tissue tumors. However, the
      impact of these studies on preventing unnecessary unplanned resection remains
      unknown. METHODS: In a retrospective survey on the treatment of soft tissue
      sarcomas, we compared cases of unplanned resection with cases of planned
      resection in terms of the properties of unplanned resection and the oncological
      and functional outcomes. For the unplanned resection cases, an additional wide
      resection was performed. RESULTS: Of 92 cases, unplanned resection was performed
      in 24 (26 %). Small or subcutaneous tumors were significantly more frequently
      subjected to unplanned resection. In 17 of 24 unplanned resection cases, residual
      tumors (70.8 %) were noted. Plastic surgery was more frequently needed for
      unplanned resection cases. There was no significant difference between the
      unplanned resection and control cases with regard to oncological outcome.
      However, as to local recurrence and overall survival, the events occurred only in
      the cases with residual tumors in the additional wide resection specimen in the
      unplanned resection group. There was no significant difference in functional
      evaluation, except for emotional acceptance, which had a better score in the
      unplanned resection group. CONCLUSIONS: Despite repeated cautions regarding
      unplanned resection in terms of its inadequate procedure which contradicts the
      principles of soft tissue sarcoma treatment, unplanned resections are still
      frequently performed. Perhaps the small size and subcutaneous location of the
      sarcomas in the unplanned resection group did not evoke the probability of
      malignancy for the surgeons who initially managed them. Even though an additional
      wide resection was performed, a residual tumor would lead to a worse outcome. An
      effective awareness program to avoid unnecessary unplanned resections for soft
      tissue sarcoma should be considered.

PMID- 25613393
TI  - Monitoring of blood pressure during total hip arthroplasty using the interface
      bioactive bone cement (IBBC) technique.
AB  - BACKGROUND: Cement implantation syndrome, which is characterized by hypotension,
      hypoxemia, and cardiac arrhythmia or arrest, has been reported in the literature.
      The purpose of the present study was to monitor the blood pressure changes that
      occur after cementing during primary total hip arthroplasty (THA). METHODS: The
      present study examined 178 cases in which 204 joints were treated with primary
      THA. Study subjects had a mean age at the time of surgery of 64.5 years (range 35
      89). Under general anesthesia, both hip components were cemented in place using
      an anterolateral approach. After cementing, systolic arterial blood pressure was
      measured at 1-min intervals for 5 min and then again at 10 min. The maximum
      regulation ratio (MRR) was calculated as follows: (maximum change in blood
      pressure - blood pressure before cement application) divided by blood pressure
      before cement application. RESULTS: No major complications, such as cardiac
      arrest, occurred in most cases; blood pressure increased until 4 mins on the
      acetabular side and until 2 min on the femoral side, and then gradually returned
      to the level observed prior to cement application. On the acetabular side, the
      mean MRR was 11.2 % [standard deviation (SD): 15.9; range -26 to -80], whereas it
      was 6.4 % (SD: 14.9; range -31 to -65) on the femoral side. Correlations were
      detected between MRR classification on the acetabular side and the subject's age
      at the time of the operation or bleeding control status on the acetabular side.
      When bleeding control was judged as complete, the tendency for blood pressure to
      decrease was reduced. Conversely, when bleeding control was judged as good, blood
      pressure showed a greater tendency to decrease. CONCLUSION: In the present study,
      no episodes of major hypotension occurred. During THA involving the interface
      bioactive bone cement (IBBC) technique, when bleeding control on the acetabular
      side was judged as complete the tendency for blood pressure to decrease was
      reduced.

PMID- 25613394
TI  - Crucial role of the Rap G protein signal in Notch activation and leukemogenicity
      of T-cell acute lymphoblastic leukemia.
AB  - The Rap G protein signal regulates Notch activation in early thymic progenitor
      cells, and deregulated Rap activation (Rap(high)) results in the development of
      Notch-dependent T-cell acute lymphoblastic leukemia (T-ALL). We demonstrate that
      the Rap signal is required for the proliferation and leukemogenesis of
      established Notch-dependent T-ALL cell lines. Attenuation of the Rap signal by
      the expression of a dominant-negative Rap1A17 or Rap1GAP, Sipa1, in a T-ALL cell
      line resulted in the reduced Notch processing at site 2 due to impaired
      maturation of Adam10. Inhibition of the Rap1 prenylation with a geranylgeranyl
      transferase inhibitor abrogated its membrane-anchoring to Golgi-network and
      caused reduced proprotein convertase activity required for Adam10 maturation.
      Exogenous expression of a mature form of Adam10 overcame the Sipa1-induced
      inhibition of T-ALL cell proliferation. T-ALL cell lines expressed Notch ligands
      in a Notch-signal dependent manner, which contributed to the cell-autonomous
      Notch activation. Although the initial thymic blast cells barely expressed Notch
      ligands during the T-ALL development from Rap(high) hematopoietic progenitors in
      vivo, the ligands were clearly expressed in the T-ALL cells invading extrathymic
      vital organs. These results reveal a crucial role of the Rap signal in the Notch
      dependent T-ALL development and the progression. 

PMID- 25613395
TI  - Reirradiation of locally recurrent rectal cancer: a systematic review.
AB  - BACKGROUND: Many patients with rectal cancer receive radiotherapy as a component
      of primary multimodality treatment. Although local recurrence is infrequent,
      reirradiation may be needed to improve resectability and outcomes. This
      systematic review investigated the effects of reirradiation in terms of
      feasibility, toxicity, and long-term outcomes. METHODS: A Medline, Embase and
      Cochrane search resulted in 353 titles/abstracts. Ten publications describing
      seven prospective or retrospective studies were included, presenting results of
      375 patients reirradiated for rectal cancer. RESULTS: Median initial radiation
      dose was 50.4Gy, median 8-30months before reirradiation. Reirradiation was mostly
      administered using hyperfractionated (1.2-1.5Gy twice-daily) or 1.8Gy once-daily
      chemoradiotherapy. Median total dose was 30-40Gy to the gross tumour volume with
      2-4cm margins. Median survival was 39-60months in resected patients and 12
      16months in palliative patients. Good symptomatic relief was reported in 82-100%.
      Acute toxicity with diarrhoea was reported in 9-20%, late toxicity was
      insufficiently reported. CONCLUSIONS: Reirradiation of rectal cancer to limited
      volumes is feasible. When curative resection is possible, the goal is radical
      resection and long-term survival, and hyperfractionated chemoradiotherapy should
      be preferred to limit late toxicity. Reirradiation yielded good symptomatic
      relief in palliative treatment.

PMID- 25613396
TI  - Proposed revision of CT-based cervical and thoracic lymph node levels for
      esophageal cancer in UICC 7th version.
AB  - BACKGROUND AND PURPOSE: To propose revisions of CT-based cervical and thoracic
      lymph node levels for esophageal cancer in UICC 7th version. MATERIAL AND
      METHODS: One hundred and forty-nine patients who underwent surgery were analyzed
      retrospectively for hypothesis validation, 338 patients who underwent definitive
      radiotherapy to evaluate the feasibility in clinical work, and 121 patients from
      another independent cohort for external evaluation. We redefined Level VI in the
      RTOG consensus guideline of CT-based cervical lymph node levels, and established
      a new Level 1 in the IASLC guideline of CT-based thoracic lymph node levels. We
      also shrunk Level 3p. Lymph nodes were assigned into different levels by three
      criteria. RESULTS: We encountered stratification problems in 63 patients by JSED
      criteria and in 24 patients by RTOG criteria. Multivariate analysis showed that
      nodal status was independently associated with OS in the three cohorts (p<0.001).
      No significant difference was found between the Level 1 only group and the
      mediastinal nodes only group (p>0.05). CONCLUSIONS: The proposed hypothesis
      clearly defined the boundary area between the cervical and thoracic parts,
      brought more convenience for stratification, better predicted patients' OS and
      provided information for both pre-treatment evaluation and multidisciplinary
      treatment planning.

PMID- 25613397
TI  - Ewing sarcoma in adults treated with modern radiotherapy techniques.
AB  - BACKGROUND AND PURPOSE: To evaluate local control and survival outcomes in adults
      with Ewing sarcoma (ES) treated with radiotherapy (RT). MATERIAL AND METHODS:
      Retrospective review of all 109 patients age ?18 treated for ES with RT to the
      primary site at Memorial Sloan Kettering Cancer Center between 1990 and 2011. RT
      was used as the definitive local control modality in 44% of patients,
      preoperatively for 6%, and postoperatively for 50%. RESULTS: Median age at
      diagnosis was 27years (range, 18-67). The 5-year local failure (LF) was 18%.
      Differences in LF were not identified when evaluated by modality of local control
      (RT versus combined surgery and RT), RT dose, fractionation, and RT technique.
      However, margin status at time of resection significantly predicted LF. The 5
      year event-free survival and overall survival rates were 44% and 66% for patients
      with localized disease, compared with 16% and 26% for metastatic disease
      (p=0.0005 and 0.0002). Tumor size, histopathologic response to chemotherapy, and
      treatment on or according to a protocol were also significantly associated with
      survival. CONCLUSIONS: This series of adults treated with modern chemotherapy and
      RT had prognostic factors and outcomes similar to adolescents with ES. All adults
      with ES should be treated with an aggressive, multidisciplinary approach.

PMID- 25613398
TI  - Metal artefact reduction in MRI at both 1.5 and 3.0 T using slice encoding for
      metal artefact correction and view angle tilting.
AB  - OBJECTIVE: To compare metal artefact reduction in MRI at both 3.0 T and 1.5 T
      using different sequence strategies. METHODS: Metal implants of stainless steel
      screw and plate within agarose phantoms and tissue specimens as well as three
      patients with implants were imaged at both 1.5 T and 3.0 T, using view angle
      tilting (VAT), slice encoding for metal artefact correction with VAT (SEMAC-VAT)
      and conventional sequence. Artefact reduction in agarose phantoms was
      quantitatively assessed by artefact volume measurements. Blinded reads were
      conducted in tissue specimen and human imaging, with respect to artefact size,
      distortion, blurring and overall image quality. Wilcoxon and Friedman tests for
      multiple comparisons and intraclass correlation coefficient (ICC) for
      interobserver agreement were performed with a significant level of p < 0.05.
      RESULTS: Compared with conventional sequences, SEMAC-VAT significantly reduced
      metal artefacts by 83% +/- 9% for the screw and 89% +/- 3% for the plate at 1.5
      T; 72% +/- 7% for the screw and 38% +/- 13% for the plate at 3.0 T (p < 0.05). In
      qualitative analysis, SEMAC-VAT allowed for better visualization of tissue
      structures adjacent to the implants and produced better overall image quality
      with good interobserver agreement for both tissue specimen and human imaging (ICC
      = 0.80-0.99; p < 0.001). In addition, VAT also markedly reduced metal artefacts
      compared with conventional sequence, but was inferior to SEMAC-VAT. CONCLUSION:
      SEMAC-VAT and VAT techniques effectively reduce artefacts from metal implants
      relative to conventional imaging at both 1.5 T and 3.0 T. ADVANCES IN KNOWLEDGE:
      The feasibility of metal artefact reduction with SEMAC-VAT was demonstrated at
      3.0-T MR. SEMAC-VAT significantly reduced metal artefacts at both 1.5 and 3.0 T.
      SEMAC-VAT allowed for better visualization of the tissue structures adjacent to
      the metal implants. SEMAC-VAT produced consistently better image quality in both
      tissue specimen and human imaging.

PMID- 25613399
TI  - Transvaginal cervical length and amniotic fluid index: can it predict delivery
      latency following preterm premature rupture of membranes?
AB  - OBJECTIVE: We sought to determine whether transvaginal cervical length (TVCL),
      amniotic fluid index (AFI), or a combination of both can predict delivery latency
      within 7 days in women presenting with preterm premature rupture of membranes
      (PPROM). STUDY DESIGN: This was a prospective observational study of TVCL
      measurements in 106 singleton pregnancies with PPROM between 23-33 weeks.
      Delivery latency was defined as the period (in days) from the initial TVCL after
      PPROM to delivery of the infant, with our primary outcome being delivery within 7
      days of TVCL. The independent predictability of significant characteristics for
      delivery within 7 days was determined using multiple logistic regression.
      Sensitivity, specificity, and predictive values were used to examine whether the
      presence of a short TVCL, AFI, or a combination of both affected the risk of
      delivery within 7 days. RESULTS: Delivery within 7 days occurred in 51/106 (48%)
      of pregnancies. Median duration (interquartile range) from PPROM to delivery and
      TVCL to delivery was 8 days (4.0-16.0) and 8 days (3.0-15.0), respectively. Using
      multiple regression TVCL as a continuous variable (odds ratio, 0.65; 95%
      confidence interval, 0.44-0.97; P < .05), AFI <=5 cm (odds ratio, 4.69; 95%
      confidence interval, 1.58-13.93; P < .01) were determined to be independent
      predictors of delivery within 7 days. In all, 42 women (40%) had a TVCL <=2 cm,
      while 62 (59%) had AFI <=5 cm. A total of 26 women (25%) had a combination of
      both TVCL <=2 cm and AFI <=5 cm, while 28 women (27%) had neither characteristic.
      The predictive value of delivery within 7 days for a TVCL <=2 cm was 62%, and for
      an AFI <=5 cm was 58%. Having a combination of low TVCL and low AFI did not
      increase the predictive value of delivery within 7 days (58%). In contrast, only
      3 of 27 women (11%) with neither characteristic delivered within 7 days. The
      predictive value of delivery >7 days for TVCL >2 cm alone was 61%. This
      predictive value changed when analyzed in conjunction with an AFI <=5 cm and >5
      cm at 42% and 89%, respectively. CONCLUSION: A shorter TVCL and an AFI <=5 cm
      independently predict delivery within 7 days in women presenting with PPROM. The
      combination of an AFI >5 cm and TVCL >2 cm greatly improved the potential to
      remain undelivered at 7 days following cervical length assessment. These findings
      may be helpful for counseling and optimizing maternal and neonatal care in women
      with PPROM.

PMID- 25613400
TI  - Effect of vibration frequency on agonist and antagonist arm muscle activity.
AB  - PURPOSE: This study aimed to assess the effect of vibration frequency (f out) on
      the electromyographic (EMG) activity of the biceps brachii (BB) and triceps
      brachii (TB) muscles when acting as agonist and antagonist during static
      exercises with different loads. METHODS: Fourteen healthy men were asked to hold
      a vibratory bar as steadily as possible for 10 s during lying row (pulling) and
      bench press (pushing) exercise at f out of 0 (non-vibration condition), 18, 31
      and 42 Hz with loads of 20, 50, and 80 % of the maximum sustainable load (MSL).
      The root mean square of the EMG activity (EMGRMS) of the BB and TB muscles was
      expressed as a function of the maximal EMGRMS for respective muscles to
      characterize agonist activation and antagonist coactivation. RESULTS: We found
      that (1) agonist activation was greater during vibration (42 Hz) compared to non
      vibration exercise for the TB but not for the BB muscle (p < 0.05); (2)
      antagonist activation was greater during vibration compared to non-vibration
      exercise for both BB (p < 0.01) and TB (p < 0.05) muscles; (3) the vibration
      induced increase in antagonist coactivation was proportional to vibration f out
      in the range 18-42 Hz and (4) the vibration-induced increase in TB agonist
      activation and antagonist coactivation occurred at all loading conditions in the
      range 20-80 % MSL. CONCLUSION: The use of high vibration frequencies within the
      range of 18-42 Hz can maximize TB agonist activation and antagonist activation of
      both BB and TB muscles during upper limb vibration exercise.

PMID- 25613401
TI  - Circadian rhythm of heart rate and physical activity in nurses during day and
      night shifts.
AB  - PURPOSE: The study investigates if the circadian rhythm of heart rate is apparent
      during the working periods of day and night shifts in Swiss and Japanese nurses
      and if it is influenced by work organization. For a better interpretation of the
      heart rate, the activity profile over these working periods was monitored.
      METHODS: Heart rate and activity profile of 18 Swiss and 24 Japanese nurses were
      measured during one day and one night shift. The day and the night shift data of
      each subject were combined, resulting in an approximately 18-h working period.
      RESULTS: A significant time effect of the mean hourly value of the heart rate was
      found in Swiss nurses (change in amplitude 7.1 bpm) as well as in Japanese nurses
      (11.8 bpm). These effects could be modeled with cosine curves for the Swiss and
      Japanese subjects. For the activity level significant time effects, similar to
      the ones in heart rate, were found in Swiss nurses (87 % of SD) but not in
      Japanese nurses (26 % of SD). CONCLUSIONS: We found a significant time effect in
      heart rate similar to the known circadian rhythm under normal sleep-wake
      conditions while working in the studied shift work schedules. In the Japanese
      nurses, studied heart rate followed a circadian rhythm independently of the level
      of physical activity. Therefore, an activity profile following the circadian
      rhythm, especially a reduced workload from 2 to 4 a.m., is proposed. The proposed
      activity profile could be reached with an adapted work organization.

PMID- 25613402
TI  - A 35-day bed rest does not alter the bilateral deficit of the lower limbs during
      explosive efforts.
AB  - PURPOSE: Bilateral deficit (BLD) occurs when the force (or power) generated by
      both limbs together is smaller than the sum of the forces (or powers) developed
      separately by the two limbs. The amount of BLD can be altered by neural
      adaptations brought about by the repetitive execution of specific motor tasks
      (training). Prolonged disuse also leads to relevant neural adaptations; however,
      its effects on BLD are still unknown. Thus, the aim of this study was to
      investigate the effects of a 35-day bed rest on the BLD of the lower limbs.
      METHODS: Ten young healthy volunteers performed maximal explosive efforts on a
      sledge ergometer with both lower limbs or with the right and the left limb
      separately. Electromyography (EMG) of vastus lateralis, rectus femoris, biceps
      femoris and gastrocnemius medialis was also measured. RESULTS: Before bed rest,
      maximal explosive power and peak force were significantly higher in monolateral
      than bilateral efforts (+18.7 and +31.0 %, respectively). Conversely, peak
      velocity was 11.9 % greater in bilateral than monolateral efforts. BLD attained a
      value of 18.1 % and was accompanied by lower EMG amplitude of knee extensors (
      17.0 %) and gastrocnemius medialis (-11.7 %) during bilateral efforts. Bed rest
      led to a ~28.0 % loss in both bilateral and monolateral maximal explosive power.
      Neither BLD magnitude nor the difference in EMG amplitudes as well as in peak
      force and velocity between bilateral and monolateral efforts were affected by bed
      rest. CONCLUSIONS: These results suggest that the neuromuscular factors
      underlying BLD are unaltered after prolonged disuse.

PMID- 25613403
TI  - Antiviral properties from plants of the Mediterranean flora.
AB  - Natural products are a successful source in drug discovery, playing a significant
      role in maintaining human health. We investigated the in vitro cytotoxicity and
      antiviral activity of extracts from 18 traditionally used Mediterranean plants.
      Noteworthy antiviral activity was found in the extract obtained from the branches
      of Daphne gnidium L. against human immunodeficiency virus type-1 (EC50 = 0.08
      MUg/mL) and coxsackievirus B5 (EC50 = 0.10 MUg/mL). Other relevant activities
      were found against BVDV, YFV, Sb-1, RSV and HSV-1. Interestingly, extracts from
      Artemisia arborescens L. and Rubus ulmifolius Schott, as well as those from D.
      gnidium L., showed activities against two different viruses. This extensive
      antiviral screening allowed us to identify attractive activities, offering
      opportunities to develop lead compounds with a great pharmaceutical potential.

PMID- 25613404
TI  - Contralateral upper tract urothelial carcinoma after nephroureterectomy: the
      predictive role of DNA methylation.
AB  - BACKGROUND: Aberrant methylation of genes is one of the most common epigenetic
      modifications involved in the development of urothelial carcinoma. However, it is
      unknown the predictive role of methylation to contralateral new upper tract
      urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We
      retrospectively investigated the predictive role of DNA methylation and other
      clinicopathological factors in the contralateral upper tract urothelial carcinoma
      (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center
      cohort of patients. METHODS: In a retrospective design, methylation of 10 genes
      was analyzed on tumor specimens belonging to 664 consecutive patients treated by
      RNU for primary UTUC. Median follow-up was 48 mo (range: 3-144 mo). Gene
      methylation was accessed by methylation-sensitive polymerase chain reaction, and
      we calculated the methylation index (MI), a reflection of the extent of
      methylation. The log-rank test and Cox regression were used to identify the
      predictor of contralateral UTUC recurrence. RESULTS: Thirty (4.5%) patients
      developed a subsequent contralateral UTUC after a median follow-up time of 27.5
      (range: 2-139) months. Promoter methylation for at least one gene promoter locus
      was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were
      seen in the tumors with contralateral UTUC recurrence than the tumors without
      contralateral recurrence. High MI (P = 0.007) was significantly correlated with
      poor cancer-specific survival. Multivariate analysis indicated that unmethylated
      RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P =
      0.009), history of renal transplantation (P < 0.001), and preoperative renal
      insufficiency (P = 0.002) are independent risk factors for contralateral UTUC
      recurrence after RNU. CONCLUSIONS: Our data suggest a potential role of DNA
      methylation in predicting contralateral UTUC recurrence after RNU. Such
      information could help identify patients at high risk of new contralateral UTUC
      recurrence after RNU who need close surveillance during follow up.

PMID- 25613405
TI  - Overlapping neural circuits for visual attention and eye movements in the human
      cerebellum.
AB  - Previous research in patients with cerebellar damage suggests that the cerebellum
      plays a role in covert visual attention. One limitation of some of these studies
      is that they examined patients with heterogeneous cerebellar damage. As a result,
      the patterns of reported deficits have been inconsistent. In the current study,
      we used functional neuroimaging (fMRI) in healthy adults (N=14) to examine
      whether or not the cerebellum plays a role in covert visual attention.
      Participants performed two covert attention tasks in which they were cued
      exogenously (with peripheral flashes) or endogenously (using directional arrows)
      to attend to marked locations in the visual periphery without moving their eyes.
      We compared BOLD activation in these covert attention conditions to a number of
      control conditions including: the same attention tasks with eye movements, a
      target detection task with no cueing, and a self-paced button-press task.
      Subtracting these control conditions from the covert attention conditions allowed
      us to effectively remove the contribution of the cerebellum to motor output. In
      addition to the usual fronto-parietal networks commonly engaged by these
      attention tasks, lobule VI of the vermis in the cerebellum was also activated
      when participants performed the covert attention tasks with or without eye
      movements. Interestingly, this effect was larger for exogenous compared to
      endogenous cueing. These results, in concert with recent patient studies, provide
      independent yet converging evidence that the same cerebellar structures that are
      involved in eye movements are also involved in visuospatial attention. 

PMID- 25613406
TI  - Distinct expression profiles of lncRNAs between regressive and mature scars.
AB  - BACKGROUND: Recent studies suggest that long non-coding RNAs (lncRNAs) play
      crucial roles in human diseases. The function of lncRNAs in abnormal scar
      pathogenesis remains poorly understood. METHODS: In this study, we examined the
      lncRNAs expression profiles among regressive and mature scars following caesarean
      sections. A total of 30,586 lncRNAs and 26,109 mRNAs were analyzed by microarrays
      (Human LncRNA Array v3.0, Arraystar, Inc.). RESULTS: In total, we identified
      1,871 lncRNAs and 817 mRNAs with differential expression between regressive and
      mature scar individuals (fold change>=3, p<=0.001). A set of differentially
      expressed lncRNA transcripts, in particular, lncRNA8975-1, AC097662.2 and RP11
      586K2.1, were confirmed using qRT-PCR. Gene ontology and pathway analysis
      revealed that compared to mature scars, many processes over-represented in
      regressive scars are related to the immune system. CONCLUSION: Our results show
      significantly altered expression profiles of lncRNAs and mRNAs between regressive
      and mature scars. These transcripts are potential molecular targets for
      inhibiting abnormal scar formation following caesarean sections.

PMID- 25613407
TI  - CORR Insights((r)): There Are No Differences in Short- to Mid-term Survivorship
      Among Total Hip-bearing Surface Options: A Network Meta-analysis.

PMID- 25613408
TI  - CORR Insights(r): Retrieval analysis of sequentially annealed highly crosslinked
      polyethylene used in total hip arthroplasty.

PMID- 25613409
TI  - CORR Insights(r): Does Patient Sex Affect the Rate of Mortality and Complications
      After Spine Surgery? A Systematic Review.

PMID- 25613410
TI  - A review of virus removal in wastewater treatment pond systems.
AB  - Wastewater treatment ponds (lagoons) are one of the most common types of
      technologies used for wastewater management worldwide, especially in small cities
      and towns. They are particularly well-suited for systems where the effluent is
      reused for irrigation. However, the efficiency of virus removal in wastewater
      treatment pond systems is not very well understood. The main objective of this
      paper is to critically review the major findings related to virus removal in
      wastewater treatment pond systems and to statistically analyze results reported
      in the literature from field studies on virus removal in these systems. A
      comprehensive analysis of virus removal reported in the literature from 71
      different wastewater treatment pond systems reveals only a weak to moderate
      correlation of virus removal with theoretical hydraulic retention time. On
      average, one log10 reduction of viruses was achieved for every 14.5-20.9 days of
      retention, but the 95th percentile value of the data analyzed was 54 days. The
      mechanisms responsible for virus removal in wastewater treatment ponds were also
      reviewed. One recent finding is that sedimentation may not be a significant virus
      removal mechanism in some wastewater ponds. Recent research has also revealed
      that direct and indirect sunlight-mediated mechanisms are not only dependent on
      pond water chemistry and optics, but also on the characteristics of the virus and
      its genome. MS2 coliphage is considered to be the best surrogate for studying
      sunlight disinfection in ponds. The interaction of viruses with particles, with
      other microorganisms, and with macroinvertebrates in wastewater treatment ponds
      has not been extensively studied. It is also unclear whether virus
      internalization by higher trophic-level organisms has a protective or a
      detrimental effect on virus viability and transport in pond systems. Similarly,
      the impact of virus-particle associations on sunlight disinfection in ponds is
      not well understood. Future research should focus on the interactions of viruses
      with particles and with other organisms, as well as the development of a model
      for virus removal in pond systems that can be used for design purposes, and to
      inform future editions of the WHO Guidelines for Wastewater Use in Agriculture. 

PMID- 25613411
TI  - Modification of ultrafiltration membrane with nanoscale zerovalent iron layers
      for humic acid fouling reduction.
AB  - Nanoscale zerovalent iron (NZVI) was layered onto ultrafiltration (UF) membrane
      surface and tested for antifouling properties using humic acid (HA). Scanning
      electron microscopy showed that a relatively homogeneous layer was formed across
      the membrane surface by NZVI particles. Strong adhesion was observed between NZVI
      and UF membrane used. HA was significantly removed and membrane flux was
      increased in the presence of NZVI layer. Increased loadings of NZVI onto the
      membrane surface increased resistance to fouling while slightly reducing the
      clean water permeability of the membrane. However, the pore size of the layer
      formed by pristine NZVI was large, resulting in more chances of HA molecules
      getting to the membrane surface even blocking the membrane pores at the
      beginning. Membrane loaded with NZVI layer performed much better under acidic
      conditions. During NZVI synthesis, specific surface area of NZVI particle
      increased with increasing the ratio of ethanol (Vethanol/Vsolution), which also
      gradually decreased the average pore size of NZVI layer. As a result, the
      corresponding membrane flux steadily increased. Additionally, the results for
      permeate samples under different conditions showed that large molecular weight
      (MW, >30 kDa) and medium MW HA molecules (3-30 kDa) were removed much faster than
      those of small MW HA molecules (<3 kDa). 

PMID- 25613412
TI  - Performance of calcium peroxide for removal of endocrine-disrupting compounds in
      waste activated sludge and promotion of sludge solubilization.
AB  - Removal of six phenolic endocrine disrupting compounds (EDCs) (estrone, 17beta
      estradiol, 17alpha-ethinylestradiol, estriol, bisphenol A, and 4-nonylphenols)
      from waste activated sludge (WAS) was investigated using calcium peroxide (CaO2)
      oxidation. Effects of initial pH and CaO2 dosage were investigated. The impacts
      of CaO2 treatment on sludge solubilization and anaerobic digestion were also
      evaluated. Specifically, the role of reactive oxygen species (ROS) in EDC
      degradation during CaO2 oxidation was tested. Effects of 6 metal ions contained
      in the sludge matrix on EDC degradation were also evaluated. The results showed
      that CaO2 treatment can be a promising technology for EDC removal and
      facilitating sludge reuse. The EDC removal efficiencies increased with the
      increase in CaO2 dosage. At CaO2 doses of more than 0.34 g per gram of total
      solid (g g(-1) TS), more than 50% of EDCs were removed in a wide pH range of 2
      12. Higher removal efficiencies were achieved at initial pH values of 12 and 2.
      The products of EDCs during CaO2 oxidation had less estrogenic activity than the
      originals. Under the conditions of neutral pH and CaO2 dosage = 0.34 g g(-1) TS,
      the sludge solubilization can be improved by increasing the soluble total organic
      carbon (STOC) and volatile suspended solids (VSS) reduction by 25% and 27% in 7
      d, respectively; the volatile fatty acid (VFA) production was enhanced by 96% in
      the 15 d following anaerobic digestion. The ROS released by CaO2 are the main
      factors contributing to EDC removal, among which, hydroxyl radicals (OH) play the
      most important role. Metal ions contained in the sludge matrix also affected EDC
      removal. For most cases, Fe, Cu, and Zn had positive effects; Mn and Ag had
      negative effects; and Mg had an insignificant effect on EDC removal. 

PMID- 25613413
TI  - Motor function in interpolar microtubules during metaphase.
AB  - We analyze experimental motility assays of microtubules undergoing small
      fluctuations about a "balance point" when mixed in solution of two different
      kinesin motor proteins, KLP61F and Ncd. It has been proposed that the microtubule
      movement is due to stochastic variations in the densities of the two species of
      motor proteins. We test this hypothesis here by showing how it maps onto a one
      dimensional random walk in a random environment. Our estimate of the amplitude of
      the fluctuations agrees with experimental observations. We point out that there
      is an initial transient in the position of the microtubule where it will
      typically move of order its own length. We compare the physics of this gliding
      assay to a recent theory of the role of antagonistic motors on restricting
      interpolar microtubule sliding of a cell's mitotic spindle during prometaphase.
      It is concluded that randomly positioned antagonistic motors can restrict
      relative movement of microtubules, however they do so imperfectly. A variation in
      motor concentrations is also analyzed and shown to lead to greater control of
      spindle length.

PMID- 25613414
TI  - Helical assemblies: structure determinants.
AB  - Protein structural motifs such as helical assemblies and alpha/beta barrels
      combine secondary structure elements with various types of interactions. Helix
      helix interfaces of assemblies - Ankyrin, ARM/HEAT, PUM, LRR, and TPR repeats -
      exhibit unique amino acid composition and patterns of interactions that correlate
      with curvature of solenoids, surface geometry and mutual orientation of the
      helical edges. Inner rows of ankyrin, ARM/HEAT, and PUM-HD repeats utilize edges
      (i-1, i) and (i+1, i+2) for the interaction of the given alpha-helix with
      preceding and following helices correspondingly, whereas outer rows of these
      proteins and LRR repeats invert this pattern and utilize edges (i-1, i) and (i-3,
      i-2). Arrangement of contacts observed in protein ligands that bind helical
      assemblies has to mimic the assembly pattern to provide the same curvature as a
      determinant of binding specificity. These characteristics are important for
      understanding fold recognition, specificity of protein-protein interactions, and
      design of new drugs and materials.

PMID- 25613415
TI  - Bisphosphonate-related osteonecrosis of the palatal torus.
AB  - BACKGROUND: Bisphosphonates are widely used for the treatment of osteoporosis and
      other bone-degrading disorders; however, bisphosphonate therapy is an important
      risk factor for osteonecrosis of the jaws. METHODS: We report a rare case of
      bisphosphonate-related osteonecrosis of the palatal torus. RESULTS: The patient
      was a 72-year-old woman with osteoporosis who had received 35 mg alendronate
      sodium hydrate once every week for 6 years. She had a 2-month history of oral
      pain because of intractable mucositis and ulceration of the palatal torus, with
      no history of malignant disease, radiation therapy, chemotherapy, steroid use, or
      recent dentoalveolar surgery. A CT scan showed a bony prominence at the
      midportion of the hard palate with erosion of its cortex. Her condition was
      diagnosed as stage 2 bisphosphonate-related osteonecrosis of the jaw caused by
      trauma, and she was advised to discontinue alendronate. She was prescribed oral
      antibiotics for 5 days and an oral antibacterial rinse. The mucositis with
      ulceration healed in approximately 10 weeks, but left a small scar. CONCLUSIONS:
      Although osteonecrosis of the palatal torus associated with bisphosphonate use is
      a rare condition, otolaryngologists should consider this condition in the
      differential diagnosis of intractable ulceration of the hard palate.

PMID- 25613416
TI  - Symptom Checklist-90-Revised scores in adult children exposed to alienating
      behaviors: an Italian sample.
AB  - This study addresses a particular form of child psychological maltreatment,
      exposing a child to alienating behaviors in the context of a high degree of
      conflict between the parents. The objective of this research was to identify
      retrospectively the alienating behaviors that occurred in an Italian sample of
      children and the reported associated psychosocial symptoms. Seven hundred and
      thirty-nine adults in Chieti, Italy, completed an anonymous and confidential
      survey regarding their childhood exposure to parental alienating behaviors and
      measures of current symptomatology. About 75% of the sample reported some
      exposure to parental alienating behaviors; 15% of the sample endorsed the item,
      "tried to turn me against the other parent." The results revealed strong and
      statistically significant associations between reported exposure to parental
      alienating behaviors and reports of current symptomatology. 

PMID- 25613417
TI  - Cloning and characterization of ifitm1 and ifitm3 expression during early
      zebrafish development.
AB  - The family of interferon-inducible transmembrane proteins (IFITMs) plays a
      crucial role in inhibiting proliferation, promoting homotypic cell adhesion and
      mediating germ cell development. In the present study, the full-length cDNAs of
      zebrafish ifitm1 (744 bp) and ifitm3 (702 bp) were obtained by rapid
      amplification of cDNA ends (RACE). Reverse transcription polymerase chain
      reaction (RT-PCR) analysis showed that ifitm1 mRNA was expressed in the ovary,
      testis, brain, muscle, liver and kidney, while ifitm3 mRNA was only detected in
      the ovary. Based on in situ hybridization, ifitm1 mRNA was found to be strongly
      expressed in the ooplasm from stage I to stage II and ifitm3 mRNA was also
      strongly expressed in the ooplasm from stage I to stage II, furthermore ifitm3
      expression ultimately localized to the cortex region beneath the plasma membrane
      of stage IV oocytes. During development, ifitm1 expression was initially detected
      in the enveloping layer cells and deep layer cells of shield stage embryos. Then,
      throughout the segmentation phase (10.25-24 hours post-fertilization (hpf)),
      ifitm1 expression was mainly detected in the head, trunk and tail regions. Unlike
      ifitm1, ifitm3 expression was initially detected in sphere stage embryos and was
      then broadly expressed throughout the embryo from the 70% epiboly stage to 24
      hpf. Interestingly, ifitm3 was also expressed in primordial germ cells (PGCs)
      from the bud stage to 24 hpf. This expression analysis indicates that zebrafish
      ifitm1 may play a critical role in early organogenesis and may perform immune or
      hematopoietic functions and ifitm3 might be necessary for PGC migration and the
      formation of female germ cells. 

PMID- 25613418
TI  - Tendon needling for treatment of tendinopathy: A systematic review.
AB  - OBJECTIVE: To summarize the best available evidence to determine if tendon
      needling is an effective treatment for tendinopathy. Data source. Medline and
      Cochrane Databases through November 2013. REVIEW METHODS: Utilizing the search
      terms tendinopathy, needle, needling, tenotomy, dry needling, needling tendon,
      needle fenestration, and tendon fenestration, 17 articles were identified through
      our systematic literature search. Of these, 4 studies met the inclusion criteria.
      Four independent reviewers reviewed the articles. The study results and generated
      conclusions were agreed upon. RESULTS: The studies that were included in this
      review suggest that tendon needling improves patient reported outcomes in
      patients with tendinopathy. In 2 studies evaluating tendon needling in lateral
      epicondylosis, one showed an improvement in a subjective visual analogue scale
      score of 34% (significant change > 25%) from baseline at 6 months. The other
      showed an improvement of 56.1% in a visual analogue scale score from baseline. In
      1 study evaluating tendon needling in addition to eccentric therapy for Achilles
      tendinosis, the subjective Victorian Institute of Sport Assessment-Achilles (VISA
      A) score improved by 19.9 (significant change > 10) (95% CI, 13.6-26.2) from
      baseline. In 1 study evaluating tendon needling in rotator cuff tendinosis, the
      subjective shoulder pain and disability index showed statistical significant
      improvement from baseline at 6 months (P < 0.05). CONCLUSIONS: The evidence
      suggests that tendon needling improves patient-reported outcome measures in
      patients with tendinopathy. There is a trend that shows that the addition of
      autologous blood products may further improve theses outcomes.

PMID- 25613419
TI  - Part-whole information assists in topological * topological but not in
      orientation * orientation conjunction searches.
AB  - Visual search is a routine task used in everyday life and is an important field
      of research in cognitive psychology. In laboratory settings, it has been shown
      that search for a target defined by a unique conjunction of two colours is more
      efficient if one colour surrounds the other (a part-whole search) compared to
      when no such hierarchical structural relationship exists (a part-part search;
      Wolfe et al. in Perception & Psychophysics, 55, 537, 1994). A similar result has
      been shown to hold for size * size conjunction searches (Bilsky & Wolfe in
      Perception & Psychophysics, 57, 749, 1995). We show that this result also holds
      for topology * topology conjunction searches (where the stimuli are either hollow
      or filled), but not for orientation * orientation conjunction searches. We use
      the simultaneous-sequential paradigm to investigate a possible reason for the
      inefficiency of part-whole orientation search compared with the efficiency of
      part-whole searches of other features. We argue that two different attribute
      values from the same dimension can be processed independently, without
      interfering with each other for colour, size, and topology, but not for
      orientation. Because it is obviously more efficient to process a conjunction
      stimulus when both components of the conjunction can be processed without mutual
      interference, it follows that colour * colour, size * size, and topological *
      topology part-whole conjunction searches are likely to be more efficient than
      orientation * orientation part-whole conjunction searches. 

PMID- 25613420
TI  - Perceived difficulty of a motor task affects memory but not action.
AB  - Successful motor interaction with a target changes memory of the target's size,
      which seems larger if the action was successful than if it was unsuccessful. This
      has been attributed to the effect of action on subsequent perception or memory.
      We asked what the action provides: Is feedback from the action necessary, or only
      the information provided by the action? We found that perceived difficulty alone
      changes the remembered goal characteristics, without changes in the stimuli, and
      before the motor task is executed. We gave observers a marble and showed them a
      hole in a box. They were told that throwing the marble into the hole was either
      difficult or easy, depending on the condition. The hole was then covered and its
      size judged. Participants who were told that the task was difficult judged the
      hole to be significantly smaller than it was, whereas those told that the task
      was easy made judgements not significantly different from veridical. When
      observers subsequently threw the marble, their success rates were independent of
      their own estimates of hole size or of what they had been told about the
      difficulty of the task, showing that their size estimates affected memory but not
      action. In a second experiment, we found that the effect disappeared if the hole
      was visible during the size estimation. 

PMID- 25613422
TI  - Ten-year mortality in older patients attending the emergency department after a
      fall.
AB  - AIM: To determine the dependency scores, long-term mortality and factors
      associated with mortality in older people presenting to the emergency department
      (ED) with a fall. METHODS: Information on sociodemographics, dependency using the
      Barthel index and fall characteristics were collected from consecutive patients
      attending the ED over a 6-month period. Barthel score was reassessed at 12
      months. Ten-year mortality data were obtained through the National Registry
      Department. RESULTS: A total of 198 participants, with a mean age (standard
      deviation) of 76.2 years (6.3 years) and 74% women, were recruited. Of these, 70%
      sustained falls indoors, while 49% of falls occurred between 06.00 to 12.00
      hours. Total Barthel scores were significantly lower at 1-year follow up compared
      with baseline (median [interquartile range], 20 [2] vs 18 [5], P < 0.001). Age
      >=75 years was significantly associated with mortality at 1, 3, 5 and 10 years
      (HR 3.12, 95% CI 1.48-6.56; HR 2.32, 95% CI 1.37-3.92; HR 1.87, 95% CI 1.21-2.88;
      and HR 2.25, 95% CI 1.60-3.17, respectively). Indoor falls (HR 2.54, 95% CI 1.07
      6.06; HR 2.01, 95% CI 1.10-3.69), hospital admission (HR 2.16, 95% CI 1.14-4.10;
      HR 1.84, 95% CI 1.11-3.07) and Barthel <=18 (HR 2.99, 95% CI 1.39-6.44; HR 2.47,
      95% CI 1.40-4.33) were significantly associated with 1-year and 3-year mortality.
      Hospital admission (HR 1.94, 95% CI 1.24-3.01; HR 1.53, 95% CI 1.06-2.23) and
      Barthel <=18 (HR 2.27, 95% CI 1.41-3.66; HR 1.85, 95% CI 1.27-2.68) remained
      significantly associated with increased mortality at 5 and 10 years. CONCLUSION:
      Functional ability is significantly reduced at 1 year after an initial
      presentation to the ED with a fall. Mortality is increased at 1 and 3 years in
      fallers who experienced indoor falls. The excess mortality associated with
      hospital admission and lower disability scores is persistent at 5 and 10 years.
      The results of the present study are invaluable in prognostication and healthcare
      decision-making for this group of frail older patients.

PMID- 25613421
TI  - Dppa3 expression is critical for generation of fully reprogrammed iPS cells and
      maintenance of Dlk1-Dio3 imprinting.
AB  - Reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs)
      often generates partially reprogrammed iPSCs (pre-iPSCs), low-grade chimera
      forming iPSCs (lg-iPSCs) and fully reprogrammed, high-grade chimera production
      competent iPSCs (hg-iPSCs). Lg-iPSC transcriptome analysis revealed misregulated
      Dlk1-Dio3 cluster gene expression and subsequently the imprinting defect at the
      Dlk1-Dio3 locus. Here, we show that germ-cell marker Dppa3 is present only in lg
      iPSCs and hg-iPSCs, and that induction with exogenous Dppa3 enhances
      reprogramming kinetics, generating all hg-iPSCs, similar to vitamin C (Vc).
      Conversely, Dppa3-null fibroblasts show reprogramming block at pre-iPSCs state
      and Dlk1-Dio3 imprinting defect. At the molecular level, we show that Dppa3 is
      associated with Dlk1-Dio3 locus and identify that Dppa3 maintains imprinting by
      antagonizing Dnmt3a binding. Our results further show molecular parallels between
      Dppa3 and Vc in Dlk1-Dio3 imprinting maintenance and suggest that early
      activation of Dppa3 is one of the cascades through which Vc facilitates the
      generation of fully reprogrammed iPSCs. 

PMID- 25613423
TI  - Factors influencing lymph node metastasis in patients with ampullary
      adenocarcinoma.
AB  - AIM: In cases of ampullary carcinoma, lymph node involvement affects the
      selection of treatment strategies. This study aimed to identify clinicopathologic
      features of ampullary carcinoma with lymph node metastases. METHODS: The records
      of 74 consecutive patients with ampullary adenocarcinoma who underwent
      pancreaticoduodenectomy (PD) with regional lymph node dissection were
      retrospectively analyzed. RESULTS: Twenty-two patients (30%) with lymph node
      metastasis had significantly worse survival after resection than those without
      lymph node metastasis (p = 0.017). Univariate analyses revealed that preoperative
      biliary drainage; elevated serum carbohydrate antigen 19-9 (>=36 U/ml); moderate
      to-poor pathologic grade (G2/3); perineural, vascular, lymphatic, pancreas, and
      duodenal invasion; and T category were significantly associated with lymph node
      metastasis. In multivariate analysis, only pathologic grade (G2/3) remained
      significantly associated with lymph node metastasis (hazard ratio, 6.51; p =
      0.035). In sub-classified analysis for T category, lymph node metastasis was
      found in 5 of 22 cases (22.7%) of T1 tumors. Four of five cases with lymph node
      metastases had a dominant G2/3 component, whereas only 2 of 17 cases without
      lymph node metastases had a G2/3 component in T1 tumors (p = 0.0036).
      CONCLUSIONS: Pathologic grade (G2/3) was significantly and independently
      associated with lymph node metastasis and was also a significant predictor in T1
      tumor cases.

PMID- 25613424
TI  - A competing risks approach to "biologic" interaction.
AB  - In epidemiology, the concepts of "biologic" and "statistical" interactions have
      been the subject of extensive debate. We present a new approach to biologic
      interaction based on Rothman's original (Am J Epidemiol, 104:587-592, 1976)
      discussion of sufficient causes. We do this in a probabilistic framework using
      competing risks and argue that sufficient cause interaction between two factors
      can be evaluated via the parameters in a particular statistical model, the
      additive hazard rate model. We present empirical conditions for presence of
      sufficient cause interaction and an example based on data from a liver cirrhosis
      trial illustrates the ideas. 

PMID- 25613425
TI  - GM3 and cancer.
AB  - Our studies during the early 1970s showed that expression of GM3, the simplest
      ganglioside and an abundant animal cell membrane component, is reduced during
      malignant transformation of cells by oncogenic viruses. Levels of mRNA for GM3
      synthase were reduced in avian and mammalian cells transformed by oncoprotein "v
      Jun", and overexpression of GM3 synthase in the transformed cells caused
      reversion from transformed to normal cell-like phenotype. GM3 has a well
      documented inhibitory effect on activation of growth factor receptors (GFRs),
      particularly epidermal GFR (EGFR). De-N-acetyl GM3, which is expressed in some
      invasive human cancer cells, has an enhancing effect on EGFR activation. The
      important role of the sialosyl group of GM3 was demonstrated using NEU3, a plasma
      membrane-associated sialidase that selectively remove sialic acids from
      gangliosides GM3 and GD1a and is up-regulated in many human cancer cells. GM3 is
      highly enriched in a type of membrane microdomain termed "glycosynapse", and
      forms complexes with co-localized cell signaling molecules, including Src family
      kinases, certain tetraspanins (e.g., CD9, CD81, CD82), integrins, and GFRs (e.g.,
      fibroblast growth factor receptor and hepatocyte growth factor receptor c-Met).
      Studies by our group and others indicate that GM3 modulates cell adhesion,
      growth, and motility by altering molecular organization in glycosynaptic
      microdomains and the activation levels of co-localized signaling molecules that
      are involved in cancer pathogenesis. 

PMID- 25613426
TI  - Educational outcomes following breech delivery: a record-linkage study of 456947
      children.
AB  - BACKGROUND: Obstetric management of term breech infants changed dramatically
      following the Term Breech Trial which suggested increased serious neonatal
      morbidity following trial of labour. Short-term morbidity is a poor proxy of long
      term neurological sequelae. We determined whether vaginal breech delivery was
      associated with educational outcomes. METHODS: We linked three Scotland-wide
      administrative databases at an individual level: the ScotXed school census;
      Scottish Qualifications Authority (SQA) examination results; and Scottish
      Morbidity Record (SMR02) maternity database. The linkage provided information on
      singleton children, born at term, attending Scottish schools between 2006 and
      2011. RESULTS: Of the 456 947 eligible children, 1574 (0.3%) had vaginal breech
      deliveries, 12 489 (2.7%) planned caesarean section for breech presentation and
      442 090 (96.9%) vaginal cephalic deliveries. The percentage of term breech
      infants delivered vaginally fell from 23% to 7% among children who started school
      in 2006 and 2011, respectively. Of children born by vaginal breech delivery, 1.5%
      had a low 5-min Apgar score (<=3) compared with only 0.4% of those born by either
      breech caesarean section [adjusted odds ratio (OR) 6.16, 95% confidence interval
      (CI) 4.44-8.54, p<0.001] or cephalic vaginal delivery (adjusted OR 3.84, 95% CI
      2.99-4.93, p<0.001). Children born by vaginal breech delivery had lower
      examination attainment than those born by either planned caesarean section for
      breech presentation (adjusted OR 1.16, 95% CI 1.02-1.32, p=0.020) or vaginal
      cephalic delivery (adjusted OR 1.14, 95% CI 1.01-1.28, p=0.029). CONCLUSIONS:
      Vaginal delivery of term breech infants was associated with lower examination
      attainment, as well as poorer Apgar scores, suggesting that the adverse effects
      are not just short-term.

PMID- 25613427
TI  - Cohort Profile: The HealthNuts Study: Population prevalence and
      environmental/genetic predictors of food allergy.
AB  - HealthNuts is a single-centre, multi-wave, population-based longitudinal study
      designed to assess prevalence, determinants, natural history and burden of
      allergy (particularly food allergy) in the early years of life. It is novel in
      the use of serial food challenge measures within its population frame to confirm
      food allergy. The cohort comprises 5276 children initially recruited at age 12
      months from council-run immunization sessions across Melbourne, Australia. As
      well as parent-completed questionnaires and researcher-observed eczema status,
      all infants underwent skin-prick testing to egg, peanut, sesame and either cow's
      milk or shellfish, and those with detectable wheals underwent food challenges to
      determine clinical allergy. In wave 2, conducted at age 4 years, validated
      questionnaires collected data on asthma, allergic rhinitis (hay fever), eczema
      and food allergies. Food challenges were repeated in children previously
      identified as food allergic to determine resolution. In wave 3, all children
      (irrespective of food allergy status) were invited for clinical assessment at age
      6 years, including lung function, physical measurements, skin-prick testing to
      foods and aeroallergens and food challenges if food sensitized. Biological
      specimens (blood, cheek swabs) were collected at each wave for ancillary
      immunological, genetic and epigenetic studies. Applications to access data and/or
      samples can be submitted to [katrina.allen@mcri.edu.au]. 

PMID- 25613429
TI  - The application of second-order approximation of Taylor series in thickness shear
      vibration analysis of quartz crystal microbalances.
AB  - The inertia force caused by an additional mass layer is usually adopted to
      simulate the effective mechanical boundary condition in a quartz crystal
      microbalance (QCM), which may yield incorrect results when the upper layer
      becomes relative thicker. Thus, a detail analysis of the thickness shear
      vibration in a QCM for detecting the characteristics of the upper isotropic layer
      is proceeded based on a second-order approximation of Taylor series. The result
      calculated by this method has a higher accuracy than that of inertial-force
      approximation. According to these outcomes, the free and forced vibration has
      been illustrated, as well as transient effects during the switching on/off
      processes or under a sudden fluctuation of the driving-voltage amplitude or
      frequency. It has been revealed by numerical simulation that the additional mass
      layer has a great influence on the mechanical performance of QCM, including the
      resonance frequency, amplitudes of displacement and admittance, response time of
      the transient processes, and so on. These findings can prove effective guidance
      for physical phenomenon explanations and experimental measurement in mass sensor
      devices. 

PMID- 25613430
TI  - GATA-Binding Factor 6 Contributes to Atrioventricular Node Development and
      Function.
AB  - BACKGROUND: Several transcription factors regulate cardiac conduction system
      (CCS) development and function but the role of each in specifying distinct CCS
      components remains unclear. GATA-binding factor 6 (GATA6) is a zinc-finger
      transcription factor that is critical for patterning the cardiovascular system.
      However, the role of GATA6 in the embryonic heart and CCS has never been shown.
      METHODS AND RESULTS: We report that Gata6 is expressed abundantly in the proximal
      CCS during midgestation in mice. Myocardial-specific deletion of the carboxyl
      zinc-finger of Gata6 induces loss of hyperpolarizing cyclic nucleotide-gated
      channel, subtype 4 staining in the compact atrioventricular node with some
      retention of hyperpolarizing cyclic nucleotide-gated channel, subtype 4 staining
      in the atrioventricular bundle, but has no significant effect on the connexin-40
      positive bundle branches. Furthermore, myocardial-specific deletion of the
      carboxyl zinc-finger of Gata6 alters atrioventricular conduction in postnatal
      life as assessed by surface and invasive electrophysiological evaluation, as well
      as decreasing the number of ventricular myocytes and inducing compensatory
      myocyte hypertrophy. Myocardial-specific deletion of the carboxyl zinc-finger of
      Gata6 is also associated with downregulation of the transcriptional repressor ID2
      and the cardiac sodium-calcium exchanger NCX1 in the proximal CCS, where GATA6
      transactivates both of these factors. Finally, carboxyl zinc-finger deletion of
      Gata6 reduces cell-cycle exit of TBX3+ myocytes in the developing
      atrioventricular bundle during the period of atrioventricular node specification,
      which results in fewer TBX3+ cells in the proximal CCS of mature mutant mice.
      CONCLUSIONS: GATA6 contributes to the development and postnatal function of the
      murine atrioventricular node by promoting cell-cycle exit of specified
      cardiomyocytes toward a conduction system lineage.

PMID- 25613431
TI  - Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan
      Syndrome.
AB  - BACKGROUND: It has been shown that losartan reduces aortic dilatation in patients
      with Marfan syndrome. However, treatment response is highly variable. This study
      investigates losartan effectiveness in genetically classified subgroups. METHODS
      AND RESULTS: In this predefined substudy of COMPARE, Marfan patients were
      randomized to daily receive losartan 100 mg or no losartan. Aortic root
      dimensions were measured by MRI at baseline and after 3 years. FBN1 mutations
      were classified based on fibrillin-1 protein effect into (1) haploinsufficiency,
      decreased amount of normal fibrillin-1, or (2) dominant negative, normal
      fibrillin-1 abundance with mutant fibrillin-1 incorporated in the matrix. A
      pathogenic FBN1 mutation was found in 117 patients, of whom 79 patients were
      positive for a dominant negative mutation (67.5%) and 38 for a mutation causing
      haploinsufficiency (32.5%). Baseline characteristics between treatment groups
      were similar. Overall, losartan significantly reduced aortic root dilatation rate
      (no losartan, 1.3+/-1.5 mm/3 years, n=59 versus losartan, 0.8+/-1.4 mm/3 years,
      n=58; P=0.009). However, losartan reduced only aortic root dilatation rate in
      haploinsufficient patients (no losartan, 1.8+/-1.5 mm/3 years, n=21 versus
      losartan 0.5+/-0.8 mm/3 years, n=17; P=0.001) and not in dominant negative
      patients (no losartan, 1.2+/-1.7 mm/3 years, n=38 versus losartan 0.8+/-1.3 mm/3
      years, n=41; P=0.197). CONCLUSIONS: Marfan patients with haploinsufficient FBN1
      mutations seem to be more responsive to losartan therapy for inhibition of aortic
      root dilatation rate compared with dominant negative patients. Additional
      treatment strategies are needed in Marfan patients with dominant negative FBN1
      mutations. CLINICAL TRIAL REGISTRATION:
      http://www.trialregister.nl/trialreg/index.asp; Unique Identifier: NTR1423.

PMID- 25613428
TI  - Risk factors for head and neck cancer in young adults: a pooled analysis in the
      INHANCE consortium.
AB  - BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults
      has been reported. We aimed to compare the role of major risk factors and family
      history of cancer in HNC in young adults and older patients. METHODS: We pooled
      data from 25 case-control studies and conducted separate analyses for adults <=
      45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old
      ('older adults', 17700 cases and 22 704 controls). Using logistic regression with
      studies treated as random effects, we estimated adjusted odds ratios (ORs) and
      95% confidence intervals (CIs). RESULTS: The young group of cases had a higher
      proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified
      oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx
      cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or
      never drinkers among female cases were higher than among male cases in both age
      groups. Positive associations with HNC and duration or pack-years of smoking and
      drinking were similar across age groups. However, the attributable fractions
      (AFs) for smoking and drinking were lower in young when compared with older
      adults (AFs for smoking in young women, older women, young men and older men,
      respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%,
      52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0%
      (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of
      early-onset cancer was associated with HNC risk in the young [OR=2.27 (95%
      CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The
      attributable fraction for family history of early-onset cancer was 23.2% (8.60%
      to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults.
      CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The
      lower AF of cigarette smoking and alcohol drinking in young adults may be due to
      the reduced length of exposure due to the lower age. Other characteristics, such
      as those that are inherited, may play a more important role in HNC in young
      adults compared with older adults.

PMID- 25613432
TI  - The application of valgus urethral mucosa anastomosis in the operation of
      posterior urethral stricture.
AB  - PURPOSE: To evaluate the safety and efficacy of valgus mucosa anastomosis in
      posterior urethra reconstruction. METHODS: We retrospectively reviewed the
      medical records of 116 patients who had undergone anastomotic repair of posterior
      urethral strictures between 2009 and 2013. Seventy-six patients underwent valgus
      urethral mucosa anastomosis (group A), and 40 underwent traditional end-to-end
      anastomosis (group B). The voiding status, complication rate, and adjuvant
      therapy were compared between the two groups. The clinical outcome was considered
      a failure when any postoperative intervention was needed. RESULTS: Patient age
      ranged from 11 to 68 years (mean 38.2 +/- 10.6). Follow-up was 5-59 months (mean
      19.5 +/- 13.2). The estimated urethral stricture length was 0.5-3.5 cm (mean 1.85
      +/- 0.40). Of all patients, the number of patients with simple stricture and
      complicated stricture were 47 and 69 respectively, and there was no significant
      difference in the complexity of stricture between group A and group B (60.5 vs.
      57.5%, P > 0.05). Besides, there was no significant difference in the follow-up
      time and length of stricture between the two groups (31.6 +/- 12.0 vs. 35.1 +/-
      14.8 months, P > 0.05). Compared to group B, the operation success rate in group
      A was greatly improved (92.1 vs. 80%, P < 0.05), while the incidence of
      complication was similar between the two groups (31.6 vs. 27.5%, P > 0.05).
      CONCLUSIONS: The valgus urethral mucosa anastomosis could significantly improve
      the operation success rate of end-to-end anastomosis, reduce the stricture
      recurrence rate, improve the long-term urination function, and not increase the
      incidence of complications. So, valgus urethral mucosa anastomosis is an easy,
      effective and reliable urethral anastomosis technique.

PMID- 25613433
TI  - A very simple formula to compute pCO2 in hemodialysis patients.
AB  - PURPOSE: To identify mixed acid-base disorders, clinicians must estimate the
      value of partial pressure of carbonic dioxide (pCO2), complying with the reduced
      plasma bicarbonate concentration (HCO3). What is the most appropriate equation
      relating the two quantities in chronic hemodialysis patients remains unknown.
      Chronic hemodialysis patients remains unknown, which motivates our study.
      METHODS: Among a large database of blood gas analysis from chronic hemodialysis
      patients, we selected 291 blood samples showing HCO3 < 24 mmol/L and, among
      these, we further selected a subset of samples claimed for pure metabolic
      acidosis. A linear approximation based upon the least-square criterion was
      adopted to derive the best-fit equation. The differences between this and other
      commonly used formulas were computed in terms of root mean square (RMS) errors.
      RESULTS: In chronic hemodialysis patients, the reduction in pCO2 due to metabolic
      acidosis is better predicted multiplying by 1.2 the reduction in HCO3, or by
      using the expression pCO2 = HCO3 + 15; the two approaches lead to almost the same
      results. In contrast, the equation pCO2 = 1.5 * HCO3 + 8, known as Winters'
      formula, exhibits larger errors. CONCLUSIONS: The easy-to-use expression pCO2 =
      HCO3 + 15 seems suitable for the daily clinical practice in hemodialysis
      patients. However, if HCO3 value is lower than 12 mmol/L, a threshold at which
      different formulas return almost the same value, also Winters' formula, derived
      in the 60's from patients with low values of HCO3, could be used.

PMID- 25613434
TI  - Assessing landscape scale wildfire exposure for highly valued resources in a
      Mediterranean area.
AB  - We used a fire simulation modeling approach to assess landscape scale wildfire
      exposure for highly valued resources and assets (HVR) on a fire-prone area of 680
      km(2) located in central Sardinia, Italy. The study area was affected by several
      wildfires in the last half century: some large and intense fire events threatened
      wildland urban interfaces as well as other socioeconomic and cultural values.
      Historical wildfire and weather data were used to inform wildfire simulations,
      which were based on the minimum travel time algorithm as implemented in FlamMap.
      We simulated 90,000 fires that replicated recent large fire events in the area
      spreading under severe weather conditions to generate detailed maps of wildfire
      likelihood and intensity. Then, we linked fire modeling outputs to a geospatial
      risk assessment framework focusing on buffer areas around HVR. The results
      highlighted a large variation in burn probability and fire intensity in the
      vicinity of HVRs, and allowed us to identify the areas most exposed to wildfires
      and thus to a higher potential damage. Fire intensity in the HVR buffers was
      mainly related to fuel types, while wind direction, topographic features, and
      historically based ignition pattern were the key factors affecting fire
      likelihood. The methodology presented in this work can have numerous
      applications, in the study area and elsewhere, particularly to address and inform
      fire risk management, landscape planning and people safety on the vicinity of
      HVRs. 

PMID- 25613435
TI  - Invasive ductal carcinoma arising within a large mammary hamartoma.

PMID- 25613436
TI  - Erectile dysfunction and obstructive sleep apnea: from mechanisms to a distinct
      phenotype and combined therapeutic strategies.

PMID- 25613437
TI  - Determinants of the electric field during transcranial direct current
      stimulation.
AB  - Transcranial direct current stimulation (tDCS) causes a complex spatial
      distribution of the electric current flow in the head which hampers the accurate
      localization of the stimulated brain areas. In this study we show how various
      anatomical features systematically shape the electric field distribution in the
      brain during tDCS. We constructed anatomically realistic finite element (FEM)
      models of two individual heads including conductivity anisotropy and different
      skull layers. We simulated a widely employed electrode montage to induce motor
      cortex plasticity and moved the stimulating electrode over the motor cortex in
      small steps to examine the resulting changes of the electric field distribution
      in the underlying cortex. We examined the effect of skull thickness and
      composition on the passing currents showing that thinner skull regions lead to
      higher electric field strengths. This effect is counteracted by a larger
      proportion of higher conducting spongy bone in thicker regions leading to a more
      homogenous current over the skull. Using a multiple regression model we could
      identify key factors that determine the field distribution to a significant
      extent, namely the thicknesses of the cerebrospinal fluid and the skull, the
      gyral depth and the distance to the anode and cathode. These factors account for
      up to 50% of the spatial variation of the electric field strength. Further, we
      demonstrate that individual anatomical factors can lead to stimulation "hotspots"
      which are partly resistant to electrode positioning. Our results give valuable
      novel insights in the biophysical foundation of tDCS and highlight the importance
      to account for individual anatomical factors when choosing an electrode montage. 

PMID- 25613440
TI  - [Management and costs of chronic pulmonary obstructive disease in France in
      2011].
AB  - OBJECTIVES: To estimate the prevalence of treated chronic obstructive pulmonary
      disease (COPD) and its associated costs by stage of severity. METHODS: The study
      was conducted on the 2011 data of the french general beneficiary sample database
      (EGB). EGB is a 1/97th sample of the whole population of the beneficiaries of the
      main compulsory national health insurances. COPD cases and the level of severity
      of the disease have been identified using new algorithms established from the
      available parameters in EGB. Costs were estimated using a collective perspective.
      RESULTS: The minimal prevalence of treated COPD was estimated at 3.8% in patients
      of 40 years and older and 1.9% regardless of the age of individuals. This
      population was predominantly male (58.2%) with a mean age of 68.8 years (+/
      12.7). A total of 6.2% of patients had a health-care utilization suggestive of a
      very severe stage of COPD and 8.1%, 13.8% and 71.9% suggestive of severe,
      moderate and mild stages respectively. Over one year, 28.8% of patients visited a
      specialist respiratory physician, 5.0% were hospitalized (>=24h) for COPD and
      6.7% died. Patients experienced an average of 1.7 (+/-1.5) exacerbations per year
      and only 61.4% received specific pharmacological treatment for COPD during the
      year. The average yearly health-care cost of a patient with COPD was estimated at
      ?9382, with ?5342 directly related to COPD. CONCLUSION: This study based on
      medico-administrative databases confirms the high epidemiological and economic
      burden of COPD in France.

PMID- 25613438
TI  - Functional resting-state connectivity of the human motor network: differences
      between right- and left-handers.
AB  - Handedness is associated with differences in activation levels in various motor
      tasks performed with the dominant or non-dominant hand. Here we tested whether
      handedness is reflected in the functional architecture of the motor system even
      in the absence of an overt motor task. Using resting-state functional magnetic
      resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain
      functional connectivity maps of the primary motor cortex (M1), supplementary
      motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal
      junction and motor putamen were compared between right- and left-handers. We
      further used a multivariate linear support vector machine (SVM) classifier to
      reveal the specificity of brain regions for classifying handedness based on
      individual resting-state maps. Using left M1 as seed region, functional
      connectivity analysis revealed stronger interhemispheric functional connectivity
      between left M1 and right PMd in right-handers as compared to left-handers. This
      connectivity cluster contributed to the individual classification of right- and
      left-handers with 86.2% accuracy. Consistently, also seeding from right PMd
      yielded a similar handedness-dependent effect in left M1, albeit with lower
      classification accuracy (78.1%). Control analyses of the other resting-state
      networks including the speech and the visual network revealed no significant
      differences in functional connectivity related to handedness. In conclusion, our
      data revealed an intrinsically higher functional connectivity in right-handers.
      These results may help to explain that hand preference is more lateralized in
      right-handers than in left-handers. Furthermore, enhanced functional connectivity
      between left M1 and right PMd may serve as an individual marker of handedness. 

PMID- 25613439
TI  - BrainPrint: a discriminative characterization of brain morphology.
AB  - We introduce BrainPrint, a compact and discriminative representation of brain
      morphology. BrainPrint captures shape information of an ensemble of cortical and
      subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace
      Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes.
      This discriminative characterization enables new ways to study the similarity
      between brains; the focus can either be on a specific brain structure of interest
      or on the overall brain similarity. We highlight four applications for BrainPrint
      in this article: (i) subject identification, (ii) age and sex prediction, (iii)
      brain asymmetry analysis, and (iv) potential genetic influences on brain
      morphology. The properties of BrainPrint require the derivation of new algorithms
      to account for the heterogeneous mix of brain structures with varying
      discriminative power. We conduct experiments on three datasets, including over
      3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and
      236 MRI scans from the VETSA twin study. All processing steps for obtaining the
      compact representation are fully automated, making this processing framework
      particularly attractive for handling large datasets. 

PMID- 25613441
TI  - Abdominal obesity, hypertension, antihypertensive medication use and biochemical
      recurrence of prostate cancer after radical prostatectomy.
AB  - BACKGROUND: The aim of this study was to determine whether abdominal obesity,
      including visceral adipose tissue (VAT) measured by computed tomography and blood
      pressure (BP) were associated with biochemical recurrence of prostate cancer
      after prostatectomy. METHODS: We investigated 283 patients who underwent radical
      prostatectomy for prostate cancer retrospectively. We obtained information on
      body mass index (BMI), waist circumference (WC), VAT, BP, antihypertensive drug
      use, pretreatment prostate-specific antigen levels, pathological Gleason scores
      and postoperative surgical margin status. Hypertension was defined as systolic BP
      (SBP)?130mmHg or diastolic BP?85mmHg. RESULTS: Among 283 patients, 41 (14%)
      developed biochemical recurrence subsequently. We performed a Cox proportional
      hazard regression analysis to assess the association of each obesity measurement
      and SBP with biochemical recurrence using clinical predictors as potential
      confounders. No association was observed between any obesity measurement assessed
      and biochemical recurrence. Adjusting for each of BMI, WC and VAT, a higher SBP
      was associated significantly with biochemical recurrence (hazard ratio [HR],
      adjusted for VAT=1.04; 95% confidence interval [CI]=1.02-1.07). Adjusting for
      obesity (BMI?25kg/m(2)), hypertension was also associated significantly with
      biochemical recurrence (HR=2.08; 95% CI=1.09-3.97). Compared with normotensive
      patients, those with untreated and uncontrolled hypertension had a significantly
      increased risk of biochemical recurrence (HR=2.45; 95% CI=1.06-5.66).
      CONCLUSIONS: A higher BP and untreated, uncontrolled hypertension were
      independent risk factors for biochemical recurrence after prostatectomy. Control
      of hypertension could be an important treatment strategy for preventing
      biochemical recurrence.

PMID- 25613442
TI  - Diabetes, smoking, alcohol use, and family history of cancer as risk factors for
      pancreatic neuroendocrine tumors: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Risk factors for pancreatic neuroendocrine tumors (PNETs)
      are not well understood. The aim of this systematic review was to assess if
      diabetes mellitus, smoking, alcohol use, and family history of cancer are risk
      factors for PNETs. METHODS: MEDLINE and abstracts from the European and North
      American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for
      studies published until October 2013. Eligible studies were selected according to
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      statement. RESULTS: Five studies evaluating 4 individual populations were
      included (study accrual period 2000-2011) into the meta-analysis, involving 827
      cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All
      studies had a case-control design and described regional series. The pooled
      adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I(2) = 60.4%) for
      history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I(2) = 45.8%) for ever
      smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I(2) = 0.0%) for heavy smoking, 1.09
      (95% CI: 0.64-1.85; p = 0.75; I(2) = 85.2%) for ever alcohol use, 2.72 (95% CI:
      1.25-5.91; p = 0.01; I(2) = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64
      2.85; p < 0.01; I(2) = 0.0%) for first-degree family history of cancer.
      CONCLUSIONS: Diabetes mellitus and first-degree family history of cancer are
      associated with an increased risk of sporadic PNET. There was also a trend for
      diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a
      risk factor for PNET, but there was considerable heterogeneity in the meta
      analysis. These results suggest the need for a larger, homogeneous, international
      study for the clarification of risk factors for the occurrence of PNET.

PMID- 25613443
TI  - The problems of long-term treatment with benzodiazepines and related substances.
AB  - BACKGROUND: Benzodiazepine abuse and dependence have been recognized and widely
      discussed for more than 40 years. With more than 230 million daily doses
      prescribed in Germany per year, the burden of reimbursement on the statutory
      health insurance carriers is high, albeit with a slight decline from year to
      year. At present, about 50% of all prescriptions in Germany are issued privately,
      even for patients who have statutory health insurance. METHODS: We selectively
      review the literature on the epidemiology and treatment of benzodiazepine
      dependence and abuse in Germany. RESULTS: Estimates of the number of
      benzodiazepine-dependent persons in Germany range from 128 000 to 1.6 million.
      Most estimates take no account of the large number of private prescriptions
      (i.e., those that are not reimbursed by the statutory health insurance scheme),
      while many exclude prescriptions for elderly persons, for whom these drugs are
      frequently prescribed. For the outpatient treatment of benzodiazepine withdrawal,
      it is recommended that the drug should first be switched to an equivalent dose of
      another benzodiazepine with an intermediate or long-acting effect; the dose
      should then, in general, be reduced weekly. In case of consumption of a high dose
      (>= 20 mg diazepam equivalent), hospitalization and the additional administration
      of carbamazepine or valproic acid are recommended. Flumazenil treatment can
      improve with - drawal symptoms and leads to higher abstinence rates.
      Antidepressants should be given only if the patient is depressed. The dependence
      potential of nonbenzodiazepine drugs such as zolpidem and zopiclon must also be
      borne in mind. CONCLUSION: Benzodiazepines are generally highly effective when
      first given, but they should generally be given only for strict indications and
      for a limited time. If these drugs still need to be given beyond the short term,
      timely referral to a specialist is indicated, and possibly also contact with the
      addiction aid system.

PMID- 25613444
TI  - Many questions left open.

PMID- 25613445
TI  - Positive scientific approach.

PMID- 25613446
TI  - Mistletoe treatment as homeopathic magic.

PMID- 25613447
TI  - Several flaws.

PMID- 25613448
TI  - New drug for the treatment of inoperable pancreatic cancer?

PMID- 25613449
TI  - Unsustainable claims.

PMID- 25613450
TI  - In reply.

PMID- 25613451
TI  - More questions left open than answered.

PMID- 25613452
TI  - Carpal and cubital tunnel and other, rarer nerve compression syndromes.
AB  - BACKGROUND: Carpal tunnel syndrome is by far the most common peripheral nerve
      compression syndrome, affecting approximately one in every six adults to a
      greater or lesser extent. Splitting the flexor retinaculum to treat carpal tunnel
      syndrome is the second most common specialized surgical procedure in Germany.
      Cubital tunnel syndrome is rarer by a factor of 13, and the other compression
      syndromes are rarer still. METHODS: This review is based on publications
      retrieved by a selective literature search of PubMed and the Cochrane Library,
      along with current guidelines and the authors' clinical and scientific
      experience. RESULTS: Randomized controlled trials have shown, with a high level
      of evidence, that the surgical treatment of carpal tunnel syndrome yields very
      good results regardless of the particular technique used, as long as the
      diagnosis and the indication for surgery are well established by the
      electrophysiologic and radiological findings and the operation is properly
      performed. The success rates of open surgery, and the single-portal and dual
      portal endoscopic methods are 91.6%, 93.4% and 92.5%, respectively. When
      performed by experienced hands, all these procedures have complication rates
      below 1%. The surgical treatment of cubital tunnel syndrome has a comparably low
      complication rate, but worse results overall. Neuro-ultrasonography and magnetic
      resonance imaging (neuro-MRI) are increasingly being used to complement the
      diagnostic findings of electrophysiologic studies. CONCLUSION: Evidence-based
      diagnostic methods and treatment recommendations are now available for the two
      most common peripheral nerve compression syndromes. Further controlled trials are
      needed for most of the rarer syndromes, especially the controversial ones.

PMID- 25613453
TI  - Genome-wide analyses of LINE-LINE-mediated nonallelic homologous recombination.
AB  - Nonallelic homologous recombination (NAHR), occurring between low-copy repeats
      (LCRs) >10 kb in size and sharing >97% DNA sequence identity, is responsible for
      the majority of recurrent genomic rearrangements in the human genome. Recent
      studies have shown that transposable elements (TEs) can also mediate recurrent
      deletions and translocations, indicating the features of substrates that mediate
      NAHR may be significantly less stringent than previously believed. Using >4 kb
      length and >95% sequence identity criteria, we analyzed of the genome-wide
      distribution of long interspersed element (LINE) retrotransposon and their
      potential to mediate NAHR. We identified 17 005 directly oriented LINE pairs
      located <10 Mbp from each other as potential NAHR substrates, placing 82.8% of
      the human genome at risk of LINE-LINE-mediated instability. Cross-referencing
      these regions with CNVs in the Baylor College of Medicine clinical chromosomal
      microarray database of 36 285 patients, we identified 516 CNVs potentially
      mediated by LINEs. Using long-range PCR of five different genomic regions in a
      total of 44 patients, we confirmed that the CNV breakpoints in each patient map
      within the LINE elements. To additionally assess the scale of LINE-LINE/NAHR
      phenomenon in the human genome, we tested DNA samples from six healthy
      individuals on a custom aCGH microarray targeting LINE elements predicted to
      mediate CNVs and identified 25 LINE-LINE rearrangements. Our data indicate that
      LINE-LINE-mediated NAHR is widespread and under-recognized, and is an important
      mechanism of structural rearrangement contributing to human genomic variability. 

PMID- 25613454
TI  - Supramolecular spectrally encoded microgels with double strand probes for
      absolute and direct miRNA fluorescence detection at high sensitivity.
AB  - We present novel microgels as a particle-based suspension array for direct and
      absolute microRNA (miRNA) detection. The microgels feature a flexible molecular
      architecture, antifouling properties, and enhanced sensitivity with a large
      dynamic range of detection. Specifically, they possess a core-shell molecular
      architecture with two different fluorescent dyes for multiplex spectral analyses
      and are endowed with a fluorescent probe for miRNA detection. Encoding and
      detection fluorescence signals are distinguishable by nonoverlapping emission
      spectra. Tunable fluorescence probe conjugation and emission confinement on
      single microgels allow for ultrasensitive miRNA detection. Indeed, the suspension
      array has high selectivity and sensitivity with absolute quantification, a
      detection limit of 10(-15) M, a dynamic range from 10(-9) to 10(-15) M, and
      higher accuracy than qRT-PCR. The antifouling properties of the microgels also
      permit the direct measurement of miRNAs in serum, without sample pretreatment or
      target amplification. A multiplexed assay has been tested for a set of miRNAs
      chosen as cancer biomarkers. 

PMID- 25613455
TI  - Exploring evidence for a prospective relationship between common mental disorder
      and meeting residential mobility preferences.
AB  - This study investigates evidence of a selective influence of mental health in
      meeting residential mobility preferences. Data from two waves of Understanding
      Society (the UK Household Longitudinal Study) were used to identify four
      preference-mobility groups ('desired stayers', 'entrapped', 'desired movers',
      'displaced'). Associations between mental health (symptoms of common mental
      disorder, CMD) and preference-mobility groups were measured both before and after
      residential moves. Those identified with CMD at baseline were at greater risk of
      being both in the 'entrapped' and the 'desired mover' groups, relative to the
      'desired stayer' group in the following year. The association between preference
      mobility group and subsequent poorer mental health was found among both groups
      that failed to meet their mobility preferences ('entrapped' and 'displaced').
      This study finds evidence for a selective influence of mental health - such that
      those with poorer mental health are less likely to achieve a desired residential
      move, and highlights the importance of considering a bidirectional relationship
      between residential mobility and mental health. 

PMID- 25613457
TI  - Total synthesis of (-)-caprazamycin A.
AB  - Caprazamycin A has significant antibacterial activity against Mycobacterium
      tuberculosis (TB). The first total synthesis is herein reported and features a)
      the scalable preparation of the syn-beta-hydroxy amino acid with a thiourea
      catalyzed diastereoselective aldol reaction, b) construction of a diazepanone
      with an unstable fatty-acid side chain, and c) global deprotection with
      hydrogenation. This report provides a route for the synthesis of related
      liponucleoside antibiotics with fatty-acid side chains. 

PMID- 25613456
TI  - Clinical factors associated with negative urinary antigen tests implemented for
      the diagnosis of community-acquired pneumococcal pneumonia in adult patients.
AB  - OBJECTIVE: This study investigated clinical factors associated with negative
      urinary antigen tests (UAT) implemented for the diagnosis of pneumococcal
      community-acquired pneumonia (CAP) in adult patients. SUBJECTS AND METHODS: We
      reviewed the medical records of 755 adult patients who completed the UAT in our
      hospital between 2009 and 2012. Of these, we evaluated 63 patients with
      bacteriologically confirmed definite pneumococcal CAP (33 were UAT-positive, and
      30 were UAT-negative). RESULTS: There was no significant difference between the
      UAT-positive and the UAT-negative patients regarding age, dehydration,
      respiratory failure, orientation, blood pressure (ADROP) score (the CAP severity
      score proposed by the Japanese Respiratory Society), gender, white blood cell
      counts, liver/kidney function tests, or urinalysis. However, serum C-reactive
      protein (CRP) concentrations were 31% lower in the UAT-negative patients than in
      the UAT-positive patients (p = 0.02). Furthermore, the prothrombin time
      international normalized ratio was 50% higher in the UAT-negative patients than
      in the UAT-positive patients, although the difference did not reach statistical
      significance (p = 0.06). The prevalence of comorbidities was similar in both UAT
      positive and UAT-negative patients. However, warfarin had been prescribed in 8
      (27%) of the UAT-negative patients compared to only 1 (3%) of the UAT-positive
      patients (odds ratio = 11.6; p = 0.01). CONCLUSIONS: These results suggested that
      low serum CRP concentrations and the use of warfarin increased the possibility
      with which false-negative UAT results occurred in these patients with
      pneumococcal CAP.

PMID- 25613458
TI  - Thymosin beta4 as a restorative/regenerative therapy for neurological injury and
      neurodegenerative diseases.
AB  - Thymosin beta4 (Tbeta4) promotes CNS and peripheral nervous system (PNS)
      plasticity and neurovascular remodeling leading to neurological recovery in a
      range of neurological diseases. Treatment of neural injury and neurodegenerative
      disease 24 h or more post-injury and disease onset with Tbeta4 enhances
      angiogenesis, neurogenesis, neurite and axonal outgrowth, and oligodendrogenesis,
      and thereby, significantly improves functional and behavioral outcomes. We
      propose that oligodendrogenesis is a common link by which Tbeta4 promotes
      recovery after neural injury and neurodegenerative disease. The ability to target
      many diverse restorative processes via multiple molecular pathways that drive
      oligodendrogenesis and neurovascular remodeling may be mediated by the ability of
      Tbeta4 to alter cellular expression of microRNAs (miRNAs). However, further
      investigations on the essential role of miRNAs in regulating protein expression
      and the remarkable exosomal intercellular communication network via exosomes will
      likely provide insight into mechanisms of action and means to amplify the
      therapeutic effects of Tbeta4. 

PMID- 25613459
TI  - Nanoparticles in vaccine delivery.

PMID- 25613462
TI  - Peripartum and neonatal outcomes of small-for-gestational-age infants with
      gastroschisis.
AB  - OBJECTIVES: Neonates with gastroschisis are often small for gestational age (SGA)
      based on population nomograms. Our objective was to evaluate the effect of SGA on
      perinatal and neonatal outcomes in cases of gastroschisis. METHODS: This is a
      retrospective study of neonates with prenatally diagnosed gastroschisis from two
      academic centers between 2008 and 13. Perinatal and neonatal outcomes of neonates
      with SGA at birth were compared with appropriate-for-gestational-age (AGA)
      neonates. The primary composite outcome was defined as any of the following:
      neonatal sepsis, short bowel syndrome at discharge, prolonged mechanical
      ventilation (upper quartile for the cohort), bowel atresia or death. RESULTS: We
      identified 112 cases of gastroschisis, 25 of whom (22%) were SGA at birth. There
      were no differences in adverse peripartum outcomes between SGA and AGA infants.
      No difference was found in the primary composite neonatal outcome (52% vs 36%, p
      = 0.21), but SGA infants were more likely to have prolonged mechanical
      ventilation (44% vs 22%, p = 0.04) and prolonged length of stay (LOS) (52% vs
      22%, p = 0.007). After adjusting for GA at delivery, SGA remained associated with
      prolonged LOS (OR = 4.3, CI: 1.6-11.8). CONCLUSION: Among infants with
      gastroschisis, SGA at birth is associated with a fourfold increase in odds for
      prolonged LOS, independent of GA.

PMID- 25613463
TI  - Achieving planar plasmonic subwavelength resolution using alternately arranged
      insulator-metal and insulator-insulator-metal composite structures.
AB  - This work develops and analyzes a planar subwavelength device with the ability of
      one-dimensional resolution at visible frequencies that is based on alternately
      arranged insulator-metal (IM) and insulator-insulator-metal (IIM) composite
      structures. The mechanism for the proposed device to accomplish subwavelength
      resolution is elucidated by analyzing the dispersion relations of the IM-IIM
      composite structures. Electromagnetic simulations based on the finite element
      method (FEM) are performed to verify that the design of the device has
      subwavelength resolution. The ability of subwavelength resolution of the proposed
      device at various visible frequencies is achieved by slightly varying the
      constituent materials and geometric parameters. The proposed devices have
      potential applications in multi-functional material, real-time super-resolution
      imaging, and high-density photonic components. 

PMID- 25613464
TI  - Effects of Dantrolene Treatment on Ventricular Electrophysiology and
      Arrhythmogenesis in Rats With Chronic beta-Adrenergic Receptor Activation.
AB  - Dantrolene, which is primarily used to treat malignant hyperthermia, has recently
      been suggested for the prevention of arrhythmogenesis in various animal models.
      In this study, the effects of dantrolene treatment on electrophysiological
      properties and ventricular arrhythmias (VAs) in rats with chronic beta-adrenergic
      receptor (beta-AR) activation were investigated. Rats were randomized to
      treatment with saline (control group), isoproterenol (ISO; ISO group), or ISO +
      dantrolene (ID group) for 2 weeks. An electrophysiological study was performed to
      assess action potential duration restitution (APDR) and induce action potential
      duration (APD) alternans or VA in vitro. The protein levels of Cav1.2,
      sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), and ryanodine receptor 2 (RyR2)
      were detected by Western blot. Compared with the control group, chronic
      administration of ISO significantly increased APD, the maximum slope (Smax) of
      APDR curve, and the spatial dispersions of Smax and APD (all P < .01), and all
      effects were attenuated by dantrolene treatment (all P < .05). Additionally,
      chronic ISO administration significantly reduced the protein levels of SERCA2 and
      RyR2, but increased the Cav1.2 protein expression (all P < .05). However,
      compared with the ISO group, dantrolene treatment preserved SERCA2a and RyR2
      protein levels and decreased Cav1.2 protein levels in the ID group (all P < .05).
      The intracellular Ca(2+) ([Ca(2+)]i) levels measured by incubating isolated
      cardiomyocytes with Fluo-3/alveolar macrophages were significantly increased in
      the ISO group compared with the control group (P < .01). Dantrolene treatment
      markedly reduced the rise of [Ca(2+)]i levels caused by chronic administration of
      ISO (P < .05). Dantrolene treatment also prevented the reductions in the APD
      alternans and VA thresholds induced by chronic ISO stimulation (all P < .05).
      These data suggest that dantrolene stabilizes ventricular electrophysiological
      characteristics and increases the expression of key sarcoplasmic reticulum
      calcium cycling proteins to reduce vulnerability to VA in rats with chronic beta
      AR activation. 

PMID- 25613465
TI  - Predicting the Need for Upfront Combination Therapy in Pulmonary Arterial
      Hypertension.
AB  - BACKGROUND: Combination therapy is commonly used for pulmonary arterial
      hypertension (PAH) treatment. We aimed to identify factors that may predict the
      need for future combination therapy. METHODS: We conducted a retrospective chart
      review of consecutive patients with PAH in an aim to describe baseline clinical,
      echocardiogram, and hemodynamic characteristics of patients who eventually
      required combination therapy during the course of their disease and compared them
      to the ones who were maintained on monotherapy. RESULTS: The monotherapy group
      was followed for an average of 31.8 +/- 18.8 months and the combination therapy
      group was followed for an average of 28.7 +/- 13.6 months. Among the 71 patients
      analyzed, a significantly higher number of patients who eventually required
      combination therapy belonged to World Health Organization functional class 3 (45%
      vs 37%) and 4 (23% vs 0) at baseline, compared with those on monotherapy (P <
      .05). Combination group also had a higher Registry to Evaluate Early And Long
      term PAH Disease Management (REVEAL) PAH risk score at presentation. End of 6
      minute walk test (6MWT), oxygen saturation (Spo 2) was also lower in the
      combination therapy group, 86% +/- 8% versus 91% +/- 7% (P < .05). Patients who
      eventually required combination therapy were more frequently noticed to have
      right ventricular enlargement, right atrial enlargement, and had a higher resting
      estimated right ventricular systolic pressure (RVSP). Right heart catheterization
      derived hemodynamics data at baseline showed that the combination therapy group
      had a higher mean pulmonary artery (PA) pressure, lower pulmonary capillary wedge
      pressure, lower cardiac output, and higher pulmonary vascular resistance (PVR).
      On univariate analysis, only PVR >=300 dyne.s/cm(5), mean PA pressure of >=40 mm
      Hg, estimated RVSP >= 60 mm Hg, PAH risk score >= 10, and end of 6MWT saturation
      of <= 90% were of significance. CONCLUSION: Patients with PAH who require
      combination therapy in the course of their disease have worse hemodynamics, PAH
      risk score, functional class, and end of 6MWT oxygen saturation at the time of
      presentation compared to patients maintained on monotherapy.

PMID- 25613466
TI  - Effects of urban density on carbon dioxide exchanges: Observations of dense
      urban, suburban and woodland areas of southern England.
AB  - Anthropogenic and biogenic controls on the surface-atmosphere exchange of CO2 are
      explored for three different environments. Similarities are seen between suburban
      and woodland sites during summer, when photosynthesis and respiration determine
      the diurnal pattern of the CO2 flux. In winter, emissions from human activities
      dominate urban and suburban fluxes; building emissions increase during cold
      weather, while traffic is a major component of CO2 emissions all year round.
      Observed CO2 fluxes reflect diurnal traffic patterns (busy throughout the day
      (urban); rush-hour peaks (suburban)) and vary between working days and non
      working days, except at the woodland site. Suburban vegetation offsets some
      anthropogenic emissions, but 24-h CO2 fluxes are usually positive even during
      summer. Observations are compared to estimated emissions from simple models and
      inventories. Annual CO2 exchanges are significantly different between sites,
      demonstrating the impacts of increasing urban density (and decreasing vegetation
      fraction) on the CO2 flux to the atmosphere. 

PMID- 25613467
TI  - Identification of key amino acid differences between Cyrtorhinus lividipennis and
      Nilaparvata lugens nAChR alpha8 subunits contributing to neonicotinoid
      sensitivity.
AB  - High sensitivity to neonicotinoid insecticides have been reported in the miridbug
      Cyrtorhinus lividipennis, an important predatory enemy of rice planthoppers, such
      as Nilaparvata lugens (brown planthopper). In the present study, the sensitivity
      of neonicotinoid insecticides between C. lividipennis and N. lugens were detected
      and compared. The results showed that neonicotinoid insecticides were much more
      toxic to the miridbug than to the brown planthopper. A nicotinic acetylcholine
      receptor subunit was cloned from the miridbug and denoted as alpha8 subunit
      (Clalpha8) according to sequence similarities and important functional motifs.
      Key amino acid differences were found in specific loops from alpha8 subunits
      between C. lividipennis (Clalpha8) and N. lugens (Nlalpha8). In order to
      understand the roles of key amino acid differences in insecticide sensitivities,
      the different amino acid residues in specific loops of Nlalpha8 were introduced
      into the corresponding sites in Clalpha8 to construct several subunit mutants.
      Clalpha8 or subunit mutants were co-expressed with rat beta2 to obtain the
      functional receptors in Xenopus oocytes. The single mutation N191F in loop B
      reduced imidacloprid sensitivity, with EC50 value in Clalpha8(N191F)/beta2 of
      15.21MUM and 5.74MUM in Clalpha8/beta2. Interestingly, although the single
      mutation E240T in loop C did not cause the significant change in imidacloprid
      sensitivity, it could enhance the effects of N191F and cause more decrease in
      imidacloprid sensitivity. The results indicated that E240T might contribute to
      neonicotinoid sensitivity in an indirect way. 

PMID- 25613469
TI  - [Neuromuscular hamartoma of the orbit: case report and discussion of the role of
      corticosteroids in treatment].
AB  - INTRODUCTION: Neuromuscular hamartoma, also known as neuromuscular choristoma or
      benign triton tumor, is a rare benign tumor of well-differentiated striated
      muscle fibers mixed with peripheral nerve fibers. According to our research, this
      is the sixth case of benign triton tumor of the trigeminal nerve and the third
      case of isolated orbital location reported in the world literature. PURPOSE: To
      report a rare case of orbital neuromuscular hamartoma and discuss the role of
      corticosteroids in the treatment of these lesions for which surgical excision is
      often difficult. OBSERVATION: A 47-year-old woman, with a history of tuberculous
      lymphadenitis treated in 2006, presented with a clinical scenario of inflammatory
      orbitopathy without loss of visual acuity progressing over 20 days. MRI showed a
      lesion centered on the soft tissues of the infero-lateral right orbit. A biopsy
      was performed, showing neuromuscular hamartoma on histology. The patient was put
      on a tapering dose of corticosteroids with clear clinical and anatomical
      improvement. Orbital CT follow-up was obtained two months after discontinuation
      of treatment, confirming the disappearance of the tumor mass. CONCLUSION:
      Hamartoma of the orbit is a very rare entity and may clinically simulate
      malignant neoplasms; the diagnosis is histologic. Given the difficulties
      encountered in the resection of these tumors, we believe that corticosteroids
      might be proposed as an alternative treatment that could modulate inflammation
      and bring about regression or disappearance of the tumor.

PMID- 25613470
TI  - [Retraction of the haptic of an intraocular lens].

PMID- 25613468
TI  - Standardisation of information submitted to an endpoint committee for cause of
      death assignment in a cancer screening trial - lessons learnt from CAP (Cluster
      randomised triAl of PSA testing for Prostate cancer).
AB  - BACKGROUND: In cancer screening trials where the primary outcome is target cancer
      specific mortality, the unbiased determination of underlying cause of death (UCD)
      is crucial. To minimise bias, the UCD should be independently verified by expert
      reviewers, blinded to death certificate data and trial arm. We investigated
      whether standardising the information submitted for UCD assignment in a
      population-based randomised controlled trial of prostate-specific antigen (PSA)
      testing for prostate cancer reduced the reviewers' ability to correctly guess the
      trial arm. METHODS: Over 550 General Practitioner (GP) practices (>415,000 men
      aged 50-69 years) were cluster-randomised to PSA testing (intervention arm) or
      the National Health Service (NHS) prostate cancer risk management programme
      (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews
      of researcher-written clinical vignettes that masked trial arm and death
      certificate information. A period of time after the process began (the initial
      phase), we analysed whether the reviewers could correctly identify trial arm from
      the vignettes, and the reasons for their choice. This feedback led to further
      standardisation of information (second phase), after which we re-assessed the
      extent of correct identification of trial arm. RESULTS: 1099 assessments of 509
      vignettes were completed by January 2014. In the initial phase (n = 510
      assessments), reviewers were unsure of trial arm in 33% of intervention and 30%
      of control arm assessments and were influenced by symptoms at diagnosis, PSA test
      result and study-specific criteria. In the second phase (n = 589), the respective
      proportions of uncertainty were 45% and 48%. The percentage of cases whereby
      reviewers were unable to determine the trial arm was greater following the
      standardisation of information provided in the vignettes. The chances of a
      correct guess and an incorrect guess were equalised in each arm, following
      further standardisation. CONCLUSIONS: It is possible to mask trial arm from cause
      of death reviewers, by using their feedback to standardise the information
      submitted to them. TRIAL REGISTRATION: ISRCTN92187251.

PMID- 25613471
TI  - [Annular keratic precipitates].

PMID- 25613472
TI  - Temperature-induced amorphisation of hexagonal ice.
AB  - We systematically studied the competition between polymorphic transformations and
      amorphisation of hexagonal ice on isobaric heating from 77 K to 155-170 K at
      pressures between 0.50 and 1.00 GPa. This competition is analysed here
      systematically by in situ dilatometry and ex situ X-ray diffraction and
      calorimetry. Volume vs. temperature curves were analysed using a novel fitting
      approach in order to understand the underlying mechanism. Hexagonal ice undergoes
      solid-state-transformation to ice IX/III at 0.50 and 0.60 GPa and to a mixture of
      ices IX/III and IV at 0.70 and 0.80 GPa. Possibly a tiny fraction of amorphous
      intermediate is transiently formed in this pressure range. At 0.85 GPa the
      amorphisation process becomes competitive, and leads to very high-density
      amorphous ice (VHDA) as by-product. At 0.90 and 0.95 GPa VHDA is the main product
      and at 1.00 GPa only VHDA is found. This represents the first observation of
      temperature-induced amorphisation (TIA) for hexagonal ice using diffraction
      methods. Our analysis suggests TIA to be a first-order phase transition which, by
      contrast to pressure-induced amorphisation (PIA), does not involve a precursor
      process. We suggest interpreting TIA as thermodynamic melting of ice followed by
      immediate vitrification rather than as mechanical collapse of hexagonal ice. The
      activation energies for amorphisation and polymorphic transformation are equal at
      ~0.75 GPa. At 1.00 GPa the activation energy for amorphisation of hexagonal ice
      is lower by about 6 kJ mol(-1) than the activation energy for polymorphic
      transitions. 

PMID- 25613473
TI  - Cell salvage in emergency trauma surgery.
AB  - BACKGROUND: Trauma is the leading cause of death in people under the age of 45
      years. Over the past 20 years, intraoperative autologous transfusions (obtained
      by cell salvage, also known as intraoperative blood salvage (IBS)) have been used
      as an alternative to blood products from other individuals during surgery because
      of the risk of transfusion-related infections such as hepatitis and human
      immunodeficiency virus (HIV). In this review, we sought to assess the effects and
      cost of cell salvage in individuals undergoing abdominal or thoracic surgery.
      OBJECTIVES: To compare the effect and cost of cell salvage with those of standard
      care in individuals undergoing abdominal or thoracic trauma surgery. SEARCH
      METHODS: We ran the search on 25 November 2014. We searched the Cochrane Injuries
      Group's Specialised Register, Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE In-Process & Other
      Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, EMBASE Classic +
      EMBASE (OvidSP), PubMed, and ISI Web of Science (SCI-Expanded & CPSI-SSH). We
      also screened reference lists and contacted principal investigators. SELECTION
      CRITERIA: Randomised controlled trials comparing cell salvage with no cell
      salvage (standard care) in individuals undergoing abdominal or thoracic trauma
      surgery. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data
      from the trial reports. We used the standard methodological procedures expected
      by The Cochrane Collaboration. MAIN RESULTS: Only one small study (n = 44)
      fulfilled the inclusion criteria. Results suggested that cell salvage did not
      affect mortality overall (death rates were 67% (14/21 participants) in the cell
      salvage group and 65% (15/23) in the control group) (odds ratio (OR) 1.07, 95%
      confidence interval (CI) 0.31 to 3.72). For individuals with abdominal injury,
      mortality was also similar in both groups (OR 0.48, 95% CI 0.11 to 2.10).Less
      donor blood was needed for transfusion within the first 24 hours postinjury in
      the cell salvage group compared with the control group (mean difference (MD) 
      4.70 units, 95% CI -8.09 to -1.31). Adverse events, notably postoperative sepsis,
      did not differ between groups (OR 0.54, 95% CI 0.11 to 2.55). Cost did not
      notably differ between groups (MD -177.81, 95% CI -452.85 to 97.23, measured in
      GBP in 2002). AUTHORS' CONCLUSIONS: Evidence for the use of cell salvage in
      individuals undergoing abdominal or thoracic trauma surgery remains equivocal.
      Large, multicentre, methodologically rigorous trials are needed to assess the
      relative efficacy, safety and cost-effectiveness of cell salvage in different
      surgical procedures in the emergency context.

PMID- 25613475
TI  - Histogram-based quantitative evaluation of endobronchial ultrasonography images
      of peripheral pulmonary lesion.
AB  - BACKGROUND: Endobronchial ultrasonography using a guide sheath (EBUS-GS) is an
      increasingly common bronchoscopic technique, but currently, no methods have been
      established to quantitatively evaluate EBUS images of peripheral pulmonary
      lesions. OBJECTIVES: The purpose of this study was to evaluate whether histogram
      data collected from EBUS-GS images can contribute to the diagnosis of lung
      cancer. METHODS: Histogram-based analyses focusing on the brightness of EBUS
      images were retrospectively conducted: 60 patients (38 lung cancer; 22
      inflammatory diseases), with clear EBUS images were included. For each patient, a
      400-pixel region of interest was selected, typically located at a 3- to 5-mm
      radius from the probe, from recorded EBUS images during bronchoscopy. Histogram
      height, width, height/width ratio, standard deviation, kurtosis and skewness were
      investigated as diagnostic indicators. RESULTS: Median histogram height, width,
      height/width ratio and standard deviation were significantly different between
      lung cancer and benign lesions (all p < 0.01). With a cutoff value for standard
      deviation of 10.5, lung cancer could be diagnosed with an accuracy of 81.7%.
      Other characteristics investigated were inferior when compared to histogram
      standard deviation. CONCLUSIONS: Histogram standard deviation appears to be the
      most useful characteristic for diagnosing lung cancer using EBUS images.

PMID- 25613476
TI  - Trypanosoma from rodents as potential source of infection in human-shaped
      landscapes of South-East Asia.
AB  - Reports of atypical human cases of Trypanosoma lewisi or T. lewisi-like and
      Trypanosoma evansi infections have increased in South-East Asia, urging to
      investigate the possible links between humans, animal reservoirs and habitats. We
      tested how habitat structure affects the infection by Trypanosoma species of
      common murine rodents, inhabiting human-dominated landscapes in South East Asia.
      For this, we used geo-referenced data of rodents investigated for Trypanosoma
      infection and land cover maps produced for seven study sites in Thailand,
      Cambodia and Lao PDR. High prevalence of infection by T. lewisi was observed in
      rodents living near human settlement and in areas with high cover of built-up
      habitat, while the infection of rodents by T. evansi was explained by increased
      landscape patchiness and high cover of rain-fed agriculture lands. These results
      suggest a likely role of wild rodents as reservoir and possible source of
      atypical human infection by animal trypanosomes. 

PMID- 25613477
TI  - Fine structure and cellular responses at the host-parasite interface in a range
      of fish-helminth systems.
AB  - A series of ultrastructural-based studies were conducted on the interface region
      in different fish-helminth systems: (a) an intestinal infection of the cestode
      Monobothrium wageneri in tench, Tinca tinca; (b) an extensive intestinal
      submucosa and mucosal infection in tench by metacercariae of an unidentified
      digenean trematode; (c) an intestinal infection in brown trout, Salmo trutta, by
      the acanthocephalan Dentitruncus truttae; (d) an extraintestinal infection by
      larvae of the acanthocephalan, Pomphorhynchus laevis in three-spined
      sticklebacks, Gasterosteus aculeatus; and (e) an infection in the livers of
      Eurasian minnow, Phoxinus phoxinus, by larvae of the nematode Raphidascaris acus.
      Endoparasitic helminths frequently cause inflammation of the digestive tract and
      associated organs, inducing the recruitment of various immune cells to the site
      of infection. In each of the fish-helminth systems that were studied, a massive
      hyperplastic granulocyte response involving mast cells (MCs) and neutrophils in
      close proximity to the helminths was documented. The current study presents data
      on the interface region in each fish-helminth system and documents the
      penetration of mast cells granules within the tegument of P. laevis larvae. No
      extracellular vesicles containing tegumental secretions from any of the four
      different taxa of endoparasitic helminths species at the host-parasite interface
      region were seen. 

PMID- 25613478
TI  - Gene expression profile in the early stage of angiotensin II-induced cardiac
      remodeling: a time series microarray study in a mouse model.
AB  - BACKGROUND/AIMS: Angiotensin II (Ang II) plays a critical role in the cardiac
      remodeling contributing to heart failure. However, the gene expression profiles
      induced by Ang II in the early stage of cardiac remodeling remain unknown.
      METHODS: Wild-type male mice (C57BL/6 background, 10-weeek-old) were infused with
      Ang II (1500 ng/kg/min) for 7 days. Blood pressure was measured. Cardiac function
      and remodeling were examined by echocardiography, H&E and Masson staining. The
      time series microarrays were then conducted to detected gene expression profiles.
      RESULTS: Microarray results identified that 1,489 genes were differentially
      expressed in the hearts at day 1, 3 and 7 of Ang II injection. These genes were
      further classified into 26 profiles by hierarchical cluster analysis. Of them, 4
      profiles were significant (No. 19, 8, 21 and 22) and contained 904 genes. Gene
      Ontology showed that these genes mainly participate in metabolic process,
      oxidation-reduction process, extracellular matrix organization, apoptotic
      process, immune response, and others. Significant pathways included focal
      adhesion, ECM-receptor interaction, cytokine-cytokine receptor interaction, MAPK
      and insulin signaling pathways, which were known to play important roles in Ang
      II-induced cardiac remodeling. Moreover, gene co-expression networks analysis
      suggested that serine/cysteine peptidase inhibitor, member 1 (Serpine1, also
      known as PAI-1) localized in the core of the network. CONCLUSIONS: Our results
      indicate that many genes are mainly involved in metabolism, inflammation, cardiac
      fibrosis and hypertrophy. Serpine1 may play a central role in the development of
      Ang II-induced cardiac remodeling at the early stage.

PMID- 25613479
TI  - Photocatalytic carbon dioxide reduction with rhodium-based catalysts in solution
      and heterogenized within metal-organic frameworks.
AB  - The first photosensitization of a rhodium-based catalytic system for CO2
      reduction is reported, with formate as the sole carbon-containing product.
      Formate has wide industrial applications and is seen as valuable within fuel cell
      technologies as well as an interesting H2 -storage compound. Heterogenization of
      molecular rhodium catalysts is accomplished via the synthesis, post-synthetic
      linker exchange, and characterization of a new metal-organic framework (MOF)
      Cp*Rh@UiO-67. While the catalytic activities of the homogeneous and heterogeneous
      systems are found to be comparable, the MOF-based system is more stable and
      selective. Furthermore it can be recycled without loss of activity. For formate
      production, an optimal catalyst loading of ~10 % molar Rh incorporation is
      determined. Increased incorporation of rhodium catalyst favors thermal
      decomposition of formate into H2 . There is no precedent for a MOF catalyzing the
      latter reaction so far. 

PMID- 25613480
TI  - MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1.
AB  - MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis
      and tumor progression. In this study, we investigate whether let-7b acts as a
      tumor suppressor to inhibit invasion and metastasis in gastric cancers. We
      analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and
      adjacent non-neoplastic tissues by quantitative real-time polymerase chain
      reaction. Functional analysis of let-7b expression was assessed in vitro in
      gastric cancer cell lines with let-7b precursor and inhibitor. The roles of let
      7b in tumorigenesis and tumor metastasis were analyzed using a stable let-7b
      expression plasmid in nude mice. A luciferase reporter assay was used to assess
      the effect of let-7b on inhibitor of growth family, member 1 (ING1) expression.
      Real-time PCR showed decreased levels of let-7b expression in metastatic gastric
      cancer tissues and cell lines that are potentially highly metastatic. Cell
      invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell
      lines after transfection with let-7b mimics. Nude mice with xenograft models of
      gastric cancer confirmed that let-7b could inhibit gastric cancer metastasis in
      vivo after transfection by the lentivirus pGCsil-GFP- let-7b. Luciferase reporter
      assays demonstrated that let-7b directly binds to the 3'-UTR of ING1, and real
      time PCR and western blotting further indicated that let-7b downregulated the
      expression of ING1 at the mRNA and protein levels. Our study demonstrates that
      overexpression of let-7b in gastric cancer can inhibit invasion and migration of
      gastric cancer cells through directly targeting the tumor metastasis-associated
      gene ING1. These findings help clarify the molecular mechanisms involved in
      gastric cancer metastasis and indicate that let-7b modulation may be a bona fide
      treatment of gastric cancer. 

PMID- 25613481
TI  - Tomato thymidine kinase-based suicide gene therapy for malignant glioma--an
      alternative for Herpes Simplex virus-1 thymidine kinase.
AB  - Malignant gliomas (MGs) are the most common malignant primary brain tumors with a
      short life estimate accompanied by a marked reduction in the quality of life.
      Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the
      best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV
      and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK
      (ToTK) has shown high activity in combination with its specific substrate
      azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT
      could be used as an alternative to HSV-TK/GCV therapy. Both treatments
      demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments
      decreased tumor growth and tumors were smaller in comparison with controls in
      mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly
      increased compared with control mice (*P<0.05) but not as compared with HSV
      TK/GCV-treated mice. No significant differences were observed in clinical
      chemistry safety analyses. We conclude that both treatments showed a beneficial
      treatment response in comparison to controls on tumor growth and ToTK/AZT also on
      survival. There were no significant differences between these treatments.
      Therefore ToTK/AZT could be considered as an alternative treatment option for MG
      because of its favorable therapeutic characteristics. 

PMID- 25613482
TI  - HER-2-induced PI3K signaling pathway was involved in the pathogenesis of gastric
      cancer.
AB  - Human epidermal growth factor receptor-2 (HER-2) overexpression was closely
      associated with the tumor growth and invasion, we here aimed to investigate the
      mechanism of HER-2 mediation in the pathogenesis of gastric cancer (GC). We first
      detected the expression of HER-2 in GC cell line SGC-7901 and then examined the
      levels of nuclear factor-kappaB (NF-kappaB), matrix metalloproteinase-9 (MMP-9)
      and intercellular adhesion molecule-1 (ICAM-1) and the association between them
      by molecular methods. Statistical analysis was used to compare the significance.
      We further detected the possible molecular mechanism involved in their
      relationship in the SGC-7901 genesis. The MMP-9, NF-kappaB and secretory type (s
      ICAM-1) levels were significantly greater in peripheral blood serum from SGC-7901
      than healthy control GES-1 (P<0.01). ICAM-1, MMP-9 and NF-kappaB mRNA and protein
      levels were more highly expressed in SGC-7901 than healthy control GES-1. The
      expression levels of NF-kappaB, MMP-9 and ICAM-1 were positively related in GC
      cell line SGC-7901, which was HER-2 positive. The HER-2 positive SGC-7901
      secreted more transforming growth factor beta 1 (TGF-beta1) and resultantly
      activated MMP-9 to enhance s-ICAM-1 secretion and further studies showed that
      phosphatidylinositol-3 kinase (PI3K)/Akt/NF-kappaB signaling pathway was involved
      in GC pathogenesis. The GC cells that express the HER-2 oncogene spur the
      activation of NF-kappaB that can upregulate the expression of ICAM-1 and induce
      the expression of MMP-9, which hydrolyzes ICAM-1 into s-ICAM-1 to promote tumor
      immune escape. TGF-beta1-induced PI3K/Akt/NF-kappaB signaling pathway was
      involved in the pathogenesis of GC and they could be a new target for cancer
      therapy. The GC cells that express the HER-2 oncogene spur the activation of NF
      kappaB that can upregulate the expression of ICAM-1 and induce the expression of
      MMP-9, which hydrolyzes ICAM-1 into s-ICAM-1 to promote tumor immune escape. TGF
      beta1-induced PI3K/Akt/NF-kappaB signaling pathway was involved in the
      pathogenesis of GC and they could be a new target for cancer therapy. 

PMID- 25613484
TI  - Associations between motor vehicle crashes and mental health problems: data from
      the National Survey of Adolescents-Replication.
AB  - Motor vehicle crashes (MVCs) are a leading cause of physical injuries and
      mortality among children and adolescents in the United States. The purpose of
      this study was to examine associations between having an MVC and mental health
      outcomes, including posttraumatic stress disorder (PTSD), depression, and drug
      and alcohol misuse in a nationally representative sample of adolescents. A sample
      of 3,604 adolescents, aged 12-17 years, was assessed as part of the 2005 National
      Survey of Adolescents-Replication (NSA-R) study. Data were weighted according to
      the 2005 U.S. Census estimates. Within this sample, 10.2% of adolescents reported
      having at least 1 serious MVC. The prevalence of current PTSD and depression
      among adolescents having an MVC was 7.4% and 11.2%, respectively. Analyses
      revealed that an MVC among adolescents aged 15 years and younger was
      independently associated with depression (OR = 2.17) and alcohol abuse (OR =
      2.36) after adjusting for other risk factors, including a history of
      interpersonal violence. Among adolescents aged 16 years and older, an MVC was
      associated only with alcohol abuse (OR = 2.08). This study was the first attempt
      to explore adverse mental health outcomes associated with MVCs beyond traumatic
      stress symptoms among adolescents in a nationally representative sample. 

PMID- 25613483
TI  - Towards a commercial process for the manufacture of genetically modified T cells
      for therapy.
AB  - The recent successes of adoptive T-cell immunotherapy for the treatment of
      hematologic malignancies have highlighted the need for manufacturing processes
      that are robust and scalable for product commercialization. Here we review some
      of the more outstanding issues surrounding commercial scale manufacturing of
      personalized-adoptive T-cell medicinal products. These include closed system
      operations, improving process robustness and simplifying work flows, reducing
      labor intensity by implementing process automation, scalability and cost, as well
      as appropriate testing and tracking of products, all while maintaining strict
      adherence to Current Good Manufacturing Practices and regulatory guidelines. A
      decentralized manufacturing model is proposed, where in the future patients'
      cells could be processed at the point-of-care in the hospital. 

PMID- 25613485
TI  - The application of NCaRBS to the Trendelenburg test and total hip arthroplasty
      outcome.
AB  - This paper compares the frontal plane hip function of subject's known to have had
      hip arthroplasty via either the lateral (LA) or posterior (PA) surgical
      approaches and a group of subjects associated with no pathology (NP). This is
      investigated through the Trendelenburg test using 3D motion analysis and
      classification. Here, a recent development on the Classification and Ranking
      Belief Simplex (CaRBS) technique, able to undertake n-state classification, so
      termed NCaRBS is employed. The relationship between post-operative hip function
      measured during a Trendelenburg Test using three patient characteristics (pelvic
      obliquity, frontal plane hip moment and frontal plane hip power) of LA, PA and NP
      subjects are modelled together. Using these characteristics, the classification
      accuracy was 93.75% for NP, 57.14% for LA, 38.46% for PA. There was a clear
      distinction between NP and post-surgical function. 3/6 LA subjects and 6/8 PA
      subjects were misclassified as having NP function, implying that greater function
      is restored following the PA to surgery. NCaRBS achieved a higher accuracy
      (65.116%) than through a linear discriminant analysis (48.837%). A Neural Network
      with two-nodes achieved the same accuracy (65.116%) and as expected was further
      improved with three-nodes (69.767%). A valuable benefit to the employment of the
      NCaRBS technique is the graphical exposition of the contribution of patient
      characteristics to the classification analysis. 

PMID- 25613486
TI  - Differential Effects of Tumor Secreted Factors on Mechanosensitivity, Capillary
      Branching, and Drug Responsiveness in PEG Hydrogels.
AB  - Solid cancers induce the formation of new blood vessels to promote growth and
      metastasis. Unlike the normal vascular networks, the tumor induced vasculatures
      exhibit abnormal shape and function. Past efforts have been focused on
      characterizing the altered growth factor signaling pathway in tumor capillary
      endothelial cells; however, the mechanical microenvironment of tumor also plays a
      significant role in regulating the formation of vascular patterns. Here, we used
      synthetic hydrogel based cell culture platforms to probe how activation of human
      umbilical endothelial cells (HUVECs) by tumor secreted factors alters the
      responses to matrix modulus and in turn the capillary network formation and drug
      sensitivity. Our study revealed that while in absence of activation, HUVECs
      prefer a substrate of appropriate stiffness for optimal capillary network
      formation; stimulation by tumor cells disrupts the mechano-responsive behavior of
      HUVECs. Additionally, the effect of vandetanib on reducing the capillary network
      was also investigated. The response of HUVECs to the anti-angiogenic agent was
      substrate modulus dependent displaying increased sensitivity on the compliant
      gels. Stimulation by tumor cells reduced the responsiveness to vandetanib,
      particularly when plated on stiffer gels. 

PMID- 25613487
TI  - Sero-conversion rate of Syphilis and HIV among pregnant women attending antenatal
      clinic in Tanzania: a need for re-screening at delivery.
AB  - BACKGROUND: Despite the available cost effective antenatal testing and treatment,
      syphilis and human immunodeficiency virus (HIV) are still among common infections
      affecting pregnant women especially in developing countries. In Tanzania,
      pregnant women are tested only once for syphilis and HIV during antenatal clinic
      (ANC) visits. Therefore, there are missed opportunities for syphilis and HIV
      screening among those who were not tested during ANC visits and those acquiring
      infections during the course of pregnancy. This study was designed to determine
      the syphilis and HIV seroprevalence at delivery and seroconversion rate among
      pregnant women delivering at Bugando Medical Centre (BMC). METHODS: A cross
      sectional, hospital-based study involving pregnant women attending Bugando
      Medical Centre (BMC) antenatal clinic was done from January to March 2012. Serum
      samples were collected and tested for HIV and syphilis using HIV and syphilis
      rapid tests. Demographic and clinical data were collected using a standardized
      data collection tool and analysed using STATA version 11. RESULTS: A total of 331
      and 408 women were screened for syphilis and HIV during antenatal respectively.
      Of 331 women who screened negative for syphilis at ANC, nine (2.7%) were
      seropositive at delivery while of 391who tested negative for HIV during ANC eight
      (2%) were found to be positive at delivery. Six (1.8%) and 23 (9%) of women who
      did not screen for syphilis and HIV at ANC were seropositive for syphilis and HIV
      at delivery respectively. There was significant difference of seroprevalence for
      HIV, among women who tested negative at ANC and those who did not test at ANC (2%
      vs.9%, P,<0.001). The overall prevalence of syphilis and HIV at delivery was 15
      (2.3%) and 48 (7.2%) respectively. Syphilis seropositivity at delivery was
      significantly associated with HIV co-infection (p < 0.001), male partner
      circumcision (p = 0.011) and alcohol use among women (p < 0.001). CONCLUSIONS:
      The current protocol of screening for syphilis and HIV only once during pregnancy
      as practiced in Tanzania may miss women who get re-infected and seroconvert
      during pregnancy. Re-screening for syphilis and HIV during the course of
      pregnancy and at delivery is recommended in Tanzania as it can help to identify
      such women and institute appropriate treatment.

PMID- 25613488
TI  - Effect of microparticulate silver addition in dental adhesives on secondary
      caries in vitro.
AB  - OBJECTIVES: The aim of the present study was evaluate the effect of
      microparticulate silver additions in adhesives on secondary caries formation
      using an artificial mouth model. MATERIALS AND METHODS: One hundred eight intact
      human third molars received standardized Class-V resin composite restorations
      (Filtek Supreme XTE bonded with Syntac, Scotchbond 1 XT, Futurabond M). Adhesives
      were charged with different amounts of microparticulate silver (0 %/0.1 %/0.5 %).
      After storage for 4 weeks at 37  degrees C, teeth were subjected to 10,000
      thermocycles (+5  degrees C and +55  degrees C), and impressions were taken.
      Streptococcus mutans 10449 was used in a nutrition medium for secondary caries
      simulation in a fully automated artificial mouth. After completion of
      thermocycling and biological load cycling, impressions were taken and replicas
      were investigated under a light microscope for gap widths at enamel and dentin
      margins. Evaluation of fluorescence was carried out using a special FITC filter.
      The demineralization depths at the cavity margin were evaluated using Xpert for
      Windows working at a pixel distance of 5 MUm. RESULTS: After thermocycling, no
      difference in gap widths and demineralization depths was found (p > 0.05). After
      incubation, gap widths and demineralization depths were significantly reduced
      with higher amounts of silver loading in most of the adhesives (p < 0.05). The
      0.5 % silver addition resulted in a slight decrease of secondary caries at resin
      dentin margins (p < 0.05). CONCLUSIONS: Addition of microparticulate silver in
      commercially available dental adhesives has the potential of reducing secondary
      caries. CLINICAL RELEVANCE: The chosen setup was able to produce secondary caries
      with a distinct in vivo appearance. Microparticulate silver additions in dental
      adhesives may have an impact on inhibition of secondary caries.

PMID- 25613489
TI  - Glanzmann's thrombasthenia: a rare case of spontaneous bilateral hemotympanum.

PMID- 25613492
TI  - Corrigendum.

PMID- 25613490
TI  - Dysbiosis of fungal microbiota in the intestinal mucosa of patients with
      colorectal adenomas.
AB  - The fungal microbiota is an important component of the human gut microbiome and
      may be linked to gastrointestinal disease. In this study, the fungal microbiota
      of biopsy samples from adenomas and adjacent tissues was characterized by deep
      sequencing. Ascomycota, Glomeromycota and Basidiomycota were identified as the
      dominant phyla in both adenomas and adjacent tissues from all subjects. Among the
      60 genera identified, the opportunist pathogens Phoma and Candida represented an
      average of 45% of the fungal microbiota. When analyzed at the operational
      taxonomic unit (OTU) level, however, a decreased diversity in adenomas was
      observed, and three OTUs differed significantly from the adjacent tissues.
      Principal Component Analysis (PCA) revealed that the core OTUs formed separate
      clusters for advanced and non-advanced adenomas for which the abundance of four
      OTUs differed significantly. Moreover, the size of adenomas and the disease stage
      were closely related to changes in the fungal microbiota in subjects with
      adenomas. This study characterized the fungal microbiota profile of subjects with
      adenomas and identified potential diagnostic biomarkers closely related to
      different stages of adenomas. 

PMID- 25613493
TI  - Extraction parameters for metabolomics from cultured cells.
AB  - The successful extraction of metabolites is a critical step in metabolite
      profiling. By optimizing metabolite extraction, the range and quantitative
      capacity of metabolomics studies can be improved. We considered eight separate
      extraction protocols for the preparation of a metabolite extract from cultured
      mammalian cells. Parameters considered included temperature, pH, and cell washing
      before extraction. The effects on metabolite recovery were studied using a liquid
      chromatography high-resolution mass spectrometry (LC-HRMS) platform that measures
      metabolites of diverse chemical classes, including amino acids, lipids, and sugar
      derivatives. The temperature considered during the extraction or the presence of
      formic acid, a commonly used additive, was shown to have minimal effects on the
      measured ion intensities of metabolites. However, washing of samples before
      metabolite extraction, whether with water or phosphate-buffered saline, exhibited
      dramatic effects on measured intensities of both intracellular and extracellular
      metabolites. Together, these findings present a systematic assessment of
      extraction conditions for metabolite profiling. 

PMID- 25613494
TI  - Splenic vessel preservation versus Warshaw's technique during spleen-preserving
      distal pancreatectomy: a meta-analysis and systematic review.
AB  - BACKGROUND: Splenic preservation can be achieved through splenic vessel resection
      by Warshaw's technique (WT) or by preserving the splenic vessels. This meta
      analysis aims to provide evidence-based comparison regarding the perioperative
      outcome and long-term benefits between patients with and without splenic vessel
      preservation (SVP) during spleen-preserving distal pancreatectomy. METHOD: A meta
      analysis was performed to evaluate studies comparing splenic vessel preservation
      versus resection groups. Ten retrospective studies including 699 patients were
      eligible for an analysis of general, perioperative, and long-term outcomes. A
      further analysis composed of five subgroups was also conducted in terms of
      laparoscopic approach. RESULTS: Warshaw's technique related to significant
      shorter operation time (P < 0.0001). There was no difference in blood loss (P =
      0.45) as well as median tumor size (p = 0.1) between the two groups. The overall
      rate of complications indicated no difference between SVP and WT (P = 0.1),
      including pancreatic fistula rates, which were not statistically different among
      the treatment groups (P = 0.27). However, the occurrence of gastric varices and
      splenic infarction was significant higher in the WT group (P < 0.01). In
      laparoscopic subgroups, patients treated by WT had much lower blood loss (P =
      0.002). CONCLUSION: In spleen-preserving distal pancreatectomy, comparing with
      SVP, there is no evidence of significant benefit of WT. Nonetheless, surgeons
      should master both techniques and choose an appropriate one based on personal
      experience and a "case by case" situation. However, the current available
      evidence is weak, and further randomized controlled data are warranted.

PMID- 25613495
TI  - Quantitative determination of three pentacyclic triterpenes from five Swertia L.
      species endemic to Western Ghats, India, using RP-HPLC analysis.
AB  - Aim of this study was to identify pentacyclic triterpenoids betulinic acid (BA),
      oleanolic acid (OA) and ursolic acid (UA) from five Swertia species endemic to
      Western Ghats, which are used as substitutes as well as adulterants to Swertia
      chirayita. Our results indicate that the concentration of active compound vary
      largely among and within the species from different localities. OA was found in a
      higher amount in all species compared to BA and UA. From the results, it was
      clear that BA, OA and UA are present in the endemic species collected from
      Western Ghats, thus advocating the use of these species as alternate sources to
      S. chirayita. This in due course may release pressure of exploitation from
      natural resources of S. chirayita and help to bring it out from an endangered
      category from conservation point of view. 

PMID- 25613497
TI  - Preconditioning by oxygen-glucose deprivation preserves cell proliferation and
      reduces cytotoxicity in primary astrocyte cultures.
AB  - Hypoxic-ischemic preconditioning (HIPC) has a neuroprotective effect against a
      subsequent, more severe perinatal hypoxic-ischemic episode. The protective
      processes of preconditioning (PC) in the immature brain remain undefined but are
      most likely related to the immune cells of the central nervous system. To
      determine the role of astrocytes in HIPC, we initially exposed primary rat
      astrocytes to oxygen-glucose deprivation (OGD) for 30 minutes as a PC stimulus. A
      subsequent more severe insult was induced 24 hours later by exposing the
      astrocytes to OGD for 3 hours. These experiments revealed that OGD for 3 hours
      induced increased cytotoxicity as measured by lactate dehydrogenase in primary
      astrocytes, which was diminished in astrocytes earlier subjected to PC. Moreover,
      decreased cell proliferation, as measured by Ki67, and lower cytokine expression
      (IL-1beta, TNF-alpha, IL-6, IL-10) were observed in astrocytes subjected to OGD
      for 3 hours, while these levels remained unchanged in PC+OGD cells. Therefore, we
      speculate that PC by OGD may affect the survival, proliferation and function of
      primary cultured astrocytes which may partly explain the neuroprotective
      properties of HIPC seen in HI rat models.

PMID- 25613496
TI  - Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and
      metastasis in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has
      been demonstrated to be an important player in various human malignancies; it is
      thought to promote tumor growth by cell cycle regulating. However, the roles of
      MALAT1 in esophageal squamous cell carcinoma(ESCC), and the mechanisms involved
      in cell cycle regulation remain poorly understood. Moreover, the factors
      contributing to its up-regulation in tumor tissues are still largely unclear.
      METHODS: Expression of MALAT1 was determined from cell lines and clinical samples
      by qRT-PCR. The effects of MALAT1 knockdown on cell proliferation, cell cycle,
      apoptosis, migration, and invasion were evaluated by in vitro and in vivo assays.
      The potential protein expression changes were investigated by Western-blotting.
      The methylation status of the CpG island in the MALAT1 promoter was explored by
      bisulfite sequencing, while the copy numbers in tumor tissues and blood samples
      were detected by a well-established AccuCopy(TM) method. RESULTS: MALAT1 was over
      expressed in 46.3% of ESCC tissues, mostly in the high-stage tumor samples.
      Enhanced MALAT1 expression levels were positively correlated with clinical
      stages, primary tumor size, and lymph node metastasis. Inhibition of MALAT1
      suppressed tumor proliferation in vitro and in vivo, as well as the migratory and
      invasive capacity. MALAT1 depletion also induced G2/M phase arrest and increased
      the percentage of apoptotic cells. Western-blotting results implicated that the
      ATM-CHK2 pathway which is associated with G2/M arrest was phosphorylated by
      MALAT1 knockdown. No effects of CpG island methylation status on MALAT1
      expression were found, whereas amplification of MALAT1 was found in 22.2% of
      tumor tissues, which correlated significantly with its over-expression. However,
      neither association between tissue copy number amplification and germline copy
      number variation, nor correlation between germline copy number variation and ESCC
      risk were identified in the case-control study. CONCLUSIONS: Our data suggest
      that MALAT1 serves as an oncogene in ESCC, and it regulates ESCC growth by
      modifying the ATM-CHK2 pathway. Moreover, amplification of MALAT1 in tumor
      tissues may play an important role for its up-regulation, and it seems that the
      gene amplification in tumor tissues emerges during ESCC progression, but is not
      derived from germline origins.

PMID- 25613498
TI  - Lipopolysaccharide-induced chorioamnionitis causes acute inflammatory changes in
      the ovine central nervous system.
AB  - OBJECTIVE: To better understand the inflammatory response in the central nervous
      system (CNS) after lipopolysaccharide (LPS)-induced chorioamnionitis. STUDY
      DESIGN: Fetal sheep were exposed to intra-amniotic LPS 2 or 14 days before
      preterm delivery at 125 days of gestation. mRNA levels of cytokines, TLRs and
      anti-oxidants were determined in different CNS regions. RESULTS: Interleukin
      1beta levels increased in hippocampus, cortex and cerebellum 2 days after LPS
      exposure, while Interleukin 8 levels increased in the periventricular white
      matter as well. Levels returned back to control levels after 14 days. Tumor
      necrosis factor-alpha levels increased in hippocampus and cortex after 2 days.
      Toll like receptor 4 levels was upregulated in all grey matter regions 2 and 14
      days after exposure. Glutathione s-transferase mRNA levels were lower after 2 and
      14 days in all grey matter regions. CONCLUSION: Intra-amniotic LPS exposure
      causes acute and region-specific changes in inflammatory markers in the fetal
      brain, with grey matter being more affected than white matter. CONDENSATION:
      Intra-amniotic LPS exposure causes acute and region-specific changes in
      cytokines, TLR and anti-oxidants levels, with grey matter being more affected
      than white matter.

PMID- 25613499
TI  - TDP-43 as a Modulator of Synaptic Plasticity in a Mouse Model of Spinal
      Motoneuron Degeneration.
AB  - Transactive response DNA-binding protein of 43 kDa (TDP-43) is a nuclear DNA/RNA
      binding protein involved in gene transcription and mRNA processing. Recently, TDP
      43 has been found in the cytoplasmic inclusions observed in amyotrophic lateral
      sclerosis. Substantial attention has been devoted to the toxic effects of the
      cytoplasmic TDP-43 aggregates, whereas the functional role of this protein
      remains poorly investigated. Interestingly, TDP-43 could be localized in the
      synapse and affect synaptic plasticity and locomotion in Drosophila. Here, we
      would like to understand if TDP-43 could modulate spinal cord plasticity in a
      mouse model of neurotoxic motoneuron depletion. Therefore, the expression levels
      of TDP- 43 and synaptic proteins such as synapsin-I and the alpha-amino-3-hydroxy
      5-methyl-4- isoxazolepropionate (AMPA) receptor subunits GluR1, GluR2 and GluR4
      were measured by western blotting. By using multivariate regression models,
      protein expression levels were correlated each other as well as with the motor
      performance. The results suggested that motor performance could be linked to the
      expression of synapsin-I, and that the latter could depend on TDP-43, which in
      turn could interact with AMPA receptors. In conclusion, our results suggest that
      TDP-43 is likely involved in the modulation of synaptic plasticity. Given the
      increasing interest in mouse models of TDP-43 gain or loss of function in
      neurodegenerative diseases, the elucidation of the role of TDP-43 in the spinal
      cord is mandatory. More generally, given the recently increased knowledge about
      spinal cord plasticity, we postulate that the stimulation of the intrinsic
      plastic potential of spinal cord would be a successful repairing strategy.

PMID- 25613500
TI  - Biochemical Markers for Brain Injury Monitoring in Children with or without
      Congenital Heart Diseases.
AB  - Perinatal asphyxia (PA) still constitutes a common complication involving a large
      number of infants with or without congenital heart diseases (CHD). PA affects 0.2
      0.6% of full-term neonates, 20% of which suffer mortal hypoxic-ischemic
      encephalopathy, and among survivors 25% exhibit permanent consequences at
      neuropsychological level. Each year, about one third of 1000 live births
      underwent to surgical intervention in early infancy and/or are at risk for
      ominous outcome. Advances in brain monitoring, in anesthetic and cardiothoracic
      surgical techniques, including selective or total body cooling, cardiopulmonary
      bypass (CPB) and deep hypothermic circulatory arrest, have essentially reduced
      mortality expanding the possibility to address functional neurologic and cardiac
      outcomes in long-term survivors. However, open-heart surgery constitutes a time
      frame of planned ischemia-reperfusion injury, which is a price to pay in the
      treatment or palliation of CHD. Infants who underwent heart surgery and non-CHD
      infants complicated by PA share similarities in their neurodevelopmental profile
      and a common form of brain damage due to hypoxic-ischemic injury. The purpose of
      the present review was to evaluate different mechanisms implicated in brain
      injury following CPB and PA and how it is possible to monitor such injury by
      means of available biomarkers (S100B protein, Activin A, Adrenomedullin).

PMID- 25613501
TI  - Antenatal Maternal Antidepressants Drugs Affect S100B Concentrations in Fetal
      Maternal Biological Fluids.
AB  - INTRODUCTION: Antidepressant treatment during pregnancy is speedily increasing in
      developed countries and this phenomenon has occurred without firm evidence on
      safety and/or efficacy. AIMS: The present study investigated from mid-trimester
      of pregnancy up to 24 hours after birth the pattern of a brain damage marker,
      namely S100B, in maternal fetal and neonatal biological fluids of pregnant women
      and their newborns antenatally treated by antidepressant drugs such as selective
      serotonin re-uptake inhibitors (SSRI). METHODS: we conducted an observational
      study on 75 pregnant women treated in the mid -third trimester by antidepressant
      drugs and 231 healthy pregnancies. S100B concentrations were measured at 7
      predetermined monitoring time-points before, during and after treatment in
      maternal, fetal and neonatal biological fluids and correlated with neurological
      follow-up at 7 days from birth. RESULTS: In SSRI group S100B concentrations were
      significantly higher in SSRI than controls (P<0.001, for all) in maternal blood,
      in amniotic fluid, in arterial and venous cord blood and at 24-h from birth.
      Highest (P<0.05) S100B levels were found in SSRI infants showing major
      neurological symptoms at 7-d follow-up. CONCLUSION: The present data on increased
      S100B levels in maternal, fetal and neonatal biological fluids suggest that SSRI
      administration although beneficial to the mother, presents some risks for the
      infant.

PMID- 25613502
TI  - Neuroprotective effects of a glutathione depletor in rat post-ischemic
      reperfusion brain damage.
AB  - The induction of heme oxygenase (HO), the rate-limiting enzyme in heme
      degradation, occurs as an adaptative response to oxidative stress and is
      consequent to decrease in cellular glutathione levels. Our previous studies
      demonstrated significant increase in survival rates of rats treated with
      glutathione depletors and submitted to transient cerebral ischemia. The aim of
      the present research was to test the effects of L-Buthionine sulfoximine (BSO), a
      glutathione depletor, during cerebral post-ischemic reperfusion. Cerebral
      ischemia was induced by bilateral clamping of common carotid arteries for 20 min.
      Each sample was used for glutathione ad lipid peroxidation level dosage and for
      evaluating the expression of heme oxygenase both after a single subcutaneous
      administration of BSO and without treatment. In the same experimental conditions,
      endothelial, inducible and neuronal Nitric Oxide Synthase (eNOS, iNOS and nNOS)
      and Dimethylarginine Dimethyl amine Hydrolases (DDAH-1 and DDAH-2) were also
      evaluated. Results obtained in the present study suggested that HO-1 over
      expression may be implicated in the protective effect of BSO in post-ischemic
      reperfusion brain damage, although the involvement of other important stress
      mediators cannot be ruled out.

PMID- 25613503
TI  - Fetal asphyctic preconditioning protects against perinatal asphyxia- induced
      apoptosis and astrogliosis in neonatal brain.
AB  - Hypoxic-ischemic preconditioning is an endogenous mechanism in which exposure to
      a sublethal episode of hypoxia-ischemia protects against a subsequent more severe
      episode. Although several postnatal models of hypoxic-ischemic preconditioning
      have been established, hardly any perinatal models exist. Therefore, the
      objective of this study is to validate a new rodent model. We investigate whether
      mild fetal asphyxia (FA) as a preconditioning stimulus, protects against severe
      perinatal asphyxia (PA) when looking at neonatal brain histology. FA was induced
      at embryonic day 17 (E17) by temporarily clamping the uterine circulation. A
      caesarean section was performed at E21/22 and PA was induced by submersing the
      uterine horns, still containing the fetuses, in a water bath. Brains were
      examined for histological changes at either postnatal day 7 or 14. We used
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      staining to detect apoptotic cell death and a glial fibrillary acidic protein
      (GFAP) staining to detect reactive astrocytes. Interestingly, the preconditioned
      group showed significantly less perinatal mortality than non-preconditioned
      groups. Furthermore, preconditioned animals had significantly less TUNEL-positive
      cells and less GFAP-positive cells in striatum, prefrontal cortex and hippocampus
      compared to the non-preconditioned animals that underwent PA. Consequently, mild
      FA might cause neuroprotection by inducing anti-apoptotic mechanisms and
      attenuating astrogliosis. Considering the morphological findings in the neonatal
      brain from this study, together with previously reported long-term behavioral
      outcomes in this model, we can conclude that this is a suitable experimental
      model to investigate mechanisms of endogenous neuroprotection in the fetal brain.
      Identifying these endogenous neuroprotective mechanisms will provide novel
      potential targets for future pharmacological intervention in asphyctic newborns.

PMID- 25613504
TI  - Tissue transglutaminase expression during neural differentiation of human
      mesenchymal stem cells.
AB  - Herein, we assessed the expression of transglutaminase-2 (TG2) during in vitro
      neural differentiation of human Mesenchymal Stem Cells (hMSCs) induced by some
      Growth Factors (GFs). The amount and distribution of mRNAs for some
      transglutaminase (TGs) isoforms (TG1, TG2, TG3, TG5) were also evaluated. In
      addition, we tested some neural lineage markers (Glial Acid Fibrillary Protein,
      GFAP; Neurofilament Protein, NF; Nestin; beta-Tubulin III). A progressive
      increase of all neural markers during GFs neural differentiation of hMSCs was
      found. A significant overexpression of TG1 and TG2 mRNA was observed in
      undifferentiated hMSCs. GFs-treatment induced a progressive decrease of TG1 mRNA
      during hMSCs differentiation. A significant down-regulation of TG2 mRNA in 2 days
      in vitro (DIV) GFs-treated cells was observed. TG2 mRNA progressively increased
      during GFs hMSCs differentiation, reaching after 6 DIV of GFs-treatment of
      similar values to those observed in undifferentiated cells. TG3 mRNA levels were
      express at very low only in undifferentiated hMSCs, whereas TG5 mRNA was
      undetectable in undifferentiated and differentiated hMSCs. Immunocytochemical and
      Western blot analysis showed an overexpression of TG2 in undifferentiated hMSCs.
      A dramatic reduction of the protein levels in 2 DIV GFs-treated cells was
      observed. Its expression levels progressively increased during the
      differentiation of hMSCs with GFs, reaching after 6 DIV of the treatment similar
      values to those observed in undifferentiated cells. Our findings demonstrate the
      presence of multiple TGs in hMSCs during neural differentiation in vitro induced
      by GFs, and suggest that TG2 may be part of the downstream events associated to
      neural differentiation.

PMID- 25613505
TI  - Silymarin extends lifespan and reduces proteotoxicity in C. elegans Alzheimer's
      model.
AB  - Aging is a process of progressive decline in physiological functions resulting in
      increased vulnerability to diseases and death. Aging results in increased rates
      of age related disorders like neurodegenerative diseases, cardiovascular
      diseases, diabetes, cancer, arthritis etc. Modulation of insulin signaling,
      protein aggregation, stress, free radical damage and inflammation are the major
      causes for deleterious changes resulting in aging. Many studies are being
      undertaken to find novel compounds which can improve a typical human life span
      and aid in healthy aging. We investigated the potential of one such compound
      silymarin for its anti-aging effect. Silymarin is a flavanone derivative
      extracted from the seeds of the milk thistle Silybum marianum. It is widely used
      for the treatment of liver diseases in clinical practice. We tested the anti
      aging efficacy of silymarin using the Caenorhabditis elegans model system. Our
      results demonstrate that C. elegans treated with 25MUM and 50MUM silymarin
      concentration resulted in an increase in mean lifespan by 10.1% and 24.8%
      respectively compared to untreated control. Besides increased lifespan, silymarin
      treated aged animals showed better locomotion rate, higher response to stimuli
      and improved tolerance to stress compared to untreated control. We also checked
      the potential of silymarin to slow the progression of neurodegenerative disorder
      like Alzheimer's disease (AD) by using CL4176 C. elegans model for AD. C. elegans
      CL4176 transgenic animal induces expression of amyloid beta-protein (Abeta1-42)
      in muscle tissues when subjected to temperature of 23 degrees C and above
      resulting in worm paralysis. CL4176 animals treated with silymarin showed delayed
      paralysis via enhancing resistance to oxidative stress. These results suggested
      that silymarin is a potential hormetin for preventing aging and age-related
      diseases. 

PMID- 25613507
TI  - The blood-brain barrier in multiple sclerosis: microRNAs as key regulators.
AB  - Multiple sclerosis (MS) is a progressive inflammatory disease of the central
      nervous system (CNS) leading to severe neurological deficits. To date, no
      treatment is available that halts disease progression, but clinical symptoms can
      be generally improved by therapies involving anti-inflammatory and/or immune
      modulatory reagents, which may cause off-target effects. Therefore, there remains
      a high and unmet need for more selective treatment strategies in MS. An early
      event in MS is a diminished function of the blood-brain barrier (BBB) which
      consists of specialized brain endothelial cells (BECs) that are supported in
      their barrier function by surrounding glial cells. Leakage and inflammation of
      the BECs in MS patients facilitate the massive influx of leukocytes into the
      brain parenchyma, which in turn induces irreversible demyelination, tissue damage
      and axonal dysfunction. Identification of ways to restore BBB function and
      promote its immune quiescence may therefore lead to the development of novel
      therapeutic regimes that not only specifically reduce leukocyte entry into the
      central nervous system but also restore the disturbed brain homeostasis. However,
      the complex network of molecular players that leads to BBB dysfunction in MS is
      yet to be fully elucidated. Recent discoveries unravelled a critical role for
      microRNAs (miRNAs) in controlling the function of the barrier endothelium in the
      brain. Here we will review the current knowledge on the involvement of BBB
      dysfunction in MS and the central role that miRNAs play in maintaining BBB
      integrity under inflammatory conditions. 

PMID- 25613506
TI  - MicroRNAs: newcomers into the ALS picture.
AB  - Amyotrophic lateral sclerosis (ALS) causes neurodegeneration of both upper and
      lower motor neurons and progressive muscle impairment, atrophy and death within
      approximately five years from diagnosis. The aetiology is still not clear but
      evidence obtained in animal models of the disease indicates a non-cell-autonomous
      mechanism with the active contribution of non-neuronal cells such as microglia,
      astrocytes, muscle and T cells, which differently participate to the diverse
      phases of the disease. Clinically indistinguishable forms of ALS occur as
      sporadic disease in the absence of known mutation, or can be initiated by genetic
      mutations. About two-third of familial cases are triggered by mutations of four
      genes that are chromosome 9 open reading frame 72 (C9ORF72), Cu/Zn superoxide
      dismutase (SOD1), fused in sarcoma/translocated in liposarcoma (FUS/TLS), TAR-DNA
      binding protein 43 (TDP43). There is at present no succesfull treatment against
      ALS and the identification of novel signalling pathways, molecular mechanisms and
      cellular mediators are still a major task in the search for effective therapies.
      MiRNAs are conserved, endogenous, non-coding RNAs that post-transcriptionally
      regulate protein expression. Produced as long primary transcripts, they are
      exported to the cytoplasm and further modified to obtain the mature miRNAs, with
      each step of their biogenesis being a potential step of regulation. There are
      more than 1000 different known human miRNA sequences, and more than 20-30% of all
      human protein-coding genes are likely controlled by miRNAs. This earns to miRNAs
      the definition of fine regulators of genetic networks. The discovery of the
      involvement of ALS mutated proteins TDP43 and FUS/TLS in miRNAs biogenesis
      strongly suggests a role of miRNA dysregulation also in ALS and many efforts are
      thus directed toward understanding the role of these small RNA molecules in the
      pathogenesis of ALS. The overall objective of this review is thus to highlight
      the emerging involvement of miRNAs in ALS. After a brief description of miRNA
      biogenesis and function, we discuss the effects of miRNA dysregulation in
      cellular and molecular pathways that lead to ALS neuroinflammation and
      neurodegeneration. In the last part, we focus on the mechanistic insights of
      miRNAs that might have implications for the development of novel neuroprotective
      agents against ALS, and on recent attempts to establish new molecular miRNA-based
      therapies. Paving the way for more comparative studies on neuroinflammatory and
      neurodegenerative mechanisms, this strategy indeed promises a broader impact on
      ALS. 

PMID- 25613508
TI  - MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review
      of the literature.
AB  - MicroRNAs are small RNAs involved in gene silencing. They play important roles in
      transcriptional regulation and are selectively and abundantly expressed in the
      central nervous system. A considerable amount of the human genome is comprised of
      tandem repeating nucleotide streams. Several diseases are caused by above
      threshold expansion of certain trinucleotide repeats occurring in a protein
      coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion
      disorders have a complex pathogenesis, various combinations of multiple
      coexisting pathways resulting in one common final consequence: selective
      neurodegeneration. Mutant protein and mutant transcript gain of toxic function
      are considered to be the core pathogenic mechanisms. The profile of microRNAs in
      CAG trinucleotide repeat disorders is scarcely described, however microRNA
      dysregulation has been identified in these diseases and microRNA-related
      intereference with gene expression is considered to be involved in their
      pathogenesis. Better understanding of microRNAs functions and means of
      manipulation promises to offer further insights into the pathogenic pathways of
      CAG repeat expansion disorders, to point out new potential targets for drug
      intervention and to provide some of the much needed etiopathogenic therapeutic
      agents. A number of disease-modifying microRNA silencing strategies are under
      development, but several implementation impediments still have to be resolved.
      CAG targeting seems feasible and efficient in animal models and is an appealing
      approach for clinical practice. Preliminary human trials are just beginning. 

PMID- 25613509
TI  - The emerging role of MicroRNA in schizophrenia.
AB  - MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that control gene
      expression post-transcriptionally by base pairing to mRNAs. MiRNAs are predicted
      to target ~50% of all protein-coding genes and functional studies indicate that
      they participate in the regulation of almost every cellular process. They also
      play a key role in pathogenetic mechanisms underlying several diseases, e.g.
      cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative
      diseases. Several miRNAs are expressed in the human brain where they contribute
      to equilibrium between maintenance and differentiation of neural stem cells.
      MiRNAs specific mechanisms of action and their roles in brain development and
      synaptic plasticity resulted in a great interest in the analysis of their
      potential role in the pathogenesis and pathophysiology of neuropsychiatric
      disorders. Currently, schizophrenia is one of the fields in psychiatry where
      miRNAs have been most widely investigated. The understanding of miRNAs role in
      schizophrenia has been achieved through association, functional and expression
      profiling studies on post mortem brain and peripheral tissues. Several studies
      identified association between neuropsychiatric disorders and variants in miRNAs
      including variations in miRNA/primary-/precursor-miRNAs sequences, in miRNAs
      biogenesis machinery genes, in the 3'UTR of target genes and in miRNAs
      expression. In summary, there is growing evidence that miRNAs exert a crucial
      role in gene expression regulation in the central nervous system and are altered
      in the development, presentation and response to treatment of psychiatric
      disorders. In this review we summarize the most significant results of
      experimental studies aimed at highlighting the involvement of human miRNAs in
      schizophrenia. 

PMID- 25613510
TI  - MicroRNAs: emerging role in the endogenous MU opioid system.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function as translational
      repressors and represent an important element in tissue development as well as
      disease. MiRNA sequences and their target sites in mRNAs show an extensive degree
      of conservation across species. A single miRNA is now believed to recognize the
      3'untranslated region of mRNAs in a sequence-specific manner to inhibit the
      protein expression of literally hundreds of targeted mRNAs. The human genome
      encodes more than 1000 miRNAs which target over 60% of mammalian and human
      transcripts. It is thus not surprising that expression changes in miRNAs can have
      a far-reaching impact on cellular functions, including the opioid system.
      Opioids, psychoactive chemicals that resemble morphine in their pharmacological
      effects are a class of potent analgesics used for treating various forms of acute
      and chronic pain. The mu opioid receptor is primarily responsible for opioid
      analgesia and anti-nociceptive tolerance. There is an ever-growing appreciation
      of miRNAs as important regulators of biological processes where opioids have an
      important impact, such as regulation of opioid receptors themselves. For example,
      a large number of splice variants of the primary transcript involve both 3' and
      5' splicing of the mu opioid receptor mRNA, many of which can potentially be
      targeted by miRNAs. Conversely, miRNAs can be regulated by opioids. Two mu opioid
      receptor agonists, morphine and fentanyl, display differential mechanisms of
      signalling linked to specific miRNA expression. Moreover, miRNA - opioid
      connections impact on neuronal cell development, drug addiction, pain perception,
      neuroimmune system interaction and cell proliferation and tumorigenesis. These
      aspects will be the subject of this review. 

PMID- 25613511
TI  - MicroRNAs in glioblastoma: role in pathogenesis and opportunities for targeted
      therapies.
AB  - Glioblastoma (GBM) is among the most lethal human cancers, being generally
      characterized by rapid diffuse and infiltrative growth and high level of cellular
      heterogeneity associated with therapeutic resistance. Despite remarkable advances
      in cancer theranostics, which resulted in significant improvement of clinical
      outcomes, patient survival remains under one year. In recent years, considerable
      progress has been made in understanding the role of small non-coding RNAs,
      designated microRNAs, in the pathogenesis of GBM. Indeed, microRNAs were found to
      play a critical role in multiple steps of the tumorigenic process, including
      cellular proliferation, apoptosis evasion, invasion, angiogenesis, and stemness.
      Moreover, the modulation of microRNA expression, using either antisense
      oligonucleotides or precursor/mimic sequences, revealed a tremendous potential
      for application in GBM-targeted therapeutic approaches, either per se or in
      combination with chemo- and/or radiotherapy. In this manuscript, we review the
      regulatory role of microRNAs in key cellular processes underlying GBM
      tumorigenesis, including migration and invasion, apoptosis evasion, angiogenesis
      and GBM stem-like cell proliferation/differentiation, and discuss the current
      knowledge on their potential as diagnostic, prognostic and predictive biomarkers
      in this disease. We also address the latest advances in microRNA-based
      therapeutic approaches for GBM, by summarizing the major achievements in in vitro
      and pre-clinical studies. The trends identified by these studies are highlighted
      in order to provide new prospects for future developments towards the successful
      treatment of GBM. 

PMID- 25613512
TI  - MicroRNA landscape in Alzheimer's disease.
AB  - Individual microRNAs and/or microRNA signatures were associated with Alzheimer's
      disease (AD). We report here the recent advances brought to the identification of
      microRNA changes in AD brain and their biological function in the molecular
      pathways associated with the disease. This field represents a fertile route to
      understand the pathogenic mechanisms underlying Alzheimer's disease. In addition
      we review recent studies aimed to discover promising biomarkers for AD diagnosis
      by microRNA expression profiles of biofluids from AD patients. 

PMID- 25613513
TI  - Quality of Life of Children with Cerebral Palsy: A Cross-Sectional  KIDSCREEN
      study in the Southern part of the Netherlands.
AB  - OBJECTIVE: To compare the quality of life (QoL) of 8-18 year old children with
      cerebral palsy (CP) in the Southern part of The Netherlands to a sample of
      European children from the general population and to investigate factors
      associated with possible differences. DESIGN: A cross-sectional KIDSCREEN-52 (by
      proxy version) study. SUBJECTS/PATIENTS: The parents of 80 out of 81 children
      (mean age 13.4 years, SD 2.98; 49 boys, 31 girls; Gross Motor Function
      Classification System (GMFCS) level 1: 21, 2: 5, 3: 16, 4: 18, 5: 20) agreed to
      participate. METHODS: Two-sample T-tests were used to compare domain scores
      between groups. Regression analysis was used to identify factors associated with
      deviant QoL scores. RESULTS: Parents reported significantly higher QoL for the
      domains of parent relation & home life and school environment. On the other hand
      significantly lower QoL was reported for the domains of psychical well-being,
      social support & peers, and social acceptance. Factors associated with deviant
      QoL scores were lower cognitive levels, less communication skills, and higher
      GMFCS levels. CONCLUSION: This study exposed several problem domains of QoL in
      children with CP living in the Southern part of the Netherlands. Several possible
      explanations for these findings are given. This information can be used to inform
      caregivers and service-providers.

PMID- 25613514
TI  - Age-related changes and effects of mild hypothermia on carotid artery reactivity
      in newborn rats.
AB  - Therapeutic hypothermia has become a standard neuroprotective treatment in term
      newborn infants following perinatal asphyxia. Hypothermia-induced changes in the
      reactivity of the vessels supplying the brain might play a role in its
      therapeutic or side effects. We investigated the putative age-related changes and
      the effect of clinically relevant cooling (33 degrees C) on the reactivity of the
      newborn rat carotid artery. Carotid artery rings from 2-3 days old and 9-10 days
      old rats were mounted in myographs and studied at 33 degrees C and 37 degrees C.
      Hypothermia did not significantly affect the contractions induced by KCl and
      U46619, nor the relaxations induced by acetylcholine (ACh), the nitric oxide (NO)
      donor sodium nitroprusside (SNP), the NO-independent stimulator of soluble
      guanylate cyclase (sGC) BAY 41-2272, the beta -adrenoceptor agonist
      isoproterenol, the adenylate cyclase activator forskolin, and acute hypoxia (PO2
      3 kPa). The relaxations induced by ACh, isoproterenol, the beta 2-adrenoceptor
      agonist salbutamol, the beta 3-adrenoceptor agonist CL-316243 and acute hypoxia
      increased with postnatal age and were impaired by endothelium removal or by
      inhibition of NO synthase (L-NAME) or sGC (ODQ). In contrast, the relaxations
      induced by SNP, BAY 41-2272 and forskolin were endothelium-independent and did
      not change with age. In conclusion, mild hypothermia (33 degrees C) does not
      affect the reactivity of neonatal rat carotid arteries. Our data suggest a
      reduced NO bioavailability in the carotid artery during the first days of life.
      This transient reduction in endothelium-dependent relaxation might play a role in
      the adaptation of the circulatory system to birth and in the neonatal vascular
      response to insults such as hypoxia.

PMID- 25613515
TI  - Predictors of Ominous Outcome in Infants Undergone to Cardiac Surgery and
      Cardiopulmonary by-Pass: S100B Protein.
AB  - S100B protein has been recently proposed as a consolidated marker of brain damage
      and death in adult, children and newborn patients. The present study evaluates
      whether the longitudinal measurement of S100B at different perioperative time
      points may be a useful tool to identify the occurrence of perioperative early
      death in congenital heart disease (CHD) newborns. We conducted a case-control
      study in 88 CHD infants, without pre-existing neurological disorders or other co
      morbidities, of whom 22 were complicated by perioperative death in the first week
      from surgery. Control group was composed by 66 uncomplicated CHD infants matched
      for age at surgical procedure. Blood samples were drawn at five predetermined
      time-points before during and after surgery. In all CHD children, S100B values
      showed a pattern characterized by a significant increase in protein's
      concentration from hospital admission up to 24-h after procedure reaching their
      maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the
      surgical procedure. Moreover, S100B concentrations in CHD death group were
      significantly higher (P<0.01) than controls at all monitoring time-points. The
      ROC curve analysis showed that S100B measured before surgical procedure was the
      best predictor of perioperative death, among a series of clinical and laboratory
      parameters, reaching at a cut-off of 0.1 MUg/L a sensitivity of 100% and a
      specificity of 63.7%. The present data suggest that in CHD infants biochemical
      monitoring in the perioperative period is becoming possible and S100B can be
      include among a series of parameters for adverse outcome prediction.

PMID- 25613516
TI  - Olfactory ensheathing cells protect cortical neuron cultures exposed to hypoxia.
AB  - A peculiar population of glial cells, Olfactory Ensheathing Cells (OECs), are
      able to support the continuous neuronal turn-over and sheathe olfactory axons. In
      vitro, they stimulate axonal growth, as produce several neurotrophic factors
      (GFs); in vivo they promote remyelination of damaged axons. In this in vitro
      study, OEC effects on survival of cortical neurons exposed to hypoxia were
      examined. Rat co-cultures of OECs and cortical neurons were placed both in normal
      and hypoxic conditions; subsequently cells were analyzed by immunocytochemistry.
      Furthermore, some neuronal cultures were grown with Glial cell Derived
      Neurotrophic Factor (GDNF) or basic Fibroblast Growth Factor (bFGF) to
      tentatively rescue cells from oxygen deprivation. Some cortical neurons grown in
      both conditions were considered as control cells. Some neuronal cultures were
      feed with conditioned medium from OECs. We show that both in co-cultures and with
      GFs-treatment there was an increase of the number of neurons in comparison with
      control cultures. Moreover, these neurons formed a rich axonal outgrowth. OEC
      conditioned media did not affect the cell survival. In hypoxic cultures the
      neuron number was very low both in controls and in GFs-treated neurons, while in
      co-cultures and in OEC-conditioned media cultures an increased neuronal survival
      was observed. These data suggest that OECs promote the survival of neurons in
      vitro exposed to hypoxia exerting a protective influence. Since some experiments
      in vivo have shown that injury is often characterized by secondary insults,
      ischemia or hypoxia, our results suggest that OECs might be considered a possible
      approach for restoration in injuries.

PMID- 25613517
TI  - Chlorinated, brominated and fluorinated organic pollutants in African Penguin
      eggs: 30 years since the previous assessment.
AB  - The African Penguin population has drastically declined over the last 100 years.
      Changes in food availability due to over-fishing and other oceanographic changes
      seem to be major causes. However, it has also been 30 years since organic
      pollutants as a potential factor have been assessed. We analysed penguin eggs
      collected in 2011 and 2012 from two breeding colonies 640 km apart: Robben Island
      near Cape Town on the Atlantic Ocean coast, and Bird Island near Port Elizabeth
      on the Indian Ocean coast of South Africa. We quantified organochlorine
      pesticides, brominated flame retardants, and perfluorinated compounds (PFCs).
      Compared to 30 years ago, concentrations of SigmaDDT have remained about the same
      or slightly lower, while SigmaPCBs declined almost four-fold. The use of DDT in
      malaria control is unlikely to have contributed. PFCs were detected in all eggs.
      Indications (non-significant) of eggshell thinning associated with SigmaDDT and
      SigmaPCB was found. It seems therefore that the concentrations of measured
      organic pollutants the African Penguin eggs are not contributing directly to its
      current demise, but concerns remain about thinner shells and desiccation. Effects
      of combinations of compounds and newer compounds cannot be excluded, as well as
      more subtle effects on reproduction, development, and behaviour.

PMID- 25613518
TI  - Calycosin and genistein induce apoptosis by inactivation of HOTAIR/p-Akt
      signaling pathway in human breast cancer MCF-7 cells.
AB  - BACKGROUND: Calycosin and genistein are the two main components of isoflavones.
      Previously, we reported that these compounds display antitumor activities in the
      breast cancer cell lines MCF-7 and T47D. In the present study, we investigated
      the mechanism of action of calycosin and genistein, and their respective
      efficacies as potential therapies for the treatment of breast carcinoma in the
      clinic. METHODS: MCF-7 cells were treated with calycosin or genistein. Cell
      proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The
      expression level of phosphorylated Akt protein was determined by western
      blotting. Expression level of HOTAIR was quantified by real-time PCR. RESULTS:
      Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF
      7 breast cancer cells, especially after treatment with calycosin. Treatment of
      MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of
      Akt, and decreased expression of its downstream target, HOTAIR. CONCLUSION:
      Calycosin is more effective in inhibiting breast cancer growth in comparison with
      genistein, through its regulation of Akt signaling pathways and HOTAIR
      expression.

PMID- 25613520
TI  - Quantitative analysis of the morphological changes of the pubic symphyseal face
      and the auricular surface and implications for age at death estimation.
AB  - Age estimation methods are often based on the age-related morphological changes
      of the auricular surface and the pubic bone. In this study, a mathematical
      approach to quantify these changes has been tested analyzing the curvature
      variation on 3D models from CT and laser scans. The sample consisted of the 24
      Suchey-Brooks (SB) pubic bone casts, 19 auricular surfaces from the Buckberry and
      Chamberlain (BC) "recording kit" and 98 pelvic bones from the Terry Collection
      (Smithsonian Institution). Strong and moderate correlations between phases and
      curvature were found in SB casts (rho 0.60-0.93) and BC "recording kit" (rho 0.47
      0.75), moderate and weak correlations in the Terry Collection bones (pubic bones:
      rho 0.29-0.51, auricular surfaces: rho 0.33-0.50) but associated with large
      individual variability and overlap of curvature values between adjacent decades.
      The new procedure, requiring no expert judgment from the operator, achieved
      similar correlations that can be found in the classic methods. 

PMID- 25613521
TI  - The bone morphogenetic protein system and the regulation of ovarian follicle
      development in mammals.
AB  - The bone morphogenetic protein (BMP) family consists of several growth factor
      proteins that belong to the transforming growth factor-beta (TGF-beta)
      superfamily. BMPs bind to type I and type II serine-threonine kinase receptors,
      and transduce signals through the Smad signalling pathway. BMPs have been
      identified in mammalian ovaries, and functional studies have shown that they are
      involved in the regulation of oogenesis and folliculogenesis. This review
      summarizes the role of the BMP system during formation, growth and maturation of
      ovarian follicles in mammals. 

PMID- 25613522
TI  - Improving the neutral phytase activity from Bacillus amyloliquefaciens DSM 1061
      by site-directed mutagenesis.
AB  - Neutral phytase is used as a feed additive for degradation of anti-nutritional
      phytate in aquatic feed industry. Site-directed mutagenesis of Bacillus
      amyloliquefaciens DSM 1061 phytase was performed with an aim to increase its
      activity. Mutation residues were chosen based on multiple sequence alignments and
      structure analysis of neutral phytsaes from different microorganisms. The
      mutation sites on surface (D148E, S197E and N156E) and around the active site
      (D52E) of phytase were selected. Analysis of the phytase variants showed that the
      specific activities of mutants D148E and S197E remarkably increased by about 35
      and 13% over a temperature range of 40-75  degrees C at pH 7.0, respectively. The
      k cat of mutants D148E and S197E were 1.50 and 1.25 times than that of the wild
      type phytase, respectively. Both D148E and S197E showed much higher
      thermostability than that of the wild-type phytase. However, mutants N156E and
      D52E led to significant loss of specific activity of the enzyme. Structural
      analysis revealed that these mutations may affect conformation of the active site
      of phytase. The present mutant phytases D148E and S197E with increased activities
      and thermostabilities have application potential as additives in aquaculture
      feed.

PMID- 25613523
TI  - Muscle activation pattern and onset times during a semi-orthostatic, unilateral
      closed-kinetic hip extension exercise in adolescent males.
AB  - The hip extensors are an important muscle group for sporting and functional
      movements, but assessing this muscle group for musculoskeletal dysfunction and
      strength testing has been performed in adult males and females as a prone, open
      chain exercise, which provides little posture specificity for locomotive
      activities. Given the importance of closed-kinetic chain exercises for strength
      and rehabilitation requirements, there is an obvious need to assess hip extension
      but little is known about executing a closed-kinetic chain hip extension exercise
      for adolescents. Therefore, the aim of this study was to ascertain hip extensor
      muscle activation pattern and force production using a semi-orthostatic position
      while performing a unilateral closed-kinetic hip extension exercise. Fourteen
      young healthy adolescent male participants performed three maximal repetitions of
      closed-kinetic chain left and right hip extension on a glute machine.
      Electromyography (EMG) from left and right rectus femoris (RF), gluteus maximus
      (GM), and biceps femoris (BF) was recorded and RF, GM, and BF EMG mean amplitude,
      EMG area and onset times were analysed. There was no significant difference in
      EMG mean amplitude and EMG area between RF, GM, and BF but the right hip showed a
      significantly higher EMG (p < 0.05) than the left hip. The relative onset
      difference between GM and BF was similar in both hips, suggesting that there was
      no dominant muscle firing order. The closed-kinetic chain hip extension could be
      advantageous when assessing neuromuscular function and training muscle strength
      because the semi-orthostatic position of hip extension exercise provides a
      posture similar to functional activities. 

PMID- 25613524
TI  - Effects of a community-based multimodal exercise program on physical function and
      quality of life in cancer survivors: a pilot study.
AB  - The purpose of this single-arm pilot study was to examine the effects of a
      community-based multimodal exercise program on: physical function (Timed-Up-and
      Go [TUG], 6-min walk test [6MWT], leg and chest press strength, and functional
      reach [FR]); and quality of life, QoL [FACT-G]), in cancer survivors. Fifty-nine
      cancer survivors (91.5% female; mean age 59 +/- 12 years) completed supervised
      exercise training for 90 min twice weekly for 12 weeks. Exercise training
      consisted of 30 min of each of the following: (1) aerobic conditioning; (2)
      resistance training; and (3) balance and flexibility training. Pre-post-outcome
      measures were compared for statistically significant differences (p < 0.01) and
      were related to the International Classification of Functioning, Disability and
      Health Model. Effect sizes (ES), minimal clinically important differences, and
      minimal detectable change at 90% confidence intervals were calculated.
      Participants decreased TUG time by 21.1% and walked 15.5% farther during 6-MWT (p
      < 0.001). Leg and chest press strength increased by 34.5% and 32.7%, respectively
      (p < 0.001). FR increased by 15.1% (p < 0.001). Significant improvements for
      physical well-being (13.9%), emotional well-being (6.7%), functional well-being
      (13.0%), and total well-being (9.6%) were found (p < 0.01). Improvements in
      physical function and QoL showed "moderate to large" ESs indicating improvements
      in physical function and QoL are clinically meaningful. 

PMID- 25613525
TI  - Predicting oculomotor behaviour from correlated populations of posterior parietal
      neurons.
AB  - Oculomotor function critically depends on how signals representing saccade
      direction and eye position are combined across neurons in the lateral
      intraparietal (LIP) area of the posterior parietal cortex. Here we show that
      populations of parietal neurons exhibit correlated variability, and that using
      these interneuronal correlations yields oculomotor predictions that are more
      accurate and also less uncertain. The structure of LIP population responses is
      therefore essential for reliable read-out of oculomotor behaviour. 

PMID- 25613526
TI  - Inkjet printing of upconversion nanoparticles for anti-counterfeit applications.
AB  - Patterning of upconversion luminescent materials has been widely used for anti
      counterfeit and security applications, where the preferred method should be easy,
      fast, multicolor, high-throughput and designable. However, conventional
      patterning methods are complex and inflexible. Here, we report a digital and
      flexible inkjet printing based approach for producing high-resolution and high
      luminescence anti-counterfeit patterns. We successfully printed different
      multicolor luminescent patterns by inkjet printing of upconversion nanoparticles
      with controlled and uniform luminescence intensity through optimizing the inks
      and substrates. Combined with another downconversion luminescent material, we
      achieved two different patterns in the same area, which show up separately under
      excitation by different wavelength laser sources. The developed technology is
      promising to use one single substrate for carrying abundant information by
      printing multilayer patterns composed of luminescent materials with different
      excitation light sources. 

PMID- 25613527
TI  - Frontal white matter hyperintensity predicts lower urinary tract dysfunction in
      older adults with amnestic mild cognitive impairment and Alzheimer's disease.
AB  - AIM: Lower urinary tract symptoms often limit activities of daily life and impair
      quality of life in the elderly. The purpose of the present study was to determine
      whether regional white matter hyperintensity (WMH) can predict lower urinary
      tract symptoms in elderly with amnestic mild cognitive impairment or Alzheimer's
      disease. METHODS: The participants were 461 patients aged 65-85 years diagnosed
      with amnestic mild cognitive impairment or Alzheimer's disease. Patients and
      their caregivers were asked about symptoms of lower urinary tract symptoms
      (urinary difficulty, frequency and incontinence). Cognition, behavior and
      psychological symptoms of dementia and medication were evaluated. WMH and brain
      atrophy were analyzed using an automatic segmentation program. Regional WMH was
      evaluated in the frontal, parietal, temporal and occipital lobes. RESULTS:
      Patients with urinary incontinence showed significantly greater volume of WMH.
      WMH increased with age, especially in the frontal lobe. WMH in the frontal lobe
      was closely associated with urinary incontinence after adjustment for brain
      atrophy and classical confounding factors. CONCLUSIONS: Frontal WMH was a
      predictive factor for urinary incontinence in older adults with amnestic mild
      cognitive impairment or Alzheimer's disease. Urinary incontinence in demented
      older adults is not an incidental event, and careful insight into regional WMH on
      brain magnetic resonance imaging might greatly help in diagnosing individuals
      with a higher risk of urinary incontinence.

PMID- 25613528
TI  - Primary closure and rate of bile leak following laparoscopic common bile duct
      exploration via choledochotomy.
AB  - BACKGROUND: Choledocholithiasis is traditionally managed by endoscopic retrograde
      cholangiopancreatography or T-tube insertion following common bile duct
      exploration. This study examined the efficacy and safety of primary duct closure
      following laparoscopic common bile duct exploration (LCBDE) via choledochotomy.
      METHODS: Between September 2011 and September 2013, 157 consecutive patients
      underwent LCBDE via choledochotomy. RESULTS: Of 157 LCBDE procedures, 138 (87.9%)
      were successfully completed with primary closure of the choledochotomy. Eight
      patients (5.1%) underwent closure with T-tube drainage after choledochotomy and
      11 patients (7.0%) were converted to open surgery. The biliary tree was free of
      stones at the end of surgery in 154 patients (98.1%). Postoperative bile leak
      occurred in 6 patients (3.8%). The median follow-up period was 18 (2-33) months,
      with no evidence of further bile duct stones or bile duct stricture in any
      patients. Univariable analysis revealed that successful duct clearance (p =
      0.010) and diameter of the common bile duct (p < 0.001) were two significant risk
      factors for bile leak. CONCLUSIONS: Primary duct closure following LCBDE is
      effective and safe for the management of choledocholithiasis. The postoperative
      bile leak rate may be low in skilled laparoscopic surgeons with a careful
      selection of patients.

PMID- 25613529
TI  - Comparative behavioral and neurochemical analysis of phenytoin and valproate
      treatment on epilepsy induced learning and memory deficit: Search for add on
      therapy.
AB  - Our previous work demonstrated, chronic epilepsy affects learning and memory of
      rodents along with peculiar neurochemical changes in discrete brain parts. Most
      commonly used antiepileptic drugs (phenytoin and sodium valproate) also worsen
      learning and memory in the patients with epilepsy. Therefore this study was
      designed to carry out comparison of behavioral and neurochemical changes with
      phenytoin and sodium valproate treatment in pentylenetetrazole-kindling induced
      learning and memory deficit to devise add on therapy for this menace. For the
      experimental epilepsy, animals were kindled using PTZ (35 mg/kg; i.p., at 48 +/-
      2 h intervals) and successful kindled animals were involved in the study. These
      kindled animals were treated with saline, phenytoin (30 mg/kg/day, i.p.) and
      sodium valproate (300 mg/kg/day, i.p.) for 20 days. These animals were challenged
      with PTZ challenging dose (35 mg/kg) on day 5, 10, 15 and 20 to evaluate the
      effect on seizure severity score on different days. Effect on learning and memory
      was evaluated using elevated plus maze and passive shock avoidance paradigm. On
      day 20, after behavioral evaluations, animals were sacrificed to analyze
      glutamate, GABA, norepinephrine, dopamine, serotonin, total nitrite level and
      acetylcholinesterase level in cortex and hippocampus. Behavioral evaluations
      suggested that phenytoin and sodium valproate treatment significantly reduced
      seizure severity in the kindled animals, while sodium valproate treatment
      controls seizures with least memory deficit in comparison to phenytoin.
      Neurochemical findings revealed that elevated cortical acetylcholinesterase level
      could be one of the responsible factors leading to memory deficit in phenytoin
      treated animals. However sodium valproate treatment reduced cortical
      acetylcholinesterase level and had least debilitating consequences on memory
      deficit. Therefore, attenuation of elevated AChE activity can be one of add-on
      approach for management of memory deficit associated with conventional AEDs. 

PMID- 25613530
TI  - Expression and clinical significance of the HIF-1a/ET-2 signaling pathway during
      the development and treatment of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a major health problem in reproductive-aged
      women worldwide, but the precise pathogenesis of PCOS remains unclear. Our
      previous study revealed that hypoxia-inducible factor (HIF)-1a mediated
      endothelin (ET)-2 signaling plays an important role in ovulation in rats.
      Therefore, the present study used a PCOS rat model to test the hypotheses that
      HIF-1a signaling is expressed and inhibited in ovaries during PCOS formation and
      that the HIF-1a/ET-2 signaling pathway is a target of dimethyldiguanide (DMBG) in
      the clinical treatment of PCOS. First, the development of a PCOS model and the
      effect of DMBG treatment were examined through ovarian histology and serum
      hormone levels, which were consistent with previous reports. Second, HIF-1a and
      ET-2 expression were detected by immunohistochemistry and western blot. The
      results showed decreased HIF-1a/ET-2 expression in the ovaries of PCOS rats,
      whereas DMBG treatment reversed the protein decreases and improved the PCOS
      symptoms. Third, to understand the molecular mechanism, HIF-1a/ET-2 mRNA
      expression was also examined. Interestingly, HIF-1a mRNA increased in the ovaries
      of PCOS rats, while ET-2 mRNA decreased, indicating that HIF-1a protein
      degradation may be involved in POCS development and treatment. Finally, HIF
      prolyl hydroxylase (PHD) activity was examined to further clarify the
      contribution of HIF-1a signaling to the development and treatment of PCOS. The
      results suggested that the inhibition of HIF-1a/ET-2 signaling may be caused by
      increased PHD activity in PCOS. DMBG-treated PCOS may further activate HIF-1a
      signaling at least partly through inhibiting PHD activity. Taken together, these
      results indicate that HIF-1a signaling is inhibited in a PCOS rat model through
      increasing PHD activity. DMBG treatment improved PCOS by rescuing this pathway,
      suggesting that HIF-1a signaling plays an important role in the development and
      treatment of PCOS. This HIF-1a-mediated ET-2 signaling pathway may be an
      important mechanism regulating PCOS formation and treatment in mammalian ovaries
      in vivo and should be a new clinical target for PCOS prevention and treatment in
      the future. 

PMID- 25613531
TI  - Paraphyly of the subgenus Anaphlebotomus and creation of Madaphlebotomus subg.
      nov. (Phlebotominae: Phlebotomus).
AB  - The systematic position of the Malagasy Phlebotomus (Diptera: Psychodidae)
      species was assessed in molecular phylogenetic studies. Three molecular markers
      were sequenced: cytochrome b of the mitochondrial DNA; ITS2, and the D8 domain of
      the ribosomal DNA. The following species were studied: Phlebotomus
      (Anaphlebotomus) berentiensis, Phlebotomus (Anaphlebotomus) fertei, Phlebotomus
      (Anaphlebotomus) fontenillei, Phlebotomus (Anaphlebotomus) vaomalalae and
      Phlebotomus (Anaphlebotomus) vincenti from Madagascar; Phlebotomus
      (Anaphlebotomus) stantoni from Asia, and Phlebotomus (Anaphlebotomus) rodhaini
      from Africa. The following outgroups were selected: Phlebotomus (Euphlebotomus)
      argentipes, Phlebotomus (Euphlebotomus) barguesae, Phlebotomus (Larroussius)
      perfiliewi s.l. and Phlebotomus (Adlerius) simici. Each marker analysed by
      maximum parsimony and maximum likelihood supports the monophyly of the Malagasy
      Phlebotomus spp. Consequently, we create a new subgenus for these species:
      Madaphlebotomus subg. nov. This molecular individualization is reinforced by the
      originality of their spermathecae and by the fact that their geographical
      distribution is limited to Madagascar, and considers the high level of endemism
      on this island. 

PMID- 25613532
TI  - Clinically significant novel biomarkers for prediction of first ever myocardial
      infarction: the Tromso Study.
AB  - BACKGROUND: Identification of individuals with high risk for first-ever
      myocardial infarction (MI) can be improved. The objectives of the study were to
      survey multiple protein biomarkers for association with the 10-year risk of
      incident MI and identify a clinically significant risk model that adds
      information to current common risk models. METHODS AND RESULTS: We used an
      immunoassay platform that uses a sensitive, sample-efficient molecular counting
      technology to measure 51 proteins in samples from the fourth survey (1994) in the
      Tromso Study, a longitudinal study of men and women in Tromso, Norway. A case
      control design was used with 419 first-ever MI cases (169 females/250 males) and
      398 controls (244 females/154 males). Of the proteins measured, 17 were
      predictors of MI when considered individually after adjustment for traditional
      risk factors either in men, women, or both. The 6 biomarkers adjusted for
      traditional risk factors that were selected in a multivariable model (odds ratios
      [OR] per standard deviation) using a stepwise procedure were apolipoprotein
      B/apolipoprotein A1 ratio (1.40), kallikrein (0.73), lipoprotein a (1.29), matrix
      metalloproteinase 9 (1.30), the interaction term IP-10/CXCL10*women (0.69), and
      the interaction term thrombospondin 4*men (1.38). The composite risk of these
      biomarkers added significantly to the traditional risk factor model with a net
      reclassification improvement of 14% (P=0.0002), whereas the receiver operating
      characteristic area increased from 0.757 to 0.791, P=0.0004. CONCLUSIONS: Novel
      protein biomarker models improve identification of 10-year MI risk above and
      beyond traditional risk factors with 14% better allocation to either high or low
      risk group.

PMID- 25613533
TI  - Differentiated thyroid cancer patients more than 60 years old paradoxically show
      an increased life expectancy.
AB  - The aim of this study was to compare the overall survival of a large, single
      center cohort of patients who had differentiated thyroid cancer (DTC) with that
      of a matched general population. METHODS: We analyzed 2,428 consecutive patients
      who had DTC and underwent treatment from 1965 to 2013 at the Department of
      Nuclear Medicine, University Hospital of Munster, Munster, Germany, according to
      international standards. Patients were classified on the basis of the current,
      seventh edition of the American Joint Committee on Cancer/Union for International
      Cancer Control classification system. Additionally, a subgroup analysis with
      regard to age at diagnosis was performed. The overall survival of the patients
      was compared with the expected survival of the general population on the basis of
      age and sex, as provided by the Federal Statistical Office of Germany. RESULTS:
      Compared with the expected survival, the overall survival of patients with stage
      I disease paradoxically was significantly better (P < 0.001). In the subgroup
      analysis, a significantly lower mortality rate was observed in elderly patients
      (>=60 y old) with stage I disease. On the other hand, patients between 20 and 45
      y of age and with distant metastases at diagnosis had a significantly increased
      standardized mortality rate. In contrast, other patients with stage II disease
      and more than 45 y old had a normal mortality rate. The mortality rate was
      significantly increased in all patients with stage IVC disease. CONCLUSION: Older
      patients with more limited disease paradoxically had better survival than would
      be expected on the basis of age and sex, whereas young adults as well as patients
      more than 45 y old and with distant metastases had increased mortality rates. For
      all other DTC patients, regardless of age or TNM stage, no significant survival
      difference was seen.

PMID- 25613534
TI  - Risk stratification of metastatic neck nodes by CT and PET in patients with head
      and neck cancer receiving definitive radiotherapy.
AB  - The aim of this study was to investigate the prognostic impact of CT and (18)F
      FDG PET/CT on the outcome of metastatic neck node (MNN) in patients with head and
      neck cancer receiving definitive radiotherapy or chemoradiotherapy. METHODS: This
      patient-based study included 91 patients diagnosed with pharyngeal cancers with
      MNN (N1, 15; N2, 70; N3, 6). All had pretreatment CT and PET/CT before definitive
      chemoradiotherapy/radiotherapy. Parameters of MNNs for each patient, including
      maximal diameter, nodal volume, radiologic central necrosis, maximum standardized
      uptake value, metabolic tumor volume, and total lesion glycolysis (TLG), were
      retrieved for the analysis. Nodal relapse-free survival (NRFS) and survivals were
      calculated using the Kaplan-Meier method. Independent predictors were identified
      using Cox regression analysis. RESULTS: After a median follow-up of 18 mo, 64
      patients remained nodal relapse-free, and 27 experienced neck recurrence.
      Multivariate analysis showed that the application of 40% of the maximal uptake of
      nodal TLG (N-TLG40%) 38 g or greater (P = 0.03; hazard ratio, 2.63; 95%
      confidence interval, 1.10-6.30) and radiologic necrosis on CT scan (P = 0.001;
      hazard ratio, 10.99; 95% confidence interval, 2.56-47.62) were 2 adverse features
      for NRFS. Patients who had an N-TLG40% 38 g or greater and central radiologic
      necrosis had a significantly inferior 2-y NRFS (53% vs. 77% and 45% vs. 95%,
      respectively). CONCLUSION: The outcome of MNNs in patients with head and neck
      cancer receiving chemoradiotherapy/radiotherapy can be predicted according to
      radiologic necrosis and N-TLG40% value. The 2 adverse features should be
      validated in future trials. In this way, patients can be treated alternatively or
      aggressively.

PMID- 25613535
TI  - 18F-FDG PET/CT and lung cancer: value of fourth and subsequent posttherapy follow
      up scans for patient management.
AB  - The Centers for Medicare and Medicaid Services recently ruled that only 3
      posttherapy follow-up (18)F-FDG PET/CT scans are funded for a tumor type per
      patient and any additional follow-up PET/CT scans will be funded at the
      discretion of the local Medicare administrator. The purpose of this study was to
      evaluate the added value of 4 or more follow-up PET/CT scans to clinical
      assessment and impact on patient management. METHODS: This was an institutional
      review board-approved, retrospective study. A total of 1,171 patients with biopsy
      proven lung cancer who had undergone (18)F-FDG PET/CT at a single tertiary center
      from 2001 to 2013 were identified. Among these, 85 patients (7.3%) had undergone
      4 or more follow-up PET/CT scans, for a total of 285 fourth and subsequent follow
      up PET/CT scans. Median follow-up from the fourth follow-up PET/CT scan was 31.4
      mo (range, 0-155.2 mo). The follow-up PET/CT scan results were correlated with
      clinical assessment and treatment changes. RESULTS: Of the 285 fourth and
      subsequent follow-up PET/CT scans, 149 (52.28%) were interpreted as positive and
      136 (47.7%) as negative for recurrence or metastasis. A total of 47 patients
      (55.3%) died during the study period. PET/CT identified recurrence or metastasis
      in 44.3% of scans performed without prior clinical suspicion and ruled out
      recurrence or metastasis in 24.2% of scans performed with prior clinical
      suspicion. The PET/CT scan resulted in a treatment change in 28.1% (80/285) of
      the patients. New treatment was initiated for 20.4% (58/285) of the scans,
      treatment was changed in 5.6% (16/285), and ongoing treatment was stopped in 2.1%
      (6/285). CONCLUSION: The fourth and subsequent (18)F-FDG PET/CT scans performed
      during follow-up after completion of primary treatment added value to clinical
      assessment and changed management 28.1% of the time.

PMID- 25613536
TI  - PET imaging of translocator protein (18 kDa) in a mouse model of Alzheimer's
      disease using N-(2,5-dimethoxybenzyl)-2-18F-fluoro-N-(2-phenoxyphenyl)acetamide.
AB  - Herein we aimed to evaluate the utility of N-(2,5-dimethoxybenzyl)-2-(18)F-fluoro
      N-(2-phenoxyphenyl)acetamide ((18)F-PBR06) for detecting alterations in
      translocator protein (TSPO) (18 kDa), a biomarker of microglial activation, in a
      mouse model of Alzheimer's disease (AD). METHODS: Wild-type (wt) and AD mice
      (i.e., APP(L/S)) underwent (18)F-PBR06 PET imaging at predetermined time points
      between the ages of 5-6 and 15-16 mo. MR images were fused with PET/CT data to
      quantify (18)F-PBR06 uptake in the hippocampus and cortex. Ex vivo
      autoradiography and TSPO/CD68 immunostaining were also performed using brain
      tissue from these mice. RESULTS: PET images showed significantly higher
      accumulation of (18)F-PBR06 in the cortex and hippocampus of 15- to 16-mo-old
      APP(L/S) mice than age-matched wts (cortex/muscle: 2.43 +/- 0.19 vs. 1.55 +/-
      0.15, P < 0.005; hippocampus/muscle: 2.41 +/- 0.13 vs. 1.55 +/- 0.12, P < 0.005).
      And although no significant difference was found between wt and APP(L/S) mice
      aged 9-10 mo or less using PET (P = 0.64), we were able to visualize and quantify
      a significant difference in (18)F-PBR06 uptake in these mice using
      autoradiography (cortex/striatum: 1.13 +/- 0.04 vs. 0.96 +/- 0.01, P < 0.05;
      hippocampus/striatum: 1.266 +/- 0.003 vs. 1.096 +/- 0.017, P < 0.001). PET
      results for 15- to 16-mo-old mice correlated well with autoradiography and
      immunostaining (i.e., increased (18)F-PBR06 uptake in brain regions containing
      elevated CD68 and TSPO staining in APP(L/S) mice, compared with wts). CONCLUSION:
      (18)F-PBR06 shows great potential as a tool for visualizing TSPO/microglia in the
      progression and treatment of AD.

PMID- 25613537
TI  - PMPA for nephroprotection in PSMA-targeted radionuclide therapy of prostate
      cancer.
AB  - Radioactive ligands for the prostate-specific membrane antigen (PSMA) are under
      development for therapy of metastasized prostate cancer. Since PSMA expression is
      also found in the kidneys, renal tracer uptake can be dose-limiting. Because
      kidney kinetics differ from tumor kinetics, serial application of PSMA inhibitors
      such as 2-(phosphonomethyl)pentanedioic acid (PMPA) may improve the kidney-to
      tumor ratio. In this study, we evaluated the effect of PMPA on the
      biodistribution of 2 promising PSMA ligands. METHODS: Human prostate cancer
      xenografts (LNCaP) were transplanted subcutaneously into mice. After injection of
      (125)I-MIP1095, a 16-h latency period was allowed for tracer clearance from the
      blood and renal calices. After baseline scintigraphy, PMPA was injected in doses
      of 0.2-50 mg/kg (n = 3 per dose, 5 controls), followed by scans at 2, 4, 6, and
      24 h after PMPA injection. Kidney and tumor displacement was determined as a
      percentage of baseline. A shortened but similar design was used to evaluate the
      PSMA ligand MIP1404, which contains a chelate for (99m)Tc/rhenium. RESULTS: PMPA
      injection 16 h after MIP1095 translated into a rapid and quantitative relevant
      displacement of renal activity. Tumor uptake was reduced to a significantly
      lesser extent in a dose-dependent manner. PMPA doses of 0.2-1 mg/kg appear
      optimal for sustaining nearly complete tumor uptake while simultaneously
      achieving near-total blocking of specific renal PSMA binding. The effect was
      successfully validated with the PSMA ligand MIP1404. CONCLUSION: PSMA-targeted
      radionuclide therapy can benefit from serial PMPA comedication by reducing off
      target radiation to the kidneys. These data will be used for a first
      approximation in clinical translation, although in patients an optimization of
      the dose and time schedule may be necessary.

PMID- 25613538
TI  - PET/CT-derived whole-body and bone marrow dosimetry of 89Zr-cetuximab.
AB  - PET/CT imaging allows for image-based estimates of organ and red marrow (RM)
      residence times. The aim of this study was to derive PET/CT-based radiation
      dosimetry for (89)Zr-cetuximab, with special emphasis on determining RM-absorbed
      dose. METHODS: Seven patients with colorectal cancer received 36.9 +/- 0.8 MBq of
      (89)Zr-cetuximab within 2 h after administration of a therapeutic dose of 500
      mg.m(-2) of cetuximab. Whole-body PET/CT scans and blood samples were obtained at
      1, 24, 48, 94, and 144 h after injection. RM activity concentrations were
      calculated from manual delineation of the lumbar vertebrae and blood samples,
      assuming a fixed RM-to-plasma activity concentration ratio (RMPR) of 0.19. The
      cumulated activity was calculated as the area under the curve of the organ time
      activity data (liver, lungs, kidneys, spleen, and RM), assuming physical decay
      after the last scan. The residence time for each organ was derived by dividing
      the cumulated activity with the total injected activity. The residence time in
      the remainder of the body was calculated as the maximum possible residence time
      minus the sum of residence time of source organs, assuming no excretion during
      the time course of the scans. The (self and total) RM- and organ-absorbed doses
      and effective whole-body radiation dose were obtained using dose conversion
      factors from OLINDA/EXM 1.1. Several simplified 3-time-point dosimetry approaches
      were also evaluated. RESULTS: The first approach yielded self and total RM doses
      of 0.17 +/- 0.04 and 0.51 +/- 0.06 mGy.MBq(-1), respectively. The second approach
      deviated by -21% in self-dose and -6% in total dose. RMPR increased over time in
      5 of 7 patients. The highest (89)Zr-absorbed dose was observed in the liver with
      2.60 +/- 0.78 mGy.MBq(-1), followed by the kidneys, spleen, and lungs, whereas
      the effective whole-body dose was 0.61 +/- 0.09 mSv.MBq(-1). The simplified 3
      time-point (1, 48, and 144 h) dosimetry approach deviated by at most 4% in both
      organ-absorbed doses and effective dose. CONCLUSION: Although the total RM dose
      estimates obtained with the 2 approaches differed only by at most 6%, the image
      based approach is preferred because it accounts for nonconstant RMPR. The number
      of successive scans can be reduced to 3 without affecting effective dose
      estimates.

PMID- 25613539
TI  - Effects of advanced age and renal dysfunction on the single- and repeated-dose
      pharmacokinetics of modified-release flupirtine.
AB  - BACKGROUND: Flupirtine is a nonopioid, central analgesic without antipyretic or
      antiphlogistic properties. Flupirtine-MR is an oral modified-release formulation
      with a 100 mg fast-input and a 300 mg portion with slow protracted release.
      METHODS: Single- (D01) and repeated-dose (D03-D09) pharmacokinetics of 400 mg
      flupirtine-MR were investigated in patients with severe renal dysfunction (REN:
      N: 12; 21 50 years of age; creatinine clearance (CLCr)<=30 mL/min per 1.73 m2
      body surface area (BSA)) and healthy older subjects (EN1: N: 8; 60-69 years;
      CLCr>=80 mL/min and EN2: N: 8; >=70 years, CLCr>=60 mL/min) vs. young healthy
      control subjects (YN: N: 12; 21-40 years; CLCr>=90 mL/min). RESULTS: Renal
      dysfunction led to a relatively small average increase in systemic exposure to
      flupirtine: on D09, the REN : YN-ratios were 1.37 (95% confidence interval (CI):
      1.03-1.82), 1.21 (CI: 1.01-1.45), and 1.34 (CI: 1.09-1.64) for Css,0, Css,max,
      and Css,av, respectively. A similar increase in exposure was observed in older
      subjects: the respective EN1:YN-ratios were 1.30 (CI: 0.95-1.79), 1.23 (CI: 1.01
      1.49), and 1.23 (CI: 0.98-1.54); the EN2:YN-ratios were 1.50 (CI: 1.10-2.04),
      1.16 (CI: 0.85-1.41), and 1.41 (CI: 1.12-1.79), respectively. Neither age nor
      renal function was a predominant factor of pharmacokinetic variability. Single
      and repeated doses of flupirtine-MR were very well tolerated. CONCLUSIONS: The
      average renal and age effects were small, but the use of a lower starting dose
      (1/2 tablet) is recommended since some of these subjects might have relatively
      high exposure levels.

PMID- 25613540
TI  - Comparative assessment of determinants of health-related quality of life in
      hypertensive patients and normal population in south-west Nigeria.
AB  - OBJECTIVE: Health-related quality of life (HRQOL) in hypertensive patients may be
      influenced by the presence and the knowledge of disease, beliefs associated with
      the disease, blood pressure (BP) control, and drug utilization. The impact of
      hypertension on HRQOL in hypertensive patients compared to the normal population
      has not been assessed in Nigeria, the most populous country in sub-Saharan
      Africa. This study compares HRQOL in hypertensive patients and the normal
      population; the effect of BP control and medication on HRQOL of hypertensive
      patients is also assessed. MATERIALS AND METHODS: A prospective cross-sectional
      study of 713 individuals, 606 were hypertensive patients attending the University
      College Hospital in Oyo State, Nigeria, while 107 were normal persons residing in
      Ibadan. Data on sociodemographic status, clinical variables, and drug utilization
      were collected. World health organization-quality of life short version (WHO-QOL
      BREF) questionnaires were used to assess HRQOL of participants. RESULTS:
      Hypertensive patients had poorer HRQOL compared with normal individuals in the
      physical health (p<0.05), psychological (p<0.01), and total quality of life
      domains. Blood pressure control had no effect on HRQOL in domain (p>0.05). Drug
      use significantly worsened HRQOL of hypertensive patients in the psychological
      (p?0.01), social relationship (p<0.01), and the total quality of life domains
      (p<0.01). Multiple regression analysis showed that while income per month was
      positively predictive of physical, psychological, and total quality of life
      domains (r2=1.988, p=0.001; r2=3.710, p<0.001; r2=2.748, p<0.001), symptom count
      was negatively predictive of the same (r2=-0.746, p=0.005; r2=1.869, p<0.001; and
      r2=-1.094; p<0.001), respectively. Reduced symptoms and higher income improved
      quality of life in hypertensive patients. CONCLUSION: The presence of
      hypertension and antihypertensive medication reduced HRQOL of hypertensive
      patients, although BP control surprisingly did not impact HRQOL. However, lower
      symptom count and higher income improved quality of life.

PMID- 25613541
TI  - Pulmonary involvements of anti-neutrophil cytoplasmic autoantibody-associated
      renal vasculitis in Japan.
AB  - BACKGROUND: Pulmonary involvement is one of the hallmark lesions of anti
      neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) as well as
      rapidly progressive glomerulonephritis (RPGN). However, the pulmonary involvement
      of AAV patients seems to differ between Europe and Japan, as does the ANCA
      serotype. METHODS: This retrospective and prospective multicenter cohort study
      collected the clinical data of the features and outcomes of 1772 RPGN patients
      treated from 1989 to 2007 in Japan. Based on this nationwide RPGN survey, we
      analyzed the cases of 1147 AAV patients. RESULTS: We found that 52.3% of the AAV
      patients had pulmonary involvements: 15.4% of the AAV patients had alveolar
      hemorrhage (AH), 26.2% had interstitial lung disease (ILD), 2.8% had bronchial
      asthma, 2.4% had pulmonary granuloma and 12.8% had a chest X-ray abnormality
      without AH, ILD or pulmonary granuloma. Patient survival was significantly
      different among the following six groups: the 5-year survival rate was 41.5% in
      the patients with AH, 50.2% in those with ILD, 67.9% in those with bronchial
      asthma, 62.5% in those with pulmonary granuloma, 55.8% in those with chest X-ray
      abnormality and 73.3% in those without pulmonary involvement. AH was one of the
      predictors of 1- and 5-year mortality for patient survival in AAV, and ILD was
      added as one of the predictors of 5-year mortality. CONCLUSION: In these AAV
      patients, not only AH but also ILD was frequently observed. AH was associated
      with the prognosis, but ILD was associated with the long-term prognosis of AAV.

PMID- 25613542
TI  - The immune system in the normal endometrium and implications for endometrial
      cancer development.
AB  - Although described for the first time some decades ago, the contribution of the
      immune system to the establishment of tumors has not been extensively pursued for
      a long time. Over the last decade, however, more and more evidence has been
      accumulating concerning the role the immune system plays in tumor development and
      progression and its possible role in patient prognosis. In addition, interest is
      growing in preclinical and clinical research concerning the use of the immune
      system in the treatment of cancer. Immunotherapy for gynecological cancers in
      general, and for endometrial cancer in particular, is still in its infancy. Only
      a small number of studies, with varying success rates, have been published. Here,
      we provide a concise overview of the literature available on the role of the
      immune system in the normal endometrium and in endometrial cancer, in addition to
      the possible implications for future immunotherapeutic studies. 

PMID- 25613543
TI  - Slit2 withdrawal could contribute to the common inflammatory pathway leading to
      labor.

PMID- 25613544
TI  - Comparison of peer education and the classic training method for school aged
      children regarding smoking and its dangers.
AB  - The aim of the present study is to compare the knowledge levels acquired from two
      different methods of teaching (peer education and a classic training method)
      about smoking and its dangers to school aged children. This study was an
      experimental design with pre- and post-tests. A total of 354 students, 253 of
      whom were from the peer education school, and 101 of whom were from the classic
      training school, were included. The study results found that the mean post-test
      scores of the students in the peer education school were significantly increased,
      indicating a greater level of knowledge (p<.05). 

PMID- 25613545
TI  - Neonatal status epilepticus: differences between preterm and term newborns.
AB  - BACKGROUND: Despite the many studies on neonatal seizures, neonatal status
      epilepticus (NSE) remains a controversial entity, with no general consensus about
      its definition. We report the characteristics of newborns with NSE in order to
      assess whether they showed homogeneous features or displayed clinical and/or
      instrumental differences depending on gestational age (GA). Preterm and term
      neonates were compared and risk factors for adverse outcome evaluated. METHODS:
      From 154 newborns with video-EEG confirmed neonatal seizures admitted to the NICU
      of Parma University Hospital between January 1999 and December 2012, we collected
      a cohort of 47 newborns (19 preterm, 28 full-term) with NSE. NSE was defined as
      continuous seizure activity for at least 30 min or recurrent seizures lasting a
      total of 30 min without definite return to the baseline neurologic condition
      between seizures. Outcome was assessed at least at one year. We applied the
      chi(2) test to compare nominal data, and multivariate logistic regression
      analysis to determine independent risk factors for adverse outcome. RESULTS: Only
      Apgar scores and neurologic examination (p <= .02) were different between the
      groups. None of the preterm newborns had a favourable outcome compared to 25% of
      the full-term ones (p = .032). Moreover, 52.6% of preterm neonates died compared
      to 17.8% of the full-term newborns (p = .01; OR = 5.11). The only variable
      related to outcome was Apgar score at 5 min (p = .02). CONCLUSION: Newborns with
      NSE represented a quite homogeneous group regardless of the GA. Outcome was
      unfavourable in most of the subjects; however adverse outcome and death were more
      represented in preterm newborns.

PMID- 25613546
TI  - Memory-enhancing intra-basolateral amygdala clenbuterol infusion reduces post
      burst afterhyperpolarizations in hippocampal CA1 pyramidal neurons following
      inhibitory avoidance learning.
AB  - Activation of the basolateral amygdala can modulate the strength of fear
      memories, including those in single-trial inhibitory avoidance (IA) tasks. Memory
      retention, measured by the latency to re-enter a dark-compartment paired 24h
      earlier with a footshock, varies with intensity of this aversive stimulus. When
      higher intensity footshocks were used, hippocampal CA1 pyramidal neurons
      exhibited reduced afterhyperpolarizations (AHPs) 24h post-trial, an effect
      blocked by immediate post-trial inactivation of the basolateral complex of the
      amygdala (BLA). Similar AHP reductions in CA1 have been observed in a number of
      learning tasks, with time courses appropriate to support memory consolidation.
      When less intense footshocks were used for IA training of Sprague-Dawley rats,
      immediate post-trial infusion of the beta-adrenergic agonist clenbuterol into BLA
      was required to enhance hippocampal Arc protein expression 45 min later and to
      enhance memory retention tested 48 h later. Here, using Long-Evans rats and low
      intensity footshocks, we confirmed that bilateral immediate post-trial infusion
      of 15 ng/0.5 MUl of the beta-adrenergic agonist clenbuterol into BLA
      significantly enhances memory for an IA task. Next, clenbuterol was infused into
      one BLA immediately post-training, with vehicle infused into the contralateral
      BLA, then hippocampal CA1 neuron AHPs were assessed 24 h later. Only CA1 neurons
      from hemispheres ipsilateral to post-trial clenbuterol infusion showed learning
      dependent AHP reductions. Excitability of CA1 neurons from the same trained rats,
      but from the vehicle-infused hemispheres, was identical to that from untrained
      rats receiving unilateral clenbuterol or vehicle infusions. Peak AHPs, medium and
      slow AHPs, and accommodation were reduced only with the combination of IA
      training and unilateral BLA beta-receptor activation. Similar to previous
      observations of BLA adrenergic memory-related enhancement of Arc protein
      expression in hippocampus, increased CA1 neuronal excitability in the fear
      modulated IA task was activated by immediate post-trial beta-receptor activation
      of the ipsilateral BLA.

PMID- 25613548
TI  - Formate supplementation can increase nickel recovery by Halothiobacillus
      halophilus.
AB  - Acidophilic thiobacilli are traditional biotechnological agents for metal
      recovery from sulfide ores. Major industrial strains belong to autotrophic
      bacteria which are used without any organic supplements to stimulate the process.
      The autotrophic strain Acidithiobacillus ferrooxidans ATCC 21834 is known to use
      formate as a source of energy under special laboratory conditions. We showed the
      presence of formate dehydrogenase in the type strain of another autotrophic
      species Halothiobacillus halophilus representing another genus of thiobacilli.
      This finding prompted studies of bioleaching stimulation by formate. Canadian
      sulfide nickel ore was chosen for model investigation as leached substrate and
      the moderate acidophilic strain H. halophilus DSM 6132 was used as the leaching
      agent. In bench-scale bioleaching experiments, inoculation of the ore with H.
      halophilus supplemented with 0.3 % formate increased the recovery of nickel 70
      fold as compared with formate-free inoculation (1008.0 vs. 13.8 mg Ni/L per 34
      days). Bacteria H. halophilus belong to moderate acidophilic microorganisms;
      thus, the results were obtained with initial pH 7.4 and final pH 5.4. The
      mechanism of formate stimulation is under discussion.

PMID- 25613547
TI  - Spread of tumor microenvironment contributes to colonic obstruction through
      subperitoneal fibroblast activation in colon cancer.
AB  - We evaluated the influence of the cancer microenvironment formed by peritoneal
      invasion (CMPI) on clinical findings in colon cancer patients. In addition to the
      association with poor prognosis, we discovered a relationship with bowel
      obstruction. Detailed analysis revealed that clinical findings related to bowel
      obstruction occurred more frequently in patients with an elevated type tumor,
      which had peritoneal elastic laminal elevation to the tumor surface, compared to
      those with non-elevated type tumors among those with elastic laminal invasion
      (ELI). Lateral tumor spread and increase of tumor annularity rate in ELI-positive
      elevated type cases suggested the morphological progression from ELI-positive non
      elevated type to elevated type. In addition, alpha-smooth muscle actin expression
      was the highest in ELI-positive elevated type, and prominent expressions were
      found not only in the deep tumor area but also in the shallow tumor area.
      Furthermore, contraction assays revealed the robust contractile ability of
      subperitoneal fibroblasts stimulated by cancer cell-conditioned medium. Our
      findings suggest that CMPI spread into the luminal side of the colonic wall along
      with tumor progression, which caused bowel obstruction through the activation of
      subperitoneal fibroblasts. However, although the clinical outcome was not
      different between the two types, the clinical findings were affected by the
      spread of CMPI. We are the first to explore how the alteration of the tumor
      promoting microenvironment, along with tumor progression, contributes to the
      development of clinical findings. 

PMID- 25613549
TI  - Adrenal gland trauma: is extravasation an absolute indication for intervention?
AB  - BACKGROUND: Adrenal gland trauma (AGT) is potentially devastating if unrecognized
      during the treatment of trauma patients. Because of the adrenal glands' rich
      vascularity, they often hemorrhage upon traumatic impact. However, there has been
      no conclusion about the indications for intervention in cases of hemorrhage after
      AGT. METHODS: We conducted a prospective collection with a retrospective review
      in a Level I trauma center in Taiwan. This study enrolled all of the patients who
      suffered from AGT from May 2008 to May 2013. We retrieved and analyzed the
      patient demographic data, clinical presentation, AGT grade, injury severity
      score, management, hospital stay, and mortality. RESULTS: The cohort consisted of
      60 patients. The mean age was 31.0 +/- 15.9 years. There were 32 patients (53.3
      %) with extravasated AGT, which was associated with a high injury severity score,
      a high possibility of associated lung injury, and more than one accompanying
      trauma. Most of the patients could be treated conservatively. Five of these
      patients needed surgical hemostasis, and four of them needed angiographic
      embolization. Extravasation combined with a mean arterial pressure <70 mmHg was a
      predictor of the need for intervention (relative risk: 9.52, 95 % CI 1.64-55.56,
      p = 0.011). CONCLUSION: In conclusion, AGT is a rare injury with a good
      prognosis. Most AGT patients can be treated conservatively. Extravasation in AGT
      is not only a sign of hemorrhage, but also an indicator of severe associated
      injuries. However, extravasation in AGT does not always require further
      treatment. When intractable hypotension simultaneously occurs, further treatment
      should be considered.

PMID- 25613550
TI  - Comparison of retroperitoneoscopic and transperitoneal laparoscopic adrenalectomy
      for right-sided benign tumors: a single-institute experience.
AB  - INTRODUCTION: There is a lack of data regarding the appropriateness of
      transperitoneal and retroperitoneal approaches for right-sided laparoscopic
      adrenalectomy. The aim of this study was to determine whether there is any
      difference between right-sided transperitoneal laparoscopic adrenalectomy (TLA)
      and retroperitoneal laparoscopic adrenalectomy (RLA). MATERIAL AND METHODS: Our
      surgery database was reviewed to identify patients who underwent right-sided
      laparoscopic adrenalectomy with a retroperitoneal or transperitoneal approach
      since 2000. Fifty-five patients were enrolled (31 RLA and 24 TLA). Patient
      characteristics, as well as operative and perioperative details, were compared
      between the two groups. RESULTS: There was no difference in patient
      characteristics between the groups. There was a statistically significant
      difference (p=0.02) in blood loss (31.7+/-16.4 vs. 56.9+/-65.5 ml) between RLA
      and TLA when the patient's BMI was >26. There was no significant difference in
      operative time, conversion to open surgery, length of hospitalization, or time to
      oral intake between the groups. CONCLUSIONS: Right-sided laparoscopic
      adrenalectomy can be performed safely and effectively via either RLA or TLA.
      Surgeons can adopt either approach with confidence depending on their preference
      if they are familiar with that approach.

PMID- 25613551
TI  - Palladium versus platinum: the metal in the catalytic center of a molecular
      photocatalyst determines the mechanism of the hydrogen production with visible
      light.
AB  - To develop highly efficient molecular photocatalysts for visible light-driven
      hydrogen production, a thorough understanding of the photophysical and chemical
      processes in the photocatalyst is of vital importance. In this context, in situ X
      ray absorption spectroscopic (XAS) investigations show that the nature of the
      catalytically active metal center in a (N^N)MCl2 (M=Pd or Pt) coordination sphere
      has a significant impact on the mechanism of the hydrogen formation. Pd as the
      catalytic center showed a substantially altered chemical environment and a
      formation of metal colloids during catalysis, whereas no changes of the
      coordination sphere were observed for Pt as catalytic center. The high stability
      of the Pt center was confirmed by chloride addition and mercury poisoning
      experiments. Thus, for Pt a fundamentally different catalytic mechanism without
      the involvement of colloids is confirmed. 

PMID- 25613552
TI  - Aggressive and violent behavior among military personnel deployed to Iraq and
      Afghanistan: prevalence and link with deployment and combat exposure.
AB  - A systematic review and meta-analyses were conducted on studies of the prevalence
      of aggressive and violent behavior, as well as of violent offenses and
      convictions, among military personnel following deployment to Iraq and/or
      Afghanistan; the relationship with deployment and combat exposure; and the role
      that mental health problems, such as post-traumatic stress disorder (PTSD), have
      on the pathway between deployment and combat to violence. Seventeen studies
      published between January 1, 2001, and February 12, 2014, in the United States
      and the United Kingdom met the inclusion criteria. Despite methodological
      differences across studies, aggressive behavior was found to be prevalent among
      serving and formerly serving personnel, with pooled estimates of 10% (95%
      confidence interval (CI): 1, 20) for physical assault and 29% (95% CI: 25, 36)
      for all types of physical aggression in the last month, and worthy of further
      exploration. In both countries, rates were increased among combat-exposed,
      formerly serving personnel. The majority of studies suggested a small-to-moderate
      association between combat exposure and postdeployment physical aggression and
      violence, with a pooled estimate of the weighted odds ratio = 3.24 (95% CI: 2.75,
      3.82), with several studies finding that violence increased with intensity and
      frequency of exposure to combat traumas. The review's findings support the
      mediating role of PTSD between combat and postdeployment violence and the
      importance of alcohol, especially if comorbid with PTSD. 

PMID- 25613553
TI  - Epidemiologic approaches to veterans' health.
AB  - The present issue of Epidemiologic Reviews is dedicated to better understanding
      the health of men and women who have served in the military. There are 13
      articles that discuss a range of physical and mental health concerns among both
      military personnel who are currently serving and those who served in the past.
      The corresponding research provides insight into issues that are directly
      relevant and of keen interest to clinicians and investigators. The articles
      illustrate some of the obstacles to conducting rigorous epidemiologic research
      when seeking to inform the health issues of those who serve in the military and
      of veterans. Within the United States, they point to opportunities for the
      Department of Defense and Department of Veterans Affairs (VA) to address existing
      gaps in knowledge. The VA in particular can take advantage of its research
      infrastructure, altruistic veteran population, and clinical and administrative
      databases. In the era of multinational military interventions, international
      counterparts of the Department of Defense and VA should collaborate in the
      collection of data on relevant military exposures and also in the
      characterization of short- and long-term health effects related to service to
      better inform health needs. The work included in this issue is a call to the
      global research community to continue to invest resources to better characterize
      military service and its impact on health. Finally, these articles serve as a
      testament to the additional health burden carried by many of the women and men
      who have provided service to their country. 

PMID- 25613554
TI  - Metformin use in kidney transplant recipients in the United States: an
      observational study.
AB  - BACKGROUND/AIMS: Although metformin is contraindicated in patients with increased
      serum creatinine levels (>=1.5 mg/dl in men, >=1.4 mg/dl in women) in the United
      States, its use has not been systematically examined in kidney transplant
      recipients. We aimed to determine the frequency of metformin use and its
      associations among kidney transplant recipients, and to assess allograft and
      patient survival associated with metformin use. METHODS: In this retrospective
      cohort study, we linked Scientific Registry of Transplant Recipients data for all
      incident kidney transplants 2001-2012 and national pharmacy claims (n = 46,914).
      We compared recipients having one or more pharmacy claims for a metformin
      containing product (n = 4,609) and recipients having one or more claims for a non
      metformin glucose-lowering agent (n = 42,305). RESULTS: On average, metformin
      claims were filled later after transplant and were associated with higher
      estimated glomerular filtration rates before the first claim. Median serum
      creatinine (mg/dl) levels before the first claim were lower in recipients with
      metformin claims than in those with non-metformin claims (1.3 [interquartile
      range 1.0-1.7] vs. 1.6 [1.2-2.5], respectively; p < 0.0001). Metformin was
      associated with lower adjusted hazards for living donor (0.55, 95% confidence
      interval 0.38-0.80; p = 0.002) and deceased donor (0.55, 0.44-0.70; p < 0.0001)
      allograft survival at 3 years posttransplant, and with lower mortality.
      CONCLUSIONS: Despite metformin being contraindicated in renal dysfunction, many
      kidney transplant recipients receive it, and it is not associated with worse
      patient or allograft survival.

PMID- 25613555
TI  - Comparing the performance of Miscanthus x giganteus and wheat straw biomass in
      sulfuric acid based pretreatment.
AB  - The objective of this study was to assess and compare the suitability of
      Miscanthus x giganteus and wheat straw biomass in dilute acid catalyzed
      pretreatment. Miscanthus and wheat straw were treated in a dilute sulfuric
      acid/steam explosion pretreatment. As a result of combining dilute sulfuric acid-
      and steam explosion pretreatment the hemicellulose hydrolysis yields (96% in
      wheat straw and 90% in miscanthus) in both substrates were higher than reported
      in literature. The combined severity factor (=CSF) for optimal hemicellulose
      hydrolysis was 1.9 and 1.5 in for miscanthus and wheat straw respectively.
      Because of the higher CSF value more furfural, furfuryl alcohol, 5
      hydroxymethylfurfural and acetic acid was formed in miscanthus than in wheat
      straw pretreatment. 

PMID- 25613556
TI  - Moderate agreement between self-reported stroke and hospital-recorded stroke in
      two cohorts of Australian women: a validation study.
AB  - BACKGROUND: Conflicting findings on the validity of self-reported stroke from
      existing studies creates uncertainty about the appropriateness of using self
      reported stroke in epidemiological research. We aimed to compare self-reported
      stroke against hospital-recorded stroke, and investigate reasons for
      disagreement. METHODS: We included participants from the Australian Longitudinal
      Study on Women's Health born in 1921-26 (n = 1556) and 1946-51 (n = 2119), who
      were living in New South Wales and who returned all survey questionnaires over a
      defined period of time. We determined agreement between self-reported and
      hospitalised stroke by calculating sensitivity, specificity and kappa statistics.
      We investigated whether characteristics including age, education, area of
      residence, country of birth, language spoken at home, recent mental health at
      survey completion and proxy completion of questionnaire were associated with
      disagreement, using logistic regression analysis to obtain odds ratios (ORs) with
      95% confidence intervals (CIs). RESULTS: Agreement between self-report and
      hospital-recorded stroke was fair in older women (kappa 0.35, 95% CI 0.25 to
      0.46) and moderate in mid-aged women (0.56, 95% CI 0.37 to 0.75). There was a
      high proportion with unverified self-reported stroke, partly due to: reporting of
      transient ischaemic attacks; strokes occurring outside the period of interest;
      and possible reporting of stroke-like conditions. In the older cohort, a large
      proportion with unverified stroke had hospital records of other cerebrovascular
      disease. In both cohorts, higher education was associated with agreement, whereas
      recent poor mental health was associated with disagreement. CONCLUSION: Among
      women who returned survey questionnaires within the period of interest, validity
      of self-reported stroke was fair to moderate, but is probably underestimated.
      Agreement between self-report and hospital-recorded stroke was associated with
      individual characteristics. Where clinically verified stroke data are
      unavailable, self-report may be a reasonable alternative method of stroke
      ascertainment for some epidemiological studies.

PMID- 25613557
TI  - [Usefulness of Quantiferon-TB Gold in Tube(r) in screening for latent
      tuberculosis infection in health workers].
AB  - INTRODUCTION: Healthcare workers (HW) are considered a risk group for exposure to
      tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in
      all HW. The Tuberculin test (TT) has been used up until now for LTBI screening,
      but gives a high number of false positives, especially in patients vaccinated
      with BCG. Diagnostic methods based on detection of specific gamma interferon
      (IGRA) have recently appeared on the market in order to improve these drawbacks,
      but pose other dilemmas. The aim of this study is to determine the agreement
      between the two types of test and to carry out a cost-benefit study of the
      possible diagnostic strategies. MATERIAL AND METHODS: All newly hired HW by the
      Hospital Universitari Mutua Terrassa between January 2010 and October 2011 we
      were included in the study, as well as those who had their occupational review.
      Workers who been in contact with patients admitted with tuberculosis before the
      initial isolation were also tested. In all cases a parallel TT and serum
      QuantiFeron-TB Gold-in-Tube((r)) (QF-G-IT) assays were performed. TB disease was
      ruled out in all professional by chest X-ray. The TT was considered positive when
      it was equal to or more than 10mm and if the QF-G-IT was 0.35 IU/mL. A cost
      effectiveness analysis was designed with three possible strategies to detect LTBI
      in order to find the one with the best cost-benefit. RESULTS: A total of 226 HW
      were studied, with a mean age 30.65 +/- 16, of whom 44 (19.4%) had previous BCG
      vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%)
      cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both
      positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a
      negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa
      of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33,
      while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening
      strategies for LTBI diagnosis were those based on TT, but followed closely by the
      strategy based on TT with reconfirmation of positives with QF-G-IT. CONCLUSIONS:
      QF-G-IT seems to be a very sensitive technique to detect LTBI and allows false
      positives due to TT to be detected, particularly in BCG vaccinated HW. In this
      group QF-G-IT could be the ideal test to detect truly infected staff, and avoid
      unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in
      TT with reconfirmation or rejection of positive cases by QF-G-IT.

PMID- 25613558
TI  - [Incidence and lethality of invasive pneumococcal disease in Tarragona, Spain,
      2006-2009].
AB  - An epidemiological study was conducted on all cases of invasive pneumococcal
      disease (IPD) diagnosed in Tarragona, Spain, between 1 January 2006 and 31
      December 2009. A total of 286 IPD cases were observed, which was an overall
      incidence of 21.2 episodes per 100,000 persons-year (95% CI: 16.6-26.9).
      Incidence rates were 26.3/100,000 (95% CI: 14.4-44.3) among children,
      12.2/100,000 (95% CI: 8.2-17.6) among patients between 15-64 years and
      59.6/100,000 (95% CI: 40.0-85.8) in those >=65 years. Overall lethality rate was
      7.3% (none in children, 3.4% among patients 15-64 years, and 14.8% among patients
      >=65 years; p<0.001). 

PMID- 25613559
TI  - Timing of detection of anencephaly in The Netherlands.
AB  - OBJECTIVE: The objective of this study is to assess the gestational age at
      detection and prevalence of anencephaly in the North of The Netherlands over a 5
      year period. METHODS: A case list of all cases of anencephaly from two fetal
      medicine units was compiled. Cases were included if the estimated due date was
      between 1 August 2008 and 31 July 2013. RESULTS: Overall prevalence of
      anencephaly was 5.4 per 10.000 pregnancies (n = 110). The majority of cases (69%)
      was detected before 18 weeks' gestation. Factors determining successful early
      diagnosis were competence level of the sonographers, with a significantly higher
      detection rate when scans were performed by a sonographer licensed by the Fetal
      Medicine Foundation (FMF) for nuchal translucency measurement (p = 0.001), and
      gestational age at or beyond 11 weeks of gestation (p = 0.024). CONCLUSION:
      Improving detection of anencephaly in the first trimester requires ultrasound
      screening at or after 11 weeks of gestation, performed by experienced
      sonographers trained in recognizing fetal anomalies. Sonographers should be
      instructed that the goal of the first trimester scan is not only to measure
      nuchal translucency thickness but also to exclude major anomalies.

PMID- 25613560
TI  - Parasites and biological invasions: parallels, interactions, and control.
AB  - Species distributions are changing at an unprecedented rate owing to human
      activity. We examine how two key processes of redistribution - biological
      invasion and disease emergence - are interlinked. There are many parallels
      between invasion and emergence processes, and invasions can drive the spread of
      new diseases to wildlife. We examine the potential impacts of invasion and
      disease emergence, and discuss how these threats can be countered, focusing on
      biosecurity. In contrast with international policy on emerging diseases of humans
      and managed species, policy on invasive species and parasites of wildlife is
      fragmented, and the lack of international cooperation encourages individual
      parties to minimize their input into control. We call for international policy
      that acknowledges the strong links between emerging diseases and invasion risk. 

PMID- 25613562
TI  - Chemometric analysis for the evaluation of phenolic patterns in olive leaves from
      six cultivars at different growth stages.
AB  - Leaves from six important olive cultivars grown under the same agronomic
      conditions were collected at four different times from June to December and
      analyzed by high performance liquid chromatography-diode array detector-time-of
      flight-mass spectrometry (HPLC-DAD-TOF-MS). Twenty-eight phenolic compounds were
      identified and quantified. No qualitative differences were detected among leaves.
      However, for all cultivars, total concentrations of phenolic compounds decreased
      from June to August, then increased from October on, and reached higher levels
      again in December. Principal component analysis provided a clear separation of
      the phenolic content in leaves for different sampling times and cultivars. Hence,
      the availability of phenolic compounds depends on both the season and the
      cultivar. June and December seem to be good times to collect leaves as a source
      of phenolic compounds. December coincides with the harvest period of olives in
      the Andalusian region. Thus, in December olive leaves could be valorized
      efficiently as olive byproducts. 

PMID- 25613561
TI  - Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards
      thrombolytic therapy for cerebrovascular disorders-an overview and advancements.
AB  - Cerebral tissues possess highly selective and dynamic protection known as blood
      brain barrier (BBB) that regulates brain homeostasis and provides protection
      against invading pathogens and various chemicals including drug molecules. Such
      natural protection strictly monitors entry of drug molecules often required for
      the management of several diseases and disorders including cerebral vascular and
      neurological disorders. However, in recent times, the ischemic cerebrovascular
      disease and clinical manifestation of acute arterial thrombosis are the most
      common causes of mortality and morbidity worldwide. The management of cerebral
      Ischemia requires immediate infusion of external thrombolytic into systemic
      circulation and must cross the blood brain barrier. The major challenge with
      available thrombolytic is their poor affinity towards the blood brain barrier and
      cerebral tissue subsequently. In the clinical practice, a high dose of
      thrombolytic often prescribed to deliver drugs across the blood brain barrier
      which results in drug dependent toxicity leading to damage of neuronal tissues.
      In recent times, more emphasis was given to utilize blood brain barrier transport
      mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses
      a series of receptor on membrane became an ideal target for selective drug
      delivery. In this review, the author has given more emphasis molecular biology of
      receptor on blood brain barrier and their potential as a carrier for drug
      molecules to cerebral tissues. Further, the use of nanoscale design and real-time
      monitoring for developed therapeutic to encounter drug dependent toxicity has
      been reviewed in this study.

PMID- 25613563
TI  - Mechanisms of protection against diabetes-induced impairment of endothelium
      dependent vasorelaxation by Tanshinone IIA.
AB  - BACKGROUND: Impairment of endothelium-dependent vasorelaxation has been suggested
      to play a principle role of endothelial dysfunction in the development of
      cardiovascular complications of diabetes. Recent studies have demonstrated a
      protective effect of Tanshinone IIA (Tan) on endothelial nitric oxide synthase
      (eNOS)-NO pathway. However, its role in endothelium-dependent vasorelaxation in
      diabetes and precise mechanisms remain elusive. METHODS: Sprague-Dawley rats were
      injected intraperitoneally with streptozotocin (STZ) to induce diabetes and then
      administered orally with Tan for 2 weeks. For the in vitro study, human umbilical
      vein endothelial cells (HUVECs) were co-incubated with Tan and high glucose for
      48 h. RESULTS: eNOS expression and NO generation were significantly decreased in
      diabetic rats. These decreases were accompanied by an impairment of endothelium
      dependent relaxation. Administration of Tan ameliorated the aberrant changes in
      eNOS expression, NO generation and endothelium-dependent relaxation in diabetic
      rats. Expectedly, Tan also inhibited high glucose-induced decrease of eNOS
      expression and NO generation in a concentration-dependent manner in HUVECs.
      Mechanistically, high glucose attenuated eNOS transcriptional activity through
      inhibiting the binding activity and nuclear translocation of Sp1 and AP-1.
      However, Tan did not prevent these effects. At post-transcriptional level, Tan
      increased eNOS expression and activity through multiple mechanisms including
      regulation of mRNA and protein half-life, degradation, coupling and serine 1177
      phosphorylation. Rather than affecting protein phosphatase 2A (PP2A) expression
      and activity, Tan markedly inhibited the translocation of PP2A-A from cytosol to
      membrane and subsequently impaired PP2A-A/eNOS interaction, leading to prevent
      eNOS dephosphorylation. All these alterations underlie the protective role of Tan
      on eNOS expression following high glucose stimulation. CONCLUSIONS: Our data
      demonstrate that high glucose decreases eNOS expression initiating at a
      transcriptional level, whereas Tan prevents such effect through multiple ways of
      post-transcriptional mechanism. GENERAL SIGNIFICANCE: Our work provided novel
      mechanisms for Tan in regulating vasorelaxation and may help to better understand
      the cardiovascular protective action of Tan.

PMID- 25613564
TI  - Intestinal dysbiosis: an emerging cause of pregnancy complications?
AB  - The gut microbiota is intimately involved in numerous aspects of normal human
      physiology, including nutrition and metabolism, immunomodulation and behavior and
      stress response. Intestinal dysbiosis can be a contributing cause of many
      diseases, altering the function of both near and far organ systems. During
      pregnancy, the maternal body undergoes dramatic physiological changes to support
      the growth of fetus-placenta, while intestinal dysbiosis may directly or
      indirectly disturb the remodeling of physiological balance, leading to maternal
      maladaptation. Thus, intestinal dysbiosis, i.e., altered composition or
      metabolism of microbiota may adversely affect pregnancy outcome and lead to
      pregnancy complications via disrupting maternal adaptation. Indeed, pregnant
      women with potential maladaptations are at high risk of developing pregnancy
      disorders, which is increasingly observed in clinical cases. Here we discuss the
      hypothesis that intestinal dysbiosis may induce pregnancy complications via
      affecting maternal adaptation and the possible mechanistic pathways. 

PMID- 25613565
TI  - Autologous Hematopoietic Stem Cells transplantation and genetic modification of
      CCR5 m303/m303 mutant patient for HIV/AIDS.
AB  - HIV and AIDS is one of the biggest challenges all over the world. There are an
      approximately 34 million people living with the virus, and a large number of them
      become infected each year. Although there are some antiviral drugs for HIV viral
      load reduction, they are not sufficient. There is no cure for AIDS. Nowadays
      natural resistance or immunity has absorbed attentions. Because in some HIV
      positive patients progression trend is slow or even they indicate resistance to
      AIDS. One of the most interesting approaches in this category is CCR5 gene. CCR5
      is a main cc-chemokine co-receptor that facilitates HIV-1 entry to macrophage and
      CD4(+) T cells. To now, many polymorphisms have been known by CCR5 gene that
      produces a truncated protein with no function. So, HIV-1 could not entry to
      immune-cells and the body resistant to HIV/AIDS. Delta32/Delta32 and m303/m303
      homozygotes are example of mutations that could create this resistance mechanism.
      There is a new treatment, such as Hematopoietic Stem Cell transplantation (HSCT)
      in Berlin and Boston patients for Delta32/Delta32 mutation. It could eliminate co
      receptor antagonist and highly-active-anti retroviral therapy (HAART) drugs
      problems such as toxicity, low safety and side-effects. Now there, the aim of
      this hypothesis will be evaluation of a new mutation CCR5 m303/m303 as autologous
      HSCT. This novel hypothesis indicates that autologous HSCT for m303/m303 could be
      effective treatment for anyone HIV/AIDS affected patient worldwide. 

PMID- 25613566
TI  - Beneficial effects of cellular autofluorescence following ionization radiation:
      hypothetical approaches for radiation protection and enhancing radiotherapy
      effectiveness.
AB  - Ionization radiation (IR) is a main part of modern technologies with a double
      edge sword manner. Finding the most feasible therapies to reduce adverse effects
      of IR and also enhancing radiotherapy effectiveness is a debating issue that has
      been challenged and studied for years. The main aim of the present hypothetical
      research was to theorize and suggest a new biological radiation protection
      approach and also increasing radiotherapy outcomes based on cellular
      autofluorescence following IR. In this hypothesis, we suggested that this
      cellular autofluorescence can activate some synthetic drugs called photo
      activated agents that are injected in human body after radiation exposures
      scenarios. Photo activated agents can activate biological pathways such as DNA
      repair and immunostimulation pathways, bystander signals blocking, and so survive
      cells and tissues. In the other hand, light emitted by cellular response to
      radiation can be used as like as photodynamic therapy and therefore more cancer
      cells killing via apoptosis and necrosis. These ideas can be performed in future
      using more animal and in vivo/in vitro studies and clinical trials. In
      conclusion, cellular autofluorescence after radiation exposure can be used as a
      source for activation specific drugs for radiation protection and also radiation
      therapy effectiveness. These hypothetical therapeutic approaches can be served as
      personalized therapy based on individual radiosensitivity. 

PMID- 25613567
TI  - Vitamin K: the missing link to prostate health.
AB  - Though age-related prostate enlargement is very common in Western societies, and
      the causes of benign prostate hyperplasia, BPH, have been diligently sought
      after, there is no biological, mechanistic explanation dealing with the root
      causes and progression of this very common disorder among men. All treatments to
      date are based on symptomatic relief, not a fundamental understanding of the
      cause of the disease. However, recent advances have shown that even subclinical
      varicoceles, which are more common than generally realized, cause retrograde
      blood flow from the testes past the prostate gland causing over a 130-fold
      increase in free testosterone in the veins near the prostate. By treating the
      varicoceles via embolization of the internal spermatic vein and its communicating
      and connected vessels the prostate enlargement can be reversed with corresponding
      symptomatic relief. So, varicose veins in the pampiniform venous plexus,
      varicoceles, are the direct cause of BPH. But what causes varicoceles? Recent
      research has uncovered the role of vitamin K in the calcification of varicose
      veins as well as a role in the proliferation of smooth muscle cells in the media
      layer of the vein wall. Vitamin K is intimately involved in the formation of
      varicose veins. The hypothesis is that poor prostate health is essentially a
      vitamin K insufficiency disorder. By providing vitamin K in the right form and
      quantity, along with other supporting nutrients and phytochemicals, it is likely
      that excellent prostate health can be extended much longer, and perhaps poor
      prostate health can be reversed. A protective role for vitamin K with respect to
      advanced prostate cancer was already found in the Heidelberg cohort of the EPIC
      study. This hypothesis can be further evaluated in studies examining the
      connection between vitamin K and varicoceles, and also by examining the
      connection between varicoceles and benign prostate hyperplasia. If this
      hypothesis is found to be true, management of prostate health will be radically
      altered. Rather than focusing on prostate health as a hormonal imbalance,
      prostate enlargement will be seen as a result of poor health of the veins in
      general and the internal spermatic veins in particular. Factors which promote the
      health of the veins will become a greater focus of research, including the role
      of vitamin K. Finally, the emerging understanding of the cause of BPH will
      empower men to take care of their bodies so they can enjoy much better health
      through their entire lifespan. 

PMID- 25613568
TI  - GP pilots are "last chance saloon" for care.data scheme.

PMID- 25613570
TI  - Occipital post-traumatic intradiploic arachnoid cyst converted to
      pseudomeningocele after re-trauma: a rare complication of rare pathology.
AB  - BACKGROUND: Growing skull fracture (GSF)/pseudomeningocele is a rare complication
      of head injury in children. Post-traumatic intradiploic arachnoid cyst (PTIAC) is
      a variant but it is extremely rare. PTIACs are usually asymptomatic or with mild
      symptoms like headache. The rupture of PTIAC due to re-trauma leading to
      pseudomeningocele formation has not been seen or reported before. PATIENT AND
      METHOD: We present a case of occipital PTIAC where pseudomeningocele developed
      after re-trauma, and discuss the pathogenesis and management. RESULT: En masse
      removal of the ruptured PTIAC was performed along with dural-defect repair. The
      post-operative recovery was good. CONCLUSION: PTIAC is an extremely rare
      occurrence as a variant of GSF. It is usually asymptomatic, but it may rupture
      with trivial trauma due to a thinned-out outer table and then converts into
      pseudomengocele. En masse excision with dural-defect repair gives good results in
      cases of ruptured PTIAC due to re-trauma.

PMID- 25613569
TI  - Electrostatic doping as a source for robust ferromagnetism at the interface
      between antiferromagnetic cobalt oxides.
AB  - Polar oxide interfaces are an important focus of research due to their novel
      functionality which is not available in the bulk constituents. So far, research
      has focused mainly on heterointerfaces derived from the perovskite structure. It
      is important to extend our understanding of electronic reconstruction phenomena
      to a broader class of materials and structure types. Here we report from high
      resolution transmission electron microscopy and quantitative magnetometry a
      robust - above room temperature (Curie temperature TC ? 300 K) - environmentally
      stable- ferromagnetically coupled interface layer between the antiferromagnetic
      rocksalt CoO core and a 2-4 nm thick antiferromagnetic spinel Co3O4 surface layer
      in octahedron-shaped nanocrystals. Density functional theory calculations with an
      on-site Coulomb repulsion parameter identify the origin of the experimentally
      observed ferromagnetic phase as a charge transfer process (partial reduction) of
      Co(3+) to Co(2+) at the CoO/Co3O4 interface, with Co(2+) being in the low spin
      state, unlike the high spin state of its counterpart in CoO. This finding may
      serve as a guideline for designing new functional nanomagnets based on oxidation
      resistant antiferromagnetic transition metal oxides.

PMID- 25613571
TI  - Cationic nanocarriers induce cell necrosis through impairment of Na(+)/K(+)
      ATPase and cause subsequent inflammatory response.
AB  - Nanocarriers with positive surface charges are known for their toxicity which has
      limited their clinical applications. The mechanism underlying their toxicity,
      such as the induction of inflammatory response, remains largely unknown. In the
      present study we found that injection of cationic nanocarriers, including
      cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic
      cells. Cell necrosis induced by cationic nanocarriers is dependent on their
      positive surface charges, but does not require RIP1 and Mlkl. Instead,
      intracellular Na(+) overload was found to accompany the cell death. Depletion of
      Na(+) in culture medium or pretreatment of cells with the Na(+)/K(+)-ATPase
      cation-binding site inhibitor ouabain, protected cells from cell necrosis.
      Moreover, treatment with cationic nanocarriers inhibited Na(+)/K(+)-ATPase
      activity both in vitro and in vivo. The computational simulation showed that
      cationic carriers could interact with cation-binding site of Na(+)/K(+)-ATPase.
      Mice pretreated with a small dose of ouabain showed improved survival after
      injection of a lethal dose of cationic nanocarriers. Further analyses suggest
      that cell necrosis induced by cationic nanocarriers and the resulting leakage of
      mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by
      a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal
      a novel mechanism whereby cationic nanocarriers induce acute cell necrosis
      through the interaction with Na(+)/K(+)-ATPase, with the subsequent exposure of
      mitochondrial damage-associated molecular patterns as a key event that mediates
      the inflammatory responses. Our study has important implications for evaluating
      the biocompatibility of nanocarriers and designing better and safer ones for drug
      delivery. 

PMID- 25613573
TI  - Pneumococcal vaccination during pregnancy for preventing infant infection.
AB  - BACKGROUND: Approximately 450,000 children worldwide die of pneumococcal
      infections each year. The development of bacterial resistance to antimicrobials
      adds to the difficulty of treatment of diseases and emphasizes the need for a
      preventive approach. Newborn vaccination schedules could substantially reduce the
      impact of pneumococcal disease in immunized children, but do not have an effect
      on the morbidity and mortality of infants less than three months of age.
      Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal
      disease during the first months of life before the pneumococcal vaccine
      administered to the infant starts to produce protection. OBJECTIVES: To assess
      the effect of pneumococcal vaccination during pregnancy for preventing infant
      infection. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (31 July 2014) and reference lists of retrieved studies.
      SELECTION CRITERIA: Randomized controlled trials in pregnant women comparing
      pneumococcal vaccine with placebo or doing nothing, or with another vaccine to
      prevent infant infections. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion and risk of bias, extracted data and
      checked them for accuracy. We contacted study authors for additional information.
      MAIN RESULTS: Seven trials were included, but only six trials (919 participants)
      contributed data. There was no evidence that pneumococcal vaccination during
      pregnancy reduces the risk of neonatal infection (risk ratio (RR) 0.66; 95%
      confidence interval (CI) 0.30 to 1.46; two trials, 241 pregnancies, low quality
      evidence). Although the data suggest an effect in reducing pneumococcal
      colonization in infants by 16 months of age (average RR 0.33; 95% CI 0.11 to
      0.98; one trial, 56 pregnancies), there was no evidence of this effect in infants
      at two to three months of age (average RR 1.13; 95% CI 0.46 to 2.78; two trials,
      146 pregnancies, low quality evidence) or by six to seven months of age (average
      RR 0.67, 95% CI 0.22 to 2.08; two trials, 148 pregnancies, low quality evidence).
      None of the trials included in this review reported neonatal death as a result of
      pneumococcal infection.Neonatal antibody levels were reported as geometric mean
      and 95% CI. There were inconsistent results between studies. Two studies showed
      significantly higher immunoglobulin G (IgG) levels in cord blood in the
      pneumococcal vaccine group when compared with the control group for all
      serotypes. In contrast, another trial showed no difference in neonatal antibody
      levels between the pneumococcal vaccine group and the control group.Maternal
      antibody levels were also reported as geometric mean and 95% CI. One study showed
      significantly higher IgG levels in maternal serum in women immunized with
      pneumococcal vaccine when compared with control vaccine regardless of any
      serotypes. Another study showed significantly higher maternal antibody levels
      only for serotype 14, but no evidence of an effect for other serotypes.The
      percentage of women with seroprotection was measured in one trial at delivery and
      at 12 months post-delivery. At delivery, results favored the intervention group
      for serotype 6 (RR 1.49, 95% CI 1.31 to 1.69), serotype 14 (RR 1.40, 95% CI 1.25
      to 1.56) and serotype 19 (RR 2.29, 95% CI 1.89 to 2.76). There were no group
      differences seen at 12 months post-delivery for serotypes 6 or 14 (RR 1.06, 95%
      CI 1.00 to 1.12 and RR 1.06, 95% CI 0.98 to 1.15, respectively), but results
      favored the intervention group for serotype 19 (RR 1.59, 95% CI 1.37 to 1.85).No
      significant difference for tenderness at the injection site between women who
      received pneumococcal vaccine and those who received control vaccine (average RR
      3.20; 95% CI 0.32 to 31.54; two trials, 130 women).The overall quality of
      evidence is low for primary outcomes. Most outcomes had wide confidence intervals
      crossing the line of no effect, and most of the included trials had small numbers
      of participants and few events which led to downgrading evidence for imprecision
      of findings. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess
      whether pneumococcal vaccination during pregnancy could reduce infant infections.

PMID- 25613572
TI  - Structural insights into Rhino-mediated germline piRNA cluster formation.

PMID- 25613574
TI  - Premarital screening for hemoglobinopathies: experience of a single center in
      Kurdistan, Iraq.
AB  - BACKGROUND: A program for the prevention of major hemoglobinopathies was
      initiated in 2008 in the Kurdistan region of Iraq. This study reports on the
      achievements and challenges of the program. METHODS: A total of 102,554
      individuals (51,277 couples) visiting a premarital center between 2008 and 2012
      were screened for carrier status of hemoglobinopathies, and at-risk couples were
      counseled. RESULTS: A total of 223 (4.3/1,000) couples were identified and
      counseled as high-risk couples. Available data on 198 high-risk couples indicated
      that 90.4% proceeded with their marriage plans, and 15% of these married couples
      decided to have prenatal diagnosis (PND) in subsequent pregnancies with the
      identification of 8 affected fetuses; all were terminated as chosen by the
      parents. Thirty affected births were recorded among the high-risk couples. The
      premarital program managed to reduce the affected birth rate of major
      hemoglobinopathies by 21.1%. Of the 136 affected babies born during the study
      period, 77.9% were born to couples married prior to the start of the program,
      while 22.1% were born to couples identified as having a high risk. The main
      reason for not taking the option of PND was unaffordable costs. CONCLUSIONS:
      Financial support would have increased opting for PND by high-risk couples.
      Further reduction in affected birth rates could be achieved by including parallel
      antenatal screening programs to cover those married before the initiation of the
      premarital program and improving the public health education and counseling
      programs.

PMID- 25613575
TI  - Bladder rupture - a rare complication of extraperitoneal balloon dissection
      during robot-assisted radical prostatectomy.
AB  - INTRODUCTION: Balloon dissection to create the extraperitoneal space to
      facilitate laparoscopic procedures is generally a safe step. However,
      complications can include vascular and visceral injuries. Bladder injury during
      balloon dilation of extraperitoneal space has previously been described during
      herniorraphy. This is the first reported case of bladder injury during balloon
      dilation of the extraperitoneal space during robot-assisted radical
      prostatectomy. METHODS: We report transection of bladder at the prostato-vesical
      junction, during balloon dilation of extraperitoneal space, in a 66-year-old man
      undergoing extraperitoneal robot-assisted radical prostatectomy. RESULTS: The
      patient had an uneventful procedure due to immediate recognition of this intra
      operative complication. At 6-month follow-up, he reports complete return of
      urinary continence and is free from biochemical recurrence from prostate cancer.
      DISCUSSION: Albeit uncommon, balloon-related complications can occur. Surgeons
      performing extraperitoneal laparoscopic procedures should be aware of the range
      of potential complications specifically related to balloon dilation of
      extraperitoneal space. With experience, these complications can be mitigated.

PMID- 25613577
TI  - Controlling porosity in lignin-derived nanoporous carbon for supercapacitor
      applications.

PMID- 25613578
TI  - In vivo EPR on spin labeled colicin A reveals an oligomeric assembly of the pore
      forming domain in E. coli membranes.
AB  - We report on the application of site-directed spin labeling (SDSL) and electron
      paramagnetic resonance (EPR) spectroscopy to study possible oligomerization of
      the bacterial toxin colicin A (ColA) upon membrane insertion in vitro and in
      vivo. We applied SDSL-EPR protocols and optimized experimental conditions to
      perform continuous wave EPR experiments and double electron-electron resonance
      distance measurements on intact Escherichia coli cells interacting with nitroxide
      spin-labeled ColA. Our data suggest that ColA forms dimers upon membrane
      insertion, thus explaining previously reported pore diameters of about 1 nm,
      which are unlikely to be formed by a single colicin A monomer. 

PMID- 25613576
TI  - Personalized therapeutic strategies for patients with retinitis pigmentosa.
AB  - INTRODUCTION: Retinitis pigmentosa (RP) encompasses many different hereditary
      retinal degenerations that are caused by a vast array of different gene mutations
      and have highly variable disease presentations and severities. This heterogeneity
      poses a significant therapeutic challenge, although an answer may eventually be
      found through two recent innovations: induced pluripotent stem cells (iPSCs) and
      clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome
      editing. AREAS COVERED: This review discusses the wide-ranging applications of
      iPSCs and CRISPR-including disease modelling, diagnostics and therapeutics - with
      an ultimate view towards understanding how these two technologies can come
      together to address disease heterogeneity and orphan genes in a novel
      personalized medicine platform. An extensive literature search was conducted in
      PubMed and Google Scholar, with a particular focus on high-impact research
      published within the last 1 - 2 years and centered broadly on the subjects of
      retinal gene therapy, iPSC-derived outer retina cells, stem cell transplantation
      and CRISPR/Cas gene editing. EXPERT OPINION: For the retinal pigment epithelium,
      autologous transplantation of gene-corrected grafts derived from iPSCs may well
      be technically feasible in the near future. Photoreceptor transplantation faces
      more significant unresolved technical challenges but remains an achievable, if
      more distant, goal given the rapid pace of advancements in the field.

PMID- 25613579
TI  - Insect vision models under scrutiny: what bumblebees (Bombus terrestris
      terrestris L.) can still tell us.
AB  - Three contending models address the ability of bees to detect and discriminate
      colours: the colour opponent coding (COC) model, the colour hexagon (CH) model
      and the receptor noise-limited (RN) model, but few studies attempt to determine
      which model fits experimental data best. To assess whether the models provide an
      accurate description of bumblebee colour space, we trained bees to discriminate
      four colour pairs. The perceptual distance between the colours of each pair was
      similar according to the CH model but varied widely according to the COC and RN
      models. The time that bees required to select a flower and the proportion of
      correct choices differed between groups: decision times decreased as achromatic
      contrast increased, and the proportion of correct choices increased with
      achromatic contrast and perceptual distance, as predicted by the COC and RN
      models. These results suggest that both chromatic and achromatic contrasts
      affected the discriminability of colour pairs. Since flower colour affects the
      foraging choices of bees and foraging choices affect the reproductive success of
      plants, a better understanding of which model is more accurate under each
      circumstance is required to predict bee behaviour and the ecological implications
      of flower choice and colour. 

PMID- 25613580
TI  - A dysregulated microRNA-26a/EphA2 axis impairs endothelial progenitor cell
      function via the p38 MAPK/VEGF pathway.
AB  - BACKGROUND: Dysfunction of circulating endothelial progenitor cells (EPCs) is
      associated with the onset of cardiovascular disorders. Circulating microRNAs
      (miRNAs) have been recognized as novel biomarkers and potential therapeutic
      targets. Here, we examined the role of miR-26a overexpression in atherosclerosis
      and explored the underlying mechanisms. METHODS: EPCs were obtained from patients
      with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were
      exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2
      and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF
      levels were determined by enzyme linked immunosorbent assay. Cell viability was
      assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a
      target of miR-26a. RESULTS: MiR-26a was overexpressed in patients with
      atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a
      direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and
      impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and
      reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown
      modulated the activity of p38 MAPK and the levels of VEGF in EPCs. CONCLUSIONS:
      The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a
      mechanism involving the p38 MAPK/VEGF pathway.

PMID- 25613581
TI  - Male circumcision for protection against HIV infection in sub-Saharan Africa: the
      evidence in favour justifies the implementation now in progress.
AB  - This article responds to a recent 'controversy study' in Global Public Health by
      de Camargo et al. directed at three randomised controlled trials (RCTs) of male
      circumcision (MC) for HIV prevention. These trials were conducted in three
      countries in sub-Saharan Africa (SSA) and published in 2005 and 2007. The RCTs
      confirmed observational data that had accumulated over the preceding two decades
      showing that MC reduces by 60% the risk of HIV infection in heterosexual men.
      Based on the RCT results, MC was adopted by global and national HIV policy-makers
      as an additional intervention for HIV prevention. Voluntary medical MC (VMMC) is
      now being implemented in 14 SSA countries. Thus referring to MC for HIV
      prevention as 'debate' and viewing MC through a lens of controversy seems
      mistaken. In their criticism, de Camargo et al. misrepresent and misinterpret
      current science supporting MC for HIV prevention, omit previous denunciations of
      arguments similar to theirs, and ignore evidence from ongoing scientific
      research. Here we point out the flaws in three areas de Camargo et al. find
      contentious. In doing so, we direct readers to growing evidence of MC as an
      efficacious, safe, acceptable, relatively low-cost one-off biomedical
      intervention for HIV prevention.

PMID- 25613582
TI  - Protective effect of selenium against aluminum chloride-induced Alzheimer's
      disease: behavioral and biochemical alterations in rats.
AB  - In present study, selenium was selected for evaluating effect of selenium on
      aluminum chloride (AlCl3)-induced Alzheimer's disease in rats. Thirty Wistar rats
      were divided into five groups of six in each. Group I (control) received
      distilled water, group II-AlCl3 (100 mg/kg, p.o.), group III-selenium (1 mg/kg,
      p.o.), group IV-AlCl3 + vitamin E (100 mg/kg, p.o. + 100 mg/kg, p.o.), and group
      V-AlCl3 + selenium (100 mg/kg, p.o. + 1 mg/kg, p.o.) for 21 days. At end of
      experiment, various behavioral, biochemical, and histopathological assessments
      were carried out. The animals showed increase in time to reach platform in Morris
      water maze and decreased step-down latencies in passive avoidance test indicating
      learning and memory impairment in aluminum chloride-treated group, but
      administration of selenium decreased time to reach platform in Morris water maze,
      increased step-down latencies, and strengthened its memory action in drug-treated
      animals. There was decrease in muscle strength measured by rotarod test
      indicating motor incoordination and decrease in locomotor activity assessed by
      actophotometer test in AlCl3 control group, whereas in selenium-AlCl3 group,
      there was improvement in muscle strength and locomotion. Biochemical analysis of
      the brain revealed that chronic administration of AlCl3 significantly increased
      lipid peroxidation and decreased levels of acetyl cholinesterase, catalase,
      reduced glutathione and glutathione reductase, an index of oxidative stress
      process. Administration of selenium attenuated lipid peroxidation and ameliorated
      the biochemical changes. There were marked changes at subcellular level observed
      by histopathology studies in AlCl3 group, and better improvement in these changes
      was observed in selenium + AlCl3group. Therefore, this study strengthens the
      hypothesis that selenium helps to combat oxidative stress produced by
      accumulation of AlCl3 in the brain and helps in prophylaxis of Alzheimer's
      diseases.

PMID- 25613583
TI  - Serum magnesium, iron and ferritin levels in patients with diabetic retinopathy
      attending Makkah Eye Complex, Khartoum, Sudan.
AB  - Diabetic retinopathy is the most common complications of diabetes mellitus that,
      in most occasions, lead to blindness. Multiple evidences linked the serum
      magnesium, iron and ferritin disturbance with diabetes and its complications. A
      case-control study was conducted at Makkah Eye Complex, Khartoum, Sudan, to
      compare the levels of serum magnesium, iron and ferritin in patients with
      diabetic retinopathy with diabetic patients without diabetic retinopathy
      (controls). Findings indicate that all patients had type 2 diabetes. The two
      groups (50 in each arm) were well matched in their basic characteristics. Median
      (25th-75th interquartile) of serum magnesium in patients with diabetic
      retinopathy were significantly lower than patients without diabetic retinopathy
      [1.48 (0.75-1.64) vs. 1.92 (1.4-2.3)mg/dl, P = 0.022]. The median of serum iron
      and ferritin were lower in cases than control group but did not reach a
      statistical significance [20.5 (17.2-48.0) vs. 27.0 (16.0-54.0) MUg/dl, P =
      0.568; 98.0 (45.0-134.75) vs. 101.0 (47.0-161.0) MUg/l, P = 0.818]. The duration
      of diabetes [16.5 (9.3) vs. 11.2 (6.6) years; P = 0.014] and haemoglobin level
      [13.7 (0.9) vs. 12.5 (2.0) g/dl; P = 0.039] were significantly higher in cases
      group than control group. A significant inverse correlation was observed between
      serum magnesium and iron levels. Twenty (40 %) patients had severe non
      proliferative diabetic retinopathy with mild macular edema, which is the most
      prevalent type among the cases group. Hypomagnesaemia among diabetic patients was
      associated with diabetic retinopathy, while serum iron and ferritin have no
      significant effect in this setting. Severe non-proliferative diabetic retinopathy
      with mild macular edema is the prevalent type in this study.

PMID- 25613584
TI  - Study of trace elements in liver cirrhosis patients and their role in prognosis
      of disease.
AB  - The objectives of this study are to evaluate trace elements in patients with
      liver cirrhosis and to assess their association with severity of the disease. One
      hundred fifty cirrhotic subjects of either sex ranging in age from 20-70 years
      were included in the study, and the results were compared with 50 age- and sex
      matched healthy control subjects. All cirrhotic subjects were assessed for
      severity of disease as mild (Child A), moderate (Child B), and severe (Child C)
      as per Child-Pugh classification. Routine investigations were done and trace
      elements (Cu, Zn, Se, and Mg) were analyzed on atomic absorption
      spectrophotometer. Serum level of copper was found significantly increased in
      patients with liver cirrhosis as compared to control group. Whereas serum zinc,
      selenium, and magnesium levels were significantly decreased in cirrhotic subjects
      as compared to controls. Trace elements were compared with severity of liver
      cirrhosis. Serum copper concentration was slightly increased in patients with
      more severe clinical state of liver cirrhosis; however, mean level difference of
      copper among the Child-Pugh groups were statistically not significant. Moreover,
      there was no significant correlation between copper and Child-Pugh Score.
      However, copper showed a significant negative correlation with zinc. Serum zinc,
      magnesium, and selenium levels were significantly decreased with advancement of
      liver disease as compared to early stage of liver cirrhosis and showed a
      significant negative correlation with Child-Pugh Score. Trace element
      abnormalities may reflect the condition of liver dysfunction. These results
      suggest that liver dysfunction may alter the metabolism of trace elements. Our
      study shows that micronutrients status in liver cirrhosis correlates well with
      severity of liver cirrhosis. Micronutrients supplementation in liver cirrhotic
      patients may prevent progression of disease and development of complications;
      however, further research needs to be done.

PMID- 25613586
TI  - The Use of the Developmental Rate of the Aquatic Midge Chironomus riparius
      (Diptera, Chironomidae) in the Assessment of the Postsubmersion Interval.
AB  - Nonbiting midges (Diptera, Chironomidae) are the most abundant members of the
      fauna associated with submerged carcasses, but their use in the medicolegal
      context is very restricted because of their complex ontogeny. In this case, the
      corpse of a woman was recovered in late spring from a river in Granada (Iberian
      Peninsula). It showed obvious signs of long permanence in the aquatic environment
      and, along with pulmonary and microscopical analyses, led to the conclusion that
      the cause of death was drowning. Several larvae-like specimens were sampled from
      the scalp and later identified by morphological external features as IV instar
      larvae of Chironomus riparius Meigen, 1804 (Diptera, Chironomidae). Sequencing of
      cytochrome oxidase subunit I was performed to confirm the identification. The
      knowledge of the biology of C. riparius at low temperatures was critical to
      assess a postsubmersion interval of 16-17 days.

PMID- 25613585
TI  - The novel histone deacetylase inhibitor, N-hydroxy-7-(2-naphthylthio)
      hepatonomide, exhibits potent antitumor activity due to cytochrome-c-release
      mediated apoptosis in renal cell carcinoma cells.
AB  - BACKGROUND: Epigenetic modifications play a critical role in the regulation of
      all DNA-based processes, such as transcription, repair, and replication.
      Inappropriate histone modifications can result in dysregulation of cell growth,
      leading to neoplastic transformation and cell death. Renal tumors have been shown
      to have a higher global methylation percentage and reduced histone acetylation.
      Preclinical models have revealed that histone gene modifiers and epigenetic
      alterations play important roles in renal cell carcinoma (RCC) tumorigenesis.
      Recently, a novel HDAC inhibitor, N-hydroxy-7-(2-naphthylthio) heptanomide
      (HNHA), has been introduced as an example of a new class of anti-cancer agents.
      The anti-cancer activity of HNHA and the underlying mechanisms of action remain
      to be clarified. METHODS: The MTS assay using a panel of RCC cells was used to
      evaluate the anti-proliferative effects of HNHA. The established HDAC inhibitors,
      SAHA and TSA, were used for comparison. Western blotting analysis was performed
      to investigate the acetylation of histone H3 and the expression of apoptotic
      markers in vitro and in vivo. Subcellular fractionation was performed to evaluate
      expression of Bax and cytochrome c in the cytosol and mitochondria, and also
      translocation of cytochrome c from the cytoplasm to the nucleus. A confocal
      microscopic evaluation was performed to confirm inhibition of cell proliferation,
      induction of apoptosis, and the nuclear translocation of cytochrome c in RCC
      cells. RESULTS: In this study, we investigated the apoptosis-inducing activity of
      HNHA in cultured kidney cancer cells. Apoptosis in the HNHA-treated group was
      induced significantly, with marked caspase activation and Bcl-2 suppression in
      RCC cells in vitro and in vivo. HNHA treatment caused cytochrome c release from
      mitochondria, which was mediated by increased Bax expression and caspase
      activation. HNHA also induced nuclear translocation of cytochrome c, suggesting
      that HNHA can induce caspase-independent nuclear apoptosis in RCC cells. An in
      vivo study showed that HNHA had greater anti-tumor and pro-apoptotic effects on
      RCC xenografts than the established HDAC inhibitors. CONCLUSIONS: HNHA has more
      potent anti-tumor activity than established HDAC inhibitors. Its activities are
      mediated by caspase-dependent and cytochrome-c-mediated apoptosis in RCC cells.
      These results suggest that HNHA may offer a new therapeutic approach to RCC.

PMID- 25613587
TI  - The antibacterial mechanism of berberine against Actinobacillus pleuropneumoniae.
AB  - This study demonstrated berberine to be a potential natural compound against
      Actinobacillus pleuropneumoniae. Liquid doubling dilution, transmission electron
      microscopy (TEM), SDS-PAGE and 4',6-diamidino-2-phenylindole (DAPI) staining were
      employed to elucidate the antibacterial activity and mechanism of berberine. The
      minimal inhibitory concentration of berberine was 0.3125 mg/mL, and time-kill
      curves showed concentration and time dependence. The TEM micrographs displayed
      damaged cell wall, concentrated cytoplasm, cytoplasmic content leakage and cell
      death. SDS-PAGE and DAPI assays revealed that berberine can restrain DNA and
      protein syntheses. Berberine inhibited the synthesis of proteins associated with
      the growth and cleavage of bacteria and then blocked the division and development
      of bacteria. The compound ultimately induced cytoplasm pyknosis and bacterial
      death.

PMID- 25613589
TI  - Menstrual cycle effects on psychological symptoms in women with PTSD.
AB  - The menstrual cycle has been implicated as a sex-specific biological process
      influencing psychological symptoms across a variety of disorders. Limited
      research exists regarding the role of the menstrual cycle in psychological
      symptoms among women with posttraumatic stress disorder (PTSD). The current study
      examined the severity of a broad range of psychological symptoms in both the
      early follicular (Days 2-6) and midluteal (6-10 days postlutenizing hormone
      surge) phases of the menstrual cycle in a sample of trauma-exposed women with and
      without PTSD (N = 49). In the sample overall, total psychological symptoms (d =
      0.63), as well as depression (d = 0.81) and phobic anxiety (d = 0.81) symptoms,
      specifically, were increased in the early follicular compared to midluteal phase.
      The impact of menstrual cycle phase on phobic anxiety was modified by a
      significant PTSD * Menstrual Phase interaction (d = 0.63). Women with PTSD
      reported more severe phobic anxiety during the early follicular versus midluteal
      phase, whereas phobic anxiety did not differ across the menstrual cycle in women
      without PTSD. Thus, the menstrual cycle appears to impact fear-related symptoms
      in women with PTSD. The clinical implications of the findings and future research
      directions are discussed. 

PMID- 25613588
TI  - Classifying adolescent attention-deficit/hyperactivity disorder (ADHD) based on
      functional and structural imaging.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common disabling psychiatric
      disorder associated with consistent deficits in error processing, inhibition and
      regionally decreased grey matter volumes. The diagnosis is based on clinical
      presentation, interviews and questionnaires, which are to some degree subjective
      and would benefit from verification through biomarkers. Here, pattern recognition
      of multiple discriminative functional and structural brain patterns was applied
      to classify adolescents with ADHD and controls. Functional activation features in
      a Flanker/NoGo task probing error processing and inhibition along with structural
      magnetic resonance imaging data served to predict group membership using support
      vector machines (SVMs). The SVM pattern recognition algorithm correctly
      classified 77.78% of the subjects with a sensitivity and specificity of 77.78%
      based on error processing. Predictive regions for controls were mainly detected
      in core areas for error processing and attention such as the medial and
      dorsolateral frontal areas reflecting deficient processing in ADHD (Hart et al.,
      in Hum Brain Mapp 35:3083-3094, 2014), and overlapped with decreased activations
      in patients in conventional group comparisons. Regions more predictive for ADHD
      patients were identified in the posterior cingulate, temporal and occipital
      cortex. Interestingly despite pronounced univariate group differences in
      inhibition-related activation and grey matter volumes the corresponding
      classifiers failed or only yielded a poor discrimination. The present study
      corroborates the potential of task-related brain activation for classification
      shown in previous studies. It remains to be clarified whether error processing,
      which performed best here, also contributes to the discrimination of useful
      dimensions and subtypes, different psychiatric disorders, and prediction of
      treatment success across studies and sites.

PMID- 25613590
TI  - Salty stories.

PMID- 25613591
TI  - Effects of the behavior of elderly type 2 diabetic patients and their relatives
      as caregivers on diabetes follow-up parameters in Bolu, Turkey.
AB  - AIM: In the present study, patients with type 2 diabetes mellitus and their
      relatives as caregivers during the treatment period, and the effects on treatment
      success were evaluated. METHODS: A cross-sectional study of type 2 diabetes
      mellitus patients aged 65 years and older and their relatives as caregivers was
      carried out. The questionnaire given to the participants consisted of three
      sections: the first section included questions regarding sociodemographic
      characteristics; the second section included questions on patient treatment,
      habits of drug use, lifestyle changes such as dietary habits; and the third
      section included anthropometric measurements and laboratory evaluations. The
      questionnaire given to the patients' relatives as caregivers consisted of
      questions regarding their sociodemographic characteristics and information
      regarding the patient. RESULTS: The present study consisted of 115 patients
      diagnosed with type 2 diabetes mellitus and their relatives as caregivers. The
      average duration of diabetes was 12.14 +/- 6.74 years. Body mass index was 30.2
      +/- 4.2 kg/m(2) , average hemoglobin A1c level was 7.09 +/- 0.64%, and 40.1% of
      the patients lived with their partners only. As the frequency of physical
      exercise increased, hemoglobin A1c levels decreased to <7.5% (P < 0.05).The
      patients whose caregivers were college-educated or equivalent had a significantly
      low body mass index (P < 0.05). Patients who lived with their partners showed a
      significant correlation with lower hemoglobin A1c levels (<7.5%; P = 0.002).
      CONCLUSION: In order to improve diabetic conditions in the elderly and to
      overcome obstacles to disease management, maximizing the cooperative efforts
      between the patients and their caregivers is necessary.

PMID- 25613592
TI  - Temporal Trends in Age at HIV Diagnosis in Cohorts in the United States, the
      Caribbean, and Central and South America.
AB  - In the United States (USA), the age of those newly diagnosed with HIV is
      changing, particularly among men who have sex with men (MSM). A retrospective
      analysis included HIV-infected adults from seven sites in the Caribbean, Central
      and South America network (CCASAnet) and the Vanderbilt Comprehensive Care Clinic
      (VCCC-Nashville, Tennessee, USA). We estimated the proportion of patients <25
      years at HIV diagnosis by calendar year among the general population and MSM.
      19,466 (CCASAnet) and 3,746 (VCCC) patients were included. The proportion <25
      years at diagnosis in VCCC increased over time for both the general population
      and MSM (p < 0.001). Only in the Chilean site for the general population and the
      Brazilian site for MSM were similar trends seen. Subjects <25 years of age at
      diagnosis were less likely to be immunocompromised at enrollment at both the VCCC
      and CCASAnet. Recent trends in the USA of greater numbers of newly diagnosed
      young patients were not consistently observed in Latin America and the Caribbean.
      Prevention efforts tailored to young adults should be increased. 

PMID- 25613593
TI  - Place of Residence Moderates the Relationship Between Emotional Closeness and
      Syringe Sharing Among Injection Drug Using Clients of Sex Workers in the US
      Mexico Border Region.
AB  - Injection drug-using men from the US and Mexico who purchase sex in Tijuana,
      Mexico are at risk for transmitting HIV to their contacts in both countries via
      syringe sharing. We used social network methods to understand whether place of
      residence (US vs. Mexico) moderated the effect of emotional closeness on syringe
      sharing. We interviewed 199 drug-using men who reported paying/trading for sex in
      Tijuana, Mexico using an epidemiological and social network survey and collected
      samples for HIV/STI testing. Seventy-two men reported using injection drugs with
      272 network contacts. Emotional closeness was strongly associated with syringe
      sharing in relationship where the partner lives in the US, while the relationship
      between emotional closeness and syringe sharing was considerably less strong in
      dyads where the partner lives in Mexico. Efforts to reduce HIV risk behaviors in
      emotionally close relationships are needed, and could benefit from tailoring to
      the environmental context of the relationship. 

PMID- 25613594
TI  - Comprehensive evaluation of caregiver-reported antiretroviral therapy adherence
      for HIV-infected children.
AB  - For HIV-infected children, adherence to antiretroviral therapy (ART) is often
      assessed by caregiver report but there are few data on their validity. We
      conducted prospective evaluations with 191 children ages 0-14 years and their
      caregivers over 6 months in western Kenya to identify questionnaire items that
      best predicted adherence to ART. Medication Event Monitoring Systems((r)) (MEMS,
      MWV/AARDEX Ltd., Switzerland) electronic dose monitors were used as external
      criterion for adherence. We employed a novel variable selection tool using the
      LASSO technique with logistic regression to identify items best correlated with
      dichotomized MEMS adherence (>=90 or <90 % doses taken). Nine of 48 adherence
      items were identified as the best predictors of adherence, including missed or
      late doses in the past 7 days, problems giving the child medicines, and caregiver
      level factors like not being present at medication taking. These items could be
      included in adherence assessment tools for pediatric patients. 

PMID- 25613595
TI  - Open Mind, Open Heart: An Anthropological Study of the Therapeutics of Meditation
      Practice in the US.
AB  - Based on ethnographic fieldwork and interviews collected with meditation teachers
      and students in the United States, this article will argue that active training
      in meditation-based practices occasions the opportunity for people with traumatic
      stress to develop a stronger mind-body connection through heightened somatic
      awareness and a focus on the present moment that they find to be therapeutic.
      Three important themes related to healing through meditation for trauma emerged
      from the data and centered around the ways our interlocutors attempted to realign
      their sense of self, mind and body, after a traumatic experience. The themes
      helped explain why US women perceive meditation as therapeutic for trauma, namely
      that the practice of meditation enables one to focus on the lived present rather
      than traumatic memories, to accept pain and "open" one's heart, and to make use
      of silence instead of speech as a healing modality. As meditation practices
      increasingly enter global popular culture, promoted for postulated health
      benefits, the driving question of this research--how meditation may perpetuate
      human resilience for women who have experienced trauma based on their own
      perspectives of meditation practices--is a critical addition to the literature.

PMID- 25613596
TI  - Navigating the cultural and professional legacies of alternative and mainstream
      medicine in nineteenth-century america: a review essay.

PMID- 25613598
TI  - Percutaneous treatment of common bile duct stones: results and complications in
      110 consecutive patients.
AB  - BACKGROUND/AIMS: Choledocholithiasis is a common complication of
      cholecystolithiasis, occurring in 15-20% of patients who have gallbladder stones.
      Endoscopic retrograde cholangio-pancreatography is the standard treatment. When
      this is not possible or not feasible, percutaneous transhepatic stone removal is
      an alternative treatment. In this retrospective study, we analyze 110 patients
      who were treated with percutaneous transhepatic removal of Common Bile Duct (CBD)
      stones. PATIENTS AND METHODS: Between March 1998 and September 2013 110 patients
      (61 men, 49 women; aged 14-96, mean age 69.7 years) with confirmed bile duct
      stones were included. PTC was done using ultrasound and fluoroscopy. Balloon
      dilatation of the papilla was done with 8-12 mm balloons. If stone size exceeded
      10 mm, mechanical lithotripsy was performed. Stones were then removed by
      percutaneous extraction or evacuation into the duodenum. RESULTS: In 104 patients
      (104/110; 94.5%) total stone clearance of the CBD was achieved. A total of 12
      complications occurred (10.9%), graded with the Clavien-Dindo scale as IVa, IVb,
      and V, respectively; hypoxia requiring resuscitation, sepsis and death due to
      ongoing cholangiosepsis (n = 1, 4, 1). Minor complications I, II, and IIIa
      included: small liver abscess, pleural empyema, transient hemobilia and mild
      fever (n = 1, 1, 2, 2). CONCLUSION: Percutaneous removal of CBD stones is an
      effective alternative treatment, when endoscopic treatment is contra-indicated,
      fails or is not feasible. It is effective, has a low complication rate and using
      deep sedation potentially requires only a very limited number of treatment
      sessions.

PMID- 25613597
TI  - Novel risk factors associated with current suicidal ideation and lifetime suicide
      attempts in individuals with spinal cord injury.
AB  - OBJECTIVE: To determine unique associations of suicidal ideation (SI) and
      lifetime suicide attempts (SAs) in individuals with spinal cord injury (SCI).
      DESIGN: Cross-sectional analysis. SETTING: Outpatient. PARTICIPANTS: Individuals
      with SCI (N=2533) who were 18 years or older with a history of traumatic SCI.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Any SI in the past 2 weeks (9-item
      Patient Health Questionnaire) and any lifetime SA. RESULTS: Three hundred twenty
      three individuals (13.3%) reported SI in the past 2 weeks and 179 (7.4%) reported
      lifetime SA. After controlling for other factors, both lifetime SA and current SI
      were associated with study site and current level of depression. In addition, SA
      was associated with less education, younger age at injury, having current or past
      treatment of depression, and having bipolar disorder or schizophrenia. SI was
      associated with more years since injury and lifetime SA. Several psychological
      factors were associated with current SI and lifetime SAs, including lower
      environmental reward and less positive affect. In addition, control of one's
      community activities and spiritual well-being were associated with current SI. In
      bivariate comparisons, severity of SCI was also associated with the 47% of the
      SAs that occurred after injury. CONCLUSIONS: Several unique associations of SI
      and lifetime SA in individuals with SCI were identified, including level of
      environmental reward and control, spiritual well-being, and severity of SCI.
      These factors bear further investigation as prospective risk factors for suicidal
      behavior after SCI.

PMID- 25613600
TI  - [Differential expression of bone morphogenetic protein and activin membrane-bound
      inhibitor in mouse adipose tissues and primary preadipocytes].
AB  - OBJECTIVE: To investigate the expression profiles of bone morphogenetic protein
      and activin membrane-bound inhibitor (BAMBI) during the development of mouse
      adipose tissue. METHODS: The total RNA was extracted for real-time PCR for
      amplification of BAMBI mRNA from the suprascapular brown adipose tissue (BAT) and
      subcutaneous (inguinal) and visceral (gonadal) white adipose tissue (sWAT and
      vWAT, respectively) of mice at various embryonic and postnatal stages, as well as
      from isolated primary preadipocytes during differentiation. RESULTS: In BAT,
      BAMBI mRNA levels exhibited a transient increase, peaking at day 0 (D0) and
      declined thereafter. sWAT and vWAT could be isolated from mice from postnatal D21
      onwards, in which BAMBI mRNA levels were the highest and decreased at 8 weeks and
      6 months. BAMBI mRNA levels were also significantly reduced in primary
      preadipocytes isolated from vWAT after induced differentiation. BAMBI mRNA
      expression level was higher in vWAT than in sWAT and BAT at the same
      developmental stages. CONCLUSION: BAMBI is differentially expressed in different
      adipose tissues and developmental stages, which supports the hypothesis that
      BAMBI plays a pivotal role in the development of adipose tissues.

PMID- 25613599
TI  - A number-form area in the blind.
AB  - Distinct preference for visual number symbols was recently discovered in the
      human right inferior temporal gyrus (rITG). It remains unclear how this
      preference emerges, what is the contribution of shape biases to its formation and
      whether visual processing underlies it. Here we use congenital blindness as a
      model for brain development without visual experience. During fMRI, we present
      blind subjects with shapes encoded using a novel visual-to-music sensory
      substitution device (The EyeMusic). Greater activation is observed in the rITG
      when subjects process symbols as numbers compared with control tasks on the same
      symbols. Using resting-state fMRI in the blind and sighted, we further show that
      the areas with preference for numerals and letters exhibit distinct patterns of
      functional connectivity with quantity and language-processing areas,
      respectively. Our findings suggest that specificity in the ventral 'visual'
      stream can emerge independently of sensory modality and visual experience, under
      the influence of distinct connectivity patterns. 

PMID- 25613601
TI  - [Role of RAGE in lipopolysaccharide-induced cytoskeletal changes in mouse
      pulmonary microvascular endothelial cells].
AB  - OBJECTIVE: To investigate lipopolysaccharide (LPS)-induced changes of
      cytoskeletal filamentous actin in primary isolated pulmonary microvascular
      endothelial cells (PMVECs) from wild-type and RAGE knock-out mouse. METHODS: The
      lungs of wild-type and RAGE knock-out mice were digested with collagenase type I
      to obtain endothelial cells purified by anti-CD31-coupled magnetic beads. The
      PMVEC identified by factor VIII labeling were stimulated with LPS at different
      concentrations and the changes of filamentous actin were observed by confocal
      microscopy. RESULTS: The cultured primary cells showed typical endothelial cell
      phenotype as examined with factor VIII labeling. LPS stimulation caused
      rearrangement of the cytoskeletal filament F-actin in wild-type mouse PMVECs with
      stress fiber formation, but such changes were not obvious in RAGE knock-out mouse
      PMVECs. CONCLUSION: Mouse PMVECs of a high purity can be obtained by immune
      magnetic beads. RAGE is involved in LPS-induced destruction of mouse PMVEC
      cytoskeletons.

PMID- 25613602
TI  - [Inhibitory effect of chloroquine on airway hyperresponsiveness in asthmatic
      mice].
AB  - OBJECTIVE: To investigate the effect of chloroquine on airway hyperresponsiveness
      in asthmatic mice and explore the possible mechanism. METHODS: Balb/c mouse
      models of asthma established using OVA received intraperitoneal injections of
      chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the
      final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and
      the total cell count and the counts of different cell populations in the
      bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The
      severity of lung inflammation was evaluated using HE staining, and the
      concentrations of IL-6 and PGF2alpha in the BALF were detected by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Chloroquine pretreatment significantly
      decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count
      (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2alpha levels in
      the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened
      inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the
      lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2alpha (P<0.001) in the
      BALF in the asthmatic mice. CONCLUSION: Chloroquine can inhibit AHR in asthmatic
      mice and produce better anti-inflammatory effect when combined with dexamethasone
      for treatment of neutrophilic asthma.

PMID- 25613603
TI  - [Role of PRKCD and ASK1 in U937 cell differentiation].
AB  - OBJECTIVE: To investigate the expression of ASK1 and PRKCD in the process of
      monocyte differentiation, and explore their role in functional changes of
      hypersplenism spleen macrophages (Mphi) in portal hypertension (PH). METHODS:
      U937 cells were stimulated to differentiate into monocyte/macrophage-like cells
      by cultivation in PMA and the mRNA expressions of ASK1 and PRKCD were detected by
      q-PCR and the changes of protein expression were identified by western blot
      analysis. The secretion of phagocytose related cytokines such as IL-10 and TNF
      alpha were tested by ELISA, and the function of the macrophage-like cells were
      studied by chicken red blood cell phagocytose test. RESULTS: The expressions of
      PRKCD and ASK1 mRNA were gradually decreased along with the cell differentiation,
      while the secretion of TNF-alpha was increased, IL-10 secretion reached a maximum
      at 24 h after PAM stimulation, and then gradually fell. The expression of ASK1
      and p-ASK1 were rapidly increased compared with the non-stimulated U937 cells,
      while the expression of PRKCD and p-PRKCD were sightly declined. The phagocytose
      test show that U937 cells induced with PMA were able to swallow the chicken red
      blood cell. CONCLUSION: Up-regulated protein expression of ASK1 and p-ASK1 and
      down-regulated protein expression of PRKCD and p-PRKCD in the process of PMA
      induced monocyte differentiation, are consist with the expression changes of
      splenic macrophage phagocytosis in hypersplenism, which leads to increased
      activity of Mphi.

PMID- 25613604
TI  - [Non-modified magnetic beads coupled with multiple real-time PCR for detection
      and quantification of mycotoxigenic fungi in paprika samples].
AB  - OBJECTIVE: To establish a method for detecting 3 common toxigenic molds
      (Aspergillus, Penicillium, and Fusarium) based on non-modified magnetic beads
      coupled with multiple real-time PCR (NMB-multiple qPCR). METHODS: The primers and
      genus-specific probes were designed based on the rDNA sequences to develop a
      multiple real-time PCR using non-modified magnetic bead to enrichment of fungal
      spores. The sensitivity, specificity and repeatability of this assay were
      evaluated. RESULTS: The detection limit of this assay for spiked samples was
      10(4) CFU/g, demonstrating a 10-fold greater detection sensitivity of this assay
      than that of real-time PCR. The NMB-multiple qPCR assay also showed good
      specificity and reproducibility and yielded comparable results with those by
      traditional colony counting method for spiked samples (P>0.05). CONCLUSION: NMB
      multiple qPCR assay we established allows rapid and sensitive detection of common
      mycotoxigenic fungi in paprika.

PMID- 25613605
TI  - [High glucose promotes vascular smooth muscle cell calcification by activating
      WNT signaling pathway].
AB  - OBJECTIVE: To investigate whether high glucose-induced vascular calcification is
      associated with WNT signaling pathway. METHODS: An in vitro model of human
      vascular smooth muscle cell (VSMC) calcification was induced by exposure of the
      cells to high glucose. The expressions of WNT signal molecules and bone-related
      proteins including Cbfa1, Osx, OCN and BMP2 were analyzed with qRT-PCR, and the
      cell calcification was assessed by alizarin red staining. The effect of Dkk1, a
      WNT signaling inhibitor, on high glucose-induced cell calcification was tested
      with alizarin red staining and calcium content analysis. RESULTS: High glucose
      activated WNT signaling pathway in human VSMCs by up-regulating the expressions
      of WNT signal molecules including Wnt3a, Wnt7a, Fzd4 and Wisp1 mRNA by 1.86,
      1.68, 2.1, and 2.3 folds, respectively, and by promoting the phosphorylation of
      beta-catenin (2.70?0.22, P<0.05), a key mediator of WNT signaling pathway.
      Inhibition of WNT signaling pathway by Dkk1 attenuated high glucose-induced VSMC
      calcification and down-regulated the expression of bone-related proteins Cbfa1,
      Osx, OCN, and BMP2 by (51?9)%, (58?11)%, (56?10)%, and (62?10)% (P<0.01).
      CONCLUSION: WNT signaling pathway is involved in high glucose-induced VSMC
      calcification.

PMID- 25613606
TI  - [Central pulse pressure but not brachial blood pressure is the predominant factor
      affecting aortic arterial stiffness].
AB  - OBJECTIVE: To investigate the differences in central hemodynamic indices between
      hypertensive and normotensive subjects and identify the blood pressure index that
      the most strongly correlate with arterial stiffness and vascular damage markers.
      METHODS: A cohort of 820 hypertensive patients and 820 normotensive individuals
      matched for age and gender were enrolled in this study. We measured carotid
      femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index
      (AIx) and central blood pressures using pulse wave analysis and applanation
      tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP)
      and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in
      these subjects. RESULTS: In both hypertensive and normotensive subjects, the
      central systolic blood pressure (SBP) and pulse pressure (PP) were significantly
      lower than brachial SBP and PP; this PP amplification was significantly lower in
      the normotensives (9.85?6.55 mmHg) than in the hypertensives (12.64?6.69 mmHg),
      but the amplification ratios were comparable between the two groups. Blood
      pressure and age were closely related with aortic arterial stiffness. Compared
      with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV
      and AIx, and showed significantly lowered PP amplification ratio with age.
      Central PP was more strongly related to arterial stiffness and vascular damage
      markers than the other pressure indices. Multivariate analyses revealed that
      carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not
      by the mean blood pressure or brachial PP. CONCLUSION: The central PP is a more
      direct indicator of central arterial stiffness and a better marker of vascular
      aging than other blood pressure variables. These findings support the use of
      central blood pressure as a treatment target in future trials.

PMID- 25613607
TI  - [Chemical modification endows heparin with low anticoagulant and high
      antineoplastic activities].
AB  - OBJECTIVE: To evaluate the anticoagulant and antineoplastic activities of
      chemically modified low-molecular-weight heparin (LMWH). METHODS: LMWH obtained
      by splitting unfractionated heparin (UFH) with sodium periodate oxidation and
      sodium borohydride reduction was subjected to acetylation catalyzed by DCC and
      DMAP to produce acetylated LMWH (ALMWH). The anticoagulant activity of ALMWH was
      determined in mice, and its antiproliferative and anti-invasion activities was
      assessed in human breast cancer cells MDA-MB-231 and MFC-7. RESULTS: The
      anticoagulant activity of LMWH was decreased significantly after acetylation. The
      concentrations of commercial LMWH* and ALMWH for doubling the coagulation time
      (CT) were 33.04 umol/L and 223.56 umol/L, respectively, and the IC(50) of ALMWH
      for doubling CT was 6 times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9,
      2.7 and 8.1 mmol/L both significantly inhibited the proliferation of MDA-MB-231
      and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger
      inhibitory effects. The IC(50) of LMWH and ALMWH for inhibiting cell
      proliferation was 3168.4 umol/L and 152.6 umol/L in MCF-7 cells, and 12299.6
      umol/L and 22.2 umol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all
      markedly suppressed the invasion of MDA-MB-231 cells with comparable effects.
      CONCLUSION: Chemical modification of structure can endow LMWH with a low
      anticoagulant and high antiproliferative activities.

PMID- 25613608
TI  - [Study of integrated state of HPV-16 infection in cervical cancer and
      precancerous tissues].
AB  - OBJECTIVE: To investigate the prevalence of physical state of HPV-16 DNA in
      cervical cancer and cervical precancerous carcinoma. METHODS: Multiplex PCR was
      adopted to detect the physical state of HPV in samples from 252 patients with
      cervical carcinoma, including 48 samples of cervical cancer, 204 cervical
      intraepithelial neoplasia (CIN ) (125 CIN I, 46 CIN II and 33 CIN III) and 20
      normal samples from the subjects with hysteromyoma undergoing hysterectomy,
      respectively. RESULTS: Among 48 patients with cervical cancer, 31 (65.6%) were
      infected with HPV-16. Eighteen among 31 (58.1%) HPV-16 infected patients with
      cervical cancer were found to have integrated infection of HPV-16. The positive
      rates of HPV-16 infection in the patients with CIN I, CIN II and CIN III were
      19.2%, 34.8% and 42.4%, and the integrated infection rates of HPV-16 were 16.7%,
      18.8% and 35.7%, respectively. Compared with patients with different grades of
      CIN, the integrated rate of HPV-16 infection in those with cervical cancer was
      significantly elevated. CONCLUSION: Among the patients with HPV-16 infection, the
      integrated state of HPV-16 is positively correlated with the severity of cervical
      lesions. Combined HPV typing test and detection of integrated viral state
      contribute to predicting the prognosis of patients with cervical precancerous
      lesions and increasing the accuracy of screening cervical cancer on the basis of
      HPV DNA detection.

PMID- 25613609
TI  - [Changes of C3a in induced sputum in patients with asthma].
AB  - OBJECTIVE: To investigate the clinical significance of anaphylatoxin C3a in
      induced sputum in patients with asthma. METHODS: The patients with acute
      exacerbation of asthma treated at our department between September, 2006 and
      February, 2007 were included in the study. The demographic data, medical history,
      levels of lung function and C3a levels in induced sputum were assessed. RESULTS:
      A total of 33 patients were included in the study. The level of C3a in induced
      sputum was significantly higher in patients with acute exacerbation of asthma
      (2.24 ng/ml, range 1.68-5.58 ng/ml) than that in patients with asthma remission
      (0.7 ng/ml, range 0.24-2.31 ng/ml, P<0.05). Sputum C3a levels in the remission
      patients were significantly higher than those in the healthy controls (0.12
      ng/ml, range 0.07-0.39 ng/ml, P<0.05). The levels of C3a in patients with severe
      exacerbation (4.69 ng/ml, range 2.69-6.59 ng/ml) were significantly higher than
      those in patients with mild exacerbation (0.25 ng/ml, range 0.09-0.40 ng/ml) and
      moderate exacerbation (2.21 ng/ml, range 1.16-3.41 ng/ml) (P<0.01), and were
      significantly higher in patients with moderate exacerbation than in those in mild
      exacerbation (P<0.01). The level of C3a in induced sputum was positively
      correlated with the number of total cell count (r=0.718, P<0.05), eosinophils
      (r=0.495, P<0.05) and macrophages (r=0.600, P<0.05) in patients with acute
      exacerbation of asthma. CONCLUSION: Induced sputum C3a level can serve as an
      important clinical biomarker for clinical asthma management.

PMID- 25613610
TI  - [Establishment of a NOD/SCID mouse model with human immune reconstitution bearing
      human triple-negative breast cancer].
AB  - OBJECTIVE: To establish a NOD/SCID mouse model with human immune reconstitution
      and observe its immune response to human triple-negative breast cancer xenograft.
      METHODS: Twenty-four NOD/SCID mice without immune leakage were subjected to
      cyclophosphamide (CTX) treatment 3 days prior to immune reconstitution with human
      peripheral blood mononuclear cell (PBMC) injection and subcutaneous
      transplantation of human triple-negative breast cancer MDA-MB-231 cells, CTX
      treatment and PBMC injection without tumor cell transplantation, MDA-MB-231 cell
      transplantation only, or no treatments. The tumor growth and immune responses of
      the mice were observed at regular intervals. RESULTS: Compared with the tumor
      bearing mice, the tumor-bearing mice with immune reconstitution showed prolonged
      incubation period of tumor formation, slower tumor growth rate and increased
      survival rate. Human IgG and CD3(+) T cells were detected in the peripheral blood
      of the mice 1 week after human PBMC injection. The percentage of CD3(+) T cells
      in the spleen cells was 55.3% at 9 weeks in tumor-bearing mice with immune
      reconstitution and 52.7% in tumor-bearing mice without immune reconstitution. The
      spleen index of the tumor-bearing mice with immune reconstitution was much higher
      than that in mice with only immune reconstitution and the control mice (9.64 vs
      3.82?0.31 and 1.51?0.14 mg/g). CONCLUSION: A stable NOD/SCID mouse model with
      immune reconstitution has been established successfully, which shows immune
      responses to triple-negative breast cancer xenografts and allows studies of
      immunological therapy study of triple-negative breast cancer.

PMID- 25613611
TI  - [Sodium valproate enhances doxorubicin cytotoxicity in breast cancer cells in
      vitro].
AB  - OBJECTIVE: To investigate the effect of sodium valproate, a histone deacetylase
      inhibitor, on the cytotoxicity of doxorubicin in breast cancer cells. METHODS:
      Western blotting was used to assess Cx43 protein expression in breast cancer
      Hs578T cells exposed to doxorubicin and sodium valproate. MTT assay was used to
      determine the cytotoxicity of doxorubicin; annexin V/PI double staining and
      Hochest 33258 fluorescence staining were employed to detect doxorubicin-induced
      early and late apoptosis, respectively. RESULTS: Western blotting showed that
      sodium valproate significantly increased Cx43 protein expression in Hs578T cells
      (P/0.01). The cells exposed to both sodium valproate and doxorubicin showed
      significantly lowered cell viability compared with the cells exposed to
      doxorubicin alone (P/0.01). Exposure to both sodium valproate and doxorubicin
      resulted in significantly increased early and late cell apoptosis rate compared
      with doxorubicin treatment alone (P/0.01). CONCLUSION: sodium valproate can
      significantly enhance the cytotoxicity of doxorubicin and increase doxorubicin
      induced apoptosis in breast cancer cells in vitro possibly by enhancing the gap
      junction function.

PMID- 25613612
TI  - [Establishment of a rotary aerobic culture system for in vitro culture of mouse
      testis].
AB  - OBJECTIVE: To establish an in vitro model of cultured mouse testis using rotary
      aerobic culture. METHODS: Rotary aerobic incubation with optimized culture
      conditions was used for in vitro culture of mouse testis, and the morphology of
      the cultured testicular tissues was compared with that cultured in Transwell
      chambers. The changes in the testicular tissue structure were examined using HE
      staining, and the cell proliferation was assessed with BrdU staining.
      Testosterone concentrations in the culture medium were tested with
      radioimmunoassay and the expression of the functionally related proteins in the
      testis was detected using immunohistochemistry. RESULTS: The testicular tissue
      cultured by optimized rotary aerobic culture presented with more intact
      histological structure with the size of the testis ranged from 0.3 to 0.8 mm(3).
      In the two culture systems, the prolifeation index of the spermatogonia increased
      and that of Sertoli cells decreased with time, and such changes in spermatogonia
      and Sertoli cell proliferation indices became statistically significant at 3 days
      (P<0.05) and 5 days (P<0.05) of culture, respectively, as compared with those at
      1 day. The concentration of testoerone in the culture media decreased
      significantly with incubation time (P<0.05). At 3 days of culture, the protein
      expression of 3beta-hydroxysteroid dehydrogenase, cytochrome P450 17alpha
      hydroxylase and cholesterol side-chain cleavage enzyme was detected in Leydig
      cell cytoplasm and vimentin expression in Sertoli cell cytoplasm. CONCLUSION: An
      in vitro model of cultured mouse testis has been successfully established using
      rotary aerobic incubation.

PMID- 25613613
TI  - [Tetramethoxystilbene, a selective CYP1B1 inhibitor, suppresses adipogenesis of
      C3H10T1/2 pluripotent stem cells].
AB  - OBJECTIVE: To investigate the inhibitory effects of tetramethoxystilbene, a
      selective CYP1B1 inhibitor, on adipogenic differentiation of C3H10T1/2 multi
      potent mesenchymal cells. METHODS: In vitro cultured C3H10T1/2 cells at full
      confluence were induced by adipogenic agents (10 ug/ml insulin, 2 umol/L
      dexamethasone and 0.5 mmol/L 3-isobutyl-1-methylxanthine) and exposed
      simultaneously to TMS at the final concentrations of 1.0, 2.0 or 4.0 ug/ml. Oil
      Red-O staining was used to observe the cell differentiation. The expression of
      peroxisome proliferator-activated receptor gamma (PPARgamma) and its target genes
      cluster of differentiation 36 (CD36) and fatty acid binding protein 4 (FABP4)
      were quantified by real-time RT-PCR and Western blotting. RESULTS: Oil Red-O
      staining and TG contents revealed that TMS suppressed induced differentiation of
      C3H10T1/2 cells. TMS exposure of the cells dose-dependently decreased both mRNA
      and protein expressions of PPARgamma, a key nuclear transcription factor during
      adipogenesis, and also lowered the mRNA expressions of PPARgamma target genes
      CD36 and FABP4. CONCLUSION: TMS can suppress adipogenic differentiation of
      C3H10T1/2 cells by inhibiting PPARgamma

PMID- 25613614
TI  - [Placental Foxp3 expression in patients with preeclampsia and correlation of
      Foxp3 gene locus 924 (rs2232365) polymorphism with preeclampsia].
AB  - OBJECTIVE: To detect changes of Foxp3 expression in the decidua in patients with
      preeclampsia and investigate the correlation of Foxp3-924 (rs2232365)
      polymorphisms with preeclampsia. METHODS: From October 2011 to December 2012, 252
      normal pregnant women and 156 preeclampsia patients of Han nationality from the
      same geographic region were tested for Foxp3-924 genotypes by polymerase chain
      reaction with sequence-specific primer (PCR-SSP). Sixty-eight of the patients
      with preeclampsia (33 with mild and 35 with severe preeclampsia) and 30 of the
      normal pregnant women were also examined for Foxp3 expression in the decidua
      using immunohistochemical method. RESULTS: Foxp3 positive expression rates in the
      decidua was 51.52% in mild preeclampsia and 28.57% in severe preeclampsia cases,
      significantly lower than that in the control group (86.67%, P<0.05). In
      preeclampsia patients, the frequencies of Foxp3-924G/G, G/A, and A/A genotypes
      were 0.1346, 0.4615 and 0.4038, respectively, and the frequencies of Foxp3-924A
      and Foxp3-924 G were 0.6346 and 0.3654, respectively. The genotype frequencies of
      Foxp3-924G/G, G/A and A/A in the control group were 0.1508, 0.4087 and 0.4405,
      respectively, and the frequencies of Foxp3-924 A and Foxp3-924 G were 0.6448 and
      0.3552, respectively. No significant differences were found in the gene
      frequencies of Foxp3-924G/A between preeclampsia patients and the control group
      (P>0.05). CONCLUSION: The expression level of Foxp3 in the placental tissue of
      preeclampsia patients is significantly lower than that in normal pregnant women,
      suggesting that lowered Foxp3 expression decreases the immunosuppressive function
      and causes imbalance of immune tolerance between maternal-fetal to induce
      preeclampsia. Foxp3-924 polymorphisms is not significantly correlated with the
      occurrence of preeclampsia.

PMID- 25613615
TI  - [Effectiveness and safety of azithromycin in the treatment of bronchial asthma: a
      meta-analysis].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of azithromycin in treatment
      of bronchial asthma. METHODS: Reports of randomized controlled trials (RCTs)
      describing azithromycin for treatment of asthma published before December 2013
      were searched in CNKI, WANFANG, PubMed and Medline databases. The data of the
      included RCTs were extracted and the data quality was evaluated by two assessors
      independently. Meta-analyses were performed with Revman 5.1 software. RESULTS:
      Eight RCTs were identified. Meta-analysis of the data showed that compared with
      the control group, azithromycin treatment significantly improved the patients'
      PEF (WMD=0.15, 95%CI=0.06-0.24, P=0.001), scores of asthma control test (ACT)
      (WMD=1.59, 95%CI=0.95-2.23, P<0.00001), and FEV1% (WMD=1.44, 95%CI=0.40-2.49,
      P=0.007), but the improvement of FEV1% was observed only in Chinese patients
      (WMD=1.48, 95%CI=0.40-2.57, P=0.007). The scores of asthma control questionnaire
      (WMD=0.07, 95%CI=-0.11-0.25, P=0.45) or asthma quality of life questionnaire
      (WMD=-0.06, 95%CI=-0.42-0.31, P=0.77) were not affected by azithromycin. No
      severe adverse events were reported in these included studies. CONCLUSION:
      Azithromycin for asthma treatment can improve PEF, ACT and FEV1% (in Chinese
      patients only) but shows no significant effect on the quality of life of the
      patients. Azithromycin is well tolerated and may therefore be beneficial as
      adjuvant therapy for asthma.

PMID- 25613616
TI  - [Cisplatin inhibits proliferation of cervical carcinoma cell line by up
      regulating Stat1 expression].
AB  - OBJECTIVE: To investigate the role of Stat1 gene in the proliferation and
      chemotherapeutic sensitivity of cervical cancer HeLa cells. METHODS: The protein
      expression of Stat1 in the Hela cells exposed to gradient concentrations of
      cisplatin (DDP) was detected by Western blotting with or without small
      interfering RNA (siRNA)-mediated Stat1 gene silencing. The effect of Sata1
      silencing on the sensitivity to DDP and cell proliferation of the cells was
      tested using MTT assay and BrdU assay, and the expression of c-Myc was detected
      by Western blotting in the cells treated with siRNA and DDP. RESULTS: The
      expression of Stat1 in Hela cells exposed to DDP increased with the DDP
      concentrations, reaching 1.5 folds of the baseline at a DDP concentration of 5
      mg/L and 2 folds at 10 mg/L. Stat1-siRNA effectively reduced Stat1 expression in
      Hela cells, promoted the cell proliferation, and enhanced the expression of c
      Myc; DDP inhibited the cell growth and down-regulated c-Myc expression. Stat1
      siRNA rescued DDP-induced inhibition of cell growth and c-Myc down-regulation.
      CONCLUSION: The expression of Stat1 is associated with DDP sensitivity in
      cervical cancer cells, and Stat1 silencing can increase the sensitivity to DDP
      and c-Myc expression of the cells.

PMID- 25613617
TI  - [Functional analysis of cancer-derived immunoglobulin G whole molecule
      interacting proteins identified by LC-MS/MS].
AB  - OBJECTIVE: To identify cancer-derived immunoglobulin G (IgG) whole molecule
      interacting proteins to provide important clues for studying IgG biological
      functions. METHOS: HeLa cell lysate was immunoprecipitated with rabbit antihuman
      IgG whole molecule antibody and normal rabbit IgG. The immunocomplex underwent
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and was
      detected with silver staining. Three prominently enhanced bands were subjected to
      protein identification with liquid chromatography-tandem mass spectrometry (LC
      MS/MS), and the MS data were analyzed with Swiss-Prot database. Cancer-derived
      IgG whole molecule-interacting proteins were screened and functionally annotated.
      RESULTS AND CONCLUSION: We identified 6 potential cancer-derived IgG whole
      molecule-interacting proteins with co-immunoprecipitation combined with LC-MS/MS,
      which provides valuable clues for studying the function of cancer-derived IgG.

PMID- 25613618
TI  - [Mitochondrial estrogen receptor beta inhibits non-small cell lung cancer cell
      apoptosis via interaction with Bad].
AB  - OBJECTIVE: To explore the molecular mechanisms by which mitochondrial estrogen
      receptor beta (ERbeta) suppresses non-small cell lung cancer cell apoptosis
      induced by apoptotic stimulations. METHODS: The mitochondrial localization of
      ERbeta in non-small cell lung cancer cell lines A549 and 201T was determined
      using immunofluorescence and Western blotting. The changes of apoptosis of the
      cells with mitochondrial ERbeta overexpression or knockdown in response to
      cisplatin and STS treatments were assessed, and mitochondrial ERbeta interaction
      with the pro-apoptotic protein Bad was detected using co-immunoprecipitation and
      Western blotting. RESULTS: ERbeta was localized in the mitochondria in A549 and
      201T cells. ERbeta overexpression significantly reduced while ERbeta knockdown
      increased Bax activation and cell apoptosis induced by cisplatin and STS.
      Mitochondrial ERbeta interaction with pro-apoptotic protein Bad may suppress Bax
      activation and its translocation to the mitochondria. CONCLUSION: Mitochondrial
      ERbeta can suppress apoptosis of non-small cell lung cancer cells induced by
      cisplatin or STS through interaction with Bad, suggesting the value of
      mitochondrial ERbeta as a new therapeutic target for treatment of non-small cell
      lung cancer.

PMID- 25613619
TI  - [Expression of enhancer of zeste homolog 2 in esophageal squamous cell carcinoma
      and its prognostic value in postoperative patients].
AB  - OBJECTIVE: To investigate the expression of enhancer of zeste homolog 2 (EZH2) in
      esophageal squamous cell carcinoma and its association with the prognosis of
      postoperative patients. METHODS: Surgical specimens were obtained from 102
      patients with esophageal squamous cell carcinoma undergoing radical resection in
      our hospital from 1996 to 2006. Immunochemistry was employed to examine EZH2
      protein expressions in the specimens, including 102 carcinoma tissue specimens,
      30 adjacent tissue specimens and 30 normal esophageal tissue specimens. The
      expression levels of EZH2 were analyzed in relation to the clinicopathological
      parameters of the patients including gender, age, tumor differentiation, TNM, and
      lymph node metastasis. The postoperative patients were followed up to analyze the
      association of EZH2 expression with the clinical outcomes. RESULTS: The
      esophageal squamous cell carcinoma tissue showed a higher EZH2 expression than
      the adjacent and normal esophageal tissues. EZH2 expression was higher in poorly
      differentiated carcinoma than in well differentiated tissue, and also higher in
      cases with lymph node metastasis than those without; the expression was higher in
      TNM stage II/III patients than in stage I patients but lower than in stage IV
      patients. The patients with low EZH2 expression was found to have a longer
      survival time than those with high EZH2 expression (P<0.05). CONCLUSION: EZH2
      plays an important role in the differentiation and metastasis of esophageal
      squamous cell carcinoma, and a high EZH2 expression is associated with a poor
      outcome in the the postoperative patients.

PMID- 25613620
TI  - [Establishment of a cell model of insulin-resistant 3T3-L1 adipocytes].
AB  - OBJECTIVE: To investigate the optimal conditions for establishing insulin
      resistant 3T3-L1 adipocytes. METHOS: Dexamethason (DEX), 3-isobutyl
      methylxanthine (IBMX) and different concentrations of insulin (10(-8), 10(-7),
      and 10(-6) mol.L(-1)) were used to induce 3T3-L1 preadipocytes into mature
      adipocytes identified by oil red O staining. We established insulin- resistant
      3T3-L1 adipocytes cell model (IR-3T3-L1) by exposing the cells to 1umol.L(-1)
      DEX, and the changes of glucose concen- tration in the cell culture were
      determined by glucose oxidase-peroxidase (GOD-POD) assay. RESULTS: Treatment of
      3T3-L1 cells with DEX, IBMX and 10(-6) mol.L(-1)) insulin for 9 days resulted in
      the differentiation of >90% of the cells into mature adipocytes. IR-3T3-L1 cells
      cultured for 96 h in the culture media containing 1 umol.L(-1) DEX showed
      significantly increased glucose consumption (P=0.0003) as compared with the
      control group at 36 h (P<0.001). CONCLUSION: 3T3-L1 cells can be induced into
      mature adipocytes by exposure to 1 umol.L(-1) DEX, 0.5 mmol.L(-1) IBMX and 10(-6)
      mol.L(-1)) insulin. A 96 h exposure to 1 umol.L(-1) DEX can induce 3T3-L1
      adipocytes to acquire insulin resistance that can be maintained for 36 h.

PMID- 25613621
TI  - [Rutin protects against trimethyltin-induced learning and memory impairment in
      BALB/c mice by antagonizing down-regulated synaptophysin expression].
AB  - OBJECTIVE: To explore the protective effects of rutin against learning and memory
      impairment induced by trimethyltin (TMT) and investigate the possible mechanism.
      METHODS: Forty 6- to 9-week-old male BALB/c mice were randomized equally into
      saline group (control), TMT group, TMT+rutin group, and rutin group. Mouse models
      of learning and memory impairment were establish by acute TMT (2.25 mg/kg)
      exposure. In TMT+rutin and rutin treatment groups, the mice received
      intraperitioneal injection of rutin (10 mg/kg) for 1 week before TMT exposure.
      Twenty-four hours after TMT exposure, Morris water maze test was employed to test
      the escape latency of the mice, and the synaptophysin expression in the
      hippocampus and cortex were analyzed by Western blotting. RESULTS: Compared that
      in TMT group, the escape latency of the mice in water maze test was significantly
      shorter in the other 3 groups (P<0.05); the escape latency in TMT +rutin group
      was similar with that in the control and rutin groups (P>0.05). Western blotting
      showed significantly decreased synaptophysin expression in the hippocampus and
      cortex in TMT group (P<0.05); synaptophysin expression in TMT +rutin group
      increased significantly compared with that in TMT group (P<0.05) but showed no
      statistical significance from that in rutin and control groups (P>0.05).
      CONCLUSION: Rutin pretreatment offers protective effect against TMT-induced
      learning and memory impairment in mice possibly by antagonizing decreased
      synaptophysin in the hippocampus and cortex.

PMID- 25613622
TI  - [ERKl/2 signaling pathway mediates heme oxygenase-1 up-regulation by minocycline
      in PC12 cells exposed to oxygen glucose deprivation].
AB  - OBJECTIVE: To investigate the effects of minocycline in promoting the survival of
      pheochromocytoma (PCI2) cells exposed to oxygen glucose deprivation (OGD) and
      explore the underlying mechanisms. METHODS: An in vitro cell model of cerebral
      ischemia was established by OGD for 6 h in PCI2 cells with pretreatment with
      minocycline or an ERK1/2 inhibitor. At 24 h after OGD injury, the cells were
      evaluated for cell viability by MTT assay and expressions of heme oxygenase-I (HO
      I) and phospholylated extracellular signal-regulated protein kinase 1/2 (ERK1/2)
      by Western blotting. RESULTS: The cell viability decreased dramatically following
      OGD. Pretreatment with minocycline (O.I-IO JJ.mol/L) induced a significant
      increase in the cell viability after OGD and caused up-regulation of HO-I protein
      and enhanced ERK1/2 phospholylation, and the effects were especially obvious with
      1 JJ.mol/L minocycline and were abolished by inhibition of ERK1/2 activity with
      UOI26 (IO JJ.mol/L). CONCLUSION: Minocycline can protect PCI2 cells against OGD
      induced toxicity by up-regulating HO-I protein expression through ERKl/2
      signaling pathways.

PMID- 25613623
TI  - [Diagnostic value of (18)F-FDG PET/CT for solitary nodular-type bronchoalveolar
      carcinoma].
AB  - OBJECTIVE: To assess the value of (18)F-FDG PET/CT in the diagnosis of solitary
      nodular-type bronchoalveolar carcinoma (BAC). METHODS: The clinical and
      radiographic data were analyzed retrospectively in 30 patients with
      pathologically confirmed solitary nodular-type BAC who underwent (18)F-FDG PET/CT
      examinations between August, 2005 and December, 2006. The morphological and
      radioactive findings of the lesions were reviewed, and the maximum standard
      uptake values (SUVmax) were measured. The diagnostic accuracy of PET, PET/CT, and
      HRCT were analyzed. RESULTS: The (18)F-FDG SUV was markedly lower in BAC than in
      other well differentiated adenocarcinoma. In 19 of the BAC cases, PET showed a
      SUVmax of no less than 2.5, demonstrating positive changes. Of the total of 30
      cases, 5 had ground glass opacity (GGO) changes, 3 exhibited mixed nodules with
      GGO changes around the lesions, and 22 cases presented with solid nodules. HRCT
      showed that BAC located often in the superior lobes of the bilateral lungs,
      mostly below the pleura in the surrounding lung field; the lesions were patchy or
      nodular with irregular shapes, showing lobulation in 22 cases, spiculation in 15
      cases, pleural indentation in 21 cases, and vacuolar changes in 4 cases. The
      diagnostic accuracy of PET, PET/CT and HRCT for solitary nodular-type BAC was
      36.67%, 93.33%, and 93.33%, respectively. CONCLUSION: The SUVmax of BAC provides
      only limited value for defining the nature of the lesions, but can serve as a
      general reference for assessing the disease activity. PET/CT, which allows both
      functional and imaging assessment, can be a valuable modality to reduce the
      misdiagnosis rate of BAC.

PMID- 25613624
TI  - [Diagnosis and treatment of multiple intracranial aneurysms].
AB  - OBJECTIVE: To explore the diagnosis and treatment strategy of multiple
      intracranial aneurysms (MIA). METHODS: We retrospectively analyzed 96 patients
      with MIA (234 aneurysms). The rupture site was determined on the basis of
      computed tomographic and angiographic findings, and the supposed ruptured
      aneurysm was treated with coiling OR clipping. All the patients' records were
      reviewed including all computed tomographic scans and angiograms. RESULTS: Twelve
      patients received conservative treatment, 56 patients were treated by
      endovascular embolization, and 28 patients received clipping; 44 patients
      received one-stage treatment, and 4 patients needed a second therapy. In 36
      patients, only the ruptured aneurysm was eliminated. The clinical outcomes of
      these 84 patients evaluated by Glasgow Outcome Scale grades were: absence of
      deficits in 62 patients, minor deficits in 12 patients, major deficit in 8
      patients; death occurred in 2 cases. Thirty patients were available for a 6-month
      follow-up with DSA, which revealed stable occlusion of the aneurysms in 29
      patients and the need of a retreatment due to recanalization in only one patient.
      CONCLUSION: Correct localization of the rupture aneurysm based on a comprehensive
      diagnosis is key to MIA treatment. All the aneurysms should be treated in one
      session whenever possible to protect the patient from rebleeding.

PMID- 25613625
TI  - [Inhibition of microRNA-23a increases cisplatin sensitivity of ovarian cancer
      cells: the possible molecular mechanisms].
AB  - OBJECTIVE: To investigate the changes in cisplatin sensitivity of resistant
      ovarian cancer A2780 cells after inhibition of miR-23a expression and explore the
      molecular mechanisms. METHODS: The drug-resistant ovarian cancer A2780 cells were
      exposed to cisplatin alone or in combination with antagomir-23a. The cell
      inhibition rates after the treatments were detected using MTT assay, cell cycle
      changes assessed with flow cytometry; and apoptotic cells observed using
      Hoechst33258 staining. The changes in glycoprotein P-gp expression in the cells
      were detected using Western blotting. RESULTS: Inhibition of miR-23 a combined
      with cisplatin treatment significantly increased the cell inhibition rate
      (P<0.01) and lowered the IC(50) so of cisplatin by 83.76% from 110.18 MUmol/L in
      the control group to 17.89 MUmol/L (P<0.01). The combined treatments also caused
      cell cycle arrestin G0/G1 phase, increased the cell apoptosis rate (P<0.01) and
      the number of cells stained with Hoechst33258; the cellular expression of P-gp
      protein was significantly reduced as the cisplatin doses increased (P<0.01).
      CONCLUSION: Inhibition of miR-23a expression increases the sensitivity of A2780
      cells to cisplatin possibly by inhibiting the negative regulation by miR-23a
      target genes that causes inhibition of P-gp protein expression.

PMID- 25613626
TI  - [E-cadherin expression and CDH1 promoter methylation in sporadic and hereditary
      gastric cancer].
AB  - OBJECTIVE: To evaluate the role of E-cadherin (E-cad) and CDH1 gene encoding E
      cad in the occurrence of sporadic or hereditary gastric cancer. METHODS: Nineteen
      normal gastric mucosal issue specimens, 19 specimens of hereditary gastric cancer
      (diagnosed according to ICG-HGC criteria), and 19 specimens of sporadic gastric
      cancer examined for E-cad expression and CDH1 promoter methylation using
      immunohistochemistry and methylation-specific PCR (MSP). RESULTS: The protein
      expression of E-cad were significantly reduced in both of the cancer tissues
      (P<0.001) compared with that in the normal gastric mucosal tissues, and showed no
      significant difference between the two cancers (P=0.84). CDH1 promoter
      hypermethylation was found in 10 out of the 19 hereditary gastric cancer tissues,
      a rate significantly higher than that in sporadic gastric cancer tissues (3/19,
      P<0.01). CONCLUSION: CDH1 promoter hypermethylation is probably an important
      factor contributing to reduced E-cad expression in sporadic gastric cancer but
      not in hereditary gastric cancer.

PMID- 25613627
TI  - [Expression of SOX2 in cervical intraepithelial neoplasia and cervical cancer and
      its clinical significance].
AB  - OBJECTIVE: To investigate the expression of SOX2 in cervical intraepithelial
      neoplasia (CIN) and cervical cancer and explore its association with the clinical
      features. METHODS: SOX2 expressions were examined using immunohistochemical
      method in 10 normal cervical tissue specimens, 36 cervical intraepithelial
      neoplasia specimens (including 10 cases of grade I, 12 of grade II, and 14 grade
      III) and 40 cervical cancer specimens (including 21 cases of stage I and 19 of
      stage II). The correlation between the immunohistochemical results and the
      clinical features of the patients was analyzed. RESULTS: SOX2 expression was
      negative in normal cervical tissues, and was positive in 41.6% of CIN specimens
      (10.0% in CIN I, 41.7% in CIN II, and 64.3% in CIN III) in 82.5% of cervical
      cancer specimens (78.2% in stage I and 88.2% in stage II). The patients with
      cervical cancer had a significantly higher positivity rate of SOX2 than normal
      control group (P<0.05). The positivity rate of SOX2 increased with the evolution
      of cervical disease. SOX2 protein expression was significantly correlated with
      the histological grade and lymph node metastasis (P<0.05), but not with the age
      or clinical stage of the patients (P<0.05). CONCLUSION: SOX2 expression may serve
      as a useful indicator for evaluating metastasis and malignancy of cervical
      cancer.

PMID- 25613628
TI  - [Hybrid operation for acute left leg deep venous thrombosis secondary to left
      iliac vein compression syndrome: analysis of 36 cases].
AB  - OBJECTIVE: To evaluate the surgical techniques for acute left deep venous
      thrombosis (LDVT) secondary to left iliac vein compression syndrome (IVCS).
      METHODS: Thirty-six patients with acute LDVT secondary to IVCS received inferior
      vena cava filter placement, and in 2 of the cases, stent implantation was
      canceled for acute episode of obsolete DVT. The remaining 34 patients underwent
      left femoral venotomy for iliofemoral thrombectomy with Fogarty catheter and
      distal femoral vein thrombus removal by sequential compression of the legs,
      followed by implantation of stent-graft (2 cases) or bare-metal stents (32 cases)
      in the left common iliac veins. With routine anticoagulation and thrombolytic
      treatments, the patients were regularly examined for postoperative blood flow in
      the affected limb. RESULTS: In 2 of the cases undergoing bare-metal stent
      implantation, the residue thrombi were squeezed into the stent by balloon, which
      was managed subsequently with local thrombolysis. One patient with bare-metal
      stent implantation received a secondary stenting for posterior stent
      displacement. Three patients had self-limited bleeding due to decreased serum
      FBG. Significant improvements were achieved at 3, 6, 30 and 180 days
      postoperatively in the circumferences of the affected limb (P<0.05) and in the
      levels of D-dimer (P=0.011), and FBG level showed no significant variations
      (F=1.163, P=0.345). The total rate of excellent outcomes was 83.3% (26/34) with a
      total effective rate of 91.2% (31/34) in these cases. CONCLUSIONS: Thrombectomy
      to revascularize the inflow tract and stent implantation to enlarge stenosed
      iliac veins are key issues in treatment of acute LDVT secondary to IVCS.

PMID- 25613629
TI  - [Expressions of microtubule-associated protein 2 and nestin in the development of
      human embryo and fetal tongue muscles].
AB  - OBJECTIVE: To explore the role of microtubule-associated protein 2 (MAP-2) and
      nestin in the development of tongue muscles of human embryos and fetuses.
      METHODS: PV immunohistochemistry was used to detect the expressions of MAP-2 and
      nestin proteins in the tongue tissues of human embryos and fetuses at the second,
      third and fourth months of gestation. RESULTS: MAP-2 and nestin positivity was
      detected in the tongue muscles of human embryos at 2 to 4 months of gestation. In
      the embryos at the second month of gestation, no obvious MAP-2 positive cells
      were found in the tongue muscles; at 3 and 4 months, the number of MAP-2-positive
      cells in the tongue muscles was 24.14?8.28 and 15.86?3.89, with the expression
      intensity of 109.42?11.62 and 124.27?8.73, respectively. At 2, 3 and 4 months of
      gestation, the number of nestin-positive cells in the tongue muscles was
      12.50?3.17, 19.00?7.63, and 22.80?6.91, with expression intensity of
      119.99?24.02, 102.20?11.76, and 98.24?10.66, respectively. As the gestational age
      increased, the number of MAP-2-positive cell number continued to decline
      following a transient increase but the expression intensity kept increasing;
      nestin-positive cells increased continuously but the expression intensity kept
      decreasing in the embryonic or fetal tongue muscles. CONCLUSION: MAP-2 and nestin
      proteins are involved in the regulation of the development of tongue muscles in
      human embryos and fetuses.

PMID- 25613630
TI  - [Intracranial atherosclerotic middle cerebral arterial stenosis research based on
      3.0 Tesla high-resolution magnetic resonance imaging: recent progress].
AB  - Intracranial atherosclerotic disease (ICAD) of a major intracranial artery,
      including middle cerebral artery (MCA),basilar artery, is the most common causes
      of stroke and is associated with a high risk of recurrent stroke in China. The
      difficulty to treatment these high-risk disease is to identify high-risk stroke
      subgroups and to develop more effective treatments (aggressive medical
      therapy/endovascular therapy). With the benefits, including non-invasive, in
      vivo, and no-ionizing radiation, 3.0 Tesla high-resolution magnetic resonance
      imaging (HR MRI) could be used to stratify high-risk patients, monitor
      progression of disease, and evaluate clinical efficacy, based on MCA wall
      structure and plaque characteristic. HR MRI has the latency of predicting high
      risk patients benefit from endovascular therapy, having a broad application
      prospect during psot-SAMMPRIS era. The current research on MCA stenosis using HR
      MRI focuses on methodoiogy, diagnosis and differential diagnosis, etiology, and
      lacks of clinical efficiency evaluation and prognostic analysis of ICAD
      treatment, especially lacks the research on in-stent restenosis, which needs
      further investigation.

PMID- 25613631
TI  - [Effect of repeated hypoxic preconditioning on renal ischemia-reperfusion-induced
      hepatic dysfunction in rats].
AB  - OBJECTIVE: To explore the effect of repeated hypoxic preconditioning (RHP) on
      renal ischemia-reperfusion-induced hepatic dysfunction in rats and the underlying
      mechanism. METHODS: A total of 120 normal SD rats were randomly divided into 4
      groups (n=40), namely RHP surgical group, RHP sham-operated (RHPS) group,
      nonhypoxic surgical group (IRI group), and nonhypoxic sham-operated group (S
      group). The rats in the hypoxic groups were exposed to hypoxia in a hypoxic
      chamber for 5 days prior to establishment of renal ischemia-reperfusion model by
      resection of the right kidney and clamping the left renal hilum. Serum alanine
      aminotransferase (ALT), IL-17 A, TNF-a, liver superoxide dismutase (SOD) and
      nitric oxide (NO) were detected at 2, 8 and 24h after reperfusion, and Western
      blotting was used to determine the expression of p-PI3K and p-AKT;HE staining was
      used to observe the structural changes in the liver. RESULTS: Compared with IRI
      group, RHP group showed significantly milder hepatic damage, lower ALT levels and
      higher NO levels at 2, 8, and 24 after reperfusion (P<0.05); TNF-a levels were
      lowered at 24 h (P<0.05) and SOD increased at 8 h after the reperfusion (P<0.05).
      Compared with S group, IRI group and RHP group showed significantly higher IL-17A
      levels (P<0.05) but without significant difference between the latter two groups
      (P>0.05). The expressions of p-PI3K and P-Al<t in RHP group were significantly
      higher than those in IRI group (P<0.05), especially at 8 h after reperfusion
      (P<0.05). CONCLUSION: Repeated hypoxic preconditioning can attenuate hepatic
      injury induced by renal ischemia-reperfusion injury in rats.

PMID- 25613632
TI  - [Association of pro-B-type natriuretic peptide levels with heart rate variability
      in diabetic patients].
AB  - OBJECTIVE: To investigate the correlation between pro-B-type natriuretic peptide
      (NT-proBNP) and heart rate variability (HRV) in patients with diabetes. METHODS:
      HRV and NT-proBNP levels were assessed in 58 patients with diabetes.The time
      domain and frequency domain indices and the level of NT-proBNP were compared
      between patients with normal and abnormal HRV, and the correlation of HRV index
      and NT-proBNP was analyzed. RESULTS: The NT-proBNP level was significantly higher
      in patients with abnormal HRV than in those with normal HRV (320.2+/-88.3 vs
      80.4+/-25.2 pg/ml, P<0.01).The level of NT-proBNP was negatively correlated with
      SDNN (r=-0.55, P<0.05), triangle index (r=-0.52, P<0.05), LF (r=-0.62, P<0.01),
      and VLF (r=-0.56, P<0.05). CONCLUSION: NT-proBNP level is correlated with HRV,
      and an increased NT-proBNP indicates cardiac autonomic neuropathy in diabetic
      patients.

PMID- 25613633
TI  - [3T magnetic resonance T2 mapping for evaluation of cartilage repair after matrix
      associated autologous chondrocyte transplantation].
AB  - OBJECTIVE: To assess the value of magnetic resonance imaging (MRI) T2 mapping in
      quantitative evaluation of cartilage repair following matrix-associated
      autologous chondrocyte transplantation (MACT). METHODS: Six patients (with 9 plug
      cartilages) following MACT underwent MRI on a 3.0 Tesla MR scan system at 3, 6
      and 12 months after the surgery. The full-thickness and zonal areas (deep and
      superficial layers) T2 values were calculated for the repaired cartilage and
      control cartilage. RESULTS: The mean T2 values of the repaired cartilage after
      MACT were significantly higher than that of the control cartilages at 3 and 6
      months (P<0.05), but not at 12 months (P=0.063). At 6 and 12 months, the T2
      values of the superficial layers were significantly higher than those of the deep
      layers in the repaired cartilages (P<0.05). The zonal (deep and superficial
      layers) T2 values of the repaired cartilages decreased significantly over time at
      6 and 12 months as compared to those at 3 months after the surgery (P<0.05).
      CONCLUSION: MRI T2 mapping can serve as an important modality for assessing the
      repair of the articular cartilage following MACT.

PMID- 25613634
TI  - [Effect of supplementing qi, blood-activating and kidney-nourishing therapy on
      postoperative recovery in patients with lumber disc herniation].
AB  - OBJECTIVE: To investigate the effect of supplementing qi, activating blood
      circulation and tonifying kidney therapy on the postoperative outcomes of
      patients undergoing lumber intervertebral disc herniation. METHODS: From January
      2010 to May 2012, 120 patients with lumbar intervertebral disc herniation
      undergoing surgical treatment in Nanfang hospital were randomized into two equal
      groups to receive routine therapy (control group) and additional treatment with
      Yiqi Houxue Bushen Decoction (treatment group). The effect of the interventions
      was evaluated by assessing the Visual Analogue Scale(VAS), Japanese Orthopedic
      Association Scores (JOA), WHO Quality of Life-BREF (WHOQOL-BREF), length of
      hospital stay and adverse event. RESULTS: All the 120 patients were followed up
      and analyzed. Significant differences were found between the treatment and
      control groups in VAS, JOA Scores, and WHOQOL-BREF (P<0.01) at 2, 4, and 8 week
      and at 6 and 12 months after the surgery. At 6 and 12 months postoperatively, the
      JOA Scores (P<0.01), but not the VAS and WHOQOL-BREF, differed significantly
      between the two groups. CONCLUSION: Blood-activating and kidney-nourishing
      therapy is effective in promoting postoperative recovery and helps reduce the
      clinical symptoms and minimize the adverse events in patients undergoing surgery
      for lumber intervertebral disc herniation.

PMID- 25613635
TI  - [Effects of electro-acupuncture on expression of triggering receptor expressed on
      myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats].
AB  - OBJECTIVE: To investigate the effects of electro-acupuncture (EA) on the
      expression of triggering receptor expressed on myeloid cell (TREM)l in ankle
      joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Forty male SD
      rats were randomly divided into 4 groups: normal, AGA, medication and EA group,
      10 rats in each group. AGA model was established by induced monosodium urate
      (MSU) method, except the normal group. Tow days before AGA model was established,
      normal and AGA groups were lavaged with normal saline (20 ml/kg), medication
      group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave,
      9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun"
      (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes
      in dysfunction, and the content of TNF-alpha and IL-lbeta detected by ELISA, the
      expression of TREM-l detected by immunohistochemistry and western blot. RESULTS:
      Compared to the normal group, the AGA group of the dysfunction index increased
      significantly (P<0.01), the content of TNF-alpha and IL-lbeta increased
      significantly (P<0.05), the expression of TREM-l in synovial tissue increased
      significantly (P<0.05); the medication and EA groups compared to the AGA group,
      the dysfunction index decreased significantly (P<0.01), the content of TNF-alpha
      and IL-lbeta decreased significantly (P<0.05), the expression of TREM-l in
      synovial tissue decreased significantly (P<0.05); there were not statistically
      significant between the medication and EA group (P>0.05). CONCLUSION: EA treating
      AGA may be through down-regulating the expression of TREM -1 in synovial tissue.

PMID- 25613636
TI  - [Rituximab-induced interstitial pneumonitis: report of two cases and literature
      review].
AB  - We report two cases of rituximab (RTX)-induced interstitial pneumonia in two
      lymphoma patients receiving RTX treatment. Interstitial pneumonia was
      successfully managed in these two cases after a one-week-long intervention with
      corresponding treatments without affecting further treatment of the primary
      disease. RTX-induced interstitial pneumonia is characterized by a latent onset
      with an unclear pathological mechanism and absence of typical symptoms. High
      resolution CT scan can provide valuable evidence for early diagnosis of RTX
      induced interstitial pneumonia, which might be attributed partially to an
      increased susceptibility to P. jirovecii and fungal infection due to prolonged
      RTX treatment.

PMID- 25613637
TI  - Serious and long-term adverse events associated with the therapeutic and cosmetic
      use of botulinum toxin.
AB  - Although botulinum toxin is generally considered safe, its widespread use and the
      constantly expanded indications raise safety issues. This study aimed to review
      the serious and long-term adverse events associated with the therapeutic and
      cosmetic use of botulinum toxin. Serious adverse events included dysphagia,
      respiratory compromise, generalized muscle weakness, marked bilateral ptosis,
      pseudoaneurysm of the frontal branch of the temporal artery, necrotizing
      fasciitis, sarcoidal granuloma, Fournier gangrene, and cervical kyphosis. Death
      was attributed to botulism or anaphylactic shock. In conclusion, botulinum toxin
      may cause serious adverse events, which are more common after its therapeutic
      use, but can also be noticed after its cosmetic use. Thorough knowledge of the
      anatomy of the treated muscles and of the pharmacology of the drug is imperative
      to avoid serious adverse events.

PMID- 25613638
TI  - A comparative investigation on the effects of nitrogen-doping into graphene on
      enhancing the electrochemical performance of SnO2/graphene for sodium-ion
      batteries.
AB  - SnO2/nitrogen-doped graphene nanohybrids have been synthesized by an in situ
      hydrothermal method, during which the formation of SnO2 nanocrystals and nitrogen
      doping of graphene occur simultaneously. The as-prepared SnO2/nitrogen-doped
      graphene nanohybrids exhibit enhanced electrochemical performance for sodium-ion
      batteries compared to SnO2/graphene nanocomposites. A systematic comparison
      between SnO2/nitrogen-doped graphene nanohybrids and the SnO2/graphene
      counterpart as anode materials for sodium-ion batteries has been conducted. The
      comparison is in a reasonable framework, where SnO2/nitrogen-doped graphene
      nanohybrids and the SnO2/graphene counterpart have the same SnO2 ratio, similar
      SnO2 crystallinity and particle size, close surface area and pore size. The
      results clearly manifest that the improved electron transfer efficiency of
      SnO2/nitrogen-doped graphene due to nitrogen-doping plays a more important role
      than the increased electro-active sites within graphene network in enhancing the
      electro-activity of SnO2/nitrogen-doped graphene nanohybrids compared to the
      SnO2/graphene counterpart. In contrast to the previous reports which often
      ascribe the enhanced electro-activity of nitrogen-doped graphene based composites
      to two nitrogen-doping effects (improving the electron transfer efficiency and
      increasing electro-active sites within graphene networks) in one single
      declaration, this work is expected to provide more specific information for
      understanding the effects of nitrogen-doping into graphene on improving the
      electrochemical performance of graphene based composites. 

PMID- 25613639
TI  - A rare complication of radiofrequency ablation: skin burn.
AB  - Radiofrequency ablation is the first-line treatment for arrhythmias with high
      success and low complication rates. Skin burns have been reported rarely after
      electrophysiological procedures, especially procedures in which higher-power
      energy is used and multiple ablations are performed. Here, we report a case of
      skin burn that developed after radiofrequency ablation for ventricular
      tachycardia originating from the right ventricular outflow tract. 

PMID- 25613641
TI  - Ammonium photo-production by heterocytous cyanobacteria: potentials and
      constraints.
AB  - Over the last decades, production of microalgae and cyanobacteria has been
      developed for several applications, including novel foods, cosmetic ingredients
      and more recently biofuel. The sustainability of these promising developments can
      be hindered by some constraints, such as water and nutrient footprints. This
      review surveys data on N2-fixing cyanobacteria for biomass production and ways to
      induce and improve the excretion of ammonium within cultures under aerobic
      conditions. The nitrogenase complex is oxygen sensitive. Nevertheless, nitrogen
      fixation occurs under oxic conditions due to cyanobacteria-specific
      characteristics. For instance, in some cyanobacteria, the vegetative cell
      differentiation in heterocyts provides a well-adapted anaerobic microenvironment
      for nitrogenase protection. Therefore, cell cultures of oxygenic cyanobacteria
      have been grown in laboratory and pilot photobioreactors (Dasgupta et al., 2010;
      Fontes et al., 1987; Moreno et al., 2003; Nayak & Das, 2013). Biomass production
      under diazotrophic conditions has been shown to be controlled by environmental
      factors such as light intensity, temperature, aeration rate, and inorganic carbon
      concentration, also, more specifically, by the concentration of dissolved oxygen
      in the culture medium. Currently, there is little information regarding the
      production of extracellular ammonium by heterocytous cyanobacteria. This review
      compares the available data on maximum ammonium concentrations and analyses the
      specific rate production in cultures grown as free or immobilized filamentous
      cyanobacteria. Extracellular production of ammonium could be coupled, as
      suggested by recent research on non-diazotrophic cyanobacteria, to that of other
      high value metabolites. There is little information available regarding the
      possibility for using diazotrophic cyanobacteria as cellular factories may be in
      regard of the constraints due to nitrogen fixation. 

PMID- 25613640
TI  - Capsicum annuum transcription factor WRKYa positively regulates defense response
      upon TMV infection and is a substrate of CaMK1 and CaMK2.
AB  - Plants are constantly exposed to pathogens and environmental stresses. To
      minimize damage caused by these potentially harmful factors, plants respond by
      massive transcriptional reprogramming of various stress-related genes via major
      transcription factor families. One of the transcription factor families, WRKY,
      plays an important role in diverse stress response of plants and is often useful
      to generate genetically engineered crop plants. In this study, we carried out
      functional characterization of CaWRKYa encoding group I WRKY member, which is
      induced during hypersensitive response (HR) in hot pepper (Capsicum annuum) upon
      Tobacco mosaic virus (TMV) infection. CaWRKYa was involved in L-mediated
      resistance via transcriptional reprogramming of pathogenesis-related (PR) gene
      expression and affected HR upon TMV-P0 infection. CaWRKYa acts as a positive
      regulator of this defense system and could bind to the W-box of diverse PR genes
      promoters. Furthermore, we found Capsicum annuum mitogen-activated protein kinase
      1 (CaMK1) and 2 (CaMK2) interacted with CaWRKYa and phosphorylated the SP
      clusters but not the MAPK docking (D)-domain of CaWRKYa. Thus, these results
      demonstrated that CaWRKYa was regulated by CaMK1 and CaMK2 at the
      posttranslational level in hot pepper. 

PMID- 25613642
TI  - MiR-376a and histone deacetylation 9 form a regulatory circuitry in
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Our previous study has demonstrated that down-regulation of miR
      376a might contribute to the development of hepatocellular carcinoma (HCC), but
      the mechanism underlying this down-regulation remains obscure. METHODS/RESULTS:
      histone deacetylase (HDAC) inhibitor increased the level of miR-376a in L02 and
      Huh7 cells by up-regulating the acetylation level of histone 3 at the Maternally
      expressed 3 (Meg3) differentially methylated region (DMR). Interestingly, HDAC9,
      a histone deacetylase responsible for deacetylating lysine 18 of histone 3
      (H3K18), was identified as the target of miR-376a. In addition, HDAC9 siRNA
      increased the expression of miR-376a by up-regulating the global histone H3K18
      acetylation level, with Meg3 DMR included. Finally, miR-376a and HDAC9 were
      inversely correlated in HCC. CONCLUSION: HDAC9 plays an important role both as
      effects and targets of miR-376a.

PMID- 25613643
TI  - Medication Adherence and Health Outcomes of People Living with HIV Who Are Food
      Insecure and Prescribed Antiretrovirals That Should Be Taken with Food.
AB  - INTRODUCTION: Food insecurity is a well-established predictor of poor health
      outcomes. Antiretroviral therapies (ARTs) that should be taken with food to
      increase bioavailability may further challenge food insecure patients. This study
      examined factors associated with antiretroviral adherence and HIV viral
      suppression among people living with HIV who are food insecure and prescribed
      medications that require food. METHODS: A community sample of 313 men and 105
      women who experienced food insecurity in the previous month and were currently
      taking ART completed computerized interviews, urine screening for drug use,
      prospective biweekly unannounced pill count adherence assessments, and obtained
      their HIV viral load and CD4 cell counts from medical records. RESULTS:
      Individuals taking ART regimens that should be taken with food were significantly
      more likely to be unemployed, were living longer with an HIV diagnosis, had lower
      CD4 cell counts, poorer HIV suppression, and endorsed more beliefs that taking
      medications was necessary for their health. Multivariable regression models
      controlling for potential confounding factors showed that receiving ART that
      requires food was significantly related to poorer ART adherence and unsuppressed
      HIV in this food insecure sample. CONCLUSION: People living with HIV who are food
      insecure likely experience multiple facets of poverty that challenge their
      medication adherence, but food insecurity is the only such factor that is
      directly related to the pharmacokinetics of some antiretroviral medications.
      Achieving optimal treatment outcomes for HIV infection will require routine
      assessment of access to food when determining patient-tailored ART regimens.

PMID- 25613644
TI  - Using performance reference compound-corrected polyethylene passive samplers and
      caged bivalves to measure hydrophobic contaminants of concern in urban coastal
      seawaters.
AB  - Low-density polyethylene (PE) passive samplers containing performance reference
      compounds (PRCs) were deployed at multiple depths in two urban coastal marine
      locations to estimate dissolved concentrations of hydrophobic organic
      contaminants (HOCs), including dichlorodiphenyltrichloroethane (DDT) and its
      metabolites, polychlorinated biphenyl (PCB) congeners, and polybrominated flame
      retardants. PE samplers pre-loaded with PRCs were deployed at the surface, mid
      column, and near bottom at sites representing the nearshore continental shelf off
      southern California (Santa Monica Bay, USA) and a mega commercial port (Los
      Angeles Harbor). After correcting for fractional equilibration using PRCs,
      concentrations ranged up to 100 pg L(-1) for PCBs and polybrominated diphenyl
      ethers (PBDEs), 500 pg L(-1) for DDMU and 300 pg L(-1) for DDNU, and to 1000 pg
      L(-1) for p,p'-DDE. Seawater concentrations of DDTs and PCBs increased with
      depth, suggesting that bed sediments serve as the source of water column HOCs in
      Santa Monica Bay. In contrast, no discernable pattern between surface and near
      bottom concentrations in Los Angeles Harbor was observed, which were also several
      fold lower (DDTs: 45-300 pg L(-1), PCBs: 5-50 pg L(-1)) than those in Santa
      Monica Bay (DDTs: 2-1100 pg L(-1), PCBs: 2-250 pg L(-1)). Accumulation by mussels
      co-deployed with the PE samplers at select sites was strongly correlated with PE
      estimated seawater concentrations, providing further evidence that these samplers
      are a viable alternative for monitoring of HOC exposure. Fractional equilibration
      observed with the PRCs increased with decreasing PRC molar volume indicating the
      importance of target compound physicochemical properties when estimating water
      column concentrations using passive samplers in situ.

PMID- 25613645
TI  - The role of the right frontal eye field in overt visual attention deployment as
      assessed by free visual exploration.
AB  - The frontal eye field (FEF) is known to be involved in saccade generation and
      visual attention control. Studies applying covert attentional orienting paradigms
      have shown that the right FEF is involved in attentional shifts to both the left
      and the right hemifield. In the current study, we aimed at examining the effects
      of inhibitory continuous theta burst (cTBS) transcranial magnetic stimulation
      over the right FEF on overt attentional orienting, as measured by a free visual
      exploration paradigm. In forty-two healthy subjects, free visual exploration of
      naturalistic pictures was tested in three conditions: (1) after cTBS over the
      right FEF; (2) after cTBS over a control site (vertex); and, (3) without any
      stimulation. The results showed that cTBS over the right FEF-but not cTBS over
      the vertex-triggered significant changes in the spatial distribution of the
      cumulative fixation duration. Compared to the group without stimulation and the
      group with cTBS over the vertex, cTBS over the right FEF decreased cumulative
      fixation duration in the left and in the right peripheral regions, and increased
      cumulative fixation duration in the central region. The present study supports
      the view that the right FEF is involved in the bilateral control of not only
      covert, but also of overt, peripheral visual attention. 

PMID- 25613647
TI  - Attention that covers letters is necessary for the left-lateralization of an
      early print-tuned ERP in Japanese hiragana.
AB  - Extensive experience with reading develops expertise in acquiring information
      from print, and this is reflected in specific enhancement of the left-lateralized
      N170 component in event-related potentials. The N170 is generally considered to
      reflect visual/orthographic processing; while modulations of its left
      lateralization related to phonological processes have also been indicated.
      However, in our previous study, N170-like response to Hiragana strings lacked
      left-lateralization when the stimuli were completely task-irrelevant in rapid
      presentation sequences [Okumura et al. (2014). Early print-tuned ERP response
      with minimal involvement of linguistic processing in Japanese Hiragana strings.
      Neuroreport 25, 410-414]. This suggests that, despite the highly transparent
      character-to-syllable correspondence, the phonological mapping of Hiragana
      strings requires some kind of attention toward print. To verify this notion, the
      present study examined ERPs under the same experimental condition as in the
      previous study, except that the task required attention to a stimulus attribute
      (i.e., color). As a result, Hiragana words and nonwords elicited left-lateralized
      negative deflection in the occipito-temporal region during 130-170ms post
      stimulus in comparison to symbol strings, but only when the print had a narrow
      intercharacter spacing. Moreover, we observed the enhancement of very early
      occipital ERP in response to words during 70-100ms. The present results suggest
      that visual attention plays a role in early print processing, which may
      contribute to our understanding of the mechanisms that underlie expert as well as
      impaired reading. 

PMID- 25613646
TI  - A study on the specificity of the association between hippocampal volume and
      delayed primacy performance in cognitively intact elderly individuals.
AB  - Delayed recall at the primacy position (first few items on a list) has been shown
      to predict cognitive decline in cognitively intact elderly participants, with
      poorer delayed primacy performance associated with more pronounced generalized
      cognitive decline during follow-up. We have previously suggested that this
      association is due to delayed primacy performance indexing memory consolidation,
      which in turn is thought to depend upon hippocampal function. Here, we test the
      hypothesis that hippocampal size is associated with delayed primacy performance
      in cognitively intact elderly individuals. Data were analyzed from a group (N=81)
      of cognitively intact participants, aged 60 or above. Serial position performance
      was measured with the Buschke selective reminding test (BSRT). Hippocampal size
      was automatically measured via MRI, and unbiased voxel-based analyses were also
      conducted to explore further regional specificity of memory performance. We
      conducted regression analyses of hippocampus volumes on serial position
      performance; other predictors included age, family history of Alzheimer's disease
      (AD), APOE epsilon4 status, education, and total intracranial volume. Our results
      collectively suggest that there is a preferential association between hippocampal
      volume and delayed primacy performance. These findings are consistent with the
      hypothesis that delayed primacy consolidation is associated with hippocampal
      size, and shed light on the relationship between delayed primacy performance and
      generalized cognitive decline in cognitively intact individuals, suggesting that
      delayed primacy consolidation may serve as a sensitive marker of hippocampal
      health in these individuals. 

PMID- 25613648
TI  - Commentary: the effects of psychological stress on microglial cells in the brain.
AB  - Psychological stress leads to activation and proliferation of microglial cells in
      different brain regions. These effects are mediated by inflammatory cytokines, as
      well as stress hormones including glucocorticoids and norepinephrine. Eliminating
      microglia from the nervous system or blocking their activation prevented the
      stress-induced impairments on brain cognitive functions. We conclude that
      microglial cells are important meditators underlying anti-depression therapies. 

PMID- 25613650
TI  - Note from the editors: Eurosurveillance--an authoritative information source on
      infectious diseases.

PMID- 25613649
TI  - Laboratory blood analysis in Strigiformes-Part II: plasma biochemistry reference
      intervals and agreement between the Abaxis Vetscan V2 and the Roche Cobas c501.
AB  - BACKGROUND: Limited plasma biochemical information is available in Strigiformes.
      Only one study investigated the agreement between a point-of-care with a
      reference laboratory analyzer for biochemistry variables in birds. OBJECTIVES:
      The objective was to report reference intervals (RI) for plasma biochemistry
      variables in Strigiformes, and to assess agreement between the Abaxis Vetscan V2
      and Roche Cobas c501. METHODS: A prospective study was designed to assess plasma
      biochemistry RI for concentration of calcium, phosphorus, total protein, albumin,
      globulin, glucose, bilirubin, uric acid, bile acids, sodium, potassium, and
      chloride, and activities of AST, GGT, CK, amylase, lipase, LDH, and GLDH. In
      addition, the agreement between the Vetscan and the Cobas in owl species was
      assessed. RESULTS: A total of 190 individuals were sampled belonging to 12
      Strigiformes species including Barn Owls, Barred Owls, Great Horned Owls,
      Eurasian Eagle Owls, Spectacled Owls, Eastern Screech Owls, Long-Eared Owls,
      Short-Eared Owls, Great Gray Owls, Snowy Owls, Northern Saw-Whet Owls, and
      Northern Hawk-Owls. Order-, species-, and method-specific RI were determined on
      both analyzers. Although Vetscan data were not equivalent to the Cobas, 4
      analytes (glucose, AST, CK, and total protein, with correction for bias) were
      within acceptable agreement, 3 analytes (uric acid, calcium, and phosphorus) were
      within close agreement, and the remaining analytes were in strong disagreement.
      Species-specific differences were observed notably for the concentration of
      glucose in Barn Owls and electrolytes in Northern Saw-Whet Owls. CONCLUSIONS:
      Overall, this study suggests that the Vetscan has acceptable clinical performance
      in Strigiformes for some analytes and highlights discrepancies for several
      analytes.

PMID- 25613652
TI  - EbolaTracks: an automated SMS system for monitoring persons potentially exposed
      to Ebola virus disease.
AB  - We report development and implementation of a short message service (SMS)-based
      system to facilitate active monitoring of persons potentially exposed to Ebola
      virus disease (EVD), whether returning from EVD-affected countries, or contacts
      of local cases, should they occur. The system solicits information on symptoms
      and temperature twice daily. We demonstrated proof-of-concept; however this
      system would likely be even more useful where there are many local contacts to
      confirmed EVD cases or travellers from EVD-affected countries.

PMID- 25613651
TI  - First secondary case of Ebola outside Africa: epidemiological characteristics and
      contact monitoring, Spain, September to November 2014.
AB  - On 6 October 2014, a case of Ebola virus disease (EVD) acquired outside Africa
      was detected in Madrid in a healthcare worker who had attended to a repatriated
      Spanish missionary and used proper personal protective equipment. The patient
      presented with fever <38.6  degrees C without other EVD-compatible symptoms in
      the days before diagnosis. No case of EVD was identified in the 232 contacts
      investigated. The experience has led to the modification of national protocols.

PMID- 25613653
TI  - Assessing the risk of measles resurgence in a highly vaccinated population:
      Belgium anno 2013.
AB  - Despite long-standing two-dose measles-mumps-rubella (MMR) vaccination, measles
      outbreaks still occur in highly vaccinated European populations. For instance,
      large measles outbreaks occurred in France (2008-13), the United Kingdom (2012
      13) and the Netherlands (2012). Based on a multicohort model approach, using
      spatial serological survey data, MMR vaccination coverage data and data on social
      contacts, we found effective reproduction numbers significantly higher than 1 for
      measles in Belgium. This indicates that at one of the expected re-introductions,
      a measles outbreak is likely to spread, especially when it occurs during school
      term. The predicted average effective reproduction number increased over a 30
      year time span from 1.3 to 2.2 and from 1.9 to 3.2 for basic reproduction numbers
      of 12 and 18, respectively. The expected relative measles incidence was highest
      in infants under one year of age, in adolescents and young adults. In conclusion,
      gradually increasing proportions of susceptible adolescents and young adults
      provide through their highly active social life an avenue for measles to resurge
      in large outbreaks upon re-introduction in Belgium, especially during school
      terms. Infants form an important vulnerable group during future measles
      outbreaks.

PMID- 25613654
TI  - European Union SHIPSAN ACT joint action: preparedness for the response to Ebola
      virus disease in the maritime transport sector.

PMID- 25613658
TI  - Erratum for euro surveill. 2014;19(48).

PMID- 25613659
TI  - Relevance of Five-Factor Model personality traits for obsessive-compulsive
      symptoms in patients with psychotic disorders and their un-affected siblings.
AB  - High rates of obsessive-compulsive symptoms (OCS) in schizophrenia require
      pathogenic explanations. Personality traits may represent risk and resiliency
      factors for the development of mental disorders and their comorbidities. The aim
      of the present study was to explore the associations between Five-Factor Model
      (FFM) personality traits and the liability for OCS in patients with psychotic
      disorders and in their un-affected siblings. FFM traits, occurrence and severity
      of OCS and (subclinical) psychotic symptoms were assessed in 208 patients and in
      281 siblings. Differences in FFM traits between participants with vs. without
      comorbid OCS were examined and the predictive value of FFM traits on group
      categorization was evaluated. Associations between FFM traits and OCS severity
      were investigated. Patients and siblings with OCS showed significantly higher
      Neuroticism compared to their counterparts without OCS. Neuroticism was
      positively associated with higher OCS severity and significantly predicted group
      assignment in both patients and in siblings. Patients with comorbid OCS presented
      with lower scores on Extraversion and Conscientiousness. Higher Neuroticism, and
      to a lesser degree lower Extraversion and Conscientiousness might add to the
      vulnerability of patients with a psychotic disorder to also develop OCS. Future
      prospective studies are needed to elucidate proposed personality-psychopathology
      interrelations and possible mediating factors. 

PMID- 25613660
TI  - Factorial structure of the 20-item Toronto Alexithymia Scale in a large sample of
      somatoform patients.
AB  - Although a strong association between alexithymia and somatization has been
      postulated in numerous studies, no systematic study has investigated the
      psychometric properties of the 20-item Toronto Alexithymia Scale (TAS-20) in a
      sample of patients with somatoform disorder yet. The purpose of this study was to
      ensure a valid assessment by the German version of the TAS-20 in somatoform
      samples. We investigated whether the original three-factor model proposed by
      Bagby et al. (1994a), which is widely used in clinical research and practice, is
      replicable in a large sample of somatoform patients (n=806). Using confirmatory
      factor analysis (CFA) the goodness-of-fit of the originally proposed factor
      structure was compared to three factor models generated with exploratory factor
      analysis (EFA) and other factorial solutions derived from the literature. Our
      results demonstrate that the original three-factor model is not replicable in
      somatoform patients. Instead, the four-factor model by Franz et al. (2001b)
      described the data best. However, none of the models met all criteria of
      confirmatory factor analysis. Our results indicate that the three-factor model is
      not robust in the German version of the TAS-20. At this state of research we
      recommend to use the TAS-20 sum-score as a measure of alexithymia in somatoform
      patients in clinical practice. 

PMID- 25613661
TI  - Efficacy of cognitive-behavioral therapy for obsessive-compulsive disorder.
AB  - Cognitive-behavioral therapy (CBT), which encompasses exposure with response
      prevention (ERP) and cognitive therapy, has demonstrated efficacy in the
      treatment of obsessive-compulsive disorder (OCD). However, the samples studied
      (reflecting the heterogeneity of OCD), the interventions examined (reflecting the
      heterogeneity of CBT), and the definitions of treatment response vary
      considerably across studies. This review examined the meta-analyses conducted on
      ERP and cognitive therapy (CT) for OCD. Also examined was the available research
      on long-term outcome associated with ERP and CT. The available research indicates
      that ERP is the first line evidence based psychotherapeutic treatment for OCD and
      that concurrent administration of cognitive therapy that targets specific symptom
      related difficulties characteristic of OCD may improve tolerance of distress,
      symptom-related dysfunctional beliefs, adherence to treatment, and reduce drop
      out. Recommendations are provided for treatment delivery for OCD in general
      practice and other service delivery settings. The literature suggests that ERP
      and CT may be delivered in a wide range of clinical settings. Although the data
      are not extensive, the available research suggests that treatment gains following
      ERP are durable. Suggestions for future research to refine therapeutic outcome
      are also considered. 

PMID- 25613662
TI  - Sparse factors for the positive and negative syndrome scale: which symptoms and
      stage of illness?
AB  - The Positive and Negative Syndrome Scale (PANSS) is frequently described with
      five latent factors, yet published factor models consistently fail to replicate
      across samples and related disorders. We hypothesize that (1) a subset of the
      PANSS, instead of the entire PANSS scale, would produce the most replicable five
      factor models across samples, and that (2) the PANSS factor structure may be
      different depending on the treatment phase, influenced by the responsiveness of
      the positive symptoms to treatment. Using exploratory factor analysis,
      confirmatory factor analysis and cross validation on baseline and post-treatment
      observations from 3647 schizophrenia patients, we show that five-factor models
      fit best across samples when substantial subsets of the PANSS items are removed.
      The optimal model at baseline (five factors) omits 12 items: Motor Retardation,
      Grandiosity, Somatic Concern, Lack of Judgment and Insight, Difficulty in
      Abstract Thinking, Mannerisms and Posturing, Disturbance of Volition,
      Preoccupation, Disorientation, Excitement, Guilt Feelings and Depression. The
      PANSS factor models fit differently before and after patients have been treated.
      Patients with larger treatment response in positive symptoms have larger
      variations in factor structure across treatment stage than the less responsive
      patients. Negative symptom scores better predict the positive symptoms scores
      after treatment than before treatment. We conclude that sparse factor models
      replicate better on new samples, and the underlying disease structure of
      Schizophrenia changes upon treatment. 

PMID- 25613663
TI  - Trends in total knee arthroplasty implant utilization.
AB  - The incidence of total knee arthroplasty (TKA) has increased alongside our
      knowledge of knee physiology, kinematics, and technology resulting in an
      evolution of TKA implants. This study examines the trends in TKA implant
      utilization. Data was extracted from The Orthopedic Research Network to evaluate
      trends in level of constraint, fixed vs. mobile bearing, fixation, and type of
      polyethylene in primary TKAs. In 2012, 88% used cemented femoral and tibial
      implants, and 96% involved patellar resurfacing. 38% of implants were cruciate
      retaining, 53% posterior stabilized or condylar stabilized, 3% constrained. 91%
      were fixed-bearing, 7% mobile-bearing. 52% of tibial inserts were HXLPE. TKA
      implant trends demonstrate a preference for cemented femoral and tibial
      components, patellar resurfacing, fixed-bearing constructs, metal-backed tibial
      components, patellar resurfacing, and increased usage of HXLPE liners. 

PMID- 25613664
TI  - Comparison of outcomes of patients with left ventricular ejection fractions <=30%
      versus >=30% having transcatheter aortic valve implantation (from the German
      Transcatheter Aortic Valve Interventions Registry).
AB  - Transcatheter aortic valve implantation (TAVI) is rapidly evolving in Germany.
      Especially severe reduced left ventricular ejection fraction (LVEF) is known as a
      prominent risk factor for adverse outcome in open heart surgery. Thus, the data
      of the prospective multicenter German Transcatheter Aortic Valve Interventions
      Registry were analyzed for outcomes in patients with severe depressed LVEF. Data
      of 1,432 patients were consecutively collected after transcatheter aortic valve
      implantation. Patients were divided into 2 groups (A: LVEF <=30%, n = 169, age
      79.9 +/- 6.7 years, logES 34.2 +/- 17.8%; B: LVEF >30%, n = 1,263, age 82.0 +/-
      6.1 years, logES 18.9 +/- 12.0%), and procedural success rates, New York Heart
      Association classification, and quality of life were compared at 30 days and 1
      year, respectively. Technical success was achieved in 95.9% (A) and 97.6% (B).
      Survival and the New York Heart Association classification at 30 days
      demonstrated an excellent outcome in both groups. There was a significant
      improvement according to the self-assessment in health condition (0 to 100 scale)
      with a much larger gain in group A (28 vs 19 patients, p <0.0001). Nevertheless,
      low cardiac output syndrome (12.3% vs 5.9%, p <0.01) and resuscitation (10.4% vs
      5.6%, p <0.05) were more frequently seen in group A, contributing to a higher
      mortality at 30 days (14.3% vs 7.2%) and 1 year (33.7% vs 18.1%, p <0.001). In
      conclusion, this real-world registry demonstrated a comparably high success rate
      for patients with severe reduced LVEF and an early improvement in functional
      status as demonstrated by substantial benefit, despite a doubled postprocedural
      mortality. 

PMID- 25613665
TI  - Meta-analysis appraising high maintenance dose clopidogrel in patients who
      underwent percutaneous coronary intervention with and without high on-clopidogrel
      platelet reactivity.
AB  - The CURRENT-OASIS 7 (Clopidogrel and Aspirin Optimal Dose Usage to Reduce
      Recurrent Events-Seventh Organization to Assess Strategies in Ischemic Symptoms)
      trial showed that a 7-day 150-mg maintenance dose (MD) clopidogrel could reduce
      cardiovascular events in subgroup patients who underwent percutaneous coronary
      intervention (PCI) compared with the 75 mg/day regimen, although whether
      prolonging the high MD clopidogrel (>=150 mg) treatment period to at least 4
      weeks can reduce major adverse cardiac events in the patients who underwent PCI
      with and without high on-clopidogrel platelet reactivity (HPR) is still
      controversial. We searched Pubmed, Embase, and Cochrane Library from inception
      until September 2014 for randomized controlled trials that compared high versus
      standard MD clopidogrel in patients who underwent PCI. Seventeen trials involving
      4,822 patients who underwent PCI included 2,879 patients who were allocated to
      the "HPR patients" subgroup and 1,943 to the "native patients" subgroup without
      paying attention to the clopidogrel reactivity before randomization. Compared
      with the standard therapy, the high MD clopidogrel was associated with a
      significant reduction in the risk of major adverse cardiac events (odds ratio
      [OR] 0.52, 95% confidence interval [CI] 0.39 to 0.71, p <0.0001) in patients who
      underwent PCI. The HPR patients subgroup was also benefited from such high MD
      treatment (OR 0.54, 95% CI 0.38 to 0.77, p = 0.0007). The observed benefits were
      mainly attributed to treatment-associated reduction in stent thrombosis (OR 0.43,
      95% CI 0.23 to 0.78, p = 0.006) and target vessel revascularization (OR 0.38, 95%
      CI 0.20 to 0.74, p = 0.004). There was no difference in the rate of major/minor
      bleeding event between the high and standard MD group (OR 0.80, 95% CI 0.56 to
      1.13, p = 0.21). In conclusion, the efficacy and safety of at least 4 weeks' high
      MD clopidogrel is greater than that of standard therapy for patients who
      underwent PCI with and without HPR.

PMID- 25613666
TI  - Alteration of the miRNA expression profile in male porcine anterior pituitary
      cells in response to GHRH and CST and analysis of the potential roles for miRNAs
      in regulating GH.
AB  - OBJECTIVE: Growth hormone releasing hormone (GHRH) is a major positive regulator
      of growth hormone (GH) in the anterior pituitary gland, while cortistatin's (CST)
      role is negative. miRNAs (microRNAs or miRs) are small RNA molecules modulating
      gene expression at the post-transcriptional level. However, little is known about
      the function of miRNAs in the regulation of GH synthesis and/or secretion. This
      study investigated potential functional miRNAs involved in GH secretion in the
      normal porcine pituitary. DESIGN: Primary porcine anterior pituitary cells were
      cultivated and then treated with 10 nmol/L GHRH and 100 nmol/L CST, respectively.
      The effects of GHRH and CST on GH secretion were determined using RIA. miRNA
      microarrays were employed to analyze miRNA expression after treatment and then
      differentially expressed miRNAs were screened. Bioinformatics analysis was used
      to analyze the potential targets in growth hormone regulation of altered miRNAs.
      Furthermore, functional experiments were conducted to study the function of ssc
      let-7c. RESULTS: GHRH significantly promoted GH secretion, while CST suppressed
      GH secretion. 19 and 35 differentially expressed miRNAs were identified in
      response to GHRH and CST treatments respectively. Verification of 5 randomly
      selected miRNAs by quantitative real-time PCR (qRT-PCR) showed similar changes
      with microarray analysis. Target analysis showed that some miRNAs may be involved
      in GH secretion-related pathways. Importantly, ssc-let-7c was predicted to target
      GH1 and GHRHR mRNA 3'untranslated regions (3'UTRs), which was supported by
      luciferase reporter assay. Furthermore, functional experimental results showed
      that ssc-let-7c was involved in GH secretion regulation, and overexpression of
      ssc-let-7c inhibited GH secretion in porcine anterior pituitary cells.
      CONCLUSIONS: GHRH and CST modulated porcine pituitary cell miRNA expression.
      Bioinformatics analysis revealed a complicated network among differentially
      expressed miRNAs, GH regulation-related genes and hormones. More interestingly,
      ssc-let-7c inhibited both GH1 and GHRHR mRNA 3'UTR reporter vectors' luciferase
      activity and overexpression of ssc-let-7c led to a decrease of GH secretion.

PMID- 25613667
TI  - Isolation and characteristic analysis of a novel strain H7N9 of avian influenza
      virus A from a patient with influenza-like symptoms in China.
AB  - A novel H7N9 virus (A/Changsha/1/2013(H7N9)) identified through routine
      examination in the influenza network laboratory was analyzed retrospectively. The
      gene sequences of A/Changsha/1/2013(H7N9) were highly homologous to other viruses
      isolated in mainland China. Mutations of Q226L and G186V were found in the
      hemagglutinin protein (HA). Amino acid deletions were found at positions 69-73 of
      the neuraminidase protein (NA) and 218-230 of the non-structural protein (NS1).
      All viral genes except PB1 were essentially identical to the sequences of other
      Chinese influenza A H7N9 isolates. Overall, A/Changsha/1/2013(H7N9) is highly
      homologous to other H7N9 avian influenza viruses isolated in mainland China. 

PMID- 25613669
TI  - Percutaneous BioOrganic Sealing of Duodenal Fistulas: Case Report and Review of
      Biological Sealants with Potential Use in Interventional Radiology.
AB  - Biological sealants are being increasingly used in a variety of surgical
      specialties for their hemostatic and sealing capabilities. However, their use in
      interventional radiology has not been widely reported. The authors describe a
      case of duodenal perforation occurring after 15 years of gastric bypass surgery,
      in whom surgical diversion was unsuccessfully attempted and the leakage was
      successfully controlled using percutaneous administration of a combination of
      biological and organic sealants.

PMID- 25613668
TI  - TM-233, a novel analog of 1'-acetoxychavicol acetate, induces cell death in
      myeloma cells by inhibiting both JAK/STAT and proteasome activities.
AB  - Although the introduction of bortezomib and immunomodulatory drugs has led to
      improved outcomes in patients with multiple myeloma, the disease remains
      incurable. In an effort to identify more potent and well-tolerated agents for
      myeloma, we have previously reported that 1'-acetoxychavicol acetate (ACA), a
      natural condiment from South-East Asia, induces apoptotic cell death of myeloma
      cells in vitro and in vivo through inhibition of NF-kappaB-related functions.
      Searching for more potent NF-kappaB inhibitors, we developed several ACA analogs
      based on quantitative structure-activity relationship analysis. TM-233, one of
      these ACA analogs, inhibited cellular proliferation and induced cell death in
      various myeloma cell lines with a lower IC50 than ACA. Treatment with TM-233
      inhibited constitutive activation of JAK2 and STAT3, and then downregulated the
      expression of anti-apoptotic Mcl-1 protein, but not Bcl-2 and Bcl-xL proteins. In
      addition, TM-233 rapidly decreased the nuclear expression of NF-kappaB and also
      decreased the accumulation of cytosolic NF-kappaB. We also examined the effects
      of TM-233 on bortezomib-resistant myeloma cells that we recently established, KMS
      11/BTZ and OPM-2/BTZ. TM-233, but not bortezomib, inhibited cellular
      proliferation and induced cell death in KMS-11/BTZ and OPM-2/BTZ cells.
      Interestingly, the combination of TM-233 and bortezomib significantly induced
      cell death in these bortezomib-resistant myeloma cells through inhibition of NF
      kappaB activity. These results indicate that TM-233 could overcome bortezomib
      resistance in myeloma cells mediated through different mechanisms, possibly
      inhibiting the JAK/STAT pathway. In conclusion, TM-233 might be a more potent NF
      kappaB inhibitor than ACA, and could overcome bortezomib resistance in myeloma
      cells. 

PMID- 25613670
TI  - Transjugular Intrahepatic Portosystemic Shunt Placement During Pregnancy: A Case
      Series of Five Patients.
AB  - BACKGROUND AND AIMS: Complications of portal hypertension, such as variceal
      hemorrhage and ascites, are associated with significant increases in both
      mortality and complications during pregnancy. Transjugular intrahepatic
      portosystemic shunt (TIPS) is a well-established procedure for treating portal
      hypertension, but the safety of TIPS during pregnancy is largely unknown. In this
      series, we review five patients who underwent TIPS placement while pregnant and
      describe their clinical outcomes. METHODS: Five pregnant patients with cirrhosis
      and portal hypertension underwent elective TIPS for complications of portal
      hypertension (four for secondary prevention of variceal bleeding and one for
      refractory ascites). Outcomes measured were recurrent bleeding episodes or need
      for further paracenteses during pregnancy, estimated radiation dose to the fetus
      and gestational age at delivery. All patients were followed after delivery to
      evaluate technical and clinical success of the procedure. RESULTS: All five
      patients survived pregnancy and went on to deliver successfully. When TIPS was
      performed for secondary prevention of variceal bleeding (n = 4), no patients
      demonstrated variceal bleeding after TIPS placement. When TIPS was performed for
      refractory ascites (n = 1), no further paracenteses were required. All patients
      delivered successfully, albeit prematurely. Average radiation dose estimated to
      the fetus was 16.3 mGy. CONCLUSIONS: This series suggests that TIPS can be
      performed in selective pregnant patients with portal hypertension, with little
      added risk to the mother or fetus.

PMID- 25613671
TI  - Determining the minimal clinically important difference and responsiveness of the
      Dermatology Life Quality Index (DLQI): further data.
AB  - AIMS: To determine the minimal clinically important difference (MCID) of the
      Dermatology Life Quality Index (DLQI) and its responsiveness to change in
      inflammatory skin diseases. METHODS: A longitudinal study: at stage 1, patients
      completed the DLQI and a disease severity global question; at stage 2, a global
      rating of change in quality of life (QoL; Global Rating of Change Questionnaire,
      GRCQ) was added and used as an anchor to measure the MCID of the DLQI. RESULTS:
      192 patients completed stage 1 and 107 completed stage 2. The mean DLQI score at
      stage 1 was 9.8 and 7.4 at stage 2 with a mean change of 2.4 (p < 0.0001). 31
      patients experienced a 'small change' in their QoL (+/-3 and +/-2) on the GRCQ.
      The mean corresponding change in DLQI scores was 3.3, which is regarded as the
      approximate MCID. CONCLUSIONS: Previous estimates of the MCID of the DLQI have
      varied from 3 to 5. Although this study demonstrated a MCID of 3.3, we recommend
      that the MCID in inflammatory skin diseases should be 4.

PMID- 25613672
TI  - Pinpointing mechanochemical bond rupture by embedding the mechanophore into a
      macrocycle.
AB  - Mechanophores contain a mechanically labile bond that can be broken by an
      external mechanical force. Quantitative measurement and control of the applied
      force is possible through atomic force microscopy (AFM). A macrocycle was
      synthesized that contains both the mechanophore and an aliphatic chain that acts
      as a "safety line" upon bond breaking. This ring-opening mechanophore unit is
      linked to poly(ethylene glycol) spacers, which allow investigation by single
      molecule force spectroscopy. The length increase upon rupture of the mechanophore
      was measured and compared with quantum chemical calculations. 

PMID- 25613673
TI  - Correlation between Choline Peak at MR Spectroscopy and Calcium-Sensing Receptor
      Expression Level in Breast Cancer: A Preliminary Clinical Study.
AB  - PURPOSE: The calcium-sensing receptor (CaSR) is overexpressed in many
      pathological states including breast cancer. Since choline kinase may be
      activated in breast cancer cells by CaSR resulting in increased phosphocholine
      production, we sought to correlate the total choline peak in breast lesions as
      measured by in vivo proton magnetic resonance spectroscopy ((1)H-MRS) with the
      CaSR expression levels in surgical specimens. PROCEDURES: Thirty-six patients
      with breast lesions were MR scanned at 3T scanner. Tumour morphology and DCE-MR
      kinetics were evaluated. (1)H-MRS was applied for Cho detection and compared with
      the CaSR immunohistochemistry analysis (score 0-5) on surgical breast specimens.
      RESULTS: Thirty-four lesions demonstrated a DCE malignant kinetics curve (types 2
      and 3), while two lesions showed a benign (type 1). Twenty of the 23 breast
      cancer lesions (87%) with a consistent Cho peak expressed a CaSR score of 3-5,
      and ten of the 11 breast lesions negative for Cho (91%) had a CaSR score of 1-2.
      The two benign lesions showed a non-uniform/weak intense expression of the CaSR
      (score 3) with a consistent Cho peak. CONCLUSIONS: The presence or absence of
      choline peak evaluated by (1)H-MRS, well correlated with the expression of CaSR
      in patients with breast lesions (p < 0.01), supports the hypothesis that CaSR may
      play an important role in the production of choline in breast cancer.

PMID- 25613674
TI  - Optical coherence tomographic observation of in-stent neoatherosclerosis in
      lesions with more than 50% neointimal area stenosis after second-generation drug
      eluting stent implantation.
AB  - BACKGROUND: Despite the enhanced properties of the second-generation drug-eluting
      stent (DES), its association with neoatherosclerosis has not been sufficiently
      evaluated. Therefore, we sought to evaluate and compare neoatherosclerosis in
      second-generation DESs to first-generation DESs. METHODS AND RESULTS: A total of
      212 DES-treated patients with >50% percent neointimal cross-sectional area
      stenosis were retrospectively enrolled from the Korean multicenter optical
      coherence tomography (OCT) registry. Within this population, 111 patients had a
      second-generation DES (40 zotarolimus, 36 everolimus, and 35 biolimus) and 101
      patients had a first-generation (65 sirolimus and 36 paclitaxel) DES.
      Neoatherosclerosis on OCT was defined as neointima formation with the presence of
      lipids or calcification. OCT-determined neoatherosclerosis was identified in
      27.4% (58/212) of all DES-treated lesions. The frequency of neoatherosclerosis
      increased with the stent age. Stent age was shorter in the second-generation DES
      group (12.4 months versus 55.4 months, P<0.001), and neoatherosclerosis was less
      frequently observed in that group (10.8% versus 45.5%, P<0.001). However, after
      adjusting for cardiovascular risk factors, chronic kidney disease (odds ratio,
      4.113; 95% confidence interval, 1.086-15.575; P=0.037), >70 mg/dL of low-density
      cholesterol at follow-up OCT (odds ratio, 2.532; 95% confidence interval, 1.054
      6.084; P=0.038), and stent age (odds ratio, 1.710; 95% confidence interval, 1.403
      2.084; P<0.001) were all independent predictors for neoatherosclerosis, whereas
      the type of DES (first- versus second-generation) was not. Patients with
      neoatherosclerosis showed a higher rate of acute coronary syndrome at follow-up
      OCT (19.0% versus 3.9%, respectively, P=0.001). CONCLUSIONS: The second
      generation DES is not more protective against neoatherosclerosis compared with
      the first-generation DES.

PMID- 25613675
TI  - The effect of a diet containing 70% protein from plants on mineral metabolism and
      musculoskeletal health in chronic kidney disease.
AB  - BACKGROUND: Chronic Kidney Disease (CKD) is associated with alterations in
      phosphorus excretion, and increases in fibroblast growth factor (FGF23) and
      parathyroid hormone (PTH). Plant protein-based phytate-bound phosphorus, is less
      bioavailable than that from animal sources. Our one-week study that was conducted
      previously showed that a nearly 100% plant protein-based diet benefits mineral
      metabolism in CKD; however, this diet may not be acceptable to patients. Here we
      hypothesize that a diet containing 70% protein from plants has similar efficacy
      and is tolerated by CKD patients. METHODS: Thirteen subjects with CKD 3-4
      received an omnivorous diet containing 70% protein from plants for 4 weeks. The
      primary outcome was change in 24 h urine phosphorus. Secondary outcomes were
      changes in serum phosphorus, FGF23, PTH, urine sodium excretion, grip strength
      and fat free mass. Repeated measures analysis of variance (ANOVA) was used to
      test differences in parameters over the 4 weeks. RESULTS: Mean age of subjects
      was 54.8 years. Median eGFR was 26 (IQR 14.7) ml/min/1.73 m(2). Over the 4-week
      period, urine phosphorus significantly decreased by 215 +/- 232 mg/day (p <
      0.001). No significant changes in serum FGF23, phosphorus or PTH were noted.
      Urine sodium and titratable acid decreased significantly on the diet. Hand grip
      strength and fat-free mass did not change. There were two hyperkalemia events
      both 5.8 mEq/l, corrected by food substitutions. No other adverse events were
      observed. CONCLUSIONS: A 70% plant protein diet is safe, tolerated, and
      efficacious in lowering urine phosphorus excretion and may be an alternative to
      phosphate binders.

PMID- 25613677
TI  - The cryptophycins as potent payloads for antibody drug conjugates.
AB  - The cryptophycins are a potent class of cytotoxic agents that were evaluated as
      antibody drug conjugate (ADC) payloads. Free cryptophycin analog 1 displayed cell
      activity an order of magnitude more potent than approved ADC payloads MMAE and
      DM1. This potency increase was also reflected in the activity of the cryptophycin
      ADCs, attached via a either cleavable or non-cleavable linker. 

PMID- 25613676
TI  - Discovery of diazepane amide DORAs and 2-SORAs enabled by exploration of
      isosteric quinazoline replacements.
AB  - Dual orexin receptor antagonists (DORAs), or orexin 1 (OX1) and orexin 2 (OX2)
      receptor antagonists, have demonstrated clinical utility for the treatment of
      insomnia. Medicinal chemistry efforts focused on the reduction of bioactivation
      potential of diazepane amide 1 through the modification of the Western
      heterocycle resulted in the discovery of suvorexant, a DORA recently approved by
      the FDA for the treatment of insomnia. A second strategy towards reducing
      bioactivation risk is presented herein through the exploration of monocyclic
      quinazoline isosteres, namely substituted pyrimidines. These studies afforded
      potent DORAs with significantly reduced bioactivation risk and efficacy in rodent
      sleep models. Surprisingly, side products from the chemistry used to produce
      these DORAs yielded isomeric pyrimidine-containing diazepane amides possessing
      selective OX2R antagonist (2-SORA) profiles. Additional exploration of these
      isomeric pyrimidines uncovered potent 2-SORA diazepane amides with sleep efficacy
      in mouse EEG studies. 

PMID- 25613678
TI  - 6-(Azaindol-2-yl)pyridine-3-sulfonamides as potent and selective inhibitors
      targeting hepatitis C virus NS4B.
AB  - A structure-activity relationship investigation of various 6-(azaindol-2
      yl)pyridine-3-sulfonamides using the HCV replicon cell culture assay led to the
      identification of a potent series of 7-azaindoles that target the hepatitis C
      virus NS4B. Compound 2ac, identified via further optimization of the series, has
      excellent potency against the HCV 1b replicon with an EC50 of 2nM and a
      selectivity index of >5000 with respect to cellular GAPDH RNA. Compound 2ac also
      has excellent oral plasma exposure levels in rats, dogs and monkeys and has a
      favorable liver to plasma distribution profile in rats. 

PMID- 25613679
TI  - Development of 2-aminooxazoline 3-azaxanthenes as orally efficacious beta
      secretase inhibitors for the potential treatment of Alzheimer's disease.
AB  - The beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is one of
      the most hotly pursued targets for the treatment of Alzheimer's disease. We used
      a structure- and property-based drug design approach to identify 2-aminooxazoline
      3-azaxanthenes as potent BACE1 inhibitors which significantly reduced CSF and
      brain Abeta levels in a rat pharmacodynamic model. Compared to the initial lead
      2, compound 28 exhibited reduced potential for QTc prolongation in a non-human
      primate cardiovascular safety model. 

PMID- 25613681
TI  - Determinants of first trimester combined test participation within the central
      region of the Netherlands.
AB  - OBJECTIVE: Our objective is to study the association between potentially
      influential determinants and first-trimester combined test (FCT) uptake rates in
      the central region of the Netherlands. METHODS: Data were extracted from the
      national prenatal screening database Peridos and the Netherlands Perinatal
      Registry and compared at the level of the health care provider. Univariable and
      multivariable linear regression analysis was used to determine the effect of
      determinants (maternal age, parity, socio-economic status (SES), mode of
      conception, ethnicity and urbanisation) on uptake. RESULTS: Prenatal screening
      data were available for 24 657 women and overall uptake rate was 25.7%. The
      strongest association with FCT uptake was found for advanced maternal age (beta
      2.2; 95% CI [1.7, 2.8]). Grand multiparity had a significantly negative
      association with FCT uptake (beta -4.3; 95% CI [-5.9, -2.7]). Positive
      associations were found for very high urbanisation (beta 0.3; 95% CI [0.1, 0.4])
      and high SES (beta 0.2; 95% CI [0.0, 0.3]). CONCLUSION: Advanced maternal age is
      strongly associated with participation in prenatal testing. The role of age
      related risk perception should be incorporated in future policy making to support
      women in informed and autonomous decision making. The negative association of
      grand multiparity and FCT might be religion based but requires further research.
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 25613682
TI  - Efficacy of high-resolution cone-beam CT in the evaluation of carotid
      atheromatous plaque.
AB  - INTRODUCTION: A major disadvantage of carotid artery stenting (CAS) is the high
      incidence of perioperative cerebral embolism. Cerebral embolism after CAS is
      associated with soft plaque. Currently, higher spatial resolution imaging can be
      obtained with cone-beam CT (CB-CT). The correlation between the degree of
      contrast enhancement of the vasa vasorum (VV) on CB-CT and the vulnerability of
      plaque in terms of risk factors for CAS was evaluated. METHODS: 18 patients who
      underwent CAS had high-resolution CB-CT to evaluate enhancement of the VV
      covering carotid plaque performed intraoperatively. The appearance of the surface
      of the carotid plaque was classified as either enhancing (VV-positive) or non
      enhancing (VV-negative). Carotid plaque vulnerability on black-blood MRI (BB-MRI)
      and postoperative ipsilateral ischemic lesions on diffusion-weighted imaging
      (DWI) were analyzed in the two groups. RESULTS: Of the 18 patients, 9 were VV
      positive and 9 were VV-negative. The proportion of ipsilateral new ischemic
      lesions on DWI was significantly higher in the VV-positive group than in the VV
      negative group (8/9 patients (88.9%) vs 3/9 patients (33.3%), p=0.026). BB-MRI
      was performed preoperatively in 15 of 18 patients. The proportion of unstable
      plaque on BB-MRI was significantly higher in the VV-positive group than in the VV
      negative group (9/9 patients (100%) vs 1/6 patients (16.7%), p=0.002).
      CONCLUSIONS: Enhancement of the VV covering carotid plaque on high-resolution CB
      CT was significantly associated with unstable plaque on BB-MRI and postoperative
      ipsilateral new ischemic lesions.

PMID- 25613683
TI  - Impact of epiphora on vision-related quality of life.
AB  - BACKGROUND: The study aimed to evaluate vision-related quality of life (QOL) in
      epiphora (excessive tear production) patients. METHODS: A total of 342 epiphora
      patients who visited ophthalmology clinics at 21 general hospitals during a 1
      week period were enrolled; 245 females and 97 males with a mean age of 52+/-13
      years. Participants completed a self-administered questionnaire on the extent to
      which epiphora limited their daily activities. Questions on frequency of
      discomfort with daily activities were answered on scale of a 0-4. Daily
      activities that were assessed included reading, daytime and nighttime driving,
      working at a computer, watching TV, work-related activities, household
      activities, outdoor activities, interpersonal relations, and general happiness. A
      correlation analysis was performed between the scores and patient ages. Scores
      were compared with the clinical factors of gender, bilaterality, and lacrimal
      irrigation pattern. Presurgical and postsurgical scores in a subset of epiphora
      patients who underwent surgery were compared. RESULTS: Outdoor activities were
      among those that epiphora most significantly hindered. Age had a negative
      correlation with interpersonal relations scores. Female patients tended to have
      more discomfort than males in conducting household activities, outdoor
      activities, and interpersonal relations. Bilaterality showed no differences in
      QOL. Patients with complete obstruction of lacrimal irrigation recorded higher
      scores in all daily activities than those with partial or no obstruction. For
      vision-related QOL, post-surgical scores were improved significantly compared
      with pre-surgical scores. CONCLUSION: Epiphora can affect a broad array of daily
      activities. Corrective measures for epiphora can improve vision-related QOL, and
      this may provide guidance for physicians in managing epiphora patients.

PMID- 25613684
TI  - A triple murder.
AB  - Three partially burnt bodies were found in a burnt out bedroom. A candle and
      matches were found on a partially burnt bed, suggesting accidental deaths.
      Careful scene analysis and forensic post-mortems demonstrated that this was a
      multiple murder rather than an accident. 

PMID- 25613685
TI  - Do the advantages of performing 500 operations annually justify the disruption
      associated with the potential closure of 3 centres in England?

PMID- 25613686
TI  - Synaptic modulation of excitatory synaptic transmission by nicotinic
      acetylcholine receptors in spinal ventral horn neurons.
AB  - Nicotinic acetylcholine receptors (nAChRs) are distributed widely in the central
      nervous system and play important roles in higher brain functions, including
      learning, memory, and recognition. However, functions of the cholinergic system
      in spinal motoneurons remain poorly understood. In this study, we investigated
      the actions of presynaptic and postsynaptic nAChRs in spinal ventral horn neurons
      by performing whole-cell patch-clamp recordings on lumbar slices from male rats.
      The application of nicotine or acetylcholine generated slow inward currents and
      increased the frequency and amplitude of spontaneous excitatory postsynaptic
      currents (sEPSCs). Slow inward currents by acetylcholine or nicotine were not
      inhibited by tetrodotoxin (TTX) or glutamate receptor antagonists. In the
      presence of TTX, the frequency and amplitude of miniature excitatory postsynaptic
      currents (mEPSCs) were also increased by acetylcholine or nicotine. A selective
      alpha4beta2 nicotinic receptor antagonist, dihydro-beta-erythroidine hydrobromide
      (DhbetaE), significantly decreased nicotine-induced inward currents without
      affecting the enhancement of sEPSCs and mEPSCs. In addition, a selective alpha7
      nicotinic receptor antagonist, methyllycaconitine, did not affect either nicotine
      induced inward currents or the enhancement of sEPSCs and mEPSCs. These results
      suggest that alpha4beta2 AChRs are localized at postsynaptic sites in the spinal
      ventral horn, non-alpha4beta2 and non-alpha7 nAChRs are located presynaptically,
      and nAChRs enhance excitatory synaptic transmission in the spinal ventral horn. 

PMID- 25613687
TI  - Melanin-concentrating hormone inputs to the nucleus accumbens originate from
      distinct hypothalamic sources and are apposed to GABAergic and cholinergic cells
      in the Long-Evans rat brain.
AB  - Melanin-concentrating hormone [MCH] is a neuropeptide that modulates several
      behaviors, such as feeding and reward. Because the hedonic and rewarding features
      of a food also influence feeding behavior, the nucleus accumbens [Acb] has been
      highlighted as a key area integrating these roles. Functional data confirm that
      MCH acts on a subdivision of the Acb; however, considering the importance of
      finding anatomical and neurochemical data that correlate the previously
      demonstrated function of MCH, we delineated this investigation based on the
      following points: (1) Is there a pattern of innervation by MCH fibers regarding
      the subregions within the Acb? (2) Specifically, which hypothalamic nuclei
      synthesize MCH and innervate the Acb? (3) Finally, what are the neurochemical
      identities of the accumbal neurons innervated by MCH inputs? We examined the MCH
      immunoreactivity [MCH-ir] in the Acb in rat brains using the peroxidase
      technique. Additionally, after injecting retrograde neuronal tracer [Fluoro
      Gold(r) - FG(r)] into subdivisions of the Acb [shell or core], we mapped single-
      or double-labeled cells. Moreover, using a double immunoperoxidase protocol, we
      investigated the MCH-ir fibers for gamma-aminobutyric acid [GABA]-ir and choline
      acetyltransferase [ChAT]-ir cells in the shell subdivision of the Acb [AcbSh]. We
      found that the MCH-ir fibers preferentially innervate the medial AcbSh,
      particularly the septal pole. This innervation originated from the incerto
      hypothalamic area [IHy], internuclear area, lateral hypothalamic area,
      perifornical area, periventricular nucleus and posterior hypothalamus. Moreover,
      the IHy has the highest relationship between double/single retrogradely labeled
      cells [n=5.33+/-0.66/16+/-0.93, i.e. 33.33%] in the whole hypothalamus.
      Furthermore, our data suggest that MCH-ir fibers are in apposition to GABAergic
      and cholinergic cells in the AcbSh. Therefore, we provide anatomical support to
      the ongoing functional studies investigating the relation among the hypothalamus,
      MCH transmission into the Acb and the involvement of known neuronal phenotypes
      within the AcbSh. 

PMID- 25613688
TI  - Oleuropein suppresses LPS-induced inflammatory responses in RAW 264.7 cell and
      zebrafish.
AB  - Oleuropein is one of the primary phenolic compounds present in olive leaf. In
      this study, the anti-inflammatory effect of oleuropein was investigated using
      lipopolysaccharide (LPS)-stimulated RAW 264.7 and a zebrafish model. The
      inhibitory effect of oleuropein on LPS-induced NO production in macrophages was
      supported by the suppression of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2). In addition, our enzyme immunoassay showed that
      oleuropein suppressed the release of pro-inflammatory cytokines such as
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Oleuropein inhibited the
      translocation of p65 by suppressing phosphorylation of inhibitory kappa B-alpha
      (IkappaB-alpha). Oleuropein also decreased activation of ERK1/2 and JNK, which
      are associated with LPS-induced inflammation, and its downstream gene of AP-1.
      Furthermore, oleuropein inhibited LPS-stimulated NO generation in a zebrafish
      model. Taken together, our results demonstrated that oleuropein could reduce
      inflammatory responses by inhibiting TLR and MAPK signaling, and may be used as
      an anti-inflammatory agent. 

PMID- 25613690
TI  - Subclonality and prenatal origin of RAS mutations in KMT2A (MLL)-rearranged
      infant acute lymphoblastic leukaemia.

PMID- 25613689
TI  - Survival and proliferation of the lysogenic bacteriophage CTXPhi in Vibrio
      cholerae.
AB  - The lysogenic phage CTXPhi of Vibrio cholerae can transfer the cholera toxin gene
      both horizontally (inter-strain) and vertically (cell proliferation). Due to its
      diversity in form and species, the complexity of regulatory mechanisms, and the
      important role of the infection mechanism in the production of new virulent
      strains of V. cholerae, the study of the lysogenic phage CTXPhi has attracted
      much attention. Based on the progress of current research, the genomic features
      and their arrangement, the host-dependent regulatory mechanisms of CTXPhi phage
      survival, proliferation and propagation were reviewed to further understand the
      phage's role in the evolutionary and epidemiological mechanisms of V. cholerae. 

PMID- 25613691
TI  - Measures of ventricles and evans' index: from neonate to adolescent.
AB  - Ventricle sizes are important for the early diagnosis of hydrocephalus or for
      follow-up after ventriculostomy. Diameters of ventricles may change, especially
      in childhood. This study aims to provide normative data about ventricle
      diameters. Among 14,854 cranial MRI performed between 2011 and 2013, 2,755 images
      of Turkish children aged 0-18 years were obtained. After exclusions, 517 images
      were left. Four radiologists were trained by a pediatric radiologist. Twenty
      images were assessed by all radiologists for a pilot study to see that there was
      no interobserver variation. There were 10-22 children in each age group. The
      maximum width of the third ventricle was 5.54 +/- 1.29 mm in males in age group 1
      and 4.98 +/- 1.08 mm in females in age group 2. The Evans' index was <0.3 and
      consistent with the literature. The third ventricle/basilar artery width ratio
      was found to be >1 and <2 in all age groups and both gender groups. Our study
      showed the ventricle size data of children in various age groups from newborn to
      adolescent. The ventricle volume/cerebral parenchyma ratio seems to decrease with
      age. We think that these data can be applied in clinical practice, especially for
      the early diagnosis of hydrocephalus.

PMID- 25613692
TI  - Synthesis of silver nanoparticles using Solanum trilobatum fruits extract and its
      antibacterial, cytotoxic activity against human breast cancer cell line MCF 7.
AB  - In the present study, we have synthesized silver nanoparticles by a simple and
      eco-friendly method using unripe fruits of Solanum trilobatum. The aqueous silver
      ions when exposed to unripe fruits extract were reduced and stabilized over long
      time resulting in biosynthesis of surface functionalized silver nanoparticles.
      The bio-reduced silver nanoparticles were characterized by UV-visible
      spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive
      spectroscopy (EDX) and X-ray diffraction (XRD). These biologically synthesized
      silver nanoparticles were tested for its antibacterial activity against few human
      pathogenic bacteria including Gram-positive (Streptococcus mutans, Enterococcus
      faecalis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria.
      In addition, we also demonstrated anticancer activity of these nanoparticles in
      vitro against human breast cancer cell line (MCF 7) using MTT, nuclear morphology
      assay, Western blot and RT-PCR expression. These results taken together show the
      potential applications of biosynthesized silver nanoparticles using S. trilobatum
      fruits. 

PMID- 25613693
TI  - Synthesis, characterization, single crystal X-ray determination, fluorescence and
      electrochemical studies of new dinuclear nickel(II) and oxovanadium(IV) complexes
      containing double Schiff base ligands.
AB  - A series of new bimetallic complexes of nickel(II) and vanadium(IV) have been
      synthesized by the reaction of the new double bidentate Schiff base ligands with
      nickel acetate and vanadyl acetylacetonate in 1:1 M ratio. In nickel and also
      vanadyl complexes the ligands were coordinated to the metals via the imine N and
      enolic O atoms. The complexes have been found to possess 1:1 metals to ligands
      stoichiometry and the molar conductance data revealed that the metal complexes
      were non-electrolytes. The nickel and vanadyl complexes exhibited distorted
      square planar and square pyramidal coordination geometries, respectively. The
      emission spectra of the ligands and their complexes were studied in methanol.
      Electrochemical properties of the ligands and their metal complexes were also
      investigated in DMSO solvent at 150 mV s(-1) scan rate. The ligands and metal
      complexes showed both quasi-reversible and irreversible processes at this scan
      rate. The Schiff bases and their complexes have been characterized by FT-IR, 1H
      NMR, UV/Vis spectroscopies, elemental analysis and conductometry. The crystal
      structure of the nickel complex has been determined by single crystal X-ray
      diffraction.

PMID- 25613694
TI  - Compatible validated spectrofluorimetric and spectrophotometric methods for
      determination of vildagliptin and saxagliptin by factorial design experiments.
AB  - Simple, selective and reproducible spectrofluorimetric and spectrophotometric
      methods have been developed for the determination of vildagliptin and saxagliptin
      in bulk and their pharmaceutical dosage forms. The first proposed
      spectrofluorimetric method is based on the dansylation reaction of the amino
      group of vildagliptin with dansyl chloride to form a highly fluorescent product.
      The formed product was measured spectrofluorimetrically at 455 nm after
      excitation at 345 nm. Beer's law was obeyed in a concentration range of 100-600
      MUg ml(-1). The second proposed spectrophotometric method is based on the charge
      transfer complex of saxagliptin with tetrachloro-1,4-benzoquinone (p-chloranil).
      The formed charge transfer complex was measured spectrophotometrically at 530 nm.
      Beer's law was obeyed in a concentration range of 100-850 MUg ml(-1). The third
      proposed spectrophotometric method is based on the condensation reaction of the
      primary amino group of saxagliptin with formaldehyde and acetyl acetone to form a
      yellow colored product known as Hantzsch reaction, measured at 342.5 nm. Beer's
      law was obeyed in a concentration range of 50-300 MUg ml(-1). All the variables
      were studied to optimize the reactions' conditions using factorial design. The
      developed methods were validated and proved to be specific and accurate for
      quality control of vildagliptin and saxagliptin in their pharmaceutical dosage
      forms.

PMID- 25613695
TI  - Switching of emission of a styryl dye in cucurbit[7]uril: a comprehensive
      experimental and theoretical study.
AB  - Intriguing colour change and change in fluorescence band of 2-(4
      (dimethylamino)styryl)-1-methylpyridinium iodide from nonpolar to polar protic
      solvent, and also from molecular container cucurbit[7]uril environment to polar
      protic solvent has been reported here. This interesting colour change of this dye
      with respect to the medium makes this dye useful as a sensor. Change in spectral
      characteristics of DASPMI along with change of colour from orange to yellow with
      increasing polarity of medium is interpreted as due to negative
      solvatochromatism. Complexations of probe-cucurbit[7]uril (1:1 and 2:1) cause
      structural change of the probe molecule due to hydrogen bond interaction of
      cationic part of the dye with CO group of cucurbit[7]uril and the colour change
      of the solution ensued. On addition of sodium chloride to the inclusion complex
      the dye is released from cucurbit[7]uril interior with colour of the solution
      reverted back. Theoretical results show that one carbon atom in the styryl part
      containing the positive charge gets too close to a carbon atom of cucurbit[7]uril
      to cause a phenomenal increase of dipole moment by 10X. 

PMID- 25613696
TI  - Urban-rural differences in Roman Dorset, England: A bioarchaeological perspective
      on Roman settlements.
AB  - In the Roman period, urban and rural ways of living were differentiated
      philosophically and legally, and this is the first regional study of these
      contrasting life-ways. Focusing on frailty and mortality risk, we investigated
      how these differed by age, sex, and status, using coffin type as a proxy for
      social status. We employed skeletal data from 344 individuals: 150 rural and 194
      urban (1st-5th centuries A.D.) from Dorset, England. Frailty and mortality risk
      were examined using indicators of stress (cribra orbitalia, porotic hyperostosis,
      nonspecific periostitis, and enamel hypoplastic defects), specific metabolic and
      infectious diseases (rickets, scurvy, and tuberculosis), and dental health
      (carious lesions and calculus). These variables were studied using Chi-square,
      Siler model of mortality, Kaplan-Meier analysis, and the Gompertz model of adult
      mortality. Our study found that overall, mortality risk and survivorship did not
      differ between cemetery types but when the data were examined by age, mortality
      risk was only significantly higher for urban subadults. Demographic differences
      were found, with urban cemeteries having more 0-10 and >35 year olds, and for
      health, urban cemeteries had significantly higher frequencies of enamel
      hypoplastic defects, carious lesions, and rickets. Interestingly, no significant
      difference in status was observed between rural and urban cemeteries. The most
      significant finding was the influence of the skeletal and funerary data from the
      Poundbury sites, which had different demographic profiles, significantly higher
      frequencies of the indicators of stress and dental health variables. In
      conclusion, there are significant health, demographic, and mortality differences
      between rural and urban populations in Roman Britain.

PMID- 25613697
TI  - WITHDRAWN: Production of a novel UBE2S anti-body and significance of its
      expression in some tumors.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25613680
TI  - Population-based multicase-control study in common tumors in Spain (MCC-Spain):
      rationale and study design.
AB  - INTRODUCTION: We present the protocol of a large population-based case-control
      study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental
      exposures and genetic factors. METHODS: Between 2008-2013, 10,106 subjects aged
      20-85 were enrolled in 23 hospitals and primary care centres in 12 Spanish
      provinces including 1,112 cases with a new diagnosis of prostate cancer, 1,738 of
      breast cancer, 2,140 of colorectal cancer, 459 of gastro-oesophageal cancer, 559
      cases with chronic lymphocytic leukaemia and 4,098 population controls frequency
      matched to cases by age, sex and region of residence. Participation rates ranged
      from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls.
      Participants completed a face-to-face computerized interview on sociodemographic
      factors, environmental exposures, occupation, medication, lifestyle, and personal
      and family medical history. In addition, participants completed a self
      administered food-frequency questionnaire and telephone interviews. Blood samples
      were collected from 76% of participants while saliva samples were collected in
      CLL cases and participants refusing blood extractions. Clinical information was
      recorded for cases and paraffin blocks and/or fresh tumor samples are available
      in most collaborating hospitals. Genotyping was done through an exome array
      enriched with genetic markers in specific pathways. Multiple analyses are planned
      to assess the association of environmental, personal and genetic risk factors for
      each tumor and to identify pleiotropic effects. DISCUSSION: This study, conducted
      within the Spanish Consortium for Biomedical Research in Epidemiology & Public
      Health (CIBERESP), is a unique initiative to evaluate etiological factors for
      common cancers and will promote cancer research and prevention in Spain.

PMID- 25613698
TI  - Epistatic interaction between adiponectin and survivin gene polymorphisms in
      endometrial carcinoma.
AB  - Adiponectin appears to play an important role in the development and progression
      of several obesity-related malignancies. Also, overexpression of survivin, an
      inhibitor of apoptosis protein, is associated with increased risk of cancers. The
      aim of this study was to investigate the association between two polymorphisms in
      the adiponectin gene and endometrial cancer (EC) risk. We also investigated
      whether epistasis between surviving and adiponectin gene polymorphisms are
      associated with EC risk in an Iranian population. The samples comprised formalin
      fixed, paraffin-embedded tissue sections obtained from the archive of the
      pathology department, Imam-Khomeini Hospital and Firouzgar hospital. After DNA
      extraction the genotyping was performed using PCR-RFLP technique. Single
      nucleotide polymorphisms (SNPs) in adiponectin (rs1063539, rs2241766) and
      survivin (rs9904341) gene were evaluated in the study. The increased frequency of
      ADIPOQ rs1063539C allele (CC+CG genotype) was associated with decreased EC risk
      [OR: 0.39(0.17-0.90)]. Survivin rs9904341C allele (CC+CG genotype) was associated
      with increased EC risk [crude OR: 2.75(1.27-5.95), adjusted OR: 2.93(1.27-6.76)].
      We observed an epistatic interaction between survivin rs9904341 CC+CG genotype
      and ADIPOQ rs1063539 GG genotype increasing the risk of EC compared to those with
      other genotypes [OR: 4.86(1.88-12.54), P=0.001]. Our findings indicate that
      adiponectin might have a modulatory effect on survivin role and function in EC,
      which requires further investigation. 

PMID- 25613699
TI  - PTEN and hTERT gene expression and the correlation with human hepatocellular
      carcinoma.
AB  - The aim of this study was to investigate the correlation between tumor suppressor
      gene phosphatase and tensin homolog (PTEN) expression levels and telomerase
      activity that mainly depends on telomerase reverse transcriptase (hTERT) in
      hepatocellular carcinoma (HCC) and paracancerous tissues. Immunohistochemistry
      and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to detect
      the expression of PTEN and hTERT in 58 cases with HCC and the corresponding
      paracancerous tissues. The correlation between PTEN and hTERT was analyzed. The
      PTEN mRNA and protein expression was significantly lower in HCC, as compared with
      the paracancerous tissues (P<0.01), while those of hTERT demonstrated the
      opposite expression pattern (P<0.01). Additionally, both the PTEN and hTERT
      protein and mRNA levels demonstrated a significantly negative correlation with
      one another (P<0.05). In conclusion, PTEN and hTERT have different roles in the
      development of HCC. A significantly negative correlation between PTEN and hTERT
      gene expression indicates that hTERT activation and upregulation may be conferred
      by the loss of PTEN gene expression in HCC. The combined detection of PTEN and
      hTERT may provide critical clinical evidence for the diagnosis and biological
      behavior of HCC. 

PMID- 25613700
TI  - Prognostic indicators of social outcomes in persons who sustained an injury in a
      road traffic crash.
AB  - INTRODUCTION: There is a lack of longitudinal studies with adequate sample size
      and follow-up period which have objectively assessed social outcomes among those
      with mild or moderate musculoskeletal injury or that are not limited to hospital
      inpatients. We aimed to address this gap by prospectively assessing the potential
      predictors of return to pre-injury work and daily activities. METHODS: Persons
      with mild/moderate musculoskeletal injuries from a vehicle-related crash were
      surveyed within the first 3 months after the crash (baseline; n=364), and at 12
      (n=284) and 24 months (n=252). Participants self-reported return to work, and
      whether it was return to full or modified duties at work. Analyses were
      restricted to 170 participants who reported being in pre-injury paid work and had
      provided information at either 12 months only or at both 12 and 24 months. Return
      to usual activities was assessed using the European Quality of Life-5 Dimensions
      (EQ-5D) scale 'Usual Activities' dimension. RESULTS: Twenty-four months after
      injury 82% (n=121) had returned to work. After multivariable adjustment, not
      being admitted to hospital was associated with 44% higher likelihood of returning
      to work at 24 months. Not having any pre-injury chronic illness was associated
      with returning to work after 24 months, multivariable-adjusted risk ratio (RR),
      1.21 (95% confidence intervals, CI: 1.02-1.45). Each 1-SD increase in Medical
      Outcomes Survey Short Form-12 Mental Component Summary (SF-12 MCS) score at
      baseline was associated with returning to work at 24 months RR 1.13 (95% CI: 1.02
      1.25). Younger age, higher SF-12 physical component summary (PCS), and EQ-5D
      visual analogue scale (VAS) scores were mutually independent predictors of
      returning to usual activities 24 months later. CONCLUSION: A range of bio
      psychosocial factors, particularly quality of life measures, independently
      predicted social outcomes including return to work and return to usual daily
      activities. These determinants could be measured early in the recovery process
      and be potentially amenable to intervention.

PMID- 25613701
TI  - Associations with legal representation in a compensation setting 12 months after
      injury.
AB  - CONTEXT: Many people with Whiplash Associated Disorder (WAD) seek treatment
      though a compensation system where factors such as legal involvement have been
      reported as having a negative impact on recovery outcomes. OBJECTIVE: To compare
      those with and without legal involvement in their compensation claim, and
      identify associations with legal involvement at 12 months post injury; and longer
      term disability. STUDY DESIGN: Inception cohort study. PARTICIPANTS: 246 people
      with WAD compensation claim. OUTCOME MEASURES: Legal involvement and Functional
      Rating Index at 12 months post injury. METHODS: Participants were recruited from
      an insurance database. Baseline health (Functional Rating Index, Pain
      Catastrophising Scale and SF-36), socio-economic, work capacity, and claims data
      were collected within three months of injury and 12 months. Logistic regression
      models were used to identify associations with legal involvement at 12 months;
      and disability (FRI) at 12 months. RESULTS: At baseline 246 participants were
      enrolled into the study in a median 72 days post injury. At 12 months post injury
      52 (25%) had engaged a lawyer. The significant independent associations with
      legal involvement at 12 months were higher levels of initial disability, work
      disability, speaking a language other than English at home and lower levels of
      mental health. Specifically, the odds of lawyer involvement at 12 months post
      injury was 4.9 times greater for those with work disability; 2.3 times greater
      for those who spoke a language other than English at home. In terms of health,
      they had poorer mental health and for every 10 unit increase in the baseline FRI
      score the odds of having lawyer involvement increased by 38%. DISABILITY: at 12
      months (FRI) was significantly independently associated with, PCS-helplessness
      (p<0.001), age (p<0.001) and prior claim (p=0.001). CONCLUSION: This study
      suggests the people with lawyer involvement in their claim 12 months after injury
      have socio-economic disadvantage, have had a prior claim and a worse baseline
      health profile compared to those without a lawyer. Understanding this profile
      could allow for improved claims processes and targeted interventions to assist
      this group through any perceived complexities in the system and address the
      underlying reasons for lawyer participation within compensation schemes.

PMID- 25613702
TI  - WT1 deletion leading to severe 46,XY gonadal dysgenesis, Wilms tumor and
      gonadoblastoma: case report.
AB  - BACKGROUND: Heterozygous missense mutations in the WT1 gene that affect the
      function of the wild-type allele have been identified in Denys-Drash syndrome,
      which is characterized by severe gonadal dysgenesis, early-onset nephropathy and
      a predisposition to renal and gonadal cancer. Intron 9 splice-site mutations that
      influence the balance between WT1 isoforms cause a nearly similar phenotype,
      known as Frasier syndrome. Nonsense mutations and deletions only lead to WT1
      haploinsufficiency and, hence, to less severe gonadal dysgenesis and late-onset
      nephropathy. WT1 analysis is mandatory in 46,XY gonadal dysgenesis with renal
      abnormality. PATIENT: We describe a newborn with 46,XY severe partial gonadal
      dysgenesis, in whom structural renal anomalies and proteinuria were excluded.
      Gonadectomy was performed at the age of 1 month and the microscopy was thought to
      be suggestive for a gonadoblastoma. At the age of 9 months, the patient presented
      with a bilateral Wilms tumor. RESULTS: We found a heterozygous WT1 whole-gene
      deletion but no other gene defects. CONCLUSIONS: This case description
      illustrates that a WT1 deletion might be associated with a more severe phenotype
      than previously thought. It also illustrates that, even in the absence of renal
      abnormality, it is recommended to test promptly for WT1 defects in 46,XY gonadal
      dysgenesis.

PMID- 25613703
TI  - Discussion of emotional processing in a ten-session general (good) psychiatric
      treatment for borderline personality disorder.

PMID- 25613704
TI  - Introducing editorial changes.

PMID- 25613710
TI  - Thermal transport: Cool electronics.

PMID- 25613712
TI  - Material witness: Holding Rome together.

PMID- 25613711
TI  - Ferroelectrics: Negative capacitance detected.

PMID- 25613714
TI  - A systematic study of the effect of molecular weights of polyvinyl alcohol on
      polyvinyl alcohol-graphene oxide composite hydrogels.
AB  - Polyvinyl alcohol (PVA) hydrogels have been proposed for use as promising
      biomaterials in biomedical and tissue engineering, and graphene oxide (GO) has
      been recognized as a unique two-dimensional building block for various graphene
      based supramolecular architectures. In this article, we systematically studied
      the influence of three kinds of PVA with different molecular weights on the
      interaction between PVA and GO. Moreover, the effects of PVA on the gelation of
      GO were also investigated. The native PVA hydrogel, as well as PVA-GO hybrid
      hydrogels, have been thoroughly characterized by the phase behavior study and
      various techniques including field emission scanning electron microscopy (FE
      SEM), Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis
      (TGA) and rheological measurements. It can be seen that with the increase of the
      molecular weight of PVA, the addition of GO can effectively promote the gelation
      of PVA which can be reflected by a decrease of the critical gel concentration
      (CGC) for PVA-GO hydrogels. Dye adsorption experiments indicate that the toxic
      dye, i.e., methylene blue (MB), was efficiently entrapped in the PVA-GO xerogels.
      It is also demonstrated that the gelation of PVA and GO composites can be
      promoted by different supramolecular interactions, including hydrogen bonding and
      electrostatic interaction. This work indicates that the PVA-GO composite is a
      good candidate for preparing "super" and "smart" hydrogels and will enable
      further studies on the supramolecular chemistry of PVA, graphene and its
      derivatives. 

PMID- 25613713
TI  - Lipopolysaccharide binding protein, interleukin-10, interleukin-6 and C-reactive
      protein blood levels in acute ischemic stroke patients with post-stroke
      infection.
AB  - BACKGROUND: Ischemic stroke patients are prone to infection by stroke-induced
      immunodepression. We hypothesized that levels of lipopolysaccharide binding
      protein (LBP), interleukin-10 (IL-10), IL-6 and C-reactive protein (CRP) are
      early predictors for the development of stroke-associated infection. METHODS:
      Fifty-six patients with ischemic stroke (n = 51) and transient ischemic attack
      (TIA) (n = 5) who presented within 6 hours after symptom onset and who were free
      of detectable infection on admission were included in the study. Of these, 20
      developed early infections during the first week. Blood samples were taken at 6,
      12, and 24 hours and at 3 and 7 days after stroke onset. Levels of LBP, Il-10, IL
      6 and CRP, as well as S100B, were measured as markers of inflammation and brain
      damage by commercially available immunometric tests. RESULTS: In the univariate
      analysis, levels of LBP, IL-10, IL-6 and CRP significantly differed between
      patients who developed an infection and those who did not. In the binary logistic
      regression analysis, which was adjusted for National Institutes of Health Stroke
      Scale (NIHSS) on admission, stroke subtype and S100B peak levels, as indicator of
      the extent of brain damage, IL-10 at 6 hours, CRP at 6 hours and NIHSS on
      admission were identified as independent predictors of infection (IL-10: P =
      0.009; CRP: P = 0.018; NIHSS: P = 0.041). The area under the curve (AUC) of the
      receiver operating characteristic (ROC) curves in relation to the dichotomized
      status of the infection (infection versus no infection) was 0.74 (95% confidence
      interval: 0.59 to 0.88) for CRP at 6 hours, 0.76 (0.61 to 0.9) for IL-10 at 6
      hours, 0.83 (0.71 to 0.94) for NIHSS on admission and 0.94 (0.88 to 1) for the
      combination of CRP, IL-10 and NIHSS. In a subanalysis, 16 patients with early
      infections were matched with 16 patients without infection according to S100B
      peak levels. Here, the temporal pattern of LBP, IL-10, IL-6 and CRP significantly
      differed between the patient groups. CONCLUSIONS: Our data show that blood levels
      of inflammation markers may be used as early predictors of stroke-associated
      infection. We propose prospective studies to investigate if the calculated cut
      offs of CRP, IL-10 and NIHSS might help to identify patients who should receive
      early preventive antibiotic treatment.

PMID- 25613715
TI  - Oxygenated metabolism of PUFA: Analysis and biological relevance.

PMID- 25613716
TI  - Decennial administration in young adults of a reduced-antigen content diphtheria,
      tetanus, acellular pertussis vaccine containing two different concentrations of
      aluminium.
AB  - BACKGROUND: Regular booster vaccination might be necessary throughout life to
      protect against pertussis infection. Nevertheless the duration of protection
      after booster vaccination remains unclear. In this study, antibody persistence up
      to 10 years after previous vaccination of adolescents (N=478) with combined
      reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (dTpa,
      BoostrixTM, GlaxoSmithKline Belgium) containing 0.5mg, 0.3mg or 0.133mg of
      aluminium was assessed. The immunogenicity, reactogenicity and safety of a
      decennial booster dTpa dose were also investigated. METHODS: Young adults
      vaccinated as adolescents in the initial booster study were invited to
      participate in an assessment of antibody persistence at years 8.5 and 10, and to
      receive a dTpa booster dose at year 10 with immunogenicity assessment one month
      later. Those who originally received the 0.5mg or 0.3mg formulations received the
      same vaccine at year 10. Those in the 0.133mg group received the 0.5mg
      formulation. Reactogenicity and safety endpoints were captured until 30 days
      after booster vaccination. RESULTS: Prior to the decennial booster at year 8.5
      and year 10, all participants had seroprotective antibodies for diphtheria (ELISA
      or neutralisation assay) and tetanus. At least 77.8% were seropositive for anti
      pertussis toxin (PT) antibodies at year 8.5 and 82.8% at year 10. All
      participants were seropositive for antibodies for filamentous haemagglutinin and
      pertactin at both time points. The decennial booster dose induced robust
      increases in antibody GMCs to all antigens. The post-booster anti-PT geometric
      mean concentration was 82.5EL.U/ml (95%CI 67.0-101.6) and 124.0 (103.5-148.5) in
      the 0.3mg and 0.5mg groups, respectively. The reactogenicity and safety profile
      of the decennial booster dose was consistent with the known safety profile of
      dTpa. No serious adverse events were reported. CONCLUSIONS: Decennial booster
      vaccination with either of the two licensed formulations of dTpa was highly
      immunogenic and well tolerated in young adults. Either formulation could be
      confidently used as a decennial booster. This study is registered at
      www.clinicaltrials.govNCT01147900.

PMID- 25613717
TI  - Early impact of PCV7/PCV13 sequential introduction to the national pediatric
      immunization plan, on adult invasive pneumococcal disease: A nationwide
      surveillance study.
AB  - BACKGROUND: PCV7 was introduced as a universal childhood vaccination in Israel on
      July 2009 and was gradually replaced by PCV13 from November 2010. We report data
      on adult invasive pneumococcal disease (IPD), two years post PCV13
      implementation. METHODS: An ongoing nationwide active surveillance (all 27
      laboratories performing blood/CSF cultures nationwide), initiated in 2009,
      providing all blood/CSF Streptococcus pneumoniae isolated from persons >=18
      years. Capture-recapture method assured reporting of >95% cases. All isolates
      were serotyped in one central laboratory. Medical history and outcomes were
      recorded in ~90%. RESULTS: Of 1809 IPD episodes, S. pneumoniae was isolated from
      the blood in 95% and most cases had pneumonia. Predisposing comorbidities were
      present in >70%. During the four study years, overall IPD incidence decreased
      from 9.2 to 7.2/100,000, incidence of pneumonia and particularly severe pneumonia
      cases decreased significantly from 6.6 to 4.7/100,000, (p=0.029). Vaccine type
      (VT7/VT13) serotypes decreased by 70%/57% within 4 years. This was accompanied by
      a 52% increase in non-VT13 strains. These changes were most apparent in winter.
      PCV impact was most pronounced in younger adults (39% decrease in overall IPD
      with only a non-significant increase in non-VT13 cases) while in those >65 years
      a non-significant decrease in overall IPD was observed with a 64% increase in non
      VT13 cases. Non-VT13 serotypes that increased significantly were 12F, 15A 10A and
      6C. A continuous reduction in isolates with penicillin MIC>0.06MUg/ml was
      observed (26% to 11%, p<0.001). CONCLUSIONS: Four years after PCV7 and 2.5 years
      after PCV13 universal implementation in children, incidence of adult IPD caused
      by VT7 and VT13 decreased in all ages, mainly in younger adults. Despite increase
      in non-VT13 IPD, overall IPD decreased. Additional follow-up is needed to
      determine the long-term impact of PCV13.

PMID- 25613718
TI  - Neutralising antibody response in domestic cats immunised with a commercial
      feline immunodeficiency virus (FIV) vaccine.
AB  - Across human and veterinary medicine, vaccines against only two retroviral
      infections have been brought to market successfully, the vaccines against feline
      leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). FeLV vaccines
      have been a global success story, reducing virus prevalence in countries where
      uptake is high. In contrast, the more recent FIV vaccine was introduced in 2002
      and the degree of protection afforded in the field remains to be established.
      However, given the similarities between FIV and HIV, field studies of FIV vaccine
      efficacy are likely to advise and inform the development of future approaches to
      HIV vaccination. Here we assessed the neutralising antibody response induced by
      FIV vaccination against a panel of FIV isolates, by testing blood samples
      collected from client-owned vaccinated Australian cats. We examined the molecular
      and phenotypic properties of 24 envs isolated from one vaccinated cat that we
      speculated might have become infected following natural exposure to FIV. Cats
      vaccinated against FIV did not display broadly neutralising antibodies,
      suggesting that protection may not extend to some virulent recombinant strains of
      FIV circulating in Australia. 

PMID- 25613719
TI  - The adjuvant effect of low frequency ultrasound when applied with an inactivated
      Aeromonas salmonicida vaccine to rainbow trout (Oncorhynchus mykiss).
AB  - Vaccine adjuvants are classified according to their properties of either inducing
      the persistence of antigens within the animal after immunisation and/or
      activation of the animal's immune response. The adjuvant effect of low intensity
      low frequency sonophoresis (LFS) was tested in rainbow trout using an Aeromonas
      salmonicida bacterin vaccine administered by immersion vaccination using LFS at
      37 kHz. The adjuvant effect obtained with LFS was compared with that of normal
      immersion or intraperitoneal injection vaccination. Quantitative PCR was used to
      measure bacterial DNA in vaccinated fish up to 35 days post-vaccination, while RT
      qPCR was used to assess gene expression during the early and late immune response
      post-vaccination. Results showed that antigen uptake in the gills was
      significantly higher in the group exposed to low intensity LFS compared to the
      other two vaccination groups 15 min post-vaccination, but this initially high
      uptake did not persist over the rest of the experiment. In the kidney, by
      comparison, the vast majority of the samples analysed did not show the presence
      or persistence of the bacterin. Showing that the route of vaccine uptake using
      the A. salmonicida bacterin, does not influence the persistence of the bacterin
      in the gills or the kidney. On the other hand, LFS induced a higher inflammatory
      response and T-helper cell activation, characterized by a significant up
      regulation of interleukin-8 (IL-8), IL-1beta and CD-4, respectively. The
      expression of Ig-M, Ig-T and Ig-D was up-regulated in gills (being significant
      for Ig-M), but not in the spleen and kidney of the sonicated group. Conversely,
      Ig-M was up-regulated in the spleen of the non-sonicated groups, but not in the
      sonicated group. This highlights the ability of ultrasound to enhance mucosal
      immunity. It remains to be established whether the up-regulation of Ig-M in gills
      would be sufficient to offer protection in fish infected with A. salmonicida.

PMID- 25613720
TI  - Whole inactivated avian Influenza H9N2 viruses induce nasal submucosal dendritic
      cells to sample luminal viruses via transepithelial dendrites and trigger
      subsequent DC maturation.
AB  - Nasal mucosal barrier is a key impediment for the absorption of influenza whole
      inactivated virus (WIV) intranasal vaccine. Yet it is still unclear how WIV cross
      the epithelial cells (ECs) in nasal cavity. Here, in vitro, a coculture system
      was well established, consisting of surrogate nasal ECs (Calu-3) and dendritic
      cells (DCs). After adding H9N2 WIV on the apical side of ECs, we found that
      submucosal DCs extended their transepithelial dendrites (TEDs) and sampled
      luminal viruses. However, ECs were not involved in the transepithelial transport
      of viruses. Subsequently, the phenotypic and functional maturation of DCs were
      also enhanced, whereas they were attenuated after blocking of TED formation by
      anti-JAM1 antibody. In vivo, we confirmed that H9N2 WIV were capable of inducing
      nasal submucosal DCs to sample luminal viruses via TEDs in the nasal passage but
      not nasal-associated lymphoid tissue (NALT). CD103(+) and CD103(-) DC subsets
      participated in this process. Of note, chemokine CCL20, released from the H9N2
      WIV-induced ECs, played a vital role in DC recruitment and TED formation. Taken
      together, our findings indicated that TEDs played a critical role in facilitating
      viral transport across the epithelial barrier, which may guide the design of
      novel nasal mucosal vaccine strategies. 

PMID- 25613721
TI  - Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in
      adults.
AB  - BACKGROUND: An intradermal (ID) trivalent split-virion influenza vaccine (IIV3
      ID) (Fluzone((r)) Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available
      in the US since the 2011/2012 influenza season for adults aged 18-64 years. This
      study examined whether adding a second B-lineage strain affects immunogenicity
      and safety. METHODS: This randomized, double-blind, multicentre trial evaluated
      the immunogenicity and safety of an intradermal quadrivalent split-virion
      influenza vaccine (IIV4-ID) in adults 18-64 years of age in the US during the
      2012-2013 influenza season. Participants were randomized 2:1:1 to receive a
      single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID
      containing the alternate B-lineage strain. Haemagglutination inhibition antibody
      titres were assessed in two-thirds of participants before vaccination and 28 days
      after vaccination. RESULTS: 1672 participants were vaccinated with IIV4-ID, 837
      with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four
      vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to
      the response to the IIV3-ID vaccines containing the matched strains. For both B
      strains, post-vaccination antibody responses to IIV4-ID were statistically
      superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse
      events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited
      reactions were pain, pruritus, myalgia, headache, and malaise; and most were
      grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was
      statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions
      of participants with at least one grade 2 or 3 systemic reaction. CONCLUSIONS:
      Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and
      matched B strains and superior for the unmatched B strains. IIV4-ID was well
      tolerated without any safety concerns. IIV4-ID may help address an unmet need due
      to mismatched B strains in previous influenza vaccines.

PMID- 25613722
TI  - Determinants of influenza vaccination among young Taiwanese children.
AB  - OBJECTIVE: According to the Health Belief Model (HBM), individual perceptions of
      susceptibility, severity, benefit, barrier, self-efficacy, and cues to action are
      associated with health actions. In this study, we investigated the perceptions
      and social factors that influence the intention to vaccinate children against
      influenza among parents of young Taiwanese children. METHODS: A nationwide survey
      was performed using stratified random sampling to explore the beliefs, attitudes,
      and intentions of parents/main caregivers with regard to vaccinating children
      aged 6 months to 3 years against influenza. A questionnaire was developed based
      on the HBM and multivariate logistic regression analyses of 1300 eligible
      participants were used to identify significant predictors of the intention to
      vaccinate. RESULTS: Greater perceived benefit, cues to action, and self-efficacy
      of childhood vaccination against influenza were positively associated with the
      intention to vaccinate. Children's experience of influenza vaccinations in the
      past year was also a positive predictor. However, perceived susceptibility,
      perceived severity regarding influenza and perceived barriers to vaccination were
      not predictive of the intention to vaccinate. CONCLUSION: In addition to
      perceived benefits and cues to action, self-efficacy of parents/main caregivers
      was significantly predictive of their intention to accept influenza vaccination
      for their young children. These components of the HBM could be used in
      formulating strategies aimed at promoting the use of influenza vaccine.

PMID- 25613723
TI  - Vaccine protection of chickens against antigenically diverse H5 highly pathogenic
      avian influenza isolates with a live HVT vector vaccine expressing the influenza
      hemagglutinin gene derived from a clade 2.2 avian influenza virus.
AB  - Vaccination is an important tool in the protection of poultry against avian
      influenza (AI). For field use, the overwhelming majority of AI vaccines produced
      are inactivated whole virus formulated into an oil emulsion. However, recombinant
      vectored vaccines are gaining use for their ability to induce protection against
      heterologous isolates and ability to overcome maternal antibody interference. In
      these studies, we compared protection of chickens provided by a turkey
      herpesvirus (HVT) vector vaccine expressing the hemagglutinin (HA) gene from a
      clade 2.2 H5N1 strain (A/swan/Hungary/4999/2006) against homologous H5N1 as well
      as heterologous H5N1 and H5N2 highly pathogenic (HP) AI challenge. The results
      demonstrated all vaccinated birds were protected from clinical signs of disease
      and mortality following homologous challenge. In addition, oral and cloacal swabs
      taken from challenged birds demonstrated that vaccinated birds had lower
      incidence and titers of viral shedding compared to sham-vaccinated birds.
      Following heterologous H5N1 or H5N2 HPAI challenge, 80-95% of birds receiving the
      HVT vector AI vaccine at day of age survived challenge with fewer birds shedding
      virus after challenge than sham vaccinated birds. In vitro cytotoxicity analysis
      demonstrated that splenic T lymphocytes from HVT-vector-AI vaccinated chickens
      recognized MHC-matched target cells infected with H5, as well as H6, H7, or H9 AI
      virus. Taken together, these studies provide support for the use of HVT vector
      vaccines expressing HA to protect poultry against multiple lineages of HPAI, and
      that both humoral and cellular immunity induced by live vaccines likely
      contributes to protection. 

PMID- 25613724
TI  - Rapid analysis of Achillea tenuifolia Lam essential oils by
      polythiophene/hexagonally ordered silica nanocomposite coating as a solid-phase
      microextraction fibre.
AB  - In this work, a highly porous fibre coated with polythiophene/hexagonally ordered
      silica nanocomposite (PT/SBA-15) was prepared and used for extraction of
      essential oils with microwave-assisted distillation headspace solid phase
      microextraction (MA-HS-SPME) method. The prepared nanomaterials were immobilised
      on a stainless steel wire for fabrication of the SPME fibre. Using MA-HS-SPME
      followed by GC-MS, 24 compounds were separated and identified in Achillea
      tenuifolia, which mainly included limonene (28.6%), alpha-cadinol (12.7%),
      borneol (6.7%), caryophyllene oxide (3.2%), bornyl acetate (4.3%), camphene
      (3.2%) and para-cymene (2.3%). The experimental results showed that the
      polythiophene/hexagonally ordered silica nanocomposite fibres were suitable for
      the semi-quantitative study of the composition of essential oils in plant
      materials and for monitoring the variations in the volatile components of the
      plants. 

PMID- 25613725
TI  - Multitasking models for quantitative structure-biological effect relationships:
      current status and future perspectives to speed up drug discovery.
AB  - INTRODUCTION: Drug discovery is the process of designing new candidate
      medications for the treatment of diseases. Over many years, drugs have been
      identified serendipitously. Nowadays, chemoinformatics has emerged as a great
      ally, helping to rationalize drug discovery. In this sense, quantitative
      structure-activity relationships (QSAR) models have become complementary tools,
      permitting the efficient virtual screening for a diverse number of
      pharmacological profiles. Despite the applications of current QSAR models in the
      search for new drug candidates, many aspects remain unresolved. To date,
      classical QSAR models are able to predict only one type of biological effect
      (activity, toxicity, etc.) against only one type of generic target. AREAS
      COVERED: The present review discusses innovative and evolved QSAR models, which
      are focused on multitasking quantitative structure-biological effect
      relationships (mtk-QSBER). Such models can integrate multiple kinds of chemical
      and biological data, allowing the simultaneous prediction of pharmacological
      activities, toxicities and/or other safety profiles. EXPERT OPINION: The authors
      strongly believe, given the potential of mtk-QSBER models to simultaneously
      predict the dissimilar biological effects of chemicals, that they have much value
      as in silico tools for drug discovery. Indeed, these models can speed up the
      search for efficacious drugs in a number of areas, including fragment-based drug
      discovery and drug repurposing.

PMID- 25613726
TI  - Tuning carrier mobilities and polarity of charge transport in films of
      CuInSe(x)S(2-x) quantum dots.
AB  - CuInSe(x)S(2-x) quantum dot field-effect transistors show p-type, n-type, and
      ambipolar behaviors with carrier mobilities up to 0.03 cm(2) V(-1) s(-1).
      Although some design rules from studies of cadmium and lead containing quantum
      dots can be applied, remarkable differences are observed including a strong
      gating effect in as-synthesized nanocyrstals with long ligands.

PMID- 25613727
TI  - EBV and human cancer.

PMID- 25613729
TI  - EBV-driven B-cell lymphoproliferative disorders: from biology, classification and
      differential diagnosis to clinical management.
AB  - Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult
      population. EBV targets B-lymphocytes and achieves latent infection in a circular
      episomal form. Different latency patterns are recognized based on latent gene
      expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self
      aggregated, provides a proliferation signal via activating the nuclear factor
      kappa B, Janus kinase/signal transducer and activator of transcription,
      phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase
      pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape
      from apoptosis and gives a signal for cell cycle progression by enhancing cyclin
      dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by
      inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic
      cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL
      expression to promote B-cell survival. Recent studies have shown that ebv
      microRNAs can provide extra signals for cellular proliferation, cell cycle
      progression and anti-apoptosis. EBV is well known for association with various
      types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell
      neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of
      diseases, from benign to malignant. Here we review our current understanding of
      EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV
      associated B-cell lymphoproliferative disorders. 

PMID- 25613731
TI  - Genomic assays for Epstein-Barr virus-positive gastric adenocarcinoma.
AB  - A small set of gastric adenocarcinomas (9%) harbor Epstein-Barr virus (EBV) DNA
      within malignant cells, and the virus is not an innocent bystander but rather is
      intimately linked to pathogenesis and tumor maintenance. Evidence comes from
      unique genomic features of host DNA, mRNA, microRNA and CpG methylation profiles
      as revealed by recent comprehensive genomic analysis by The Cancer Genome Atlas
      Network. Their data show that gastric cancer is not one disease but rather
      comprises four major classes: EBV-positive, microsatellite instability (MSI),
      genomically stable and chromosome instability. The EBV-positive class has even
      more marked CpG methylation than does the MSI class, and viral cancers have a
      unique pattern of methylation linked to the downregulation of CDKN2A (p16) but
      not MLH1. EBV-positive cancers often have mutated PIK3CA and ARID1A and an
      amplified 9p24.1 locus linked to overexpression of JAK2, CD274 (PD-L1) and
      PDCD1LG2 (PD-L2). Multiple noncoding viral RNAs are highly expressed. Patients
      who fail standard therapy may qualify for enrollment in clinical trials targeting
      cancer-related human gene pathways or promoting destruction of infected cells
      through lytic induction of EBV genes. Genomic tests such as the GastroGenus
      Gastric Cancer Classifier are available to identify actionable variants in
      formalin-fixed cancer tissue of affected patients. 

PMID- 25613728
TI  - Epstein-Barr virus latent genes.
AB  - Latent Epstein-Barr virus (EBV) infection has a substantial role in causing many
      human disorders. The persistence of these viral genomes in all malignant cells,
      yet with the expression of limited latent genes, is consistent with the notion
      that EBV latent genes are important for malignant cell growth. While the EBV
      encoded nuclear antigen-1 (EBNA-1) and latent membrane protein-2A (LMP-2A) are
      critical, the EBNA-leader proteins, EBNA-2, EBNA-3A, EBNA-3C and LMP-1, are
      individually essential for in vitro transformation of primary B cells to
      lymphoblastoid cell lines. EBV-encoded RNAs and EBNA-3Bs are dispensable. In this
      review, the roles of EBV latent genes are summarized. 

PMID- 25613732
TI  - Modeling EBV infection and pathogenesis in new-generation humanized mice.
AB  - The development of highly immunodeficient mouse strains has allowed the
      reconstitution of functional human immune system components in mice. New
      generation humanized mice generated in this manner have been extensively used for
      modeling viral infections that are exclusively human tropic. Epstein-Barr virus
      (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B
      cell lymphoproliferative disease and EBV-associated hemophagocytic
      lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling
      rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV
      infection of humanized mice results in asymptomatic, persistent infection. Innate
      immune responses involving natural killer cells, EBV-specific adaptive T-cell
      responses restricted by human major histocompatibility and EBV-specific antibody
      responses are also elicited in humanized mice. EBV-associated T-/natural killer
      cell lymphoproliferative disease, by contrast, can be reproduced in a distinct
      mouse xenograft model. In this review, recent findings on the recapitulation of
      human EBV infection and pathogenesis in these mouse models, as well as their
      application to preclinical studies of experimental anti-EBV therapies, are
      described. 

PMID- 25613733
TI  - Epstein Barr virus-associated lymphoproliferative diseases: the virus as a
      therapeutic target.
AB  - Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express
      all EBV latent antigens (type III latency) in immunodeficient patients and
      limited antigens (type I and II latencies) in immunocompetent patients. Post
      transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting
      type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell
      proliferation remains unchecked because of the underlying immunosuppression. The
      restoration of anti-EBV immunity by EBV-specific T cells of either autologous or
      allogeneic origin has been shown to be safe and effective in PTLDs. Cellular
      therapy can be improved by establishing a bank of human leukocyte antigen
      characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and
      II latencies, the use of EBV-specific T cells is more limited, although the
      safety and efficacy of this therapy have also been demonstrated. The therapeutic
      role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with
      the advent of monoclonal antibodies and other targeted therapy. Another strategy
      involves the use of epigenetic approaches to induce EBV to undergo lytic
      proliferation when expression of the viral thymidine kinase renders host tumor
      cells susceptible to the cytotoxic effects of ganciclovir. Finally, the
      prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the
      occurrence of EBV+ LPDs. 

PMID- 25613730
TI  - Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders.
AB  - Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and
      latent infections that result in a variety of human diseases, including
      lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is
      related to its ability to infect and transform B lymphocytes into continuously
      proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been
      implicated in the development of T/natural killer cell lymphoproliferative
      diseases. Epstein-Barr virus encodes a series of products that mimic several
      growth, transcription and anti-apoptotic factors, thus usurping control of
      pathways that regulate diverse homeostatic cellular functions and the
      microenvironment. However, the exact mechanism by which Epstein-Barr virus
      promotes oncogenesis and inflammatory lesion development remains unclear. Epstein
      Barr virus-associated T/natural killer cell lymphoproliferative diseases often
      have overlapping clinical symptoms as well as histologic and immunophenotypic
      features because both lymphoid cell types derive from a common precursor.
      Accurate classification of Epstein-Barr virus-associated T/natural killer cell
      lymphoproliferative diseases is a prerequisite for appropriate clinical
      management. Currently, the treatment of most T/natural killer cell
      lymphoproliferative diseases is less than satisfactory. Novel and targeted
      therapies are strongly required to satisfy clinical demands. This review
      describes our current knowledge of the genetics, oncogenesis, biology, diagnosis
      and treatment of Epstein-Barr virus-associated T/natural killer cell
      lymphoproliferative diseases. 

PMID- 25613735
TI  - Cardiac Effects of Mad Honey Poisoning and Its Management in Emergency
      Department: A Review from Turkey.
AB  - Mad honey poisoning occurs when honey containing grayanotoxin is digested. The
      most common clinical signs and symptoms of poisoning involve findings of
      digestive system irritation, severe bradycardia and hypotension and central
      nervous system reaction. In this review, we aimed to underline the cardiac
      effects of mad honey poisoning. We also aimed to raise the awareness of
      physicians about early diagnosis and treatment of this rare entity. 

PMID- 25613736
TI  - Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means
      of NGAL and histology.
AB  - BACKGROUND: Ischemic acute kidney injury is a common occurrence in the
      perioperative period and in critical patients admitted to intensive care units.
      The reestablishment of blood supply may worsen injury through the ischemia
      reperfusion (I/R) mechanism. We investigated the effect of dexmedetomidine on the
      kidneys of rats subjected to an experimental I/R model. METHODS: 34 rats
      anesthetized with isoflurane was undergone right nephrectomy and randomly
      assigned to four groups: Control C (saline solution); Dexmedetomidine D
      (dexmedetomidine); Sham S (saline solution); Sham with Dexmedetomidine SD
      (dexmedetomidine). The serum levels of neutrophil gelatinase-associated lipocalin
      (NGAL) were measured at time-points T1 (following stabilization), T2 (ischemia),
      T3 (reperfusion), T4 (12 h after of I/R). The kidneys were subjected to
      histological examination. RESULTS: The NGAL levels were significantly higher at
      T4 compared with T1. Upon histological examination, the left kidneys in groups C
      and D exhibited a similar extent of cell injury. CONCLUSION: The levels of NGAL
      did not indicate either protection against or worsening of kidney injury.
      Histological examination for acute tubular necrosis showed that dexmedetomidine
      did not protect the kidneys from I/R.

PMID- 25613734
TI  - Evolutionary analysis of rubella viruses in mainland China during 2010-2012:
      endemic circulation of genotype 1E and introductions of genotype 2B.
AB  - Rubella remains a significant burden in mainland China. In this report, 667
      viruses collected in 24 of 31 provinces of mainland China during 2010-2012 were
      sequenced and analyzed, significantly extending previous reports on limited
      numbers of viruses collected before 2010. Only viruses of genotypes 1E and 2B
      were found. Genotype 1E viruses were found in all 24 provinces. Genotype 1E
      viruses were likely introduced into mainland China around 1997 and endemic
      transmission of primarily one lineage became established. Viruses reported here
      from 2010-2012 are largely in a single cluster within this lineage. Genotype 2B
      viruses were rarely detected in China prior to 2010. This report documents a
      previously undetected 2B lineage, which likely became endemic in eastern
      provinces of China between 2010 and 2012. Bayesian analyses were performed to
      estimate the evolutionary rates and dates of appearance of the genotype 1E and 2B
      viral linages in China. A skyline plot of viral population diversity did not
      provide evidence of reduction of diversity as a result of vaccination, but should
      be useful as a baseline for such reductions as vaccination programs for rubella
      become widespread in mainland China. 

PMID- 25613737
TI  - Relationships between interleukin-12B and interleukin-10 gene polymorphisms and
      hepatitis C in Chinese Han hemodialysis patients.
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV) commonly causes a chronic infection
      but portion of hemodialysis patients are able to resistant to HCV infection, even
      clear the virus naturally. Interleukin-10 (IL-10) and interleukin-12 (IL-12) are
      crucial regulators of the immune response to T-helper 1 (Th1) or T-helper 2 (Th2)
      categories and play a role in autoimmune and infectious diseases. This study was
      undertaken to investigate the possible association of genetic polymorphisms of 3'
      untranslated region (3'UTR) of the IL-12B (-1188) and IL-10 (-592 and -819) and
      hepatitis C in Chinese Han hemodialysis (HD) patients. METHODS: The genotyping of
      IL-12B 3'UTR and IL-10 -592 and -819 were performed by polymerase chain reaction
      (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: Compared
      with the IL-12B-AA genotype, CC and combined CC/AC genotypes were associated with
      a significant decreased risk of HCV infection in Chinese hemodialysis patients (p
      < 0.001). However, the IL-10-592 and -819 genotypes were not found significant
      difference both between the anti-HCV (+) and anti-HCV (-) patients (p > 0.05) and
      the persistent infection and viral clearance HD patients (p > 0.05). CONCLUSIONS:
      The present study indicated that the polymorphisms of IL-12B 3'UTR might
      contribute to the susceptibility of HCV infection in Chinese HD population.

PMID- 25613738
TI  - Renoprotection of Kolaviron against benzo (A) pyrene-induced renal toxicity in
      rats.
AB  - Benzo(a)pyrene (B[a]P), a polycyclic aromatic hydrocarbon generally formed from
      incomplete combustion of organic matter, reportedly causes renal injury and
      elicits a nephropathic response. The present study investigated the modulatory
      effect of Kolaviron, an isolated bioflavonoid from the seed of Garcinia kola, on
      renal toxicity induced by B[a]P in Wistar rats. Benzo[a]pyrene was administered
      at a dose of 10 mg/kg alone or in combination with Kolaviron at 100 and 200 mg/kg
      for 15 d. Administration of B[a]P alone resulted in significant increase in
      plasma levels of urea and creatinine in the treated rats. Moreover, B[a]P
      exposure significantly decreased the activities of superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx) and glutathione-s-transferase (GST)
      as well as glutathione (GSH) level in the kidneys of treated rats. Conversely,
      myeloperoxidase (MPO) activity, hydrogen peroxide (H2O2) and malondialdehyde
      (MDA) levels were markedly elevated in kidneys of B[a]P-treated rats compared
      with control. Further, B[a]P exposure significantly decreased the circulatory
      concentrations of triiodothyronine (T3) and T3/T4 ratio without affecting
      thyroxine (T4) in the treated rats. Light microscopy revealed tubular lumen with
      numerous protein casts in kidneys of rats exposed to B[a]P alone. Kolaviron co
      treatment significantly improved the renal antioxidant status, thyroid gland
      function and restored the renal histology, thus demonstrating the protective
      effect of Kolaviron in B[a]P-treated rats. Dietary inclusion of Kolaviron could
      exert protective effects against renal toxicity resulting from B[a]P exposure.

PMID- 25613740
TI  - Removal of a urethrolith via ovariohysterovaginectomy after endoscopic
      retropulsion in a rabbit with uterine adenocarcinoma.

PMID- 25613739
TI  - Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress,
      inflammation, apoptosis, and autophagy in rats.
AB  - Gentamicin is commonly used against gram-negative microorganisms. Its therapeutic
      use is mainly limited by nephrotoxicity. This study was aimed at evaluating the
      effect of rutin on oxidative stress, inflammation, apoptosis, and autophagy in
      gentamicin-induced nephrotoxicity in rats. The rats were treated with saline
      intraperitoneally (group I), 150 mg/kg of rutin orally (group II), 80 mg/kg of
      gentamicin intraperitoneally for 8 d (group III), or 150 mg/kg of rutin plus 80
      mg/kg of gentamicin (group IV). The serum urea, creatinine, kidney
      malondialdehyde (MDA), and reduced glutathione (GSH) levels and superoxide
      dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and
      protein concentration were measured, and renal histopathology analysis and
      immunohistochemical staining were performed. Rutin pretreatment attenuated
      nephrotoxicity induced by gentamicin by reducing the urea, creatinine, and MDA
      levels and increasing the SOD, CAT, and GPx activity, and the GSH levels. The
      rutin also inhibited inducible nitric oxide synthase (iNOS), cleaved caspase-3
      and light chain 3B (LC3B), as evidenced by immunohistochemical staining. The
      present study demonstrates that rutin exhibits antioxidant, anti-inflammatory,
      anti-apoptotic, and anti-autophagic effects and that it attenuates gentamicin
      induced nephrotoxicity in rats.

PMID- 25613741
TI  - Polymorphism of the E-cadherin gene CDH1 is associated with susceptibility to
      vitiligo.
AB  - Vitiligo is a depigmenting disorder characterized by loss of functional
      melanocytes from the epidermis. Experimental data suggest that defective
      melanocyte adhesion may underlie the pathogenesis of the disease. In particular,
      association between vitiligo and genetic variants of the DDR1 gene involved in
      melanocyte adhesion has been recently published. A subsequent, independent study
      revealed lower expression of DDR1 in vitiligo lesions. Here, we expand this
      investigation by testing for association between vitiligo and polymorphisms of
      CDH1, IL1B and NOV (formerly CCN3), genes belonging to the DDR1 adhesion pathway,
      in two population samples of distinct design. Our results reveal that alleles of
      marker rs10431924 of the CDH1 gene are associated with vitiligo, especially in
      the presence of autoimmune comorbidities. 

PMID- 25613742
TI  - Identification and characterization of pleiotropic and co-located resistance loci
      to leaf rust and stripe rust in bread wheat cultivar Sujata.
AB  - KEY MESSAGE: Two new co-located resistance loci, QLr.cim - 1AS/QYr.cim - 1AS and
      QLr.cim - 7BL/YrSuj , in combination with Lr46 / Yr29 and Lr67/Yr46 , and a new
      leaf rust resistance quantitative trait loci, conferred high resistance to rusts
      in adult plant stage. The tall Indian bread wheat cultivar Sujata displays high
      and low infection types to leaf rust and stripe rust, respectively, at the
      seedling stage in greenhouse tests. It was also highly resistant to both rusts at
      adult plant stage in field trials in Mexico. The genetic basis of this resistance
      was investigated in a population of 148 F5 recombinant inbred lines (RILs)
      derived from the cross Avocet * Sujata. The parents and RIL population were
      characterized in field trials for resistance to leaf rust during 2011 at El
      Batan, and 2012 and 2013 at Ciudad Obregon, Mexico, and for stripe rust during
      2011 and 2012 at Toluca, Mexico; they were also characterized three times for
      stripe rust at seedling stage in the greenhouse. The RILs were genotyped with
      diversity arrays technology and simple sequence repeat markers. The final genetic
      map was constructed with 673 polymorphic markers. Inclusive composite interval
      mapping analysis detected two new significant co-located resistance loci, QLr.cim
      1AS/QYr.cim-1AS and QLr.cim-7BL/YrSuj, on chromosomes 1AS and 7BL, respectively.
      The chromosomal position of QLr.cim-7BL overlapped with the seedling stripe rust
      resistance gene, temporarily designated as YrSuj. Two previously reported
      pleiotropic adult plant resistance genes, Lr46/Yr29 and Lr67/Yr46, and a new leaf
      rust resistance quantitative trait loci derived from Avocet were also mapped in
      the population. The two new co-located resistance loci are expected to contribute
      to breeding durable rust resistance in wheat. Closely linked molecular markers
      can be used to transfer all four resistance loci simultaneously to modern wheat
      varieties.

PMID- 25613744
TI  - Questionnaire survey on the use of a novel artificial pancreas by intensive care
      unit nurses.
AB  - The introduction of a color liquid-crystal display (LCD) on a novel artificial
      pancreas (STG-55, Nikkiso Co. Ltd. Tokyo, Japan) allowed nurses to more easily
      monitor changes in patients' blood glucose levels, compared to the previous model
      (STG-22). This study was conducted to examine the hypothesis that the STG-55
      provided nurses with a feeling of security due to the introduction of the LCD
      screen. A questionnaire survey was conducted 6 months after the STG-55 was
      introduced (Survey 2012), among intensive care unit (ICU) nurses who had used
      both the STG-22 and the STG-55 for patient glycemic control. The results were
      then compared with the results from a questionnaire survey that was conducted
      after the STG-22 was introduced (Survey 2006). All ICU nurses (n = 19) responded
      to Survey 2012, and 95% of these nurses had responded to Survey 2006 (n = 19).
      After the introduction of the STG-22, 11 nurses (58%) reported becoming conscious
      of anxiety regarding hypoglycemia when they performed conventional glucose
      control with the sliding scale method. This anxiety awareness increased
      significantly (19 nurses, 100%; p < 0.01) after the STG-55 was introduced.
      However, there were no significant differences in the proportion of respondents
      who requested improvements in the blood withdrawal process. In conclusion, the
      results of our survey indicate that all ICU nurses became conscious of anxiety
      regarding the risk of hypoglycemia when using the conventional sliding scale
      method after the introduction of the STG-55. However, the respondents were not
      satisfied with the STG-55, due to difficulties encountered during blood
      withdrawal.

PMID- 25613743
TI  - Structure-activity analysis of thiourea analogs as inhibitors of UT-A and UT-B
      urea transporters.
AB  - Small-molecule inhibitors of urea transporter (UT) proteins in kidney have
      potential application as novel salt-sparing diuretics. The urea analog
      dimethylthiourea (DMTU) was recently found to inhibit the UT isoforms UT-A1
      (expressed in kidney tubule epithelium) and UT-B (expressed in kidney vasa recta
      endothelium) with IC50 of 2-3 mM, and was shown to have diuretic action when
      administered to rats. Here, we measured UT-A1 and UT-B inhibition activity of 36
      thiourea analogs, with the goal of identifying more potent and isoform-selective
      inhibitors, and establishing structure-activity relationships. The analog set
      systematically explored modifications of substituents on the thiourea including
      alkyl, heterocycles and phenyl rings, with different steric and electronic
      features. The analogs had a wide range of inhibition activities and
      selectivities. The most potent inhibitor, 3-nitrophenyl-thiourea, had an IC50 of
      ~0.2 mM for inhibition of both UT-A1 and UT-B. Some analogs such as 4-nitrophenyl
      thiourea were relatively UT-A1 selective (IC50 1.3 vs. 10 mM), and others such as
      thioisonicotinamide were UT-B selective (IC50>15 vs. 2.8 mM).

PMID- 25613745
TI  - Preliminary results of 'liver-first' reverse management for advanced and
      aggressive synchronous colorectal liver metastases: a propensity-matched
      analysis.
AB  - BACKGROUND: Although a 'liver-first' approach recently has been advocated in
      treating synchronous colorectal metastases, little is known about how results
      compare with those of the classical approach among patients with similar grades
      of liver metastases. METHODS: Propensity-score matching was used to select study
      subjects. Oncologic outcomes were compared between 10 consecutive patients with
      unresectable advanced and aggressive synchronous colorectal liver metastases
      treated with the reverse strategy and 30 comparable classically treated patients.
      RESULTS: Numbers of recurrence sites and recurrent tumors irrespective of
      recurrence sites were greater in the reverse group then the classic group (p =
      0.003 and p = 0.015, respectively). Rates of freedom from recurrence in the
      remaining liver and of freedom from disease also were poorer in the reverse group
      than in the classical group (p = 0.009 and p = 0.043, respectively). Among
      patients treated with 2-stage hepatectomy, frequency of microvascular invasion
      surrounding macroscopic metastases at second resection was higher in the reverse
      group than in the classical group (p = 0.011). CONCLUSIONS: Reverse approaches
      may be feasible in treating synchronous liver metastases, but that strategy
      should be limited to patients with less liver tumor burden.

PMID- 25613746
TI  - Margaret McCartney: Don't be bullied into prescribing Tamiflu.

PMID- 25613747
TI  - Effects of glucose-dependent insulinotropic polypeptide on gastric emptying,
      glycaemia and insulinaemia during critical illness: a prospective, double blind,
      randomised, crossover study.
AB  - INTRODUCTION: Insulin is used to treat hyperglycaemia in critically ill patients
      but can cause hypoglycaemia, which is associated with poorer outcomes. In health
      glucose-dependent insulinotropic polypeptide (GIP) is a potent glucose-lowering
      peptide that does not cause hypoglycaemia. The objectives of this study were to
      determine the effects of exogenous GIP infusion on blood glucose concentrations,
      glucose absorption, insulinaemia and gastric emptying in critically ill patients
      without known diabetes. METHODS: A total of 20 ventilated patients (Median age 61
      (range: 22 to 79) years, APACHE II 21.5 (17 to 26), BMI 28 (21 to 40) kg/m(2))
      without known diabetes were studied on two consecutive days in a randomised,
      double blind, placebo controlled, cross-over fashion. Intravenous GIP (4
      pmol/kg/min) or placebo (0.9% saline) was infused between T = -60 to 300 minutes.
      At T0, 100 ml of liquid nutrient (2 kcal/ml) containing 3-O-Methylglucose (3
      OMG), 100 mcg of Octanoic acid and 20 MBq Tc-99 m Calcium Phytate, was
      administered via a nasogastric tube. Blood glucose and serum 3-OMG (an index of
      glucose absorption) concentrations were measured. Gastric emptying, insulin and
      glucagon levels and plasma GIP concentrations were also measured. RESULTS: While
      administration of GIP increased plasma GIP concentrations three- to four-fold (T
      = -60 23.9 (16.5 to 36.7) versus T = 0 84.2 (65.3 to 111.1); P <0.001) and plasma
      glucagon (iAUC300 4217 (1891 to 7715) versus 1232 (293 to 4545) pg/ml.300
      minutes; P = 0.04), there were no effects on postprandial blood glucose (AUC300
      2843 (2568 to 3338) versus 2819 (2550 to 3497) mmol/L.300 minutes; P = 0.86),
      gastric emptying (AUC300 15611 (10993 to 18062) versus 15660 (9694 to 22618)
      %.300 minutes; P = 0.61), glucose absorption (AUC300 50.6 (22.3 to 74.2) versus
      64.3 (9.9 to 96.3) mmol/L.300 minutes; P = 0.62) or plasma insulin (AUC300 3945
      (2280 to 6731) versus 3479 (2316 to 6081) mU/L.300 minutes; P = 0.76).
      CONCLUSIONS: In contrast to its profound insulinotropic effect in health, the
      administration of GIP at pharmacological doses does not appear to affect
      glycaemia, gastric emptying, glucose absorption or insulinaemia in the critically
      ill patient. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12612000488808. Registered 3 May 2012.

PMID- 25613748
TI  - RNAi screening of developmental toolkit genes: a search for novel wing genes in
      the red flour beetle, Tribolium castaneum.
AB  - The amazing array of diversity among insect wings offers a powerful opportunity
      to study the mechanisms guiding morphological evolution. Studies in Drosophila
      (the fruit fly) have identified dozens of genes important for wing development.
      These genes are often called candidate genes, serving as an ideal starting point
      to study wing development in other insects. However, we also need to explore
      beyond the candidate genes to gain a more comprehensive view of insect wing
      evolution. As a first step away from the traditional candidate genes, we utilized
      Tribolium (the red flour beetle) as a model and assessed the potential
      involvement of a group of developmental toolkit genes (embryonic patterning
      genes) in beetle wing development. We hypothesized that the highly pleiotropic
      nature of these developmental genes would increase the likelihood of finding
      novel wing genes in Tribolium. Through the RNA interference screening, we found
      that Tc-cactus has a less characterized (but potentially evolutionarily
      conserved) role in wing development. We also found that the odd-skipped family
      genes are essential for the formation of the thoracic pleural plates, including
      the recently discovered wing serial homologs in Tribolium. In addition, we
      obtained several novel insights into the function of these developmental genes,
      such as the involvement of mille-pattes and Tc-odd-paired in metamorphosis.
      Despite these findings, no gene we examined was found to have novel wing-related
      roles unique in Tribolium. These results suggest a relatively conserved nature of
      developmental toolkit genes and highlight the limited degree to which these genes
      are co-opted during insect wing evolution. 

PMID- 25613749
TI  - The comparative study of five sex-determining proteins across insects unveils
      high rates of evolution at basal components of the sex determination cascade.
AB  - In insects, the sex determination cascade is composed of genes that interact with
      each other in a strict hierarchical manner, constituting a coadapted gene complex
      built in reverse order from bottom to top. Accordingly, ancient elements at the
      bottom are expected to remain conserved ensuring the correct functionality of the
      cascade. In the present work, we have studied the levels of variation displayed
      by five key components of the sex determination cascade across 59 insect species,
      including Sex-lethal, transformer, transformer-2, fruitless, doublesex, and
      sister-of-Sex-lethal (a paralog of Sxl encompassing sex-independent functions).
      Surprisingly, our results reveal that basal components of the cascade (doublesex,
      fruitless) seem to evolve more rapidly than previously suspected. Indeed, in the
      case of Drosophila, these proteins evolve more rapidly than the master regulator
      Sex-lethal. These results agree with the notion suggesting that genes involved in
      early aspects of development will be more constrained due to the large
      deleterious pleiotropic effects of mutations, resulting in increased levels of
      purifying selection at top positions of the cascade. The analyses of the
      selective episodes involved in the recruitment of Sxl into sex-determining
      functions further support this idea, suggesting the presence of bursts of
      adaptive selection in the common ancestor of drosophilids, followed by the onset
      of purifying selection preserving the master regulatory role of this protein on
      top of the Drosophila sex determination cascade. Altogether, these results
      underscore the importance of the position of sex determining genes in the
      cascade, constituting a major constraint shaping the molecular evolution of the
      insect sex determination pathway. 

PMID- 25613750
TI  - Methylation and expression of the tumour suppressor, PRDM5, in colorectal cancer
      and polyp subgroups.
AB  - BACKGROUND: PRDM5 is an epigenetic regulator that has been recognized as an
      important tumour suppressor gene. Silencing of PRDM5 by promoter hypermethylation
      has been demonstrated in several cancer types and PRDM5 loss results in
      upregulation of the Wnt pathway and increased cellular proliferation. PRDM5 has
      not been extensively investigated in specific subtypes of colorectal cancers. We
      hypothesized it would be more commonly methylated and inactivated in serrated
      pathway colorectal cancers that are hallmarked by a BRAF V600E mutation and a
      methylator phenotype, compared to traditional pathway cancers that are BRAF wild
      type. METHODS: Cancer (214 BRAF mutant, 122 BRAF wild type) and polyp (59
      serrated polyps, 40 conventional adenomas) cohorts were analysed for PRDM5
      promoter methylation using MethyLight technology. PRDM5 protein expression was
      assessed by immunohistochemistry in cancers and polyps. Mutation of PRDM5 was
      analysed using cBioPortal's publicly available database. RESULTS: BRAF mutant
      cancers had significantly more frequent PRDM5 promoter methylation than BRAF wild
      type cancers (77/214,36% vs 4/122,3%; p<0.0001). Serrated type polyps had a lower
      methylation rate than cancers but were more commonly methylated than conventional
      adenomas (6/59,10% vs 0/40,0%). PRDM5 methylation was associated with advanced
      stages of presentation (p<0.05) and the methylator phenotype (p=0.03). PRDM5
      protein expression was substantially down-regulated in both BRAF mutant and wild
      type cancer cohorts (92/97,95% and 39/44,89%). The polyp subgroups showed less
      silencing than the cancers, but similar rates were found between the serrated and
      conventional polyp cohorts (29/59, 49%; 23/40, 58% respectively). Of 295
      colorectal cancers, PRDM5 was mutated in only 6 (2%) cancers which were all BRAF
      wild type. CONCLUSIONS: Serrated pathway colorectal cancers demonstrated early
      and progressive PRDM5 methylation with advancing disease. Interestingly, PRDM5
      protein expression was substantially reduced in all polyp types and more so in
      cancers which also indicates early and increasing PRDM5 down-regulation with
      disease progression. Methylation may be contributing to gene silencing in a
      proportion of BRAF mutant cancers, but the large extent of absent protein
      expression indicates other mechanisms are also responsible for this. These data
      suggest that PRDM5 is a relevant tumour suppressor gene that is frequently
      targeted in colorectal tumourigenesis.

PMID- 25613751
TI  - Enhanced vaccination effect against influenza by prebiotics in elderly patients
      receiving enteral nutrition.
AB  - AIM: We investigated the effect of prebiotics on the immunological response after
      influenza vaccination in enterally fed elderly individuals. The intervention
      group was given an enteral formula containing lactic acid bacteria-fermented milk
      products. In addition, two different types of other prebiotics, galacto
      oligosaccharide and bifidogenic growth stimulator, were also given. The two
      prebiotics improved intestinal microbiota differently. In a control group, a
      standard formula without prebiotics was given. METHODS: An enteral formula with
      (intervention group [F]) or without (control group [C]) prebiotics was given
      through percutaneous endoscopic gastrostomy to elderly participants for 10 weeks.
      Influenza vaccine was inoculated at week 4. Nutritional and biochemical indices,
      intestinal micro bacteria and immunological indices were analyzed. RESULTS: The
      Bifidobacterium count in groups F and C at week 0 was 6.4 +/- 1.9 and 6.6 +/- 3.0
      (log10 [count/g feces]), respectively. Although the count in group C decreased at
      week 10, the count in group F increased. The Bacteroides count in group F
      increased from 10.7 +/- 0.9 to 11.4 +/- 0.5, but decreased in group C from 11.2
      +/- 0.2 to 10.7 +/- 0.4. Although the enhanced titers of H1N1, H3N2 and B
      antigens against the vaccine decreased thereafter in group C, these enhanced
      titers in group F could be maintained. CONCLUSION: Our findings suggest that
      prebiotics affect the intestinal microbiota and might maintain the antibody
      titers in elderly individuals.

PMID- 25613752
TI  - Curcumin treatment suppresses CCR7 expression and the differentiation and
      migration of human circulating fibrocytes.
AB  - BACKGROUND/AIM: Recent studies have demonstrated that circulating fibrocytes
      contribute to the formation and development of fibrosis. Curcumin, a polyphenolic
      compound isolated from turmeric, has been shown to have anti-fibrotic effects in
      various organs. We and others have demonstrated that curcumin beneficially
      affects the development of fibrosis. However the effect of curcumin on
      circulating fibrocytes has not been reported. METHODS: Human circulating
      fibrocytes were isolated from leukocyte concentrates of healthy human donors and
      identified based on the expression of CD34, CD45, collagen I (COLI), and
      chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used
      to evaluate cell viability. The effect of curcumin on the differentiation and
      migration of human circulating fibrocytes was evaluated by immunofluorescence
      staining, flow cytometry and a transwell migration assay. Transforming growth
      factor (TGF)-beta1 secretion was examined by ELISA. RESULTS: Curcumin treatment
      (72 h; 20 MUM) significantly decreased the expression of COL I, alpha-SMA and
      CCR7, as well as TGF-betal secretion, in human circulating fibrocytes. The
      inhibitory effect of curcumin on the differentiation and migration of human
      circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway,
      in particular by reducing CCR7 expression. These observed effects may be
      beneficial in resolving fibrosis by suppressing TGF-beta1 secretion. CONCLUSION:
      Our results suggest that curcumin has the potential to suppress the
      differentiation and migration of circulating fibrocytes, which would provide new
      explanation for curcumin's application in the development of fibrosis in various
      organs.

PMID- 25613753
TI  - SRS06, a new semisynthetic andrographolide derivative with improved anticancer
      potency and selectivity, inhibits nuclear factor-kappaB nuclear binding in the
      A549 non-small cell lung cancer cell line.
AB  - BACKGROUND: Andrographolide has been reported with anticancer and anti
      inflammatory properties through the inhibition of the activity of signaling
      molecules such as v-Src, nuclear factor-kappaB (NF-kappaB), STAT3, and PI3K. NF
      kappaB has been proven to promote cancer cell survival, and targeting this
      pathway will halt the growth of cancer cells. Efforts have been made to produce
      semisynthetic derivatives of andrographolide with improved anticancer potency and
      selectivity. Subsequently, the effect of a selected derivative, 3,14,19
      tripropionylandrographolide (SRS06), was tested for its action against NF-kappaB.
      METHODS: Screening against 60 US National Cancer Institute (NCI) human cancer
      cell lines representing leukemia and non-small cell lung (NSCL), colon, CNS,
      melanoma, ovarian, renal, prostate, and breast cancers was performed to determine
      the tumor type selectivity and potency of SRS06. Microculture tetrazolium, 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and sulforhodamine B
      assays were used to determine the in vitro anticancer activity, while Western
      blot studies were performed to ascertain the inhibitory effect of SRS06 on the NF
      kappaB signaling cascade. The TransAMTM p65 assay kit was used to determine NF
      kappaB p65 DNA binding activity in the NSCL cancer cell line A549. RESULTS: From
      the NCI screening, SRS06 was found to exhibit potent growth-inhibitory effects on
      multiple cancer cell lines with 10-fold lower 50% growth inhibition (GI50)
      compared with andrographolide. It was also discerned that the compound
      preferentially targeted melanoma, CNS, renal, colon, ovarian, prostate, and NSCL
      cancer cell lines. The DNA fragmentation assay indicated that the main mode of
      cell death of SRS06-treated A549 cells was via apoptosis. At 5 umol/l the
      compound decreased NF-kappaB protein expression and caused a significant
      reduction in the nuclear p65 DNA binding activity. CONCLUSION: SRS06 displayed
      improved anticancer selectivity and potency when compared with andrographolide.
      We alluded its anticancer activity to its effect of inhibiting NF-kappaB nuclear
      binding.

PMID- 25613754
TI  - Quantum clock synchronization with a single qudit.
AB  - Clock synchronization for nonfaulty processes in multiprocess networks is
      indispensable for a variety of technologies. A reliable system must be able to
      resynchronize the nonfaulty processes upon some components failing causing the
      distribution of incorrect or conflicting information in the network. The task of
      synchronizing such networks is related to Byzantine agreement (BA), which can
      classically be solved using recursive algorithms if and only if less than one
      third of the processes are faulty. Here we introduce a nonrecursive quantum
      algorithm, based on a quantum solution of the detectable BA, which achieves clock
      synchronization in the presence of arbitrary many faulty processes by using only
      a single quantum system. 

PMID- 25613755
TI  - Variable expression of Alagille syndrome in a family with a new JAG1 gene
      mutation.
AB  - We report the case of a patient with tetralogy of Fallot with absent pulmonary
      valve and familial Alagille syndrome who successfully underwent cardiac repair.
      The patient's sister had liver and congenital heart disease. The father had
      undergone liver transplantation but showed no significant cardiac abnormalities.
      A yet-unknown mutation of the JAG1 gene was discovered in this family with
      variable expression of Alagille syndrome. 

PMID- 25613756
TI  - Gelatin microcapsules for enhanced microwave tumor hyperthermia.
AB  - Local and rapid heating by microwave (MW) irradiation is important in the
      clinical treatment of tumors using hyperthermia. We report here a new thermo-seed
      technique for the highly efficient MW irradiation ablation of tumors in vivo
      based on gelatin microcapsules. We achieved 100% tumor elimination in a mouse
      model at an ultralow power of 1.8 W without any side-effects. The results of MTT
      assays, a hemolysis test and the histological staining of organs indicated that
      the gelatin microcapsules showed excellent compatibility with the physiological
      environment. A possible mechanism is proposed for MW hyperthermia using gelatin
      microcapsules. We also used gelatin microcapsules capped with CdTe quantum dots
      for in vivo optical imaging. Our study suggests that these microcapsules may have
      potential applications in imaging-guided cancer treatment. 

PMID- 25613757
TI  - Upregulation of PAX2 promotes the metastasis of esophageal cancer through
      interleukin-5.
AB  - BACKGROUND/AIMS: This study investigated the clinical relevance and biological
      function of paired box gene 2 (PAX2) in esophageal squamous cell carcinoma
      (ESCC). METHODS/RESULTS: Results showed that PAX2 expression was significantly
      increased in tumor tissues and that its expression correlated with the ESCC stage
      (P = 0.001), lymph node metastasis (pN, P = 0.019) and lymphatic invasion (P =
      0.005) in 120 ESCC tissue specimens by immunohistochemistry. Furthermore, PAX2
      overexpression resulted in markedly reduced cell proliferation but increased
      metastasis capacity in ESCC TE-1 and Eca-109 cells. Knockdown of PAX2 expression
      with a short hairpin RNA confirmed a role in the promotion of metastasis in ESCC
      cells. mRNA microarray screening revealed that PAX2 overexpression affected
      multiple genes that function in multiple pathways. Interleukin-5 (IL-5), which
      was induced by PAX2 and has been shown to promote tumor metastasis, was further
      studied in greater detail. Two PAX2 binding sites were identified in the IL-5
      promoter, and PAX2 was observed to stimulate IL-5 promoter activity and IL-5
      expression in esophageal cancer cells. Chromatin immunoprecipitation (ChIP)
      confirmed the direct binding of PAX2 in the IL-5 promoter. The expression of PAX2
      mRNA significantly correlated with that of IL-5 in normal esophageal and ESCC
      tissues. CONCLUSION: These findings demonstrate that PAX2 is overexpressed in
      esophageal carcinoma and IL-5 is identified as PAX2's effector for metastasis.

PMID- 25613758
TI  - Previous exposure to Cyclosporine A and periodontal breakdown in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of previous
      exposure to Cyclosporine A (CsA) on experimental periodontitis in rats. DESIGN:
      Forty rats were divided into 4 groups: Control (CON); Cyclosporine A (CsA), which
      received daily doses of 10mg/kg CsA; Ligature (LIG), which received an insertion
      of a cotton ligature around the mandibular 1st molar at day 30; and Ligature and
      CsA (CsAL), which were treated with CsA and the cotton ligature. At day 60 of the
      experiment, animals were sacrificed, and groups were compared with regards to
      Alkaline Phosphatase (AP) activity, gingival overgrowth, periodontal bone support
      (PBS), bone resorption at furcation ligament area (LA) and TRAP+ cells. Data were
      analyzed by ANOVA/Tukey and Kruskal-Wallis and were considered to be
      statistically significant at 5% level. RESULTS: CsA and LIG groups showed similar
      gingival area, which was higher than that in the CON and lower than in the CsAL
      group (p=0.001). The ratio between epithelial area and connective area for the
      CON group was similar to the CsA group and higher than that for the CsAL and LIG
      groups (p=0.0334). Mean percentage of PBS for the CON group was similar to that
      for the CsAL group and higher than that of the CsA and LIG groups (p=0.0007). No
      difference was observed regarding AP (p=0.2806) and TRAP+ cells (p=0.3995) among
      experimental groups. Mean values for LA of CON were similar to CsA, and both were
      statistically lower than the CsAL and LIG groups (p=0.0172). CONCLUSION: Based on
      these results, we posit that previous exposure to CsA may influence gingival
      overgrowth, but not bone loss, in rats with experimental periodontitis.

PMID- 25613759
TI  - Gaze constancy in upright and inverted faces.
AB  - The dual-route model (Otsuka, Mareschal, Calder, & Clifford, 2014) posits that
      constancy in the perception of gaze direction across lateral head rotation
      depends on the integration of information from the eye region and information
      about head rotation. Incorporation of information about head rotation serves to
      compensate for the change in eye-region information when viewing a rotated head.
      We tested the ability of this model to predict the magnitude of Wollaston's
      effect: When eyes from a frontal pose are inserted into an angled face, the
      perceived direction of gaze appears attracted towards the direction of the head.
      The framework of the dual-route model explains Wollaston's effect as a result of
      the misapplication of this same integration operation without any change in eye
      region information. To test this explanation, we compared the magnitude of the
      integration occurring for Wollaston's effect to that for normal faces. Here,
      participants performed categorical judgment of gaze direction across head
      rotation poses in three image conditions: normal face, eyes-only, and Wollaston.
      Integration of eye and head information was inferred by comparing the effect of
      pose between the eyes-only condition and the normal face condition, and by
      examining the effect of pose in the Wollaston condition. Consistent with the dual
      route model, the magnitude of integration was similar between the normal face
      condition and the Wollaston condition. Further, upright and inverted faces
      yielded similar levels of gaze constancy, showing that the dual-route model
      applies to the perception of gaze direction in inverted faces as well as in
      upright faces. 

PMID- 25613760
TI  - Partial modal completion under occlusion: what do modal and amodal percepts
      represent?
AB  - In the occlusion illusion, a partly occluded object is perceived as though it
      were less occluded than it actually is (Palmer, Brooks, & Lai, 2007). We confirm
      and extend this finding using a stimulus with a moving occluder. In agreement
      with Palmer et al.'s (2007) findings and their partial-modal-completion
      hypothesis, we found that the illusion is indeed related to the sensory evidence
      for occlusion. Our experiments also confirm their speculation that the occlusion
      illusion involves an intriguing, seemingly paradoxical percept. In our
      experiments, subjects viewed an opaque disk with an open sector rotating in front
      of a background and indicated the perceived angular extent (a) of the occluder
      and (b) of the part of the background experienced as directly visible through the
      open sector. While the former was judged quite accurately, the latter was clearly
      overestimated. Thus, the angular extent of the background experienced as occluded
      and the extent experienced as directly visible sum to more than 360 degrees ,
      which makes the total percept an impossible figure. We argue that the key to
      resolving this paradox is to question the seemingly self-evident assumption that
      occluded and unoccluded portions of a visual scene are represented by amodal and
      modal percepts, respectively. Instead, we propose that visual percepts are
      experienced as modal whenever they are based on sufficiently conclusive sensory
      evidence and are otherwise experienced as amodal. Functionally, this perceptual
      representation of the conclusiveness of the sensory evidence underlying
      perceptual inferences might be more useful than estimates about optical
      visibility. 

PMID- 25613761
TI  - Target-distractor similarity has a larger impact on visual search in school-age
      children than spacing.
AB  - In typically developing children, crowding decreases with increasing age. The
      influence of target-distractor similarity with respect to orientation and element
      spacing on visual search performance was investigated in 29 school-age children
      with normal vision (4- to 6-year-olds [N = 16], 7- to 8-year-olds [N = 13]).
      Children were instructed to search for a target E among distractor Es (feature
      search: all flanking Es pointing right; conjunction search: flankers in three
      orientations). Orientation of the target was manipulated in four directions:
      right (target absent), left (inversed), up, and down (vertical). Spacing was
      varied in four steps: 0.04 degrees , 0.5 degrees , 1 degrees , and 2 degrees .
      During feature search, high target-distractor similarity had a stronger impact on
      performance than spacing: Orientation affected accuracy until spacing was 1
      degrees , and spacing only influenced accuracy for identifying inversed targets.
      Spatial analyses showed that orientation affected oculomotor strategy: Children
      made more fixations in the "inversed" target area (4.6) than the vertical target
      areas (1.8 and 1.9). Furthermore, age groups differed in fixation duration: 4- to
      6-year-old children showed longer fixation durations than 7- to 8-year-olds at
      the two largest element spacings (p = 0.039 and p = 0.027). Conjunction search
      performance was unaffected by spacing. Four conclusions can be drawn from this
      study: (a) Target-distractor similarity governs visual search performance in
      school-age children, (b) children make more fixations in target areas when target
      distractor similarity is high, (c) 4- to 6-year-olds show longer fixation
      durations than 7- to 8-year-olds at 1 degrees  and 2 degrees  element spacing,
      and (d) spacing affects feature but not conjunction search-a finding that might
      indicate top-down control ameliorates crowding in children. 

PMID- 25613762
TI  - Tacrolimus prolonged release (Envarsus(r)): a review of its use in kidney and
      liver transplant recipients.
AB  - Tacrolimus prolonged release (Envarsus(r); henceforth referred to as tacrolimus
      PR) is a new, once-daily, prolonged-release tacrolimus formulation, utilizing a
      drug delivery technology designed to enhance the bioavailability of drugs with
      low water solubility by creating a solid solution of the drug. This article
      reviews the pharmacological properties of tacrolimus PR and its clinical efficacy
      and tolerability in adult kidney and liver transplant recipients. In phase III
      trials, tacrolimus PR was noninferior to tacrolimus immediate release (IR; twice
      daily) in both de novo and stable, previously treated kidney transplant
      recipients, and had a similar tolerability profile. Preliminary efficacy data
      from phase II trials in de novo and stable, previously treated liver transplant
      recipients imply that tacrolimus PR is effective in these patient groups;
      however, more data would be of interest. Pharmacokinetic analyses demonstrated
      that tacrolimus PR is associated with a higher bioavailability, reduced peak
      trough concentration fluctuation ratio, lower mean values for percentage degree
      of fluctuation and percentage degree of swing, and a longer time to maximum
      concentration than tacrolimus IR. Tacrolimus PR is a promising addition to the
      treatment options available for kidney and liver transplant recipients.

PMID- 25613763
TI  - The effect of shift work on red blood cell distribution width.
AB  - Limited research demonstrates that shift work (e.g., evening shift, night shift,
      rotating shift) increases the risk of certain health outcomes, such as
      hypertriglyceridemia and metabolic syndrome. Red blood cell distribution width
      (RDW), which is commonly assessed and reported by physicians, is a novel
      biomarker of cardiovascular disease. However, no study has examined the
      association of shift work on RDW, which was the purpose of this study. Data from
      the 2005-2010 NHANES were used. RDW was assessed from a blood sample; shift work
      was assessed from a questionnaire, and various demographic,
      behavioral/psychological, occupational, and biological parameters were included
      as covariates. The fully adjusted model showed that the odds of having an
      elevated RDW for women on rotating shift vs. day shift increased by 46% (OR=1.46;
      95% CI: 1.03-2.08). Women on a rotating shift had increased odds of having an
      elevated RDW, which is concerning as elevated RDW increases the risk of
      cardiovascular disease and mortality. Health care professionals are encouraged to
      include questions about organization of work schedules and their tolerance of
      such schedules during the patient's consultation. 

PMID- 25613764
TI  - The effect of long-term wastewater irrigation on accumulation and transfer of
      heavy metals in Cupressus sempervirens leaves and adjacent soils.
AB  - Wastewater reuse for agriculture is an important management strategy in areas
      with limited freshwater resources, yielding potential economic and environmental
      benefits. Here the effects of long-term irrigation with wastewater on the
      nutrient contents of green and senesced leaves of Cupressus sempervirens L. were
      assessed for three planted forests in Egypt. Stoichiometric ratios, transfer
      factors for nutrients from soil to plant and enrichment factors in contaminated
      soils were estimated and compared to a ground water irrigated control site. Under
      wastewater irrigation, C. sempervirens transferred most of the estimated
      nutrients, particularly heavy metals, from green to senesced leaves. This could
      be a self-protecting mechanism under continuous wastewater irrigation. The
      accumulation of four metals (Zn, Mn, Cu and Cd) with transfer factors>1 for
      wastewater-irrigated trees, indicated the ability for metal accumulation of C.
      sempervirens. Stoichiometric ratios decreased under wastewater irrigation
      compared to the control site and global trends, which suggests nutrient disorders
      in these plants. The values of enrichment factors in the wastewater-irrigated
      soils showed remarkable availability and distribution of metals. Decreased
      resorption of metals by senesced leaves of C. sempervirens will add considerable
      amount of these metals to the soils, which will likely have adverse affects on
      the desert ecosystem components. 

PMID- 25613765
TI  - Rainfall variability drives interannual variation in N2O emissions from a humid,
      subtropical pasture.
AB  - Variations in interannual rainfall totals can lead to large uncertainties in
      annual N2O emission budget estimates from short term field studies. The
      interannual variation in nitrous oxide (N2O) emissions from a subtropical pasture
      in Queensland, Australia, was examined using continuous measurements of automated
      chambers over 2 consecutive years. Nitrous oxide emissions were highest during
      the summer months and were highly episodic, related more to the size and
      distribution of rain events than soil water content. Over 48% of the total N2O
      emitted was lost in just 16% of measurement days. Interannual variation in annual
      N2O estimates was high, with cumulative emissions increasing with decreasing
      rainfall. Cumulative emissions averaged 1826.7+/-199.9 g N2O-N ha(-1) yr(-1) over
      the two year period, though emissions from 2008 (2148+/-273 g N2O-N ha(-1) yr(
      1)) were 42% higher than 2007 (1504+/-126 g N2O-N ha(-1) yr(-1)). This increase
      in annual emissions coincided with almost half of the summer precipitation from
      2007 to 2008. Emissions dynamics were chiefly driven by the distribution and size
      of rain events which varied on a seasonal and annual basis. Sampling frequency
      effects on cumulative N2O flux estimation were assessed using a jackknife
      technique to inform future manual sampling campaigns. Test subsets of the daily
      measured data were generated for the pasture and two adjacent land-uses
      (rainforest and lychee orchard) by selecting measured flux values at regular time
      intervals ranging from 1 to 30 days. Errors associated with weekly sampling were
      up to 34% of the sub-daily mean and were highly biased towards overestimation if
      strategically sampled following rain events. Sampling time of day also played a
      critical role. Morning sampling best represented the 24 hour mean in the pasture,
      whereas sampling at noon proved the most accurate in the shaded rainforest and
      lychee orchard.

PMID- 25613766
TI  - Short tests to couple N2O emission mitigation and nitrogen removal strategies for
      landfill leachate recirculation.
AB  - Landfills implemented with onsite leachate recirculation can efficiently remove
      pollutants, but currently they are reckoned as N2O emission hot spots. In this
      project, we evaluated the relationship between N2O emission and nitrogen (N)
      removal efficiency with different types of leachate recirculated. Nitrate
      supplemented leachate showed low N2O emission rates with the highest N removal
      efficiency (~70%), which was equivalent to ~1% nitrogen emitted as N2O. Although
      in nitrite containing leachates' N removal efficiencies also reached to ~60%,
      their emitted N2O comprised ~40% of total removed nitrogen. Increasing nitrogen
      load promoted N2O emission and N removal efficiency, except in ammonia type
      leachate. When the ratio of BOD to total nitrogen increased from 0.2 to 0.4, the
      N2O emission flux from nitrate supplemented leachate decreased from ~25 to <0.5
      MUg N/kg-soil.h. We argue prior to leachate in situ recirculation, sufficient pre
      aeration is critical to mitigate N2O surges and simultaneously enhance nitrogen
      removal efficiency.

PMID- 25613767
TI  - Sediment composition for the assessment of water erosion and nonpoint source
      pollution in natural and fire-affected landscapes.
AB  - Water erosion is a leading cause of soil degradation and a major nonpoint source
      pollution problem. Many efforts have been undertaken to estimate the amount and
      size distribution of the sediment leaving the field. Multi-size class water
      erosion models subdivide eroded soil into different sizes and estimate the
      aggregate's composition based on empirical equations derived from agricultural
      soils. The objective of this study was to evaluate these equations on soil
      samples collected from natural landscapes (uncultivated) and fire-affected soils.
      Chemical, physical, and soil fractions and aggregate composition analyses were
      performed on samples collected in the Chilean Patagonia and later compared with
      the equations' estimates. The results showed that the empirical equations were
      not suitable for predicting the sediment fractions. Fine particles, including
      primary clay, primary silt, and small aggregates (<53 MUm) were over-estimated,
      and large aggregates (>53 MUm) and primary sand were under-estimated. The
      uncultivated and fire-affected soils showed a reduced fraction of fine particles
      in the sediment, as clay and silt were mostly in the form of large aggregates.
      Thus, a new set of equations was developed for these soils, where small
      aggregates were defined as particles with sizes between 53 MUm and 250 MUm and
      large aggregates as particles>250 MUm. With r(2) values between 0.47 and 0.98,
      the new equations provided better estimates for primary sand and large
      aggregates. The aggregate's composition was also well predicted, especially the
      silt and clay fractions in the large aggregates from uncultivated soils
      (r(2)=0.63 and 0.83, respectively) and the fractions of silt in the small
      aggregates (r(2)=0.84) and clay in the large aggregates (r(2)=0.78) from fire
      affected soils. Overall, these new equations proved to be better predictors for
      the sediment and aggregate's composition in uncultivated and fire-affected soils,
      and they reduce the error when estimating soil loss in natural landscapes.

PMID- 25613768
TI  - Considerations for the development of shale gas in the United Kingdom.
AB  - The United States shale gas boom has precipitated global interest in the
      development of unconventional oil and gas resources. Recently, government
      ministers in the United Kingdom started granting licenses that will enable
      companies to begin initial exploration for shale gas. Meanwhile, concern is
      increasing among the scientific community about the potential impacts of shale
      gas and other types of unconventional natural gas development (UGD) on human
      health and the environment. Although significant data gaps remain, there has been
      a surge in the number of articles appearing in the scientific literature, nearly
      three-quarters of which has been published since the beginning of 2013. Important
      lessons can be drawn from the UGD experience in the United States. Here we
      explore these considerations and argue that shale gas development policies in the
      UK and elsewhere should be informed by empirical evidence generated on
      environmental, public health, and social risks. Additionally, policy decisions
      should take into account the measured effectiveness of harm reduction strategies
      as opposed to hypothetical scenarios and purported best practices that lack
      empirical support. 

PMID- 25613769
TI  - Concentrations of hormones, pharmaceuticals and other micropollutants in
      groundwater affected by septic systems in New England and New York.
AB  - Septic-system discharges can be an important source of micropollutants (including
      pharmaceuticals and endocrine active compounds) to adjacent groundwater and
      surface water systems. Groundwater samples were collected from well networks
      tapping glacial till in New England (NE) and sandy surficial aquifer New York
      (NY) during one sampling round in 2011. The NE network assesses the effect of a
      single large septic system that receives discharge from an extended health care
      facility for the elderly. The NY network assesses the effect of many small septic
      systems used seasonally on a densely populated portion of Fire Island. The data
      collected from these two networks indicate that hydrogeologic and demographic
      factors affect micropollutant concentrations in these systems. The highest
      micropollutant concentrations from the NE network were present in samples
      collected from below the leach beds and in a well downgradient of the leach beds.
      Total concentrations for personal care/domestic use compounds, pharmaceutical
      compounds and plasticizer compounds generally ranged from 1 to over 20 MUg/L in
      the NE network samples. High tris(2-butoxyethyl phosphate) plasticizer
      concentrations in wells beneath and downgradient of the leach beds (>20 MUg/L)
      may reflect the presence of this compound in cleaning agents at the extended
      health-care facility. The highest micropollutant concentrations for the NY
      network were present in the shoreline wells and reflect groundwater that is most
      affected by septic system discharges. One of the shoreline wells had personal
      care/domestic use, pharmaceutical, and plasticizer concentrations ranging from
      0.4 to 5.7 MUg/L. Estradiol equivalency quotient concentrations were also highest
      in a shoreline well sample (3.1 ng/L). Most micropollutant concentrations
      increase with increasing specific conductance and total nitrogen concentrations
      for shoreline well samples. These findings suggest that septic systems serving
      institutional settings and densely populated areas in coastal settings may be
      locally important sources of micropollutants to adjacent aquifer and marine
      systems.

PMID- 25613770
TI  - Field transplantation of the bivalve Scrobicularia plana along a mercury gradient
      in Ria de Aveiro (Portugal): uptake and depuration kinetics.
AB  - The bioaccumulation and depuration capabilities of mercury by the edible bivalve
      Scrobicularia plana was studied in a coastal lagoon (Ria de Aveiro, Portugal)
      through a transplantation experiment. Little information on this topic is
      available in the literature, especially concerning different tissues' responses
      to contaminant exposure, but the present study is one of the few works that can
      surpass this knowledge gap. Organisms from a reference area were transplanted to
      two different contaminated areas in the Ria de Aveiro. In both areas, the
      bivalves (i.e., entire organism, digestive gland and the rest of the organism)
      presented a similar saturation model of mercury accumulation, the digestive gland
      being the tissue that reached the highest concentrations after 25 days of
      exposure to the contaminant. During this short uptake period, the transplanted
      organisms reached 20-30% of the concentrations observed in resident contaminated
      organisms. After the exposure period, the organisms were transplanted to a clean
      area for more than 25 days of depuration. At the end of the transplantation
      period, organisms lost approximately 50% of their mercury body burden (60%: the
      entire organism and digestive gland; 35%: gills and 40%: the rest of the
      organism) and the ones from the least contaminated site almost reached the
      concentrations recorded in the reference area. So, the results suggest that S.
      plana is a promising biomonitoring species, since it accumulates the contaminant
      in a considerable extent quite rapidly and at the same time it has a low metal
      retention capacity (low biological half-life) when exposed to clean sediments.

PMID- 25613771
TI  - Has the impact of temperature on mortality really decreased over time?
AB  - Many studies have reported that the temperature effect on mortality has decreased
      over time. However, most of those studies did not consider lag times longer than
      10 days, which is frequently used to explore its effect net out compensatory
      effect (harvesting) and lag effects. We sought to examine the temporal variation
      of the temperature effect on mortality, considering both a lag effect and
      mortality displacement. Time-series analysis was conducted with lag of
      temperature up to 21 days on all-cause, cardiovascular, cerebrovascular, and
      respiratory deaths. We applied a series of time-windows, 8 years long, with which
      we compared the oldest to more recent intervals and took consecutive annual
      variation, excluding an interannual harvesting effect. At the 99th percentile (29
      degrees C), relative to the 90th percentile (25 degrees C), we found a decreasing
      trend of heat effect on concurrent days whereas the risk of cardiovascular deaths
      increased over time. Cumulative risks of deaths increased recently except for
      respiratory disease. At the 10th percentile (-1 degrees C) relative to the 25th
      percentile (4 degrees C), cumulative cold effects on cardiovascular and
      respiratory mortality have emerged recently. Our study showed differences in the
      temporal variation in the temperature effect on mortality at concurrent day and
      in cumulative term. It is suggested that the time-varying nature of the
      temperature-mortality relationship depends not only on suggested factors, such as
      improvements in technology and infrastructure, and human physiological
      acclimatization, but also mortality displacement and lagged effects. Further
      studies on its complex nature are needed to provide relevant evidence for public
      health policy making.

PMID- 25613772
TI  - Establishment and performance of an experimental green roof under extreme
      climatic conditions.
AB  - Green roofs alter the surface energy balance and can help in mitigating urban
      heat islands. However, the cooling of green roofs due to evapotranspiration
      strongly depends on the climatic conditions, and vegetation type and density. In
      the Southern Central Plains of the United States, extreme weather events, such as
      high winds, heat waves and drought conditions pose challenges for successful
      implementation of green roofs, and likely alter their standard performance. The
      National Weather Center Experimental Green Roof, an interdisciplinary research
      site established in 2010 in Norman, OK, aimed to investigate the ecological
      performance and surface energy balance of green roof systems. Starting in May
      2010, 26 months of vegetation studies were conducted and the radiation balance,
      air temperature, relative humidity, and buoyancy fluxes were monitored at two
      meteorological stations during April-October 2011. The establishment of a
      vegetative community trended towards prairie plant dominance. High mortality of
      succulents and low germination of grasses and herbaceous plants contributed to
      low vegetative coverage. In this condition succulent diversity declined.
      Bouteloua gracilis and Delosperma cooperi showed typological dominance in harsh
      climatic conditions, while Sedum species experienced high mortality. The plant
      community diversified through volunteers such as Euphorbia maculate and Portulaca
      maculate. Net radiation measured at a green-roof meteorological station was
      higher than at a control station over the original, light-colored roofing
      material. These findings indicate that the albedo of the green roof was lower
      than the albedo of the original roofing material. The low vegetative coverage
      during the heat and drought conditions in 2011, which resulted in the dark
      substrate used in the green roof containers being exposed, likely contributed to
      the low albedo values. Nevertheless, air temperatures and buoyancy fluxes were
      often lower over the green roof indicating that higher evapotranspiration rates
      compensated for the higher net radiation at the green roof.

PMID- 25613773
TI  - Potential ecological risk of hazardous elements in different land-use urban soils
      of Bangladesh.
AB  - Soil pollution, influenced by both the natural and anthropogenic factors,
      significantly reduces environmental quality. In this study, six hazardous
      elements (Cr, Ni, Cu, As, Cd and Pb) in 12 different land-use urban soils from
      Bangladesh were assessed. The ranges of Cr, Ni, Cu, As, Cd and Pb in studied
      soils were 2.4-1258, 8.3-1044, 9.7-823, 8.7-277, 1.8-80 and 13-842 mg/kg,
      respectively. More than 70% of soil samples exceeded the Dutch target value for
      Ni, Cu, As, Cd and Pb concentration in soil, indicating a potential risk to the
      environment. Certain indices, including the enrichment factor (EF), pollution
      load index (PLI) and contamination factor (Cf(i)), were used to assess the
      ecological risk posed by hazardous elements in soils. The mean range of PLI was
      1.5-10, indicating progressive deterioration of soil due to metal contamination.
      However, the Cf(i) values of Cd ranged from 3.7 to 35 revealed that the examined
      soils were strongly impacted by Cd. Considering the severity of potential
      ecological risk for single metal (Er(i)), the descending order of contaminants
      was Cd>As>Cu>Pb>Ni>Cr. In view of the potential ecological risk (PER), soils from
      all land uses showed considerable to very high potential ecological risk.

PMID- 25613775
TI  - Selective colorimetric NO(g) detection based on the use of modified gold
      nanoparticles using click chemistry.
AB  - A new colorimetric system for NO(g) detection is described. The detection method
      is based on the aggregation of modified AuNPs through a Cu(I) catalyzed click
      reaction promoted by the in situ reduction of Cu(II) by NO.

PMID- 25613774
TI  - Scleroderma renal crisis.
AB  - OBJECTIVES: To discuss the pathophysiology, risk factors, clinical
      manifestations, diagnosis, treatment, prevention, and outcomes of scleroderma
      renal crisis (SRC), a serious yet potentially treatable complication of
      scleroderma (systemic sclerosis). METHODS: A PubMed search for articles published
      up until April 2014 was conducted using the following keywords: scleroderma,
      systemic sclerosis, scleroderma renal crisis, renal, treatment, and prognosis.
      Literature was carefully reviewed, and different risk factors, treatment options,
      prognostic factors, and survival data were assessed. RESULTS: SRC occurs in about
      10% of all patients with scleroderma. It is characterized by malignant
      hypertension and progressive renal failure. Around 10% of SRC cases may present
      with normal blood pressure, termed normotensive renal crisis. The
      etiopathogenesis is presumed to be a series of insults to the kidneys resulting
      in endothelial injury, intimal proliferation, and narrowing of renal arterioles
      leading to decreased blood flow, hyperplasia of the juxtaglomerular apparatus,
      hyperreninemia, and accelerated hypertension. Risk factors include rapid skin
      thickening, use of certain medications such corticosteroids or cyclosporine, new
      onset microangiopathic hemolytic anemia and/or thrombocytopenia, cardiac
      complications (pericardial effusion, congestive heart failure, and/or
      arrhythmias), large joint contractures, and presence of anti-RNA polymerase III
      antibody. Since the 1970s, with the advent of angiotensin-converting enzyme (ACE)
      inhibitors, mortality associated with SRC decreased from 76% to <10%. Some
      patients may progress to end-stage renal disease and need dialysis. Renal
      transplantation has improved survival, though SRC may recur in transplanted
      kidneys. CONCLUSIONS: More than 60 years after its initial description, SRC still
      remains an important cause of morbidity and mortality in scleroderma. Since the
      advent of ACE inhibitors, the prognosis of SRC has improved substantially. Prompt
      diagnosis and treatment may help prevent adverse outcomes and improve survival.

PMID- 25613776
TI  - Elevated plasma haptoglobin concentrations following parturition are associated
      with elevated leukocyte responses and decreased subsequent reproductive
      efficiency in multiparous Holstein dairy cows.
AB  - The objectives were to describe the relationship between the intensity of the
      acute phase response and the metabolic status and leukocyte responses of early
      postpartum, multiparous cows and determine if subsequent reproductive performance
      was impaired in cows with a greater acute phase response. Peripheral blood was
      collected from 240 Holstein cows, 2-8 days in milk and 2nd-8th parity from 8
      dairies in Western TX and Eastern NM across 5 days (n=6 cows/dairy/day). Plasma
      concentrations of haptoglobin were measured and cows were classified as Low (1st
      quartile), Moderate (2nd and 3rd quartiles), or High (4th quartile) responders.
      Metabolic measurements included: plasma glucose, urea nitrogen, non-esterified
      fatty acids and beta-hydroxybutyrate concentrations. Leukocyte response
      measurements included: total leukocyte counts and differentials, neutrophil
      surface expression of L-selectin, neutrophil oxidative burst capacity when co
      cultured with an environmental Escherichia coli, as well as the secretion of
      tumor necrosis factor-alpha and interferon-gamma when diluted whole blood were co
      cultured with lipopolysaccharide and phytohemagglutinin-P, respectively. All data
      are reported as Low, Moderate, and High haptoglobin responders. Plasma
      haptoglobin concentrations ranged from below the limit of detection to 8.4
      MUg/mL, 8.5 to 458 MUg/mL, and 459 to 1757 MUg/mL. The High cows had more severe
      neutropenia (3.45, 3.31, and 2.23 +/- 0.31 * 10(6)cells/mL; P=0.013)
      Additionally, the innate leukocyte responses of the High cows were stimulated as
      evident by increased secretion of tumor necrosis factor-alpha (568, 565, and 730
      +/- 73.4 pg/mL; P=0.003), surface expression of L-selectin on neutrophils (70.8,
      71.9, and 119.8 +/- 7.9 geometric mean fluorescence intensity; P=0.001), and
      greater neutrophil oxidative burst capacity (37.9, 40.4, and 47.9 +/- 0.31
      geometric mean fluorescence intensity; P=0.002). In contrast, the secretion of
      the T-lymphocyte derived cytokine, interferon-gamma, was suppressed in both the
      Moderate and High cows when compared with Low cows (718, 408, and 322 +/- 92.2
      pg/mL; P=0.01). Haptoglobin class had an overall effect on days to conception
      (P=0.039). The number of days in milk for 75% of the cows in each haptoglobin
      class to conceive increased from 123 d in the Low group, 139 d in the Moderate
      group, and 183 d in the High group. These data indicate that a stronger acute
      phase response during the early postpartum period that is characterized by an
      activated innate immune system and a suppressed mitogen-induced interferon-gamma
      secretion resulted in impaired reproductive efficiency, and this response was
      consistent across the large commercial dairy herds sampled.

PMID- 25613777
TI  - Chicken bone marrow-derived dendritic cells maturation in response to infectious
      bursal disease virus.
AB  - Infectious bursal disease virus (IBDV) is highly contagious disease which easily
      lead to immunosuppression and a decreased response to vaccinations in young
      chicken. Since dendritic cells (DCs) are crucial to induce immunity and their
      maturation and functions are influenced by microbial and environmental stimuli,
      we investigated the effects of inactivated IBDV and IBDV on chicken DC activation
      and maturation. Chicken bone marrow-derived dendritic cells (chBM-DCs) cultured
      in complete medium (including recombinant chicken: granulocyte-macrophage colony
      stimulating factor and interleukin 4) expressed high levels of MHC-II and the
      putative CD11c. After LPS or virus stimulation, chBM-DCs displayed the typical
      morphology of DCs. In addition, stimulation by LPS or viruses significantly
      elevated chBM-DCs surface expression levels of CD40 and CD86 molecules, as well
      as the ability to induce T-cell proliferative response, compared to the non
      stimulated chBM-DCs. Interestingly, inactive IBDV showed stronger ability to up
      regulate expression levels of CD40 and CD86 molecules and stimulate naive T cells
      proliferation than live IBDV. These results revealed that live viruses infection
      impaired DC maturation and functions, probably explaining why chickens infected
      with IBDV fails to trigger an effective specific immune response or develop
      immune memory. 

PMID- 25613778
TI  - Detection of the pufferfish toxin tetrodotoxin in European bivalves, England,
      2013 to 2014.
AB  - We report the first detection of tetrodotoxins (TTX) in European bivalve
      shellfish. We demonstrate that TTX is present within the temperate waters of the
      United Kingdom, along the English Channel, and can accumulate in filter-feeding
      molluscs. The toxin is heat-stable and thus it cannot be eliminated during
      cooking. While quantified concentrations were low in comparison to published
      minimum lethal doses for humans, the results demonstrate that the risk to
      shellfish consumers should not be discarded.

PMID- 25613780
TI  - Widespread implementation of EUCAST breakpoints for antibacterial susceptibility
      testing in Europe.
AB  - The European Committee on Antimicrobial Susceptibility Testing (EUCAST) was
      established to harmonise clinical antimicrobial breakpoints and to define
      breakpoints for new agents in Europe. Data from the European Antimicrobial
      Resistance Surveillance Network (EARS-Net) external quality assessment (EQA)
      exercises from 2009 to 2012, from the United Kingdom External Quality Assessment
      Scheme (UK NEQAS) from November 2009 to March 2013 and data collected by EUCAST
      through a questionnaire in the first quarter of 2013 were analysed to investigate
      implementation of EUCAST guidelines in Europe. A rapid change to use of EUCAST
      breakpoints was observed over time. Figures for implementation of EUCAST
      breakpoints at the end of the studied period were 61.2% from EARSNet data and
      73.2% from UK NEQAS data. Responses to the EUCAST questionnaire indicated that
      EUCAST breakpoints were used by over 50% of laboratories in 18 countries, by 10
      to 50% of laboratories in eight countries and by less than 10% in seven
      countries. The EUCAST disk diffusion method was used by more than 50% of
      laboratories in 12 countries, by 10 to 50% of laboratories in ten countries and
      by less than 10% in eleven countries. EUCAST guidelines implementation is
      essential to ensure consistent clinical reporting of antimicrobial susceptibility
      results and antimicrobial resistance surveillance.

PMID- 25613779
TI  - 2012/13 influenza vaccine effectiveness against hospitalised influenza
      A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals.
AB  - While influenza vaccines aim to decrease the incidence of severe influenza among
      high-risk groups, evidence of influenza vaccine effectiveness (IVE) among the
      influenza vaccine target population is sparse. We conducted a multicentre test
      negative case-control study to estimate IVE against hospitalised laboratory
      confirmed influenza in the target population in 18 hospitals in France, Italy,
      Lithuania and the Navarre and Valencia regions in Spain. All hospitalised
      patients aged >=18 years, belonging to the target population presenting with
      influenza-like illness symptom onset within seven days were swabbed. Patients
      positive by reverse transcription polymerase chain reaction for influenza virus
      were cases and those negative were controls. Using logistic regression, we
      calculated IVE for each influenza virus subtype and adjusted it for month of
      symptom onset, study site, age and chronic conditions. Of the 1,972 patients
      included, 116 were positive for influenza A(H1N1)pdm09, 58 for A(H3N2) and 232
      for influenza B. Adjusted IVE was 21.3% (95% confidence interval (CI): -25.2 to
      50.6; n=1,628), 61.8% (95% CI: 26.8 to 80.0; n=557) and 43.1% (95% CI: 21.2 to
      58.9; n=1,526) against influenza A(H1N1) pdm09, A(H3N2) and B respectively. Our
      results suggest that the 2012/13 IVE was moderate against influenza A(H3N2) and B
      and low against influenza A(H1N1) pdm09.

PMID- 25613781
TI  - Letter to the editor: vaccinating healthcare workers: evidence and ethics.

PMID- 25613782
TI  - Author's reply: vaccinating healthcare workers: ethics and strategic behaviour.

PMID- 25613784
TI  - Lumpectomy specimen margins are not reliable in predicting residual disease in
      breast conserving surgery.
AB  - BACKGROUND: In breast conserving surgery, the concordance between lumpectomy
      margin (LM) status and the status of the corresponding lumpectomy cavity remains
      uncertain. METHODS: We analyzed pathology reports of lumpectomies from 2004 to
      2006. We included those which contained both ink-directed LM and complete (>=4)
      separate corresponding shaved cavity margins (SCMs). SCM pathology was used as a
      surrogate for lumpectomy cavity status, to determine the predictive value of LM
      for residual disease. RESULTS: Pathology from 1,201 pairs of LM and SCM from 242
      patients was compared. LM status predicted corresponding lumpectomy cavity status
      with 50.9% sensitivity, 69.5% specificity, 35% positive predictive value, and
      81.4% negative predictive value, giving an overall accuracy of 64.9%.
      CONCLUSIONS: Oriented LMs are not reliable for predicting lumpectomy cavity
      status, and therefore not reliable for directing re-excision. Taking complete,
      oriented SCMs at the time of lumpectomy may improve accuracy compared with
      traditional LM assessment.

PMID- 25613785
TI  - The diagnostic and surgical challenges of massive localized lymphedema.
AB  - BACKGROUND: Massive localized lymphedema (MLL) is a rare entity first described
      in 1998 in patients with morbid obesity; the incidence is rising with the
      increased prevalence of morbid obesity. This report defines the clinical
      presentation and surgical challenges in 6 patients with MLL. METHODS: The MLL in
      6 patients with morbid obesity (weight range 270 to 585 lbs) involved the thigh
      in 3 patients, the calf in 1 patient, and the abdomen in 2 patients. The time
      from onset to presentation averaged 3 years (range 1 to 8 years). Two thigh
      lesions precluded ambulation because both legs could not be on the ground
      simultaneously; the 2 abdominal lesions were too heavy to permit ambulation.
      RESULTS: The surgical excision required the use of pulleys to elevate the MLL
      tissues, which, on excision, weighed between 24 and 78 lbs. A long oval
      horizontal incision and a long transverse incision were used for the 2 abdominal
      lesions. Long horizontal oval limb incisions with multiple perpendicular cross
      incisions had to be used to excise MLL in the 4 limb lesions. In 2 cases, the
      vessel-sealing device was employed successfully for dissecting subcutaneous
      edematous tissue. Loose wound closure permitted postoperative lymph leakage,
      which continued for 3 to 8 weeks. The histology demonstrated fibrotic lymphatic
      tissue with vascular and lymphatic proliferation and edema; all patients did
      well. CONCLUSIONS: MLL is rare and is best treated by surgical excision
      facilitated by pulleys and imaginative incisions to obtain primary closure. Long
      term follow-up is necessary to assess for subsequent liposarcoma or angiosarcoma.

PMID- 25613786
TI  - Candida dubliniensis and Candida albicans differentiation by colony morphotype in
      Sabouraud-triphenyltetrazolium agar.
AB  - BACKGROUND: Candida dubliniensis is a germ tube and chlamydoconidia producing
      Candida species that may be misidentified as Candida albicans. Molecular-based
      methods are the most reliable techniques for C. albicans and C. dubliniensis
      differentiation. However, accurate, quick and inexpensive phenotypic tests are
      needed to be used in low-complexity mycology laboratories. AIMS: To evaluate
      colony morphotypes on Sabouraud-triphenyltetrazolium agar as a tool for C.
      dubliniensis and C. albicans differentiation. METHODS: The morphology of 126 C.
      albicans and C. dubliniensis strains was evaluated and compared with their
      identification by molecular methods. RESULTS: The method showed 100% sensitivity
      and specificity when color and the presence or absence of large white mycelial
      halo was evaluated. CONCLUSIONS: Colony morphotype on Sabouraud
      triphenyltetrazolium agar should be considered as a new tool to differentiate C.
      dubliniensis and C. albicans.

PMID- 25613787
TI  - Skeletal Muscle Cell Behavior After Physical Agent Treatments.
AB  - Apoptosis is essential for skeletal muscle development and homeostasis. It has
      been frequently involved in several muscle myopathies and sarcopenia, as well as
      in denervation, in disuse and acute strenuous or eccentric physical exercise. In
      this work skeletal muscle cell death, induced in vitro by a variety of physical
      triggers, has been investigated. C2C12 myoblasts and myotubes were exposed to UVB
      for 30 min, hyperthermia for 1 h at 43  degrees C, low pH for 3 h, hypothermia
      for 4h at 0 - 6 degrees C, all followed by 2 - 4 h recovery. Their effects have
      been analysed by means of morpho- functional and molecular approaches. After UVB
      radiation, hyperthermia and acidosis, morphological apoptotic features and in
      situ DNA fragmentation appeared, more evident in myoblasts. Interestingly,
      apoptotic, non apoptotic and necrotic nuclei could be occasionally observed
      within the same myotube. Low pH induced apoptosis and necrosis, both
      characterized by swollen nuclei. In all these experimental conditions, the
      molecular investigations revealed a caspase pathway involvement in inducing cell
      death. Differently, hypothermia showed a scant and initial chromatin margination,
      in the presence of a diffused autophagic component. In this case, in situ DNA
      fragmentation and caspase activation have not been detected. Myoblasts and
      myotubes appeared sensitive to physical agents, some of which, induced apoptotic
      cell death. Moreover, hypothermia exposure seemed to enhance autophagic response,
      thus representing a way to delay trauma-correlated muscle inflammation. This
      study permits to highlight skeletal muscle cell behavior in response to physical
      agents, by adding important information to muscle cell death knowledge. UVB
      radiation and hyperthermia, usually used in clinical therapy, have also adverse
      effects on skeletal muscle such as myonuclei loss and cell death, contributing to
      muscle mass decrease. Acidosis occurs physiologically in muscular fatigue,
      reducing not only the athlete performance, but causing muscle cell damage or
      death too. Finally, hypothermia, stimulating the autophagic response, could have
      a key role in muscle injury prevention.

PMID- 25613788
TI  - Anticancer Advances of Matrine and Its Derivatives.
AB  - As the second leading cause of death in the world, the total number caused by
      cancer in 2008 is 1.4 million. The great cancer incidence worldwide increases the
      search for new, safer and efficient anticancer agents (especially to find the new
      structures and more active anticancer drugs from the natural products) aiming the
      prevention or the cure of such illness. For a century, matrine (an alkaloid
      isolated from sophorae flavescens Ait.) has been widely studied in the field of
      cancer. This review briefly describes the progress of matrine, its derivatives
      and their anticancer activity.

PMID- 25613790
TI  - Pharmacological treatment of idiopathic pulmonary fibrosis: an update.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and almost invariably lethal
      disease that affects primarily older adults. After a decade of negative (or
      inconsistent) results, two recent clinical trials have demonstrated that slowing
      disease progression with medication is possible. An improved understanding of
      disease pathogenesis, epidemiology, and diagnostic criteria has been key to this
      success. Yet, this is only the beginning. It is hoped that continuous efforts by
      dedicated scientists and clinicians, patient organizations, health authorities,
      and pharmaceutical companies will soon lead to the development of more effective
      and better-tolerated treatment strategies for this devastating disease. 

PMID- 25613789
TI  - Recent advances in the treatment of adult T-cell leukemia-lymphomas.
AB  - Recent advances in treatment for adult T-cell leukemia-lymphoma (ATL) are
      reviewed herein. It is currently possible to select a therapeutic strategy for
      ATL and predict prognosis by classification of patients by clinical subtypes and
      clinicopathological factors. Although the overall survival (OS) of patients with
      ATL has increased marginally because of advances in chemotherapy, further
      prolongation of survival might be difficult with conventional chemotherapy alone.
      Promising results have been reported for antiviral therapy using zidovudine and
      interferon-alpha, and, indeed, antiviral therapy is currently the standard
      treatment for patients with ATL in western countries. Remarkably, the 5-year OS
      rates are 100% for both the smoldering-type and chronic-type ATL. Recently,
      treatments for ATL have included allogeneic hematopoietic stem cell
      transplantation and molecular targeted therapies. Furthermore, the anti-CCR4
      monoclonal antibody mogamulizumab has been shown to have marked cytotoxic effects
      on ATL cells, especially in the leukemic type of ATL. In the lymphoma type of
      ATL, the response rate may be improved by combining mogamulizumab with
      chemotherapy. It should be recognized that prevention of infection from carriers
      of human T-cell leukemia virus type-I and transfer of the virus from mother to
      infant are crucial issues for the eradication of ATL. 

PMID- 25613791
TI  - Anatomical basis of the reverse lateral plantar artery perforator flap design.
AB  - BACKGROUND: This study aims to explore the characteristics of the formation and
      topography of lateral plantar artery perforators to identify a repair procedure
      for defects in the forefoot region. METHODS: Thirty-three cadavers were available
      for this anatomical study. The tuberosity of the fifth metatarsal bone was
      adopted as the anatomical landmark. The details of the lateral plantar artery
      perforators and the anastomosis between the lateral plantar artery perforators
      and other arteries of lateral foot were recorded. RESULTS: The perforators from
      the base and head of the fifth metatarsal bone constantly originate from the
      lateral plantar artery in the area of tuberosity of the fifth metatarsal, run
      along the medial side of the fifth metatarsal, then travel between the fifth
      metatarsal bone and lateral muscle group, pierce the aponeurosis, vascularize the
      skin of the anterior lateral plantar region, and finally anastomose with the
      lateral tarsal artery and the fourth dorsal metatarsal artery. At the point of
      origin, the mean sizes of the perforator of the fifth metatarsal base and head
      were 1.3 +/- 0.2 and 0.9 +/- 0.3 mm (mean +/- SEM), respectively. The pedicle
      lengths were 2.6 +/- 0.3 and 3.8 +/- 0.5 cm, indicating the possibility of a free
      perforator flap. CONCLUSION: The lateral plantar artery perforators are presented
      constant. The forefoot region can be repaired by the reverse perforator flap
      harvested pedicled with either the lateral plantar artery perforator from the
      base or head of the fifth metatarsal bone.

PMID- 25613792
TI  - Three-dimensional evaluation of the danger zone of ethmoidal foramens on the
      frontoethmoidal suture line on the medial orbital wall.
AB  - INTRODUCTION: It is clear that the importance of the ethmoidal foramen (EF) is
      based on its vascular contents. The frontoethmoidal suture (FS) line is
      recommended as more reliable navigational landmark for identifying the EF.
      MATERIALS AND METHODS: The vertical orientation between the EF and the FS line
      was studied in 188 orbits using a computer software program. RESULTS: 146
      anterior EFs (77.7 %) and 42 anterior EFs (22.3 %) were situated in the FS line
      as intrasutural and extrasutural, respectively. 146 posterior EFs (77.25 %) and 8
      posterior EFs (4.25 %) were presented as intrasutural and extrasutural,
      respectively. Although accessory EFs were detected in 25.5 % specimen exhibited
      an extrasutural location. Majority of the EFs (1-4 EFs) were situated on the FS
      line. The mean distances from the FS and the anterior EF, the posterior EF and
      the accessory EF were measured as 2.1 +/- 0.5, 2.0 +/- 1.5 and 2.3 +/- 1.2 mm,
      respectively. The range of the distances from the FS to the anterior EF,
      posterior EF and accessory EF were -1.2 to 3.32 , -1.02 to 5.76 and -1.1 to 3.65
      mm, respectively. CONCLUSION: The ranges of EF changed within 1-6 mm. As the FS
      is not a single point, it is more suitable to make the incision 7 mm above the
      suture line. The data from this study to help the orbital surgeons explain and
      avoid unexpected hemorrhage during the orbital procedures such as posttraumatic
      orbital reconstruction, orbital tumor resections, anterior skull base
      reconstruction, and orbital decompression surgery.

PMID- 25613793
TI  - MRI evaluation of the development of intercondylar notch width in children.
AB  - PURPOSE: The purpose of this study was to evaluate the development of
      intercondylar notch width in children using MRI and assesse the relationship
      between the cruciate ligaments and the width of the intercondylar notch during
      growth. METHODS: We reviewed MRIs and medical records of 76 children (age range
      3.8-16.9) without derangements of the knee. Cases with knee joint instability
      and/or major trauma were excluded. On a standardized coronal image, measurements
      of the width of the intercondylar notch, knee, ACL and PCL were performed using
      image analysis software. The notch width index (NWI), ACL/notch, ACL/knee width,
      PCL/notch, and PCL/knee width were calculated. RESULTS: NWI showed statistical
      correlation with age. The highest values were found in the youngest children, and
      the lowest in the oldest group. While ACL/knee width, and PCL/knee width ratios
      remained proportional over time, the ACL/notch, and PCL/notch ratios increased
      with the age of the patient. CONCLUSION: NWI changes with age and decreases from
      childhood to adolescence. A relative decrease in NWI accounts for an increase in
      the ACL/notch and PCL/notch ratios with age. Studies about NWI in children should
      consider age as a cofactor for analysis.

PMID- 25613794
TI  - Twin anemia-polycythemia sequence after laser surgery for twin-twin transfusion
      syndrome and maternal morbidity.
AB  - Twin anemia-polycythemia sequence (TAPS) is characterized by large inter-twin
      hemoglobin value differences without inter-twin amniotic fluid discordance. The
      management of post-laser TAPS remains controversial. Hence, more studies on TAPS,
      together with the associated maternal complications and outcome of the fetuses
      and infants are needed. Between 2003 and 2012, we performed 287 cases of
      fetoscopic laser photocoagulation for twin-twin transfusion syndrome. Among the
      114 who were placed under our care until delivery, three cases of TAPS occurred.
      In one case, we conducted intrauterine intravenous transfusion, while in the
      other two cases, we adopted expectant management. We performed an emergency
      caesarean section at 27-30 weeks of gestation in all cases due to a severe
      condition of anemia in the TAPS donor. Two cases with antenatal TAPS stage 4 had
      severe maternal complications; one had minute pulmonary embolism, while the other
      had Mirror syndrome. All three pairs of infants survived. One TAPS donor and one
      TAPS recipient had neurodevelopmental impairment; bilateral deafness at 9.5 years
      old and spastic paralysis at 2 years old, respectively. In conclusion, post-laser
      TAPS in a higher stage can cause severe maternal complications. Close
      observations for both fetuses and mothers are required for such cases.

PMID- 25613795
TI  - Synthetic membranes for water purification: status and future.
AB  - Membrane technology offers the best options to "drought proof" mankind on an
      increasingly thirsty planet by purifying seawater or used (waste) water. Although
      desalination by reverse osmosis (RO) and wastewater treatment by membrane
      bioreactors are well established the various membrane technologies still need to
      be significantly improved in terms of separation properties, energy demand and
      costs. We can now define the ideal characteristics of membranes and advances in
      material science and novel chemistries are leading to increasingly effective
      membranes. However developments in membranes must be matched by improved device
      design and membrane engineering. It is likely that limitations in fluid mechanics
      and mass transfer will define the upper bounds of membrane performance.
      Nevertheless major advances and growth over the next 20 years can be anticipated
      with RO remaining as the key to desalination and reclamation, with other membrane
      processes growing in support and in niche areas. 

PMID- 25613796
TI  - Position statement from ADA/AACE/EASD/TES in response to a recently published
      letter to the editor in The Lancet and an editorial addressing the Israeli
      Palestinian fighting in Gaza.

PMID- 25613797
TI  - Optimization-based multicriteria decision analysis for identification of desired
      petroleum-contaminated groundwater remediation strategies.
AB  - The conventional multicriteria decision analysis (MCDA) methods used for
      pollution control generally depend on the data currently available. This could
      limit their real-world applications, especially where the input data (e.g., the
      most cost-effective remediation cost and eventual contaminant concentration)
      might vary by scenario. This study proposes an optimization-based MCDA (OMCDA)
      framework to address such a challenge. It is capable of (1) capturing various
      preferences of decision-makers, (2) screening and analyzing the performance of
      various optimized remediation strategies under changeable scenarios, and (3)
      compromising incongruous decision analysis results. A real-world case study is
      employed for demonstration, where four scenarios are considered with each one
      corresponding to a set of weights representative of the preference of the
      decision-makers. Four criteria are selected, i.e., optimal total pumping rate,
      remediation cost, contaminant concentration, and fitting error. Their values are
      determined through running optimization and optimization-based simulation
      procedures. Four sets of the most desired groundwater remediation strategies are
      identified, implying specific pumping rates under varied scenarios. Results
      indicate that the best action lies in groups 32 and 16 for the 5-year, groups 49
      and 36 for the 10-year, groups 26 and 13 for the 15-year, and groups 47 and 13
      for the 20-year remediation.

PMID- 25613798
TI  - Acute toxicity and sublethal effects of gallic and pelargonic acids on the
      zebrafish Danio rerio.
AB  - Gallic and pelargonic acids are naturally found in a variety of plants and food
      products. Despite their extensive use in man-made applications, little is known
      regarding their potential risks to aquatic vertebrates. The aim of this work was
      to assess the acute toxicity of these polyphenolic and fatty acid compounds to
      the zebrafish. In order to get insights into sublethal effects, the enzyme
      activity of usual biomarkers related to oxidative stress and biotransformation
      were also assessed in fish. These latter included total superoxide dismutase,
      catalase as well as total glutathione peroxidase for antioxidant defence
      mechanisms and glutathione S-transferase for biotransformation related enzyme.
      Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100
      mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L).
      Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in
      fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose
      dependent induction of glutathione peroxidase and glutathione S-transferase was
      reported following gallic acid exposure at the tested concentrations of 10, 20
      and 40 mg/L, with the exception of 100 mg/L of substance where basal activity
      levels were reported. In the case of pelargonic acid, there was no change in
      antioxidant enzyme activity while an inhibition of glutathione S-transferase was
      observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The
      results concerning sublethal effects on biological parameters of zebrafish
      highlighted thereby the need for further investigations following chronic
      exposure to both organic acids. 

PMID- 25613799
TI  - Surface interactions of Cs+ and Co2+ with bentonite.
AB  - Uptake of radioactive metal species from soils and solutions by clay particles
      could be a treatment option due to simplicity of operation and economic cost. In
      this concern, adsorption behavior of Cs+ or Co2+ onto bentonite as a function of
      contact time, pH, initial metal concentration, ionic strength, and temperature
      was studied by batch adsorption technique. Adsorption isotherm data were
      interpreted by Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) isotherm
      models. Bentonite exhibited maximum adsorption capacity of 83.3 mg g-1 for Cs+
      and 15.9 mg g-1 for Co2+. Presence of humic acid (HA) as a representative model
      of organic matter did not significantly affect the adsorption capacity of
      bentonite for Cs+, whereas it increased the adsorption capacity of bentonite for
      Co2+. Thermodynamic parameters, standard enthalpy (DeltaH degrees ), standard
      entropy (DeltaS degrees ), and standard free energy (DeltaG degrees ) were
      determined through batch adsorption experiments performed at four different
      temperatures of 288, 298, 318, and 338 K. Co2+ adsorption onto bentonite showed
      an endothermic reaction (DeltaH degrees  = 13.6 kJ mol-1) whereas Cs+ adsorption
      displayed an exothermic nature (DeltaH degrees  = -4.65 kJ mol-1). Negative
      values of DeltaG degrees  and positive values of DeltaS degrees  indicated the
      feasibility and spontaneous nature of adsorption processes and more disordered
      form after adsorption.

PMID- 25613801
TI  - Exploring factors influencing farmers' willingness to pay (WTP) for a planned
      adaptation programme to address climatic issues in agricultural sectors.
AB  - This study empirically estimates farmers' willingness to pay (WTP) for a planned
      adaptation programme for addressing climate issues in Pakistan's agricultural
      sectors. The contingent valuation method (CVM) was employed to determine a
      monetary valuation of farmers' preferences for a planned adaptation programme by
      ascertaining the value attached to address climatic issues. The survey was
      conducted by distributing structured questionnaires among Pakistani farmers. The
      study found that 67 % of respondents were willing to pay for a planned adaptation
      programme. However, several socioeconomic and motivational factors exert greater
      influence on their willingness to pay (WTP). This paper specifies the steps
      needed for all institutional bodies to better address issues in climate change.
      The outcomes of this paper will support attempts by policy makers to design an
      efficient adaptation framework for mitigating and adapting to the adverse impacts
      of climate change.

PMID- 25613800
TI  - Transcriptional response of stress-regulated genes to industrial effluent
      exposure in the cockle Cerastoderma glaucum.
AB  - This study assessed the responses of molecular biomarkers and heavy metal levels
      in Cerastoderma glaucum exposed for 1 week to two industrial effluents (1%)
      discharged into the Tunisian coastal area, F1 and F2, produced by different units
      of production of a phosphate treatment plant. A significant uptake of metals (Cd,
      Cu, Zn, and Ni) was observed in exposed cockles compared to controls, with an
      uptake higher for F1 than for F2. A decrease in LT50 (stress on stress test) was
      also observed after an exposure to the effluent F1. Treatments resulted in
      different patterns of messenger RNA (mRNA) expression of the different genes
      tested in this report. Gene transcription monitoring performed on seven genes
      potentially involved in the tolerance to metal exposure showed that for both
      exposures, mechanisms are rapidly and synchronically settled down to prevent
      damage to cellular components, by (1) handling and exporting out metal ions
      through the up-regulation of ATP-binding cassette xenobiotic transporter (ABCB1)
      and metallothionein (MT), (2) increasing the mRNA expression of antioxidant
      enzymes (catalase (CAT), superoxide dismutases, CuZnSOD and MnSOD), (3)
      protecting and/or repairing proteins through the expression of heat shock protein
      70 (HSP70) mRNAs, and (4) increasing ATP production (through the up-regulation of
      cytochrome c oxidase 1 (CO1)) to provide energy for cells to tolerate stress
      exposure. The tools developed may be useful both for future control strategies
      and for the use of the cockle C. glaucum as a sentinel species.

PMID- 25613802
TI  - Coal fly ash as a resource for rare earth elements.
AB  - Rare earth elements (REE) have been recognised as critical raw materials, crucial
      for many clean technologies. As the gap between their global demand and supply
      increases, the search for their alternative resources becomes more and more
      important, especially for the countries which depend highly on their import. Coal
      fly ash (CFA), which when not utilised is considered waste, has been regarded as
      the possible source of many elements, including REE. Due to the increase in the
      energy demand, CFA production is expected to grow, making research into the use
      of this material a necessity. As Poland is the second biggest coal consumer in
      the European Union, the authors have studied different coal fly ashes from ten
      Polish power plants for their rare earth element content. All the fly ashes have
      a broadly similar distribution of rear earth elements, with light REE being
      dominant. Most of the samples have REE content relatively high and according to
      Seredin and Dai (Int J Coal Geol 94: 67-93, 2012) classification can be
      considered promising REE raw materials. 

PMID- 25613803
TI  - Inhibition and recovery of biomarkers of earthworm Eisenia fetida after exposure
      to thiacloprid.
AB  - Thiacloprid, a neonicotinoid insecticide, has been used widely in agriculture
      worldwide. In recent years, the adverse effects of neonicotinoid insecticides on
      non-target organisms have attracted more and more attention. In the present
      study, effects of thiacloprid on molecular biomarkers (GST, CarE, CAT, SOD, POD,
      and DNA damage) of earthworm Eisenia fetida were investigated using the
      artificial OECD soil for the first time. Earthworms were exposed to thiacloprid
      (1 and 3 mg/kg) for 7, 14, and 28 days and then transferred to the clean OECD
      soil for 35, 42, and 56 days. Results showed that activities of GST, CarE, CAT,
      SOD, and POD are inhibited following the exposure to thiacloprid at one or more
      sample times and then increased during the recovery course compared with the
      control. Significant DNA damage to E. fetida was also observed by olive tail
      moments in comet assay. These results suggested that thiacloprid could have
      harmful effect on earthworms, and these studied biomarkers might be used in the
      assessment of the risk of thiacloprid to the soil ecosystem environment.

PMID- 25613804
TI  - Pilot-scale study on nitrogen and aromatic compounds removal in printing and
      dyeing wastewater by reinforced hydrolysis-denitrification coupling process and
      its microbial community analysis.
AB  - Aiming to efficiently dispose printing and dyeing wastewater with "high organic
      nitrogen and aromatic compounds, but low carbon source quality", the reinforced
      anaerobic hydrolysis-denitrification coupling process, based on improved UASB
      reactors and segregated collection-disposition strategy, was designed and applied
      at the pilot scale. Results showed that the coupling process displayed efficient
      removal for these two kinds of pollutants (nitrogen and aromatics), since the
      concentration of NH3-N (shortened as rho (NH3-N)) < 8 mg/L, rho (TN) < 15 mg/L
      with long-term stability for the effluent, and both species and abundances of
      aromatics reduced greatly by UASBs according to GC-MS. Microbial community
      analysis by PCR-DGGE showed that Bacteroidetes and Alphaproteobacteria were the
      dominant communities in the bioreactors and some kinds of VFAs-producing,
      denitrifying and aromatic ring opening microorganisms were discovered. Further,
      the nirK and bcrA genes quantification also indicated the coupling process owned
      outstanding denitrification and aromatic compound-degrading potential, which
      demonstrates that the coupling process owns admirable applicability for this kind
      of wastewater treatment.

PMID- 25613805
TI  - Lipid peroxidation and its control in Anguilla anguilla hepatocytes under silica
      coated iron oxide nanoparticles (with or without mercury) exposure.
AB  - Having multidisciplinary applications, iron oxide nanoparticles can inevitably
      enter aquatic system and impact inhabitants such as fish. However, the studies in
      this context have ignored the significance of obvious interaction of iron oxide
      nanoparticles with other persistent co-contaminants such as mercury (Hg) in the
      modulation of the toxicity and underlying mechanisms of iron oxide nanoparticles
      and Hg alone, and concomitant exposures. This study aimed to evaluate lipid
      peroxidation (LPO) and its control with glutathione (GSH) and associated enzymes
      (such as glutathione reductase, GR; glutathione peroxidase, GPX; glutathione
      sulfo-transferase, GST) in European eel (Anguilla anguilla L.) hepatocytes
      exposed to stressors with following schemes: (i) no silica-coated iron oxide
      nanoparticles functionalized with dithiocarbamate (Fe3O4@SiO2/Si DTC, hereafter
      called 'FeNPs'; size range 82 +/- 21 to 100 +/- 30 nm) or Hg, (ii) FeNPs (2.5 MUg
      L(-1)) alone, (iii) Hg (50 MUg L(-1)) alone and (iv) FeNPs + Hg concomitant
      condition during 0 to 72 h. The exhibition of a differential coordination between
      GSH regeneration (determined as GR activity) and GSH metabolism (determined as
      the activity of GPX and GST) was perceptible in A. anguilla hepatocytes in order
      to control FeNPs, Hg and FeNPs + Hg exposure condition-mediated LPO. This study
      revealed the significance of a fine tuning among GR, GPX and GST in keeping LPO
      level under control during FeNPs or Hg alone exposure, and a direct role of total
      GSH (TGSH) in the control of LPO level and impaired GSH metabolism under the
      concomitant (FeNPs + Hg) exposure. An interpretation of the fish risk to FeNPs in
      a multi-pollution state should equally consider the potential outcome of the
      interaction of FeNPs with other contaminants. 

PMID- 25613806
TI  - 203rd ENMC international workshop: respiratory pathophysiology in congenital
      muscle disorders: implications for pro-active care and clinical research 13-15
      December, 2013, Naarden, The Netherlands.

PMID- 25613807
TI  - Abnormal sodium current properties contribute to cardiac electrical and
      contractile dysfunction in a mouse model of myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is the most common neuromuscular disorder and is
      associated with cardiac conduction defects. However, the mechanisms of cardiac
      arrhythmias in DM1 are unknown. We tested the hypothesis that abnormalities in
      the cardiac sodium current (INa) are involved, and used a transgenic mouse model
      reproducing the expression of triplet expansion observed in DM1 (DMSXL mouse).
      The injection of the class-I antiarrhythmic agent flecainide induced prominent
      conduction abnormalities and significantly lowered the radial tissular velocities
      and strain rate in DMSXL mice compared to WT. These abnormalities were more
      pronounced in 8-month-old mice than in 3-month-old mice. Ventricular action
      potentials recorded by standard glass microelectrode technique exhibited a lower
      maximum upstroke velocity [dV/dt](max) in DMSXL. This decreased [dV/dt](max) was
      associated with a 1.7 fold faster inactivation of INa in DMSXL myocytes measured
      by the whole-cell patch-clamp technique. Finally in the DMSXL mouse, no mutation
      in the Scn5a gene was detected and neither cardiac fibrosis nor abnormalities of
      expression of the sodium channel protein were observed. Therefore, alterations in
      the sodium current markedly contributed to electrical conduction block in DM1.
      This result should guide pharmaceutical and clinical research toward better
      therapy for the cardiac arrhythmias associated with DM1.

PMID- 25613808
TI  - Change in physical mobility over 10 years in post-polio syndrome.
AB  - Post-polio syndrome is characterised by progressive muscle weakness and other
      symptoms which can limit physical mobility. We assessed the rate of decline in
      mobility over 10 years in relation to strength decline; and investigated
      potential predictors for the rate of decline of walking capacity, a measure of
      mobility, in 48 patients with post-polio syndrome and proven quadriceps
      dysfunction at baseline. Average walking capacity and self-reported physical
      mobility declined over 10 years, by 6 and 14%, respectively. Concomitantly people
      lost an average of 15% of isometric quadriceps strength. Significantly more
      people used walking aids offering greater support at follow-up. Notably, there
      was much individual variation, with 18% of participants losing a substantial
      amount of walking capacity (27% decline) and concomitant self-reported physical
      mobility (38% decline). Loss of quadriceps strength only explained a small
      proportion of the variance of the decline in walking capacity (R = 11%) and the
      rate of decline could not be predicted from baseline values for strength, walking
      capacity, self-reported physical mobility or basic demographics. The individual
      variability, yet lack of predictive factors, underscores the need for personally
      tailored care based on actual functional decline in patients with post-polio
      syndrome.

PMID- 25613809
TI  - Safety of long-term biologic therapy in rheumatologic patients with a previously
      resolved hepatitis B viral infection.
AB  - European and Asian studies report conflicting data on the risk of hepatitis B
      virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV
      (prHBV) infection undergoing long-term biologic therapies. In this patient
      category, the safety of different immunosuppressive biologic therapies, including
      rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients,
      admitted consecutively as outpatients between 2001 and 2012 and taking biologic
      therapies, underwent evaluation of anti-HCV and HBV markers as well as liver
      amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring
      was performed in patients with a prHBV infection who had started
      immunosuppressive biologic therapy both before and after 2009. Patients were
      considered to have elevated aminotransferase levels if values were >1* upper
      normal limit at least once during follow-up. We found 179 patients with a prHBV
      infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha,
      and 19 with other biologic therapies) and 959 patients without a prHBV infection
      or other liver disease (controls). The mean age in the former group was
      significantly higher than the controls. Patients with a prHBV infection never
      showed detectable HBV DNA serum levels or antibody to hepatitis B surface
      antigen/hepatitis B surface antigen seroreversion. However, when the prevalence
      of elevated amino transferases in patients with prHBV infection was compared to
      controls, it was significantly higher in the former group only for
      aminotransferase levels >1* upper normal limit but not when aminotransferase
      levels >2* upper normal limit were considered. CONCLUSION: Among patients with a
      prHBV infection and rheumatologic indications for long-term biologic therapies,
      HBV reactivation was not seen; this suggests that universal prophylaxis is not
      justified and is not cost-effective in this clinical setting.

PMID- 25613810
TI  - [Paraneoplastic Cushing's syndrome, a real diagnostic and therapeutic challenge:
      A case report and literature review].
AB  - INTRODUCTION: Paraneoplastic Cushing's syndrome is a rare cause of endogenous
      hypercortisolism attributable to ectopic ACTH secretion by non-pituitary tumors.
      Imaging and biochemical results are often inconclusive and differential diagnosis
      with Cushing's disease can then be challenging. Moreover, these tumors may be
      occult and difficult to find and thus the need of new imaging tools such as
      (18)FDG-PET scan and (18)DOPA-PET scan. CASE REPORT: We report a 50-year-old man
      who presented with very aggressive clinical features related to Cushing's
      syndrome. Biological work-up confirmed the hypercortisolism and was consistent
      with an ectopic ACTH secretion. Conventional localization techniques failed to
      show any tumor and bilateral adrenalectomy was performed because of life
      threatening complications. Two years later, thoracic computed tomography reveals
      an 11 mm mass in the left lower pulmonary lobe, (18)FDG-PET scan found a non
      specific mild hypermetabolism of the lung nodule, and the (18)DOPA-PET scan
      confirmed the high uptake of this nodule suggesting an endocrine carcinoma.
      Histology confirmed a typical carcinoid tumor. The tumor cells stained positive
      for ACTH, CD56, chromogranin and synaptophysin. CONCLUSION: This case illustrates
      the dilemma between the need for morphological diagnosis of the ectopic ACTH
      source and control of the life-threatening hypercortisolism. (18)FDG-PET scan and
      (18)DOPA-PET scan should be considered early as a secondary diagnostic tool when
      conventional imagery fails to show any tumor.

PMID- 25613811
TI  - Comparison of the effects of bimatoprost and a fixed combination of latanoprost
      and timolol on 24-hour blood and ocular perfusion pressures: the results of a
      randomized trial.
AB  - BACKGROUND: To compare the effect of bimatoprost and the fixed combination
      latanoprost-timolol (LTFC) on 24-hour systolic (SBP) and diastolic (DBP) blood
      pressure and on 24-hour ocular perfusion pressure (OPP). METHODS: 200 patients
      with glaucoma or ocular hypertension, controlled on the unfixed combination of
      latanoprost and timolol or eligible for dual therapy being not being fully
      controlled on monotherapy were enrolled in a randomized, double-masked, placebo
      controlled, multicentre clinical trial. They were randomized to LTFC (8 a.m.) or
      bimatoprost (8 p.m.) and received 24-hour IOP curve at baseline, 6 and 12 weeks
      (supine and sitting position IOPs were recorded at 8 p.m., midnight, 5 a.m.,
      8a.m., noon and 4 p.m.). Holter 24-hour blood pressure curve was obtained between
      weeks 2 and 12. SBP, DBP, OPP were calculated and compared with ANOVA. Rates of
      diastolic OPP (DPP)<=50, <=40, <=30 mmHg in the 2 groups were calculated and
      compared using Fisher's test. RESULTS: Mean baseline SBP and DBP were 136.5+/
      18.3 vs 134.2+/-20.1 mmHg (p=0.1) and 79.1+/-10.2 vs 78.2+/-10.1 mmHg (p=0.4) in
      the bimatoprost and LTFC groups respectively. Holter SBP was significantly higher
      for bimatoprost (135.1 mmHg vs 128.1 mmHg, p=0.04), while no statistically
      significant difference in DBP was found. DPP was similar in the 2 groups, and
      proportions of patients with at least one value of the 24-hour curve<=50, <=40,
      <=30 mmHg were 94%, 86%, 41% respectively. CONCLUSIONS: Bimatoprost and LTFC had
      similar DBPs and OPPs; SBP was significantly lower with LTFC. In this study, the
      percentage of "dippers" was considerably higher than the one described in
      previous studies on the role of perfusion pressure in glaucoma. TRIAL
      REGISTRATION: NCT02154217, May 21, 2014.

PMID- 25613813
TI  - Label-free impedance detection of cancer cells from whole blood on an integrated
      centrifugal microfluidic platform.
AB  - An electrochemical Lab-on-a-Disc (eLoaD) platform for the automated
      quantification of ovarian cancer cells (SKOV3) from whole blood is reported. This
      centrifugal microfluidic system combines complex sample handling, i.e., blood
      separation and cancer cell extraction from plasma, with specific capture and
      sensitive detection using label-free electrochemical impedance. Flow control is
      facilitated using rotationally actuated valving strategies including siphoning,
      capillary and centrifugo-pneumatic dissolvable-film (DF) valves. For the
      detection systems, the thiol-containing amino acid, L-Cysteine, was self
      assembled onto smooth gold electrodes and functionalized with anti-EpCAM. By
      adjusting the concentration of buffer electrolyte, the thickness of the
      electrical double layer was extended so the interfacial electric field interacts
      with the bound cells. Significant impedance changes were recorded at 117.2 Hz and
      46.5 Hz upon cell capture. Applying AC amplitude of 50 mV at 117.2 Hz and open
      circuit potential, a minimum of 214 captured cells/mm(2) and 87% capture
      efficiency could be recorded. The eLoaD platform can perform five different
      assays in parallel with linear dynamic range between 16,400 and (2.6+/
      0.0003)*10(6) cancer cells/mL of blood, i.e. covering nearly three orders of
      magnitude. Using the electrode area of 15.3 mm(2) and an SKOV3 cell radius of 5
      um, the lower detection limit is equivalent to a fractional surface coverage of
      approximately 2%, thus making eLoaD a highly sensitive and efficient prognostic
      tool that can be developed for clinical settings where ease of handling and
      minimal sample preparation are paramount.

PMID- 25613814
TI  - A novel molecular beacon-based method for isothermal detection of sequence
      specific DNA via T7 RNA polymerase-aided target regeneration.
AB  - Developing molecular beacon (MB)-based method for DNA detection has been of great
      interest to many researchers because of its intrinsic advantages of simplicity,
      rapidity, and specificity. In this work, we have developed a novel MB-based
      method for isothermal detection of sequence-specific DNA via T7 RNA polymerase
      aided target regeneration strategy. The proposed method involves three primary
      processes of target-mediated ligation by T4 DNA ligase, transcription reaction by
      T7 RNA polymerase, and MB switch for signal output. Upon the hybridization with
      DNA target, a rationally designed MB and a pair of primers encoded with T7
      promoter sequence were ligated via the formation of a phosphodiester bond by T4
      DNA ligase. The resultant joint fragment acted as template to initiate T7 RNA
      polymerase-mediated transcription reaction. Correspondingly, a great amount of
      RNA strands complementary to MB and partial primers were transcribed to initiate
      new cyclic reactions of MB switch, ligation, and transcription. With such signal
      amplification strategy of the regeneration of target-like RNA fragments, our
      proposed assay achieved a detection limit as low as ~10 pM, which was ~3 orders
      of magnitude lower than the traditional MB-based method with a recognition
      mechanism in 1:1 stoichiometric ratio between MB and target molecule.

PMID- 25613812
TI  - Increasing the structural coverage of tuberculosis drug targets.
AB  - High-resolution three-dimensional structures of essential Mycobacterium
      tuberculosis (Mtb) proteins provide templates for TB drug design, but are
      available for only a small fraction of the Mtb proteome. Here we evaluate an
      intra-genus "homolog-rescue" strategy to increase the structural information
      available for TB drug discovery by using mycobacterial homologs with conserved
      active sites. Of 179 potential TB drug targets selected for x-ray structure
      determination, only 16 yielded a crystal structure. By adding 1675 homologs from
      nine other mycobacterial species to the pipeline, structures representing an
      additional 52 otherwise intractable targets were solved. To determine whether
      these homolog structures would be useful surrogates in TB drug design, we
      compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM)
      enzyme homologs with experimentally determined structures, using three metrics of
      active site similarity, including superposition of continuous pharmacophoric
      property distributions. Pair-wise structural comparisons revealed that 19/22
      pairs with >55% overall sequence identity had active site Calpha RMSD <1 A, >85%
      side chain identity, and >=80% PSAPF (similarity based on pharmacophoric
      properties) indicating highly conserved active site shape and chemistry. Applying
      these results to the 52 NTM structures described above, 41 shared >55% sequence
      identity with the Mtb target, thus increasing the effective structural coverage
      of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these
      structures in TB drug design can be tested by designing inhibitors using the
      homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb
      cytidylate kinase, is described. The homolog-rescue strategy evaluated here for
      TB is also generalizable to drug targets for other diseases. 

PMID- 25613815
TI  - A near infrared holographic glucose sensor.
AB  - Real-time glucose monitoring has been beneficial in reducing health complications
      associated with diabetes as well as a decrease in mortality. This report
      describes a novel holographic platform, fabricated via laser ablation on chitosan
      hydrogel with gold nanoparticles with a replaying in visible and near IR. The
      sensor responded with a 12 nm and 7 nm shift in wavelength at glucose
      concentrations in the 0-70 mM range and in the visible and near IR, respectively,
      at pH 7.4 and an ionic strength of 154 mM. The sensor did not respond to
      potential interferences found in the interstitial fluid, such as fructose,
      vitamin C and lactate, at their respective normal concentrations and was stable
      to fluctuations in temperature, pH and ionic strength. The characteristics of
      this sensor suggests that it may be applicable for use as an implanted device for
      the real time monitoring of glucose concentrations in the interstitial fluid
      using near IR as the interrogating medium.

PMID- 25613817
TI  - Identification of key genes associated with colorectal cancer based on the
      transcriptional network.
AB  - Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism
      of the cancer is still unclear enough. We aimed to explore the key genes in CRC
      progression. The gene expression profile (GSE4183) of CRC was obtained from Gene
      Expression Omnibus database which included 8 normal samples, 15 adenoma samples,
      15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8
      normal, 15 adenoma, and 15 CRC samples were chosen for our research. The
      differentially expressed genes (DEGs) in normal vs. adenoma, normal vs. CRC, and
      adenoma vs. CRC, were identified using the Wilcoxon test method in R
      respectively. The interactive network of DEGs was constructed to select the
      significant modules using the Pearson's correlation. Meanwhile, transcriptional
      network of DEGs was also constructed using the g: Profiler. Totally, 2,741 DEGs
      in normal vs. adenoma, 1,484 DEGs in normal vs. CRC, and 396 DEGs in adenoma vs.
      CRC were identified. Moreover, function analysis of DEGs in each group showed FcR
      mediated phagocytosis pathway in module 1, cardiac muscle contraction pathway in
      module 6, and Jak-STAT signaling pathway in module 19 were also enriched.
      Furthermore, MZF1 and AP2 were the transcription factor in module 6, with the
      target SP1, while SP1 was also a transcription in module 20. DEGs like NCF1, AKT,
      SP1, AP2, MZF1, and TPM might be used as specific biomarkers in CRC development.
      Therapy targeting on the functions of these key genes might provide novel
      perspective for CRC treatment.

PMID- 25613818
TI  - New member in the Executive Editorial Team.

PMID- 25613820
TI  - Anti-inflammatory and antiatherogenic effects of the NLRP3 inflammasome inhibitor
      arglabin in ApoE2.Ki mice fed a high-fat diet.
AB  - BACKGROUND: This study was designed to evaluate the effect of arglabin on the
      NLRP3 inflammasome inhibition and atherosclerotic lesion in ApoE2Ki mice fed a
      high-fat Western-type diet. METHODS AND RESULTS: Arglabin was purified, and its
      chemical identity was confirmed by mass spectrometry. It inhibited, in a
      concentration-dependent manner, interleukin (IL)-1beta and IL-18, but not IL-6
      and IL-12, production in lipopolysaccharide and cholesterol crystal-activated
      cultured mouse peritoneal macrophages, with a maximum effect at ~50 nmol/L and
      EC50 values for both cytokines of ~ 10 nmol/L. Lipopolysaccharide and cholesterol
      crystals did not induce IL-1beta and IL-18 production in Nlrp3(-/-) macrophages.
      In addition, arglabin activated autophagy as evidenced by the increase in LC3-II
      protein. Intraperitoneal injection of arglabin (2.5 ng/g body weight twice daily
      for 13 weeks) into female ApoE2.Ki mice fed a high-fat diet resulted in a
      decreased IL-1beta plasma level compared with vehicle-treated mice (5.2+/-1.0
      versus 11.7+/-1.1 pg/mL). Surprisingly, arglabin also reduced plasma levels of
      total cholesterol and triglycerides to 41% and 42%, respectively. Moreover,
      arglabin oriented the proinflammatory M1 macrophages into the anti-inflammatory
      M2 phenotype in spleen and arterial lesions. Finally, arglabin treatment markedly
      reduced the median lesion areas in the sinus and whole aorta to 54% (P=0.02) and
      41% (P=0.02), respectively. CONCLUSIONS: Arglabin reduces inflammation and plasma
      lipids, increases autophagy, and orients tissue macrophages into an anti
      inflammatory phenotype in ApoE2.Ki mice fed a high-fat diet. Consequently, a
      marked reduction in atherosclerotic lesions was observed. Thus, arglabin may
      represent a promising new drug to treat inflammation and atherosclerosis.

PMID- 25613819
TI  - The brighter (and evolutionarily older) face of the metabolic syndrome: evidence
      from Trypanosoma cruzi infection in CD-1 mice.
AB  - BACKGROUND: Infection with Trypanosoma cruzi, the protozoan parasite that causes
      Chagas disease, results in chronic infection that leads to cardiomyopathy with
      increased mortality and morbidity in endemic regions. In a companion study, our
      group found that a high-fat diet (HFD) protected mice from T. cruzi-induced
      myocardial damage and significantly reduced post-infection mortality during acute
      T. cruzi infection. METHODS: In the present study metabolic syndrome was induced
      prior to T. cruzi infection by feeding a high fat diet. Also, mice were treated
      with anti-diabetic drug metformin. RESULTS: In the present study, the lethality
      of T. cruzi (Brazil strain) infection in CD-1 mice was reduced from 55% to 20% by
      an 8-week pre-feeding of an HFD to induce obesity and metabolic syndrome. The
      addition of metformin reduced mortality to 3%. CONCLUSIONS: It is an interesting
      observation that both the high fat diet and the metformin, which are known to
      differentially attenuate host metabolism, effectively modified mortality in T.
      cruzi-infected mice. In humans, the metabolic syndrome, as presently construed,
      produces immune activation and metabolic alterations that promote complications
      of obesity and diseases of later life, such as myocardial infarction, stroke,
      diabetes, Alzheimer's disease and cancer. Using an evolutionary approach, we
      hypothesized that for millions of years, the channeling of host resources into
      immune defences starting early in life ameliorated the effects of infectious
      diseases, especially chronic infections, such as tuberculosis and Chagas disease.
      In economically developed countries in recent times, with control of the common
      devastating infections, epidemic obesity and lengthening of lifespan, the
      dwindling benefits of the immune activation in the first half of life have been
      overshadowed by the explosion of the syndrome's negative effects in later life.

PMID- 25613822
TI  - 'Tree-in-bud': thinking beyond infectious causes.
AB  - High-resolution computed tomography is an important diagnostic instrument in
      pneumology. The 'tree-in-bud' sign is a common finding in HRCT scans. The list of
      the most frequent differential diagnoses for 'tree-in-bud' sign includes
      infections with Mycobacterium tuberculosis, nontuberculous mycobacteria, and
      other bacterial, fungal, or viral pathogens. Other causes could be immunological,
      congenital, and idiopathic disorders as well as aspiration or inhalation of toxic
      agents. Rare differential diagnoses are malignant conditions. We present a case
      with 'tree-in-bud' pulmonary infiltrates of chronic lymphatic leukemia which was
      only diagnosed by transbronchial biopsies, and discuss other differential
      diagnoses.

PMID- 25613821
TI  - Distinct expression and localization of the type II diacylglycerol kinase
      isozymes delta, eta and kappa in the mouse reproductive organs.
AB  - BACKGROUND: We have revealed that the type II diacylglycerol kinases (DGKs)
      delta, eta and kappa were expressed in the testis and ovary. However, these
      enzymes' functions in the reproductive organs remain unknown. RESULTS: In this
      study, we first identified the expression sites of type II DGKs in the mouse
      reproductive organs in detail. Reverse transcription-polymerase chain reaction
      and Western blotting confirmed that DGKdelta2 (splicing variant 2) but not
      DGKdelta1 (splicing variant 1) and DGKkappa were expressed in the testis, ovary
      and uterus. DGKeta1 (splicing variant 1) but not DGKeta2 (splicing variant 2) was
      strongly detected in the ovary and uterus. Interestingly, we found that a new
      alternative splicing product of the DGKeta gene, DGKeta3, which lacks exon 26
      encoding 31 amino acid residues, was expressed only in the testis. Moreover, we
      investigated the distribution of type II DGKs in the testis, ovary and uterus
      through in situ hybridization. DGKdelta2 was distributed in the primary
      spermatocytes of the testis and ovarian follicles. DGKeta1 was distributed in the
      oviductal epithelium of the ovary and the luminal epithelium of the uterus.
      Intriguingly, DGKeta3 was strongly expressed in the secondary spermatocytes and
      round spermatids of the testis. DGKkappa was distributed in the primary and
      secondary spermatocyte of the testis. CONCLUSION: These results indicate that the
      expression patterns of the type II DGK isoforms delta2, eta1, eta3 and kappa
      differ from each other, suggesting that these DGK isoforms play specific roles in
      distinct compartments and developmental stages of the reproductive organs,
      especially in the processes of spermatogenesis and oocyte maturation.

PMID- 25613823
TI  - The Kids-Palatable Eating Motives Scale: relation to BMI and binge eating traits.
AB  - INTRODUCTION: Despite high rates of obesity in adolescents, little is known about
      their individual motives for eating caloric foods for reasons unrelated to
      hunger. The goal of this study was to provide a preliminary validation of the
      "Kids Palatable Eating Motives Scale" (K-PEMS), a self-report survey designed to
      identify individual motives for eating tasty foods in adolescents. The study also
      sought to determine if any specific motive(s) can account for variance in BMI and
      binge-eating disorder (BED) traits which can exacerbate obesity. METHODS: BMIz
      and responses to the K-PEMS and the Children's Binge Eating Disorder Scale (C
      BEDS) were obtained from inner-city low-income African American adolescents.
      Linear and logistic regressions were used to identify K-PEMS motives that were
      associated with greater BMIz and binge-eating traits. RESULTS: The K-PEMS
      identified eating tasty foods for Social, Conformity, Reward Enhancement, and
      Coping motives. Higher frequency of eating tasty foods for Social and Conformity
      motives and lower frequency of eating these foods for Reward Enhancement
      accounted for 39% of the variance in BMIz among the overweight and obese
      adolescents. In contrast, eating for Coping motives was related to a 3-fold
      increase in the amended provisional criteria for BED in children which occurred
      in 7% of this young minority sample. DISCUSSION: The K-PEMS can be used to
      identify adolescents' primary motives for eating tasty foods. These motives may
      provide early identification of obesity and binge-eating risk but more
      importantly, can be tailor-targeted to affect specific behavioral and/or
      cognitive changes to prevent these conditions in adulthood.

PMID- 25613824
TI  - Understanding disparity: researchers strive to recruit more African Americans and
      other minorities to studies.

PMID- 25613825
TI  - Cancer screenings still conducted in older patients with limited life expectancy.

PMID- 25613826
TI  - [Twin pregnancy with complete hydatiform mole and coexistent fetus: Report of 4
      cases and review of literature].
AB  - OBJECTIVE: Twin pregnancy with complete hydatiform mole and coexistent fetus is a
      rare clinical condition, occurring in 1 in 22,000 to one in 100,000 pregnancies.
      Continuation of pregnancy in these cases is controversial because of a high risk
      of immediate and long-term maternal morbidity. It allows, however, in 33 % of the
      case the delivery of a healthy child. METHODS: This retrospective study included
      all patients presenting a complete hydatiform mole coexisting with a live twin
      fetus antenatally diagnosed between 2007 and 2012 in the level III maternity of
      the Strasbourg University Hospital. Informations concerning diagnostic
      circumstances, pregnancy follow-up and outcome were studied. RESULTS: Four
      pregnancies were included in the study, all of them were spontaneous. Medical
      termination of pregnancies was related to maternal reasons in the four cases. One
      before 17 weeks of gestation, the three other after 2 weeks of gestation, leading
      to delivery of a healthy child. All patients developed a mild to severe
      preeclampsia. One patient developed a gestational trophoblastic disease,
      requiring chemotherapy by methotrexate. There was no fatal evolution. CONCLUSION:
      Twin pregnancy with complete hydatifom mole and coexistent fetus is associated
      with increased risk of gestational trophoblastic disease. This risk is not
      increased by continuation of pregnancy. In case of prenatal diagnosis of complete
      hydatiform mole coexisting with a live twin fetus, patients should be aware of
      the potential high risk of morbidity and a regular follow-up during and after the
      pregnancy should be intaured. In absence of maternal complications, continuation
      of the pregnancy is possible.

PMID- 25613827
TI  - [Pemphigoid gestationis and Turner syndrome; an uncommon association].
AB  - The authors report an uncommon case of a pregnant woman with Turner syndrome (TS)
      whose pregnancy (with favorable outcome) was complicated by a pemphigoid
      gestationis in third trimester. This case points out that monitoring of these
      pregnancies is not limited to cardiac monitoring. Prevalence of auto-immune
      diseases is increased in the TS. Auto-immune dermatoses, such as pemphigoid
      gestationis, are one of the potential complications during pregnancy and should
      be known to practitioners. 

PMID- 25613828
TI  - Postprandial hyperinsulinaemic hypoglycaemia secondary to a congenital
      portosystemic shunt.
AB  - BACKGROUND: Portosystemic shunts (PSS) are abnormal vascular connections between
      the portal vein or its tributaries and the systemic vein that allow mesenteric
      blood to reach the systemic circulation without first passing through the liver.
      PSS can be associated with various syndromes and can lead to serious
      complications. We report a rare case of a child with PSS and recurrent
      hypoglycaemia. CASE: A 20-month-old girl with Down's syndrome presented with
      recurrent hypoglycaemic episodes. She had multiple anomalies including a
      ventricular septal defect, oesophageal atresia and tracheo-esophageal fistula,
      gastro-oesophageal reflux, and conjugated hyperbilirubinaemia. The initial
      investigations suggested hyperinsulinaemic hypoglycaemia (HH). She did not
      respond to diazoxide. An oral glucose tolerance test suggested postprandial HH.
      Further vascular imaging showed a side-to-side portocaval shunt (Abernethy
      malformation) with relative hypoperfusion of the liver. Hypoglycaemia resolved
      following surgical closure of the portocaval shunt. CONCLUSION: PSS can rarely be
      associated with HH, possibly due to lack of insulin degradation in the liver.
      Surgical closure of the shunt resolves the hypoglycaemia.

PMID- 25613830
TI  - The impact of an emergency department nursing intervention on continuity of care,
      self-care capacities and psychological symptoms: secondary outcomes of a
      randomized controlled trial.
AB  - BACKGROUND: As yet there is no firm evidence about the types of intervention that
      can reduce emergency room revisits. However, the literature on emergency room
      revisits suggests patient difficulties with managing their health problems and
      treatments after discharge may play a role. OBJECTIVES: We carried out a
      randomized trial of an emergency department-based nursing intervention, but
      results showed no reduction in revisits (primary outcome). This paper describes
      the secondary outcomes of the trial: patient perceptions of continuity of care,
      illness perceptions, self-care capacities, psychological symptoms and medication
      adherence 30 days after emergency room discharge. DESIGN: Randomized, controlled
      trial. SETTINGS: The trial was conducted in the emergency department of a
      tertiary cardiac hospital in Montreal, Canada between November 2007 and March
      2010. PARTICIPANTS: The study involved 203 patients, including 108 in the
      experimental group and 95 in the control group. METHODS: The intervention
      included one nurse patient encounter before discharge and two phone calls in the
      10 days after discharge. Participants provided data 30 days post-discharge on
      secondary outcomes potentially related to emergency department revisits. RESULTS:
      Although, as previously reported, the intervention had no impact on the primary
      outcome of emergency department revisits, the present study demonstrated a
      significant positive effect on patients' perceived continuity of care (p=.033),
      self-care capacities (p=.037), anxiety (p=.007) and depressive symptoms (p=.043),
      and the illness perceptions treatment control subscale (p=.037). No differences
      were found for other illness perception subscales or medication adherence (all
      p's>.05). CONCLUSION: Although the intervention did not influence emergency
      department revisits it did improve secondary outcomes, suggesting pathways for
      future research.

PMID- 25613829
TI  - R-modafinil attenuates nicotine-taking and nicotine-seeking behavior in alcohol
      preferring rats.
AB  - (+/-)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and
      has been investigated as a potential medication for the treatment of
      psychostimulant addiction. However, the therapeutic efficacy of (+/-)-MOD for
      addiction is inconclusive. Herein we used animal models of self-administration
      and in vivo microdialysis to study the pharmacological actions of R-modafinil (R
      MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior,
      and mechanisms underlying such actions. We found that R-MOD is more potent and
      effective than S-MOD in attenuating nicotine self-administration in Long-Evans
      rats. As Long-Evans rats did not show a robust reinstatement response to
      nicotine, we used alcohol-preferring rats (P-rats) that display much higher
      reinstatement responses to nicotine than Long-Evans rats. We found that R-MOD
      significantly inhibited intravenous nicotine self-administration, nicotine
      induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior
      in P-rats. R-MOD alone neither sustained self-administration in P-rats previously
      self-administering nicotine nor reinstated extinguished nicotine-seeking
      behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone
      produced a slow-onset moderate increase in extracellular DA. Pretreatment with R
      MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the
      nucleus accumbens (NAc) in both naive and nicotine self-administrating rats,
      suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects.
      In conclusion, the present findings support further investigation of R-MOD for
      treatment of nicotine dependence in humans. 

PMID- 25613832
TI  - Bioimpedance at the bedside: current applications, limitations, and
      opportunities.
AB  - The loss of muscle mass is a defining characteristic of malnutrition, and there
      is ongoing interest in the assessment of lean tissue at the bedside. Globally,
      bioimpedance techniques have been widely appreciated for their noninvasiveness,
      safety, ease of use, portability, and relatively low cost compared with other
      clinically available methods. In this brief update, we review the 3 primary types
      of commercially available bioimpedance devices (single- and multiple-frequency
      and spectroscopy) and differentiate the underlying theory and current
      applications of each. We also address limitations and potential opportunities for
      using these devices at the bedside for clinical assessment. Mixed reports in the
      validation literature for all bioimpedance approaches have raised questions about
      absolute accuracy to estimate whole body composition in clinical populations,
      particularly those with abnormal fluid status and/or body geometry in whom
      underlying method assumptions may be violated. Careful selection of equations can
      improve whole body estimates by single- and multiple-frequency techniques;
      however, not all devices will allow for this approach. Research is increasing on
      the use of bioimpedance variables including phase angle and impedance ratio as
      potential markers of nutrition status and/or clinical outcomes; consensus on
      reference cut-points for interpreting these markers has yet to be established.
      Novel developments in the bioimpedance spectroscopy approach are allowing for
      improved fluid management in individuals receiving dialysis; these developments
      have implications for the clinical management of other conditions associated with
      fluid overload and may also provide enhanced whole body estimates of lean tissue
      through new modeling procedures. 

PMID- 25613833
TI  - The self assembly of proteins; probing patchy protein interactions.
AB  - The ability to control the self-assembly of biological molecules to form defined
      structures, with a high degree of predictability is a central aim for soft matter
      science and synthetic biology. Several examples of this are known for synthetic
      systems, such as anisotropic colloids. However, for biomacromolecules, such as
      proteins, success has been more limited, since aeolotopic (or anisotropic)
      interactions between protein molecules are not easily predicted. We have created
      three double mutants of human gammaD-crystallin for which the phase diagrams for
      singly mutated proteins can be used to predict the behavior of the double
      mutants. These proteins provide a robust mechanism to examine the kinetic and
      thermodynamic properties of proteins in which competing interactions exist due to
      the anisotropic or patchy nature of the protein surface. 

PMID- 25613831
TI  - Griffithsin tandemers: flexible and potent lectin inhibitors of the human
      immunodeficiency virus.
AB  - BACKGROUND: The lectin griffithsin (GRFT) is a potent antiviral agent capable of
      prevention and treatment of infections caused by a number of enveloped viruses
      and is currently under development as an anti-HIV microbicide. In addition to its
      broad antiviral activity, GRFT is stable at high temperature and at a broad pH
      range, displays little toxicity and immunogenicity, and is amenable to large
      scale manufacturing. Native GRFT is a domain-swapped homodimer that binds to
      viral envelope glycoproteins and has displayed mid-picomolar activity in cell
      based anti-HIV assays. Previously, we have engineered and analyzed several
      monomeric forms of this lectin (mGRFT) with anti-HIV EC50 values ranging up to
      323 nM. Based on our previous analysis of mGRFT, we hypothesized that the
      orientation and spacing of the carbohydrate binding domains GRFT were key to its
      antiviral activity. RESULTS: Here we present data on engineered tandem repeats of
      mGRFT (mGRFT tandemers) with antiviral activity at concentrations as low as one
      picomolar in whole-cell anti-HIV assays. mGRFT tandemers were analyzed
      thermodynamically, both individually and in complex with HIV-1 gp120. We also
      demonstrate by dynamic light scattering and cryo-electron microscopy that mGRFT
      tandemers do not aggregate HIV virions. This establishes that, although the intra
      virion crosslinking of HIV envelope glycoproteins is likely integral to their
      activity, the antiviral activity of these lectins is not due to virus aggregation
      caused by inter-virion crosslinking. CONCLUSIONS: The engineered tandemer
      constructs of mGRFT may provide novel and powerful agents for prevention of
      infection by HIV and other enveloped viruses.

PMID- 25613834
TI  - Development and validation of a treatment progress scale for personality
      disordered offenders.
AB  - BACKGROUND: There is a need for a measure to evaluate change in treatment for
      offenders with a personality disorder, and the Progress Rating Scale (PRS) was
      developed to meet this need taking account of multiprofessional input. METHOD:
      The PRS comprises six process and five non-process items developed via thematic
      analysis of routine CPA patient treatment reports at a forensic Personality
      Disorder Service. Rating for items was fully standardized and operationalized
      with revisions aiming to maximize inter-rater agreement reflecting good face and
      content validity. Psychometric properties were examined using PRS ratings for 147
      patients at three different time points in conjunction with relevant
      psychometrics. RESULTS: Following refinement, the instrument demonstrated good
      content validity. Intra-class correlations suggested moderate to substantial
      inter-rater agreement (intraclass correlations: 0.63-0.92). Item analyses
      indicated good internal consistency for process items (Cronbach's alpha: 0.82
      0.88). Correlations with relevant psychometrics revealed meaningful relationships
      between PRS scores, defence styles and social problem solving. PRS score
      trajectories were in line with previously known treatment outcomes supporting
      predictive validity. CONCLUSION: The PRS shows promise as process measure in
      clinical settings but requires further testing on other samples to confirm
      initial findings and demonstrate its utility.

PMID- 25613835
TI  - New coumarin derivative from Euphorbia wallichii.
AB  - One new coumarin derivative (1) and two known compounds, quercetin (2) and
      glyceraldehyde (3) have been isolated from the whole plants of Euphorbia
      wallichii. Their structures were elucidated by means of extensive spectroscopic
      analysis (NMR and ESI-MS) and by comparison with data reported in the literature.
      This is the first isolation of dihydrocoumarin (1) from the genus of Euphorbia. 

PMID- 25613836
TI  - A stretchable nanowire UV-Vis-NIR photodetector with high performance.
AB  - A simple direct-writing technique can be used to fabricate a stretchable UV-vis
      NIR nanowire photodetector (NWPD) consisting of PbS quantum dot (QD)-poly(3
      hexylthiopehene) (P3HT) hybrid NWs. The hybrid NWPD shows superior sensitivity
      and response speed in the UV-vis to NIR range. The stretchable UV-vis-NIR NWPD
      shows a nearly identical photoresponse under extreme (up to 100%) and repeated
      (up to 100 cycles) stretching conditions. 

PMID- 25613837
TI  - Carbon nanotubes part II: a remarkable carrier for drug and gene delivery.
AB  - INTRODUCTION: Carbon nanotubes (CNT) have recently been studied as novel and
      versatile drug and gene delivery vehicles. When CNT are suitably functionalized,
      they can interact with various cell types and are taken up by endocytosis. AREAS
      COVERED: Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT,
      as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal
      compound amphotericin B and the oral administration of erythropoietin have both
      been assisted using CNT. Frequently, targeting moieties such as folic acid,
      epidermal growth factor or various antibodies are attached to the CNT-drug
      nanovehicle. Different kinds of functionalization (e.g., polycations) have been
      used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering
      RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns
      are raised about the nanotoxicology of the CNT and their potentially damaging
      effects on the environment. EXPERT OPINION: CNT-mediated drug delivery has been
      studied for over a decade, and both in vitro and in vivo studies have been
      reported. The future success of CNTs as vectors in vivo and in clinical
      application will depend on achievement of efficacious therapy with minimal
      adverse effects and avoidance of possible toxic and environmentally damaging
      effects.

PMID- 25613839
TI  - Dynamic phases, pinning, and pattern formation for driven dislocation assemblies.
AB  - We examine driven dislocation assemblies and show that they can exhibit a set of
      dynamical phases remarkably similar to those of driven systems with quenched
      disorder such as vortices in superconductors, magnetic domain walls, and charge
      density wave materials. These phases include pinned-jammed, fluctuating, and
      dynamically ordered states, and each produces distinct dislocation patterns as
      well as specific features in the noise fluctuations and transport properties. Our
      work suggests that many of the results established for systems with quenched
      disorder undergoing plastic depinning transitions can be applied to dislocation
      systems, providing a new approach for understanding pattern formation and
      dynamics in these systems. 

PMID- 25613838
TI  - NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for
      fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common form of inherited intellectual
      disability. Previous studies have implicated mGlu5 in the pathogenesis of the
      disease, and many agents that target the underlying pathophysiology of FXS have
      focused on mGluR5 modulation. In the present work, a novel pharmacological
      approach for FXS is investigated. NNZ-2566, a synthetic analog of a naturally
      occurring neurotrophic peptide derived from insulin-like growth factor-1 (IGF-1),
      was administered to fmr1 knockout mice correcting learning and memory deficits,
      abnormal hyperactivity and social interaction, normalizing aberrant dendritic
      spine density, overactive ERK and Akt signaling, and macroorchidism. Altogether,
      our results indicate a unique disease-modifying potential for NNZ-2566 in FXS.
      Most importantly, the present data implicate the IGF-1 molecular pathway in the
      pathogenesis of FXS. A clinical trial is under way to ascertain whether these
      findings translate into clinical effects in FXS patients. 

PMID- 25613840
TI  - Observing implantable collamer lens dislocation by panoramic ultrasound
      biomicroscopy.
AB  - PURPOSE: Observe the image characteristics and dislocation of implantable
      collamer lenses (ICL) following their use to correct high myopia. METHODS: A
      total of 127 patients (242 eyes); 64 females (50.3%) and 63 males (49.7%) were
      included in this retrospective study with ICL V4 implantation and mean spherical
      equivalent -9.08+/-2.04 diopters (D). Panoramic ultrasound biomicroscopy (UBM)
      was utilized to observe anterior segment morphology and ICL location at various
      follow-up periods (1 week preoperative, followed by 1, 3, 6, and yearly
      postoperative). RESULTS: Twenty-eight ICL eyes (11.2%) were noted to have
      abnormal postoperative positioning. The central vault of 12 eyes was too high
      with ICL decentration, mean central vault 1.14+/-0.39 mm; 10 eyes were too low
      but without ICL decentration, mean central vault 0.13+/-0.11 mm. The remaining
      subjects were only ICL decentration without abnormal central vault, mean central
      vault was 0.54+/-0.28 mm. CONCLUSIONS: This study shows the abnormal
      characteristics regarding ICL locations. The ICL dislocation closely correlates
      with the central vault. The ICL dislocation is the primary cause of several
      postoperative complications. Panoramic UBM is one of the most effective imaging
      means to observe the ICL positioning and its stability after implantable surgery.

PMID- 25613841
TI  - Scleral buckling surgery for rhegmatogenous retinal detachment with subretinal
      proliferation.
AB  - PURPOSE: To evaluate the outcome of scleral buckling surgery in patients with
      rhegmatogenous retinal detachment (RRD) with subretinal proliferation. METHODS:
      In this retrospective study, a chart review of all patients with RRD associated
      with subretinal proliferation who were primarily treated with scleral buckling
      procedure, from April 2007 to April 2014, was undertaken. Main outcome measures
      were anatomical retinal reattachment and visual acuity. RESULTS: Forty-four eyes
      of 43 patients including 24 males and 19 females with a mean age of 26.5+/-13.1
      years were evaluated. Immediately after the surgery, retina was reattached in all
      eyes. However, five eyes (11.3%) needed additional surgery for retinal
      redetachment. Single surgery anatomical success rate was 88.7%. Four eyes (9.1%),
      needed pars plana vitrectomy for the treatment of redetachment associated with
      proliferative vitreoretinopathy and scleral buckle revision surgery was
      successfully performed in the other eye. Best corrected visual acuity improved
      from 1.5+/-0.9 logMAR before surgery to 1.1+/-0.7 logMAR after surgery (P<0.001).
      An improvement in BCVA of >2 lines was found in 23 eyes (52.2%) and worsening of
      best corrected visual acuity of >2 lines was observed in 2 eyes (4.5%).
      CONCLUSIONS: Scleral buckling surgery is highly successful in eyes with RRD
      associated with subretinal proliferation.

PMID- 25613842
TI  - Fluorescein angiography and optical coherence tomography in myopic choroidal
      neovascularization.
AB  - PURPOSE: To assess intra/inter-observer agreement, and diagnostic capabilities of
      a color fundus photograph, fundus fluorescein angiography (FFA), and spectral
      domain optical coherence tomography (SD-OCT) in making a diagnosis of myopic
      choroidal neovascularization (CNV). PATIENTS AND METHODS: Two masked observers
      evaluated FFA and SD-OCT images to identify the presence of myopic CNV in 80 high
      myopic eyes of 57 patients. A third masked observer identified CNV on a color
      fundus photo. Presence of myopic CNV on a fundus photo was defined as presence of
      subretinal hemorrhage, thickening of the retina and/or visible membrane at the
      macula. Presence of myopic CNV on FFA was defined as hyperfluorescence in the
      early phase with increase in intensity and size in the late phase; presence of a
      large irregular lesion; and hypofluorsescence due to subretinal hemorrhage.
      Myopic CNV on SD-OCT was defined as the hyper-reflective lesion with or without
      intraretinal fluid or subretinal fluid with retinal thickening. RESULTS:
      Intraobserver repeatability on FFA and SD-OCT was 0.54 and 0.44, respectively.
      Agreement (kappa) between FFA and SD-OCT was 0.38 and 0.3, respectively. Among 34
      eyes, which had the presence of CNV on a color fundus photo, CNV was diagnosed in
      18 (53%) eyes on FFA and in 20 (58.8%) eyes on SD-OCT. Sensitivity and
      specificity of FFA was 47 and 80.4%, respectively, and that of SD-OCT was 58.8
      and 86.9%, respectively. CONCLUSION: Repeatability and reproducibility for
      diagnosis of myopic CNV was better with FFA compared with SD-OCT; however,
      agreement is very poor between FFA and SD-OCT. SD-OCT is comparatively a better
      tool to rule out presence of myopic CNV.

PMID- 25613843
TI  - Rupture of Descemet's membrane secondary to presumed non-accidental injury.

PMID- 25613844
TI  - Outcomes of rectangular 3-snip punctoplasty in acquired punctal stenosis: is
      there a need to be minimally invasive?
AB  - AIM: To report the clinical profiles of acquired punctal stenosis and outcomes
      with rectangular 3-snip punctoplasty. METHODS: Retrospective chart review of all
      patients who underwent rectangular 3-snip punctoplasty, over a 3-year period from
      a single surgeon's (MJA) database was performed. Data retrieved include
      demographics, symptomatology, prior interventions, grades of punctal stenosis,
      associated ocular findings, and outcomes. A minimum follow-up of 6 months
      following punctoplasty was considered for analysis. Success was defined as
      clearance of dye on functional dye disappearance test and resolution of symptoms.
      RESULTS: One hundred and forty five puncta of 87 eyes of 56 patients were
      studied. The mean age at presentations was 52 years. Puncta (71.7%; 104/145) were
      of grade 2 size. Epiphora was the commonest presenting symptom noted in 94.3%
      (82/87) of the eyes. At a minimum follow-up of 6 months, complete resolution of
      symptoms was achieved in 74.7% (65/87) of eyes. Eight out of 87 eyes (9.1%)
      failed to show any improvement secondary to lacrimal obstructions distal to the
      puncta. Five out of 87 (5.7%) eyes showed punctal restenosis whereas 10.3% (9/87)
      of the eyes had functional epiphora post punctoplasty. CONCLUSION: Puncta of
      grade 2 size were the most common in this series. Although rectangular 3-snip
      punctoplasty is an effective and safe procedure for majority of grades 1 and 2 of
      acquired punctal stenosis, a higher percentages of functional epiphora and
      punctal restenosis in the remaining patients should propel further investigations
      into developing nonincisional, minimally invasive alternatives.

PMID- 25613845
TI  - Intra-familial phenotype variability in patients with Jalili syndrome.

PMID- 25613846
TI  - Subthreshold micropulse yellow laser (577 nm) in chronic central serous
      chorioretinopathy: safety profile and treatment outcome.
AB  - PURPOSE: To assess the safety and efficacy of a single session of subthreshold
      micropulse (SM) yellow laser (577 nm) in the treatment of chronic central serous
      chorioretinopathy (CSCR). METHODS: This was a retrospective analysis of 15 eyes
      of 13 patients with CSCR of >3 months duration who had been treated with SM
      yellow laser (577 nm). All patients had been treated using multiple spots of
      laser with a duty cycle of 10% over areas of focal and diffuse leak, as seen on
      fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).
      Reduction in subretinal fluid height on spectral domain optical coherence
      tomography (SD-OCT) was used to measure the response to treatment. RESULTS: The
      mean follow-up was at 8 weeks (4-19 weeks). All eyes responded to treatment. The
      mean subretinal fluid height pre and post treatment was 232 and 49 MUm,
      respectively, showing a 79% average reduction (P<0.001) in fluid height. There
      was no evidence of retinal pigment epithelium or retinal damage on SD-OCT, FFA,
      or fundus autofluorescence. Median visual improvement was one line on Snellen's
      visual acuity chart (P=0.015). Microperimetry was performed in eight eyes of
      which six eyes (75%) showed an improvement in the threshold values post
      treatment. CONCLUSION: SM yellow laser is an effective treatment option for
      chronic CSCR.

PMID- 25613847
TI  - Evaluation of retinopathy of prematurity screening in reverse Kangaroo Mother
      Care: a pilot study.
AB  - PURPOSE: To evaluate retinopathy of prematurity (ROP) screening practice in
      reverse Kangaroo Mother Care (R-KMC) with respect to stress and pain to the
      infant. METHODS: In a pilot study we evaluated ROP screening practice in R-KMC in
      20 babies at risk of ROP. The R-KMC differed from the conventional KMC with
      respect to the baby position where the baby lay supine on mother's chest. With
      the mother lying supine and the baby in R-KMC position, screening examinations
      were done with indirect ophthalmoscope. The outcome measures included stress
      (quantified by pulse, respiration, and oxygen saturation) and pain to the baby by
      observing facial expression (eye squeezing, crying, and brow bulge). The heart
      rate, respiratory rate, and SpO2 (%) were compared before and immediately after
      the procedure using paired t-test. RESULT: Mean (+/-SD) gestational age and birth
      weight were 30.8+/-2.3 weeks and 1362.5+/-253.9 g, respectively. During
      examination in R- KMC position 8 babies (40%) were completely relaxed (no eye
      squeezing and crying), 10 (50%) were partially relaxed (no brow bulge) and 2
      babies (10%) were not relaxed. A change in heart and respiration rate both by 10
      per minute was recorded in 12 (60%) and 10 (50%) babies, respectively. Five
      babies (25%) had reduction in blood oxygen concentration below 92%. The majority
      of the mothers (19 of 20) were relaxed. CONCLUSION: ROP screening in R-KMC can be
      a baby friendly screening practice with respect to stress and pain to the infant
      and needs further evaluation in a larger cohort.

PMID- 25613848
TI  - The incidence, embryology, and oculofacial abnormalities associated with eyelid
      colobomas.
AB  - PURPOSE: To describe a cohort of patients with congenital eyelid coloboma, to
      identify associated ocular and craniofacial abnormalities, and to establish any
      correlation between the size and location of eyelid colobomas and the presence of
      such abnormalities. METHODS: An observational case series of 55 patients with
      eyelid coloboma treated by a single surgeon (JROC) between 1985 and 2005.
      RESULTS: Eyelid colobomas predominantly affected the upper lids (93%), and were
      typically unilateral (76%). About a third (29%) were an isolated finding, with
      the remainder associated with other ocular (62%) and/or craniofacial (53%)
      abnormalities. Of those with ocular abnormalities; 19 (56%) had conjunctival
      traction bands, 16 (47%) choristomas, and 8 (24%) an abnormal globe. Of those
      with craniofacial abnormalities; 13 (45%) had Goldenhar Syndrome, 10 (35%)
      clefting disorders, and 4 (14%) Fraser Syndrome. Clefting disorders were
      typically associated with more severe colobomas and a higher incidence of
      conjunctival traction bands, first arch syndromes with smaller colobomas and more
      choristomas. Overall large colobomas were significantly associated with the
      presence of other craniofacial defects compared with small colobomas (P<0.01,
      chi(2)), but coloboma size did not correspond with the presence of other ocular
      abnormalities. CONCLUSIONS: Coloboma size, location, and associations in this
      series are consistent with our current understanding of eyelid embryogenesis. It
      is likely that those colobomas associated with other craniofacial and ocular
      abnormalities are those which result from errors earlier in embryogenesis during
      eyelid specification, growth, and closure, whereas isolated colobomas arise later
      during eyelid separation, and after codependent structures have developed.

PMID- 25613849
TI  - Minimal incision posterior approach levator plication for aponeurotic ptosis.
AB  - PURPOSE: To assess the efficacy and predictability of a minimal incision
      posterior approach levator plication technique for correction of involutional
      ptosis. METHOD: Retrospective chart review of patients with involutional
      aponeurotic ptosis underwent minimal incision posterior approach levator
      plication technique between August 2013 and June 2014 by a single surgeon. The
      upper lid was double everted, and the conjunctiva and Muller's muscle layers were
      incised vertically until the levator aponeurosis could be identified. The
      incision(s) was similar to performing incision and curettage of chalazion, except
      that the site was above the tarsal plate and extended towards the fornix. Then
      insertion of aponeurosis was dissected away from the anterior tarsal surface, and
      the more superiorly located levator was plicated on it with double arm suture(s).
      No tissue was excised in this procedure. Surgical success was defined as a
      postoperative margin reflex distance (MRD)>2 mm and<4.5 mm, interlid height<1 mm
      and satisfactory contour. RESULTS: Forty-four lids of 27 patients were included.
      Preoperative mean MRD was 0.48 +/- 0.56 mm. Severe ptosis of MRD<1 mm was present
      in 34/44 patients (77.3%). The postoperative mean MRD was 2.49 +/- 0.53 mm, and
      mean improvement was 2.02 +/- 0.61 mm, which was statistically significant
      (P<0.001). The overall success rate was 38/44 (86.4%). CONCLUSIONS: Minimal
      incision posterior approach to levator plication was effective for the correction
      of aponeurotic ptosis with moderate to good levator function.

PMID- 25613850
TI  - Anti-virulence potential of eugenyl acetate against pathogenic bacteria of
      medical importance.
AB  - Considering the role of virulence factors in bacterial pathogenicity, interfering
      with the virulence factor production could afford a novel way for the treatment
      of infections caused by pathogenic bacteria. In the present study, an effect of
      eugenyl acetate (EA), a well-known phytochemical from Syzygium aromaticum (clove
      bud) was assessed for its anti-virulence potential against both Gram-negative and
      Gram-positive pathogens. Eugenyl acetate at 150 ug/ml, significantly inhibited
      virulence factor production such as pyocyanin and pyoverdin by Pseudomonas
      aeruginosa ATCC 27853 up to 9.4 (P < 0.01) and 3.7 fold (P < 0.01), respectively.
      In addition, protease activity of P. aeruginosa was significantly reduced upon
      treatment with EA (P < 0.05). The test compound (150 ug/ml) lowered haemolytic
      activity of Staphylococcus aureus ATCC 29213 up to tenfold (P < 0.01).
      Furthermore, a decrease in staphyloxanthin pigment production was observed when
      S. aureus cells were treated with increasing concentrations of EA (37.5-150
      ug/ml). The test compound at 75 ug/ml exhibited quorum sensing inhibitory
      potential in inhibiting violacein production by Chromobacterium violaceum DMST
      21761 up to 27.7 fold (P < 0.01). Thus, results of the present work reveal the
      potential of EA as an alternative candidate to control pathogenicity of both Gram
      negative and Gram-positive organisms. 

PMID- 25613851
TI  - Erratum to: Pedobacter bambusae sp. nov., isolated from soil of a bamboo
      plantation.

PMID- 25613852
TI  - Pedobacter lotistagni sp. nov. isolated from lotus pond water.
AB  - A light-yellow coloured, Gram-stain negative, rod-shaped, aerobic, non-motile
      bacterium, designated THG-DN6.8(T), was isolated from a lotus pond near Donghaksa
      temple in Daejeon, South Korea. The strain was found to grow well on nutrient
      agar, optimally at pH 6.0-7.5, at temperature 25-28  degrees C and in the
      presence of 0.5 % NaCl. Based on 16S rRNA gene sequence analysis, strain THG
      DN6.8(T) was found to share the highest sequence similarity with Pedobacter
      koreensis KCTC 12536(T), followed by Pedobacter glacialis CCTCC AB 2012941(T),
      Pedobacter kyungheensis KACC 16221(T), Pedobacter caeni LMG 22862(T), Pedobacter
      insulae KCTC 12820(T) and Pedobacter boryungensis KCTC 23344 (T). The DNA G+C
      content was determined to be 36.8 mol%. In DNA-DNA hybridization tests, the DNA
      relatedness between strain THG-DN6.8(T) and its closest phylogenetic neighbour P.
      koreensis was found to be below 10 %. The predominant isoprenoid quinone was
      identified as menaquinone MK-7 and the major polar lipid as
      phosphatidylethanolamine. The major fatty acids of strain THG-DN6.8(T) were
      identified as iso-C15:0, C16:0, C18:0 and C16:1 omega6c and/or C16:1 omega7c
      (summed feature 3). On the basis of the phenotypic characteristics, genotypic
      analysis and chemotaxonomic characteristics, strain THG-DN6.8(T) is considered to
      represent a novel species of the genus Pedobacter, for which the name Pedobacter
      lotistagni sp. nov. is proposed. The type strain is THG-DN6.8(T) (= KCTC 42229(T)
      = JCM 30354(T)). 

PMID- 25613853
TI  - The effects of the NintendoTM Wii Fit on gait, balance, and quality of life in
      individuals with incomplete spinal cord injury.
AB  - PURPOSE: To assess the effects of virtual reality using the NintendoTM Wii Fit on
      balance, gait, and quality of life in ambulatory individuals with incomplete
      spinal cord injury (iSCI). RELEVANCE: There is a need for continued research to
      support effective treatment techniques in individuals with iSCI to maximize each
      individual's potential functional performance. SUBJECTS: Five males with a mean
      age of 58.6 years who had an iSCI and were greater than one-year post injury.
      METHODS: An interrupted time series design with three pre-tests over three weeks,
      a post-test within one week of the intervention, and a four-week follow up.
      Outcome measures: gait speed, timed up and go (TUG), forward functional reach
      test (FFRT) and lateral functional reach test (LFRT), RAND SF-36. Intervention
      consisted of one-hour sessions with varied games using the Nintendo Wii Fit twice
      per week for seven weeks. Survey data was also collected at post-test. Results
      There were statistically significant changes found in gait speed and functional
      reach. The changes were also maintained at the four-week follow up post-test.
      Survey reports suggested improvements in balance, endurance, and mobility with
      daily tasks at home. CONCLUSION: All subjects who participated in training with
      the NintendoTM Wii Fit demonstrated statistically significant improvements in
      gait speed and functional reach after seven weeks of training. Given the
      potential positive impact that the NintendoTM Wii Fit has on functional reach and
      gait speed in patients with iSCI, physical therapists may want to incorporate
      these activities as part of a rehabilitation program.

PMID- 25613854
TI  - Effects of different electron donor feeding patterns on TCE reductive
      dechlorination performance.
AB  - This study investigates how the feeding pattern of e(-) donors might affect the
      efficiency of enhanced in situ bioremediation in TCE-contaminated aquifers. A
      series of lab-scale batch experiments were conducted using butyrate or hydrogen
      gas (H2) as e(-) donor and a TCE-dechlorinating microbial consortium dominated by
      Dehalococcoides spp. The results of these experiments demonstrate that butyrate
      is similarly efficient for TCE dechlorination whether it is injected once or in
      doses. Moreover, the present work indicates that the addition of butyrate in
      great excess cannot be avoided, since it most likely provide, even indirectly,
      significant part of the H2 required. Furthermore, methanogenesis appears to be
      the major ultimate e(-) accepting process in all experiments, regardless the e(-)
      donor used and the feeding pattern. Finally, the timing of injection of H2 seems
      to significantly affect dechlorination performance, since the injection during
      the early stages improves VC-to-ETH dechlorination and reduce methanogenic
      activity.

PMID- 25613855
TI  - Effects of metal-soil contact time on the extraction of mercury from soils.
AB  - To investigate the mercury aging process in soils, soil samples were spiked with
      inorganic mercury (Hg(II)) or methylated mercury (MeHg) and incubated for 2, 7,
      14 or 28 days in the laboratory. Potential availability of mercury, assessed by
      bovine serum albumin (BSA) or calcium chloride (CaCl2) extraction, decreased by 2
      19 times for Hg(II) or 2-6 times for MeHg, when the contact time increased from 2
      to 28 days. Decreased Hg(II) extraction could be explained by Hg(II) geochemical
      fractionation, i.e., Hg(II) migrated from more mobile fractions (water soluble
      and stomach acid soluble fractions) to refractory ones (organo-complexed,
      strongly complexed and residual fractions) over time, resulting in more stable
      association of Hg(II) with soils. In addition, decrease of mercury extraction was
      more evident in soils with lower organic content in most treatments, suggesting
      that organic matter may potentially play an important role in mercury aging
      process. In view of the significant decreased Hg(II) or MeHg extraction with
      prolonged contact time, mercury aging process should be taken into account when
      assessing risk of mercury in contaminated soils.

PMID- 25613856
TI  - Phenotyping nematode feeding sites: three-dimensional reconstruction and
      volumetric measurements of giant cells induced by root-knot nematodes in
      Arabidopsis.
AB  - The control of plant parasitic nematodes is an increasing problem. A key process
      during the infection is the induction of specialized nourishing cells, called
      giant cells (GCs), in roots. Understanding the function of genes required for GC
      development is crucial to identify targets for new control strategies. We propose
      a standardized method for GC phenotyping in different plant genotypes, like those
      with modified genes essential for GC development. The method combines images
      obtained by bright-field microscopy from the complete serial sectioning of galls
      with TrakEM2, specialized three-dimensional (3D) reconstruction software for
      biological structures. The volumes and shapes from 162 3D models of individual
      GCs induced by Meloidogyne javanica in Arabidopsis were analyzed for the first
      time along their life cycle. A high correlation between the combined volume of
      all GCs within a gall and the total area occupied by all the GCs in the section/s
      where they show maximum expansion, and a proof of concept from two Arabidopsis
      transgenic lines (J0121 ? DTA and J0121 ? GFP) demonstrate the reliability of the
      method. We phenotyped GCs and developed a reliable simplified method based on a
      two-dimensional (2D) parameter for comparison of GCs from different Arabidopsis
      genotypes, which is also applicable to galls from different plant species and in
      different growing conditions, as thickness/transparency is not a restriction. 

PMID- 25613857
TI  - Risk of lens cloudiness during colorectal endoscopic submucosal dissection and
      ability of a novel lens cleaner to maintain and restore endoscopic view.
AB  - BACKGROUND AND AIM: Generally, colorectal endoscopic submucosal dissection (ESD)
      cannot be carried out with severe lens cloudiness. We examined the occurrence of
      lens cloudiness during ESD as well as the efficacy of a novel cleaner for it.
      METHODS: This study was a prospective study compared to historical control.
      First, we analyzed 103 ESD cases using standard cleaner at the Kyoto Prefectural
      University of Medicine in 2012. Relationship between lens cloudiness and clinical
      characteristics of lesions was analyzed. Lens cloudiness was recorded as grade 0
      (clear) to grade 2 (very unclear). Then, we recruited 92 consecutive patients who
      underwent colorectal ESD using the novel cleaner from August 2013 to July 2014.
      The cleaner was applied on top of the lens before procedure and ability to
      prevent lens cloudiness was tested. Additionally, the novel cleaner was injected
      from endoscopic channel into a space created by endoscopic hood and colonic wall
      in seven cases with grade 1 or 2 of lens cloudiness and the ability to clean lens
      cloudiness inside the colon was tested. RESULTS: Rate of severe lens cloudiness
      was 8.7%. Multivariate analysis showed that severe lens cloudiness was related
      with severe submucosal fatty tissue (P < 0.001). The novel cleaner had
      significantly less cloudiness cases compared to the standard cleaner (14.1% vs
      33.0%, P = 0.002). Additionally, the novel cleaner enabled us to clean lens
      cloudiness in all seven cases. CONCLUSION: Lens cloudiness during ESD was
      associated with submucosal fatty tissue. Effective lens cleaner should be used to
      prevent and clean lens cloudiness.

PMID- 25613858
TI  - Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1
      c][1,2,4]triazin-6-amines.
AB  - A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine
      derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4
      triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All
      synthesized compounds were tested against HL60 (human promyelocytic leukemia),
      MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma)
      cell lines, as cytotoxic agents. The structure-activity relationships study
      revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl
      ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl
      derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and
      6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 -
      20.4 MUM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2
      yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4
      cell line (IC50 values 12.1 and 13.0 MUM, respectively). Also, the acridine
      orange/ethidium bromide staining assay in MCF-7 cells suggested that the
      cytotoxic activity of compound 6r occurs via apoptosis.

PMID- 25613859
TI  - One-step synthesis of azole- and benzazole-based sulfonamides in aqueous media.
AB  - Several benzazoles (benzoxazoles, benzothiazoles, and benzimidazoles) and azoles
      (1H-1,2,4-triazole-5(4H)-thiones and 1,2,4-oxadiazoles) bearing a sulfonamide
      moiety were efficiently prepared via the reactions of dimethyl (arylsulfonyl)
      dithioimidocarbonate derivatives and their 2-aminobenzene precursors,
      thiosemicarbazides, and amidoximes, respectively, in the presence of K(2)CO(3) as
      a base in aqueous ethanol (25%) as a green media in moderate to excellent yields.

PMID- 25613860
TI  - No evidence of human herpesvirus DNA in the CSF of multiple sclerosis patients.

PMID- 25613861
TI  - Lack of evidence for an association between the V393A variant of COQ2 and
      amyotrophic lateral sclerosis in a Han Chinese population.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive disorder involving the
      degeneration of motor neurons. ALS shares pathogenic characteristics and genetic
      risk factors with multiple system atrophy (MSA). Here we examine whether a
      variant of the COQ2 gene associated with MSA in Japanese is also associated with
      ALS in Han Chinese. The ligase detection reaction was used to measure the
      frequency of the V393A variant of COQ2 in 282 patients with ALS and 491 healthy
      controls. The ALS and control groups showed no significant differences in
      genotype frequencies (OR 1.298, 95 %CI 0.396-4.253, p = 0.666) or allele
      frequencies (OR 1.314, 95 %CI 0.403-4.286, p = 0.650) at the V393A locus of COQ2.
      We also conducted a meta-analysis and combined our data with the previous
      Japanese research, but still failed to detect an association between V393A and
      ALS. In conclusion, This case-control study shows no evidence for an association
      between ALS and the V393A variant of COQ2 in Han Chinese and together with the
      Japanese research suggests that this polymorphism may not be linked to the risk
      of ALS in East Asians in general.

PMID- 25613862
TI  - Vestibular examinations in apogeotropic positional nystagmus caused by cerebellar
      tumor.

PMID- 25613863
TI  - Kinetic analysis of the weak affinity interaction between tris and lysozyme.
AB  - The biosensor based on total internal reflection imaging ellipsometry (TIRIE),
      regarded as an automotive real-time research approach for biomolecular
      interaction, is introduced to analyze the kinetic process of the weak interaction
      between tris and lysozyme. The experiment is performed by delivering lysozyme
      solution diluted to different concentrations to the biosensor substrate interface
      immobilized with tris. By applying pseudo-first-order interaction kinetics model,
      we are able to obtain the kinetic parameters from fitting experimental data. The
      calculated association rate constant and dissociation rate constant of tris and
      lysozyme interaction are in 10(-2) mol(-1) s(-1) and 10(3)s(-1) magnitude,
      respectively. To further improve TIRIE's ability for kinetically characterizing
      biomolecular interaction, a theoretical method to deduce associate rate constant
      before experiment is proposed.

PMID- 25613864
TI  - Prolonging the survival of Tsc2 conditional knockout mice by glutamine
      supplementation.
AB  - The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant
      disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2
      (tuberin), which serve as negative regulators of mechanistic target of rapamycin
      complex 1 (mTORC1) activity. TSC patients exhibit developmental brain
      abnormalities and tuber formations that are associated with neuropsychological
      and neurocognitive impairments, seizures and premature death. Mechanistically,
      TSC1 and TSC2 loss of function mutations result in abnormally high mTORC1
      activity. Thus, the development of a strategy to inhibit abnormally high mTORC1
      activity may have therapeutic value in the treatment of TSC. mTORC1 is a master
      regulator of growth processes, and its activity can be reduced by withdrawal of
      growth factors, decreased energy availability, and by the immunosuppressant
      rapamycin. Recently, glutamine has been shown to alter mTORC1 activity in a TSC1
      TSC2 independent manner in cells cultured under amino acid- and serum-deprived
      conditions. Since starvation culture conditions are not physiologically relevant,
      we examined if glutamine can regulate mTORC1 in non-deprived cells and in a
      murine model of TSC. Our results show that glutamine can reduce phosphorylation
      of S6 and S6 kinase, surrogate indicators of mTORC1 activity, in both deprived
      and non-deprived cells, although higher concentrations were required for non
      deprived cultures. When administered orally to TSC2 knockout mice, glutamine
      reduced S6 phosphorylation in the brain and significantly prolonged their
      lifespan. Taken together, these results suggest that glutamine supplementation
      can be used as a potential treatment for TSC. 

PMID- 25613865
TI  - BcGs1, a glycoprotein from Botrytis cinerea, elicits defence response and
      improves disease resistance in host plants.
AB  - In this study, a necrosis-inducing protein was purified from the culture filtrate
      of the necrotrophic fungus Botrytis cinerea BC-98 strain. Secreted proteins were
      collected and fractionated by liquid chromatography. The fraction with the
      highest necrosis-inducing activity was further purified. A glycoprotein named
      BcGs1 was identified by 2D electrophoresis and mass spectrometry. The BcGs1
      protein consisted of 672 amino acids with a theoretical molecular weight of
      70.487 kDa. Functional domain analysis indicated that BcGs1 was a glucan 1,4
      alpha-glucosidase, a cell wall-degrading enzyme, with a Glyco_hydro_15 domain and
      a CBM20_glucoamylase domain. The BcGs1 protein caused necrotic lesions that
      mimicked a typical hypersensitive response and H2O2 production in tomato and
      tobacco leaves. BcGs1-treated plants exhibited resistance to B. cinerea,
      Pseudomonas syringae pv. tomato DC3000 and tobacco mosaic virus in systemic
      leaves. In addition, BcGs1 triggered elevation of the transcript levels of the
      defence-related genes PR-1a, TPK1b and Prosystemin. This is the first report of a
      Botrytis glucan 1,4-alpha-glucosidase triggering host plant immunity as an
      elicitor. These results lay a foundation for further study of the comprehensive
      interaction between plants and necrotrophic fungi.

PMID- 25613866
TI  - Electronic cigarettes and cannabis: an exploratory study.
AB  - AIMS: To describe cannabis 'vaping' with electronic cigarettes (e-cigarettes) or
      electronic vaporizers (e-vaporizers). METHODS: Internet survey in 2013-2014.
      Participants were 11 people who 'vaped' cannabis with e-cigarettes and 44 people
      who vaped cannabis with e-vaporizers, enrolled online. RESULTS: Most participants
      were men (78%). They had used e-cigarettes for 6 days and e-vaporizers for 50
      days on average to vape cannabis. Current users of e-cigarettes vaped cannabis on
      2 days/week versus 6 days/week for users of e-vaporizers. In these devices, they
      mostly inserted cannabis buds and oil rather than hashish or wax/butane honey
      oil. Dual users, who both smoked and vaped cannabis, currently smoked 5
      joints/week compared to 14 joints/week before they started to vape cannabis (p =
      0.004). Half the participants (45%) reported that vaping cannabis helped them
      stop or reduce their total cannabis use, 37% that it had no impact on their
      cannabis use, and 6% that it increased it. Vaping cannabis was perceived as
      healthier and more discrete than smoking it (less odor). Disadvantages included
      dry mouth and fewer positive cannabis effects. CONCLUSIONS: Cannabis vaping via e
      cigarettes or e-vaporizers is an infrequent behavior that was previously almost
      undocumented. E-cigarettes do not appear to be a very appealing way to use
      cannabis.

PMID- 25613867
TI  - Rethink the Nicaragua Canal.

PMID- 25613869
TI  - Planetary science. Comet close-up reveals a world of surprises.

PMID- 25613870
TI  - Demography. Surveys reveal state of Afghan population.

PMID- 25613871
TI  - Nuclear power. Japan's nuclear renaissance dogged by waste challenge.

PMID- 25613872
TI  - Biology. Malaria may accelerate aging in birds.

PMID- 25613873
TI  - Probing the proton.

PMID- 25613874
TI  - The insurgent.

PMID- 25613875
TI  - Planetary science. Play it again, SAM.

PMID- 25613876
TI  - Immunology. Flexibility for specificity.

PMID- 25613877
TI  - Infectious diseases. Understanding artemisinin resistance.

PMID- 25613878
TI  - Public health. Smoke and fire over e-cigarettes.

PMID- 25613879
TI  - Environment and development. Brazil's Soy Moratorium.

PMID- 25613880
TI  - Carnivore coexistence: value the wilderness.

PMID- 25613881
TI  - Carnivore coexistence: America's recovery.

PMID- 25613882
TI  - Carnivore coexistence: trophic cascades.

PMID- 25613883
TI  - Ferns to fulfillment.

PMID- 25613884
TI  - Catching a comet. Rosetta begins its comet tale. Introduction.

PMID- 25613885
TI  - Human evolution. Human-like hand use in Australopithecus africanus.
AB  - The distinctly human ability for forceful precision and power "squeeze" gripping
      is linked to two key evolutionary transitions in hand use: a reduction in
      arboreal climbing and the manufacture and use of tools. However, it is unclear
      when these locomotory and manipulative transitions occurred. Here we show that
      Australopithecus africanus (~3 to 2 million years ago) and several Pleistocene
      hominins, traditionally considered not to have engaged in habitual tool
      manufacture, have a human-like trabecular bone pattern in the metacarpals
      consistent with forceful opposition of the thumb and fingers typically adopted
      during tool use. These results support archaeological evidence for stone tool use
      in australopiths and provide morphological evidence that Pliocene hominins
      achieved human-like hand postures much earlier and more frequently than
      previously considered. 

PMID- 25613887
TI  - Planetary science. Shock compression of stishovite and melting of silica at
      planetary interior conditions.
AB  - Deep inside planets, extreme density, pressure, and temperature strongly modify
      the properties of the constituent materials. In particular, how much heat solids
      can sustain before melting under pressure is key to determining a planet's
      internal structure and evolution. We report laser-driven shock experiments on
      fused silica, alpha-quartz, and stishovite yielding equation-of-state and
      electronic conductivity data at unprecedented conditions and showing that the
      melting temperature of SiO2 rises to 8300 K at a pressure of 500 gigapascals,
      comparable to the core-mantle boundary conditions for a 5-Earth mass super-Earth.
      We show that mantle silicates and core metal have comparable melting temperatures
      above 500 to 700 gigapascals, which could favor long-lived magma oceans for large
      terrestrial planets with implications for planetary magnetic-field generation in
      silicate magma layers deep inside such planets. 

PMID- 25613888
TI  - Magnetic materials. Tilt engineering of spontaneous polarization and
      magnetization above 300 K in a bulk layered perovskite.
AB  - Crystalline materials that combine electrical polarization and magnetization
      could be advantageous in applications such as information storage, but these
      properties are usually considered to have incompatible chemical bonding and
      electronic requirements. Recent theoretical work on perovskite materials
      suggested a route for combining both properties. We used crystal chemistry to
      engineer specific atomic displacements in a layered perovskite, (Ca(y)Sr(1-
      y))(1.15)Tb(1.85)Fe2O7, that change its symmetry and simultaneously generate
      electrical polarization and magnetization above room temperature. The two
      resulting properties are magnetoelectrically coupled as they arise from the same
      displacements.

PMID- 25613889
TI  - Chronic infection. Hidden costs of infection: chronic malaria accelerates
      telomere degradation and senescence in wild birds.
AB  - Recovery from infection is not always complete, and mild chronic infection may
      persist. Although the direct costs of such infections are apparently small, the
      potential for any long-term effects on Darwinian fitness is poorly understood. In
      a wild population of great reed warblers, we found that low-level chronic malaria
      infection reduced life span as well as the lifetime number and quality of
      offspring. These delayed fitness effects of malaria appear to be mediated by
      telomere degradation, a result supported by controlled infection experiments on
      birds in captivity. The results of this study imply that chronic infection may be
      causing a series of small adverse effects that accumulate and eventually impair
      phenotypic quality and Darwinian fitness. 

PMID- 25613886
TI  - Astrophysics. The exceptionally powerful TeV gamma-ray emitters in the Large
      Magellanic Cloud.
AB  - The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been
      observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of
      100 billion electron volts for a deep exposure of 210 hours. Three sources of
      different types were detected: the pulsar wind nebula of the most energetic
      pulsar known, N 157B; the radio-loud supernova remnant N 132D; and the largest
      nonthermal x-ray shell, the superbubble 30 Dor C. The unique object SN 1987A is,
      unexpectedly, not detected, which constrains the theoretical framework of
      particle acceleration in very young supernova remnants. These detections reveal
      the most energetic tip of a gamma-ray source population in an external galaxy and
      provide via 30 Dor C the unambiguous detection of gamma-ray emission from a
      superbubble. 

PMID- 25613890
TI  - Proteasomes. A molecular census of 26S proteasomes in intact neurons.
AB  - The 26S proteasome is a key player in eukaryotic protein quality control and in
      the regulation of numerous cellular processes. Here, we describe quantitative in
      situ structural studies of this highly dynamic molecular machine in intact
      hippocampal neurons. We used electron cryotomography with the Volta phase plate,
      which allowed high fidelity and nanometer precision localization of 26S
      proteasomes. We undertook a molecular census of single- and double-capped
      proteasomes and assessed the conformational states of individual complexes. Under
      the conditions of the experiment-that is, in the absence of proteotoxic stress
      only 20% of the 26S proteasomes were engaged in substrate processing. The
      remainder was in the substrate-accepting ground state. These findings suggest
      that in the absence of stress, the capacity of the proteasome system is not fully
      used.

PMID- 25613891
TI  - Teaming up against tsunamis.

PMID- 25613892
TI  - Cometary science. Time variability and heterogeneity in the coma of 67P/Churyumov
      Gerasimenko.
AB  - Comets contain the best-preserved material from the beginning of our planetary
      system. Their nuclei and comae composition reveal clues about physical and
      chemical conditions during the early solar system when comets formed. ROSINA
      (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) onboard the Rosetta
      spacecraft has measured the coma composition of comet 67P/Churyumov-Gerasimenko
      with well-sampled time resolution per rotation. Measurements were made over many
      comet rotation periods and a wide range of latitudes. These measurements show
      large fluctuations in composition in a heterogeneous coma that has diurnal and
      possibly seasonal variations in the major outgassing species: water, carbon
      monoxide, and carbon dioxide. These results indicate a complex coma-nucleus
      relationship where seasonal variations may be driven by temperature differences
      just below the comet surface. 

PMID- 25613894
TI  - Cometary science. Birth of a comet magnetosphere: a spring of water ions.
AB  - The Rosetta mission shall accompany comet 67P/Churyumov-Gerasimenko from a
      heliocentric distance of >3.6 astronomical units through perihelion passage at
      1.25 astronomical units, spanning low and maximum activity levels. Initially, the
      solar wind permeates the thin comet atmosphere formed from sublimation, until the
      size and plasma pressure of the ionized atmosphere define its boundaries: A
      magnetosphere is born. Using the Rosetta Plasma Consortium ion composition
      analyzer, we trace the evolution from the first detection of water ions to when
      the atmosphere begins repelling the solar wind (~3.3 astronomical units), and we
      report the spatial structure of this early interaction. The near-comet water
      population comprises accelerated ions (<800 electron volts), produced upstream of
      Rosetta, and lower energy locally produced ions; we estimate the fluxes of both
      ion species and energetic neutral atoms. 

PMID- 25613893
TI  - Cometary science. The morphological diversity of comet 67P/Churyumov-Gerasimenko.
AB  - Images of comet 67P/Churyumov-Gerasimenko acquired by the OSIRIS (Optical,
      Spectroscopic and Infrared Remote Imaging System) imaging system onboard the
      European Space Agency's Rosetta spacecraft at scales of better than 0.8 meter per
      pixel show a wide variety of different structures and textures. The data show the
      importance of airfall, surface dust transport, mass wasting, and insolation
      weathering for cometary surface evolution, and they offer some support for
      subsurface fluidization models and mass loss through the ejection of large chunks
      of material. 

PMID- 25613896
TI  - Cometary science. Subsurface properties and early activity of comet 67P/Churyumov
      Gerasimenko.
AB  - Heat transport and ice sublimation in comets are interrelated processes
      reflecting properties acquired at the time of formation and during subsequent
      evolution. The Microwave Instrument on the Rosetta Orbiter (MIRO) acquired maps
      of the subsurface temperature of comet 67P/Churyumov-Gerasimenko, at 1.6 mm and
      0.5 mm wavelengths, and spectra of water vapor. The total H2O production rate
      varied from 0.3 kg s(-1) in early June 2014 to 1.2 kg s(-1) in late August and
      showed periodic variations related to nucleus rotation and shape. Water
      outgassing was localized to the "neck" region of the comet. Subsurface
      temperatures showed seasonal and diurnal variations, which indicated that the
      submillimeter radiation originated at depths comparable to the diurnal thermal
      skin depth. A low thermal inertia (~10 to 50 J K(-1) m(-2) s(-0.5)), consistent
      with a thermally insulating powdered surface, is inferred. 

PMID- 25613895
TI  - Cometary science. The organic-rich surface of comet 67P/Churyumov-Gerasimenko as
      seen by VIRTIS/Rosetta.
AB  - The VIRTIS (Visible, Infrared and Thermal Imaging Spectrometer) instrument on
      board the Rosetta spacecraft has provided evidence of carbon-bearing compounds on
      the nucleus of the comet 67P/Churyumov-Gerasimenko. The very low reflectance of
      the nucleus (normal albedo of 0.060 +/- 0.003 at 0.55 micrometers), the spectral
      slopes in visible and infrared ranges (5 to 25 and 1.5 to 5% kA(-1)), and the
      broad absorption feature in the 2.9-to-3.6-micrometer range present across the
      entire illuminated surface are compatible with opaque minerals associated with
      nonvolatile organic macromolecular materials: a complex mixture of various types
      of carbon-hydrogen and/or oxygen-hydrogen chemical groups, with little
      contribution of nitrogen-hydrogen groups. In active areas, the changes in
      spectral slope and absorption feature width may suggest small amounts of water
      ice. However, no ice-rich patches are observed, indicating a generally dehydrated
      nature for the surface currently illuminated by the Sun. 

PMID- 25613897
TI  - Cometary science. On the nucleus structure and activity of comet 67P/Churyumov
      Gerasimenko.
AB  - Images from the OSIRIS scientific imaging system onboard Rosetta show that the
      nucleus of 67P/Churyumov-Gerasimenko consists of two lobes connected by a short
      neck. The nucleus has a bulk density less than half that of water. Activity at a
      distance from the Sun of >3 astronomical units is predominantly from the neck,
      where jets have been seen consistently. The nucleus rotates about the principal
      axis of momentum. The surface morphology suggests that the removal of larger
      volumes of material, possibly via explosive release of subsurface pressure or via
      creation of overhangs by sublimation, may be a major mass loss process. The shape
      raises the question of whether the two lobes represent a contact binary formed
      4.5 billion years ago, or a single body where a gap has evolved via mass loss. 

PMID- 25613898
TI  - Cometary science. Dust measurements in the coma of comet 67P/Churyumov
      Gerasimenko inbound to the Sun.
AB  - Critical measurements for understanding accretion and the dust/gas ratio in the
      solar nebula, where planets were forming 4.5 billion years ago, are being
      obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on
      the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov
      Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS
      (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35
      outflowing grains of mass 10(-10) to 10(-7) kilograms, and 48 grains of mass 10(
      5) to 10(-2) kilograms, respectively. Combined with gas data from the MIRO
      (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter
      Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass
      ratio of 4 +/- 2 averaged over the sunlit nucleus surface. A cloud of larger
      grains also encircles the nucleus in bound orbits from the previous perihelion.
      The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3
      inferred at perihelion from models of dust comae and trails. 

PMID- 25613899
TI  - Sea level change. Inherited landscapes and sea level change.
AB  - Enabled by recently gained understanding of deep-seated and surficial Earth
      processes, a convergence of views between geophysics and sedimentary geology has
      been quietly taking place over the past several decades. Surface topography
      resulting from lithospheric memory, retained at various temporal and spatial
      scales, has become the connective link between these two methodologically diverse
      geoscience disciplines. Ideas leading to the hypothesis of plate tectonics
      originated largely with an oceanic focus, where dynamic and mostly horizontal
      movements of the crust could be envisioned. But when these notions were applied
      to the landscapes of the supposedly rigid plate interiors, there was less success
      in explaining the observed anomalies in terrestrial topography. Solid-Earth
      geophysics has now reached a developmental stage where vertical movements can be
      measured and modeled at meaningful scales and the deep-seated structures can be
      imaged with increasing resolution. Concurrently, there have been advances in
      quantifying mechanical properties of the lithosphere (the solid outer skin of
      Earth, usually defined to include both the crust and the solid but elastic upper
      mantle above the asthenosphere). The lithosphere acts as the intermediary that
      transfers the effects of mantle dynamics to the surface. These developments have
      allowed us to better understand the previously puzzling topographic features of
      plate interiors and continental margins. On the sedimentary geology side, new
      quantitative modeling techniques and holistic approaches to integrating source-to
      sink sedimentary systems have led to clearer understanding of basin evolution and
      sediment budgets that allow the reconstruction of missing sedimentary records and
      past geological landscapes. 

PMID- 25613901
TI  - Interoceptive awareness changes the posterior insula functional connectivity
      profile.
AB  - Interoceptive awareness describes the ability to consciously perceive inner
      bodily signals, such as one's own heartbeat. The right anterior insula is assumed
      to mediate this ability. The role of the posterior insula, particularly posterior
      to-anterior insula signal flows is less clear in this respect. We scanned 27
      healthy people with either high or low interoceptive awareness using 3T fMRI,
      while they either monitored their own heartbeats, or external tones,
      respectively. We used a combination of network centrality and bivariate
      connectivity analyses to characterize changes in cortical signal flows between
      the posterior insula and the anterior insula during interoceptive awareness or
      exteroceptive awareness, respectively. We show that heartbeat monitoring was
      accompanied by reduced network centrality of the right posterior insula, and
      decreased functional connectivity strengths between the right posterior insula
      and the right mid and anterior insula. In addition, decreased signal flows
      between the right posterior insula and the bilateral anterior cingulate cortices,
      and the bilateral orbitofrontal cortices were observed during interoceptive
      awareness. Functional connectivity changes were only shown by people with high
      interoceptive awareness, and occurred specifically within the low-frequency range
      (i.e., <0.1 Hz). Both groups did not differ in their functional connectivity
      profiles during rest. Our results show for the first time that interoceptive
      awareness changes intra-insula signal flows in the low-frequency range. We
      speculate that the selective inhibition of slow signal progression along the
      posterior-to-anterior insula pathway during interoceptive awareness allows the
      salient and noiseless detection of one's own heartbeat.

PMID- 25613900
TI  - Proteomics. Tissue-based map of the human proteome.
AB  - Resolving the molecular details of proteome variation in the different tissues
      and organs of the human body will greatly increase our knowledge of human biology
      and disease. Here, we present a map of the human tissue proteome based on an
      integrated omics approach that involves quantitative transcriptomics at the
      tissue and organ level, combined with tissue microarray-based
      immunohistochemistry, to achieve spatial localization of proteins down to the
      single-cell level. Our tissue-based analysis detected more than 90% of the
      putative protein-coding genes. We used this approach to explore the human
      secretome, the membrane proteome, the druggable proteome, the cancer proteome,
      and the metabolic functions in 32 different tissues and organs. All the data are
      integrated in an interactive Web-based database that allows exploration of
      individual proteins, as well as navigation of global expression patterns, in all
      major tissues and organs in the human body. 

PMID- 25613902
TI  - Globus pallidus internus deep brain stimulation as rescue therapy for refractory
      dyskinesias following effective subthalamic nucleus stimulation.
AB  - BACKGROUND: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or
      globus pallidus internus (GPi) can effectively treat the motor symptoms of
      Parkinson's disease, but dual implantation is rare. We report the first cases of
      additional GPi stimulation as rescue therapy for disabling dyskinesias following
      successful STN stimulation. METHODS: Two patients, initially treated with
      bilateral STN DBS, underwent subsequent bilateral GPi DBS after the development
      of refractory dyskinesias within 1 and 6 years of STN surgery. Patients were
      evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) before and
      after surgeries for STN and GPi DBS. RESULTS: GPi DBS effectively suppressed
      dyskinesias in these patients and improved their quality of life, as demonstrated
      by their videos and UPDRS scores. CONCLUSIONS: Additional bilateral GPi DBS may
      be considered in the rare instance of patients who develop refractory dyskinesias
      early or late after bilateral STN DBS.

PMID- 25613903
TI  - MicroRNA-149 suppresses colorectal cancer cell migration and invasion by directly
      targeting forkhead box transcription factor FOXM1.
AB  - BACKGROUND/AIMS: The aim of this study is to investigate the clinicopathological
      and prognostic values of miR-149 expression and its roles in colorectal cancer
      (CRC) progression. METHODS: qRT-PCR was performed to detect miR-149 expression in
      CRC cell lines or tissues. Also, the clinical significance of miR-149 expression
      was investigated. The study further explored whether miR-149 inhibits migration
      and invasion of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1).
      RESULTS: miR-149 was significantly downregulated in CRC tissues, and low miR-149
      expression was observed to be significantly correlated with lymph node or distant
      metastasis and advanced TNM stage of CRC patients. Patients with low miR-149
      expression showed poorer prognosis than those with high miR-149 expression, and
      multivariate analyses indicated that status of miR-149 expression might be an
      independent prognostic factor. Gain- and loss - of - function assays indicated
      that miR-149 significantly inhibited growth, migration and invasion of CRC cells
      by targeting FOXM1. Furthermore, FOXM1 was significantly uiregulated in CRC
      tissues and inversely correlated with miR-149 expression. CONCLUSIONS: mR-149 was
      an independent prognostic factor and could inhibit migration and invasion of CRC
      cells, at least partially by targeting FOXM1.

PMID- 25613904
TI  - Non-adherence to peri-exacerbation pulmonary rehabilitation: the people have
      spoken.

PMID- 25613906
TI  - Activation of Sonic hedgehog signaling in ventricular cardiomyocytes exerts
      cardioprotection against ischemia reperfusion injuries.
AB  - Sonic hedgehog (SHH) is a conserved protein involved in embryonic tissue
      patterning and development. SHH signaling has been reported as a cardio
      protective pathway via muscle repair-associated angiogenesis. The goal of this
      study was to investigate the role of SHH signaling pathway in the adult
      myocardium in physiological situation and after ischemia-reperfusion. We show in
      a rat model of ischemia-reperfusion that stimulation of SHH pathway, either by a
      recombinant peptide or shed membranes microparticles harboring SHH ligand, prior
      to reperfusion reduces both infarct size and subsequent arrhythmias by preventing
      ventricular repolarization abnormalities. We further demonstrate in healthy
      animals a reduction of QTc interval mediated by NO/cGMP pathway leading to the
      shortening of ventricular cardiomyocytes action potential duration due to the
      activation of an inward rectifying potassium current sharing pharmacological and
      electrophysiological properties with ATP-dependent potassium current. Besides its
      effect on both angiogenesis and endothelial dysfunction we demonstrate here a
      novel cardio-protective effect of SHH acting directly on the cardiomyocytes. This
      emphasizes the pleotropic effect of SHH pathway as a potential cardiac
      therapeutic target. 

PMID- 25613907
TI  - Remote ischemic preconditioning and incidence of postoperative atrial
      fibrillation.
AB  - OBJECTIVES: Although remote ischemic preconditioning (RIPC) has shown favorable
      effects on ischemia-reperfusion injury, much remains unknown of its mechanisms
      and clinical significance. We hypothesized that RIPC would reduce the incidence
      of postoperative atrial fibrillation (POAF) following coronary artery bypass
      graft (CABG) surgery. In addition, we investigated whether RIPC could induce
      alterations of circulating microRNA in blood plasma. DESIGN: This is a single
      center, double-blind, randomized controlled trial. 92 adult patients referred for
      first-time isolated CABG surgery were randomly assigned to either RIPC (n = 45)
      or control (n = 47). The RIPC-stimulus comprised three 5-min cycles of upper arm
      ischemia, induced by inflating a blood pressure cuff to 200 mmHg, with an
      intervening 5 min reperfusion. Heart rhythm was assessed by telemetry. MicroRNA
      expression was assessed in plasma by real-time polymerase chain reaction.
      RESULTS: Of the 92 patients included in the study, 27 patients developed POAF
      (29%). 17 of these patients belonged to the RIPC group (38%), and 10 to the
      control group (21%). There were no significant alterations of microRNA
      expression. CONCLUSIONS: We did not observe a reduced incidence of POAF by RIPC
      before CABG surgery. Larger multi-center studies may be necessary to further
      clarify this issue.

PMID- 25613908
TI  - Protective effects of polyunsatutared fatty acids supplementation against
      testicular damage induced by intermittent hypobaric hypoxia in rats.
AB  - BACKGROUND: Intermittent hypobaric hypoxia (IHH) induces changes in the redox
      status and structure in rat testis. These effects may be present in people at
      high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA)
      can be effective in counteracting these oxidative modifications due to their
      antioxidants properties. The aim of the work was to test whether PUFA
      supplementation attenuates oxidative damage in testis by reinforcing the
      antioxidant defense system. The animals were divided into four groups (7 rats per
      group): normobaric normoxia (~750 tor; pO2 156 mmHg; Nx); Nx + PUFA, supplemented
      with PUFA (DHA: EPA = 3:1; 0.3 g kg(-1) of body weight per day); hypoxic hypoxia
      (~428 tor; pO2 90 mmHg; Hx) and, Hx + PUFA. The hypoxic groups were exposed in 4
      cycles to 96 h of HH followed by 96 h of normobaric normoxia for 32 days. Total
      antioxidant capacity (FRAP) and lipid peroxidation (malondialdehyde, MDA) in
      plasma and reduced (GSH)/oxidized glutathione (GSSG) ratio, tissue lipid
      peroxidation (TBARS) and antioxidant enzymes activity were assessed at the end of
      the study in testis. Also, SIRTUIN 1 and HIF-1 protein expression in testis were
      determined. RESULTS: IHH increased lipid peroxidation in plasma and HIF-1 protein
      levels in testis. In addition, IHH reduced FRAP levels in plasma, antioxidant
      enzymes activities and SIRTUIN 1 protein levels in testis. PUFA supplementation
      attenuated these effects, inducing the increases in FRAP, in the antioxidant
      enzymes activity and HIF-1 levels. CONCLUSIONS: These results suggest that the
      IHH model induces a prooxidant status in plasma and testis. The molecular
      protective effect of PUFA may involve the induction of an antioxidant mechanism.

PMID- 25613909
TI  - Hyperthyroidism evokes myocardial ceramide accumulation.
AB  - BACKGROUND: Thyroid hormones (THs) are key regulators of cardiac physiology as
      well as modulators of different cellular signals including the
      sphingomyelin/ceramide pathway. The objective of this study was to examine the
      effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart.
      METHODS: Male Wistar rats were treated for 10 days with triiodothyronine (T3) at
      a dose of 50ug/100g of body weight. Animals were then anaesthetized and samples
      of the left ventricle were excised. RESULTS: We have demonstrated that prolonged,
      in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine
      (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of
      sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in
      sphingolipids content were accompanied by a lesser activity of neutral
      sphingomyelinase and without significant changes in ceramidases activity.
      Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK)
      with subsequently increased expression of mitochondrial proteins: cytochrome c
      oxidase IV (COX IV), beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), carnityne
      palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha (PGC1alpha). CONCLUSIONS: We conclude that
      prolonged T3 treatment increases sphingolipids metabolism which is reflected by
      higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism
      induced increase in heart sphingomyelin (SM) concentration might be one of the
      mechanisms underlying maintenance of CER at relatively low level by its
      conversion to SM together with decreased S1P content.

PMID- 25613910
TI  - Hybridization of an Abeta-specific antibody fragment with aminopyrazole-based
      beta-sheet ligands displays striking enhancement of target affinity.
AB  - Determining Abeta levels in body fluids remains a powerful tool in the
      diagnostics of Alzheimer's disease. This report delineates a new supramolecular
      strategy which increases the affinity of antibodies towards Abeta to make
      diagnostic procedures more sensitive. A monoclonal antibody IC16 was generated to
      an N-terminal epitope of Abeta and the variable regions of the heavy and light
      chains were cloned as a recombinant protein (scFv). A 6 * histidine tag was fused
      to the C-terminus of IC16-scFv allowing hybridization with a small organic beta
      sheet binder via Ni-NTA complexation. On the other hand, a multivalent
      nitrilotriacetic acid (NTA)-equipped trimeric aminopyrazole (AP) derivative was
      synthesized based on a cyclam platform; and experimental evidence was obtained
      for efficient Ni(2+)-mediated complex formation with the histidine-tagged
      antibody species. In a proof of principle experiment the hybrid molecule showed a
      strong increase in affinity towards Abeta. Thus, the specific binding power of
      recombinant antibody fragments to their beta-sheet rich targets can be
      conveniently enhanced by non-covalent hybridization with small organic beta-sheet
      binders. 

PMID- 25613911
TI  - Food system sustainability and vulnerability: food acquisition during the
      military occupation of Kuwait.
AB  - OBJECTIVE: To document food acquisition experiences during Iraqi military
      occupation in Kuwait. DESIGN: Retrospective cross-sectional study. SETTING: Urban
      areas in Kuwait during occupation. SUBJECTS: Those living in Kuwait during the
      period of occupation, and aged between 15 to 50 years at the time of occupation,
      recruited by snowball sampling. A total of 390 completed questionnaires (response
      rate 78%, 202 female and 188 male) were returned. RESULTS: During the occupation,
      food became increasingly difficult to acquire. Two food systems emerged: (i) an
      underground Kuwaiti network linked to foods recovered from local food
      cooperatives and (ii) a black market supplied by food imported through Iraq or
      stolen locally. Food shortages led to reductions in meal size and frequency. Some
      respondents (47.7%) reported not having sufficient income to purchase food and
      22.1% had to sell capital items to purchase food. There was a significant
      increase (P<0.01) in home production, with 23.1% of people growing vegetables and
      39.0% raising animals to supplement food needs. Reduction in food wastage also
      emerged as a significant self-reported behaviour change. Respondents reported
      deterioration in the quality and availability of fish, milk, and fruit in
      particular. Despite a decrease in opportunities for physical activity, most
      respondents reported that they lost weight during the occupation. CONCLUSIONS:
      Although the Kuwaiti population fell by about 90 % and domestic food production
      increased during the 7-month occupation, the local population continued to rely
      heavily on imported food to meet population needs. The high prevalence of self
      reported weight loss indicates the inadequacies of this food supply. High
      apparent food security in systems which significantly exceed the ecological
      carrying capacity of the local environment and rely on mass food importation
      remains vulnerable.

PMID- 25613913
TI  - The stepped wedge cluster randomized trial and its potential for child health
      services research: a narrative review.

PMID- 25613912
TI  - Asthma in US Mexican-Origin Children in Early Childhood: Differences in Risk and
      Protective Factors by Parental Nativity.
AB  - OBJECTIVE: Over 900,000 Mexican-origin children in the United States have asthma,
      but little is known about the extent to which development of this condition
      reflects early childhood exposure to social and environmental risks. The
      objectives of this research are to demonstrate the roles of risk and protective
      factors in the prevalence and severity of asthma in this population and provide
      comparisons with other racial/ethnic groups. METHODS: Nationally representative
      data from the Early Childhood Longitudinal Study, Birth Cohort (n = 6900), with
      county-level ozone data appended to this file were analyzed using descriptive and
      multivariate regression methods. RESULTS: The odds of asthma diagnosis by 60
      months are approximately 50% higher among Mexican-origin children than for non
      Hispanic whites (P < .05) in multivariate analyses. Compared to those with
      foreign-born parents, Mexican-origin children with native-born parents have a
      lower likelihood of being breast-fed and greater chances of having risks
      including a family history of asthma, having respiratory illnesses and allergies,
      living with a smoker, and attending center-based child care. Mexican-origin
      children live in counties with over 3 times more elevated ozone days annually
      than non-Hispanic whites. CONCLUSIONS: Mexican-origin children experience a
      constellation of risk and protective factors, but those with US-born parents have
      elevated asthma risks compared to those with foreign-born parents. Asthma
      incidence and severity will likely increase as this population becomes
      increasingly integrated into US society.

PMID- 25613914
TI  - Xyloglucan and its interactions with other components of the growing cell wall.
AB  - The discovery of xyloglucan and its ability to bind tightly to cellulose has
      dominated our thinking about primary cell wall structure and its connection to
      the mechanism of cell enlargement for 40 years. Gene discovery has advanced our
      understanding of the synthesis of xyloglucan in the past decade, and at the same
      time new and unexpected results indicate that xyloglucan's role in wall structure
      and wall extensibility is more subtle than commonly believed. Genetic deletion of
      xyloglucan synthesis does not greatly disable cell wall functions. Nuclear
      magnetic resonance studies indicate that pectins, rather than xyloglucans, make
      the majority of contacts with cellulose surfaces. Xyloglucan binding may be
      selective for specific (hydrophobic) surfaces on the cellulose microfibril, whose
      structure is more complex than is commonly portrayed in cell wall cartoons.
      Biomechanical assessments of endoglucanase actions challenge the concept of
      xyloglucan tethering. The mechanically important xyloglucan is restricted to a
      minor component that appears to be closely intertwined with cellulose at limited
      sites ('biomechanical hotspots') of direct microfibril contact; these may be the
      selective sites of cell wall loosening by expansins. These discoveries indicate
      that wall extensibility is less a matter of bulk viscoelasticity of the matrix
      polymers and more a matter of selective control of slippage and separation of
      microfibrils at specific and limited sites in the wall. 

PMID- 25613915
TI  - Qualitative Research on Fatigue Associated with Depression: Content Validity of
      the Fatigue Associated with Depression Questionnaire (FAsD-V2).
AB  - BACKGROUND: Fatigue is one of the most common symptoms of major depressive
      disorder (MDD). The Fatigue Associated with Depression Questionnaire (FAsD) was
      developed to assess fatigue and its impact in patients with MDD. The current
      article presents the qualitative research conducted to develop and examine the
      content validity of the FAsD and FASD-Version 2 (FAsD-V2). METHODS: Three phases
      of qualitative research were conducted with patients recruited from a
      geographically diverse range of clinics in the US. Phase I included concept
      elicitation focus groups, followed by cognitive interviews. Phase II employed
      similar techniques in a more targeted sample. Phase III included cognitive
      interviews to examine whether minor edits made after Phase II altered
      comprehensibility of the instrument. Concept elicitation focused on patients'
      perceptions of fatigue and its impact. Cognitive interviews focused on
      comprehension, clarity, relevance, and comprehensiveness of the instrument. Data
      were collected using semi-structured discussion guides. Thematic analyses were
      conducted and saturation was examined. RESULTS: A total of 98 patients with MDD
      were included. Patients' statements during concept elicitation in phases I and II
      supported item development and content. Cognitive interviews supported the
      relevance of the instrument in the target population, and patients consistently
      demonstrated a good understanding of the instructions, items, response options,
      and recall period. Minor changes to instructions for the FAsD-V2 did not affect
      interpretation of the instrument. CONCLUSIONS: This qualitative research supports
      the content validity of the FAsD and FAsD-V2. These results add to previous
      quantitative psychometric analysis suggesting the FAsD-V2 is a useful tool for
      assessing fatigue and its impact in patients with MDD.

PMID- 25613917
TI  - Psychological Functioning in Youth With Spina Bifida Living in Colombia, South
      America.
AB  - OBJECTIVE: No studies have examined psychological functioning among youth with
      spina bifida (SB) living in a developing country where access to mental health
      resources is often scarce. This study compared self-reported psychological
      functioning between youth with SB living in Colombia, South America, and a
      demographically matched comparison group of healthy Colombian children. METHODS:
      22 children with SB and 22 comparison children completed assessments of
      depression and anxiety. Most (68.81%) participants were male, and the sample had
      a mean age of 13.25 years (SD = 2.65 years). RESULTS: Results revealed that
      children with SB reported greater total symptoms of depression (p < .05), but
      fewer worry-related symptoms of anxiety (p < .05). In addition, mean total scores
      for both depression and anxiety were in the nonclinical range for youth with SB.
      CONCLUSIONS: These findings highlight the need for targeted mental health (i.e.,
      depression) services for poor children with SB living in Colombia.

PMID- 25613916
TI  - I came to a fork in the DNA and there was RecG.
AB  - RecG is a potent, atypical, monomeric DNA helicase. It simultaneously couples ATP
      hydrolysis to duplex unwinding and rewinding, and to the displacement of proteins
      bound to the DNA. A model is presented for the localization of the enzyme to the
      inner membrane via its binding to SSB. Upon fork stalling, SSB targets the enzyme
      to the fork where it can act. RecG displays a strong preference for processing
      the fork in the regression direction, that is, away from the site of damage that
      initially led to fork arrest. Regression is mediated by strong binding of the
      wedge domain to the fork arms as well as to parental duplex DNA by the helicase
      domains. Once RecG has regressed the fork, it will dissociate leaving the now
      relaxed, Holliday junction-like DNA, available for further processing by enzymes
      such as RuvAB. 

PMID- 25613918
TI  - DNA-cellulose: an economical, fully recyclable and highly effective chiral
      biomaterial for asymmetric catalysis.
AB  - The challenge in DNA-based asymmetric catalysis is to perform a reaction in the
      vicinity of the helix by incorporating a small-molecule catalyst anchored to the
      DNA in a covalent, dative, or non-covalent yet stable fashion in order to ensure
      high levels of enantio-discrimination. Here, we report the first generation of a
      DNA-based catalyst bound to a cellulose matrix. The chiral biomaterial is
      commercially available, trivial to use, fully recyclable and produces high levels
      of enantioselectivity in various Cu(II)-catalyzed asymmetric reactions including
      Friedel-Crafts alkylations and Michael additions. A single-pass, continuous-flow
      process is also reported affording fast conversions and high enantioselectivities
      at low catalyst loadings thus offering a new benchmark in the field of DNA-based
      asymmetric catalysis.

PMID- 25613919
TI  - [Tutankhamun: evidence-based paleopathology versus "curse of the pharaoh"].
AB  - AIMS: Several speculations exist regarding possible diseases of the juvenile
      Pharaoh Tutankhamun. In this review published paleopathological findings and
      artificial alterations as well as suggestions regarding underlying diseases were
      characterized. MATERIAL AND METHODS: A selective search of the literature was
      carried out in the PubMed data base in an arbitrary time interval from 1960 to
      2013 (search terms: Tutankhamun, Pharaoh, paleopathology and mummy) and
      additional supplementary literature. RESULTS: Many artificial changes were a
      result of embalming and the examinations which have been performed since
      exhumation in 1922. Evidenced pathologies are craniofacial dysmorphia, bilateral
      alterations of the feet, malarial disease and an acute traumatic fracture of the
      knee. The cause of the knee fracture could no longer be reconstructed. Other
      trauma (e.g. skull fractures) or familial transmission of an eighteenth dynasty
      syndrome could not be confirmed. CONCLUSION: In addition to many artificial post
      mortem alterations, chronic and acute diseases could be verified in Tutankhamun,
      although the underlying causes are partially unknown.

PMID- 25613920
TI  - [Morphological and genetic aspects of Spitz tumors].
AB  - BACKGROUND: Spitzoid melanocytic neoplasms (i.e. Spitz nevi, atypical Spitz
      tumors and spitzoid melanoma) are a clinical, histopathological and molecular
      genetic heterogeneous group of melanocytic skin tumors. OBJECTIVES: Correlation
      of the histological features of spitzoid neoplasms with molecular genetic
      aberrations. MATERIAL AND METHODS: A review and summary of the scientific
      literature. RESULTS: Several histopathological and molecular genetic distinct
      subtypes of spitzoid lesions have been defined. Epithelioid Spitz tumors commonly
      show a loss of the BAP1 gene and BRAF mutations and are associated with a
      hereditary tumor predisposition syndrome. Desmoplastic Spitz tumors frequently
      harbor HRAS mutations and gains of the chromosome arm 11p. Plexiform Spitz tumors
      often display ALK translocations. The morphology of Spitz tumors with ROS1,
      NTRK1, RET and BRAF fusion genes seems to be unspecific and is currently not well
      characterized. CONCLUSION: Morphological features offer valuable clues to the
      underlying genetic aberrations in spitzoid neoplasms. Genetic aberrations can be
      found in the entire biological spectrum of spitzoid neoplasms (i.e. Spitz nevi,
      atypical Spitz tumors and spitzoid melanoma) and are, therefore, probably not
      useful for distinguishing benign from malignant tumors; however, genetic
      aberrations represent important targets for therapeutic interventions and offer
      investigational treatment options for patients with metastatic disease. The
      appearance of multiple epithelioid melanocytic tumors with BAP1 loss indicates a
      hereditary tumor syndrome and warrants genetic counseling and preventive
      screening of affected individuals.

PMID- 25613921
TI  - [Massive perivillous fibrin deposition, chronic histiocytic intervillositis and
      villitis of unknown etiology: Lesions of the placenta at the fetomaternal
      interface with risk of recurrence].
AB  - BACKGROUND: Maternal floor infarction/massive perivillous fibrin deposition
      (MFI/MFD), chronic histiocytic intervillositis (CHIV) and villitis of unknown
      etiology (VUE) are lesions of the placenta which are characterized
      morphologically. The cause is thought to be pathological
      immunotolerance/rejection reaction at the fetomaternal interface. The risk of
      recurrence is elevated and the lesions can lead to severe pediatric diseases.
      AIM: This article provides an overview of the pathological and anatomical
      characteristics of each of these lesions, including diagnostic criteria,
      suspected etiology, clinical relevance and suggested therapy options. MATERIAL
      AND METHODS: A selective search of the literature was carried out and experiences
      from own diagnostic clientele are presented. RESULTS AND DISCUSSION: While
      MFI/MFD and CHIV occur more rarely, VUE is relatively common occurring in up to
      15 % of placentas at term. Both MFI/MFD and CHIV can occur in the first and
      second trimester, while VUE typically manifests in the third trimester. All
      lesions can lead to intrauterine growth retardation or abortion and have a
      tendency towards disease recurrence. Furthermore, VUE and MFI/MFD can be
      associated with an adverse neurodevelopmental outcome in the children. For all
      these entities potential therapy strategies have been reported, which are mainly
      based on anticoagulation and immunosuppression in subsequent pregnancies.

PMID- 25613922
TI  - Metabolic and molecular responses to leucine-enriched branched chain amino acid
      supplementation in the skeletal muscle of alcoholic cirrhosis.
AB  - Skeletal muscle loss (sarcopenia) is a major clinical complication in alcoholic
      cirrhosis with no effective therapy. Skeletal muscle autophagic proteolysis and
      myostatin expression (inhibitor of protein synthesis) are increased in cirrhosis
      and believed to contribute to anabolic resistance. A prospective study was
      performed to determine the mechanisms of sarcopenia in alcoholic cirrhosis and
      potential reversal by leucine. In six well-compensated, stable, alcoholic
      patients with cirrhosis and eight controls, serial vastus lateralis muscle
      biopsies were obtained before and 7 hours after a single oral branched chain
      amino acid mixture enriched with leucine (BCAA/LEU). Primed-constant infusion of
      l-[ring-(2) H5 ]-phenylalanine was used to quantify whole-body protein breakdown
      and muscle protein fractional synthesis rate using liquid chromatography/mass
      spectrometry. Muscle expression of myostatin, mammalian target of rapamycin
      (mTOR) targets, autophagy markers, protein ubiquitination, and the intracellular
      amino acid deficiency sensor general control of nutrition 2 were quantified by
      immunoblots and the leucine exchanger (SLC7A5) and glutamine transporter
      (SLC38A2), by real-time polymerase chain reaction. Following oral administration,
      plasma BCAA concentrations showed a similar increase in patients with cirrhosis
      and controls. Skeletal muscle fractional synthesis rate was 9.63 +/- 0.36%/hour
      in controls and 9.05 +/- 0.68%/hour in patients with cirrhosis (P = 0.54).
      Elevated whole-body protein breakdown in patients with cirrhosis was reduced with
      BCAA/LEU (P = 0.01). Fasting skeletal muscle molecular markers showed increased
      myostatin expression, impaired mTOR signaling, and increased autophagy in
      patients with cirrhosis compared to controls (P < 0.01). The BCAA/LEU supplement
      did not alter myostatin expression, but mTOR signaling, autophagy measures, and
      general control of nutrition 2 activation were consistently reversed in cirrhotic
      muscle (P < 0.01). Expression of SLC7A5 was higher in the basal state in patients
      with cirrhosis than controls (P < 0.05) but increased with BCAA/LEU only in
      controls (P < 0.001). CONCLUSIONS: Impaired mTOR1 signaling and increased
      autophagy in skeletal muscle of patients with alcoholic cirrhosis is acutely
      reversed by BCAA/LEU.

PMID- 25613923
TI  - Novel heterozygous dysfibrinogenemia, Sumida (AalphaC472S), showed markedly
      impaired lateral aggregation of protofibrils and mildly lower functional
      fibrinogen levels.
AB  - INTRODUCTION: We encountered a 6-year-old girl with systemic lupus erythematosus.
      Although no bleeding or thrombotic tendency was detected, routine coagulation
      screening tests revealed slightly lower plasma fibrinogen levels, as determined
      by functional and antigenic measurements (functional/antigenic ratio=0.857),
      suggesting hypodysfibrinogenemia. MATERIALS AND METHODS: DNA sequence and
      functional analyses were performed on purified plasma fibrinogen, and recombinant
      variant fibrinogen was synthesized in Chinese hamster ovary cells based on the
      results obtained. RESULTS: DNA sequencing revealed a heterozygous AalphaC472S
      substitution (mature protein residue number) in the alphaC-domain. AalphaC472S
      fibrinogen indicated the presence of additional disulfide-bonded molecules, and
      markedly impaired lateral aggregation of protofibrils in spite of slightly lower
      functional plasma fibrinogen levels. Scanning electron microscopic observations
      showed a thin fiber fibrin clot, and t-PA and plasminogen-mediated clot lysis was
      similar to that of a normal control. Recombinant variant fibrinogen-producing
      cells demonstrated that destruction of the Aalpha442C-472C disulfide bond did not
      prevent the synthesis or secretion of fibrinogen, whereas the variant Aalpha
      chain of the secreted protein was degraded faster than that of the normal
      control. CONCLUSION: Our results suggest that AalphaC472S fibrinogen may cause
      dysfibrinogenemia, but not hypofibrinogenemia. The destruction and steric
      hindrance of the alphaC-domain of variant fibrinogen led to the impaired lateral
      aggregation of protofibrils and t-PA and plasminogen-mediated fibrinolysis, as
      well as several previously reported variants located in the alphaC-domain, and
      demonstrated the presence of disulfide-bonded molecules.

PMID- 25613924
TI  - Improving accuracy of International Classification of Diseases codes for venous
      thromboembolism in administrative data.
AB  - BACKGROUND: Increasingly, clinicians and researchers are using administrative
      data for clinical and outcomes research. However, they continue to question the
      accuracy of using International Classification of Diseases 9th Revision (ICD-9)
      codes alone to capture diagnoses, especially venous thromboembolism (VTE), in
      administrative data. OBJECTIVES: We tested the hypothesis that incorporation of
      treatment data and/or common procedural terminology (CPT) codes could improve
      accuracy of administrative data in detecting VTE. Research Design Using the
      Veterans Affairs Central Cancer Registry, we compared three competing algorithms
      by performing three cross-sectional studies. Algorithm 1 identified patients by
      ICD-9 codes alone. Algorithm 2 required VTE treatment in addition to ICD-9 codes.
      Algorithm 3 required a VTE diagnostic CPT code in addition to treatment and ICD-9
      criteria. RESULTS: The accuracy of ICD-9 codes alone for detection of VTE was
      marginal, with a PPV of 72%. The PPV was improved to 91% after addition of
      treatment data (algorithm 2). As compared to algorithm 2, addition of CPT codes
      (algorithm 3) did not significantly increase the accuracy of detecting VTE (PPV
      92%), but decreased sensitivity from 72% to 67%. CONCLUSIONS: Accuracy of VTE
      detection significantly improved with addition of treatment data to ICD-9 codes.
      This approach should facilitate use of administrative data to assess the
      incidence, epidemiology, and outcomes of VTE.

PMID- 25613925
TI  - New oral anticoagulants in the treatment of heparin-induced thrombocytopenia.
AB  - BACKGROUND: Heparin induced thrombocytopenia (HIT) is a potentially catastrophic
      syndrome with a high incidence of vascular thrombosis. There are little data on
      the efficacy of new oral anticoagulants (NOAC) in this setting. This study
      reports on the outcome of patients with HIT, treated with NOAC. MATERIALS AND
      METHODS: We retrospectively identified 22 patients with HIT who were treated by
      our group with a combination of NOAC and a short course of argatroban. These
      patients were evaluated in a prospective fashion for development of outcomes at a
      mean follow up of 19+/-3 months. RESULTS: There were a total of 5 deep and 2
      superficial vein thromboses diagnosed at index hospitalization. No patient
      developed arterial thrombosis. All patients tolerated NOAC and their platelet
      count normalized before discharge. At 19 months of follow-up, 6 patients had died
      of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous
      thromboembolism in any patient. CONCLUSIONS: In patients with HIT, a short course
      of parenteral treatment with argatroban followed by administration of a NOAC is
      highly safe and effective in prevention of thrombosis and normalization of
      platelet count. Development of HIT however, portends a poor prognosis independent
      of vascular thrombosis.

PMID- 25613926
TI  - A mouse model to study thrombotic complications of thalassemia.
AB  - Patients with beta-thalassemia major and mainly intermedia have an increased risk
      for developing venous and arterial thrombosis which may be related to circulating
      pathological red blood cells (RBC) and continuous platelet activation. In the
      present study we used a modified thalassemic mice model in conjunction with a
      "real-time" carotid thrombus formation procedure to investigate thrombotic
      complications of thalassemia. Heterozygous Th3/+ mice, which lack one copy of
      their beta-major and beta-minor globin genes, exhibit anomalies in RBC size and
      shape, chronic anemia and splenomegaly which recapitulate the phenotype of human
      beta-thalassemia intermedia. Flow cytometry measurements showed higher reactive
      oxygen species generation, indicating oxidative stress, in platelets and RBC of
      the thalassemic mice compared with wild type mice concomitant with an increase in
      reduced glutathione content which may represent a compensatory response to
      oxidative stress, and exposed phosphatidylserine which indicates platelet
      activation. To elucidate the effect of thalassemia on the development of arterial
      thrombosis, we studied photochemical-induced real-time thrombus formation in the
      carotid artery of these mice. The results indicated a significantly shorter "time
      to occlusion" in the thalassemic mice compared to wild type mice, which was
      prolonged following in vivo aspirin treatment. We suggest that this mouse model
      may contribute to our understanding of platelet activation and the
      hypercoagulable state in thalassemia and lay foundations to screening of anti
      platelet drugs as well as anti-oxidants as possible therapeutics for prevention
      of thrombosis in thalassemia patients. 

PMID- 25613927
TI  - An international, multicenter, prospective study of a prothrombin complex
      concentrate, Prothromplex Total(r), in anticoagulant reversal.
AB  - INTRODUCTION: Prothrombin complex concentrates (PCCs) are a common treatment
      option for the reversal of oral anticoagulation with vitamin K antagonists
      (VKAs). This study assessed efficacy and safety of Prothromplex Total(r).
      MATERIALS AND METHODS: Patients (>=18 years) with acquired prothrombin complex
      coagulation factor deficiency (international normalized ratio [INR] >= 2 at
      screening) due to oral VKAs, requiring reversal of anticoagulation, were treated
      with 25, 35, or 50 IU/kg BW PCC. After infusion, efficacy was assessed for 72 +/-
      4 hours. Adverse events (AEs) were captured for 15 days. RESULTS: Sixty-one
      subjects, 48 requiring interventional procedures and 13 with acute bleeds,
      received a single infusion of PCC. Of 59 subjects analyzed, all achieved
      normalization of INR (<= 1.3) within 30 +/- 5 minutes of infusion, demonstrating
      effective anticoagulant reversal. IVRs of factors II, VII, IX, and X ranged from
      1.12-2.03 IU/dL:IU/kg. Median INRs remained between 1.00 and 1.18 for up to 6
      hours. Overall efficacy of treatment was rated "excellent" for 60 subjects. Three
      AEs were deemed possibly related to treatment: 1 serious AE (SAE) of acute
      myocardial infarction (rated severe), 1 SAE of deep vein thrombosis (rated mild),
      and 1 AE of pyrexia (rated mild). Thrombotic adverse events (2/61, 3.3%) reported
      here are comparable to rates observed in other PCC studies. CONCLUSIONS: While
      there is a risk of thromboembolic events following treatment with PCC products,
      the number of events reported here was low and could have occurred without PCC
      treatment. The individualized, INR-based dosing of PCC used here for VKA
      anticoagulant reversal produces rapid normalization of INR to <= 1.3 within 30
      minutes.

PMID- 25613928
TI  - The contribution of genetic and environmental factors to changes in total and
      gamma' fibrinogen over 5 years.
AB  - INTRODUCTION: Increased fibrinogen is associated with cardiovascular disease
      risk. It is, however, not known to what extend environmental and genetic factors
      and/or their interaction influence changes in total and gamma' fibrinogen over
      time. We aimed to determine how variation within the fibrinogen gene as well as
      environmental factors influence the change in total and gamma' fibrinogen over
      time, and also whether gene-environment interactions influence total and gamma'
      fibrinogen on a cross-sectional and prospective level in Africans. MATERIALS AND
      METHODS: This prospective study consisted of 2010 participants at baseline and
      1288 participants at follow-up (5 years). RESULTS: The gene-environment
      interactions that were associated with fibrinogen concentration on a cross
      sectional level were: FGA 2224 G>A (rs2070011) with age (p=0.005), FGB Arg448Lys
      (rs4220) with HIV status (p<0.0001) and FGB 1038 G>A (rs1800791) with HbA1c
      (p=0.01). The only factor that independently influenced the change in total
      fibrinogen levels over time, was baseline CRP (p<0.0001) and FGG 10034 C>T
      (rs2066865) was the only single nucleotide polymorphism that independently
      influenced the change in fibrinogen gamma' levels over time (p=0.02). Only the
      FGG 9340 T>C (rs1049636) with HbA1c interaction was found to predict change in
      total fibrinogen concentrations over time (p=0.005). CONCLUSIONS: Gene
      environment interactions influenced fibrinogen levels cross-sectionally and also
      mediated changes in levels over time.

PMID- 25613929
TI  - [Professional quality of life in workers of the Toledo primary care health area].
AB  - OBJECTIVE: To determine the professional quality of life in the workers of the
      Toledo Primary Care Health Area and to analyse its components. MATERIAL AND
      METHODS: Descriptive, cross-sectional study, performed on workers of the Toledo
      Primary Care Health Area with an online self-administered questionnaire. MAIN
      VARIABLES: age, sex, health centre, professional group, seniority, management
      experience, collaboration in working groups, employment situation, and the PQL-35
      professional quality of life questionnaire. RESULTS: A total of 430 completed
      questionnaires were received (45.3%), of which 68.4% were women. The mean age was
      47.7+/-8.6 years old. Mean seniority was 21.5+/-9.7 years. PQL-35 results were:
      perception of management support 4.8+/-1.5; perception of workload 6.2+/-1.3;
      intrinsic motivation 7.9+/-1.1; job disconnection capacity 6.3+/-2.6; and
      professional quality of life 5.2+/-2.1. Gender differences were found in
      perception of management support (4.5+/-1.5 in males vs 4.9+/-1.5 in females;
      P=.031) and professional quality of life (4.9+/-2.0 vs 5.3+/-2.1; p=.044).
      Depending on the professional group, differences were found in the perception of
      workload (6.4+/-1.1 in physicians, 6.3+/-1.3 in nurses, 5.9+/-1.6 in non-sanitary
      professionals, and 5.3+/-1.2 in support units professionals; P<.001). Depending
      on the employment situation, differences were found in the intrinsic motivation
      (7.8+/-1.1 in proprietors, 8.3+/-1.1 in temporary workers, and 8.2+/-1.1 in
      substitutes; P=.002). CONCLUSIONS: The professional quality of life in the
      workers of the Toledo Primary Care Health Area is similar to that of other
      Spanish Health Areas, even in a time of economic crisis. The intrinsic motivation
      of the professionals is very high, in contrast with their high perception of
      workload and their low perception of management support.

PMID- 25613930
TI  - [Conflict of interests in biomedical Spanish journals. Tipology of activities
      declared by authors].

PMID- 25613931
TI  - Effectiveness of cochlear implant in inner ear bone malformations with anterior
      labyrinth involvement.
AB  - OBJECTIVE: To study electrical stimulation, auditory functionality, and language
      development in patients with inner ear malformations involving the anterior
      labyrinth who underwent cochlear implantation. STUDY DESIGN: Retrospective case
      review. SETTING: Reference hospital for cochlear implantation. PATIENTS: Review
      of 14 cases of severe hearing loss with major (common cavity deformity and
      cochlear hypoplasia) or minor (e.g., incomplete partition and basal turn aplasia)
      malformations. INTERVENTIONS: After cochlear implantation, data were gathered on
      the threshold (THR) and maximum comfort level (MCL) of the electrical stimulation
      and the number of functioning electrodes. Auditory responses to speech (EARS
      protocol) subtests were used to evaluate auditory functionality and language
      acquisition at 6, 12, and 24 months post-implantation. Tests used were: LIP
      profile, MTP (3, 6 and 12 words), OLD (open set test) and CLD (close set test).
      Results were compared with findings in a control group of 28 cochlear
      implantation patients without these malformations and with congenital hearing
      loss. RESULTS: The mean THR was 11.02MUC in patients with malformations versus
      3.5MUC in those without, a significant difference. The THR also significantly
      differed between groups with major and minor malformations. Fewer functioning
      electrodes were used in patients with malformations. Auditory functionality
      scores were best in controls than in patients with malformations, who scored
      <=50%, finding the lowest scores in those with major malformations. CONCLUSION:
      Patients with inner ear malformations undergoing cochlear implantation require
      greater stimuli to obtain an auditory response and have worse auditory
      functionality outcomes; these differences are greater in those with major versus
      minor malformations Nevertheless, cochlear implantation appears to be beneficial
      for all patients with these malformations to a greater or lesser extent.

PMID- 25613932
TI  - The effect of age on pediatric tympanoplasty outcomes: a comparison of preschool
      and older children.
AB  - OBJECTIVES: Determine whether the outcome of tympanoplasty in preschool children
      is different from that of older children. STUDY DESIGN: Retrospective case
      series. METHODS: Retrospective review of children having undergone a primary
      tympanoplasty by 4 surgeons for a tympanic membrane perforation between 2002 and
      2013. RESULTS: Data from 50 children age 2-4, 130 children age 5-7 and 105
      children age 8-13 years old were reviewed. Median follow-up was 7.5 months. On
      crude analysis, the incidence of anatomical success was not significantly
      different between the different age groups (p=0.38), the success rate was
      respectively 69.4%, 68.5% and 79.1% with an overall rate of 72.5%. 5.9% of all
      children required later insertion of tympanostomy tubes, 10.2% in preschool
      children. The post-operative audiology results were similar for all groups with a
      mean improvement of 9dB in the air-bone gap. When limiting the analysis to the
      155 children having at least 6 months of follow-up, the rate of success was
      respectively 50.0%, 60.8% and 74.0% (p=0.10). After multivariate analysis
      controlling for the effect of surgeon, approach and etiology, the odds ratio of
      perforation was respectively 5.48, 2.27 and 1.00 for the different age groups.
      CONCLUSION: Children younger than 4 years of age have the worst outcome after
      tympanoplasty. It remains uncertain whether the benefits of hearing improvement
      and quality of life may outweigh that of a high rate of a residual, usually
      smaller, perforation. Prospective studies are needed to confirm these results and
      delineate the patient characteristics and technique most likely to lead to
      successful results.

PMID- 25613933
TI  - Laryngeal pathology at school age following very preterm birth.
AB  - INTRODUCTION: Intubation injury resulting in laryngeal pathology is recognised as
      a possible complication of preterm birth, yet few published studies have examined
      such pathology and its relation to voice outcomes. This study reports on the
      results of prospective laryngeal function examinations of a cohort of very
      preterm children, all of whom presented with significant dysphonia at school age.
      MATERIALS AND METHODS: The laryngeal pathology of 20 very preterm children, born
      between 23 and 29 weeks gestation, was examined under halogen and stroboscopic
      conditions. Laryngeal structure and function were assessed using a rigid
      laryngoscope or a flexible nasendoscope. The approach was selected based on the
      age and/or likely compliance of the child. RESULTS: Nineteen children were found
      to have structural laryngeal pathology. Fourteen children presented with a chink
      to the posterior glottis and all demonstrated at least a mild degree of
      supraglottic hyperfunction. Other common findings were arytenoid prolapse and
      vocal fold immobility. More isolated findings included posterior scar band, vocal
      fold atrophy, arytenoid oedema and growth on the vocal folds. One child who
      presented with structural laryngeal pathology was never intubated. DISCUSSION:
      Supraglottic hyperfunction was common to all participants, regardless of the
      nature and extent of underlying structural laryngeal pathology. Posterior glottic
      chink was the most common pattern of incomplete vocal fold closure. These data
      support the hypothesis that very preterm children adopt supraglottic tightening
      to compensate for underlying laryngeal pathology. The mechanism underlying
      laryngeal damage in the child who was not intubated is unclear. CONCLUSIONS:
      Voice quality of very preterm children is affected by both laryngeal structure
      and function. A trial of behavioural voice treatment is recommended to evaluate
      any therapeutic response in this population.

PMID- 25613934
TI  - Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of
      the BCL11B tumor suppressor in T-cells.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T
      cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1
      oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells
      and/or leukemogenesis by dysregulating the cellular functions in the host. Recent
      studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B
      tumor suppressor protein. In the present study, we explored whether Tax and/or
      HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral
      transduction of Tax in a human T-cell line repressed the expression of BCL11B at
      both the protein and mRNA levels, whereas the transduction of HBZ had little
      effect on the expression. Tax mutants with a decreased activity for the NF
      kappaB, CREB or PDZ protein pathways still showed a reduced expression of the
      BCL11B protein, thereby implicating a different function of Tax in BCL11B
      downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein
      expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL
      derived cell lines, showed reduced BCL11B mRNA and protein expression relative to
      an uninfected T-cell line, and the greatest reductions were in the cells
      expressing Tax. Collectively, these results indicate that Tax is responsible for
      suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated
      repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of
      HTLV-1-infected T-cells. 

PMID- 25613935
TI  - A late 17alpha-hydroxylase deficiency diagnosis that leads to the discovery of a
      new CYP17 gene mutation.
AB  - 17alpha-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia.
      It leads to a reduced production of cortisol and sex steroids and thus an
      increase in adrenocorticotrophic hormone and gonadotrophins levels. High
      adrenocorticotrophic hormone levels result in an accumulation of 17
      deoxysteroids, such as deoxycorticosterone and corticosterone.
      Deoxycorticosterone and corticosterone have an important mineralocorticoid
      activity. We report the case of a 66-year-old woman who presented with
      hypertension and symptomatic hypokalaemia. Primary hyperaldosteronism was
      suspected and a right adrenal mass was removed. After surgery, the patient was
      referred to the endocrinology department for persistant hypokalaemia. Actually,
      she presented some signs of hypogonadism (impuberism, primary amenorrhea,
      infertility). Cortisol and 17OH-progesterone serum levels were low.
      Deoxycorticosterone and corticosterone were markedly elevated. The hypothesis of
      17alpha-hydroxylase deficiency was considered and confirmed by genetic
      exploration. A non-sense mutation c.938G>A (p.Trp313X) in exon 5 of the CYP17
      gene was found that had never been reported so far to our knowledge. Moreover,
      the patient's karyotype found a mosaic Turner syndrome. This case is particularly
      interesting because of the delay of diagnosis. The 17alpha-hydroxylase deficiency
      diagnosis is to be considered when hypertension is associated with hypokalaemia
      and hypogonadism, even in adult patients. 

PMID- 25613936
TI  - Iodine deficiency: Physiological, clinical and epidemiological features, and pre
      analytical considerations.
AB  - Low dietary intake is associated with severe pathologies (especially goiter and
      cretinism) that affect life quality. Iodine deficiency disorders are a major
      public health problem worldwide. In fact, 246 million school-aged children have
      insufficient iodine intake (data from 2012). Extrapoling this value to general
      population leads to the estimation that 1.9 billion people have insufficient
      iodine intake. So, it is crucial to interpret correctly data from iodine status
      survey. The World Health Organization recommends urinary iodine as the main
      indicator for the assessment of iodine status in epidemiological surveys. To
      improve the result, some considerations can be taken into account by the
      biologist, epidemiologist or public health physician for the realization of
      epidemiological surveys. After a reminder about the physiological and
      physiopathological feature of iodine, a description of some useful parameters was
      made to improve the exploration of iodine status in epidemiological surveys. 

PMID- 25613937
TI  - Surface engineering of porous silicon microparticles for intravitreal sustained
      delivery of rapamycin.
AB  - PURPOSE: To understand the relationship between rapamycin loading/release and
      surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal
      delivery system. METHODS: Three types of surface chemical modifications were
      studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal
      carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12,
      containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene;
      and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by
      grafting of 8-hydrocarbon chains to the resulting porous silica surface via a
      silanization. RESULTS: The efficiency of rapamycin loading follows the order
      (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 +/- 18) > pSi-COOH (68
      +/- 8) > pSi-C12 (36 +/- 6). Powder X-ray diffraction data showed that loaded
      rapamycin was amorphous and dynamic drug-release study showed that the
      availability of the free drug was increased by 6-fold (compared with crystalline
      rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations
      in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous
      release of the active drug and carrier degradation, and drug-loading capacity.
      Released rapamycin was confirmed with the fingerprints of the mass spectrometry
      and biologically functional as the control of commercial crystalline rapamycin.
      Single intravitreal injections of 2.9 +/- 0.37 mg pSiO2-C8-RAP into rabbit eyes
      resulted in more than 8 weeks of residence in the vitreous while maintaining
      clear optical media and normal histology of the retina in comparison to the
      controls. CONCLUSIONS: Porous silicon-based rapamycin delivery system using the
      pSiO2-C8 formulation demonstrated good ocular compatibility and may provide
      sustained drug release for retina.

PMID- 25613938
TI  - Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in
      infants with retinopathy of prematurity.
AB  - PURPOSE: To measure serum levels of bevacizumab and to compare serum levels of
      free vascular endothelial growth factor (VEGF) and insulin-like growth factor-1
      (IGF-1) in infants who were treated with either intravitreal injection of
      bevacizumab (IVB) or laser for type 1 retinopathy of prematurity (ROP). METHODS:
      Twenty-four infants with type 1 ROP were randomized into three treatment groups:
      IVB at 0.625 mg per eye per dose, IVB at 0.25 mg per eye per dose, and laser.
      Blood samples were collected prior to treatment and on posttreatment days 2, 14,
      42, and 60. Weekly body weights were documented from birth until 60 days post
      treatment. Serum levels of bevacizumab, free VEGF, and IGF-1 were measured with
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum bevacizumab was
      detected 2 days after the injection, peaked at 14 days, and persisted for up to
      60 days with half-life of 21 days. Area under the curve (AUC) analysis showed
      that systemic exposure to bevacizumab was variable among the subjects and was
      dose dependent. Serum free VEGF levels decreased in all three subgroups 2 days
      post treatment, with more significant reductions found in both IVB-treated
      groups, P = 0.0001. Serum IGF-1 levels were lower in both IVB-treated groups.
      CONCLUSIONS: Clearance of bevacizumab from the bloodstream in premature infants
      takes at least 2 months. Although serum free VEGF levels decreased following
      either laser or bevacizumab treatment, the reductions were more significant in
      the IVB-treated groups. Potential long-term effects of systemic exposure to
      bevacizumab in infants need to be studied further.

PMID- 25613939
TI  - MicroRNA-204-5p-Mediated Regulation of SIRT1 Contributes to the Delay of
      Epithelial Cell Cycle Traversal in Diabetic Corneas.
AB  - PURPOSE: We investigated how the microRNA (miRNA) modifies the expression of
      silent mating type information regulation 2 homolog 1 (SIRT1) in diabetic
      corneas. METHODS: The bioinformatic assay was used to predict which miRNAs might
      regulate the expression of SIRT1. A lipid transfection protocol was used to
      upregulate or knockdown the miRNA expression in TKE2 cells. Adenovirus-expressing
      short interfering RNA was used to knockdown the expression of SIRT1 in TKE2 cells
      and Ins2(Akita/+) mice were used to evaluate how miRNA promotes diabetic corneal
      epithelial wound healing. Cell cycle status was determined by flow cytometry
      assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay was used to analyze the cell viability. RESULTS: Nine miRNAs were selected
      for quantitative PCR (qPCR) detection after bioinformatics analysis. The miR-204
      5p merited further investigation, because it was increased almost 5-fold in
      diabetic corneal epithelia compared to nondiabetic control corneal epithelia.
      Using luciferase activity assay, we identified SIRT1 was a direct target of miR
      204-5p. The results of flow cytometry and MTT assay demonstrated that
      downregulation of miR-204-5p increased TKE2 cell growth and restored cell cycle
      progression in high glucose (HG) conditions by the regulation of Cyclin D1 and
      p16. Furthermore, we showed downregulation of miR-204-5p promoted HG attenuation
      of corneal epithelial wound healing via upregulation of SIRT1 in Ins2(Akita/+)
      mice. CONCLUSIONS: Our data provide firm evidence of a role for miR-204-5p in the
      direct regulation of SIRT1 in diabetic corneas and identified the miR-204-5p
      mediated regulation of SIRT1 contributes to the delay of epithelial cell cycle
      traversal in diabetic keratopathy. : Chinese Abstract.

PMID- 25613940
TI  - Restoration of foveal thickness and architecture after macula-off retinal
      detachment repair.
AB  - PURPOSE: To investigate the foveal changes after repair of macula-off
      rhegmatogenous retinal detachment (RRD). METHODS: Prospective comparative case
      series. Twenty-four eyes of 24 patients with macula-off/fovea-on detachment (n =
      9) and fovea-off detachment (n = 15) were studied. Serial optical coherence
      tomography (OCT) images taken at the same location were recorded at months 1, 3,
      6, and 12 after operation. Fellow eyes were used as controls. RESULTS: No
      significant changes of the central foveal thickness (CFT) were recorded in the
      fovea-on group over the follow-up. From month 1 to month 12, CFT increased
      significantly in the fovea-off group (P < 0.00001). In this group, a significant
      increase of the Henle fiber and outer nuclear layer (HFL + ONL, P = 0.007),
      external limiting membrane (ELM)-ellipsoid zone (EZ; P = 0.03), and EZ-retinal
      pigment epithelium (RPE) thicknesses (P < 0.00001) was recorded. Significant
      restoration of the integrity of the ELM in the fovea-off group (P < 0.001) and of
      the EZ and cone interdigitation zone in the fovea-on group and the fovea-off
      group was observed (P = 0.02 and P < 0.001, and P = 0.002 and P < 0.001,
      respectively). Twelve months after operation the foveal bulge restored in 8 of 15
      eyes of the fovea-off group. Multiple regression analysis showed that in the
      fovea-off group BCVA correlated with EZ-RPE thickness at months 1 and 12, whereas
      the improvement of BCVA during the 12 months follow-up correlated with the
      increase of ELM-RPE thickness. CONCLUSIONS: Optical coherence tomography scans
      taken serially at the same location showed a progressive increase of HNL+ONL, ELM
      EZ, and EZ-RPE thicknesses and restoration of the integrity of outer retinal
      bands after repair of fovea-off RRD. The use of software able to rescan at
      exactly the same area is crucial to correctly follow and interpret the
      reconstitution of the retinal bands and to correlate them to BCVA recovery.

PMID- 25613941
TI  - The association of longitudinal trend of fasting plasma glucose with retinal
      microvasculature in people without established diabetes.
AB  - PURPOSE: Structural changes of retinal vasculature, such as altered retinal
      vascular calibers, are considered as early signs of systemic vascular damage. We
      examined the associations of 5-year mean level, longitudinal trend, and
      fluctuation in fasting plasma glucose (FPG) with retinal vascular caliber in
      people without established diabetes. METHODS: A prospective study was conducted
      in a cohort of Chinese people age >=40 years in Guangzhou, southern China. The
      FPG was measured at baseline in 2008 and annually until 2012. In 2012, retinal
      vascular caliber was assessed using standard fundus photographs and validated
      software. A total of 3645 baseline nondiabetic participants with baseline and
      follow-up data on FPG for 3 or more visits was included for statistical analysis.
      The associations of retinal vascular caliber with 5-year mean FPG level,
      longitudinal FPG trend (slope of linear regression-FPG), and fluctuation
      (standard deviation and root mean square error of FPG) were analyzed using
      multivariable linear regression analyses. RESULTS: Multivariate regression models
      adjusted for baseline FPG and other potential confounders showed that a 10%
      annual increase in FPG was associated independently with a 2.65-MUm narrowing in
      retinal arterioles (P = 0.008) and a 3.47-MUm widening in venules (P = 0. 0.004).
      Associations with mean FPG level and fluctuation were not statistically
      significant. CONCLUSIONS: Annual rising trend in FPG, but not its mean level or
      fluctuation, is associated with altered retinal vasculature in nondiabetic
      people.

PMID- 25613942
TI  - Corneal epithelial wound healing and bactericidal effect of conditioned medium
      from human uterine cervical stem cells.
AB  - PURPOSE: To evaluate the effect of conditioned medium from human uterine cervical
      stem cells (CM-hUCESCs) on corneal epithelial healing in a rat model of dry eye
      after alkaline corneal epithelial ulcer. We also tested the bactericidal effect
      of CM-hUCESCs. METHODS: Dry eye was induced in rats by extraocular lacrimal gland
      excision, and corneal ulcers were produced using NaOH. Corneal histologic
      evaluation was made with hematoxylin-eosin (H&E) staining. Real-time PCR was used
      to evaluate mRNA expression levels of proinflammatory cytokines. We also studied
      the bactericidal effect of CM-hUCESCs in vitro and on infected corneal contact
      lenses (CLs) using Escherichia coli and Staphylococcus epidermidis bacteria. In
      addition, in order to investigate proteins from CM-hUCESCs that could mediate
      these effects, we carried out a human cytokine antibody array. RESULTS: After
      injury, dry eyes treated with CM-hUCESCs significantly improved epithelial
      regeneration and showed reduced corneal macrophage inflammatory protein-1 alpha
      (MIP-1alpha) and TNF-alpha mRNA expression as compared to untreated eyes and eyes
      treated with culture medium or sodium hyaluronate ophthalmic drops. In addition,
      we found in CM-hUCESCs high levels of proteins, such as tissue inhibitors of
      metalloproteinases 1 and 2, fibroblast growth factor 6 and 7, urokinase receptor,
      and hepatocyte growth factor, that could mediate these effects. In vitro, CM
      hUCESCs showed a clear bactericidal effect on both E. coli and S. epidermidis and
      CLs infected with S. epidermidis. Analyses of CM-hUCESCs showed elevated levels
      of proteins that could be involved in the bactericidal effect, such as the
      chemokine (C-X-C motif) ligands 1, 6, 8, 10, and the chemokine (C-C motif)
      ligands 5 and 20. CONCLUSIONS: Treatment with CM-hUCESCs improved wound healing
      of alkali-injured corneas and showed a strong bactericidal effect on CLs.
      Patients using CLs and suffering from dry eye, allergies induced by commercial
      solutions, or small corneal injuries could benefit from this treatment.

PMID- 25613943
TI  - Activation of liver X receptor protects inner retinal damage induced by N-methyl
      D-aspartate.
AB  - PURPOSE: To investigate whether activation of liver X receptors (LXRs) protects N
      methyl-D-aspartic (NMDA)-induced retinal neurotoxicity in mice and to explore the
      underlying mechanism. METHODS: Inner retinal damage was induced by intravitreal
      injection of NMDA. A synthetic LXR ligand TO901317 (TO90, 50 mg/kg/d) or vehicle
      was intragastrically administrated from 3 days before to 1 day or 7 days after
      NMDA injection. The severity of retinal damage was evaluated with histological
      analysis and TUNEL staining, and retinal functions were evaluated by ERG. The
      expressions of caspase-3, bax, bcl-2, TNF-alpha, and BACE1, the rate-limiting
      enzyme in the formation of amyloid beta (Abeta), in the retina were examined by
      real-time PCR and ELISA. The levels of LXRs, NF-kappaB subunit p65, p-p38 mitogen
      activated protein kinase (MAPK), and an LXR target gene ABCA1 were detected with
      real-time PCR and Western blotting. The localization and protein expression of
      Abeta in the retina was assessed by immunohistochemistry and Western blotting.
      RESULTS: The NMDA enhanced the expression of LXRbeta but not LXRalpha and ABCA1
      in mouse retina. Nevertheless, administration of TO90 after NMDA injection not
      only enhanced the expression of LXRbeta but also upregulated the level of ABCA1,
      suggesting retinal LXRs were activated in a ligand-dependent manner. The LXRalpha
      expression was unchanged in the vehicle and the TO90-treated groups. Activation
      of LXRbeta with TO90 inhibited cell death in the ganglion cell layer (GCL) and
      inner nuclear layer (INL), preserved ERG b- and a-wave amplitudes, and the b/a
      ratio in the NMDA-treated mice. Meanwhile, TO90 suppressed the elevation of
      apoptosis factors caspase-3 and bax induced by NMDA and upregulated the level of
      an antiapoptotic factor bcl-2. The TO90 also inhibited the increase of p-p38 MAPK
      and proinflammatory cytokine TNF-alpha after NMDA injection. Furthermore,
      activation of LXR attenuated the activation of NF-kappaB, and reduced gene
      expression of BACE1 and accumulation of Abeta induced by NMDA. CONCLUSIONS:
      Activation of LXRbeta with a synthetic LXR ligand TO90 protects the inner retinal
      damage induced by NMDA in mice. We speculate the protective effect is associated
      with inhibition of the NF-kappaB signaling pathway and reduction of Abeta
      formation in retina. The LXR agonists may become a new class of neuroprotective
      agent for retinal diseases associated with glutamate-induced excitotoxicity.

PMID- 25613944
TI  - Location of achromatizing pupil position and first Purkinje reflection in a
      normal population.
AB  - PURPOSE: Quality of vision in patients who have undergone corneal refractive
      surgery depends upon the optimal centration of the procedures used. The center of
      the pupil is used as a reference point in some corneal ablation procedures. The
      achromatic axis would be a more sensible option from an optical point of view,
      but it is not as readily detectable. As an alternative, other refractive
      techniques, like the small aperture corneal inlay for presbyopia correction, use
      the corneal reflex (first Purkinje image). To assess the relative position of
      these two marks, we developed a new instrument to simultaneously measure both the
      first Purkinje image (PI) and the intersection of the achromatic axis with the
      pupil plane. METHODS: The apparatus records images of the pupil and the PI when
      illuminated with a circle of infrared light-emitting diodes. A second optical
      path allows determination of the achromatic axis by using a subjective method.
      Both the positions of the PI and the achromatic axis intersection are determined
      simultaneously. RESULTS: A series of data were obtained in 48 eyes. The mean
      location of the achromatic point relative to the PI was [x = -0.05 +/- 0.15 mm; y
      = 0.09 +/- 0.18 mm]. Considered individually, in 55% of eyes, the distance
      between locations is less than 0.2 mm, and in 95% of eyes, distances are less
      than 0.4 mm. CONCLUSIONS: On average, achromatic axis crossing of the pupil and
      PI locations coincides within measurement errors. Although there was some
      intersubject variability, differences in location were less than 0.6 mm in all
      measured eyes.

PMID- 25613945
TI  - Assessing age-related changes in the biomechanical properties of rabbit lens
      using a coaligned ultrasound and optical coherence elastography system.
AB  - PURPOSE: To evaluate the capability of a novel, coaligned focused ultrasound and
      phase-sensitive optical coherence elastography (US-OCE) system to assess age
      related changes in biomechanical properties of the crystalline lens in situ.
      METHODS: Low-amplitude elastic deformations in young and mature rabbit lenses
      were measured by an US-OCE system consisting of a spectral-domain optical
      coherence tomography (OCT) system coaligned with a focused ultrasound system used
      to produce a transient force on the lens surface. Uniaxial compressional tests
      were used to validate the OCE data. RESULTS: The OCE measurements showed that the
      maximum displacements of the young rabbit lenses were significantly larger than
      those of the mature lenses, indicating a gradual increase of the lens stiffness
      with age. Temporal analyses of the displacements also demonstrate a similar trend
      of elastic properties in these lenses. The stress-strain measurements using
      uniaxial mechanical tests confirmed the results obtained by the US-OCE system.
      CONCLUSIONS: The results demonstrate that the US-OCE system can be used for
      noninvasive analysis and quantification of lens biomechanical properties in situ
      and possibly in vivo.

PMID- 25613946
TI  - Complex I subunit gene therapy with NDUFA6 ameliorates neurodegeneration in EAE.
AB  - PURPOSE: To address the permanent disability induced by mitochondrial dysfunction
      in experimental autoimmune encephalomyelitis (EAE). METHODS: Mice sensitized for
      EAE were rescued by intravitreal injection of adeno-associated viral vector
      serotype 2 with the complex I subunit gene scAAV-NDUFA6Flag. Controls were
      injected with a mitochondrially targeted red fluorescent protein (scAAV-COX8
      cherry). Another group received scAAV-COX8-cherry, but was not sensitized for
      EAE. Serial pattern electroretinograms (PERGs) and optical coherent tomography
      (OCT) evaluated visual function and structure of the retina at 1, 3, and 6 months
      post injection (MPI). Treated mice were killed 6 MPI for histopathology.
      Immunodetection of cleaved caspase 3 gauged apoptosis. Complex I activity was
      assessed spectrophotometrically. Expression of NDUFA6Flag in the retina and optic
      nerve were evaluated between 1 week to 1 month post injection by RT-PCR,
      immunofluorescence and immunoblotting. RESULTS: Reverse transcription-PCR and
      immunoblotting confirmed NDUFA6Flag overexpression with immunoprecipitation and
      blue native PAGE showing integration into murine complex I. Overexpression of
      NDUFA6Flag in the visual system of EAE mice rescued retinal complex I activity
      completely, axonal loss by 73%, and retinal ganglion cell (RGC) loss by 88%, RGC
      apoptosis by 66%, and restored the 33% loss of complex I activity in EAE to
      normal levels; thereby, preventing loss of vision indicated by the 43% reduction
      in the PERG amplitudes of EAE mice. CONCLUSIONS: NDUFA6 gene therapy provided
      long-term suppression of neurodegeneration in the EAE animal model suggesting
      that it may also ameliorate the mitochondrial dysfunction associated with
      permanent disability in optic neuritis and MS patients.

PMID- 25613947
TI  - Small fiber peripheral neuropathy in Wilson disease: an in vivo documentation by
      corneal confocal microscopy.
AB  - PURPOSE: Wilson disease (WD) is a disorder of hepatic copper metabolism leading
      to copper accumulation in hepatocytes and in extrahepatic organs, as the brain
      and cornea. The aim of this study was to investigate central corneal changes and
      in particular to assess the parameters of corneal subbasal nerve plexus (SBNP) in
      patients affected by WD, using corneal confocal microscopy (CCM). METHODS: A
      total of 24 patients affected by WD and 24 healthy control subjects were included
      in this cross-sectional comparative study. One eye of each subject was examined
      to quantify different corneal parameters. Mean cell diameter and mean cell
      density of the epithelium; number of fibers (NF), nerve fiber length density
      (NFLD), number of branchings (NBr), number of beadings (NBe), and fiber
      tortuosity (FT) of the SBNP; mean cell density of keratocytes of the anterior,
      medium, and posterior stroma; and mean cell density, polimegatism, and
      pleomorphism of the endothelium, and central corneal sensitivity were analyzed.
      RESULTS: Wilson disease induced significant alterations in SBNP, and corneal
      epithelium. The NFLD (P < 0.0001), NF (P = 0.001), NBe (P = 0.025), and NBr (P <
      0.0001) were significantly lower, whereas FT (P < 0.0001) was significantly
      higher in WD subjects compared to controls. Moreover mean epithelial cell
      diameter (P < 0.0001) and mean epithelial cell density (P < 0.0001) were
      significantly higher and lower compared to controls, respectively. CONCLUSIONS:
      The CCM showed significant corneal changes in SBNP, with concomitant corneal
      epithelium changes in WD, demonstrating the presence of small fiber peripheral
      neuropathy in these patients. The CCM may contribute to diagnosis and monitoring
      of the peripheral nervous system involvement in WD.

PMID- 25613948
TI  - Ultrasound-based quantification of vitreous floaters correlates with contrast
      sensitivity and quality of life.
AB  - PURPOSE: Clinical evaluation of floaters lacks quantitative assessment of
      vitreous structure. This study used quantitative ultrasound (QUS) to measure
      vitreous opacities. Since floaters reduce contrast sensitivity (CS) and quality
      of life (Visual Function Questionnaire [VFQ]), it is hypothesized that QUS will
      correlate with CS and VFQ in patients with floaters. METHODS: Twenty-two eyes (22
      subjects; age = 57 +/- 19 years) with floaters were evaluated with Freiburg
      acuity contrast testing (FrACT; %Weber) and VFQ. Ultrasonography used a
      customized probe (15-MHz center frequency, 20-mm focal length, 7-mm aperture)
      with longitudinal and transverse scans taken in primary gaze and a horizontal
      longitudinal scan through premacular vitreous in temporal gaze. Each scan set had
      100 frames of log-compressed envelope data. Within each frame, two regions of
      interest (ROIs) were analyzed (whole-central and posterior vitreous) to yield
      three parameters (energy, E; mean amplitude, M; and percentage of vitreous filled
      by echodensities, P50) averaged over the entire 100-frame dataset. Statistical
      analyses evaluated E, M, and P50 correlations with CS and VFQ. RESULTS: Contrast
      sensitivity ranged from 1.19%W (normal) to 5.59%W. All QUS parameters in two scan
      positions within the whole-central ROI correlated with CS (R > 0.67, P < 0.001).
      P50 in the nasal longitudinal position had R = 0.867 (P < 0.001). Correlations
      with VFQ ranged from R = 0.52 (P < 0.013) to R = 0.65 (P < 0.001). CONCLUSIONS:
      Quantitative ultrasound provides quantitative measures of vitreous echodensity
      that correlate with CS and VFQ, providing objective assessment of vitreous
      structure underlying the functional disturbances induced by floaters, useful to
      quantify vitreous disease severity and the response to therapy.

PMID- 25613949
TI  - Implantation of a novel telemetric intraocular pressure sensor in patients with
      glaucoma (ARGOS study): 1-year results.
AB  - PURPOSE: We investigated the safety of a telemetric IOP sensor and the accuracy
      of its IOP measurements in six patients with open-angle glaucoma and cataract.
      METHODS: The study design was a prospective, single-center clinical trial. Here
      we present 1-year follow-up data. A ring-shaped telemetric IOP sensor was
      implanted in the ciliary sulcus after implantation of the intracapsular lens,
      during planned cataract surgery. The sensor is encapsulated in silicone rubber
      and consists of a miniature device with eight pressure-sensitive capacitors and a
      circular microcoil antenna. IOP measurements are performed with a reader unit
      held in front of the eye. IOP is calculated as the differences between the
      absolute pressure inside the eye (pressure sensor) and that outside the eye
      (reader unit). RESULTS: The sensor was successfully implanted in all patients.
      Four patients developed sterile anterior chamber inflammation that resolved
      completely within 9 days after surgery with anti-inflammatory treatment. All
      patients showed mild to moderate pupillary distortion and pigment dispersion
      after surgery. Telemetric IOP measurement was performed in all patients at all
      visits, and the patients successfully performed self-tonometry at home after
      receiving instructions. Telemetric IOP values showed similar profiles compared to
      those of Goldmann applanation tonometry (GAT). Three patients showed a relevant
      IOP step during follow-up, and in one patient, negative values were obtained
      throughout the study. CONCLUSIONS: Despite early postoperative anterior chamber
      inflammation, the IOP sensor was well tolerated by all patients. We describe the
      first prospective clinical study of a noncontact IOP sensor that potentially
      enables continuous IOP monitoring in patients with glaucoma. The sensor shape and
      size needs to be adapted to avoid pupillary distortion and to confirm that IOP
      measurements are accurately recorded in comparison to those of GAT. (
      www.germanctr.de; number DRKS00003335.).

PMID- 25613950
TI  - Retinal adaptation abnormalities in primary open-angle glaucoma.
AB  - PURPOSE: Dynamic color and brightness adaptation are crucial for visual
      functioning. The effects of glaucoma on retinal ganglion cells (RGCs) could
      compromise these functions. We have previously used slow dynamic changes of light
      at moderate intensities to measure the speed and magnitude of subtractive
      adaptation in RGCs. We used the same procedure to test if RGC abnormalities cause
      slower and weaker adaptation for patients with glaucoma when compared to age
      similar controls. We assessed adaptation deficits in specific classes of RGCs by
      testing along the three cardinal color axes that isolate konio, parvo, and magno
      RGCs. METHODS: For one eye each of 10 primary open-angle glaucoma patients and
      their age-similar controls, we measured the speed and magnitude of adapting to
      1/32 Hz color modulations along the three cardinal axes, at central fixation and
      8 degrees  superior, inferior, nasal, and temporal to fixation. RESULTS: In all
      15 comparisons (5 locations * 3 color axes), average adaptation was slower and
      weaker for glaucoma patients than for controls. Adaptation developed slower at
      central targets than at 8 degrees  eccentricities for controls, but not for
      patients. Adaptation speed and magnitude differed between affected and control
      eyes even at retinal locations showing no visual field loss with clinical
      perimetry. CONCLUSIONS: Neural adaptation is weaker in glaucoma patients for all
      three classes of RGCs. Since adaptation abnormalities are manifested even at
      retinal locations not exhibiting a visual field loss, this novel form of
      assessment may offer a functional insight into glaucoma and an early diagnosis
      tool.

PMID- 25613951
TI  - Do socioeconomic factors influence breast cancer screening practices among Arab
      women in Qatar?
AB  - OBJECTIVES: Breast cancer incidence rates are rising in Qatar. Although the
      Qatari government provides subsidised healthcare and screening programmes that
      reduce cost barriers for residents, breast cancer screening (BCS) practices among
      women remain low. This study explores the influence of socioeconomic status on
      BCS among Arab women in Qatar. SETTING: A multicentre, cross-sectional
      quantitative survey was conducted with 1063 Arab women (87.5% response rate) in
      Qatar from March 2011 to July 2011. Women who were 35 years or older and had
      lived in Qatar for at least 10 years were recruited from seven primary healthcare
      centres and women's health clinics in urban and semiurban regions of Qatar.
      Associations between socioeconomic factors and BCS practice were estimated using
      chi(2) tests and multivariate logistic regression analyses. RESULTS: Findings
      indicate that less than one-third of the participants practised BCS
      appropriately, whereas less than half of the participants were familiar with
      recent BCS guidelines. Married women and women with higher education and income
      levels were significantly more likely to be aware of and to practise BCS than
      women who had lower education and income levels. CONCLUSIONS: Findings indicate
      low levels of awareness and low participation rates in BCS among Arab women in
      Qatar. Socioeconomic factors influence these women's participation in BCS
      activities. The strongest predictors for BCS practice are higher education and
      higher income levels. RECOMMENDATIONS: Additional research is needed to explore
      the impact of economic factors on healthcare seeking behaviours in the Middle
      Eastern countries that have a high national gross domestic product where
      healthcare services are free or heavily subsidised by the government; promotion
      of BCS and intervention strategies in these countries should focus on raising
      awareness about breast cancer, the cost and benefit of early screening for this
      disease, particularly among low-income women.

PMID- 25613952
TI  - The contribution of primary prevention medication and dietary change in coronary
      mortality reduction in England between 2000 and 2007: a modelling study.
AB  - OBJECTIVE: To analyse the falls in coronary heart disease (CHD) mortality in
      England between 2000 and 2007 and quantify the relative contributions from
      preventive medications and population-wide changes in blood pressure (BP) and
      cholesterol levels, particularly by exploring socioeconomic inequalities. DESIGN:
      A modelling study. SETTING: Sources of data included controlled trials and meta
      analyses, national surveys and official statistics. PARTICIPANTS: English
      population aged 25+ in 2000-2007. MAIN OUTCOME MEASURES: Number of deaths
      prevented or postponed (DPPs) in 2007 by socioeconomic status. We used the
      IMPACTSEC model which applies the relative risk reduction quantified in previous
      randomised controlled trials and meta-analyses to partition the mortality
      reduction among specific treatments and risk factor changes. RESULTS: Between
      2000 and 2007, approximately 20 400 DPPs were attributable to reductions in BP
      and cholesterol in the English population. The substantial decline in BP was
      responsible for approximately 13 000 DPPs. Approximately 1800 DPPs came from
      medications and some 11 200 DPPs from population-wide changes. Reduction in
      population BP prevented almost twofold more deaths in the most deprived quintile
      compared with the most affluent. Reduction in cholesterol resulted in
      approximately 7400 DPPs; approximately 5300 DPPs were attributable to statin use
      and approximately 2100 DPPs to population-wide changes. Statins prevented almost
      50% more deaths in the most affluent quintile compared with the most deprived.
      Conversely, population-wide changes in cholesterol prevented threefold more
      deaths in the most deprived quintile compared with the most affluent.
      CONCLUSIONS: Population-wide secular changes in systolic blood pressure (SBP) and
      cholesterol levels helped to substantially reduce CHD mortality and the
      associated socioeconomic disparities. Mortality reductions were, in absolute
      terms, greatest in the most deprived quintiles, mainly reflecting their bigger
      initial burden of disease. Statins for high-risk individuals also made an
      important contribution but maintained socioeconomic inequalities. Our results
      strengthen the case for greater emphasis on preventive approaches, particularly
      population-based policies to reduce SBP and cholesterol.

PMID- 25613953
TI  - Prognostic role of microRNA-205 in multiple human malignant neoplasms: a meta
      analysis of 17 studies.
AB  - OBJECTIVE: MicroRNA-205 (miRNA-205) was revealed as an attractive prognostic
      tumour biomarker in recent studies. However, the results of different studies
      have been inconsistent. We conducted a meta-analysis to elucidate the precise
      predictive value of miRNA-205 in various human malignant neoplasms. DESIGN: Meta
      analysis. DATA SOURCES: Qualified studies were identified up to 5 June 2014 by
      performing online searches in PubMed, EMBASE and Web of Science, and additional
      quality evaluations. PARTICIPANTS: Seventeen eligible studies with 4827 patients
      were ultimately enrolled in this meta-analysis. OUTCOME MEASURES: The
      heterogeneity between studies was assessed using I(2) statistics. Pooled HRs with
      95% CIs for patient survival and disease recurrence were calculated to
      investigate the correlation between miRNA-205 expression and cancer prognosis.
      RESULTS: Our results indicate that elevated miRNA-205 was significantly
      associated with enhanced overall survival in the breast cancer subgroup (HR=0.78,
      95% CI 0.67 to 0.91) and superior disease-free survival/recurrence-free survival
      in the adenocarcinoma subgroup (HR=0.68, 95% CI 0.49 to 0.94). CONCLUSIONS: miRNA
      205 is a promising biomarker for predicting the recurrence and progression of
      patients with adenocarcinomas or breast cancer. Owing to its complex roles,
      further relevant studies are warranted.

PMID- 25613954
TI  - Virtually impossible: limiting Australian children and adolescents daily screen
      based media use.
AB  - BACKGROUND: Paediatric recommendations to limit children's and adolescents'
      screen based media use (SBMU) to less than two hours per day appear to have gone
      unheeded. Given the associated adverse physical and mental health outcomes of
      SBMU it is understandable that concern is growing worldwide. However, because the
      majority of studies measuring SBMU have focused on TV viewing, computer use,
      video game playing, or a combination of these the true extent of total SBMU
      (including non-sedentary hand held devices) and time spent on specific screen
      activities remains relatively unknown. This study assesses the amount of time
      Australian children and adolescents spend on all types of screens and specific
      screen activities. METHODS: We administered an online instrument specifically
      developed to gather data on all types of SBMU and SBMU activities to 2,620 (1373
      males and 1247 females) 8 to 16 year olds from 25 Australian government and non
      government primary and secondary schools. RESULTS: We found that 45% of 8 year
      olds to 80% of 16 year olds exceeded the recommended < 2 hours per day for SBMU.
      A series of hierarchical linear models demonstrated different relationships
      between the degree to which total SBMU and SBMU on specific activities (TV
      viewing, Gaming, Social Networking, and Web Use) exceeded the < 2 hours
      recommendation in relation to sex and age. CONCLUSIONS: Current paediatric
      recommendations pertaining to SBMU may no longer be tenable because screen based
      media are central in the everyday lives of children and adolescents. In any
      reappraisal of SBMU exposure times, researchers, educators and health
      professionals need to take cognizance of the extent to which SBMU differs across
      specific screen activity, sex, and age.

PMID- 25613957
TI  - Foreword by HRH The Princess Anne.

PMID- 25613955
TI  - Overlapping mouse subcongenic strains successfully separate two linked body fat
      QTL on distal MMU 2.
AB  - BACKGROUND: Mouse chromosome 2 is linked to growth and body fat phenotypes in
      many mouse crosses. With the goal to identify the underlying genes regulating
      growth and body fat on mouse chromosome 2, we developed five overlapping
      subcongenic strains that contained CAST/EiJ donor regions in a C57BL/6J (hg/hg)
      background (hg is a spontaneous deletion of 500 Kb on mouse chromosome 10). To
      fine map QTL on distal mouse chromosome 2 a total of 1,712 F2 mice from the five
      subcongenic strains, plus 278 F2 mice from the HG2D founder congenic strain were
      phenotyped and analyzed. Interval mapping (IM) and composite IM (CIM) were
      performed on body weight and body fat traits on a combination of SNP and
      microsatellite markers, which generated a high-density genotyping panel. RESULTS:
      Phenotypic analysis and interval mapping of total fat mass identified two QTL on
      distal mouse chromosome 2. One QTL between 150 and 161 Mb, Fatq2a, and the second
      between 173.3 and 175.6 Mb, Fatq2b. The two QTL reside in different congenic
      strains with significant total fat differences between homozygous cast/cast and
      b6/b6 littermates. Both of these QTL were previously identified only as a single
      QTL affecting body fat, Fatq2. Furthermore, through a novel approach referred
      here as replicated CIM, Fatq2b was mapped to the Gnas imprinted locus.
      CONCLUSIONS: The integration of subcongenic strains, high-density genotyping, and
      CIM succesfully partitioned two previously linked QTL 20 Mb apart, and the
      strongest QTL, Fatq2b, was fine mapped to a ~2.3 Mb region interval encompassing
      the Gnas imprinted locus.

PMID- 25613956
TI  - Challenges in representation learning: a report on three machine learning
      contests.
AB  - The ICML 2013 Workshop on Challenges in Representation Learning(1) focused on
      three challenges: the black box learning challenge, the facial expression
      recognition challenge, and the multimodal learning challenge. We describe the
      datasets created for these challenges and summarize the results of the
      competitions. We provide suggestions for organizers of future challenges and some
      comments on what kind of knowledge can be gained from machine learning
      competitions. 

PMID- 25613958
TI  - Millennium Development Goals progress report.

PMID- 25613959
TI  - An index for quantifying female education and child health in emerging economies.
AB  - OBJECTIVE: To construct an index to measure female education and child health in
      the least developed countries (LDCs) of Asia. METHODS AND RESULTS: The design of
      our index includes the variables of female education and child health defined in
      the goals of the Millennium Declaration. For this purpose, we used Pena's P2
      distance method for 2011, the last year for which data were available for the set
      of variables. CONCLUSION: We have proposed a territorial measure and
      classification of female education and child health in the LDCs of Asia. We
      believe that the most striking differences between countries relate to basic
      female education variables such as girls' primary completion rate, and female
      literacy.

PMID- 25613960
TI  - Advancing the newborn and stillbirth global agenda: priorities for the next
      decade.
AB  - Remarkable advances have been made over the past decade in defining the burden of
      newborn mortality and morbidity and stillbirths, and in identifying interventions
      to address the major risk factors and causes of deaths. However, progress in
      saving newborn lives and preventing stillbirths in countries lags behind that for
      maternal mortality and for children aged 1-59 months. To accelerate progress,
      greater focus is needed on improving coverage, quality and equity of care at
      birth-particularly obstetric care during labour and childbirth, and care for
      small and sick newborns, which gives a triple return on investment, reducing
      maternal and newborn lives as well as stillbirths. Securing national-level
      political priority for newborn health and survival and stillbirths, and
      implementation of the Every Newborn Action Plan are critical to accomplishing the
      unfinished global agenda for newborns and stillbirths beyond 2015. 

PMID- 25613961
TI  - Child malnutrition and the Millennium Development Goals: much haste but less
      speed?
AB  - The Millennium Development Goals (MDGs) provide a framework for measuring the
      progress of nations. Several of these goals relate to child malnutrition, which
      remains an important contributor to child morbidity and mortality, accounting for
      approximately 45% of child deaths globally. A high proportion of undernourished
      children still live in Africa and parts of Asia, and the uneven rate of reduction
      in the prevalence of various types of child malnutrition among different income
      groups worldwide is worrying. Attempts to reduce child malnutrition should
      therefore begin from the grassroots by improving primary healthcare services in
      developing countries with particular focus on basic requirements. Adequate
      nutrition should be provided from birth, through infancy, preschool and early
      childhood to adolescence. The overall strategy should be one of careful and
      meticulous planning involving all development sectors with an emphasis on a
      bottom-up approach within a stable and disciplined polity; the MDGs will be only
      be useful if they are seen not as narrow objectives with unidirectional
      interventions but as multifaceted and co-ordinated. The setting of deadlines,
      whether 2015 or 2035, should not be emphasised so as to avoid hasty decision
      making. The top priority should be the implementation of the essential social
      services of basic education, primary healthcare, nutrition, reproductive health
      care, water and sanitation in partnership with the developed economies. 

PMID- 25613962
TI  - Millennium Development Goals: background.

PMID- 25613963
TI  - Ending preventable child deaths from pneumonia and diarrhoea by 2025. Development
      of the integrated Global Action Plan for the Prevention and Control of Pneumonia
      and Diarrhoea.
AB  - Despite the existence of low-cost and effective interventions for childhood
      pneumonia and diarrhoea, these conditions remain two of the leading killers of
      young children. Based on feedback from health professionals in countries with
      high child mortality, in 2009, WHO and Unicef began conceptualising an integrated
      approach for pneumonia and diarrhoea control. As part of this initiative, WHO and
      Unicef, with support from other partners, conducted a series of five workshops to
      facilitate the inclusion of coordinated actions for pneumonia and diarrhoea into
      the national health plans of 36 countries with high child mortality. This paper
      presents the findings from workshop and post-workshop follow-up activities and
      discusses the contribution of these findings to the development of the integrated
      Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea,
      which outlines the necessary actions for elimination of preventable child deaths
      from pneumonia and diarrhoea by 2025. Though this goal is ambitious, it is
      attainable through concerted efforts. By applying the lessons learned thus far
      and continuing to build upon them, and by leveraging existing political will and
      momentum for child survival, national governments and their supporting partners
      can ensure that preventable child deaths from pneumonia and diarrhoea are
      eventually eliminated.

PMID- 25613964
TI  - Country level economic disparities in child injury mortality.
AB  - BACKGROUND: Injuries are a neglected cause of child mortality globally and the
      burden is unequally distributed in resource poor settings. The aim of this study
      is to explore the share and distribution of child injury mortality across country
      economic levels and the correlation between country economic level and injuries.
      METHODS: All-cause and injury mortality rates per 100,000 were extracted for 187
      countries for the 1-4 age group and under 5s from the Global Burden of Disease
      Study 2010. Countries were grouped into four economic levels. Gross domestic
      product (GDP) per capita was used to determine correlation with injury mortality.
      RESULTS: For all regions and country economic levels, the share of injuries in
      all-cause mortality was greater when considering the 1-4 age group than under 5s,
      ranging from 36.6% in Organization for Economic Cooperation and Development
      countries to 10.6% in Sub-Saharan Africa. Except for Sub-Saharan Africa, there is
      a graded association between country economic level and 1-4 injury mortality
      across regions, with all low-income countries having the highest rates. Except
      for the two regions with the highest overall injury mortality rates, there is a
      significant negative correlation between GDP and injury mortality in Latin
      America and the Caribbean, Eastern Europe/Central Asia, Asia East/South-East and
      Pacific and North Africa/ Middle East. CONCLUSIONS: Child injury mortality is
      unevenly distributed across regions and country economic level to the detriment
      of poorer countries. A significant negative correlation exists between GDP and
      injury in all regions, exception for the most resource poor where the burden of
      injuries is highest.

PMID- 25613965
TI  - World Health Organization perspectives on the contribution of the Global Alliance
      for Vaccines and Immunization on reducing child mortality.
AB  - Child mortality has decreased substantially globally-from 12.6 million in 1990 to
      6.3 million in 2013-due, in large part to of governments' and organisations'
      work, to prevent pneumonia, diarrhoea and malaria, the main causes of death in
      the postneonatal period. In 2012, the World Health Assembly adopted the Decade of
      Vaccines Global Vaccine Action Plan 2011-2020 as the current framework aimed at
      preventing millions of deaths through more equitable access to existing vaccines
      for people in all communities. The Global Alliance for Vaccines and Immunization
      (GAVI) plays a critical role in this effort by financing and facilitating
      delivery platforms for vaccines, with focused support for the achievements of
      improved vaccination coverage and acceleration of the uptake of WHO-recommended
      lifesaving new vaccines in 73 low-income countries. The GAVI Alliance has
      contributed substantially towards the progress of Millennium Development Goal 4
      and to improving women's lives. By 2013, the GAVI Alliance had immunised 440
      million additional children and averted six million future deaths from vaccine
      preventable diseases in the world's poorest countries. The GAVI Alliance is on
      track to reducing child mortality to 68 per 1000 live births by 2015 in supported
      countries. This paper discusses the GAVI Alliance achievements related to
      Millennium Development Goal 4 and its broader contribution to improving women's
      lives and health systems, as well as challenges and obstacles it has faced.
      Additionally, it looks at challenges for the future and how it will continue its
      work related to reducing child mortality and improving women's health. 

PMID- 25613966
TI  - Essential medicines for children.
AB  - Millions of children die every year before they reach the age of 5 years, of
      conditions largely treatable with existing medicines. The WHO Model List of
      Essential Medicines was launched in 1977 to make the most necessary drugs
      available to populations whose basic health needs could not be met by the
      existing supply system. During the first 30 years of the Model List of Essential
      Medicines, children's needs were not systematically considered. After adoption of
      the 'Better medicines for children' resolution by the World Health Assembly,
      things changed. The first WHO Model List of Essential Medicines for Children was
      drawn up by a Paediatric Expert Subcommittee and adopted in October 2007. The
      most recent, 4th Model List of Essential Medicines for Children was adopted in
      2013. Data from country surveys show that access to essential medicines for
      children is still generally poor; much more work is needed. 

PMID- 25613967
TI  - Millennium Development Goal 5 and adolescents: looking back, moving forward.
AB  - Since the Millennium Declaration in 2000, unprecedented progress has been made in
      the reduction of global maternal mortality. Millennium Development Goal 5 (MDG 5;
      improving maternal health) includes two primary targets, 5A and 5B. Target 5A
      aimed for a 75% reduction in the global maternal mortality ratio (MMR), and 5B
      aimed to achieve universal access to reproductive health. Globally, maternal
      mortality since 1990 has nearly halved and access to reproductive health services
      in developing countries has substantially improved. In setting goals and targets
      for the post-MDG era, the global maternal health community has recognised that
      ultimate goal of ending preventable maternal mortality is now within reach. The
      new target of a global MMR of <70 deaths per 100 000 live births by 2030 is
      ambitious, yet achievable and to reach this target a significantly increased
      effort to promote and ensure universal, equitable access to reproductive,
      maternal and newborn services for all women and adolescents will be required. In
      this article, as we reflect on patterns, trends and determinants of maternal
      mortality, morbidity and other key MDG5 indicators among adolescents, we aim to
      highlight the importance of promoting and protecting the sexual and reproductive
      health and rights of adolescents as part of renewed global efforts to end
      preventable maternal mortality. 

PMID- 25613968
TI  - HIV and the Millennium Development Goals.
AB  - Millennium Development Goal (MDG) 6 has two HIV/AIDS commitments: to have halted
      and begun to reverse the spread of HIV/AIDS by 2015 and to ensure access to
      treatment among all those in need by 2010. Given the almost universal lack of
      access to HIV testing, prevention and treatment for children in high prevalence
      countries in 2000, the achievements of the past 15 years have been extraordinary,
      fuelled by massive donor investment, strong political commitment and ambitious
      global targets; however, MDG 6 is some way from being attained. Prevention of
      mother-to-child transmission (PMTCT) services have expanded enormously, with new
      infections among children falling by 58% between 2002 and 2013. There has been a
      shift towards initiation of lifelong antiretroviral therapy (ART) for pregnant
      and breastfeeding women, although low HIV testing rates in pregnancy, suboptimal
      PMTCT coverage and poor retention in care remain barriers to achieving HIV
      elimination among children. Early infant diagnosis has expanded substantially
      but, in 2013, only 44% of all HIV-exposed infants were tested before 2 months of
      age. Diagnosis of HIV, therefore, frequently occurs late, leading to delays in
      ART initiation. By the end of 2013, approximately 760 000 children were receiving
      ART, leading to 40% decline in AIDS-related mortality. However, only 24% of HIV
      infected children were receiving ART, compared with 36% of adults, leading to a
      'treatment gap'. In this review, we summarise progress and remaining challenges
      in reaching MDG 6 and discuss future strategies to achieve the ambitious goals of
      paediatric HIV elimination and universal access to treatment. 

PMID- 25613969
TI  - Abolishing inequity, a necessity for poverty reduction and the realisation of
      child mortality targets.
AB  - The first Millennium Development Goal (MDG 1) due in 2015 concerns poverty
      reduction. It has been claimed to be fulfilled on a global level, but still more
      than 1 billion people are living in abject poverty. There is a strong link
      between the economy and child survival, and only a minority of countries will
      have reached the MDG target for child mortality reduction by 2015. This paper
      discusses the relationship between poverty and child survival. It argues that a
      focus on equity is necessary to further reduce child mortality, through poverty
      reduction in absolute terms and also through targeting interventions for
      increased child survival to disadvantaged populations. The political will to
      actually achieve real change for those in greatest need is crucial but not to be
      taken for granted, and the distribution rather than the generation of wealth
      needs to be made a priority in the post-MDG era. 

PMID- 25613970
TI  - Malaria and the Millennium Development Goals.
AB  - Malaria, as a key disease of poverty, was singled out for special attention in
      the Millennium Project of 2000. Recent data suggest that malaria incidence and
      mortality are now declining all over the world. While these figures are cause for
      celebration, they must be interpreted carefully and with caution, particularly in
      relation to Africa. There are daunting challenges ahead for those working to
      achieve malaria eradication, not least of which is the poor quality of the data
      on which the work is based. In the absence of an affordable and fully effective
      vaccine, international funding for malaria control needs to be escalated still
      further. The money is essential to pay for universal access to a set of simple
      and proven interventions which would save the lives of millions of children over
      the next 15 years. 

PMID- 25613972
TI  - Millennium Development Goals: regional perspectives--India.

PMID- 25613971
TI  - Millennium Development Goals progress: a perspective from sub-Saharan Africa.
AB  - Sub-Saharan Africa is a highly diverse geo-political region. Any brief discussion
      of the progress made over the last 15 years towards the Millennium Development
      Goals (MDGs) will therefore not do justice to the true complexity of context and
      events. Our focus will be MDG4-to reduce child mortality by 66% from 1990 levels.
      We will touch briefly on MDG1, to eradicate extreme poverty and hunger, MDG2, to
      achieve universal primary education, and MDG5, to improve maternal health, which
      are inextricably linked with child well-being. We will also draw on an eclectic
      mix of additional global indicators. Acknowledging the limitations of this
      approach, we first offer a summary of expected progress and then point to debates
      on future goals.

PMID- 25613973
TI  - Child health in China in the Millennium Development Goal era.

PMID- 25613974
TI  - Millennium Development Goals: progress in Oceania.

PMID- 25613975
TI  - Policies, politics and the right to child health in South America.

PMID- 25613976
TI  - Child health in Central America and the Caribbean.

PMID- 25613977
TI  - Millennium Development Goals in Europe.

PMID- 25613978
TI  - Millennium Development Goals: update from North America.

PMID- 25613979
TI  - The post-2015 agenda: staying the course in maternal and child survival.
AB  - In this article, we draw on available evidence from Countdown to 2015 and other
      sources to make the case for keeping women and children at the heart of the next
      development agenda that will replace the Millennium Development Goal (MDG)
      framework after 2015. We provide a status update on global progress in achieving
      MDGs 4 and 5, reduce child mortality and improve maternal health, respectively-
      showing that although considerable mortality reductions have been achieved, many
      more women's and children's lives can be saved every day through available, cost
      effective interventions. We describe key underlying determinants of poor maternal
      and child health outcomes and the need for well-coordinated, comprehensive
      approaches for addressing them such as introducing a combination of nutrition
      specific and sensitive interventions to reduce pervasive malnutrition, targeting
      interventions to the underserved to reduce inequities in access to care, and
      increasing women's social status through improved access to education and income
      earning opportunities. In the wake of population momentum and emergencies such as
      the recent ebola outbreak and other humanitarian crises, health systems must be
      strengthened to be able to respond to these pressures. In conclusion, we
      underscore that the unfinished business of women's and children's health must be
      prioritized in the days ahead, and that ending preventable maternal and child
      deaths is not only a moral obligation but is achievable and essential to
      sustainable development moving forward.

PMID- 25613980
TI  - Coupled-cluster studies of extensive green fluorescent protein models using the
      reduced virtual space approach.
AB  - Accurate predictions of photoexcitation properties are a major challenge for
      modern methods of theoretical chemistry. We show here how approximate coupled
      cluster singles and doubles (CC2) calculations in combination with the reduced
      virtual space (RVS) approach can be employed in studies of excited states of
      large biomolecular systems. The RVS-CC2 approach is used for accurately
      predicting optical properties of the p-hydroxybenzylidene-dihydroimidazolinone (p
      HBDI) chromophore embedded in green fluorescent protein (GFP) models using
      quantum mechanical calculations in combination with large basis sets. We study
      the lowest excited states for the isolated and protein-embedded chromophore in
      two different protonation states, and show how omitting high-lying virtual
      orbitals in the RVS calculation of excitation energies renders large-scale CC2
      studies computationally feasible. We also discuss how the error introduced by the
      RVS approach can be systematically estimated and controlled. The obtained CC2
      excitation energies of 3.13-3.27 and 2.69-2.77 eV for the two protonation states
      of different protein models are in excellent agreement with the maxima of the
      experimental absorption spectra of 3.12-3.14 and 2.61-2.64 eV, respectively.
      Thus, the calculated energy splitting between the excited states of the two
      protonation states is 0.44-0.52 eV, which agrees very well with the experimental
      value of 0.48-0.51 eV. The calculations at the RVS-CC2 level on the protein
      models show the importance of using large QM regions in studies of
      biochromophores embedded in proteins. 

PMID- 25613981
TI  - Primary care-led dementia diagnosis services in South Gloucestershire: Themes
      from people and families living with dementia and health care professionals.
AB  - BACKGROUND: Primary care-led dementia services are an increasingly common form of
      service delivery; however, little is known about how these services are
      understood by their main stakeholders: the patients, family members and health
      care professionals. A primary care-led dementia service was piloted in the South
      Gloucestershire area during 2012, in which general practitioners (GPs) led the
      process of assessment and establishing a diagnosis. Of the 26 surgeries in the
      area, 11 initially agreed to participate in the pilot, with 12 more joining the
      project by the end of December 2012. AIM: The aim of this study was to provide a
      qualitative analysis of the experiences of health care professionals, patients
      and their families, of the new process of assessment, diagnosis and treatment of
      dementia within a primary care service. METHODS: Four patients, three care-givers
      and eight health care professionals were interviewed by peer researchers - all of
      whom were current care-givers. Interviews were transcribed and analysed using
      thematic analysis following Braun and Clarke's model. Data were also gathered
      about the number of referrals and what happened to these referrals. RESULTS:
      Themes gathered into four main areas: 'the journey', 'what next?', 'the benefits
      and limits of primary care' and 'are GPs getting it right'? CONCLUSIONS: The
      analysis provided a perspective on the experiences of patients, family members
      and health care professionals involved in the relocation of part of the memory
      service, from secondary care (memory clinics) to primary care, being piloted in
      South Gloucestershire. This identified both practical issues to be improved upon
      as well as possible barriers.

PMID- 25613982
TI  - Differential pathway coupling of the activated insulin receptor drives signaling
      selectivity by XMetA, an allosteric partial agonist antibody.
AB  - The monoclonal antibody XMetA is an allosteric partial agonist of the insulin
      receptor (IR), which activates the metabolic Akt kinase signaling pathway while
      having little or no effect on the mitogenic extracellular signal-regulated kinase
      (ERK) signaling pathway. To investigate the nature of this selective signaling,
      we have conducted a detailed investigation of XMetA to evaluate specific
      phosphorylation and activation of IR, Akt, and ERK in Chinese hamster ovary cell
      lines expressing either the short or long isoform of the human IR. Insulin
      activated both pathways, but the phosphorylation of Akt was more sensitive to the
      hormone than the phosphorylation of ERK. Maximally effective concentrations of
      XMetA elicited phosphorylation patterns similar to 40-100 pM insulin, which were
      sufficient for robust Akt phosphorylation, but had little effect on ERK
      phosphorylation. These data indicate that the preferential signaling of XMetA is
      due to an innate difference in pathway sensitivity of Akt versus ERK responses to
      IR activation and partial agonism by XMetA, rather than a separate pathway-biased
      mechanism. The metabolic selectivity of partial IR agonists like XMetA, if
      recapitulated in vivo, may be a desirable feature of therapeutic agents designed
      to regulate blood glucose levels while minimizing undesirable outcomes of
      excessive IR mitogenic activation. 

PMID- 25613984
TI  - Does Action Observation Training With Immediate Physical Practice Improve
      Hemiparetic Upper-Limb Function in Chronic Stroke?
AB  - BACKGROUND: The mirror neuron network provides a neural mechanism to prime the
      motor system through action observation in stroke survivors. OBJECTIVE: To
      examine whether action observation training with immediate physical practice
      improves upper-limb function in chronic stroke. METHODS: In a within-subject
      design, 14 chronic stroke survivors were assessed at baseline, then participated
      in 2 weeks of relaxation-sham plus physical practice (control) and reassessed.
      Thereafter, they participated in 2 weeks of action observation training coupled
      with immediate physical practice (intervention), followed by a final assessment.
      Duration of each action observation video sequence (priming exposure) was 30 s
      followed immediately by practice of the observed motor skill. RESULTS: There were
      significant improvements in control and intervention phases on primary outcome
      measures--Upper Extremity Fugl-Meyer Motor Assessment (FMA) and Functional Test
      of the Hemiparetic Upper Extremity (FTHUE)--as well as secondary outcome measures
      of self-perceptions of arm use. Gains in the primary outcomes were greater during
      the intervention phase (action observation + physical practice; FMA, 10.64; FTHUE
      level, 0.79, and tasks, 1.57) than during the control phase (relaxation-sham plus
      physical practice; FMA, 6.64; FTHUE level, 0.43, and tasks, 1.00). Interviews
      with participants highlighted the added value of watching an actor perform the
      movement before physically attempting to perform the action. CONCLUSIONS: This
      study provides preliminary evidence of the additive value of action observation
      plus physical practice over relaxation-sham plus physical practice. There appears
      to be capacity for further recovery of upper-limb function in chronic stroke that
      persists at least in the short term.

PMID- 25613983
TI  - Development of a tool for defining and identifying the dying patient in hospital:
      Criteria for Screening and Triaging to Appropriate aLternative care (CriSTAL).
AB  - OBJECTIVE: To develop a screening tool to identify elderly patients at the end of
      life and quantify the risk of death in hospital or soon after discharge for to
      minimise prognostic uncertainty and avoid potentially harmful and futile
      treatments. DESIGN: Narrative literature review of definitions, tools and
      measurements that could be combined into a screening tool based on routinely
      available or obtainable data at the point of care to identify elderly patients
      who are unavoidably dying at the time of admission or at risk of dying during
      hospitalisation. MAIN MEASUREMENTS: Variables and thresholds proposed for the
      Criteria for Screening and Triaging to Appropriate aLternative care (CriSTAL
      screening tool) were adopted from existing scales and published research findings
      showing association with either in-hospital, 30-day or 3-month mortality.
      RESULTS: Eighteen predictor instruments and their variants were examined. The
      final items for the new CriSTAL screening tool included: age >=65; meeting >=2
      deterioration criteria; an index of frailty with >=2 criteria; early warning
      score >4; presence of >=1 selected comorbidities; nursing home placement;
      evidence of cognitive impairment; prior emergency hospitalisation or intensive
      care unit readmission in the past year; abnormal ECG; and proteinuria.
      CONCLUSIONS: An unambiguous checklist may assist clinicians in reducing
      uncertainty patients who are likely to die within the next 3 months and help
      initiate transparent conversations with families and patients about end-of-life
      care. Retrospective chart review and prospective validation will be undertaken to
      optimise the number of prognostic items for easy administration and enhanced
      generalisability. Development of an evidence-based tool for defining and
      identifying the dying patient in hospital: CriSTAL.

PMID- 25613985
TI  - Corticopontocerebellar Connectivity Disruption in Congenital Hemiplegia.
AB  - BACKGROUND: Crossed cerebellar diaschisis is the disruption of functional
      connectivity between cerebrum and cerebellum after hemispheric unilateral brain
      lesions. In adults and to a lesser extent in children, crossed cerebellar
      diaschisis has been largely investigated by functional connectivity and
      demonstrated to influence paretic hand function. OBJECTIVE: We aim to demonstrate
      a disruption in structural corticopontocerebellar (CPC) connectivity in children
      with congenital brain lesions and examine its correlation with paretic hand motor
      function. METHODS: Thirty-six children (Manual Ability Classification System: I,
      n = 21; II, n = 15) with unilateral brain lesions and 18 controls were analyzed
      in a case-control study, and diffusion magnetic resonance imaging data were
      acquired at 3T. High angular resolution diffusion imaging probabilistic
      tractography was employed for the region of interest-based reconstruction of CPC
      tracts. To identify statistical differences in structural cerebrocerebellar
      connectivity between case and control groups, an asymmetry index based on the
      number of streamlines of CPC tracts was used. In the case group, the correlation
      between asymmetry index and hand function measures was also determined. RESULTS:
      Projections through the middle cerebellar peduncle to the contralateral cerebral
      cortex showed greater asymmetry in children with congenital unilateral brain
      lesion compared to controls (P = .03), thus indicating a disruption of structural
      cerebrocerebellar connectivity. The degree of asymmetry index showed a
      correlation (P < .03; r = -0.31) with impaired hand abilities in bimanual tasks.
      CONCLUSIONS: Disruption of structural cerebrocerebellar connectivity is present
      in patients with congenital unilateral brain injury and might be related to
      impaired hand function in bimanual skills, with potential implication in
      tailoring early intervention strategies.

PMID- 25613987
TI  - External fixation of tibial fractures.
AB  - External fixation for definitive or initial management of tibial fractures has a
      long history, with pin-to-bar external fixation being the standard of care for
      definitive management of tibial fractures. However, the use of this method
      lessened because of the increased popularity of intramedullary nailing and
      drawbacks associated with external fixation. This method is still commonly in use
      in the military environment and can be used for temporary stabilization of tibial
      fractures, especially in the setting of periarticular injuries. These fixators
      also may be useful for salvage of open and/or infected fractures that are
      unsuitable for internal fixation. 

PMID- 25613986
TI  - Placebo-Controlled Trial of Familiar Auditory Sensory Training for Acute Severe
      Traumatic Brain Injury: A Preliminary Report.
AB  - BACKGROUND: Sensory stimulation is often provided to persons incurring severe
      traumatic brain injury (TBI), but therapeutic effects are unclear. OBJECTIVE:
      This preliminary study investigated neurobehavioral and neurophysiological
      effects related to sensory stimulation on global neurobehavioral functioning,
      arousal, and awareness. METHODS: A double-blind randomized placebo-controlled
      trial where 15 participants in states of disordered consciousness (DOC), an
      average of 70 days after TBI, were provided either the Familiar Auditory Sensory
      Training (FAST) or Placebo of silence. Global neurobehavioral functioning was
      measured with the Disorders of Consciousness Scale (DOCS). Arousal and awareness
      were measured with the Coma-Near-Coma (CNC) scale. Neurophysiological effect was
      measured using functional magnetic resonance imaging (fMRI). RESULTS: FAST (n =
      8) and Placebo (n = 7) groups each showed neurobehavioral improvement. Mean DOCS
      change (FAST = 13.5, SD = 8.2; Placebo = 18.9, SD = 15.6) was not different, but
      FAST patients had significantly (P = .049; 95% confidence interval [CI] = -1.51, 
      .005) more CNC gains (FAST = 1.01, SD = 0.60; Placebo = 0.25, SD = 0.70). Mixed
      effects models confirm CNC findings (P = .002). Treatment effect, based on CNC,
      is large (d = 1.88, 95% CI = 0.77, 3.00). Number needed to treat is 2. FAST
      patients had more fMRI activation in language regions and whole brain (P values
      <.05) resembling healthy controls' activation. CONCLUSIONS: For persons with DOC
      29 to 170 days after TBI, FAST resulted in CNC gains and increased neural
      responsivity to vocal stimuli in language regions. Clinicians should consider
      providing the FAST to support patient engagement in neurorehabilitation.

PMID- 25613989
TI  - Novel hemodynamic index for assessment of aortic regurgitation after
      transcatheter aortic valve replacement.
AB  - BACKGROUND: Paravalvular aortic regurgitation (AR) after transcatheter aortic
      valve replacement (TAVR) has been associated with increased mortality. Precise
      assessment of the degree of AR within the catheterization laboratory is crucial
      to take counter measures, but it remains challenging. The aim of this study was
      to determine whether any modification to AR index can improve its performance.
      METHODS: The study included 64 patients treated with the Sapien valve (Edwards
      Life Sciences, Inc., Irvine, CA). The severity of AR was evaluated using
      echocardiography, angiography, and invasive hemodynamic parameters. We evaluated
      the time-integrated aortic regurgitation (TIAR) index as follows: (LV - Ao
      diastolic pressure time integral)/(LV systolic pressure time integral) * 100. We
      analyzed the AR index and TIAR index with the receiver operating characteristic
      (ROC) curve. RESULTS: AR was observed in 58 patients (90.7%) and graded as mild
      in 33 (51.6%), moderate in 20 (31.3%), or moderate to severe in 5 (7.8%)
      patients. No severe AR was detected. The AR index and TIAR index decreased
      proportionately to the increased severity of AR (P = 0.002 and P < 0.001,
      respectively). TIAR index < 80 was associated with a sensitivity of 86% and a
      specificity of 83% for >=mild AR. The area under the curve was greater for the
      TIAR index compared to the AR index (0.93 vs. 0.74). CONCLUSION: The TIAR index
      provides a better hemodynamic measure for assessing severity of AR compared to
      the AR index.

PMID- 25613988
TI  - Socioeconomic variation in the incidence of childhood coeliac disease in the UK.
AB  - BACKGROUND: Serological studies indicate that evidence of coeliac disease (CD)
      exists in about 1% of all children, but we lack estimates of current diagnostic
      patterns among children and how they vary by socioeconomic group. METHODS: We
      identified all children aged 0-18 years between 1993 and 2012 who were registered
      with general practices across the UK that contribute to a large population-based
      general practice database. The incidence of CD was evaluated in each quintile of
      the Townsend index of deprivation and stratified by age, sex, country and
      calendar year. RESULTS: Among 2,063,421 children, we identified 1247 CD
      diagnoses, corresponding to an overall CD incidence of 11.9 per 100,000 person
      years, which was similar across the UK countries and higher in girls than in
      boys. We found a gradient of CD diagnosis across socioeconomic groups, with the
      rate of diagnosis being 80% higher in children from the least-deprived areas than
      in those from the most-deprived areas (incident rate ratio 1.80, 95% CI 1.45 to
      2.22). This pattern held for both boys and girls and across all ages. Across all
      four countries of the UK, we found similar associations between CD and
      socioeconomic status. While CD incidence up to age 2 remained stable over the
      study period, diagnoses at older ages have almost tripled over the past 20 years.
      CONCLUSIONS: Children living in less socioeconomically deprived areas in the UK
      are more likely to be diagnosed with CD. Increased implementation of diagnostic
      guidelines could result in better case identification in more-deprived areas.

PMID- 25613990
TI  - Provision of Amniotic Fluid During Parenteral Nutrition Increases Weight Gain
      With Limited Effects on Gut Structure, Function, Immunity, and Microbiology in
      Newborn Preterm Pigs.
AB  - BACKGROUND: Small enteral boluses with human milk may reduce the risk of
      subsequent feeding intolerance and necrotizing enterocolitis in preterm infants
      receiving parenteral nutrition (PN). We hypothesized that feeding amniotic fluid,
      the natural enteral diet of the mammalian fetus, will have similar effects and
      improve growth and gastrointestinal (GI) maturation in preterm neonates receiving
      PN, prior to the transition to milk feeding. MATERIALS AND METHODS: Twenty-seven
      pigs, delivered by cesarean section at ~90% of gestation, were provided with PN
      and also fed boluses with amniotic fluid (AF; n = 13, 24-72 mL/kg/d) or no oral
      supplements (nil per os [NPO]; n = 14) until day 5 when blood, tissue, and fecal
      samples were collected for analyses. RESULTS: Body weight gain was 2.7-fold
      higher in AF vs NPO pigs. AF pigs showed slower gastric emptying, reduced meal
      induced release of gastric inhibitory peptide and glucagon-like peptide 2,
      changed gut microbiota, and reduced intestinal permeability. There were no
      effects on GI weight, percentage mucosa, villus height, plasma citrulline, hexose
      absorptive capacity, and digestive enzymes. Intestinal interleukin (IL)-1beta
      levels and expression of IL1B and IL8 were increased in AF pigs, while blood
      biochemistry and amino acid levels were minimally affected. CONCLUSION: Enteral
      boluses of AF were well tolerated in the first 5 days of life in preterm pigs
      receiving PN. Enteral provision of AF before the initiation of milk feeding may
      stimulate body growth and improve hydration in preterm infants receiving PN.
      Furthermore, it may improve GI motility and integrity, although most markers of
      GI maturation remain unchanged.

PMID- 25613991
TI  - Successful Fetoscopic Surgery to Release a Complete Obstruction of the Urethral
      Meatus in a Case of Congenital Megalourethra.
AB  - We report the successful use of fetoscopy to treat a case of severe low urinary
      tract obstruction (LUTO) secondary to a congenital megalourethra. A second
      trimester male fetus presented at 21 weeks of gestation with massive dilatation
      of the penile urethra. In addition, bilateral hydronephrosis, an enlarged and
      hypertrophic bladder, with progressive oligohydramnios were found, suggesting
      poor prognosis. Extensive counselling was performed and, after the approval from
      the local ethics committee and informed consent, patients accepted fetal therapy
      by fetoscopy. The procedure consisted in fetoscopic identification of the tip of
      the penis and confirmation of the complete absence of the urethral meatus.
      Thereafter, under combined endoscopic and ultrasound guidance a perforation of
      the tip of the penis was performed with contact diode laser, until an opening
      into the urethra was achieved. After the operation, resolution of the cystic
      penile dilation, with reduction of the penile size, and normalization of the
      amniotic fluid volume were observed. The pregnancy continued uneventfully and a
      normal male infant was born at term at the local hospital. The baby was
      developing normally with normal renal function at 6 months of age. Our report
      demonstrates that fetoscopic decompression of a distal urethra obstruction can
      achieve neonatal survival in the rare event of congenital megalourethra.

PMID- 25613992
TI  - HIV-1 adaptation to HLA: a window into virus-host immune interactions.
AB  - HIV-1 develops specific mutations within its genome that allow it to escape
      detection by human leukocyte antigen (HLA) class I-restricted immune responses,
      notably those of CD8(+) cytotoxic T lymphocytes (CTL). HLA thus represents a
      major force driving the evolution and diversification of HIV-1 within individuals
      and at the population level. Importantly, the study of HIV-1 adaptation to HLA
      also represents an opportunity to identify what qualities constitute an effective
      immune response, how the virus in turn adapts to these pressures, and how we may
      harness this information to design HIV-1 vaccines that stimulate effective
      cellular immunity. 

PMID- 25613993
TI  - The bacterial flagellar motor and its structural diversity.
AB  - The bacterial flagellum is a reversible rotary motor powered by an
      electrochemical-potential difference of specific ions across the cytoplasmic
      membrane. The H(+)-driven motor of Salmonella spins at ~300 Hz, whereas the Na(+)
      driven motor of marine Vibrio spp. can rotate much faster, up to 1700 Hz. A
      highly conserved motor structure consists of the MS ring, C ring, rod, and export
      apparatus. The C ring and the export apparatus show dynamic properties for
      exerting their functional activities. Various additional structures surrounding
      the conserved motor structure are observed in different bacterial species. In
      this review we summarize our current understanding of the structure, function,
      and assembly of the flagellar motor in Salmonella and marine Vibrio.

PMID- 25613995
TI  - Regulation of blood pressure and renal function by NCC and ENaC: lessons from
      genetically engineered mice.
AB  - The activity of the thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) and of the
      amiloride-sensitive epithelial Na(+) channel (ENaC) is pivotal for blood pressure
      regulation. NCC is responsible for Na(+) reabsorption in the distal convoluted
      tubule (DCT) of the nephron, while ENaC reabsorbs the filtered Na(+) in the late
      DCT and in the cortical collecting ducts (CCD) providing the final renal
      adjustment to Na(+) balance. Here, we aim to highlight the recent advances made
      using transgenic mouse models towards the understanding of the regulation of NCC
      and ENaC function relevant to the control of sodium balance and blood pressure.
      We thus like to pave the way for common mechanisms regulating these two sodium
      transporting proteins and their potential implication in structural remodeling of
      the nephron segments and Na(+) and Cl(-) reabsorption. 

PMID- 25613994
TI  - Auditory midbrain implant: research and development towards a second clinical
      trial.
AB  - The cochlear implant is considered one of the most successful neural prostheses
      to date, which was made possible by visionaries who continued to develop the
      cochlear implant through multiple technological and clinical challenges. However,
      patients without a functional auditory nerve or implantable cochlea cannot
      benefit from a cochlear implant. The focus of the paper is to review the
      development and translation of a new type of central auditory prosthesis for this
      group of patients that is known as the auditory midbrain implant (AMI) and is
      designed for electrical stimulation within the inferior colliculus. The rationale
      and results for the first AMI clinical study using a multi-site single-shank
      array will be presented initially. Although the AMI has achieved encouraging
      results in terms of safety and improvements in lip-reading capabilities and
      environmental awareness, it has not yet provided sufficient speech perception.
      Animal and human data will then be presented to show that a two-shank AMI array
      can potentially improve hearing performance by targeting specific neurons of the
      inferior colliculus. A new two-shank array, stimulation strategy, and surgical
      approach are planned for the AMI that are expected to improve hearing performance
      in the patients who will be implanted in an upcoming clinical trial funded by the
      National Institutes of Health. Positive outcomes from this clinical trial will
      motivate new efforts and developments toward improving central auditory
      prostheses for those who cannot sufficiently benefit from cochlear implants. This
      article is part of a Special Issue entitled <Lasker Award>. 

PMID- 25613996
TI  - Neurological complications and outcomes in the Berlin Heart EXCOR(r) pediatric
      investigational device exemption trial.
AB  - BACKGROUND: The Berlin Heart EXCOR((r)) ventricular assist device has been
      approved for use in the United States as a bridge to heart transplantation in
      children. We sought to characterize neurological events in children supported
      with the Berlin Heart EXCOR((r)) device. METHODS AND RESULTS: The multicenter
      prospective cohort consisted of all 204 children implanted with the Berlin Heart
      EXCOR((r)) device at 47 centers in North America between May 2007 and December
      2010. There were 73 neurological events in 59 patients, with 29% of the cohort
      experiencing >=1 neurological event. Events included 52 strokes in 43 patients
      (21% of the cohort). The neurological event rate was 0.51 events per 100 patient
      days. Many of the neurological events occurred early in the course of support,
      with 30 events recorded during the first 14 days of support. The mortality rate
      in participants with at least 1 neurological event was 42% (25 of 59),
      significantly higher than the 18% mortality rate (26 of 145) for those who did
      not have a neurological event (P=0.0006). Risk-factor analysis did not identify
      significant preimplantation predictors of neurological injury. CONCLUSIONS: Of
      children treated with the Berlin Heart EXCOR((r)) device as a bridge to
      transplant, 29% experienced at least 1 neurological event. The majority of
      neurological events were ischemic strokes, and many of those occurred early in
      the course of support. Neurological injury was the leading cause of death after
      implantation of the Berlin Heart EXCOR((r)) device. Risk stratification for
      stroke or neurological injury is not possible based on baseline preimplantation
      characteristics. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique
      Identifier: NCT00583661.

PMID- 25613997
TI  - End-stage renal disease attributed to acute tubular necrosis in the United
      States, 2001-2010.
AB  - BACKGROUND/AIMS: Though end-stage renal disease (ESRD) is increasingly attributed
      to acute tubular necrosis (ATN), contemporary trends in the rates of incidence
      and recovery of renal function are poorly defined. Hence, we set out to describe
      the clinical epidemiology of ESRD due to ATN between 2001 and 2010. METHODS: We
      examined United States Renal Data System data (n = 1,070,490) for 2001 through
      2010 to calculate the incidence rates and rates of renal recovery and death for
      patients with ESRD due to ATN treated with renal replacement therapy (RRT, n =
      27,603). RESULTS: Standardized incidence ratios increased between 2001-2002 and
      2009-2010 in the overall population (ratio 2.14), having risen in all demographic
      subgroups examined. Recovery of renal function was more likely in patients with
      ATN than in matched controls (cumulative incidence 23% vs. 2% at 12 weeks, 34%
      vs. 4% at 1 year), as was death (cumulative incidence 38% vs. 27% at 1 year).
      Hazards ratios for renal recovery increased stepwise with year of RRT inception
      to 1.34 (95% confidence interval 1.24-1.45) for 2009-2010 (vs. 2001-2002). In
      contrast, hazards ratios for death declined stepwise to 0.83 (0.79-0.87) in 2009
      2010. CONCLUSION: While the incidence of ESRD attributed to ATN has increased,
      prospects of renal recovery and survival have also increased. Despite substantial
      mortality risk on RRT, renal recovery is not a rare occurrence.

PMID- 25613999
TI  - Metabolism: acetate nourishes stressed tumour cells.

PMID- 25614000
TI  - Oncogenes: nothing but a G thing.

PMID- 25613998
TI  - Cloning and characterization of a novel sigma-like glutathione S-transferase from
      the giant panda parasitic nematode, Baylisascaris schroederi.
AB  - BACKGROUND: Baylisascaris schroederi, an intestinal nematode of the giant panda,
      is the cause of the often fatal disease, baylisascariasis. Glutathione S
      transferases (GSTs) are versatile enzymes that can affect parasite survival and
      parasite-host interactions and, are therefore, potential targets for the
      development of diagnostic tests and vaccines. METHODS: In this study, we
      identified a full-length cDNA that encoded a novel, secretory sigma-like GST (Bsc
      GSTsigma) from a B. schroederi-omic dataset. Following cloning and sequencing,
      sequence and structural analyses and comparative modeling were performed using
      online-bioinformatics and proteomics tools. The recombinant Bsc-GSTsigma (rBsc
      GSTsigma) protein was prokaryotically expressed and then used to detect
      antigenicity and reactivity using immunoblotting assays. In addition, the native
      protein in female adult B. schroederi was located via immunofluorescence
      techniques, while the preliminary ELISA-based serodiagnostic potential of rBsc
      GSTsigma was assessed in native and infected mouse sera. RESULTS: Bsc-GSTsigma
      contained a 621-bp open reading frame that encoded a polypeptide of 206 amino
      acids with two typical sigma GST domain profiles, including a GST_N_Sigma_like at
      the N-terminus and a GST_C_Sigma_like at the C-terminus. The presence of an N
      terminal signal sequence indicated that Bsc-GSTsigma was a secretory protein.
      Sequence alignment and phylogenetic analyses showed that Bsc-GSTsigma was a
      nematode-specific member of the Sigma class GSTs and shared the closest genetic
      distance with its homologue in Ascaris suum. Further comparative structure
      analyses indicated that Bsc-GSTsigma possessed the essential structural motifs
      (e.g., betaalphabetaalphabetabetaalpha) and the consensus secondary or tertiary
      structure that is typical for other characterized GSTsigmas. Immunolocalization
      revealed strong distributions of native Bsc-GSTsigma in the body hypodermis,
      lateral chords, gut epithelium, gut microvilli, oviduct epithelium, and ovaries
      of adult female worms, similar to its homologue in A. suum. Building on good
      immunogenic properties, rBsc-GSTsigma-based ELISA exhibited a sensitivity of
      79.1% and a specificity of 82.0% to detect anti-B. schroederi IgG antibodies in
      the sera of experimentally infected mice. CONCLUSION: This study presents a
      comprehensive demonstration of sequence and structural-based analysis of a new,
      secretory sigma-like GST from a nematode, and its good serodiagnostic performance
      suggests that rBsc-GSTsigma has the potential to detect B. schroederi and,
      therefore, could be used to develop an ELISA-based serological test to diagnose
      baylisascariasis in giant pandas.

PMID- 25614005
TI  - Metabolism: the mitochondria thief.

PMID- 25614006
TI  - Cell migration: changing shape.

PMID- 25614007
TI  - Therapeutic resistance: paradox breaking.

PMID- 25614010
TI  - A glass half full: Implications of screening for hepatitis C virus in the era of
      highly effective antiviral therapy.

PMID- 25614011
TI  - Ultra high-resolution HSQC: application to the efficient and accurate measurement
      of heteronuclear coupling constants.
AB  - A rapid NMR data acquisition strategy in terms of enhanced resolution per time
      unit for the simple and efficient determination of multiple coupling constants is
      described. The use of (13)C spectral aliasing combined by broadband (1)H
      homodecoupling allows accurate measurements from ultra high resolved 2D HSQC
      cross-peaks. 

PMID- 25614009
TI  - Critical roles of non-histone protein lysine methylation in human tumorigenesis.
AB  - Several protein lysine methyltransferases and demethylases have been identified
      to have critical roles in histone modification. A large body of evidence has
      indicated that their dysregulation is involved in the development and progression
      of various diseases, including cancer, and these enzymes are now considered to be
      potential therapeutic targets. Although most studies have focused on histone
      methylation, many reports have revealed that these enzymes also regulate the
      methylation dynamics of non-histone proteins such as p53, RB1 and STAT3 (signal
      transducer and activator of transcription 3), which have important roles in human
      tumorigenesis. In this Review, we summarize the molecular functions of protein
      lysine methylation and its involvement in human cancer, with a particular focus
      on lysine methylation of non-histone proteins. 

PMID- 25614008
TI  - S100 proteins in cancer.
AB  - In humans, the S100 protein family is composed of 21 members that exhibit a high
      degree of structural similarity, but are not functionally interchangeable. This
      family of proteins modulates cellular responses by functioning both as
      intracellular Ca(2+) sensors and as extracellular factors. Dysregulated
      expression of multiple members of the S100 family is a common feature of human
      cancers, with each type of cancer showing a unique S100 protein profile or
      signature. Emerging in vivo evidence indicates that the biology of most S100
      proteins is complex and multifactorial, and that these proteins actively
      contribute to tumorigenic processes such as cell proliferation, metastasis,
      angiogenesis and immune evasion. Drug discovery efforts have identified leads for
      inhibiting several S100 family members, and two of the identified inhibitors have
      progressed to clinical trials in patients with cancer. This Review highlights new
      findings regarding the role of S100 family members in cancer diagnosis and
      treatment, the contribution of S100 signalling to tumour biology, and the
      discovery and development of S100 inhibitors for treating cancer. 

PMID- 25614012
TI  - Giving and taking: representational building blocks of active resource-transfer
      events in human infants.
AB  - Active resource transfer is a pervasive and distinctive feature of human
      sociality. We hypothesized that humans possess an action schema of giving
      specific for representing social interactions based on material exchange, and
      specified the set of necessary assumptions about giving events that this action
      schema should be equipped with. We tested this proposal by investigating how 12
      month-old infants interpret abstract resource-transfer events. Across eight
      looking-time studies using a violation-of-expectation paradigm we found that
      infants were able to distinguish between kinematically identical giving and
      taking actions. Despite the surface similarity between these two actions, only
      giving was represented as an object-mediated social interaction. While we found
      no evidence that infants expected the target of a giving or taking action to
      reciprocate, the present results suggest that infants interpret giving as an
      inherently social action, which they can possibly use to map social relations via
      observing resource-transfer episodes. 

PMID- 25614013
TI  - Thyroid function in Rett syndrome.
AB  - INTRODUCTION: Thyroid function in Rett syndrome (RTT) has rarely been studied
      with unanimous results. However, this aspect is of great concern regarding the
      effect thyroid hormones (TH) have on proper mammalian brain development.
      OBJECTIVE: To evaluate the prevalence of abnormalities of thyroid function in a
      cohort of children with RTT. PATIENTS AND METHODS: Forty-five consecutive
      Caucasian girls (mean age: 8.6 +/- 5.3 years, range: 2.0-26.1) meeting the
      clinical criteria for RTT were recruited. In all of the subjects, we evaluated
      the serum concentrations of free-T3 (FT3), free-T4 (FT4), thyroid-stimulating
      hormone (TSH), thyroperoxidase autoantibodies, thyroglobulin autoantibodies
      (TgA), and TSH receptor (TSHr) autoantibodies. The results were compared with a
      group of 146 age-matched healthy Caucasian children and adolescent girls (median
      age: 9.5 years, range: 1.8-14.6) from the same geographical area. RESULTS: Mean
      FT3 and TSH levels were not significantly different between the RTT patients and
      controls. Nevertheless, FT4 levels were significantly higher in RTT patients than
      in controls (p < 0.005). In particular, 17.7% showed FT4 levels higher than the
      upper reference limit (vs. 0.7% of controls, p < 0.0001), whereas 12 patients
      (26.7%) showed higher FT3 levels than the upper reference limit, significantly
      differing in respect to controls (2.0%, p < 0.0001). Finally, 5 patients (11.1%)
      showed higher levels of TSH, statistically differing from the control subjects
      (2.0%, p < 0.0001). However, evaluating the patients on the basis of different
      RTT genotype subgroups, patients with CDKL5 deletions showed significantly higher
      FT4 values than patients with MeCP2 deletions (p < 0.05). On the other hand,
      patients with other types of MeCP2 mutations also showed FT4 levels significantly
      higher than patients with MeCP2 deletions (p < 0.05). In fact, out of 8 patients
      with FT4 levels higher than the upper references limit, 3 of them presented with
      CDKL5 deletions (3 patients, 37.5%), 4 (50%) had MeCP2 mutations, and 1 (12.5%)
      belonged to the subgroup of MeCP2 deletions. However, when analyzing FT3 levels
      of the 12 patients showing higher FT3 levels than the upper references limit, 6
      (50%) belonged to the subgroup with MeCP2 mutations, 4 (33.3%) to the subgroup
      with MeCP2 deletions, and 2 (16.7%) to the subgroups with CDKL5 deletions.
      Furthermore, no patient with RTT was positive for antithyroglobulin
      autoantibodies, antithyroid peroxidase, or anti-TSHr, with no statistical
      differences in respect to the controls. L-thyroxine treatment was not necessary
      for any patient. CONCLUSIONS: Abnormalities of thyroid function are not rare in
      RTT. The possible relationship between these disorders and the RTT phenotype
      should be confirmed and studied. Children with RTT should be screened for
      potential thyroid dysfunction.

PMID- 25614015
TI  - Device connectivity: the next big wave in diabetes.
AB  - Patients with diabetes have to take numerous factors/data into their therapeutic
      decisions in daily life. Connecting the devices they are using by feeding the
      data generated into a database/app is supposed to help patients to optimize their
      glycemic control. As this is not established in practice, the different
      roadblocks have to be discussed to open the road. That large telecommunication
      companies are now entering this market might be a big help in pushing this
      forward. Smartphones offer an ideal platform for connectivity solutions. 

PMID- 25614016
TI  - Assessing rumination response style among undergraduate nursing students: A
      construct validation study.
AB  - BACKGROUND: Rumination is one of the risk factors for mental health problems
      among nursing students. Rumination refers to repetitive thoughts focusing on
      negative emotions. There is a need to use an appropriate instrument to detect
      rumination to prevent the development of emotional problems. The ruminative
      response scale (RRS) is an instrument widely used to assess rumination levels in
      adult populations. It is inconclusive if the scale can be used for younger people
      like nursing students. OBJECTIVES: This study aimed to examine the psychometric
      properties of the 10-item ruminative response scale (RRS-10) in undergraduate
      nursing students. DESIGN: A cross-sectional research design was used. SETTINGS:
      This study was undertaken at one of the universities in Thailand. PARTICIPANTS: A
      sample of 747 undergraduate nursing students was recruited. METHOD: Data were
      collected through a self-administered questionnaire, containing the 10-item RRS
      and Thoughts, Feelings and Experiences Questionnaire, and personal information.
      Exploratory/confirmatory factor analyses and correlational analyses were
      performed to test the construct and concurrent validity of the RRS respectively.
      Cronbach's alphas were used as parameters for the internal consistency
      reliability. RESULTS: The RRS-10 had two distinct factors: brooding (moody
      pondering) and reflection (analysing depression-relating situations). Adequate
      model fit indices were obtained and significant factor loadings were observed,
      indicating acceptable construct validity. These two factors had significant
      correlations with emotional distress, depression, anxiety, and hopelessness,
      supporting concurrent validity of the scale. Cronbach's alphas were 0.71 and 0.73
      for the brooding and reflection factors respectively, suggesting good
      reliability. CONCLUSION AND RECOMMENDATION: The RRS-10 demonstrated satisfactory
      psychometric properties. Therefore, it can be used to assess rumination response
      style among undergraduate nursing students in Thailand. Future research can test
      the scale on nursing students or youths in other countries.

PMID- 25614014
TI  - Recent topics in chemical and clinical research on glycated albumin.
AB  - The measuring method for glycated albumin (GA) has been developed as a new
      glycemic control marker since the beginning of the 21st century. Since GA has an
      advantage in reflecting glycemic status over a shorter period than hemoglobin A1c
      (HbA1c), much research and many reviews have been reported. However, so far there
      have been few reports on glycation sites based on the tertiary structure of human
      serum albumin (HSA) and the comparison of glycation rates between GA and HbA1c in
      detail. The present review discusses how the glycation sites of lysine residues
      in HSA are modified with glucose, whereas the glycation sites of lysine residues
      are located inside of HSA as well as the direct comparison of glycation rates
      between GA and HbA1c using human blood. Moreover, the most recent clinical
      researches on GA are described. 

PMID- 25614017
TI  - An exploration of nursing preceptorship and functions and nurses' intention to
      stay from the perspective of cultural differences.
AB  - BACKGROUND: Culture has a great impact on human behavior; this is the key for
      organizational cultures in the Chinese society where relationships and hierarchy
      are emphasized and is especially exerted to the utmost by relationalism in
      Taiwan's collective society. PURPOSE: The purpose of this study was to explore
      the differences in the nature of preceptorship and functions between Eastern and
      Western cultures. METHODS: An exploratory research design was used. Qualitative
      field interviews were carried out with 20 new nurses who had worked in hospital
      settings for one year or less. RESULTS: In addition to the existing phases of a
      mentoring relationship, we drew out another preceptorship function dimension
      which represented the unique family ethics and superior-subordinate relationships
      in the Chinese nursing field and also added an important function, the quasi
      family functions to the mentoring. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: With
      the in-depth understanding of preceptorship in the Chinese culture, the
      development of localized teaching strategies for preceptors could effectively
      improve new nurses' job satisfaction and intention to stay and reduce their
      reality shock and role ambiguity.

PMID- 25614018
TI  - Bioinspired super-wettability from fundamental research to practical
      applications.
AB  - Engineered wettability is a traditional, yet key issue in surface science and
      attracts tremendous interest in solving large-scale practical problems. Recently,
      different super-wettability systems have been discovered in both nature and
      experiments. In this Review we present three types of super-wettability,
      including the three-dimensional, two-dimensional, and one-dimensional material
      surfaces. By combining different super-wettabilities, novel interfacial
      functional systems could be generated and integrated into devices for use in
      tackling current and the future problems including resources, energy,
      environment, and health. 

PMID- 25614020
TI  - Cognitive Profiles in Youth with Autism Spectrum Disorder: An Investigation of
      Base Rate Discrepancies using the Differential Ability Scales--Second Edition.
AB  - Extant data suggest that the cognitive profiles of individuals with ASD may be
      characterized by variability, particularly in terms of verbal intellectual
      functioning (VIQ) and non-verbal intellectual functioning (NVIQ) discrepancies.
      The Differential Ability Scales, Second Edition (DAS-II) has limited data
      available on its use with youth with ASD. The current study examined data from
      2,110 youth with ASD in order to characterize performance on the DAS-II and to
      investigate potential discrepancies between VIQ and NVIQ. A larger proportion of
      individuals in the ASD sample had significant discrepancies between VIQ and NVIQ
      when compared to the normative sample [early years sample chi2 (2) = 38.36; p <
      .001; school age sample chi2 (2) = 13.48; p < .01]. Clinical and research
      implications are discussed.

PMID- 25614019
TI  - Brief Report: Adaptive Functioning in Children with ASD, ADHD and ASD + ADHD.
AB  - Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder
      (ADHD) often co-occur. Children with ASD and ADHD demonstrate deficits in
      adaptive functioning, yet pure and comorbid groups have not been directly
      compared. Vineland Adaptive Behaviour Scales (VABS-II) data were examined in boys
      with ASD (n = 17), ADHD (n = 31) and ASD + ADHD (n = 38). Results demonstrated
      lower socialisation and composite scores and greater discrepancy between
      cognitive and adaptive abilities in the ASD + ADHD group compared to the ADHD
      only group. Significant associations were shown between reduced adaptive
      functioning and autism symptoms, but not ADHD symptoms. Children with ASD + ADHD
      present with exacerbated impairments in adaptive functioning relative to children
      with ADHD, associated with ASD symptoms. Disentangling variation in adaptive
      skills may aid the assessment of complex cases. 

PMID- 25614021
TI  - Brain computer interfaces for neurorehabilitation - its current status as a
      rehabilitation strategy post-stroke.
AB  - The idea of using brain computer interfaces (BCI) for rehabilitation emerged
      relatively recently. Basically, BCI for neurorehabilitation involves the
      recording and decoding of local brain signals generated by the patient, as he/her
      tries to perform a particular task (even if imperfect), or during a mental
      imagery task. The main objective is to promote the recruitment of selected brain
      areas involved and to facilitate neural plasticity. The recorded signal can be
      used in several ways: (i) to objectify and strengthen motor imagery-based
      training, by providing the patient feedback on the imagined motor task, for
      example, in a virtual environment; (ii) to generate a desired motor task via
      functional electrical stimulation or rehabilitative robotic orthoses attached to
      the patient's limb - encouraging and optimizing task execution as well as
      "closing" the disrupted sensorimotor loop by giving the patient the appropriate
      sensory feedback; (iii) to understand cerebral reorganizations after lesion, in
      order to influence or even quantify plasticity-induced changes in brain networks.
      For example, applying cerebral stimulation to re-equilibrate inter-hemispheric
      imbalance as shown by functional recording of brain activity during movement may
      help recovery. Its potential usefulness for a patient population has been
      demonstrated on various levels and its diverseness in interface applications
      makes it adaptable to a large population. The position and status of these very
      new rehabilitation systems should now be considered with respect to our current
      and more or less validated traditional methods, as well as in the light of the
      wide range of possible brain damage. The heterogeneity in post-damage expression
      inevitably complicates the decoding of brain signals and thus their use in
      pathological conditions, asking for controlled clinical trials.

PMID- 25614022
TI  - Comparison between tibial nerve block with anaesthetics and neurotomy in
      hemiplegic adults with spastic equinovarus foot.
AB  - OBJECTIVE: The aim of the study was to compare the effect of diagnostic motor
      nerve block with anaesthetics and of selective tibial neurotomy in the treatment
      of spastic equinovarus foot in hemiplegic adults. METHODS: In this prospective
      observational study, 30 hemiplegic adults with spastic equinovarus foot benefited
      from a diagnostic nerve block with anaesthetics followed by a selective tibial
      neurotomy performed at the level of the same motor nerve branches of the tibial
      nerve. Spasticity (Ashworth scale), muscle strength (Medical Research Council
      scale), passive ankle dorsiflexion (ROM), gait parameters (10 meters walking
      test) and gait kinematics (video assessment) were assessed before and after the
      nerve block and two months and two years after selective tibial neurotomy.
      RESULTS: The decrease in spasticity and the improvement in gait kinematics were
      similar after the diagnostic nerve block and two months and two years after
      neurotomy. The diagnostic nerve block did not revealed the slight increase in
      gait speed and in tibialis anterior muscle strength that was observed two years
      after neurotomy. CONCLUSION: This study suggests that diagnostic nerve block with
      anaesthetics and selective neurotomy equally reduce spasticity and improve gait
      in case of spastic equinovarus foot in hemiplegic adults. Diagnostic nerve block
      can be used as a valuable screening tool before neurotomy.

PMID- 25614023
TI  - Efficient bone formation in a swine socket lift model using Escherichia coli
      derived recombinant human bone morphogenetic protein-2 adsorbed in beta
      tricalcium phosphate.
AB  - Several preclinical studies have shown that Escherichia coli-derived bone
      morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone
      morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However,
      further investigation of the effectiveness and determination of the optimal
      dosage of E-BMP-2 in large animals are still necessary before its full
      application in humans. This study investigated the efficiency of different
      concentrations of E-BMP-2 adsorbed in beta-TCP for bone augmentation and
      osseointegration of immediate dental implants in a swine socket lift model.
      Following exposure of the maxillary sinus lateral wall, a 3.4-mm (diameter)
      cavity was drilled and filled with 0.1 g of beta-TCP containing different doses
      of E-BMP-2 (0, 10, 30, or 100 MUg/site) to lift the Schneiderian membrane. A
      dental implant was then immediately inserted. Bone-to-implant contact (BIC) and
      bone density (BD) examined via histological analysis were used as parameters to
      assess E-BMP-2 efficiency in bone formation. The implant stability quotient (ISQ)
      was measured using Osstell to determine the effect of E-BMP-2/beta-TCP on implant
      stability. After 8 weeks, the groups that received 30 and 100 MUg of E-BMP-2
      showed substantial new bone formation in the elevated space, while no bone
      formation was observed with beta-TCP alone. Accordingly, BIC and BD presented a
      dose-dependent response to increasing doses of E-BMP-2. However, there was no
      increase in implant stability with E-BMP-2 treatment. In conclusion, the E-BMP
      2/beta-TCP combination was efficient in bone formation and osseointegration of
      dental implants in a socket lift model in mini-pigs.

PMID- 25614024
TI  - Pictures of pain: their contribution to the neuroscience of empathy.
AB  - The study of empathy, a translation of the term 'Einfuhlung', originated in 19th
      century Germany in the sphere of aesthetics, and was followed by studies in
      psychology and then neuroscience. During the past decade the links between
      empathy and art have started to be investigated, but now from the neuroscientific
      perspective, and two different approaches have emerged. Recently, the primacy of
      the mirror neuron system and its association with automaticity and imitative,
      simulated movement has been envisaged. But earlier, a number of eminent art
      historians had pointed to the importance of cognitive responses to art; these
      responses might plausibly be subserved by alternative neural networks. Focusing
      here mainly on pictures depicting pain and evoking empathy, both approaches are
      considered by summarizing the evidence that either supports the involvement of
      the mirror neuron system, or alternatively suggests other neural networks are
      likely to be implicated. The use of such pictures in experimental studies
      exploring the underlying neural processes, however, raises a number of concerns,
      and suggests caution is exercised in drawing conclusions concerning the networks
      that might be engaged. These various networks are discussed next, taking into
      account the affective and sensory components of the pain experience, before
      concluding that both mirror neuron and alternative neural networks are likelyto
      be enlisted in the empathetic response to images of pain. A somewhat similar
      duality of spontaneous and cognitive processes may perhaps also be paralleled in
      the creation of such images. While noting that some have repudiated the
      neuroscientific approach to the subject, pictures are nevertheless shown here to
      represent an unusual but invaluable tool in the study of pain and empathy. 

PMID- 25614025
TI  - Molecular disorganization of axons adjacent to human lacunar infarcts.
AB  - Cerebral microvascular disease predominantly affects brain white matter and deep
      grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to
      white matter hyperintensities seen on magnetic resonance imaging. These lesions
      are common and result in both clinical stroke syndromes and accumulate over time,
      resulting in cognitive deficits and dementia. Magnetic resonance imaging studies
      suggest that these lesions progress over time, accumulate adjacent to prior
      lesions and have a penumbral region susceptible to further injury. The
      pathological correlates of this adjacent injury in surviving myelinated axons
      have not been previously defined. In this study, we sought to determine the
      molecular organization of axons in tissue adjacent to lacunar infarcts and in the
      regions surrounding microinfarcts, by determining critical elements in axonal
      function: the morphology and length of node of Ranvier segments and adjacent
      paranodal segments. We examined post-mortem brain tissue from six patients with
      lacunar infarcts and tissue from two patients with autosomal dominant retinal
      vasculopathy and cerebral leukoencephalopathy (previously known as hereditary
      endotheliopathy with retinopathy, nephropathy and stroke) who accumulate
      progressive white matter ischaemic lesions in the form of lacunar and
      microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of
      the infarct diameter away, both nodal and paranodal length increase by ~20% and
      80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling
      between axons and oligodendrocytes. Using premorbid magnetic resonance images,
      brain regions from patients with retinal vasculopathy and cerebral
      leukoencephalopathy that harboured periventricular white matter hyperintensities
      were selected and the molecular organization of axons was determined within these
      regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length
      in white matter of these patients is increased. Myelin basic protein and
      neurofilament immunolabelling demonstrates that axons in these adjacent regions
      have preserved axonal cytoskeleton organization and are generally myelinated.
      This indicates that the loss of normal axonal microdomain architecture results
      from disrupted axoglial signalling in white matter adjacent to lacunar and
      microinfarcts. The loss of the normal molecular organization of nodes and
      paranodes is associated with axonal degeneration and may lead to impaired
      conduction velocity across surviving axons after stroke. These findings
      demonstrate that the degree of white matter injury associated with cerebral
      microvascular disease extends well beyond what can be identified using imaging
      techniques and that an improved understanding of the neurobiology in these
      regions can drive new therapeutic strategies for this disease entity. 

PMID- 25614026
TI  - A novel TUBB4A mutation suggests that genotype-phenotype correlation of H-ABC
      syndrome needs to be revisited.

PMID- 25614028
TI  - Genetic and genomic analyses for economically important traits and their
      applications in molecular breeding of cultured fish.
AB  - The traits of cultured fish must continually be genetically improved to supply
      high-quality animal protein for human consumption. Economically important fish
      traits are controlled by multiple gene quantitative trait loci (QTL), most of
      which have minor effects, but a few genes may have major effects useful for
      molecular breeding. In this review, we chose relevant studies on some of the most
      intensively cultured fish and concisely summarize progress on identifying and
      verifying QTLs for such traits as growth, disease and stress resistance and sex
      in recent decades. The potential applications of these major-effect genes and
      their associated markers in marker-assisted selection and molecular breeding, as
      well as future research directions are also discussed. These genetic and genomic
      analyses will be valuable for elucidating the mechanisms modulating economically
      important traits and to establish more effective molecular breeding techniques in
      fish. 

PMID- 25614029
TI  - Fish genome manipulation and directional breeding.
AB  - Aquaculture is one of the fastest developing agricultural industries worldwide.
      One of the most important factors for sustainable aquaculture is the development
      of high performing culture strains. Genome manipulation offers a powerful method
      to achieve rapid and directional breeding in fish. We review the history of fish
      breeding methods based on classical genome manipulation, including polyploidy
      breeding and nuclear transfer. Then, we discuss the advances and applications of
      fish directional breeding based on transgenic technology and recently developed
      genome editing technologies. These methods offer increased efficiency, precision
      and predictability in genetic improvement over traditional methods. 

PMID- 25614027
TI  - Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1
      activities.
AB  - BACKGROUND: Human APOBEC3H (A3H) belongs to the A3 family of host restriction
      factors, which are cytidine deaminases that catalyze conversion of deoxycytidine
      to deoxyuridine in single-stranded DNA. A3 proteins contain either one (A3A, A3C,
      A3H) or two (A3B, A3D, A3F, A3G) Zn-binding domains. A3H has seven haplotypes (I
      VII) that exhibit diverse biological phenotypes and geographical distribution in
      the human population. Its single Zn-coordinating deaminase domain belongs to a
      phylogenetic cluster (Z3) that is different from the Z1- and Z2-type domains in
      other human A3 proteins. A3H HapII, unlike A3A or A3C, has potent activity
      against HIV-1. Here, we sought to identify the determinants of A3H HapII
      deaminase and antiviral activities, using site-directed sequence- and structure
      guided mutagenesis together with cell-based, biochemical, and HIV-1 infectivity
      assays. RESULTS: We have constructed a homology model of A3H HapII, which is
      similar to the known structures of other A3 proteins. The model revealed a large
      cluster of basic residues (not present in A3A or A3C) that are likely to be
      involved in nucleic acid binding. Indeed, RNase A pretreatment of 293T cell
      lysates expressing A3H was shown to be required for detection of deaminase
      activity, indicating that interaction with cellular RNAs inhibits A3H catalytic
      function. Similar observations have been made with A3G. Analysis of A3H deaminase
      substrate specificity demonstrated that a 5' T adjacent to the catalytic C is
      preferred. Changing the putative nucleic acid binding residues identified by the
      model resulted in reduction or abrogation of enzymatic activity, while
      substituting Z3-specific residues in A3H to the corresponding residues in other
      A3 proteins did not affect enzyme function. As shown for A3G and A3F, some A3H
      mutants were defective in catalysis, but retained antiviral activity against HIV
      1vif (-) virions. Furthermore, endogenous reverse transcription assays
      demonstrated that the E56A catalytic mutant inhibits HIV-1 DNA synthesis,
      although not as efficiently as wild type. CONCLUSIONS: The molecular and
      biological activities of A3H are more similar to those of the double-domain A3
      proteins than to those of A3A or A3C. Importantly, A3H appears to use both
      deaminase-dependent and -independent mechanisms to target reverse transcription
      and restrict HIV-1 replication.

PMID- 25614030
TI  - Germ cells from pluripotent stem cells: mouse versus human.

PMID- 25614031
TI  - Near-atomic resolution structure of the largest known Ca(2+) channel: ryanodine
      receptor.

PMID- 25614032
TI  - Calcifications in benfluorex-induced valve heart disease: a misknown association.
AB  - Benfluorex, an anorexigenic agent, is recognized to induce noncalcified
      restrictive valvular regurgitation. We report a well-documented case of a 73-year
      old patient who developed heart failure with aortic and mitral regurgitation
      following benfluorex intake. Echocardiography and peroperative analysis found
      large mitral annular calcifications and aortic subvalvular calcifications.
      Pathology confirmed drug-induced valve heart disease (DIVHD). The presence of
      valvular apparatus calcification should not lead to diagnosis of degenerative
      valvular disease and a priori preclude the diagnosis of DIVHD.

PMID- 25614037
TI  - Computational design of novel peptidomimetic inhibitors of cadherin homophilic
      interactions.
AB  - We report a first set of peptidomimetic ligands mimicking the adhesive interface
      identified by recent crystallographic structures of E- and N-cadherin. Compounds
      2 and 3 inhibit adhesion of epithelial ovarian cancer (EOC) cells with improved
      efficacy compared to the ADH-1 peptide, a N-cadherin antagonist that is in early
      clinical trials in EOC patients.

PMID- 25614038
TI  - Severe growth hormone deficiency and empty sella in obesity: a cross-sectional
      study.
AB  - Obesity is associated with blunted growth hormone (GH) secretion. In some
      individuals, hypothalamic-pituitary (HP) structural lesions may contribute to GH
      deficiency (GHD). We explored pituitary morphology in obese patients with
      suspected GHD and its association with cardiovascular risk factors, body
      composition, and cardiac morphology. One hundred and eighty-four adults obese
      patients with symptoms and signs of GHD (147 females and 37 males; mean age 46.31
      +/- 12.11 years), out of 906 consecutive white obese outpatients, were evaluated.
      The main measures were anthropometric data, blood pressure, lipid profile,
      glycemic parameters, pituitary hormones, and insulin-like growth factor-1 values,
      echocardiography, magnetic resonance imaging (MRI) of the HP region, body
      composition, and growth hormone-releasing hormone plus arginine test. Seventy
      patients had GHD (GH peak values <4.2 MUg/mL). GHD patients showed significantly
      higher body mass index and fat mass, lower lumbar bone mineral density, increased
      left ventricular mass index, and epicardial fat thickness. The MRI of the HP
      region showed empty sella (ES) in 69 and normal pituitary in one of the 70 GHD
      patients; the 114 patients with normal GH response had ES (n = 62, 54 %), normal
      pituitary (n = 37, 32 %), microadenomas (n = 10, 8 %), and other pituitary
      abnormalities (n = 5, 4 %). ES was a significant independent predictor of GH
      secretory capacity as determined by multiple regression analysis. The close
      relationship between ES and GH secretory capacity points out to the possibility
      of the organic nature of GHD in a portion of obese individuals and opens a new
      scenario with regard to the potential of GH treatment on metabolic consequences
      of obesity.

PMID- 25614039
TI  - Association of urinary sodium/creatinine ratio with bone mineral density in
      postmenopausal women: KNHANES 2008-2011.
AB  - Accumulating evidence shows that high sodium chloride intake increases urinary
      calcium excretion and may be a risk factor for osteoporosis. However, the effect
      of oral sodium chloride intake on bone mineral density (BMD) and risk of
      osteoporosis has been inadequately researched. The aim of the present study was
      to determine whether urinary sodium excretion (reflecting oral sodium chloride
      intake) associates with BMD and prevalence of osteoporosis in postmenopausal
      women. This cross-sectional study involved a nationally representative sample
      consisting of 2,779 postmenopausal women who participated in the Korea National
      Health and Nutritional Examination Surveys in 2008-2011. The association of
      urinary sodium/creatinine ratio with BMD and other osteoporosis risk factors was
      assessed. In addition, the prevalence of osteoporosis was assessed in four groups
      with different urinary sodium/creatinine ratios. Participants with osteoporosis
      had significantly higher urinary sodium/creatinine ratios than the participants
      without osteoporosis. After adjusting for multiple confounding factors, urinary
      sodium/creatinine ratio correlated inversely with lumbar spine BMD (P = 0.001).
      Similarly, when participants were divided into quartile groups according to
      urinary sodium/creatinine ratio, the average BMD dropped as the urinary
      sodium/creatinine ratio increased. Multiple logistic regression analysis revealed
      that compared to quartile 1, quartile 4 had a significantly increased prevalence
      of lumbar spine osteoporosis (odds ratios 1.346, P for trend = 0.044). High
      urinary sodium excretion was significantly associated with low BMD and high
      prevalence of osteoporosis in lumbar spine. These results suggest that high
      sodium chloride intake decreases lumbar spine BMD and increases the risk of
      osteoporosis in postmenopausal women.

PMID- 25614040
TI  - Low testosterone and non-alcoholic fatty liver disease: Evidence for their
      independent association in men with chronic spinal cord injury.
AB  - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver
      phenotype of metabolic syndrome, which in turn is associated with male
      hypogonadism. We assessed whether an independent association between NAFLD and
      androgen deficiency could be revealed in men with chronic spinal cord injury
      (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a
      combination of risk factors for metabolic syndrome. DESIGN: Fifty-five
      consecutive men with chronic SCI admitted to a rehabilitation program underwent
      clinical/biochemical evaluations and liver ultrasonography. RESULTS: NAFLD was
      diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited
      significantly higher body mass index, Homeostatic model assessment of insulin
      resistance, triglycerides and gamma-glutamyl transpeptidase values, lower total
      and free testosterone levels and they were engaged in a significantly poorer
      weekly leisure time physical activity (LTPA). At the multiple logistic regression
      analysis, only total and free testosterone levels exhibited a significant
      independent association with NAFLD. The risk of having NAFLD increased indeed of
      1% for each decrement of 1 ng/dL of total testosterone and of 3% for each
      decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In
      men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached
      85%: they had a risk of having NAFLD significantly higher (~12-fold) than those
      with total testosterone >= 300 ng/dL, after adjustment for confounders.
      CONCLUSION: The evidence of an independent association between NAFLD and low
      testosterone is strongly reinforced by its demonstration in men with chronic SCI,
      in spite of the many confounders peculiar to this population.

PMID- 25614042
TI  - Prospective association of vitamin D with frailty status and all-cause mortality
      in older adults: Results from the KORA-Age Study.
AB  - OBJECTIVE: To assess the prospective association of serum 25-hydroxyvitamin D
      [25(OH)D] levels with frailty status and all-cause mortality in a cohort of
      community-dwelling participants of the population-based KORA [Cooperative Health
      Research in the Region of Augsburg]-Age Study. METHODS: 727 non-frail
      participants, aged >=65years, with 25(OH)D measurement at baseline in 2009, were
      followed for 2.9+/-0.1years. Participants were classified as pre-frail or frail
      if they met 1-2 or >=3, respectively, of the following five criteria: weight
      loss, exhaustion, physical inactivity, low walking speed, weakness. The
      association between 25(OH)D and mortality was assessed in 954 participants.
      Multivariable adjusted logistic regression models were calculated for each
      outcome. RESULTS: The incidence of pre-frailty and frailty was 21.2% and 3.9%
      respectively. After multivariable adjustment, participants with very low 25(OH)D
      levels (<15ng/ml vs. >=30ng/ml) had a significantly higher odds for pre-frailty
      (OR=2.43 [95% CI: 1.17-5.03]) and pre-frailty/frailty combined (OR=2.53 [95% CI:
      1.23-5.22]), but not for frailty alone (OR=2.63 [95% CI: 0.39-17.67]). The
      association between 25(OH)D and mortality (OR=3.39 [95% CI: 1.08-10.65]) was
      partly mediated by frailty status. CONCLUSION: Very low 25(OH)D levels were
      independently associated with incident pre-frailty, pre-frailty/frailty combined
      and all-cause mortality.

PMID- 25614043
TI  - An evaluation of the association between an antimicrobial stewardship score and
      antimicrobial usage.
AB  - OBJECTIVES: To determine whether an antimicrobial stewardship 'intensity' score
      predicts hospital antimicrobial usage. METHODS: An antimicrobial stewardship
      score for 44 academic medical centres was developed that comprised two main
      categories: resources (antimicrobial stewardship programme personnel and
      automated surveillance software) and strategies (preauthorization, audit with
      intervention and feedback, education, guidelines and clinical pathways,
      parenteral to oral therapy programmes, de-escalation of therapy, antimicrobial
      order forms and dose optimization). Multiple regression analyses were used to
      assess whether the composite score and also the categories were associated with
      either total or antimicrobial stewardship programme-target antimicrobial use as
      measured in days of therapy. RESULTS: The mean antimicrobial stewardship
      programme score was 55 (SD 21); the total composite score was not significantly
      associated with total or target antimicrobial use [estimate -0.49 (95% CI -2.30
      to 0.89)], while the category strategies was significantly and negatively
      associated with target antimicrobial use [-5.91 (95% CI -9.51 to -2.31)].
      CONCLUSIONS: The strategy component of a score developed to measure the intensity
      of antimicrobial stewardship was associated with the amount of antimicrobials
      used. Thus, the number and types of strategies employed by antimicrobial
      stewardship programmes may be of particular importance in programme
      effectiveness.

PMID- 25614041
TI  - Regulation of cancer metastasis by microRNAs.
AB  - MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that have been
      found highly conserved among species. MiRNAs are able to negatively regulate gene
      expression through base pairing of 3' UTRs of their target genes. Therefore,
      miRNAs have been shown to play an important role in regulating various cellular
      activities. Over the past decade, substantial evidences have been obtained to
      show that miRNAs are aberrantly expressed in human malignancies and could act as
      "OncomiRs" or "Tumor suppressor miRs". In recent years, increasing number of
      studies have demonstrated the involvement of miRNAs in cancer metastasis. Many
      studies have shown that microRNAs could directly target genes playing a central
      role in epithelia-mesenchymal-transition (EMT), a cellular transformation process
      that allows cancer cells to acquire motility and invasiveness. EMT is considered
      an essential step driving the early phase of cancer metastasis. This review will
      summarize the recent findings and characterization of miRNAs that are involved in
      the regulation of EMT, migration, invasion and metastasis of cancer cells.
      Lastly, we will discuss potential use of miRNAs as diagnostic and prognostic
      biomarkers as well as therapeutic targets for cancer. 

PMID- 25614044
TI  - Comparative effectiveness of cefazolin versus cloxacillin as definitive
      antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort
      study.
AB  - OBJECTIVES: We compared the effectiveness of cefazolin versus cloxacillin in the
      treatment of MSSA bacteraemia in terms of mortality and relapse. METHODS: A
      retrospective cohort study examined consecutive patients with Staphylococcus
      aureus bacteraemia from six academic and community hospitals between 2007 and
      2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the
      predominant definitive antibiotic therapy were included in the study. Ninety-day
      mortality was compared between the two groups matched by propensity scores.
      RESULTS: Of 354 patients included in the study, 105 (30%) received cefazolin and
      249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days,
      96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in
      the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S.
      aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the
      cloxacillin group. All relapses in the cefazolin group were related to a deep
      seated infection. Based on the estimated propensity score, 90 patients in the
      cefazolin group were matched with 90 patients in the cloxacillin group. In the
      propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31-1.08, P
      = 0.0846) for 90 day mortality. CONCLUSIONS: There was no significant clinical
      difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia
      with respect to mortality. Cefazolin was associated with non-significantly more
      relapses compared with cloxacillin, especially in deep-seated S. aureus
      infections.

PMID- 25614045
TI  - Improved detection of resistance at failure to a tenofovir, emtricitabine and
      efavirenz regimen by ultradeep sequencing.
AB  - OBJECTIVES: Resistant minority variants present before ART can be a source of
      virological failure. This has been shown for NRTIs, NNRTIs and CCR5 inhibitors.
      However, very few data are available for the detection of such minority resistant
      variants that could be selected at virological failure and not detected using
      classical Sanger sequencing. METHODS: We studied 26 patients treated with
      tenofovir, emtricitabine and efavirenz with their first virological failure
      (defined as two consecutive viral loads >50 copies/mL). We performed standard
      Sanger sequencing and ultradeep sequencing (UDS; Roche 454((r)) Life Sciences) in
      plasma at failure. For UDS, mutations >1% were considered. We compared the
      presence of reverse transcriptase mutations between the two techniques, using the
      latest ANRS algorithm. RESULTS: UDS detected more resistance mutations in 38.5%
      of cases (10/26 patients) and the genotypic sensitivity score (GSS) was reduced
      for 6 of them (23.1%). The GSS was impacted more often for NRTIs than for NNRTIs,
      for which most mutations were already detected by Sanger sequencing. Resistant
      minority variants were detected even in patients with low viral load at failure.
      CONCLUSIONS: These results strongly argue for the use of next-generation
      sequencing in patients failing on an NRTI+NNRTI regimen, as UDS has the potential
      to modify the choice of the subsequent regimen.

PMID- 25614046
TI  - Insolation driven biomagnetic response to the Holocene Warm Period in semi-arid
      East Asia.
AB  - The Holocene Warm Period (HWP) provides valuable insights into the climate system
      and biotic responses to environmental variability and thus serves as an excellent
      analogue for future global climate changes. Here we document, for the first time,
      that warm and wet HWP conditions were highly favourable for magnetofossil
      proliferation in the semi-arid Asian interior. The pronounced increase of
      magnetofossil concentrations at ~9.8 ka and decrease at ~5.9 ka in Dali Lake
      coincided respectively with the onset and termination of the HWP, and are
      respectively linked to increased nutrient supply due to postglacial warming and
      poor nutrition due to drying at ~6 ka in the Asian interior. The two-stage
      transition at ~7.7 ka correlates well with increased organic carbon in middle HWP
      and suggests that improved climate conditions, leading to high quality nutrient
      influx, fostered magnetofossil proliferation. Our findings represent an excellent
      lake record in which magnetofossil abundance is, through nutrient availability,
      controlled by insolation driven climate changes.

PMID- 25614047
TI  - Ultrasound-guided therapeutic focused ultrasound: current status and future
      directions.
AB  - This paper reviews ultrasound imaging methods for the guidance of therapeutic
      focused ultrasound (USgFUS), with emphasis on real-time preclinical methods.
      Guidance is interpreted in the broadest sense to include pretreatment planning,
      siting of the FUS focus, real-time monitoring of FUS-tissue interactions, and
      real-time control of exposure and damage assessment. The paper begins with an
      overview and brief historical background of the early methods used for monitoring
      FUS-tissue interactions. Current imaging methods are described, and discussed in
      terms of sensitivity and specificity of the localisation of the FUS effects in
      both therapeutic and sub-therapeutic modes. Thermal and non-thermal effects are
      considered. These include cavitation-enhanced heating, tissue water boiling and
      cavitation. Where appropriate, USgFUS methods are compared with similar methods
      implemented using other guidance modalities, e.g. magnetic resonance imaging.
      Conclusions are drawn regarding the clinical potential of the various guidance
      methods, and the feasibility and current status of real-time implementation. 

PMID- 25614048
TI  - Prostaglandin F2alpha induces expression of activating transcription factor 3
      (ATF3) and activates MAPK signaling in the rat corpus luteum.
AB  - The current study was conducted to evaluate the expression of ATF3, in
      association with the activation of mitogen-activated protein kinases (MAPK)
      during prostaglandin F2alpha analog (PGF)-induced luteal regression in rats. A
      sequential PMSG/hCG treatment paradigm was used to obtain a single, well-defined
      generation of corpora lutea (CL) in rats. Rats were treated with PGF for 0-4h on
      day 7 of pseudopregnancy. Results showed that serum progesterone (P4)
      concentrations declined in a time dependent manner. Western blot results revealed
      that ATF3 increased within 2h post-PGF injection. Phosphorylated ERK1/2 (p-ERK)
      and JNK (p-JNK) increased within 30min and then were gradually reduced in
      response to PGF. In contrast, the levels of phosphorylated p38 MAPK (p-p38) were
      not significantly altered. The immunostaining density for p-ERK decreased from
      the periphery to the center of the corpus luteum following treatment with PGF,
      while ATF3 was expressed uniformly in the nuclei of luteal steroidogenic cells.
      These results indicated that treatment with PGF in vivo could induce increases in
      MAPK phosphorylation, especially in p-ERK, which might be correlated with the
      increases in ATF3 expression and the decline in P4 concentrations. To our
      knowledge, this is the first study to provide evidence for temporal relationships
      between MAPK activation and ATF3 expression during PGF-induced luteal regression
      in the rat. 

PMID- 25614049
TI  - Homophobia and communal coping for HIV risk management among gay men in
      relationships.
AB  - Men who have sex with men (MSM) remain disproportionately affected by the HIV
      epidemic in the US and estimates suggest that one to two-thirds of new infections
      occur among main partners. Previous research has focused on individual MSM and
      their risk for HIV, yet couples' ability to manage risk has been largely
      understudied. In particular, the role that homophobia plays in shaping the
      ability of gay male couples to cope with HIV risk is currently understudied. A
      sample of 447 gay/bisexual men with main partners was taken from a 2011 survey of
      gay and bisexual men in Atlanta. Linear regression models were fitted for three
      couples' coping outcome scales (outcome efficacy, couple efficacy, communal
      coping) and included indicators of homophobia (internalized homophobia and
      homophobic discrimination). Findings indicate that reporting of increased levels
      of internalized homophobia were consistently associated with decreased outcome
      measures of couples' coping ability regarding risk management. The results
      highlight the role that homophobia plays in gay male couples' relationships and
      HIV risk, extending the existing literature in the field of same-sex
      relationships as influenced by homophobia. 

PMID- 25614051
TI  - Integrating autophagy and metabolism in cancer.
AB  - Autophagy is a catabolic process mediated by lysosomal degradation and is a key
      player in regulating cellular metabolism during cancer progression. Autophagy
      maintains cellular homeostasis by degrading unnecessary cellular molecules, which
      also prevents tumorigenesis. Conversely, autophagy also provides nutrients that
      support malignant tumor growth in advanced tumors. Multiple novel mechanisms have
      been proposed to explain the tumor-facilitating role of autophagy. Autophagy
      regulates diverse metabolic pathways that promote tumor proliferation and
      survival, which are closely associated with oncogenic activators and tumor
      suppressors. Autophagy has been implicated in cancer cell invasion and
      metastasis. Accordingly, autophagy has emerged as a tumor-promoting mechanism
      that facilitates cancer cell growth and survival. Mechanistic studies of
      autophagy during tumor progression may identify potential targets that can be
      utilized to disrupt cancer development. Understanding the molecular networks
      integrating metabolic changes and autophagy in cancer cells could provide novel
      insights to enhance targeted cancer therapies. 

PMID- 25614050
TI  - Psychological symptoms are associated with both abstinence and risky sex among
      men with HIV.
AB  - Sexual abstinence is often deemed the "safest behavior" in HIV prevention, but is
      sometimes associated with psychological symptoms (e.g., depression) just as
      sexually risky behavior is. This study explored whether sexual abstinence and
      risky sexual behavior among men with HIV were associated with similar
      constellations of psychological symptoms. Prior research has not addressed this
      issue because abstinent people often are not included in the sample or, when data
      are analyzed, researchers combine abstinent people with sexually active people
      who practice safer sex. Past research also neglects the co-morbidity of
      psychological symptoms. A latent class analysis of the psychological symptoms
      (assessed with the Symptom Check List 90-R; Derogatis, 1994) of 140 men with HIV,
      mostly from rural New England, revealed three latent classes: men who were
      asymptomatic on all symptom domains (28.8 %), men who were symptomatic on all
      domains (34.1 %), and men who were symptomatic on internalizing domains (37.1 %),
      but were asymptomatic on the externalizing symptoms of hostility and paranoid
      ideation. Logistic regression showed that sexual behavior during the past 90 days
      of men in the all symptom class and the internalizing symptoms class was similar,
      with abstinence and risky sex predominating, and safer sex being relatively
      uncommon for both classes. The sexual behavior of men in the asymptomatic class
      differed, with safer sex being relatively more likely to occur compared to the
      symptomatic classes. These findings suggest that the psychological symptom
      profile of sexually abstinent people places them at risk for inconsistent condom
      use should they engage in sexual behavior. 

PMID- 25614053
TI  - Editorial comment to International Prostate Symptom Score is a predictive factor
      of lower urinary tract symptoms after radical prostatectomy.

PMID- 25614052
TI  - Standard operating procedures for standardized mass rearing of the dengue and
      chikungunya vectors Aedes aegypti and Aedes albopictus (Diptera: Culicidae) - I -
      egg quantification.
AB  - BACKGROUND: Quantification of eggs prior to rearing the immature stages of
      mosquitoes is an essential step in establishing a standardized mass rearing
      system. To develop a simple and accurate method of egg quantification for Aedes
      aegypti and Aedes albopictus, the relationship between egg number and weight, as
      well as egg number and volume, were studied. METHODS: Known quantities of eggs
      (1,000, 3,000, 6,000, 12,000, 15,000, 18,000, 21,000 and 27,000) were counted and
      subsequently their weight and volume were measured. Best-fit curves and
      regression equations were used to describe relationships between Aedes egg number
      and both weight and volume. RESULTS: Eighteen thousand Ae. aegypti eggs weighed
      159.8 mg and had a volume of 277.4 MUl, compared to measurements of 131.5 mg and
      230.3 MUl for Ae. albopictus. The eggs of Ae. aegypti were thus larger and
      heavier than those of Ae. albopictus. The use of weight and volume to quantify
      egg number was validated by counting volumes and weights of eggs expected to
      correspond to 3,000 and 18,000 eggs of each species; significant correlations
      were found in all cases except in the case of 3,000 Ae. albopictus eggs measured
      by volume. CONCLUSION: Methods for egg quantification were validated and shown to
      be a consistent and practical means to achieve uniform distribution of Aedes
      larvae between rearing trays, important for optimal mass rearing of the immature
      stages of Aedes mosquitoes.

PMID- 25614054
TI  - The effect of age on coordination of stabilization during changing environmental
      dynamics.
AB  - Coordination as part of the stabilization process of joints is compromised in
      older adults. We addressed changes in neuromuscular control and force output
      during a ballistic force production task influenced by different environmental
      dynamics. Aged participants (AP) and young participants (YP) were asked to
      perform a unilateral maximal leg extension against a movable sled in a reaction
      time task. The task was performed in a sitting posture and involved a stable (1
      degree of freedom; DoF) or an unstable (3 DoF) condition of the sled.
      Electromyographic and dynamometric recordings were made and analyzed using the
      cross-correlation-function, assessment of peak EMG-activity and peak force.
      Initial motor strategies (i.e. motor system adjustments in order to meet the
      demands of the particular task while respecting individual constraints) were
      assessed by analyzing total reaction times (TRT), premotor time (PMT) and
      electromechanical delay (EMD). The AP group showed motor control strategies
      governed by prolonged TRT in both conditions. However, the change of mechanical
      interactions (i.e. the interaction between the participant and the sled in its
      particular mechanical state) caused group specific motor system adjustments in
      PMT and EMD. Force measures showed reduced peak forces in AP accompanied by less
      loss of force between conditions compared to YP. Inter- and intramuscular
      coordination strategies differed between YP and AP reflected in changes in CCF
      and peak EMG values. We conclude that change in environmental dynamics is
      associated with specific adjustments of control properties of the motor system.
      These adjustments were sensitive to age and mechanical condition (1 or 3 DoF) and
      might contribute to declines in motor output seen in AP. However, due to the
      nature of the task, our results do not allow a direct transfer to situations
      involving whole body balance. 

PMID- 25614055
TI  - Comments on Efendijev et al.: temporal trends in cardiac arrest incidence and
      outcome in Finnish intensive care units from 2003 to 2013.

PMID- 25614056
TI  - From the intensive care bed: we need to hear and listen.

PMID- 25614057
TI  - The incidence and outcome of in-ICU cardiac arrest.

PMID- 25614058
TI  - My paper 20 years later: cerebral venous oxygen saturation studied with bilateral
      samples in the internal jugular veins.
AB  - INTRODUCTION: Jugular oxygen saturation monitoring was introduced in
      neurointensive care after severe traumatic brain injury (TBI) to explore the
      adequacy of brain perfusion and guide therapeutic interventions. The brain was
      considered homogeneous, and oxygen saturation was taken as representative of the
      whole organ. We investigated whether venous outflow from the brain was
      homogeneous by measuring oxygen saturation simultaneously from the two jugular
      veins. METHODS: In 32 comatose TBI patients both internal jugular veins (IJs)
      were simultaneously explored using intermittent samples; hemoglobin saturation
      was also recorded continuously by fiber-optic catheters in five patients. In five
      cases long catheters were inserted bilaterally upstream, up to the sigmoid
      sinuses. MAIN FINDINGS: On average, measurements from the two sides were in
      agreement (mean and standard deviation of the differences between the saturation
      of the two IJs were respectively 5.32 and 5.15). However, 15 patients showed
      differences of more than 15 % in hemoglobin saturation at some point; three
      others showed differences larger than 10 %. No relationship was found between the
      computed tomographic scan data and the hemoglobin saturation pattern.
      DISCUSSION/CONCLUSION: Several groups have confirmed differences between oxygen
      saturation in the two jugular veins. After years of enthusiasm, interest for
      jugular saturation has decreased and more modern methods, such as tissue
      oxygenation monitoring, are now available. Jugular saturation monitoring has low
      sensitivity, with the risk of missing low saturation, but high specificity;
      moreover it is cheap, when used with intermittent sampling. Monitoring the
      adequacy of brain perfusion after severe TBI is essential. However the choice of
      a specific monitor depends on local resources and expertise.

PMID- 25614059
TI  - Protective effects of Millettia pulchra flavonoids on myocardial ischemia in
      vitro and in vivo.
AB  - BACKGROUND: Previous studies have demonstrated that Millettia pulchra flavonoids
      (MPF) exhibit protective effects on myocardial ischemia reperfusion injury
      (MI/RI) in isolated rat hearts and show anti-oxidative, anti-hypoxic and anti
      stress properties. METHODS: In this study, the cardioprotective effects of MPF on
      myocardial ischemia and its underlying mechanisms were investigated by a hypoxia/
      reoxygenation (H/R) injury model in vitro and a rat MI/RI model in vivo. RESULTS:
      We found that the lactate dehydrogenase (LDH) and inducible nitric oxide synthase
      (iNOS) activities were decreased in the MPF pretreatment group, whereas the
      activities of constructional nitric oxide synthase (cNOS), total nitric oxide
      synthase (tNOS), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were significantly
      increased. In addition, the cardiocytes were denser in the MPF groups than in the
      control group. The mortality rate and apoptosis rate of cardiocytes were
      significantly decreased. Furthermore, pretreatment with MPF in vivo significantly
      improved the hemodynamics, decreased malondialdehyde (MDA) abundance, increased
      the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px) and decreased the expression of the Bax protein and ratio Bax/Bc1-2
      ration. CONCLUSIONS: These results suggest that MPF is an attractive protective
      substance in myocardial ischemia due to its negative effects on heart rate and
      ionotropy, reduction of myocardial oxidative damage and modulation of gene
      expression associated with apoptosis.

PMID- 25614060
TI  - Liposomal bupivacaine in forefoot surgery.
AB  - BACKGROUND: Liposomal bupivacaine is increasingly being utilized in attempts to
      provide prolonged local analgesia in the immediate postoperative period. The
      purpose of this study was to quantify the reduction in opioid consumption as well
      as postoperative pain scores in the postoperative period when liposomal
      bupivacaine is used at the conclusion of forefoot surgery. METHODS: This was a
      prospective therapeutic cohort study with 20 patients receiving liposomal
      bupivacaine at the conclusion of their forefoot procedure in addition to our
      routine multimodal analgesic protocol and 20 patients as the control without the
      addition of liposomal bupivacaine. Pain scores, number of narcotic pills consumed
      on postoperative days 1 through 4, need for refill, time to first refill and
      wound complications were evaluated. RESULTS: Mean number of narcotic pills
      consumed on postoperative day 1 (1.4 vs 3.6, P = .002) and day 2 (1.8 vs 3.6, P =
      .021) was significantly lower for the liposomal bupivacaine group than the
      control group. Daily pain scores were lower for those patients who received
      liposomal bupivacaine on postoperative days 1 through 4, although this was not
      statistically significant. Fewer patients required medication refills in the
      liposomal bupivacaine group compared to the control group, however this was not
      statistically significant (3 vs 7, P = .273). There was no increase in wound
      complications in the liposomal bupivacaine group when compared to the control (1
      vs 4). CONCLUSION: Liposomal bupivacaine appears to be a useful adjunct in the
      treatment of postoperative pain when used as a part of a multimodal analgesic
      regimen in patients undergoing forefoot surgery. LEVEL OF EVIDENCE: Level II,
      prospective comparative study.

PMID- 25614061
TI  - Physiologically based pharmacokinetic model for 6-mercpatopurine: exploring the
      role of genetic polymorphism in TPMT enzyme activity.
AB  - AIMS: To extend the physiologically based pharmacokinetic (PBPK) model developed
      for 6-mercaptopurine to account for intracellular metabolism and to explore the
      role of genetic polymorphism in the TPMT enzyme on the pharmacokinetics of 6
      mercaptopurine. METHODS: The developed PBPK model was extended for 6
      mercaptopurine to account for intracellular metabolism and genetic polymorphism
      in TPMT activity. System and drug specific parameters were obtained from the
      literature or estimated using plasma or intracellular red blood cell
      concentrations of 6-mercaptopurine and its metabolites. Age-dependent changes in
      parameters were implemented for scaling, and variability was also introduced for
      simulation. The model was validated using published data. RESULTS: The model was
      extended successfully. Parameter estimation and model predictions were
      satisfactory. Prediction of intracellular red blood cell concentrations of 6
      thioguanine nucleotide for different TPMT phenotypes (in a clinical study that
      compared conventional and individualized dosing) showed results that were
      consistent with observed values and reported incidence of haematopoietic
      toxicity. Following conventional dosing, the predicted mean concentrations for
      homozygous and heterozygous variants, respectively, were about 10 times and two
      times the levels for wild-type. However, following individualized dosing, the
      mean concentration was around the same level for the three phenotypes despite
      different doses. CONCLUSIONS: The developed PBPK model has been extended for 6
      mercaptopurine and can be used to predict plasma 6-mercaptopurine and tissue
      concentration of 6-mercaptopurine, 6-thioguanine nucleotide and 6
      methylmercaptopurine ribonucleotide in adults and children. Predictions of
      reported data from clinical studies showed satisfactory results. The model may
      help to improve 6-mercaptopurine dosing, achieve better clinical outcome and
      reduce toxicity.

PMID- 25614062
TI  - Revealing shared and distinct gene network organization in Arabidopsis immune
      responses by integrative analysis.
AB  - Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) are two
      main plant immune responses to counter pathogen invasion. Genome-wide gene
      network organizing principles leading to quantitative differences between PTI and
      ETI have remained elusive. We combined an advanced machine learning method and
      modular network analysis to systematically characterize the organizing principles
      of Arabidopsis (Arabidopsis thaliana) PTI and ETI at three network resolutions.
      At the single network node/edge level, we ranked genes and gene interactions
      based on their ability to distinguish immune response from normal growth and
      successfully identified many immune-related genes associated with PTI and ETI.
      Topological analysis revealed that the top-ranked gene interactions tend to link
      network modules. At the subnetwork level, we identified a subnetwork shared by
      PTI and ETI encompassing 1,159 genes and 1,289 interactions. This subnetwork is
      enriched in interactions linking network modules and is also a hotspot of attack
      by pathogen effectors. The subnetwork likely represents a core component in the
      coordination of multiple biological processes to favor defense over development.
      Finally, we constructed modular network models for PTI and ETI to explain the
      quantitative differences in the global network architecture. Our results indicate
      that the defense modules in ETI are organized into relatively independent
      structures, explaining the robustness of ETI to genetic mutations and effector
      attacks. Taken together, the multiscale comparisons of PTI and ETI provide a
      systems biology perspective on plant immunity and emphasize coordination among
      network modules to establish a robust immune response. 

PMID- 25614063
TI  - SUMOylation by a stress-specific small ubiquitin-like modifier E2 conjugase is
      essential for survival of Chlamydomonas reinhardtii under stress conditions.
AB  - Posttranslational modification of proteins by small ubiquitin-like modifier
      (SUMO) is required for survival of virtually all eukaryotic organisms. Attachment
      of SUMO to target proteins is catalyzed by SUMO E2 conjugase. All haploid or
      diploid eukaryotes studied to date possess a single indispensable SUMO conjugase.
      We report here the unanticipated isolation of a Chlamydomonas reinhardtii
      (mutant5 [mut5]). in which the previously identified SUMO conjugase gene C.
      reinhardtii ubiquitin-conjugating enzyme9 (CrUBC9) is deleted. This surprising
      mutant is viable and unexpectedly, displays a pattern of protein SUMOylation at
      25 degrees C that is essentially identical to wild-type cells. However, unlike
      wild-type cells, mut5 fails to SUMOylate a large set of proteins in response to
      multiple stress conditions, a failure that results in a markedly reduced
      tolerance or complete lack of tolerance to these stresses. Restoration of
      expected stress-induced protein SUMOylation patterns as well as normal stress
      tolerance phenotypes in mut5 cells complemented with a CrUBC9 gene shows that
      CrUBC9 is an authentic SUMO conjugase and, more importantly, that SUMOylation is
      essential for cell survival under stress conditions. The presence of bona fide
      SUMOylated proteins in the mut5 mutant at 25 degrees C can only be explained by
      the presence of at least one additional SUMO conjugase in C. reinhardtii, a
      conjugase tentatively identified as CrUBC3. Together, these results suggest that,
      unlike all other nonpolyploid eukaryotes, there are at least two distinct and
      functional SUMO E2 conjugases in C. reinhardtii, with a clear division of labor
      between the two sets: One (CrUBC9) is involved in essential stress-induced
      SUMOylations, and one (CrUBC3) is involved in housekeeping SUMOylations.

PMID- 25614064
TI  - Two distinct families of protein kinases are required for plant growth under high
      external Mg2+ concentrations in Arabidopsis.
AB  - Protein phosphorylation events play key roles in maintaining cellular ion
      homeostasis in higher plants, and the regulatory roles of these events in Na(+)
      and K(+) transport have been studied extensively. However, the regulatory
      mechanisms governing Mg(2+) transport and homeostasis in higher plants remain
      poorly understood, despite the vital roles of Mg(2+) in cellular function. A
      member of subclass III sucrose nonfermenting-1-related protein kinase2 (SnRK2),
      SRK2D/SnRK2.2, functions as a key positive regulator of abscisic acid (ABA)
      mediated signaling in response to water deficit stresses in Arabidopsis
      (Arabidopsis thaliana). Here, we used immunoprecipitation coupled with liquid
      chromatography-tandem mass spectrometry analyses to identify Calcineurin B-like
      interacting protein kinase26 (CIPK26) as a novel protein that physically
      interacts with SRK2D. In addition to CIPK26, three additional CIPKs (CIPK3,
      CIPK9, and CIPK23) can physically interact with SRK2D in planta. The srk2d/e/i
      triple mutant lacking all three members of subclass III SnRK2 and the
      cipk26/3/9/23 quadruple mutant lacking CIPK26, CIPK3, CIPK9, and CIPK23 showed
      reduced shoot growth under high external Mg(2+) concentrations. Similarly,
      several ABA biosynthesis-deficient mutants, including aba2-1, were susceptible to
      high external Mg(2+) concentrations. Taken together, our findings provided
      genetic evidence that SRK2D/E/I and CIPK26/3/9/23 are required for plant growth
      under high external Mg(2+) concentrations in Arabidopsis. Furthermore, we showed
      that ABA, a key molecule in water deficit stress signaling, also serves as a
      signaling molecule in plant growth under high external Mg(2+) concentrations.
      These results suggested that SRK2D/E/I- and CIPK26/3/9/23-mediated
      phosphorylation signaling pathways maintain cellular Mg(2+) homeostasis. 

PMID- 25614065
TI  - Root system markup language: toward a unified root architecture description
      language.
AB  - The number of image analysis tools supporting the extraction of architectural
      features of root systems has increased in recent years. These tools offer a handy
      set of complementary facilities, yet it is widely accepted that none of these
      software tools is able to extract in an efficient way the growing array of static
      and dynamic features for different types of images and species. We describe the
      Root System Markup Language (RSML), which has been designed to overcome two major
      challenges: (1) to enable portability of root architecture data between different
      software tools in an easy and interoperable manner, allowing seamless
      collaborative work; and (2) to provide a standard format upon which to base
      central repositories that will soon arise following the expanding worldwide root
      phenotyping effort. RSML follows the XML standard to store two- or three
      dimensional image metadata, plant and root properties and geometries, continuous
      functions along individual root paths, and a suite of annotations at the image,
      plant, or root scale at one or several time points. Plant ontologies are used to
      describe botanical entities that are relevant at the scale of root system
      architecture. An XML schema describes the features and constraints of RSML, and
      open-source packages have been developed in several languages (R, Excel, Java,
      Python, and C#) to enable researchers to integrate RSML files into popular
      research workflow.

PMID- 25614066
TI  - Does morphological and anatomical plasticity during the vegetative stage make
      wheat more tolerant of water deficit stress than rice?
AB  - Water scarcity and the increasing severity of water deficit stress are major
      challenges to sustaining irrigated rice (Oryza sativa) production. Despite the
      technologies developed to reduce the water requirement, rice growth is seriously
      constrained under water deficit stress compared with other dryland cereals such
      as wheat (Triticum aestivum). We exposed rice cultivars with contrasting
      responses to water deficit stress and wheat cultivars well adapted to water
      limited conditions to the same moisture stress during vegetative growth to
      unravel the whole-plant (shoot and root morphology) and organ/tissue (root
      anatomy) responses. Wheat cultivars followed a water-conserving strategy by
      reducing specific leaf area and developing thicker roots and moderate tillering.
      In contrast, rice 'IR64' and 'Apo' adopted a rapid water acquisition strategy
      through thinner roots under water deficit stress. Root diameter, stele and xylem
      diameter, and xylem number were more responsive and varied with different
      positions along the nodal root under water deficit stress in wheat, whereas they
      were relatively conserved in rice cultivars. Increased metaxylem diameter and
      lower metaxylem number near the root tips and exactly the opposite phenomena at
      the root-shoot junction facilitated the efficient use of available soil moisture
      in wheat. Tolerant rice 'Nagina 22' had an advantage in root morphological and
      anatomical attributes over cultivars IR64 and Apo but lacked plasticity, unlike
      wheat cultivars exposed to water deficit stress. The key traits determining the
      adaptation of wheat to dryland conditions have been summarized and discussed. 

PMID- 25614067
TI  - Optimal microdomain crosstalk between endoplasmic reticulum and mitochondria for
      Ca2+ oscillations.
AB  - A Ca(2+) signaling model is proposed to consider the crosstalk of Ca(2+) ions
      between endoplasmic reticulum (ER) and mitochondria within microdomains around
      inositol 1, 4, 5-trisphosphate receptors (IP3R) and the mitochondrial Ca(2+)
      uniporter (MCU). Our model predicts that there is a critical IP3R-MCU distance at
      which 50% of the ER-released Ca(2+) is taken up by mitochondria and that
      mitochondria modulate Ca(2+) signals differently when outside of this critical
      distance. This study highlights the importance of the IP3R-MCU distance on Ca(2+)
      signaling dynamics. The model predicts that when MCU are too closely associated
      with IP3Rs, the enhanced mitochondrial Ca(2+) uptake will produce an increase of
      cytosolic Ca(2+) spike amplitude. Notably, the model demonstrates the existence
      of an optimal IP3R-MCU distance (30-85 nm) for effective Ca(2+) transfer and the
      successful generation of Ca(2+) signals in healthy cells. We suggest that the
      space between the inner and outer mitochondria membranes provides a defense
      mechanism against occurrences of high [Ca(2+)]Cyt. Our results also hint at a
      possible pathological mechanism in which abnormally high [Ca(2+)]Cyt arises when
      the IP3R-MCU distance is in excess of the optimal range. 

PMID- 25614069
TI  - The crop QTLome comes of age.
AB  - Recent progress in genomics and phenomics allows for a more accurate and
      comprehensive characterization of the Quantitative Trait Loci (QTLs)-hereafter
      defined 'QTLome' as a whole-that govern the variation targeted in breeding
      programs. High-density genotyping now provides unambiguous identification of QTL
      alleles, and for several traits beneficial alleles at major QTLs have already
      been deployed in marker-assisted breeding. However, the amount of QTLome
      information is enormous and approaches to distill and translate this information
      to breeders remain to be refined. Improved QTL meta-analyses, better estimation
      of QTL effects, improved crop modelling and full sharing of raw QTL data will
      enable a more effective exploitation of the QTLome.

PMID- 25614068
TI  - Definitive radiotherapy for primary vaginal cancer: correlation between treatment
      patterns and recurrence rate.
AB  - The purpose of this study was to determine the outcomes and optimal practice
      patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and
      2012, 49 patients were treated with definitive radiotherapy for primary vaginal
      cancer in three hospitals. Of these, 15 patients (31%) had clinically positive
      regional lymph node metastasis. A total of 34 patients (70%) received external
      beam radiotherapy with high-dose-rate brachytherapy (interstitial or
      intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated
      with local radiotherapy. The median follow-up was 33 months (range: 1-169
      months). The 3-year overall survival (OS), disease-free survival (DFS), and loco
      regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate
      analysis, the histological type (P = 0.044) was significant risk factors for LRC.
      In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients
      (38%) who did not undergo prophylactic lymph node irradiation had lymph node
      recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic
      pelvic irradiation. For Stage III-IV tumors, the local recurrence rate was 50%
      and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or
      clinical Stage N1 had a higher recurrence rate with treatment using a single
      modality compared with the recurrence rate using combined modalities. In
      conclusion, our treatment outcomes for vaginal cancer were acceptable, but
      external beam radiotherapy with brachytherapy (interstitial or intracavitary) was
      needed regardless of FIGO stage. Improvement of treatment outcomes in cases of
      FIGO Stage III or IV remains a significant challenge. 

PMID- 25614070
TI  - Plant GSTome: structure and functional role in xenome network and plant stress
      response.
AB  - Glutathione transferases (GSTs) represent a major group of detoxification
      enzymes. All plants possess multiple cytosolic GSTs, each of which displays
      distinct catalytic as well as non-catalytic binding properties. The progress made
      in recent years in the fields of genomics, proteomics and protein crystallography
      of GSTs, coupled with studies on their molecular evolution, diversity and
      substrate specificity has provided new insights into the function of these
      enzymes. In plants, GSTs appear to be implicated in an array of different
      functions, including detoxification of xenobiotics and endobiotics, primary and
      secondary metabolism, stress tolerance, and cell signalling. This review focuses
      on plant GSTome and attempts to give an overview of its catalytic and functional
      role in xenome and plant stress regulatory networks. 

PMID- 25614071
TI  - Screening of antimicrobial activity of macroalgae extracts from the Moroccan
      Atlantic coast.
AB  - The aim of this work is the screening of the antimicrobial activity of seaweed
      extracts against pathogenic bacteria and yeasts. The antimicrobial activity of
      the dichloromethane and ethanol extracts of ten marine macroalgae collected from
      the Moroccan's Atlantic coast (El-Jadida) was tested against two Gram+ (Bacillus
      subtilis and Staphylococcus aureus) and two Gram- (Escherichia coli and
      Pseudomonas aeruginosa) human pathogenic bacteria, and against two pathogenic
      yeasts (Candida albicans and Cryptococcus neoformans) using the agar disk
      diffusion method. Seven algae (70%) of ten seaweeds are active against at least
      one pathogenic microorganisms studied. Five (50%) are active against the two
      studied yeast with an inhibition diameter greater than 15 mm for Cystoseira
      brachycarpa. Six (60%) seaweeds are active against at least one studied bacteria
      with five (50%) algae exhibiting antibacterial inhibition diameter greater than
      15 mm. Cystoseira brachycarpa, Cystoseira compressa, Fucus vesiculosus, and
      Gelidium sesquipedale have a better antimicrobial activity with a broad spectrum
      antimicrobial and are a potential source of antimicrobial compounds and can be
      subject of isolation of the natural antimicrobials.

PMID- 25614072
TI  - Spinocerebellar ataxia type 7: a neurodegenerative disorder with peripheral
      neuropathy.
AB  - BACKGROUND: Autosomal dominant spinocerebellar ataxias (SCA) are a group of
      inherited neurodegenerative disorders that typically show peripheral neuropathy.
      SCA7 is one of the rarest forms of SCA (<1/100,000 individuals). However, the
      disease shows a prevalence of ~800/100,000 inhabitants in certain regions of
      Mexico. This low global prevalence may explain, at least in part, the isolated
      anecdotal and limited clinical data regarding peripheral neuropathy in SCA7
      patients. AIM: To assess sensory and motor peripheral nerve action potentials in
      an SCA7 patients group and in healthy volunteers, and subsequently correlate the
      electrophysiological findings with clinical and genetic features. MATERIALS AND
      METHODS: We enrolled in our study, 13 symptomatic SCA7 patients with a confirmed
      molecular and clinical diagnosis, and 19 healthy volunteers as the control group.
      Nerve conduction studies were carried out using standard electromyography
      recording methods. The sensory and motor latency, amplitude and conduction
      velocity were recorded in both experimental groups and analyzed using the
      Student's t-test. RESULTS: SCA7 patients showed a significant prolongation of
      sensory nerve conduction latencies, as well as a decrease in sensory amplitudes.
      Decreases in motor amplitudes and peroneal conduction velocity were also
      observed. Finally, we found an association between CAG repeats and the severity
      of cerebellar and non-cerebellar symptoms with electrophysiological signs of
      demyelinization. DISCUSSION: Our results reveal the existence of a critical
      sensorimotor peripheral neuropathy in SCA7 patients. Moreover, we show that using
      sensitive electrophysiological tools to evaluate nerve conduction can improve the
      diagnosis and design of therapeutic options based on pharmacological and
      rehabilitative strategies. CONCLUSION: These findings demonstrate that SCA7 is a
      disease that globally affects the peripheral nervous system.

PMID- 25614073
TI  - pH influence on antibacterial efficacy of common antiseptic substances.
AB  - BACKGROUND: Wound infection plays an important role in compromised wound healing.
      A high bioburden impairs healing and leads to formation of a chronic wound.
      Distinctly higher pH values were observed in chronic wounds compared to acute
      wounds. However, there is only limited knowledge of pH dependency on the
      antibacterial efficacy of common antimicrobial substances. METHODS: This study
      investigated the pH influence on the antimicrobial efficacy of povidone (PVP)
      iodine, silver nitrate, chlorhexidine, octenidine and polihexanide against
      Staphylococcus aureus and Pseudomonas aeruginosa using the agar diffusion test
      and microplate laser nephelometry. RESULTS: The bactericidal activity of
      chlorhexidine and octenidine was mainly pH-independent in a pH range of 5.0-9.0.
      In contrast, polihexanide showed a significant efficacy increase at a higher pH.
      It was also found that the influence of the pH on antiseptics differs among
      species of bacteria. For instance, S. aureus exhibited an increasing sensitivity
      against silver nitrate with rising pH whereas the effect on P. aeruginosa was
      found to be distinctly decreased. The antimicrobial effect of PVP-iodine was
      strongly diminished with rising pH. CONCLUSIONS: The shift towards higher pH
      values in chronic wounds compared to acute wounds makes it imperative to know
      whether the antimicrobial efficacy of applied antimicrobial substances is altered
      by different pH levels. The results suggest that application of polihexanide
      might be advantageous for the management of wound infections, as both S. aureus
      and P. aeruginosa exhibited an increased susceptibility with rising pH.

PMID- 25614074
TI  - [Urodynamic testing before stress-incontinence surgery in women: cost
      effectiveness analysis and ethical considerations].

PMID- 25614075
TI  - [Long term biochemical recurrence free survival after radical prostatectomy for
      cancer: comparative analysis according to surgical approach and
      clinicopathological stage].
AB  - OBJECTIVE: To assess long term biochemical recurrence free survival after radical
      prostatectomy according to open, laparoscopic and robot-assisted surgical
      approach and clinicopathological stage. MATERIAL AND METHODS: A cohort study of
      1313 consecutive patients treated by radical prostatectomy for localized or
      locally advanced prostate cancer between 2000 and 2013. Open surgery (63.7%),
      laparoscopy (10%) and robot-assisted laparoscopy (26.4%) were performed.
      Biochemical recurrence was defined by PSA>0,1ng/mL. The biochemical recurrence
      free survival was described by Kaplan Meier method and prognostic factors were
      analysed by multivariable Cox regression. RESULTS: Median follow-up was 57 months
      (IQR: 31-90). Ten years biochemical recurrence free survival was 88.5%, 71.6% and
      53.5% respectively for low, intermediate and high-risk D'Amico groups. On
      multivariable analysis, the worse prognostic factor was Gleason score (P<0.001).
      Positive surgical margins rate was 53% in pT3 tumours and 24% in pT2 tumours
      (P<0.001). Biochemical recurrence free survival (P=0.06) and positive surgical
      margins rate (P=0.87) were not statistically different between the three surgical
      approaches. CONCLUSION: Biochemical recurrence free survival in our study does
      not differ according to surgical approach and is similar to published series. Ten
      years biochemical recurrence free survival for high-risk tumours without hormone
      therapy is 54% justifying the role of surgery in the therapeutic conversations in
      this group of tumours. LEVEL OF EVIDENCE: 3.

PMID- 25614076
TI  - [Post-surgical septic arthritis of the pubic symphysis].
AB  - The post-surgical septic arthritis of the pubic symphysis is a rare infection,
      often unrecognized because sometimes it is difficult to diagnose. It should be
      suspected in the presence of pelvic pain with fever and sometimes lameness or
      painful radiation to the lower limbs but the symptoms can be misleading. We
      report 3 cases of post surgical septic arthritis of the pubic symphysis to
      illustrate it. Differential diagnoses are numerous and additional tests not
      always specific. Computed tomography (CT) and magnetic resonance imaging (MRI)
      examinations are essential to substantiate the diagnosis or to guide sampling.
      The appropriate antibiotic treatment against the identified germ, which is
      extended at least six weeks, will most often, when started early, allow the
      healing though pain can persist for several months. 

PMID- 25614077
TI  - Prenatal diagnosis of open spina bifida in Emilia-Romagna.
AB  - OBJECTIVE: To report recent data on the epidemiology of pregnancies affected by
      open spina bifida in the Emilia-Romagna region of Italy. METHODS: All cases of
      open spina bifida diagnosed in the Emilia-Romagna region between 2001 and 2011
      and reported to the IMER regional registry were included in the study group. The
      pregnancy outcome was retrospectively assessed. RESULTS: In the study period out
      of 390,978 babies born in Emilia-Romagna 126 cases of open spina bifida were
      reported to the IMER registry, resulting in a global prevalence of 3.2 per 10,000
      births. Prenatal diagnosis was achieved in the vast majority of these cases
      (105/126; 83.3%) and in a great proportion of those women (85/105; 80.9%) who
      opted for termination of pregnancy. CONCLUSIONS: In a wide region of northern
      Italy where ultrasound anomaly scan is routinely offered to the general
      population, the vast majority of cases of open spina bifida are diagnosed
      antenatally and terminated electively.

PMID- 25614079
TI  - Estimated effects of white rice consumption and rice variety selection on
      incidence of type 2 diabetes in Cambodia.
AB  - OBJECTIVE: Rice consumption patterns are considered an important risk factor for
      diabetes in many countries. The present study aimed to model the impact of a
      shift in consumption of white rice from current to appropriately reduced levels
      and a shift in rice variety from one with a high glycaemic index to one with a
      low glycaemic index, on the burden of type 2 diabetes in Cambodia. DESIGN:
      Prevent Plus software was used to model the impact of selected changes to white
      rice consumption on the burden of type 2 diabetes. Data used for modelling
      included: demographic projections, relative risk estimates for white rice
      consumption and diabetes, diabetes incidence, rice type and quantities consumed.
      The 10-year projections were based on different scenarios of changes in risk
      factors. RESULTS: With no intervention, 10-year projections showed that total new
      diabetes cases will increase from 11 315 (9.1 per 10 000 person-years) for the
      year 2011 to 14 852 new cases (12.4 per 10 000 person-years) in 2020. However,
      this increase will be reduced by 27 % (average across 10 years) with a change in
      rice variety from Phka Rumdual to IR66 and by 26 % (average across 10 years) with
      a 25 % reduction in quantity from current consumption levels. CONCLUSIONS:
      Changing rice consumption patterns has potential for an important impact on
      diabetes risk, with a change of rice variety having a similar impact on the
      burden of diabetes in communities consuming rice with a high glycaemic index as a
      25 % reduction in the quantity of rice consumed. Similar effects are likely for
      other countries with rice as a staple food, diversity in rice varieties and high
      incidence of diabetes.

PMID- 25614080
TI  - Effect on left ventricular mass and geometry in patients with takotsubo
      cardiomyopathy.
AB  - OBJECTIVES: Takotsubo cardiomyopathy (TTC) is a condition of transient left
      ventricular (LV) dysfunction. The effects on LV mass (LVM) and geometry have not
      been studied enough in TTC. Retrospectively, we analyzed our TTC cohort both by
      transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI), for
      comparative purposes. DESIGN: Thirteen women undergoing TTE and MRI, at onset and
      three months later, were included. LVM was estimated by MRI, and two TTE methods.
      Segmental wall thickness (SWT) was measured, while radial strain was assessed by
      TTE. Data analysis included Wilcoxon's test (between phases), Mann-Whitney U test
      and McNemar's test (between and within groups). Bland-Altman analyses were used
      for intertechnique coherence, while interactions regarding TTE were tested using
      Spearman's coefficient. RESULTS: LVM decreased during recovery (p < 0.05), by MRI
      and one of the TTE methods; truncated ellipsoid formula (TEF), which also showed
      relatively better coherence compared with MRI. SWT decreased in two of three
      sites, by both modalities, but with ambiguous coherence there between. The TEF
      data interacted partially with a demonstrated increase in radial strain.
      CONCLUSIONS: TTC associates with acute increase in LVM, which appears to be an
      apical effect, tending to follow the changes in concentric wall motion. MRI and
      TTE show adequate coherence; primarily for the TEF method regarding LVM.

PMID- 25614078
TI  - MpSaci is a widespread gypsy-Ty3 retrotransposon highly represented by non
      autonomous copies in the Moniliophthora perniciosa genome.
AB  - Transposons are an important source of genetic variation. The phytopathogen
      Moniliophthora perniciosa shows high level of variability but little is known
      about the role of class I elements in shaping its genome. In this work, we aimed
      the characterization of a new gypsy/Ty3 retrotransposon species, named MpSaci, in
      the M. perniciosa genome. These elements are largely variable in size, ranging
      from 4 to 15 kb, and harbor direct long terminal repeats (LTRs) with varying
      degrees of similarity. Approximately, all of the copies are non-autonomous as
      shifts in the reading frame and stop codons were detected. Only two elements
      (MpSaci6 and MpSaci9) code for GAG and POL proteins that possess functional
      domains. Conserved domains that are typically not found in retrotransposons were
      detected and could potentially impact the expression of neighbor genes. Solo LTRs
      and several LARDs (large retrotransposon derivative) were detected. Unusual
      elements containing small sequences with or without interruptions that are
      similar to gag or different pol domains and presenting LTRs with different levels
      of similarities were identified. Methylation was observed in MpSaci reverse
      transcriptase sequences. Distribution analysis indicates that MpSaci elements are
      present in high copy number in the genomes of C-, S- and L-biotypes of M.
      perniciosa. In addition, C-biotype isolates originating from the state of Bahia
      have fragments in common with isolates from the Amazon region and two
      hybridization profiles related to two chromosomal groups. RT-PCR analysis reveals
      that the gag gene is constitutively expressed and that the expression is
      increased at least three-fold with nutrient depravation even though no new
      insertion were observed. These findings point out that MpSaci collaborated and,
      even though is primarily represented by non-autonomous elements, still might
      contribute to the generation of genetic variability in the most important cacao
      pathogen in Brazil. 

PMID- 25614081
TI  - An analysis of product wastage arising from dosing increment granularity in four
      modern growth hormone administration devices.
AB  - OBJECTIVE: Human growth hormone (hGH) delivery systems differ in the size of the
      dose increments that can be set by the patient, affecting proximity to the target
      (i.e., prescribed) dose which can be attained. We investigated differences in
      dosing increment granularity in NordiFlex(r), FlexPro(r), NordiPen(r) (all
      multiple dose devices) and MiniQuick(r) (single dose) delivery systems. METHODS:
      A simulation model was developed to project hGH dosing in pediatric patients with
      growth hormone deficiency, small for gestational age or Turner syndrome,
      calculating the nearest dose above the target dose administrable by each device
      in typical EU and US cohorts and projecting the excess dose (hGH wastage) over 1
      year of typical use. RESULTS: The device with the smallest dosing increment
      (FlexPro 5 mg; 0.025 mg dosing increment) was projected to administer doses < 1%
      above the target across all indications. MiniQuick (0.2 mg dosing increment) was
      projected to deliver between 5 and 6% above the target dose. None of the
      sensitivity analyses changed the conclusion that larger dosing increments result
      in more hGH wastage. CONCLUSIONS: In addition to increasing dosing accuracy,
      finer dosing increments may result in reductions in unnecessary hGH usage, which
      may in turn result in reductions in the cost of hGH treatment borne by the health
      care payer.

PMID- 25614083
TI  - "It Was the Best Decision of My Life": a thematic content analysis of former
      medical tourists' patient testimonials.
AB  - BACKGROUND: Medical tourism is international travel with the intention of
      receiving medical care. Medical tourists travel for many reasons, including cost
      savings, limited domestic access to specific treatments, and interest in
      accessing unproven interventions. Medical tourism poses new health and safety
      risks to patients, including dangers associated with travel following surgery,
      difficulty assessing the quality of care abroad, and complications in continuity
      of care. Online resources are important to the decision-making of potential
      medical tourists and the websites of medical tourism facilitation companies
      (companies that may or may not be affiliated with a clinic abroad and help
      patients plan their travel) are an important source of online information for
      these individuals. These websites fail to address the risks associated with
      medical tourism, which can undermine the informed decision-making of potential
      medical tourists. Less is known about patient testimonials on these websites,
      which can be a particularly powerful influence on decision-making. METHODS: A
      thematic content analysis was conducted of patient testimonials hosted on the
      YouTube channels of four medical tourism facilitation companies. Five videos per
      company were viewed. The content of these videos was analyzed and themes
      identified and counted for each video. RESULTS: Ten main themes were identified.
      These themes were then grouped into three main categories: facilitator
      characteristics (e.g., mentions of the facilitator by name, reference to the
      price of the treatment or to cost savings); service characteristics (e.g., the
      quality and availability of the surgeon, the quality and friendliness of the
      support staff); and referrals (e.g., referrals to other potential medical
      tourists). These testimonials were found either not to mention risks associated
      with medical tourism or to claim that these risks can be effectively managed
      through the use of the facilitation company. The failure fully to address the
      risks of medical tourism can undermine the informed decision-making of potential
      medical tourists, particularly given the considerable influence on decision
      making by patient testimonials. CONCLUSIONS: Regulation of these global companies
      is difficult, making the development of testimonials highlighting the risks of
      medical tourism essential. Additional research is needed on the impact of patient
      testimonial videos on the decision-making of potential medical tourists.

PMID- 25614084
TI  - Fungemia caused by Yarrowia lipolytica.
AB  - Yarrowia lipolytica is weakly pathogenic yeast, which is rarely isolated from the
      blood. We report unusual cases of Y. lipolytica fungemia occurred between October
      2012 and June 2014 in the intensive care unit (ICU) of the UH Habib Bourguiba
      Sfax. During this period, 55 cases of Y. lipolytica septicemia were diagnosed.
      There were 44 men and 11 women (sex ratio = 4).The median age was 43 years. The
      broad-spectrum antibiotics (100 %), the catheterization (96 %), and the prolonged
      hospitalization in ICU (91 %) were the main risk factors. Patients were
      hospitalized in ICU, mostly, for polytraumatism (45.4 %), pneumopathy (9 %), and
      post-operative complications (7 %). Fever unresponsive to broad-spectrum
      antibacterial therapy was the predominant sign of infection (83.6 %). Y.
      lipolytica was isolated in one or several blood cultures (14.5 %) and in the
      catheter tip culture of nine patients (16.3 %).Treatment was based on intravenous
      amphotericin B (58.2 %), fluconazole (45.4 %) and/or removal catheter (69 %).
      Apyrexia or blood cultures sterilization was obtained for 34 patients (61.8 %).
      Y. lipolytica candidemia is an opportunistic and emerging human yeast pathogen.
      It can reach to the bloodstream of immunocompromised or critically ill patients
      during hospitalization through intravascular catheterization. Further clinical
      data need to be evaluated for formulating management strategies of seriously ill
      patients infected with uncommon fungal agents.

PMID- 25614082
TI  - Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell
      vaccination combined with gemcitabine in pancreatic cancer.
AB  - This study aimed to evaluate the feasibility of and immune response to Wilms
      tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with
      gemcitabine (DCGEM) as a first-line therapy among patients with advanced
      pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed
      DC vaccination (1 * 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2) )
      on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated
      using the delayed-type hypersensitivity (DTH) skin test, interferon-gamma enzyme
      linked immunospot and HLA tetramer assays, along with assays for various
      immunological factors. DCGEM was well-tolerated, and the relative dose intensity
      of gemcitabine was 87%. Disease control associated with a low
      neutrophil/lymphocyte ratio was observed in all three patients with DTH
      positivity; it was also correlated with a low percentage of granulocytic myeloid
      derived suppressor cells in the pretreatment peripheral blood (P = 0.017).
      Patients with liver metastases and high levels of inflammatory markers such as C
      reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1
      specific immune response was induced in them. WT1 peptide-pulsed DCGEM is
      feasible and effective for inducing anti-tumor T-cell responses. Our results
      support future investigations for pancreatic cancer patients with non-liver
      metastases and favorable immunological conditions. This trial was registered with
      the University hospital Medical Information Network (UMIN) Clinical Trials
      Registry (http://www.umin.ac.jp/ctr/ number: UMIN-000004855). 

PMID- 25614085
TI  - Detection and quantification of fluconazole within Candida glabrata biofilms.
AB  - Candida infections are often associated with biofilms and consequent high
      resistance to most common drugs (e.g. azoles). These resistance mechanisms are
      not only associated with the biofilm yeast physiology, but also with the presence
      of a diffusional barrier imposed by the biofilm matrix; however, the real
      biochemical role of the biofilm components remains very unclear. So, in order to
      further clarify this issue, we intend to determine, for the first time,
      fluconazole in biofilms within both supernatants and matrices. Candida biofilms
      were formed in the presence of fluconazole, and it was recovered from both
      supernatant and matrix cell-free fractions. Then, high-pressure liquid
      chromatography was used to identify and quantify the amount of drug that was
      present in the two fractions. Moreover, this study also showed that the presence
      of fluconazole in both fractions indicated that the drug administrated did not
      completely reach the cells, so this phenomena can easily be associated with lower
      biofilm susceptibility, since the drug administered did not completely reach the
      cells.

PMID- 25614086
TI  - Transcription factor TIP27 regulates glucose homeostasis and insulin sensitivity
      in a PI3-kinase/Akt-dependent manner in mice.
AB  - BACKGROUND/OBJECTIVES: Juxtaposed with another zinc-finger gene 1 (TIP27 or
      JAZF1) is a 27-kDa transcription factor, and genome-wide association studies have
      recently revealed TIP27 to be associated with type 2 diabetes. However, little is
      known about its role in the regulation of metabolism. In this study, we
      investigated the effects of TIP27 overexpression on glucose homeostasis and
      insulin signaling in high-fat diet (HFD)-fed TIP27 transgenic (TIP27-Tg) mice and
      db/db mice. METHODS: We assessed the effects of TIP27 overexpression in both
      TIP27-Tg mice and db/db mice on glucose metabolism and changes in insulin
      sensitivity during glucose (GTT) and insulin (ITT) tolerance tests. A
      hyperinsulinemic-euglycemic clamp was performed on TIP27-Tg mice. Real-time
      quantitative PCR and western blotting were used to assess mRNA and protein
      expressions. RESULTS: TIP27 overexpression in TIP27-Tg mice and in db/db mice led
      to reduced total cholesterol and fasting plasma insulin levels, and enhanced
      glucose tolerance and insulin sensitivity during GTT and ITT. Hyperinsulinemic
      euglycemic clamp experiments demonstrated that HFD-fed TIP27-Tg mice had lower
      hepatic glucose production and higher insulin sensitivity compared with
      nontransgenic littermates. In addition, the hepatic expressions of
      phosphoenolpyruate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) mRNAs
      and proteins were significantly decreased, whereas the phosphorylation of insulin
      receptor, insulin receptor substrate-1, adenosine monophosphate-activated protein
      kinase and Akt kinase (Akt) in the liver was significantly increased in HFD-fed
      TIP27-Tg mice compared with nontransgenic littermates. Adenovirus-mediated TIP27
      overexpression in db/db mice also decreased the expression of gluconeogenic genes
      and increased the phosphorylation of insulin signaling molecules in the liver
      compared with controls. Finally, LY294002, a phosphatidylinositol 3-kinase (PI3
      kinase) inhibitor, abolished the suppressive effect of TIP27 overexpression on
      PEPCK and G6Pase expression. CONCLUSIONS: TIP27 has an important role in glucose
      homeostasis through the regulation of hepatic glucose metabolism and insulin
      sensitivity. Furthermore, this regulation requires activation of PI3-kinase.

PMID- 25614087
TI  - The impact of maternal obesity on iron status, placental transferrin receptor
      expression and hepcidin expression in human pregnancy.
AB  - BACKGROUND: Obesity is associated with decreased iron status, possibly due to a
      rise in hepcidin, an inflammatory protein known to reduce iron absorption. In
      animals, we have shown that maternal iron deficiency is minimised in the foetus
      by increased expression of placental transferrin receptor (pTFR1), resulting in
      increased iron transfer at the expense of maternal iron stores. OBJECTIVE: This
      study examines the effect of obesity during pregnancy on maternal and neonatal
      iron status in human cohorts and whether the placenta can compensate for
      decreased maternal iron stores by increasing pTFR1 expression. SUBJECTS/METHODS:
      A total of 240 women were included in this study. One hundred and fifty-eight
      placentas (Normal: 90; Overweight: 37; Obese: 31) were collected at delivery.
      Maternal iron status was measured by determining serum transferrin receptor
      (sTFR) and ferritin levels at 24 and 34 weeks and at delivery. Hepcidin in
      maternal and cord blood was measured by ELISA and pTFR1 in placentas by western
      blotting and real-time RT-PCR. RESULTS: Low iron stores were more common in obese
      women. Hepcidin levels (ng ml(-1)) at the end of the pregnancy were higher in
      obese than normal women (26.03+/-12.95 vs 18.00+/-10.77, P<0.05). Maternal
      hepcidin levels were correlated with maternal iron status (sTFR r=0.2 P=0.025),
      but not with neonatal values. mRNA and protein levels of pTFR1 were both
      inversely related to maternal iron status. For mRNA and all women, sTFR r=0.2
      P=0.044. Ferritin mRNA levels correlated only in overweight women r=-0.5 P=0.039
      with hepcidin (r=0.1 P=0.349), irrespective of maternal body mass index (BMI).
      CONCLUSIONS: The data support the hypothesis that obese pregnant women have a
      greater risk of iron deficiency and that hepcidin may be a regulatory factor.
      Further, we show that the placenta responds to decreased maternal iron status by
      increasing pTFR1 expression.

PMID- 25614088
TI  - Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid
      deposition in early infancy.
AB  - Sexual dimorphism in adiposity is well described in adults, but the age at which
      differences first manifest is uncertain. Using a prospective cohort, we describe
      longitudinal changes in directly measured adiposity and intrahepatocellular lipid
      (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63
      days, infants underwent quantification of adipose tissue depots by whole-body
      magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic
      resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys
      and 30 girls). In the neonatal period girls are more adipose in relation to body
      size than boys. At follow-up (median age 63 days), girls remained significantly
      more adipose. The greater relative adiposity that characterises girls is
      explained by more subcutaneous adipose tissue and this becomes increasingly
      apparent by follow-up. No significant sex differences were seen in IHCL. Sex
      specific differences in infant adipose tissue distribution are in keeping with
      those described in later life, and suggest that sexual dimorphism in adiposity is
      established in early infancy. 

PMID- 25614089
TI  - Ulnar drift in rheumatoid arthritis: a review of biomechanical etiology.
AB  - The objective of this article is to summarize current understanding of
      biomechanical factors that cause ulnar drift in the hands of patients with
      rheumatoid arthritis. This was done through literature review of published
      articles on the mechanical etiology of ulnar drift. There are several theories
      regarding the cause of ulnar drift, however conclusive evidence is still lacking.
      Current mechanical factors that are postulated to play a role include: failure of
      the collateral ligaments, intra-articular pressure changes, degenerative changes
      in the carpal and metacarpal anatomy, muscle hypoxia induced changes in wrist
      tension, and exacerbating activities of daily living. Although current theories
      regarding ulnar drift almost universally include an at least partially mechanical
      rationale, the causes may be multifactorial. Significantly more research is
      needed to elucidate the relative importance of mechanical factors leading to
      significant ulnar drift concurrent with advanced rheumatoid arthritis. 

PMID- 25614090
TI  - Cellular force signal integration through vector logic gates.
AB  - The multi-signal mechanical environment mammalian cells experience is often
      unaccounted for in current mechanical stimulation studies. To address this we
      developed a novel technique to induce dual integrated force inputs, uniaxial
      stretch and fluid shear stress and present here for the first time a vector logic
      gate framework to characterize cellular response as a function of cytoskeletal
      reorganization. Using this framework we found that under fluid shear stress and
      uniaxial stretch NIH 3T3 fibroblasts responded by the Stretch OR Shear vector
      logic-gate and HUVECs responded by the NOT Stretch OR Shear vector logic-gate. We
      further developed a parsimonious model of cellular response to multiple
      mechanical stimuli, which provides a unifying model that captured the
      experimental response of both cell types. 

PMID- 25614091
TI  - Measles and the risk posed by international travelers at the time of elimination
      or post-elimination.

PMID- 25614092
TI  - Tropheryma whipplei as a causative agent of travelers' diarrhea: further studies
      required. Reply to Razavi SM.

PMID- 25614093
TI  - Gender bias in training of medical students in obstetrics and gynaecology: a myth
      or reality?
AB  - OBJECTIVE: To investigate the experience of medical students during a clinical
      attachment in obstetrics and gynaecology (O&G). STUDY DESIGN: A questionnaire was
      distributed to medical students who completed their O&G posting between August
      2012 and August 2013. The first part included basic demographic details (age,
      gender, and ethnicity) and frequency of actual clinical experience; the second
      part explored students' perception of their training and their relationship with
      other staff, in particular feeling of discrimination by specified groups of
      medical personnel. The responses were recorded using a Likert scale and were
      recategorised during analysis. RESULTS: A total of 370 questionnaires were
      distributed, and 262 completed questionnaires were returned, giving a response
      rate of 71%. Female students had a significantly higher median (IqR) number of
      vaginal examinations performed 0.25(0.69) (p=0.002) compared to male students.
      Male students experienced a higher proportion of patient rejections during
      medical consultation, 87% vs. 32% of female students (p<0.001), a higher rate of
      refusal for clerking (71.4% vs. 57.5% of females, p=0.035) and a higher rate of
      patients declining consent for internal examination (93.3% vs. 67.6% of females,
      p<0.001). The majority of male students felt that their gender negatively
      affected their learning experience (87% vs. 27.4% of the female students,
      p<0.001). Male students reported a significantly higher proportion of
      discrimination against their gender by medical officers (p=0.018) and
      specialists/consultants (p<0.001) compared to females but there was no
      discrimination between genders by staff nurses or house officers. A majority
      (58%) of female students stated an interest in pursuing O&G as a future career
      compared to 31.2% of male students. CONCLUSIONS: Our study confirmed that gender
      bias exists in our clinical setting as male students gain significantly less
      experience than female students in pelvic examination skills. We also
      demonstrated that compared to female students, male students experience higher
      levels of discrimination against their gender by trainers who are medical
      officers and specialists/consultants. Trainers must improve their attitudes
      towards male students, to encourage them and make them feel welcome in the
      clinical area. We must minimize gender discrimination and educational inequities
      experienced by male students, in order to improve their learning experience.

PMID- 25614094
TI  - Dynamic state of water molecular displacement of the brain during the cardiac
      cycle in idiopathic normal pressure hydrocephalus.
AB  - The predictive accuracy of iNPH diagnoses could be increased using a combination
      of supplemental tests for iNPH. To evaluate the dynamic state of water
      displacement during the cardiac cycle in idiopathic normal pressure hydrocephalus
      (iNPH), we determined the change in water displacement using q-space analysis of
      diffusion magnetic resonance image. ECG-triggered single-shot diffusion echo
      planar imaging was used. Water displacement was obtained from the displacement
      probability profile calculated by Fourier transform of the signal decay fitted as
      a function of the reciprocal spatial vector q. Then maximum minus minimum
      displacement (delta-displacement), of all cardiac phase images was calculated. We
      assessed the delta-displacement in white matter in patients with iNPH and
      atrophic ventricular dilation (atrophic VD), and in healthy volunteers (control
      group). Delta-displacement in iNPH was significantly higher than those in the
      atrophic VD and control. This shows that water molecules of the white matter in
      iNPH are easily fluctuated by volume loading of the cranium during the cardiac
      cycle, due to the decrease in intracranial compliance. There was no significant
      correlation between delta-displacement and displacement. The delta-displacement
      and the displacement do not necessarily yield the same kind of information. Delta
      displacement demonstrated to obtain biophysical information about fluctuation.
      This analysis may be helpful in the understanding physiology and pathological
      condition in iNPH and the assisting in the diagnosis. 

PMID- 25614095
TI  - An automated approach to the segmentation of HEp-2 cells for the indirect
      immunofluorescence ANA test.
AB  - The automatization of the analysis of Indirect Immunofluorescence (IIF) images is
      of paramount importance for the diagnosis of autoimmune diseases. This paper
      proposes a solution to one of the most challenging steps of this process, the
      segmentation of HEp-2 cells, through an adaptive marker-controlled watershed
      approach. Our algorithm automatically conforms the marker selection pipeline to
      the peculiar characteristics of the input image, hence it is able to cope with
      different fluorescent intensities and staining patterns without any a priori
      knowledge. Furthermore, it shows a reduced sensitivity to over-segmentation
      errors and uneven illumination, that are typical issues of IIF imaging. 

PMID- 25614096
TI  - High-throughput RNA sequencing reveals the effects of 2,2',4,4' 
      tetrabromodiphenyl ether on retina and bone development of zebrafish larvae.
AB  - BACKGROUND: 2,2',4,4'-Tetrabromodiphenyl ether (BDE47) is a prevalent
      environmental pollutant and has been demonstrated to be a serious toxicant in
      both humans and animals, but little is known about the molecular mechanism
      underlying its toxic effect on the early development of vertebrates. BDE47
      treated zebrafish larvae were found to present the light-related locomotion
      reduction in our previous study, therefore, we aimed to use high throughput
      sequencing to investigate the possible reasons from a transcriptomic perspective.
      RESULTS: By exposing zebrafish embryos/larvae to 5 MUg/l and 500 MUg/l BDE47, we
      measured the influence of BDE47 on the mRNA expression profiles of zebrafish
      larvae until 6 days post-fertilization, using Illumina HiSeq 2000 sequencing.
      Differential expression analysis and gene enrichment analysis respectively
      revealed that a great number of genes, and gene sets based on two popular
      terminologies, were affected by the treatment of 500 MUg/l BDE47. Among them,
      BDE47 caused changes in the retinal metabolism and related biological processes
      involving eye morphogenesis and visual perception, as confirmed by disordered
      photoreceptor arrangement and thickened bipolar cell layer of larval retina from
      histological observations. Other altered genes such as pth1a and collaborative
      cathepsin family exhibited disrupted bone development, which was consistent with
      the body curvature phenotype. The transcriptome of larvae was not significantly
      affected by the treatment of 5 MUg/l BDE47, as well as the treatment of DMSO
      vehicle. CONCLUSIONS: Our results suggest that high BDE47 concentrations disrupt
      the eye and bone development of zebrafish larvae based on both transcriptomic and
      morphological evidences. The abnormal visual perception may result in the
      alteration of dark adaption, which was probably responsible for the abnormal
      larval locomotion. Body curvature arose from enhanced bone resorption because of
      the intensive up-regulation of related genes. We also proposed the larval retina
      as a novel potential target tissue for BDE47 exposure.

PMID- 25614097
TI  - Comparison between one-stent versus two-stent technique for treatment of left
      main bifurcation lesions: A large single-center data.
AB  - BACKGROUND: Comparisons between one- and two-stent strategies for unprotected
      left main (UPLM) coronary bifurcation disease have yielded inconsistent results.
      This large-sample, long-term follow-up study comparatively assessed stenting
      strategy impact in patients with distal left main disease. METHODS: Totally,
      1,528 consecutive patients underwent left main percutaneous coronary intervention
      in a single center from January 2004 to December 2010 were enrolled; among them,
      1033 patients with distal UPLM lesions treated by one (n = 661) or two (n = 372)
      drug-eluting stent (DES) technique were comparatively analyzed. Primary outcome
      was rate of major adverse cardiovascular events (MACE), defined as a composite of
      death, myocardial infarction (MI), and target vessel revascularization (TVR).
      RESULTS: Overall, baseline SYNTAX score was low-intermediate (one stent: 25 +/- 6
      vs. two stents: 26 +/- 5, P = 0.02), and mean clinical SYNTAX score was similar
      between groups (one stent: 30 +/- 22 vs. two stents: 31 +/- 22, P = 0.47). Final
      kissing balloon was successfully achieved in most of the patients treated with
      two-stent technique (one stent: 30.9% vs. two stents: 96.0%, P < 0.01), and use
      of intravascular ultrasound was also more common in them (one stent: 32.2% vs.
      two stents: 53.8%, P < 0.01). At mean 4 years follow-up, rates of MACE (one
      stent: 9.2% vs. two stents: 11.6%, P = 0.23), death, MI, and TVR were similar
      between groups. In multivariate propensity-matched regression analysis, two-stent
      technique was not predictive of MACE. CONCLUSIONS: For patients with distal UPLM
      disease and low-intermediate SYNTAX score treated with DES, clinical outcomes
      appear similar between optimal two-stent implantation and one-stent strategy. (c)
      2015 Wiley Periodicals, Inc.

PMID- 25614098
TI  - Triggering activity of catalytic rod-like supramolecular polymers.
AB  - Supramolecular polymers based on benzene-1,3,5-tricarboxamides (BTAs)
      functionalized with an L- or D-proline moiety display high catalytic activity
      towards aldol reactions in water. High turnover frequencies (TOF) of up to 27*10(
      4) s(-1) and excellent stereoselectivities (up to 96% de, up to 99% ee) were
      observed. In addition, the catalyst could be reused and remained active at
      catalyst loadings and substrate concentrations as low as 0.1 mol % and 50 mM,
      respectively. A temperature-induced conformational change in the supramolecular
      polymer triggers the high activity of the catalyst. The supramolecular polymer's
      helical sense in combination with the configuration of the proline (L- or D-) is
      responsible for the observed selectivity.

PMID- 25614099
TI  - Pseudomonas aeruginosa activates the quorum sensing LuxR response regulator
      through secretion of 2-aminoacetophenone.
AB  - In this study we identify a volatile compound produced by Pseudomonas aeruginosa,
      which can specifically activate the LuxR quorum-sensing response regulator of
      Vibrio fischeri. Comparative gas-chromatography analysis between P. aeruginosa
      wild type and a DeltalasR mutant strain implied that the active volatile is 2
      aminoacetophenone. The use of synthetic 2-aminoacetophenone and in silico docking
      analyses verified the activity of the molecule and provided putative interacting
      residues within the binding site. 

PMID- 25614100
TI  - Resolution of the cellular proteome of the nucleocapsid protein from a highly
      pathogenic isolate of porcine reproductive and respiratory syndrome virus
      identifies PARP-1 as a cellular target whose interaction is critical for virus
      biology.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to
      the swine industry and food security worldwide. The nucleocapsid (N) protein is a
      major structural protein of PRRSV. The primary function of this protein is to
      encapsidate the viral RNA genome, and it is also thought to participate in the
      modulation of host cell biology and recruitment of cellular factors to facilitate
      virus infection. In order to the better understand these latter roles the
      cellular interactome of PRRSV N protein was defined using label free quantitative
      proteomics. This identified several cellular factors that could interact with the
      N protein including poly [ADP-ribose] polymerase 1 (PARP-1), a cellular protein,
      which can add adenosine diphosphate ribose to a protein. Use of the PARP-1 small
      molecule inhibitor, 3-AB, in PRRSV infected cells demonstrated that PARP-1 was
      required and acted as an enhancer factor for virus biology. Serial growth of
      PRRSV in different concentrations of 3-AB did not yield viruses that were able to
      grow with wild type kinetics, suggesting that by targeting a cellular protein
      crucial for virus biology, resistant phenotypes did not emerge. This study
      provides further evidence that cellular proteins, which are critical for virus
      biology, can also be targeted to ablate virus growth and provide a high barrier
      for the emergence of drug resistance. 

PMID- 25614102
TI  - A lot of questions (and a few answers ...) in retroperitoneal fibrosis.

PMID- 25614101
TI  - Resistance of Klebsiella pneumoniae to the innate immune system of African green
      monkeys.
AB  - In recent years, an emergent Klebsiella pneumoniae hypermucoviscosity (HMV)
      phenotype has been associated with increased invasiveness and pathogenicity in
      primates. In this project, bacteria recovered from infected African green monkeys
      (AGM) (Chlorocebus aethiops sabaeus) were screened for HMV phenotype, and were
      compared to non-HMV isolates in in vitro, serum, and oxidative-mediated killing
      assays. Complement-mediated killing was assessed utilizing freshly collected
      serum from healthy AGM. Oxidative-mediated killing was investigated utilizing
      sodium hypochlorite and hydrogen peroxide. Compared to non-HMV isolates, HMV
      isolates were more resistant to serum-mediated and oxidative killing (p<0.05).
      Phagocytosis resistance was evaluated using AGM peripheral blood monocytes
      (PBMC), and results indicated that non-HMV isolates associated with the AGM PBMC
      to a greater extent than HMV isolates (p<0.001). Measurement of lactate
      dehydrogenase release showed that HMV isolates were more cytotoxic to AGM PBMC
      than non-HMV isolates (p<0.001). Thus, the hypermucoid phenotype appears to be an
      important virulence factor that promotes evasion of innate immune defenses. 

PMID- 25614103
TI  - Blind and constructive patriotism, national symbols and outgroup attitudes.
AB  - We examined whether there is a relationship between the different forms
      patriotism can take (i.e., blind vs. constructive) and different representations
      of one's own nation. We considered two types of national symbols representing the
      nation in terms of confrontation between groups (polarized symbols) and as a
      unique entity (unpolarized symbols). In Study 1 we found that blind patriotism
      was positively associated with the degree to which individuals perceived their
      nation through confrontation whereas constructive patriotism was positively
      associated with the degree to which individuals perceived their nation as unique
      entity. In Study 2 we tested how the relationship between blind patriotism and
      outgroup attitudes changed when the nation was defined either through
      confrontation or as a unique entity. The results emphasize the essential role of
      the specific meaning associated to the nation when studying patriotism and its
      relation to outgroup attitudes. 

PMID- 25614104
TI  - Herb-drug interaction between an anti-HIV Chinese herbal SH formula and
      atazanavir in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: With the prevalent use of highly active
      antiretroviral therapy (HAART) for AIDS patients since 1996, the mortality of
      HIV/AIDS patients has been remarkably decreased. With long-term use of HAART,
      drug resistance and side effects of antiretrovirals have been frequently
      reported, which not only reduce the efficacy, but also decreases the tolerance of
      patients. Traditional herbal medicine has become more popular among HIV/AIDS
      patients as adjuvant therapy to reduce these adverse effects of HAART. SH formula
      is a Chinese herbal formula consisting of five traditional Chinese herbs
      including Morus alba L., Glycyrrhiza glabra L., Artemisia capillaris Thumb.,
      Astragalus membranaceus Bge., and Carthamus tinctorius L. SH formula is
      clinically used for HIV treatment in Thailand. However, the possible
      pharmacokinetic interactions between these Chinese herbs and antiretroviral drugs
      have not been well documented. The aim of this study was to investigate the
      potential herb-drug interaction between SH herbal Chinese formula and the
      antiretroviral drug atazanavir (ATV). MATERIALS AND METHODS: The combination
      effect of SH formula and ATV on HIV protease was studied in HIV-1 protease
      inhibition assay in vitro. The inhibition of SH formula on rat CYP3A2 was
      assessed by detecting the formation of 1'-OH midazolam from midazolam in rat
      liver microsomes in vitro. The in vivo pharmacokinetic interaction between SH
      formula and ATV was investigated by measuring time-dependent plasma
      concentrations of ATV in male Sprague-Dawley rats with liquid chromatography-mass
      spectrometry. RESULTS: Through the in vitro HIV-1 protease inhibition assay,
      combination of SH formula (41.7-166.7 MUg/ml) and ATV (16.7-33.3 ng/ml) showed
      additive inhibition on HIV-1 protease activity than SH formula or ATV used alone.
      In vitro incubation assay indicated that SH formula showed a weak inhibition
      (IC50=231.2 ug/ml; Ki=98.2 ug/ml) on CYP3A2 activity in rat liver microsomes. In
      vivo pharmacokinetic study demonstrated that SH formula did not affect the
      metabolism of ATV in rats. CONCLUSIONS: Our study demonstrated for the first time
      that there is no metabolism-based herb-drug interaction between SH formula and
      ATV in rats, but this combination enhances the inhibition potentials against HIV
      protease activity. This observation may support the combinational use of anti-HIV
      treatment in human.

PMID- 25614105
TI  - An ethnobotanical study on medicinal plants in Espiye and its surrounding
      (Giresun-Turkey).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper provides significant ethnobotanical
      information on medicinal plants in Espiye in the Black Sea Region. Recording such
      data calls for urgency. This is the first ethnobotanical study in which
      statistical calculations about plants are carried out by means of FIC method in
      Northern (Espiye-Giresun) part of Turkey. This study aims to identify the wild
      plants collected for medicinal purposes by locals of Espiye which is located in
      the Black Sea Region of Turkey, and to identify the uses and local names of these
      wild plants. MATERIALS AND METHODS: A field study had been carried out for a
      period of approximately 2 years (2012-2014). During this period, information
      about medicinal use of 55 wild and 15 cultivated plants were collected.
      Demographic characteristics of participants, names of the local plants, their
      utilized parts and preparation methods were investigated and recorded. Through
      face-to-face interviews, we identified and recorded demographic characteristics
      of the respondents. We interviewed 128 persons who are over the age of 29. The
      plant taxa were collected within the scope of the study; and herbarium materials
      were prepared. In addition, the relative significance value of the taxa was
      determined, and informant consensus factor (FIC) was calculated for the medicinal
      plants included in the study. RESULTS: We have found out in the literature review
      of the plants included in our study that 70 plant taxa are already used for
      medicinal purposes while 3 plants are not available among the records in the
      literature. The most common families are Asteraceae, Rosaceae, Lamiaceae,
      Malvaceae, and Ericaceae. We include in our study and report for the first time
      the medicinal uses of Alchemilla crinita Buser, Stachys sylvatica L., and Thymus
      leucotrichus Hal. var. leucotrichus Hal. Names of local plants in Turkey vary
      especially due to vernaculars. The plants that the locals of Espiye use are
      called with the same or different local names in various parts of Anatolia.
      CONCLUSION: We found out that locals living in the research area use for
      therapeutic purpose 70 plants taxa which belong to 36 families. Turkish citizens
      with different ethnic backgrounds took the questionnaire. These people use these
      wild plants in treatment of several diseases. Comparison of the data obtained in
      this study with the experimental data obtained in the previous laboratory studies
      on the wild plants which grow in Espiye proved ethnobotanical usages to a great
      extent. Literature review indicated that the therapeutic plants that grow in
      Espiye are used in different parts of the world for the treatment of similar
      diseases.

PMID- 25614106
TI  - The molecular insight into the antihyperuricemic and renoprotective effect of
      Shuang Qi gout capsule in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Shuang-Qi gout capsule, a traditional Chinese
      medicine prescription, has been used in the treatment of, gout arthritis,
      arthralgia and inflammation. Since renal urate overload associated with severe
      disability including gout, elimination of excess renal uric acid is highly
      essential. Therefore, in this study we evaluated the antihyperuricemic and the
      renoprotective effect of the Shuang Qi gout capsule (SQ) with elucidation of its
      mechanism. MATERIALS AND METHODS: We assessed the antihyperuricemic activity of
      SQ on urinary and serum uric acid, creatinine, blood urea nitrogen, fractional
      excretion of uric acid (FEUA) and glomerular filtration rate of creatinine and
      uric acid in potassium oxonate (PO) - induced mice as well as in non-induced
      mice. To illuminate the mechanism of antihyperuricemic activity, we investigated
      renal transport activity and the expression of mRNA levels in PO-induced and non
      induced mice by western blot and RT-PCR methods. RESULTS: SQ showed significant
      reduction in serum uric acid, creatinine and blood urea nitrogen levels and
      marked elevation of urine uric acid, creatinine and FEUA levels only in
      hyperuricemic mice. Furthermore, SQ could recover the altered expressions of
      proteins and mRNA levels of all the main renal transporters significantly in dose
      dependent manner. CONCLUSIONS: SQ could effectively regulate the main renal
      transporters denoted its denote probable antihyperuricemic mechanism of SQ and
      its dose dependent uricosuric effect. In addition, SQ attenuated the deleterious
      effects of hyperuricemia with renal dysfunction. Thus SQ could be a potent
      antihyperuricemic agent which can perform as a safer and effective agent in the
      management of hyperuricemia via regulating the renal transporters.

PMID- 25614107
TI  - Food and medicine: Old traditions, novel opportunities.

PMID- 25614108
TI  - Integrated pharmacokinetics and biodistribution of multiple flavonoid C
      glycosides components in rat after oral administration of Abrus mollis extract
      and correlations with bio-effects.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Abrus mollis, a commonly used traditional Chinese
      medicine in China and other Asia countries, has been used clinically to prevent
      and treat hepatitis and alcoholic liver disease for decades. MATERIALS AND
      METHODS: A modified HPLC-MS method was developed for the determination of vicenin
      2 (AM-I), isoschaftoside (AM-II), and schaftoside (AM-III) of AM extract (AME) in
      rat plasma and tissues (heart, liver, spleen, lungs, and kidneys). Following oral
      administration of AME to rat at a dose of 200mg/kg, the concentrations of AM-I,
      II and III in plasma and tissues were quantified. An integrated double peak
      pharmacokinetics model was used to fit the concentration-time curves. The effects
      of drug on the bile flow and toe swelling of rats induced by carrageenan were
      also studied. RESULTS: The limit of quantitation of this modified HPLC-MS method
      decreased from 25 to 5ng/mL for plasma and from 100 to 10ng/g for tissue. These
      concentration-time curves show two successive maximum concentrations. The results
      of integrated double peak pharmacokinetics in this paper indicated that the three
      flavonoid C-glycosides may be absorbed by two sites of intestine in vivo. These
      results of bile flow and toe swelling showed a significant correlation between
      the pharmacokinetics and pharmacodynamics. CONCLUSIONS: The novel integrated
      double peak pharmacokinetic approach to studying the holistic pharmacokinetic
      properties of traditional Chinese medicine has been successfully developed and
      validated using AM as a model drug. This study would be a useful guide for the
      holistic double peak pharmacokinetic study in consistence with the intrinsic
      theory and characteristics of traditional Chinese medicine.

PMID- 25614110
TI  - Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL
      protease inhibitors.
AB  - The design and evaluation of a novel decahydroisoquinolin scaffold as an
      inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease
      (3CL(pro)) are described. Focusing on hydrophobic interactions at the S2 site,
      the decahydroisoquinolin scaffold was designed by connecting the P2 site
      cyclohexyl group of the substrate-based inhibitor to the main-chain at the alpha
      nitrogen atom of the P2 position via a methylene linker. Starting from a
      cyclohexene enantiomer obtained by salt resolution, trans-decahydroisoquinolin
      derivatives were synthesized. All decahydroisoquinolin inhibitors synthesized
      showed moderate but clear inhibitory activities for SARS 3CL(pro), which
      confirmed the fused ring structure of the decahydroisoquinolin functions as a
      novel scaffold for SARS 3CL(pro) inhibitor. X-ray crystallographic analyses of
      the SARS 3CL(pro) in a complex with the decahydroisoquinolin inhibitor revealed
      the expected interactions at the S1 and S2 sites, as well as additional
      interactions at the N-substituent of the inhibitor. 

PMID- 25614109
TI  - Saccharin: a lead compound for structure-based drug design of carbonic anhydrase
      IX inhibitors.
AB  - Carbonic anhydrase IX (CA IX) is a key modulator of aggressive tumor behavior and
      a prognostic marker and target for several cancers. Saccharin (SAC) based
      compounds may provide an avenue to overcome CA isoform specificity, as they
      display both nanomolar affinity and preferential binding, for CA IX compared to
      CA II (>50-fold for SAC and >1000-fold when SAC is conjugated to a carbohydrate
      moiety). The X-ray crystal structures of SAC and a SAC-carbohydrate conjugate
      bound to a CA IX-mimic are presented and compared to CA II. The structures
      provide substantial new insight into the mechanism of SAC selective CA isoform
      inhibition. 

PMID- 25614111
TI  - Rational design of specific binding hairpin Py-Im polyamides targeting human
      telomere sequences.
AB  - N-Methylpyrrole (Py)-N-methylimidazole (Im) polyamides are organic molecules that
      can recognize predetermined DNA sequences in a sequence-specific manner. Human
      telomeres contain regions of (TTAGGG)n repetitive nucleotide sequences at each
      end of chromosomes, and these regions protect the chromosome from deterioration
      or from fusion with neighboring chromosomes. The telomeres are disposable buffers
      at the ends of chromosomes that are truncated during cell division. Tandem
      hairpin Py-Im polyamide TH59, which recognizes human telomere sequences, was
      reported by Laemmli's group in 2001. Here, we synthesized three types of Py-Im
      polyamides 1-3 based on TH59 for specific recognition of human telomere repeat
      sequences. Thermal melting temperature (Tm) measurements and surface plasmon
      resonance analysis were used to evaluate the abilities of the three types of Py
      Im polyamides to discriminate between three kinds of DNA sequences.
      Significantly, the results showed that polyamides 1 and 2 have better affinities
      to TTAAGG than to TTAGGG. In contrast, polyamide 3 displayed good specificity to
      human telomere sequence, TTAGGG, as expected on the basis of Py-Im binding rules.

PMID- 25614112
TI  - Studies towards the synthesis of indolizin-5(3H)-one derivatives and related 6,5
      azabicyclic scaffolds by ring-closing metathesis.
AB  - Herein, we report on work towards the development of a new strategy for the
      synthesis of rare and biologically interesting indolizin-5(3H)-ones, which is
      based around the use of ring-closing metathesis to construct the carbocyclic ring
      system. This study has provided insights into the general stability of indolizin
      5(3H)-ones and their tendency to exist as the tautomeric indolizin-5-ols.
      Furthermore, this approach has allowed access to other novel structurally related
      compounds based around unusual 6,5-azabicyclic scaffolds, which are also
      difficult to generate using typical methods. The azabicyclic compounds
      synthesized in this study reside in attractive regions of heterocyclic chemical
      space that are underexploited in current drug and agrochemical discovery efforts.

PMID- 25614113
TI  - Synthesis and evaluation of a new Rhodamine B and Di(2-picolyl)amine conjugate as
      a highly sensitive and selective chemosensor for Al3+ and its application in
      living-cell imaging.
AB  - A new Rhodamine B derivative (RBDPA), namely, N(1)-(2-(3',6'-bis(diethylamino)-3
      oxospiro[isoindoline-1,9'-xanthen]-2-yl)ethyl)-N(4),N(4)-bis(pyridin-2
      ylmethyl)succinamide, was designed, synthesized and structurally characterized to
      develop a chemosensor. The studies show that RBDPA exhibits high sensitivity and
      selectivity toward Al(3+) among many other metal cations in an ethanol/H2O (1:1,
      v/v, pH=7.2, HEPES buffer, 0.1mM) solution. Fluorescence microscopy experiments
      further demonstrate that RBDPA can be used as a fluorescent probe to detect
      Al(3+) in living cells. 

PMID- 25614115
TI  - Discovery of 1-substituted benzyl-quinazoline-2,4(1H,3H)-dione derivatives as
      novel poly(ADP-ribose)polymerase-1 inhibitors.
AB  - Poly(ADP-ribose)polymerase-1 (PARP-1) has emerged as a promising anticancer drug
      target due to its key role in the DNA repair process. In this work, a novel
      series of 1-benzyl-quinazoline-2,4(1H,3H)-dione derivatives were designed and
      synthesized as human PARP-1 inhibitors, structure-activity relationships were
      conducted and led to a number of potent PARP-1 inhibitors having IC50 values of
      single or double digit nanomolar level. Compound 7j was a potent PARP-1 and PARP
      2 inhibitor and it could selectively kill the breast cancer cells MX-1 and MDA-MB
      468 with mutated BRCA1/2 and PTEN, respectively, in comparison with homologous
      recombination proficient cell types such as breast cancer cells MDA-MB-231. In
      addition, compound 7j displayed the strongest potentiation effect on temozolomide
      in MX-1 cells (PF50=3.77) in this series of PARP-1 inhibitors. 

PMID- 25614114
TI  - Novel, potent, orally bioavailable and selective mycobacterial ATP synthase
      inhibitors that demonstrated activity against both replicating and non
      replicating M. tuberculosis.
AB  - The mycobacterial F0F1-ATP synthase (ATPase) is a validated target for the
      development of tuberculosis (TB) therapeutics. Therefore, a series of eighteen
      novel compounds has been designed, synthesized and evaluated against
      Mycobacterium smegmatis ATPase. The observed ATPase inhibitory activities (IC50)
      of these compounds range between 0.36 and 5.45MUM. The lead compound 9d [N-(7
      chloro-2-methylquinolin-4-yl)-N-(3-((diethylamino)methyl)-4-hydroxyphenyl)-2,3
      dichlorobenzenesulfonamide] with null cytotoxicity (CC50>300MUg/mL) and excellent
      anti-mycobacterial activity and selectivity (mycobacterium ATPase IC50=0.51MUM,
      mammalian ATPase IC50>100MUM, and selectivity >200) exhibited a complete growth
      inhibition of replicating Mycobacterium tuberculosis H37Rv at 3.12MUg/mL. In
      addition, it also exhibited bactericidal effect (approximately 2.4log10
      reductions in CFU) in the hypoxic culture of non-replicating M. tuberculosis at
      100MUg/mL (32-fold of its MIC) as compared to positive control isoniazid
      [approximately 0.2log10 reduction in CFU at 5MUg/mL (50-fold of its MIC)]. The
      pharmacokinetics of 9d after p.o. and IV administration in male Sprague-Dawley
      rats indicated its quick absorption, distribution and slow elimination. It
      exhibited a high volume of distribution (Vss, 0.41L/kg), moderate clearance
      (0.06L/h/kg), long half-life (4.2h) and low absolute bioavailability (1.72%). In
      the murine model system of chronic TB, 9d showed 2.12log10 reductions in CFU in
      both lung and spleen at 173MUmol/kg dose as compared to the growth of untreated
      control group of Balb/C male mice infected with replicating M. tuberculosis
      H37Rv. The in vivo efficacy of 9d is at least double of the control drug
      ethambutol. These results suggest 9d as a promising candidate molecule for
      further preclinical evaluation against resistant TB strains. 

PMID- 25614116
TI  - Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists
      with antihypertensive activity.
AB  - A series of phenoxybutanoic acid derivatives were synthesized and tested for
      their antagonistic activity on the contraction of the rat thoracic aortic ring
      induced by endothelin-1. Preliminary screening results showed that 6e and 6g with
      benzoheterocycles demonstrated significant antagonistic activities when compared
      to the reference compound BQ123. The results from additional assays for the
      binding affinity and selectivity for endothelin receptors showed that 6e was a
      selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in
      relieving hypoxia-induced pulmonary arterial hypertension and right ventricular
      weight ratio. Therefore, 6e may have potential for further development as a
      therapeutic agent for the treatment of cardiovascular diseases. 

PMID- 25614117
TI  - Multifunctional scutellarin-rivastigmine hybrids with cholinergic, antioxidant,
      biometal chelating and neuroprotective properties for the treatment of
      Alzheimer's disease.
AB  - To discover multifunctional agents for the treatment of Alzheimer's disease (AD),
      a series of scutellarein carbamate derivatives were designed and synthesized
      based on the multitarget-directed ligand strategy. Their acetylcholinesterase and
      butyrylcholinesterase inhibitory activities, antioxidant activities, metal
      chelating properties and neuroprotective effects against hydrogen peroxide
      induced PC12 cell injury were evaluated in vitro. The results showed that most of
      the synthetic compounds exhibited good multifunctional activities. In particular,
      compound 15c exhibited dual inhibitory potency on acetylcholinesterase and
      butyrylcholinesterase with IC50 values of 0.57 and 22.6MUM, respectively, and
      good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c
      acted as a selective biometal chelator and possessed neuroprotective effects.
      Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had
      significant neuroprotective effects in scopolamine-induced cognitive impairment
      in mice. Taken together, these results suggest that compound 15c might be a
      potential multifunctional agent for the treatment of AD. 

PMID- 25614119
TI  - Sulfur-annulated hexa-peri-hexabenzocoronene decorated with phenylthio groups at
      the periphery.
AB  - The chemical nature of the edge periphery essentially determines the physical
      properties of graphene. As a molecular-level model system, large polycyclic
      aromatic hydrocarbons, that is, so-called nanographenes, can be chemically
      modified through either edge functionalization or doping with heteroatoms.
      Although the synthetic methods for edge substitution are well-developed,
      incorporation with heteroatoms by the bay annulation of large PAHs remains an
      enormous challenge. In this study, we present a feasible peripheral sulfur
      annulation of hexa-peri-hexabenzocoronene (HBC) by thiolation of perchlorinated
      HBC. The tri-sulfur-annulated HBC and di-sulfur-annulated HBC decorated with
      phenylthio groups were obtained and characterized by X-ray diffraction, revealing
      their distinct sulfur-annulated peripheral structure. Associated with theoretical
      calculations, we propose that the regioselective sulfur annulation results from
      the minimization of strain in the aromatic backbone. We further demonstrate the
      structure-correlated property modulation by sulfur annulation, manifested by a
      decrease in band gap and tunable redox activity. 

PMID- 25614118
TI  - Structure-activity relationship study of diphenylamine-based estrogen receptor
      (ER) antagonists.
AB  - We have reported the design and synthesis of novel estrogen receptor (ER)
      agonists with a diphenylamine skeleton, which has several advantages over the
      formerly used diphenylmethane skeleton for drug development. Here, we confirmed
      the versatility of the diphenylamine skeleton by designing and synthesizing ER
      antagonist candidates bearing a basic alkylamino side chain on one of the two
      phenol groups of the diphenylamine agonist core structure. Among the tested
      compounds, cyclic alkylamine-containing derivatives showed more potent ER
      antagonistic activity than the corresponding acyclic derivatives in cell
      proliferation assay using the MCF-7 cell line. Compound 5e showed the most potent
      antiestrogenic activity (IC50: 1.3*10(-7)M), being 10times more potent than
      tamoxifen. 

PMID- 25614120
TI  - Occurrence of Ixodiphagus hookeri (Hymenoptera: Encyrtidae) in Ixodes ricinus
      (Acari: Ixodidae) in southern Italy.
AB  - Natural enemies of ticks include the parasitoid wasp Ixodiphagus hookeri
      (Hymenoptera: Encyrtidae). The aim of this preliminary study was to investigate
      the occurrence of I. hookeri DNA in a community of ticks (Ixodes ricinus,
      Dermacentor marginatus, Hyalomma marginatum, Haemaphysalis inermis and
      Rhipicephalus turanicus). From May 2010 to March 2012, ticks were collected
      monthly by dragging and flagging, identified, and 481 adults and 305 nymphs
      screened molecularly for infection with I. hookeri. Of the samples tested
      (n=786), 3.1% (n=25) were positive for I. hookeri DNA, 7.2% (n=22) in nymphs and
      0.6% (n=3) in adults. I. hookeri DNA was only detected in I. ricinus. This study
      shows that I. hookeri infests I. ricinus in southern Italy, with nymphs being the
      main developmental stage affected by this wasp. 

PMID- 25614121
TI  - Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin
      resistance by inducing fibroblast growth factor 21.
AB  - The aryl hydrocarbon receptor (AHR), also known as the dioxin receptor, was
      originally characterized as a xenobiotic receptor that senses xenotoxicants. We
      investigated the endobiotic and hepatic role of AHR in fatty liver and energy
      metabolism and identified the endocrine factor that mediates the metabolic
      function of AHR. Wild-type and liver-specific constitutively activated human AHR
      transgenic mice were used to investigate the role of AHR in fatty liver and
      energy homeostasis. Adenovirus expressing short hairpin RNA targeting fibroblast
      growth factor 21 (FGF21) were used to determine the involvement of FGF21 in the
      metabolic effect of AHR. We showed that, despite their severe fatty liver, the
      transgenic mice were protected from diet-induced obesity and type 2 diabetes. We
      identified the endocrine hormone FGF21 as a mediator for the metabolic benefit of
      AHR and established FGF21 as a direct transcriptional target of AHR.
      Interestingly, the transactivation of FGF21 by AHR contributed to both hepatic
      steatosis and systemic insulin hypersensitivity, both of which were largely
      abolished upon FGF21 knockdown. CONCLUSIONS: The AHR-FGF21 endocrine signaling
      pathway establishes AHR as a pivotal environmental modifier that integrates
      signals from chemical exposure in the regulation of lipid and energy metabolism.

PMID- 25614122
TI  - Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its
      associated carbohydrates in lung metastasis.
AB  - PURPOSE: Expression of lysosome-associated membrane protein-1 (LAMP1) on the
      surface correlates with metastatic potential of B16 melanoma cells.
      Downregulation of their expression in high metastatic (B16F10) cells reduced
      their surface expression and metastatic potential. Present investigations explore
      if overexpression of LAMP1 on the surface of low metastatic (B16F1) cells augment
      their metastatic ability, and if so, how? METHODS: B16F1 cells were transduced
      with lentiviral vector carrying mutant-LAMP1 (Y386A) (mutLAMP1). Surface
      expression of LAMP1 and carbohydrates was analyzed by flow cytometry,
      immunofluorescence and/or immunoprecipitation and Western blotting. Cell
      spreading and motility were assessed on components of extracellular matrix (ECM)
      (fibronectin) and basement membrane (BM) (matrigel), and galectin-3-coated
      coverslips/plates. Metastatic potential was assessed using experimental
      metastasis assay. RESULTS: Pre-incubation with anti-LAMP1 antibodies
      significantly reduced lung metastasis of B16F10 cells. Overexpression of mutLAMP1
      significantly increased its surface expression on B16F1 cells, resulting in
      increased cellular spreading and motility on fibronectin and matrigel. LAMP1 is
      the major carrier of poly-N-acetyllactosamine (polyLacNAc) on B16F10 cells.
      However, significantly higher expression of mutLAMP1 had no effect on galectin-3
      binding on cell surface or on spreading or motility of cells on galectin-3-coated
      coverslips/plates. These cells also failed to show any gain in metastatic
      ability. This could be because LAMP1 from these cells carried significantly lower
      levels of polyLacNAc in comparison with B16F10 cells. CONCLUSIONS: PolyLacNAc on
      B16F10 cells and galectin-3 on lungs are the major participants in melanoma
      metastasis. Although surface LAMP1 promotes interactions with organ ECM and BM,
      carbohydrates on LAMP1 play a decisive role in dictating lung metastasis.

PMID- 25614123
TI  - Complex forest dynamics indicate potential for slowing carbon accumulation in the
      southeastern United States.
AB  - Over the past century forest regrowth in Europe and North America expanded forest
      carbon (C) sinks and offset C emissions but future C accumulation is uncertain.
      Policy makers need insights into forest C dynamics as they anticipate emissions
      futures and goals. We used land use and forest inventory data to estimate how
      forest C dynamics have changed in the southeastern United States and attribute
      changes to land use, management, and disturbance causes. From 2007-2012, forests
      yielded a net sink of C because of net land use change (+6.48 Tg C yr(-1)) and
      net biomass accumulation (+75.4 Tg C yr(-1)). Forests disturbed by weather,
      insect/disease, and fire show dampened yet positive forest C changes (+1.56,
      +1.4, +5.48 Tg C yr(-1), respectively). Forest cutting caused net decreases in C
      (-76.7 Tg C yr(-1)) but was offset by forest growth (+143.77 Tg C yr(-1)). Forest
      growth rates depend on age or stage of development and projected C stock changes
      indicate a gradual slowing of carbon accumulation with anticipated forest aging
      (a reduction of 9.5% over the next five years). Additionally, small shifts in
      land use transitions consistent with economic futures resulted in a 40.6%
      decrease in C accumulation. 

PMID- 25614124
TI  - Creating a new ethical climate for drug research in children and pregnant women.

PMID- 25614125
TI  - Is glutamine deficiency the link between inflammation, malnutrition, and fatigue
      in cancer patients?
AB  - PURPOSE: Evaluation of potential associations between plasma glutamine levels and
      the incidence of cancer related fatigue, physical performance, poor nutritional
      status, and inflammation in patients with solid tumors. STUDY DESIGN: Mono-center
      cross-sectional study recruiting 100 (34 women) consecutive patients (September
      2009-March 2011; >=18 y) with solid tumors and causal tumor therapy. METHODOLOGY:
      Fasting venous blood was harvested for routine clinical chemistry, amino acid
      (HPLC) and inflammation marker analyses. Clinical assessments included global,
      physical, affective and cognitive fatigue (questionnaire) and Karnofsky
      performance status. Nutritional status was evaluated using bioelectrical
      impedance analysis, the Prognostic Inflammatory and Nutritional Index and plasma
      protein levels. Regression analyses were performed to correlate continuous
      variables with plasma glutamine (95% confidence intervals). RESULTS: Nutritional
      status was impaired in 19% of the patients. Average plasma glutamine
      concentration (574.0 +/- 189.6 MUmol/L) was within normal range but decreased
      with impaired physical function. Plasma glutamine was linked to the ratio
      extracellular to body cell mass (p < 0.044), CRP (p < 0.001), physical (p =
      0.014), affective (p = 0.041), and global fatigue (p = 0.030). Markers of
      inflammation increased with low physical performance. CONCLUSIONS: The data
      support our working hypothesis that in cancer patients systemic inflammation
      maintains a catabolic situation leading to malnutrition symptoms and glutamine
      deprivation, the latter being associated with cancer related fatigue.

PMID- 25614126
TI  - Dietary plant stanols or sterols neither accumulate in stenotic aortic valves nor
      influence their structure or inflammatory status.
AB  - BACKGROUND & AIMS: Consumption of plant stanols and plant sterols decreases LDL
      cholesterol level and increases serum concentrations of plant stanols/sterols,
      but it is practically unexplored whether also their tissue concentrations
      increase. Thus, the aim of this study was to assess whether consuming plant
      stanols/sterols increases their concentrations in stenotic aortic valves and
      affect the valvular structure (collagen and elastin) or inflammation (macrophages
      and mast cells). METHODS: In a randomized, double-blind controlled intervention
      patients with severe aortic stenosis consumed margarine without (n = 11) or with
      2 g of plant stanols (n = 12) or sterols (n = 13) until valve replacement surgery
      (2.6 months, on average). The effects of sitostanol and sitosterol on the
      expression and secretion of proinflammatory cytokines by cultured aortic valve
      myofibroblasts were also assessed. RESULTS: Control-related LDL-cholesterol was
      diminished by 16% (p < 0.05) by plant stanol and by 11% (NS) by plant sterol
      consumption, respectively. In the resected valves, cholesterol, plant stanol and
      sterol levels were similar in all groups. Consumed plant stanols or sterols had
      no effect on valvular structure or mast cell or macrophage numbers in valves.
      Incubation of cultured myofibroblasts derived from stenotic valves with
      sitostanol or sitosterol decreased mRNA expression of the monocyte chemotactic
      protein-1 (p < 0.05) and interleukin-1 beta (p < 0.05). CONCLUSIONS: In this
      study, plant stanol/sterol consumption did not affect cholesterol, plant stanol
      or sterol levels in stenotic aortic valves; neither did they influence the
      structure or the inflammatory status of the valves. However, these findings need
      to be confirmed in a larger-scale intervention. ClinicalTrials.govRegister
      #NCT00738933.

PMID- 25614127
TI  - Dementia severity and the longitudinal costs of informal care in the Cache County
      population.
AB  - BACKGROUND: Dementia costs are critical for influencing healthcare policy, but
      limited longitudinal information exists. We examined longitudinal informal care
      costs of dementia in a population-based sample. METHODS: Data from the Cache
      County Study included dementia onset, duration, and severity assessed by the Mini
      Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), and
      Neuropsychiatric Inventory (NPI). Informal costs of daily care (COC) was
      estimated based on median Utah wages. Mixed models estimated the relationship
      between severity and longitudinal COC in separate models for MMSE and CDR.
      RESULTS: Two hundred and eighty-seven subjects (53% female, mean (standard
      deviation) age was 82.3 (5.9) years) participated. Overall COC increased by 18%
      per year. COC was 6% lower per MMSE-point increase and compared with very mild
      dementia, COC increased over twofold for mild, fivefold for moderate, and sixfold
      for severe dementia on the CDR. CONCLUSIONS: Greater dementia severity predicted
      higher costs. Disease management strategies addressing dementia progression may
      curb costs.

PMID- 25614128
TI  - Long-term seizure and psychosocial outcomes after resective surgery for
      intractable epilepsy.
AB  - Resective surgery is considered an effective treatment for refractory
      localization-related epilepsy. Most studies have reported seizure and
      psychosocial outcomes of 2-5 years postsurgery and a few up to 10 years. Our
      study aimed to assess long-term (up to 15 years) postsurgical seizure and
      psychosocial outcomes at our epilepsy center. The Henry Ford Health System
      Corporate Data Store was accessed to identify patients who had undergone surgical
      resection for localization-related epilepsy from 1993 to 2011. Demographics
      including age at epilepsy onset and surgery, seizure frequency before surgery,
      and pathology were gathered from electronic medical records. Phone surveys were
      conducted from May 2012 to January 2013 to determine patients' current seizure
      frequency and psychosocial metrics including driving and employment status and
      use of antidepressants. Surgical outcomes were based on Engel's classification
      (classes I and II=favorable outcomes). McNemar's tests, chi-square tests, two
      sample t-tests, and Wilcoxon two sample tests were used to analyze the
      relationships of psychosocial and surgical outcomes with demographic and surgical
      characteristics. A total of 470 patients had resective epilepsy surgery, and of
      those, 50 (11%) had died since surgery. Of the remaining, 253 (60%) were
      contacted with mean follow-up of 10.6+/-5.0years (27% of patients had follow-up
      of 15 years or longer). Of the patients surveyed, 32% were seizure-free and 75%
      had a favorable outcome (classes I and II). Favorable outcomes had significant
      associations with temporal resection (78% temporal vs 58% extratemporal, p=0.01)
      and when surgery was performed after scalp EEG only (85% vs 65%, p<0.001). Most
      importantly, favorable and seizure-free outcome rates remained stable after
      surgery over long-term follow-up [i.e., <5 years (77%, 41%), 5-10 years (67%,
      29%), 10-15 years (78%, 38%), and >15 years (78%, 26%)]. Compared to before
      surgery, patients at the time of the survey were more likely to be driving (51%
      vs 35%, p<0.001) and using antidepressants (30% vs 22%, p=0.013) but less likely
      to be working full-time (23% vs 42%, p<0.001). A large majority of patients (92%)
      considered epilepsy surgery worthwhile regardless of the resection site, and this
      was associated with favorable outcomes (favorable=98% vs unfavorable=74%,
      p<0.001). The findings suggest that resective epilepsy surgery yields favorable
      long-term postoperative seizure and psychosocial outcomes.

PMID- 25614129
TI  - Effects of a liquid diet on the temporomandibular joint of growing rats.
AB  - OBJECTIVE: The aim of the present study was to clarify the effects of a liquid
      diet on the temporomandibular joint (TMJ) in growing rats. MATERIALS AND METHODS:
      Twenty-four male Wistar rats were weaned at 21 days and divided into control and
      experimental groups (12 in each group). Control rats were fed a solid diet and
      experimental rats were fed a liquid diet from 1 to 8 weeks. After injection with
      5-bromo-2'-deoxyuridine (BrdU), the animals were perfused and the heads were
      removed. Serial coronal sections of the TMJ were stained with hematoxylin and
      eosin, or BrdU immunohistochemistry was done (12 rats in each group). Three
      dimensions and the thicknesses of the cartilage layers of the TMJ were measured,
      and cell proliferation in the TMJ was examined. RESULTS: After 4 weeks, the
      height and width of the mandibular fossa and the width and length of the
      mandibular condyle were smaller in the experimental groups than in the control
      groups. The cartilage layer in these areas was also thinner at 4 weeks. The BrdU
      levels in the intermediate zone of the mandibular fossa (at 4 weeks) and the
      mandibular condyle (at 1 and 4 weeks) were lower in the experimental groups than
      in the controls. CONCLUSION: These findings suggest that the growth of the
      mandibular fossa and mandibular condyle of rats was inhibited by the low
      proliferative activity of intermediate zone cells induced by liquid feeding.

PMID- 25614130
TI  - Influence of computer work under time pressure on cardiac activity.
AB  - Computer users are often under stress when required to complete computer work
      within a required time. Work stress has repeatedly been associated with an
      increased risk for cardiovascular disease. The present study examined the effects
      of time pressure workload during computer tasks on cardiac activity in 20 healthy
      subjects. Heart rate, time domain and frequency domain indices of heart rate
      variability (HRV) and Poincare plot parameters were compared among five computer
      tasks and two rest periods. Faster heart rate and decreased standard deviation of
      R-R interval were noted in response to computer tasks under time pressure. The
      Poincare plot parameters showed significant differences between different levels
      of time pressure workload during computer tasks, and between computer tasks and
      the rest periods. In contrast, no significant differences were identified for the
      frequency domain indices of HRV. The results suggest that the quantitative
      Poincare plot analysis used in this study was able to reveal the intrinsic
      nonlinear nature of the autonomically regulated cardiac rhythm. Specifically,
      heightened vagal tone occurred during the relaxation computer tasks without time
      pressure. In contrast, the stressful computer tasks with added time pressure
      stimulated cardiac sympathetic activity.

PMID- 25614131
TI  - Second language syntactic processing revealed through event-related potentials:
      an empirical review.
AB  - Learning a second language (L2) can be crucial in the present globalized society.
      However, reaching the level of L1 performance of native speakers is still a
      challenge for many. Distinct factors could account for the persistent gap
      observed between natives' and non-natives' syntactic abilities: L1-L2
      differences, AoA, proficiency, L2 immersion duration, L2 training duration.
      Although different theoretical approaches described the role of these several
      factors, not all studies using on-line measures have investigated them
      comprehensively and consistently. The present work reviews available ERP studies
      on L2 syntactic analysis in order to establish the relative weight of each factor
      on the time course of L2 processing. Logistic regression analyses were performed
      on the presence or absence of ERP effects reported in response to L2 syntactic
      violations, including all the influential factors as categorical independent
      variables. The results showed that immersion duration has an influence on the ERP
      correlates linked to early mechanisms of syntactic processing, while the global
      proficiency level has an impact on the ERP correlates related to late, language
      monitoring activity. 

PMID- 25614133
TI  - Immediate effects of low-intensity laser (808 nm) on fatigue and strength of
      spastic muscle.
AB  - The cerebrovascular accident (CVA), high-impact disease II, affects the basic
      functions of the limbs, leading to changes of sensory, language, and motor
      functions. The search for resources that minimize the damage caused by this
      disease grows every day. The clinical use of low-intensity laser therapy (LILT)
      has provided major breakthroughs in the treatment of muscular disorders and
      prevention of muscle fatigue. Thus, the objective of the present study is to
      analyze the answers and immediate adaptations of the rectus femoris and vastus
      medialis of spastic hemiparetic patients, facing the increase in peak torque and
      triggering muscle fatigue, after application of LILT. Double-blind clinical
      trials were conducted with 15 volunteers post-CVA with spasticity, of both
      genders, between 40 and 80 years old. To this end, the volunteers went through
      three consecutive stages of rating (control, placebo, and laser). All performed
      tests of isometric contraction on the patient's hemiparetic side. Significant
      differences were observed with regard to the increase in muscle performance (p =
      0.0043) and the reduction in blood lactate concentration (p < 0.0001) of the post
      LILT muscles. The LILT (diode laser, l100 mW 808 nm, 4.77 J/cm(2)/point, 40 s/AP)
      can be employed during and after spastic muscle-strengthening exercises,
      contributing to the improvement of motor function of the patient. After
      application of LILT, we found increased torque as well as decreased in lactate
      level in patients with spasticity.

PMID- 25614132
TI  - In vivo assessment of neurotransmitters and modulators with magnetic resonance
      spectroscopy: application to schizophrenia.
AB  - In vivo measurement of neurotransmitters and modulators is now feasible with
      advanced proton magnetic resonance spectroscopy ((1)H MRS) techniques. This
      review provides a basic tutorial of MRS, describes the methods available to
      measure brain glutamate, glutamine, gamma-aminobutyric acid, glutathione, N
      acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3T or
      higher, and summarizes the neurochemical findings in schizophrenia. Overall, (1)H
      MRS holds great promise for producing biomarkers that can serve as treatment
      targets, prediction of disease onset, or illness exacerbation in schizophrenia
      and other brain diseases. 

PMID- 25614135
TI  - Gastrointestinal bleeding with continuous-flow left ventricular assist devices.
AB  - Continuous-flow left ventricular assist device (CF-LVAD) insertion is a life
      saving procedure that is being increasingly used in patients with advanced heart
      failure. However, patients with CF-LVADs are at an increased risk of
      gastrointestinal bleeding (GIB). Bleeding can occur anywhere in the GI tract with
      lesions being more prevalent in the upper GI tract than in the lower GI tract.
      The pathophysiology of GIB in patients with CF-LVADs is unique and likely
      involves three synergistic mechanisms-coagulopathy, acquired von Willebrand
      disease and continuous non-pulsatile blood flow. Management strategies vary
      depending on the presentation and site of bleeding. Prevention strategies to
      prevent GIB in these patients include low pump speed, close hemodynamic
      monitoring and a low threshold for endoscopy. We aim to review in detail the
      pathophysiology, management, complications and preventive strategies in patients
      with CF-LVAD who present with GIB.

PMID- 25614134
TI  - Effectiveness of high-intensity laser therapy and splinting in lateral
      epicondylitis; a prospective, randomized, controlled study.
AB  - Lateral epicondylitis (LE) is a common disorder that causes pain on the outside
      of the elbow, as well as pain and weakness during gripping. In this prospective,
      randomized, controlled, assessor-blinded trial, we planned to investigate the
      effects of high-intensity laser therapy (HILT) in patients with LE and to compare
      these results with those of a brace and placebo HILT. Patients were randomly
      assigned to three treatment groups. The first group was treated with HILT. The
      second group (sham therapy group) received placebo HILT, while the third group
      (brace group) used the lateral counterforce brace for LE. The patients were
      assessed for grip strength, pain, disability, and quality of life. Outcome
      measurements and ultrasonographic examination of the patients were performed
      before treatment (week 0) and after treatment (after 4 and 12 weeks). HILT and
      brace groups showed significant improvements for most evaluation parameters (pain
      scores, grip strength, disability scores, and several subparts of the short-form
      36 health survey (physical function, role limitations due to physical
      functioning, bodily pain, general health, and vitality)) after treatment (after 4
      and 12 weeks). However, the improvements in evaluation parameters of the patients
      with LE in HILT and brace groups were not reflected to ultrasonographic findings.
      Furthermore, comparison of the percentage changes of the parameters after
      treatment relative to pretreatment values did not show a significant difference
      between HILT and brace groups. We conclude that HILT and splinting are effective
      physical therapy modalities for patients with LE in reducing pain and improving
      disability, quality of life, and grip strength.

PMID- 25614136
TI  - Retrospective analysis of the incidence of epidural haematoma in patients with
      epidural catheters and abnormal coagulation parameters.
AB  - BACKGROUND: Epidural haematoma is a rare but potentially catastrophic
      complication associated with epidural catheterization. The times of insertion and
      removal of epidural catheters are high-risk periods for epidural haematoma
      formation, especially with abnormal coagulation parameters. There is a lack of
      data on the incidence of epidural haematoma in patients with abnormal coagulation
      parameters. METHODS: A retrospective analysis was undertaken from 2002 to 2009 on
      patients with an epidural catheter. Queries were performed on the coagulation
      parameters for the dates of placement and removal of the catheters and on all
      documented epidural haematoma cases. RESULTS: During the study period, 11 600
      epidural catheters were placed. In the setting of abnormal coagulation
      parameters, 278 (2.4%) epidural catheters were placed and 351 (3%) were removed.
      Two epidural haematomas occurred; both patients had epidural catheters and spinal
      drains placed for vascular procedures with abnormal coagulation parameters after
      operatation. The haematomas occurred after removal of the catheters. Based on our
      study, the incidence of epidural haematoma in patients with abnormal coagulation
      parameters is 1 in 315 patients, with the lower limit of the 95% confidence
      interval at 87 and the upper limit at 2597. CONCLUSIONS: The risk of epidural
      haematoma is clearly elevated with abnormal coagulation parameters. Our data
      suggest that as the incidence of epidural haematoma with neuraxial access in
      patients with abnormal coagulation is not 100%, individual risk-benefit
      evaluations are warranted.

PMID- 25614137
TI  - PscI is a type III secretion needle anchoring protein with in vitro
      polymerization capacities.
AB  - The export of bacterial toxins across the bacterial envelope requires the
      assembly of complex, membrane-embedded protein architectures. Pseudomonas
      aeruginosa employs type III secretion (T3S) injectisome to translocate exotoxins
      directly into the cytoplasm of a target eukaryotic cell. This multi-protein
      channel crosses two bacterial membranes and extends further as a needle through
      which the proteins travel. We show in this work that PscI, proposed to form the
      T3S system (T3SS) inner rod, possesses intrinsic properties to polymerize into
      flexible and regularly twisted fibrils and activates IL-1beta production in mouse
      bone marrow macrophages in vitro. We also found that point mutations within C
      terminal amphipathic helix of PscI alter needle assembly in vitro and T3SS
      function in cell infection assays, suggesting that this region is essential for
      an efficient needle assembly. The overexpression of PscF partially compensates
      for the absence of the inner rod in PscI-deficient mutant by forming a secretion
      proficient injectisome. All together, we propose that the polymerized PscI in P.
      aeruginosa optimizes the injectisome function by anchoring the needle within the
      envelope-embedded complex of the T3S secretome and - contrary to its counterpart
      in Salmonella - is not involved in substrate switching. 

PMID- 25614138
TI  - Cloning, expression and characterization of a putative 2,5-diketo-D-gluconic acid
      reductase in Comamonas testosteroni.
AB  - Aldo-keto reductases (AKRs) are a superfamily of soluble NAD(P)(H)
      oxidoreductases. The function of the enzymes is to reduce aldehydes and ketones
      into primary and secondary alcohols. We have cloned a 2,5-diketo-D-gluconic acid
      reductase (2,5DKGR) gene from Comamonas testosteroni (C. testosteroni) ATCC11996
      (a Gram-negative bacterium which can use steroids as carbon and energy source)
      into plasmid pET-15b and over expressed in Escherichia coli BL21 (DE3). The
      protein was purified by His-tag Metal chelating affinity chromatography column.
      The 2,5-diketo-D-gluconic acid reductase (2,5DKGR) gene contains 1062 bp and
      could be translated into a protein of 353 amino acid residues. Three consensus
      sequences of the AKR superfamily are found as GxxxxDxAxxY, LxxxGxxxPxxGxG and
      LxxxxxxxxxDxxxxH. GxxxxDxAxxY is the active site, LxxxGxxxPxxGxG is the Cofactor
      binding site for NAD(P)(H), LxxxxxxxxxDxxxxH is used for supporting the 3D
      structure. 2,5-diketo-D-gluconic acid reductase gene of C. testosteroni was
      knocked out and a mutant M-AKR was obtained. Compared to wild type C.
      testosteroni, degradations of testosterone, estradiol, oestrone and
      methyltestosterone in mutant M-AKR were decreased. Therefore, 2,5-diketo-D
      gluconic acid reductase in C. testosteroni is involved in steroid degradation.

PMID- 25614139
TI  - Development of an innovative process evaluation approach for the Families
      Improving Together (FIT) for weight loss trial in African American adolescents.
AB  - This study demonstrates how a multi-theoretical, multilevel process evaluation
      was used to assess implementation of the Families Improving Together (FIT) for
      weight loss intervention. FIT is a randomized controlled trial evaluating a
      culturally tailored, motivational plus family-based program on weight loss in
      African American adolescents and their parents. Social Cognitive, Self
      Determination, Family Systems theories and cultural tailoring principles guided
      the conceptualization of essential elements across individual/family,
      facilitator, and group levels. Data collection included an observational rating
      tool, attendance records, and a validated psychosocial measure. RESULTS:
      Attendance records (0=absent, 1=present, criteria=>=70%) indicated that 71.5% of
      families attended each session. The survey (1=false, 6=true, criteria=>=4.5)
      indicated that participants perceived a positive group climate (M=5.16, SD=0.69).
      A trained evaluator reported that facilitator dose delivered (0=no, 1=yes,
      criteria=>=75%) was high (99.6%), and fidelity (1=none to 4=all, criteria=>=3)
      was adequate at facilitator (M=3.63, SD=0.41) and group levels (M=3.35, SD=0.49).
      Five cultural topics were raised by participants related to eating (n=3) and
      physical activity (n=2) behaviors and were integrated as part of the final
      curriculum. DISCUSSION: Results identify areas for program improvement related to
      delivery of multi-theoretical and cultural tailoring elements. Findings may
      inform future strategies for implementing effective weight loss programs for
      ethnic minority families.

PMID- 25614140
TI  - Modulation of bone's sensitivity to low-intensity vibrations by acceleration
      magnitude, vibration duration, and number of bouts.
AB  - Variables defining vibration-based biomechanical treatments were tested by their
      ability to affect the musculoskeleton in the growing mouse. Duration of a
      vibration bout, but not variations in vibration intensity or number of vibration
      bouts per day, was identified as modulator of trabecular bone formation rates.
      INTRODUCTION: Low-intensity vibrations (LIV) may enhance musculoskeletal
      properties, but little is known regarding the role that individual LIV variables
      play. We determined whether acceleration magnitude and/or the number and duration
      of daily loading bouts may modulate LIV efficacy. METHODS: LIV was applied to 8
      week-old mice at either 0.3 g or 0.6 g for three weeks; the number of daily bouts
      was one, two, or four, and the duration of a single bout was 15, 30, or 60 min. A
      frequency of 45 Hz was used throughout. RESULTS: LIV induced tibial cortical
      surface strains in 4-month-old mice of approximately 10 MUepsilon at 0.3 g and 30
      MUepsilon at 0.6 g. In trabecular bone of the proximal tibial metaphysis, all
      single daily bout signal combinations with the exception of a single 15 min daily
      bout at 0.3 g (i.e., single bouts of 30 and 60 min at 0.3 g and 15 and 30 min at
      0.6 g) produced greater bone formation rates (BFR/BS) than in controls. Across
      all signal combinations, 30 and 60 min bouts were significantly more effective
      than 15 min bouts in raising BFR/BS above control levels. Increasing the number
      of daily bouts or partitioning a single daily bout into several shorter bouts did
      not potentiate efficacy and in some instances led to BFR/BS that was not
      significantly different from those in controls. Bone chemical and muscle
      properties were similar across all groups. CONCLUSIONS: These data may provide a
      basis towards optimization of LIV efficacy and indicate that in the growing mouse
      skeleton, increasing bout duration from 15 to 30 or 60 min positively influences
      BFR/BS.

PMID- 25614141
TI  - US Preventative Services Task Force FRAX threshold has a low sensitivity to
      detect osteoporosis in women ages 50-64 years.
AB  - The US Preventative Services Task Force (USPSTF) recommends consideration for
      screening for osteoporosis in women under age 65 who have an estimated 10-year
      major osteoporotic fracture risk of 9.3 % or higher. We found that this threshold
      for osteoporosis screening in women ages 50-64 years old has a low sensitivity to
      detect osteoporosis. INTRODUCTION: The US Preventative Services Task Force
      (USPSTF) recommends consideration of dual-energy X-ray absorptiometry (DXA) in
      women under ages 50-64 with a major osteoporotic fracture (MOF) risk of 9.3 % or
      higher, as estimated by the fracture risk assessment tool (FRAX) tool. We
      assessed the performance of the 9.3 % MOF risk threshold for detecting
      osteoporosis and evaluated whether DXA indication appeared appropriate, based on
      USPSTF criteria and other risk factors, at our institution. METHODS: We performed
      a retrospective record review of women ages 50-64.5 years old to determine
      clinical factors and FRAX scores of women undergoing a DXA at our institution
      over a 6-month period after the USPSTF recommendations were released and
      evaluated the sensitivity and specificity of the 9.3 % MOF threshold to detect
      densitometric osteoporosis. Additionally, using the USPSTF criteria and several
      additional risk factors, we evaluated the extent of potentially inappropriate DXA
      use in women ages 50 to 64 years in a large primary care practice in an academic
      medical center. RESULTS: The analysis included 465 DXA tests. The overall
      sensitivity and specificity of a FRAX-calculated MOF risk >=9.3 % was 37 and 74
      %, respectively, for the detection of osteoporosis. The receiver operator
      characteristic curve (ROC) demonstrated an area under the curve of 0.58. Lowering
      the FRAX risk threshold to 5.5 % would increase the sensitivity of detecting
      osteoporosis in our population from 37 to 80 % while reducing the specificity
      from 74 to 27 %. Out of 465 DXAs, 371 (79.8 %) were classified as appropriately
      ordered per our pre-specified criteria. Of the 120 women with osteoporosis at the
      hip and/or spine based on T-score values of -2.5 or less, 14 DXAs (11.7 %) were
      classified as potentially inappropriate based on a FRAX-predicted MOF risk less
      than 9.3 % and lack of additional pre-specified risk factors. CONCLUSION: We
      found that the USPSTF-recommended MOF risk threshold of 9.3 % for osteoporosis
      screening in women ages 50-64 years old has a low sensitivity to detect
      osteoporosis.

PMID- 25614142
TI  - Stimulation of suicidal erythrocyte death by PRIMA-1.
AB  - BACKGROUND: The anticarcinogenic drug PRIMA-1 (p53 reactivation and induction of
      massive apoptosis 1) induces suicidal death of tumor cells, an effect in large
      part attributed to the up-regulation of the proapoptotic transcription factor
      p53. Erythrocytes are lacking gene transcription but are nevertheless able to
      enter eryptosis, a suicidal erythrocyte death characterized by cell shrinkage and
      cell membrane scrambling with phosphatidylserine translocation to the erythrocyte
      surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity
      ([Ca(2+)]i) and ceramide formation. The present study tested whether PRIMA-1
      stimulates eryptosis. METHODS: Phosphatidylserine exposure at the cell surface
      was estimated from annexin V binding, cell volume from forward scatter, [Ca(2+)]i
      from Fluo3-fluorescence, ceramide abundance from binding of specific antibodies,
      and ROS formation from DCFDA fluorescence. RESULTS: A 48 h exposure of human
      erythrocytes to PRIMA-1 (25 uM) significantly increased the percentage of annexin
      V-binding cells without significantly influencing [Ca(2+)]i or forward scatter.
      PRIMA-1 (100 uM) induced annexin-V-binding was not significantly blunted by
      removal of extracellular Ca(2+) or by the caspase-3 inhibitor zVAD. PRIMA-1 (100
      uM) further increased the ceramide abundance at the cell surface and ROS
      formation. CONCLUSIONS: PRIMA-1 stimulates phosphatidylserine translocation at
      the erythrocyte cell membrane, an effect at least partially due to up-regulation
      of ceramide abundance and ROS formation.

PMID- 25614143
TI  - Incorporating the patient's voice into electronic health records through patient
      reported outcomes as the "review of systems".
AB  - Owing to lack of standardization for eliciting patient symptoms, the limited time
      available during clinical encounters, and the often-competing priorities of
      patients and providers, providers may not appreciate the full spectrum of the
      patient's symptom experience. Using electronically collected patient-reported
      outcomes to capture the review of system outside of the clinic visit may not only
      improve the efficiency, completeness, and accuracy of data collection for the
      review of system, but also provide the opportunity to operationalize
      incorporating the patient's voice into the electronic health record. While the
      necessary technology is already available, multiple stakeholders, including
      electronic health record vendors, clinicians, researchers, and professional
      societies, need to align their interests before this can become a widespread
      reality. 

PMID- 25614144
TI  - A pharmacokinetic comparison of anrukinzumab, an anti- IL-13 monoclonal antibody,
      among healthy volunteers, asthma and ulcerative colitis patients.
AB  - AIMS: Anrukinzumab is an anti-IL13 monoclonal antibody. The goals of this study
      are to characterize the pharmacokinetics of anrukinzumab in healthy volunteers
      and different disease states and to identify covariates. METHODS: A population
      pharmacokinetic (PK) model was developed in NONMEM, using data from five clinical
      studies including healthy volunteers, asthma and ulcerative colitis (UC)
      patients. Different dosing regimens including different routes of administration
      were also included in the data. RESULTS: The PK of anrukinzumab were described by
      a two compartment model with first order absorption and elimination. The
      population estimates (relative standard error) of the volumes of distribution in
      the central (Vc ) and peripheral (Vp ) compartments were 3.8 (4.6%) and 2.2 l
      (8.7%), respectively. In non-UC patients, the population estimate of the systemic
      clearance (CL) and inter-compartmental CL was 0.00732 l h(-1) (4.9%) and 0.0224 l
      h(-1) (15.4%). For subcutaneous administration, the absorption rate constant was
      0.012 h(-1) (6.6%) and bioavailability was nearly 100% in healthy and mild to
      moderate asthma patients. Both V and CL increased with body weight. CL (but not
      V) decreased with increasing baseline albumin concentrations. UC patients had an
      increased CL of 72.3% (10.5%), after correction for differences in body weight
      and albumin. Moderate to severe asthma patients had decreased bioavailability
      compared with other populations. CONCLUSIONS: Anrukinzumab's PK behave like a
      typical antibody. UC patients were identified to have a faster CL of anrukinzumab
      than healthy volunteers and asthma patients. This finding suggests a higher dose
      level may be required for this population.

PMID- 25614146
TI  - Camelid nanobodies: killing two birds with one stone.
AB  - In recent years, the use of single-domain camelid immunoglobulins, termed vHHs or
      nanobodies, has seen increasing growth in biotechnology, pharmaceutical
      applications and structure/function research. The usefulness of nanobodies in
      structural biology is now firmly established, as they provide access to new
      epitopes in concave and hinge regions - and stabilize them. These sites are often
      associated with enzyme inhibition or receptor neutralization, and, at the same
      time, provide favorable surfaces for crystal packing. Remarkable results have
      been achieved by using nanobodies with flexible multi-domain proteins, large
      complexes and, last but not least, membrane proteins. While generating nanobodies
      is still a rather long and expensive procedure, the advent of naive libraries
      might be expected to facilitate the whole process. 

PMID- 25614145
TI  - Analysis of the age of Panax ginseng based on telomere length and telomerase
      activity.
AB  - Ginseng, which is the root of Panax ginseng (Araliaceae), has been used in
      Oriental medicine as a stimulant and dietary supplement for more than 7,000
      years. Older ginseng plants are substantially more medically potent, but ginseng
      age can be simulated using unscrupulous cultivation practices. Telomeres
      progressively shorten with each cell division until they reach a critical length,
      at which point cells enter replicative senescence. However, in some cells,
      telomerase maintains telomere length. In this study, to determine whether
      telomere length reflects ginseng age and which tissue is best for such an
      analysis, we examined telomerase activity in the main roots, leaves, stems,
      secondary roots and seeds of ginseng plants of known age. Telomere length in the
      main root (approximately 1 cm below the rhizome) was found to be the best
      indicator of age. Telomeric terminal restriction fragment (TRF) lengths, which
      are indicators of telomere length, were determined for the main roots of plants
      of different ages through Southern hybridization analysis. Telomere length was
      shown to be positively correlated with plant age, and a simple mathematical model
      was formulated to describe the relationship between telomere length and age for
      P. ginseng. 

PMID- 25614147
TI  - Language dysfunction is associated with age of onset of benign epilepsy with
      centrotemporal spikes in children.
AB  - AIMS: To assess the language function of children with benign epilepsy with
      centrotemporal spikes (BECTS), and investigate associated risk factors. METHODS:
      The language function of 63 children with BECTS and 30 healthy controls was
      assessed using the language subtest of the Chinese version of the Wechsler
      Intelligence Scale for Children (C-WISC). Multiple linear regression analysis was
      applied to assess the risk factors of language dysfunction in children with
      BECTS. RESULTS: The total score of language test of C-WISC, and the individual
      scores, were significantly lower in children with BECTS compared with the scores
      attained by the healthy controls, and were also significantly lower in children
      with BECTS with onset earlier than 6 years of age compared with those whose
      disease onset occurred later. There were no significant correlations between
      language function and treatment, frequency of seizures, lateralization of
      centrotemporal spikes, or duration of seizures, but there was a positive
      correlation between language dysfunction and the age at disease onset.
      CONCLUSION: Children with BECTS have language difficulties, especially those with
      earlier disease onset. Early age at seizure onset is a risk factor for language
      dysfunction in children with BECTS.

PMID- 25614148
TI  - Clinical efficacy and tolerability of a novel selective corticosteroid in atopic
      dermatitis--two randomised controlled trials.
AB  - Topical corticosteroids remain the first-line therapy for atopic dermatitis (AD).
      Hence, we investigated the efficacy and safety profile of a novel selective
      corticosteroid, GW870086. We performed 2 randomised, double-blind, controlled
      studies with 25 AD patients and 20 healthy subjects. The changes in the Three
      Item Severity (TIS) score and the skin thickness were the primary end points,
      respectively. The adjusted TIS score (day 22) shows that the novel corticosteroid
      resulted in a non-significant, but dose-dependent reduction compared to placebo
      (GW870086 0.2% vs. placebo = -0.38, GW870086 2% vs. placebo = -0.89). Significant
      skin thinning was observed in the second study on days 14 and 21 when patients
      were treated with the comparator but not with the novel corticosteroid compared
      to placebo. The clinical efficacy of the new selective corticosteroid was not
      superior to placebo, although a dose-dependent improvement upon treatment was
      noticed without the onset of skin thinning.

PMID- 25614149
TI  - V-Y vertebral body osteotomy for the treatment of fixed sagittal plane spinal
      deformity.
AB  - BACKGROUND CONTEXT: Fixed sagittal plane imbalance (FSI) has traditionally been
      corrected by either opening or closing wedge osteotomies or vertebral column
      resections. These methods involve multiple vertebrae and have been associated
      with limited degrees of correction and/or neurovascular compromise. PURPOSE: We
      describe a new V-Y vertebral osteotomy (VYO) that involves a single vertebra,
      allowing for correction of all three columns in a safer fashion. STUDY DESIGN: A
      prospective assessment of the degree of correction pre- and post-VYO in a
      tertiary spinal center. PATIENT SAMPLE: Ten consecutive patients presenting with
      sagittal plane imbalance were enrolled in this study. OUTCOME MEASURES: Outcomes
      were assessed with pre- (preop) and postoperative (postop) outcome questionnaires
      (Oswestry Disability Index [ODI] and Scoliosis Research Society-24) and
      radiography. METHODS: Ten patients underwent VYO at L3 with varying levels of
      instrumentation. The procedure involves a V-shaped osteotomy in the sagittal
      plane, sparing the anterior 50% of the body, the apex of which is then converted
      to a Y shape, and the osteotomy closed. RESULTS: Patients were followed for a
      mean of 36 months (24-48 months). The procedure led to significant improvements
      in sagittal balance, lumbar lordosis, thoracic kyphosis, coronal balance, sacral
      inclination, and pelvic incidence. The average degree of correction achieved was
      44.58 degrees +/-6.19 degrees  (mean+/-standard deviation). The mean blood loss
      was 1,287+/-350 mL and the operative time was 220+/-24 minutes. The mean preop
      ODI was 72% (range 58%-85%) and postop ODI averaged 22% (range 10%-30%). The mean
      preop SRS-24 score was 30.1 and postop was 101. CONCLUSIONS: The VYO provides a
      safe correction of up to 45 degrees  at a single osteotomy site in FSI patients.
      It involves an isolated posterior approach and is recommended for corrections
      below the region of the conus.

PMID- 25614150
TI  - Validation of cone-beam computed tomography and magnetic resonance imaging of the
      porcine spine: a comparative study with multidetector computed tomography and
      anatomical specimens.
AB  - BACKGROUND CONTEXT: New spinal interventions or implants have been tested on ex
      vivo or in vivo porcine spines, as they are readily available and have been
      accepted as a comparable model to human cadaver spines. Imaging-guided
      interventional procedures of the spine are mostly based on fluoroscopy or, still,
      on multidetector computed tomography (MDCT). Cone-beam computed tomography (CBCT)
      and magnetic resonance imaging (MRI) are also available methods to guide
      interventional procedures. Although some MDCT data from porcine spines are
      available in the literature, validation of the measurements on CBCT and MRI is
      lacking. PURPOSE: To describe and compare the anatomical measurements
      accomplished with MDCT, CBCT, and MRI of lumbar porcine spines to determine if
      CBCT and MRI are also useful methods for experimental studies. STUDY DESIGN: An
      experimental descriptive-comparative study. METHODS: Sixteen anatomical
      measurements of an individual vertebra from six lumbar porcine spines (n=36
      vertebrae) were compared with their MDCT, CBCT, and MRI equivalents. Comparisons
      were made for the absolute values of the parameters. RESULTS: Similarities were
      found in all imaging methods. Significant correlation (p<.05) was observed with
      all variables except those that included cartilaginous tissue from the end plates
      when the anatomical study was compared with the imaging methods. CONCLUSIONS: The
      CBCT and MRI provided imaging measurements of the lumbar porcine spines that were
      similar to the anatomical and MDCT data, and they can be useful for specific
      experimental research studies.

PMID- 25614151
TI  - Percutaneous laser disc decompression versus conventional microdiscectomy in
      sciatica: a randomized controlled trial.
AB  - BACKGROUND CONTEXT: Percutaneous laser disc decompression (PLDD) is a minimally
      invasive treatment for lumbar disc herniation, with Food and Drug Administration
      approval since 1991. However, no randomized trial comparing PLDD to conventional
      treatment has been performed. PURPOSE: In this trial, we assessed the
      effectiveness of a strategy of PLDD as compared with conventional surgery. STUDY
      DESIGN/SETTING: This randomized prospective trial with a noninferiority design
      was carried out in two academic and six teaching hospitals in the Netherlands
      according to an intent-to-treat protocol with full institutional review board
      approval. PATIENT SAMPLE: One hundred fifteen eligible surgical candidates, with
      sciatica from a disc herniation smaller than one-third of the spinal canal, were
      included. OUTCOME MEASURES: The main outcome measures for this trial were the
      Roland-Morris Disability Questionnaire for sciatica, visual analog scores for
      back and leg pain, and the patient's report of perceived recovery. METHODS:
      Patients were randomly allocated to PLDD (n=57) or conventional surgery (n=58).
      Blinding was impossible because of the nature of the interventions. This study
      was funded by the Healthcare Insurance Board of the Netherlands. RESULTS: The
      primary outcome, Roland-Morris Disability Questionnaire, showed noninferiority of
      PLDD at 8 (-0.1; [95% confidence interval (CI), -2.3 to 2.1]) and 52 weeks (-1.1;
      95% CI, -3.4 to 1.1) compared with conventional surgery. There was, however, a
      higher speed of recovery in favor of conventional surgery (hazard ratio, 0.64
      [95% CI, 0.42-0.97]). The number of reoperations was significantly less in the
      conventional surgery group (38% vs. 16%). Overall, a strategy of PLDD, with
      delayed surgery if needed, resulted in noninferior outcomes at 1 year.
      CONCLUSIONS: At 1 year, a strategy of PLDD, followed by surgery if needed,
      resulted in noninferior outcomes compared with surgery.

PMID- 25614152
TI  - A critical appraisal of the North American Spine Society guidelines with the
      Appraisal of Guidelines for Research and Evaluation II instrument.
AB  - BACKGROUND CONTEXT: The North American Spine Society (NASS) publishes clinical
      guidelines that are taken into consideration worldwide by clinicians who have a
      special interest in spinal surgery. The Appraisal of Guidelines for Research and
      Evaluation (AGREE) II is the second version of the original AGREE instrument to
      assess the quality of guidelines in terms of development process. This appraisal
      aims to evaluate each individual NASS guideline using AGREE II tool to
      demonstrate its methodologic robust and weakness. PURPOSE: To evaluate the
      quality of the clinical practice guidelines published by the NASS. STUDY DESIGN:
      Four appraisers used the AGREE II guideline evaluation instrument to evaluate the
      NASS guidelines. METHODS: All six guidelines available on the NASS web site as of
      July 1, 2014 were evaluated. Four reviewers independently assessed these
      guidelines using the AGREE II instrument. The instrument standardizes the
      quantitative assessment of quality for a guideline's development process across
      six domains that include: scope and purpose, stakeholder involvement, rigor of
      development, clarity and presentation, applicability, and editorial independence.
      Additionally, each reviewer rated the overall quality of the guidelines. RESULTS:
      Overall results for the AGREE II domains across all six guidelines were: scope
      and purpose (median score, 94.4%), stakeholder involvement (median score, 56.9%),
      rigor of development (median score, 91.7%), clarity of presentation (median
      score, 94.4%), applicability (median score, 60.9%), and editorial independence
      (median score, 71.9%). CONCLUSIONS: Our study showed that the quality of the NASS
      guidelines needs some improvement. There is a critical need for broader
      stakeholder involvement including patient representatives and health economists.
      Consideration of resource implications and monitoring process and standardization
      of how recommendations are implemented need to be improved. Studies analyzing
      facilitators and barriers would be helpful for future NASS guidelines.

PMID- 25614153
TI  - Hyperthyroidism in pregnancy.
AB  - INTRODUCTION: Hyperthyroidism is characterised by high levels of serum thyroxine
      and triiodothyronine, and low levels of thyroid-stimulating hormone. The main
      causes of hyperthyroidism in pregnancy are Graves' disease and chorionic
      gonadotrophin (hCG)-mediated hyperthyroidism. METHODS AND OUTCOMES: We conducted
      a systematic review and aimed to answer the following clinical question: What are
      the effects of antithyroid drug treatments for hyperthyroidism in pregnancy? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to June 2014 (Clinical Evidence reviews are updated periodically; please check
      our website for the most up-to-date version of this review). We included harms
      alerts from relevant organisations such as the US Food and Drug Administration
      (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
      RESULTS: We found no studies that met our inclusion criteria. We performed a
      GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In
      this systematic review we present information relating to the effectiveness and
      safety of the following interventions: antithyroid drugs (carbimazole/thiamazole
      and propylthiouracil).

PMID- 25614154
TI  - Steady, dynamic, creep/recovery, and textural properties of yoghurt/molasses
      blends: Temperature sweep tests and applicability of Cox-Merz rule.
AB  - In this study, physicochemical, rheological (steady, dynamic, and
      creep/recovery), and textural properties of yoghurt/molasses blends (0, 5, 10,
      and 15% molasses) were investigated. The blends showed shear thinning behavior,
      as described by Ostwald de Waele model (R(2) ( )>= 0.955). Consistency
      coefficient value (K) of the blends decreased with increasing molasses
      concentration in the sample. Storage modulus (G') of blends was higher than loss
      modulus (G"), exhibiting weak gel-like behavior. Molasses addition decreased G'
      and G" values. Temperature sweep tests indicated that blends followed Arrhenius
      relationship. A modified Cox-Merz rule was applicable using shift factors.
      Compliance values (J(t)) increased as molasses concentration increased, revealing
      that deformation stability and internal viscosity (eta1) decreased with
      concentration. Creep behavior was characterized using Burger model. Obtained J
      data as a function of time could be satisfactorily fitted to Burger model (R(2) (
      )>= 0.994). The final percentage recovery of blends remarkably decreased with the
      increase of molasses concentration. Firmness, consistency, cohesiveness, and
      viscosity index values decreased with molasses addition. According to the results
      of the current study, molasses amount to be added to the yoghurt should be
      determined regarding rheological properties since resistance of the sample to
      deformation decreased with increase in molasses concentration. 

PMID- 25614155
TI  - Comparison of tamsulosin plus serenoa repens with tamsulosin in the treatment of
      benign prostatic hyperplasia in Korean men: 1-year randomized open label study.
AB  - INTRODUCTION: In Korea, increasing attention has recently been given to the use
      of phytotherapeutic agents to alleviate the symptoms of BPH. Serenoa repens has
      been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the
      treatment of BPH in previous studies. The present study was designed to compare
      the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only
      over 12 months in men with LUTS secondary to BPH. MATERIALS AND METHODS: One
      hundred forty men with symptomatic BPH (IPSS>=10) were recruited in our hospital
      for a 12-month, open-label, randomized trial. Patients were randomly assigned to
      either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day (n=60) or tamsulosin
      0.2 mg/day only (n=60). Prostate volume and PSA were measured at baseline and at
      end-point, whereas total IPSS, and its storage and voiding subscores, LUTS
      related QoL, Qmax, and PVR were evaluated at baseline and later every 6 months.
      RESULTS: Total 103 patients were finally available: 50 in the TAM+SR group and 53
      in the TAM group. At 12 months, total IPSS decreased by 5.8 with TAM+SR and 5.5
      with TAM (p=0.693); the storage symptoms improved significantly more with TAM+SR
      (-1.7 vs. -0.8 with TAM, p=0.024). This benefit with regard to storage symptom in
      the TAM+SR group lasts at 12 months (-1.9 vs. -0.9, p=0.024). The changes of
      voiding subscore, LUTS-related QoL, Qmax, PVR, PSA, and prostate volume showed no
      significant differences between the TAM+SR and TAM groups. During the treatment
      period, 8 patients (16.9%) with TAM and 10 (20%) with TAM+SR had drug-related
      adverse reactions, which included ejaculatory disorders, postural hypotension,
      dizziness, headache, gastro-intestinal disorders, rhinitis, fatigue and asthenia.
      CONCLUSIONS: The combination treatment of Serenoa repens and tamsulosin was shown
      to be more effective than tamsulosin monotherapy in reducing storage symptoms in
      BPH patients after 6 months and up to 12 months of treatment.

PMID- 25614156
TI  - Physician-assisted death with limited access to palliative care.
AB  - Even among advocates of legalising physician-assisted death, many argue that this
      should be done only once palliative care has become widely available. Meanwhile,
      according to them, physician-assisted death should be banned. Four arguments are
      often presented to support this claim, which we call the argument of lack of
      autonomy, the argument of existing alternatives, the argument of unfair
      inequalities and the argument of the antagonism between physician-assisted death
      and palliative care. We argue that although these arguments provide strong
      reasons to take appropriate measures to guarantee access to good quality
      palliative care to everyone who needs it, they do not justify a ban on physician
      assisted death until we have achieved this goal. 

PMID- 25614157
TI  - Fast and low-cost decentralized surveillance of transmission of tuberculosis
      based on strain-specific PCRs tailored from whole genome sequencing data: a pilot
      study.
AB  - Molecular epidemiology has transformed our knowledge of how tuberculosis (TB) is
      transmitted. Whole genome sequencing (WGS) has reached unprecedented levels of
      accuracy. However, it has increased technical requirements and costs, and
      analysis of data delays results. Our objective was to find a way to reconcile
      speed and ease of implementation with the high resolution of WGS. The targeted
      regional allele-specific oligonucleotide PCR (TRAP) assay presented here is based
      on allele-specific PCR targeting strain-specific single nucleotide polymorphisms,
      identified from WGS, and makes it possible to track actively transmitted
      Mycobacterium tuberculosis strains. A TRAP assay was optimized to track the most
      actively transmitted strains in a population in Almeria, Southeast Spain, with
      high rates of TB. TRAP was transferred to the local laboratory where transmission
      was occurring. It performed well from cultured isolates and directly from sputa,
      enabling new secondary cases of infection from the actively transmitted strains
      to be detected. TRAP constitutes a fast, simple and low-cost tool that could
      modify surveillance of TB transmission. This pilot study could help to define a
      new model to survey TB transmission based on a decentralized multinodal network
      of local laboratories applying fast and low-cost TRAPs, which are developed by
      central reference centres, tailored to the specific demands of transmission at
      each local node. 

PMID- 25614158
TI  - Survival of rhinoviruses on human fingers.
AB  - Rhinovirus is the main cause of the common cold, which remains the most frequent
      infection worldwide among humans. Knowledge and understanding of the rhinovirus
      transmission route is important to reduce morbidity as only preventive measures
      are effective. In this study, we investigated the potential of rhinovirus to
      survive on fingers. Rhinovirus-B14 was deposited on fingers for 30, 60, 90 and
      120 min. Survival was defined as the ability of the virus to grow after 7 days,
      confirmed by immunofluorescence. Rhinovirus survival was not dependent on
      incubation time on fingers. Droplet disruption had no influence on survival.
      Survival was frequent with high rhinovirus concentrations, but rare with low
      concentration droplets, which corresponded to the usual rhinovirus concentrations
      in mucus observed in children and adults, respectively. Our study confirms that
      rhinovirus infectiousness is related to the viral concentration in droplets and
      suggests that children represent the main transmission source, which occurs only
      rarely via adults. It confirms also that rhinovirus hand-related transmission is
      possible and supports hand hygiene as a key prevention measure. 

PMID- 25614159
TI  - Cochrane review summary: smartphone and tablet self-management apps for asthma.

PMID- 25614160
TI  - Diastolic dysfunction and endothelial dysfunction in systemic lupus
      erythematosus.

PMID- 25614161
TI  - Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation.
AB  - Sphingolipids are involved in the pathogenesis of inflammatory diseases. The
      central molecule is ceramide, which can be converted into ceramide-1-phosphate
      (C1P). Although C1P can exert anti- and pro-inflammatory effects, its influence
      on cigarette smoke (CS)-induced lung inflammation is unknown. We aimed to clarify
      the role of C1P in the pathogenesis of CS-triggered pulmonary inflammation and
      emphysema in humans and mice. The effects of C1P were addressed on CS-induced
      lung inflammation in C57BL/6 mice, CS extract-triggered activation of human
      airway epithelial cells (AECs) and neutrophils from patients with chronic
      obstructive pulmonary disease. Differential cell counts in bronchoalveolar lavage
      fluid were determined by flow cytometry and pro-inflammatory cytokines were
      measured by ELISA. Expression and DNA binding of nuclear factor (NF)-kappaB and
      neutral sphingomyelinase (nSMase) were quantified by PCR, electrophoretic
      mobility shift and fluorometric assays. C1P reduced CS-induced acute and chronic
      lung inflammation and development of emphysema in mice, which was associated with
      a reduction in nSMase and NF-kappaB activity in the lungs. nSMase activity in
      human serum correlated negatively with forced expiratory volume in 1 s %
      predicted. In human AECs and neutrophils, C1P inhibited CS-induced activation of
      NF-kappaB and nSMase, and reduced pro-inflammatory cytokine release. Our results
      suggest that C1P is a potential target for anti-inflammatory treatment in CS
      induced lung inflammation. 

PMID- 25614162
TI  - Age-adjusted high-sensitivity troponin T cut-off value for risk stratification of
      pulmonary embolism.
AB  - High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism
      patients at low risk of an adverse outcome. In 682 normotensive pulmonary
      embolism patients we investigate whether an optimised hsTnT cut-off value and
      adjustment for age improve the identification of patients at elevated risk.
      Overall, 25 (3.7%) patients had an adverse 30-day outcome. The established hsTnT
      cut-off value of 14 pg.mL(-1) retained its high prognostic value (OR (95% CI)
      16.64 (2.24-123.74); p=0.006) compared with the cut-off value of 33 pg.mL(-1)
      calculated by receiver operating characteristic analysis (7.14 (2.64-19.26);
      p<0.001). In elderly (aged >=75 years) patients, an age-optimised hsTnT cut-off
      value of 45 pg.mL(-1) but not the established cut-off value of 14 pg.mL(-1)
      predicted an adverse outcome. An age-adjusted hsTnT cut-off value (>=14 pg.mL(-1)
      for patients aged <75 years and >=45 pg.mL(-1) for patients aged >=75 years)
      provided additive and independent prognostic information on top of the simplified
      pulmonary embolism severity index (sPESI) and echocardiography (OR 4.56 (1.30
      16.01); p=0.018, C-index=0.77). A three-step approach based on the sPESI, hsTnT
      and echocardiography identified 16.6% of all patients as being at higher risk
      (12.4% adverse outcome). Risk assessment of normotensive pulmonary embolism
      patients was improved by the introduction of an age-adjusted hsTnT cut-off value.
      A three-step approach helped identify patients at higher risk of an adverse
      outcome who might benefit from advanced therapy.

PMID- 25614163
TI  - Mechanisms of development of multimorbidity in the elderly.
AB  - In ageing populations many patients have multiple diseases characterised by
      acceleration of the normal ageing process. Better understanding of the signalling
      pathways and cellular events involved in ageing shows that these are
      characteristic of many chronic degenerative diseases, such as chronic obstructive
      pulmonary disease (COPD), chronic cardiovascular and metabolic diseases, and
      neurodegeneration. Common mechanisms have now been identified in these diseases,
      which show evidence of cellular senescence with telomere shortening, activation
      of PI3K-AKT-mTOR signalling, impaired autophagy, mitochondrial dysfunction, stem
      cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence
      and low grade chronic inflammation ("inflammaging"). Many of these pathways are
      driven by chronic oxidative stress. There is also a reduction in anti-ageing
      molecules, such as sirtuins and Klotho, which further accelerates the ageing
      process. Understanding these molecular mechanisms has identified several novel
      therapeutic targets and several drugs have already been developed that may slow
      the ageing process, as well as lifestyle interventions, such as diet and physical
      activity. This indicates that in the future new treatment approaches may target
      the common pathways involved in multimorbidity and this area of research should
      be given high priority. Thus, COPD should be considered as a component of
      multimorbidity and common disease pathways, particularly accelerated ageing,
      should be targeted. 

PMID- 25614164
TI  - Riociguat for the treatment of pulmonary arterial hypertension: a long-term
      extension study (PATENT-2).
AB  - Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary
      arterial hypertension. In the 12-week PATENT-1 study, riociguat was well
      tolerated and improved several clinically relevant end-points in patients with
      pulmonary arterial hypertension who were treatment naive or had been pretreated
      with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label
      extension evaluated the long-term safety and efficacy of riociguat. Eligible
      patients from the PATENT-1 study received riociguat individually adjusted up to a
      maximum dose of 2.5 mg three times daily. The primary objective was to assess the
      safety and tolerability of riociguat; exploratory efficacy assessments included 6
      min walking distance and World Health Organization (WHO) functional class.
      Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at
      this interim analysis (March 2013). The safety profile of riociguat in PATENT-2
      was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary
      haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min
      walking distance and WHO functional class observed in PATENT-1 persisted for up
      to 1 year in PATENT-2. In the observed population at the 1-year time point,
      mean+/-sd 6-min walking distance had changed by 51+/-74 m and WHO functional
      class had improved in 33%, stabilised in 61% and worsened in 6% of the patients
      versus the PATENT-1 baseline. Long-term riociguat was well tolerated in patients
      with pulmonary arterial hypertension, and led to sustained improvements in
      exercise capacity and functional capacity for up to 1 year.

PMID- 25614165
TI  - Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor
      prognosis. IPF appears to be heterogeneous in pathobiology with ~40% of IPF
      patients found to have elevated levels of circulating antibodies to the
      autoantigen type V collagen (col(V)). Following a targeted, precision medicine
      approach, we conducted a phase 1 study to test the safety and explore potential
      efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody
      positive IPF patients. We divided 30 antibody-positive IPF patients into three
      cohorts for daily dosing over a 24-week period. All patients completed treatment
      without serious adverse events, acute exacerbations or IPF-related
      hospitalisations. A decline in lung function occurred in the lowest-dose cohort
      that was comparable to that reported in placebo arms of published IPF trials. In
      contrast, the highest-dose cohort showed a trend toward stabilisation of forced
      vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q
      to anti-col(V) antibodies. IW001 may modulate the immune response to col(V) and
      may represent a new therapeutic for col(V)- reactive IPF patients. 

PMID- 25614166
TI  - Airway wall thickness associated with forced expiratory volume in 1 second
      decline and development of airflow limitation.
AB  - Airway wall thickness and emphysema contribute to airflow limitation. We examined
      their association with lung function decline and development of airflow
      limitation in 2021 male smokers with and without airflow limitation. Airway wall
      thickness and emphysema were quantified on chest computed tomography and
      expressed as the square root of wall area of a 10-mm lumen perimeter (Pi10) and
      the 15th percentile method (Perc15), respectively. Baseline and follow-up (median
      (interquartile range) 3 (2.9-3.1) years) spirometry was available. Pi10 and
      Perc15 correlated with baseline forced expiratory volume in 1 s (FEV1) (r= -0.49
      and 0.11, respectively (p<0.001)). Multiple linear regression showed that Pi10
      and Perc15 at baseline were associated with a lower FEV1 after follow-up
      (p<0.05). For each sd increase in Pi10 and decrease in Perc15 the FEV1 decreased
      by 20 mL and 30.2 mL, respectively. The odds ratio for developing airflow
      limitation after 3 years was 2.45 for a 1-mm higher Pi10 and 1.46 for a 10-HU
      lower Perc15 (p<0.001). A greater degree of airway wall thickness and emphysema
      was associated with a higher FEV1 decline and development of airflow limitation
      after 3 years of follow-up.

PMID- 25614167
TI  - Matrix Gla protein limits pulmonary arteriovenous malformations in ALK1
      deficiency.

PMID- 25614168
TI  - Complicated grief after death of a relative in the intensive care unit.
AB  - An increased proportion of deaths occur in the intensive care unit (ICU). We
      performed this prospective study in 41 ICUs to determine the prevalence and
      determinants of complicated grief after death of a loved one in the ICU.
      Relatives of 475 adult patients were followed up. Complicated grief was assessed
      at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25).
      Relatives also completed the Hospital Anxiety and Depression Scale at 3 months,
      and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms
      at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to
      identify determinants of complicated grief after 6 months. Among the 475
      patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief
      symptoms were identified in 147 (52%) relatives. Independent determinants of
      complicated grief symptoms were either not amenable to changes (relative of
      female sex, relative living alone and intensivist board certification before
      2009) or potential targets for improvements (refusal of treatment by the patient,
      patient died while intubated, relatives present at the time of death, relatives
      did not say goodbye to the patient, and poor communication between physicians and
      relatives). End-of-life practices, communication and loneliness in bereaved
      relatives may be amenable to improvements.

PMID- 25614170
TI  - Serious adverse events during a 6-min walk test in patients with pulmonary
      hypertension.

PMID- 25614169
TI  - The tolerability of linezolid in the treatment of nontuberculous mycobacterial
      disease.

PMID- 25614171
TI  - Efficacy of short-term prednisolone treatment in patients with chronic
      eosinophilic pneumonia.
AB  - In patients with chronic eosinophilic pneumonia (CEP), dramatic improvements are
      seen in response to corticosteroid therapy; however, relapse is common after
      treatment has ceased. The optimal duration of corticosteroid therapy remains
      unclear. In a randomised, open-label, parallel group study, eligible patients
      with CEP received oral prednisolone for either 3 months (3-month group) or 6
      months (6-month group), followed by 2 years observation. All patients were
      treated with an initial dose of prednisolone of 0.5 mg.kg(-1).day(-1), which was
      then tapered and discontinued at either 3 or 6 months. The primary end-point was
      relapse during the follow-up period. In the final analysis, there were 23
      patients in the 3-month group and 21 patients in the 6-month group. All patients
      showed a good response to prednisolone treatment. There were 12 (52.1%) relapses
      in the 3-month group and 13 (61.9%) relapses in the 6-month group. No significant
      difference was found in the cumulative rate of relapse (p=0.56). All relapse
      cases showed improvement upon resumption of prednisolone treatment. No difference
      was observed in the rate of relapse between the 3- and 6-month prednisolone
      treatment groups for patients with CEP. 

PMID- 25614172
TI  - Unified baseline and longitudinal mortality prediction in idiopathic pulmonary
      fibrosis.
AB  - The Gender-Age-Physiology (GAP) model is a validated, baseline-risk prediction
      model for mortality in idiopathic pulmonary fibrosis. Longitudinal variables have
      been shown to contribute to risk prediction in idiopathic pulmonary fibrosis and
      may improve the predictive performance of the baseline GAP model. Our aims were
      to further validate the GAP model and evaluate whether the addition of
      longitudinal variables improves its predictive performance. The study population
      was derived from a large clinical trials cohort of patients with idiopathic
      pulmonary fibrosis (n=1109). Model performance was determined by improvement in
      the C-statistic, net reclassification improvement, clinical net reclassification
      improvement, and a goodness-of-fit test. The GAP model had good discriminative
      performance with a C-statistic of 0.757 (95% CI 0.750-0.764). However, the
      original GAP model tended to overestimate risk in this cohort. A novel, easy to
      use model, consisting of the original GAP predictors plus history of respiratory
      hospitalisation and 24-week change in forced vital capacity (the longitudinal GAP
      model) improved model performance with a C-statistic of 0.785 (95% CI 0.780
      0.790), net reclassification improvement of 8.5%, clinical net reclassification
      improvement of 25%, and a goodness-of-fit test of 0.929. The Longitudinal GAP
      model, along with the original GAP model, may unify baseline and longitudinal
      mortality risk prediction in idiopathic pulmonary fibrosis. 

PMID- 25614173
TI  - Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia:
      risk and prognosis.
AB  - The sensitivity of blood cultures in the diagnosis of bacteraemia for community
      acquired pneumonia is low. Recommendations, by guidelines, to perform blood
      cultures are discordant. We aimed to determine the incidence, microbial
      aetiology, risk factors and outcomes of bacteraemic patients with community
      acquired pneumonia, including cases with antibiotic-resistant pathogens (ARP). A
      prospective, observational study was undertaken on consecutive adult patients
      admitted to the Hospital Clinic of Barcelona (Barcelona, Spain) with community
      acquired pneumonia and blood cultures were obtained. Of the 2892 patients
      included, bacteraemia was present in 297 (10%) patients; 30 (10%) of whom had ARP
      (multidrug-resistant Streptococcus pneumoniae, methicillin-resistant
      Staphylococcus aureus, Pseudomonas aeruginosa, and an extended spectrum of beta
      lactamase producing Enterobacteriaceae). In multivariate analyses, pleuritic
      pain, C-reactive protein >=21.6 mg.dL(-1) and intensive care unit admissions were
      independently associated with bacteraemia, while prior antibiotic treatment and
      pneumococcal vaccine were protective factors. The risk factors for ARP
      bacteraemia were previous antibiotics and C-reactive protein <22.2 mg.dL(-1),
      while pleuritic pain was the only protective factor in the multivariate analysis.
      Bacteraemia (excluding ARP), appropriate empiric treatment, neurological disease,
      arterial oxygen tension/inspiratory oxygen fraction <250, pneumonia severity
      index risk classes IV and V, and intensive care unit admission were independently
      associated with a 30-day hospital mortality in the multivariate analysis.
      Inappropriate therapy was more frequent in ARP bacteraemia, compared with other
      bacteraemias (27% versus 3%, respectively, p<0.001). Antibiotic therapy protected
      against bacteraemia, but increased specifically the risk of bacteraemia from ARP
      due to the inappropriate coverage of these pathogens. Identifying patients at
      risk of ARP bacteraemia would help in deciding appropriate empiric antimicrobial
      therapy. The results from this study provide evidence concerning community
      acquired pneumonia patients in whom blood cultures should not be performed. 

PMID- 25614174
TI  - Pulmonary manifestations in adult patients with chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by
      failure of superoxide production in phagocytic cells. The disease is
      characterised by recurrent infections and inflammatory events, frequently
      affecting the lungs. Improvement of life expectancy now allows most patients to
      reach adulthood. We aimed to describe the pattern of pulmonary manifestations
      occurring during adulthood in CGD patients. This was a retrospective study of the
      French national cohort of adult patients (>=16 years old) with CGD. Medical data
      were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds
      of adult patients. Their incidence was significantly higher than in childhood
      (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite
      anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per
      year per patient) and asymptomatic in 37% of the cases. They often required lung
      biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned
      28% of adult patients, frequently associated with a concomitant fungal infection
      (40%). They were more frequent in patients with the X-linked form of CGD. Immune
      modulator therapies were required in most cases (70%). Respiratory manifestations
      are major complications of CGD in adulthood. Noninfectious pulmonary
      manifestations are as deleterious as infectious pneumonia. A specific respiratory
      monitoring is necessary. 

PMID- 25614176
TI  - Using urinary biomarkers to evaluate polycyclic aromatic hydrocarbon exposure in
      126 preschool children in Ohio.
AB  - Limited data exist on exposures of young children to polycyclic aromatic
      hydrocarbons (PAHs) in the United States (US). The urinary metabolite of pyrene,
      1-hydroxypyrene (1-OHPyr), is widely used as a biomarker of total PAH exposure.
      Our objectives were to quantify urinary 1-OHPyr levels in 126 preschool children
      over a 48-h period and to examine associations between selected
      sociodemographic/lifestyle factors and urinary 1-OHPyr levels. Monitoring was
      performed at 126 homes and 16 daycares in Ohio in 2001, and questionnaires and
      urine samples were collected. The median urinary 1-OHPyr level was 0.33 ng/mL. In
      a multiple regression model, sampling season (p = 0.0001) and natural log (ln)
      transformed creatinine concentration (p = 0.0006) were highly significant
      predictors of ln-transformed 1-OH-Pyr concentration; cooking appliance type (p =
      0.096) was a marginally significant predictor of ln(1-OHPyr). These children had
      higher median urinary 1-OHPyr levels compared to other US children (<= 0.15
      ng/mL) in previously published studies, which suggests possible geographical
      differences in PAH exposure. 

PMID- 25614175
TI  - Plasma pro-surfactant protein B and lung function decline in smokers.
AB  - Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to
      predict the development of lung cancer in current and ex-smokers, but the ability
      of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD)
      severity is unknown. We evaluated the performance characteristics of pro-SFTPB as
      a biomarker of lung function decline in a population of current and ex-smokers.
      Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in
      the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was
      performed to determine the relationship of pro-SFTPB levels to changes in forced
      expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1
      and the burden of emphysema observed in computed tomography (CT) scans. Plasma
      pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and
      FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the
      burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were
      also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2
      years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with
      increased severity of airflow limitation and accelerated decline in lung
      function. Pro-SFTPB is a promising biomarker for COPD severity and progression.

PMID- 25614177
TI  - Secondary hyperparathyroidism and its relationship with sarcopenia in elderly
      women.
AB  - Low dietary intake of calcium and poor vitamin D status during aging can result
      in mild secondary hyperparathyroidism, which may be associated with low muscle
      mass and reduced strength in the elderly. The aim of this study was to
      investigate whether low vitamin D, high parathormone (PTH), or both, are
      associated with sarcopenia. A total of 105 women, 35 with sarcopenia and 70
      without sarcopenia, were enrolled in the present study. Body composition
      measurements were performed by DXA and sarcopenia was defined as skeletal muscle
      mass index<5.45 kg/m2 and grip strength lower than 20 kg. Three-day dietary
      records were taken and adjustments for energy intake made. The estimated average
      requirement (EAR) method was adopted as a cut-off point for estimating the
      prevalence of inadequate intake. Serum total calcium, phosphorus, creatinine,
      intact PTH, and 25(OH)D were measured. Only 1% of the patients met the daily
      adequate intake for vitamin D and 11% met the daily adequate intake for calcium.
      Notably, the prevalence of sarcopenia was higher in hyperparathyroidism
      (25(OH)D<20 ng/mL and PTH>65 pg/dL) than in the absence of hyperparathyroidism
      (41.2 vs 16.2%, respectively; p=0.046). The odds ratio for sarcopenia in
      hyperparathyroidism cases was 6.81 (95%CI 1.29-35.9) compared with participants
      who had low PTH and a high 25(OH)D concentration. The present study showed that
      vitamin D insufficiency associated with secondary hyperparathyroidism increased
      the risk of sarcopenia, suggesting that the suppression of hyperparathyroidism by
      ensuring adequate calcium and vitamin D intake should be considered in
      interventional studies to confirm potential benefits.

PMID- 25614178
TI  - Gait characteristics associated with walking speed decline in older adults:
      results from the Baltimore Longitudinal Study of Aging.
AB  - BACKGROUND: Understanding the mechanisms that contribute to walking speed decline
      can provide needed insight for developing targeted interventions to reduce the
      rate and likelihood of decline. OBJECTIVE: Examine the association between gait
      characteristics and walking speed decline in older adults. METHODS: Participants
      in the Baltimore Longitudinal Study of Aging aged 60 to 89 were evaluated in the
      gait laboratory which used a three dimensional motion capture system and force
      platforms to assess cadence, stride length, stride width, percent of gait cycle
      in double stance, anterior-posterior mechanical work expenditure (MWE), and
      medial-lateral MWE. Usual walking speed was assessed over 6 m at baseline and
      follow-up. Gait characteristics associated with meaningful decline (decline>=0.05
      m/s/y) in walking speed were evaluated by logistic regression adjusted for age,
      sex, race, height, weight, initial walking speed and follow-up time. RESULTS:
      Among 362 participants, the average age was 72.4 (SD=8.1) years, 51% were female,
      27% were black and 23% were identified has having meaningful decline in usual
      walking speed with an average follow-up time of 3.2 (1.1) years. In the fully
      adjusted model, faster cadence [ORadj=0.65, 95% CI (0.43,0.97)] and longer
      strides [ORadj=0.87, 95% CI (0.83,0.91)] were associated with lower odds of
      decline. However age [ORadj=1.04, 95% CI (0.99,1.10)] was not associated with
      decline when controlling for gait characteristics and other demographics.
      CONCLUSION: A sizable proportion of healthy older adults experienced walking
      speed decline over an average of 3 years. Longer stride and faster cadence were
      protective against meaningful decline in usual walking speed.

PMID- 25614179
TI  - Surgically implanted and non-invasive vagus nerve stimulation: a review of
      efficacy, safety and tolerability.
AB  - Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression
      and is being investigated in heart failure, headache, gastric motility disorders
      and asthma. The first VNS device required surgical implantation of electrodes and
      a stimulator. Adverse events (AEs) are generally associated with implantation or
      continuous on-off stimulation. Infection is the most serious implantation
      associated AE. Bradycardia and asystole have also been described during
      implantation, as has vocal cord paresis, which can last up to 6 months and
      depends on surgical skill and experience. The most frequent stimulation
      associated AEs include voice alteration, paresthesia, cough, headache, dyspnea,
      pharyngitis and pain, which may require a decrease in stimulation strength or
      intermittent or permanent device deactivation. Newer non-invasive VNS delivery
      systems do not require surgery and permit patient-administered stimulation on
      demand. These non-invasive VNS systems improve the safety and tolerability of
      VNS, making it more accessible and facilitating further investigations across a
      wider range of uses.

PMID- 25614180
TI  - Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians.
AB  - Planarians are rapidly developing into very useful research subjects in
      pharmacology and neuroscience research. Here we report that curare, a cholinergic
      nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure
      like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and
      curare (1 mM), while curare alone does not induce significant pSLMs. The simplest
      interpretation of our data is that there are nicotine induced behaviors
      insensitive to curare in our experimental organism. To the best of our knowledge,
      this is the first report on curare-insensitive, nicotine-induced effects in any
      organism.

PMID- 25614182
TI  - Chronic kidney disease in disadvantaged populations.

PMID- 25614181
TI  - Diabetes-induced impairments of the exocytosis process and the effect of
      gabapentin: the link with cholesterol level in neuronal plasma membranes.
AB  - Diabetic neuropathy represents one of the most prevalent complications of
      diabetes mellitus. The aim of this study was to investigate the effect of
      diabetes-induced disturbances in neurons on the Ca(2+)-triggered membrane fusion
      process in cell-free system in relation to plasmalemma cholesterol level. The
      gabapentin therapy on the exocytosis process was also studied. The diabetes in
      rats was induced by streptozotocin (60 mg/kg of body weight, i.p.). After 4 weeks
      of diabetes induction the one group of diabetic rats was treated with gabapentin
      (50 mg/kg, i.p.) during 1 month. Fusion experiments were performed in the cell
      free model system using fluorescent dye octadecylrhodamine B. The [2
      (14)C]serotonin preloaded synaptosomes were used for assay of stimulated
      neurotransmitter release. The synaptosomal plasma membrane cholesterol level in
      diabetic rats was on 12 % higher than in control and was decreased on 5 % after
      gabapentin therapy. The rate of synaptic vesicles fusion with plasma membranes in
      the presence of Ca(2+) and synaptosomal cytosolic proteins was decreased to 14.5
      % in diabetic rats as compared to control (23 %) and after gabapentin
      administration to diabetic rats was raised to 18 %. At diabetes the stimulated
      synaptosomal serotonin release was increased in 1.7-2 folds and was partially
      normalized by gabapentin therapy. Together, these findings suggest that elevated
      cholesterol content in neuronal plasma membranes at diabetes impairs the membrane
      fusion process in neurons that can induce the development of neuropathy. Diabetes
      evoked impairments of the exocytotic process can be attenuated by gabapentin
      therapy.

PMID- 25614184
TI  - The ankle-brachial index is related to left ventricular ejection fraction in
      bonnet macaques.
AB  - Low ankle-brachial index (ABI) is a marker of peripheral arterial disease
      associated with higher cardiovascular risk. ABI has been found to be influenced
      by left ventricular ejection fraction (LVEF), but this relation is confounded by
      atherosclerosis. OBJECTIVES: Since nonhuman primates have a low incidence of
      atherosclerosis, we sought to evaluate the effect of LVEF on ABI in 24 healthy
      female bonnet macaques (age 83 +/- 21 months). METHODS: LVEF was determined by
      echocardiography during anesthesia with ketamine. ABI was determined using
      automatic blood pressure cuff. RESULTS: Mean LVEF was 73 +/- 6%. Mean ABI was
      1.03 (range 0.78-1.17) with similar right and left lower limb values (p = 0.78).
      On univariate analysis, mean ABI was significantly correlated with LVEF (r =
      0.58, p = 0.003) but not with age, crown-rump length or weight. Mean LVEF
      increased in a stepwise manner from lowest to highest ABI tertile (68 +/- 6 vs.
      73 +/- 4 vs. 77 +/- 5%, p = 0.008). On ordinal regression and forced multivariate
      linear analyses, ABI status was independently related to LVEF. CONCLUSIONS: ABI
      is influenced by left ventricular systolic function but not age, height, weight
      or mass index in bonnet macaques. Left ventricular systolic function should be
      accounted for when considering ABI measurements.

PMID- 25614183
TI  - Investigating Hydrophilic Pores in Model Lipid Bilayers Using Molecular
      Simulations: Correlating Bilayer Properties with Pore-Formation Thermodynamics.
AB  - Cell-penetrating and antimicrobial peptides show a remarkable ability to
      translocate across physiological membranes. Along with factors such as electric
      potential-induced perturbations of membrane structure and surface tension
      effects, experiments invoke porelike membrane configurations during the solute
      transfer process into vesicles and cells. The initiation and formation of pores
      are associated with a nontrivial free-energy cost, thus necessitating a
      consideration of the factors associated with pore formation and the attendant
      free energies. Because of experimental and modeling challenges related to the
      long time scales of the translocation process, we use umbrella sampling molecular
      dynamics simulations with a lipid-density-based order parameter to investigate
      membrane-pore-formation free energy employing Martini coarse-grained models. We
      investigate structure and thermodynamic features of the pore in 18 lipids
      spanning a range of headgroups, charge states, acyl chain lengths, and
      saturation. We probe the dependence of pore-formation barriers on the area per
      lipid, lipid bilayer thickness, and membrane bending rigidities in three
      different lipid classes. The pore-formation free energy in pure bilayers and
      peptide translocating scenarios are significantly coupled with bilayer thickness.
      Thicker bilayers require more reversible work to create pores. The pore-formation
      free energy is higher in peptide-lipid systems than in peptide-free lipid systems
      due to penalties to maintain the solvation of charged hydrophilic solutes within
      the membrane environment. 

PMID- 25614185
TI  - Anaplastic thyroid carcinoma with rhabdoid features.
AB  - Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive neoplasm,
      characterized by complete or partial composition by undifferentiated cells. We
      report a case of ATC with rhabdoid features in a 68-year-old male, who presented
      with a rapidly enlarging neck mass. Fine-needle aspiration (FNA) of the thyroid
      mass showed discohesive, pleomorphic round to polygonal rhabdoid cells with one
      to multiple eccentric, large, rounded nuclei with a prominent nucleolus, moderate
      to abundant, globoid cytoplasm which oftentimes harbor a pale para-nuclear
      inclusion. The cytoplasm of some cells contained variously sized, eosinophilic
      granules. Rare cells contained neutrophils in their cytoplasm. Mitoses including
      atypical mitotic figures and necrosis were readily seen. Histologic examination
      of needle core biopsy (NCB) revealed individual dispersed and sheets of
      pleomorphic neoplastic cells with similar cytomorphologic features as described
      above. The tumor extensively infiltrated a myxocollagenous stroma containing
      lymphocytes and neutrophils, and demonstrated foci of necrosis. Tumor cells were
      immunoreactive for keratins AE1/AE3, CAM5.2, and CK19; PAX-8, and p63, but
      negative for S-100, HMB-45, calcitonin, TTF-1, thyroglobulin, CD56, HBME-1,
      glypican-3, PAX-5, myogenin, CD31, and INI-1. The differential diagnosis of this
      malignant rhabdoid tumor is discussed.

PMID- 25614186
TI  - Exposure to Delta9-Tetrahydrocannabinol Impairs the Differentiation of Human
      Monocyte-derived Dendritic Cells and their Capacity for T cell Activation.
AB  - The capacity for human monocytes to differentiate into antigen-presenting
      dendritic cells (DC) can be influenced by a number of immune modulating signals.
      Monocytes express intracellular cannabinoid type 1 (CB1) and 2 (CB2) receptors
      and we demonstrate that exposure to Delta9-tetrahydrocannabinol (THC) inhibits
      the forskolin-induced generation of cyclic adenosine monophosphate in a CB2
      specific manner. In order to examine the potential impact of cannabinoids on the
      generation of monocyte-derived DC, monocytes were cultured in vitro with
      differentiation medium alone [containing granulocyte/macrophage-colony
      stimulating factor (GM-CSF) and Interleukin-4 (IL-4)] or in combination with THC.
      The presence of THC (0.25-1.0 MUg/ml) altered key features of DC differentiation,
      producing a concentration-dependent decrease in surface expression of CD11c, HLA
      DR and costimulatory molecules (CD40 and CD86), less effective antigen uptake,
      and signs of functional skewing with decreased production of IL-12 but normal
      levels of IL-10. When examined in a mixed leukocyte reaction, DC that had been
      generated in the presence of THC were poor T cell activators as evidenced by
      their inability to generate effector/memory T cells or to stimulate robust IFN
      gamma responses. Some of these effects were partially restored by exposure to
      exogenous IL-7 and bacterial superantigen (S. aureus Cowans strain). These
      studies demonstrate that human monocytes express functional cannabinoid receptors
      and suggest that exposure to THC can alter their differentiation into functional
      antigen presenting cells; an effect that may be counter-balanced by the presence
      of other immunoregulatory factors. The impact of cannabinoids on adaptive immune
      responses in individuals with frequent drug exposure remains to be determined. 

PMID- 25614188
TI  - Determination of synthetic phenolic antioxidants and relative metabolites in
      sewage treatment plant and recipient river by high performance liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - Robust analytical methods were developed for the determination of eight emerging
      synthetic phenolic antioxidants (SPAs) and three metabolites in sewage sludge,
      effluent and river water matrices. Accelerated solvent extraction was employed
      for the extraction of the target analytes from sludge, dichloromethane/hexane=3:1
      (extraction solvent) and 90 degrees C (extraction temperature) were used after
      optimization. Silica gel packed column was chosen for the subsequent clean-up
      procedure for sludge extract. For the water sample analysis, liquid-liquid
      extraction combined with silica gel clean-up was used. The targets were
      determined by optimized high performance liquid chromatography-tandem mass
      spectrometry method in negative electrospray ionization mode. The method
      quantification limits of the 11 analytes ranged from 0.1 to 23 ng/L, 0.1 to 20
      ng/L and 0.1 to 15 ng/g for sewage effluent, river water and sludge matrices,
      respectively. The total recoveries of the pretreatment varied from 63 to 106%,
      with relative standard deviations less than 17% for the three matrices at
      different spiking levels. Nine targets including 2,6-di-tert-butyl-4-methylphenol
      (BHT), 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-1,4
      benzoquinone (BHT-Q), 2,6-di-tert-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone
      (BHT-quinol), 3-tert-butyl-4-hydroxyanisole (BHA), 4-tert-octylphenol (4-tOP),
      2,2'-methylenebis(6-tert-butyl-4-methylphenol) (AO 2246), 4,4'-butylidenebis(2
      (1,1-dimethylethyl)-5-methyl-phenol) (AO 44B25) and 1,3,5-trimethyl-2,4,6
      tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene (AO 330) were identified in the
      collected samples, with concentrations ranging 1.1-2325 ng/g and 0.4-2510 ng/L
      for sludge and water matrices, respectively. Sewage effluent was considered as a
      possible contamination source of certain SPA homologues and relative metabolites
      to the recipient aquatic systems.

PMID- 25614187
TI  - Cyclopenta[b]naphthalene cyanoacrylate dyes: synthesis and evaluation as
      fluorescent molecular rotors.
AB  - We describe the design, synthesis and fluorescent profile of a family of
      environment-sensitive dyes in which a dimethylamino (donor) group is conjugated
      to a cyanoacrylate (acceptor) unit via a cyclopenta[b]naphthalene ring system.
      This assembly satisfies the typical D-pi-A motif of a fluorescent molecular rotor
      and exhibits solvatochromic and viscosity-sensitive fluorescence emission. The
      central naphthalene ring system of these dyes was synthesized via a novel
      intramolecular dehydrogenative dehydro-Diels-Alder (IDDDA) reaction that permits
      incorporation of the donor and acceptor groups in variable positions around the
      aromatic core. A bathochromic shift of excitation and emission peaks was observed
      with increasing solvent polarity but the dyes exhibited a complex emission
      pattern with a second red emission band when dissolved in nonpolar solvents.
      Consistent with other known molecular rotors, the emission intensity increased
      with increasing viscosity. Interestingly, closer spatial proximity between the
      donor and the acceptor groups led to decreased viscosity sensitivity combined
      with an increased quantum yield. This observation indicates that structural
      hindrance of intramolecular rotation dominates when the donor and acceptor groups
      are in close proximity. The examined compounds give insight into how excited
      state intramolecular rotation can be influenced by both the solvent and the
      chemical structure. 

PMID- 25614189
TI  - Ultra-high-performance liquid chromatography electrospray ionization tandem mass
      spectrometry for accurate analysis of glycerophospholipids and sphingolipids in
      drug resistance tumor cells.
AB  - Glycerophospholipids and sphingolipids are important signaling molecules which
      are involved in many physiological and pathological processes. Here we reported
      an effective method for accurate analysis of these lipids by liquid
      chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
      The methanol method was adopted for extraction of lipids due to its simplicity
      and high efficiency. It was found that two subclasses of sphingolipids, sulfatide
      (ST) and cerebroside (CB), were heat labile, so a decreased temperature in the
      ion source of MS might be necessary for these compounds analysis. In addition, it
      was found that the isobaric interferences were commonly existent, for example,
      the m/z of 16:0/18:1 PC containing two (13)C isotope being identical to that of
      16:0/18:0 PC determined by a unit mass resolution mass spectrometer; therefore, a
      baseline separation of interferential species was required to maintain
      selectivity and accuracy of analysis. In this work, an ultra-high-performance
      liquid chromatography (UHPLC)-based method was developed for separation of
      interferential species. Moreover, in order to deal with the characteristics of
      different polarity and wide dynamic range of glycerophospholipids and
      sphingolipids in biological systems, three detecting conditions were combined
      together for comprehensive and rational analysis of glycerophospholipids and
      sphingolipids. The method was utilized to profile glycerophospholipids and
      sphingolipids in drug resistant tumor cells. Our results showed that many lipids
      were significantly changed in drug resistant tumor cells compared to paired drug
      sensitive tumor cells. This is a systematic report about the isobaric
      interferences and heat labile compounds interferences when analyzing
      glycerophospholipids and sphingolipids by ESI-MS/MS, which aids in ruling out one
      potential source of systematic error to ensure the accuracy of analysis. 

PMID- 25614190
TI  - Isolation of aspalathin and nothofagin from rooibos (Aspalathus linearis) using
      high-performance countercurrent chromatography: sample loading and compound
      stability considerations.
AB  - Aspalathin and nothofagin, the major dihydrochalcones in rooibos (Aspalathus
      linearis), are valuable bioactive compounds, but their bioactivity has not been
      fully elucidated. Isolation of these compounds using high-performance
      countercurrent chromatography (HPCCC), a gentle, support-free, up-scalable
      technique, offers an alternative to synthesis for obtaining sufficient amounts.
      An HPLC-DAD method was adapted to allow rapid (16 min from injection to
      injection) quantification of the four major compounds (aspalathin, nothofagin,
      isoorientin, orientin) during development of the isolation protocol. The
      traditional shake-flask method, used to determine distribution constants (K(D))
      for target compounds, was also adapted to obtain higher repeatability. Green
      rooibos leaves with a high aspalathin and nothofagin content were selected as
      source material. Sample loading of the polyphenol-enriched extract was limited
      due to constituents with emulsifying properties, but could be increased by
      removing ethanol-insoluble matter. Furthermore, problems with degradation of
      aspalathin during HPCCC separation and further processing could be limited by
      acidifying the HPCCC solvent system. Aspalathin was shown to be fairly stable at
      pH 3 (91% remaining after 29 h) compared to pH 7 (45% remaining after 29 h).
      Aspalathin and nothofagin with high purities (99% and 100%, respectively) were
      obtained from HPCCC fractions after semi-preparative HPLC.

PMID- 25614191
TI  - Enantiomers separation by nano-liquid chromatography: use of a novel sub-2 MUm
      vancomycin silica hydride stationary phase.
AB  - A novel sub-2 MUm chiral stationary phase (CSP) was prepared immobilizing
      vancomycin onto 1.8 MUm diol hydride-based silica particles. The CSP was packed
      into fused silica capillaries of 75 MUm i.d. with a length of 11 cm and evaluated
      by means of nano-liquid chromatography (nano-LC) using model compounds of both
      pharmaceutical and environmental interest (some non-steroidal anti-inflammatory
      drugs, beta-blockers and herbicides). The study of the effect of the linear
      velocity of the mobile phase on chromatographic efficiency showed good
      enantioresolutions up to a value of 5.11 at the optimal linear velocity with
      efficiencies in terms of number of plates per meter in the range 51,650-68,330.
      The results were compared with the ones obtained employing 5 MUm vancomycin
      modified diol-silica particles packed in capillaries of the same i.d. For the
      acidic analytes the sub-2 MUm CSP showed better performances, the baseline chiral
      separation of several studied compounds occurred in an analysis time of less than
      3 min. Column-to-column packing reproducibility (n=3) expressed as relative
      standard deviation was in the range 2.2-5.8% and 0.5-7.7% for retention times and
      peak areas, respectively.

PMID- 25614192
TI  - 'Click' preparation of a novel 'native-phenylcarbamoylated' bilayer cyclodextrin
      stationary phase for enhanced chiral differentiation.
AB  - This paper reports an effective approach for the fabrication of a novel hybrid
      bilayer cyclodextrin (CD) chiral stationary phase (CSP), where native and
      perphenylcarbamoylated-beta-CD were successively immobilized onto silica surface
      via a two-step click approach to form a bilayer CD structure. By decorating the
      bulky phenylcarbamoylated CD onto the unmodified CD silica, the CSP can provide
      multiple interaction sites such as H-bonding (-OH, C=O, -NH-), steric effects, pi
      pi, dipole-dipole and inclusion complexation interactions, which help to broaden
      the CSP's enantioselectivity profile and enhance the enantioselectivity to some
      specific analytes. A group of enantiomer pairs such as isoxazolines,
      bendroflumethiazide, indoprofen, diperodon, fenoterol, atropine, styrene oxide
      and dansyl amino acids can be baseline or partially separated on the current CSP
      under reversed phase high performance liquid chromatography (RP-HPLC). The
      selectivity and resolution of 4NPh-OPr reached 5.25 and 13.97, which is an
      exciting achievement for the enantioseparations by CD CSPs.

PMID- 25614193
TI  - Higher iron pearl millet (Pennisetum glaucum L.) provides more absorbable iron
      that is limited by increased polyphenolic content.
AB  - BACKGROUND: Our objective was to compare the capacity of iron (Fe) biofortified
      and standard pearl millet (Pennisetum glaucum L.) to deliver Fe for hemoglobin
      (Hb)-synthesis. Pearl millet (PM) is common in West-Africa and India, and is well
      adapted to growing areas characterized by drought, low-soil fertility, and high
      temperature. Because of its tolerance to difficult growing conditions, it can be
      grown in areas where other cereal crops, such as maize, would not survive. It
      accounts for approximately 50% of the total world-production of millet. Given the
      widespread use of PM in areas of the world affected by Fe-deficiency, it is
      important to establish whether biofortified-PM can improve Fe-nutriture. METHODS:
      Two isolines of PM, a low-Fe-control ("DG-9444", Low-Fe) and biofortified ("ICTP
      8203 Fe",High-Fe) in Fe (26 MUg and 85 MUg-Fe/g, respectively) were used. PM
      based diets were formulated to meet the nutrient requirements for the broiler
      (Gallus-gallus) except for Fe (Fe concentrations were 22.1+/-0.52 and 78.6+/-0.51
      MUg-Fe/g for the Low-Fe and High-Fe diets, respectively). For 6-weeks, Hb, feed
      consumption and body-weight were measured (n = 12). RESULTS: Improved Fe-status
      was observed in the High-Fe group, as suggested by total-Hb-Fe values (15.5+/-0.8
      and 26.7+/-1.4 mg, Low-Fe and High-Fe respectively, P<0.05). DMT-1, DcytB, and
      ferroportin mRNA-expression was higher (P<0.05) and liver-ferritin was lower
      (P>0.05) in the Low-Fe group versus High-Fe group. In-vitro comparisons indicated
      that the High-Fe PM should provide more absorbable-Fe; however, the cell-ferritin
      values of the in-vitro bioassay were very low. Such low in-vitro values, and as
      previously demonstrated, indicate the presence of high-levels of polyphenolic
      compounds or/and phytic-acid that inhibit Fe-absorption. LC/MS-analysis yielded
      15 unique parent aglycone polyphenolic-compounds elevated in the High-Fe line,
      corresponding to m/z = 431.09. CONCLUSIONS: The High-Fe diet appeared to deliver
      more absorbable-Fe as evidenced by the increased Hb and Hb-Fe status. Results
      suggest that some PM varieties with higher Fe contents also contain elevated
      polyphenolic concentrations, which inhibit Fe-bioavailability. Our observations
      are important as these polyphenols-compounds represent potential targets which
      can perhaps be manipulated during the breeding process to yield improved dietary
      Fe-bioavailability. Therefore, the polyphenolic and phytate profiles of PM must
      be carefully evaluated in order to further improve the nutritional benefit of
      this crop.

PMID- 25614194
TI  - Tentorial meningiomas: surgical options, clinical feature and management
      experience in 43 patients.
AB  - OBJECTIVE: To investigate the optimal treatments and the prognostic factors of
      the tentorial meningiomas (TMs). METHODS: The data of clinical symptom, imaging
      examination, surgical approaches as well as the influence factors of gross total
      resection (GTR) of 43 TMs cases were analyzed retrospectively. RESULT: Imaging
      examinations of computer tomography (CT) and magnetic resonance image (MRI) were
      performed in all 43 cases. The angiographies such as computer tomography
      angiography (CTA), digital subtraction angiography (DSA), magnetic resonance
      angiography (MRA) and magnetic resonance venography (MRV) were obtained in part
      of these cases. The TMs can be classified into 2 types as superior/inferior to
      the tentorium, and subtypes as medial/lateral, anterior/middle/posterior
      according its location and the origination of the tumor. Six different surgical
      approaches were utilized in the study mainly depending on the tumor location and
      the surgeon's preference. CT scan was performed in all patients 6h after the
      operation. Follow-up MRI with contrast was also obtained 3 months later.
      Simpson's grade of excision was applied. GTR was defined as Simpson grade I and
      II, and was acquired in 34 cases, in which Simpson grade I resection was
      accomplished in 15 cases, and subtotal resection (STR) was defined as more than
      90% of the tumor volume was removed and was acquired in 7 cases; histopathology
      revealed 34 benign (grade I), 8 atypical (grade II), and 1 malignant (grade III)
      cases. CONCLUSION: Elaborate imaging examination, microsurgical skills as well as
      the choices of approaches and management of the sinus involved are the main
      prognostic factors of the TMs.

PMID- 25614195
TI  - OCT measurements of optic nerve head changes in idiopathic intracranial
      hypertension.
AB  - OBJECTIVE: Severity of papilledema and vision loss constitute a basis for
      therapeutic intervention in idiopathic intracranial hypertension (IIH), but both
      are often subjective and insensitive in guiding clinical management. The aim of
      this study was to identify reliable and sensitive measurements of optic nerve
      head (ONH) and macula, to provide objective guidance for prognostic evaluation
      and treatment in IIH. We analyzed potential of spectral domain optical coherence
      tomography (SD-OCT), to measure neuro-retinal rim thickness and area, optic cup
      to-disc ratio (C/D) and cup volume of ONH which have not previously been reported
      in IIH. In parallel, thickness of peripapillary retinal nerve fiber layer (RNFL)
      and macular ganglion cell layer (GCL) together with inner plexiform layer (IPL)
      (GCL-IPL) were examined. RESULTS: All 7 enrolled IIH patients had increased neuro
      retinal rim thickness (p<0.01 for both eyes) and rim area (p<0.05), decreased C/D
      (p<0.01) and optic cup volume (p<0.01) when compared to findings in 18 sex- and
      age-matched healthy controls (HC). In a longitudinal study, two IIH patients were
      followed repetitively by SD-OCT before and after measurement of intracranial
      pressure (ICP) and removal of cerebrospinal fluid (CSF) by lumbar puncture. Rim
      thickness and area, C/D and optic cup volume remained altered. RNFL thickness may
      change with very high ICP, but not immediately after CSF removal. GCL-IPL
      thickness was unchanged irrespective of ICP change or CSF removal. CONCLUSION: SD
      OCT allows detection of ONH changes even in subtle IIH without papilledema and
      has potential for routine use in IIH.

PMID- 25614196
TI  - Therapy of older persons with acute myeloid leukemia.

PMID- 25614197
TI  - The benefit of microsatellite instability is attenuated by chemotherapy in stage
      II and stage III gastric cancer: Results from a large cohort with subgroup
      analyses.
AB  - We previously reported that the prognosis of microsatellite instability high (MSI
      H) gastric cancer is similar to that of MSI-low/microsatellite stable (MSI-L/MSS)
      gastric cancer. The reason for this seemed to be related to the effects of
      chemotherapy. To verify this hypothesis, we expanded the study population and
      reanalyzed the prognosis of MSI-H gastric cancer. Data from 1,276 patients with
      Stage II and III gastric cancer who underwent gastrectomy with curative intent
      between January 2005 and June 2010 were reviewed. The prognosis of MSI-H tumors
      in comparison with MSI-L/MSS tumors was analyzed, according to the administration
      of chemotherapy and other clinicopathologic features. A total of 361 (28.3%)
      patients did not receive chemotherapy (MSI-H = 47 and MSI-L/MSS = 314), whereas
      915 (71.7%) patients did receive chemotherapy (MSI-H = 58 and MSI-L/MSS = 857).
      The hazard ratio of MSI-H versus MSI-L/MSS was 0.49 (95% confidence interval:
      0.26-0.94, p = 0.031) when chemotherapy was not received and 1.16 (95% confidence
      interval: 0.78-1.71, p = 0.466) when chemotherapy was received. In subgroup
      analyses, the prognosis of MSI-H was better in Stage III, women, with lymph node
      metastasis, and undifferentiated histology subgroups when chemotherapy was not
      received. However, in patients treated with chemotherapy, prognosis was worse for
      MSI-H tumors in Stage III, undifferentiated histology, and diffuse type subgroups
      of gastric cancer. In conclusion, MSI-H tumors were associated with a good
      prognosis in Stage II and III gastric cancer when patients were treated by
      surgery alone, and the benefits of MSI-H status were attenuated by chemotherapy.

PMID- 25614198
TI  - Pathways from dieting to weight regain, to obesity and to the metabolic syndrome:
      an overview.
AB  - Every year, scores of millions of people - as diverse as obese and lean,
      teenagers and older adults, sedentary and elite athletes, commoners and
      celebrities - attempt to lose weight on some form of diet. They are often
      encouraged by their parents, friends, health professionals, training coaches, a
      media that promotes a slim image and a diet-industry that in Europe and United
      States alone has an annual turnover in excess of $150 billion. Weight regain is
      generally the rule, with one-third to two-thirds of the weight lost being
      regained within 1 year and almost all is regained within 5 years. With studies of
      the long-term outcomes showing that at least one-third of dieters regain more
      weight than they lost, together with prospective studies indicating that dieting
      during childhood and adolescence predicts future weight gain and obesity, there
      is concern as to whether dieting may paradoxically be promoting exactly the
      opposite of what it is intended to achieve. Does dieting really make people
      fatter? How? Does dieting increase the risks for cardiometabolic diseases as many
      go through repeated cycles of intentional weight loss and unintentional weight
      regain, i.e. through yo-yo dieting or weight cycling? What's new in adipose
      tissue biology pertaining to the mechanisms that drive weight regain? Why does
      exercise not necessarily work in concert with dieting to achieve weight loss and
      prevent weight regain? What 'lessons' are we learning from bariatric surgery
      about the mechanisms by which long-term weight loss seems achievable? It is these
      questions, against a background of preoccupation with dieting, that recent
      advances and controversies relevant to the theme of 'Pathways from dieting to
      weight regain, to obesity and to the metabolic syndrome' are addressed in this
      overview and the eight review articles in this supplement reporting the
      proceedings of the 7th Fribourg Obesity Research Conference. 

PMID- 25614199
TI  - Dieting and weight cycling as risk factors for cardiometabolic diseases: who is
      really at risk?
AB  - Despite the poor prognosis of dieting in obesity management, which often results
      in repeated attempts at weight loss and hence weight cycling, the prevalence of
      dieting has increased continuously in the past decades in parallel to the
      steadily increasing prevalence of obesity. However, dieting and weight cycling
      are not limited to those who are obese or overweight as substantial proportions
      of the various population groups with normal body weight also attempt to lose
      weight. These include young and older adults as well as children and adolescents
      who perceive themselves as too fat (due to media, parental and social pressures),
      athletes in weight-sensitive competitive sports (i.e. mandatory weight
      categories, gravitational and aesthetic sports) or among performers for whom a
      slim image is professionally an advantage. Of particular concern is the emergence
      of evidence that some of the potentially negative health consequences of repeated
      dieting and weight cycling are more readily seen in people of normal body weight
      rather than in those who are overweight or obese. In particular, several
      metabolic and cardiovascular risk factors associated with weight cycling in
      normal-weight individuals have been identified from cross-sectional and
      prospective studies as well as from studies of experimentally induced weight
      cycling. In addition, findings from studies of experimental weight cycling have
      reinforced the notion that fluctuations of cardiovascular risk variables (such as
      blood pressure, heart rate, sympathetic activity, blood glucose, lipids and
      insulin) with probable repeated overshoots above normal values during periods of
      weight regain put an additional stress on the cardiovascular system. As the
      prevalence of diet-induced weight cycling is increasing due to the opposing
      forces of an 'obesigenic' environment and the media pressure for a slim figure
      (that even targets children), dieting and weight cycling is likely to become an
      increasingly serious public health issue. 

PMID- 25614200
TI  - Dieting: proxy or cause of future weight gain?
AB  - The relationship between dieting and body mass has a long and controversial
      history. This paper aims to help resolve this issue by making two key
      distinctions. The first is between dieting as a cause of weight gain/regain and
      as a proxy risk factor for identifying non-obese individuals prone to weight gain
      for reasons other than dieting. The second is between the body mass that is
      attained following one or more weight loss/regain cycles and the body mass that
      might have been reached had dieting never been undertaken. Evidence is reviewed
      on the relation between recent diet-induced weight loss and sustained weight loss
      (weight suppression), on the one hand, and weight regain, on the other hand.
      Furthermore, the reason that a history of dieting in non-obese individuals
      reflects a susceptibility to future weight gain is explained. It is concluded
      that (i) diet-induced weight loss hastens weight regain but a history of weight
      loss diets does not cause weight gain beyond that which would occur in the
      absence of dieting, and (ii) weight loss dieting in non-obese individuals does
      not cause future weight gain but is simply a proxy risk factor reflecting a
      personal vulnerability to weight gain and living in an obesogenic environment. 

PMID- 25614201
TI  - How dieting makes the lean fatter: from a perspective of body composition
      autoregulation through adipostats and proteinstats awaiting discovery.
AB  - Whether dieting makes people fatter has been a subject of considerable
      controversy over the past 30 years. More recent analysis of several prospective
      studies suggest, however, that it is dieting to lose weight in people who are in
      the healthy normal range of body weight, rather than in those who are overweight
      or obese, that most strongly and consistently predict future weight gain. This
      paper analyses the ongoing arguments in the debate about whether repeated dieting
      to lose weight in normal-weight people represents unsuccessful attempts to
      counter genetic and familial predispositions to obesity, a psychosocial reaction
      to the fear of fatness or that dieting per se confers risks for fatness and hence
      a contributing factor to the obesity epidemic. In addressing the biological
      plausibility that dieting predisposes the lean (rather than the overweight or
      obese) to regaining more body fat than what had been lost (i.e. fat
      overshooting), it integrates the results derived from the re-analysis of body
      composition data on fat mass and fat-free mass (FFM) losses and recoveries from
      human studies of experimental energy restriction and refeeding. These suggest
      that feedback signals from the depletion of both fat mass (i.e. adipostats) and
      FFM (i.e. proteinstats) contribute to weight regain through the modulation of
      energy intake and adaptive thermogenesis, and that a faster rate of fat recovery
      relative to FFM recovery (i.e. preferential catch-up fat) is a central outcome of
      body composition autoregulation in lean individuals. Such a temporal
      desynchronization in the restoration of the body's fat vs. FFM results in a state
      of hyperphagia that persists beyond complete recovery of fat mass and
      interestingly until FFM is fully recovered. However, as this completion of FFM
      recovery is also accompanied by fat deposition, excess fat accumulates. In other
      words, fat overshooting is a prerequisite to allow complete recovery of FFM. This
      confers biological plausibility for post-dieting fat overshooting - which through
      repeated dieting and weight cycling would increase the risks for trajectories
      from leanness to fatness. Given the increasing prevalence of dieting in normal
      weight female and male among young adults, adolescents and even children who
      perceive themselves as too fat (due to media, family and societal pressures),
      together with the high prevalence of dieting for optimizing performance among
      athletes in weight-sensitive sports, the notion that dieting and weight cycling
      may be predisposing a substantial proportion of the population to weight gain and
      obesity deserves greater scientific scrutiny. 

PMID- 25614202
TI  - Deep body composition phenotyping during weight cycling: relevance to metabolic
      efficiency and metabolic risk.
AB  - Weight cycling may lead to adverse effects on metabolic efficiency (i.e. adaptive
      thermogenesis or 'metabolic slowing') and metabolic risks (e.g. increased risk
      for insulin resistance and the metabolic syndrome). In order to investigate these
      topics, the partitioning of fat and lean mass (i.e. the change in the proportion
      of both compartments) needs to be extended to the organ and tissue level because
      metabolic risk differs between adipose tissue depots and lean mass is
      metabolically heterogeneous being composed of organs and tissues differing in
      metabolic rate. Contrary to data obtained with severe weight loss and regain in
      lean people, weight cycling most likely has no adverse effects on fat
      distribution and metabolic risk in obese patients. There is even evidence for an
      increased ability of fat storage in subcutaneous fat depots (at the trunk in men
      and at the limbs in women) with weight cycling that may provide a certain
      protection from ectopic lipid deposition and thus explain the preservation of a
      favourable metabolic profile despite weight regain. On the other hand, the mass
      specific metabolic rate of lean mass may increase with weight gain and decrease
      with weight loss mainly because of an increase and respective decrease in the
      proportion (and/or activity) of metabolically active organ mass. Obese people
      could therefore have a higher slope of the regression line between resting energy
      expenditure (REE) and fat-free mass that leads to an overestimation of metabolic
      efficiency when applied to normalize REE data after weight loss. Furthermore, in
      addressing the impact of macronutrient composition of the diet on partitioning of
      lean and fat mass, and the old controversy about whether a calorie is a calorie,
      we discuss recent evidence in support of a low glycaemic weight maintenance diet
      in countering weight regain and challenge this concept for weight loss by
      proposing the opposite. 

PMID- 25614204
TI  - Monocarboxylate transporters: new players in body weight regulation.
AB  - Over the last two decades, several genes have been identified that appear to play
      a role in the regulation of energy homeostasis and body weight. For a small
      subset of them, a reduction or an absence of expression confers a resistance to
      the development of obesity. Recently, a knockin mouse for a member of the
      monocarboxylate transporter (MCT) family, MCT1, was demonstrated to exhibit a
      typical phenotype of resistance to diet-induced obesity and a protection from its
      associated metabolic perturbations. Such findings point out at MCTs as putatively
      new therapeutic targets in the context of obesity. Here, we will review what is
      known about MCTs and their possible metabolic roles in different organs and
      tissues. Based on the description of the phenotype of the MCT1 knockin mouse, we
      will also provide some insights about their putative roles in weight gain
      regulation. 

PMID- 25614203
TI  - The role for adipose tissue in weight regain after weight loss.
AB  - Weight regain after weight loss is a substantial challenge in obesity
      therapeutics. Dieting leads to significant adaptations in the homeostatic system
      that controls body weight, which promotes overeating and the relapse to obesity.
      In this review, we focus specifically on the adaptations in white adipose tissues
      that contribute to the biological drive to regain weight after weight loss.
      Weight loss leads to a reduction in size of adipocytes and this decline in size
      alters their metabolic and inflammatory characteristics in a manner that
      facilitates the clearance and storage of ingested energy. We present the
      hypothesis whereby the long-term signals reflecting stored energy and short-term
      signals reflecting nutrient availability are derived from the cellularity
      characteristics of adipose tissues. These signals are received and integrated in
      the hypothalamus and hindbrain and an energy gap between appetite and metabolic
      requirements emerges and promotes a positive energy imbalance and weight regain.
      In this paradigm, the cellularity and metabolic characteristics of adipose
      tissues after energy-restricted weight loss could explain the persistence of a
      biological drive to regain weight during both weight maintenance and the dynamic
      period of weight regain. 

PMID- 25614205
TI  - Appetite control and energy balance: impact of exercise.
AB  - Exercise is widely regarded as one of the most valuable components of behaviour
      that can influence body weight and therefore help in the prevention and
      management of obesity. Indeed, long-term controlled trials show a clear dose
      related effect of exercise on body weight. However, there is a suspicion,
      particularly fuelled by media reports, that exercise serves to increase hunger
      and drive up food intake thereby nullifying the energy expended through activity.
      Not everyone performing regular exercise will lose weight and several
      investigations have demonstrated a huge individual variability in the response to
      exercise regimes. What accounts for this heterogeneous response? First, exercise
      (or physical activity) through the expenditure of energy will influence the
      energy balance equation with the potential to generate an energy deficit.
      However, energy expenditure also influences the control of appetite (i.e. the
      physiological and psychological regulatory processes underpinning feeding) and
      energy intake. This dynamic interaction means that the prediction of a resultant
      shift in energy balance, and therefore weight change, will be complicated. In
      changing energy intake, exercise will impact on the biological mechanisms
      controlling appetite. It is becoming recognized that the major influences on the
      expression of appetite arise from fat-free mass and fat mass, resting metabolic
      rate, gastric adjustment to ingested food, changes in episodic peptides including
      insulin, ghrelin, cholecystokinin, glucagon-like peptide-1 and tyrosine-tyrosine,
      as well as tonic peptides such as leptin. Moreover, there is evidence that
      exercise will influence all of these components that, in turn, will influence the
      drive to eat through the modulation of hunger (a conscious sensation reflecting a
      mental urge to eat) and adjustments in postprandial satiety via an interaction
      with food composition. The specific actions of exercise on each physiological
      component will vary in strength from person to person (according to individual
      physiological characteristics) and with the intensity and duration of exercise.
      Therefore, individual responses to exercise will be highly variable and difficult
      to predict. 

PMID- 25614208
TI  - N-doped carbon networks: alternative materials tracing new routes for activating
      molecular hydrogen.
AB  - The fragmentation of molecular hydrogen on N-doped carbon networks was
      investigated by using molecular (polyaromatic macrocycles) as well as truncated
      and periodic (carbon nanotubes) models. The computational study was focused on
      the ergonicity analysis of the reaction and on the properties of the transition
      states involved when constellations of three or four pyridinic nitrogen atom
      defects are present in the carbon network. Calculations show that whenever N
      defects are embedded in species characterized by large conjugated pi-systems,
      either in polyaromatic macrocycles or carbon nanotubes, the corresponding H2 bond
      cleavage is largely exergonic. The fragmentation Gibbs free energy is affected by
      the final arrangement of the hydrogen atoms on the defect and by the extension of
      the pi-electron cloud, but it is not influenced by the curvature of the system. 

PMID- 25614209
TI  - Acceleration of acetal hydrolysis by remote alkoxy groups: evidence for
      electrostatic effects on the formation of oxocarbenium ions.
AB  - In contrast to observations with carbohydrates, experiments with 4-alkoxy
      substituted acetals indicate that an alkoxy group can accelerate acetal
      hydrolysis by up to 20-fold compared to substrates without an alkoxy group. The
      acceleration of ionization in more flexible acetals can be up to 200-fold when
      compensated for inductive effects. 

PMID- 25614210
TI  - A multivariate Bayesian model for embryonic growth.
AB  - Most longitudinal growth curve models evaluate the evolution of each of the
      anthropometric measurements separately. When applied to a 'reference population',
      this exercise leads to univariate reference curves against which new individuals
      can be evaluated. However, growth should be evaluated in totality, that is, by
      evaluating all body characteristics jointly. Recently, Cole et al. suggested the
      Superimposition by Translation and Rotation (SITAR) model, which expresses
      individual growth curves by three subject-specific parameters indicating their
      deviation from a flexible overall growth curve. This model allows the
      characterization of normal growth in a flexible though compact manner. In this
      paper, we generalize the SITAR model in a Bayesian way to multiple dimensions.
      The multivariate SITAR model allows us to create multivariate reference regions,
      which is advantageous for prediction. The usefulness of the model is illustrated
      on longitudinal measurements of embryonic growth obtained in the first semester
      of pregnancy, collected in the ongoing Rotterdam Predict study. Further, we
      demonstrate how the model can be used to find determinants of embryonic growth.

PMID- 25614206
TI  - Appetite and body weight regulation after bariatric surgery.
AB  - Bariatric surgery continues to be remarkably efficient in treating obesity and
      type 2 diabetes mellitus and a debate has started whether it should remain the
      last resort only or also be used for the prevention of metabolic diseases.
      Intense research efforts in humans and rodent models are underway to identify the
      critical mechanisms underlying the beneficial effects with a view towards non
      surgical treatment options. This non-systematic review summarizes and interprets
      some of this literature, with an emphasis on changes in the controls of appetite.
      Contrary to earlier views, surgery-induced reduction of energy intake and
      subsequent weight loss appear to be the main drivers for rapid improvements of
      glycaemic control. The mechanisms responsible for suppression of appetite,
      particularly in the face of the large weight loss, are not well understood.
      Although a number of changes in food choice, taste functions, hedonic evaluation,
      motivation and self-control have been documented in both humans and rodents after
      surgery, their importance and relative contribution to diminished appetite has
      not yet been demonstrated. Furthermore, none of the major candidate mechanisms
      postulated in mediating surgery-induced changes from the gut and other organs to
      the brain, such as gut hormones and sensory neuronal pathways, have been
      confirmed yet. Future research efforts should focus on interventional rather than
      descriptive approaches in both humans and rodent models. 

PMID- 25614211
TI  - Expression of MUC1 and CD176 (Thomsen-Friedenreich antigen) in papillary thyroid
      carcinomas.
AB  - The incidence of thyroid cancer has appeared as an increasing trend globally,
      especially in Asian countries. In this study, the expression of mucin-1 (MUC1)
      and Thomsen-Friedenreich antigen, Galbeta1-3GalNAcalpha1-R (CD176) was
      investigated by immunohistochemistry in papillary thyroid carcinomas (PTCs),
      which accounts for approximately 80 % of all thyroid cancer. We found that 78 %
      of PTC overexpressed MUC1. Importantly, we observed firstly that CD176 was
      expressed in 63 % of PTC, but was faintly or not expressed in normal thyroid
      tissues and benign thyroid disease tissues, indicating that CD176 is also a
      tumour-associated antigen for PTCs. Moreover, expression of CD176 was strongly
      correlated with MUC1 by immunohistochemical staining in PTCs. Furthermore, we
      used the immunochemical method to confirm that MUC1 is a common and main carrier
      of CD176 in PTCs. Our data demonstrated that MUC1 and CD176 might be promising
      biomarkers for thyroid cancer.

PMID- 25614212
TI  - Synchronous diagnosis of metastatic cancer to the thyroid is associated with poor
      prognosis.
AB  - The incidence and histopathological characteristics of metastatic cancers to the
      thyroid (MCT) are different in various geographic areas. The aim of this study
      was to elucidate the clinical features of MCT, including histocytological
      diagnosis and therapeutic outcomes. A retrospective analysis of patients with
      thyroid cancer treated and followed up at the Chang Gung Medical Center in Linkou
      was performed. Among 3957 patients with thyroid cancer, a total of 56 patients
      with MCT were evaluated. Of them, 47 patients (83.9 %) were diagnosed with
      malignancy or suspected malignancy via fine needle aspiration cytology of the
      thyroid. Synchronous primary cancers were diagnosed in 44 of the patients with
      MCT. Of the MCT, metastasis of lung cancer to the thyroid was the leading
      category. Other primary sites of MCT were the head and neck, gastrointestinal
      tract, kidneys, breast, cervix, and unknown primary site. The mean 5-, 10-, 20-,
      and 60-month survival rates were 46.4, 32.1, 21.4, and 7.9 % for the patients.
      Patients with metachronous thyroid carcinoma had significantly better survival
      than patients with synchronous cancer. In conclusions, the incidence of MCT in
      patients with thyroid cancer is low; however, the prognosis of patients with MCT
      is poor, especially in patients diagnosed with synchronous primary tumors. In
      this study, MCT commonly originated in organs located near the thyroid, such as
      the lungs, head, and neck. Close monitoring of these malignancies may improve the
      prognosis of patients with MCT in the future.

PMID- 25614213
TI  - Laparoscopic repair of rectal foreign body perforation without protective
      colostomy (with video).

PMID- 25614214
TI  - High doses of bisphosphonates reduce osteoblast-like cell proliferation by
      arresting the cell cycle and inducing apoptosis.
AB  - OBJECTIVES: The study objective was to evaluate the effect on osteoblast growth
      of high concentrations of three nitrogen-containing bisphosphonates (pamidronate,
      alendronate, and ibandronate) and one non-nitrogen-containing bisphosphonate
      (clodronate), using the MG-63 cell line as an osteoblast model, in order to
      determine the role of osteoblasts in bisphosphonate-related osteonecrosis of the
      jaw (BRONJ). MATERIALS AND METHODS: Osteoblasts were incubated in culture medium
      with different doses of pamidronate, alendronate, ibandronate or clodronate. The
      proliferative capacity of the osteoblasts was determined by spectrophotometry
      (MTT-based) at 24 h of culture. Flow cytometry was used to determine the
      percentage of cells in each cell cycle phase (G0/G1, G2/M, and S) and to
      discriminate apoptotic cell death from necrotic cell death in the cell cycle at
      24 h of treatment. RESULTS: All the bisphosphonates assayed produced a
      significant and dose-dependent reduction in MG-63 proliferation at the high doses
      assayed (10(-4) and 5 * 10(-5) M) in comparison with controls (p <0.001). Cell
      cycle study revealed that all assayed bisphosphonates significantly arrested the
      cell cycle in phase G0/G1 at doses of 10(-4) and 5 * 10(-5) M, increasing the
      percentage of cells in this phase (p <0.05). Apoptosis/necrosis studies showed
      significant changes compared with control cells, with an increased percentage of
      cells in apoptosis after treatment with 10(-4) or 5 * 10(-5) M of pamidronate,
      alendronate, ibandronate, or clodronate (p <0.05). CONCLUSIONS: High doses of
      nitrogen-containing or non-nitrogen-containing bisphosphonates can reduce the
      proliferation of MG-63 osteoblast-like cells by arresting the cell cycle and
      inducing apoptosis/necrosis.

PMID- 25614215
TI  - Diffusion tensor imaging focusing on lower cervical spinal cord using 2D reduced
      FOV interleaved multislice single-shot diffusion-weighted echo-planar imaging:
      comparison with conventional single-shot diffusion-weighted echo-planar imaging.
AB  - PURPOSE: To evaluate the performance of diffusion tensor imaging (DTI) of the
      cervical spinal cord by comparing 2-dimensional standard single-shot interleaved
      multisection inner volume diffusion-weighted echo-planar imaging (2D ss-IMIV
      DWEPI) and conventional 2D ss-DWEPI in a clinical population, focusing on the
      lower cervical spinal cord. MATERIALS AND METHODS: From July to September 2013, a
      total of 23 patients who underwent cervical spinal MR imaging with DTI were
      retrospectively enrolled in this study (M:F=7:16, mean age 45years, age range 24
      76 years). Exclusion criteria were: previous prosthesis insertion (n=5),
      syringomyelia on T2-weighted imaging (n=4), and spinal cord tumor (n=0). All MRI
      examinations were performed using 3.0T imaging with a phased-array spine coil
      including two different 2D reduced FOV DTI sequences: 2D ss-IMIV-DWEPI (iDTI) and
      2D ss-DWEPI without interleaving (cDTI). For quantitative analysis, two
      musculoskeletal radiologists who were blinded to the sequence measured fractional
      anisotropy (FA) and apparent diffusion coefficient (ADC) values throughout the
      whole cervical spinal cord (C1-T1). For qualitative analysis, the readers rated
      each image based on spinal cord distortion, dural margin delineation, and
      depiction of intervertebral disc. Quantitative and qualitative evaluations were
      analyzed separately for upper and lower segments. The t-test was used for
      quantitative analysis and two-way analysis of variance (ANOVA) and t-tests were
      performed for qualitative analysis. RESULTS: FA was significantly higher and ADC
      was significantly lower on iDTI compared with cDTI (0.679 versus 0.563,
      respectively, for FA; 631 versus 1026, respectively, for ADC; p<0.001), and this
      was consistently observed in the lower segment of the spinal cord. The reviewers
      rated iDTI as superior in terms of all assessed characteristics. For qualitative
      analysis, the mean iDTI score was significantly higher than the cDTI score for
      both the lower and upper segments (p<0.001). CONCLUSION: 2D rFOV ss-IMIV-DWEPI
      demonstrated higher performance than conventional 2D rFOV ss-DWEPI in terms of
      improving image quality, even in the lower segment of the cervical spinal cord.

PMID- 25614216
TI  - Short T2 tissue imaging with the Pointwise Encoding Time reduction with Radial
      Acquisition (PETRA) sequence: the additional value of fat saturation and
      subtraction in the meniscus.
AB  - PURPOSE: The purposes of this study were (1) to compare single-echo PETRA with
      dual-echo PETRA using in vivo MR imaging, (2) to compare non-fat-saturated PETRA
      with fat-saturated PETRA using a 3-T clinical MR scanner, and (3) to determine
      the effect of the adequate sequence and post-processing method. MATERIALS AND
      METHODS: Twenty-two patients underwent dual-echo 3D PETRA sequence knee MR
      imagining (TE of 70MUs and 2.3ms) with and without fat-saturation using a 3T
      clinical MR scanner (Magnetom Trio, Siemens, Erlangen, Germany). The study
      population was classified into two groups: (1) normal meniscus on conventional MR
      images with no related physical examination on medical records and (2) meniscal
      degeneration or tear. We reformatted four image sets: (1) ultrashort TE signal
      without fat-saturation, (2) ultrashort TE signal with fat-saturation, (3)
      weighted-subtraction image of dual-echo PETRA images without fat-saturation, and
      (4) weighted-subtraction image with fat-saturation. For the weighted-subtraction
      images, the ultrashort TE image was rescaled relative to the second echo image
      with weighting factors from 0.6 based on SNR and CNR analyses. For quantitative
      assessment, the mean signal intensities inside user-drawn regions of interest
      (ROIs) were drawn and recorded. For statistical analyses, the t-test was used to
      compare the two groups and effect size was used for comparison of the
      discrimination power. RESULTS: In all image sets, the mean signal intensity
      values were lower in patients with meniscal degeneration/tear compared to
      controls on both fat-saturated and non-fat-saturated MR images. The single-echo
      ultrashort TE images showed higher effect sizes than the weighted-subtraction
      image of dual-echo images. CONCLUSION: We demonstrated that there was
      significantly lower signal intensity on ultrashort TE PETRA images in the
      patients with meniscal pathologies. In addition, the single-echo of the
      ultrashort TE PETRA images echo time could be a more sensitive indicator between
      normal and pathologic meniscus conditions in patients.

PMID- 25614218
TI  - Screening for a gene deletion mutant whose temperature sensitivity is suppressed
      by FK506 in budding yeast and its application for a positive screening for drugs
      inhibiting calcineurin.
AB  - Calcineurin, which is a Ca(2+)/calmodulin-dependent protein phosphatase, is a key
      mediator in calcium signaling in diverse biological processes and of clinical
      importance as the target of the immunosuppressant FK506. To identify a mutant(s)
      in which calcineurin is activated, inhibiting cellular growth as a result, we
      screened for a mutant(s) whose temperature sensitivity would be suppressed by
      FK506 from the budding yeast non-essential gene deletion library. We found that
      the temperature sensitivity of cells in which the conserved Verprolin VRP1 gene
      had been deleted, which gene is required for actin organization and endocytosis,
      was suppressed by either FK506 or by cnb1 deletion. Indeed, the calcineurin
      activity increased significantly in the ?vrp1 cells. Finally, we demonstrated
      that the ?vrp1 strain to be useful as an indicator in a positive screening for
      bioactive compounds inhibiting calcineurin. 

PMID- 25614217
TI  - N-glycosylation of cholera toxin B subunit in Nicotiana benthamiana: impacts on
      host stress response, production yield and vaccine potential.
AB  - Plant-based transient overexpression systems enable rapid and scalable production
      of subunit vaccines. Previously, we have shown that cholera toxin B subunit
      (CTB), an oral cholera vaccine antigen, is N-glycosylated upon expression in
      transgenic Nicotiana benthamiana. Here, we found that overexpression of
      aglycosylated CTB by agroinfiltration of a tobamoviral vector causes massive
      tissue necrosis and poor accumulation unless retained in the endoplasmic
      reticulum (ER). However, the re-introduction of N-glycosylation to its original
      or an alternative site significantly relieved the necrosis and provided a high
      CTB yield without ER retention. Quantitative gene expression analysis of PDI,
      BiP, bZIP60, SKP1, 26Salpha proteasome and PR1a, and the detection of
      ubiquitinated CTB polypeptides revealed that N-glycosylation significantly
      relieved ER stress and hypersensitive response, and facilitated the
      folding/assembly of CTB. The glycosylated CTB (gCTB) was characterized for
      potential vaccine use. Glycan profiling revealed that gCTB contained
      approximately 38% plant-specific glycans. gCTB retained nanomolar affinity to GM1
      ganglioside with only marginal reduction of physicochemical stability and induced
      an anti-cholera holotoxin antibody response comparable to native CTB in a mouse
      oral immunization study. These findings demonstrated gCTB's potential as an oral
      immunogen and point to a potential role of N-glycosylation in increasing
      recombinant protein yields in plants. 

PMID- 25614219
TI  - TNF-alpha -308 G/A as a risk marker of cervical cancer progression in the Polish
      population.
AB  - BACKGROUND AND OBJECTIVE: There are inconclusive data on the tumor necrosis
      factor-alpha (TNF-alpha) -308 G/A (rs1800629) polymorphism as a risk factor for
      cervical carcinogenesis. METHODS: Using high-resolution melting curve analysis,
      we investigated the prevalence of the TNF-alpha -308 G/A transition (rs1800629)
      in patients with cervical cancer (n = 362) and control subjects (n = 399).
      RESULTS: The p trend value calculated for the TNF-alpha -308 G/A transition was
      statistically significant (p trend = 0.026) for all patients. Logistic regression
      analysis with adjustment for age demonstrated that the A/A versus G/G genotype
      was significantly associated with cervical tumors. The adjusted odds ratio (OR)
      was 1.599 (95 % confidence interval [CI] 1.017-2.513; p = 0.042). Stratification
      of patients on the basis of the tumor stage revealed no contribution of the TNF
      alpha -308 G/A transition to cervical cancer in stages I and II. However, we
      found a significant trend for the p value, as well as the contribution of TNF
      alpha -308 G/A to cervical cancer, in stages III and IV. The p trend value was
      0.003 in this group of patients. Moreover, logistic regression analysis with
      adjustment for age demonstrated that the adjusted OR for A/A versus G/G was 2.014
      (95 % CI 1.122-3.613; p = 0.019) and the adjusted OR for A/A or A/G versus G/G
      was 1.583 (95 % CI 1.025-2.444; p = 0.038) for cervical cancer in stages III and
      IV. CONCLUSION: Our results indicate that the TNF-alpha -308 G/A transition is a
      risk factor for cervical cancer, particularly in stages III and IV.

PMID- 25614220
TI  - Vitamin D-related changes in intracranial volume in older adults: a quantitative
      neuroimaging study.
AB  - OBJECTIVES: Vitamin D is involved in skeletal and brain health. Recently, serum
      25-hydroxyvitamin D (25OHD) concentration was found to be inversely correlated
      with intracranial volume in younger adults. Since hypovitaminosis D is most
      common in older adults, our objective was to determine whether this inverse
      correlation between 25OHD concentration and intracranial volume also occurred in
      older adults. STUDY DESIGN: Cross-sectional study. MAIN OUTCOME MEASURES: One
      hundred and ten Caucasian older community-dwellers (mean, 71.7+/-5.7 years; 45.5%
      female) received a blood test and an MRI of the brain at the same period. The
      intracranial volume and the subvolumes of cerebrospinal fluid, total brain,
      infratentorial brain, supratentorial brain, total white matter, total gray
      matter, cortical gray matter and subcortical gray matter were measured using
      FreeSurfer volumetry on T1-weighted images. Vitamin D insufficiency was defined
      as serum 25OHD<50nmol/L. Age, gender, body mass index, education level, use of
      vitamin D supplements, season of evaluation, serum concentrations of calcium and
      thyroid stimulating hormone were used as covariables in the analysis. RESULTS: We
      found that participants with vitamin D insufficiency (n=41) had greater
      intracranial volume than those without (1555.0+/-1379.2cm(3) versus 1488.0+/
      167.4cm(3), P=0.033). Serum 25OHD concentration was cross-sectionally associated
      with decreased intracranial volume in mm(3) (unadjusted beta=-1194.4, P=0.028),
      even after adjustment for covariables (adjusted beta=-994.3, P=0.048). We found
      an inverse correlation of serum 25OHD with intracranial volume (r=-0.21, P=0.028)
      and the volume of white matter (r=-0.20, P=0.033). The other subvolumes did not
      correlate with serum 25OHD concentration. CONCLUSIONS: Serum 25OHD concentration
      was independently and inversely associated with intracranial volume in older
      adults.

PMID- 25614222
TI  - Applying thermodynamic profiling in lead finding and optimization.
AB  - Small-molecule drug discovery involves the optimization of various
      physicochemical properties of a ligand, particularly its binding affinity for its
      target receptor (or receptors). In recent years, there has been growing interest
      in using thermodynamic profiling of ligand-receptor interactions in order to
      select and optimize those ligands that might be most likely to become drug
      candidates with desirable physicochemical properties. The thermodynamics of
      binding is influenced by multiple factors, including hydrogen bonding and
      hydrophobic interactions, desolvation, residual mobility, dynamics and the local
      water structure. This article discusses key issues in understanding the effects
      of these factors and applying this knowledge in drug discovery.

PMID- 25614224
TI  - Anti-inflammatory activity of flavonoids in Nepalese propolis is attributed to
      inhibition of the IL-33 signaling pathway.
AB  - Propolis has been used in folk medicine to improve health and prevent
      inflammatory diseases; however, the components that exhibit its anti-inflammatory
      activity remain unknown. We herein investigated the effects of flavonoids
      isolated from Nepalese propolis on the IL-33 signaling pathway to clarify the
      anti-inflammatory mechanism involved. Of the 8 types of flavonoids isolated from
      Nepalese propolis, 4 types of compounds, such as 3',4'-dihydroxy-4
      methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin, markedly inhibited
      the IL-33-induced mRNA expression of inflammatory genes including IL-6, TNFalpha
      and IL-13 in bone marrow-derived mast cells (BMMC). These four flavonoids also
      inhibited the IL-33-induced activation of nuclear factor kappaB (NF-kappaB),
      which was consistent with their inhibitory effects on cytokine expression. The
      effects of these flavonoids are attributed to inhibition of IL-33-induced
      activation of IKK, which leads to the degradation of IkappaBalpha and nuclear
      localization of NF-kappaB. On the other hand, other flavonoids isolated from
      Nepalese propolis, such as isoliquiritigenin, plathymenin, 7-hydroxyflavanone,
      and (+)-medicarpin, had no effect on the IL-33 signaling pathway or cytokine
      expression. Therefore, these results indicate that 3',4'-dihydroxy-4
      methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin are the substances
      responsible for the anti-inflammatory activity of Nepalese propolis. 

PMID- 25614223
TI  - Assessment of noninvasive acoustic respiration rate monitoring in patients
      admitted to an Emergency Department for drug or alcoholic poisoning.
AB  - To compare respiration rate measurement by an acoustic method and thoracic
      impedance to capnometry as the reference method, in patients at the Emergency
      Department after drug or alcoholic poisoning. In this observational study, 30
      patients aged 18 or older, hospitalized at the Emergency Department for drug or
      alcoholic poisoning, without any contraindication to a face mask and/or a
      cervical acoustic sensor, were included in the study. They benefited from a
      simultaneous recording of their respiration rate by the acoustic method
      (RRa((r)), Masimo Corp., Irvine, CA, USA), by thoracic impedance (Philips
      Intellivue((r)) MP2, Suresnes, France) and by capnometry (Capnostream((r)) 20,
      Oridion, Jerusalem, Israel) through a face mask (Capnomask((r)), Mediplus Ltd,
      Raleigh, NC, USA) for 40-60 min. Of the 86,578 triplets collected, 77,155 (89.1%)
      were exploitable. Median (range) respiration rate measured by capnometry was 18
      (7-29) bpm. Compared to capnometry, bias and limits of agreement were 0.1 +/- 3.8
      bpm for the acoustic method and 0.3 +/- 5.5 bpm for thoracic impedance. The
      proportions of RR values collected by acoustic method or by thoracic impedance
      which differed over 10 or 20% during more than 15 s, compared to capnometry, were
      8.3 versus 14.3, and 1.5 versus 3.8%, respectively (p < 0.0001). The acoustic
      sensor had to be repositioned on three patients. For 11 patients, the
      Capnomask((r)) was removed several times. In patients with drug or alcoholic
      poisoning, the acoustic method seems more accurate than thoracic impedance and
      better tolerated than face mask capnometry.

PMID- 25614225
TI  - Associations between gastrointestinal toxicity, micro RNA and cytokine production
      in patients undergoing myeloablative allogeneic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a
      high risk of treatment related mortality. The primary aim of the present study
      was to examine associations between markers of gastrointestinal toxicity, markers
      of systemic inflammation, and plasma levels of microRNA (miRNA) -155 and -146a
      during the first month after HSCT. The secondary aim was to characterize the
      impact of the toxic-inflammatory response on the function of circulating
      leukocytes during immune recovery. Thirty HSCT patients were included.
      Gastrointestinal injury was monitored by toxicity scores, lactulose-mannitol test
      and plasma citrulline, as a measure of the enterocyte population. Nadir of
      citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and
      plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi
      RNA-146a showed an inverse relation with significantly elevated miRNA-155 and
      decreased miRNA-146a levels, from day 0 to day +28 compared with pre-conditioning
      levels. Citrulline levels below the median at day +7 were associated with higher
      spontaneous production of IL-6 and TNF-alpha as well as higher in vitro
      stimulated production of IL-17A at day +21. This study is the first to
      demonstrate that toxic responses to chemotherapy are accompanied by differential
      regulation of miRNAs with opposing effects on immune regulation. We find that a
      proinflammatory miRNA profile is sustained during the first three weeks after the
      transplantation, indicating that these miRNAs may play a role in the regulation
      of the inflammatory environment during immune reconstitution after HSCT. 

PMID- 25614226
TI  - The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury
      in mice.
AB  - CDDO-Me, initiated in a phase II clinical trial, is a potential useful
      therapeutic agent for cancer and inflammatory dysfunctions, whereas the
      therapeutic efficacy of CDDO-Me on LPS-induced acute lung injury (ALI) has not
      been reported as yet. The purpose of the present study was to explore the
      protective effect of CDDO-Me on LPS-induced ALI in mice and to investigate its
      possible mechanism. BalB/c mice received CDDO-Me (0.5mg/kg, 2mg/kg) or
      dexamethasone (5mg/kg) intraperitoneally 1h before LPS stimulation and were
      sacrificed 6h later. W/D ratio, lung MPO activity, number of total cells and
      neutrophils, pulmonary histopathology, IL-6, IL-1beta, and TNF-alpha in the BALF
      were assessed. Furthermore, we estimated iNOS, IL-6, IL-1beta, and TNF-alpha mRNA
      expression and NO production as well as the activation of the three main MAPKs,
      AkT, IkappaB-alpha and p65. Pretreatment with CDDO-Me significantly ameliorated
      W/D ratio, lung MPO activity, inflammatory cell infiltration, and inflammatory
      cytokine production in BALF from the in vivo study. Additionally, CDDO-Me had
      beneficial effects on the intervention for pathogenesis process at molecular,
      protein and transcriptional levels in vitro. These analytical results provided
      evidence that CDDO-Me could be a potential therapeutic candidate for treating LPS
      induced ALI. 

PMID- 25614227
TI  - Inhalation or ingestion of orthodontic objects in Finland.
AB  - OBJECTIVES: Although inhalation or ingestion of orthodontic appliances can lead
      to serious medical problems, the real incidence of these complications is
      anecdotal. This study had two aims: (1) to define the frequency of accidental
      inhalation/ingestion of orthodontic objects in Finland and (2) to analyze their
      further management. MATERIALS AND METHODS: An electronic, semi-structured
      questionnaire was sent to all members of the Orthodontic Section of Apollonia,
      the Finnish Dental Society (n=251) and the Finnish Federation of Dental
      Hygienists (n=437). After one reminder, 55.8% of dentists and 34.8% of dental
      hygienists responded. RESULTS: In total, 20.0% of the dentists and 6.9% of the
      dental hygienists reported having one patient who had ingested or inhaled an
      orthodontic object. The percentages for two or more cases were 18.6% and 6.9%,
      respectively. According to dentists' answers, the procedures following these
      complications were (1) observation for 2-14 days (n=27), (2) radiologic
      evaluation (n=14), (3) medical emergency (n=6) and (4) dietary instruction (n=4).
      Dental hygienists reported (1) observation (n=9), (2) dietary instruction (n=3)
      and (3) medical emergency (n=1). None of the cases had been life-threatening.
      CONCLUSIONS: Although the risk of inhalation or ingestion of orthodontic objects
      is small and the consequences rarely serious, it should be taken into
      consideration. Prospective patients should be informed of this possibility.

PMID- 25614228
TI  - Interprofessional communication failures in acute care chains: How can we
      identify the causes?
AB  - Although communication failures between professionals in acute care delivery
      occur, explanations for these failures remain unclear. We aim to gain a deeper
      understanding of interprofessional communication failures by assessing two
      different explanations for them. A multiple case study containing six cases (i.e.
      acute care chains) was carried out in which semi-structured interviews, physical
      artifacts and archival records were used for data collection. Data were entered
      into matrices and the pattern-matching technique was used to examine the two
      complementary propositions. Based on the level of standardization and integration
      present in the acute care chains, the six acute care chains could be divided into
      two categories of care processes, with the care chains equally distributed among
      the categories. Failures in communication occurred in both groups. Communication
      routines were embedded within organizations and descriptions of communication
      routines in the entire acute care chain could not be found. Based on the results,
      failures in communication could not exclusively be explained by literature on
      process typology. Literature on organizational routines was useful to explain the
      occurrence of communication failures in the acute care chains. Organizational
      routines can be seen as repetitive action patterns and play an important role in
      organizations, as most processes are carried out by means of routines. The
      results of this study imply that it is useful to further explore the role of
      organizational routines on interprofessional communication in acute care chains
      to develop a solution for failures in handover practices. 

PMID- 25614221
TI  - The re-emergence of natural products for drug discovery in the genomics era.
AB  - Natural products have been a rich source of compounds for drug discovery.
      However, their use has diminished in the past two decades, in part because of
      technical barriers to screening natural products in high-throughput assays
      against molecular targets. Here, we review strategies for natural product
      screening that harness the recent technical advances that have reduced these
      barriers. We also assess the use of genomic and metabolomic approaches to augment
      traditional methods of studying natural products, and highlight recent examples
      of natural products in antimicrobial drug discovery and as inhibitors of protein
      protein interactions. The growing appreciation of functional assays and
      phenotypic screens may further contribute to a revival of interest in natural
      products for drug discovery. 

PMID- 25614229
TI  - International Classification of Functioning, Disability and Health: Catalyst for
      interprofessional education and collaborative practice.
AB  - Patient-centred and community-based care is required for promotion of health
      equity. To enhance patient-centred interprofessional care, the World Health
      Organization recommends using the framework of the International Classification
      of Functioning, Disability and Health (ICF). Stellenbosch University's
      Interprofessional Education and Collaborative Practice (IPECP) strategy has
      promoted using ICF since 2010. Undergraduate medical students on rural clinical
      placements are expected to use ICF in approaching and managing patients.
      Students' ability to develop interprofessional care plans using ICF is assessed
      by a team of preceptors representing various health professions. This study
      explored the experiences of medical students and their preceptors using ICF in
      IPECP, and how patients perceived care received. Associative Group Analysis
      methodology was used to collect data for this study. In total, 68 study
      participants were enrolled of which 37 were medical students, 16 preceptors and
      15 patients. Students found ICF enabled a patient-centred approach and reinforce
      the importance of context. Patients felt listened to and cared for. Preceptors,
      obliged to use ICF, came to appreciate the advantages of interprofessional care,
      promoting mutually beneficial teamwork and job satisfaction. The value of
      integrating IPECP as an authentic learning experience was demonstrated as was ICF
      as a catalyst in pushing boundaries for change. 

PMID- 25614230
TI  - A not cytotoxic nickel concentration alters the expression of neuronal
      differentiation markers in NT2 cells.
AB  - Nickel, a known occupational/environmental hazard, may cross the placenta and
      reach appreciable concentrations in various fetal organs, including the brain.
      The aim of this study was to investigate whether nickel interferes with the
      process of neuronal differentiation. Following a 4 week treatment with retinoic
      acid (10MUM), the human teratocarcinoma-derived NTera2/D1 cell line (NT2 cells)
      terminally differentiate into neurons which recapitulate many features of human
      fetal neurons. The continuous exposure of the differentiating NT2 cells to a not
      cytotoxic nickel concentration (10MUM) increased the expression of specific
      neuronal differentiation markers such as neural cell adhesion molecule (NCAM) and
      microtubule associated protein 2 (MAP2). Furthermore, nickel exposure increased
      the expression of hypoxia-inducible-factor-1alpha (HIF-1alpha) and induced the
      activation of the AKT/PKB kinase pathway, as shown by the increase of P(Ser-9)
      GSK-3beta, the inactive form of glycogen synthase kinase-3beta (GSK-3beta).
      Intriguingly, by the end of the fourth week the expression of tyrosine
      hydroxylase (TH) protein, a marker of dopaminergic neurons, was lower in nickel
      treated than in control cultures. Thus, likely by partially mimicking hypoxic
      conditions, a not-cytotoxic nickel concentration appears to alter the process of
      neuronal differentiation and hinder the expression of the dopaminergic neuronal
      phenotype. Taken together, these results suggest that nickel, by altering normal
      brain development, may increase susceptibility to neuro-psychopathology later in
      life. 

PMID- 25614231
TI  - Repeated exposure to chlorpyrifos leads to prolonged impairments of axonal
      transport in the living rodent brain.
AB  - The toxicity of the class of chemicals known as the organophosphates (OP) is most
      commonly attributed to the inhibition of the enzyme acetylcholinesterase.
      However, there is significant evidence that this mechanism may not account for
      all of the deleterious neurologic and neurobehavioral symptoms of OP exposure,
      especially those associated with levels that produce no overt signs of acute
      toxicity. In the study described here we evaluated the effects of the commonly
      used OP-pesticide, chlorpyrifos (CPF) on axonal transport in the brains of living
      rats using manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) of the
      optic nerve (ON) projections from the retina to the superior colliculus (SC). T1
      weighted MEMRI scans were evaluated at 6 and 24h after intravitreal injection of
      Mn(2+). As a positive control for axonal transport deficits, initial studies were
      conducted with the tropolone alkaloid colchicine administered by intravitreal
      injection. In subsequent studies both single and repeated exposures to CPF were
      evaluated for effects on axonal transport using MEMRI. As expected, intravitreal
      injection of colchicine (2.5MUg) produced a robust decrease in transport of
      Mn(2+) along the optic nerve (ON) and to the superior colliculus (SC) (as
      indicated by the reduced MEMRI contrast). A single subcutaneous (s.c.) injection
      of CPF (18.0mg/kg) was not associated with significant alterations in the
      transport of Mn(2+). Conversely, 14-days of repeated s.c. exposure to CPF
      (18.0mg/kg/day) was associated with decreased transport of Mn(2+) along the ONs
      and to the SC, an effect that was also present after a 30-day (CPF-free) washout
      period. These results indicate that repeated exposures to a commonly used
      pesticide, CPF can result in persistent alterations in axonal transport in the
      living mammalian brain. Given the fundamental importance of axonal transport to
      neuronal function, these observations may (at least in part) explain some of the
      long term neurological deficits that have been observed in humans who have been
      repeatedly exposed to doses of OPs not associated with acute toxicity. 

PMID- 25614232
TI  - Distribution, mass load and environmental impact of multiple-class
      pharmaceuticals in conventional and upgraded municipal wastewater treatment
      plants in East China.
AB  - The occurrence, fate and environmental impact of 30 pharmaceuticals including
      sulfonamides, fluoroquinolones, tetracyclines, macrolides, dihydrofolate
      reductase inhibitors, beta-blockers, antiepileptics, lipid regulators, and
      stimulants were studied in two municipal wastewater treatment plants (WWTPs)
      located in Wuxi City, East China. A total of 23 pharmaceuticals were detected in
      wastewater samples, with a maximum concentration of 16.1 MUg L(-1) (caffeine) in
      the influent and 615.5 ng L(-1) (azithromycin) in the effluent; 19
      pharmaceuticals were detected in sludge samples at concentrations up to 12.13 mg
      kg(-1), with ofloxacin, azithromycin and norfloxacin being the predominant
      species. Mass balance analysis showed that biodegradation primarily accounted for
      the removal of sulfonamides, most of the macrolides, and other miscellaneous
      pharmaceuticals, while adsorption onto the sludge was the primary removal pathway
      for fluoroquinolones, tetracylines, and azithromycin during biological treatment.
      The total mass loads of target pharmaceuticals per capita in the two WWTPs were
      in the ranges of 2681.8-4333.3, 248.0-416.6 and 214.6-374.5 MUg per day per
      inhabitant in the influent, effluent and dewatered sludge, respectively. The
      upgraded Plant A adopting the combined anaerobic/anoxic/oxic and moving bed
      biofilm process exhibited a much higher removal of target pharmaceuticals than
      the conventional Plant B adopting the C-Orbal oxidation ditch process. The
      concentration levels of sulfamethoxazole, ofloxacin, ciprofloxacin and
      clarithromycin in the effluent, ofloxacin in the sludge, and the mixture of all
      target pharmaceuticals in both effluent and sludge posed a high risk to algae in
      aquatic environments. 

PMID- 25614234
TI  - Revisiting the cortical system for peripheral reaching at the parieto-occipital
      junction.
AB  - Optic ataxia (OA) is a neurological disorder that is characterised by misreaching
      to targets in the visual periphery. The anatomy of OA thus provides important
      information for the neural representation of visually guided reaching in humans.
      In 2005 a lesion mapping analysis of OA localised the critical lesion site at the
      parieto-occipital junction (POJ) (Karnath & Perenin, 2005). This work was
      accompanied by the discovery of a peripheral reaching module at the POJ in an
      fMRI study (Prado et al., 2005). The ostensible overlap between the territory
      typically affected in patients with OA and the findings of Prado et al. (2005)
      had a tremendous influence on the search for a cortical peripheral reaching
      module. However, a close inspection of the functional Magnetic Resonance Imaging
      (fMRI) study revealed that a comparison between reaching towards visible targets
      in the peripheral visual field and reaching to visible targets in the central
      visual field--which is the key aspect in clinical examinations of OA--was not
      conducted. Moreover, whereas main effects of reaching overlapped with the OA
      lesion site, specific interaction effects did not overlap. We performed a direct
      comparison between reaching to visible peripheral targets and reaching to visible
      central targets to address the inconsistencies between the aforementioned
      studies. Our analysis shows that Prado et al.'s study cannot be taken as evidence
      for a delineated module for peripheral reaching. In contrast to Prado et al. we
      found a combined system of POJ, IPS and SPL areas--the posterior human 7A, mIPS,
      V6A and the posterior IPS--with increased signals during reaching to peripheral
      targets.

PMID- 25614233
TI  - Evidence for reduced efficiency and successful compensation in older adults
      during task switching.
AB  - Older adults often show different functional activation patterns than younger
      adults in prefrontal cortex (PFC) when performing cognitive control tasks. These
      differences include age-related increases in PFC activation magnitude and
      reorganized PFC functional connectivity (fC) patterns. However, it remains
      unclear whether age-related alterations in brain activation patterns reflect a
      positive mechanism (e.g., compensatory response) or a sign of brain dysfunction
      (e.g., reduced efficiency). Here we used functional magnetic resonance imaging
      (fMRI) to compare PFC activation magnitudes and PFC connectivity patterns between
      younger and older adult groups during performance of a task switching paradigm.
      Results indicated age-related increases both in PFC activation magnitudes and in
      PFC fC with inferotemporal (IT) regions. However, these age-related fMRI
      increases were differentially associated with task performance. Whereas increased
      PFC activation magnitudes tended to be either unrelated to task RT or associated
      with poorer task performance, increased PFC-IT connectivity was associated with
      better task performance in older adults. Our results suggest that age-related
      reductions in efficiency and successful compensation can co-exist in older adults
      in the context of the same task. 

PMID- 25614235
TI  - Germ line knockout of IGFBP-3 reveals influences of the gene on mammary gland
      neoplasia.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is an important carrier
      protein for insulin-like growth factors (IGFs) in the circulation. IGFBP-3
      antagonizes the growth-promoting and anti-apoptotic activities of IGFs in
      experimental systems, but in certain contexts can increase IGF bioactivity,
      probably by increasing its half-life. The goal of this study was to investigate
      the role of IGFBP-3 in breast carcinogenesis and breast cancer metastasis. In the
      first part of the study, we exposed IGFBP-3 knockout and wild-type female mice to
      dimethylbenz[a]anthracene (DMBA) and followed them for appearance of primary
      tumors for up to 13 months. In the second part, mice of each genotype received an
      IV injection of 4T1 mammary carcinoma cells and then lung nodules were counted.
      Our results show that IGFBP-3 knockout mice developed breast tumors significantly
      earlier than the wild-type (13.9 +/- 1.1 versus 22.5 +/- 3.3 weeks, respectively,
      P = 0.0144), suggesting tumor suppression activity of IGFBP-3. In tumors of IGFBP
      3 knockout mice, levels of phospho-AKT(Ser473) were increased compared to wild
      type mice. The lung metastasis assay showed significantly more and larger lung
      nodules in IGFBP-3 knockout mice than in wild-type mice. While we observed
      increased levels of IGFBP-5 protein in the IGFBP-3 knockout mice, our findings
      suggest that this was not sufficient to completely compensate for the absence of
      IGFBP-3. Even though knockout of IGFBP-3 is associated with only a subtle
      phenotype under control conditions, our results reveal that loss of this gene has
      measurable effects on breast carcinogenesis and breast cancer metastasis.

PMID- 25614236
TI  - The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls
      Caenorhabditis elegans Q neuroblast polarization during migration.
AB  - Directional cell migration is fundamental for neural development, and
      extracellular factors are pivotal for this process. Heparan sulfate proteoglycans
      (HSPGs) that carry long chains of differentially modified sugar residues
      contribute to extracellular matrix; however, the functions of HSPG in guiding
      cell migration remain elusive. Here, we used the Caenorhabditis elegans mutant
      pool from the Million Mutation Project and isolated a mutant allele of the
      heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5. Loss-of-function
      of this enzyme resulted in defective Q neuroblast migration. We showed that hse-5
      controlled Q cell migration in a cell non-autonomous manner. By performing live
      cell imaging in hse-5 mutant animals, we found that hse-5 controlled initial
      polarization during Q neuroblast migration. Furthermore, our genetic epistasis
      analysis demonstrated that lon-2 might act downstream of hse-5. Finally, rescue
      of the hse-5 mutant phenotype by expression of human and mouse hse-5 homologs
      suggested a conserved function for this gene in neural development. Taken
      together, our results indicated that proper HSPG modification in the
      extracellular matrix by HSE-5 is essential for neuroblast polarity during
      migration. 

PMID- 25614237
TI  - Loss of function of the yellow-e gene causes dehydration-induced mortality of
      adult Tribolium castaneum.
AB  - Yellow protein (dopachrome conversion enzyme, DCE) is involved in the melanin
      biosynthetic pathway that significantly accelerates pigmentation reactions in
      insects. Recent studies have suggested that the insect yellow genes represent a
      rapidly evolving gene family generating functionally diverse paralogs, but the
      exact physiological functions of several yellow genes are still not understood.
      To study the function(s) of one of the yellow genes, yellow-e (TcY-e), in the red
      flour beetle, Tribolium castaneum, we performed real-time PCR to analyze its
      developmental and tissue-specific expression, and utilized immunohistochemistry
      to identify the localization of the TcY-e protein in adult cuticle. Injection of
      double-stranded RNA for TcY-e (dsTcY-e) into late instar larvae had no effect on
      larval-pupal molting or pupal development. The pupal cuticle, including that
      lining the setae, gin traps and urogomphi, underwent normal tanning. Adult
      cuticle tanning including that of the head, mandibles and legs viewed through the
      translucent pupal cuticle was initiated on schedule (pupal days 4-5), indicating
      that TcY-e is not required for pupal or pharate adult cuticle pigmentation in T.
      castaneum. The subsequent pupal-adult molt, however, was adversely affected.
      Although pupal cuticle apolysis and slippage were evident, some of the adults
      (~25%) were unable to shed their exuvium and died entrapped in their pupal
      cuticle. In addition, the resulting adults rapidly became highly desiccated.
      Interestingly, both the failure of the pupal-adult molt and desiccation-induced
      mortality were prevented by maintaining the dsTcY-e-treated insects at 100%
      relative humidity (rh). However, when the high humidity-rescued adults were
      removed from 100% rh and transferred to 50% rh, they rapidly dehydrated and died,
      whereas untreated beetles thrived throughout development at 50% rh. We also
      observed that the body color of the high humidity-rescued dsTcY-e-adults was
      slightly darker than that of control animals. These results support the
      hypothesis that TcY-e has a role not only in normal body pigmentation in T.
      castaneum adults but also has a vital waterproofing function. 

PMID- 25614239
TI  - Co-expression of the transcription factors CEH-14 and TTX-1 regulates AFD neuron
      specific genes gcy-8 and gcy-18 in C. elegans.
AB  - A wide variety of cells are generated by the expression of characteristic sets of
      genes, primarily those regulated by cell-specific transcription. To elucidate the
      mechanism regulating cell-specific gene expression in a highly specialized cell,
      AFD thermosensory neuron in Caenorhabditis elegans, we analyzed the promoter
      sequences of guanylyl cyclase genes, gcy-8 and gcy-18, exclusively expressed in
      AFD. In this study, we showed that AFD-specific expression of gcy-8 and gcy-18
      requires the co-expression of homeodomain proteins, CEH-14/LHX3 and TTX-1/OTX1.
      We observed that mutation of ttx-1 or ceh-14 caused a reduction in the expression
      of gcy-8 and gcy-18 and that the expression was completely lost in double
      mutants. This synergy effect was also observed with other AFD marker genes, such
      as ntc-1, nlp-21and cng-3. Electrophoretic mobility shift assays revealed direct
      interaction of CEH-14 and TTX-1 proteins with gcy-8 and gcy-18 promoters in
      vitro. The binding sites of CEH-14 and TTX-1 proteins were confirmed to be
      essential for AFD-specific expression of gcy-8 and gcy-18 in vivo. We also
      demonstrated that forced expression of CEH-14 and TTX-1 in AWB chemosensory
      neurons induced ectopic expression of gcy-8 and gcy-18 reporters in this neuron.
      Finally, we showed that the regulation of gcy-8 and gcy-18 expression by ceh-14
      and ttx-1 is evolutionally conserved in five Caenorhabditis species. Taken
      together, ceh-14 and ttx-1 expression determines the fate of AFD as terminal
      selector genes at the final step of cell specification. 

PMID- 25614238
TI  - microRNAs regulate beta-catenin of the Wnt signaling pathway in early sea urchin
      development.
AB  - Development of complex multicellular organisms requires careful regulation at
      both transcriptional and post-transcriptional levels. Post-transcriptional gene
      regulation is in part mediated by a class of non-coding RNAs of 21-25 nucleotides
      in length known as microRNAs (miRNAs). beta-catenin, regulated by the canonical
      Wnt signaling pathway, has a highly evolutionarily conserved function in
      patterning early metazoan embryos, in forming the Anterior-Posterior axis, and in
      establishing the endomesoderm. Using reporter constructs and site-directed
      mutagenesis, we identified at least three miRNA binding sites within the 3'
      untranslated region (3'UTR) of the sea urchin beta-catenin. Further, blocking
      these three miRNA binding sites within the beta-catenin 3'UTR to prevent
      regulation of endogenous beta-catenin by miRNAs resulted in a minor increase in
      beta-catenin protein accumulation that is sufficient to induce aberrant gut
      morphology and circumesophageal musculature. These phenotypes are likely the
      result of increased transcript levels of Wnt responsive endomesodermal regulatory
      genes. This study demonstrates the importance of miRNA regulation of beta-catenin
      in early development. 

PMID- 25614240
TI  - Diurnal and stress-induced intra-hippocampal corticosterone rise attenuated in
      11beta-HSD1-deficient mice: a microdialysis study in young and aged mice.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates
      active glucocorticoids from their inert forms thereby amplifying intracellular
      levels within target tissues including the brain. We previously showed greater
      increases in intra-hippocampal corticosterone (CORT) levels upon Y-maze testing
      in aged wild-type than in 11beta-HSD1(-/-) mice coinciding with impaired and
      intact spatial memory, respectively. Here we examined whether ageing influences
      11beta-HSD1 regulation of CORT in the dorsal hippocampus under basal conditions
      during the diurnal cycle and following stress. Intra-hippocampal CORT levels
      measured by in vivo microdialysis in freely behaving wild-type mice displayed a
      diurnal variation with peak levels in the evening that were significantly
      elevated with ageing. In contrast, the diurnal rise in intra-hippocampal CORT
      levels was greatly diminished in 11beta-HSD1(-/-) mice and there was no rise with
      ageing; basal intra-hippocampal CORT levels were similar to wild-type controls.
      Furthermore, a short (3 min) swim stress induced a longer lasting increase in
      intra-hippocampal CORT levels in wild-type mice than in 11beta-HSD1(-/-) mice
      despite no genotypic differences in elevation of plasma CORT. These data indicate
      that 11beta-HSD1 activity contributes substantially to diurnal and stress-induced
      increases in hippocampal CORT levels. This contribution is even greater with
      ageing. Thus, 11beta-HSD1 inhibition may be an attractive target for treating
      cognitive impairments associated with stress or ageing. 

PMID- 25614241
TI  - A categorical approach to infants' individual differences during the Still-Face
      paradigm.
AB  - Cluster analysis was used to create patterns of individual differences reflecting
      infant behaviors during the initial interaction episode of the Face-to-Face Still
      Face (FFSF) paradigm. The clusters were used as the basic unit of analysis for
      studying infant and maternal behavior and dyadic coordination (i.e., matching and
      reparation) across FFSF. Seventy-five 4-month-old infants participated with their
      mothers. Cluster analysis identified three patterns: a Socially Engaged cluster
      (33%) exhibited high levels of social engagement with their mothers; a Disengaged
      cluster (60%) showed a tendency to be low in social interaction and a Negatively
      Engaged cluster (7%) showed high negative emotionality. During the Still-Face
      episode, the Socially Engaged cluster reacted by reducing focus on their mother
      and shifting their attention elsewhere, while infants in the Disengaged cluster
      reduced focus on the environment. Although both the Socially Engaged and
      Disengaged clusters increased in negative emotionality during the Still-Face, the
      Socially Engaged group largely recovered during the Reunion, whereas the
      Disengaged group displayed more negative emotion. The Negatively Engaged cluster
      demonstrated high levels of negative affect throughout the entire procedure.
      Mothers of Negatively Engaged infants showed less positive engagement and more
      social monitoring than mothers in other clusters during all episodes. Dyadic
      interaction differed between groups, with greater levels of matching and
      reparations in the engaged group, less in the Disengaged group, and very little
      coordination in the Negatively Engaged cluster. Findings highlight the role of
      distinctive patterns of infants' individual differences in determining early
      dyadic functioning. 

PMID- 25614242
TI  - Combining porphyrins and pH indicators for analyte detection.
AB  - High sensitivity and cross-selectivity are mandatory properties for sensor
      arrays. Although metalloporphyrins and pH indicators are among the most common
      and appropriate choices for the preparation of optical sensor arrays, the
      sensitivity spectrum of these dyes is limited to those analytes able to induce an
      optical response. To extend the receptive field of optical sensors, we explore
      the design of composite materials, where the molecular interaction among the
      subunits enriches their sensing working mechanisms. We demonstrate that blends of
      single metalloporphyrins and pH indicators, tested with a transduction apparatus
      based on ubiquitous and easily available hardware, can be endowed with sensing
      properties wider than those of single constituents, enabling the recognition of a
      broad range of volatiles. 

PMID- 25614243
TI  - Therapeutic antibodies against CGRP or its receptor.
AB  - CGRP is an extensively studied neuropeptide that has been implicated in the
      pathophysiology of migraine. While a number of small molecule antagonists against
      the CGRP receptor have demonstrated that targeting this pathway is a valid and
      effective way of treating migraine, off-target hepatoxicity and formulation
      issues have hampered the development for regulatory approval of any therapeutic
      in this class. The development of monoclonal antibodies to CGRP or its receptor
      as therapeutic agents has allowed this pathway to be re-investigated. Herein we
      review why CGRP is an ideal target for the prevention of migraine and describe
      four monoclonal antibodies against either CGRP or its receptor that are in
      clinical development for the treatment of both episodic and chronic migraine. We
      describe what has been publically disclosed about their clinical trials and
      future clinical development plans.

PMID- 25614245
TI  - Production of 3-hydroxypropionic acid from 3-hydroxypropionaldehyde by
      recombinant Escherichia coli co-expressing Lactobacillus reuteri propanediol
      utilization enzymes.
AB  - 3-Hydroxypropionic acid (3-HP) is an important platform chemical for the biobased
      chemical industry. Lactobacillus reuteri produces 3-HP from glycerol via 3
      hydroxypropionaldehyde (3-HPA) through a CoA-dependent propanediol utilization
      (Pdu) pathway. This study was performed to verify and evaluate the pathway
      comprising propionaldehyde dehydrogenase (PduP), phosphotransacylase (PduL), and
      propionate kinase (PduW) for formation of 3-HP from 3-HPA. The pathway was
      confirmed using recombinant Escherichia coli co-expressing PduP, PduL and PduW of
      L. reuteri DSM 20016 and mutants lacking expression of either enzyme. Growing and
      resting cells of the recombinant strain produced 3-HP with a yield of 0.3mol/mol
      and 1mol/mol, respectively, from 3-HPA. 3-HP was the sole product with resting
      cells, while growing cells produced 1,3-propanediol as co-product. 3-HP
      production from glycerol was achieved with a yield of 0.68mol/mol by feeding
      recombinant E. coli with 3-HPA produced by L. reuteri and recovered using
      bisulfite-functionalized resin. 

PMID- 25614246
TI  - Effects of mesostructured silica catalysts on the depolymerization of organosolv
      lignin fractionated from woody eucalyptus.
AB  - Isolated and purified organosolv eucalyptus wood lignin was depolymerized at
      different temperatures with and without mesostructured silica catalysts (i.e.,
      SBA-15, MCM-41, ZrO2-SBA-15 and ZrO2-MCM-41). It was found that at 300 degrees C
      for 1h with a solid/liquid ratio of 0.0175/1 (w/v), the SBA-15 catalyst with high
      acidity gave the highest syringol yield of 23.0% in a methanol/water mixture
      (50/50, wt/wt). Doping with ZrO2 over these catalysts did not increase syringol
      yield, but increased the total amount of solid residue. Gas chromatography-mass
      spectrometry (GC-MS) also identified other main phenolic compounds such as 1-(4
      hydroxy-3,5-dimethoxyphenyl)-ethanone, 1,2-benzenediol, and 4-hydroxy-3,5
      dimethoxy-benzaldehyde. Analysis of the lignin residues with Fourier transform
      infrared spectroscopy (FT-IR) indicated decreases in the absorption bands
      intensities of OH group, CO stretching of syringyl ring and aromatic CH
      deformation of syringol unit, and an increase in band intensities associated with
      the guaiacyl ring, confirming the type of products formed. 

PMID- 25614244
TI  - Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof
      from a meta-analysis.
AB  - Phospholipase C epsilon 1 (PLCE1) plays an important role in cell growth,
      differentiation and oncogenesis. An increasing number of individual studies have
      investigated the association between PLCE1 rs2274223 polymorphism and cancer
      risk, but the conclusions are inconclusive. To obtain a comprehensive conclusion,
      we performed a meta-analysis of 22 studies with 13188 cases and 14666 controls.
      The pooled results indicated that PLCE1 rs2274223 A > G polymorphism was
      associated with an increased risk of overall cancer (G vs. A: OR = 1.15, 95% CI =
      1.06-1.25; GG vs. AA: OR = 1.30, 95% CI = 1.10-1.55; GA vs. AA: OR = 1.18, 95% CI
      = 1.08-1.30; GG/GA vs. AA: OR = 1.20, 95% CI = 1.08-1.32; GG vs. GA/AA: OR =
      1.22, 95% CI = 1.04-1.42). The stratification analysis showed the polymorphism
      was significantly associated with an increased risk of esophageal squamous cell
      carcinoma (ESCC) other than gastric cancer (GC), especially among the subgroups
      of Asian, high quality score, sample size > 1000 and the studies consistent with
      Hardy-Weinberg equilibrium (HWE). This meta-analysis demonstrated that PLCE1
      rs2274223 A > G polymorphism may be associated with increased susceptibility to
      cancer, especially for ESCC. However, due to the substantial heterogeneities
      across the studies, the conclusion might be not conclusive that need more studies
      to confirm.

PMID- 25614247
TI  - Laser ablation of posterior urethral valves by fetal cystoscopy.
AB  - OBJECTIVE: To report the results of fetal cystoscopic laser ablation of posterior
      urethral valves (PUV) in a consecutive series in two referral centers. METHODS:
      Twenty pregnant women with a presumptive isolated PUV were treated with fetal
      cystoscopy under local anesthesia. Identification and fulguration of the PUV by
      one or several firing-contacts with diode laser were attempted. Perinatal and
      long-term outcomes were prospectively recorded. RESULTS: The median gestational
      age at procedure was 18.1 weeks (range 15.0-25.6), and median operation time was
      24 min (range 15-40). Access to the urethra was achieved in 19/20 (95%) cases,
      and postoperative, normalization of bladder size and amniotic fluid was observed
      in 16/20 (80%). Overall, there were 9 (45%) terminations of pregnancy and 11
      women (55%) delivered a liveborn baby at a mean gestational age of 37.3 (29.1
      40.2) weeks. No infants developed pulmonary hypoplasia and all were alive at 15
      110 months. Eight (40% of all fetuses, 72.7% of newborns) had normal renal
      function and 3 (27.3%) had renal failure awaiting renal transplantation.
      CONCLUSION: Fetoscopic laser ablation for PUV can achieve bladder decompression
      and amniotic fluid normalization with a single procedure in selected cases with
      anyhydramnios. There is still a significant risk of progression to renal failure
      pre or postnatally.

PMID- 25614248
TI  - Risk factors and causes of sudden noncardiac death: A nationwide cohort study in
      Denmark.
AB  - BACKGROUND: On the performance of an autopsy, sudden deaths may be divided into 2
      classifications: (1) sudden cardiac deaths and (2) sudden noncardiac deaths
      (SNCDs). Families of SNCD victims should not be followed up as a means of
      searching for cardiac disease. OBJECTIVE: The purpose of this study was to report
      the risk factors and causes of SNCD. METHODS: We conducted a retrospective,
      nationwide study including all deaths between 2000 and 2006 of individuals aged 1
      35 years and all deaths between 2007 and 2009 of individuals aged 1-49 years. Two
      physicians identified all sudden death cases through review of death
      certificates. Autopsy reports were collected. A multivariable logistic regression
      model was used to identify both clinical characteristics and risk factors
      associated with SNCD. RESULTS: We identified 1039 autopsied cases of sudden
      death, of which 286 (28%) were classified as SNCD. The median age in the SNCD
      death population was 32 years. Increasing age was inversely associated with SNCD
      (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.87-0.98). Female sex, in
      hospital location, and the absence of cardiac comorbidities were positively
      associated with SNCD (OR 1.7, 95% CI 1.3-2.3; OR 3.0, 95% CI 2.0-4.4; and OR 4.3,
      95% CI 2.5-7.4, respectively). The most common cause of SNCD was pulmonary
      disease (n = 115 [40%]). CONCLUSION: Sudden death among individuals aged <50
      years was caused by noncardiac diseases in 28% of cases. Risk factors were female
      sex, age, and the absence of cardiac comorbidities. These data may guide future
      strategies for the follow-up of family members of nonautopsied sudden death
      victims, improve risk stratification, and influence public health strategies.

PMID- 25614249
TI  - Glycated hemoglobin and risk of first episode stroke in diabetic patients with
      atrial fibrillation: A cohort study.
AB  - BACKGROUND: Diabetes is associated with an increased risk of stroke in patients
      with atrial fibrillation. Whether glycemic control, evaluated by glycated
      hemoglobin, affects the risk of stroke in diabetic patients with atrial
      fibrillation remains unknown. OBJECTIVE: To examine the association between
      glycated hemoglobin and risk of first episode stroke in diabetic patients with
      atrial fibrillation. METHODS: By using the computerized database of the largest
      health maintenance organization in Israel, we identified a cohort of adults (age
      >=20 years) in whom atrial fibrillation was diagnosed before January 1, 2012.
      Eligible subjects had no previous stroke or transient ischemic attack and were
      not on anticoagulants at baseline. The cohort (37,358 subjects) was followed for
      the first episode stroke or transient ischemic attack up to December 31, 2012.
      RESULTS: A total of 1052 subjects had stroke during 35,278 person-years of follow
      up (stroke rate 2.98 per 100 person-years). Cox proportional hazards regression
      analysis adjusting for CHA2DS2-VASc score risk factors revealed that compared
      with subjects without diabetes, the hazard ratio for stroke was 1.04 (95%
      confidence interval [CI] 0.83-1.30) for the lowest glycated hemoglobin quartile
      (<6.35%), 1.14 (95% CI 0.92-1.42) for the second quartile (6.35%-6.90%), 1.46
      (95% CI 1.19-1.79) for the third quartile (>6.90%-7.70%), and 1.63 (95% CI 1.33
      2.00) for the highest quartile(>7.70%) (for trend, P < .001). In diabetic
      patients (n = 11,176), the hazard ratio for stroke was 1.17 (95% CI 1.09-1.26)
      for every 1% increment in glycated hemoglobin level. The area under the receiver
      operating characteristic curve was 0.585 for the CHA2DS2-VASc score, which
      increased to 0.604 when glycated hemoglobin was included in the model (P = .038).
      CONCLUSION: Glycated hemoglobin is directly associated with stroke risk, and it
      improves the predictive accuracy for stroke in diabetic patients with atrial
      fibrillation.

PMID- 25614250
TI  - Nonspecific intraventricular conduction delay: Definitions, prognosis, and
      implications for cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is an electrical treatment of heart
      failure with reduced ejection fraction and wide QRS. It aims to correct the
      electrical dyssynchrony present in 30% to 50% of patients in this population.
      Dyssynchrony results in widening of the QRS complex on the electrocardiogram
      (ECG). CRT was initially developed to treat patients who had left bundle branch
      block (LBBB) and delayed activation of the lateral left ventricular wall.
      However, a large proportion of heart failure patients present with a widened QRS
      that is neither an LBBB nor a right bundle branch block (RBBB): nonspecific
      intraventricular conduction delay (NICD). Less studied than RBBB or LBBB, its
      pathophysiology is both complex and varied yet still reflects intramyocardial
      conduction delay. NICD is most often associated with cardiomyopathy (eg, ischemic
      or hypertensive). Conduction pathways can be either healthy or affected. Results
      from CRT are contradictory in this patient group, despite a seemingly neutral
      trend. Unfortunately, prospective studies are lacking. Guidelines recommending
      implantation of CRT devices in this group are based solely on analyses of
      subgroups with small sample sizes. A dedicated prospective study is therefore
      warranted for this question to be answered properly. A detailed study of the ECG
      and noninvasive study of ventricular electrical activation may enable clinicians
      to better identify patients with NICD who will respond to CRT. 

PMID- 25614251
TI  - [E.G. Simon et al. in reply to the article by M. Constant: nuchal translucency:
      this is not so simple! Gynecol Obstet Fertil 2014;42:820-21].

PMID- 25614252
TI  - Effects of methionine supplementation on the expression of oxidative stress
      related genes in acute heat stress-exposed broilers.
AB  - The aim of the present study was to evaluate the effects of heat stress (HS) and
      methionine supplementation on the markers of stress and on the gene expression
      levels of uncoupling proteins (UCP), betaine-homocysteine methyltransferase
      (BHMT), cystathionine beta-synthase (CBS), glutathione synthetase (GSS) and
      glutathione peroxidase 7 (GPx7). Broilers from 1 to 21 d and from 22 to 42 d of
      age were divided into three treatment groups related to methionine
      supplementation: without methionine supplementation (MD); recommended level of
      methionine supplementation (DL1); excess methionine supplementation (DL2). The
      broilers were either kept at a comfortable thermal temperature or exposed to HS
      (38 degrees C for 24 h). During the starter period, we observed the effects of
      the interaction between diet and environment on the gene expression levels of
      UCP, BHMT and GSS. Higher gene expression levels of UCP and BHMT were observed in
      broilers that were maintained at thermal comfort conditions and received the MD
      diet. HS broilers fed the DL1 and DL2 diets had the highest expression level of
      GSS. The expression levels of the CBS and GPx7 genes were influenced by both the
      environment and methionine supplementation. During the grower period, the gene
      expression levels of BHMT, CBS, GSS and GPx7 were affected by the diet *
      environment interaction. A higher expression level of BHMT was observed in
      broilers maintained at thermal comfort conditions and on the MD diet. HS induced
      higher expression levels of CBS, GSS and GPx7 in broilers that received the DL1
      and DL2 diets. The present results suggest that under HS conditions, methionine
      supplementation could mitigate the effects of stress, since methionine
      contributed to the increased expression levels of genes related to antioxidant
      activity. 

PMID- 25614253
TI  - Ten-year outcomes of I125 low-dose-rate brachytherapy for clinically localized
      prostate cancer: a single-institution experience in Japan.
AB  - PURPOSE: To report 10-year outcomes of patients treated with I(125) low-dose-rate
      brachytherapy (BT) for clinically localized prostate cancer. METHODS: A group of
      1,060 patients with clinically localized prostate cancer treated with I(125) BT
      between March 2004 and December 2013 at the Yokohama City University Hospital
      were identified. The records of 743 patients with a minimum of 2 years of follow
      up were reviewed. Cohorts were categorized according to National Comprehensive
      Cancer Network risk classification, and biochemical outcomes plus overall
      survival were examined. Biochemical failure was defined as nadir prostate
      specific antigen (PSA) level + 2 ng/mL. Univariate and multivariate Cox
      proportional hazards were used to determine predictors of biochemical failure.
      RESULTS: A total of 743 patients met the criteria with a median follow-up of 54.6
      months (range 24-114 months). The median age was 70 years (range 48-83). The 5-
      and 7-year overall survival rates were 98.8 and 97.6 %, and the 5- and 7-year
      biochemical failure-free survival rates were 92.6 and 91.0 %, respectively. With
      regard to distant metastases and survival, the 5- and 7-year metastatic-free
      survival rates were 98.2 and 95.9 %, respectively. A multivariate analysis
      revealed that initial PSA (p = 0.005; HR 1.097, 95 % CI 1.028-1.170), age (p =
      0.001; HR 0.931, 95 % CI 0.893-0.971), and T stage (T1c vs. T2a) (p = 0.002;
      HR2.417, 95 % CI 1.319-4.267) were independent predictors of biochemical failure.
      CONCLUSIONS: I(125) low-dose-rate BT resulted in excellent survival and morbidity
      outcomes for localized prostate cancer at a single institution. Further studies
      are needed to obtain long-term outcomes.

PMID- 25614254
TI  - Flow matters 2: How to improve irrigation flow in small-calibre percutaneous
      procedures-the purging effect.
AB  - INTRODUCTION: Aim of this study was to investigate whether the combination of
      high-pressure irrigation inflow combined with simultaneous sensor-controlled
      suction could improve irrigation turnover without leading to high peak intrarenal
      pressure in small-calibre percutaneous instruments (SCPI). M + M: A MIP XS sheath
      (9.5 Fr. outer diameter and 8.5 Fr. inner diameter) and a 7.5-Fr. nephroscope (3
      Fr. irrigation channel; MIP XS by Nagele, Karl Storz, Tuttlingen, Germany) was
      inserted into the collecting system of a non-perfused cadaveric porcine kidney,
      an 8-Fr. mono-J catheter was introduced through the ureter. Irrigation was
      performed using a pressure-controlled, combined irrigation/suction pump (Uromat
      E.A.S.I., Karl Storz, Tuttlingen, Germany) in either single-flow or continuous
      flow (=combination of irrigation and suction) mode. Intrarenal pressure was
      measured and irrigation fluid turnover was measured by a cystometry catheter
      inserted trans-parenchymally into the renal pelvis. Pressure changes were
      recorded by a urodynamic workstation. RESULTS: Applying pressure-controlled
      suction, irrigation fluid turnover could be increased by 5 % at an inflow
      pressure of 75 mmHg (80-84 ml/min) and 15 % at an inflow pressure of 110 mmHg
      (196-110 ml/min). Suction decreased the intrarenal pressure by 14 % at 75 mmHg
      (19-14.5 cm H2O) and 28 % at 110 mmHg inflow pressure (37-26.5 cm H2O).
      CONCLUSION: Although combination of pressure irrigation with sensor-controlled
      suction increases irrigation flow in SCPI, the intrarenal pressure could be
      reduced with combined suction via a transurethral mono-J catheter. This
      irrigation method in percutaneous surgery is called purging effect.

PMID- 25614255
TI  - Ultra-mini PCNL versus flexible ureteroscopy: a matched analysis of treatment
      costs (endoscopes and disposables) in patients with renal stones 10-20 mm.
AB  - PURPOSE: Latest publications state equal efficacy of a recently introduced new
      percutaneous technique ("ultra-mini PCNL", UMP) and flexible ureteroscopy (fURS)
      in the treatment of medium-size urinary stones. Today we face challenges
      concerning cost-effectiveness and reduction of in-hospital length of stay. In
      this retrospective study, we compare clinical outcome parameters and costs of
      treatment (endoscopes and disposables) of both techniques. METHODS: Thirty
      patients treated by UMP at two tertiary university centres were matched to 30
      fURS patients from previously recorded databases. Data analysis included
      operating time, length of stay, stone-free rates (SFR), complications (>Clavien
      II), ancillary procedures (presurgical ureteral stenting, secondary ureteral
      stenting or placement of a nephrostomy tube, secondary procedures) and costs for
      disposable materials and instruments (endoscopes, as calculated per procedure).
      RESULTS: We found no significant differences in operating times (UMP vs. fURS:
      121/102 min), hospital length of stay (2.3/2.0 days), SFR (84/87 %) and
      complications (7/7 %). Costs for disposable materials and endoscopes were 656
      euro (UMP) and 1,160 euro (fURS) per procedure. CONCLUSIONS: UMP and fURS are
      both safe and effective in the treatment of medium-size urinary stones. Costs for
      endoscopes and disposable materials are significantly lower in UMP.

PMID- 25614256
TI  - Feasibility, safety, and efficacy of salvage radical prostatectomy after
      Tookad(r) Soluble focal treatment for localized prostate cancer.
AB  - PURPOSE: To investigate feasibility, safety, and efficacy of salvage radical
      prostatectomy (RP) for recurrent prostate cancer (PCa) after focal treatment with
      TOOKAD((r)) Soluble vascular-targeted photodynamic therapy (VTP). METHODS:
      Nineteen patients underwent RP after biopsy-proven PCa post-focal VTP. We
      reported: operation time, blood loss, transfusion, complications, urethral
      catheterization time, functional outcomes, and short-term oncologic outcomes.
      RESULTS: Median age was 64 years (58-70). Median PSA before VTP was 6.30 ng/ml
      (3.20-9.80). Median delay between VTP and RP was 17 months (8-48). Median blood
      loss was 400 ml (100-1,000). Median operation time was 150 min (90-210), median
      urethral catheterization time was 7 days (5-18), and median hospital stay was 7
      days (4-21). There was no perioperative mortality. Three patients had related per
      operative complications: one pelvic hematoma (150 cc) (Clavien IIIa), one per
      operative transfusion (900 cc hemorrhage) (Clavien II), and one superficial wound
      infection (Clavien I). After a median follow-up of 10 months (1-46), 13 were
      completely continent (68 %), five needed <=1 pad/day, and one needed 3 pads/day
      (Clavien I). Severe erectile dysfunction was observed before and after RP
      (respectively 8 and 18). Ten patients regained potency with appropriate
      treatment. Median postoperative PSA was 0.02 ng/ml (<0.01-0.38) and remained
      undetectable for 16 patients (84 %). Nine patients had positive margins and six
      underwent complementary radiotherapy. Positive margins were significantly
      associated with bilateral VTP [risk ratio = 4.3, 95 % confidence interval (1.6
      11.7), p = 0.003]. CONCLUSION: Salvage RP after VTP treatment was feasible, safe,
      and efficient to treat most of the locally recurrent PCa. Short-term oncologic
      and functional outcomes were promising, but further studies are required.

PMID- 25614258
TI  - Electric-acoustic stimulation: for whom, in which ear, and how.

PMID- 25614259
TI  - Achievement of early clinical milestones and long-term functional outcomes for
      children and young adults with bilateral cochlear implants.

PMID- 25614260
TI  - Performance ratings for children using bilateral cochlear implants obtained with
      the speech, spatial, and other qualities of hearing scale for parents.

PMID- 25614261
TI  - Paediatric unilateral implantation in an era of routine simultaneous bilateral
      implantation.

PMID- 25614262
TI  - Preschool television programmes: analysis using SmartSound IQ data logging.

PMID- 25614263
TI  - An aging concern: A retrospective study comparing the audiological and speech
      outcome measures along with the surgical and quality-of-life outcomes in a group
      of geriatric patients with those of an adult control group.

PMID- 25614264
TI  - The use of functional near-infrared spectroscopy for measuring cortical
      reorganisation in cochlear implant users: a possible predictor of variable speech
      outcomes?

PMID- 25614265
TI  - Straight vs. modiolar hugging electrodes--does one perform better than the other?

PMID- 25614266
TI  - Patient satisfaction survey of the same day assessment for adult cochlear implant
      candidates.

PMID- 25614267
TI  - The role of the immune system in hearing preservation after cochlear
      implantation.

PMID- 25614268
TI  - CI outcomes in children: are the NICE guidelines appropriate for adults?

PMID- 25614269
TI  - Candidacy criteria for paediatric bilateral cochlear implantation in the United
      Kingdom.

PMID- 25614270
TI  - Tough choices: The challenges of cochlear implantation when there is 'something
      to lose'.

PMID- 25614271
TI  - The missing link in language learning of children who are deaf or hard of
      hearing: pragmatics.

PMID- 25614272
TI  - Paediatric vestibulo-cochlear malformations and international collaboration for
      the U.K.'s first bilateral FORM19 electrode cochlear implantation.

PMID- 25614273
TI  - Balancing cochlear implant AGC and near-instantaneous compression to improve
      perception of soft speech.

PMID- 25614274
TI  - Denosumab for the treatment of osteoporosis.
AB  - INTRODUCTION: Low trauma fractures due to osteoporosis are a major health concern
      worldwide. Despite the availability of many therapeutic compounds to reduce
      fracture risk, osteoporosis remains undertreated and the burden of osteoporotic
      fractures remains high. Denosumab is a novel agent that acts to reduce bone
      turnover, improve bone mineral density, and reduce fracture risk, offering a
      favorable efficacy and safety profile. AREAS COVERED: This review covers the
      pharmacology and major clinical trials with extension/post-marketing follow-up,
      including trials for all FDA-approved indications of denosumab to date. EXPERT
      OPINION: Denosumab is an efficacious and safe osteoporosis treatment option, with
      current data from up to 8 years of continued use showing continued improvement in
      bone density with sustained fracture risk reduction. Safety profiles overall are
      similar to placebo, with no new safety concerns in extension trials, though a
      theoretical increased risk of infection exists with RANKL inhibition. Future
      considerations include safety of prolonged treatment beyond 8 years, and
      efficacy/fracture risk after discontinuation or with non-adherence, given the
      characteristic pharmacodynamic profile of denosumab.

PMID- 25614275
TI  - Reverse-dipper pattern of blood pressure may predict lacunar infarction in
      patients with essential hypertension.
AB  - BACKGROUND AND PURPOSE: The fluctuation of circadian blood pressure (BP) is of
      great diversity in patients with essential hypertension and may provide
      significant prognostic value for stroke. However, it remains uncertain whether
      reverse-dipper pattern of BP influences the incidence of lacunar infarction in
      hypertensive patients. METHODS: In the current study, 362 hypertensive patients
      (195 males, 167 females) were enrolled. BP patterns were evaluated with 24-h
      ambulatory BP monitoring (ABPM). Multinomial logistic regression was applied to
      analyse the possible relationships between lacunar infarction and various
      clinical risk factors such as ABPM. RESULTS: A total of 93 patients (25.7%) had
      reverse-dipper BP pattern. Non-dipper pattern of BP was observed in 179
      hypertensive patients (49.4%) and dipper pattern in 90 patients (24.9%). The
      percentage of lacunar infarction was the highest in the patients with reverse
      dipper pattern compared with pure hypertension or atherothrombotic cerebral
      infarction (P < 0.05). After multinomial logistic regression analysis, reverse
      dipper pattern of BP (odds ratio 2.492; 95% confidence interval 1.133-5.479; P <
      0.05) and age (odds ratio 1.084; 95% confidence interval 1.047-1.123; P < 0.01)
      were found to be directly associated with lacunar infarction. CONCLUSIONS:
      Reverse-dipper BP pattern may serve as an independent risk factor for lacunar
      infarction and more personalized BP management should be offered to the patients
      who have elevated nocturnal BP.

PMID- 25614276
TI  - The role of social support in the acculturation and mental health of
      unaccompanied minor asylum seekers.
AB  - There is a lack of knowledge about psychosocial resources that may sustain post
      resettlement psychological adjustment among unaccompanied minor asylum-seekers.
      The aim of this study is to investigate the impact of social support from family
      abroad and friends on acculturation, discrimination, and mental health among
      these vulnerable children and youth. Questionnaire data were collected from a
      population-based multi-ethnic sample involving 895 unaccompanied minors resettled
      in municipalities in all regions of the country. They met in groups in their
      local communities. The informants were on average 18.6 years, and had an average
      length of stay in Norway of 3.5 years. The findings showed that the participants
      suffered from high levels of ongoing war related intrusive symptoms and
      depression. Still, at the same time they engaged in adaptation processes that are
      normative to youth with immigrant backgrounds, in terms of constructing
      supportive networks and developing culture competence. In accordance with the
      main effect hypothesis, social support had direct effects on depression and
      indirect effects by increasing culture competence that may aid the young refugees
      in dealing with discrimination. However, there were no effects of social support
      on symptoms of PTSD. The findings give direction to areas of interventions,
      beyond dealing with the sequel of the traumas the unaccompanied minors have been
      exposed to, not only for clinicians, but also social workers and school
      personnel.

PMID- 25614277
TI  - Streptococcus pneumoniae and Staphylococcus aureus carriage in healthy school-age
      children and adolescents.
AB  - Streptococcus pneumoniae and Staphylococcus aureus are common commensals of the
      upper respiratory tract in children and adolescents. Understanding the
      relationship between these two pathogens, including their potential for mutual
      interference, is needed to evaluate the epidemiology of the diseases they cause,
      the factors that condition acquisition and carriage, and the impact of related
      preventative measures. We obtained oropharyngeal and nasal swabs from 497 healthy
      subjects aged 6-17 years. S. pneumoniae detection and serotyping were performed
      using a real-time PCR and S. aureus detection was performed using the RIDAGENE
      MRSA system. We found that 136 (27.3%) of the children were carriers of both
      species, 121 (24.3%) of the children carried S. pneumoniae alone and 128 (25.7%)
      of the children carried S. aureus alone. S. aureus carriage was similar between
      children who carried S. pneumoniae (136/257, 52.9 %, 95% confidence interval
      [CI]: 46.8-58.9%) vs those who did not (128/240, 53.3%, 95% CI: 47.0 -59.5%) and
      was independent of age and vaccination with 7-valent pneumococcal conjugate
      vaccine (PCV7). Vaccination with PCV7 did not affect S. aureus carriage [S.
      pneumoniae: 84/143 (58.7%, 95% CI: 50.5 -66.5%) vaccinated children vs 171/351
      (48.7%, 95% CI: 43.5 -53.9%) unvaccinated children; S. aureus: 67/143 (46.9%, 95%
      CI: 38.9-55.0 %) vaccinated children vs 195/351 (55.6%, 95% CI: 50.3 -60.7%)
      unvaccinated children]. Pneumococcal serotype also did not appear to affect S.
      aureus carriage. These findings suggested that the carriage of S. pneumoniae did
      not affect that of S. aureus in older children and adolescents, regardless of
      age, PCV7 vaccination and pneumococcal serotype.

PMID- 25614278
TI  - Myocardin regulates vascular smooth muscle cell inflammatory activation and
      disease.
AB  - OBJECTIVE: Atherosclerosis, the cause of 50% of deaths in westernized societies,
      is widely regarded as a chronic vascular inflammatory disease. Vascular smooth
      muscle cell (VSMC) inflammatory activation in response to local proinflammatory
      stimuli contributes to disease progression and is a pervasive feature in
      developing atherosclerotic plaques. Therefore, it is of considerable therapeutic
      importance to identify mechanisms that regulate the VSMC inflammatory response.
      APPROACH AND RESULTS: We report that myocardin, a powerful myogenic
      transcriptional coactivator, negatively regulates VSMC inflammatory activation
      and vascular disease. Myocardin levels are reduced during atherosclerosis, in
      association with phenotypic switching of smooth muscle cells. Myocardin
      deficiency accelerates atherogenesis in hypercholesterolemic apolipoprotein E(-/
      ) mice. Conversely, increased myocardin expression potently abrogates the
      induction of an array of inflammatory cytokines, chemokines, and adhesion
      molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake,
      macrophage interaction, chemotaxis, and macrophage-endothelial tethering in
      vitro, and attenuates monocyte accumulation within developing lesions in vivo.
      These results demonstrate that endogenous levels of myocardin are a critical
      regulator of vessel inflammation. CONCLUSIONS: We propose myocardin as a guardian
      of the contractile, noninflammatory VSMC phenotype, with loss of myocardin
      representing a critical permissive step in the process of phenotypic transition
      and inflammatory activation, at the onset of vascular disease.

PMID- 25614279
TI  - Pivotal role of serum- and glucocorticoid-inducible kinase 1 in vascular
      inflammation and atherogenesis.
AB  - OBJECTIVE: Atherosclerosis, an inflammatory disease of arterial vessel walls,
      requires migration and matrix metalloproteinase (MMP)-9-dependent invasion of
      monocytes/macrophages into the vascular wall. MMP-9 expression is stimulated by
      transcription factor nuclear factor-kappaB, which is regulated by inhibitor
      kappaB (IkappaB) and thus IkappaB kinase. Regulators of nuclear factor-kappaB
      include serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study
      explored involvement of SGK1 in vascular inflammation and atherogenesis. APPROACH
      AND RESULTS: Gene-targeted apolipoprotein E (ApoE)-deficient mice without (apoe(
      /-)sgk1(+/+)) or with (apoe(-/-)sgk1(-/-)) additional SGK1 knockout received 16
      week cholesterol-rich diet. According to immunohistochemistry atherosclerotic
      lesions in aorta and carotid artery, vascular CD45(+) leukocyte infiltration, Mac
      3(+) macrophage infiltration, vascular smooth muscle cell content, MMP-2, and MMP
      9 positive areas in atherosclerotic tissue were significantly less in apoe(-/
      )sgk1(-/-)mice than in apoe(-/-)sgk1(+/+)mice. As determined by Boyden chamber,
      thioglycollate-induced peritonitis and air pouch model, migration of SGK1
      deficient CD11b(+)F4/80(+) macrophages was significantly diminished in vitro and
      in vivo. Zymographic MMP-2 and MMP-9 production, MMP-9 activity and invasion
      through matrigel in vitro were significantly less in sgk1(-/-) than in
      sgk1(+/+)macrophages and in control plasmid-transfected or inactive (K127N)SGK1
      transfected than in constitutively active (S422D)SGK1-transfected THP-1 cells.
      Confocal microscopy revealed reduced macrophage number and macrophage MMP-9
      content in plaques of apoe(-/-)sgk1(-/-) mice. In THP-1 cells, MMP-inhibitor
      GM6001 (25 MUmol/L) abrogated (S422D)SGK1-induced MMP-9 production and invasion.
      According to reverse transcription polymerase chain reaction, MMP-9 transcript
      levels were significantly reduced in sgk1(-/-)macrophages and strongly
      upregulated in (S422D)SGK1-transfected THP-1 cells compared with control plasmid
      transfected or (K127N)SGK1-transfected THP-1 cells. According to immunoblotting
      and confocal microscopy, phosphorylation of IkappaB kinase and inhibitor kappaB
      and nuclear translocation of p50 were significantly lower in sgk1(-/-)macrophages
      than in sgk1(+/+)macrophages and significantly higher in (S422D)SGK1-transfected
      THP-1 cells than in control plasmid-transfected or (K127N)SGK1-transfected THP-1
      cells. Treatment of (S422D)SGK1-transfected THP-1 cells with IkappaB kinase
      inhibitor BMS-345541 (10 MUmol/L) abolished (S422D)SGK1-induced increase of MMP-9
      transcription and gelatinase activity. CONCLUSIONS: SGK1 plays a pivotal role in
      vascular inflammation during atherogenesis. SGK1 participates in the regulation
      of monocyte/macrophage migration and MMP-9 transcription via regulation of
      nuclear factor-kappaB.

PMID- 25614280
TI  - Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces
      lipoprotein(a) in various populations with hypercholesterolemia: results of 4
      phase III trials.
AB  - OBJECTIVE: Lp(a) is an independent, causal, genetic risk factor for
      cardiovascular disease and aortic stenosis. Current pharmacological lipid
      lowering therapies do not optimally lower Lp(a), particularly in patients with
      familial hypercholesterolemia (FH). APPROACH AND RESULTS: In 4 phase III trials,
      382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to
      weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks.
      Populations included homozygous FH, heterozygous FH with concomitant coronary
      artery disease (CAD), severe hypercholesterolemia, and hypercholesterolemia at
      high risk for CAD. Lp(a) was measured 8* between baseline and week 28 inclusive.
      Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 and >50 mg/dL,
      respectively. In the pooled analysis, the mean percent decrease (median,
      interquartile range in Lp(a) at 28 weeks was significantly greater in the
      mipomersen group compared with placebo (-26.4 [-42.8, -5.4] versus -0.0 [-10.7,
      15.3]; P<0.001). In the mipomersen group in patients with Lp(a) levels >30 or >50
      mg/dL, attainment of Lp(a) values <=30 or <=50 mg/dL was most frequent in
      homozygous FH and severe hypercholesterolemia patients. In the combined groups,
      modest correlations were present between percent change in apolipoprotein B-100
      and Lp(a) (r=0.43; P<0.001) and low-density lipoprotein cholesterol and Lp(a)
      (r=0.36; P<0.001) plasma levels. CONCLUSIONS: Mipomersen consistently and
      effectively reduced Lp(a) levels in patients with a variety of lipid
      abnormalities and cardiovascular risk. Modest correlations were present between
      apolipoprotein B-100 and Lp(a) lowering but the mechanistic relevance mediating
      Lp(a) reduction is currently unknown.

PMID- 25614281
TI  - Gestational diabetes mellitus impairs fetal endothelial cell functions through a
      mechanism involving microRNA-101 and histone methyltransferase enhancer of zester
      homolog-2.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) produces fetal hyperglycemia with
      increased lifelong risks for the exposed offspring of cardiovascular and other
      diseases. Epigenetic mechanisms induce long-term gene expression changes in
      response to in utero environmental perturbations. Moreover, microRNAs (miRs)
      control the function of endothelial cells (ECs) under physiological and
      pathological conditions and can target the epigenetic machinery. We investigated
      the functional and expressional effect of GDM on human fetal ECs of the umbilical
      cord vein (HUVECs). We focused on miR-101 and 1 of its targets, enhancer of
      zester homolog-2 (EZH2), which trimethylates the lysine 27 of histone 3, thus
      repressing gene transcription. EZH2 exists as isoforms alpha and beta. APPROACH
      AND RESULTS: HUVECs were prepared from GDM or healthy pregnancies and tested in
      apoptosis, migration, and Matrigel assays. GDM-HUVECs demonstrated decreased
      functional capacities, increased miR-101 expression, and reduced EZH2- beta and
      trimethylation of histone H3 on lysine 27 levels. MiR-101 inhibition increased
      EZH2 expression and improved GDM-HUVEC function. Healthy HUVECs were exposed to
      high or normal d-glucose concentration for 48 hours and then tested for miR-101
      and EZH2 expression. Similar to GDM, high glucose increased miR-101 expression.
      Chromatin immunoprecipitation using an antibody for EZH2 followed by polymerase
      chain reaction analyses for miR-101 gene promoter regions showed that both GDM
      and high glucose concentration reduced EZH2 binding to the miR-101 locus in
      HUVECs. Moreover, EZH2-beta overexpression inhibited miR-101 promoter activity in
      HUVECs. CONCLUSIONS: GDM impairs HUVEC function via miR-101 upregulation. EZH2 is
      both a transcriptional inhibitor and a target gene of miR-101 in HUVECs, and it
      contributes to some of the miR-101-induced defects of GDM-HUVECs.

PMID- 25614282
TI  - Role of oral anticoagulants in patients after an acute coronary syndrome.
AB  - After an acute coronary syndrome, patients continue to be at risk of adverse
      cardiovascular events despite treatment with the current standard of
      antithrombotic therapy. The risk may be in part secondary to thrombin, which
      remains elevated after an acute coronary syndrome event. Several studies have
      investigated the utility of adding oral anticoagulation to post-acute coronary
      syndrome medical regimens, with the most promising results coming from the
      addition of low-dose oral direct anticoagulants. Focusing on optimal dosing
      strategies and applying therapies to the appropriate populations provide the
      ability to maximize benefit and minimize risk. 

PMID- 25614283
TI  - Galectin-3 predicts long-term cardiovascular death in high-risk patients with
      coronary artery disease.
AB  - OBJECTIVE: Galectin-3 (Gal-3) can affect atherogenesis by multiple mechanisms,
      but it remains scarcely known whether plasma Gal-3 levels predict cardiovascular
      events in patients with coronary artery disease. Therefore, we investigated if
      Gal-3 predicts cardiovascular death in patients with coronary artery disease of
      the Genetic and ENvironmental factors In Coronary Artery disease study. APPROACH
      AND RESULTS: In a prospective cohort study, we measured the plasma levels of Gal
      3 in 1013 randomly selected patients who underwent coronary angiography and long
      term follow-up to assess incident cardiovascular events. The primary end points
      were (1) cardiovascular death and (2) a composite of cardiovascular death, acute
      coronary syndrome, and stroke. Secondary end points entailed (1) acute myocardial
      infarction, (2) stroke, and (3) a composite fatal ischemic event including fatal
      myocardial infarction and stroke. The effect of Gal-3 on prognosis was assessed
      using Kaplan-Meier analysis and multivariate Cox's regression. During long-term
      follow-up (median, 7.2 years), 115 cardiovascular deaths occurred (15.2%), more
      commonly in the high Gal-3 tertile (25.2%) than in the intermediate and the low
      tertiles (13.6% versus 7.5%, respectively; P<0.001). The adverse prognostic
      effect of high Gal-3 was confirmed in subgroup analysis of the patients with
      angiographically documented coronary artery disease and also of those with a
      normal left ventricular ejection fraction. At multivariate analysis, Gal-3 was a
      predictor of cardiovascular mortality (hazard ratio, 1.79; 95% confidence
      interval, 1.10-2.93; P=0.020) along with age, left ventricular ejection fraction,
      and coronary atherosclerotic burden. CONCLUSIONS: In high cardiovascular risk
      patients referred for coronary angiography Gal-3 is a strong independent
      predictor of cardiovascular death.

PMID- 25614284
TI  - Fibrin, gamma'-fibrinogen, and transclot pressure gradient control hemostatic
      clot growth during human blood flow over a collagen/tissue factor wound.
AB  - OBJECTIVE: Biological and physical factors interact to modulate blood response in
      a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow
      and pressure differential (DeltaP) across the wound from the lumen to the
      extravascular compartment may impact hemostasis and the observed core/shell
      architecture. We examined physical and biological factors responsible for
      regulating thrombin-mediated clot growth. APPROACH AND RESULTS: Using factor XIIa
      inhibited human whole blood perfused in a microfluidic device over
      collagen/tissue factor at controlled wall shear rate and DeltaP, we found
      thrombin to be highly localized in the P-selectin(+) core of hemostatic clots.
      Increasing DeltaP from 9 to 29 mm Hg (wall shear rate=400 s(-1)) reduced P
      selectin(+) core size and total clot size because of enhanced extravasation of
      thrombin. Blockade of fibrin polymerization with 5 mmol/L Gly-Pro-Arg-Pro
      dysregulated hemostasis by enhancing both P-selectin(+) core size and clot size
      at 400 s(-1) (20 mm Hg). For whole-blood flow (no Gly-Pro-Arg-Pro), the thickness
      of the P-selectin-negative shell was reduced under arterial conditions (2000 s(
      1), 20 mm Hg). Consistent with the antithrombin-1 activity of fibrin implicated
      with Gly-Pro-Arg-Pro, anti-gamma'-fibrinogen antibody enhanced core-localized
      thrombin, core size, and overall clot size, especially at venous (100 s(-1)) but
      not arterial wall shear rates (2000 s(-1)). Pathological shear (15 000 s(-1)) and
      Gly-Pro-Arg-Pro synergized to exacerbate clot growth. CONCLUSIONS: Hemostatic
      clotting was dependent on core-localized thrombin that (1) triggered platelet P
      selectin display and (2) was highly regulated by fibrin and the transclot DeltaP.
      Also, gamma'-fibrinogen had a role in venous but not arterial conditions.

PMID- 25614285
TI  - Wnt16 attenuates TGFbeta-induced chondrogenic transformation in vascular smooth
      muscle.
AB  - OBJECTIVE: Phenotypic plasticity of vascular smooth muscle cells (VSMCs)
      contributes to cardiovascular disease. Chondrocyte-like transformation of VSMCs
      associates with vascular calcification and underlies the formation of aortic
      cartilaginous metaplasia induced in mice by genetic loss of matrix Gla protein
      (MGP). Previous microarray analysis identified a dramatic downregulation of Wnt16
      in calcified MGP-null aortae, suggesting an antagonistic role for Wnt16 in the
      chondrogenic transformation of VSMCs. APPROACH AND RESULTS: Wnt16 is
      significantly downregulated in MGP-null aortae, before the histological
      appearance of cartilaginous metaplasia, and in primary MGP-null VSMCs. In
      contrast, intrinsic TGFbeta is activated in MGP-null VSMCs and is necessary for
      spontaneous chondrogenesis of these cells in high-density micromass cultures.
      TGFbeta3-induced chondrogenic transformation in wild-type VSMCs associates with
      Smad2/3-dependent Wnt16 downregulation, but Wnt16 does not suppress TGFbeta3
      induced Smad activation. In addition, TGFbeta3 inhibits Notch signaling in wild
      type VSMCs, and this pathway is downregulated in MGP-null aortae. Exogenous Wnt16
      stimulates Notch activity and attenuates TGFbeta3-induced downregulation of Notch
      in wild-type VSMCs, prevents chondrogenesis in MGP-null and TGFbeta3-treated wild
      type VSMCs, and stabilizes expression of contractile markers of differentiated
      VSMCs. CONCLUSIONS: We describe a novel TGFbeta-Wnt16-Notch signaling conduit in
      the chondrocyte-like transformation of VSMCs and identify endogenous TGFbeta
      activity in MGP-null VSMCs as a critical mediator of chondrogenesis. Our proposed
      model suggests that the activated TGFbeta pathway inhibits expression of Wnt16,
      which is a positive regulator of Notch signaling and a stabilizer of VSMC
      phenotype. These data advance the comprehensive mechanistic understanding of VSMC
      transformation and may identify a novel potential therapeutic target in vascular
      calcification.

PMID- 25614286
TI  - Dimorphic effects of transforming growth factor-beta signaling during aortic
      aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome.
AB  - OBJECTIVE: Studies of mice with mild Marfan syndrome (MFS) have correlated the
      development of thoracic aortic aneurysm (TAA) with improper stimulation of
      noncanonical (Erk-mediated) TGFbeta signaling by the angiotensin type I receptor
      (AT1r). This correlation was largely based on comparable TAA modifications by
      either systemic TGFbeta neutralization or AT1r antagonism. However, subsequent
      investigations have called into question some key aspects of this mechanism of
      arterial disease in MFS. To resolve these controversial points, here we made a
      head-to-head comparison of the therapeutic benefits of TGFbeta neutralization and
      AT1r antagonism in mice with progressively severe MFS (Fbn1(mgR/mgR) mice).
      APPROACH AND RESULTS: Aneurysm growth, media degeneration, aortic levels of
      phosphorylated Erk and Smad proteins and the average survival of Fbn1(mgR/mgR)
      mice were compared after a ~3-month-long treatment with placebo and either the
      AT1r antagonist losartan or the TGFbeta-neutralizing antibody 1D11. In contrast
      to the beneficial effect of losartan, TGFbeta neutralization either exacerbated
      or mitigated TAA formation depending on whether treatment was initiated before
      (postnatal day 16; P16) or after (P45) aneurysm formation, respectively.
      Biochemical evidence-related aneurysm growth with Erk-mediated AT1r signaling,
      and medial degeneration with TGFbeta hyperactivity that was in part AT1r
      dependent. Importantly, P16-initiated treatment with losartan combined with P45
      initiated administration of 1D11 prevented death of Fbn1(mgR/mgR) mice from
      ruptured TAA. CONCLUSIONS: By demonstrating that promiscuous AT1r and TGFbeta
      drive partially overlapping processes of arterial disease in MFS mice, our study
      argues for a therapeutic strategy against TAA that targets both signaling
      pathways although sparing the early protective role of TGFbeta.

PMID- 25614288
TI  - Synthesis of directly fused porphyrin dimers through Fe(OTf)3-mediated oxidative
      coupling.
AB  - An efficient and general Fe(OTf)3-mediated oxidative coupling method was
      developed for the synthesis of doubly or triply linked porphyrin dimers. Besides
      the central metal and peripheral substituent, regioselectivity of the oxidative
      coupling was found to be closely relevant to the onset oxidation potential of the
      porphyrin substrate, and the reactant with higher E(onset(ox)) tends to generate
      meso-beta doubly fused porphyrin dimer.

PMID- 25614289
TI  - Attack of the cloned reports.

PMID- 25614287
TI  - Impaired integrin beta3 delays endothelial cell regeneration and contributes to
      arteriovenous graft failure in mice.
AB  - OBJECTIVE: Neointima formation is associated with stenosis and subsequent
      thrombosis in arteriovenous grafts (AVGs). A role of integrin beta3 in the
      neointima formation of AVGs remains poorly understood. APPROACH AND RESULTS: In
      integrin beta3(-/-) mice, we found significantly accelerated occlusion of AVGs
      compared with the wild-type mice. This is caused by the development of neointima
      and lack of endothelial regeneration. The latter is a direct consequence of
      impaired functions of circulating angiogenic cells (CACs) and platelets in
      integrin beta3(-/-) mice. Evidence suggests the involvement of platelet
      regulating CAC homing to and differentiation at graft sites via transforming
      growth factor-beta1 and Notch signaling pathway. First, CACs deficient of
      integrin beta3 impaired adhesion activity toward exposed subendothelium. Second,
      platelets from integrin beta3(-/-) mice failed to sufficiently stimulate CACs to
      differentiate into mature endothelial cells. Finally, we found that transforming
      growth factor-beta1 level was increased in platelets from integrin beta3(-/-)
      mice and resulted in enhanced Notch1 activation in CACs in AVGs. These results
      demonstrate that integrin beta3 is critical for endothelial cell homing and
      differentiation. The increased transforming growth factor-beta1 and Notch1
      signaling mediates integrin beta3(-/-)-induced AVG occlusion. This accelerated
      occlusion of AVGs was reversed in integrin beta3(-/-) mice transplanted with the
      bone marrow from wild-type mice. CONCLUSIONS: Our results suggest that boosting
      integrin beta3 function in the endothelial cells and platelets could prevent
      neointima and thrombosis in AVGs.

PMID- 25614290
TI  - Nanobiocomposite of poly(lactide-co-glycolide)/chitosan electrospun scaffold can
      promote proliferation and transdifferentiation of Schwann-like cells from human
      adipose-derived stem cells.
AB  - The transdifferentiation of human adipose-derived stem cells (ADSCs) into Schwann
      like cells on biocomposite scaffolds may be a critical issue in nerve
      regeneration medicine. In this study, tissue-engineered scaffold with chitosan
      (CS) nanopowders and poly(lactide-co-glycolide) (PLGA) was investigated for its
      potential Schwann cells (SCs) transdifferentiation. The differentiation of human
      ADSCs into S-like cells was induced with different CS content and direction of
      nanofibers on PLGA/CS scaffolds. Cell morphology and proliferation of
      differentiated cells were investigated by scanning electron microscopy and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay respectively. For
      assessment efficiency of transdifferentiation, the expression of SC markers
      (glial fibrillary acidic protein and S100), and myelinogenic marker (myelin basic
      protein) was investigated in different nanochitosan content and direction of
      nanofibers scaffolds, using immunocytochemistry technique. The nanochitosan can
      significantly promote cell proliferation of differentiated cells (p < 0.05). The
      mean percentage of S-like cells on greater CS content nanofibers scaffold was
      significantly higher than others (p < 0.05). In addition, the align orientation
      of nanofibers in scaffolds guided the differentiation of ADSCs toward myelinating
      S-like cells on the constructs. Overall, we found that high CS content and
      aligned-orientation of nanofibers in biocomposite scaffold (70/30A) can promote
      differentiation and myelinogenic capacity of S-like cells induced from human
      ADSCs.

PMID- 25614291
TI  - Towards co-evolution of membrane proteins and metabolism.
AB  - Primordial metabolism co-evolved with the earliest membrane peptides to produce
      more environmentally fit progeny. Here, we map a continuous, evolutionary path
      that connects nascent biochemistry with simple, membrane-bound oligopeptides, ion
      channels and, further, membrane proteins capable of energy transduction and
      utilization of energy for active transport. 

PMID- 25614292
TI  - Major adverse cardiac and bleeding events associated with non-cardiac surgery in
      coronary artery disease patients with or without prior percutaneous coronary
      intervention.
AB  - BACKGROUND: The optimal preoperative therapeutic strategy for patients with
      coronary artery disease (CAD) is an important concern in the era of drug-eluting
      stents and antiplatelet therapy. However, there are few studies about the impact
      of prior percutaneous coronary intervention (PCI) on perioperative major adverse
      cardiac events (MACEs) and bleeding events associated with oral antiplatelet
      therapy. The aim of this study was to examine the risks and benefits of
      performing PCI before non-cardiac surgery (NCS) in patients with CAD. METHODS: We
      investigated 130 patients who had angiographically significant and stable CAD and
      underwent NCS after index coronary angiography. We divided the patients into two
      groups: patients undergoing PCI with coronary stenting (PCI group), and those not
      undergoing PCI before NCS (no-PCI group), and compared the MACEs and bleeding
      events within 30 days from NCS between the groups. RESULTS: There were 53 and 77
      patients in the PCI and no-PCI groups, respectively. MACEs were observed in 2
      patients (3.8%) in the PCI group and 3 patients (3.9%) in the no-PCI group
      (p=0.97), whereas bleeding events were observed in 10 (18.9%) and 8 patients
      (10.4%) in the PCI and no-PCI groups, respectively (p=0.17). There were no
      significant differences between the two groups in terms of MACEs and bleeding
      events. CONCLUSIONS: The rate of MACEs following NCS was not significantly
      different between the PCI and no-PCI groups, while the rate of bleeding events
      was higher in the PCI group without reaching statistical significance. This study
      suggests that patients with stable CAD may be able to safely undergo NCS without
      revascularization even in the presence of significant coronary artery stenosis.

PMID- 25614293
TI  - Binary polyazides of cadmium and mercury.
AB  - Following our interest in binary element-nitrogen compounds we report here on the
      synthesis and comprehensive characterization (M.p., IR/Raman, elemental analysis,
      (14)N/(133)Cd/(199)Hg NMR) of tri- and tetraazido cadmate and mercurate anions
      [E(N3)(2+n)](n-) (E = Cd, Hg; n=1, 2) in a series of [Ph4P](+) and [PNP](+)
      ([PNP](+) = bis(triphenylphosphine)iminium) salts. The azide/chloride exchange in
      CH2Cl2 as well as the formation of tetrazolate salts in CH3CN solutions of the
      polyazido mercurates were investigated. Single crystal X-ray structures of all
      new compounds, and for comparison [Ph4P][Cd2(N3)5(H2O)], were determined.
      Moreover, the synthesis of anhydrous cadmium(II) azide and its DMSO adduct is
      presented for the first time. For a better understanding of structure and bonding
      in E(N3)2, [E(N3)3](-) and [E(N3)4](2-), theoretical calculations at the M06
      2X/aug-cc-pVDZ level were carried out.

PMID- 25614294
TI  - Case series of familial frontal fibrosing alopecia and a review of the
      literature.
AB  - Frontal fibrosing alopecia (FFA) is a distinctive form of scarring alopecia
      presenting with partial eyebrow loss and frontal temporal parietal recession of
      the hairline. Its etiology remains unknown, and there is no definitive treatment.
      Information in familial cases of FFA is scarce. We conducted a retrospective
      cohort study describing the mean clinical findings, treatment, and also the mean
      differences between premenopausal and postmenopausal cases of familiar FFA. Data
      analysis from case was performed on eight patients with a familiar history and
      diagnosis of FFA seen at the Alicante Aesthetic Dermatology Centre between
      January 2009 and June 2014. All patients in this cohort were females. Mean age at
      onset was 65 year (range 60-75) in the postmenopausal patients and 39 year (range
      33-47) in the premenopausal women. All menopausal patients were in an advanced
      stage when the disease had already developed in the frontal and/or temporal
      parietal hairline region. However, the daughters, all of them premenopausal age,
      attended the consultation with mild involvement of the eyebrows in all four cases
      and mild impairment of the frontal hairline in three of them. Specific clinical
      findings in familial FFA are poorly communicated until nowadays although the
      number of familial cases arises until 8% in the main case series published in
      recent years. Early diagnosis in premenopausal stage is frequent in our case
      series and allows us to begin the protocol treatment in the first stage of the
      disease, but long-term progression will remain uncertain until a definitive
      treatment could be established by multicenter randomized controlled trials. 

PMID- 25614295
TI  - Dinuclear copper intermediates in copper(I)-catalyzed azide-alkyne cycloaddition
      directly observed by electrospray ionization mass spectrometry.
AB  - The mechanism of the CuAAC reaction has been investigated by electrospray
      ionization mass spectrometry (ESI-MS) using a combination of the neutral reactant
      approach and the ion-tagging strategy. Under these conditions, for the first
      time, putative dinuclear copper intermediates were fished out and characterized
      by ESI(+)-MS/MS. New insight into the CuAAC reaction mechanisms is provided and a
      catalytic cycle is proposed. 

PMID- 25614296
TI  - The prevalence of potentially modifiable functional deficits and the subsequent
      use of occupational and physical therapy by older adults with cancer.
AB  - BACKGROUND: Occupational and physical therapy (OT/PT) services seek to reduce
      morbidity, mortality, and improve the quality of life of individuals; however,
      little is known about the needs and use of OT/PT for older adults with cancer.
      The goal of this study was to describe the functional deficits and their
      associations with other factors, and to examine the use of OT/PT after a noted
      functional deficit. MATERIALS AND METHODS: This study analyzed data from an
      institution-based registry that included geriatric assessments of older adults
      with cancer linked to billing claims data. Logistic regression was used to model
      predictors of functional deficits. Use of OT/PT was determined and validated with
      medical chart review. RESULTS: 529 patients with cancer, a median age of 71, 78%
      were female, 87% Caucasian, 57% married, 53% post-secondary education, and 63%
      with breast cancer were included. In a multivariable model, the odds of having
      any functional deficits increased with age [5 year OR: 1.31, 95% CI: (1.10,
      1.57)] were higher for those with a high school diploma versus those with
      advanced degrees [OR: 1.66, 95% CI: (1.00, 2.77)] and were higher for patients
      with comorbidities [OR: 1.15, 95% CI: (1.10, 1.21)]. Of patients with functional
      deficits only 9% (10/111) received OT/PT within 12 months of a noted deficit.
      DISCUSSION: The odds of having any potentially modifiable functional deficit were
      higher in patients with increasing age, comorbid conditions, and with less than a
      college degree. Few were referred for OT/PT services suggesting major
      underutilization of these potentially beneficial services.

PMID- 25614298
TI  - Modified fields' stain: ideal to differentiate Dientamoeba fragilis and
      Blastocystis sp.
AB  - Dientamoeba fragilis, a trichomonad parasite is usually found in the
      gastrointestinal tract of human, and it is known to be the cause for
      gastrointestinal disease. The parasite is globally distributed and mostly found
      in rural and urban areas. The parasite is found in humans and nonhuman primates
      such as the macaques, baboons, and gorillas. Often, the parasite is confused with
      another largely found organism in stools called Blastocystis sp. especially when
      seen directly under light microscopy on culture samples containing both
      parasites. Both sometimes are seen with two nuclei with sizes tending to be
      similar which complicates identification. Stools were collected fresh from nine
      previously diagnosed persons infected with D. fragilis who also were found to be
      positive for Blastocystis sp. Samples were then cultured in Loeffler's medium and
      were stained with Giemsa, iron hematoxylin, and modified Fields' (MF) stain,
      respectively. D. fragilis was differentiated from Blastocystis sp. when stained
      with MF stain by the presence of a thinner outer membrane with clearly demarcated
      nuclei in the center of the cell whilst Blastocystis sp. had a darker and thicker
      stained outer membrane with the presence of two nuclei. The staining contrast was
      more evident with modified Fields' stain when compared with the other two. The
      simplicity in preparing the stain as well as the speed of the staining procedure
      make MF stain an ideal alternate. The modified Fields' stain is faster and easier
      to prepare when compared to the other two stains. MF stain provides a better
      contrast differentiating the two organisms and therefore provides a more reliable
      diagnostic method to precisely identify one from the other especially when
      cultures show mixed infections.

PMID- 25614297
TI  - Comparative effectiveness of anthracycline-containing chemotherapy in United
      States veterans age 80 and older with diffuse large B-cell lymphoma.
AB  - OBJECTIVES: While anthracycline-based treatment can cure diffuse large B-cell
      lymphoma, most patients over age 80 do not receive doxorubicin due to toxicity
      concerns. This study evaluated this practice, as patients age 80 and older are
      largely excluded from clinical trials. The primary outcome of interest was
      overall survival. Secondary outcomes included treatment-related mortality and
      anthracycline dose intensity. MATERIALS AND METHODS: We assembled a cohort of 530
      newly diagnosed diffuse large B-cell lymphoma patients age 80 or older diagnosed
      within United States Veterans Health Administration. Treatment and survival
      information were obtained to determine associations between anthracycline use,
      dose intensity, treatment-related mortality and overall survival. RESULTS: Of the
      530 patients, 285 received systemic treatment and 193 received an anthracycline.
      After controlling for potential confounders, rituximab decreased mortality
      (hazard ratio, 0.62; 95% confidence interval [CI]: 0.44-0.88), while doxorubicin
      was not significantly associated with mortality (hazard ratio, 0.87; 95% CI: 0.64
      1.17). Completion of treatment with anthracycline dose intensity >=85% of
      expected was only 14%. Patients treated with anthracycline dose intensity <85%
      had better one year survival compared to those treated at >=85% (70% vs. 59%,
      p=0.029). CONCLUSION: These results suggest that full dose anthracycline therapy
      may be less important in the treatment of diffuse large B-cell lymphoma patients
      over age 80. The low frequency of completion of full dose intensity treatment
      suggests that standard doses are an unrealistic standard of care for patients
      this age. Alternate treatment strategies and risk stratification should be
      considered for these patients.

PMID- 25614299
TI  - A heteroscedastic measurement error model for method comparison data with
      replicate measurements.
AB  - Measurement error models offer a flexible framework for modeling data collected
      in studies comparing methods of quantitative measurement. These models generally
      make two simplifying assumptions: (i) the measurements are homoscedastic, and
      (ii) the unobservable true values of the methods are linearly related. One or
      both of these assumptions may be violated in practice. In particular, error
      variabilities of the methods may depend on the magnitude of measurement, or the
      true values may be nonlinearly related. Data with these features call for a
      heteroscedastic measurement error model that allows nonlinear relationships in
      the true values. We present such a model for the case when the measurements are
      replicated, discuss its fitting, and explain how to evaluate similarity of
      measurement methods and agreement between them, which are two common goals of
      data analysis, under this model. Model fitting involves dealing with lack of a
      closed form for the likelihood function. We consider estimation methods that
      approximate either the likelihood or the model to yield approximate maximum
      likelihood estimates. The fitting methods are evaluated in a simulation study.
      The proposed methodology is used to analyze a cholesterol dataset.

PMID- 25614300
TI  - MBSTAR: multiple instance learning for predicting specific functional binding
      sites in microRNA targets.
AB  - MicroRNA (miRNA) regulates gene expression by binding to specific sites in the
      3'untranslated regions of its target genes. Machine learning based miRNA target
      prediction algorithms first extract a set of features from potential binding
      sites (PBSs) in the mRNA and then train a classifier to distinguish targets from
      non-targets. However, they do not consider whether the PBSs are functional or
      not, and consequently result in high false positive rates. This substantially
      affects the follow up functional validation by experiments. We present a novel
      machine learning based approach, MBSTAR (Multiple instance learning of Binding
      Sites of miRNA TARgets), for accurate prediction of true or functional miRNA
      binding sites. Multiple instance learning framework is adopted to handle the lack
      of information about the actual binding sites in the target mRNAs. Biologically
      validated 9531 interacting and 973 non-interacting miRNA-mRNA pairs are
      identified from Tarbase 6.0 and confirmed with PAR-CLIP dataset. It is found that
      MBSTAR achieves the highest number of binding sites overlapping with PAR-CLIP
      with maximum F-Score of 0.337. Compared to the other methods, MBSTAR also
      predicts target mRNAs with highest accuracy. The tool and genome wide predictions
      are available at http://www.isical.ac.in/~bioinfo_miu/MBStar30.htm. 

PMID- 25614301
TI  - Fatal superior sagittal sinus hemorrhage as a complication of aplasia cutis
      congenita: a case report and literature review.
AB  - Aplasia cutis congenita (ACC) is a rare condition that occurs in around 0.01% of
      births. Characterized by a localized absence of skin, it affects the midline of
      the scalp in over 80% of cases. We describe the case of an infant born via
      vaginal spontaneous delivery with ACC affecting the scalp. This extended to the
      subcutaneous tissue and bone leaving the dura mater exposed. The patient was
      managed conservatively. At 4 weeks of age, she had a fatal superior sagittal
      sinus hemorrhage. In a review of the literature, we found ten previous cases of
      hemorrhage of the superior sagittal sinus complicating an ACC. Including our
      case, ACC complicated by hemorrhage of the superior sagittal sinus shows a 36%
      mortality (4/11). An analysis of these cases suggests that this tends to occur
      between 1 and 3 months of age, though it may occur in younger neonates.

PMID- 25614302
TI  - Osteological evidence of remote penetrating soft tissue trauma in skeletal
      remains.

PMID- 25614303
TI  - A Santeria/Palo Mayombe ritual cauldron containing a human skull and multiple
      artifacts recovered in western Massachusetts, U.S.A.
AB  - Santeria and Palo Mayombe are West African-derived religions/sects with
      components of Catholicism, and both involve the ritual use of nonhuman skeletal
      remains which make them an increasing object of forensic interest. Palo Mayombe
      specifically involves also the use of human skeletal remains placed within ritual
      cauldrons or ngangas along with multiple ritual artifacts. A case of a nganga
      recovered from a periodically drained canal in Western Massachusetts, U.S.A. is
      presented. This nganga contained multiple items indicating its origin, including
      railroad spikes, coins, other metal objects, a stone, a glass bead, and multiple
      labeled and unlabeled sticks and was associated with a knife. It also contained
      skeletal remains of a bird and a snake as well as a nearly intact human skull of
      an adult male. The origin of the human remains is likely from a cemetery or as a
      former anatomical specimen. The find of this nganga is atypical in that it is
      away from the usual urban centers of Palo Mayombe in the U.S.A., and forensic
      practitioners should be aware that such sources of human remains may occur in
      their jurisdictions. 

PMID- 25614304
TI  - Discovery of Liopiophila varipes and Protopiophila contecta (Diptera:
      Piophilidae) from human cadavers.
AB  - Here, we present two cases in which larvae of the family Piophilidae were
      detected in human cadavers. Both cases were found in Tochigi Prefecture, which is
      located in the middle of Honshu Island, Japan. Case 1: A corpse was found hanging
      in the sun lounge of a house. Dipteran larvae were collected from inside the
      spinal canal, despite no visible breach on the skin. The adults derived from
      these larvae were identified as Piophila casei (Linnaeus, 1758) and Liopiophila
      varipes (Meigen, 1830). Case 2: Skeletal human remains were found in a
      mountainous forest. Dipteran larvae were detected in the bone marrow cavity of a
      tibial section during autopsy. One adult fly derived from the larvae was
      identified as Protopiophila contecta (Walker, 1860). This is the first report of
      the identification of L. varipes and P. contecta in human cadavers. 

PMID- 25614305
TI  - Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and
      Review of the Literature.
AB  - BACKGROUND: Lysinuric protein intolerance (LPI; MIM# 222700) is a rare metabolic
      disorder caused by a defective cationic amino acids (CAA) membrane transport
      leading to decreased circulating plasma CAA levels and resulting in dysfunction
      of the urea cycle. Short stature is commonly observed in children with LPI and
      has been associated with protein malnutrition. A correlation between LPI and
      growth hormone deficiency (GHD) has also been postulated because of the known
      interaction between the AA arginine, ornithine, and lysine and growth hormone
      (GH) secretion. Our report describes a case of GHD in an LPI patient, who has not
      presented a significant increase in growth velocity with recombinant-human GH
      (rhGH) therapy, suggesting some possible pathogenic mechanisms of growth failure.
      CASE PRESENTATION: The proband was a 6-year-old boy, diagnosed as suffering from
      LPI, erythrophagocytosis (HP) in bone marrow, and short stature. Two GH
      provocative tests revealed GHD. The patient started rhGH therapy and a controlled
      protein diet initially with supplementation of oral arginine and then of
      citrulline. At 3-year follow-up, no significant increase in growth velocity and
      in insulin-like growth factor-1 (IGF-1) levels was observed. Inadequate nutrition
      and low plasmatic levels of arginine, ornithine, lysine, and HP may have
      contributed to his poor growth. CONCLUSION: Our case suggests that growth failure
      in patients with GHD and LPI treated with rhGH could have a complex and
      multifactorial pathogenesis. Persistently low plasmatic levels of lysine,
      arginine, and ornithine, associated with dietary protein and caloric restriction
      and systemic inflammation, could determine a defect in coupling GH to IGF-1
      production explaining why GH replacement therapy is not able to significantly
      improve growth impairment. We hypothesize that a better understanding of growth
      failure pathophysiology in these patients could lead to the development of more
      rational strategies to treat short stature in patients with LPI.

PMID- 25614306
TI  - Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1)
      Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and
      Combined D,L-2-Hydroxyglutaric Aciduria.
AB  - Recessive mutations in SLC25A1 encoding mitochondrial citrate carrier cause a
      rare inherited metabolic disorder, combined D,L-2-hydroxyglutaric aciduria (D,L-2
      HGA), characterized by epileptic encephalopathy, respiratory insufficiency,
      developmental arrest and early death. Here, we describe two siblings compound
      heterozygotes for null/missense SLC25A1 mutations, c.18_24dup (p.Ala9Profs*82),
      and c.134C>T (p.Pro45Leu). These children presented with classic clinical
      features of D,L-2-HGA, but also showed marked facial dysmorphism. Additionally,
      there was prominent lactic acidosis in one of the siblings. Our observations
      suggest that facial dysmorphism is a previously unrecognized but an important
      diagnostic feature of SLC25A1 deficiency and expand the clinical phenotype linked
      to SLC25A1 mutations. 

PMID- 25614307
TI  - Expanding our understanding of lower urinary tract symptoms and incontinence in
      adults with pompe disease.
AB  - OBJECTIVE: To study the prevalence of lower urinary tract symptoms (LUTS) and
      incontinence in late-onset Pompe disease (LOPD) Methods: Adult LOPD patients seen
      at the Duke Pompe Clinic were prospectively recruited and asked to complete
      validated questionnaires on LUTS and incontinence as part of an IRB-approved
      study. Patient demographics as well as previous urologic history were reviewed.
      RESULTS: 35 patients with LOPD were included in the study (17 males and 18
      females). The median age was 51.8 (range 18-72 years of age). Of these patients,
      27/35 were receiving enzyme replacement therapy (ERT) with median duration of 54
      months (range 5-88 months). In the male patients, 9/17 (53%) described their
      stream as dribbling, weak, or intermittent, and 9/17 (53%) complained of post
      void dribbling. In addition 38% of the men were unable to stop their urination
      midstream. In the female patients, the most common complaint was urinary
      incontinence, reported in 14/18 (78%). In addition, 7/18 (39%) complained of post
      void dribbling, and 47% were unable to stop their urination midstream. Bowel
      incontinence was reported in 45% of patients. There was a significant association
      between urinary symptoms and lower extremity function scores and duration of ERT
      (p = 0.005 and p = 0.04, respectively) CONCLUSIONS: This is the first study in a
      large cohort of LOPD patients that demonstrates LUTS and incontinence occur at a
      high rate. This study emphasizes the spectrum of LOPD is beyond isolated gross
      motor and pulmonary involvement and has a significant effect on the lower urinary
      tract.

PMID- 25614308
TI  - Carnitine-acylcarnitine translocase deficiency: experience with four cases in
      Spain and review of the literature.
AB  - BACKGROUND: Carnitine-acylcarnitine translocase (CACT) deficiency is a rare
      autosomal recessive disease in the mitochondrial transport of long-chain fatty
      acids. Despite early diagnosis and treatment, the disease still has a high
      mortality rate. METHODS: Clinical symptoms, long-term follow-up, and biochemical
      and molecular results of four cases are described and compared with the reviewed
      literature data of 55 cases. RESULTS: Two cases with neonatal onset, carrying in
      homozygosity the novel variant sequences p.Gly20Asp (c.59G>A) and p.Arg179Gly
      (c.536A>G), died during an intercurrent infectious process in the first year of
      life despite adequate dietetic treatment (frequent feeding, high-carbohydrate/low
      fat diet, MCT, carnitine). The other two cases, one with infantile onset and the
      other diagnosed in the newborn period after a previous affected sibling, show
      excellent development at 4 and 16 years of age under treatment. The review shows
      that the most frequent presenting symptoms of CACT deficiency are hypoketotic
      hypoglycemia, hyperammonemia, hepatomegaly, cardiomyopathy and/or arrhythmia, and
      respiratory distress. The onset of symptoms is predominantly neonatal in 82% and
      infantile in 18%. The mortality rate is high (65%), most in the first year of
      life due to myocardiopathy or sudden death. Outcomes seem to correlate better
      with the absence of cardiac disease and with a higher long-chain fatty acid
      oxidation rate in cultured fibroblasts than with residual enzyme activity.
      CONCLUSION: Diagnosis before the occurrence of clinical symptoms by tandem MS-MS
      and very early therapeutic intervention together with good dietary compliance
      could lead to a better prognosis, especially in milder clinical cases.

PMID- 25614309
TI  - Morphology and function of cerebral arteries in adults with pompe disease.
AB  - OBJECTIVE: Cerebrovascular abnormalities have been reported in adult patients
      with Pompe disease. The objective was to study these abnormalities by (1)
      determining the diameter and mean flow velocity (MFV) of large cerebral arteries
      and (2) estimating cerebral blood flow (CBF), resistance index (RI) and
      cerebrovascular reactivity (CVR) as functions of resistance vessels. METHODS: In
      ten adults with Pompe disease and twenty controls, the diameter, peak systolic
      (PSV) and end-diastolic velocities (EDV) of arteries supplying the brain were
      quantified by MR angiography and sonography. MFV, RI and CBF were calculated. CVR
      in the middle cerebral artery (MCA) was determined by hyperventilation and
      acetazolamide injection. RESULTS: MR angiography revealed dilation of cerebral
      arteries predominantly in the posterior circulation. Dilative arteriopathy was
      found in three patients; two of them showed vertebrobasilar dolichoectasia.
      Despite of the dilative arteriopathy, the MFV was normal, indicating increased
      CBF and dilated resistance vessels. RI of all examined arteries and CVR of MCA
      were normal. CONCLUSION: The data suggest that dilation of small and large
      cerebral arteries is a common feature in adults with Pompe disease. Increased CBF
      might be the consequence of dilated resistance vessels. However, dysfunction of
      resistance vessels was rarely found. SYNOPSIS: In adults with Pompe disease,
      dilation of small and large cerebral arteries is a common feature and might be
      associated with increased cerebral blood flow.

PMID- 25614310
TI  - Parkinsonism in phenylketonuria: a consequence of dopamine depletion?
AB  - Phenylketonuria (PKU) is caused by a deficiency or inactivity of the enzyme
      phenylalanine hydroxylase that converts phenylalanine (Phe) to tyrosine (Tyr). It
      has been proposed that a reduction of brain Tyr levels, as well as reduced
      activity of the key regulatory enzyme of dopamine (DA) synthesis tyrosine
      hydroxylase, leads to a depletion in DA activity in patients with PKU. We report
      a case of a 56-year-old woman with an intellectual disability due to late
      diagnosis of PKU and parkinsonism, with a modest clinical response to levodopa
      therapy.We hypothesize that the signs of parkinsonism might be caused by the
      depletion of DA activity in the brain. Clinicians should be alert on parkinsonian
      symptoms in patients with PKU, particularly in those treated with agents that
      negatively influence DA transmission. 

PMID- 25614311
TI  - Long-term functional outcomes of children with hurler syndrome treated with
      unrelated umbilical cord blood transplantation.
AB  - OBJECTIVES: Hurler syndrome is characterized by progressive multisystem
      deterioration leading to early death in childhood. This prospective study
      evaluated the long-term outcomes of patients with Hurler syndrome who underwent
      umbilical cord blood transplantation from unrelated donors. STUDY DESIGN: Only
      patients with Hurler syndrome who underwent umbilical cord blood transplantation
      between December 1995 and March 2006 (n = 25) and who were followed for at least
      5 years (n = 19) were included in the analysis. The patients were longitudinally
      evaluated by a multidisciplinary team of specialists following a standardized
      protocol. RESULTS: Median age at transplantation was 15.9 months (range 2.1-35),
      and patients were followed up until a median age of 10.1 years (range 7.2-14.9).
      Overall survival was 80%. All successfully transplanted patients achieved full
      donor chimerism and normal enzyme levels, and all children continue to make gains
      in development. Gross motor function was the most affected area. Vision and
      hearing were compromised in a minority of the patients, with some requiring
      corneal transplant or hearing aids. Cardiopulmonary function improved. Some
      children required orthopedic surgery, but severe complications were prevented in
      most patients. Although longitudinal growth was lower than that of unaffected
      children, it was considerably higher than expected from the natural course of the
      disease. Head circumference normalized. Hydrocephalus was not observed at longer
      follow-up, and cerebral atrophy decreased over time. CONCLUSIONS: In this
      descriptive study of children with Hurler syndrome, unrelated umbilical cord
      blood transplantation was associated with improved somatic disease and
      neurodevelopment.

PMID- 25614312
TI  - Psychological health in adults with morquio syndrome.
AB  - Mucopolysaccharidosis type IV (MPSIV), also known as Morquio syndrome, is a
      progressive genetic condition which predominantly affects skeletal development.
      Research thus far has focused on physical manifestations, with little attention
      to psychological characteristics. As a first step in determining the natural
      occurrence of psychological symptoms in this population, we administered
      Achenbach measures of psychological functioning (ASEBA ASR and OASR), quality of
      life (SF-36), and pain severity (BPI) questionnaires to 20 adults with Morquio
      syndrome. 11/20 subjects (55%) scored within the symptomatic range on at least
      one or more ASEBA problem scales. These subjects also had higher pain severity
      scores (p = 0.051) and pain interference scores (p = 0.03) on the BPI. However,
      subjects with psychological symptoms did not differ significantly on QOL measures
      from those without psychological symptoms. Overall, subjects scored below the US
      mean only in physical health QOL (p < 0.001) on the SF-36, not mental health QOL.
      Implications of this study include the need for greater attention to
      psychological health in persons with Morquio syndrome, including regular
      assessment for psychological symptoms in addition to the quality of life measures
      typically used, as the latter may miss important information. Greater attention
      to psychological symptoms may help maximize overall health in adults with Morquio
      syndrome. Comparison with psychological studies on other lysosomal storage
      diseases suggests these results may be disease specific, rather than the result
      of living with chronic pain or having an LSD in general. 

PMID- 25614313
TI  - Infection. Double skin protection.
AB  - Skin immunity can be promoted by bacterial skin commensals that induce distinct
      CD8+ T cell responses and by adipocytes that produce antimicrobial peptides.

PMID- 25614317
TI  - T cells. Endogenous agonists for orphan RORgamma.
AB  - Sterol metabolism drives T helper 17 cell differentiation.

PMID- 25614318
TI  - Immune cell promotion of metastasis.
AB  - Metastatic disease is the major cause of death from cancer, and immunotherapy and
      chemotherapy have had limited success in reversing its progression. Data from
      mouse models suggest that the recruitment of immunosuppressive cells to tumours
      protects metastatic cancer cells from surveillance by killer cells, which
      nullifies the effects of immunotherapy and thus establishes metastasis.
      Furthermore, in most cases, tumour-infiltrating immune cells differentiate into
      cells that promote each step of the metastatic cascade and thus are novel targets
      for therapy. In this Review, we describe how tumour-infiltrating immune cells
      contribute to the metastatic cascade and we discuss potential therapeutic
      strategies to target these cells. 

PMID- 25614320
TI  - Cholesterol, inflammation and innate immunity.
AB  - Hypercholesterolaemia leads to cholesterol accumulation in macrophages and other
      immune cells, which promotes inflammatory responses, including augmentation of
      Toll-like receptor (TLR) signalling, inflammasome activation, and the production
      of monocytes and neutrophils in the bone marrow and spleen. On a cellular level,
      activation of TLR signalling leads to decreased cholesterol efflux, which results
      in further cholesterol accumulation and the amplification of inflammatory
      responses. Although cholesterol accumulation through the promotion of
      inflammatory responses probably has beneficial effects in the response to
      infections, it worsens diseases that are associated with chronic metabolic
      inflammation, including atherosclerosis and obesity. Therapeutic interventions
      such as increased production or infusion of high-density lipoproteins may sever
      the links between cholesterol accumulation and inflammation, and have beneficial
      effects in patients with metabolic diseases. 

PMID- 25614319
TI  - Type I interferons in infectious disease.
AB  - Type I interferons (IFNs) have diverse effects on innate and adaptive immune
      cells during infection with viruses, bacteria, parasites and fungi, directly
      and/or indirectly through the induction of other mediators. Type I IFNs are
      important for host defence against viruses. However, recently, they have been
      shown to cause immunopathology in some acute viral infections, such as influenza
      virus infection. Conversely, they can lead to immunosuppression during chronic
      viral infections, such as lymphocytic choriomeningitis virus infection. During
      bacterial infections, low levels of type I IFNs may be required at an early
      stage, to initiate cell-mediated immune responses. High concentrations of type I
      IFNs may block B cell responses or lead to the production of immunosuppressive
      molecules, and such concentrations also reduce the responsiveness of macrophages
      to activation by IFNgamma, as has been shown for infections with Listeria
      monocytogenes and Mycobacterium tuberculosis. Recent studies in experimental
      models of tuberculosis have demonstrated that prostaglandin E2 and interleukin-1
      inhibit type I IFN expression and its downstream effects, demonstrating that a
      cross-regulatory network of cytokines operates during infectious diseases to
      provide protection with minimum damage to the host. 

PMID- 25614321
TI  - Role of innate and adaptive immune mechanisms in cardiac injury and repair.
AB  - Despite the advances that have been made in developing new therapeutics,
      cardiovascular disease remains the leading cause of worldwide mortality.
      Therefore, understanding the mechanisms underlying cardiovascular tissue injury
      and repair is of prime importance. Following cardiac tissue injury, the immune
      system has an important and complex role in driving both the acute inflammatory
      response and the regenerative response. This Review summarizes the role of the
      immune system in cardiovascular disease - focusing on the idea that the immune
      system evolved to promote tissue homeostasis following injury and/or infection,
      and that the inherent cost of this evolutionary development is unwanted
      inflammatory damage. 

PMID- 25614323
TI  - Identifying correlates of self-stigma in adults who stutter: Further establishing
      the construct validity of the Self-Stigma of Stuttering Scale (4S).
AB  - PURPOSE: This study was set up to further establish the construct validity of the
      Self-Stigma of Stuttering Scale (4S) by demonstrating its associations with other
      established scales and replicating its original factor structure and reliability
      estimates. METHOD: Web surveys were completed by 354 adults who stutter recruited
      from Board Certified Specialists in Fluency Disorders, and adult chapters of the
      National Stuttering Association. Participants completed a series of
      psychometrically validated scales measuring self-stigma, hope, empowerment,
      quality of life, social support, anxiety, depression, and self-rated speech
      disruption. RESULTS: Higher subscale and total stigma scores on the 4S were
      associated with significantly lower levels of hope, empowerment, quality of life,
      and social support, and significantly higher levels of anxiety, depression, and
      self-rated speech disruption. The original factor structure of the 4S was
      replicated, and reliability estimates of the subscales ranged from adequate to
      excellent. CONCLUSIONS: The findings of this study support the construct validity
      of the 4S and its use by clinicians and researchers intending to measure the
      construct of self-stigma in adults who stutter. EDUCATIONAL OBJECTIVES: Readers
      should be able to: (a) distinguish between the various components of self-stigma;
      (b) describe how the various components of the self-stigma model relate to hope,
      empowerment, quality of life, and social support, self-rated speech disruption,
      anxiety, and depression; (c) summarize the psychometric properties of the Self
      Stigma of Stuttering Scale (4S) in terms of reliability, factor structure, and
      construct validity; (d) discuss how the 4S could be used in research and clinical
      practice.

PMID- 25614322
TI  - Pharmacogenetics predictive of response and toxicity in acute lymphoblastic
      leukemia therapy.
AB  - Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults
      accounting for no more than 20% of all cases of acute leukemia. By contrast with
      the pediatric population, in whom significant improvements in long term survival
      and even cure have been achieved over the last 30years, adult ALL remains a
      significant challenge. Overall survival in this group remains a relatively poor
      20-40%. Modern research has focused on improved pharmacokinetics, novel
      pharmacogenetics and personalized principles to optimize the efficacy of the
      treatment while reducing toxicity. Here we review the pharmacogenetics of
      medications used in the management of patients with ALL, including l
      asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and
      tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly
      from pediatric ALL, will provide novel perspective of predicting response and
      toxicity in both pediatric and adult ALL therapies. 

PMID- 25614324
TI  - Cognitive, behavioral and goal adjustment coping and depressive symptoms in young
      people with diabetes: a search for intervention targets for coping skills
      training.
AB  - The aim of the present study was to find relevant coping factors for the
      development of psychological intervention programs for young people with Type 1
      (T1) diabetes. A wide range of coping techniques was studied, including cognitive
      coping, behavioral coping and goal adjustment coping. A total of 78 young people
      with T1 diabetes participated. They were contacted through a social networking
      website, several Internet sites, and flyers. A wide range of coping techniques
      appeared to be related to depressive symptoms. Especially the cognitive coping
      strategies self-blame, rumination, refocus positive, and other-blame, together
      with goal adjustment coping, were of importance. A large proportion of the
      variance of depressive symptoms could be explained (65 %). These findings suggest
      that these specific coping strategies should be part of coping skills trainings
      for young people with T1 diabetes. 

PMID- 25614326
TI  - Breaking of a bond: when is it statistical?
AB  - Unimolecular dissociation dynamics of a model three degree of freedom triatomic
      molecule is studied in order to understand the mechanisms for deviations from
      statisticality. Performing a wavelet based time-frequency analysis of the
      dynamics allows for the dynamics to be followed on the network of nonlinear
      resonances, also called as the Arnold web. The results indicate that the long
      lifetime trajectories spend a considerable amount of time trapped near junctions
      in the web. It is argued that characterizing the dynamics near such junctions
      might lead to deeper insights into the origins of nonstatistical dynamics. 

PMID- 25614325
TI  - Parenting an infant with a congenital anomaly: how are perceived burden and
      perceived personal benefits related to parenting stress?
AB  - This study aimed to characterize parents' negative (perceived burden) and
      positive (perceived personal benefits) perceptions about parenting an infant with
      a congenital anomaly (CA), and to investigate their role in parenting stress.
      Forty-three couples (43 mothers and 36 fathers) whose 6-month-old infants had a
      CA completed several questionnaires: the Impact on Family Scale-Revised, the
      Positive Contributions Scale, and the Parenting Stress Index-Short Form. The
      results showed similarities between maternal and paternal perceptions. For
      mothers, higher levels of burden and lower levels of personal benefits were found
      to predict higher levels of parenting stress. For fathers, greater burden was
      associated with higher levels of parenting stress. Some dimensions of personal
      benefits moderated the relationship between burden and parenting stress, for both
      genders. Specific strategies targeting negative and positive perceptions should
      be considered when developing psychological interventions to promote the family's
      adaptation to the experience of parenting an infant with a CA. 

PMID- 25614327
TI  - Tunable pattern-free graphene nanoplasmonic waveguides on trenched silicon
      substrate.
AB  - Graphene has emerged as a promising material for active plasmonic devices in the
      mid-infrared (MIR) region owing to its fast tunability, strong mode confinement,
      and long-lived collective excitation. In order to realize on-chip graphene
      plasmonics, several types of graphene plasmonic waveguides (GPWGs) have been
      investigated and most of them are with graphene ribbons suffering from the
      pattern-caused edge effect. Here we propose a novel nanoplasmonic waveguide with
      a pattern-free graphene monolayer on the top of a nano-trench. It shows that our
      GPWG with nanoscale light confinement, relatively low loss and slowed group
      velocity enables a significant modulation on the phase shift as well as the
      propagation loss over a broad band by simply applying a single low bias voltage,
      which is very attractive for realizing ultra-small optical modulators and optical
      switches for the future ultra-dense photonic integrated circuits. The strong
      light-matter interaction as well as tunable slow light is also of great interest
      for many applications such as optical nonlinearities. 

PMID- 25614328
TI  - The association of abnormal findings on transthoracic echocardiography with 2011
      Appropriate Use Criteria and clinical impact.
AB  - Transthoracic echocardiography (TTE) Appropriate Use Criteria (AUC) were
      developed to promote high-value care. We describe the prevalence of clinically
      significant abnormal TTE findings overall and in subgroups defined by appropriate
      and inappropriate AUC, and their association with clinical impact. 548
      consecutive TTEs at an academic medical center were retrospectively reviewed for
      AUC, clinical impact, and TTE abnormalities. TTE reports within 1 year of the
      index TTE were reviewed to determine if abnormalities were new, unchanged, or
      resolved. Clinical impact was classified into no change, active change, or
      continuation of care. 91% of TTEs were appropriate, 5% were inappropriate, and 4%
      were uncertain by AUC. 46% of all TTEs and 57% of first-time TTEs had no
      significant TTE abnormalities. Appropriate TTEs had a higher prevalence of >=1
      TTE abnormality than inappropriate TTEs (56 vs. 33%, p = 0.029). Among repeat
      TTEs, 72 % had >=1 TTE abnormality, however only 25% had a new abnormality. The
      prevalence of a new abnormality was similar between inappropriate and appropriate
      repeat TTEs (25 vs. 26%, p = 1.0). The prevalence of >=1 abnormality was similar
      between TTEs that resulted in active change and no change in care (70 vs. 64%, p
      = 0.06). Although most TTEs were appropriate as defined by AUC, the majority had
      no significant abnormalities. Although most TTEs were appropriate by AUC, >50% of
      all TTEs and 25% of repeat TTEs had no significant abnormalities. Appropriate
      TTEs had a higher prevalence of abnormalities, however the prevalence of
      abnormalities was similar between TTEs that resulted in active change versus no
      change in care.

PMID- 25614329
TI  - Circumferential vascular strain rate to estimate vascular load in aortic
      stenosis: a speckle tracking echocardiography study.
AB  - Evaluation of vascular mechanics through two-dimensional speckle-tracking (2D-ST)
      echocardiography is a feasible and accurate approach for assessing vascular
      stiffening. Degenerative aortic stenosis (AS) is currently considered a systemic
      vascular disease where rigidity of arterial walls increases. To assess the
      circumferential ascending aorta strain rate (CAASR) in thoracic aortas of
      patients with AS, applying 2D-ST technology. 45 patients with indexed aortic
      valve areas (iAVA) <=0.85 cm(2)/m(2) were studied. Global CAASR served to assess
      vascular deformation. Clinical, echocardiographic, and non-invasive hemodynamic
      data were collected. A follow up (955 days) was also performed. Average age of
      the cohort was 76. +/- 10.3 years, with gender balance. Mean iAVA was 0.43 +/-
      0.15 cm(2)/m(2). Waveforms adequate for determining CAASR were found in 246 (91
      %) of the 270 aortic segments evaluated, for a mean global CAASR of 0.74 +/- 0.26
      s(-1). Both intra- and inter-observer variability of global CAASR were deemed
      appropriate. CAASR correlated significantly with age (r = -0.49, p < 0.01), the
      stiffness index (r = -0.59, p < 0.01), systemic arterial compliance and total
      vascular resistance. There was a significant positive correlation between CAASR,
      body surface area (BSA), iAVA, and a negative relationship with valvulo-arterial
      impedance and E/e' ratio (r = -0.37, p = 0.01). The stiffness index was (beta = 
      0.41, p < 0.01) independently associated with CAASR, in a model adjusted for age,
      BSA, iAVA and E/e'. Patients with a baseline CAASR <=0.66 s(-1) had a worse long
      term outcome (survival 52.4 vs. 83.3 %, Log Rank p = 0.04). CAASR is a promising
      echocardiographic tool for studying the vascular loading component of patients
      with AS.

PMID- 25614330
TI  - Interdependence of right ventricular systolic function and left ventricular
      filling and its association with outcome for patients with pulmonary
      hypertension.
AB  - Although impaired right ventricular (RV) performance has been associated with
      adverse outcomes for pulmonary hypertension (PH) patients, the relationship
      between bi-ventricular interdependence and outcomes is not yet fully understood.
      We studied 96 PH patients. RV systolic function was assessed by means of RV free
      wall longitudinal speckle-tracking strain (RV-free), and left ventricular (LV)
      filling as early diastolic transmitral flow velocity (TMF-E). RV-free <=19 % and
      TMF-E <60 cm/s were adopted as pre-defined cut-offs for RV systolic dysfunction
      and LV under-filling, respectively, associated with worse outcomes. Long-term
      outcome was tracked over 2.2 years. RV-free correlated significantly with TMF-E
      (r = 0.57, p < 0.001).TMF-E and RV-free were significantly lower in patients with
      than in those without cardiac events. RV systolic dysfunction and LV under
      filling was observed in 35 patients. These features were associated with worse
      long-term survival compared to other sub-groups (log-rank p = 0.012). A
      sequential Cox model based on clinical variables including world health
      organization functional class IV and brain natriuretic peptide >150 pg/dl (chi(2)
      = 1.2) was improved by the addition of RV-free (chi(2) = 5.5, p = 0.04) as well
      as of TMF-E (chi(2) = 11.5, p = 0.01). In conclusions, RV systolic function was
      shown to correlate significantly with LV filling in PH patients. In addition, not
      only assessment of RV systolic function, but also of a combined bi-ventricular
      parameter comprising RV systolic function and LV filling may well have clinical
      implications for more successful management of PH patients. 

PMID- 25614331
TI  - Ror2 as a therapeutic target in cancer.
AB  - Ror2 is a signaling receptor for Wnt ligands that is known to play important
      roles in limb development, but having no essential roles known in adult tissues.
      Recent evidence has implicated Ror2 in mediating both canonical and non-canonical
      signaling pathways. Ror2 was initially found to be highly expressed in
      osteosarcoma and renal cell carcinomas, and has recently been found in an
      increasingly long list of cancers currently including melanoma, colon cancer,
      melanoma, squamous cell carcinoma of the head and neck, and breast cancer. In the
      majority of these cancer types, Ror2 expression is associated with more
      aggressive disease states, consistent with a role mediating Wnt signaling
      regardless of the canonical or noncanonical signal. Because of the pattern of
      tissue distribution, the association with high-risk diseases, and the cell
      surface localization of this receptor, Ror2 has been identified as a potential
      high value target for therapeutic development. However, the recent discovery that
      Ror2 may function through non-kinase activities challenges this strategy and
      opens up opportunities to target this important molecule through alternative
      means.

PMID- 25614332
TI  - Different CT perfusion algorithms in the detection of delayed cerebral ischemia
      after aneurysmal subarachnoid hemorrhage.
AB  - INTRODUCTION: Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP)
      result in an overestimation of the extent of ischemia in thromboembolic stroke.
      In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid
      hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also
      overestimate the extent of ischemia. We investigated the diagnostic accuracy of
      tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI.
      METHODS: From a prospectively collected series of aSAH patients admitted between
      2007-2011, we included patients with any clinical deterioration other than
      rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of
      clinical deterioration were categorized into DCI and no DCI. CTP maps were
      calculated with tracer delay-sensitive and tracer delay-insensitive algorithms
      and were visually assessed for the presence of perfusion deficits by two
      independent observers with different levels of experience. The diagnostic value
      of both algorithms was calculated for both observers. RESULTS: Seventy-one
      patients were included. For the experienced observer, the positive predictive
      values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay
      insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and
      0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and
      NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive
      algorithm. CONCLUSION: Test characteristics are comparable for tracer delay
      sensitive and tracer delay-insensitive algorithms for the visual assessment of
      CTP in diagnosing DCI. This indicates that both algorithms can be used for this
      purpose.

PMID- 25614333
TI  - Large anterior temporal Virchow-Robin spaces: unique MR imaging features.
AB  - INTRODUCTION: Large Virchow-Robin (VR) spaces may mimic cystic tumor. The
      anterior temporal subcortical white matter is a recently described preferential
      location, with only 18 reported cases. Our aim was to identify unique MR features
      that could increase prospective diagnostic confidence. METHODS: Thirty-nine cases
      were identified between November 2003 and February 2014. Demographic, clinical
      data and the initial radiological report were retrospectively reviewed. Two
      neuroradiologists reviewed all MR imaging; a neuropathologist reviewed
      histological data. RESULTS: Median age was 58 years (range 24-86 years); the
      majority (69 %) was female. There were no clinical symptoms that could be
      directly referable to the lesion. Two thirds were considered to be VR spaces on
      the initial radiological report. Mean maximal size was 9 mm (range 5-17 mm);
      majority (79 %) had perilesional T2 or fluid-attenuated inversion recovery
      (FLAIR) hyperintensity. The following were identified as potential unique MR
      features: focal cortical distortion by an adjacent branch of the middle cerebral
      artery (92 %), smaller adjacent VR spaces (26 %), and a contiguous cerebrospinal
      fluid (CSF) intensity tract (21 %). Surgery was performed in three asymptomatic
      patients; histopathology confirmed VR spaces. Unique MR features were
      retrospectively identified in all three patients. CONCLUSION: Large anterior
      temporal lobe VR spaces commonly demonstrate perilesional T2 or FLAIR signal and
      can be misdiagnosed as cystic tumor. Potential unique MR features that could
      increase prospective diagnostic confidence include focal cortical distortion by
      an adjacent branch of the middle cerebral artery, smaller adjacent VR spaces, and
      a contiguous CSF intensity tract.

PMID- 25614334
TI  - Inhibition of P2Y6 receptor-mediated phospholipase C activation and Ca(2+)
      signalling by prostaglandin E2 in J774 murine macrophages.
AB  - Extracellular nucleotides act as inflammatory mediators through activation of
      multiple purinoceptors. Under inflammatory conditions, the purinergic signalling
      is affected by various inflammatory mediators. We previously showed that
      prostaglandin (PG) E2 suppressed the elevation of intracellular Ca(2+)
      concentration ([Ca(2+)]i) stimulated by P2X4, P2Y2, and P2Y6 receptors in J774
      murine macrophages. In this study, we examined the mechanism of PGE2 inhibitory
      effects on P2Y6 receptor-mediated function in J774 cells. The P2Y6 receptor
      agonist UDP induced a sustained elevation of [Ca(2+)]i by stimulating the
      phospholipase C (PLC) signalling pathway. PGE2 inhibited [Ca(2+)]i elevation and
      phosphatidylinositol (PI) hydrolysis in a concentration-dependent manner. J774
      cells highly expressed the E-type prostanoid 2 (EP2) receptor subtype, a Gs
      coupled receptor. PGE2 and a selective EP2 receptor agonist caused cyclic AMP
      (cAMP) accumulation in J774 cells. The inhibitory effects of PGE2 on P2Y6
      receptor-mediated responses were mimicked by the selective EP2 receptor agonist.
      Although EP2 receptor is linked to adenylyl cyclase activation, PGE2-induced
      inhibition of Ca(2+) response and PI hydrolysis could not be mimicked by a
      lipophilic cAMP derivative, dibutyryl cAMP, or an adenylyl cyclase activator,
      forskolin. The inhibition of UDP-induced PLC activation by PGE2 was not affected
      by down-regulation of protein kinase C by phorbol-12-myristate-13-acetate
      treatment. PGE2 inhibited PLC activation induced by aluminium fluoride, but not
      by the Ca(2+)-ionophore, ionomycin. Finally, the inhibition of UDP-induced PLC
      activation by PGE2 was impaired by Gs knockdown using siRNA. These results
      suggest that EP2 receptor activation in macrophages negatively controls the Gq/11
      PLC signalling through a Gs-mediated, but cAMP-independent signalling mechanism. 

PMID- 25614335
TI  - Cyclophilin D-mediated apoptosis attributes to sorafenib-induced cytotoxicity in
      clear cell-renal cell carcinoma.
AB  - Cyclophilin D (CypD) is an essential regulatory component of the mitochondrial
      permeability transition pore (MPTP) and mediates cell necrosis. The aim of this
      study was to assess the effects of the multi-target drug, sorafenib, on clear
      cell-renal cell carcinoma (ccRCC) necrosis by regulating CypD expression and to
      explore whether this effect was related to the phosphorylation of extracellular
      signal-regulated kinases (ERKs). We used immunohistochemical analysis to compare
      CypD and p-ERK expression in human ccRCC tissues (n=53) and adjacent non
      cancerous tissues (ANCT, n=34). CypD expression was localized to the cytoplasm of
      renal tubular epithelial cells and was lower in ccRCC samples while p-ERK
      expression was higher in ccRCC samples. In the in vitro assay, CypD was
      downregulated in ccRCC cell lines 786-O and A498 as compared with HK-2 which is a
      normal human renal tubular epithelial cell line. Overexpression of CypD induced
      the apoptosis of 786-O and A498 cells. Sorafenib induced the apoptosis of 786-O
      cells, which was coupled with the upregulation of CypD. Cyclosporin A (CsA, the
      inhibitor of CypD) and CypD siRNA inhibited the effect of sorafenib on apoptosis
      induced 786-O and mitochondrial membrane potential depolarization. Epidermal
      growth factor (EGF, the activator of ERK) and ERK overexpression inhibited the
      effect of sorafenib on CypD expression, apoptosis-induced 786-O and mitochondrial
      membrane potential depolarization. In conclusion, our results suggested that CypD
      may represent a new therapeutic target for the treatment of ccRCC. Sorafenib
      induced apoptosis in ccRCC through CypD upregulation and this effect was related
      to the inhibition of p-ERK. 

PMID- 25614336
TI  - Cardiac function changes with switching from the supine to prone position:
      analysis by quantitative semiconductor gated single-photon emission computed
      tomography.
AB  - BACKGROUND: Prone positioning is required in certain operations such as spinal
      surgery. Changes in cardiac function in the prone position have been studied with
      various methodologies. Few studies have investigated changes in left ventricular
      diastolic function and rhythm in subjects turned prone. METHODS AND RESULTS:
      Cardiac function was evaluated in the supine and prone positions in 90 patients
      without atrial fibrillation who underwent (99m)Tc-tetrofosmin quantitative gated
      single-photon emission computed tomography. Three groups of 30 patients each were
      classified as "no history of myocardial ischemia or cardiomyopathy" (Group A),
      "history of myocardial infarction" (Group B), and "ischemic heart disease without
      myocardial infarction history" (Group C). Upon assuming the prone position, the
      cardiac index and any dyssynchrony worsened in all groups. Ejection fraction
      changes occurred only in Group B, and diastolic function changes occurred in
      Groups B and C, but not in Group A. The changes caused by prone positioning were
      more severe in the patients with poor cardiac function. CONCLUSIONS: Prone
      positioning induces significant changes in systolic and diastolic function, as
      well as dyssynchrony. The negative effects of prone positioning are more severe
      in patients with poor baseline cardiac function.

PMID- 25614337
TI  - A potential explanation for lower minor complication rate for lead extraction in
      high-volume centres.

PMID- 25614338
TI  - Lesion formation after pulmonary vein isolation using the advance cryoballoon and
      the standard cryoballoon: lessons learned from late gadolinium enhancement
      magnetic resonance imaging.
AB  - AIMS: To compare ablation lesion formation after pulmonary vein isolation (PVI)
      using the standard cryoballoon (CB-S) vs. the re-designed cryoballoon Arctic
      Front Advance (CB-A) using late gadolinium enhancement magnetic resonance imaging
      (LGE-MRI) 3 months post-ablation. METHODS AND RESULTS: Thirty-six consecutive
      patients with paroxysmal or short-lasting persistent atrial fibrillation (AF)
      were evaluated prospectively after PVI using the CB-S in the first 18 patients
      and the CB-A in the subsequent 18 patients. All patients underwent LGE-MRI and a
      7-day Holter electrocardiogram monitoring 3 months after ablation. Fifty-six per
      cent of the patients were male (mean age 63.0 +/- 9.1 years). Fifty-six per cent
      in the first group and 89% in the second group were free of AF recurrence 3
      months after ablation (P = 0.025). Three months after ablation, LGE-MRI of the
      left atrium showed complete circular lesions in 35% of PVs in the first group and
      in 32% of PVs in the second group (n.s.). The left PVs showed a significantly
      higher proportion of PV segments with complete ablation lesions compared with the
      right PVs (83 vs. 34%; P < 0.001). CONCLUSION: Cardiac MRI is able to visualize
      induced ablation lesions after PVI and might be suitable to quantify ablation
      lesion amount. Ablation lesion formation did not differ significantly in patients
      treated with the CB-S vs. the CB-A, despite a significantly lower rate of AF
      recurrence after 3 months in the CB-A group. Left PVs showed a significantly
      higher amount of ablation lesions compared with the right PVs. Larger and
      randomized studies are needed to understand the relationship between
      representable tissue lesions and success rates.

PMID- 25614339
TI  - Relationship between exposure to fine particulates and ozone and reduced lung
      function in children.
AB  - BACKGROUND: A limited number of studies have reported an association between long
      term exposure to ambient air pollutants and lung function growth among children,
      with inconclusive results. OBJECTIVES: To assess the relationship between air
      pollutant exposure and lung function growth, and to examine potential sex
      differences in the susceptibility of lung function growth to air pollution.
      METHODS: We conducted a two-year prospective cohort study of Taiwanese children
      aged 12 at baseline who were followed from October 1, 2007 to November 31, 2009.
      The study population comprised 2941 non-smoking children who completed pulmonary
      function tests at both baseline and follow-up surveys. We applied spatial
      modeling for individual-level exposure assessment to capture relevant exposures
      and also attempted to eliminate potential community-level confounding. The
      exposure parameters were annual averages and values calculated from 24-hourly
      PM2.5 and 8-hourly ozone (O3) concentrations, corresponding to the residential
      addresses over the study period. The effect estimates were presented as lung
      function growth deficits per interquartile range (IQR) for PM2.5 and O3. RESULTS:
      In a multiple linear mixed effect model, adjusted for confounding, growth
      deficits in the forced vital capacity (FVC), forced expiration volume in 1s
      (FEV1), and forced expiratory flow between the 25th and 75th percentiles of the
      FVC were associated with increased exposure to PM2.5 and O3. For example, greater
      exposure to PM2.5 (IQR, 17.92MUg/m(3)) was associated with an annual deficit in
      FVC growth of 75mL in boys and 61mL in girls (p for interaction <0.05). Similar
      associations were found for O3. CONCLUSIONS: The study provides evidence that
      long-term exposure to PM2.5 and O3 may have a detrimental effect on the
      development of lung function in children. The estimated deficits were generally
      larger in boys, compared to girls.

PMID- 25614340
TI  - Predicting cytotoxicity of complex mixtures in high cancer incidence regions of
      the Huai River Basin based on GC-MS spectrum with partial least squares
      regression.
AB  - Complex mixture exposures, such as those associated with water sources, are an
      important issue in health risk assessment. This study assessed the cytotoxicity
      of chemical mixtures extracted from water sources in regions of the Huai River
      Basin with high cancer incidences and built statistical models of cytotoxicity
      based on pollution profiles that were measured with gas chromatography-mass
      spectrometry (GC-MS). Both surface and ground waters were collected from rural
      water sources of Shenqiu County, Henan Province of China from 2008 to 2011 and
      extracted with XAD-2 resigns. Cytotoxicity was evaluated with Chinese hamster
      ovary K1 (CHO-K1) cells and compared against the pollution profiles of the
      extracts. IC50 of water samples ranged from 0.023 to 0.338L-eq/mL. The pollutants
      in waters determined by GC-MS are complex and some of the compounds that
      contributed to cytotoxicity lack toxicity data. A partial least squares (PLS)
      regression model of cytotoxicity was built based on linear aggregation of
      predictor variables (i.e., peaks for single compounds in the gas chromatograms).
      The PLS model contains 2 PLS factors extracted from 141 variables. The model was
      validated internally with training data permutation and externally with a test
      sample. The model explained 92% of the cytotoxicity in the training samples and
      40% in the test sample. This approach provides a general, rapid method for
      relating water toxicity to GC-MS chromatograms and for predicting the compounds
      that contribute most to toxicity. 

PMID- 25614341
TI  - X-ray imaging characterization of femoral bones in aging mice with osteopetrotic
      disorder.
AB  - Aging mice with a rare osteopetrotic disorder in which the entire space of
      femoral bones are filled with trabecular bones are used as our research platform.
      A complete study is conducted with a micro computed tomography (CT) system to
      characterize the bone abnormality. Technical assessment of femoral bones includes
      geometric structure, biomechanical strength, bone mineral density (BMD), and bone
      mineral content (BMC). Normal aging mice of similar ages are included for
      comparisons. In our imaging work, we model the trabecular bone as a cylindrical
      rod and new quantitative which are not previously discussed are developed for
      advanced analysis, including trabecular segment length, trabecular segment
      radius, connecting node number, and distribution of trabecular segment radius. We
      then identified a geometric characteristic in which there are local maximums
      (0.0049, 0.0119, and 0.0147 mm) in the structure of trabecular segment radius.
      Our calculations show 343% higher in percent trabecular bone volume at distal
      metaphysis; 38% higher in cortical thickness at mid-diaphysis; 11% higher in
      cortical cross-sectional moment of inertia at mid-diaphysis; 42% higher in
      cortical thickness at femur neck; 26% higher in cortical cross-sectional moment
      of inertia at femur neck; 31% and 395% higher in trabecular BMD and BMC at distal
      metaphysis; 17% and 27% higher in cortical BMD and BMC at distal-metaphysis; 9%
      and 53% higher in cortical BMD and BMC at mid-diaphysis; 25% and 64% higher in
      cortical BMD and BMC at femur neck. Our new quantitative parameters and findings
      may be extended to evaluate the treatment response for other similar bone
      disorders.

PMID- 25614342
TI  - Patient satisfaction from two studies of collaborative doctor-pharmacist
      prescribing in Australia.
AB  - BACKGROUND: Pharmacist prescribing has been introduced in several countries and
      is a possible future role for pharmacy in Australia. OBJECTIVE: To assess whether
      patient satisfaction with the pharmacist as a prescriber, and patient experiences
      in two settings of collaborative doctor-pharmacist prescribing may be barriers to
      implementation of pharmacist prescribing. DESIGN: Surveys containing closed
      questions, and Likert scale responses, were completed in both settings to
      investigate patient satisfaction after each consultation. A further survey
      investigating attitudes towards pharmacist prescribing, after multiple
      consultations, was completed in the sexual health clinic. SETTING AND
      PARTICIPANTS: A surgical pre-admission clinic (PAC) in a tertiary hospital and an
      outpatient sexual health clinic at a university hospital. Two hundred patients
      scheduled for elective surgery, and 17 patients diagnosed with HIV infection,
      respectively, recruited to the pharmacist prescribing arm of two collaborative
      doctor-pharmacist prescribing studies. RESULTS: Consultation satisfaction
      response rates in PAC and the sexual health clinic were 182/200 (91%) and 29/34
      (85%), respectively. In the sexual health clinic, the attitudes towards
      pharmacist prescribing survey response rate were 14/17 (82%). Consultation
      satisfaction was high in both studies, most patients (98% and 97%, respectively)
      agreed they were satisfied with the consultation. In the sexual health clinic,
      all patients (14/14) agreed that they trusted the pharmacist's ability to
      prescribe, care was as good as usual care, and they would recommend seeing a
      pharmacist prescriber to friends. DISCUSSION AND CONCLUSION: Most of the patients
      had a high satisfaction with pharmacist prescriber consultations, and a positive
      outlook on the collaborative model of care in the sexual health clinic.

PMID- 25614344
TI  - The use of glucocorticoids in marmoset wasting syndrome.
AB  - BACKGROUND: Marmoset wasting syndrome (MWS) is one of the leading causes of
      morbidity and mortality in captive marmosets, and thus far no reliable treatment
      has been found. Glucocorticoids are used widely to treat inflammatory conditions
      of the GI tract such as human and feline inflammatory bowel disease, which, such
      as MWS, are histologically characterized by chronic lymphoplasmacytic
      inflammation in the intestines. Budesonide is a glucocorticoid with few reported
      side effects due to the majority of it being metabolized into inactive compounds
      by the liver before entering the systemic circulation. METHOD: Eleven marmosets
      presented with antemortem signs consistent with MWS and were treated with oral
      prednisone or budesonide for 8 weeks. RESULTS: The marmosets in our study
      demonstrated a significant increase in both weight and albumin levels (relative
      to pre-treatment values) after glucocorticoid therapy. CONCLUSIONS:
      Glucocorticoids are an effective therapy to ameliorate the clinical signs
      associated with MWS with minimal side effects.

PMID- 25614345
TI  - Coxalgia? Call the gynecologist.
AB  - Cellular angiofibroma is a rare mesenchymal tumor that usually affects the vulvar
      region. It is commonly asymptomatic and treated with radical excision. We
      describe the first case of cellular angiofibroma located in the retroperitoneum
      presenting with coxalgia and laparoscopically treated. At the 6-month follow-up,
      the patient was coxalgia and disease free. Coxalgia is an unusual symptom for
      gynecologists; nevertheless, it is possible that several neoplasms may originate
      in the female pelvis, so any symptom requires careful evaluation. The
      laparoscopic approach may be effective in removing cellular angiofibroma,
      avoiding injuries to surrounding structures and unesthetic scarring and leading
      to a faster recovery. 

PMID- 25614346
TI  - Learning Curve Analysis and Surgical Outcomes of Single-port Laparoscopic
      Myomectomy.
AB  - STUDY OBJECTIVE: To identify learning curves for single-port laparoscopic
      myomectomy (SPLM) and evaluate surgical outcomes according to the sequence of
      operation. DESIGN: A retrospective study. SETTING: A university-based hospital
      (Canadian Task Force classification II-2). PATIENTS: The medical records from 205
      patients who had undergone SPLM from October 2009 to May 2013 were reviewed.
      Because the myomectomy time was significantly affected by the size and number of
      myomas removed by SPLM, cases in which 2 or more of the myomas removed were >7 cm
      in diameter were excluded. Furthermore, cases involving additional operations
      performed simultaneously (e.g., ovarian or hysteroscopic surgery) were also
      excluded. A total of 161 cases of SPLM were included. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We assessed the SPLM learning curve via a graph
      based on operation time versus sequence of cases. Patients were chronologically
      arranged according to their surgery dates and were then placed into 1 of 4 groups
      according to their operation sequence. SPLM was completed successfully in 160 of
      161 cases (99.4%). One case was converted to multiport surgery. Basal
      characteristics of the patients between the 4 groups did not differ. The median
      operation times for the 4 groups were 112.0, 92.8, 83.7, and 90.0 minutes,
      respectively. Operation time decreased significantly in the second, third, and
      fourth groups compared with that in the first group (p < .001). Proficiency,
      which is the point at which the slope of the learning curve became less steep,
      was evident after about 45 operations. CONCLUSION: Results from the current study
      suggested that proficiency for SPLM was achieved after about 45 operations.
      Additionally, operation time decreased with experience without an increase in
      complication rate.

PMID- 25614347
TI  - A large, nationwide, longitudinal study of central nervous system diseases among
      Korean workers exposed to manganese.
AB  - INTRODUCTION: In occupational epidemiologic studies, the low incidence and
      chronic process of central nervous system (CNS) diseases has complicated the
      determination of the relationship between increased morbidity and manganese (Mn)
      exposure. Therefore, through this large cohort study, we evaluated CNS disease
      morbidity among Korean workers exposed to Mn METHODS: Data were collected from Mn
      associated specialized medical check-up 2000 and 2004 in Korea. The number of
      workers admitted to hospital because of clinically diagnosed CNS disease was
      analyzed in male workers exposed to Mn (n = 104,544). As a control reference
      population, 2% of Korean men were randomly selected and their hospital admission
      data were analyzed. For Mn-exposed workers, Standardized admission ratios (SARs)
      for CNS disease, as determined by ICD-10 classifications, were estimated in
      reference to the control population RESULTS: During follow up, 64 workers
      admitted because of CNS diseases. Chronic exposure to Mn (>= 10 years) was
      significantly associated with the SAR (95% CI) of extrapyramidal and movement
      disorders (SAR: 2.03, 95% CI: 1.05-3.55), in particular, other extrapyramidal and
      movement disorders (SAR: 4.81, 95% CI: 1.29-12.32). Also borderline association
      (SAR = 4.88, 90% CI: 1.05-7.04) was noted for secondary Parkinsonism among
      workers with chronic Mn exposure. SARs (95% CI) for other degenerative nervous
      system diseases were significantly higher in Mn-exposed workers compared with the
      control population (SAR: 3.60, 95% CI: 1.16-8.40) CONCLUSION: In conclusion, Mn
      exposed workers exhibited significantly elevated SARs for degenerative nervous
      system diseases and extrapyramidal and movement disorders, compared to the age
      matched reference population, suggesting a relatedness with Mn exposure.

PMID- 25614348
TI  - [Papillary edema in Muckle-Wells syndrome].
AB  - Papillary edema may occur isolated without functional impairment or secondary
      related to various syndromes, increased intracerebral pressure or associated with
      medicinal treatment. The Muckle-Wells syndrome is a rare disease, which among
      many other symptoms can lead to optic disc swelling and recurrent increase in
      intracerebral pressure. Besides familial cold-induced autoinflammatory syndrome
      (FCAS) and neonatal onset multisystem inflammatory disease (NOMID), the Muckle
      Wells syndrome also belongs to the cryopyrin-associated periodic syndromes
      (CAPS). In most cases of CAP syndromes there is an underlying genetic disorder
      that leads to overproduction of interleukin-1beta (IL-1beta); therefore, typical
      symptoms include inflammation reactions, such as repeated skin rash, fatigue,
      fever, joint pain and conjunctivitis.

PMID- 25614349
TI  - [Special aspects of pediatric anesthesia in ophthalmic surgery].
AB  - In ophthalmic surgery, children are anesthetized for various reasons. The airway
      needs special attention as children have higher oxygen requirements and brief
      periods of apnea can result in hypoxemia and subsequent bradycardia or even
      cardiac arrest. Most interventions can be managed with the aid of a laryngeal
      mask allowing minor airway manipulations and thereby reducing the risk of
      laryngeal and tracheal injuries and laryngospasm in children with hypersensitive
      airways. In children older than 3 years an adequate postoperative nausea and
      vomiting (PONV) prophylaxis should be performed. The modified postoperative
      vomiting in children (POVOC) score is a suitable method for the estimation of
      PONV. Strabismus surgery is an independent risk factor for PONV; therefore,
      prophylaxis is recommended in any case. The combination of drugs from different
      substance groups amplifies the antiemetic effect. This article discusses whether
      anesthesia can damage immature brains. In animal experiments it could be proven
      that neuronal apoptosis could be induced by most of the commonly used
      anesthetics. It has not yet been clarified whether this has an effect on the
      neurocognitive development of children. Because of this uncertainty the
      indications for surgery and anesthesia should be assessed on strict clinical
      requirements. There is, however, widespread agreement that a necessary anesthesia
      carried out in a correct and controlled manner has no negative consequences for
      children. 

PMID- 25614350
TI  - Self-healing polymer materials constructed by macrocycle-based host-guest
      interactions.
AB  - Self-healing polymers, which can spontaneously recover themselves after being
      ruptured, result in enhanced lifetimes for materials and open up a fascinating
      direction in material science. Macrocycle-based host-guest interactions, one of
      the most crucial non-covalent interactions, play a key role in self-healing
      material fabrication. This review aims to highlight the very recent and important
      progress made in the area of self-healing polymer materials by focusing on
      cyclodextrins (CDs), crown ethers, cucurbit[n]urils (CBs), calix[n]arenes and
      pillar[n]arenes with special guest groups and tailored structures. In addition,
      we also propose future research directions and hope that this review can in a way
      reflect the current situation and future trends in this developing area. 

PMID- 25614351
TI  - Scheduled intravenous acetaminophen reduces postoperative narcotic analgesic
      demand and requirement after laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Intravenous (i.v.) acetaminophen has the potential to reduce
      postoperative narcotic analgesic requirement but this has not been reported in
      bariatric surgery. As lower dosages could reduce undesirable narcotic side
      effects, we investigated the opioid-sparing effect of concomitant i.v.
      acetaminophen in bariatric surgery. METHODS: We performed a retrospective review
      of our electronic medical records of laparoscopic Roux-en-Y gastric bypasses
      (LRYGB) performed for severe obesity between 2011 and 2013. We identified 183
      patients that received scheduled i.v. acetaminophen in addition to morphine
      sulfate (MSO4) patient-controlled analgesia (PCA). A cohort of 229 patients from
      the preceding 2 years who were treated with MSO4 PCA but not acetaminophen was
      used as a historical control. Patient demographic characteristics and narcotic
      use data were extracted from electronic medical records. Student's t test or
      linear regression was used as appropriate (P< .05). RESULTS: During the first 24
      hour postoperative period after LRYGB, narcotic analgesic demand (total PCA
      demand including nondelivery of narcotic due to lock-out) was reduced by 25% with
      the concomitant use of i.v. acetaminophen (40.5 versus 30.9 average pushes;
      P<.05). During the same period, narcotic analgesic dosage requirement was cut
      down by 20% in the study group (average of 29.9 versus 24.1 mg of MSO4; P<.05).
      Linear regression analysis confirmed that these changes were independent of age,
      gender, and body mass index distribution, or type 2 diabetes mellitus.
      CONCLUSION: Scheduled i.v. acetaminophen reduces the demand for and the
      requirement of narcotic analgesia after LRYGB. We provide new evidence in support
      of the routine use of multimodal analgesia that includes scheduled i.v.
      acetaminophen in the initial 24-hour period after bariatric surgery.

PMID- 25614352
TI  - Five-year results after laparoscopic sleeve gastrectomy: a prospective study.
AB  - BACKGROUND: Whilst the early to mid-term efficacy of laparoscopic sleeve
      gastrectomy (SG) is well established, there is comparatively less detailing of
      long-term efficacy. The objectives of this study were to evaluate the long-term
      outcomes of patients undergoing SG at the authors' institution. METHODS: All
      patients undergoing SG during the past 5 or more years were eligible. Outcomes
      included baseline demographic data, preoperative characteristics, percentage
      excess weight loss (%EWL), co-morbidity improvement and resolution, serum
      hemoglobin A(1c) (HbA(1c)), serum lipid profile, and the Bariatric Analysis
      Reporting Outcome System (BAROS) questionnaire. A subset analysis was also
      performed with patients stratified in to super obese (body mass index >= 50
      kg/m(2)). RESULTS: There were 96 patients who underwent surgery between March
      2007 and July 2008. Of these, 10 declined to participate, 28 were unable to be
      contacted, and 3 were deceased; therefore, 55 patients were included in the
      analysis. The mean yearly %EWL to postoperative year 5 was 56% (year 1), 55%
      (year 2), 46% (year 3), 43% (year 4), and 40% (year 5). Combined improvement and
      resolution rates at 5 years were 79%, 61%, and 73% for type 2 diabetes,
      hypertension, and obstructive sleep apnea, respectively. The HbA(1c) was
      significantly reduced at long-term follow-up. The mean BAROS score was 3.13 (95%
      CI: 2.4, 3.9). Weight loss outcomes were less favorable in super obese patients.
      CONCLUSION: Weight loss outcomes at 5 year follow-up were modest after SG though
      improvement in co-morbidity status was maintained.

PMID- 25614353
TI  - Safety of one-step conversion of gastric band to sleeve: a comparative analysis
      of ACS-NSQIP data.
AB  - BACKGROUND: The conversion rate of laparoscopic adjustable gastric banding (LAGB)
      to laparoscopic sleeve gastrectomy (LSG) has increased during recent years. The
      safety profile of one-step conversion of LAGB to LSG is not clear from the
      current literature. METHODS: Using the database of the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), morbidly
      obese patients undergoing primary LSG and conversion of LAGB to LSG in one-step
      between 2010 and 2012 were identified. Perioperative outcomes (including 30-day
      composite rate comprised of 18 postoperative adverse events) were compared
      between groups using a univariate cross-sectional analysis. RESULTS: Data of
      11,320 patients (10,997 primary LSG and 323 LAGB to LSG) were analyzed. The LAGB
      to-LSG group had better preoperative health status, including significantly lower
      body mass index, American Society of Anesthesiologists scores, and prevalence of
      diabetes and hypertension. Operative time for the LAGB-to-LSG group (130.0+/-53.7
      min) was significantly longer than primary LSG group (98.5+/-42.8 min, P<.001).
      The 30-day composite adverse event rate was 6.8% in the LAGB-to-LSG group and
      5.4% in the primary LSG group (P = .29). The rate of minor complications,
      including urinary tract infection and wound infection were significantly higher
      in the revisional surgery group. Thirty-day rates of other postoperative
      complications, reoperation, readmission, mortality, and length of hospital stay
      were comparable between the 2 groups. CONCLUSIONS: This national data suggests
      that conversion of LAGB to LSG in a single stage has comparable safety to primary
      LSG. In this study, improved preoperative health status of patients in the
      revisional group may serve as an equalizer with regards to postoperative outcomes
      of conversion to LSG.

PMID- 25614354
TI  - Laparoscopic sleeve gastrectomy as day-case surgery (without overnight
      hospitalization).
AB  - BACKGROUND: Day-case surgery (DCS) has boomed over recent years, as has
      laparoscopic sleeve gastrectomy (SG) for the treatment of morbid obesity. The
      objective of this study was to evaluate the safety and feasibility of day-case
      SG. METHODS: This was a prospective, nonrandomized study of 100 patients
      undergoing day-case SG from May 2011 to July 2013. All patients met the criteria
      for DCS and for the treatment of morbid obesity. Standard surgical, anesthetic,
      and analgesic protocols were used. The primary study endpoint was the unplanned
      overnight admission rate. Secondary endpoints were standard DCS criteria,
      frequency and type of complications, and satisfaction rate of performing day-case
      SG. The short-term postoperative course of patients undergoing day-case and
      conventional SG also were compared. RESULTS: A total of 416 patients were
      screened and 100 (24%) were included. There were 8 unplanned overnight
      admissions. Seven unexpected consultations, 7 hospital readmissions, and 5 major
      complications were recorded, including 3 cases of unexpected surgery for gastric
      leak. At follow-up, 96% of the patients were satisfied with day-case SG. The
      short-term postoperative course was similar among patients undergoing DCS and
      conventional management. CONCLUSION: In selected patients, day-case SG is
      feasible with acceptable complication and readmission rates. The postoperative
      course was similar to that observed for standard SG.

PMID- 25614355
TI  - Comment on: Assessment of the quality of Internet information on sleeve
      gastrectomy.

PMID- 25614356
TI  - Single anastomosis or mini-gastric bypass: long-term results and quality of life
      after a 5-year follow-up.
AB  - BACKGROUND: Laparoscopic mini-gastric bypass (LMGB) is an alternative to the
      laparoscopic Roux-en-Y gastric bypass (LRYGB), which is considered to be the gold
      standard in the treatment of morbid obesity. OBJECTIVES: Present 5-year results
      of 175 patients who had undergone a LMGB between October 2006 and October 2008.
      SETTING: University public hospital, France. METHODS: Complete follow-up was
      available in 126 of 175 patients (72%) who had LMGB. Mortality, morbidity, weight
      loss, co-morbidities, and quality of life were assessed. Weight loss was
      determined as a change in body mass index (BMI) and percent excess BMI loss
      (%EBMIL). Quality of life in the treatment group was analyzed using the
      Gastrointestinal Quality of Life Index (GIQLI) and was compared with a
      retrospectively case matched preoperative control group. RESULTS: There were no
      deaths. Thirteen patients (10.3%) developed major complications. Marginal ulcers
      occurred in 4% of patients. Incapacitating biliary reflux developed in 2 (1.6%)
      who required conversion into RYGB. Gastric pouch dilation occurred in 4 patients
      (3.2%) and inadequate weight loss with severe malnutrition in 2 (1.6%). At 5
      years, mean BMI was 31+/-6 kg/m(2) and mean %EBMIL was 71.5%+/-26.5%.
      Postoperative GIQLI score of the treatment group was significantly higher than
      preoperative score of the control group (110.3+/-17.4 versus 92.5+/-15.9,
      P<.001). Social, psychological, and physical functions were increased
      significantly. No significant differences were found in gastroesophageal reflux
      or diarrhea symptoms between the 2 groups. Long-term follow-up showed an
      improvement in all co-morbidities. CONCLUSIONS: At 5 years, LMGB was safe,
      effective, and provided interesting quality of life results.

PMID- 25614357
TI  - Bowel length: measurement, predictors, and impact on bariatric and metabolic
      surgery.
AB  - BACKGROUND: Small bowel length (SBL) determines the caloric absorptive capacity.
      The aim of this study was to evaluate SBL to identify patient-specific predictors
      and the interrelationships of SBL with anthropometric variables. METHODS: Sex,
      age, and weight were recorded at the time of surgery when SBL and the estimated
      jejunal length (JLe) were measured by 3 different methods. RESULTS: The mean SBL
      of 443 patients undergoing laparotomy (78% female) was 690+/-93.7 cm (range 350
      1049 cm). Sex was correlated with SBL, as men had a longer small bowel than women
      (729+/-85 versus 678+/-92, P<.0001) and were significantly taller (173+/-8.2
      versus 161+/-6.9, P<.001). Age did not correlate with SBL. The differences in
      length between fully stretched small bowel and nonstretched small bowel and
      between fully stretched small bowel and laparoscopic bowel were 137+/-19 cm and
      32.4+/-11.4 cm, respectively. In a multivariate linear regression analysis model
      that included sex, age, height, and weight, only height was significantly
      correlated with SBL (P<.00001) and explained 12% of the variance in SBL. Sex,
      age, height, and JLe, but not SBL, were statistically highly significant in
      predicting 75% of the variance of body weight. CONCLUSIONS: A positive
      association between height and SBL was found. Sex, age, height, and JLe may be
      strong predictors of weight. Individual JLe may be of importance in determining
      the weight loss and resolution of metabolic co-morbidities. Measuring the SBL can
      prevent the risk of nutritional consequences in malabsorptive, revisional, and
      metabolic procedures.

PMID- 25614358
TI  - Inefficacy of vancomycin and teicoplanin in eradicating and killing
      Staphylococcus epidermidis biofilms in vitro.
AB  - Biofilm-associated bacteria display a decreased susceptibility towards
      antibiotics. Routine assessment of antibiotic susceptibility of planktonic
      bacteria therefore offers an insufficient prediction of the biofilm response. In
      this study, in vitro biofilms of eight clinical Staphylococcus epidermidis
      strains were subjected to treatment with vancomycin, teicoplanin, oxacillin,
      rifampicin and gentamicin. In addition, the biofilms were subjected to
      combinations of an antibiotic with rifampicin. The effects on the biofilms were
      assessed by crystal violet staining to determine the total biofilm biomass,
      staining with XTT to determine bacterial cell viability, and microscopy.
      Combining these methods showed that treatment of S. epidermidis biofilms with
      glycopeptides increased the total biofilm biomass and that these antibiotics were
      not effective in killing bacteria embedded in biofilms. The decreased killing
      efficacy was more pronounced in biofilms produced by strains that were classified
      as 'strong' biofilm producers. Rifampicin, oxacillin and gentamicin effectively
      killed biofilm-associated bacteria of all tested strains. Combining antibiotics
      with rifampicin increased the killing efficacy without influencing the total
      biofilm biomass. When vancomycin or teicoplanin were combined with rifampicin,
      the increase in biofilm biomass was neutralised and also the killing efficacy was
      influenced in a positive way. We conclude that the combined methodology used in
      this study showed that glycopeptides were not effective in eradicating S.
      epidermidis biofilms but that combination with rifampicin improved the killing
      efficacy in vitro. 

PMID- 25614359
TI  - Perinatal high-fat diet increases hippocampal vulnerability to the adverse
      effects of subsequent high-fat feeding.
AB  - Epidemiological observations report an increase in fat consumption associated
      with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in
      women of childbearing age. However, the impact of these maternal feeding habits
      on cognitive function in the offspring is unknown. This study aims to investigate
      the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3
      PUFAs ratio on hippocampal function in adult rats. Furthermore, we explored the
      effects of perinatal HFD combined with exposure to HFD after weaning. Dams were
      fed a control diet (C, 12% of energy from lipids, n-6/n-3 PUFAs ratio: 5) or HFD
      (HF, 39% of energy from lipids, n-6/n-3 PUFAs ratio: 39) throughout gestation and
      lactation. At weaning, offspring were placed either on control (C-C, HF-C) or
      high-fat (HF-HF) diets. In adulthood, hippocampus-dependent memory was assessed
      using the water-maze task and potential hippocampal alterations were determined
      by studying PUFA levels, gene expression, neurogenesis and astrocyte morphology.
      Perinatal HFD induced long-lasting metabolic alterations and some changes in gene
      expression in the hippocampus, but had no effect on memory. In contrast, spatial
      memory was impaired in animals exposed to HFD during the perinatal period and
      maintained on this diet. HF-HF rats also exhibited low n-3 and high n-6 PUFA
      levels, decreased neurogenesis and downregulated expression of several plasticity
      related genes in the hippocampus. To determine the contribution of the perinatal
      diet to the memory deficits reported in HF-HF animals, an additional experiment
      was conducted in which rats were only exposed to HFD starting at weaning (C-HF).
      Interestingly, memory performance in this group was similar to controls. Overall,
      our results suggest that perinatal exposure to HFD with an unbalanced n-6/n-3
      ratio sensitizes the offspring to the adverse effects of subsequent high-fat
      intake on hippocampal function. 

PMID- 25614360
TI  - Activation of GPR30 attenuates chronic pain-related anxiety in ovariectomized
      mice.
AB  - Estrogen regulates neuroendocrine and inflammatory processes that play critical
      roles in neuroinflammation, anxiety, and chronic pain. Patients suffering from
      chronic pain often complain of anxiety. However, limited information is available
      regarding the neural circuitry of chronic pain-related anxiety and the related
      function of estrogen. Hindpaw injection of complete Freund's adjuvant (CFA) and
      chronic constriction injury (CCI) of the sciatic nerve induced notable pain
      sensitization and anxiety-like behavior in ovariectomized (OVX) mice. We found
      that the level of G-protein-coupled receptor 30 (GPR30), a membrane estrogen
      receptor, was significantly increased in the basolateral amygdala (BLA) of
      ovariectomized (OVX) mice suffering from chronic inflammatory and neuropathic
      pain. Subcutaneous injection or BLA local infusion of the GPR30 agonist G1
      significantly reduced anxiety-like behavior in CFA-injected and CCI-OVX mice;
      however, this treatment did not alter the nociceptive threshold. GPR30 knock down
      by shRNA in the BLA of OVX mice inhibited the anxiolytic effects of GPR30
      activation. G1 administration reversed the upregulation of GluR1 subunit in AMPA
      and NR2A-containing NMDA receptors and the downregulation of GABAA receptors in
      the BLA of CFA-injected and CCI-OVX mice. Electrophysiological recording revealed
      that GPR30 activation could prevent imbalance between excitatory and inhibitory
      transmissions in the BLA synapses of CFA-injected OVX mice. In conclusion, GPR30
      activation induced anxiolytic effects but did not affect the nociceptive
      threshold of mice under chronic pain. The anxiolytic effects of GPR30 were
      partially due to maintaining the balance between excitatory and inhibitory
      transmissions in the BLA. 

PMID- 25614362
TI  - Revisiting the crystal ball--high content single cells analysis as predictor of
      recovery.

PMID- 25614361
TI  - Ketamine reduces lipopolysaccharide-induced high-mobility group box-1 through
      heme oxygenase-1 and nuclear factor erythroid 2-related factor 2/ p38 mitogen
      activated protein kinase.
AB  - BACKGROUND: Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist,
      is widely used as an intravenous anesthetic agent and has also been shown to
      possess anti-inflammatory effects, but its effects on high-mobility group box-1
      (HMGB1) have not been well defined. In the present study, we investigated the
      effects of ketamine on HMGB1 in lipopolysaccharide (LPS)-induced Raw264.7 cells
      and in a mouse model of cecal ligation and puncture-induced sepsis. MATERIALS AND
      METHODS: Raw264.7 cells were incubated with or without 1 MUg/mL LPS in the
      presence or absence of ketamine, mitogen-activated protein kinases (MAPKs)
      inhibitor, or small interfering RNA (siRNA). The protein and expression levels of
      inflammatory mediators, such as HMGB1, nitric oxide (NO), and heme oxygenase-1
      (HO-1), were measured using enzyme-linked immunosorbent assays, Western blot
      analysis, and real-time polymerase chain reaction. The effect of ketamine on
      nuclear factor erythroid 2-related factor 2 (Nrf2) and MAPKs activation was
      evaluated using enzyme-linked immunosorbent assays and Western blot analysis.
      RESULTS: In vitro, ketamine inhibits HMGB1 and NO release and induces HO-1
      expression in a concentration-dependent manner, whereas HO-1 siRNA antagonizes
      the inhibition of HMGB1 and NO. The effect of ketamine is inhibited by the p38
      MAPK inhibitor SB203580 and Nrf2 siRNA, indicating that ketamine induces HO-1 via
      p38 MAPK and Nrf2. In vivo, ketamine increases survival and decreases serum and
      lung HMGB1 levels in cecal ligation and puncture-induced sepsis. CONCLUSIONS:
      Ketamine inhibits LPS-induced HMGB1 release through HO-1 induction, and these
      effects may be mediated by blockade of p38 MAPK and Nrf2 signaling pathways.

PMID- 25614363
TI  - Semiautomated analysis of embryoscope images: Using localized variance of image
      intensity to detect embryo developmental stages.
AB  - Embryo selection in in vitro fertilization (IVF) treatment has traditionally been
      done manually using microscopy at intermittent time points during embryo
      development. Novel technique has made it possible to monitor embryos using time
      lapse for long periods of time and together with the reduced cost of data
      storage, this has opened the door to long-term time-lapse monitoring, and large
      amounts of image material is now routinely gathered. However, the analysis is
      still to a large extent performed manually, and images are mostly used as
      qualitative reference. To make full use of the increased amount of microscopic
      image material, (semi)automated computer-aided tools are needed. An additional
      benefit of automation is the establishment of standardization tools for embryo
      selection and transfer, making decisions more transparent and less subjective.
      Another is the possibility to gather and analyze data in a high-throughput
      manner, gathering data from multiple clinics and increasing our knowledge of
      early human embryo development. In this study, the extraction of data to
      automatically select and track spatio-temporal events and features from sets of
      embryo images has been achieved using localized variance based on the
      distribution of image grey scale levels. A retrospective cohort study was
      performed using time-lapse imaging data derived from 39 human embryos from seven
      couples, covering the time from fertilization up to 6.3 days. The profile of
      localized variance has been used to characterize syngamy, mitotic division and
      stages of cleavage, compaction, and blastocoel formation. Prior to analysis,
      focal plane and embryo location were automatically detected, limiting
      precomputational user interaction to a calibration step and usable for automatic
      detection of region of interest (ROI) regardless of the method of analysis. The
      results were validated against the opinion of clinical experts. (c) 2015
      International Society for Advancement of Cytometry. 

PMID- 25614368
TI  - Organocatalytic enantioselective decarboxylative reaction of malonic acid half
      thioesters with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl
      cinchona alkaloid amides.
AB  - The organocatalytic enantioselective decarboxylative Mannich reaction of malonic
      acid half thioesters (MAHTs) with cyclic N-sulfonyl ketimines by using N
      heteroarenesulfonyl cinchona alkaloid amides afforded products with high
      enantioselectivity. Both enantiomers of the products could be obtained by using
      pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic
      addition of the MAHTs to the ketimines prior to decarboxylation. 

PMID- 25614369
TI  - A tailor-made specific anion-binding motif in the side chain transforms a
      tetrapeptide into an efficient vector for gene delivery.
AB  - Arginine-rich cell-penetrating peptides are widely utilized as vectors for gene
      delivery. However, their transfection efficacy still needs to be optimized. To
      accomplish this, guanidinocarbonylpyrrole groups, which are tailor-made anion
      binding sites, were introduced into the side chains of tetralysine to obtain the
      peptide analogue 1. In contrast to the common strategy of adding a lipophilic
      tail to peptide vectors, this novel method most likely enhances transfection
      efficacy through more specific interactions between the binding motifs and DNA or
      the cell membrane. Tetrapeptide analogue 1 is thus the smallest peptidic
      transfection vector that has been reported to date. The transfection efficacy of
      1, which on average has less than two positive charges under physiological
      conditions, is even better than that of polyethylenimine (PEI). Furthermore, 1
      exhibits only negligible cytotoxicity, which makes it an interesting candidate
      for further development. 

PMID- 25614370
TI  - Surgical treatment of a case of adult epiglottic laryngomalacia.
AB  - INTRODUCTION: Adult laryngomalacia is rare. It may be idiopathic or secondary to
      trauma or degenerative disease. CASE REPORT: A 25-year-old man presented with
      inspiratory dyspnea on effort of several months' evolution. Flexible endoscopy
      found epiglottic laryngomalacia, managed by CO2 laser V-shaped partial
      epiglottectomy. DISCUSSION: Excessive resection of the epiglottis may lead to
      false passage; insufficient resection risks being ineffective. V-shaped partial
      epiglottectomy minimizes risk of false passage while ensuring permanent
      respiratory airflow via the epiglottic V during epiglottic movement.

PMID- 25614371
TI  - Introduction of an update system for vaccine strains of veterinary influenza
      vaccines in Japan.
AB  - The basic countermeasures used to control highly pathogenic avian influenza
      (HPAI) are early detection procedures and the culling of affected chickens.
      However, if successive HPAI outbreaks occur, the vaccination may be an option for
      controlling HPAI. Therefore, avian influenza (AI) vaccines are stocked by the
      Japanese government. By contrast, equine influenza (EI) vaccine is an effective
      tool for preventing or controlling EI. Because antigenic drifts affect the
      efficacy of AI and EI vaccines, the vaccine strains should be updated rapidly.
      However, the development and registration of veterinary vaccines usually takes
      several years. In response to this issue, the Ministry of Agriculture, Forestry,
      and Fisheries (MAFF) established a system that allows AI and EI vaccine strains
      to be updated rapidly. National Veterinary Assay Laboratory, MAFF, established a
      vaccine strains selection committee for veterinary influenza vaccine. The main
      agendas involve determining whether the current vaccine strains need to be
      updated and selecting the most appropriate vaccine strains. The committee
      concluded that A/duck/Hokkaido/Vac-3/2007(H5N1) was added to the strains of
      stockpiled AI vaccines and that the EI vaccine strains did not need to be
      changed, but that the clade 2 viruses of the Florida sub-lineage strain,
      A/equine/Yokohama/aq13/2010(H3N8) was added to the EI vaccine strain. 

PMID- 25614372
TI  - The importance of formulation in the successful lyophilization of influenza
      reference materials.
AB  - Lyophilized Influenza antigen reference reagents are a critical resource in the
      quality control of influenza vaccines. A standard formulation has been used
      successfully at NIBSC for many years however, following the unexpected occurrence
      of a collapsed appearance in a particular batch a study was carried out to
      establish the impact of the sugar concentration in the formulation using
      modulated differential scanning calorimetry (mDSC) and nuclear magnetic resonance
      spectroscopy (NMR). There was a correlation between the presence and size of the
      mDSC eutectic temperature events and the freeze dried appearance of the cakes,
      which became progressively worse with increasing amounts of sugar. NMR
      spectroscopy could be used to positively identify and quantify the sugars in the
      formulations. MDSC can rapidly predict if the freeze dried appearance will be
      acceptable so as to assure the successful lyophilization of influenza reference
      preparations.

PMID- 25614373
TI  - Using plant traits to predict the sensitivity of colonizations and extirpations
      to landscape context.
AB  - Theory suggests that species with different traits will respond differently to
      landscape fragmentation. Studies have shown that the presence of species in
      fragments of varying size, shape and connectivity is dependent on plant traits
      related to dispersal ability, persistence and disturbance tolerance. However, the
      role of traits in determining long-term plant community changes in response to
      changing landscape context is not well understood. We used data from resurveys of
      184 plots to test the ability of nine plant traits to predict colonizations and
      extirpations between 1968 and 2009 based on the surrounding landscape context. We
      related apparent colonizations and extirpations to road density, naturally
      vegetated area and patch shape and then tested for significant relationships
      between a tendency for positive or negative associations and plant traits.
      Exotic, herbaceous, annual, shade-intolerant species and species with higher
      specific leaf area were more likely than others to colonize plots with higher
      road density, lower amount of naturally vegetated area and higher edge-to-area
      ratio. However, extirpations were rarely predictable based on traits. The role of
      landscape context in structuring plant community change over the past four
      decades in the 184 plots resurveyed was largely mediated by colonization events,
      suggesting that trait-based extirpations occur with a longer post-fragmentation
      time lag or, alternatively, that extirpation is more stochastic with respect to
      plant traits than is colonization. 

PMID- 25614374
TI  - [Comparison of British and French expatriate doctors' characteristics and
      motivations].
AB  - BACKGROUND: Migration of medical practitioners is rarely studied despite its
      importance in medical demography: the objective of this study was to analyze the
      characteristics and motivations of the French doctors settled in the United
      Kingdom and of the British doctors settled in France. METHODS: This cross
      sectional study was conducted using a self-completed questionnaire sent to all
      French doctors practicing in the United Kingdom (in 2005) and all British
      medicine doctors practicing in France (in 2009). The doctors were identified with
      official data from the National Medical Councils: 244 French doctors practicing
      in the United Kingdom and 86 British doctors practicing in France. The
      questionnaire was specifically developed to determine the reasons of moving to
      the other country, and the level of satisfaction after expatriation. RESULTS: A
      total of 98 French doctors (out of 244) and 40 British doctors (out of 86)
      returned the questionnaire. Respondents were mainly general practitioners with a
      professional experience of 8 to 9 years. The sex ratio was near 1 for both groups
      with a majority of women among physicians under 50 years. The motivations were
      different between groups: French doctors were attracted by the conditions offered
      at the National Health Service, whereas British doctors were more interested in
      opportunities for career advancement, joining husband or wife, or favourable
      environmental conditions. Overall, the respondents considered expatriation as
      satisfactory: 84% of French doctors, compared with only 58% of British doctors,
      were satisfied with their new professional situation. CONCLUSION: This study, the
      first in its kind, leads to a clearer understanding of the migration of doctors
      between France and the United Kingdom.

PMID- 25614375
TI  - Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic
      Project on Lung Cancer.
AB  - The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project
      is to identify molecular variables that improve the prognostic and predictive
      accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC).
      Clinical data and lung tissue, tumor and blood samples will be collected from 3
      patient cohorts created for this purpose. The prognostic protein signature will
      be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1
      y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell
      markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13
      genes in the tissue samples will be determined, and inflammatory markers in
      peripheral blood will also be analyzed. Variables that improve the prognostic and
      predictive accuracy of TNM in NSCLC by molecular staging may be identified from
      this extensive analytical panel.

PMID- 25614376
TI  - Pathogenic mechanisms in chronic obstructive pulmonary disease due to biomass
      smoke exposure.
AB  - Chronic obstructive pulmonary disease (COPD) mortality and morbidity have
      increased significantly worldwide in recent decades. Although cigarette smoke is
      still considered the main risk factor for the development of the disease,
      estimates suggest that between 25% and 33% of COPD patients are non-smokers.
      Among the factors that may increase the risk of developing COPD, biomass smoke
      has been proposed as one of the most important, affecting especially women and
      children in developing countries. Despite the epidemiological evidence linking
      exposure to biomass smoke with adverse health effects, the specific cellular and
      molecular mechanisms by which this pollutant can be harmful for the respiratory
      and cardiovascular systems remain unclear. In this article we review the main
      pathogenic mechanisms proposed to date that make biomass smoke one of the major
      risk factors for COPD. 

PMID- 25614377
TI  - Spanish consensus on the prevention and treatment of Pseudomonas aeruginosa
      bronchial infections in cystic fibrosis patients.
AB  - Pseudomonas aeruginosa is the main pathogen in bronchopulmonary infections in
      cystic fibrosis (CF) patients. It can only be eradicated at early infection
      stages while reduction of its bacterial load is the therapeutic goal during
      chronic infection or exacerbations. Neonatal screening and
      pharmacokinetic/pharmacodynamic knowledge has modified the management of CF
      patients. A culture based microbiological follow-up should be performed in
      patients with no infection with P.aeruginosa. At initial infection, inhaled
      colistin (0,5-2MU/tid), tobramycin (300mg/bid) or aztreonam (75mg/tid) with or
      without oral ciprofloxacin (15-20mg/kg/bid, 2-3weeks) are recommended. In chronic
      infections, treatment is based on continuous administration of colistin or with a
      28-day on-off regimen with tobramycin or aztreonam. During mild-moderate
      exacerbations oral ciprofloxacin (2-3weeks) can be administered while serious
      exacerbations must be treated with intravenous combination therapy (beta-lactam
      with an aminoglycoside or a fluoroquinolone). Future studies will support
      antibiotic rotation and/or new combination therapies. Epidemiological measures
      are also recommended to avoid new P.aeruginosa infections and "patient-to-patient
      transmission" of this pathogen. 

PMID- 25614378
TI  - Pleural effusion secondary to actinomyces infection as a late complication of
      laparoscopic cholecystectomy.

PMID- 25614379
TI  - Conservative Approach in Bronchial Artery Aneurysm Rupture: A Therapeutic Option.

PMID- 25614380
TI  - A case of bronchial atresia.

PMID- 25614382
TI  - Hypoxia combined with spheroid culture improves cartilage specific function in
      chondrocytes.
AB  - Controlling the chondrocyte phenotype and function in a physiologically relevant
      microenvironment remains a major challenge for cartilage repair in tissue
      engineering applications. This work presents a straightforward strategy to create
      a high throughput concave microwell array used for generating multicellular
      spheroids of chondrocytes and facilitating the maintenance of the articular
      chondrocyte phenotype and function by combining 3D spheroid culture with hypoxia.
      The polydimethylsiloxane (PDMS) concave microwells were simply produced from a
      concave SU-8 template fabricated using a soft-lithography approach and easily
      adopted for size-controlled spheroid culture. 3D spheroid culture was observed to
      facilitate the cartilage-specific phenotype and function maintenance as compared
      to 2D monolayer culture. Combining hypoxia with spheroid culture markedly
      increased the expressions of cartilage-specific collagen II and aggrecan at
      protein and mRNA levels. The hypoxia-inducible factor (HIF) signaling pathway was
      found to get involved in phenotype maintenance, metabolism and differentiation of
      chondrocytes by regulating HIF-1alpha and HIF-2alpha, respectively. The
      established approach provides a useful platform for a wide range of applications
      in the field of cartilage biology, stem cell research and high throughput 3D drug
      testing in cancer. 

PMID- 25614381
TI  - Deconvolution analysis for classifying gastric adenocarcinoma patients based on
      differential scanning calorimetry serum thermograms.
AB  - Recently, differential scanning calorimetry (DSC) has been acknowledged as a
      novel tool for diagnosing and monitoring several diseases. This highly sensitive
      technique has been traditionally used to study thermally induced protein
      folding/unfolding transitions. In previous research papers, DSC profiles from
      blood samples of patients were analyzed and they exhibited marked differences in
      the thermal denaturation profile. Thus, we investigated the use of this novel
      technology in blood serum samples from 25 healthy subjects and 30 patients with
      gastric adenocarcinoma (GAC) at different stages of tumor development with a new
      multiparametric approach. The analysis of the calorimetric profiles of blood
      serum from GAC patients allowed us to discriminate three stages of cancer
      development (I to III) from those of healthy individuals. After a multiparametric
      analysis, a classification of blood serum DSC parameters from patients with GAC
      is proposed. Certain parameters exhibited significant differences (P < 0.05) and
      allowed the discrimination of healthy subjects/patients from patients at
      different tumor stages. The results of this work validate DSC as a novel
      technique for GAC patient classification and staging, and offer new graphical
      tools and value ranges for the acquired parameters in order to discriminate
      healthy from diseased subjects with increased disease burden. 

PMID- 25614384
TI  - The detection of epileptic seizure signals based on fuzzy entropy.
AB  - BACKGROUND: Entropy is a nonlinear index that can reflect the degree of chaos
      within a system. It is often used to analyze epileptic electroencephalograms
      (EEG) to detect whether there is an epileptic attack. Much research into the
      state inspection of epileptic seizures has been conducted based on sample entropy
      (SampEn). However, the study of epileptic seizures based on fuzzy entropy
      (FuzzyEn) has lagged behind. NEW METHODS: We propose a method of state inspection
      of epileptic seizures based on FuzzyEn. The method first calculates the FuzzyEn
      of EEG signals from different epileptic states, and then feature selection is
      conducted to obtain classification features. Finally, we use the acquired
      classification features and a grid optimization method to train support vector
      machines (SVM). RESULTS: The results of two open-EEG datasets in epileptics show
      that there are major differences between seizure attacks and non-seizure attacks,
      such that FuzzyEn can be used to detect epilepsy, and our method obtains better
      classification performance (accuracy, sensitivity and specificity of
      classification of the CHB-MIT are 98.31%, 98.27% and 98.36%, and of the Bonn are
      100%, 100%, 100%, respectively). COMPARISONS WITH EXISTING METHOD(S): To verify
      the performance of the proposed method, a comparison of the classification
      performance for epileptic seizures using FuzzyEn and SampEn is conducted. Our
      method obtains better classification performance, which is superior to the SampEn
      based methods currently in use. CONCLUSIONS: The results indicate that FuzzyEn is
      a better index for detecting epileptic seizures effectively. The FuzzyEn-based
      method is preferable, exhibiting potential desirable applications for medical
      treatment.

PMID- 25614383
TI  - Simultaneous glutamate recordings in the frontal cortex network with multisite
      biomorphic microelectrodes: New tools for ADHD research.
AB  - BACKGROUND: The aberrant regulation of glutamate has been implicated in numerous
      psychiatric disorders including drug addiction and attention
      deficit/hyperactivity disorder. To understand glutamate signaling and its role in
      facilitating disease, tools to directly measure glutamate in a complex, neural
      network are needed. NEW METHOD: The development of a ceramic-based, dual-sided,
      biomorphic microelectrode array with four recording sites on each side to
      facilitate a more detailed measurement of glutamate in awake, behaving rodents.
      RESULTS: In vitro calibrations of these biosensors showed selective and specific
      responses to glutamate. In awake rats, these biomorphic electrode arrays enabled
      the concurrent evaluation of glutamate in a network, the frontal cortex:
      including the cingulate, prelimbic, infralimbic and dorsal peduncle regions.
      Regions within the frontal cortex exhibited varying phasic glutamate patterns in
      awake animals.Comparison with existing method: Existing methodologies to measure
      glutamate neurotransmission employ single-sided biosensors or biosensors capable
      of measuring neurochemicals at only one location in space. CONCLUSIONS: Multi
      site, biomorphic neurochemical biosensors provide a method for simultaneously
      measuring glutamate in multiple areas of a neural network in the brain.

PMID- 25614385
TI  - Experimental evaluation and computational modeling of tissue damage from low-flow
      push-pull perfusion sampling in vivo.
AB  - BACKGROUND: Neurochemical monitoring via sampling probes is valuable for
      deciphering neurotransmission in vivo. Microdialysis is commonly used; however,
      the spatial resolution is poor. NEW METHOD: Recently push-pull perfusion at low
      flow rates (50nL/min) has been proposed as a method for in vivo sampling from the
      central nervous system. Tissue damage from such probes has not been investigated
      in detail. In this work, we evaluated acute tissue response to low-flow push-pull
      perfusion by infusing the nuclear stains Sytox Orange and Hoechst 33342 through
      probes implanted in the striatum for 200min, to label damaged and total cells,
      respectively, in situ. RESULTS: Using the damaged/total labeled cell ratio as a
      measure of tissue damage, we found that 33+/-8% were damaged within the dye
      region around a microdialysis probe. We found that low-flow push-pull perfusion
      probes damaged 24+/-4% of cells in the sampling area. Flow had no effect on the
      number of damaged cells for low-flow push-pull perfusion. Modeling revealed that
      shear stress and pressure gradients generated by the flow were lower than
      thresholds expected to cause damage. Comparison with existing methods.Push-pull
      perfusion caused less tissue damage but yielded 1500-fold better spatial
      resolution. CONCLUSIONS: Push-pull perfusion at low flow rates is a viable method
      for sampling from the brain with potential for high temporal and spatial
      resolution. Tissue damage is mostly caused by probe insertion. Smaller probes may
      yield even lower damage.

PMID- 25614386
TI  - AnyWave: a cross-platform and modular software for visualizing and processing
      electrophysiological signals.
AB  - BACKGROUND: The importance of digital signal processing in clinical
      neurophysiology is growing steadily, involving clinical researchers and
      methodologists. There is a need for crossing the gap between these communities by
      providing efficient delivery of newly designed algorithms to end users. We have
      developed such a tool which both visualizes and processes data and, additionally,
      acts as a software development platform. NEW METHOD: AnyWave was designed to run
      on all common operating systems. It provides access to a variety of data formats
      and it employs high fidelity visualization techniques. It also allows using
      external tools as plug-ins, which can be developed in languages including C++,
      MATLAB and Python. RESULTS: In the current version, plug-ins allow computation of
      connectivity graphs (non-linear correlation h2) and time-frequency representation
      (Morlet wavelets). The software is freely available under the LGPL3 license.
      COMPARISON WITH EXISTING METHODS: AnyWave is designed as an open, highly
      extensible solution, with an architecture that permits rapid delivery of new
      techniques to end users. CONCLUSIONS: We have developed AnyWave software as an
      efficient neurophysiological data visualizer able to integrate state of the art
      techniques. AnyWave offers an interface well suited to the needs of clinical
      research and an architecture designed for integrating new tools. We expect this
      software to strengthen the collaboration between clinical neurophysiologists and
      researchers in biomedical engineering and signal processing.

PMID- 25614387
TI  - Heart failure with preserved ejection fraction in women: the Dutch Queen of
      Hearts program.
AB  - Heart failure (HF) poses a heavy burden on patients, their families and society.
      The syndrome of HF comes in two types: with reduced ejection fraction (HFrEF) and
      preserved ejection fraction (HFpEF). The latter is on the increase and
      predominantly present in women, especially the older ones. There is an urgent
      need for mortality-reducing drugs in HFpEF, a disease affecting around 5 % of
      those aged 65 years and over. HFpEF develops in patients with risk factors and
      comorbidities such as obesity, hypertension, diabetes, COPD, but also
      preeclampsia. These conditions are likely to drive microvascular disease with
      involvement of the coronary microvasculature, which may eventually evolve into
      HFpEF. Currently, the diagnosis of HFPEF relies mainly on echocardiography. There
      are no biomarkers that can help diagnose female microvascular disease or
      facilitate the diagnosis of (early stages of) HFpEF. Recently a Dutch consortium
      was initiated, Queen of Hearts, with support from the Netherlands Heart
      Foundation, with the aim to discover and validate biomarkers for diastolic
      dysfunction and HFpEF in women. These biomarkers come from innovative blood
      derived sources such as extracellular vesicles and circulating cells. Within the
      Queen of Hearts consortium, we will pursue female biomarkers that have the
      potential for further evolution in assays with point of care capabilities. As a
      spin-off, the consortium will gain knowledge on gender-specific pathology of
      HFpEF, possibly opening up novel treatment options. 

PMID- 25614388
TI  - The complexity, challenges and benefits of comparing two transporter
      classification systems in TCDB and Pfam.
AB  - Transport systems comprise roughly 10% of all proteins in a cell, playing
      critical roles in many processes. Improving and expanding their classification is
      an important goal that can affect studies ranging from comparative genomics to
      potential drug target searches. It is not surprising that different
      classification systems for transport proteins have arisen, be it within a
      specialized database, focused on this functional class of proteins, or as part of
      a broader classification system for all proteins. Two such databases are the
      Transporter Classification Database (TCDB) and the Protein family (Pfam)
      database. As part of a long-term endeavor to improve consistency between the two
      classification systems, we have compared transporter annotations in the two
      databases to understand the rationale for differences and to improve both
      systems. Differences sometimes reflect the fact that one database has a
      particular transporter family while the other does not. Differing family
      definitions and hierarchical organizations were reconciled, resulting in
      recognition of 69 Pfam 'Domains of Unknown Function', which proved to be
      transport protein families to be renamed using TCDB annotations. Of over 400
      potential new Pfam families identified from TCDB, 10% have already been added to
      Pfam, and TCDB has created 60 new entries based on Pfam data. This work, for the
      first time, reveals the benefits of comprehensive database comparisons and
      explains the differences between Pfam and TCDB. 

PMID- 25614389
TI  - Histopathological effects of preoperative chemoradiotherapy for pancreatic
      cancer: an analysis for the impact of radiation and gemcitabine doses.
AB  - BACKGROUND AND PURPOSE: Histopathological findings of patients who underwent
      resection for pancreatic adenocarcinoma (PC) after preoperative chemoradiotherapy
      (CRT) reportedly showed beneficial effects. The purpose of our study was to
      evaluate the correlation between histopathological effects (HE) of preoperative
      CRT and treatment parameters [radiation and gemcitabine (GEM) doses]. MATERIAL
      AND METHODS: HE of CRT were assessed on 158 primary lesions of 157 patients with
      PC who underwent pancreatic resection after preoperative CRT with GEM between
      January 2006 and December 2011. The radiation dose delivered to the primary tumor
      site and surrounding regional nodal areas was 50 Gy until September 2009 followed
      by the dose escalation of a 10 Gy boost added for delivery with the field-in
      field technique to the roots of the celiac and superior mesenteric arteries.
      Intravenous administration of GEM (1000 /m(2)) was initiated concurrently on days
      1, 8, and 15, every 4 weeks and generally repeated for 3 cycles. HE of CRT on the
      primary tumor were categorized based on the number of tumor cells destroyed.
      RESULTS: The median overall survival time was 74.5 months and 3-year and 5-year
      survival rates were 64.3% and 54.5%, respectively. Dose-volume parameters of
      radiation such as D33 with a cut-off value of 51.6 Gy were correlated
      significantly with HE (p=.0230). Lesions having received GEM>7625 mg/m(2) before
      surgical resection more frequently showed positive HE (p=.0002). Multivariate
      logistic regression analysis demonstrated that both D33 and cumulative GEM dose
      were significant predictors of definite HE (p=.0110 and <.0001, respectively).
      CONCLUSIONS: Our retrospective analysis showed that dose intensity of radiation
      and GEM is significantly related to HE of preoperative CRT for PC.

PMID- 25614390
TI  - Induction of intermembrane adhesion by incorporation of synthetic adhesive
      molecules into cell membranes.
AB  - Modulation of cell adhesion by synthetic materials is useful for a wide range of
      biomedical applications. Here, we characterized cell adhesion mediated by a
      semisynthetic molecule, cholesteryl-modified gelatin (chol-gelatin). We found
      that this hybrid molecule facilitated cell adhesion by connecting two apposed
      membranes via multiple cholesterol moieties on the gelatin molecules, whereas
      unmodified gelatin did not bind to cell membranes. Analyses revealed that the
      rate of the formation of cell adhesions was increased by displaying more
      cholesterol moieties on the cell membrane. In contrast, the area of the cell
      adhesion site was unchanged by increasing the number of cholesterol molecules,
      suggesting that chol-gelatin may suppress cell spreading. Such restriction was
      not observed in cell adhesion mediated by the mutant of physiological adhesion
      protein CD2, which lacked its cytoplasmic domain and was unable to connect to
      cytoplasmic actin filaments, but had a similar affinity for its ligand compared
      with the chol-gelatin-cell membrane interaction. Further analysis suggested the
      restriction of cell spreading by chol-gelatin was largely independent of the
      modulation of the surface force, and thus we hypothesize that the restriction
      could be in part due to the modulation of cell membrane mechanics by membrane
      incorporated chol-gelatin. Our study dissected the two roles of the hybrid
      molecule in cell adhesion, namely the formation of a molecular connection and the
      restriction of spreading, and may be useful for designing other novel synthetic
      agents to modulate various types of cell adhesions. 

PMID- 25614391
TI  - Dynamic contrast-enhanced ultrasound for quantification of tissue perfusion.
AB  - Dynamic contrast-enhanced ultrasound (US) imaging, a technique that uses
      microbubble contrast agents with diagnostic US, has recently been technically
      summarized and reviewed by a European Federation of Societies for Ultrasound in
      Medicine and Biology position paper. However, the practical applications of this
      imaging technique were not included. This article reviews and discusses the
      published literature on the clinical use of dynamic contrast-enhanced US. This
      review finds that dynamic contrast-enhanced US imaging is the most sensitive
      cross-sectional real-time method for measuring the perfusion of parenchymatous
      organs noninvasively. It can measure parenchymal perfusion and therefore can
      differentiate between benign and malignant tumors. The most important routine
      clinical role of dynamic contrast-enhanced US is the prediction of tumor
      responses to chemotherapy within a very short time, shorter than using Response
      Evaluation Criteria in Solid Tumors criteria. Other applications found include
      quantifying the hepatic transit time, diabetic kidneys, transplant grafts, and
      Crohn disease. In addition, the problems involved in using dynamic contrast
      enhanced US are discussed. 

PMID- 25614392
TI  - Sonographic markers of fetal alpha-thalassemia major.
AB  - alpha-Thalassemia prevails in Southeast Asia, where alpha-thalassemia major is a
      lethal type. Sonography is a helpful and cost-effective screening tool for
      detecting alpha-thalassemia major fetuses. The cardiothoracic ratio, placental
      thickness, and middle cerebral artery peak systolic velocity are most used in
      clinical practice. These sensitive markers are helpful for evaluation of the
      hemodynamic status and cardiovascular function of the affected fetuses. They can
      predict fetal alpha-thalassemia major and assess the efficacy of treatment
      noninvasively; therefore, the medical costs as well as the possibility of fetal
      loss caused by invasive procedures can be reduced. Other potentially useful
      sonographic markers need further studies, although previous preliminary research
      suggests their usefulness. This article will review those sonographic markers. 

PMID- 25614393
TI  - Usefulness of diagnostic indices comprising clinical, sonographic, and biomarker
      data for discriminating benign from malignant ovarian masses.
AB  - The objective of this study was to review the accuracy of indices combining
      several diagnostic variables, in comparison to other models, sonography alone,
      and biomarker assays, for predicting benign or malignant ovarian lesions.
      Different single modalities were reviewed. The most useful complex models were
      International Ovarian Tumor Analysis (IOTA) sonographic logistic regression model
      2 (area under the curve, 0.949), risk of malignancy index-cancer antigen 125
      human epididymis protein 4 (0.950), risk of malignancy algorithm (0.953), pelvic
      mass score (0.960), non-IOTA logistic regression model (0.970), and histoscanning
      score logistic regression model (0.970). None of the indices was superior to an
      expert subjective sonographic assessment (0.968). For women with adnexal tumors,
      indices with high accuracy are available that are applicable in clinical practice
      and comparable to an expert subjective sonographic assessment for discriminating
      benign from malignant masses. 

PMID- 25614394
TI  - A 2-week elective experience provides comparable training as longitudinal
      exposure during residency for pelvic sonography.
AB  - OBJECTIVES: The purpose of this study was to compare the accuracy of first
      trimester pelvic sonography done by physicians after a 2-week emergency
      ultrasound elective to similarly numbered examinations done by physicians
      longitudinally over several years of residency training. METHODS: We conducted a
      secondary analysis of a previously reported prospective study of pelvic
      sonography for symptomatic first-trimester pregnancy. The 21st through 40th
      examinations were compared between those who completed an emergency ultrasound
      elective and those who did not. The reference standard was pelvic sonography done
      by the department of radiology. RESULTS: Eighty-six examinations (34%) were done
      by 12 operators who did not participate in an emergency ultrasound elective, and
      171 examinations (67%) were done by 13 operators who completed an emergency
      ultrasound elective. There was no statistical difference between the groups with
      regard to identifying an intrauterine pregnancy, molar pregnancy, ectopic
      pregnancy, or adnexal mass. CONCLUSIONS: The accuracy of pelvic sonography for
      first-trimester pregnancy was comparable between physicians who participated in a
      2-week emergency ultrasound elective and those who performed the same number of
      examinations over a longer period during residency training.

PMID- 25614395
TI  - Classification of breast tumors using sonographic texture analysis.
AB  - OBJECTIVES: The purpose of this study was to evaluate a computer-aided diagnostic
      system with texture analysis to improve radiologists' accuracy in identification
      of breast tumors as malignant or benign. METHODS: The database included 20 benign
      and 12 malignant tumors. We extracted 300 statistical texture features as
      descriptors for each selected region of interest in 3 normalization schemes
      (default, MU - 3sigma, and MU + 3sigma, where MU and sigma were the mean value
      and standard deviation, respectively, of the gray-level intensity and 1%-99%).
      Then features determined by the Fisher coefficient and the lowest probability of
      classification error + average correlation coefficient yielded the 10 best and
      most effective features. We analyzed these features under 2 standardization
      states (standard and nonstandard). For texture analysis of the breast tumors, we
      applied principle component, linear discriminant, and nonlinear discriminant
      analyses. First-nearest neighbor classification was performed for the features
      resulting from the principle component and linear discriminant analyses.
      Nonlinear discriminant analysis features were classified by an artificial neural
      network. Receiver operating characteristic curve analysis was used for examining
      the performance of the texture analysis methods. RESULTS: Standard feature
      parameters extracted by the Fisher coefficient under the default and 3sigma
      normalization schemes via nonlinear discriminant analysis showed high performance
      for discrimination between benign and malignant tumors, with sensitivity of
      94.28%, specificity of 100%, accuracy of 97.80%, and an area under the receiver
      operating characteristic curve of 0.9714. CONCLUSIONS: Texture analysis is a
      reliable method and has the potential to be used effectively for classification
      of benign and malignant tumors on breast sonography.

PMID- 25614396
TI  - Spleen size in cirrhosis of different etiologies.
AB  - OBJECTIVES: The purpose of this study was to evaluate the impact of cirrhosis
      etiology on spleen size as measured by sonography and computed tomography (CT).
      METHODS: The spleen images of 139 patients with cirrhosis secondary to alcohol
      abuse, hepatitis C, or nonalcoholic steatohepatitis were reviewed
      retrospectively. The maximum diagonal spleen length on a single sonogram and
      maximum spleen diameter on axial, coronal, or sagittal CT, whichever was largest,
      was compared among the etiologic groups. RESULTS: In 127 patients who underwent
      sonography, the mean spleen size +/- SD on sonography in the alcohol group (13.1
      +/- 2.5 cm) was significantly smaller than in the hepatitis C (15.0 +/- 3.4 cm)
      and nonalcoholic steatohepatitis (15.2 +/- 3.0 cm) groups (95% confidence
      intervals of the mean difference, 0.6 to 3.3 and 0.8 to 3.4 cm, respectively). In
      87 patients who underwent CT, the mean spleen size on CT in the alcohol group
      (14.0 +/- 2.7 cm) was smaller than in the hepatitis C (15.9 +/- 3.4 cm) and
      nonalcoholic steatohepatitis (15.5 +/- 3.6 cm) groups, but the difference was not
      statistically significant. The spleen sizes on both sonography and CT in 79
      patients were strongly correlated (r = 0.88; P < .0001). CONCLUSIONS: Spleen size
      in patients with cirrhosis varies by the etiology of the disease. Therefore, to
      apply spleen size as a diagnostic or prognostic criterion in this context, it is
      important to recognize that cutoff values derived from spleen size in one
      etiologic group may not produce the same results when extrapolated to another
      etiologic group.

PMID- 25614397
TI  - Sonographic inferior vena cava measurements to assess hydration status in college
      football players during preseason camp.
AB  - OBJECTIVES: The purpose of this study was to determine whether sonographic
      measurement of the inferior vena cava (IVC) in college football players during
      preseason camp is a reliable way to detect and monitor dehydration. Our primary
      hypothesis was that IVC diameter measurements, the postpractice caval index, and
      expiratory diameter were significantly related to percent weight loss after a
      preseason football practice. METHODS: A prospective cohort sample of Division I
      intercollegiate football players in preseason training camp was recruited before
      practice. All football players on the active roster who were at least 18 years of
      age were eligible to participate in the study. Sonographic IVC measurements were
      obtained in the long axis using either the subcostal or subxiphoid approach
      during inspiration and expiration both before and after an approximately 3-hour
      practice with moderate to high levels of exertion at high ambient temperatures.
      Player weights were recorded in the locker room before and after practice.
      RESULTS: A total of 27 prepractice and postpractice sonographic measurements were
      obtained. The postpractice expiratory IVC diameter was significantly related to
      percent weight loss after practice (R(2) = 0.153; P = .042), with the IVC
      diameter being significantly inversely correlated with percent weight loss; the
      regression coefficient was -1.07 (95% confidence interval, -2.09 to -0.04). There
      was no statistically significant relationship between percent weight loss and the
      postpractice caval index; the regression coefficient was 0.245 (95% confidence
      interval, -0.10 to 0.59; R(2) = 0.078; P = .16). CONCLUSIONS: The postpractice
      expiratory IVC diameter was significantly related to percent weight loss after
      practice, whereas the caval index was not found to correlate with weight loss.

PMID- 25614398
TI  - Quantitative analysis of right ventricular (RV) function with echocardiography in
      chronic heart failure with no or mild RV dysfunction: comparison with cardiac
      magnetic resonance imaging.
AB  - OBJECTIVES: Right ventricular (RV) performance parameters (tricuspid annular
      plane systolic excursion, systolic longitudinal velocity on tissue Doppler
      imaging, fractional area change, and tissue and 2-dimensional [2D] strain on the
      right free wall) have been validated. In comparative studies, they have been
      correlated with the prognosis of patients with heart failure on radionuclide
      ventriculography and thermodilution in right heart catheterization. This study
      aimed to evaluate RV systolic function in patients with heart failure with no or
      mild RV dysfunction and correlate the above-mentioned echocardiographic
      parameters with the magnetic resonance imaging (MRI)-calculated RV ejection
      fraction (RVEF), stroke volume, end-diastolic volume, and end-systolic volume.
      METHODS: Standard and pulsed Doppler tissue echocardiography and MRI were
      performed in 31 patients with New York Heart Association functional class II and
      III chronic heart failure. RESULTS: A high correlation between tricuspid annular
      plane systolic excursion, systolic longitudinal velocity, tissue strain, and 2D
      strain was noted, whereas the fractional area change did not correlate with any
      other parameter. The RVEF correlated with tricuspid annular plane systolic
      excursion, systolic longitudinal velocity, and tissue and 2D strain (all P< .01);
      under linear regression analysis, the 4 parameters independently correlated with
      RVEF. CONCLUSIONS: Echocardiographic RV performance parameters (tricuspid annular
      plane systolic excursion, systolic longitudinal velocity, tissue strain, and 2D
      strain) correlated with the MRI-calculated RVEF and overall predicted it. In
      particular, RV 2D strain and tissue strain were good markers for RV longitudinal
      motions. These echocardiographic parameters are easily obtained and may give
      important information about RV function for evaluation and prognostic
      stratification of patients with heart failure.

PMID- 25614399
TI  - Volumetric blood flow in transjugular intrahepatic portosystemic shunt revision
      using 3-dimensional Doppler sonography.
AB  - OBJECTIVES: Three-dimensional (3D)/4-dimensional (4D) sonographic measurement of
      blood volume flow in transjugular intrahepatic porto systemic shunt revision with
      the intention of objective assessment of shunt patency. METHODS: A total of 17
      patients were recruited (12 male and 5 female; mean age, 55 years; range, 30-69
      years). An ultrasound system equipped with a 2.0-5.0-MHz probe was used to
      acquire multivolume 3D/4D color Doppler data sets to assess prerevision and
      postrevision shunt volume flow. Volume flow was computed offline based on the
      principle of surface integration of Doppler-measured velocity vectors in a
      lateral-elevational c-surface positioned at the color flow focal depth (range,
      8.0-11.5 cm). Volume flow was compared to routine measurements of the prerevision
      and postrevision portosystemic pressure gradient. Prerevision volume flow was
      compared with the outcome to determine whether a flow threshold for revision
      could be defined. RESULTS: Linear regression of data from revised transjugular
      intrahepatic portosystemic shunt cases showed an inverse correlation between the
      mean-normalized change in prerevision and postrevision shunt volume flow and the
      mean-normalized change in the prerevision and postrevision portosystemic pressure
      gradient (r(2) = 0.51; P = .020). Increased shunt blood flow corresponded to a
      decreased pressure gradient. Comparison of prerevision flows showed preliminary
      threshold development at 1534 mL/min, below which a shunt revision may be
      recommended (P = .21; area under the receiver operating characteristic curve =
      0.78). CONCLUSIONS: Shunt volume flow measurement with 3D/4D Doppler sonography
      provides a potential alternative to standard pulsed wave Doppler metrics as an
      indicator of shunt function and predictor of revision.

PMID- 25614400
TI  - Transcranial color-coded duplex sonography of the middle cerebral artery: more
      than just the M1 segment.
AB  - OBJECTIVES: Routine sonography of the middle cerebral artery in acute ischemic
      stroke usually focuses on the main stem (M1 segment). However, stenoses and
      occlusions affect not only proximal but also more distal vessel branches, such as
      the M2 segments. Transcranial color-coded duplex sonography allows visualization
      of these segments; however, a formal analysis and description of normal blood
      flow values are missing. The purpose of this study was to analyze middle cerebral
      artery branching patterns with transcranial color-coded duplex sonography and to
      establish reference flow velocity values in the detectable M2 branches as well as
      the early temporal M1 branch. METHODS: Transcranial color-coded duplex sonography
      in the axial and coronal planes was performed in 50 participants without vascular
      disease and with a good temporal bone window (ie, fully visible M1 middle
      cerebral artery segment and A1 anterior cerebral artery segment). We analyzed the
      course and branching pattern of the M1 segment, including anatomic variants such
      as an early temporal M1 branch, and measured the length and flow parameters of
      the detectable M2 branches. RESULTS: Assessment of 100 hemispheres allowed
      classification into 3 anatomic patterns: M1 bifurcation (63%), M1 trifurcation
      (32%), and medial M1 branching into 2 major segments (2%). A clear distinction
      was not possible in 3 cases (3%). An early temporal M1 branch was detected in the
      coronal plane in 26%. CONCLUSIONS: Transcranial color-coded duplex sonography is
      a useful tool for analyzing anatomic variants and branching patterns of the
      middle cerebral artery as well as flow characteristics of M2 segments. Therefore,
      it also has potential to increase the diagnostic yield for the detection of
      middle cerebral artery disease in these vessel segments.

PMID- 25614401
TI  - Antivascular ultrasound therapy: magnetic resonance imaging validation and
      activation of the immune response in murine melanoma.
AB  - OBJECTIVES: The purpose of this study was to investigate the treatment effects of
      antivascular ultrasound (US) with dynamic contrast-enhanced magnetic resonance
      imaging (MRI), contrast-enhanced sonography, and histopathologic analysis in a
      murine melanoma model. METHODS: Subcutaneous K1735 murine melanoma tumors were
      grown in syngeneic C3H/HeN mice. Quantitative tumor perfusion characteristics
      were measured before antivascular US treatment with both dynamic contrast
      enhanced MRI and high-resolution contrast-enhanced sonography. Tumors were
      subsequently treated with 1 or 3 minutes of continuous low-intensity US after
      intravenous administration of a US contrast agent. Treatment effects were
      assessed by quantitative dynamic contrast-enhanced MRI, contrast-enhanced
      sonography, histopathologic analysis, and immunohistochemistry. RESULTS: Low
      intensity antivascular US treatment resulted in approximately a doubling and
      tripling of the time to peak enhancement on dynamic contrast-enhanced MRI in the
      1- and 3-minute treatment groups, respectively, along with a significant decrease
      in contrast wash-out (P < .01). There was a potent reduction in tumor perfusion
      on contrast-enhanced sonography, with approximately 40% and 70% reductions in the
      tumor area perfused as assessed by contrast-enhanced sonography after 1 (P < .05)
      and 3 (P < .01) minutes of antivascular US. The pathologic and histologic changes
      spatially correlated with the regions of diminished perfusion seen on contrast
      enhanced sonography and dynamic contrast-enhanced MRI. Antivascular US therapy
      resulted in a significant increase in the number of hypoxia-inducible factor
      1A(+) cells, indicating tumor hypoxia (P < .01), and of CD45(+)/CD3(+) cells in
      tumors after treatment, in keeping with increased T-cell infiltration (P < .01).
      CONCLUSIONS: Antivascular US treatment effects extend beyond direct cytotoxicity
      from hemorrhagic necrosis to include ischemia-mediated cytotoxicity, enhanced
      small molecule retention, and intratumoral immune activation.

PMID- 25614403
TI  - Can renal sonography be a reliable diagnostic tool in the assessment of chronic
      kidney disease?
AB  - OBJECTIVES: Kidney size has been found to be correlated with anthropometric
      features and kidney function. Therefore, we postulate that if the conventionally
      measured renal sonographic parameters (pole-to-pole length, width, and
      parenchymal thickness) are taken according to standardized rules and corrected
      for body height, their association with kidney function could be strengthened,
      thus helping validate renal sonographic information for a better assessment of
      chronic kidney disease (CKD) status. METHODS: This cross-sectional study included
      72 stable adult patients with stage 1 to 4 CKD. Sonographic parameters were
      obtained from both kidneys and averaged, and the measurements obtained were
      further corrected for patients' body height. The glomerular filtration rate (GFR)
      was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation.
      RESULTS: Parenchymal thickness and renal length showed the highest correlation
      level with the GFR. This significant correlation, however, was greatly
      ameliorated by the correction for patients' body height (r = 0.537; P < .001; r =
      0.510; P < .001, respectively). Of note, the product of these two parameters
      corrected for body height showed the best degree of correlation with the GFR (r =
      0.560; P < .001), as confirmed by analysis of variance after subdivision of the
      population into CKD stage groups according to the GFR. Receiver operating
      characteristic curve analysis for discrimination of a GFR of less than 60 mL/min
      indentified the combined parameter as the one with the highest area under the
      curve (0.78; 95% confidence interval, 0.66-0.89), followed renal length corrected
      for height (area under the curve, 0.77; 95% confidence interval, 0.66-0.88).
      CONCLUSIONS: Correction of renal sonographic parameters for body height
      strengthens the degree of the correlation of renal sonography with the GFR. The
      improved correlation with the GFR makes renal sonography a reliable tool for a
      more complete assessment of patients with CKD.

PMID- 25614402
TI  - Anesthetic techniques influence the induction of pulmonary capillary hemorrhage
      during diagnostic ultrasound scanning in rats.
AB  - OBJECTIVES: Pulmonary capillary hemorrhage can be induced by diagnostic
      ultrasound (US) during direct pulmonary US scanning in rats. The influence of
      specific anesthetic techniques on this bioeffect was examined. METHODS: Ketamine
      plus xylazine has been used previously. In this study, the influence of
      intraperitoneal injections of ketamine and pentobarbital, inhalational
      isoflurane, and the supplemental use of xylazine with ketamine and isoflurane was
      tested. A diagnostic US machine with a 7.6-MHz linear array was used to image the
      right lung of anesthetized rats in a warmed water bath at different mechanical
      index (MI) settings. Pulmonary capillary hemorrhage was assessed by measuring
      comet tail artifacts in the image and by morphometry of the hemorrhagic areas on
      excised lungs. RESULTS: Pulmonary capillary hemorrhage was greatest for
      pentobarbital, lower for inhalational isoflurane, and lowest for ketamine
      anesthesia, with occurrence thresholds at MIs of about 0.44, 0.8, and 0.8,
      respectively. Addition of xylazine produced a substantial increase in hemorrhage
      and a significant proportion of hemorrhage occurrence for ketamine at an MI of
      0.7 (P < .01) and for isoflurane at an MI of 0.52 (P < .01). CONCLUSIONS:
      Ketamine plus xylazine and pentobarbital yield lower thresholds than ketamine or
      isoflurane alone by nearly a factor of 2 in MI. These results suggest that the
      choice of the anesthetic agent substantially modifies the relative risks of
      pulmonary capillary hemorrhage from pulmonary US.

PMID- 25614404
TI  - Thyroid malignancy markers on sonography are common in patients with benign
      thyroid disease and previous iodine deficiency.
AB  - OBJECTIVES: The purpose of this study was to evaluate the characteristics of
      benign thyroid nodules on sonography and ultrasound elastography in a population
      exposed to iodine deficiency. METHODS: We conducted a prospective systematic
      evaluation of preoperative thyroid sonography and elastography in patients
      assigned for surgical excision of benign thyroid nodules. Two experienced
      sonographers performed all sonographic and elastographic examinations. Thyroid
      nodules were evaluated by 7 generally accepted sonographic malignancy risk
      markers and assigned an elasticity score on elastography. The final diagnosis of
      a benign thyroid nodule was based on histopathologic analysis of resected thyroid
      gland tissue. RESULTS: We evaluated 232 thyroid nodules in 105 patients (86 women
      and 19 men). In total, 57% of the examined nodules had 1 or 2 malignancy risk
      markers present, and 24% did not have any markers present. A solid nodule larger
      than 15 mm was the most common malignancy risk marker observed (63%), followed by
      low elasticity (33%), microcalcifications (26%), and hypoechogenicity (15%). In
      an analysis stratified according to the number of nodules (solitary versus
      multiple), low elasticity was described more frequently in solitary nodules
      (61.9% versus 30.4%; P= .004). A large nodular volume was a predictor (P < .05)
      of microcalcifications and intranodular vascularization, whereas an absent halo
      sign and a solid nodule were found less frequently in nodules with larger
      volumes. CONCLUSIONS: Our results show that routine preoperative malignancy risk
      evaluation of presumably benign thyroid nodules is of little value when performed
      on patients exposed to iodine deficiency.

PMID- 25614405
TI  - Primary thyroid lymphoma has different sonographic and color Doppler features
      compared to nodular goiter.
AB  - OBJECTIVES: The purpose of this study was to determine the specific sonographic
      features of primary thyroid lymphoma and its color Doppler pattern compared to
      nodular goiter. METHODS: The sonographic findings for 13 surgically proven
      primary thyroid lymphomas were analyzed and compared to those for 27 nodular
      goiters. RESULTS: In accordance with the suggested pathologic patterns, the
      sonographic patterns of primary thyroid lymphoma could be classified into diffuse
      and nodular or segmental types based on the distribution of hypoechoic and
      echogenic structures within the lesions. Some common sonographic characteristics
      suggesting thyroid malignancy could not facilitate differentiation of primary
      thyroid lymphoma from nodular goiter. However, a central blood flow pattern would
      favor the diagnosis of primary thyroid lymphoma, whereas a peripheral pattern
      would suggest the diagnosis of nodular goiter. CONCLUSIONS: Primary thyroid
      lymphoma has characteristic sonographic and Doppler flow features. Along with
      several other parameters, a central blood flow pattern would highly suggest the
      diagnosis of primary thyroid lymphoma rather than nodular goiter.

PMID- 25614406
TI  - Sonographically guided sternoclavicular joint injection: description of technique
      and validation.
AB  - OBJECTIVES: The primary purpose of this investigation was to describe and
      validate a sonographically guided technique for injecting the sternoclavicular
      joint (SCJ) using a cadaveric model. METHODS: A single experienced operator
      (J.S.) completed 13 sonographically guided SCJ injections on 7 unembalmed
      cadaveric specimens (4 male and 3 female) using an out-of-plane, caudad-to
      cephalad technique to place 1 mL of diluted blue latex into the joint. Within 72
      hours, study coinvestigators dissected each specimen to determine the injectate
      location. RESULTS: All 13 injections accurately placed latex into the SCJ with a
      predilection for the clavicular side (accuracy, 100%; 95% confidence interval,
      73%-100%). Three injections (23%) placed all latex on the clavicular side of the
      SCJ in the presence of a complete intra-articular disk. Dissection revealed
      incomplete degenerated disks in the remaining 10 joints. Seven of these
      injections (54%) clearly placed more than 80% of the latex on the clavicular
      side, whereas the remaining 3 injections (23%) showed nearly equal latex
      distribution between the clavicular and sternal sides. No injection resulted in
      neurovascular injury or extracapsular flow. CONCLUSIONS: Sonographically guided
      SCJ injections can be considered in the diagnosis and management of patients
      presenting with medial shoulder pain syndromes and, using the technique described
      herein, have a predilection to target the clavicular portion of the joint. In
      younger patients with possible complete intra-articular disks or in patients with
      sternal-side conditions, practitioners should consider confirming sternal-side
      flow after injection or attempt to specifically target the sternal side of the
      joint.

PMID- 25614407
TI  - Comparative effectiveness of infraclavicular and supraclavicular perineural
      catheters for ultrasound-guided through-the-catheter bolus anesthesia.
AB  - OBJECTIVES: Using a through-the-needle local anesthetic bolus technique,
      ultrasound-guided infraclavicular perineural catheters have been shown to provide
      greater analgesia compared to supraclavicular catheters. A through-the-catheter
      bolus technique, which arguably "tests" the anesthetic efficacy of the catheter
      before initiating an infusion, has been validated for infraclavicular catheters
      but not supraclavicular catheters. This study investigated the through-the
      catheter bolus technique for supraclavicular catheters and tested the hypothesis
      that infraclavicular catheters provide faster onset of brachial plexus
      anesthesia. METHODS: Preoperatively, patients were randomly assigned to receive
      either a supraclavicular or an infraclavicular catheter using an ultrasound
      guided nonstimulating catheter insertion technique with a mepivacaine bolus via
      the catheter and ropivacaine perineural infusion initiated postoperatively. The
      primary outcome was time to achieve complete sensory anesthesia in the ulnar and
      median nerve distributions. Secondary outcomes included procedural time,
      procedure-related pain and complications, and postoperative pain, opioid
      consumption, sleep disturbances, and motor weakness. RESULTS: Fifty patients were
      enrolled in the study; all but 2 perineural catheters were successfully placed
      per protocol. Twenty-one of 24 (88%) and 24 of 24 (100%) patients in the
      supraclavicular and infraclavicular groups, respectively, achieved complete
      sensory anesthesia by 30 minutes (P= .088). There was no difference in the time
      to achieve complete sensory anesthesia. Supraclavicular patients reported more
      sleep disturbances postoperatively, but there were no statistically significant
      differences in other outcomes. CONCLUSIONS: Both supraclavicular and
      infraclavicular perineural catheters using a through-the-catheter bolus technique
      provide effective brachial plexus anesthesia.

PMID- 25614408
TI  - Utility of compact ultrasound in a mass surgical selection program in Africa:
      experience of a sonologist at the MV Africa Mercy Hospital Ship's screening day.
AB  - Compact ultrasound (US) was introduced in an austere setting with no other
      available imaging for an annual mass surgical screening day. Compact US
      examinations were performed on 25 patients from more than 7000 potential
      patients, as deemed possibly useful by the screening surgeons. Of the 20 patients
      with recorded data, compact US was helpful in 14 of 20 as a decision-making tool,
      obviating computed tomography for preoperative planning. Compact US was helpful
      in most cases, saving resources (computed tomography), technologist time, and
      radiation risk in this select population. 

PMID- 25614409
TI  - Postnatal diagnosis of 22q11.2 deletion syndrome in fetal megalourethra.

PMID- 25614410
TI  - Reversal of mirror syndrome after selective feticide of a hydropic fetus in a
      dichorionic diamniotic twin pregnancy.

PMID- 25614411
TI  - A case of 45,X/47,XYY mosaicism in a male fetus with a hypoplastic nasal bone.

PMID- 25614412
TI  - Turner syndrome presenting with echogenic fetal lungs on first-trimester
      sonography.

PMID- 25614413
TI  - Functional roles of the hexamer organization of plant glutamate decarboxylase.
AB  - Glutamate decarboxylase (GAD) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme
      that catalyzes the alpha-decarboxylation of glutamate to gamma-aminobutyrate. A
      unique feature of plant GAD is the presence of a calmodulin (CaM)-binding domain
      at its C-terminus. In plants, transient elevation of cytosolic Ca2+ in response
      to different types of stress is responsible for GAD activation via CaM. The
      crystal structure of GAD isoform 1 from Arabidopsis thaliana (AtGAD1) shows that
      the enzyme is a hexamer composed of a trimer of dimers. Herein, we show that in
      solution AtGAD1 is in a dimer-hexamer equilibrium and estimate the dissociation
      constant (Kd) for the hexamer under different conditions. The association of
      dimers into hexamers is promoted by several conditions, including high protein
      concentrations and low pH. Notably, binding of Ca2+/CaM1 abolishes the
      dissociation of the AtGAD1 oligomer. The AtGAD1 N-terminal domain is critical for
      maintaining the oligomeric state as removal of the first 24 N-terminal residues
      dramatically affects oligomerization by producing a dimeric enzyme. The deleted
      mutant retains decarboxylase activity, highlighting the dimeric nature of the
      basic structural unit of AtGAD1. Site-directed mutagenesis identified Arg24 in
      the N-terminal domain as a key residue since its mutation to Ala prevents hexamer
      formation in solution. Both dimeric mutant enzymes form a stable hexamer in the
      presence of Ca2+/CaM1. Our data clearly reveal that the oligomeric state of
      AtGAD1 is highly responsive to a number of experimental parameters and may have
      functional relevance in vivo in the light of the biphasic regulation of AtGAD1
      activity by pH and Ca2+/CaM1 in plant cells. This article is part of a special
      issue titled "Cofactor-Dependent Proteins: Evolution, Chemical Diversity and Bio
      applications."

PMID- 25614414
TI  - Identification of proteins associated with Aha1 in HeLa cells by quantitative
      proteomics.
AB  - The identification of the activator of heat shock protein 90 (Hsp90) ATPase's
      (Aha1) protein-protein interaction (PPI) network will provide critical insights
      into the relationship of Aha1 with multi-molecular complexes and shed light onto
      Aha1's interconnections with Hsp90-regulated biological functions. Flag-tagged
      Aha1 was over-expressed in HeLa cells and isolated by anti-Flag affinity pull
      downs, followed by trypsin digestion and identification co-adsorbing proteins by
      liquid chromatography-tandem mass spectroscopy (LC-MS/MS). A probability-based
      identification of Aha1 PPIs was generated from the LC-MS/MS analysis by using a
      relative quantification strategy, spectral counting (SC). By comparing the SC
      based protein levels between Aha1 pull-down samples and negative controls, 164
      Aha1-interacting proteins were identified that were quantitatively enriched in
      the pull-down samples over the controls. The identified Aha1-interacting proteins
      are involved in a wide number of intracellular bioprocesses, including DNA
      maintenance, chromatin structure, RNA processing, translation, nucleocytoplasmic
      and vesicle transport, among others. The interactions of 33 of the identified
      proteins with Aha1 were further confirmed by Western blotting, demonstrating the
      reliability of our affinity-purification-coupled quantitative SC-MS strategy. Our
      proteomic data suggests that Aha1 may participate in diverse biological pathways
      to facilitate Hsp90 chaperone functions in response to stress. 

PMID- 25614415
TI  - Comparison of neointimal coverage and extra-stent lumen between sirolimus and
      everolimus-eluting stent using optical coherence tomography.
AB  - The external lumen of a stent [defined as extra-stent lumen (ESL)] assessed by
      optical coherence tomography (OCT) may be related to the risk of thrombus
      formation after sirolimus-eluting stent (SES) implantation. An everolimus-eluting
      stent (EES) might provide relatively minimal inflammatory reaction and
      appropriate neointimal coverage. The purpose of this study was to compare the
      neointimal thickness and ESL between SES and EES. Patients who underwent OCT
      examination more than 7 months after either SES or EES implantation were
      enrolled. Stent area (SA), lumen area (LA), neointimal area (NIA) and neointimal
      thickness (NIT) of each strut were measured at 1-mm intervals between stented
      segments. The area, angle (summation per cross-section) and depth (maximum
      distance from adjacent vessel surface to the outline of stent) of ESL were
      analyzed. A total of 49 lesions were included (SES n = 20, EES n = 29). Mean
      follow-up period was 11 months. A total of 998 cross-sections and 9874 struts
      were analyzed. There were no differences in stent area, lumen area and neointimal
      area (SA: 6.01 +/- 1.60 vs. 6.02 +/- 1.40 mm(2), p = 0.572, LA: 5.37 +/- 1.52 vs.
      5.29 +/- 1.34 mm(2), p = 0.692, NIA: 0.64 +/- 0.49 vs. 0.72 +/- 0.37 mm(2), p =
      0.493). Mean NIT of SES and EES were 0.11 +/- 0.05 and 0.10 +/- 0.05 mm,
      respectively (p = 0.367). Conversely, area, angle and depth of ESL in SES group
      were significantly greater than those in EES group (0.20 +/- 0.39 vs. 0.03 +/-
      0.09 mm(2), p < 0.001, 56.2 +/- 59.1 degrees  vs. 20.1 +/- 41.9 degrees , p <
      0.001, 0.10 +/- 0.09 vs. 0.03 +/- 0.03 mm, p < 0.001). OCT showed that the
      efficacy of neointimal growth suppression is similar between SES and EES, whereas
      the adverse vascular response after EES implantation is smaller than that after
      SES implantation.

PMID- 25614416
TI  - Safety of high-dose-rate stereotactic body radiotherapy.
AB  - BACKGROUND AND PURPOSE: Flattening filter free (FFF) beams with high dose rate
      are increasingly used for stereotactic body radiotherapy (SBRT), because they
      substantially shorten beam-on time. The physical properties of these beams
      together with potentially unknown radiobiological effects might affect patient
      safety. Therefore here we analyzed the clinical outcome of our patients. MATERIAL
      AND METHODS: Between 3/2010 and 2/2014 84 patients with 100 lesions (lung 75,
      liver 10, adrenal 6, lymph nodes 5, others 4) were treated with SBRT using 6 MV
      FFF or 10 MV FFF beams at our institution. Clinical efficacy endpoints and
      toxicity were assessed by Kaplan-Meier analysis and CTCAE criteria version 4.0.
      RESULTS: Median follow-up was 11 months (range: 3-41). No severe acute toxicity
      was observed. There has been one case of severe late toxicity (1%), a grade 3
      bile duct stricture that was possibly related to SBRT. For all patients, the 1
      year local control rate, progression free survival and overall survival were 94%,
      38% and 80% respectively, and for patients with lung lesions 94%, 48% and 83%,
      respectively. CONCLUSIONS: No unexpected toxicity occurred. Toxicity and
      treatment efficacy are perfectly in range with studies investigating SBRT with
      flattened beams. The use of FFF beams at maximum dose rate for SBRT is time
      efficient and appears to be safe.

PMID- 25614417
TI  - Complete dissociation and reassembly behavior as studied by using poly(ethylene
      glycol)-block-poly(glutamate sodium) and kanamycin A.
AB  - Kanamycin A, an amino modified sugar, can interact with poly(ethylene glycol)
      block-poly(glutamate sodium) (PEG114-PGlu64) via electrostatic interactions (with
      PGlu) and hydrogen bonding (with PEG). The interplay of these two forces
      determines the assembly process and the resulting structure. In deionized water,
      kanamycin A and PEG114-PGlu64 form a spherical structure at [+]/[-] = 3.5. This
      structure dissociates instantly and completely in the presence of 30 mM NaCl.
      However, a new structure is reassembled in about 2 hours. A similar phenomenon is
      observed when the buffer pH is increased from 7.8 to 8.3. We attribute the
      distinct dissociation/reassembly process to the reestablishment of the balance
      between electrostatic interactions and hydrogen bonding. The
      dissociation/reassembly process in response to environmental changes offers a
      novel approach to release the loaded cargo in a controlled manner. 

PMID- 25614418
TI  - Benefit of anticoagulation unlikely in patients with atrial fibrillation and a
      CHA2DS2-VASc score of 1.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) and >=1 point on the stroke
      risk scheme CHA2DS2-VASc (congestive heart failure, hypertension, age >=75 years,
      diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74
      years, sex category) are considered at increased risk for future stroke, but the
      risk associated with a score of 1 differs markedly between studies. OBJECTIVES:
      The goal of this study was to assess AF-related stroke risk among patients with a
      score of 1 on the CHA2DS2-VASc. METHODS: We conducted this retrospective study of
      140,420 patients with AF in Swedish nationwide health registries on the basis of
      varying definitions of "stroke events." RESULTS: Using a wide "stroke" diagnosis
      (including hospital discharge diagnoses of ischemic stroke as well as unspecified
      stroke, transient ischemic attack, and pulmonary embolism) yielded a 44% higher
      annual risk than if only ischemic strokes were counted. Including stroke events
      in conjunction with the index hospitalization for AF doubled the long-term risk
      beyond the first 4 weeks. For women, annual stroke rates varied between 0.1% and
      0.2% depending on which event definition was used; for men, the corresponding
      rates were 0.5% and 0.7%. CONCLUSIONS: The risk of ischemic stroke in patients
      with AF and a CHA2DS2-VASc score of 1 seems to be lower than previously reported.

PMID- 25614419
TI  - Adding rigor to stroke risk prediction in atrial fibrillation.

PMID- 25614420
TI  - 1-year risk-adjusted mortality and costs of percutaneous coronary intervention in
      the Veterans Health Administration: insights from the VA CART Program.
AB  - BACKGROUND: There is significant interest in measuring health care value, but
      this concept has not been operationalized in specific patient cohorts. The
      longitudinal outcomes and costs for patients after percutaneous coronary
      intervention (PCI) provide an opportunity to measure an aspect of health care
      value. OBJECTIVES: This study evaluated variations in 1-year outcomes (risk
      adjusted mortality) and risk-standardized costs of care for all patients
      undergoing PCI in the Veterans Affairs (VA) system from 2007 to 2010. METHODS:
      This retrospective cohort study evaluated all veterans undergoing PCI at any of
      60 hospitals in the VA health care system, using data from the national VA
      Clinical Assessment, Reporting, and Tracking (CART) program. Primary outcomes
      were 1-year mortality and costs following PCI. Risk-standardized mortality and
      cost ratios were calculated, adjusting for cardiac and noncardiac comorbidities.
      RESULTS: A median of 261 PCIs were performed in the 60 hospitals during the study
      period. Median 1-year unadjusted hospital mortality rate was 6.13%. Four
      hospitals were significantly above the 1-year risk-standardized median mortality
      rate, with median mortality ratios ranging from 1.23 to 1.28. No hospitals were
      significantly below median mortality. Median 1-year total unadjusted hospital
      costs were $46,302 per patient. There were 16 hospitals above and 19 hospitals
      below the risk-standardized median cost, with risk-standardized ratios ranging
      from 0.45 to 2.09, reflecting a much larger magnitude of variability in costs
      than in mortality. CONCLUSIONS: There is much smaller variation in 1-year risk
      adjusted mortality than in risk-standardized costs after PCI in the VA. These
      findings suggest that there are opportunities to improve PCI value by reducing
      costs without compromising outcomes. This approach to evaluating outcomes and
      costs together may be a model for other health systems and accountable care
      organizations interested in operationalizing value measurement.

PMID- 25614421
TI  - Defining value in percutaneous coronary intervention: "the price of everything
      and the value of nothing".

PMID- 25614422
TI  - The risk for type B aortic dissection in Marfan syndrome.
AB  - BACKGROUND: Aortic dissections involving the descending aorta are a major
      clinical problem in patients with Marfan syndrome. OBJECTIVES: The purpose of
      this study was to identify clinical parameters associated with type B aortic
      dissection and to develop a risk model to predict type B aortic dissection in
      patients with Marfan syndrome. METHODS: Patients with the diagnosis of Marfan
      syndrome and magnetic resonance imaging or computed tomographic imaging of the
      aorta were followed for a median of 6 years for the occurrence of type B
      dissection or the combined end point of type B aortic dissection, distal aortic
      surgery, and death. A model using various clinical parameters as well as
      genotyping was developed to predict the risk for type B dissection in patients
      with Marfan syndrome. RESULTS: Between 1998 and 2013, 54 type B aortic
      dissections occurred in 600 patients with Marfan syndrome (mean age 36 +/- 14
      years, 52% male). Independent variables associated with type B aortic dissection
      were prior prophylactic aortic surgery (hazard ratio: 2.1; 95% confidence
      interval: 1.2 to 3.8; p = 0.010) and a proximal descending aorta diameter >=27 mm
      (hazard ratio: 2.2; 95% confidence interval: 1.1 to 4.3; p = 0.020). In the risk
      model, the 10-year occurrence of type B aortic dissection in low-, moderate-, and
      high-risk patients was 6%, 19%, and 34%, respectively. Angiotensin II receptor
      blocker therapy was associated with fewer type B aortic dissections (hazard
      ratio: 0.3; 95% confidence interval: 0.1 to 0.9; p = 0.030). CONCLUSIONS:
      Patients with Marfan syndrome with prior prophylactic aortic surgery are at
      substantial risk for type B aortic dissection, even when the descending aorta is
      only slightly dilated. Angiotensin II receptor blocker therapy may be protective
      in the prevention of type B aortic dissections.

PMID- 25614423
TI  - Distal aorta: the next frontier in managing Marfan syndrome aortic disease.

PMID- 25614424
TI  - Underutilization of high-intensity statin therapy after hospitalization for
      coronary heart disease.
AB  - BACKGROUND: National guidelines recommend use of high-intensity statins after
      hospitalization for coronary heart disease (CHD) events. OBJECTIVES: This study
      sought to estimate the proportion of Medicare beneficiaries filling prescriptions
      for high-intensity statins after hospital discharge for a CHD event and to
      analyze whether statin intensity before hospitalization is associated with statin
      intensity after discharge. METHODS: We conducted a retrospective cohort study
      using a 5% random sample of Medicare beneficiaries between 65 and 74 years old.
      Beneficiaries were included in the analysis if they filled a statin prescription
      after a CHD event (myocardial infarction or coronary revascularization) in 2007,
      2008, or 2009. High-intensity statins included atorvastatin 40 to 80 mg,
      rosuvastatin 20 to 40 mg, and simvastatin 80 mg. RESULTS: Among 8,762 Medicare
      beneficiaries filling a statin prescription after a CHD event, 27% of first post
      discharge fills were for a high-intensity statin. The percent filling a high
      intensity statin post-discharge was 23.1%, 9.4%, and 80.7%, for beneficiaries not
      taking statins pre-hospitalization, taking low/moderate-intensity statins, and
      taking high-intensity statins before their CHD event, respectively. Compared with
      beneficiaries not on statin therapy pre-hospitalization, multivariable adjusted
      risk ratios for filling a high-intensity statin were 4.01 (3.58-4.49) and 0.45
      (0.40-0.52) for participants taking high-intensity and low/moderate-intensity
      statins before their CHD event, respectively. Only 11.5% of beneficiaries whose
      first post-discharge statin fill was for a low/moderate-intensity statin filled a
      high-intensity statin within 365 days of discharge. CONCLUSIONS: The majority of
      Medicare beneficiaries do not fill high-intensity statins after hospitalization
      for CHD.

PMID- 25614425
TI  - Gaps in guideline implementation: a cause for concern, time for action.

PMID- 25614426
TI  - Device-detected atrial fibrillation: what to do with asymptomatic patients?
AB  - Atrial fibrillation (AF) is the most common clinically significant arrhythmia and
      conveys an increased risk of stroke, regardless of whether it is symptomatic.
      Despite multiple studies supporting an association between subclinical atrial
      tachyarrhythmias (ATs) detected by cardiac implantable electronic devices and
      increased risk of thromboembolic events, clinical intervention for device
      detected AT remains sluggish, with some clinicians delaying treatment and instead
      opting for continued surveillance for additional or longer episodes. However, the
      2014 updated clinical practice guidelines on AF recommend use of the CHA2DS2-VASc
      stroke risk score for nonvalvular AF, with oral anticoagulation recommended for
      scores >=2, regardless of whether AF is paroxysmal, persistent, or permanent.
      This paper reviews the epidemiology of AF and mechanisms of stroke in AF, and
      discusses device-detected AF and its clinical implications. 

PMID- 25614427
TI  - Aortic stenosis and perioperative risk with noncardiac surgery.
AB  - Aortic stenosis (AS) is characterized as a high-risk index for cardiac
      complications during noncardiac surgery. The American College of
      Cardiology/American Heart Association guidelines define severe AS as aortic valve
      area <=1 cm(2), mean gradient of >=40 mm Hg, and peak velocity of >=4 m/s. As per
      current clinical practice, any of these characteristic features label a patient
      as at high risk for noncardiac surgery. However, these parameters appear
      inconsistent, particularly with respect to the aortic valve area cutoff value.
      The perioperative risk associated with AS during noncardiac surgery depends upon
      its severity (moderate vs. severe), clinical status, and the complexity of the
      surgical procedure (low to intermediate risk vs. high risk). A critical analysis
      of old and new data from published studies indicates that the significance of the
      presence of AS in patients undergoing noncardiac surgery is overemphasized in
      studies that predate the more recent advances in echocardiography and cardiac
      catheterization in assessment of aortic stenosis, anesthetic and surgical
      techniques, as well as post-operative patient care. 

PMID- 25614428
TI  - Academic versus private cardiology: preparing for a successful career after
      fellowship.

PMID- 25614429
TI  - The effect of rosuvastatin on platelet-leukocyte interactions in the setting of
      acute coronary syndrome.

PMID- 25614430
TI  - Infective endocarditis involving apparently structurally normal valves in
      patients without previously recognized predisposing heart disease.

PMID- 25614431
TI  - Percutaneous access, no matter what!

PMID- 25614432
TI  - Reply: percutaneous access, no matter what!

PMID- 25614433
TI  - Could late enhancement and need for permanent pacemaker implantation in patients
      undergoing TAVR be explained by undiagnosed transthyretin cardiac amyloidosis?

PMID- 25614434
TI  - Reply: could late enhancement and need for permanent pacemaker implantation in
      patients undergoing TAVR be explained by undiagnosed transthyretin cardiac
      amyloidosis?

PMID- 25614435
TI  - Reply: could late enhancement and need for permanent pacemaker implantation in
      patients undergoing TAVR be explained by undiagnosed transthyretin cardiac
      amyloidosis?

PMID- 25614436
TI  - Gene expression pattern of some classes of cytochrome P-450 and glutathione S
      transferase enzymes in differentiated hepatocytes-like cells from menstrual blood
      stem cells.
AB  - Recently, valuable characteristics of menstrual blood stem cells (MenSCs) have
      impelled scientists to take its advantages for cell therapy of different diseases
      including liver disorders. In this study, we examined messenger RNA (mRNA)
      expression levels of phases I and II drug metabolizing enzymes including
      glutathione S-transferase (GST) and cytochrome P-450 (CYP) in differentiated
      hepatocyte-like cells from MenSCs. The isolated MenSCs were characterized and
      differentiated into hepatocyte-like cells using hepatocyte growth factor (HGF)
      and oncostatin M (OSM) in combination with other components in serum-free culture
      media. After primary characterization of hepatocyte markers, mRNA expression of
      GSTA1, GSTA2, GSTP1, CYP3A4, and CYP7A1 was assessed in differentiated cells in
      reference to undifferentiated cells using real-time PCR. Based on
      immunofluorescent staining and real-time PCR data, the differentiated MenSCs
      could express functional hepatocyte markers at mRNA and/or protein levels
      suggesting development of hepatocyte-like cells from MenSCs. Moreover, the
      expression levels of GSTA1, GSTA2, and CYP3A4 mRNA were upregulated in
      differentiated cells compared to undifferentiated cells. The expression of CYP7A1
      gene was also remarkable on the last day of differentiation process. However, the
      expression level of GSTP1 did not exhibit statistically significant change during
      differentiation (P = 0.6). Based on accumulative data, MenSCs could be viewed as
      an accessible population of stem cells with differentiation ability into drug
      metabolizing hepatocyte-like cells.

PMID- 25614437
TI  - Schizophrenia, antipsychotic drugs and cardiovascular risk: Descriptive study in
      primary care.

PMID- 25614438
TI  - Which psychotic experiences are associated with a need for clinical care?
AB  - BACKGROUND: The aims of this study were to identify (1) the factor structure of
      anomalous experiences across the psychosis continuum; (2) qualitative and
      quantitative differences in psychotic experiences (PEs) between "non need-for
      care" and two clinical groups: psychosis patients and individuals at ultra high
      risk (UHR) of psychosis. We aimed to distinguish which types of experiences would
      be related to malign (need-for-care and/or help-seeking) versus benign outcomes.
      METHODS: Component scores obtained from a Principal Components Analysis of PEs
      from lifetime scores on the Appraisals of Anomalous Experience Inventory (Brett
      et al., 2007) were compared across 96 participants: patients diagnosed with a
      psychotic disorder (n=37), help-seeking UHR people (n=21), and non-clinical
      individuals presenting with enduring PEs (n=38). RESULTS: A five-component
      structure provided the best solution, comprising dissociative-type experiences,
      subjective cognitive deficits, and three separate components relating to
      "positive" symptoms. All groups reported "positive" experiences, such as ideas of
      reference and hallucinations, with the non-clinical group displaying more PEs in
      the Paranormal/Hallucinatory component than both clinical groups.
      "Cognitive/Attentional anomalies" was the only component where the clinical
      groups reported significantly more anomalies than the non-clinical group. However
      psychosis patients reported more frequent first-rank type symptoms and
      "hypomanic" type PEs than the other groups. DISCUSSION: "Positive" PEs were
      common across the psychosis spectrum, although first-rank type symptoms were
      particularly marked in participants diagnosed with a psychotic disorder. Help
      seeking and need-for-care were associated with the presence of subjective
      cognitive disturbances. These findings suggest that anomalies of cognition and
      attention may be more relevant to poorer outcomes than the presence of anomalous
      experiences.

PMID- 25614439
TI  - Diagnostic problems of salivary gland tumors.
AB  - Fine needle aspiration cytology (FNAC) of salivary gland is a popular technique
      with high sensitivity and specificity. However, the interpretation of FNAC smear
      of salivary gland lesions is a great challenge to the cytologists. The
      cytological features of the various tumors of the salivary gland have overlapping
      cytological features and many other lesions in the head neck region may mimic
      salivary lesions. Moreover, at times it may be difficult to differentiate benign
      from malignant tumor of the tumor with same cell of origin. In this article, we
      have discussed the various problems in the diagnosis of FNAC of the salivary
      gland lesions.

PMID- 25614440
TI  - Olfactory identification in amnestic and non-amnestic mild cognitive impairment
      and its neuropsychological correlates.
AB  - BACKGROUND: Olfactory identification impairment in amnestic mild cognitive
      impairment (aMCI) patients is well documented and considered to be caused by
      underlying Alzheimer's disease (AD) pathology, contrasting with less clear
      evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of
      olfactory identification dysfunction in aMCI, naMCI, controls and mild AD
      dementia and (b) assess the relation between olfactory identification and
      cognitive performance in aMCI compared to naMCI. METHODS: 75 patients with aMCI
      and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the
      multiple choice olfactory identification Motol Hospital Smell Test with 18
      different odors together with a comprehensive neuropsychological examination.
      RESULTS: Controlling for age and gender, patients with aMCI and naMCI did not
      differ significantly in olfactory identification and both performed significantly
      worse than controls (p<0.001), albeit also better than patients with mild AD
      (p<.001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory
      and visuospatial tests were significantly related to better olfactory
      identification ability. Conversely, no cognitive measure was significantly
      related to olfactory performance in naMCI. CONCLUSION: Olfactory identification
      is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to
      cognitive impairment in aMCI but not in naMCI.

PMID- 25614441
TI  - Executive dysfunction is a strong stroke predictor.
AB  - BACKGROUND: Although stroke is known to result in executive dysfunction, little
      is known about executive dysfunction as a risk factor for stroke. METHODS:
      Canadian Study of Health and Aging (CSHA), a longitudinal population based study
      of elderly Canadians, was conducted in three waves in 1990-1991 (CSHA-1), 1995
      1996 (CSHA-2), and 2001-2002 (CSHA-3). In a cross-sectional analysis on CSHA-1
      subjects, any association between stroke history and cognitive function was
      studied. In a prospective analysis, CSHA-1 stroke-free subjects were followed to
      CSHA-2 to see if there was any difference in stroke incidence among subjects with
      different baseline cognitive status. And, in a validation study CSHA-2 stroke
      free subjects were followed to CSHA-3 to see if the prospective analyses findings
      could be replicated. FINDINGS: In the cross-sectional analysis, subjects who had
      stroke in their history had significantly lower executive function, not memory
      function, scores than subjects without any stroke in their history. In the
      prospective and validation studies, stroke incidence was affected by neither
      executive nor memory scores. When the analysis was restricted to normal cognition
      subjects, lower executive function, not memory function, scores predicted stroke
      incidence, and remained significant after controlling for stroke risk factors.
      CONCLUSION: We found executive dysfunction to be a powerful stroke risk factor
      among cognitively normal subjects. Testing for executive dysfunction may help
      identify individuals at risk for stroke in time to prevent them.

PMID- 25614442
TI  - Evaluation of plaque stability in extracranial carotid atherosclerotic disease:
      Role of vascular inflammation.

PMID- 25614444
TI  - Need for DISCUSS(ion).

PMID- 25614445
TI  - Synthesis of fluorinated and nonfluorinated graphene quantum dots through a new
      top-down strategy for long-time cellular imaging.
AB  - Herein, a new strategy has been developed through combining a microwave-assisted
      technique with hydrothermal treatment to reduce graphene waste and improve
      production yield of graphene quantum dots (GQDs) prepared by top-down methods. By
      using fluorinated graphene oxide (FGO) as a raw material, fluorinated GQDs and
      nonfluorinated GQDs can be synthesized. Additionally, in the fluorinated GQDs,
      the protective shell supplied by fluorine improves the pH stability of
      photoluminescence and the strong electron-withdrawing group, -F, reduces the pi
      electron density of the aromatic structure; thus inhibiting reactivity toward
      singlet oxygen produced during irradiation and improving the photostability.
      Therefore, the as-prepared fluorinated GQDs with excellent photo- and pH
      stability are suitable for long-term cellular imaging.

PMID- 25614443
TI  - Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in
      human cells.
AB  - Telomere extension has been proposed as a means to improve cell culture and
      tissue engineering and to treat disease. However, telomere extension by nonviral,
      nonintegrating methods remains inefficient. Here we report that delivery of
      modified mRNA encoding TERT to human fibroblasts and myoblasts increases
      telomerase activity transiently (24-48 h) and rapidly extends telomeres, after
      which telomeres resume shortening. Three successive transfections over a 4 d
      period extended telomeres up to 0.9 kb in a cell type-specific manner in
      fibroblasts and myoblasts and conferred an additional 28 +/- 1.5 and 3.4 +/- 0.4
      population doublings (PDs), respectively. Proliferative capacity increased in a
      dose-dependent manner. The second and third transfections had less effect on
      proliferative capacity than the first, revealing a refractory period. However,
      the refractory period was transient as a later fourth transfection increased
      fibroblast proliferative capacity by an additional 15.2 +/- 1.1 PDs, similar to
      the first transfection. Overall, these treatments led to an increase in absolute
      cell number of more than 10(12)-fold. Notably, unlike immortalized cells, all
      treated cell populations eventually stopped increasing in number and expressed
      senescence markers to the same extent as untreated cells. This rapid method of
      extending telomeres and increasing cell proliferative capacity without risk of
      insertional mutagenesis should have broad utility in disease modeling, drug
      screening, and regenerative medicine.

PMID- 25614447
TI  - Sequence Variation in Mature MicroRNA-499 Confers Unfavorable Prognosis of Lung
      Cancer Patients Treated with Platinum-Based Chemotherapy.
AB  - PURPOSE: This study was implemented to investigate the associations between SNP
      in mature microRNA (miRNA) sequence and lung cancer prognosis and to verify the
      function of those SNP. EXPERIMENTAL DESIGN: Eight SNPs (rs3746444T>C in hsa-mir
      499, rs4919510C>G in hsa-mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in
      hsa-mir-4293, rs2168518G>A in hsa-mir-4513, rs8078913T>C in hsa-mir-4520a,
      rs11237828T>C in hsa-mir-5579, and rs9295535T>C in hsa-mir-5689) were analyzed in
      a southern Chinese population with 576 patients with lung cancer, and the
      significant results were validated in two additional cohorts of 346 and 368
      patients, respectively. A series of experiments were performed to evaluate the
      relevancies of those potentially functional SNPs. RESULTS: We found that the
      microRNA-499 rs3746444T>C polymorphism exhibited a consistently poor prognosis
      for patients with lung cancer in the discovery set [HR, 1.24; 95% confidence
      interval (CI), 1.02-1.49; P = 0.028], in the validation set I (HR, 1.31; 95% CI,
      1.01-1.71; P = 0.048) and in the validation set II (HR, 1.45; 95% CI, 1.12-1.86;
      P = 0.004). The adverse effect of CT/CC variants was more remarkable in patients
      receiving platinum-based chemotherapy. Further functional assays demonstrated
      that the rs3746444C variant allele influences the expression of several cancer
      related genes and affects lung cancer cells' proliferation and tumor growth in
      vivo and in vitro via the cisplatinum resistance. CONCLUSION: Our findings
      suggested that the rs3746444T>C polymorphism in mature miR-499 sequence could
      contribute to poor prognosis by modulating cancer-related genes' expression and
      thus involve tumorigenesis and anti-chemotherapy, which may be a useful biomarker
      to predict lung cancer patients' prognosis.

PMID- 25614446
TI  - Bevacizumab in Patients with Nonsquamous Non-Small Cell Lung Cancer and
      Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II
      Study.
AB  - PURPOSE: The phase II prospective, noncomparative BRAIN study (NCT00800202)
      investigated efficacy and safety of bevacizumab in chemotherapy-naive or
      pretreated patients with non-small cell lung cancer (NSCLC) and asymptomatic
      untreated brain metastases to provide data in this previously unexplored
      subgroup. EXPERIMENTAL DESIGN: Patients with stage IV nonsquamous NSCLC, Eastern
      Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic
      brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin
      (area under the curve *6) and paclitaxel (200 mg/m(2)) every 3 weeks (B + CP), or
      second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression
      free survival (PFS) was the primary endpoint. The trial could be stopped if there
      were more than three (B + CP) or more than two (B + E) intracranial hemorrhages.
      RESULTS: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a
      median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median
      overall survival (OS) of 16.0 months. Investigator-assessed overall response rate
      (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions.
      Because of low enrolment (n = 24), efficacy results for the second-line B + E
      cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3
      months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse
      events were comparable with previous trials of bevacizumab. One grade 1
      intracranial hemorrhage occurred and resolved without sequelae. CONCLUSIONS: The
      BRAIN study demonstrates encouraging efficacy and acceptable safety of
      bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and
      asymptomatic, untreated brain metastases.

PMID- 25614449
TI  - Bioflavour production from tomato and pepper pomaces by Kluyveromyces marxianus
      and Debaryomyces hansenii.
AB  - Bioflavours are called natural flavour and/or fragrance compounds which are
      produced using metabolic pathway of the microorganism and/or plant cells or their
      enzyme systems with bioengineering approaches. The aim of this study was to
      investigate bioflavour production from tomato and red pepper pomaces by
      Kluyveromyces marxianus and Debaryomyces hansenii. Obtained specific growth rates
      of K. marxianus and D. hansenii in tomato pomace were 0.081/h and 0.177/h,
      respectively. The bioflavour profile differed between the yeasts. Both yeasts can
      produce esters and alcohols such as phenyl ethyl alcohol, isoamyl alcohol,
      isoamyl acetate, phenyl ethyl acetate and isovaleric acid. "Tarhana" and "rose"
      were descriptive flavour terms for tomato and pepper pomaces fermented by K.
      marxianus, respectively. Tomato pomace fermented by D. hansenii had the most
      intense "green bean" flavour while "fermented vegetable" and "storage/yeast" were
      defined as characteristic flavour terms for pepper pomaces fermented by D.
      hansenii.

PMID- 25614450
TI  - Carotene-degrading activities from Bjerkandera adusta possess an application in
      detergent industries.
AB  - Four extracellular enzymes, a versatile peroxidase, a manganese peroxidase, a dye
      decolorizing peroxidase and a lignin peroxidase were discovered in liquid
      cultures of the basidiomycete Bjerkandera adusta. All of them cleaved beta
      carotene effectively. Expression was enhanced in the presence of beta-carotene or
      Coomassie Brilliant Blue and peaked after 7-9 days. The monomeric proteins were
      purified by ion exchange and size exclusion chromatography and exhibited
      molecular masses of 41, 43, 51 and 43 kDa, respectively. The coding sequences
      showed homologies from 61 to 89 % to peroxidases from other basidiomycetes. The
      novel enzymes retained strong activity even in the absence of hydrogen peroxide
      and at alkaline pH. De-staining of fabrics using detergent-tolerant enzymes may
      help to save the most important bio-resources, energy and water, in washing
      processes and led to green processes in textile cleaning.

PMID- 25614448
TI  - Global promoter methylation analysis reveals novel candidate tumor suppressor
      genes in natural killer cell lymphoma.
AB  - PURPOSE: To identify tumor suppressor genes epigenetically silenced by promoter
      hypermethylation in extranodal natural killer cell lymphoma (NKCL). EXPERIMENTAL
      DESIGN: Promoter methylation was analyzed with global and locus-specific
      methylation assays in NKCL cases and NK cell lines. Gene expression profiles were
      used to identify genes for which aberrant promoter methylation was associated
      with transcriptional silencing. Selected DNA methylations were validated by RRBS,
      pyrosequencing, or q-MSP. Decitabine treatment was performed to evaluate
      reactivation of methylated genes. The tumor suppressor effect of silenced genes
      was evaluated functionally by reintroducing them into NK cell lines. RESULTS: We
      observed significant promoter hypermethylation in most NKCL samples compared with
      normal NK cells. Correlation of global promoter methylation with gene expression
      profiles identified 95 genes with strong evidence for being silenced because of
      promoter methylation, including BCL2L11 (BIM), DAPK1, PTPN6 (SHP1), TET2, SOCS6,
      and ASNS. Known tumor suppressor genes were significantly overrepresented in this
      set of genes. Decitabine treatment of NK cell lines was associated with
      reexpression of all 10 selected methylated and silenced genes. Ectopic expression
      of frequently silenced BIM in two BIM-nonexpressing NK cell lines led to
      increased apoptosis and eventual elimination of BIM-transduced cells. It also
      sensitized these cell lines to chemotherapy-induced apoptosis. Similarly,
      reintroduction of SOCS6 significantly inhibited growth in SOCS6-nonexpressing NK
      cell lines. NK cell lines lacking ASNS expression showed increased sensitivity to
      treatment with l-asparaginase. Reintroduction of ASNS reduced drug sensitivity.
      CONCLUSION: Promoter region hypermethylation is frequent in NKCL, and aberrantly
      methylated genes are pathologically and clinically significant.

PMID- 25614451
TI  - Suitability of the isolated chicken eye test for classification of extreme pH
      detergents and cleaning products.
AB  - A.I.S.E. investigated the suitability of the regulatory adopted ICE in vitro test
      method (OECD TG 438) with or without histopathology to identify detergent and
      cleaning formulations having extreme pH that require classification as EU CLP/UN
      GHS Category 1. To this aim, 18 extreme pH detergent and cleaning formulations
      were tested covering both alkaline and acidic extreme pHs. The ICE standard test
      method following OECD Test Guideline 438 showed good concordance with in vivo
      classification (83%) and good and balanced specificity and sensitivity values
      (83%) which are in line with the performances of currently adopted in vitro test
      guidelines, confirming its suitability to identify Category 1 extreme pH
      detergent and cleaning products. In contrast to previous findings obtained with
      non-extreme pH formulations, the use of histopathology did not improve the
      sensitivity of the assay whilst it strongly decreased its specificity for the
      extreme pH formulations. Furthermore, use of non-testing prediction rules for
      classification showed poor concordance values (33% for the extreme pH rule and
      61% for the EU CLP additivity approach) with high rates of over-prediction (100%
      for the extreme pH rule and 50% for the additivity approach), indicating that
      these non-testing prediction rules are not suitable to predict Category 1 hazards
      of extreme pH detergent and cleaning formulations. 

PMID- 25614452
TI  - Positioning trocars for performing sleeve gastrectomy. Points of controversy.

PMID- 25614454
TI  - Perioperative medicine: why do we care?

PMID- 25614453
TI  - A Multiple Regression Analysis of Postoperative Complications After Body
      Contouring Surgery: a Retrospective Analysis of 205 Patients : Regression
      Analysis of Complications.
AB  - BACKGROUND: As bariatric surgery becomes ever more popular, so does body
      contouring surgery to eliminate excess skin after radical weight loss. To date,
      the literature has described a number of risk factors affecting the postoperative
      outcome. Our study aimed to define those factors more closely, focusing on
      abdominoplasty ("tummy tuck") patients who suffered intra- and postoperative
      complications. METHODS: The study collective included 205 patients over 5 years
      (2001-2006) who underwent dermolipectomy at our department. The mean follow-up
      was 5.94 years. Every abdominoplasty was performed under general anesthesia with
      intraoperative one-dose antibiotic. The analysis included a complete review of
      all medical records. Statistical analysis was performed with the R-2.5.0 Software
      for Windows. RESULTS: The overall rate for major complications that required
      operative revision and/or antibiotics was 10.2 %, including 2.9 % cases of
      infections. Forty-one percent had minor complications, such as seromas,
      hematomas, wound healing problems, and wound dehiscences. The logistic regression
      models demonstrated that smoking combined with the age, a BMI higher than 30
      kg/m(2), and the amount of removed tissue (measured in g) lead to significantly
      more wound healing problems in nearly all age groups. The probability of
      infections correlated with later drain removal. CONCLUSIONS: Regardless of the
      amount of tissue removed, no main risk factor for complications could be
      identified. A complication-free course and good outcome can be best achieved with
      careful patient selection and preoperative planning.

PMID- 25614455
TI  - Characterization of the activity of 2'-C-methylcytidine against dengue virus
      replication.
AB  - Dengue virus (DENV) is a severe mosquito-borne viral pathogen. Neither vaccines
      nor antiviral therapy is currently available to treat DENV infection. Nucleoside
      inhibitors targeting viral polymerase have proved promising for the development
      of drugs against viruses. In this study, we report a nucleoside analog, 2'-C
      methylcytidine (2CMC), which exerts potent anti-DENV activity in DENV subgenomic
      RNA replicon and infectious systems, with an IC50 value of 11.2+/-0.3MUM. This
      study utilized both cell-based and cell-free reporter assay systems to reveal the
      specific anti-DENV RNA polymerase activity of 2CMC. In addition, both xenograft
      bioluminescence-based DENV replicon and DENV-infected Institute of Cancer
      Research (ICR) suckling mice models evaluated the anti-DENV replication activity
      of 2CMC in vivo. Collectively, these findings provide a promising compound for
      the development of direct-acting antivirals against DENV infection. 

PMID- 25614456
TI  - Prevalence of the hepatitis C virus NS3 polymorphism Q80K in genotype 1 patients
      in the European region.
AB  - Hepatitis C virus (HCV) NS3 polymorphism Q80K is mainly found in patients with
      HCV genotype (G) 1a, and has been associated with a reduced treatment response to
      simeprevir with pegylated interferon (P) and ribavirin (R). Prevalence of Q80K
      among G1 patients may vary geographically. Q80K prevalence in the North-American
      G1 population in a recent study was 34%. We conducted a post hoc meta-analysis of
      Q80K polymorphism prevalence among HCV G1-infected patients enrolled in
      simeprevir and telaprevir Phase II/III studies. Baseline HCV NS3/4A protease
      sequences were analysed by population sequencing to determine Q80K prevalence.
      Overall, of 3349 patients from 25 countries in the European region analysed,
      35.8%, 63.8% and 0.3% of patients had G1a, G1b and other/unknown HCV G1 subtypes,
      respectively. Q80K was detected at baseline in 7.5% of HCV G1 patients overall.
      Examination by subtype showed that 19.8%, 0.5% and 18.2% of patients with G1a,
      G1b and other/unknown HCV G1 subtypes had the Q80K polymorphism, respectively.
      Among countries in the European region with sequencing data available for either
      ?20 patients with G1a and/or ?40 G1 patients overall, the Q80K prevalence in G1
      ranged from 0% in Bulgaria to 18.2% in the UK. Q80K prevalence also varied within
      G1a across different countries. HCV subtype 1a was correctly determined in 99% of
      patients by the LiPA v2 assay. A low overall prevalence of Q80K was observed in
      HCV G1-infected patients in the European region, compared with North America.
      However, the prevalence varied by country, due to differing ratios of G1a/G1b and
      differing Q80K prevalence within the G1a populations. 

PMID- 25614457
TI  - Aberrant DNA methylation of DLX4 and SIM1 is a predictive marker for disease
      progression of uterine cervical low-grade squamous intraepithelial lesion.
AB  - BACKGROUND: A few uterine cervical low-grade squamous intraepithelial lesions
      (LSILs) are known to progress with high-risk human papillomavirus (hrHPV).
      METHODS: One hundred and thirteen patients were classified into four groups
      according to their cervical cytology, hrHPV infection, and follow up. Cytology
      samples were examined for aberrant DNA methylation of DLX4 and SIM1 genes and
      protein expressions. CaSki cells were treated with 5-Aza-2'-deoxycytidine (5-aza
      dC). RESULTS: Group 1 was negative for intraepithelial lesions or malignancies.
      LSIL in group 2 showed a continuance of LSIL for longer than 365 days and LSIL in
      group 3 showed an upgrading to high-grade (H) SIL or higher (HSIL+) within 365
      days of LSIL diagnosis. Group 4 was squamous cell carcinoma. All but group 1 were
      infected with hrHPV. Significant differences existed in the frequency of DNA
      methylation between groups 2 and 3 (p = 0.044), between groups 3 and 4 (p =
      0.020) for DLX4, and between groups 1 and 3 (p = 0.0003), and groups 2 and 3 (p =
      0.005) for the SIM1 gene. DLX4 protein expression was significantly reduced in
      the DLX4 methylation positive tissues (p = 0.008). The 5-aza-dC treatment
      restored DLX4 mRNA expressions of CaSki cells (p < 0.005). The LSIL cases with
      DNA methylation of the SIM1 gene, or both genes, progressed faster to HSIL+ than
      did the others (p = 0.033 and p = 0.045, respectively). CONCLUSION: Aberrant DNA
      methylation of the DLX4 and SIM1 genes should be a novel progression marker for
      uterine cervical LSIL with hrHPV infection.

PMID- 25614458
TI  - Acetaminophen attenuates glomerulosclerosis in obese Zucker rats via reactive
      oxygen species/p38MAPK signaling pathways.
AB  - Focal segmental glomerulosclerosis is a critical pathological lesion in metabolic
      syndrome-associated kidney disease that, if allowed to proceed unchecked, can
      lead to renal failure. However, the exact mechanisms underlying
      glomerulosclerosis remain unclear, and effective prevention strategies against
      glomerulosclerosis are currently limited. Herein, we demonstrate that chronic low
      dose ingestion of acetaminophen (30 mg/kg/day for 6 months) attenuates
      proteinuria, glomerulosclerosis, podocyte injury, and inflammation in the obese
      Zucker rat model of metabolic syndrome. Moreover, acetaminophen treatment
      attenuated renal fibrosis and the expression of profibrotic factors (fibronectin,
      connective tissue growth factor, transforming growth factor beta), reduced
      inflammatory cell infiltration into the glomeruli, and decreased the expression
      of monocyte chemoattractant protein, glutathione (GSH) reductase, and nuclear
      factor erythroid 2-related factor 2, but increased the level of GSH synthetase in
      obese animals. Further in vivo and in vitro studies using human renal mesangial
      cells exposed to high glucose or hydrogen peroxide suggested that the
      renoprotective effects of acetaminophen are characterized by diminished renal
      oxidative stress and p38MAPK hyperphosphorylation.

PMID- 25614459
TI  - Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as
      useful biomarkers of endotoxin-induced oxidative stress.
AB  - This is the newest report in a series of publications aiming to identify a blood
      based antioxidant biomarker that could serve as an in vivo indicator of oxidative
      stress. The goal of the study was to test whether acutely exposing Gottingen mini
      pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants
      from plasma. We set as a criterion that a significant effect should be measured
      in plasma and seen at both doses and at more than one time point. Animals were
      injected with two doses of LPS at 2.5 and 5 ug/kg iv. Control plasma was
      collected from each animal before the LPS injection. After the LPS injection,
      plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls
      at the same time point, statistically significant losses were not found for
      either dose at multiple time points in any of the following potential markers:
      ascorbic acid, tocopherols (alpha, delta, gamma), ratios of GSH/GSSG and
      cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric
      acid, total GSH, and total Cys were significantly increased, probably because LPS
      had a harmful effect on the liver. The leakage of substances from damaged cells
      into the plasma may have increased plasma antioxidant concentrations, making
      changes difficult to interpret. Although this study used a mini-pig animal model
      of LPS-induced oxidative stress, it confirmed our previous findings in different
      rat models that measurement of antioxidants in plasma is not useful for the
      assessment of oxidative damage in vivo.

PMID- 25614461
TI  - Buthionine sulfoximine, an inhibitor of glutathione biosynthesis, induces
      expression of soluble epoxide hydrolase and markers of cellular hypertrophy in a
      rat cardiomyoblast cell line: roles of the NF-kappaB and MAPK signaling pathways.
AB  - Evidence suggests that upregulation of soluble epoxide hydrolase (sEH) is
      associated with the development of myocardial infarction, dilated cardiomyopathy,
      cardiac hypertrophy, and heart failure. However, the upregulation mechanism is
      still unknown. In this study, we treated H9C2 cells with buthionine sulfoximine
      (BSO) to explore whether oxidative stress upregulates sEH gene expression and to
      identify the molecular and cellular mechanisms behind this upregulatory response.
      Real-time PCR and Western blot analyses were used to measure mRNA and protein
      expression, respectively. We demonstrated that BSO significantly upregulated sEH
      at mRNA levels in a concentration- and time-dependent manner, leading to a
      significant increase in the cellular hypertrophic markers, atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP). Furthermore, BSO significantly
      increased the cytosolic phosphorylated IkappaB-alpha and translocation of NF
      kappaB p50 subunits, as measured by Western blot analysis. This level of
      translocation was paralleled by an increase in the DNA-binding activity of NF
      kappaB P50 subunits. Moreover, our results demonstrated that pretreatment with
      the NF-kappaB inhibitor PDTC significantly inhibited BSO-mediated induction of
      sEH and cellular hypertrophic marker gene expression in a dose-dependent manner.
      Additionally, mitogen-activated protein kinases (MAPKs) were transiently
      phosphorylated by BSO treatment. To understand further the role of MAPKs pathway
      in BSO-mediated induction of sEH mRNA, we examined the role of extracellular
      signal-regulated kinase (ERK), c-JunN-terminal kinase (JNK), and p38 MAPK.
      Indeed, treatment with the MEK/ERK signal transduction inhibitor, PD98059,
      partially blocked the activation of IkappaB-alpha and translocation of NF-kappaB
      p50 subunits induced by BSO. Moreover, pretreatment with MEK/ERK signal
      transduction inhibitors, PD98059 and U0126, significantly inhibited BSO-mediated
      induction of sEH and cellular hypertrophic marker gene expression. These results
      clearly demonstrated that the NF-kappaB signaling pathway is involved in BSO
      mediated induction of sEH gene expression, and appears to be associated with the
      activation of the MAPK pathway. Furthermore, our findings provide a strong link
      between sEH-induced cardiac dysfunction and involvement of NF-kappaB in the
      development of cellular hypertrophy. 

PMID- 25614462
TI  - Histopathology of Disseminated Mycobacterium bovis Infection Complicating
      Intravesical BCG Immunotherapy for Urothelial Carcinoma.
AB  - Intravesical instillation of Bacillus Calmette-Guerin (BCG) is a mainstay of
      adjunctive therapy for superficial bladder cancer. Disseminated BCG infection
      ("BCG-osis") after this therapy is rare and potentially life-threatening; only
      isolated case reports detail the histopathologic findings thereof, few of which
      had a diagnosis confirmed by molecular testing. We report 3 additional cases of
      BCG-osis complicating BCG therapy, all confirmed by cultures and molecular
      assays, including the first cases of wedge biopsy-confirmed BCG pneumonia and BCG
      olecranon bursitis. When suggested by a relevant clinical history, recognition of
      randomly distributed granulomas in any organ should prompt consideration of BCG
      osis and liberal performance of AFB stains, aided by targeted molecular assays.
      Physicians should maintain a high index of suspicion when miliary infiltrates
      arise after intravesical BCG instillation, and close multidisciplinary
      communication is essential. Pathologist awareness of this rare cause of
      granulomatous inflammation aids recognition of BCG-osis and facilitates prompt
      initiation of antimycobacterial therapy. 

PMID- 25614460
TI  - Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA
      repair-dependent gene expression linked to essential biological processes.
AB  - Reactive oxygen species inflict oxidative modifications on various biological
      molecules, including DNA. One of the most abundant DNA base lesions, 8-oxo-7,8
      dihydroguanine (8-oxoG) is repaired by 8-oxoguanine DNA glycosylase-1 (OGG1)
      during DNA base excision repair (OGG1-BER). 8-OxoG accumulation in DNA has been
      associated with various pathological and aging processes, although its role is
      unclear. The lack of OGG1-BER in Ogg1(-/-) mice resulted in decreased
      inflammatory responses and increased susceptibility to infections and metabolic
      disorders. Therefore, we proposed that OGG1 and/or 8-oxoG base may have a role in
      immune and homeostatic processes. To test our hypothesis, we challenged mouse
      lungs with OGG1-BER product 8-oxoG base and changes in gene expression were
      determined by RNA sequencing and data were analyzed by Gene Ontology and
      statistical tools. RNA-Seq analysis identified 1592 differentially expressed (>=
      3-fold change) transcripts. The upregulated mRNAs were related to biological
      processes, including homeostatic, immune-system, macrophage activation,
      regulation of liquid-surface tension, and response to stimulus. These processes
      were mediated by chemokines, cytokines, gonadotropin-releasing hormone receptor,
      integrin, and interleukin signaling pathways. Taken together, these findings
      point to a new paradigm showing that OGG1-BER plays a role in various biological
      processes that may benefit the host, but when in excess could be implicated in
      disease and/or aging processes. 

PMID- 25614463
TI  - Periductal Stromal Sarcoma of the Breast With Liposarcomatous Differentiation: A
      Case Report With 10-Year Follow-up and Literature Review.
AB  - A biphasic tumor with features of benign ductal elements and a malignant stromal
      component that lacks the architecture of a phylloides tumor represents a
      diagnostic challenge. A 35-year-old woman presented with a painful mass located
      in the upper inner quadrant of the right breast. A biopsy revealed histologically
      that the tumor had a multinodular architecture with malignant spindle cells
      forming cuffs around multiple open benign ducts. No leaf-like architecture was
      present. In addition, liposarcomatous differentiation was seen in focal areas.
      Immunohistochemical staining showed positive for CD34, vimentin and CDK4, and
      negative for ER, PR, Her2/neu, CD10, CD117, p63, bcl-2, cytokeratin, and MDM2. A
      diagnosis of periductal stromal sarcoma with liposarcomatous differentiation was
      established. Following excision with mastectomy and adjuvant chemotherapy, the
      patient was disease-free for 10 years. To our knowledge, this is the first case
      report of periductal stromal sarcoma showing liposarcomatous differentiation. 

PMID- 25614465
TI  - Corrigendum.
AB  - Su TF, Chao TK, Lee HS, Perng CL, Nieh S. Malignant potential of endometrial
      stromal tumor with limited infiltration: a case report. Int J Surg Pathol.
      2014;22:559-563. Original doi: 10.1177/1066896913506934. The institute name
      "(1)National Defense Medical Center, Taipei, Taiwan" on page 559 was incomplete.
      The correct affiliation of the authors is 1TRI-SERVICE GENERAL HOSPITAL: ,
      National Defense Medical Center, Taipei, Taiwan. 

PMID- 25614464
TI  - Clinical and histopathological diagnosis of glomus tumor: an institutional
      experience of 138 cases.
AB  - BACKGROUND: Glomus tumors are relatively uncommon subcentimeteric benign
      perivascular neoplasms usually located on the fingers. With their blue-red color
      and common subungual location, they are commonly confused for vascular or
      melanocytic lesions. To date there is no comprehensive review of an institutional
      experience with glomus tumors. METHODS: A 14-year retrospective review of all
      cases within University of California, Los Angeles, with either a clinical or
      pathological diagnosis of glomus tumor was performed. Data obtained included
      demographic information, tumor description, pathological diagnoses,
      immunohistochemical studies, radiographic and treatment information, and clinical
      course. Rates of concordance between clinical and pathological diagnoses and an
      evaluation of overlap with other entities were assessed. RESULTS: Clinical
      diagnosis of glomus tumor showed concordance with a histopathological diagnosis
      (45.4% of cases). The most common alternate clinical diagnoses included lipoma,
      cyst, or angioma. A pathological diagnosis of glomus tumor was most common in the
      fourth to seventh decades of life. The most common presentation was a
      subcentimeter lesion on the digit. Deep-seated tumors had a strikingly increased
      risk for malignancy (33%). Radiological studies were not relied on frequently
      (18.2% of cases). Immunohistochemical analysis showed diffuse alphaSMA and MSA
      expression in nearly all cases (99% and 95%, respectively), with focal to diffuse
      CD34 immunostaining in 32% of cases. DISCUSSION: Our study illustrates trends in
      the clinical versus pathologic diagnoses of glomus tumor, common competing
      diagnoses, a difference in demographics than is commonly reported (older age
      groups most commonly affected), and important differences in the use adjunctive
      diagnostic tools including radiology and immunohistochemistry.

PMID- 25614466
TI  - Performance evaluation of automated urine microscopy as a rapid, non-invasive
      approach for the diagnosis of non-gonococcal urethritis.
AB  - OBJECTIVES: Gram-stained urethral smear (GSUS), the standard point-of-care test
      for non-gonococcal urethritis (NGU) is operator dependent and poorly specific.
      The performance of rapid automated urine flow cytometry (AUFC) of first void
      urine (FVU) white cell counts (UWCC) for predicting Mycoplasma genitalium and
      Chlamydia trachomatis urethral infections was assessed and its application to
      asymptomatic infection was evaluated. METHODS: Receiver operating characteristic
      curve analysis, determining FVU-UWCC threshold for predicting M. genitalium or C.
      trachomatis infection was performed on 208 'training' samples from symptomatic
      patients and subsequently validated using 228 additional FVUs obtained from
      prospective unselected patients. RESULTS: An optimal diagnostic threshold of >29
      UWC/uL gave sensitivities and specificities for either infection of 81.5% (95% CI
      65.1% to 91.6%) and 85.8% (79.5% to 90.4%), respectively, compared with 86.8%
      (71.1% to 95%) and 64.7% (56.9% to 71.7%), respectively, for GSUS, using the
      training set samples. FVU-UWCC demonstrated sensitivities and specificities of
      69.2% (95% CI 48.1% to 84.9%) and 92% (87.2% to 95.2%), respectively, when using
      validation samples. In asymptomatic patients where GSUS was not used, AUFC would
      have enabled more infections to be detected compared with clinical considerations
      only (71.4% vs 28.6%; p=0.03). The correlation between UWCC and bacterial load
      was stronger for M. genitalium compared with C. trachomatis (tau=0.426, p<=0.001
      vs tau=0.295, p=0.022, respectively). CONCLUSIONS: AUFC offers improved
      specificity over microscopy for predicting C. trachomatis or M. genitalium
      infection. Universal AUFC may enable non-invasive diagnosis of asymptomatic NGU
      at the PoC. The degree of urethral inflammation exhibits a stronger association
      with pathogen load for M. genitalium compared with C. trachomatis.

PMID- 25614467
TI  - Risk factors for selection of patients at high risk of recurrence or death after
      complete surgical resection in stage I gastric cancer.
AB  - BACKGROUND: The therapeutic benefit of adjuvant chemotherapy has not been proven
      in stage I gastric cancer (GC). The aim of this study was to identify stage I GC
      patients at high risk of recurrence or death. METHODS: We retrospectively
      reviewed the medical records of 2,783 patients with pathologically confirmed
      stage I GC who underwent curative surgical resection alone at Asan Medical Center
      between 2003 and 2007. The clinicopathologic parameters explored included age,
      sex, histologic differentiation, Lauren classification, size, location,
      multiplicity, stage, lymphovascular or perineural invasion, preoperative serum
      levels of tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9,
      carbohydrate antigen 72-4), and type of surgery. RESULTS: With a median follow-up
      of 54 months (range 0-60 months), 212 patients (7.6%) experienced recurrence or
      death, and the 5 -year recurrence-free survival (RFS) rate and overall survival
      rate were 89.9 and 93.4%, respectively. With a multivariate analysis, six factors
      (age over 65 years, male gender, stage IB GC, lymphovascular invasion, perineural
      invasion, and elevated level of carcinoembryonic antigen) were independent poor
      prognostic factors for RFS (p < 0.05). Patients with more than two of six poor
      risk factors had a 5-year RFS rate of 79%, whereas patients with fewer risk
      factors had a 5-year RFS rate of 97% (p <0.001). CONCLUSIONS: In this study
      cohort, we identified six independent risk factors for RFS. The patients with
      more than two risk factors are expected to have significant risk of recurrence or
      death after curative resection and should be considered as candidates for
      adjuvant treatment.

PMID- 25614469
TI  - Preeclampsia: an old disease with new tools for better diagnosis and risk
      management.

PMID- 25614468
TI  - Preoperative locoregional staging of gastric cancer: is there a place for
      magnetic resonance imaging? Prospective comparison with EUS and multidetector
      computed tomography.
AB  - BACKGROUND: The aim of this study was to prospectively compare the diagnostic
      performance of magnetic resonance imaging (MRI), multidetector computed
      tomography (MDCT) and endoscopic ultrasonography (EUS) in the preoperative
      locoregional staging of gastric cancer. METHODS: This study had Institutional
      Review Board approval, and informed consent was obtained from all patients. Fifty
      two patients with biopsy-proven gastric cancer underwent preoperative 1.5-T MRI,
      64-channel MDCT and EUS. All images were analysed blind, and the results were
      compared with histopathological findings according to the seventh edition of the
      TNM classification. After the population had been divided on the basis of the
      local invasion (T1-3 vs T4a-b) and nodal involvement (N0 vs N+), sensitivity,
      specificity, positive and negative predictive value, and accuracy were calculated
      and diagnostic performance measures were assessed using the McNemar test.
      RESULTS: For T staging, EUS showed higher sensitivity (94%) than MDCT and MRI (65
      and 76%; p = 0.02 and p = 0.08). MDCT and MRI had significantly higher
      specificity (91 and 89%) than EUS (60%) (p = 0.0009 and p = 0.003). Adding MRI to
      MDCT or EUS did not result in significant differences for sensitivity. For N
      staging, EUS showed higher sensitivity (92%) than MRI and MDCT (69 and 73%; p =
      0.01 and p = 0.02). MDCT showed better specificity (81%) than EUS and MRI (58 and
      73%; p = 0.03 and p = 0.15). CONCLUSIONS: Our prospective study confirmed the
      leading role of EUS and MDCT in the staging of gastric cancer and did not prove,
      at present, the value of the clinical use of MRI.

PMID- 25614470
TI  - The role of relatives in pathways to care of patients with a first episode of
      psychosis.
AB  - AIMS: To explore the role of relatives in pathways to care of patients with a
      recent onset of psychosis. METHODS: A total of 34 consecutive patients and their
      relatives from the Department of Psychiatry of the University of Naples SUN
      participated in the study. Pathways to care were retrospectively evaluated by
      administering the Pathways to Care Form and the Nottingham Onset Schedule (NOS)
      to patients, relatives and treating physicians. Relatives were addressed with the
      Family Involvement in Pathways to care Schedule (FIPS). RESULTS: Duration of
      untreated illness (DUI) and duration of untreated psychosis (DUP) were 145.4 (+/
      141.9) and 33.3 (+/-54.0) weeks, respectively. Help-seeking delay was 17.6 (+/
      45.0) weeks. The first request for help was made by relatives in 76% of cases.
      Among health professionals, general practitioners were those most frequently
      contacted, followed by psychiatrists, neurologists or psychologists. Stigma and
      wrong attribution of psychotic symptoms were the main reasons for help-seeking
      delays. CONCLUSIONS: Relatives play a crucial role in pathways to care of
      patients with psychosis. DUI and DUP could be reduced by interventions aimed at
      increasing knowledge of early symptoms in the general population, and by the
      provision of psychiatric consultations in non-stigmatizing settings for young
      people with psychological distress.

PMID- 25614471
TI  - Gaussian process test for high-throughput sequencing time series: application to
      experimental evolution.
AB  - MOTIVATION: Recent advances in high-throughput sequencing (HTS) have made it
      possible to monitor genomes in great detail. New experiments not only use HTS to
      measure genomic features at one time point but also monitor them changing over
      time with the aim of identifying significant changes in their abundance. In
      population genetics, for example, allele frequencies are monitored over time to
      detect significant frequency changes that indicate selection pressures. Previous
      attempts at analyzing data from HTS experiments have been limited as they could
      not simultaneously include data at intermediate time points, replicate
      experiments and sources of uncertainty specific to HTS such as sequencing depth.
      RESULTS: We present the beta-binomial Gaussian process model for ranking features
      with significant non-random variation in abundance over time. The features are
      assumed to represent proportions, such as proportion of an alternative allele in
      a population. We use the beta-binomial model to capture the uncertainty arising
      from finite sequencing depth and combine it with a Gaussian process model over
      the time series. In simulations that mimic the features of experimental evolution
      data, the proposed method clearly outperforms classical testing in average
      precision of finding selected alleles. We also present simulations exploring
      different experimental design choices and results on real data from Drosophila
      experimental evolution experiment in temperature adaptation. AVAILABILITY AND
      IMPLEMENTATION: R software implementing the test is available at
      https://github.com/handetopa/BBGP.

PMID- 25614472
TI  - Postoperative intraspinal subdural collections after pediatric posterior fossa
      tumor resection: incidence, imaging, and clinical features.
AB  - BACKGROUND AND PURPOSE: Postoperative intraspinal subdural collections in
      children after posterior fossa tumor resection may temporarily hinder metastasis
      detection by MR imaging or CSF analysis, potentially impacting therapy. We
      investigated the incidence, imaging and clinical features, predisposing factors,
      and time course of these collections after posterior fossa tumor resection.
      MATERIALS AND METHODS: Retrospective review of postoperative spine MRI in 243
      children (5.5 +/- 4.6 years of age) from our clinical data base postresection of
      posterior fossa tumors from October 1994 to August 2010 yielded 37 (6.0 +/- 4.8
      years of age) subjects positive for postoperative intraspinal subdural
      collections. Their extent and signal properties were recorded for postoperative
      (37/37), preoperative (15/37), and follow-up spine (35/37) MRI. Risk factors were
      compared with age-matched internal controls (n = 37, 5.9 +/- 4.5 years of age).
      Associations of histology, hydrocephalus and cerebellar tonsillar herniation, and
      postoperative intracranial subdural collections with postoperative intraspinal
      subdural collections were assessed by the Fisher exact test or chi(2) test. The
      association between preoperative tumor volume and postoperative intraspinal
      subdural collections was assessed by the Wilcoxon rank sum test. RESULTS: The
      overall incidence of postoperative intraspinal subdural collections was 37/243
      (15.2%), greatest <=7 days postoperatively (36%); 97% were seen 0-41 days
      postoperatively (12.9 +/- 11.0 days). They were T2 hyperintense and isointense to
      CSF on T1WI, homogeneously enhanced, and resolved on follow-up MR imaging
      (35/35). None were symptomatic. They were associated with intracranial subdural
      collections (P = .0011) and preoperative tonsillar herniation (P = .0228).
      CONCLUSIONS: Postoperative intraspinal subdural collections are infrequent and
      clinically silent, resolve spontaneously, and have a distinctive appearance.
      Preoperative tonsillar herniation appears to be a predisposing factor. In this
      series, repeat MR imaging by 4 weeks documented improvement or resolution of
      these collections in 88%.

PMID- 25614474
TI  - Correlation of the Patient Reported Outcomes Measurement Information System with
      legacy outcomes measures in assessment of response to lumbar transforaminal
      epidural steroid injections.
AB  - BACKGROUND AND PURPOSE: The Patient Reported Outcomes Measurement Information
      System is a newly developed outcomes measure promulgated by the National
      Institutes of Health. This study compares changes in pain and physical function
      related measures of this system with changes on the Numeric Rating Pain Scale,
      Roland Morris Disability Index, and the European Quality of Life scale 5D
      questionnaire in patients undergoing transformational epidural steroid injections
      for radicular pain. MATERIALS AND METHODS: One hundred ninety-nine patients
      undergoing transforaminal epidural steroid injections for radicular pain were
      enrolled in the study. Before the procedure, they rated the intensity of their
      pain by using the 0-10 Numeric Rating Pain Scale, Roland Morris Disability Index,
      and European Quality of Life scale 5D questionnaire. Patients completed the
      Patient Reported Outcomes Measurement Information System Physical Function, Pain
      Behavior, and Pain Interference short forms before transforaminal epidural
      steroid injections and at 3 and 6 months. Seventy and 43 subjects replied at 3-
      and 6-month follow-up. Spearman rank correlations were used to assess the
      correlation between the instruments. The minimally important differences were
      calculated for each measurement tool as an indicator of meaningful change.
      RESULTS: All instruments were responsive in detecting changes at 3- and 6-month
      follow-up (P < .0001). There was significant correlation between changes in
      Patient Reported Outcomes Measurement Information System scores and legacy
      questionnaires from baseline to 3 months (P < .05). There were, however, no
      significant correlations in changes from 3 to 6 months with any of the
      instruments. CONCLUSIONS: The studied Patient Reported Outcomes Measurement
      Information System domains offered responsive and correlative psychometric
      properties compared with legacy instruments in a population of patients
      undergoing transforaminal epidural steroid injections for radicular pain.

PMID- 25614473
TI  - Comparing 3T and 1.5T MRI for mapping hippocampal atrophy in the Alzheimer's
      Disease Neuroimaging Initiative.
AB  - BACKGROUND AND PURPOSE: Prior MR imaging studies, primarily at 1.5T, established
      hippocampal atrophy as a biomarker for Alzheimer disease. 3T MR imaging offers a
      higher contrast and signal-to-noise ratio, yet distortions and intensity
      uniformity are harder to control. We applied our automated hippocampal
      segmentation technique to 1.5T and 3T MR imaging data, to determine whether
      hippocampal atrophy detection was enhanced at 3T. MATERIALS AND METHODS: We
      analyzed baseline MR imaging data from 166 subjects from the Alzheimer's Disease
      Neuroimaging Initiative-1 (37 with Alzheimer disease, 76 with mild cognitive
      impairment, and 53 healthy controls) scanned at 1.5T and 3T. Using multiple
      linear regression, we analyzed the effect of clinical diagnosis on hippocampal
      radial distance, while adjusting for sex. 3D statistical maps were adjusted for
      multiple comparisons by using permutation-based statistics at a threshold of P <
      .01. RESULTS: Bilaterally significant radial distance differences in the areas
      corresponding to the cornu ammonis 1, cornu ammonis 2, and subiculum were
      detected for Alzheimer disease versus healthy controls and mild cognitive
      impairment versus healthy controls at 1.5T and more profoundly at 3T. Comparison
      of Alzheimer disease with mild cognitive impairment did not reveal significant
      differences at either field strength. Subjects who converted from mild cognitive
      impairment to Alzheimer disease within 3 years of the baseline scan versus
      nonconverters showed significant differences in the area corresponding to cornu
      ammonis 1 of the right hippocampus at 3T but not at 1.5T. CONCLUSIONS: While
      hippocampal atrophy patterns in diagnostic comparisons were similar at 1.5T and
      3T, 3T showed a superior signal-to-noise ratio and detected atrophy with greater
      effect size compared with 1.5T.

PMID- 25614475
TI  - Incidence of Inadvertent Intravascular Injection during CT Fluoroscopy-Guided
      Epidural Steroid Injections.
AB  - BACKGROUND AND PURPOSE: Inadvertent intravascular injection during epidural
      steroid injection can result in complications and has been investigated
      previously with conventional fluoroscopy, but not CT fluoroscopy. The purpose of
      this study was to determine the incidence of intravascular injections recognized
      during CT fluoroscopy-guided epidural steroid injection. MATERIALS AND METHODS:
      We retrospectively reviewed 575 consecutive CT fluoroscopy-guided epidural
      steroid injections. Procedures were assessed to determine the incidence of
      intravascular injection. Cases positive for intravascular injection were
      classified on the basis of anatomic location, distance from the needle tip,
      washout pattern, and presence of combined epidural and vascular injection. Cases
      were also graded as either venous or arterial by using a 5-point scale. RESULTS:
      Intravascular injection was observed in 26% of cervical transforaminal epidural
      steroid injections (7/27), 9% of cervical interlaminar epidural steroid
      injections (4/47), 8% of lumbar transforaminal epidural steroid injections
      (22/275), and 2% of lumbar interlaminar epidural steroid injections (4/222).
      Vessels were most commonly identified close to the needle, but in 30% of cases,
      they were visualized in the anterior paraspinal soft tissues remote from the
      needle. Washout was most commonly delayed (86%), though rapid washout occurred in
      14% of cases. Simultaneous epidural and vascular injections occurred in 32% of
      cases. Most visualized vessels were venous, but 2 cases were classified as
      probably arterial. CONCLUSIONS: Intravascular injections can be detected with CT
      fluoroscopy. The incidence in our study was similar to that in previous reports
      using conventional fluoroscopy. Technical factors such as the "double-tap" on CT
      fluoroscopy following contrast injection, assessment for discordance between
      injected and visualized contrast volume, and maintenance of an appropriate FOV
      facilitate the detection of such events.

PMID- 25614476
TI  - Reversible Cerebral Vasoconstriction Syndrome, Part 2: Diagnostic Work-Up,
      Imaging Evaluation, and Differential Diagnosis.
AB  - The diagnostic evaluation of a patient with reversible cerebral vasoconstriction
      syndrome integrates clinical, laboratory, and radiologic findings. Imaging plays
      an important role by confirming the presence of cerebral vasoconstriction;
      monitoring potential complications such as ischemic stroke; and suggesting
      alternative diagnoses, including CNS vasculitis and aneurysmal subarachnoid
      hemorrhage. Noninvasive vascular imaging, including transcranial Doppler
      sonography and MR angiography, has played an increasingly important role in this
      regard, though conventional angiography remains the criterion standard for the
      evaluation of cerebral artery vasoconstriction. Newer imaging techniques,
      including high-resolution vessel wall imaging, may help in the future to better
      discriminate reversible cerebral vasoconstriction syndrome from primary angiitis
      of the CNS, an important clinical distinction. 

PMID- 25614477
TI  - Evaluation of Virtual Noncontrast Images Obtained from Dual-Energy CTA for
      Diagnosing Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: The virtual noncontrast images generated with iodine
      subtraction from dual-energy CTA images are expected to replace the true
      noncontrast images for radiation-dose reduction. This study assessed the
      feasibility of virtual noncontrast images for diagnosing SAH. MATERIALS AND
      METHODS: Eighty-four patients with or without SAH underwent true noncontrast
      brain CT (the criterion standard for diagnosing SAH). Among them, 37 patients
      underwent an additional head dual-energy angiography, and the other patients
      underwent head and neck dual-energy angiography. Virtual noncontrast images were
      produced on a dedicated dual-energy postprocessing workstation and reconstructed
      in orientation and section width identical to those in true noncontrast images.
      The findings on the virtual noncontrast and true noncontrast images were compared
      at both the individual level and the lesion level. Image noise of the virtual
      noncontrast and true noncontrast images was also measured and compared. The
      volume CT dose index and dose-length product were recorded for the radiation-dose
      analysis. RESULTS: The sensitivity, specificity, positive predictive value, and
      negative predictive value of virtual noncontrast images at the individual level
      and the lesion level were 94.5%, 100%, 100%, 90.6% and 86.7%, 96.9%, 91.8%,
      94.8%, respectively. The agreement in the diagnosis of SAH on true noncontrast
      and virtual noncontrast images reached 92.3% at the individual level and 85.1% at
      the lesion level. The virtual noncontrast images showed a higher image noise
      level. The volume CT dose index and dose-length product were obviously reduced
      without the true noncontrast brain CT scan. CONCLUSIONS: Virtual noncontrast
      images are a reliable tool for diagnosing SAH, with the advantage of reducing the
      radiation dose.

PMID- 25614478
TI  - Reply: To PMID 24722310.

PMID- 25614479
TI  - Serum lactate dehydrogenase as a predictor of outcome in posterior reversible
      encephalopathy syndrome: imperative to unify.

PMID- 25614480
TI  - Assessment of spontaneous hemopneumothorax: Indications for surgery.
AB  - BACKGROUND: Although spontaneous hemopneumothorax is rare, emergency surgery may
      be necessary if massive bleeding is present. METHODS: We examined therapeutic
      strategies and outcomes as well as background factors in 16 patients with
      spontaneous hemopneumothorax treated at our hospital between April 2002 and
      August 2013. RESULTS: Emergency surgery was performed in 3 patients, all of whom
      were hemodynamically unstable. Elective surgery was performed in 7 patients, all
      of whom showed continuous bleeding from a pleural cavity drain. The surgery
      consisted of intrapleural hematoma removal, hemostasis, and bullectomy; 3-port
      thoracoscopy was used in all of the surgical cases. Six patients, none of whom
      showed continuous bleeding, recovered with conservative therapy. Comparing the
      conservative therapy and surgery groups revealed the mean continuous bleeding
      volume and total blood loss to be significantly greater in the latter, but no
      significant difference was noted between the two groups in terms of the initial
      bleeding volume following tube thoracostomy. None of the cases required a blood
      transfusion. CONCLUSIONS: Spontaneous hemopneumothorax is not necessarily an
      indication for surgery, and even when the initial volume of blood drained through
      the chest tube is large, some patients can still be treated conservatively with
      careful monitoring of vital signs and continuous bleeding volumes. However, it is
      important not to miss the optimal timing of surgery in order to avoid
      administering unnecessary blood transfusions to young patients.

PMID- 25614481
TI  - Spontaneous subclavian venous occlusion before electronic device implantation.
AB  - BACKGROUND: Subclavian venous occlusion sometimes precludes the ability to insert
      leads during placement of a cardiac implantable electronic device. This study was
      performed to identify the risk factors for spontaneous subclavian venous
      occlusion prior to placement of an implantable electronic device. METHODS: We
      studied 446 patients who underwent axillary-subclavian venography to assess for
      occlusion and/or anomaly of the subclavian vein or associated veins before
      electronic device implantation. RESULTS: Six (1.3%) patients had venous occlusion
      (left subclavian vein in 5, left innominate vein in 1). There was a significantly
      higher incidence of previous cancer in the occlusion group than in the
      nonocclusion group (11.5% vs. 50%, p = 0.03). CONCLUSIONS: Subclavian venous
      occlusion may be present before cardiac implantable electronic device placement.
      A history of cancer represents a risk factor subclavian venous occlusion, and
      patients with this risk factor should undergo subclavian venography prior to
      electronic device placement.

PMID- 25614482
TI  - A transition in fetal alcohol syndrome research: the shift from animal modeling
      to human intervention.

PMID- 25614485
TI  - A genetic platform to model sarcomagenesis from primary adult mesenchymal stem
      cells.
AB  - The regulatory factors governing adult mesenchymal stem cell (MSC) physiology and
      their tumorigenic potential are still largely unknown, which substantially delays
      the identification of effective therapeutic approaches for the treatment of
      aggressive and lethal forms of MSC-derived mesenchymal tumors, such as
      undifferentiated sarcomas. Here, we have developed a novel platform to screen and
      quickly identify genes and pathways responsible for adult MSC transformation,
      modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of
      targeting the identified oncopathways. Importantly, by taking advantage of this
      new platform, we demonstrate the key role of an aberrant LRF-DLK1-SOX9 pathway in
      the pathogenesis of undifferentiated sarcoma, with important therapeutic
      implications. SIGNIFICANCE: The paucity of therapeutic options for the treatment
      of sarcoma calls for a rapid and effective preclinical assessment of new
      therapeutic modalities. We have here developed a new platform to deconstruct the
      molecular genetics underlying the pathogenesis of sarcoma and to evaluate in vivo
      the efficacy of novel targeted therapies.

PMID- 25614490
TI  - Partial nephrectomy for hilar tumors: comparison of conventional open and robot
      assisted approaches.
AB  - BACKGROUND: To characterize clinical advantages in robot-assisted partial
      nephrectomy (RAPN) for targeting renal hilar tumors, and compare them with those
      of open PN (OPN). METHODS: This study included 31 consecutive patients with renal
      hilar tumors, consisting of 15 and 16 who received OPN and RAPN, respectively,
      between January 2012 and May 2014. The perioperative and oncological outcomes of
      the two approaches were compared. In this series, a hilar tumor was defined as a
      renal cortical tumor located in the renal hilum that was shown, by preoperative
      imaging, to be in direct physical contact with the renal artery and/or vein.
      RESULTS: There were no significant differences between demographic variables of
      the OPN and RAPN groups. Intended surgical procedures were successfully completed
      for all 31 cases. Despite lack of a significant difference between ischemia times
      in the two groups, operative time for RAPN was significantly longer than for OPN,
      and estimated blood loss during RAPN was significantly less than that during OPN.
      There were no significant differences between incidence of postoperative
      complications or percentage decrease in estimated glomerular filtration rate 4
      weeks after surgery in the two groups. Indicators of postoperative recovery
      seemed to favor RAPN compared with OPN, with significant differences. No patient
      in either group was pathologically diagnosed with a positive surgical margin.
      CONCLUSIONS: These findings suggest that, compared with OPN, RAPN is an
      effective, safe, and less invasive surgical option for renal hilar tumors.

PMID- 25614489
TI  - Synovial sarcoma: recent discoveries as a roadmap to new avenues for therapy.
AB  - Oncogenesis in synovial sarcoma is driven by the chromosomal translocation
      t(X,18; p11,q11), which generates an in-frame fusion of the SWI/SNF subunit SS18
      to the C-terminal repression domains of SSX1 or SSX2. Proteomic studies have
      identified an integral role of SS18-SSX in the SWI/SNF complex, and provide new
      evidence for mistargeting of polycomb repression in synovial sarcoma. Two recent
      in vivo studies are highlighted, providing additional support for the importance
      of WNT signaling in synovial sarcoma: One used a conditional mouse model in which
      knockout of beta-catenin prevents tumor formation, and the other used a small
      molecule inhibitor of beta-catenin in xenograft models. SIGNIFICANCE: Synovial
      sarcoma appears to arise from still poorly characterized immature mesenchymal
      progenitor cells through the action of its primary oncogenic driver, the SS18-SSX
      fusion gene, which encodes a multifaceted disruptor of epigenetic control. The
      effects of SS18-SSX on polycomb-mediated gene repression and SWI/SNF chromatin
      remodeling have recently come into focus and may offer new insights into the
      basic function of these processes. A central role for deregulation of WNT-beta
      catenin signaling in synovial sarcoma has also been strengthened by recent in
      vivo studies. These new insights into the the biology of synovial sarcoma are
      guiding novel preclinical and clinical studies in this aggressive cancer.

PMID- 25614491
TI  - Four plus forty-four: hours to modify, theirs to enjoy.

PMID- 25614493
TI  - The bioactive composite film prepared from bacterial cellulose and modified by
      hydrolyzed gelatin peptide.
AB  - The hydrolyzed gelatin peptides, obtained from the hydrolysis of Tilapia nilotica
      skin gelatin with alcalase and pronase E, were fractionated using an
      ultrafiltration system into hydrolyzed gelatin peptides-a (10 kDa membrane),
      hydrolyzed gelatin peptides-b1, and hydrolyzed gelatin peptides-b2 (5 kDa
      membrane) fractions. The highest oxygen radical absorbance capacity was observed
      in hydrolyzed gelatin peptides-b2, which contained more nonpolar amino acids than
      the other hydrolyzed gelatin peptides. Hydrolyzed gelatin peptides-b2 at a
      concentration of 12.5 mg/ml exhibited the highest proliferation ability and
      increased the expression of Type I procollagen mRNA, which indicated an enhanced
      collagen synthesis. Hydrolyzed gelatin peptides protected Detroit 551 cells from
      2,2'-azobis(2-amidinopropane) dihydrochloride-induced oxidative damage and
      increased cell viability. Hydroxylpropylmethyl cellulose-modified bacterial
      cellulose and dried fabricated biofilm were less eligible for Detroit 551 cell
      proliferation than bacterial cellulose. The release of hydrolyzed gelatin
      peptides in bacterial cellulose film was slower than that in hydroxylpropylmethyl
      cellulose-modified bacterial cellulose and dried fabricated biofilm; thus,
      bacterial cellulose film and hydroxylpropylmethyl cellulose-modified bacterial
      cellulose and dried fabricated biofilm are suitable candidates for applications
      in delayed release type and rapid release type biofilms, respectively.

PMID- 25614492
TI  - CKD in elderly patients managed without dialysis: survival, symptoms, and quality
      of life.
AB  - BACKGROUND AND OBJECTIVES: Survival, symptom burden, and quality of life (QOL)
      are uncertain for elderly patients with advanced CKD managed without dialysis. We
      examined these outcomes in patients managed with renal supportive care without
      dialysis (RSC-NFD) and those planned for or commencing dialysis. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: In this prospective observational study, symptoms
      were measured using the Memorial Symptom Assessment Scale and the Palliative care
      Outcomes Scale - Symptoms (renal) inventory and QOL was measured using the Short
      Form-36 survey. This study comprised 273 predialysis patients who had usual
      nephrology care and 122 nondialysis pathway patients who also attended a renal
      supportive care clinic adding the skills of a palliative medicine team. A further
      72 patients commenced dialysis during this period without attending either
      clinic. RESULTS: Nondialysis patients were older than the predialysis group (82
      versus 67 years; P<0.001) but had similar eGFR at the first clinic visit (16
      ml/min per 1.73 m(2); P=0.92). Of the predialysis patients, 92 (34%) commenced
      dialysis. Compared with the RSC-NFD group, the death rate was lower in the
      predialysis group who did not require dialysis (hazard ratio, 0.23; 95%
      confidence interval, 0.12 to 0.41] and in those requiring dialysis (0.30; 0.13 to
      0.67) but not in dialysis patients who had not attended the predialysis clinic
      (0.60; 0.35 to 1.03). Median survival in RSC-NFD patients was 16 (interquartile
      range, 9, 37) months and 32% survived >12 months after eGFR fell below 10 ml/min
      per 1.73 m(2). For the whole group, age, serum albumin, and eGFR <15 ml/min per
      1.73 m(2) were associated with poorer survival. Of the nondialysis patients, 57%
      had stable or improved symptoms over 12 months and 58% had stable or improved
      QOL. CONCLUSIONS: Elderly patients who choose not to have dialysis as part of
      shared decision making survive a median of 16 months and about one-third survive
      12 months past a time when dialysis might have otherwise been indicated.
      Utilizing the skills of palliative medicine helps provide reasonable symptom
      control and QOL without dialysis.

PMID- 25614494
TI  - Comparison of prasugrel and clopidogrel-treated patients with acute coronary
      syndrome undergoing percutaneous coronary intervention: A propensity score
      matched analysis of the Acute Myocardial Infarction in Switzerland (AMIS)-Plus
      Registry.
AB  - OBJECTIVE: The purpose of this study was to investigate outcomes of patients
      treated with prasugrel or clopidogrel after percutaneous coronary intervention
      (PCI) in a nationwide acute coronary syndrome (ACS) registry. BACKGROUND:
      Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS
      patients undergoing PCI. However, little is known about its efficacy in everyday
      practice. METHODS: All ACS patients enrolled in the Acute Myocardial Infarction
      in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a
      thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included
      in this analysis. Patients were stratified according to treatment with prasugrel
      or clopidogrel and outcomes were compared using propensity score matching. The
      primary endpoint was a composite of death, recurrent infarction and stroke at
      hospital discharge. RESULTS: Out of 7621 patients, 2891 received prasugrel (38%)
      and 4730 received clopidogrel (62%). Independent predictors of in-hospital
      mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and
      resuscitation prior to admission. After propensity score matching (2301 patients
      per group), the primary endpoint was significantly lower in prasugrel-treated
      patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1%
      vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%;
      p=0.004), but no significant differences were observed in rates of recurrent
      infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a
      predefined subset of matched patients with one-year follow-up (n=1226), mortality
      between discharge and one year was not significantly reduced in prasugrel-treated
      patients (1.3% vs 1.9%, p=0.38). CONCLUSIONS: In everyday practice in
      Switzerland, prasugrel is predominantly used in younger patients with STEMI
      undergoing primary PCI. A propensity score-matched analysis suggests a mortality
      benefit from prasugrel compared with clopidogrel in these patients.

PMID- 25614495
TI  - Prevention and management of foot complications in patients with diabetes: an
      interdisciplinary care perspective.

PMID- 25614496
TI  - Guest editorial.

PMID- 25614497
TI  - Sensory manifestations of diabetic neuropathies: anatomical and clinical
      correlations.
AB  - BACKGROUND: Diabetes mellitus is among the most common causes of peripheral
      neuropathy worldwide. Sensory impairment in diabetics is a major risk factor of
      plantar ulcers and neurogenic arthropathy (Charcot joints) causing severe
      morbidity and high health-care costs. OBJECTIVE: To discuss the different
      patterns of sensory alterations in diabetic neuropathies and their anatomical
      basis. STUDY DESIGN: Literature review. METHODS: Review of the literature
      discussing different patterns of sensory impairment in diabetic neuropathies.
      RESULTS: The different varieties of diabetic neuropathies include typical
      sensorimotor polyneuropathy (lower extremity predominant, length-dependent,
      symmetric, sensorimotor polyneuropathy presumably related to chronic
      hyperglycemic exposure, and related metabolic events), entrapment
      mononeuropathies, radiculoplexus neuropathies related to immune inflammatory
      ischemic events, cranial neuropathies, and treatment-related neuropathies (e.g.
      insulin neuritis). None of these patterns are unique for diabetes, and they can
      occur in nondiabetics. Sensory alterations are different among these prototypic
      varieties and are vital in diagnosis, following course, treatment options, and
      follow-up of treatment effects. CONCLUSIONS: Diabetic neuropathies can involve
      any segment of peripheral nerves from nerve roots to the nerve endings giving
      different patterns of abnormal sensation. It is the involvement of small fibers
      that causes positive sensory symptoms like pain early during the course of
      disease, bringing subjects to physician's care. CLINICAL RELEVANCE: This article
      emphasizes on the fact that diabetic neuropathies are not a single entity. They
      are rather different varieties of conditions with more or less separate
      pathophysiological mechanisms and anatomical localization. Clinicians should keep
      this in mind when assessing patients with diabetes on the first visit or follow
      up.

PMID- 25614498
TI  - Treatment of painful diabetic peripheral neuropathy.
AB  - BACKGROUND: Painful diabetic peripheral neuropathy impairs quality of life and
      can be difficult to treat. OBJECTIVE: To discuss current treatment
      recommendations for painful diabetic peripheral neuropathy. STUDY DESIGN:
      Literature review. METHODS: Systematic review of the literature discussing
      treatment of painful diabetic peripheral neuropathy. Existing treatment
      guidelines were studied and compared. RESULTS: Painful diabetic peripheral
      neuropathy occurs in about one in six people with diabetes. This condition
      impairs quality of life and increases healthcare costs. Treatment recommendations
      exist, but individual patient therapy can require a trial-and-error approach.
      Many treatment options have adjuvant benefits or side effects which should be
      considered prior to initiating therapy. Often, a combination of treatment
      modalities with various mechanisms of action is required for adequate pain
      control. Adequate medication titration and a reasonable trial period should be
      allowed. CONCLUSION: The treatment of painful diabetic peripheral neuropathy can
      be challenging, but effective management can improve patient's quality of life.
      CLINICAL RELEVANCE: Painful diabetic peripheral neuropathy impairs quality of
      life and can be difficult to treat. Many treatment options have adjuvant benefits
      or side effects which should be considered prior to initiating therapy. Often, a
      combination of treatment modalities with various mechanisms of action is required
      for adequate pain control.

PMID- 25614499
TI  - Wound management of chronic diabetic foot ulcers: from the basics to regenerative
      medicine.
AB  - BACKGROUND: Hospital-based studies have shown that mortality rates in individuals
      with diabetic foot ulcers are about twice those observed in individuals with
      diabetes without foot ulcers. OBJECTIVE: To assess the etiology and management of
      chronic diabetic foot ulcers. STUDY DESIGN: Literature review. METHODS:
      Systematic review of the literature discussing management of diabetic foot
      ulcers. Since there were only a few randomized controlled trials on this topic,
      articles were selected to attempt to be comprehensive rather than a formal
      assessment of study quality. RESULTS: Chronic nonhealing foot ulcers occur in
      approximately 15% of patients with diabetes. Many factors contribute to impaired
      diabetic wound healing. Risk factors include peripheral neuropathy, peripheral
      arterial disease, limited joint mobility, foot deformities, abnormal foot
      pressures, minor trauma, a history of ulceration or amputation, and impaired
      visual acuity. With the current treatment for nonhealing diabetic foot ulcers, a
      significant number of patients require amputation. CONCLUSION: Diabetic foot
      ulcers are optimally managed by a multidisciplinary integrated team. Offloading
      and preventative management are important. Dressings play an adjunctive role.
      There is a critical need to develop novel treatments to improve healing of
      diabetic foot ulcers. The goal is to have wounds heal and remain healed. CLINICAL
      RELEVANCE: Diabetic neuropathy and peripheral arterial disease are major factors
      involved in a diabetic foot ulcer. Despite current treatment modalities for
      nonhealing diabetic foot ulcers, there are a significant number of patients who
      require amputations. No known therapy will be effective without concomitant
      management of ischemia, infection, and adequate offloading.

PMID- 25614500
TI  - Pedorthic management of the diabetic foot.
AB  - BACKGROUND: Conservative pedorthic management of the diabetic foot has been shown
      to be an effective method to prevent ulcers, amputations, and re-amputations.
      This article exhibits why and how pedorthics plays such an important role via
      modalities such as footwear, shoe modifications, custom foot orthoses, and
      partial foot prostheses. OBJECTIVE: The objective of this article is to
      demonstrate how pedorthics has been shown to be an integral part of conservative
      diabetic foot care. The authors' goal was to educate the reader about the
      different modalities that are available for use. STUDY DESIGN: This article is
      based largely on review of previously published research and scholarly articles,
      augmented by the more than 60 years of pedorthic and orthotic clinical experience
      of the authors. METHODS: Approximately 60 journal articles and book chapters were
      reviewed by the authors. Articles were located via online resources such as
      PubMed as well as the authors' own libraries. RESULTS: It was repeatedly noted
      that pedorthic modalities such as shoes, foot orthoses, and shoe modifications
      may be utilized in the treatment and prevention of diabetic foot wounds and other
      complications. CONCLUSION: Pedorthic devices may be successfully integrated into
      a comprehensive treatment plan for patients with diabetes and foot ulcers.
      CLINICAL RELEVANCE: This information is of special interest to those who treat
      patients with diabetes. The article demonstrates the efficacy of pedorthic
      intervention through the compilation and review of relevant previously published
      data.

PMID- 25614501
TI  - BE SMART: strategies for foot care and prevention of foot complications in
      patients with diabetes.
AB  - BACKGROUND: Diabetic foot ulcers and lower extremity amputations are common
      complications of diabetes mellitus that are associated with substantial
      morbidity, loss of quality of life, disability, and a high social and economic
      burden. The implementation of strategies to prevent these complications is a key
      aspect of diabetes care. OBJECTIVES: The objective of this article is to provide
      an overview of the available evidence on preventive diabetic foot care. STUDY
      DESIGN: Literature review. METHODS: Narrative review based on a thorough search
      of previous relevant studies, systematic reviews, and clinical guidelines on
      diabetic foot care published in English. RESULTS: We describe diabetic foot care
      strategies that can be categorized within defined domains for the purpose of
      helping clinicians to remember them. We use the mnemonic "BE SMART" (Be aware of
      the risk factors, Educate patients and health providers, Structured clinical
      assessment, Metabolic evaluation and management, Assessment of Risk, and Team
      care) to organize these domains. CONCLUSION: Diabetic foot ulcers and lower
      extremity amputations are potentially preventable complications. Clinicians
      taking care of patients with diabetes should know, understand, and remember the
      multiple aspects of diabetic foot care. CLINICAL RELEVANCE: This review can be
      used as a reference source for those interested in the care of diabetic foot. It
      highlights the importance of risk factor recognition, education, a structured
      clinical and metabolic evaluation, and also the importance of assigning patients
      a risk category that can help guiding multidisciplinary management efforts.

PMID- 25614502
TI  - Surgical management of Charcot neuroarthropathy.
AB  - BACKGROUND: Charcot neuroarthropathy is one of the more devastating complications
      of diabetes. It is a progressive, destructive condition that is characterized by
      acute fracture, dislocation, and joint destruction in weight-bearing neuropathic
      foot. In its acute phase, it is often misdiagnosed and can lead to several
      deformities such as ulcerations and amputation. Early diagnosis and management
      is, therefore, imperative to avoid rapid progression. OBJECTIVES: Review current
      literature on the diagnosis and management of diabetic patients with Charcot
      neuroarthropathy. STUDY DESIGN: Narrative review. METHODS: Particular attention
      is directed to the role of surgical management in achieving long term osseous
      stability and alignment so that appropriate footwear and bracing are possible.
      CONCLUSION: Charcot neuroarthropathy is a serious and potentially limb
      threatening lower extremity late complication of diabetes. Correct timing,
      adequate fixation and a long post-operative weightbearing period are key to
      optimizing reconstructive surgery. CLINICAL RELEVANCE: Primary care providers who
      treat diabetic patients should be cognizant of the possible complication among
      patients with diabetic neuropathy of which includes Charcot neuroarthropathy. In
      this paper, discussion is provided on a rational approach to functional limb
      salvage with various surgical techniques when non-operative management fails.

PMID- 25614503
TI  - Orthotic management of the neuropathic foot: an interdisciplinary care
      perspective.
AB  - BACKGROUND: Clinical management of the patient with neuropathic foot is becoming
      commonplace in orthotic clinics worldwide. The presentations that can result from
      neuropathic foot are diverse, requiring clinicians to understand the
      pathomechanics of ulceration, infection, and Charcot joint arthropathy to provide
      effective interventions. OBJECTIVES: The purpose of this clinical perspective is
      to provide a review of the literature regarding clinical concepts associated with
      orthotic management of neuropathic foot. STUDY DESIGN: Literature review and
      clinical case study. METHODS: Relevant literature were reviewed and summarized,
      and a clinical case study synthesizing reviewed concepts was presented. RESULTS:
      Given the multifactorial nature of the neuropathic foot, treatments must be
      multifaceted and patient-specific to effectively address the underlying disease
      processes. While systemic issues such as peripheral arterial disease are treated
      by physicians, local issues such as foot deformity are managed by orthotists.
      Orthotic interventions commonly include custom footwear to reduce the risk of
      ulceration through creation of a protective environment or targeted plantar
      offloading. Patient and caregiver education to encourage management compliance is
      equally as important to ensure successful treatment. CONCLUSION: Patients with
      neuropathic foot benefit from an interdisciplinary care approach which engages
      physicians, wound care practitioners, and orthotists to treat and manage systemic
      and local problems. Addressing this pathology through interdisciplinary care may
      positively affect the patient's health status while lowering associated
      healthcare costs through improved treatment efficacy. CLINICAL RELEVANCE: The
      commonality of neuropathic foot and associated complications including
      ulceration, infection, and Charcot joint arthropathy requires that the patient
      care team have a fundamental understanding of these pathologies and common
      treatment modalities. We review orthotic treatment modalities to assist
      clinicians with the management of patients with neuropathic foot.

PMID- 25614504
TI  - The mechanism of soft tissue damage: It is all in the rub.
AB  - Understanding mechanisms of injury to the skin and soft tissue are an important
      feature in optimizing management strategies. As technology advances and
      innovative wound products evolve, the need for the awareness of such developments
      is key to enhancing knowledge and their clinical application. This article
      provides an overview of the role of repetitive loading of the skin and tissues
      and the influence of thickness and mobility of these structures. The role of
      friction and pressure strategies is also discussed along with a brief overview of
      new products. CLINICAL RELEVANCE: Pressure and friction are important parameters
      in the management of wounds. Clinicians should be aware of these concepts and be
      cognizant of new technologies that are available for the reduction of these
      parameters.

PMID- 25614505
TI  - Addressing the right targets in oncology: challenges and alternative approaches.
AB  - Translating existing and emerging knowledge of cancer biology into effective
      novel therapies remains a great challenge in drug discovery. A firm understanding
      of the target biology, confidence in the supporting preclinical research, and
      access to diverse chemical matter is required to lower attrition rates and
      prosecute targets effectively. Understanding past successes and failures will aid
      in refining this process to deliver further therapeutic benefit to patients. In
      this review, we suggest that early oncology drug discovery should focus on
      selection and prosecution of cancer targets with strong disease biology rather
      than on more chemically "druggable" targets with only modest disease-linkage.
      This approach offers higher potential benefit but also increases the need for
      innovative and alternative approaches. These include using different methods to
      validate novel targets and identify chemical matter, as well as raising the
      standards and our interpretation of the scientific literature. The combination of
      skills required for this emphasizes the need for broader early collaborations
      between academia and industry. 

PMID- 25614506
TI  - How to successfully patent therapeutic antibodies.
AB  - Therapeutic antibodies have become an established class of drugs for the
      treatment of a variety of diseases, especially cancer and autoimmune/inflammatory
      disorders, and a sufficient patent protection is a prerequisite for their
      successful commercialization. As monoclonal antibodies and their therapeutic
      potential have been well known for decades, the mere production of yet another
      therapeutic antibody is in many jurisdictions not considered a patentable
      invention. In contrast, antibodies with novel structural features and/or improved
      properties may be patentable. When drafting the claims, care should be taken to
      obtain a broad patent scope that protects both the antibody of interest and
      related antibodies having the same functional features, thereby preventing
      competitors from marketing a functionally equivalent antibody. Furthermore, the
      application should contain experimental evidence showing the improved properties
      of the claimed antibody. After the filing of a priority patent application,
      patent protection should be initiated at least in countries that are of
      particular commercial importance. Subsequent inventions relating to novel uses,
      formulations, dosage regimens, and combinations with other treatment modalities
      should be protected by further patent applications to extend patent term. 

PMID- 25614507
TI  - Personalized technology to support older adults with and without cognitive
      impairment living at home.
AB  - Although persons with dementia (PWD) and their family caregivers need in-home
      support for common neuropsychiatric symptoms (NPS), few if any assistive
      technologies are available to help manage NPS. This implementation study tested
      the feasibility and adoption of a touch screen technology, the Companion, which
      delivers psychosocial, nondrug interventions to PWD in their home to address
      individual NPS and needs. Interventions were personalized and delivered in home
      for a minimum of 3 weeks. Postintervention measures indicated the technology was
      easy to use, significantly facilitated meaningful and positive engagement, and
      simplified caregivers' daily lives. Although intervention goals were met,
      caregivers had high expectations of their loved one's ability to regain
      independence. Care recipients used the system independently but were limited by
      cognitive and physical impairments. We conclude the Companion can help manage NPS
      and offer caregiver respite at home. These data provide important guidance for
      design and deployment of care technology for the home. 

PMID- 25614509
TI  - The Selfish Gene, introduced the term 'meme' to describe a verbally transmitted
      cultural idea.

PMID- 25614508
TI  - Melatonin for sleep disorders and cognition in dementia: a meta-analysis of
      randomized controlled trials.
AB  - The current review aims to examine melatonin therapy for both sleep disturbances
      and cognitive function in dementia. We searched all randomized controlled trials
      published in Medline, Embase, the Cochrane Library, China National Knowledge
      Infrastructure, the Cochrane Dementia and Cognitive Improvement Group's
      Specialized Register, and Clinical Trials.gov. The grading of recommendations
      assessment, development and evaluation framework was used to assess the quality
      of evidence. Seven studies were included (n = 520). Treated participants showed
      prolonged total sleep time (TST) by 24.36 minutes (P = .02). Sleep efficacy (SE)
      was marginally improved (P = .07). This effect was stronger under a longer
      intervention period lasting more than 4 weeks (P = .02). Conversely, cognitive
      function did not change significantly. Additionally, there was no report of
      severe adverse events. Given the current studies, we conclude that melatonin
      therapy may be effective in improving SE and prolonging TST in patients with
      dementia; however, there is no evidence that this improvement impacts cognitive
      function.

PMID- 25614512
TI  - Improving the Rate of Colposcopy in an Urban Population of Patients With Known
      Abnormal Pap Smears.
AB  - This project was designed to improve the colposcopy rate in an urban patient
      population with known abnormal Pap smears within 75 days of the test to rapidly
      identify and treat premalignant lesions. Using Plan-Do-Study-Act cycles, Lean
      techniques, and the electronic health record, the authors created a protocol to
      verify all Pap smears, then created a process whereby a phone-triage team
      contacted patients with abnormal Pap smears to educate them and schedule
      colposcopy. As a result, 100% of Pap smears were verified, compared with 95%
      prior to plan implementation. The mean time from Pap to colposcopy was 38.5 days,
      with 85% of patients having colposcopy performed after plan implementation,
      compared with 50% prior-a 70% improvement. If patients with medical
      contraindications were excluded, the percentage rose to 91%-an 82% improvement.
      Patient and provider satisfaction improved, staff and provider workload did not
      increase, and there was the potential for substantial economic savings.

PMID- 25614511
TI  - Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and
      Enhances Response to Other Immunomodulatory Therapies.
AB  - Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 (PLXNB1) are broadly
      expressed in murine and human tumors, and their expression has been shown to
      correlate with invasive disease in several human tumors. SEMA4D normally
      functions to regulate the motility and differentiation of multiple cell types,
      including those of the immune, vascular, and nervous systems. In the setting of
      cancer, SEMA4D-PLXNB1 interactions have been reported to affect vascular
      stabilization and transactivation of ERBB2, but effects on immune-cell
      trafficking in the tumor microenvironment (TME) have not been investigated. We
      describe a novel immunomodulatory function of SEMA4D, whereby strong expression
      of SEMA4D at the invasive margins of actively growing tumors influences the
      infiltration and distribution of leukocytes in the TME. Antibody neutralization
      of SEMA4D disrupts this gradient of expression, enhances recruitment of activated
      monocytes and lymphocytes into the tumor, and shifts the balance of cells and
      cytokines toward a proinflammatory and antitumor milieu within the TME. This
      orchestrated change in the tumor architecture was associated with durable tumor
      rejection in murine Colon26 and ERBB2(+) mammary carcinoma models. The
      immunomodulatory activity of anti-SEMA4D antibody can be enhanced by combination
      with other immunotherapies, including immune checkpoint inhibition and
      chemotherapy. Strikingly, the combination of anti-SEMA4D antibody with antibody
      to CTLA-4 acts synergistically to promote complete tumor rejection and survival.
      Inhibition of SEMA4D represents a novel mechanism and therapeutic strategy to
      promote functional immune infiltration into the TME and inhibit tumor
      progression.

PMID- 25614513
TI  - The Armstrong Institute Resident/Fellow Scholars: A Multispecialty Curriculum to
      Train Future Leaders in Patient Safety and Quality Improvement.
AB  - The objective was to determine if a year-long, multispecialty resident and fellow
      quality improvement (QI) curriculum is feasible and leads to improvements in QI
      beliefs and self-reported behaviors. The Armstrong Institute Resident/Fellow
      Scholars (AIRS) curriculum incorporated (a) a 2-day workshop in lean sigma
      methodology, (b) year-long interactive weekly small-group lectures, (c) mentored
      QI projects, and (d) practicum-based components to observe frontline QI efforts.
      Pre-post evaluation was performed with the Quality Improvement Knowledge
      Application Tool (QIKAT) and the Systems Thinking Scale (STS) using the Wilcoxon
      matched-pairs signed-rank test. Sixteen residents and fellows started the AIRS
      curriculum and 14 finished. Scholars' pre and post mean scores significantly
      improved: STS 3.06 pre versus 3.60 post (P < .01) and QIKAT 1.24 pre versus 2.46
      post (P < .01). Most scholars (92%) agreed that skills learned in the curriculum
      will help in their future careers. A multispecialty QI curriculum for trainees is
      feasible and increases QI beliefs and self-reported behaviors.

PMID- 25614514
TI  - All-trans-retinoic acid inhibition of transforming growth factor-beta-induced
      collagen gel contraction mediated by human Tenon fibroblasts: role of matrix
      metalloproteinases.
AB  - BACKGROUND/AIMS: Scarring and contraction of the conjunctiva are common
      complications of many ocular diseases. We investigated the effects of all-trans
      retinoic acid (ATRA) on the contractility of human Tenon's capsule fibroblasts
      (HTFs) cultured in a three-dimensional collagen gel. METHODS: HTFs were cultured
      in a three-dimensional gel of type I collagen and in the absence or presence of
      transforming growth factor (TGF)-beta, ATRA, or an inhibitor of matrix
      metalloproteinases (MMPs). Collagen gel contraction was evaluated by measurement
      of gel diameter. The release of MMPs and tissue inhibitors of metalloproteinases
      (TIMPs) into culture supernatants was assessed by immunoblot analysis and gelatin
      zymography. The release of lactate dehydrogenase activity from HTFs was measured
      with a colorimetric assay kit. RESULTS: ATRA inhibited TGF-beta-induced collagen
      gel contraction mediated by HTFs in a concentration- and time-dependent manner.
      TGF-beta induced the release of MMP-1, MMP-2 and MMP-3 by HTFs, and ATRA
      inhibited these effects of TGF-beta on MMP-1 and MMP-3 release. ATRA also
      stimulated TIMP-1 release from HTFs in the presence of TGF-beta. Furthermore, TGF
      beta-induced collagen gel contraction was blocked by the MMP inhibitor GM6001.
      ATRA did not exhibit cytotoxicity for HTFs. CONCLUSIONS: ATRA inhibited TGF-beta
      induced collagen gel contraction mediated by HTFs, likely in part by attenuating
      the production of MMP-1 and MMP-3 and by stimulating the production of TIMP-1.
      ATRA may therefore prove to be of clinical value for inhibition of scar formation
      in the conjunctiva.

PMID- 25614515
TI  - Peripapillary choroidal thickness assessed using automated choroidal segmentation
      software in an Asian population.
AB  - AIMS: To objectively quantify the thickness of peripapillary choroid using
      spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging
      (EDI) followed by a novel automated choroidal segmentation software in Asian eyes
      and to evaluate its systemic and ocular determinants. METHODS: We recruited 520
      subjects (1040 eyes) from the Singapore Malay Eye Study, a cross-sectional
      population-based study. Subjects underwent standardised detailed ophthalmic
      examination including SD-OCT (Spectralis) with EDI for measurement of
      peripapillary choroidal thickness (PPCT). RESULTS: The mean age of the subjects
      was 66.7+/-10.4 years (range 47-88 years) and the mean spherical equivalent was 
      0.01+/-2.28 D (range -18.50 to +7.00 D). The intra-session repeatability of PPCT
      measurements at four quadrants using automated choroidal segmentation software
      was excellent (intraclass correlation coefficient 0.9998-0.9999). The overall
      mean PPCT was 136.2+/-56.8 um. Peripapillary choroid showed geographical
      differences among the four quadrants, being thickest in the superior quadrant
      (150.5+/-59.6 um), followed by the nasal (143.5+/-58.4 um) and temporal quadrants
      (139.4+/-68.9 um), and thinnest in the inferior quadrant (111.3+/-51.7 um). Among
      the range of ocular and systemic factors studied, shorter axial length (p=0.002),
      younger age (p=0.018), lower triglyceride level (p=0.015) and the presence of
      diabetes (p=0.036) were the only significant predictors of thicker peripapillary
      choroid. CONCLUSIONS: Using novel automated choroidal segmentation software, we
      provide reliable objective measurements of PPCT in a population-based setting.
      Shorter axial length, younger age, lower triglyceride levels and the presence of
      diabetes are the factors independently associated with thicker PPCT. These
      factors should be taken into consideration when interpreting Spectralis EDI SD
      OCT-based PPCT measurements in clinics.

PMID- 25614516
TI  - Cell division patterns in acute myeloid leukemia stem-like cells determine
      clinical course: a model to predict patient survival.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease in which a variety of
      distinct genetic alterations might occur. Recent attempts to identify the
      leukemia stem-like cells (LSC) have also indicated heterogeneity of these cells.
      On the basis of mathematical modeling and computer simulations, we have provided
      evidence that proliferation and self-renewal rates of the LSC population have
      greater impact on the course of disease than proliferation and self-renewal rates
      of leukemia blast populations, that is, leukemia progenitor cells. The modeling
      approach has enabled us to estimate the LSC properties of 31 individuals with
      relapsed AML and to link them to patient survival. On the basis of the estimated
      LSC properties, the patients can be divided into two prognostic groups that
      differ significantly with respect to overall survival after first relapse. The
      results suggest that high LSC self-renewal and proliferation rates are indicators
      of poor prognosis. Nevertheless, high LSC self-renewal rate may partially
      compensate for slow LSC proliferation and vice versa. Thus, model-based
      interpretation of clinical data allows estimation of prognostic factors that
      cannot be measured directly. This may have clinical implications for designing
      treatment strategies.

PMID- 25614520
TI  - Summary and highlights from the International Union against Sexually Transmitted
      Infections Congress 2014, Malta.

PMID- 25614519
TI  - Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in
      patients with HIV and cryptococcal meningitis: a diagnostic challenge.
AB  - Patients with HIV are at risk of both primary and secondary haematological
      disorders. We report two cases of patients with HIV and cryptococcal meningitis
      who developed severe haemolytic anaemia, thrombocytopenia, renal failure and
      lactic acidosis while on treatment with amphotericin B and co-trimoxazole. 

PMID- 25614517
TI  - Starvation promotes REV1 SUMOylation and p53-dependent sensitization of melanoma
      and breast cancer cells.
AB  - Short-term starvation or fasting can augment cancer treatment efficacy and can be
      effective in delaying cancer progression in the absence of chemotherapy, but the
      underlying molecular mechanisms of action remain elusive. Here, we describe the
      role of REV1, a specialized DNA polymerase involved in DNA repair, as an
      important signaling node linking nutrient sensing and metabolic control to cell
      fate. We show that REV1 is a novel binding partner of the tumor suppressor p53
      and regulates its activity. Under starvation, REV1 is modified by SUMO2/3,
      resulting in the relief of REV1's inhibition of p53 and enhancing p53's effects
      on proapoptotic gene expression and apoptosis in breast cancer and melanoma
      cells. Thus, fasting in part through its effect on REV1 is a promising nontoxic
      strategy to increase p53-dependent cell death and to enhance the efficacy of
      cancer therapies.

PMID- 25614521
TI  - Non-healing genital herpes mimicking donovanosis in an immunocompetent man.
AB  - Although atypical presentations of herpetic infection in immunocompetent
      individuals are common, they very rarely have the extensive, chronic and
      verrucous appearances seen in the immunocompromised host. We report a case of
      genital herpes manifesting as painless chronic non-healing genital ulcers with
      exuberant granulation tissue in an immunocompetent man. Owing to this morphology,
      the ulcers were initially mistaken for donovanosis. To the best of our knowledge,
      such a presentation of genital herpes in an immunocompetent individual has not
      been described previously. 

PMID- 25614522
TI  - Genital infections and syndromic diagnosis among HIV-infected women in HIV care
      programmes in Kenya.
AB  - Control of genital infections remains challenging in most regions. Despite
      advocacy by the World Health Organization for syndromic case management, there
      are limited data on the syndromic approach, especially in HIV care settings. This
      study compared the syndromic approach with laboratory diagnosis among women in
      HIV care in Kenya. A mobile team visited 39 large HIV care programmes in Kenya
      and enrolled participants using population-proportionate sampling. Participants
      provided behavioural and clinical data with genital and blood specimens for lab
      testing. Among 1063 women, 68.4% had been on antiretroviral therapy >1 year;
      58.9% were using cotrimoxazole prophylaxis; 51 % had CD4+T-lymphocytes < 350
      cells/uL. Most women (63.1%) reported at least one genital symptom. Clinical
      signs were found in 63% of women; and 30.8% had an aetiological diagnosis.
      Bacterial vaginosis (17.4%), vaginal candidiasis (10.6%) and trichomoniasis
      (10.5%) were the most common diagnoses. Using laboratory diagnoses as gold
      standard, sensitivity and positive predictive value of the syndromic diagnosis
      for vaginal discharge were 47.6% and 52.7%, respectively, indicating a
      substantial amount of overtreatment. A systematic physical examination increased
      by 9.3% the positive predictive value for genital ulcer disease. Women attending
      HIV care programmes in Kenya have high rates of vaginal infections. Syndromic
      diagnosis was a poor predictor of those infections. 

PMID- 25614524
TI  - Attitude of patients with HIV infection towards organ transplant between HIV
      patients. A cross-sectional questionnaire survey.
AB  - This study examined the HIV patients' attitudes towards the practice of organ
      transplant between HIV patients using a cross-sectional survey design. In total,
      206 patients participated with a mean age of 42 (+/-8.8) years. The majority
      (70%) were black African and women (54%), and 83% described themselves as
      heterosexual. Most participants (n = 171, 83%) were on treatment, and 159 (93%)
      had viral load less than 40 copies/ml. Mean duration of illness and mean duration
      of treatment were 77 (+/-42.7) and 68 (+/-41) months, respectively. Of all
      participants, 128 (62%) reported that they would consider donating either any
      organ or a specific organ/s to an HIV patient, 33 (16%) would not consider it and
      45 (22%) were unsure about donating their organs. Furthermore, 113 (55%)
      participants would consider receiving an organ from an HIV patient, 37 (18%)
      would not consider it, and 56 (27%) were unsure. Ninety-eight participants (42%)
      reported that they would consider both donating and receiving an organ.
      Multinomial logistic regression analysis found that significantly more Black
      African than Caucasian participants were unsure about organ donation (p = 0.011,
      OR = 3.887). Participants with longer duration of infection were significantly
      less likely to consider receiving an organ from an HIV patient (p = 0.036, OR =
      1.297). Overall, the study findings indicated that the majority of participants
      were in favour of organ transplant between HIV patients. Use of HIV-infected
      donors could potentially reduce current organ waiting list among HIV patients.

PMID- 25614523
TI  - Incident syphilis infection among people who inject drugs in Tijuana, Mexico.
AB  - Given that syphilis is associated with HIV infection among people who inject
      drugs (PWID), we examined syphilis incidence among PWID in Tijuana, Mexico. From
      2006 to 2007, 940 PWID (142 women and 798 men) were recruited via respondent
      driven sampling and followed for 18 months. At semi-annual visits, participants
      were tested for syphilis and completed surveys, which collected information on
      socio-demographics, sexual behaviours, substance use and injection behaviours.
      Poisson regression was used to estimate syphilis incidence rates (IRs), incidence
      rate ratios (IRRs) and 95% confidence intervals (CIs). Twenty-one participants
      acquired syphilis during follow-up (IR = 1.57 per 100 person-years, 95% CI: 1.02
      2.41). In a multivariate analysis, syphilis incidence was higher among women (IRR
      = 3.90, 95% CI: 1.37-11.09), HIV-positive participants (IRR = 4.60, 95% CI: 1.58
      13.39) and those who reported ever exchanging sex for drugs, money, or other
      goods (IRR = 2.74, 95% CI: 0.97-7.76), while syphilis incidence was lower among
      those living in Tijuana for a longer duration (IRR = 0.95 per year, 95% CI: 0.91
      1.00) and those reporting at least daily injection drug use (past 6 months) (IRR
      = 0.22, 95% CI: 0.09-0.54). Our findings suggest interventions that address the
      destabilising conditions associated with migration and integrate sexual and drug
      related risk reduction strategies may help reduce syphilis incidence among PWID
      along the Mexico-US border.

PMID- 25614526
TI  - Development of an aggregated system for classifying causes of drug-related
      problems.
AB  - BACKGROUND: More than 20 different types of classification systems for drug
      related problems (DRPs) and their causes have been developed. Classification is
      necessary to describe and assess clinical, organizational, and economic impacts
      of DRPs through documentation of collected data. However, many researchers have
      judged classification systems incomplete when describing their data, and have
      modified them or developed their own. This variability between systems has made
      study comparisons difficult. OBJECTIVES: To perform a category-by-category
      comparison of the content of selected DRP classification systems to construct an
      aggregated cause-of-DRP classification system containing the content of all
      systems. METHOD: DRP classification systems were identified after a literature
      review, with 7 chosen based on their use in varied health care settings,
      geographical diversity, frequency of use, and method of development. These
      systems were critically analyzed, and the content of each category was compared
      and aggregated where appropriate. A hierarchy of categories was constructed to
      include all content from all systems. Any modifications that previous studies may
      have made to the 7 systems were also cross-referenced to ensure that no concepts
      were missing from the newly aggregated system. Clinical examples to optimize
      application, and instructions for when or when not to use categories, were
      developed. Interrater agreement for classification of the causes of DRPs from 10
      medication reviews was performed between 3 clinical pharmacists and the authors'
      gold standard. RESULTS: We found variation in developmental methods, category
      descriptions, number and types of categories, and validation methods between the
      7 selected systems, together with intermingling of categories identified as
      causes of DRPs with DRPs themselves. A hierarchical classification system was
      constructed consisting of 9 cause-of-DRP categories, 33 subcategories, and 58 sub
      subcategories, for which interrater agreements were 82.5%, 74.6%, and 58.8%,
      respectively. CONCLUSION: An aggregated classification system was constructed
      through a unique and transparent developmental process that may provide the most
      comprehensive description of causes of DRPs to date. This may facilitate teaching
      of pharmaceutical care, comparisons of clinical practice, and measurement of the
      effectiveness of pharmaceutical care interventions.

PMID- 25614525
TI  - Subunit disassembly and inhibition of TNFalpha by a semi-synthetic bicyclic
      peptide.
AB  - Macrocyclic peptides are potentially a source of powerful drugs, but their de
      novo discovery remains challenging. Here we describe the discovery of a high
      affinity (Kd = 10 nM) peptide macrocycle (M21) against human tumor necrosis
      factor-alpha (hTNFalpha), a key drug target in the treatment of inflammatory
      disorders, directly from diverse semi-synthetic phage peptide repertoires. The
      bicyclic peptide M21 (ACPPCLWQVLC) comprises two loops covalently anchored to a
      2,4,6-trimethyl-mesitylene core and upon binding induces disassembly of the
      trimeric TNFalpha cytokine into dimers and monomers. A 2.9 A crystal structure of
      the M21/hTNFalpha complex reveals the peptide bound to a hTNFalpha dimer at a
      normally buried epitope in the trimer interface overlapping the binding site of a
      previously discovered small molecule ligand (SPD304), which also induces TNF
      trimer dissociation and synergizes with M21 in the inhibition of TNFalpha
      cytotoxicity. The discovery of M21 underlines the potential of semi-synthetic
      bicyclic peptides as ligands for the discovery of cryptic epitopes, some of which
      are poorly accessible to antibodies. 

PMID- 25614527
TI  - Safety and efficacy of target-specific anticoagulants in patients with venous
      thromboembolism.
AB  - OBJECTIVE: To review the role of target-specific anticoagulants (TSACs) for the
      treatment of venous thromboembolism (VTE) and their associated efficacy and
      safety. DATA SOURCES: Peer-reviewed clinical trials, review articles, and
      relevant treatment guidelines were identified from MEDLINE (1966 to November
      2014) using the following search terms: venous thromboembolism, vitamin K
      antagonist (VKA), target-specific anticoagulant, deep-vein thrombosis, pulmonary
      embolism. Results were limited to human trials published in English. Citations
      from articles were reviewed for additional references. STUDY SELECTION AND DATA
      EXTRACTION: Clinical trials evaluating VTE treatment were included. Trials that
      evaluated alternative end points were excluded. DATA SYNTHESIS: Patients with VTE
      have a high risk of developing recurrent events and subsequent death if not
      treated in an appropriate manner. TSACs have been evaluated in several large
      clinical trials in patients with acute VTE. These trials have shown positive
      outcomes when compared with VKAs for treatment of VTE in the general population.
      Paralleled with these results, TSACs had similar or lower rates of bleeding
      compared with VKAs. CONCLUSIONS: Taken together, available evidence suggests that
      TSACs produce similar clinical benefits with less bleeding incidence when
      compared with VKAs in the treatment of VTE. There are significant differences
      between each study investigating this class of medication for VTE treatment. Each
      TSAC has potential advantages, and to date, there has been no head-to-head trial
      comparing them.

PMID- 25614528
TI  - Implementing extended-infusion cefepime as standard of care in a children's
      hospital: a prospective descriptive study.
AB  - BACKGROUND: Extended-infusion cefepime (EIC) has been associated with decreased
      mortality in adults, but to our knowledge, there are no studies in children.
      OBJECTIVE: The objective of this study was to determine the feasibility of
      implementing EIC as the standard dosing strategy in a pediatric population.
      METHODS: This was a descriptive study of children aged 1 month to 17 years,
      including patients in the intensive care unit, who received cefepime after
      admission to a freestanding, tertiary care children's hospital. Patients were
      excluded if they were admitted to the neonatal intensive care unit or received
      cefepime in the outpatient, operating, or emergency department areas. Demographic
      and clinical data for patients who received cefepime from April through August
      2013, the period following EIC implementation, were extracted from the medical
      records. RESULTS: A total of 150 patients were included in the study, with a
      median age (interquartile range [IQR]) of 6 years (2-12.3 years) and median
      weight (IQR) of 20.7 kg (13.2-42.8 kg); 143 patients received cefepime via
      extended infusions, and 10 (7.0%) of those were changed to a 30-minute infusion
      during treatment. The most common reasons for infusion time change were
      intravenous (IV) incompatibility and IV access concerns, responsible for 50% of
      changes. Dosing errors and reported incidents during therapy were sparse (n = 12,
      8.0%) and were most commonly related to renal dosing errors and/or initial dose
      error by prescriber. CONCLUSIONS: Because 93.0% of the patients who initially
      received EIC remained on EIC, implementation of EIC as the standard dosing
      strategy was feasible in this pediatric hospital.

PMID- 25614529
TI  - A novel behavioral intervention in adolescents with type 1 diabetes mellitus
      improves glycemic control: preliminary results from a pilot randomized control
      trial.
AB  - PURPOSE: The purpose of this study was to develop and pilot-test an innovative
      behavioral intervention in adolescents with type 1 diabetes mellitus (T1DM)
      incorporating structured care of a pet to improve glycemic control. METHODS:
      Twenty-eight adolescents with A1C > 8.5% (69 mmol/mol) were randomly assigned to
      either the intervention group (care of a Betta splendens pet fish) or the control
      group (usual care). Adolescents in the intervention group were given instructions
      to associate daily and weekly fish care duties with diabetes self-management
      tasks, including blood glucose testing and parent-adolescent communication.
      RESULTS: After 3 months, the participants in the intervention group exhibited a
      statistically significant decrease in A1C level (-0.5%) compared with their peers
      in the control group, who had an increase in A1C level (0.8%) (P = .04). The
      younger adolescents (10-13 years of age) demonstrated a greater response to the
      intervention, which was statistically significant (-1.5% vs 0.6%, P = .04),
      compared with the older adolescents (14-17 years of age). CONCLUSIONS: Structured
      care of a pet fish can improve glycemic control in adolescents with T1DM, likely
      by providing cues to perform diabetes self-management behaviors.

PMID- 25614530
TI  - Lithium treatment and risk for dementia in adults with bipolar disorder:
      population-based cohort study.
AB  - BackgroundLithium inhibits glycogen synthase kinase-3, an enzyme implicated in
      the pathogenesis of dementia.AimsTo examine the association of lithium and
      dementia risk in a large claims-based US cohort of publicly insured older adults
      with bipolar disorder.MethodThe cohort included individuals >=50 years diagnosed
      with bipolar disorder who did not receive dementia-related services during the
      prior year. Each follow-up day was classified by past-year cumulative duration of
      lithium use (0, 1-60, 61-300 and 301-365 days). Dementia diagnosis was the study
      outcome. Anticonvulsants commonly used as mood stabilisers served as a negative
      control.ResultsCompared with non-use, 301-365 days of lithium exposure was
      associated with significantly reduced dementia risk (hazard ratio (HR) = 0.77,
      95% CI 0.60-0.99). No corresponding association was observed for shorter lithium
      exposures (HR = 1.04, 95% CI 0.83-1.31 for 61-300 days; HR = 1.07, 95% CI 0.67
      1.71 for 1-60 days) or for any exposure to anticonvulsants.ConclusionsContinuous
      lithium treatment may reduce dementia risk in older adults with bipolar disorder.

PMID- 25614531
TI  - The ACCESS study: Zelen randomised controlled trial of a package of care for
      people presenting to hospital after self-harm.
AB  - BACKGROUND: The problem of people presenting to hospitals with self-harm is
      important because such presentations are common, there is a clear link to suicide
      and a high premature mortality. However, the best treatment for this population
      is unclear. AIMS: To see whether a package of measures, that included regular
      postcards and problem-solving therapy, improved outcomes at 1 year compared with
      usual care in people who presented to hospital with self-harm (the ACCESS study:
      trial registration Australian and New Zealand Clinical Trials Registry
      ACTRN12609000641291). METHOD: The design of the study was a Zelen randomised
      controlled trial. The primary outcome was re-presentation to hospital with self
      harm within 12 months of the index episode. RESULTS: There were no significant
      differences in the primary outcome and most of the secondary outcomes between the
      two groups. About half the people offered problem-solving therapy did not receive
      it, for various reasons. CONCLUSIONS: The package as offered had little effect on
      the proportion of people re-presenting to hospital with self-harm. The dose of
      problem-solving therapy may have been too small to have an effect and there was a
      difficulty engaging participants in active treatment.

PMID- 25614532
TI  - Adverse childhood events and psychosis in bipolar affective disorder.
AB  - BACKGROUND: There has been increasing interest in the association between
      childhood trauma and psychosis. Proposals for potential mechanisms involved
      include affective dysregulation and cognitive appraisals of threat. AIMS: To
      establish if, within bipolar disorder, childhood events show a significant
      association with psychosis, and in particular with symptoms driven by
      dysregulation of mood or with a persecutory content. METHOD: Data on lifetime
      ever presence of psychotic symptoms were determined by detailed structured
      interview with case-note review (n = 2019). Childhood events were recorded using
      a self-report questionnaire and case-note information. RESULTS: There was no
      relationship between childhood events, or childhood abuse, and psychosis per se.
      Childhood events were not associated with an increased risk of persecutory or
      other delusions. Significant associations were found between childhood abuse and
      auditory hallucinations, strongest between sexual abuse and mood congruent or
      abusive voices. These relationships remain significant even after controlling for
      lifetime-ever cannabis misuse. CONCLUSIONS: Within affective disorder, the
      relationship between childhood events and psychosis appears to be relatively
      symptom-specific. It is possible that the pathways leading to psychotic symptoms
      differ, with delusions and non-hallucinatory symptoms being influenced less by
      childhood or early environmental experience.

PMID- 25614533
TI  - Factors associated with inconsistency in self-reported mild traumatic brain
      injury over time among military personnel in Iraq.
AB  - BACKGROUND: Estimates of the prevalence of mild traumatic brain injury (mTBI)
      among military personnel and combat veterans rely almost exclusively on
      retrospective self-reports; however, reliability of these reports has received
      little attention. AIMS: To examine the consistency of reporting of mTBI over time
      and identify factors associated with inconsistent reporting. METHOD: A
      longitudinal cohort of 948 US National Guard Soldiers deployed to Iraq completed
      self-report questionnaire screening for mTBI and psychological symptoms while in
      theatre 1 month before returning home (time 1, T1) and 1 year later (time 2, T2).
      RESULTS: Most respondents (n = 811, 85.5%) were consistent in their reporting of
      mTBI across time. Among those who were inconsistent in their reports (n = 137,
      14.5%), the majority denied mTBI at T1 and affirmed mTBI at T2 (n = 123, 89.8%).
      Respondents rarely endorsed mTBI in-theatre and later denied mTBI (n = 14, 10.2%
      of those with inconsistent reports). Post-deployment post-traumatic stress
      symptoms and non-specific physical complaints were significantly associated with
      inconsistent report of mTBI. CONCLUSIONS: Military service members' self-reports
      of mTBI are generally consistent over time; however, inconsistency in
      retrospective self-reporting of mTBI status is associated with current post
      traumatic stress symptoms and non-specific physical health complaints.

PMID- 25614534
TI  - Adrenal insufficiency from over-the-counter medicine as a cause of shock in rural
      area of Thailand: a study at Sisaket Provincial Hospital during October 2012-
      October 2013.
AB  - This retrospective study was carried out to estimate the prevalence of an adrenal
      crisis at a provincial hospital in Thailand over a period of 1 year, and also to
      explore the relationship between adrenal insufficiency and over-the-counter
      medicine (OTCM) ingestion. We recruited those patients admitted at Sisaket
      Hospital between October 2012 and October 2013 who were diagnosed with shock and
      adrenal insufficiency or adrenal crisis. Of 2,435 patients diagnosed with shock
      from all causes, 62 (2.55 %) were diagnosed with adrenal crisis, of whom 31
      (50.0%) gave a history of OTCM ingestion. This study suggests adrenal crisis with
      shock is not that uncommon and that the use of OTCM may be the prime culprit. 

PMID- 25614535
TI  - Venom ophthalmia from Naja mossambica in KwaZulu Natal, South Africa: a reminder
      to all that for ocular chemical injury, dilution is the solution.
AB  - Venom ophthalmia caused by venoms of spitting elapids such as the Mozambique
      Spitting Cobra (Naja mossambica) is seen in regions where people live in close
      proximity to elapids, such as in the KwaZulu Natal region of South Africa. We
      report such a case in a 43-year-old woman who presented to Mosvold Hospital, a
      district hospital in South Africa. Clinical features and best practice management
      of venom ophthalmia will be discussed. 

PMID- 25614536
TI  - Clinician-friendly lower extremity physical performance tests in athletes: a
      systematic review of measurement properties and correlation with injury. Part 2-
      the tests for the hip, thigh, foot and ankle including the star excursion balance
      test.
AB  - OBJECTIVE: To review the quality of literature and measurement properties of
      physical performance tests (PPTs) of the lower extremity in athletes. METHODS:
      Using the PICOS method we established our research question as to whether
      individual PPTs of the lower extremity have any relationship to injury in
      competitive athletes ages 12 years to adult (no limit). A search strategy was
      constructed by combining the terms 'lower extremity' and synonyms for
      'performance test' and names of performance tests with variants of the term
      'athlete'. After examining the knee in part 1 of this 2 part series, the current
      report focuses on findings in the rest of the lower extremity. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were
      followed and the Consensus-based Standards for the selection of health
      Measurement Instruments (COSMIN) checklist was used to critique the
      methodological quality of each paper. A second measure was used to analyse the
      quality of the measurement properties of each test. RESULTS: Thirty-one articles
      examined the measurement properties of 14 PPTs pertaining to the lower extremity.
      The terminology used to name and describe the tests and methodology by which the
      tests were conducted was inconsistent. The star excursion balance test performed
      in three directions (anterior, posteromedial, and posterolateral) appears to be
      the only test to be associated with increased injury risk. There is moderate
      evidence that the one leg hop for distance and the hexagon hop can distinguish
      between normal and unstable ankles. There is also moderate evidence that the
      medial hop can distinguish between painful and normal hips in dancers.
      CONCLUSIONS: Currently, there is relatively limited research-backed information
      on PPTs of the lower extremity in athletes. We would suggest convening an
      international consortium comprised of experts in sports to standardise the
      descriptions and methodologies, and to set forth a research agenda to establish
      definitively the measurement properties of the most common PPTs.

PMID- 25614537
TI  - Protecting the health of the @hlete: how online technology may aid our common
      goal to prevent injury and illness in sport.
AB  - Online technology dominates our era and eHealth has become a reality for sports
      clinicians and researchers. Contemporary online platforms enable self-monitoring
      and provide tailored feedback to the different stakeholders who play a role in
      the health and care of athletes. Innovations such as digital monitoring, mobile
      applications and connected hardware provide the critical tools to solve current
      enigmas in sports medicine research, and to streamline and facilitate injury
      prevention, management and rehabilitation. eHealth is not an emerging future of
      sports medicine-the technology to move our field forward in terms of research and
      practice is already available. This Analysis is based on Evert Verhagen's keynote
      presentation at the IOC World Conference on Injury and Illness Prevention in
      Sport (Monaco, 12 April 2014). It outlines the use of eHealth in research,
      implementation and practice, and provides an overview of possibilities and
      opportunities that existing and emerging eHealth solutions provide for sports and
      exercise medicine and physiotherapy. 

PMID- 25614539
TI  - BVA seeks a clear timetable for OV tendering announcement.

PMID- 25614540
TI  - L3 million grant to tackle anthelmintic resistance.

PMID- 25614541
TI  - Dairy producers need greater certainty about their future, says EFRACom.

PMID- 25614542
TI  - Listed status for Battersea's first cattery.

PMID- 25614543
TI  - Putting a value on horses.

PMID- 25614544
TI  - Progress and challenges in controlling neglected zoonotic diseases.
AB  - Suzanne Jarvis reports from the Fourth International Meeting on the Control of
      Neglected Zoonotic Diseases, hosted by the World Health Organization in Geneva in
      November. The meeting looked at progress that has been made in controlling these
      diseases and at what the next steps should be for further control.

PMID- 25614545
TI  - Support for Glasgow community project.

PMID- 25614546
TI  - What is acceptable?

PMID- 25614547
TI  - 'Salamander plague' on Britain's doorstep.
AB  - Chytridiomycosis can cause mass declines in amphibians, and the chytrid fungus
      Batrachochytrium dendrobatidis is the classic cause of this disease. However,
      recently, a second strain of chytrid fungus has emerged in Europe, resulting in
      major declines in fire salamanders. The Zoological Society of London (ZSL)
      discussed this, and the implications for the UK, at a meeting in December in
      London. Georgina Mills reports.

PMID- 25614548
TI  - Parasitic gastroenteritis in lambs widespread.
AB  - Parasitic gastroenteritis diagnosed in lambs by all veterinary investigation
      centres, Clostridium perfringens epsilon enterotoxaemia suspected in two cows,
      Comparative quarterly porcine reproductive and respiratory syndrome diagnoses
      reach a 10-year peak, Failure of an entire colony of gulls in Cumbria,
      Endoparasitism the predominant feature in exotic farmed animals, These are among
      matters discussed in the Animal and Plant Health Agency's (APHA's) disease
      surveillance report for September 2014.

PMID- 25614549
TI  - Scrapie: a particularly persistent pathogen.

PMID- 25614550
TI  - Dr yes or Dr no?

PMID- 25614551
TI  - Retained and persistent deciduous teeth in cats.

PMID- 25614552
TI  - Veterinary practice marketeer.
AB  - Justin Phillips is marketing manager at White Cross Vets and the Veterinary
      Marketing Association's (VMA's) Young Veterinary Marketeer of the Year. Here, he
      describes what he does and why he believes other practices should embrace
      marketing to improve their quality and client care. 

PMID- 25614553
TI  - Diary of a poultry intern.
AB  - Christmas is a demanding time for vets working in the poultry industry. As the
      memory of the season fades, William Garton reflects on his initial four months as
      a poultry intern. 

PMID- 25614557
TI  - Draft Genome Sequences of Symbiotic and Nonsymbiotic Rhizopus microsporus Strains
      CBS 344.29 and ATCC 62417.
AB  - Specific Rhizopus microsporus pathovars harbor bacterial endosymbionts
      (Burkholderia rhizoxinica) for the production of a phytotoxin. Here, we present
      the draft genome sequences of two R. microsporus strains, one symbiotic (ATCC
      62417), and one endosymbiont-free (CBS 344.29). The gene predictions were
      supported by RNA sequencing (RNA-seq) data. The functional annotation sets the
      basis for comparative analyses. 

PMID- 25614558
TI  - Draft Genome Sequence of Marine Bacterium Streptomyces sp. Strain CNQ431, a
      Producer of the Cytokine Inhibitor Splenocin.
AB  - Currently, corticosteroids are the most potent anti-inflammatory drugs on the
      market. Here, we announce the draft genome sequence of the marine-derived
      Streptomyces sp. strain CNQ431, which produces cytokine inhibitors, termed
      splenocins, which display potent suppression of cytokine production at a
      comparable level to that of corticosteroids. The genome is approximately 498,750
      bp with 72.03% G+C content. 

PMID- 25614559
TI  - Complete genome sequence of classical Swine Fever virus subgenogroup 2.1 from
      assam, India.
AB  - We report the complete genome sequence of a classical swine fever virus
      (genogroup 2.1), isolated from an outbreak in Assam, India. This particular
      isolate showed a high degree of genetic variation within the subgenogroup 2.1 and
      may serve as a potential reference strain of the 2.1 genogroup of classical swine
      fever virus (CSFV) in the Indian subcontinent. 

PMID- 25614560
TI  - Draft Genome Sequence and Gene Annotation of the Entomopathogenic Fungus
      Verticillium hemipterigenum.
AB  - Verticillium hemipterigenum (anamorph Torrubiella hemipterigena) is an
      entomopathogenic fungus and produces a broad range of secondary metabolites.
      Here, we present the draft genome sequence of the fungus, including gene
      structure and functional annotation. Genes were predicted incorporating RNA-Seq
      data and functionally annotated to provide the basis for further genome studies. 

PMID- 25614561
TI  - Genome Sequences of the Listeria ivanovii subsp. ivanovii Type Strain and Two
      Listeria ivanovii subsp. londoniensis Strains.
AB  - We present the complete genomes of Listeria ivanovii subsp. ivanovii WSLC 3010
      (ATCC 19119(T)), Listeria ivanovii subsp. londoniensis WSLC 30151 (SLCC 8854),
      and Listeria ivanovii subsp. londoniensis WSLC 30167 (SLCC 6032), representing
      the type strain of the species and two strains of the same serovar but different
      properties, respectively. 

PMID- 25614562
TI  - Complete Genome Sequence of Anaeromyxobacter sp. Fw109-5, an Anaerobic, Metal
      Reducing Bacterium Isolated from a Contaminated Subsurface Environment.
AB  - We report the genome sequence of Anaeromyxobacter sp. Fw109-5, isolated from
      nitrate- and uranium-contaminated subsurface sediment of the Oak Ridge Integrated
      Field-Scale Subsurface Research Challenge (IFC) site, Oak Ridge Reservation, TN.
      The bacterium's genome sequence will elucidate its physiological potential in
      subsurface sediments undergoing in situ uranium bioremediation and natural
      attenuation. 

PMID- 25614563
TI  - Complete Genome Sequence of Ehrlichia mineirensis, a Novel Organism Closely
      Related to Ehrlichia canis with a New Host Association.
AB  - We report here the complete genome sequencing of Ehrlichia mineirensis, an
      Ehrlichia organism that was isolated from the hemolymph of Rhipicephalus
      microplus-engorged females. E. mineirensis is the best characterized Ehrlichia
      isolate from a novel cattle-related clade closely related to the monocytotropic
      pathogen E. canis. 

PMID- 25614564
TI  - Draft Genome Sequence of Alkaliphilic Exiguobacterium sp. Strain HUD, Isolated
      from a Polymicrobial Consortia.
AB  - An alkaliphilic microorganism from the genus Exiguobacterium, Exiguobacterium sp.
      strain HUD was isolated from a fermentative, methanogenic polymicrobial microcosm
      operating at pH 10. The draft genome shows the presence of genes encoding for the
      metabolism of a range of carbohydrates under both aerobic and anaerobic
      conditions. 

PMID- 25614565
TI  - Complete Genome Sequence of Bacillus pumilus Strain WP8, an Efficient Plant
      Growth-Promoting Rhizobacterium.
AB  - Bacillus pumilus strain WP8 is an efficient plant growth-promoting
      rhizobacterium. Here, we present the complete genome of WP8 and its genes
      involved in plant growth promotion and biocontrol. 

PMID- 25614566
TI  - Correction for Lopez-Perez et al., Genome Sequence of "Thalassospira australica"
      NP3b2T Isolated from St. Kilda Beach, Tasman Sea.

PMID- 25614567
TI  - Draft Genome Sequence of Cryophilic Basidiomycetous Yeast Mrakia blollopis SK-4,
      Isolated from an Algal Mat of Naga-ike Lake in the Skarvsnes Ice-Free Area, East
      Antarctica.
AB  - Mrakia blollopis strain SK-4 was isolated from an algal mat of Naga-ike, a lake
      in Skarvsnes, East Antarctica. Here, we report the draft genome sequence of M.
      blollopis SK-4. This is the first report on the genome sequence of any cold
      adapted fungal species. 

PMID- 25614568
TI  - Full-Length Genome Sequence of Type M/emm83 Group A Streptococcus pyogenes Strain
      STAB1101, Isolated from Clustered Cases in Brittany.
AB  - Here, we announce the complete annotated genome sequence of a Streptococcus
      pyogenes M/emm83 strain, STAB1101, isolated from clustered cases in homeless
      persons in Brittany (France). The genome is composed of 1,709,790 bp, with a G+C
      content of 38.4% and 1,550 identified coding sequences (CDS), and it harbors a
      Tn916-like transposon. 

PMID- 25614569
TI  - Draft Genome Sequence of Enterobacter sp. Strain UCD-UG_FMILLET (Phylum
      Proteobacteria).
AB  - Here, we present the draft genome of Enterobacter sp. strain UCD-UG_FMILLET. This
      strain is an endophyte isolated from the roots of finger millet, an Afro-Indian
      cereal crop. The genome contains 4,801,411 bp in 53 scaffolds. 

PMID- 25614570
TI  - Draft Genome Sequence of Burkholderia gladioli Strain UCD-UG_CHAPALOTE (Phylum
      Proteobacteria).
AB  - Here, we present the draft genome of Burkholderia gladioli strain UCD
      UG_CHAPALOTE. This strain is an endophyte isolated from surface sterilized seeds
      of an ancient Mexican landrace of corn, Chapalote. The genome contains 8,527,129
      bp in 109 scaffolds. 

PMID- 25614571
TI  - Draft Genome Sequence of Bacillus selenatarsenatis SF-1T, a Promising Agent for
      Bioremediation of Environments Contaminated with Selenium and Arsenic.
AB  - Bacillus selenatarsenatis sp. nov. strain SF-1(T) is a promising agent for
      bioremediation of environments contaminated with selenium and arsenic. Here, we
      report the draft genome sequence of this strain. 

PMID- 25614572
TI  - Complete and Assembled Genome Sequence of Bifidobacterium kashiwanohense PV20-2,
      Isolated from the Feces of an Anemic Kenyan Infant.
AB  - The complete genome sequence of Bifidobacterium kashiwanohense strain PV20-2, an
      infant feces isolate, was determined using single-molecule real-time sequencing
      (SMRT). Hierarchical genome assembly resulted in a completely assembled genome of
      2,370,978 bp. The B. kashiwanohense PV20-2 genome is the first completely
      sequenced and assembled genome of the species. 

PMID- 25614573
TI  - Bifidobacterium pseudolongum Strain PV8-2, Isolated from a Stool Sample of an
      Anemic Kenyan Infant.
AB  - The complete genome sequence of Bifidobacterium pseudolongum PV8-2, isolated from
      feces of an anemic Kenyan infant, was determined using single-molecule real-time
      (SMRT) technology. The genome consists of a 2-Mbp chromosome and a 4-kb plasmid. 

PMID- 25614574
TI  - Draft genome sequence of calothrix strain 336/3, a novel h2-producing
      cyanobacterium isolated from a finnish lake.
AB  - We announce the draft genome sequence of Calothrix strain 336/3, an N2-fixing
      heterocystous filamentous cyanobacterium isolated from a natural habitat.
      Calothrix 336/3 produces higher levels of hydrogen than Nostoc punctiforme PCC
      73102 and Anabaena strain PCC 7120 and, therefore, is of interest for potential
      technological applications. 

PMID- 25614575
TI  - Draft Genome Sequence of Rhodovulum sp. Strain NI22, a Naphthalene-Degrading
      Marine Bacterium.
AB  - Rhodovulum sp. strain NI22 is a hydrocarbon-degrading member of the genus
      Rhodovulum. The draft genome of Rhodovulum sp. NI22 is 3.8 Mb in size, with 3,756
      coding sequences and 64.4% G+C content. The catechol and gentisate pathways for
      naphthalene degradation are predicted to be present in Rhodovulum sp. NI22. 

PMID- 25614576
TI  - Complete Genome Sequence of Sphingobacterium sp. Strain ML3W, Isolated from Wings
      of Myotis lucifugus Infected with White Nose Syndrome.
AB  - Sphingobacterium sp. strain ML3W was isolated from the wing of a bat infected
      with white nose syndrome. We report the complete 5.33-Mb genome sequence of
      Sphingobacterium sp. strain ML3W, obtained using Pacific Biosciences technology.
      Being the second complete Sphingobacterium sequence, this will increase knowledge
      of the genus. 

PMID- 25614577
TI  - Draft Genome Sequence of Spirochaeta sp. Strain JC202, an Endosymbiont of the
      Termite (Isoptera) Gut.
AB  - We announce here the draft genome sequence of Spirochaeta sp. strain JC202
      isolated from gut of a termite (Isoptera). The genome suggests that Spirochaeta
      sp. JC202 has the capability for natural conjugation with the help of fimbriae
      and pili. Experimental evidence and the genome sequence suggest that strain JC202
      is capable of producing colicin V and a bacteriocin group of peptides in a
      specific interaction. 

PMID- 25614578
TI  - Erratum for Sarker et al., Molecular Characterization of Genome Sequences of Beak
      and Feather Disease Virus from the Australian Twenty-Eight Parrot (Barnardius
      zonarius semitorquatus).

PMID- 25614579
TI  - Assessment of phytochemicals, antioxidant, and anti-inflammatory potential of
      Boerhavia procumbens Banks ex Roxb.
AB  - Boerhavia procumbens is traditionally used in the treatment of various disorders
      including jaundice and gonorrhea, is a refrigerant, and exhibits anti
      inflammatory and antispasmodic activities. The purpose of this study was to
      determine the phytochemical classes, antioxidant and anti-inflammatory activities
      of methanol extract (BPME) and different fractions (n-hexane (BPHE), ethyl
      acetate (BPEE), n-butanol (BPBE), and residual aqueous fraction (BPAE)) of B.
      procumbens against carrageenan-induced paw edema in rats. To assess the anti
      inflammatory effects of B. procumbens, 42 Sprague Dawley male rats (150-200 g)
      were randomly divided into seven groups. Group I received distilled water and
      group II was treated with diclofenac potassium (10 mg/kg) body weight (bw)
      orally. Groups III, IV, V, VI, and VII were administered BPME, BPHE, BPEE, BPBE,
      and BPAE (200 mg/kg bw) orally, 1 h before the treatment with carrageenan (10
      mg/kg bw) in rats. Anti-inflammatory effects of B. procumbens were determined by
      estimating the inhibition of edema at 1st, 2nd, and 3rd hour after carrageenan
      injection. Qualitative analysis of methanol extract indicated the composition of
      diverse classes, namely, flavonoids, tannins, saponins, phlobatannins, cardiac
      glycosides, alkaloids, terpenoids, and anthraquinones. Quantitative determination
      illustrated that BPBE and BPEE possessed the highest concentration of total
      phenolic (60.45 +/- 2.1 mg gallic acid equivalent per gram sample) and total
      flavonoid content (68.05 +/- 2.3 mg rutin equivalent per gram sample),
      respectively. A dose-dependent response for antioxidant activity was exhibited by
      all the samples. The sample with the highest aptitude for antioxidant activity
      was the BPBE for 2,2-azobis,3-ethylbenzothiozoline-6-sulfonic acid radical
      scavenging and total antioxidant capacity. Carrageenan-induced paw edema was
      significantly (p < 0.05) inhibited by BPBE and BPME at the 1st, 2nd, and 3rd hour
      and was comparable to control drug diclofenac potassium. Results revealed that
      various fractions of B. procumbens manifested the antioxidant and anti
      inflammatory potential and accredit the local use of B. procumbens in various
      disorders.

PMID- 25614580
TI  - Dibutyl phthalate induces oxidative stress and impairs spermatogenesis in adult
      rats.
AB  - Phthalates are abundantly produced plasticizers, and dibutyl phthalate (DBP) is
      the most widely used derivative in various consumer products and medical devices.
      This study was conducted to further explore the potential testicular toxicity of
      DBP in adult rats and to elucidate the underlying mechanisms. Adult male albino
      rats were treated orally with DBP at doses of 0, 200, 400, or 600 mg/kg/day for
      15 consecutive days. Testicular weight, sperm count, and motility were
      significantly decreased. Treatment with DBP decreased serum follicle-stimulating
      hormone and testosterone levels and testicular lactate dehydrogenase activity.
      DBP treatment also decreased serum total antioxidant capacity and the activities
      of the testicular antioxidant enzymes, such as superoxide dismutase, catalase,
      and glutathione reductase. Further, DBP treatment provoked degeneration with
      absence of spermatogenesis and sperms and necrosis in some of seminiferous
      tubules. These results indicated that oxidative stress and subsequent decrease in
      testosterone secretion were the potential underlying mechanism of DBP-induced
      testicular toxicity.

PMID- 25614581
TI  - In vitro activation of dibromoacetonitrile to cyanide by myeloperoxidase.
AB  - Dibromoacetonitrile (DBAN) is a disinfection by-product classified as a potential
      human and animal carcinogen. This study aimed at investigating the ability of
      myeloperoxidase (MPO) to oxidize DBAN to cyanide (CN-) in vitro Detection of CN-
      served as a marker for the possible generation of free radical intermediates
      implicated in DBAN-induced toxicity. Optimum conditions for the oxidation of DBAN
      to CN- were characterized with respect to pH, temperature, and time of incubation
      as well as DBAN, MPO, potassium chloride, and hydrogen peroxide (H2O2)
      concentrations in incubation mixtures. Maximum reaction velocity and Michaelis
      Menten constant were assessed. Addition of sodium hypochlorite to the reaction
      mixtures significantly enhanced the rate of the reaction. Addition of the MPO
      inhibitors, sodium azide, 4-amino benzoic acid hydrazine, or indomethacin to the
      reaction mixtures significantly decreased the rate of DBAN oxidation. Inclusion
      of the antioxidant enzyme superoxide dismutase in the incubation mixtures
      significantly decreased the rate of reaction. Inclusion of the sulfhydryl
      compounds as reduced glutathione, N-acetylcysteine, d-penicillamine, or l
      cysteine enhanced the rate of DBAN oxidation. These results demonstrate the
      ability of MPO/H2O2/chloride ion system to oxidize DBAN to CN- and provide
      insight for the elucidation of DBAN chronic toxicity.

PMID- 25614582
TI  - Protective effects of grape seed extract on cadmium-induced testicular damage,
      apoptosis, and endothelial nitric oxide synthases expression in rats.
AB  - This study aims to evaluate the protective effect of grape seed proanthocyanidin
      extract (GSPE) on cadmium (Cd)-induced testicular apoptosis, endothelial nitric
      oxide synthases (eNOS) expression, and toxicity in rats. A total of 24 male
      Wistar rats were divided into four groups, namely, control, Cd (2.5 mg/kg), Cd +
      GSPE (100 mg/kg/day), and GSPE. Spermatogenesis and mean seminiferous tubule
      diameter were significantly decreased in the Cd groups. Furthermore, the GSPE
      treated animals showed an improved histological appearance in the Cd group. The
      immunoreactivity of eNOS and the number of apoptotic cells were increased in Cd
      group. Our data indicate a significant reduction of terminal deoxynucleotide
      transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling staining
      and a decrease in the expression of eNOS in the testes tissue of the Cd group
      treated with GSPE therapy. Therefore, our results suggest that GSPE acts as a
      potent protective agent against Cd-induced testicular toxicity in rats.

PMID- 25614584
TI  - Identification of conformational neutralization sites on the fusion protein of
      mumps virus.
AB  - In spite of the success of the mumps vaccination, recent mumps outbreaks have
      been reported even among individuals with a history of mumps vaccination. For a
      better understanding of why the vaccination failed in cases of vaccinees who fell
      ill during recent mumps outbreaks, the immunological events during infection
      and/or vaccination should be better defined. In the work presented here we sought
      to identify new neutralization sites on the mumps virus surface glycoproteins. By
      using anti-mumps mAbs, three amino acid positions at residues 221, 323 and 373 in
      the F protein of mumps virus were shown to be located in at least two
      conformational neutralization epitopes. mAbs that specifically target these sites
      effectively neutralized mumps virus in vitro. The newly acquired glycosylation
      site at position 373 or loss of the existing one at position 323 was identified
      as the mechanism behind the escape from the specific mAbs. Based on the findings
      of this study, we suggest that the influence of the antigenic structure of the F
      protein should not be ignored in a thorough investigation of the underlying
      mechanism of the mumps vaccine failure or when making a strategy for development
      of a new vaccine.

PMID- 25614583
TI  - Muscle cell fate choice requires the T-box transcription factor midline in
      Drosophila.
AB  - Drosophila Midline (Mid) is an ortholog of vertebrate Tbx20, which plays roles in
      the developing heart, migrating cranial motor neurons, and endothelial cells. Mid
      functions in cell-fate specification and differentiation of tissues that include
      the ectoderm, cardioblasts, neuroblasts, and egg chambers; however, a role in the
      somatic musculature has not been described. We identified mid in genetic and
      molecular screens for factors contributing to somatic muscle morphogenesis. Mid
      is expressed in founder cells (FCs) for several muscle fibers, and functions
      cooperatively with the T-box protein H15 in lateral oblique muscle 1 and the
      segment border muscle. Mid is particularly important for the specification and
      development of the lateral transverse (LT) muscles LT3 and LT4, which arise by
      asymmetric division of a single muscle progenitor. Mid is expressed in this
      progenitor and its two sibling FCs, but is maintained only in the LT4 FC. Both
      muscles were frequently missing in mid mutant embryos, and LT4-associated
      expression of the transcription factor Kruppel (Kr) was lost. When present, LT4
      adopted an LT3-like morphology. Coordinately, mid misexpression caused LT3 to
      adopt an LT4-like morphology and was associated with ectopic Kr expression. From
      these data, we concluded that mid functions first in the progenitor to direct
      development of LT3 and LT4, and later in the FCs to influence whichever of these
      differentiation profiles is selected. Mid is the first T-box factor shown to
      influence LT3 and LT4 muscle identity and, along with the T-box protein Optomotor
      blind-related-gene 1 (Org-1), is representative of a new class of transcription
      factors in muscle specification. 

PMID- 25614585
TI  - Last 20 aa of the West Nile virus NS1' protein are responsible for its retention
      in cells and the formation of unique heat-stable dimers.
AB  - West Nile virus (WNV), a mosquito-borne flavivirus, is the major cause of
      arboviral encephalitis in the USA. As with other members of the Japanese
      encephalitis virus serogroup, WNV produces an additional non-structural protein,
      NS1', a C-terminal extended product of NS1 generated as the result of a -1
      programmed ribosomal frameshift (PRF). We have previously shown that mutations
      abolishing the PRF, and consequently NS1', resulted in reduced neuroinvasiveness.
      However, whether this was caused by the PRF event itself or by the lack of a PRF
      product, NS1', or a combination of both, remains undetermined. Here, we showed
      that WNV NS1' formed a unique subpopulation of heat- and low-pH-stable dimers. C
      terminal truncations and mutational analysis employing an NS1'-expressing plasmid
      showed that stability of NS1' dimers was linked to the penultimate 10 aa. To
      examine the role of NS1' heat-stable dimers in virus replication and
      pathogenicity, a stop codon mutation was introduced into NS1' to create a WNV
      producing a truncated version of NS1' lacking the last 20 aa, but not affecting
      the PRF. NS1' protein produced by this mutant virus was secreted more efficiently
      than WT NS1', indicating that the sequence of the last 20 aa of NS1' was
      responsible for its cellular retention. Further analysis of this mutant showed
      growth kinetics in cells and virulence in weanling mice after peripheral
      infection similar to the WT WNVKUN, suggesting that full-length NS1' was not
      essential for virus replication in vitro and for virulence in mice.

PMID- 25614586
TI  - Genetic diversity in three bovine-like human G8P[14] and G10P[14] rotaviruses
      suggests independent interspecies transmission events.
AB  - The group A rotavirus (RVA) P[14] genotype has been detected sporadically in
      humans and is thought to be acquired through zoonotic transmission. The present
      study describes the full-length genome analysis of two G8P[14] and one G10P[14]
      human RVAs detected in Italy. The strains possessed the typical bovine-like I2-R2
      C2-M2-A3/A11-N2-T6-E2-H3 genotype constellation. All the segments of the two
      G8P[14] RVAs were most closely related to bovine(-like) strains but were
      relatively distant to each other, suggesting two independent interspecies
      transmission events. Likewise, the G10P[14] RVA gene segments were most similar
      to bovine(-like) RVAs but distinct from the G8 strains. The history of these
      strains probably involved the interspecies transmission of these viruses to
      humans from an as-yet-unidentified animal host, without evidence of reassortment
      events involving human RVAs. These results reinforce the potential of animal
      viruses to cross the host-species barrier, causing disease and increased viral
      genetic diversity in humans.

PMID- 25614587
TI  - Prediction and characterization of novel epitopes of serotype A foot-and-mouth
      disease viruses circulating in East Africa using site-directed mutagenesis.
AB  - Epitopes on the surface of the foot-and-mouth disease virus (FMDV) capsid have
      been identified by monoclonal antibody (mAb) escape mutant studies leading to the
      designation of four antigenic sites in serotype A FMDV. Previous work focused on
      viruses isolated mainly from Asia, Europe and Latin America. In this study we
      report on the prediction of epitopes in African serotype A FMDVs and testing of
      selected epitopes using reverse genetics. Twenty-four capsid amino acid residues
      were predicted to be of antigenic significance by analysing the capsid sequences
      (n = 56) using in silico methods, and six residues by correlating capsid sequence
      with serum-virus neutralization data. The predicted residues were distributed on
      the surface-exposed capsid regions, VP1-VP3. The significance of residue changes
      at eight of the predicted epitopes was tested by site-directed mutagenesis using
      a cDNA clone resulting in the generation of 12 mutant viruses involving seven
      sites. The effect of the amino acid substitutions on the antigenic nature of the
      virus was assessed by virus neutralization (VN) test. Mutations at four different
      positions, namely VP1-43, VP1-45, VP2-191 and VP3-132, led to significant
      reduction in VN titre (P value = 0.05, 0.05, 0.001 and 0.05, respectively). This
      is the first time, to our knowledge, that the antigenic regions encompassing
      amino acids VP1-43 to -45 (equivalent to antigenic site 3 in serotype O), VP2-191
      and VP3-132 have been predicted as epitopes and evaluated serologically for
      serotype A FMDVs. This identifies novel capsid epitopes of recently circulating
      serotype A FMDVs in East Africa.

PMID- 25614590
TI  - The neonatal Fc receptor does not modulate hepatitis C virus neutralization.
AB  - The neonatal Fc receptor (FcRn) is the only receptor known to be able to
      transport IgG across cell barriers and may therefore modulate virus infection.
      FcRn is expressed efficiently in hepatocytes. We therefore investigated the
      possible involvement of an FcRn-dependent mechanism in hepatitis C virus (HCV)
      neutralization. Our study, in both HCV pseudoparticles and HCV in cell-culture
      models, showed that FcRn was not involved in the intracellular neutralization of
      HCV, in contrast to the situation observed for influenza A virus. 

PMID- 25614589
TI  - Escherichia coli and Staphylococcus phages: effect of translation initiation
      efficiency on differential codon adaptation mediated by virulent and temperate
      lifestyles.
AB  - Rapid biosynthesis is key to the success of bacteria and viruses. Highly
      expressed genes in bacteria exhibit a strong codon bias corresponding to the
      differential availability of tRNAs. However, a large clade of lambdoid coliphages
      exhibits relatively poor codon adaptation to the host translation machinery, in
      contrast to other coliphages that exhibit strong codon adaptation to the host.
      Three possible explanations were previously proposed but dismissed: (1) the phage
      borne tRNA genes that reduce the dependence of phage translation on host tRNAs,
      (2) lack of time needed for evolving codon adaptation due to recent host
      switching, and (3) strong strand asymmetry with biased mutation disrupting codon
      adaptation. Here, we examined the possibility that phages with relatively poor
      codon adaptation have poor translation initiation which would weaken the
      selection on codon adaptation. We measured translation initiation by: (1) the
      strength and position of the Shine-Dalgarno (SD) sequence, and (2) the stability
      of the secondary structure of sequences flanking the SD and start codon known to
      affect accessibility of the SD sequence and start codon. Phage genes with strong
      codon adaptation had significantly stronger SD sequences than those with poor
      codon adaptation. The former also had significantly weaker secondary structure in
      sequences flanking the SD sequence and start codon than the latter. Thus,
      lambdoid phages do not exhibit strong codon adaptation because they have
      relatively inefficient translation initiation and would benefit little from
      increased elongation efficiency. We also provided evidence suggesting that phage
      lifestyle (virulent versus temperate) affected selection intensity on the
      efficiency of translation initiation and elongation.

PMID- 25614588
TI  - Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza
      virus and lyssaviruses.
AB  - IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks
      cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways.
      In humans and mice, IFITM3 limits influenza-induced morbidity and mortality.
      Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as
      antiviral restriction factors in mammalian species other than humans and mice is
      unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus
      scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino
      acid residues known to be important for IFITM3 function were conserved in the pig
      and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co
      localized with transferrin (early endosomes) and CD63 (late
      endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry
      mediated by multiple influenza haemagglutinin subtypes and lyssavirus
      glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced
      influenza virus yields and nucleoprotein expression. Conversely, small
      interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells
      enhanced virus replication, demonstrating that these genes are functional in
      their species of origin at endogenous levels. In summary, we showed that IFITMs
      function as potent broad-spectrum antiviral effectors in two mammals - pigs and
      bats - identified as major reservoirs for emerging viruses.

PMID- 25614591
TI  - New enveloped dsRNA phage from freshwater habitat.
AB  - Cystoviridae is a family of bacteriophages with a tri-segmented dsRNA genome
      enclosed in a tri-layered virion structure. Here, we present a new putative
      member of the Cystoviridae family, bacteriophage phiNN. phiNN was isolated from a
      Finnish lake in contrast to the previously identified cystoviruses, which
      originate from various legume samples collected in the USA. The nucleotide
      sequence of the virus reveals a strong genetic similarity (~80 % for the L
      segments, ~55 % for the M-segments and ~84 % for the S-segments) to Pseudomonas
      phage phi6, the type member of the virus family. However, the relationship
      between phiNN and other cystoviruses is more distant. In general, proteins
      located in the internal parts of the virion were more conserved than those
      exposed on the virion surface, a phenomenon previously reported among eukaryotic
      dsRNA viruses. Structural models of several putative phiNN proteins propose that
      cystoviral structures are highly conserved.

PMID- 25614592
TI  - Pregnancy serum facilitates hepatitis E virus replication in vitro.
AB  - Hepatitis E virus (HEV) infection causes high mortality in pregnant women.
      However, the pathogenic mechanisms of HEV infection in pregnant women remain
      unknown. In this study, the roles of pregnancy serum in HEV infection were
      investigated using an efficient cell culture system. HEV infection was
      exacerbated by supplementing with pregnancy serum, especially theat in third
      trimester of pregnancy. Oestrogen receptors (ER-alpha and ER-beta) were activated
      in cells supplemented with pregnancy serum and were significantly inhibited
      during HEV infection. Type I IFN, especially IFN-beta, showed delayed
      upregulation in HEV-infected cells supplemented with the serum in the third
      trimester of pregnancy, which indicated that delayed IFN-beta expression may
      facilitate viral replication. Results suggested that pregnancy serum accelerated
      HEV replication by suppressing oestrogen receptors and type I IFN in the early
      stage of infection.

PMID- 25614594
TI  - The N-N non-covalent domain of the nucleocapsid protein of type 2 porcine
      reproductive and respiratory syndrome virus enhances induction of IL-10
      expression.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) usually establishes a
      prolonged infection and causes an immunosuppressive state. It has been proposed
      that IL-10 plays an important role in PRRSV-induced immunosuppression. However,
      this mechanism has not been completely elucidated. In this study, we found that
      transfection of 3D4/2 macrophages with the N protein gene of type 2 PRRSV
      significantly upregulated IL-10 expression at the transcriptional level.
      Moreover, alanine substitution mutation analysis revealed that the N protein
      residues 33-37, 65-68 and 112-123 were related to the upregulation of IL-10
      promoter activity. Recombinant PRRSV with mutations at residues 33-37 in the N
      protein (rQ33-5A and rS36A) recovered from corresponding infectious cDNA clones
      and induced significantly lower levels of IL-10 production in infected monocyte
      derived dendritic cells, as compared with their revertants rQ33-5A(R) and
      rS36A(R), and the wild-type recombinant PRRSV strain rNT/wt. These data indicate
      that the type 2 PRRSV N protein plays an important role in IL-10 induction and
      the N-N non-covalent domain is associated with this activity. 

PMID- 25614593
TI  - Genetic characterization of human coxsackievirus A6 variants associated with
      atypical hand, foot and mouth disease: a potential role of recombination in
      emergence and pathogenicity.
AB  - Human coxsackievirus A6 (CVA6) is an enterically transmitted enterovirus. Until
      recently, CVA6 infections were considered as being of minor clinical
      significance, and only rarely aetiologically linked with hand, foot and mouth
      disease (HFMD) associated with other species A enteroviruses (particularly EV71
      and CVA16). From 2008 onwards, however, CVA6 infections have been associated with
      several outbreaks worldwide of atypical HFMD (aHFMD) accompanied by a
      varicelliform rash. We recently reported CVA6-associated eczema herpeticum
      occurring predominantly in children and young adults in Edinburgh in January and
      February 2014. To investigate genetic determinants of novel clinical phenotypes
      of CVA6, we genetically characterized and analysed CVA6 variants associated with
      eczema herpeticum in Edinburgh in 2014 and those with aHFMD in CAV isolates
      collected from 2008. A total of eight recombinant forms (RFs) have circulated
      worldwide over the past 10 years, with the particularly recent appearance of RF-H
      associated with eczema herpeticum cases in Edinburgh in 2014. Comparison of
      phylogenies and divergence of complete genome sequences of CVA6 identified
      recombination breakpoints in 2A-2C, within VP3, and between 5' untranslated
      region and VP1. A Bayesian temporal reconstruction of CVA6 evolution since 2004
      provided estimates of dates and the actual recombination events that generated
      more recently appearing recombination groups (RF-E, -F, -G and -H). Associations
      were observed between recombination groups and clinical presentations of
      herpangina, aHFMD and eczema herpeticum, but not with VP1 or other structural
      genes. These observations provided evidence that NS gene regions may potentially
      contribute to clinical phenotypes and outcomes of CVA6 infection.

PMID- 25614595
TI  - Submental negative pressure application decreases collapsibility of the passive
      pharyngeal airway in nonobese women.
AB  - The pharyngeal airway is surrounded by soft tissues that are also enclosed by
      bony structures such as the mandible, maxilla, and cervical spine. The passive
      pharyngeal airway is therefore structurally analogous to a collapsible tube
      within a rigid box. Cross-sectional area of the tube is determined by transmural
      pressure, the pressure difference between intraluminal and extraluminal
      pressures. Due to a lack of knowledge on the influence of extraluminal soft
      tissue pressure on the human pharyngeal airway patency, we hypothesized that
      application of negative external pressure to the submental region decreases
      collapsibility of the passive pharynx, and that obese individuals have less
      response to the intervention than nonobese individuals. Static mechanical
      properties of the passive pharynx were compared before and during application of
      submental negative pressure in 10 obese and 10 nonobese adult women under general
      anesthesia and paralysis. Negative pressure was applied through use of a silicone
      collar covering the entire submental region and a vacuum pump. In nonobese
      subjects, application of submental negative pressure (-25 and -50 cmH2O)
      significantly decreased closing pressures at the retropalatal airway by 2.3 +/-
      3.2 cmH2O and 2.0 +/- 3.0 cmH2O, respectively, and at the retroglossal airway by
      2.9 +/- 2.7 cmH2O and 3.7 +/- 2.6 cmH2O, respectively, and the intervention
      stiffened the retroglossal pharyngeal airway wall. No significant mechanical
      changes were observed during application of submental negative pressure in obese
      subjects. Conclusively, application of submental negative pressure was found to
      decreases collapsibility of the passive pharyngeal airway in nonobese Japanese
      women. 

PMID- 25614596
TI  - Single-fiber expression and fiber-specific adaptability to short-term intense
      exercise training of Na+-K+-ATPase alpha- and beta-isoforms in human skeletal
      muscle.
AB  - The Na(+)-K(+)-ATPase (NKA) plays a key role in muscle excitability, but little
      is known in human skeletal muscle about fiber-type-specific differences in NKA
      isoform expression or adaptability. A vastus lateralis muscle biopsy was taken in
      17 healthy young adults to contrast NKA isoform protein relative abundance
      between type I and IIa fibers. We further investigated muscle fiber-type-specific
      NKA adaptability in eight of these adults following 4-wk repeated-sprint exercise
      (RSE) training, comprising three sets of 5 * 4-s sprints, 3 days/wk. Single
      fibers were separated, and myosin heavy chain (I and IIa) and NKA (alpha1-3 and
      beta1-3) isoform abundance were determined via Western blotting. All six NKA
      isoforms were expressed in both type I and IIa fibers. No differences between
      fiber types were found for alpha1-, alpha2-, alpha3-, beta1-, or beta3-isoform
      abundances. The NKA beta2-isoform was 27% more abundant in type IIa than type I
      fibers (P < 0.05), with no other fiber-type-specific trends evident. RSE training
      increased beta1 in type IIa fibers (pretraining 0.70 +/- 0.25, posttraining 0.84
      +/- 0.24 arbitrary units, 42%, P < 0.05). No training effects were found for
      other NKA isoforms. Thus human skeletal muscle expresses all six NKA isoforms and
      not in a fiber-type-specific manner; this points to their different functional
      roles in skeletal muscle cells. Detection of elevated NKA beta1 after RSE
      training demonstrates the sensitivity of the single-fiber Western blotting
      technique for fiber-type-specific intervention effects. 

PMID- 25614597
TI  - Effect of breath holding on cerebrovascular hemodynamics in normal pregnancy and
      preeclampsia.
AB  - Preeclampsia (PE) is associated with endothelial dysfunction and impaired
      autonomic function, which is hypothesized to cause cerebral hemodynamic
      abnormalities. Our aim was to test this hypothesis by estimating the difference
      in the cerebrovascular response to breath holding (BH; known to cause sympathetic
      stimulation) between women with preeclampsia and a group of normotensive
      controls. In a prospective cohort analysis, cerebral blood flow velocity (CBFV)
      in the middle cerebral artery (transcranial Doppler), blood pressure (BP,
      noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were
      simultaneously recorded during a 20-s breath hold maneuver. CBFV changes were
      broken down into standardized subcomponents describing the relative contributions
      of BP, cerebrovascular resistance index (CVRi), critical closing pressure (CrCP),
      and resistance area product (RAP). The area under the curve (AUC) was calculated
      for changes in relation to baseline values. A total of 25 preeclamptic (before
      treatment) and 25 normotensive women in the second half of pregnancy were
      enrolled, and, 21 patients in each group were included in the analysis. The
      increase in CBFV and EtCO2 was similar in both groups. However, the AUC for CVRi
      and RAP during BH was significantly different between the groups (3.05 +/- 2.97
      vs. -0.82 +/- 4.98, P = 0.006 and 2.01 +/- 4.49 vs. -2.02 +/- 7.20, P = 0.037),
      indicating an early, transient increase in CVRi and RAP in the control group,
      which was absent in PE. BP had an equal contribution in both groups. Women with
      preeclampsia have an altered initial CVRi response to the BH maneuver. We propose
      that this is due to blunted sympathetic or myogenic cerebrovascular response in
      women with preeclampsia. 

PMID- 25614598
TI  - Independent effects of endurance training and weight loss on peak fat oxidation
      in moderately overweight men: a randomized controlled trial.
AB  - Endurance training increases peak fat oxidation (PFO) during exercise, but
      whether this is independent of changes in body weight is not known. The aim of
      the present study was to investigate the effects of endurance training with or
      without weight loss or a diet-induced weight loss on PFO and on key skeletal
      muscle mitochondrial proteins involved in fat oxidation. Sixty moderately
      overweight, sedentary but otherwise healthy men were randomized to 12 wk of
      training (T), diet (D), training and increased caloric intake (T-iD), or
      continuous sedentary control (C). Isoenergetic deficits corresponding to 600
      kcal/day were comprised of endurance exercise for T and caloric restriction for
      D. T-iD completed similar training but was not in 600 kcal deficit because of
      dietary replacement. PFO and the exercise intensity at which this occurred
      (FatMax) were measured by a submaximal exercise test and calculated by polynomial
      regression. As intended by study design, a similar weight loss was observed in T
      (-5.9 +/- 0.7 kg) and D (-5.2 +/- 0.8 kg), whereas T-iD (-1.0 +/- 0.5 kg) and C
      (0.1 +/- 0.6 kg) remained weight stable. PFO increased to a similar extent with
      42% in T [0.16 g/min; 95% confidence intervals (CI): 0.02; 0.30, P = 0.02] and
      41% in T-iD (0.16 g/min; 95% CI: 0.01; 0.30, P = 0.04) compared with C, but did
      not increase in D (P = 0.96). In addition, the analysis of covariance showed that
      changes in both PFO (0.10 g/min; 95% CI: 0.03; 0.17, P = 0.03) and FatMax (6.3%
      Vo2max; 95% CI: 1.4; 11.3, P < 0.01) were independently explained by endurance
      training. In conclusion, endurance training per se increases PFO in moderately
      overweight men. 

PMID- 25614599
TI  - Ultrasound reveals negligible cocontraction during isometric plantar flexion and
      dorsiflexion despite the presence of antagonist electromyographic activity.
AB  - Because of the approximate linear relationship between muscle force and muscle
      activity, muscle forces are often estimated during maximal voluntary isometric
      contractions (MVICs) from torque and surface electromyography (sEMG)
      measurements. However, sEMG recordings from a target muscle may contain cross
      talk originating from nearby muscles, which could lead to erroneous force
      estimates. Here we used ultrasound imaging to measure in vivo muscle fascicle
      length (Lf) changes and sEMG to measure muscle activity of the tibialis anterior,
      medial gastrocnemius, lateral gastrocnemius, and soleus muscles during ramp MVICs
      in plantar and dorsiflexion directions (n = 8). After correcting longitudinal Lf
      changes for ankle rotation, the antagonist Lf at peak antagonist root-mean-square
      (RMS) amplitude were significantly longer than the agonist Lf at this sEMG
      matched level. On average, Lf shortened from resting length by 1.29 to 2.90 mm
      when muscles acted as agonists and lengthened from resting length by 0.43 to 1.16
      mm when muscles acted as antagonists (depending on the muscle of interest). The
      lack of fascicle shortening when muscles acted as antagonists indicates that
      cocontraction was likely to be negligible, despite cocontraction as determined by
      sEMG of between 7 and 23% MVIC across all muscles. Different interelectrode
      distances (IEDs) over the plantar flexors revealed significantly higher
      antagonist RMS amplitudes for the 4-cm IEDs compared with the 2-cm IEDs, which
      further indicates that cross-talk was present. Consequently, investigators should
      be wary about performing agonist torque corrections for isometric plantar flexion
      and dorsiflexion based on the antagonist sEMG trace and predicted antagonist
      moment. 

PMID- 25614600
TI  - Peripheral chemoreceptor control of cardiovascular function at rest and during
      exercise in heart failure patients.
AB  - Peripheral chemoreceptor activity/sensitivity is enhanced in chronic heart
      failure (HF), and sensitivity is linked to greater mortality. This study aimed to
      determine the role of the peripheral chemoreceptor in cardiovascular control at
      rest and during exercise in HF patients and controls. Clinically stable HF
      patients (n = 11; ejection fraction: 39 +/- 5%) and risk-matched controls (n =
      10; ejection fraction: 65 +/- 2%) performed randomized trials with or without
      dopamine infusion (2 MUg.min(-1).kg(-1)) at rest and during 40% maximal voluntary
      contraction handgrip (HG) exercise, and a resting trial of 2 min of inspired 100%
      oxygen. Both dopamine and hyperoxia were used to inhibit the peripheral
      chemoreceptor. At rest in HF patients, dopamine decreased ventilation (P = 0.02),
      decreased total peripheral resistance index (P = 0.003), and increased cardiac
      and stroke indexes (P <= 0.01), yet there was no effect of dopamine on these
      variables in controls (P >= 0.7). Hyperoxia lowered ventilation in HF (P = 0.01),
      but not in controls (P = 0.9), indicating suppression of the peripheral
      chemoreceptors in HF. However, no decrease of total peripheral resistance index
      was observed in HF. As expected, HG increased heart rate, ventilation, and
      brachial conductance of the nonexercising arm in controls and HF patients. During
      dopamine infusion, there were no changes in mean arterial pressure, heart rate,
      or ventilation responses to HG in either group (P >= 0.26); however, brachial
      conductance increased with dopamine in the control group (P = 0.004), but
      decreased in HF (P = 0.02). Our findings indicate that the peripheral
      chemoreceptor contributes to cardiovascular control at rest in HF patients and
      during exercise in risk-matched controls. 

PMID- 25614601
TI  - Localization and stretch-dependence of lung elastase activity in development and
      compensatory growth.
AB  - Synthesis and remodeling of the lung matrix is necessary for primary and
      compensatory lung growth. Because cyclic negative force is applied to developing
      lung tissue during the respiratory cycle, we hypothesized that stretch is a
      critical regulator of lung matrix remodeling. By using quantitative image
      analysis of whole-lung and whole-lobe elastin in situ zymography images, we
      demonstrated that elastase activity increased twofold during the alveolar stage
      of postnatal lung morphogenesis in the mouse. Remodeling was restricted to
      alveolar walls and ducts and was nearly absent in dense elastin band structures.
      In the mouse pneumonectomy model of compensatory lung growth, elastase activity
      increased threefold, peaking at 14 days postpneumonectomy and was higher in the
      accessory lobe compared with other lobes. Remodeling during normal development
      and during compensatory lung growth was different with increased major airway and
      pulmonary arterial remodeling during development but not regeneration, and with
      homogenous remodeling throughout the parenchyma during development, but increased
      remodeling only in subpleural regions during compensatory lung growth. Left lung
      wax plombage prevented increased lung elastin during compensatory lung growth. To
      test whether the adult lung retains an innate capacity to remodel elastin, we
      developed a confocal microscope-compatible stretching device. In ex vivo adult
      mouse lung sections, lung elastase activity increased exponentially with strain
      and in peripheral regions of lung more than in central regions. Our study
      demonstrates that lung elastase activity is stretch-dependent and supports a
      model in which externally applied forces influence the composition, structure,
      and function of the matrix during periods of alveolar septation. 

PMID- 25614602
TI  - Assessment of protein synthesis in highly aerobic canine species at the onset and
      during exercise training.
AB  - Canis lupus familiaris, the domesticated dog, is capable of extreme endurance
      performance. The ability to perform sustained aerobic exercise is dependent on a
      well-developed mitochondrial reticulum. In this study we examined the cumulative
      muscle protein and DNA synthesis in groups of athletic dogs at the onset of an
      exercise training program and following a strenuous exercise training program. We
      hypothesized that both at the onset and during an exercise training program there
      would be greater mitochondrial protein synthesis rates compared with sedentary
      control with no difference in mixed or cytoplasmic protein synthesis rates.
      Protein synthetic rates of three protein fractions and DNA synthesis were
      determined over 1 wk using (2)H2O in competitive Alaskan Huskies and Labrador
      Retrievers trained for explosive device detection. Both groups of dogs had very
      high rates of skeletal muscle protein synthesis in the sedentary state [Alaskan
      Huskies: Mixed = 2.28 +/- 0.12, cytoplasmic (Cyto) = 2.91 +/- 0.10, and
      mitochondrial (Mito) = 2.62 +/- 0.07; Labrador Retrievers: Mixed = 3.88 +/- 0.37,
      Cyto = 3.85 +/- 0.06, and Mito = 2.92 +/- 0.20%/day]. Mitochondrial (Mito)
      protein synthesis rates did not increase at the onset of an exercise training
      program. Exercise-trained dogs maintained Mito protein synthesis during exercise
      training when mixed (Mixed) and cytosolic (Cyto) fractions decreased, and this
      coincided with a decrease in p-RpS6 but also a decrease in p-ACC signaling.
      Contrary to our hypothesis, canines did not have large increases in mitochondrial
      protein synthesis at the onset or during an exercise training program. However,
      dogs have a high rate of protein synthesis compared with humans that perhaps does
      not necessitate an extra increase in protein synthesis at the onset of aerobic
      exercise training. 

PMID- 25614603
TI  - Effects of caffeine and maltodextrin mouth rinsing on P300, brain imaging, and
      cognitive performance.
AB  - Caffeine (CAF) and maltodextrin (MALT) mouth rinses (MR) improve exercise
      performance. The current experiment aims to determine the effect of CAF and MALT
      MR on cognitive performance and brain activity. Ten healthy male subjects (age 27
      +/- 3 yr) completed three experimental trials. Each trial included four Stroop
      tasks: two familiarization tasks, and one task before and one task after an MR
      period. The reaction time (in milliseconds) and accuracy (percent) of simple,
      congruent, and incongruent stimuli were assessed. Electroencephalography was
      applied throughout the experiment to record brain activity. The amplitudes and
      latencies of the P300 were determined during the Stroop tasks before and after
      the MR period. Subjects received MR with CAF (0.3 g/25 ml), MALT (1.6 g/25 ml),
      or placebo (PLAC) in a randomized, double-blind, crossover design. During MR, the
      brain imaging technique standardized low-resolution brain electromagnetic
      tomography was applied. Magnitude-based inferences showed that CAF MR is likely
      trivial (63.5%) and likely beneficial (36.4%) compared with PLAC MR, and compared
      with MALT MR likely beneficial to reaction time on incongruent stimuli (61.6%).
      Additionally, both the orbitofrontal and dorsolateral prefrontal cortex were
      activated only during CAF MR, potentially explaining the likely beneficial effect
      on reaction times. MALT MR increased brain activity only within the orbitofrontal
      cortex. However, this brain activation did not alter the reaction time.
      Furthermore, no significant differences in the accuracy of stimuli responses were
      observed between conditions. In conclusion, only CAF MR exerted a likely
      beneficial effect on reaction time due to the subsequent activation of both the
      orbitofrontal and dorsolateral prefrontal cortexes. 

PMID- 25614604
TI  - Onset of asphyxial state in nonrespiring interval between cord clamping and
      ventilation increases hemodynamic lability of birth transition in preterm lambs.
AB  - Experimentally, a typical ~2-min cord clamp-to-ventilation interval in preterm
      lambs is accompanied by increased hemodynamic lability of the birth transition.
      However, whether this lability is related to development of asphyxia after cord
      clamping, or can be avoided with a shorter clamp-to-ventilation interval, is
      unknown. To address these questions, anesthetized preterm fetal lambs (gestation
      127 +/- 2 days) were instrumented with ductus arteriosus and left pulmonary
      artery flow probes to obtain right ventricular (RV) output, brachiocephalic trunk
      and aortic isthmus flow probes to measure left ventricular (LV) output, and
      aortic trunk catheters for pressure measurement and blood gas analysis. With
      hemodynamics recorded continuously, fetuses were delivered onto the ewe's abdomen
      and the cord clamped for 1.5 min before ventilation (n = 8), with aortic sampling
      at 15, 30, 45, and 60 s, or for 0.5 min, with sampling at 15 s (n = 4). With 1.5
      min cord clamping, an asphyxial state (Po2 < 10 mmHg) was evident at >=45 s, with
      bradycardia and marked falls in LV and RV outputs (by 60% and 50%, P < 0.001),
      followed after ventilation onset by tachycardia and LV and RV output surges (4-
      and 3-fold, P < 0.001). By contrast, heart rate and outputs remained stable after
      0.5-min cord clamping, with no postventilation change in heart rate or RV output,
      and a lesser rise in LV output (22%, P < 0.005). In preterm lambs, rapid
      development of an asphyxial state within 45 s in the cord clamp-to-ventilation
      interval increased hemodynamic lability of the birth transition, which was
      reduced with a shorter (~0.5 min) cord clamp-to-ventilation interval. 

PMID- 25614605
TI  - The mammalian cervical vertebrae blueprint depends on the T (brachyury) gene.
AB  - A key common feature all but three known mammalian genera is the strict seven
      cervical vertebrae blueprint, suggesting the involvement of strong conserving
      selection forces during mammalian radiation. This is further supported by reports
      indicating that children with cervical ribs die before they reach reproductive
      age. Hypotheses were put up, associating cervical ribs (homeotic transformations)
      to embryonal cancer (e.g., neuroblastoma) or ascribing the constraint in cervical
      vertebral count to the development of the mammalian diaphragm. Here, we describe
      a spontaneous mutation c.196A > G in the Bos taurus T gene (also known as
      brachyury) associated with a cervical vertebral homeotic transformation that
      violates the fundamental mammalian cervical blueprint, but does not preclude
      reproduction of the affected individual. Genome-wide mapping, haplotype tracking
      within a large pedigree, resequencing of target genome regions, and bioinformatic
      analyses unambiguously confirmed the mutant c.196G allele as causal for this
      previously unknown defect termed vertebral and spinal dysplasia (VSD) by
      providing evidence for the mutation event. The nonsynonymous VSD mutation is
      located within the highly conserved T box of the T gene, which plays a
      fundamental role in eumetazoan body organization and vertebral development. To
      our knowledge, VSD is the first unequivocally approved spontaneous mutation
      decreasing cervical vertebrae number in a large mammal. The spontaneous VSD
      mutation in the bovine T gene is the first in vivo evidence for the hypothesis
      that the T protein is directly involved in the maintenance of the mammalian seven
      cervical vertebra blueprint. It therefore furthers our knowledge of the T-protein
      function and early mammalian notochord development. 

PMID- 25614606
TI  - Locally epistatic genomic relationship matrices for genomic association and
      prediction.
AB  - In plant and animal breeding studies a distinction is made between the genetic
      value (additive plus epistatic genetic effects) and the breeding value (additive
      genetic effects) of an individual since it is expected that some of the epistatic
      genetic effects will be lost due to recombination. In this article, we argue that
      the breeder can take advantage of the epistatic marker effects in regions of low
      recombination. The models introduced here aim to estimate local epistatic line
      heritability by using genetic map information and combining local additive and
      epistatic effects. To this end, we have used semiparametric mixed models with
      multiple local genomic relationship matrices with hierarchical designs. Elastic
      net postprocessing was used to introduce sparsity. Our models produce good
      predictive performance along with useful explanatory information. 

PMID- 25614607
TI  - A systems-level approach to parental genomic imprinting: the imprinted gene
      network includes extracellular matrix genes and regulates cell cycle exit and
      differentiation.
AB  - Genomic imprinting is an epigenetic mechanism that restrains the expression of ~
      100 eutherian genes in a parent-of-origin-specific manner. The reason for this
      selective targeting of genes with seemingly disparate molecular functions is
      unclear. In the present work, we show that imprinted genes are coexpressed in a
      network that is regulated at the transition from proliferation to quiescence and
      differentiation during fibroblast cell cycle withdrawal, adipogenesis in vitro,
      and muscle regeneration in vivo. Imprinted gene regulation is not linked to
      alteration of DNA methylation or to perturbation of monoallelic, parent-of-origin
      dependent expression. Overexpression and knockdown of imprinted gene expression
      alters the sensitivity of preadipocytes to contact inhibition and adipogenic
      differentiation. In silico and in cellulo experiments showed that the imprinted
      gene network includes biallelically expressed, nonimprinted genes. These control
      the extracellular matrix composition, cell adhesion, cell junction, and
      extracellular matrix-activated and growth factor-activated signaling. These
      observations show that imprinted genes share a common biological process that may
      account for their seemingly diverse roles in embryonic development, obesity,
      diabetes, muscle physiology, and neoplasm.

PMID- 25614608
TI  - Voices of Alzheimer Caregivers on Positive Aspects of Caregiving.
AB  - PURPOSE: To discover positive gains as constructed by family caregivers of
      relatives with Alzheimer's disease. DESIGN AND METHODS: Fifty-seven Hong Kong
      Chinese primary caregivers provided 669 diary recordings over an 8-week period,
      describing daily events and experiences in which positive gains were achieved.
      The diaries were analyzed independently by two researchers using thematic
      analysis. RESULTS: Ten themes related to positive gains were identified: (a)
      insights about dementia and acceptance of the condition, (b) a sense of purpose
      and commitment to the caregiving role, (c) feelings of gratification when the
      care-recipient (CR) was functioning relatively well, (d) mastering skills to
      handle the CR, (e) increased patience and tolerance, (f) cultivating positive
      meanings and humor amidst difficult circumstances, (g) letting go of things, such
      as when the CR's qualities had been lost or personal agenda had become
      unrealistic, (h) developing a closer relationship with the CR, (i) finding
      support, and (j) feeling useful helping other caregivers. IMPLICATIONS: In
      addition to treating negative outcomes such as depression, practitioners and
      researchers should, identify means to promote positive gains. Strategies
      mentioned in the caregivers' diaries, such as reframing stressful situations in a
      more positive light, may provide input into the design of such interventions.

PMID- 25614609
TI  - A Typology of New Residents' Adjustment to Continuing Care Retirement
      Communities.
AB  - PURPOSE OF THE STUDY: The study was designed to examine the diverse experiences
      of older adults upon their transition to continuing care retirement communities
      (CCRCs). DESIGN AND METHODS: As part of a larger qualitative study on CCRC
      residents and their adult children, the first wave of interviews with 59 CCRC
      residents located in 12 different CCRCs was analyzed. A line-by-line analysis was
      followed by constant comparisons within each interview and across interviews in
      order to identify commonalities and differences. Subsequent to the identification
      of major thematic categories, whole interviews were analyzed to identify unique
      response-patterns across interviews. FINDINGS: Three major themes emerged: (a)
      continuity versus discontinuity in life experiences following the transition to
      the CCRC; (b) time-orientation (e.g., past, present, or future); and (c) place
      attachment (e.g., within the CCRC or in the larger community). These 3 themes
      distinguished among four different types of CCRC residents: "shades of gray,"
      "still searching after all these years," "disapprover," and "I finally found it."
      IMPLICATIONS: The study offers a unique perspective on the adjustment process to
      CCRCs, by stressing the need to view qualitative differences in adjustment,
      rather than level of adjustment. Whereas CCRCs allow a segment of older adults to
      truly enjoy the opportunity for a new beginning in old age, for others, the
      transition does not pose a major change from past life experiences and is not
      viewed with the same level of enthusiasm.

PMID- 25614610
TI  - Leptomeningeal dissemination from an ethmoidal sinus adenocarcinoma in
      cerebrospinal fluid cytology.

PMID- 25614611
TI  - Chronic obstructive pulmonary disease and allied conditions is a strong
      independent risk factor for osteoporosis and pathologic fractures: a population
      based cohort study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease and allied conditions (COPD) is
      frequently associated with various comorbidities. This study examined the
      association between osteoporosis and pathologic fractures in a sample of patients
      with COPD. METHODS: In this cohort study, claims data from the National Health
      Insurance Research Database of Taiwan were used to evaluate the risk between COPD
      and osteoporosis. Using data from the Longitudinal Health Insurance Database
      2000, we conducted a retrospective cohort study by investigating patients aged 20
      years and older who were newly diagnosed with COPD and comparing them with
      controls without COPD during 2000-2010. In addition, we used univariable and
      multivariable Cox proportional hazards regression models to measure the
      association between COPD and the risk of osteoporosis. RESULTS: Our results
      revealed that COPD was significantly associated with a high risk of osteoporosis,
      regardless of whether the patients with COPD were corticosteroid users and
      irrespective of age and sex. After adjustment for covariates, the COPD patients
      exhibited a 1.54-fold higher risk of developing osteoporosis (hazard ratio 1.54,
      95% confidence interval 1.44-1.64). COPD was a stronger risk factor for
      osteoporosis in men. Moreover, patients with severe COPD had a higher risk of
      osteoporosis or pathologic fractures. CONCLUSION: This study revealed that COPD,
      which shares the characteristics of inflammatory diseases, is associated with a
      higher risk of osteoporosis after adjustment for comorbidities.

PMID- 25614612
TI  - Big lips.

PMID- 25614613
TI  - The role of biologics in treatment of connective tissue disease-associated
      interstitial lung disease.
AB  - With an increased understanding of the molecular pathways of inflammation and
      autoimmunity, the development of targeted biological agents has revolutionized
      the management of connective tissue diseases (CTDs). There has been an explosion
      in the development of these drugs in the last decade, targeting diseases in
      diverse fields including: allergic disorders, oncology, neuroinflammatory
      disorders, inflammatory bowel disease, macular degeneration and CTDs. In this
      last field, commonly applied biologics fall into two categories: cytokine
      inhibitors and lymphocyte-targeted therapies. The former group includes the
      antitumour necrosis factor alpha (TNF-alpha), anti-interleukin (IL)-6 receptor
      monoclonal antibodies and IL-1 receptor antagonists, whilst the latter
      encompasses the anti-CD20, B-cell depleting, monoclonal antibody (mAb), Rituximab
      and the anti-T-cell activation agent, Abatacept. This review will examine our
      developing experience in the use of these agents in the treatment of CTD-related
      interstitial lung diseases, with a particular focus on B-cell depletion. 

PMID- 25614614
TI  - Mycoplasma pneumonia increases the risk of acute coronary syndrome: a nationwide
      population-based cohort study.
AB  - BACKGROUND: Studies investigating the epidemiological relationship between
      Mycoplasma pneumonia (MP) and the subsequent development of acute coronary
      syndrome (ACS) are scant. We conducted a nationwide longitudinal cohort study in
      Taiwan to explore whether MP patients are at an increased risk of developing ACS.
      METHODS: This study investigated the incidence and risk factors for ACS in 12 152
      newly diagnosed MP patients from the Taiwan National Health Insurance Research
      Database between 2004 and 2011. The control group consisted of 48 600 individuals
      without MP. The follow-up period ran from the time of initial MP diagnosis to the
      date of an ACS event, censoring, or 31 December 2011. We analyzed the risk of ACS
      by using Cox proportional hazard regression models, including variables for sex,
      age and comorbidities. RESULTS: The incidence of ACS was higher in MP patients
      than in comparison cohort (3.08 vs. 2.42 per 1000 person-years). The hazard ratio
      of developing ACS increased 37% in MP patients compared with that in the
      comparison cohort after adjustment for covariates. The effect of MP on subsequent
      ACS development appeared to 12 months after infection. CONCLUSION: This
      nationwide study determined that compared with the general population, MP
      patients exhibited a 37% increase in the risk of subsequently developing ACS.
      Clinicians should be aware of this risk in MP patients and provide appropriate
      cardiovascular management in addition to MP treatment.

PMID- 25614615
TI  - Spoke-wheel sign of focal nodular hyperplasia revealed by superb micro-vascular
      ultrasound imaging.

PMID- 25614616
TI  - Association between non-alcoholic fatty liver disease and autonomic dysfunction
      in a Chinese population.
AB  - BACKGROUND: Autonomic dysfunction (AD) accompanying with chronic liver disorders
      led to an increased risk of mortality. However, researches that investigated the
      association between non-alcoholic fatty liver disease (NAFLD) and AD were
      insufficient. AIMS: To study the association of NAFLD with AD in middle-aged and
      elderly Chinese adults. DESIGN: Four thousand nine hundred seventy-four adults
      aged 40 years or older were enrolled in this cross-sectional study. NAFLD was
      diagnosed by hepatic B-mode ultrasonography. Autonomic function was assessed
      using a simple EZSCAN test by measuring sudomotor function, with an AD index >
      50% defined as a manifestation of AD. METHODS: Pearson correlation, multiple
      stepwise linear regression, univariate and multivariate logistic regression was
      employed to examine the relationship between NAFLD and AD, controlling for
      potential confounders. RESULTS: The prevalence of AD was significantly higher in
      participants with NAFLD than those without (40.75 vs. 26.86%, P < 0.0001). Age,
      body mass index, status of diabetes, sex, diastolic blood pressure and prevalent
      NAFLD, were positively correlated with AD index in multiple stepwise linear
      regression analysis (all P < 0.05), whereas total cholesterol was negatively
      related to it (P = 0.0043). Compared with the participants without NAFLD, those
      with NAFLD had an increased odds of the prevalent AD (odds ratio 1.38; 95%
      confidence interval 1.15-1.64; P = 0.0004) after controlling for multiple
      confounders. CONCLUSIONS: The presence of NAFLD was significantly associated with
      AD, as indicated by abnormal sudomotor function. The association was independent
      from various conventional risk factors.

PMID- 25614617
TI  - Acute medicine targets: when should the clock start and 7-day consultant impact?
AB  - BACKGROUND: Early consultant review has been shown to improve outcomes in
      patients presenting to the Acute Medical Unit (AMU). The Society for Acute
      Medicine (SAM) clinical quality indicators use the time of arrival on the AMU for
      target rather than arrival in the Emergency Department (ED) although this is
      where most acute medical patients present. AIM: To determine the effect of a 7
      day Consultant Acute Physician model on patient waiting times and assess the
      impact of starting the clock for medical patients at time of ED arrival. DESIGN:
      We performed an audit at a University Hospital AMU in the North West of England.
      METHODS: Data were collected prospectively for 15 consecutive days in May-June
      2013 for all patients presenting to the AMU at University Hospital of South
      Manchester and were repeated for the same time period in 2014 following the
      introduction of a new Consultant working model. RESULTS: Four hundred and five
      patients were admitted to the AMU in the 2013 cohort compared to 456 in the 2014
      cohort. There was a significant improvement in the median waiting time for
      Consultant review from AMU admission to 5 h 53 min from 8 h 15 min (P < 0.001).
      The compliance with the SAM quality indicator for Consultant review improved from
      88.7 to 93.7% (P = 0.022). CONCLUSION: A 7-day Acute Physician working model is
      improving performance with regards to patient waiting times. We suggest that
      starting the clock for acute medical patients in the ED is a better measure of
      performance than on arrival to the AMU.

PMID- 25614618
TI  - Patient risk profiling in acute medicine: the way forward?
AB  - BACKGROUND: The identification of high-risk patients could form a basis for
      targetted intervention following an emergency medical admission. METHODS: All
      emergency admissions to our institution over 12 years (2002-13) were included. An
      Illness Severity method based on admission laboratory parameters, previously
      developed between 2002 and 2007, was investigated for the 2008-13 cohort. We
      compared the area under the receiver operating characteristic (AUROC) to predict
      a 30-day in-hospital death between the original and validating cohorts using
      logistic multiple variable analyses. We defined six risk subgroups, based on
      admission laboratory data and examined the frequency of 30-day in-hospital
      mortality within these subgroups. RESULTS: About 66 933 admissions were recorded
      in 36 271 patients. Between 2002 and 2007, the 30-day in-hospital mortality was
      11.3% but between 2008 and 2013 was 6.7% (P < 0.001). This represented an
      absolute risk reduction (ARR) of 4.6%, a relative risk reduction (RRR) of 41.0%,
      and a number needed to treat of 21.6. The laboratory model was similarly
      predictive in both cohorts-for 2002-07, the AUROC was 0.82 (95% CI 0.81, 0.82)
      and for 2008-13 was 0.82 (95% CI 0.81, 0.83). Two high-risk subgroups were
      identified within each cohort; for 2002-07, these contained 15.0 and 30.2% of
      admitted patients but 95.5% of in-hospital deaths. For 2008-13, these two groups
      contained 15.7 and 31.0% of admitted patients but 97.0% of in-hospital deaths.
      CONCLUSION: A previously described laboratory score method, based on admission
      biochemistry, identified patients at high risk for an in-hospital death. Risk
      profiling at admission is feasible for emergency medical admissions and could
      offer a means to outcome improvement.

PMID- 25614619
TI  - Changing roles of computed tomography in diagnosing acute appendicitis in
      emergency rooms.
AB  - BACKGROUND: We used the Taiwan National Health Insurance Database for analysis
      and statistics to investigate the role of computed tomography (CT) in diagnosing
      acute appendicitis. MATERIALS AND METHODS: All 10 046 patients with acute
      appendicitis were selected and categorized into two groups based on those who did
      and did not receive CT 3 days before acute appendicitis diagnosis: non-CT and CT
      groups. A noteworthy outcome was the incidence of peritonitis within 90 days
      after diagnosis of acute appendicitis. RESULTS: The rate of using CT for patients
      with acute appendicitis increased considerably from 7.9% to 52.9% from 2000 to
      2010. The peritonitis incidence rates were 3.54% and 10.7% in the non-CT and CT
      groups, respectively. Patients who received CT on the same day exhibited a 3.8
      fold higher risk of peritonitis than did those in the non-CT group. Those who
      underwent CT before diagnosis of acute appendicitis exhibited no significant
      difference of peritonitis risk when compared with those in the non-CT group. The
      CT group patients were hospitalized 2.19 days longer than the non-CT group
      patients. Patients who received CT before and on the same day were hospitalized
      1.31 and 2.43 days longer than those who did not undergo CT. CONCLUSION: Patients
      who underwent CT exhibited higher risks of peritonitis and longer hospital stays
      compared with those who did not. Moreover, patients who received CT on the same
      day of operation exhibited a higher risk of peritonitis than those who underwent
      CT 1 or 2 days before operation.

PMID- 25614620
TI  - Involvement of nephrin in human placental trophoblast syncytialization.
AB  - The placenta has numerous functions, such as transporting oxygen and nutrients
      and building the immune tolerance of the fetus. Cell fusion is an essential
      process for placental development and maturation. In human placental development,
      mononucleated cytotrophoblast (CTB) cells can fuse to form a multinucleated
      syncytiotrophoblast (STB), which is the outermost layer of the placenta. Nephrin
      is a transmembrane protein that belongs to the Ig superfamily. Previous studies
      have shown that nephrin contributes to the fusion of myoblasts into myotubes in
      zebrafish and mice, presenting a functional conservation with its Drosophila
      ortholog sticks and stones. However, whether nephrin is involved in trophoblast
      syncytialization remains unclear. In this study, we report that nephrin was
      localized predominantly in the CTB cells and STB of human placenta villi from
      first trimester to term pregnancy. Using a spontaneous fusion model of primary
      CTB cells, the expression of nephrin was found to be increased during trophoblast
      cell fusion. Moreover, the spontaneous syncytialization and the expression of
      syncytin 2, connexin 43, and human chorionic gonadotropin beta were significantly
      inhibited by nephrin-specific siRNAs. The above results demonstrate that nephrin
      plays an important role in trophoblast syncytialization. 

PMID- 25614621
TI  - Uncovering effects of antibiotics on the host and microbiota using transkingdom
      gene networks.
AB  - OBJECTIVE: Despite widespread use of antibiotics for the treatment of life
      threatening infections and for research on the role of commensal microbiota, our
      understanding of their effects on the host is still very limited. DESIGN: Using a
      popular mouse model of microbiota depletion by a cocktail of antibiotics, we
      analysed the effects of antibiotics by combining intestinal transcriptome
      together with metagenomic analysis of the gut microbiota. In order to identify
      specific microbes and microbial genes that influence the host phenotype in
      antibiotic-treated mice, we developed and applied analysis of the transkingdom
      network. RESULTS: We found that most antibiotic-induced alterations in the gut
      can be explained by three factors: depletion of the microbiota; direct effects of
      antibiotics on host tissues and the effects of remaining antibiotic-resistant
      microbes. Normal microbiota depletion mostly led to downregulation of different
      aspects of immunity. The two other factors (antibiotic direct effects on host
      tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene
      expression and amounts of active mitochondria, increasing epithelial cell death.
      By reconstructing and analysing the transkingdom network, we discovered that
      these toxic effects were mediated by virulence/quorum sensing in antibiotic
      resistant bacteria, a finding further validated using in vitro experiments.
      CONCLUSIONS: In addition to revealing mechanisms of antibiotic-induced
      alterations, this study also describes a new bioinformatics approach that
      predicts microbial components that regulate host functions and establishes a
      comprehensive resource on what, why and how antibiotics affect the gut in a
      widely used mouse model of microbiota depletion by antibiotics.

PMID- 25614622
TI  - Phosphatidylinositol 3-kinase class II alpha-isoform PI3K-C2alpha is required for
      transforming growth factor beta-induced Smad signaling in endothelial cells.
AB  - We have recently demonstrated that the PI3K class II-alpha isoform (PI3K
      C2alpha), which generates phosphatidylinositol 3-phosphate and
      phosphatidylinositol 3,4-bisphosphates, plays crucial roles in angiogenesis, by
      analyzing PI3K-C2alpha knock-out mice. The PI3K-C2alpha actions are mediated at
      least in part through its participation in the internalization of VEGF receptor-2
      and sphingosine-1-phosphate receptor S1P1 and thereby their signaling on
      endosomes. TGFbeta, which is also an essential angiogenic factor, signals via the
      serine/threonine kinase receptor complex to induce phosphorylation of Smad2 and
      Smad3 (Smad2/3). SARA (Smad anchor for receptor activation) protein, which is
      localized in early endosomes through its FYVE domain, is required for Smad2/3
      signaling. In the present study, we showed that PI3K-C2alpha knockdown nearly
      completely abolished TGFbeta1-induced phosphorylation and nuclear translocation
      of Smad2/3 in vascular endothelial cells (ECs). PI3K-C2alpha was necessary for
      TGFbeta-induced increase in phosphatidylinositol 3,4-bisphosphates in the plasma
      membrane and TGFbeta receptor internalization into the SARA-containing early
      endosomes, but not for phosphatidylinositol 3-phosphate enrichment or
      localization of SARA in the early endosomes. PI3K-C2alpha was also required for
      TGFbeta receptor-mediated formation of SARA-Smad2/3 complex. Inhibition of
      dynamin, which is required for the clathrin-dependent receptor endocytosis,
      suppressed both TGFbeta receptor internalization and Smad2/3 phosphorylation.
      TGFbeta1 stimulated Smad-dependent VEGF-A expression, VEGF receptor-mediated EC
      migration, and capillary-like tube formation, which were all abolished by either
      PI3K-C2alpha knockdown or a dynamin inhibitor. Finally, TGFbeta1-induced
      microvessel formation in Matrigel plugs was greatly attenuated in EC-specific
      PI3K-C2alpha-deleted mice. These observations indicate that PI3K-C2alpha plays
      the pivotal role in TGFbeta receptor endocytosis and thereby Smad2/3 signaling,
      participating in angiogenic actions of TGFbeta. 

PMID- 25614623
TI  - Comparisons with amyloid-beta reveal an aspartate residue that stabilizes fibrils
      of the aortic amyloid peptide medin.
AB  - Aortic medial amyloid (AMA) is the most common localized human amyloid, occurring
      in virtually all of the Caucasian population over the age of 50. The main protein
      component of AMA, medin, readily assembles into amyloid-like fibrils in vitro.
      Despite the prevalence of AMA, little is known about the self-assembly mechanism
      of medin or the molecular architecture of the fibrils. The amino acid sequence of
      medin is strikingly similar to the sequence of the Alzheimer disease (AD) amyloid
      beta (Abeta) polypeptides around the structural turn region of Abeta, where
      mutations associated with familial, early onset AD, have been identified. Asp(25)
      and Lys(30) of medin align with residues Asp(23) and Lys(28) of Abeta, which are
      known to form a stabilizing salt bridge in some fibril morphologies. Here we show
      that substituting Asp(25) of medin with asparagine (D25N) impedes assembly into
      fibrils and stabilizes non-cytotoxic oligomers. Wild-type medin, by contrast,
      aggregates into beta-sheet-rich amyloid-like fibrils within 50 h. A structural
      analysis of wild-type fibrils by solid-state NMR suggests a molecular repeat unit
      comprising at least two extended beta-strands, separated by a turn stabilized by
      a Asp(25)-Lys(30) salt bridge. We propose that Asp(25) drives the assembly of
      medin by stabilizing the fibrillar conformation of the peptide and is thus
      reminiscent of the influence of Asp(23) on the aggregation of Abeta.
      Pharmacological comparisons of wild-type medin and D25N will help to ascertain
      the pathological significance of this poorly understood protein. 

PMID- 25614624
TI  - Presenilin transmembrane domain 8 conserved AXXXAXXXG motifs are required for the
      activity of the gamma-secretase complex.
AB  - Understanding the molecular mechanisms controlling the physiological and
      pathological activity of gamma-secretase represents a challenging task in
      Alzheimer disease research. The assembly and proteolytic activity of this enzyme
      require the correct interaction of the 19 transmembrane domains (TMDs) present in
      its four subunits, including presenilin (PS1 or PS2), the gamma-secretase
      catalytic core. GXXXG and GXXXG-like motifs are critical for TMDs interactions as
      well as for protein folding and assembly. The GXXXG motifs on gamma-secretase
      subunits (e.g. APH-1) or on gamma-secretase substrates (e.g. APP) are known to be
      involved in gamma-secretase assembly and in Abeta peptide production,
      respectively. We identified on PS1 and PS2 TMD8 two highly conserved AXXXAXXXG
      motifs. The presence of a mutation causing an inherited form of Alzheimer disease
      (familial Alzheimer disease) in the PS1 motif suggested their involvement in the
      physiopathological configuration of the gamma-secretase complex. In this study,
      we targeted the role of these motifs on TMD8 of PSs, focusing on their role in PS
      assembly and catalytic activity. Each motif was mutated, and the impact on
      complex assembly, activity, and substrate docking was monitored. Different amino
      acid substitutions on the same motif resulted in opposite effects on gamma
      secretase activity, without affecting the assembly or significantly impairing the
      maturation of the complex. Our data suggest that AXXXAXXXG motifs in PS TMD8 are
      key determinants for the conformation of the mature gamma-secretase complex,
      participating in the switch between the physiological and pathological functional
      conformations of the gamma-secretase. 

PMID- 25614625
TI  - Exposure of neutralizing epitopes in the carboxyl-terminal domain of TcdB is
      altered by a proximal hypervariable region.
AB  - The sequence, activity, and antigenicity of TcdB varies between different strains
      of Clostridium difficile. As a result, ribotype-specific forms of TcdB exhibit
      different toxicities and are not strongly cross-neutralized. Using a combination
      of biochemical and immunological approaches, we compared two important variants
      of TcdB (TcdB012 and TcdB027) to identify the mechanisms through which sequence
      differences alter epitopes and activity of the toxin. These analyses led to the
      discovery of a critical variation in the 1753-1851 (B2') region of TcdB, which
      affects the exposure of neutralizing epitopes in the toxin. Sequence comparisons
      found that the B2' region exhibits only 77% identity and is the most variable
      sequence between the two forms of TcdB. A combination of biochemical, analytical,
      and mutagenesis experiments revealed that the B2' region promotes protein-protein
      interactions. These interactions appear to shield neutralizing epitopes that
      would otherwise be exposed in the toxin, an event found to be less prominent in
      TcdB012 due to sequence differences in the 1773-1780 and 1791-1798 regions of the
      B2' domain. When the carboxyl-terminal domains of TcdB012 and TcdB027 are
      swapped, neutralization experiments suggest that the amino terminus of TcdB
      interacts with the B2' region and impacts the exposure of neutralizing epitopes
      in the carboxyl terminus. Collectively, these data suggest that variations in the
      B2' region affect protein-protein interactions within TcdB and that these
      interactions influence the exposure of neutralizing epitopes. 

PMID- 25614626
TI  - The golgi-associated PDZ domain protein PIST/GOPC stabilizes the beta1-adrenergic
      receptor in intracellular compartments after internalization.
AB  - Many G-protein-coupled receptors carry C-terminal ligand motifs for PSD-95/discs
      large/ZO-1 (PDZ) domains; via interaction with PDZ domain-containing scaffold
      proteins, this allows for integration of receptors into signaling complexes.
      However, the presence of PDZ domain proteins attached to intracellular membranes
      suggests that PDZ-type interactions may also contribute to subcellular sorting of
      receptors. The protein interacting specifically with Tc10 (PIST; also known as
      GOPC) is a trans-Golgi-associated protein that interacts through its single PDZ
      domain with a variety of cell surface receptors. Here we show that PIST controls
      trafficking of the interacting beta1-adrenergic receptor both in the anterograde,
      biosynthetic pathway and during postendocytic recycling. Overexpression and
      knockdown experiments show that PIST leads to retention of the receptor in the
      trans-Golgi network (TGN), to the effect that overexpressed PIST reduces
      activation of the MAPK pathway by beta1-adrenergic receptor (beta1AR) agonists.
      Receptors can be released from retention in the TGN by coexpression of the plasma
      membrane-associated scaffold PSD-95, which allows for transport of receptors to
      the plasma membrane. Stimulation of beta1 receptors and activation of the cAMP
      pathway lead to relocation of PIST from the TGN to an endosome-like compartment.
      Here PIST colocalizes with SNX1 and the internalized beta1AR and protects
      endocytosed receptors from lysosomal degradation. In agreement, beta1AR levels
      are decreased in hippocampi of PIST-deficient mice. Our data suggest that PIST
      contributes to the fine-tuning of beta1AR sorting both during biosynthetic and
      postendocytic trafficking. 

PMID- 25614627
TI  - Biased signaling at chemokine receptors.
AB  - The ability of G protein-coupled receptors (GPCRs) to activate selective
      signaling pathways according to the conformation stabilized by bound ligands
      (signaling bias) is a challenging concept in the GPCR field. Signaling bias has
      been documented for several GPCRs, including chemokine receptors. However, most
      of these studies examined the global signaling bias between G protein- and
      arrestin-dependent pathways, leaving unaddressed the potential bias between
      particular G protein subtypes. Here, we investigated the coupling selectivity of
      chemokine receptors CCR2, CCR5, and CCR7 in response to various ligands with G
      protein subtypes by using bioluminescence resonance energy transfer biosensors
      monitoring directly the activation of G proteins. We also compared data obtained
      with the G protein biosensors with those obtained with other functional readouts,
      such as beta-arrestin-2 recruitment, cAMP accumulation, and calcium mobilization
      assays. We showed that the binding of chemokines to CCR2, CCR5, and CCR7
      activated the three Galphai subtypes (Galphai1, Galphai2, and Galphai3) and the
      two Galphao isoforms (Galphaoa and Galphaob) with potencies that generally
      correlate to their binding affinities. In addition, we showed that the binding of
      chemokines to CCR5 and CCR2 also activated Galpha12, but not Galpha13. For each
      receptor, we showed that the relative potency of various agonist chemokines was
      not identical in all assays, supporting the notion that signaling bias exists at
      chemokine receptors. 

PMID- 25614628
TI  - Identification and characterization of a novel prokaryotic peptide: N-glycosidase
      from Elizabethkingia meningoseptica.
AB  - Peptide:N-glycosidase (PNGase) F, the first PNGase identified in prokaryotic
      cells, catalyzes the removal of intact asparagine-linked oligosaccharide chains
      from glycoproteins and/or glycopeptides. Since its discovery in 1984, PNGase F
      has remained as the sole prokaryotic PNGase. Recently, a novel gene encoding a
      protein with a predicted PNGase domain was identified from a clinical isolate of
      Elizabethkingia meningoseptica. In this study, the candidate protein was
      expressed in vitro and was subjected to biochemical and structural analyses. The
      results revealed that it possesses PNGase activity and has substrate specificity
      different from that of PNGase F. The crystal structure of the protein was
      determined at 1.9 A resolution. Structural comparison with PNGase F revealed a
      relatively larger glycan-binding groove in the catalytic domain and an additional
      bowl-like domain with unknown function at the N terminus of the candidate
      protein. These structural and functional analyses indicated that the candidate
      protein is a novel prokaryotic N-glycosidase. The protein has been named PNGase F
      II. 

PMID- 25614631
TI  - Assessment of annual average effective dose status in the cohort of medical staff
      in Lithuania during 1991-2013.
AB  - The use of radiation sources for various medical purposes is closely related to
      irradiation of the medical staff, which causes harmful effects to health and an
      increased risk of cancer. In total, 1463 medical staff who have been
      occupationally exposed to sources of ionising radiation (IR) had been monitored.
      Records with annual dose measurements (N = 19 157) were collected and regularly
      analysed for a 23-y period: from 01 January 1991 to 31 December 2013. The
      collected annual average effective dose (AAED) data have been analysed according
      to different socio-demographic parameters and will be used in future
      investigation in order to assess cancer risk among medical staff occupationally
      exposed to sources of IR. A thorough analysis of data extracted from medical
      staff's dose records allows one to conclude that the average annual effective
      dose of Lithuanian medical staff occupationally exposed to sources of IR was
      consistently decreased from 1991 (1.75 mSv) to 2013 (0.27 mSv) (p < 0.0001).

PMID- 25614629
TI  - Dynamic regulation of Schwann cell enhancers after peripheral nerve injury.
AB  - Myelination of the peripheral nervous system is required for axonal function and
      long term stability. After peripheral nerve injury, Schwann cells transition from
      axon myelination to a demyelinated state that supports neuronal survival and
      ultimately remyelination of axons. Reprogramming of gene expression patterns
      during development and injury responses is shaped by the actions of distal
      regulatory elements that integrate the actions of multiple transcription factors.
      We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of
      active enhancers, to identify enhancers in myelinating rat peripheral nerve and
      their dynamics after demyelinating nerve injury. Analysis of injury-induced
      enhancers identified enriched motifs for c-Jun, a transcription factor required
      for Schwann cells to support nerve regeneration. We identify a c-Jun-bound
      enhancer in the gene for Runx2, a transcription factor induced after nerve
      injury, and we show that Runx2 is required for activation of other induced genes.
      In contrast, enhancers that lose H3K27ac after nerve injury are enriched for
      binding sites of the Sox10 and early growth response 2 (Egr2/Krox20)
      transcription factors, which are critical determinants of Schwann cell
      differentiation. Egr2 expression is lost after nerve injury, and many Egr2
      binding sites lose H3K27ac after nerve injury. However, the majority of Egr2
      bound enhancers retain H3K27ac, indicating that other transcription factors
      maintain active enhancer status after nerve injury. The global epigenomic changes
      in H3K27ac deposition pinpoint dynamic changes in enhancers that mediate the
      effects of transcription factors that control Schwann cell myelination and
      peripheral nervous system responses to nerve injury. 

PMID- 25614630
TI  - A dualistic conformational response to substrate binding in the human serotonin
      transporter reveals a high affinity state for serotonin.
AB  - Serotonergic neurotransmission is modulated by the membrane-embedded serotonin
      transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic
      neurons. Conformational changes in SERT occur upon binding of ions and substrate
      and are crucial for translocation of serotonin across the membrane. Our
      understanding of these conformational changes is mainly based on crystal
      structures of a bacterial homolog in various conformations, derived homology
      models of eukaryotic neurotransmitter transporters, and substituted cysteine
      accessibility method of SERT. However, the dynamic changes that occur in the
      human SERT upon binding of ions, the translocation of substrate, and the role of
      cholesterol in this interplay are not fully elucidated. Here we show that
      serotonin induces a dualistic conformational response in SERT. We exploited the
      substituted cysteine scanning method under conditions that were sensitized to
      detect a more outward-facing conformation of SERT. We found a novel high affinity
      outward-facing conformational state of the human SERT induced by serotonin. The
      ionic requirements for this new conformational response to serotonin mirror the
      ionic requirements for translocation. Furthermore, we found that membrane
      cholesterol plays a role in the dualistic conformational response in SERT induced
      by serotonin. Our results indicate the existence of a subpopulation of SERT
      responding differently to serotonin binding than hitherto believed and that
      membrane cholesterol plays a role in this subpopulation of SERT. 

PMID- 25614632
TI  - Evaluation of occupational exposure to ELF magnetic fields at power plants in
      Greece in the context of European directives.
AB  - The scope of this paper is to comparatively present the extremely low-frequency
      (ELF) measurements performed at four power plants in Greece, focusing on: (a) the
      worst-case exposure conditions, (b) the existence of magnetic field harmonic
      components, (c) the technical similarities among the power plants and (d)
      comparison of the measured percentages of reference levels at typical working
      areas in the power plants. A detailed measurement methodology is proposed,
      including broadband on-site inspection of the working areas, weighted averaged
      root-mean-square and peak values of magnetic flux density, percentage of
      reference levels, according to 1998 ICNIRP guidelines and harmonic analysis of
      the multi-frequency magnetic fields. During the analysis of the occupational
      exposure in all power plants, the new Directive 2013/35/EU has been taken into
      account. The study concludes by proposing a mapping procedure of working areas
      into certain zones, in order to take measures for workers safety.

PMID- 25614633
TI  - STAT3: too much may be worse than not enough!

PMID- 25614634
TI  - Myeloid disorders arise in Dnmt3a-null marrow.

PMID- 25614635
TI  - Enhancing BCR signals at the cell membrane.

PMID- 25614636
TI  - Mutations and microenvironment collude in FL.

PMID- 25614637
TI  - The vascular side of plasma kallikrein.

PMID- 25614638
TI  - Carbon monoxide poisoning and risk of deep vein thrombosis and pulmonary
      embolism: a nationwide retrospective cohort study.
AB  - BACKGROUND: Few studies have investigated the relationship between carbon
      monoxide (CO) poisoning and risk of deep vein thrombosis (DVT) and pulmonary
      embolism (PE). Therefore, we conducted a nationwide longitudinal cohort study in
      Taiwan to determine whether patients with CO poisoning are associated with
      increased risk of developing DVT and PE. METHODS: This study investigated the
      incidence and risk factors for DVT and PE in 8316 patients newly diagnosed with
      CO poisoning from the Taiwan National Health Insurance Research Database between
      2000 and 2011. The comparison cohort contained 33 264 controls without CO
      poisoning from the general population. Follow-up was initiated on the date of
      initial diagnosis of CO poisoning and continued until the date of a DVT or PE
      event, censoring or December 31, 2011. Cox proportional hazard regression models
      were used to analyse the risk of DVT and PE according to sex, age and
      comorbidities. RESULTS: The incidences of DVT and PE were higher in the patients
      with CO poisoning than in the controls (5.67 vs 1.47/10 000 person-years and 1.97
      vs 1.02/10 000 person-years, respectively). After adjusting for age, sex and
      comorbidities, the patients with CO poisoning were associated with a 3.85-fold
      higher risk of DVT compared with the comparison cohort, and non-significantly
      associated with risk of PE. CO poisoning patients with a coexisting comorbidity
      or acute respiratory failure were associated with significantly and substantially
      increased risk of DVT. CONCLUSION: Risk of DVT is significantly higher in
      patients with CO poisoning than in the general population.

PMID- 25614639
TI  - A closer look at the role of healthcare in the recent mortality decline in the
      Netherlands: results of a record linkage study.
AB  - BACKGROUND: Since 2002, Dutch mortality rates decreased rapidly after decades of
      stagnation. On the basis of indirect evidence, previous research has suggested
      that this decline was due to a sudden expansion of healthcare. We tested two
      corollaries of this hypothesis--first, that the decline was concentrated among
      those with ill-health and second, that the decline can be statistically accounted
      for by increases in healthcare utilisation. METHODS: We linked the Dutch health
      interview survey to the mortality register and constructed two cohorts,
      consisting of 7691 persons interviewed in 2001/2002 and 8362 persons interviewed
      in 2007/2008, each with a 5-year mortality follow-up (659 deaths in total). The
      change in mortality between both cohorts was computed using Cox proportional
      hazard models. We estimated the change in mortality by severity of chronic
      conditions and with respect to the inclusion of indicators of healthcare
      utilisation. RESULTS: Between the two study cohorts, mortality declined by 15%
      (95% CI 2% to 29%), and mortality reduction was greatest for those suffering from
      fatal and non-fatal conditions with a decline of 58% (95% CI 35% to 78%). Even
      after adjustment for health status and risk factors, most indicators of
      healthcare utilisation were associated with higher instead of lower mortality and
      changes in healthcare utilisation did not explain the decline in mortality.
      CONCLUSIONS: Our results only partly confirm the hypothesis that an expansion of
      healthcare explains the recent mortality decline in the Netherlands. Owing to
      confounding by health status, it is difficult to reproduce the mortality-lowering
      effects of healthcare utilisation of individual level studies in the open
      population.

PMID- 25614640
TI  - Can the next generation of clinician-scientists please step forward?

PMID- 25614642
TI  - Smoking and mental illness.

PMID- 25614645
TI  - Tobacco plain packaging and smoking rates in Australia.

PMID- 25614646
TI  - Re: Meeting Dr Jekyll.

PMID- 25614647
TI  - Mixed emotions: a response to--Large MM and Ryan CJ. Suicide risk categorisation
      of psychiatric inpatients: what it might mean and why it is of no use.

PMID- 25614658
TI  - Wounding tomato fruit elicits ripening-stage specific changes in gene expression
      and production of volatile compounds.
AB  - Fleshy fruits develop from an unripe organ that needs to be protected from damage
      to a ripe organ that attracts frugivores for seed dispersal through production of
      volatile organic compounds (VOCs). Thus, different responses to wounding damage
      are predicted. The aim of this study was to discover whether wound-induced
      changes in the transcriptome and VOC production alter as tomato transitions from
      unripe to ripe. Transcript changes were analysed 3h post-wounding using
      microarray analysis in two commercial salad-tomato (Solanum lycopersicum L.)
      cultivars: Luna Rossa and AVG, chosen for their high aroma production. This was
      followed by quantitative PCR on Luna Rossa genes involved in VOC biosynthesis and
      defence responses. VOCs elicited by wounding at different ripening stages were
      analysed by solid phase micro extraction and gas chromatography-mass
      spectrometry. Approximately 4000 differentially expressed genes were identified
      in the cultivar AVG and 2500 in Luna Rossa. In both cultivars the majority of
      genes were up-regulated and the most affected pathways were metabolism of
      terpenes, carotenoids, and lipids. Defence-related genes were mostly up-regulated
      in immature stages of development, whereas expression of genes related to VOCs
      changed at riper stages. More than 40 VOCs were detected and profiles changed
      with ripening stage. Thus, both transcriptome and VOC profiles elicited by
      wounding depend on stage of ripening, indicating a shift from defence to
      attraction. 

PMID- 25614659
TI  - Improving barley culm robustness for secured crop yield in a changing climate.
AB  - The Green Revolution combined advancements in breeding and agricultural practice,
      and provided food security to millions of people. Daily food supply is still a
      major issue in many parts of the world and is further challenged by future
      climate change. Fortunately, life science research is currently making huge
      progress, and the development of future crop plants will be explored. Today,
      plant breeding typically follows one gene per trait. However, new scientific
      achievements have revealed that many of these traits depend on different genes
      and complex interactions of proteins reacting to various external stimuli. These
      findings open up new possibilities for breeding where variations in several genes
      can be combined to enhance productivity and quality. In this review we present an
      overview of genes determining plant architecture in barley, with a special focus
      on culm length. Many genes are currently known only through their mutant
      phenotypes, but emerging genomic sequence information will accelerate their
      identification. More than 1000 different short-culm barley mutants have been
      isolated and classified in different phenotypic groups according to culm length
      and additional pleiotropic characters. Some mutants have been connected to
      deficiencies in biosynthesis and reception of brassinosteroids and gibberellic
      acids. Still other mutants are unlikely to be connected to these hormones. The
      genes and corresponding mutations are of potential interest for development of
      stiff-straw crop plants tolerant to lodging, which occurs in extreme weather
      conditions with strong winds and heavy precipitation. 

PMID- 25614661
TI  - Breeding crops for improved mineral nutrition under climate change conditions.
AB  - Improvements in understanding how climate change may influence chemical and
      physical processes in soils, how this may affect nutrient availability, and how
      plants may respond to changed availability of nutrients will influence crop
      breeding programmes. The effects of increased atmospheric CO2 and warmer
      temperatures, both individually and combined, on soil microbial activity,
      including mycorrhizas and N-fixing organisms, are evaluated, together with their
      implications for nutrient availability. Potential changes to plant growth, and
      the combined effects of soil and plant changes on nutrient uptake, are discussed.
      The organization of research on the efficient use of macro- and micronutrients by
      crops under climate change conditions is outlined, including analysis of QTLs for
      nutrient efficiency. Suggestions for how the information gained can be used in
      plant breeding programmes are given. 

PMID- 25614660
TI  - The NPR1-dependent salicylic acid signalling pathway is pivotal for enhanced salt
      and oxidative stress tolerance in Arabidopsis.
AB  - The role of endogenous salicylic acid (SA) signalling cascades in plant responses
      to salt and oxidative stresses is unclear. Arabidopsis SA signalling mutants,
      namely npr1-5 (non-expresser of pathogenesis related gene1), which lacks NPR1
      dependent SA signalling, and nudt7 (nudix hydrolase7), which has both
      constitutively expressed NPR1-dependent and NPR1-independent SA signalling
      pathways, were compared with the wild type (Col-0) during salt or oxidative
      stresses. Growth and viability staining showed that, compared with wild type, the
      npr1-5 mutant was sensitive to either salt or oxidative stress, whereas the nudt7
      mutant was tolerant. Acute salt stress caused the strongest membrane potential
      depolarization, highest sodium and proton influx, and potassium loss from npr1-5
      roots in comparison with the wild type and nudt7 mutant. Though salt stress
      induced hydrogen peroxide production was lowest in the npr1-5 mutant, the
      reactive oxygen species (ROS) stress (induced by 1mM of hydroxyl-radical
      generating copper-ascorbate mix, or either 1 or 10mM hydrogen peroxide) caused a
      higher potassium loss from the roots of the npr1-5 mutant than the wild type and
      nudt7 mutant. Long-term salt exposure resulted in the highest sodium and the
      lowest potassium concentration in the shoots of npr1-5 mutant in comparison with
      the wild type and nudt7 mutant. The above results demonstrate that NPR1-dependent
      SA signalling is pivotal to (i) controlling Na(+) entry into the root tissue and
      its subsequent long-distance transport into the shoot, and (ii) preventing a
      potassium loss through depolarization-activated outward-rectifying potassium and
      ROS-activated non-selective cation channels. In conclusion, NPR1-dependent SA
      signalling is central to the salt and oxidative stress tolerance in Arabidopsis. 

PMID- 25614663
TI  - Planning for food security in a changing climate.
AB  - The Intergovernmental Panel on Climate Change and other international agencies
      have concluded that global crop production is at risk due to climate change,
      population growth, and changing food preferences. Society expects that the
      agricultural sciences will innovate solutions to these problems and provide food
      security for the foreseeable future. My thesis is that an integrated research
      plan merging agronomic and genetic approaches has the greatest probability of
      success. I present a template for a research plan based on the lessons we have
      learned from the Green Revolution and from the development of genetically
      engineered crops that may guide us to meet this expectation. The plan starts with
      a vision of how the crop management system could change, and I give a few
      examples of innovations that are very much in their infancy but have significant
      potential. The opportunities need to be conceptualized on a regional basis for
      each crop to provide a target for change. The plan gives an overview of how the
      tools of plant biotechnology can be used to create the genetic diversity needed
      to implement the envisioned changes in the crop management system, using the
      development of drought tolerance in maize (Zea mays L.) as an example that has
      led recently to the commercial release of new hybrids in the USA. The plan
      requires an interdisciplinary approach that integrates and coordinates research
      on plant biotechnology, genetics, physiology, breeding, agronomy, and cropping
      systems to be successful. 

PMID- 25614662
TI  - Soybean kinome: functional classification and gene expression patterns.
AB  - The protein kinase (PK) gene family is one of the largest and most highly
      conserved gene families in plants and plays a role in nearly all biological
      functions. While a large number of genes have been predicted to encode PKs in
      soybean, a comprehensive functional classification and global analysis of
      expression patterns of this large gene family is lacking. In this study, we
      identified the entire soybean PK repertoire or kinome, which comprised 2166
      putative PK genes, representing 4.67% of all soybean protein-coding genes. The
      soybean kinome was classified into 19 groups, 81 families, and 122 subfamilies.
      The receptor-like kinase (RLK) group was remarkably large, containing 1418 genes.
      Collinearity analysis indicated that whole-genome segmental duplication events
      may have played a key role in the expansion of the soybean kinome, whereas tandem
      duplications might have contributed to the expansion of specific subfamilies.
      Gene structure, subcellular localization prediction, and gene expression patterns
      indicated extensive functional divergence of PK subfamilies. Global gene
      expression analysis of soybean PK subfamilies revealed tissue- and stress
      specific expression patterns, implying regulatory functions over a wide range of
      developmental and physiological processes. In addition, tissue and stress co
      expression network analysis uncovered specific subfamilies with narrow or wide
      interconnected relationships, indicative of their association with particular or
      broad signalling pathways, respectively. Taken together, our analyses provide a
      foundation for further functional studies to reveal the biological and molecular
      functions of PKs in soybean. 

PMID- 25614665
TI  - Deciphering metabolic messages from the gut drives therapeutic innovation: the
      2014 Banting Lecture.
AB  - The Banting Medal for Scientific Achievement is the highest scientific award of
      the American Diabetes Association (ADA). Given in memory of Sir Frederick
      Banting, one of the key investigators in the discovery of insulin, the Banting
      Medal is awarded annually for scientific excellence, recognizing significant long
      term contributions to the understanding, treatment, or prevention of diabetes.
      Daniel J. Drucker, MD, of the Department of Medicine, Mount Sinai Hospital and
      the Lunenfeld-Tanenbaum Research Institute in Toronto, Ontario, Canada, received
      the prestigious award at the ADA's 74th Scientific Sessions, 13-17 June 2014, in
      San Francisco, California. He presented the Banting Lecture, "Deciphering
      Metabolic Messages From the Gut Drives Therapeutic Innovation," on Sunday, 15
      June 2014.Gut peptides convey nutrient-regulated signals to the enteric nervous
      system and to distal organs, acting as circulating hormones secreted in the basal
      and postprandial state. Here I provide an overview of the actions of glucagon
      like peptide (GLP)-1 and GLP-2, the two major enteroendocrine L-cell peptides.
      The endogenous physiological actions of GLP-1 have been delineated using
      antagonists and Glp1r(-/-) mice and include the control of islet hormone
      secretion in a glucose-dependent manner, leading to improvement of fasting and
      postprandial glucose homeostasis. GLP-1 receptors (GLP-1Rs) are also widely
      distributed in multiple extrapancreatic organs, providing a mechanistic
      explanation for the nonglycemic actions attributed to GLP-1. The multiple
      metabolic actions of GLP-1 enable reduction of glycemia and body weight in
      diabetic and obese subjects, providing the opportunity to reduce glycemia in
      human subjects with diabetes with a low risk of hypoglycemia. GLP-2 plays a key
      role in the control of energy absorption and in the integrity of the intestinal
      mucosa, and a GLP-2R agonist, teduglutide, is now used for augmentation of energy
      absorption in parenteral nutrition-dependent subjects with short bowel syndrome.
      GLP-1 and GLP-2 are both cleaved by dipeptidyl peptidase-4 (DPP-4); hence,
      inhibition of DPP-4 activity enables yet another pathway for potentiation of
      incretin action and the therapy for type 2 diabetes. Here I review our 30-year
      experience with the elucidation of gut hormone action and, wherever possible,
      highlight therapeutic implications of our preclinical studies and future
      opportunities for incretin research. 

PMID- 25614667
TI  - Why do exercise and dietary restriction during pregnancy affect glucose tolerance
      in opposite ways?

PMID- 25614666
TI  - New insights into gestational glucose metabolism: lessons learned from 21st
      century approaches.
AB  - Pregnancy presents a unique physiological challenge that requires changes
      coordinated by placentally and non-placentally derived hormones to prepare the
      mother for the metabolic stress presented by fetal development and to ensure
      appropriate nutrient allocation between mother and fetus. Of particular
      importance is the maintenance of normal glucose metabolism during pregnancy.
      Here, we describe physiological changes in glucose metabolism during pregnancy
      and highlight new insights into these adaptations that have emerged over the past
      decade using novel methodologies, specifically genome-wide association studies
      (GWAS) and metabolomics. While GWAS have identified some novel associations with
      metabolic traits during pregnancy, the majority of the findings overlap with
      those observed in nonpregnant populations and individuals with type 2 diabetes
      (T2D). Metabolomics studies have provided new insight into key metabolites
      involved in gestational diabetes mellitus (GDM). Both of these approaches have
      suggested that a strong link exists between GDM and T2D. Most recently, a role of
      the gut microbiome in pregnancy has been observed, with changes in the microbiome
      during the third trimester having metabolic consequences for the mother. In this
      Perspectives in Diabetes article, we highlight how these new data have broadened
      our understanding of gestational metabolism, and emphasize the importance of
      future studies to elucidate differences between GDM and T2D. 

PMID- 25614668
TI  - An absorbing sense of sweetness.

PMID- 25614669
TI  - Further insight on the limits of success of glycemic control in type 1 diabetes.

PMID- 25614670
TI  - ATGL-catalyzed lipolysis regulates SIRT1 to control PGC-1alpha/PPAR-alpha
      signaling.
AB  - Sirtuin 1 (SIRT1), an NAD(+)-dependent protein deacetylase, regulates a host of
      target proteins, including peroxisome proliferator-activated receptor (PPAR)
      gamma coactivator-1alpha (PGC-1alpha), a transcriptional coregulator that binds
      to numerous transcription factors in response to deacetylation to promote
      mitochondrial biogenesis and oxidative metabolism. Our laboratory and others have
      shown that adipose triglyceride lipase (ATGL) increases the activity of the
      nuclear receptor PPAR-alpha, a PGC-1alpha binding partner, to promote fatty acid
      oxidation. Fatty acids bind and activate PPAR-alpha; therefore, it has been
      presumed that fatty acids derived from ATGL-catalyzed lipolysis act as PPAR-alpha
      ligands. We provide an alternate mechanism that links ATGL to PPAR-alpha
      signaling. We show that SIRT1 deacetylase activity is positively regulated by
      ATGL to promote PGC-1alpha signaling. In addition, ATGL mediates the effects of
      beta-adrenergic signaling on SIRT1 activity, and PGC-1alpha and PPAR-alpha target
      gene expression independent of changes in NAD(+). Moreover, SIRT1 is required for
      the induction of PGC-1alpha/PPAR-alpha target genes and oxidative metabolism in
      response to increased ATGL-mediated lipolysis. Taken together, this work
      identifies SIRT1 as a critical node that links beta-adrenergic signaling and
      lipolysis to changes in the transcriptional regulation of oxidative metabolism. 

PMID- 25614672
TI  - Comment on Malik. Which test for diagnosing early human diabetic neuropathy?
      Diabetes 2014;63:2206-2208.

PMID- 25614673
TI  - Response to comment on Malik. Which test for diagnosing early human diabetic
      neuropathy? Diabetes 2014;63:2206-2208.

PMID- 25614674
TI  - [The role of SIRT1 in the pathogenesis of insulin resistance in skeletal muscle].
AB  - Skeletal muscle insulin resistance manifests as a decreased ability of insulin to
      stimulate glucose uptake in consequence of an impairment in its intracellular
      signaling. Sirtuin 1 (SIRT1), which belongs to the family of sirtuins (Sir2;
      silent information regulator 2 protein) participates in the regulation of
      skeletal muscle glucose and lipid metabolism. Experimental studies indicate that
      SIRT1 may play a role in the pathogenesis of skeletal muscle insulin resistance.
      SIRT1 directly influences insulin signal transduction pathway. It increases
      insulin-dependent IRS2 phosphorylation and Akt activation. Moreover, SIRT1
      interacts with PGC1alpha and AMPK to stimulate muscle glucose uptake and fatty
      acid oxidation and thus it can prevent insulin resistance. SIRT1 activators might
      be useful in the treatment of insulin resistance-related diseases. 

PMID- 25614675
TI  - [Hypothermia--mechanism of action and pathophysiological changes in the human
      body].
AB  - This review focuses on the physiological responses and pathophysiological changes
      induced by hypothermia. Normal body function depends on its ability to maintain
      thermal homeostasis. The human body can be divided arbitrarily into two thermal
      compartments: a core compartment (trunk and head), with precisely regulated
      temperature around 37 degrees C, and a peripheral compartment (skin and
      extremities) with less strictly controlled temperature, and lower than the core
      temperature. Thermoregulatory processes occur in three phases: afferent thermal
      sensing, central regulation, mainly by the preoptic area of the anterior
      hypothalamus, and efferent response. Exposure to cold induces thermoregulatory
      responses including cutaneous vasoconstriction, shivering and non-shivering
      thermogenesis, and behavioral changes. Alterations of body temperature associated
      with impaired thermoregulation, decreased heat production or increased heat loss
      can lead to hypothermia. Hypothermia is defined as a core body temperature below
      35oC, and may be classified according to the origin as accidental (e.g. caused by
      exposure to a cold environment, drugs, or illness) or intentional (i.e.
      therapeutic), or by the degree of hypothermia as mild, moderate or severe.
      Classification by temperature is not universal. Lowering of body temperature
      disrupts the physiological processes at the molecular, cellular and system level,
      but hypothermia induced prior to cardiosurgical or neurosurgical procedures, by
      the decrease in tissue oxygen demand, can reduce the risk of cerebral or cardiac
      ischemic damage. Therapeutic hypothermia has been recommended as a clinical
      procedure in situations characterized by ischemia, such as cardiac arrest, stroke
      and brain injuries. 

PMID- 25614676
TI  - [Metabolic disorders and nutritional status in autoimmune thyroid diseases].
AB  - In recent years, the authors of epidemiological studies have documented that
      autoimmune diseases are a major problem of modern society and are classified as
      diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an
      abnormal immune response to autoantigens present in the thyroid gland - they
      often coexist with other autoimmune diseases. The most common dysfunctions of the
      thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease.
      Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the
      thyroid gland. Anthropometric, biochemical and physicochemical parameters are
      used to assess the nutritional status during the diagnosis and treatment of
      thyroid diseases. Patients with hypothyroidism are often obese, whereas patients
      with hyperthyroidism are often afflicted with rapid weight loss. The consequence
      of obesity is a change of the thyroid hormones' activity; however, weight
      reduction leads to their normalization. The activity and metabolic rate of
      thyroid hormones are modifiable. ATDs are associated with abnormalities of
      glucose metabolism and thus increased risk of developing diabetes mellitus type 1
      and type 2. Celiac disease (CD) also increases the risk of developing other
      autoimmune diseases. Malnutrition or the presence of numerous nutritional
      deficiencies in a patient's body can be the cause of thyroid disorders.
      Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may
      impair the function of the thyroid gland. Other nutrient deficiencies usually
      observed in patients suffering from ATD are: protein deficiencies, vitamin
      deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium,
      potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the
      disease, maintains a healthy weight and prevents the occurrence of malnutrition.
      This article presents an overview of selected documented studies and scientific
      reports on the relationship of metabolic disorders and nutritional status with
      the occurrence of ATD. 

PMID- 25614677
TI  - [Immunomodulatory and antitumor properties of polysaccharide peptide (PSP)].
AB  - Modern medicine successfully uses multiple immunomodulators of natural origin,
      that can affect biological reactions and support body's natural defense
      mechanisms including antitumor activities. Among them is a group of products
      derived from fungi, including schizophyllan, lentinan, polysaccharide Krestin
      (PSK), and polysaccharidepeptide (PSP). Present paper is focused on
      polysaccharidepeptide, which due to the negligible toxicity and numerous benefits
      for health, is increasingly used in China and Japan as an adjuvant in the
      treatment of cancer. PSP is a protein-polisaccharide complex with a molecular
      weight 100 kDa derived from Coriolus versicolor mushroom. The results of numerous
      studies and clinical trials confirm that it inhibits the growth of cancer cells
      in in vitro and in vivo settings as well as decreases cancer treatment-related
      adverse side effects such as fatigue, loss of appetite, nausea, vomiting, and
      pain. PSP is able to restore weakened immune response observed in patients with
      cancer during chemotherapy. Its anti-tumor effects seemed to be mediated through
      immunomodulatory regulation. PSP stimulates cells of the immune system, induces
      synthesis of cytokines such as interleukin-1beta (IL-1beta), IL-6 and tumor
      necrosis factor-alpha (TNF-alpha), eicosanoids including prostaglandin E2 (PGE2),
      histamine, reactive oxygen species and nitrogen mediators. There is a growing
      interest in understanding the mechanisms of PSP action. Because of its unique
      properties and safety, PSP may become a widely used therapeutic agent in the near
      future. 

PMID- 25614678
TI  - [Uroplakins as markers of diseases of the urinary system].
AB  - An unique element of bladder urothelium is a multilayer membrane, which extends
      from the renal pelvis to the urethra. Urotelial membrane covers more than 90% of
      the inner portion of the bladder and is in direct contact with urine. Urothelium
      is composed of characteristic two-dimensional, asymmetric plaques, composed of
      uroplakins (UP), differentiated, hexagonally arranged proteins. The unique
      structure of the urothelial plaques determines the tightness, integrity and
      strength of the urothelium, prevent rupture of the walls of the bladder during
      the build-up of urine in the bladder and protects against the toxic ingredients.
      Uroplakins are tissue-specific, heterogeneous glycoproteins whose oligosaccharide
      part plays a specific role in the structure and function of urothelium. Disorders
      of normal expression of uroplakins are highly associated with the pathogenesis in
      infection and urinary tract malignancies, primary vesico-urinary reflux,
      hydronephrosis and renal impairment. The emergence of uroplakins in urine and /
      or plasma may have a potential role in the early detection of bladder tumors. In
      this paper, the structure and function of uroplakins types Ia, Ib, II, IIIa,
      their natural oligomerization into heterodimers, tetramers and hexamers, and the
      role in the construction of asymmetric and flexible urothelial epithelium is
      presented. We discuss the potential role of uroplakins in laboratory diagnosis of
      umbrella cell differentiation and in the screening analysis of urinary bladder
      disorders. The possibilities of using the knowledge of uroplakins in clinical
      settings as well as in modern strategies for treatment of infectious diseases and
      cancer of the urinary tract are highlighted. 

PMID- 25614679
TI  - [Lysis of bacterial cells in the process of bacteriophage release--canonical and
      newly discovered mechanisms].
AB  - The release of phage progeny from an infected bacterium is necessary for the
      spread of infection. Only helical phages are secreted from a cell without causing
      its destruction. The release of remaining phages is correlated with bacterial
      lysis and death. Thus, the understanding of phage lytic functions is crucial for
      their use in the fight with bacterial pathogens. Bacteriophages with small RNA or
      DNA genomes encode single proteins which are called amurins and cause lysis by
      the inhibition of cell wall synthesis. Bacteriophages of double-stranded DNA
      genomes, which dominate in the environment, encode enzymes that are called
      endolysins and contribute to lysis by the cleavage of cell wall peptydoglycan.
      Endolysins that do not contain signal sequences cannot pass the cytoplasmic
      membrane by themselves. Their access to peptidoglycan is provided by membrane
      proteins - holins, which can form in the membrane large pores, that are called
      "holes". Some endolysins do not require holins for their transport, owing to the
      presence of the so called SAR sequence at their N-terminus. It enables their
      transport through the membrane by the bacterial sec system. However, it is not
      cleaved off, and thus these endolysins remain trapped in the membrane in an
      inactive form. Their release, which is correlated with the activation, occurs as
      a result of membrane depolarization and depends on proteins that are called
      pinholins. Pinholins form in membrane pores that are too small for the passage of
      endolysins but sufficient for membrane depolarization. Proteins that are called
      antiholins regulate the timing of lysis, through the blockage of holins action
      until the end of phage morphogenesis. Additionally, newly identified lytic
      proteins, spanins, participate in the release of progeny phages from Gram
      negative bacteria cells. They cause the destruction of outer cell membrane by its
      spanning with the cytoplasmic membrane. This is possible after the endolysin
      mediated destruction of peptidoglycan, which separates both membranes, and
      ensures the fast completion of lysis. 

PMID- 25614680
TI  - [The phenomenon of vitamin D].
AB  - The receptor of vitamin D (VDR) is present in most non-skeletal human cells,
      suggesting its role beyond the bone and calcium metabolism. The relationship
      between vitamin D and the respiratory tract is a consequence of its activity in
      the immune system. Some gastrointestinal diseases, such as inflammatory bowel
      disease, coeliac disease, liver, pancreas or cardiac diseases, lead to vitamin D
      deficiency. Many studies indicate a correlation between vitamin D and diabetes.
      VDR and 1alpha-hydroxylase have been detected in the cutaneous capillary vessels,
      endothelium, vascular smooth muscles, myocytes and cardiac fibroblasts. The
      influence of vitamin D on the expression of genes related to the vascular walls
      implies its role in the pathomechanisms of vascular diseases and the
      cardiovascular system. Due to the VDR detected in most immunocompetent cells,
      calcitriol can modulate the congenital and acquired immune system. The
      correlation between vitamin D and cancer development is also not surprising
      because of many functions which vitamin D has in the organism. The vitamin D
      regulated genes encode the proteins which participate in differentiation,
      proliferation or apoptosis. This paper aims to focus on the less well known roles
      of vitamin D in the organism, especially considering that most "sun consumers"
      know only its antirachitic and bone reinforcing action. So, this article may be
      surprising, and first of all it should convince everyone to vitamin D
      supplemention. 

PMID- 25614681
TI  - [When defense becomes dangerous--transcription factor Nrf2 and cancer].
AB  - The transcription factor Nrf2 controls the expression of genes encoding
      cytoprotective enzymes and proteins. Its activation is related to conformational
      changes in the inhibitory protein Keap1 and/or Nrf2 phosphorylation by upstream
      kinases. Activation of Nrf2 can lead to the induction of phase II enzymes
      responsible for the inactivation of potential carcinogens. This may constitute an
      important strategy of chemoprevention. Moreover, these enzymatic systems
      participating in the biotransformation of drugs can reduce their therapeutic
      effects, contributing to drug resistance. For this reason, a clear understanding
      of the role of Nrf2 is essential to assess the beneficial and adverse effects of
      its up-regulation, particularly in relation to the prevention and treatment of
      cancer. This article summarizes the current state of knowledge on the
      significance of Nrf2 in tumorigenesis. 

PMID- 25614683
TI  - Successive spin polarizations underlying a new magnetic coupling contribution in
      diluted magnetic semiconductors.
AB  - We propose a new type of magnetic coupling (MC) that is found in diluted magnetic
      semiconductors (DMSs). The origin of this is found to be the result of charge
      transfer processes followed by successive spin polarizations (SSPs) along
      successive cation-anion segments which include the impurities. The basic process
      underlying the SSP-based MC (SSP-MC) is the sharing of a single spin orbital by
      two neighboring impurities. As such, it can be considered as a localized double
      exchange as it is not mediated by free carriers. SSP-MC can be either
      ferromagnetic (SSP-FMC) or antiferromagnetic (SSP-AFMC) and, as demonstrated
      here, the SSP-FMC can be significantly enhanced via codoping; it can act in
      competition with superexchange and/or double and/or p-d exchange interactions.
      While the SSP-MC is not directly related to the magnitude of the magnetic moments
      of the impurities, it depends strongly on the energy difference of the host and
      impurity d-band centers, the difference of their electronegativities and rather
      weakly on the coupling interactions between them as well as between the cations
      and their mediating anions. The validity of the proposed SSP-MC as a new type of
      magnetic coupling is demonstrated by ab initio results for DMSs, namely ZnO, GaN,
      GaP, TiO2 and MoS2 monodoped (with Co, Cu and Mn) and codoped (with Co-Cu-Co and
      Mn-Cu-Mn). 

PMID- 25614684
TI  - Thickness tunable quantum interference between surface phonon and Dirac plasmon
      states in thin films of the topological insulator Bi2Se3.
AB  - We report on a >100-fold enhancement of Raman responses from Bi2Se3 thin films if
      laser photon energy switches from 2.33 eV (532 nm) to 1.58 eV (785 nm), which is
      due to direct optical coupling to Dirac surface states (SS) at the resonance
      energy of ~1.5 eV (a thickness-independent enhancement) and due to nonlinearly
      excited Dirac plasmon (a thickness-dependent enhancement). Owing to the direct
      optical coupling, we observed an in-plane phonon mode of hexagonally arranged Se
      atoms associated with a continuous network of Dirac SS. This mode revealed a Fano
      lineshape for films <15 nm thick, resulting from quantum interference between
      surface phonon and Dirac plasmon states.

PMID- 25614682
TI  - The progesterone antagonist mifepristone/RU486 blocks the negative effect on life
      span caused by mating in female Drosophila.
AB  - Mating causes decreased life span in female Drosophila. Here we report that
      mifepristone blocked this effect, yielding life span increases up to +68%. Drug
      was fed to females after mating, in the absence of males, demonstrating function
      in females. Mifepristone did not increase life span of virgin females or males.
      Mifepristone reduced progeny production but did not reduce food intake. High
      throughput RNA sequencing was used to identify genes up-regulated or down
      regulated upon mating, and where the change was reduced by mifepristone. Five
      candidate positive regulators of life span were identified, including dosage
      compensation regulator Unr and three X-linked genes: multi sex combs (PcG gene),
      Dopamine 2-like receptor and CG14215. The 37 candidate negative genes included
      neuropeptide CNMamide and several involved in protein mobilization and immune
      response. The results inform the interpretation of experiments involving
      mifepristone, and implicate steroid hormone signaling in regulating the trade-off
      between reproduction and life span. 

PMID- 25614685
TI  - Determination of gradient elastic tensors: stress and strain dependencies of
      electric field gradients in cubic and hexagonal systems.
AB  - We present ab-initio calculations of the independent components of gradient
      elastic tensors, so-called gradient elastic constants, which relate electric
      field gradient tensors to stress or strain tensors. The constants of cubic and
      hexagonal metals, MAX phases, and zinc oxide were determined within the framework
      of density functional theory by using the augmented plane waves plus local
      orbitals method implemented in the WIEN2k code. Comparison with experimental
      gradient elastic constants and electric field gradients' stress dependencies
      suggest an accuracy of about 30% of the calculated constants, independent of the
      probe that detects the field gradient being self- or foreign-atom. Changes in the
      electric field gradient take place by strain-induced asymmetric occupations of
      the p and d states in the valence region for all investigated materials. Volume
      and structural dependencies of the electric field gradient can directly be
      determined from this fundamental approach and are, for hexagonal closed packed
      metals, consistent with vanishing electric field gradients around ideal close
      packing and volume dependencies larger than one. The concept of these
      calculations is applicable in any hyperfine interaction method and, thus, can be
      used to gain information about intrinsic strains in systems where the
      experimental gradient elastic constants are inaccessible. 

PMID- 25614687
TI  - Welcome reassurance about GLP-1 drugs--but they are still young and not fully
      grown.

PMID- 25614688
TI  - Innovative approaches to understanding and addressing health disparities in
      diabetes care and research.

PMID- 25614689
TI  - A review of the mental health issues of diabetes conference.
AB  - Individuals with type 1 diabetes are at increased risk for depression, anxiety
      disorder, and eating disorder diagnoses. People with type 1 diabetes are also at
      risk for subclinical levels of diabetes distress and anxiety. These
      mental/behavioral health comorbidities of diabetes are associated with poor
      adherence to treatment and poor glycemic control, thus increasing the risk for
      serious short- and long-term physical complications, which can result in
      blindness, amputations, stroke, cognitive decline, decreased quality of life, as
      well as premature death. When mental health comorbidities of diabetes are not
      diagnosed and treated, the financial cost to society and health care systems is
      catastrophic, and the human suffering that results is profound. This review
      summarizes state-of-the-art presentations and working group scholarly reports
      from the Mental Health Issues of Diabetes Conference (7-8 October 2013,
      Philadelphia, PA), which included stakeholders from the National Institutes of
      Health, people living with type 1 diabetes and their families, diabetes consumer
      advocacy groups, the insurance industry, as well as psychologists, psychiatrists,
      endocrinologists, and nurse practitioners who are all nationally and
      internationally recognized experts in type 1 diabetes research and care. At this
      landmark conference current evidence for the incidence and the consequences of
      mental health problems in type 1 diabetes was presented, supporting the
      integration of mental health screening and mental health care into routine
      diabetes medical care. Future research directions were recommended to establish
      the efficacy and cost-effectiveness of paradigms of diabetes care in which
      physical and mental health care are both priorities. 

PMID- 25614691
TI  - Elevated lactate levels in patients with poorly regulated type 1 diabetes and
      glycogenic hepatopathy: a new feature of Mauriac syndrome.

PMID- 25614692
TI  - Dietary phosphatidylcholine intake and type 2 diabetes in men and women.

PMID- 25614693
TI  - Treatment with the dipeptidyl peptidase-4 inhibitor linagliptin or placebo
      followed by glimepiride in patients with type 2 diabetes with moderate to severe
      renal impairment: a 52-week, randomized, double-blind clinical trial.

PMID- 25614694
TI  - Paging Dr. Google: parents' report of internet use for type 1 diabetes
      management.

PMID- 25614695
TI  - Insulin detemir does not cross the human placenta.

PMID- 25614696
TI  - Comment on Vimalananda et al. Depressive symptoms, antidepressant use, and the
      incidence of diabetes in the Black Women's Health Study. Diabetes Care
      2014;37:2211-2217.

PMID- 25614697
TI  - Response to Comment on Vimalananda et al. Depressive symptoms, antidepressant
      use, and the incidence of diabetes in the Black Women's Health Study. Diabetes
      Care 2014;37:2211-2217.

PMID- 25614698
TI  - Comment on Retnakaran et al. Liraglutide and the preservation of pancreatic beta
      cell function in early type 2 diabetes: the LIBRA trial. Diabetes Care
      2014;37:3270-3278.

PMID- 25614699
TI  - Response to Comment on Retnakaran et al. Liraglutide and the preservation of
      pancreatic beta-cell function in early type 2 diabetes: the LIBRA trial. Diabetes
      Care 2014;37:3270-3278.

PMID- 25614700
TI  - Comment on Stegman et al. High-intensity statin therapy alters the natural
      history of diabetic coronary atherosclerosis: insights from SATURN. Diabetes Care
      2014;37:3114-3120.

PMID- 25614701
TI  - Response to Comment on Stegman et al. High-intensity statin therapy alters the
      natural history of diabetic coronary atherosclerosis: insights from SATURN.
      Diabetes Care 2014;37:3114-3120.

PMID- 25614702
TI  - Comment on Pilz et al. Insulin sensitivity and albuminuria: the RISC study.
      Diabetes Care 2014;37:1597-1603.

PMID- 25614703
TI  - Response to Comment on Pilz et al. Insulin sensitivity and albuminuria: the RISC
      study. Diabetes Care 2014;37:1597-1603.

PMID- 25614705
TI  - Correction.

PMID- 25614706
TI  - Correction.

PMID- 25614704
TI  - In vitro and in vivo characterization of 13 CYP2C9 allelic variants found in
      Chinese Han population.
AB  - Our previous study detected totally 35 CYP2C9 allelic variants in 2127 Chinese
      subjects, of whom 21 novel alleles were reported for the first time in Chinese
      populations. The aim of the present study was to characterize the 13 CYP2C9
      allelic variants both in vitro and in vivo. Different types of CYP2C9 variants
      were highly expressed in COS-7 cells, and 50 MUM tolbutamide was added as the
      probing substrate to evaluate their metabolic abilities in vitro. Subsequently,
      the concentrations of tolbutamide and its metabolite in the plasma and urine
      within individuals with different types of genotypes were determined by HPLC to
      evaluate the catalytic activity of the 13 mutant CYP2C9 proteins in vivo. Our
      results showed that compared with *1/*1 wild-type subjects, subjects with *1/*40
      genotype showed increased oral clearance (CL/F), whereas individuals with *1/*3,
      *1/*13, *3/*3, *3/*13, *1/*16, *1/*19, *1/*34, *1/*42, *1/*45, *1/*46, and *1/*48
      genotype exhibited significantly decreased CL/F, and those with *1/*27, *1/*29,
      *1/*40, and *1/*41 genotype presented similar CL/F value. When expressed in COS-7
      cells, the CYP2C9 variants showed similar pattern to the results in clinical
      study. The study suggests that, besides two typical defective alleles, *3 and
      *13, seven CYP2C9 allelic variants (*16, *19, *34, *42, *45, *46, and *48) cause
      defective effects on the enzymatic activities both in vitro and in vivo. In
      clinic, patients with these defective alleles should be paid close attention to. 

PMID- 25614707
TI  - Teaching Word Identification to Students with Reading Difficulties and
      Disabilities.

PMID- 25614708
TI  - NMR Studies of Thermo-responsive Behavior of an Amphiphilic Poly(asparagine)
      Derivative in Water.
AB  - The thermo-responsive behavior of a unique biocompatible polymer, poly(N
      substituted alpha/beta-asparagine) derivative (PAD), has been studied with
      several NMR methods. The 1H and 13C solution NMR measurements of the PAD in DMSO
      d6 were used to investigate the isolated polymer and perform spectral
      assignments. By systematic addition of D2O we have tracked structural changes due
      to aggregation and observed contraction of hydrophilic side chains. Solution and
      cross polarization / magic angle spinning (CP/MAS) 13C NMR approaches were
      implemented to investigate the aggregates of the PAD aqueous solution during the
      liquid to gel transition as the temperature was increased. At temperatures near
      20  degrees C, all of the peaks from the PAD were observed in the 13C CP/MAS and
      13C solution NMR spectra, indicating the presence of polymer chain nodes.
      Increasing the temperature to 40  degrees C resulted in a partial disentanglement
      of the nodes due to thermal agitation and further heating resulted in little to
      no additional structural changes. Deuterium T1-T2 and T2-T2 two-dimensional
      relaxation spectroscopies using an inverse Laplace transform, were also
      implemented to monitor the water-PAD interaction during the phase transition. At
      temperatures near 20  degrees C the dynamical characteristics of water were
      manifested into one peak in the deuterium T1-T2 map. Increasing the temperature
      to 40  degrees C resulted in several distinguishable reservoirs of water with
      different dynamical characteristics. The observation of several reservoirs of
      water at the temperature of gel formation at 40  degrees C is consistent with a
      physical picture of a gel involving a network of interconnected polymer chains
      trapping a fluid. Further increase in temperature to 70  degrees C resulted in
      two non-exchanging water reservoirs probed by deuterium T2-T2 measurements.

PMID- 25614709
TI  - PSYCHOSOCIAL IMPLICATIONS OF STILLBIRTH FOR THE MOTHER AND HER FAMILY: A CRISIS
      SUPPORT APPROACH.

PMID- 25614710
TI  - Fluvastatin upregulates the alpha 1C subunit of CaV1.2 channel expression in
      vascular smooth muscle cells via RhoA and ERK/p38 MAPK pathways.
AB  - Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a hallmark of
      vascular disorders such as atherosclerosis and restenosis. And this process has
      been related to remodeling of L-type calcium channel (LTCC). We attempted to
      investigate whether fluvastatin has any effect on VSMC proliferation and
      LTCCalpha 1C subunit (LTCCalpha 1C) expression as well as the potential
      mechanisms involved. The VSMCs proliferation was assayed by osteopontin
      immunofluorescent staining and [(3)H]-thymidine incorporation. The cell cycle was
      detected by flow cytometric analysis. The activity of RhoA was determined with
      pull-down assay. MAPK activity and LTCCalpha 1C expression were assessed by
      western blotting. We demonstrated fluvastatin prevented the VSMCs
      dedifferentiating into a proliferative phenotype and induced cell cycle arrest in
      the G0/G1 phase in response to PDGF-BB stimulation. Fluvastatin dose-dependently
      reversed the downregulation of LTCCalpha 1C expression induced by PDGF-BB.
      Inhibition of ROCK, ERK, or p38 MAPK activation largely enhanced the upregulation
      effect of fluvastatin (P < 0.01). However, blockade of JNK pathway had no effect
      on LTCCalpha 1C expression. We concluded LTCCalpha 1C was a VSMC contractile
      phenotype marker gene. Fluvastatin upregulated LTCCalpha 1C expression, at least
      in part, by inhibiting ROCK, ERK1/2, and p38 MAPK activation. Fluvastatin may be
      a potential candidate for preventing or treating vascular diseases. 

PMID- 25614711
TI  - The academic effects of after-school paid and unpaid work among 14-year-old
      students in TIMSS countries.
AB  - What it means to be a 'student' varies within and between countries. Apart from
      the wide variety of school types and school quality that is experienced by young
      people, there also is, accompanying increased rates of school participation, a
      growing population of students who work part-time. The theoretical and actual
      consequences of student work have long been in dispute. This article reformulates
      the dispute as an empirical question that can be addressed using cross-national
      testing data and student background information from the Trends in International
      Math and Science Study (TIMSS). Drawing information from 20 countries with
      distinctive proportions of students who reported paid and unpaid work, this study
      first compares their academic achievement in each country. Next, regression
      analysis is used to control for students' home resources, and estimates are made
      of the effects of work and the differences in these effects cross-nationally.
      Finally, hierarchical linear models are estimated in each country so as to
      control for school effects, and to take into account the fact that working
      students may be clustered in lower-achieving schools. The results show that work
      after school, whether paid or unpaid, never positively affects academic
      achievement. However, after controlling for home resources and school effects,
      work negatively affects achievement only in certain countries. The article
      concludes with a discussion of the ways to interpret international differences in
      the effect of students' work.

PMID- 25614714
TI  - Quercetin protects against obesity-induced skeletal muscle inflammation and
      atrophy.
AB  - Skeletal muscle inflammation and atrophy are closely associated with metabolic
      impairment such as insulin resistance. Quercetin, a natural polyphenol flavonoid,
      is known to elicit anti-inflammatory and antioxidant activities. In this study,
      we investigated its effect on obesity-induced skeletal muscle inflammation and
      atrophy in mice. Male C57BL/6 mice were fed a regular diet, a high-fat diet
      (HFD), and an HFD supplemented with quercetin for nine weeks. Quercetin reduced
      levels of inflammatory cytokines and macrophage accumulation in the skeletal
      muscle of the HFD-fed obese mice. It also reduced transcript and protein levels
      of the specific atrophic factors, Atrogin-1 and MuRF1, in the skeletal muscle of
      the HFD-fed obese mice, and protected against the reduction of muscle mass and
      muscle fiber size. In vitro, quercetin markedly diminished transcript levels of
      inflammatory receptors and activation of their signaling molecules (ERK, p38
      MAPK, and NF-kappaB) in cocultured myotubes/macrophages, and this was accompanied
      by reduced expression of the atrophic factors. Together, these findings suggest
      that quercetin reduces obesity-induced skeletal muscle atrophy by inhibiting
      inflammatory receptors and their signaling pathway. Quercetin may be useful for
      preventing obesity-induced muscle inflammation and sarcopenia. 

PMID- 25614716
TI  - Luminal gastrointestinal surgery: what is round the corner?

PMID- 25614712
TI  - Neonatal sepsis and inflammatory mediators.
AB  - Neonatal sepsis is a major cause of morbidity and mortality and its signs and
      symptoms are nonspecific, which makes the diagnosis difficult. The routinely used
      laboratory tests are not effective methods of analysis, as they are extremely
      nonspecific and often cause inappropriate use of antibiotics. Sepsis is the
      result of an infection associated with a systemic inflammatory response with
      production and release of a wide range of inflammatory mediators. Cytokines are
      potent inflammatory mediators and their serum levels are increased during
      infections, so changes from other inflammatory effector molecules may occur.
      Although proinflammatory and anti-inflammatory cytokines have been identified as
      probable markers of neonatal infection, in order to characterize the inflammatory
      response during sepsis, it is necessary to analyze a panel of cytokines and not
      only the measurement of individual cytokines. Measurements of inflammatory
      mediators bring new options for diagnosing and following up neonatal sepsis, thus
      enabling early treatment and, as a result, increased neonatal survival. By taking
      into account the magnitude of neonatal sepsis, the aim of this review is to
      address the role of cytokines in the pathogenesis of neonatal sepsis and its
      value as a diagnostic criterion. 

PMID- 25614713
TI  - Role of cytokines and Toll-like receptors in the immunopathogenesis of Guillain
      Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune disease of the peripheral nervous
      system, mostly triggered by an aberrant immune response to an infectious
      pathogen. Although several infections have been implicated in the pathogenesis of
      GBS, not all such infected individuals develop this disease. Moreover, infection
      with a single agent might also lead to different subtypes of GBS emphasizing the
      role of host factors in the development of GBS. The host factors regulate a broad
      range of inflammatory processes that are involved in the pathogenesis of
      autoimmune diseases including GBS. Evidences suggest that systemically and
      locally released cytokines and their involvement in immune-mediated demyelination
      and axonal damage of peripheral nerves are important in the pathogenesis of GBS.
      Toll-like receptors (TLRs) link innate and adaptive immunity through
      transcription of several proinflammatory cytokines. TLR genes may increase
      susceptibility to microbial infections; an attenuated immune response towards
      antigen and downregulation of cytokines occurs due to mutation in the gene.
      Herein, we discuss the crucial role of host factors such as cytokines and TLRs
      that activate the immune response and are involved in the pathogenesis of the
      disease. 

PMID- 25614715
TI  - CD206+ cell number differentiates influenza A (H1N1)pdm09 from seasonal influenza
      A virus in fatal cases.
AB  - In 2009, a new influenza A (H1N1) virus affected many persons around the world.
      There is an urgent need for finding biomarkers to distinguish between influenza A
      (H1N1)pdm09 and seasonal influenza virus. We investigated these possible
      biomarkers in the lung of fatal cases of confirmed influenza A (H1N1)pdm09.
      Cytokines (inflammatory and anti-inflammatory) and cellular markers (macrophages
      and lymphocytes subpopulation markers) were analyzed in lung tissue from both
      influenza A (H1N1)pdm09 and seasonal influenza virus. High levels of IL-17, IFN
      gamma, and TNF-alpha positive cells were identical in lung tissue from the
      influenza A (H1N1)pdm09 and seasonal cases when compared with healthy lung tissue
      (P < 0.05). Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in
      high levels in both influenza A (H1N1)pdm09 and seasonal influenza virus (P <
      0.05). Low levels of CD206+ cells (marker of alternatively activated macrophages
      marker in lung) were found in influenza A (H1N1)pdm09 when compared with seasonal
      influenza virus (P < 0.05), and the ratio of CD206/CD14+ cells was 2.5-fold
      higher in seasonal and noninfluenza group compared with influenza A (H1N1)pdm09
      (P < 0.05). In conclusion, CD206+ cells differentiate between influenza A
      (H1N1)pdm09 and seasonal influenza virus in lung tissue of fatal cases. 

PMID- 25614717
TI  - Management of acute diverticulitis and its complications.
AB  - Colonic diverticular disease is a common condition, and around a quarter of
      people affected by it will experience acute symptoms at some time. The most
      common presentation is uncomplicated acute diverticulitis that can be managed
      conservatively with bowel rest and antibiotics. However, some patients will
      present with diverticular abscesses or purulent or faeculent peritonitis due to
      perforated diverticular disease. Whilst most mesocolic abscesses can be managed
      with percutaneous drainage alone, pelvic abscesses are associated with a higher
      rate of future complications and usually require percutaneous drainage followed
      by interval sigmoid resection. Patients who require emergency surgery for
      complicated acute diverticulitis most commonly undergo a Hartmann's procedure,
      although resection with primary anastomosis and laparoscopic peritoneal lavage
      have emerged as alternative treatment options for patients with purulent
      peritonitis in recent years. However, robust evidence from randomized trials is
      lacking for these alternative procedures, and the studies that have reported good
      outcomes from them have included carefully selected patient groups. There has
      been a move away from recommending elective prophylactic colectomy after two
      episodes of acute diverticulitis in the light of evidence that most patients will
      not experience a significant recurrence of their symptoms; elective surgery is
      indicated for those with ongoing symptoms, pelvic abscesses, complications-such
      as fistulating disease, strictures or recurrent diverticular bleeding-and those
      who are at high risk of perforation during future episodes, for example, due to
      immunosuppression, chronic renal failure or collagen-vascular diseases. 

PMID- 25614718
TI  - Laparoscopic Surgery in Luminal Gastrointestinal Emergencies-a Review of Current
      Status.
AB  - Laparoscopy has already established itself as the preferred surgical approach in
      a variety of elective surgical conditions. Along with its usual advantages of
      less tissue trauma and faster recovery, its diagnostic as well as therapeutic
      role is making it an attractive option in emergency surgery. In this paper, we
      have reviewed the current status of laparoscopic surgery in luminal
      gastrointestinal emergencies. Relevant papers were selected using Medline
      database from 2007 to the present. These were reviewed, and outcomes were stated
      under the headings of appendicitis, perforated peptic ulcer, colorectal
      emergencies and small bowel obstruction. The laparoscopic intervention was found
      to be of clear benefit in most of the patients with appendicitis. Its role,
      however, is not absolutely clear in managing perforated peptic ulcers.
      Laparoscopic lavage and drainage have been recommended in diverticular
      perforation with limited contamination. Small case series and studies have shown
      benefits of laparoscopic surgery in iatrogenic colonic perforations, colonic
      obstruction, emergency colectomy and small bowel obstruction. Laparoscopic
      surgery can be recommended in appendicitis and low-risk cases of perforated
      peptic ulcers. Its definitive role in other conditions needs more evidence. The
      surgeon's experience and careful patient selection are very important to improve
      the outcome. 

PMID- 25614720
TI  - Gastroesophageal reflux disease: diagnosis and patient selection.
AB  - Gastroesophageal reflux disease (GERD) has a high prevalence worldwide. Recent
      reports have noted a high prevalence even in Asian countries. GERD significantly
      affects the quality of life and can present with a wide variety of symptoms. Not
      all reflux is acid, and non-acid reflux disease can be more difficult to diagnose
      and can lead to a variety of extra-esophageal symptoms. Although proton pump
      inhibitors (PPIs) are effective in the majority of patients, but they are not
      without side effects, and their effect often diminishes with time. For patients
      who do not desire to be on long-term PPIs or have incomplete symptom resolution
      with medication, various endoscopic and minimally invasive treatment modalities
      are now available. The etiology of GERD can be multifactorial including
      dysfunctional LES, presence of a hiatal hernia, and transient lower esophageal
      sphincter relaxations (TLESRs). We hence believe that the treatment should be
      individualized to the cause of the reflux. In the following review, we describe
      the etiology of reflux disease and attempt to lay a framework for the diagnosis
      and selection of patients for the various interventions available for treatment,
      along with their evidence base. 

PMID- 25614719
TI  - Is Laparoscopic Surgery the Standard of Care for GI Luminal Cancer?
AB  - As surgeons in India strive to keep pace with the technical advances in the field
      of laparoscopic surgery, we endeavor to evaluate the mounting global evidence
      regarding laparoscopic gastric and colorectal resections for cancer. We seem to
      be riding on the crest of excellence in traditional open surgery for
      gastrointestinal malignancies, opening avenues for research and for the
      establishment of practice guidelines in laparoscopic surgery. Results from
      available trials along with those from ongoing studies are paving the path toward
      the acceptance and standardization of these procedures. What must be ascertained
      is whether sound oncological principles, which are ultimately exhibited by long
      term outcomes, are being preserved while garnering the established benefits of
      minimally invasive surgery. 

PMID- 25614721
TI  - Laparoscopic Rectopexy for Rectal Prolapse: Will it be the Gold Standard?
AB  - A review of the current literature is presented regarding the surgical management
      of full thickness rectal prolapse, comparing laparoscopic rectopexy with open
      abdominal operations and perineal procedures. Outcome measures include length of
      stay, short- and long-term outcomes and financial burdens. Current evidence
      suggests that laparoscopic rectopexy as treatment for full thickness rectal
      prolapse is a safe alternative to the other options. 

PMID- 25614722
TI  - Informed decision-making for bariatric surgery: benefits, risks, uncertainties
      and choices.
AB  - Decision-making is a critical aspect of good surgical care, and this principle is
      particularly important in bariatric surgery. Adequate communication of
      information to patients is essential in order to facilitate optimal uptake of
      bariatric surgery and choice of the most suitable procedure. This article reviews
      the most relevant advances in understanding of long-term efficacy associated with
      gastric banding, gastric bypass and sleeve gastrectomy. 

PMID- 25614723
TI  - Paradigm shift in the management of rectal cancer.
AB  - Surgery for rectal cancer in the pre-Total Mesorectal Excision (TME) era was
      associated with high local recurrence rates. The widespread adoption of the TME
      technique together with the addition of neoadjuvant oncological therapies have
      reduced local failure rates and improved survival for patients with rectal
      cancer. Advances in our knowledge, better understanding of tumour biology and
      refinement in minimal access techniques and equipment have significantly changed
      the management of rectal cancer. This paper reviews these changes and proposes a
      paradigm shift in how rectal cancer management is conceptualised and treated,
      such that the treatment of rectal cancer is separated into early tumours
      (potentially suitable for local excison), TME tumours (optimally managed by TME)
      and beyond TME tumours (optimally managed by multivisceral resection outside the
      TME plane). 

PMID- 25614724
TI  - Management of Fistula-in-Ano-The Current Evidence.
AB  - Successful treatment for fistula in ano has eluded most surgeons. To choose the
      right surgery has been made more difficult, with new surgeries being added in the
      last decade. This article discusses the various accepted surgeries for fistula in
      ano - their pros & cons, & attempts to provide the status of the various
      procedures as it stands today. 

PMID- 25614725
TI  - E learning in surgery.
AB  - E learning means use of electronic media and information technologies in
      education. Virtual learning environment (VLE) provides learning platforms
      consisting of online tools, databases and managed resources. This article is a
      review of use of E learning in medical and surgical education including available
      evidence favouring this approach. E learning has been shown to be more effective,
      less costly and more satisfying to the students than the traditional methods. E
      learning cannot however replace direct consultant supervision at their place of
      work in surgical trainees and a combination of both called blended learning has
      been shown to be most useful. As an example of university-based qualification,
      one such programme is presented to clarify the components and the process of E
      learning. Increasing use of E learning and occasional face to face focussed
      supervision by the teacher is likely to enhance surgical training in the future. 

PMID- 25614727
TI  - Contributors to Intelligibility in Preschool- Aged Children with Cerebral Palsy.
AB  - PURPOSE: We investigated the contribution of vowel space, articulation rate,
      maximum utterance length, and language skills to intelligibility in 30-36 month
      old children with CP. We also examined differences among variables for 3
      subgroups of children with CP and a small group of typically developing (TD)
      children. METHOD: Nineteen children with CP and 5 TD children provided speech
      samples, and 120 listeners transcribed the speech samples. Acoustic analysis of
      temporal and vowel spectral measures was completed on single-word productions.
      RESULTS: Vowel space was the only variable that made a significant and
      independent contribution to intelligibility, though all variables collectively
      accounted for 74% of the variance in intelligibility scores. TD children tended
      to have larger vowel spaces, than children with CP, even among children with CP
      who had intelligibility scores within the range of TD children. CONCLUSIONS: Of
      children with CP who were able to talk at 30-36 months of age, 60% had clinical
      speech or language deficits. Production of vowels appears to make an important
      contribution to intelligibility; and for many children with CP, considerable
      deficits in intelligibility may be evident by the age of 3. Early interventions
      targeting both speech and language may improve intelligibility and functional
      communication skills.

PMID- 25614726
TI  - Multimodality management of esophageal cancer.
AB  - Esophageal cancer is a morbid disease with a grim prognosis. The outcomes of
      treatment even in non-metastatic disease undergoing potentially curative surgery
      are poor with 5-year survival ranging from 20 to 35 %. Several multimodality
      treatment options have been investigated in well-conducted randomised trials and
      meta-analyses evaluating both neoadjuvant and adjuvant therapies. However, there
      is still lack of uniform practice in the management of operable esophageal
      cancer. We review the current evidence for multimodality treatment of esophageal
      cancer, critically analysing the evidence supporting the use of each strategy,
      the pros and cons of each approach and discuss our approach in management.
      Neoadjuvant chemotherapy or chemoradiotherapy are currently the standard of care
      in localised esophageal cancer. 

PMID- 25614728
TI  - Relationship Between Prosody and Intelligibility in Children with Dysarthria.
AB  - Exaggerated and redundant prosodic cue use has been noted among adults with
      dysarthria secondary to cerebral palsy (CP) (Patel, 2004; van Doorn & Sheard,
      2001). A possible explanation may be that speakers heighten prosodic contrasts to
      increase intelligibility. The current work examined whether children with
      dysarthria due to CP also produce exaggerated prosodic contours and if so, how
      prosodic cue use in these speakers impacts intelligibility. Acoustic analyses
      were conducted on a previously collected dataset of 2-7 word utterances produced
      by fourteen children with CP (7 with dysarthria and 7 without) (Hustad, Gorton &
      Lee, 2010). The dataset also included sentence-level transcriptions obtained from
      five listeners per speaker. Word intelligibility scores were derived from these
      transcripts and used to determine whether prosodic modulation differed for words
      with high versus low intelligibility. Although mean fundamental frequency (F0)
      and intensity range were similar across groups, words produced by children with
      dysarthria were slower and more variable in F0 than the group without dysarthria.
      Moreover, intelligibility decreased when children with dysarthria increased F0
      and duration beyond the range used by children without dysarthria. Thus findings
      suggest that interventions targeting appropriate prosody may be beneficial in
      improving intelligibility in children with dysarthria and CP.

PMID- 25614729
TI  - Increased prevalence of colorectal polyp in acromegaly patients: a case-control
      study.
AB  - An increase in the prevalence of colorectal polyps and cancer is reported in
      patients with acromegaly. This trial is designed to determine whether there is an
      increase in the prevalence of colorectal polyps/cancer in Turkish acromegaly
      patients. Sixty-six patients, who were under follow-up with the diagnosis of
      acromegaly and underwent total colonoscopic examination, were enrolled in the
      study. Sixty-five age- and gender-matched patients with nonspecific complaints
      were selected as control. The mean age of acromegalic patients was 51.5 +/- 12.8
      years of whom 27 (40.9%) were females. In 20 (30.3%) of the patients with
      acromegaly a total of 65 colorectal polyps were detected. Forty-seven (72.3%) of
      the polyps were detected at the rectosigmoid region. In 8 (12.3%) of the 65
      control patients a total of 17 polyps were found. There was a statistically
      significant difference between the groups (P = 0.018). At the logistic regression
      analysis we found that the risk for colon polyps increased 3.2-fold in the
      presence of acromegaly, irrespective of age and gender (OR: 3.191, 95% CI: 1.25
      8.13). In conclusion, patients who were followed up with the diagnosis of
      acromegaly should be taken to the colonoscopic surveillance program and all
      polyps detected should be excised in order to protect them from colorectal
      cancer. 

PMID- 25614730
TI  - Eliminating Bias in Classify-Analyze Approaches for Latent Class Analysis.
AB  - Despite recent methodological advances in latent class analysis (LCA) and a rapid
      increase in its application in behavioral research, complex research questions
      that include latent class variables often must be addressed by classifying
      individuals into latent classes and treating class membership as known in a
      subsequent analysis. Traditional approaches to classifying individuals based on
      posterior probabilities are known to produce attenuated estimates in the analytic
      model. We propose the use of a more inclusive LCA to generate posterior
      probabilities; this LCA includes additional variables present in the analytic
      model. A motivating empirical demonstration is presented, followed by a
      simulation study to assess the performance of the proposed strategy. Results show
      that with sufficient measurement quality or sample size, the proposed strategy
      reduces or eliminates bias.

PMID- 25614731
TI  - Involvement with Children and Low-Income Fathers' Psychological Well-Being.
AB  - Low income men are at risk for depressive symptoms and reduced father
      involvement. Using the Fragile Families and Child Wellbeing Study (n = 2,703), we
      examined reciprocal associations between father involvement and depressive
      symptoms, and the moderating effect of relationship quality, for resident and
      nonresident fathers. Higher father involvement was associated with lower
      depressive symptoms two years later across the full sample of fathers. However,
      nonresidence functioned as a risk; higher nonresident father involvement with
      toddlers was associated with greater depressive symptoms two years later. Greater
      resident father involvement with toddlers was associated with fewer depressive
      symptoms two years later in low quality couple relationships. Across the full
      sample, the association between depressive symptoms and lower involvement was
      weak.

PMID- 25614732
TI  - Nuclear Receptor Signaling: a home for nuclear receptor and coregulator signaling
      research.
AB  - The field of nuclear receptor and coregulator signaling has grown into one of the
      most active and interdisciplinary in eukaryotic biology. Papers in this field are
      spread widely across a vast number of journals, which complicates the task of
      investigators in keeping current with the literature in the field. In 2003, we
      launched Nuclear Receptor Signaling as an Open Access reviews, perspectives and
      methods journal for the nuclear receptor signaling field. Building on its success
      and impact on the community, we have added primary research and dataset articles
      to this list of article categories, and we now announce the re-launch of the
      journal this month. Here we will summarize the rationale that informed the
      creation and expansion of the journal, and discuss the possibilities for its
      future development. 

PMID- 25614733
TI  - DNA Binding Test, X-Ray Crystal Structure, Spectral Studies, TG-DTA, and
      Electrochemistry of [CoX 2 (dmdphphen)] (Dmdphphen Is 2,9-Dimethyl-4,7-diphenyl
      1,10-phenanthroline, X = Cl, and NCS) Complexes.
AB  - Two new neutral mixed-ligand cobalt(II) complexes, [CoCl2(dmdphphen)] 1 and
      [Co(NCS)2(dmdphphen)]  2, where dmdphphen is 2,9-dimethyl-4,7-diphenyl-1,10
      phenanthroline, were synthesized and characterized by an elemental analysis, UV
      Vis, IR, TG/DTA, cyclic voltammetry CV, and single X-ray diffraction. Complex 2
      crystallized as monoclinic with a space group P21/c. Co(II) ions are located in a
      distorted tetrahedral environment. TG/DTA result shows that these complexes are
      very stable and decomposed through one-step reaction. The two complexes exhibit a
      quasireversible one-electron response at -550 and 580 mV versus Cp2Fe/Cp2Fe(+),
      which has been assigned to Co(I)/Co(II) and Co(II)/Co(III) couples. Absorption
      spectral studies reveal that such complexes exhibit hypochromicity during their
      interaction with CT-DNA. 

PMID- 25614734
TI  - PGC1alpha -1 Nucleosome Position and Splice Variant Expression and Cardiovascular
      Disease Risk in Overweight and Obese Individuals.
AB  - PGC1alpha, a transcriptional coactivator, interacts with PPARs and others to
      regulate skeletal muscle metabolism. PGC1alpha undergoes splicing to produce
      several mRNA variants, with the NTPGC1alpha variant having a similar biological
      function to the full length PGC1alpha (FLPGC1alpha). CVD is associated with
      obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired
      mitochondrial function in skeletal muscle, characteristics determined by
      PGC1alpha expression. PGC1alpha expression is epigenetically regulated in
      skeletal muscle to determine mitochondrial adaptations, and epigenetic
      modifications may regulate mRNA splicing. We report in this paper that skeletal
      muscle PGC1alpha  -1 nucleosome (-1N) position is associated with splice variant
      NTPGC1alpha but not FLPGC1alpha expression. Division of participants based on the
      -1N position revealed that those individuals with a -1N phased further upstream
      from the transcriptional start site (UP) expressed lower levels of NTPGC1alpha
      than those with the -1N more proximal to TSS (DN). UP showed an increase in body
      fat percentage and serum total and LDL cholesterol. These findings suggest that
      the -1N may be a potential epigenetic regulator of NTPGC1alpha splice variant
      expression, and -1N position and NTPGC1alpha variant expression in skeletal
      muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov,
      identifier NCT00458133. 

PMID- 25614735
TI  - Sporotrichosis: an overview and therapeutic options.
AB  - Sporotrichosis is a chronic granulomatous mycotic infection caused by Sporothrix
      schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss,
      that is endemic in tropical/subtropical areas. The recent phylogenetic studies
      have delineated the geographic distribution of multiple distinct Sporothrix
      species causing sporotrichosis. It characteristically involves the skin and
      subcutaneous tissue following traumatic inoculation of the pathogen. After a
      variable incubation period, progressively enlarging papulo-nodule at the
      inoculation site develops that may ulcerate (fixed cutaneous sporotrichosis) or
      multiple nodules appear proximally along lymphatics (lymphocutaneous
      sporotrichosis). Osteoarticular sporotrichosis or primary pulmonary
      sporotrichosis are rare and occur from direct inoculation or inhalation of
      conidia, respectively. Disseminated cutaneous sporotrichosis or involvement of
      multiple visceral organs, particularly the central nervous system, occurs most
      commonly in persons with immunosuppression. Saturated solution of potassium
      iodide remains a first line treatment choice for uncomplicated cutaneous
      sporotrichosis in resource poor countries but itraconazole is currently
      used/recommended for the treatment of all forms of sporotrichosis. Terbinafine
      has been observed to be effective in the treatment of cutaneous sporotrichosis.
      Amphotericin B is used initially for the treatment of severe, systemic disease,
      during pregnancy and in immunosuppressed patients until recovery, then followed
      by itraconazole for the rest of the therapy. 

PMID- 25614737
TI  - Influence of DPYD Genetic Polymorphisms on 5-Fluorouracil Toxicities in Patients
      with Colorectal Cancer: A Meta-Analysis.
AB  - Our meta-analysis aggregated existing results from relevant studies to
      comprehensively investigate the correlations between genetic polymorphisms in
      dihydropyrimidine dehydrogenase (DPYD) gene and 5-fluorouracil (5-FU) toxicities
      in patients with colorectal cancer (CRC). The MEDLINE (1966~2013), the Cochrane
      Library Database (Issue 12, 2013), EMBASE (1980~2013), CINAHL (1982~2013), Web of
      Science (1945~2013), and the Chinese Biomedical Database (CBM) (1982~2013) were
      searched without language restrictions. Meta-analyses were conducted with the use
      of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA).
      Seven clinical cohort studies with a total of 946 CRC patients met our inclusion
      criteria, and NOS scores of each of the included studies were >=5. Our findings
      showed that DPYD genetic polymorphisms were significantly correlated with high
      incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis
      indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and
      2194G>A polymorphisms with the incidence of marrow suppression in CRC patients
      receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and
      2194G>A polymorphisms were correlated with the incidence of gastrointestinal
      reaction. Ethnicity-stratified analysis also revealed that DPYD genetic
      polymorphisms might contribute to the development of marrow suppression and
      gastrointestinal reaction among Asians, but not among Caucasians. The present
      meta-analysis suggests that DPYD genetic polymorphisms may be correlated with the
      incidence of 5-FU-related toxicity in CRC patients. 

PMID- 25614736
TI  - Colorectal cancer and basement membranes: clinicopathological correlations.
AB  - Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and
      the second in females. In 2008, an estimated 1.2 million people were diagnosed
      with and 608,700 people died of CRC. Besides diagnosis and treatment, prognosis
      is an important matter for cancer patients. Today, clinicopathological
      correlations have many applications in cancer prognostication. Examples include
      the prediction of the medium patient survival and the screening for patients
      suitable for specific therapeutic approaches. Apart from traditional prognostic
      factors, such as tumor stage and grade, new markers may be useful in clinical
      practice. Possible markers may result from the study of basement membranes (BMs).
      BM seems to play a role in the pathogenesis of colorectal cancer, so BM
      alterations may have prognostic significance as well. The purpose of this review
      is to briefly describe BMs and their relationship with CRC, in the aspect of
      clinicopathological correlations. 

PMID- 25614738
TI  - Lubiprostone decreases the small bowel transit time by capsule endoscopy: an
      exploratory, randomised, double-blind, placebo-controlled 3-way crossover study.
AB  - The aim of this study was to investigate the usefulness of lubiprostone for bowel
      preparation and as a propulsive agent in small bowel endoscopy. Six healthy male
      volunteers participated in this randomized, 3-way crossover study. The subjects
      received a 24 MUg tablet of lubiprostone 60 minutes prior to the capsule
      ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the
      capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24
      MUg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo
      tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE
      (P-P regimen). The quality of the capsule endoscopic images and the amount of
      water in the small bowel were assessed on 5-point scale. The median SBTT was
      178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P
      regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study
      showed that the use of lubiprostone significantly decreased the SBTT. We also
      confirmed that lubiprostone was effective for inducing water secretion into the
      small bowel during CE. 

PMID- 25614739
TI  - Flow Injection Photosensitized Chemiluminescence of Luminol with Cu(II)-Rose
      Bengal: Mechanistic Approach and Vitamin A and C Determination.
AB  - Rose Bengal photosensitized flow injection chemiluminescence method is reported
      using luminol-Cu(II) for the determination of vitamins A and C in pharmaceutical
      formulations. The reaction is based on the enhancement effect of analyte in the
      production of anion radicals of Rose Bengal (RB (*-)) which rapidly interact with
      dissolved oxygen and generate superoxide anions radicals (O2 (*-)) and hydrogen
      peroxide (H2O2). Highly reactive hydroxyl radicals ( (*) OH) were produced via
      dismutation of H2O2 by catalyst (Cu(2+)). The generated superoxide anions
      radicals and hydroxyl radicals thus oxidize luminol in alkaline medium to
      generate strong chemiluminescence. The limit of detection (3s of the blank, n =
      6) of vitamins A and C and RB was found to be 0.008, 0.005, and 0.05 MUg mL(-1),
      respectively. The sample throughput of 70 h(-1) for vitamins A and C and 30 h(-1)
      for RB was found. Calibration curve was linear in the range of 0.05-15, 0.01-20,
      and 0.1-50 MUg mL(-1) for vitamins A and C and RB, respectively, with relative
      standard deviations (RSDs; n = 3) in the range 1.6-3.6%. The method was
      successfully applied to pharmaceutical formulations and the results obtained were
      in good agreement with the labeled values. 

PMID- 25614740
TI  - Determination of Urinary Creatinine in Washington State Residents via Liquid
      Chromatography/Tandem Mass Spectrometry.
AB  - A viable, quick, and reliable method for determining urinary creatinine by liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) was developed and used to
      evaluate spot urine samples collected for the Washington Environmental
      Biomonitoring Survey (WEBS): part of the Washington State Department of Health,
      Public Health Laboratories (PHL). 50 uL of urine was mixed with a 1 : 1
      acetonitrile/water solution containing deuterated creatinine as the internal
      standard and then analyzed by LC/MS/MS. Utilizing electrospray ionization (ESI)
      in positive mode, the transition ions for creatinine and creatinine-d3 were
      determined to be 114.0 to 44.1 (quantifier), 114.0 to 86.1 (qualifier), and 117.0
      to 47.1 (creatinine-d3). The retention time for creatinine was 0.85 minutes. The
      linear calibration range was 20-4000 mg/L, with a limit of detection at 1.77 mg/L
      and a limit of quantitation at 5.91 mg/L. LC/MS/MS and the colorimetric Jaffe
      reaction were associated significantly (Pearson r = 0.9898 and R (2) = 0.9797,
      rho <= 0.0001). The LC/MS/MS method developed at the PHL to determine creatinine
      in the spot urine samples had shorter retention times, and was more sensitive,
      reliable, reproducible, and safer than other LC/MS/MS or commercial methods such
      as the Jaffe reaction or modified versions thereof. 

PMID- 25614741
TI  - The Development and Application of Novel IR and NMR-Based Model for the
      Evaluation of Carminative Effect of Artemisia judaica L. Essential Oil.
AB  - Artemisia judaica L. is a medicinal plant that is traditionally used to relieve
      abdominal pains through its carminative activity. In this study, spectroscopic
      analysis was employed to investigate the carminative activity associated with A.
      judaica. Using infrared spectroscopy, the carminative activity was evaluated
      based on the first derivative of IR-characteristic stretching signal of CO2. Our
      results indicate that A. judaica oil effectively reduced the response of CO2
      signal equivalent to thymol standard. Additionally, (1)H-NMR spectroscopy was
      utilized to assess surface activity of A. judaica crude oil through the reduction
      of interfacial tension in a D2O/CDCl3 system. Apparently, 10 mg of the oil was
      able to solubilize water in a chloroform layer up to 4.3% (w/w). In order to
      correlate the observed surface activity of the oil to its actual composition, GC
      MS and GC-FID structural analysis were undertaken. The results revealed that the
      oil composition consists of oxygenated terpenes which might be responsible for
      the carminative effect. Furthermore, owing to its sensitivity, our model provides
      a fundamental basis for the pharmacological assessment of trace amounts of oils
      with high precision and accuracy. 

PMID- 25614742
TI  - Effect of serum and oxygen concentration on gene expression and secretion of
      paracrine factors by mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) secrete paracrine factors that may exert a
      protective effect on the heart after coronary artery occlusion. This study was
      done to determine the effect of hypoxia and serum levels on the mRNA expression
      and secretion of paracrine factors. Mouse bone marrow MSC were cultured with 5%
      or 20% serum and in either normoxic (21% O2) or hypoxic (1% O2) conditions.
      Expression of mRNA for vascular endothelial growth factor (VEGF), monocyte
      chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP
      1alpha), MIP-1beta, and matrix metalloproteinase-2 (MMP-2) was determined by RT
      qPCR. Secretion into the culture media was determined by ELISA. Hypoxia caused a
      reduction in gene expression for MCP-1 and an increase for VEGF (5% serum), MIP
      1alpha, MIP-1beta, and MMP-2. Serum reduction lowered gene expression for VEGF
      (normoxia), MCP-1 (hypoxia), MIP-1alpha (hypoxia), MIP-1beta (hypoxia), and MMP-2
      (hypoxia) and increased gene expression for MMP-2 (normoxia). The level of
      secretion of these factors into the media generally paralleled gene expression
      with some exceptions. These data demonstrate that serum and oxygen levels have a
      significant effect on the gene expression and secretion of paracrine factors by
      MSC which will affect how MSC interact in vivo during myocardial ischemia. 

PMID- 25614743
TI  - Ewing sarcoma of the posterior fossa in an adolescent girl.
AB  - Medulloblastoma, astrocytoma, and ependymoma represent the most common
      infratentorial tumors in childhood, while Ewing sarcomas in that localization are
      extremely rare. A large left infratentorial space-occupying lesion was diagnosed
      in a 12-year-old girl with signs of increased intracranial pressure. Following
      total tumor resection, histological and molecular examination revealed Ewing
      sarcoma with rearranged EWSR-1 gene. The patient achieved complete remission
      following adjuvant chemotherapy and radiotherapy according to Euro-EWING 2008
      treatment protocol. Intracranial Ewing sarcoma, although rare, should be an
      important differential diagnosis of intracranial tumors in childhood which
      requires aggressive multimodal treatment. 

PMID- 25614744
TI  - Polymicrobial Bacteremia Involving Comamonas testosteroni.
AB  - Comamonas spp. are uncommon isolates in microbiology laboratories and have been
      rarely observed as an infectious agent in clinical practice. They have widespread
      environmental distribution and have been isolated from water, soil, and plants as
      well as from some hospital devices such as intravenous catheters and water
      contained in humidifier reservoirs used in respiratory treatment. The genus
      Comamonas originally contained the following species: acidovorans, testosteroni,
      kerstersii, terrigena, denitrificans, and nitrativorans. It now contains 17
      species, while acidovorans spp. have been reclassified as Delftia acidovorans. In
      spite of its uncommon human pathogenesis, there are few reports on the aggressive
      manner of it as an opportunistic pathogen, mostly related to testosteroni spp. We
      present a case of polymicrobial bacteremia involving Comamonas testosteroni. The
      aim of this case report is to alert clinicians to the potential diagnosis of
      bloodstream infections caused by uncommon pathogens. 

PMID- 25614745
TI  - Thiamine deficiency in self-induced refeeding syndrome, an undetected and
      potentially lethal condition.
AB  - Rapid restoration of nutrients and electrolytes after prolonged starvation could
      result in a life threatening condition characterized by sensory and neurological
      dysfunction and severe metabolic imbalance that has been designated as refeeding
      syndrome. Its diagnosis is frequently missed resulting in severe complications
      and even death. We describe a 25-years-old female patient with mental disorders
      and severe malnutrition who developed severe clinical manifestations and
      biochemical abnormalities characteristic of the refeeding syndrome, after
      restarting oral feeding on her own. Schizophrenia was later diagnosed. Increased
      awareness of this condition and its complications is necessary to prevent its
      detrimental complications. 

PMID- 25614746
TI  - Cor triatriatum sinister identified after new onset atrial fibrillation in an
      elderly man.
AB  - A 73-year-old man with new onset atrial fibrillation with rapid ventricular
      response underwent transthoracic echocardiography that revealed an echogenic
      linear structure along the left atrium, suggestive of cor triatriatum sinister
      (CTS). CTS was confirmed with transesophageal echocardiography which demonstrated
      a proximal accessory atrium receiving pulmonary venous flow separated from a
      distal true atrium by a fibromuscular membrane with a large fenestration allowing
      flow between the chambers. In CTS, the left atrium is divided into proximal and
      distal chambers by a fenestrated fibromuscular septum. This cardiac anomaly
      accounts for 0.1% of cases of congenital heart disease and rarely presents in
      adults. CTS is primarily diagnosed with echocardiography and is associated with
      left atrial enlargement and development of atrial fibrillation. Treatment options
      depend on size of the communication between proximal and distal chambers, the
      gradient across the membrane, and the position of pulmonary veins. In some
      instances, surgical resection of the membrane that divides the left atrium is
      warranted. 

PMID- 25614747
TI  - Abnormal blood glucose as a prognostic factor for adverse clinical outcome in
      children admitted to the paediatric emergency unit at komfo anokye teaching
      hospital, kumasi, ghana.
AB  - Dysglycaemia (hyper- or hypoglycaemia) in critically ill children has been
      associated with poor outcome. We compared the clinical outcomes in children
      admitted to Pediatric Emergency Unit (PEU) at Komfo Anokye Teaching Hospital
      (KATH) for acute medical conditions and presenting with euglycaemia or
      dysglycaemia. This is a prospective case matching cohort study. Eight hundred
      subjects aged between 3 and 144 months were screened out of whom 430 (215 with
      euglycaemia and 215 with dysglycaemia) were enrolled. The median age was 24
      months (range: 3-144 months). In the dysglycaemia group, 28 (13%) subjects had
      hypoglycemia and 187 (87%) had hyperglycemia. Overall, there were 128
      complications in 116 subjects. The number of subjects with complications was
      significantly higher in dysglycaemia group (n = 99, 46%) compared to euglycaemia
      group (n = 17, 8%) (P < 0.001). Forty subjects died out of whom 30 had
      dysglycaemia (P = 0.001). Subjects with dysglycaemia were 3 times (95% CI: 1.5
      6.0) more likely to die and 4.8 times (95% CI: 3.1-7.5) more likely to develop
      complications (P = 0.001). Dysglycaemia is associated with increased morbidity
      and mortality in children with acute medical conditions and should lead to
      intensive management of the underlying condition. 

PMID- 25614748
TI  - Spiritual healing in the treatment of rheumatoid arthritis: an exploratory single
      centre, parallel-group, double-blind, three-arm, randomised, sham-controlled
      trial.
AB  - Our objective was to investigate the efficacy of "energy/spiritual healing" in
      rheumatoid arthritis (RA). Eligible patients were women with RA on stable
      medication. The design was a randomised, blinded, sham-controlled trial; the
      third group included an external unblinded control of the natural course of RA.
      Participants in both groups received 8 sessions with "perceived healing" over 21
      weeks with 8 weeks of follow-up. Active healing (AH) treatment comprised healing
      with no physical contact, and sham healing (SH) included exactly the same healing
      with a sham healer. During intervention, participants wore hearing protectors and
      were blindfolded. No healing (NH) only had their outcomes assessed. Coprimary
      outcomes were disease activity score (DAS) for 28 joints and Doppler ultrasound.
      All 96 patients randomised were handled as the intention-to-treat population,
      using a baseline-carried forward approach to replace the missing data. Eighty-two
      (85%) participants completed the 29-week trial. At end point (week 29), mean
      difference in DAS28 between AH versus SH was statistically but not clinically
      significant in favour of AH (0.62 DAS28 points; 95% CI: 0.13 to 1.11; P = 0.014),
      while no differences between groups occurred in Doppler ultrasound. There are no
      clear physiological or psychological explanations for the findings in this
      tightly controlled study. The trial data indicates a need for independent
      replication. 

PMID- 25614749
TI  - Traditional chinese medicine tongxinluo improves cardiac function of rats with
      dilated cardiomyopathy.
AB  - The study aimed at testing the hypothesis that tongxinluo capsule might exert its
      cardioprotective effect by preventing ventricular remodeling and improving
      coronary microvascular function in a rat model of doxorubicin-induced dilated
      cardiomyopathy (DCM). Rats that survived DCM induction were randomly divided into
      three groups to be given 1.5 g.kg(-1).day(-1) (TXL-H, n = 9) or 0.15 g.kg(
      1).day(-1) (TXL-L, n = 10) of tongxinluo, or normal saline at the same volume
      (DCM-C, n = 10) intragastrically. Age matched normal rats treated with normal
      saline were used as normal controls (NOR-C, n = 9). After four weeks of
      treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac
      dysfunction, left ventricular remodeling, and coronary microvascular dysfunction,
      compared with the NOR-C rats. However, myocardial functional parameters were
      significantly improved and microvascular density (MVD) increased in the TXL-H
      group compared with the DCM-C group (all P < 0.01). Left ventricular remodeling
      was prevented. There were close linear relationships between CVF and LVEF (r = 
      0.683, P < 0.05), MVD and LVEF (r = 0.895, P < 0.05), and MVD and CVF (r = 
      0.798, P < 0.05). It was indicated that high-dose tongxinluo effectively improved
      cardiac function in rat model of DCM. 

PMID- 25614750
TI  - Gastrodiae Rhizoma Ethanol Extract Enhances Pentobarbital-Induced Sleeping
      Behaviors and Rapid Eye Movement Sleep via the Activation of GABA A -ergic
      Transmission in Rodents.
AB  - This research was designed to identify whether Gastrodiae Rhizoma ethanol extract
      (GREE) enhances pentobarbital-induced sleep via  gamma-aminobutyric acid- (GABA-)
      ergic systems and modulated sleep architectures in animals. GREE (25, 50, and 100
      mg/kg, p.o.) inhibited locomotor activity in mice, in a dose-dependent manner.
      GREE not only prolonged total sleep time, but also reduced sleep latency time in
      pentobarbital (42 mg/kg)-treated mice. Subhypnotic pentobarbital (28 mg/kg, i.p.)
      also increased the number of total sleeping animals in concomitant administration
      of GREE. GREE (100 mg/kg) alone reduced the count of sleep-wake cycles in
      electroencephalogram. Furthermore, GREE increased total sleep time and rapid eye
      movement (REM) sleep. From the in vitro experiments, GREE increased intracellular
      chloride level in primary cultured cerebellar granule cells. Protein expressions
      of glutamine acid decarboxylase (GAD) and GABAA receptors subtypes by western
      blot were increased. Therefore, our study suggested that GREE enhances
      pentobarbital-induced sleeping behaviors and increased REM via the activation of
      GABAA-ergic transmission in rodents. 

PMID- 25614751
TI  - Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats.
AB  - This study evaluated the in vivo potential antihypertensive effect of
      hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar
      rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect
      on the vascular reactivity of resistance arteries. The hypotensive effect caused
      by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was
      dose-dependent and was partially inhibited by pretreatment with atropine sulfate.
      SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure,
      heart rate, and vascular reactivity were evaluated. Daily oral administration of
      HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum
      reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings
      the treatment with HESC reduced by 40% the maximum effect (E max?) of contraction
      induced by NE. The contractile response to calcium and NE of endothelium-deprived
      mesenteric rings isolated from untreated SHR was reduced in a concentration
      dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that
      Syzygium cumini reduces the blood pressure and heart rate of SHR and that this
      antihypertensive effect is probably due to the inhibition of arterial tone and
      extracellular calcium influx. 

PMID- 25614753
TI  - Ethiopathogenesis of depressive disorders.
AB  - Etiology of depressive disorders is still unknown. Several factors are involved
      in its pathophysiology such as neurotransmitters and neuroendocrine alterations,
      genetics, life events and their appraisal. Some of these components are strictly
      linked. Subjects with a family member affected by mood disorders are more prone
      to suffer from depressive disorders. It is also true that receiving feedbacks of
      indifference or neglect during childhood from one parent who suffer from
      depression may represent a factor of vulnerability. Indeed, reaction to a
      specific negative event may determine an increased allostasis which lead to a
      depressive episode. Thus, a psychological cause does not exclude a
      neurobiological cascade. Whereas in other cases recurrent depressive episodes
      appear in absence of any negative life event. This review provides a set of data
      regarding the current etiopathogenesis models of depression, with a particular
      attention to the neurobiological correlates and vulnerability factors. 

PMID- 25614754
TI  - Hemodynamic responses of unfit healthy women at a training session with nintendo
      wii: a possible impact on the general well-being.
AB  - AIMS: The purpose of this study was assess the effect of a training session with
      Nintendo Wii(r) on the hemodynamic responses of healthy women not involved in
      regular physical exercise. METHOD: Twenty-five healthy unfit women aged 28 +/- 6
      years played for 10 minutes the game Free Run (Wii Fit Plus). The resting heart
      rate (RHR), systolic and diastolic blood pressures (SBP and DBP), and double
      (rate-pressure) product (DP) were measured before and after activity. The HR
      during the activity (exercise heart rate, EHR) was measured every minute.
      RESULTS: A statistically significant difference was observed between the RHR (75
      +/- 9 bpm) and the mean EHR (176 +/- 15 bpm) (P < 0.001). The EHR remained in the
      target zone for aerobic exercise until the fifth minute of activity, which
      coincided with the upper limit of the aerobic zone (80% heart rate reserve (HRR)
      + RHR) from the sixth to tenth minute. The initial (110 +/- 8 mmHg) and final
      (145 +/- 17 mmHg) SBP (P < 0.01) were significantly different, as were the
      initial (71 +/- 8 mmHg) and final (79 +/- 9 mmHg) DBP (P < 0.01). A statistically
      significant difference was observed between the pre- (8.233 +/- 1.141 bpm-mmHg)
      and post-activity (25.590 +/- 4.117 bpm-mmHg) DP (P < 0.01). CONCLUSION: Physical
      exercise while playing Free Run sufficed to trigger acute hemodynamic changes in
      healthy women who were not engaged in regular physical exercise.

PMID- 25614752
TI  - Acupuncture for visceral pain: neural substrates and potential mechanisms.
AB  - Visceral pain is the most common form of pain caused by varied diseases and a
      major reason for patients to seek medical consultation. Despite much advances,
      the pathophysiological mechanism is still poorly understood comparing with its
      somatic counterpart and, as a result, the therapeutic efficacy is usually
      unsatisfactory. Acupuncture has long been used for the management of numerous
      disorders in particular pain and visceral pain, characterized by the high
      therapeutic benefits and low adverse effects. Previous findings suggest that
      acupuncture depresses pain via activation of a number of neurotransmitters or
      modulators including opioid peptides, serotonin, norepinephrine, and adenosine
      centrally and peripherally. It endows us, by advancing the understanding of the
      role of ion channels and gut microbiota in pain process, with novel perspectives
      to probe the mechanisms underlying acupuncture analgesia. In this review, after
      describing the visceral innervation and the relevant afferent pathways, in
      particular the ion channels in visceral nociception, we propose three principal
      mechanisms responsible for acupuncture induced benefits on visceral pain.
      Finally, potential topics are highlighted regarding the future studies in this
      field. 

PMID- 25614755
TI  - A Comparison between Children with ADHD and Children with Epilepsy in Self-Esteem
      and Parental Stress Level.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is frequently associated with
      negative psychological outcomes. This study explores the relationship between
      self-esteem, ADHD symptoms and parental stress. It compares children with ADHD,
      children with epilepsy (E) and typical developmental controls (TD). Participants
      included 65 children (aged 9-12 yrs) and their parents. The assessment was
      conducted by Multidimensional Self-Concept Scale (MSCS), Parent Stress Index
      (PSI) and Conners' Parent Rating Scales-Revised. Significant differences were
      found in Social, Competence and Academic areas of self-esteem between children
      with ADHD, with E and TD. Moreover, parents of children with ADHD showed a higher
      overall stress than both other groups. In conclusion, it seems important to
      evaluate the psychological aspects of ADHD con-dition, both in children and in
      parents, in order to suggest an individual multimodal treatment. 

PMID- 25614756
TI  - How many Assertive Community Treatment Teams are Needed in Japan? Estimate from
      Need Survey in Sendai City.
AB  - Despite the increasing ACT teams in Japan, no research exists on the need of ACT
      within the Japanese mental health system. The aim of this study was to describe
      the needs and feasibility of ACT teams. Furthermore, we estimated the number of
      po-tential ACT users and ACT teams needed in Japan. This study consists of two
      cross-sectional surveys in Sendai city. The primary survey was a self-completed
      questionnaire on the need and feasibility of ACT. In the secondary survey, the
      number of patients eligible for ACT was estimated based on primary physicians'
      evaluations. In the primary survey, 17 of the 57 in-stitutions responded
      (response rate 29.8%). All respondents answered that ACT teams are needed in the
      city of Sendai and "Crisis response" was as the most needed role of ACT. Based on
      the results of the secondary survey, approximately 900 to 3,600 patients in
      Sendai are estimated to be eligible for ACT. This finding indicates that the
      estimated number of ACT teams needed for 100,000 populations is from 0.9 to 3.5
      in Japan, a result that is in general agreement with data from other coun-tries. 

PMID- 25614757
TI  - WallProtDB, a database resource for plant cell wall proteomics.
AB  - BACKGROUND: During the last fifteen years, cell wall proteomics has become a
      major research field with the publication of more than 50 articles describing
      plant cell wall proteomes. The WallProtDB database has been designed as a tool to
      facilitate the inventory, the interpretation of cell wall proteomics data and the
      comparisons between cell wall proteomes. RESULTS: WallProtDB
      (http://www.polebio.lrsv.ups-tlse.fr/WallProtDB/) presently contains 2170
      proteins and ESTs identified experimentally in 36 cell wall proteomics studies
      performed on 11 different plant species. Two criteria have to be met for entering
      WallProtDB. First one is related to the identification of proteins. Only proteins
      identified in plant with available genomic or ESTs data are considered to ensure
      unambiguous identification. Second criterion is related to the difficulty to
      obtain clean cell wall fractions. Indeed, since cell walls constitute an open
      compartment difficult to isolate, numerous proteins predicted to be intracellular
      and/or having functions inside the cell have been identified in cell wall
      extracts. Then, except proteins predicted to be plasma membrane proteins, only
      proteins having a predicted signal peptide and no known intracellular retention
      signal are included in the database. In addition, WallProtDB contains information
      about the strategies used to obtain cell wall protein extracts and to identify
      proteins by mass spectrometry and bioinformatics. Mass spectrometry data are
      included when available. All the proteins of WallProtDB are linked to ProtAnnDB,
      another database, which contains structural and functional bioinformatics
      annotations of proteins as well as links to other databases (Aramemnon, CAZy,
      Planet, Phytozome). A list of references in the cell wall proteomics field is
      also provided. CONCLUSIONS: WallProtDB aims at becoming a cell wall proteome
      reference database. It can be updated at any time on request and provide a
      support for sharing cell wall proteomics data and literature references with
      researchers interested in plant cell wall biology.

PMID- 25614758
TI  - Robust dose-response curve estimation applied to high content screening data
      analysis.
AB  - BACKGROUND AND METHOD: Successfully automated sigmoidal curve fitting is highly
      challenging when applied to large data sets. In this paper, we describe a robust
      algorithm for fitting sigmoid dose-response curves by estimating four parameters
      (floor, window, shift, and slope), together with the detection of outliers. We
      propose two improvements over current methods for curve fitting. The first one is
      the detection of outliers which is performed during the initialization step with
      correspondent adjustments of the derivative and error estimation functions. The
      second aspect is the enhancement of the weighting quality of data points using
      mean calculation in Tukey's biweight function. RESULTS AND CONCLUSION: Automatic
      curve fitting of 19,236 dose-response experiments shows that our proposed method
      outperforms the current fitting methods provided by MATLAB(r);'s nlinfit function
      and GraphPad's Prism software.

PMID- 25614759
TI  - Absence of change in the gray matter volume of patients with ulcerative colitis
      in remission: a voxel based morphometry study.
AB  - BACKGROUND: Recent neuroimaging studies have investigated the brain involvement
      in patients with Crohn's disease (CD) and Ulcerative Colitis (UC). Functional
      studies found abnormalities in cognitive and emotional functions in CD and UC,
      while a voxel based morphometry (VBM) study found morphological changes in CD. We
      conducted a VBM study to compare the gray matter (GM) volume of UC patients and
      controls. METHODS: Eighteen UC patients in remission and eighteen healthy
      controls underwent structural MRI. VBM is a fully automated technique allowing
      identification of regional differences in the amount of GM, which enables an
      objective analysis of the whole brain. VBM was used for comparisons between
      patients and controls. RESULTS: UC patients were all in remission and had a mild
      clinical course. There were no differences between patients and controls in GM
      volume. CONCLUSION: The brain morphology of patients with UC in remission is
      similar to controls. The lack of GM abnormalities in UC patients might reflect
      the mild clinical course of the inflammatory bowel disorder. Further research
      involving patients with different degrees of disease severity or during flares
      could shed more light on potential brain structural changes in UC.

PMID- 25614760
TI  - Development of an ecological momentary assessment scale for appetite.
AB  - BACKGROUND: An understanding of eating behaviors is an important element of
      health education and treatment in clinical populations. To understand the
      biopsychosocial profile of eating behaviors in an ecologically valid way,
      ecological momentary assessment (EMA) is appropriate because its use is able to
      overcome the recall bias in patient-reported outcomes (PROs). As appetite is a
      key PRO associated with eating behaviors, this study was done to develop an EMA
      scale to evaluate the within-individual variation of momentary appetite and uses
      this scale to discuss the relationships between appetite and various
      psychological factors. METHODS: Twenty healthy participants (age 23.6 +/- 4.2
      years old) wore a watch-type computer for a week. Several times a day, including
      just before and after meals, they recorded their momentary psychological stress,
      mood states, and ten items related to appetite. In addition, they recorded
      everything they ate and drank into a personal digital assistant (PDA)-based food
      diary. Multilevel factor analysis was used to investigate the factor structure of
      the scale, and the reliability and validity of the scale were also explored.
      RESULTS: Multilevel factor analyses found two factors at the within-individual
      level (hunger/fullness and cravings) and one factor at the between-individual
      level. Medians for the individually calculated Cronbach's alphas were 0.89 for
      hunger/fullness, 0.71 for cravings, and 0.86 for total appetite (the sum of all
      items). Hunger/fullness, cravings, and total appetite all decreased significantly
      after meals compared with those before meals, and hunger/fullness, cravings, and
      total appetite before meals were positively associated with energy intake. There
      were significant negative associations between both hunger/fullness and total
      appetite and anxiety and depression as well as between cravings, and depression,
      anxiety and stress. CONCLUSIONS: The within-individual reliability of the EMA
      scale to assess momentary appetite was confirmed in most subjects and it was also
      validated as a useful tool to understand eating behaviors in daily settings.
      Further refinement of the scale is necessary and further investigations need to
      be conducted, particularly on clinical populations.

PMID- 25614761
TI  - Nanomechanics of phospholipid LB film studied layer by layer with AFM.
AB  - BACKGROUND: Phospholipid, a main component of cell membrane, has been explored as
      a model system of the cell membrane and temporary scaffold materials in recent
      studies. The mechanical properties of phospholipid layers are essentially
      interesting since it is involved in several biological processes. RESULTS: Here,
      the nanomechanical properties such as indentation force, adhesion force and DMT
      (Derjaguin-Muller-Toporov) modulus of 1,2-distearoyl-sn-glycero-3-phosphocholine
      (DSPC) Langmuir-Blodgett (LB) films were analyzed layer by layer with Atomic
      Force Microscope (AFM) under deionized water condition. CONCLUSIONS: The
      penetration distances in the indentation force curves are equal to the
      thicknesses of phospholipid films, and the yield forces of DSPC LB films in
      deionized water are smaller than that of similar lipid films in buffered
      solutions due to the influence of ions. Moreover, the DMT modulus of upper layer
      DSPC LB film is different from that of monolayer DSPC LB film due to the
      influence of their different substrates. Our results suggest that environment
      such as surrounding ions and substrate will strongly influence the measured nano
      mechanical properties of the lipid bilayer, especially that of the down layer.
      Graphical AbstractA process about the exploration of nanomechanics of DSPC LB
      film.

PMID- 25614762
TI  - A randomized effectiveness trial of individual child social skills training: six
      month follow-up.
AB  - BACKGROUND: Individual Social Skills Training (ISST) is a short term,
      individually delivered intervention (8-10 sessions) that promotes social skills
      in children with emerging or existing conduct problems. This study examined the
      effectiveness of ISST immediately and 6 months after the termination of the
      intervention. METHODS: The participants were 198 children (3-12 years) who were
      randomly assigned to ISST or practice as usual. The data were collected from
      parents, children and teachers. RESULTS: Findings showed positive change on most
      outcomes in both study conditions. However, examining the relative effectiveness
      of the intervention, only one positive effect of ISST emerged on parent-reported
      child conduct problems immediately after intervention. CONCLUSIONS: These results
      suggest that compared to the control group, ISST had limited effects in
      ameliorating child problem behavior. These data suggest that it is not sufficient
      to provide ISST when aiming to reduce conduct problems in children.

PMID- 25614763
TI  - Karyotypic evolutions of cancer species in rats during the long latent periods
      after injection of nitrosourea.
AB  - BACKGROUND: A century of research has established that cancers arise from tissues
      exposed to carcinogens only after long latencies of years to decades and have
      individual clonal karyotypes. Since speciation from known precursors also depends
      on long latencies and new species also have individual karyotypes, we and others
      have recently proposed that carcinogenesis is a form of speciation. According to
      this theory karyotypic evolutions generate new cancer species from normal cells
      as follows: Carcinogens induce aneuploidy (Figure 1). By unbalancing thousands of
      genes aneuploidy automatically destabilizes the karyotype and thus catalyzes
      random karyotypic variations. Selections of variants with proliferative
      phenotypes form non-clonal hyperplasias with persistently varying karyotypes.
      Very rare karyotypic variations form new cancer species with individual clonal
      karyotypes. Despite destabilization by the resulting congenital aneuploidies,
      cancer karyotypes are stabilized within narrow margins of variation by clonal
      selections for cancer-specific autonomy. Because all non-cancerous aneuploidies
      are unstable, all aneusomies of prospective cancers are joined in single-steps,
      rather than gradually. Since this mechanism is very inefficient, it predicts long
      latent periods from carcinogens to cancers and individual clonal cancer
      karyotypes. RESULTS: Here we have tested the predicted roles of karyotypic
      evolutions during the time course of carcinogenesis in an established
      experimental system. In this system injection of nitrosourea induces in female
      rats non-invasive mammary hyperplasias ("tumors") after two or more months, and
      invasive carcinomas after six or more months. Accordingly four specific
      predictions were tested: (1) Invasive cancers are late and carry individual
      clonal karyotypes and phenotypes, (2) Persistent hyperplasias carry non-clonal
      karyotypes, (3) Non-clonal hyperplasias generate clonal cancers spontaneously but
      rarely, (4) Cancer-karyotypes arise with all individual clonal aneusomies in
      single-steps. All four predictions were experimentally confirmed. CONCLUSIONS:
      Our results along with the literature reveal a coherent karyotypic mechanism of
      carcinogenesis: Carcinogens induce aneuploidy. The inherent instability of
      aneuploidy automatically catalyzes new karyotypic variations. Aneuploid
      karyotypes with proliferative phenotypes form varying non-clonal hyperplasias.
      Rare variations form cancer species with individual clonal karyotypes, which are
      stabilized by clonal selection for autonomy. The low odds of this mechanism
      explain the long latencies of carcinogenesis, the individuality and karyotypic
      clonality of cancers.

PMID- 25614764
TI  - Synthetic learning machines.
AB  - BACKGROUND: Using a collection of different terminal nodesize constructed random
      forests, each generating a synthetic feature, a synthetic random forest is
      defined as a kind of hyperforest, calculated using the new input synthetic
      features, along with the original features. RESULTS: Using a large collection of
      regression and multiclass datasets we show that synthetic random forests
      outperforms both conventional random forests and the optimized forest from the
      regresssion portfolio. CONCLUSIONS: Synthetic forests removes the need for tuning
      random forests with no additional effort on the part of the researcher.
      Importantly, the synthetic forest does this with evidently no loss in prediction
      compared to a well-optimized single random forest.

PMID- 25614765
TI  - Global gene expression profiling identifies new therapeutic targets in acute
      Kawasaki disease.
AB  - BACKGROUND: Global gene expression profiling can provide insight into the
      underlying pathophysiology of disease processes. Kawasaki disease (KD) is an
      acute, self-limited vasculitis whose etiology remains unknown. Although the
      clinical illness shares certain features with other pediatric infectious
      diseases, the occurrence of coronary artery aneurysms in 25% of untreated
      patients is unique to KD. METHODS: To gain further insight into the molecular
      mechanisms underlying KD, we investigated the acute and convalescent whole blood
      transcriptional profiles of 146 KD subjects and compared them with the
      transcriptional profiles of pediatric patients with confirmed bacterial or viral
      infection, and with healthy control children. We also investigated the transcript
      abundance in patients with different intravenous immunoglobulin treatment
      responses and different coronary artery outcomes. RESULTS: The overwhelming
      signature for acute KD involved signaling pathways of the innate immune system.
      Comparison with other acute pediatric infections highlighted the importance of
      pathways involved in cell motility including paxillin, relaxin, actin, integrins,
      and matrix metalloproteinases. Most importantly, the IL1beta pathway was
      identified as a potential therapeutic target. CONCLUSION: Our study revealed the
      importance of the IL-1 signaling pathway and a prominent signature of innate
      immunity and cell migration in the acute phase of the illness.

PMID- 25614766
TI  - How behavioral economics can help to avoid 'The last mile problem' in whole
      genome sequencing.
AB  - Failure to consider lessons from behavioral economics in the case of whole genome
      sequencing may cause us to run into the 'last mile problem' - the failure to
      integrate newly developed technology, on which billions of dollars have been
      invested, into society in a way that improves human behavior and decision-making.

PMID- 25614767
TI  - Are inflammatory profiles the key to personalized Alzheimer's treatment?
AB  - There is currently no disease-modifying treatment for Alzheimer's disease (AD)
      and the need is great as the number of people diagnosed with AD is predicted to
      steadily increase. Inflammation is associated with AD, and is predictive of more
      advanced disease pathology and cognitive impairment. Moreover, preventing
      inflammation reduces the risk of developing AD. However, clinical trials with
      anti-inflammatory treatment have not been successful. One reason may be that
      there is diversity in the immune response and reducing immune activity with anti
      inflammatories is not appropriate in all conditions. Recently, we have begun to
      apply categorizations, used to characterize the peripheral immune response, to
      the immune processes of the brain. When we do this, we are able to describe an
      individual's inflammatory profile within this spectrum. We have observed that
      patients with early AD are distributed across two broad categories of immune
      activation. If we recognize the diversity within this cohort of individuals with
      early AD and use information about immune phenotypes to guide the choice of
      treatment, then we may expect better clinical outcomes.

PMID- 25614768
TI  - Temperature Profiles Along the Root with Gutta-percha Warmed through Different
      Heat Sources.
AB  - OBJECTIVES: To evaluate temperature profiles developing in the root during warm
      compaction of gutta-percha with the heat sources System B and System MB Obtura
      (Analityc Technology, Redmond, WA, USA). Thirty extracted human incisor teeth
      were used. Root canals were cleaned and shaped by means of Protaper rotary files
      (Dentsply-Maillefer, Belgium), and imaging was performed by micro-CT (Skyscan
      1072, Aartselaar, Belgium). METHODS: Teeth were instrumented with K-type
      thermocouples, and the roots were filled with thermoplastic gutta-percha.
      Vertical compaction was achieved through the heat sources System B and System MB,
      and temperature profiles were detect-ed by means of NI Dac Interface controlled
      by the LabView System. With both heat sources, higher temperature levels were
      recorded in the region of the root far from the apex. When the warm plugger tip
      was positioned at a distance of 3 mm from the root apex, temperature levels of
      about 180 degrees C were used to soften gutta-percha, and no statistically
      significant differences were observed between peak temperatures developed by the
      two heating sources at the root apex. However, a temperature level higher than 40
      degrees C was maintained for a longer time with System MB. RESULTS: Statistically
      significant differences were observed in peak temperature levels recorded far
      from the root apex. Thus, with a temperature of about 180 degrees C and the warm
      plugger positioned at 3 mm from the root apex, both heating sources led to a
      temperature slightly higher than 40 degrees C at the apex of the root, suggesting
      that the gutta-percha was properly softened. SIGNIFICANCE: A temperature level
      higher than 40 degrees C was maintained for a longer time with System MB, thus
      providing an ad-equate time for warm compaction of the gutta-percha.

PMID- 25614769
TI  - The True-Positive Rate of a Screening Questionnaire for Temporomandib-ular
      Disorders.
AB  - BACKGROUND: Temporomandibular disorders (TMD) occur at an incidence of 5-12% in
      the general population. We aimed to investigate the rate of true-positives for a
      screening questionnaire for TMD (SQ-TMD) and differences in the characteristics
      between the true-positive and false-negative groups. Materials and. METHODS:
      Seventy-six individuals (16 men, 60 women; mean age, 41.1 +/- 16.5 years) were
      selected from pa-tients with TMD who had visited the Temporomandibular Joint
      Clinic at Tokyo Medical and Dental University. The patients were assessed using a
      questionnaire that contained items on TMD screening (SQ-TMD); pain intensity (at
      rest, maximum mouth-opening, and chewing), as assessed using the visual analog
      scale (VAS); and TMD-related limitations of daily func-tion (LDF-TMD). A logistic
      regression analysis was performed to assess the factors potentially influencing
      the true-positive rate. RESULTS: Of the 76 subjects, 62 (81.6%) were true
      positive for the questionnaire based on the SQ-TMD scores. The mean VAS score for
      maximum mouth-opening and chewing and the mean LDF-TMD score were significantly
      greater in the true-positive group than those in the false-negative group. The
      results of the logistic regression analysis showed that only the VAS score for
      chewing was a statistically significant factor (P < 0.05). CONCLUSION: The true
      positive rate of TMD using SQ-TMD was very high. The results indicate that SQ-TMD
      can be used to screen TMD in patients with moderate or severe pain and difficulty
      in living a healthy daily life.

PMID- 25614770
TI  - A comparison of shear bond strength of ceramic and resin denture teeth on
      different acrylic resin bases.
AB  - The purpose of this study is to compare the shear bond strength of different
      resin bases and artificial teeth made of ceramic or acrylic resin materials and
      whether tooth-base interface may be treated with aluminium oxide sandblasting.
      Experimental measurements were carried on 80 specimens consisting of a cylinder
      of acrylic resin into which a single tooth is inserted. An ad hoc metallic frame
      was realized to measure the shear bond strength at the tooth-base interface. A
      complete factorial plan was designed and a three-way ANalysis Of VAriance (ANOVA)
      was carried out to investigate if shear bond strength is affected by the
      following factors: (i) tooth material (ceramic or resin); (ii) base material
      (self-curing or thermal-curing resin); (iii) presence or absence of aluminium
      oxide sandblasting treatment at the tooth-base interface. Tukey post hoc test was
      also conducted to evaluate any statistically significant difference between shear
      strength values measured for the dif-ferently prepared samples. It was found from
      ANOVA that the above mentioned factors all affect shear strength. Furthermore,
      post hoc analysis indi-cated that there are statistically significant differences
      (p-value=0.000) between measured shear strength values for: (i) teeth made of
      ceramic material vs. teeth made of acrylic resin material; (ii) bases made of
      self-curing resin vs. thermal-curing resin; (iii) specimens treated with
      aluminium oxide sandblasting vs. untreated specimens. Shear strength values
      measured for acryl-ic resin teeth were on average 70% higher than those measured
      for ceramic teeth. The shear bond strength was maximized by preparing samples
      with thermal-curing resin bases and resin teeth submitted to aluminium oxide
      sandblasting. 

PMID- 25614771
TI  - Repeatability of the evaluation of perception of dyspnea in normal subjects
      assessed through inspiratory resistive loads.
AB  - PURPOSE: Study the repeatability of the evaluation of the perception of dyspnea
      using an inspiratory resistive loading system in healthy subjects. METHODS: We
      designed a cross sectional study conducted in individuals aged 18 years and
      older. Perception of dyspnea was assessed using an inspiratory resistive load
      system. Dyspnea was assessed during ventilation at rest and at increasing
      resistive loads (0.6, 6.7, 15, 25, 46.7, 67, 78 and returning to 0.6 cm H2O/L/s).
      After breathing in at each level of resistive load for two minutes, the subject
      rated the dyspnea using the Borg scale. Subjects were tested twice (intervals
      from 2 to 7 days). RESULTS: Testing included 16 Caucasian individuals (8 male and
      8 female, mean age: 36 years). The median scores for dyspnea rating in the first
      test were 0 at resting ventilation and 0, 2, 3, 4, 5, 7, 7 and 1 point,
      respectively, with increasing loads. The median scores in the second test were 0
      at resting and 0, 0, 2, 2, 3, 4, 4 and 0.5 points, respectively. The intra-class
      correlation coefficient was 0.57, 0.80, 0.74, 0.80, 0.83, 0.86, 0.91, and 0.92
      for each resistive load, respectively. In a generalized linear model analysis,
      there was a statistically significant difference between the levels of resistive
      loads (p<0.001) and between tests (p=0.003). Dyspnea scores were significantly
      lower in the second test. CONCLUSION: The agreement between the two tests of the
      perception of dyspnea was only moderate and dyspnea scores were lower in the
      second test. These findings suggest a learning effect or an effect that could be
      at least partly attributed to desensitization of dyspnea sensation in the brain.

PMID- 25614772
TI  - Angiosarcoma presenting with spontaneous hydropneumothorax: report of a case and
      review of the literature.
AB  - Angiosarcoma is a rare malignant tumor of soft tissue. Because angiosarcoma
      originates from endothelial cells, it can occur in any organ and shows aggressive
      clinical features. Most commonly, angiosarcoma initially presents as a cutaneous
      lesion. Lung metastasis from scalp angiosarcoma can develop pneumothorax. We
      report a case of multiorgan involvement of an angiosarcoma, including the scalp,
      initially presenting with hydropneumothorax. Immunohistochemistry analysis of the
      cells obtained from the study confirmed the pleural invasion of the angiosarcoma.

PMID- 25614773
TI  - Felty's Syndrome, Insights and Updates.
AB  - Felty's syndrome (FS) is characterized by the triad of seropositive rheumatoid
      arthritis (RA) with destructive joint involvement, splenomegaly and neutropenia.
      Current data shows that 1-3 % of RA patients are complicated with FS with an
      estimated prevalence of 10 per 100,000 populations. The complete triad is not an
      absolute requirement, but persistent neutropenia with an absolute neutrophil
      count (ANC) generally less than 1500/mm3 is necessary for establishing the
      diagnosis. Felty's syndrome may be asymptomatic but serious local or systemic
      infections may be the first clue to the diagnosis. FS is easily overlooked by
      parallel diagnoses of Sjogren syndrome or systemic lupus erythematosus or
      lymphohematopoietic malignancies. The role of genetic (HLA DR4) is more prominent
      in FS in comparison to classic rheumatoid arthritis. There is large body of
      evidence that in FS patients, both cellular and humoral immune systems
      participate in neutrophil activation, and apoptosis and its adherence to
      endothelial cells in the spleen. It has been demonstrated that proinflammatory
      cytokines may have inhibitory effects on bone marrow granulopoiesis. Binding of
      IgGs to neutrophil extracellular chromatin traps (NET) leading to neutrophil
      death plays a crucial role in its pathophysiology. In turn, "Netting" neutrophils
      may activate auto-reactive B cells leading to further antibody and immune complex
      formation. In this review we discuss on basic pathophysiology, epidemiology,
      genetics, clinical, laboratory and treatment updates of Felty's syndrome. 

PMID- 25614774
TI  - Individuals with primary osteoarthritis have different phenotypes depending on
      the affected joint - a case control study from southern sweden including 514
      participants.
AB  - OBJECTIVE: The aim of this study was to evaluate whether primary osteoarthritis
      (OA), independent of affected joint, is associated with a phenotype that is
      different from the phenotype in a normative cohort. Material and. METHODS: We
      included 274 patients with primary OA, 30 women and 32 men (mean age 66 years,
      range 42-84) with primary hip OA, 38 women and 74 men (mean age 61 years; range
      34-85) with primary knee OA, 42 women and 19 men (men age 64 years, range 42-87)
      with primary ankle or foot OA and 20 women and 19 men (mean age 66 years, range
      47-88) with primary hand or finger OA. Of all patients included with OA, 23% had
      hip OA, 41% knee OA, 22% ankle or foot OA and 14% hand or finger OA. Serving as
      references were 122 women and 118 men of the same ages who were population-based,
      included as a control cohort. We measured total body BMD (g/cm2) and proportion
      of fat and lean mass (%) with dual energy X-ray absorptiometry. Height, weight
      and BMI (kg/m2) were also assessed. We then calculated Z-scores (number of
      standard deviations difference from the mean value of the control cohort) in the
      OA patients and compared these between the groups. RESULTS: Individuals with hand
      OA and controls had similar phenotype. Individuals with lower extremity OA,
      irrespective of the affected joint, had similar weight, BMI and BMD, but higher
      than in individuals with hand OA and controls (all p<0.05). Individuals with
      lower extremity OA had higher fat and lower lean mass than individuals with hand
      OA and controls (all p<0.001). CONCLUSION: Individuals with primary OA in the
      lower extremity have a phenotype with higher BMD, higher BMI, proportionally
      higher fat content and lower lean body mass content. The different skeletal
      phenotypes in our patients with OA in the lower extremity and patients with hand
      OA indicate that separate pathophysiologic pathways may be responsible for
      primary OA in different joints.

PMID- 25614775
TI  - LETTER TO THE EDITOR Revision of Unicondylar to Total Knee Arthoplasty: A
      Systematic Review.

PMID- 25614777
TI  - SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte
      protection in angiotensin II-induced heart hypertrophy.
AB  - BACKGROUND: Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could
      activate cell survival machinery and has been shown to be protective in
      regulation of heart function. Here, we determined the mechanism by which SIRT1
      regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo
      and in vitro. METHODS: We analyzed SIRT1 expression in the hearts of control and
      AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and
      pretreated with 17beta-estradiol to measure SIRT1 expression. Protein synthesis,
      cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot
      were performed on AngII-induced mouse heart hypertrophy samples and cultured
      neonatal rat ventricular myocytes (NRVMs) to investigate the function of SIRT1.
      RESULTS: SIRT1 expression was slightly upregulated in AngII-induced mouse heart
      hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte
      apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy
      and apoptosis. 17beta-Estradiol was able to protect cardiomyocytes from AngII
      induced injury with a profound upregulation of SIRT1 and activation of AMPK.
      Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide
      could block SIRT1's protective effect. CONCLUSIONS: These results indicate that
      SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte
      protection during AngII-induced heart hypertrophy and injury.

PMID- 25614776
TI  - Oxidative stress associated with neuronal apoptosis in experimental models of
      epilepsy.
AB  - Epilepsy is considered one of the most common neurological disorders worldwide.
      Oxidative stress produced by free radicals may play a role in the initiation and
      progression of epilepsy; the changes in the mitochondrial and the oxidative
      stress state can lead mechanism associated with neuronal death pathway.
      Bioenergetics state failure and impaired mitochondrial function include excessive
      free radical production with impaired synthesis of antioxidants. This review
      summarizes evidence that suggest what is the role of oxidative stress on
      induction of apoptosis in experimental models of epilepsy. 

PMID- 25614778
TI  - The combined extract of purple waxy corn and ginger prevents cataractogenesis and
      retinopathy in streptozotocin-diabetic rats.
AB  - Based on the crucial roles of oxidative stress and aldose reductase on diabetic
      complications and the protective effect against diabetic eye complication of
      purple waxy corn and ginger (PWCG) together with the synergistic effect concept,
      we aimed to determine anticataract and antiretinopathy effects of the combined
      extract of purple waxy corn and ginger (PWCG). The streptozotocin diabetics with
      the blood glucose levels >250 mg.dL(-1) were orally given the extract at doses of
      50, 100, and 200 mg/kg.BW(-1) for 10 weeks. Then, lens opacity and histopathology
      of retina were determined. The changes of MDA together with the activities of
      SOD, CAT, GPx, and AR in lens were also determined using biochemical assays. All
      doses of PWCG decreased lens opacity, MDA, and AR in the lens of diabetic rats.
      The elevation of CAT and GPx activities was also observed. The antiretinopathy
      property of the combined extract was also confirmed by the increased number of
      neurons in ganglion cell layer and thickness of total retina and retinal nuclear
      layer in diabetic rats. PWCG is the potential functional food to protect against
      diabetic cataract and retinopathy. However, further studies concerning toxicity
      and clinical trial are still essential.

PMID- 25614779
TI  - Personality Change Pre- to Post- Loss in Spousal Caregivers of Patients with
      Terminal Lung Cancer.
AB  - Personality is relatively stable in adulthood but could change in response to
      life transitions, such as caring for a spouse with a terminal illness. Using a
      case-control design, spousal caregivers (n=31) of patients with terminal lung
      cancer completed the NEO-FFI twice, 1.5 years apart, before and after the
      patient's death. A demographically-matched sample of community controls (n=93)
      completed the NEO-FFI on a similar timeframe. Based on research and theory, we
      hypothesized that bereaved caregivers would experience greater changes than
      controls in interpersonal facets of extraversion (sociability), agreeableness
      (prosocial, nonantagonistic), and conscientiousness (dependability). Consistent
      with hypotheses, bereaved caregivers experienced an increase in interpersonal
      orientation, becoming more sociable, prosocial, and dependable (Cohen's d = .48
      .67), though there were no changes in nonantagonism. Changes were not observed in
      controls (ds <= .11). These initial findings underscore the need for more
      research on the effect of life transitions on personality.

PMID- 25614780
TI  - Neurodegeneration with brain iron accumulation: diagnosis and management.
AB  - Neurodegeneration with brain iron accumulation (NBIA) encompasses a group of
      inherited disorders that share the clinical features of an extrapyramidal
      movement disorder accompanied by varying degrees of intellectual disability and
      abnormal iron deposition in the basal ganglia. The genetic basis of ten forms of
      NBIA is now known. The clinical features of NBIA range from rapid global
      neurodevelopmental regression in infancy to mild parkinsonism with minimal
      cognitive impairment in adulthood, with wide variation seen between and within
      the specific NBIA sub-type. This review describes the clinical presentations,
      imaging findings, pathologic features, and treatment considerations for this
      heterogeneous group of disorders. 

PMID- 25614781
TI  - Current Status of Huntington's Disease in Korea: A Nationwide Survey and National
      Registry Analysis.
AB  - OBJECTIVE: Huntington's disease (HD) is a rare neurological disorder, and its
      current status in Korea is not well investigated. This study aims to determine
      the prevalence and incidence of HD and to investigate the clinical features of HD
      patients in Korea. METHODS: We estimated the crude prevalence and annual
      incidence of HD based on the databases of the Rare Diseases Registry (RDR) and
      the National Health Insurance (NHI). The clinical data of genetically confirmed
      HD patients was collected from 10 referral hospitals and analyzed. RESULTS: The
      mean calculated annual incidence was 0.06 cases per 100,000 persons, and the mean
      calculated prevalence was 0.38 based on the NHI database. The estimated crude
      prevalence based on the RDR was 0.41. Of the sixty-eight HD patients recruited,
      the mean age of onset was 44.16 +/- 14.08 years and chorea was most frequently
      reported as the initial symptom and chief complaint. The mean CAG repeat number
      of the expanded allele was 44.7 +/- 4.8 and correlated inversely with the age of
      onset (p < 0.001). About two-thirds of the patients have a positive family
      history, and HD patients without positive family history showed a delay in onset
      of initial symptoms, a prolonged interval between initial symptom onset and
      genetic diagnosis and a delay in the age of genetic diagnosis. CONCLUSIONS: To
      the best of our knowledge, this is the first study to estimate the prevalence and
      incidence of HD in Korea and the largest HD series in the Asian population. Our
      analyses might be useful for further studies and large-scale investigations in HD
      patients.

PMID- 25614782
TI  - Apathy and olfactory dysfunction in early Parkinson's disease.
AB  - OBJECTIVE: Olfactory and emotional dysfunctions are very common in patients with
      Parkinson's disease (PD). Olfaction and emotions share common neuroanatomical
      substrates. Therefore, in this study, we evaluated the association between
      olfactory and emotional dysfunctions in patients with PD. METHODS: Parkinson's
      disease patients who had been assessed for their olfactory function and
      neuropsychiatric symptoms including emotional dysfunction were included. A
      logistic regression analysis was performed to evaluate the association between
      low olfaction and different neuropsychiatric symptoms. RESULTS: The patients with
      low olfaction (cross cultural smell identification test score <= 6) showed a
      higher prevalence of apathy when compared with those with high olfaction, whereas
      the frequencies of other neuropsychiatric symptoms were comparable between the
      two groups. A multivariate logistic regression analysis revealed that the
      presence of apathy/indifference [odds ratio (OR) = 2.859, p = 0.007], age 70
      years or more (OR = 2.281, p = 0.009), and the male gender (OR = 1.916, p =
      0.030) were significantly associated with low olfaction. CONCLUSIONS: Our results
      demonstrate that apathy/indifference is a unique emotional dysfunction associated
      with olfactory dysfunction in PD. The findings also suggest that PD patients with
      low olfaction have a high prevalence of apathy.

PMID- 25614783
TI  - Neuropsychiatric symptoms in Parkinson's disease dementia are associated with
      increased caregiver burden.
AB  - OBJECTIVE: Neuropsychiatric symptoms are common in Parkinson's disease dementia
      (PDD). Frequent and severe neuropsychiatric symptoms create high levels of
      distress for patients and caregivers, decreasing their quality of life. The aim
      of this study was to investigate neuropsychiatric symptoms that may contribute to
      increased caregiver burden in PDD patients. METHODS: Forty-eight PDD patients
      were assessed using the 12-item Neuropsychiatric Inventory (NPI) to determine the
      frequency and severity of mental and behavioral problems. The Burden Interview
      and Caregiver Burden Inventory were used to evaluate caregiver burden. RESULTS:
      All but one patient showed one or more neuropsychiatric symptoms. The three most
      frequent neuropsychiatric symptoms were apathy (70.8%) and anxiety (70.8%),
      followed by depression (68.7%). More severe neuropsychiatric symptoms were
      significantly correlated with increased caregiver burden. The domains of
      delusion, hallucination, agitation and aggression, anxiety, irritability and
      lability, and aberrant motor behavior were associated with caregiver stress.
      After controlling for age and other potential confounding variables, total NPI
      score was significantly associated with caregiver burden. CONCLUSIONS: The
      results of this study confirm that neuropsychiatric symptoms are frequent and
      severe in patients with PDD and are associated with increased caregiver distress.
      A detailed evaluation and management of neuropsychiatric symptoms in PDD patients
      appears necessary to improve patient quality of life and reduce caregiver burden.

PMID- 25614784
TI  - Ataxia with vitamin e deficiency in norway.
AB  - OBJECTIVE: Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive
      neurological disorder which usually starts in childhood. The clinical
      presentation is very similar to Friedreich ataxia, most patients have progressive
      truncal and extremity ataxia, areflexia, positive Babinski sign, dysarthria and
      sensory neuropathy. METHODS: We made an inquiry to our colleagues in Norway, we
      included information from a prevalence study published southern Norway and added
      data from our own known case. RESULTS: A newly published prevalence study of
      hereditary ataxias (total of 171 subjects) found only one subject with AVED in
      Southeast Norway. We describe two more patients, one from the Central part and
      one from the Northern part of Norway. All 3 cases had age of onset in early
      childhood (age of 4-5 years) and all experienced gait ataxia and dysarthria. The
      genetic testing confirmed that they had pathogenic mutations in the alpha
      tocopherol transfer protein gene (TTPA). All were carriers of the non-sense
      c.400C > T mutation, one was homozygous for that mutation and the others were
      compound heterozygous, either with c.358G > A or c.513_514insTT. The homozygous
      carrier was by far the most severely affected case. CONCLUSIONS: We estimate the
      occurrence of AVED in Norway to be at least 0.6 per million inhabitants. We
      emphasize that all patients who develop ataxia in childhood should be routinely
      tested for AVED to make an early diagnosis for initiating treatment with high
      dose vitamin E to avoid severe neurological deficits.

PMID- 25614785
TI  - A patient with unilateral periodic leg movements associated with pontine
      infarction.

PMID- 25614786
TI  - Access to Formally Ni(I) States in a Heterobimetallic NiZn System.
AB  - Heterobimetallic NiZn complexes featuring metal centers in distinct coordination
      environments have been synthesized using diimine-dioxime ligands as binucleating
      scaffolds. A tetramethylfuran-containing ligand derivative enables a stable one
      electron-reduced S = 1/2 species to be accessed using Cp2Co as a chemical
      reductant. The resulting pseudo-square planar complex exhibits spectroscopic and
      crystallographic characteristics of a ligand-centered radical bound to a Ni(II)
      center. Upon coordination of a pi-acidic ligand such as PPh3, however, a five
      coordinate Ni(I) metalloradical is formed. The electronic structures of these
      reduced species provide insight into the subtle effects of ligand structure on
      the potential and reversibility of the NiII/I couple for complexes of redox
      active tetraazamacrocycles.

PMID- 25614787
TI  - Landscape variability explains spatial pattern of population structure of
      northern pike (Esox lucius) in a large fluvial system.
AB  - A growing number of studies have been investigating the influence of contemporary
      environmental factors on population genetic structure, but few have addressed the
      issue of spatial patterns in the variable intensity of factors influencing the
      extent of population structure, and particularly so in aquatic ecosystems. In
      this study, we document the landscape genetics of northern pike (Esox lucius),
      based on the analysis of nearly 3000 individuals from 40 sampling sites using 22
      microsatellites along the Lake Ontario - St. Lawrence River system (750 km) that
      locally presents diverse degrees of interannual water level variation. Genetic
      structure was globally very weak (F ST = 0.0208) but spatially variable with mean
      level of differentiation in the upstream section of the studied area being
      threefold higher (F ST = 0.0297) than observed in the downstream sector (F ST =
      0.0100). Beside interannual water level fluctuation, 19 additional variables were
      considered and a multiple regression on distance matrices model (R (2)  = 0.6397,
      P < 0.001) revealed that water masses (b = 0.3617, P < 0.001) and man-made dams
      (b = 0.4852, P < 0.005) reduced genetic connectivity. Local level of interannual
      water level stability was positively associated to the extent of genetic
      differentiation (b = 0.3499, P < 0.05). As water level variation impacts on
      yearly quality and localization of spawning habitats, our study illustrates how
      temporal variation in local habitat availability, caused by interannual water
      level fluctuations, may locally decrease population genetic structure by forcing
      fish to move over longer distances to find suitable habitat. This study thus
      represents one of the rare examples of how environmental fluctuations may
      influence spatial variation in the extent of population genetic structure within
      a given species. 

PMID- 25614788
TI  - Species-specific differences in relative eye size are related to patterns of edge
      avoidance in an Amazonian rainforest bird community.
AB  - Eye size shows a large degree of variation among species, even after correcting
      for body size. In birds, relatively larger eyes have been linked to predation
      risk, capture of mobile prey, and nocturnal habits. Relatively larger eyes
      enhance visual acuity and also allow birds to forage and communicate in low-light
      situations. Complex habitats such as tropical rain forests provide a mosaic of
      diverse lighting conditions, including differences among forest strata and at
      different distances from the forest edge. We examined in an Amazonian forest bird
      community whether microhabitat occupancy (defined by edge avoidance and forest
      stratum) was a predictor of relative eye size. We found that relative eye size
      increased with edge avoidance, but did not differ according to forest stratum.
      Nevertheless, the relationship between edge avoidance and relative eye size
      showed a nonsignificant positive trend for species that inhabit lower forest
      strata. Our analysis shows that birds that avoid forest edges have larger eyes
      than those living in lighter parts. We expect that this adaptation may allow
      birds to increase their active daily period in dim areas of the forest. The
      pattern that we found raises the question of what factors may limit the evolution
      of large eyes. 

PMID- 25614789
TI  - Estimating the spatial distribution of wintering little brown bat populations in
      the eastern United States.
AB  - Depicting the spatial distribution of wildlife species is an important first step
      in developing management and conservation programs for particular species.
      Accurate representation of a species distribution is important for predicting the
      effects of climate change, land-use change, management activities, disease, and
      other landscape-level processes on wildlife populations. We developed models to
      estimate the spatial distribution of little brown bat (Myotis lucifugus)
      wintering populations in the United States east of the 100th meridian, based on
      known hibernacula locations. From this data, we developed several scenarios of
      wintering population counts per county that incorporated uncertainty in the
      spatial distribution of the hibernacula as well as uncertainty in the size of the
      current little brown bat population. We assessed the variability in our results
      resulting from effects of uncertainty. Despite considerable uncertainty in the
      known locations of overwintering little brown bats in the eastern United States,
      we believe that models accurately depicting the effects of the uncertainty are
      useful for making management decisions as these models are a coherent
      organization of the best available information. 

PMID- 25614790
TI  - Trade-offs in seedling growth and survival within and across tropical forest
      microhabitats.
AB  - For niche differences to maintain coexistence of sympatric species, each species
      must grow and/or survive better than each of the others in at least one set of
      conditions (i.e., performance trade-offs). However, the extent of niche
      differentiation in tropical forests remains highly debated. We present the first
      test of performance trade-offs for wild seedlings in a tropical forest. We
      measured seedling relative growth rate (RGR) and survival of four common native
      woody species across 18 light, substrate, and topography microhabitats over 2.5
      years within Hawaiian montane wet forest, an ideal location due to its low
      species diversity and strong species habitat associations. All six species pairs
      exhibited significant performance trade-offs across microhabitats and for RGR
      versus survival within microhabitats. We also found some evidence of performance
      equivalence, with species pairs having similar performance in 26% of comparisons
      across microhabitats. Across species, survival under low light was generally
      positively associated with RGR under high light. When averaged over all species,
      topography (slope, aspect, and elevation) explained most of the variation in RGR
      attributable to microhabitat variables (51-53%) followed by substrate type (35
      37%) and light (11-12%). However, the relative effects of microhabitat differed
      among species and RGR metric (i.e., RGR for height, biomass, or leaf area). These
      findings indicate that performance trade-offs among species during regeneration
      are common in low-diversity tropical forest, although other mechanisms may better
      explain the coexistence of species with small performance differences. 

PMID- 25614791
TI  - In situ tagging technique for fishes provides insight into growth and movement of
      invasive lionfish.
AB  - Information on fish movement and growth is primarily obtained through the marking
      and tracking of individuals with external tags, which are usually affixed to
      anesthetized individuals at the surface. However, the quantity and quality of
      data obtained by this method is often limited by small sample sizes owing to the
      time associated with the tagging process, high rates of tagging-related
      mortality, and displacement of tagged individuals from the initial capture
      location. To address these issues, we describe a technique for applying external
      streamer and dart tags in situ, which uses SCUBA divers to capture and tag
      individual fish on the sea floor without the use of anesthetic. We demonstrate
      this method for Indo-Pacific lionfish (Pterois volitans/P. miles), species which
      are particularly vulnerable to barotrauma when transported to and handled at the
      surface. To test our method, we tagged 161 individuals inhabiting 26 coral reef
      locations in the Bahamas over a period of 3 years. Our method resulted in no
      instances of barotrauma, reduced handling and recovery time, and minimal post
      tagging release displacement compared with conventional ex situ tag application.
      Opportunistic resighting and recapture of tagged individuals reveals that
      lionfish exhibit highly variable site fidelity, movement patterns, and growth
      rates on invaded coral reef habitats. In total, 24% of lionfish were resighted
      between 29 and 188 days after tagging. Of these, 90% were located at the site of
      capture, while the remaining individuals were resighted between 200 m and 1.1 km
      from initial site of capture over 29 days later. In situ growth rates ranged
      between 0.1 and 0.6 mm/day. While individuals tagged with streamer tags posted
      slower growth rates with increasing size, as expected, there was no relationship
      between growth rate and fish size for individuals marked with dart tags,
      potentially because of large effects of tag presence on the activities of small
      bodied lionfish (i.e., <150 mm), where the tag was up to 7.6% of the lionfish's
      mass. Our study offers a novel in situ tagging technique that can be used to
      provide critical information on fish site fidelity, movement patterns, and growth
      in cases where ex situ tagging is not feasible. 

PMID- 25614792
TI  - Reliable molecular identification of nine tropical whitefly species.
AB  - The identification of whitefly species in adult stage is problematic.
      Morphological differentiation of pupae is one of the better methods for
      determining identity of species, but it may vary depending on the host plant on
      which they develop which can lead to misidentifications and erroneous naming of
      new species. Polymerase chain reaction (PCR) fragment amplified from the
      mitochondrial cytochrome oxidase I (COI) gene is often used for mitochondrial
      haplotype identification that can be associated with specific species. Our
      objective was to compare morphometric traits against DNA barcode sequences to
      develop and implement a diagnostic molecular kit based on a RFLP-PCR method using
      the COI gene for the rapid identification of whiteflies. This study will allow
      for the rapid diagnosis of the diverse community of whiteflies attacking plants
      of economic interest in Colombia. It also provides access to the COI sequence
      that can be used to develop predator conservation techniques by establishing
      which predators have a trophic linkage with the focal whitefly pest species. 

PMID- 25614793
TI  - European red squirrel population dynamics driven by squirrelpox at a gray
      squirrel invasion interface.
AB  - Infectious disease introduced by non-native species is increasingly cited as a
      facilitator of native population declines, but direct evidence may be lacking due
      to inadequate population and disease prevalence data surrounding an outbreak.
      Previous indirect evidence and theoretical models support squirrelpox virus
      (SQPV) as being potentially involved in the decline of red squirrels (Sciurus
      vulgaris) following the introduction of the non-native gray squirrel (Sciurus
      carolinensis) to the United Kingdom. The red squirrel is a major UK conservation
      concern and understanding its continuing decline is important for any attempt to
      mitigate the decline. The red squirrel-gray squirrel system is also exemplary of
      the interplay between infectious disease (apparent competition) and direct
      competition in driving the replacement of a native by an invasive species. Time
      series data from Merseyside are presented on squirrel abundance and squirrelpox
      disease (SQPx) incidence, to determine the effect of the pathogen and the non
      native species on the native red squirrel populations. Analysis indicates that
      SQPx in red squirrels has a significant negative impact on squirrel densities and
      their population growth rate (PGR). There is little evidence for a direct gray
      squirrel impact; only gray squirrel presence (but not density) proved to
      influence red squirrel density, but not red squirrel PGR. The dynamics of red
      SQPx cases are largely determined by previous red SQPx cases, although previous
      infection of local gray squirrels also feature, and thus, SQPV-infected gray
      squirrels are identified as potentially initiating outbreaks of SQPx in red
      squirrels. Retrospective serology indicates that approximately 8% of red
      squirrels exposed to SQPV may survive infection during an epidemic. This study
      further highlights the UK red squirrel - gray squirrel system as a classic
      example of a native species population decline strongly facilitated by infectious
      disease introduced by a non-native species. It is therefore paramount that
      disease prevention and control measures are integral in attempts to conserve red
      squirrels in the United Kingdom. 

PMID- 25614794
TI  - Higher mobility of butterflies than moths connected to habitat suitability and
      body size in a release experiment.
AB  - Mobility is a key factor determining lepidopteran species responses to
      environmental change. However, direct multispecies comparisons of mobility are
      rare and empirical comparisons between butterflies and moths have not been
      previously conducted. Here, we compared mobility between butterflies and diurnal
      moths and studied species traits affecting butterfly mobility. We experimentally
      marked and released 2011 butterfly and 2367 moth individuals belonging to 32 and
      28 species, respectively, in a 25 m * 25 m release area within an 11-ha, 8-year
      old set-aside field. Distance moved and emigration rate from the release habitat
      were recorded by species. The release experiment produced directly comparable
      mobility data in 18 butterfly and 9 moth species with almost 500 individuals
      recaptured. Butterflies were found more mobile than geometroid moths in terms of
      both distance moved (mean 315 m vs. 63 m, respectively) and emigration rate (mean
      54% vs. 17%, respectively). Release habitat suitability had a strong effect on
      emigration rate and distance moved, because butterflies tended to leave the set
      aside, if it was not suitable for breeding. In addition, emigration rate and
      distance moved increased significantly with increasing body size. When
      phylogenetic relatedness among species was included in the analyses, the
      significant effect of body size disappeared, but habitat suitability remained
      significant for distance moved. The higher mobility of butterflies than
      geometroid moths can largely be explained by morphological differences, as
      butterflies are more robust fliers. The important role of release habitat
      suitability in butterfly mobility was expected, but seems not to have been
      empirically documented before. The observed positive correlation between
      butterfly size and mobility is in agreement with our previous findings on
      butterfly colonization speed in a long-term set-aside experiment and recent meta
      analyses on butterfly mobility. 

PMID- 25614795
TI  - Evidence of local short-distance spawning migration of tropical freshwater eels,
      and implications for the evolution of freshwater eel migration.
AB  - Freshwater eels have fascinated biologists for centuries due to the spectacular
      long-distance migrations between the eels' freshwater habitats and their spawning
      areas far out in the ocean and the mysteries of their ecology. The spawning areas
      of Atlantic eels and Japanese eel were located far offshore in the Atlantic Ocean
      and the Pacific Ocean, respectively, and their reproduction took place thousands
      of kilometers away from their growth habitats. Phylogenetic studies have revealed
      that freshwater eels originated in the Indonesian region. However, remarkably
      little is known about the life histories of tropical freshwater eels despite the
      fact that tropical eels are key to understanding the nature of primitive forms of
      catadromous migration. This study found spawning-condition tropical freshwater
      eels in Lake Poso, central Sulawesi, Indonesia, with considerably high
      gonadosomatic index values and with histologically fully developed gonads. This
      study provides the first evidence that under certain conditions, freshwater eels
      have conditions that are immediately able to spawn even in river downstream. The
      results suggest that, in contrast to the migrations made by the Atlantic and
      Japanese eels, freshwater eels originally migrated only short distances of <100
      kilometers to local spawning areas adjacent to their freshwater growth habitats.
      Ancestral eels most likely underwent a catadromous migration from local short
      distance movements in tropical coastal waters to the long-distance migrations
      characteristic of present-day temperate eels, which has been well established as
      occurring in subtropical gyres in both hemispheres. 

PMID- 25614796
TI  - Demographic variation in the U.K. serotine bat: filling gaps in knowledge for
      management.
AB  - Species of conservation concern, or those in conflict with man, are most
      efficiently managed with an understanding of their population dynamics. European
      bats exemplify the need for successful and cost-effective management for both
      reasons, often simultaneously. Across Europe, bats are protected, and the concept
      of Favourable Conservation Status (FCS) is used as a key tool for the assessment
      and licensing of disruptive actions to populations. However, for efficient
      decision-making, this assessment requires knowledge on the demographic rates and
      long-term dynamics of populations. We used capture-mark-recapture to describe
      demographic rates for the Serotine bat (Eptesicus serotinus) at two sites in
      England and investigate the transition rates between three stages: juveniles,
      immatures, and breeders. We then use these rates in an individual-based
      population dynamics model to investigate the expected trajectories for both
      populations. Our results demonstrate for the first time the presence and scale of
      temporal variation in this species' demography. We describe the lengthy
      prereproductive period (3.5 years) that female Serotines experience. Finally, we
      show how site-specific variation in demographic rates can produce divergent
      population trajectories. Effective management of European bat populations can be
      achieved through the understanding of life histories, and local demographic rates
      and population dynamics, in order to anticipate the presence of source and sink
      sites in the landscape. Using the Serotine bat in England, we show that these can
      be obtained from rigorous and systematic studies of long-term demographic
      datasets. 

PMID- 25614797
TI  - Non-serotinous woody plants behave as aerial seed bank species when a late-summer
      wildfire coincides with a mast year.
AB  - ABSTRACT: Trees which lack obvious fire-adaptive traits such as serotinous seed
      bearing structures or vegetative resprouting are assumed to be at a dramatic
      disadvantage in recolonization via sexual recruitment after fire, because seed
      dispersal is invariably quite constrained. We propose an alternative strategy in
      masting tree species with woody cones or cone-like structures: that the large
      clusters of woody tissue in a mast year will sufficiently impede heat transfer
      that a small fraction of seeds can survive the flaming front passage; in a mast
      year, this small fraction would be a very large absolute number.In Kootenay
      National Park in British Columbia, we examined regeneration by Engelmann spruce
      (Picea engelmannii), a non-serotinous conifer, after two fires, both of which
      coincided with mast years. Coupling models of seed survivorship within cones and
      seed maturation schedule to a spatially realistic recruitment model, we show that
      (1) the spatial pattern of seedlings on a 630 m transect from the forest edge
      into the burn was best explained if there was in situ seed dissemination by burnt
      trees; (2) in areas several hundred meters from any living trees, recruitment
      density was well correlated with local prefire cone density; and (3) spruce was
      responding exactly like its serotinous codominant, lodgepole pine (Pinus
      contorta).We conclude that non-serotinous species can indeed behave like aerial
      seed bank species in mast years if the fire takes place late in the seed
      maturation period. Using the example of the circumpolar boreal forest, while the
      joint probability of a mast year and a late-season fire will make this type of
      event rare (we estimate P = 0.1), nonetheless, it would permit a species lacking
      obvious fire-adapted traits to occasionally establish a widespread and abundant
      cohort on a large part of the landscape.

PMID- 25614798
TI  - Dispersal and spatial heterogeneity allow coexistence between enemies and
      protective mutualists.
AB  - Protective mutualisms, where a symbiont reduces the negative effects of another
      species on a shared host, represent a common type of species interaction in
      natural communities, yet it is still unclear what ecological conditions might
      favor their emergence. Studies suggest that the initial evolution of protective
      mutualists might involve closely related pathogenic variants with similar life
      histories, but different competitive abilities and impacts on host fitness. We
      derive a model to evaluate this hypothesis and show that, in general, a
      protective variant cannot spread from rarity or exclude a more pathogenic strain.
      While the conditions allowing mutualist invasion are more likely with increased
      environmental productivity, they still depend on initial densities in the invaded
      patch exceeding a threshold, highlighting the likely importance of spatial
      structure and demographic stochasticity. Using a numerical simulation approach,
      we show that regional coexistence is in fact possible in an explicitly spatial
      system and that, under some circumstances, the mutualist population can exclude
      the enemy. More broadly, the establishment of protective mutualists may be
      favored when there are other life-history differences from more pathogenic
      symbionts, such as vertical transmission or additional direct benefits to hosts. 

PMID- 25614799
TI  - Interacting effects of age, density, and weather on survival and current
      reproduction for a large mammal.
AB  - Individual-based study of natural populations allows for accurate and precise
      estimation of fitness components and the extent to which they might vary with
      ecological conditions. By tracking the fates of all 701 horses known to have
      lived on Sable Island, Canada, from 2009 to 2013 (where there is no predation,
      human interference, or interspecific competition for food), we present a detailed
      analysis of structured population dynamics with focus on interacting effects of
      intraspecific competition and weather on reproduction and survival. Annual
      survival of adult females (0.866 +/- 0.107 [[Formula: see text] +/- SE]) was
      lower than that of 3-year-olds (0.955 +/- 0.051), although annual fecundity
      (producing a foal in a year that was observed during our census) was higher in
      adults (0.616 +/- 0.023) compared to 3-year-olds (0.402 +/- 0.054). Milder
      winters and lower densities during gestation increased fecundity. Density
      negatively impacted survival for all age and sex categories; however, highest
      adult female survival was observed during high-density years coupled with a harsh
      winter, the result expected if pregnancy loss during winter or loss of foals in
      spring improved survival. Three-year-old females, which reproduced at lower
      rates, experienced higher survival than adults. Our results contrast with a
      previous study of feral horses that suggested recently feral ungulates might be
      artificially selected to reproduce even when costs to survival are high. In part,
      this may be because of the comparably long history of feralization (250 years; at
      least 25 generations) for Sable Island horses. 

PMID- 25614800
TI  - Desert salt flats as oases for the spider Saltonia incerta Banks (Araneae:
      Dictynidae).
AB  - The deserts of southwestern North America have undergone dramatic changes over
      their recent geological history including large changes in size and connectivity
      during the Pleistocene glaciopluvial cycles. This study examines the population
      history of the rare spider Saltonia incerta, once thought to be extinct, to
      determine the role of past climatological events in shaping the structure of the
      species. This species is restricted to salt crusts of intermittent or dry lakes,
      streams or rivers in the desert southwest, a region that was much wetter during
      glacial periods. We examine the distribution and genetic variability of
      populations to test whether there is recent dispersal throughout the range of the
      species. Analyses of mitochondrial and nuclear DNA indicate significant
      population structure, with one major clade comprising New Mexico localities and
      one comprising California-northern Baja California localities. Finer-scale
      structure is evident within the California clade, although not all of the
      subclades are reciprocally monophyletic. However, isolation with migration
      analysis suggests that migration is very low to non-existent. These results
      extend the known distribution of Saltonia, provide genetic evidence of strong
      isolation among localities within drainage basins and between drainage basins and
      provide a mechanistic understanding of population connectivity after the
      aridification of the American southwest. The implication is that although the
      species' distribution has been fragmented, populations have persisted throughout
      this area, suggesting that desert salt flats may have served as refugia for at
      least some terrestrial species. 

PMID- 25614803
TI  - Case reports as a resource for teaching and learning.

PMID- 25614802
TI  - The systematic study of circulating tumor cell isolation using lithographic
      microfilters.
AB  - Circulating tumor cells (CTCs) disseminated into peripheral blood from a primary,
      or metastatic, tumor can be used for early detection, diagnosis and monitoring of
      solid malignancies. CTC isolation by size exclusion techniques have long
      interested researchers as a simple broad based approach, which is
      methodologically diverse for use in both genomic and protein detection platforms.
      Though a variety of these microfiltration systems are employed academically and
      commercially, the limited ability to easily alter microfilter designs has
      hindered the optimization for CTC capture. To overcome this problem, we studied a
      unique photo-definable material with a scalable and mass producible
      photolithographic fabrication method. We use this fabrication method to
      systematically study and optimize the parameters necessary for CTC isolation
      using a microfiltration approach, followed by a comparison to a "standard"
      filtration membrane. We demonstrate that properly designed microfilters can
      capture MCF-7 cancer cells at rate of 98 +/- 2% if they consist of uniform
      patterned distributions, >=160 000 pores, and 7 MUm pore diameters.

PMID- 25614804
TI  - Molecular characteristics of residual cancer and stromal cells after
      chemoradiotherapy for gastric cancer: report of four cases.
AB  - KEY CLINICAL MESSAGE: Four patients with gastric cancer underwent 5-fluorouracil
      and cisplatin-based chemoradiotherapy followed by surgery. Expression analysis of
      chemoradiosensitivity related genes in residual cancer using formalin-fixed
      paraffin-embedded specimens may be useful when determining a chemotherapy regimen
      for disease recurrence after chemoradiotherapy for gastric cancer.

PMID- 25614805
TI  - Long-term survival in multiple myeloma.
AB  - KEY CLINICAL MESSAGE: The survival of multiple myeloma patients has improved very
      significantly over the last decade. Still median overall survival is inferior to
      5 years. A small proportion of patients survive longer than 10 years. In this
      paper we discuss four cases illustrating the nonhomogeneous clinical presentation
      and evolution of this subset of patients. Surprisingly, these long survivors do
      not always have deep responses and some require frequent treatments, which
      include autologous stem cell transplantation and novel drugs. The authors discuss
      several aspects of these clinical histories, including treatment options, raising
      hypothesis on their relation with long survivorship which may be important to
      have in consideration when studying this subject.

PMID- 25614806
TI  - A worn Bjork-Shiley prosthetic valve without valve dysfunction observed during
      ascending aortic replacement.
AB  - KEY CLINICAL MESSAGE: The implanted first-generation Bjork-Shiley valve in our
      patient was functioning well before aortic surgery, but we replaced the valve
      because we confirmed disc erosion 39 years after implantation during the surgery.
      We judged that the implanted valve was no longer capable of maintaining the
      patient's life.

PMID- 25614807
TI  - Upper limb erythema nodosum: the first presentation of Crohn's disease.
AB  - KEY CLINICAL MESSAGE: Inflammatory bowel disease can present with extraintestinal
      features as the patient's only complaint. The erythema nodosum (EN) initially
      affected the upper limbs only, reminding us that signs do not always present in a
      classical fashion. The presence of EN should prompt the clinician to look for any
      underlying cause.

PMID- 25614808
TI  - Acute appendicitis caused by acute myeloid leukemia.
AB  - KEY CLINICAL MESSAGE: A case of appendiceal involvement by acute myeloid leukemia
      (AML) in an adult with recent history of AML transformed from myelodysplastic
      syndrome (MDS) was presented. Being aware of this rare presentation in particular
      in a patient with history of MDS and/or AML is important for prompt clinical
      diagnosis and management.

PMID- 25614809
TI  - Embolization of a left uterine artery mycotic aneurysm after a neglected,
      perforated appendicitis before delivery.
AB  - KEY CLINICAL MESSAGE: We report a case of a successful embolization of a mycotic
      aneurysm of the left uterine artery in the puerperium after a neglected
      perforated appendicitis. A mycotic aneurysm, meaning an infection of the vessel
      wall which leads to an aneurysmatic dilatation of the vessel, is potentially life
      threatening if rupture occurs.

PMID- 25614810
TI  - Severe Leptospira interrogans serovar Icterohaemorrhagiae infection with hepato
      renal-pulmonary involvement treated with corticosteroids.
AB  - KEY CLINICAL MESSAGE: The traditional concept of immediate antibiotic treatment
      in suspected leptospirosis seems to be especially important for patients up to
      day 4 of clinical illness. As immune mechanisms probably play a crucial role in
      advanced leptospirosis with presumed pulmonary hemorrhages, patients might
      benefit from corticosteroids or other immunosuppressive agents beside
      antibiotics.

PMID- 25614811
TI  - Gastrointestinal stromal tumor (GIST) mistaken for pancreatic pseudocyst - case
      report and literature review.
AB  - KEY CLINICAL MESSAGE: A 74-year-old female patient underwent a Roux-en-Y
      cystjejunostomy for pancreatic pseudocyst developed several melena episodes and
      she was surgically reappraised. The main diagnostic concern was a pancreatic
      cystic neoplasm. A 12 * 8.0 * 5.0 cm retro-gastric lesion was resected and
      pathology report indicated an unsuspected gastrointestinal stromal tumor (GIST).
      The report aimed to describe an atypical presentation of GIST.

PMID- 25614813
TI  - Pulmonary squamous cell carcinoma and sorafenib.
AB  - KEY CLINICAL MESSAGE: Pulmonary squamous cell carcinomas are not often thought to
      sensitive to targeted agents, like their cousin the adenocarcinoma of the lung.
      With appropriate testing of molecular markers, squamous cell carcinomas, like
      adenocarcinomas of the lung, melanomas, and renal cell carcinomas, may be found
      to be sensitive to newer, targeted agents.

PMID- 25614812
TI  - Distal trisomy 10q syndrome, report of a patient with duplicated q24.31 - qter,
      autism spectrum disorder and unusual features.
AB  - KEY CLINICAL MESSAGE: We report on a patient with distal trisomy 10q syndrome
      presenting with a few previously undescribed physical features, as well as,
      autism spectrum disorder (ASD). We recommend that patients with distal trisomy
      10q syndrome should have a behavioral evaluation for ASD for the early
      institution of therapy.

PMID- 25614814
TI  - Cutaneous lymphocyte antigen expression loss and PD1 positivity in early
      cutaneous lesions of rapidly progressive mycosis fungoides.
AB  - KEY CLINICAL MESSAGE: It's important to assess cases both clinically and
      pathologically for factors potentially predictive of an aggressive clinical
      course. We concluded that the relative immunosuppressive effects of PD1 may
      contribute to tumor progression while the lack of staining for cutaneous
      lymphocyte antigen may be an additional factor facilitating distant
      extracutaneous migration.

PMID- 25614815
TI  - Prolonged survival in metastatic colorectal cancer following chemotherapy.
AB  - KEY CLINICAL MESSAGE: The cost of treating metastatic colorectal cancer has
      increased significantly after the introduction of targeted antivascular
      therapies. We report the unusual case of a patient with colorectal cancer with
      several large liver metastases at diagnosis, who was cured after removal of the
      primary tumor and treatment with 5-FU/LV only.

PMID- 25614816
TI  - A case of Barber-Say syndrome in a male Japanese newborn.
AB  - KEY CLINICAL MESSAGE: We reported a case of Barber-Say syndrome (BSS) in a
      Japanese newborn. Distinctive features of BSS were found; macrostomia, gingival
      dysplasia, cup-shaped low-set ears, wrinkling redundant skin, and hypertrichosis.
      Fundus showed subretinal drusenoid deposits, a novel finding of BSS. Genetic
      analysis is underway using next-generation genome sequencing and microarray
      analysis.

PMID- 25614817
TI  - Cognitive evolutionary therapy for depression: a case study.
AB  - KEY CLINICAL MESSAGE: We present an evolutionary-driven cognitive-behavioral
      intervention for a moderately depressed patient. Standard cognitive and
      behavioral therapy techniques focused on the patient's perfectionistic and self
      downing beliefs, while novel, evolutionary-informed techniques were used to guide
      behavioral activation and conceptualize secondary emotional problems related to
      anger. The treatment reduced depressive symptomatology and increased evolutionary
      fitness.

PMID- 25614818
TI  - Snapshots in surgery: incidentally discovered cryptorchidism.
AB  - KEY CLINICAL MESSAGE: An 18-year-old was presented with a large inflamed appendix
      (compressed by the instrument) and a spermatic cord with right undescended
      testicle (cryptorchidism). Patients who undergo orchiopexy after age 12 years, or
      no orchiopexy, are 2-6 times as likely to have testicular cancer as those who
      undergo prepubertal orchiopexy.

PMID- 25614819
TI  - Leishmania donovani bodies in bone marrow.
AB  - KEY CLINICAL MESSAGE: We report a case of a 5-year-old female, resident of
      Afghanistan, who presented with fever and massive splenomegaly. Bone marrow
      revealed Leishmania donovani bodies (LD bodies) in macrophages characterized by a
      kinetoplast and characteristic double dot appearance. She was diagnosed as
      visceral leishmaniasis which is transmitted by sandflies (Phlebotomus).

PMID- 25614822
TI  - Ipilimumab-induced autoimmune hypophysitis: a differential for sellar mass
      lesions.
AB  - Autoimmune hypophysitis (AH) has been previously described in a typical
      demographic population, primarily women in the reproductive age group and
      perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte
      associated antigen 4 biological therapy (ipilimumab) against advanced cancers
      like metastatic melanomas has now resulted in a new form of hypophysitis being
      increasingly recognised under a spectrum of immune-related adverse events. Drug
      related AH often presents with subtle symptoms and a pituitary mass, with the
      potential for fatality necessitating wide awareness and a high index of clinical
      suspicion given that it is usually treatable. We describe below two cases of AH
      within the last three months at our centre, which were treated with different
      regimens and produced good endocrine outcomes. LEARNING POINTS: AH is a new and
      defined clinical entity occurring as a side effect of ipilimumab, which enhances
      immune-mediated destruction of metastatic melanoma.It can present insidiously and
      have life-threatening complications related to hypocortisolism, hence a high
      index of clinical suspicion must be exerted by treating physicians, and seems to
      result in resolution of pituitary masses and variable improvements of pituitary
      function.Clinical improvement, radiological resolution of pituitary masses and
      variable normalisation of pituitary function are possible with early treatment
      with high-dose oral or i.v. steroids and hormone replacement therapy, although
      duration and dosing protocols are unclear at this stage.Ipilimumab should
      continue to be prescribed as treatment for metastatic melanoma; however, close
      clinical observation of patient's progress must be maintained while they are on
      this drug.Predictive factors for onset of AH remain unclear and it is imperative
      that AH is distinguished from pituitary metastases.Further studies are required
      to determine the safety of continuing therapy with ipilimumab in patients who
      have developed AH while on treatment.

PMID- 25614821
TI  - Combined immune checkpoint protein blockade and low dose whole body irradiation
      as immunotherapy for myeloma.
AB  - BACKGROUND: Multiple myeloma is characterized by the presence of transformed
      neoplastic plasma cells in the bone marrow and is generally considered to be an
      incurable disease. Successful treatments will likely require multi-faceted
      approaches incorporating conventional drug therapies, immunotherapy and other
      novel treatments. Our lab previously showed that a combination of transient
      lymphodepletion (sublethal whole body irradiation) and PD-1/PD-L1 blockade
      generated anti-myeloma T cell reactivity capable of eliminating established
      disease. We hypothesized that blocking a combination of checkpoint receptors in
      the context of low-dose, lymphodepleting whole body radiation would boost anti
      tumor immunity. METHODS: To test our central hypothesis, we utilized a 5T33
      murine multiple myeloma model. Myeloma-bearing mice were treated with a low dose
      of whole body irradiation and combinations of blocking antibodies to PD-L1, LAG
      3, TIM-3, CD48 (the ligand for 2B4) and CTLA4. RESULTS: Temporal phenotypic
      analysis of bone marrow from myeloma-bearing mice demonstrated that elevated
      percentages of PD-1, 2B4, LAG-3 and TIM-3 proteins were expressed on T cells.
      When PD-L1 blockade was combined with blocking antibodies to LAG-3, TIM-3 or
      CTLA4, synergistic or additive increases in survival were observed (survival
      rates improved from ~30% to >80%). The increased survival rates correlated with
      increased frequencies of tumor-reactive CD8 and CD4 T cells. When stimulated in
      vitro with myeloma cells, CD8 T cells from treated mice produced elevated levels
      proinflammatory cytokines. Cytokines were spontaneously released from CD4 T cells
      isolated from mice treated with PD-L1 plus CTLA4 blocking antibodies.
      CONCLUSIONS: These data indicate that blocking PD-1/PD-L1 interactions in
      conjunction with other immune checkpoint proteins provides synergistic anti-tumor
      efficacy following lymphodepletive doses of whole body irradiation. This strategy
      is a promising combination strategy for myeloma and other hematologic
      malignancies.

PMID- 25614823
TI  - Thyrotoxicosis with absence of clinical features of acromegaly in a TSH- and GH
      secreting, invasive pituitary macroadenoma.
AB  - A 54-year-old woman presented with bi-temporal hemianopia, palpitations, and
      diaphoresis. An invasive pituitary macroadenoma was discovered. The patient had
      biochemical evidence of secondary hyperthyroidism and GH excess; however, she did
      not appear to be acromegalic. Surgical removal of the pituitary mass revealed a
      plurihormonal TSH/GH co-secreting pituitary adenoma. TSH-secreting adenomas can
      co-secrete other hormones including GH, prolactin, and gonadotropins; conversely,
      co-secretion of TSH from a pituitary adenoma in acromegaly is infrequent.
      LEARNING POINTS: This case highlights an unusual patient with a rare TSH/GH co
      secreting pituitary adenoma with absence of the clinical features of
      acromegaly.Plurihormonality does not always translate into the clinical features
      of hormonal excess.There appears to be a clinical and immunohistochemical
      spectrum present in plurihormonal tumors.

PMID- 25614824
TI  - Suspension of basal insulin to avoid hypoglycemia in type 1 diabetes treated with
      insulin pump.
AB  - Treatment with continuous s.c. insulin infusion (CSII) provides better glycemic
      control and lower risk of hypoglycemia than conventional therapy with multiple
      daily insulin injections. These benefits have been related to a more reliable
      absorption and an improved pharmacokinetic profile of insulin delivered through
      CSII therapy. However, even for patients treated with CSII, exaggerated postmeal
      hyperglycemic excursions and late postabsorptive hypoglycemia can still
      constitute a therapeutic challenge. Two female patients with type 1 diabetes who
      began treatment with CSII required to increase their previous breakfast insulin
      to-carbohydrate ratio in order to achieve postprandial glycemic goals. However,
      they simultaneously presented recurrent episodes of late hypoglycemia several
      hours after breakfast bolus. Advancing the timing of the bolus was ineffective
      and bothersome for patients. In both cases, the best therapeutic option was to
      set a basal insulin rate of zero units per hour during 6 h after breakfast. Even
      so, they need to routinely take a midmorning snack with 10-20 g of carbohydrates
      to avoid late postabsorptive hypoglycemia. They have been using this insulin
      schedule for about 3 years without complications. The action of prandial insulin
      delivered through insulin pumps can be inappropriately delayed for the
      requirements of some patients. Although suspension of basal rate can be an
      acceptable therapeutic alternative for them, these cases demonstrate that new
      strategies to improve the bioavailability of prandial insulin infused through
      CSII are still needed. LEARNING POINTS: CSII remains the most physiologically
      suitable system of insulin delivery available today.Additionally, the duration of
      action of prandial insulin delivered through insulin pumps can be excessively
      prolonged in some patients with type 1 diabetes.These patients can present
      recurrent late episodes of hypoglycemia several hours after the administration of
      insulin boluses.The routine suspension of basal insulin for several hours,
      leaving meal bolus to cover both prandial and basal insulin requirements, can be
      a therapeutic option for these subjects.

PMID- 25614825
TI  - An unusual case of an ACTH-secreting macroadenoma with a germline variant in the
      aryl hydrocarbon receptor-interacting protein (AIP) gene.
AB  - A patient of Cushing's disease (CD) characterized by a large tumor and only
      subtle symptoms of hormonal hypersecretion was examined. The patient had a
      germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene.
      A 50-year-old male presenting with headache was diagnosed with a large pituitary
      tumor by magnetic resonance imaging (MRI). His visual fields were intact and he
      exhibited no features of CD. Owing to an exuberant response to synacthen, an
      overnight dexamethasone suppression test was performed revealing inadequate
      suppression of plasma cortisol (419 nmol/l). Owing to tumor growth and visual
      field impairment, he underwent transsphenoidal surgery and developed
      hypocortisolemia. The pathology specimen revealed a sparsely granulated
      corticotrope adenoma. Postoperative MRI showed a large tumor remnant. The patient
      developed skin hyperpigmentation and a synacthen test demonstrated high basal and
      stimulated cortisol levels; an overnight dexamethasone suppression test showed no
      suppression (791 nmol/l) and elevated plasma ACTH levels (135 ng/l). A
      transcranial operation was performed followed by radiotherapy. Two months after
      radiotherapy, he developed secondary adrenocortical failure. Genetic testing
      revealed an AIP variant of unknown significance (p.R16H) without loss of the
      normal AIP allele in the tumor. A literature review showed ten CD patients with
      AIP gene variants, of whom five (including our case) were p.R16H. CD is
      occasionally dominated by pituitary tumor growth rather than symptoms of
      hypersecretion. The particular AIP gene variant identified in our patient is
      shared by four other reported cases of CD. Future studies are needed to assess
      whether the reported AIP gene variant is more than just coincidental. LEARNING
      POINTS: CD is occasionally dominated by pituitary tumor growth rather than
      symptoms of hypersecretion.Resolution of both tumor remnant and hormonal
      hypersecretion may occur within 2 months after postoperative radiotherapy.The
      particular AIP gene variant identified in our patient is shared by four other
      reported cases of CD.

PMID- 25614826
TI  - Liquid Phase adsorption kinetics and equilibrium of toluene by novel modified
      diatomite.
AB  - The adsorption equilibria of toluene from aqueous solutions on natural and
      modified diatomite were examined at different operation parameters such as pH,
      contact time, initial toluene concentration was evaluated and optimum
      experimental conditions were identified. The surface area and morphology of the
      nanoparticles were characterized by SEM, BET, XRD, FTIR and EDX analysis. It was
      found that in order to obtain the highest possible removal of toluene, the
      experiments can be carried out at pH 6, temperature 25 degrees C, an agitation
      speed of 200 rpm, an initial toluene concentration of 150 mg/L, a centrifugal
      rate of 4000 rpm, adsorbent dosage = 0.1 g and a process time of 90 min. The
      results of this work show that the maximum percentage removal of toluene from
      aqueous solution in the optimum conditions for NONMD was 96.91% (145.36 mg/g).
      Furthermore, under same conditions, the maximum adsorption of natural diatomite
      was 71.45% (107.18 mg/g). Both adsorption kinetic and isotherm experiments were
      carried out. The experimental data showed that the adsorption follows the
      Langmuir model and Freundlich model on natural and modified diatomite
      respectively. The kinetics results were found to conform well to pseudo-second
      order kinetics model with good correlation. Thus, this study demonstrated that
      the modified diatomite could be used as potential adsorbent for removal of
      toluene from aqueous solution. 

PMID- 25614827
TI  - Novel Arsenic Nanoparticles Are More Effective and Less Toxic than As (III) to
      Inhibit Extracellular and Intracellular Proliferation of Leishmania donovani.
AB  - Visceral leishmaniasis, a vector-borne tropical disease that is threatening about
      350 million people worldwide, is caused by the protozoan parasite Leishmania
      donovani. Metalloids like arsenic and antimony have been used to treat diseases
      like leishmaniasis caused by the kinetoplastid parasites. Arsenic (III) at a
      relatively higher concentration (30 MUg/mL) has been shown to have
      antileishmanial activity, but this concentration is reported to be toxic in
      several experimental mammalian systems. Nanosized metal (0) particles have been
      shown to be more effective than their higher oxidation state forms. There is no
      information so far regarding arsenic nanoparticles (As-NPs) as an antileishmanial
      agent. We have tested the antileishmanial properties of the As-NPs, developed for
      the first time in our laboratory. As-NPs inhibited the in vitro growth, oxygen
      consumption, infectivity, and intramacrophage proliferation of L. donovani
      parasites at a concentration which is about several fold lower than that of As
      (III). Moreover, this antileishmanial activity has comparatively less cytotoxic
      effect on the mouse macrophage cell line. It is evident from our findings that As
      NPs have more potential than As (III) to be used as an antileishmanial agent. 

PMID- 25614828
TI  - Posterior pole sparing laser photocoagulation combined with intravitreal
      bevacizumab injection in posterior retinopathy of prematurity.
AB  - Purpose. To report the results of the posterior pole sparing laser
      photocoagulation combined with intravitreal bevacizumab injection (IVB) in
      retinopathy of prematurity (ROP). Methods. A retrospective chart review of
      premature babies with ROP, all of whom received laser photocoagulation with IVB.
      Eleven eyes of 6 infants with advanced zone I ROP underwent laser ablation
      sparing posterior pole with concurrent IVB. The results were compared with those
      of full-laser treatment combined with IVB to 8 eyes of 5 infants with advanced
      ROP without involvement of the posterior pole. Results. The posterior pole
      sparing laser with IVB was performed with zone I, stage 3+ ROP at the mean
      postmenstrual age of 36 weeks and 5 days. The plus sign decreased significantly
      at postoperative day 1, the neovascular proliferation regressed by postoperative
      week 1, and the normal vascularization started at postoperative day 32 on the
      average. Two months after treatment, vascularization of the spared avascular area
      was completed. There was no macular dragging, tractional retinal detachment,
      foveal destruction by laser scars, or any other adverse event. No significant
      anatomical differences were identified from those of full-laser ablation combined
      with IVB. Conclusions. Posterior pole sparing laser with IVB can give favorable
      results without destruction of posterior pole retina. 

PMID- 25614829
TI  - Immobilization of Aspergillus niger F7-02 Lipase in Polysaccharide Hydrogel Beads
      of Irvingia gabonensis Matrix.
AB  - The potential of polysaccharide Irvingia gabonensis matrix as enzyme
      immobilization support was investigated. Lipase of Aspergillus niger F7-02 was
      immobilized by entrapment using glutaraldehyde as the cross-linking agent and
      stabilized in ethanolic-formaldehyde solution. The pH and temperature stability
      and activity yield of the immobilized enzyme were determined. Such parameters as
      enzyme load, bead size, number of beads, and bead reusability were also
      optimized. Adequate gel strength to form stabilized beads was achieved at 15.52%
      (w/v) Irvingia gabonensis powder, 15% (v/v) partially purified lipase, 2.5% (v/v)
      glutaraldehyde, and 3 : 1 (v/v) ethanolic-formaldehyde solution. There was 3.93
      fold purification when the crude enzyme was partially purified in two-step
      purification using Imarsil and activated charcoal. Optimum lipase activity 75.3
      Ug(-1) was achieved in 50 mL test solution containing 15 beads of 7 mm bead size.
      Relative activity 80% was retained at eight repeated cycles. The immobilization
      process gave activity yield of 59.1% with specific activity of 12.3 Umg(-1) and
      stabilized at optimum pH 4.5 and temperature 55 degrees C. Thus the effectiveness
      and cost-efficiency of I. gabonensis as a polymer matrix for lipase
      immobilization have been established. 

PMID- 25614830
TI  - Patient perception of ideal body weight and the effect of body mass index.
AB  - OBJECTIVE: Despite much effort, obesity remains a significant public health
      problem. One of the main contributing factors is patients' perception of their
      target ideal body weight. This study aimed to assess this perception. METHODS:
      The study took place in an urban area, with the majority of participants in the
      study being Hispanic (65.7%) or African-American (28.0%). Patients presented to
      an outpatient clinic were surveyed regarding their ideal body weight and their
      ideal BMI calculated. Subsequently they were classified into different categories
      based on their actual measured BMI. Their responses for ideal BMI were compared.
      RESULTS: In 254 surveys, mean measured BMI was 31.71 +/- 8.01. Responses to ideal
      BMI had a range of 18.89-38.15 with a mean of 25.96 +/- 3.25. Mean (+/-SD) ideal
      BMI for patients with a measured BMI of <18.5, 18.5-24.9, 25-29.9, and >=30 was
      20.14 +/- 1.46, 23.11 +/- 1.68, 25.69 +/- 2.19, and 27.22 +/- 3.31, respectively.
      These differences were highly significant (P < 0.001, ANOVA). CONCLUSIONS: Most
      patients had an inflated sense of their target ideal body weight. Patients with
      higher measured BMI had higher target numbers for their ideal BMI. Better
      education of patients is critical for obesity prevention programs.

PMID- 25614831
TI  - Prevalence and severity of anaemia stratified by age and gender in rural India.
AB  - Anaemia is a major public health problem in India. Although nearly three quarters
      of the Indian population live in rural areas, the epidemiology of anaemia in
      rural settings is not well known. We performed a retrospective observational
      study using routine clinical data from patients attending the out-patient clinics
      of a rural hospital in India from June 2011 to August 2014. The study included
      73,795 determinations of haemoglobin. 49.5% of patients were female. The median
      haemoglobin concentration was 11.3 g/dL (interquartile range (IQR), 9.8-12.4) in
      females and 12.5 g/dL (IQR, 10.6-14.2) in males. Anaemia was present in the
      majority of children <10 years, women after puberty, and older adults. Children
      <5 years had the highest prevalence of anaemia, especially children aged 1-2
      years. The high proportion of microcytic anaemia and the fact that gender
      differences were only seen after the menarche period in women suggest that iron
      deficiency was the main cause of anaemia. However, the prevalence of normocytic
      anaemia increased with age. The results of this study can be used by public
      health programmes to design target interventions aimed at reducing the huge
      burden of anaemia in India. Further studies are needed to clarify the aetiology
      of anaemia among older adults. 

PMID- 25614832
TI  - Transvaginal appendectomy: a systematic review.
AB  - Background. Natural orifice transluminal endoscopic surgery (NOTES) is a new
      approach that allows minimal invasive surgery through the mouth, anus, or vagina.
      Objective. To summarize the recent clinical appraisal, feasibility,
      complications, and limitations of transvaginal appendectomy for humans and
      outline the techniques. Data Sources. PubMed/MEDLINE, Cochrane, Google-Scholar,
      EBSCO, clinicaltrials.gov and congress abstracts, were searched. Study Selection.
      All related reports were included, irrespective of age, region, race, obesity,
      comorbidities or history of previous surgery. No restrictions were made in terms
      of language, country or journal. Main Outcome Measures. Patient selection
      criteria, surgical techniques, and results. Results. There were total 112
      transvaginal appendectomies. All the selected patients had uncomplicated
      appendicitis and there were no morbidly obese patients. There was no standard
      surgical technique for transvaginal appendectomy. Mean operating time was 53.3
      minutes (25-130 minutes). Conversion and complication rates were 3.6% and 8.2%,
      respectively. Mean length of hospital stay was 1.9 days. Limitations. There are a
      limited number of comparative studies and an absence of randomized studies.
      Conclusions. For now, nonmorbidly obese females with noncomplicated appendicitis
      can be a candidate for transvaginal appendectomy. It may decrease postoperative
      pain and enable the return to normal life and work off time. More comparative
      studies including subgroups are necessary. 

PMID- 25614833
TI  - Laparoscopic watson fundoplication is effective and durable in children with
      gastrooesophageal reflux.
AB  - Gastroesophageal reflux (GOR) affects 2-8% of children over 3 years of age and is
      associated with significant morbidity. The disorder is particularly critical in
      neurologically impaired children, who have a high risk of aspiration.
      Traditionally, the surgical antireflux procedure of choice has been Nissen's
      operation. However, this technique has a significant incidence of mechanical
      complications and has a reoperation rate of approximately 7%, leading to the
      development of alternative approaches. Watson's technique of partial anterior
      fundoplication has been shown to achieve long-lasting reflux control in adults
      with few mechanical complications, but there is limited data in the paediatric
      population. We present here short- and long-term outcomes of laparoscopic Watson
      fundoplication in a series of 76 children and infants, 34% of whom had a degree
      of neurological impairment including severe cerebral palsy and hypoxic brain
      injury. The overall complication rate was 27.6%, of which only 1 was classified
      as major. To date, we have not recorded any incidences of perforation and no
      revisions. In our experience, Watson's laparoscopic partial fundoplication can be
      performed with minimal complications and with durable results, not least in
      neurologically compromised children, making it a viable alternative to the Nissen
      procedure in paediatric surgery. 

PMID- 25614834
TI  - Surgical and bronchoscopic lung volume reduction in chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the most extensively studied and
      researched disease in pulmonology and a cause of significant morbidity,
      mortality, and financial burden on patient's family and country's economy. Its
      management continues to be a challenge to both the physician and the patient's
      family. So far, it is preventable and treatable but not curable. Emphysema, a
      phenotype of COPD, is the most debilitating condition associated with progressive
      exercise intolerance and severe dyspnea. Despite decades of research, medical
      treatments available so far have helped improve quality of life and slowed down
      the decline in respiratory function but did not significantly improve the
      survival benefits. Though surgical lung volume reduction (LVR) procedures have
      shown some promise in context to functional gains and survival but, only in a
      carefully selected group of patients, bronchoscopic LVR procedures are yet to
      explore their full potential and limitations. This paper retrospectively studied
      the developments so far, medical and surgical, with special emphasis on the
      bronchoscopic procedures of lung volume reduction, and tried to comparatively
      analyze the risks and benefits of each one of them through various trials and
      studies done to date. 

PMID- 25614835
TI  - Temporal Synchrony Detection and Associations with Language in Young Children
      with ASD.
AB  - Temporally synchronous audio-visual stimuli serve to recruit attention and
      enhance learning, including language learning in infants. Although few studies
      have examined this effect on children with autism, it appears that the ability to
      detect temporal synchrony between auditory and visual stimuli may be impaired,
      particularly given social-linguistic stimuli delivered via oral movement and
      spoken language pairings. However, children with autism can detect audio-visual
      synchrony given nonsocial stimuli (objects dropping and their corresponding
      sounds). We tested whether preschool children with autism could detect audio
      visual synchrony given video recordings of linguistic stimuli paired with
      movement of related toys in the absence of faces. As a group, children with
      autism demonstrated the ability to detect audio-visual synchrony. Further, the
      amount of time they attended to the synchronous condition was positively
      correlated with receptive language. Findings suggest that object manipulations
      may enhance multisensory processing in linguistic contexts. Moreover,
      associations between synchrony detection and language development suggest that
      better processing of multisensory stimuli may guide and direct attention to
      communicative events thus enhancing linguistic development. 

PMID- 25614836
TI  - The combined effects of tai chi, resistance training, and diet on physical
      function and body composition in obese older women.
AB  - Obesity is a major health problem in the USA, especially in minority populations
      over the age of 60 years, and the aging process can cause adverse effects on
      physical function. Previous research has shown that Tai Chi, resistance training
      (RT), and diet result in overall health improvements. However, the combination of
      these specific interventions has yet to be translated to obese older women in an
      urban setting. The purpose of this study was to examine a combined intervention
      on the primary outcomes of physical function and body composition. Using a
      nonrandomized design, 26 obese women (65.2 +/- 8.1 years) completed a 12-week
      intervention; participants were assigned to an intervention (EXD) group or a
      control (CON) group. The EXD group (n = 17) participated in Tai Chi, RT, and a
      dietary session. The CON group (n = 9) was asked to continue their normal
      lifestyle. Timed up and go (TUG) time was reduced by 0.64 +/- 2.1 seconds (P =
      0.04) in the EXD group while the CON group saw a borderline significant increase
      of 0.71 sec (P = 0.051). The combined intervention helped improve performance on
      TUG time, but there were no significant increases in other body composition or
      function measures. 

PMID- 25614837
TI  - O Serogroup-Specific Touchdown-Multiplex Polymerase Chain Reaction for Detection
      and Identification of Vibrio cholerae O1, O139, and Non-O1/Non-O139.
AB  - A novel, sensitive locus-specific touchdown-multiplex polymerase chain reaction
      (TMPCR), which is based on two-stage amplification pertaining to multiplex PCR
      and conditional touchdown strategy, was used in detecting and differentiating
      Vibrio cholerae serogroups. A panel of molecular marker-based TMPCR method
      generates reproducible profiles of V. cholerae-specific (588 bp) amplicons
      derived from ompW gene encoding the outer membrane protein and serogroup-specific
      amplicons, 364 bp for the O1 and 256 bp for the O139, authentically copied from
      rfb genes responsible for the lipopolysaccharide biosynthesis. The TMPCR
      amplification efficiency yields either equally or unequally detectable duplex DNA
      bands of the O1 (588 and 364 bp) and O139 (588 and 256 bp) or a DNA fragment of
      non-O1/non-O139 (588 bp) while providing no false positive identifications using
      the genomic DNA templates of the other vibrios and Enterobacteriaceae. The
      reciprocal analysis of two-template combinations demonstrated that, using V.
      cholerae O1, O139, or equally mixed O1 and O139, the TMPCR had a detection limit
      of as low as 100 pg of the O1, O139, or non-O1/non-O139 in reactions containing
      unequally or equally mixed gDNAs. In addition, the O serogroup-specific TMPCR
      method had 100% agreement with the serotyping method when examined for the
      serotyped V. cholerae reference strains and those recovered from clinical
      samples. The potential benefit of using this TMPCR tool would augment the
      serotyping method used in epidemiological surveillance and monitoring of V.
      cholerae serogroups, O1, O139, and non-O1/non-O139 present in clinical and
      environmental samples. 

PMID- 25614839
TI  - Retrograde gastrojejunostomy tube migration.
AB  - Percutaneous enteral feeding tubes are placed about 250,000 times each year in
      the United States. Although they are relatively safe, their placement may be
      complicated by perforation, infection, bleeding, vomiting, dislodgment, and
      obstruction. There have been numerous reports of antegrade migration of
      gastrojejunostomy (G-J) tubes. We report a case of G-J tube regurgitation
      following protracted vomiting and discuss the management of this very rare
      entity. 

PMID- 25614840
TI  - Emergency open incarcerated hernia repair with a biological mesh in a patient
      with colorectal liver metastasis receiving chemotherapy and bevacizumab
      uncomplicated wound healing.
AB  - Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial
      growth factor (VEGF), often used in combinational chemotherapy regimens for the
      treatment of patients with colorectal liver metastases. However adverse events
      have been attributed to the use of bevacizumab including gastrointestinal
      perforations, thrombotic events, hypertension, bleeding, and wound healing
      complications. 53-year-old male, with a history of colorectal cancer with liver
      metastasis, receiving a combination of cytotoxic chemotherapy (FOLFIRI,
      irinotecan with fluorouracil and folinic acid) with bevacizumab presented as an
      emergency with an incarcerated incisional hernia. The last administration of
      chemotherapy and bevacizumab had taken place 2 weeks prior to this presentation.
      As the risk of strangulation of the bowel was increased, a decision was made to
      take the patient to theatre, although the hazard with respect to wound healing,
      haemorrhage, and infection risk was high due to the recent administration of
      chemotherapy with bevacizumab. The patient underwent an open repair of the
      incarcerated recurrent incisional hernia with placement of a biological mesh, and
      the postoperative recovery was uncomplicated with no wound healing or bleeding
      problems. 

PMID- 25614841
TI  - Acute renal infarction presenting with acute abdominal pain secondary to newly
      discovered atrial fibrillation: a case report and literature review.
AB  - We report an 85-year-old female with known history of recurrent diverticulitis
      presented with abdominal pain. It was believed that the patient again needed to
      be treated for another diverticulitis and was started on the routine treatment.
      The initial CT scan of abdomen showed renal infarcts bilaterally that were
      confirmed by a CT with and without intravenous contrast secondary to unknown
      cause. An ECG found accidentally that the patient was in atrial fibrillation,
      which was the attributed factor to the renal infarctions. Subsequently, the
      patient was started on the appropriate anticoagulation and discharged. 

PMID- 25614842
TI  - Severe Gastroparesis following Radiofrequency Catheter Ablation for Atrial
      Fibrillation: Suggestion for Diagnosis, Treatment, and Device for Gastroparesis
      after RFCA.
AB  - Gastroparesis following radiofrequency catheter ablation (RFCA) is a very rare
      complication, as only two cases have been reported in the English literature. A
      42-year-old man underwent RFCA due to recurrent drug-resistant symptomatic atrial
      fibrillation. The patient complained of indigestion and early satiety 2 days
      after the procedure. Contrast-enhanced computed tomography and an upper
      gastrointestinal series of the abdomen showed a large amount of material
      remaining in the stomach area. All food material was removed by endoscopy, and
      the patient received medical treatment. We suggest a flow chart for diagnosis and
      treatment of AFGS based on the present case and previous cases. Endoscopic
      medical patent was designed on the basis of this case. 

PMID- 25614838
TI  - Chlamydia trachomatis and Genital Mycoplasmas: Pathogens with an Impact on Human
      Reproductive Health.
AB  - The most prevalent, curable sexually important diseases are those caused by
      Chlamydia trachomatis (C. trachomatis) and genital mycoplasmas. An important
      characteristic of these infections is their ability to cause long-term sequels in
      upper genital tract, thus potentially affecting the reproductive health in both
      sexes. Pelvic inflammatory disease (PID), tubal factor infertility (TFI), and
      ectopic pregnancy (EP) are well documented complications of C. trachomatis
      infection in women. The role of genital mycoplasmas in development of PID, TFI,
      and EP requires further evaluation, but growing evidence supports a significant
      role for these in the pathogenesis of chorioamnionitis, premature membrane
      rupture, and preterm labor in pregnant woman. Both C. trachomatis and genital
      mycoplasmas can affect the quality of sperm and possibly influence the fertility
      of men. For the purpose of this paper, basic, epidemiologic, clinical,
      therapeutic, and public health issue of these infections were reviewed and
      discussed, focusing on their impact on human reproductive health. 

PMID- 25614843
TI  - Varicella Zoster Virus Meningitis in a Young Immunocompetent Adult without Rash:
      A Misleading Clinical Presentation.
AB  - Meningitis caused by varicella zoster virus (VZV) is rare in healthy population.
      Predominantly immunocompromised patients are affected by reactivation of this
      virus with primary clinical features of rash and neurological symptoms. Here we
      report a young otherwise healthy man diagnosed with a VZV meningitis without
      rash. He complained of acute headache, nausea, and vomiting. The clinical
      examination did not show any neurological deficits or rash. Cerebrospinal fluid
      (CSF) analysis revealed a high leukocyte cell count of 1720 cells/uL and an
      elevated total protein of 1460 mg/L misleadingly indicating a bacterial
      infection. Further CSF analyses, including polymerase chain reaction (PCR) and
      detection of intrathecal synthesis of antibodies, showed a VZV infection.
      Clinical and CSF follow-up examinations proved the successful antiviral
      treatment. In conclusion, even young immunocompetent patients without rash might
      present with VZV meningitis. CSF examination is a key procedure in the diagnosis
      of CNS infections but in rare cases the standard values cell count and total
      protein might misleadingly indicate a bacterial infection. Thus, virological
      analyses should be considered even when a bacterial infection is suspected. 

PMID- 25614844
TI  - Tubal pregnancy associated with endometrial carcinoma after in vitro
      fertilization attempts.
AB  - Endometrial carcinoma is rarely seen during reproductive ages and commonly
      related to infertility, polycystic ovarian syndrome (PCOS), and obesity.
      Pregnancy associated endometrial carcinoma is even rarer and this is the second
      case reported in the literature concerning tubal pregnancy associated endometrial
      carcinoma. We present a case of a 36-year-old woman with a history of PCOS,
      infertility, and several attempts of ovulation induction and in vitro
      fertilization, who was diagnosed with tubal pregnancy and a well differentiated
      endometrial carcinoma. We also review the literature about pregnancy associated
      endometrial carcinoma in the first trimester. 

PMID- 25614845
TI  - A case of gingival candidiasis with bone destruction on gastric cancer patient
      receiving cytotoxic chemotherapy.
AB  - We herein report a case of gingival candidiasis in an advanced gastric cancer
      patient while receiving palliative cytotoxic chemotherapy. A 46-year-old male
      patient admitted to our hospital for known advanced gastric cancer with newly
      developed multiple liver metastases. While receiving 2nd line cytotoxic
      chemotherapy with 5FU, leucovorin, and paclitxel, he complained of gingival
      swelling accompanied by pain and whitish plaque. Due to lack of response to the
      conservative oral care, incisional biopsy of gingiva was done and the pathology
      confirmed gingival candidiasis. Although the lesion healed apparently after two
      week antifungal therapy, pain as well as bony destruction remains. By presenting
      this case report, we intend to emphasize the immunocompromising effect of cancer
      while being on systemic chemotherapy. 

PMID- 25614846
TI  - Granulocytic Sarcoma of the Uterus: A Rare Presentation of Extramedullary Relapse
      of AML and Importance of MRI.
AB  - Granulocytic sarcoma (GS) is a solid tumor that is the extramedullary
      presentation of acute myelogenous leukemia, other myeloproliferative disorders,
      or myelodysplastic syndromes. Less commonly, it also may arise as an isolated
      mass. In this report, we describe a 23-year-old female patient, with a GS in the
      uterus and we stress the value of diffusion weighted imaging for the evaluation
      of uterine neoplasms. To our knowledge, our case is the first in the literature
      to report diffusion weighted imaging (DWI) findings of GS. 

PMID- 25614847
TI  - Perforated jejunal diverticula secondary to a large faecolith: a rare cause of
      the acute abdomen.
AB  - Jejunal diverticula are uncommon and usually asymptomatic. Very rarely, they can
      lead to acute complications such as bleeding, obstruction, and perforation. This
      report describes our experience of a case of jejunal diverticula perforation
      secondary to a large faecolith, with particular focus on the aetiology and
      management of this rare condition. 

PMID- 25614848
TI  - Persistent high level of urinary tumor marker carbohydrate antigen 19-9 in
      prenatally diagnosed dysplastic kidney.
AB  - Tumor marker carbohydrate antigen 19-9 (CA 19-9) level has gained clinical
      significance in gastrointestinal malignancies and in various solid and cystic
      diseases. Dysplastic kidney is a congenital abnormality resulting from atresia of
      the ureteral bud during the embryogenesis which can be unilateral or bilateral.
      We report unilateral dysplastic kidney with extremely large cyst diagnosed by
      routine ultrasonography in the 32nd week of gestational age with high levels of
      CA 19-9 in cystic and amniotic fluid, as well as persistent high urinary levels
      of this tumor marker during the 1-year follow-up. Persistent high urinary CA 19-9
      level even after cyst aspiration may be attributable to remained function of
      dysplastic kidney due to remained epithelial lining. 

PMID- 25614849
TI  - Comparison of the Psychological Symptoms and Disease-Specific Quality of Life
      between Early- and Typical-Onset Parkinson's Disease Patients.
AB  - The impact of Parkinson's disease (PD) on psychological status and quality of
      life (QoL) may vary depending on age of disease onset. The aim of this study was
      to compare psychological symptoms and disease-specific QoL between early onset
      versus the rest of the PD patients. A total number of 140 PD patients with the
      mean current age of 61.3 (SD = 10.4) yr were recruited in this study. PD patients
      with the onset age of <=50 yr were defined as "early-onset" (EOPD) group (n =
      45), while the ones with >50 yr at the time of diagnosis were categorized as the
      "typical-onset" (TOPD) patients (n = 95). Different questionnaires and scales
      were used for between-group comparisons including PDQ39, HADS (hospital anxiety
      and depression scale), FSS (fatigue severity scale), MNA (mininutritional
      assessment), and the UPDRS. Depression score was significantly higher in EOPD
      group (6.3 (SD = 4.5) versus 4.5 (SD = 4.2), P = 0.02). Among different domains
      of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD =
      21.6) versus 24.4 (SD = 22.7), P = 0.05). Our findings showed more severe
      depression and more impaired emotional domain of QoL in early-onset PD patients.
      Depression and anxiety play an important role to worsen QoL among both EOPD and
      TOPD patients, while no interaction was observed in the efficacy of these two
      psychiatric symptoms and the onset age of PD patients. 

PMID- 25614850
TI  - Chitosan hydrogels for chondroitin sulphate controlled release: an analytical
      characterization.
AB  - This paper provides an analytical characterization of chitosan scaffolds obtained
      by freeze-gelation toward the uptake and the controlled release of chondroitin
      sulphate (CS), as cartilage repair agent, under different pH conditions. Scanning
      electron microscopy (SEM), attenuated total reflectance-Fourier transform
      infrared spectroscopy (ATR-FTIR), and liquid chromatography-UV spectrophotometry
      (LC-UV) techniques were exploited to obtain qualitative and quantitative
      descriptions of polymer and drug behaviour in the biomaterial. As for morphology,
      SEM analysis allowed the evaluation of scaffold porosity in terms of pore size
      and distribution both at the surface (Feret diameter 58 +/- 19 MUm) and on the
      cross section (Feret diameter 106 +/- 51 MUm). LC and ATR-FTIR evidenced a pH
      dependent CS loading and release behaviour, strongly highlighting the role of
      electrostatic forces on chitosan/chondroitin sulphate interactions. 

PMID- 25614851
TI  - Sociosexuality, human immunodeficiency virus (HIV) susceptibility, and sexual
      behavior among African American women.
AB  - Psychosocial correlation of risky sexual behavior is important for the design and
      implementation of human immunodeficiency virus (HIV)-related prevention and
      intervention studies. Sociosexuality (individual differences in endorsement of
      casual sexual behavior) and perceived susceptibility to HIV were examined for
      their relationship to each other, and in predicting risky sexual behavior among
      adult, heterosexual African American women using web-based and in-person surveys.
      This study included 275 geographically diverse women (mean age = 33.60 years),
      with 81% reported having at least a college degree, and over 50% reported incomes
      over $45,000. Results indicate that sociosexuality was significantly associated
      with perceived susceptibility, and both higher levels of sociosexuality and
      perceived susceptibility were significantly related to engagement in riskier
      sexual behavior. Age at first voluntary intercourse emerged as an important
      covariate in predicting risky sexual behavior among the participants. The need to
      include psychosocial variables associated with risky sexual behavior in sexually
      transmitted infection (STI) and HIV-related health promotion and intervention
      studies was discussed.

PMID- 25614852
TI  - Gender roles, sociosexuality, and sexual behavior among US Black women.
AB  - This study examined the relationship between gender roles and sociosexuality (an
      individual difference variable describing attitudes about sexual permissiveness
      and promiscuity), and their predictive pattern of HIV-related sexual risk
      behaviors. A geographically diverse sample of 275 adult, heterosexual Black women
      (mean age = 33.60 years), participated in a self-administered survey. Significant
      relationships were found between feminine traits and sociosexuality, and between
      sociosexuality and four of the five risky sexual behavior variables. Neither
      masculine nor feminine gender roles were related to any risky sexual behavior
      variables. Sociosexuality emerged as an important correlate that requires further
      exploration of its relationship to the attitudes and behaviors of Black women,
      and its potential relationship to HIV risk-related sexual behavior. The need for
      more attention to psychosocial variables, and consideration of context, cultural
      norms, and values is discussed as an important undertaking in order to garner an
      accurate picture of sexual risk behavior.

PMID- 25614854
TI  - Focal treatment for genetic disorders (a fairy tale or a true story?).

PMID- 25614853
TI  - An overview on the successes, challenges and future perspective of a national
      school-based surveillance program: the CASPIAN study.
AB  - The Childhood and Adolescence Surveillance and PreventIon of Adult Non
      communicable disease (CASPIAN) study is implemented in the Islamic Republic of
      Iran from 2003. The aim of this national school- based surveillance program was
      to provide accurate data of regular surveys of this program to be reviewing
      methodology, protocols, data collection and questionnaires of these surveys.
      Information was obtained from articles and books were published from CASPIAN
      studies. The CASPIAN studies were repeated every two years, with blood sampling
      for biochemical factors every four years. Methods and questionnaires of all
      surveys were similar at their core level and some optional factors added in
      different surveys. The results of CASPIAN studies represent the public health of
      Iranian children and adolescents that are useful for policy makers and based on
      them, intervention programs can set in national and sub-national level. 

PMID- 25614855
TI  - The Prevalence of Risk Factors of Coronary Artery Disease in the Patients who
      Underwent Coronary Artery Bypass Graft, Shiraz, Iran: Suggesting a Model.
AB  - BACKGROUND: Cardiovascular diseases are the main cause of 40% of deaths in Iran
      annually. Many patients undergoing coronary artery bypass graft surgery have
      previous cardiovascular risk factors which could be prevented. OBJECTIVES: The
      present study aimed to assess the prevalence of cardiovascular risk factors in
      the patients undergoing coronary artery bypass graft surgery. MATERIALS AND
      METHODS: In this cross-sectional (descriptive - analytical) study, a data
      collecting form was used. A total of 246 patients were selected from six
      hospitals of Shiraz using random stratification. Descriptive statistics were
      presented through figures and tables and t-test was used to analyze the
      continuous variables. All the statistical analyses were performed using the SPSS
      statistical software (version 15.0). Besides, P < 0.05 was considered as
      statistically significant. RESULTS: Among the study patients, only 11.67% had no
      risk factors and 88.33% had one or more risk factors. The most common risk
      factors observed in the patients were hypertension, obesity and overweight,
      hyperlipidemia, and diabetes mellitus. The results showed a significant
      difference between males and females regarding the prevalence of hypertension (P
      = 0.001), diabetes (P = 0.028), hypercholesterolemia (P = 0.020), and cigarette
      smoking (P = 0.001). In addition, the patients' mean levels of cholesterol, LDL,
      triglyceride, and fasting blood sugar were higher than the acceptable level,
      while that of HDL was lower than the accepted level. CONCLUSIONS: These patients
      are recommended to be trained regarding lifestyle changes. Also, prevention
      strategies can play an important role in reducing patient morbidity and
      mortality.

PMID- 25614856
TI  - Assessment of the Relationship between Galectin-3 and Ejection Fraction and
      Functional Capacity in the Patients with Compensated Systolic Heart Failure.
AB  - BACKGROUND: Galectin-3 is a soluble beta-galactoside-binding lectin released by
      activated cardiac macrophages. Galectin-3 has been proposed for diagnosis and
      prognosis of HF patients. OBJECTIVES: The present study aimed to investigate the
      relationship between galectin-3 as a biomarker and ejection fraction and
      functional capacity in the patients with compensated systolic heart failure.
      PATIENTS AND METHODS: In this study, serum levels of Galectin-3 were measured in
      76 patients with compensated heart failure with New York Heart Association class
      I-IV and left ventricular ejection fraction < 45%. Galectin-3 was measured by an
      ELISA kit. Besides, echocardiography was used to evaluate left ventricular
      ejection fraction. Additionally, functional capacity was determined based on the
      patients' ability to perform a set of activities. After all, the data were
      analyzed used t-test, Kruskal-Wallis, one-way ANOVA, and chi-square test. P <
      0.05 was considered as statistically significant. RESULTS: The patients' age
      ranged from 45 to 75 years, with the mean age of 63.85 +/- 9 years. In addition
      57.9% of the patients were male. The results revealed no significant correlation
      between Galectin-3 and age, body mass index, and estimated glomerular filtration
      rate. Also, no significant correlation was observed between Galectin-3 levels and
      left ventricular ejection fraction (P = 0.166) and functional capacity (P =
      0.420). Yet, a significant difference was found between males and females
      regarding the mean of Galectin-3 (P = 0.039). CONCLUSIONS: The study results
      suggested that Galectin-3 could not be used as a marker of disease progression in
      the patients under treatment, which could probably be the result of medication
      use in these patients.

PMID- 25614857
TI  - The effect of elective percutaneous coronary intervention of the right coronary
      artery on right ventricular function.
AB  - BACKGROUND: Right Ventricular (RV) dysfunction has been introduced as a predictor
      of mortality in acute myocardial infarction. OBJECTIVES: This study aimed to
      investigate the effect of right coronary revascularization on systolic and
      diastolic RV dysfunction. PATIENTS AND METHODS: This study was conducted on
      unstable angina patients who were candidate for elective Percutaneous
      Revascularization Intervention (PCI) on the right coronary artery. The
      participants were initially evaluated by transthoracic echocardiography and
      tissue Doppler imaging prior to PCI and the RV function parameters were assessed.
      Echocardiography was repeated two months after PCI and the results were compared
      with baseline. Paired t-test was used to compare the pre- and post-procedural
      measurements. Besides, Pearson's correlation was used to find out the linear
      association between the RV function parameters and Left Ventricular Ejection
      Fraction (LVEF). P value < 0.05 was considered as statistically significant.
      RESULTS: This study was conducted on 30 patients (mean age = 60.00 +/- 8.44
      years; 24 [80%] males). In the pre-procedural echocardiography, 15 patients (50%)
      had normal RV function, 14 patients (46.7%) had grade-1 RV dysfunction, and only
      1 patient (3.3%) had grade-2 RV dysfunction. Following PCI, however, all the
      patients had normal systolic and diastolic RV functions. Comparison of
      echocardiographic RV function parameters showed an improvement in both systolic
      and diastolic functional parameters of the RV. Nonetheless, no significant
      correlation was observed between these parameters and Left Ventricular (LV)
      function. CONCLUSIONS: A significant improvement was found in RV function, but
      not LV function, after right coronary PCI. Revascularization of the right
      coronary artery may be beneficial for the patients who suffer from RV failure due
      to ischemia.

PMID- 25614858
TI  - Incidence and outcome of documented fungal endocarditis.
AB  - BACKGROUND: Fungal endocarditis, the most severe form of infective endocarditis,
      is characterized by excessive mortality and morbidity. OBJECTIVES: The present
      study aimed to analyze the characteristics of fungal endocarditis to improve the
      management of these patients. MATERIALS AND METHODS: In this cross-sectional
      study, vegetations on the mitral or tricuspid valves and embolic material
      surgically removed from the patients with suspected infective endocarditis
      between December 2009 and November 2011 were examined for fungal infection by
      direct smear and culture, and the susceptibility patterns of the isolated species
      were determined. Then, blood samples were cultured on BACTEC media and real-time
      PCR was done with blood and tissue samples. RESULTS: Of the 31 patients with
      suspected infective endocarditis who did not respond to antibacterial therapy, 11
      had confirmed fungal endocarditis. The most frequent predisposing risk factors
      were previous surgery and drug abuse. The organisms isolated were Aspergillus
      spp. and Candida albicans. Resistance to amphotericin B and itraconazole was
      observed in Aspergillus species, and to fluconazole in Candida albicans. Positive
      PCR results were obtained in blood and tissue samples. CONCLUSIONS: Fungal
      endocarditis should be considered in the patients not responsive to
      antimicrobials. Moreover, management of these patients can be improved with
      molecular diagnostic methods and by determining the susceptibility patterns of
      the etiologic agents.

PMID- 25614859
TI  - Metabolic syndrome and inflammatory biomarkers in adults: a population-based
      survey in Western region of iran.
AB  - BACKGROUND: There is evidence that inflammation may be involved in pathogenesis
      of MetS. Inflammatory biomarkers are moving to the forefront as the potent
      predictors of MetS. OBJECTIVES: The present study aimed to evaluate the
      association between MetS and some inflammatory biomarkers. PATIENTS AND METHODS:
      This community-based cross-sectional study was conducted on 800 subjects aged
      above 35 years selected through random sampling in Borujerd (west of Iran) from
      2011 to 2013. MetS was defined based on ATP III criteria and the subjects were
      divided into two groups (MetS and non-MetS groups). Waist circumference and Body
      Mass Index (BMI) were calculated. In addition, blood samples were taken and C
      Reactive Protein (CRP), lipid profile, Fasting Blood Sugar (FBS), and Bleeding
      Time (BT) were measured. Then, the correlations between MetS and the above
      mentioned variables were estimated. After all, the data were entered into the
      SPSS statistical software (v. 17) and analyzed using T-test, chi-square, median
      test, and spearman's rank correlation. RESULTS: In this study, 344 subjects (43%)
      met the ATP III criteria. The results showed a significant difference between
      MetS and non-MetS groups regarding BMI, white blood cell, total cholesterol, LDL,
      platelet, and high-sensitivity CPR (hs-CRP) (P < 0.0001, P = 0.040, P < 0.0001, P
      < 0.0001, and P = 0.045, respectively). Besides, waist circumference,
      Triglyceride (TG), FBS, and systolic and diastolic blood pressure were
      significantly higher, while HDL was significantly lower in the MetS group (P <
      0.0001). CONCLUSIONS: The incidence rate of MetS in our survey was higher
      compared to the previous reports. In addition, this incidence rate was higher in
      females in comparison to males. The results also showed a significant correlation
      between inflammatory biomarkers and MetS and that the higher levels of hs-CRP
      were associated with higher rate of MetS.

PMID- 25614860
TI  - QT Dispersion after Thrombolytic Therapy.
AB  - BACKGROUND: QT dispersion (QTd) is equal to longer QTc minus shorter QTc measured
      by 12-lead electrocardiogram (ECG). QTd reflects inhomogeneity in repolarization
      of ventricular myocardium and because of easy and fast measurement of QTd, it can
      be used to predict high-risk patients for dysrhythmia after Acute Myocardial
      Infarction (AMI). OBJECTIVES: This study aimed to assess the effect of
      thrombolytic therapy on QTd before and 1 hour and 4 days after beginning of
      thrombolytic therapy. PATIENTS AND METHODS: The patients with chest pain and ST
      Elevated Myocardial Infarction (STEMI) that underwent thrombolytic therapy were
      enrolled into this study. Streptokinase was the thrombolytic agent in all the
      patients. Standard 12-lead (ECG) was evaluated before beginning of thrombolytic
      therapy (QTd 1) and 1 hour (QTd2) and 4 days (QTd3) after thrombolytic therapy.
      First, ECG was magnified * 10 for exact calculation of QT and QTd. After all, the
      variables were compared using one-way analysis of variance (ANOVA). Besides, P <=
      0.05 was considered as statistically significant. RESULTS: This study was
      conducted on 160 patients. The results revealed no significant differences among
      QTd 1, QTd 2, and QTd 3 (P > 0.05). At inferior AMI, however, a significant
      difference was observed among QTd1, QTd2, and QTd3 (P = 0.031). CONCLUSIONS:
      Thrombolytic therapy had no significant effects on QTd. Thus, thrombolytic
      therapy does not increase the risk of arrhythmia.

PMID- 25614861
TI  - Dealing with coronary artery disease in early encountering: a qualitative study.
AB  - BACKGROUND: The prevalence of cardiovascular diseases is rising in industrial and
      developing countries. Coronary Artery Disease (CAD) is the most common
      cardiovascular disease. Thus, understanding the signs and risk factors of CAD
      from the patients' perspective and their ways of dealing with this disease is of
      vital importance. OBJECTIVES: This qualitative study aimed to explore the Iranian
      patients' viewpoints about CAD and how they dealt with it in their first
      encounter. PATIENTS AND METHODS: This study was a qualitative content analysis
      conducted on 18 patients with CAD. The data were collected through semi
      structured interviews. Initially, purposeful sampling was performed followed by
      maximum variety. Sampling continued until data saturation. Then, all the
      interviews were recorded and transcribed verbatim. After all, the data were
      analyzed by constant comparative analysis using MAXQUDA2010 software. RESULTS:
      The themes manifested in this study included "invasion of disease" with subthemes
      of "warning signs" and "risk factors" and "confrontation strategies" with
      subthemes of "seeking for information", "follow-up", and "control measures".
      CONCLUSIONS: The results of this study described the patients' perceptions of CAD
      and how they dealt with this disorder in early encountering. Based on the
      results, physicians and nurses should focus on empowerment of patients by
      facilitating this process as well as by educating them with regards to dealing
      with CAD.

PMID- 25614862
TI  - Depression Mediates the Effect of Sexual Function on Quality of Life among Men
      but Not Women with Coronary Artery Disease.
AB  - BACKGROUND: Poor sexual function is associated with impaired Health-Related
      Quality of Life (HRQoL), and patients with Coronary Artery Disease (CAD) are not
      exceptions. It is not known, however, if symptoms of depression mediate the
      effect of sexual function on HRQoL among men and women with CAD. OBJECTIVES: This
      study aimed to determine the mediating effect of depressive symptoms on the
      association between sexual function and HRQoL among men and women with CAD.
      PATIENTS AND METHODS: This cross-sectional study was conducted on 401 men and 156
      women with CAD. Sexual function, measured by the Relation and Sexuality Scale
      (RSS), was the independent variable. In addition, physical and mental HRQoL
      measured using physical and mental health summary scores of Short Form 36 (SF-36)
      were dependent variables. Besides, the severity of depressive symptoms measured
      by the Hospital Anxiety and Depression Scale (HADS) was conceptualized as the
      mediator. Age, income, education, and medical comorbidities (Ifudu index) were
      control variables, and gender was the moderator. Multi-group path analysis was
      conducted using AMOS20.0 for data analysis. RESULTS: When the effects of age,
      education, income, and comorbidities were controlled, sexual function was
      correlated with poor mental HRQoL in both genders. However, the association
      between sexual function and poor physical HRQoL could be found only among men but
      not women. Evidence also supported partial mediation of depressive symptoms on
      the effect of sexual function on mental HRQoL of both men and women. Nonetheless,
      the results suggested partial mediation of depressive symptoms on the effect of
      sexual function on physical HRQoL only among men but not women. CONCLUSIONS:
      Symptoms of depression may not have a similar role in explaining the effect of
      sexual function on physical HRQoL of men and women with CAD. Our findings suggest
      that only among men, depressive symptoms might be the mechanism by which sexual
      function affects the CAD patients' physical HRQoL.

PMID- 25614863
TI  - Improvement of dilated cardiomyopathy with methylprednisolone in a patient with
      multiple fibrosclerosis.
AB  - Multifocal fibrosclerosis is a rare syndrome of unknown cause that is
      characterized by fibrosis involving multiple organ systems. Definitive diagnosis
      can only be made based on biopsy findings. In this case, the biopsy specimen of
      the patient demonstrates pulmonary hyalinated granuloma or sclerosing
      mediastinitis. There are few reports of multiple fibrosclerosis with heart
      failure. Here, we reported a case of retroperitoneal fibrosis with massive
      mediastinal involvement extending to pleura and pericardium causing pleuro-
      pericardial effusion with dilated cardiomyopathy. Systolic dysfunction was
      improved and pericardial effusion disappeared with methylprednisolone treatment. 

PMID- 25614864
TI  - Mitral-aortic intervalvular fibrosa involvement by takayasu' arteritis.
AB  - Takayasu's arteritis is an inflammatory disease with a variety of manifestations,
      such as cardiac involvement. We describe a 52-year-old woman with clinical and
      echocardiographic manifestations mimicking infectious endocarditis, such as
      periaortic and mital-aortic intervalvular fibrosa abscess with extension to the
      anterior mitral leaflet. However, no infective tissue was discovered
      intraoperatively. Pathological evaluation demonstrated Takayasu's arteritis. To
      the best of our knowledge, Takayasu's arteritis can involve mitral-aortic
      intervalvular fibrosa and imitate infectious endocarditis. 

PMID- 25614865
TI  - Tobacco smoking: the evidence from prevention and cessation.

PMID- 25614866
TI  - Driving personalized medicine forward: the who, what, when, and how of educating
      the health-care workforce.

PMID- 25614867
TI  - Medical genetics in paraguay.

PMID- 25614868
TI  - Terminal osseous dysplasia with pigmentary defects (TODPD) due to a recurrent
      filamin A (FLNA) mutation.
AB  - Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked
      dominant syndrome with distal limb anomalies, pigmentary skin defects, digital
      fibromas, and generalized bone involvement due to a recurrent mutation in the
      filamin A (FLNA) gene. We here report the mutation c.5217G>A in FLNA in three
      families with TODPD and we found possible germline and somatic mosaicism in two
      out of the three families. The occurrence of somatic and germline mosaicism for
      TODPD indicates that caution should be taken in counseling recurrence risks for
      these conditions upon presentation of an isolated case. 

PMID- 25614869
TI  - Exome analysis identifies Brody myopathy in a family diagnosed with malignant
      hyperthermia susceptibility.
AB  - Whole exome sequencing (WES) was used to determine the primary cause of muscle
      disorder in a family diagnosed with a mild, undetermined myopathy and malignant
      hyperthermia (MH) susceptibility (MHS). WES revealed the compound heterozygous
      mutations, p.Ile235Asn and p.Glu982Lys, in ATP2A1, encoding the
      sarco(endo)plasmic reticulum Ca(2+) ATPase type 1 (SERCA1), a calcium pump,
      expressed in fast-twitch muscles. Recessive mutations in ATP2A1 are known to
      cause Brody myopathy, a rare muscle disorder characterized by exercise-induced
      impairment of muscle relaxation and stiffness. Analyses of affected muscles
      showed the absence of SERCA1, but SERCA2 upregulation in slow and fast myofibers,
      suggesting a compensatory mechanism that partially restores the diminished Ca(2+)
      transport in Brody myopathy. This compensatory adaptation to the lack of SERCA1
      Ca(2+) pumping activity within the muscle explains, in part, the mild course of
      disease in our patient. Diagnosis of MHS in this family was secondary to a loss
      of SERCA1 due to disease-associated mutations. Although there are obvious
      differences in clinical expression and molecular mechanisms between MH and Brody
      myopathy, a feature common to both conditions is elevated myoplasmic Ca(2+)
      content. Prolonged intracellular Ca(2+) elevation is likely to have led to MHS
      diagnosis in vitro and postoperative MH-like symptoms in Brody patient. 

PMID- 25614870
TI  - Functional and structural impact of the most prevalent missense mutations in
      classic galactosemia.
AB  - Galactose-1-phosphate uridylyltransferase (GALT) is a key enzyme in galactose
      metabolism, particularly important in the neonatal period due to ingestion of
      galactose-containing milk. GALT deficiency results in the genetic disorder
      classic galactosemia, whose pathophysiology is still not fully elucidated.
      Whereas classic galactosemia has been hypothesized to result from GALT
      misfolding, a thorough functional-structural characterization of GALT most
      prevalent variants was still lacking, hampering the development of alternative
      therapeutic approaches. The aim of this study was to investigate the structural
      functional effects of nine GALT mutations, four of which account for the vast
      majority of the mutations identified in galactosemic patients. Several
      methodologies were employed to evaluate the mutations' impact on GALT function,
      on the protein secondary and tertiary structures, and on the aggregation
      propensity. The major structural effect concerns disturbed propensity for
      aggregation, particularly striking for the p.Q188R variant, resulting from the
      most frequent (~60%) allele at a worldwide scale. The absence of major effects at
      the secondary and tertiary structure levels suggests that the disturbed
      aggregation results from subtle perturbations causing a higher and/or longer
      exposure of hydrophobic residues in the variants as compared to WT GALT. The
      results herein described indicate a possible benefit from introducing
      proteostasis regulators and/or chemical/pharmacological chaperones to prevent the
      accumulation of protein aggregates, in new avenues of therapeutic research for
      classic galactosemia. 

PMID- 25614871
TI  - FGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia
      Registry.
AB  - Fibroblast growth factor receptor 3 (FGFR3) is the only gene known to cause
      achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types
      I and II (TD I and TD II). A second, as yet unidentified, gene also causes HCH.
      In this study, we used sequencing analysis to determine the frequency of FGFR3
      mutations for each phenotype in 324 cases from the International Skeletal
      Dysplasia Registry (ISDR). Our data suggest that there is a considerable overlap
      of genotype and phenotype between ACH and HCH. Thus, it is important to test for
      mutations found in either disorder when ACH or HCH is suspected. Only two of 29
      cases with HCH did not have an identified mutation in FGFR3, much less than
      previously reported. We recommend testing other mutations in FGFR3, instead of
      just the common HCH mutation, p.Asn540Lys. The mutation frequency for TD I and TD
      II in the largest series of cases to date are also reported. This study provides
      valuable information on FGFR3 mutation frequency of four skeletal dysplasias for
      clinical diagnostic laboratories and clinicians. 

PMID- 25614872
TI  - Ten new ATM alterations in Polish patients with ataxia-telangiectasia.
AB  - Inherited biallelic mutations of the ATM gene are responsible for the development
      of ataxia telangiectasia (AT). The objective of the present study was to conduct
      molecular analysis of the ATM gene in a cohort of 24 Polish patients with ataxia
      telangiectasia with aim being to provide an updated mutational spectrum in Polish
      AT patients. As a result of molecular analysis, the status of recurrent mutation
      was confirmed and ten new ATM variants were detected. Application of MLPA
      analysis allowed the detection of large genomic deletion. Previously, this type
      of mutation had never been seen in our population. Finally, in silico analysis
      was carried out for newly detected ATM alterations. In addition, functional
      analysis was performed to evaluate the effects of intronic variants:
      c.3402+30_3402+32delATC. 

PMID- 25614873
TI  - A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1
      deletion.
AB  - Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are
      associated with intellectual disability and various psychiatric disorders, in
      particular, autism and schizophrenia. We present three unrelated patients, two
      adults and one child, in whom we identified an intragenic 2p16.3 deletion within
      the NRXN1 gene using an oligonucleotide comparative genomic hybridization array.
      The three patients presented dual diagnosis that consisted of mild intellectual
      disability and autism and bipolar disorder. Also, they all shared a dysmorphic
      phenotype characterized by a long face, deep set eyes, and prominent premaxilla.
      Genetic analysis of family members showed two inherited deletions. A
      comprehensive neuropsychological examination of the 2p16.3 deletion carriers
      revealed the same phenotype, characterized by anxiety disorder, borderline
      intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive
      syndrome with poor working memory and reduced attention switching, mental
      flexibility, and verbal fluency was the same than those of the adult probands. We
      suggest that in addition to intellectual disability and psychiatric disease,
      NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic
      profile. The new cognitive phenotype found in the 2p16.3 deletion carriers
      suggests that 2p16.3 deletions might have a wide variable expressivity instead of
      incomplete penetrance. 

PMID- 25614874
TI  - The allelic spectrum of Charcot-Marie-Tooth disease in over 17,000 individuals
      with neuropathy.
AB  - We report the frequency, positive rate, and type of mutations in 14 genes (PMP22,
      GJB1, MPZ, MFN2, SH3TC2, GDAP1, NEFL, LITAF, GARS, HSPB1, FIG4, EGR2, PRX, and
      RAB7A) associated with Charcot-Marie-Tooth disease (CMT) in a cohort of 17,880
      individuals referred to a commercial genetic testing laboratory. Deidentified
      results from sequencing assays and multiplex ligation-dependent probe
      amplification (MLPA) were analyzed including 100,102 Sanger sequencing, 2338 next
      generation sequencing (NGS), and 21,990 MLPA assays. Genetic abnormalities were
      identified in 18.5% (n = 3312) of all individuals. Testing by Sanger and MLPA (n
      = 3216) showed that duplications (dup) (56.7%) or deletions (del) (21.9%) in the
      PMP22 gene accounted for the majority of positive findings followed by mutations
      in the GJB1 (6.7%), MPZ (5.3%), and MFN2 (4.3%) genes. GJB1 del and mutations in
      the remaining genes explained 5.3% of the abnormalities. Pathogenic mutations
      were distributed as follows: missense (70.6%), nonsense (14.3%), frameshift
      (8.7%), splicing (3.3%), in-frame deletions/insertions (1.8%), initiator
      methionine mutations (0.8%), and nonstop changes (0.5%). Mutation frequencies,
      positive rates, and the types of mutations were similar between tests performed
      by either Sanger (n = 17,377) or NGS (n = 503). Among patients with a positive
      genetic finding in a CMT-related gene, 94.9% were positive in one of four genes
      (PMP22, GJB1, MPZ, or MFN2). 

PMID- 25614875
TI  - Diagnosis of an imprinted-gene syndrome by a novel bioinformatics analysis of
      whole-genome sequences from a family trio.
AB  - Whole-genome sequencing and whole-exome sequencing are becoming more widely
      applied in clinical medicine to help diagnose rare genetic diseases.
      Identification of the underlying causative mutations by genome-wide sequencing is
      greatly facilitated by concurrent analysis of multiple family members, most often
      the mother-father-proband trio, using bioinformatics pipelines that filter
      genetic variants by mode of inheritance. However, current pipelines are limited
      to Mendelian inheritance patterns and do not specifically address disorders
      caused by mutations in imprinted genes, such as forms of Angelman syndrome and
      Beckwith-Wiedemann syndrome. Using publicly available tools, we implemented a
      genetic inheritance search mode to identify imprinted-gene mutations. Application
      of this search mode to whole-genome sequences from a family trio led to a
      diagnosis for a proband for whom extensive clinical testing and Mendelian
      inheritance-based sequence analysis were nondiagnostic. The condition in this
      patient, IMAGe syndrome, is likely caused by the heterozygous mutation c.832A>G
      (p.Lys278Glu) in the imprinted gene CDKN1C. The genotypes and disease status of
      six members of the family are consistent with maternal expression of the gene,
      and allele-biased expression was confirmed by RNA-Seq for the heterozygotes. This
      analysis demonstrates that an imprinted-gene search mode is a valuable addition
      to genome sequence analysis pipelines for identifying disease-causative variants.

PMID- 25614876
TI  - Complex genomic rearrangements in the dystrophin gene due to replication-based
      mechanisms.
AB  - Genomic rearrangements such as intragenic deletions and duplications are the most
      prevalent type of mutations in the dystrophin gene resulting in Duchenne and
      Becker muscular dystrophy (D/BMD). These copy number variations (CNVs) are
      nonrecurrent and can result from either nonhomologous end joining (NHEJ) or
      microhomology-mediated replication-dependent recombination (MMRDR). We
      characterized five DMD patients with complex genomic rearrangements using a
      combination of MLPA/mRNA transcript analysis/custom array comparative
      hybridization arrays (CGH) and breakpoint sequence analysis to investigate the
      mechanisms for these rearrangements. Two patients had complex rearrangements that
      involved microhomologies at breakpoints. One patient had a noncontiguous
      insertion of 89.7 kb chromosome 4 into intron 43 of DMD involving three
      breakpoints with 2-5 bp microhomology at the junctions. A second patient had an
      inversion of exon 44 flanked by intronic deletions with two breakpoint junctions
      each showing 2 bp microhomology. The third patient was a female with an inherited
      deletion of exon 47 in DMD on the maternal allele and a de novo noncontiguous
      duplication of exons 45-49 in DMD and MID1 on the paternal allele. The other two
      patients harbored complex noncontiguous duplications within the dystrophin gene.
      We propose a replication-based mechanisms for all five complex DMD
      rearrangements. This study identifies additional underlying mechanisms in DMD,
      and provides insight into the molecular bases of these genomic rearrangements. 

PMID- 25614879
TI  - A simple attitude control of quadrotor helicopter based on Ziegler-Nichols rules
      for tuning PD parameters.
AB  - An attitude control strategy based on Ziegler-Nichols rules for tuning PD
      (proportional-derivative) parameters of quadrotor helicopters is presented to
      solve the problem that quadrotor tends to be instable. This problem is caused by
      the narrow definition domain of attitude angles of quadrotor helicopters. The
      proposed controller is nonlinear and consists of a linear part and a nonlinear
      part. The linear part is a PD controller with PD parameters tuned by Ziegler
      Nichols rules and acts on the quadrotor decoupled linear system after feedback
      linearization; the nonlinear part is a feedback linearization item which converts
      a nonlinear system into a linear system. It can be seen from the simulation
      results that the attitude controller proposed in this paper is highly robust, and
      its control effect is better than the other two nonlinear controllers. The
      nonlinear parts of the other two nonlinear controllers are the same as the
      attitude controller proposed in this paper. The linear part involves a PID
      (proportional-integral-derivative) controller with the PID controller parameters
      tuned by Ziegler-Nichols rules and a PD controller with the PD controller
      parameters tuned by GA (genetic algorithms). Moreover, this attitude controller
      is simple and easy to implement. 

PMID- 25614878
TI  - Oral Health Disparities and Unmet Dental Needs among Preschool Children in
      Chelsea, MA: Exploring Mechanisms, Defining Solutions.
AB  - BACKGROUND: Significant disparities exist in children's receipt of preventive
      dental care (PDC) in the United States. Many of the children at greatest risk of
      dental disease do not receive timely PDC; when they do receive dental care, it is
      often more for relief of dental pain. Chelsea is a low-income, diverse
      Massachusetts community with high rates of untreated childhood caries. There are
      various dental resources available in Chelsea, yet many children do not access
      dental care at levels equivalent to their needs. OBJECTIVE: Using Chelsea as a
      case-study, to explore factors contributing to forgone PDC (including the age 1
      dental visit) in an in-depth way. METHODS: We used a qualitative study design
      that included semi-structured interviews with parents of preschool children
      residing in Chelsea, and Chelsea-based providers including pediatricians,
      dentists, a dental hygienist and early childhood care providers. We examined: a)
      parents' dental attitudes and oral health cultural beliefs; b) parents' and
      providers' perspectives on facilitators and barriers to PDC, reasons for unmet
      needs, and proposed solutions to address the problem. We recorded, transcribed
      and independently coded all interviews. Using rigorous, iterative qualitative
      data analyses procedures, we identified emergent themes. RESULTS: Factors
      perceived to facilitate receipt of PDC included Head-Start oral health policies,
      strong pediatric primary care/dental linkages, community outreach and
      advertising, and parents' own oral health experiences. Most parents and providers
      perceived there to be an adequate number of accessible dental services and
      resources in Chelsea, including for Medicaid enrollees. However, several barriers
      impeded children from receiving timely PDC, the most frequently cited being
      insurance related problems for children and adults. Other barriers included
      limited dental services for children <2 years, perceived poor quality of some
      dental practices, lack of emphasis on prevention-based dental care, poor care
      coordination, and insufficient culturally-appropriate care. Important family
      level barriers included parental oral health literacy, cultural factors, limited
      English proficiency and competing priorities. Several solutions were proposed to
      address identified barriers. CONCLUSION: Even in a community with a considerable
      number of dental resources, various factors may preclude access to these services
      by preschool-aged children. Opportunities exist to address modifiable factors
      through strategic oral health policies, community outreach and improved care
      coordination between physicians, dentists and early childhood care providers.

PMID- 25614880
TI  - Cutting a long story short? The clinical relevance of asking parents, nurses, and
      young children themselves to identify children's mental health problems by one or
      two questions.
AB  - BACKGROUND AND AIMS: Assessing young children's mental health is a crucial and
      challenging task. The aim of the study was to evaluate the clinical relevance of
      asking parents, nurses, and young children themselves to identify children's
      mental health problems by only one or two questions. METHODS: In regular health
      check-ups of 4- to 9-year-old children (n = 2682), parents and public health
      nurses assessed by one question whether the child had any emotional or behavioral
      difficulties. The child completed a self-evaluation enquiry on his/her emotional
      well-being. A stratified proportion of the participating parents were invited to
      a diagnostic interview. RESULTS: Sensitivities were fairly good for the parents'
      (68%), nurses' (65%), and their combined (79%) one-question screens. Difficulties
      identified by parents and nurses were major risks (OR 10-14) for any child
      psychiatric disorders (P < 0.001). The child's self-evaluation was related to 2
      fold to 3-fold risks (P < 0.05) for any psychiatric diagnosis, for any emotional
      diagnosis, and for negative situational factors. CONCLUSION: The one-question
      screen for parents and public health nurses together quite adequately identified
      the young children with mental health problems. The child's self-evaluation
      provided relevant and complementary information on his/her mental health and
      especially emotional problems.

PMID- 25614881
TI  - Bioethanol from lignocellulosic biomass: current findings determine research
      priorities.
AB  - "Second generation" bioethanol, with lignocellulose material as feedstock, is a
      promising alternative for first generation bioethanol. This paper provides an
      overview of the current status and reveals the bottlenecks that hamper its
      implementation. The current literature specifies a conversion of biomass to
      bioethanol of 30 to ~50% only. Novel processes increase the conversion yield to
      about 92% of the theoretical yield. New combined processes reduce both the number
      of operational steps and the production of inhibitors. Recent advances in
      genetically engineered microorganisms are promising for higher alcohol tolerance
      and conversion efficiency. By combining advanced systems and by intensive
      additional research to eliminate current bottlenecks, second generation
      bioethanol could surpass the traditional first generation processes. 

PMID- 25614882
TI  - Sauna-induced body mass loss in young sedentary women and men.
AB  - The aim of the study was to evaluate the relationship between body mass index
      (BMI) and body mass loss (BML) induced by thermal stress in a dry sauna. The
      study was conducted on a group of 674 sedentary students, 326 women and 348 men
      aged 19-20. The correlations between BMI scores and BML were determined. The
      subjects were placed in supine position in a dry sauna for two sessions of 10
      minutes each with a 5-minute break. The influence of BMI on the amount of BML in
      the sauna was determined by nonlinear stepwise regression. The smallest BML was
      noted in underweight subjects; students with normal weight lost more weight,
      whereas the greatest BML was reported in overweight and obese subjects. Persons
      with a high BMI are at higher risk of dehydration, and they should pay particular
      attention to replenishing fluids during a visit to the sauna. The proposed
      equations for calculating BML based on a person's BMI can be useful in estimating
      the amount of fluids that should be replenished by both men and women during a
      visit to a dry sauna. 

PMID- 25614883
TI  - The effect of land use change on transformation of relief and modification of
      soils in undulating loess area of East poland.
AB  - The change of primary forest areas into arable land involves the transformation
      of relief and modification of soils. In this study, we hypothesized that
      relatively flat loess area was largely transformed after the change of land use
      due to erosion. The modifications in soil pedons and distribution of soil
      properties were studied after 185 years of arable land use. Structure of pedons
      and solum depth were measured in 128 and soil texture and soil organic carbon in
      39 points. Results showed that soils of noneroded and eroded profiles occupied 14
      and 50%, respectively, and depositional soils 36% of the area. As a consequence,
      the clay, silt, and SOC concentration varied greatly in the plowed layer and
      subsoil. The reconstructed profiles of eroded soils and depositional soils
      without the accumulation were used to develop the map of past relief. The average
      inclination of slopes decreased from 4.3 to 2.2 degrees , and slopes >5 degrees 
      vanished in the present topography. Total erosion was 23.8 Mg ha(-1) year(-1).
      From that amount, 88% was deposited within the study area, and 12% was removed
      outside. The study confirmed the hypothesis of the significant effect of the land
      use change on relief and soils in loess areas.

PMID- 25614884
TI  - Balance ability and proprioception after single-bundle, single-bundle
      augmentation, and double-bundle ACL reconstruction.
AB  - PURPOSE: The present study sought to determine the influences of single-bundle
      (SB), single-bundle augmentation (SBA), and double-bundle (DB) reconstructions on
      balance ability and proprioceptive function. METHODS: 67 patients who underwent a
      single- or double-bundle ACL reconstruction or a SBA using multistranded
      autologous hamstring tendons were included in this study with a 1-year follow-up.
      Body sway and knee kinesthesia (using the threshold to detect passive motion test
      (TTDPM)) were measured to indicate balance ability and proprioceptive function,
      respectively. Additionally, within-subject differences in anterior-posterior
      stability of the tibia and lower extremity muscle strength were evaluated before
      and after surgery. RESULTS: At 6 and 12 months after surgery, DB reconstruction
      resulted in better balance and proprioceptive function than SB reconstruction (P
      < 0.05). Although no significant difference was observed in balance ability or
      proprioceptive function between the SBA and DB reconstructions, knee stability
      was significantly better with SBA and DB reconstructions than SB reconstruction
      (P < 0.05). No significant differences were found in quadriceps and hamstrings
      strength among the three reconstruction techniques. CONCLUSIONS: Our findings
      consider that joint stability, proprioceptive function, and balance ability were
      superior with SBA and DB reconstructions compared to SB reconstruction at 6 and
      12 months after surgery.

PMID- 25614885
TI  - Interrelation between patient satisfaction and patient-provider communication in
      diabetes management.
AB  - The present study aims to assess how patient satisfaction with medical provider
      patient communication can affect oral health, diabetes, and psychobehavioural
      measures among type 2 diabetes (T2DM) patients. It is part of a prospective
      intervention study among randomly selected T2DM patients, in Turkey. The data
      analyzed were Community Periodontal Need Index (CPI), HbA1c, patient satisfaction
      with communication, and psychobehavioural variables. Data was collected initially
      and at the end of the intervention. The participants were allocated to either
      health coaching (HC) or health education (HE). At baseline, there were no
      statistical differences between the HC and the HE groups on any of the measures
      (P > 0.05). Patients in both the HC and the HE groups had low satisfaction with
      communication. At postintervention, the increase in patient satisfaction with
      communication in the HC group was significantly higher than that in the HE group
      (P = 0.001). Principal component analysis revealed that patient satisfaction with
      communication shared the same cluster with clinical measures (CPI and HbA1c) and
      quality of life in the HC group. In conclusion, the present study showed, to our
      knowledge for the first time, that overall patient satisfaction with medical care
      provider-patient communication, empowered by HC approach, was interrelated with
      well-being of T2DM patients, in terms of psychobehavioural and clinical measures.

PMID- 25614886
TI  - A sequential statistical approach towards an optimized production of a broad
      spectrum bacteriocin substance from a soil bacterium Bacillus sp. YAS 1 strain.
AB  - Bacteriocins, ribosomally synthesized antimicrobial peptides, display potential
      applications in agriculture, medicine, and industry. The present study highlights
      integral statistical optimization and partial characterization of a bacteriocin
      substance from a soil bacterium taxonomically affiliated as Bacillus sp. YAS 1
      after biochemical and molecular identifications. A sequential statistical
      approach (Plackett-Burman and Box-Behnken) was employed to optimize bacteriocin
      (BAC YAS 1) production. Using optimal levels of three key determinants (yeast
      extract (0.48% (w/v), incubation time (62 hrs), and agitation speed (207 rpm)) in
      peptone yeast beef based production medium resulted in 1.6-fold enhancement in
      BAC YAS 1 level (470 AU/mL arbitrary units against Erwinia amylovora). BAC YAS 1
      showed activity over a wide range of pH (1-13) and temperature (45-80  degrees
      C). A wide spectrum antimicrobial activity of BAC YAS 1 against the human
      pathogens (Clostridium perfringens, Staphylococcus epidermidis, Campylobacter
      jejuni, Enterobacter aerogenes, Enterococcus sp., Proteus sp., Klebsiella sp.,
      and Salmonella typhimurium), the plant pathogen (E. amylovora), and the food
      spoiler (Listeria innocua) was demonstrated. On top and above, BAC YAS 1 showed
      no antimicrobial activity towards lactic acid bacteria (Lactobacillus bulgaricus,
      L. casei, L. lactis, and L. reuteri). Promising characteristics of BAC YAS 1
      prompt its commercialization for efficient utilization in several industries.

PMID- 25614887
TI  - Factors controlling carbon metabolism and humification in different soil
      agroecosystems.
AB  - The aim of this study was to describe the processes that control humic carbon
      sequestration in soil. Three experimental sites differing in terms of management
      system and climate were selected: (i) Abanilla-Spain, soil treated with municipal
      solid wastes in Mediterranean semiarid climate; (ii) Puch-Germany, soil under
      intensive tillage and conventional agriculture in continental climate; and (iii)
      Alberese-Italy, soil under organic and conventional agriculture in Mediterranean
      subarid climate. The chemical-structural and biochemical soil properties at the
      initial sampling time and one year later were evaluated. The soils under organic
      (Alberese, soil cultivated with Triticum durum Desf.) and nonintensive management
      practices (Puch, soil cultivated with Triticum aestivum L. and Avena sativa L.)
      showed higher enzymatically active humic carbon, total organic carbon,
      humification index (B/E(3)s), and metabolic potential (dehydrogenase
      activity/water soluble carbon) if compared with conventional agriculture and
      plough-based tillage, respectively. In Abanilla, the application of municipal
      solid wastes stimulated the specific beta-glucosidase activity (extracellular
      beta-glucosidase activity/extractable humic carbon) and promoted the increase of
      humic substances with respect to untreated soil. The evolution of the chemical
      and biochemical status of the soils along a climatic gradient suggested that the
      adoption of certain management practices could be very promising in increasing
      SOC sequestration potential.

PMID- 25614888
TI  - Plasticity of mesenchymal stem cells from mouse bone marrow in the presence of
      conditioned medium of the facial nerve and fibroblast growth factor-2.
AB  - A number of evidences show the influence of the growth of injured nerve fibers in
      peripheral nervous system as well as potential implant stem cells (SCs). The SCs
      implementation in the clinical field is promising and the understanding of
      proliferation and differentiation is essential. This study aimed to evaluate the
      plasticity of mesenchymal SCs from bone marrow of mice in the presence of culture
      medium conditioned with facial nerve explants and fibroblast growth factor-2 (FGF
      2). The growth and morphology were assessed for over 72 hours. Quantitative
      phenotypic analysis was taken from the immunocytochemistry for glial fibrillary
      acidic protein (GFAP), protein OX-42 (OX-42), protein associated with microtubule
      MAP-2 (MAP-2), protein beta-tubulin III (beta-tubulin III), neuronal nuclear
      protein (NeuN), and neurofilament 200 (NF-200). Cells cultured with conditioned
      medium alone or combined with FGF-2 showed morphological features apparently
      similar at certain times to neurons and glia and a significant proliferative
      activity in groups 2 and 4. Cells cultivated only with conditioned medium
      acquired a glial phenotype. Cells cultured with FGF-2 and conditioned medium
      expressed GFAP, OX-42, MAP-2, beta-tubulin III, NeuN, and NF-200. This study
      improves our understanding of the plasticity of mesenchymal cells and allows the
      search for better techniques with SCs. 

PMID- 25614890
TI  - Advanced mobility handover for mobile IPv6 based wireless networks.
AB  - We propose an Advanced Mobility Handover scheme (AMH) in this paper for seamless
      mobility in MIPv6-based wireless networks. In the proposed scheme, the mobile
      node utilizes a unique home IPv6 address developed to maintain communication with
      other corresponding nodes without a care-of-address during the roaming process.
      The IPv6 address for each MN during the first round of AMH process is uniquely
      identified by HA using the developed MN-ID field as a global permanent, which is
      identifying uniquely the IPv6 address of MN. Moreover, a temporary MN-ID is
      generated by access point each time an MN is associated with a particular AP and
      temporarily saved in a developed table inside the AP. When employing the AMH
      scheme, the handover process in the network layer is performed prior to its
      default time. That is, the mobility handover process in the network layer is
      tackled by a trigger developed AMH message to the next access point. Thus, a
      mobile node keeps communicating with the current access point while the network
      layer handover is executed by the next access point. The mathematical analyses
      and simulation results show that the proposed scheme performs better as compared
      with the existing approaches. 

PMID- 25614889
TI  - Serum levels of TNF- alpha , IL-12/23 p40, and IL-17 in psoriatic patients with
      and without nail psoriasis: a cross-sectional study.
AB  - Nail involvement has started playing a major role in the overall assessment and
      management of psoriatic disease. Biologics indicated for moderate to severe
      chronic plaque psoriasis are shown to be beneficial in nail disease. This study
      aimed to assess and compare the serum levels of TNF-alpha, IL-12/23 p40, and IL
      17 in psoriatic patients with and without nail involvement. 52 consecutively
      selected patients with chronic plaque psoriasis were included in this cross
      sectional study. Patients were studied and analyzed after they had been divided
      into 2 groups regarding the presence (n = 24) or not (n = 28) of nail psoriasis.
      The mean serum levels of TNF-alpha were significantly higher in the group of
      psoriatic patients with nail lesions compared to those without (t-test; 5.40 +/-
      1.17 versus 3.80 +/- 1.63, P = 0.026). However, the median serum levels of both
      IL-12/23 p40 (Mann-Whitney; 92.52 (34.35-126.87) versus 150.68 (35.18-185.86), P
      = 0.297) and IL-17 (Mann-Whitney; 28.49 (0.00-28.49) versus 8.59 (0.00-8.59), P =
      0.714) did not significantly differ between the 2 groups. These results confirm
      the important role of TNF-alpha in the pathogenesis of nail psoriasis and may
      suggest that anti-TNF agents could be more beneficial in psoriatic nail disease
      than agents targeting IL-12/23 p40 or IL-17 and its receptors. 

PMID- 25614891
TI  - Strategic wholesale pricing for an incumbent supplier facing with a competitive
      counterpart.
AB  - We introduce a wholesale pricing strategy for an incumbent supplier facing with a
      competitive counterpart. We propose a profit function which considers both the
      present loss and future loss from a wholesale price and then study the optimal
      wholesale prices for different objectives about this profit function for the
      incumbent supplier. First, we achieve an optimal wholesale price for the
      incumbent supplier to maximize his expected profit. Then, to reduce the risk
      originating from the fluctuation in the competitive supplier's wholesale price,
      we integrate the conditional value-at-risk (CVaR) measure in financial risk
      management into this study and derive an optimal wholesale price to maximize CVaR
      about profit for the incumbent supplier. Besides, the properties of the two
      optimal wholesale prices are discussed. Finally, some management insights are
      suggested for the incumbent supplier in a competitive setting. 

PMID- 25614892
TI  - Effects of different levels of coriander (Coriandrum sativum) seed powder and
      extract on serum biochemical parameters, microbiota, and immunity in broiler
      chicks.
AB  - The use of herbs and spices has gained increasing interest as feed additives and
      possible alternative to antibiotics in poultry production. The effects of using
      different levels of coriander seed powder or extract on selected blood
      parameters, intestinal microflora, and immune response of broiler chickens were
      investigated in this study. A total of 420-day-old broiler chicks were randomly
      assigned to 7 treatments with 4 replicates and fed for 42 days. Results showed
      that inclusion of 2.0% coriander powder in broiler diets lowered total
      cholesterol while blood urea was significantly higher in birds on T4 compared to
      T1 and T2. Furthermore, there were no treatment effects on Lactobacillus
      bacteria; however, the population of E. coli was significantly higher in the
      ileum of chickens fed T0. Noticeable significant improvements of antibody titer
      against Newcastle, infectious bronchitis, and infectious bursal disease were
      observed in birds receiving coriander extract in water. Immunoglobulin G antibody
      against sheep red blood cells showed significant improvement in birds fed T3;
      likewise, immunoglobulin M was significantly higher in birds on T2 and T3 at 28 d
      of age. These results revealed that coriander extract or powder can be used as
      antibiotic alternative in broiler feeds.

PMID- 25614893
TI  - Using multivariate geostatistics to assess patterns of spatial dependence of
      apparent soil electrical conductivity and selected soil properties.
AB  - The apparent soil electrical conductivity (ECa) was continuously recorded in
      three successive dates using electromagnetic induction in horizontal (ECa-H) and
      vertical (ECa-V) dipole modes at a 6 ha plot located in Northwestern Spain. One
      of the ECa data sets was used to devise an optimized sampling scheme consisting
      of 40 points. Soil was sampled at the 0.0-0.3 m depth, in these 40 points, and
      analyzed for sand, silt, and clay content; gravimetric water content; and
      electrical conductivity of saturated soil paste. Coefficients of correlation
      between ECa and gravimetric soil water content (0.685 for ECa-V and 0.649 for ECa
      H) were higher than those between ECa and clay content (ranging from 0.197 to
      0.495, when different ECa recording dates were taken into account). Ordinary and
      universal kriging have been used to assess the patterns of spatial variability of
      the ECa data sets recorded at successive dates and the analyzed soil properties.
      Ordinary and universal cokriging methods have improved the estimation of
      gravimetric soil water content using the data of ECa as secondary variable with
      respect to the use of ordinary kriging.

PMID- 25614894
TI  - Effect of catalytic pyrolysis conditions using pulse current heating method on
      pyrolysis products of wood biomass.
AB  - The influence of catalysts on the compositions of char and pyrolysis oil obtained
      by pyrolysis of wood biomass with pulse current heating was studied. The effects
      of catalysts on product compositions were analyzed using GC-MS and TEM. The
      compositions of some aromatic compounds changed noticeably when using a metal
      oxide species as the catalyst. The coexistence or dissolution of amorphous carbon
      and iron oxide was observed in char pyrolyzed at 800  degrees C with Fe3O4.
      Pyrolysis oil compositions changed remarkably when formed in the presence of a
      catalyst compared to that obtained from the uncatalyzed pyrolysis of wood meal.
      We observed a tendency toward an increase in the ratio of polyaromatic
      hydrocarbons in the pyrolysis oil composition after catalytic pyrolysis at 800 
      degrees C. Pyrolysis of biomass using pulse current heating and an adequate
      amount of catalyst is expected to yield a higher content of specific polyaromatic
      compounds.

PMID- 25614896
TI  - Cooperative control and its engineering applications in power systems.

PMID- 25614895
TI  - The effect of Angipars on diabetic neuropathy in STZ-induced diabetic male rats:
      a study on behavioral, electrophysiological, sciatic histological and
      ultrastructural indices.
AB  - Diabetes mellitus is the most common metabolic disease with a high prevalence
      rate in human society that eventually leads to the peripheral nervous system
      complications in a great number of patients. In the present study, the effects of
      Angipars on nerve conduction velocity, histological alterations, and behavioral
      indices were investigated. Diabetes was induced in male rats by intraperitoneal
      injection of streptozotocin (STZ). Six weeks after STZ injection, animals were
      divided into five groups control, vehicle, and 3 experimental groups. The vehicle
      group received 1 mL distilled water daily for two weeks and three experimental
      groups received, respectively, intraperitoneal injection of 5, 10, and 20 mg/kg
      Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some
      extent, could significantly improve behavioral indices of the experimental groups
      as compared to the vehicle group. Furthermore, mean nerve conduction velocity in
      the vehicle group showed significant difference with that in the control and the
      2nd experimental groups; therefore, Angipars could increase nerve conduction
      velocity in neuropathic rats. Overall, Angipars exerted positive effects on the
      treatment and reduction of physiologic symptoms and improvement of sciatic
      morphological injuries in neuropathic rats.

PMID- 25614897
TI  - Impacts of land use changes on soil properties and processes.

PMID- 25614898
TI  - Motor responses and weight gaining in neonates through use of two methods of
      earmuff and receiving silence in NICU.
AB  - BACKGROUND AND AIMS: With technological advances in NICUs the survival rate of
      preterm infants has been increased. Because NICU environment is a potent source
      of stress for infants, its modification is an essential measure to decrease
      infants' morbidity. The purposes of this study were to compare the effects of
      wearing earmuff and provision silence for infants on their motor responses and
      gaining weight. METHODS: In a randomized clinical trial 96 preterm infants were
      enrolled. Their motor responses were evaluated for two consecutive days in the
      morning and afternoon shifts, in the groups of earmuff and silence, and at
      similar time points in the control group. Also their weight was measured at days
      1 and 10. RESULTS: In the two intervention groups, means of motor responses in
      infants were significantly less than in the control group, and weight gain of
      infants was more than the control group. However weight gain was more pronounced
      in the earmuff group. CONCLUSION: Both interventions led to decreasing number of
      motor responses and improvement of weight gain pattern, but these effects were
      more pronounced in earmuff group; thus because implementation of silence in NICUs
      has many barriers, it is suggested to use earmuff for preterm infants in these
      units. This trial obtained IRCT registration number IRCT2012092010812N2.

PMID- 25614899
TI  - Low molecular weight heparin in portal vein thrombosis of cirrhotic patients:
      only therapeutic purposes?
AB  - Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the
      reduction in the hepatic synthesis of procoagulant proteins. However, with the
      progression of liver disease, the cirrhotic patient undergoes a high rate of
      thrombotic phenomena in the portal venous system. Although the progression of
      liver failure produces a reduction in the synthesis of anticoagulant molecules, a
      test able to detect the patients with hemostatic balance shifting towards
      hypercoagulability has not yet been elaborated. The need of treatment and/or
      prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the
      risk of bleeding from esophageal varices, and the mortality of liver
      transplantation, when portal vein thrombosis (PVT) occurs even if current
      guidelines do not give indications about PVT treatment in cirrhosis. In view of
      the general feeling that the majority of cirrhotic patients at an advanced stage
      may be in a procoagulant condition (suggested by the sharp increase in the
      prevalence of PVT), it is presumable that a prophylaxis of this population could
      be of benefit. The safety and the efficacy of prophylaxis and treatment with
      enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this
      option only in controlled trials and, currently, there are no sufficient
      evidences for a recommendation in the clinical practice. 

PMID- 25614900
TI  - rre37 Overexpression alters gene expression related to the tricarboxylic acid
      cycle and pyruvate metabolism in Synechocystis sp. PCC 6803.
AB  - The tricarboxylic acid (TCA) cycle and pyruvate metabolism of cyanobacteria are
      unique and important from the perspectives of biology and biotechnology research.
      Rre37, a response regulator induced by nitrogen depletion, activates gene
      expression related to sugar catabolism. Our previous microarray analysis has
      suggested that Rre37 controls the transcription of genes involved in sugar
      catabolism, pyruvate metabolism, and the TCA cycle. In this study, quantitative
      real-time PCR was used to measure the transcript levels of 12 TCA cycle genes and
      13 pyruvate metabolism genes. The transcripts of 6 genes (acnB, icd, ppc, pyk1,
      me, and pta) increased after 4 h of nitrogen depletion in the wild-type GT strain
      but the induction was abolished by rre37 overexpression. The repression of gene
      expression of fumC, ddh, and ackA caused by nitrogen depletion was abolished by
      rre37 overexpression. The expression of me was differently affected by rre37
      overexpression, compared to the other 24 genes. These results indicate that Rre37
      differently controls the genes of the TCA cycle and pyruvate metabolism, implying
      the key reaction of the primary in this unicellular cyanobacterium.

PMID- 25614901
TI  - Technology developments in structural health monitoring and integrity
      maintenance.

PMID- 25614902
TI  - Effects of Long-Term Supplementation of Blue-Green Algae on Lipid Metabolism in
      C57BL/6J mice.
AB  - Dyslipidemia is a primary risk factor for cardiovascular disease. In this study,
      we investigated the effect of long-term supplementation of two blue-green algae
      (BGA) species, i.e., Nostoc commune var. sphaeroides Kutzing (NO) and Spirulina
      platensis (SP), on lipid metabolism in vivo. Male C57BL/6J mice were fed an AIN
      93G/M diet supplemented with 2.5 or 5% (wt/wt) NO or SP for 6 months. Mice fed NO
      and SP showed lower plasma total cholesterol (TC) and triglyceride (TG)
      concentrations than control at certain months during 6 month experimental period.
      Both BGA supplementation for 6 months significantly increased hepatic TC contents
      whereas SP-fed groups had significantly less TG levels in the liver compared with
      control and NO groups. None of BGA-fed animals showed significantly different
      mRNA levels of sterol regulatory element binding protein 2, while 3-hydroxy-3
      methylglutaryl coenzyme A reductase and low-density lipoprotein receptor (LDLR)
      expression was higher in NO groups than the other groups in the liver.
      Furthermore, NO supplementation increased the hepatic expression of acetyl-CoA
      carboxylase 1, stearoyl CoA desaturase 1, carnitine palmitoyltransferase 1alpha,
      and acyl-CoA oxidase 1 but SP did not elicit any significant changes in mRNA
      levels of the genes compared with control. LDLR protein level was significantly
      higher in NO 2.5% and SP 5%, as compared to the control and NO 5% groups; while
      the level of fatty acid synthase protein in the liver was significantly higher in
      NO 5% and SP 5%, than that in the control group. In conclusion, our results
      suggest that long-term supplementation of NO and SP decreased plasma TC and TG
      concentrations. Therefore, supplementation of NO and SP may be potentially
      beneficial for preventing dyslipidemia-associated chronic diseases.

PMID- 25614904
TI  - Personalised medicine in psychiatry? Yes, but how?

PMID- 25614905
TI  - Chest x-ray quiz.

PMID- 25614903
TI  - A Perspective on Chromosomal Double Strand Break Markers in Mammalian Cells.

PMID- 25614906
TI  - Lifeline: Elizabeth Bradbury.
AB  - Elizabeth Bradbury is a Medical Research Council Senior Fellow at King's College
      London (London, UK). She trained as a neuroscientist at the Institute of
      Psychiatry and St Thomas' Hospital in London before becoming a group leader at
      King's in 2003. Her research focuses on understanding processes of injury and
      repair and developing therapies to restore function following CNS trauma, with a
      particular interest in glial scarring, extracellular matrix modification, and
      neuroplasticity after spinal cord injury.

PMID- 25614907
TI  - A very brief scientific reminiscence of John Gurdon.

PMID- 25614908
TI  - Sir John Gurdon and his contributions to understanding fundamental principles in
      developmental biology.

PMID- 25614909
TI  - Bruce P. Ryan (1932-2014) - A tribute.

PMID- 25614910
TI  - [Clinic diagnostic and treatment of various forms of a leukoplakia].

PMID- 25614911
TI  - Pieter van Zwieten (1937-2014).

PMID- 25614912
TI  - Department of Otorhinolaryngology at the Orenburg State Medical Academy (on the
      occasion of the 70th anniversary of the Orenburg State Medical Academy).

PMID- 25614913
TI  - [Treatment of depression: the current state and perspectives of the development
      of pharmacological studies].
AB  - A review of literature over the last two decades is presented. It is emphasized
      that psyachopharmacotherapy currently remains a main method of treatment of
      severe and moderate depression. Pharmacogenetic studies are directed mainly
      towards the identification of probable targets based on pharmacokinetcs and
      pharmacodynamics of andidepressants as well as the aspect of identification of
      probably predictors for treatment response.

PMID- 25614914
TI  - [Pharmacoeconomic aspects of using levodopa/carbidopa intestinal gel in
      Parkinson's disease].
AB  - The application of levodopa/carbidopa intestinal gel (LCIG), which provides the
      more reliable control of the disease and decrease in progression rates compared
      to standard treatment, is a variant of treatment of severe forms of Parkinson's
      disease. An analysis of pharmacoeconomic aspects of LCIG use in foreign countries
      has shown that this treatment significantly improves expectancy of patients and
      reduces the costs of professional care. The approximate threshold values of costs
      per 1 QALY recommended for reimbursement of intervention costs are L30,000 in the
      United Kingdom and ?50,000 in Sweden. In respect to intervention, LCIG can be
      regarded as an acceptable drug.

PMID- 25614915
TI  - Cone-beam computed tomography  imaging: therapeutic staff dose during 
      chemoembolisation procedure.
AB  - Cone-beam computed tomography (CBCT) imaging is an important requirement to
      perform real-time therapeutic image-guided procedures on patients. The purpose of
      this study is to estimate the personal-doseequivalent and annual-personal-dose
      from CBCT imaging during transarterial chemoembolisation (TACE). Therapeutic
      staff doses (therapeutic and assistant physician) were collected during 200
      patient (65 +/- 15 years, range: 40-86) CBCT examinations over six months.
      Absorbed doses were assessed using thermo-luminescent dosimeters during patient
      hepatic TACE therapy. We estimated personal-dose-equivalent (PDE) and annual
      personal-dose (APD) from absorbed dose based oninternational atomic energy agency
      protocol. APD for therapeutic procedure was calculated (therapeutic physician:
      5.6 mSv; assistant physician: 5.08 mSv) based on institutional work load.
      Regarding PDE, the hands of the staff members received a greater dose compared to
      other anatomical locations (therapeutic physician: 56 mSv, 72 mSv; assistant
      physician: 12 mSv, 14 mSv). Annual radiation doses to the eyes and hands of the
      staff members were lower compared to the prescribed limits by the International
      Commission on Radiological Protection (ICRP). PDE and APD of both therapeutic
      staff members were within the recommended ICRP-103 annual limit. Dose to the
      assistant physician waslower than the dose to the therapeutic physician during
      imaging. Annual radiation doses to eye-lenses and hands of both staff members
      were lower than prescribed limits.

PMID- 25614916
TI  - Stemming the flow of overseas nurses.

PMID- 25614917
TI  - Wanted: politically aware and involved nurses.

PMID- 25614918
TI  - Riding the Christchurch rollercoaster.

PMID- 25614919
TI  - Ag/FeCo/Ag core/shell/shell magnetic nanoparticles with plasmonic imaging
      capability.
AB  - Magnetic nanoparticles (NPs) have been used to separate various species such as
      bacteria, cells, and proteins. In this study, we synthesized Ag/FeCo/Ag
      core/shell/shell NPs designed for magnetic separation of subcellular components
      like intracellular vesicles. A benefit of these NPs is that their silver metal
      content allows plasmon scattering to be used as a tool to observe detection by
      the NPs easily and semipermanently. Therefore, these NPs are considered a
      potential alternative to existing fluorescent probes like dye molecules and
      colloidal quantum dots. In addition, the Ag core inside the NPs suppresses the
      oxidation of FeCo because of electron transfer from the Ag core to the FeCo
      shell, even though FeCo is typically susceptible to oxidation. The surfaces of
      the Ag/FeCo/Ag NPs were functionalized with epsilon-poly-L-lysine-based
      hydrophilic polymers to make them water-soluble and biocompatible. The imaging
      capability of the polymer-functionalized NPs induced by plasmon scattering from
      the Ag core was investigated. The response of the NPs to a magnetic field using
      liposomes as platforms and applying a magnetic field during observation by
      confocal laser scanning microscopy was assessed. The results of the
      magnetophoresis experiments of liposomes allowed us to calculate the magnetic
      force to which each liposome was subjected.

PMID- 25614920
TI  - Fluorophotometric Analysis of the Ocular Surface Glycocalyx in Soft Contact Lens
      Wearers.
AB  - PURPOSE: Unstable tear film characterized by shorting of tear break-up time (BUT)
      is associated with discomfort and dryness in contact lens wearers. The glycocalyx
      is thought to be crucial in maintaining the wettability and lubrication of the
      ocular surface. We evaluated the ocular surface glycocalyx in soft contact lens
      (SCL) wearers using a fluorescein-labeled wheat germ agglutinin (F-WGA) as a
      marker to demonstrate the ocular surface glycoconjugates in vivo. METHODS: Twenty
      experienced SCL wearers and 20 healthy volunteers with no history of CL wearing
      (controls) were enrolled in the study. After applying a 5% F-WGA solution to the
      eyes of study individuals, fluorescent intensities in their respective central
      corneas were measured by fluorophotometry. The relationship between F-WGA
      intensity in the corneal surface and clinical parameters associated with contact
      lens wear were analyzed. RESULTS: F-WGA fluorescence intensity in the SCL group
      was 418.5 +/- 103.3, which was significantly lower than that of the controls
      (825.0 +/- 179.8; p < 0.0001, Mann-Whitney test). F-WGA fluorescence intensity
      was not correlated with Schirmer's test values or age, whereas a statistically
      significant correlation between F-WGA fluorescence intensity and tear film BUT
      was observed (r = 0.77, p < 0.0001). The decrease in F-WGA fluorescence intensity
      could be reversed by discontinuation of SCL use. CONCLUSION: Reduction and/or
      compositional alteration of ocular surface glycocalyx may be one of the causative
      factors of SCL-induced eye dryness.

PMID- 25614921
TI  - Parathyroid hormone-related protein-induced hypercalcemia due to osteosarcoma in
      a cat.
AB  - A 15-year-old castrated male mixed-breed cat was presented with a history of
      sarcoma of the distal right hind limb. Biochemical analysis revealed increased
      concentrations of blood urea, creatinine, total calcium, ionized calcium, and
      parathyroid hormone-related protein (PTHrP). The mass was removed surgically by
      amputation of the hind limb. Osteosarcoma was diagnosed based on histopathologic
      examination. All abnormal serum analyte concentrations improved immediately after
      surgery, including azotemia, total calcium, ionized calcium, and PTHrP. The
      biochemical results were attributed to osteosarcoma causing PTHrP-induced
      hypercalcemia. 

PMID- 25614922
TI  - Fully substituted pyranones via quasi-heterogeneous genuinely ligand-free Migita
      Stille coupling of iodoacrylates.
AB  - Migita-Stille coupling of (Z)-beta-iodoacrylates with (E)-alpha-stannyl allylic
      alcohols to furnish 5-alkylidene-4-substituted-5,6-dihydro-2H-pyran-2-ones is
      efficiently catalyzed by 2% Pd black in DMF, while Pd(PPh3)4 is inactive.
      Heterogeneous Pd released in solution is most likely responsible for the
      catalysis. The reaction is applicable to other substrates, without having to
      resort to ligands, additives, and/or solid support for Pd. The resulting
      pyranones can be rearranged to fully functionalized pyranones in another single
      step. 

PMID- 25614923
TI  - Modeling environmental contamination in hospital single- and four-bed rooms.
AB  - Aerial dispersion of pathogens is recognized as a potential transmission route
      for hospital acquired infections; however, little is known about the link between
      healthcare worker (HCW) contacts' with contaminated surfaces, the transmission of
      infections and hospital room design. We combine computational fluid dynamics
      (CFD) simulations of bioaerosol deposition with a validated probabilistic HCW
      surface contact model to estimate the relative quantity of pathogens accrued on
      hands during six types of care procedures in two room types. Results demonstrate
      that care type is most influential (P < 0.001), followed by the number of surface
      contacts (P < 0.001) and the distribution of surface pathogens (P = 0.05).
      Highest hand contamination was predicted during Personal care despite the highest
      levels of hand hygiene. Ventilation rates of 6 ac/h vs. 4 ac/h showed only minor
      reductions in predicted hand colonization. Pathogens accrued on hands decreased
      monotonically after patient care in single rooms due to the physical barrier of
      bioaerosol transmission between rooms and subsequent hand sanitation. Conversely,
      contamination was predicted to increase during contact with patients in four-bed
      rooms due to spatial spread of pathogens. Location of the infectious patient with
      respect to ventilation played a key role in determining pathogen loadings (P =
      0.05). PRACTICAL IMPLICATIONS: We present the first quantitative model predicting
      the surface contacts by HCW and the subsequent accretion of pathogenic material
      as they perform standard patient care. This model indicates that single rooms may
      significantly reduce the risk of cross-contamination due to indirect infection
      transmission. Not all care types pose the same risks to patients, and
      housekeeping performed by HCWs may be an important contribution in the
      transmission of pathogens between patients. Ventilation rates and positioning of
      infectious patients within four-bed rooms can mitigate the accretion of
      pathogens, whereby reducing the risk of missed hand hygiene opportunities. The
      model provides a tool to quantitatively evaluate the influence of hospital room
      design on infection risk.

PMID- 25614924
TI  - Development of MijnAVL, an Interactive Portal to Empower Breast and Lung Cancer
      Survivors: An Iterative, Multi-Stakeholder Approach.
AB  - BACKGROUND: MijnAVL (MyAVL) is an interactive portal being developed to empower
      cancer survivors. Literature review and focus groups yielded the selection of
      features such as access to the electronic medical record (EMR), patient reported
      outcomes (PROs) and related feedback, and a physical activity support program.
      OBJECTIVE: Our aim was to present a final design of MijnAVL based on (1) health
      professionals' evaluation of proposed features, (2) cancer survivors' evaluation
      of a first draft, and (3) cancer survivors' evaluation of a functional online
      prototype. METHODS: Professionals from various disciplines gave input to the
      content of and procedures related to MijnAVL. Subsequently, 16 cancer survivors
      participated in an interview to evaluate content and graphic design of a first
      draft (shown with screenshots). Finally, 7 survivors participated in a usability
      test with a fully functional prototype. They performed predefined tasks (eg,
      logging in, finding a test result, completing a questionnaire) while thinking
      aloud. Descriptive statistics and simple content analysis were used to analyze
      the data of both the interviews and the usability tests. RESULTS: Professionals
      supported access to the EMR (eg, histology reports, lab results, and their
      letters to general practitioners). They also informed the development of PROs and
      the physical activity support program. Based on the first draft, survivors
      selected the preferred graphic design, approved the features and provided
      suggestions for the content (eg, explanation of medical jargon, more concise
      texts, notification by emails). Usability tests revealed that it was relatively
      easy to navigate the website and use the different features. Recommendations
      included, among others, a frequently asked questions section and the use of
      hyperlinks between different parts of the website. CONCLUSIONS: The development
      of MijnAVL, an interactive portal to empower breast and lung cancer survivors,
      was performed iteratively and involved multiple groups of end-users. This
      approach resulted in a usable and understandable final version. Its effectiveness
      should be determined in further research.

PMID- 25614925
TI  - Heteroaggregation of graphene oxide with minerals in aqueous phase.
AB  - Upon release into waters, sediments, and soils, graphene oxide (GO) may interact
      with fine mineral particles. We investigated the heteroaggregation of GO with
      different minerals, including montmorillonite, kaolinite, and goethite, in
      aqueous phase. GO significantly enhanced the dispersion of positively charged
      goethite (>50%) via heteroaggregation, while there was no interaction between GO
      and negatively charged montmorillonite or kaolinite. Electrostatic attraction was
      the dominant force in the GO-goethite heteroaggregation (pH 4.0-8.5), and the
      dissolved Fe ions (<0.16 mg/L) from goethite were unable to destabilize GO
      suspension. The GO-goethite heteroaggregation was further quantitatively
      investigated through GO adsorption study. All adsorption isotherms of GO at
      different solution pH (4.0 and 6.5) followed the Linear model. The apparent
      intercept (1.0-6.9 mg/g) was observed for all the adsorption isotherms,
      indicating that this fraction of adsorbed GO was difficult to desorb from
      goethite (defined here as irreversible adsorption) under the tested conditions.
      Desorption hysteresis was observed, which could be explained by the formation of
      multilayered GO-goethite complex with high configurational stability. These
      findings are useful for understanding the interaction of GO with mineral
      surfaces, and potential fate and toxicity of GO under natural conditions in
      aquatic environments, as well as in soils and sediments. 

PMID- 25614926
TI  - Mycorrhizal networks and coexistence in species-rich orchid communities.
AB  - Multispecies assemblages often consist of a complex network of interactions.
      Describing the architecture of these networks is a first step in understanding
      the stability and persistence of these species-rich communities. Whereas a large
      body of research has been devoted to the description of above-ground
      interactions, much less attention has been paid to below-ground interactions,
      probably because of difficulties to adequately assess the nature and diversity of
      interactions occurring below the ground. In this study, we used 454 amplicon
      pyrosequencing to investigate the architecture of the network between mycorrhizal
      fungi and 20 orchid species co-occurring in a species-rich Mediterranean
      grasslands. We found 100 different fungal operational taxonomic units (OTUs)
      known to be mycorrhizal in orchids, most of which were members related to the
      genera Ceratobasidium and Tulasnella. The network of interactions was
      significantly compartmentalized (M = 0.589, P = 0.001), but not significantly
      nested (N = 0.74, NODF = 10.58; P > 0.05). Relative nestedness was negative (N* =
      -0.014), also suggesting the existence of isolated groups of interacting species.
      Compartmentalization is a typical feature of ecological systems showing high
      interaction intimacy, and may reflect strong specialization between orchids and
      fungi resulting from physiological, physical or spatial constraints. 

PMID- 25614927
TI  - Characterization of fine mode atmospheric aerosols by Raman microscopy and
      diffuse reflectance FTIR.
AB  - A combination of Raman microscopy and diffuse reflectance Fourier transform
      infrared spectroscopy (FTIR) has been used for the characterization of fine mode
      (<1 MUm) tropospheric aerosols. Peak fitting was used to identify five
      overlapping bands in the Raman spectra. These bands have been identified as due
      to combustion generated carbon soot as well as large molecular organic carbon
      species. The fwhm of the D band at 1400 cm(-1) as well as the ratio of
      intensities of the D3 band at 1550 cm(-1) to the G band at 1580 cm(-1) can serve
      as a measure of the aerosol organic carbon content. Raman microscopy combined
      with spectral mapping capabilities was used to investigate the composition of the
      fine mode aerosols at the particle level, allowing for the direct determination
      of aerosol mixing state. Results showed that the fine aerosols were predominately
      internally mixed particles composed of carbon soot coated with molecular organic
      carbon species. Characterization of the aerosols by diffuse reflectance FTIR
      showed that the major organic carbon species were polycarboxylates and
      polysaccharide-like species typical of humic-like substances (HULIS). 

PMID- 25614928
TI  - Risk factors for gestational diabetes mellitus: ethnic disparities.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) increases the risk of poor
      maternal and infant health outcomes; therefore, the objective of this study was
      to compare the ethnic disparities and identify the risk factors for GDM. DESIGN:
      We performed a cross-sectional analysis using patient records from a hospital
      located in the Puli area of Central Taiwan. SETTING: A teaching hospital located
      in a rural mountainous area of Central Taiwan. PARTICIPANTS: Between 2002 and
      2012, the hospital admitted 154 patients (107 non-aborigines, 30 aborigines, and
      17 non-Taiwanese) who exhibited glucose intolerance during their pregnancy. MAIN
      OUTCOME MEASURES: GDM was confirmed using the oral-glucose-tolerance-test
      administered in dose of either 100 g or 75 g. The incidence and risk factors for
      GDM in the aboriginal and non-aboriginal women was compared. RESULTS: We excluded
      the patients who had overt diabetes or were non-Taiwanese. Thus, 132 patients (28
      aboriginal and 104 non-aboriginal women; mean age 30 years) were enrolled in the
      final study. A total of 51 patients (15 aboriginal, 36 non-aboriginal women) had
      GDM, which was more prevalent among the aboriginal mothers (53.6% versus 34.6%).
      The risk factors for GDM among the aboriginal women were persistent glycosuria
      and prior macrosomia. CONCLUSION: The Taiwanese aboriginal women exhibited higher
      incidence of GDM; thus, we recommend that early screening and health education
      for pregnant aboriginal women be provided.

PMID- 25614929
TI  - Performance of fluorescence-based methods for detecting and quantifying smooth
      surface caries lesions in primary teeth: an in vitro study.
AB  - BACKGROUND: Although smooth-surface caries can be subjectively assessed by visual
      inspection, quantitative methods would improve the monitoring of these lesions.
      AIM: To evaluate the in vitro performance of laser fluorescence devices, namely
      DIAGNOdent (LF) and DIAGNOdent pen (LFpen), and a fluorescence camera
      (VistaProof; FC) in the detection and quantification of smooth-surface caries in
      primary teeth. DESIGN: Two examiners evaluated 99 smooth surfaces of 65 extracted
      primary molars using FC, LF, and LFpen. As a reference standard, the actual and
      relative lesion depths were determined using stereomicroscopy and polarized light
      microscopy. Reproducibilities were assessed, and correlation analyses were
      performed. The sensitivities, specificities, and accuracies of the methods were
      calculated and compared. RESULTS: There was a significant correlation between the
      values obtained using the fluorescence-based devices and the actual and relative
      lesion depths, although the correlation coefficient values were not higher than
      0.7 (LF, 0.673; LFpen, 0.646; FC, 0.663). The sensitivities of the devices were
      similar for the detection of enamel caries, although LFpen was superior in
      detecting dentin lesions. The reliabilities of all methods were moderate to low,
      with similar accuracies at all depths. CONCLUSION: Although the fluorescence
      based devices showed similar performance in the detection of enamel and dentin
      lesions, the reliability of these devices and the correlation of their findings
      with the actual and relative lesion depths were moderate with regard to smooth
      surface caries in primary molars.

PMID- 25614930
TI  - Preparation, in-vitro and in-vivo evaluation of spray-dried ternary solid
      dispersion of biopharmaceutics classification system class II model drug.
AB  - OBJECTIVES: The objective of this study was to investigate the impact of a novel
      spray-dried ternary solid dispersion (TSD) on the dissolution rate and
      bioavailability of a biopharmaceutics classification system (BCS) class II model
      drug, atorvastatin calcium trihydrate (ATC), and evaluate its in-vitro and in
      vivo performance. METHODS: TSD of ATC was prepared by spray-drying method
      employing ethanol/water solvent systems. The TSD formulations, composed of
      hydroxypropyl methylcellulose (HPMC E5) and nicotinamide, were optimized by
      rotatable central composite design. Physicochemical characterization along with
      dissolution, stability and pharmacokinetic study of optimized TSD was evaluated.
      KEY FINDINGS: The optimized TSD was found to be amorphous with spherical shape
      morphology. It exhibited a fourfold increase in dissolution rate in comparison to
      ATC, with a considerable enhancement in oral bioavailability (relative
      bioavailability of 134.11%). Physicochemical characterization and dissolution
      study of optimized TSD at the end of stability studies clearly indicated that the
      stability of optimized TSD was due to hydrogen bonding between drug and HPMC E5
      and nicotinamide. This bonding remained unaffected even under stressful
      conditions of high temperature and humidity. CONCLUSION: The TSD exhibits a
      significant increase in dissolution rate, and for this reason should be useful as
      an efficacious tool to enhance the bioavailability of BCS class II drug molecule,
      ATC.

PMID- 25614931
TI  - Room-temperature ballistic transport in III-nitride heterostructures.
AB  - Room-temperature (RT) ballistic transport of electrons is experimentally observed
      and theoretically investigated in III-nitrides. This has been largely
      investigated at low temperatures in low band gap III-V materials due to their
      high electron mobilities. However, their application to RT ballistic devices is
      limited by their low optical phonon energies, close to KT at 300 K. In addition,
      the short electron mean-free-path at RT requires nanoscale devices for which
      surface effects are a limitation in these materials. We explore the unique
      properties of wide band-gap III-nitride semiconductors to demonstrate RT
      ballistic devices. A theoretical model is proposed to corroborate experimentally
      their optical phonon energy of 92 meV, which is ~4* larger than in other III-V
      semiconductors. This allows RT ballistic devices operating at larger voltages and
      currents. An additional model is described to determine experimentally a
      characteristic dimension for ballistic transport of 188 nm. Another remarkable
      property is their short carrier depletion at device sidewalls, down to 13 nm,
      which allows top-down nanofabrication of very narrow ballistic devices. These
      results open a wealth of new systems and basic transport studies possible at RT. 

PMID- 25614932
TI  - Can preoperative cranial ultrasound predict early neurodevelopmental outcome in
      infants with congenital heart disease?
AB  - AIM: To determine the role of preoperative cranial ultrasound (cUS) in predicting
      neurodevelopmental outcome in infants undergoing bypass surgery for congenital
      heart disease (CHD). METHOD: Prospective cohort study on 77 infants (44 males, 33
      females) operated before 3 months of age (median age at surgery 10d [range 3
      88d]) who received at least one preoperative cUS. Outcome at 1 year was assessed
      with a standardized neurological examination and the Bayley Scales of Infant
      Development II (mental developmental index [MDI]; psychomotor developmental index
      [PDI]). RESULTS: Abnormalities on cUS were detected in 22 (29%) infants and
      consisted of diffuse brain oedema (n=12, 16%), periventricular white matter
      injury (n=5, 6%), ventricular dilatation (n=3, 4%), and intraventricular
      haemorrhage (IVH) (n=2, 3%). Infants undergoing balloon-atrial septostomy (BAS)
      had a higher rate of subsequent brain oedema than those without BAS (p=0.006).
      cUS abnormalities were not related to neurodevelopmental outcome. INTERPRETATION:
      Preoperative cUS findings in infants undergoing bypass surgery for CHD occur
      rather frequently, consisting of mild lesions such as brain oedema or white
      matter changes. These findings, however, do not correlate with early
      neurodevelopmental outcome.

PMID- 25614933
TI  - Chronology of confluent and reticulated papillomatosis: spontaneous regression in
      a case after long-term follow-up may imply transient nature of the condition.

PMID- 25614934
TI  - The Tomato Glycoalkaloid alpha-Tomatine Induces Caspase-Independent Cell Death in
      Mouse Colon Cancer CT-26 Cells and Transplanted Tumors in Mice.
AB  - Tomatoes (Solanum lycopersicum) produce the bioactive glycoalkaloid alpha
      tomatine. This study determined the effect of commercial alpha-tomatine on CT-26
      colon cancer cells in vitro and in vivo in an intracutaneously transplanted mouse
      tumor. Cytotoxicity experiments showed that alpha-tomatine induces about 50%
      lysis of the colon cancer cells at 3.5 MUM after 24 h of treatment. Large
      proportions of cells were found to be in the annexin V (+)/propidium iodide (+)
      phase of cell death, implying late phase apoptotic/necrotic status. However,
      alpha-tomatine induced cell death in CT-26 cancer cells through caspase
      independent signaling pathways. This conclusion was supported by Western blot
      analysis showing a localization of apoptosis-inducing mitochondrial protein (AIF)
      to the nucleus and down-regulation of survivin (an inhibitor of apoptosis)
      expression as well as failure to detect the active form of caspase-3, -8, and -9
      produced by proteolytic cleavage in CT-26 cancer cells. Intraperitoneally
      administered alpha-tomatine (5 mg/kg body weight) also markedly inhibited growth
      of the tumor using CT-26 cancer cells without causing body and organ weight
      changes. The reduced tumor growth in the mice by 38% after 2 weeks was the result
      of increased caspase-independent apoptosis associated with increased nuclear
      translocation of AIF and decreased survivin expression in tumor tissues. alpha
      Tomatine in pure form and in tomatine-rich green tomatoes might prevent colon
      cancer.

PMID- 25614935
TI  - CBTF: new amine-to-thiol coupling reagent for preparation of antibody conjugates
      with increased plasma stability.
AB  - Amine-to-thiol coupling is the most common route for the preparation of antibody
      drug conjugates (ADC). It is usually achieved by using heterobifunctional
      reagents possessing an activated ester at one end and a maleimide group at the
      other. However, maleimide-based conjugates were recently revealed to have limited
      stability in blood circulation, which can compromise therapeutic efficacy of the
      conjugate. To address this issue, we have developed a heterobifunctional reagent,
      sodium 4-((4-(cyanoethynyl)benzoyl)oxy)-2,3,5,6-tetrafluorobenzenesulfonate
      (CBTF), for amine-to-thiol coupling. It comprises a recently described 3
      arylpropionitrile (APN) function in replacement of maleimide and allows for the
      preparation of remarkably stable conjugates. A series of antibody-dye conjugates
      have been prepared using this reagent and shown superior stability in human blood
      plasma compared to maleimide-derived conjugates. 

PMID- 25614936
TI  - Polarization-sensitive sum-frequency generation microscopy of collagen fibers.
AB  - Point-scanning sum-frequency generation (SFG) microscopy enables the generation
      of images of collagen I fibers in tissues by tuning into specific vibrational
      resonances of the polypeptide. It is shown that when collagen-rich tissues are
      visualized near the 2954 cm(-1) stretching vibration of methylene groups, the SFG
      image contrast is higher compared to the contrast seen in nonresonant second
      harmonic generation (SHG) imaging. Polarization and spectrally resolved analysis
      of the SFG signal as a function of fiber orientation in the CH-stretching range
      of the vibrational spectrum enabled a comparative characterization of the achiral
      tensor elements of collagen's second-order susceptibility. This analysis reveals
      that selected on-resonance tensor elements are enhanced over other elements,
      giving rise to a much stronger anisotropy rho of the signal for SFG (rho ~ 15)
      compared to SHG (rho ~ 3). The improved anisotropy of the vibrationally resonant
      signal contributes to the higher contrast seen in the SFG tissue images. 

PMID- 25614937
TI  - Printing small dots from large drops.
AB  - Printing of droplets of pure solvents containing suspended solids typically leads
      to a ring stain due to convective transport of the particles toward the contact
      line during evaporation of the solvent. In mixtures of volatile solvents,
      recirculating cells driven by surface tension gradients are established that lead
      to migration of colloidal particles toward the center of the droplet. In
      favorable cases, a dense disk of particles forms with a diameter much smaller
      than that of the droplet. In the latter stages of drying, convective transport of
      the particles radially toward the contact line still occurs. Two strategies are
      described to fix the distribution of particles in a compact disk much smaller
      than the initial diameter of the drying droplet. First, a nanoparticulate clay is
      added to induce an evaporation-driven sol-gel transition that inhibits convective
      flow during the latter stages of drying. Second, a nonadsorbing polymer is added
      to induce depletion flocculation that restricts particle motion after the
      particles have been concentrated near the center of the droplet. The area of the
      resulting deposit can be as little as 10% of the footprint of the printed
      droplet. 

PMID- 25614938
TI  - Concurrent validity of the MOX activity monitor compared to the ActiGraph GT3X.
AB  - BACKGROUND: The It's LiFe! monitoring and feedback tool embedded in primary care
      practice is promising in helping people to achieve an active lifestyle. This new
      tool consists of an activity monitor (the MOX), which is connected to a
      smartphone application and to a Web service for patients and care providers. The
      aim of this study was to develop thresholds for the moderate and vigorous
      activity categories and examine the concurrent validity of the MOX in relation to
      the ActiGraph (Pensacola, FL) GT3X in healthy participants and chronically ill
      patients (chronic obstructive pulmonary disease and type 2 diabetes) in a
      laboratory situation and during daily living. MATERIALS AND METHODS: Participants
      wore the two activity monitors simultaneously on the lower back. An incremental
      treadmill protocol was executed by 8 healthy adults and 10 patients. For daily
      living measurements, 15 healthy adults and 12 patients wore the devices for 6-7
      days. Daily living data were corrected for non-wear time, using diary
      information. RESULTS: On the treadmill there was an excellent correlation between
      the ActiGraph and MOX counts (mean r=0.99 in healthy participants and mean r=0.98
      in patients). Correlation during daily living was moderate (mean r=0.72) in
      healthy adults and good (mean r=0.82) in patients. Bland-Altman plots showed no
      perfect agreement between the two devices in minutes per category. However, a
      histogram of misclassified minutes showed that misclassification occurred around
      category thresholds. CONCLUSIONS: The MOX is capable of measuring physical
      activity and can be used in the It's LiFe!

PMID- 25614939
TI  - A new era of ventricular assist device surgery: less invasive procedures.
AB  - As the number of patients suffering of congestive heart failure is rising
      worldwide, the use of mechanical circulatory support to treat these patients has
      also grown enormously, surpassing the number of annual heart transplants.
      Moreover latest generation of left ventricular assist devices (LVADs) is
      characterized by improved technologies. Moreover the size of new LVAD systems is
      considerably reduced when compared to older generation devices. Therefore, less
      invasive surgery is now possible for the implantation, explantation, and exchange
      of LVADs. Although experience with these new techniques is still limited,
      minimally invasive procedures are thought to improve surgical outcomes by
      declining the rates of operative complications such as bleeding or wound
      infection. The miniaturization of LVADs will continue, so that minimally invasive
      techniques will be used for most LVAD-related procedures in the future. In this
      article, we summarize and describe minimally invasive surgical techniques, with a
      focus on the most common LVAD systems in adults. 

PMID- 25614940
TI  - Looking into the "Garden of the Hesperides": new drugs for hepatocellular
      carcinoma.
AB  - Advanced hepatocellular carcinoma remains an entity that is hard to approach
      therapeutically and has shown disappointing results in terms of survival. For
      many years, the only accepted option for this setting was the use of a
      multikinase inhibitor, sorafenib. Nevertheless, through the years, a deeper
      knowledge has arisen about how pathogenic pathways correlate with hepatocellular
      carcinoma. In this review, we provide an update of the most recent data regarding
      new agents under investigation and new possible targets for future treatments. 

PMID- 25614941
TI  - Dimethylfumarate alleviates early brain injury and secondary cognitive deficits
      after experimental subarachnoid hemorrhage via activation of Keap1-Nrf2-ARE
      system.
AB  - OBJECT: Oxidative stress and the inflammatory response are thought to promote
      brain damage in the setting of subarachnoid hemorrhage (SAH). Previous reports
      have shown that dimethylfumarate (DMF) can activate the Kelch-like ECH-associated
      protein 1-nuclear factor erythroid 2-related factor 2-antioxidant-responsive
      element (Keap1-Nrf2-ARE) system in vivo and in vitro, which leads to the
      downregulation of oxidative stress and inflammation. The aim of this study was to
      evaluate the potential neuroprotective effect of DMF on SAH-induced brain injury
      in rats. METHODS: Rats were subjected to SAH by the injection of 300 MUl of
      autologous blood into the chiasmatic cistern. Rats in a DMF-treated group were
      given 15 mg/kg DMF twice daily by oral gavage for 2 days after the onset of SAH.
      Cortical apoptosis, neural necrosis, brain edema, blood-brain barrier impairment,
      learning deficits, and changes in the Keap1-Nrf2-ARE pathway were assessed.
      RESULTS: Administration of DMF significantly ameliorated the early brain injury
      and learning deficits induced by SAH in this animal model. Treatment with DMF
      markedly upregulated the expressions of agents related to Keap1-Nrf2-ARE
      signaling after SAH. The inflammatory response and oxidative stress were
      downregulated by DMF therapy. CONCLUSIONS: DMF administration resulted in
      abatement of the development of early brain injury and cognitive dysfunction in
      this prechiasmatic cistern SAH model. This result was probably mediated by the
      effect of DMF on the Keap1-Nrf2-ARE system.

PMID- 25614942
TI  - Parasellar xanthogranulomas.
AB  - OBJECT: Xanthogranulomas are rare inflammatory masses most often found in the
      skin and eye. The incidence of intracranial xanthogranulomas is 1.6%-7%, with
      those found in the sellar and parasellar region being exceedingly rare and their
      etiology controversial. Sellar and parasellar xanthogranulomas are rarely
      reported in the western hemisphere, and their incidence in Western countries is
      unknown. METHODS: A prospectively acquired database of all endonasal endoscopic
      transsphenoidal surgeries performed at Weill Cornell Medical College was queried.
      Patients with histologically confirmed xanthogranulomas who were diagnosed and
      treated between 2003 and 2013 were included in the study. Patient history,
      demographic data, histological findings, and surgical approach were also
      evaluated. RESULTS: A total of 643 endonasal endoscopic procedures had been
      performed at the time of this study. Four patients (0.6%) were identified as
      having a histologically confirmed xanthogranuloma of the parasellar region,
      compared with an incidence of 6.7% for craniopharyngioma (CP) and 2% for Rathke
      cleft cyst (RCC). The most common symptom was visual loss, followed by headache.
      Preoperative diagnosis was CP in all cases. All patients underwent extended
      endonasal endoscopic transsphenoidal surgery with gross-total resection. Two
      patients developed panhypopituitarism after surgery. There were no CSF leaks. The
      mean follow-up was 61 months, at which time there were no recurrences. The key
      histological features differentiating xanthogranulomas from CPs were accumulation
      of foamy macrophages, multinucleated foreign body giant cells, cholesterol
      clefts, and hemosiderin deposits without stratified squamous epithelium. These
      histological features appear commonly as part of the spectrum of a secondary
      inflammatory response in an RCC. CONCLUSIONS: Parasellar xanthogranulomas most
      closely approximate CPs clinically but pathological evidence may suggest an RCC
      origin. Gross-total resection can be achieved through extended endonasal
      endoscopic transsphenoidal approaches, and is curative.

PMID- 25614943
TI  - Publication productivity of neurosurgeons in Great Britain and Ireland.
AB  - OBJECT: Bibliometrics are the methods used to quantitatively analyze scientific
      literature. In this study, bibliometrics were used to quantify the scientific
      output of neurosurgical departments throughout Great Britain and Ireland.
      METHODS: A list of neurosurgical departments was obtained from the Society of
      British Neurological Surgeons website. Individual departments were contacted for
      an up-to-date list of consultant (attending) neurosurgeons practicing in these
      departments. Scopus was used to determine the h-index and m-quotient for each
      neurosurgeon. Indices were measured by surgeon and by departmental mean and
      total. Additional information was collected about the surgeon's sex, title,
      listed superspecialties, higher research degrees, and year of medical
      qualification. RESULTS: Data were analyzed for 315 neurosurgeons (25 female). The
      median h-index and m-quotient were 6.00 and 0.41, respectively. These were
      significantly higher for professors (h-index 21.50; m-quotient 0.71) and for
      those with an additional MD or PhD (11.0; 0.57). There was no significant
      difference in h-index, m-quotient, or higher research degrees between the sexes.
      However, none of the 16 British neurosurgery professors were female.
      Neurosurgeons who specialized in functional/epilepsy surgery ranked highest in
      terms of publication productivity. The 5 top-scoring departments were those in
      Addenbrooke's Hospital, Cambridge; St. George's Hospital, London; Great Ormond
      Street Hospital, London; National Hospital for Neurology and Neurosurgery, Queen
      Square, London; and John Radcliffe Hospital, Oxford. CONCLUSIONS: The h-index is
      a useful bibliometric marker, particularly when comparing between studies and
      individuals. The m-quotient reduces bias toward established researchers. British
      academic neurosurgeons face considerable challenges, and women remain
      underrepresented in both clinical and academic neurosurgery in Britain and
      Ireland.

PMID- 25614944
TI  - Cerebrolysin improves cognitive performance in rats after mild traumatic brain
      injury.
AB  - OBJECT: Long-term memory deficits occur after mild traumatic brain injuries
      (mTBIs), and effective treatment modalities are currently unavailable.
      Cerebrolysin, a peptide preparation mimicking the action of neurotrophic factors,
      has beneficial effects on neurodegenerative diseases and brain injuries. The
      present study investigated the long-term effects of Cerebrolysin treatment on
      cognitive function in rats after mTBI. METHODS: Rats subjected to closed-head
      mTBI were treated with saline (n = 11) or Cerebrolysin (2.5 ml/kg, n = 11)
      starting 24 hours after injury and then daily for 28 days. Sham animals underwent
      surgery without injury (n = 8). To evaluate cognitive function, the modified
      Morris water maze (MWM) test and a social odor-based novelty recognition task
      were performed after mTBI. All rats were killed on Day 90 after mTBI, and brain
      sections were immunostained for histological analyses of amyloid precursor
      protein (APP), astrogliosis, neuroblasts, and neurogenesis. RESULTS: Mild TBI
      caused long-lasting cognitive memory deficits in the MWM and social odor
      recognition tests up to 90 days after injury. Compared with saline treatment,
      Cerebrolysin treatment significantly improved both long-term spatial learning and
      memory in the MWM test and nonspatial recognition memory in the social odor
      recognition task up to 90 days after mTBI (p < 0.05). Cerebrolysin significantly
      increased the number of neuroblasts and promoted neurogenesis in the dentate
      gyrus, and it reduced APP levels and astrogliosis in the corpus callosum, cortex,
      dentate gyrus, CA1, and CA3 regions (p < 0.05). CONCLUSIONS: These results
      indicate that Cerebrolysin treatment of mTBI improves long-term cognitive
      function, and this improvement may be partially related to decreased brain APP
      accumulation and astrogliosis as well as increased neuroblasts and neurogenesis.

PMID- 25614946
TI  - Perineural spread of malignant melanoma from the mandible to the brachial plexus:
      case report.
AB  - Perineural spread is a well-known mechanism of dissemination of head and neck
      malignancies. There are few reports of melanoma involving the brachial plexus in
      the literature. To their knowledge, the authors report the first known case of
      perineural spread of malignant melanoma to the brachial plexus.
      Clinicoradiological and anatomopathological correlation is presented,
      highlighting the importance of peripheral nerve communications in perineural
      spread. 

PMID- 25614945
TI  - Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis:
      initial experience and long-term outcomes.
AB  - OBJECT: The authors assessed the feasibility of intraoperative radiotherapy
      (IORT) using a portable radiation source to treat newly diagnosed, surgically
      resected, solitary brain metastasis (BrM). METHODS: In a nonrandomized
      prospective study, 23 patients with histologically confirmed BrM were treated
      with an Intrabeam device that delivered 14 Gy to a 2-mm depth to the resection
      cavity during surgery. RESULTS: In a 5-year minimum follow-up period, progression
      free survival from the time of surgery with simultaneous IORT averaged (+/- SD)
      22 +/- 33 months (range 1-96 months), with survival from the time of BrM
      treatment with surgery+IORT of 30 +/- 32 months (range 1-96 months) and overall
      survival from the time of first cancer diagnosis of 71 +/- 64 months (range 4-197
      months). For the Graded Prognostic Assessment (GPA), patients with a score of 1.5
      2.0 (n = 12) had an average posttreatment survival of 21 +/- 26 months (range 1
      96 months), those with a score of 2.5-3.0 (n = 7) had an average posttreatment
      survival of 52 +/- 40 months (range 5-94 months), and those with a score of 3.5
      4.0 (n = 4) had an average posttreatment survival of 17 +/- 12 months (range 4-28
      months). A BrM at the treatment site recurred in 7 patients 9 +/- 6 months
      posttreatment, and 5 patients had new but distant BrM 17 +/- 3 months after
      surgery+IORT. Six patients later received whole-brain radiation therapy, 7
      patients received radiosurgery, and 2 patients received both treatments. The
      median Karnofsky Performance Scale scores before and 1 and 3 months after surgery
      were 80, 90, and 90, respectively; at the time of this writing, 3 patients remain
      alive with a CNS progression-free survival of > 90 months without additional BrM
      treatment. CONCLUSIONS: The results of this study demonstrate the feasibility of
      resection combined with IORT at a dose of 14 Gy to a 2-mm peripheral margin to
      treat a solitary BrM. Local control, distant control, and long-term survival were
      comparable to those of other commonly used modalities. Surgery combined with IORT
      seems to be a potential adjunct to patient treatment for CNS involvement by
      systemic cancer.

PMID- 25614947
TI  - Impact of resident involvement in neurosurgery: an analysis of 8748 patients from
      the 2011 American College of Surgeons National Surgical Quality Improvement
      Program database.
AB  - OBJECT: This study evaluates the impact of resident presence in the operating
      room on postoperative outcomes in neurosurgery. METHODS: The authors
      retrospectively reviewed the American College of Surgeons National Surgical
      Quality Improvement Program (ACS-NSQIP) and identified all cases treated in a
      neurosurgery service in 2011. Propensity scoring analysis and multiple logistic
      regression models were used to reduce patient bias and to assess independent
      effect of resident involvement. RESULTS: Of the 8748 neurosurgery cases
      identified, residents were present in 4529 cases. Residents were more likely to
      be involved in complex procedures with longer operative duration. The
      multivariate analysis found that resident involvement was not a statistically
      significant factor for overall complications (OR 1.116, 95% CI 0.961-1.297),
      surgical complications (OR 1.132, 95% CI 0.825-1.554), medical complications (OR
      1.146, 95% CI 0.979-1.343), reoperation (OR 1.250, 95% CI 0.984-1.589), mortality
      (OR 1.164, 95% CI 0.780-1.737), or unplanned readmission (OR 1.148, 95% CI 0.946
      1.393). CONCLUSIONS: In this multicenter study, the authors demonstrated that
      resident involvement in the operating room was not a significant factor for
      postoperative complications in neurosurgery service. This analysis also showed
      that much of the observed difference in postoperative complication rates was
      attributable to other confounding factors. This is a quality indicator for
      resident trainees and current medical education. Maintaining high standards in
      postgraduate training is imperative in enhancing patient care and reducing
      postoperative complications.

PMID- 25614948
TI  - Seizure and anticonvulsant outcomes following stereotactic radiosurgery for
      intracranial arteriovenous malformations.
AB  - OBJECT: Epilepsy associated with arteriovenous malformations (AVMs) has an
      unclear course after stereotactic radiosurgery (SRS). Neither the risks of
      persistent seizures nor the requirement for postoperative antiepileptic drugs
      (AEDs) are well defined. METHODS: The authors performed a retrospective review of
      all patients with AVMs who underwent SRS at the University of Virginia Health
      System from 1989 to 2012. Seizure status was categorized according to a modified
      Engel classification. The effects of demographic, AVM-related, and SRS treatment
      factors on seizure outcomes were evaluated with logistic regression analysis.
      Changes in AED status were evaluated using McNemar's test. RESULTS: Of the AVM
      patients with pre- or post-SRS seizures, 73 with pre-SRS epilepsy had evaluable
      data for subsequent analysis. The median patient age was 37 years (range 5-69
      years), and the median follow-up period was 65.6 months (range 12-221 months).
      Sixty-five patients (89%) achieved seizure remission (Engel Class IA or IB
      outcome). Patients presenting with simple partial or secondarily generalized
      seizures were more likely to achieve Engel Class I outcome (p = 0.045). Twenty
      one (33%) of 63 patients tapered off of pre-SRS AEDs. The incidence of freedom
      from AED therapy increased significantly after SRS (p < 0.001, McNemar's test).
      Of the Engel Class IA patients who continued AED therapy, 54% had patent AVM
      nidi, whereas only 19% continued AED therapy with complete AVM obliteration (p =
      0.05). CONCLUSIONS: Stereotactic radiosurgery is an effective treatment for long
      term AVM-related epilepsy. Seizure-free patients on continued AED therapy were
      more likely to have residual AVM nidi. Simple partial or secondarily generalized
      seizure type were associated with better seizure outcomes following SRS.

PMID- 25614949
TI  - Epigenetic modifications in cutaneous malignant melanoma: EZH2, H3K4me2, and
      H3K27me3 immunohistochemical expression is enhanced at the invasion front of the
      tumor.
AB  - Cancer stem cells and the misregulation of epigenetic modifications have been
      identified to possess a determinative role in carcinogenesis. The purpose of this
      study was to investigate the expression profile of EZH2 and H3K4me2 and H3K27me3,
      which constitute stem cell-like "bivalent" domains, in cutaneous malignant
      melanoma. A comparative analysis of their immunohistochemical expression between
      the invasion front (IF) and the inner tumor mass was also evaluated.
      Immunohistochemical methodology was performed on sections of 89 melanoma lesions
      from 79 patients. The 3 markers studied were identified in the cell nuclei of
      melanoma cells, nevus cells, and normal epidermal keratinocytes. A specific
      distribution pattern of H3K4me2 and H3K27me3 was found, as stronger levels were
      localized at the IF of the tumor (P = 0.034 and P < 0.01, respectively). In
      general, H3K4me2 and H3K27me3 levels were lower in metastatic with respect to
      primary melanoma cases (P = 0.0065 and P = 0.027, respectively). Advanced
      melanoma demonstrated significantly lower H3K4 immunohistochemical expression
      than did cases of lowest Clark level (I) (P = 0.038) or low Breslow depth (<=1
      mm; P < 0.001). Furthermore, EZH2 expression in melanoma cells was higher
      compared with that in nevus cells (P = 0.02). A positive correlation between EZH2
      H3K27me3 (P = 0.03) and H3K4me2-H3K27me3 (P < 0.01) in melanoma cells was also
      found. Our results suggest the possibility that combined immunohistochemical
      expression of EZH2, H3K4me2, and H3K27me3 might identify cancer cells with
      potential stem cell properties, particularly at the IF of this malignancy. This
      hypothesis should be further investigated, as many of the epigenetic changes are
      reversible via pharmacologic manipulations and new therapies, overpassing the
      resistance of advanced melanoma, may be developed.

PMID- 25614950
TI  - Anatomical and ultrasonographic study of the femoral nerve within the iliopsoas
      muscle in beagle dogs and cats.
AB  - OBJECTIVES: An ultrasound (US)-guided ventral suprainguinal approach to block the
      femoral nerve (FN) within the iliopsoas muscle (IPM) has recently been described
      in dogs. The goal of the present study was to provide the operator with
      additional information to locate the FN within the IPM in dogs and cats using US.
      STUDY DESIGN: The study was carried out in three phases: a dissection of the FN
      (phase 1); an in vivo US-assisted nerve study (phase 2), and an anatomical cross
      sectional study (phase 3). ANIMALS: Nine healthy adult beagle dogs and nine
      healthy adult cats. METHODS: Dissections were performed to investigate the
      anatomical characteristics of the FN and its related structures in one dog and
      one cat. Ultrasound scans of the left and right FN were performed in eight dogs
      and eight cats. The FN diameter and the distance between the FN and the external
      iliac artery (EIA) in US images and in anatomical cryosections were measured.
      RESULTS: The median FN diameter did not differ significantly between cats and
      dogs (1.1 mm versus 1.0 mm) or between the two techniques (US versus anatomical
      cross-sectional study) (1.1 mm versus 1.1 mm in dogs; 1.0 mm versus 1.1 mm in
      cats). The US and anatomical measurements of the median distances between the FN
      and EIA differed significantly between dogs and cats (8.2 mm versus 5.8 mm by US;
      5.7 mm versus 4.8 mm in the anatomical study). CONCLUSIONS AND CLINICAL
      RELEVANCE: The distance between the EIA and FN is reproducible in beagle dogs and
      cats and can be used in locating the FN within the IPM.

PMID- 25614951
TI  - Safety and efficacy of diazepam autoinjector for the management of epilepsy.
AB  - Benzodiazepines represent the first choice treatment of acute repetitive
      seizures, and diazepam is one of the main drugs administered to epileptic
      patients in the prehospital setting. Currently, Diazepam rectal gel is the only
      approved therapy for the outpatient management of seizures, but there is a
      growing need for alternative medications for terminating seizures that may be not
      only safe and effective but also socially acceptable. According to this, the
      autoinjector device appears to be a promising tool for the treatment of acute
      repetitive seizures. Recent studies comparing diazepam autoinjector (AI) with
      placebo suggest that diazepam AI could be a safe and effective option to treat
      acute repetitive seizures when administered by trained caregivers in outpatient
      settings. However, additional studies comparing diazepam AI with a standard
      treatment are necessary to define possible added benefits of this technique. 

PMID- 25614952
TI  - Further understanding of cerebral autoregulation at the bedside: possible
      implications for future therapy.
AB  - Cerebral autoregulation reflects the ability of the brain to keep the cerebral
      blood flow (CBF) relatively constant despite changes in cerebral perfusion
      pressure. It is an intrinsic neuroprotective physiological phenomenon often
      suggested as part of pathophysiological pathways in brain research. However,
      despite increasing knowledge of this phenomenon for over 50 years, harnessing
      cerebral autoregulation as a basis for therapy remains an elegant concept rather
      than a practical reality. This raises the question is it useful to measure at the
      bedside or is it merely a scientific curiosity that is too complex and has little
      pragmatic relevance. In this article, we attempt to answer this question by
      demonstrating how cerebral autoregulation assessment can have prognostic value,
      indicate pathological states, and potentially even influence therapy with the use
      of the 'optimal cerebral perfusion pressure' paradigm. Evidence from the
      literature is combined with bedside clinical examples to address the following
      fundamental questions about cerebral autoregulation: What is it? How do we
      measure it? Why is it important? Can we use it as a basis for therapy? 

PMID- 25614953
TI  - Therapy of paraneoplastic disorders of the CNS.
AB  - Paraneoplastic neurological syndromes affecting the CNS are rare, presenting in
      less than 1% of all those with cancer. However, they account for significant
      disability and may respond to treatment. The pathogenesis of paraneoplastic
      neurological syndromes is presumed to relate to loss of self-tolerance spilling
      over from the immune attack on the underlying neoplasm. Testing for anti-neuronal
      antibodies is now available in most tertiary laboratories, enabling targeted
      therapies. While the evidence base for treatment is limited, the response to
      treatment can be largely determined based on the location of the target antigen;
      antibodies against cell surface antigens responding well to treatments targeting
      the humoral response. Intracellular antigen-target syndromes respond less well,
      but may theoretically respond best to T-cell based therapies. In both cases,
      aggressive tumor therapy is indicated. 

PMID- 25614954
TI  - Recent advances in autophagy-based neuroprotection.
AB  - Macroautophagy is a highly regulated intracellular process that, under certain
      circumstances, delivers cytoplasmic components to the lysosomes for degradation.
      It consists of several sequential steps including initiation and nucleation,
      double membrane formation and elongation, formation and maturation of
      autophagosomes and finally autophagosomes/lysosomes fusion and degradation of
      intra-autophagosomal contents by lysosomal enzymes. After decades of considering
      autophagy as a cell death pathway, it has recently been shown to have a survival
      function through clearing of protein aggregates and damaged cytoplasmic
      organelles in response to a variety of stress conditions. Most recently, there is
      increasing evidence from literature revealing that autophagy induction may combat
      neurodegeneration. In the light of this, our current review tried to address the
      recent advances in the role of induced autophagy in neuroprotection with a
      particular focus on its contribution in the most common neurodegenerative
      disorders like Alzheimer's disease, Parkinson's disease and Huntington's disease.

PMID- 25614955
TI  - Characterization of a virulent dog-originated rabies virus affecting more than
      twenty fallow deer (Dama dama) in Inner Mongolia, China.
AB  - Rabies has emerged as a serious problem in the most recent years in northern
      China. A rabies virus (RABV) isolate, IMDRV-13, was recovered from brain samples
      of dog-bitten rabid fallow deer (Dama dama) in a farm in Hohhot, Inner Mongolia.
      We tested the susceptibility of mouse neuroblastoma (MNA) cells and BSR cells as
      well as that of adult mice to IMDRV-13. The isolate was found to be a virulent
      isolate with an equivalent pathogenicity index (0.12) and a slight lower
      neurotropism index (1.07) compared with those of challenge virus standard, CVS
      24, which was 0.13 and 1.23, respectively. The complete genome of IMDRV-13 was
      determined subsequently and found to be 11,924 nucleotides (nt) in length with
      the same genomic organization as other RABVs. Phylogenetic tree based on complete
      genome sequences of 43 RABV isolates and strains indicated that IMDRV-13, along
      with other two isolates in Inner Mongolia, CNM1101C and CNM1104D, clustered
      within the dog-associated China I clade, which is also the dominant lineage in
      the current rabies epidemic in China. In addition, sequence analysis of the
      glycoprotein G identified an amino acid substitution (I338->T338) unique to the
      IMDRV-13 within antigenic sites III (330-338), this mutation also leads to an
      additional potential N-glycosylation site (N336), which may represent a useful
      model to study relationship of N-glycosylation in G protein and specific
      properties such as pathogenicity or host adaption of RABV. 

PMID- 25614956
TI  - Missing elements in the Institute of Medicine Report on graduate medical
      education.

PMID- 25614957
TI  - Polyarticular Gout Flare Masquerading as Sepsis.

PMID- 25614958
TI  - Organizing polarized delivery of exosomes at synapses.
AB  - Exosomes are extracellular vesicles that transport different molecules between
      cells. They are formed and stored inside multivesicular bodies (MVB) until they
      are released to the extracellular environment. MVB fuse along the plasma
      membrane, driving non-polarized secretion of exosomes. However, polarized
      signaling potentially directs MVBs to a specific point in the plasma membrane to
      mediate a focal delivery of exosomes. MVB polarization occurs across a broad set
      of cellular situations, e.g. in immune and neuronal synapses, cell migration and
      in epithelial sheets. In this review, we summarize the current state of the art
      of polarized MVB docking and the specification of secretory sites at the plasma
      membrane. The current view is that MVB positioning and subsequent exosome
      delivery requires a polarizing, cytoskeletal dependent-trafficking mechanism. In
      this context, we propose scenarios in which biochemical and mechanical signals
      could drive the polarized delivery of exosomes in highly polarized cells, such as
      lymphocytes, neurons and epithelia. 

PMID- 25614959
TI  - Group A Streptococcal meningitis in adults.
AB  - OBJECTIVES: We report on the incidence, clinical characteristics, and bacterial
      genotype of group A streptococcal (GAS) meningitis in the Netherlands. METHODS:
      We assessed the incidence, clinical characteristics, and outcome of patients with
      GAS meningitis from a nationwide cohort study of adults with community-acquired
      bacterial meningitis in the Netherlands from 2006 to 2013. RESULTS: GAS was
      identified in 26 of 1322 patients with community-acquired bacterial meningitis
      (2%); 9 cases (35%) occurred in the first four months of 2013. GAS meningitis was
      often preceded by otitis or sinusitis (24 of 26 [92%]) and a high proportion of
      patients developed complications during clinical course (19 of 26 [73%]).
      Subdural empyema occurred in 8 of 26 patients (35%). Nine patients underwent
      mastoidectomy and in 5 patients neurosurgical evacuation of the subdural empyema
      was performed. Five of 26 patients (19%) died and 11 of 21 surviving patient had
      neurologic sequelae (52%). Infection with the emm1 and cc28 GAS genotype was
      associated with subdural empyema (both 4 of 6 [67%] vs. 2 of 14 [14%]; P =
      0.037). CONCLUSIONS: GAS meningitis is an uncommon but severe disease. Patients
      are at risk for empyema, which is associated with infection with the emm1 and
      cc28 genotype.

PMID- 25614960
TI  - Reduction in rotavirus disease due to the infant immunisation programme in
      England; evidence from national surveillance.

PMID- 25614961
TI  - Response to 'reduced prescribing of benzodiazepines in denmark and norway'.

PMID- 25614962
TI  - All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with
      hepatitis C virus genotype 3 infection: ALLY-3 phase III study.
AB  - Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection
      are limited, with the currently approved all-oral regimens requiring 24-week
      treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3;
      ClinicalTrials.gov: NCT02032901) evaluated the 12-week regimen of daclatasvir
      (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF;
      pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were
      either treatment naive (n = 101) or treatment experienced (n = 51) and received
      DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the
      proportions of treatment-naive and treatment-experienced patients achieving a
      sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12
      rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naive and treatment
      experienced patients, respectively; no virological breakthrough was observed, and
      >=99% of patients had a virological response (VR) at the end of treatment. SVR12
      rates were higher in patients without cirrhosis (96%; 105 of 109) than in those
      with cirrhosis (63%; 20 of 32). Five of seven patients who previously failed
      treatment with an SOF-containing regimen and 2 of 2 who previously failed
      treatment with an alisporivir-containing regimen achieved SVR12. Baseline
      characteristics, including gender, age, HCV-RNA levels, and interleukin-28B
      genotype, did not impact virological outcome. DCV plus SOF was well tolerated;
      there were no adverse events (AEs) leading to discontinuation and only 1 serious
      AE on-treatment, which was unrelated to study medications. The few treatment
      emergent grade 3/4 laboratory abnormalities that were observed were transient.
      CONCLUSION: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of patients
      with genotype 3 infection without cirrhosis and was well tolerated. Additional
      evaluation to optimize efficacy in genotype 3-infected patients with cirrhosis is
      underway.

PMID- 25614963
TI  - Transition-metal-catalyzed arylation of nitroimidazoles and further
      transformations of manipulable nitro group.
AB  - Pd- or Ni-catalyzed C-H arylation of 4-nitroimidazole derivatives directed by a
      manipulable nitro group was developed. The reaction tolerates a wide range of
      substituted aryl halides and 4-nitroimidazoles. The experiments indicated that
      the nitro group has influence on regioselectivity of the reaction. In addition,
      we have shown that the efficiency of the Suzuki-Miyaura cross-coupling reaction
      of nitroimidazoles is slightly lower in comparison to the direct C-H arylation.
      The exploration of the chemical potential of the nitro group and a putative
      reaction mechanism are discussed. 

PMID- 25614964
TI  - Pheromones affecting ovary activation and ovariole loss in the Asian honey bee
      Apis cerana.
AB  - The Asian hive bee Apis cerana has similar queen mandibular pheromones (QMP) to
      the Western honey bee Apismellifera. However the effects of individual QMP
      components have never been tested to determine their effects on the reproductive
      physiology of A. cerana workers. We fed one queen equivalent of each of the major
      components of A. cerana QMP to groups of c.a. 500 day-old, caged, workers twice a
      day until the workers were 10 days old. Half of the cages were also provided with
      10% royal jelly in the food. Workers were sampled each day and dissected to
      determine the number of ovarioles and the degree of ovary activation (egg
      development). In cages treated with 9-carbon fatty acids ovary activation was
      minimal, whereas the 10-carbon acids suppressed ovary activation very little.
      Royal jelly enhanced ovary activation, especially in cages treated with 10-carbon
      acids. The number of ovarioles declined with bee age, but the rate of decline was
      slowed by the 9-carbon acids in particular. The results show conservation of the
      composition and function of QMP between A. cerana and A. mellifera and support
      the hypothesis that QMP is an honest signal of queen fecundity rather than a
      chemical castrator of workers.

PMID- 25614965
TI  - Antioxidant responses of Propylaea japonica (Coleoptera: Coccinellidae) exposed
      to high temperature stress.
AB  - Temperature is one of the most important environmental factors, and is
      responsible for a variety of physiological stress responses in organisms. Induced
      thermal stress is associated with elevated reactive oxygen species (ROS)
      generation leading to oxidative damage. The ladybeetle, Propylaea japonica
      (Thunberg) (Coleoptera: Coccinellidae), is considered a successful natural enemy
      because of its tolerance to high temperatures in arid and semi-arid areas in
      China. In this study, we investigated the effect of high temperatures (35, 37,
      39, 41 and 43  degrees C) on the survival and activities of antioxidant enzymes,
      including superoxide dismutase (SOD), catalase (CAT), peroxidases (POD),
      glutathione-S-transferases (GST), and total antioxidant capacity (TAC) as well as
      malondialdehyde (MDA) concentrations in P. japonica adults. The results indicated
      that P. japonica adults could not survive at 43  degrees C. CAT, GST and TAC were
      significantly increased when compared to the control (25  degrees C), and this
      played an important role in the process of antioxidant response to thermal
      stress. SOD and POD activity, as well as MDA, did not differ significantly at 35
      and 37  degrees C compared to the control; however, there were increased levels
      of SOD, POD and MDA when the temperature was above 37  degrees C. These results
      suggest that thermal stress leads to oxidative stress and antioxidant enzymes
      play important roles in reducing oxidative damage in P. japonica adults. This
      study represents the first comprehensive report on the antioxidant defense system
      in predaceous coccinellids (the third trophic level). The findings provide useful
      information for predicting population dynamics and understanding the potential
      for P. japonica as a natural enemy to control pest insects under varied
      environmental conditions.

PMID- 25614967
TI  - Preparation and characterization of novel IgG affinity resin coupling anti-Fc
      camelid single-domain antibodies.
AB  - This work aimed to evaluate novel affinity resin used to purify immunoglobulin G
      (IgG) with a variable domain of the heavy chain of the heavy-chain antibody (VHH)
      as an affinity ligand. The VHH, isolated from a naive camelid single-domain phage
      display library, exhibits not only affinity to the fragment crystallizable (Fc)
      region of IgG but also high thermal stability. This anti-Fc VHH (AFV) was
      expressed as a soluble protein in Escherichia coli and purified using a simple
      heat treatment procedure. The effects of pH and NaCl concentrations on the
      capacity of AFV resin were also investigated. Results showed a robust property of
      the AFV resin. It could bind IgGs at various pH conditions (from 6.0 to 9.0) and
      NaCl concentrations. The static binding capacities of AFV resin ranged from
      3.40+/-0.53mg/ml to 15.04+/-0.37mg/ml measured using rabbit, mouse, and human
      IgGs. The bound IgGs can be efficiently eluted at pH 5.0, which is conducive to
      acid-sensitive IgGs and prevents the aggregation of IgGs. After 10 purification
      cycles or a 7-day period of storage at 37 degrees C, recovery did not decrease.
      These findings suggested that VHHs from non-immunized library could also be
      robust and functional reagent as an affinity purification ligand. 

PMID- 25614966
TI  - An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell
      dysfunction.
AB  - The inhibitory receptor T-cell immunoglobulin and mucin domain-3 (Tim-3) has
      emerged as a critical regulator of the T-cell dysfunction that develops in
      chronic viral infections and cancers. However, little is known regarding the
      signalling pathways that drive Tim-3 expression. Here, we demonstrate that
      interleukin (IL)-27 induces nuclear factor, interleukin 3 regulated (NFIL3),
      which promotes permissive chromatin remodelling of the Tim-3 locus and induces
      Tim-3 expression together with the immunosuppressive cytokine IL-10. We further
      show that the IL-27/NFIL3 signalling axis is crucial for the induction of Tim-3
      in vivo. IL-27-conditioned T helper 1 cells exhibit reduced effector function and
      are poor mediators of intestinal inflammation. This inhibitory effect is NFIL3
      dependent. In contrast, tumour-infiltrating lymphocytes from IL-27R(-/-) mice
      exhibit reduced NFIL3, less Tim-3 expression and failure to develop dysfunctional
      phenotype, resulting in better tumour growth control. Thus, our data identify an
      IL-27/NFIL3 signalling axis as a key regulator of effector T-cell responses via
      induction of Tim-3, IL-10 and T-cell dysfunction. 

PMID- 25614968
TI  - Rapid preparation of molecularly imprinted polymers by microwave-assisted
      emulsion polymerization for the extraction of florfenicol in milk.
AB  - In this study, we proposed a rapid and simple method for the preparation of
      molecularly imprinted polymers (MIPs) by emulsion polymerization. The
      polymerization process was accelerated by microwave heating, and the reaction
      time was greatly shortened. The obtained MIPs were spherical in shape and
      exhibited a uniform morphology. The MIPs with selectivity and high affinity to
      florfenicol were successfully applied as solid-phase extraction materials to
      extract and clean up the florfenicol in milk, followed by liquid chromatography
      tandem mass spectrometry (LC-MS) analysis. The parameters affecting the
      performance of extraction and LC-MS analysis were evaluated. The detection limit
      of the method was 4.1ngmL(-1). The relative standard deviations of intra- and
      inter-day were in the range of 3.5-4.7% and 3.9-7.5%, respectively. 

PMID- 25614971
TI  - High glucose upregulates CYP24A1 expression which attenuates the ability of
      1,25(OH)2D3 to increase NGF secretion in a rat Schwann cell line RSC96.
AB  - Vitamin D deficiency or insufficiency is an independent risk factor for diabetic
      peripheral neuropathy (DPN), but the relationship between 1,25(OH)2D3 and DPN
      remains unknown. We found that 1,25(OH)2D3 stimulated the secretion of nerve
      growth factor (NGF) in rat Schwann cell line RSC96, but ability of 1,25(OH)2D3 to
      increase NGF protein was impaired under high glucose conditions. High glucose
      upregulated the expression of CYP24A1 protein, which catalyzes the conversion of
      1,25(OH)2D3 into inactive products, further impairing the ability of 1,25(OH)2D3
      to upregulate NGF secretion in Schwann cells. Inhibition of CYP24A1 protein
      expression ameliorated the secretion of NGF in response to 1,25(OH)2D3. The
      findings of this study suggest that CYP24A1 protein plays an important role in
      the relationship between DPN and 1,25(OH)2D3. 

PMID- 25614969
TI  - Metabolites identification of glycyrin and glycyrol, bioactive coumarins from
      licorice.
AB  - Coumarins are an important group of bioactive constituents in licorice
      (Glycyrrhiza uralensis), a worldwide popular herbal medicine. This study aims to
      elucidate the metabolism of two major licorice coumarins, glycyrin and glycyrol
      in rats. After oral administration of 40mg/kg glycyrin, neither the parent
      compound nor its metabolites could be detected in rats plasma or urine samples,
      indicating that glycyrin had poor oral bioavailability. Two hydroxylated
      metabolites, 4"-hydroxyl glycyrin and 5"-hydroxyl glycyrin, were detected in rat
      liver microsome incubation system. Among them, the major metabolite 4"-hydroxyl
      glycyrin, which is a new compound, was obtained by microbial transformation of
      Syncephalastrum racemosum AS 3.264. Its structure was fully identified by 1D and
      2D NMR. Meanwhile, glycyrol, together with three metabolites, were detected in
      rats urine and fecal samples after oral administration (40mg/kg). Their
      structures were tentatively characterized by LC/MS. Glycyrol mainly undertakes
      hydroxylation metabolism, accompanied by hydration and dehydrogenation as minor
      reactions. This is the first systematic study on metabolism of glycyrin and
      glycyrol. The results could be valuable to evaluate druggability of these
      bioactive natural products. 

PMID- 25614972
TI  - Factors related to psychotherapists' self-assessment when treating anxiety and
      other disorders.
AB  - The aim of the study was to replicate and extend recent findings regarding
      therapists' self-assessment biases. This study examined clinicians' estimates of
      their abilities when working with general clinical groups and with anxious
      patients, and of the recovery/improvement rates of their clients. It also
      considered what clinician personality traits and clinical practice elements were
      associated with such estimates. A total of 195 out 801 clinicians completed a
      survey regarding self-ratings, team ratings, therapy outcomes for their clients,
      and their own personality traits. The great majority of clinicians rated
      themselves and their teams as being better clinicians than their peers, though
      not to as extreme a level as in the previous study. They also reported
      exceptionally positive therapy outcomes. Due to the large proportion of non
      responders, it is possible that these findings do not reflect actual self
      assessment bias, but a greater willingness to participate among clinicians who
      are more skilled and with particular personality styles. However, the data
      suggest that perceptions of skill and therapy outcome might be associated with
      clinician personality characteristics, though not with other clinical practice
      variables. These interpretations should be treated with caution due to the
      limited response rate. Different possible explanations for these patterns of self
      assessment are outlined, including conscious and unconscious processes. Methods
      for enhancing accurate skill perception are discussed, including self-monitoring
      and supervision. 

PMID- 25614973
TI  - Cortical structural abnormalities in very preterm children at 7 years of age.
AB  - We analyzed long-lasting alterations in brain morphometry associated with preterm
      birth using volumetric and surface-based analyses applied to children at age 7
      years. Comparison of 24 children born very preterm (VPT) to 24 healthy term-born
      children revealed reductions in total cortical gray matter volume, white matter
      volume, cortical surface area and gyrification index. Regional cortical shape
      abnormalities in VPT children included the following: shallower anterior superior
      temporal sulci, smaller relative surface area in the inferior sensori-motor
      cortex and posterior superior temporal cortex, larger relative surface area and a
      cingulate sulcus that was shorter or more interrupted in medial frontoparietal
      cortex. These findings indicate a complex pattern of regional vulnerabilities in
      brain development that may contribute to the diverse and long-lasting
      neurobehavioral consequences that can occur after very premature birth.

PMID- 25614976
TI  - Design optimization of a radial functionally graded dental implant.
AB  - In this work, we use FEA to test the hypothesis that a low-modulus coating of a
      cylindrical zirconia dental implant would reduce the stresses in the peri-implant
      bone and we use design optimization and the rule of mixture to estimate the
      elastic modulus and the porosity of the coating that provides optimal stress
      shielding. We show that a low-modulus coating of a dental implant significantly
      reduces the maximum stresses in the peri-implant bone without affecting the
      average stresses thus creating a potentially favorable biomechanical environment.
      Our results suggest that a resilient coating is capable of reducing the maximum
      compressive and tensile stresses in the peri-implant bone by up to 50% and the
      average stresses in the peri-implant bone by up to 15%. We further show that a
      transitional gradient between the high-modulus core and the low-modulus coating
      is not necessary and for a considered zirconia/HA composite the optimal thickness
      of the coating is 100 u with its optimal elastic at the lowest value considered
      of 45 GPa.

PMID- 25614975
TI  - Oligomeric complexes of some heteroaromatic ligands and aromatic diamines with
      rhodium and molybdenum tetracarboxylates: 13C and 15N CPMAS NMR and density
      functional theory studies.
AB  - Seven new oligomeric complexes of 4,4'-bipyridine; 3,3'-bipyridine; benzene-1,4
      diamine; benzene-1,3-diamine; benzene-1,2-diamine; and benzidine with rhodium
      tetraacetate, as well as 4,4'-bipyridine with molybdenum tetraacetate, have been
      obtained and investigated by elemental analysis and solid-state nuclear magnetic
      resonance spectroscopy, (13)C and (15)N CPMAS NMR. The known complexes of
      pyrazine with rhodium tetrabenzoate, benzoquinone with rhodium tetrapivalate,
      4,4'-bipyridine with molybdenum tetrakistrifluoroacetate and the 1 : 1 complex of
      2,2'-bipyridine with rhodium tetraacetate exhibiting axial-equatorial ligation
      mode have been obtained as well for comparison purposes. Elemental analysis
      revealed 1 : 1 complex stoichiometry of all complexes. The (15)N CPMAS NMR
      spectra of all new complexes consist of one narrow signal, indicating regular
      uniform structures. Benzidine forms a heterogeneous material, probably containing
      linear oligomers and products of further reactions. The complexes were
      characterized by the parameter complexation shift Deltadelta (Deltadelta =
      deltacomplex  - deltaligand). This parameter ranged from around -40 to -90 ppm in
      the case of heteroaromatic ligands, from around -12 to -22 ppm for diamines and
      from -16 to -31 ppm for the complexes of molybdenum tetracarboxylates with 4,4'
      bipyridine. The experimental results have been supported by a density functional
      theory computation of (15)N NMR chemical shifts and complexation shifts at the
      non-relativistic Becke, three-parameter, Perdew-Wang 91/[6-311++G(2d,p),
      Stuttgart] and GGA-PBE/QZ4P levels of theory and at the relativistic scalar and
      spin-orbit zeroth order regular approximation/GGA-PBE/QZ4P level of theory.
      Nucleus-independent chemical shifts have been calculated for the selected
      compounds.

PMID- 25614974
TI  - Pre-stimulus functional networks modulate task performance in time-pressured
      evidence gathering and decision-making.
AB  - Rapid perceptual decision-making is believed to depend upon efficient allocation
      of neural resources to the processing of transient stimuli within task-relevant
      contexts. Given decision-making under severe time pressure, it is reasonable to
      posit that the brain configures itself, prior to processing stimulus information,
      in a way that depends upon prior beliefs and/or anticipation. However, relatively
      little is known about such configuration processes, how they might be manifested
      in the human brain, or ultimately how they mediate task performance. Here we show
      that network configuration, defined via pre-stimulus functional connectivity
      measures estimated from functional magnetic resonance imaging (fMRI) data, is
      predictive of performance in a time-pressured Go/No-Go task. Specifically, using
      connectivity measures to summarize network properties, we show that pre-stimulus
      brain state can be used to discriminate behaviorally correct and incorrect
      trials, as well as behaviorally correct commission and omission trial categories.
      More broadly, our results show that pre-stimulus functional configurations of
      cortical and sub-cortical networks can be a major determiner of task performance.

PMID- 25614977
TI  - Impact of polyphenolic components from mulberry on apoptosis of vascular smooth
      muscle cells.
AB  - BACKGROUND: Previous studies have shown that mulberry polyphenolic compounds have
      an anti-atherosclerotic effect in rabbits. Apoptosis of vascular smooth muscle
      cells (VSMCs) is the key determinant of the number of VSMCs in remodeling. To
      examine the effect of mulberry polyphenol extracts (MPEs) on the apoptosis of
      VSMCs and thus the prevention of atherosclerosis, this study investigated the
      ability of MPEs to induce apoptosis in vitro and the underlying mechanism.
      RESULTS: It was found that MPEs initially activated JNK/p38 and p53, which in
      turn activated both Fas-ligand and mitochondrial pathways, thereby causing
      mitochondrial translocation of Bax and a reduction in Bcl-2. This then triggered
      the cleavage of procaspases, finally resulting in apoptosis of VSMCs. CONCLUSION:
      This study shows that MPEs may suppress atherosclerosis through stimulating
      apoptosis of VSMCs via activating JNK/p38 and p53 signaling.

PMID- 25614978
TI  - Evaluating language environment analysis system performance for Chinese: a pilot
      study in Shanghai.
AB  - PURPOSE: The purpose of this study was to evaluate performance of the Language
      Environment Analysis (LENA) automated language-analysis system for the Chinese
      Shanghai dialect and Mandarin (SDM) languages. METHOD: Volunteer parents of 22
      children aged 3-23 months were recruited in Shanghai. Families provided daylong
      in-home audio recordings using LENA. A native speaker listened to 15 min of
      randomly selected audio samples per family to label speaker regions and provide
      Chinese character and SDM word counts for adult speakers. LENA segment labeling
      and counts were compared with rater-based values. RESULTS: LENA demonstrated good
      sensitivity in identifying adult and child; this sensitivity was comparable to
      that of American English validation samples. Precision was strong for adults but
      less so for children. LENA adult word count correlated strongly with both Chinese
      characters and SDM word counts. LENA conversational turn counts correlated
      similarly with rater-based counts after the exclusion of three unusual samples.
      Performance related to some degree to child age. CONCLUSIONS: LENA adult word
      count and conversational turn provided reasonably accurate estimates for SDM over
      the age range tested. Theoretical and practical considerations regarding LENA
      performance in non-English languages are discussed. Despite the pilot nature and
      other limitations of the study, results are promising for broader cross
      linguistic applications.

PMID- 25614979
TI  - Multispectral imaging of absorption and scattering properties of in vivo exposed
      rat brain using a digital red-green-blue camera.
AB  - In order to estimate multispectral images of the absorption and scattering
      properties in the cerebral cortex of in vivo rat brain, we investigated spectral
      reflectance images estimated by the Wiener estimation method using a digital RGB
      camera. A Monte Carlo simulation-based multiple regression analysis for the
      corresponding spectral absorbance images at nine wavelengths (500, 520, 540, 560,
      570, 580, 600, 730, and 760 nm) was then used to specify the absorption and
      scattering parameters of brain tissue. In this analysis, the concentrations of
      oxygenated hemoglobin and that of deoxygenated hemoglobin were estimated as the
      absorption parameters, whereas the coefficient a and the exponent b of the
      reduced scattering coefficient spectrum approximated by a power law function were
      estimated as the scattering parameters. The spectra of absorption and reduced
      scattering coefficients were reconstructed from the absorption and scattering
      parameters, and the spectral images of absorption and reduced scattering
      coefficients were then estimated. In order to confirm the feasibility of this
      method, we performed in vivo experiments on exposed rat brain. The estimated
      images of the absorption coefficients were dominated by the spectral
      characteristics of hemoglobin. The estimated spectral images of the reduced
      scattering coefficients had a broad scattering spectrum, exhibiting a larger
      magnitude at shorter wavelengths, corresponding to the typical spectrum of brain
      tissue published in the literature. The changes in the estimated absorption and
      scattering parameters during normoxia, hyperoxia, and anoxia indicate the
      potential applicability of the method by which to evaluate the pathophysiological
      conditions of in vivo brain due to the loss of tissue viability.

PMID- 25614980
TI  - Semantic retrieval over time in the aging brain: Structural evidence of
      hippocampal contribution.
AB  - This study investigates relationship between regional cerebral volumes and
      performances over time of a categorical fluency task, in a sample of older adults
      (n = 316). Using voxel-wise technique, the relationship between local grey matter
      volume and Isaacs Set Test (IST) scores at its early (first 15 sec) and late
      (last 15 sec) phase production was analyzed with a linear regression model
      adjusting for age, sex, educational level, ApoEE4 allele, handedness and Grey
      Matter atrophy. Lower early IST scores were associated with smaller volumes in
      bilateral inferior frontal gyri and in right thalamus, whereas lower late IST
      scores were associated to smaller left inferior parietal gyrus and left anterior
      hippocampus. An analysis based on automatic segmentation of hippocampus confirmed
      the latest relationship which cannot be attributed to the correlation of each
      variable with global cognitive impairment because it remained when MMSE was
      accounted for. We observed a switch from frontal to temporo-parietal regions as
      words retrieval become more difficult over time. Automatic speech production of
      the early phase of the category fluency task is dependent on executive networks
      integrity whereas controlled speech production of the late phase is dependent on
      memory networks integrity, including left hippocampus. These results are
      concordant with recent imaging studies expanding the implication of hippocampus
      to semantic memory performances and they underlie the need to consider verbal
      fluency task over time.

PMID- 25614981
TI  - Copper homeostasis in Mycobacterium tuberculosis.
AB  - Copper (Cu) is a trace element essential for the growth and development of almost
      all organisms, including bacteria. However, Cu overload in most systems is toxic.
      Studies show Cu accumulates in macrophage phagosomes infected with bacteria,
      suggesting Cu provides an innate immune mechanism to combat invading pathogens.
      To counteract the host-supplied Cu, increasing evidence suggests that bacteria
      have evolved Cu resistance mechanisms to facilitate their pathogenesis. In
      particular, Mycobacterium tuberculosis (Mtb), the causative agent of
      tuberculosis, has evolved multiple pathways to respond to Cu. Here, we summarize
      what is currently known about Cu homeostasis in Mtb and discuss potential sources
      of Cu encountered by this and other pathogens in a mammalian host. 

PMID- 25614982
TI  - Data mining strategies to improve multiplex microbead immunoassay tolerance in a
      mouse model of infectious diseases.
AB  - Multiplex methodologies, especially those with high-throughput capabilities
      generate large volumes of data. Accumulation of such data (e.g., genomics,
      proteomics, metabolomics etc.) is fast becoming more common and thus requires the
      development and implementation of effective data mining strategies designed for
      biological and clinical applications. Multiplex microbead immunoassay (MMIA), on
      xMAP or MagPix platform (Luminex), which is amenable to automation, offers a
      major advantage over conventional methods such as Western blot or ELISA, for
      increasing the efficiencies in serodiagnosis of infectious diseases. MMIA allows
      detection of antibodies and/or antigens efficiently for a wide range of
      infectious agents simultaneously in host blood samples, in one reaction vessel.
      In the process, MMIA generates large volumes of data. In this report we
      demonstrate the application of data mining tools on how the inherent large volume
      data can improve the assay tolerance (measured in terms of sensitivity and
      specificity) by analysis of experimental data accumulated over a span of two
      years. The combination of prior knowledge with machine learning tools provides an
      efficient approach to improve the diagnostic power of the assay in a continuous
      basis. Furthermore, this study provides an in-depth knowledge base to study
      pathological trends of infectious agents in mouse colonies on a multivariate
      scale. Data mining techniques using serodetection of infections in mice,
      developed in this study, can be used as a general model for more complex
      applications in epidemiology and clinical translational research. 

PMID- 25614983
TI  - A low-dose beta1-blocker in combination with milrinone improves intracellular
      Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced
      diastolic Ca2+ leakage from the sarcoplasmic reticulum.
AB  - OBJECTIVES: The purpose of this study was to investigate whether adding a low
      dose beta1-blocker to milrinone improves cardiac function in failing
      cardiomyocytes and the underlying cardioprotective mechanism. BACKGROUND: The
      molecular mechanism underlying how the combination of low-dose beta1-blocker and
      milrinone affects intracellular Ca(2+) handling in heart failure remains unclear.
      METHODS: We investigated the effect of milrinone plus landiolol on intracellular
      Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+)
      sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in
      normal and failing canine cardiomyocytes and used immunoblotting to determine the
      phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB).
      RESULTS: In failing cardiomyocytes, CaSF significantly increased, and peak CaT
      and CS markedly decreased compared with normal myocytes. Administration of
      milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased
      with a slight increase in {Ca(2+)}SR. Co-administration of beta1-blocker
      landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte
      function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and
      peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the
      hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no
      effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol
      significantly inhibited the alternans of CaT and CS under a fixed pacing rate
      (0.5 Hz) in failing cardiomyocytes. CONCLUSION: A low-dose beta1-blocker in
      combination with milrinone improved cardiac function in failing cardiomyocytes,
      apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent
      diastolic Ca(2+) leak.

PMID- 25614984
TI  - Reduced flexibility associated with metabolic syndrome in community-dwelling
      elders.
AB  - BACKGROUND: The ageing process may lead to reductions in physical fitness, a
      known risk factor in the development of metabolic syndrome. The purpose of the
      current study was to evaluate cross-sectional and combined associations of
      metabolic syndrome with body composition and physical fitness in a community
      based geriatric population. METHODS: A total of 628 community-dwelling elders
      attending a geriatric health examination were enrolled in the study. The
      diagnosis of metabolic syndrome was based on the modified National Cholesterol
      Education Program Adult Treatment Panel III (NCEP ATP III) criterion with Asian
      cutoff of waist girth was adopted in this study. Body composition was obtained
      using bioimpedance analysis, and physical fitness was evaluated through the
      measurement of muscle strength (handgrip force), lower extremity muscle endurance
      (sit-to-stand test), flexibility (sit-and-reach test), and cardiorespiratory
      endurance (2-minute step test). Multivariable logistic regression and correlation
      analysis were performed to determine the association of metabolic syndrome with
      body composition and functionality variables. RESULTS: Metabolic syndrome was
      associated with increased skeletal muscle index (SMI) (odds ratio (OR), 1.61, 95%
      confidence interval (CI), 1.25-2.07) and decreased flexibility (OR, 0.97, 95% CI,
      0.95-0.99) compared with those without metabolic syndrome. When body mass index
      was accounted for in the analysis, the association of SMI with metabolic syndrome
      was reduced. Waist circumference was positively correlated with SMI but
      negatively correlated with flexibility, whereas high density lipoprotein was
      positively correlated with flexibility but negatively correlated with SMI.
      CONCLUSION: Reduced flexibility was positively associated with metabolic syndrome
      independent of age, gender, body composition, and functionality measurements in a
      community based geriatric population. Significant associations between metabolic
      syndrome with muscle strength and cardiorespiratory fitness in the elderly were
      not observed. Furthermore, flexibility should be included in the complete
      evaluation for metabolic syndrome.

PMID- 25614985
TI  - Low serum high density lipoprotein cholesterol concentration is an independent
      predictor for enhanced inflammation and endothelial activation.
AB  - BACKGROUND: Inflammation, endothelial activation and oxidative stress have been
      established as key events in the initiation and progression of atherosclerosis.
      High-density lipoprotein cholesterol (HDL-c) is protective against
      atherosclerosis and coronary heart disease, but its association with
      inflammation, endothelial activation and oxidative stress is not well
      established. OBJECTIVES: (1) To compare the concentrations of biomarkers of
      inflammation, endothelial activation and oxidative stress in subjects with low
      HDL-c compared to normal HDL-c; (2) To examine the association and correlation
      between HDL-c and these biomarkers and (3) To determine whether HDL-c is an
      independent predictor of these biomarkers. METHODS: 422 subjects (mean age+/-SD =
      43.2+/-11.9 years) of whom 207 had low HDL-c concentrations (HDL-c <1.0 mmol/L
      and <1.3 mmol/L for males and females respectively) and 215 normal controls (HDL
      c >=1.0 and >=1.3 mmol/L for males and females respectively) were recruited in
      this study. The groups were matched for age, gender, ethnicity, smoking status,
      diabetes mellitus and hypertension. Fasting blood samples were collected for
      analysis of biomarkers of inflammation [high-sensitivity C-reactive protein
      (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell
      Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM
      1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density
      Lipoprotein (ox-LDL) and Malondialdehyde (MDA)]. RESULTS: Subjects with low HDL-c
      had greater concentrations of inflammation, endothelial activation and oxidative
      stress biomarkers compared to controls. There were negative correlations between
      HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial
      activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and
      oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively).
      Multiple linear regression analysis showed HDL-c as an independent predictor of
      IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding
      factors. CONCLUSION: Low serum HDL-c concentration is strongly correlated with
      enhanced status of inflammation, endothelial activation and oxidative stress. It
      is also an independent predictor for enhanced inflammation and endothelial
      activation, which are pivotal in the pathogenesis of atherosclerosis and
      atherosclerosis-related complications.

PMID- 25614986
TI  - Cognitive functioning in clinically stable patients with bipolar disorder I and
      II.
AB  - OBJECTIVES: Bipolar disorder is accompanied by cognitive impairments, which
      persists during euthymic phases. The purpose of the present study was to identify
      those neuropsychological tests that most reliably tell euthymic bipolar patients
      and controls apart, and to clarify the extent to which these cognitive
      impairments are clinically significant as judged from neuropsychological norms.
      METHODS: Patients with bipolar disorder (type I: n = 64; type II: n = 44) and
      controls (n = 86) were examined with a comprehensive neuropsychological test
      battery yielding 47 measures of executive functioning, speed, memory, and verbal
      skills. Multivariate analysis was used to build a model of cognitive performance
      with the ability to expose underlying trends in data and to reveal cognitive
      differences between patients and controls. RESULTS: Patients with bipolar
      disorder and controls were partially separated by one predictive component of
      cognitive performance. Additionally, the relative relevance of each cognitive
      measure for such separation was decided. Cognitive tests measuring set shifting,
      inhibition, fluency, and searching (e.g., Trail Making Test, Color-Word) had
      strongest discriminating ability and most reliably detected cognitive impairments
      in the patient group. CONCLUSIONS: Both bipolar disorder type I and type II were
      associated with cognitive impairment that for a sizeable minority is significant
      in a clinical neuropsychological sense. We demonstrate a combination of
      neuropsychological tests that reliably detect cognitive impairment in bipolar
      disorder.

PMID- 25614989
TI  - Fertility preservation in cancer survivors.
AB  - Due to the increasing number of long-term cancer survivors, physicians of all
      specialties are confronted with the need to prevent side effects of the applied
      oncologic treatments. In the field of reproductive medicine fertility
      preservation has gained importance as most oncologic treatments have detrimental
      immediate or long-term impacts on male and female fertility. The American Society
      of Clinical Oncology and the American Society for Reproductive Medicine, as well
      as the recently founded International Society for Fertility Preservation propose
      several established and investigational options for fertility preservation. This
      review aims to summarize currently available techniques for fertility
      preservation and future perspectives in this field, as well as to provide
      recommendations for patient follow-up after cancer and during pregnancy. 

PMID- 25614987
TI  - Carotenoid content and root color of cultivated carrot: a candidate-gene
      association study using an original broad unstructured population.
AB  - Accumulated in large amounts in carrot, carotenoids are an important product
      quality attribute and therefore a major breeding trait. However, the knowledge of
      carotenoid accumulation genetic control in this root vegetable is still limited.
      In order to identify the genetic variants linked to this character, we performed
      an association mapping study with a candidate gene approach. We developed an
      original unstructured population with a broad genetic basis to avoid the pitfall
      of false positive detection due to population stratification. We genotyped 109
      SNPs located in 17 candidate genes - mostly carotenoid biosynthesis genes - on
      380 individuals, and tested the association with carotenoid contents and color
      components. Total carotenoids and beta-carotene contents were significantly
      associated with genes zeaxanthin epoxydase (ZEP), phytoene desaturase (PDS) and
      carotenoid isomerase (CRTISO) while alpha-carotene was associated with CRTISO and
      plastid terminal oxidase (PTOX) genes. Color components were associated most
      significantly with ZEP. Our results suggest the involvement of the couple
      PDS/PTOX and ZEP in carotenoid accumulation, as the result of the metabolic and
      catabolic activities respectively. This study brings new insights in the
      understanding of the carotenoid pathway in non-photosynthetic organs.

PMID- 25614990
TI  - Comparing the effect of non-medical mechanical restraint preventive factors
      between psychiatric units in Denmark and Norway.
AB  - BACKGROUND: The use of mechanical restraint (MR) is controversial, and large
      differences regarding the use of MR are often found among countries. In an
      earlier study, we observed that MR was used twice as frequently in Denmark than
      Norway. AIMS: To examine how presumed MR preventive factors of non-medical origin
      may explain the differing number of MR episodes between Denmark and Norway.
      METHODS: This study is a cross-sectional survey of psychiatric units. Linear
      regression was used to assess the confounding effects of the MR preventive
      factors, i.e. whether a difference in the impact of these factors is evident
      between Denmark and Norway. RESULTS: Six MR preventive factors confounded
      [?exp(B)> 10%] the difference in MR use between Denmark and Norway, including
      staff education (- 51%), substitute staff (- 17%), acceptable work environment (-
      15%), separation of acutely disturbed patients (13%), patient-staff ratio (-
      11%), and the identification of the patient's crisis triggers (- 10%).
      CONCLUSIONS: These six MR preventive factors might partially explain the
      difference in the frequency of MR episodes observed in the two countries, i.e.
      higher numbers in Denmark than Norway. One MR preventive factor was not supported
      by earlier research, the identification of the patient's crisis triggers;
      therefore, more research on the mechanisms involved is needed. CLINICAL
      IMPLICATIONS: None of the six MR preventive factors presents any adverse effects;
      therefore, units in Denmark and Norway may consider investigating the effect of
      implementing, the identification of the patient's crisis triggers, an increased
      number of staff per patient, increased staff education, a better work environment
      and reduced use of substitute staff in practice.

PMID- 25614991
TI  - Liver stiffness and portal blood flow modifications induced by a liquid meal
      consumption: pathogenetic mechanisms and clinical relevance.
AB  - OBJECTIVE: The correlation between liver stiffness (LS) variations and portal
      blood flow (PBF) modifications induced by a standardized liquid meal consumption
      and the clinical relevance of this matter are two aspects not yet fully
      elucidated. Herein, we evaluated the variations of LS and PBF after a
      standardized liquid meal intake in patients with chronic liver disease. MATERIAL
      AND METHODS: PBF and LS were determined after an overnight fasting period in 54
      patients. They were divided in three groups according to baseline LS (absent,
      moderate, and severe). They consumed 200 ml of water and a standardized liquid
      meal (300 Kcal/200 ml) after 60 min. PBF and LS were measured at 30 min after
      water and liquid meal consumption. RESULTS: In all groups, LS and PBF values
      significantly increased only after meal consumption. A significant correlation
      between baseline LS values and post-meal increase of LS was observed. Moreover,
      higher basal stiffness values were associated to a larger increase of LS
      variation after meal consumption. The effect of the meal on LS remained
      statistically significant after multiple regression analysis. A significant
      correlation between increase of LS and PBF was found in patients with absent and
      moderate baseline LS. Nine patients (17%) switched from a lower to a higher level
      of LS after meal consumption. CONCLUSION: A low calories/low-volume meal is
      capable of significantly increasing LS regardless of the grade of stiffness,
      determining a reclassification rate of 17%. In presence of minimal or moderate
      stiffness, the increase of LS is significantly correlated with the augment of
      PBF.

PMID- 25614992
TI  - Structure and binding of the C-terminal segment of R9AP to lipid monolayers.
AB  - Phototransduction cascade takes place in disc membranes of photoreceptor cells.
      Following its activation by light, rhodopsin activates the G-protein transducin
      causing the dissociation of its GTP-bound alpha-subunit, which in turn activates
      phosphodiesterase 6 (PDE6) leading to the hyperpolarization of photoreceptor
      cells. PDE6 must then be inactivated to return to the dark state. This is
      achieved by a protein complex which is presumably anchored to photoreceptor disc
      membranes by means of the transmembrane C-terminal segment of RGS9-1-Anchor
      Protein (R9AP). Information on the secondary structure and membrane binding
      properties of the C-terminal segment of R9AP is not yet available to further
      support its role in the membrane anchoring of this protein. In the present study,
      circular dichroism and infrared spectroscopy measurements have allowed us to
      determine that the C-terminal segment of human and bovine R9AP adopts an alpha
      helical structure in solution. Moreover, this C-terminal segment has shown
      affinity for most of the phospholipids typical of photoreceptor membranes. In
      fact, the physical state and the type of phospholipid as well as electrostatic
      interactions influence the binding of the human and bovine peptides to
      phospholipid monolayers. In addition, these measurements revealed that the human
      peptide has a high affinity for saturated phosphocholine, which may suggest a
      possible localization of R9AP in photoreceptor microdomains. Accordingly,
      infrared spectroscopy measurements have allowed determining that the C-terminal
      segment of R9AP adopts an ordered alpha-helical structure in the presence of
      saturated phospholipid monolayers. Altogether, these data are consistent with the
      typical alpha-helical secondary structure and behavior observed for transmembrane
      segments and with the proposed role of membrane anchoring of the C-terminal
      segment of human and bovine R9AP. 

PMID- 25614993
TI  - Correction to Natural occurrence of organofluorine and other constituents from
      Streptomyces sp. TC1.

PMID- 25614994
TI  - "Moonlighting" GAPDH Protein Localizes with AMPA Receptor GluA2 and L1 Axonal
      Cell Adhesion Molecule at Fiber Cell Borders in the Lens.
AB  - PURPOSE: The canonical role of glyceraldehyde phosphate dehydrogenase (GAPDH) is
      as an enzyme in glycolysis. GAPDH is also a principal "moonlighting" protein with
      additional roles at diverse sites in a variety of cells. Surface GAPDH on
      mammalian, yeast, and bacterial cells acts as a receptor and also mediates cell
      contacts. In neurons, extracellular GAPDH localizes at synapses. Two GAPDH
      binding partners at synapses are alpha-Amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid glutamate receptor (AMPA) GluA2 subunit at dendritic
      spines and L1 cell adhesion molecule at pre-synaptic membranes, and both proteins
      are also expressed in lenses. Fiber cell membrane protrusions and dendritic
      spines have similar size, shape, and spacing, contain F-actin, and express
      clathrin/AP-2 Adaptor at their surfaces linked with Tyr-phosphatase STEP
      regulated endocytosis of AMPA/GluA2 receptors. AMPA receptors work with NMDA (N
      methyl-d-aspartate) and GABA (gamma-aminobutyric acid) receptors, calcium
      calmodulin kinase II (CaMKIIalpha), channel proteins, STEP, and ephrin receptors,
      which are also expressed in lenses. In neurons, coordinate AMPA/GluA2 receptor
      endocytosis with GAPDH is linked with disease. GAPDH was previously characterized
      as a fiber cell membrane protein and shown to decrease substantially in interior
      fiber cells in human age-related cataract. Here, we examined GAPDH spatial
      expression in healthy lenses in two vertebrate species. METHODS: In situ methods
      were used to examine GAPDH expression in lenses of healthy young adult rabbits
      and chickens. Immunoblots were used to detect L1 in lenses. RESULTS: The present
      study demonstrated that GAPDH is present at fiber cell borders in adult rabbit
      and chicken lenses with evidence of focal concentrations along the fiber cell
      perimeter, and overlapped with detection of p-Tyr-GluA2, L1, STEP, actin and
      clathrin. We observed that L1-140 kDa was the prominent form in lens.
      CONCLUSIONS: Our findings indicate investigations into GAPDH "moonlighting"
      activities similar to its role in cell-cell interactions at neuron surfaces are
      warranted in the lens.

PMID- 25614995
TI  - Re: Moore EK, Irvine LM. 2014. The impact of maternal age over forty years on the
      caesarean section rate: six year experience at a busy district general hospital.
      Journal of Obstetrics and Gynaecology 34:238-240.

PMID- 25614996
TI  - A qualitative study of how patients with type 2 diabetes use an electronic stand
      alone personal health record.
AB  - BACKGROUND: Patient use of personal health records (PHRs) to manage their health
      information has been proposed to enhance patient knowledge and empower patients
      to make changes in their self-care behaviors. However, there remains a gap in
      understanding about patients' actual PHR use behaviors. The purpose of this
      qualitative study was to explore how patients with type 2 diabetes used a PHR to
      manage their diabetes-related health information for self-care. MATERIALS AND
      METHODS: Fifty-nine patients with type 2 diabetes were interviewed 3-6 months
      after receiving initial training on a free-of-charge, Web-based PHR. Interviews
      were audio-recorded, transcribed, and analyzed using an iterative process of in
      vivo coding, categorization, and theme development. RESULTS: Nine themes emerged,
      three of which expressed positive experiences: complete and accessible record;
      increased awareness; and behavioral changes. The remaining six themes expressed
      negative experiences: out of sight, out of mind; I would have used it if I were
      sicker; economic, infrastructure, and computer literacy barriers; lack of patient
      provider engagement; double tracking; and privacy and security concerns.
      CONCLUSIONS: Despite some potential positive benefits resulting from PHR use,
      several barriers inhibited sustained and effective use over time. Provider and
      patient education about the benefits of PHR use and about the potential for
      filling in information gaps in the provider-based record is key to engage
      patients and stimulate PHR adoption and use.

PMID- 25614997
TI  - A synthesis of the theory of silencing the self and the social ecological model:
      understanding gender, race, and depression in African American women living with
      HIV infection.
AB  - The challenges that face African American women living with HIV are immense.
      African American women continue to be disproportionately infected and affected by
      this chronic and life-threatening infection in a complex context of individual
      experience, interactions with the environment, formal and informal support
      systems, and cultural belief systems. This article identifies the Theory of
      Silencing the Self (STS) and a widely known model, the Social Ecological Model
      (SEM), as a synthesized explanatory framework in helping nurses understand how to
      address research questions and clinical care that is congruent with the
      experience of African American women living with HIV infection. In synthesizing
      the components of these two frameworks, an explanation of the relationship
      between disempowerment and depression in this population will be uncovered as a
      key component to making relationships at the individual, family, and community
      level better. Helping African American women living with HIV infection to explore
      and address how choosing to be silent across their life systems will advance
      healthcare adherence as we currently know it to improved self-management of a
      chronic, gender-specific, culturally-bound experience of depression. 

PMID- 25614998
TI  - Unexpectedly strong magnetic anisotropy in a mononuclear eight-coordinate
      cobalt(II) complex: a theoretical exploration.
AB  - Ab initio methods have been used to explore the unexpectedly strong magnetic
      anisotropy and the magnetostructural correlations in mononuclear eight-coordinate
      complex [Co(II)(12-crown-4)2](2+). Our calculations showed that both decreasing
      alpha and increasing phi may enhance its magnetic anisotropy, which was
      rationalized by the qualitative theory proposed by Long and co-workers. Moreover,
      we deduced that the |D| value of [Co(II)(12-crown-4)2](2+) with alpha = 52
      degrees  and phi = 43 degrees  is the largest one. 

PMID- 25614999
TI  - Sorting it out: what JNC 8 is and what it is not.
AB  - The landscape for hypertension guideline development and dissemination has
      changed. The intense debate surrounding the recent JNC 8 publication obscures the
      value this guideline offers to providers managing hypertension. Recommendations
      published by the panel appointed to JNC 8, when interpreted and applied as
      intended, can indeed guide hypertension management. The purpose of this
      commentary is to pare down what the JNC 8 publication is and what is not, so as
      to transcend the controversy and foster application of these guidelines to
      clinical practice.  

PMID- 25615000
TI  - Emergence of BCR-ABL kinase domain mutations associated with newly diagnosed
      chronic myeloid leukemia: a meta-analysis of clinical trials of tyrosine kinase
      inhibitors.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKIs) are a mainstay of treatment for
      patients suffering from chronic myeloid leukemia (CML). Testing for various
      mutations in the BCR-ABL gene may help predict lack of response to specific TKIs
      where resistance has developed. OBJECTIVE: To estimate the emergence of BCR-ABL
      kinase domain mutations associated with newly diagnosed CML patients exposed to
      first-line TKI treatment. METHODS: Published studies were identified using a
      structured search of online databases. Original research studies were included if
      they reported the incidence of specific BCR-ABL kinase domain point mutations
      after first-line TKI treatment failure or baseline mutations for second-line TKI
      treatment following first-line treatment failure. Meta-analysis of mutation rates
      across studies was based on DerSimonian and Laird's random-effects model.
      RESULTS: Of 1,323 citations, 12 studies met the inclusion criteria, involving a
      total of 1,698 patients. Overall mutation rates (95% CI) were imatinib 9.7% (6.2%
      13.3%); dasatanib 1.7% (0.0%-4.3%); and nilotinib 3.3% (0.0%-7.7%). The most
      common specific mutations were T315I, E255K, and M351T. T315I mutations
      constituted 58% (7 of 12) of dasatinib-related mutations and 13% (15 of 117) of
      imatinib-related mutations. CONCLUSIONS: Lack of response to TKIs associated with
      mutation in the BCR-ABL gene was significantly higher in imatinib-treated
      patients, and all mutations arose after treatment. T315I was a common treatment
      emergent mutation. Further research is needed to assess the prognostic value of
      testing for mutations and the economic implications of treatment-emergent
      mutations.

PMID- 25615001
TI  - A randomized telephone intervention trial to reduce primary medication
      nonadherence.
AB  - BACKGROUND: Primary medication nonadherence (PMN), defined as patients not
      picking up an initial prescription, can limit the effectiveness of therapy for
      chronic conditions. Effective interventions to reduce PMN have not been widely
      studied or implemented. OBJECTIVE: To evaluate the ability of an additional nurse
      directed telephone intervention to reduce PMN in a cohort of patients with
      persistent nonadherence after repeated pharmacy-based outreach. METHODS: Patients
      in the Geisinger Health System receiving new (i.e., initially prescribed)
      prescriptions sent to CVS pharmacies for medications treating asthma,
      hypertension, diabetes, or hyperlipidemia were identified. As part of existing
      programs, all patients received 2 automated and 1 live call from CVS pharmacies
      encouraging them to pick up their prescriptions; those who had canceled their
      prescriptions or had not picked them up after the 3 pharmacy interventions were
      eligible for this study. Patients were then randomized, and the intervention
      group received telephone outreach from a nursing call center to assess reasons
      for PMN and encourage pickup of prescriptions, with up to 3 attempts to reach
      each patient. Medication pickup rates were compared across the intervention and
      control groups. RESULTS: Initial PMN rates in the overall population were 6%,
      lower than previously observed in other studies. A total of 290 patients had not
      picked up their prescriptions after 3 calls from the pharmacy and were enrolled
      in the study: 142 in the intervention group and 148 controls. The intervention
      did not change the rate at which patients picked up their prescriptions: 25% of
      intervention patients did so compared with 24% of control patients. Multivariate
      models adjusting for patient characteristics and medication classes did not
      change the results. CONCLUSIONS: In a population of patients who had not picked
      up new prescriptions after 3 calls from the pharmacy, additional nurse-directed
      outreach did not improve primary medication adherence. Re-engagement with the
      prescribing clinician may be needed to improve adherence in this patient
      population. The low rate of PMN in the overall population differed from prior
      studies in this setting and others and should be assessed in future research.

PMID- 25615002
TI  - Quality process measures for rheumatoid arthritis: performance from members
      enrolled in a national health plan.
AB  - BACKGROUND: Health care quality problems are reflected in the underuse, overuse,
      and misuse of health care services. There is evidence suggesting that the quality
      of rheumatoid arthritis (RA) patient care is suboptimal, which has spurred the
      development of a number of systematic quality improvement metrics. OBJECTIVE: To
      investigate a quality process measurement set in a sample of commercially insured
      RA patients. METHODS: Medical, pharmacy, and laboratory claims for members with
      an RA diagnosis (ICD-9-CM 714.x) during calendar years 2008 through 2012 were
      extracted from the Optum Clinformatics Data Mart database. Eight process quality
      measures focused on RA patient response and tolerance to therapy were examined in
      the claims database. Measures were calculated for individual calendar years from
      2009 to 2012, inclusive. RESULTS: The majority of adult RA patients received at
      least 1 prescription for a disease-modifying antirheumatic drug (DMARD) across
      the 4 measurement years: range = 78.5%-81.6%. Erythrocyte sedimentation rate and
      C-reactive protein testing were also evident in the majority of the sample, with
      67.1%-72.2% of newly diagnosed RA patients receiving baseline testing, and 56.0%
      58.7% of existing RA patients receiving annual testing. Among methotrexate users,
      liver function tests were performed in 74.5%-75.7% of treated patients, serum
      creatinine tests in 70.1%-72.6% of patients, and complete blood count tests in
      74.5%-76.0% of patients. Additionally, most patients initiating a new DMARD had a
      claim for a baseline serum creatinine test (68.0%-70.3%) and baseline liver
      function test (69.3%-71.0%). CONCLUSIONS: Findings suggest that a majority of RA
      patients are attaining patient quality process measures, although a considerable
      proportion of patients (approximately 25%) may be receiving suboptimal care.
      Further studies are warranted to understand whether attainment of these measures
      translates into better outcomes.

PMID- 25615003
TI  - Evaluation of quality indicators for Dutch community pharmacies using a
      comprehensive assessment framework.
AB  - BACKGROUND: In 2008, the Dutch Health Care Transparency Programme (Zichtbare
      Zorg) was set up to develop and apply quality indicators (QIs) for health care.
      These QIs serve a range of purposes and can be categorized into those for
      internal use--for meeting quality standards and to continuously measure
      improvement (formative)--and external use--to enable patients and health
      insurance companies to distinguish between health care providers (summative). In
      order to assess the validity of QIs, a comprehensive Indicator Assessment
      Framework (IAF) was developed. This framework specifies the following criteria
      for validation: content validity, absence of selection bias, absence of
      measurement bias, and statistical reliability. Because of the intended summative
      use, the IAF was used for structural assessment of the QIs set for Dutch
      community pharmacists. OBJECTIVE: To assess the validity of the current set of 52
      QIs for community pharmacies using the IAF. METHODS: An expert panel applied the
      IAF criteria to the set of QIs collected in 1,807 Dutch community pharmacies on
      their performance in 2011. The QIs were judged as meeting, partly meeting, or not
      meeting the requirements regarding these criteria. The judgments were evaluated
      for QI type (structure, process, or outcome) and for predefined domains. RESULTS:
      Thirteen QIs (25%) were judged as meeting the requirements for all criteria.
      Among them were 12 structure indicators and 1 process indicator. For process
      indicators, the criterion for measurement bias poorly met the requirements, and
      content validity was unsatisfactory for outcome indicators. The 13 overall valid
      QIs covered 6 out of 10 predefined domains: continuity of care, clinical risk
      management, compounding, dispensing of medication, management, and quality
      management. CONCLUSIONS: When subjecting the QI set for community pharmacies to
      the requirements of the IAF, only a quarter of the QIs met all requirements. To
      increase the number of valid process and outcome indicators, meaningful aspects
      for the outcome of pharmaceutical care have to be defined, and uniform
      measurement of relevant processes has to be implemented.

PMID- 25615004
TI  - Influence of treatment complexity on adherence and incidence of blips in HIV/HCV
      coinfected patients.
AB  - BACKGROUND: The addition of antihepatitis C therapy to highly active
      antiretroviral treatment (HAART) in human immunodeficiency virus (HIV)/hepatitis
      C virus (HCV) coinfected patients leads to an increase in the treatment
      complexity that may result in decreased adherence. Blips, defined as intermittent
      episodes of detectable low-level HIV viremia, may be an indication of poor
      adherence to HAART. OBJECTIVES: To (a) determine the influence of adding anti-HCV
      therapy to HAART on complexity index, adherence, and incidence of blips and (b)
      determine complexity index and adherence in patient subgroups based on anti-HCV
      therapy. METHODS: We conducted a prospective 2-center observational study.
      HIV/HCV coinfected patients under antiretroviral treatment who started anti-HCV
      bi-therapy or triple therapy between January 2011 and December 2013 were
      included. Patients were excluded if they were virologically uncontrolled (HIV
      viral load greater than 50 copies RNA/mL) or if they had changed antiretroviral
      treatment in the 6 months prior to the introduction of anti-HCV therapy. Data
      were collected before and after the addition of anti-HCV therapy to HAART. The
      main variables were complexity index, incidence of blips, and adherence. The
      complexity index was based on a score that utilized the number of pills per day,
      dosing schedule, dosage form, and any specific instructions linked to use of the
      drug. Blips were defined as a detectable HIV-RNA level ( greater than 50
      copies/mL but no more than 1,000 copies/mL) occurring between 2 negative assays.
      Medication adherence was assessed using electronic pharmacy refill records. The
      threshold for optimal adherence was defined at 95% and above. Differences in the
      variables collected were assessed before and after the addition of anti-HCV
      therapy to HAART.R ESULTS: A total of 66 patients were included in the study.
      Based on the complexity index, the median value before and after the addition of
      anti-HCV therapy to HAART was 4.2 (interquartile range [IQR] = 3.5-5.5) and 11.5
      (IQR = 10.4-13.4), respectively. The median difference between both complexity
      indices was 6.9 (95% CI = 6.9-7, P  less than  0.001). After introducing the anti
      HCV therapy into HAART, the number of adherent patients decreased from 50 (75.8%)
      to 45 (68.2%, P  greater than 0.05), and 12 (18.2%) patients presented blips (P 
      less than  0.001). Subgroup analysis based on anti-HCV therapy showed that
      patients on boceprevir or telaprevir therapy had a higher complexity index, 16.8
      (IQR = 6.0-18.4), compared with patients on bi-therapy anti-HCV, 11.3 (IQR = 10.3
      12). The median difference was 6.0 (95% CI = 5.0-7.2, P  less than  0.001). The
      number of adherent patients decreased only in patients on bi-therapy from 42
      (79.2%) to 37 (69.8%, P  greater than 0.05). CONCLUSIONS: Adding anti-HCV therapy
      to antiretroviral treatment significantly increases treatment complexity and the
      incidence of blips. The introduction of anti-HCV therapy is also associated with
      a decrease in the number of adherent patients. The regimen complexity calculation
      may be useful for identifying patients who need more care from health care
      professionals or are at risk for failure to comply with treatment regimens.

PMID- 25615005
TI  - Economic burden associated with adverse events in patients with metastatic
      melanoma.
AB  - BACKGROUND: There are currently many approved agents for the treatment of
      metastatic melanoma (MM), the most aggressive form of skin cancer. Treatments may
      include systemic therapies such as ipilimumab, dacarbazine, temozolomide, high
      dose interleukin 2, interferon alpha, dacarbazine- or temozolomide-based
      combination chemotherapy/biochemotherapy, paclitaxel, paclitaxel/cisplatin, and
      paclitaxel/carboplatin, as well as the targeted therapies vemurafenib,
      dabrafenib, and trametinib for patients with BRAF V600 mutation. However, all
      treatment options are associated with different adverse events (AEs) and, in some
      instances, considerable toxicity. The occurrence of such treatment-related AEs
      can lead to higher health care resource utilization and increasing treatment and
      patient management costs. An understanding of the economic burden of these AEs
      will therefore enable better management of health care expenditures, not just for
      existing therapies, but also for new and novel treatments in development.
      OBJECTIVE: To estimate the incremental health care costs of specific AEs among
      patients with MM treated with paclitaxel, vemurafenib, ipilimumab, dacarbazine,
      temozolomide, high-dose interleukin 2, or interferon alpha, along with AEs known
      to be associated with dabrafenib and trametinib. METHODS: This cohort study
      employed a retrospective administrative claims-based analysis of MarketScan
      commercial and Medicare supplemental databases from July 1, 2004, to April 30,
      2012. Patients included those aged >= 18 years who had diagnosed melanoma (ICD-9
      CM code 172.xx)with >= 1 diagnosis of metastasis and >= 1 claim for any of the 7
      study treatments. Health care encounters for AEs of interest were based on ICD-9
      CM diagnosis/procedure codes. Incremental cost per AE was determined by comparing
      the 30-day expenditures in patients with the event to patients without the event
      based on a shadow event date. Multivariate generalized linear models (GLMs) with
      a log-link function and gamma distribution were utilized to control for baseline
      differences between groups. RESULTS: A total of 2,621 patients with MM were
      included. Mean age was 56.0 years (SD +/- 13.0); 64% were male; and 24% had a
      diagnosis of primary or secondary brain cancer at the time of MM diagnosis. GLM
      based estimate of 30-day incremental costs by AE category were metabolic, $9,135
      (95% CI = $6,404-$12,392); hematologic/lymphatic, $8,450 (95% CI = $6,528
      $10,633); cardiovascular, $6,476 (95% CI = $4,667-$8,541); gastrointestinal,
      $6,338 (95% CI = $4,740-$8,122); skin/subcutaneous, -$900 (95% CI = -$1,899
      $237); central nervous system/psychiatric, $5,903 (95% CI = $3,842-$8,313); and
      pain, $5,078 (95% CI = $3,392-$7,012). CONCLUSIONS: Incremental costs associated
      with many MM treatment-related AEs are substantial. New approaches to prevent
      and/or better manage these events may reduce overall health care costs.

PMID- 25615006
TI  - Cost-effectiveness analysis of allopurinol versus febuxostat in chronic gout
      patients: a U.S. payer perspective.
AB  - BACKGROUND: Gout is a chronic inflammatory condition associated with poor urate
      metabolism. Xanthine oxidase inhibitors such as allopurinol and febuxostat are
      recommended to reduce uric acid levels and to prevent gout attacks in adult
      patients. Under budget-driven constraints, health care payers are faced with the
      broader challenge of assessing the economic value of these agents for formulary
      placement. However, the economic value of allopurinol versus febuxostat has not
      be assessed in patients with gout over a 5-year time period in the United States.
      OBJECTIVE: To evaluate the cost-effectiveness of allopurinol versus febuxostat in
      adult patients with gout over a 5-year time period from a U.S. health care
      payer's perspective. METHODS: A Markov model was developed to compare the total
      direct costs and success of serum uric acid (sUA) level reduction associated with
      allopurinol and febuxostat. Treatment success was defined as patient achievement
      of a sUA level less than  6 mg/dL (0.36 mmol/L) at 6 months. Event probabilities
      were based on published phase III randomized clinical trials and included long
      term sequelae from open-label extension studies. A hypothetical cohort of 1,000
      adult gout patients with sUA levels of >= 8 mg/dL (0.48 mmol/L) who had received
      either allopurinol 300 mg or febuxostat 80 mg at model entry transitioned among
      the 4 health states defined by treatment success, treatment failure and switch,
      treatment dropout, and death. The length of each Markov cycle was 6 months. Costs
      were gathered from the RED BOOK, Medicare fee schedules, Healthcare Cost and
      Utilization Project's Nationwide Inpatient Sample, and for a limited number of
      inputs, expert consultation. Direct costs included treatment drug costs, costs
      for prophylaxis drugs, diagnostic laboratory tests, and the treatment and
      management of acute gout flare. Resource utilization was based on clinical
      evidence and expert consultation. All costs were inflated to 2014 U.S. dollars
      and were discounted at 3% in the base case. One-way sensitivity analysis and
      probabilistic sensitivity analyses (PSAs) were performed to assess the robustness
      of the results. RESULTS: The total per patient cost incurred over 5 years was
      $50,295 for febuxostat and $48,413 for allopurinol, with an incremental total
      cost of $1,882. The expected percentage of treatment success during the 5-year
      period was 72 for febuxostat and 42 for allopurinol, resulting in an incremental
      percentage of treatment success of 30. The estimated incremental cost
      effectiveness ratio for febuxostat compared with allopurinol was $6,322 per
      treatment success over a 5-year time period. The one-way sensitivity analysis
      indicated that the results were sensitive to probability of treatment success for
      allopurinol, probability of treatment dropouts for both allopurinol and
      febuxostat, and the probability of failure and switch to allopurinol. PSAs
      demonstrated that at a willingness-to-pay threshold of $50,000 per treatment
      success, febuxostat was cost-effective compared with allopurinol. CONCLUSIONS:
      Febuxostat was found to be a cost-effective option compared with allopurinol
      based on a U.S. payer perspective.

PMID- 25615007
TI  - Nanophase separation in monomolecularly thin water-ethanol films controlled by
      graphene.
AB  - Control over nanoscale patterning of ultrathin molecular films plays an important
      role both in natural as well as artificial nanosystems. Here we report on
      nanophase separated patterns of water and ethanol within monomolecularly thin
      films confined between the cleavage plane of mica and single or a few layers of
      graphene. Employing scanning force microscopy of the graphene layers conforming
      to the molecular films we quantify the patterns using the ethanol-water cross
      correlation and the autocorrelation of domain wall directions. They reveal that
      lateral pattern dimensions grow and the domain walls stiffen upon increasing the
      thickness of the graphene multilayers. We attribute the control of the patterns
      through the graphene layers to the competition between the mechanical deformation
      energy of the graphene sheets and the electrostatic repulsion of dipoles normal
      to the interface. The latter results from charge transfer between graphene and
      the molecules confined between mica and graphene. 

PMID- 25615008
TI  - Synthesis of 2,3-dideoxy-2-fluoro-2,3-endo-methylene- and 2,3-Dideoxy-2-fluoro-3
      C-hydroxymethyl-2,3-endo-methylene-pentofuranoses and their use in the
      preparation of conformationally locked bicyclic nucleosides.
AB  - Construction of protected 2,3-dideoxy-2-fluoro-2,3-endo-methylene-pentofuranoses
      from d-glyceraldehyde and 2,3-dideoxy-2-fluoro-3-C-hydroxymethyl-2,3-endo
      methylene-pentofuranoses from d-isoascorbic acid, via Simmons-Smith-type
      stereoselective cyclopropanations on the respective fluoroallyl alcohols, is
      described. Synthesis of the corresponding conformationally locked sugar modified
      uridine and guanosine nucleosides was achieved via Vorbruggen or Mitsunobu
      methodologies. Stereochemical confirmation of the novel nucleosides was performed
      on the basis of 2D NOESY NMR experiments. Analysis of 2',3'-dideoxy-2'-fluoro-3'
      C-hydroxymethyl-2',3'-endo-methylene-uridine by X-ray crystallography yielded the
      principal conformational parameters and indicated that the furanoid ring adopted
      an (o)E/(o)T1, East pucker. The uridine and guanosine nucleosides were found to
      be inactive in the hepatitis C virus (HCV) cell-based replicon assay, which was
      corroborated on examination of the corresponding nucleoside triphosphates against
      the HCV NS5B polymerase. 

PMID- 25615009
TI  - Electropolymerized highly photoconductive thin films of cyclopalladated and
      cycloplatinated complexes.
AB  - The complete characterization of novel electropolymerizable organometallic
      complexes is presented. These are newly synthesized cyclometalated complexes of
      general formula (PPy)M(O ? N)(n) (H(PPy) = 2-phenylpyridine, M = Pd(II) or
      Pt(II), H(O ? N)(n) = Schiff base). Polymeric thin films have been obtained from
      these complexes by electropolymerization of the triphenylamino group grafted onto
      the H(O ? N)(n) ancillary ligand. The redox behavior and the photoconductivity of
      both of the monomers (PPy)M(O ? N)(n) and the electropolymerized species have
      been investigated. The polymeric films of (PPy)M(O ? N)(n) have shown a very
      significant enhancement of photoconductivity when compared to their monomeric
      amorphous counterparts. The high stability of the obtained films strongly
      suggests that electropolymerization of cyclometalated complexes represents a
      viable deposition technique of quality thin films with improved photoconduction
      properties, hence opening the door to a new class of materials with suitable
      properties for optoelectronic applications.

PMID- 25615010
TI  - Near-Infrared Photoelectrochemical Conversion via Photoinduced Charge Separation
      in Supramolecular Complexes of Anionic Phthalocyanines with Li(+)@C60.
AB  - Two phthalocyanines possessing carboxylate groups ((TBA)4H2Pc.1 and (TBA)4H2Pc.2)
      form 1:2 supramolecular complexes with lithium cation-encapsulated C60
      (Li(+)@C60) [H2Pc.1(4-)/(Li(+)@C60)2 and H2Pc.2(4-)/(Li(+)@C60)2] in a polar
      mixed solvent. From the UV-vis spectral changes, the binding constants (K) were
      estimated as ca. 10(12) M(-2). Upon the photoexcitation of constructed
      supramolecular complexes, photoinduced electron transfer occurred to form the
      charge-separated (CS) state. The lifetime of the CS state was determined to be
      1.2 ms for H2Pc.2(4-)/(Li(+)@C60)2, which is the longest CS lifetime among the
      porphyrinoid/fullerene supramolecular complexes. H2Pc.1(4-)/(Li(+)@C60)2 also
      afforded the long-lived CS state of 1.0 ms. The spin state of the long-lived CS
      states was determined to be a triplet, as indicated by the EPR signal at g = 4.
      The reorganization energy (lambda) and the electronic coupling term were
      determined to be lambda = 1.70 eV, V = 0.15 cm(-1) from the temperature
      dependence of the rate constant for the charge recombination of the CS state of
      H2Pc.1(4-)/(Li(+)@C60)2. The energy of the CS state (0.49 eV) is much smaller
      than the reorganization energy, indicating that the back-electron-transfer
      process is located in the Marcus normal region. The small electronic coupling
      term results from the spin-forbidden back electron transfer due to the triplet CS
      state. Supramolecular complexes of anionic zinc phthalocyanines with Li(+)@C60
      were also prepared and investigated. The ZnPc.4(4-)/Li(+)@C60 supramolecular
      nanoclusters were assembled on the optically transparent electrode (OTE) of
      nanostructured SnO2 (OTE/SnO2) to construct the dye-sensitized solar cell. The
      IPCE (incident photon-to-photocurrent efficiency) values of OTE/SnO2/(ZnPc.4(4
      )/Li(+)@C60)n were much higher than the sum of the two IPCE values of the
      individual systems OTE/SnO2/(Li(+)@C60)n and OTE/SnO2/(ZnPc.4(4-))n, covering the
      near-infrared region. 

PMID- 25615012
TI  - A Monte Carlo investigation of cumulative dose measurements for cone beam
      computed tomography (CBCT) dosimetry.
AB  - Many studies have shown that the computed tomography dose index (CTDI100) which
      is considered as a main dose descriptor for CT dosimetry fails to provide a
      realistic reflection of the dose involved in cone beam computed tomography (CBCT)
      scans. Several practical approaches have been proposed to overcome drawbacks of
      the CTDI100. One of these is the cumulative dose concept. The purpose of this
      study was to investigate four different approaches based on the cumulative dose
      concept: the cumulative dose (1) f(0,150) and (2) f(0,infinity) with a small
      ionization chamber 20 mm long, and the cumulative dose (3) f100(150) and (4)
      f100(infinity) with a standard 100 mm pencil ionization chamber. The study also
      aimed to investigate the influence of using the 20 and 100 mm chambers and the
      standard and the infinitely long phantoms on cumulative dose measurements. Monte
      Carlo EGSnrc/BEAMnrc and EGSnrc/DOSXYZnrc codes were used to simulate a kV
      imaging system integrated with a TrueBeam linear accelerator and to calculate
      doses within cylindrical head and body PMMA phantoms with diameters of 16 cm and
      32 cm, respectively, and lengths of 150, 600, 900 mm. f(0,150) and f100(150)
      approaches were studied within the standard PMMA phantoms (150 mm), while the
      other approaches f(0,infinity) and f100(infinity) were within infinitely long
      head (600 mm) and body (900 mm) phantoms. CTDIinfinity values were used as a
      standard to compare the dose values for the approaches studied at the centre and
      periphery of the phantoms and for the weighted values. Four scanning protocols
      and beams of width 20-300 mm were used. It has been shown that the f(0,infinity)
      approach gave the highest dose values which were comparable to CTDIinfinity
      values for wide beams. The differences between the weighted dose values obtained
      with the 20 and 100 mm chambers were significant for the beam widths <120 mm, but
      these differences declined with increasing beam widths to be within 4%. The
      weighted dose values calculated within the infinitely long phantoms with both the
      chambers for the beam widths <=140 were within 3% of those within the standard
      phantoms, but the differences rose to be within 15% at wider beams. By comparing
      the approaches studied in this investigation with other methodologies taking into
      account the efficiency of the approach as a dose descriptor and the simplicity of
      the implementation in the clinical environment, the f(0,150) method may be the
      best for CBCT dosimetry combined with the use of correction factors.

PMID- 25615011
TI  - Molecular platform for design and synthesis of targeted dual-modality imaging
      probes.
AB  - We report a versatile dendritic structure based platform for construction of
      targeted dual-modality imaging probes. The platform contains multiple copies of
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out
      from a 1,4,7-triazacyclononane-N,N',N"-triacetic acid (NOTA) core. The specific
      coordination chemistries of the NOTA and DOTA moieties offer specific loading of
      (68/67)Ga(3+) and Gd(3+), respectively, into a common molecular scaffold. The
      platform also contains three amino groups which can potentiate targeted dual
      modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography;
      SPECT: single photon emission computed tomography; MRI: magnetic resonance
      imaging) when further functionalized by targeting vectors of interest. To
      validate this design concept, a bimetallic complex was synthesized with six
      peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1
      relaxivity per gadolinium atom was measured to be 15.99 mM(-1) s(-1) at 20 MHz.
      Further, the bimetallic agent demonstrated its anticipated in vivo stability,
      tissue distribution, and pharmacokinetic profile when labeled with (67)Ga. When
      conjugated with a model targeting peptide sequence, the trivalent construct was
      able to visualize tumors in a mouse xenograft model by both PET and MRI via a
      single dose injection. 

PMID- 25615013
TI  - What is your diagnosis? Urine crystals from a dog.

PMID- 25615014
TI  - Effectiveness of a personalized ventilation system in reducing personal exposure
      against directly released simulated cough droplets.
AB  - The inhalation intake fraction was used as an indicator to compare effects of
      desktop personalized ventilation and mixing ventilation on personal exposure to
      directly released simulated cough droplets. A cough machine was used to simulate
      cough release from the front, back, and side of a thermal manikin at distances
      between 1 and 4 m. Cough droplet concentration was measured with an aerosol
      spectrometer in the breathing zone of a thermal manikin. Particle image
      velocimetry was used to characterize the velocity field in the breathing zone.
      Desktop personalized ventilation substantially reduced the inhalation intake
      fraction compared to mixing ventilation for all investigated distances and
      orientations of the cough release. The results point out that the orientation
      between the cough source and the breathing zone of the exposed occupant is an
      important factor that substantially influences exposure. Exposure to cough
      droplets was reduced with increasing distance between cough source and exposed
      occupant. PRACTICAL IMPLICATIONS: The results from this study show that an
      advanced air distribution system such as personalized ventilation reduces
      exposure to cough-released droplets better than commonly applied overhead mixing
      ventilation. This work can inform HVAC engineers about different aspects of air
      distribution systems' performance and can serve as an aid in making critical
      design decisions.

PMID- 25615015
TI  - Genomewide analysis of small RNAs in nonembryogenic and embryogenic tissues of
      citrus: microRNA- and siRNA-mediated transcript cleavage involved in somatic
      embryogenesis.
AB  - Somatic embryogenesis (SE) is a process of somatic cells becoming
      dedifferentiated and generating embryos. SE has been widely used in biotechnology
      as a powerful way of regeneration and a model system for studying plant
      embryogenesis, but the controlling mechanisms of SE are far from clear. Here, we
      show the genomewide profiles of miRNAs/siRNAs and their target genes in
      nonembryogenic and embryogenic tissues of 'Valencia' sweet orange. By high
      throughput sequencing (HTS) of small RNAs and RNA degradome tags, we identified
      50 known and 45 novel miRNAs, 130 miniature inverted-repeat transposable elements
      (MITEs) derived, 94 other and 235 phased small interfering RNAs (siRNAs), as well
      as 203 target genes. The majority of the abundantly expressed miRNAs/siRNAs
      exhibit lower expression levels in embryogenic callus (EC) or during SE process
      than in nonembryogenic callus (NEC), which is supposed to derepress the target
      genes that are involved in development and stress response, thus to activate the
      biological processes required for cell differentiation. However, the conserved
      csi-miR156a/b, miR164b and 171c directed suppression of specific transcription
      factors (TFs) are supposed to inactivate the postembryonic growth thus to
      maintain normal SE. In this study, miRNA- and siRNA-mediated silencing of target
      genes was found under sophisticated regulation in citrus SE system; the
      enhancement effect of specific conserved miRNAs on SE was discussed, providing
      new clues for future investigation of mechanisms that control SE. 

PMID- 25615016
TI  - The 24th annual meeting of the European Tissue Repair Society (ETRS) in
      Edinburgh, Scotland.
AB  - From the 10th to 12th of September 2014, in the midst of the Scottish
      Independence debate, the European Tissue Repair Society descended on Edinburgh
      for their 24th Annual Meeting. In the beautiful and historic setting of the Royal
      College of Surgeons of Scotland, Professors David Thomas (Chair), Phil Stephens,
      Chris Lloyd, and their teams from Cardiff hosted an educational and inspiring
      program. 

PMID- 25615017
TI  - A hemicellulose-bound form of silicon with potential to improve the mechanical
      properties and regeneration of the cell wall of rice.
AB  - Silicon (Si) plays a large number of diverse roles in plants, but the structural
      and chemical mechanisms operating at the single-cell level remain unclear. We
      isolate the cell walls from suspension-cultured individual cells of rice (Oryza
      sativa) and fractionate them into three main fractions including cellulose (C),
      hemicellulose (HC) and pectin (P). We find that most of the Si is in HC as
      determined by inductively coupled plasma-mass spectrometry (ICP-MS), where Si may
      covalently crosslink the HC polysacchrides confirmed by X-ray photoelectron
      spectroscopy (XPS). The HC-bound form of Si could improve both the mechanical
      property and regeneration of the cell walls investigated by a combination of
      atomic force microscopy (AFM) and confocal laser scanning microscopy (CLSM). This
      study provides further evidence that HC could be the major ligand bound to Si,
      which broadens our understanding of the chemical nature of 'anomalous' Si in
      plant cell walls.

PMID- 25615018
TI  - On the function and fate of chloride ions in amyloidogenic self-assembly of
      insulin in an acidic environment: salt-induced condensation of fibrils.
AB  - Formation of amyloid fibrils is often facilitated in the presence of specific
      charge-compensating ions. Dissolved sodium chloride is known to accelerate
      insulin fibrillation at low pH that has been attributed to the shielding of
      electrostatic repulsion between positively charged insulin molecules by chloride
      ions. However, the subsequent fate of Cl(-) anions; that is, possible entrapment
      within elongating fibrils or escape into the bulk solvent, remains unclear. Here,
      we show that, while the presence of NaCl at the onset of insulin aggregation
      induces structural variants of amyloid with distinct fingerprint infrared
      features, a delayed addition of salt to fibrils that have been already formed in
      its absence and under quiescent conditions triggers a "condensation effect":
      amyloid superstructures with strong chiroptical properties are formed. Chloride
      ions appear to stabilize these superstructures in a manner similar to
      stabilization of DNA condensates by polyvalent cations. The concentration of
      residual chloride ions trapped within bovine insulin fibrils grown in 0.1 M NaCl,
      at pD 1.9, and rinsed extensively with water afterward is less than 1 anion per
      16 insulin monomers (as estimated using ion chromatography) implying absence of
      defined solvent-sequestered nesting sites for chloride counterions. Our results
      have been discussed in the context of mechanisms of insulin aggregation. 

PMID- 25615020
TI  - Specificity and inhibitory mechanism of andrographolide and its analogues as
      antiasthma agents on NF-kappaB p50.
AB  - Andrographolide (1) is a diterpenoid lactone with an alpha,beta-unsaturated
      lactone group that inhibits NF-kappaB DNA binding. Andrographolide reacts with
      the nucleophilic Cys62 of NF-kappaB p50 through a Michael addition at the
      Delta(12(13)) exocylic double bond to form a covalent adduct. Using computer
      docking, site-directed mutagenesis, and mass spectrometry, the noncovalent
      interactions between andrographolide and additional binding site residues other
      than Cys62 were found to be essential for the covalent incorporation of
      andrographolide. Furthermore, the addition reaction of andrographolide on Cys62
      was highly dependent on the redox conditions and on the vicinity of nearby,
      positively charged Arg residues in the conserved RxxRxR motif. The reaction
      mechanisms of several of the analogues were determined, showing that 14-deoxy
      11,12-didehydroandrographolide (8) reacts with NF-kappaB p50 via a novel
      mechanism distinct from andrographolide. The noncovalent interaction and redox
      environment of the binding site should be considered, in addition to the
      electrophilicity, when designing a covalent drug. Analogues similar in structure
      appear to use distinct reaction mechanisms and may have very different
      cytotoxicities, e.g., compound 6. 

PMID- 25615021
TI  - Low-voltage large-current ion gel gated polymer transistors fabricated by a "cut
      and bond" process.
AB  - A "cut and bond" process using a commercial die bonder was developed for
      fabricating ion gel gated organic thin-film transistors (OTFTs). It addresses the
      issues of damaging or contaminating the channel layer when depositing the ion gel
      layer on top in conventional fabrication processes. The formed isolated
      dielectric regions can help to eliminate possible lateral electric field coupling
      through the dielectric layer when several devices are integrated to construct
      functional circuits. The fabricated OTFTs provide mA-level ON current, and an
      ON/OFF current ratio higher than 10(5) with the gate swing voltage of less than 3
      V. With the developed process, the ion gel OTFTs are integrated with inorganic
      light emitting diodes (LEDs) of different colors on plastic substrate using the
      same die bonder, and the light emission of the LEDs can be modulated in a wide
      range from dark to high brightness with change of the gate voltage less than 3 V.

PMID- 25615019
TI  - A second Las17 monomeric actin-binding motif functions in Arp2/3-dependent actin
      polymerization during endocytosis.
AB  - During clathrin-mediated endocytosis (CME), actin assembly provides force to
      drive vesicle internalization. Members of the Wiskott-Aldrich syndrome protein
      (WASP) family play a fundamental role stimulating actin assembly. WASP family
      proteins contain a WH2 motif that binds globular actin (G-actin) and a central
      acidic motif that binds the Arp2/3 complex, thus promoting the formation of
      branched actin filaments. Yeast WASP (Las17) is the strongest of five factors
      promoting Arp2/3-dependent actin polymerization during CME. It was suggested that
      this strong activity may be caused by a putative second G-actin-binding motif in
      Las17. Here, we describe the in vitro and in vivo characterization of such Las17
      G-actin-binding motif (LGM) and its dependence on a group of conserved arginine
      residues. Using the yeast two-hybrid system, GST-pulldown, fluorescence
      polarization and pyrene-actin polymerization assays, we show that LGM binds G
      actin and is necessary for normal Arp2/3-mediated actin polymerization in vitro.
      Live-cell fluorescence microscopy experiments demonstrate that LGM is required
      for normal dynamics of actin polymerization during CME. Further, LGM is necessary
      for normal dynamics of endocytic machinery components that are recruited at
      early, intermediate and late stages of endocytosis, as well as for optimal
      endocytosis of native CME cargo. Both in vitro and in vivo experiments show that
      LGM has relatively lower potency compared to the previously known Las17 G-actin
      binding motif, WH2. These results establish a second G-actin-binding motif in
      Las17 and advance our knowledge on the mechanism of actin assembly during CME. 

PMID- 25615022
TI  - 1D polymeric platinum cyanoximate: a strategy toward luminescence in the near
      infrared region beyond 1000 nm.
AB  - We report the synthesis and properties of the first representative of a new class
      of PtL2 complexes with ambidentate mixed-donor cyanoxime ligands [L = 2-cyano-2
      oximino-N,N'-diethylaminoacetamide, DECO (1)]. Three differently colored
      polymorphs of "Pt(DECO)2" (3-5) were isolated, with the first two being
      crystallographically characterized. The dark-green complex [Pt(DECO)2]n (5)
      spontaneously forms in aqueous solution via aggregation of yellow monomeric
      complex 3 into the red dimer [Pt(DECO)2]2 (4), followed by further
      oligomerization into coordination polymer 5. A spectroscopic and light-scattering
      study revealed a "poker-chips"-type 1D polymeric structure of 5 in which units
      are held by noncovalent metallophilic interactions, forming a Pt---Pt wire. The
      polymer 5 shows a broad absorption at 400-900 nm and emission at unusually long
      wavelengths in the range of 1000-1100 nm in the solid state. The near-infrared
      (NIR) emission of polymer 5 is due to the formation of a small amount of
      nonstoichiometric mixed-valence Pt(II)/Pt(IV) species during synthesis. A
      featureless electron paramagnetic resonance spectrum of solid sample 5 recorded
      at +23 and -193  degrees C evidences the absence of Pt(III) states, and the
      compound represents a "solid solution" containing mixed-valence Pt(II)/Pt(IV)
      centers. Exposure of KBr pellets with 5% 5 to Br2 vapors leads to an immediate
      ~30% increase in the intensity of photoluminescence at 1024 nm, which confirms
      the role and importance of mixed-valence species for the NIR emission. Thus, the
      emission is further enhanced upon additional oxidation of Pt(II) centers, which
      improves delocalization of electrons along the Pt---Pt vector. Other polymorph of
      the "Pt(DECO)2" complex--monomer--did not demonstrate luminescent properties in
      solutions and the solid state. An excitation scan of 5 embedded in KBr tablets
      revealed an emission only weakly dependent on the wavelength of excitation. The
      NIR emission of quasi-1D complex 5 was studied in the range of -193 to +67 
      degrees C. Data showed a blue shift of lambdamax and a simultaneous increase in
      the emission line intensity with a temperature rise, which is explained by
      analogy with similar behavior of known quasi-1D K2[Pt(CN)4]-based solids, quantum
      dots, and quantum wells with delocalized carriers. The presented finding opens a
      route to a new class of platinum cyanoxime based NIR emissive complexes that
      could be used in the design of novel NIR emitters and imaging agents.

PMID- 25615023
TI  - Zinc oxide nanoparticles inhibit murine photoreceptor-derived cell proliferation
      and migration via reducing TGF-beta and MMP-9 expression in vitro.
AB  - OBJECTIVES: To investigate behaviour and expression of transforming growth factor
      beta (TGF-beta) and matrix metalloproteinases (MMP-9) in murine photoreceptor
      derived cells (661W) after incubation with zinc oxide (ZnO) nanoparticles.
      MATERIALS AND METHODS: We explored effects of ZnO nanoparticles on 661W cells
      using a real-time cell electronic sensing system, flow cytometry, multiple
      function microplate reading, real-time quantitative PCR detection system and
      enzyme-linked immunosorbent assay respectively. RESULTS: Our results indicate
      that ZnO nanoparticles induced overload of calcium and reactive oxygen species
      within cells, causing formation of apoptotic bodies, disruption of cell cycle
      distribution, and reduction in expression of TGF-beta and MMP-9, to suppress cell
      proliferation and migration. Our findings show that disruption of intracellular
      calcium homoeostasis and overproduction of reactive oxygen species were closely
      associated with reduction of TGF-beta and MMP-9 in 661W cells under ZnO
      nanoparticle treatment. CONCLUSIONS: Results of our study indicate that ZnO
      nanoparticles suppressed cell proliferation and migration, and reduced production
      of TGF-beta and MMP-9 at both gene and protein levels. Our findings contribute to
      the understanding of the molecular mechanisms that reduced TGF-beta and MMP-9
      levels inhibit cell proliferation and migration under ZnO nanoparticle influence.

PMID- 25615024
TI  - Case series of patients with chronic foot ulcers treated with autologous platelet
      rich plasma.
AB  - Treatment for patients with chronic wounds is entering a new era, and autologous
      platelet-rich plasma (PRP) is among the most promising treatments. PRP contains a
      concentration of platelets obtained by centrifuging the patient's blood. Because
      it contains fibrin and high concentrations of growth factors, PRP is known to
      promote wound healing. In this study, we present five patients with chronic foot
      ulcers successfully treated with PRP in our institution. The patients had various
      underlying diseases: diabetes (n = 2), peripheral arterial disease (n = 1), both
      diabetes and peripheral arterial disease (n = 1), and cutaneous polyarteritis
      nodosa (n = 1). Also, we provide a description of PRP's mechanisms, advantages,
      and limitations.

PMID- 25615025
TI  - Meta-analysis of association between the +49A/G polymorphism of cytotoxic T
      lymphocyte antigen-4 and thyroid associated ophthalmopathy.
AB  - PURPOSE OF THE STUDY: Cytotoxic-T lymphocyte antigen-4 (CTLA-4) has been shown to
      play an important role in the development and progression of thyroid associated
      ophthalmopathy (TAO). A number of case-control studies focused on the association
      between CTLA-4 +49A/G polymorphism and risk for TAO. But the results were not
      always consistent. So we performed a meta-analysis to evaluate the precise
      association between this polymorphism and risk for TAO. MATERIALS AND METHODS:
      All publications on the association between CTLA-4 +49A/G polymorphism and TAO
      were searched in the following electronic databases: PubMed, Embase, the Cochrane
      library and Chinese Biomedical Literature Database, with the last report up to
      May 2014. This meta-analysis was assessed by Review Manager 5.1. RESULTS: A total
      of 14 studies were involved in this meta-analysis, including 1128 cases and 2539
      controls. Overall, we found a significant association between CTLA-4 +49A/G
      polymorphism and TAO (G versus A: OR = 1.64, 95% CI = 1.40-1.92, p < 0.00001; GG
      versus AG + AA: OR = 2.02, 95% CI = 1.59-2.57, p < 0.00001; GG + AG versus AA: OR
      = 2.01, 95% CI = 1.66-2.43, p < 0.00001; GG versus AA: OR = 2.74, 95% CI = 1.83
      4.10, p < 0.00001; AG versus AA: OR = 1.75, 95% CI = 1.42-2.15, p < 0.00001). The
      results were not materially altered after the studies which did not fulfill Hardy
      Weinberg equilibrium were excluded. Significant association was also detected in
      both Caucasian and Asian populations in subgroup analysis divided by different
      ethnicity. CONCLUSION: Our meta-analysis supports the association between the
      CTLA-4 +49A/G polymorphism and TAO.

PMID- 25615026
TI  - The role of hypoxia and Morg1 in renal injury.
AB  - BACKGROUND: Renal hypoxia is known to play an important role in the
      pathophysiology of acute renal injury as well as in chronic kidney diseases. The
      mediators of hypoxia are the transcription factors HIF (hypoxia-inducible
      factors), that are highly regulated. Under normoxic conditions constitutively
      expressed HIF-alpha subunits are hydroxylated by prolyl hydroxylases (PHD1, PHD2,
      and PHD3) and subsequently degraded by proteasomes. MATERIALS AND METHODS: This
      narrative review is based on the material searched for and obtained via PubMed
      and MEDLINE up to January 2015. RESULTS: The MAPK organizer 1 (Morg1) has been
      identified to act as a scaffold protein of PHD3 and suppression of Morg1 leads to
      the stabilization of HIF-alpha, which forms in the absence of oxygen a
      heterodimer with HIF-beta, translocates to the nucleus and promotes the
      transcription of HIF target genes. CONCLUSIONS: This review summarizes the
      current knowledge regarding the role of hypoxia, HIF signalling, and Morg1 in
      acute and chronic renal injury.

PMID- 25615027
TI  - Personal technology use by U.S. military service members and veterans: an update.
AB  - OBJECTIVE: Although personal electronic devices, such as mobile phones,
      computers, and tablets, increasingly are being leveraged as vehicles for health
      in the civilian world, almost nothing is known about personal technology use in
      the U.S. military. In 2012 we conducted a unique survey of personal technologies
      used by U.S. military service members. However, with the rapidly growing
      sophistication of personal technology and changes in consumer habits, that
      knowledge must be continuously updated to be useful. Accordingly, we recently
      surveyed new samples of active duty service members, National Guard and Reserve,
      and veterans. MATERIALS AND METHODS: We collected data by online surveys in 2013
      from 239 active, inactive, and former service members. Online surveys were
      completed in-person via laptop computers at a large military installation and
      remotely via Web-based surveys posted on the Army Knowledge Online Web site and
      on a Defense Center Facebook social media channel. RESULTS AND CONCLUSIONS: We
      measured high rates of personal technology use by service members at home across
      popular electronic media. The most dramatic change since our earlier survey was
      the tremendous increase in mobile phone use at home for a wide variety of
      purposes. Participants also reported moderate non-work uses of computers and
      tablets while on recent deployment to Iraq and Afghanistan, but almost no mobile
      phone use, ostensibly because of military restrictions in the war zone. These
      latest results will enable researchers and technology developers target their
      efforts on the most promising and popular technologies for psychological health
      in the military.

PMID- 25615028
TI  - Prescription of dialysis in pediatric acute kidney injury.
AB  - Renal replacement therapy (RRT) is the most effective way of managing severe
      acute kidney injury (AKI) in critically ill patients. RRT application in children
      is currently increasing due to the progressive rise of severity of critical
      illness in these patients. The burden of mortality in RRT children with AKI
      significantly outweights 50% of the dialized patients (depending also on the
      diagnosis and on the presence of multiple organ dysfunction). Many aspects of
      pediatric AKI requiring RRT are currently uncertain or have never been
      investigated. Whereas much of the clinical information applied to the adult
      patients is commonly reported to pediatric critically ill children, recently a
      significant evolution of RRT technology and novel research on pediatric dialysis
      warranted interesting evidence and important innovation in this field. In
      particular, it is currently a matter of debate how pediatric dialysis should be
      prescribed, when it is indicated and which modality should be utilized. This
      review will describe different modalities currently available for pediatric RRT,
      the main mechanisms of solute and water removal, standard and innovative
      technology specifically relased for neonatal dialysis, the most common
      prescriptions applicable to dialized children, indications to start and stop RRT.

PMID- 25615030
TI  - Announcement: Increased length limit for rapid communications in Physical Review
      E.

PMID- 25615031
TI  - Excess free energy of supercooled liquids at disordered walls.
AB  - Using a thermodynamic integration scheme, we compute the excess free energy,
      gamma, of a glass-forming, binary Lennard-Jones liquid in contact with a frozen
      amorphous wall, formed by particles frozen into a similar structure as the
      liquid. We find that gamma is nonzero, becoming negative at low temperature. This
      indicates that the thermodynamics of the system is perturbed by the effect of the
      amorphous wall. 

PMID- 25615029
TI  - Barriers to antiretroviral therapy adherence and plasma HIV RNA suppression among
      AIDS clinical trials group study participants.
AB  - We conducted a secondary data analysis of 11 AIDS Clinical Trials Group (ACTG)
      studies to examine longitudinal associations between 14 self-reported
      antiretroviral therapy (ART) adherence barriers (at 12 weeks) and plasma HIV RNA
      (at 24 weeks) and to discern the relative importance of these barriers in
      explaining virologic detectability. Studies enrolled from 1997 to 2003 and
      concluded between 2002 and 2012. We included 1496 (54.2% of the original sample)
      with complete data. The most commonly selected barriers were "away from home"
      (21.9%), "simply forgot" (19.6%), "change in daily routine" (19.5%), and "fell
      asleep/slept through dosing time" (18.9%). In bivariate analyses, "too many pills
      to take" (OR=0.43, p<0.001), "wanted to avoid side effects" (OR=0.54, p=0.001),
      "felt drug was toxic/harmful" (OR=0.44, p<0.001), "felt sick or ill" (OR=0.49,
      p<0.001), "felt depressed/overwhelmed" (OR=0.58, p=0.004), and "problem taking
      pills at specified time" (OR=0.71, p=0.04) were associated with a lower odds of
      an undetectable HIV RNA. "Too many pills to take," "wanted to avoid side
      effects," "felt drug was toxic/harmful," "felt sick/ill,", and "felt
      depressed/overwhelmed" had the highest relative importance in explaining
      virologic detectability. "Simply forgot" was not associated with HIV RNA
      (OR=0.99, p=0.95) and was ninth in its relative importance. Adherence
      interventions should prioritize barriers with highest importance in explaining
      virologic outcomes rather than focusing on more commonly reported barriers. 

PMID- 25615032
TI  - How nanomechanical systems can minimize dissipation.
AB  - Information processing machines at the nanoscales are unavoidably affected by
      thermal fluctuations. Efficient design requires understanding how nanomachines
      can operate at minimal energy dissipation. Here we focus on mechanical systems
      controlled by smoothly varying potential forces. We show that optimal control
      equations come about in a natural way if the energy cost to manipulate the
      potential is taken into account. When such a cost becomes negligible, an optimal
      control strategy can be constructed by transparent geometrical methods which
      recover the solution of optimal mass transport equations in the overdamped limit.
      Our equations are equivalent to hierarchies of kinetic equations of a form well
      known in the theory of dilute gases. From our results, optimal strategies for
      energy efficient nanosystems may be devised by established techniques from
      kinetic theory. 

PMID- 25615033
TI  - Forces encountered by a sphere during impact into sand.
AB  - We describe direct measurements of the acceleration of an object impacting on a
      loosely packed granular bed under various pressures, using an instrumented
      sphere. The sphere acts as a noninvasive probe that measures and continuously
      transmits the acceleration as it penetrates into the sand, using a radio signal.
      The time-resolved acceleration of the sphere reveals the detailed dynamics during
      the impact that cannot be resolved from the position information alone. Because
      of the unobstructed penetration, we see a downward acceleration of the sphere at
      the moment the air cavity collapses. The compressibility of the sand bed is
      observed through the oscillatory behavior of the acceleration curve for various
      ambient pressures; it shows the influence of interstitial air on the compaction
      of the sand as a function of time. 

PMID- 25615034
TI  - Accounting for inertia effects to access the high-frequency microrheology of
      viscoelastic fluids.
AB  - We study the Brownian motion of microbeads immersed in water and in a
      viscoelastic wormlike micelles solution by optical trapping interferometry and
      diffusing wave spectroscopy. Through the mean-square displacement obtained from
      both techniques, we deduce the mechanical properties of the fluids at high
      frequencies by explicitly accounting for inertia effects of the particle and the
      surrounding fluid at short time scales. For wormlike micelle solutions, we
      recover the 3/4 scaling exponent for the loss modulus over two decades in
      frequency as predicted by the theory for semiflexible polymers. 

PMID- 25615035
TI  - Metric theory of nematoelastic shells.
AB  - We consider three-dimensional reshaping of a thin nematoelastic film upon nematic
      isotropic transition in the field of a charge one topological defect, leading to
      either cone or anticone (d-cone) shells. The analysis is based on the relation
      between the shell metric and the tensor order parameter under the assumption of
      no elastic deformation and volume change. The shape of the shell can be modified
      by doping, creating cones with curved generatrices. Anticones necessarily have an
      even number of radial creases. The curvature singularity at the apex is resolved
      due to decay of the nematic order parameter at the defect core. 

PMID- 25615036
TI  - Dynamics and limitations of spontaneous polyelectrolyte intrusion into a charged
      nanocavity.
AB  - We systematically investigate the spontaneous packaging mechanism of a single
      polyelectrolyte chain into an oppositely charged nanocavity by Langevin molecular
      dynamics simulations of a generic coarse-grained model. Intrusion dynamics and
      packaging rate, as well as the self-assembly process inside turn out to depend
      sensitively on the stiffness of the polyelectrolyte, the surface charge density
      inside the capsid, and the radius of the cavity. Further analysis shows that,
      depending on the stiffness, thermal fluctuations and charge inversion can be
      important factors to overcome barriers that slow down the intrusion and packaging
      dynamics. These results help advance our understanding of the function of charges
      on the inner surface of viral capsids and the possibility to design capsids as
      synthetic nanocarriers. 

PMID- 25615037
TI  - Probing turbulence intermittency via autoregressive moving-average models.
AB  - We suggest an approach to probing intermittency corrections to the Kolmogorov law
      in turbulent flows based on the autoregressive moving-average modeling of
      turbulent time series. We introduce an index Upsilon that measures the distance
      from a Kolmogorov-Obukhov model in the autoregressive moving-average model space.
      Applying our analysis to particle image velocimetry and laser Doppler velocimetry
      measurements in a von Karman swirling flow, we show that Upsilon is proportional
      to traditional intermittency corrections computed from structure functions.
      Therefore, it provides the same information, using much shorter time series. We
      conclude that Upsilon is a suitable index to reconstruct intermittency in
      experimental turbulent fields. 

PMID- 25615038
TI  - Method for estimating critical exponents in percolation processes with low
      sampling.
AB  - In phase-transition phenomena, the estimation of the critical point is crucial
      for the calculation of the various critical exponents and the determination of
      the universality class they belong to. However, this is not an easy task, since a
      large amount of realizations is needed to eliminate the noise in the data. In
      this paper, we introduce a novel method for the simultaneous estimation of the
      critical point p(c) and the critical exponent beta/nu, applied for the case of
      "explosive" bond percolation on two-dimensional square lattices and Erdos-Renyi
      networks. The results show that with only a few hundred realizations, it is
      possible to acquire accurate values for these quantities. Guidelines are given at
      the end for the applicability of the method to other cases as well.

PMID- 25615039
TI  - Boosting cooperation by involving extortion in spatial prisoner's dilemma games.
AB  - We study the evolution of cooperation in spatial prisoner's dilemma games with
      and without extortion by adopting the aspiration-driven strategy updating rule.
      We focus explicitly on how the strategy updating manner (whether synchronous or
      asynchronous) and also the introduction of extortion strategy affect the
      collective outcome of the games. By means of Monte Carlo simulations as well as
      dynamical cluster techniques, we find that the involvement of extortioners
      facilitates the boom of cooperators in the population (and whom can always
      dominate the population if the temptation to defect is not too large) for both
      synchronous and asynchronous strategy updating, in stark contrast to the other
      case, where cooperation is promoted for an intermediate aspiration level with
      synchronous strategy updating, but is remarkably inhibited if the strategy
      updating is implemented asynchronously. We explain the results by configurational
      analysis and find that the presence of extortion leads to the checkerboard-like
      ordering of cooperators and extortioners, which enable cooperators to prevail in
      the population with both strategy updating manners. Moreover, extortion itself is
      evolutionary stable, and therefore acts as the incubator for the evolution of
      cooperation. 

PMID- 25615040
TI  - Velocity autocorrelation of a free particle driven by a Mittag-Leffler noise:
      fractional dynamics and temporal behaviors.
AB  - We investigate the dynamical phase diagram of the generalized Langevin equation
      of the free particle driven by a Mittag-Leffler noise and show critical curves
      and a critical value of the exponent parameter of the Mittag-Leffler function
      that mark different dynamical regimes. By considering that the modeling of a
      Mittag-Leffer memory kernel corresponds to a power-law second-order memory
      kernel, we show that the generalized Langevin equation of the velocity
      autocorrelation function (VACF) is transformed in a fractional Langevin equation.
      In the superdiffusive case our results exhibit oscillations and negative
      correlations of the VACF that are not provided by the usual power-law noise
      model. 

PMID- 25615041
TI  - Two-point correlation function of an exclusion process with hole-dependent rates.
AB  - We consider an exclusion process on a ring in which a particle hops to an empty
      neighboring site with a rate that depends on the number of vacancies n in front
      of it. In the steady state, using the well-known mapping of this model to the
      zero-range process, we write down an exact formula for the partition function and
      the particle-particle correlation function in the canonical ensemble. In the
      thermodynamic limit, we find a simple analytical expression for the generating
      function of the correlation function. This result is applied to the hop rate
      u(n)=1+(b/n) for which a phase transition between high-density laminar phase and
      low-density jammed phase occurs for b>2. For these rates, we find that at the
      critical density, the correlation function decays algebraically with a
      continuously varying exponent b-2. We also calculate the two-point correlation
      function above the critical density and find that the correlation length diverges
      with a critical exponent nu=1/(b-2) for b<3 and 1 for b>3. These results are
      compared with those obtained using an exact series expansion for finite systems. 

PMID- 25615042
TI  - Reexamination of the nonperturbative renormalization-group approach to the
      Kosterlitz-Thouless transition.
AB  - We reexamine the two-dimensional linear O(2) model (phi4 theory) in the framework
      of the nonperturbative renormalization-group. From the flow equations obtained in
      the derivative expansion to second order and with optimization of the infrared
      regulator, we find a transition between a high-temperature (disordered) phase and
      a low-temperature phase displaying a line of fixed points and algebraic order. We
      obtain a picture in agreement with the standard theory of the Kosterlitz-Thouless
      (KT) transition and reproduce the universal features of the transition. In
      particular, we find the anomalous dimension eta(T(KT))?0.24 and the stiffness
      jump rho(s)(T(KT)(-))?0.64 at the transition temperature T(KT), in very good
      agreement with the exact results eta(T(KT))=1/4 and rho(s)(T(KT)(-))=2/pi, as
      well as an essential singularity of the correlation length in the high
      temperature phase as T->T(KT).

PMID- 25615043
TI  - Anisotropic interfacial tension, contact angles, and line tensions: a graphics
      processing-unit-based Monte Carlo study of the Ising model.
AB  - As a generic example for crystals where the crystal-fluid interface tension
      depends on the orientation of the interface relative to the crystal lattice axes,
      the nearest-neighbor Ising model on the simple cubic lattice is studied over a
      wide temperature range, both above and below the roughening transition
      temperature. Using a thin-film geometry L(x)*L(y)*L(z) with periodic boundary
      conditions along the z axis and two free L(x)*L(y) surfaces at which opposing
      surface fields +/-H(1) act, under conditions of partial wetting, a single planar
      interface inclined under a contact angle theta<pi/2 relative to the yz plane is
      stabilized. In the y direction, a generalization of the antiperiodic boundary
      condition is used that maintains the translational invariance in the y direction
      despite the inhomogeneity of the magnetization distribution in this system. This
      geometry allows a simultaneous study of the angle-dependent interface tension,
      the contact angle, and the line tension (which depends on the contact angle, and
      on temperature). All these quantities are extracted from suitable thermodynamic
      integration procedures. In order to keep finite-size effects as well as
      statistical errors small enough, rather large lattice sizes (of the order of 46
      million sites) were found to be necessary, and the availability of very efficient
      code implementation of graphics processing units was crucial for the feasibility
      of this study.

PMID- 25615044
TI  - Second laws for an information driven current through a spin valve.
AB  - We propose a physically realizable Maxwell's demon device using a spin valve
      interacting unitarily for a short time with electrons placed on a tape of quantum
      dots, which is thermodynamically equivalent to the device introduced by Mandal
      and Jarzynski [D. Mandal and C. Jarzynski, Proc. Natl. Acad. Sci. USA 109, 11641
      (2012)]. The model is exactly solvable and we show that it can be equivalently
      interpreted as a Brownian ratchet demon. We then consider a measurement-based
      discrete feedback scheme, which produces identical system dynamics, but possesses
      a different second law inequality. We show that the second law for discrete
      feedback control can provide a smaller, equal, or larger bound on the maximum
      extractable work as compared to the second law involving the tape of bits.
      Finally, we derive an effective master equation governing the system evolution
      for Poisson distributed bits on the tape (or measurement times, respectively) and
      we show that its associated entropy production rate contains the same physical
      statement as the second law involving the tape of bits.

PMID- 25615045
TI  - Pinning time statistics for vortex lines in disordered environments.
AB  - We study the pinning dynamics of magnetic flux (vortex) lines in a disordered
      type-II superconductor. Using numerical simulations of a directed elastic line
      model, we extract the pinning time distributions of vortex line segments. We
      compare different model implementations for the disorder in the surrounding
      medium: discrete, localized pinning potential wells that are either attractive
      and repulsive or purely attractive, and whose strengths are drawn from a Gaussian
      distribution; as well as continuous Gaussian random potential landscapes. We find
      that both schemes yield power-law distributions in the pinned phase as predicted
      by extreme-event statistics, yet they differ significantly in their effective
      scaling exponents and their short-time behavior. 

PMID- 25615046
TI  - Feedback network models for quantum transport.
AB  - Quantum feedback networks have been introduced in quantum optics as a framework
      for constructing arbitrary networks of quantum mechanical systems connected by
      unidirectional quantum optical fields, and has allowed for a system theoretic
      approach to open quantum optics systems. Our aim here is to establish a network
      theory for quantum transport systems where typically the mediating fields between
      systems are bidirectional. Mathematically, this leads us to study quantum
      feedback networks where fields arrive at ports in input-output pairs, making it a
      special case of the unidirectional theory where inputs and outputs are paired.
      However, it is conceptually important to develop this theory in the context of
      quantum transport theory-the resulting theory extends traditional approaches
      which tend to view the components in quantum transport as scatterers for the
      various fields, in the process allowing us to consider emission and absorption of
      field quanta by these components. The quantum feedback network theory is
      applicable to both Bose and Fermi fields, moreover, it applies to nonlinear
      dynamics for the component systems. We advance the general theory, but study the
      case of linear passive quantum components in some detail. 

PMID- 25615047
TI  - Transport and fluctuation-dissipation relations in asymptotic and preasymptotic
      diffusion across channels with variable section.
AB  - We study the asymptotic and preasymptotic diffusive properties of Brownian
      particles in channels whose section varies periodically in space. The effective
      diffusion coefficient D(eff) is numerically determined by the asymptotic behavior
      of the root mean square displacement in different geometries, considering even
      cases of steep variations of the channel boundaries. Moreover, we compared the
      numerical results to the predictions from the various corrections proposed in the
      literature to the well known Fick-Jacobs approximation. Building an effective one
      dimensional equation for the longitudinal diffusion, we obtain an approximation
      for the effective diffusion coefficient. Such a result goes beyond a perturbation
      approach, and it is in good agreement with the actual values obtained by the
      numerical simulations. We discuss also the preasymptotic diffusion which is
      observed up to a crossover time whose value, in the presence of strong spatial
      variation of the channel cross section, can be very large. In addition, we show
      how the Einstein's relation between the mean drift induced by a small external
      field and the mean square displacement of the unperturbed system is valid in both
      asymptotic and preasymptotic regimes.

PMID- 25615048
TI  - Effects of junctional correlations in the totally asymmetric simple exclusion
      process on random regular networks.
AB  - We investigate the totally asymmetric simple exclusion process on closed and
      directed random regular networks, which is a simple model of active transport in
      the one-dimensional segments coupled by junctions. By a pair mean-field theory
      and detailed numerical analyses, it is found that the correlations at junctions
      induce two notable deviations from the simple mean-field theory, which neglects
      these correlations: (1) the narrower range of particle density for phase
      coexistence and (2) the algebraic decay of density profile with exponent 1/2 even
      outside the maximal-current phase. We show that these anomalies are attributable
      to the effective slow bonds formed by the network junctions.

PMID- 25615049
TI  - Odd q-state clock spin-glass models in three dimensions, asymmetric phase
      diagrams, and multiple algebraically ordered phases.
AB  - Distinctive orderings and phase diagram structures are found, from
      renormalization-group theory, for odd q-state clock spin-glass models in d=3
      dimensions. These models exhibit asymmetric phase diagrams, as is also the case
      for quantum Heisenberg spin-glass models. No finite-temperature spin-glass phase
      occurs. For all odd q>=5, algebraically ordered antiferromagnetic phases occur.
      One such phase is dominant and occurs for all q>=5. Other such phases occupy
      small low-temperature portions of the phase diagrams and occur for 5<=q<=15. All
      algebraically ordered phases have the same structure, determined by an attractive
      finite-temperature sink fixed point where a dominant and a subdominant pair
      states have the only nonzero Boltzmann weights. The phase transition critical
      exponents quickly saturate to the high q value. 

PMID- 25615050
TI  - Nonequilibrium statistical mechanics of a two-temperature Ising ring with
      conserved dynamics.
AB  - The statistical mechanics of a one-dimensional Ising model in thermal equilibrium
      is well-established, textbook material. Yet, when driven far from equilibrium by
      coupling two sectors to two baths at different temperatures, it exhibits
      remarkable phenomena, including an unexpected "freezing by heating." These
      phenomena are explored through systematic numerical simulations. Our study
      reveals complicated relaxation processes as well as a crossover between two very
      different steady-state regimes. 

PMID- 25615051
TI  - Approach to asymptotically diffusive behavior for Brownian particles in media
      with periodic diffusivities.
AB  - We analyze the mean squared displacement of a Brownian particle in a medium with
      a spatially varying local diffusivity, which is assumed to be periodic. When the
      system is asymptotically diffusive, the mean-squared displacement, characterizing
      the dispersion in the system, is, at late times, a linear function of time. A
      Kubo-type formula is given for the mean-squared displacement, which allows the
      recovery of some known results for the effective diffusion constant D(e) in a
      direct way, but also allows an understanding of the asymptotic approach to the
      diffusive limit. In particular, as well as as computing the slope of a linear fit
      to the late-time mean-squared displacement, we find a formula for the constant
      where the fit intersects the y axis.

PMID- 25615052
TI  - Waiting time distribution for continuous stochastic systems.
AB  - The waiting time distribution (WTD) is a common tool for analyzing discrete
      stochastic processes in classical and quantum systems. However, there are many
      physical examples where the dynamics is continuous and only approximately
      discrete, or where it is favourable to discuss the dynamics on a discretized and
      a continuous level in parallel. An example is the hindered motion of particles
      through potential landscapes with barriers. In the present paper we propose a
      consistent generalization of the WTD from the discrete case to situations where
      the particles perform continuous barrier crossing characterized by a finite
      duration. To this end, we introduce a recipe to calculate the WTD from the Fokker
      Planck (Smoluchowski) equation. In contrast to the closely related first passage
      time distribution (FPTD), which is frequently used to describe continuous
      processes, the WTD contains information about the direction of motion. As an
      application, we consider the paradigmatic example of an overdamped particle
      diffusing through a washboard potential. To verify the approach and to elucidate
      its numerical implications, we compare the WTD defined via the Smoluchowski
      equation with data from direct simulation of the underlying Langevin equation and
      find full consistency provided that the jumps in the Langevin approach are
      defined properly. Moreover, for sufficiently large energy barriers, the WTD
      defined via the Smoluchowski equation becomes consistent with that resulting from
      the analytical solution of a (two-state) master equation model for the short-time
      dynamics developed previously by us [Phys. Rev. E 86, 061135 (2012)]. Thus, our
      approach "interpolates" between these two types of stochastic motion. We
      illustrate our approach for both symmetric systems and systems under constant
      force.

PMID- 25615053
TI  - Thermodynamic laws in isolated systems.
AB  - The recent experimental realization of exotic matter states in isolated quantum
      systems and the ensuing controversy about the existence of negative absolute
      temperatures demand a careful analysis of the conceptual foundations underlying
      microcanonical thermostatistics. Here we provide a detailed comparison of the
      most commonly considered microcanonical entropy definitions, focusing
      specifically on whether they satisfy or violate the zeroth, first, and second
      laws of thermodynamics. Our analysis shows that, for a broad class of systems
      that includes all standard classical Hamiltonian systems, only the Gibbs volume
      entropy fulfills all three laws simultaneously. To avoid ambiguities, the
      discussion is restricted to exact results and analytically tractable examples. 

PMID- 25615054
TI  - Anomalous cross-field diffusion in a magnetic trap.
AB  - We numerically simulated the diffusion of a charged Brownian particle confined to
      a plane under the action of an orthogonal magnetic field with intensity depending
      on the distance from a center. Despite its apparent simplicity, this system
      exhibits anomalous diffusion. For positive field gradients, radial and angular
      dynamics are asymptotically subdiffusive, with exponents given by simple
      analytical expressions. In contrast, when driven by a weakly decaying field, the
      particle attains normal diffusion only after exceedingly long superdiffusive
      transients. These mechanisms can be related to Bohm diffusion in magnetized
      plasmas. 

PMID- 25615055
TI  - Aperiodic compression and reconstruction of real-world material systems based on
      Wang tiles.
AB  - The paper presents a concept to compress and synthesize complex material
      morphologies that is based on Wang tilings. Specifically, a microstructure is
      stored in a set of Wang tiles and its reconstruction is performed by means of a
      stochastic tiling algorithm. A substantial part of the study is devoted to the
      setup of optimal parameters of the automatic tile design by means of parametric
      studies with statistical descriptors at heart. The performance of the method is
      demonstrated on four two-dimensional two-phase target systems, monodisperse media
      with hard and soft disks, sandstone, and high porosity metallic foam. 

PMID- 25615056
TI  - Nonequilibrium density matrix in quantum open systems: generalization for
      simultaneous heat and charge steady-state transport.
AB  - We suggest a generalization of the expression of the nonequilibrium (NE) density
      matrix obtained by Hershfield's method for the cases where both heat and charge
      steady-state currents are present in a quantum open system. The finite-size
      quantum system, connected to two temperature and particle reservoirs, is driven
      out of equilibrium by the presence of both a temperature gradient and a chemical
      potential gradient between the two reservoirs. We show that the NE density matrix
      is given by a generalized Gibbs-like ensemble and is in full agreement with the
      general results of the McLennan-Zubarev nonequilibrium ensembles. The extra
      nonequilibrium terms are related to the entropy production in the system and
      characterize the fluxes of heat and particle. An explicit example, for the lowest
      order expansion, is provide for a model system of noninteracting fermions. 

PMID- 25615057
TI  - Capturing the Landauer bound through the application of a detailed Jarzynski
      equality for entropic memory erasure.
AB  - The states of an overdamped Brownian particle confined in a two-dimensional
      bilobal enclosure are considered to correspond to two binary values: 0 (left
      lobe) and 1 (right lobe). An ensemble of such particles represents bits of
      entropic information. An external bias is applied on the particles, equally
      distributed in two lobes, to drive them to a particular lobe erasing one kind of
      bit of information. It has been shown that the average work done for the entropic
      memory erasure process approaches the Landauer bound for a very slow erasure
      cycle. Furthermore, the detailed Jarzynski equality holds to a very good extent
      for the erasure protocol, so that the Landauer bound may be calculated
      irrespective of the time period of the erasure cycle in terms of the effective
      free-energy change for the process. The detailed Jarzynski equality applied to
      two subprocesses, namely the transition from entropic memory state 0 to state 1
      and the transition from entropic memory state 1 to state 1, connects the work
      done on the system to the probability to occupy the two states under a time
      reversed process. In the entire treatment, the work appears as a boundary effect
      of the physical confinement of the system not having a conventional potential
      energy barrier. Finally, an analytical derivation of the detailed and classical
      Jarzynski equality for Brownian movement in confined space with varying width has
      been proposed. Our analytical scheme supports the numerical simulations presented
      in this paper. 

PMID- 25615058
TI  - Interference of identical particles and the quantum work distribution.
AB  - Quantum-mechanical particles in a confining potential interfere with each other
      while undergoing thermodynamic processes far from thermal equilibrium. By
      evaluating the corresponding transition probabilities between many-particle
      eigenstates we obtain the quantum work distribution function for identical bosons
      and fermions, which we compare with the case of distinguishable particles. We
      find that the quantum work distributions for bosons and fermions significantly
      differ at low temperatures, while, as expected, at high temperatures the work
      distributions converge to the classical expression. These findings are
      illustrated with two analytically solvable examples, namely the time-dependent
      infinite square well and the parametric harmonic oscillator. 

PMID- 25615059
TI  - Temperature-dependent thermal conductivities of one-dimensional nonlinear Klein
      Gordon lattices with a soft on-site potential.
AB  - The temperature-dependent thermal conductivities of one-dimensional nonlinear
      Klein-Gordon lattices with soft on-site potential (soft-KG) are investigated
      systematically. Similarly to the previously studied hard-KG lattices, the
      existence of renormalized phonons is also confirmed in soft-KG lattices. In
      particular, the temperature dependence of the renormalized phonon frequency
      predicted by a classical field theory is verified by detailed numerical
      simulations. However, the thermal conductivities of soft-KG lattices exhibit the
      opposite trend in temperature dependence in comparison with those of hard-KG
      lattices. The interesting thing is that the temperature-dependent thermal
      conductivities of both soft- and hard-KG lattices can be interpreted in the same
      framework of effective phonon theory. According to the effective phonon theory,
      the exponents of the power-law dependence of the thermal conductivities as a
      function of temperature are only determined by the exponents of the soft or hard
      on-site potentials. These theoretical predictions are consistently verified very
      well by extensive numerical simulations. 

PMID- 25615060
TI  - Failure of steady-state thermodynamics in nonuniform driven lattice gases.
AB  - To be useful, steady-state thermodynamics (SST) must be self-consistent and have
      predictive value. Consistency of SST was recently verified for driven lattice
      gases under global weak exchange. Here I verify consistency of SST under local
      (pointwise) exchange, but only in the limit of a vanishing exchange rate; for a
      finite exchange rate the coexisting systems have different chemical potentials. I
      consider the lattice gas with nearest-neighbor exclusion on the square lattice,
      with nearest-neighbor hopping, and with hopping to both nearest and next-nearest
      neighbors. I show that SST does not predict the coexisting densities under a
      nonuniform drive or in the presence of a nonuniform density provoked by a hard
      wall or nonuniform transition rates. The steady-state chemical potential profile
      is, moreover, nonuniform at coexistence, contrary to the basic principles of
      thermodynamics. Finally, I discuss examples of a pair of systems possessing
      identical steady states but which do not coexist when placed in contact. The
      results of these studies confirm the validity of SST for coexistence between
      spatially uniform systems but cast serious doubt on its consistency and
      predictive value in systems with a finite rate of particle exchange between
      coexisting regions exhibiting a nonuniform particle density. 

PMID- 25615061
TI  - Optimal performance of endoreversible quantum refrigerators.
AB  - The derivation of general performance benchmarks is important in the design of
      highly optimized heat engines and refrigerators. To obtain them, one may model
      phenomenologically the leading sources of irreversibility ending up with results
      that are model independent, but limited in scope. Alternatively, one can take a
      simple physical system realizing a thermodynamic cycle and assess its optimal
      operation from a complete microscopic description. We follow this approach in
      order to derive the coefficient of performance at maximum cooling rate for any
      endoreversible quantum refrigerator. At striking variance with the universality
      of the optimal efficiency of heat engines, we find that the cooling performance
      at maximum power is crucially determined by the details of the specific system
      bath interaction mechanism. A closed analytical benchmark is found for
      endoreversible refrigerators weakly coupled to unstructured bosonic heat baths:
      an ubiquitous case study in quantum thermodynamics. 

PMID- 25615062
TI  - Noncanonical statistics of a finite quantum system with non-negligible system
      bath coupling.
AB  - The canonical statistics describes the statistical properties of an open system
      by assuming its coupling with the heat bath is infinitesimal in comparison with
      the total energy in thermodynamic limit. In this paper, we generally derive a
      noncanonical density matrix for the open system with a finite coupling to the
      heat bath, which deforms the energy shell to effectively modify the conventional
      canonical way. The obtained noncanonical distribution reflects the back action of
      system on the bath and thus depicts the statistical correlations between two
      subsystems by the mutual information as a result of energy conservation. 

PMID- 25615063
TI  - Glassy dynamics in confinement: planar and bulk limits of the mode-coupling
      theory.
AB  - We demonstrate how the matrix-valued mode-coupling theory of the glass transition
      and glassy dynamics in planar confinement converges to the corresponding theory
      for two-dimensional (2D) planar and the three-dimensional bulk liquid, provided
      the wall potential satisfies certain conditions. Since the mode-coupling theory
      relies on the static properties as input, the emergence of a homogeneous limit
      for the matrix-valued intermediate scattering functions is directly connected to
      the convergence of the corresponding static quantities to their conventional
      counterparts. We show that the 2D limit is more subtle than the bulk limit, in
      particular, the in-planar dynamics decouples from the motion perpendicular to the
      walls. We investigate the frozen-in parts of the intermediate scattering function
      in the glass state and find that the limits time t->infinity and effective wall
      separation L->0 do not commute due to the mutual coupling of the residual
      transversal and lateral force kernels. 

PMID- 25615064
TI  - Effect of measurement noise on Granger causality.
AB  - Most of the signals recorded in experiments are inevitably contaminated by
      measurement noise. Hence, it is important to understand the effect of such noise
      on estimating causal relations between such signals. A primary tool for
      estimating causality is Granger causality. Granger causality can be computed by
      modeling the signal using a bivariate autoregressive (AR) process. In this paper,
      we greatly extend the previous analysis of the effect of noise by considering a
      bivariate AR process of general order p. From this analysis, we analytically
      obtain the dependence of Granger causality on various noise-dependent system
      parameters. In particular, we show that measurement noise can lead to spurious
      Granger causality and can suppress true Granger causality. These results are
      verified numerically. Finally, we show how true causality can be recovered
      numerically using the Kalman expectation maximization algorithm. 

PMID- 25615065
TI  - Intermittency and dynamical Lee-Yang zeros of open quantum systems.
AB  - We use high-order cumulants to investigate the Lee-Yang zeros of generating
      functions of dynamical observables in open quantum systems. At long times the
      generating functions take on a large-deviation form with singularities of the
      associated cumulant generating functions-or dynamical free energies-signifying
      phase transitions in the ensemble of dynamical trajectories. We consider a driven
      three-level system as well as the dissipative Ising model. Both systems exhibit
      dynamical intermittency in the statistics of quantum jumps. From the short-time
      behavior of the dynamical Lee-Yang zeros, we identify critical values of the
      counting field which we attribute to the observed intermittency and dynamical
      phase coexistence. Furthermore, for the dissipative Ising model we construct a
      trajectory phase diagram and estimate the value of the transverse field where the
      stationary state changes from being ferromagnetic (inactive) to paramagnetic
      (active). 

PMID- 25615066
TI  - Localization in covariance matrices of coupled heterogenous Ornstein-Uhlenbeck
      processes.
AB  - We define a random-matrix ensemble given by the infinite-time covariance matrices
      of Ornstein-Uhlenbeck processes at different temperatures coupled by a Gaussian
      symmetric matrix. The spectral properties of this ensemble are shown to be in
      qualitative agreement with some stylized facts of financial markets. Through the
      presented model formulas are given for the analysis of heterogeneous time series.
      Furthermore evidence for a localization transition in eigenvectors related to
      small and large eigenvalues in cross-correlations analysis of this model is
      found, and a simple explanation of localization phenomena in financial time
      series is provided. Finally we identify both in our model and in real financial
      data an inverted-bell effect in correlation between localized components and
      their local temperature: high- and low-temperature components are the most
      localized ones. 

PMID- 25615067
TI  - Driven inelastic Maxwell gases.
AB  - We consider the inelastic Maxwell model, which consists of a collection of
      particles that are characterized by only their velocities and evolving through
      binary collisions and external driving. At any instant, a particle is equally
      likely to collide with any of the remaining particles. The system evolves in
      continuous time with mutual collisions and driving taken to be point processes
      with rates tau(c)(-1) and tau(w)(-1), respectively. The mutual collisions
      conserve momentum and are inelastic, with a coefficient of restitution r. The
      velocity change of a particle with velocity v, due to driving, is taken to be
      Deltav=-(1+r(w))v+eta, where r(w)?[-1,1] and eta is Gaussian white noise. For
      r(w)?(0,1], this driving mechanism mimics the collision with a randomly moving
      wall, where r(w) is the coefficient of restitution. Another special limit of this
      driving is the so-called Ornstein-Uhlenbeck process given by dv/dt=-Gammav+eta.
      We show that while the equations for the n-particle velocity distribution
      functions (n=1,2,...) do not close, the joint evolution equations of the variance
      and the two-particle velocity correlation functions close. With the exact formula
      for the variance we find that, for r(w)?-1, the system goes to a steady state.
      Also we obtain the exact tail of the velocity distribution in the steady state.
      On the other hand, for r(w)=-1, the system does not have a steady state.
      Similarly, the system goes to a steady state for the Ornstein-Uhlenbeck driving
      with Gamma?0, whereas for the purely diffusive driving (Gamma=0), the system does
      not have a steady state.

PMID- 25615069
TI  - Crossover from a Kosterlitz-Thouless phase transition to a discontinuous phase
      transition in two-dimensional liquid crystals.
AB  - Liquid crystals in two dimensions do not support long-range nematic order, but a
      quasinematic phase where the orientational correlations decay algebraically is
      possible. The transition from the isotropic to the quasinematic phase can be
      continuous and of the Kosterlitz-Thouless type, or it can be first order. We
      report here on a liquid-crystal model where the nature of the isotropic to
      quasinematic transition can be tuned via a single parameter p in the pair
      potential. For p<p(t), the transition is of the Kosterlitz-Thouless type, while
      for p>p(t), it is first order. Precisely at p=p(t), there is a tricritical point
      where, in addition to the orientational correlations, also the positional
      correlations decay algebraically. The tricritical behavior is analyzed in detail,
      including an accurate estimate of p(t). The results follow from extensive Monte
      Carlo simulations combined with a finite-size scaling analysis. Paramount in the
      analysis is a scheme to facilitate the extrapolation of simulation data in
      parameters that are not necessarily field variables (in this case, the parameter
      p), the details of which are also provided. This scheme provides a simple and
      powerful alternative for situations where standard histogram reweighting cannot
      be applied.

PMID- 25615068
TI  - Time reversal in nonequilibrium thermodynamics.
AB  - The general equation of nonequilibrium reversible-irreversible coupling (GENERIC)
      is studied in light of time-reversal transformation. It is shown that Onsager
      Casimir reciprocal relations are implied by GENERIC in the near-equilibrium
      regime. A general structure which gives the reciprocal relations but which is
      valid also far from equilibrium is identified, and Onsager-Casimir reciprocal
      relations are generalized to far-from-equilibrium regime in this sense. Moreover,
      reversibility and irreversibility are carefully discussed and the results are
      illustrated in Hamiltonian dynamics, classical hydrodynamics, classical
      irreversible thermodynamics, the quantum master equation, and the Boltzmann
      equation. 

PMID- 25615070
TI  - Strong-coupling phases of the anisotropic Kardar-Parisi-Zhang equation.
AB  - We study the anisotropic Kardar-Parisi-Zhang equation using nonperturbative
      renormalization group methods. In contrast to a previous analysis in the weak
      coupling regime, we find the strong-coupling fixed point corresponding to the
      isotropic rough phase to be always locally stable and unaffected by the
      anisotropy even at noninteger dimensions. Apart from the well-known weak-coupling
      and the now well-established isotropic strong-coupling behavior, we find an
      anisotropic strong-coupling fixed point for nonlinear couplings of opposite signs
      at noninteger dimensions. 

PMID- 25615071
TI  - Efficiency at maximum power of a quantum Otto cycle within finite-time or
      irreversible thermodynamics.
AB  - We consider the efficiency at maximum power of a quantum Otto engine, which uses
      a spin or a harmonic system as its working substance and works between two heat
      reservoirs at constant temperatures T(h) and T(c) (<T(h)). Although the behavior
      of spin-1/2 system differs substantially from that of the harmonic system in that
      they obey two typical quantum statistics, the efficiencies at maximum power based
      on these two different kinds of quantum systems are bounded from the upper side
      by the same expression eta(mp)<=eta(+)=eta(C)(2)/[eta(C)-(1-eta(C))ln(1-eta(C))]
      with eta(C)=1-T(c)/T(h) as the Carnot efficiency. This expression eta(mp)
      possesses the same universality of the CA efficiency eta(CA)=1-?(1-eta(C)) at
      small relative temperature difference. Within the context of irreversible
      thermodynamics, we calculate the Onsager coefficients and show that the value of
      eta(CA) is indeed the upper bound of EMP for an Otto engine working in the linear
      response regime.

PMID- 25615072
TI  - Infinite densities for Levy walks.
AB  - Motion of particles in many systems exhibits a mixture between periods of random
      diffusive-like events and ballistic-like motion. In many cases, such systems
      exhibit strong anomalous diffusion, where low-order moments <|x(t)|(q)> with q
      below a critical value q(c) exhibit diffusive scaling while for q>q(c) a
      ballistic scaling emerges. The mixed dynamics constitutes a theoretical challenge
      since it does not fall into a unique category of motion, e.g., the known
      diffusion equations and central limit theorems fail to describe both aspects. In
      this paper we resolve this problem by resorting to the concept of infinite
      density. Using the widely applicable Levy walk model, we find a general
      expression for the corresponding non-normalized density which is fully determined
      by the particles velocity distribution, the anomalous diffusion exponent alpha,
      and the diffusion coefficient K(alpha). We explain how infinite densities play a
      central role in the description of dynamics of a large class of physical
      processes and discuss how they can be evaluated from experimental or numerical
      data.

PMID- 25615073
TI  - Crossover from rotational to stochastic sandpile universality in the random
      rotational sandpile model.
AB  - In the rotational sandpile model, either the clockwise or the anticlockwise
      toppling rule is assigned to all the lattice sites. It has all the features of a
      stochastic sandpile model but belongs to a different universality class than the
      Manna class. A crossover from rotational to Manna universality class is studied
      by constructing a random rotational sandpile model and assigning randomly
      clockwise and anticlockwise rotational toppling rules to the lattice sites. The
      steady state and the respective critical behavior of the present model are found
      to have a strong and continuous dependence on the fraction of the lattice sites
      having the anticlockwise (or clockwise) rotational toppling rule. As the
      anticlockwise and clockwise toppling rules exist in equal proportions, it is
      found that the model reproduces critical behavior of the Manna model. It is then
      further evidence of the existence of the Manna class, in contradiction with some
      recent observations of the nonexistence of the Manna class. 

PMID- 25615074
TI  - Finite-size scaling above the upper critical dimension.
AB  - We present a unified view of finite-size scaling (FSS) in dimension d above the
      upper critical dimension, for both free and periodic boundary conditions. We find
      that the modified FSS proposed some time ago to allow for violation of
      hyperscaling due to a dangerous irrelevant variable applies only to k=0
      fluctuations, and "standard" FSS applies to k?0 fluctuations. Hence the exponent
      eta describing power-law decay of correlations at criticality is unambiguously
      eta=0. With free boundary conditions, the finite-size "shift" is greater than the
      rounding. Nonetheless, using T-T(L), where T(L) is the finite-size pseudocritical
      temperature, rather than T-T(c), as the scaling variable, the data do collapse
      onto a scaling form that includes the behavior both at T(L), where the
      susceptibility chi diverges like L(d/2), and at the bulk T(c), where it diverges
      like L(2). These claims are supported by large-scale simulations on the five
      dimensional Ising model.

PMID- 25615075
TI  - First-passage times, mobile traps, and Hopf bifurcations.
AB  - For a random walk on a confined one-dimensional domain, we consider mean first
      passage times (MFPT) in the presence of a mobile trap. The question we address is
      whether a mobile trap can improve capture times over a stationary trap. We
      consider two scenarios: a randomly moving trap and an oscillating trap. In both
      cases, we find that a stationary trap actually performs better (in terms of
      reducing expected capture time) than a very slowly moving trap; however, a trap
      moving sufficiently fast performs better than a stationary trap. We explicitly
      compute the thresholds that separate the two regimes. In addition, we find a
      surprising relation between the oscillating trap problem and a moving-sink
      problem that describes reduced dynamics of a single spike in a certain regime of
      the Gray-Scott model. Namely, the above-mentioned threshold corresponds precisely
      to a Hopf bifurcation that induces oscillatory motion in the location of the
      spike. We use this correspondence to prove the uniqueness of the Hopf
      bifurcation. 

PMID- 25615076
TI  - Mechanics of anisotropic spring networks.
AB  - We construct and analyze a model for a disordered linear spring network with
      anisotropy. The modeling is motivated by, for example, granular systems, nematic
      elastomers, and ultimately cytoskeletal networks exhibiting some underlying
      anisotropy. The model consists of a triangular lattice with two different bond
      occupation probabilities, p(x) and p(y), for the linear springs. We develop an
      effective medium theory (EMT) to describe the network elasticity as a function of
      p(x) and p(y). We find that the onset of rigidity in the EMT agrees with Maxwell
      constraint counting. We also find beyond linear behavior in the shear and bulk
      modulus as a function of occupation probability in the rigid phase for small
      strains, which differs from the isotropic case. We compare our EMT with numerical
      simulations to find rather good agreement. Finally, we discuss the implications
      of extending the reach of effective medium theory as well as draw connections
      with prior work on both anisotropic and isotropic spring networks.

PMID- 25615077
TI  - Optimization in finite-reservoir finite-time thermodynamics.
AB  - A necessary condition to optimize work output is obtained for general heat
      engines working between two finite-sized heat reservoirs in a given period of
      time tau, with the amount of heat received from the hot reservoir being fixed for
      all possible realizations of the process. It states that T(c)sigma should be a
      constant during the optimized process, where T(c) is the temperature of the cold
      reservoir, which could be time dependent, and sigma[over ] is the entropy
      production rate of the two reservoirs. Further optimizing tau gives the maximum
      time-averaged power output; the corresponding thermodynamical efficiency,
      however, is found to be generally not equal to half of the maximum efficiency due
      to the finiteness of the sizes of two reservoirs. Our results are obtained within
      the framework of Onsager's theory of linear irreversible thermodynamics and under
      the tight-coupling condition. The findings in this work may potentially be
      applied in the optimization of realistic thermodynamical processes.

PMID- 25615078
TI  - Ensemble inequivalence in a mean-field XY model with ferromagnetic and nematic
      couplings.
AB  - We explore ensemble inequivalence in long-range interacting systems by studying
      an XY model of classical spins with ferromagnetic and nematic coupling. We
      demonstrate the inequivalence by mapping the microcanonical phase diagram onto
      the canonical one, and also by doing the inverse mapping. We show that the
      equilibrium phase diagrams within the two ensembles strongly disagree within the
      regions of first-order transitions, exhibiting interesting features like
      temperature jumps. In particular, we discuss the coexistence and forbidden
      regions of different macroscopic states in both the phase diagrams. 

PMID- 25615079
TI  - Angularly anisotropic correlation in granular packings.
AB  - We present an x-ray microtomography study of the three-dimensional structural
      correlations in monodisperse granular packings. By measuring an orientation
      dependent pair correlation function, we find that the local structure shows an
      angularly anisotropic orientation correlation. The correlation is strongest along
      the major axis of the local Minkowski tensor of the Voronoi cell. It turns out
      that this anisotropic correlation is consistent with the existence of some
      locally favored structures. The study suggests the importance of high-order
      structural correlations in random granular packings. 

PMID- 25615080
TI  - Drag-force regimes in granular impact.
AB  - We study the penetration dynamics of a projectile incident normally on a
      substrate comprising of smaller granular particles in three-dimensions using the
      discrete element method. Scaling of the penetration depth is consistent with
      experimental observations for small velocity impacts. Our studies are consistent
      with the observation that the normal or drag force experienced by the penetrating
      grain obeys the generalized Poncelet law, which has been extensively invoked in
      understanding the drag force in the recent experimental data. We find that the
      normal force experienced by the projectile consists of position and kinetic
      energy-dependent pieces. Three different penetration regimes are identified in
      our studies for low-impact velocities. The first two regimes are observed
      immediately after the impact and in the early penetration stage, respectively,
      during which the drag force is seen to depend on the kinetic energy. The depth
      dependence of the drag force becomes significant in the third regime when the
      projectile is moving slowly and is partially immersed in the substrate. These
      regimes relate to the different configurations of the bed: the initial loose
      surface packed state, fluidized bed below the region of impact, and the state
      after the crater formation commences. 

PMID- 25615081
TI  - Numerical investigation of the vertical plunging force of a spherical intruder
      into a prefluidized granular bed.
AB  - The plunging of a large intruder sphere into a prefluidized granular bed with
      various constant velocities and various sphere diameters is investigated using a
      state-of-the-art hybrid discrete particle and immersed boundary method, in which
      both the gas-induced drag force and the contact force exerted on the intruder can
      be investigated separately. We investigate low velocities, where velocity
      dependent effects first begin to appear. The results show a concave-to-convex
      dependence of the plunging force as a function of intruder depth. In the concave
      region the force fits to a power law with an exponent around 1.3, which is in
      good agreement with existing experimental observations. Our simulation results
      further show that the force exerted on the frontal hemisphere of the intruder is
      dominant. At larger intruder velocities, friction with the granular medium causes
      a velocity-dependent drag force. As long as the granular particles have not yet
      closed the gap behind the intruder, this drag force is independent of the actual
      intruder depth. In this regime, the drag force experienced by intruders of
      different diameter moving at different velocities all fall onto a single master
      curve if plotted against the Reynolds number, using a single value for the
      effective viscosity of the granular medium. This master curve corresponds well to
      the Schiller-Naumann correlation for the drag force between a sphere and a
      Newtonian fluid. After the gap behind the intruder has closed, the drag force
      increases not only with velocity but also with depth. We attribute this to the
      effect of increasing hydrostatic particle pressure in the granular medium,
      leading to an increase in effective viscosity. 

PMID- 25615082
TI  - Shear viscosity of a model for confined granular media.
AB  - The shear viscosity in the dilute regime of a model for confined granular matter
      is studied by simulations and kinetic theory. The model consists on projecting
      into two dimensions the motion of vibrofluidized granular matter in shallow boxes
      by modifying the collision rule: besides the restitution coefficient that
      accounts for the energy dissipation, there is a separation velocity that is added
      in each collision in the normal direction. The two mechanisms balance on average,
      producing stationary homogeneous states. Molecular dynamics simulations show that
      in the steady state the distribution function departs from a Maxwellian, with
      cumulants that remain small in the whole range of inelasticities. The shear
      viscosity normalized with stationary temperature presents a clear dependence with
      the inelasticity, taking smaller values compared to the elastic case. A Boltzmann
      like equation is built and analyzed using linear response theory. It is found
      that the predictions show an excellent agreement with the simulations when the
      correct stationary distribution is used but a Maxwellian approximation fails in
      predicting the inelasticity dependence of the viscosity. These results confirm
      that transport coefficients depend strongly on the mechanisms that drive them to
      stationary states. 

PMID- 25615083
TI  - Low-frequency oscillations and convective phenomena in a density-inverted
      vibrofluidized granular system.
AB  - Low-frequency oscillations (LFOs) are thought to play an important role in the
      transition between the Leidenfrost and convective states of a vibrated granular
      bed. This work details the experimental observation of LFOs, which are found to
      be consistently present for a range of driving frequencies and amplitudes, with
      particles of varying material and using containers of differing material
      properties. The experimentally acquired results show a close qualitative and
      quantitative agreement with both theory and simulations across the range of
      parameters tested. Strong agreement between experimental and simulation results
      was also observed when investigating the influence of sidewall dissipation on
      LFOs and vertical density profiles. This paper additionally provides evidence of
      two phenomena present in the Leidenfrost state: a circulatory motion over
      extended time periods in near-crystalline configurations, and a Leidenfrost-like
      state in which the dense upper region displays an unusual inverse thermal
      convection. 

PMID- 25615084
TI  - Flow of granular matter in a silo with multiple exit orifices: jamming to mixing.
AB  - We investigate the mixing characteristics of dry granular material while draining
      down a silo with multiple exit orifices. The mixing in the silo, which otherwise
      consists of noninteracting stagnant and flowing regions, is observed to improve
      significantly when the flow through specific orifices is stopped intermittently.
      This momentary stoppage of flow through the orifice is either controlled manually
      or is chosen by the system itself when the orifice width is small enough to cause
      spontaneous jamming and unjamming. We observe that the overall mixing behavior
      shows a systematic dependence on the frequency of closing and opening of specific
      orifices. In particular, the silo configuration employing random jamming and
      unjamming of any of the orifices shows early evidence of chaotic mixing. When
      operated in a multipass mode, the system exhibits a practical and efficient way
      of mixing particles. 

PMID- 25615085
TI  - Simulation of cohesive fine powders under a plane shear.
AB  - Three-dimensional molecular-dynamics simulations of cohesive dissipative powders
      under a plane shear are performed. We find the various phases depending on the
      dimensionless shear rate and the dissipation rate as well as the density. We also
      find that the shape of clusters depends on the initial condition of velocities of
      particles when the dissipation is large. Our simple stochastic model reproduces
      the non-Gaussian velocity distribution function appearing in the coexistence
      phase of a gas and a plate. 

PMID- 25615086
TI  - Structural characterization of submerged granular packings.
AB  - We consider the impact of the effective gravitational acceleration on
      microstructural properties of granular packings through experimental studies of
      spherical granular materials saturated within fluids of varying density. We
      characterize the local organization of spheres in terms of contact connectivity,
      distribution of the Delaunay free volumes, and the shape factor (parameter of
      nonsphericity) of the Voronoi polygons. The shape factor gives a clear physical
      picture of the competition between less and more ordered domains of particles in
      experimentally obtained packings. As the effective gravity increases, the
      probability distribution of the shape factor becomes narrower and more localized
      around the lowest values of the shape factor corresponding to regular hexagon. It
      is found that curves of the pore distributions are asymmetric with a long tail on
      the right-hand side, which progressively reduces while the effective gravity gets
      stronger for lower densities of interstitial fluid. We show that the distribution
      of local areas (Voronoi cells) broadens with decreasing value of the effective
      gravity due to the formation of lose structures such as large pores and chainlike
      structures (arches or bridges). Our results should be particularly helpful in
      testing the newly developed simulation techniques involving liquid-related forces
      associated with immersed granular particles. 

PMID- 25615087
TI  - Manipulating chiral microswimmers in a channel.
AB  - We numerically simulate the diffusion of overdampd pointlike Janus particles
      along narrow two-dimensional periodically corrugated channels with reflecting
      walls. The self-propulsion velocity of the particle is assumed to rotate subject
      to an intrinsic bias modeled by a torque. Breaking the mirror symmetry of the
      channel with respect to its axis suffices to generate a directed particle flow
      with orientation and magnitude which depend on the channel geometry and the
      particle swimming properties. This means that chiral microswimmers drift
      autonomously along a narrow channel under more general asymmetry conditions than
      previously reported, a property of potential impact on their fabrication and
      technological applications. 

PMID- 25615088
TI  - Absence of red structural color in photonic glasses, bird feathers, and certain
      beetles.
AB  - Colloidal glasses, bird feathers, and beetle scales can all show structural
      colors arising from short-ranged spatial correlations between scattering centers.
      Unlike the structural colors arising from Bragg diffraction in ordered materials
      like opals, the colors of these photonic glasses are independent of orientation,
      owing to their disordered, isotropic microstructures. However, there are few
      examples of photonic glasses with angle-independent red colors in nature, and
      colloidal glasses with particle sizes chosen to yield structural colors in the
      red show weak color saturation. Using scattering theory, we show that the absence
      of angle-independent red color can be explained by the tendency of individual
      particles to backscatter light more strongly in the blue. We discuss how the
      backscattering resonances of individual particles arise from cavity-like modes
      and how they interact with the structural resonances to prevent red. Finally, we
      use the model to develop design rules for colloidal glasses with red, angle
      independent structural colors. 

PMID- 25615089
TI  - Multifractality in dilute magnetorheological fluids under an oscillating magnetic
      field.
AB  - A study of the multifractal characteristics of the structure formed by magnetic
      particles in a dilute magnetorheological fluid is presented. A quasi-two
      dimensional magnetorheological fluid sample is simultaneously subjected to a
      static magnetic field and a sinusoidal magnetic field transverse to each other.
      We analyzed the singularity spectrum f(alpha) and the generalized dimension D(q)
      of the whole structure to characterize the distribution of the aggregates under
      several conditions of particle concentration, magnetic field intensities, and
      liquid viscosity. We also obtained the fractal dimension D(g), calculated from
      the radius of gyration of the chains, to describe the internal distribution of
      the particles. We present a thermodynamic interpretation of the multifractal
      analysis, and based on this, we discussed the characteristics of the structure
      formed by the particles and its relation with previous studies of the average
      chain length. We have found that this method is useful to quantitatively describe
      the structure of magnetorheological fluids, especially in systems with high
      particle concentration where the aggregates are more complex than simple chains
      or columns.

PMID- 25615090
TI  - Gaussian memory in kinematic matrix theory for self-propellers.
AB  - We extend the kinematic matrix ("kinematrix") formalism [Phys. Rev. E 89, 062304
      (2014)], which via simple matrix algebra accesses ensemble properties of self
      propellers influenced by uncorrelated noise, to treat Gaussian correlated noises.
      This extension brings into reach many real-world biological and biomimetic self
      propellers for which inertia is significant. Applying the formalism, we analyze
      in detail ensemble behaviors of a 2D self-propeller with velocity fluctuations
      and orientation evolution driven by an Ornstein-Uhlenbeck process. On the basis
      of exact results, a variety of dynamical regimes determined by the inertial,
      speed-fluctuation, orientational diffusion, and emergent disorientation time
      scales are delineated and discussed.

PMID- 25615091
TI  - Vibrational and structural signatures of the crossover between dense glassy and
      sparse gel-like attractive colloidal packings.
AB  - We investigate the vibrational modes of quasi-two-dimensional disordered
      colloidal packings of hard colloidal spheres with short-range attractions as a
      function of packing fraction. Certain properties of the vibrational density of
      states (vDOS) are shown to correlate with the density and structure of the
      samples (i.e., in sparsely versus densely packed samples). Specifically, a
      crossover from dense glassy to sparse gel-like states is suggested by an excess
      of phonon modes at low frequency and by a variation in the slope of the vDOS with
      frequency at low frequency. This change in phonon mode distribution is
      demonstrated to arise largely from localized vibrations that involve individual
      and/or small clusters of particles with few local bonds. Conventional order
      parameters and void statistics did not exhibit obvious gel-glass signatures as a
      function of volume fraction. These mode behaviors and accompanying structural
      insights offer a potentially new set of indicators for identification of glass
      gel transitions and for assignment of gel-like versus glass-like character to a
      disordered solid material. 

PMID- 25615092
TI  - Existence of a liquid-liquid phase transition in methanol.
AB  - A simple model is constructed to study the phase diagram and thermodynamic
      properties of methanol, which is described as a dimer of an apolar sphere
      mimicking the methyl group and a sphere with core-softened potential as the
      hydroxyl group. Performing classical Monte Carlo simulations, we obtained the
      phase diagram, showing a second critical point between two different liquid
      phases. Evaluating systems with a different number of particles, we extrapolate
      to infinite size in accordance with Ising universality class to obtain bulk
      values for critical temperature, pressure, and density. Strong evidence that the
      structure of the liquid changes upon transition from high- to low-density phase
      was provided. From the experimentally determined hydrogen bond strength and
      length in methanol and water, we propose where the second critical point of
      methanol should be. 

PMID- 25615093
TI  - Active nematic materials with substrate friction.
AB  - Active turbulence in dense active systems is characterized by high vorticity on a
      length scale that is large compared to that of individual entities. We describe
      the properties of active turbulence as momentum propagation is screened by
      frictional damping. As friction is increased, the spacing between the walls in
      the nematic director field decreases as a consequence of the more rapid velocity
      decays. This leads to, first, a regime with more walls and an increased number of
      topological defects, and then to a jammed state in which the walls deliminate
      bands of opposing flow, analogous to the shear bands observed in passive complex
      fluids. 

PMID- 25615094
TI  - Phase transitions and self-organization of Janus disks in two dimensions studied
      by Monte Carlo simulations.
AB  - The phase behavior of Janus disks on a square lattice is studied using the Monte
      Carlo method. A particle is composed of two different parts, A and B. The
      interactions between neighboring particles depend on their orientations. To
      control the strength of the interactions, we use energy parameters characterizing
      AA,BB, and AB contacts. The phase diagrams are estimated. We found two phase
      transitions, namely first-order transitions between colloidal-rich and colloidal
      poor phases, and continuous order-disorder transitions to different ordered
      phases. A variety of ordered structures occurs depending on the relation between
      the energy parameters and on the fluid density. The influence of energy
      parameters on the phase diagram topology and critical parameters is shown. The
      competition between phase transitions and self-organization is discussed. 

PMID- 25615095
TI  - Inferring elastic properties of an fcc crystal from displacement correlations:
      subspace projection and statistical artifacts.
AB  - We compute the effective dispersion and vibrational density of states (DOS) of
      two-dimensional subregions of three-dimensional face-centered-cubic crystals
      using both a direct projection-inversion technique and a Monte Carlo simulation
      based on a common underlying Hamiltonian. We study both a (111) and (100) plane.
      We show that for any given direction of wave vector, both (111) and (100) show an
      anomalous omega(2)~q regime at low q where omega(2) is the energy associated with
      the given mode and q is its wave number. The omega(2)~q scaling should be
      expected to give rise to an anomalous DOS, D(omega), at low omega:
      D(omega)~omega(3) rather than the conventional Debye result: D(omega)~omega(2).
      The DOS for (100) looks to be consistent with D(omega)~omega(3), while (111)
      shows something closer to the conventional Debye result at the smallest
      frequencies. In addition to the direct projection-inversion calculation, we
      perform Monte Carlo simulations to study the effects of finite sampling
      statistics. We show that finite sampling artifacts act as an effective disorder
      and bias D(omega), giving a behavior closer to D(omega)~omega(2) than
      D(omega)~omega(3). These results should have an important impact on the
      interpretation of recent studies of colloidal solids where the two-point
      displacement correlations can be obtained directly in real-space via microscopy.

PMID- 25615096
TI  - Echoes in x-ray speckles track nanometer-scale plastic events in colloidal gels
      under shear.
AB  - We report x-ray photon correlation spectroscopy experiments on a concentrated
      nanocolloidal gel subject to in situ oscillatory shear strain. The strain causes
      periodic echoes in the speckle pattern that lead to peaks in the intensity
      autocorrelation function. Above a threshold strain that is near the first yield
      point of the gel, the peak amplitude decays exponentially with the number of
      shear cycles, signaling irreversible particle rearrangements. The wave-vector
      dependence of the decay rate reveals a power-law distribution in the size of
      regions undergoing shear-induced rearrangement. The gel also displays strain
      softening well below the threshold, indicating a range of strains at which the
      rheology is nonlinear but the microscopic deformations are reversible. 

PMID- 25615097
TI  - Dynamical properties and melting of binary two-dimensional colloidal alloys.
AB  - A two-dimensional (2D) binary colloidal system consisting of interacting dipoles
      is investigated using an analytical approach. Within the harmonic approximation
      we obtain the phonon spectrum of the system as a function of the composition,
      dipole-moment ratio, and mass ratio between the small and big particles. Through
      a systematic analysis of the phonon spectra we are able to determine the
      stability region of the different lattice structures of the colloidal alloys. The
      gaps in the phonon frequency spectrum, the optical frequencies in the long
      wavelength limit, and the sound velocity are discussed as well. Using the
      modified Lindemann criterion and within the harmonic approximation we estimate
      the melting temperature of the sublattice generated by the big particles. 

PMID- 25615098
TI  - Activity-induced collapse and reexpansion of rigid polymers.
AB  - We study the elastic properties of a rigid filament in a bath of self-propelled
      particles. We find that while fully flexible filaments swell monotonically upon
      increasing the strength of the propelling force, rigid filaments soften for
      moderate activities, collapse into metastable hairpins for intermediate
      strengths, and eventually reexpand when the strength of the activity of the
      surrounding fluid is large. This collapse and reexpansion of the filament with
      the bath activity is reminiscent of the behavior observed in polyelectrolytes in
      the presence of different concentrations of multivalent salt. 

PMID- 25615099
TI  - Theory of coherent van der Waals matter.
AB  - We explain in depth the previously proposed theory of the coherent van der Waals
      (cvdW) interaction, the counterpart of van der Waals (vdW) force, emerging in
      spatially coherently fluctuating electromagnetic fields. We show that cvdW driven
      matter is dominated by many-body interactions, which are significantly stronger
      than those found in standard van der Waals (vdW) systems. Remarkably, the leading
      two- and three-body interactions are of the same order with respect to the
      distance (?R(-6)), in contrast to the usually weak vdW three-body effects (?R(
      9)). From a microscopic theory we show that the anisotropic cvdW many-body
      interactions drive the formation of low-dimensional structures such as chains,
      membranes, and vesicles with very unusual, nonlocal properties. In particular,
      cvdW chains display a logarithmically growing stiffness with the chain length,
      while cvdW membranes have a bending modulus growing linearly with their size. We
      argue that the cvdW anisotropic many-body forces cause local cohesion but also a
      negative effective "surface tension." We conclude by deriving the equation of
      state for cvdW materials and propose experiments to test the theory, in
      particular the unusual three-body nature of cvdW.

PMID- 25615100
TI  - Signature of time-dependent hydrodynamic interactions on collective diffusion in
      colloidal monolayers.
AB  - It has been shown recently that the coefficient of collective diffusion in a
      colloidal monolayer is divergent due to the hydrodynamic interactions mediated by
      the ambient fluid in bulk. The analysis is extended to allow for time-dependent
      hydrodynamic interactions. Observational features specific to this time
      dependency are predicted. The possible experimental detection in the dynamics of
      the monolayer is discussed. 

PMID- 25615101
TI  - Invariance of conductivity relaxation under pressure and temperature variations
      at constant conductivity relaxation time in 0.4Ca(NO3)2-0.6KNO3.
AB  - The article reports the dependence of the conductivity relaxation on temperature
      T and pressure P in the canonical ionic glass former 0.4Ca(NO(3))(2)
      0.6KNO(3)(CKN). At constant conductivity relaxation time tau(sigma), the entire
      conductivity relaxation spectra obtained at widely different combinations of T
      and P superpose almost perfectly, and thus it is the ion-ion interaction but not
      thermodynamics that determines the frequency dispersion. Moreover, on vitrifying
      CKN by either elevating P or decreasing T, changes of P or T dependence of
      tau(sigma) at the glass transition pressure P(g) and temperature T(g) are
      observed to occur at the same value, i.e., tau(sigma)(P(g))=tau(sigma)(T(g)),
      indicating that the relation between tau(sigma) and the structural relaxation
      time tau(alpha) is also independent of P and T.

PMID- 25615102
TI  - Cluster perturbation theory for the self-assembly of associating fluids into
      complex structures.
AB  - Wertheim's two-density thermodynamic perturbation theory (TPT) has proven to be
      an indispensable statistical mechanical tool in the description of associating
      fluids with a single association site. TPT was developed to enforce the
      monovalence of the hydrogen bond and only recently has been extended to account
      for divalent association sites. It has been shown through experiment and
      molecular simulation that certain one-site associating fluids can self-assemble
      into complex extended supramolecular structures as a result of multiple bonding
      of association sites. In this paper we reorganize TPT into a form that is more
      easily applied to complex associated structures. The derived theory is general to
      all possible self-assemble structures. We obtain the free energy and bonding
      fractions in a general way in terms of single-cluster partition functions and
      averages. The new formalism removes any reference to graph theory allowing for
      the conceptually straightforward application of the two-density formalism to
      complex self-assembled structures. 

PMID- 25615103
TI  - Local shear stress and its correlation with local volume fraction in concentrated
      non-Brownian suspensions: lattice Boltzmann simulation.
AB  - The local shear stress of non-Brownian suspensions was investigated using the
      lattice Boltzmann method coupled with the smoothed profile method. Previous
      studies have only focused on the bulk rheology of complex fluids because the
      local rheology of complex fluids was not accessible due to technical limitations.
      In this study, the local shear stress of two-dimensional solid particle
      suspensions in Couette flow was investigated with the method of planes to
      correlate non-Newtonian fluid behavior with the structural evolution of
      concentrated particle suspensions. Shear thickening was successfully captured for
      highly concentrated suspensions at high particle Reynolds number, and both the
      local rheology and local structure of the suspensions were analyzed. It was also
      found that the linear correlation between the local particle stress and local
      particle volume fraction was dramatically reduced during shear thickening. These
      results clearly show how the change in local structure of suspensions influences
      the local and bulk rheology of the suspensions. 

PMID- 25615104
TI  - Dynamics of vacancies in two-dimensional Lennard-Jones crystals.
AB  - Vacancies represent an important class of crystallographic defects, and their
      behaviors can be strongly coupled with relevant material properties. In this
      work, we study the dynamics of generic n-point vacancies in two-dimensional
      Lennard-Jones crystals in several thermodynamic states. Simulations reveal the
      spectrum of distinct, size-dependent vacancy dynamics, including the
      nonmonotonously varying diffusive mobilities of one-, two- and three-point
      vacancies, and several healing routines of linear vacancies. Specifically, we
      numerically observe significantly faster diffusion of the two-point vacancy that
      can be attributed to its rotational degree of freedom. The high mobility of the
      two-point vacancies opens the possibility of doping two-point vacancies into
      atomic materials to enhance atomic migration. The rich physics of vacancies
      revealed in this study may have implications in the engineering of defects in
      extensive crystalline materials for desired properties. 

PMID- 25615105
TI  - Evaluation of x-ray Brillouin scattering data.
AB  - Making use of the classical second-moment sum rule, it is possible to convert a
      series of constant-Q x-ray Brillouin scattering scans (Q momentum transfer) into
      a series of constant frequency scans over the measured Q range. The method is
      applied to literature results for the longitudinal phonon dispersion in several
      glass formers. The constant frequency scans are well fitted in terms of a Q
      independent phonon damping depending exclusively on the frequency, in agreement
      with two recent theories of the boson peak. The method allows us to link the x
      ray Brillouin scattering to the diffuse Umklapp scattering from the boson peak
      vibrations at higher momentum transfer on an absolute intensity scale. 

PMID- 25615106
TI  - Nucleation phenomena in an annealed damage model: statistics of times to failure.
AB  - In this paper we investigate the statistical behavior of an annealed continuous
      damage model. For different model variations we study distributions of times to
      failure and compare these results with the classical case of metastable
      nucleation in statistical physics. We show that our model has a tuning parameter,
      related to the degree of damage reversibility, that determines the model's
      behavior. Depending on the value of this parameter, our model exhibits
      statistical behavior either similar to classical reversible nucleation phenomena
      in statistical physics or to an absolutely different type of behavior intrinsic
      to systems with damage. This comparison allows us to investigate possible
      similarities and differences between damage phenomena and reversible nucleation. 

PMID- 25615107
TI  - Skewness in (1+1)-dimensional Kardar-Parisi-Zhang-type growth.
AB  - We use the (1+1)-dimensional Kardar-Parisi-Zhang equation driven by a Gaussian
      white noise and employ the dynamic renormalization-group of Yakhot and Orszag
      without rescaling [J. Sci. Comput. 1, 3 (1986)]. Hence we calculate the second-
      and third-order moments of height distribution using the diagrammatic method in
      the large-scale and long-time limits. The moments so calculated lead to the value
      S=0.3237 for the skewness. This value is comparable with numerical and
      experimental estimates.

PMID- 25615108
TI  - Edge effects on water droplet condensation.
AB  - In this study we investigate the effect of geometrical or thermal discontinuities
      on the growth of water droplets condensing on a cooled substrate. Edges, corners,
      and cooled and noncooled boundaries can have a strong effect on the vapor
      concentration profile and mass diffusion around the drops. In comparison to
      growth in a pattern where droplets have to compete to catch vapor, which results
      in a linear water concentration profile directed perpendicularly to the
      substrate, droplets near discontinuities can get more vapor (outer edges,
      corners), resulting in faster growth or less vapor (inner edges), giving lower
      growth. When the cooling heat flux limits growth instead of mass diffusion
      (substrate with low thermal conductivity, strong heat exchange with air), edge
      effects can be canceled. In certain cases, growth enhancement can reach nearly
      500% on edges or corners. 

PMID- 25615109
TI  - Geometric control of failure behavior in perforated sheets.
AB  - Adding perforations to a continuum sheet allows new modes of deformation, and
      thus modifies its elastic behavior. The failure behavior of such a perforated
      sheet is explored, using a model experimental system: a material containing a one
      dimensional array of rectangular holes. In this model system, a transition in
      failure mode occurs as the spacing and aspect ratio of the holes are varied:
      rapid failure via a running crack is completely replaced by quasistatic failure,
      which proceeds via the breaking of struts at random positions in the array of
      holes. I demonstrate that this transition can be connected to the loss of stress
      enhancement, which occurs as the material geometry is modified. 

PMID- 25615110
TI  - Effective temperature dynamics of shear bands in metallic glasses.
AB  - We study the plastic deformation of bulk metallic glasses with shear
      transformation zone (STZ) theory, a physical model for plasticity in amorphous
      systems, and compare it with experimental data. In STZ theory, plastic
      deformation occurs when localized regions rearrange due to applied stress and the
      density of these regions is determined by a dynamically evolving effective
      disorder temperature. We compare the predictions of STZ theory to experiments
      that explore the low-temperature deformation of Zr-based bulk metallic glasses
      via shear bands at various thermal temperatures and strain rates. By following
      the evolution of effective temperature with time, strain rate, and temperature
      through a series of approximate and numerical solutions to the STZ equations, we
      successfully model a suite of experimentally observed phenomena, including shear
      band aging as apparent from slide-hold-slide tests, a temperature-dependent
      steady-state flow stress, and a strain-rate- and temperature-dependent transition
      from stick-slip (serrated flow) to steady-sliding (nonserrated flow). We find
      that STZ theory quantitatively matches the observed experimental data and
      provides a framework for relating the experimentally measured energy scales to
      different types of atomic rearrangements. 

PMID- 25615111
TI  - Tearing of thin sheets: cracks interacting through an elastic ridge.
AB  - We study the interaction between two cracks propagating quasistatically during
      the tearing of a thin brittle sheet. We show that the cracks attract each other
      following a path described by a power law resulting from the competition between
      elastic and fracture energies. The power law exponent (8/11) is in close
      agreement with experiments. We also show that a second (asymptotic) regime, with
      an exponent of 9/8, emerges for small distances between the two crack tips due to
      the finite transverse curvature of the elastic ridge joining them. 

PMID- 25615112
TI  - Buoyancy-induced on-the-spot mixing in droplets evaporating on nonwetting
      surfaces.
AB  - We investigate hitherto-unexplored flow characteristics inside a sessile droplet
      evaporating on heated hydrophobic and superhydrophobic surfaces and propose the
      use of evaporation-induced flow as a means to promote efficient "on-the-spot"
      mixing in microliter-sized droplets. Evaporative cooling at the droplet interface
      establishes a temperature gradient that induces buoyancy-driven convection inside
      the droplet. An asymmetric single-roll flow pattern is observed on the
      superhydrophobic substrate, in stark contrast with the axisymmetric toroidal flow
      pattern that develops on the hydrophobic substrate. The difference in flow
      patterns is attributed to the larger height-to-diameter aspect ratio of the
      droplet (of the same volume) on the superhydrophobic substrate, which dictates a
      single asymmetric vortex as the stable buoyancy-induced convection mode. A
      scaling analysis relates the observed velocities inside the droplet to the
      Rayleigh number. On account of the difference in flow patterns, Rayleigh numbers,
      and the reduced solid-liquid contact area, the flow velocity is an order of
      magnitude higher in droplets evaporating on a superhydrophobic substrate as
      compared to hydrophobic substrates. Flow velocities in all cases are shown to
      increase with substrate temperature and droplet size: The characteristic time
      required for mixing of a dye in an evaporating sessile droplet is reduced by ~8
      times on a superhydrophobic surface when the substrate temperature is increased
      from 40 to 60  degrees C. The mixing rate is ~15 times faster on the
      superhydrophobic substrate compared to the hydrophobic surface maintained at the
      same temperature of 60  degrees C.

PMID- 25615113
TI  - Manifold configurations of the director field formed by topological defects in
      free and confined geometry in smectic films.
AB  - We study the topology of the c-director field near topological defects with point
      core and with a droplet in the core of the defect in nonpolar smectic-C and
      ferroelectric smectic-C* freestanding films using polarized optical microscopy.
      Free and confined geometry of topological defects and droplets with strong outer
      boundary condition are compared. The c-director field can be remarkably different
      around a point defect and a droplet with the same topological charge S=+1. In
      ferroelectric films, splay deformation of the c-director transforms into bend
      deformation after droplet nucleation. Heating a ferroelectric film with an S=+1
      droplet leads to a dramatic change of the c-director topology from bend to splay.
      In confined geometry we found spiral structures in which the c-director has
      opposite direction of rotation along the inner and outer boundaries of the
      island. Our observations are discussed on the basis of theories taking into
      account both the influence of polarity and of confined geometry on elasticity and
      topology of the c-director field. 

PMID- 25615114
TI  - Periodic dynamics, localization metastability, and elastic interaction of
      colloidal particles with confining surfaces and helicoidal structure of
      cholesteric liquid crystals.
AB  - Nematic and cholesteric liquid crystals are three-dimensional fluids that possess
      long-range orientational ordering and can support both topological defects and
      chiral superstructures. Implications of this ordering remain unexplored even for
      simple dynamic processes such as the ones found in so-called "fall experiments,"
      or motion of a spherical inclusion under the effects of gravity. Here we show
      that elastic and surface anchoring interactions prompt periodic dynamics of
      colloidal microparticles in confined cholesterics when gravity acts along the
      helical axis. We explore elastic interactions between colloidal microparticles
      and confining surfaces as well as with an aligned ground-state helical structure
      of cholesterics for different sizes of spheres relative to the cholesteric pitch,
      demonstrating unexpected departures from Stokes-like behavior at very low
      Reynolds numbers. We characterize metastable localization of microspheres under
      the effects of elastic and surface anchoring periodic potential landscapes seen
      by moving spheres, demonstrating the important roles played by anchoring memory,
      confinement, and topological defect transformation. These experimental findings
      are consistent with the results of numerical modeling performed through
      minimizing the total free energy due to colloidal inclusions at different
      locations along the helical axis and with respect to the confining substrates. A
      potential application emerging from this work is colloidal sorting based on
      particle shapes and sizes. 

PMID- 25615115
TI  - Director reorientation in a nematic liquid crystal with a photosensitive layer.
AB  - We use a molecular-motor model previously proposed for a nematic cell with an azo
      dye monolayer to calculate the director orientation when light is normally
      impinged on the cell. We consider an initial planar configuration for which one
      of the surrounding plates, which we call the reference plate, is submitted to a
      hard-anchoring boundary condition. The other confining plate has a coating
      monolayer of azo-dye molecules such that the change of the orientation of azo-dye
      isomers, due to light, causes changes in the nematic director. The boundary
      conditions on both plates along with the optical field determine the director
      configuration in the bulk. The existence of periodic solutions for the density of
      isomers in trans and cis states, corresponding to weak optical fields, has been
      discussed in the literature. Using a similar approach, we find an approximate
      expression for the density of isomers, written in terms of the director angle,
      which allows us to close the equation for the director configuration on the
      boundary having a photosensitive plate. We decouple the director's angle and the
      isomer densities by assuming extremely different temporal time scales between
      them. We show for a given sample that switching times inversely depend on the
      trans-cis transition rate of photoexcitation whereas relaxation times do not
      depend on it. On the other hand, switching and relaxation times linearly depend
      on effective surface viscosity values. Our model allows us to estimate surface
      viscosity values. 

PMID- 25615116
TI  - Nanosecond electro-optics of a nematic liquid crystal with negative dielectric
      anisotropy.
AB  - We study a nanosecond electro-optic response of a nematic liquid crystal in a
      geometry where an applied electric field E modifies the tensor order parameter
      but does not change the orientation of the optic axis (director N ). We use a
      nematic with negative dielectric anisotropy with the electric field applied
      perpendicularly to N . The field changes the dielectric tensor at optical
      frequencies (optic tensor) due to the following mechanisms: (a) nanosecond
      creation of the biaxial orientational order, (b) uniaxial modification of the
      orientational order that occurs over time scales of tens of nanoseconds, and (c)
      the quenching of director fluctuations with a wide range of characteristic times
      up to milliseconds. We develop a model to describe the dynamics of all three
      mechanisms. We design the experimental conditions to selectively suppress the
      contributions from the quenching of director fluctuations (c) and from the
      biaxial order effect (a) and thus, separate the contributions of the three
      mechanisms in the electro-optic response. As a result, the experimental data can
      be well fitted with the model parameters. The analysis provides a rather detailed
      physical picture of how the liquid crystal responds to a strong electric field on
      a time scale of nanoseconds. The paper provides a useful guidance in the current
      search for the biaxial nematic phase. Namely, the temperature dependence of the
      biaxial susceptibility allows one to estimate the temperature of the potential
      uniaxial-to-biaxial phase transition. An analysis of the quenching of director
      fluctuations indicates that on a time scale of nanoseconds, the classic model
      with constant viscoelastic material parameters might reach its limit of validity.
      The effect of nanosecond electric modification of the order parameter can be used
      in applications in which one needs to achieve ultrafast (nanosecond) changes in
      optical characteristics, such as birefringence.

PMID- 25615117
TI  - Multiscale models of colloidal dispersion of particles in nematic liquid
      crystals.
AB  - We use homogenization theory to develop a multiscale model of colloidal
      dispersion of particles in nematic liquid crystals under weak-anchoring
      conditions. We validate the model by comparing it with simulations by using the
      Landau-de Gennes free energy and show that the agreement is excellent. We then
      use the multiscale model to study the effect that particle anisotropy has on the
      liquid crystal: spherically symmetric particles always reduce the effective
      elastic constant. Asymmetric particles introduce an effective alignment field
      that can increase the Fredericks threshold and decrease the switch-off time. 

PMID- 25615118
TI  - Calculation of the absolute free energy of a smectic-A phase.
AB  - In this paper, we provide a scheme to compute the absolute free energy of a
      smectic-A phase via the "indirect method." The state of interest is connected
      through a three-step reversible path to a reference state. This state consists of
      a low-density layer of rods coupled to two external fields maintaining these rods
      close to the layer's plane and oriented preferably normal to the layer. The low
      density free energy of the reference state can be computed on the basis of the
      relevant second virial coefficients between two rods coupled to the two external
      fields. We apply this technique to the Gay-Berne potential for calamitics with a
      parameter set leading to stable isotropic (I), nematic (N), smectic-A (SmA), and
      crystal (Cr) phases. We locate the I-SmA phase transition at low pressure and the
      sequence of phase transitions I-N-SmA along higher-pressure isobars and we
      establish the location of the I-N-SmA triple point. Close to this triple point,
      we show that the N-SmA transition is clearly first order. Our results are
      compared to the coexistence lines of the approximate phase diagram elucidated by
      de Miguel et al. [J. Chem. Phys. 121, 11183 (2004)] established through the
      direct observation of the sequence of phase transitions occurring along isobars
      under heating or cooling sequences of runs. Finally, we discuss the potential of
      our technique in studying similar transitions observed on layered phases under
      confinement.

PMID- 25615119
TI  - Electrically induced deformation in chiral smectic elastomers with different
      domain structures.
AB  - Electrical actuation is investigated in two kinds of chiral smectic liquid
      crystal elastomers (LCEs) with different domain structures LCE1 and LCE2: The
      latter is better than the former in orientational order. Tracking fluorescent
      beads dispersed on the samples enables us to measure the two-dimensional strain
      tensors in ferroelectric elastomer films. It turns out that the electric-field
      induced strain is polarity dependent and the type of molecular orientation
      responsible for the strain is specified. In LCE1 the shear strain is dominant,
      whereas in LCE2 it is comparable to the elongation strain, which is explained by
      the rotation of the principal axes. The essential differences of the two
      elastomers are observed in the eigenvalues of the strain tensors. The absolute
      values for LCE1 are larger than those for LCE2. The difference is discussed on
      the basis of the domain structures. 

PMID- 25615120
TI  - Monte Carlo simulations on thermodynamic and conformational properties of
      catenated double-ring copolymers.
AB  - The thermodynamic and conformational properties of catenated double-ring A-B
      copolymer melts are investigated through lattice Monte Carlo simulations. The
      topological constraint on the catenated copolymers is shown to suppress demixing
      of A and B monomers. This action results in their order-to-disorder transition
      (ODT) at an increased segregation level and the lamellae below ODT with reduced
      order, when compared to diblock copolymers of linear or single-ring topology. The
      A and B rings are pulled closer by catenation in the copolymer, which leads to
      its smaller gyration radius, lamellar domain spacing, and distance between mass
      centers of the two rings than for the diblock copolymers. With increasing
      segregation tendencies, the gyration radii of the A rings of the catenated
      copolymers stretch along the direction normal to lamellae, while the A-block
      conformations of the single-ring copolymers change their shapes from ellipsoid to
      sphere. 

PMID- 25615121
TI  - Confined polymers in the extended de Gennes regime.
AB  - We show that the problem of describing the conformations of a semiflexible
      polymer confined to a channel can be mapped onto an exactly solvable model in the
      so-called extended de Gennes regime. This regime (where the polymer is neither
      weakly nor strongly confined) has recently been intensively studied
      experimentally and by means of computer simulations. The exact solution predicts
      precisely how the conformational fluctuations depend upon the channel width and
      upon the microscopic parameters characterizing the physical properties of the
      polymer. 

PMID- 25615122
TI  - Accuracy of the blob model for single flexible polymers inside nanoslits that are
      a few monomer sizes wide.
AB  - The de Gennes' blob model is extensively used in different problems of polymer
      physics. This model is theoretically applicable when the number of monomers
      inside each blob is large enough. For confined flexible polymers, this requires
      the confining geometry to be much larger than the monomer size. In this paper,
      the opposite limit of polymer in nanoslits with one to several monomers width is
      studied, using molecular dynamics simulations. Extension of the polymer inside
      nanoslits, confinement force on the plates, and the effective spring constant of
      the confined polymer are investigated. Despite the theoretical limitations of the
      blob model, the simulation results are explained with the blob model very well.
      The agreement is observed for the static properties and the dynamic spring
      constant of the polymer. A theoretical description of the conditions under which
      the dynamic spring constant of the polymer is independent of the small number of
      monomers inside blobs is given. Our results on the limit of applicability of the
      blob model can be useful in the design of nanotechnology devices. 

PMID- 25615123
TI  - Lagrangian approach to understanding the origin of the gill-kinematics switch in
      mayfly nymphs.
AB  - The mayfly nymph breathes under water through an oscillating array of plate
      shaped tracheal gills. As the nymph grows, the kinematics of these gills change
      abruptly from rowing to flapping. The classical fluid dynamics approach to
      consider the mayfly nymph as a pumping device fails in giving clear reasons for
      this switch. In order to shed some light on this switch between the two distinct
      kinematics, we analyze the problem under a Lagrangian viewpoint. We consider that
      a good Lagrangian transport that effectively distributes and stirs water and
      dissolved oxygen between and around the gills is the main goal of the gill
      motion. Using this Lagrangian approach, we are able to provide possible reasons
      behind the observed switch from rowing to flapping. More precisely, we conduct a
      series of in silico mayfly nymph experiments, where body shape, as well as gill
      shapes, structures, and kinematics are matched to those from in vivo. In this
      paper, we show both qualitatively and quantitatively how the change of kinematics
      enables better attraction, confinement, and stirring of water charged of
      dissolved oxygen inside the gills area. We reveal the attracting barriers to
      transport, i.e., attracting Lagrangian coherent structures, that form the
      transport skeleton between and around the gills. In addition, we quantify how
      well the fluid particles are stirred inside the gills area, which by extension
      leads us to conclude that it will increase the proneness of molecules of
      dissolved oxygen to be close enough to the gills for extraction. 

PMID- 25615124
TI  - Spontaneous formation of large clusters in a lattice gas above the critical
      point.
AB  - We consider clustering of particles in the lattice gas model above the critical
      point. We find the probability for large density fluctuations over scales much
      larger than the correlation length. This fundamental problem is of interest in
      various biological contexts such as quorum sensing and clustering of motile,
      adhesive, cancer cells. In the latter case, it may give a clue to the problem of
      growth of recurrent tumors. We develop a formalism for the analysis of this rare
      event employing a phenomenological master equation and measuring the transition
      rates in numerical simulations. The spontaneous clustering is treated in the
      framework of the eikonal approximation to the master equation. 

PMID- 25615125
TI  - Biphasic character of ribosomal translocation and non-Michaelis-Menten kinetics
      of translation.
AB  - We study theoretically the kinetics of mRNA translocation in the wild-type (WT)
      Escherichia coli ribosome, which is composed of a small 30S and large 50S
      subunit, and the ribosomes with mutations to some intersubunit bridges such as
      B1a, B4, B7a, and B8. The theoretical results reproduce well the available in
      vitro experimental data on the biphasic kinetics of the forward mRNA
      translocation catalyzed by elongation factor G (EF-G) hydrolyzing GTP, which can
      be best fit by the sum of two exponentials, and the monophasic kinetics of the
      spontaneous reverse mRNA translocation in the absence of the elongation factor,
      which can be best fit by a single-exponential function, in both the WT and mutant
      ribosomes. We show that both the mutation-induced increase in the maximal rate of
      the slow phase for the forward mRNA translocation and that in the rate of the
      spontaneous reverse mRNA translocation result from a reduction in the intrinsic
      energy barrier to resist the rotational movements between the two subunits,
      giving the same degree of increase in the two rates. The mutation-induced
      increase in the maximal rate of the fast phase for the forward mRNA translocation
      results mainly from the increase in the rate of the ribosomal unlocking, a
      conformational change in the ribosome that widens the mRNA channel for the mRNA
      translocation to take place, which could be partly due to the effect of the
      mutation on the intrasubunit 30S head rotation. Moreover, we study the
      translation rate of the WT and mutant ribosomes. It is shown that the translation
      rate versus the concentration of EF-G-GTP does not follow the Michaelis-Menten
      (MM) kinetics, which is in sharp contrast to the general property of other
      enzymes that the rate of the enzymatic reaction versus the concentration of a
      substrate follows the MM kinetics. The physical origin of this non-MM kinetics
      for the ribosome is revealed. 

PMID- 25615126
TI  - Fluctuations and information filtering in coupled populations of spiking neurons
      with adaptation.
AB  - Finite-sized populations of spiking elements are fundamental to brain function
      but also are used in many areas of physics. Here we present a theory of the
      dynamics of finite-sized populations of spiking units, based on a quasirenewal
      description of neurons with adaptation. We derive an integral equation with
      colored noise that governs the stochastic dynamics of the population activity in
      response to time-dependent stimulation and calculate the spectral density in the
      asynchronous state. We show that systems of coupled populations with adaptation
      can generate a frequency band in which sensory information is preferentially
      encoded. The theory is applicable to fully as well as randomly connected networks
      and to leaky integrate-and-fire as well as to generalized spiking neurons with
      adaptation on multiple time scales. 

PMID- 25615127
TI  - Early warning signals of desertification transitions in semiarid ecosystems.
AB  - The identification of early warning signals for regime shifts in ecosystems is of
      crucial importance given their impact in terms of economic and social effects. We
      present here the results of a theoretical study on the desertification transition
      in semiarid ecosystems under external stress. We performed numerical simulations
      based on a stochastic cellular automaton model, and we studied the dynamics of
      the vegetation clusters in terms of percolation theory, assumed as an effective
      tool for analyzing the geometrical properties of the clusters. Focusing on the
      role played by the strength of external stresses, measured by the mortality rate
      m, we followed the progressive degradation of the ecosystem for increasing m,
      identifying different stages: first, the fragmentation transition occurring at
      relatively low values of m, then the desertification transition at higher
      mortality rates, and finally the full desertification transition corresponding to
      the extinction of the vegetation and the almost complete degradation of the soil,
      attained at the maximum value of m. For each transition we calculated the
      spanning probabilities as functions of m and the percolation thresholds according
      to different spanning criteria. The identification of the different thresholds is
      proposed as an useful tool for monitoring the increasing degradation of real
      world finite-size systems. Moreover, we studied the time fluctuations of the
      sizes of the biggest clusters of vegetated and nonvegetated cells over the entire
      range of mortality values. The change of sign in the skewness of the size
      distributions, occurring at the fragmentation threshold for the biggest
      vegetation cluster and at the desertification threshold for the nonvegetated
      cluster, offers new early warning signals for desertification. Other new and
      robust indicators are given by the maxima of the root-mean-square deviation of
      the distributions, which are attained respectively inside the fragmentation
      interval, for the vegetated biggest cluster, and inside the desertification
      interval, for the nonvegetated cluster. 

PMID- 25615128
TI  - Identifying delayed directional couplings with symbolic transfer entropy.
AB  - We propose a straightforward extension of symbolic transfer entropy to enable the
      investigation of delayed directional relationships between coupled dynamical
      systems from time series. Analyzing time series from chaotic model systems, we
      demonstrate the applicability and limitations of our approach. Our findings
      obtained from applying our method to infer delayed directed interactions in the
      human epileptic brain underline the importance of our approach for improving the
      construction of functional network structures from data. 

PMID- 25615129
TI  - Theoretical model for optical properties of porphyrin.
AB  - We propose a simple model to interpret the optical absorption spectra of
      porphyrin in different solvents. Our model successfully explains the decrease in
      the intensity of optical absorption at maxima of increased wavelengths. We also
      prove the dependence of the intensity and peak positions in the absorption
      spectra on the environment. The nature of the Soret band is supposed to derive
      from pi plasmon. Our theoretical calculations are consistent with previous
      experimental studies. 

PMID- 25615130
TI  - Time delay can facilitate coherence in self-driven interacting-particle systems.
AB  - Directional switching in a self-propelled particle model with delayed
      interactions is investigated. It is shown that the average switching time is an
      increasing function of time delay. The presented results are applied to studying
      collective animal behavior. It is argued that self-propelled particle models with
      time delays can explain the state-dependent diffusion coefficient measured in
      experiments with locust groups. The theory is further generalized to
      heterogeneous groups where each individual can respond to its environment with a
      different time delay. 

PMID- 25615131
TI  - Multiple-time-scale framework for understanding the progression of Parkinson's
      disease.
AB  - Parkinson's disease is marked by neurodegenerative processes that affect the
      pattern of discharge of basal ganglia neurons. The main features observed in the
      parkinsonian globus pallidus pars interna (GPi), a subdomain of the basal ganglia
      that is involved in the regulation of voluntary movement, are pathologically
      increased and synchronized neuronal activity. How these changes affect the
      implemented neuronal code is not well understood. Our experimental temporal
      structure-function analysis shows that in parkinsonian animals the rate-coding
      window of GPi neurons needed for the proper performance of voluntary actions is
      reduced. The model of the GPi network that we develop and discuss here reveals
      indeed that the size of the rate-coding window shrinks as the network activity
      increases and is expanded if the coupling strength among the neurons is
      increased. This leads to the novel interpretation that the pathological neuronal
      synchronization in Parkinson's disease in the GPi is the result of a collective
      attempt to counterbalance the shrinking of the rate-coding window due to
      increased activity in GPi neurons. 

PMID- 25615132
TI  - Dynamics of random neural networks with bistable units.
AB  - We construct and analyze a rate-based neural network model in which self
      interacting units represent clusters of neurons with strong local connectivity
      and random interunit connections reflect long-range interactions. When
      sufficiently strong, the self-interactions make the individual units bistable.
      Simulation results, mean-field calculations, and stability analysis reveal the
      different dynamic regimes of this network and identify the locations in parameter
      space of its phase transitions. We identify an interesting dynamical regime
      exhibiting transient but long-lived chaotic activity that combines features of
      chaotic and multiple fixed-point attractors. 

PMID- 25615133
TI  - Effective diffusion of confined active Brownian swimmers.
AB  - We theoretically find the effect of confinement and thermal fluctuations on the
      diffusivity of a spherical active swimmer moving inside a two-dimensional narrow
      cavity of general shape. The explicit formulas for the effective diffusion
      coefficient of a swimmer moving inside two particular cavities are presented. We
      also compare our analytical results with Brownian dynamics simulations and we
      obtain excellent agreement. 

PMID- 25615134
TI  - Energy transfer in molecular devices.
AB  - Protein machines often exhibit long-range interplay between different sites in
      order to achieve their biological tasks. We investigate and characterize the
      nonlinear energy localization and the basic mechanisms of energy transfer in
      protein devices. By studying two different model protein machines, with different
      biological functions, we show that genuinely nonlinear phenomena are responsible
      for energy transport between the different machine sites involved in the
      biological functions. The energy transfer turns out to be extremely efficient
      from an energetic point of view: by changing the energy initially provided to the
      model device, we identify a well defined range of energies where the time for the
      energy transport to occur is minimal and the amount of transferred energy is a
      maximum. Furthermore, by introducing an implicit solvent, we show that the energy
      is localized on the internal residues of the protein structure, thus minimizing
      the dissipation. 

PMID- 25615135
TI  - Two-dimensional convex-molecule fluid model for surface adsorption of proteins:
      effect of soft interaction on adsorption equilibria.
AB  - Adsorption of proteins on membrane surfaces plays an important role in cell
      biological processes. In this work, we develop a two-dimensional fluid model for
      proteins. The protein molecules have been modeled as two-dimensional convex and
      soft particles. The Lennard-Jones potential for circular particles and Kihara
      (12,6) potential for elliptical particles with hard core have been used to model
      pairwise intermolecular interactions. The equation of state of the fluid model
      has been derived using Weeks-Chandler-Andersen decomposition and it involves
      three parameters, an attraction, a repulsion, and a size parameter, which depend
      on the shape and core size of the molecules. For validation of the model, a two
      dimensional molecular dynamics simulation has been performed. Finally, the model
      has been applied to study the adsorption of proteins on a flat membrane. In
      comparison with the existing model of hard and convex particles for protein
      adsorption, our model predicts a higher packing fraction for the adsorption
      equilibria. Although the present work is based on Lennard-Jones-type interaction,
      it can be extended for other specific soft interactions between convex molecules.
      Thus the model has general applicability for any other two-dimensional adsorption
      systems of molecules with soft interaction. 

PMID- 25615136
TI  - Quasicritical brain dynamics on a nonequilibrium Widom line.
AB  - Is the brain really operating at a critical point? We study the nonequilibrium
      properties of a neural network which models the dynamics of the neocortex and
      argue for optimal quasicritical dynamics on the Widom line where the correlation
      length and information transmission are optimized. We simulate the network and
      introduce an analytical mean-field approximation, characterize the nonequilibrium
      phase transitions, and present a nonequilibrium phase diagram, which shows that
      in addition to an ordered and disordered phase, the system exhibits a
      "quasiperiodic" phase corresponding to synchronous activity in simulations, which
      may be related to the pathological synchronization associated with epilepsy. 

PMID- 25615137
TI  - Structural evolution of proteinlike heteropolymers.
AB  - The biological function of a protein often depends on the formation of an ordered
      structure in order to support a smaller, chemically active configuration of amino
      acids against thermal fluctuations. Here we explore the development of proteins
      evolving to satisfy this requirement using an off-lattice polymer model in which
      monomers interact as low resolution amino acids. To evolve the model, we
      construct a Markov process in which sequences are subjected to random
      replacements, insertions, and deletions and are selected to recover a predefined
      minimum number of solid-ordered monomers using the Lindemann melting criterion.
      We show that polymers generated by this process consistently fold into soluble,
      ordered globules of similar length and complexity to small protein motifs. To
      compare the evolution of the globules with proteins, we analyze the statistics of
      amino acid replacements, the dependence of site mutation rates on solvent
      exposure, and the dependence of structural distance on sequence distance for
      homologous alignments. Despite the simplicity of the model, the results display a
      surprisingly close correspondence with protein data. 

PMID- 25615138
TI  - Hybrid modeling of tumor-induced angiogenesis.
AB  - When modeling of tumor-driven angiogenesis, a major source of analytical and
      computational complexity is the strong coupling between the kinetic parameters of
      the relevant stochastic branching-and-growth of the capillary network, and the
      family of interacting underlying fields. To reduce this complexity, we take
      advantage of the system intrinsic multiscale structure: we describe the
      stochastic dynamics of the cells at the vessel tip at their natural mesoscale,
      whereas we describe the deterministic dynamics of the underlying fields at a
      larger macroscale. Here, we set up a conceptual stochastic model including
      branching, elongation, and anastomosis of vessels and derive a mean field
      approximation for their densities. This leads to a deterministic integropartial
      differential system that describes the formation of the stochastic vessel
      network. We discuss the proper capillary injecting boundary conditions and
      include the results of relevant numerical simulations. 

PMID- 25615139
TI  - Peierls-Nabarro barrier and protein loop propagation.
AB  - When a self-localized quasiparticle excitation propagates along a discrete one
      dimensional lattice, it becomes subject to a dissipation that converts the
      kinetic energy into lattice vibrations. Eventually the kinetic energy no longer
      enables the excitation to cross over the minimum energy barrier between
      neighboring sites, and the excitation becomes localized within a lattice cell. In
      the case of a protein, the lattice structure consists of the C(alpha) backbone.
      The self-localized quasiparticle excitation is the elemental building block of
      loops. It can be modeled by a kink that solves a variant of the discrete
      nonlinear Schrodinger equation. We study the propagation of such a kink in the
      case of the protein G related albumin-binding domain, using the united residue
      coarse-grained molecular-dynamics force field. We estimate the height of the
      energy barriers that the kink needs to cross over in order to propagate along the
      backbone lattice. We analyze how these barriers give rise to both stresses and
      reliefs, which control the kink movement. For this, we deform a natively folded
      protein structure by parallel translating the kink along the backbone away from
      its native position. We release the transposed kink, and we follow how it
      propagates along the backbone toward the native location. We observe that the
      dissipative forces that are exerted on the kink by the various energy barriers
      have a pivotal role in determining how a protein folds toward its native state.

PMID- 25615140
TI  - Branching influences force-velocity curves and length fluctuations in actin
      networks.
AB  - We investigate collective dynamics of branched actin networks growing against a
      rigid movable wall constrained by a resistive force. Computing the force velocity
      relations, we show that the stall force of such networks depends not only on the
      average number of filaments touching the wall, but also on the amount of
      fluctuation of the leading edge of the network. These differences arise due to
      differences in the network architecture, namely, distance between two adjacent
      branching points and the initial distance of the starting filament from the wall,
      with their relative magnitudes influencing the nature of the force velocity
      curves (convex versus concave). We also show that the introduction of branching
      results in nonmonotonic diffusion constant, a quantity that measures the growth
      in length fluctuation of the leading edge of the network, as a function of
      externally applied force. Together our results demonstrate how the collective
      dynamics of a branched network differs from that of a parallel filament network. 

PMID- 25615141
TI  - Unzipping DNA by a periodic force: hysteresis loop area and its scaling.
AB  - Using Monte Carlo simulations, we study the hysteresis in the unzipping of double
      stranded DNA whose ends are subjected to a time-dependent periodic force with
      frequency (omega) and amplitude (G). For the static force, i.e., omega->0, the
      DNA is in equilibrium with no hysteresis. On increasing omega, the area of the
      hysteresis loop initially increases and becomes maximum at frequency omega*(G),
      which depends on the force amplitude G. If the frequency is increased further, we
      find that for lower amplitudes the loop area decreases monotonically to zero, but
      for higher amplitudes it has an oscillatory component. The height of subsequent
      peaks decreases, and finally the loop area becomes zero at very high frequencies.
      The number of peaks depends on the length of the DNA. We give a simple analysis
      to estimate the frequencies at which maxima and minima occur in the loop area. We
      find that the area of the hysteresis loop scales as 1/omega in the high-frequency
      regime, whereas it scales as G(alpha)omega(beta) with exponents alpha=1 and
      beta=5/4 at low frequencies. The values of the exponents alpha and beta are
      different from the exponents reported earlier based on the hysteresis of small
      hairpins.

PMID- 25615142
TI  - Simple, distance-dependent formulation of the Watts-Strogatz model for directed
      and undirected small-world networks.
AB  - Small-world networks-complex networks characterized by a combination of high
      clustering and short path lengths-are widely studied using the paradigmatic model
      of Watts and Strogatz (WS). Although the WS model is already quite minimal and
      intuitive, we describe an alternative formulation of the WS model in terms of a
      distance-dependent probability of connection that further simplifies, both
      practically and theoretically, the generation of directed and undirected WS-type
      small-world networks. In addition to highlighting an essential feature of the WS
      model that has previously been overlooked, namely the equivalence to a simple
      distance-dependent model, this alternative formulation makes it possible to
      derive exact expressions for quantities such as the degree and motif
      distributions and global clustering coefficient for both directed and undirected
      networks in terms of model parameters. 

PMID- 25615143
TI  - Spectrum-based estimators of the bivariate Hurst exponent.
AB  - We discuss two alternate spectrum-based estimators of the bivariate Hurst
      exponent in the power-law cross-correlations setting, the cross-periodogram and
      local X-Whittle estimators, as generalizations of their univariate counterparts.
      As the spectrum-based estimators are dependent on a part of the spectrum taken
      into consideration during estimation, a simulation study showing performance of
      the estimators under varying bandwidth parameter as well as correlation between
      processes and their specification is provided as well. These estimators are less
      biased than the already existent averaged periodogram estimator, which, however,
      has slightly lower variance. The spectrum-based estimators can serve as a good
      complement to the popular time domain estimators. 

PMID- 25615144
TI  - Diversity of multilayer networks and its impact on collaborating epidemics.
AB  - Interacting epidemics on diverse multilayer networks are increasingly important
      in modeling and analyzing the diffusion processes of real complex systems. A
      viral agent spreading on one layer of a multilayer network can interact with its
      counterparts by promoting (cooperative interaction), suppressing (competitive
      interaction), or inducing (collaborating interaction) its diffusion on other
      layers. Collaborating interaction displays different patterns: (i) random
      collaboration, where intralayer or interlayer induction has the same probability;
      (ii) concentrating collaboration, where consecutive intralayer induction is
      guaranteed with a probability of 1; and (iii) cascading collaboration, where
      consecutive intralayer induction is banned with a probability of 0. In this
      paper, we develop a top-bottom framework that uses only two distributions, the
      overlaid degree distribution and edge-type distribution, to model collaborating
      epidemics on multilayer networks. We then state the response of three
      collaborating patterns to structural diversity (evenness and difference of
      network layers). For viral agents with small transmissibility, we find that
      random collaboration is more effective in networks with higher diversity (high
      evenness and difference), while the concentrating pattern is more suitable in
      uneven networks. Interestingly, the cascading pattern requires a network with
      moderate difference and high evenness, and the moderately uneven coupling of
      multiple network layers can effectively increase robustness to resist cascading
      failure. With large transmissibility, however, we find that all collaborating
      patterns are more effective in high-diversity networks. Our work provides a
      systemic analysis of collaborating epidemics on multilayer networks. The results
      enhance our understanding of biotic and informative diffusion through multiple
      vectors. 

PMID- 25615145
TI  - Reconstructing the world trade multiplex: the role of intensive and extensive
      biases.
AB  - In economic and financial networks, the strength of each node has always an
      important economic meaning, such as the size of supply and demand, import and
      export, or financial exposure. Constructing null models of networks matching the
      observed strengths of all nodes is crucial in order to either detect interesting
      deviations of an empirical network from economically meaningful benchmarks or
      reconstruct the most likely structure of an economic network when the latter is
      unknown. However, several studies have proved that real economic networks and
      multiplexes topologically differ from configurations inferred only from node
      strengths. Here we provide a detailed analysis of the world trade multiplex by
      comparing it to an enhanced null model that simultaneously reproduces the
      strength and the degree of each node. We study several temporal snapshots and
      almost 100 layers (commodity classes) of the multiplex and find that the observed
      properties are systematically well reproduced by our model. Our formalism allows
      us to introduce the (static) concept of extensive and intensive bias, defined as
      a measurable tendency of the network to prefer either the formation of extra
      links or the reinforcement of link weights, with respect to a reference case
      where only strengths are enforced. Our findings complement the existing economic
      literature on (dynamic) intensive and extensive trade margins. More generally,
      they show that real-world multiplexes can be strongly shaped by layer-specific
      local constraints. 

PMID- 25615146
TI  - Community detection in networks: Structural communities versus ground truth.
AB  - Algorithms to find communities in networks rely just on structural information
      and search for cohesive subsets of nodes. On the other hand, most scholars
      implicitly or explicitly assume that structural communities represent groups of
      nodes with similar (nontopological) properties or functions. This hypothesis
      could not be verified, so far, because of the lack of network datasets with
      information on the classification of the nodes. We show that traditional
      community detection methods fail to find the metadata groups in many large
      networks. Our results show that there is a marked separation between structural
      communities and metadata groups, in line with recent findings. That means that
      either our current modeling of community structure has to be substantially
      modified, or that metadata groups may not be recoverable from topology alone. 

PMID- 25615147
TI  - Emergence of dynamical complexity related to human heart rate variability.
AB  - We apply the refined composite multiscale entropy (MSE) method to a one
      dimensional directed small-world network composed of nodes whose states are
      binary and whose dynamics obey the majority rule. We find that the resulting
      fluctuating signal becomes dynamically complex. This dynamical complexity is
      caused (i) by the presence of both short-range connections and long-range
      shortcuts and (ii) by how well the system can adapt to the noisy environment. By
      tuning the adaptability of the environment and the long-range shortcuts we can
      increase or decrease the dynamical complexity, thereby modeling trends found in
      the MSE of a healthy human heart rate in different physiological states. When the
      shortcut and adaptability values increase, the complexity in the system dynamics
      becomes uncorrelated. 

PMID- 25615148
TI  - Branching-ratio approximation for the self-exciting Hawkes process.
AB  - We introduce a model-independent approximation for the branching ratio of Hawkes
      self-exciting point processes. Our estimator requires knowing only the mean and
      variance of the event count in a sufficiently large time window, statistics that
      are readily obtained from empirical data. The method we propose greatly
      simplifies the estimation of the Hawkes branching ratio, recently proposed as a
      proxy for market endogeneity and formerly estimated using numerical likelihood
      maximization. We employ our method to support recent theoretical and experimental
      results indicating that the best fitting Hawkes model to describe S&P futures
      price changes is in fact critical (now and in the recent past) in light of the
      long memory of financial market activity. 

PMID- 25615149
TI  - Scaling properties of urban facilities.
AB  - Two measurements are employed to quantitatively investigate the scaling
      properties of the spatial distribution of urban facilities: the K function [whose
      derivative gives the radial distribution function rho(t)=K'(t)/2pit] by number
      counting and the variance-mean relationship by the method of expanding bins. The
      K function and the variance-mean relationship are both power functions. This
      means that the spatial distributions of urban facilities are scaling invariant.
      Further analysis of more data (which includes eight types of facilities in 37
      major Chinese cities) shows that the the power laws broadly hold for all
      combinations of facilities and cities. A double stochastic process (DSP) model is
      proposed as a mathematical mechanism by which spatial point patterns can be
      generated that resemble the actual distribution of urban facilities both
      qualitatively and quantitatively. Simulation of the DSP yields a better agreement
      with the urban data than the correlated percolation model.

PMID- 25615150
TI  - Universal behavior of the interoccurrence times between losses in financial
      markets: independence of the time resolution.
AB  - We consider representative financial records (stocks and indices) on time scales
      between one minute and one day, as well as historical monthly data sets, and show
      that the distribution P(Q)(r) of the interoccurrence times r between losses below
      a negative threshold -Q, for fixed mean interoccurrence times R(Q) in multiples
      of the corresponding time resolutions, can be described on all time scales by the
      same q exponentials, P(Q)(r)?1/{[1+(q-1)betar](1/(q-1))}. We propose that the
      asset- and time-scale-independent analytic form of P(Q)(r) can be regarded as an
      additional stylized fact of the financial markets and represents a nontrivial
      test for market models. We analyze the distribution P(Q)(r) as well as the
      autocorrelation C(Q)(s) of the interoccurrence times for three market models: (i)
      multiplicative random cascades, (ii) multifractal random walks, and (iii) the
      generalized autoregressive conditional heteroskedasticity [GARCH(1,1)] model. We
      find that only one of the considered models, the multifractal random walk model,
      approximately reproduces the q-exponential form of P(Q)(r) and the power-law
      decay of C(Q)(s).

PMID- 25615151
TI  - Analysis of cluster explosive synchronization in complex networks.
AB  - Correlations between intrinsic dynamics and local topology have become a new
      trend in the study of synchronization in complex networks. In this paper, we
      investigate the influence of topology on the dynamics of networks made up of
      second-order Kuramoto oscillators. In particular, based on mean-field
      calculations, we provide a detailed investigation of cluster explosive
      synchronization (CES) [Phys. Rev. Lett. 110, 218701 (2013)] in scale-free
      networks as a function of several topological properties. Moreover, we
      investigate the robustness of discontinuous transitions by including an
      additional quenched disorder, and we show that the phase coherence decreases with
      increasing strength of the quenched disorder. These results complement the
      previous findings regarding CES and also fundamentally deepen the understanding
      of the interplay between topology and dynamics under the constraint of
      correlating natural frequencies and local structure.

PMID- 25615152
TI  - Emergence of energy dependence in the fragmentation of heterogeneous materials.
AB  - The most important characteristics of the fragmentation of heterogeneous solids
      is that the mass (size) distribution of pieces is described by a power law
      functional form. The exponent of the distribution displays a high degree of
      universality depending mainly on the dimensionality and on the brittle-ductile
      mechanical response of the system. Recently, experiments and computer simulations
      have reported an energy dependence of the exponent increasing with the imparted
      energy. These novel findings question the phase transition picture of
      fragmentation phenomena, and have also practical importance for industrial
      applications. Based on large scale computer simulations here we uncover a robust
      mechanism which leads to the emergence of energy dependence in fragmentation
      processes resolving controversial issues on the problem: studying the impact
      induced breakup of platelike objects with varying thickness in three dimensions
      we show that energy dependence occurs when a lower dimensional fragmenting object
      is embedded into a higher dimensional space. The reason is an underlying
      transition between two distinct fragmentation mechanisms controlled by the impact
      velocity at low plate thicknesses, while it is hindered for three-dimensional
      bulk systems. The mass distributions of the subsets of fragments dominated by the
      two cracking mechanisms proved to have an astonishing robustness at all plate
      thicknesses, which implies that the nonuniversality of the complete mass
      distribution is the consequence of blending the contributions of universal
      partial processes. 

PMID- 25615153
TI  - Propagation of economic shocks in input-output networks: a cross-country
      analysis.
AB  - This paper investigates how economic shocks propagate and amplify through the
      input-output network connecting industrial sectors in developed economies. We
      study alternative models of diffusion on networks and we calibrate them using
      input-output data on real-world inter-sectoral dependencies for several European
      countries before the Great Depression. We show that the impact of economic shocks
      strongly depends on the nature of the shock and country size. Shocks that impact
      on final demand without changing production and the technological relationships
      between sectors have on average a large but very homogeneous impact on the
      economy. Conversely, when shocks change also the magnitudes of input-output
      across-sector interdependencies (and possibly sector production), the economy is
      subject to predominantly large but more heterogeneous avalanche sizes. In this
      case, we also find that (i) the more a sector is globally central in the country
      network, the larger its impact; (ii) the largest European countries, such as
      those constituting the core of the European Union's economy, typically experience
      the largest avalanches, signaling their intrinsic higher vulnerability to
      economic shocks. 

PMID- 25615154
TI  - Local quality functions for graph clustering with non-negative matrix
      factorization.
AB  - Many graph clustering quality functions suffer from a resolution limit, namely
      the inability to find small clusters in large graphs. So-called resolution-limit
      free quality functions do not have this limit. This property was previously
      introduced for hard clustering, that is, graph partitioning. We investigate the
      resolution-limit-free property in the context of non-negative matrix
      factorization (NMF) for hard and soft graph clustering. To use NMF in the hard
      clustering setting, a common approach is to assign each node to its highest
      membership cluster. We show that in this case symmetric NMF is not resolution
      limit free, but that it becomes so when hardness constraints are used as part of
      the optimization. The resulting function is strongly linked to the constant Potts
      model. In soft clustering, nodes can belong to more than one cluster, with
      varying degrees of membership. In this setting resolution-limit free turns out to
      be too strong a property. Therefore we introduce locality, which roughly states
      that changing one part of the graph does not affect the clustering of other parts
      of the graph. We argue that this is a desirable property, provide conditions
      under which NMF quality functions are local, and propose a novel class of local
      probabilistic NMF quality functions for soft graph clustering. 

PMID- 25615155
TI  - Influence of autocorrelation on the topology of the climate network.
AB  - Different definitions of links in climate networks may lead to considerably
      different network topologies. We construct a network from climate records of
      surface level atmospheric temperature in different geographical sites around the
      globe using two commonly used definitions of links. Utilizing detrended
      fluctuation analysis, shuffled surrogates, and separation analysis of maritime
      and continental records, we find that one of the major influences on the
      structure of climate networks is due to the autocorrelation in the records, which
      may introduce spurious links. This may explain why different methods could lead
      to different climate network topologies. 

PMID- 25615156
TI  - Threshold cascades with response heterogeneity in multiplex networks.
AB  - Threshold cascade models have been used to describe the spread of behavior in
      social networks and cascades of default in financial networks. In some cases,
      these networks may have multiple kinds of interactions, such as distinct types of
      social ties or distinct types of financial liabilities; furthermore, nodes may
      respond in different ways to influence from their neighbors of multiple types. To
      start to capture such settings in a stylized way, we generalize a threshold
      cascade model to a multiplex network in which nodes follow one of two response
      rules: some nodes activate when, in at least one layer, a large enough fraction
      of neighbors is active, while the other nodes activate when, in all layers, a
      large enough fraction of neighbors is active. Varying the fractions of nodes
      following either rule facilitates or inhibits cascades. Near the inhibition
      regime, global cascades appear discontinuously as the network density increases;
      however, the cascade grows more slowly over time. This behavior suggests a way in
      which various collective phenomena in the real world could appear abruptly yet
      slowly. 

PMID- 25615157
TI  - Correlations between weights and overlap in ensembles of weighted multiplex
      networks.
AB  - Multiplex networks describe a large number of systems ranging from social
      networks to the brain. These multilayer structure encode information in their
      structure. This information can be extracted by measuring the correlations
      present in the multiplex networks structure, such as the overlap of the links in
      different layers. Many multiplex networks are also weighted, and the weights of
      the links can be strongly correlated with the structural properties of the
      multiplex network. For example, in multiplex network formed by the citation and
      collaboration networks between PRE scientists it was found that the statistical
      properties of citations to coauthors differ from the one of citations to
      noncoauthors, i.e., the weights depend on the overlap of the links. Here we
      present a theoretical framework for modeling multiplex weighted networks with
      different types of correlations between weights and overlap. To this end, we use
      the framework of canonical network ensembles, and the recently introduced concept
      of multilinks, showing that null models of a large variety of network structures
      can be constructed in this way. In order to provide a concrete example of how
      this framework apply to real data we consider a multiplex constructed from gene
      expression data of healthy and cancer tissues. 

PMID- 25615158
TI  - Understanding and controlling regime switching in molecular diffusion.
AB  - Diffusion can be strongly affected by ballistic flights (long jumps) as well as
      long-lived sticking trajectories (long sticks). Using statistical inference
      techniques in the spirit of Granger causality, we investigate the appearance of
      long jumps and sticks in molecular-dynamics simulations of diffusion in a
      prototype system, a benzene molecule on a graphite substrate. We find that
      specific fluctuations in certain, but not all, internal degrees of freedom of the
      molecule can be linked to either long jumps or sticks. Furthermore, by changing
      the prevalence of these predictors with an outside influence, the diffusion of
      the molecule can be controlled. The approach presented in this proof of concept
      study is very generic and can be applied to larger and more complex molecules.
      Additionally, the predictor variables can be chosen in a general way so as to be
      accessible in experiments, making the method feasible for control of diffusion in
      applications. Our results also demonstrate that data-mining techniques can be
      used to investigate the phase-space structure of high-dimensional nonlinear
      dynamical systems. 

PMID- 25615159
TI  - Asymptotic dynamics of reflecting spiral waves.
AB  - Resonantly forced spiral waves in excitable media drift in straight-line paths,
      their rotation centers behaving as pointlike objects moving along trajectories
      with a constant velocity. Interaction with medium boundaries alters this velocity
      and may often result in a reflection of the drift trajectory. Such reflections
      have diverse characteristics and are known to be highly nonspecular in general.
      In this context we apply the theory of response functions, which via numerically
      computable integrals, reduces the reaction-diffusion equations governing the
      whole excitable medium to the dynamics of just the rotation center and rotation
      phase of a spiral wave. Spiral reflection trajectories are computed by this
      method for both small- and large-core spiral waves in the Barkley model. Such
      calculations provide insight into the process of reflection as well as
      explanations for differences in trajectories across parameters, including the
      effects of incidence angle and forcing amplitude. Qualitative aspects of these
      results are preserved far beyond the asymptotic limit of weak boundary effects
      and slow resonant drift. 

PMID- 25615160
TI  - Convergent cross-mapping and pairwise asymmetric inference.
AB  - Convergent cross-mapping (CCM) is a technique for computing specific kinds of
      correlations between sets of times series. It was introduced by Sugihara et al.
      [Science 338, 496 (2012).] and is reported to be "a necessary condition for
      causation" capable of distinguishing causality from standard correlation. We show
      that the relationships between CCM correlations proposed by Sugihara et al. do
      not, in general, agree with intuitive concepts of "driving" and as such should
      not be considered indicative of causality. It is shown that the fact that the CCM
      algorithm implies causality is a function of system parameters for simple linear
      and nonlinear systems. For example, in a circuit containing a single resistor and
      inductor, both voltage and current can be identified as the driver depending on
      the frequency of the source voltage. It is shown that the CCM algorithm, however,
      can be modified to identify relationships between pairs of time series that are
      consistent with intuition for the considered example systems for which CCM
      causality analysis provided nonintuitive driver identifications. This
      modification of the CCM algorithm is introduced as "pairwise asymmetric
      inference" (PAI) and examples of its use are presented.

PMID- 25615161
TI  - Localization of low-energy eigenfunctions in Seba billiards.
AB  - We investigate localization of low-energy modes of the Laplacian with a point
      scatterer on a rectangular plate. We observe that the point scatterer acts as a
      barrier confining the low-level modes to one side of the plate while assuming the
      Dirichlet boundary condition at a point does not induce this type of
      localization. This low-energy phenomenon extends to higher modes as we increase
      the eccentricity of the plate. 

PMID- 25615162
TI  - Manipulating matter rogue waves and breathers in Bose-Einstein condensates.
AB  - We construct higher-order rogue wave solutions and breather profiles for the
      quasi-one-dimensional Gross-Pitaevskii equation with a time-dependent interatomic
      interaction and external trap through the similarity transformation technique. We
      consider three different forms of traps: (i) the time-independent expulsive trap,
      (ii) time-dependent monotonous trap, and (iii) time-dependent periodic trap. Our
      results show that when we change a parameter appearing in the time-independent or
      time-dependent trap the second- and third-order rogue waves transform into the
      first-order-like rogue waves. We also analyze the density profiles of breather
      solutions. Here we also show that the shapes of the breathers change when we tune
      the strength of the trap parameter. Our results may help to manage rogue waves
      experimentally in a BEC system. 

PMID- 25615163
TI  - Detecting determinism from point processes.
AB  - The detection of a nonrandom structure from experimental data can be crucial for
      the classification, understanding, and interpretation of the generating process.
      We here introduce a rank-based nonlinear predictability score to detect
      determinism from point process data. Thanks to its modular nature, this approach
      can be adapted to whatever signature in the data one considers indicative of
      deterministic structure. After validating our approach using point process
      signals from deterministic and stochastic model dynamics, we show an application
      to neuronal spike trains recorded in the brain of an epilepsy patient. While we
      illustrate our approach in the context of temporal point processes, it can be
      readily applied to spatial point processes as well. 

PMID- 25615164
TI  - Effect of mixed coupling on relay-coupled Rossler and Lorenz oscillators.
AB  - The complete synchronization between the outermost oscillators using the mixed
      coupling in relay coupled systems is studied. Mixed coupling has two types of
      coupling functions: coupling between similar or dissimilar variables. We examine
      the complete synchronization in relay-coupled systems by the largest transverse
      Lyapunov exponent and synchronization error. We show numerically for Rossler and
      Lorenz oscillators that the combination of these two types of coupling functions
      is able to decrease the critical coupling strength for complete synchronization
      as well as it also suppress oscillations for larger coupling strength. 

PMID- 25615165
TI  - Transitions among the diverse oscillation quenching states induced by the
      interplay of direct and indirect coupling.
AB  - We report the transitions among different oscillation quenching states induced by
      the interplay of diffusive (direct) coupling and environmental (indirect)
      coupling in coupled identical oscillators. This coupling scheme was introduced by
      Resmi et al. [Phys. Rev. E 84, 046212 (2011)] as a general scheme to induce
      amplitude death (AD) in nonlinear oscillators. Using a detailed bifurcation
      analysis we show that, in addition to AD, which actually occurs only in a small
      region of parameter space, this coupling scheme can induce other oscillation
      quenching states, namely oscillation death (OD) and a novel nontrvial AD (NAD)
      state, which is a nonzero bistable homogeneous steady state; more importantly,
      this coupling scheme mediates a transition from the AD state to the OD state and
      a new transition from the AD state to the NAD state. We identify diverse routes
      to the NAD state and map all the transition scenarios in the parameter space for
      periodic oscillators. Finally, we present the first experimental evidence of
      oscillation quenching states and their transitions induced by the interplay of
      direct and indirect coupling.

PMID- 25615166
TI  - Breatherlike solitons extracted from the Peregrine rogue wave.
AB  - Based on the Peregrine solution (PS) of the nonlinear Schrodinger (NLS) equation,
      the evolution of rational fraction pulses surrounded by zero background is
      investigated. These pulses display the behavior of a breatherlike solitons. We
      study the generation and evolution of such solitons extracted, by means of the
      spectral-filtering method, from the PS in the model of the optical fiber with
      realistic values of coefficients accounting for the anomalous dispersion, Kerr
      nonlinearity, and higher-order effects. The results demonstrate that the
      breathing solitons stably propagate in the fibers. Their robustness against small
      random perturbations applied to the initial background is demonstrated too. 

PMID- 25615167
TI  - Finite-N corrections to Vlasov dynamics and the range of pair interactions.
AB  - We explore the conditions on a pair interaction for the validity of the Vlasov
      equation to describe the dynamics of an interacting N-particle system in the
      large N limit. Using a coarse graining in phase space of the exact Klimontovich
      equation for the N-particle system, we evaluate, neglecting correlations of
      density fluctuations, the scalings with N of the terms describing the corrections
      to the Vlasov equation for the coarse-grained one-particle phase space density.
      Considering a generic interaction with radial pair force F(r), with
      F(r)~1/r(gamma) at large scales, and regulated to a bounded behavior below a
      "softening" scale E, we find that there is an essential qualitative difference
      between the cases gamma<d and gamma>d, i.e., depending on the the integrability
      at large distances of the pair force. In the former case, the corrections to the
      Vlasov dynamics for a given coarse-grained scale are essentially insensitive to
      the softening parameter E, while for gamma>d the amplitude of these terms is
      directly regulated by E, and thus by the small scale properties of the
      interaction. This corresponds to a simple physical criterion for a basic
      distinction between long-range (gamma<=d) and short-range (gamma>d) interactions,
      different from the canonical one (gamma<=d+1 or gamma>d+1) based on thermodynamic
      analysis. This alternative classification, based on purely dynamical
      considerations, is relevant notably to understanding the conditions for the
      existence of so-called quasistationary states in long-range interacting systems.

PMID- 25615168
TI  - Shaping wave patterns in reaction-diffusion systems.
AB  - We present a method to control the two-dimensional shape of traveling wave
      solutions to reaction-diffusion systems, such as, interfaces and excitation
      pulses. Control signals that realize a pregiven wave shape are determined
      analytically from nonlinear evolution equation for isoconcentration lines as the
      perturbed nonlinear phase diffusion equation or the perturbed linear eikonal
      equation. While the control enforces a desired wave shape perpendicular to the
      local propagation direction, the wave profile along the propagation direction
      itself remains almost unaffected. Provided that the one-dimensional wave profile
      of all state variables and its propagation velocity can be measured
      experimentally, and the diffusion coefficients of the reacting species are given,
      the new approach can be applied even if the underlying nonlinear reaction
      kinetics are unknown. 

PMID- 25615169
TI  - Classification of wave regimes in excitable systems with linear cross diffusion.
AB  - We consider principal properties of various wave regimes in two selected
      excitable systems with linear cross diffusion in one spatial dimension observed
      at different parameter values. This includes fixed-shape propagating waves,
      envelope waves, multienvelope waves, and intermediate regimes appearing as waves
      propagating at a fixed shape most of the time but undergoing restructuring from
      time to time. Depending on parameters, most of these regimes can be with and
      without the "quasisoliton" property of reflection of boundaries and penetration
      through each other. We also present some examples of the behavior of envelope
      quasisolitons in two spatial dimensions. 

PMID- 25615170
TI  - Mechanism for intensity-induced chimera states in globally coupled oscillators.
AB  - We identify the mechanism behind the existence of intensity-induced chimera
      states in globally coupled oscillators. We find that the effect of intensity in
      the system is to cause multistability by increasing the number of fixed points.
      This in turn increases the number of multistable attractors, and we find that
      their stability is determined by the strength of coupling. This causes the
      coexistence of different collective states in the system depending upon the
      initial state. We demonstrate that intensity-induced chimera is generic to both
      periodic and chaotic systems. We discuss possible applications of our results to
      real-world systems like the brain and spin torque nano-oscillators. 

PMID- 25615171
TI  - Thermodynamic characterization of synchronization-optimized oscillator networks.
AB  - We consider a canonical ensemble of synchronization-optimized networks of
      identical oscillators under external noise. By performing a Markov chain Monte
      Carlo simulation using the Kirchhoff index, i.e., the sum of the inverse
      eigenvalues of the Laplacian matrix (as a graph Hamiltonian of the network), we
      construct more than 1,000 different synchronization-optimized networks. We then
      show that the transition from star to core-periphery structure depends on the
      connectivity of the network, and is characterized by the node degree variance of
      the synchronization-optimized ensemble. We find that thermodynamic properties
      such as heat capacity show anomalies for sparse networks.

PMID- 25615172
TI  - Turing pattern dynamics in an activator-inhibitor system with superdiffusion.
AB  - The fractional operator is introduced to an activator-inhibitor system to
      describe species anomalous superdiffusion. The effects of the superdiffusive
      exponent on pattern formation and pattern selection are studied. Our linear
      stability analysis shows that the wave number of the Turing pattern increases
      with the superdiffusive exponent. A weakly nonlinear analysis yields a system of
      amplitude equations and the analysis of these amplitude equations predicts
      parameter regimes where hexagons, stripes, and their coexistence are expected.
      Numerical simulations of the activator-inhibitor model near the stability
      boundaries confirm our analytical results. Since diffusion rate manifests in both
      diffusion constant and diffusion exponent, we numerically explore their
      interactions on the emergence of Turing patterns. When the activator and
      inhibitor have different superdiffusive exponents, we find that the critical
      ratio of the diffusion rate of the inhibitor to the activator, required for the
      formation of the Turing pattern, increases monotonically with the superdiffusive
      exponent. We conclude that small ratio (than unity) of anomalous diffusion
      exponent between the inhibitor and activator is more likely to promote the
      emergence of the Turing pattern, relative to the normal diffusion. 

PMID- 25615173
TI  - Using waveform information in nonlinear data assimilation.
AB  - Information in measurements of a nonlinear dynamical system can be transferred to
      a quantitative model of the observed system to establish its fixed parameters and
      unobserved state variables. After this learning period is complete, one may
      predict the model response to new forces and, when successful, these predictions
      will match additional observations. This adjustment process encounters problems
      when the model is nonlinear and chaotic because dynamical instability impedes the
      transfer of information from the data to the model when the number of
      measurements at each observation time is insufficient. We discuss the use of
      information in the waveform of the data, realized through a time delayed
      collection of measurements, to provide additional stability and accuracy to this
      search procedure. Several examples are explored, including a few familiar
      nonlinear dynamical systems and small networks of Colpitts oscillators. 

PMID- 25615174
TI  - Triple grouping and period-three oscillations in minority-game dynamics.
AB  - Dynamical systems based on the minority game (MG) have been a paradigm for
      gaining significant insights into a variety of social and biological behaviors.
      Recently, a grouping phenomenon has been unveiled in MG systems of multiple
      resources (strategies) in which the strategies spontaneously break into an even
      number of groups, each exhibiting an identical oscillation pattern in the
      attendance of game players. Here we report our finding of spontaneous breakup of
      resources into three groups, each exhibiting period-three oscillations. An
      analysis is developed to understand the emergence of the striking phenomenon of
      triple grouping and period-three oscillations. In the presence of random
      disturbances, the triple-group/period-three state becomes transient, and we
      obtain explicit formula for the average transient lifetime using two methods of
      approximation. Our finding indicates that, period-three oscillation, regarded as
      one of the most fundamental behaviors in smooth nonlinear dynamical systems, can
      also occur in much more complex, evolutionary-game dynamical systems. Our result
      also provides a plausible insight for the occurrence of triple grouping observed,
      for example, in the U.S. housing market. 

PMID- 25615175
TI  - Chaotic dynamics of one-dimensional systems with periodic boundary conditions.
AB  - We provide appropriate tools for the analysis of dynamics and chaos for one
      dimensional systems with periodic boundary conditions. Our approach allows for
      the investigation of the dependence of the largest Lyapunov exponent on various
      initial conditions of the system. The method employs an effective approach for
      defining the phase-space distance appropriate for systems with periodic
      boundaries and allows for an unambiguous test-orbit rescaling in the phase space
      required to calculate the Lyapunov exponents. We elucidate our technique by
      applying it to investigate the chaotic dynamics of a one-dimensional plasma with
      periodic boundaries. Exact analytic expressions are derived for the electric
      field and potential using Ewald sums, thereby making it possible to follow the
      time evolution of the plasma in simulations without any special treatment of the
      boundary. By employing a set of event-driven algorithms, we calculate the largest
      Lyapunov exponent, the radial distribution function, and the pressure by
      following the evolution of the system in phase space without resorting to
      numerical manipulation of the equations of motion. Simulation results are
      presented and analyzed for the one-dimensional plasma with a view to examining
      the dynamical and chaotic behavior exhibited by small and large versions of the
      system. 

PMID- 25615176
TI  - Nonlinear dynamics of atoms in a crossed optical dipole trap.
AB  - We explore the classical dynamics of atoms in an optical dipole trap formed by
      two identical Gaussian beams propagating in perpendicular directions. The phase
      space is a mixture of regular and chaotic orbits, the latter becoming dominant as
      the energy of the atoms increases. The trapping capabilities of these
      perpendicular Gaussian beams are investigated by considering an atomic ensemble
      in free motion. After a sudden turn on of the dipole trap, a certain fraction of
      atoms in the ensemble remains trapped. The majority of these trapped atoms has
      energies larger than the escape channels, which can be explained by the existence
      of regular and chaotic orbits with very long escape times. 

PMID- 25615177
TI  - Statistical properties of the maximum Lyapunov exponent calculated via the
      divergence rate method.
AB  - The embedding of a time series provides a basic tool to analyze dynamical
      properties of the underlying chaotic system. To this purpose, the choice of the
      embedding dimension and lag is crucial. Although several methods have been
      devised to tackle the issue of the optimal setting of these parameters, a
      conclusive criterion to make the most appropriate choice is still lacking. An
      accepted procedure to rank different embedding methods relies on the evaluation
      of the maximum Lyapunov exponent (MLE) out of embedded time series that are
      generated by chaotic systems with explicit analytic representation. The MLE is
      evaluated as the local divergence rate of nearby trajectories. Given a system,
      embedding methods are ranked according to how close such MLE values are to the
      true MLE. This is provided by the so-called standard method in a way that
      exploits the mathematical description of the system and does not require
      embedding. In this paper we study the dependence of the finite-time MLE evaluated
      via the divergence rate method on the embedding dimension and lag in the case of
      time series generated by four systems that are widely used as references in the
      scientific literature. We develop a completely automatic algorithm that provides
      the divergence rate and its statistical uncertainty. We show that the uncertainty
      can provide useful information about the optimal choice of the embedding
      parameters. In addition, our approach allows us to find which systems provide
      suitable benchmarks for the comparison and ranking of different embedding
      methods. 

PMID- 25615178
TI  - Quantification of causal couplings via dynamical effects: a unifying perspective.
AB  - Quantitative characterization of causal couplings from time series is crucial in
      studies of complex systems of different origin. Various statistical tools for
      that exist and new ones are still being developed with a tendency to creating a
      single, universal, model-free quantifier of coupling strength. However, a clear
      and generally applicable way of interpreting such universal characteristics is
      lacking. This work suggests a general conceptual framework for causal coupling
      quantification, which is based on state space models and extends the concepts of
      virtual interventions and dynamical causal effects. Namely, two basic kinds of
      interventions (state space and parametric) and effects (orbital or transient and
      stationary or limit) are introduced, giving four families of coupling
      characteristics. The framework provides a unifying view of apparently different
      well-established measures and allows us to introduce new characteristics, always
      with a definite "intervention-effect" interpretation. It is shown that diverse
      characteristics cannot be reduced to any single coupling strength quantifier and
      their interpretation is inevitably model based. The proposed set of dynamical
      causal effect measures quantifies different aspects of "how the coupling
      manifests itself in the dynamics," reformulating the very question about the
      "causal coupling strength." 

PMID- 25615179
TI  - Discrete and continuum composite solitons in Bose-Einstein condensates with the
      Rashba spin-orbit coupling in one and two dimensions.
AB  - We introduce one- and two-dimensional (1D and 2D) continuum and discrete models
      for the two-component BEC, with the spin-orbit (SO) coupling of the Rashba type
      between the components, and attractive cubic interactions, assuming that the
      condensate is fragmented into a quasidiscrete state by a deep optical-lattice
      potential. In 1D, it is demonstrated, in analytical and numerical forms, that the
      ground states of both the discrete system and its continuum counterpart switch
      from striped bright solitons, featuring deep short-wave modulations of its
      profile, to smooth solitons, as the strength ratio of the inter- and
      intracomponent attraction, gamma, changes from gamma<1 to gamma>1. At the
      borderline, gamma=1, there is a continuous branch of stable solitons, which share
      a common value of the energy and interpolate between the striped and smooth ones.
      Unlike the 2D system, the 1D solitons, which do not represent the ground state at
      given gamma, are nevertheless stable against small perturbations, and they remain
      stable too in collisions with other solitons. In 2D, a transition between two
      different types of discrete solitons, which represent the ground state, viz.,
      semivortices and mixed modes, also takes place at gamma=1. A specific property of
      2D discrete solitons of both types is their discontinuous transition into a
      delocalized state at a critical value of the SO-coupling strength. We also
      address the continuum 2D model in the borderline case of gamma=1, which was not
      studied previously, and demonstrate the existence of an energy-degenerate branch
      of dynamically stable solitons connecting the semivortex and the mixed mode.
      Last, it is demonstrated that 1D and 2D discrete solitons are mobile, in a
      limited interval of velocities. 

PMID- 25615180
TI  - Statistics of the island-around-island hierarchy in Hamiltonian phase space.
AB  - The phase space of a typical Hamiltonian system contains both chaotic and regular
      orbits, mixed in a complex, fractal pattern. One oft-studied phenomenon is the
      algebraic decay of correlations and recurrence time distributions. For area
      preserving maps, this has been attributed to the stickiness of boundary circles,
      which separate chaotic and regular components. Though such dynamics has been
      extensively studied, a full understanding depends on many fine details that
      typically are beyond experimental and numerical resolution. This calls for a
      statistical approach, the subject of the present work. We calculate the
      statistics of the boundary circle winding numbers, contrasting the distribution
      of the elements of their continued fractions to that for uniformly selected
      irrationals. Since phase space transport is of great interest for dynamics, we
      compute the distributions of fluxes through island chains. Analytical fits show
      that the "level" and "class" distributions are distinct, and evidence for their
      universality is given. 

PMID- 25615181
TI  - Evolution of length scales and statistics of Richtmyer-Meshkov instability from
      direct numerical simulations.
AB  - In this study we present direct numerical simulation results of the Richtmyer
      Meshkov instability (RMI) initiated by Ma=1.05,Ma=1.2, and Ma=1.5 shock waves
      interacting with a perturbed planar interface between air and SF(6). At the
      lowest shock Mach number the fluids slowly mix due to viscous diffusion, whereas
      at the highest shock Mach number the mixing zone becomes turbulent. When a
      minimum critical Taylor microscale Reynolds number is exceeded, an inertial range
      spectrum emerges, providing further evidence of transition to turbulence. The
      scales of turbulent motion, i.e., the Kolmogorov length scale, the Taylor
      microscale, and the integral length, scale are presented. The separation of these
      scales is found to increase as the Reynolds number is increased. Turbulence
      statistics, i.e., the probability density functions of the velocity and its
      longitudinal and transverse derivatives, show a self-similar decay and thus that
      turbulence evolving from RMI is not fundamentally different from isotropic
      turbulence, though nominally being only isotropic and homogeneous in the
      transverse directions.

PMID- 25615182
TI  - Comparative numerical-experimental analysis of the universal impact of arbitrary
      perturbations on transport in three-dimensional unsteady flows.
AB  - Numerical studies of three-dimensional (3D) time-periodic flow inside a lid
      driven cylinder revealed that a weak perturbation of the noninertial state
      (Reynolds number Re=0) has a strong impact on the Lagrangian flow structure by
      inducing transition of a global family of nested spheroidal invariant surfaces
      into intricate coherent structures consisting of adiabatic invariant surfaces
      connected by tubes. These tubes provide paths for passive tracers to escape from
      one invariant surface to another. Perturbation is introduced in two ways: (i)
      weak fluid inertia by nonzero Re~O(10(-3)); (ii) small disturbance of the
      external flow forcing. Both induce essentially the same dynamics, implying a
      universal response in the limit of a weak perturbation. Moreover, we show that
      the motion inside tubes possesses an adiabatic invariant. Long-term experiments
      were conducted using 3D particle-tracking velocimetry and relied on experimental
      imperfections as natural weak perturbations. This provided first experimental
      evidence of the tube formation and revealed close agreement with numerical
      simulations. We experimentally validated the universality of the perturbation
      response and, given the inevitability of imperfections, exposed the weakly
      perturbed state as the true "unperturbed state" in realistic systems.

PMID- 25615183
TI  - Influence of container shape on scaling of turbulent fluctuations in convection.
AB  - We perform large-eddy simulations of turbulent convection in a cubic cell for
      Rayleigh numbers, Ra, between 10(6) and 10(10) and the molecular Prandtl number,
      Pr=0.7. The simulations were carried out using a second-order-accurate finite
      difference method in which subgrid-scale fluxes of momentum and heat were both
      parametrized using a Lagrangian and dynamic Smagorinsky model. The scaling of the
      root-mean-square fluctuations of density (temperature) and velocity measured in
      the cell center are in excellent agreement with the scaling measured in the
      laboratory experiments of Daya and Ecke [Phys. Rev. Lett. 87, 184501 (2001)] and
      differ substantially from that observed in cylindrical cells. We also observe the
      time-averaged spatial distributions of the local heat flux and density
      fluctuations, and find that they are strongly inhomogeneous in the horizontal
      midplane, with the largest density gradients occurring at the corners at the
      midheight, where hot and cold plumes mix in the form of strong counter-rotating
      eddies.

PMID- 25615184
TI  - Single-wave-number representation of nonlinear energy spectrum in elastic-wave
      turbulence of the Foppl-von Karman equation: energy decomposition analysis and
      energy budget.
AB  - A single-wave-number representation of a nonlinear energy spectrum, i.e., a
      stretching-energy spectrum, is found in elastic-wave turbulence governed by the
      Foppl-von Karman (FvK) equation. The representation enables energy decomposition
      analysis in the wave-number space and analytical expressions of detailed energy
      budgets in the nonlinear interactions. We numerically solved the FvK equation and
      observed the following facts. Kinetic energy and bending energy are comparable
      with each other at large wave numbers as the weak turbulence theory suggests. On
      the other hand, stretching energy is larger than the bending energy at small wave
      numbers, i.e., the nonlinearity is relatively strong. The strong correlation
      between a mode a(k) and its companion mode a(-k) is observed at the small wave
      numbers. The energy is input into the wave field through stretching-energy
      transfer at the small wave numbers, and dissipated through the quartic part of
      kinetic-energy transfer at the large wave numbers. Total-energy flux consistent
      with energy conservation is calculated directly by using the analytical
      expression of the total-energy transfer, and the forward energy cascade is
      observed clearly.

PMID- 25615185
TI  - Phenomenology of nonrelativistic parity-violating hydrodynamics in 2+1
      dimensions.
AB  - Parity-violating fluids in two spatial dimensions can appear in a variety of
      contexts such as liquid crystal films, anyon fluids, and quantum Hall fluids.
      Nonetheless, the consequences of parity violation on the solutions to the
      equations of motion are largely unexplored. In this paper, we explore
      phenomenological consequences of parity violation through simple, illustrative
      examples. Although incompressible velocity fields are essentially unchanged by
      parity violation, we discuss examples where parity violation plays a role at
      boundaries, or in the dynamics of temperature. We then discuss types of
      compressible flows which only exist in a parity-violating fluid, including sound
      waves, and solitons in the dissipationless limit. We conclude with a discussion
      of some curious features in Rayleigh-Benard convection of a parity-violating
      fluid. 

PMID- 25615186
TI  - Modeling rigid magnetically rotated microswimmers: rotation axes, bistability,
      and controllability.
AB  - Magnetically actuated microswimmers have recently attracted attention due to many
      possible biomedical applications. In this study we investigate the dynamics of
      rigid magnetically rotated microswimmers with permanent magnetic dipoles. Our
      approach uses a boundary element method to calculate a mobility matrix, accurate
      for arbitrary geometries, which is then used to identify the steady periodically
      rotating orbits in a co-rotating body-fixed frame. We evaluate the stability of
      each of these orbits. We map the magnetoviscous behavior as a function of
      dimensionless Mason number and as a function of the angle that the magnetic field
      makes with its rotation axis. We describe the wobbling motion of these swimmers
      by investigating how the rotation axis changes as a function of experimental
      parameters. We show that for a given magnetic field strength and rotation
      frequency, swimmers can have more than one stable periodic orbit with different
      rotation axes. Finally, we demonstrate that one can improve the controllability
      of these types of microswimmers by adjusting the relative angle between the
      magnetic field and its axis of rotation. 

PMID- 25615187
TI  - Acoustic interaction forces between small particles in an ideal fluid.
AB  - We present a theoretical expression for the acoustic interaction force between
      small spherical particles suspended in an ideal fluid exposed to an external
      acoustic wave. The acoustic interaction force is the part of the acoustic
      radiation force on one given particle involving the scattered waves from the
      other particles. The particles, either compressible liquid droplets or elastic
      microspheres, are considered to be much smaller than the acoustic wavelength. In
      this so-called Rayleigh limit, the acoustic interaction forces between the
      particles are well approximated by gradients of pair-interaction potentials with
      no restriction on the interparticle distance. The theory is applied to studies of
      the acoustic interaction force on a particle suspension in either standing or
      traveling plane waves. The results show aggregation regions along the wave
      propagation direction, while particles may attract or repel each other in the
      transverse direction. In addition, a mean-field approximation is developed to
      describe the acoustic interaction force in an emulsion of oil droplets in water. 

PMID- 25615188
TI  - Cospectral budget of turbulence explains the bulk properties of smooth pipe flow.
AB  - Connections between the wall-normal turbulent velocity spectrum E(ww)(k) at wave
      number k and the mean velocity profile (MVP) are explored in pressure-driven
      flows confined within smooth walls at moderate to high bulk Reynolds numbers
      (Re). These connections are derived via a cospectral budget for the longitudinal
      (u') and wall-normal (w') velocity fluctuations, which include a production term
      due to mean shear interacting with E(ww)(k), viscous effects, and a decorrelation
      between u' and w' by pressure-strain effects [=pi(k)]. The pi(k) is modeled using
      a conventional Rotta-like return-to-isotropy closure but adjusted to include the
      effects of isotropization of the production term. The resulting cospectral budget
      yields a generalization of a previously proposed "spectral link" between the MVP
      and the spectrum of turbulence. The proposed cospectral budget is also shown to
      reproduce the measured MVP across the pipe with changing Re including the MVP
      shapes in the buffer and wake regions. Because of the links between E(ww)(k) and
      the MVP, the effects of intermittency corrections to inertial subrange scales and
      the so-called spectral bottleneck reported as k approaches viscous dissipation
      eddy sizes (eta) on the MVP shapes are investigated and shown to be of minor
      importance. Inclusion of a local Reynolds number correction to a parameter
      associated with the spectral exponential cutoff as keta->1 appears to be more
      significant to the MVP shape in the buffer region. While the bulk shape of the
      MVP is reasonably reproduced in all regions of the pipe, the solution to the
      cospectral budget systematically underestimates the negative curvature of the MVP
      within the buffer layer.

PMID- 25615189
TI  - Stationary patterns in centrifugally driven interfacial elastic fingering.
AB  - A vortex sheet formalism is used to search for equilibrium shapes in the
      centrifugally driven interfacial elastic fingering problem. We study the
      development of interfacial instabilities when a viscous fluid surrounded by
      another of smaller density flows in the confined environment of a rotating Hele
      Shaw cell. The peculiarity of the situation is associated to the fact that, due
      to a chemical reaction, the two-fluid boundary becomes an elastic layer. The
      interplay between centrifugal and elastic forces leads to the formation of a rich
      variety of stationary shapes. Visually striking equilibrium morphologies are
      obtained from the numerical solution of a nonlinear differential equation for the
      interface curvature (the shape equation), determined by a zero vorticity
      condition. Classification of the various families of shapes is made via two
      dimensionless parameters: an effective bending rigidity (ratio of elastic to
      centrifugal effects) and a geometrical radius of gyration. 

PMID- 25615190
TI  - Effect of direct bubble-bubble interactions on linear-wave propagation in bubbly
      liquids.
AB  - We study the influence of bubble-bubble interactions on the propagation of linear
      acoustic waves in bubbly liquids. Using the full model proposed by Fuster and
      Colonius [J. Fluid Mech. 688, 253 (2011)], numerical simulations reveal that
      direct bubble-bubble interactions have an appreciable effect for frequencies
      above the natural resonance frequency of the average size bubble. Based on the
      new results, a modification of the classical wave propagation theory is proposed.
      The results obtained are in good agreement with previously reported experimental
      data where the classical linear theory systematically overpredicts the effective
      attenuation and phase velocity.

PMID- 25615191
TI  - Smoothed particle hydrodynamics and element bending group modeling of flexible
      fibers interacting with viscous fluids.
AB  - This paper presents a smoothed particle hydrodynamics (SPH) and element bending
      group (EBG) coupling method for modeling the interaction of flexible fibers with
      moving viscous fluids. SPH is a well-developed mesh-free particle method for
      simulating viscous fluid flows. EBG is also a particle method for modeling
      flexible bodies. The interaction of flexible fibers with moving viscous fluids is
      rendered through the interaction of EBG particles for flexible fiber and SPH
      particles for fluid. In numerical simulation, flexible fibers of different
      lengths are immersed in a moving viscous fluid driven by a body force. The drag
      force on the fiber obtained from SPH-EBG simulation agrees well with experimental
      observations. It is shown that the flexible fiber demonstrates three typical
      bending modes, including the U-shaped mode, the flapping mode, and the closed
      mode, and that the flexible fiber experiences a drag reduction due to its
      reconfiguration by bending. It is also found that the U4/3 drag scaling law for a
      flexible fiber is only valid for the U-shaped mode, but not valid for the
      flapping and closed modes. The results indicate that the reconfiguration of a
      flexible fiber is caused by the fluid force acting on it, while vortex shedding
      is of importance in the translations of bending modes. 

PMID- 25615192
TI  - Anomalous transport and chaotic advection in homogeneous porous media.
AB  - The topological complexity inherent to all porous media imparts persistent
      chaotic advection under steady flow conditions, which, in concert with the no
      slip boundary condition, generates anomalous transport. We explore the impact of
      this mechanism upon longitudinal dispersion via a model random porous network and
      develop a continuous-time random walk that predicts both preasymptotic and
      asymptotic transport. In the absence of diffusion, the ergodicity of chaotic
      fluid orbits acts to suppress longitudinal dispersion from ballistic to
      superdiffusive transport, with asymptotic variance scaling as
      sigma(L)(2)(t)~t(2)/(ln t)(3). These results demonstrate that anomalous transport
      is inherent to homogeneous porous media and has significant implications for
      macrodispersion.

PMID- 25615193
TI  - Spectral calculations in stably stratified turbulence.
AB  - We perform a Leslie-type perturbative treatment on stably stratified turbulence
      with Boussinesq approximation, where the buoyancy terms in the corresponding
      dynamical equations are treated as perturbations against the isotropic background
      fields. Thus we calculate the anisotropic corrections to various correlation
      functions, namely, velocity-velocity, temperature-temperature, and velocity
      temperature correlations, up to second order in this scheme. We find that the
      prefactors associated with the anisotropic corrections depend on the energy flux,
      scalar flux, Kolmogorov constant, Batchelor constant, and the eddy-damping
      amplitudes. The correlation functions further yield the anisotropic parts of the
      energy and mean-square temperature spectra as k(-3) and the anisotropic buoyancy
      spectrum as k(-7/3). The resulting angle-dependent energy density is found to be
      concentrated predominantly around the vertical wave vector signifying layered
      structures in the physical space.

PMID- 25615194
TI  - Cross-correlation-aided transport in stochastically driven accretion flows.
AB  - The origin of linear instability resulting in rotating sheared accretion flows
      has remained a controversial subject for a long time. While some explanations of
      such non-normal transient growth of disturbances in the Rayleigh stable limit
      were available for magnetized accretion flows, similar instabilities in the
      absence of magnetic perturbations remained unexplained. This dichotomy was
      resolved in two recent publications by Chattopadhyay and co-workers [Mukhopadhyay
      and Chattopadhyay, J. Phys. A 46, 035501 (2013); Nath et al., Phys. Rev. E 88,
      013010 (2013)] where it was shown that such instabilities, especially for
      nonmagnetized accretion flows, were introduced through interaction of the
      inherent stochastic noise in the system (even a "cold" accretion flow at 3000 K
      is too "hot" in the statistical parlance and is capable of inducing strong
      thermal modes) with the underlying Taylor-Couette flow profiles. Both studies,
      however, excluded the additional energy influx (or efflux) that could result from
      nonzero cross correlation of a noise perturbing the velocity flow, say, with the
      noise that is driving the vorticity flow (or equivalently the magnetic field and
      magnetic vorticity flow dynamics). Through the introduction of such a time
      symmetry violating effect, in this article we show that nonzero noise cross
      correlations essentially renormalize the strength of temporal correlations. Apart
      from an overall boost in the energy rate (both for spatial and temporal
      correlations, and hence in the ensemble averaged energy spectra), this results in
      mutual competition in growth rates of affected variables often resulting in
      suppression of oscillating Alfven waves at small times while leading to faster
      saturations at relatively longer time scales. The effects are seen to be more
      pronounced with magnetic field fluxes where the noise cross correlation magnifies
      the strength of the field concerned. Another remarkable feature noted
      specifically for the autocorrelation functions is the removal of energy
      degeneracy in the temporal profiles of fast growing non-normal modes leading to
      faster saturation with minimum oscillations. These results, including those
      presented in the previous two publications, now convincingly explain subcritical
      transition to turbulence in the linear limit for all possible situations that
      could now serve as the benchmark for nonlinear stability studies in Keplerian
      accretion disks.

PMID- 25615195
TI  - Self-similarity in the inertial region of wall turbulence.
AB  - The inverse of the von Karman constant kappa is the leading coefficient in the
      equation describing the logarithmic mean velocity profile in wall bounded
      turbulent flows. Klewicki [J. Fluid Mech. 718, 596 (2013)] connects the
      asymptotic value of kappa with an emerging condition of dynamic self-similarity
      on an interior inertial domain that contains a geometrically self-similar
      hierarchy of scaling layers. A number of properties associated with the
      asymptotic value of kappa are revealed. This is accomplished using a framework
      that retains connection to invariance properties admitted by the mean statement
      of dynamics. The development leads toward, but terminates short of, analytically
      determining a value for kappa. It is shown that if adjacent layers on the
      hierarchy (or their adjacent positions) adhere to the same self-similarity that
      is analytically shown to exist between any given layer and its position, then
      kappa=Phi(-2)=0.381966..., where Phi=(1+?5)/2 is the golden ratio. A number of
      measures, derived specifically from an analysis of the mean momentum equation,
      are subsequently used to empirically explore the veracity and implications of
      kappa=Phi(-2). Consistent with the differential transformations underlying an
      invariant form admitted by the governing mean equation, it is demonstrated that
      the value of kappa arises from two geometric features associated with the
      inertial turbulent motions responsible for momentum transport. One nominally
      pertains to the shape of the relevant motions as quantified by their area
      coverage in any given wall-parallel plane, and the other pertains to the changing
      size of these motions in the wall-normal direction. In accord with self-similar
      mean dynamics, these two features remain invariant across the inertial domain.
      Data from direct numerical simulations and higher Reynolds number experiments are
      presented and discussed relative to the self-similar geometric structure
      indicated by the analysis, and in particular the special form of self-similarity
      shown to correspond to kappa=Phi(-2).

PMID- 25615196
TI  - Anomalous scaling of passive scalar fields advected by the Navier-Stokes velocity
      ensemble: effects of strong compressibility and large-scale anisotropy.
AB  - The field theoretic renormalization group and the operator product expansion are
      applied to two models of passive scalar quantities (the density and the tracer
      fields) advected by a random turbulent velocity field. The latter is governed by
      the Navier-Stokes equation for compressible fluid, subject to external random
      force with the covariance ?delta(t-t')k(4-d-y), where d is the dimension of space
      and y is an arbitrary exponent. The original stochastic problems are reformulated
      as multiplicatively renormalizable field theoretic models; the corresponding
      renormalization group equations possess infrared attractive fixed points. It is
      shown that various correlation functions of the scalar field, its powers and
      gradients, demonstrate anomalous scaling behavior in the inertial-convective
      range already for small values of y. The corresponding anomalous exponents,
      identified with scaling (critical) dimensions of certain composite fields
      ("operators" in the quantum-field terminology), can be systematically calculated
      as series in y. The practical calculation is performed in the leading one-loop
      approximation, including exponents in anisotropic contributions. It should be
      emphasized that, in contrast to Gaussian ensembles with finite correlation time,
      the model and the perturbation theory presented here are manifestly Galilean
      covariant. The validity of the one-loop approximation and comparison with
      Gaussian models are briefly discussed.

PMID- 25615197
TI  - Interaction of two walkers: wave-mediated energy and force.
AB  - A bouncing droplet, self-propelled by its interaction with the waves it
      generates, forms a classical wave-particle association called a "walker."
      Previous works have demonstrated that the dynamics of a single walker is driven
      by its global surface wave field that retains information on its past trajectory.
      Here we investigate the energy stored in this wave field for two coupled walkers
      and how it conveys an interaction between them. For this purpose, we characterize
      experimentally the "promenade modes" where two walkers are bound and propagate
      together. Their possible binding distances take discrete values, and the velocity
      of the pair depends on their mutual binding. The mean parallel motion can be
      either rectilinear or oscillating. The experimental results are recovered
      analytically with a simple theoretical framework. A relation between the kinetic
      energy of the droplets and the total energy of the standing waves is established.

PMID- 25615198
TI  - Probing the energy cascade of convective turbulence.
AB  - The existence of a buoyancy-dominated scaling range in convective turbulence is a
      longstanding open question. We investigate this issue by considering the scale-by
      scale energy budget in direct numerical simulations of Rayleigh-Benard
      convection. We try to minimize the so-called Bolgiano length scale, the length
      scale at which buoyancy becomes dominant for scaling. Therefore, we deliberately
      choose modest Rayleigh numbers Ra=2.5*10(6) and 2.5*10(7). The budget reveals
      that buoyant forcing, turbulent energy transfer, and dissipation are contributing
      significantly over a wide range of scales. Thereby neither Kolmogorov-like
      (balance of turbulent transfer and dissipation) nor Bolgiano-Obukhov-like scaling
      (balance of turbulent transfer and buoyancy) is expected in the structure
      functions, which indeed reveal inconclusive scaling behavior. Furthermore, we
      consider the calculation of the Bolgiano length scale. To account for
      correlations between the dissipation rates of kinetic energy and thermal variance
      we propose to average the Bolgiano length scale directly. This gives an estimate,
      which is one order of magnitude larger than the previous estimate, and actually
      larger than the domain itself. Rather than studying the scaling of structure
      functions, we propose that the use of scale-by-scale energy budgets resolving
      anisotropic contributions is appropriate to consider the energy cascade
      mechanisms in turbulent convection.

PMID- 25615199
TI  - Self-focusing and jet instability of a microswimmer suspension.
AB  - Three-dimensional (3D) numerical simulations are performed on suspensions
      composed of puller-like microswimmers that are sensitive to light (phototaxis)
      mimicking microalgae in a Poiseuille flow. Simulations are based on the numerical
      resolution of the flow equations at low Reynolds numbers discretized on a 3D grid
      (finite differences). The model reproduces the formation of a central jet of
      swimmers by self-focusing [Phys. Rev. Lett. 110, 138106 (2013)] but also predicts
      an instability of the jet, which leads to its fractionation in clusters. We show
      that this instability is due to hydrodynamic interactions between microswimmers,
      which attract each other along the flow direction. This effect was not observed
      in the experiments conducted on dilute suspensions (i.e., where hydrodynamic
      interactions are weak). This phenomenon is peculiar for pullers for which
      collective motions are usually not observed on such a time scale. With this
      modeling, we hope to pave the way toward a better understanding of concentration
      techniques of algae (a bottleneck challenge in industrial applications).

PMID- 25615200
TI  - Compact hohlraum configuration with parallel planar-wire-array x-ray sources at
      the 1.7-MA Zebra generator.
AB  - A compact Z-pinch x-ray hohlraum design with parallel-driven x-ray sources is
      experimentally demonstrated in a configuration with a central target and tailored
      shine shields at a 1.7-MA Zebra generator. Driving in parallel two magnetically
      decoupled compact double-planar-wire Z pinches has demonstrated the generation of
      synchronized x-ray bursts that correlated well in time with x-ray emission from a
      central reemission target. Good agreement between simulated and measured hohlraum
      radiation temperature of the central target is shown. The advantages of compact
      hohlraum design applications for multi-MA facilities are discussed. 

PMID- 25615201
TI  - Charge on luminous bodies resembling natural ball lightning produced via
      electrical arcs through lump silicon.
AB  - A phenomenon resembling natural ball lightning can be produced via electrical
      arcing through silicon. We use lump silicon instead of silicon wafers to achieve
      higher production rates and larger, longer-lived luminous balls than previously
      reported. The luminous balls consist of a silicon core surrounded by a porous
      network of loosely bound silicon dioxide nanoparticles. We find that the balls
      carry a small net charge on the order of 10(-12) C and propose that the
      nanoparticles are electrostatically bound to the core due to this charge.

PMID- 25615202
TI  - Experimental confirmation of self-regulating turbulence paradigm in two
      dimensional spectral condensation.
AB  - Turbulent transport in magnetic fusion plasmas can be significantly suppressed by
      Reynolds-stress-induced zonal flows, allowing effective plasma confinement. We
      present experimental evidence of spatiotemporal correlation between small-scale
      turbulence-induced Reynolds stress and large-scale zonal flow production in the
      E*B driven hydrodynamic spectral condensation. We show that Reynolds stress is
      generated effectively by anisotropic vorticity structures possessing collective
      tilt angle. The maximum amplitude of the tilt, the Reynolds stress, and the mean
      zonal flow production coincide with the transition time of the velocity field,
      indicating a key role of turbulence-induced Reynolds stress in the condensation
      of the flow. The analysis of the energy transfer between turbulence and zonal
      flow shows coherent oscillations with pi/2 phase delay, thus indicating a
      predator-prey-like interaction between zonal flow and turbulence. 

PMID- 25615203
TI  - Modeling relativistic soliton interactions in overdense plasmas: a perturbed
      nonlinear Schrodinger equation framework.
AB  - We investigate the dynamics of localized solutions of the relativistic cold-fluid
      plasma model in the small but finite amplitude limit, for slightly overcritical
      plasma density. Adopting a multiple scale analysis, we derive a perturbed
      nonlinear Schrodinger equation that describes the evolution of the envelope of
      circularly polarized electromagnetic field. Retaining terms up to fifth order in
      the small perturbation parameter, we derive a self-consistent framework for the
      description of the plasma response in the presence of localized electromagnetic
      field. The formalism is applied to standing electromagnetic soliton interactions
      and the results are validated by simulations of the full cold-fluid model. To
      lowest order, a cubic nonlinear Schrodinger equation with a focusing nonlinearity
      is recovered. Classical quasiparticle theory is used to obtain analytical
      estimates for the collision time and minimum distance of approach between
      solitons. For larger soliton amplitudes the inclusion of the fifth-order terms is
      essential for a qualitatively correct description of soliton interactions. The
      defocusing quintic nonlinearity leads to inelastic soliton collisions, while
      bound states of solitons do not persist under perturbations in the initial phase
      or amplitude. 

PMID- 25615204
TI  - Ion acoustic turbulence in a 100-A LaB6 hollow cathode.
AB  - The temporal fluctuations in the near plume of a 100-A LaB(6) hollow cathode are
      experimentally investigated. A probe array is employed to measure the amplitude
      and dispersion of axial modes in the plume, and these properties are examined
      parametrically as a function of cathode operating conditions. The onset of ion
      acoustic turbulence is observed at high current and is characterized by a power
      spectrum that exhibits a cutoff at low frequency and an inverse dependence on
      frequency at high values. The amplitude of the turbulence is found to decrease
      with flow rate but to depend nonmonotonically on discharge current. Estimates of
      the anomalous collision frequency based on experimental measurements indicate
      that the ion acoustic turbulence collision frequency can exceed the classical
      rate at high discharge current densities by nearly two orders of magnitude.

PMID- 25615205
TI  - Ultrafast high-power microwave window breakdown: nonlinear and postpulse effects.
AB  - The time- and space-dependent optical emissions of nanosecond high-power
      microwave discharges near a dielectric-air interface have been observed by
      nanosecond-response four-framing intensified-charged-coupled device cameras. The
      experimental observations indicate that plasma developed more intensely at the
      dielectric-air interface than at the free-space region with a higher electric
      field amplitude. A thin layer of intense light emission above the dielectric was
      observed after the microwave pulse. The mechanisms of the breakdown phenomena are
      analyzed by a three-dimensional electromagnetic-field modeling and a two
      dimensional electromagnetic particle-in-cell simulation, revealing the formation
      of a space-charge microwave sheath near the dielectric surface, accelerated by
      the normal components of the microwave field, significantly enhancing the local
      field amplitude and hence ionization near the dielectric surface. The nonlinear
      positive feedback of ionization, higher electron mobility, and ultraviolet-driven
      photoemission due to the elevated electron temperature are crucial for achieving
      the ultrafast discharge. Following the high-power microwave pulse, the sheath
      sustains a glow discharge until the sheath collapses. 

PMID- 25615206
TI  - Controlling the fast electron divergence in a solid target with multiple laser
      pulses.
AB  - Controlling the divergence of laser-driven fast electrons is compulsory to meet
      the ignition requirements in the fast ignition inertial fusion scheme. It was
      shown recently that using two consecutive laser pulses one can improve the
      electron-beam collimation. In this paper we propose an extension of this method
      by using a sequence of several laser pulses with a gradually increasing
      intensity. Profiling the laser-pulse intensity opens a possibility to transfer to
      the electron beam a larger energy while keeping its divergence under control. We
      present numerical simulations performed with a radiation hydrodynamic code
      coupled to a reduced kinetic module. Simulation with a sequence of three laser
      pulses shows that the proposed method allows one to improve the efficiency of the
      double pulse scheme at least by a factor of 2. This promises to provide an
      efficient energy transport in a dense matter by a collimated beam of fast
      electrons, which is relevant for many applications such as ion-beam sources and
      could present also an interest for fast ignition inertial fusion. 

PMID- 25615207
TI  - Characterization of deuterium clusters mixed with helium gas for an application
      in beam-target-fusion experiments.
AB  - We measured the average deuterium cluster size within a mixture of deuterium
      clusters and helium gas by detecting Rayleigh scattering signals. The average
      cluster size from the gas mixture was comparable to that from a pure deuterium
      gas when the total backing pressure and temperature of the gas mixture were the
      same as those of the pure deuterium gas. According to these measurements, the
      average size of deuterium clusters depends on the total pressure and not the
      partial pressure of deuterium in the gas mixture. To characterize the cluster
      source size further, a Faraday cup was used to measure the average kinetic energy
      of the ions resulting from Coulomb explosion of deuterium clusters upon
      irradiation by an intense ultrashort pulse. The deuterium ions indeed acquired a
      similar amount of energy from the mixture target, corroborating our measurements
      of the average cluster size. As the addition of helium atoms did not reduce the
      resulting ion kinetic energies, the reported results confirm the utility of using
      a known cluster source for beam-target-fusion experiments by introducing a
      secondary target gas. 

PMID- 25615208
TI  - Exceeding the leading spike intensity and fluence limits in backward Raman
      amplifiers.
AB  - The leading amplified spike in backward Raman amplifiers can reach nearly
      relativistic intensities before the saturation by the relativistic electron
      nonlinearity. The saturation sets an upper limit to the largest achievable
      leading spike intensity. It is shown here that this limit can be substantially
      exceeded by the initially subdominant spikes, which surprisingly outgrow the
      leading spike after its nonlinear saturation. Furthermore, an initially
      negligible group velocity dispersion of the amplified pulse in strongly
      undercritical plasma appears to be capable of delaying the longitudinal
      filamentation instability in the nonlinear saturation regime. This enables
      further amplification of the pulse to even larger output fluences. 

PMID- 25615209
TI  - Nonlinear wave collapse, shock, and breather formation in an electron
      magnetohydrodynamic plasma.
AB  - Low-frequency nonlinear wave dynamics is investigated in a two-dimensional
      inhomogeneous electron magnetohydrodynamic (EMHD) plasma in the presence of
      electron viscosity. In the long-wavelength limit, the dynamics of the wave is
      found to be governed by a novel nonlinear equation. The result of the moving
      frame nonlinear analysis is noteworthy, which shows that this nonlinear equation
      does have a breather solution and electron viscosity is responsible for the
      breather. A breather is a nonlinear wave in which energy accumulates in a
      localized and oscillatory manner. Analytical solution and time-dependent
      numerical simulation of this novel equation reveal the collapse of a soliton
      (localized pulse) into a weak noise shelf and formation of shocklike structures. 

PMID- 25615210
TI  - Simulations of beam-matter interaction experiments at the CERN HiRadMat facility
      and prospects of high-energy-density physics research.
AB  - In a recent publication [Schmidt et al., Phys. Plasmas 21, 080701 (2014)], we
      reported results on beam-target interaction experiments that have been carried
      out at the CERN HiRadMat (High Radiation to Materials) facility using extended
      solid copper cylindrical targets that were irradiated with a 440-GeV proton beam
      delivered by the Super Proton Synchrotron (SPS). On the one hand, these
      experiments confirmed the existence of hydrodynamic tunneling of the protons that
      leads to substantial increase in the range of the protons and the corresponding
      hadron shower in the target, a phenomenon predicted by our previous theoretical
      investigations [Tahir et al., Phys. Rev. ST Accel. Beams 25, 051003 (2012)]. On
      the other hand, these experiments demonstrated that the beam heated part of the
      target is severely damaged and is converted into different phases of high energy
      density (HED) matter, as suggested by our previous theoretical studies [Tahir et
      al., Phys. Rev. E 79, 046410 (2009)]. The latter confirms that the HiRadMat
      facility can be used to study HED physics. In the present paper, we give details
      of the numerical simulations carried out to understand the experimental
      measurements. These include the evolution of the physical parameters, for
      example, density, temperature, pressure, and the internal energy in the target,
      during and after the irradiation. This information is important in order to
      determine the region of the HED phase diagram that can be accessed in such
      experiments. These simulations have been done using the energy deposition code
      fluka and a two-dimensional hydrodynamic code, big2, iteratively.

PMID- 25615211
TI  - Angular melting scenarios in binary dusty-plasma Coulomb balls: magic versus
      normal clusters.
AB  - Molecular-dynamic simulations were performed in order to investigate the melting
      processes of isotropically confined binary systems. We considered two species of
      particles, which differ by their amount of electric charge. A Lindemann type of
      criterion was used to determine the angular melting temperature. We demonstrate
      that the magic-to-normal cluster transition can evolve in two distinct ways, that
      is, through a structural phase transition of the first order or via a smooth
      transition where an increase of the shells' width leads to a continuous
      decreasing mechanical stability of the system. Moreover, for large systems, we
      demonstrate that the internal cluster exerts a minor effect on the mechanical
      stability of the external shell. Furthermore, we show that highly symmetric
      configurations, such as those found for multiple ring structures, have large
      mechanical stability, i.e., high angular melting temperature. 

PMID- 25615212
TI  - Elastodynamic Green's function retrieval through single-sided Marchenko inverse
      scattering.
AB  - The solution of the inverse scattering problem for the one-dimensional
      Schrodinger equation is given by the Marchenko equation. Recently, a Marchenko
      type equation has been derived for three-dimensional (3D) acoustic wave fields,
      whose solution has been shown to recover the Green's functions from points within
      the medium to its exterior, using only single-sided scattered data. Here we
      extend this approach to 3D vectorial wave fields that satisfy the elastodynamic
      wave equation and recover Green's functions from points interior to an elastic,
      solid-state medium from purely external and one-sided measurements. The method is
      demonstrated in a solid-earth-like model to construct Green's functions using
      only subsurface sources, from earth-surface force and deformation sources and
      particle velocity and stress measurements. 

PMID- 25615213
TI  - Single-sided Marchenko focusing of compressional and shear waves.
AB  - In time-reversal acoustics, waves recorded at the boundary of a strongly
      scattering medium are sent back into the medium to focus at the original source
      position. This requires that the medium can be accessed from all sides. We
      discuss a focusing method for media that can be accessed from one side only. We
      show how complex focusing functions, emitted from the top surface into the
      medium, cause independent foci for compressional and shear waves. The focused
      fields are isotropic and act as independent virtual sources for these wave types
      inside the medium. We foresee important applications in nondestructive testing of
      construction materials and seismological monitoring of processes inside the
      Earth. 

PMID- 25615214
TI  - Ultrashort optical waveguide excitations in uniaxial silica fibers: elastic
      collision scenarios.
AB  - In this work, we investigate the dynamics of an uniaxial silica fiber under the
      viewpoint of propagation of ultimately ultrashort optical waveguide channels. As
      a result, we unveil the existence of three typical kinds of ultrabroadband
      excitations whose profiles strongly depend upon their angular momenta. Looking
      forward to surveying their scattering features, we unearth some underlying head
      on scenarios of elastic collisions. Accordingly, we address some useful and
      straightforward applications in nonlinear optics through secured data
      transmission systems, as well as laser physics and soliton theory with optical
      soliton dynamics. 

PMID- 25615215
TI  - Bright solitons in nonlinear media with a self-defocusing double-well
      nonlinearity.
AB  - We show that stable bright solitons can appear in a medium with spatially
      inhomogeneous self-defocusing (SDF) nonlinearity of a double-well structure. For
      a specific choice of the nonlinearity parameters, we obtain exact analytical
      solutions for the fundamental bright solitons. By making use of the linear
      stability analysis, the stability region in the parameter space for the exact
      fundamental bright soliton is obtained numerically. We also show the bifurcation
      from an antisymmetric to an asymmetric bright soliton for the SDF double-well
      nonlinearity. 

PMID- 25615216
TI  - Bubble evolution and properties in homogeneous nucleation simulations.
AB  - We analyze the properties of naturally formed nanobubbles in Lennard-Jones
      molecular dynamics simulations of liquid-to-vapor nucleation in the boiling and
      the cavitation regimes. The large computational volumes provide a realistic
      environment at unchanging average temperature and liquid pressure, which allows
      us to accurately measure properties of bubbles from their inception as stable,
      critically sized bubbles, to their continued growth into the constant speed
      regime. Bubble gas densities are up to 50% lower than the equilibrium vapor
      densities at the liquid temperature, yet quite close to the gas equilibrium
      density at the lower gas temperatures measured in the simulations: The latent
      heat of transformation results in bubble gas temperatures up to 25% below those
      of the surrounding bulk liquid. In the case of rapid bubble growth-typical for
      the cavitation regime-compression of the liquid outside the bubble leads to local
      temperature increases of up to 5%, likely significant enough to alter the surface
      tension as well as the local viscosity. The liquid-vapor bubble interface is
      thinner than expected from planar coexistence simulations by up to 50%. Bubbles
      near the critical size are extremely nonspherical, yet they quickly become
      spherical as they grow. The Rayleigh-Plesset description of bubble-growth gives
      good agreement in the cavitation regime. 

PMID- 25615217
TI  - Spectral-domain-based scattering analysis of fields radiated by distributed
      sources in planar-stratified environments with arbitrarily anisotropic layers.
AB  - We discuss the numerically stable, spectral-domain computation and extraction of
      the scattered electromagnetic field excited by distributed sources embedded in
      planar-layered environments, where each layer may exhibit arbitrary and
      independent electrical and magnetic anisotropic response and loss profiles. This
      stands in contrast to many standard spectral-domain algorithms that are
      restricted to computing the fields radiated by Hertzian dipole sources in planar
      layered environments where the media possess azimuthal-symmetric material tensors
      (i.e., isotropic, and certain classes of uniaxial, media). Although computing the
      scattered field, particularly when due to distributed sources, appears (from the
      analytical perspective, at least) relatively straightforward, different
      procedures within the computation chain, if not treated carefully, are inherently
      susceptible to numerical instabilities and (or) accuracy limitations due to the
      potential manifestation of numerically overflown and (or) numerically unbalanced
      terms entering the chain. Therefore, primary emphasis herein is given to
      effecting these tasks in a numerically stable and robust manner for all ranges of
      physical parameters. After discussing the causes behind, and means to mitigate,
      these sources of numerical instability, we validate the algorithm's performance
      against closed-form solutions. Finally, we validate and illustrate the
      applicability of the proposed algorithm in case studies concerning active remote
      sensing of marine hydrocarbon reserves embedded deep within lossy, planar-layered
      media. 

PMID- 25615218
TI  - Influence of electrical boundary conditions on molecular dynamics simulations of
      ionic liquid electrosprays.
AB  - Molecular dynamics (MD) simulations are coupled to solutions of Poisson's
      equation to study the effects of the electrical boundary conditions on the
      emission modes of an electrospray thruster fed with an ionic liquid. A comparison
      of a new tip boundary condition with an analytical model based on a
      semihyperboloidal shape offers good agreement, although the analytical model
      overestimates the maximum value of the tangential electric field since it does
      not take into account the space charge that reduces the field at the liquid
      surface. It is found that a constant electric field model gives similar agreement
      to the more rigorous and computationally expensive tip boundary condition at
      lower flow rates. However, at higher mass flow rates the constant electric field
      produces extruded particles with higher Coulomb energy per ion, consistent with
      droplet formation. Furthermore, the MD simulations show that ion emission sites
      differ based on the boundary condition and snapshots offer an explanation as to
      why some boundary condition models will predict emission in a purely ionic mode,
      whereas others suggest a mixed ion-droplet regime. Finally, specific impulses and
      thrusts are compared for the different models and are found to vary up to 30% due
      to differences in the average charge to mass ratio. 

PMID- 25615219
TI  - Computing the Coulomb interaction in inhomogeneous dielectric media via a local
      electrostatics lattice algorithm.
AB  - The local approach to computing electrostatic interactions proposed by Maggs and
      adapted by Rottler and Pasichnyk for molecular-dynamics simulations is extended
      to situations where the dielectric background medium is inhomogeneous. We
      furthermore correct a problem of the original algorithm related to the correct
      treatment of the global dipole moment, provide an error estimate for the accuracy
      of the algorithm, and suggest a different form of the treatment of the self
      energy problem. Our implementation is highly scalable on many cores, and we have
      validated and compared its performance against theoretical predictions and
      simulation data obtained by other algorithmic approaches. 

PMID- 25615220
TI  - Simulation of counterflow pedestrian dynamics using spheropolygons.
AB  - Pedestrian dynamic models are typically designed for comfortable walking or
      slightly congested conditions and typically use a single disk or combination of
      three disks for the shape of a pedestrian. Under crowd conditions, a more
      accurate pedestrian shape has advantages over the traditional single or three
      disks model. We developed a method for simulating pedestrian dynamics in a large
      dense crowd of spheropolygons adapted to the cross section of the chest and arms
      of a pedestrian. Our numerical model calculates pedestrian motion from Newton's
      second law, taking into account viscoelastic contact forces, contact friction,
      and ground-reaction forces. Ground-reaction torque was taken to arise solely from
      the pedestrians' orientation toward their preferred destination. Simulations of
      counterflow pedestrians dynamics in corridors were used to gain insight into a
      tragic incident at the Madrid Arena pavilion in Spain, where five girls were
      crushed to death. The incident took place at a Halloween Celebration in 2012, in
      a long, densely crowded hallway used as entrance and exit at the same time. Our
      simulations reconstruct the mechanism of clogging in the hallway. The
      hypothetical case of a total evacuation order was also investigated. The results
      highlights the importance of the pedestrians' density and the effect of
      counterflow in the onset of avalanches and clogging and provides an estimation of
      the number of injuries based on a calculation of the contact-force network
      between the pedestrians. 

PMID- 25615221
TI  - Bloch mode synthesis: ultrafast methodology for elastic band-structure
      calculations.
AB  - We present a methodology for fast band-structure calculations that is generally
      applicable to problems of elastic wave propagation in periodic media. The
      methodology, called Bloch mode synthesis, represents an extension of component
      mode synthesis, a set of substructuring techniques originally developed for
      structural dynamics analysis. In Bloch mode synthesis, the unit cell is divided
      into interior and boundary degrees-of-freedom, which are described, respectively,
      by a set of normal modes and a set of constraint modes. A combination of these
      mode sets then forms a reduced basis for the band structure eigenvalue problem.
      The reduction is demonstrated on a phononic-crystal model and a locally resonant
      elastic-metamaterial model and is shown to accurately predict the frequencies and
      Bloch mode shapes with a dramatic decrease in computation time in excess of two
      orders of magnitude. 

PMID- 25615222
TI  - Numerical optimization using flow equations.
AB  - We develop a method for multidimensional optimization using flow equations. This
      method is based on homotopy continuation in combination with a maximum entropy
      approach. Extrema of the optimizing functional correspond to fixed points of the
      flow equation. While ideas based on Bayesian inference such as the maximum
      entropy method always depend on a prior probability, the additional step in our
      approach is to perform a continuous update of the prior during the homotopy flow.
      The prior probability thus enters the flow equation only as an initial condition.
      We demonstrate the applicability of this optimization method for two paradigmatic
      problems in theoretical condensed matter physics: numerical analytic continuation
      from imaginary to real frequencies and finding (variational) ground states of
      frustrated (quantum) Ising models with random or long-range antiferromagnetic
      interactions. 

PMID- 25615223
TI  - Renyi information flow in the Ising model with single-spin dynamics.
AB  - The n-index Renyi mutual information and transfer entropies for the two
      dimensional kinetic Ising model with arbitrary single-spin dynamics in the
      thermodynamic limit are derived as functions of ensemble averages of observables
      and spin-flip probabilities. Cluster Monte Carlo algorithms with different
      dynamics from the single-spin dynamics are thus applicable to estimate the
      transfer entropies. By means of Monte Carlo simulations with the Wolff algorithm,
      we calculate the information flows in the Ising model with the Metropolis
      dynamics and the Glauber dynamics, respectively. We find that not only the global
      Renyi transfer entropy, but also the pairwise Renyi transfer entropy, peaks in
      the disorder phase. 

PMID- 25615224
TI  - Numerical solutions of the Schrodinger equation with source terms or time
      dependent potentials.
AB  - We develop an approach to solving numerically the time-dependent Schrodinger
      equation when it includes source terms and time-dependent potentials. The
      approach is based on the generalized Crank-Nicolson method supplemented with an
      Euler-MacLaurin expansion for the time-integrated nonhomogeneous term. By
      comparing the numerical results with exact solutions of analytically solvable
      models, we find that the method leads to precision comparable to that of the
      generalized Crank-Nicolson method applied to homogeneous equations. Furthermore,
      the systematic increase in precision generally permits making estimates of the
      error. 

PMID- 25615225
TI  - Basis of symmetric polynomials for many-boson light-front wave functions.
AB  - We provide an algorithm for the construction of orthonormal multivariate
      polynomials that are symmetric with respect to the interchange of any two
      coordinates on the unit hypercube and are constrained to the hyperplane where the
      sum of the coordinates is one. These polynomials form a basis for the expansion
      of bosonic light-front momentum-space wave functions, as functions of
      longitudinal momentum, where momentum conservation guarantees that the fractions
      are on the interval [0,1] and sum to one. This generalizes earlier work on three
      boson wave functions to wave functions for arbitrarily many identical bosons. A
      simple application in two-dimensional phi(4) theory illustrates the use of these
      polynomials.

PMID- 25615226
TI  - Phase-field-based lattice Boltzmann model for axisymmetric multiphase flows.
AB  - In this paper, a phase-field-based lattice Boltzmann (LB) model is proposed for
      axisymmetric multiphase flows. Modified equilibrium distribution functions and
      some source terms are properly added into the evolution equations such that
      multiphase flows in the axisymmetric coordinate system can be described.
      Different from previous axisymmetric LB multiphase models, the added source terms
      that arise from the axisymmetric effect contain no additional gradients, and
      therefore the present model is much simpler. Furthermore, through the Chapmann
      Enskog analysis, the axisymmetric Chan-Hilliard equation and Navier-Stokes
      equations can be exactly derived from the present model. The model is also able
      to deal with flows with density contrast. A variety of numerical experiments,
      including planar and curve interfaces, an elongation field, a static droplet, a
      droplet oscillation, breakup of a liquid thread, and dripping of a liquid droplet
      under gravity, have been conducted to test the proposed model. It is found that
      the present model can capture accurate interface and the numerical results of
      multiphase flows also agree well with the analytical solutions and/or available
      experimental data. 

PMID- 25615227
TI  - Multiscale temporal integrators for fluctuating hydrodynamics.
AB  - Following on our previous work [S. Delong, B. E. Griffith, E. Vanden-Eijnden, and
      A. Donev, Phys. Rev. E 87, 033302 (2013)], we develop temporal integrators for
      solving Langevin stochastic differential equations that arise in fluctuating
      hydrodynamics. Our simple predictor-corrector schemes add fluctuations to
      standard second-order deterministic solvers in a way that maintains second-order
      weak accuracy for linearized fluctuating hydrodynamics. We construct a general
      class of schemes and recommend two specific schemes: an explicit midpoint method
      and an implicit trapezoidal method. We also construct predictor-corrector methods
      for integrating the overdamped limit of systems of equations with a fast and slow
      variable in the limit of infinite separation of the fast and slow time scales. We
      propose using random finite differences to approximate some of the stochastic
      drift terms that arise because of the kinetic multiplicative noise in the
      limiting dynamics. We illustrate our integrators on two applications involving
      the development of giant nonequilibrium concentration fluctuations in diffusively
      mixing fluids. We first study the development of giant fluctuations in recent
      experiments performed in microgravity using an overdamped integrator. We then
      include the effects of gravity and find that we also need to include the effects
      of fluid inertia, which affects the dynamics of the concentration fluctuations
      greatly at small wave numbers.

PMID- 25615228
TI  - Lattice-switching Monte Carlo method for crystals of flexible molecules.
AB  - We discuss implementation of the lattice-switching Monte Carlo method (LSMC) as a
      binary sampling between two synchronized Markov chains exploring separated minima
      in the potential energy landscape. When expressed in this fashion, the
      generalization to more complex crystals is straightforward. We extend the LSMC
      method to a flexible model of linear alkanes, incorporating bond length and angle
      constraints. Within this model, we accurately locate a transition between two
      polymorphs of n-butane with increasing density, and suggest this as a benchmark
      problem for other free-energy methods. 

PMID- 25615229
TI  - Combining Kohn-Sham and orbital-free density-functional theory for Hugoniot
      calculations to extreme pressures.
AB  - The shock Hugoniot for lithium 6 deuteride ((6)LiD) was calculated via first
      principles using Kohn-Sham density-functional theory molecular dynamics (KSMD)
      for temperatures of 0.5-25 eV. The upper limit of 25 eV represents a practical
      limit where KSMD is no longer computationally feasible due to the number of
      electronic bands which are required to be populated. To push the Hugoniot
      calculations to higher temperatures we make use of orbital-free density
      functional theory molecular dynamics (OFMD). Thomas-Fermi-Dirac-based OFMD gives
      a poor description of the electronic structure at low temperatures so the initial
      state is not well defined. We propose a method of bootstrapping the Hugoniot from
      OFMD to the Hugoniot from KSMD between 10 and 20 eV, where the two methods are in
      agreement. The combination of KSMD and OFMD allows construction of a first
      principles Hugoniot from the initial state to 1000 eV. Theoretical shock
      compression results are in good agreement with available experimental data and
      exhibit the appropriate high-temperature limits. We show that a unified KSMD-OFMD
      Hugoniot can be used to assess the quality of the existing equation-of-state
      (EOS) models and inform better EOS models based on justifiable physics.

PMID- 25615230
TI  - Tricritical points in a Vicsek model of self-propelled particles with bounded
      confidence.
AB  - We study the orientational ordering in systems of self-propelled particles with
      selective interactions. To introduce the selectivity we augment the standard
      Vicsek model with a bounded-confidence collision rule: a given particle only
      aligns to neighbors who have directions quite similar to its own. Neighbors whose
      directions deviate more than a fixed restriction angle alpha are ignored. The
      collective dynamics of this system is studied by agent-based simulations and
      kinetic mean-field theory. We demonstrate that the reduction of the restriction
      angle leads to a critical noise amplitude decreasing monotonically with that
      angle, turning into a power law with exponent 3/2 for small angles. Moreover, for
      small system sizes we show that upon decreasing the restriction angle, the kind
      of the transition to polar collective motion changes from continuous to
      discontinuous. Thus, an apparent tricritical point with different scaling laws is
      identified and calculated analytically. We investigate the shifting and vanishing
      of this point due to the formation of density bands as the system size is
      increased. Agent-based simulations in small systems with large particle
      velocities show excellent agreement with the kinetic theory predictions. We also
      find that at very small interaction angles, the polar ordered phase becomes
      unstable with respect to the apolar phase. We derive analytical expressions for
      the dependence of the threshold noise on the restriction angle. We show that the
      mean-field kinetic theory also permits stationary nematic states below a
      restriction angle of 0.681pi. We calculate the critical noise, at which the
      disordered state bifurcates to a nematic state, and find that it is always
      smaller than the threshold noise for the transition from disorder to polar order.
      The disordered-nematic transition features two tricritical points: At low and
      high restriction angle, the transition is discontinuous but continuous at
      intermediate alpha. We generalize our results to systems that show fragmentation
      into more than two groups and obtain scaling laws for the transition lines and
      the corresponding tricritical points. A numerical method to evaluate the
      nonlinear Fredholm integral equation for the stationary distribution function is
      also presented. This method is shown to give excellent agreement with agent-based
      simulations, even in strongly ordered systems at noise values close to zero. 

PMID- 25615231
TI  - Computing physical properties with quantum Monte Carlo methods with statistical
      fluctuations independent of system size.
AB  - We show that the recently proposed correlated sampling without reweighting
      procedure extends the locality (asymptotic independence of the system size) of a
      physical property to the statistical fluctuations of its estimator. This makes
      the approach potentially vastly more efficient for computing space-localized
      properties in large systems compared with standard correlated methods. A proof is
      given for a large collection of noninteracting fragments. Calculations on
      hydrogen chains suggest that this behavior holds not only for systems displaying
      short-range correlations, but also for systems with long-range correlations. 

PMID- 25615232
TI  - Reexamination of the calculation of two-center, two-electron integrals over
      Slater-type orbitals. I. Coulomb and hybrid integrals.
AB  - In this paper, which constitutes the first part of the series, we consider
      calculation of two-center Coulomb and hybrid integrals over Slater-type orbitals.
      General formulas for these integrals are derived with no restrictions on the
      values of the quantum numbers and nonlinear parameters. Direct integration over
      the coordinates of one of the electrons leaves us with the set of overlaplike
      integrals which are evaluated by using two distinct methods. The first one is
      based on the transformation to the ellipsoidal coordinates system and the second
      utilizes a recursive scheme for consecutive increase of the angular momenta in
      the integrand. In both methods simple one-dimensional numerical integrations are
      used in order to avoid severe digital erosion connected with the straightforward
      use of the alternative analytical formulas. It is discussed that the numerical
      integration does not introduce a large computational overhead since the
      integrands are well-behaved functions, calculated recursively with decent speed.
      Special attention is paid to the numerical stability of the algorithms.
      Applicability of the resulting scheme over a large range of the nonlinear
      parameters is tested on examples of the most difficult integrals appearing in the
      actual calculations including, at most, 7i-type functions (l=6). 

PMID- 25615233
TI  - Reexamination of the calculation of two-center, two-electron integrals over
      Slater-type orbitals. II. Neumann expansion of the exchange integrals.
AB  - In this paper we consider the calculation of two-center exchange integrals over
      Slater-type orbitals (STOs). We apply the Neumann expansion of the Coulomb
      interaction potential and consider calculation of all basic quantities which
      appear in the resulting expression. Analytical closed-form equations for all
      auxiliary quantities have already been known but they suffer from large digital
      erosion when some of the parameters are large or small. We derive two
      differential equations which are obeyed by the most difficult basic integrals.
      Taking them as a starting point, useful series expansions for small parameter
      values or asymptotic expansions for large parameter values are systematically
      derived. The resulting expansions replace the corresponding analytical
      expressions when the latter introduce significant cancellations. Additionally, we
      reconsider numerical integration of some necessary quantities and present a new
      way to calculate the integrand with a controlled precision. All proposed methods
      are combined to lead to a general, stable algorithm. We perform extensive
      numerical tests of the introduced expressions to verify their validity and
      usefulness. Advances reported here provide methodology to compute two-electron
      exchange integrals over STOs for a broad range of the nonlinear parameters and
      large angular momenta. 

PMID- 25615234
TI  - A Gelatinases-targeting scFv-based Fusion Protein Shows Enhanced Antitumour
      Activity with Endostar against Hepatoma.
AB  - Gelatinases play important roles in tumour invasion and metastasis and are thus
      considered promising targets for cancer therapy. In this study, a new single
      chain variable fragment (scFv)-based fusion protein Fv-LDP, composed of the anti
      gelatinases scFv and lidamycin apoprotein (LDP), was prepared, and its
      combination with angiogenesis inhibitor Endostar was then investigated. The
      fusion protein Fv-LDP specifically bound to various tumour cells, and its binding
      capability to human pulmonary giant cell carcinoma (PG) cells was higher than
      that of LDP. Fv-LDP inhibited the expression and secretion of gelatinases and
      could be internalized into tumour cells via endocytosis. Fv-LDP also suppressed
      the growth of human hepatoma cells and murine hepatoma 22 transplanted in Kunming
      mice in various degrees. In addition, Endostar could enhance the synergistic or
      additive inhibition of Fv-LDP on the growth, migration or invasion of human
      hepatoma cells shown by a colony formation assay and a transwell-based migration
      or invasion assay, respectively. In vivo, Fv-LDP/Endostar combination showed a
      significantly synergistic effect on the growth of a human hepatoma xenograft,
      with an inhibition rate of 80.8% compared with the Fv-LDP (44.1%) or Endostar
      (8.9%)-treated group. The above-mentioned results indicate that the fusion
      protein Fv-LDP is effective against transplantable hepatoma in mice and human
      hepatoma xenografts in athymic mice. Moreover, Endostar can potentiate the
      inhibition effect of Fv-LDP on the growth of human hepatoma cells and xenografts.
      These data will provide a new combined strategy for improving the therapeutic
      efficacy of treatments for hepatoma or other gelatinase-overexpressing tumours. 

PMID- 25615235
TI  - A quality by design approach to understand formulation and process variability in
      pharmaceutical melt extrusion processes.
AB  - OBJECTIVES: In this study, the principles of quality by design (QbD) have been
      uniquely applied to a pharmaceutical melt extrusion process for an immediate
      release formulation with a low melting model drug, ibuprofen. METHODS: Two
      qualitative risk assessment tools - Fishbone diagram and failure mode effect
      analysis - were utilized to strategically narrow down the most influential
      parameters. Selected variables were further assessed using a Plackett-Burman
      screening study, which was upgraded to a response surface design consisting of
      the critical factors to study the interactions between the study variables. In
      process torque, glass transition temperature (Tg ) of the extrudates, assay,
      dissolution and phase change were measured as responses to evaluate the critical
      quality attributes (CQAs) of the extrudates. The effect of each study variable on
      the measured responses was analysed using multiple regression for the screening
      design and partial least squares for the optimization design. KEY FINDINGS:
      Experimental limits for formulation and process parameters to attain optimum
      processing have been outlined. A design space plot describing the domain of
      experimental variables within which the CQAs remained unchanged was developed.
      CONCLUSIONS: A comprehensive approach for melt extrusion product development
      based on the QbD methodology has been demonstrated. Drug loading concentrations
      between 40- 48%w/w and extrusion temperature in the range of 90-130 degrees C
      were found to be the most optimum.

PMID- 25615238
TI  - Computational study of metal free alcohol dehydrogenation employing frustrated
      lewis pairs.
AB  - The catalysis of acceptorless alcohol dehydrogenation (AAD) is an important area
      of research. Transition metal-based systems are known to be effective catalysts
      for this reaction, but developing metal free catalytic systems would lead to
      highly desirable cheaper and greener alternatives. With this in mind, this
      computational study investigates design strategies than can lead to metal free
      frustrated Lewis pairs (FLPs) that can be employed for AAD catalysis. A careful
      study of 36 different proposed FLP candidates reveals that several new FLPs can
      be designed from existing, experimentally synthesized FLPs that can rival or be
      even better than state-of-the-art transition metal-based systems in catalyzing
      the alcohol dehydrogenation process. 

PMID- 25615236
TI  - Modulating antibacterial immunity via bacterial membrane-coated nanoparticles.
AB  - Synthetic nanoparticles coated with cellular membranes have been increasingly
      explored to harness natural cell functions toward the development of novel
      therapeutic strategies. Herein, we report on a unique bacterial membrane-coated
      nanoparticle system as a new and exciting antibacterial vaccine. Using
      Escherichia coli as a model pathogen, we collect bacterial outer membrane
      vesicles (OMVs) and successfully coat them onto small gold nanoparticles (AuNPs)
      with a diameter of 30 nm. The resulting bacterial membrane-coated AuNPs (BM
      AuNPs) show markedly enhanced stability in biological buffer solutions. When
      injected subcutaneously, the BM-AuNPs induce rapid activation and maturation of
      dendritic cells in the lymph nodes of the vaccinated mice. In addition,
      vaccination with BM-AuNPs generates antibody responses that are durable and of
      higher avidity than those elicited by OMVs only. The BM-AuNPs also induce an
      elevated production of interferon gamma (INFgamma) and interleukin-17 (IL-17),
      but not interleukin-4 (IL-4), indicating its capability of generating strong Th1
      and Th17 biased cell responses against the source bacteria. These observed
      results demonstrate that using natural bacterial membranes to coat synthetic
      nanoparticles holds great promise for designing effective antibacterial vaccines.

PMID- 25615237
TI  - Inpatient rehabilitation outcomes in patients with malignant spinal cord
      compression compared to other non-traumatic spinal cord injury: A population
      based study.
AB  - OBJECTIVE: To compare and describe demographic characteristics, clinical, and
      survival outcomes in patients admitted for inpatient rehabilitation following
      malignant spinal cord compression (MSCC) or other causes of non-traumatic spinal
      cord injury (NT-SCI). DESIGN: A retrospective cohort design was employed, using
      data retrieved from administrative databases. SETTING: Rehabilitation facilities
      or designated rehabilitation beds in Ontario, Canada, from April 2007 to March
      2011. PARTICIPANTS: Patients with incident diagnoses of MSCC (N = 143) or NT-SCI
      (N = 1,274) admitted for inpatient rehabilitation. OUTCOME MEASURES: Demographic,
      impairment, functional outcome (as defined by the Functional Independence Measure
      (FIM)), discharge, healthcare utilization, survival, and tumor characteristics.
      RESULTS: There was a significant improvement in the FIM from admission to
      discharge (mean change 20.1 +/- 14.3, <0.001) in the MSCC cohort. NT-SCI patients
      demonstrated a higher FIM efficiency (1.2 +/- 1.7 vs. 0.8 +/- 0.8, <0.001) and
      higher total (24.0 +/- 14.4 vs. 20.1 +/- 14.3, <0.001) FIM gains relative to MSCC
      cases. However, there were no differences between the MSCC and NT-SCI cohorts in
      length of stay (34.6 +/- 30.3 vs. 37.5 +/- 35.2, P = 0.8) or discharge FIM (100.7
      +/- 19.6 vs. 103.3 +/- 18.1, P = 0.1). Three-month, 1-year, and 3-year survival
      rates in the MSCC and NT-SCI cohorts were 76.2% vs. 97.6%, 46.2% vs. 93.7%, and
      27.3% vs. 86.7%, respectively. The majority (65.0%) of patients with MSCC was
      discharged home and met their rehabilitation goals (75.5%) at comparable rates to
      patients with NT-SCI (69.7 and 81.3%). CONCLUSION: Despite compromised survival,
      patients with MSCC make clinically significant functional gains and exhibit
      favorable discharge outcomes following inpatient rehabilitation. Current
      administrative data suggests the design and scope of inpatient rehabilitation
      services should reflect the unique survival-related prognostic factors in
      patients with MSCC.

PMID- 25615239
TI  - Sexual stereotypes in medicine.

PMID- 25615240
TI  - The importance of the gubernaculum in testicular migration during the human fetal
      period.
AB  - OBJECTIVES: The objective of this review is to study the role of the gubernaculum
      in the testicular migration process during the human fetal period. MATERIALS AND
      METHODS: We performed a descriptive review of the literature about the role of
      the gubernaculum in testicular migration during the human fetal period. RESULTS:
      In the first phase of testicular migration, the gubernaculum enlarges to hold the
      testis near the groin and in the second phase the gubernaculum migrates across
      the pubic region to reach the scrotum. The proximal portion of the gubernaculum
      is attached to the testis and epididymis and the presence of multiple insertions
      in the distal gubernaculum is extremely rare. The presence of muscle and nerves
      in the human gubernaculum is very poor. The gubernaculum of patients with
      cryptorchidism has more fibrous tissue and less collagen and when the patients
      are submitted to hormonal treatment, the gubernaculum components alter
      significantly. CONCLUSIONS: The gubernaculum presents significant structural
      modifications during testicular migration in human fetuses.

PMID- 25615241
TI  - Brazilian abstracts presented at the American Urological Association annual
      meetings: contribution, publication rates, and comparison with oncology
      abstracts.
AB  - PURPOSE: Scientific research originating from Brazil appears to be rising in
      several medical fields. Research results are often presented at scientific
      meetings before publication in peer-reviewed journals. We investigated the
      publication rate of Brazilian studies presented in American Urological
      Association (AUA) meetings and compared with the rate of publication of Brazilian
      oncological studies presented at the American Society of Clinical Oncology (ASCO)
      meetings. MATERIALS AND METHODS: a hand search of 12,454 abstracts presented at
      aua meetings 2001-2007 was conducted. abstracts for which at least two-thirds of
      institutions were from brazil were considered as brazilian. final publication was
      searched in pubmed and lilacs databases. oncological abstracts were also hand
      searched in the asco meetings proceedings in the same years. RESULTS: There was
      no significant temporal trend in the proportion of AUA studies originating from
      Brazil along those 7 years. A total of 195 abstracts (1.57%) were from Brazil.
      One hundred (51.3%) abstracts were published in full, and the estimated 5-year
      publication rate was 48.2%. There was a progressive increase in publication rates
      for studies categorized as video, poster, and podium presentations. Considering
      abstracts presented in years 2001-2005, urologic publication rate was
      significantly higher than for abstracts presented at the ASCO meeting.
      CONCLUSIONS: Our results suggest that the Brazilian contribution to AUA meetings
      is at a plateau and that the Brazilian literature contribution is greater in
      urology than in oncology. Efforts must be invested towards raising this plateau
      and understanding qualitative aspects of the urology scientific output from
      Brazil.

PMID- 25615242
TI  - Epidemiological study of penile cancer in Pernambuco: experience of two reference
      centers.
AB  - OBJECTIVES: To investigate and analyze the epidemiological profile of penile
      cancer in the state of Pernambuco and compare this information with other studies
      related to the issue. MATERIAL AND METHODS: We conducted a retrospective,
      observational and descriptive study of all patients with penile cancer in two
      reference centers in Pernambuco - Brazil, from 2007 to 2012. The variables
      studied were: age, region from the state, socio-economic situation, previous
      postectomy, smoking, time from the beginning of injury to diagnosis, staging of
      the primary lesion, tumor differentiation, treatment performed and death due to
      cancer. RESULTS: The total number of patients was 88. The highest prevalence was
      seen in those aged between 66 and 75 years. About the socio-economic situation,
      67% worked informally and 64.8% received up to two minimum wages. Of all
      patients, 57% were married and 50% illiterate. The Metropolitan Region of Recife
      was the one with the highest number of cases, 41%. Tobacco smoking was reported
      in 48.9% of cases and prior postectomy in 3.4%. Most often it was observed an
      average period of six months from the onset of symptoms to diagnosis. And when
      the lesion was diagnosed, it usually had 2 to 5 cm (64.7%), stage T2 in 50% and
      well differentiated in 79.6%. Partial penectomy was performed in 76.1% and total
      in 17%. Death was observed in 27.3%. CONCLUSION: The clinical profile and
      epidemiological characteristics found in this study are similar to other national
      and international studies related to the issue, i.e., typical of underdeveloped
      or developing countries.

PMID- 25615243
TI  - Prostate-specific antigen testing in men between 40 and 70 years in Brazil:
      database from a check-up program.
AB  - OBJECTIVES: To evaluate the PSA in a large population of Brazilian men undergone
      to check up, and correlate the PSA cutoffs with prostate size and urinary
      symptoms. MATERIALS AND METHODS: This is a cross sectional study performed with
      men between 40 and 70 years undergone to check-up. All men were undergone to
      urological evaluation, digital rectal examination, prostate-specific antigen, and
      ultrasonography The exclusion criteria were men who used testosterone in the last
      six months, or who were using 5 alpha-reductase inhibitors. RESULTS: A total of
      5015 men with an average age of 49.0 years completed the study. Most men were
      white and asymptomatic. The PSA in the three different aging groups were 0.9 +/-
      0.7 ng/dL for men between 40 and 50; 1.2 +/- 0.5 ng/dL for men between 50 and 60;
      and 1.7 +/- 1.5 ng/dL for men greater than 60 years (p=0.001). A total of 192 men
      had PSA between 2.5 and 4 ng/ml. From these men 130 were undergone to prostate
      biopsy. The predictive positive value of biopsy was 25% (32/130). In the same
      way, 100 patients had PSA > 4 ng/mL. From these men, 80 were undergone to
      prostate biopsy. In this group, the predictive positive value of biopsy was 40%
      (32/100). The Gleason score was 6 in 19 men (60%), 7 in 10 men (31%) and 8 in 3
      men (9%). CONCLUSIONS: The PSA level of Brazilian men undergone to check up was
      low. There was a positive correlation with aging, IPSS and prostate size.

PMID- 25615244
TI  - Preoperative serum albumin as a prognostic factor in patients with upper urinary
      tract urothelial carcinoma.
AB  - PURPOSE: The study evaluated whether preoperative measures of the C-reactive
      protein-systemic inflammatory response may predict cancer survival independent of
      tumor stage in patients with upper urinary tract urothelial carcinoma (UTUC).
      MATERIALS AND METHODS: Between September 1999 and October 2010, 181 patients
      submitted to radical nephroureterectomy were available for evaluation.
      Multivariate survival analyses were performed using Cox's proportional hazards
      model and the coefficient for each factor was divided by the highest coefficient,
      multiplied by 4, and rounded to the nearest integer. RESULTS: Multivariate
      analyses showed that tumor location, pathologic T stage, lymphovascular invasion,
      margin status, and albumin level were independent contributors. The bootstrap
      corrected C statistics of the model were 0.813 for disease-specific survival and
      0.755 for overall survival, respectively. For time to disease-specific and
      overall mortality for patients, integrated area under the curve values were 0.792
      and 0.739, respectively. When patients were clustered into three groups according
      to their model-predicted survival, the 5-year disease-specific survival in the
      low-, intermediate- and high-risk group was 95.4%, 76.2%, and 36.9%, respectively
      (p<0.001), and were 87.8%, 54.4%, and 31.8%, respectively, for overall survival
      (p<0.001). Decision curve analysis revealed that the use of model was associated
      with net benefit gains relative to the treat-all strategy. CONCLUSIONS:
      Pretreatment albumin is a simple biomarker based on routinely available well
      standardized measures, and is not an expensive and time-consuming process.
      Hypoalbuminemia is an independent marker of poor prognosis in patients with upper
      urinary tract urothelial carcinoma.

PMID- 25615245
TI  - What is the incidence of kidney stones after chemotherapy in patients with
      lymphoproliferative or myeloproliferative disorders?
AB  - INTRODUCTION: This study describes the incidence and risk factors of de novo
      nephrolithiasis among patients with lymphoproliferative or myeloproliferative
      diseases who have undergone chemotherapy. MATERIALS AND METHODS: From 2001 to
      2011, patients with lymphoproliferative or myeloproliferative disorders treated
      with chemotherapy were retrospectively identified. The incidence of image proven
      nephrolithiasis after chemotherapy was determined. Demographic and clinical
      variables were recorded. Patients with a history of nephrolithiasis prior to
      chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis,
      and secondary outcomes were risk factors predictive of de novo stone. Comparative
      statistics were used to compare demographic and disease specific variables for
      patients who developed de novo stones versus those who did not. RESULTS: A total
      of 1,316 patients were identified and the incidence of de novo nephrolithiasis
      was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with
      nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had
      myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH
      was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels
      were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean
      uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were
      higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and
      hyperlipidemia (p<0.001) were more common in stone formers. In multivariate
      analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone.
      CONCLUSIONS: We report the incidence of de novo nephrolithiasis in patients who
      have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia
      are patient-specific risk factors that increase the odds of developing an upper
      tract stone following chemotherapy.

PMID- 25615246
TI  - A transobturator adjustable system for male incontinence: 30-month follow-up of a
      multicenter study.
AB  - PURPOSE: To report long-term results of the Argus T adjustable system for
      treatment of post-prostatectomy urinary incontinence (PPI). MATERIALS AND
      METHODS: From October 2007 to August 2008, 37 patients with PPI were included in
      a prospective, single-arm, multicenter trial of treatment with the Argus T
      adjustable system (Promedon, Argentina). Preoperative evaluation included urine
      culture, urethrocystoscopy, urodynamic testing, 24-h pad weight test (PWT) and
      quality of life questionnaires. Patients were stratified according to baseline
      degree of incontinence (mild-moderate or severe). Postoperative evaluation
      included immediate PWT, quality of life questionnaires and daily use of pads at
      1, 12 and 30 months. RESULTS AND CONCLUSIONS: One patient was lost to follow-up.
      At the 30-month follow-up, 24/31 patients (77%) were dry, 3/31 (10%) improved and
      4/31 (13%) were failures. In particular, in the mild-moderate group, 8/8 (100%)
      patients were dry. In the severe group, 20/28 patients (71%) were dry, 3/28 (11%)
      improved and 5/28 (18%) were failures. Median visual analogue scale (VAS) scores
      dropped from 9 (4-10) to 0.5 (0-10) and International Consultation on
      Incontinence Questionnaire Short Form scores from (ICIQ-SF) 19 (12-21) to 1 (0
      10). Retrograde leak point pressure increased from 18 (5-29) to 35 (22-45) cm H2O
      after intraoperative adjustment. Complications included immediate postoperative
      infection in 2/36 patients (6%) and transient inguinal and/or perineal pain in
      22/36 patients (61%). Argus T has a long-term high success rate (86% cure +
      improvement at the 30-month follow-up). Good outcomes were achieved even in
      severe incontinence cases and maintained for over 30 months.

PMID- 25615247
TI  - One hundred cases of SUI treatment that failed: a prospective observational study
      on the behavior of patients after surgical failure.
AB  - OBJECTIVES: Determine what happens to patients after unsuccessful SUI operations
      and to explore the reasons why these patients change doctors. MATERIALS AND
      METHODS: One hundred consecutive failed patients treated for SUI were interviewed
      about the exams requested after persistence of the incontinence as well as the
      reasons they abandoned their primary doctors through a structured questionnaire.
      RESULTS: Among the patients with cases of anterior colporrhaphy, bladder
      suspensions or slings, 34.3%, 13.7% and 8.3%, respectively, were not offered any
      further type of investigative procedures to clarify the failure. Urodynamic
      evaluations were recommended in 75% of failed slings, and 66.6% of the patients
      proceeded with these tests. In contrast, only 31% of patients with bladder
      suspensions and 40% of patients with anterior colporrhaphy were recommended for
      urodynamic investigations, and only 44.4% and 28.5% of them, respectively,
      proceeded with the option. Patients' delusions were reinforced by the doctors'
      attitude toward the investigations. Vacuous justifications and the lack of
      intention to seek improvement were the driving forces causing the patients to
      change doctors. CONCLUSION: Unsuccessful patients are evaluated in a non-protocol
      form. Difficulty in clarifying the reasons for surgical failure and the
      disruption of the doctor-patient relationship are the main reasons why patients
      abandon them.

PMID- 25615248
TI  - Patients lost to follow-up after midurethral sling surgery: how are they?
AB  - PURPOSE: To assess the ratio of patients lost to follow-up (FU) after midurethral
      sling surgery, to evaluate their success rate and current status, and to identify
      the reasons for FU loss. MATERIALS AND METHODS: Two-hundred thirty-eight patients
      who received trans-obturator tape (TOT) surgery were reviewed. For patients lost
      to FU within 3 months, Stamey's outcome questionnaire and questions regarding the
      reasons for FU loss were submitted via phone interview. RESULTS: One hundred
      forty-three (60.1%) patients (FU loss group) were lost to FU within 3 months
      postoperatively. In the FU loss group, phone interviews were conducted with 117
      (81.8%) patients. Aside from the urgency rate (59.3% vs. 72.3%, p=0.049), there
      were no significant statistical differences in preoperative profiles between two
      group. The success rate of the FU loss group (80.3%, 94 of 117 patients) was
      lower than that of the FU group (95.8%, 91 of 95 patients) (p=0.001). The success
      rates in the FU loss group with mixed urinary incontinence (MUI) were
      significantly lower than in the FU group with MUI. As for the reason for FU loss,
      74 patients (62.7%) were lost due to incontinence improvement, 19 patients
      (16.1%) cited personal problems, and 5 patients forgot the next follow-up date.
      Only 10 patients gave up further treatment despite their persisting incontinence.
      CONCLUSIONS: In our study, more than half of patients were lost to follow-up
      after midurethral sling surgery. The FU loss group showed a lower surgical
      success rate, particularly with MUI. Close FU is recommended for better
      consultation of patients ' incontinence.

PMID- 25615249
TI  - Robotic repair of vesicovaginal fistulae with the transperitoneal-transvaginal
      approach: a case series.
AB  - OBJECTIVE: To describe a novel technique of repairing the VVF using the
      transperitoneal-transvaginal approach. MATERIALS AND METHODS: From June 2011 to
      October 2013, four patients with symptoms of urine leakage in the vagina
      underwent robotic repair of VVF with the transperitoneal-transvaginal approach.
      Cystoscopy revealed the fistula opening on the bladder. A ureteral stent was
      placed through the fistulous tract. After trocar placement, the omental flap was
      prepared and mobilized robotically. The vagina was identified and incised. The
      fistulous tract was excised. Cystorrhaphy was performed in two layers in an
      interrupted fashion. The vaginal opening was closed with running stitches. The
      omentum was interposed and anchored between the bladder and vagina. Finally, the
      ureteral catheters were removed in case they have been placed, and an 18 Fr
      urethral catheter was removed on the 14th postoperative day. RESULTS: The mean
      age was 46 years (range: 41 to 52 years). The mean fistula diameter was 1.5 cm
      (range 0.3 to 2 cm). The mean operative time was 117.5 min (range: 100 to 150
      min). The estimated blood loss was 100 mL (range: 50 to 150 mL). The mean
      hospital stay was 1.75 days (range: 1 to 3 days). The mean Foley catheter
      duration was 15.75 days (range: 10 to 25 days). There was no evidence of
      recurrence in any of the cases. CONCLUSIONS: The robot-assisted laparoscopic
      transperitoneal transvaginal approach for VVF is a feasible procedure when the
      fistula tract is identified by first intentionally opening the vagina, thereby
      minimizing the bladder incision and with low morbidity.

PMID- 25615250
TI  - Relationship between kidney volume and body indexes in the Turkish population
      determined using ultrasonography.
AB  - OBJECTIVE: To estimate the kidney volume of the healthy Turkish population using
      ultrasound and to evaluate the relationship between kidney volume and body
      indexes. MATERIALS AND METHODS: Kidney ultrasound evaluation was performed on 152
      patients (mean age: 42 +/- 13.7 years). Kidney length, width and thickness were
      measured using ultrasound. Mean total and parenchymal volume were also
      calculated. Patients' age, sex, weight, height and body mass index (BMI) (kg/m2)
      were recorded. RESULTS: According to ultrasound, kidney lengths were 10.3 +/- 7.8
      cm for the right and 10.4 +/- 9 cm for the left. Volumes were 158 +/- 39 cm3 for
      the right and 168 +/- 40 cm3 for the left. Volumes in women were 151.8 +/- 39 cm3
      for the right and 159.8 +/- 37 cm3 for the left, and 164.3 +/- 38 cm3 for the
      right and 175.8 +/- 41 cm3 for the left in men. Kidney measurements correlated
      with body height and weight. A strong correlation with total kidney volume and
      kidney measurements was determined for body weight for both kidneys (p<0.001). A
      significant correlation with kidney volume and width was determined for both
      kidneys (p<0.001). A positive correlation was also found between parenchymal and
      total kidney volume for both kidneys (p<0.001). CONCLUSION: The most significant
      factors associated with kidney volume for both kidneys in the Turkish population
      are kidney width and body weight. Measuring kidney volume with ultrasound is a
      feasible modality and is widely available for daily clinical practice.

PMID- 25615251
TI  - Difference between actual vs. pathology prostate weight in TURP and radical
      robotic-assisted prostatectomy specimen.
AB  - INTRODUCTION: To investigate and highlight the effect of formaldehyde induced
      weight reduction in transurethral resection of prostate (TURP) and radical
      robotically-assisted prostatectomy (RALP) specimen as a result of standard
      chemical fixation. MATERIALS AND METHODS: 51 patients were recruited from January
      2013 to June 2013 who either underwent a TURP (n=26) or RALP (n=25). Data was
      collected prospectively by the operating surgeon who measured the native, unfixed
      histology specimen directly after operation. The specimens were fixed in 10%
      Formaldehyde Solution BP and sent to the pathology laboratory where after
      sufficient fixation period was re-weighed. RESULTS: Overall mean age 64.78 years,
      TURP mean age 68.31 years RALP mean age 61.12 years. We found that the overall
      prostatic specimen (n=51) weight loss after fixation was a mean of 11.20% (3.78
      grams) (p <= 0.0001). Subgroup analysis of the native TURP chips mean weight was
      16.15 grams and formalin treated mean weight was 14.00 grams (p <= 0.0001).
      Therefore, TURP chips had a mean of 13.32 % (2.15 grams) weight loss during
      chemical fixation. RALP subgroup unfixed specimen mean weight was 52.08 grams and
      formalin treated mean weight was 42.60 grams (p <= 0.0001), a 19.32 % (9.48
      grams) mean weight reduction. CONCLUSION: It has not been known that prostatic
      chips and whole human radical prostatectomy specimen undergo a significant weight
      reduction. The practical significance of the accurate prostate weight in patient
      management may be limited, however, it is agreed that this should be recorded
      correctly, as data is potential interest for research purposes and vital for
      precise documentation.

PMID- 25615252
TI  - Efficacy of Pelvisoft(r) Biomesh for cystocele repair: assessment of long-term
      results.
AB  - INTRODUCTION AND HYPOTHESIS: To our knowledge a study regarding the efficacy of
      Pelvisoft(r) Biomesh for cystocele repair has not previously been reported in the
      literature. The aim of our study was to assess the long-term efficacy, subjective
      outcomes and complications in the use of a non-synthetic porcine skin mesh graft
      (Pelvisoft(r) Biomesh) associated with transvaginal anterior colporrhaphy in the
      treatment of cystocele prolapse. MATERIALS AND METHODS: A retrospective study was
      performed at a single centre. Thirty-three women aged 35-77 years underwent
      cystocele repair using Pelvisoft(r) graft between December 2005 and June 2009.
      Twenty-nine women who underwent transvaginal cystocele repair with Pelvisoft(r)
      Biomesh for over a 2 years period were assessed. Four patients were lost to
      follow-up. Cystocele repair was performed via the vaginal route using
      Pelvisoft(r) Biomesh implant by inserting it in the anterior vaginal wall.
      RESULTS: The median follow-up time was 54.0 months. The rate of recurrence was
      17.3%. A total of 6.9% of patients presented early mesh exposure treated by
      conservative treatment. The mean PFDI-20 score was 72.2. Among sexually active
      women, the mean PISQ 12 was 33.9 but 56.2% had dyspareunia. After surgery, 6
      patients had de novo intercourse. CONCLUSIONS: Our results show that the use of
      Pelvisoft(r) biomaterial associated with anterior colporrhaphy for cystocele
      repair appears to be safe with acceptable failure and complication rates at long
      term. Nevertheless, an adverse impact on sexual function was reported by the
      majority of patients.

PMID- 25615253
TI  - Activity and safety of sunitinib in poor risk metastatic renal cell carcinoma
      patients.
AB  - PURPOSE: To assess the activity, safety and treatment patterns of sunitinib in
      patients with poor-risk metastatic renal cell carcinoma (mRCC). MATERIALS AND
      METHODS: We retrospectively reviewed the charts of poor risk patients treated
      with sunitinib from October 2006 to July 2013 who met the eligibility criteria.
      The primary endpoint was overall survival (OS). Tumor radiological response was
      measured according to RECIST 1.1 and adverse events (AEs) were assessed through
      standard criteria. RESULTS: Median OS was 8.16 months (95% CI, 5.73-10.59). Of
      the 53 patients included in this analysis, 9 (17.0%) achieved partial response,
      12 (22.6%) had stable disease. Median treatment duration was 3.30 months (95% CI:
      1.96-4.63) and 26.4% of patients discontinued treatment due to toxicity. Grade 3
      or higher AEs occurred in 39.6% of patients, the most common being fatigue
      (15.1%), neutropenia (9.5%), nausea, vomiting and diarrhea (7.5% each).
      DISCUSSION: Sunitinib may benefit some unselected poor-risk patients, although
      the rates of AEs and drug discontinuation suggest a need for careful patient
      monitoring.

PMID- 25615254
TI  - New head-mounted display system applied to endoscopic management of upper urinary
      tract carcinomas.
AB  - PURPOSE: We tested a new head-mounted display (HMD) system for surgery on the
      upper urinary tract. SURGICAL TECHNIQUE: Four women and one man with abnormal
      findings in the renal pelvis on computed tomography and magnetic resonance
      imaging underwent surgery using this new system. A high definition HMD (Sony,
      Tokyo, Japan) is connected to a flexible ureteroscope (Olympus, Tokyo, Japan) and
      the images from the ureteroscope are delivered simultaneously to various
      participants wearing HMDs. Furthermore, various information in addition to that
      available through the endoscope, such as the narrow band image, the fluoroscope,
      input from a video camera mounted on the lead surgeon's HMD and the vital
      monitors can be viewed on each HMD. RESULTS: Median operative duration and
      anesthesia time were 53 and 111 minutes, respectively. The ureteroscopic
      procedures were successfully performed in all cases. There were no notable
      negative outcomes or incidents (Clavien-Dindo grade >= 1). CONCLUSION: The HMD
      system offers simultaneous, high-quality magnified imagery in front of the eyes,
      regardless of head position, to those participating in the endoscopic procedures.
      This affordable display system also provides various forms of information related
      to examinations and operations while allowing direct vision and navigated vision.

PMID- 25615255
TI  - Continuous renal replacement therapy in children with multiple organ dysfunction
      syndrome: a case series.
AB  - There is a lack of definitive information regarding the precise indications,
      implementation, and outcomes of continuous renal replacement therapy (CRRT) for
      the treatment of critically ill children. Six children (three boys, three girls)
      aged from 3 days to 8 years, all of whom had multiple organ failure, were
      submitted to bedside CRRT using M60 filter membranes. Modified Port carbonate
      formula was used and clotting time was maintained between 20 and 30 minutes.
      Activated partial thromboplastin time was 1.5- to 2-fold normal. One patient
      discontinued treatment due to family decision. Marked improvements were seen in
      the remaining five patients, including normalization of blood urea nitrogen and
      creatinine levels, stabilization of electrolytes, and improvements in markers of
      organ function. Of note, one patient (a six-year-old male) underwent the
      treatment for 241 hours. All five patients were subsequently discharged and
      recovered uneventfully. CRRT is effective for the management of children who are
      critically ill due to multiple organ failure. 

PMID- 25615256
TI  - Extra corporeal shockwave lithotripsy resulting in skin burns--a report of two
      cases.
AB  - Severe skin injury after extracorporeal shock wave lithotripsy (ESWL) is rare. We
      describe two patients who suffered full thickness skin burns following ESWL for
      renal calculi. One patient was treated conservatively and the other underwent
      debridement with skin grafting. We speculate that failure of the thermostatic
      mechanism of the lithotripter, leading to overheating of the water-filled
      cushion, resulted in this very rare adverse event. Proper preoperative patient
      counseling regarding the risk of serious burn injuries will help to avoid
      potential litigation. 

PMID- 25615257
TI  - Pure laparoscopic augmentation ileocystoplasty.
AB  - INTRODUCTION: Guillain-Barre syndrome is an acute neuropathy that rarely
      compromises bladder function. Conservative management including clean
      intermittent catheterization and pharmacotherapy is the primary approach for
      hypocompliant contracted bladder. Surgical treatment may be used in refractory
      cases to improve bladder compliance and capacity in order to protect the upper
      urinary tract. We describe a case of pure laparoscopic augmentation
      ileocystoplasty in a patient affected by Guillain-Barre syndrome. PRESENTATION: A
      15-year-old female, complaining of voiding dysfunction, recurrent urinary tract
      infection and worsening renal function for three months. A previous history of
      Guillain-Barre syndrome on childhood was related. A voiding cystourethrography
      showed a pine-cone bladder with moderate post-void residual urine. The urodynamic
      demonstrated a hypocompliant bladder and small bladder capacity (190 mL) with
      high detrusor pressure (54 cmH2O). Nonsurgical treatments were attempted, however
      unsuccessfully.

PMID- 25615259
TI  - Self-aggregation of surfactant ethane-1,2-diyl bis(N,N-dimethyl-N
      hexadecylammoniumacetoxy) dichloride: tensiometric, microscopic, and
      spectroscopic studies.
AB  - We have investigated the effect of salt additives (NaCl, Na2SO4, Na3PO4, NaTos,
      and NaAn) on the aggregation behavior of a cleavable biodegradable ester-bonded
      dicationic gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N
      hexadecylammoniumacetoxy) dichloride (16-E2-16). A multitechnique approach
      employing tensiometry, fluorescence, proton magnetic resonance (1H NMR),
      transmission electron microscopy (TEM), absorption spectrophotometry (UV), and
      Fourier transform infrared spectroscopy (FTIR) was utilized to probe
      physicochemical fluctuations. Appreciable changes were observed in various
      physicochemical parameters, viz., critical micelle concentration (CMC), surface
      excess concentration (Gamma(max)), minimum area per headgroup (A(min)), free
      energy of micellization (DeltaG(mic) degrees ), free energy of adsorption
      (DeltaG(ads) degrees ), and aggregation number (N(agg)). Counter ions were found
      to affect through electrostatic and hydrophobic influence obeying the overall
      trend as NaAn > NaTos > Na3PO4 > Na2SO4 > NaCl. 1H NMR, TEM, UV, and FTIR results
      reveal microstructure evolution and phase transitions. These results thus provide
      deeper insights in understanding of self-aggregation and microstructure evolution
      of biocompatible (green) aqueous systems of the gemini surfactant and their
      implications in the biomedical and pharmaceutical world, which could be helpful
      to improve their bioavailability and other biochemical aspects like drug delivery
      and gene transfection.

PMID- 25615258
TI  - Urine leak in minimally invasive partial nephrectomy: analysis of risk factors
      and role of intraoperative ureteral catheterization.
AB  - PURPOSE: To investigate risk factors for urine leak in patients undergoing
      minimally invasive partial nephrectomy (MIPN) and to determine the role of
      intraoperative ureteral catheterization in preventing this postoperative
      complication. MATERIALS AND METHODS: MIPN procedures done from September 1999 to
      July 2012 at our Center were reviewed from our IRB-approved database. Patient and
      tumor characteristics, operative techniques and outcomes were analyzed. Patients
      with evidence of urine leak were identified. Outcomes were compared between
      patients with preoperative ureteral catheterization (C-group) and those without
      (NC-group). Univariable and multivariable analyses were performed to identify
      factors predicting postoperative urine leak. RESULTS: A total of 1,019 cases were
      included (452 robotic partial nephrectomy cases and 567 laparoscopic partial
      nephrectomy cases). Five hundred twenty eight patients (51.8%) were in the C
      group, whereas 491 of them (48.2%) in the NC-group. Urine leak occurred in 31(3%)
      cases, 4.6% in the C-group and 1.4% in the NC-group (p<0.001). Tumors in NC-group
      had significantly higher RENAL score, shorter operative and warm ischemic times.
      On multivariable analysis, tumor proximity to collecting system (OR=9.2; p<0.01),
      surgeon's early operative experience (OR=7.8; p<0.01) and preoperative moderate
      to severe CKD (OR=3.1; p<0.01) significantly increased the odds of the occurrence
      of a postoperative urine leak. CONCLUSION: Clinically significant urine leak
      after MIPN in a high volume institution setting is uncommon. This event is more
      likely to occur in cases of renal masses that are close to the collecting system,
      in patients with preoperative CKD and when operating surgeon is still in the
      learning curve for the procedure. Our findings suggest that routine
      intraoperative ureteral catheterization during MIPN does not reduce the
      probability of postoperative urine leak. In addition, it adds to the overall
      operative time.

PMID- 25615260
TI  - Radiofrequency ablation versus resection for the treatment of early stage
      hepatocellular carcinoma: a multicenter Australian study.
AB  - OBJECTIVES: It remains unclear whether radiofrequency ablation (RFA) provides
      comparable outcomes to surgical resection (SR). We, therefore, compared survival
      outcomes of RFA to SR in patients with early stage and very early stage
      hepatocellular carcinoma (HCC). METHODS: A multicenter retrospective analysis was
      performed in patients from five academic hospitals with Barcelona Cancer of the
      Liver Clinic (BCLC) stages 0-A HCC having RFA or SR as primary therapy. RESULTS:
      From 2000-2010, 146 patients who received treatment with RFA (n = 96) or SR (n =
      52) were identified. In BCLC A patients with <=5 cm HCC, there was a trend of
      lower overall survival after RFA compared with SR (3- and 5-year survival: 62%
      and 37% vs. 66% and 62% respectively; p = 0.11). By multivariate analysis, RFA
      was an independent predictor of poor survival (hazard ratio = 2.26; 95%
      confidence interval: 1.02-5.03; p = 0.04). In <=3 cm HCC (n = 109), the 3- and 5
      year survivals in RFA and SR groups were 66% and 39%, and 69% and 59%,
      respectively, with no difference in the median survival (p = 0.41). Local
      recurrence was significantly higher after RFA compared to SR in HCC <=5 cm (p =
      0.006) with a trend of lower recurrence-free survival (p = 0.06) after RFA in HCC
      <=3 cm. There were fewer major complications after RFA (2% vs. 8%). CONCLUSION:
      While SR is superior to RFA for the management of early stage BCLC A disease with
      <=5 cm HCC, both appear effective as first-line treatment options for Western
      patients with small <=3 cm tumors. Although safer than SR, RFA is associated with
      higher rates of tumor recurrence and local disease progression. Further
      prospective randomized controlled trials are warranted to compare these two
      modalities.

PMID- 25615261
TI  - FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation
      properties.
AB  - Three dimensional radiation dosimetry has received growing interest with the
      implementation of highly conformal radiotherapy treatments. The radiotherapy
      community faces new challenges with the commissioning of image guided and image
      gated radiotherapy treatments (IGRT) and deformable image registration software.A
      new three dimensional anthropomorphically shaped flexible dosimeter, further
      called 'FlexyDos3D', has been constructed and a new fast optical scanning method
      has been implemented that enables scanning of irregular shaped dosimeters. The
      FlexyDos3D phantom can be actuated and deformed during the actual treatment.
      FlexyDos3D offers the additional advantage that it is easy to fabricate, is non
      toxic and can be molded in an arbitrary shape with high geometrical precision.The
      dosimeter formulation has been optimized in terms of dose sensitivity. The
      influence of the casting material and oxygen concentration has also been
      investigated. The radiophysical properties of this new dosimeter are discussed
      including stability, spatial integrity, temperature dependence of the dosimeter
      during radiation, readout and storage, dose rate dependence and tissue
      equivalence. 

PMID- 25615262
TI  - Identification of the main retrogradation-related properties of rice starch.
AB  - The retrogradation of rice in shelf life is the biggest barrier to the industrial
      production of traditional foods using rice as material. Many rice breeders have
      tried their best to screen low-retrogradation rice cultivars without a specific
      indicator. To identify the main retrogradation-related properties of rice, the
      starch, amylose, and amylopectin from 16 rice cultivars were extracted from rice
      powder and their physicochemical properties, such as visible absorbance,
      infrared, average molecule weight (amylopectin), chain-length distribution
      (amylopectin), X-ray diffraction, and differential scanning calorimetry, were
      determined. The correlation between starch retrogradation rates and those
      physicochemical properties was investigated. The results show that a significant
      positive correlation (R(2) = 0.85; r = 0.926; p < 0.01) exists only between
      proportions of the chains [degree of polymerization (DP) > 10] in amylopectin and
      the retrogradation rates of different rice starches. The findings in the paper
      offer a shortcut for rice breeders to screen cultivars with a low retrogradation
      rate. Because the genes related to the branching enzyme control the DP of
      amylopectin, they can be exploited as molecular markers to screen low
      retrogradation rice cultivars.

PMID- 25615263
TI  - NMR characterization of PAMAM_G5.NH2 entrapped atomic and molecular assemblies.
AB  - High resolution NMR spectroscopy, NMR diffusiometry, and NMR cryoporometry have
      been used to investigate aqueous solution (D2O) of PAMAM_G5.NH2-(Au)(25-100) and
      PAMAM_G5.NH2-(H2O)1000-(H2O)4000 systems. In the case of dendrimer entrapped gold
      nanoparticles, the detailed analysis of high resolution NMR spectra has shown
      that no precursor complex formation happens under the circumstances applied for
      reduction. Further PGSE results verify that gold nanoparticles of 1.9-2.6 nm size
      are entrapped in the outermost part of the dendrimers and probably more than one
      dendrimer molecule takes part in the stabilization process. This system looks
      like a transition state between dendrimer encapsulated nanoparticles (DENs) and
      dendrimer stabilized nanoparticles (DSNs), and we deal with it in details for
      what this means. NMR cryoporometry experiments were performed to detect the
      encapsulation of water molecules. The results show that, in the swelling
      PAMAM_G5.NH2 dendrimers, by adding water step by step, there are specific
      cavities for water with diameters of 3.6 and 5.2 nm. These cavities have a
      penetrable wall for water molecules and probably exist very close to the terminal
      groups. The permeability of the cavities is increasing with the increase of the
      water content. In dilute solution, the formation of nanoparticles is determined
      by the ratio of the rate of nucleation and aggregation and the latter is affected
      by the PAMAM_G5.NH2.

PMID- 25615264
TI  - Immunophenotyping lymphocyte subsets in canine lymph nodes.

PMID- 25615265
TI  - Long noncoding RNA transcriptome of plants.
AB  - Since their discovery more than two decades ago, animal long noncoding RNAs
      (lncRNAs) have emerged as important regulators of many biological processes.
      Recently, a large number of lncRNAs have also been identified in higher plants,
      and here, we review their identification, classification and known regulatory
      functions in various developmental events and stress responses. Knowledge gained
      from a deeper understanding of this special group of noncoding RNAs may lead to
      biotechnological improvement of crops. Some possible examples in this direction
      are discussed. 

PMID- 25615266
TI  - Novel roles of hydrogen peroxide (H2O2) in regulating pectin synthesis and
      demethylesterification in the cell wall of rice (Oryza sativa) root tips.
AB  - Hydrogen peroxide (H2O2) has been reported to increase lignin formation, enhance
      cell wall rigidification, restrict cell expansion and inhibit root elongation.
      However, our results showed that it not only inhibited rice (Oryza sativa) root
      elongation, but also increased root diameter. No study has reported how and why
      H2O2 increases cell expansion and root diameter. Exogenous H2O2 and its scavenger
      4-hydroxy-Tempo were applied to confirm the roles of H2O2. Immunofluorescence,
      fluorescence probe, ruthenium red staining, histological section and
      spectrophotometry were used to monitor changes in the degree of pectin
      methylesterification, pectin content, pectin methylesterase (PME) activity and
      H2O2 content. Exogenous H2O2 inhibited root elongation, but increased cell
      expansion and root diameter significantly. H2O2 not only increased the region of
      pectin synthesis and pectin content in root tips, but also increased PME activity
      and pectin demethylesterification. The scavenger 4-hydroxy-Tempo reduced root
      H2O2 content and recovered H2O2-induced increases in cell expansion and root
      diameter by inhibiting pectin synthesis, PME activity and pectin
      demethylesterification. H2O2 plays a novel role in the regulation of pectin
      synthesis, PME activity and pectin demethylesterification. H2O2 increases cell
      expansion and root diameter by increasing pectin content and
      demethylesterification.

PMID- 25615267
TI  - Improved design of PPRHs for gene silencing.
AB  - Nowadays, the modulation of gene expression by nucleic acids has become a routine
      tool in biomedical research for target validation and it is also used to develop
      new therapeutic approaches. Recently, we developed the so-called polypurine
      reverse Hoogsteen hairpins (PPRHs) that show high stability and a low immunogenic
      profile and we demonstrated their efficacy both in vitro and in vivo. In this
      work, we explored different characteristics of PPRHs to improve their usage as a
      tool for gene silencing. We studied the role of PPRH length in the range from 20
      to 30 nucleotides. We also proved their higher affinity of binding and efficacy
      on cell viability compared to nonmodified TFOs. To overcome possible off-target
      effects, we tested wild-type PPRHs, which proved to be capable of binding to
      their target sequence with more affinity, displaying a higher stability of
      binding and a higher effect in terms of cell viability. Moreover, we developed a
      brand new molecule called Wedge-PPRH with the ability to lock the ds-DNA into the
      displaced structure and proved its efficacy in prostate and breast cancer cell
      lines. 

PMID- 25615268
TI  - Hepatitis E virus enters liver cells through a dynamin-2, clathrin and membrane
      cholesterol-dependent pathway.
AB  - The hepatitis E virus (HEV) causes large outbreaks and sporadic cases of acute
      viral hepatitis in developing countries. In the developed world, HEV occurrence
      has increased as a result of zoonotic transmission from swine. The cellular
      aspects of HEV infection, especially the determinants of entry, are poorly
      understood. In the absence of a robust in vitro culture system for HEV, it is not
      possible to produce high titre infectious virus that can be labeled for tracking
      its internalization. We have therefore used an Escherichia coli expressed HEV
      like particle (HEV-LP) to study HEV entry. Following internalization, the HEV-LP
      initially trafficks to Rab5-positive compartments en route to acidic lysosomal
      compartments where it is degraded. Using pharmacological inhibitors, dominant
      negative and constitutively active mutants, and siRNA-mediated perturbations, we
      show that HEV entry requires dynamin-2, clathrin, membrane cholesterol and actin,
      but is independent of factors associated with macropinocytosis. The HEV-LP
      results were further validated through infection of liver cells with virus from
      the stool of an infected patient. The comparative analysis also showed
      involvement of the phosphatidylinositol-3-kinase/Akt pathway in an early post
      entry step of viral replication. This report provides a detailed description of
      endocytic processes associated with HEV infection. 

PMID- 25615269
TI  - Illustrations enhance older colorectal cancer patients' website satisfaction and
      recall of online cancer information.
AB  - This study aims to investigate the effects of illustrations in online cancer
      information on older cancer patients' website satisfaction (i.e. satisfaction
      with the attractiveness, comprehensibility and emotional support from the
      website) and recall of information. In an online experiment, 174 younger (<65
      years) and older (>=65 years) colorectal cancer patients were randomly exposed to
      a webpage about transanal endoscopic microsurgery consisting of either text-only
      information, text with two cognitive illustrations or text with two affective
      illustrations. In general, adding cognitive illustrations compared with text-only
      information improved the satisfaction with the attractiveness of the website in
      both younger and older patients. For older patients in particular, cognitive
      illustrations facilitated recall of cancer information: whereas older patients
      recalled less information overall compared with younger patients (39% vs. 50%),
      no statistically significant differences in age on recall were observed when
      cognitive illustrations were added to text. Furthermore, older patients were more
      satisfied with the emotional support from the website than younger patients,
      especially when affective illustrations were present. Our results suggest that
      effective online cancer communication for ageing populations involves considering
      both cognitive and affective illustrations to enhance website satisfaction and
      recall of cancer information. 

PMID- 25615270
TI  - Molecularly engineered quantum dots for visualization of hydrogen sulfide.
AB  - Among various fluorescence nanomaterials, the II-VI semiconductor nanocrystals
      (usually called quantum dots, QDs) should be very promising in sensing
      application because of their high quantum yields, capability for surface property
      manipulation, and unlimited possible chemical reactions. Herein, we present a
      fluorescence probe for hydrogen sulfide, which was prepared by first
      encapsulating inorganic cadmium telluride (CdTe) QDs in silica nanospheres, and
      subsequently engineering the silica surface with functional molecules
      azidocoumarin-4-acetic acid reactive to hydrogen sulfide. The nanohybrid probe
      exhibited two fluorescence bands centered at 452 and 657 nm, respectively. The
      red fluorescence at 657 nm of the nanohybrid probe is stable against H2S, while
      the blue fluorescence is specifically sensitive to H2S. The probe showed a
      distinct fluorescence color evolution from light magenta to blue upon exposure to
      different amounts of H2S, and a detection limit of 7.0 nM was estimated in
      aqueous solution. We further applied the nanohybrid probe for visual detection of
      gaseous H2S with a low concentration of 0.5 ppm using glass indicating spots
      sensors, suggesting its potential application for gaseous H2S sensing. Such an
      efficient on-site visual determination of gaseous hydrogen sulfide (H2S) is
      highly demanded in on-site environmental monitoring and protection. 

PMID- 25615271
TI  - Theoretical studies on polynuclear {Cu(II)5Gd(III)n} clusters (n = 4, 2): towards
      understanding their large magnetocaloric effect.
AB  - Density functional theory (DFT) studies on two polynuclear clusters,
      [Cu(II)5Gd(III)4O2(OMe)4(teaH)4(O2CC(CH3)3)2(NO3)4] (1) and [Cu5Gd2(OH)4(Br)2
      (H2L)2(H3L)2(NO3)2(OH2)4] (2), have been carried out to probe the origin of the
      large magnetocaloric effect (MCE). The magnetic exchange interactions for 1 and 2
      via multiple pathways are estimated using DFT calculations. While the calculated
      exchange parameters deviate from previous experimental estimates obtained by
      fitting the magnetic data, the DFT parameter set is found to offer a striking
      match to the magnetic data for both complexes, highlighting the problem of
      overparameterization. Magnetostructural correlations for {Cu-Gd} pairs have been
      developed where both the Cu-O-Gd angles and Cu-O-Gd-O dihedral angles are found
      to significantly influence the magnitude and sign of the exchange constants. The
      magnitude of the MCE has been examined as a function of the exchange
      interactions, and clues on how the effect can be enhanced are discussed. 

PMID- 25615272
TI  - Sample length affects the reliability of language sample measures in 3-year-olds:
      evidence from parent-elicited conversational samples.
AB  - PURPOSE: The goal of this study was to investigate the extent to which sample
      length affected the reliability of total number of words (TNW), number of
      different words (NDW), and mean length of C-units in morphemes (MLCUm) in parent
      elicited conversational samples for 3-year-olds. METHOD: Participants were sixty
      3-year-olds. A 22-min language sample was collected from each child during free
      play with the parent in the laboratory. Samples of 1, 3, 7, and 10 min were
      extracted from the 22-min samples. TNW, NDW, and MLCUm were computed from each
      shorter sample and the 22-min sample. TNW and NDW were adjusted by number of
      minutes for comparisons. The differences and correlations between each shorter
      sample cut and the 22-min sample on MLCUm and adjusted TNW and NDW were computed.
      RESULTS: The shorter samples and the 22-min samples significantly differed in
      adjusted TNW and NDW, but not in MLCUm. TNW reached an acceptable reliability
      level (i.e., r = .90) in 7-min samples. NDW and MLCUm approached the acceptable
      reliability level (rs = .88) in 7-min samples and reached it in 10-min samples.
      CONCLUSION: For conversational language samples with similar collection
      procedures, samples of 7 to 10 min are desirable for calculating TNW, NDW, and
      MLCUm in 3-year-olds.

PMID- 25615273
TI  - Ocular hypertension results in retinotopic alterations in the visual cortex of
      adult mice.
AB  - PURPOSE: Glaucoma is a group of optic neuropathies characterized by the loss of
      retinal ganglion cells (RGCs). Since ocular hypertension (OHT) is a main risk
      factor, current therapies are predominantly based on lowering eye pressure.
      However, a subset of treated patients continues to lose vision. More research
      into pathological mechanisms underlying glaucoma is therefore warranted in order
      to develop novel therapeutic strategies. In this study we investigated the impact
      of OHT from eye to brain in mice. METHODS: Monocular hypertension (mOHT) was
      induced in CD-1 mice by laser photocoagulation (LP) of the perilimbal and
      episcleral veins. The impact on the retina and its main direct target area, the
      superficial superior colliculus (sSC), was examined via immunostainings for
      Brn3a, VGluT2 and GFAP. Alterations in neuronal activity in V1 and extrastriate
      areas V2L and V2M were assessed using in situ hybridization for the activity
      reporter gene zif268. RESULTS: Transient mOHT resulted in diffuse and sectorial
      RGC degeneration. In the sSC contralateral to the OHT eye, a decrease in VGluT2
      immunopositive synaptic connections was detected one week post LP, which appeared
      to be retinotopically linked to the sectorial RGC degeneration patterns. In
      parallel, hypoactivity was discerned in contralateral retinotopic projection
      zones in V1 and V2. Despite complete cortical reactivation 4 weeks post LP, in
      the sSC no evidence for recovery of RGC synapse density was found and also the
      concomitant inflammation was not completely resolved. Nevertheless, sSC neurons
      appeared healthy upon histological inspection and subsequent analysis of cell
      density revealed no differences between the ipsi- and contralateral sSC.
      CONCLUSION: In addition to RGC death, OHT induces loss of synaptic connections
      and neuronal activity in the visual pathway and is accompanied by an extensive
      immune response. Our findings stress the importance of looking beyond the eye and
      including the whole visual system in glaucoma research.

PMID- 25615274
TI  - Different Ways to On-Line Hyphenate Centrifugal Partition Chromatography and Mass
      Spectrometry: Application to Prenylated Xanthones from Garcinia mangostana.
AB  - Centrifugal partition chromatography is a liquid-liquid separation method well
      adapted for the fractionation or purification of natural compounds from plant
      extracts. However, following the preparative isolation, the fractions collected
      must be analysed by high-performance thin-layer chromatography or high
      performance liquid chromatography to evaluate their composition and/or their
      purity. These additional steps are time-consuming and increase the risk of
      compound degradation. In order to get an instantaneous analysis of fraction
      content with structural information on the phytochemicals eluted, it is possible
      to hyphenate on-line centrifugal partition chromatography with mass spectrometry.
      Depending on the complexity of the extract, two different kinds of centrifugal
      partition chromatography-mass spectrometry coupling can be performed: centrifugal
      partition chromatography-mass spectrometry or centrifugal partition
      chromatography-high-performance liquid chromatography-mass spectrometry coupling.
      In the first case, one part of the centrifugal partition chromatography effluent
      is directly introduced in the mass spectrometry ionisation source to identify the
      eluted compounds, while in the second case, it is directed to a high-performance
      liquid chromatography-mass spectrometry system where compounds are first
      separated thanks to high-performance liquid chromatography and then identified
      using mass spectrometry. 

PMID- 25615275
TI  - Prediction of Anti-inflammatory Plants and Discovery of Their Biomarkers by
      Machine Learning Algorithms and Metabolomic Studies.
AB  - Nonsteroidal anti-inflammatory drugs are the most used anti-inflammatory
      medicines in the world. Side effects still occur, however, and some inflammatory
      pathologies lack efficient treatment. Cyclooxygenase and lipoxygenase pathways
      are of utmost importance in inflammatory processes; therefore, novel inhibitors
      are currently needed for both of them. Dual inhibitors of cyclooxygenase-1 and 5
      lipoxygenase are anti-inflammatory drugs with high efficacy and low side effects.
      In this work, 57 leaf extracts (EtOH-H2O 7 : 3, v/v) from Asteraceae species with
      in vitro dual inhibition of cyclooxygenase-1 and 5-lipoxygenase were analyzed by
      high-performance liquid chromatography-high-resolution-ORBITRAP-mass spectrometry
      analysis and subjected to in silico studies using machine learning algorithms.
      The data from all samples were processed by employing differential expression
      analysis software coupled to the Dictionary of Natural Products for dereplication
      studies. The 6052 chromatographic peaks (ESI positive and negative modes) of the
      extracts were selected by a genetic algorithm according to their respective anti
      inflammatory properties; after this procedure, 1241 of them remained. A study
      using a decision tree classifier was carried out, and 11 compounds were
      determined to be biomarkers due to their anti-inflammatory potential. Finally, a
      model to predict new biologically active extracts from Asteraceae species using
      liquid chromatography-mass spectrometry information with no prior knowledge of
      their biological data was built using a multilayer perceptron (artificial neural
      networks) with the back-propagation algorithm using the biomarker data. As a
      result, a new and robust artificial neural network model for predicting the anti
      inflammatory activity of natural compounds was obtained, resulting in a high
      percentage of correct predictions (81 %), high precision (100 %) for dual
      inhibition, and low error values (mean absolute error = 0.3), as also shown in
      the validation test. Thus, the biomarkers of the Asteraceae extracts were
      statistically correlated with their anti-inflammatory activities and can
      therefore be useful to predict new anti-inflammatory extracts and their anti
      inflammatory compounds using only liquid chromatography-mass spectrometry data.

PMID- 25615276
TI  - Effects of diene valepotriates from Valeriana glechomifolia on Na+/K+-ATPase
      activity in the cortex and hippocampus of mice.
AB  - Diene valepotriates obtained from Valeriana glechomifolia present antidepressant
      like activity, mediated by dopaminergic and noradrenergic neurotransmissions.
      Also, previous studies have shown inhibitory activity of diene valepotriates
      towards Na(+)/K(+)-ATPase from the rat brain in vitro. Nevertheless, in vivo
      studies regarding the action of diene valepotriates on this enzyme are still
      lacking. Considering that Na(+)/K(+)-ATPase cerebral activity is involved in
      depressive disorders, the aim of this study was to investigate the effects of
      acute (5 mg/kg, p. o.) and repeated (5 mg/kg, p. o., once a day for three days)
      diene valepotriate administration on Na(+)/K(+)-ATPase activity in the cortex and
      hippocampus of mice submitted or not submitted to the forced swimming test. In
      addition, the protein expression of Na(+)/K(+)-ATPase alpha1, alpha2, and alpha3
      isoforms in the cortex of mice repeatedly treated with diene valepotriates (and
      submitted or not submitted to the forced swimming test) was investigated. Diene
      valepotriates significantly decreased mice immobility time in the forced swimming
      test when compared to the control group. Only the animals repeatedly treated with
      diene valepotriates presented increased Na(+)/K(+)-ATPase activity in the
      cerebral cortex, and the exposure to the forced swimming test counteracted the
      effects of the diene valepotriates. No alterations in the hippocampal Na(+)/K(+)
      ATPase activity were observed. Repeated diene valepotriate administration
      increased the cortical content of the alpha2 isoform, but the alpha3 isoform
      protein expression was augmented only in mice repeatedly treated with diene
      valepotriates and forced to swim. Mice treated with the vehicle and submitted to
      the forced swimming test also presented an increase in the content of the alpha2
      isoform, but no alterations in Na(+)/K(+)-ATPase activity. These results suggest
      that cortical Na(+)/K(+)-ATPase may represent a molecular target of the diene
      valepotriates in vivo and long-term regulatory mechanisms are involved in this
      effect. Also, the forced swimming test per se influences the protein expression
      of Na(+)/K(+)-ATPase isoforms and counteracts the effects of the diene
      valepotriates on cortical Na(+)/K(+)-ATPase. 

PMID- 25615277
TI  - Subtle skin involvement in nodal gammadelta peripheral T-cell lymphoma.

PMID- 25615278
TI  - Developing a mobile electronic D2B checklist for treatment of ST elevation
      myocardial infarction patients who need a primary coronary intervention.
AB  - ST elevation myocardial infarction (STEMI), one main type of acute myocardial
      infarction with high mortality, requires percutaneous coronary intervention (PCI)
      with balloon inflation. Current guidelines recommend a door-to-balloon (D2B)
      interval (i.e., starts with the patient's arrival in the emergency department and
      ends when PCI with a catheter guidewire and balloon inflation crosses the culprit
      lesion) of no more than 90 min. However, promptly implementing PCI requires
      coordinating various medical teams. Checklists can be used to ensure consistency
      and operating sequences when executing complex tasks in a clinical routine.
      Developing an effective D2B checklist would enhance the care of STEMI patients
      who need PCI. Mobile information and communication technologies have the
      potential to greatly improve communication, facilitate access to information, and
      eliminate duplicated documentation without the limitations of space and time. In
      a research project by the Chi Mei Medical Center, "Developing a Mobile Electronic
      D2B Checklist for Managing the Treatment of STEMI Patients Who Need Primary
      Coronary Intervention," a prototype version of a mobile checklist was developed.
      This study describes the research project and the four phases of the system
      development life cycle, comprising system planning and selection, analysis,
      design, and implementation and operation. Face-to-face interviews with 16
      potential users were conducted and revealed highly positive user perception and
      use intention toward the prototype. Discussion and directions for future research
      are also presented.

PMID- 25615279
TI  - Minimal residual disease detection with tumor-specific CD160 correlates with
      event-free survival in chronic lymphocytic leukemia.
AB  - In chronic lymphocytic leukemia (CLL), the detection of minimal residual disease
      (MRD) correlates with outcome in the trial setting. However, MRD assessment does
      not guide routine clinical management and its assessment remains complex. We
      incorporated detection of the B cell, tumor-specific antigen CD160 to develop a
      single-tube, flow cytometry assay (CD160FCA) for CLL MRD to a threshold of 10(-4)
      to 10(-5). One hundred and eighty-seven patients treated for CLL were enrolled.
      Utilizing the CD160FCA methodology, there was a high level of comparison between
      blood and bone marrow (R=0.87, P<0.001). In a validation cohort, CD160FCA and the
      international standardised approach of the European Research Initiative on CLL
      group demonstrated high concordance (R=0.91, P<0.01). Patients in complete
      remission (CR) and CD160FCA negative had longer event-free survival (EFS) (63 vs
      16 months, P<0.01) and prolonged time to next treatment (60 vs 15 months,
      P<0.001) vs MRD positive patients; with a median time to MRD positivity of 36
      months. In multivariate analysis, CD160FCA MRD detection was independently
      predictive of EFS in patients in CR and even predicted EFS in the good-risk
      cytogenetic subgroup. CD160FCA offers a simple assay for MRD detection in CLL and
      gives prognostic information across different CLL risk groups. 

PMID- 25615281
TI  - Novel recurrent mutations in ethanolamine kinase 1 (ETNK1) gene in systemic
      mastocytosis with eosinophilia and chronic myelomonocytic leukemia.
AB  - Although KITD816V occurs universally in adult systemic mastocytosis (SM), the
      clinical heterogeneity of SM suggests presence of additional phenotype-patterning
      mutations. Because up to 25% of SM patients have KITD816V-positive eosinophilia,
      we undertook whole-exome sequencing in a patient with aggressive SM with
      eosinophilia to identify novel genetic alterations. We conducted sequencing of
      purified eosinophils (clone/tumor sample), with T-lymphocytes as the matched
      control/non-tumor sample. In addition to KITD816V, we identified a somatic
      missense mutation in ethanolamine kinase 1 (ETNK1N244S) that was not present in
      50 healthy controls. Targeted resequencing of 290 patients showed ETNK1 mutations
      to be distributed as follows: (i) SM (n=82; 6% mutated); (ii) chronic
      myelomonocytic leukemia (CMML; n=29; 14% mutated); (iii) idiopathic
      hypereosinophilia (n=137; <1% mutated); (iv) primary myelofibrosis (n=32; 0%
      mutated); and (v) others (n=10; 0% mutated). Of the 82 SM cases, 25 had
      significant eosinophilia; of these 20% carried ETNK1 mutations. The ten mutations
      (N244S=6, N244T=1, N244K=1, G245A=2) targeted two contiguous amino acids in the
      ETNK1 kinase domain, and are predicted to be functionally disruptive. In summary,
      we identified novel somatic missense ETNK1 mutations that were most frequent in
      SM with eosinophilia and CMML; this suggests a potential pathogenetic role for
      dysregulated cytidine diphosphate-ethanolamine pathway metabolites in these
      diseases. 

PMID- 25615280
TI  - Autophagy collaborates with ubiquitination to downregulate oncoprotein E2A/Pbx1
      in B-cell acute lymphoblastic leukemia.
AB  - B-cell acute lymphoblastic leukemia (B-ALL) accounts for the most cancer
      incidences in children. We present here that autophagy is downregulated in
      pediatric B-ALL, suggesting a possible link between autophagy failure and
      pediatric B-ALL leukemogenesis. With a pediatric t(1;19) B-ALL xenograft mouse
      model, we show here that activation of autophagy by preventive administration of
      rapamycin improved the survival of leukemia animals by partial restoration of
      hematopoietic stem/progenitor cells, whereas treatment of the animals with
      rapamycin caused leukemia bone marrow cell-cycle arrest. Activation of autophagy
      in vitro or in vivo by rapamycin or starvation downregulated oncogenic fusion
      protein E2A/Pbx1. Furthermore, E2A/Pbx1 was found to be colocalized with
      autophagy marker LC3 in autolysosomes and with ubiquitin in response to autophagy
      stimuli, whereas autophagy or ubiquitination inhibitor blocked these
      colocalizations. Together, our data suggest a collaborative action between
      autophagy and ubiquitination in the degradation of E2A/Pbx1, thereby revealing a
      novel strategy for targeted preventive or treatment therapy on the pediatric ALL.

PMID- 25615282
TI  - Local delivery of paclitaxel in the treatment of peripheral arterial disease.
AB  - BACKGROUND: Despite advancements from balloon angioplasty to drug-eluting stents,
      primary patency rates after endovascular revascularization of peripheral artery
      disease have remained inferior compared to surgery. Endovascular
      revascularization has been limited by restenosis and mechanical stent failure.
      Thus, there is increased research into other nonstent-based local drug delivery
      modalities, which can provide an active drug to inhibit restenosis focally and
      avoid the risk of systemic adverse effects. METHODS: This review will summarize
      the unique properties of paclitaxel and studies on paclitaxel local delivery for
      the treatment of peripheral artery disease. A MEDLINE search for relevant peer
      reviewed scientific literature published in English was conducted. Search terms
      included but were not limited to paclitaxel pharmacodynamics, paclitaxel local
      drug delivery, and drug eluting balloons, with a focus on the use of paclitaxel
      in the context of coronary and peripheral vascular disease. RESULTS: The primary
      search produced 182 results of which 51 papers were relevant. Of the 51 relevant
      papers, 27 were original research papers and 24 were either review papers,
      commentary or opinion papers. CONCLUSIONS: Paclitaxel has several chemical
      properties, which make it ideal for local drug delivery including its
      hydrophobicity, ability to concentrate into the arterial intima layer and
      prolonged effect on cells even after brief exposure periods. Local delivery of
      paclitaxel via injection catheters, balloon catheters and coated balloons has
      shown encouraging results in terms of efficacy and safety in small-scale animal
      and clinical studies. Additional preclinical and clinical studies are needed to
      determine the long-term efficacy and safety of these treatments in humans.

PMID- 25615283
TI  - Experimental phase diagram of negatively supercoiled DNA measured by magnetic
      tweezers and fluorescence.
AB  - The most common form of DNA is the well-known B-structure of double-helix DNA.
      Many processes in the cell, however, exert force and torque, inducing structural
      changes to the DNA that are vital to biological function. Virtually all DNA in
      cells is in a state of negative supercoiling, with a DNA structure that is
      complex. Using magnetic tweezers combined with fluorescence imaging, we here
      study DNA structure as a function of negative supercoiling at the single-molecule
      level. We classify DNA phases based on DNA length as a function of supercoiling,
      down to a very high negative supercoiling density sigma of -2.5, and forces up to
      4.5 pN. We characterize plectonemes using fluorescence imaging. DNA bubbles are
      visualized by the binding of fluorescently labelled RPA, a eukaryotic single
      strand-binding protein. The presence of Z-DNA, a left-handed form of DNA, is
      probed by the binding of Zalpha77, the minimal binding domain of a Z-DNA-binding
      protein. Without supercoiling, DNA is in the relaxed B-form. Upon going toward
      negative supercoiling, plectonemic B-DNA is being formed below 0.6 pN. At higher
      forces and supercoiling densities down to about -1.9, a mixed state occurs with
      plectonemes, multiple bubbles and left-handed L-DNA. Around sigma = -1.9, a
      buckling transition occurs after which the DNA end-to-end length linearly
      decreases when applying more negative turns, into a state that we interpret as
      plectonemic L-DNA. By measuring DNA length, Zalpha77 binding, plectoneme and
      ssDNA visualisation, we thus have mapped the co-existence of many DNA structures
      and experimentally determined the DNA phase diagram at (extreme) negative
      supercoiling. 

PMID- 25615284
TI  - Acoustic radiation force impulse elastography of prostate and testes of  healthy
      dogs: preliminary results.
AB  - OBJECTIVES: To describe the use of acoustic radiation force impulse elastography
      to evaluate the prostate and testes in healthy dogs and establish reference
      values for these organs. METHODS: Thirty dogs were divided into three groups
      according to their age: juvenile, adult and senior. Echotexture, size, contours
      and margins of prostate and testes were assessed via ultrasound. The presence of
      deformities and tissue stiffness (greyscale and homogeneous or heterogeneous)
      were evaluated by qualitative acoustic radiation force impulse. The shear
      velocity was evaluated quantitatively. RESULTS: The B mode findings were normal.
      The qualitative elastography demonstrated that the testes and prostate tissues
      were hard, homogeneous and not pliable. The shear velocity values were: left
      testes - juveniles: 1.28 m/s, adults: 1.23 m/s and seniors: 1.23 m/s; right
      testes - juveniles: 1.28 m/s, adults: 1.28 m/s and seniors: 1.28 m/s; left
      prostatic lobe - juveniles: 1.74 m/s, adults: 2.03 m/s and seniors: 1.82 m/s;
      right prostatic lobe - juvenile: 1.62 m/s, adults: 1.87 m/s and seniors: 1.90 m/s
      with no significant differences between groups. CLINICAL SIGNIFICANCE: Acoustic
      radiation force impulse elastography of the testes and prostate in dogs was
      easily implemented. This study provides baseline data for these organs.

PMID- 25615285
TI  - Regulation of Inflammatory Cytokine Production by MKP-5 in Macrophages.
AB  - Mitogen-activated protein kinases (MAPKs) include p38 MAPKs, c-Jun N-terminal
      kinases (JNKs) and Extracellular signal-regulated kinases (ERKs), and they
      regulate many cell processes, such as cell division, differentiation and release
      of inflammatory mediators. MAPK activity is controlled by mitogen-activated
      protein kinase phosphatases (MKPs), a phosphatase family with 11 members. MKP-1
      is the most studied member of MKP family, and it is one of the anti-inflammatory
      factors induced by glucocorticoids. Less is known about the other MAPK
      phosphatases although they hold a promise as anti-inflammatory drug targets. In
      this study, we investigated the effect of MKP-5 on MAPK phosphorylation and
      cytokine production in J774 mouse macrophages. We used MKP-5 siRNA and an MKP-5
      inhibitor (AS077234-4) to modulate MKP-5 function. We found that MKP-5 controlled
      p38 MAPK phosphorylation, but not that of JNK or ERK. In addition, the production
      of IL-6 and TNF was suppressed by MKP-5 in macrophages. Our results introduce a
      novel concept that compounds able to enhance MKP-5 expression and/or activity
      hold anti-inflammatory potential, because MKP-5 down-regulates the release of
      inflammatory mediators by controlling p38 MAPK activity. 

PMID- 25615286
TI  - Generation-dependent templated self-assembly of biohybrid protein nanoparticles
      around photosensitizer dendrimers.
AB  - In this article, we show the great potential of dendrimers for driving the self
      assembly of biohybrid protein nanoparticles. Dendrimers are periodically branched
      macromolecules with a perfectly defined and monodisperse structure. Moreover,
      they allow the possibility to incorporate functional units at predetermined
      sites, either at their core, branches, or surface. On these bases, we have
      designed and synthesized negatively charged phthalocyanine (Pc) dendrimers that
      behave as photosensitizers for the activation of molecular oxygen into singlet
      oxygen, one of the main reactive species in photodynamic therapy (PDT). The
      number of surface negative charges depends on dendrimer generation, whereas Pc
      aggregation can be tuned through the appropriate choice of the Pc metal center
      and its availability for axial substitution. Remarkably, both parameters
      determine the outcome and efficiency of the templated self-assembly process by
      which a virus protein forms 18 nm virus-like particles around these dendritic
      chromophores. Protein-dendrimer biohybrid nanoparticles of potential interest for
      therapeutic delivery purposes are obtained in this way. Biohybrid assemblies of
      this kind will have a central role in future nanomedical and nanotechnology
      applications. 

PMID- 25615288
TI  - Stronger uncertainty relations for all incompatible observables.
AB  - The Heisenberg-Robertson uncertainty relation expresses a limitation in the
      possible preparations of the system by giving a lower bound to the product of the
      variances of two observables in terms of their commutator. Notably, it does not
      capture the concept of incompatible observables because it can be trivial; i.e.,
      the lower bound can be null even for two noncompatible observables. Here we give
      two stronger uncertainty relations, relating to the sum of variances, whose lower
      bound is guaranteed to be nontrivial whenever the two observables are
      incompatible on the state of the system. 

PMID- 25615287
TI  - Salt sensitivity in chickpea (Cicer arietinum L.): ions in reproductive tissues
      and yield components in contrasting genotypes.
AB  - The reproductive phase in chickpea (Cicer arietinum L.) is affected by salinity,
      but little is known about the underlying cause. We investigated whether high
      concentrations of Na(+) and Cl(-) in the reproductive structures influence
      reproductive processes. Chickpea genotypes contrasting in tolerance were
      subjected to 0, 35 or 50 mm NaCl applied to soil in pots. Flower production and
      abortion, pod number, percentage of empty pods, seed number and size were
      evaluated. The concentrations of Na(+) , K(+) and Cl(-) were measured in various
      plant tissues and, using X-ray microanalysis, in specific cells of developing
      reproductive structures. Genotypic variation in reproductive success measured as
      seed yield in saline conditions was associated with better maintenance of flower
      production and higher numbers of filled pods (and thus seed number), whereas seed
      size decreased in all genotypes. Despite the variation in reproductive success,
      the accumulation of Na(+) and Cl(-) in the early reproductive tissues of
      developing pods did not differ between a tolerant (Genesis836) and a sensitive
      (Rupali) genotype. Similarly, salinity tolerance was not associated with the
      accumulation of salt ions in leaves at the time of reproduction or in seeds at
      maturity. 

PMID- 25615289
TI  - Probabilistic metrology attains macroscopic cloning of quantum clocks.
AB  - It has recently been shown that probabilistic protocols based on postselection
      boost the performances of the replication of quantum clocks and phase estimation.
      Here we demonstrate that the improvements in these two tasks have to match
      exactly in the macroscopic limit where the number of clones grows to infinity,
      preserving the equivalence between asymptotic cloning and state estimation for
      arbitrary values of the success probability. Remarkably, the cloning fidelity
      depends critically on the number of rationally independent eigenvalues of the
      clock Hamiltonian. We also prove that probabilistic metrology can simulate
      cloning in the macroscopic limit for arbitrary sets of states when the
      performance of the simulation is measured by testing small groups of clones. 

PMID- 25615290
TI  - Identifying a bath-induced bose liquid in interacting spin-boson models.
AB  - We study the ground state phase diagram of a one-dimensional hard-core bosonic
      model with nearest-neighbor interactions (XXZ model) where every site is coupled
      Ohmically to an independent but identical reservoir, hereby generalizing spin
      boson models to interacting spin-boson systems. We show that a bath-induced Bose
      liquid phase can occur in the ground state phase diagram away from half filling.
      This phase is compressible, gapless, and conducting but not superfluid. At half
      filling, only a Luttinger liquid and a charge density wave are found. The phase
      transition between them is of Kosterlitz-Thouless type where the Luttinger
      parameter takes a nonuniversal value. The applied quantum Monte Carlo method can
      be used for all open bosonic and unfrustrated spin systems, regardless of their
      dimension, filling factor, and spectrum of the dissipation as long as the quantum
      system couples to the bath via the density operators. 

PMID- 25615291
TI  - Reconstructing quantum states from local data.
AB  - We consider the problem of reconstructing global quantum states from local data.
      Because the reconstruction problem has many solutions in general, we consider the
      reconstructed state of maximum global entropy consistent with the local data. We
      show that unique ground states of local Hamiltonians are exactly reconstructed as
      the maximal entropy state. More generally, we show that if the state in question
      is a ground state of a local Hamiltonian with a degenerate space of locally
      indistinguishable ground states, then the maximal entropy state is close to the
      ground state projector. We also show that local reconstruction is possible for
      thermal states of local Hamiltonians. Finally, we discuss a procedure to certify
      that the reconstructed state is close to the true global state. We call the
      entropy of our reconstructed maximum entropy state the "reconstruction entropy,"
      and we discuss its relation to emergent geometry in the context of holographic
      duality. 

PMID- 25615292
TI  - Structural quantification of entanglement.
AB  - We introduce an approach which allows a full structural and quantitative analysis
      of multipartite entanglement. The sets of states with different structures are
      convex and nested. Hence, they can be distinguished from each other using
      appropriate measurable witnesses. We derive equations for the construction of
      optimal witnesses and discuss general properties arising from our approach. As an
      example, we formulate witnesses for a 4-cluster state and perform a full
      quantitative analysis of the entanglement structure in the presence of noise and
      losses. The strength of the method in multimode continuous variable systems is
      also demonstrated for a dephased Greenberger-Horne-Zeilinger-type state. 

PMID- 25615293
TI  - Error distributions on large entangled states with non-Markovian dynamics.
AB  - We investigate the distribution of errors on a computationally useful entangled
      state generated via the repeated emission from an emitter undergoing strongly non
      Markovian evolution. For emitter-environment coupling of pure-dephasing form, we
      show that the probability that a particular patten of errors occurs has a bound
      of Markovian form, and thus, accuracy threshold theorems based on Markovian
      models should be just as effective. Beyond the pure-dephasing assumption, though
      complicated error structures can arise, they can still be qualitatively bounded
      by a Markovian error model. 

PMID- 25615294
TI  - Quantum error suppression with commuting Hamiltonians: two local is too local.
AB  - We consider error suppression schemes in which quantum information is encoded
      into the ground subspace of a Hamiltonian comprising a sum of commuting terms.
      Since such Hamiltonians are gapped, they are considered natural candidates for
      protection of quantum information and topological or adiabatic quantum
      computation. However, we prove that they cannot be used to this end in the two
      local case. By making the favorable assumption that the gap is infinite, we show
      that single-site perturbations can generate a degeneracy splitting in the ground
      subspace of this type of Hamiltonian which is of the same order as the magnitude
      of the perturbation, and is independent of the number of interacting sites and
      their Hilbert space dimensions, just as in the absence of the protecting
      Hamiltonian. This splitting results in decoherence of the ground subspace, and we
      demonstrate that for natural noise models the coherence time is proportional to
      the inverse of the degeneracy splitting. Our proof involves a new version of the
      no-hiding theorem which shows that quantum information cannot be approximately
      hidden in the correlations between two quantum systems. The main reason that two
      local commuting Hamiltonians cannot be used for quantum error suppression is that
      their ground subspaces have only short-range (two-body) entanglement. 

PMID- 25615295
TI  - Irreversible work and inner friction in quantum thermodynamic processes.
AB  - We discuss the thermodynamics of closed quantum systems driven out of equilibrium
      by a change in a control parameter and undergoing a unitary process. We compare
      the work actually done on the system with the one that would be performed along
      ideal adiabatic and isothermal transformations. The comparison with the latter
      leads to the introduction of irreversible work, while that with the former leads
      to the introduction of inner friction. We show that these two quantities can be
      treated on an equal footing, as both can be linked with the heat exchanged in
      thermalization processes and both can be expressed as relative entropies.
      Furthermore, we show that a specific fluctuation relation for the entropy
      production associated with the inner friction exists, which allows the inner
      friction to be written in terms of its cumulants. 

PMID- 25615296
TI  - Atomic clock with 1*10(-18) room-temperature blackbody Stark uncertainty.
AB  - The Stark shift due to blackbody radiation (BBR) is the key factor limiting the
      performance of many atomic frequency standards, with the BBR environment inside
      the clock apparatus being difficult to characterize at a high level of precision.
      Here we demonstrate an in-vacuum radiation shield that furnishes a uniform, well
      characterized BBR environment for the atoms in an ytterbium optical lattice
      clock. Operated at room temperature, this shield enables specification of the BBR
      environment to a corresponding fractional clock uncertainty contribution of
      5.5*10(-19). Combined with uncertainty in the atomic response, the total
      uncertainty of the BBR Stark shift is now 1*10(-18). Further operation of the
      shield at elevated temperatures enables a direct measure of the BBR shift
      temperature dependence and demonstrates consistency between our evaluated BBR
      environment and the expected atomic response.

PMID- 25615297
TI  - Trumpet slices in Kerr spacetimes.
AB  - We introduce a new time-independent family of analytical coordinate systems for
      the Kerr spacetime representing rotating black holes. We also propose a (2+1)+1
      formalism for the characterization of trumpet geometries. Applying this formalism
      to our new family of coordinate systems we identify, for the first time,
      analytical and stationary trumpet slices for general rotating black holes, even
      for charged black holes in the presence of a cosmological constant. We present
      results for metric functions in this slicing and analyze the geometry of the
      rotating trumpet surface. 

PMID- 25615298
TI  - Revised upper limit to energy extraction from a Kerr black hole.
AB  - We present a new upper limit on the energy that may be extracted from a Kerr
      black hole by means of particle collisions in the ergosphere (i.e., the
      "collisional Penrose process"). Earlier work on this subject has focused largely
      on particles with critical values of angular momentum falling into an extremal
      Kerr black hole from infinity and colliding just outside the horizon. While these
      collisions are able to reach arbitrarily high center-of-mass energies, it is very
      difficult for the reaction products to escape back to infinity, effectively
      limiting the peak efficiency of such a process to roughly 130%. When we allow one
      of the initial particles to have impact parameter b>2M, and thus not get captured
      by the horizon, it is able to collide along outgoing trajectories, greatly
      increasing the chance that the products can escape. For equal-mass particles
      annihilating to photons, we find a greatly increased peak energy of Eout~6*Ein.
      For Compton scattering, the efficiency can go even higher, with Eout~14*Ein, and
      for repeated scattering events, photons can both be produced and escape to
      infinity with Planck-scale energies.

PMID- 25615299
TI  - Taming the nonlinearity of the Einstein equation.
AB  - Many of the technical complications associated with the general theory of
      relativity ultimately stem from the nonlinearity of Einstein's equation. It is
      shown here that an appropriate choice of dynamical variables may be used to
      eliminate all such nonlinearities beyond a particular order: Both Landau-Lifshitz
      and tetrad formulations of Einstein's equation are obtained that involve only
      finite products of the unknowns and their derivatives. Considerable additional
      simplifications arise in physically interesting cases where metrics become
      approximately Kerr or, e.g., plane waves, suggesting that the variables described
      here can be used to efficiently reformulate perturbation theory in a variety of
      contexts. In all cases, these variables are shown to have simple geometrical
      interpretations that directly relate the local causal structure associated with
      the metric of interest to the causal structure associated with a prescribed
      background. A new method to search for exact solutions is outlined as well. 

PMID- 25615300
TI  - Hierarchical axion inflation.
AB  - We propose a new field theory mechanism for generating an effective trans
      Planckian decay constant from sub-Planckian ones. Using the minimal two axions
      and a hierarchy between two axion decay constants is sufficient for realizing
      inflation through nonperturbative effects only and with minimal tuning. The
      inflationary motion is kept entirely within a sub-Planckian domain. We outline
      possible strategies of embedding the model in a string theory setup. 

PMID- 25615301
TI  - Understanding the core-halo relation of quantum wave dark matter from 3D
      simulations.
AB  - We examine the nonlinear structure of gravitationally collapsed objects that form
      in our simulations of wavelike cold dark matter, described by the Schrodinger
      Poisson (SP) equation with a particle mass ~10(-22)  eV. A distinct
      gravitationally self-bound solitonic core is found at the center of every halo,
      with a profile quite different from cores modeled in the warm or self-interacting
      dark matter scenarios. Furthermore, we show that each solitonic core is
      surrounded by an extended halo composed of large fluctuating dark matter granules
      which modulate the halo density on a scale comparable to the diameter of the
      solitonic core. The scaling symmetry of the SP equation and the uncertainty
      principle tightly relate the core mass to the halo specific energy, which, in the
      context of cosmological structure formation, leads to a simple scaling between
      core mass (Mc) and halo mass (Mh), Mc?a(-1/2)Mh(1/3), where a is the cosmic scale
      factor. We verify this scaling relation by (i) examining the internal structure
      of a statistical sample of virialized halos that form in our 3D cosmological
      simulations and by (ii) merging multiple solitons to create individual virialized
      objects. Sufficient simulation resolution is achieved by adaptive mesh refinement
      and graphic processing units acceleration. From this scaling relation, present
      dwarf satellite galaxies are predicted to have kiloparsec-sized cores and a
      minimum mass of ~10(8)M?, capable of solving the small-scale controversies in the
      cold dark matter model. Moreover, galaxies of 2*10(12)M? at z=8 should have
      massive solitonic cores of ~2*10(9)M? within ~60  pc. Such cores can provide a
      favorable local environment for funneling the gas that leads to the prompt
      formation of early stellar spheroids and quasars.

PMID- 25615302
TI  - Coupling hydrodynamics to nonequilibrium degrees of freedom in strongly
      interacting quark-gluon plasma.
AB  - Relativistic hydrodynamics simulations of quark-gluon plasma play a pivotal role
      in our understanding of heavy ion collisions at RHIC and LHC. They are based on a
      phenomenological description due to Muller, Israel, Stewart (MIS) and others,
      which incorporates viscous effects and ensures a well-posed initial value
      problem. Focusing on the case of conformal plasma we propose a generalization
      which includes, in addition, the dynamics of the least damped far-from
      equilibrium degree of freedom found in strongly coupled plasmas through the
      AdS/CFT correspondence. We formulate new evolution equations for general flows
      and then test them in the case of N=4 super Yang-Mills plasma by comparing their
      solutions alongside solutions of MIS theory with numerical computations of
      isotropization and boost-invariant flow based on holography. In these tests the
      new equations reproduce the results of MIS theory when initialized close to the
      hydrodynamic stage of evolution, but give a more accurate description of the
      dynamics when initial conditions are set in the preequilibrium regime. 

PMID- 25615303
TI  - Entanglement entropy flow and the Ward identity.
AB  - We derive differential equations for the flow of entanglement entropy as a
      function of the metric and the couplings of the theory. The variation of the
      universal part of entanglement entropy under a local Weyl transformation is
      related to the variation under a local change in the couplings. We show that this
      relation is, in fact, equivalent to the trace Ward identity. As a concrete
      application of our formalism, we express the entanglement entropy for massive
      free fields as a two-point function of the energy-momentum tensor. 

PMID- 25615304
TI  - Singularity structure of maximally supersymmetric scattering amplitudes.
AB  - We present evidence that loop amplitudes in maximally supersymmetric (N=4) Yang
      Mills theory (SYM) beyond the planar limit share some of the remarkable
      structures of the planar theory. In particular, we show that through two loops,
      the four-particle amplitude in full N=4 SYM has only logarithmic singularities
      and is free of any poles at infinity--properties closely related to uniform
      transcendentality and the UV finiteness of the theory. We also briefly comment on
      implications for maximal (N=8) supergravity theory (SUGRA).

PMID- 25615305
TI  - Collinear limit of scattering amplitudes at strong coupling.
AB  - In this Letter, we consider the collinear limit of gluon scattering amplitudes in
      planar N=4 super-Yang-Mills theory at strong coupling. We argue that in this
      limit scattering amplitudes map into correlators of twist fields in the two
      dimensional nonlinear O(6) sigma model, similar to those appearing in recent
      studies of entanglement entropy. We provide evidence for this assertion by
      combining the intuition springing from the string world-sheet picture and the
      predictions coming from the operator product expansion series. One of the main
      implications of these considerations is that scattering amplitudes receive
      equally important contributions at strong coupling from both the minimal string
      area and its fluctuations in the sphere. 

PMID- 25615306
TI  - AdS5*S(5) mirror model as a string sigma model.
AB  - Doing a double Wick rotation in the world sheet theory of the light cone
      AdS5*S(5) superstring results in an inequivalent, so-called mirror theory that
      plays a central role in the field of integrability in the AdS-CFT correspondence.
      We show that this mirror theory can be interpreted as the light cone theory of a
      free string on a different background. This background is related to dS5*H(5) by
      a double T-duality, and has hidden supersymmetry. The geometry can also be
      extracted from an integrable deformation of the AdS5*S(5) sigma model, and we
      prove the observed mirror duality of these deformed models at the bosonic level
      as a byproduct. While we focus on AdS5*S(5), our results apply more generally.

PMID- 25615307
TI  - First measurement of neutrino and antineutrino coherent charged pion production
      on argon.
AB  - We report on the first cross section measurements for charged current coherent
      pion production by neutrinos and antineutrinos on argon. These measurements are
      performed using the ArgoNeuT detector exposed to the NuMI beam at Fermilab. The
      cross sections are measured to be 2.6(-1.0)(+1.2)(stat)(-0.4)(+0.3)(syst)*10(-38)
      cm(2)/Ar for neutrinos at a mean energy of 9.6 GeV and 5.5(-2.1)(+2.6)(stat)(
      0.7)(+0.6)(syst)*10(-39)  cm(2)/Ar for antineutrinos at a mean energy of 3.6 GeV.

PMID- 25615309
TI  - Indirect handle on the down-quark Yukawa coupling.
AB  - To measure the Yukawa couplings of the up and down quarks, Yu,d, seems to be far
      beyond the capabilities of current and (near) future experiments in particle
      physics. By performing a general analysis of the potential misalignment between
      quark masses and Yukawa couplings, we derive predictions for the magnitude of
      induced flavor-changing neutral currents (FCNCs), depending on the shift in the
      physical Yukawa coupling of first-generation quarks. We find that a change of
      more than 50% in Yd would generically result in ds transitions in conflict with
      kaon physics. This could already be seen as evidence for a nonvanishing direct
      coupling of the down quark to the newly discovered Higgs boson. The
      nonobservation of certain--already well-constrained--processes is thus turned
      into a powerful indirect measure of otherwise basically unaccessible physical
      parameters of the effective standard model. Similarly, improvements in limits on
      FCNCs in the up-type quark sector can lead to valuable information on Yu.

PMID- 25615308
TI  - Measurement of coherent production of pi(+/-) in neutrino and antineutrino beams
      on carbon from Enu of 1.5 to 20 GeV.
AB  - Neutrino-induced coherent charged pion production on nuclei nuMUA->MU(+/-)pi(?)A
      is a rare, inelastic interaction in which a small squared four-momentum |t| is
      transferred to the recoil nucleus, leaving it intact in the reaction. In the
      scintillator tracker of MINERvA, we remove events with evidence of particles from
      nuclear breakup and reconstruct |t| from the final-state pion and muon. We select
      low |t| events to isolate a sample rich in coherent candidates. By selecting low
      |t| events, we produce a model-independent measurement of the differential cross
      section for coherent scattering of neutrinos and antineutrinos on carbon. We find
      poor agreement with the predicted kinematics in neutrino generators used by
      current oscillation experiments.

PMID- 25615311
TI  - Top quark forward-backward asymmetry in e+ e- annihilation at next-to-next-to
      leading order in QCD.
AB  - We report on a complete calculation of electroweak production of top-quark pairs
      in e+ e- annihilation at next-to-next-to-leading order in quantum chromodynamics.
      Our setup is fully differential in phase space and can be used to calculate any
      infrared-safe observable. Especially we calculated the next-to-next-to-leading
      order corrections to the top-quark forward-backward asymmetry and found sizable
      effects. Our results show a large reduction of the theoretical uncertainties in
      predictions of the forward-backward asymmetry, and allow for a precision
      determination of the top-quark electroweak couplings at future e+ e- colliders.

PMID- 25615315
TI  - Nuclear deformation at finite temperature.
AB  - Deformation, a key concept in our understanding of heavy nuclei, is based on a
      mean-field description that breaks the rotational invariance of the nuclear many
      body Hamiltonian. We present a method to analyze nuclear deformations at finite
      temperature in a framework that preserves rotational invariance. The auxiliary
      field Monte Carlo method is used to generate a statistical ensemble and calculate
      the probability distribution associated with the quadrupole operator. Applying
      the technique to nuclei in the rare-earth region, we identify model-independent
      signatures of deformation and find that deformation effects persist to
      temperatures higher than the spherical-to-deformed shape phase-transition
      temperature of mean-field theory. 

PMID- 25615313
TI  - Nuclear structure aspects of neutrinoless double-beta decay.
AB  - We decompose the neutrinoless double-beta decay matrix elements into sums of
      products over the intermediate nucleus with two less nucleons. We find that the
      sum is dominated by the J(pi)=0(+) ground state of this intermediate nucleus for
      both the light and heavy neutrino decay processes. This provides a new
      theoretical tool for comparing and improving nuclear structure models. It also
      provides the connection to two-nucleon transfer experiments.

PMID- 25615316
TI  - Effects of three-nucleon forces and two-body currents on Gamow-Teller strengths.
AB  - We optimize chiral interactions at next-to-next-to leading order to observables
      in two- and three-nucleon systems and compute Gamow-Teller transitions in 14C and
      (22,24)O using consistent two-body currents. We compute spectra of the daughter
      nuclei 14N and (22,24)F via an isospin-breaking coupled-cluster technique, with
      several predictions. The two-body currents reduce the Ikeda sum rule,
      corresponding to a quenching factor q2~0.84-0.92 of the axial-vector coupling.
      The half-life of 14C depends on the energy of the first excited 1+ state, the
      three-nucleon force, and the two-body current.

PMID- 25615314
TI  - Isomer decay spectroscopy of 164Sm and 166Gd: midshell collectivity around N=100.
AB  - Excited states in the N=102 isotones 166Gd and 164Sm have been observed following
      isomeric decay for the first time at RIBF, RIKEN. The half-lives of the isomeric
      states have been measured to be 950(60) and 600(140) ns for 166Gd and 164Sm,
      respectively. Based on the decay patterns and potential energy surface
      calculations, including beta6 deformation, a spin and parity of 6- has been
      assigned to the isomeric states in both nuclei. Collective observables are
      discussed in light of the systematics of the region, giving insight into nuclear
      shape evolution. The decrease in the ground-band energies of 166Gd and 164Sm
      (N=102) compared to 164Gd and 162Sm (N=100), respectively, presents evidence for
      the predicted deformed shell closure at N=100.

PMID- 25615318
TI  - Measurement of Compton scattering from the deuteron and an improved extraction of
      the neutron electromagnetic polarizabilities.
AB  - The electromagnetic polarizabilities of the nucleon are fundamental properties
      that describe its response to external electric and magnetic fields. They can be
      extracted from Compton-scattering data-and have been, with good accuracy, in the
      case of the proton. In contradistinction, information for the neutron requires
      the use of Compton scattering from nuclear targets. Here, we report a new
      measurement of elastic photon scattering from deuterium using quasimonoenergetic
      tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in
      more than a decade effectively double the world data set. Their energy range
      overlaps with previous experiments and extends it by 20 MeV to higher energies.
      An analysis using chiral effective field theory with dynamical Delta(1232)
      degrees of freedom shows the data are consistent with and within the world data
      set. After demonstrating that the fit is consistent with the Baldin sum rule,
      extracting values for the isoscalar nucleon polarizabilities, and combining them
      with a recent result for the proton, we obtain the neutron polarizabilities as
      alphan=[11.55+/-1.25(stat)+/-0.2(BSR)+/-0.8(th)]*10(-4)  fm(3) and
      betan=[3.65?1.25(stat)+/-0.2(BSR)?0.8(th)]*10(-4)  fm(3), with chi(2)=45.2 for 44
      degrees of freedom.

PMID- 25615319
TI  - Modulation of attosecond beating in resonant two-photon ionization.
AB  - We present a theoretical study of the photoelectron attosecond beating due to
      interference of two-photon transitions in the presence of autoionizing states. We
      show that, as a harmonic traverses a resonance, both the phase shift and
      frequency of the sideband beating significantly vary with photon energy.
      Furthermore, the beating between two resonant paths persists even when the pump
      and the probe pulses do not overlap, thus providing a nonholographic
      interferometric means to reconstruct coherent metastable wave packets. We
      characterize these phenomena by means of a general analytical model that accounts
      for the effect of both intermediate and final resonances on two-photon processes.
      The model predictions are in excellent agreement with those of accurate ab initio
      calculations for the helium atom in the region of the N=2 doubly excited states. 

PMID- 25615320
TI  - Time delays in two-photon ionization.
AB  - We present results of ab initio numerical simulations of time delays in two
      photon ionization of the helium atom using the attosecond streaking technique.
      The temporal shifts in the streaking traces consist of two contributions, namely,
      a time delay acquired during the absorption of the two photons from the extreme
      ultraviolet field and a time delay accumulated by the photoelectron after
      photoabsorption. In the case of a nonresonant transition, the absorption of the
      two photons is found to occur without time delay. In contrast, for a resonant
      transition a substantial absorption time delay is found, which scales linearly
      with the duration of the ionizing pulse. The latter can be related to the phase
      acquired during the transition of the electron from the initial ground state to
      the continuum and the influence of the streaking field on the resonant structure
      of the atom. 

PMID- 25615317
TI  - Fission barrier of superheavy nuclei and persistence of shell effects at high
      spin: cases of 254No and 220Th.
AB  - We report on the first measurement of the fission barrier height in a heavy shell
      stabilized nucleus. The fission barrier height of 254No is measured to be
      Bf=6.0+/-0.5  MeV at spin 15h and, by extrapolation, Bf=6.6+/-0.9  MeV at spin
      0h. This information is deduced from the measured distribution of entry points in
      the excitation energy versus spin plane. The same measurement is performed for
      220Th and only a lower limit of the fission barrier height can be determined:
      Bf(I)>8  MeV. Comparisons with theoretical fission barriers test theories that
      predict properties of superheavy elements.

PMID- 25615310
TI  - Measurement of the single top quark production cross section and |Vtb| in events
      with one charged lepton, large missing transverse energy, and jets at CDF.
AB  - We report a measurement of single top quark production in proton-antiproton
      collisions at a center-of-mass energy of sqrt[s]=1.96  TeV using a data set
      corresponding to 7.5  fb(-1) of integrated luminosity collected by the Collider
      Detector at Fermilab. We select events consistent with the single top quark decay
      process t->Wb->lnub by requiring the presence of an electron or muon, a large
      imbalance of transverse momentum indicating the presence of a neutrino, and two
      or three jets including at least one originating from a bottom quark. An
      artificial neural network is used to discriminate the signal from backgrounds. We
      measure a single top quark production cross section of 3.04(-0.53)(+0.57)  pb and
      set a lower limit on the magnitude of the coupling between the top quark and
      bottom quark |Vtb|>0.78 at the 95% credibility level.

PMID- 25615321
TI  - Photon emission and absorption of a single ion coupled to an optical-fiber
      cavity.
AB  - We present a light-matter interface which consists of a single 174Yb+ ion coupled
      to an optical fiber cavity. We observe that photons at 935 nm are mainly emitted
      into the cavity mode and that correlations between the polarization of the photon
      and the spin state of the ion are preserved despite the intrinsic coupling into a
      single-mode fiber. Complementary, when a faint coherent light field is injected
      into the cavity mode, we find enhanced and polarization dependent absorption by
      the ion.

PMID- 25615322
TI  - Is the molecular Berry phase an artifact of the Born-Oppenheimer approximation?
AB  - We demonstrate that the molecular Berry phase and the corresponding
      nonanalyticity in the electronic Born-Oppenheimer wave function is, in general,
      not a true topological feature of the exact solution of the full electron-nuclear
      Schrodinger equation. For a numerically exactly solvable model we show that a
      nonanalyticity, and the associated geometric phase, only appear in the limit of
      infinite nuclear mass, while a perfectly smooth behavior is found for any finite
      nuclear mass. 

PMID- 25615323
TI  - Photon momentum sharing between an electron and an ion in photoionization: from
      one-photon (photoelectric effect) to multiphoton absorption.
AB  - We investigate photon-momentum sharing between an electron and an ion following
      different photoionization regimes. We find very different partitioning of the
      photon momentum in one-photon ionization (the photoelectric effect) as compared
      to multiphoton processes. In the photoelectric effect, the electron acquires a
      momentum that is much greater than the single photon momentum homega/c [up to
      (8/5) homega/c] whereas in the strong-field ionization regime, the photoelectron
      only acquires the momentum corresponding to the photons absorbed above the field
      free ionization threshold plus a momentum corresponding to a fraction (3/10) of
      the ionization potential Ip. In both cases, due to the smallness of the electron
      ion mass ratio, the ion takes nearly the entire momentum of all absorbed N
      photons (via the electron-ion center of mass). Additionally, the ion takes, as a
      recoil, the photoelectron momentum resulting from mutual electron-ion interaction
      in the electromagnetic field. Consequently, the momentum partitioning of the
      photofragments is very different in both regimes. This suggests that there is a
      rich, unexplored physics to be studied between these two limits which can be
      generated with current ultrafast laser technology.

PMID- 25615324
TI  - CP-violating effect of the Th nuclear magnetic quadrupole moment: accurate many
      body study of ThO.
AB  - Investigations of CP violation in the hadron sector may be done using
      measurements in the ThO molecule. Recent measurements in this molecule improved
      the limit on the electron electric dipole moment (EDM) by an order of magnitude.
      Another time-reversal (T) and parity (P)-violating effect in 229ThO is induced by
      the nuclear magnetic quadrupole moment. We perform nuclear and molecular
      calculations to express this effect in terms of the strength constants of T, P
      odd nuclear forces, neutron EDM, QCD vacuum angle theta, quark EDM, and chromo
      EDM.

PMID- 25615325
TI  - Fine structure and ionization energy of the 1s2s2p 4P state of the helium
      negative ion He-.
AB  - The fine structure and ionization energy of the 1s2s2p (4)P state of the helium
      negative ion He(-) are calculated in Hylleraas coordinates, including
      relativistic and QED corrections up to O(alpha(4)mc(2)), O((MU/M)alpha(4)mc(2)),
      O(alpha(5)mc(2)), and O((MU/M)alpha(5)mc(2)). Higher order corrections are
      estimated for the ionization energy. A comparison is made with other calculations
      and experiments. We find that the present results for the fine structure
      splittings agree with experiment very well. However, the calculated ionization
      energy deviates from the experimental result by about 1 standard deviation. The
      estimated theoretical uncertainty in the ionization energy is much less than the
      experimental accuracy.

PMID- 25615326
TI  - Anisotropic relaxation dynamics in a dipolar Fermi gas driven out of equilibrium.
AB  - We report on the observation of a large anisotropy in the rethermalization
      dynamics of an ultracold dipolar Fermi gas driven out of equilibrium. Our system
      consists of an ultracold sample of strongly magnetic 167Er fermions, spin
      polarized in the lowest Zeeman sublevel. In this system, elastic collisions arise
      purely from universal dipolar scattering. Based on cross-dimensional
      rethermalization experiments, we observe a strong anisotropy of the scattering,
      which manifests itself in a large angular dependence of the thermal relaxation
      dynamics. Our result is in good agreement with recent theoretical predictions.
      Furthermore, we measure the rethermalization rate as a function of temperature
      for different angles and find that the suppression of collisions by Pauli
      blocking is not influenced by the dipole orientation.

PMID- 25615327
TI  - High-resolution imaging of velocity-controlled molecular collisions using
      counterpropagating beams.
AB  - We present ultrahigh-resolution measurements of state-to-state inelastic
      differential cross sections for NO-Ne and NO-Ar collisions, obtained by combining
      the Stark deceleration and velocity map imaging techniques. We show that for
      counterpropagating crossed beam geometries, the effect of the velocity spreads of
      the reagent beams on the angular resolution of the images is minimized.
      Furthermore, the counterpropagating geometry results in images that are symmetric
      with respect to the relative velocity vector. This allows for the use of inverse
      Abel transformation methods that enhance the resolution further. State-resolved
      diffraction oscillations in the differential cross sections are measured with an
      angular resolution approaching 0.3 degrees . Distinct structures observed in the
      cross sections gauge the quality of recent ab initio potential energy surfaces
      for NO-rare-gas atom collisions with unprecedented precision. 

PMID- 25615328
TI  - Size-dependent high-order harmonic generation in rare-gas clusters.
AB  - High-order harmonic generation (HHG) is investigated in rare-gas clusters as a
      function of the cluster size using 0.8 and 1.3  MUm femtosecond lasers. A
      characteristic, species-dependent knee structure in the single particle response
      is observed. A 1D recollision model qualitatively reproduces this behavior and
      associates it to the degree of delocalization of the initial wave function. Small
      clusters are observed to have a higher efficiency than monomers but rapidly lose
      this advantage as the size increases. The implications of these findings on the
      HHG mechanism in clusters are discussed. 

PMID- 25615329
TI  - All-optical formation of coherent dark states of silicon-vacancy spins in
      diamond.
AB  - Spin impurities in diamond can be versatile tools for a wide range of solid-state
      based quantum technologies, but finding spin impurities that offer sufficient
      quality in both photonic and spin properties remains a challenge for this
      pursuit. The silicon-vacancy center has recently attracted much interest because
      of its spin-accessible optical transitions and the quality of its optical
      spectrum. Complementing these properties, spin coherence is essential for the
      suitability of this center as a spin-photon quantum interface. Here, we report
      all-optical generation of coherent superpositions of spin states in the ground
      state of a negatively charged silicon-vacancy center using coherent population
      trapping. Our measurements reveal a characteristic spin coherence time, T2*,
      exceeding 45 nanoseconds at 4 K. We further investigate the role of phonon
      mediated coupling between orbital states as a source of irreversible decoherence.
      Our results indicate the feasibility of all-optical coherent control of silicon
      vacancy spins using ultrafast laser pulses.

PMID- 25615330
TI  - All-optical initialization, readout, and coherent preparation of single silicon
      vacancy spins in diamond.
AB  - The silicon-vacancy (SiV-) color center in diamond has attracted attention
      because of its unique optical properties. It exhibits spectral stability and
      indistinguishability that facilitate efficient generation of photons capable of
      demonstrating quantum interference. Here we show optical initialization and
      readout of electronic spin in a single SiV- center with a spin relaxation time of
      T1=2.4+/-0.2  ms. Coherent population trapping (CPT) is used to demonstrate
      coherent preparation of dark superposition states with a spin coherence time of
      T2?=35+/-3  ns. This is fundamentally limited by orbital relaxation, and an
      understanding of this process opens the way to extend coherence by engineering
      interactions with phonons. Hyperfine structure is observed in CPT measurements
      with the 29Si isotope which allows access to nuclear spin. These results
      establish the SiV- center as a solid-state spin-photon interface.

PMID- 25615331
TI  - Generation and detection of a sub-Poissonian atom number distribution in a one
      dimensional optical lattice.
AB  - We demonstrate preparation and detection of an atom number distribution in a one
      dimensional atomic lattice with the variance -14  dB below the Poissonian noise
      level. A mesoscopic ensemble containing a few thousand atoms is trapped in the
      evanescent field of a nanofiber. The atom number is measured through dual-color
      homodyne interferometry with a pW-power shot noise limited probe. Strong coupling
      of the evanescent probe guided by the nanofiber allows for a real-time
      measurement with a precision of +/-8  atoms on an ensemble of some 10(3)  atoms
      in a one-dimensional trap. The method is very well suited for generating
      collective atomic entangled or spin-squeezed states via a quantum nondemolition
      measurement as well as for tomography of exotic atomic states in a one
      dimensional lattice.

PMID- 25615332
TI  - Scattering in the ultrastrong regime: nonlinear optics with one photon.
AB  - The scattering of a flying photon by a two-level system ultrastrongly coupled to
      a one-dimensional photonic waveguide is studied numerically. The photonic medium
      is modeled as an array of coupled cavities and the whole system is analyzed
      beyond the rotating wave approximation using matrix product states. It is found
      that the scattering is strongly influenced by the single- and multiphoton dressed
      bound states present in the system. In the ultrastrong coupling regime a new
      channel for inelastic scattering appears, where an incident photon deposits
      energy into the qubit, exciting a photon-bound state, and escaping with a lower
      frequency. This single-photon nonlinear frequency conversion process can reach up
      to 50% efficiency. Other remarkable features in the scattering induced by
      counterrotating terms are a blueshift of the reflection resonance and a Fano
      resonance due to long-lived excited states. 

PMID- 25615333
TI  - Large suppression of quantum fluctuations of light from a single emitter by an
      optical nanostructure.
AB  - We investigate the reduction of the electromagnetic field fluctuations in
      resonance fluorescence from a single emitter coupled to an optical nanostructure.
      We find that such hybrid systems can lead to the creation of squeezed states of
      light, with quantum fluctuations significantly below the shot-noise level.
      Moreover, the physical conditions for achieving squeezing are strongly relaxed
      with respect to an emitter in free space. A high degree of control over squeezed
      light is feasible both in the far and near fields, opening the pathway to its
      manipulation and applications on the nanoscale with state-of-the-art setups. 

PMID- 25615334
TI  - Directional superradiant emission from statistically independent incoherent
      nonclassical and classical sources.
AB  - Superradiance has been an outstanding problem in quantum optics since Dicke
      introduced the concept of enhanced directional spontaneous emission by an
      ensemble of identical two-level atoms. The effect is based on the correlated
      collective Dicke states which turn out to be highly entangled. Here we show that
      enhanced directional emission of spontaneous radiation can be produced also with
      statistically independent incoherent sources, via the measurement of higher-order
      correlation functions of the emitted radiation. Our analysis is applicable to a
      wide variety of quantum emitters, like trapped atoms, ions, quantum dots, or
      nitrogen-vacancy centers, and is also valid for incoherent classical emitters.
      This is experimentally confirmed with up to eight statistically independent
      thermal light sources. The arrangement to measure the higher-order correlation
      functions corresponds to a generalized Hanbury Brown-Twiss setup, demonstrating
      that the two phenomena, superradiance and the Hanbury Brown-Twiss effect, stem
      from the same interference phenomenon. 

PMID- 25615335
TI  - Harnessing the point-spread function for high-resolution far-field optical
      microscopy.
AB  - The resolution limit of far-field optical microscopy is reexamined with a full
      vectorial theoretical analysis. A highly symmetric excitation optical field and
      optimized detection scheme are proposed to harness the total point-spread
      function for a microscopic system. Spatial resolution of better than 1/6lambda is
      shown to be obtainable, giving rise to a resolution better than 100 nm with
      visible light excitation. The experimental measurement is applied to examine
      nonfluorescent samples. A lateral resolution of 1/5lambda is obtained in truly
      far-field optical microscopy with a working distance greater than ~500lambda.
      Comparison is made for the far-field microscopic measurement with that of a
      nearfield scanning optical microscopy, showing that the proposed scheme provides
      a better image quality. 

PMID- 25615336
TI  - Hybrid coupling mechanism in a system supporting high order diffraction,
      plasmonic, and cavity resonances.
AB  - The interactions between plasmonic and photonic modes of a cavity-coupled
      plasmonic crystal are studied in diffraction and diffractionless regimes, which
      lead us to the understanding of coherent interactions between electron plasma,
      higher order cavity, and diffraction modes. The strong interaction between
      plasmonic and photonic modes is shown to enhance as well as suppress surface
      plasmon resonance based on cavity phase relation. Numerical and analytical
      approaches are developed to accurately explain the physics of the interactions
      evident in their characteristic dispersion graphs. Further experimental
      measurements confirm the theoretical predictions. 

PMID- 25615337
TI  - Imaging optical fields through heavily scattering media.
AB  - Coherent imaging and communication through or within heavily scattering random
      media has been considered impossible due to the randomization of the information
      contained in the scattered electromagnetic field. We report a remarkable result
      based on speckle correlations over incident field position that demonstrates that
      the field incident on a heavily scattering random medium can be obtained using a
      method that is not restricted to weak scatter and is, in principle, independent
      of the thickness of the scattering medium. Natural motion can be exploited, and
      the approach can be extended to other geometries. The near-infrared optical
      results presented indicate that the approach is applicable to other frequency
      regimes, as well as other wave types. This work presents opportunities to enhance
      communication channel capacity in the large source and detector number regime,
      for a new method to view binary stars from Earth, and in biomedical applications.

PMID- 25615338
TI  - Ionization-induced self-compression of tightly focused femtosecond laser pulses.
AB  - As lasers become progressively higher in power, optical damage thresholds will
      become a limiting factor. Using the nonlinear optics of plasma may be a way to
      circumvent these limits. Here, we present a new self-compression mechanism for
      high-power, femtosecond laser pulses based on geometrical focusing and three
      dimensional spatiotemporal reshaping in an ionizing plasma. By propagating
      tightly focused, 10-mJ femtosecond laser pulses through a 100-MUm gas jet, the
      interplay between ionization gradients, focusing, and diffraction of the light
      pulse leads to stable and uniform self-compression of the pulse, while
      maintaining a high-energy throughput and excellent refocusability. Self
      compression down to 16 fs from an original 36-fs pulse is measured using second
      harmonic-generation frequency-resolved optical gating. Using this mechanism, we
      are able to maintain a high transmission (>88%) such that the pulse peak power is
      doubled. Three-dimensional numerical simulations are performed to support our
      interpretation of the experimental observations. 

PMID- 25615339
TI  - Unidirectional spectral singularities.
AB  - We propose a class of spectral singularities emerging from the coincidence of two
      independent singularities with highly directional responses. These spectral
      singularities result from resonance trapping induced by the interplay between
      parity-time symmetry and Fano resonances. At these singularities, while the
      system is reciprocal in terms of a finite transmission, a simultaneous infinite
      reflection from one side and zero reflection from the opposite side can be
      realized. 

PMID- 25615340
TI  - Spectral noise correlations of an ultrafast frequency comb.
AB  - Cavity-based noise detection schemes are combined with ultrafast pulse shaping as
      a means to diagnose the spectral correlations of both the amplitude and phase
      noise of an ultrafast frequency comb. The comb is divided into ten spectral
      regions, and the distribution of noise as well as the correlations between all
      pairs of spectral regions are measured against the quantum limit. These
      correlations are then represented in the form of classical noise matrices, which
      furnish a complete description of the underlying comb dynamics. Their
      eigendecomposition reveals a set of theoretically predicted, decoupled noise
      modes that govern the dynamics of the comb. These matrices also contain the
      information necessary to deduce macroscopic noise properties of the comb. 

PMID- 25615342
TI  - Forecasting transitions in systems with high-dimensional stochastic complex
      dynamics: a linear stability analysis of the tangled nature model.
AB  - We propose a new procedure to monitor and forecast the onset of transitions in
      high-dimensional complex systems. We describe our procedure by an application to
      the tangled nature model of evolutionary ecology. The quasistable configurations
      of the full stochastic dynamics are taken as input for a stability analysis by
      means of the deterministic mean-field equations. Numerical analysis of the high
      dimensional stability matrix allows us to identify unstable directions associated
      with eigenvalues with a positive real part. The overlap of the instantaneous
      configuration vector of the full stochastic system with the eigenvectors of the
      unstable directions of the deterministic mean-field approximation is found to be
      a good early warning of the transitions occurring intermittently. 

PMID- 25615341
TI  - Twisted toroidal vortex solitons in inhomogeneous media with repulsive
      nonlinearity.
AB  - Toroidal modes in the form of so-called Hopfions, with two independent winding
      numbers, a hidden one (twist s), which characterizes a circular vortex thread
      embedded into a three-dimensional soliton, and the vorticity around the vertical
      axis (m), appear in many fields, including field theory, ferromagnetics, and semi
      and superconductors. Such topological states are normally generated in
      multicomponent systems, or as trapped quasilinear modes in toroidal potentials.
      We uncover that stable solitons with this structure can be created, without any
      linear potential, in the single-component setting with the strength of repulsive
      nonlinearity growing fast enough from the center to the periphery, for both steep
      and smooth modulation profiles. Toroidal modes with s=1 and vorticity m=0, 1, 2
      are produced. They are stable for m<=1, and do not exist for s>1. An approximate
      analytical solution is obtained for the twisted ring with s=1, m=0. Under the
      application of an external torque, it rotates like a solid ring. The setting can
      be implemented in a Bose-Einstein condensate (BEC) by means of the Feshbach
      resonance controlled by inhomogeneous magnetic fields. 

PMID- 25615343
TI  - Fluctuations of global energy release and crackling in nominally brittle
      heterogeneous fracture.
AB  - The temporal evolution of mechanical energy and spatially averaged crack speed
      are both monitored in slowly fracturing artificial rocks. Both signals display an
      irregular burstlike dynamics, with power-law distributed fluctuations spanning a
      broad range of scales. Yet, the elastic power released at each time step is
      proportional to the global velocity all along the process, which enables defining
      a material-constant fracture energy. We characterize the intermittent dynamics by
      computing the burst statistics. This latter displays the scale-free features
      signature of crackling dynamics, in qualitative but not quantitative agreement
      with the depinning interface models derived for fracture problems. The possible
      sources of discrepancies are pointed out and discussed. 

PMID- 25615344
TI  - Planar-dielectric-wakefield accelerator structure using Bragg-reflector
      boundaries.
AB  - We report experimental measurements of narrow-band, single-mode excitation, and
      drive beam energy modulation, in a dielectric wakefield accelerating structure
      with planar geometry and Bragg-reflector boundaries. A short, relativistic
      electron beam (~1  ps) with moderate charge (~100  pC) is used to drive the
      wakefields in the structure. The fundamental mode of the structure is reinforced
      by constructive interference in the alternating dielectric layers at the
      boundary, and is characterized by the spectral analysis of the emitted coherent
      Cherenkov radiation signal. Data analysis shows a narrow-band peak at 210 GHz
      corresponding to the fundamental mode of the structure. Simulations in both 2D
      and 3D provide insight into the propagating fields and reproduction of the
      electron beams dynamics observables and emitted radiation characteristics. 

PMID- 25615345
TI  - Experimental proof of adjustable single-knob ion beam emittance partitioning.
AB  - The performance of accelerators profits from phase-space tailoring by coupling of
      degrees of freedom. Previously applied techniques swap the emittances among the
      three degrees but the set of available emittances is fixed. In contrast to these
      emittance exchange scenarios, the emittance transfer scenario presented here
      allows for arbitrarily changing the set of emittances as long as the product of
      the emittances is preserved. This Letter is the first experimental demonstration
      of transverse emittance transfer along an ion beam line. The amount of transfer
      is chosen by setting just one single magnetic field value. The envelope functions
      (beta) and slopes (alpha) of the finally uncorrelated and repartitioned beam at
      the exit of the transfer line do not depend on the amount of transfer. 

PMID- 25615346
TI  - Spatiotemporal splitting of global eigenmodes due to cross-field coupling via
      vortex dynamics in drift wave turbulence.
AB  - Spatiotemporal splitting events of drift wave (DW) eigenmodes due to nonlinear
      coupling are investigated in a cylindrical helicon plasma device. DW eigenmodes
      in the radial-azimuthal cross section have been experimentally observed to split
      at radial locations and recombine into the global eigenmode with a time shorter
      than the typical DW period (t?fDW(-1)). The number of splits correlates with the
      increase of turbulence. The observed dynamics can be theoretically reproduced by
      a Kuramoto-type model of a network of radially coupled azimuthal eigenmodes.
      Coupling by E*B-vortex convection cell dynamics and ion gyro radii motion leads
      to cross-field synchronization and occasional mode splitting events.

PMID- 25615347
TI  - Number fluctuations of a dipolar condensate: anisotropy and slow approach to the
      thermodynamic regime.
AB  - We present a theory for the number fluctuations of a quasi-two-dimensional (quasi
      2D) dipolar Bose-Einstein condensate measured with finite resolution cells. We
      show that when the dipoles are tilted to have a component parallel to the plane
      of the trap, the number fluctuations become anisotropic, i.e., depend on the in
      plane orientation of the measurement cell. We develop analytic results for the
      quantum and thermal fluctuations applicable to the cell sizes accessible in
      experiments. We show that as cell size is increased the thermodynamic fluctuation
      result is approached much more slowly than in condensates with short range
      interactions, so experiments would not require high numerical aperture imaging to
      observe the predicted effect. 

PMID- 25615348
TI  - Thermal phase transitions of strongly correlated bosons with spin-orbit coupling.
AB  - Experiments on ultracold atoms have started to explore lattice effects and
      thermal fluctuations for two-component bosons with spin-orbit coupling (SOC).
      Motivated by this, we derive and study a tJ model for lattice bosons with equal
      Rashba-Dresselhaus SOC and strong Hubbard repulsion in a uniform Zeeman magnetic
      field. Using the Gutzwiller ansatz, we find strongly correlated ground states
      with stripe superfluid (SF) order. We formulate a finite temperature
      generalization of the Gutzwiller method, and show that thermal fluctuations in
      the doped Mott insulator drive a two-step melting of the stripe SF, revealing a
      wide regime of a stripe normal fluid. 

PMID- 25615349
TI  - Dynamic nuclear polarization of high-density atomic hydrogen in solid mixtures of
      molecular hydrogen isotopes.
AB  - We report on magnetic resonance studies of high-density atomic hydrogen and
      deuterium in solid hydrogen matrices at temperatures below 1 K. Average
      concentrations of H atoms ~3*10(19)  cm(-3) are obtained in chemical tunneling
      reactions of isotope exchange with D atoms. The products of these reactions are
      closely located pairs of H atoms near D2 molecules with strong exchange
      interactions. We discovered a dynamic nuclear polarization effect on H atoms
      created by pumping the center of the H electron spin resonance spectrum, similar
      to the Overhauser effect in metals. Our results indicate that H atoms may be
      arranged inside molecular matrices at separations equivalent to local
      concentrations of 2.6*10(21)  cm(-3). This opens up a way to build a metallic
      state of atomic hydrogen at zero pressure.

PMID- 25615350
TI  - Quasiparticle lifetime in a mixture of Bose and Fermi superfluids.
AB  - In this Letter, we study the effect of quasiparticle interactions in a Bose-Fermi
      superfluid mixture. We consider the lifetime of a quasiparticle of the Bose
      superfluid due to its interaction with quasiparticles in the Fermi superfluid. We
      find that this damping rate, i.e., the inverse of the lifetime, has quite a
      different threshold behavior at the BCS and the BEC side of the Fermi superfluid.
      The damping rate is a constant near the threshold momentum in the BCS side, while
      it increases rapidly in the BEC side. This is because, in the BCS side, the decay
      process is restricted by the constraint that the fermion quasiparticle is located
      near the Fermi surface, while such a restriction does not exist in the BEC side
      where the damping process is dominated by bosonic quasiparticles of the Fermi
      superfluid. Our results are related to the collective mode experiment in the
      recently realized Bose-Fermi superfluid mixture. 

PMID- 25615351
TI  - Theory of electrocaloric effect in a shape-changing container: gas in a nanotube.
AB  - Driven by applied voltage or Ohmic heating, bistable nanotubes filled with gas
      can transform between expanded and collapsed configurations and by doing so
      convert energy between mechanical, electrical, and thermal forms. The
      electrocaloric response, a reversible change of temperature in response to
      applied voltage, combines the advantages of a working fluid with the lack of
      internal interfaces characteristic of robust solid-state thermoelectric devices.
      Such devices could be constructed from any conductive two-dimensional atomically
      thin material wrapped into an appropriate geometry. 

PMID- 25615352
TI  - Static and dynamic aspects of black silicon formation.
AB  - We present a combination of experimental data and modeling that explains some of
      the important characteristics of black silicon (BSi) developed in cryogenic
      reactive ion etching (RIE) processes, including static properties (dependence of
      resulting topography on process parameters) and dynamic aspects (evolution of
      topography with process time). We generate a phase diagram predicting the RIE
      parameter combinations giving rise to different BSi geometries and show that the
      topographic details of BSi explain the metamaterial characteristics that are
      responsible for its low reflectivity. In particular, the unique combination of
      needle and hole features of various heights and depths, which is captured by our
      model and confirmed by focused ion beam nanotomography, creates a uniquely smooth
      transition in refractive index. The model also correctly describes dynamical
      characteristics, such as the dependence of aspect ratio on process time, and the
      prediction of new etching fronts appearing at topographical saddle points during
      the incipient stages of BSi development--a phenomenon reported here for the first
      time.

PMID- 25615353
TI  - Intermittent dislocation density fluctuations in crystal plasticity from a phase
      field crystal model.
AB  - Plastic deformation mediated by collective dislocation dynamics is investigated
      in the two-dimensional phase-field crystal model of sheared single crystals. We
      find that intermittent fluctuations in the dislocation population number
      accompany bursts in the plastic strain-rate fluctuations. Dislocation number
      fluctuations exhibit a power-law spectral density 1/f2 at high frequencies f. The
      probability distribution of number fluctuations becomes bimodal at low driving
      rates corresponding to a scenario where low density of defects alternates at
      irregular times with high populations of defects. We propose a simple stochastic
      model of dislocation reaction kinetics that is able to capture these statistical
      properties of the dislocation density fluctuations as a function of shear rate.

PMID- 25615354
TI  - New iron hydrides under high pressure.
AB  - The Fe-H system has been investigated by combined x-ray diffraction studies and
      total energy calculations at pressures up to 136 GPa. The experiments involve
      laser annealing of hydrogen-embedded iron in a diamond anvil cell. Two new FeHx
      compounds, with x~2 and x=3, are discovered at 67 and 86 GPa, respectively. Their
      crystal structures are identified (unit cell and Fe positional parameters from x
      ray diffraction, H positional parameters from ab initio calculations) as
      tetragonal with space group I4/mmm for FeH(~2) and as simple cubic with space
      group Pm3m for FeH3. Large metastability regimes are observed that allowed to
      measure the P(V) equation of state at room temperature of FeH, FeH(~2), and FeH3.

PMID- 25615355
TI  - Shape-memory transformations of NiTi: minimum-energy pathways between austenite,
      martensites, and kinetically limited intermediate states.
AB  - NiTi is the most used shape-memory alloy; nonetheless, a lack of understanding
      remains regarding the associated structures and transitions, including their
      barriers. Using a generalized solid-state nudged elastic band method implemented
      via density-functional theory, we detail the structural transformations in NiTi
      relevant to shape memory: those between a body-centered orthorhombic (bco) ground
      state and a newly identified stable austenite ("glassy" B2-like) structure,
      including energy barriers (hysteresis) and intermediate structures (observed as a
      kinetically limited R phase), and between martensite variants (bco orientations).
      All results are in good agreement with available experiment. We contrast the
      austenite results to those from the often-assumed, but unstable B2. These high-
      and low-temperature structures and structural transformations provide much needed
      atomic-scale detail for transitions responsible for NiTi shape-memory effects. 

PMID- 25615356
TI  - First-order dynamical phase transitions.
AB  - Recently, dynamical phase transitions have been identified based on the
      nonanalytic behavior of the Loschmidt echo in the thermodynamic limit [Heyl et
      al., Phys. Rev. Lett. 110, 135704 (2013)]. By introducing conditional probability
      amplitudes, we show how dynamical phase transitions can be further classified,
      both mathematically, and potentially in experiment. This leads to the definition
      of first-order dynamical phase transitions. Furthermore, we develop a generalized
      Keldysh formalism which allows us to use nonequilibrium dynamical mean-field
      theory to study the Loschmidt echo and dynamical phase transitions in high
      dimensional, nonintegrable models. We find dynamical phase transitions of first
      order in the Falicov-Kimball model and in the Hubbard model. 

PMID- 25615357
TI  - Origin of the phonon Hall effect in rare-earth garnets.
AB  - The phonon Hall effect has been observed in the paramagnetic insulator Tb3Gd5O12.
      A magnetic field applied perpendicularly to a heat current induces a temperature
      gradient that is perpendicular to both the field and the current. We show that
      this effect is due to resonant skew scattering of phonons from the crystal field
      states of superstoichiometric Tb(3+) ions. This scattering originates from the
      coupling between the quadrupole moment of Tb(3+) ions and the lattice strain. The
      estimated magnitude of the effect is consistent with experimental observations at
      T~5  K and can be significantly enhanced by increasing temperature.

PMID- 25615358
TI  - New reconstructions of the (110) surface of rutile TiO2 predicted by an
      evolutionary method.
AB  - Reconstructions of the (110) surface of rutile TiO2 (the dominant surface of this
      important mineral and catalyst) are investigated using the evolutionary approach,
      resolving previous controversies. Depending on thermodynamic conditions, four
      different stable reconstructions are observed for this surface. We confirm the
      recently proposed "Ti2O3-(1*2)" and "Ti2O-(1*2)" reconstructions and predict two
      new reconstructions "Ti3O2-(1*2)" and "Ti3O3-(2*1)," which match experimental
      results. Furthermore, we find that surface electronic states are sensitive to
      reconstructions and, therefore, depend on thermodynamic conditions.

PMID- 25615359
TI  - Detection of spin entanglement via spin-charge separation in crossed Tomonaga
      Luttinger liquids.
AB  - We investigate tunneling between two spinful Tomonaga-Luttinger liquids (TLLs)
      realized, e.g., as two crossed nanowires or quantum Hall edge states. When
      injecting into each TLL one electron of opposite spin, the dc current measured
      after the crossing differs for singlet, triplet, or product states. This is a
      striking new non-Fermi liquid feature because the (mean) current in a
      noninteracting beam splitter is insensitive to spin entanglement. It can be
      understood in terms of collective excitations subject to spin-charge separation.
      This behavior may offer an easier alternative to traditional entanglement
      detection schemes based on current noise, which we show to be suppressed by the
      interactions. 

PMID- 25615360
TI  - Effect of spin-orbit interactions on the 0.7 anomaly in quantum point contacts.
AB  - We study how the conductance of a quantum point contact is affected by spin-orbit
      interactions, for systems at zero temperature both with and without electron
      electron interactions. In the presence of spin-orbit coupling, tuning the
      strength and direction of an external magnetic field can change the dispersion
      relation and hence the local density of states in the point contact region. This
      modifies the effect of electron-electron interactions, implying striking changes
      in the shape of the 0.7-anomaly and introducing additional distinctive features
      in the first conductance step. 

PMID- 25615361
TI  - Dynamical correlations and screened exchange on the experimental bench: spectral
      properties of the cobalt pnictide BaCo2As2.
AB  - Understanding the Fermi surface and low-energy excitations of iron or cobalt
      pnictides is crucial for assessing electronic instabilities such as magnetic or
      superconducting states. Here, we propose and implement a new approach to compute
      the low-energy properties of correlated electron materials, taking into account
      both screened exchange beyond the local density approximation and local dynamical
      correlations. The scheme allows us to resolve the puzzle of BaCo2As2, for which
      standard electronic structure techniques predict a ferromagnetic instability not
      observed in nature.

PMID- 25615362
TI  - Supersolid phase accompanied by a quantum critical point in the intermediate
      coupling regime of the Holstein model.
AB  - We reveal that electron-phonon systems described by the Holstein model on a
      bipartite lattice exhibit, away from half filling, a supersolid (SS) phase
      characterized by coexisting charge order (CO) and superconductivity (SC), and an
      accompanying quantum critical point (QCP). The SS phase, demonstrated by the
      dynamical mean-field theory with a quantum Monte Carlo impurity solver, emerges
      in the intermediate-coupling regime, where the peak of the Tc dome is located and
      the metal-insulator crossover occurs. On the other hand, in the weak- and strong
      coupling regimes the CO-SC boundary is of first order with no intervening SS
      phases. The QCP is associated with the continuous transition from SS to SC and
      characterized by a reentrant behavior of the SS around it. We further show that
      the SS-SC transition is hallmarked by diverging charge fluctuations and a kink
      (peak) in the superfluid density.

PMID- 25615363
TI  - Symmetry of the excitations in the hidden order state of URu2Si2.
AB  - We perform polarized electronic Raman scattering on URu2Si2 single crystals at
      low temperature down to 8 K in the hidden-order state and under a magnetic field
      up to 10 T. The hidden-order state is characterized by a sharp excitation at 1.7
      meV and a gap in the electronic continuum below 6.8 meV. Both Raman signatures
      are of pure A2g symmetry. By comparing the behavior of the Raman sharp excitation
      and the neutron resonance at Q0=(0,0,1), we provide new evidence, constrained by
      selection rules of the two probes, that the hidden-order state breaks the
      translational symmetry along the c axis such that Gamma and Z points fold on top
      of each other. The observation of these distinct Raman features with a peculiar
      A2g symmetry as a signature of the hidden-order phase places strong constraints
      on current theories of the hidden-order in URu2Si2.

PMID- 25615364
TI  - Dimerization-induced Fermi-surface reconstruction in IrTe2.
AB  - We report a de Haas-van Alphen (dHvA) oscillation study on IrTe2 single crystals
      showing complex dimer formations. By comparing the angle dependence of dHvA
      oscillations with band structure calculations, we show distinct Fermi surface
      reconstruction induced by a 1/5-type and a 1/8-type dimerizations. This verifies
      that an intriguing quasi-two-dimensional conducting plane across the layers is
      induced by dimerization in both cases. A phase transition to the 1/8 phase with
      higher dimer density reveals that local instabilities associated with intra- and
      interdimer couplings are the main driving force for complex dimer formations in
      IrTe2.

PMID- 25615365
TI  - Correlation-induced self-doping in the iron-pnictide superconductor
      Ba2Ti2Fe2As4O.
AB  - The electronic structure of the iron-based superconductor Ba2Ti2Fe2As4O
      (Tc(onset)=23.5  K) has been investigated by using angle-resolved photoemission
      spectroscopy and combined local density approximation and dynamical mean field
      theory calculations. The electronic states near the Fermi level are dominated by
      both the Fe 3d and Ti 3d orbitals, indicating that the spacer layers separating
      different FeAs layers are also metallic. By counting the enclosed volumes of the
      Fermi surface sheets, we observe a large self-doping effect; i.e., 0.25 electrons
      per unit cell are transferred from the FeAs layer to the Ti2As2O layer, leaving
      the FeAs layer in a hole-doped state. This exotic behavior is successfully
      reproduced by our dynamical mean field calculations, in which the self-doping
      effect is attributed to the electronic correlations in the 3d shells. Our work
      provides an alternative route of effective doping without element substitution
      for iron-based superconductors.

PMID- 25615366
TI  - Resonant edge magnetoplasmons and their decay in graphene.
AB  - We investigate resonant edge magnetoplasmons (EMPs) and their decay in graphene
      by high-frequency electronic measurements. From EMP resonances in disk shaped
      graphene, we show that the dispersion relation of EMPs is nonlinear due to
      interactions, giving rise to the intrinsic decay of EMP wave packets. We also
      identify extrinsic dissipation mechanisms due to interaction with localized
      states in bulk graphene from the decay time of EMP wave packets. We indicate
      that, owing to the linear band structure and the sharp edge potential, EMP
      dissipation in graphene can be lower than that in GaAs systems. 

PMID- 25615367
TI  - Paramagnetic spin pumping.
AB  - We have demonstrated spin pumping from a paramagnetic state of an insulator
      La2NiMnO6 into a Pt film. Single-crystalline films of La2NiMnO6 which exhibit a
      ferromagnetic order at TC~270  K were grown by pulsed laser deposition. The
      inverse spin Hall voltage induced by spin-current injection has been observed in
      the Pt layer not only in the ferromagnetic phase of La2NiMnO6, but also in a wide
      temperature range above TC. The efficient spin pumping in the paramagnetic phase
      is ascribable to ferromagnetic correlation, not to ferromagnetic order.

PMID- 25615368
TI  - Gilbert damping in noncollinear ferromagnets.
AB  - The precession and damping of a collinear magnetization displaced from its
      equilibrium are well described by the Landau-Lifshitz-Gilbert equation. The
      theoretical and experimental complexity of noncollinear magnetizations is such
      that it is not known how the damping is modified by the noncollinearity. We use
      first-principles scattering theory to investigate transverse domain walls (DWs)
      of the important ferromagnetic alloy Ni80Fe20 and show that the damping depends
      not only on the magnetization texture but also on the specific dynamic modes of
      Bloch and Neel DWs in ways that were not theoretically predicted. Even in the
      highly disordered Ni80Fe20 alloy, the damping is found to be remarkably nonlocal.

PMID- 25615369
TI  - Multiterminal conductance of a Floquet topological insulator.
AB  - We report on simulations of the dc conductance and quantum Hall response of a
      Floquet topological insulator using Floquet scattering theory. Our results reveal
      that laser-induced edge states lead to quantum Hall plateaus once imperfect
      matching with the nonilluminated leads is lessened. The magnitude of the Hall
      plateaus, however, is not directly related to the number and chirality of all the
      edge states at a given energy, as usual. Instead, the plateaus are dominated by
      those edge states adding to the time-averaged density of states. Therefore, the
      dc quantum Hall conductance of a Floquet topological insulator is not directly
      linked to topological invariants of the full Floquet bands. 

PMID- 25615370
TI  - Density-curvature response and gravitational anomaly.
AB  - We study constraints imposed by the Galilean invariance on linear electromagnetic
      and elastic responses of two-dimensional gapped systems in a background magnetic
      field. Exact relations between response functions following from the Ward
      identities are derived. In addition to the viscosity-conductivity relations known
      in the literature, we find new relations between the density-curvature response
      and the thermal Hall response. 

PMID- 25615371
TI  - Nonequilibrated counterpropagating edge modes in the fractional quantum Hall
      regime.
AB  - It is well established that density reconstruction at the edge of a two
      dimensional electron gas takes place for hole-conjugate states in the fractional
      quantum Hall effect (such as v=2/3, 3/5, etc.). Such reconstruction leads, after
      equilibration between counterpropagating edge channels, to a downstream chiral
      current edge mode accompanied by upstream chiral neutral modes (carrying energy
      without net charge). Short equilibration length prevented thus far observation of
      the counterpropagating current channels-the hallmark of density reconstruction.
      Here, we provide evidence for such nonequilibrated counterpropagating current
      channels, in short regions (l=4  MUm and l=0.4  MUm) of fractional filling v=2/3
      and, unexpectedly, v=1/3, sandwiched between two regions of integer filling v=1.
      Rather than a two-terminal fractional conductance, the conductance exhibited a
      significant ascension towards unity quantum conductance (GQ=e(2)/h) at or near
      the fractional plateaus. We attribute this conductance rise to the presence of a
      nonequilibrated channel in the fractional short regions.

PMID- 25615372
TI  - Valley splitting and polarization by the Zeeman effect in monolayer MoSe2.
AB  - We have measured circularly polarized photoluminescence in monolayer MoSe2 under
      perpendicular magnetic fields up to 10 T. At low doping densities, the neutral
      and charged excitons shift linearly with field strength at a rate of ?0.12  meV/T
      for emission arising, respectively, from the K and K' valleys. The opposite sign
      for emission from different valleys demonstrates lifting of the valley
      degeneracy. The magnitude of the Zeeman shift agrees with predicted magnetic
      moments for carriers in the conduction and valence bands. The relative intensity
      of neutral and charged exciton emission is modified by the magnetic field,
      reflecting the creation of field-induced valley polarization. At high doping
      levels, the Zeeman shift of the charged exciton increases to ?0.18  meV/T. This
      enhancement is attributed to many-body effects on the binding energy of the
      charged excitons.

PMID- 25615373
TI  - Time-domain interferometry of surface plasmons at nonlinear continuum hot spots
      in films of silver nanoparticles.
AB  - Nonlinear continuum generation from diffraction-limited hot spots in rough silver
      films exhibits striking narrow-band intensity resonances in excitation
      wavelength. Time-domain Fourier spectroscopy uncovers how these resonances arise
      due to the formation of a "plasmon staircase", a discreteness in the fundamental
      oscillation of the plasmon excitations responsible for generating the white-light
      continuum. Whereas multiple scattering from discrete antennas can be invoked to
      explain hot spot formation in random assemblies of isolated particles, hot spots
      in films of fused nanoparticles are excited by interfering propagating surface
      plasmons, launched by scattering from individual nanoparticle antennas. For
      closed films, discrete propagating plasmons interact coherently over distances of
      tens of microns to pump the hot spot. 

PMID- 25615374
TI  - Persistent ferromagnetism and topological phase transition at the interface of a
      superconductor and a topological insulator.
AB  - At the interface of an s-wave superconductor and a three-dimensional topological
      insulator, Majorana zero modes and Majorana helical states have been proposed to
      exist respectively around magnetic vortices and geometrical edges. Here we first
      show that randomly distributed magnetic impurities at such an interface will
      induce bound states that broaden into impurity bands inside (but near the edges
      of) the superconducting gap, which remains open unless the impurity concentration
      is too high. Next we find that an increase in the superconducting gap suppresses
      both the oscillation magnitude and the period of the Ruderman-Kittel-Kasuya
      Yosida interaction between two magnetic impurities. Within a mean-field
      approximation, the ferromagnetic Curie temperature is found to be essentially
      independent of the superconducting gap, an intriguing phenomenon due to a
      compensation effect between the short-range ferromagnetic and long-range
      antiferromagnetic interactions. The existence of robust superconductivity and
      persistent ferromagnetism at the interface allows realization of a novel
      topological phase transition from a nonchiral to a chiral superconducting state
      at sufficiently low temperatures, providing a new platform for topological
      quantum computation. 

PMID- 25615375
TI  - Heavy-fermion superconductivity in the quadrupole ordered state of PrV2Al20.
AB  - PrV2Al20 is a rare example of a heavy-fermion system based on strong
      hybridization between conduction electrons and nonmagnetic quadrupolar moments of
      the cubic Gamma3 ground doublet. Here, we report that a high-quality single
      crystal of PrV2Al20 exhibits superconductivity at Tc=50  mK in the
      antiferroquadrupole-ordered state under ambient pressure. The heavy-fermion
      character of the superconductivity is evident from the specific heat jump of
      DeltaC/T~0.3  J/mol K(2) and the effective mass m*/m0~140 estimated from the
      temperature dependence of the upper critical field. Furthermore, the high-quality
      single crystals exhibit double transitions at TQ=0.75  K and T*=0.65  K
      associated with quadrupole and octupole degrees of freedom of the Gamma3 doublet.
      In the ordered state, the specific heat C/T shows a T(3) dependence, indicating
      the gapless mode associated with the quadrupole order, the octupole order, or
      both. The strong sensitivity to impurity of the superconductivity suggests
      unconventional character due to significant quadrupolar fluctuations.

PMID- 25615376
TI  - Many-body characterization of particle-conserving topological superfluids.
AB  - What distinguishes trivial superfluids from topological superfluids in
      interacting many-body systems where the number of particles is conserved?
      Building on a class of integrable pairing Hamiltonians, we present a number
      conserving, interacting variation of the Kitaev model, the Richardson-Gaudin
      Kitaev chain, that remains exactly solvable for periodic and antiperiodic
      boundary conditions. Our model allows us to identify fermion parity switches that
      distinctively characterize topological superconductivity (fermion superfluidity)
      in generic interacting many-body systems. Although the Majorana zero modes in
      this model have only a power-law confinement, we may still define many-body
      Majorana operators by tuning the flux to a fermion parity switch. We derive a
      closed-form expression for an interacting topological invariant and show that the
      transition away from the topological phase is of third order. 

PMID- 25615377
TI  - Anyonic liquids in nearly saturated spin chains.
AB  - Most Heisenberg-like spin chains flow to a universal free-fermion fixed point
      near the magnetic-field induced saturation point. Here, we show that an exotic
      fixed point, characterized by two species of low-energy excitations with mutual
      anyonic statistics, may also emerge in such spin chains if the dispersion
      relation has two minima. By using bosonization, two-magnon exact calculations,
      and numerical density-matrix-renormalization-group calculations, we demonstrate
      the existence of this anyonic-liquid fixed point in an xxz spin chain with up to
      second-neighbor interactions. We also identify a range of microscopic parameters,
      which support this phase. 

PMID- 25615378
TI  - Reversible control of Co magnetism by voltage-induced oxidation.
AB  - We demonstrate that magnetic properties of ultrathin Co films adjacent to Gd2O3
      gate oxides can be directly manipulated by voltage. The Co films can be
      reversibly changed from an optimally oxidized state with a strong perpendicular
      magnetic anisotropy to a metallic state with an in-plane magnetic anisotropy or
      to an oxidized state with nearly zero magnetization, depending on the polarity
      and time duration of the applied electric fields. Consequently, an
      unprecedentedly large change of magnetic anisotropy energy up to 0.73 erg/cm(2)
      has been realized in a nonvolatile manner using gate voltages of only a few
      volts. These results open a new route to achieve ultralow energy magnetization
      manipulation in spintronic devices.

PMID- 25615379
TI  - Elastic stiffness of a Skyrmion crystal.
AB  - We observe the elastic stiffness and ultrasonic absorption of a Skyrmion crystal
      in the chiral-lattice magnet MnSi. The Skyrmion crystal lattice exhibits a
      stiffness 3 orders of magnitude smaller than that of the atomic lattice of MnSi,
      being as soft as the flux line lattice in type-II superconductors. The observed
      anisotropic elastic responses are consistent with the cylindrical shape of the
      Skyrmion spin texture. Phenomenological analysis reveals that the spin-orbit
      coupling is responsible for the emergence of anisotropic elasticity in the
      Skyrmion lattice. 

PMID- 25615380
TI  - Haldane phase in the Hubbard model at 2/3-filling for the organic molecular
      compound Mo3S7(dmit)3.
AB  - We report the discovery of a correlated insulator with a bulk gap at 2/3 filling
      in a geometrically frustrated Hubbard model that describes the low-energy physics
      of Mo3S7(dmit)3. This is very different from the Mott insulator expected at half
      filling. We show that the insulating phase, which persists even for very weak
      electron-electron interactions (U), is adiabatically connected to the Haldane
      phase and is consistent with experiments on Mo3S7(dmit)3.

PMID- 25615381
TI  - Incipient ferromagnetism in Tb2Ge2O7: application of chemical pressure to the
      enigmatic spin-liquid compound Tb2Ti2O7.
AB  - After nearly 20 years of study, the origin of the spin-liquid state in Tb2Ti2O7
      remains a challenge for experimentalists and theorists alike. To improve our
      understanding of the exotic magnetism in Tb2Ti2O7, we synthesize a chemical
      pressure analog: Tb2Ge2O7. Substitution of titanium by germanium results in a
      lattice contraction and enhanced exchange interactions. We characterize the
      magnetic ground state of Tb2Ge2O7 with specific heat, ac and dc magnetic
      susceptibility, and polarized neutron scattering measurements. Akin to Tb2Ti2O7,
      there is no long-range order in Tb2Ge2O7 down to 20 mK. The Weiss temperature of 
      19.2(1)  K, which is more negative than that of Tb2Ti2O7, supports the picture of
      stronger antiferromagnetic exchange. Polarized neutron scattering of Tb2Ge2O7
      reveals that liquidlike correlations dominate in this system at 3.5 K. However,
      below 1 K, the liquidlike correlations give way to intense short-range
      ferromagnetic correlations with a length scale similar to the Tb-Tb nearest
      neighbor distance. Despite stronger antiferromagnetic exchange, the ground state
      of Tb2Ge2O7 has ferromagnetic character, in stark contrast to the pressure
      induced antiferromagnetic order observed in Tb2Ti2O7.

PMID- 25615382
TI  - Microscopic realization of two-dimensional bosonic topological insulators.
AB  - It is well known that a bosonic Mott insulator can be realized by condensing
      vortices of a boson condensate. Usually, a vortex becomes an antivortex (and vice
      versa) under time reversal symmetry, and the condensation of vortices results in
      a trivial Mott insulator. However, if each vortex or antivortex interacts with a
      spin trapped at its core, the time reversal transformation of the composite
      vortex operator will contain an extra minus sign. It turns out that such a
      composite vortex condensed state is a bosonic topological insulator (BTI) with
      gapless boundary excitations protected by U(1)?Z2(T) symmetry. We point out that
      in BTI, an external pi-flux monodromy defect carries a Kramers doublet. We
      propose lattice model Hamiltonians to realize the BTI phase, which might be
      implemented in cold atom systems or spin-1 solid state systems.

PMID- 25615383
TI  - Fast electrical control of single electron spins in quantum dots with vanishing
      influence from nuclear spins.
AB  - We demonstrate fast universal electrical spin manipulation with inhomogeneous
      magnetic fields. With fast Rabi frequency up to 127 MHz, we leave the
      conventional regime of strong nuclear-spin influence and observe a spin-flip
      fidelity >96%, a distinct chevron Rabi pattern in the spectral-time domain, and a
      spin resonance linewidth limited by the Rabi frequency, not by the dephasing
      rate. In addition, we establish fast z rotations up to 54 MHz by directly
      controlling the spin phase. Our findings will significantly facilitate tomography
      and error correction with electron spins in quantum dots. 

PMID- 25615384
TI  - Duality of topological defects in hexagonal manganites.
AB  - We show that the spontaneous symmetry breaking in multiferroic hexagonal
      manganites can be chemically manipulated to yield two complementary ground
      states: the well-known ferroelectric P6(3)cm and an antipolar P3c phase. Both
      symmetry breakings yield topologically protected vortex defects, with the
      antipolar vortices dual to those of the ferroelectric. This duality stems from
      the existence of 12 possible angles of MnO5 tilting, and broad strain-free walls
      with low energy spontaneously emerge through an intermediate P3c1 state,
      providing a complete unified symmetry description.

PMID- 25615385
TI  - Dynamic screening probed by core-resonant double photoemission from surfaces.
AB  - The universal response of a sudden created core hole, predicted to occur on an
      attosecond (10(-18)  s) time scale, lacks an experimental demonstration. With a
      two-dimensional coincidence spectrometer, we demonstrate an extensive energy
      sharing between the Ag 4p photoelectron and the N2,3VV Auger electron exceeding
      10 eV. This energy width provides access to the time scale of the emission
      process. This is the fingerprint of the dynamic fluctuation process 4p(-1)?4d(
      2)4f. The shakeup induced interband transitions from the Ag(100) surface are also
      identified by comparing the coincidence spectrum with the M4,5VV Auger
      transitions.

PMID- 25615386
TI  - Inductive measurement of optically hyperpolarized phosphorous donor nuclei in an
      isotopically enriched silicon-28 crystal.
AB  - We experimentally demonstrate the first inductive readout of optically
      hyperpolarized phosphorus-31 donor nuclear spins in an isotopically enriched
      silicon-28 crystal. The concentration of phosphorus donors in the crystal was
      1.5*10(15)  cm(-3), 3 orders of magnitude lower than has previously been detected
      via direct inductive detection. The signal-to-noise ratio measured in a single
      free induction decay from a 1  cm(3) sample (~10(15) spins) was 113. By
      transferring the sample to an X-band ESR spectrometer, we were able to obtain a
      lower bound for the nuclear spin polarization at 1.7 K of ~64%. The (31)P-T2
      measured with a Hahn echo sequence was 420 ms at 1.7 K, which was extended to 1.2
      s with a Carr Purcell cycle. The T1 of the (31)P nuclear spins at 1.7 K is
      extremely long and could not be determined, as no decay was observed even on a
      time scale of 4.5 h. Optical excitation was performed with a 1047 nm laser, which
      provided above-band-gap excitation of the silicon. The buildup of the
      hyperpolarization at 4.2 K followed a single exponential with a characteristic
      time of 577 s, while the buildup at 1.7 K showed biexponential behavior with
      characteristic time constants of 578 and 5670 s.

PMID- 25615387
TI  - Contact formation in random networks of elongated objects.
AB  - The effect of steric hindrance is an important aspect of granular packings as it
      gives rise to, e.g., limitations on the densities of ordered and disordered
      packings, both of which are essentially defined by the geometry of the
      constituents. Here we focus on the random packing of rods via deposition and
      their distributions of contact number and segment length. Such statistical
      properties are relevant for mechanical properties of the structures, but the
      (quite large) steric effects on them have not been addressed in previous studies.
      We therefore develop a theory that describes the statistical properties of rod
      packings, while taking into account that the deposited rods cannot overlap and
      thus induce steric hindrances. The distributions derived from the theory are
      compared with experimental results and numerical simulations of networks
      constructed via deposition. The results explain the non-Poisson statistics
      observed in the experiments and show that the induced steric range of the rods
      can be large compared to their diameter and decreases with compactification of
      the pile, implying local orientational ordering of the structure. 

PMID- 25615388
TI  - Microscopic theory for negative differential mobility in crowded environments.
AB  - We study the behavior of the stationary velocity of a driven particle in an
      environment of mobile hard-core obstacles. Based on a lattice gas model, we
      demonstrate analytically that the drift velocity can exhibit a nonmonotonic
      dependence on the applied force, and show quantitatively that such negative
      differential mobility (NDM), observed in various physical contexts, is controlled
      by both the density and diffusion time scale of the obstacles. Our study unifies
      recent numerical and analytical results obtained in specific regimes, and makes
      it possible to determine analytically the region of the full parameter space
      where NDM occurs. These results suggest that NDM could be a generic feature of
      biased (or active) transport in crowded environments. 

PMID- 25615389
TI  - Filling an emulsion drop with motile bacteria.
AB  - We have measured the spatial distribution of motile Escherichia coli inside
      spherical water droplets emulsified in oil. At low cell concentrations, the cell
      density peaks at the water-oil interface; at increasing concentration, the bulk
      of each droplet fills up uniformly while the surface peak remains. Simulations
      and theory show that the bulk density results from a "traffic" of cells leaving
      the surface layer, increasingly due to cell-cell scattering as the surface
      coverage rises above ~10%. Our findings show similarities with the physics of a
      rarefied gas in a spherical cavity with attractive walls. 

PMID- 25615390
TI  - Universal behavior in the mesoscale properties of amyloid fibrils.
AB  - Amyloid fibrils are ubiquitous proteinaceous aggregates occurring in vivo and in
      vitro, with an invariant structural fingerprint at the molecular length scale.
      However, interpretation of their mesoscopic architectures is complicated by
      diverse observable polymorphic states. We here present a constitutive model for
      amyloid fibrils based on the minimization of the total energy per fibril. The
      model is benchmarked on real amyloid fibrils studied by atomic force microscopy.
      We use multistranded beta-lactoglobulin amyloid fibrils as a model system
      exhibiting a rich polymorphism. The constitutive model quantitatively
      recapitulates the main mesoscopic topological features of amyloid fibrils, that
      is, the evolution of fibril periodicity as a function of the ionic strength of
      the solution and of the fibril width. A universal mesoscopic structural signature
      of the fibrils emerges from this picture, predicting a general, parameter-free
      law for the periodicity of the fibrils, that depends solely on the number of
      protofilaments per fibril. These predictions are validated experimentally and
      conclusively highlight the role of competing electrostatic and elastic
      contributions as the main players in the establishment of amyloid fibrils
      structure. 

PMID- 25615391
TI  - Dynamic compression of single nanochannel confined DNA via a nanodozer assay.
AB  - We show that a single DNA molecule confined and extended in a nanochannel can be
      dynamically compressed by sliding a permeable gasket at a fixed velocity relative
      to the stationary polymer. The gasket is realized experimentally by optically
      trapping a nanosphere inside a nanochannel. The trapped bead acts like a
      "nanodozer," directly applying compressive forces to the molecule without
      requirement of chemical attachment. Remarkably, these strongly nonequilibrium
      measurements can be quantified via a simple nonlinear convective-diffusion
      formalism and yield insights into the local blob statistics, allowing us to
      conclude that the compressed nanochannel-confined chain exhibits mean-field
      behavior. 

PMID- 25615392
TI  - Exact distributions for stochastic gene expression models with bursting and
      feedback.
AB  - Stochasticity in gene expression can give rise to fluctuations in protein levels
      and lead to phenotypic variation across a population of genetically identical
      cells. Recent experiments indicate that bursting and feedback mechanisms play
      important roles in controlling noise in gene expression and phenotypic variation.
      A quantitative understanding of the impact of these factors requires analysis of
      the corresponding stochastic models. However, for stochastic models of gene
      expression with feedback and bursting, exact analytical results for protein
      distributions have not been obtained so far. Here, we analyze a model of gene
      expression with bursting and feedback regulation and obtain exact results for the
      corresponding protein steady-state distribution. The results obtained provide new
      insights into the role of bursting and feedback in noise regulation and
      optimization. Furthermore, for a specific choice of parameters, the system
      studied maps on to a two-state biochemical switch driven by a bursty input noise
      source. The analytical results derived provide quantitative insights into diverse
      cellular processes involving noise in gene expression and biochemical switching. 

PMID- 25615393
TI  - Thermophoretic forces on DNA measured with a single-molecule spring balance.
AB  - We stretch a single DNA molecule with thermophoretic forces and measure these
      forces with a spring balance: the DNA molecule itself. It is an entropic spring
      which we calibrate, using as a benchmark its Brownian motion in the nanochannel
      that contains and prestretches it. This direct measurement of the thermophoretic
      force in a static configuration finds forces up to 130 fN. This is eleven times
      stronger than the force experienced by the same molecule in the same thermal
      gradient in bulk, where the molecule shields itself. Our stronger forces stretch
      the middle of the molecule up to 80% of its contour length. We find the Soret
      coefficient per unit length of DNA at various ionic strengths. It agrees, with
      novel precision, with results obtained in bulk for DNA too short to shield itself
      and with the thermodynamic model of thermophoresis. 

PMID- 25615394
TI  - Interactions between charged lamellae in aqueous solution.
AB  - Interactions between charged surfaces in aqueous solutions, widespread in soft
      matter and biology, are very complex and, despite many efforts, their full
      explanation remains challenging. We support the idea that, in contrast to
      extremely small separations (d<=2  nm), where many effects, prominently those
      linked to the structure of liquid water, interfere, electrostatics alone rules
      over larger distances (d>=5  nm) at low ionic strength. We set up specially
      designed surface force apparatus (SFA) experiments to measure the elastic
      compressibility modulus of a stack of charged membranes with monovalent
      counterions, directly and with high precision. We demonstrate that electrostatics
      alone, if implemented beyond Poisson-Boltzmann theory, fully accounts for the
      data, nonelectrostatic contributions playing at best a minor role. 

PMID- 25615395
TI  - Direct visualization of conformation and dense packing of DNA-based soft
      colloids.
AB  - Soft colloids--such as polymer-coated particles, star polymers, block-copolymer
      micelles, microgels--constitute a broad class of materials where microscopic
      properties such as deformability and penetrability of the particle play a key
      role in tailoring their macroscopic properties which is of interest in many
      technological areas. The ability to access these microscopic properties is not
      yet demonstrated despite its great importance. Here we introduce novel DNA-coated
      colloids with star-shaped architecture that allows accessing the above local
      structural information by directly visualizing their intramolecular monomer
      density profile and arm's free-end locations with confocal fluorescent
      microscopy. Compression experiments on a two-dimensional hexagonal lattice formed
      by these macromolecular assemblies reveal an exceptional resistance to mutual
      interpenetration of their charged corona at pressures approaching the MPa range.
      Furthermore, we find that this lattice, in a close packing configuration, is
      surprisingly tolerant to particle size variation. We anticipate that these
      stimuli-responsive materials could aid to get deeper insight in a wide range of
      problems in soft matter, including the study and design of biomimetic lubricated
      surfaces.

PMID- 25615396
TI  - Boosting capacitive blue-energy and desalination devices with waste heat.
AB  - We show that sustainably harvesting "blue" energy from the spontaneous mixing
      process of fresh and salty water can be boosted by varying the water temperature
      during a capacitive mixing process. Our modified Poisson-Boltzmann calculations
      predict a strong temperature dependence of the electrostatic potential of a
      charged electrode in contact with an adjacent aqueous 1:1 electrolyte. We propose
      to exploit this dependence to boost the efficiency of capacitive blue engines,
      which are based on cyclically charging and discharging nanoporous supercapacitors
      immersed in salty and fresh water, respectively [D. Brogioli, Phys. Rev. Lett.
      103, 058501 (2009)]. We show that the energy output of blue engines can be
      increased by a factor of order 2 if warm (waste-heated) fresh water is mixed with
      cold sea water. Moreover, the underlying physics can also be used to optimize the
      reverse process of capacitive desalination of water. 

PMID- 25615397
TI  - Anomalous impact in reaction-diffusion financial models.
AB  - We generalize the reaction-diffusion model A+B->0 in order to study the impact of
      an excess of A (or B) at the reaction front. We provide an exact solution of the
      model, which shows that the linear response breaks down: the average displacement
      of the reaction front grows as the square root of the imbalance. We argue that
      this model provides a highly simplified but generic framework to understand the
      square-root impact of large orders in financial markets.

PMID- 25615398
TI  - Thermodynamic analysis of anion and cation effects on the keto-enol equilibrium
      in ionic liquids. A comparative study with conventional solvents.
AB  - A comparative thermodynamic investigation of the keto-enol interconversion
      reaction has been performed in several organic solvents and room-temperature
      ionic liquids (RTILs) to evaluate the role of the solvent and the effect of the
      ionic composition of RTILs. The tautomeric constant (KT) values at different
      temperatures have been analyzed in terms of the van't Hoff relationship to give
      the relevant thermodynamic parameters. The DeltaG degrees  values are the results
      of quite different combinations of the DeltaH degrees  and DeltaS degrees  values
      depending on the nature of the solvent. As expected, in conventional solvents,
      the tautomeric equilibrium is enthalpically disfavored and entropically favored
      by the increase in solvent polarity. In ionic liquids, the nature of the anion
      seems to play a primary role in the thermodynamics of the reaction that is
      endothermic and enthalpically driven in PF6- and TF2N-based RTILs and exothermic
      but entropically driven in BF4-based RTILs. The cation effect on the
      thermodynamics of the reaction is more complex and is consistent with a
      prevalence of the alkyl side chain segregation in the organization of the ILs. 

PMID- 25615399
TI  - Surrogate-driven deformable motion model for organ motion tracking in particle
      radiation therapy.
AB  - The aim of this study is the development and experimental testing of a tumor
      tracking method for particle radiation therapy, providing the daily respiratory
      dynamics of the patient's thoraco-abdominal anatomy as a function of an external
      surface surrogate combined with an a priori motion model. The proposed tracking
      approach is based on a patient-specific breathing motion model, estimated from
      the four-dimensional (4D) planning computed tomography (CT) through deformable
      image registration. The model is adapted to the interfraction baseline variations
      in the patient's anatomical configuration. The driving amplitude and phase
      parameters are obtained intrafractionally from a respiratory surrogate signal
      derived from the external surface displacement. The developed technique was
      assessed on a dataset of seven lung cancer patients, who underwent two repeated
      4D CT scans. The first 4D CT was used to build the respiratory motion model,
      which was tested on the second scan. The geometric accuracy in localizing lung
      lesions, mediated over all breathing phases, ranged between 0.6 and 1.7 mm across
      all patients. Errors in tracking the surrounding organs at risk, such as lungs,
      trachea and esophagus, were lower than 1.3 mm on average. The median absolute
      variation in water equivalent path length (WEL) within the target volume did not
      exceed 1.9 mm-WEL for simulated particle beams. A significant improvement was
      achieved compared with error compensation based on standard rigid alignment. The
      present work can be regarded as a feasibility study for the potential extension
      of tumor tracking techniques in particle treatments. Differently from current
      tracking methods applied in conventional radiotherapy, the proposed approach
      allows for the dynamic localization of all anatomical structures scanned in the
      planning CT, thus providing complete information on density and WEL variations
      required for particle beam range adaptation.

PMID- 25615400
TI  - TOP1 gene copy numbers are increased in cancers of the bile duct and pancreas.
AB  - BACKGROUND: Bile duct and pancreatic cancer (PC) have poor prognoses and
      treatment options for inoperable patients are scarce. In order to improve outcome
      for these patients, there is an urgent need for biomarkers predictive of
      treatment effect. Irinotecan is a topoisomerase 1 (Top1) poison. Top1 protein,
      TOP1 gene copy number and mRNA expression, respectively, have been proposed as
      predictive biomarkers of response to irinotecan in other cancers. Here we
      investigate the occurrence of TOP1 gene aberrations in cancers of the bile ducts
      and pancreas. MATERIAL AND METHODS: TOP1 and centromere 20 (CEN-20) numbers were
      investigated by fluorescence in situ hybridization analyses in tumor tissue from
      226 patients. The frequencies of aberration in the TOP1 gene copy number, the CEN
      20 copy number and the TOP1/CEN-20 ratio were analyzed. As TOP1 is located on
      chromosome 20, the CEN-20 probe was included to distinguish between chromosomal
      and gene amplifications. RESULTS: In PC, 29.8% had an increased TOP1 copy number
      (>= 3.5n gene copies per cell) and 10.8% had a TOP1/CEN-20 ratio >1.5. In bile
      duct cancer, 12.8 % had an increased TOP1 copy number and 6.4% had a TOP1/CEN-20
      ratio >1.5. Neither the TOP1 copy number nor the TOP1/CEN-20 ratios could predict
      overall survival. CONCLUSION: We here report that a substantial number of
      patients with bile duct or PC have increased TOP1 copy number and increased
      TOP1/CEN-20 ratio making further analyses on the association between TOP1 gene
      copy number and irinotecan efficacy clinically relevant.

PMID- 25615401
TI  - New thoughts on the "forgotten" aspect of antimicrobial stewardship: adverse
      event reporting.
AB  - Antimicrobial stewardship is an activity that optimizes patient care through
      selection of the most appropriate antimicrobial therapy. Antimicrobial
      stewardship programs strive to enhance patient care and reduce preventable
      consequences of antimicrobial use. They are also vital in monitoring for the
      development of adverse events occurring as a result of antimicrobial therapy,
      although literature reviews of this activity are scarce. Although randomized
      controlled trials are considered the gold standard to study the efficacy of a
      medication, these trials are not designed to test safety end points and often are
      only able to identify the most commonly occurring and acute adverse events. In
      addition, prior to a drug going to market, it is difficult to detect rare adverse
      events because the associated costs are economically untenable given the limited
      pipeline of novel agents. These limitations in some ways may be resolved with the
      use of postmarketing surveillance and spontaneous reporting systems such as the
      United States Food and Drug Administration Adverse Event Reporting System. The
      focus of this commentary is to highlight the importance of adverse event
      reporting by antimicrobial stewardship programs to spontaneous reporting systems
      as a means to improve patient care. 

PMID- 25615402
TI  - Effects of timing and severity of salinity stress on rice (Oryza sativa L.)
      yield, grain composition, and starch functionality.
AB  - The aim of this work was to examine agronomic, compositional, and functional
      changes in rice (Oryza sativa L. cv. Nipponbare) grains from plants grown under
      low-to-moderate salinity stress in the greenhouse. Plants were grown in sodium
      chloride-containing soil (2 or 4 dS/m(2) electrical conductivity), which was
      imposed 4-weeks after transplant (called Seedling EC2 and EC4) or after the
      appearance of the anthers (called Anthesis EC2 and EC4). The former simulates
      field conditions while the latter permits observation of the isolated effect of
      salt on grain filling processes. Key findings of this study are the following:
      (i) Plants showed adaptive responses to prolonged salt treatment with no negative
      effects on grain weight or fertility. Seedling EC2 plants had more panicles and
      enhanced caryopsis dimensions, while surprisingly, Seedling EC4 plants did not
      differ from the control group in the agronomic parameters measured. (ii) Grain
      starch increased in Seedling EC4 (32.6%) and Anthesis EC2 (39%), respectively,
      suggesting a stimulatory effect of salt on starch accumulation. (iii) The
      salinity treatment of 2 dS/m(2) was better tolerated at anthesis than the 4
      dS/m(2) treatment as the latter led to reduced grain weight (28.8%) and seed
      fertility (19.4%) and compensatory increases in protein (20.1%) and nitrogen
      (19.8%) contents. (iv) Although some salinity treatments led to changes in starch
      content, these did not alter starch fine structure, morphology, or composition.
      We observed no differences in reducing sugar and amylose content or starch
      granule size distribution among any of the treatments. The only alterations in
      starch were limited to small changes in thermal properties and glucan chain
      distribution, which were only seen in the Anthesis EC4 treatment. This similarity
      of compositional and functional features was supported by multivariate analysis
      of all variables measured, which suggested that differences due to treatments
      were minimal. Overall, this study documents the specific response of rice under
      defined conditions, and illustrates that the plasticity of plant response to mild
      stress is complex and highly context-dependent, even under greenhouse conditions
      in which other potential environmental stress impacts are minimized. 

PMID- 25615403
TI  - Effects of once weekly NMES training on knee extensors fatigue and body
      composition in a person with spinal cord injury.
AB  - STUDY DESIGN: Single-subject case (male, 33 years of age, T6 SCI AIS A).
      OBJECTIVES: To determine the effect of surface neuromuscular electrical
      stimulation (NMES) training conducted once weekly on improving fatigue resistance
      as well as regional and whole body composition in an individual with spinal cord
      injury (SCI). SETTING: Laboratory setting within a SCI Center. METHODS: Surface
      NMES resistance training (RT) of the paralyzed knee extensors was conducted once
      weekly for 12 weeks using ankle weights. Knee extensor fatigue index was
      determined by the number of repetitions (reps) achieved out of 30 reps. Total and
      regional body composition including percentage body fat (%BF), fat mass (FM),
      lean mass (LM) were conducted before the first session and one week after the
      last training session using whole-body dual-energy X-ray absorptiometry. RESULTS:
      The participant had a compliance rate of 83% and he was able to lift 6 and 2 lbs
      on the right and left legs, respectively. Right knee extensors showed greater
      fatigue resistance compared to the left one. Leg LM increased by 6% accompanied
      with decrease in arm, trunk and total body LM by -4.7%, -13%, -5%, respectively.
      The %BF increased by 8%, 7.3%, 15.5%, 11.5% for arm, legs, trunk and total body.
      CONCLUSION: Once weekly of NMES RT evokes local positive changes in leg LM
      without reciprocating the continuous loss in LM or gain in FM in other regions
      and total body. Training was effective in increasing strength as well as fatigue
      resistance of the trained knee extensors.

PMID- 25615404
TI  - A theoretical and experimental study of the NMR spectra of 4,5,6,7
      tetrafluorobenzazoles with special stress on PCM calculations of chemical shifts.
AB  - The chemical shifts and several (19)F-(19)F, (13)C-(19) F and (1)H-(19)F spin
      spin coupling constants (SSCSs) of eight 4,5,6,7-tetraflurobenzazoles (three
      benzimidazoles, three benzimidazolinones and two indazoles) have been determined.
      The chemical shifts were discussed using gauge including atomic orbital-density
      functional theory calculations taking into account solvent effects (polarizable
      continuum model) and, for the solid state, hydrogen bonds (clusters up to three
      molecules).

PMID- 25615405
TI  - Brushite foams--the effect of Tween(r) 80 and Pluronic(r) F-127 on foam porosity
      and mechanical properties.
AB  - Resorbable calcium phosphate based bone void fillers should work as temporary
      templates for new bone formation. The incorporation of macropores with sizes of
      100 -300 um has been shown to increase the resorption rate of the implant and
      speed up bone ingrowth. In this work, macroporous brushite cements were
      fabricated through foaming of the cement paste, using two different synthetic
      surfactants, Tween(r) 80 and Pluronic(r) F-127. The macropores formed in the
      Pluronic samples were both smaller and less homogeneously distributed compared
      with the pores formed in the Tween samples. The porosity and compressive strength
      (CS) were comparable to previously developed hydroxyapatite foams. The cement
      foam containing Tween, 0.5M citric acid in the liquid, 1 mass% of disodium
      dihydrogen pyrophosphate mixed in the powder and a liquid to powder ratio of 0.43
      mL/g, showed the highest porosity values (76% total and 56% macroporosity), while
      the CS was >1 MPa, that is, the hardened cement could be handled without rupture
      of the foamed structure. The investigated brushite foams show potential for
      future clinical use, both as bone void fillers and as scaffolds for in vitro bone
      regeneration.

PMID- 25615406
TI  - Enhanced characterization of oil sands acid-extractable organics fractions using
      electrospray ionization-high-resolution mass spectrometry and synchronous
      fluorescence spectroscopy.
AB  - The open pit oil sands mining operations north of Fort McMurray, Alberta, Canada,
      are accumulating tailings waste at a rate approximately equal to 4.9 million m(3)
      /d. Naphthenic acids are among the most toxic components within tailings to
      aquatic life, but structural components have largely remained unidentified. In
      the present study, electrospray ionization high-resolution mass spectrometry (ESI
      HRMS) and synchronous fluorescence spectroscopy (SFS) were used to characterize
      fractions derived from the distillation of an acid-extractable organics (AEO)
      mixture isolated from oil sands process-affected water (OSPW). Mean molecular
      weights of each fraction, and their relative proportions to the whole AEO
      extract, were as follows: fraction 1: 237 Da, 8.3%; fraction 2: 240 Da, 23.8%;
      fraction 3: 257 Da, 26.7%; fraction 4: 308 Da, 18.9%; fraction 5: 355 Da, 10.0%.
      With increasing mean molecular weight of the AEO fractions, a concurrent increase
      occurred in the relative abundance of nitrogen-, sulfur-, and oxygen-containing
      ions, double-bond equivalents, and degree of aromaticity. Structures present in
      the higher-molecular-weight fractions (fraction 4 and fraction 5) suggested the
      presence of heteroatoms, dicarboxyl and dihydroxy groups, and organic acid
      compounds with the potential to function as estrogens. Because organic acid
      compositions become dominated by more recalcitrant, higher-molecular-weight acids
      during natural degradation, these findings are important in the context of oil
      sands tailings pond water remediation.

PMID- 25615407
TI  - Identification of variants in the 4q35 gene FAT1 in patients with a
      facioscapulohumeral dystrophy-like phenotype.
AB  - Facioscapulohumeralmuscular dystrophy (FSHD) is linked to copy-number reduction
      (N < 10) of the 4q D4Z4 subtelomeric array, in association with DUX4-permissive
      haplotypes. This main form is indicated as FSHD1. FSHD-like phenotypes may also
      appear in the absence of D4Z4 copy-number reduction. Variants of the SMCHD1 gene
      have been reported to associate with D4Z4 hypomethylation in DUX4-compatible
      haplotypes, thus defining FSHD2. Recently, mice carrying a muscle-specific knock
      out of the protocadherin gene Fat1 or its constitutive hypomorphic allele were
      shown to develop muscular and nonmuscular defects mimicking human FSHD. Here, we
      report FAT1 variants in a group of patients presenting with neuromuscular
      symptoms reminiscent of FSHD. The patients do not carry D4Z4 copy-number
      reduction, 4q hypomethylation, or SMCHD1 variants. However, abnormal splicing of
      the FAT1 transcript is predicted for all identified variants. To determine their
      pathogenicity, we elaborated a minigene approach coupled to an antisense
      oligonucleotide (AON) assay. In vitro, four out of five selected variants induced
      partial or complete alteration of splicing by creating new splice sites or
      modifying splicing regulators. AONs confirmed these effects. Altered transcripts
      may affect FAT1 protein interactions or stability. Altogether, our data suggest
      that defective FAT1 is associated with an FSHD-like phenotype.

PMID- 25615408
TI  - Nutritional aspects of gluten-free products.
AB  - In recent years, gluten-free (GF) goods have become popular, fuelling a growing
      market, as they not only cater to individuals with medical needs but also to
      consumers who seek a GF diet. In their development, it is pivotal to pay
      attention to nutritional quality. This review aims to provide some insights on
      the nutritional quality of GF products, focusing on major concerns and the
      strategies to overcome them. In order to mimic the viscoelastic properties of
      gluten, a large number of flours and starches and other ingredients have been
      used. Therefore the different mixtures of these ingredients bring a wide
      difference in the nutritional composition of GF foods with respect to gluten
      containing counterparts. Several GF foodstuffs contain more fat, including
      saturated, and salt but fewer minerals and vitamins than their equivalents with
      gluten. The increased fibre content and improved technological processes have
      positively affected the glycaemic responses from these goods. However, in order
      to improve their nutritional quality, wholemeal GF cereals and pseudocereals with
      high nutritive value should replace the low-nutritional GF flours and
      consequently the technological processes would be optimized. The improvement of
      the nutritional quality of GF products, and in turn that of the GF diet, should
      also be aimed at lowering the risk of later chronic degenerative disorders,
      especially for infants and young children.

PMID- 25615409
TI  - Plant phosphorus acquisition in a common mycorrhizal network: regulation of
      phosphate transporter genes of the Pht1 family in sorghum and flax.
AB  - In a preceding microcosm study, we found huge differences in phosphorus (P)
      acquisition in sorghum (Sorghum bicolor) and flax (Linum usitatissimum) sharing a
      common mycorrhizal network (CMN). Is the transcriptional regulation of arbuscular
      mycorrhizal (AM)-induced inorganic orthophosphate (Pi) transporters responsible
      for these differences? We characterized and analyzed the expression of Pi
      transporters of the Pht1 family in both plant species, and identified two new AM
      inducible Pi transporters in flax. Mycorrhizal Pi acquisition was strongly
      affected by the combination of plant and AM fungal species. A corresponding
      change in the expression of two AM-inducible Pht1 transporters was noticed in
      both plants (SbPT9, SbPT10, LuPT5 and LuPT8), but the effect was very weak.
      Overall, the expression level of these genes did not explain why flax took up
      more Pi from the CMN than did sorghum. The post-transcriptional regulation of the
      transporters and their biochemical properties may be more important for their
      function than the fine-tuning of their gene expression. 

PMID- 25615410
TI  - Probing phase transitions in simvastatin with terahertz time-domain spectroscopy.
AB  - Simvastatin is known to exist in at least three polymorphic forms. The nature of
      polymorphism in simvastatin is ambiguous, as the crystal structures of the
      polymorphs do not show any significant change in crystal packing or molecular
      conformation. We utilize terahertz time-domain spectroscopy to characterize each
      of the polymorphs and probe the phase transitions in the range of 0.2-3.0 THz and
      for temperatures ranging from 90 to 390 K. In form III, vibrational modes are
      observed at 1.0, 1.25, and 1.7 THz. For form I, we find that the spectrum is
      dominated by a baseline corresponding to libration-vibration motions coupled to
      the dielectric relaxations, which is characteristic of a disordered hydrogen
      bonding material but with additional broad vibrational modes at 0.8 and 1.4 THz.
      In addition, the baseline shifts with temperature similar to that observed in
      disordered materials. This background absorption exhibits pronounced changes
      around the phase transition temperatures at 232 and 272 K. The results are in
      agreement with molecular dynamics simulations, which indicate that changes in the
      rotational freedom of the ester tail in the molecule govern the polymorphism in
      simvastatin. 

PMID- 25615411
TI  - Granule mobility, fusion frequency and insulin secretion are differentially
      affected by insulinotropic stimuli.
AB  - The pre-exocytotic behavior of insulin granules was studied against the
      background of the entirety of submembrane granules in MIN6 cells, and the
      characteristics were compared with the macroscopic secretion pattern and the
      cytosolic Ca(2+) concentration of MIN6 pseudo-islets at 22 degrees C, 32 degrees
      C and 37 degrees C. The mobility of granules labeled by insulin-EGFP and the
      fusion events were assessed by TIRF microscopy utilizing an observer-independent
      algorithm. In the z-dimension, 40 mm K(+) or 30 mm glucose increased the granule
      turnover. The effect of high K(+) was quickly reversible. The increase by glucose
      was more sustained and modified the efficacy of a subsequent K(+) stimulus. The
      effect size of glucose increased with physiological temperature whereas that of
      high K(+) did not. The mobility in the x/y-dimension and the fusion rates were
      little affected by the stimuli, in contrast to secretion. Fusion and secretion,
      however, had the same temperature dependence. Granules that appeared and fused
      within one image sequence had significantly larger caging diameters than pre
      existent granules that underwent fusion. These in turn had a different mobility
      than residence-matched non-fusing granules. In conclusion, delivery to the
      membrane, tethering and fusion of granules are differently affected by
      insulinotropic stimuli. Fusion rates and secretion do not appear to be tightly
      coupled. 

PMID- 25615412
TI  - Human tNASP promotes in vitro nucleosome assembly with histone H3.3.
AB  - Nuclear autoantigenic sperm proteins (NASPs) are members of the acidic histone
      chaperones, which promote nucleosome assembly. In humans, two splicing variants
      proposed for the somatic and testicular isoforms, sNASP and tNASP, respectively,
      have been found, and the shorter form, sNASP, reportedly promotes nucleosome
      assembly with the histone H3 isoforms, H3.1, H3.2, and H3.3. However, the
      biochemical properties of the longer form, tNASP, have not been reported. tNASP
      is considered to exist specifically in the testis. Our present results revealed
      that the tNASP protein is ubiquitously produced in various human tissues, in
      addition to testis. Unexpectedly, we found that the nucleosome assembly activity
      of purified tNASP was extremely low with the canonical histone H3.1 or H3.2, but
      was substantially detected with the replacement histone H3.3 variant. A
      mutational analysis revealed that the H3.3 Ile89 residue, corresponding to the
      H3.1 Val89 residue, is responsible for the tNASP-mediated nucleosome assembly
      with H3.3. A histone deposition assay showed that the H3.3-H4 complex is more
      efficiently deposited onto DNA by tNASP than the H3.1-H4 complex. These results
      provide evidence that tNASP is ubiquitously produced in various types of human
      tissues and promotes in vitro nucleosome assembly with H3 variant specificity. 

PMID- 25615413
TI  - Dual effects of the non-esterified fatty acid receptor 'GPR40' for human health.
AB  - G protein-coupled receptor 40 (GPR40), a receptor for diverse non-esterified
      fatty acids, is expressed predominantly in the wide variety of neurons of the
      central nervous system and beta-cells in the pancreatic islets. Since
      deorphanization of GPR40 in 2003, the past decade has seen major advances in our
      understanding of its role in the insulin secretion. However, there is still a
      great deal to be elucidated about the role of GPR40 in the brain, because the
      latter shows the most abundant GPR40 mRNA expression among the human tissues.
      Since a substantial expression of GPR40 is also seen in the hypothalamus, 'brain
      lipid sensing' might be involved in the control of insulin secretion and energy
      balance. The preceding experiments using monkeys after transient global brain
      ischemia, have highlighted implication of GPR40 for amplifying adult hippocampal
      neurogenesis. Although GPR40-mediated intracellular signaling was recently found
      to result in phosphorylation of cAMP response element-binding protein (CREB)
      necessary for the neuronal differentiation and synaptic plasticity, the signaling
      cascade is still incompletely understood. Furthermore, in response to conjugated
      linoleic acids or trans isomers of arachidonic acid, GPR40 was recently
      demonstrated in rodents to mediate lipotoxicity to beta-cells, neurons, or
      microvessels, which result in diabetes, retinopathy, stroke, etc. However, it
      still remains undetermined in humans whether and how oxidized, conjugated, or
      excessive fatty acids evoke lipotoxicity. Although literature about GPR40 is
      limited especially about the brain or the brain-pancreas interaction, this review
      aims at summarizing beneficial as well as detrimental effects of this receptor in
      the brain and pancreas in response to diverse fatty acids. 

PMID- 25615414
TI  - Gender- and disease-specific urinary thioredoxin in chronic kidney disease
      patients with or without type 2 diabetic nephropathy.
AB  - AIM: The role of urinary (U-) thioredoxin (Trx), a class of small redox proteins,
      in physiological and pathological conditions, in addition to its gender
      specificity, has been insufficiently determined in chronic kidney disease (CKD)
      patients, especially in diabetes mellitus (DM) nephropathy. METHODS: U-Trx was
      measured cross-sectionally in 110 CKD outpatients with estimated glomerular
      filtration rate (eGFR) of >15 mL/min per 1.73 m(2) , namely, in 57 type 2 DM
      patients (male: n = 41, female: n = 16) and 53 non-DM patients (M: n = 33, F: n =
      20), as well as 30 healthy controls (M: n = 11, F: n = 19). Comparisons were made
      among controls, DM and non-DM, and between M and F, with clinical parameters
      compared in each group. In addition, a comparison between average U-Trx level and
      the changes of renal function during a one-year period was performed. RESULTS: U
      Trx was significantly higher in females than in males in controls (P < 0.05) and
      in non-DM patients (P < 0.05). Multiple regression analysis revealed that urinary
      protein (UP)/creatinine (Cr) ratio, female sex and HbA1c were independent factors
      affecting U-Trx among all subjects (adjusted R(2)  = 0.468). In DM patients, U
      Trx was negatively correlated with eGFR, especially in males, and positively
      correlated with UP/Cr and NAG in both sexes (all P < 0.01), as well as with
      systolic blood pressure in all (P < 0.05). Average U-Trx was positively
      correlated with the rate of annual eGFR decline of male (P < 0.01) but not female
      DM patients. CONCLUSION: U-Trx might have a gender-specific physiological and
      pathological role and be a potent marker of renal damage in DM nephropathy.

PMID- 25615416
TI  - Hydroxamate-based colorimetric assay to assess amide bond formation by
      adenylation domain of nonribosomal peptide synthetases.
AB  - We demonstrated the usefulness of a hydroxamate-based colorimetric assay for
      predicting amide bond formation (through an aminoacyl-AMP intermediate) by the
      adenylation domain of nonribosomal peptide synthetases. By using a typical
      adenylation domain of tyrocidine synthetase (involved in tyrocidine
      biosynthesis), we confirmed the correlation between the absorbance at 490 nm of
      the l-Trp-hydroxamate-Fe(3+) complex and the formation of l-Trp-l-Pro, where l
      Pro was used instead of hydroxylamine. Furthermore, this assay was adapted to the
      adenylation domains of surfactin synthetase (involved in surfactin biosynthesis)
      and bacitracin synthetase (involved in bacitracin biosynthesis). Consequently,
      the formation of various aminoacyl l-Pro formations was observed.

PMID- 25615417
TI  - Multiplex ligation-dependent probe amplification for identification of correctly
      targeted murine embryonic stem cell clones.
AB  - Following locus-specific genome editing of mouse embryonic stem cells (ESCs), the
      identification of correctly targeted clones remains a challenge. We applied
      multiplex ligation-dependent probe amplification (MLPA) to screen for homologous
      recombination-based genomic integration of a knockout construct in which part of
      a gene is deleted. All candidate ESCs thereby identified were subsequently
      validated by conventional methods. Thus, MLPA represents a highly reliable as
      well as cost- and time-efficient alternative to currently applied methods such as
      Southern blotting and polymerase chain reaction (PCR)-based approaches. It is
      also applicable to knockin recombination strategies and compatible with the
      CRISPR/Cas9 system and other genome editing strategies. 

PMID- 25615415
TI  - Site- and allele-specific polycomb dysregulation in T-cell leukaemia.
AB  - T-cell acute lymphoblastic leukaemias (T-ALL) are aggressive malignant
      proliferations characterized by high relapse rates and great genetic
      heterogeneity. TAL1 is amongst the most frequently deregulated oncogenes. Yet,
      over half of the TAL1(+) cases lack TAL1 lesions, suggesting unrecognized
      (epi)genetic deregulation mechanisms. Here we show that TAL1 is normally silenced
      in the T-cell lineage, and that the polycomb H3K27me3-repressive mark is focally
      diminished in TAL1(+) T-ALLs. Sequencing reveals that >20% of monoallelic TAL1(+)
      patients without previously known alterations display microinsertions or RAG1/2
      mediated episomal reintegration in a single site 5' to TAL1. Using 'allelic-ChIP'
      and CrispR assays, we demonstrate that such insertions induce a selective switch
      from H3K27me3 to H3K27ac at the inserted but not the germline allele. We also
      show that, despite a considerable mechanistic diversity, the mode of oncogenic
      TAL1 activation, rather than expression levels, impact on clinical outcome.
      Altogether, these studies establish site-specific epigenetic desilencing as a
      mechanism of oncogenic activation. 

PMID- 25615418
TI  - A national survey of healthcare professionals' views on models of follow-up,
      holistic needs assessment and survivorship care for patients with head and neck
      cancer.
AB  - Patterns of follow-up and survivorship care are changing in response to growing
      numbers of cancer survivors and an increasing recognition that traditional models
      are unsustainable and result in unmet needs. Clinicians have shown reluctance in
      changing conventional follow-up practices for patients with head and neck cancer.
      This study aimed to explore nurses' and allied health professionals' views and
      practices in relation to follow-up, holistic needs assessment and survivorship
      care in this patient group. An online survey of members of the British
      Association of Head and Neck Oncology Nurses was undertaken. The response rate
      was 43% (74 of 174). Findings revealed a range of existing models of follow-up,
      rehabilitation and support for people with head and neck cancer across the UK.
      Specialist staff were open to new models of care and to more responsibility, with
      adequate training and supervision. There were some gaps in the provision of
      comprehensive survivorship care and some specific areas of practice in which
      nurses lacked confidence, knowledge and skills, such as managing medications and
      complex symptoms. Further research is needed to develop and evaluate effective
      models of follow-up and support for a growing population of head and neck cancer
      survivors who have diverse and complex needs. 

PMID- 25615419
TI  - Broad phenotypic variability in patients with complex I deficiency due to
      mutations in NDUFS1 and NDUFV1.
AB  - We report clinical, metabolic, genetic and neuroradiological findings in five
      patients from three different families with isolated complex I deficiency.
      Genetic analysis revealed mutations in NDUFS1 in three patients and in NDUFV1 in
      two patients. Four of the mutations are novel and affect amino acid residues that
      either are invariant among species or conserved in their properties. The
      presented clinical courses are characterized by leukoencephalopathy or early
      death and expand the already heterogeneous phenotypic spectrum. A literature
      review was performed, showing that patients with mutations in NDUFS1 in general
      have a worse prognosis than patients with mutations in NDUFV1. 

PMID- 25615420
TI  - Maternally inherited diabetes is associated with a homoplasmic T10003C mutation
      in the mitochondrial tRNA(Gly) gene.
AB  - In this report, we investigate molecular pathogenic mechanism of a diabetes
      associated homoplasmic mitochondrial tRNA mutation in a Han Chinese family with
      maternally transmitted diabetes mellitus. Of 10 adult matrilineal relatives, 5
      individuals suffered from diabetes (4 subjects with only diabetes, one subject
      with both diabetes and hearing impairment), while other five matrilineal
      relatives (one with hearing loss) had glucose intolerance. The average age at
      onset of diabetes in matrilineal relatives was 50 years. Molecular analysis of
      their mitochondrial genomes identified the novel homoplasmic T10003C mutation in
      the tRNA(Gly) gene belonging to haplogroup M11b. The T10003C mutation is expected
      to form a base-pairing (13C-22G) at the highly conserved D-stem of tRNA(Gly),
      thereby affecting secondary structure and function of this tRNA. A tRNA Northern
      analysis revealed that the T10003C mutation caused ~70% reduction in the steady
      state level of tRNA(Gly). An in vivo translation analysis showed ~33% reduction
      in the rate of mitochondrial translation in mutant cells. Oxygen consumption
      analysis showed the defects in overall respiratory capacity or the ATP-linked,
      proton leak, and maximal respiration in mutant cells. As a result, the cellular
      energy deficiency contributes to the development of diabetes in subjects carrying
      the T10003C mutation. These data provide the first direct evidence that the
      tRNA(Gly) mutation might be associated with diabetes. Thus, our findings may
      provide new insights into the understanding of pathophysiology of maternally
      inherited diabetes.

PMID- 25615421
TI  - Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis
      associated bladder cancer.
AB  - An estrogen-DNA adduct mediated pathway may be involved in the pathogenesis of
      the squamous cell carcinoma of the bladder associated with infection with the
      blood fluke Schistosoma haematobium. Extracts from developmental stages of S.
      haematobium, including eggs, induce tumor-like phenotypes in cultured cells. In
      addition, estrogen-derived, reactive metabolites occur in this pathogen and in
      sera of infected persons. Liquid chromatography-mass spectrometry analysis was
      performed on urine from 40 Angolans diagnosed with urogenital schistosomiasis
      (UGS), half of who also presented UGS-associated squamous cell carcinoma and/or
      urothelial cell carcinoma. The analysis revealed numerous estrogen-like
      metabolites, including seven specifically identified in UGS cases, but not
      reported in the database of metabolites in urine of healthy humans. These
      schistosome infection-associated metabolites included catechol estrogen quinones
      (CEQ) and CEQ-DNA-adducts, two of which had been identified previously in S.
      haematobium. In addition, novel metabolites derived directly from 8-oxo-7, 8
      dihydro-2'-deoxyguanosine (8-oxodG) were identified in urine of all 40 cases of
      UGS. These metabolites can be expected to provide deeper insights into the
      carcinogenesis UGS-induced bladder cancer, and as biomarkers for diagnosis and/or
      prognosis of this neglected tropical disease-linked cancer. 

PMID- 25615422
TI  - MLN4924, a novel protein neddylation inhibitor, suppresses proliferation and
      migration of human urothelial carcinoma: In vitro and in vivo studies.
AB  - MLN4924, a small molecule inhibitor of NEDD8 activating enzyme (NAE), has been
      reported to elicit an anti-tumor effect on various malignancies. In this study,
      we investigated the anti-tumor effect of MLN4924 in human urothelial carcinoma
      (UC) in vitro and in vivo by using three human UC cell lines of various grading
      (T24, NTUB1 and RT4). The impact of MLN4924 on UC cells was determined by
      measuring viability (MTT), proliferation (BrdU incorporation), cell cycle
      progression (flow cytometry with propidium iodide staining) and apoptosis (flow
      cytometry with annexin V-FITC labeling). The cell cycle regulatory molecules,
      apoptosis-related molecules, and cell stress-related proteins were examined by
      Western blotting. The influence of tumor cell migration and invasion was analyzed
      by Transwell and wound healing assays. We also evaluated the effects of MLN4924
      on tumor growth by a SCID xenograft mouse model. The data show that MLN4924
      induced dose-dependent cytotoxicity, anti-proliferation, anti-migration, anti
      invasion and apoptosis in human UC cells, accompanied by activations of Bad,
      phospho-histone H2A.X, caspase-3, 7 and PARP, decreased level of phospho-Bcl2,
      and caused cell cycle retardation at the G2M phase. Moreover, MLN4924 activated
      endoplasmic reticulum stress-related molecules (caspase-4, phospho-eIF2alpha, ATF
      4 and CHOP) and other stress responses (JNK and c-Jun activations). Finally, we
      confirmed MLN4924 inhibited tumor growth in a UC xenograft mouse model with
      minimal general toxicity. We concluded that MLN4924 induces apoptosis and cell
      cycle arrest, as well as activation of cell stress responses in human UC. These
      findings imply MLN4924 provides a novel strategy for the treatment of UC. 

PMID- 25615423
TI  - Axonal transport cargo motor count versus average transport velocity: is fast
      versus slow transport really single versus multiple motor transport?
AB  - Cargos have been observed exhibiting a "stop-and-go" behavior (i.e. cargo
      "pause"), and it has generally been assumed that these multi-second pauses can be
      attributed to equally long pauses of cargo-bound motors during motor procession.
      We contend that a careful examination of the isolated microtubule experimental
      record does not support motor pauses. Rather, we believe that the data suggests
      that motor cargo complexes encounter an obstruction that prevents procession,
      eventually detach and reattach, with this obstructed-detach-reattach sequence
      being observed in axon as a "pause." Based on this, along with our quantitative
      evidence-based contention that slow and fast axonal transport are actually single
      and multi-motor transport, we have developed a cargo level motor model capable of
      exhibiting the full range of slow to fast transport solely by changing the number
      of motors involved. This computational model derived using first-order kinetics
      is suitable for both kinesin and dynein and includes load-dependence as well as
      provision for motors encountering obstacles to procession. The model makes the
      following specific predictions: average distance from binding to obstruction is
      about 10 MUm; average motor maximum velocity is at least 6 MUm/s in axon; a
      minimum of 10 motors is required for the fastest fast transport while only one
      motor is required for slow transport; individual in-vivo cargo-attached motors
      may spend as little as 5% of their time processing along a microtubule with the
      remainder being spent either obstructed or unbound to a microtubule; and at least
      in the case of neurofilament transport, kinesin and dynein are largely not being
      in a "tug-of-war" competition.

PMID- 25615424
TI  - Cytoprotective and genoprotective effects of beta-glucans against aflatoxin B1
      induced DNA damage in broiler chicken lymphocytes.
AB  - The polysaccharide beta-glucan presents beneficial effects on the immune system,
      although the mechanisms of the immunomodulatory effect remain poorly understood.
      The potential cytoprotective and genoprotective effects of beta-glucans were
      evaluated in broiler chicken lymphocytes exposed to increasing concentrations of
      aflatoxin B1 (AFB1) and/or beta-glucans. AFB1 significantly decreased cell
      viability at the concentrations of 10 and 20 MUg/ml at 72 h of incubation (p<0.01
      and p<0.001, respectively). Moreover, the AFB1 concentrations of 1, 10 and 20
      MUg/ml increased DNA fragmentation levels at 24 h (p<0.001). Conversely,
      lymphocyte death was prevented by beta-glucans at the concentrations of 1% and
      10%, indicating a cytoprotective effect. Reactive oxygen species levels were
      increased in the cells treated with 20 MUg/ml AFB1 at 24 h (p<0.05) and 10% beta
      glucans with or without AFB1 at 24, 48 and 72 h of incubation (p<0.001). DNA
      damage increased by more than 100% in AFB1-treated lymphocytes when compared to
      control group. beta-glucans at 1% was able to fully revert the AFB1-induced
      lymphocyte DNA damage, indicating a genoprotective effect and maintaining DNA
      integrity. In conclusion, beta-glucans showed in vitro dose-dependent
      cytoprotective and genoprotective effects in broiler chicken lymphocytes exposed
      to AFB1.

PMID- 25615425
TI  - Social comparisons on social media: the impact of Facebook on young women's body
      image concerns and mood.
AB  - The present study experimentally investigated the effect of Facebook usage on
      women's mood and body image, whether these effects differ from an online fashion
      magazine, and whether appearance comparison tendency moderates any of these
      effects. Female participants (N=112) were randomly assigned to spend 10min
      browsing their Facebook account, a magazine website, or an appearance-neutral
      control website before completing state measures of mood, body dissatisfaction,
      and appearance discrepancies (weight-related, and face, hair, and skin-related).
      Participants also completed a trait measure of appearance comparison tendency.
      Participants who spent time on Facebook reported being in a more negative mood
      than those who spent time on the control website. Furthermore, women high in
      appearance comparison tendency reported more facial, hair, and skin-related
      discrepancies after Facebook exposure than exposure to the control website. Given
      its popularity, more research is needed to better understand the impact that
      Facebook has on appearance concerns. 

PMID- 25615426
TI  - Methanol dehydrogenation by iridium N-heterocyclic carbene complexes.
AB  - A series of homogeneous iridium bis(N-heterocyclic carbene) catalysts are active
      for three transformations involving dehydrogenative methanol activation:
      acceptorless dehydrogenation, transfer hydrogenation, and amine monoalkylation.
      The acceptorless dehydrogenation reaction requires base, yielding formate and
      carbonate, as well as 2-3 equivalents of H2. Of the few homogeneous systems known
      for this reaction, our catalysts tolerate air and employ simple ligands. Transfer
      hydrogenation of ketones and imines from methanol is also possible. Finally, N
      monomethylation of anilines occurs through a "borrowing hydrogen" reaction.
      Notably, this reaction is highly selective for the monomethylated product. 

PMID- 25615427
TI  - Phylogenetic relationships of Goneaperca and the evolution of parental care in
      darters (Teleostei: Percidae).
AB  - Inference of evolutionary relationships among closely related darter species
      (Teleostei: Percidae) has traditionally proven challenging due to a lack of
      sufficient numbers of informative morphological characters or reliance on mtDNA
      sequences. These factors have contributed to longstanding uncertainty of the
      monophyly of many described taxonomic groups. Although multi-locus data are now
      available for most darter species, uncertainty has persisted regarding the
      relationships of some major lineages. Here, we investigate the relationships of
      darters classified in Goneaperca, a clade of 46 species, many of which are
      characterized by distinct nuptial displays and male-only parental care. Previous
      phylogenetic analyses of morphological and molecular data have failed to provide
      strong resolution of relationships among major Goneaperca subclades, and
      especially the monophyly of Catonotus. We apply coalescent and phylogenetic
      analyses to a dataset that includes intraspecific sampling for nearly all species
      of Goneaperca for 13 nuclear genes. Our coalescent species tree analyses resolved
      a strongly supported sister relationship between Boleosoma and a monophyletic
      Catonotus. Ancestor state reconstructions using the posterior distribution of
      these newly inferred phylogenies support a single origin of male-only parental
      care in the most recent common ancestor of Boleosoma and Catonotus. 

PMID- 25615428
TI  - The chronology of hand stencils in European Palaeolithic rock art: implications
      of new U-series results from El Castillo Cave (Cantabria, Spain).
AB  - The hand stencils of European Paleolithic art tend to be considered of pre
      Magdalenian age and scholars have generally assigned them to the Gravettian
      period. At El Castillo Cave, application of U-series dating to calcite accretions
      has established a minimum age of 37,290 years for underlying red hand stencils,
      implying execution in the earlier part of the Aurignacian if not beforehand.
      Together with the series of red disks, one of which has a minimum age of 40,800
      years, these motifs lie at the base of the El Castillo parietal stratigraphy. The
      similarity in technique and colour support the notion that both kinds of artistic
      manifestations are synchronic and define an initial, non-figurative phase of
      European cave art. However, available data indicate that hand stencils continued
      to be painted subsequently. Currently, the youngest, reliably dated examples fall
      in the Late Gravettian, approximately 27,000 years ago. 

PMID- 25615429
TI  - Colocalization of nonsegmental vitiligo and extragenital lichen sclerosus in a 45
      year-old female patient with Hashimoto's thyroiditis.

PMID- 25615430
TI  - Effects of coaching on educators' and preschoolers' use of references to print
      and phonological awareness during a small-group craft/writing activity.
AB  - PURPOSE: The current study investigated the effects of coaching as part of an
      emergent literacy professional development program to increase early childhood
      educators' use of verbal references to print and phonological awareness during
      interactions with children. METHOD: Thirty-one educators and 4 children from each
      of their classrooms (N = 121) were randomly assigned to an experimental group (21
      hr of in-service workshops plus 5 coaching sessions) and a comparison group
      (workshops alone). The in-service workshops included instruction on how to talk
      about print and phonological awareness during a post-story craft/writing
      activity. All educators were video-recorded during a 15-min craft/writing
      activity with a small group of preschoolers at pretest and posttest. All
      videotapes were transcribed and coded for verbal references to print and
      phonological awareness by the educators and children. RESULTS: Although at
      posttest, there were no significant group differences in the educators' or the
      children's references to print as measured by rate per minute, both the educators
      and the children in the experimental group used a significantly higher rate per
      minute of references to phonological awareness relative to the comparison group.
      CONCLUSION: Professional development that included coaching with a speech
      language pathologist enabled educators and children to engage in more
      phonological awareness talk during this activity.

PMID- 25615312
TI  - Measurement of prompt psi(2S) to J/psi yield ratios in Pb-Pb and p-p collisions
      at sqrt[sNN]=2.76  TeV.
AB  - The ratio between the prompt psi(2S) and J/psi yields, reconstructed via their
      decays into MU+ MU-, is measured in Pb-Pb and p-p collisions at sqrt[sNN]=2.76 
      TeV. The analysis is based on Pb-Pb and p-p data samples collected by CMS at the
      Large Hadron Collider, corresponding to integrated luminosities of 150  MUb(-1)
      and 5.4  pb(-1), respectively. The double ratio of measured yields
      (Npsi(2S)/N(J/psi))(Pb-Pb)/(Npsi(2S)/N(J/psi))(p-p) is computed in three Pb-Pb
      collision centrality bins and two kinematic ranges: one at midrapidity, |y|<1.6,
      covering the transverse momentum range 6.5<pT<30  GeV/c, and the other at forward
      rapidity, 1.6<|y|<2.4, extending to lower pT values, 3<pT<30  GeV/c. The
      centrality-integrated double ratio changes from 0.45+/-0.13(stat)+/-0.07(syst) in
      the first range to 1.67+/-0.34(stat)+/-0.27(syst) in the second. This difference
      is most pronounced in the most central collisions.

PMID- 25615431
TI  - Contribution of new technologies to characterization and prediction of adverse
      effects.
AB  - Identification of the potential hazards of chemicals has traditionally relied on
      studies in laboratory animals where changes in clinical pathology and
      histopathology compared to untreated controls defined an adverse effect. In the
      past decades, increased consistency in the definition of adversity with
      chemically-induced effects in laboratory animals, as well as in the assessment of
      human relevance has been reached. More recently, a paradigm shift in toxicity
      testing has been proposed, mainly driven by concerns over animal welfare but also
      thanks to the development of new methods. Currently, in vitro approaches,
      toxicogenomic technologies and computational tools, are available to provide
      mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects
      observed in laboratory animals. The vision described as Tox21c (Toxicity Testing
      in the 21st century) aims at predicting in vivo toxicity using a bottom-up
      approach, starting with understanding of MOA based on in vitro data to ultimately
      predict adverse effects in humans. At present, a practical application of the
      Tox21c vision is still far away. While moving towards toxicity prediction based
      on in vitro data, a stepwise reduction of in vivo testing is foreseen by
      combining in vitro with in vivo tests. Furthermore, newly developed methods will
      also be increasingly applied, in conjunction with established methods in order to
      gain trust in these new methods. This confidence is based on a critical
      scientific prerequisite: the establishment of a causal link between data obtained
      with new technologies and adverse effects manifested in repeated-dose in vivo
      toxicity studies. It is proposed to apply the principles described in the
      WHO/IPCS framework of MOA to obtain this link. Finally, an international database
      of known MOAs obtained in laboratory animals using data-rich chemicals will
      facilitate regulatory acceptance and could further help in the validation of the
      toxicity pathway and adverse outcome pathway concepts.

PMID- 25615434
TI  - Evaluation of a problem-solving (PS) techniques-based intervention for informal
      carers of patients with dementia receiving in-home care.
AB  - BACKGROUND: The value of care provided by informal carers in Canada is estimated
      at $26 billion annually (Hollander et al., 2009). However, carers' needs are
      often overlooked, limiting their capacity to provide care. Problem-solving
      therapy (PST), a structured approach to problem solving (PS) and a core principle
      of the Reitman Centre CARERS Program, has been shown to alleviate emotional
      distress and improve carers' competence (Chiu et al., 2013). This study evaluated
      the effectiveness of problem-solving techniques-based intervention based on
      adapted PST methods, in enhancing carers' physical and emotional capacity to care
      for relatives with dementia living in the community. METHODS: 56 carers were
      equally allocated to a problem-solving techniques-based intervention group or a
      control arm. Carers in the intervention group received three 1 hr visits by a
      care coordinator (CC) who had been given advanced training in PS techniques-based
      intervention. Coping, mastery, competence, burden, and perceived stress of the
      carers were evaluated at baseline and post-intervention using standardized
      assessment tools. An intention-to-treat analysis utilizing repeated measures
      ANOVA was performed on the data. RESULTS: Post-intervention measures completion
      rate was 82% and 92% for the intervention and control groups, respectively.
      Carers in the intervention group showed significantly improved task-oriented
      coping, mastery, and competence and significantly reduced emotion-oriented
      coping, burden and stress (p < 0.01-0.001). Control carers showed no change.
      CONCLUSION: PS techniques, when learned and delivered by CCs as a tool to coach
      carers in their day-to-day caregiving, improves carers' caregiving competence,
      coping, burden, and perceived stress. This may reduce dependence on primary,
      psychiatric, and institutional care. Results provide evidence that establishing
      effective partnerships between inter-professional clinicians in academic clinical
      health science centers, and community agencies can extend the reach of the
      expertise of specialized health care institutions.

PMID- 25615433
TI  - Phenotypic heterogeneity of hemostasis in severe hemophilia.
AB  - A reduction in bleeding pattern and arthropathy appears to be observed in
      approximately 10% of the patients with severe hemophilia (< 1% clotting factor
      activity). These patients rarely bleed and do not always need prophylactic
      therapy of therapeutic products, resulting in the wide range of joint damage seen
      in patients with severe hemophilia. The cause(s) of this phenotypic heterogeneity
      has been investigated in many studies till date, but remains to be completely
      solved. The large heterogeneity of the clinical phenotype in severe hemophilia
      seems to be multifactorial, including variation in the levels of various
      procoagulant and anticoagulant factors, the balance between the coagulation and
      fibrinolysis systems, pharmacokinetics of therapeutic products, environmental
      factors including lifestyle activity, and the limitation of measurement at lower
      levels of clotting factors. As an approach toward clarification, studies should
      be designed to evaluate a homogenous cohort of hemophilic A patients with an
      intron 22 inversion who produce no factor VIII. In the future, by a combination
      of the measurement of lower levels of clotting factors and the evaluation of
      global clotting function, it might be possible to better grasp the potential of
      hemostatic coagulation in individual hemophilia patients, which should in turn be
      useful for the prediction of bleeding phenotype and the designation of adequate
      and long-term hemostatic management throughout their life. 

PMID- 25615432
TI  - Factor XIII deficiency in Iran: a comprehensive review of the literature.
AB  - Factor XIII deficiency (FXIIID) is a rare bleeding disorder with an estimated
      prevalence of 1 in 2-million population worldwide. In Iran, a Middle Eastern
      country with a high rate of consanguineous marriages, there are approximately 473
      patients afflicted with FXIIID. An approximately 12-fold higher prevalence of
      FXIIID is estimated in Iran in comparison with overall worldwide frequency. In
      this study, we have undertaken a comprehensive review on different aspects of
      FXIIID in the Iranian population. The distribution of this disease in different
      regions of Iran reveals that Sistan and Baluchestan Province has not only the
      highest number of patients with FXIIID in Iran but the highest global incidence
      of this condition. Among Iranian patients, umbilical cord bleeding, hematoma, and
      prolonged wound bleeding are the most frequent clinical manifestations. There are
      several disease causing mutations in Iranian patients with FXIIID, with Trp187Arg
      being the most common mutation in FXIIID in Iran. Traditionally, the management
      of FXIIID in Iran was only based on administration of fresh frozen plasma or
      cryoprecipitate, until 2009 when FXIII concentrate became available for patient
      management. Various studies have evaluated the efficacy and safety of
      prophylactic regimens in different situations with valuable findings. Although
      the focus of this study is on Iran, it offers considerable insight into FXIIID,
      which can be applied more extensively to improve the management and quality of
      life in all affected patients. 

PMID- 25615435
TI  - Microbial dark matter ecogenomics reveals complex synergistic networks in a
      methanogenic bioreactor.
AB  - Ecogenomic investigation of a methanogenic bioreactor degrading terephthalate
      (TA) allowed elucidation of complex synergistic networks of uncultivated
      microorganisms, including those from candidate phyla with no cultivated
      representatives. Our previous metagenomic investigation proposed that
      Pelotomaculum and methanogens may interact with uncultivated organisms to degrade
      TA; however, many members of the community remained unaddressed because of past
      technological limitations. In further pursuit, this study employed state-of-the
      art omics tools to generate draft genomes and transcriptomes for uncultivated
      organisms spanning 15 phyla and reports the first genomic insight into candidate
      phyla Atribacteria, Hydrogenedentes and Marinimicrobia in methanogenic
      environments. Metabolic reconstruction revealed that these organisms perform
      fermentative, syntrophic and acetogenic catabolism facilitated by energy
      conservation revolving around H2 metabolism. Several of these organisms could
      degrade TA catabolism by-products (acetate, butyrate and H2) and syntrophically
      support Pelotomaculum. Other taxa could scavenge anabolic products (protein and
      lipids) presumably derived from detrital biomass produced by the TA-degrading
      community. The protein scavengers expressed complementary metabolic pathways
      indicating syntrophic and fermentative step-wise protein degradation through
      amino acids, branched-chain fatty acids and propionate. Thus, the uncultivated
      organisms may interact to form an intricate syntrophy-supported food web with
      Pelotomaculum and methanogens to metabolize catabolic by-products and detritus,
      whereby facilitating holistic TA mineralization to CO2 and CH4. 

PMID- 25615436
TI  - Ecophysiology of uncultivated marine euryarchaea is linked to particulate organic
      matter.
AB  - Particles in aquatic environments host distinct communities of microbes, yet the
      evolution of particle-specialized taxa and the extent to which specialized
      microbial metabolism is associated with particles is largely unexplored. Here, we
      investigate the hypothesis that a widely distributed and uncultivated microbial
      group--the marine group II euryarchaea (MGII)--interacts with living and detrital
      particulate organic matter (POM) in the euphotic zone of the central California
      Current System. Using fluorescent in situ hybridization, we verified the
      association of euryarchaea with POM. We further quantified the abundance and
      distribution of MGII 16 S ribosomal RNA genes in size-fractionated seawater
      samples and compared MGII functional capacity in metagenomes from the same
      fractions. The abundance of MGII in free-living and >3 MUm fractions decreased
      with increasing distance from the coast, whereas MGII abundance in the 0.8-3 MUm
      fraction remained constant. At several offshore sites, MGII abundance was highest
      in particle fractions, indicating that particle-attached MGII can outnumber free
      living MGII under oligotrophic conditions. Compared with free-living MGII, the
      genome content of MGII in particle-associated fractions exhibits an increased
      capacity for surface adhesion, transcriptional regulation and catabolism of high
      molecular weight substrates. Moreover, MGII populations in POM fractions are
      phylogenetically distinct from and more diverse than free-living MGII. Eukaryotic
      phytoplankton additions stimulated MGII growth in bottle incubations, providing
      the first MGII net growth rate measurements. These ranged from 0.47 to 0.54 d(
      1). However, MGII were not recovered in whole-genome amplifications of flow
      sorted picoeukaryotic phytoplankton and heterotrophic nanoflagellates, suggesting
      that MGII in particle fractions are not physically attached to living POM.
      Collectively, our results support a linkage between MGII ecophysiology and POM,
      implying that marine archaea have a role in elemental cycling through
      interactions with particles.

PMID- 25615437
TI  - Methanogenic food web in the gut contents of methane-emitting earthworm Eudrilus
      eugeniae from Brazil.
AB  - The anoxic saccharide-rich conditions of the earthworm gut provide an ideal
      transient habitat for ingested microbes capable of anaerobiosis. It was recently
      discovered that the earthworm Eudrilus eugeniae from Brazil can emit methane
      (CH4) and that ingested methanogens might be associated with this emission. The
      objective of this study was to resolve trophic interactions of bacteria and
      methanogens in the methanogenic food web in the gut contents of E. eugeniae. RNA
      based stable isotope probing of bacterial 16S rRNA as well as mcrA and mrtA (the
      alpha subunit of methyl-CoM reductase and its isoenzyme, respectively) of
      methanogens was performed with [(13)C]-glucose as a model saccharide in the gut
      contents. Concomitant fermentations were augmented by the rapid consumption of
      glucose, yielding numerous products, including molecular hydrogen (H2), carbon
      dioxide (CO2), formate, acetate, ethanol, lactate, succinate and propionate.
      Aeromonadaceae-affiliated facultative aerobes, and obligate anaerobes affiliated
      to Lachnospiraceae, Veillonellaceae and Ruminococcaceae were associated with the
      diverse fermentations. Methanogenesis was ongoing during incubations, and (13)C
      labeling of CH4 verified that supplemental [(13)C]-glucose derived carbon was
      dissimilated to CH4. Hydrogenotrophic methanogens affiliated with
      Methanobacteriaceae and Methanoregulaceae were linked to methanogenesis, and
      acetogens related to Peptostreptoccocaceae were likewise found to be participants
      in the methanogenic food web. H2 rather than acetate stimulated methanogenesis in
      the methanogenic gut content enrichments, and acetogens appeared to dissimilate
      supplemental H2 to acetate in methanogenic enrichments. These findings provide
      insight on the processes and associated taxa potentially linked to methanogenesis
      and the turnover of organic carbon in the alimentary canal of methane-emitting E.
      eugeniae. 

PMID- 25615438
TI  - Quorum sensing-regulated chitin metabolism provides grazing resistance to Vibrio
      cholerae biofilms.
AB  - Association of Vibrio cholerae with chitinous surfaces of zooplankton is
      important for its persistence in marine environments, as it provides
      accessibility to nutrients and resistance to stresses. Predation by heterotrophic
      protists has a major impact on the survival of V. cholerae. V. cholerae forms
      biofilms as its main defensive strategy, and quorum sensing (QS) additionally
      regulates the production of antiprotozoal factors. The role of chitin and QS
      regulation in V. cholerae grazing resistance was investigated by exposing V.
      cholerae wild-type (WT) and QS mutant biofilms grown on chitin flakes to the
      bacteriotrophic, surface-feeding flagellate Rhynchomonas nasuta. V. cholerae
      formed more biofilm biomass on chitin flakes compared with nonchitinous surfaces.
      The growth of R. nasuta was inhibited by WT biofilms grown on chitin flakes,
      whereas the inhibition was attenuated in QS mutant biofilms. The chitin-dependent
      toxicity was also observed when the V. cholerae biofilms were developed under
      continuous flow or grown on a natural chitin source, the exoskeleton of Artemia.
      In addition, the antiprotozoal activity and ammonium concentration of V. cholerae
      biofilm supernatants were quantified. The ammonium levels (3.5 mM) detected in
      the supernatants of V. cholerae WT biofilms grown on chitin flakes were estimated
      to reduce the number of R. nasuta by >80% in add-back experiments, and the
      supernatant of QS mutant biofilms was less toxic owing to a decrease in ammonium
      production. Transcriptomic analysis revealed that the majority of genes involved
      in chitin metabolism and chemotaxis were significantly downregulated in QS mutant
      biofilms when grown on chitin compared with the WT biofilms. 

PMID- 25615439
TI  - Non-social adaptation defers a tragedy of the commons in Pseudomonas aeruginosa
      quorum sensing.
AB  - In a process termed quorum sensing (QS), the opportunistic bacterial pathogen
      Pseudomonas aeruginosa uses diffusible signaling molecules to regulate the
      expression of numerous secreted factors or public goods that are shared within
      the population. But not all cells respond to QS signals. These social cheaters
      typically harbor a mutation in the QS receptor gene lasR and exploit the public
      goods produced by cooperators. Here we show that non-social adaptation under
      growth conditions that require QS-dependent public goods increases tolerance to
      cheating and defers a tragedy of the commons. The underlying mutation is in the
      transcriptional repressor gene psdR. This mutation has no effect on public goods
      expression but instead increases individual fitness by derepressing growth
      limiting intracellular metabolism. Even though psdR mutant populations remain
      susceptible to invasion by isogenic psdR lasR cheaters, they bear a lower cheater
      load than do wild-type populations, and they are completely resistant to invasion
      by lasR cheaters with functional psdR. Mutations in psdR also sustain growth near
      wild-type levels when paired with certain partial loss-of-function lasR
      mutations. Targeted sequencing of multiple evolved isolates revealed that
      mutations in psdR arise before mutations in lasR, and rapidly sweep through the
      population. Our results indicate that a QS-favoring environment can lead to
      adaptations in non-social, intracellular traits that increase the fitness of
      cooperating individuals and thereby contribute to population-wide maintenance of
      QS and associated cooperative behaviors. 

PMID- 25615441
TI  - Gender role attitudes across the transition to adolescent motherhood in Mexican
      origin families.
AB  - Using longitudinal data collected at four time points from 191 dyads of Mexican
      origin adolescent first-time mothers and their mother figures, we examined
      changes in and socialization of traditional gender role attitudes across the
      transition to parenthood using latent growth curve modeling and actor-partner
      interdependence modeling. Longitudinal growth models indicated that, regardless
      of nativity status, adolescent mothers' and their foreign-born mother figures'
      gender role attitudes became more egalitarian across adolescents' transition to
      parenthood, spanning from the 3rd trimester of pregnancy to 36 months postpartum.
      Furthermore, actor-partner interdependence modeling suggested that adolescents'
      and their mother figures' gender role attitudes during adolescents' third
      trimester of pregnancy equally contributed to subsequent increases in one
      another's gender role attitudes at 10 months postpartum. Importantly, this
      reciprocal socialization process was not moderated by adolescent mothers' nor by
      their mother figures' nativity status. Findings suggest that it is important to
      understand the cultural and intergenerational family processes that contribute to
      the development of gender role attitudes during the transition to parenthood for
      adolescent mothers and their mother figures in Mexican-origin families. 

PMID- 25615440
TI  - Chemotaxis by natural populations of coral reef bacteria.
AB  - Corals experience intimate associations with distinct populations of marine
      microorganisms, but the microbial behaviours underpinning these relationships are
      poorly understood. There is evidence that chemotaxis is pivotal to the infection
      process of corals by pathogenic bacteria, but this evidence is limited to
      experiments using cultured isolates under laboratory conditions. We measured the
      chemotactic capabilities of natural populations of coral-associated bacteria
      towards chemicals released by corals and their symbionts, including amino acids,
      carbohydrates, ammonium and dimethylsulfoniopropionate (DMSP). Laboratory
      experiments, using a modified capillary assay, and in situ measurements, using a
      novel microfabricated in situ chemotaxis assay, were employed to quantify the
      chemotactic responses of natural microbial assemblages on the Great Barrier Reef.
      Both approaches showed that bacteria associated with the surface of the coral
      species Pocillopora damicornis and Acropora aspera exhibited significant levels
      of chemotaxis, particularly towards DMSP and amino acids, and that these levels
      of chemotaxis were significantly higher than that of bacteria inhabiting nearby,
      non-coral-associated waters. This pattern was supported by a significantly higher
      abundance of chemotaxis and motility genes in metagenomes within coral-associated
      water types. The phylogenetic composition of the coral-associated chemotactic
      microorganisms, determined using 16S rRNA amplicon pyrosequencing, differed from
      the community in the seawater surrounding the coral and comprised known coral
      associates, including potentially pathogenic Vibrio species. These findings
      indicate that motility and chemotaxis are prevalent phenotypes among coral
      associated bacteria, and we propose that chemotaxis has an important role in the
      establishment and maintenance of specific coral-microbe associations, which may
      ultimately influence the health and stability of the coral holobiont. 

PMID- 25615442
TI  - Spinal cord injury secondary to electrocution in a dog.
AB  - A 13-year-old, female spayed, crossbreed dog of 32 kg was presented for
      evaluation of peracute onset of non-ambulatory tetraparesis after chewing an
      electrical wire. Neurological examination was consistent with a C1-C5 myelopathy.
      Magnetic resonance imaging revealed a focal intramedullary lesion over the C2-C3
      vertebral bodies, which was confirmed to be an acute focal necrotising
      poliomyelopathy with subarachnoid and subdural haemorrhages on postmortem
      examination. This report describes the clinical, imaging and histopathological
      findings of this unusual type of spinal cord injury, and the effects of
      electrocution in the central nervous system of dogs. 

PMID- 25615443
TI  - Towards a new FRET system via combination of pyrene and perylene bisimide:
      synthesis, self-assembly and fluorescence behavior.
AB  - A new fluorescent derivative of cholesterol, N,N'-(N-(2-(3beta-cholest-5-en-3yl
      formamido)ethyl) pyrene-1-sulfonamido)ethyl perylene-3,4:9,10-tetracarboxylic
      acid bisimide (CPPBI), was designed and synthesized. In the design, pyrene (Py)
      and perylene bisimide (PBI) were specially chosen as the energy donor and the
      acceptor, respectively. Fluorescence studies revealed that (1) CPPBI shows a
      strong tendency to form supra-molecular assemblies, (2) the assemblies possess a
      high efficiency of fluorescence resonance energy transfer (FRET) via
      intermolecular interactions, and (3) the profile and position of its fluorescence
      emission are highly dependent upon the nature of its medium, but the medium shows
      little effect on the efficiency of the energy transfer, suggesting that the
      chromophores including both Py and PBI units enjoy some rotational and/or
      translational mobility in the aggregated state of the compound. Temperature- and
      concentration-dependent (1)H NMR spectroscopy studies revealed that both hydrogen
      bonding and pi-pi stacking play a great role in stabilizing the assemblies of the
      compound, and confirmed the existence of pi-pi stacking between the Py moieties
      and between the PBI residues of the compound, of which the donor and the acceptor
      may have arranged in an appropriate orientation and at a suitable distance which
      are the key factors to determine the FRET efficiency. Moreover, the CPPBI-based
      film possesses unusual photochemical stability, and its emission is sensitive to
      the presence of some organic vapors, in particular aniline. 

PMID- 25615444
TI  - Electron pairing in designer materials: a novel strategy for a negative effective
      Hubbard U.
AB  - We propose a set of design rules with a model Hamiltonian that allows electrons
      to form attracting pairs through the exploitation of a new combination of
      resonant band alignment and Coulombic repulsion. The pair bands and single
      particle bands in various lattices are calculated and compared in energy, and
      regions of net attraction are identified. This work provides guidelines for the
      construction of molecular systems, nanocrystals, and nanoparticle arrays with the
      potential for superconductivity. 

PMID- 25615445
TI  - Treatment satisfaction of men and partners following switch from on-demand
      phosphodiesterase type 5 inhibitor therapy to tadalafil 5 mg once daily.
AB  - INTRODUCTION: Treatment satisfaction of men receiving phosphodiesterase 5
      inhibitors (PDE5) for erectile dysfunction (ED) and their partners is essential
      to successful long-term therapy. AIM: This study aims to assess treatment
      satisfaction, in men with a partial response to on-demand (PRN) PDE5 and their
      female partners, following tadalafil 5 mg once daily or placebo. METHODS: The
      study was randomized, double-blind, parallel, and placebo-controlled in men
      primarily with mild to moderate ED. Treatment satisfaction was assessed following
      a 4-week maximum dose PRN lead-in, 4-week nondrug washout, and treatment through
      12 weeks. Men were >=18 years old with ED for >=3 months and International Index
      of Erectile Function Erectile Function score of >=17 and <26 at screening and <26
      following PRN lead-in. MAIN OUTCOME MEASURES: Treatment satisfaction was assessed
      using the Treatment Satisfaction Scale (TSS) for patients and partners. TSS
      domain scores range from 0 to 100, with higher values indicating greater
      satisfaction. Statistical comparisons were made using analysis of covariance.
      RESULTS: Treatment satisfaction was significantly greater with tadalafil once
      daily vs. placebo across all TSS domains for both patients and their partners
      (all P < 0.001). For patients, mean scores for the TSS domains Confidence to
      Complete Sexual Activity and Satisfaction with Orgasm ranged from 53.7 to 57.8
      after the PRN lead-in and 26.7 to 31.9 following the nondrug washout. Following
      randomized treatment, scores for tadalafil and placebo were 55.4 and 32.6,
      respectively, for Confidence to Complete Sexual Activity and 57.5 and 37.9,
      respectively, for Satisfaction with Orgasm. Results were comparable for other TSS
      domains and between men and their partners. CONCLUSIONS: Treatment satisfaction
      was comparable for tadalafil 5 mg once daily and PRN PDE5 for both patients and
      female partners, suggesting that tadalafil once daily is a viable therapy option
      for men with ED who had a partial response to PRN PDE5 therapy.

PMID- 25615446
TI  - Pyrosequencing revealed SAR116 clade as dominant dddP-containing bacteria in
      oligotrophic NW Pacific Ocean.
AB  - Dimethyl sulfide (DMS) is a climatically active gas released into the atmosphere
      from oceans. It is produced mainly by bacterial enzymatic cleavage of
      dimethylsulfoniopropionate (DMSP), and six DMSP lyases have been identified to
      date. To determine the biogeographical distribution of bacteria relevant to DMS
      production, we investigated the diversity of dddP-the most abundant DMS-producing
      gene-in the northwestern Pacific Ocean using newly developed primers and the
      pyrosequencing method. Consistent with previous studies, the major dddP
      containing bacteria in coastal areas were those belonging to the Roseobacter
      clade. However, genotypes closely related to the SAR116 group were found to
      represent a large portion of dddP-containing bacteria in the surface waters of
      the oligotrophic ocean. The addition of DMSP to a culture of the SAR116 strain
      Candidatus Puniceispirillum marinum IMCC1322 resulted in the production of DMS
      and upregulated expression of the dddP gene. Considering the large area of
      oligotrophic water and the wide distribution of the SAR116 group in oceans
      worldwide, we propose that these bacteria may play an important role in oceanic
      DMS production and biogeochemical sulfur cycles, especially via bacteria-mediated
      DMSP degradation.

PMID- 25615447
TI  - Dangerous driving in a Chinese sample: associations with morningness-eveningness
      preference and personality.
AB  - Individual differences in morningness-eveningness preference may influence
      susceptibility and response to sleepiness. These differences could influence
      driving performance, but the influence of morningness-eveningness preference on
      driving behavior and accident risk has not been comprehensively studied. As
      morningness-eveningness preference is associated with personality
      characteristics, we also investigated how the interaction between morningness
      eveningness preference and personality may be related to dangerous driving
      behaviors. Two hundred and ninety five drivers completed the reduced Morningness
      Eveningness Questionnaire, the Dula Dangerous Driving Index, and personality
      scales for agreeableness, conscientiousness and neuroticism, and reported
      demographic information (gender, age, level of education, driving years and
      annual average driving mileage) and self-reported traffic violations (accidents,
      penalty points and fines). The results showed that more Risky Driving, Aggressive
      Driving, Negative Cognitive/Emotional Driving and Drunk Driving, as measured by
      the Dula Dangerous Driving Index, were all significantly correlated with more
      eveningness, corresponding to lower scores on the reduced Morningness-Eveningness
      Questionnaire. Moreover, eveningness was correlated with self-reported traffic
      accidents, penalty points and fines. Furthermore, a moderation effect was found:
      eveningness was more strongly associated with risky driving and negative
      emotional driving in those who scored high for trait agreeableness. 

PMID- 25615448
TI  - Clonal analysis of meningococci during a 26 year period prior to the introduction
      of meningococcal serogroup C vaccines.
AB  - Meningococcal disease remains a public health burden in the UK and elsewhere.
      Invasive Neisseria meningitidis, isolated in Scotland between 1972 and 1998, were
      characterised retrospectively to examine the serogroup and clonal structure of
      the circulating population. 2607 isolates causing invasive disease were available
      for serogroup and MLST analysis whilst 2517 were available for multilocus
      sequence typing (MLST) analysis only. Serogroup distribution changed from year to
      year but serogroups B and C were dominant throughout. Serogroup B was dominant
      throughout the 1970s and early 1980s until serogroup C became dominant during the
      mid-1980s. The increase in serogroup C was not associated with one particular
      sequence type (ST) but was associated with a number of STs, including ST-8, ST
      11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease
      seen in the 1990s that was due to expansion of the ST-11 clonal complex. While
      there was considerable diversity among the isolates (309 different STs among the
      2607 isolates), a large proportion of isolates (59.9%) were associated with only
      10 STs. These data highlight meningococcal diversity over time and the need for
      ongoing surveillance during the introduction of new meningococcal vaccines. 

PMID- 25615451
TI  - Regioselective oxidative trifluoromethylation of imidazoheterocycles via C(sp2)-H
      bond functionalization.
AB  - Catalytic oxidative trifluoromethylation of imidazopyridines has been carried out
      at room temperature through the functionalization of the sp(2) C-H bond employing
      Langlois reagent under ambient air. A library of 3-(trifluoromethyl)imidazo[1,2
      a]pyridines with broad functionalities have been synthesized regioselectively.
      This methodology is also applicable to imidazo[2,1-b]thiazole and
      benzo[d]imidazo[2,1-b]thiazole. 

PMID- 25615449
TI  - Prediction formulas for individual opioid analgesic requirements based on genetic
      polymorphism analyses.
AB  - BACKGROUND: The analgesic efficacy of opioids is well known to vary widely among
      individuals, and various factors related to individual differences in opioid
      sensitivity have been identified. However, a prediction model to calculate
      appropriate opioid analgesic requirements has not yet been established. The
      present study sought to construct prediction formulas for individual opioid
      analgesic requirements based on genetic polymorphisms and clinical data from
      patients who underwent cosmetic orthognathic surgery and validate the utility of
      the prediction formulas in patients who underwent major open abdominal surgery.
      METHODS: To construct the prediction formulas, we performed multiple linear
      regression analyses using data from subjects who underwent cosmetic orthognathic
      surgery. The dependent variable was 24-h postoperative or perioperative fentanyl
      use, and the independent variables were age, gender, height, weight, pain
      perception latencies (PPL), and genotype data of five single-nucleotide
      polymorphisms (SNPs). To examine the utility of the prediction formulas, we
      performed simple linear regression analyses using subjects who underwent major
      open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use
      and the predicted values that were calculated using the multiple regression
      equations were incorporated as dependent and independent variables, respectively.
      RESULTS: Multiple linear regression analyses showed that the four SNPs, PPL, and
      weight were retained as independent predictors of 24-h postoperative fentanyl use
      (R2 = 0.145, P = 5.66 * 10-10) and the two SNPs and weight were retained as
      independent predictors of perioperative fentanyl use (R2 = 0.185, P = 1.99 * 10
      15). Simple linear regression analyses showed that the predicted values were
      retained as an independent predictor of actual 24-h postoperative analgesic use
      (R2 = 0.033, P = 0.030) and perioperative analgesic use (R2 = 0.100, P = 1.09 *
      10-4), respectively. CONCLUSIONS: We constructed prediction formulas, and the
      possible utility of these prediction formulas was found in another type of
      surgery.

PMID- 25615450
TI  - Human mitochondrial Hsp70 (mortalin): shedding light on ATPase activity,
      interaction with adenosine nucleotides, solution structure and domain
      organization.
AB  - The human mitochondrial Hsp70, also called mortalin, is of considerable
      importance for mitochondria biogenesis and the correct functioning of the cell
      machinery. In the mitochondrial matrix, mortalin acts in the importing and
      folding process of nucleus-encoded proteins. The in vivo deregulation of mortalin
      expression and/or function has been correlated with age-related diseases and
      certain cancers due to its interaction with the p53 protein. In spite of its
      critical biological roles, structural and functional studies on mortalin are
      limited by its insoluble recombinant production. This study provides the first
      report of the production of folded and soluble recombinant mortalin when co
      expressed with the human Hsp70-escort protein 1, but it is still likely prone to
      self-association. The monomeric fraction of mortalin presented a slightly
      elongated shape and basal ATPase activity that is higher than that of its
      cytoplasmic counterpart Hsp70-1A, suggesting that it was obtained in the
      functional state. Through small angle X-ray scattering, we assessed the low
      resolution structural model of monomeric mortalin that is characterized by an
      elongated shape. This model adequately accommodated high resolution structures of
      Hsp70 domains indicating its quality. We also observed that mortalin interacts
      with adenosine nucleotides with high affinity. Thermally induced unfolding
      experiments indicated that mortalin is formed by at least two domains and that
      the transition is sensitive to the presence of adenosine nucleotides and that
      this process is dependent on the presence of Mg2+ ions. Interestingly, the
      thermal-induced unfolding assays of mortalin suggested the presence of an
      aggregation/association event, which was not observed for human Hsp70-1A, and
      this finding may explain its natural tendency for in vivo aggregation. Our study
      may contribute to the structural understanding of mortalin as well as to
      contribute for its recombinant production for antitumor compound screenings. 

PMID- 25615452
TI  - Sb(V) reactivity with human blood components: redox effects.
AB  - We assessed the reactivity of Sb(V) in human blood. Sb(V) reactivity was
      determined using an HPLC-HG-AFS hyphenated system. Sb(V) was partially reduced to
      Sb(III) in blood incubation experiments; however, Sb(III) was a highly unstable
      species. The addition of 0.1 mol L(-1) EDTA prevented Sb(III) oxidation, thus
      enabling the detection of the reduction of Sb(V) to Sb(III). The transformation
      of Sb(V) to Sb(III) in human whole blood was assessed because the reduction of
      Sb(V) in human blood may likely generate redox side effects. Our results indicate
      that glutathione was the reducing agent in this reaction and that Sb(V)
      significantly decreased the GSH/GSSG ratio from 0.32 +/- 0.09 to 0.07 +/- 0.03.
      Moreover, the presence of 200 ng mL(-1) of Sb(V) increased the activity of
      superoxide dismutase from 4.4 +/- 0.1 to 7.0 +/- 0.4 U mL(-1) and decreased the
      activity of glutathione peroxidase from 62 +/- 1 to 34 +/- 2 nmol min(-1) mL(-1).

PMID- 25615453
TI  - Measuring the biphoton temporal wave function with polarization-dependent and
      time-resolved two-photon interference.
AB  - We propose and demonstrate an approach to measuring the biphoton temporal wave
      function with polarization-dependent and time-resolved two-photon interference.
      Through six sets of two-photon interference measurements projected onto different
      polarization subspaces, we can reconstruct the amplitude and phase functions of
      the biphoton temporal waveform. For the first time, we apply this technique to
      experimentally determine the temporal quantum states of the narrow-band biphotons
      generated from the spontaneous four-wave mixing in cold atoms. 

PMID- 25615454
TI  - Coherence and decay of higher energy levels of a superconducting transmon qubit.
AB  - We present measurements of coherence and successive decay dynamics of higher
      energy levels of a superconducting transmon qubit. By applying consecutive pi
      pulses for each sequential transition frequency, we excite the qubit from the
      ground state up to its fourth excited level and characterize the decay and
      coherence of each state. We find the decay to proceed mainly sequentially, with
      relaxation times in excess of 20  MUs for all transitions. We also provide a
      direct measurement of the charge dispersion of these levels by analyzing beating
      patterns in Ramsey fringes. The results demonstrate the feasibility of using
      higher levels in transmon qubits for encoding quantum information. 

PMID- 25615455
TI  - Experimental observation of Lee-Yang zeros.
AB  - Lee-Yang zeros are points on the complex plane of physical parameters where the
      partition function of a system vanishes and hence the free energy diverges. Lee
      Yang zeros are ubiquitous in many-body systems and fully characterize their
      thermodynamics. Notwithstanding their fundamental importance, Lee-Yang zeros have
      never been observed in experiments, due to the intrinsic difficulty that they
      would occur only at complex values of physical parameters, which are generally
      regarded as unphysical. Here we report the first observation of Lee-Yang zeros,
      by measuring quantum coherence of a probe spin coupled to an Ising-type spin
      bath. The quantum evolution of the probe spin introduces a complex phase factor
      and therefore effectively realizes an imaginary magnetic field. From the measured
      Lee-Yang zeros, we reconstructed the free energy of the spin bath and determined
      its phase transition temperature. This experiment opens up new opportunities of
      studying thermodynamics in the complex plane. 

PMID- 25615456
TI  - General magnetic transition dipole moments for electron paramagnetic resonance.
AB  - We present general expressions for the magnetic transition rates in electron
      paramagnetic resonance (EPR) experiments of anisotropic spin systems in the solid
      state. The expressions apply to general spin centers and arbitrary excitation
      geometry (Voigt, Faraday, and intermediate). They work for linear and circular
      polarized as well as unpolarized excitation, and for crystals and powders. The
      expressions are based on the concept of the (complex) magnetic transition dipole
      moment vector. Using the new theory, we determine the parities of ground and
      excited spin states of high-spin (S=5/2) Fe(III) in hemin from the polarization
      dependence of experimental EPR line intensities.

PMID- 25615457
TI  - Dark matter with pseudoscalar-mediated interactions explains the DAMA signal and
      the galactic center excess.
AB  - We study a Dirac dark matter particle interacting with ordinary matter via the
      exchange of a light pseudoscalar, and analyze its impact on both direct and
      indirect detection experiments. We show that this candidate can accommodate the
      long-standing DAMA modulated signal and yet be compatible with all exclusion
      limits at 99(S)% C.L. This result holds for natural choices of the pseudoscalar
      quark couplings (e.g., flavor universal), which give rise to a significant
      enhancement of the dark matter-proton coupling with respect to the coupling to
      neutrons. We also find that this candidate can accommodate the observed 1-3 GeV
      gamma-ray excess at the Galactic center and at the same time have the correct
      relic density today. The model could be tested with measurements of rare meson
      decays, flavor changing processes, and searches for axionlike particles with mass
      in the MeV range.

PMID- 25615458
TI  - New physics in resonant production of Higgs boson pairs.
AB  - We advocate a search for an extended scalar sector at the LHC via hh production,
      where h is the 125 GeV Higgs boson. A resonance feature in the hh invariant mass
      is a smoking gun of an s-channel heavy Higgs resonance, H. With one h decaying to
      two photons and the other decaying to b quarks, the resonant signal may be
      discoverable above the hh continuum background for M(H)<1  TeV. The product of
      the scalar and top Yukawa couplings can be measured to better than 10%-20%
      accuracy, and its sign can be inferred from the hh line shape via interference
      effects.

PMID- 25615459
TI  - Can the differences in the determinations of V(ub) and V(cb) be explained by new
      physics?
AB  - The precise determination of the Cabibbo-Kobayashi-Maskawa elements V(ub) and
      V(ub) is crucial for any new physics analysis in the flavor sector. Their values
      can be determined from several tree-level decays: V(ub) can be extracted from B
      >Dlnu and B->D(*)lnu while V(ub) can be obtained from B->pilnu, B->rholnu, and B
      >taunu. In addition, for both V(ub) and V(ub) an inclusive determination is
      available. There is a long lasting discrepancy between the inclusive and
      exclusive determinations which recently even increased for V(ub) above the 3sigma
      level. In this Letter we study the possible effect of new physics on the
      inclusive and exclusive determination of V(ub) and V(ub) in a model independent
      way. We find that there is only one operator corresponding to a modified W
      coupling which can achieve this. However, respecting SU(2) gauge invariance at
      the high scale this would lead to very large violations of the Z to bb coupling
      not compatible with experiment. Therefore, we conclude that a new physics
      explanation of the difference between the inclusive and exclusive determination
      of V(ub) and V(ub) is currently ruled out. Therefore, the discrepancies must be
      due to underestimated uncertainties in the theoretical and/or the experimental
      analysis.

PMID- 25615460
TI  - Hadronic light-by-light scattering contribution to the muon anomalous magnetic
      moment from lattice QCD.
AB  - The most compelling possibility for a new law of nature beyond the four
      fundamental forces comprising the standard model of high-energy physics is the
      discrepancy between measurements and calculations of the muon anomalous magnetic
      moment. Until now a key part of the calculation, the hadronic light-by-light
      contribution, has only been accessible from models of QCD, the quantum
      description of the strong force, whose accuracy at the required level may be
      questioned. A first principles calculation with systematically improvable errors
      is needed, along with the upcoming experiments, to decisively settle the matter.
      For the first time, the form factor that yields the light-by-light scattering
      contribution to the muon anomalous magnetic moment is computed in such a
      framework, lattice QCD+QED and QED. A nonperturbative treatment of QED is used
      and checked against perturbation theory. The hadronic contribution is calculated
      for unphysical quark and muon masses, and only the diagram with a single quark
      loop is computed for which statistically significant signals are obtained.
      Initial results are promising, and the prospect for a complete calculation with
      physical masses and controlled errors is discussed. 

PMID- 25615461
TI  - Nuclear neutron-proton contact and the photoabsorption cross section.
AB  - The nuclear neutron-proton contact is introduced, generalizing Tan's work, and
      evaluated from medium energy nuclear photodisintegration experiments. To this end
      we reformulate the quasideuteron model of nuclear photodisintegration and
      establish the bridge between the Levinger constant and the contact. Using
      experimental evaluations of Levinger's constant, we extract the value of the
      neutron-proton contact in finite nuclei and in symmetric nuclear matter. Assuming
      isospin symmetry we propose to evaluate the neutron-neutron contact through the
      measurement of photonuclear spin correlated neutron-proton pairs. 

PMID- 25615462
TI  - Spectral structure of electron antineutrinos from nuclear reactors.
AB  - Recent measurements of the positron energy spectrum obtained from inverse beta
      decay interactions of reactor electron antineutrinos show an excess in the 4 to 6
      MeV region relative to current predictions. First-principles calculations of
      fission and beta decay processes within a typical pressurized water reactor core
      identify prominent fission daughter isotopes as a possible origin for this
      excess. These calculations also predict percent-level substructures in the
      antineutrino spectrum due to Coulomb effects in beta decay. Precise measurement
      of these substructures can elucidate the nuclear processes occurring within
      reactors. These substructures can be a systematic issue for measurements
      utilizing the detailed spectral shape. 

PMID- 25615463
TI  - Relativistic Coulomb excitation within the time dependent superfluid local
      density approximation.
AB  - Within the framework of the unrestricted time-dependent density functional
      theory, we present for the first time an analysis of the relativistic Coulomb
      excitation of the heavy deformed open shell nucleus (238)U. The approach is based
      on the superfluid local density approximation formulated on a spatial lattice
      that can take into account coupling to the continuum, enabling self-consistent
      studies of superfluid dynamics of any nuclear shape. We compute the energy
      deposited in the target nucleus as a function of the impact parameter, finding it
      to be significantly larger than the estimate using the Goldhaber-Teller model.
      The isovector giant dipole resonance, the dipole pygmy resonance, and giant
      quadrupole modes are excited during the process. The one-body dissipation of
      collective dipole modes is shown to lead a damping width Gamma(?)~0.4  MeV and
      the number of preequilibrium neutrons emitted has been quantified.

PMID- 25615464
TI  - Measurement of the gravity-field curvature by atom interferometry.
AB  - We present the first direct measurement of the gravity-field curvature based on
      three conjugated atom interferometers. Three atomic clouds launched in the
      vertical direction are simultaneously interrogated by the same atom
      interferometry sequence and used to probe the gravity field at three equally
      spaced positions. The vertical component of the gravity-field curvature generated
      by nearby source masses is measured from the difference between adjacent gravity
      gradient values. Curvature measurements are of interest in geodesy studies and
      for the validation of gravitational models of the surrounding environment. The
      possibility of using such a scheme for a new determination of the Newtonian
      constant of gravity is also discussed. 

PMID- 25615465
TI  - Observation of a four-electron Auger process in near-K-edge photoionization of
      singly charged carbon ions.
AB  - Single, double, and triple ionization of C(1+) ions by single photons is
      investigated in the energy range of 286-326 eV, i.e., in the range from the
      lowest-energy K-vacancy resonances to well beyond the K-shell ionization
      threshold. Clear signatures of C(1+)(1s2s(2)2p(2) (2)D,(2)P) resonances are found
      in the triple-ionization channel. The only possible mechanism producing
      C(4+)(1s(2)) via these resonances is direct triple-Auger decay, i.e., a four
      electron process with simultaneous emission of three electrons.

PMID- 25615466
TI  - Atomic masses of tritium and helium-3.
AB  - By measuring the cyclotron frequency ratios of (3)He(+) to HD(+) and T(+) to
      HD(+), and using HD(+) as a mass reference, we obtain new atomic masses for (3)He
      and T. Our results are M[(3)He]=3.016 029 322 43(19)  u and M[T]=3.016 049 281
      78(19)  u, where the uncertainty includes an uncertainty of 0.12 nu in the mass
      reference. Allowing for cancellation of common systematic errors, we find the Q
      value for tritium beta decay to be (M[T]-M[(3)He])c(2)=18 592.01(7)  eV. This
      allows an improved test of systematics in measurements of tritium beta decay that
      set limits on neutrino mass.

PMID- 25615467
TI  - Body-assisted van der Waals interaction between excited atoms.
AB  - We present a formula for the body-assisted van der Waals interaction potential
      between two atoms, one or both being prepared in an excited energy eigenstate.
      The presence of an arbitrary arrangement for a material environment is taken into
      account via the Green function. The resulting formula supports one of two
      conflicting findings recorded. The consistency of our formula is investigated by
      applying it for the case of two atoms in free space and comparing the resulting
      expression with the one found from the limiting Casimir-Polder potential between
      an excited atom and a small dielectric sphere. 

PMID- 25615468
TI  - Route to chaos in optomechanics.
AB  - We establish the emergence of chaotic motion in optomechanical systems. Chaos
      appears at negative detuning for experimentally accessible values of the pump
      power and other system parameters. We describe the sequence of period-doubling
      bifurcations that leads to chaos and state the experimentally observable
      signatures in the optical spectrum. In addition to the semiclassical dynamics, we
      analyze the possibility of chaotic motion in the quantum regime. We find that
      quantum mechanics protects the optomechanical system against irregular dynamics,
      such that simple periodic orbits reappear and replace the classically chaotic
      motion. In this way observation of the dynamical signatures makes it possible to
      pin down the crossover from quantum to classical mechanics. 

PMID- 25615469
TI  - Experimental demonstration of enhanced self-amplified spontaneous emission by an
      optical klystron.
AB  - We report the first experimental evidence of enhancement of self-amplified
      spontaneous emission, due to the use of an optical klystron. In this free
      electron laser scheme, a relativistic electron beam passes through two
      undulators, separated by a dispersive section. The latter converts the electron
      beam energy modulation produced in the first undulator in density modulation,
      thus enhancing the free-electron laser gain. The experiment has been carried out
      at the FERMI facility in Trieste. Powerful radiation has been produced in the
      extreme ultraviolet range, with an intensity a few orders of magnitude larger
      than in pure self-amplified spontaneous emission mode. Data have been benchmarked
      with an existing theoretical model. 

PMID- 25615470
TI  - Time-driven superoscillations with negative refraction.
AB  - The flat-lens concept based on negative refraction proposed by Veselago in 1968
      has been mostly investigated in the monochromatic regime. It was recently
      recognized that time development of the superlensing effect discovered in 2000 by
      Pendry is yet to be assessed and may spring surprises: Time-dependent
      illumination could improve the spatial resolution of the focusing. We investigate
      dynamics of flexural wave focusing by a 45 degrees -tilted square lattice of
      circular holes drilled in a duralumin plate. Time-resolved experiments reveal
      that the focused image shrinks with time below the diffraction limit, with a
      lateral resolution increasing from 0.8lambda to 0.35lambda, whereas focusing
      under harmonic excitation remains diffraction limited. Modal analysis reveals the
      role in pulse reconstruction of radiating lens resonances, which repeatedly self
      synchronize at the focal spot to shape a superoscillating field. 

PMID- 25615471
TI  - Indentation of ultrathin elastic films and the emergence of asymptotic isometry.
AB  - We study the indentation of a thin elastic film floating at the surface of a
      liquid. We focus on the onset of radial wrinkles at a threshold indentation depth
      and the evolution of the wrinkle pattern as indentation progresses far beyond
      this threshold. Comparison between experiments on thin polymer films and
      theoretical calculations shows that the system very quickly reaches the far from
      threshold regime, in which wrinkles lead to the relaxation of azimuthal
      compression. Furthermore, when the indentation depth is sufficiently large that
      the wrinkles cover most of the film, we recognize a novel mechanical response in
      which the work of indentation is transmitted almost solely to the liquid, rather
      than to the floating film. We attribute this unique response to a nontrivial
      isometry attained by the deformed film, and we discuss the scaling laws and the
      relevance of similar isometries to other systems in which a confined sheet is
      subjected to weak tensile loads. 

PMID- 25615472
TI  - Sustainable drag reduction in turbulent Taylor-Couette flows by depositing
      sprayable superhydrophobic surfaces.
AB  - We demonstrate a reduction in the measured inner wall shear stress in moderately
      turbulent Taylor-Couette flows by depositing sprayable superhydrophobic
      microstructures on the inner rotor surface. The magnitude of reduction becomes
      progressively larger as the Reynolds number increases up to a value of 22% at
      Re=8.0*10(4). We show that the mean skin friction coefficient C(f) in the
      presence of the superhydrophobic coating can be fitted to a modified Prandtl-von
      Karman-type relationship of the form (C(f)/2)(-1/2)=Mln
      (Re(C(f)/2)(1/2))+N+(b/Deltar)Re(C(f)/2)(1/2) from which we extract an effective
      slip length of b~19  MUm. The dimensionless effective slip length
      b(+)=b/delta(nu), where delta(nu) is the viscous length scale, is the key
      parameter that governs the drag reduction and is shown to scale as b(+)~Re(1/2)
      in the limit of high Re.

PMID- 25615473
TI  - Magnetically assisted fast ignition.
AB  - Fast ignition (FI) is investigated via integrated particle-in-cell simulation
      including both generation and transport of fast electrons, where petawatt
      ignition lasers of 2 ps and compressed targets of a peak density of 300  g cm(-3)
      and areal density of 0.49  g cm(-2) at the core are taken. When a 20 MG static
      magnetic field is imposed across a conventional cone-free target, the energy
      coupling from the laser to the core is enhanced by sevenfold and reaches 14%.
      This value even exceeds that obtained using a cone-inserted target, suggesting
      that the magnetically assisted scheme may be a viable alternative for FI. With
      this scheme, it is demonstrated that two counterpropagating, 6 ps, 6 kJ lasers
      along the magnetic field transfer 12% of their energy to the core, which is then
      heated to 3 keV.

PMID- 25615474
TI  - Alfven acoustic channel for ion energy in high-beta tokamak plasmas.
AB  - When the plasma beta (ratio of thermal to magnetic pressure) in the core of a
      tokamak is raised to values of several percent, as required for a thermonuclear
      fusion reactor, continuous spectra of long-wavelength slow magnetosonic waves
      enter the frequency band occupied by continuous spectra of shear Alfven waves. It
      is found that these two branches can couple strongly, so that Alfven modes that
      are resonantly driven by suprathermal ions transfer some of their energy to sound
      waves. Since sound waves are heavily damped by thermal ion Landau resonances,
      these results reveal a new energy channel that contributes to the damping of
      Alfvenic instabilities and the noncollisional heating of bulk ions, with
      potentially important consequences for confinement and fusion performance. 

PMID- 25615475
TI  - Saturable absorption of an x-ray free-electron-laser heated solid-density
      aluminum plasma.
AB  - High-intensity x-ray pulses from an x-ray free-electron laser are used to heat
      and probe a solid-density aluminum sample. The photon-energy-dependent
      transmission of the heating beam is studied through the use of a photodiode.
      Saturable absorption is observed, with the resulting transmission differing
      significantly from the cold case, in good agreement with atomic-kinetics
      simulations. 

PMID- 25615476
TI  - Observation of the Leggett-Rice effect in a unitary Fermi gas.
AB  - We observe that the diffusive spin current in a strongly interacting degenerate
      Fermi gas of (40)K precesses about the local magnetization. As predicted by
      Leggett and Rice, precession is observed both in the Ramsey phase of a spin-echo
      sequence, and in the nonlinearity of the magnetization decay. At unitarity, we
      measure a Leggett-Rice parameter gamma=1.08(9) and a bare transverse spin
      diffusivity D(0)(?)=2.3(4)h/m for a normal-state gas initialized with full
      polarization and at one-fifth of the Fermi temperature, where m is the atomic
      mass. One might expect gamma=0 at unitarity, where two-body scattering is purely
      dissipative. We observe gamma->0 as temperature is increased towards the Fermi
      temperature, consistent with calculations that show the degenerate Fermi sea
      restores a nonzero gamma. Tuning the scattering length a, we find that a sign
      change in gamma occurs in the range 0<(k(F)a)(-1)?1.3, where k(F) is the Fermi
      momentum. We discuss how gamma reveals the effective interaction strength of the
      gas, such that the sign change in gamma indicates a switching of branch between a
      repulsive and an attractive Fermi gas.

PMID- 25615477
TI  - Selective detection of angular-momentum-polarized Auger electrons by atomic
      stereography.
AB  - When a core level is excited by circularly polarized light, the angular momentum
      of light is transferred to the emitted photoelectron, which can be confirmed by
      the parallax shift of the forward focusing peak (FFP) direction in a stereograph
      of atomic arrangement. No angular momentum has been believed to be transferred to
      normal Auger electrons resulting from the decay process filling core hole after
      photoelectron ejection. We succeeded in detecting a non-negligible circular
      dichroism contrast in a normal Auger electron diffraction from a nonmagnetic
      Cu(001) surface far off from the absorption threshold. Moreover, we detected
      angular-momentum-polarized Cu L(3)M(4,5)M(4,5) Auger electrons at the L(3)
      absorption threshold, where the excited core electron is trapped at the
      conduction band. From the kinetic energy dependence of the Auger electron FFP
      parallax shift, we found that the angular momentum is transferred to the Auger
      electron most effectively in the case of the (1)S(0) two-hole creation.

PMID- 25615478
TI  - Superhard BC(3) in cubic diamond structure.
AB  - We solve the crystal structure of recently synthesized cubic BC(3) using an
      unbiased swarm structure search, which identifies a highly symmetric BC(3) phase
      in the cubic diamond structure (d-BC(3)) that contains a distinct B-B bonding
      network along the body diagonals of a large 64-atom unit cell. Simulated x-ray
      diffraction and Raman peaks of d-BC(3) are in excellent agreement with
      experimental data. Calculated stress-strain relations of d-BC(3) demonstrate its
      intrinsic superhard nature and reveal intriguing sequential bond-breaking modes
      that produce superior ductility and extended elasticity, which are unique among
      superhard solids. The present results establish the first boron carbide in the
      cubic diamond structure with remarkable properties, and these new findings also
      provide insights for exploring other covalent solids with complex bonding
      configurations.

PMID- 25615479
TI  - Scale-free phase field theory of dislocations.
AB  - According to recent experimental and numerical investigations, if a
      characteristic length (such as grain size) of a specimen is in the submicron size
      regime, several new interesting phenomena emerge during the deformation. Since in
      such systems boundaries play a crucial role, to model the plastic response it is
      crucial to determine the dislocation distribution near the boundaries. In this
      Letter, a phase-field-type continuum theory of the time evolution of an ensemble
      of parallel edge dislocations with identical Burgers vectors, corresponding to
      the dislocation geometry near internal boundaries, is presented. Since the
      dislocation-dislocation interaction is scale free (1/r), apart from the average
      dislocation spacing the theory cannot contain any length scale parameter. As
      shown, the continuum theory suggested is able to recover the dislocation
      distribution near boundaries obtained by discrete dislocation dynamics
      simulations. 

PMID- 25615480
TI  - Nanoscale directional motion towards regions of stiffness.
AB  - How to induce nanoscale directional motion via some intrinsic mechanisms
      pertaining to a nanosystem remains a challenge in nanotechnology. Here we show
      via molecular dynamics simulations that there exists a fundamental driving force
      for a nanoscale object to move from a region of lower stiffness toward one of
      higher stiffness on a substrate. Such nanoscale directional motion is induced by
      the difference in effective van der Waals potential energy due to the variation
      in stiffness of the substrate; i.e., all other conditions being equal, a
      nanoscale object on a stiffer substrate has lower van der Waals potential energy.
      This fundamental law of nanoscale directional motion could lead to promising
      routes for nanoscale actuation and energy conversion. 

PMID- 25615481
TI  - Following the evolution of hard sphere glasses in infinite dimensions under
      external perturbations: compression and shear strain.
AB  - We consider the adiabatic evolution of glassy states under external
      perturbations. The formalism we use is very general. Here we use it for infinite
      dimensional hard spheres where an exact analysis is possible. We consider
      perturbations of the boundary, i.e., compression or (volume preserving) shear
      strain, and we compute the response of glassy states to such perturbations:
      pressure and shear stress. We find that both quantities overshoot before the
      glass state becomes unstable at a spinodal point where it melts into a liquid (or
      yields). We also estimate the yield stress of the glass. Finally, we study the
      stability of the glass basins towards breaking into sub-basins, corresponding to
      a Gardner transition. We find that close to the dynamical transition, glasses
      undergo a Gardner transition after an infinitesimal perturbation. 

PMID- 25615482
TI  - Spin correlation in O(2) chemisorption on Ni(111).
AB  - Molecular oxygen (O(2)) is a paramagnetic linear molecule, yet how its electron
      spin affects the chemisorption probability remains unclear. We here present the
      first spin- and alignment-resolved O(2) chemisorption experiment conducted with a
      single spin-rotational state-selected O(2) beam and a magnetized Ni(111) surface.
      The results show that the O(2) sticking probability is higher when its spin is
      oriented antiparallel to the majority spin direction of the Ni substrate. The
      spin dependence becomes more significant at low translational energy, and amounts
      to over 40% at thermal energy. This strong spin effect suggests that incident
      O(2) molecules keep high spin polarizations even at the position of the
      dissociation barrier.

PMID- 25615483
TI  - Interplay of spin-orbit interactions, dimensionality, and octahedral rotations in
      semimetallic SrIrO(3).
AB  - We employ reactive molecular-beam epitaxy to synthesize the metastable perovskite
      SrIrO(3) and utilize in situ angle-resolved photoemission to reveal its
      electronic structure as an exotic narrow-band semimetal. We discover remarkably
      narrow bands which originate from a confluence of strong spin-orbit interactions,
      dimensionality, and both in- and out-of-plane IrO(6) octahedral rotations. The
      partial occupation of numerous bands with strongly mixed orbital characters
      signals the breakdown of the single-band Mott picture that characterizes its
      insulating two-dimensional counterpart, Sr(2)IrO(4), illustrating the power of
      structure-property relations for manipulating the subtle balance between spin
      orbit interactions and electron-electron interactions.

PMID- 25615484
TI  - Spatial correlations and the insulating phase of the high-T(c) cuprates: insights
      from a configuration-interaction-based solver for dynamical mean field theory.
AB  - A recently proposed configuration-interaction-based impurity solver is used in
      combination with the single-site and four-site cluster dynamical mean field
      approximations to investigate the three-band copper oxide model believed to
      describe the electronic structure of high transition temperature copper-oxide
      superconductors. Use of the configuration interaction solver enables verification
      of the convergence of results with respect to the number of bath orbitals. The
      spatial correlations included in the cluster approximation substantially shift
      the metal-insulator phase boundary relative to the prediction of the single-site
      approximation and increase the predicted energy gap of the insulating phase by
      about 1 eV above the single-site result. Vertex corrections occurring in the four
      site approximation act to dramatically increase the value of the optical
      conductivity near the gap edge, resulting in better agreement with the data. The
      calculations reveal two distinct correlated insulating states: the "magnetically
      correlated insulator," in which nontrivial intersite correlations play an
      essential role in stabilizing the insulating state, and the strongly correlated
      insulator, in which local physics suffices. Comparison of the calculations to the
      data places the cuprates in the magnetically correlated Mott insulator regime. 

PMID- 25615485
TI  - Non-Kondo-like electronic structure in the correlated rare-earth hexaboride
      YbB(6).
AB  - We present angle-resolved photoemission studies on the rare-earth-hexaboride
      YbB(6), which has recently been predicted to be a topological Kondo insulator.
      Our data do not agree with the prediction and instead show that YbB(6) exhibits a
      novel topological insulator state in the absence of a Kondo mechanism. We find
      that the Fermi level electronic structure of YbB(6) has three 2D Dirac cone like
      surface states enclosing the Kramers's points, while the f orbital that would be
      relevant for the Kondo mechanism is ~1  eV below the Fermi level. Our first
      principles calculation shows that the topological state that we observe in YbB(6)
      is due to an inversion between Yb d and B p bands. These experimental and
      theoretical results provide a new approach for realizing novel correlated
      topological insulator states in rare-earth materials.

PMID- 25615486
TI  - Spatially resolved transient dynamics of charge density waves in NbSe(3).
AB  - We have developed methods for acquiring temporally and spatially resolved
      spectrograms of the velocity of sliding charge-density waves (CDWs), allowing
      unprecedented access to CDW dynamics. Complex transients arising from the
      interplay between elastic and plastic processes occur when the driving field
      direction is reversed. A transient spectral component due to shear elasticity can
      be unambiguously identified, and allows the most direct determination to date of
      the CDW's shear elastic modulus. Near current contacts, initially elastic
      displacements are followed by an elastic-to-plastic transition. A simple model
      provides a semiquantitative account of many aspects of these transients. 

PMID- 25615487
TI  - Determination of the nitrogen vacancy as a shallow compensating center in GaN
      doped with divalent metals.
AB  - We report accurate energetics of defects introduced in GaN on doping with
      divalent metals, focusing on the technologically important case of Mg doping,
      using a model that takes into consideration both the effect of hole localization
      and dipolar polarization of the host material, and includes a well-defined
      reference level. Defect formation and ionization energies show that divalent
      dopants are counterbalanced in GaN by nitrogen vacancies and not by holes, which
      explains both the difficulty in achieving p-type conductivity in GaN and the
      associated major spectroscopic features, including the ubiquitous 3.46 eV
      photoluminescence line, a characteristic of all lightly divalent-metal-doped GaN
      materials that has also been shown to occur in pure GaN samples. Our results give
      a comprehensive explanation for the observed behavior of GaN doped with low
      concentrations of divalent metals in good agreement with relevant experiment. 

PMID- 25615488
TI  - Shot noise induced by nonequilibrium spin accumulation.
AB  - When an electric current passes across a potential barrier, the partition process
      of electrons at the barrier gives rise to the shot noise, reflecting the discrete
      nature of the electric charge. Here we report the observation of excess shot
      noise connected with a spin current which is induced by a nonequilibrium spin
      accumulation in an all-semiconductor lateral spin-valve device. We find that this
      excess shot noise is proportional to the spin current. Additionally, we determine
      quantitatively the spin-injection-induced electron temperature by measuring the
      current noise. Our experiments show that spin accumulation driven shot noise
      provides a novel means of investigating nonequilibrium spin transport. 

PMID- 25615489
TI  - Shot noise as a probe of spin-polarized transport through single atoms.
AB  - Single atoms on Au(111) surfaces have been contacted with the Au tip of a low
      temperature scanning tunneling microscope. The shot noise of the current through
      these contacts has been measured up to frequencies of 120 kHz and Fano factors
      have been determined to characterize the transport channels. The noise at Fe and
      Co atoms, the latter displaying a Kondo effect, indicates spin-polarized
      transport through a single channel. Transport calculations reproduce this
      observation. 

PMID- 25615490
TI  - Proximity-induced ferromagnetism in graphene revealed by the anomalous Hall
      effect.
AB  - We demonstrate the anomalous Hall effect (AHE) in single-layer graphene exchange
      coupled to an atomically flat yttrium iron garnet (YIG) ferromagnetic thin film.
      The anomalous Hall conductance has magnitude of ~0.09(2e(2)/h) at low
      temperatures and is measurable up to ~300  K. Our observations indicate not only
      proximity-induced ferromagnetism in graphene/YIG with a large exchange
      interaction, but also enhanced spin-orbit coupling that is believed to be
      inherently weak in ideal graphene. The proximity-induced ferromagnetic order in
      graphene can lead to novel transport phenomena such as the quantized AHE which
      are potentially useful for spintronics.

PMID- 25615491
TI  - Induced topological phases at the boundary of 3D topological superconductors.
AB  - We present tight-binding models of 3D topological superconductors in class DIII
      that support a variety of winding numbers. We show that gapless Majorana surface
      states emerge at their boundary in agreement with the bulk-boundary
      correspondence. At the presence of a Zeeman field, the surface states become
      gapped and the boundary behaves as a 2D superconductor in class D. Importantly,
      the 2D and 3D winding numbers are in agreement, signifying that the topological
      phase of the boundary is induced by the phase of the 3D bulk. Hence, the boundary
      of a 3D topological superconductor in class DIII can be used for the robust
      realization of localized Majorana zero modes. 

PMID- 25615492
TI  - Thermal Hall effect and geometry with torsion.
AB  - We formulate a geometric framework that allows us to study momentum and energy
      transport in nonrelativistic systems. It amounts to a coupling of the
      nonrelativistic system to the Newton-Cartan (NC) geometry with torsion. The
      approach generalizes the classic Luttinger's formulation of thermal transport. In
      particular, we clarify the geometric meaning of the fields conjugated to energy
      and energy current. These fields describe the geometric background with
      nonvanishing temporal torsion. We use the developed formalism to construct the
      equilibrium partition function of a nonrelativistic system coupled to the NC
      geometry in 2+1 dimensions and to derive various thermodynamic relations. 

PMID- 25615493
TI  - Pressure-induced inhomogeneous chiral-spin ground state in FeGe.
AB  - (57)Fe nuclear forward scattering on the chiral magnet FeGe reveals an extremely
      large precursor phase region above the helimagnetic ordering temperature T(C)(p)
      and beyond the pressure-induced quantum phase transition at 19 GPa. The decrease
      of the magnetic hyperfine field ?B(hf)? with pressure is accompanied by a large
      increase of the width of the distribution of ?B(hf)?, indicating a strong
      quasistatic inhomogeneity of the magnetic states in the precursor region.
      Hyperfine fields of the order of 4 T (equivalent to a magnetic moment
      MU(Fe)~0.4MU(B)) persist up to 28.5 GPa. No signatures of magnetic order have
      been found at about 31 GPa. The results, supported by ab initio calculations,
      suggest that chiral magnetic precursor phenomena, such as an inhomogeneous chiral
      spin state, are vastly enlarged due to increasing spin fluctuations as FeGe is
      tuned to its quantum phase transition.

PMID- 25615494
TI  - Phonon-mediated electron transport through CaO thin films.
AB  - Scanning tunneling microscopy has developed into a powerful tool for the
      characterization of conductive surfaces, for which the overlap of tip and sample
      wave functions determines the image contrast. On insulating layers, as the CaO
      thin film grown on Mo(001) investigated here, direct overlap between initial and
      final states is not enabled anymore and electrons are transported via hopping
      through the conduction-band states of the oxide. Carrier transport is accompanied
      by strong phonon excitations in this case, imprinting an oscillatory signature on
      the differential conductance spectra of the system. The phonons show a
      characteristic spatial dependence and become softer around lattice irregularities
      in the oxide film, such as dislocation lines. 

PMID- 25615495
TI  - Framing anomaly in the effective theory of the fractional quantum Hall effect.
AB  - We consider the geometric part of the effective action for the fractional quantum
      Hall effect (FQHE). It is shown that accounting for the framing anomaly of the
      quantum Chern-Simons theory is essential to obtain the correct gravitational
      linear response functions. In the lowest order in gradients, the linear response
      generating functional includes Chern-Simons, Wen-Zee, and gravitational Chern
      Simons terms. The latter term has a contribution from the framing anomaly which
      fixes the value of thermal Hall conductivity and contributes to the Hall
      viscosity of the FQH states on a sphere. We also discuss the effects of the
      framing anomaly on linear responses for non-Abelian FQH states. 

PMID- 25615496
TI  - Topology and interactions in a frustrated slab: tuning from Weyl semimetals to
      C>1 fractional Chern insulators.
AB  - We show that, quite generically, a [111] slab of spin-orbit coupled pyrochlore
      lattice exhibits surface states whose constant energy curves take the shape of
      Fermi arcs, localized to different surfaces depending on their quasimomentum.
      Remarkably, these persist independently of the existence of Weyl points in the
      bulk. Considering interacting electrons in slabs of finite thickness, we find a
      plethora of known fractional Chern insulating phases, to which we add the
      discovery of a new higher Chern number state which is likely a generalization of
      the Moore-Read fermionic fractional quantum Hall state. By contrast, in the three
      dimensional limit, we argue for the absence of gapped states of the flat surface
      band due to a topologically protected coupling of the surface to gapless states
      in the bulk. We comment on generalizations as well as experimental perspectives
      in thin slabs of pyrochlore iridates. 

PMID- 25615497
TI  - Experimental detection of a Majorana mode in the core of a magnetic vortex inside
      a topological insulator-superconductor Bi(2)Te(3)/NbSe(2) heterostructure.
AB  - Majorana fermions have been intensively studied in recent years for their
      importance to both fundamental science and potential applications in topological
      quantum computing. They are predicted to exist in a vortex core of
      superconducting topological insulators. However, it is extremely difficult to
      distinguish them experimentally from other quasiparticle states for the tiny
      energy difference between Majorana fermions and these states, which is beyond the
      energy resolution of most available techniques. Here, we circumvent the problem
      by systematically investigating the spatial profile of the Majorana mode and the
      bound quasiparticle states within a vortex in Bi(2)Te(3) films grown on a
      superconductor NbSe(2). While the zero bias peak in local conductance splits
      right off the vortex center in conventional superconductors, it splits off at a
      finite distance ~20  nm away from the vortex center in Bi(2)Te(3). This unusual
      splitting behavior has never been observed before and could be possibly due to
      the Majorana fermion zero mode. While the Majorana mode is destroyed by the
      interaction between vortices, the zero bias peak splits as a conventional
      superconductor again. This work provides self-consistent evidences of Majorana
      fermions and also suggests a possible route to manipulating them.

PMID- 25615498
TI  - Longitudinal and transverse Zeeman ladders in the Ising-like chain
      antiferromagnet BaCo(2)V(2)O(8).
AB  - We explore the spin dynamics emerging from the Neel phase of the chain compound
      antiferromagnet BaCo(2)V(2)O(8). Our inelastic neutron scattering study reveals
      unconventional discrete spin excitations, so-called Zeeman ladders, understood in
      terms of spinon confinement, due to the interchain attractive linear potential.
      These excitations consist of two interlaced series of modes, respectively, with
      transverse and longitudinal polarization. The latter, which correspond to a
      longitudinal fluctuation of the ordered moment, have no classical counterpart and
      are related to the zero-point fluctuations that weaken the ordered moment in
      weakly coupled quantum chains. Our analysis reveals that BaCo(2)V(2)O(8), with
      moderate Ising anisotropy and sizable interchain interactions, remarkably
      fulfills the conditions necessary for the observation of discrete long-lived
      longitudinal excitations.

PMID- 25615499
TI  - Sign change of the spin Hall effect due to electron correlation in nonmagnetic
      CuIr alloys.
AB  - Recently, a positive spin Hall angle (SHA) of 0.021 was observed experimentally
      in nonmagnetic CuIr alloys [Niimi et al, Phys. Rev. Lett. 106, 126601 (2011)] and
      attributed predominantly to an extrinsic skew scattering mechanism, while a
      negative SHA was obtained from ab initio calculations [Fedorov et al, Phys. Rev.
      B 88, 085116 (2013)], using consistent definitions of the SHA. We reconsider the
      SHA in CuIr alloys, with the effects of the local electron correlation U in 5d
      orbitals of Ir impurities, included by the quantum Monte Carlo method. We found
      that the SHA is negative if we ignore such local electron correlation, but
      becomes positive once U approaches a realistic value. This may open up a way to
      control the sign of the SHA by manipulating the occupation number of impurities. 

PMID- 25615500
TI  - Confinement-deconfinement transition as an indication of spin-liquid-type
      behavior in Na(2)IrO(3).
AB  - We use ultrafast optical spectroscopy to observe binding of charged single
      particle excitations (SE) in the magnetically frustrated Mott insulator
      Na(2)IrO(3). Above the antiferromagnetic ordering temperature (T(N)) the system
      response is due to both Hubbard excitons (HE) and their constituent unpaired SE.
      The SE response becomes strongly suppressed immediately below T(N). We argue that
      this increase in binding energy is due to a unique interplay between the
      frustrated Kitaev and the weak Heisenberg-type ordering term in the Hamiltonian,
      mediating an effective interaction between the spin-singlet SE. This interaction
      grows with distance causing the SE to become trapped in the HE, similar to quark
      confinement inside hadrons. This binding of charged particles, induced by
      magnetic ordering, is a result of a confinement-deconfinement transition of spin
      excitations. This observation provides evidence for spin liquid type behavior
      which is expected in Na(2)IrO(3).

PMID- 25615502
TI  - Anisotropic local modification of crystal field levels in Pr-based pyrochlores: a
      muon-induced effect modeled using density functional theory.
AB  - Although muon spin relaxation is commonly used to probe local magnetic order,
      spin freezing, and spin dynamics, we identify an experimental situation in which
      the measured response is dominated by an effect resulting from the muon-induced
      local distortion rather than the intrinsic behavior of the host compound. We
      demonstrate this effect in some quantum spin ice candidate materials
      Pr(2)B(2)O(7) (B=Sn, Zr, Hf), where we detect a static distribution of magnetic
      moments that appears to grow on cooling. Using density functional theory we show
      how this effect can be explained via a hyperfine enhancement arising from a
      splitting of the non-Kramers doublet ground states on Pr ions close to the muon,
      which itself causes a highly anisotropic distortion field. We provide a
      quantitative relationship between this effect and the measured temperature
      dependence of the muon relaxation and discuss the relevance of these observations
      to muon experiments in other magnetic materials.

PMID- 25615501
TI  - Spectroscopy of surface-induced noise using shallow spins in diamond.
AB  - We report on the noise spectrum experienced by few nanometer deep nitrogen
      vacancy centers in diamond as a function of depth, surface coating, magnetic
      field and temperature. Analysis reveals a double-Lorentzian noise spectrum
      consistent with a surface electronic spin bath in the low frequency regime, along
      with a faster noise source attributed to surface-modified phononic coupling.
      These results shed new light on the mechanisms responsible for surface noise
      affecting shallow spins at semiconductor interfaces, and suggests possible
      directions for further studies. We demonstrate dynamical decoupling from the
      surface noise, paving the way to applications ranging from nanoscale NMR to
      quantum networks. 

PMID- 25615503
TI  - Silo collapse under granular discharge.
AB  - We investigate, at a laboratory scale, the collapse of cylindrical shells of
      radius R and thickness t induced by a granular discharge. We measure the critical
      filling height for which the structure fails upon discharge. We observe that the
      silos sustain filling heights significantly above an estimation obtained by
      coupling standard shell-buckling and granular stress distribution theories. Two
      effects contribute to stabilize the structure: (i) below the critical filling
      height, a dynamical stabilization due to granular wall friction prevents the
      localized shell-buckling modes to grow irreversibly; (ii) above the critical
      filling height, collapse occurs before the downward sliding motion of the whole
      granular column sets in, such that only a partial friction mobilization is at
      play. However, we notice also that the critical filling height is reduced as the
      grain size d increases. The importance of grain size contribution is controlled
      by the ratio d/?[Rt]. We rationalize these antagonist effects with a novel fluid
      structure theory both accounting for the actual status of granular friction at
      the wall and the inherent shell imperfections mediated by the grains. This theory
      yields new scaling predictions which are compared with the experimental results.

PMID- 25615504
TI  - Angular and energy distributions of electrons produced in arbitrary biomaterials
      by proton impact.
AB  - We present a simple method for obtaining reliable angular and energy
      distributions of electrons ejected from arbitrary condensed biomaterials by
      proton impact. Relying on a suitable description of the electronic excitation
      spectrum and a physically motivated relation between the ion and electron
      scattering angles, it yields cross sections in rather good agreement with
      experimental data in a broad range of ejection angles and energies, by only using
      as input the target composition and density. The versatility and simplicity of
      the method, which can be also extended to other charged particles, make it
      especially suited for obtaining ionization data for any complex biomaterial
      present in realistic cellular environments. 

PMID- 25615505
TI  - Lateral line layout correlates with the differential hydrodynamic pressure on
      swimming fish.
AB  - The lateral line of fish includes the canal subsystem that detects hydrodynamic
      pressure gradients and is thought to be important in swimming behaviors such as
      rheotaxis and prey tracking. Here, we explore the hypothesis that this sensory
      system is concentrated at locations where changes in pressure are greatest during
      motion through water. Using high-fidelity models of rainbow trout, we mimic the
      flows encountered during swimming while measuring pressure with fine spatial and
      temporal resolution. The variations in pressure for perturbations in body
      orientation and for disturbances to the incoming stream are seen to correlate
      with the sensory network. These findings support a view of the lateral line as a
      "hydrodynamic antenna" that is configured to retrieve flow signals and also
      suggest a physical explanation for the nearly universal sensory layout across
      diverse species. 

PMID- 25615506
TI  - Flow-driven waves and phase-locked self-organization in quasi-one-dimensional
      colonies of Dictyostelium discoideum.
AB  - We report experiments on flow-driven waves in a microfluidic channel containing
      the signaling slime mold Dictyostelium discoideum. The observed cyclic adenosine
      monophosphate (cAMP) wave trains developed spontaneously in the presence of flow
      and propagated with the velocity proportional to the imposed flow velocity. The
      period of the wave trains was independent of the flow velocity. Perturbations of
      flow-driven waves via external periodic pulses of the signaling agent cAMP
      induced 1?1, 2?1, 3?1, and 1?2 frequency responses, reminiscent of Arnold tongues
      in forced oscillatory systems. We expect our observations to be generic to active
      media governed by reaction-diffusion-advection dynamics, where spatially bound
      autocatalytic processes occur under flow conditions. 

PMID- 25615507
TI  - Statistical mechanics of viral entry.
AB  - Viruses that have lipid-membrane envelopes infect cells by fusing with the cell
      membrane to release viral genes. Membrane fusion is known to be hindered by high
      kinetic barriers associated with drastic structural rearrangements-yet viral
      infection, which occurs by fusion, proceeds on remarkably short time scales.
      Here, we present a quantitative framework that captures the principles behind the
      invasion strategy shared by all enveloped viruses. The key to this strategy
      ligand-triggered conformational changes in the viral proteins that pull the
      membranes together-is treated as a set of concurrent, bias field-induced
      activated rate processes. The framework results in analytical solutions for
      experimentally measurable characteristics of virus-cell fusion and enables us to
      express the efficiency of the viral strategy in quantitative terms. The
      predictive value of the theory is validated through simulations and illustrated
      through recent experimental data on influenza virus infection. 

PMID- 25615508
TI  - Antibiotic-induced anomalous statistics of collective bacterial swarming.
AB  - Under sublethal antibiotics concentrations, the statistics of collectively
      swarming Bacillus subtilis transitions from normal to anomalous, with a heavy
      tailed speed distribution and a two-step temporal correlation of velocities. The
      transition is due to changes in the properties of the bacterial motion and the
      formation of a motility-defective subpopulation that self-segregates into
      regions. As a result, both the colonial expansion and the growth rate are not
      affected by antibiotics. This phenomenon suggests a new strategy bacteria employ
      to fight antibiotic stress. 

PMID- 25615509
TI  - Activity-induced phase separation and self-assembly in mixtures of active and
      passive particles.
AB  - We investigate the phase behavior and kinetics of a monodisperse mixture of
      active (i.e., self-propelled) and passive isometric Brownian particles through
      Brownian dynamics simulations and theory. As in a purely active system, motility
      of the active component triggers phase separation into a dense and a dilute
      phase; in the dense phase, we further find active-passive segregation, with
      "rafts" of passive particles in a "sea" of active particles. We find that phase
      separation from an initially disordered mixture can occur with as little as 15%
      of the particles being active. Finally, we show that a system prepared in a
      suitable fully segregated initial state reproducibly self-assembles an active
      "corona," which triggers crystallization of the passive core by initiating a
      compression wave. Our findings are relevant to the experimental pursuit of
      directed self-assembly using active particles. 

PMID- 25615510
TI  - Tunable long range forces mediated by self-propelled colloidal hard spheres.
AB  - Using Brownian dynamics simulations, we systematically study the effective
      interaction between two parallel hard walls in a 2D suspension of self-propelled
      (active) colloidal hard spheres, and we find that the effective force between two
      hard walls can be tuned from a long range repulsion into a long range attraction
      by changing the density of active particles. At relatively high densities, the
      active hard spheres can form a dynamic crystalline bridge, which induces a strong
      oscillating long range dynamic wetting repulsion between the walls. With
      decreasing density, the dynamic bridge gradually breaks, and an intriguing long
      range dynamic depletion attraction arises. A similar effect occurs in a quasi-2D
      suspension of self-propelled colloidal hard spheres by changing the height of the
      confinement. Our results open up new possibilities to manipulate the motion and
      assembly of microscopic objects by using active matter. 

PMID- 25615511
TI  - The effects of extending the spectral information acquired by a photon-counting
      detector for spectral CT.
AB  - Photon-counting x-ray detectors with pulse-height analysis provide spectral
      information that may improve material decomposition and contrast-to-noise ratio
      (CNR) in CT images. The number of energy measurements that can be acquired
      simultaneously on a detector pixel is equal to the number of comparator channels.
      Some spectral CT designs have a limited number of comparator channels, due to the
      complexity of readout electronics. The spectral information could be extended by
      changing the comparator threshold levels over time, sub pixels, or view angle.
      However, acquiring more energy measurements than comparator channels increases
      the noise and/or dose, due to differences in noise correlations across energy
      measurements and decreased dose utilisation. This study experimentally quantified
      the effects of acquiring more energy measurements than comparator channels using
      a bench-top spectral CT system. An analytical and simulation study modeling an
      ideal detector investigated whether there was a net benefit for material
      decomposition or optimal energy weighting when acquiring more energy measurements
      than comparator channels. Experimental results demonstrated that in a two
      threshold acquisition, acquiring the high-energy measurement independently from
      the low-energy measurement increased noise standard deviation in material
      decomposition basis images by factors of 1.5-1.7 due to changes in covariance
      between energy measurements. CNR in energy-weighted images decreased by factors
      of 0.92-0.71. Noise standard deviation increased by an additional factor of
      [Formula: see text] due to reduced dose utilisation. The results demonstrated no
      benefit for two-material decomposition noise or energy-weighted CNR when
      acquiring more energy measurements than comparator channels. Understanding the
      noise penalty of acquiring more energy measurements than comparator channels is
      important for designing spectral detectors and for designing experiments and
      interpreting data from prototype systems with a limited number of comparator
      channels. 

PMID- 25615512
TI  - Role of laparoscopic surgery in the treatment of ulcerative colitis; short- and
      mid-term results.
AB  - OBJECTIVES: Laparoscopy is used more widely for the surgery of ulcerative
      colitis. The objective of this study was a comparison of the surgical and 3-year
      follow-up results of patients treated with conventional and minimally invasive
      methods. MATERIALS AND METHODS: A total of 45 patients received surgery for
      ulcerative colitis, 16 as emergency and 29 as elective cases. Laparoscopy was
      used in 23 and a conventional method in 22 cases. No difference was found between
      the two groups from the aspects of American Society of Anesthesiologists physical
      status (ASA) class, mean body mass index (BMI) and age. There were 4 emergency
      cases in the laparoscopy group, and 12 in the open group. Nineteen elective
      surgeries were performed in the laparoscopy group, and 10 in the open group.
      RESULTS: There was no significant difference between the groups as concerns the
      length of hospital or intensive care unit (ICU) stay, the time to bowel function
      recovery, but the duration of open surgery was significantly shorter. There was
      no difference between the groups in the rate of early postoperative
      complications, whereas among potential late complications, the rates of
      intestinal obstruction (8.7% vs. 45%) and a septic condition (0% vs. 27%) were
      significantly lower in the laparoscopy group. There was a significant improvement
      in the quality of life after surgery in both groups, and better cosmetic results
      were observed in the laparoscopy group. CONCLUSION: Laparoscopy can be used for
      ulcerative colitis both emergency and elective cases, it provides a good quality
      of life and the mid-term rate of complications is lower as compared with open
      surgery.

PMID- 25615513
TI  - Serotonin syndrome caused by fentanyl and methadone in a burn injury.
AB  - Serotonin syndrome is a syndrome identified by a triad of altered mental status,
      neuromuscular overactivity, and autonomic instability caused by the
      overstimulation of serotonin in the central nervous system and periphery.
      Serotonin syndrome may be provoked with the addition or increase in serotonergic
      agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine
      reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors
      as well as other agents with serotonergic properties. Some narcotics, including
      fentanyl and methadone, have these properties and may be associated with the
      development of serotonin syndrome when used in conjunction with other agents.
      Currently, there are no identified case reports of narcotics as the sole agent
      causing serotonin syndrome. This report provides a brief overview of serotonin
      syndrome, particularly with cases involving administration of narcotics such as
      fentanyl and methadone. The case described is the first report associated with
      fentanyl and methadone without the coadministration of other serotonergic agents,
      and a possible drug interaction with voriconazole is discussed. This raises
      awareness of using multiple serotonergic narcotics and the potential
      precipitation of serotonin syndrome. 

PMID- 25615514
TI  - Using in vitro and in vivo models to evaluate the oral bioavailability of
      nutraceuticals.
AB  - Nutraceuticals are the bioactive compounds found in many dietary sources.
      Numerous publications have reported their ability to prevent the development of
      degenerative diseases through modulation of physiological and physiochemical
      processes in living systems. Having sufficient concentration at the target site
      of action is the most critical factor for nutraceuticals to deliver the health
      benefits. For consumers, it is commonly accepted to ingest these bioactive
      components through oral delivery route because it is convenient and cost
      efficient and allows flexible dosing schedule. Thus, it is important to
      understand the oral bioavailability of nutraceuticals to evaluate their
      qualifications as disease preventive agents and to calculate the required
      ingestion dosages. To predict the oral bioavailability of nutraceuticals, many in
      vitro and in vivo models have been developed to reduce the need for frequent
      human pharmacokinetic studies, which are costly and time-consuming and involve
      ethical complications. These models evaluate one or more of the influential
      factors that contribute to the oral bioavailability and are efficient screening
      techniques with the potential of predicting the pharmacokinetic process in
      humans. To accurately predict human oral bioavailability, further research is
      required to develop not only a better correlation between the in vitro and in
      vivo models but also an accurate scaling factor that takes into account
      interspecies variations.

PMID- 25615515
TI  - Solitary sclerosis: Progressive neurological deficit from a spatially isolated
      demyelinating lesion: A further report.
AB  - CONTEXT: Progressive myelopathy can be a manifestation of a variety of disorders
      including progressive multiple sclerosis. However it is extremely uncommon for a
      single lesion to cause a progressive myelopathy in MS. Such a myelopathy, i.e. a
      progressive neurological deficit from a solitary demyelinating lesion, not
      fulfilling the International diagnostic criteria for MS or Neuromyelitis Optica
      was first reported in 2012 and termed 'solitary sclerosis'. METHOD: We report 3
      further cases of progressive myelopathy fulfilling the diagnostic criteria for
      solitary sclerosis. FINDINGS: Two patients had a single demyelinating lesion in
      the cervical cord and the third patient had it in the brain stem. All patients
      had serial MRI scans showing no dissemination or progression of lesions.
      Extensive diagnostic tests including aquaporin 4 antibodies were negative in all.
      At last follow-up at a median of 3.8 years, all patients continued to clinically
      progress despite immunosuppressive treatment. CONCLUSION/CLINICAL RELEVANCE:
      Solitary demyelinating lesions can cause a progressive myelopathy without
      clinical or radiological evidence of dissemination. Importantly, clinicians, both
      surgical and medical should be aware of such a diagnosis, to avoid invasive and
      often harmful tests particularly biopsies.

PMID- 25615516
TI  - Preliminary evaluation of local drug delivery of amphotericin B and in vivo
      degradation of chitosan and polyethylene glycol blended sponges.
AB  - This research investigated the combination of polyethylene glycol with chitosan
      in point-of-care loaded sponges made by one or two lyophilizations for adjunctive
      local antifungal delivery in musculoskeletal wounds. Blended and control chitosan
      sponges were evaluated in vitro for antifungal release and activity, degradation,
      cytocompatibility, and characterized for spectroscopic, crystallinity, thermal,
      and morphologic material properties. In vivo biocompatibility and degradation of
      sponges were also evaluated in a rat intramuscular pouch model 4 and 10 days
      after implantation. Blended sponges released amphotericin B active against
      Candida albicans (>0.25 ug/mL) over 72 h and did not elicit cytotoxicity response
      of fibroblasts. Blended sponges exhibited decreases in surface roughness,
      decreased thermal decomposition temperatures, as well as small Fourier transform
      infrared spectroscopy and crystallinity differences, compared with chitosan-only
      sponges. Three of the four blended sponge formulations exhibited 31%-94%
      increases in in vitro degradation from the chitosan sponges after 10 days, but
      did not demonstrate the same increase in in vivo degradation. Low inflammatory in
      vivo tissue response to blended and chitosan-only sponges was similar over 10
      days. These results demonstrated that adding polyethylene glycol to chitosan
      sponges does improve local antifungal release, cytocompatibility, and in vitro
      degradation, but does not increase in vivo degradation.

PMID- 25615521
TI  - Critical predicted no effect concentrations (PNECs) should not be based on a
      single toxicity test.
AB  - Predicted no-effect concentrations (PNECs), which represent the concentration of
      a substance below which an unacceptable effect most likely will not occur, are
      widely used for risk assessment and in environmental policy and regulation. They
      are typically based on single-species laboratory toxicity tests; often, a single
      test result for the most sensitive endpoints drives the derivation of a PNEC. In
      the present study, the authors provide a case study emphasizing the importance of
      determining the reliability of those most sensitive endpoints. Five 21-d Daphnia
      magna toxicity tests conducted using the same procedures by 2 laboratories gave
      20% inhibitory concentration responses to a specific ionic composition of total
      dissolved solids that varied from 684 mg/L to more than 1510 mg/L. The
      concentration-response curve was shallow; thus, these differences could have been
      attributable to chance alone. The authors strongly recommend that the most
      sensitive endpoints that determine PNECs not be based on a single toxicity test
      result but rather on the geometric mean of at least 3 test results to adequately
      assess and bound test variability, especially when the concentration-response
      curve is shallow.

PMID- 25615522
TI  - Classification of potato cultivars to establish their processing aptitude.
AB  - BACKGROUND: The commercial potato cultivars are diverse not only in their
      physical characteristics but also in their nutritional compositions and their
      content of functional compounds (resistant starch, total phenolic content and
      antioxidant activity), but there is little information about these differences.
      The aim of this study was to characterise the nutritional value (focusing on
      carbohydrates and functional compounds) and instrumental parameters of eight
      potato cultivars consumed in Spain and to determine whether these parameters are
      useful for classifying the cultivars. RESULTS: Significant Pearson's correlations
      were found due to the common and complex interactions between the constituents of
      potatoes and their properties (P < 0.05). Principal component analysis revealed
      the correlations among the physicochemical properties, and the first two
      principal components explained 56.84% of the variance among the cultivars
      studied. CONCLUSION: The eight cultivars could be classified into three groups:
      (1) Red Pontiac, Caesar, Kennebec, Agria and Cherie cultivars, (2) Agata and
      Monalisa cultivars and (3) Spirit cultivar. The results demonstrated that certain
      nutritional and functional parameters indicated the potential efficacy of
      different cultivars to satisfy the nutritional needs of consumers, improving the
      knowledge on the biochemical basis of potato processing to obtain higher-quality
      products.

PMID- 25615523
TI  - The impact of alcohol use severity on anxiety treatment outcomes in a large
      effectiveness trial in primary care.
AB  - OBJECTIVE: The presence of anxiety disorders is associated with poorer alcohol
      use disorder treatment outcomes, but little is known about the impact of alcohol
      use problems on anxiety disorder treatment outcomes despite their high
      comorbidity. The current study examined the impact of alcohol use symptom
      severity on anxiety disorder treatment outcomes in a multi-site primary care
      effectiveness study of anxiety disorder treatment. METHOD: Data came from the
      Coordinated Anxiety Learning and Management (CALM) effectiveness trial.
      Participants (N=1004) were randomized to an evidence-based anxiety intervention
      (including cognitive behavioral therapy and medications) or usual care in primary
      care. Participants completed measures of alcohol use, anxiety, and depression at
      baseline, 6-, 12-, and 18-month follow-up periods. Patients with alcohol
      dependence were excluded. RESULTS: There were no significant moderating
      (Treatment Group * Alcohol Use Severity) interactions. The majority of analyses
      revealed no predictive effects of alcohol use severity on outcome; however,
      alcohol problems at baseline were associated with somewhat higher anxiety and
      depression symptoms at the 18-month follow-up. CONCLUSIONS: These data indicate
      that patients with alcohol problems in primary care can be effectively treated
      for anxiety disorders. Baseline alcohol problems were associated with some poorer
      long-term outcomes, but this was evident across CALM and usual care. These
      findings provide preliminary evidence that there may be no need to postpone
      treatment of anxiety disorders until alcohol problems are addressed, at least
      among those who have mild to moderate alcohol problems. Replication with more
      severe alcohol use disorders is needed.

PMID- 25615524
TI  - Comments on the elevated IL-27 expression in neonates: relevance between
      detecting nucleotide sequence or protein synthesized.

PMID- 25615525
TI  - Interpretation of pH-activity profiles for acid-base catalysis from molecular
      simulations.
AB  - The measurement of reaction rate as a function of pH provides essential
      information about mechanism. These rates are sensitive to the pK(a) values of
      amino acids directly involved in catalysis that are often shifted by the enzyme
      active site environment. Experimentally observed pH-rate profiles are usually
      interpreted using simple kinetic models that allow estimation of "apparent pK(a)"
      values of presumed general acid and base catalysts. One of the underlying
      assumptions in these models is that the protonation states are uncorrelated. In
      this work, we introduce the use of constant pH molecular dynamics simulations in
      explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a
      tool to aid in the interpretation of pH-activity data of enzymes and to test the
      validity of different kinetic models. We apply the methods to RNase A, a
      prototype acid-base catalyst, to predict the macroscopic and microscopic pK(a)
      values, as well as the shape of the pH-rate profile. Results for apo and cCMP
      bound RNase A agree well with available experimental data and suggest that
      deprotonation of the general acid and protonation of the general base are not
      strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling,
      however, is predicted for the Lys41 and His119 protonation states in apo RNase A,
      leading to the requirement for a microscopic kinetic model. This type of analysis
      may be important for other catalytic systems where the active forms of the
      implicated general acid and base are oppositely charged and more highly
      correlated. These results suggest a new way for CpHMD/pH-REMD simulations to
      bridge the gap with experiments to provide a molecular-level interpretation of pH
      activity data in studies of enzyme mechanisms.

PMID- 25615527
TI  - Do we need a practice incremental shuttle walk test for patients with
      interstitial lung disease referred for pulmonary rehabilitation?
AB  - BACKGROUND AND OBJECTIVE: Patients with interstitial lung disease (ILD) are
      increasingly being referred to pulmonary rehabilitation (PR) where exercise
      capacity is measured, often by an incremental shuttle walk test (ISWT). These
      patients are frequently limited by severe dyspnoea and exertional desaturation.
      Available guidelines suggest two ISWT are needed; however, this is time consuming
      and it has not been reported whether a practice ISWT is necessary in ILD. We
      aimed to investigate if a practice ISWT is needed for patients with ILD referred
      to PR. METHODS: Patients with ILD who attended a PR assessment performed two ISWT
      as per standard protocol. Hospital notes were retrieved and relevant data
      extracted and validated. Endurance shuttle walk test (ESWT) level was calculated
      at 85% VO2 peak as estimated from the first ISWT (ISWT 1) and second ISWT (ISWT
      2). RESULTS: Forty-three patients were included (18 with idiopathic pulmonary
      fibrosis). There was a mean change of 28.84 (31.71) m between the two ISWT (P <
      0.001) with 72.1% of patients walking further on ISWT 2. A Bland-Altman plot
      showed good agreement between the ISWTs; however, the limits of agreement were
      wide. There was a significant difference in ESWT levels (P < 0.001) when
      calculated from ISWT 1 and ISWT 2. ISWT 1 distance, post-ISWT 1 heart rate and
      baseline Borg breathlessness score were significant variables (P < 0.05) in
      linear regression, but this only explained 42.6% of the variance (R(2) 0.426).
      CONCLUSIONS: A practice ISWT is necessary to accurately assess exercise capacity.
      It was not possible to predict which patients did not need to complete two ISWT.

PMID- 25615526
TI  - UCHL1 provides diagnostic and antimetastatic strategies due to its
      deubiquitinating effect on HIF-1alpha.
AB  - Hypoxia-inducible factor 1 (HIF-1) plays a role in tumour metastases; however,
      the genes that activate HIF-1 and subsequently promote metastases have yet to be
      identified. Here we show that Ubiquitin C-terminal hydrolase-L1 (UCHL1) abrogates
      the von Hippel-Lindau-mediated ubiquitination of HIF-1alpha, the regulatory
      subunit of HIF-1, and consequently promotes metastasis. The aberrant
      overexpression of UCHL1 facilitates distant tumour metastases in a HIF-1
      dependent manner in murine models of pulmonary metastasis. Meanwhile, blockade of
      the UCHL1-HIF-1 axis suppresses the formation of metastatic tumours. The
      expression levels of UCHL1 correlate with those of HIF-1alpha and are strongly
      associated with the poor prognosis of breast and lung cancer patients. These
      results indicate that UCHL1 promotes metastases as a deubiquitinating enzyme for
      HIF-1alpha, which justifies exploiting it as a prognostic marker and therapeutic
      target of cancers. 

PMID- 25615528
TI  - A comprehensive review on the colorless carotenoids phytoene and phytofluene.
AB  - Carotenoids and their derivatives are versatile isoprenoids involved in many
      varied actions, hence their importance in the agri-food industry, nutrition,
      health and other fields. All carotenoids are derived from the colorless carotenes
      phytoene and phytofluene, which are oddities among carotenoids due to their
      distinct chemical structure. They occur together with lycopene in tomato and
      other lycopene-containing foods. Furthermore, they are also present in frequently
      consumed products like oranges and carrots, among others. The intake of phytoene
      plus phytofluene has been shown to be higher than that of lycopene and other
      carotenoids in Luxembourg. This is likely to be common in other countries.
      However, they are not included in food carotenoid databases, hence they have not
      been linked to health benefits in epidemiological studies. Interestingly, there
      are evidences in vitro, animal models and humans indicating that they may provide
      health benefits. In this sense, the study of these colorless carotenes in the
      context of food science, nutrition and health should be further encouraged. In
      this work, we review much of the existing knowledge concerning their chemical
      characteristics, physico-chemical properties, analysis, distribution in foods,
      bioavailability and likely biological activities.

PMID- 25615529
TI  - How our bodies fight amyloidosis: effects of physiological factors on pathogenic
      aggregation of amyloidogenic proteins.
AB  - The process of protein aggregation from soluble amyloidogenic proteins to
      insoluble amyloid fibrils plays significant roles in the onset of over 30 human
      amyloidogenic diseases, such as Prion disease, Alzheimer's disease and type 2
      diabetes mellitus. Amyloid deposits are commonly found in patients suffered from
      amyloidosis; however, such deposits are rarely seen in healthy individuals, which
      may be largely attributed to the self-regulation in vivo. A vast number of
      physiological factors have been demonstrated to directly affect the process of
      amyloid formation in vivo. In this review, physiological factors that influence
      amyloidosis, including biological factors (chaperones, natural antibodies,
      enzymes, lipids and saccharides) and physicochemical factors (metal ions, pH
      environment, crowding and pressure, etc.), together with the mechanisms
      underlying these proteostasis effects, are summarized.

PMID- 25615530
TI  - Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked
      Oligosaccharides in the Golgi Apparatus.
AB  - The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune
      modulatory receptor involved in phagocytosis and inflammation. Mutations of Q33X,
      Y38C and T66M cause Nasu-Hakola disease (NHD) which is characterized by early
      onset of dementia and bone cysts. A recent, genome-wide association study also
      revealed that single nucleotide polymorphism of TREM2, such as R47H, increased
      the risk of Alzheimer's disease (AD) similar to ApoE4. However, how these
      mutations affect the trafficking of TREM2, which may affect the normal functions
      of TREM2, was not known. In this study, we show that TREM2 with NHD mutations are
      impaired in the glycosylation with complex oligosaccharides in the Golgi
      apparatus, in the trafficking to plasma membrane and further processing by gamma
      secretase. Although R47H mutation in AD affected the glycosylation and normal
      trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs
      from that of the wild type, thus suggesting that precise regulation of TREM2
      glycosylation is impaired when arginine at 47 is mutated to histidine. Our
      results suggest that the impaired glycosylation and trafficking of TREM2 from
      endoplasmic reticulum/Golgi to plasma membrane by mutations may inhibit its
      normal functions in the plasma membrane, which may contribute to the disease. 

PMID- 25615531
TI  - Chemistry and diversity of pyridoxal-5'-phosphate dependent enzymes.
AB  - Pyridoxal-5'-phosphate (PLP) is a versatile cofactor that enzymes use to catalyze
      a wide variety of reactions of amino acids, including transamination,
      decarboxylation, racemization, beta- and gamma-eliminations and substitutions,
      retro-aldol and Claisen reactions. These reactions depend on the ability of PLP
      to stabilize, to a varying degree, alpha-carbanionic intermediates. Furthermore,
      oxidative decarboxylations and rearrangements suggest that PLP can stabilize
      radical intermediates as well. The reaction mechanisms of two PLP-dependent
      enzymes are discussed, kynureninase and tyrosine phenol-lyase (TPL). Kynureninase
      catalyzes a retro-Claisen reaction of kynurenine to give anthranilate and
      alanine. The key step, hydration of the gamma-carbonyl, is assisted by acid-base
      catalysis with the phosphate of the PLP, mediated by a conserved tyrosine, and an
      oxyanion hole. TPL catalyzes the reversible elimination of phenol, a poor leaving
      group, from l-tyrosine. In TPL, the Cbeta-Cgamma bond cleavage is accelerated by
      ground state strain from the bending of the substrate ring out of the plane with
      the Cbeta-Cgamma bond. This article is part of a Special Issue entitled: Cofactor
      dependent proteins: evolution, chemical diversity and bio-applications. 

PMID- 25615532
TI  - Horizontal transmission of an R4 clade non-long terminal repeat retrotransposon
      between the divergent Aedes and Anopheles mosquito genera.
AB  - AaegR4_1 and AgamR4_1 are the sole R4 clade non-long terminal repeat (non-LTR)
      retrotransposons in Aedes aegypti and Anopheles gambiae, two species that
      diverged approximately 145-200 million years ago. Twelve full-length copies were
      found in Ae. aegypti and have less than 1% nucleotide (nt) divergence, suggesting
      recent activity on an evolutionary time scale. Five of these copies have intact
      open reading frames and the 3.6 kb open reading frame of AaegR4_1.1 has 78% nt
      identity to AgamR4_1.1. No intact copies were found in An. gambiae. Searches of
      25 genomic databases for 22 mosquito species from three genera revealed R4 clade
      representatives in Aedes and Anopheles genera but not in Culex. Interestingly,
      these elements are present in all six species of the An. gambiae species complex
      that were searched but not in 13 other anopheline species. These results combined
      with divergence vs. age analysis suggest that horizontal transfer is the most
      likely explanation for the low divergence between R4 clade retrotransposon
      sequences of the divergent mosquito species from the Aedes and Anopheles genera.
      This is the first report of the horizontal transfer of an R4 clade non-LTR
      retrotransposon and the first report of the horizontal transfer of a non-LTR
      retrotransposon in mosquitoes. 

PMID- 25615533
TI  - Toxicity screening of diclofenac, propranolol, sertraline and simvastatin using
      Danio rerio and Paracentrotus lividus embryo bioassays.
AB  - Early life-stage bioassays have been used as an alternative to short-term adult
      toxicity tests since they are cost-effective. A single couple can produce
      hundreds or thousands of embryos and hence can be used as a simple high
      throughput approach in toxicity studies. In the present study, zebrafish and sea
      urchin embryo bioassays were used to test the toxicity of four pharmaceuticals
      belonging to different therapeutic classes: diclofenac, propranolol, simvastatin
      and sertraline. Simvastatin was the most toxic tested compound for zebrafish
      embryo, followed by diclofenac. Sertraline was the most toxic drug to sea urchin
      embryos, inducing development abnormalities at the ng/L range. Overall, our
      results highlight the potential of sea urchin embryo bioassay as a promising and
      sensitive approach for the high-throughput methods to test the toxicity of new
      chemicals, including pharmaceuticals, and identify several drugs that should go
      through more detailed toxicity assays. 

PMID- 25615534
TI  - Bladder cancer mortality after spinal cord injury over 4 decades.
AB  - PURPOSE: We estimate bladder cancer mortality in people with spinal cord injury
      compared to the general population. MATERIALS AND METHODS: Data and statistics
      were retrieved from the National Spinal Cord Injury Statistical Center and the
      National Center for Health Statistics. The mortality experience of the 45,486
      patients with traumatic spinal cord injury treated at a Spinal Cord Injury Model
      System or Shriners Hospital was compared to the general population using a
      standardized mortality ratio. The standardized mortality ratio data were further
      stratified by age, gender, race, time since injury and injury severity. RESULTS:
      Our study included 566,532 person-years of followup between 1960 and 2009,
      identified 10,575 deaths and categorized 99 deaths from bladder cancer. The
      expected number of deaths from bladder cancer would have been 14.8 if patients
      with spinal cord injury had the same bladder cancer mortality as the general
      population. Thus, the standardized mortality ratio is 6.7 (95% CI 5.4-8.1).
      Increased mortality risk from bladder cancer was observed for various ages, races
      and genders, as well as for those injured for 10 or more years and with motor
      complete injuries. Bladder cancer mortality was not significantly increased for
      ventilator users, those with motor incomplete injuries or those injured less than
      10 years. CONCLUSIONS: Individuals with a spinal cord injury can potentially live
      healthier and longer by reducing the incidence and mortality of bladder cancer.
      Study findings highlight the need to identify at risk groups and contributing
      factors for bladder cancer death, leading to the development of prevention,
      screening and management strategies.

PMID- 25615536
TI  - Editorial preface.

PMID- 25615535
TI  - The Nav1.2 channel is regulated by GSK3.
AB  - BACKGROUND: Phosphorylation plays an essential role in regulating voltage-gated
      sodium (Na(v)) channels and excitability. Yet, a surprisingly limited number of
      kinases have been identified as regulators of Na(v) channels. We posited that
      glycogen synthase kinase 3 (GSK3), a critical kinase found associated with
      numerous brain disorders, might directly regulate neuronal Na(v) channels.
      METHODS: We used patch-clamp electrophysiology to record sodium currents from
      Na(v)1.2 channels stably expressed in HEK-293 cells. mRNA and protein levels were
      quantified with RT-PCR, Western blot, or confocal microscopy, and in vitro
      phosphorylation and mass spectrometry to identify phosphorylated residues.
      RESULTS: We found that exposure of cells to GSK3 inhibitor XIII significantly
      potentiates the peak current density of Na(v)1.2, a phenotype reproduced by
      silencing GSK3 with siRNA. Contrarily, overexpression of GSK3beta suppressed
      Na(v)1.2-encoded currents. Neither mRNA nor total protein expression was changed
      upon GSK3 inhibition. Cell surface labeling of CD4-chimeric constructs expressing
      intracellular domains of the Na(v)1.2 channel indicates that cell surface
      expression of CD4-Na(v)1.2 C-tail was up-regulated upon pharmacological
      inhibition of GSK3, resulting in an increase of surface puncta at the plasma
      membrane. Finally, using in vitro phosphorylation in combination with high
      resolution mass spectrometry, we further demonstrate that GSK3beta phosphorylates
      T(1966) at the C-terminal tail of Na(v)1.2. CONCLUSION: These findings provide
      evidence for a new mechanism by which GSK3 modulates Na(v) channel function via
      its C-terminal tail. GENERAL SIGNIFICANCE: These findings provide fundamental
      knowledge in understanding signaling dysfunction common in several
      neuropsychiatric disorders.

PMID- 25615537
TI  - FKBPs and their role in neuronal signaling.
AB  - BACKGROUND: Ligands for FK506-binding proteins, also referred to as
      neuroimmunophilin ligands, have repeatedly been described as neuritotrophic,
      neuroprotective or neuroregenerative agents. However, the precise molecular
      mechanism of action underlying the observed effects has remained elusive, which
      eventually led to a reduced interest in FKBP ligand development. SCOPE OF REVIEW:
      A survey is presented on the pharmacology of neuroimmunophilin ligands, of the
      current understanding of individual FKBP homologs in neuronal processes and an
      assessment of their potential as drug targets for CNS disorders. MAJOR
      CONCLUSIONS: FKBP51 is the major target accounting for the neuritotrophic effect
      of neuroimmunophilin ligands. Selectivity against the homolog FKBP52 is essential
      for optimal neuritotrophic efficacy. GENERAL SIGNIFICANCE: Selectivity within the
      FKBP family, in particular selective inhibition of FKBP12 or FKBP51, is possible.
      FKBP51 is a pharmacologically tractable target for stress-related disorders. The
      role of FKBPs in neurodegeneration remains to be clarified. This article is part
      of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts
      and Drug Targets.

PMID- 25615539
TI  - Prior attenuation of KiSS1/GPR54 signaling in the anteroventral periventricular
      nucleus is a trigger for the delayed effect induced by neonatal exposure to
      17alpha-ethynylestradiol in female rats.
AB  - Neonatal exposure to 17alpha-ethynylestradiol (EE) causes delayed effect, a late
      occurring irreversible damage to reproductive functions characterized by the
      early onset of age-matched abnormal estrous cycling. To clarify the involvement
      of a hypothalamic key cycling regulator KiSS1/GPR54 in the delayed effect, we
      investigated artificially induced LH surges and KiSS1 mRNA expression in the
      anteroventral periventricular nucleus (AVPV) of cycling young adult rats
      neonatally exposed to EE, and compared these parameters to those in about 5
      months old middle-aged rats. KiSS1 mRNA expression, the number of KiSS1-positive
      cells and KiSS1/ERalpha co-expressing cells in the AVPV decreased in both EE
      exposed and middle-aged rats. The peak area and levels of LH surge dose
      dependently decreased in EE-exposed rats, and reduction was more evident in
      middle-aged rats. These results indicate that the prior attenuation of KiSS1 and
      consequent depression of LH surges plays a key role in the onset of abnormal
      estrous cycling in the delayed effect. 

PMID- 25615538
TI  - Effects of defeat stress on behavioral flexibility in males and females:
      modulation by the mu-opioid receptor.
AB  - Behavioral flexibility is a component of executive functioning that allows
      individuals to adapt to changing environmental conditions. Independent lines of
      research indicate that the mu opioid receptor (MOR) is an important mediator of
      behavioral flexibility and responses to psychosocial stress. The current study
      bridges these two lines of research and tests the extent to which social defeat
      and MOR affect behavioral flexibility and whether sex moderates these effects in
      California mice (Peromyscus californicus). Males and females assigned to social
      defeat or control conditions were tested in a Barnes maze. In males, defeat
      impaired behavioral flexibility but not acquisition. Female performance was
      unaffected by defeat. MOR binding in defeated and control mice in the
      orbitofrontal cortex (OFC), striatum and hippocampus was examined via
      autoradiography. Stressed males had reduced MOR binding in the OFC whereas
      females were unaffected. The MOR antagonist beta-funaltrexamine (1 mg/kg)
      impaired performance in males naive to defeat during the reversal phase but had
      no effect on females. Finally, we examined the effects of the MOR agonist
      morphine (2.5 and 5 mg/kg) on stressed mice. As expected, morphine improved
      behavioral flexibility in stressed males. The stress-induced deficits in
      behavioral flexibility in males are consistent with a proactive coping strategy,
      including previous observations that stressed male California mice exhibit strong
      social approach and aggression. Our pharmacological data suggest that a down
      regulation of MOR signaling in males may contribute to sex differences in
      behavioral flexibility following stress. This is discussed in the framework of
      coping strategies for individuals with mood disorders.

PMID- 25615541
TI  - Multiarylpolycarboxylate-mediated hybrid cobalt phosphate frameworks with
      supramolecular zeolitic topology and unusual I(2)O(2) connectivity.
AB  - Two novel organic-inorganic hybrid frameworks containing multiarylpolycarboxylate
      linkers and cobalt phosphate layers, [H2DABCO].[Co(HPO4)(bpdc)] (1) and
      [H2DABCO]3.[Co10(npa)3(PO4)6Cl2] (2), where bpdc = 4,4'-biphenyldicarboxylate,
      npa = 2,6-naphthalenedicarboxylate, and DABCO = 1,4-diazabicyclo[2.2.2]octane,
      have been solvothermally synthesized. Compound 1 features a 3D zeolite-like
      supramolecular network with ABW topology, and compound 2 is a 3D framework
      structure with unusual I(2)O(2) connectivity. 

PMID- 25615540
TI  - Prefrontal NMDA receptors expressed in excitatory neurons control fear
      discrimination and fear extinction.
AB  - N-methyl-D-aspartate receptors (NMDARs) are critically involved in various
      learning mechanisms including modulation of fear memory, brain development and
      brain disorders. While NMDARs mediate opposite effects on medial prefrontal
      cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger
      profound cortical activation. The objectives of the present study were to
      determine the involvement of NMDARs expressed specifically in excitatory neurons
      in mPFC-dependent adaptive behaviors, specifically fear discrimination and fear
      extinction. To achieve this, we tested mice with locally deleted Grin1 gene
      encoding the obligatory NR1 subunit of the NMDAR from prefrontal CamKIIalpha
      positive neurons for their ability to distinguish frequency modulated (FM) tones
      in fear discrimination test. We demonstrated that NMDAR-dependent signaling in
      the mPFC is critical for effective fear discrimination following initial
      generalization of conditioned fear. While mice with deficient NMDARs in
      prefrontal excitatory neurons maintain normal responses to a dangerous fear
      conditioned stimulus, they exhibit abnormal generalization decrement. These
      studies provide evidence that NMDAR-dependent neural signaling in the mPFC is a
      component of a neural mechanism for disambiguating the meaning of fear signals
      and supports discriminative fear learning by retaining proper gating information,
      viz. both dangerous and harmless cues. We also found that selective deletion of
      NMDARs from excitatory neurons in the mPFC leads to a deficit in fear extinction
      of auditory conditioned stimuli. These studies suggest that prefrontal NMDARs
      expressed in excitatory neurons are involved in adaptive behavior. 

PMID- 25615542
TI  - Dynamic assessment of morphological awareness and third-grade literacy success.
AB  - PURPOSE: The purpose of this study was to examine a dynamic assessment with
      graduated prompts to assess morphological awareness and determine whether such a
      task was related to third-grade literacy success. METHOD: A dynamic assessment of
      morphological awareness was adapted and administered to 54 third-grade students
      in addition to a norm-referenced language and literacy battery. RESULTS: A
      dynamic assessment of morphological awareness measured a range of performance
      including that of emerging morphological awareness abilities and provided rich
      linguistic insights for how best to scaffold and prompt for such a skill. In
      addition, the dynamic morphological awareness measure was found to be
      significantly related to, and to contribute unique variance to, reading
      comprehension abilities. CONCLUSIONS: These results suggest that morphological
      awareness is an important factor to consider when addressing students' literacy
      performance in early elementary school and that dynamic assessment appears to be
      a clinically valuable tool when examining early morphological awareness
      abilities.

PMID- 25615544
TI  - Mucous membrane pemphigoid with esophageal stricture treated with balloon
      dilatation.

PMID- 25615543
TI  - Studies on cocktails of 31-kDa, 36-kDa and 51-kDa antigens of Leishmania donovani
      along with saponin against murine visceral leishmaniasis.
AB  - A substantial number of antigens of Leishmania donovani have been described in
      the past. However, identifying candidate antigens is not enough. Appropriate
      antigen delivery to induce the right type of immune response against
      leishmaniasis (i.e. induction of a strong antigen-specific Th1 type of immune
      response) is another crucial component of an effective vaccine. Therefore,
      'cocktail' vaccines are proposed based on the assumption that such cocktails will
      show enhanced efficacy. Studies have been carried out on LD31 and LD51
      polypeptides from L. donovani promastigotes, which have proven to be potential
      vaccine candidates. This study was designed to check the protective efficacy of
      various cocktails of low molecular weight antigens alone and along with saponin
      as adjuvant. Mice were sacrificed on different post-challenge days for evaluation
      of parasite load and other immunological parameters. Protective efficacy of
      different vaccine formulations was revealed by significant decline in parasite
      burden and increased DTH Delayed Type Hypersenstivity responses. The antibody
      response was of IgG type with elevated IgG2a and decreased production of IgG1,
      whereas cytokine levels pointed towards the generation of protective Th1 type of
      immune response. Among all vaccine formulations, cocktail of 31+51+saponin was
      found to be highly immunogenic and imparted maximum protection. 

PMID- 25615545
TI  - Development and maintenance of force and stiffness in airway smooth muscle.
AB  - Airway smooth muscle (ASM) plays a central role in the excessive narrowing of the
      airway that characterizes the primary functional impairment in asthma. This
      phenomenon is known as airway hyper-responsiveness (AHR). Emerging evidence
      suggests that the development and maintenance of ASM force involves dynamic
      reorganization of the subcellular filament network in both the cytoskeleton and
      the contractile apparatus. In this review, evidence is presented to support the
      view that regulation of ASM contraction extends beyond the classical actomyosin
      interaction and involves processes within the cytoskeleton and at the interfaces
      between the cytoskeleton, the contractile apparatus, and the extracellular
      matrix. These processes are initiated when the muscle is activated, and
      collectively they cause the cytoskeleton and the contractile apparatus to undergo
      structural transformation, resulting in a more connected and solid state that
      allows force generated by the contractile apparatus to be transmitted to the
      extracellular domain. Solidification of the cytoskeleton also serves to stiffen
      the muscle and hence the airway. Oscillatory strain from tidal breathing and deep
      inspiration is believed to be the counter balance that prevents hypercontraction
      and stiffening of ASM in vivo. Dysregulation of this balance could lead to AHR
      seen in asthma. 

PMID- 25615547
TI  - Robust microzip fastener: repeatable interlocking using polymeric rectangular
      parallelepiped arrays.
AB  - We report a highly repeatable and robust microzip fastener based on the van der
      Waals force-assisted interlocking between rectangular parallelepiped arrays. To
      investigate zipperlike interlocking behaviors, various line arrays were
      fabricated with three different spacing ratios (1, 3, and 5 of 800 nm in width)
      and width of parallelepipeds (400 nm, 800 nm, and 5 MUm with the spacing ratio of
      1). In addition, the different rigidity of line arrays was inspected for a
      repeatable microzip fastener. The normal and shear locking forces were measured
      with variation of the material rigidity as well as geometry of the array, in good
      agreement with a proposed theory based on the contact area and force balance. The
      maximum adhesion forces as high as ~8.5 N cm(-2) in the normal direction and
      ~29.6 N cm(-2) in the shear direction were obtained with high stability up to
      1000 cycles. High stability of our fastening system was confirmed for preventing
      critical failures such as buckling and fracture in practical applications. 

PMID- 25615548
TI  - Does language learning disability in school-age children affect semantic word
      learning when reading?
AB  - PURPOSE: The study was undertaken to determine how position of informative
      context, rate of word presentation and part of speech impacted novel word
      learning during reading in children with language learning disability. METHOD:
      Children with language learning disability (LLD; n = 13), age-matched peers (n =
      13) and vocabulary-matched peers (n = 13) read four narrative passages containing
      10 nouns and 10 verbs. Informative context provided clues to word meanings and
      was either adjacent or non-adjacent to the target words. Target words occurred
      either twice (low rate) or 5-times (high rate). Following reading, word learning
      was assessed using dynamic assessment, including oral definitions, contextual
      clues and forced choices. RESULT: Overall, age-matched peers performed better
      than children with LLD and vocabulary-matched peers, who performed similarly. No
      effect was found for position of informative context; however, word learning
      improved with high rate of presentation for children with LLD. Nouns were easier
      to learn than verbs for all groups. CONCLUSION: Results indicated that children
      with LLD show limitations gaining semantic knowledge of novel words during
      reading, which could negatively impact their overall rate of vocabulary
      acquisition.

PMID- 25615546
TI  - Factors regulating immunoglobulin production by normal and disease-associated
      plasma cells.
AB  - Immunoglobulins are molecules produced by activated B cells and plasma cells in
      response to exposure to antigens. Upon antigen exposure, these molecules are
      secreted allowing the immune system to recognize and effectively respond to a
      myriad of pathogens. Immunoglobulin or antibody secreting cells are the mature
      form of B lymphocytes, which during their development undergo gene rearrangements
      and selection in the bone marrow ultimately leading to the generation of B cells,
      each expressing a single antigen-specific receptor/immunoglobulin molecule. Each
      individual immunoglobulin molecule has an affinity for a unique motif, or
      epitope, found on a given antigen. When presented with an antigen, activated B
      cells differentiate into either plasma cells (which secrete large amounts of
      antibody that is specific for the inducing antigen), or memory B cells (which are
      long-lived and elicit a stronger and faster response if the host is re-exposed to
      the same antigen). The secreted form of immunoglobulin, when bound to an antigen,
      serves as an effector molecule that directs other cells of the immune system to
      facilitate the neutralization of soluble antigen or the eradication of the
      antigen-expressing pathogen. This review will focus on the regulation of secreted
      immunoglobulin by long-lived normal or disease-associated plasma. Specifically,
      the focus will be on signaling and transcriptional events that regulate the
      development and homeostasis of long-lived immunoglobulin secreting plasma cells. 

PMID- 25615549
TI  - Occupational therapy with people with depression: using nominal group technique
      to collate clinician opinion.
AB  - AIMS: This aim of this study was to obtain a consensus from clinicians regarding
      occupational therapy for people with depression, for the assessments and
      practices they use that are not currently supported by research evidence directly
      related to functional performance. The study also aimed to discover how many of
      these assessments and practices were currently supported by research evidence.
      METHODS: Following a previously reported systematic review of assessments and
      practices used in occupational therapy for people with depression, a modified
      nominal group technique was used to discover which assessments and practices
      occupational therapists currently utilize. Three online surveys gathered initial
      data on therapeutic options (survey 1), which were then ranked (survey 2) and re
      ranked (survey 3) to gain the final consensus. Twelve therapists completed the
      first survey, whilst 10 clinicians completed both the second and third surveys.
      MAJOR FINDINGS: Only 30% of the assessments and practices identified by the
      clinicians were supported by research evidence. A consensus was obtained on a
      total of 35 other assessments and interventions. These included both occupational
      therapy-specific and generic assessments and interventions. Principle conclusion.
      Very few of the assessments and interventions identified were supported by
      research evidence directly related to functional performance. While a large
      number of options were generated, the majority of these were not occupational
      therapy specific.

PMID- 25615550
TI  - Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile
      of ABCC6 and ENPP1 mutations.
AB  - Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by
      ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined
      clinically 29 Chinese PXE patients from unrelated families, so far the largest
      cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and
      another candidate gene, ENPP1, and conducted pathogenicity analyses for each
      variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them
      being, to our knowledge, previously unreported, including 5 frameshift and 10
      missense variants. In addition, a missense mutation in combination with a
      recurrent nonsense mutation in ENPP1 was discovered in a pediatric PXE case. No
      cases with p.R1141X or del23-29 mutations, common in Caucasian patient
      populations, were identified. The 10 missense mutations in ABCC6 were expressed
      in the mouse liver via hydrodynamic tail-vein injections. One mutant protein
      showed cytoplasmic accumulation indicating abnormal subcellular trafficking,
      while the other nine mutants showed correct plasma membrane location. These nine
      mutations were further investigated for their pathogenicity using a recently
      developed zebrafish mRNA rescue assay. Minimal rescue of the morpholino-induced
      phenotype was achieved with eight of the nine mutant human ABCC6 mRNAs tested,
      implying pathogenicity. This study demonstrates that the Chinese PXE population
      harbors unique ABCC6 mutations. These genetic data have implications for allele
      specific therapy currently being developed for PXE. 

PMID- 25615551
TI  - Development and Validation of a Quality-of-Life Instrument for Infantile
      Hemangiomas.
AB  - Infantile hemangiomas (IH) are common tumors for which there is no validated
      disease-specific instrument to measure the quality of life in infants and their
      parents/caregivers during the critical first months of life. This study
      prospectively developed and validated a quality-of-life instrument for patients
      with IH and their parents/caregivers and correlated demographic and clinical
      features to the effects on the quality of life. A total of 220 parents/caregivers
      completed the 35-item Infantile Hemangioma Quality-of-Life (IH-QoL) instrument
      and provided demographic information. The dimensionality of the items was
      evaluated using factor analysis, with results suggesting four factors: child
      physical symptoms, child social interactions, parent emotional functioning, and
      parent psychosocial functioning. Each factor fit the Rasch measurement model with
      acceptable fit index (mean square <1.4) and demonstrated excellent internal
      consistency, with alpha ranging from 0.76 to 0.88. The final instrument consists
      of four scales with a total of 29 items. Content validity was verified by
      analyzing parents' responses to an open-ended question. Test-retest reliability
      at a 48-hour interval was supported by a total IH-QoL intraclass correlation
      coefficient of 0.84. Certain clinical characteristics of hemangioma, including
      those located on the head and neck, in the proliferative stage, and requiring
      treatment, are associated with a greater impact on QoL. 

PMID- 25615552
TI  - The role of eIF4E in response and acquired resistance to vemurafenib in melanoma.
AB  - In eukaryotic cells, the rate-limiting component for cap-dependent mRNA
      translation is the translation initiation factor eIF4E. eIF4E is overexpressed in
      a variety of human malignancies, but whether it has a role in melanoma remains
      obscure. We hypothesized that eIF4E promotes melanoma cell proliferation and
      facilitates the development of acquired resistance to the BRAF inhibitor
      vemurafenib. We show that eIF4E is overexpressed in a panel of melanoma cell
      lines, compared with immortalized melanocytes. Knockdown of eIF4E significantly
      repressed the proliferation of a subset of melanoma cell lines. Moreover, in
      BRAF(V600E) melanoma cell lines, vemurafenib inhibits 4E-BP1 phosphorylation,
      thus promoting its binding to eIF4E. Cap-binding and polysome profiling analysis
      confirmed that vemurafenib stabilizes the eIF4E-4E-BP1 association and blocks
      mRNA translation, respectively. Conversely, in cells with acquired resistance to
      vemurafenib, there is an increased dependence on eIF4E for survival; 4E-BP1 is
      highly phosphorylated and thus eIF4E-4E-BP1 associations are impeded. Moreover,
      increasing eIF4E activity by silencing 4E-BP1/2 renders vemurafenib-responsive
      cells more resistant to BRAF inhibition. In conclusion, these data suggest that
      therapeutically targeting eIF4E may be a viable means of inhibiting melanoma cell
      proliferation and overcoming vemurafenib resistance. 

PMID- 25615553
TI  - An autosomal recessive mutation of DSG4 causes monilethrix through the ER stress
      response.
AB  - Monilethrix is a hair shaft anomaly characterized by beaded hair with periodic
      changes in hair thickness. Mutations in the desmoglein 4 (DSG4) gene reportedly
      underlie the autosomal recessive form of the disease. However, the pathogenesis
      and cellular basis for the DSG4 mutation-induced monilethrix remained largely
      unknown. We report a Japanese female patient with monilethrix. Observation of her
      hair shaft by means of transmission electron microscopy showed fewer desmosomes
      and abnormal keratinization. Genetic analysis revealed a homozygous mutation,
      c.2119delG (p.Asp707Ilefs*109), in the DSG4 gene, which was predicted to cause a
      frameshift and premature termination in the intracellular region of the DSG4
      protein. The mutation has not been reported previously. In the patient's hair
      shaft, we detected reduced but partial expression of the mutant DSG4 protein.
      Cellular analyses demonstrated that the mutant DSG4 lost its affinity to
      plakoglobin and accumulated in the endoplasmic reticulum (ER). The amounts of
      mutant DSG4 were increased by proteasome inhibitor treatment, and the expression
      of an ER chaperone, GRP78/BiP, was elevated in the patient's skin. Collectively,
      these results suggest that the dysfunctional mutated DSG4, tethered in the ER,
      undergoes ER-associated degradation, leading to unfolded protein response
      induction, and thus ER stress may have a role in the pathogenesis of monilethrix.

PMID- 25615554
TI  - An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte
      activation.
AB  - In a routine phenotype-driven screen, we identified a point mutation in exon 7 of
      the IL-15 gene in Pedigree 191 (deficient memory (DM)) of N-ethyl-N-nitrosourea
      mutagenized mice. The DM epidermis expressed an alternatively spliced IL-15 mRNA
      isoform, IL-15DeltaE7, and a wild-type (WT) IL-15 isoform at comparable levels.
      Mechanical stimulation of DM skin or DM skin graft transplanted onto the WT host
      resulted in reduced keratinocyte activation and inhibition of neutrophil
      infiltration into the dermis, demonstrating that DM keratinocytes produced less
      inflammatory response to external stimulation. Ectopic expression of IL-15DeltaE7
      in WT skin prevented abrasion-induced epidermal thickening, blocked the
      accumulation of nuclear antigen Ki67(+) cells in the basal and the suprabasal
      cell layers, increased loricrin expression, and also increased keratinocyte CXCL1
      and G-CSF production. IL-15DeltaE7 also profoundly blocked neutrophil
      infiltration in SDS- or immiquimod (IMQ)-treated WT skin. Recombinant IL
      15DeltaE7 failed to activate STAT-5 and its downstream target bcl-2 expression.
      Our study points to IL-15DeltaE7 as a potential therapeutic agent for treating
      neutrophilia-associated inflammatory skin disorders. 

PMID- 25615556
TI  - Highly efficient production of rare sugars D-psicose and L-tagatose by two
      engineered D-tagatose epimerases.
AB  - Rare sugars are monosaccharides that do not occur in nature in large amounts.
      However, many of them demonstrate high potential as low-calorie sweetener, chiral
      building blocks or active pharmaceutical ingredients. Their production by
      enzymatic means from broadly abundant epimers is an attractive alternative to
      synthesis by traditional organic chemical means, but often suffers from low space
      time yields and high enzyme costs due to rapid enzyme degradation. Here we
      describe the detailed characterization of two variants of d-tagatose epimerase
      under operational conditions that were engineered for high stability and high
      catalytic activity towards the epimerization of d-fructose to d-psicose and l
      sorbose to l-tagatose, respectively. A variant optimized for the production of d
      psicose showed a very high total turnover number (TTN) of up to 10(8) catalytic
      events over a catalyst's lifetime, determined under operational conditions at
      high temperatures in an enzyme-membrane reactor (EMR). Maximum space-time yields
      as high as 10.6 kg L(-1) d(-1) were obtained with a small laboratory-scale EMR,
      indicating excellent performance. A variant optimized for the production of l
      tagatose performed less stable in the same setting, but still showed a very good
      TTN of 5.8 * 10(5) and space-time yields of up to 478 g L(-1) d(-1) . Together,
      these results confirm that large-scale enzymatic access to rare sugars is
      feasible.

PMID- 25615555
TI  - Child maltreatment in DSM-5 and ICD-11.
AB  - Child maltreatment is widespread and has a tremendous impact on child victims and
      their families. Over the past decade, definitions of child maltreatment have been
      developed that are operationalized, face valid, and can be reliably applied in
      clinical settings. These definitions have informed the revised Diagnostic and
      Statistical Manual (American Psychiatric Association, 2013) and are being
      considered for the International Classification of Disease-11 (World Health
      Organization). Now that these definitions are available in major diagnostic
      systems, primary healthcare providers and clinicians who see children and
      families are poised to help screen for, identify, prevent, and treat child
      maltreatment. This article reviews the definitions of maltreatment in these
      diagnostic systems, along with assessment and screening tools, and empirically
      supported prevention and intervention approaches. 

PMID- 25615557
TI  - The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy
      and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular
      carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.
AB  - Vibrational signatures of human breast tissue (invasive ductal carcinoma and
      invasive lobular carcinoma) were used to identify, characterize and discriminate
      structures in normal (noncancerous) and cancerous tissues by confocal Raman
      imaging, Raman spectroscopy and IR spectroscopy. The most important differences
      between normal and cancerous tissues were found in regions characteristic for
      vibrations of carotenoids, fatty acids, proteins, and interfacial water.
      Particular attention was paid to the role played by unsaturated fatty acids and
      their derivatives. K-means clustering and basis analysis followed by PCA and
      PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and
      for a statistical analysis of the samples (82 patients, 164 samples). Raman maps
      successfully identify regions of carotenoids, fatty acids, and proteins. The
      intensities, frequencies and profiles of the average Raman spectra differentiate
      the biochemical composition of normal and cancerous tissues. The paper
      demonstrates that Raman imaging has reached a clinically relevant level in regard
      to breast cancer diagnosis applications. The sensitivity and specificity obtained
      directly from PLSLD and cross validation are equal to 90.5% and 84.8% for
      calibration and 84.7% and 71.9% for cross-validation respectively. 

PMID- 25615558
TI  - Local environment of Fe dopants in nanoscale Fe : CeO(2-x) oxygen storage
      material.
AB  - Nanoscale Fe : CeO2-x oxygen storage material for the process of chemical looping
      has been investigated by advanced transmission electron microscopy and electron
      energy-loss spectroscopy before and after a model looping procedure, consisting
      of redox cycles at heightened temperature. Separately, the activity of the
      nanomaterial has been tested in a toluene total oxidation reaction. The results
      show that the material consists of ceria nanoparticles, doped with single Fe
      atoms and small FeOx clusters. The iron ion is partially present as Fe(3+) in a
      solid solution within the ceria lattice. Furthermore, enrichment of reduced
      Fe(2+) species is observed in nanovoids present in the ceria nanoparticles, as
      well as at the ceria surface. After chemical looping, agglomeration occurs and
      reduced nanoclusters appear at ceria grain boundaries formed by sintering. These
      clusters originate from surface Fe(2+) aggregation, and from bulk Fe(3+), which
      "leaks out" in reduced state after cycling to a slightly more agglomerated form.
      The activity of Fe : CeO2 during the toluene total oxidation part of the chemical
      looping cycle is ensured by the dopant Fe in the Fe1-xCexO2 solid solution, and
      by surface Fe species. These measurements on a model Fe : CeO2-x oxygen storage
      material give a unique insight into the behavior of dopants within a nanosized
      ceria host, and allow to interpret a plethora of (doped) cerium oxide-based
      reactions. 

PMID- 25615559
TI  - From mycoheterotrophy to mutualism: mycorrhizal specificity and functioning in
      Ophioglossum vulgatum sporophytes.
AB  - Mycorrhizal functioning in the fern Ophioglossum is complex and poorly
      understood. It is unknown whether mature O. vulgatum sporophytes form mutualistic
      associations with fungi of the Glomeromycota and with what specificity. Are green
      sporophytes able to 'repay' fungal carbon (C) invested in them by mycorrhizal
      partners during the initially heterotrophic gametophyte and early sporophyte
      stages of the lifecycle? We identified fungal partners of O. vulgatum sporophytes
      using molecular techniques and supplied them with (33) P-orthophosphate and O.
      vulgatum sporophytes with (14) CO2 . We traced the movement of fungal-acquired
      nutrients and plant-fixed C between symbionts and analysed natural abundance (13)
      C and (15) N isotope signatures to assess nutritional interactions. We found
      fungal specificity of O. vulgatum sporophytes towards a mycorrhizal fungus
      closely related to Glomus macrocarpum. Our radioisotope tracers revealed
      reciprocal C-for-phosphorus exchange between fern sporophytes and fungal
      partners, despite competition from surrounding vegetation. Monocultures of O.
      vulgatum were enriched in (13) C and (15) N, providing inconclusive evidence of
      mycoheterotrophy when experiencing competition from the surrounding plant
      community. We show mutualistic and specific symbiosis between a eusporangiate
      fern and fungi of the Glomeromycota. Our findings suggest a 'take now, pay later'
      strategy of mycorrhizal functioning through the lifecycle O. vulgatum, from
      mycoheterotrophic gametophyte to mutualistic aboveground sporophyte. 

PMID- 25615560
TI  - Chemisorptive enantioselectivity of chiral epoxides on tartaric-acid modified
      Pd(111): three-point bonding.
AB  - The chemisorption of two chiral molecules, propylene oxide and glycidol, is
      studied on tartaric-acid modified Pd(111) surfaces by using temperature
      programmed desorption to measure adsorbate coverage. It is found that R-glycidol
      shows preferential enantioselective chemisorption on (S,S)-tartaric acid modified
      Pd(111) surfaces, while propylene oxide does not adsorb enantioselectively. The
      enantioselectivity of glycidol depends on the tartaric acid coverage, and is
      exhibited for low tartaric acid coverages indicating that the bitartrate phase is
      responsible for the chiral recognition. The lack of enantioselectivity when using
      propylene oxide as a chiral probe implies that the enantiospecific interaction
      between glycidol and bitartate species is due to hydrogen-bonding interactions of
      the -OH group of glycidol. Scanning tunneling microscopy images were collected
      for tartaric acid adsorbed on Pd(111) under the same experimental conditions as
      used for enantioselective experiments. When tartaric acid is dosed at room
      temperature and immediately cooled to 100 K for imaging, individual bitartrate
      molecules were found. Density functional theory (DFT) calculations show that
      bitartrate binds to Pd(111) through its carboxylate groups and the -OH groups are
      oriented along the long axis of the bitartrate molecule. An enantiospecific
      interaction is found between glycidol and bitartate species where R-glycidol
      binds more strongly than S-glycidol to (S,S)-bitartate species by simultaneously
      forming hydrogen bonds with both the hydroxyl and carboxylate groups, thereby
      providing three-point bonding. 

PMID- 25615561
TI  - Diminished functional connectivity on the road to child sexual abuse in
      pedophilia.
AB  - BACKGROUND: Pedophilia is a disorder recognized for its impairment to the
      individual and for the harm it may cause to others. However, the neurobiology of
      pedophilia and a possible propensity to sexually abuse children are not well
      understood. In this study, we thus aimed at providing new insights in how
      functional integration of brain regions may relate to pedophilia or child sexual
      abuse (CSA). METHOD: By using functional magnetic resonance imaging (fMRI)
      technique, we compared functional connectivity at rest (RSFC) between pedophiles
      who engaged (P+CSA; N = 12) or did not engage (P-CSA; N = 14) in CSA and healthy
      controls (HCs; N = 14) within two networks: (i) the default mode network and (ii)
      the limbic network that has been linked to pedophilia before. RESULTS: Pedophiles
      who engaged in CSA show diminished RSFC in both networks compared with HC and P
      CSA. Most importantly, they showed diminished RSFC between the left amygdala and
      orbitofrontal as well as anterior prefrontal regions. Though significant age
      differences between groups could not be avoided, correlation control analysis did
      not provide evidence for the assumption that the RSFC effects were related to age
      differences. CONCLUSION: We found significantly diminished RSFC in brain networks
      critically involved in widespread motivational and socio-emotional processes.
      These results extend existing models of the functional neuroanatomy of pedophilia
      and CSA as altered RSFC between these regions were related to CSA rather than
      pedophilia and thus may account for an increased propensity to engage in CSA in
      people suffering from pedophilia.

PMID- 25615562
TI  - FeCl3-catalyzed self-cleaving deprotection of methoxyphenylmethyl-protected
      alcohols.
AB  - 4-Methoxyphenylmethyl ethers are widely utilized as alcohol protecting groups.
      FeCl3 effectively catalyzes the deprotection of methoxyphenylmethyl-type ethers
      in a self-cleaving manner to produce oligomeric derivatives and alcohols.
      Remarkably, the highly pure mother alcohols can be obtained without silica gel
      column chromatography by using the 2,4-dimethoxyphenylmethyl group as a
      protective group. 

PMID- 25615563
TI  - Possibility of [1,5] sigmatropic shifts in bicyclo[4.2.0]octa-2,4-dienes.
AB  - The thermal equilibration of the methyl esters of endiandric acids D and E was
      subject to a computational study. An electrocyclic pathway via an electrocyclic
      ring opening followed by a ring flip and a subsequent electrocyclization proposed
      by Nicolaou [ Nicolaou , K. C. ; Chen , J. S. Chem. Soc. Rev. 2009 , 38 , 2993 ],
      was computationally explored. The free-energy barrier for this electrocyclic
      route was shown to be very close to the bicyclo[4.2.0]octa-2,4-diene reported by
      Huisgen [ Huisgen , R. ; Boche , G. ; Dahmen , A. ; Hechtl , W. Tetrahedron Lett.
      1968 , 5215 ]. Furthermore, the possibility of a [1,5] sigmatropic alkyl group
      shift of bicyclo[4.2.0]octa-2,4-diene systems at high temperatures was explored
      in a combined computational and experimental study. Calculated reaction barriers
      for an open-shell singlet biradical-mediated stepwise [1,5] sigmatropic alkyl
      group shift were shown to be comparable with the reaction barriers for the
      bicyclo[4.1.0]hepta-2,4-diene (norcaradiene) walk rearrangement. However, the
      stepwise sigmatropic pathway is suggested to only be feasible for appropriately
      substituted compounds. Experiments conducted on a deuterated analogous diol
      derivative confirmed the calculated (large) differences in barriers between
      electrocyclic and sigmatropic pathways. 

PMID- 25615564
TI  - Genetic Sources of Subcomponents of Event-Related Potential in the Dimension of
      Psychosis Analyzed From the B-SNIP Study.
AB  - OBJECTIVE: Biological risk factors underlying psychosis are poorly understood.
      Biological underpinnings of the dimension of psychosis can be derived using
      genetic associations with intermediate phenotypes such as subcomponents of
      auditory event-related potentials (ERPs). Various ERP subcomponent abnormalities
      in schizophrenia and psychotic bipolar disorder are heritable and are expressed
      in unaffected relatives, although studies investigating genetic contributions to
      ERP abnormalities are limited. The authors used a novel parallel independent
      component analysis (para-ICA) to determine which empirically derived gene
      clusters are associated with data-driven ERP subcomponents, assuming a complex
      etiology underlying psychosis. METHOD: The authors examined the multivariate
      polygenic association of ERP subcomponents from 64-channel auditory oddball data
      in 144 individuals with schizophrenia, 210 psychotic bipolar disorder probands,
      and 95 healthy individuals from the multisite Bipolar-Schizophrenia Network on
      Intermediate Phenotypes study. Data were reduced by principal components analysis
      to two target and one standard ERP waveforms. Multivariate association of
      compressed ERP waveforms with a set of 20,329 single-nucleotide polymorphisms
      (SNPs) (reduced from a 1-million-SNP array) was examined using para-ICA. Genes
      associated with SNPs were further examined using pathway analysis tools. RESULTS:
      Para-ICA identified four ERP components that were significantly correlated with
      three genetic components. Enrichment analysis revealed complement immune response
      pathway and multiple processes that significantly mediate ERP abnormalities in
      psychosis, including synaptic cell adhesion, axon guidance, and neurogenesis.
      CONCLUSIONS: This study identified three genetic components comprising multiple
      genes mediating ERP subcomponent abnormalities in schizophrenia and psychotic
      bipolar disorder. The data suggest a possible polygenic structure comprising
      genes influencing key neurodevelopmental processes, neural circuitry, and brain
      function mediating biological pathways plausibly associated with psychosis.

PMID- 25615567
TI  - New approach based on tetrahedral-mesh geometry for accurate 4D Monte Carlo
      patient-dose calculation.
AB  - In the present study, to achieve accurate 4D Monte Carlo dose calculation in
      radiation therapy, we devised a new approach that combines (1) modeling of the
      patient body using tetrahedral-mesh geometry based on the patient's 4D CT data,
      (2) continuous movement/deformation of the tetrahedral patient model by
      interpolation of deformation vector fields acquired through deformable image
      registration, and (3) direct transportation of radiation particles during the
      movement and deformation of the tetrahedral patient model. The results of our
      feasibility study show that it is certainly possible to construct 4D patient
      models (= phantoms) with sufficient accuracy using the tetrahedral-mesh geometry
      and to directly transport radiation particles during continuous movement and
      deformation of the tetrahedral patient model. This new approach not only produces
      more accurate dose distribution in the patient but also replaces the current
      practice of using multiple 3D voxel phantoms and combining multiple dose
      distributions after Monte Carlo simulations. For routine clinical application of
      our new approach, the use of fast automatic segmentation algorithms is a must. In
      order to achieve, simultaneously, both dose accuracy and computation speed, the
      number of tetrahedrons for the lungs should be optimized. Although the current
      computation speed of our new 4D Monte Carlo simulation approach is slow (i.e. ~40
      times slower than that of the conventional dose accumulation approach), this
      problem is resolvable by developing, in Geant4, a dedicated navigation class
      optimized for particle transportation in tetrahedral-mesh geometry. 

PMID- 25615566
TI  - Treatment of maternal depression in a medication clinical trial and its effect on
      children.
AB  - OBJECTIVE: Observational studies show that when a depressed mother's symptoms
      remit, her children's psychiatric symptoms decrease. Using randomized treatment
      assignment, the authors sought to determine the differential effects of a
      depressed mother's treatment on her child. METHOD: The study was a randomized
      double-blind 12-week trial of escitalopram, bupropion, or the combination of the
      two in depressed mothers (N=76), with independent assessment of their children
      (N=135; ages 7-17 years). RESULTS: There were no significant treatment
      differences in mothers' depressive symptoms or remission. Children's depressive
      symptoms and functioning improved significantly among those whose mothers were in
      the escitalopram group (compared with those whose mothers were in the bupropion
      and combination treatment groups). Only in the escitalopram group was significant
      improvement of mother's depression associated with improvement in the child's
      symptoms. Exploratory analyses suggested that this may be due to changes in
      parental functioning: Mothers in the escitalopram group reported significantly
      greater improvement, compared with the other groups, in their ability to listen
      and talk to their children, who as a group reported that their mothers were more
      caring over the 12 weeks. Maternal baseline negative affectivity appeared to
      moderate the effect of maternal treatment on children, although the effect was
      not statistically significant. Children of mothers with low negative affectivity
      improved in all treatment groups. Children of mothers with high negative
      affectivity improved significantly only for those whose mothers were in the
      escitalopram group. CONCLUSIONS: The effects of the depressed mother's
      improvement on her children may depend on her type of treatment. Depressed
      mothers with high anxious distress and irritability may require medications that
      reduce these symptoms in order to show the effect of her remission on her
      children.

PMID- 25615565
TI  - Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy
      Comparison Subjects by Neural Activation Patterns During Response Inhibition.
AB  - OBJECTIVE: Dysfunctional response inhibition is a key executive function
      impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral
      response inhibition measures do not consistently differentiate affected from
      unaffected individuals. The authors therefore investigated neural correlates of
      response inhibition and the familial nature of these neural correlates. METHODS:
      Functional MRI measurements of neural activation during the stop-signal task and
      behavioral measures of response inhibition were obtained in adolescents and young
      adults with ADHD (N=185), their unaffected siblings (N=111), and healthy
      comparison subjects (N=124). RESULTS: Stop-signal task reaction times were longer
      and error rates were higher in participants with ADHD, but not in their
      unaffected siblings, while reaction time variability was higher in both groups
      than in comparison subjects. Relative to comparison subjects, participants with
      ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and
      frontal-parietal networks, whereby activation in inferior frontal and
      temporal/parietal nodes in unaffected siblings was intermediate between levels of
      participants with ADHD and comparison subjects. Furthermore, neural activation in
      inferior frontal nodes correlated with stop-signal reaction times, and activation
      in both inferior frontal and temporal/parietal nodes correlated with ADHD
      severity. CONCLUSIONS: Neural activation alterations in ADHD are more robust than
      behavioral response inhibition deficits and explain variance in response
      inhibition and ADHD severity. Although only affected participants with ADHD have
      deficient response inhibition, hypoactivation in inferior frontal and temporal
      parietal nodes in unaffected siblings supports the familial nature of the
      underlying neural process. Activation deficits in these nodes may be useful as
      endophenotypes that extend beyond the affected individuals in the family.

PMID- 25615568
TI  - Introducing biobased ionic liquids as the nonaqueous media for enzymatic
      synthesis of phosphatidylserine.
AB  - Biobased ionic liquids with cholinium as the cation and amino acids as the
      anions, which could be prepared from renewable biomaterials by simple
      neutralization reactions, have recently been described as promising and green
      solvents. Herein, they were successfully used as the reaction media for enzyme
      mediated transphosphatidylation of phosphatidylcholine with l-serine for
      phosphatidylserine synthesis for the first time. Our results indicated that the
      highest phosphatidylserine yield of 86.5% was achieved. Moreover, 75% original
      activity of the enzyme was maintained after being used for 10 batches. The
      present work could be considered an alternative enzymatic strategy for preparing
      phosphatidylserine. Additionally, the excellent results make the biobased ionic
      liquids more promising candidates for use as environmentally friendly solvents in
      biocatalysis fields.

PMID- 25615569
TI  - Genome-wide association study follow-up identifies cyclin A2 as a regulator of
      the transition through cytokinesis during terminal erythropoiesis.
AB  - Genome-wide association studies (GWAS) hold tremendous promise to improve our
      understanding of human biology. Recent GWAS have revealed over 75 loci associated
      with erythroid traits, including the 4q27 locus that is associated with red blood
      cell size (mean corpuscular volume). The close linkage disequilibrium block at
      this locus harbors the CCNA2 gene that encodes cyclin A2. CCNA2 mRNA is highly
      expressed in human and murine erythroid progenitor cells and regulated by the
      essential erythroid transcription factor GATA1. To understand the role of cyclin
      A2 in erythropoiesis, we have reduced expression of this gene using short hairpin
      RNAs in a primary murine erythroid culture system. We demonstrate that cyclin A2
      levels affect erythroid cell size by regulating the passage through cytokinesis
      during the final cell division of terminal erythropoiesis. Our study provides new
      insight into cell cycle regulation during terminal erythropoiesis and more
      generally illustrates the value of functional GWAS follow-up to gain mechanistic
      insight into hematopoiesis.

PMID- 25615570
TI  - High-resolution melting analysis of MED12 mutations in uterine leiomyomas in
      Chinese patients.
AB  - OBJECTIVES: Somatic mutations in mediator complex subunit 12 (MED12) have emerged
      as a critical genetic change in the development of uterine leiomyomas. Studies,
      however, have focused largely on cohorts consisting of Caucasian patients. In
      this study, uterine leiomyomas from Chinese patients were examined for MED12
      mutations. In addition, polymerase chain reaction (PCR)-based high-resolution
      melting analysis (HRMA) was compared with direct sequencing as a potentially more
      sensitive method for the detection of MED12 mutations. METHODS: Tissue samples
      with the pathologies of uterine leiomyoma (n=181) and other endometrial diseases
      (n=157) were collected from Chinese patients at the Taizhou People's Hospital and
      Taizhou Polytechnic College (Taizhou City, China). Genomic DNA was prepared from
      all samples. Both PCR-based HRMA and PCR-based direct sequencing were used to
      detect MED12 mutations. RESULTS: PCR-based HRMA and direct sequencing revealed
      MED12 mutations in 95/181 (52.5%) and 93/181 (51.4%) uterine leiomyomas,
      respectively. Nearly half of these mutations (46/93) were found in a single
      codon, codon 131. The coincidence rate between the two methods was 98.9%
      (179/181) so that no statistically significant difference was evident in the
      application of the methodologies (chi(2)=0.011, p=0.916). In addition, MED12
      mutations were identified in 1/157 (4.17%) case of other endometrial pathologies
      by both methods. CONCLUSIONS: MED12 mutations were closely associated with the
      development of uterine leiomyomas, as opposed to other uterine pathologies in
      Chinese patients, and PCR-based HRMA was found to be a reliable method for the
      detection of MED12 mutations.

PMID- 25615571
TI  - Global meaning in people with spinal cord injury: Content and changes.
AB  - BACKGROUND: After spinal cord injury (SCI), people are confronted with abrupt
      discontinuity in almost all areas of life, leading to questions on how to live a
      meaningful life again. Global meaning refers to basic ideas and goals that guide
      people in giving meaning to their lives, in specific situations. Little is known
      about global meaning relating to SCI and whether global meaning changes after
      SCI. PURPOSE: The purpose of this study was twofold: (i) to explore the content
      of global meaning of people with SCI, and (ii) to explore whether or not global
      meaning changes after SCI. METHODS: In-depth semi-structured interviews were
      conducted with 16 people with SCI. Interviews were analyzed according to the
      method of grounded theory. RESULTS: (i) Five aspects of global meaning were
      found: core values, relationships, worldview, identity and inner posture. (ii)
      Overall, little change in the content of global meaning was found after SCI;
      specific aspects of global meaning were foregrounded after SCI. CONCLUSION: Five
      aspects of global meaning were found in people with SCI. Global meaning seems
      hardly subject to change.

PMID- 25615572
TI  - Prediction of drug distribution in subcutaneous xenografts of human tumor cell
      lines and healthy tissues in mouse: application of the tissue composition-based
      model to antineoplastic drugs.
AB  - Advanced tissue composition-based models can predict the tissue-plasma partition
      coefficient (Kp ) values of drugs under in vivo conditions on the basis of in
      vitro and physiological input data. These models, however, focus on healthy
      tissues and do not incorporate data from tumors. The objective of this study was
      to apply a tissue composition-based model to six marketed antineoplastic drugs
      (docetaxel, DOC; doxorubicin, DOX; gemcitabine, GEM; methotrexate, MTX;
      topotecan, TOP; and fluorouracil, 5-FU) to predict their Kp values in three human
      tumor xenografts (HCT-116, H2122, and PC3) as well as in healthy tissues (brain,
      muscle, lung, and liver) under steady-state in vivo conditions in female NCR nude
      mice. The mechanisms considered in the tissue/tumor composition-based model are
      the binding to lipids and to plasma proteins, but the transporter effect was also
      investigated. The method consisted of analyzing tissue composition, performing
      the pharmacokinetics studies in mice, and calculating the corresponding in vivo
      Kp values. Analyses of tumor composition indicated that the tumor xenografts
      contained no or low amounts of common transporters by contrast to lipids. The
      predicted Kp values were within twofold and threefold of the measured values in
      77% and 93% of cases, respectively. However, predictions for brain for each drug,
      for liver for MTX, and for each tumor xenograft for GEM were disparate from the
      observed values, and, therefore, not well served by the model. Overall, this
      study is the first step toward the mechanism-based prediction of Kp values of
      small molecules in healthy and tumor tissues in mouse when no transporter and
      permeation limitation effect is evident. This approach will be useful in
      selecting compounds based on their abilities to penetrate human cancer xenografts
      with a physiologically based pharmacokinetic (PBPK) model, thereby increasing
      therapeutic index for chemotherapy in oncology study.

PMID- 25615573
TI  - Depression, anxiety and quality of life in long-term survivors of malignant
      melanoma: a register-based cohort study.
AB  - AIM: The purpose of the study was to determine anxiety and depression, quality of
      life, and their determinants in long-term survivors of malignant melanoma.
      METHODS: In a state cancer registry a cohort of survivors of malignant melanoma
      was contacted via the physician registered. Of 1302 contactable patients, 689
      (52.2%) completed a questionnaire including the Patient Health Questionnaire with
      generalized anxiety (GAD-7) and depression (PHQ-9) and the EORTC Quality of Life
      Questionnaire (EORTC QLQ 30). Based on multiple regression analysis, predictors
      of quality of life and distress were identified. Comparison data were assessed in
      two waves of representative face-to-face household surveys of the adult German
      population. RESULTS: An average of 8.4 (5.7 to 12.2) years after diagnosis,
      distress was higher in women compared to men and in middle adulthood (vs. older
      patients). Symptoms were higher in women than in men, and there was a decline of
      functioning and increase of symptoms across the age range of both genders.
      Compared to the general population, there were slightly increased depression and
      anxiety (only women), but no impaired global quality of life. Yet, survivors
      evidenced functional decline and more physical symptoms. Distress and reduced
      quality of life were consistently predicted by lack of social support, fear of
      recurrence, pessimism and self-blame. Distress was increased by a family history
      of melanoma, and additional mental and somatic diseases. CONCLUSION: Overall,
      long-term survivors have adjusted well achieving a global quality of life
      comparable to the general population. Yet, compromised functional dimensions,
      physical symptoms and distress indicate the need for integrating
      psychooncological screening into oncological follow-up, which might be guided by
      predictors such as family history or social support. Further prospective study is
      needed to determine the course of adaptation to the disease and corroborate the
      risk factors identified.

PMID- 25615574
TI  - Genital chlamydia prevalence in Europe and non-European high income countries:
      systematic review and meta-analysis.
AB  - BACKGROUND: Accurate information about the prevalence of Chlamydia trachomatis is
      needed to assess national prevention and control measures. METHODS: We
      systematically reviewed population-based cross-sectional studies that estimated
      chlamydia prevalence in European Union/European Economic Area (EU/EEA) Member
      States and non-European high income countries from January 1990 to August 2012.
      We examined results in forest plots, explored heterogeneity using the I2
      statistic, and conducted random effects meta-analysis if appropriate. Meta
      regression was used to examine the relationship between study characteristics and
      chlamydia prevalence estimates. RESULTS: We included 25 population-based studies
      from 11 EU/EEA countries and 14 studies from five other high income countries.
      Four EU/EEA Member States reported on nationally representative surveys of
      sexually experienced adults aged 18-26 years (response rates 52-71%). In women,
      chlamydia point prevalence estimates ranged from 3.0-5.3%; the pooled average of
      these estimates was 3.6% (95% CI 2.4, 4.8, I2 0%). In men, estimates ranged from
      2.4-7.3% (pooled average 3.5%; 95% CI 1.9, 5.2, I2 27%). Estimates in EU/EEA
      Member States were statistically consistent with those in other high income
      countries (I2 0% for women, 6% for men). There was statistical evidence of an
      association between survey response rate and estimated chlamydia prevalence;
      estimates were higher in surveys with lower response rates, (p = 0.003 in women,
      0.018 in men). CONCLUSIONS: Population-based surveys that estimate chlamydia
      prevalence are at risk of participation bias owing to low response rates.
      Estimates obtained in nationally representative samples of the general population
      of EU/EEA Member States are similar to estimates from other high income
      countries.

PMID- 25615575
TI  - A functional 12T-insertion polymorphism in the ATP1A1 promoter confers decreased
      susceptibility to hypertension in a male Sardinian population.
AB  - Identification of susceptibility genes for essential hypertension in humans has
      been a challenge due to its multifactorial pathogenesis complicated by gene-gene
      and gene-environment interactions, developmental programing and sex specific
      differences. These concurrent features make identification of causal hypertension
      susceptibility genes with a single approach difficult, thus requiring multiple
      lines of evidence involving genetic, biochemical and biological experimentation
      to establish causal functional mutations. Here we report experimental evidence
      encompassing genetic, biochemical and in vivo modeling that altogether support
      ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1
      encodes the alpha1Na,K-ATPase isoform, the sole sodium pump in vascular
      endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12
      nucleotide long thymidine (12T) insertion(ins)/deletion(del) polymorphism within
      a poly-T sequence (38T vs 26T) in the ATP1A1 5'-regulatory region associated with
      hypertension in a male Sardinian population. The 12T-insertion allele confers
      decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28-0.93])
      accounting for 12.1 mmHg decrease in systolic BP (P = 0.02) and 6.6 mmHg in
      diastolic BP (P = 0.046). The ATP1A1 promoter containing the 12T-insertion
      exhibited decreased transcriptional activity in in vitro reporter-assay systems,
      indicating decreased alpha1Na,K-ATPase expression with the 12T-insertion,
      compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased
      alpha1Na,K-ATPase expression on blood pressure, we measured blood pressure by
      radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/-
      male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/-
      mice showed significantly lower blood pressure (P < 0.03) than age-matched male
      wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected
      to lower Na-reabsorption in the kidney thereby decreasing sodium-associated risk
      for hypertension and sodium-induced endothelial stiffness and dysfunction.
      Altogether, data support ATP1A1 as a hypertension susceptibility gene in a male
      Sardinian population, and mandate further investigation of its involvement in
      hypertension in the general population. 

PMID- 25615576
TI  - Efficient generation of recombinant influenza A viruses employing a new approach
      to overcome the genetic instability of HA segments.
AB  - Influenza A viruses (IAVs) are the most relevant and continual source of severe
      infectious respiratory complications in humans and different animal species,
      especially poultry. Therefore, an efficient vaccination that elicits protective
      and neutralizing antibodies against the viral hemagglutinin (HA) and
      neuraminidase (NA) is an important strategy to counter annual epidemics or
      occasional pandemics. With the help of plasmid-based reverse genetics technology,
      it is possible that IAV vaccine strains (IVVS) are rapidly generated. However,
      the genetic instability of some cloned HA-cDNAs after transformation into
      competent bacteria represents a major obstacle. Herein, we report efficient
      cloning strategies of different genetically volatile HA segments (H5- and H9
      subtypes) employing either a newly constructed vector for reverse genetics
      (pMKPccdB) or by the use of the Escherichia coli strain HB101. Both approaches
      represent improved and generalizable strategies to establish functional reverse
      genetics systems preventing genetic changes to the cloned (HA) segments of IAV
      facilitating more efficient rescue of recombinant IAV for basic research and
      vaccine development. 

PMID- 25615578
TI  - Secondary hyperalgesia phenotypes exhibit differences in brain activation during
      noxious stimulation.
AB  - Noxious stimulation of the skin with either chemical, electrical or heat stimuli
      leads to the development of primary hyperalgesia at the site of injury, and to
      secondary hyperalgesia in normal skin surrounding the injury. Secondary
      hyperalgesia is inducible in most individuals and is attributed to central
      neuronal sensitization. Some individuals develop large areas of secondary
      hyperalgesia (high-sensitization responders), while others develop small areas
      (low-sensitization responders). The magnitude of each area is reproducible within
      individuals, and can be regarded as a phenotypic characteristic. To study
      differences in the propensity to develop central sensitization we examined
      differences in brain activity and anatomy according to individual phenotypical
      expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy
      volunteers received a first-degree burn-injury (47  degrees C, 7 min, 9 cm(2)) on
      the non-dominant lower-leg. Areas of secondary hyperalgesia were assessed 100 min
      after the injury. We measured neuronal activation by recording blood-oxygen-level
      dependent-signals (BOLD-signals) during mechanical noxious stimulation before
      burn injury and in both primary and secondary hyperalgesia areas after burn
      injury. In addition, T1-weighted images were used to measure differences in gray
      matter density in cortical and subcortical regions of the brain. We found
      significant differences in neuronal activity between high- and low-sensitization
      responders at baseline (before application of the burn-injury) (p < 0.05). After
      the burn-injury, we found significant differences between responders during
      noxious stimulation of both primary (p < 0.01) and secondary hyperalgesia (p <=
      0.04) skin areas. A decreased volume of the right (p = 0.001) and left caudate
      nucleus (p = 0.01) was detected in high-sensitization responders in comparison to
      low-sensitization responders. These findings suggest that brain-structure and
      neuronal activation to noxious stimulation differs according to secondary
      hyperalgesia phenotype. This indicates differences in central sensitization
      according to phenotype, which may have predictive value on the susceptibility to
      development of high-intensity acute and persistent pain.

PMID- 25615577
TI  - Effects of crowding and attention on high-levels of motion processing and motion
      adaptation.
AB  - The motion after-effect (MAE) persists in crowding conditions, i.e., when the
      adaptation direction cannot be reliably perceived. The MAE originating from
      complex moving patterns spreads into non-adapted sectors of a multi-sector
      adapting display (i.e., phantom MAE). In the present study we used global
      rotating patterns to measure the strength of the conventional and phantom MAEs in
      crowded and non-crowded conditions, and when attention was directed to the
      adapting stimulus and when it was diverted away from the adapting stimulus. The
      results show that: (i) the phantom MAE is weaker than the conventional MAE, for
      both non-crowded and crowded conditions, and when attention was focused on the
      adapting stimulus and when it was diverted from it, (ii) conventional and phantom
      MAEs in the crowded condition are weaker than in the non-crowded condition.
      Analysis conducted to assess the effect of crowding on high-level of motion
      adaptation suggests that crowding is likely to affect the awareness of the
      adapting stimulus rather than degrading its sensory representation, (iii) for
      high-level of motion processing the attentional manipulation does not affect the
      strength of either conventional or phantom MAEs, neither in the non-crowded nor
      in the crowded conditions. These results suggest that high-level MAEs do not
      depend on attention and that at high-level of motion adaptation the effects of
      crowding are not modulated by attention. 

PMID- 25615580
TI  - The Challenge: Carbon nanomaterials in the environment: New threats or wonder
      materials?

PMID- 25615579
TI  - Development of delayed bitterness and effect of harvest date in stored juice from
      two complex citrus hybrids.
AB  - BACKGROUND: Mandarins and mandarin hybrids have excellent flavor and color
      attributes, making them good candidates for consumption as fresh fruit. When
      processed into juice, however, they are less palatable, as they develop delayed
      bitterness when stored for a period of time. In this study the kinetics of
      delayed bitterness in two citrus mandarin hybrid siblings, 'Ambersweet' and USDA
      1-105-106, was explored by sensory and instrumental analyses. In addition to the
      bitter limonoids, other quality factors (i.e. sugars, acids, pH, soluble solids
      content (SSC), titratable acidity (TA) and the ratio SSC/TA) were also measured.
      RESULTS: The two citrus hybrid siblings had different chemical profiles, which
      were perceived by taste panels. USDA 1-105-106 developed delayed bitterness when
      the juice was stored for more than 4 h, similar to juice from 'Navel' oranges,
      but 'Ambersweet' did not. Bitterness in 'Ambersweet' was more affected by harvest
      maturity, as juice from earlier harvest had lower SSC but higher TA and bitter
      limonoids. CONCLUSION: Since juice of USDA 1-105-106 shows delayed bitterness
      when stored for more than 4 h, this cultivar is not suitable for juice
      processing. Our finding that siblings can differ in chemical and sensory
      properties emphasize the importance of post-processing storage studies before
      releasing cultivars for juice.

PMID- 25615581
TI  - Male poplars have a stronger ability to balance growth and carbohydrate
      accumulation than do females in response to a short-term potassium deficiency.
AB  - Potassium (K) deficiency influences plant performance, such as ion uptake and
      carbohydrate transport. However, little is known about differences between males
      and females in response to K deficiency. In this study, dry matter accumulation,
      photosynthetic capacity, allocation patterns of K(+) , Na(+) and carbohydrates,
      and ultrastructural changes in males and females of Populus cathayana exposed to
      K deficiency were investigated. The results indicated that males maintained a
      significantly higher K(+) content and K(+) /Na(+) ratio in leaves and stems than
      did females under K deficiency. Moreover, K deficiency significantly increased
      the sucrose content of females, whereas no significant effect on males was
      detected. In addition, a comparative analysis showed that males allocated more
      resources to roots, while females allocated more to leaves, which resulted in
      sexually different root/shoot (R/S) ratios. Transmission electron microscopic
      (TEM) observations showed that males suffered fewer injuries than did females.
      These results suggested that males have a better ability to cope with K
      deficiency. In addition, the combined effects of salinity and K deficiency on
      poplars were studied. The results indicated that salt stress aggravates the
      negative effects caused by K deficiency. Taken together, our study provided
      evidence for gender-specific strategies in ion and carbohydrate allocation in
      poplars exposed to a short-term K deficiency. In leaves and stems, the lower K(+)
      accumulation inhibited sucrose translocation and resulted in a decreased R/S
      ratio, which may contribute to males having a stronger ability to balance growth
      and carbohydrate accumulation when compared with females. 

PMID- 25615583
TI  - A path to eradication of hepatitis C in low- and middle-income countries.
AB  - We are entering a new era in the treatment of hepatitis C virus (HCV) infection
      and almost all patient groups in high-income countries have the potential to be
      cured with all-oral, highly potent combinations of direct-acting antiviral drugs.
      Soon the main barrier to curing hepatitis C, even in wealthy countries, will be
      the high price of these all-oral regimens. The gulf between the advances in HCV
      drug development and access to treatment for individual patients will be even
      greater in low- and middle-income countries (LMIC) where 80% of the global burden
      of HCV infection and mortality exists. Ensuring that people in LMIC have access
      to regimens against HCV will require a similar level of advocacy and public
      private partnerships as has transformed the control of other global diseases such
      as HIV. Numerous challenges will need to be overcome. These include improving low
      cost diagnostic tests, especially in sub-Saharan Africa where the false-positive
      rate is unacceptably high, reducing iatrogenic spread of HCV, addressing
      transmission among people who inject drugs (PWID), and ensuring affordable access
      to antiviral treatment for all people living with HCV infection in LMIC. This
      article forms part of a symposium in Antiviral Research on "Hepatitis C: next
      steps toward global eradication." 

PMID- 25615582
TI  - Role of neurochemical navigation with 5-aminolevulinic acid during intraoperative
      MRI-guided resection of intracranial malignant gliomas.
AB  - OBJECTIVE: To evaluate the role of the neurochemical navigation with 5
      aminolevulinic acid (5-ALA) during intraoperative MRI (iMRI)-guided resection of
      the intracranial malignant gliomas. METHODS: The analysis included 99 consecutive
      surgical cases. Resection of the bulk of the neoplasm was mainly guided by the
      updated neuronavigation based on the low-field-strength (0.3T) iMRI, whereas at
      the periphery of the lesion neurochemical navigation with 5-ALA was additionally
      used. RESULTS: In total, 286 tissue specimens were obtained during surgeries for
      histopathological examination. According to iMRI 98 samples with strong (91
      cases), weak (6 cases), or absent (1 case) fluorescence corresponded to the bulk
      of the lesion and all of those ones contained tumor. Out of 188 tissue specimens
      obtained from the "peritumoral brain," the neoplastic elements were identified in
      89%, 81% and 29% of samples with, respectively, strong (107 cases), weak (47
      cases) and absent (34 cases) fluorescence. Positive predictive values of the
      tissue fluorescence for presence of neoplasm within and outside of its boundaries
      on iMRI were 100% and 86%, respectively. CONCLUSION: Neurochemical navigation
      with 5-ALA is useful adjunct during iMRI-guided resection of intracranial
      malignant gliomas, which allows identification of the tumor extension beyond its
      radiological borders.

PMID- 25615584
TI  - Biogenesis of thylakoid membranes.
AB  - Thylakoids mediate photosynthetic electron transfer and represent one of the most
      elaborate energy-transducing membrane systems. Despite our detailed knowledge of
      its structure and function, much remains to be learned about how the machinery is
      put together. The concerted synthesis and assembly of lipids, proteins and low
      molecular-weight cofactors like pigments and transition metal ions require a high
      level of spatiotemporal coordination. While increasing numbers of assembly
      factors are being functionally characterized, the principles that govern how
      thylakoid membrane maturation is organized in space are just starting to emerge.
      In both cyanobacteria and chloroplasts, distinct production lines for the
      fabrication of photosynthetic complexes, in particular photosystem II, have been
      identified. This article is part of a Special Issue entitled: Chloroplast
      Biogenesis. 

PMID- 25615585
TI  - Identification of common motifs in the regulation of light harvesting: The case
      of cyanobacteria IsiA.
AB  - When cyanobacteria are grown under iron-limited or other oxidative stress
      conditions the iron stress inducible pigment-protein IsiA is synthesized in
      variable amounts. IsiA accumulates in aggregates inside the photosynthetic
      membrane that strongly dissipate chlorophyll excited state energy. In this paper
      we applied Stark fluorescence (SF) spectroscopy at 77K to IsiA aggregates to gain
      insight into the nature of the emitting and energy dissipating state(s). Our
      study shows that two emitting states are present in the system, one emitting at
      684 nm and the other emitting at about 730 nm. The new 730 nm state exhibits
      strongly reduced fluorescence (F) together with a large charge transfer
      character. We discuss these findings in the light of the energy dissipation
      mechanisms involved in the regulation of photosynthesis in plants, cyanobacteria
      and diatoms. Our results suggest that photosynthetic organisms have adopted
      common mechanisms to cope with the deleterious effects of excess light under
      unfavorable growth conditions.

PMID- 25615586
TI  - Photoinduction of cyclosis-mediated interactions between distant chloroplasts.
AB  - Communications between chloroplasts and other organelles based on the exchange of
      metabolites, including redox active substances, are recognized as a part of
      intracellular regulation, chlororespiration, and defense against oxidative
      stress. Similar communications may operate between spatially distant chloroplasts
      in large cells where photosynthetic and respiratory activities are distributed
      unevenly under fluctuating patterned illumination. Microfluorometry of
      chlorophyll fluorescence in vivo in internodal cells of the alga Chara corallina
      revealed that a 30-s pulse of localized light induces a transient increase (~25%)
      in F' fluorescence of remote cell parts exposed to dim background light at a 1.5
      mm distance on the downstream side from the illuminated spot in the plane of
      unilateral cytoplasmic streaming but has no effect on F' at equal distance on the
      upstream side. An abrupt arrest of cytoplasmic streaming for about 30s by
      triggering the action potential extended either the ascending or descending
      fronts of the F' fluorescence response, depending on the exact moment of
      streaming cessation. The response of F' fluorescence to localized illumination of
      a distant cell region was absent in dark-adapted internodes, when the localized
      light was applied within the first minute after switching on continuous
      background illumination of the whole cell, but it appeared in full after longer
      exposures to continuous background light. These results and the elimination of
      the F' response by methyl viologen known to redirect electron transport pathways
      beyond photosystem I indicate the importance of photosynthetic induction and the
      stromal redox state for long-distance communications of chloroplasts in vivo. 

PMID- 25615587
TI  - Photosystem II repair in plant chloroplasts--Regulation, assisting proteins and
      shared components with photosystem II biogenesis.
AB  - Photosystem (PS) II is a multisubunit thylakoid membrane pigment-protein complex
      responsible for light-driven oxidation of water and reduction of plastoquinone.
      Currently more than 40 proteins are known to associate with PSII, either stably
      or transiently. The inherent feature of the PSII complex is its vulnerability in
      light, with the damage mainly targeted to one of its core proteins, the D1
      protein. The repair of the damaged D1 protein, i.e. the repair cycle of PSII,
      initiates in the grana stacks where the damage generally takes place, but
      subsequently continues in non-appressed thylakoid domains, where many steps are
      common for both the repair and de novo assembly of PSII. The sequence of the
      (re)assembly steps of genuine PSII subunits is relatively well-characterized in
      higher plants. A number of novel findings have shed light into the regulation
      mechanisms of lateral migration of PSII subcomplexes and the repair as well as
      the (re)assembly of the complex. Besides the utmost importance of the PSII repair
      cycle for the maintenance of PSII functionality, recent research has pointed out
      that the maintenance of PSI is closely dependent on regulation of the PSII repair
      cycle. This review focuses on the current knowledge of regulation of the repair
      cycle of PSII in higher plant chloroplasts. Particular emphasis is paid on
      sequential assembly steps of PSII and the function of the number of PSII
      auxiliary proteins involved both in the biogenesis and repair of PSII. This
      article is part of a Special Issue entitled: Chloroplast Biogenesis. 

PMID- 25615588
TI  - Incidence of viral infection detected by PCR and real-time PCR in childhood
      community-acquired pneumonia: a meta-analysis.
AB  - Several studies examining the incidence of viral infection in childhood community
      acquired pneumonia (CAP) utilizing polymerase chain reaction (PCR) or real-time
      PCR methods have been reported. We systematically searched Pubmed and Embase for
      studies reporting the incidence of respiratory viral infection in childhood CAP.
      The pooled incidences of viral infection were calculated with a random-effects
      model. Sources of heterogeneity were explored by subgroup analysis and a
      univariant metaregression analysis. We included 21 eligible reports in our study.
      We found significant heterogeneity on the incidence of viral infection in
      childhood CAP. The random effects pooled incidence was 57.4% (95% confidence
      interval (CI): 50.8-64.1). The pooled incidence of mixed infection was 29.3%
      (95%CI: 23.0-35.6) with considerable heterogeneity. The pooled incidence of mixed
      infection was 29.3% (95%CI: 23.0-35.6). Rhinovirus, respiratory syncytial virus
      (RSV) and bocavirus were found to be the three most common viruses in childhood
      CAP. We also demonstrated that respiratory viruses were detected in 76.1% of
      patients aged <= 1 year, 63.1% of patients aged 2-5 years and 27.9% of patients
      aged >= 6 years. We conclude that respiratory viruses are widely detected in
      paediatric patients with CAP by PCR or real-time PCR methods. More than half of
      viral infections are probably concurrent with bacterial infections. Rhinovirus,
      RSV and bocavirus are the three most frequent viruses identified in childhood
      CAP; the incidence of viral infection decreased with age.

PMID- 25615589
TI  - Trafficking of Acetyl-C16-Ceramide-NBD with Long-Term Stability and No
      Cytotoxicity into the Golgi Complex.
AB  - The Golgi complex plays a prominent role in the modification and sorting of
      lipids and proteins, and is a highly dynamic organelle that is dispersed and
      rearranged before and after mitosis. Several reagents including 4-nitrobenzo-2
      oxa-1,3-diazole-labeled C6-ceramide (NBD-C6-ceramide, a ceramide having an NBD
      bound C6-N-acyl chain) and Golgi-specific proteins that emit fluorescence are
      used as Golgi markers. In the present study, we synthesized a new ceramide
      analog, acetyl-C16-ceramide-NBD (a ceramide having an acetylated C-1 hydroxyl
      group, C16-N-acyl chain, and NBD-bound C15-sphingosine), and showed that it
      preferentially accumulated in the Golgi complex without cytotoxicity for over 24
      h. Pathways for cellular uptake and interorganelle trafficking of acetyl-C16
      ceramide-NBD were investigated. Acetyl-C16-ceramide-NBD was transported to the
      Golgi complex via ceramide transport proteins. In contrast to NBD-C6-ceramide,
      acetyl-C16-ceramide-NBD was resistant to ceramide metabolic enzymes such as
      sphingomyelin synthase and glucosylceramide synthase. Because of its weaker
      cytotoxicity and resistance to ceramide metabolic enzymes, the localization of
      the Golgi complex could be observed in acetyl-C16-ceramide-NBD-labeled cells
      before and after mitosis. 

PMID- 25615590
TI  - Deficiency of Factor VII activating protease alters the outcome of ischemic
      stroke in mice.
AB  - Factor VII activating protease (FSAP) is a circulating protease with a putative
      role in hemostasis, remodeling and inflammation. A polymorphism giving rise to
      low proteolytic activity has been associated with an increased risk of stroke and
      carotid stenosis. To date, no in vivo studies or mechanistic information is
      available to explain these results. Based on the polymorphism data we hypothesize
      that a lack of endogenous FSAP will increase the severity of stroke. Stroke was
      induced by applying thrombin in the middle cerebral artery in wild-type (WT) and
      FSAP(-/-) mice. Increased stroke volume and worsened neurological deficit were
      observed in FSAP(-/-) mice. Raised levels of FSAP protein were detected in the
      infarcted area of WT mice together with enhanced leukocyte infiltration and
      apoptosis in FSAP(-/-) mice. There was a concomitant increase in the activation
      of the NFkappaB pathway and decrease in expression of the PI3K/AKT pathway
      proteins. At a cellular level, FSAP increased cell survival and decreased
      apoptosis in primary cortical neurons and astrocytes exposed to tPA/NMDA
      excitotoxicity or oxygen glucose deprivation (OGD)/reoxygenation, respectively.
      This was mediated via the PI3K/AKT pathway with involvement of the protease
      activated receptor-1. To corroborate the human epidemiological data, which link
      FSAP with stroke, we now show that the lack of FSAP in mice worsens the outcome
      of stroke. In the absence of FSAP there was a stronger inflammatory response and
      lower cell survival due to insufficient activation of the PI3K/AKT pathway. 

PMID- 25615591
TI  - Comparative Population Genomics Reveals Strong Divergence and Infrequent
      Introgression between Asian and African Rice.

PMID- 25615593
TI  - Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1/2 dependent way
      in human colorectal cancer cells.
AB  - Tanshinone I (TAN I) as one of the naturally occurring diterpenes from Salvia
      miltiorrhizae Bunge (Danshen) has been reported to exhibit an anti-cancer
      activity. However, the underlying mechanisms are still poorly understood. Thus,
      we performed in vitro study to elucidate the biological mechanism by which TAN I
      may induce the inhibition of cell growth in human colorectal cancer cells. The
      treatment of TAN I suppressed the cell proliferation in HCT116 and SW480 cells
      and decreased the level of cyclin D1 protein. However, the mRNA level of cyclin
      D1 did not changed by TAN I treatment. Inhibition of proteasomal degradation by
      MG132 blocked TAN I-mediated cyclin D1 downregulation and the half-life of cyclin
      D1 was decreased in the cells treated with TAN I. In addition, phosphorylation of
      cyclin D1 at threonine-286 was increased by TAN I and a point mutation of
      threonine-286 to alanine attenuated TAN I-mediated cyclin D1 downregulation.
      Inhibition of ERK1/2 suppressed cyclin D1 phosphorylation and subsequent
      downregulation by TAN I. From these results, we suggest that TAN I-mediated
      cyclin D1 downregulation may result from proteasomal degradation through its
      ERK1/2-mediated phosphorylation of threonine-286. In conclusion, the current
      study provides new mechanistic link between TAN I, cyclin D1 downregulation and
      cell growth in human colorectal cancer cells. 

PMID- 25615592
TI  - Laminar and dorsoventral molecular organization of the medial entorhinal cortex
      revealed by large-scale anatomical analysis of gene expression.
AB  - Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position
      and orientation in space. Within the MEC spatial representations, including grid
      and directional firing fields, have a laminar and dorsoventral organization that
      corresponds to a similar topography of neuronal connectivity and cellular
      properties. Yet, in part due to the challenges of integrating anatomical data at
      the resolution of cortical layers and borders, we know little about the molecular
      components underlying this organization. To address this we develop a new
      computational pipeline for high-throughput analysis and comparison of in situ
      hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH
      data for over 16,000 genes in the Allen Brain Atlas and validate our analysis
      with RNA sequencing of MEC tissue from adult mice. We find that differential gene
      expression delineates the borders of the MEC with neighboring brain structures
      and reveals its laminar and dorsoventral organization. We propose a new molecular
      basis for distinguishing the deep layers of the MEC and show that their
      similarity to corresponding layers of neocortex is greater than that of
      superficial layers. Our analysis identifies ion channel-, cell adhesion- and
      synapse-related genes as candidates for functional differentiation of MEC layers
      and for encoding of spatial information at different scales along the
      dorsoventral axis of the MEC. We also reveal laminar organization of genes
      related to disease pathology and suggest that a high metabolic demand predisposes
      layer II to neurodegenerative pathology. In principle, our computational pipeline
      can be applied to high-throughput analysis of many forms of neuroanatomical data.
      Our results support the hypothesis that differences in gene expression contribute
      to functional specialization of superficial layers of the MEC and dorsoventral
      organization of the scale of spatial representations. 

PMID- 25615594
TI  - Sleep and the endogenous melatonin rhythm of high arctic residents during the
      summer and winter.
AB  - The seasonal extremes of photoperiod in high latitudes place particular strain on
      the human circadian system. Arctic residence has been associated with poor sleep
      in both summer and winter. The goal of the work reported here was to study the
      circadian rhythms of individuals living in the high Arctic by measuring sleep
      variables and the timing of melatonin production. Two research trials were
      conducted in the built environment of CFS Alert (82 degrees  29' 58" N).
      Participants wore motion logging devices (actigraphs), which measure ambient
      light as well as motion, for 1week to provide data on sleep quantity, quality and
      light exposure. On the penultimate day of each trial, the participants were
      maintained together in a gymnasium with lounge chairs and saliva was collected at
      regular intervals to measure melatonin and assess the dim light melatonin onset
      (DLMO), offset (MelOFF), 50% rise and fall times of the whole profile and total
      production. In general, sleep duration was found to be significantly different
      between the January and June data collections at CFS Alert, with participants in
      June sleeping 50min on average less each day compared to their January
      counterparts. In June sleep was mistimed in many subjects relative to circadian
      phase as evidenced by the melatonin rhythm. Exposure to bright evening light was
      the most likely causal factor and should be avoided in the Arctic summer. The
      Arctic summer represents a particularly challenging environment for obtaining
      sufficient sleep. This has implications for the cognitive performance of staff
      during work hours. 

PMID- 25615595
TI  - Decision-making for risky gains and losses among college students with Internet
      gaming disorder.
AB  - Individuals with Internet gaming disorder (IGD) tend to exhibit disadvantageous
      risky decision-making not only in their real life but also in laboratory tasks.
      Decision-making is a complex multifaceted function and different cognitive
      processes are involved in decision-making for gains and losses. However, the
      relationship between impaired decision-making and gain versus loss processing in
      the context of IGD is poorly understood. The main aim of the present study was to
      separately evaluate decision-making for risky gains and losses among college
      students with IGD using the Cups task. Additionally, we further examined the
      effects of outcome magnitude and probability level on decision-making related to
      risky gains and losses respectively. Sixty college students with IGD and 42
      matched healthy controls (HCs) participated. Results indicated that IGD subjects
      exhibited generally greater risk taking tendencies than HCs. In comparison to
      HCs, IGD subjects made more disadvantageous risky choices in the loss domain (but
      not in the gain domain). Follow-up analyses indicated that the impairment was
      associated to insensitivity to changes in outcome magnitude and probability level
      for risky losses among IGD subjects. In addition, higher Internet addiction
      severity scores were associated with percentage of disadvantageous risky options
      in the loss domain. These findings emphasize the effect of insensitivity to
      losses on disadvantageous decisions under risk in the context of IGD, which has
      implications for future intervention studies. 

PMID- 25615596
TI  - Avoiding toxic levels of essential minerals: a forgotten factor in deer diet
      preferences.
AB  - Ungulates select diets with high energy, protein, and sodium contents. However,
      it is scarcely known the influence of essential minerals other than Na in diet
      preferences. Moreover, almost no information is available about the possible
      influence of toxic levels of essential minerals on avoidance of certain plant
      species. The aim of this research was to test the relative importance of mineral
      content of plants in diet selection by red deer (Cervus elaphus) in an annual
      basis. We determined mineral, protein and ash content in 35 common Mediterranean
      plant species (the most common ones in the study area). These plant species were
      previously classified as preferred and non-preferred. We found that deer
      preferred plants with low contents of Ca, Mg, K, P, S, Cu, Sr and Zn. The model
      obtained was greatly accurate identifying the preferred plant species (91.3% of
      correct assignments). After a detailed analysis of these minerals (considering
      deficiencies and toxicity levels both in preferred and non-preferred plants) we
      suggest that the avoidance of excessive sulphur in diet (i.e., selection for
      plants with low sulphur content) seems to override the maximization for other
      nutrients. Low sulphur content seems to be a forgotten factor with certain
      relevance for explaining diet selection in deer. Recent studies in livestock
      support this conclusion, which is highlighted here for the first time in diet
      selection by a wild large herbivore. Our results suggest that future studies
      should also take into account the toxicity levels of minerals as potential
      drivers of preferences. 

PMID- 25615597
TI  - Antiresorptive agents increase the effects of exercise on preventing
      postmenopausal bone loss in women: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: It remains unknown whether the combination of
      antiresorptive agents and exercise would generate additive effects on bone
      mineral density (BMD) in postmenopausal women, though their separate roles in
      preventing bone loss have been well established. This meta-analysis aimed to
      evaluate the combined impact of antiresorptive treatment and exercise on the
      lumbar spine and femoral neck BMD in postmenopausal women compared with an
      exercise-only intervention. METHODS: A systematic literature search of PubMed,
      EMBASE, SportDiscus and ProQuest up to Jun 2014 was conducted to identify the
      influence of antiresorptive agents and exercise on BMD in postmenopausal women.
      The study quality of the included trials was evaluated. The effect sizes were
      estimated by calculating the standardized mean difference (SMD). Subgroup
      analyses were conducted by pharmacological regimens and exercise categories.
      RESULTS: Nine studies with a total of 1,248 postmenopausal women met the
      inclusion criteria. The heterogeneity between the studies was evident at the
      spine (I2 = 78.7%) and hip (I2 = 41.7%) measurements; random-effects models were
      used in the data analysis. The pooled effect sizes associated with the combined
      interventions of antiresorptive agents and exercise were significant at the
      lumbar spine BMD (SMD = 0.511, 95% CI = 0.118-0.904, p = 0.011). Combining
      hormone replacement therapy (HRT) and exercise training generated greater
      beneficial effects on lumbar spine (SMD = 0.729, 95% CI = 0.186-1.273, p = 0.009)
      and femoral neck BMD (SMD = 0.220, 95% CI = 0.0110-429, p = 0.039) than the
      exercise-only intervention. Impact exercise was sensitive to antiresorptive
      agents in preventing postmenopausal bone loss both at the spine (SMD = 1.252,
      95%CI = 0.465-2.039, p = 0.002) and hips (SMD = 0.414, 95%CI = 0.106-0.723, p =
      0.008). CONCLUSIONS: Our findings indicate that antiresorptive agents
      significantly increase the impact of exercise on the prevention of bone loss in
      postmenopausal women, which implies that the combination of antiresorptive agents
      and exercise may generate additive effects.

PMID- 25615598
TI  - Hydrogen sulfide donor protects porcine oocytes against aging and improves the
      developmental potential of aged porcine oocytes.
AB  - Porcine oocytes that have matured in in vitro conditions undergo the process of
      aging during prolonged cultivation, which is manifested by spontaneous
      parthenogenetic activation, lysis or fragmentation of aged oocytes. This study
      focused on the role of hydrogen sulfide (H2S) in the process of porcine oocyte
      aging. H2S is a gaseous signaling molecule and is produced endogenously by the
      enzymes cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE) and 3
      mercaptopyruvate sulfurtransferase (MPST). We demonstrated that H2S-producing
      enzymes are active in porcine oocytes and that a statistically significant
      decline in endogenous H2S production occurs during the first day of aging.
      Inhibition of these enzymes accelerates signs of aging in oocytes and
      significantly increases the ratio of fragmented oocytes. The presence of
      exogenous H2S from a donor (Na2S.9H2O) significantly suppressed the
      manifestations of aging, reversed the effects of inhibitors and resulted in the
      complete suppression of oocyte fragmentation. Cultivation of aging oocytes in the
      presence of H2S donor positively affected their subsequent embryonic development
      following parthenogenetic activation. Although no unambiguous effects of
      exogenous H2S on MPF and MAPK activities were detected and the intracellular
      mechanism underlying H2S activity remains unclear, our study clearly demonstrates
      the role of H2S in the regulation of porcine oocyte aging. 

PMID- 25615599
TI  - Understanding the black box: a systematic review of the measurement of the
      community mobilization process in evaluations of interventions targeting sexual,
      reproductive, and maternal health.
AB  - Community mobilization (CM) interventions are often used to improve sexual,
      reproductive, and maternal health (SRMH). This systematic review provides an
      overview of CM indicators used in evaluation and then focuses on the use of
      linking constructs-those measures of the process of CM between programmatic
      outputs and outcomes. We identified 108 English-language articles evaluating 86
      CM interventions that target SRMH. Content analysis was used to code CM
      indicators into five categories: qualitative descriptions of CM; participation,
      diffusion and community action indicators that measure tangible, programmatic
      outputs; and linking constructs that capture the process of moving from
      participation to empowerment. Fifty-five (64.0%) interventions include a CM
      indicator. Diffusion indicators are most common (56.4%); linking constructs are
      least common (20.0%). We found 23 linking constructs used in evaluations of 11
      interventions, with limited information on psychometric properties available.
      Three evaluations report positive relationships between linking constructs and
      condom use, one of which was significant in multivariate analysis. To better
      understand how CM leads to improved outcomes, we recommend increasing the
      measurement of linking constructs in evaluations of CM interventions. Research
      should focus on developing and validating new linking construct indicators and
      better disseminating existing measurement tools. 

PMID- 25615600
TI  - Re-examination of Chinese semantic processing and syntactic processing: evidence
      from conventional ERPs and reconstructed ERPs by residue iteration decomposition
      (RIDE).
AB  - A number of studies have explored the time course of Chinese semantic and
      syntactic processing. However, whether syntactic processing occurs earlier than
      semantics during Chinese sentence reading is still under debate. To further
      explore this issue, an event-related potentials (ERPs) experiment was conducted
      on 21 native Chinese speakers who read individually-presented Chinese simple
      sentences (NP1+VP+NP2) word-by-word for comprehension and made semantic
      plausibility judgments. The transitivity of the verbs was manipulated to form
      three types of stimuli: congruent sentences (CON), sentences with a semantically
      violated NP2 following a transitive verb (semantic violation, SEM), and sentences
      with a semantically violated NP2 following an intransitive verb (combined
      semantic and syntactic violation, SEM+SYN). The ERPs evoked from the target NP2
      were analyzed by using the Residue Iteration Decomposition (RIDE) method to
      reconstruct the ERP waveform blurred by trial-to-trial variability, as well as by
      using the conventional ERP method based on stimulus-locked averaging. The
      conventional ERP analysis showed that, compared with the critical words in CON,
      those in SEM and SEM+SYN elicited an N400-P600 biphasic pattern. The N400 effects
      in both violation conditions were of similar size and distribution, but the P600
      in SEM+SYN was bigger than that in SEM. Compared with the conventional ERP
      analysis, RIDE analysis revealed a larger N400 effect and an earlier P600 effect
      (in the time window of 500-800 ms instead of 570-810ms). Overall, the combination
      of conventional ERP analysis and the RIDE method for compensating for trial-to
      trial variability confirmed the non-significant difference between SEM and
      SEM+SYN in the earlier N400 time window. Converging with previous findings on
      other Chinese structures, the current study provides further precise evidence
      that syntactic processing in Chinese does not occur earlier than semantic
      processing. 

PMID- 25615602
TI  - Effect of natural and semisynthetic pseudoguianolides on the stability of NF
      kappaB:DNA complex studied by agarose gel electrophoresis.
AB  - The nuclear factor kappaB (NF-kappaB) is a promising target for drug discovery.
      NF-kappaB is a heterodimeric complex of RelA and p50 subunits that interact with
      the DNA, regulating the expression of several genes; its dysregulation can
      trigger diverse diseases including inflammation, immunodeficiency, and cancer.
      There is some experimental evidence, based on whole cells studies, that natural
      sesquiterpene lactones (Sls) can inhibit the interaction of NF-kappaB with DNA,
      by alkylating the RelA subunit via a Michael addition. In the present work, 28
      natural and semisynthetic pseudoguianolides were screened as potential inhibitors
      of NF-kappaB in a biochemical assay that was designed using pure NF-kappaB
      heterodimer, pseudoguianolides and a ~1000 bp palindromic DNA fragment harboring
      two NF-kappaB recognition sequences. By comparing the relative amount of free DNA
      fragment to the NF-kappaB - DNA complex, in a routine agarose gel
      electrophoresis, the destabilizing effect of a compound on the complex is
      estimated. The results of the assay and the following structure-activity
      relationship study, allowed the identification of several relevant structural
      features in the pseudoguaianolide skeleton, which are necessary to enhance the
      dissociating capacity of NF-kappaB-DNA complex. The most active compounds are
      substituted at C-3 (alpha-carbonyl), in addition to having the alpha-methylene
      gamma-lactone moiety which is essential for the alkylation of RelA. 

PMID- 25615601
TI  - The intersection of the extrinsic hedgehog and WNT/wingless signals with the
      intrinsic Hox code underpins branching pattern and tube shape diversity in the
      drosophila airways.
AB  - The tubular networks of the Drosophila respiratory system and our vasculature
      show distinct branching patterns and tube shapes in different body regions. These
      local variations are crucial for organ function and organismal fitness.
      Organotypic patterns and tube geometries in branched networks are typically
      controlled by variations of extrinsic signaling but the impact of intrinsic
      factors on branch patterns and shapes is not well explored. Here, we show that
      the intersection of extrinsic hedgehog(hh) and WNT/wingless (wg) signaling with
      the tube-intrinsic Hox code of distinct segments specifies the tube pattern and
      shape of the Drosophila airways. In the cephalic part of the airways, hh
      signaling induces expression of the transcription factor (TF) knirps (kni) in the
      anterior dorsal trunk (DTa1). kni represses the expression of another TF spalt
      major (salm), making DTa1 a narrow and long tube. In DTa branches of more
      posterior metameres, Bithorax Complex (BX-C) Hox genes autonomously divert hh
      signaling from inducing kni, thereby allowing DTa branches to develop as salm
      dependent thick and short tubes. Moreover, the differential expression of BX-C
      genes is partly responsible for the anterior-to-posterior gradual increase of the
      DT tube diameter through regulating the expression level of Salm, a
      transcriptional target of WNT/wg signaling. Thus, our results highlight how tube
      intrinsic differential competence can diversify tube morphology without changing
      availabilities of extrinsic factors. 

PMID- 25615603
TI  - Free access to a running-wheel advances the phase of behavioral and physiological
      circadian rhythms and peripheral molecular clocks in mice.
AB  - Behavioral and physiological circadian rhythms are controlled by endogenous
      oscillators in animals. Voluntary wheel-running in rodents is thought to be an
      appropriate model of aerobic exercise in humans. We evaluated the effects of
      chronic voluntary exercise on the circadian system by analyzing temporal profiles
      of feeding, core body temperature, plasma hormone concentrations and peripheral
      expression of clock and clock-controlled genes in mice housed under sedentary
      (SED) conditions or given free access to a running-wheel (RW) for four weeks.
      Voluntary wheel-running activity advanced the circadian phases of increases in
      body temperature, food intake and corticosterone secretion in the mice. The
      circadian expression of clock and clock-controlled genes was tissue- and gene
      specifically affected in the RW mice. The temporal expression of E-box-dependent
      circadian clock genes such as Per1, Per2, Nr1d1 and Dbp were slightly, but
      significantly phase-advanced in the liver and white adipose tissue, but not in
      brown adipose tissue and skeletal muscle. Peak levels of Per1, Per2 and Nr1d1
      expression were significantly increased in the skeletal muscle of RW mice. The
      circadian phase and levels of hepatic mRNA expression of the clock-controlled
      genes that are involved in cholesterol and fatty acid metabolism significantly
      differed between SED and RW mice. These findings indicated that endogenous clock
      governed voluntary wheel-running activity provides feedback to the central
      circadian clock that systemically governs behavioral and physiological rhythms. 

PMID- 25615604
TI  - Biochemical requirements for two Dicer-like activities from wheat germ.
AB  - RNA silencing pathways were first discovered in plants. Through genetic analysis,
      it has been established that the key silencing components called Dicer-like (DCL)
      genes have been shown to cooperatively process RNA substrates of multiple origin
      into distinct 21, 22 and 24 nt small RNAs. However, only few detailed biochemical
      analysis of the corresponding complexes has been carried out in plants, mainly
      due to the large unstable complexes that are hard to obtain or reconstitute in
      heterologous systems. Reconstitution of activity needs thorough understanding of
      all protein partners in the complex, something that is still an ongoing process
      in plant systems. Here, we use biochemical analysis to uncover properties of two
      previously identified native dicer-like activities from wheat germ. We find that
      standard wheat germ extract contains Dicer-like enzymes that convert double
      stranded RNA (dsRNA) into two classes of small interfering RNAs of 21 and 24 nt
      in size. The 21 nt dicing activity, likely an siRNA producing complex known as
      DCL4, is 950 kDa-1.2 mDa in size and is highly unstable during purification
      processes but has a rather vast range for activity. On the contrary, the 24 nt
      dicing complex, likely the DCL3 activity, is relatively stable and comparatively
      smaller in size, but has stricter conditions for effective processing of dsRNA
      substrates. While both activities could process completely complementary dsRNA
      albeit with varying abilities, we show that DCL3-like 24 nt producing activity is
      equally good in processing incompletely complementary RNAs. 

PMID- 25615605
TI  - Remifentanil protects human keratinocytes against hypoxia-reoxygenation injury
      through activation of autophagy.
AB  - The proliferation, differentiation, and migration of keratinocytes are essential
      in the early stages of wound healing. Hypoxia-Reoxygenation (H/R) injury to
      keratinocytes can occur in various stressful environments such as surgery,
      trauma, and various forms of ulcers. The effects of remifentanil on human
      keratinocytes under hypoxia-reoxygenation have not been fully studied. Therefore,
      we investigated the effects of remifentanil on the proliferation, apoptosis, and
      autophagic activation of human keratinocytes during hypoxic-reoxygenation. Human
      keratinocytes were cultured under 1% oxygen tension for 24 h. The cells were then
      treated with various concentrations of remifentanil (0.01, 0.1, 0.5, and 1 ng/mL)
      for 2 h. Thereafter, the cells were reoxygenated for 12 h at 37 degrees C. We
      measured cell viability via MTT assay. Using quantitative real-time PCR and
      western blot analysis, we measured the expression levels of proteins associated
      with apoptosis and autophagy. Quantification of apoptotic cells was performed
      using flow cytometer analysis and autophagic vacuoles were observed under a
      fluorescence microscope. Remifentanil treatment brought about an increase in the
      proliferation of human keratinocytes damaged by hypoxia-reoxygenation and
      decreased the apoptotic cell death, enhancing autophagic activity. However, the
      autophagy pathway inhibitor 3-MA inhibited the protective effect of remifentanil
      in hypoxia-reoxygenation injury. In conclusion, the current study demonstrated
      that remifentanil treatment stimulated autophagy and reduced apoptotic cell death
      in a hypoxia-reoxygenation model of human keratinocytes. Our results provide
      additional insights into the relationship between apoptosis and autophagy. 

PMID- 25615606
TI  - Lethality of PAK3 and SGK2 shRNAs to human papillomavirus positive cervical
      cancer cells is independent of PAK3 and SGK2 knockdown.
AB  - The p21-activated kinase 3 (PAK3) and the serum and glucocorticoid-induced kinase
      2 (SGK2) have been previously proposed as essential kinases for human
      papillomavirus positive (HPV+) cervical cancer cell survival. This was
      established using a shRNA knockdown approach. To validate PAK3 and SGK2 as
      potential targets for HPV+ cervical cancer therapy, the relationship between
      shRNA-induced phenotypes in HPV+ cervical cancer cells and PAK3 or SGK2 knockdown
      was carefully examined. We observed that the phenotypes of HPV+ cervical cancer
      cells induced by various PAK3 and SGK2 shRNAs could not be rescued by complement
      expression of respective cDNA constructs. A knockdown-deficient PAK3 shRNA with a
      single mismatch was sufficient to inhibit HeLa cell growth to a similar extent as
      wild-type PAK3 shRNA. The HPV+ cervical cancer cells were also susceptible to
      several non-human target shRNAs. The discrepancy between PAK3 and SGK2 shRNA
      induced apoptosis and gene expression knockdown, as well as cell death
      stimulation, suggested that these shRNAs killed HeLa cells through different
      pathways that may not be target-specific. These data demonstrated that HPV+
      cervical cancer cell death was not associated with RNAi-induced PAK3 and SGK2
      knockdown but likely through off-target effects. 

PMID- 25615607
TI  - Auxins differentially regulate root system architecture and cell cycle protein
      levels in maize seedlings.
AB  - Maize (Zea mays) root system architecture has a complex organization, with
      adventitious and lateral roots determining its overall absorptive capacity. To
      generate basic information about the earlier stages of root development, we
      compared the post-embryonic growth of maize seedlings germinated in water
      embedded cotton beds with that of plants obtained from embryonic axes cultivated
      in liquid medium. In addition, the effect of four different auxins, namely indole
      3-acetic acid (IAA), 1-naphthaleneacetic acid (NAA), indole-3-butyric acid (IBA)
      and 2,4-dichlorophenoxyacetic acid (2,4-D) on root architecture and levels of the
      heat shock protein HSP101 and the cell cycle proteins CKS1, CYCA1 and CDKA1 were
      analyzed. Our data show that during the first days after germination, maize
      seedlings develop several root types with a simultaneous and/or continuous
      growth. The post-embryonic root development started with the formation of the
      primary root (PR) and seminal scutellar roots (SSR) and then continued with the
      formation of adventitious crown roots (CR), brace roots (BR) and lateral roots
      (LR). Auxins affected root architecture in a dose-response fashion; whereas NAA
      and IBA mostly stimulated crown root formation, 2,4-D showed a strong repressing
      effect on growth. The levels of HSP101, CKS1, CYCA1 and CDKA in root and leaf
      tissues were differentially affected by auxins and interestingly, HSP101
      registered an auxin-inducible and root specific expression pattern. Taken
      together, our results show the timing of early branching patterns of maize and
      indicate that auxins regulate root development likely through modulation of the
      HSP101 and cell cycle proteins. 

PMID- 25615608
TI  - Allogeneic Hematopoietic Cell Transplantation for Children with Sickle Cell
      Disease Is Beneficial and Cost-Effective: A Single-Center Analysis.
AB  - Limited data exist regarding health care utilization (HCU) in patients receiving
      allogeneic hematopoietic cell transplantation (alloHCT) for sickle cell disease.
      Financial data from 2002 to 2011 were analyzed for 26 alloHCT patients and 48
      control subjects (referred but without alloHCT). HCU of alloHCT was determined
      over 3 time periods: pre-alloHCT, during alloHCT (day 0 to day +365), and post
      alloHCT. The median total cost per patient during the alloHCT year was $413,000
      inpatient and $18,000 outpatient. Post-alloHCT HCU decreased when compared with
      pre-alloHCT and control subjects. The median cost of post-alloHCT outpatient
      visits per patient was significantly less when compared with pre-alloHCT (P =
      .044). The median cost of post-alloHCT inpatient visits per patient approached
      significance when compared with those pre-alloHCT (P = .079). Sixteen post
      alloHCT patients, 19 control subjects, and 14 unaffected siblings were surveyed
      using Pediatric Quality of Life Inventory and EuroQOL questionnaires; however,
      the questionnaire scores across all 3 patient groups were not statistically
      significant (P = .2638). When adjusted for health-related quality of life, the
      analysis suggested alloHCT has a positive impact on health-related quality of
      life over control subjects. These pilot data support our hypothesis that alloHCT
      in children with sickle cell disease reduces HCU compared with control subjects
      without alloHCT. 

PMID- 25615609
TI  - "Uncovering" the recovery of natural killer cells after reduced-intensity
      conditioning transplantation.

PMID- 25615610
TI  - Terpenoids and their biosynthesis in cyanobacteria.
AB  - Terpenoids, or isoprenoids, are a family of compounds with great structural
      diversity which are essential for all living organisms. In cyanobacteria, they
      are synthesized from the methylerythritol-phosphate (MEP) pathway, using
      glyceraldehyde 3-phosphate and pyruvate produced by photosynthesis as substrates.
      The products of the MEP pathway are the isomeric five-carbon compounds
      isopentenyl diphosphate and dimethylallyl diphosphate, which in turn form the
      basic building blocks for formation of all terpenoids. Many terpenoid compounds
      have useful properties and are of interest in the fields of pharmaceuticals and
      nutrition, and even potentially as future biofuels. The MEP pathway, its function
      and regulation, and the subsequent formation of terpenoids have not been fully
      elucidated in cyanobacteria, despite its relevance for biotechnological
      applications. In this review, we summarize the present knowledge about
      cyanobacterial terpenoid biosynthesis, both regarding the native metabolism and
      regarding metabolic engineering of cyanobacteria for heterologous production of
      non-native terpenoids. 

PMID- 25615612
TI  - High density of tree-cavities and snags in tropical dry forest of western Mexico
      raises questions for a latitudinal gradient.
AB  - It has been suggested that a latitudinal gradient exists of a low density of
      snags and high density of naturally-formed tree-cavities in tropical vs.
      temperate forests, though few cavities may have characteristics suitable for
      nesting by birds. We determined snag and cavity density, characteristics, and
      suitability for birds in a tropical dry forest biome of western Mexico, and
      evaluated whether our data fits the trend of snag and cavity density typically
      found in tropical moist and wet forests. We established five 0.25-ha transects to
      survey and measure tree-cavities and snags in each of three vegetation types of
      deciduous, semi-deciduous, and mono-dominant Piranhea mexicana forest, comprising
      a total of 3.75 ha. We found a high density of 77 cavities/ha, with 37 cavities
      suitable for birds/ha, where density, and characteristics of cavities varied
      significantly among vegetation types. Lowest abundance of cavities occurred in
      deciduous forest, and these were in smaller trees, at a lower height, and with a
      narrower entrance diameter. Only 8.6% of cavities were excavated by woodpeckers,
      and only 11% of cavities were occupied, mainly by arthropods, though 52% of all
      cavities were unsuitable for birds. We also found a high density of 56 snags/ha,
      with greatest density in deciduous forest (70 snags/ha), though these were of
      significantly smaller diameter, and snags of larger diameter were more likely to
      contain cavities. The Chamela-Cuixmala tropical dry forest had the highest
      density of snags recorded for any tropical or temperate forest, and while snag
      density was significantly correlated with mean snag dbh, neither latitude nor
      mean dbh predicted snag density in ten forest sites. The high spatial aggregation
      of snag and cavity resources in tropical dry forest may limit their availability,
      particularly for large-bodied cavity adopters, and highlights the importance of
      habitat heterogeneity in providing resources for primary and secondary cavity
      nesters. 

PMID- 25615611
TI  - A large-scale seroprevalence of Epstein-Barr virus in Taiwan.
AB  - BACKGROUND: Epstein-Barr virus (EBV) causes a variety of clinical manifestations
      from asymptomatic infection to acute infectious mononucleosis in human. Moreover,
      the EBV infection is associated with malignancies. The large-scale EBV
      seroepidemiology across all age groups has been lacking in Taiwan. METHODS: A
      total of 1411 serum samples were tested to examine the seroprevalence of EBV in
      2007. The samples were collected during an island-wide seroepidemiological survey
      of vaccine preventable diseases in Taiwan. The enzyme-linked immunosorbent assay
      was performed to detect anti-EBV viral capsid IgG in sera. Demographic and
      personal health data were obtained by questionnaires. RESULTS: The overall
      weighted seropositive rate of EBV was 88.5% (95% CI, 86.7%-90.1%). The
      seropositive rate of EBV reached 52.8% (95% CI, 44.0%-61.6%) in children aged 2
      years, rapidly rose to 88.7% (95% CI, 79.0%-95.1%) in those aged 5-7 years and
      93.0% (95%CI, 83.0%-98.1%) for those aged 14-16 years. Age and higher educational
      level were associated with the increased EBV seropositive rate. CONCLUSION: In
      Taiwan, people had the EBV infection early in life. Children under 7 years should
      be the primary target popution of public health measures in the future.

PMID- 25615613
TI  - Time-dependent subcellular distribution and effects of carbon nanotubes in lungs
      of mice.
AB  - BACKGROUND AND METHODS: Pulmonary deposited carbon nanotubes (CNTs) are cleared
      very slowly from the lung, but there is limited information on how CNTs interact
      with the lung tissue over time. To address this, three different multiwalled CNTs
      were intratracheally instilled into female C57BL/6 mice: one short (850 nm) and
      tangled, and two longer (4 MUm and 5.7 MUm) and thicker. We assessed the cellular
      interaction with these CNTs using transmission electron microscopy (TEM) 1, 3 and
      28 days after instillation. RESULTS: TEM analysis revealed that the three CNTs
      followed the same overall progression pattern over time. Initially, CNTs were
      taken up either by a diffusion mechanism or via endocytosis. Then CNTs were
      agglomerated in vesicles in macrophages. Lastly, at 28 days post-exposure,
      evidence suggesting CNT escape from vesicle enclosures were found. The longer and
      thicker CNTs more often perturbed and escaped vesicular enclosures in macrophages
      compared to the smaller CNTs. Bronchoalveolar lavage (BAL) showed that the CNT
      exposure induced both an eosinophil influx and also eosinophilic crystalline
      pneumonia. CONCLUSION: Two very different types of multiwalled CNTs had very
      similar pattern of cellular interactions in lung tissue, with the longer and
      thicker CNTs resulting in more severe effects in terms of eosinophil influx and
      incidence of eosinophilic crystalline pneumonia (ECP).

PMID- 25615614
TI  - Differential requirement for irf8 in formation of embryonic and adult macrophages
      in zebrafish.
AB  - Interferon regulatory factor 8 (Irf8) is critical for mammalian macrophage
      development and innate immunity, but its role in teleost myelopoiesis remains
      incompletely understood. In particular, genetic tools to analyze the role of Irf8
      in zebrafish macrophage development at larval and adult stages are lacking. We
      generated irf8 null mutants in zebrafish using TALEN-mediated targeting. Our
      analysis defines different requirements for irf8 at different stages. irf8 is
      required for formation of all macrophages during primitive and transient
      definitive hematopoiesis, but not during adult-phase definitive hematopoiesis
      starting at 5-6 days postfertilization. At early stages, irf8 mutants have excess
      neutrophils and excess cell death in pu.1-expressing myeloid cells. Macrophage
      fates were recovered in irf8 mutants after wildtype irf8 expression in neutrophil
      and macrophage lineages, suggesting that irf8 regulates macrophage specification
      and survival. In juvenile irf8 mutant fish, mature macrophages are present, but
      at numbers significantly reduced compared to wildtype, indicating an ongoing
      requirement for irf8 after embryogenesis. As development progresses, tissue
      macrophages become apparent in zebrafish irf8 mutants, with the possible
      exception of microglia. Our study defines distinct requirement for irf8 in
      myelopoiesis before and after transition to the adult hematopoietic system. 

PMID- 25615619
TI  - Next generation sequencing of Apis mellifera syriaca identifies genes for Varroa
      resistance and beneficial bee keeping traits.
AB  - Apis mellifera syriaca exhibits a high degree of tolerance to pests and pathogens
      including varroa mites. This native honey bee subspecies of Jordan expresses
      behavioral adaptations to high temperature and dry seasons typical of the region.
      However, persistent honey bee imports of commercial breeder lines are endangering
      local honey bee population. This study reports the use of next-generation
      sequencing (NGS) technology to study the A. m. syriaca genome and to identify
      genetic factors possibly contributing toward mite resistance and other favorable
      traits. We obtained a total of 46.2 million raw reads by applying the NGS to
      sequence A. m. syriaca and used extensive bioinformatics approach to identify
      several candidate genes for Varroa mite resistance, behavioral and immune
      responses characteristic for these bees. As a part of characterizing the
      functional regulation of molecular genetic pathway, we have mapped the pathway
      genes potentially involved using information from Drosophila melanogaster and
      present possible functional changes implicated in responses to Varroa destructor
      mite infestation toward this. We performed in-depth functional annotation methods
      to identify ~600 candidates that are relevant, genes involved in pathways such as
      microbial recognition and phagocytosis, peptidoglycan recognition protein family,
      Gram negative binding protein family, phagocytosis receptors, serpins, Toll
      signaling pathway, Imd pathway, Tnf, JAK-STAT and MAPK pathway, heamatopioesis
      and cellular response pathways, antiviral, RNAi pathway, stress factors, etc.
      were selected. Finally, we have cataloged function-specific polymorphisms between
      A. mellifera and A. m. syriaca that could give better understanding of varroa
      mite resistance mechanisms and assist in breeding. We have identified immune
      related embryonic development (Cactus, Relish, dorsal, Ank2, baz), Varroa hygiene
      (NorpA2, Zasp, LanA, gasp, impl3) and Varroa resistance (Pug, pcmt, elk, elf3
      s10, Dscam2, Dhc64C, gro, futsch) functional variations genes between A.
      mellifera and A. m. syriaca that could be used to develop an effective molecular
      tool for bee conservation and breeding programs to improve locally adapted
      strains such as syriaca and utilize their advantageous traits for the benefit of
      apiculture industry. 

PMID- 25615620
TI  - Pro-inflammatory mediators increase levels of the noncoding RNA GAS5 in airway
      smooth muscle and epithelial cells.
AB  - The long noncoding RNA (lncRNA) GAS5 has been found to act as a decoy for the
      glucocorticoid receptor (GR), thus implicating GAS5 as a potential regulator of
      glucocorticoid sensitivity and resistance. Airway smooth muscle (ASM) cells and
      airway epithelial cells (AEC) play an important role in the pathogenesis and
      persistence of asthma and other chronic airways diseases. These airway structural
      cell types are also important cellular targets of the anti-inflammatory actions
      of glucocorticoids. In this study, we sought to examine the relevance of GAS5 to
      glucocorticoid sensitivity and resistance in ASM and AEC. We provide the first
      evidence that pro-inflammatory mediators up-regulate GAS5 levels in both airway
      epithelial and smooth muscle cells, and that decreasing GAS5 levels can enhance
      glucocorticoid action in AEC. 

PMID- 25615615
TI  - Antagonizing Bcl-2 family members sensitizes neuroblastoma and Ewing's sarcoma to
      an inhibitor of glutamine metabolism.
AB  - Neuroblastomas (NBL) and Ewing's sarcomas (EWS) together cause 18% of all
      pediatric cancer deaths. Though there is growing interest in targeting the
      dysregulated metabolism of cancer as a therapeutic strategy, this approach has
      not been fully examined in NBL and EWS. In this study, we first tested a panel of
      metabolic inhibitors and identified the glutamine antagonist 6-diazo-5-oxo-L
      norleucine (DON) as the most potent chemotherapeutic across all NBL and EWS cell
      lines tested. Myc, a master regulator of metabolism, is commonly overexpressed in
      both of these pediatric malignancies and recent studies have established that Myc
      causes cancer cells to become "addicted" to glutamine. We found DON strongly
      inhibited tumor growth of multiple tumor lines in mouse xenograft models. In
      vitro, inhibition of caspases partially reversed the effects of DON in high Myc
      expressing cell lines, but not in low Myc expressing lines. We further showed
      that induction of apoptosis by DON in Myc-overexpressing cancers is via the pro
      apoptotic factor Bax. To relieve inhibition of Bax, we tested DON in combination
      with the Bcl-2 family antagonist navitoclax (ABT-263). In vitro, this combination
      caused an increase in DON activity across the entire panel of cell lines tested,
      with synergistic effects in two of the N-Myc amplified neuroblastoma cell lines.
      Our study supports targeting glutamine metabolism to treat Myc overexpressing
      cancers, such as NBL and EWS, particularly in combination with Bcl-2 family
      antagonists. 

PMID- 25615621
TI  - Comparison of inverse and regular 2-pyridyl-1,2,3-triazole "click" complexes:
      structures, stability, electrochemical, and photophysical properties.
AB  - Two inverse 2-pyridyl-1,2,3-triazole "click" ligands, 2-(4-phenyl-1H-1,2,3
      triazol-1-yl)pyridine and 2-(4-benzyl-1H-1,2,3-triazol-1-yl)pyridine, and their
      palladium(II), platinum(II), rhenium(I), and ruthenium(II) complexes have been
      synthesized in good to excellent yields. The properties of these inverse "click"
      complexes have been compared to the isomeric regular compounds using a variety of
      techniques. X-ray crystallographic analysis shows that the regular and inverse
      complexes are structurally very similar. However, the chemical and physical
      properties of the isomers are quite different. Ligand exchange studies and
      density functional theory (DFT) calculations indicate that metal complexes of the
      regular 2-(1-R-1H-1,2,3-triazol-4-yl)pyridine (R = phenyl, benzyl) ligands are
      more stable than those formed with the inverse 2-(4-R-1H-1,2,3-triazol-1
      yl)pyridine (R = phenyl, benzyl) "click" chelators. Additionally, the bis-2,2'
      bipyridine (bpy) ruthenium(II) complexes of the "click" chelators have been shown
      to have short excited state lifetimes, which in the inverse triazole case,
      resulted in ejection of the 2-pyridyl-1,2,3-triazole ligand from the complex.
      Under identical conditions, the isomeric regular 2-pyridyl-1,2,3-triazole
      ruthenium(II) bpy complexes are photochemically inert. The absorption spectra of
      the inverse rhenium(I) and platinum(II) complexes are red-shifted compared to the
      regular compounds. It is shown that conjugation between the substituent group R
      and triazolyl unit has a negligible effect on the photophysical properties of the
      complexes. The inverse rhenium(I) complexes have large Stokes shifts, long metal
      to-ligand charge transfer (MLCT) excited state lifetimes, and respectable quantum
      yields which are relatively solvent insensitive. 

PMID- 25615623
TI  - VGLUT2 controls heat and punctuate hyperalgesia associated with nerve injury via
      TRPV1-Cre primary afferents.
AB  - Nerve injury induces a state of prolonged thermal and mechanical hypersensitivity
      in the innervated area, causing distress in affected individuals. Nerve injury
      induced hypersensitivity is partially due to increased activity and thereby
      sustained release of neurotransmitters from the injured fibers. Glutamate, a
      prominent neurotransmitter in primary afferents, plays a major role in
      development of hypersensitivity. Glutamate is packed in vesicles by vesicular
      glutamate transporters (VGLUTs) to enable controlled release upon depolarization.
      While a role for peripheral VGLUTs in nerve injury-induced pain is established,
      their contribution in specific peripheral neuronal populations is unresolved. We
      investigated the role of VGLUT2, expressed by transient receptor potential
      vanilloid (TRPV1) fibers, in nerve injury-induced hypersensitivity. Our data
      shows that removal of Vglut2 from Trpv1-Cre neurons using transgenic mice
      abolished both heat and punctuate hyperalgesia associated with nerve injury. In
      contrast, the development of cold hypersensitivity after nerve injury was
      unaltered. Here, we show that, VGLUT2-mediated glutamatergic transmission from
      Trpv1-Cre neurons selectively mediates heat and mechanical hypersensitivity
      associated with nerve injury. Our data clarifies the role of the Trpv1-Cre
      population and the dependence of VGLUT2-mediated glutamatergic transmission in
      nerve injury-induced hyperalgesia. 

PMID- 25615622
TI  - The Arabidopsis SWI2/SNF2 chromatin Remodeler BRAHMA regulates polycomb function
      during vegetative development and directly activates the flowering repressor gene
      SVP.
AB  - The chromatin remodeler BRAHMA (BRM) is a Trithorax Group (TrxG) protein that
      antagonizes the functions of Polycomb Group (PcG) proteins in fly and mammals.
      Recent studies also implicate such a role for Arabidopsis (Arabidopsis thaliana)
      BRM but the molecular mechanisms underlying the antagonism are unclear. To
      understand the interplay between BRM and PcG during plant development, we
      performed a genome-wide analysis of trimethylated histone H3 lysine 27 (H3K27me3)
      in brm mutant seedlings by chromatin immunoprecipitation followed by next
      generation sequencing (ChIP-seq). Increased H3K27me3 deposition at several
      hundred genes was observed in brm mutants and this increase was partially
      supressed by removal of the H3K27 methyltransferase CURLY LEAF (CLF) or SWINGER
      (SWN). ChIP experiments demonstrated that BRM directly binds to a subset of the
      genes and prevents the inappropriate association and/or activity of PcG proteins
      at these loci. Together, these results indicate a crucial role of BRM in
      restricting the inappropriate activity of PcG during plant development. The key
      flowering repressor gene SHORT VEGETATIVE PHASE (SVP) is such a BRM target. In
      brm mutants, elevated PcG occupancy at SVP accompanies a dramatic increase in
      H3K27me3 levels at this locus and a concomitant reduction of SVP expression.
      Further, our gain- and loss-of-function genetic evidence establishes that BRM
      controls flowering time by directly activating SVP expression. This work reveals
      a genome-wide functional interplay between BRM and PcG and provides new insights
      into the impacts of these proteins in plant growth and development. 

PMID- 25615625
TI  - Correction: Leukotriene Production is Increased in Abdominal Obesity.

PMID- 25615624
TI  - Statistical inference methods for two crossing survival curves: a comparison of
      methods.
AB  - A common problem that is encountered in medical applications is the overall
      homogeneity of survival distributions when two survival curves cross each other.
      A survey demonstrated that under this condition, which was an obvious violation
      of the assumption of proportional hazard rates, the log-rank test was still used
      in 70% of studies. Several statistical methods have been proposed to solve this
      problem. However, in many applications, it is difficult to specify the types of
      survival differences and choose an appropriate method prior to analysis. Thus, we
      conducted an extensive series of Monte Carlo simulations to investigate the power
      and type I error rate of these procedures under various patterns of crossing
      survival curves with different censoring rates and distribution parameters. Our
      objective was to evaluate the strengths and weaknesses of tests in different
      situations and for various censoring rates and to recommend an appropriate test
      that will not fail for a wide range of applications. Simulation studies
      demonstrated that adaptive Neyman's smooth tests and the two-stage procedure
      offer higher power and greater stability than other methods when the survival
      distributions cross at early, middle or late times. Even for proportional
      hazards, both methods maintain acceptable power compared with the log-rank test.
      In terms of the type I error rate, Renyi and Cramer-von Mises tests are
      relatively conservative, whereas the statistics of the Lin-Xu test exhibit
      apparent inflation as the censoring rate increases. Other tests produce results
      close to the nominal 0.05 level. In conclusion, adaptive Neyman's smooth tests
      and the two-stage procedure are found to be the most stable and feasible
      approaches for a variety of situations and censoring rates. Therefore, they are
      applicable to a wider spectrum of alternatives compared with other tests.

PMID- 25615626
TI  - Ratio of phosphorylated HSP27 to nonphosphorylated HSP27 biphasically acts as a
      determinant of cellular fate in gemcitabine-resistant pancreatic cancer cells.
AB  - Gemcitabine has been used most commonly as an anticancer drug to treat advanced
      pancreatic cancer patients. However, intrinsic or acquired resistance of
      pancreatic cancer to gemcitabine was also developed, which leads to very low five
      year survival rates. Here, we investigated whether cellular levels of HSP27
      phosphorylation act as a determinant of cellular fate with gemcitabine. In
      addition we have demonstrated whether HSP27 downregulation effectively could
      overcome the acquisition of gemcitabine resistance by using transcriptomic
      analysis. We observed that gemcitabine induced p38/HSP27 phosphorylation and
      caused acquired resistance. After acquisition of gemcitabine resistance, cancer
      cells showed higher activity of NF-kappaB. NF-kappaB activity, as well as colony
      formation in gemcitabine-resistant pancreatic cancer cells, was significantly
      decreased by HSP27 downregulation and subsequent TRAIL treatment, showing that
      HSP27 was a common network mediator of gemcitabine/TRAIL-induced cell death.
      After transcriptomic analysis, gene fluctuation after HSP27 downregulation was
      very similar to that of pancreatic cancer cells susceptible to gemcitabine, and
      then in opposite position to that of acquired gemcitabine resistance, which makes
      it possible to downregulate HSP27 to overcome the acquired gemcitabine resistance
      to function as an overall survival network inhibitor. Most importantly, we
      demonstrated that the ratio of phosphorylated HSP27 to nonphosphorylated HSP27
      rather than the cellular level of HSP27 itself acts biphasically as a determinant
      of cellular fate in gemcitabine-resistant pancreatic cancer cells.

PMID- 25615627
TI  - CT correlation with outcomes in 15 patients with acute Middle East respiratory
      syndrome coronavirus.
AB  - OBJECTIVE: The purpose of this article is to retrospectively analyze chest CT
      findings for 15 patients with Middle East respiratory syndrome coronavirus and to
      identify features associated with survival. MATERIALS AND METHODS: Patients were
      assigned to group 1 if they died (n=9) and to group 2 if they made a full
      recovery (n=6). Two reviewers scored chest radiographs and CT examinations for
      segmental involvement, ground-glass opacities, consolidation, and interstitial
      thickening. RESULTS: Eight patients had ground-glass opacity (53%), five had
      ground-glass and consolidation in combination (33%), five had pleural effusion
      (33%), and four patients had interlobular thickening (27%). Of 281 CT findings,
      151 (54%) were peripheral, 68 (24%) were central, and 62 (22%) had a mixed
      location. The number of involved lung segments was higher in group 1. The lower
      lobe was more commonly involved (mean, 12.2 segments) than in the upper and
      middle lobes combined (mean, 6.3 segments). The mean number of lung segments
      involved was 12.3 segments in group 1 and 3.4 segments in group 2. The CT lung
      score (mean+/-SD, 15.78+/-7.9 vs 7.3+/-5.7, p=0.003), chest radiographic score
      (20.8+/-1.7 vs 5.6+/-5.4; p=0.001), and mechanical ventilation duration (13.11+/
      8.3 vs 0.5+/-1.2 days; p=0.002) were higher in group 1. All nine group 1 patients
      and three of six group 2 patients had pleural effusion (p=0.52). CONCLUSION: CT
      of patients with Middle East respiratory syndrome coronavirus predominantly
      showed ground-glass opacities, with peripheral lower lobe preference. Pleural
      effusion and higher CT lung and chest radiographic scores correlate with poor
      prognosis and short-term mortality.

PMID- 25615629
TI  - Twelve-month results of a multicenter, blinded, pilot study of a novel peptide
      (B2A) in promoting lumbar spine fusion.
AB  - OBJECT: Failure of fusion after a transforaminal lumbar interbody fusion (TLIF)
      procedure is a challenging problem that can lead to ongoing low-back pain,
      dependence on pain medication, and inability to return to work. B2A is a
      synthetic peptide that has proven efficacy in achieving fusion in animal models
      and may have a better safety profile than bone morphogenetic protein. The authors
      undertook this study to evaluate the safety and efficacy of B2A peptide-enhanced
      ceramic granules (Prefix) in comparison with autogenous iliac crest bone graft
      (ICBG, control) in patients undergoing single-level TLIF. METHODS: Twenty-four
      patients with single-level degenerative disorders of the lumbar spine at L2-S1
      requiring TLIF were enrolled between 2009 and 2010. They were randomly assigned
      to 3 groups: a control group (treated with ICBG, n = 9), a Prefix 150 group
      (treated with Prefix 150 MUg/cm(3) granules, n = 8), and a Prefix 750 group
      (treated with Prefix 750 MUg/cm(3) granules, n = 7). Outcome measures included
      the Oswestry Disability Index (ODI), visual analog pain scale, and radiographic
      fusion as assessed by CT and dynamic flexion/extension lumbar plain radiographs.
      RESULTS: At 12 months after surgery, the radiographic fusion rate was 100% in the
      Prefix 750 group, 78% in the control group, and 50% in the Prefix 150 group,
      although the difference was not statistically significant (p = 0.08). At 6 weeks
      the mean ODI score was 41.0 for the control group, 27.7 for the Prefix 750 group,
      and 32.2 for the Prefix 150 group, whereas at 12 months the mean ODI was 24.4 for
      control, 31.1 for Prefix 750, and 29.7 for Prefix 150 groups. Complications were
      evenly distributed among the groups. CONCLUSIONS: Prefix appears to provide a
      safe alternative to autogenous ICBG. Prefix 750 appears to show superior
      radiographic fusion when compared with autograft at 12 months after TLIF,
      although no statistically significant difference was demonstrated in this small
      study. Prefix and control groups both appeared to demonstrate comparable
      improvements to ODI at 12 months.

PMID- 25615628
TI  - Sexual dimorphism in the expression of mitochondria-related genes in rat heart at
      different ages.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality worldwide.
      Moreover, sex and age are considered major risk factors in the development of
      CVDs. Mitochondria are vital for normal cardiac function, and regulation of
      mitochondrial structure and function may impact susceptibility to CVD. To
      identify potential role of mitochondria in sex-related differences in
      susceptibility to CVD, we analyzed the basal expression levels of mitochondria
      related genes in the hearts of male and female rats. Whole genome expression
      profiling was performed in the hearts of young (8-week), adult (21-week), and old
      (78-week) male and female Fischer 344 rats and the expression of 670 unique genes
      related to various mitochondrial functions was analyzed. A significant (p<0.05)
      sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in
      young, adult and old rats, respectively. Gene Ontology analysis revealed the
      influence of sex on various biological pathways related to cardiac energy
      metabolism at different ages. The expression of genes involved in fatty acid
      metabolism was significantly different between the sexes in young and adult rat
      hearts. Adult male rats also showed higher expression of genes associated with
      the pyruvate dehydrogenase complex compared to females. In young and adult
      hearts, sexual dimorphism was not noted in genes encoding oxidative
      phosphorylation. In old rats, however, a majority of genes involved in oxidative
      phosphorylation had higher expression in females compared to males. Such basal
      differences between the sexes in cardiac expression of genes associated with
      energy metabolism may indicate a likely involvement of mitochondria in
      susceptibility to CVDs. In addition, female rats showed lower expression levels
      of apoptotic genes in hearts compared to males at all ages, which may have
      implications for better preservation of cardiac mass in females than in males. 

PMID- 25615630
TI  - Cost and quality of life outcome analysis of postoperative infections after
      subaxial dorsal cervical fusions.
AB  - OBJECT: Infections following spine surgery negatively affect patient quality of
      life (QOL) and impose a significant financial burden on the health care system.
      Postoperative wound infections occur at higher rates following dorsal cervical
      procedures than ventral procedures. Quantifying the health outcomes and costs
      associated with infections following dorsal cervical procedures may help to guide
      treatment strategies to minimize the deleterious consequences of these
      infections. Therefore, the goals of this study were to determine the cost and QOL
      outcomes affecting patients who developed deep wound infections following
      subaxial dorsal cervical spine fusions. METHODS: The authors identified 22 (4.0%)
      of 551 patients undergoing dorsal cervical fusions who developed deep wound
      infections requiring surgical debridement. These patients were individually
      matched with control patients who did not develop infections. Health outcomes
      were assessed using the EQ-5D, Pain Disability Questionnaire (PDQ), Patient
      Health Questionnaire (PHQ-9), and visual analog scale (VAS). QOL outcome measures
      were collected preoperatively and after 6 and 12 months. Health resource
      utilization was recorded from patient electronic medical records over an average
      follow-up of 18 months. Direct costs were estimated using Medicare national
      payment amounts, and indirect costs were based on patients' missed workdays and
      income. RESULTS: No significant differences in preoperative QOL scores were found
      between the 2 cohorts. At 6 months postsurgery, the noninfection cohort had
      significant pre- to postoperative improvement in EQ-5D (p = 0.02), whereas the
      infection cohort did not (p = 0.2). The noninfection cohort also had a
      significantly higher 6-month postoperative EQ-5D scores than the infection cohort
      (p = 0.04). At 1 year postsurgery, there was no significant difference in EQ-5D
      scores between the groups. Health care-associated costs for the infection cohort
      were significantly higher ($16,970 vs $7658; p < 0.0001). Indirect costs for the
      infection cohort and the noninfection cohort were $6495 and $2756, respectively
      (p = 0.03). Adjusted for inflation, the total costs for the infection cohort were
      $21,778 compared with $9159 for the noninfection cohort, reflecting an average
      cost of $12,619 associated with developing a postoperative deep wound infection
      (p < 0.0001). CONCLUSIONS: Dorsal cervical infections temporarily decrease
      patient QOL postoperatively, but with no long-term impact; they do, however,
      dramatically increase the cost of care. Knowledge of the financial burden of
      wound infections following dorsal cervical fusion may stimulate the development
      and use of improved prophylactic and therapeutic techniques to manage this
      serious complication.

PMID- 25615631
TI  - Interleukin-17A gene haplotypes are associated with risk of premature coronary
      artery disease in Mexican patients from the Genetics of Atherosclerotic Disease
      (GEA) study.
AB  - AIM: The role of interleukin 17A (IL-17A) in the inflammatory process has caused
      interest in the potential significance of IL-17A as a biomarker for coronary
      artery disease (CAD). The aim of the present study was to evaluate the role of IL
      17A gene polymorphisms as susceptibility markers for CAD in the Mexican
      population. METHODS: Four IL-17A gene polymorphisms (rs8193036, rs3819024,
      rs2275913 and rs8193037) were genotyped by 5' exonuclease TaqMan assays in a
      group of 900 patients with premature CAD and 667 healthy controls (with negative
      calcium score by computed tomography), seeking associations with CAD and other
      metabolic and cardiovascular risk factors using logistic regression analyses.
      RESULTS: No single IL-17A polymorphism was associated with premature CAD, however
      two haplotypes (CAGG and TAGA) were significantly associated with increased risk
      of premature CAD (OR = 1.35, 95% CI: 1.00-1.84, P = 0.018 and OR = 2.09, 95% CI:
      1.16-3.76, P = 0.003, respectively). Moreover, rs3819024 was associated with
      increased levels of visceral abdominal fat (P = 0.002) and rs8193036 was
      significantly associated with risk of central obesity (P = 0.020),
      hypertriglyceridemia (P = 0.027), and metabolic syndrome (P = 0.027) in the
      premature CAD group, under dominant models adjusted by age, gender, BMI, smoking
      history, alcohol consumption, and treatment. CONCLUSION: The results suggest that
      IL-17A haplotypes are involved in the risk of developing premature CAD and some
      IL-17A polymorphisms are associated with cardiovascular risk factors in Mexican
      individuals with premature CAD.

PMID- 25615632
TI  - Serotonylation and Transamidation of Other Monoamines.
AB  - Although serotonin was discovered over 65 years ago, it has been only within the
      past decade that serotonin was found to be involved in a covalent post
      translational modification to proteins. The enzyme transglutaminase catalyzes the
      transamidation of serotonin to a protein-bound glutamine residue; the amino group
      of serotonin is covalently bound to the gamma carboxamide of glutamine. The term
      serotonylation is used to describe this transamidation reaction to serotonin. Not
      only can serotonin be a substrate for transamidation to proteins but also other
      monoamine neurotransmitters are substrates including histamine, dopamine, and
      noradrenaline. The term monoaminylation has been coined to describe the
      transamidation of monoamines to protein substrates. Small G proteins have emerged
      as the most common substrate for monoaminylation and are activated by this post
      translational modification. Fibronectin and cytoskeletal proteins are also
      substrates for monoaminylation. Serotonylation and monoaminylation are involved
      in a number of physiological functions, including platelet activation, insulin
      release, smooth muscle contraction, and regulation of membrane localization of
      the serotonin transporter. Stimulation of 5-HT2A receptors increases
      serotonylation and activates the small G protein Rac1, which plays a role in
      dendritic spine regulation. Monoaminylation is implicated in pathophysiological
      processes as well such as diabetes and hypertension. The availability of
      monoamines for monoaminylation is altered by antidepressants that target
      serotonin transporters, noradrenaline transporters, or the enzymatic degradation
      of monoamines as well as drugs of abuse such as cocaine and amphetamines. Further
      research on monoaminylation is needed to elucidate its physiological and
      pathophysiological roles and to explore monoaminylation as a novel target for
      drug therapy. 

PMID- 25615634
TI  - A new look.

PMID- 25615636
TI  - 2014 George M. Hollenback memorial prize for research.

PMID- 25615633
TI  - Estrogenic exposure alters the spermatogonial stem cells in the developing
      testis, permanently reducing crossover levels in the adult.
AB  - Bisphenol A (BPA) and other endocrine disrupting chemicals have been reported to
      induce negative effects on a wide range of physiological processes, including
      reproduction. In the female, BPA exposure increases meiotic errors, resulting in
      the production of chromosomally abnormal eggs. Although numerous studies have
      reported that estrogenic exposures negatively impact spermatogenesis, a direct
      link between exposures and meiotic errors in males has not been evaluated. To
      test the effect of estrogenic chemicals on meiotic chromosome dynamics, we
      exposed male mice to either BPA or to the strong synthetic estrogen, ethinyl
      estradiol during neonatal development when the first cells initiate meiosis.
      Although chromosome pairing and synapsis were unperturbed, exposed outbred CD-1
      and inbred C3H/HeJ males had significantly reduced levels of crossovers, or
      meiotic recombination (as defined by the number of MLH1 foci in pachytene cells)
      by comparison with placebo. Unexpectedly, the effect was not limited to cells
      exposed at the time of meiotic entry but was evident in all subsequent waves of
      meiosis. To determine if the meiotic effects induced by estrogen result from
      changes to the soma or germline of the testis, we transplanted spermatogonial
      stem cells from exposed males into the testes of unexposed males. Reduced
      recombination was evident in meiocytes derived from colonies of transplanted
      cells. Taken together, our results suggest that brief exogenous estrogenic
      exposure causes subtle changes to the stem cell pool that result in permanent
      alterations in spermatogenesis (i.e., reduced recombination in descendent
      meiocytes) in the adult male. 

PMID- 25615637
TI  - Dentin bonding: can we make it last?
AB  - In dentin bonding, contemporary dental adhesive systems rely on formation of the
      hybrid layer, a biocomposite containing dentin collagen and polymerized resin
      adhesive. They are usually able to create at least reasonable integrity of the
      hybrid layer with high immediate bond strength. However, loss of dentin-bonded
      interface integrity and bond strength is commonly seen after aging both in vitro
      and in vivo. This is due to endogenous collagenolytic enzymes, matrix
      metalloproteinases, and cysteine cathepsins, responsible for the time-dependent
      loss of hybrid layer collagen. In addition, the hydrophilic nature of adhesive
      systems creates problems that lead to suboptimal hybrid layers. These problems
      include, for example, insufficient resin impregnation of dentin, phase
      separation, and a low rate of polymerization, all of which may reduce the
      longevity of the bonded interface. Preservation of the collagen matrix integrity
      by inhibition of endogenous dentin proteases is key to improving dentin bonding
      durability. Several approaches to retain the integrity of the hybrid layer and to
      improve the long-term dentin bond strength have been tested. These include the
      use of enzyme inhibitors, either separately or as incorporated into the adhesive
      resins; increase of collagen resistance to enzymatic degradation; and elimination
      of water from the interface to slow down or eliminate hydrolytic loss of the
      hybrid layer components. This review looks at the principles, current status, and
      future of the different techniques designed to prevent the loss of hybrid layer
      and bond strength.

PMID- 25615639
TI  - Isolation and characterization of a "phiKMV-like" bacteriophage and its
      therapeutic effect on mink hemorrhagic pneumonia.
AB  - The objective of this study was to investigate the potential of using phages as a
      therapy against hemorrhagic pneumonia in mink both in vitro and in vivo. Five
      Pseudomonas aeruginosa (P. aeruginosa) strains were isolated from lungs of mink
      with suspected hemorrhagic pneumonia and their identity was confirmed by
      morphological observation and 16S rDNA sequence analysis. Compared to P.
      aeruginosa strains isolated from mink with hemorrhagic pneumonia in 2002, these
      isolates were more resistant to antibiotics selected. A lytic phage vB_PaeP_PPA
      ABTNL (PPA-ABTNL) of the Podoviridae family was isolated from hospital sewage
      using a P. aeruginosa isolate as host, showing broad host range against P.
      aeruginosa. A one-step growth curve analysis of PPA-ABTNL revealed eclipse and
      latent periods of 20 and 35 min, respectively, with a burst size of about 110 PFU
      per infected cell. Phage PPA-ABTNL significantly reduced the growth of P.
      aeruginosa isolates in vitro. The genome of PPA-ABTNL was 43,227 bp (62.4% G+C)
      containing 54 open reading frames and lacked regions encoding known virulence
      factors, integration-related proteins and antibiotic resistance determinants.
      Genome architecture analysis showed that PPA-ABTNL belonged to the "phiKMV-like
      Viruses" group. A repeated dose inhalational toxicity study using PPA-ABTNL crude
      preparation was conducted in mice and no significantly abnormal histological
      changes, morbidity or mortality were observed. There was no indication of any
      potential risk associated with using PPA-ABTNL as a therapeutic agent. The
      results of a curative treatment experiment demonstrated that atomization by
      ultrasonic treatment could efficiently deliver phage to the lungs of mink and a
      dose of 10 multiplicity of infection was optimal for treating mink hemorrhagic
      pneumonia. Our work demonstrated the potential for phage to fight P. aeruginosa
      involved in mink lung infections when administered by means of ultrasonic
      nebulization. 

PMID- 25615640
TI  - Simple and effective methods of freezing capercaillie (Tetrao urogallus L.)
      semen.
AB  - A continuous decline in the number and range of capercaillie (Tetrao urogallus
      L.) in many European countries can be observed, mostly due to habitat destruction
      by human activity, unecological forestry management, and increased density of
      natural predators. Ex situ in vitro gene banks provide a unique opportunity to
      preserve the genetic material for future generations. Simple and effective
      cryopreservation methods for capercaillie semen are discussed. Semen was
      collected from seven males kept in the Capercaillie Breeding Centre at Forestry
      Wisla in Poland. Within five minutes after collection, ejaculates were diluted
      with EK diluent, then divided into two parts, and subjected to two freezing
      procedures: in pellets and in straws. In fresh semen, ejaculate clearness,
      viscosity, color and volume, as well as sperm concentration, motility and
      morphology, were evaluated, while in frozen-thawed semen only motility and
      morphology of sperm were determined. Fertilizing ability of thawed semen was
      examined for samples frozen in straws. Significant (P<0.05) differences between
      individual males were found in relation to the majority of fresh semen traits:
      ejaculate volume averaged 102.1 uL (varying from 49.0 to 205.0); average sperm
      concentration was 632.5 x 106 mL-1 (178.8-1257.1); percentage of live normal
      cells varied from 39.2 to 70.3% (58.7% on an average); percentage of motile cells
      ranged from 76.0 to 85.7%) and motility parameters were male dependent, as well.
      Both cryopreservation methods had a negative effect on morphology and motility of
      frozen-thawed semen; however, the straw method yielded 60.7% and the pellet
      method 42.5% of live cells in total in thawed semen (P<0.05), while the number of
      live normal (intact) cells was similar (22.4 and 22.2%, respectively). Egg
      fertility varied between 77.8 and 91.7% (average 84.4%). Both freezing procedures
      seem to be effective in obtaining acceptable viability and high fertilizing
      potency of thawed sperm and can be used to create a gene bank of capercaillie
      semen.

PMID- 25615641
TI  - Mixture toxicity of nickel and zinc to Daphnia magna is noninteractive at low
      effect sizes but becomes synergistic at high effect sizes.
AB  - To incorporate metal mixture toxicity effects into risk-assessment procedures,
      more information is needed about combined and interactive effects of metal
      mixtures during chronic exposure. The authors investigated the toxicity of binary
      Ni-Zn mixtures in 2 independent full-factorial experiments using standard chronic
      (21-d) Daphnia magna reproduction toxicity tests. Global statistical analysis
      (i.e., when considering all investigated mixture treatments simultaneously)
      showed noninteractive effects according to the concentration addition model and
      significant synergistic effects according to the independent action model.
      However, treatment-specific statistical analysis revealed that both occurrence
      and type of interactive effect were dependent on the effect size at which Ni and
      Zn were combined in the mixture. Only noninteractive or weakly antagonistic
      effects occurred in mixture treatments in which each of the individual metals
      produced only weak adverse effects on its own (i.e., <=20% reduction of
      reproductive performance). On the other side of the spectrum, synergistic mixture
      effects occurred in all mixture treatments where both metals already caused a  >
      20% (for independent action) and a  > 40% (for concentration addition) effect on
      reproduction on their own. Because low effect sizes are the most relevant in most
      regulatory frameworks, the authors' data suggest that the concentration addition
      and independent action mixture toxicity models can both serve as conservative
      models for predicting effects of Ni-Zn mixtures. The present study highlights the
      importance of investigating metal mixture toxicity at low effect sizes and warns
      against extrapolating conclusions about metal mixture interactions from high to
      low effect sizes.

PMID- 25615642
TI  - Galnt1 is required for normal heart valve development and cardiac function.
AB  - Congenital heart valve defects in humans occur in approximately 2% of live births
      and are a major source of compromised cardiac function. In this study we
      demonstrate that normal heart valve development and cardiac function are
      dependent upon Galnt1, the gene that encodes a member of the family of
      glycosyltransferases (GalNAc-Ts) responsible for the initiation of mucin-type O
      glycosylation. In the adult mouse, compromised cardiac function that mimics human
      congenital heart disease, including aortic and pulmonary valve stenosis and
      regurgitation; altered ejection fraction; and cardiac dilation, was observed in
      Galnt1 null animals. The underlying phenotype is aberrant valve formation caused
      by increased cell proliferation within the outflow tract cushion of developing
      hearts, which is first detected at developmental stage E11.5. Developing valves
      from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1
      and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels
      of other extracellular matrix proteins. We also observed increased BMP and MAPK
      signaling. Taken together, the ablation of Galnt1 appears to disrupt the
      formation/remodeling of the extracellular matrix and alters conserved signaling
      pathways that regulate cell proliferation. Our study provides insight into the
      role of this conserved protein modification in cardiac valve development and may
      represent a new model for idiopathic valve disease. 

PMID- 25615643
TI  - Experimental study of nasopharyngeal carcinoma radionuclide imaging and therapy
      using transferred human sodium/iodide symporter gene.
AB  - PURPOSE: The aim of this study was to design a method of radionuclide for imaging
      and therapy of nasopharyngeal carcinoma (NPC) using the transferred human
      sodium/iodide symporter (hNIS) gene. METHODS: A stable NPC cell line expressing
      hNIS was established (CNE-2-hNIS). After 131I treatment, we detected
      proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the
      radioactivity of different organs of nude mice was counted and (99m)Tc imaging
      using SPECT was performed. The apparent diffusion coefficient (ADC) value changes
      of tumor xenografts were observed by diffusion-weighted magnetic resonance
      imaging (DW-MRI) within 6-24 days of 131I treatment. The correlation of ADC
      changes with apoptosis and proliferation was investigated. Post-treatment
      expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were
      detected by western blotting. RESULTS: 131I uptake was higher in CNE-2-hNIS than
      in CNE-2 cells. The proliferation and apoptosis rate decreased and increased
      respectively both in vitro and vivo in the experimental group after 131I
      treatment. The experimental group tumors accumulated (99m)Tc in vivo, leading to
      a good visualization by SPECT. DW-MRI showed that ADC values increased in the
      experimental group 6 days after treatment, while ADC values were positively and
      negatively correlated with the apoptotic and Ki-67 proliferation indices,
      respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of
      P53 and Survivin proteins and activated Caspase-3, and down-regulated the
      expression of Bcl-2 proteins. CONCLUSIONS: The radionuclide imaging and therapy
      technique for NPC hNIS-transfected cell lines can provide a new therapy strategy
      for monitoring and treatment of NPC.

PMID- 25615644
TI  - Short QTc interval in males with klinefelter syndrome-influence of CAG repeat
      length, body composition, and testosterone replacement therapy.
AB  - BACKGROUND: Klinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY)
      affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that
      electrocardiogram (ECG) abnormalities would be present in males with KS.
      OBJECTIVE: To investigate ECGs in males with KS and compare with controls.
      METHODS: Case control study of 62 males with KS and 62 healthy males matched on
      age. The primary outcome parameter was a difference in the ECG presentation
      between the two groups. The ECGs were analyzed by one blinded examiner
      (intraobserver variability 0.2-2.1%). The QT-interval was measured using "teach
      the-tangent" method excluding the U-wave. QTc was calculated using Bazett's
      equation, Hodges' equation, and a linear regression model. Body mass index,
      abdominal fat, and muscle mass as well as sex hormone levels were secondary
      parameters. The prevalence of mutations in genes related to short QT syndrome was
      determined in participants with a QTc < 330 ms. RESULTS: Compared to controls,
      the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the
      applied correction method. QTc was shortest among testosterone (T)-treated males
      with KS, while untreated and thus hypogonadal KS had QTc interval comparable to
      controls. No mutations in genes related to short QT syndrome were found.
      CONCLUSION: We found short QTc interval in males with KS, with further shortening
      of the QTc interval by T. These results suggest that genes on the X chromosome
      could be involved in regulation of the QTc interval and that T treatment may
      aggravate this mechanism.

PMID- 25615645
TI  - HSP90 inhibition suppresses lipopolysaccharide-induced lung inflammation in vivo.
AB  - Inflammation is an important component of cancer diathesis and treatment
      refractory inflammation is a feature of many chronic degenerative lung diseases.
      HSP90 is a 90kDa protein which functions as an ATP-dependent molecular chaperone
      that regulates the signalling conformation and expression of multiple protein
      client proteins especially oncogenic mediators. HSP90 inhibitors are in clinical
      development as cancer therapies but the myeleosuppressive and neutropenic effect
      of first generation geldanamycin-class inhibitors has confounded studies on the
      effects on HSP90 inhibitors on inflammation. To address this we assessed the
      ability of Ganetespib, a non-geldanamycin HSP90 blocker, to suppress
      lipopolysaccharide (LPS)-induced cellular infiltrates, proteases and inflammatory
      mediator and transcriptional profiles. Ganetespib (10-100 mg/kg, i.v.) did not
      directly cause myelosuppression, as assessed by video micrography and basal blood
      cell count, but it strongly and dose-dependently suppressed LPS-induced
      neutrophil mobilization into blood and neutrophil- and mononuclear cell-rich
      steroid-refractory lung inflammation. Ganetespib also suppressed B cell and NK
      cell accumulation, inflammatory cytokine and chemokine induction and MMP9 levels.
      These data identify non-myelosuppresssive HSP90 inhibitors as potential therapies
      for inflammatory diseases refractory to conventional therapy, in particular those
      of the lung.

PMID- 25615646
TI  - The role of fast-track surgery in pancreaticoduodenectomy: a retrospective cohort
      study of 635 consecutive resections.
AB  - BACKGROUND: Pancreaticoduodenectomy (PD) is one of the most difficult and
      dangerous operations in general surgery. This study used the concept of fast
      track surgery (FTS) technique, which involves pain control, early enteral
      nutrition and other measures during the preoperative period, to evaluate the rate
      of complications and shorter hospitalization. METHODS: This retrospective,
      observational study was conducted between January 2009 and January 2013. A total
      of 635 patients underwent PD in the Department of Pancreatic Surgery at ChangHai
      Hospital (Shanghai, China). 325 patients had FTS and 310 patients received the
      traditional pathway of treatment. The incidence of postoperative complications,
      the serum albumin level, expenses, postoperative hospitalization, and readmission
      rates were compared. RESULTS: There were no significant differences in the blood
      transfusion volume, nasogastric intubation, and readmission rates (p > 0.05).
      However, the FTS group had less postoperative hospitalization, fewer expenses and
      a lower incidence of postoperative complications compared with the control group
      (p<0.05). CONCLUSION: Pancreaticoduodenectomy can be further optimized by the use
      of FTS methods, which can reduce the incidence of in hospital postoperative
      complications and expenses without increasing the risk of readmission.

PMID- 25615647
TI  - A metacalibrated time-tree documents the early rise of flowering plant
      phylogenetic diversity.
AB  - The establishment of modern terrestrial life is indissociable from angiosperm
      evolution. While available molecular clock estimates of angiosperm age range from
      the Paleozoic to the Late Cretaceous, the fossil record is consistent with
      angiosperm diversification in the Early Cretaceous. The time-frame of angiosperm
      evolution is here estimated using a sample representing 87% of families and
      sequences of five plastid and nuclear markers, implementing penalized likelihood
      and Bayesian relaxed clocks. A literature-based review of the palaeontological
      record yielded calibrations for 137 phylogenetic nodes. The angiosperm crown age
      was bound within a confidence interval calculated with a method that considers
      the fossil record of the group. An Early Cretaceous crown angiosperm age was
      estimated with high confidence. Magnoliidae, Monocotyledoneae and
      Eudicotyledoneae diversified synchronously 135-130 million yr ago (Ma);
      Pentapetalae is 126-121 Ma; and Rosidae (123-115 Ma) preceded Asteridae (119-110
      Ma). Family stem ages are continuously distributed between c. 140 and 20 Ma. This
      time-frame documents an early phylogenetic proliferation that led to the
      establishment of major angiosperm lineages, and the origin of over half of extant
      families, in the Cretaceous. While substantial amounts of angiosperm
      morphological and functional diversity have deep evolutionary roots, extant
      species richness was probably acquired later.

PMID- 25615651
TI  - Reply to 'entropic factors also contribute to the high melting points of
      polyhedral alkanes'.

PMID- 25615648
TI  - The Moon as a recorder of organic evolution in the early solar system: a lunar
      regolith analog study.
AB  - The organic record of Earth older than ~3.8 Ga has been effectively erased. Some
      insight is provided to us by meteorites as well as remote and direct observations
      of asteroids and comets left over from the formation of the Solar System. These
      primitive objects provide a record of early chemical evolution and a sample of
      material that has been delivered to Earth's surface throughout the past 4.5
      billion years. Yet an effective chronicle of organic evolution on all Solar
      System objects, including that on planetary surfaces, is more difficult to find.
      Fortunately, early Earth would not have been the only recipient of organic matter
      containing objects in the early Solar System. For example, a recently proposed
      model suggests the possibility that volatiles, including organic material, remain
      archived in buried paleoregolith deposits intercalated with lava flows on the
      Moon. Where asteroids and comets allow the study of processes before planet
      formation, the lunar record could extend that chronicle to early biological
      evolution on the planets. In this study, we use selected free and polymeric
      organic materials to assess the hypothesis that organic matter can survive the
      effects of heating in the lunar regolith by overlying lava flows. Results
      indicate that the presence of lunar regolith simulant appears to promote
      polymerization and, therefore, preservation of organic matter. Once polymerized,
      the mineral-hosted newly formed organic network is relatively protected from
      further thermal degradation. Our findings reveal the thermal conditions under
      which preservation of organic matter on the Moon is viable.

PMID- 25615652
TI  - Entropic factors also contribute to the high melting points of polyhedral
      alkanes.

PMID- 25615653
TI  - A chemist's guide to the Solar System.

PMID- 25615659
TI  - Metallobiology: zinc differently.

PMID- 25615660
TI  - Organic cage crystals: supramolecular joinery.

PMID- 25615661
TI  - Synthetic methodology: catalytic control of chlorination.

PMID- 25615662
TI  - Proton-coupled electron transfer: metal hydrides find the sweet spot.

PMID- 25615663
TI  - Chemical biology: biosynthetic interceptors.

PMID- 25615665
TI  - Supramolecular binding and separation of hydrocarbons within a functionalized
      porous metal-organic framework.
AB  - Supramolecular interactions are fundamental to host-guest binding in many
      chemical and biological processes. Direct visualization of such supramolecular
      interactions within host-guest systems is extremely challenging, but crucial to
      understanding their function. We report a comprehensive study that combines
      neutron scattering, synchrotron X-ray and neutron diffraction, and computational
      modelling to define the detailed binding at a molecular level of acetylene,
      ethylene and ethane within the porous host NOTT-300. This study reveals
      simultaneous and cooperative hydrogen-bonding, pi...pi stacking interactions and
      intermolecular dipole interactions in the binding of acetylene and ethylene to
      give up to 12 individual weak supramolecular interactions aligned within the host
      to form an optimal geometry for the selective binding of hydrocarbons. We also
      report the cooperative binding of a mixture of acetylene and ethylene within the
      porous host, together with the corresponding breakthrough experiments and
      analysis of adsorption isotherms of gas mixtures. 

PMID- 25615664
TI  - Porphyrins at interfaces.
AB  - Porphyrins and other tetrapyrrole macrocycles possess an impressive variety of
      functional properties that have been exploited in natural and artificial systems.
      Different metal centres incorporated within the tetradentate ligand are key for
      achieving and regulating vital processes, including reversible axial ligation of
      adducts, electron transfer, light-harvesting and catalytic transformations.
      Tailored substituents optimize their performance, dictating their arrangement in
      specific environments and mediating the assembly of molecular nanoarchitectures.
      Here we review the current understanding of these species at well-defined
      interfaces, disclosing exquisite insights into their structural and chemical
      properties, and also discussing methods by which to manipulate their
      intramolecular and organizational features. The distinct characteristics arising
      from the interfacial confinement offer intriguing prospects for molecular science
      and advanced materials. We assess the role of surface interactions with respect
      to electronic and physicochemical characteristics, and describe in situ
      metallation pathways, molecular magnetism, rotation and switching. The
      engineering of nanostructures, organized layers, interfacial hybrid and bio
      inspired systems is also addressed. 

PMID- 25615667
TI  - Concerted proton-coupled electron transfer from a  metal-hydride complex.
AB  - Metal hydrides are key intermediates in the catalytic reduction of protons and
      CO2 as well as in the oxidation of H2. In these reactions, electrons and protons
      are transferred to or from separate acceptors or donors in bidirectional
      protoncoupled electron transfer (PCET) steps. The mechanistic interpretation of
      PCET reactions of metal hydrides has focused on the stepwise transfer of
      electrons and protons. A concerted transfer may, however, occur with a lower
      reaction barrier and therefore proceed at higher catalytic rates. Here we
      investigate the feasibility of such a reaction by studying the oxidation
      deprotonation reactions of a tungsten hydride complex. The rate dependence on the
      driving force for both electron transfer and proton transfer-employing different
      combinations of oxidants and bases-was used to establish experimentally the
      concerted, bidirectional PCET of a metal-hydride species. Consideration of the
      findings presented here in future catalyst designs may lead to more-efficient
      catalysts.

PMID- 25615666
TI  - Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of
      fertilization-induced zinc sparks.
AB  - Fertilization of a mammalian egg initiates a series of 'zinc sparks' that are
      necessary to induce the egg-to-embryo transition. Despite the importance of these
      zinc-efflux events little is known about their origin. To understand the
      molecular mechanism of the zinc spark we combined four physical approaches that
      resolve zinc distributions in single cells: a chemical probe for dynamic live
      cell fluorescence imaging and a combination of scanning transmission electron
      microscopy with energy-dispersive spectroscopy, X-ray fluorescence microscopy and
      three-dimensional elemental tomography for high-resolution elemental mapping. We
      show that the zinc spark arises from a system of thousands of zinc-loaded
      vesicles, each of which contains, on average, 10(6) zinc atoms. These vesicles
      undergo dynamic movement during oocyte maturation and exocytosis at the time of
      fertilization. The discovery of these vesicles and the demonstration that zinc
      sparks originate from them provides a quantitative framework for understanding
      how zinc fluxes regulate cellular processes. 

PMID- 25615668
TI  - Catalytic, stereospecific syn-dichlorination of alkenes.
AB  - As some of the oldest organic chemical reactions known, the ionic additions of
      elemental halogens such as bromine and chlorine to alkenes are prototypical
      examples of stereospecific reactions, typically delivering vicinal dihalides
      resulting from anti-addition. Although the invention of enantioselective variants
      is an ongoing challenge, the ability to overturn the intrinsic anti
      diastereospecificity of these transformations is also a largely unsolved problem.
      Here, we describe the first catalytic, syn-stereospecific dichlorination of
      alkenes, employing a group transfer catalyst based on a redox-active main group
      element (selenium). With diphenyl diselenide (PhSeSePh) (5 mol%) as the pre
      catalyst, benzyltriethylammonium chloride (BnEt3NCl) as the chloride source and
      an N-fluoropyridinium salt as the oxidant, a wide variety of functionalized
      cyclic and acyclic 1,2-disubstituted alkenes, including simple allylic alcohols,
      deliver syn-dichlorides with exquisite stereocontrol. This methodology is
      expected to find applications in streamlining the synthesis of polychlorinated
      natural products such as the chlorosulfolipids. 

PMID- 25615669
TI  - Trapping virtual pores by crystal retro-engineering.
AB  - Stable guest-free porous molecular crystals are uncommon. By contrast, organic
      molecular crystals with guest-occupied cavities are frequently observed, but
      these cavities tend to be unstable and collapse on removal of the guests-this
      feature has been referred to as 'virtual porosity'. Here, we show how we have
      trapped the virtual porosity in an unstable low-density organic molecular crystal
      by introducing a second molecule that matches the size and shape of the unstable
      voids. We call this strategy 'retro-engineering' because it parallels organic
      retrosynthetic analysis, and it allows the metastable two-dimensional hexagonal
      pore structure in an organic solvate to be trapped in a binary cocrystal. Unlike
      the crystal with virtual porosity, the cocrystal material remains single
      crystalline and porous after removal of guests by heating. 

PMID- 25615670
TI  - Rational design of functional and tunable oscillating enzymatic networks.
AB  - Life is sustained by complex systems operating far from equilibrium and
      consisting of a multitude of enzymatic reaction networks. The operating
      principles of biology's regulatory networks are known, but the in vitro assembly
      of out-of-equilibrium enzymatic reaction networks has proved challenging,
      limiting the development of synthetic systems showing autonomous behaviour. Here,
      we present a strategy for the rational design of programmable functional reaction
      networks that exhibit dynamic behaviour. We demonstrate that a network built
      around autoactivation and delayed negative feedback of the enzyme trypsin is
      capable of producing sustained oscillating concentrations of active trypsin for
      over 65 h. Other functions, such as amplification, analog-to-digital conversion
      and periodic control over equilibrium systems, are obtained by linking multiple
      network modules in microfluidic flow reactors. The methodology developed here
      provides a general framework to construct dissipative, tunable and robust
      (bio)chemical reaction networks. 

PMID- 25615671
TI  - On the origin of the stability of graphene oxide membranes in water.
AB  - Graphene oxide (GO) films are known to be highly stable in water and this
      property has made their use in membrane applications in solution possible.
      However, this state of affairs is somewhat counterintuitive because GO sheets
      become negatively charged on hydration and the membrane should disintegrate owing
      to electrostatic repulsion. We have now discovered a long-overlooked reason
      behind this apparent contradiction. Our findings show that neat GO membranes do,
      indeed, readily disintegrate in water, but the films become stable if they are
      crosslinked by multivalent cationic metal contaminants. Such metal contaminants
      can be introduced unintentionally during the synthesis and processing of GO, most
      notably on filtration with anodized aluminium oxide filter discs that corrode to
      release significant amounts of aluminium ions. This finding has wide implications
      in interpreting the processing-structure-property relationships of GO and other
      lamellar membranes. We also discuss strategies to avoid and mitigate metal
      contamination and demonstrate that this effect can be exploited to synthesize new
      membrane materials. 

PMID- 25615673
TI  - Subtle niobium.

PMID- 25615672
TI  - Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig
      cyclization.
AB  - 5-Endo-trig cyclizations are generally considered to be kinetically unfavourable,
      as described by Baldwin's rules. Consequently, observation of this mode of
      reaction under kinetic control is rare. This is usually ascribed to challenges in
      achieving appropriate approach trajectories for orbital overlap in the transition
      state. Here, we describe a highly enantio- and diastereoselective route to
      complex indanes bearing all-carbon quaternary stereogenic centres via a 5-endo
      trig cyclization catalysed by a chiral ammonium salt. Through computation, the
      preference for the formally disfavoured 5-endo-trig Michael reaction over the
      formally favoured 5-exo-trig Dieckmann reaction is shown to result from
      thermodynamic contributions to the innate selectivity of the nucleophilic group,
      which outweigh the importance of the approach trajectory as embodied by Baldwin's
      rules. Our experimental and theoretical findings demonstrate that geometric and
      stereoelectronic constraints may not be decisive in the observed outcome of
      irreversible ring-closing reactions.

PMID- 25615674
TI  - Photophysical studies of newly derivatized mono substituted phthalocyanines
      grafted onto silica nanoparticles via click chemistry.
AB  - This work reports on the synthesis, characterization and photophysical studies of
      newly derived phthalocyanine complexes and the phthalocyanine-silica
      nanoparticles conjugates. The derived phthalocyanine complexes have one terminal
      alkyne group. The derived phthalocyanine complexes showed improved photophysical
      properties (FF, FT, PhiDelta and tauT) compared to the respective phthalocyanine
      complexes from which they were derived. The derived phthalocyanine complexes were
      conjugated to the surface of an azide functionalized silica nanoparticles via
      copper (1) catalyzed cyclo-addition reaction. All the conjugates showed lower
      triplet quantum yields ranging from 0.37 to 0.44 compared to the free
      phthalocyanine complexes. The triplet lifetimes ranged from 352 to 484 MUs for
      the conjugates and from 341 to 366 MUs for the free phthalocyanine complexes.

PMID- 25615675
TI  - Selective recognition of Ni2+ ion based on fluorescence enhancement chemosensor.
AB  - A new enhancing fluorescent chemosensor was introduced for selective and
      sensitive determination of nickel ions based on 2-(1-H-benzo[d]imidazol-2yl)-N
      phenyl hydrazine carbothioamide (L). L has an intrinsic fluorescent emission
      which enhances in presence of nickel ions in CH3CN/H2O (70:30, v/v) solution. The
      fluorescence enhancement of L is attributed to a 1:1 complex formation between L
      and Ni2+ ion which has been used for selective detection of Ni2+ ion. At the
      optimum conditions, the fluorescence intensity of L at 352 nm enhances linearly
      by the concentration of nickel ion from 1.6*10(-5) to 1.6*10(-7) M and detection
      limit of 7.9*10(-8) M. The new fluorescent probe exhibited high selectivity to
      Ni2+ ion over the other common mono, di-and trivalent cations.

PMID- 25615676
TI  - Low power optical limiting studies of copper doped lithium tetraborate
      nanoparticles.
AB  - The copper doped lithium tetraborate (LTB:Cu) nanoparticles were synthesized by
      sol-gel method and characterized by XRD (tetragonal structure) and by FESEM
      (sphere-like nanoparticle). UV-Vis studies show that there is no strong
      absorption in the visible region. In the luminescence spectrum, the emission peak
      at 370 nm reveals the presence of Cu+ in LTB lattice. The relative powder second
      harmonic generation efficiency of pure and doped LTB is equal to the standard NLO
      material, KDP. The nonlinear optical parameters of LTB:Cu nanoparticles say,
      nonlinear refractive index, nonlinear absorption coefficient and third order
      nonlinear optical susceptibility were determined to be of the order of 10(
      8)cm2/W, 10(-2) cm/W and 10(-5) esu, respectively. The optical power limiting
      behavior of the samples were studied by Z-scan technique with (532 nm, 50 mW)
      Nd:YAG laser and the limiting threshold values are found to be 22.7 mW for 0.01 M
      and 24.9 mW for 0.03 and 0.05 M LTB:Cu nanoparticles.

PMID- 25615677
TI  - Optical, vibrational, NBO, first-order molecular hyperpolarizability and
      Hirshfeld surface analysis of a nonlinear optical chalcone.
AB  - The synthesis of (1E,4E)-1,5-di-p-tolylpenta-1,4-dien-3-one (DTDO) was done and
      its single crystals were grown by slow evaporation solution technique from 4
      methylbenzaldehyde, acetone solution at room temperature. Crystal structure is
      determined by single crystal X-ray diffraction analysis and reveals that it
      belongs to the monoclinic system with four molecules in the unit cell (space
      group C2). The emission of green light from the sample confirms the second
      harmonic generation (SHG) of the specimen responsible for nonlinear optical
      property. The various vibration patterns of the specimen have been investigated
      by Fourier transform infrared and Fourier transform Raman spectroscopy. Optimized
      molecular geometry, vibrational patterns of DTDO are derived from density
      functional theory (DFT) calculations and the results are compared with
      experimental one. The molecular stability and bond strengths were investigated by
      applying the natural bond orbital analysis. Information about the size, shape,
      charge density distribution and site of chemical reactivity of the molecule has
      been obtained by mapping electron density with molecular electrostatic potential
      (MEP). Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular
      orbital (LUMO) energy gaps were calculated. The other molecular properties like
      charge transfer are explained using Mulliken population analysis and the first
      order molecular hyperpolarizability (beta) of the specimen is also estimated and
      SHG efficiency of DTDO was found to be 3.9 times that of KDP. Fingerprint plots
      and Hirshfeld surfaces were used to locate and analyze the molecular surface and
      bonding interactions in various methodologies utilized in the establishment of
      the relative energies. 

PMID- 25615678
TI  - Colorimetric determination of o-phenylenediamine in water samples based on the
      formation of silver nanoparticles as a colorimetric probe.
AB  - A simple, rapid and cost-effective method for visual colorimetric detection of o
      phenylenediamine (OPD) based on the formation of silver nanoparticles (AgNPs) has
      been developed in this paper. Silver ions can be reduced to AgNPs by OPD in a few
      minutes, causing changes in absorption spectra and color of the reaction system.
      Therefore, colorimetric detection of OPD could be realized by a UV-vis
      spectrophotometer or even the naked eye. Results showed that the absorption
      intensity of AgNPs at 416 nm exhibited a good linear correlation (R2=0.998) with
      OPD concentration in the range from 10(-6) to 8*10(-5) mol L(-1) and the
      detection limit (3sigma/S) was calculated to be 1.61*10(-7) mol L(-1).
      Furthermore, as low as 4*10(-6) mol L(-1)OPD can be visualized by the naked eye
      without the requirement of any complicated or expensive instruments. This
      proposed method has been successfully applied to determine OPD in water samples,
      and may provide an innovative platform in the development of sensors for guiding
      environmental monitoring in the future.

PMID- 25615679
TI  - Assessment of conformational, spectral, antimicrobial activity, chemical
      reactivity and NLO application of Pyrrole-2,5-dicarboxaldehyde
      bis(oxaloyldihydrazone).
AB  - An orange colored pyrrole dihydrazone: Pyrrole-2,5-dicarboxaldehyde
      bis(oxaloyldihydrazone) (PDBO) has been synthesized by reaction of oxalic acid
      dihydrazide with 2,5 diformyl-1H-pyrrole and has been characterized by
      spectroscopic analysis (1H, 13C NMR, UV-visible, FT-IR and DART Mass). The
      properties of the compound has been evaluated using B3LYP functional and 6
      31G(d,p)/6-311+G(d,p) basis set. The symmetric (3319, 3320 cm(-1)) and asymmetric
      (3389, 3382 cm(-1)) stretching wave number confirm free NH2 groups in PDBO. NBO
      analysis shows, inter/intra molecular interactions within the molecule.
      Topological parameters have been analyzed by QTAIM theory and provide the
      existence of intramolecular hydrogen bonding (N-H?O). The local reactivity
      descriptors analyses determine the reactive sites within molecule. The calculated
      first hyperpolarizability value (beta0=23.83*10(-30) esu) of pyrrole dihydrazone
      shows its suitability for non-linear optical (NLO) response. The preliminary
      bioassay suggested that the PDBO exhibits relatively good antibacterial and
      fungicidal activity against Escherichia coli, Pseudomonas aeruginosa,
      Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, Aspergillus
      niger. The local reactivity descriptors--Fukui functions (fk+, fk-), local
      softnesses (sk+, sk-) and electrophilicity indices (omegak+, omegak-) analyses
      have been used to determine the reactive sites within molecule.

PMID- 25615680
TI  - Synthesis, optical properties, stability, and encapsulation of Cu-nanoparticles.
AB  - Starch-capped copper nanoparticles (CuNPs) were prepared by a chemical reduction
      method using hydrazine, copper sulfate and starch as reducing, oxidizing and
      stabilizing agents, respectively, for the first time at room temperature. The
      products were characterized by X-ray diffraction (XRD), transmission electron
      microscopy (TEM), electron diffraction patterns (EDX), X-ray photoelectron
      spectroscopy (XPS), fourier transform infrared (FT-IR) spectroscopy, thermo
      gravimetric analysis (TGA), and ultraviolet-visible spectroscopy. The effect of
      [starch], [hydrazine] and [copper sulfate] on the optical properties of CuNPs
      were studied by UV-visible spectrophotometrically. The hydrazine concentrations
      have large impact on the surface Plasmon resonance absorbance, nature of the
      reaction time curves and reaction rates decreases with [hydrazine]. Starch
      concentrations have no effect on the path of the CuNPs formation. The hexahedral
      with some irregular shaped CuNPs were formed in presence of starch with diameter
      900 nm. Starch acted as a stabilizing, shape-directing and capping agent during
      the growth processes. The KI-I2 reagent could not replace CuNps from the inner
      helical structure of starch.

PMID- 25615681
TI  - Multispectroscopic and molecular modeling studies on the interaction of two
      curcuminoids with beta-lactoglobulin.
AB  - This study demonstrates the binding properties of bisdemethoxycurcumin (BDMC) and
      diacetylbisdemethoxycurcumin (DABC) as bioactive curcuminoids with bovine beta
      lactoglobulin (BLG) variant B using fluorescence and circular dichroism (CD)
      spectroscopy; molecular docking, and molecular dynamics simulation methods. The
      estimated binding constants for BLG-BDMC and BLG-DABC complexes were (8.99+/
      0.10)*10(4) M(-1) and (1.87+/-0.10)*10(2) M(-1), respectively. The distances
      between BLG and these curcuminoids were obtained based on the Forster's theory of
      non-radiative energy transfer. Molecular docking studies revealed the binding of
      BDMC and DABC to the protein surface cleft of protein by formation of four and
      one hydrogen bonds, respectively. Finally, molecular dynamics simulation results
      represent the conformational changes of BLG due to its interaction with BDMC.
      Also, the profiles of atomic fluctuations signified the rigidity of ligand
      binding site during the simulation.

PMID- 25615682
TI  - Spectrophotometric methods for simultaneous determination of betamethasone
      valerate and fusidic acid in their binary mixture.
AB  - Five spectrophotometric methods were successfully developed and validated for the
      determination of betamethasone valerate and fusidic acid in their binary mixture.
      Those methods are isoabsorptive point method combined with the first derivative
      (ISO Point--D1) and the recently developed and well established methods namely
      ratio difference (RD) and constant center coupled with spectrum subtraction (CC)
      methods, in addition to derivative ratio (1DD) and mean centering of ratio
      spectra (MCR). New enrichment technique called spectrum addition technique was
      used instead of traditional spiking technique. The proposed spectrophotometric
      procedures do not require any separation steps. Accuracy, precision and linearity
      ranges of the proposed methods were determined and the specificity was assessed
      by analyzing synthetic mixtures of both drugs. They were applied to their
      pharmaceutical formulation and the results obtained were statistically compared
      to that of official methods. The statistical comparison showed that there is no
      significant difference between the proposed methods and the official ones
      regarding both accuracy and precision.

PMID- 25615683
TI  - A refined quartic potential energy surface and large scale vibrational
      calculations for S0 thiophosgene.
AB  - In this work we present a full 6D quartic potential energy surface (PES) for S0
      thiophosgene in curvilinear symmetrized bond-angle coordinates. The PES was
      refined starting from an ab initio field derived from acc-pVTZ basis set with
      CCSD(T) corrections for electron correlation. In the present calculations we used
      our variational method that was recently tested on formaldehyde and some of its
      isotopomers, along with additional improvements. The lower experimentally known
      vibrational levels for 35Cl2CS were reproduced quite well in the calculations,
      which can be regarded as a test for the feasibility of the obtained quartic PES.

PMID- 25615684
TI  - Different signal processing techniques of ratio spectra for spectrophotometric
      resolution of binary mixture of bisoprolol and hydrochlorothiazide; a comparative
      study.
AB  - Five signal processing techniques were applied to ratio spectra for quantitative
      determination of bisoprolol (BIS) and hydrochlorothiazide (HCT) in their binary
      mixture. The proposed techniques are Numerical Differentiation of Ratio Spectra
      (ND-RS), Savitsky-Golay of Ratio Spectra (SG-RS), Continuous Wavelet Transform of
      Ratio Spectra (CWT-RS), Mean Centering of Ratio Spectra (MC-RS) and Discrete
      Fourier Transform of Ratio Spectra (DFT-RS). The linearity of the proposed
      methods was investigated in the range of 2-40 and 1-22 MUg/mL for BIS and HCT,
      respectively. The proposed methods were applied successfully for the
      determination of the drugs in laboratory prepared mixtures and in commercial
      pharmaceutical preparations and standard deviation was less than 1.5. The five
      signal processing techniques were compared to each other and validated according
      to the ICH guidelines and accuracy, precision, repeatability and robustness were
      found to be within the acceptable limit.

PMID- 25615685
TI  - Ring closure of azo compounds to 1,2-annulated benzimidazole derivatives and
      further evidence of reversibility of the azo-coupling reaction.
AB  - The reaction between 1,3,5-tris(N,N-dialkylamino)benzene derivatives and 2 equiv
      of p-substituted benzenediazonium salts gives dicationic species which collapse
      to new benzimidazole derivatives with expulsion of p-substituted anilines. The
      presence of electron-withdrawing groups on the benzenediazo moiety of the
      dicationic species plays a key role in this unexpected ring closure reaction. The
      observed chemical behavior has been rationalized in terms of the already reported
      reversibility of azo coupling reactions and provided further evidence for it. 

PMID- 25615686
TI  - Armochaeglobines A and B, two new indole-based alkaloids from the arthropod
      derived fungus Chaetomium globosum.
AB  - Armochaeglobines A (1) and B (2), two indole-based cytochalasan alkaloids with
      new carbon skeletons, were obtained from the fungus Chaetomium globosum TW1-1,
      which was first isolated from the arthropod Armadillidium vulgare. Their
      structures were elucidated by extensive spectroscopic analyses, ECD calculation,
      and single-crystal X-ray diffraction analysis. Interestingly, compound 1 featured
      a unique tetracyclic 5/6/7/5 fused ring system and 2 possessed a rare 12-membered
      carbon scaffold. 

PMID- 25615687
TI  - Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi
      in a myoblastic cell line.
AB  - BACKGROUND: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi,
      represents a very important public health problem in Latin America where it is
      endemic. Although mostly asymptomatic at its initial stage, after the disease
      becomes chronic, about a third of the infected patients progress to a potentially
      fatal outcome due to severe damage of heart and gut tissues. There is an urgent
      need for new drugs against Chagas disease since there are only two drugs
      available, benznidazole and nifurtimox, and both show toxic side effects and
      variable efficacy against the chronic stage of the disease. METHODOLOGY/PRINCIPAL
      FINDINGS: Genetically engineered parasitic strains are used for high throughput
      screening (HTS) of large chemical collections in the search for new anti
      parasitic compounds. These assays, although successful, are limited to reporter
      transgenic parasites and do not cover the wide T. cruzi genetic background. With
      the aim to contribute to the early drug discovery process against Chagas disease
      we have developed an automated image-based 384-well plate HTS assay for T. cruzi
      amastigote replication in a rat myoblast host cell line. An image analysis script
      was designed to inform on three outputs: total number of host cells, ratio of T.
      cruzi amastigotes per cell and percentage of infected cells, which respectively
      provides one host cell toxicity and two T. cruzi toxicity readouts. The assay was
      statistically robust (Z' values >0.6) and was validated against a series of known
      anti-trypanosomatid drugs. CONCLUSIONS/SIGNIFICANCE: We have established a highly
      reproducible, high content HTS assay for screening of chemical compounds against
      T. cruzi infection of myoblasts that is amenable for use with any T. cruzi strain
      capable of in vitro infection. Our visual assay informs on both anti-parasitic
      and host cell toxicity readouts in a single experiment, allowing the direct
      identification of compounds selectively targeted to the parasite.

PMID- 25615688
TI  - Prevalence of consistent condom use with various types of sex partners and
      associated factors among money boys in Changsha, China.
AB  - INTRODUCTION: Money boys with inconsistent condom use (less than 100% of the
      time) are at high risk of infection by human immunodeficiency virus (HIV) or
      sexually transmitted infection (STI), but relatively little research has examined
      their risk behaviors. AIM: We investigated the prevalence of consistent condom
      use (100% of the time) and associated factors among money boys. METHODS: A cross
      sectional study using a structured questionnaire was conducted among money boys
      in Changsha, China, between July 2012 and January 2013. MAIN OUTCOME MEASURE:
      Independent variables included socio-demographic data, substance abuse history,
      work characteristics, and self-reported HIV and STI history. Dependent variables
      included the consistent condom use with different types of sex partners. RESULTS:
      Among the participants, 82.4% used condoms consistently with male clients, 80.2%
      with male sex partners, and 77.1% with female sex partners in the past 3 months.
      A multiple stepwise logistic regression model identified four statistically
      significant factors associated with lower likelihoods of consistent condom use
      with male clients: age group, substance abuse, lack of an "employment"
      arrangement, and having no HIV test within the prior 6 months. In a similar
      model, only one factor associated significantly with lower likelihoods of
      consistent condom use with male sex partners was identified in multiple stepwise
      logistic regression analyses: having no HIV test within the prior six months. As
      for female sex partners, two significant variables were statistically significant
      in the multiple stepwise logistic regression analysis: having no HIV test within
      the prior 6 months and having STI history. CONCLUSIONS: Interventions which are
      linked with more realistic and acceptable HIV prevention methods are greatly
      warranted and should increase risk awareness and the behavior of consistent
      condom use in both commercial and personal relationship.

PMID- 25615689
TI  - Native and dry-heated lysozyme interactions with membrane lipid monolayers: Lipid
      packing modifications of a phospholipid mixture, model of the Escherichia coli
      cytoplasmic membrane.
AB  - Antimicrobial resistance is currently an important public health issue. The need
      for innovative antimicrobials is therefore growing. The ideal antimicrobial
      compound should limit antimicrobial resistance. Antimicrobial peptides or
      proteins such as hen egg white lysozyme are promising molecules that act on
      bacterial membranes. Hen egg white lysozyme has recently been identified as
      active on Gram-negative bacteria due to disruption of the outer and cytoplasmic
      membrane integrity. Furthermore, dry-heating (7 days and 80  degrees C) improves
      the membrane activity of lysozyme, resulting in higher antimicrobial activity.
      These in vivo findings suggest interactions between lysozyme and membrane lipids.
      This is consistent with the findings of several other authors who have shown
      lysozyme interaction with bacterial phospholipids such as phosphatidylglycerol
      and cardiolipin. However, until now, the interaction between lysozyme and
      bacterial cytoplasmic phospholipids has been in need of clarification. This study
      proposes the use of monolayer models with a realistic bacterial phospholipid
      composition in physiological conditions. The lysozyme/phospholipid interactions
      have been studied by surface pressure measurements, ellipsometry and atomic force
      microscopy. Native lysozyme has proved able to absorb and insert into a bacterial
      phospholipid monolayer, resulting in lipid packing reorganization, which in turn
      has lead to lateral cohesion modifications between phospholipids. Dry-heating of
      lysozyme has increased insertion capacity and ability to induce lipid packing
      modifications. These in vitro findings are then consistent with the increased
      membrane disruption potential of dry heated lysozyme in vivo compared to native
      lysozyme. Moreover, an eggPC monolayer study suggested that lysozyme/phospholipid
      interactions are specific to bacterial cytoplasmic membranes.

PMID- 25615691
TI  - Sample size for measuring grammaticality in preschool children from picture
      elicited language samples.
AB  - PURPOSE: The purpose of this study was to investigate whether a shorter language
      sample elicited with fewer pictures (i.e., 7) would yield a percent grammatical
      utterances (PGU) score similar to that computed from a longer language sample
      elicited with 15 pictures for 3-year-old children. METHOD: Language samples were
      elicited by asking forty 3-year-old children with varying language skills to talk
      about pictures in response to prompts. PGU scores were computed for each of two 7
      picture sets and for the full set of 15 pictures. RESULTS: PGU scores for the two
      7-picture sets did not differ significantly from, and were highly correlated
      with, PGU scores for the full set and with each other. Agreement for making pass
      fail decisions between each 7-picture set and the full set and between the two 7
      picture sets ranged from 80% to 100%. CONCLUSION: The current study suggests that
      the PGU measure is robust enough that it can be computed on the basis of 7, at
      least in 3-year-old children whose language samples were elicited using similar
      procedures.

PMID- 25615690
TI  - TLR3 signaling in macrophages is indispensable for the protective immunity of
      invariant natural killer T cells against enterovirus 71 infection.
AB  - Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that
      cause hand, foot and mouth disease in children but rarely in adults. The
      mechanisms that determine the age-dependent susceptibility remain largely
      unclear. Here, we found that the paucity of invariant natural killer T (iNKT)
      cells together with immaturity of the immune system was related to the
      susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial
      antiviral effector cells to protect young mice from EV71 infection before their
      adaptive immune systems were fully mature. EV71 infection led to activation of
      iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly,
      iNKT cell activation during EV71 infection required TLR3 signaling in
      macrophages, but not in dendritic cells (DCs). Mechanistically, interleukin (IL)
      12 and endogenous CD1d-restricted antigens were both required for full activation
      of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral
      loads in central nervous system and more severe disease in EV71-infected mice.
      Altogether, our results suggest that iNKT cells may be involved in controlling
      EV71 infection in children when their adaptive immune systems are not fully
      developed, and also imply that iNKT cells might be an intervention target for
      treating EV71-infected patients. 

PMID- 25615692
TI  - A screening approach for classroom acoustics using web-based listening tests and
      subjective ratings.
AB  - BACKGROUND: Perception of speech is crucial in school where speech is the main
      mode of communication. The aim of the study was to evaluate whether a web based
      approach including listening tests and questionnaires could be used as a
      screening tool for poor classroom acoustics. The prime focus was the relation
      between pupils' comprehension of speech, the classroom acoustics and their
      description of the acoustic qualities of the classroom. METHODOLOGY/PRINCIPAL
      FINDINGS: In total, 1106 pupils aged 13-19, from 59 classes and 38 schools in
      Sweden participated in a listening study using Hagerman's sentences administered
      via Internet. Four listening conditions were applied: high and low background
      noise level and positions close and far away from the loudspeaker. The pupils
      described the acoustic quality of the classroom and teachers provided information
      on the physical features of the classroom using questionnaires.
      CONCLUSIONS/SIGNIFICANCE: In 69% of the classes, at least three pupils described
      the sound environment as adverse and in 88% of the classes one or more pupil
      reported often having difficulties concentrating due to noise. The pupils'
      comprehension of speech was strongly influenced by the background noise level
      (p<0.001) and distance to the loudspeakers (p<0.001). Of the physical classroom
      features, presence of suspended acoustic panels (p<0.05) and length of the
      classroom (p<0.01) predicted speech comprehension. Of the pupils' descriptions of
      acoustic qualities, clattery significantly (p<0.05) predicted speech
      comprehension. Clattery was furthermore associated to difficulties understanding
      each other, while the description noisy was associated to concentration
      difficulties. The majority of classrooms do not seem to have an optimal sound
      environment. The pupil's descriptions of acoustic qualities and listening tests
      can be one way of predicting sound conditions in the classroom.

PMID- 25615693
TI  - Expedited access to vinaxanthone and chemically edited derivatives possessing
      neuronal regenerative effects through ynone coupling reactions.
AB  - The natural product vinaxanthone has demonstrated a remarkable capability to
      promote nerve growth following injury or transplantation. In rats following total
      transection of the spinal cord delivery of vinaxanthone enhanced axonal
      regeneration, remyelination and angiogenesis at the site of injury all leading to
      an improved reinstatement of motor function. Through the development of a new
      ynone coupling reaction, chemically edited derivatives of vinaxanthone have been
      prepared and studied for improved activity. The coupling reaction allows rapid
      access to new derivatives, wherein n ynone precursors provide n(2) vinaxanthone
      analogues. These compounds have been tested for their ability to promote neuronal
      regrowth using laser axotomy, severing axonal connections in Caenorhabditis
      elegans. This precise microsurgery using C. elegans allows a new in vivo approach
      for medicinal chemistry based optimization of neuronal growth promoting
      compounds. 

PMID- 25615694
TI  - Catalytic efficiency of chitinase-D on insoluble chitinous substrates was
      improved by fusing auxiliary domains.
AB  - Chitin is an abundant renewable polysaccharide, next only to cellulose.
      Chitinases are important for effective utilization of this biopolymer. Chitinase
      D from Serratia proteamaculans (SpChiD) is a single domain chitinase with both
      hydrolytic and transglycosylation (TG) activities. SpChiD had less of hydrolytic
      activity on insoluble polymeric chitin substrates due to the absence of auxiliary
      binding domains. We improved catalytic efficiency of SpChiD in degradation of
      insoluble chitin substrates by fusing with auxiliary domains like polycystic
      kidney disease (PKD) domain and chitin binding protein 21 (CBP21). Of the six
      different SpChiD fusion chimeras, two C-terminal fusions viz. ChiD+PKD and
      ChiD+CBP resulted in improved hydrolytic activity on alpha- and beta-chitin,
      respectively. Time-course degradation of colloidal chitin also confirmed that
      these two C-terminal SpChiD fusion chimeras were more active than other chimeras.
      More TG products were produced for a longer duration by the fusion chimeras
      ChiD+PKD and PKD+ChiD+CBP. 

PMID- 25615695
TI  - Chromium liquid waste inertization in an inorganic alkali activated matrix:
      leaching and NMR multinuclear approach.
AB  - A class of inorganic binders, also known as geopolymers, can be obtained by
      alkali activation of aluminosilicate powders at room temperature. The process is
      affected by many parameters (curing time, curing temperature, relative humidity
      etc.) and leads to a resistant matrix usable for inertization of hazardous waste.
      In this study an industrial liquid waste containing a high amount of chromium (~
      2.3 wt%) in the form of metalorganic salts is inertized into a metakaolin based
      geopolymer matrix. One of the innovative aspects is the exploitation of the water
      contained in the waste for the geopolymerization process. This avoided any drying
      treatment, a common step in the management of liquid hazardous waste. The
      evolution of the process--from the precursor dissolution to the final geopolymer
      matrix hardening--of different geopolymers containing a waste amount ranging from
      3 to 20%wt and their capability to inertize chromium cations were studied by: i)
      the leaching tests, according to the EN 12,457 regulation, at different curing
      times (15, 28, 90 and 540 days) monitoring releases of chromium ions (Cr(III) and
      Cr(VI)) and the cations constituting the aluminosilicate matrix (Na, Si, Al); ii)
      the humidity variation for different curing times (15 and 540 days); iii) SEM
      characterization at different curing times (28 and 540 days); iv) the trend of
      the solution conductivity and pH during the leaching test; v) the
      characterization of the short-range ordering in terms of TOT bonds (where T is Al
      or Si) by (29)Si and (27)Al solid state magic-angle spinning nuclear magnetic
      resonance (ss MAS NMR) for geopolymers containing high amounts of waste (10
      20%wt). The results show the formation of a stable matrix after only 15 days
      independently on the waste amount introduced; the longer curing times increase
      the matrices stabilities and their ability to immobilize chromium cations. The
      maximum amount of waste that can be inertized is around 10 wt% after a curing
      time of 28 days.

PMID- 25615696
TI  - Structure regulation of silica nanotubes and their adsorption behaviors for heavy
      metal ions: pH effect, kinetics, isotherms and mechanism.
AB  - Silica nanotubes (SNTs) with controlled nanotubular structure were synthesized
      via an electrospinning and calcination process. In this regard, SNTs were found
      to be ideal adsorbents for Pb(II) removal with a higher adsorption capacity, and
      surface modification of the SNTs by sym-diphenylcarbazide (SD-SNTs) markedly
      enhanced the adsorption ability due to the chelating interaction between imino
      groups and Pb(II). The pH effect, kinetics, isotherms and adsorption mechanism of
      SNTs and SD-SNTs on Pb(II) adsorption were investigated and discussed detailedly.
      The adsorption capacity for Pb(II) removal was found to be significantly improved
      with the decrease of pH value. The Langmuir adsorption model agreed well with the
      experimental data. As for kinetic study, the adsorption onto SNTs and SD-SNTs
      could be fitted to pseudo-first-order and pseudo-second-order model,
      respectively. In addition, the as-prepared SNTs and SD-SNTs also exhibit high
      adsorption ability for Cd(II) and Co(II). The experimental results demonstrate
      that the SNTs and SD-SNTs are potential adsorbents and can be used effectively
      for the treatment of heavy-metal-ions-containing wastewater. 

PMID- 25615697
TI  - Genotyping of human Brucella melitensis biovar 3 isolated from Shanxi Province in
      China by MLVA16 and HOOF.
AB  - BACKGROUND: Brucellosis presents a significant economic burden for China because
      it causes reproductive failure in host species and chronic health problems in
      humans. These problems can involve multiple organs. Brucellosis is highly endemic
      in Shanxi Province China. Molecular typing would be very useful to
      epidemiological surveillance. The purpose of this study was to assess the
      diversity of Brucella melitensis strains for epidemiological surveillance.
      Historical monitoring data suggest that Brucella melitensis biovar 3 is the
      predominant strain associated with the epidemic of brucellosis in Shanxi
      Province. METHODS/PRINCIPAL FINDINGS: Multiple-locus variable-number repeat
      analysis (MLVA-16) and hypervariable octameric oligonucleotide fingerprinting
      (HOOF-print) were used to type a human-hosted Brucella melitensis population (81
      strains). Sixty-two MLVA genotypes (discriminatory index: 0.99) were detected,
      and they had a genetic similarity coefficient ranging from 84.9% to 100%. Eighty
      strains of the population belonged to the eastern Mediterranean group with panel
      1 genotypes 42 (79 strains) and 43 (1 strain). A new panel 1 genotype was found
      in this study. It was named 114 MLVAorsay genotype and it showed similarity to
      the two isolates from Guangdong in a previous study. Brucella melitensis is
      distributed throughout Shanxi Province, and like samples from Inner Mongolia, the
      eastern Mediterranean genotype 42 was the main epidemic strain (97%). The HOOF
      printing showed a higher diversity than MLVA-16 with a genetic similarity
      coefficient ranging from 56.8% to 100%. CONCLUSIONS: According to the MLVA-16 and
      HOOF-printing results, both methods could be used for the epidemiological
      surveillance of brucellosis. A new genotype was found in both Shanxi and
      Guangdong Provinces. In areas with brucellosis, the MLVA-16 scheme is very
      important for tracing cases back to their origins during outbreak investigations.
      It may facilitate the expansion and eradication of the disease.

PMID- 25615699
TI  - Copper nanoparticles of well-controlled size and shape: a new advance in
      synthesis and self-organization.
AB  - Here, we report a new synthetic route for spherical small copper nanoparticles
      (CuNPs) with size ranging from 3.5 nm to 11 nm and with an unprecedented
      associated monodispersity (<10%). This synthesis is based on the reduction of an
      organometallic precursor (CuCl(PPh3)3) by tert-butylamine borane in the presence
      of dodecylamine (DDA) at a moderate temperature (50 to 100  degrees C). Because
      of their narrow size distribution, the CuNPs form long-range 2D organizations
      (several MUm(2)). The wide range of CuNPs sizes is obtained by controlling the
      reaction temperature and DDA-to-copper phosphine salt ratio during the synthesis
      process. The addition of oleic acid (OA) after the synthesis stabilizes the CuNPs
      (no coalescence) for several weeks under a nitrogen atmosphere. The nature and
      the reactivity of the ligands were studied by IR and UV-visible spectroscopy. We
      thus show that just after synthesis the nanoparticles are coated by phosphine and
      DDA. After adding OA, a clear exchange between phosphine and OA is evidenced.
      This exchange is possible thanks to an acid-base reaction between the free
      alkylamine in excess in the solution and OA. OA is then adsorbed on the NPs
      surface in the form of carboxylate. Furthermore, the use of oleylamine (OYA)
      instead of DDA as the capping agent allows one to obtain other NP shapes
      (nanorods, triangles and nanodisks). We get evidence that OYA allows the
      selective adsorption of chloride ions derived from the copper precursor on the
      different crystallographic faces during the growth of CuNPs that induces the
      formation of anisotropic shapes such nanorods or triangles. 

PMID- 25615698
TI  - Fibroblast growth factor receptor 2 (FGFR2) is required for corneal epithelial
      cell proliferation and differentiation during embryonic development.
AB  - Fibroblast growth factors (FGFs) play important roles in many aspects of
      embryonic development. During eye development, the lens and corneal epithelium
      are derived from the same surface ectodermal tissue. FGF receptor (FGFR)
      signaling is essential for lens cell differentiation and survival, but its role
      in corneal development has not been fully investigated. In this study, we
      examined the corneal defects in Fgfr2 conditional knockout mice in which Cre
      expression is activated at lens induction stage by Pax6 P0 promoter. The cornea
      in LeCre, Fgfr2(loxP/loxP) mice (referred as Fgfr2(CKO)) was analyzed to assess
      changes in cell proliferation, differentiation and survival. We found that
      Fgfr2(CKO) cornea was much thinner in epithelial and stromal layer when compared
      to WT cornea. At embryonic day 12.5-13.5 (E12.5-13.5) shortly after the lens
      vesicle detaches from the overlying surface ectoderm, cell proliferation (judged
      by labeling indices of Ki-67, BrdU and phospho-histone H3) was significantly
      reduced in corneal epithelium in Fgfr2(CKO) mice. At later stage, cell
      differentiation markers for corneal epithelium and underlying stromal mesenchyme,
      keratin-12 and keratocan respectively, were not expressed in Fgfr2(CKO) cornea.
      Furthermore, Pax6, a transcription factor essential for eye development, was not
      present in the Fgfr2(CKO) mutant corneal epithelial at E16.5 but was expressed
      normally at E12.5, suggesting that FGFR2-signaling is required for maintaining
      Pax6 expression in this tissue. Interestingly, the role of FGFR2 in corneal
      epithelial development is independent of ERK1/2-signaling. In contrast to the
      lens, FGFR2 is not required for cell survival in cornea. This study demonstrates
      for the first time that FGFR2 plays an essential role in controlling cell
      proliferation and differentiation, and maintaining Pax6 levels in corneal
      epithelium via ERK-independent pathways during embryonic development.

PMID- 25615700
TI  - Microbial strategies for antagonizing Toll-like-receptor signal transduction.
AB  - Within a few years of the discovery of Toll-like receptors (TLRs) and their role
      in innate immunity, viral and bacterial proteins were recognized to antagonize
      TLR signal transduction. Since then, as TLR signaling networks were unraveled,
      microbial systems have been discovered that target nearly every component within
      these pathways. However, recent findings as well as some notable exceptions
      promote the idea that more of these systems have yet to be discovered. For
      example, we know very little about microbial systems for directly targeting non
      cytoplasmic portions of TLR signaling pathways, that is, the ligand interacting
      portions of the receptor itself. In this review, we compare and contrast
      strategies by which bacteria and viruses antagonize TLR signaling networks to
      identify potential areas for future research. 

PMID- 25615702
TI  - Heat-precipitation allows the efficient purification of a functional plant
      derived malaria transmission-blocking vaccine candidate fusion protein.
AB  - Malaria is a vector-borne disease affecting more than two million people and
      accounting for more than 600,000 deaths each year, especially in developing
      countries. The most serious form of malaria is caused by Plasmodium falciparum.
      The complex life cycle of this parasite, involving pre-erythrocytic, asexual and
      sexual stages, makes vaccine development cumbersome but also offers a broad
      spectrum of vaccine candidates targeting exactly those stages. Vaccines targeting
      the sexual stage of P. falciparum are called transmission-blocking vaccines
      (TBVs). They do not confer protection for the vaccinated individual but aim to
      reduce or prevent the transmission of the parasite within a population and are
      therefore regarded as an essential tool in the fight against the disease. Malaria
      predominantly affects large populations in developing countries, so TBVs need to
      be produced in large quantities at low cost. Combining the advantages of
      eukaryotic expression with a virtually unlimited upscaling potential and a good
      product safety profile, plant-based expression systems represent a suitable
      alternative for the production of TBVs. We report here the high level (300 MUg/g
      fresh leaf weight (FLW)) transient expression in Nicotiana benthamiana leaves of
      an effective TBV candidate based on a fusion protein F0 comprising Pfs25 and the
      C0-domain of Pfs230, and the implementation of a simple and cost-effective heat
      treatment step for purification that yields intact recombinant protein at >90%
      purity with a recovery rate of >70%. The immunization of mice clearly showed that
      antibodies raised against plant-derived F0 completely blocked the formation of
      oocysts in a malaria transmission-blocking assay (TBA) making F0 an interesting
      TBV candidate or a component of a multi-stage malaria vaccine cocktail.

PMID- 25615701
TI  - Innate lymphoid cells: new insights into function and development.
AB  - Here, we illustrate the complexity of ILC subsets and discuss novel functions,
      focusing on emerging mechanisms of crosstalk with other immune cells and the
      microbiota. Furthermore, we highlight recent insights into the development of
      ILCs, including the common pathways they share as well as points of divergence
      between ILC groups and subsets. 

PMID- 25615703
TI  - Environmental Correlates of Recreational Walking in the Neighborhood.
AB  - PURPOSE: To assess environmental correlates of neighborhood recreational walking.
      DESIGN: The study used a cross-sectional survey. SETTING: The study was conducted
      in the local community. SUBJECTS: Participants were adults who recently relocated
      and walk for recreation in their current neighborhood. MEASURES: The outcome
      measure was participant-reported neighborhood recreational walking in
      participants' prior neighborhood. Exposure measures were (1) participant-reported
      social and environmental characteristics of the prior neighborhood and (2)
      geographic information system-derived environmental characteristics assessed
      within a buffer around participant's prior address. ANALYSIS: Participants
      reporting current neighborhood recreational walking (n = 231) were characterized
      by whether they walked for recreation in their prior neighborhood. Associations
      between neighborhood characteristics and neighborhood recreational walking were
      assessed using logistic regression. RESULTS: Neighborhood recreational walking
      was associated with perceptions of the presence of recreational facilities (odds
      ratio [OR] = 2.49, 95% confidence interval [CI] = 1.29-4.84), interesting things
      to see (OR = 2.82, 95% CI = 1.46-5.45), and others being active (OR = 3.56, 95%
      CI = 1.80-7.05), and was inversely associated with concerns about crime (OR =
      .40, 95% CI = .20-.77) and traffic (OR = .43, 95% CI = .22-.87). This behavior
      was associated with objectively measured presence of walking trails (OR = 3.58,
      95% CI = 1.07-4.46), percentage of street length with speed limits <=25 mph (OR =
      1.31 for 10% increase, 95% CI = 1.08-1.61), and percentage of tree canopy
      coverage (OR = 1.55 for 10% increase, 95% CI = 1.12-2.14). CONCLUSION:
      Recreational walking may be influenced by environmental factors that support a
      safe, enjoyable, and social experience, attributes that are not necessarily
      prioritized in transportation walking. Outcome and exposure specificity are
      important when studying recreational walking.

PMID- 25615704
TI  - Depressive symptoms mediate the association between fear of crime and higher body
      mass index.
AB  - PURPOSE: To investigate pathways in the association between fear of crime and
      obesity. DESIGN: A cross-sectional survey was administered among residents aged
      18 years and older across all Census tracts. SETTING: Genesee County, Michigan.
      SUBJECTS: A total of 3192 residents. MEASURES: Body mass index (BMI) was
      calculated by using the respondents' reported height and weight. Composite fear
      of-crime and depressive symptoms scores were calculated by using several survey
      items. ANALYSIS . Path analysis examined the effects of fear of crime on BMI.
      RESULTS . Fear of crime was associated with higher BMI. Depressive symptoms
      mediated the relationship between fear of crime and BMI (p < .001). Moderate
      exercise mediated the association between depressive symptoms and BMI (p < .001).
      CONCLUSION: Fear of crime was associated with depressive symptoms, which in turn
      were associated with reduced exercise and subsequently higher BMI.

PMID- 25615705
TI  - Facilitators and barriers to using treadmill workstations under real working
      conditions: a qualitative study in female office workers.
AB  - PURPOSE: Characterize barriers and facilitators to use treadmill workstations in
      real work sites. DESIGN: For 6 months, workers tried a sit-stand-walk treadmill
      workstation at will with expert ergonomic support. Qualitative data were
      collected monthly. SETTING: Administrative and academic departments at a higher
      education institution in Massachusetts, United States. PARTICIPANTS: Five female
      administrative office workers. METHOD: One monthly group interview and one
      personal interview per participant during 6 months. Emerging topics from previous
      interviews were used in successive data gatherings. Transcribed data were
      manually coded according to the predefined topics of usability, comfort, safety,
      and productivity. RESULTS: The setup of the work station, communication
      difficulties while walking (disrespectful, noisy), and peer pressure to maximize
      use were the main usability barriers. There was no event of falls. Trips were
      minimized. About comfort, subjects reported it hard to get used to prolonged
      standing position during the first month. Treadmill speed affected productivity
      mostly while drawing and working in spreadsheets. Lack of job autonomy was
      revealed as a generic barrier. CONCLUSION: In this female group, treadmill
      workstations had serious design problems for workers with not enough control of
      their jobs. The early identification and removal of barriers likely needs to be
      considered when offering these workstations to workers with low job autonomy.

PMID- 25615706
TI  - Regular Exercise Throughout Pregnancy Is Associated With a Shorter First Stage of
      Labor.
AB  - PURPOSE: The aim of the present study was to examine the influence of moderate
      physical exercise throughout pregnancy on the duration of labor stages. DESIGN:
      Study was a randomized controlled trial. SETTING: The study took place at
      Hospital Puerta de Hierro and Hospital Severo Ochoa in Madrid, Spain. SUBJECTS:
      We examined 166 pregnant women (31.6 +/- 3.8 years), and all had uncomplicated
      and singleton gestation. Of these 83 were allocated to the exercise group (EG)
      and 83 to the control group (CG). INTERVENTION: Women from the EG participated in
      a physical conditioning program throughout pregnancy, which included 55- to 60
      minute sessions, 3 days per week. MEASURES: Pregnancy outcomes were measured:
      duration of labor stages, gestational age, weight gain, type of delivery, birth
      weight, birth size, head circumference, Apgar score, pH of umbilical cord.
      ANALYSIS: Student's unpaired t-tests and chi(2) tests were used; p values of <
      .05 indicated statistical significance. Cohen's d was used to determine the
      effect size. RESULTS: Significant differences were found in the duration of the
      first stage of labor (EG = 389.6 +/- 347.64 minutes vs. CG = 515.72 +/- 353.36
      minutes; p = .02, effect size Cohen's d = .36). The second and third stages did
      not differ between the study groups. CONCLUSION: A physical exercise program
      during pregnancy is associated with a shorter first stage of labor. These results
      may have important relevance to public health.

PMID- 25615707
TI  - FUEL Your Life: A Translation of the Diabetes Prevention Program to Worksites.
AB  - PURPOSE: To evaluate the effectiveness of FUEL Your Life, a translation of the
      Diabetes Prevention Program for worksites. DESIGN: A randomized control group
      design was conducted in five worksites of a large transportation company.
      Measures were collected pretest, posttest (6 months), and follow-up (12 months).
      SETTING: Railroad maintenance facilities of Union Pacific Railroad. SUBJECTS:
      Participants consisted of 362 workers (227 treatment, 135 control). INTERVENTION:
      FUEL Your Life was translated from the Diabetes Prevention Program to better fit
      within the context of the worksite. The primary difference was the use of peer
      health coaches to provide social support and reinforcement and an occupational
      nurse to provide lesson content (six sessions of 10 minutes) to participants
      instead of the lifestyle coaches employed by the Diabetes Prevention Program,
      resulting in a less structured meeting schedule. MEASURES: The primary outcomes
      were weight and body mass index (BMI), with secondary outcomes including eating
      behaviors, physical activity, and social support. ANALYSIS: Latent growth
      modeling was used to measure changes in the outcomes over time. RESULTS:
      Participants in the intervention group maintained weight/BMI (-.1 pounds/-.1
      BMI), whereas the control participants gained weight/BMI (+2.6 pounds/+.3 BMI),
      resulting in a statistically significant difference between groups. Fifty-five
      percent of intervention participants lost some weight, whereas only 35% of the
      control group lost weight. CONCLUSIONS: FUEL Your Life, a low intensity
      intervention, was not effective for promoting weight loss, but was effective for
      helping workers maintain weight over a 12-month period.

PMID- 25615708
TI  - Randomized controlled trial of storytelling compared to a personal risk tool
      intervention on colorectal cancer screening in low-income patients.
AB  - PURPOSE: Screening rates for colorectal cancer (CRC) lag for low-income, minority
      populations, contributing to poorer survival rates. A model of storytelling as
      culture-centric health promotion was tested for promoting CRC screening. DESIGN:
      A two-group parallel randomized controlled trial. SETTING: Primary care, safety
      net clinics. SUBJECTS: Low-income patients due for CRC screening, ages 50 to 75
      years, speaking English or Spanish. INTERVENTION: Patients were exposed to either
      a video created from personal stories composited into a drama about "Papa"
      receiving CRC screening, or an instrument estimating level of personal cancer
      risk. Patients received a health care provider referral for CRC screening and
      were followed up for 3 months to document adherence. MEASURES: Behavioral factors
      related to the narrative model (identification and engagement) and theory of
      planned behavior. ANALYSIS: Main effects of the interventions on screening were
      tested, controlling for attrition factors, and demographic factor associations
      were assessed. Path analysis with model variables was used to test the direct
      effects and multiple mediator models. RESULTS: Main effects on CRC screening
      (roughly half stool-based tests, half colonoscopy) did not indicate significant
      differences (37% and 42% screened for storytelling and risk-based messages,
      respectively; n = 539; 33.6% male; 62% Hispanic). Factors positively associated
      with CRC screening included being female, Hispanic, married or living with a
      partner, speaking Spanish, having a primary care provider, lower income, and no
      health insurance. Engagement, working through positive attitudes toward the
      behavior, predicted CRC screening. CONCLUSION: A storytelling and a personalized
      risk-tool intervention achieved similar levels of screening among
      unscreened/underscreened, low-income patients. Factors usually associated with
      lower rates of screening (e.g., no insurance, being Hispanic) were related to
      more adherence. Both interventions' engagement factor facilitated positive
      attitudes about CRC screening associated with behavior change.

PMID- 25615709
TI  - A qualitative evaluation of patient-perceived benefits and barriers to
      participation in a telephone care management program.
AB  - PURPOSE: To examine why high-risk individuals targeted for a telephone care
      management program participated at low rates. DESIGN: Study design consisted of
      qualitative, semistructured interviews. SETTING: The setting was a large national
      insurer's telephone-based care management program. The program employed
      registered nurses to provide individually tailored education and counseling about
      health and health care. SUBJECTS: Study subjects comprised members of a national
      insurer who were recruited to participate in a care management program but had
      either dropped out of the program after a short period of initial engagement or
      had never participated despite recruitment efforts. MEASURES: Interview content
      was divided into four categories: knowledge of the case management program,
      barriers to program participation, perceptions of benefits of the program, and
      suggestions for program improvement. ANALYSIS: Investigators conducted a directed
      content analysis. RESULTS: The most commonly cited barriers to participation were
      a lack of perceived need and a sense of distrust toward the program and its
      staff. The most commonly cited benefits were psychosocial support and goal
      setting. CONCLUSION: Care management programs may benefit from changes to how
      insurance plan members are selected for the program and from adjusting program
      content to address perceived needs among members.

PMID- 25615710
TI  - Sialidase inhibition to increase platelet counts: A new treatment option for
      thrombocytopenia.

PMID- 25615711
TI  - Molecular mechanism of cell death induced by king cobra (Ophiophagus hannah)
      venom l-amino acid oxidase.
AB  - Snake venom LAAOs have been reported to exhibit a wide range of pharmacological
      activities, including cytotoxic, edema-inducing, platelet aggregation
      inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities.
      A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus
      hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity
      against human tumorigenic cells but not in their non-tumorigenic counterparts,
      and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In
      this work, the molecular mechanism of cell death induced by OH-LAAO was
      investigated. The enzyme exerts its apoptosis-inducing effect presumably via both
      intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9
      activities. Oligonucleotide microarray analysis showed that the expression of a
      total of 178 genes was significantly altered as a result of oxidative stress
      induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at
      least 27 genes are involved in apoptosis and cell death. These alterations of
      gene expression was presumably caused by the direct cytotoxic effect of H2O2
      generated during the enzymatic reaction, as well as the non-specific oxidative
      modifications of signaling molecules that eventually lead to apoptosis and cell
      death. The very substantial up-regulation of cytochrome P450 genes may also
      contribute to the potent cytotoxic action of OH-LAAO by producing excessive
      reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing
      activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2
      generated during the enzymatic reaction, as well as the non-specific oxidation of
      signalling molecules. 

PMID- 25615712
TI  - Calculation of substructural analysis weights using a genetic algorithm.
AB  - This work describes a genetic algorithm for the calculation of substructural
      analysis for use in ligand-based virtual screening. The algorithm is simple in
      concept and effective in operation, with simulated virtual screening experiments
      using the MDDR and WOMBAT data sets showing it to be superior to substructural
      analysis weights based on a naive Bayesian classifier. 

PMID- 25615713
TI  - Randoms and TOF gain revisited.
AB  - Time-of-flight (TOF) positron emission tomography (PET) typically reduces the
      variance in the images by a factor that is proportional to the size of the object
      to be scanned, and inversely proportional to the time resolution of the PET
      scanner. Attempts to better characterize this relationship and understand its
      limits have been published, showing that such gain also increases with random
      fraction. In this paper, new experimental and simulated data are analyzed and old
      results are incorporated in the study. The proportionality of TOF gain with time
      resolution is confirmed, the proportionality constant is measured, the effect of
      the randoms is validated, and the limit of the model for small objects is
      investigated. 

PMID- 25615714
TI  - Coalesced poly(epsilon-caprolactone) fibers are stronger.
AB  - Melt-spun fibers were made from poly(epsilon-caprolactone) (PCL) coalesced from
      stoichiometric inclusion complex crystals formed with host urea. Melting and
      crystallization behaviors, mechanical properties, and the birefringence of
      undrawn and cold-drawn fibers were investigated. Undrawn coalesced PCL fibers
      were observed to have 500-600% higher moduli than undrawn as-received (asr) PCL
      fibers and a modulus comparable to drawn asr PCL fibers. Drawn coalesced PCL
      fibers have the highest crystallinity, orientation, and 65% higher moduli than
      drawn asr PCL fibers. Drawn coalesced PCL fibers have only a 5% higher
      crystallinity than drawn asr PCL fibers, yet they have 65% higher moduli and
      lower elongation at break values. Clearly, the intrinsic alignment of the
      coalesced polymers is the reason for their higher moduli and lower elongation, as
      confirmed by the birefringence observed in drawn coalesced and asr-PCL fibers.
      The improved mechanical properties of coalesced PCL fibers make them a better
      candidate for use in tissue engineering as scaffolds. 

PMID- 25615715
TI  - Exchange transfusion in patients with Down syndrome and severe transient
      leukemia.
AB  - BACKGROUND: Among neonates with Down syndrome (DS) and transient leukemia (TL),
      hyperleukocytosis (white blood cell [WBC] count >100 * 10(9) /L) is associated
      with increased blood viscosity, respiratory failure due to pulmonary
      hypertension, multiorgan failure, and increased risk of early death. There have
      been no previous studies focusing on the effects of exchange transfusion (ExT) on
      WBC count, respiratory status, and other parameters in TL patients with
      hyperleukocytosis. METHODS: An observational retrospective study was carried out
      at a single center of all five DS neonates with TL, GATA1 mutations, and
      hyperleukocytosis, born at a median gestational age of 34 weeks (range, 30-38
      weeks) with birthweight 2556 g (range, 1756-3268 g) during a 24 month study
      period between September 2011 and August 2013. All five neonates underwent ExT at
      a median age of 2 days (range, 0-5 days) before initiation of other cytoreductive
      therapy with cytarabine, which was carried out in two patients. RESULTS: All
      patients required respiratory support before ExT. After ExT, respiration status
      improved in all five patients: WBC count (mean) decreased by 85% from 143 * 10(9)
      /L to 21 * 10(9) /L. None developed tumor lysis syndrome. Three survived and two
      died: one hydrops fetalis neonate born at gestational week 30 died at age 5 days,
      and another died eventually from acute gastroenteritis 40 days after leaving
      hospital at the age of 155 days with complete remission. Two of the three
      surviving neonates developed acute megakaryocytic leukemia at age 90 days and 222
      days. CONCLUSION: ExT was very effective in improving hyperleukocytosis and may
      have had favorable effects on respiration.

PMID- 25615716
TI  - The impact of molecular dynamics on drug design: applications for the
      characterization of ligand-macromolecule complexes.
AB  - Among all tools available to design new drugs, molecular dynamics (MD)
      simulations have become an essential technique. Initially developed to
      investigate molecular models with a limited number of atoms, computers now enable
      investigations of large macromolecular systems with a simulation time reaching
      the microsecond range. The reviewed articles cover four years of research to give
      an overview on the actual impact of MD on the current medicinal chemistry
      landscape with a particular emphasis on studies of ligand-protein interactions.
      With a special focus on studies combining computational approaches with data
      gained from other techniques, this review shows how deeply embedded MD
      simulations are in drug design strategies and articulates what the future of this
      technique could be. 

PMID- 25615717
TI  - In situ normoxia enhances survival and proliferation rate of human adipose tissue
      derived stromal cells without increasing the risk of tumourigenesis.
AB  - Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low
      oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension
      (i.e., in situ normoxia), has been known to enhance the growth and survival rate
      of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we
      investigated the tumourigenic potential of ASCs under their physiological
      condition to ensure their safe use in regenerative therapy. Human ASCs isolated
      from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or
      in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri
      lineage differentiation potential, and self-renewal properties under in situ
      normoxia without altering their morphology. In situ normoxia displayed a higher
      proliferation and viability of ASCs with less DNA damage as compared to
      atmospheric O2 concentration. Moreover, low oxygen tension significantly up
      regulated VEGF and bFGF mRNA expression and protein secretion while reducing the
      expression level of tumour suppressor genes p16, p21, p53, and pRb. However,
      there were no significant differences in ASCs telomere length and their relative
      telomerase activity when cultured at different oxygen concentrations.
      Collectively, even with high proliferation and survival rate, ASCs have a low
      tendency of developing tumour under in situ normoxia. These results suggest 2% O2
      as an ideal culture condition for expanding ASCs efficiently while maintaining
      their characteristics. 

PMID- 25615719
TI  - Comparison of four rapid diagnostic tests, ELISA, microscopy and PCR for the
      detection of Giardia lamblia, Cryptosporidium spp. and Entamoeba histolytica in
      feces.
AB  - PURPOSE: Microscopy is the diagnostic reference standard for the detection of
      parasites, but it is labor-intensive and requires experience. Rapid diagnostic
      tests (RDTs) can provide an alternative to microscopy. METHODS: RDTs from four
      different manufacturers were compared to enzyme-linked immunosorbent assay
      (ELISA), microscopy and/or parasite-specific real-time PCR: ImmunoCardSTAT!(r)CGE
      (Meridian Bioscience Inc., Cincinnati, Ohio, USA) (A), Crypto/Giardia Duo-Strip
      (Coris Bioconcepts, Gembloux, Belgium) (B), RIDA(r)QUICK
      Cryptosporidium/Giardia/Entamoeba Combi (R-BioPharm, Darmstadt, Germany) (C) and
      Giardia/Cryptosporidium Quik Chek (Techlab Inc., Blacksburg, Virginia, USA) (D).
      RESULTS: Thirty frozen samples were analyzed retrospectively. For Giardia lamblia
      (n=12) and Cryptosporidium (n=12) sensitivities ranged from 58% (B), over 83% (A,
      C) to 100% (D) and from 92% (B) to 100% (A, C, D), respectively. Specificity for
      both G. lamblia and Cryptosporidium was 100% for all RDT brands. Sensitivity for
      Entamoeba histolytica (n=5) was 100%, while specificity reached 80% (A) to 88%
      (C). In a prospective study, fresh samples were tested. For G. lamblia (n=30),
      sensitivity ranged from 66% (B), over 79% (A) and 83% (C) to 100% (D) and
      specificity varied between 94% (D) and 100% (A, B, C). For Cryptosporidium (n=3),
      sensitivity was 100% for all brands except (B) (67%) and specificities were 95%
      (A, B), 98% (C) and 100% (D). E. histolytica (n=1) was detected by both (A) and
      (C), while specificity was 81% and 87% respectively. CONCLUSION: RDTs can be a
      valuable tool when microscopic expertise is poor and in remote and outbreak
      settings where other techniques are often not available and rapid diagnosis is
      required.

PMID- 25615720
TI  - Oxidative damage in DNA bases revealed by UV resonant Raman spectroscopy.
AB  - We report on the use of the UV Raman technique to monitor the oxidative damage of
      deoxynucleotide triphosphates (dATP, dGTP, dCTP and dTTP) and DNA (plasmid
      vector) solutions. Nucleotide and DNA aqueous solutions were exposed to hydrogen
      peroxide (H2O2) and iron containing carbon nanotubes (CNTs) to produce Fenton's
      reaction and induce oxidative damage. UV Raman spectroscopy is shown to be
      maximally efficient to reveal changes in the nitrogenous bases during the
      oxidative mechanisms occurring on these molecules. The analysis of Raman spectra,
      supported by numerical computations, revealed that the Fenton's reaction causes
      an oxidation of the nitrogenous bases in dATP, dGTP and dCTP solutions leading to
      the production of 2-hydroxyadenine, 8-hydroxyguanine and 5-hydroxycytosine. No
      thymine change was revealed in the dTTP solution under the same conditions.
      Compared to single nucleotide solutions, plasmid DNA oxidation has resulted in
      more radical damage that causes the breaking of the adenine and guanine aromatic
      rings. Our study demonstrates the advantage of using UV Raman spectroscopy for
      rapidly monitoring the oxidation changes in DNA aqueous solutions that can be
      assigned to specific nitrogenous bases. 

PMID- 25615718
TI  - Quantitative chemical exchange saturation transfer (qCEST) MRI - omega plot
      analysis of RF-spillover-corrected inverse CEST ratio asymmetry for simultaneous
      determination of labile proton ratio and exchange rate.
AB  - Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton
      concentration and exchange rate, thus allowing measurement of dilute CEST agent
      and microenvironmental properties. However, CEST measurement depends not only on
      the CEST agent properties but also on the experimental conditions. Quantitative
      CEST (qCEST) analysis has been proposed to address the limitation of the commonly
      used simplistic CEST-weighted calculation. Recent research has shown that the
      concomitant direct RF saturation (spillover) effect can be corrected using an
      inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is
      feasible with omega plot analysis of the inverse CEST asymmetry calculation.
      Specifically, simulations showed that the numerically derived labile proton ratio
      and exchange rate were in good agreement with input values. In addition, the
      qCEST analysis was confirmed experimentally in a phantom with concurrent
      variation in CEST agent concentration and pH. Also, we demonstrated that the
      derived labile proton ratio increased linearly with creatine concentration (P <
      0.01) while the pH-dependent exchange rate followed a dominantly base-catalyzed
      exchange relationship (P < 0.01). In summary, our study verified that a
      simplified qCEST analysis can simultaneously determine labile proton ratio and
      exchange rate in a relatively complex in vitro CEST system.

PMID- 25615721
TI  - Selenium and exposure to fibrogenic mineral dust: a mini-review.
AB  - Individuals exposed to fibrogenic mineral dust may exhibit an impaired
      antioxidant system and produce high levels of reactive oxygen and nitrogen
      species through immune cells, contributing to the perturbation of immune cell
      function, inflammation, fibrosis and lung cancer. The lung diseases which are
      caused by inhalation of fibrogenic mineral dust, known as pneumoconioses, develop
      progressively and irreversibly over decades. At the moment there is no known
      cure. The trace element selenium has potent antioxidant and anti-inflammatory
      properties mediated mainly through selenoproteins. Research has demonstrated that
      selenium has the ability to protect against cardiovascular diseases; to kill
      cancer cells in vitro and reduce cancer incidence; and to immunomodulate various
      cellular signaling pathways. For these reasons, selenium has been proposed as a
      promising therapeutic agent in oxidative stress associated pathology that in
      theory would be beneficial for the prevention or treatment of pneumoconioses such
      as silicosis, asbestosis, and coal worker's pneumoconiosis. However, studies
      regarding selenium and occupational lung diseases are rare. The purpose of this
      study is to conduct a mini-review regarding the relationship between selenium and
      exposure to fibrogenic mineral dust with emphasis on epidemiological studies. We
      carried out a systematic literature search of English published studies on
      selenium and exposure to fibrogenic mineral dust. We found four epidemiological
      studies. Reviewed studies show that selenium is lower in individuals exposed to
      fibrogenic mineral dust. However, three out of the four reviewed studies could
      not confirm cause-and-effect relationships between low selenium status and
      exposure to fibrogenic mineral dust. This mini-review underscores the need for
      large follow-up and mechanistic studies for selenium to further elucidate its
      therapeutic effects. 

PMID- 25615723
TI  - The effect of sex on humanin levels in healthy adults and patients with
      uncomplicated type 1 diabetes mellitus.
AB  - Diabetes mellitus (DM) is associated with a loss of renal and vascular protection
      in women compared with men, but the responsible mechanisms are unclear. Recent
      experimental work implicated humanin (HN) as a novel cytoprotective hormone in
      DM. Our goal was to measure sex-related differences in HN levels in uncomplicated
      type 1 DM patients (T1D) and healthy controls (HC), as well as the interaction
      between HN, circulating neurohormones, and vascular function. Plasma HN, cGMP and
      aldosterone, blood pressure (BP), glomerular filtration rate, and effective renal
      plasma flow (inulin and para-aminohippurate) were measured in HC (11 men, 10
      women) and T1D (23 men and 18 women) during clamped euglycemia (4-6 mmol.L(-1)).
      Plasma HN levels were generally lower in HC men by comparison with the women, but
      the differences were not statistically significant. In contrast, levels in the
      T1D men were higher compared with the T1D women (p = 0.026) and HC men (p <
      0.0001). In the HC men, but not the women, HN correlated negatively with BP, but
      not with renal function, cGMP, or aldosterone. In the T1D men, HN negatively
      correlated with plasma cGMP. In the T1D women, HN did not correlate with
      neurohormones or vascular function. Future work should determine the role of HN
      in the pathogenesis of sex-related vascular function differences in DM. 

PMID- 25615722
TI  - Temporal structure in associative retrieval.
AB  - Electrophysiological data disclose rich dynamics in patterns of neural activity
      evoked by sensory objects. Retrieving objects from memory reinstates components
      of this activity. In humans, the temporal structure of this retrieved activity
      remains largely unexplored, and here we address this gap using the spatiotemporal
      precision of magnetoencephalography (MEG). In a sensory preconditioning paradigm,
      'indirect' objects were paired with 'direct' objects to form associative links,
      and the latter were then paired with rewards. Using multivariate analysis methods
      we examined the short-time evolution of neural representations of indirect
      objects retrieved during reward-learning about direct objects. We found two
      components of the evoked representation of the indirect stimulus, 200 ms apart.
      The strength of retrieval of one, but not the other, representational component
      correlated with generalization of reward learning from direct to indirect
      stimuli. We suggest the temporal structure within retrieved neural
      representations may be key to their function. 

PMID- 25615724
TI  - Exploration of the (Interrater) Reliability and Latent Factor Structure of the
      Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders
      Identification Test (DUDIT) in a Sample of Dutch Probationers.
AB  - BACKGROUND: The use of brief, reliable, valid, and practical measures of
      substance use is critical for conducting individual (risk and need) assessments
      in probation practice. In this exploratory study, the basic psychometric
      properties of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug
      Use Disorders Identification Test (DUDIT) are evaluated. METHODS: The instruments
      were administered as an oral interview instead of a self-report questionnaire.
      The sample comprised 383 offenders (339 men, 44 women). A subset of 56 offenders
      (49 men, 7 women) participated in the interrater reliability study. Data
      collection took place between September 2011 and November 2012. RESULTS: Overall,
      both instruments have acceptable levels of interrater reliability for total
      scores and acceptable to good interrater reliabilities for most of the individual
      items. Confirmatory factor analyses (CFA) indicated that the a priori one-, two-
      and three-factor solutions for the AUDIT did not fit the observed data very well.
      Principal axis factoring (PAF) supported a two-factor solution for the AUDIT that
      included a level of alcohol consumption/consequences factor (Factor 1) and a
      dependence factor (Factor 2), with both factors explaining substantial variance
      in AUDIT scores. For the DUDIT, CFA and PAF suggest that a one-factor solution is
      the preferred model (accounting for 62.61% of total variance). CONCLUSIONS: The
      Dutch language versions of the AUDIT and the DUDIT are reliable screening
      instruments for use with probationers and both instruments can be reliably
      administered by probation officers in probation practice. However, future
      research on concurrent and predictive validity is warranted.

PMID- 25615725
TI  - A versatile platform of 2-(3,4-dihydroxyphenyl) pyrrolidine grafted graphene for
      preparation of various graphene-derived materials.
AB  - Covalent functionalization has proven an effective solution for graphene to
      realize its revolutionary potential in real applications, whereas the platform
      strategy (a reactive graphene-based material acting as the platform to undergo
      post-reactions for generation of various graphene-derived materials) is an
      attractive option to execute efficiently such a task. This contribution
      demonstrates that 2-(3,4-dihydroxyphenyl) pyrrolidine (DHPP) grafted graphene, G
      OH, is a competent platform. Four typical but not exclusive graphene-derived
      materials have been prepared from G-OH by using the chemical virtue of each DHPP
      unit having three categories totaling six reactive sites. The controlled feature
      of 1,3-dipolar cycloaddition for the synthesis of G-OH ensures that the
      electronic structure and properties of pristine graphene are succeeded largely by
      G-OH and thus its derivatives. A promising alternative to graphene oxide, which
      has been widely used as a platform to prepare the graphene-derived materials but
      suffers from some intrinsic disadvantages, is thus developed. 

PMID- 25615726
TI  - A bio-hybrid tactile sensor incorporating living artificial skin and an impedance
      sensing array.
AB  - The development of a bio-hybrid tactile sensor array that incorporates a skin
      analogue comprised of alginate encapsulated fibroblasts is described. The
      electrical properties are modulated by mechanical stress induced during contact,
      and changes are detected by a ten-channel dual-electrode impedance sensing array.
      By continuously monitoring the impedance of the sensor array at a fixed
      frequency, whilst normal and tangential loads are applied to the skin surface,
      transient mechanotransduction has been observed. The results demonstrate the
      effectiveness and feasibility of the preliminary prototype bio-hybrid tactile
      sensor. 

PMID- 25615727
TI  - A digital sensor simulator of the pushbroom Offner hyperspectral imaging
      spectrometer.
AB  - Sensor simulators can be used in forecasting the imaging quality of a new
      hyperspectral imaging spectrometer, and generating simulated data for the
      development and validation of the data processing algorithms. This paper presents
      a novel digital sensor simulator for the pushbroom Offner hyperspectral imaging
      spectrometer, which is widely used in the hyperspectral remote sensing. Based on
      the imaging process, the sensor simulator consists of a spatial response module,
      a spectral response module, and a radiometric response module. In order to
      enhance the simulation accuracy, spatial interpolation-resampling, which is
      implemented before the spatial degradation, is developed to compromise the
      direction error and the extra aliasing effect. Instead of using the spectral
      response function (SRF), the dispersive imaging characteristics of the Offner
      convex grating optical system is accurately modeled by its configuration
      parameters. The non-uniformity characteristics, such as keystone and smile
      effects, are simulated in the corresponding modules. In this work, the spatial,
      spectral and radiometric calibration processes are simulated to provide the
      parameters of modulation transfer function (MTF), SRF and radiometric calibration
      parameters of the sensor simulator. Some uncertainty factors (the stability, band
      width of the monochromator for the spectral calibration, and the integrating
      sphere uncertainty for the radiometric calibration) are considered in the
      simulation of the calibration process. With the calibration parameters, several
      experiments were designed to validate the spatial, spectral and radiometric
      response of the sensor simulator, respectively. The experiment results indicate
      that the sensor simulator is valid. 

PMID- 25615728
TI  - Automatic frequency controller for power amplifiers used in bio-implanted
      applications: issues and challenges.
AB  - With the development of communication technologies, the use of wireless systems
      in biomedical implanted devices has become very useful. Bio-implantable devices
      are electronic devices which are used for treatment and monitoring brain
      implants, pacemakers, cochlear implants, retinal implants and so on. The
      inductive coupling link is used to transmit power and data between the primary
      and secondary sides of the biomedical implanted system, in which efficient power
      amplifier is very much needed to ensure the best data transmission rates and low
      power losses. However, the efficiency of the implanted devices depends on the
      circuit design, controller, load variation, changes of radio frequency coil's
      mutual displacement and coupling coefficients. This paper provides a
      comprehensive survey on various power amplifier classes and their
      characteristics, efficiency and controller techniques that have been used in bio
      implants. The automatic frequency controller used in biomedical implants such as
      gate drive switching control, closed loop power control, voltage controlled
      oscillator, capacitor control and microcontroller frequency control have been
      explained. Most of these techniques keep the resonance frequency stable in
      transcutaneous power transfer between the external coil and the coil implanted
      inside the body. Detailed information including carrier frequency, power
      efficiency, coils displacement, power consumption, supplied voltage and CMOS chip
      for the controllers techniques are investigated and summarized in the provided
      tables. From the rigorous review, it is observed that the existing automatic
      frequency controller technologies are more or less can capable of performing well
      in the implant devices; however, the systems are still not up to the mark.
      Accordingly, current challenges and problems of the typical automatic frequency
      controller techniques for power amplifiers are illustrated, with a brief
      suggestions and discussion section concerning the progress of implanted device
      research in the future. This review will hopefully lead to increasing efforts
      towards the development of low powered, highly efficient, high data rate and
      reliable automatic frequency controllers for implanted devices. 

PMID- 25615729
TI  - Target tracking and classification from labeled and unlabeled data in wireless
      sensor networks.
AB  - Tracking the locations and identities of moving targets in the surveillance area
      of wireless sensor networks is studied. In order to not rely on high-cost sensors
      that have been used in previous researches, we propose the integrated
      localization and classification based on semi-supervised learning, which uses
      both labeled and unlabeled data obtained from low-cost distributed sensor
      network. In our setting, labeled data are obtained by seismic and PIR sensors
      that contain information about the types of the targets. Unlabeled data are
      generated from the RF signal strength by applying Gaussian process, which
      represents the probability of predicted target locations. Finally, by using
      classified unlabeled data produced by semi-supervised learning, identities and
      locations of multiple targets are estimated. In addition, we consider a case when
      the labeled data are absent, which can happen due to fault or lack of the
      deployed sensor nodes and communication failure. We overcome this situation by
      defining artificial labeled data utilizing characteristics of support vector
      machine, which provides information on the importance of each training data
      point. Experimental results demonstrate the accuracy of the proposed tracking
      algorithm and its robustness to the absence of the labeled data thanks to the
      artificial labeled data. 

PMID- 25615730
TI  - Multisensory system for fruit harvesting robots. Experimental testing in natural
      scenarios and with different kinds of crops.
AB  - The motivation of this research was to explore the feasibility of detecting and
      locating fruits from different kinds of crops in natural scenarios. To this end,
      a unique, modular and easily adaptable multisensory system and a set of
      associated pre-processing algorithms are proposed. The offered multisensory rig
      combines a high resolution colour camera and a multispectral system for the
      detection of fruits, as well as for the discrimination of the different elements
      of the plants, and a Time-Of-Flight (TOF) camera that provides fast acquisition
      of distances enabling the localisation of the targets in the coordinate space. A
      controlled lighting system completes the set-up, increasing its flexibility for
      being used in different working conditions. The pre-processing algorithms
      designed for the proposed multisensory system include a pixel-based
      classification algorithm that labels areas of interest that belong to fruits and
      a registration algorithm that combines the results of the aforementioned
      classification algorithm with the data provided by the TOF camera for the 3D
      reconstruction of the desired regions. Several experimental tests have been
      carried out in outdoors conditions in order to validate the capabilities of the
      proposed system. 

PMID- 25615731
TI  - Collusion-aware privacy-preserving range query in tiered wireless sensor
      networks.
AB  - Wireless sensor networks (WSNs) are indispensable building blocks for the
      Internet of Things (IoT). With the development of WSNs, privacy issues have drawn
      more attention. Existing work on the privacy-preserving range query mainly
      focuses on privacy preservation and integrity verification in two-tiered WSNs in
      the case of compromisedmaster nodes, but neglects the damage of node collusion.
      In this paper, we propose a series of collusion-aware privacy-preserving range
      query protocols in two-tiered WSNs. To the best of our knowledge, this paper is
      the first to consider collusion attacks for a range query in tiered WSNs while
      fulfilling the preservation of privacy and integrity. To preserve the privacy of
      data and queries, we propose a novel encoding scheme to conceal sensitive
      information. To preserve the integrity of the results, we present a verification
      scheme using the correlation among data. In addition, two schemes are further
      presented to improve result accuracy and reduce communication cost. Finally,
      theoretical analysis and experimental results confirm the efficiency, accuracy
      and privacy of our proposals. 

PMID- 25615732
TI  - Pose measurement method and experiments for high-speed rolling targets in a wind
      tunnel.
AB  - High-precision wind tunnel simulation tests play an important role in aircraft
      design and manufacture. In this study, a high-speed pose vision measurement
      method is proposed for high-speed and rolling targets in a supersonic wind
      tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the
      aerodynamic shape of the rolling targets, a high-speed image acquisition method
      based on ultrathin retro-reflection markers is presented. Since markers are small
      sized and some of them may be lost when the target is rolling, a novel markers
      layout with which markers are distributed evenly on the surface is proposed based
      on a spatial coding method to achieve highly accurate pose information.
      Additionally, a pose acquisition is carried out according to the mentioned
      markers layout after removing mismatching points by Case Deletion Diagnostics.
      Finally, experiments on measuring the pose parameters of high-speed targets in
      the laboratory and in a supersonic wind tunnel are conducted to verify the
      feasibility and effectiveness of the proposed method. Experimental results
      indicate that the position measurement precision is less than 0.16 mm, the
      pitching and yaw angle precision less than 0.132 degrees  and the roll angle
      precision 0.712 degrees . 

PMID- 25615733
TI  - Design and experiment of FBG-based icing monitoring on overhead transmission
      lines with an improvement trial for windy weather.
AB  - A scheme for monitoring icing on overhead transmission lines with fiber Bragg
      grating (FBG) strain sensors is designed and evaluated both theoretically and
      experimentally. The influences of temperature and wind are considered. The
      results of field experiments using simulated ice loading on windless days
      indicate that the scheme is capable of monitoring the icing thickness within 0-30
      mm with an accuracy of +/-1 mm, a load cell error of 0.0308v, a repeatability
      error of 0.3328v and a hysteresis error is 0.026%. To improve the measurement
      during windy weather, a correction factor is added to the effective gravity
      acceleration, and the absolute FBG strain is replaced by its statistical average.

PMID- 25615734
TI  - A multi-sensor RSS spatial sensing-based robust stochastic optimization algorithm
      for enhanced wireless tethering.
AB  - The reliability of wireless communication in a network of mobile wireless robot
      nodes depends on the received radio signal strength (RSS). When the robot nodes
      are deployed in hostile environments with ionizing radiations (such as in some
      scientific facilities), there is a possibility that some electronic components
      may fail randomly (due to radiation effects), which causes problems in wireless
      connectivity. The objective of this paper is to maximize robot mission
      capabilities by maximizing the wireless network capacity and to reduce the risk
      of communication failure. Thus, in this paper, we consider a multi-node wireless
      tethering structure called the "server-relay-client" framework that uses
      (multiple) relay nodes in between a server and a client node. We propose a robust
      stochastic optimization (RSO) algorithm using a multi-sensor-based RSS sampling
      method at the relay nodes to efficiently improve and balance the RSS between the
      source and client nodes to improve the network capacity and to provide redundant
      networking abilities. We use pre-processing techniques, such as exponential
      moving averaging and spatial averaging filters on the RSS data for smoothing. We
      apply a receiver spatial diversity concept and employ a position controller on
      the relay node using a stochastic gradient ascent method for self-positioning the
      relay node to achieve the RSS balancing task. The effectiveness of the proposed
      solution is validated by extensive simulations and field experiments in CERN
      facilities. For the field trials, we used a youBot mobile robot platform as the
      relay node, and two stand-alone Raspberry Pi computers as the client and server
      nodes. The algorithm has been proven to be robust to noise in the radio signals
      and to work effectively even under non-line-of-sight conditions. 

PMID- 25615735
TI  - Radio characterization for ISM 2.4 GHz Wireless Sensor Networks for judo
      monitoring applications.
AB  - In this work, the characterization of the radio channel for ISM 2.4GHz Wireless
      Sensor Networks (WSNs) for judo applications is presented. The environments where
      judo activity is held are usually complex indoor scenarios in terms of
      radiopropagation due to their morphology, the presence of humans and the
      electromagnetic interference generated by personal portable devices, wireless
      microphones and other wireless systems used by the media. For the assessment of
      the impact that the topology and the morphology of these environments have on
      electromagnetic propagation, an in-house developed 3D ray-launching software has
      been used in this study. Time domain results as well as estimations of received
      power level have been obtained for the complete volume of a training venue of a
      local judo club's facilities with a contest area with the dimensions specified by
      the International Judo Federation (IJF) for international competitions. The
      obtained simulation results have been compared with measurements, which have been
      carried out deploying ZigBee-compliant XBee Pro modules at presented scenario,
      using approved Judogis (jacket, trousers and belt). The analysis is completed
      with the inclusion of an in-house human body computational model. Such analysis
      has allowed the design and development of an in house application devoted to
      monitor the practice of judo, in order to aid referee activities, training
      routines and to enhance spectator experience. 

PMID- 25615736
TI  - A self-referenced optical intensity sensor network using POFBGs for biomedical
      applications.
AB  - This work bridges the gap between the remote interrogation of multiple optical
      sensors and the advantages of using inherently biocompatible low-cost polymer
      optical fiber (POF)-based photonic sensing. A novel hybrid sensor network
      combining both silica fiber Bragg gratings (FBG) and polymer FBGs (POFBG) is
      analyzed. The topology is compatible with WDM networks so multiple remote sensors
      can be addressed providing high scalability. A central monitoring unit with
      virtual data processing is implemented, which could be remotely located up to
      units of km away. The feasibility of the proposed solution for potential medical
      environments and biomedical applications is shown. 

PMID- 25615737
TI  - A survey of middleware for sensor and network virtualization.
AB  - Wireless Sensor Network (WSN) is leading to a new paradigm of Internet of
      Everything (IoE). WSNs have a wide range of applications but are usually deployed
      in a particular application. However, the future of WSNs lies in the aggregation
      and allocation of resources, serving diverse applications. WSN virtualization by
      the middleware is an emerging concept that enables aggregation of multiple
      independent heterogeneous devices, networks, radios and software platforms; and
      enhancing application development. WSN virtualization, middleware can further be
      categorized into sensor virtualization and network virtualization. Middleware for
      WSN virtualization poses several challenges like efficient decoupling of
      networks, devices and software. In this paper efforts have been put forward to
      bring an overview of the previous and current middleware designs for WSN
      virtualization, the design goals, software architectures, abstracted services,
      testbeds and programming techniques. Furthermore, the paper also presents the
      proposed model, challenges and future opportunities for further research in the
      middleware designs for WSN virtualization. 

PMID- 25615738
TI  - A novel high sensitivity sensor for remote field eddy current non-destructive
      testing based on orthogonal magnetic field.
AB  - Remote field eddy current is an effective non-destructive testing method for
      ferromagnetic tubular structures. In view of conventional sensors' disadvantages
      such as low signal-to-noise ratio and poor sensitivity to axial cracks, a novel
      high sensitivity sensor based on orthogonal magnetic field excitation is
      proposed. Firstly, through a three-dimensional finite element simulation, the
      remote field effect under orthogonal magnetic field excitation is determined, and
      an appropriate configuration which can generate an orthogonal magnetic field for
      a tubular structure is developed. Secondly, optimized selection of key parameters
      such as frequency, exciting currents and shielding modes is analyzed in detail,
      and different types of pick-up coils, including a new self-differential mode pick
      up coil, are designed and analyzed. Lastly, the proposed sensor is verified
      experimentally by various types of defects manufactured on a section of a
      ferromagnetic tube. Experimental results show that the proposed novel sensor can
      largely improve the sensitivity of defect detection, especially for axial crack
      whose depth is less than 40% wall thickness, which are very difficult to detect
      and identify by conventional sensors. Another noteworthy advantage of the
      proposed sensor is that it has almost equal sensitivity to various types of
      defects, when a self-differential mode pick-up coil is adopted. 

PMID- 25615739
TI  - Latitudinal variation in resistance and tolerance to herbivory in the perennial
      herb Lythrum salicaria is related to intensity of herbivory and plant phenology.
AB  - Both the length of the growing season and the intensity of herbivory often vary
      along climatic gradients, which may result in divergent selection on plant
      phenology, and on resistance and tolerance to herbivory. In Sweden, the length of
      the growing season and the number of insect herbivore species feeding on the
      perennial herb Lythrum salicaria decrease from south to north. Previous common
      garden experiments have shown that northern L. salicaria populations develop
      aboveground shoots earlier in the summer and finish growth before southern
      populations do. We tested the hypotheses that resistance and tolerance to damage
      vary with latitude in L. salicaria and are positively related to the intensity of
      herbivory in natural populations. We quantified resistance and tolerance of
      populations sampled along a latitudinal gradient by scoring damage from natural
      herbivores and fitness in a common-garden experiment in the field and by
      documenting oviposition and feeding preference by specialist leaf beetles in a
      glasshouse experiment. Plant resistance decreased with latitude of origin,
      whereas plant tolerance increased. Oviposition and feeding preference in the
      glasshouse and leaf damage in the common-garden experiment were negatively
      related to damage in the source populations. The latitudinal variation in
      resistance was thus consistent with reduced selection from herbivores towards the
      northern range margin of L. salicaria. Variation in tolerance may be related to
      differences in the timing of damage in relation to the seasonal pattern of plant
      growth, as northern genotypes have developed further than southern have when
      herbivores emerge in early summer. 

PMID- 25615740
TI  - New Export Pathway in Plasmodium falciparum-Infected Erythrocytes: Role of the
      Parasite Group II Chaperonin, PfTRiC.
AB  - The export of numerous proteins to the plasma membrane of its host erythrocyte is
      essential for the virulence and survival of the malaria parasite Plasmodium
      falciparum. The Maurer's clefts, membrane structures transposed by the parasite
      in the cytoplasm of its host erythrocyte, play the role of a marshal platform for
      such exported parasite proteins. We identify here the export pathway of three
      resident proteins of the Maurer's clefts membrane: the proteins are exported as
      soluble forms in the red cell cytoplasm to the Maurer's clefts membrane in
      association with the parasite group II chaperonin (PfTRIC), a chaperone complex
      known to bind and address a large spectrum of unfolded proteins to their final
      location. We have also located the domain of interaction with PfTRiC within the
      amino-terminal domain of one of these Maurer's cleft proteins, PfSBP1. Because
      several Maurer's cleft membrane proteins with different export motifs seem to
      follow the same route, we propose a general role for PfTRiC in the trafficking of
      malarial parasite proteins to the host erythrocyte. 

PMID- 25615741
TI  - Potential author misconduct: the education continues.

PMID- 25615742
TI  - Section editor's notebook. Breast density and breast cancer risk-eyes wide open.

PMID- 25615743
TI  - Screening breast ultrasound: past, present, and future.
AB  - OBJECTIVE. This article discusses breast ultrasound for the detection of breast
      cancer in the screening environment, as well as strategies for integrating
      screening breast ultrasound, including automated breast ultrasound. CONCLUSION.
      Breast density is an increasingly pertinent issue in breast cancer diagnosis.
      Breast density results in a decrease in the sensitivity of mammography for cancer
      detection, with a significant increase in the risk of breast cancer. Ultrasound
      detects additional cancers. 

PMID- 25615744
TI  - Journal club: molecular breast imaging at reduced radiation dose for supplemental
      screening in mammographically dense breasts.
AB  - OBJECTIVE. The purpose of this study was to assess the diagnostic performance of
      supplemental screening molecular breast imaging (MBI) in women with
      mammographically dense breasts after system modifications to permit radiation
      dose reduction. SUBJECTS AND METHODS. A total of 1651 asymptomatic women with
      mammographically dense breasts on prior mammography underwent screening
      mammography and adjunct MBI performed with 300-MBq (99m)Tc-sestamibi and a direct
      conversion (cadmium zinc telluride) gamma camera, both interpreted independently.
      The cancer detection rate, sensitivity, specificity, and positive predictive
      value of biopsies performed (PPV3) were determined. RESULTS. In 1585 participants
      with a complete reference standard, 21 were diagnosed with cancer: two detected
      by mammography only, 14 by MBI only, three by both modalities, and two by
      neither. Of 14 participants with cancers detected only by MBI, 11 had invasive
      disease (median size, 0.9 cm; range, 0.5-4.1 cm). Nine of 11 (82%) were node
      negative, and two had bilateral cancers. With the addition of MBI to mammography,
      the overall cancer detection rate (per 1000 screened) increased from 3.2 to 12.0
      (p < 0.001) (supplemental yield 8.8). The invasive cancer detection rate
      increased from 1.9 to 8.8 (p < 0.001) (supplemental yield 6.9), a relative
      increase of 363%, while the change in DCIS detection was not statistically
      significant (from 1.3 to 3.2, p =0.250). For mammography alone, sensitivity was
      24%; specificity, 89%; and PPV3, 25%. For the combination, sensitivity was 91% (p
      < 0.001); specificity, 83% (p < 0.001); and PPV3, 28% (p = 0.70). The recall rate
      increased from 11.0% with mammography alone to 17.6% (p < 0.001) for the
      combination; the biopsy rate increased from 1.3% for mammography alone to 4.2% (p
      < 0.001). CONCLUSION. When added to screening mammography, MBI performed using a
      radiopharmaceutical activity acceptable for screening (effective dose 2.4 mSv)
      yielded a supplemental cancer detection rate of 8.8 per 1000 women with
      mammographically dense breasts. 

PMID- 25615745
TI  - Alternative screening for women with dense breasts: breast-specific gamma imaging
      (molecular breast imaging).
AB  - OBJECTIVE. Given mammography's limitations in evaluating dense breasts,
      examination with breast-specific gamma imaging (BSGI)-also called molecular
      breast imaging (MBI)-has been proposed. We review the literature pertinent to the
      performance of BSGI in patients with dense breasts. CONCLUSION. Many studies have
      reported the sensitivity of BSGI in finding cancers even in dense breasts.
      However, BSGI has not yet been validated as an effective screening tool in large
      prospective studies. In addition, whole-body dose remains a significant concern. 

PMID- 25615746
TI  - Breast density legislation: mandatory disclosure to patients, alternative
      screening, billing, reimbursement.
AB  - OBJECTIVE. The purpose of this article is describe the origins and provisions of
      breast density legislation and to evaluate these mandates with regard to the
      balance between the potential benefit of supplementary screening and the
      substantial risk of false-positive findings and the adjunctive tests they
      necessitate. CONCLUSION. Many states have passed breast density notification
      legislation, and federal legislation is pending. These mandates present a number
      of challenges for patients and physicians. There is no consensus regarding the
      need for supplementary testing solely because a woman has dense breasts. The
      failure of density legislation to require insurance coverage in many states
      further complicates implementation of the mandates. 

PMID- 25615747
TI  - Screening for dense breasts: digital breast tomosynthesis.
AB  - OBJECTIVE. Digital breast tomosynthesis (DBT) is a recent imaging technology that
      was developed to address the limitations of conventional 2D mammography. The
      limitations of standard mammography are well known and include reduced
      sensitivity in dense breasts. Clinical research studies of DBT and the
      implementation of DBT have revealed that DBT has potential benefits for
      evaluating patients with dense breasts. This article will discuss the benefits
      and limitations of DBT as a screening alternative for women with dense breasts.
      CONCLUSION. Studies to date have revealed that the use of DBT reduces recall
      rates and increases cancer detection rates. This has been demonstrated with the
      use of DBT for both screening and diagnostic purposes, as well as with imaging
      dense breasts. DBT has the ability to reduce breast tissue overlap, thus
      potentially revealing lesions that would otherwise have been missed. The
      limitations of DBT include longer interpretation times, higher costs, and
      increased radiation dose. These limitations present challenges that radiologists
      must consider before DBT implementation. 

PMID- 25615748
TI  - Training and standards for performance, interpretation, and structured reporting
      for supplemental breast cancer screening.
AB  - OBJECTIVE. To compensate for the reduction of mammography's sensitivity in women
      with dense breasts, supplemental screening can increase the cancer detection
      rate. The modalities suggested are MRI, which is the most sensitive and is
      indicated for women with the highest risk of breast cancer, and ultrasound, which
      is suggested for dense-breasted average-risk women. CONCLUSION. For decades,
      ultrasound has been a focused examination. Extending a handheld ultrasound
      examination to depict the entire breast requires formal didactic training and
      hands-on scanning to learn suitable, efficient methods. Automated options also
      require intensive training in performance and interpretation. 

PMID- 25615749
TI  - Emerging role of cardiovascular CT and MRI in the evaluation of stroke.
AB  - OBJECTIVE. The purposes of this article are to explore the potential for use of
      CT angiography and MRI and to highlight data suggestive of their usefulness in
      specific cardiovascular abnormalities. CONCLUSION. The evaluation of stroke
      requires comprehensive assessment of potential stroke mechanisms, including
      cardiac sources. Despite an exhaustive search for secondary causes, the precise
      cause of many strokes remains unknown (cryptogenic). It is well recognized,
      however, that some of these potential causes occur as a result of embolism from
      the heart or great vessels. Thus, echocardiography, in particular transesophageal
      echocardiography, is instrumental in a careful assessment of cardiac causes in
      selected individuals. Unfortunately, transesophageal echocardiography is
      invasive, and some patients may have relative or absolute contraindications.
      Cardiovascular CT angiography and MRI have growing potential compared with
      conventional cardiovascular echography. 

PMID- 25615750
TI  - Evaluation of image registration in subtracted 3D dynamic contrast-enhanced MRI
      of treated hepatocellular carcinoma.
AB  - OBJECTIVE. The objective of our study was to quantify hepatic displacement
      between breath-holds in multiphasic contrast-enhanced MRI and assess the value of
      a 3D registration algorithm for displacement correction on subtracted images.
      MATERIALS AND METHODS. For this retrospective analysis, we evaluated MR images of
      25 cirrhotic patients with treated hepatocellular carcinoma (HCC) and at least
      one coexisting small hepatic cyst that was hypointense on T1-weighted imaging.
      With the use of an automated 3D deformable registration algorithm, registered
      base and subtraction images were created using portal venous phase images as the
      baseline images. The relative displacement of the cysts over the dynamic phases
      was used to estimate hepatic displacement before and after registration. The
      width of the subtraction band artifact, HCC lesion conspicuity, and overall
      subtraction artifact level (i.e., image quality of the entire volume) of the
      subtraction images were evaluated before and after registration on a 5-point
      scale (1 = nondiagnostic, 5 = excellent image quality) by two blinded
      radiologists. Hepatic displacement and subtraction band artifact results were
      analyzed using the paired Student t test, and the results for HCC lesion
      conspicuity and image quality of the volume results were analyzed using the
      Wilcoxon signed rank test. Interobserver agreement was assessed using kappa
      statistics. RESULTS. The average total cyst displacement on unenhanced, arterial,
      and delayed phase images was significantly reduced by registration from 4.0, 3.2,
      and 4.6 mm, respectively, on pre-registered images to 2.4, 1.6, and 1.3 mm on
      postregistered images (p < 0.01). The mean HCC lesion conspicuity grade improved
      from 3.4 before registration to 4.4 after registration (p < 0.01), and the mean
      grade for image quality of the volume improved from 3.3 before registration to
      4.6 after registration (p < 0.01). The average width of the subtraction band
      artifact decreased from 5.3 mm before registration to 2.4 mm after registration,
      from 6.1 mm before registration to 2.6 mm after registration, and from 5.2 mm
      before registration to 2.8 mm after registration for the arterial, portal venous,
      and delayed phase subtractions, respectively (p < 0.01). CONCLUSION. Automated
      registration of the liver in multiphasic MRI examinations reduced interphasic
      hepatic displacement, improved the conspicuity of the treated HCC lesion, and
      improved the overall subtraction image quality.

PMID- 25615751
TI  - Quantification of hepatic steatosis with a multistep adaptive fitting MRI
      approach: prospective validation against MR spectroscopy.
AB  - OBJECTIVE. The purpose of this study is to prospectively compare hybrid and
      complex chemical shift-based MRI fat quantification methods against MR
      spectroscopy (MRS) for the measurement of hepatic steatosis. SUBJECTS AND
      METHODS. Forty-two subjects (18 men and 24 women; mean +/- SD age, 52.8 +/- 14
      years) were prospectively enrolled and imaged at 3 T with a chemical shift-based
      MRI sequence and a single-voxel MRS sequence, each in one breath-hold. Proton
      density fat fraction and rate constant (R2*) using both single- and dual-R2*
      hybrid fitting methods, as well as proton density fat fraction and R2* maps using
      a complex fitting method, were generated. A single radiologist colocalized
      volumes of interest on the proton density fat fraction and R2* maps according to
      the spectroscopy measurement voxel. Agreement among the three MRI methods and the
      MRS proton density fat fraction values was assessed using linear regression,
      intraclass correlation coefficient (ICC), and Bland-Altman analysis. RESULTS.
      Correlation between the MRI and MRS measures of proton density fat fraction was
      excellent. Linear regression coefficients ranged from 0.98 to 1.01, and
      intercepts ranged from -1.12% to 0.49%. Agreement measured by ICC was also
      excellent (0.99 for all three methods). Bland-Altman analysis showed excellent
      agreement, with mean differences of -1.0% to 0.6% (SD, 1.3-1.6%). CONCLUSION. The
      described MRI-based liver proton density fat fraction measures are clinically
      feasible and accurate. The validation of proton density fat fraction
      quantification methods is an important step toward wide availability and
      acceptance of the MRI-based measurement of proton density fat fraction as an
      accurate and generalizable biomarker. 

PMID- 25615752
TI  - Usefulness of a metal artifact reduction algorithm for orthopedic implants in
      abdominal CT: phantom and clinical study results.
AB  - OBJECTIVE. The purpose of this study was to evaluate the usefulness of a metal
      artifact reduction (MAR) algorithm for orthopedic prostheses in phantom and
      clinical CT. MATERIALS AND METHODS. An agar phantom with two sets of spinal
      screws was scanned at various tube voltage (80-140 kVp) and tube current-time (34
      1032 mAs) settings. The orthopedic MAR algorithm was combined with filtered back
      projection (FBP) or iterative reconstruction. The mean SDs in three ROIs were
      compared among four datasets (FBP, iterative reconstruction, FBP with orthopedic
      MAR, and iterative reconstruction with orthopedic MAR). For the clinical study,
      the mean SDs of three ROIs and 4-point scaled image quality in 52 patients with
      metallic orthopedic prostheses were compared between CT images acquired with and
      without orthopedic MAR. The presence and type of image quality improvement with
      orthopedic MAR and the presence of orthopedic MAR-related new artifacts were also
      analyzed. RESULTS. In the phantom study, the mean SD with orthopedic MAR was
      significantly lower than that without orthopedic MAR regardless of dose settings
      and reconstruction algorithms (FBP versus iterative reconstruction). The mean SD
      near the metallic prosthesis in 52 patients was significantly lower on CT images
      with orthopedic MAR (28.04 HU) than those without it (49.21 HU). Image quality
      regarding metallic artifact was significantly improved with orthopedic MAR
      (rating of 2.60 versus 1.04). Notable reduction of metallic artifacts and better
      depiction of abdominal organs were observed in 45 patients. Diagnostic benefit
      was achieved in six patients, but orthopedic MAR-related new artifacts were seen
      in 30 patients. CONCLUSION. Use of the orthopedic MAR algorithm significantly
      reduces metal artifacts in CT of both phantoms and patients and has potential for
      improving diagnostic performance in patients with severe metallic artifacts. 

PMID- 25615753
TI  - Yield of urinary tract cancer diagnosis with repeat CT urography in patients with
      hematuria.
AB  - OBJECTIVE. The purpose of this study was to evaluate the yield of repeat CT
      urography (CTU) in detecting urinary tract malignancies in patients with
      hematuria. MATERIALS AND METHODS. A review of 5525 patients who underwent CTU
      between 2000 and 2011 revealed 751 (13.6%) patients who underwent repeat CTU. We
      excluded 127 patients with more than 3 years between examinations, 409 with
      nonhematuria indications, and 13 with less than 1 year of follow-up from a
      negative repeat examination. An additional 54 patients with malignancy diagnosed
      on the initial evaluation were excluded, leaving 148 patients in the study cohort
      (77 men and 71 women; mean age, 57 years). Patients were categorized on the basis
      of the presence or absence of findings suspicious for malignancy on initial CTU
      reports. Repeat CTU reports were correlated with cystoscopy, pathology, and
      clinical follow-up to determine the incidence of malignancy. Examinations
      negative for malignancy were confirmed with at least 1 year of clinical follow
      up. CTU examinations of patients diagnosed with malignancy on repeat examination
      were reviewed by two radiologists in consensus. RESULTS. Initial CTU showed no
      findings suspicious for malignancy in 103 (70%) of 148 patients; of these, none
      had malignancy identified on repeat CTU. Among 45 (30%) patients with suspicious
      initial CTU findings, four malignancies were identified on repeat CTU (8.9%).
      Three were incidental to the initial suspicious finding; in retrospect, two were
      present on the initial CTU examination. CONCLUSION. In patients with hematuria,
      repeat CTU within 3 years is unlikely to show a urinary tract malignancy. These
      results support currently published guidelines. 

PMID- 25615754
TI  - Acoustic radiation force impulse imaging for evaluation of renal parenchyma
      elasticity in diabetic nephropathy.
AB  - OBJECTIVE. The goal of this study is to evaluate the changes in the elasticity of
      the renal parenchyma in diabetic nephropathy using acoustic radiation force
      impulse imaging. SUBJECTS AND METHODS. The study included 281 healthy volunteers
      and 114 patients with diabetic nephropathy. In healthy volunteers, the kidney
      elasticity was assessed quantitatively by measuring the shear-wave velocity using
      acoustic radiation force impulse imaging based on age, body mass index, and sex.
      The changes in the renal elasticity were compared between the different stages of
      diabetic nephropathy and the healthy control group. RESULTS. In healthy
      volunteers, there was a statistically significant correlation between the shear
      wave velocity values and age and sex. The shear-wave velocity values for the
      kidneys were 2.87, 3.14, 2.95, 2.68, and 2.55 m/s in patients with stage 1, 2, 3,
      4, and 5 diabetic nephropathy, respectively, compared with 2.35 m/s for healthy
      control subjects. Acoustic radiation force impulse imaging was able to
      distinguish between the different diabetic nephropathy stages (except for stage
      5) in the kidneys. The threshold value for predicting diabetic nephropathy was
      2.43 m/s (sensitivity, 84.1%; specificity, 67.3%; positive predictive value,
      93.1%; negative predictive value 50.8%; accuracy, 72.1%; positive likelihood
      ratio, 2.5; and negative likelihood ratio, 0.23). CONCLUSION. Acoustic radiation
      force impulse imaging could be used for the evaluation of the renal elasticity
      changes that are due to secondary structural and functional changes in diabetic
      nephropathy. 

PMID- 25615755
TI  - Multiparametric 3-T MRI for differentiating low-versus high-grade and category T1
      versus T2 bladder urothelial carcinoma.
AB  - OBJECTIVE. The purpose of this study was to determine an optimal multiparametric
      MRI protocol for characterizing tumors of low versus high grade and
      differentiating tumors as T1 versus T2 for preoperative staging of bladder
      urothelial carcinoma. SUBJECTS AND METHODS. Thirty-nine patients underwent MRI
      within 1 week before surgery. Three image sets-T2-weighted plus diffusion
      weighted MRI (DWI), T2-weighted plus dynamic contrast-enhanced MRI (DCE-MRI), and
      T2-weighted plus DCEMRI plus DWI-were independently interpreted by two readers at
      2-week intervals. ROC curves were plotted for both readers to compare the
      diagnostic efficacy of the three sets for detrusor muscle invasion for each
      reader, and the areas under the ROC curve were compared by use of the Bonferroni
      test. The apparent diffusion coefficient (ADC) values were correlated with
      histopathologic grade. RESULTS. A total of 49 category T1 and T2 lesions were
      analyzed. The average ADC of 11 low-grade tumors (1.141 +/- 0.164 * 10(-3)
      mm(2)/s) was significantly (p < 0.05) higher than that of 20 high-grade malignant
      tumors (0.766 +/- 0.091 * 10(-3) mm(2)/s). Neither reader considered T1 tumors as
      probably having muscle invasion (category T2) in the T2-weighted plus DWI image
      sets or the T2-weighted plus DWI plus DCE-MRI image sets. Using the T2-weighted
      plus DCE-MRI sets, the two readers overstaged 13 and 15 of 36 tumors by
      misdiagnosing category T1 as T2. With the cutoff ADC value of 0.899 * 10-3
      mm(2)/s, the sensitivity and specificity for differentiating high- and low-grade
      bladder urothelial carcinoma were 100% and 95%. CONCLUSION. Multiparametric MRI
      with T2-weighted plus DWI plus DCE technique is the optimal protocol for
      preoperative staging of organ-confined bladder urothelial carcinoma. The ADC of
      low-grade tumors is significantly higher than that of high-grade tumors with 100%
      sensitivity and 95% specificity at a cutoff ADC value of 0.899 mm(2)/s. 

PMID- 25615756
TI  - Radiation exposure from CT-guided ablation of renal masses: effects on life
      expectancy.
AB  - OBJECTIVE. The purpose of this article is to project the effects of radiation
      exposure on life expectancy (LE) in patients who opt for CT-guided radiofrequency
      ablation (RFA) instead of surgery for renal cell carcinoma (RCC). MATERIALS AND
      METHODS. We developed a decision-analytic Markov model to compare LE losses
      attributable to radiation exposure in hypothetical 65-year-old patients who
      undergo CT-guided RFA versus surgery for small (<= 4 cm) RCC. We incorporated
      mortality risks from RCC, radiation-induced cancers (for procedural and follow-up
      CT scans), and all other causes; institutional data informed the RFA procedural
      effective dose. Radiation-induced cancer risks were generated using an organ
      specific approach. Effects of varying model parameters and of dose-reduction
      strategies were evaluated in sensitivity analysis. RESULTS. Cumulative RFA
      exposures (up to 305.2 mSv for one session plus surveillance) exceeded those from
      surgery (up to 87.2 mSv). In 65-year-old men, excess LE loss from radiation
      induced cancers, comparing RFA to surgery, was 11.7 days (14.6 days for RFA vs
      2.9 days for surgery). Results varied with sex and age; this difference increased
      to 14.6 days in 65-year-old women and to 21.5 days in 55-year-old men. Dose
      reduction strategies that addressed follow-up rather than procedural exposure had
      a greater impact. In 65-year-old men, this difference decreased to 3.8 days if
      post-RFA follow-up scans were restricted to a single phase; even elimination of
      RFA procedural exposure could not achieve equivalent benefits. CONCLUSION. CT
      guided RFA remains a safe alternative to surgery, but with decreasing age, the
      higher burden of radiation exposure merits explicit consideration. Dose-reduction
      strategies that target follow-up rather than procedural exposure will have a
      greater impact. 

PMID- 25615757
TI  - Lack of security of networked medical equipment in radiology.
AB  - OBJECTIVE. There are few articles in the literature describing the security and
      safety aspects of networked medical equipment in radiology departments. Most
      radiologists are unaware of the security issues. We review the security of the
      networked medical equipment of a typical radiology department. MATERIALS AND
      METHODS. All networked medical equipment in a radiology department was scanned
      for vulnerabilities with a port scanner and a network vulnerability scanner, and
      the vulnerabilities were classified using the Common Vulnerability Scoring
      System. A network sniffer was used to capture and analyze traffic on the
      radiology network for exposure of confidential patient data. We reviewed the use
      of antivirus software and firewalls on the networked medical equipment. USB ports
      and CD and DVD drives in the networked medical equipment were tested to see
      whether they allowed unauthorized access. Implementation of the virtual private
      network (VPN) that vendors use to access the radiology network was reviewed.
      RESULTS. Most of the networked medical equipment in our radiology department used
      vulnerable software with open ports and services. Of the 144 items scanned, 64
      (44%) had at least one critical vulnerability, and 119 (83%) had at least one
      high-risk vulnerability. Most equipment did not encrypt traffic and allowed
      capture of confidential patient data. Of the 144 items scanned, two (1%) used
      antivirus software and three (2%) had a firewall enabled. The USB ports were not
      secure on 49 of the 58 (84%) items with USB ports, and the CD or DVD drive was
      not secure on 17 of the 31 (55%) items with a CD or DVD drive. One of three
      vendors had an insecure implementation of VPN access. CONCLUSION. Radiologists
      and the medical industry need to urgently review and rectify the security issues
      in existing networked medical equipment. We hope that the results of our study
      and this article also raise awareness among radiologists about the security
      issues of networked medical equipment. 

PMID- 25615758
TI  - Imaging of adult flatfoot: correlation of radiographic measurements with MRI.
AB  - OBJECTIVE. The purpose of this study is to determine whether radiographic foot
      measurements can predict injury of the posterior tibial tendon (PTT) and the
      supporting structures of the medial longitudinal arch as diagnosed on MRI.
      MATERIALS AND METHODS. After institutional review board approval, 100 consecutive
      patients with radiographic and MRI examinations performed within a 2-month period
      were enrolled. Thirty-one patients had PTT dysfunction clinically, and 69
      patients had other causes of ankle pain. Talonavicular uncoverage angle,
      incongruency angle, calcaneal pitch angle, Meary angle, cuneiform-to-fifth
      metatarsal height, and talar tilt were calculated on standing foot or ankle
      radiographs. MRI was used to assess for abnormalities of the PTT (tenosynovitis,
      tendinosis, and tear) and supporting structures of the medial longitudinal arch
      (spring ligament, deltoid ligament, and sinus tarsi). Statistical analysis was
      performed using the chi-square and Fisher exact tests for categoric variables;
      the Student t test was used for continuous variables. RESULTS. There was a
      statistically significant association of PTT tear with abnormal talonavicular
      uncoverage angle, calcaneal pitch angle, Meary angle, and cuneiform-to-fifth
      metatarsal height. PTT tendinosis and isolated tenosynovitis had a poor
      association with most radiologic measurements. If both calcaneal pitch and Meary
      angles were normal, no PTT tear was present. An abnormal calcaneal pitch angle
      had the best association with injury to the supporting medial longitudinal arch
      structures. CONCLUSION. Radiographic measurements, especially calcaneal pitch and
      Meary angles, can be useful in detecting PTT tears. Calcaneal pitch angle
      provides the best assessment of injury to the supporting structures of the medial
      longitudinal arch.

PMID- 25615759
TI  - Delaminated tears of the rotator cuff: prevalence, characteristics, and
      diagnostic accuracy using indirect MR arthrography.
AB  - OBJECTIVE. The purpose of this study was to evaluate the prevalence, radiologic
      characteristics, and accuracy of diagnosing delaminated tears at the
      supraspinatus tendon-infraspinatus tendon (SST-IST) on indirect MR arthrography.
      MATERIALS AND METHODS. Of 531 consecutive shoulders that underwent indirect MR
      arthrography, 231 shoulders with tears at the SST-IST were included. On the MR
      images, delaminated tears at the SST-IST, defined as intratendinous horizontal
      splitting between the articular and bursal layers of the SST-IST with or without
      different degrees of retraction between the two layers, were identified and
      classified into six types. Other radiologic findings of the SST-IST, such as the
      presence of intramuscular cysts, were evaluated. We used video records of 127
      arthroscopic surgeries to determine the diagnostic accuracy of indirect MRI for
      the detection of the delaminated tears at the SST-IST. RESULTS. On MRI, 56%
      (129/231) of shoulders with SST-IST tears had delaminated tears. Articular
      delaminated full-thickness tears (n = 58) and articular-delaminated partial
      thickness tears (n = 64) were the most common types. Approximately 82% (36/44) of
      articular-delaminated full-thickness tears occurring at the SST were combined
      with articular-delaminated partial-thickness tears at the IST. SST-IST footprint
      tears and intramuscular cysts were significantly more common in the shoulders
      with delaminated tears. The sensitivity and specificity of indirect MR
      arthrography for detection of delaminated tears were 92% and 94%, respectively.
      CONCLUSION. On indirect MR arthrography, approximately half of the shoulders with
      SST-IST tears had delaminated tears. The diagnostic accuracy of indirect MR
      arthrography for detection of delaminated tears was high. 

PMID- 25615760
TI  - The anterolateral ligament of the knee: MRI appearance, association with the
      Segond fracture, and historical perspective.
AB  - OBJECTIVE. A recent publication has drawn attention to the anterolateral
      ligament, a structure of the knee with which most radiologists are unfamiliar. We
      evaluate this structure on MRI; clarify its origin, insertion, meniscal
      relationship, and morphologic appearance; and identify its relationship with the
      Segond fracture. MATERIALS AND METHODS. A total of 53 routine knee MRI studies
      interpreted as normal were reviewed to characterize the anterolateral ligament. A
      further 20 knee MRI studies with a Segond fracture were assessed to determine a
      relationship between the fracture and the anterolateral ligament. RESULTS. In all
      53 cases, a structure was present along the lateral knee connecting the distal
      femur to the proximal tibia, with meniscofemoral and meniscotibial components.
      This structure was somewhat ill defined and sheetlike, inseparable from the
      adjacent fibular collateral ligament proximally and iliotibial band distally.
      Aside from one case limited by anatomic distortion, all cases with a Segond
      fracture exhibited attachment of this structure to the fracture fragment (19/20
      cases). CONCLUSION. An ill-defined sheetlike structure along the lateral knee
      exists attaching the distal femur, body of lateral meniscus, and proximal tibia.
      This structure has been referenced in the literature dating back to Paul Segond's
      original description of the Segond fracture in 1879. The structure is
      identifiable on MRI and appears to be attached to the Segond fracture fragment.
      For the radiologist, it may be best to forgo an attempt to separate this
      structure into discrete divisions, such as the anterolateral ligament, because
      these individual components are inseparable on routine MRI.

PMID- 25615761
TI  - Myxoid soft-tissue neoplasms: comprehensive update of the taxonomy and MRI
      features.
AB  - OBJECTIVE. The purpose of this article is to review the classification, clinical
      presentation, and histopathologic and MRI features of myxoid soft-tissue
      neoplasms. CONCLUSION. MRI is the modality of choice for characterization of
      myxoid soft-tissue tumors. A combination of imaging features (including certain
      characteristic signs), clinical features, and patient demographics can help the
      radiologist in coming to a specific diagnosis or in narrowing down the
      differential diagnoses. 

PMID- 25615762
TI  - Surgical management of retrorectal lesions: what the radiologist needs to know.
AB  - OBJECTIVE. The purpose of this article is to highlight the most salient imaging
      features of retrorectal masses with regard to surgical planning, preoperative
      biopsy, and identification of nonneoplastic mimickers of malignancy. CONCLUSION.
      Retrorectal tumors are associated with high morbidity. CT and MRI aid in
      preoperative planning because surgical resection is the treatment of choice for
      both benign and malignant entities. Radiologists need to understand the operative
      techniques currently used for retrorectal tumors because the first attempt at
      excision is the best chance for complete resection and optimal outcome. 

PMID- 25615763
TI  - Ultrasound elastography using carotid artery pulsation in the differential
      diagnosis of sonographically indeterminate thyroid nodules.
AB  - OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance
      of gray-scale ultrasound and a new method of thyroid ultrasound elastography
      using carotid artery pulsation in the differential diagnosis of sonographically
      indeterminate thyroid nodules. MATERIALS AND METHODS. A total of 102 thyroid
      nodules with indeterminate gray-scale ultrasound features from 102 patients (20
      males and 82 females; age range, 16-74 years; mean age, 51 years) were included.
      The gray-scale ultrasound images of each nodule were reviewed and assigned a
      score from 1 (low) to 5 (high) according to the possibility of malignancy.
      Ultrasound elastography was performed using carotid pulsation as the compression
      source. The elasticity contrast index (ECI), which quantifies local strain
      contrast within a nodule, was automatically calculated. The radiologist
      reassessed the scores after concurrently reviewing gray-scale ultrasound and
      elastography. ROC curve analysis was used to evaluate the diagnostic performances
      of each dataset and to compare the AUC (Az) values of gray-scale ultrasound score
      alone, ECI alone, and a combined assessment. RESULTS. Significantly more
      malignant thyroid nodules were hypoechoic than benign nodules (p = 0.014). The
      ECI was significantly higher in malignant nodules than in benign thyroid nodules.
      The Az values of each dataset were 0.755 (95% CI, 0.660-0.835) for gray-scale
      ultrasound score, 0.835 (0.748-0.901) for ECI, and 0.853 (0.769-0.915) for a
      combined assessment. The Az value for a combined assessment of the gray-scale
      ultrasound score and the ECI was significantly higher than that for the gray
      scale ultrasound score alone (p = 0.022). CONCLUSION. Combined assessment with
      gray-scale ultrasound and elastography using carotid artery pulsation is helpful
      for characterizing sonographically indeterminate thyroid nodules as benign or
      malignant. 

PMID- 25615765
TI  - Multimodality thoracic imaging of juvenile systemic sclerosis: emphasis on
      clinical correlation and high-resolution CT of pulmonary fibrosis.
AB  - OBJECTIVE. Juvenile systemic sclerosis is a rare multisystem autoimmune disorder
      characterized by vasculopathy and multiorgan fibrosis. Cardiopulmonary
      complications are the leading cause of morbidity and mortality. Although
      pulmonary fibrosis is the complication that is most common and well described,
      cardiovascular and esophageal involvement may also be observed. In this article,
      common thoracic findings in juvenile systemic sclerosis will be discussed. We
      will focus on chest CT, including CT findings of pulmonary fibrosis and
      associated grading methods, as well as cardiac MRI and esophageal imaging.
      CONCLUSION. Radiologists play a pivotal role in the initial diagnosis and follow
      up evaluation of pediatric patients with systemic sclerosis. Treatment decisions
      and prognostic assessment are directly related to imaging findings along with
      clinical evaluation. 

PMID- 25615764
TI  - Two-time-point FDG PET/CT: liver SULmean repeatability.
AB  - OBJECTIVE. The purpose of this study was to evaluate the repeatability of liver
      mean standardized uptake value normalized to lean body mass (SULmean) in the same
      patients at different time points within the right lobe of the liver at (18)F-FDG
      PET/CT, in a clinical setting. MATERIALS AND METHODS. Two PET/CT studies
      performed on two different dates from each of 130 patients who had normal livers
      according to structural imaging were included in this reader study. The mean (+/-
      SD) length of time between the studies was 235 +/- 192 days. SULmean was measured
      with a 30-mm diameter spherical volume of interest (VOI) placed within the right
      lobe of the liver (above, below, and at the level of the main portal vein) by two
      expert readers. ANOVA, intraclass correlation coefficient (ICC), and Bland-Altman
      analysis were performed. RESULTS. The ICC for the first and second set of studies
      varied between 0.487 and 0.535 for reader 1 and between 0.472 and 0.545 for
      reader 2. The mean percentage variation for SULmean between the two time scans
      for the VOIs placed above, below, and at the level of the main portal vein were
      3.55% +/- 23.19%, 4.65% +/- 23.87%, and 4.30% +/- 23.03%, respectively, for
      reader 1 and 4.49% +/- 23.23%, 4.33% +/- 23.74%, and 4.48% +/- 23.01%,
      respectively, for reader 2. Using 95% CI, the reference range for intrapatient
      variations between the studies in liver SULmean was -0.5 to 0.60. CONCLUSION.
      There is only fair repeatability of liver SULmean measured between two time
      points in the same patient in a clinical setting. Scan-to-scan intrapatient
      variation in absolute liver SULmean was -0.5 to 0.60. 

PMID- 25615766
TI  - Evaluation of contrast injection site effectiveness: thoracic CT angiography in
      children with hand injection of IV contrast material.
AB  - OBJECTIVE. The purpose of this study was to evaluate the effectiveness of various
      contrast injection sites when performing thoracic CT angiography (CTA) using hand
      injection of IV contrast material in infants and young children with a small IV
      catheter. MATERIALS AND METHODS. We used our hospital information system to
      retrospectively identify consecutive pediatric patients who underwent thoracic
      CTA with hand injection of contrast material from August 2012 to July 2013. The
      study indication for thoracic CTA was to evaluate the thoracic systemic arterial
      vasculature and pulmonary venous vasculature. Both qualitative and quantitative
      evaluation of thoracic CTA image quality was performed by two reviewers
      independently. Qualitative evaluation of thoracic CTA image quality was performed
      by visual assessment of the degree of contrast enhancement in the ROI on a 4
      point scale. Quantitative evaluation was performed by measuring attenuation
      obtained with the ROI placed within the aorta at two locations (the level of the
      aortic arch and at the level of the carina) to evaluate the thoracic systemic
      arterial vasculature. For evaluation of the pulmonary venous system, attenuation
      measurements were obtained at the center of the left atrium. Six individual
      injection sites were identified: head, jugular vein, arm vein, hand vein, leg
      vein, and foot vein. Injection sites were categorized into three regional groups:
      head-neck region (head vein and jugular veins), upper extremity region (arm and
      hand veins), and lower extremity region (leg and foot veins). Comparisons of
      attenuation values between individual and regionally grouped contrast injection
      sites were determined using the F-test in ANOVA. RESULTS. The study cohort
      included 50 pediatric patients (29 boys and 21 girls; mean age, 8 months +/- 1
      year; range, 1 week to 5 years) who underwent a total of 50 thoracic CTA studies
      for evaluating the thoracic systemic arterial vasculature (n = 38; 76%) or
      pulmonary venous vasculature (n = 12; 34%). All 50 thoracic CTA studies were of
      diagnostic quality on the basis of qualitative evaluation (all >= 3). For
      quantitative evaluation with the threshold for a diagnostic thoracic CTA study
      defined as attenuation greater than 150 HU in the ROI, all 50 thoracic CTA
      studies were technically successful (aortic arch, 380 +/- 150 HU; descending
      thoracic aorta at the level of the carina, 392 +/- 155 HU; and left atrium, 352
      +/- 90 HU). There were no significant differences in mean attenuation between
      individual injection sites (p > 0.20 for each comparison) or different regional
      groups (p > 0.50 for each comparison). CONCLUSION. Diagnostic quality thoracic
      CTA can be achieved with hand injection of IV contrast material in infants and
      young children with a small IV catheter, independent of the IV access site. 

PMID- 25615767
TI  - Imaging findings of pediatric rheumatologic emergencies.
AB  - OBJECTIVE. Pediatric rheumatologic diseases can present with a wide spectrum of
      clinical features, affecting any organ in the body and causing significant
      morbidity and mortality. The aim of this review is to emphasize the diagnostic
      imaging findings of pediatric rheumatologic emergencies and to discuss their
      pertinent complications. CONCLUSION. Because of their multiorgan and multisystem
      involvement, pediatric rheumatologic diseases comprise a wide spectrum of
      differential diagnosis. Although the diagnosis may generally not be time
      critical, for a few conditions, prompt recognition is crucial to preserving organ
      function or the patient's life [ 1 ]. 

PMID- 25615768
TI  - Survival outcomes in patients with advanced hepatocellular carcinoma treated with
      drug-eluting bead chemoembolization.
AB  - OBJECTIVE. The purpose of this study was to determine the overall survival rates
      in patients with advanced hepatocellular carcinoma (HCC) who undergo treatment
      with drug-eluting bead (DEB) therapy. MATERIALS AND METHODS. A retrospective
      review of the clinical HCC database of a single institution was undertaken for
      patients treated between September 2008 and December 2011. Demographic
      information, laboratory and imaging findings, procedural details, and outcomes
      after treatment were obtained. The primary outcome was overall survival, which
      was stratified by Barcelona Clinic Liver Cancer (BCLC) stage, Child-Pugh class,
      Eastern Cooperative Oncology Group (ECOG) score, serum bilirubin level, and
      ethnicity. Multiple secondary independent variables were also measured. RESULTS.
      Of 239 consecutive patients treated during the prescribed time frame, 43 patients
      met the inclusion criteria. Thirty patients met the criteria for BCLC stage C,
      and 13 met the criteria for BCLC stage D based largely on ECOG score. Eight
      patients had venous invasion or portal venous thrombosis, and four had limited
      extrahepatic metastases. Eight patients had Child-Pugh class C liver disease but
      remained candidates for liver transplant based on the Milan criteria. The median
      overall survival was 596 days; 23 patients are still alive, 12 of whom underwent
      liver transplant. The only independent variables affecting survival were serum
      bilirubin value of 2.0 mg/dL or greater (hazard ratio [HR] = 3.96; 95% CI, 1.46
      10.7; p = 0.007) and Child-Pugh class B or C disease (HR = 3.33; 95% CI, 1.07
      10.34; p = 0.037). CONCLUSION. The use of DEBs for TACE therapy is safe and
      effective in carefully selected patients with advanced HCC.

PMID- 25615769
TI  - Pelvic venous insufficiency: imaging diagnosis, treatment approaches, and
      therapeutic issues.
AB  - OBJECTIVE. The purposes of this article are to review the causes of pelvic
      congestion syndrome and the imaging used to make the diagnosis and to summarize
      the treatment options. CONCLUSION. Pelvic congestion syndrome is one of many
      causes of chronic pelvic pain. It is thought to arise from ovarian and pelvic
      venous incompetence. Findings from various noninvasive imaging studies, such as
      Doppler ultrasound and MRI, in association with the clinical symptoms are
      critical in establishing the diagnosis.

PMID- 25615771
TI  - Complex iatrogenic esophageal injuries: an imaging spectrum.

PMID- 25615772
TI  - Radiographic techniques, contrast, and noise in x-ray imaging.

PMID- 25615773
TI  - Basal cell carcinoma: a comprehensive review for the radiologist.
AB  - OBJECTIVE. Basal cell carcinoma (BCC) is the most common malignancy in the United
      States. The purpose of this article is to provide a comprehensive description of
      the clinicopathologic features, diagnostic workup, staging, treatment, and follow
      up of BCC. CONCLUSION. Radiology plays an important role in the evaluation and
      staging of locally advanced and metastatic BCC. MRI is the modality of choice for
      assessing perineural disease and is equivalent or superior to CT for evaluating
      bony involvement. CT and PET/CT are used to evaluate metastatic disease. 

PMID- 25615774
TI  - Alternative screening for dense breasts: MRI.
AB  - OBJECTIVE. The purpose of this article is to review the use of MRI in breast
      density measurement and breast cancer risk estimation and to discuss the role of
      MRI as an alternative screening to mammography for screening women with dense
      breasts. CONCLUSION. The potential of MRI for screening women with dense breasts
      remains controversial because of the paucity of clinical evidence, the
      possibility of overdiagnosis, and the cost-effectiveness of the technique in this
      population. Although methods of MRI measurement require standardization and
      automation, future addition of MRI density to risk models may positively impact
      their value. 

PMID- 25615775
TI  - High-resolution sonography for distinguishing neoplastic gallbladder polyps and
      staging gallbladder cancer.
AB  - OBJECTIVE. The purposes of this study were to compare staging accuracy of high
      resolution sonography (HRUS) with combined low- and high-MHz transducers with
      that of conventional sonography for gallbladder cancer and to investigate the
      differences in the imaging findings of neoplastic and nonneoplastic gallbladder
      polyps. MATERIALS AND METHODS. Our study included 37 surgically proven
      gallbladder cancer (T1a = 7, T1b = 2, T2 = 22, T3 = 6), including 15 malignant
      neoplastic polyps and 73 surgically proven polyps (neoplastic = 31, nonneoplastic
      = 42) that underwent HRUS and conventional transabdominal sonography. Two
      radiologists assessed T-category and predefined polyp findings on HRUS and
      conventional transabdominal sonography. Statistical analyses were performed using
      chi-square and McNemar tests. RESULTS. The diagnostic accuracy for the T category
      was T1a = 92-95%, T1b = 89-95%, T2 = 78-86%, and T3 = 84-89%, all with good
      agreement (kappa = 0.642) using HRUS. The diagnostic accuracy for differentiating
      T1 from T2 or greater than T2 was 92% and 89% on HRUS and 65% and 70% with
      conventional transabdominal sonography. Statistically common findings for
      neoplastic polyps included size greater than 1 cm, single lobular surface,
      vascular core, hypoechoic polyp, and hypoechoic foci (p < 0.05). The value of
      HRUS in the differential diagnosis of a gallbladder polyp was more clearly
      depicted internal echo foci than conventional transabdominal sonography (39 vs
      21). A polyp size greater than 1 cm was independently associated with a
      neoplastic polyp (odds ratio = 7.5, p = 0.02). The AUC of a polyp size greater
      than 1 cm was 0.877. The sensitivity and specificity were 66.67% and 89.13%,
      respectively. CONCLUSION. HRUS is a simple method that enables accurate T
      categorization of gallbladder carcinoma. It provides high-resolution images of
      gallbladder polyps and may have a role in stratifying the risk for malignancy. 

PMID- 25615776
TI  - Does gadolinium-based contrast material improve diagnostic accuracy of local
      invasion in rectal cancer MRI? A multireader study.
AB  - OBJECTIVE. The purpose of this study was to compare reader accuracy and agreement
      on rectal MRI with and without gadolinium administration in the detection of T4
      rectal cancer. MATERIALS AND METHODS. In this study, two radiologists and one
      fellow independently interpreted all posttreatment MRI studies for patients with
      locally advanced or recurrent rectal cancer using unenhanced images alone or
      combined with contrast-enhanced images, with a minimum interval of 4 weeks.
      Readers evaluated involvement of surrounding structures on a 5-point scale and
      were blinded to pathology and disease stage. Sensitivity, specificity, negative
      predictive value, positive predictive value, and AUC were calculated and kappa
      statistics were used to describe interreader agreement. RESULTS. Seventy-two
      patients (38 men and 34 women) with a mean age of 61 years (range, 32-86 years)
      were evaluated. Fifteen patients had 32 organs invaded. Global AUCs without and
      with gadolinium administration were 0.79 and 0.77, 0.91 and 0.86, and 0.83 and
      0.78 for readers 1, 2, and 3, respectively. AUCs before and after gadolinium
      administration were similar. Kappa values before and after gadolinium
      administration for pairs of readers ranged from 0.5 to 0.7. CONCLUSION. On the
      basis of pathology as a reference standard, the use of gadolinium during rectal
      MRI did not significantly improve radiologists' agreement or ability to detect T4
      disease. 

PMID- 25615777
TI  - Extracapsular extension in prostate cancer: added value of diffusion-weighted MRI
      in patients with equivocal findings on T2-weighted imaging.
AB  - OBJECTIVE. The objective of our study was to evaluate diffusion-weighted imaging
      (DWI) and T2-weighted imaging for predicting extracapsular extension (ECE) in
      patients with prostate cancer. MATERIALS AND METHODS. One hundred seventeen
      patients underwent preoperative 3-T MRI and radical prostatectomy. Two
      radiologists evaluated ECE with T2-weighted imaging based on the Prostate Imaging
      Reporting and Data System (PI-RADS). Then, the apparent diffusion coefficient
      (ADC) of the tumor calculated from two b values (0, 1000 s/mm(2)) was measured.
      Interreader agreement of T2-weighted imaging scores was assessed with weighted
      kappa statistics. We compared T2-weighted imaging scores and ADC values between
      patients with ECE and those without ECE using the unpaired Student t test and
      evaluated their association with ECE using logistic regression analyses and ROC
      curves incorporating prostate-specific antigen value, Gleason score, clinical
      stage, and greatest percentage involved core length. The ADC values were also
      tested for differences between patients with ECE and those without ECE in
      subgroups stratified by the T2-weighted imaging criteria shown to have a high
      specificity for ECE. RESULTS. Fifty (42.7%) patients had ECE. There was
      substantial agreement for T2-weighted imaging scores (kappa = 0.613). T2-weighted
      imaging scores and ADCs were significantly different in patients with ECE and
      those without ECE (p < 0.001). Multivariate analysis showed that the greatest
      percentage involved core length, T2-weighted imaging score, and ADC (p < 0.05)
      were independently predictive of ECE. The AUCs for these variables (range, 0.733
      0.770) were not significantly different except for the AUC for clinical stage
      (0.552). The use of a high specificity (92.5%) setting for ECE divided the
      patients into the following groups: patients with a T2-weighted imaging score of
      >= 4 (n = 20) and patients with a T2-weighted imaging score of < 4 (n = 97). In
      patients with a T2-weighted imaging score of >= 4, the ADC was not significantly
      different between patients with ECE and those without ECE (p = 0.555). However,
      among patients with a T2-weighted imaging score of <= 3, the ADC value was
      significantly lower in patients with ECE (mean +/- SD, 0.794 +/- 0.116) than in
      those without ECE (1.027 +/- 0.339) (p < 0.001). CONCLUSION. T2-weighted imaging
      scores and ADCs were independently associated with ECE, and the ADC had
      incremental value in patients without a high suspicion of ECE on T2-weighted
      imaging. 

PMID- 25615778
TI  - A quantitative comparison of noise reduction across five commercial (hybrid and
      model-based) iterative reconstruction techniques: an anthropomorphic phantom
      study.
AB  - OBJECTIVE. The objective of our study was to compare the performance of three
      hybrid iterative reconstruction techniques (IRTs) (ASiR, iDose4, SAFIRE) and
      their respective strengths for image noise reduction on low-dose CT examinations
      using filtered back projection (FBP) as the standard reference. Also, we compared
      the performance of these three hybrid IRTs with two model-based IRTs (Veo and
      IMR) for image noise reduction on low-dose examinations. MATERIALS AND METHODS.
      An anthropomorphic abdomen phantom was scanned at 100 and 120 kVp and different
      tube current-exposure time products (25-100 mAs) on three CT systems (for ASiR
      and Veo, Discovery CT750 HD; for iDose4 and IMR, Brilliance iCT; and for SAFIRE,
      Somatom Definition Flash). Images were reconstructed using FBP and using IRTs at
      various strengths. Nine noise measurements (mean ROI size, 423 mm(2)) on
      extracolonic fat for the different strengths of IRTs were recorded and compared
      with FBP using ANOVA. Radiation dose, which was measured as the volume CT dose
      index and dose-length product, was also compared. RESULTS. There were no
      significant differences in radiation dose and image noise among the scanners when
      FBP was used (p > 0.05). Gradual image noise reduction was observed with each
      increasing increment of hybrid IRT strength, with a maximum noise suppression of
      approximately 50% (48.2-53.9%). Similar noise reduction was achieved on the
      scanners by applying specific hybrid IRT strengths. Maximum noise reduction was
      higher on model-based IRTs (68.3-81.1%) than hybrid IRTs (48.2-53.9%) (p < 0.05).
      CONCLUSION. When constant scanning parameters are used, radiation dose and image
      noise on FBP are similar for CT scanners made by different manufacturers.
      Significant image noise reduction is achieved on low-dose CT examinations
      rendered with IRTs. The image noise on various scanners can be matched by
      applying specific hybrid IRT strengths. Model-based IRTs attain substantially
      higher noise reduction than hybrid IRTs irrespective of the radiation dose. 

PMID- 25615779
TI  - CT angiography of neonates and infants: comparison of radiation dose and image
      quality of target mode prospectively ECG-gated 320-MDCT and ungated helical 64
      MDCT.
AB  - OBJECTIVE. The purpose of this study was to evaluate the radiation dose and image
      quality of target mode prospectively ECG-gated volumetric CT angiography (CTA)
      performed with a 320-MDCT scanner compared with the radiation dose and image
      quality of ungated helical CTA performed with a 64-MDCT scanner. MATERIALS AND
      METHODS. An experience with CTA for cardiovascular indications in neonates and
      infants 0-6 months old was retrospectively assessed. Radiation doses and
      quantitative and qualitative image quality scores of 28 CTA examinations
      performed with a 320-MDCT scanner and volumetric target mode prospective ECG
      gating plus iterative reconstruction (target mode) were compared with the doses
      and scores of 28 CTA examinations performed with a 64-MDCT scanner and ungated
      helical scanning plus filtered back projection reconstruction (ungated mode). All
      target mode studies were performed during free breathing. Seven ungated CTA
      examinations (25%) were performed with general endotracheal anesthesia. The
      findings of 17 preoperative CTA examinations performed in target mode were also
      compared with surgical reports for evaluation of diagnostic accuracy. RESULTS.
      All studies performed with target mode technique were diagnostic for the main
      clinical indication. Effective doses were significantly lower in the target mode
      group (0.51 +/- 0.19 mSv) compared with the ungated mode group (4.8 +/- 1.4 mSv)
      (p < 0.0001). Quantitative analysis revealed no statistically significant
      difference between the two groups with respect to signal-to-noise ratio (of
      pulmonary artery and aorta) and contrast-to-noise ratio. Subjective image quality
      was significantly better with target mode than with ungated mode (p < 0.0001).
      CONCLUSION. Target mode prospectively ECG-gated volumetric scanning with
      iterative reconstruction performed with a 320-MDCT scanner has several benefits
      in cardiovascular imaging of neonates and infants, including low radiation dose,
      improved image quality, high diagnostic accuracy, and ability to perform free
      breathing studies. 

PMID- 25615780
TI  - Distal humeral epiphyseal separation in young children: an often-missed fracture
      radiographic signs and ultrasound confirmatory diagnosis.
AB  - OBJECTIVE. Distal humeral epiphyseal separation is rare and often misdiagnosed.
      The purpose of this study was to summarize an experience with radiography and
      ultrasound of distal humeral epiphyseal separation. MATERIALS AND METHODS. The
      records of all children younger than 36 months with the diagnosis of distal
      humeral epiphyseal separation from 2006 to 2013 were identified. Medical and
      imaging records were reviewed for diagnosis with radiography and ultrasound,
      cause, treatment, and follow-up. The initial diagnosis, relation of the radius
      and ulna to the distal humerus, presence of other fractures, and signs of elbow
      effusion were evaluated. RESULTS. Sixteen patients (10 boys, six girls; mean age,
      8.6 months) were evaluated for distal humeral epiphyseal separation. All patients
      had elbow radiographs. Fifteen (94%) patients had medial and six (38%) had
      posterior displacement of the radius and ulna. The diagnosis was missed on
      radiographs of nine (56%) patients. Ultrasound was performed for 12 patients and
      showed distal humeral epiphyseal separation in all. In 10 (63%) patients, one or
      more additional humeral fractures were found: bucket-handle fractures in five
      patients and condylar avulsion fracture in six patients. In the six (38%)
      patients younger than 1 month, distal humeral epiphyseal separation was secondary
      to birth trauma. In 4 of the 10 (40%) older patients, nonaccidental trauma was
      diagnosed. All patients underwent follow-up with a pediatric orthopedist and had
      full range of motion. Two patients had mild varus deformities. CONCLUSION. The
      diagnosis of distal humeral epiphyseal separation is often missed on radiographs.
      Radiologists should be aware that posteromedial displacement of the radius and
      ulna in young children is highly suggestive of distal humeral epiphyseal
      separation and that the diagnosis can be confirmed with ultrasound. 

PMID- 25615781
TI  - Brachial plexus birth palsy: multimodality imaging of spine and shoulder
      abnormalities in children.
AB  - OBJECTIVE. The purpose of this article is to provide a comprehensive overview of
      the imaging of brachial plexus palsy, including both pathologic conditions of the
      spine and shoulder and clinical background and management. CONCLUSION. Brachial
      plexus birth palsy can result in permanent disability and limb deformity.
      Identifying the lesion type and associated sequelae is important in clinical
      management aimed at optimizing outcome. The imaging algorithms used are guided by
      clinical presentation and are designed to assess the extent of injury to guide
      possible surgical intervention. 

PMID- 25615782
TI  - CT-guided implantation of intrahepatic fiducial markers for proton beam therapy
      of liver lesions: assessment of success rate and complications.
AB  - OBJECTIVE. The purpose of this study is to evaluate the safety and complications
      of CT-guided implantation of intrahepatic fiducial markers for proton beam
      therapy. MATERIALS AND METHODS. In this retrospective study, we reviewed 69
      patients who underwent 149 percutaneous fiducial marker implantations for primary
      and metastatic hepatic tumors from April 2007 through July 2013. The
      implantations enabling satisfactory treatment planning and CT simulation were
      considered as technically successful. Major and minor procedure-related
      complications during and after fiducial marker implantation were documented.
      RESULTS. The success rate of fiducial marker implantation was 99.3% (148/149). In
      one patient, a fiducial marker migrated into the vascular system, which was
      realized during the procedure and required reimplantation. None of the patients
      was required to return for additional implantations. The major and minor
      complication rates were 0% and 2.9% (2/69), respectively. Both minor
      complications included small pneumothorax not requiring hospital admission.
      CONCLUSION. CT-guided placement of gold fiducial markers is associated with a
      high technical success rate with few complications, which is an essential step in
      the overall treatment planning and performance of proton beam therapy for the
      management of hepatic tumors. 

PMID- 25615783
TI  - MEDICOLEGAL-malpractice and ethical issues in radiology. "Normal" versus
      "unremarkable" versus "within normal limits.".

PMID- 25615784
TI  - MEDICOLEGAL-malpractice and ethical issues in radiology. Daubert hearing.

PMID- 25615785
TI  - Fat-suppressed T2-weighted MRI for diagnosis of angiomyolipoma without visible
      fat.

PMID- 25615786
TI  - Time-driven activity-based costing trumps traditional cost accounting for
      radiologists.

PMID- 25615787
TI  - Accuracy of ultrasound of musculoskeletal soft-tissue tumors.

PMID- 25615788
TI  - Reply to "accuracy of ultrasound of musculoskeletal soft-tissue tumors".

PMID- 25615789
TI  - Ultrasound accuracy in the diagnosis of skin and soft-tissue lesions.

PMID- 25615790
TI  - Reply to "ultrasound accuracy in the diagnosis of skin and soft-tissue lesions".

PMID- 25615791
TI  - The sonographic multilaminar appearance is not enough for the diagnosis of
      enteric duplication cyst in children.

PMID- 25615792
TI  - Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and
      left ventricular remodeling after myocardial infarction in rabbits.
AB  - Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase activity and
      endoplasmic reticulum (ER) stress are increased after myocardial infarction (MI).
      In this study, we proposed to test whether activation of the NADPH oxidase in the
      remote non-infarcted myocardium mediates ER stress and left ventricular (LV)
      remodeling after MI. Rabbits with MI or sham operation were randomly assigned to
      orally receive an NADPH oxidase inhibitor apocynin or placebo for 30 days. The
      agents were administered beginning at 1 week after surgery. MI rabbits exhibited
      decreases in LV fractional shortening, LV ejection fraction and the first
      derivative of the LV pressure rise, which were abolished by apocynin treatment.
      NADPH oxidase Nox2 protein and mRNA expressions were increased in the remote non
      infarcted myocardium after MI. Immunolabeling further revealed that Nox2 was
      increased in cardiac myocytes in the remote myocardium. The apocynin treatment
      prevented increases in the Nox2 expression, NADPH oxidase activity, oxidative
      stress, myocyte apoptosis and GRP78, CHOP and cleaved caspase 12 protein
      expression in the remote myocardium. The apocynin treatment also attenuated
      increases in myocyte diameter and cardiac fibrosis. In cultured H9C2
      cardiomyocytes exposed to angiotensin II, an important stimulus for post-MI
      remodeling, Nox2 knockdown with siRNA significantly inhibited angiotensin II
      induced NADPH oxidase activation, reactive oxygen species and GRP78 and CHOP
      protein expression. We conclude that NADPH oxidase inhibition attenuates
      increased ER stress in the remote non-infarcted myocardium and LV remodeling late
      after MI in rabbits. These findings suggest that the activation of NADPH oxidase
      in the remote non-infarcted myocardium mediates increased ER stress, contributing
      to myocyte apoptosis and LV remodeling after MI.

PMID- 25615793
TI  - Sarcoplasmic reticulum Ca2+ ATPase pump is a major regulator of glucose transport
      in the healthy and diabetic heart.
AB  - Despite intensive research, the pathways that mediate calcium (Ca(2+))-stimulated
      glucose transport in striated muscle remain elusive. Since the sarcoplasmic
      reticulum calcium ATPase (SERCA) pump tightly regulates cytosolic [Ca(2+)], we
      investigated whether the SERCA pump is a major regulator of cardiac glucose
      transport. We used healthy and insulin-deficient diabetic transgenic (TG) mice
      expressing SERCA1a in the heart. Active cell surface glucose transporter (GLUT)-4
      was measured by a biotinylated photolabeled assay in the intact perfused
      myocardium and isolated myocytes. In healthy TG mice, cardiac-specific SERCA1a
      expression increased active cell-surface GLUT4 and glucose uptake in the
      myocardium, as well as whole body glucose tolerance. Diabetes reduced active cell
      surface GLUT4 content and glucose uptake in the heart of wild type mice, all of
      which were preserved in diabetic TG mice. Decreased basal AS160 and increased
      proportion of calmodulin-bound AS160 paralleled the increase in cell surface
      GLUT4 content in the heart of TG mice, suggesting that AS160 regulates GLUT
      trafficking by a Ca(2+)/calmodulin dependent pathway. In addition, cardiac
      specific SERCA1a expression partially rescues hyperglycemia during diabetes.
      Collectively, these data suggested that the SERCA pump is a major regulator of
      cardiac glucose transport by an AS160 dependent mechanism during healthy and
      insulin-deficient state. Our data further indicated that cardiac-specific SERCA
      overexpression rescues diabetes induced-alterations in cardiac glucose transport
      and improves whole body glucose homeostasis. Therefore, findings from this study
      provide novel mechanistic insights linking upregulation of the SERCA pump in the
      heart as a potential therapeutic target to improve glucose metabolism during
      diabetes. 

PMID- 25615795
TI  - Mental health disorders after traumatic brain injury in a New Zealand caseload.
AB  - PRIMARY OBJECTIVE: This study investigated psychological disorders for patients
      receiving traumatic brain injury (TBI) rehabilitation within a community-based
      TBI service in New Zealand. RESEARCH DESIGN: Cross-sectional study involving
      retrospective review of clinical notes for all referrals received in a 6-month
      period. This methodology was selected to gain a sample of individuals reflective
      of the range of patients seen in TBI rehabilitation services in New Zealand.
      METHODS AND PROCEDURES: The clinical records for 279 patients were reviewed for
      formal psychiatric diagnoses and references to moderate or severe psychological
      symptoms. MAIN OUTCOMES AND RESULTS: Of the clinical records, 57.7% noted
      significant psychological problems post-injury (n = 161) and 8.6% had a
      psychiatric diagnosis recorded, with 10.8% reporting psychological disorders pre
      injury. In comparison, 15.1% had input from a clinical psychologist and 2.2% had
      involvement from a mental health team. CONCLUSIONS: The rate of psychological
      symptoms was significantly higher post-TBI than pre-TBI and few of the patients
      reporting significant psychological symptoms were receiving intervention from
      mental health professionals. Further research is needed regarding the ability of
      TBI rehabilitation professionals in New Zealand to identify and respond to the
      psychological implications of TBI and on the ability of TBI and mental health
      teams to liaise effectively.

PMID- 25615794
TI  - Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial
      dysfunction and epigenetic modifications.
AB  - HHcy has been implicated in elderly frailty, but the underlying mechanisms are
      poorly understood. Using C57 and CBS+/- mice and C2C12 cell line, we investigated
      mechanisms behind HHcy induced skeletal muscle weakness and fatigability.
      Possible alterations in metabolic capacity (levels of LDH, CS, MM-CK and COX-IV),
      in structural proteins (levels of dystrophin) and in mitochondrial function (ATP
      production) were examined. An exercise regimen was employed to reverse HHcy
      induced changes. CBS+/- mice exhibited more fatigability, and generated less
      contraction force. No significant changes in muscle morphology were observed.
      However, there is a corresponding reduction in large muscle fiber number in CBS+/
      mice. Excess fatigability was not due to changes in key enzymes involved in
      metabolism, but was due to reduced ATP levels. A marginal reduction in dystrophin
      levels along with a decrease in mitochondrial transcription factor A (mtTFA) were
      observed. There was also an increase in the mir-31, and mir-494 quantities that
      were implicated in dystrophin and mtTFA regulation respectively. The molecular
      changes elevated during HHcy, with the exception of dystrophin levels, were
      reversed after exercise. In addition, the amount of NRF-1, one of the
      transcriptional regulators of mtTFA, was significantly decreased. Furthermore,
      there was enhancement in mir-494 levels and a concomitant decline in mtTFA
      protein quantity in homocysteine treated cells. These changes in C2C12 cells were
      also accompanied by an increase in DNMT3a and DNMT3b proteins and global DNA
      methylation levels. Together, these results suggest that HHcy plays a causal role
      in enhanced fatigability through mitochondrial dysfunction which involves
      epigenetic changes.

PMID- 25615796
TI  - Design, synthesis and biological evaluations of chirally pure 1,2,3,4
      tertrahydroisoquinoline analogs as anti-cancer agents.
AB  - A series of fifteen chiral 1,2,3,4-tetrahydroisoquinoline (THIQ) derivatives have
      been synthesized and their antiproliferative properties have been studied. The in
      vitro screening was performed against five cancer cell lines; MCF-7 (breast
      cancer), A549 (lung cancer), DU-145 (prostate cancer), Hela (cervical cancer) and
      HepG2 (liver cancer). Most of the compounds showed promising activity with IC50
      Values ranging from 0.72 to 92.6 MUM. Among them, compounds 9a and 9b have shown
      significant activity against human prostate cancer cell line, i.e., DU-145 with
      IC50 value 0.72 and 1.23 MUM respectively. To investigate the mechanism of
      action, detailed biological studies of compounds 9a and 9b were carried out on
      the human prostate cancer cell line, DU-145. Flow cytometric analysis revealed
      that these compounds induced cell cycle arrest at G2/M phase. Tubulin
      polymerization assay and immunofluorescence analysis results suggested that these
      compounds effectively inhibit microtubule assembly formation in DU-145. The
      apoptosis inducing properties were evaluated by DNA fragmentation analysis,
      Caspase-3 activity assay, Annexin V-FITC assay and Western blot analysis of
      proapoptotic protein, Bax and antiapoptotic protein Bcl-2. 

PMID- 25615797
TI  - Small molecules inhibitors of plasminogen activator inhibitor-1 - an overview.
AB  - PAI-1, a glycoprotein from the serpin family and the main inhibitor of tPA and
      uPA, plays an essential role in the regulation of intra and extravascular
      fibrinolysis by inhibiting the formation of plasmin from plasminogen. PAI-1 is
      also involved in pathological processes such as thromboembolic diseases,
      atherosclerosis, fibrosis and cancer. The inhibition of PAI-1 activity by small
      organic molecules has been observed in vitro and with some in vivo models. Based
      on these findings, PAI-1 appears as a potential therapeutic target for several
      pathological conditions. Over the past decades, many efforts have therefore been
      devoted to developing PAI-1 inhibitors. This article provides an overview of the
      publishing activity on small organic molecules used as PAI-1 inhibitors. The
      chemical synthesis of the most potent inhibitors as well as their biological and
      biochemical evaluations is also presented. 

PMID- 25615798
TI  - Corrigendum: Identifying signatures of photothermal current in a double-gated
      semiconducting nanotube.

PMID- 25615799
TI  - Cooperative loading and release behavior of a metal-organic receptor.
AB  - In order to design artificial chemical systems that are capable of achieving
      complex functions, it is useful to design synthetic receptors that mimic their
      biological counterparts. Biological functions are underpinned by properties that
      include specific binding with high affinity and selectivity, cooperativity, and
      release triggered by external stimuli. Here we show that a metal-organic receptor
      constructed through subcomponent self-assembly can selectively and cooperatively
      load and release oxocarbon anions. The flexible coordination spheres of its
      cadmium(II) centers allow the receptor to dynamically adjust its structure upon
      exchanging four triflate or triflimide counterions for two oxocarbon anions,
      resulting in strong cooperativity and very tight binding, with an apparent
      association constant for C5O5(2-) of 5 * 10(10) M(-1). Substituting the
      cadmium(II) ions for copper(I) by switching solvent prompted a structural
      reorganization and release of the oxocarbon anions. Its cooperative behavior
      allows the receptor to carry a greater payload than would be possible in a
      noncooperative analogue. 

PMID- 25615800
TI  - Impact of an integrated model of care on potentially preventable hospitalizations
      for people with Type 2 diabetes mellitus.
AB  - AIMS: To evaluate the impact of an integrated model of care for patients with
      complex Type 2 diabetes mellitus on potentially preventable hospitalizations.
      METHODS: A prospective controlled trial was conducted comparing a
      multidisciplinary, community-based, integrated primary-secondary care diabetes
      service with usual care at a hospital diabetes outpatient clinic. Study and
      hospital admissions data were linked for the period from 12 months before to 24
      months after commencement of the trial. The primary outcome was the number of
      potentially preventable hospitalizations with diabetes-related principal
      diagnoses. Length of stay once hospitalized was also reported. RESULTS: Of 327
      adult participants, 206 were hospitalized and accounted for 667 admissions during
      the study period. Compared with the usual care group, patients in the integrated
      model of care group were nearly half as likely to be hospitalized for a
      potentially preventable diabetes-related principal diagnosis in the 24 months
      after study commencement (incidence rate ratio 0.53, 95% CI 0.29, 0.96; P =
      0.04). The magnitude of the result remained similar after adjusting for age, sex,
      education and baseline HbA1c concentration (incidence rate ratio 0.54, 95% CI
      0.29, 1.01; P = 0.05).When hospitalized, patients in the integrated care group
      had a similar length of stay compared with those in the usual care group (median
      difference -2 days, 95% CI -6.5, 2.3; P = 0.33). CONCLUSIONS: Patients receiving
      the integrated model of care had a reduction in the number of hospitalizations
      when the principal diagnosis for admission was a diabetes-related complication.
      Integrated models of care for people with complex diabetes can reduce
      hospitalizations and help attempts to curtail increasing demand on finite health
      services.

PMID- 25615802
TI  - Development and content validity of a screening instrument for gaming addiction
      in adolescents: the Gaming Addiction Identification Test (GAIT).
AB  - This study describes the development of a screening tool for gaming addiction in
      adolescents - the Gaming Addiction Identification Test (GAIT). Its development
      was based on the research literature on gaming and addiction. An expert panel
      comprising professional raters (n = 7), experiential adolescent raters (n = 10),
      and parent raters (n = 10) estimated the content validity of each item (I-CVI) as
      well as of the whole scale (S-CVI/Ave), and participated in a cognitive interview
      about the GAIT scale. The mean scores for both I-CVI and S-CVI/Ave ranged between
      0.97 and 0.99 compared with the lowest recommended I-CVI value of 0.78 and the S
      CVI/Ave value of 0.90. There were no sex differences and no differences between
      expert groups regarding ratings in content validity. No differences in the
      overall evaluation of the scale emerged in the cognitive interviews. Our
      conclusions were that GAIT showed good content validity in capturing gaming
      addiction. The GAIT needs further investigation into its psychometric properties
      of construct validity (convergent and divergent validity) and criterion-related
      validity, as well as its reliability in both clinical settings and in community
      settings with adolescents. 

PMID- 25615801
TI  - Functional diversity enhances the resistance of ecosystem multifunctionality to
      aridity in Mediterranean drylands.
AB  - We used a functional trait-based approach to assess the impacts of aridity and
      shrub encroachment on the functional structure of Mediterranean dryland
      communities (functional diversity (FD) and community-weighted mean trait values
      (CWM)), and to evaluate how these functional attributes ultimately affect
      multifunctionality (i.e. the provision of several ecosystem functions
      simultaneously). Shrub encroachment (the increase in the abundance/cover of
      shrubs) is a major land cover change that is taking place in grasslands
      worldwide. Studies conducted on drylands have reported positive or negative
      impacts of shrub encroachment depending on the functions and the traits of the
      sprouting or nonsprouting shrub species considered. FD and CWM were equally
      important as drivers of multifunctionality responses to both aridity and shrub
      encroachment. Size traits (e.g. vegetative height or lateral spread) and leaf
      traits (e.g. specific leaf area and leaf dry matter content) captured the effect
      of shrub encroachment on multifunctionality with a relative high accuracy (r(2) 
      = 0.63). FD also improved the resistance of multifunctionality along the aridity
      gradient studied. Maintaining and enhancing FD in plant communities may help to
      buffer negative effects of ongoing global environmental change on dryland
      multifunctionality. 

PMID- 25615803
TI  - Evaluation of medicine effects on the interaction of myoglobin and its aptamer or
      antibody using atomic force microscopy.
AB  - The effects of medicine on the biomolecular interaction have been given
      increasing attention in biochemistry and affinity-based analytics since the
      environment in vivo is complex especially for the patients. Herein, myoglobin, a
      biomarker of acute myocardial infarction, was used as a model, and the medicine
      effects on the interactions of myoglobin/aptamer and myoglobin/antibody were
      systematically investigated using atomic force microscopy (AFM) for the first
      time. The results showed that the average binding force and the binding
      probability of myoglobin/aptamer almost remained unchanged after myoglobin
      modified gold substrate was incubated with promazine, amoxicillin, aspirin, and
      sodium penicillin, respectively. These parameters were changed for
      myoglobin/antibody after the myoglobin-modified gold substrate was treated with
      these medicines. For promazine and amoxicillin, they resulted in the change of
      binding force distribution of myoglobin/antibody (i.e., from unimodal
      distribution to bimodal distribution) and the increase of binding probability;
      for aspirin, it only resulted in the change of the binding force distribution,
      and for sodium penicillin, it resulted in the increase of the average binding
      force and the binding probability. These results may be attributed to the
      different interaction modes and binding sites between myoglobin/aptamer and
      myoglobin/antibody, the different structures between aptamer and antibody, and
      the effects of medicines on the conformations of myoglobin. These findings could
      enrich our understanding of medicine effects on the interactions of aptamer and
      antibody to their target proteins. Moreover, this work will lay a good foundation
      for better research and extensive applications of biomolecular interaction,
      especially in the design of biosensors in complex systems. 

PMID- 25615804
TI  - Testing the mean matrix in high-dimensional transposable data.
AB  - The structural information in high-dimensional transposable data allows us to
      write the data recorded for each subject in a matrix such that both the rows and
      the columns correspond to variables of interest. One important problem is to test
      the null hypothesis that the mean matrix has a particular structure without
      ignoring the dependence structure among and/or between the row and column
      variables. To address this, we develop a generic and computationally inexpensive
      nonparametric testing procedure to assess the hypothesis that, in each predefined
      subset of columns (rows), the column (row) mean vector remains constant. In
      simulation studies, the proposed testing procedure seems to have good performance
      and, unlike simple practical approaches, it preserves the nominal size and
      remains powerful even if the row and/or column variables are not independent.
      Finally, we illustrate the use of the proposed methodology via two empirical
      examples from gene expression microarrays. 

PMID- 25615806
TI  - Tuberculous uveitis.

PMID- 25615807
TI  - Clinics of ocular tuberculosis.
AB  - PURPOSE: Ocular tuberculosis is an extrapulmonary tuberculous condition and has
      variable manifestations. The purpose of this review is to describe the clinical
      manifestations of ocular tuberculosis affecting the anterior and posterior
      segments of the eye in both immunocompetent and immunocompromised patients.
      METHODS: Review of literature using Pubmed database. RESULTS: Mycobacterium
      tuberculosis may lead to formation of conjunctival granuloma, nodular scleritis,
      and interstitial keratitis. Lacrimal gland and orbital caseating granulomas are
      rare but may occur. The intraocular structures are also a target of insult by M.
      tuberculosis and may cause anterior granulomatous uveitis, anterior and posterior
      synechiae, secondary glaucoma, and cataract. The bacillus may involve the ciliary
      body, resulting in the formation of a localized caseating granuloma. Posterior
      segment manifestations include vitritis, retinal vasculitis, optic neuritis,
      serpiginous-like choroiditis, choroidal tubercules, subretinal
      neovascularization, and, rarely, endophthalmitis. CONCLUSIONS: The recognition of
      clinical signs of ocular tuberculosis is of utmost importance as it can provide
      clinical pathway toward tailored investigations and decision making for
      initiating anti-tuberculosis therapy.

PMID- 25615808
TI  - Diagnosis and treatment for ocular tuberculosis among uveitis specialists: the
      international perspective.
AB  - PURPOSE: To assess the approach of international specialists, who primarily
      practice in tuberculosis-endemic areas, to ocular tuberculosis (TB). METHODS:
      International experts from India, Brazil, Taiwan, and more than 10 other
      countries were surveyed using two clinical cases and general questions. RESULTS:
      A total of 244 experts were sent a survey about the treatment and diagnosis of
      ocular tuberculosis; 65 responded (27%), of whom 34 were affiliated with
      practices in India, while 31 primarily practice at international sites outside of
      India and North America. The data from this survey were compared with the results
      of a similar survey sent to members of the American Uveitis Society. The survey
      provided normative data on how physicians evaluate patients with uveitis as well
      as opinions about ocular TB. Responses varied widely on topics such as tests to
      include in the workup of undifferentiated uveitis, initial therapy, and duration
      of treatment. Physicians from developing countries relied more on chest CT scans
      and tuberculin skin testing (TST) than their counterparts in developed countries.
      CONCLUSIONS: The approach to diagnosis and management of TB is heterogeneous
      worldwide. However, there are substantial differences in the clinical approach to
      uveitis depending on the clinician's location of practice.

PMID- 25615809
TI  - The role of anti-tubercular therapy in patients with presumed ocular
      tuberculosis.
AB  - OBJECTIVE: To analyze the factors affecting the treatment outcome in patients
      with presumed ocular tuberculosis on anti-tubercular therapy (ATT). METHODS:
      Retrospective chart review of patients with presumed ocular tuberculosis seen at
      a tertiary referral eye care center in the United Kingdom. Failure was defined as
      recurrence of inflammation within 6 months of completion of ATT. RESULTS: There
      were a total of 175 patients with presumed ocular tuberculosis who had ATT.
      Patients with intermediate uveitis or panuveitis and those on immunosuppressive
      therapy had higher odds of treatment failure (p < 0.05) while those with more
      than 9 months of ATT (77, 79.38%) had less likelihood of failure. CONCLUSION: We
      present the largest case series of patients with presumed ocular tuberculosis in
      a low endemic area treated with ATT. Longer duration of treatment resulted in
      reduced risk of recurrence of inflammation, whereas immunosuppression adversely
      affected the final treatment outcome.

PMID- 25615810
TI  - devR PCR for the diagnosis of intraocular tuberculosis.
AB  - PURPOSE: To compare the efficacy of devR and MPB64 PCR in the diagnosis of
      intraocular tuberculosis. METHODS: Prospective, nonrandomized study. Seventy-five
      patients were enrolled in 3 groups. Group A had 25 patients with presumed
      intraocular tubercular uveitis, group B had 25 controls with specific uveitis
      other than tubercular uveitis, and group C included 25 non-uveitic negative
      controls. The undiluted vitreous/aqueous samples were collected and subjected to
      PCR assay for devR and MPB64 gene sequence of Mycobacterium tuberculosis (MTB) to
      detect sensitivity and specificity. RESULTS: devR PCR was positive in 16 (64%)
      out of 25 patients with presumed tubercular uveitis. MPB64 PCR was positive in 18
      (72%) out of 25 patients with presumed tubercular uveitis. The sensitivity and
      specificity of devR were 64 and 100%, respectively. The sensitivity and
      specificity of MPB64 PCR were 72 and 100%, respectively. CONCLUSION: devR PCR is
      not a better tool than MPB64 PCR for diagnosing intraocular tuberculosis.

PMID- 25615811
TI  - An examination of violence risk communication in practice using a structured
      professional judgment framework.
AB  - The increased use of violence risk assessment tools in professional practice has
      sparked the development of best-practice guidelines for communicating about
      violence risk. The present study examined 166 pre-sentence reports, authored by
      clinicians and probation officers, to determine the extent to which they are
      consistent with those guidelines. We examined the frequency with which reports
      contained information about five topics: the presence of risk factors; the
      relevance of risk factors; scenarios of future violence; recommended management
      strategies; and summary risk judgments. Analyses revealed that the topics
      addressed most frequently in reports were the presence of risk factors and
      recommended management strategies, but none of the five topics was addressed
      consistently, completely, or clearly in reports. This was especially the case for
      probation reports. The findings highlight the need to improve practice through
      better implementation of guidelines for risk communication. Also needed is
      research on the extent to which information in risk communications is
      comprehended, accepted, and used by various stakeholder groups.

PMID- 25615812
TI  - On maps, shapeshifting, and my syllabus: family therapies today.

PMID- 25615817
TI  - X-chromosomal inactivation directly influences the phenotypic manifestation of X
      linked protoporphyria.
AB  - X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from
      terminal exon gain-of-function mutations in the ALAS2 gene causing increased
      ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients
      present with severe cutaneous photosensitivity and may develop liver dysfunction.
      XLP was originally reported as X-linked dominant with 100% penetrance in males
      and females. We characterized 11 heterozygous females from six unrelated XLP
      families and show markedly varying phenotypic and biochemical heterogeneity,
      reflecting the degree of X-chromosomal inactivation of the mutant gene. ALAS2
      sequencing identified the specific mutation and confirmed heterozygosity among
      the females. Clinical history, plasma and erythrocyte protoporphyrin levels were
      determined. Methylation assays of the androgen receptor and zinc-finger MYM type
      3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal
      inactivation pattern. Heterozygotes with equal or increased skewing, favoring
      expression of the wild-type allele had no clinical symptoms and only slightly
      increased erythrocyte protoporphyrin concentrations and/or frequency of
      protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele
      was preferentially inactivated, heterozygous females manifested the disease
      phenotype and had both higher erythrocyte protoporphyrin levels and circulating
      fluorocytes. These findings confirm that the previous dominant classification of
      XLP is inappropriate and genetically misleading, as the disorder is more
      appropriately designated XLP.

PMID- 25615818
TI  - Functional cyclic AMP response element in the breast cancer resistance protein
      (BCRP/ABCG2) promoter modulates epidermal growth factor receptor pathway- or
      androgen withdrawal-mediated BCRP/ABCG2 transcription in human cancer cells.
AB  - Phosphorylated cyclic-AMP (cAMP) response element binding protein (p-CREB) is a
      downstream effector of a variety of important signaling pathways. We investigated
      whether the human BCRP promoter contains a functional cAMP response element
      (CRE). 8Br-cAMP, a cAMP analogue, increased the activity of a BCRP promoter
      reporter construct and BCRP mRNA in human carcinoma cells. Epidermal growth
      factor receptor (EGFR) pathway activation also led to an increase in p-CREB and
      in BCRP promoter reporter activity via two major downstream EGFR signaling
      pathways: the phosphotidylinositol-3-kinase (PI3K)/AKT pathway and the mitogen
      activated protein kinase (MAPK) pathway. EGF treatment increased the
      phosphorylation of EGFR, AKT, ERK and CREB, while simultaneously enhancing BCRP
      mRNA and functional protein expression. EGF-stimulated CREB phosphorylation and
      BCRP induction were diminished by inhibition of EGFR, PI3K/AKT or RAS/MAPK
      signaling. CREB silencing using RNA interference reduced basal levels of BCRP
      mRNA and diminished the induction of BCRP by EGF. Chromatin immunoprecipitation
      assays confirmed that a putative CRE site on the BCRP promoter bound p-CREB by a
      point mutation of the CRE site abolished EGF-induced stimulation of BCRP promoter
      reporter activity. Furthermore, the CREB co-activator, cAMP-regulated
      transcriptional co-activator (CRTC2), is involved in CREB-mediated BCRP
      transcription: androgen depletion of LNCaP human prostate cancer cells increased
      both CREB phosphorylation and CRTC2 nuclear translocation, and enhanced BCRP
      expression. Silencing CREB or CRTC2 reduced basal BCRP expression and BCRP
      induction under androgen-depletion conditions. This novel CRE site plays a
      central role in mediating BCRP gene expression in several human cancer cell lines
      following activation of multiple cancer-relevant signaling pathways. 

PMID- 25615819
TI  - Health literacy and medication administration performance by caregivers of adults
      with developmental disabilities.
AB  - OBJECTIVES: To measure health literacy (HL) of caregivers of adults with
      intellectual/developmental disabilities (IDDs); to determine the association
      between HL and a medication administration task (MAT) assessment; and to identify
      caregiver characteristics associated with higher HL and MAT scores. DESIGN: Cross
      sectional study. SETTING: Southeastern Michigan. PARTICIPANTS: Caregivers, aged
      18 years or older, who provided supportive care of adults with IDDs.
      INTERVENTIONS: Survey and demonstration. MAIN OUTCOME MEASURES: Short Test of
      Functional Health Literacy in Adults (STOFHLA); a MAT assessment consisting of
      interpretation of five sets of medication instructions followed by demonstration
      of understanding using a pill box; and a survey of caregivers' demographics,
      medication-related experiences, education, characteristics of persons for whom
      they provide care, and care-related activities performed. RESULTS: A total of 47
      caregivers provided data. Caregivers had a mean age of 45.7 +/- 14.6 years; 41
      (87.2%) were women and 38 (80.9%) had education beyond high school. Caregivers
      were involved in obtaining medication from pharmacies, reminded the person with
      IDD to take medications and/or administered them to the person, documented
      medication and health information, and accompanied persons with IDD to physician
      offices. Most did not conduct monitoring procedures. The STOFHLA mean score was
      34.5 +/- 2.5 (median, 35; range, 22-36), while the MAT mean score was 12.0 +/-
      2.2 (median, 12; range, 6-15). Compared with family caregivers, direct support
      staff more frequently had undergone some medication training and had other people
      with whom they could discuss medication questions, but they had worked with the
      person with IDD a significantly shorter amount of time. No significant
      differences in STOFHLA and MAT scores between the family caregivers and direct
      support staff were observed. Caregiver education was significantly correlated
      with the STOFHLA score. MAT scores were not significantly correlated with
      caregiver characteristics. CONCLUSION: Caregivers are involved in the medication
      use process for people who have IDD. Ensuring caregiver understanding of
      medication regimens and/or improving medication-related HL may be an important
      step to ensure safe and effective use of medications by people with IDD.

PMID- 25615820
TI  - Long-lived species have improved proteostasis compared to phylogenetically
      related shorter-lived species.
AB  - Our previous studies have shown that the liver from Naked Mole Rats (NMRs), a
      long-lived rodent, has increased proteasome activity and lower levels of protein
      ubiquitination compared to mice. This suggests that protein quality control might
      play a role in assuring species longevity. To determine whether enhanced
      proteostasis is a common mechanism in the evolution of other long-lived species,
      here we evaluated the major players in protein quality control including
      autophagy, proteasome activity, and heat shock proteins (HSPs), using skin
      fibroblasts from three phylogenetically-distinct pairs of short- and long-lived
      mammals: rodents, marsupials, and bats. Our results indicate that in all cases,
      macroautophagy was significantly enhanced in the longer-lived species, both at
      basal level and after induction by serum starvation. Similarly, basal levels of
      most HSPs were elevated in all the longer-lived species. Proteasome activity was
      found to be increased in the long-lived rodent and marsupial but not in bats.
      These observations suggest that long-lived species may have superior mechanisms
      to ensure protein quality, and support the idea that protein homeostasis might
      play an important role in promoting longevity.

PMID- 25615821
TI  - Isolation of a metastable intermediate in a heterometallic Cu(II)-Hg(II) 1D
      polymeric chain: synthesis, crystal structure, and photophysical properties.
AB  - A metastable heterometallic intermediate, [Cu2(bpy)2(DIPSA)2Hg2(OAc)4(DIPSA)2]n
      (1, where OAc = CH3COO(-), bpy = bipyridine, and DIPSA = diisopropylsalicylic
      acid), has been isolated and characterized during the synthesis of 1D polymer
      [Cu2(bpy)2(DIPSA)2(CH3CN)2Hg2(OAc)2(DIPSA)4]n (2) at ambient temperature in
      acetonitrile. Moreover, recrystallization of 2 in methanol results in monomeric
      [Cu(DIPSA)(bpy)(CH3OH)].CH3OH (3). Complexes 1-3 have been characterized by
      elemental analysis, Fourier transform infrared, and UV-vis spectroscopy as well
      as by their single-crystal X-ray structures. The photophysical study suggests the
      quenching of fluorescence of DIPSA upon complexation. 

PMID- 25615822
TI  - Isolation of notoamide S and enantiomeric 6-epi-stephacidin A from the fungus
      Aspergillus amoenus: biogenetic implications.
AB  - Notoamide S has been hypothesized to be a key biosynthetic intermediate for
      characteristic metabolites stephacidin A, notoamide B, and versicolamide B in
      Aspergillus sp. but has not yet been isolated. The isolation of notoamide S and
      an enantiomeric mixture of 6-epi-stephacidin A enriched with the (-)-isomer from
      Aspergillus amoenus is reported. The presence of (+)-versicolamide B suggests
      that the fungus possesses only the oxidase, which converts (+)-6-epi-stephacidin
      A into (+)-Versicolamide B, but not for (-)-6-epi-Stephacidin A. 

PMID- 25615823
TI  - Fish intake and risk of liver cancer: a meta-analysis.
AB  - BACKGROUND: Increasing laboratory findings indicate that n-3 fatty acids, mainly
      derived from fish, inhibit cancer development and progression, but results from
      epidemiologic studies have been inconsistent and inconclusive. OBJECTIVE: To
      evaluate the association of fish intake with risk of liver cancer by conducting a
      meta-analysis. METHODS: Published case-control/cohort studies that evaluated the
      relationship between total fish intake and risk of liver cancer were found on
      PubMed and EMBASE. The pooled relative risks (RRs) with 95% confidence intervals
      (CIs) were obtained with the random-effects model. RESULTS: Five retrospective
      case-control studies and 5 prospective cohort studies were included in the final
      analysis, involving a total of 3 624 liver cancer cases. Comparing the highest
      with the lowest category of total fish intake, the pooled RRs of liver cancer
      were 0.79 (95% CI, 0.59-1.06) for case-control studies, 0.82 (95% CI, 0.70-0.96)
      for cohort studies and 0.82 (95% CI, 0.71-0.94) for all studies combined. The
      protective effects of total fish intake against liver cancer were confirmed by
      stratified and sensitivity analyses. In addition, an increase in fish intake of 1
      serving/week was estimated to be significantly associated with 6% lower risk of
      liver cancer (RR = 0.94, 95% CI, 0.91-0.98). CONCLUSIONS: Findings from this meta
      analysis suggest that a higher fish intake is associated with reduced risk of
      liver cancer.

PMID- 25615824
TI  - Regulation of oncogene expression in T-DNA-transformed host plant cells.
AB  - Virulent Agrobacterium tumefaciens strains integrate their T-DNA into the plant
      genome where the encoded agrobacterial oncogenes are expressed and cause crown
      gall disease. Essential for crown gall development are IaaH (indole-3-acetamide
      hydrolase), IaaM (tryptophan monooxygenase) and Ipt (isopentenyl transferase),
      which encode enzymes for the biosynthesis of auxin (IaaH, IaaM) and cytokinin
      (Ipt). Although these oncogenes are well studied as the tumor-inducing principle,
      nothing is known about the regulation of oncogene expression in plant cells. Our
      studies show that the intergenic regions (IGRs) between the coding sequences
      (CDS) of the three oncogenes function as promoters in plant cells. These
      promoters possess a eukaryotic sequence organization and cis-regulatory elements
      for the binding of plant transcription factors. WRKY18, WRKY40, WRKY60 and ARF5
      were identified as activators of the Ipt promoter whereas IaaH and IaaM is
      constitutively expressed and no transcription factor further activates their
      promoters. Consistent with these results, the wrky triple mutant plants in
      particular, develops smaller crown galls than wild-type and exhibits a reduced
      Ipt transcription, despite the presence of an intact ARF5 gene. WRKY40 and WRKY60
      gene expression is induced by A. tumefaciens within a few hours whereas the ARF5
      gene is transcribed later during crown gall development. The WRKY proteins
      interact with ARF5 in the plant nucleus, but only WRKY40 together with ARF5
      synergistically boosts the activation of the Ipt promoter in an auxin-dependent
      manner. From our data, we propose that A. tumefaciens initially induces WRKY40
      gene expression as a pathogen defense response of the host cell. The WRKY protein
      is recruited to induce Ipt expression, which initiates cytokinin-dependent host
      cell division. With increasing auxin levels triggered by ubiquitous expression of
      IaaH and IaaM, ARF5 is activated and interacts with WRKY40 to potentiate Ipt
      expression and balance cytokinin and auxin levels for further cell proliferation.

PMID- 25615825
TI  - Six amino acid residues in a 1200 A2 interface mediate binding of factor VIII to
      an IgG4kappa inhibitory antibody.
AB  - The development of neutralizing anti-factor VIII (FVIII) antibodies complicates
      the treatment of many hemophilia A patients. The C-terminal C2 domain is a
      particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2
      bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which
      recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to
      bind von Willebrand factor (VWF) and phospholipids, revealed that 15 amino acids
      in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each
      with a surface-exposed side chain mutated to alanine or another residue, were
      generated, and surface plasmon resonance studies were carried out to evaluate
      effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic
      analysis of experiments carried out at three temperatures indicated that one beta
      hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and
      F2200) plus two non-contiguous arginines (FVIII-R2215 and R2220), contributed
      appreciably to the affinity. B-domain-deleted (BDD) FVIII-F2196A, FVIII-F2196K
      and FVIII-M2199A were generated and characterized. Their pro-coagulant activities
      and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K
      avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study
      suggests specific sites for amino acid substitutions to rationally design FVIII
      variants capable of evading immunodominant neutralizing anti-FVIII antibodies. 

PMID- 25615827
TI  - Highly efficient quantum dot-sensitized TiO2 solar cells based on multilayered
      semiconductors (ZnSe/CdS/CdSe).
AB  - A new approach by inserting a layer of ZnSe QDs was studied to enhance the
      adsorption of CdS/CdSe QDs resulting in much improved power conversion
      efficiency. ZnSe, CdS and CdSe QDs were sequentially assembled on a
      nanocrystalline TiO2 film to prepare a ZnSe/CdS/CdSe sensitized photoelectrode
      for QD-sensitized solar cell (QDSSC) applications. The results show that the
      performance of QDSSCs is strongly dependent on the order of the QDs with respect
      to TiO2. The pre-assembled ZnSe QD layer acts as a seed layer in the subsequent
      SILAR process, inducing both the nucleation and growth of CdS QDs, whereas CdS
      and CdSe QDs have a complementary effect in light harvesting. In the cascade
      structure of TiO2/ZnSe/CdS/CdSe electrode, a high efficiency of 4.94% and a long
      electron lifetime of 87.4 ms were achieved, which can be attributed to the
      following factors: the higher intensity and red shift of light absorption in 400
      700 nm range increase the electron concentration in TiO2 substrate sensitized by
      ZnSe/CdS/CdSe compared to the others, which directly accelerate electron
      transport in TiO2 and their transfer to FTO glass; the re-organization of energy
      levels among ZnSe, CdS and CdSe forms a stepwise structure of band-edge levels,
      which is advantageous to the electron injection and hole recovery of QDs. 

PMID- 25615826
TI  - Beneficial effects of canagliflozin in combination with pioglitazone on insulin
      sensitivity in rodent models of obese type 2 diabetes.
AB  - BACKGROUND: Despite its insulin sensitizing effects, pioglitazone may induce
      weight gain leading to an increased risk of development of insulin resistance. A
      novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides
      not only glycemic control but also body weight reduction through an insulin
      independent mechanism. The aim of this study was to investigate the combined
      effects of these agents on body weight control and insulin sensitivity. METHODS:
      Effects of combination therapy with canagliflozin and pioglitazone were evaluated
      in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF)
      rats. RESULTS: In the KK-Ay mice, the combination therapy further improved
      glycemic control compared with canagliflozin or pioglitazone monotherapy.
      Furthermore, the combination significantly attenuated body weight and fat gain
      induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early
      intervention with pioglitazone monotherapy almost completely prevented the
      progressive development of hyperglycemia, and no further improvement was observed
      by add-on treatment with canagliflozin. However, the combination significantly
      reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda
      index, suggesting improved whole-body insulin sensitivity. CONCLUSIONS: Our study
      indicates that combination therapy with canagliflozin and pioglitazone improves
      insulin sensitivity partly by preventing glucotoxicity and, at least partly, by
      attenuating pioglitazone-induced body weight gain in two different obese diabetic
      animal models. This combination therapy may prove to be a valuable option for the
      treatment and prevention of obese type 2 diabetes.

PMID- 25615829
TI  - Confidentiality and qualitative research.

PMID- 25615830
TI  - Nutritional considerations for the palliative care patient.
AB  - Many palliative care patients experience nutritional problems as their conditions
      progress. This includes those with progressive neurological conditions, chronic
      obstructive pulmonary disease (COPD) as well as advanced cancer. Nutritional
      issues not only impact patients physically but also psychologically and can also
      have an effect on those caring for them. It is important that patients are
      screened appropriately and that one identifies what symptoms are potentially
      affecting their intake. Decisions should always be patient-centred. Nutritional
      interventions range from food modification and nutritional supplements, to more
      intense methods such as enteral or parenteral nutrition, and these may have
      ethical and legal considerations. This article explores the nutritional issues
      faced by palliative patients, the ethical issues supporting decision-making and
      the methods of nutritional support available. 

PMID- 25615828
TI  - Thymus medulla fosters generation of natural Treg cells, invariant gammadelta T
      cells, and invariant NKT cells: what we learn from intrathymic migration.
AB  - The organization of the thymus into distinct cortical and medullary regions
      enables it to control the step-wise migration and development of immature T-cell
      precursors. Such a process provides access to specialized cortical and medullary
      thymic epithelial cells at defined stages of maturation, ensuring the generation
      of self-tolerant and MHC-restricted conventional CD4(+) and CD8(+) alphabeta T
      cells. The migratory cues and stromal cell requirements that regulate the
      development of conventional alphabeta T cells have been well studied. However,
      the thymus also fosters the generation of several immunoregulatory T-cell
      populations that form key components of both innate and adaptive immune
      responses. These include Foxp3(+) natural regulatory T cells, invariant
      gammadelta T cells, and CD1d-restricted invariant natural killer T cells (iNKT
      cells). While less is known about the intrathymic requirements of these
      nonconventional T cells, recent studies have highlighted the importance of the
      thymus medulla in their development. Here, we review recent findings on the
      mechanisms controlling the intrathymic migration of distinct T-cell subsets, and
      relate this to knowledge of the microenvironmental requirements of these cells. 

PMID- 25615831
TI  - Multidisciplinary approaches to moving and handling for formal and informal
      carers in community palliative care.
AB  - Health professionals such as nurses, physiotherapists and occupational therapists
      provide a wealth of support in the community to patients and their carers
      receiving palliative care. Moving and handling is one such support that needs
      careful consideration and assessment including risk, by appropriately qualified
      professionals. A combination of skills are required as well as knowledge of up to
      date equipment to assist the health professional in deciding how to formulate
      safe moving and handling interventions in a timely way. Patients with palliative
      care needs and their carers should be given the appropriate care and support
      necessary using a holistic, flexible and patient-centred approach to service
      delivery. 

PMID- 25615832
TI  - Perspectives of Asians living in Texas on pain management in the last days of
      life.
AB  - AIM: The recognition that someone's ethnic identity does not necessarily predict
      their health-care beliefs and preferences, and lack of scientific evidence on
      this topic provide the fundamental justification for this study. The aim of this
      descriptive qualitative study was to determine the attitudes about and
      preferences for pain management in the last days of life for persons born in
      Japan, China and Vietnam living in Texas. METHOD: Personal interviews were
      conducted to elicit people's perspectives on pain management, such as open or
      indirect acknowledgement of pain and endurance of pain for clarity of
      consciousness. RESULTS: Thematic analysis revealed three overarching themes for
      the Japanese group and five themes each for the Chinese and Vietnamese groups.
      Avoidance of stereotyping based on cultural background was a major finding of
      this study. CONCLUSION: Promoting quality of life in the last days of life is a
      priority for health professionals, and effective, individualised management of
      pain is of the utmost importance.

PMID- 25615833
TI  - Views and experiences of nurses and health-care assistants in nursing care homes
      about the Gold Standards Framework.
AB  - AIM: To explore the views and experiences of nurses and health-care support staff
      about the use of the Gold Standards Framework (GSF) for end-of-life care (EoLC)
      for older people in nursing care homes (NCHs) with GSF accreditation. METHODS: A
      qualitative descriptive study was conducted with three purposively selected NCHs
      in London. Individual interviews were conducted with NCH managers (n=3) and in
      each NCH, a focus group was conducted with registered nurses (RNs) and health
      care assistants (HCAs): focus group 1, n=2 RN, n=2 HCA; focus group 2, n=2 RN,
      n=3 HCA; focus group 3, n=3 RN, n=3 HCA. Interviews were audio-recorded,
      transcribed and analysed using framework analysis. FINDINGS: Three core themes
      were identified: (i) a positive regard for the GSF for care homes (GSFCH); (ii)
      challenges around EoLC for older people; and (iii) difficulties in using the
      GSFCH. CONCLUSIONS: RNs, HCAs and managers regarded the training and support
      afforded by the GSFCH programme to inform EoLC for older residents positively.
      The framework has the potential to promote a coordinated approach to EoLC for
      older people. In the post accreditation period, there is a need for ongoing
      support and development to help embed the key tenets of the GSFCH in the culture
      of caring.

PMID- 25615834
TI  - Nurses' attitudes towards euthanasia: a cross-sectional study in Iran.
AB  - AIM: Nurses have an important role in caring for terminally ill patients. They
      are often confronted with euthanasia but little is known about their attitudes
      towards it. The present study aimed to examine Iranian Muslim nurses' attitudes
      towards euthanasia. METHODS: In this exploratory cross-sectional study, all
      qualified registered nurses working in two teaching hospitals (Kashani and Hajar
      hospitals) in Iran were invited to participate. The Euthanasia Attitude Scale
      (EAS) was used to assess the nurses' attitude towards euthanasia. Of 266 nurses
      who fit the criteria, 190 participated in the study (response rate 72.9%); 91.1%
      (n=173) were female and 8.9% (n=17) were male. RESULTS: In total, 57.4%, 3.2% and
      39.5% of nurses reported a negative, neutral and positive attitude to euthanasia
      respectively. Nurses reported their most negative attitude to the domain
      'practical consideration' with mean of 2.36+/-0.9 and most positive attitude to
      the domain 'treasuring life' with a mean EAS score of 2.85+/-0.4. CONCLUSION: The
      majority of Muslim nurses were found to have negative attitudes to euthanasia. We
      recommend that future studies should be conducted to examine Muslim nurses'
      attitudes to euthanasia in different cultures to determine the role of culture
      and religious beliefs in attitude to euthanasia.

PMID- 25615836
TI  - A rapid amplification/detection assay for analysis of Mycobacterium tuberculosis
      using an isothermal and silicon bio-photonic sensor complex.
AB  - Global tuberculosis (TB) control is hampered by cost and slow or insensitive
      diagnostic methods to be used for TB diagnosis in clinic. Thus, TB still remains
      a major global health problem. The failure to rapidly and accurately diagnose of
      TB has posed significant challenges with consequent secondary resistance and
      ongoing transmission. We developed a rapid Mycobacterium tuberculosis (MTB)
      amplification/detection method, called MTB isothermal solid-phase
      amplification/detection (MTB-ISAD), that couples isothermal solid-phase
      amplification and a silicon biophotonics-based detection sensor to allow the
      simultaneous amplification and detection of MTB in a label-free and real-time
      manner. We validated the clinical utility of the MTB-ISAD assay by detecting MTB
      nucleic acid in sputum samples from 42 patients. We showed the ability of the MTB
      ISAD assay to detect MTB in 42 clinical specimens, confirming that the MTB-ISAD
      assay is fast (<20 min), highly sensitive, accurate (>90%, 38/42), and cost
      effective because it is a label-free method and does not involve thermal cycling.
      The MTB-ISAD assay has improved time-efficiency, affordability, and sensitivity
      compared with many existing methods. Therefore, it is potentially adaptable for
      better diagnosis across various clinical applications.

PMID- 25615838
TI  - Cup-like blasts in acute myeloid leukemia.
AB  - A patient with AML with normal karyotype and the cytological pattern of cup-like
      blasts (CLB) is reported. The typical morphology on Pappenheim stained blood
      smears is shown. In addition transmission electron microscopy pictures
      demonstrate impressively the invaginated nuclear pocket compressing the
      chromatin. Cup-like blasts usually do not express CD34. There is a close
      relationship of CLB-AML with the molecular aberrations of NPM1 and/or FLT3-ITD.

PMID- 25615837
TI  - Susceptibility of European red deer (Cervus elaphus elaphus) to alimentary
      challenge with bovine spongiform encephalopathy.
AB  - European red deer (Cervus elaphus elaphus) are susceptible to the agent of bovine
      spongiform encephalopathy, one of the transmissible spongiform encephalopathies,
      when challenged intracerebrally but their susceptibility to alimentary challenge,
      the presumed natural route of transmission, is unknown. To determine this,
      eighteen deer were challenged via stomach tube with a large dose of the bovine
      spongiform encephalopathy agent and clinical signs, gross and histological
      lesions, presence and distribution of abnormal prion protein and the attack rate
      recorded. Only a single animal developed clinical disease, and this was acute
      with both neurological and respiratory signs, at 1726 days post challenge
      although there was significant (27.6%) weight loss in the preceding 141 days. The
      clinically affected animal had histological lesions of vacuolation in the
      neuronal perikaryon and neuropil, typical of transmissible spongiform
      encephalopathies. Abnormal prion protein, the diagnostic marker of transmissible
      encephalopathies, was primarily restricted to the central and peripheral nervous
      systems although a very small amount was present in tingible body macrophages in
      the lymphoid patches of the caecum and colon. Serial protein misfolding cyclical
      amplification, an in vitro ultra-sensitive diagnostic technique, was positive for
      neurological tissue from the single clinically diseased deer. All other
      alimentary challenged deer failed to develop clinical disease and were negative
      for all other investigations. These findings show that transmission of bovine
      spongiform encephalopathy to European red deer via the alimentary route is
      possible but the transmission rate is low. Additionally, when deer carcases are
      subjected to the same regulations that ruminants in Europe with respect to the
      removal of specified offal from the human food chain, the zoonotic risk of bovine
      spongiform encephalopathy, the cause of variant Creutzfeldt-Jakob disease, from
      consumption of venison is probably very low. 

PMID- 25615839
TI  - Aryl hydrocarbon receptors in osteoclast lineage cells are a negative regulator
      of bone mass.
AB  - Aryl hydrocarbon receptors (AhRs) play a critical role in various pathological
      and physiological processes. Although recent research has identified AhRs as a
      key contributor to bone metabolism following studies in systemic AhR knockout
      (KO) or transgenic mice, the cellular and molecular mechanism(s) in this process
      remain unclear. In this study, we explored the function of AhR in bone metabolism
      using AhR(RANKDeltaOc/DeltaOc) (RANK(Cre/+);AhR(flox/flox)) mice. We observed
      enhanced bone mass together with decreased resorption in both male and female 12
      and 24-week-old AhR(RANKDeltaOc/DeltaOc) mice. Control mice treated with 3
      methylcholanthrene (3MC), an AhR agonist, exhibited decreased bone mass and
      increased bone resorption, whereas AhR(CtskDeltaOc/DeltaOc)
      (Ctsk(Cre/+);AhR(flox/flox)) mice injected with 3MC appeared to have a normal
      bone phenotype. In vitro, bone marrow-derived macrophages (BMDMs) from
      AhR(RANKDeltaOc/DeltaOc) mice exhibited impaired osteoclastogenesis and repressed
      differentiation with downregulated expression of B lymphocyte-induced maturation
      protein 1 (Blimp1), and cytochrome P450 genes Cyp1b1 and Cyp1a2. Collectively,
      our results not only demonstrated that AhR in osteoclast lineage cells is a
      physiologically relevant regulator of bone resorption, but also highlighted the
      need for further studies on the skeletal actions of AhR inhibitors in osteoclast
      lineage cells commonly associated with bone diseases, especially diseases linked
      to environmental pollutants known to induce bone loss.

PMID- 25615840
TI  - Altered white matter in early visual pathways of humans with amblyopia.
AB  - Amblyopia is a visual disorder caused by poorly coordinated binocular input
      during development. Little is known about the impact of amblyopia on the white
      matter within the visual system. We studied the properties of six major visual
      white-matter pathways in a group of adults with amblyopia (n=10) and matched
      controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography.
      While we did not find significant differences in diffusion properties in cortico
      cortical pathways, patients with amblyopia exhibited increased mean diffusivity
      in thalamo-cortical visual pathways. These findings suggest that amblyopia may
      systematically alter the white matter properties of early visual pathways. 

PMID- 25615841
TI  - Analyzing multitarget activity landscapes using protein-ligand interaction
      fingerprints: interaction cliffs.
AB  - Activity landscape modeling is mostly a descriptive technique that allows
      rationalizing continuous and discontinuous SARs. Nevertheless, the interpretation
      of some landscape features, especially of activity cliffs, is not
      straightforward. As the nature of activity cliffs depends on the ligand and the
      target, information regarding both should be included in the analysis. A specific
      way to include this information is using protein-ligand interaction fingerprints
      (IFPs). In this paper we report the activity landscape modeling of 507 ligand
      kinase complexes (from the KLIFS database) including IFP, which facilitates the
      analysis and interpretation of activity cliffs. Here we introduce the structure
      activity-interaction similarity (SAIS) maps that incorporate information on
      ligand-target contact similarity. We also introduce the concept of interaction
      cliffs defined as ligand-target complexes with high structural and interaction
      similarity but have a large potency difference of the ligands. Moreover, the
      information retrieved regarding the specific interaction allowed the
      identification of activity cliff hot spots, which help to rationalize activity
      cliffs from the target point of view. In general, the information provided by
      IFPs provides a structure-based understanding of some activity landscape
      features. This paper shows examples of analyses that can be carried out when IFPs
      are added to the activity landscape model. 

PMID- 25615842
TI  - The menstrual bleeding questionnaire: development and validation of a
      comprehensive patient-reported outcome instrument for heavy menstrual bleeding.
AB  - OBJECTIVE: To develop and validate a patient-reported outcome measure for women
      with heavy menstrual bleeding (HMB). STUDY DESIGN: Prospective cohort and cross
      sectional studies. SETTING: Outpatient women's health facility. POPULATION: Women
      aged between 18 and 55 years with and without self-reported HMB. METHODS: Using
      data from patients and clinicians, we developed a patient-reported outcome
      measure for HMB; the Menstrual Bleeding Questionnaire (MBQ). Participants in the
      validation studies completed demographic and general health questionnaires and
      either (1) bleeding and quality of life data collected daily on handheld
      computers and the MBQ after 1 month or (2) the MBQ at enrolment only. A subset of
      women also completed the Short-form-36 (SF-36) generic quality of life
      questionnaire. We performed psychometric analyses of the MBQ to assess its
      internal consistency as well as its content and concurrent validity and ability
      to discriminate between women with and without HMB. MAIN OUTCOME MEASURES:
      Psychometric properties of the questionnaire. RESULTS: Overall, 182 women
      participated in the MBQ validation studies. We found that the MBQ domains were
      internally consistent (Cronbach's alpha = 0.87-0.94). There was excellent
      correlation between daily bleeding-related symptom data and the MBQ completed at
      1 month (rho > 0.7 for all domains). We found low to moderate correlation between
      the MBQ scores and SF-36 scores (rho = -0.15 to -0.45). The MBQ clearly
      discriminated between women with and without HMB (mean MBQ score = 10.6 versus
      30.8, P < 0.0001). CONCLUSIONS: The MBQ is a valid patient-reported outcome
      measure for HMB that has the potential to improve the evaluation of women with
      self-reported HMB in research and clinical practice.

PMID- 25615843
TI  - Pneumococcal vaccination reduced the risk of acute otitis media: Cohort study.
AB  - BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to
      Japan in 2009, and after that invasive pneumococcal disease has gradually
      decreased. There are few data, however, on the effectiveness of PCV7 against
      acute otitis media (AOM) in Japan. METHODS: From 10 daycare centers in Sapporo,
      Japan, 614 parents participated in the survey. Each parent reported whether their
      child subject had received one or more doses of PCV7, and, if so, the exact dates
      of receiving PCV7 were verified by reviewing their maternal and child health
      handbooks marked by a pediatrician. AOM was diagnosed by otorhinolaryngologist or
      pediatrician. Cox's proportional hazard model was used for calculating the hazard
      ratio (HR) of AOM incidence reduced by PCV7 inoculation. RESULTS: Inoculation of
      PCV7 significantly reduced the risk of AOM (crude HR, 0.63; 95%CI: 0.50-0.79).
      Adjusting for potentially confounding variables reduced the risk further
      (adjusted HR, 0.32; 95%CI: 0.23-0.44). On stratification by subject age on 30
      April 2012, PCV7 was significantly associated with a reduced risk of AOM in both
      infants < 3 years old, and in children >= 3 years. CONCLUSION: PCV7 is
      effectiveness in reducing the risk of AOM both in infants < 3 years old, and in
      young children >= 3 years in Japan.

PMID- 25615844
TI  - A population-based cohort study of 394,401 children followed for 10 years
      exhibits sustained effectiveness of scoliosis screening.
AB  - BACKGROUND CONTEXT: The value of scoliosis screening has been recently shown in a
      multicenter randomized controlled trial. However, the long-term sustainability of
      the clinical effectiveness of scoliosis screening as a routine health service
      remains unknown. PURPOSE: The aim of this study was to assess the sustainability
      of the clinical effectiveness of school scoliosis screening. STUDY
      DESIGN/SETTING: A large population-based cohort study with a 10-year follow-up
      was conducted. PATIENT SAMPLE: A total of 394,401 students who were in the fifth
      grade during the five academic years from 1995/1996 to 1999/2000 formed five
      consecutive annual cohorts. The students were eligible for the Hong Kong
      scoliosis screening program, with their screening history and medical records
      until their nineteenth birthdays being assessed. OUTCOME MEASURES: The outcome
      measures considered in the study were development of adolescent idiopathic
      scoliosis by the 19 years of age and the Cobb angle. METHODS: The clinical
      effectiveness of scoliosis screening was assessed by referral rate for
      radiographic diagnosis, sensitivity, specificity, and predictive values. RESULTS:
      A total of 306,144 students (78%) participated in scoliosis screening, which used
      a two-tier system. The prevalence of curves of 20 degrees  or greater was 1.8%
      (95% confidence interval [CI], 1.7-1.8%), whereas the referral rate for
      radiography, the sensitivity, and the positive predictive value (PPV) for curves
      of 20 degrees  or greater were 4.1% (95% CI, 4.0-4.2%), 91% (95% CI, 90-92%), and
      40% (95% CI, 39-41%), respectively. Across the five consecutive annual cohorts,
      the prevalence and sensitivity for curves of 20 degrees  or greater increased by
      0.23% (95% CI, 0.21-0.25%; p<.001) and 0.76% (95% CI, 0.43-1.04%; p<.001) per
      year, respectively; however, the PPV was reduced by 1.71% (95% CI, 1.09-2.33%;
      p<.001) per year. CONCLUSIONS: This report describes the first large population
      based study with a long-term follow-up indicating that a scoliosis screening
      program can have sustained clinical effectiveness in identifying patients with
      adolescent idiopathic scoliosis needing clinical observation. As the prevalence
      of adolescent idiopathic scoliosis increases, scoliosis screening should be
      continued as a routine health service in schools or by general practitioners if
      there is no scoliosis screening policy.

PMID- 25615846
TI  - Preoperative predictors of increased hospital costs in elective anterior cervical
      fusions: a single-institution analysis of 1,082 patients.
AB  - BACKGROUND CONTEXT: The frequency of anterior cervical fusion (ACF) surgery and
      total hospital costs in spine surgery have substantially increased in the last
      several years. PURPOSE: To determine which patient comorbidities are associated
      with increased total hospital costs after elective one- or two-level ACFs. STUDY
      DESIGN/SETTING: Retrospective cohort analysis. PATIENT SAMPLE: Individuals who
      have undergone elective one- or two-level ACFs at our single institution. The
      total number of patients amounted to 1,082. OUTCOME MEASURES: Total hospital
      costs during single admission. METHODS: Multivariate linear regression models
      were used to analyze independent effects of preoperative patient characteristics
      on total hospital costs. Univariate analysis was used to examine association of
      these characteristics on operative time, length of hospital stay (LOS), and
      complications. RESULTS: Age, obesity, and diabetes were independently associated
      with increased average hospital costs of $1,404 (95% confidence interval [CI],
      $857-$1,951; p<.001), $681 (95% CI, $285-$1,076; p=.001), and $1,877 (95% CI,
      $726-$3,072; p=.001), respectively. Age was associated with increased LOS
      (p<.001) and complications (p<.001) but not operative time (p=.431). Diabetes was
      associated with increased LOS (p<.001) and complications (p=.042) but not
      operative time (p=.234). Obesity was not associated with increased LOS (p=.164),
      complications (p=.890), or operative time (p=.067). CONCLUSIONS: This study
      highlights the patient comorbidities associated with increased hospital costs
      after one- or two-level ACFs and the potential drivers of these costs.

PMID- 25615845
TI  - The clinical importance of sacral slanting in patients with adolescent idiopathic
      scoliosis undergoing surgery.
AB  - BACKGROUND CONTEXT: The phenomenon of sacral slanting has not been assessed in
      patients with adolescent idiopathic scoliosis (AIS). It could be important in
      determining distal fusion level. PURPOSE: The purpose of this study is to clarify
      sacral slanting and to reveal frequency, character, and clinical importance of
      sacral slanting in AIS patients who underwent surgery. STUDY DESIGN/SETTING:
      Retrospective review of radiographs. PATIENT SAMPLE: The study included 389
      patients who underwent surgery for AIS at a single center. OUTCOME MEASURES:
      Slanted angles of sacrum, distal curve types, and postoperative decompensation
      were assessed in whole spine anteroposterior radiographs. METHODS: This was a
      retrospective case series, which included 389 AIS patients who underwent
      corrective surgeries. The degree of sacral slanting was defined as the angle
      between the horizontal line and the upper end plate of the sacrum. Distal curves
      were classified according to the direction of L4 tilt (L4-left type and L4-right
      type). The frequency, direction, and relationship with curve types were analyzed
      descriptively. Postoperative changes of sacral slanting were compared by paired t
      test. Decompensation by distal fusion level and distal curve types was analyzed
      descriptively. The p value of less than .05 was considered as statistically
      significant. RESULTS: The frequency of sacral slanting was 19.5% (76 of 389),
      29.6% (115 of 389), and 40.6% (158 of 389) by using criteria of 5 degrees , 4
      degrees , and 3 degrees , respectively. The 86.7% showed sacral slanting on the
      left side. The combination of L4-left type with left-sided sacral slanting was
      the most frequent (124 of 158, 78.7%). Slanted angles were decreased in some
      cases after surgery. Decompensation in the coronal plane was observed in 2 of 22
      patients (9.1%) with a distal fusion level of L4 but in none of the 70 patients
      with a distal fusion level of L3. CONCLUSIONS: Sacral slanting in patients with
      AIS is a unique and frequently observed finding that has never been researched to
      date. Most importantly, sacral slanting is a critical consideration in selecting
      distal fusion level when planning corrective surgery in patients with AIS.

PMID- 25615847
TI  - Reoperation rates in the surgical treatment of spinal metastases.
AB  - BACKGROUND CONTEXT: The surgical treatment in spinal metastases has been shown to
      improve function and neurologic outcome. Unplanned hospital readmissions can be
      costly and cause unnecessary harm. PURPOSE: Our aim was to first analyze the
      reoperation rate and indications for this revision surgery in spinal metastases
      from an academic tertiary spinal institute and, second, to make comparisons on
      outcome (neurology and survival) against patients who underwent single surgery
      only. STUDY DESIGN/SETTING: This was an ambispective review of all patients
      treated surgically over an 8-year period considering their neurologic and
      survival outcome data. Statistical analysis was performed using IBM SPSS 20.
      Because all scale values did not follow the normal distribution and significant
      outlier values existed, all descriptive statistics and comparisons were made
      using median values and the median test. Crosstabs and Pearson correlation were
      used to calculate differences between percentages and ordinal/nominal values. For
      two population proportions, the z test was used to calculate differences. The log
      rank Mantel-Cox analysis was used to compare survival. PATIENT SAMPLE: During the
      8 years' study period, there were 384 patients who underwent urgent surgery for
      spinal metastasis. Of these, 289 patients were included who had sufficient
      information available. There were 31 reoperations performed (10.7%; mean age, 60
      years; 13 male, 18 female). Exclusion criteria included patients treated solely
      by radiotherapy, patients who had undergone surgery for spinal metastasis before
      the study period, and those who had other causes for neurologic dysfunction such
      as stroke. OUTCOME MEASURES: The outcomes considered in this study were revised
      Tokuhashi score, preoperative/postoperative Frankel scores, and survival.
      METHODS: We performed an ambispective review of all patients treated surgically
      from our comprehensive database during the study period (October 2004 to October
      2012). We reviewed all patient records on the database, including patient
      demographics and reoperation rates. RESULTS: Reoperations were performed in the
      same admission in the majority of patients (n=20), whereas 11 patients had their
      second procedure in subsequent hospitalization. The reasons for their revision
      surgery were as follows: surgical site infection (SSI; 13 of 31 [42%]), failure
      of instrumentation (9 of 31 [29%]), local recurrence (5 of 31 [16%]), hematoma
      evacuation (2 of 31 [6%]), and others (2 of 31 [6%]).When comparing the "single
      surgery" and "revision surgery" groups, we found that the median preoperative and
      postoperative Frankel scores were similar at Grade 4 (range, 1-5) for both groups
      (preoperative, p=.92; postoperative, p=.87). However, 20 patients (8%) from the
      single surgery group and 7 (23%) from the revision group had a worse
      postoperative score, and this was significantly different (p=.01). No significant
      difference was found (p=.66) in the revised Tokuhashi score. The median number of
      survival days was similar (p=.719)-single surgery group: 250 days (range, 5-2,597
      days) and revision group: 215 days (range, 9-1,352 days). CONCLUSION: There was a
      modest reoperation rate (10.7%) in our patients treated surgically for spinal
      metastases over an 8-year period. Most of these were for SSI (42%), failure of
      instrumentation (26%), and local recurrence (16%). Patients with metastatic
      disease could benefit from revision surgery with comparable median survival rates
      but relatively poorer neurologic outcomes. This study may help to assist with
      informed decision making for this vulnerable patient group.

PMID- 25615848
TI  - Monitoring for idiopathic scoliosis curve progression using surface topography
      asymmetry analysis of the torso in adolescents.
AB  - BACKGROUND CONTEXT: At first visit and each clinical follow-up session, patients
      with adolescent idiopathic scoliosis (AIS) undergo radiographic examination, from
      which the Cobb angle is measured. The cumulative exposure to X-ray radiation
      justifies efforts in developing noninvasive methods for scoliosis monitoring.
      PURPOSE: To determine the capability of the three-dimensional markerless surface
      topography (ST) asymmetry analysis to detect >=5 degrees  progression in the
      spinal curvature in patients with AIS over 1-year follow-up interval. STUDY
      DESIGN/SETTING: Cross-sectional study in a specialized scoliosis clinic. PATIENT
      SAMPLE: In this study, baseline and 1-year follow-up full torso ST scans of 100
      patients with AIS were analyzed using three-dimensional markerless asymmetry
      analysis. OUTCOME MEASURES: Patients with DeltaCobb>=5 degrees  and DeltaCobb<5
      degrees  were categorized into progression and nonprogression groups,
      respectively. METHODS: The ST scan of each full torso was analyzed to calculate
      the best plane of symmetry by minimizing the distances between the torso and its
      reflection about the plane of symmetry. Distance between the torso and its
      reflection was measured and displayed as deviation color maps. The difference of
      ST measurements between two successive acquisitions was used to determine if the
      scoliosis has progressed at least 5 degrees  or not. The classification tree
      technique was implemented using the local deformity of the torso in the thoracic
      thoracolumbar (T-TL) and lumbar (L) regions to categorize curves into progression
      and nonprogression groups. The change in maximum deviation and root mean square
      of the deviations in the torso were the parameters effective in capturing the
      curve progression. Funding for this research is provided by the Scoliosis
      Research Society, and Women and Children's Health Research Institute. RESULTS:
      The classification model detected 85.7% of the progression and 71.6% of the
      nonprogression cases. The resulting false-negative rate of 4% for T-TL curves,
      representing the proportion of undetected progressions, confirmed that the
      technique shows promise to monitor the progression of T-TL scoliosis curves.
      Although 100% L curves with progression were detected using the deviation color
      maps of the torsos, because of the small number of analyzed L curves, further
      research is needed before the efficiency of the method in capturing the L curves
      with progression is confirmed. CONCLUSIONS: Using the developed classification
      tree for the patients analyzed in this study, 43% of nonprogression cases between
      two visits would not have to undergo an X-ray examination.

PMID- 25615849
TI  - Revisiting the streptavidin-biotin binding by using an aptamer and displacement
      isothermal calorimetry titration.
AB  - The association constant of a well-known streptavidin-biotin binding has only
      been inferred from separately measured kinetic parameters. In a single
      experiment, we obtained Ka 1 * 10(12)  M(-1) by using a streptavidin-binding
      aptamer and ligand-displacement isothermal titration calorimetry. This study
      explores the challenges of determining thermodynamic parameters and the derived
      equilibrium binding affinity of tight ligand-receptor binding.

PMID- 25615850
TI  - Long lasting activity of nociceptive muscular afferents facilitates bilateral
      flexion reflex pattern in the feline spinal cord.
AB  - Chronic muscular limb pain requires the adoption of motor patterns distinct from
      the classic ipsilateral flexion, crossed extension and corresponding reciprocal
      inhibitions to acute exteroceptive stimulation. Using selective chemical
      activation of group III/IV afferents in gastrocnemius-soleus (GS) muscles we
      investigated bilaterally their reflex responses conditioned by (a) acute
      'myositis' induced by intramuscular carrageenan; and (b) sub-acute 'myositis'
      induced by infusion of complete Freund's adjuvant (CFA). Reflex transmission was
      detected by monosynaptic testing and c-fos staining used to identify increased
      neuronal activity. In all control experiments with chemical stimulation of group
      III/IV afferents, ipsilateral responses conformed to the flexor reflex pattern.
      However, the expected contralateral facilitation of GS motoneurones occurred in
      fewer than 50% trials while only 9% of trials induced contralateral inhibition of
      flexor posterior-biceps-semitendinosus (PBSt) motoneurones. During carrageenan
      acute myositis contralateral PBSt was transiently facilitated by selective
      activation of group III/IV afferents. During CFA-induced myositis, contralateral
      only inhibition of GS motoneurones occurred instead of any facilitation, while
      bidirectionally a crossed facilitation of PBST dominated. These reflex changes
      were mirrored in an enhanced number of neurones with enhanced c-fos expression.
      Muscle pain, particularly if chronically persistent, requires another behavioural
      response pattern than acute exteroceptive pain. 

PMID- 25615851
TI  - Mutational profiling of second primary lung cancers in patients who have received
      radiation for the treatment of Hodgkin's disease.
AB  - Lung cancer (LC) represents the most common solid tumor in survivors of Hodgkin's
      disease (HD), and the assessment of the mutational status of oncogenic driver
      mutations in LC is now standard. We compiled clinical and mutation data (EGFR,
      KRAS, and ALK) from the medical records of patients with LC and a remote history
      of HD. 13 cases of LC following HD were seen, including seven with mutational
      data. Two had EGFR mutations, none had KRAS mutations or ALK translocations. Our
      conclusions are limited by the small sample size, however this report reinforces
      the need to identify driver mutations in lung cancers. 

PMID- 25615852
TI  - Pazopanib and liposomal doxorubicin in the treatment of patients with
      relapsed/refractory epithelial ovarian cancer: a phase Ib study of the Sarah
      Cannon Research Institute.
AB  - PURPOSE: To investigate the combination of liposomal doxorubicin/pazopanib in
      advanced relapsed/refractory ovarian cancer. PATIENTS AND METHODS: Twenty-two
      patients received liposomal doxorubicin/pazopanib. Initial doses (liposomal
      doxorubicin, 40 mg/m2 monthly; pazopanib, 400 mg daily) were too toxic; three
      subsequent groups received lower doses/altered schedules. RESULTS: The maximum
      tolerated doses (MTD) were liposomal doxorubicin, 30 mg/m2, and pazopanib, 400 mg
      daily. Severe toxicity included neutropenia (18%), rash/desquamation (14%),
      hypertension (9%), and hand-foot syndrome (9%). Five of the eight patients
      treated with MTD had grade 3 toxicity during the first two cycles. Dose
      reductions were frequently required. CONCLUSIONS: Further development of the
      liposomal doxorubicin/pazopanib combination is not recommended.

PMID- 25615854
TI  - Two way street - complementary methods.

PMID- 25615853
TI  - Biopsy proven medullary sponge kidney: clinical findings, histopathology, and
      role of osteogenesis in stone and plaque formation.
AB  - Medullary sponge kidney (MSK) is associated with recurrent stone formation, but
      the clinical phenotype is unclear because patients with other disorders may be
      incorrectly labeled MSK. We studied 12 patients with histologic findings
      pathognomonic of MSK. All patients had an endoscopically recognizable pattern of
      papillary malformation, which may be segmental or diffuse. Affected papillae are
      enlarged and billowy, due to markedly enlarged inner medullary collecting ducts
      (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation
      of Bellini ducts, with occasional mineral plugs. Stones may form over white
      (Randall's) plaque, but most renal pelvic stones are not attached, and have a
      similar morphology as ductal stones, which are a mixture of calcium oxalate and
      apatite. Patients had no abnormalities of urinary acidification or acid
      excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria.
      Although both Runx2 and Osterix are expressed in papillae of MSK patients, no
      mineral deposition was seen at the sites of gene expression, arguing against a
      role of these genes in this process. Similar studies in idiopathic calcium stone
      formers showed no expression of these genes at sites of Randall's plaque. The
      most likely mechanism for stone formation in MSK appears to be crystallization
      due to urinary stasis in dilated IMCD with subsequent passage of ductal stones
      into the renal pelvis where they may serve as nuclei for stone formation.

PMID- 25615855
TI  - Combining biophysical methods for the analysis of protein complex stoichiometry
      and affinity in SEDPHAT.
AB  - Reversible macromolecular interactions are ubiquitous in signal transduction
      pathways, often forming dynamic multi-protein complexes with three or more
      components. Multivalent binding and cooperativity in these complexes are often
      key motifs of their biological mechanisms. Traditional solution biophysical
      techniques for characterizing the binding and cooperativity are very limited in
      the number of states that can be resolved. A global multi-method analysis (GMMA)
      approach has recently been introduced that can leverage the strengths and the
      different observables of different techniques to improve the accuracy of the
      resulting binding parameters and to facilitate the study of multi-component
      systems and multi-site interactions. Here, GMMA is described in the software
      SEDPHAT for the analysis of data from isothermal titration calorimetry, surface
      plasmon resonance or other biosensing, analytical ultracentrifugation,
      fluorescence anisotropy and various other spectroscopic and thermodynamic
      techniques. The basic principles of these techniques are reviewed and recent
      advances in view of their particular strengths in the context of GMMA are
      described. Furthermore, a new feature in SEDPHAT is introduced for the simulation
      of multi-method data. In combination with specific statistical tools for GMMA in
      SEDPHAT, simulations can be a valuable step in the experimental design. 

PMID- 25615856
TI  - In crystallo optical spectroscopy (icOS) as a complementary tool on the
      macromolecular crystallography beamlines of the ESRF.
AB  - The analysis of structural data obtained by X-ray crystallography benefits from
      information obtained from complementary techniques, especially as applied to the
      crystals themselves. As a consequence, optical spectroscopies in structural
      biology have become instrumental in assessing the relevance and context of many
      crystallographic results. Since the year 2000, it has been possible to record
      such data adjacent to, or directly on, the Structural Biology Group beamlines of
      the ESRF. A core laboratory featuring various spectrometers, named the Cryobench,
      is now in its third version and houses portable devices that can be directly
      mounted on beamlines. This paper reports the current status of the Cryobench,
      which is now located on the MAD beamline ID29 and is thus called the ID29S
      Cryobench (where S stands for 'spectroscopy'). It also reviews the diverse
      experiments that can be performed at the Cryobench, highlighting the various
      scientific questions that can be addressed. 

PMID- 25615857
TI  - Challenges and solutions for the analysis of in situ, in crystallo micro
      spectrophotometric data.
AB  - Combining macromolecular crystallography with in crystallo micro
      spectrophotometry yields valuable complementary information on the sample,
      including the redox states of metal cofactors, the identification of bound
      ligands and the onset and strength of undesired photochemistry, also known as
      radiation damage. However, the analysis and processing of the resulting data
      differs significantly from the approaches used for solution spectrophotometric
      data. The varying size and shape of the sample, together with the suboptimal
      sample environment, the lack of proper reference signals and the general
      influence of the X-ray beam on the sample have to be considered and carefully
      corrected for. In the present article, how to characterize and treat these sample
      dependent artefacts in a reproducible manner is discussed and the SLS-APE in
      situ, in crystallo optical spectroscopy data-analysis toolbox is demonstrated. 

PMID- 25615858
TI  - Protein-ligand interactions investigated by thermal shift assays (TSA) and dual
      polarization interferometry (DPI).
AB  - Over the last decades, a wide range of biophysical techniques investigating
      protein-ligand interactions have become indispensable tools to complement high
      resolution crystal structure determinations. Current approaches in solution range
      from high-throughput-capable methods such as thermal shift assays (TSA) to highly
      accurate techniques including microscale thermophoresis (MST) and isothermal
      titration calorimetry (ITC) that can provide a full thermodynamic description of
      binding events. Surface-based methods such as surface plasmon resonance (SPR) and
      dual polarization interferometry (DPI) allow real-time measurements and can
      provide kinetic parameters as well as binding constants. DPI provides additional
      spatial information about the binding event. Here, an account is presented of new
      developments and recent applications of TSA and DPI connected to crystallography.

PMID- 25615859
TI  - The accurate assessment of small-angle X-ray scattering data.
AB  - Small-angle X-ray scattering (SAXS) has grown in popularity in recent times with
      the advent of bright synchrotron X-ray sources, powerful computational resources
      and algorithms enabling the calculation of increasingly complex models. However,
      the lack of standardized data-quality metrics presents difficulties for the
      growing user community in accurately assessing the quality of experimental SAXS
      data. Here, a series of metrics to quantitatively describe SAXS data in an
      objective manner using statistical evaluations are defined. These metrics are
      applied to identify the effects of radiation damage, concentration dependence and
      interparticle interactions on SAXS data from a set of 27 previously described
      targets for which high-resolution structures have been determined via X-ray
      crystallography or nuclear magnetic resonance (NMR) spectroscopy. The studies
      show that these metrics are sufficient to characterize SAXS data quality on a
      small sample set with statistical rigor and sensitivity similar to or better than
      manual analysis. The development of data-quality analysis strategies such as
      these initial efforts is needed to enable the accurate and unbiased assessment of
      SAXS data quality. 

PMID- 25615860
TI  - Uniqueness of models from small-angle scattering data: the impact of a hydration
      shell and complementary NMR restraints.
AB  - Small-angle scattering (SAS) has witnessed a breathtaking renaissance and
      expansion over the past 15 years regarding the determination of biomacromolecular
      structures in solution. While important issues such as sample quality, good
      experimental practice and guidelines for data analysis, interpretation,
      presentation, publication and deposition are increasingly being recognized,
      crucial topics such as the uniqueness, precision and accuracy of the structural
      models obtained by SAS are still only poorly understood and addressed. The
      present article provides an overview of recent developments in these fields with
      a focus on the influence of complementary NMR restraints and of a hydration shell
      on the uniqueness of biomacromolecular models. As a first topic, the impact of
      incorporating NMR orientational restraints in addition to SAS distance restraints
      is discussed using a quantitative visual representation that illustrates how the
      possible conformational space of a two-body system is reduced as a function of
      the available data. As a second topic, the impact of a hydration shell on
      modelling parameters of a two-body system is illustrated, in particular on its
      inter-body distance. Finally, practical recommendations are provided to take both
      effects into account and promising future perspectives of SAS approaches are
      discussed. 

PMID- 25615861
TI  - BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high
      throughput X-ray solution scattering experiments.
AB  - Small-angle X-ray scattering (SAXS) of macromolecules in solution is in
      increasing demand by an ever more diverse research community, both academic and
      industrial. To better serve user needs, and to allow automated and high
      throughput operation, a sample changer (BioSAXS Sample Changer) that is able to
      perform unattended measurements of up to several hundred samples per day has been
      developed. The Sample Changer is able to handle and expose sample volumes of down
      to 5 ul with a measurement/cleaning cycle of under 1 min. The samples are stored
      in standard 96-well plates and the data are collected in a vacuum-mounted
      capillary with automated positioning of the solution in the X-ray beam. Fast and
      efficient capillary cleaning avoids cross-contamination and ensures
      reproducibility of the measurements. Independent temperature control for the well
      storage and for the measurement capillary allows the samples to be kept cool
      while still collecting data at physiological temperatures. The Sample Changer has
      been installed at three major third-generation synchrotrons: on the BM29 beamline
      at the European Synchrotron Radiation Facility (ESRF), the P12 beamline at the
      PETRA-III synchrotron (EMBL@PETRA-III) and the I22/B21 beamlines at Diamond Light
      Source, with the latter being the first commercial unit supplied by Bruker ASC. 

PMID- 25615862
TI  - ISPyB for BioSAXS, the gateway to user autonomy in solution scattering
      experiments.
AB  - Logging experiments with the laboratory-information management system ISPyB
      (Information System for Protein crystallography Beamlines) enhances the
      automation of small-angle X-ray scattering of biological macromolecules in
      solution (BioSAXS) experiments. The ISPyB interface provides immediate user
      oriented online feedback and enables data cross-checking and downstream analysis.
      To optimize data quality and completeness, ISPyBB (ISPyB for BioSAXS) makes it
      simple for users to compare the results from new measurements with previous
      acquisitions from the same day or earlier experiments in order to maximize the
      ability to collect all data required in a single synchrotron visit. The graphical
      user interface (GUI) of ISPyBB has been designed to guide users in the
      preparation of an experiment. The input of sample information and the ability to
      outline the experimental aims in advance provides feedback on the number of
      measurements required, calculation of expected sample volumes and time needed to
      collect the data: all of this information aids the users to better prepare for
      their trip to the synchrotron. A prototype version of the ISPyBB database is now
      available at the European Synchrotron Radiation Facility (ESRF) beamline BM29 and
      is already greatly appreciated by academic users and industrial clients. It will
      soon be available at the PETRA III beamline P12 and the Diamond Light Source
      beamlines I22 and B21. 

PMID- 25615863
TI  - Memprot: a program to model the detergent corona around a membrane protein based
      on SEC-SAXS data.
AB  - The application of small-angle X-ray scattering (SAXS) to structural
      investigations of transmembrane proteins in detergent solution has been hampered
      by two main inherent hurdles. On the one hand, the formation of a detergent
      corona around the hydrophobic region of the protein strongly modifies the
      scattering curve of the protein. On the other hand, free micelles of detergent
      without a precisely known concentration coexist with the protein-detergent
      complex in solution, therefore adding an uncontrolled signal. To gain robust
      structural information on such systems from SAXS data, in previous work,
      advantage was taken of the online combination of size-exclusion chromatography
      (SEC) and SAXS, and the detergent corona around aquaporin-0, a membrane protein
      of known structure, could be modelled. A precise geometrical model of the corona,
      shaped as an elliptical torus, was determined. Here, in order to better
      understand the correlations between the corona model parameters and to discuss
      the uniqueness of the model, this work was revisited by analyzing systematic SAXS
      simulations over a wide range of parameters of the torus. 

PMID- 25615864
TI  - Acoustic transfer of protein crystals from agarose pedestals to micromeshes for
      high-throughput screening.
AB  - Acoustic droplet ejection (ADE) is an emerging technology with broad applications
      in serial crystallography such as growing, improving and manipulating protein
      crystals. One application of this technology is to gently transfer crystals onto
      MiTeGen micromeshes with minimal solvent. Once mounted on a micromesh, each
      crystal can be combined with different chemicals such as crystal-improving
      additives or a fragment library. Acoustic crystal mounting is fast (2.33
      transfers s(-1)) and all transfers occur in a sealed environment that is in vapor
      equilibrium with the mother liquor. Here, a system is presented to retain
      crystals near the ejection point and away from the inaccessible dead volume at
      the bottom of the well by placing the crystals on a concave agarose pedestal
      (CAP) with the same chemical composition as the crystal mother liquor. The bowl
      shaped CAP is impenetrable to crystals. Consequently, gravity will gently move
      the crystals into the optimal location for acoustic ejection. It is demonstrated
      that an agarose pedestal of this type is compatible with most commercially
      available crystallization conditions and that protein crystals are readily
      transferred from the agarose pedestal onto micromeshes with no loss in
      diffraction quality. It is also shown that crystals can be grown directly on
      CAPs, which avoids the need to transfer the crystals from the hanging drop to a
      CAP. This technology has been used to combine thermolysin and lysozyme crystals
      with an assortment of anomalously scattering heavy atoms. The results point
      towards a fast nanolitre method for crystal mounting and high-throughput
      screening. 

PMID- 25615865
TI  - Experimental phasing for structure determination using membrane-protein crystals
      grown by the lipid cubic phase method.
AB  - Despite the marked increase in the number of membrane-protein structures solved
      using crystals grown by the lipid cubic phase or in meso method, only ten have
      been determined by SAD/MAD. This is likely to be a consequence of the technical
      difficulties associated with handling proteins and crystals in the sticky and
      viscous hosting mesophase that is usually incubated in glass sandwich plates for
      the purposes of crystallization. Here, a four-year campaign aimed at phasing the
      in meso structure of the integral membrane diacylglycerol kinase (DgkA) from
      Escherichia coli is reported. Heavy-atom labelling of this small hydrophobic
      enzyme was attempted by pre-labelling, co-crystallization, soaking, site-specific
      mercury binding to genetically engineered single-cysteine mutants and
      selenomethionine incorporation. Strategies and techniques for special handling
      are reported, as well as the typical results and the lessons learned for each of
      these approaches. In addition, an assay to assess the accessibility of cysteine
      residues in membrane proteins for mercury labelling is introduced. The various
      techniques and strategies described will provide a valuable reference for future
      experimental phasing of membrane proteins where crystals are grown by the lipid
      cubic phase method. 

PMID- 25615866
TI  - Collaborative computational project for electron cryo-microscopy.
AB  - The Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) has
      recently been established. The aims of the project are threefold: to build a
      coherent cryoEM community which will provide support for individual scientists
      and will act as a focal point for liaising with other communities, to support
      practising scientists in their use of cryoEM software and finally to support
      software developers in producing and disseminating robust and user-friendly
      programs. The project is closely modelled on CCP4 for macromolecular
      crystallography, and areas of common interest such as model fitting, underlying
      software libraries and tools for building program packages are being exploited.
      Nevertheless, cryoEM includes a number of techniques covering a large range of
      resolutions and a distinct project is required. In this article, progress so far
      is reported and future plans are discussed. 

PMID- 25615867
TI  - A national facility for biological cryo-electron microscopy.
AB  - Three-dimensional electron microscopy is an enormously powerful tool for
      structural biologists. It is now able to provide an understanding of the
      molecular machinery of cells, disease processes and the actions of pathogenic
      organisms from atomic detail through to the cellular context. However, cutting
      edge research in this field requires very substantial resources for equipment,
      infrastructure and expertise. Here, a brief overview is provided of the plans for
      a UK national three-dimensional electron-microscopy facility for integrated
      structural biology to enable internationally leading research on the machinery of
      life. State-of-the-art equipment operated with expert support will be provided,
      optimized for both atomic-level single-particle analysis of purified
      macromolecules and complexes and for tomography of cell sections. The access to
      and organization of the facility will be modelled on the highly successful
      macromolecular crystallography (MX) synchrotron beamlines, and will be embedded
      at the Diamond Light Source, facilitating the development of user-friendly
      workflows providing near-real-time experimental feedback. 

PMID- 25615868
TI  - Tools for macromolecular model building and refinement into electron cryo
      microscopy reconstructions.
AB  - The recent rapid development of single-particle electron cryo-microscopy (cryo
      EM) now allows structures to be solved by this method at resolutions close to 3
      A. Here, a number of tools to facilitate the interpretation of EM reconstructions
      with stereochemically reasonable all-atom models are described. The BALBES
      database has been repurposed as a tool for identifying protein folds from density
      maps. Modifications to Coot, including new Jiggle Fit and morphing tools and
      improved handling of nucleic acids, enhance its functionality for interpreting EM
      maps. REFMAC has been modified for optimal fitting of atomic models into EM maps.
      As external structural information can enhance the reliability of the derived
      atomic models, stabilize refinement and reduce overfitting, ProSMART has been
      extended to generate interatomic distance restraints from nucleic acid reference
      structures, and a new tool, LIBG, has been developed to generate nucleic acid
      base-pair and parallel-plane restraints. Furthermore, restraint generation has
      been integrated with visualization and editing in Coot, and these restraints have
      been applied to both real-space refinement in Coot and reciprocal-space
      refinement in REFMAC. 

PMID- 25615869
TI  - Structure calculation, refinement and validation using CcpNmr Analysis.
AB  - CcpNmr Analysis provides a streamlined pipeline for both NMR chemical shift
      assignment and structure determination of biological macromolecules. In addition,
      it encompasses tools to analyse the many additional experiments that make NMR
      such a pivotal technique for research into complex biological questions. This
      report describes how CcpNmr Analysis can seamlessly link together all of the
      tasks in the NMR structure-determination process. It details each of the stages
      from generating NMR restraints [distance, dihedral, hydrogen bonds and residual
      dipolar couplings (RDCs)], exporting these to and subsequently re-importing them
      from structure-calculation software (such as the programs CYANA or ARIA) and
      analysing and validating the results obtained from the structure calculation to,
      ultimately, the streamlined deposition of the completed assignments and the
      refined ensemble of structures into the PDBe repository. Until recently, such
      solution-structure determination by NMR has been quite a laborious task,
      requiring multiple stages and programs. However, with the new enhancements to
      CcpNmr Analysis described here, this process is now much more intuitive and
      efficient and less error-prone. 

PMID- 25615870
TI  - In pursuit of an accurate spatial and temporal model of biomolecules at the
      atomistic level: a perspective on computer simulation.
AB  - Despite huge advances in the computational techniques available for simulating
      biomolecules at the quantum-mechanical, atomistic and coarse-grained levels,
      there is still a widespread perception amongst the experimental community that
      these calculations are highly specialist and are not generally applicable by
      researchers outside the theoretical community. In this article, the successes and
      limitations of biomolecular simulation and the further developments that are
      likely in the near future are discussed. A brief overview is also provided of the
      experimental biophysical methods that are commonly used to probe biomolecular
      structure and dynamics, and the accuracy of the information that can be obtained
      from each is compared with that from modelling. It is concluded that progress
      towards an accurate spatial and temporal model of biomacromolecules requires a
      combination of all of these biophysical techniques, both experimental and
      computational. 

PMID- 25615871
TI  - Mycorrhiza symbiosis increases the surface for sunlight capture in Medicago
      truncatula for better photosynthetic production.
AB  - Arbuscular mycorrhizal (AM) fungi play a prominent role in plant nutrition by
      supplying mineral nutrients, particularly inorganic phosphate (Pi), and also
      constitute an important carbon sink. AM stimulates plant growth and development,
      but the underlying mechanisms are not well understood. In this study, Medicago
      truncatula plants were grown with Rhizophagus irregularis BEG141 inoculum (AM),
      mock inoculum (control) or with P(i) fertilization. We hypothesized that AM
      stimulates plant growth through either modifications of leaf anatomy or
      photosynthetic activity per leaf area. We investigated whether these effects are
      shared with P(i) fertilization, and also assessed the relationship between levels
      of AM colonization and these effects. We found that increased P(i) supply by
      either mycorrhization or fertilization led to improved shoot growth associated
      with increased nitrogen uptake and carbon assimilation. Both mycorrhized and P(i)
      fertilized plants had more and longer branches with larger and thicker leaves
      than the control plants, resulting in an increased photosynthetically active
      area. AM-specific effects were earlier appearance of the first growth axes and
      increased number of chloroplasts per cell section, since they were not induced by
      P(i) fertilization. Photosynthetic activity per leaf area remained the same
      regardless of type of treatment. In conclusion, the increase in growth of
      mycorrhized and P(i)-fertilized Medicago truncatula plants is linked to an
      increase in the surface for sunlight capture, hence increasing their
      photosynthetic production, rather than to an increase in the photosynthetic
      activity per leaf area.

PMID- 25615873
TI  - Green chemistry for nanoparticle synthesis.
AB  - The application of the twelve principles of green chemistry in nanoparticle
      synthesis is a relatively new emerging issue concerning the sustainability. This
      field has received great attention in recent years due to its capability to
      design alternative, safer, energy efficient, and less toxic routes towards
      synthesis. These routes have been associated with the rational utilization of
      various substances in the nanoparticle preparations and synthetic methods, which
      have been broadly discussed in this tutorial review. This article is not meant to
      provide an exhaustive overview of green synthesis of nanoparticles, but to
      present several pivotal aspects of synthesis with environmental concerns,
      involving the selection and evaluation of nontoxic capping and reducing agents,
      the choice of innocuous solvents and the development of energy-efficient
      synthetic methods. 

PMID- 25615872
TI  - Parallel chemical switches underlying pollinator isolation in Asian Mitella.
AB  - Floral scents are among the key signals used by pollinators to navigate to
      specific flowers. Thus, evolutionary changes in scents should have strong impacts
      on plant diversification, although scent-mediated plant speciation through
      pollinator shifts has rarely been demonstrated, despite being likely. To examine
      whether and how scent-mediated plant speciation may have occurred, we
      investigated the Asimitellaria plant lineage using multidisciplinary approaches
      including pollinator observations, chemical analyses of the floral scents,
      electroantennographic analyses and behavioural bioassays with the pollinators. We
      also performed phylogenetically independent contrast analyses of the
      pollinator/floral scent associations. First, we confirmed that the pairs of the
      sympatric, cross-fertile Asimitellaria species in three study sites consistently
      attract different pollinators, namely long-tongued and short-tongued fungus
      gnats. We also found that a stereoisomeric set of floral volatiles, the lilac
      aldehydes, could be responsible for the pollinator specificity. This is because
      the compounds consistently elicited responses in the antennae of the long-tongued
      fungus gnats and had contrasting effects on the two pollinators, that is
      triggering the nectaring behaviour of long-tongued fungus gnats while repelling
      short-tongued fungus gnats in a laboratory experiment. Moreover, we discovered
      that volatile composition repeatedly switched in Asimitellaria between species
      adapted to long-tongued and short-tongued fungus gnats. Collectively, our results
      support the idea that recurrent scent-mediated speciation has taken place in the
      Asimitellaria-fungus gnat system.

PMID- 25615874
TI  - Malignant transformation of a lacrimal gland pleomorphic adenoma with pulmonary
      metastases.

PMID- 25615875
TI  - Development of gemcitabine-adsorbed magnetic gelatin nanoparticles for targeted
      drug delivery in lung cancer.
AB  - Magnetic iron oxide nanoparticles (IONPs) were coated with gelatin type B by
      means of the two-step desolvation method. Drug loading by adsorption was studied
      under various conditions such as different temperature, contact time, pH, and
      initial gemcitabine concentration. Further, Langmuir isotherm curves were
      constracted and constants were calculated. According to the Langmuir isotherm,
      the Gibbs free energy of the adsorption process at 25 degrees C was - 4.74
      kJ/mol. On the other hand, this value at 37 degrees C was - 7.86 kJ/mol. In vitro
      drug release was performed at pH levels of 5 and 7.4, with gemcitabine-loaded
      magnetic gelatin nanoparticles and free gemcitabine, and both the results were
      subsequently compared. 

PMID- 25615876
TI  - Pretreatment with pPolyHb attenuates H2O2-induced endothelial cell injury through
      inhibition of JNK/p38 MAPK pathway by upregulation of heme oxygenase-1.
AB  - Polymerized porcine hemoglobin (pPolyHb) exhibits a protective effect on
      ischemia/reperfusion of organ grafts. A series of experiments were performed to
      explore the underlying cytoprotective mechanisms of pPolyHb pretreatment on H2O2
      induced cell death and apoptosis. The results showed that the pretreatment
      augmented heme oxygenase-1 (HO-1) expression, and at the same time, decreased the
      phosphorylation of JNK/p38 mitogen-activated protein kinase (MAPK) and
      intracellular ROS generation in H2O2-treated HUVECs. Moreover, the inhibition of
      HO-1 expression by tin porphyrin (SnPP) abolished the protective effects of
      pPolyHb, which suggested that the cytoprotective effect of pPolyHb involves
      upregulating HO-1 and subsequently decreasing the phosphorylation of the JNK and
      p38 MAPK and ROS generation. 

PMID- 25615877
TI  - Biomedical and biological applications of quantum dots.
AB  - Quantum dots (QDs) as colloidal nanocrystalline semiconductors have exceptional
      photophysical properties, due to their quantum confinement effects. Depending on
      their sizes and chemical compositions, QDs emit different wavelengths over a
      broad range of the light spectrum, from visible to infrared. QDs are typically
      extensively used for optical applications due to their high extinction
      coefficient. This article reviews biomedical applications of QDs, especially the
      application of QDs in cell targeting, delivery, diagnostics, cancer therapy, and
      imaging for cancer research. 

PMID- 25615878
TI  - Sexually biased transcripts at early embryonic stages of the silkworm depend on
      the sex chromosome constitution.
AB  - In the silkworm, Bombyx mori, females are heterogametic (WZ) whereas males have
      two Z chromosomes. Femaleness of B. mori is determined by the presence of the W
      chromosome, suggesting that there is a dominant feminizing gene on this
      chromosome. Recently, by transcriptome analysis of B. mori embryos, we discovered
      that a single W-chromosome-derived PIWI-interacting RNA (piRNA) is the long
      sought primary determinant of femaleness in B. mori. However, sexual bias in the
      transcriptome of B. mori early embryos has not yet been well characterized. Using
      deep sequencing data from molecularly sexed RNA of B. mori embryos, we identified
      and characterized 157 transcripts that are statistically differentially expressed
      between male and female early embryos. Most of the female-biased transcripts were
      transposons or repeat sequences that are produced presumably from the W
      chromosome. Bioinformatic analysis revealed that these repetitive sequences are
      piRNA precursors. In contrast, male-biased genes were frequently transcribed from
      the Z chromosome, suggesting that dosage compensation in Z-linked genes does not
      occur or is incomplete at early embryonic stages. Our analysis has drawn a
      picture of a global landscape of sexually biased transcriptome during early B.
      mori embyogenesis and has suggested for the first time that most sexually biased
      embryonic transcripts depend on sex chromosomes.

PMID- 25615879
TI  - Enhanced dissolution and oral bioavailability of nifedipine by spontaneous
      emulsifying powders: effect of solid carriers and dietary state.
AB  - The objective of this study was to prepare spontaneous emulsifying powder (SEP)
      for improving dissolution and enhancing oral bioavailability of a poorly water
      soluble drug, nifedipine (NDP). In order to investigate the effects of solid
      carrier properties, such as surface area and pore size, and a concurrent food
      intake on absorption of NDP in rats, different SEP formulations were prepared by
      adsorbing liquid spontaneous emulsifying formulation (SEF), composing of polyoxyl
      35 castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether at
      a ratio of 1:1:8, onto various solid carriers (i.e., silica (FS), porous calcium
      silicate (PCS) and porous silicon dioxide). The solid characterization by
      scanning electron microscopy, differential scanning calorimetry and powder X-ray
      diffraction revealed the absence of crystalline NDP in the formulations. SEP also
      demonstrated excellent spontaneous emulsification properties similar to SEF. The
      droplet size of emulsions formed after dilution was less than 200 nm. The solid
      carriers (particularly PCS) had significant and positive effect in drug
      dissolution; the mean dissolution time of SEP containing PCS was considerably
      improved. SEP also provided a good stability after storage in accelerated and
      long-term conditions for 6 months. The bioavailability study resulted in enhanced
      values of C(max) and AUC for SEP formulations, when tested in both fasted and fed
      rats. Furthermore, comparing the AUC in fasted and fed rats, NDP powder exhibited
      a significant food effect. The difference in bioavailability of NDP in fed
      compared to fasted state can be avoided by using SEP.

PMID- 25615880
TI  - Mimicking microbial strategies for the design of mucus-permeating nanoparticles
      for oral immunization.
AB  - Dealing with mucosal delivery systems means dealing with mucus. The name mucosa
      comes from mucus, a dense fluid enriched in glycoproteins, such as mucin, which
      main function is to protect the delicate mucosal epithelium. Mucus provides a
      barrier against physiological chemical and physical aggressors (i.e., host
      secreted digestive products such as bile acids and enzymes, food particles) but
      also against the potentially noxious microbiota and their products. Intestinal
      mucosa covers 400m(2) in the human host, and, as a consequence, is the major
      portal of entry of the majority of known pathogens. But, in turn, some
      microorganisms have evolved many different approaches to circumvent this barrier,
      a direct consequence of natural co-evolution. The understanding of these
      mechanisms (known as virulence factors) used to interact and/or disrupt mucosal
      barriers should instruct us to a rational design of nanoparticulate delivery
      systems intended for oral vaccination and immunotherapy. This review deals with
      this mimetic approach to obtain nanocarriers capable to reach the epithelial
      cells after oral delivery and, in parallel, induce strong and long-lasting immune
      and protective responses. 

PMID- 25615881
TI  - The Cyclops for pulmonary delivery of aminoglycosides; a new member of the
      TwincerTM family.
AB  - Patients infected with pathogenic bacteria have to be treated with antibiotics.
      When the infection is in the lungs, as for instance in cystic fibrosis,
      bronchiectasis and tuberculosis, inhaled antibiotics have certain advantages over
      systemically administered antibiotics. In this study, it is shown that re
      designing the TwincerTM high dose disposable inhaler into a device named Cyclops
      enables effective dispersion of up to 50mg of pure spray dried tobramycin. This
      proves that spray dried tobramycin powders in the preferred size range for
      inhalation can be administered without applying complex particle engineering
      techniques and/or using excipients. Only some coarse sweeper crystals added
      separately are desired to minimise the inhaler losses to less than 20% at 4 kPa.
      The fine particle fractions <5 MUm of the aerosol obtained from the Cyclops
      closely resemble the primary particle size distribution of the spray dried
      tobramycin powder. Moreover, without any further optimisation the Cyclops
      performs good with other spray dried aminoglycosides such as kanamycin and
      amikacin too. Therefore, the results of this study show that with an appropriate
      inhaler design, adapted to the physico-chemical properties of a particular drug
      or drug class, excellent dispersion can be achieved for high doses of pure (spray
      dried) drug.

PMID- 25615882
TI  - Retinal gene delivery by adeno-associated virus (AAV) vectors: Strategies and
      applications.
AB  - Adeno-associated virus (AAV) vectors are the most widely used vehicle systems for
      neuronal gene transfer. This popularity is based on the non-pathogenic nature of
      AAVs and their versatility making them a multifunctional vector system for basic
      research and clinical applications. AAVs are successfully applied in clinical and
      pre-clinical gene therapy studies for inherited retinal disorders. Their
      excellent transduction profile and efficiency also boosted the use of AAV vectors
      in basic research. The AAV vector system can be easily modified and adjusted at
      multiple levels to allow for optimized and specific gene expression in target
      cells. Here, we will provide an overview on the AAV vector system and its
      applications focusing on gene transfer into retinal cells. Furthermore, we will
      outline and discuss strategies for the optimization of AAV gene transfer by
      modifications to the AAV vector expression cassette, the AAV capsid or the routes
      of vector administration. 

PMID- 25615883
TI  - Quality-of-life for individuals with a vestibular impairment following an
      acquired brain injury (ABI); the clients' perspective.
AB  - PRIMARY OBJECTIVE: To investigate how a vestibular deficit following an acquired
      brain injury (ABI) affects an individuals' quality-of-life. RESEARCH DESIGN: A
      qualitative exploratory design. PARTICIPANTS: Nine community dwelling individuals
      who experienced significant symptoms and limitations as a result of their
      vestibular deficits. METHODS: The individuals participated in face-to-face
      interviews with open ended questions. Data was analysed initially using a case
      study research approach, exploring the experience for each individual and then
      cross-case analysis to determine common themes for the group with the assistance
      of nVivo 10 qualitative analysis software. RESULTS: Thematic analysis determined
      four main themes arising from the interviews; (1) validation, (2) definitive
      diagnosis is more difficult amongst an array of ABI symptoms, (3) vestibular
      adaptation is more difficult in the presence of an ABI and (4) emotional and
      social. CONCLUSION: Individuals who suffer a brain injury and experience
      vestibular symptoms as part of their overall presentation are not diagnosed in a
      timely manner, with individuals, their families, associates and even health
      professionals feeling uncertain of the legitimacy of their reported symptoms. It
      is important that all patients who experience an acquired brain injury are
      screened for vestibular impairment and, if necessary, receive vestibular
      rehabilitation including explanation and education.

PMID- 25615884
TI  - 137Cs in puddle sediments as timescale tracer in urban environment.
AB  - The (137)Cs-based chronological approach is suggested to identify the age of
      urban landscapes and the chronology of pollution of soil in residential areas.
      Three main pivot points constitute the basis of the chronological approach:
      beginning of the Atomic Era in 1945, the maximum input in 1963 and the Chernobyl
      accident in 1986. Application of (137)Cs as a timescale tracer was tested on the
      example of Ekaterinburg, a city in the Middle Urals region of Russia. The
      sampling of recent urban sediments of micro water bodies (puddles) was carried
      out in 210 locations in 2007-2010. The concentrations of Pb, Zn, Cu, Ni, Co, Mn
      and Fe, and activity concentrations of (137)Cs were measured. It was found that
      the (137)Cs concentrations in the puddle sediments correlated with the age of
      surrounding buildings determined by the year of construction. The correlations
      between the concentrations of metals and (137)Cs in the puddle sediments
      identified the major pollutants of the urban area, assessing their background
      concentrations and obtaining the average annual inputs. 

PMID- 25615885
TI  - Systematic review of systematic reviews for the management of urinary
      incontinence and promotion of continence using conservative behavioural
      approaches in older people in care homes.
AB  - AIM: To synthesize evidence from systematic reviews on the management of urinary
      incontinence and promotion of continence using conservative/behavioural
      approaches in older people in care homes to inform clinical practice, guidelines
      and research. BACKGROUND: Incontinence is highly prevalent in older people in
      care home populations. DESIGN: Systematic review of systematic reviews with
      narrative synthesis. DATA SOURCES: Electronic searches of published systematic
      reviews in English using MEDLINE and CINAHL with no date restrictions up to
      September 2013. Searches supplemented by hand searching and electronic searching
      of Cochrane Library and PROSPERO. REVIEW METHODS: PRISMA statement was followed,
      as were established methods for systematic review of systematic reviews. RESULTS:
      Five systematic reviews of high quality were included, three specific to
      intervention studies and two reviewed descriptive studies. Urinary incontinence
      was the primary outcome in three reviews with factors associated with the
      management of urinary incontinence the primary outcome for the other reviews.
      CONCLUSION: Toileting programmes, in particular prompted voiding, with use of
      incontinence pads are the main conservative behavioural approach for the
      management of incontinence and promotion of continence in this population with
      evidence of effectiveness in the short term. Evidence from associated factors;
      exercise, mobility, comorbidities, hydration, skin care, staff perspectives,
      policies and older people's experiences and preference are limited. The majority
      of evidence of effectiveness are from studies from one country which may or may
      not be transferable to other care home populations. Future international studies
      are warranted of complex combined interventions using mixed methods to provide
      evidence of effectiveness, context of implementation and economic evaluation.

PMID- 25615887
TI  - Rhombohedral prussian white as cathode for rechargeable sodium-ion batteries.
AB  - A novel air-stable sodium iron hexacyanoferrate (R-Na1.92Fe[Fe(CN)6]) with
      rhombohedral structure is demonstrated to be a scalable, low-cost cathode
      material for sodium-ion batteries exhibiting high capacity, long cycle life, and
      good rate capability. The cycling mechanism of the iron redox is clarified and
      understood through synchrotron-based soft X-ray absorption spectroscopy, which
      also reveals the correlation between the physical properties and the cell
      performance of this novel material. More importantly, successful preparation of a
      dehydrated iron hexacyanoferrate with high sodium-ion concentration enables the
      fabrication of a discharged sodium-ion battery with a non-sodium metal anode, and
      the manufacturing feasibility of low cost sodium-ion batteries with existing
      lithium-ion battery infrastructures has been tested. 

PMID- 25615886
TI  - Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene
      network in human epileptic hippocampus.
AB  - Gene-regulatory network analysis is a powerful approach to elucidate the
      molecular processes and pathways underlying complex disease. Here we employ
      systems genetics approaches to characterize the genetic regulation of
      pathophysiological pathways in human temporal lobe epilepsy (TLE). Using
      surgically acquired hippocampi from 129 TLE patients, we identify a gene
      regulatory network genetically associated with epilepsy that contains a
      specialized, highly expressed transcriptional module encoding proconvulsive
      cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a
      mouse model of TLE using 100 epileptic and 100 control hippocampi shows the
      proconvulsive module is preserved across-species, specific to the epileptic
      hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the
      trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3),
      and demonstrate that SESN3 positively regulates the module in macrophages,
      microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms
      the regulation of the transcriptional module, and attenuates chemically induced
      behavioural seizures in vivo. 

PMID- 25615888
TI  - Psychosocial aspects of closed- and open-loop insulin delivery: closing the loop
      in adults with Type 1 diabetes in the home setting.
AB  - AIMS: To explore the psychosocial experiences of closed-loop technology and to
      compare ratings of closed- and open-loop technology for adults with Type 1
      diabetes taking part in a randomized crossover study. METHODS: Adults (aged > 18
      years) on insulin pump therapy were recruited to receive a first phase of either
      real-time continuous glucose monitoring with overnight closed-loop or real-time
      continuous glucose monitoring alone (open-loop) followed by a second phase of the
      alternative treatment in random order, at home for 4 weeks, unsupervised.
      Participants were invited to share their views in semi-structured interviews. The
      impact of the closed-loop technology, positive and negative aspects of living
      with the device overnight, along with the hopes and anxieties of the
      participants, were explored. RESULTS: The participants in the trial were 24
      adults with a mean (sd) age of 43 (12) years, of whom 54% were men. The mean
      (range) interview duration was 26 (12-46) min. Content and thematic analysis
      showed the following key positive themes: improved blood glucose control (n =
      16); reassurance/reduced worry (n = 16); improved overnight control leading to
      improved daily functioning and diabetes control (n = 16); and improved sleep (n =
      8). The key negative themes were: technical difficulties (n = 24); intrusiveness
      of alarms (n = 13); and size of equipment (n = 7). Of the 24 participant, 20
      would recommend the closed-loop technology. CONCLUSIONS: Closed-loop therapy has
      positive effects when it works in freeing participants from the demands of self
      management. The downside was technical difficulties, particularly concerning the
      pump and 'connectivity', which it is hoped will improve. Future research should
      continue to explore the acceptability of the closed-loop system as a realistic
      therapy option, taking account of user concerns as new systems are designed.
      Failure to do this may reduce the eventual utility of new systems.

PMID- 25615889
TI  - Somatosensory assessment and treatment after stroke: An evidence-practice gap.
AB  - BACKGROUND/AIM: Loss of body sensations is common after stroke, impacting
      negatively on recovery and performance of activities of daily living. Despite
      advances in the evidence for the assessment and treatment of somatosensory
      impairment post-stroke, the translation from research into clinical practice has
      been slow. The aim of this study was to determine current clinical practice of
      occupational therapists and physiotherapists in the assessment and treatment of
      somatosensory impairment post-stroke. METHODS: A cross-sectional, self
      administered online survey of occupational therapists and physiotherapists
      currently working with stroke clients in Australian health organisations,
      identified through an audit of stroke rehabilitation services and a professional
      member association. RESULTS: 172 clinicians, 62.8% occupational therapists and
      37.2% physiotherapists currently working with stroke clients completed the
      survey. Most respondents (93.0%) indicated routinely assessing for sensory loss
      in stroke clients. The most commonly used measures were light touch and
      proprioception, with the majority (70.4%) not using standardised measures. Most
      respondents (97.7%) reported providing treatment to address sensory impairment,
      with compensatory strategies and sensory re-education the two most frequently
      reported. Evidence-based treatment choices were not common and therapists
      frequently relied on colleagues' opinions and previous experience to inform
      practice. Therapists commonly experienced barriers to implementing evidence-based
      sensory rehabilitation, including time constraints, large caseloads and lack of
      access to evidence-based somatosensory assessment and treatment resources.
      CONCLUSIONS: Most therapists perceived somatosensory assessment and treatment as
      important. However, frequently utilised methods lack a sound theoretical or
      empirical basis. Despite published evidence regarding somatosensory assessment
      and treatment, an evidence-practice gap exists.

PMID- 25615890
TI  - The molecular circuitry of brassinosteroid signaling.
AB  - Because they are tethered in space, plants have to make the most of their local
      growth environment. In order to grow in an ever-changing environment, plants
      constantly remodel their shapes. This adaptive attribute requires the
      orchestration of complex environmental signals at the cellular and organismal
      levels. A battery of small molecules, classically known as phytohormones, allows
      plants to change their body plan by using highly integrated signaling networks
      and transcriptional cascades. Amongst these hormones, brassinosteroids (BRs), the
      polyhydroxylated steroid of plants, influence plant responsiveness to the local
      environment and exquisitely promote, or interfere with, many aspects of plant
      development. The molecular circuits that wire steroid signals at the cell surface
      to the promoters of thousands of genes in the nucleus have been defined in the
      past decade. This review recapitulates how the transduction of BR signals impacts
      the temporally unfolding programs of plant growth. First, we summarize the
      paradigmatic BR signaling pathway acting primarily in cellular expansion.
      Secondly, we describe the current wiring diagram and the temporal dynamics of the
      BR signal transduction network. And finally we provide an overview of how key
      players in BR signaling act as molecular gates to transduce BR signals onto other
      signaling pathways.

PMID- 25615891
TI  - Chromatic biosensor for detection of phosphinothricin acetyltransferase by use of
      polydiacetylene vesicles encapsulated within automatically generated
      immunohydrogel beads.
AB  - We developed a simple and sensitive colorimetric biosensor in the form of
      microparticles by using polydiacetylene (PDA) vesicles encapsulated within a
      hydrogel matrix for the detection of phosphinothricin acetyltransferase (PAT)
      protein, which is one of the most important marker proteins in genetically
      modified (GM) crops. Although PDA is commonly used as a sensing material due to
      its unique colorimetric properties, existing PDA biosensors are ineffective due
      to their low sensitivity as well as their lack of robustness. To overcome these
      disadvantages, we devised immunohydrogel beads made of anti-PAT-conjugated PDA
      vesicles embedded at high density within a poly(ethylene glycol) diacrylate (PEG
      DA) hydrogel matrix. In addition, the construction of immunohydrogel beads was
      automated by use of a microfluidic device. In the immunoreaction, the sensitivity
      of antibody-conjugated PDA vesicles was significantly amplified, as monitored by
      the unaided eye. The limit of detection for target molecules reached as low as 20
      nM, which is sufficiently low enough to detect target materials in GM organisms.
      Collectively, the results show that immunohydrogel beads constitute a promising
      colorimetric sensing platform for onsite testing in a number of fields, such as
      the food and medical industries, as well as warfare situations. 

PMID- 25615892
TI  - Effects of voice rehabilitation on health-related quality of life, communication
      and voice in laryngeal cancer patients treated with radiotherapy: a randomised
      controlled trial.
AB  - OBJECTIVE: This study aims to assess the effect of voice rehabilitation on health
      related quality of life (HRQL) and communication experience for laryngeal cancer
      patients treated with radiotherapy. METHOD: This prospective randomised
      controlled trial included 74 patients with Tis-T4 laryngeal cancer treated
      curatively by radiotherapy, of which 37 constituted the intervention group
      receiving voice rehabilitation and 37 patients as a control group. Patients were
      followed at one and six months post-radiotherapy, with voice rehabilitation
      conducted between these time-points. Endpoints included patient reported
      outcomes, including HRQL as measured by European Organisation for Research and
      Treatment of Cancer (EORTC) Core30 (C30) and Head & Neck35 (H&N35) as well as
      communication function as measured by Swedish Self-Evaluation of Communication
      Experiences after Laryngeal cancer (S-SECEL). RESULTS: The intervention group
      reported statistically significant improvements in communication experience as
      measured by S-SECEL environmental, attitudinal and total score domains compared
      to the control group. Similar improvements were seen in EORTC H&N35 Speech domain
      and the EORTC C30 domain Global quality of life. Moderate correlations were noted
      (r = 0.51-0.59) between three of four S-SECEL domains and the EORTC domains
      Speech and Global quality of life. CONCLUSION: Laryngeal cancer patients treated
      with radiotherapy who receive voice rehabilitation appear to experience
      beneficial effects on communication function and selected HRQL domains. Voice
      rehabilitation following radiotherapy is recommended but further research
      investigating potential target groups and long-term effects is required.

PMID- 25615893
TI  - Treatment tolerance of particle therapy in pediatric patients.
AB  - Curative treatment of pediatric cancer not only focuses on long-term survival,
      but also on reducing treatment-related side effects. Advantages of particle
      therapy are mainly due to their physical ability of significantly reducing
      integral dose. METHODS: Between January 2009 and December 2012, we treated 83
      pediatric patients (aged 21 and younger) at the Heidelberg Ion Therapy Center at
      University Hospital of Heidelberg (HIT). In total 56 patients (67%) received
      proton irradiation, while 25 (30%) patients were treated with carbon ions (C12).
      Two patients received both treatments (3%). Treatment toxicity was analyzed
      retrospectively and documented according to the CTCAE/RTOG classification. In a
      second step, treatment toxicity from ion therapy was analyzed in comparison to
      treatment toxicity during photon irradiation of a comparable historical group of
      19 pediatric patients. RESULTS: In all patients, particle therapy was tolerated
      well (median follow-up time 3.7 months), children (20 patients) with at least two
      follow-up visits showed a median follow-up time of 10.2 months. During the first
      two months patients mainly suffered from radiogenic skin reaction (63%),
      mucositis (30%), headache and dizziness (35%) as well as nausea and vomiting
      (13%). Severe toxicity reaction (grade II-IV) was only seen in patients who had
      intensive simultaneous chemotherapy or who had undergone several operations in
      the irradiated area before radiotherapy (18%). Treatment toxicity during ion
      therapy was comparable to treatment toxicity from photon irradiation of a
      historical group. CONCLUSIONS: In comparison to conventional therapy, patients
      with particle therapy do not suffer from increased acute treatment-related
      toxicity during the first months. More experience with particle therapy will be
      needed during the next years to help to thoroughly evaluate the high potential of
      ion therapy.

PMID- 25615894
TI  - What Happens to Mental Health Court Noncompleters?
AB  - Mental health court (MHC) research consistently finds that defendants who
      successfully complete and graduate from the court are less likely to recidivate
      than those who do not. However, research has not assessed what happens to these
      noncompleters once they are sent back to traditional court. Using follow-up data
      on six years of noncompleters from pre-adjudication MHC, we examine what happens
      to these defendants in traditional court. Findings suggest that 63.7% of
      defendants' charges were dismissed, 21.0% received probation, and 15.3% were
      sentenced to incarceration. We examine the time to disposition and differences in
      defendant characteristics and disposition outcome as well as the relationship
      between disposition and subsequent recidivism. Results suggest that more severe
      punishments in traditional court are associated with recidivism. Logistic
      regression analysis shows that defendants whose charges were dismissed in
      traditional court were less likely to recidivate than those who were sentenced to
      probation or incarceration. Our findings highlight the need for future MHC
      evaluations to consider traditional court outcomes and support trends towards
      post-adjudication courts.

PMID- 25615895
TI  - Evaluating the possibility of using acetone-butanol-ethanol (ABE) fermentation
      wastewater for bacterial cellulose production by Gluconacetobacter xylinus.
AB  - To reduce the cost of bacterial cellulose (BC) production, the possibility of
      using acetone-butanol-ethanol (ABE) fermentation wastewater with high COD value
      (18 050 mg l(-1) ) for BC production by Gluconacetobacter xylinus was evaluated.
      After 7 days of fermentation, the highest BC yield (1.34 g l(-1) ) was obtained.
      The carbon sources including sugars (glucose and xylose), organic acids (acetic
      acid and butyric acid) and alcohol compounds (ethanol and butanol) were utilized
      by G. xylinus simultaneously during fermentation. Although the COD decrease ratio
      (about 14.7%) was low, the highest BC yield on COD consumption (56.2%, g g(-1) )
      was relatively high and the remaining wastewater could be used for further BC
      fermentation. Besides, the environment of ABE fermentation wastewater showed
      small influence on the BC structure by comparison with the BC products obtained
      in traditional HS medium using field emission scanning electron microscope (FE
      SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD).
      Overall, ABE fermentation wastewater is one promising substrate for BC
      production. SIGNIFICANCE AND IMPACT OF THE STUDY: The possibility of using
      acetone-butanol-ethanol (ABE) fermentation wastewater for bacterial cellulose
      (BC) production by Gluconacetobacter xylinus was evaluated in this study. This is
      the first time that ABE fermentation wastewater was used as substrate for BC
      fermentation. The results provide detail information of metabolism of G. xylinus
      in ABE fermentation wastewater and the influence of wastewater environment on the
      structure of BC samples. Overall, this bioconversion could reduce the cost of BC
      production greatly.

PMID- 25615896
TI  - Editorial comment.

PMID- 25615897
TI  - IL36RN gene analysis of two Japanese patients with generalized pustular
      psoriasis.

PMID- 25615898
TI  - Severe contact dermatitis due to a metal scratcher.

PMID- 25615899
TI  - Acitretin induces remission in generalized eruptive keratoacanthoma of
      Grzybowski.

PMID- 25615900
TI  - Effects of chemical complexity on the autoxidation mechanisms of endocyclic
      alkene ozonolysis products: from methylcyclohexenes toward understanding alpha
      pinene.
AB  - Formation of highly oxidized, multifunctional products in the ozonolysis of three
      endocyclic alkenes, 1- methylcyclohexene, 4-methylcyclohexene, and alpha-pinene,
      was investigated using a chemical ionization atmospheric pressure interface time
      of-flight (CI-APi-TOF) mass spectrometer with a nitrate ion (NO3(-)) based
      ionization scheme. The experiments were performed in borosilicate glass flow tube
      reactors at room temperature (T = 293 +/- 3 K) and at ambient pressure. An
      ensemble of oxidized monomer and dimer products was detected, with elemental
      compositions obtained from the high-resolution mass spectra. The monomer product
      distributions have O/C ratios from 0.8 to 1.6 and can be explained with an
      autocatalytic oxidation mechanism (=autoxidation) where the oxygen-centered
      peroxy radical (RO2) intermediates internally rearrange by intramolecular
      hydrogen shift reactions, enabling more oxygen molecules to attach to the carbon
      backbone. Dimer distributions are proposed to form by homogeneous peroxy radical
      recombination and cross combination reactions. These conclusions were supported
      by experiments where H atoms were exchanged to D atoms by addition of D2O to the
      carrier gas flow. Methylcyclohexenes were observed to autoxidize in accordance
      with our previous work on cyclohexene, whereas in alpha-pinene ozonolysis
      different mechanistic steps are needed to explain the products observed. 

PMID- 25615901
TI  - The genetics of aneurysms: a complex pathophysiology requiring complex analysis.

PMID- 25615902
TI  - Spontaneous object and movement representations in 4-month-old human infants and
      albino Swiss mice.
AB  - Can young infants decompose visual events into independent representations of
      objects and movements? Previous studies suggest that human infants may be born
      with the notion of objects but there is little evidence for movement
      representations during the first months of life. We devised a novel Rapid Visual
      Recognition Procedure to test whether the nervous system is innately disposed for
      the conceptual decomposition of visual events. We show that 4-month-old infants
      can spontaneously build object and movement representations and recognize these
      in partially matching test events. Also albino Swiss mice that were tested on a
      comparable procedure could spontaneously build detailed mental representations of
      moving objects. Our results dissociate the ability to conceptually decompose
      physical events into objects and spatio-temporal relations from various types of
      human and non-human specific experience, and suggest that the nervous system is
      genetically predisposed to anticipate the representation of objects and movements
      in both humans and non-human species. 

PMID- 25615903
TI  - Using motivational interviewing in the community pharmacy to increase adult
      immunization readiness: A pilot evaluation.
AB  - OBJECTIVES: To investigate whether the use of motivational interviewing (MI) in
      the community pharmacy improves immunization readiness and rates for hepatitis B,
      hepatitis A/B combination, herpes zoster, pneumococcal, and tetanus-diphtheria
      acellular pertussis immunizations. SETTING: Kroger Pharmacy. PRACTICE
      DESCRIPTION: Grocery store pharmacies located in the Atlanta, GA, metropolitan
      area offering a variety of patient care services, including medication therapy
      management and immunizations. PRACTICE INTERVENTION: Patients were identified
      during workflow, and MI encounters were initiated to those eligible to receive
      hepatitis A/B combination, hepatitis B, herpes zoster, pneumococcal and/or
      tetanus-diphtheria-acellular pertussis vaccines. EVALUATION: Following each
      encounter, pharmacists completed patient demographic information and responses to
      5-point Likert scale questions assessing patient readiness to receive
      immunizations at the beginning and end of the encounter, and if follow-up
      occurred, 5-point Likert scale questions assessing pharmacists' perception of
      using MI. RESULTS: Immunization rates at the intervention site did not
      significantly increase due to the small sample size and other project
      limitations. Patient readiness to receive immunizations improved from the
      beginning to the end of the MI encounter and was statistically significant for
      hepatitis B (P = 0.001) and pneumococcal (P = 0.033) vaccines. Pharmacists agreed
      MI was an effective tool to discuss immunizations, agreed they could communicate
      more effectively about immunizations, and agreed MI could be incorporated into
      the community pharmacy workflow. CONCLUSION: Motivational interviewing may be a
      useful tool for community pharmacists to use in discussing immunizations. Larger
      studies need to be completed to determine the impact MI could have on
      immunization readiness and rates in the community pharmacy.

PMID- 25615904
TI  - A Long-Term Model of the Glucose-Insulin Dynamics of Type 1 Diabetes.
AB  - A new glucose-insulin model is introduced which fits with the clinical data from
      in- and outpatients for two days. Its stability property is consistent with the
      glycemia behavior for type 1 diabetes. This is in contrast to traditional glucose
      insulin models. Prior models fit with clinical data for a few hours only or
      display some nonnatural equilibria. The parameters of this new model are
      identifiable from standard clinical data as continuous glucose monitoring,
      insulin injection, and carbohydrate estimate. Moreover, it is shown that the
      parameters from the model allow the computation of the standard tools used in
      functional insulin therapy as the basal rate of insulin and the insulin
      sensitivity factor. This is a major outcome as they are required in therapeutic
      education of type 1 diabetic patients. 

PMID- 25615905
TI  - Direct Gaze Estimation Based on Nonlinearity of EOG.
AB  - Electrooculography (EOG) is one of the measures used to estimate the direction of
      a person's gaze; however, conventional EOG techniques suffer from a drift issue
      which makes it difficult to extract an accurate absolute eye angle. The technique
      proposed here is based on the nonlinearity of the EOG and offers a practical
      solution to this problem. It estimates the absolute eye angles before and after a
      saccade, which cancels the offset due to the drift. Additionally, it does not
      require any effort from the user or any target, but instead uses only the
      difference of the EOGs. Experiments with five subjects confirm that the proposed
      technique can estimate the absolute eye angle with an error of less than 4(
      degrees ). They also show improvements are achieved with several options such as
      weighting and multiple saccades. The technique will contribute to practical EOG
      based interaction systems. 

PMID- 25615906
TI  - Sensitivity of Noninvasive Cardiac Electrophysiological Imaging to Variations in
      Personalized Anatomical Modeling.
AB  - OBJECTIVE: Noninvasive cardiac electrophysiological (EP) imaging techniques rely
      on anatomically-detailed heart-torso models derived from high-quality tomographic
      images of individual subjects. However, anatomical modeling involves variations
      that lead to unresolved uncertainties in the outcome of EP imaging, bringing
      questions to the robustness of these methods in clinical practice. In this study,
      we design a systematic statistical approach to assess the sensitivity of EP
      imaging methods to the variations in personalized anatomical modeling. METHODS:
      We first quantify the variations in personalized anatomical models by a novel
      application of statistical shape modeling. Given the statistical distribution of
      the variation in personalized anatomical models, we then employ unscented
      transform to determine the sensitivity of EP imaging outputs to the variation in
      input personalized anatomical modeling. RESULTS: We test the feasibility of our
      proposed approach using two of the existing EP imaging methods: epicardial-based
      electrocardiographic imaging and transmural electrophysiological imaging. Both
      phantom and real-data experiments show that variations in personalized anatomical
      models have negligible impact on the outcome of EP imaging. CONCLUSION: This
      study verifies the robustness of EP imaging methods to the errors in personalized
      anatomical modeling and suggests the possibility to simplify the process of
      anatomical modeling in future clinical practice. SIGNIFICANCE: This study
      proposes a systematic statistical approach to quantify anatomical modeling
      variations and assess their impact on EP imaging, which can be extended to find a
      balance between the quality of personalized anatomical models and the accuracy of
      EP imaging that may improve the clinical feasibility of EP imaging.

PMID- 25615908
TI  - Lanthanide(III) complexation with an amide derived pyridinophane.
AB  - Herein we report a detailed investigation of the solid state and solution
      structures of lanthanide(III) complexes with the 18-membered pyridinophane ligand
      containing acetamide pendant arms TPPTAM (TPPTAM = 2,2',2"-(3,7,11-triaza
      1,5,9(2,6)-tripyridinacyclododecaphane-3,7,11-triyl)triacetamide). The ligand
      crystallizes in the form of a clathrated hydrate, where the clathrated water
      molecule establishes hydrogen-bonding interactions with the amide NH groups and
      two N atoms of the macrocycle. The X-ray structures of 13 different Ln(3+)
      complexes obtained as the nitrate salts (Ln(3+) = La(3+)-Yb(3+), except Pm(3+))
      have been determined. Additionally, the X-ray structure of the La(3+) complex
      obtained as the triflate salt was also obtained. In all cases the ligand provides
      9-fold coordination to the Ln(3+) ion, ten coordination being completed by an
      oxygen atom of a coordinated water molecule or a nitrate or triflate anion. The
      bond distances of the metal coordination environment show a quadratic change
      along the lanthanide series, as expected for isostructural series of Ln(3+)
      complexes. Luminescence lifetime measurements obtained from solutions of the
      Eu(3+) and Tb(3+) complexes in H2O and D2O point to the presence of a water
      molecule coordinated to the metal ion in aqueous solutions. The analysis of the
      Ln(3+)-induced paramagnetic shifts indicates that the complexes are ten
      coordinated throughout the lanthanide series from Ce(3+) to Yb(3+), and that the
      solution structure is very similar to the structures observed in the solid state.
      The complexes of the light Ln(3+) ions are fluxional due to a fast
      Delta(lambdalambdalambdalambdalambdalambda) <->
      Lambda(deltadeltadeltadeltadeltadelta) interconversion that involves the
      inversion of the macrocyclic ligand and the rotation of the acetamide pendant
      arms. The complexes of the small Ln(3+) ions are considerably more rigid, the
      activation free energy determined from VT (1)H NMR for the Lu(3+) complex being
      DeltaG(?)298 = 72.4 +/- 5.1 kJ mol(-1). 

PMID- 25615907
TI  - Tubulin-binding agents down-regulate matrix metalloproteinase-2 and -9 in human
      hormone-refractory prostate cancer cells - a critical role of Cdk1 in mitotic
      entry.
AB  - Tubulin is an important target for anticancer therapy. Taxanes and vinca
      alkaloids are two groups of tubulin-binding agents in cancer chemotherapy.
      Besides tubulin binding, these groups of agents can also down-regulate protein
      levels of matrix metalloproteinase (MMP)-2 and -9, two important cancer
      associated zinc-dependent endopeptidases in invasion and metastasis. However, the
      mechanism of action waits to be explored. In this study, protein levels but not
      mRNA expressions of MMP-2 and -9 were down-regulated by paclitaxel (a microtubule
      stabilization agent), vincristine and evodiamine (two tubulin-depolymerization
      agents). These agents induced an increase of protein expression of cyclin B1,
      MPM2 (mitosis-specific phosphoprotein) and polo-like kinase (PLK) 1
      phosphorylation. The data showed a negative relationship between the levels of
      mitotic proteins and MMP-2 and -9 expressions. MG132 (a specific cell-permeable
      proteasome inhibitor) blocked mitotic entry and arrested cell cycle at G2 phase,
      preventing down-regulation of MMP-2 and -9. Cell cycle synchronization
      experiments by thymidine block or nocodazole treatment showed that mitotic exit
      inhibited the down-regulation of MMP-2 and -9, confirming negative relationship
      between cell mitosis and protein levels of MMP-2 and -9 expressions. Cyclin
      dependent kinase (Cdk) 1 is a key kinase in mitotic entry. Knockdown of Cdk1
      almost completely inhibited the down-regulation of MMP-2 and -9 induced by
      tubulin-binding agents. In conclusion, the data suggest that mitotic entry and
      Cdk1 plays a central role in down-regulation of MMP-2 and -9 protein expressions.
      Tubulin-binding agents cause mitotic arrest and Cdk1 activation, which may
      contribute largely to the down-regulation of both MMP-2 and -9 expressions. 

PMID- 25615909
TI  - Large conductance Ca2+-activated K+ (BK) channels promote secretagogue-induced
      transition from spiking to bursting in murine anterior pituitary corticotrophs.
AB  - Anterior pituitary corticotroph cells are a central component of the hypothalamic
      pituitary-adrenal (HPA) axis essential for the neuroendocrine response to stress.
      Corticotrophs are excitable cells that receive input from two hypothalamic
      secretagogues, corticotrophin-releasing hormone (CRH) and arginine vasopressin
      (AVP) to control the release of adrenocorticotrophic hormone (ACTH). Although
      corticotrophs are spontaneously active and increase in excitability in response
      to CRH and AVP the patterns of electrical excitability and underlying ionic
      conductances are poorly understood. In this study, we have used
      electrophysiological, pharmacological and genetic approaches coupled with
      mathematical modelling to investigate whether CRH and AVP promote distinct
      patterns of electrical excitability and to interrogate the role of large
      conductance calcium- and voltage-activated potassium (BK) channels in spontaneous
      and secretagogue-induced activity. We reveal that BK channels do not play a
      significant role in the generation of spontaneous activity but are critical for
      the transition to bursting in response to CRH. In contrast, AVP promotes an
      increase in single spike frequency, a mechanism independent of BK channels but
      dependent on background non-selective conductances. Co-stimulation with CRH and
      AVP results in complex patterns of excitability including increases in both
      single spike frequency and bursting. The ability of corticotroph excitability to
      be differentially regulated by hypothalamic secretagogues provides a mechanism
      for differential control of corticotroph excitability in response to different
      stressors.

PMID- 25615911
TI  - Social exclusion and shame in obesity.
AB  - Weight bias often results in the social exclusion of individuals with obesity.
      The direct, short-term psychological effects of social exclusion in obesity have
      not been investigated yet. This study experimentally tests whether social
      exclusion elicits stronger negative emotions in individuals with obesity compared
      to normal-weight controls. Specifically, we test whether social exclusion has a
      specific impact on shame. In total, N=299 individuals (n=130 with body mass index
      [BMI]<=30 and n=169 with BMI>30) were randomly assigned to a social exclusion
      condition or a control condition that was implemented with an online Cyberball
      paradigm. Before and after, they filled out questionnaires assessing state
      emotionality. Social exclusion increased negative emotionality in both groups
      compared to the control condition (p<0.001) according to a multivariate ANOVA.
      However, the interaction of group and social exclusion was also significant
      (p=0.035) and arose from a significant, specific increase of shame in the group
      with obesity during social exclusion (p<0.001, Cohen's d=0.7). When faced with
      social exclusion, individuals with obesity do not respond with more intensive
      negative emotions in general compared to controls, but with a specific increase
      in shame. As social exclusion is frequent in individuals with obesity,
      psychological interventions focussing shame-related emotional distress could be
      crucial. 

PMID- 25615910
TI  - An efficient and highly diastereoselective synthesis of GSK1265744, a potent HIV
      integrase inhibitor.
AB  - A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described.
      The synthesis is highlighted by an efficient construction of the densely
      functionalized pyridinone core as well as a highly diastereoselective formation
      of the acyl oxazolidine moiety. The latter exploits the target molecule's ability
      to chelate to Mg(2+), a key feature in the integrase inhibitor's mechanism of
      action. 

PMID- 25615912
TI  - Interfacial effects on lithium superoxide disproportionation in Li-O2 batteries.
AB  - During the cycling of Li-O2 batteries the discharge process gives rise to
      dynamically evolving agglomerates composed of lithium-oxygen nanostructures;
      however, little is known about their composition. In this paper, we present
      results for a Li-O2 battery based on an activated carbon cathode that indicate
      interfacial effects can suppress disproportionation of a LiO2 component in the
      discharge product. High-intensity X-ray diffraction and transmission electron
      microscopy measurements are first used to show that there is a LiO2 component
      along with Li2O2 in the discharge product. The stability of the discharge product
      was then probed by investigating the dependence of the charge potential and Raman
      intensity of the superoxide peak with time. The results indicate that the LiO2
      component can be stable for possibly up to days when an electrolyte is left on
      the surface of the discharged cathode. Density functional calculations on
      amorphous LiO2 reveal that the disproportionation process will be slower at an
      electrolyte/LiO2 interface compared to a vacuum/LiO2 interface. The combined
      experimental and theoretical results provide new insight into how interfacial
      effects can stabilize LiO2 and suggest that these interfacial effects may play an
      important role in the charge and discharge chemistries of a Li-O2 battery. 

PMID- 25615913
TI  - Sweat-inducing physiological challenges do not result in acute changes in hair
      cortisol concentrations.
AB  - Hair cortisol concentrations (HCC) are assumed to provide a stable, integrative
      marker of long-term systemic cortisol secretion. However, contrary to this
      assumption, some recent observations have raised the possibility that HCC may be
      subject to acute influences, potentially related to cortisol incorporation from
      sweat. Here, we provide a first detailed in vivo investigation of this
      possibility comprising two independent experimental studies: study I (N=42) used
      a treadmill challenge to induce sweating together with systemic cortisol
      reactivity while in study II (N=52) a sauna bathing challenge induced sweating
      without systemic cortisol changes. In both studies, repeated assessments of HCC,
      salivary cortisol, cortisol in sweat and individuals' sweating rate (single
      assessment) were conducted on the experimental day and at a next-day follow-up.
      Results across the two studies consistently revealed that HCC were not altered by
      the acute interventions. Further, HCC were found to be unrelated to acute
      salivary cortisol reactivity, sweat cortisol levels, sweating rate or the time of
      examination. In line with previous data, cortisol levels in sweat were strongly
      related to total salivary cortisol output across the examined periods. The
      present results oppose recent case report data by showing that single sweat
      inducing interventions do not result in acute changes in HCC. Our data also
      tentatively speak against the notion that cortisol in sweat may be a dominant
      source of HCC. Further, our findings also indicate that HCC are not subject to
      diurnal variation. This research provides further support for hair cortisol
      analysis as a marker of integrated long-term systemic cortisol secretion. 

PMID- 25615914
TI  - Patient knowledge and expectations prior to receiving implant-supported
      restorations.
AB  - PURPOSE: Implant dentistry has revolutionized the treatment of partially and
      completely edentulous patients. The aims of this study were to explore what made
      patients choose implant treatment and their prior knowledge and expectations of
      this treatment option. MATERIALS AND METHODS: A study population of 117 subjects
      was selected from 248 referred possible candidates for implant therapy. The
      subjects answered a questionnaire regarding implant dentistry prior to
      professional consultation at two hospital/university-based centers and one
      private implant center. RESULTS: In most cases, the choice of treatment was
      motivated by expectations of improved chewing/function (46.0%), appearance
      (19.5%), or both (18.6%). Improved chewing/function and improved appearance were
      rated "very important" by 96.5% and 86.1% of patients, respectively.
      Surprisingly, 57.4% reported that the cost of treatment did not play a role in
      their decision. Only 6.0% claimed to have much prior knowledge about the
      treatment and 33.6% had a realistic perception about the length of anticipated
      service. Patients first received implant-related information primarily (62.9%)
      from dentists, and 75.2% thought their dentist gave the most useful information.
      Significant positive associations were found between knowledge about the
      treatment, the need for periodic professional oral health maintenance, and
      expected treatment time. CONCLUSION: Patients seek implant therapy primarily to
      improve chewing function and esthetics, whereas cost seems to be less important.
      Prior to treatment, many patients lack precise information on the importance of
      necessary implant-related hygiene measures and implant longevity. The general
      dentist is the primary source of information.

PMID- 25615915
TI  - Effect of a modified stepped osteotomy on the primary stability of dental
      implants in low-density bone: a cadaver study.
AB  - PURPOSE: The aim of this study was to examine the effect of an alternative
      surgical technique on endosseous dental implant stability parameters in Class D4
      bone. Differences between insertion torque (IT) and implant stability quotient
      (ISQ) produced by a conventional osteotomy versus a modified stepped osteotomy
      were examined. Correlations between IT, density in Hounsfield units (HU), and ISQ
      were also examined. MATERIALS AND METHODS: Computed tomographic scans were taken
      of 16 cadaver heads to determine bone density at maxillary implant recipient
      sites, which ranged from 173.4 to 312.1 HU. Twenty-two implants were placed in
      sites with Misch Class D4 bone; control sites received 11 conventional
      osteotomies and test sites 11 modified stepped osteotomies. Maximum IT was
      recorded with an implant motor and confirmed with a torque driver, and ISQs were
      measured. Significant differences were analyzed with a Wilcoxon signed rank test,
      and correlations were analyzed with the Pearson test. RESULTS: The mean IT in the
      control group was 15.91 Ncm, and in the test group it was 26.82 Ncm. The modified
      stepped osteotomy had a significantly greater mean IT than the conventional
      osteotomy, but no significant difference in ISQ was found between groups. Pearson
      correlations showed a significant positive correlation between IT in the control
      and test groups. Significant correlations were found between ISQ and HU in the
      test group. No other significant correlations between HU, IT, and ISQ were found.
      CONCLUSION: Within the limits of this cadaver study, the modified stepped
      osteotomy resulted in significantly greater implant stability in terms of IT than
      the conventional osteotomy in soft bone. Significant correlations were found
      between the IT produced in the modified stepped osteotomy and bone density. No
      significant correlations were found between IT and ISQ.

PMID- 25615916
TI  - Accuracy of two digital implant impression systems based on confocal microscopy
      with variations in customized software and clinical parameters.
AB  - PURPOSE: To evaluate the accuracy of two digital impression systems based on the
      same technology but different postprocessing correction modes of customized
      software, with consideration of several clinical parameters. MATERIALS AND
      METHODS: A maxillary master model with six implants located in the second molar,
      second premolar, and lateral incisor positions was fitted with six cylindrical
      scan bodies. Scan bodies were placed at different angulations or depths apical to
      the gingiva. Two experienced and two inexperienced operators performed scans with
      either 3D Progress (MHT) or ZFX Intrascan (Zimmer Dental). Five different
      distances between implants (scan bodies) were measured, yielding five data points
      per impression and 100 per impression system. Measurements made with a high
      accuracy three-dimensional coordinate measuring machine (CMM) of the master model
      acted as the true values. The values obtained from the digital impressions were
      subtracted from the CMM values to identify the deviations. The differences
      between experienced and inexperienced operators and implant angulation and depth
      were compared statistically. RESULTS: Experience of the operator, implant
      angulation, and implant depth were not associated with significant differences in
      deviation from the true values with both 3D Progress and ZFX Intrascan. Accuracy
      in the first scanned quadrant was significantly better with 3D Progress, but ZFX
      Intrascan presented better accuracy in the full arch. CONCLUSION: Neither of the
      two systems tested would be suitable for digital impression of multiple-implant
      prostheses. Because of the errors, further development of both systems is
      required.

PMID- 25615917
TI  - Efficacy of two site-development procedures for implants in the maxillary
      esthetic region: a systematic review.
AB  - PURPOSE: The purpose of this systematic review was to identify studies in which
      either orthodontic extrusion or bone grafting was used prior to single implant
      placement in the maxillary esthetic zone and to compare the biologic, functional,
      and esthetic outcomes of these two approaches. MATERIALS AND METHODS: An
      electronic MEDLINE search was conducted by three independent reviewers to
      identify English-language articles, published in dental journals between January
      1992 and August 2013, reporting on single-implant site development accomplished
      by orthodontic forced eruption of nonrestorable teeth or by bone grafting
      procedures. The search terms were categorized into four groups comprising a PICO
      (problem, intervention, comparison, outcome) question. Supplementary manual
      searches of published full-text articles and related reviews were also performed.
      RESULTS: The initial database search produced 301 relevant titles. After careful
      examination and discussion, 32 studies were selected for inclusion. No study
      directly comparing the two implant site-development methods was identified. The
      observation periods of the available studies were either short or not stated.
      CONCLUSION: There is a substantial lack of evidence to determine which method for
      implant site development is better. Definitive conclusions cannot be drawn, since
      no clinical trials have directly compared these two methods. All included studies
      reported separately on the two implant site-development methods and used
      different protocols. According to the literature reviewed, it seems that both
      methods of implant site development are effective and neither method is superior.
      Multicenter studies and randomized clinical trials should be performed to
      evaluate the efficacy of these two methods.

PMID- 25615918
TI  - Effects of implant diameter and prosthesis retention system on the reliability of
      single crowns.
AB  - PURPOSE: The probability of survival of implant-supported prostheses may be
      affected by the interplay between different implant diameters supporting screwed
      or cemented crowns. The purpose of this study was to investigate the effect of
      implant diameter and prosthesis retention system on the reliability and failure
      modes of single crowns. MATERIALS AND METHODS: Internal-hexagon implants were
      divided into six groups (n = 21 each) according to implant diameter (3.3, 4.0, or
      5.0 mm) and crown retention system (screwed or cemented). Abutments were torqued
      to the implants, and crowns were then fixed and subjected to step-stress
      accelerated life testing in water. Use-level probability Weibull curves and
      reliability for missions of 50,000 cycles at 100, 150, and 200 N were calculated.
      Failure analysis was performed. RESULTS: Cemented systems presented higher
      reliability than screwed ones, except between 3.3-mm-diameter cemented and
      screwed systems at a load of 100 or 150 N. Failure modes were restricted to the
      abutment screw and varied with implant diameter only in the cement-retained
      groups. CONCLUSION: Higher reliability was observed for cement-retained crowns
      and implants of larger diameter compared to screw-retained and smaller diameter.
      Failure modes differed between groups.

PMID- 25615919
TI  - Effect of implant divergence on the accuracy of definitive casts created from
      traditional and digital implant-level impressions: an in vitro comparative study.
AB  - PURPOSE: The purpose of this research was to compare the accuracy of definitive
      casts created with digital and conventional methods for implants with internal
      octagon connections placed parallel or at different angles (15, 30, or 45
      degrees). MATERIALS AND METHODS: Four customized epoxy resin master casts were
      fabricated with two-implant analogs placed in the posterior mandible with
      different degrees of divergence. For the conventional (control) group, 10
      traditional impressions were taken on each master cast with custom trays, open
      tray impression copings, and polyvinyl siloxane; definitive stone casts were
      poured with type IV dental stone. For the digital group, 10 digital impressions
      were taken on each master cast with two-piece scannable impression copings and an
      intraoral digital scanner; definitive milled polyurethane casts were fabricated
      by the manufacturer. All four master casts and 80 control and test casts were
      scanned and digitized, and the data sets were compared. Any deviations in
      measurements between the definitive and corresponding master casts were analyzed
      statistically. RESULTS: The amount of divergence between implants did not affect
      the accuracy of the stone casts created conventionally; however, it significantly
      affected the accuracy of the milled casts created digitally. A decreasing linear
      trend in deviations for both distance and angle measurements suggested that the
      digital technique was more accurate when the implants diverged more. At 0 and 15
      degrees of divergence, the digital method resulted in highly significantly less
      accurate definitive casts. At 30 and 45 degrees of divergence, however, the
      milled casts showed either no difference or marginal differences with casts
      created conventionally. CONCLUSION: The digital pathway produced less accurate
      definitive casts than the conventional pathway with the tested two-implant
      scenarios. To ensure passive fit of definitive prostheses, verification devices
      and casts may be used when materials are produced digitally.

PMID- 25615920
TI  - Influence of prosthesis type and retention mechanism on complications with fixed
      implant-supported prostheses: a systematic review applying multivariate analyses.
AB  - PURPOSE: To identify the influence of fixed prosthesis type on biologic and
      technical complication rates in the context of screw versus cement retention.
      Furthermore, a multivariate analysis was conducted to determine which factors,
      when considered together, influence the complication and failure rates of fixed
      implant-supported prostheses. MATERIALS AND METHODS: Electronic searches of
      MEDLINE (PubMed), EMBASE, and the Cochrane Library were conducted. Selected
      inclusion and exclusion criteria were used to limit the search. Data were
      analyzed statistically with simple and multivariate random-effects Poisson
      regressions. RESULTS: Seventy-three articles qualified for inclusion in the
      study. Screw-retained prostheses showed a tendency toward and significantly more
      technical complications than cemented prostheses with single crowns and fixed
      partial prostheses, respectively. Resin chipping and ceramic veneer chipping had
      high mean event rates, at 10.04 and 8.95 per 100 years, respectively, for full
      arch screwed prostheses. For "all fixed prostheses" (prosthesis type not reported
      or not known), significantly fewer biologic and technical complications were seen
      with screw retention. Multivariate analysis revealed a significantly greater
      incidence of technical complications with cemented prostheses. Full-arch
      prostheses, cantilevered prostheses, and "all fixed prostheses" had significantly
      higher complication rates than single crowns. A significantly greater incidence
      of technical and biologic complications was seen with cemented prostheses.
      CONCLUSION: Screw-retained fixed partial prostheses demonstrated a significantly
      higher rate of technical complications and screw-retained full-arch prostheses
      demonstrated a notably high rate of veneer chipping. When "all fixed prostheses"
      were considered, significantly higher rates of technical and biologic
      complications were seen for cement-retained prostheses. Multivariate Poisson
      regression analysis failed to show a significant difference between screw- and
      cement-retained prostheses with respect to the incidence of failure but
      demonstrated a higher rate of technical and biologic complications for cement
      retained prostheses. The incidence of technical complications was more dependent
      upon prosthesis and retention type than prosthesis or abutment material.

PMID- 25615922
TI  - Delayed expansion of the atrophic mandible by ultrasonic surgery: a clinical and
      histologic case series.
AB  - PURPOSE: Ridge expansion is used to widen narrow ridges with adequate height for
      implant placement. This human case series presents the clinical and histologic
      results of delayed expansion of mandibles by ultrasonic surgery. MATERIALS AND
      METHODS: Patients with residual alveolar ridge width between 2.3 and 4.1 mm in
      the coronal area of the posterior mandible were included in the study. First,
      four linear corticotomies were carried out by ultrasonic surgical device. Four
      weeks later, adequate bone expansion with a combination of scalpels, thin
      chisels, and threaded osteotomes that did not compromise cortical vascularization
      was performed, and two implants per ridge were inserted. Any gaps were filled
      with corticospongious porcine biomaterial. Three months after implant placement,
      healing caps were inserted, and bone cores were harvested from the regenerated
      areas for histologic analysis. Crestal width was recorded at each surgery.
      RESULTS: The postoperative course was uneventful in all 32 patients (64 implants)
      who took part in the study, and the implant success rate was 96.88% at 3 months.
      The mean increase in ridge width was 5.17 +/- 0.86 mm. The histologic specimens
      showed a mixture of new bone and particles of biomaterial, as well as newly
      formed bone. Histomorphometry demonstrated that 64% +/- 3.1% of the specimen was
      composed of newly formed bone, 8% +/- 0.8% was made up of marrow spaces, and 27%
      +/- 2.6% comprised the residual grafted biomaterial. CONCLUSION: This study
      showed that mandibular ridge expansion using a delayed split-crest technique by
      means of ultrasonic surgery and association with biomaterial led to good
      horizontal bone gain, with no fractures of the buccal plate, and a high implant
      success rate. The histologic specimens showed newly formed bone and good
      integration of the biomaterial.

PMID- 25615921
TI  - Outcome after placement of tantalum porous engineered dental implants in fresh
      extraction sockets: a canine study.
AB  - PURPOSE: This study evaluated the stability and histologic proof of
      osseoincorporation of Trabecular Metal (TM) dental implants, which feature a
      tantalum-based porous midsection. MATERIALS AND METHODS: A total of 48 TM
      implants (test group) and Tapered Screw-Vent implants (control group) were
      immediately placed bilaterally into mandibular extraction sockets in dogs.
      Resonance frequency analysis was performed at weeks 0, 2, 4, and 12 after implant
      placement. Histologic and histomorphometric evaluations of the implant interface
      were performed. RESULTS: Changes in mean implant stability quotients (ISQ)
      revealed no statistical differences between the test and control groups.
      Histologic analysis showed bone ingrowth into the porous tantalum structure of
      all test group implants. Histomorphometric analysis revealed an increased
      percentage of bone-to-implant contact between 4 and 8 weeks in both test and
      control groups. The porous sections of the test group exhibited significantly
      more new bone inside the pores at week 12 in comparison to weeks 2 and 4. No
      correlation was observed between ISQ and histomorphometric parameters.
      CONCLUSION: In a canine immediate extraction socket model, both test and control
      implants demonstrated comparable implant stability and bone-to-implant contact.
      Bone ingrowth was evident within the tantalum porous section of the test implants
      during the early healing.

PMID- 25615923
TI  - Asymptomatic chronic rhinosinusitis and osteitis in patients treated with
      multiple zygomatic implants: a long-term radiographic follow-up.
AB  - PURPOSE: The aim of this study was to investigate implant survival and the
      reactions of the bone and mucosa of the maxillary sinuses in patients treated
      with fixed dental prostheses supported by multiple zygomatic implants. MATERIALS
      AND METHODS: Between 2001 and 2007, patients with extensive resorption of the
      basal bone of the maxilla received multiple zygomatic implants without grafts. In
      2012, the maxillary sinuses were examined with cone beam computed tomography. Neo
      osteogenesis at the posterior wall of the sinus was considered to be a sign of
      osteitis and classified as mild (3 to 4 mm), moderate (4 to 5 mm), or severe (> 5
      mm). The maxillary ostium was examined and accessory ostia were registered. The
      sinus mucosa was evaluated according to the Lund-Mackay staging system, and the
      sinus was checked for fluid level and atelectasis. Patients reported any nasal-
      and sinus-related symptoms. RESULTS: Fourteen patients who had received 58
      zygomatic implants and 13 standard implants were examined. The mean follow-up was
      9.3 years, and the implant survival rates were 97% and 92% for zygomatic and
      standard implants, respectively. Osteitis was found in all but one patient and
      classified as severe in 17 of the 27 investigated sinuses. The infundibulum was
      obstructed in nine sinuses, and an accessory ostium was present in seven. The
      mucosa of the maxillary sinus showed signs of chronic rhinosinusitis in all but
      one patient. No fluid levels were observed. Atelectasis occurred in 15 sinuses.
      Twelve patients reported unaltered nasal and sinus status. CONCLUSION: Patients
      with extensive bone resorption in combination with voluminous maxillary sinuses
      and nasal cavities can experience long-term success with prostheses supported by
      multiple zygomatic implants. Asymptomatic chronic rhinosinusitis with osteitis
      and gradual collapse of the maxillary sinus cavity can be anticipated.

PMID- 25615924
TI  - Immediate loading of complete-arch fixed prostheses for edentulous maxillae after
      flapless guided implant placement: a 1-year prospective clinical study.
AB  - PURPOSE: The purpose of this study was to evaluate prospectively the clinical
      effectiveness of immediate loading of implants with complete-arch fixed
      prostheses in edentulous maxillae after the implants were placed with flapless
      guided surgery. MATERIALS AND METHODS: Patients with edentulous maxillae who
      visited a single dental clinic during the recruitment period (April 2011 to May
      2012) were selected by consecutive sampling and predetermined selection criteria.
      Four to six implants were placed in each patient with flapless guided surgery.
      The outcome measures were insertion torque, surgical time, postoperative pain
      (100-mm visual analog scale), marginal bone level change, implant survival, and
      oral health-related quality of life. Patients were followed for up to 1 year.
      RESULTS: Fifty patients received 290 implants. All implants were immediately
      loaded 2 hours after placement with prefabricated fixed provisional prostheses.
      Two patients dropped out of the study. Hence, analyses were conducted for 278
      implants in 48 patients (26 men, 22 women; mean age 56.0 +/- 8.3 years; age
      range, 34 to 74 years). The average insertion torque was 57.7 +/- 16.6 Ncm, the
      average surgical time was 22.9 +/- 4.7 minutes, and the average score for
      postoperative pain was 14.7 +/- 9.3. One year after immediate loading, the
      implant survival rate was 98.6%. Four implants showed mobility early after
      implant placement and were lost. Mean marginal bone level changes were -0.32 +/-
      0.43 mm. Scores on the Oral Health Impact Profile-54 (Japanese version) improved
      significantly after prosthetic treatment. CONCLUSION: The results of this study
      indicate that this treatment method for edentulous maxillae is predictable, with
      a high implant survival rate and a clinically reasonable improvement in oral
      health-related quality of life.

PMID- 25615925
TI  - Vertical bone augmentation using recombinant bone morphogenetic protein,
      mineralized bone allograft, and titanium mesh: a retrospective cone beam computed
      tomography study.
AB  - PURPOSE: This retrospective study evaluated the use of a composite graft of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) and particulate
      mineralized bone allograft protected by a titanium mesh for vertical bone
      augmentation. MATERIALS AND METHODS: A review of data on patients from four oral
      and maxillofacial surgery practices in the United States who required vertical
      augmentation prior to implant treatment was conducted. Vertical augmentation was
      accomplished with rhBMP-2 in an absorbable collagen sponge (ACS) carrier and
      particulate allograft. Cone beam computed tomography was used to measure vertical
      bone gains using this technique. RESULTS: Sixteen vertical ridge augmentation
      procedures were performed in 15 patients. The maximum vertical bone gains ranged
      from 4.4 to 16.3 mm. The average maximum vertical bone gain was 8.53 mm. The
      procedure allowed implant placement in all patients. Forty implants were inserted
      into the grafted ridges after a minimum of 6 months of healing. All implants
      integrated and were used for prosthetic support. CONCLUSION: This study suggests
      that rhBMP-2/ACS and particulate mineralized bone allograft protected by a
      titanium mesh offers favorable vertical bone gains to allow dental implant
      placement.

PMID- 25615926
TI  - Repair of critical-size bone defects using bone marrow stem cells or autogenous
      bone with or without collagen membrane: a histomorphometric study in rabbit
      calvaria.
AB  - PURPOSE: The aim of this study was to evaluate bone healing after the use of a
      xenograft scaffold enriched with bone marrow mesenchymal stem cells (BM-MSCs), an
      autogenous bone graft, or the scaffold without BM-MSCs. MATERIALS AND METHODS:
      Eighteen rabbits were used for this study; bilateral 12-mm-diameter defects were
      created in the animals' parietal bones. The bilateral defects were filled with a
      xenograft enriched with BM-MSCs (test group [TG]), with autogenous bone graft
      (positive control group [PCG]), or with a xenograft alone (negative control group
      [NCG]). In all groups, randomly, one defect was covered with a collagen membrane.
      The rabbits were sacrificed 8 weeks after surgery, and their parietal bones were
      harvested and analyzed histomorphometrically. RESULTS: Within the PCG and the
      NCG, the defects covered with the barrier membrane showed better bone healing. In
      the TG, the defects covered with the barrier membrane did not show better bone
      healing (intragroup comparisons by Wilcoxon and Friedman tests for paired data).
      TG showed percentage of mineralized tissue (MT) of 56.03% +/- 3.49% with membrane
      and 57.71% +/- 5.31% without membrane. PCG showed MT of 55.13% +/- 4.83% and
      49.69% +/- 3.81% with and without membrane, respectively, and NCG showed MT of
      26.77% +/- 7.29% and 19.67% +/- 2.66% with and without membrane, respectively.
      CONCLUSION: Both autogenous bone graft and a xenograft enriched with BM-MSCs were
      equally effective for bone reconstruction and better than the xenograft alone.
      The use of a barrier membrane seemed to have a synergistic effect on bone healing
      in PCG and NCG but not in TG.

PMID- 25615927
TI  - Guided bone regeneration of mandibles using chitosan scaffold seeded with
      characterized uncultured omental adipose-derived stromal vascular fraction: an
      animal study.
AB  - PURPOSE: The aim of this study was to assess the effect of characterized
      uncultured omental adipose-derived stromal vascular fraction (SVF) on bone
      regeneration in a circular mandibular bone defect. A chitosan scaffold was used
      to maintain the cells in situ. MATERIALS AND METHODS: Seventy-five healthy male
      white Wistar rats were randomized into three experimental groups. In the control
      group, a surgical bone defect was created in the body of the mandible. In the
      scaffold group, a chitosan scaffold was placed into the defect. In the
      scaffold/SVF group, a scaffold was implanted and seeded with 10-MUL SVF aliquots
      (2.19 +/- 0.43 x 10(7) cells). RESULTS: Microscopic and histomorphometric
      analyses showed improved and earlier regeneration of bone defects in the
      scaffold/SVF group compared to the scaffold-only group. CONCLUSION: In this
      animal model, the use of a chitosan scaffold with SVF aliquots resulted in
      significantly earlier regeneration of bone than the use of the scaffold alone.

PMID- 25615928
TI  - Management of a complication with a fractured zirconia implant abutment in the
      esthetic zone.
AB  - Technical complications in implant prosthetic cases represent a major challenge
      in dentistry. This case report describes minimally invasive management to recover
      an implant with a fractured remnant of a zirconia abutment, including provisional
      rehabilitation during a sequential treatment protocol in the esthetic zone. A
      patient was treated with a screw-retained one-piece implant-supported
      reconstruction made of a customized zirconia abutment with direct ceramic
      veneering in the maxillary right central incisor position. During the prosthetic
      try-in, a fracture in the apical portion of the abutment was evident. The first
      rescue attempt led to fracture of the retrieval instrument. Immediately, an
      individualized wired construction was applied to bond the existing fractured
      reconstruction to the neighboring teeth to maintain the peri-implant mucosal
      architecture. Because the implant screw canal was blocked, a customized round bur
      had to be manufactured and was placed in the implant axis with a specific bracket
      tool from the service set to protect the interior implant threads. Then, the
      drills of the service set were guided by the newly created access to remove the
      fractured remnants. The implant screw was retapped and the area rinsed with
      chlorhexidine solution. All remnants were removed without the need for surgical
      intervention. Neither the implant connection nor the bone-to-implant interface
      was damaged. The stepwise treatment approach with the customized round bur
      combined with the system-specific drills of the service set saved the blocked
      implant so that the patient could be successfully rehabilitated with a new
      implant reconstruction. 

PMID- 25615929
TI  - Effects of morphology and chemical doping on electrochemical properties of metal
      hydroxides in pseudocapacitors.
AB  - It is well known that both the structural morphology and chemical doping are
      important factors that affect the properties of metal hydroxide materials in
      electrochemical energy storage devices. In this work, an effective method to
      tailor the morphology and chemical doping of metal hydroxides is developed. It is
      shown that the morphology and the degree of crystallinity of Ni(OH)2 can be
      changed by adding glucose in the ethanol-mediated solvothermal synthesis. Ni(OH)2
      produced in this manner exhibited an increased specific capacitance, which is
      partially attributed to its increased surface area. Interestingly, the effect of
      morphology on cobalt doped-Ni(OH)2 is found to be more effective at low cobalt
      contents than at high cobalt contents in terms of improving the electrochemical
      performance. This result reveals the existence of competitive effects between
      chemical doping and morphology change. These findings will provide important
      insights to design effective materials for energy storage devices. 

PMID- 25615930
TI  - Automated detection of actinic keratoses in clinical photographs.
AB  - BACKGROUND: Clinical diagnosis of actinic keratosis is known to have intra- and
      inter-observer variability, and there is currently no non-invasive and objective
      measure to diagnose these lesions. OBJECTIVE: The aim of this pilot study was to
      determine if automatically detecting and circumscribing actinic keratoses in
      clinical photographs is feasible. METHODS: Photographs of the face and dorsal
      forearms were acquired in 20 volunteers from two groups: the first with at least
      on actinic keratosis present on the face and each arm, the second with no actinic
      keratoses. The photographs were automatically analysed using colour space
      transforms and morphological features to detect erythema. The automated output
      was compared with a senior consultant dermatologist's assessment of the
      photographs, including the intra-observer variability. Performance was assessed
      by the correlation between total lesions detected by automated method and
      dermatologist, and whether the individual lesions detected were in the same
      location as the dermatologist identified lesions. Additionally, the ability to
      limit false positives was assessed by automatic assessment of the photographs
      from the no actinic keratosis group in comparison to the high actinic keratosis
      group. RESULTS: The correlation between the automatic and dermatologist counts
      was 0.62 on the face and 0.51 on the arms, compared to the dermatologist's intra
      observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic
      detection was 39.5% on the face, 53.1% on the arms. Positive predictive values
      were 13.9% on the face and 39.8% on the arms. Significantly more lesions
      (p<0.0001) were detected in the high actinic keratosis group compared to the no
      actinic keratosis group. CONCLUSIONS: The proposed method was inferior to
      assessment by the dermatologist in terms of sensitivity and positive predictive
      value. However, this pilot study used only a single simple feature and was still
      able to achieve sensitivity of detection of 53.1% on the arms.This suggests that
      image analysis is a feasible avenue of investigation for overcoming variability
      in clinical assessment. Future studies should focus on more sophisticated
      features to improve sensitivity for actinic keratoses without erythema and limit
      false positives associated with the anatomical structures on the face.

PMID- 25615931
TI  - The influence of diet on the gut microbiota and its consequences for health.
AB  - Man is an intimate symbiosis between 10 trillion human cells and some 100
      trillion bacteria, most of which inhabit the intestine where they constitute an
      extremely dense and diverse microbiota. This symbiotic balance that has to be
      established within each newborn is key to the maintenance of health and well
      being. Its development is markedly influenced by microbial exposure encountered
      very early in life. Mode of infant feeding, and the post-weaning transition to
      habitual diet will further shape the microbiota. Recent studies support the
      concept that diet should be viewed as a means to prevent potentially durable
      alterations of symbiosis observed in immune-mediated metabolic and inflammatory
      diseases. Non-digestible dietary fiber will play a major role in this context. 

PMID- 25615932
TI  - Controlled activation of retrotransposition for plant breeding.
AB  - Plant genomes consist to a large extent of transposable elements (TEs),
      predominantly retrotransposons. Their accumulation through periodic transposition
      bursts has shaped the structure and regulatory organization of plant genomes,
      often contributing to phenotypic traits. Transposon-generated phenotypes selected
      by humans during plant domestication have been maintained under strict selection
      during subsequent plant breeding. Our knowledge of the epigenetic, environmental,
      and developmental regulation of TE activity has advanced considerably in recent
      years. Here I will consider TEs as an attractive endogenous source of genetic
      variation that can be liberated in a controlled fashion and thus offer novel
      phenotypic diversity to be selected for crop improvement. 

PMID- 25615933
TI  - Mycophenolate-based graft versus host disease prophylaxis is not inferior to
      methotrexate in myeloablative-related donor stem cell transplantation.
AB  - We retrospectively reviewed 242 patients who received related donor myeloablative
      peripheral blood hematopoietic cell transplantation. We compared patients who
      received mycophenolate (MMF)/cyclosporine (CSA) (n = 71), to historical controls
      who received methotrexate (MTX)/CSA (n = 172). There were no differences in
      overall survival, nonrelapse mortality, and relapse. The MMF/CSA group had
      significantly faster neutrophil and platelet engraftment: medians of 13 versus 18
      days and 10 versus 14 days, respectively (P = 0.001). The cumulative incidence of
      acute graft versus host disease (GVHD) (Grades, 2-4) was significantly lower in
      the MMF/CSA group (45.1 vs. 74.4%, P < 0.001). The MMF/CSA group showed a lower
      incidence of skin (51.5 vs. 72.1%, P < 0.001) and liver acute GVHD (11.3 vs.
      54.2%, P < 0.001) and a higher incidence of lung (42.2 vs. 19.0%, P = 0.045), eye
      (59.7 vs. 30.1%, P < 0.001), and mouth (72.8 vs. 56.4%, P = 0.001) chronic GVHD
      but only eye chronic GVHD was confirmed in propensity score matching (PSM)
      analysis. The incidence of cytomegalovirus (CMV) viremia was higher in the
      MMF/CSA group (55.8 vs. 39.6%, P < 0.001) but this was not confirmed in PSM
      analysis. MMF/CSA was identified as an independent favorable factor for acute
      GVHD (P < 0.001, hazard ratio, 0.41) but as a possible adverse risk factor for
      CMV viremia as this was not found to be statistically significant in PSM
      analysis. MMF/CSA in myeloablative matched related donor peripheral blood stem
      cell transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA
      and is associated with faster engraftment but a potentially higher risk of CMV
      viremia.

PMID- 25615934
TI  - Serous ovarian, fallopian tube and primary peritoneal cancers: a common disease
      or separate entities - a systematic review.
AB  - OBJECTIVE: The aim of this systematic review is to analyze data on risk factors,
      epidemiology, clinicopathology and molecular biology from studies comparing
      primary peritoneal cancer, fallopian tube cancer and ovarian cancer of serous
      histology, in order to achieve a greater understanding of whether or not these
      disorders should be considered as separate entities. METHODS: A systematic
      literature search was conducted in PubMed and MEDLINE. Case-control studies
      comparing primary serous peritoneal or fallopian tube carcinomas with primary
      serous ovarian carcinomas or a control group were included. RESULTS: Twenty-eight
      studies were found eligible. Primary peritoneal cancer patients were older, had
      higher parity, were more often obese and had poorer survival compared to ovarian
      cancer patients. Differences in protein expression patterns of Her2/neu, estrogen
      and progestin receptors and frequency of loss of heterozygosity differed between
      primary peritoneal cancer and primary ovarian cancer patients. No major
      differences were found between primary fallopian tube cancer and primary ovarian
      cancer. The proportion of serous tubal intraepithelial carcinomas (STIC) was
      lower in primary peritoneal cancer and primary ovarian cancer compared to primary
      fallopian tube cancer. CONCLUSION: Except from differences in the proportion of
      STIC only few differences between primary fallopian tube cancer and primary
      ovarian cancer have been found. In contrast, observed differences in risk factor
      profile, clinicopathologic and prognostic factors, as well as in the molecular
      patterns, indicate that peritoneal cancer and ovarian cancer may be linked to
      different carcinogenic pathways.

PMID- 25615935
TI  - Correction: Comparison of Clinical Manifestations and Outcomes between Hepatitis
      B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma: Analysis of a
      Nationwide Cohort.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0112184.]. 

PMID- 25615937
TI  - 'Pharmacy of the World' is ill?

PMID- 25615936
TI  - Whole-transcriptome survey of the putative ATP-binding cassette (ABC) transporter
      family genes in the latex-producing laticifers of Hevea brasiliensis.
AB  - The ATP-binding cassette (ABC) proteins or transporters constitute a large
      protein family in plants and are involved in many different cellular functions
      and processes, including solute transportation, channel regulation and molecular
      switches, etc. Through transcriptome sequencing, a transcriptome-wide survey and
      expression analysis of the ABC protein genes were carried out using the
      laticiferous latex from Hevea brasiliensis (rubber tree). A total of 46 putative
      ABC family proteins were identified in the H. brasiliensis latex. These consisted
      of 12 'full-size', 21 'half-size' and 13 other putative ABC proteins, and all of
      them showed strong conservation with their Arabidopsis thaliana counterparts.
      This study indicated that all eight plant ABC protein paralog subfamilies were
      identified in the H. brasiliensis latex, of which ABCB, ABCG and ABCI were the
      most abundant. Real-time quantitative reverse transcription-polymerase chain
      reaction assays demonstrated that gene expression of several latex ABC proteins
      was regulated by ethylene, jasmonic acid or bark tapping (a wound stress)
      stimulation, and that HbABCB15, HbABCB19, HbABCD1 and HbABCG21 responded most
      significantly of all to the abiotic stresses. The identification and expression
      analysis of the latex ABC family proteins could facilitate further investigation
      into their physiological involvement in latex metabolism and rubber biosynthesis
      by H. brasiliensis. 

PMID- 25615938
TI  - F pocket flexibility influences the tapasin dependence of two differentially
      disease-associated MHC Class I proteins.
AB  - The human MHC class I protein HLA-B*27:05 is statistically associated with
      ankylosing spondylitis, unlike HLA-B*27:09, which differs in a single amino acid
      in the F pocket of the peptide-binding groove. To understand how this unique
      amino acid difference leads to a different behavior of the proteins in the cell,
      we have investigated the conformational stability of both proteins using a
      combination of in silico and experimental approaches. Here, we show that the
      binding site of B*27:05 is conformationally disordered in the absence of peptide
      due to a charge repulsion at the bottom of the F pocket. In agreement with this,
      B*27:05 requires the chaperone protein tapasin to a greater extent than the
      conformationally stable B*27:09 in order to remain structured and to bind
      peptide. Taken together, our data demonstrate a method to predict tapasin
      dependence and physiological behavior from the sequence and crystal structure of
      a particular class I allotype. Also watch the Video Abstract. 

PMID- 25615939
TI  - Incidence and prognosis of systemic lupus erythematosus in a 35 year period in
      Fukushima, Japan.
AB  - BACKGROUND: We examined the epidemiology, clinical manifestations, and prognosis
      of pediatric systemic lupus erythematosus (SLE) in Fukushima Prefecture, Japan
      over a 35 year period. METHODS: We collected the medical records of 37 patients
      diagnosed with SLE between 1977 and 2013. These children were divided into two
      groups. group 1 consisted of 19 patients who were diagnosed between 1977 and
      1995, and group 2 consisted of 18 patients diagnosed between 1996 and 2013. The
      epidemiology, clinical features, and prognosis were retrospectively compared
      between the two groups. RESULTS: The mean number of patients per 100,000 children
      per year for group 1 and group 2 was 0.33 +/- 0.25 and 0.35 +/- 0.30,
      respectively. The duration from onset of symptoms to treatment in group 2 was
      shorter than that in group 1, but the clinical and laboratory findings at onset
      did not differ between the two groups. All patients were treated with
      prednisolone, and 17 patients in group 1 and 18 in group 2 were treated with
      methylprednisolone pulse therapy. The frequency of cyclophosphamide treatment
      decreased whereas the frequency of cyclosporine, tacrolimus and mizoribine pulse
      therapy increased in group 2. SLE disease activity index (SLEDAI) score at the
      latest follow up in group 2 was lower in group 1. The survival rate was 84% in
      group 1 and 100% in group 2. CONCLUSION: The frequency and severity of SLE in
      group 1 were similar to those in group 2, and the prognosis of SLE in group 2 was
      better than that in group 1.

PMID- 25615940
TI  - Visual aggregate analysis of eligibility features of clinical trials.
AB  - OBJECTIVE: To develop a method for profiling the collective populations targeted
      for recruitment by multiple clinical studies addressing the same medical
      condition using one eligibility feature each time. METHODS: Using a previously
      published database COMPACT as the backend, we designed a scalable method for
      visual aggregate analysis of clinical trial eligibility features. This method
      consists of four modules for eligibility feature frequency analysis, query
      builder, distribution analysis, and visualization, respectively. This method is
      capable of analyzing (1) frequently used qualitative and quantitative features
      for recruiting subjects for a selected medical condition, (2) distribution of
      study enrollment on consecutive value points or value intervals of each
      quantitative feature, and (3) distribution of studies on the boundary values,
      permissible value ranges, and value range widths of each feature. All analysis
      results were visualized using Google Charts API. Five recruited potential users
      assessed the usefulness of this method for identifying common patterns in any
      selected eligibility feature for clinical trial participant selection. RESULTS:
      We implemented this method as a Web-based analytical system called VITTA (Visual
      Analysis Tool of Clinical Study Target Populations). We illustrated the
      functionality of VITTA using two sample queries involving quantitative features
      BMI and HbA1c for conditions "hypertension" and "Type 2 diabetes", respectively.
      The recruited potential users rated the user-perceived usefulness of VITTA with
      an average score of 86.4/100. CONCLUSIONS: We contributed a novel aggregate
      analysis method to enable the interrogation of common patterns in quantitative
      eligibility criteria and the collective target populations of multiple related
      clinical studies. A larger-scale study is warranted to formally assess the
      usefulness of VITTA among clinical investigators and sponsors in various
      therapeutic areas.

PMID- 25615941
TI  - Long-term treatment of clonidine, atenolol, amlodipine and dihydrochlorothiazide,
      but not enalapril, impairs the sexual function in male spontaneously hypertensive
      rats.
AB  - This study was designed to investigate the impact of representative
      antihypertensive drugs of 5 classes on the sexual function in male spontaneously
      hypertensive rats (SHR) at doses that achieved similar blood pressure (BP)
      reduction. The experiment was performed in 6 groups of male SHR. The dose are 20
      MUg/kg/day for clonidine, 3 mg/kg/day for enalapril, 20 mg/kg/day for atenolol, 2
      mg/kg/day for amlodipine, and 10 mg/kg/day for dihydrochlorothiazide. SHR were
      treated for 3 months, and then the penile erection and sexual behavior were
      detected. After BP recording, SHR were killed to evaluate the organ-damage,
      weight of accessory sex organs and levels of follicle-stimulating hormone (FSH),
      luteinizing hormone (LH) and testosterone in serum. Five drugs had the similar
      efficacy on BP reduction. All drugs except of enalapril, significantly prolonged
      the mount latency, and decreased the mount frequency (P<0.05). Clonidine also
      reduced the conception rate (45% vs. 80% in control group, P<0.05). Amlodipine
      and dihydrochlorothiazide significantly increased the testosterone level (0.79+/
      0.30, 0.80+/-0.34 vs. 0.49+/-0.20 in control group, unit: ng/dl, P<0.05).
      Enalapril, atenolol and amlodipine also significantly decreased the BP
      variability (systolic, 8.2+/-2.5, 7.6+/-1.8, 8.9+/-2.0 vs. 12.2+/-3.8 in control
      group, unit: mm Hg). All these drugs significantly decreased the organ-damage
      (P<0.05). In conclusion, long-term treatment with 5 common antihypertensive drugs
      possessed obvious organ protection in SHR. Clonidine, atenolol, amlodipine and
      dihydrochlorothiazide, but not enalapril, impair sexual function. 

PMID- 25615943
TI  - WITHDRAWN: Plant science with relevance to biotechnology.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, http://dx.doi.org/<10.1016/S0168
      1656(14)00098-4>. The duplicate article has therefore been withdrawn.

PMID- 25615942
TI  - Epidermal growth factor containing culture supernatant enhances intestine
      development of early-weaned pigs in vivo: potential mechanisms involved.
AB  - We have previously generated epidermal factor expressing Lactococcus lactis (EGF
      LL) using a bioengineering approach, and shown that EGF-LL fermentation
      supernatant enhanced newly weaned pigs growth. The objective of the current study
      was to further understand the mechanisms behind this improved performance. Sixty
      four piglets were weaned at 3 weeks of age and then fed ad libitum according to a
      2-phase feeding program. Four pens with 8 pigs per pen were assigned to each of
      two treatments for 3 weeks: (1) EGF containing supernatant from EGF-LL culture
      (SuperEGF) or (2) blank M17GE media (Control). Consistent with previous findings,
      SuperEGF pigs had an increased average daily gain during week 3 post-weaning
      (433.4 +/- 10.86 vs 388.7 +/- 7.76 g; P<0.05) and overall gain:feed ratio (0.757
      +/- 0.03 vs 0.677 +/- 0.01 kg/kg, P < 0.05). Moreover, jejunal structure
      development was enhanced, and inflammation index was minimized in SuperEGF pigs
      as indicated by increased villi height (P<0.05), decreased lamina propria width
      (P<0.05), and higher expression of anti-inflammatory cytokine, IL-13 (P<0.05).
      Further, goblet cell numbers and Muc2 levels were increased in SuperEGF pigs.
      Interestingly, the weaning-induced decrease of glucose cotransporter sodium
      glucose linked transporter 1 (SGLT1) and glucagon-like peptide-2 (GLP2) levels
      was reversed by SuperEGF supplementation. Our findings add to our understanding
      of the mechanisms behind enhancing piglet performance by EGF containing
      fermentation product.

PMID- 25615944
TI  - Enhancement of stability of L-tryptophan dehydrogenase from Nostoc punctiforme
      ATCC29133 and its application to L-tryptophan assay.
AB  - Microbial NAD(+)-dependent L-tryptophan dehydrogenase (TrpDH, EC1.4.1.19), which
      catalyzes the reversible oxidative deamination and the reductive amination
      between L-tryptophan and indole-3-pyruvic acid, was found in the scytonemin
      biosynthetic pathway of Nostoc punctiforme ATCC29133. The TrpDH exhibited high
      specificity toward L-tryptophan, but its instability was a drawback for L
      tryptophan determination. The mutant enzyme TrpDH L59F/D168G/A234D/I296N with
      thermal stability was obtained by screening of Escherichia coli transformants
      harboring various mutant genes, which were generated by error-prone PCR using
      complementation in an L-tryptophan auxotroph of E. coli. The specific activity
      and stability of this mutant enzyme were higher than those of the wild type
      enzyme. We also revealed here that in these four mutation points, the two amino
      acid residues Asp168 and Ile296 contributed to increase the enzyme stability, and
      the Leu59, Ala234 residues to increase its specific activity. Growth of the
      strain harboring the gene of above 4 point mutated enzyme was accelerated by the
      enhanced performance. In the present study, we demonstrated that TrpDH
      L59F/D168G/A234D/I296N was available for determination of L-tryptophan in human
      plasma.

PMID- 25615946
TI  - Production of chiral beta-amino acids using omega-transaminase from Burkholderia
      graminis.
AB  - Optically pure beta-amino acids are of high pharmacological significance since
      they are used as key ingredients in many physiologically active compounds.
      Despite a number of enzymatic routes to these compounds, an efficient synthesis
      of beta-amino acids continues to pose a major challenge for researchers. omega
      Transaminase has emerged as an important class of enzymes for generating amine
      compounds. However, only a few omega-transaminases have been reported so far
      which show activity towards aromatic beta-amino acids. In this study, (S)-omega
      transaminase from Burkholderia graminis C4D1M has been functionally characterized
      and used for the production of chiral aromatic beta-amino acids via kinetic
      resolution. The enzyme showed a specific activity of 3.1 U/mg towards rac-beta
      phenylalanine at 37 degrees C. The Km and Kcat values of this enzyme towards rac
      beta-phenylalanine with pyruvate as the amino acceptor were 2.88 mM and 91.57
      min(-1) respectively. Using this enzyme, racemic beta-amino acids were
      kinetically resolved to produce (R)-beta-amino acids with an excellent
      enantiomeric excess (> 99%) and ~ 50% conversion. Additionally, kinetic
      resolution of aromatic beta-amino acids was performed using benzaldehyde as a
      cheap amino acceptor.

PMID- 25615947
TI  - Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a
      combined human airway-tumour-stroma lung cancer model.
AB  - With more than 1 million deaths worldwide every year, lung cancer remains an area
      of unmet need. Accessible human in vitro 3D tissue models are required to improve
      preclinical predictivity. OncoCilAirTM is a new in vitro model of Non Small Cell
      Lung Cancer which combines a reconstituted human airway epithelium, human lung
      fibroblasts and lung adenocarcinoma cell lines. Remarkably, we found that in this
      3D microenvironment tumour cells expand by forming nodules, mimicking a human
      lung cancer feature. OncoCilAirTM mutated for KRAS and expressing the green
      fluorescent protein were used to test the antitumour potential of the
      investigational MEK inhibitors selumetinib and trametinib. As primary endpoint,
      changes in tumour size were assessed by fluorescence measurements. Tumours showed
      a reduced growth in response to the MEK inhibitors, but halting the selumetinib
      dosing resulted in tumour relapse. Importantly, toxicity study on the normal part
      of the cultures revealed that the airway epithelium integrity was also affected
      by anticancer drug treatments. These results highlight the possibility to assess
      simultaneously drug efficacy, drug side-effect and tumour recurrence within a
      single culture model. OncoCilAirTM heralds a new generation of integrated in
      vitro tumour models that should be valuable tools for drug development, while
      reducing animal testing. 

PMID- 25615945
TI  - Advanced targeted nanomedicine.
AB  - Targeted drug delivery has been the major topic in drug formulation and delivery.
      As nanomedicine emerges to create nano scale therapeutics and diagnostics, it is
      still essential to embed targeting capability to these novel systems to make them
      useful. Here we discuss various targeting approaches for delivery of therapeutic
      and diagnostic nano materials in view of search for more universal methods to
      target diseased tissues. Many diseases are accompanied with hypoxia and acidosis.
      Coating nanoparticles with pH Low Insertion Peptides (pHLIPs) increases
      efficiency of targeting acidic diseased tissues. It has been showing promising
      results to create future nanotheranostics for cancer and other diseases which are
      dominating in the present world. 

PMID- 25615948
TI  - Assessment by three-dimensional power Doppler ultrasound of cerebral blood flow
      perfusion in fetuses with congenital heart disease.
AB  - OBJECTIVES: To use three-dimensional (3D) power Doppler ultrasound to investigate
      cerebral blood flow perfusion in fetuses with congenital heart disease (CHD).
      METHODS: The vascularization index (VI), flow index (FI) and vascularization flow
      index (VFI) in the total intracranial volume and the main arterial territories
      (middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior
      cerebral artery (PCA)) were evaluated prospectively and compared in 112 fetuses
      with CHD and 112 normal fetuses using 3D power Doppler. Correlations between the
      3D power Doppler indices and neurodevelopment scores at 12 months of age were
      assessed in a subset of the CHD group, and values were compared with those of
      controls. RESULTS: Compared with the controls, the VI, FI and VFI of the total
      intracranial volume and the three main arteries were significantly higher in
      fetuses with hypoplastic left heart syndrome and left-sided obstructive lesions
      (P < 0.001), and the 3D power Doppler values in the ACA territory were
      significantly higher in fetuses with transposition of the great arteries (P <
      0.01). The largest proportional increase in the blood flow perfusion indices in
      the fetuses with CHD relative to controls was observed in the ACA territory (P <
      0.05). Among 41 cases with CHD that underwent testing, the mean Psychomotor
      Development Index (PDI) and Mental Development Index (MDI) scores were
      significantly lower than in 94 of the controls that were tested (P < 0.001).
      Among these CHD cases, total intracranial FI was positively correlated with PDI
      (r = 0.342, P = 0.029) and MDI (r = 0.339, P = 0.030), and ACA-VI and ACA-VFI
      were positively correlated with PDI (r = 0.377 and 0.389, P = 0.015 and 0.012,
      respectively) but were not correlated with MDI (r = 0.243 and 0.203, P = 0.126
      and 0.204, respectively). CONCLUSIONS: Cerebral blood flow perfusion was
      increased relative to controls in most fetuses with CHD and was associated with
      neurodevelopment scores at 12 months. Prenatal 3D power Doppler ultrasound might
      help to identify cases of brain vasodilatation earlier and inform parental
      counseling.

PMID- 25615949
TI  - Credibility and reproducibility.

PMID- 25615950
TI  - Antibacterial drug discovery: doing it right.
AB  - Antibacterial drug discovery needs to develop new strategies to identify
      attractive hit-target couples for more effective lead finding and optimization.
      In this issue of Chemistry & Biology, Park and coworkers describe a novel target
      based whole cell combination screening approach resulting in the identification
      of new inhibitors of biotin biosynthesis in Mycobacterium tuberculosis.

PMID- 25615951
TI  - Absence of a stable secondary structure is not a limitation for photoswitchable
      inhibitors of beta-arrestin/beta-Adaptin 2 protein-protein interaction.
AB  - Many protein-protein interactions (PPIs) are mediated by short, often helical,
      linear peptides. Molecules mimicking these peptides have been used to inhibit
      their PPIs. Recently, photoswitchable peptides with little secondary structure
      have been developed as modulators of clathrin-mediated endocytosis. Here we
      perform a systematic analysis of a series of azobenzene-crosslinked peptides
      based on a beta-arrestin P-long 20-mer peptide (BAP-long) sequence to assess the
      relevance of secondary structure in their interaction with beta-adaptin 2 and to
      identify the design requirements for photoswitchable inhibitors of PPI (PIPPIs).
      We observe that flexible structures show a greater inhibitory capacity and
      enhanced photoswitching ability and that the absence of helical structures in
      free inhibitor peptide is not a limitation for PIPPI candidates. Therefore, our
      PIPPIs expand the field of potential inhibitors of PPIs to the wide group of
      flexible peptides, and we argue against using a stable secondary structure as a
      sole criterion when designing PIPPI candidates. 

PMID- 25615952
TI  - Evaluation of the Wii Balance Board for walking aids prediction: proof-of-concept
      study in total knee arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: To provide proof-of-concept for the validity of the
      Wii Balance Board (WBB) measures to predict the type of walking aids required by
      inpatients with a recent (<=4 days) total knee arthroplasty (TKA). METHODS: A
      cross-sectional sample of 89 inpatients (mean age, 67.0+/-8 years) with TKA was
      analyzed. A multivariable proportional odds prediction model was constructed
      using 8 pre-specified predictors - namely, age, sex, body mass index, knee pain,
      knee range-of-motion, active knee lag, and WBB-derived standing balance. The type
      of walking aids prescribed on day 4 post-surgery was the outcome of interest - an
      ordinal variable with 4 categories (walking stick, narrow- and broad-base
      quadstick, and walking frame). RESULTS: Women, increasing body mass index, and
      poorer standing balance were independently associated with greater odds for
      requiring walking aids with a larger base-of-support. The concordance-index of
      the prediction model was 0.74. The model comprising only WBB-derived standing
      balance had nearly half (44%) the explanatory power of the full model. Adding WBB
      derived standing balance to conventional demographic and knee variables resulted
      in a continuous net reclassification index of 0.60 (95%CI,0.19-1.01),
      predominantly due to better identification of patients who required walking aids
      with a large base-of-support (sensitivity gain). CONCLUSIONS: The WBB was able to
      provide quantitative measures of standing balance which could assist healthcare
      professionals in prescribing the appropriate type of walking aids for patients.
      Further investigation is needed to assess whether using the WBB could lead to
      meaningful changes in clinical outcomes such as falls.

PMID- 25615954
TI  - Telemedicine in the Northern Territory: an assessment of patient perceptions in
      the preoperative anaesthetic clinic.
AB  - OBJECTIVE: We investigated patient perceptions of a virtual preoperative
      anaesthesia evaluation clinic linking Royal Darwin Hospital to Katherine
      Hospital. DESIGN: Descriptive study, cross-sectional survey. SETTING: Regional
      and rural areas of Northern Territory, Australia. PARTICIPANTS: Sample includes
      27 respondents, five Indigenous, 18 non-Indigenous and four unknown.
      INTERVENTIONS: Introduction of a preoperative anaesthesia evaluation clinic. MAIN
      OUTCOME MEASURES: We designed a 10-item, 5-point Likert scale questionnaire
      assessing patient perceptions in four domains: (i) technical quality; (ii)
      perceived efficacy; (iii) affective patient experience; and (iv) patient
      preference. Qualitative responses are also reported. RESULTS: Twenty-seven out of
      35 patients (77%) completed the questionnaire. Ninety-eight per cent were in
      positive agreement on technical quality with a mean score of 1.35 (SD: 0.53);
      Ninety-five per cent on perceived efficacy, 1.35 (SD: 0.65); Eighty-four per cent
      in negative agreement on affective patient experience (negative perception item),
      4.19 (SD: 1.07); Eighty-one per cent in negative agreement on patient preference
      (negative perception item), 4.23 (SD: 1.14). There were no significant
      differences in the answers between Indigenous (five patients) and non-Indigenous
      patients (18 patients). CONCLUSION: Our study confirms the acceptability of
      telemedicine in the remote assessment of preoperative patients in the Northern
      Territory, with positive perceptions in all four domains.

PMID- 25615955
TI  - Simple markers for subclinical inflammation in patients with Familial
      Mediterranean Fever.
AB  - BACKGROUND: In this study we investigated the potential of neutrophil/lymphocyte
      ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV), and red
      cell width distribution (RDW) as new inflammatory markers to identify chronic
      inflammations during symptom-free periods in children diagnosed with Familial
      Mediterranean Fever (FMF). MATERIAL/METHODS: The study included 153 children
      diagnosed with FMF based on the Tel-Hashomer Criteria, and 90 healthy volunteers.
      Hospital records were obtained to collect NLR, PLR, MPV, RDW, and FMF scores and
      the FMF mutation analyses of the patients enrolled in the study. Data on
      proteinuria were also collected and defined as a protein/creatinine ratio>0.2.
      RESULTS: NLR, PLR, MPV, and RDW were significantly higher in symptom-free FMF
      patients than in the control group. C-reactive protein values also weakly
      correlated with NLR, PLR, MPV, and RDW, but the correlation was not statistically
      significant. NLR had the strongest correlation with CRP. The NLR cut-off point to
      indicate subclinical inflammation in symptom-free FMF patients was calculated to
      be 1.65. CONCLUSIONS: NLR, PLR, MPV, and RDW are potential subclinical
      inflammation markers in patients with FMF. NLR, PLR, MPV, and RDW values are
      higher in patients with FMF during symptom-free periods. NLR was found to be the
      most reliable marker for subclinical inflammation when compared to PLR, MPV, and
      RDW. We also found that these markers are not significantly higher in proteinuric
      patients when compared with levels in non-proteinuric patients.

PMID- 25615956
TI  - No association between vitamin D levels and inflammation markers in patients with
      acute coronary syndrome.
AB  - PURPOSE: A modern concept regards acute coronary syndrome (ACS) as an auto
      inflammatory disorder. The purpose of the present study is to assess the plasma
      levels of inflammation related to biomarkers and cytokines in ACS patients and to
      correlate the values with 25-hydroxy vitamin D3 (calcidiol). There are no
      previously published reports concerning serum concentrations of inflammatory
      markers in patients with hypovitaminosis D in ACS. PATIENTS AND METHODS: Eighty
      eight consecutive patients with ACS [n=47 ST elevation myocardial infarction
      (STEMI), n=41 unstable angina pectoris (USAP)] were enrolled within 12h after
      symptoms. The blood samples were collected on admission in order to evaluate
      calcidiol, serum amyloid A (SAA), interleukin (IL)-6, interleukin (IL)-10, tumor
      necrosis factor-alpha (TNFalpha) and high sensitivity C-reactive protein (hsCRP).
      RESULTS: Calcidiol, TNFalpha and SAA levels were significantly lower (p=0.01,
      p<0.01 and p<0.01 respectively), whereas hsCRP levels were significantly higher
      (p<0.01) in STEMI group as compared to USAP group. In the STEMI group, there were
      negative correlations between SAA and hsCRP (r=-0.347; p=0.01) and SAA and IL-6
      (r=-0.356; p=0.01). There was a positive correlation between IL-6 and hsCRP
      (r=0.529; p<0.01). In the USAP group, it was found that there were a strong
      negative correlation between SAA and hsCRP (r=-0.75; p<0.01) and a positive
      correlation between IL-6 and TNF-alpha (r=0.54; p<0.01). CONCLUSION: This study
      demonstrates that calcidiol levels are not associated with the inflammation
      markers in patients with acute phase ACS.

PMID- 25615958
TI  - Synthesis and structural characterization of 3,5-dinitro-1,2,4-triazolates.
AB  - Salts of 3,5-dinitro-1H-1,2,4-triazole, a building block for energetic materials,
      have been prepared and fully characterized. Most of the studied salts exhibit
      high thermal stability and very low shock and friction sensitivities. 3,5-Dinitro
      1,2,4-triazolates with the nitrogen-rich ammonium, guanidinium, aminoguanidinium,
      and aminotetrazolium cations are energetic and have potential for energetic
      material applications. Salts containing alkali, alkali earth metal, and silver
      cations exhibit coloured emissions upon combustion while salts with large organic
      cations such as PPh4(+) and (Ph3P)2N(+) are highly insensitive and can be easily
      crystallized. 

PMID- 25615957
TI  - Response to 'perineal hernia formation following extralevator abdominoperineal
      excision'.

PMID- 25615959
TI  - Interleukin-6 and tumor necrosis factor-alpha are associated with quality of life
      related symptoms in pulmonary arterial hypertension.
AB  - RATIONALE: Inflammation is associated with symptoms in many chronic illnesses;
      however, this link has not been established in pulmonary arterial hypertension.
      OBJECTIVES: The objective of this study was to investigate the association
      between inflammatory markers and quality of life-related symptoms in patients
      with pulmonary arterial hypertension. We hypothesized that higher circulating IL
      6 and tumor necrosis factor-alpha levels would be associated with worse quality
      of life-related symptoms. METHODS: We performed a secondary analysis using
      baseline and 3-month assessments of 62 subjects in a clinical trial of aspirin
      and simvastatin to determine the association between plasma IL-6 and tumor
      necrosis factor-alpha levels and the Medical Outcomes Study Short Form-36
      subscales (pain, vitality, mental health). MEASUREMENTS AND MAIN RESULTS: The
      mean age was 49.7+/-13.4 years; 87% were female. Higher IL-6 levels were
      significantly associated with lower Medical Outcomes Study Short Form-36 subscale
      scores, indicating worse bodily pain, vitality, and mental health (all P<0.01).
      Higher tumor necrosis factor-alpha levels were significantly associated with
      increased bodily pain, but better mental health scores. CONCLUSIONS: IL-6 and
      tumor necrosis factor-alpha levels are associated with certain quality of life
      domains in patients with pulmonary arterial hypertension. Clinical trial
      registered with www.clinicaltrials.gov (NCT00384865).

PMID- 25615962
TI  - Zinc-substituted pseudoazurin solved by S/Zn-SAD phasing.
AB  - The copper(II) centre of the blue copper protein pseudoazurin from Alcaligenes
      faecalis has been substituted by zinc(II) via denaturing the protein, chelation
      and removal of copper and refolding the apoprotein, followed by the addition of
      an aqueous solution of ZnCl2. Vapour-diffusion experiments produced colourless
      hexagonal crystals (space group P65), which when cryocooled had unit-cell
      parameters a=b=49.01, c=98.08 A. Diffraction data collected at 100 K using a
      copper sealed tube were phased by the weak anomalous signal of five S atoms and
      one Zn atom. The structure was fitted manually and refined to 1.6 A resolution.
      The zinc-substituted protein exhibits similar overall geometry to the native
      structure with copper. Zn2+ binds more strongly to its four ligand atoms (His40
      Ndelta1, Cys78 Sgamma, His81 Ndelta1 and Met86 Sdelta) and retains the
      tetrahedral arrangement, although the structure is less distorted than the native
      copper protein.

PMID- 25615961
TI  - A comprehensive review of the lipid cubic phase or in meso method for
      crystallizing membrane and soluble proteins and complexes.
AB  - The lipid cubic phase or in meso method is a robust approach for crystallizing
      membrane proteins for structure determination. The uptake of the method is such
      that it is experiencing what can only be described as explosive growth. This
      timely, comprehensive and up-to-date review introduces the reader to the practice
      of in meso crystallogenesis, to the associated challenges and to their solutions.
      A model of how crystallization comes about mechanistically is presented for a
      more rational approach to crystallization. The possible involvement of the
      lamellar and inverted hexagonal phases in crystallogenesis and the application of
      the method to water-soluble, monotopic and lipid-anchored proteins are addressed.
      How to set up trials manually and automatically with a robot is introduced with
      reference to open-access online videos that provide a practical guide to all
      aspects of the method. These range from protein reconstitution to crystal
      harvesting from the hosting mesophase, which is noted for its viscosity and
      stickiness. The sponge phase, as an alternative medium in which to perform
      crystallization, is described. The compatibility of the method with additive
      lipids, detergents, precipitant-screen components and materials carried along
      with the protein such as denaturants and reducing agents is considered. The
      powerful host and additive lipid-screening strategies are described along with
      how samples that have low protein concentration and cell-free expressed protein
      can be used. Assaying the protein reconstituted in the bilayer of the cubic phase
      for function is an important element of quality control and is detailed. Host
      lipid design for crystallization at low temperatures and for large proteins and
      complexes is outlined. Experimental phasing by heavy-atom derivatization, soaking
      or co-crystallization is routine and the approaches that have been implemented to
      date are described. An overview and a breakdown by family and function of the
      close to 200 published structures that have been obtained using in meso-grown
      crystals are given. Recommendations for conducting the screening process to give
      a more productive outcome are summarized. The fact that the in meso method also
      works with soluble proteins should not be overlooked. Recent applications of the
      method for in situ serial crystallography at X-ray free-electron lasers and
      synchrotrons are described. The review ends with a view to the future and to the
      bright prospects for the method, which continues to contribute to our
      understanding of the molecular mechanisms of some of nature's most valued
      proteinaceous robots. 

PMID- 25615963
TI  - Expression, purification, crystallization and preliminary X-ray crystallographic
      analysis of the histone-like HU protein from Spiroplasma melliferum KC3.
AB  - HU proteins belong to the nucleoid-associated proteins (NAPs) that are involved
      in vital processes such as DNA compaction and reparation, gene transcription etc.
      No data are available on the structures of HU proteins from mycoplasmas. To this
      end, the HU protein from the parasitic mycoplasma Spiroplasma melliferum KC3 was
      cloned, overexpressed in Escherichia coli and purified to homogeneity. Prismatic
      crystals of the protein were obtained by the vapour-diffusion technique at 4
      degrees C. The crystals diffracted to 1.36 A resolution (the best resolution ever
      obtained for a HU protein). The diffraction data were indexed in space group C2
      and the structure of the protein was solved by the molecular-replacement method
      with one monomer per asymmetric unit. 

PMID- 25615964
TI  - Protein purification, crystallization and preliminary X-ray diffraction analysis
      of L-arabinose isomerase from Lactobacillus fermentum CGMCC2921.
AB  - L-Arabinose isomerase (AI) catalyzes the isomerization of L-arabinose to L
      ribulose, as well as that of D-galactose to D-tagatose. A thermophilic AI derived
      from Lactobacillus fermentum CGMCC2921 (LFAI) was overexpressed in Escherichia
      coli BL21 (DE3). This enzyme was purified to over 95% purity by nickel affinity,
      Mono-Q ion-exchange and size-exclusion chromatography. The LFAI protein was
      crystallized from either 0.1 M bis-tris pH 6.5, 23% PEG 3350, 0.3 M NaCl (form 1
      crystals) or 0.1 M bis-tris pH 6.0, 25% PEG monomethyl ether 5000 (form 2
      crystals). Diffraction data from form 1 LFAI crystals were collected to 2.80 A
      resolution using synchrotron radiation. The form 1 crystals belonged to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a=85.11,
      b=184.57, c=186.26 A, alpha=beta=gamma=90 degrees . The asymmetric unit contained
      six LFAI subunits, corresponding to a calculated Matthews coefficient of 2.29 A3
      Da(-1) and a solvent content of 46.22%.

PMID- 25615965
TI  - Structures of Drosophila melanogaster Rab2 and Rab3 bound to GMPPNP.
AB  - Rab GTPases belong to the large family of Ras proteins. They act as key
      regulators of membrane organization and intracellular trafficking. Functionally,
      they act as switches. In the active GTP-bound form they can bind to effector
      proteins to facilitate the delivery of transport vesicles. Upon stimulation, the
      GTP is hydrolyzed and the Rab proteins undergo conformational changes in their
      switch regions. This study focuses on Rab2 and Rab3 from Drosophila melanogaster.
      Whereas Rab2 is involved in vesicle transport between the Golgi and the
      endoplasmatic reticulum, Rab3 is a key player in exocytosis, and in the synapse
      it is involved in the assembly of the presynaptic active zone. Here, high
      resolution crystal structures of Rab2 and Rab3 in complex with GMPPNP and Mg2+
      are presented. In the structure of Rab3 a modified cysteine residue is observed
      with an enigmatic electron density attached to its thiol function.

PMID- 25615966
TI  - Expression and crystallization of a bacterial glycoside hydrolase family 116 beta
      glucosidase from Thermoanaerobacterium xylanolyticum.
AB  - The Thermoanaerobacterium xylanolyticum gene product TxGH116, a glycoside
      hydrolase family 116 protein of 806 amino-acid residues sharing 37% amino-acid
      sequence identity over 783 residues with human glucosylceramidase 2 (GBA2), was
      expressed in Escherichia coli. Purification by heating, immobilized metal
      affinity and size-exclusion chromatography produced >90% pure TxGH116 protein
      with an apparent molecular mass of 90 kDa on SDS-PAGE. The purified TxGH116
      enzyme hydrolyzed the p-nitrophenyl (pNP) glycosides pNP-beta-D-glucoside, pNP
      beta-D-galactoside and pNP-N-acetyl-beta-D-glucopyranoside, as well as cellobiose
      and cellotriose. The TxGH116 protein was crystallized using a precipitant
      consisting of 0.6 M sodium citrate tribasic, 0.1 M Tris-HCl pH 7.0 by vapour
      diffusion with micro-seeding to form crystals with maximum dimensions of 120*25*5
      um. The TxGH116 crystals diffracted X-rays to 3.15 A resolution and belonged to
      the monoclinic space group P2(1). Structure solution will allow a structural
      explanation of the effects of human GBA2 mutations.

PMID- 25615967
TI  - Crystallization and preliminary crystallographic studies of a novel noncatalytic
      carbohydrate-binding module from the Ruminococcus flavefaciens cellulosome.
AB  - Microbial degradation of the plant cell wall is a fundamental biological process
      with considerable industrial importance. Hydrolysis of recalcitrant
      polysaccharides is orchestrated by a large repertoire of carbohydrate-active
      enzymes that display a modular architecture in which a catalytic domain is
      connected via linker sequences to one or more noncatalytic carbohydrate-binding
      modules (CBMs). CBMs direct the appended catalytic modules to their target
      substrates, thus potentiating catalysis. The genome of the most abundant ruminal
      cellulolytic bacterium, Ruminococcus flavefaciens strain FD-1, provides an
      opportunity to discover novel cellulosomal proteins involved in plant cell-wall
      deconstruction. It encodes a modular protein comprising a glycoside hydrolase
      family 9 catalytic module (GH9) linked to two unclassified tandemly repeated CBMs
      (termed CBM-Rf6A and CBM-Rf6B) and a C-terminal dockerin. The novel CBM-Rf6A from
      this protein has been crystallized and data were processed for the native and a
      selenomethionine derivative to 1.75 and 1.5 A resolution, respectively. The
      crystals belonged to orthorhombic and cubic space groups, respectively. The
      structure was solved by a single-wavelength anomalous dispersion experiment using
      the CCP4 program suite and SHELXC/D/E. 

PMID- 25615968
TI  - Purification, crystallization and preliminary crystallographic analysis of
      DR0248, an MNT-HEPN fused protein from Deinococcus radiodurans.
AB  - DR0248 is a protein identified in the Deinococcus radiodurans (DR) genome that is
      predicted to encompass two domains: an N-terminal minimal nucleotidyl transferase
      domain (MNT) and a C-terminal higher eukaryotes and prokaryotes nucleotide
      binding domain (HEPN). These two domains, usually encoded in two ORFs, have been
      suggested to play the role of a toxin-antitoxin (TA) system in prokaryotes.
      Recombinant DR0248 was overexpressed and purified from Escherichia coli and
      diffraction-quality crystals were obtained in the presence of the detergent
      molecules dodecyldimethylamine oxide (DDAO) and octaethylene glycol monododecyl
      ether (C12E8), which were used as crystallization additives. Crystals grown with
      DDAO diffracted to a resolution of 2.24 A and belonged to space group C222(1),
      with unit-cell parameters a=98.4, b=129.9, c=59.2 A. Crystals grown with C12E8
      diffracted to a resolution of 1.83 A and belonged to space group P2(1)2(1)2(1),
      with unit-cell parameters a=51.6, b=87.2, c=108.2 A. The structure was solved by
      multiwavelength anomalous dispersion from zinc bound to the protein using a
      single crystal obtained in the presence of DDAO.

PMID- 25615969
TI  - Overexpression, purification, crystallization and preliminary X-ray
      crystallographic analysis of SF173 from Shigella flexneri.
AB  - Shigella flexneri is a Gram-negative, anaerobic bacterium in the genus Shigella
      that can cause diarrhoea in humans. SF173, a hypothetical protein from S.
      flexneri 5a strain M90T, has been cloned, overexpressed, purified and
      crystallized as a part of laboratory-scale structural genomics project. The SF173
      protein was crystallized using the sitting-drop vapour-diffusion method in the
      presence of 0.8 M succinic acid pH 7.0 at 293 K. Preliminary X-ray diffraction
      analysis revealed that the crystal diffracted to 1.47 A resolution and belonged
      to space group I432, with unit-cell parameters a=b=c=110.245 A.

PMID- 25615970
TI  - Crystallization and preliminary X-ray analysis of the type IV restriction
      endonuclease ScoMcrA from Streptomyces coelicolor, which cleaves both Dcm
      methylated DNA and phosphorothioated DNA.
AB  - ScoMcrA is a type IV modification-dependent restriction endonuclease found in the
      model strain Streptomyces coelicolor. Unlike type I, II and III restriction
      endonucleases, which cleave unmodified DNA, type IV restriction endonucleases
      cleave modified DNA, including methylated, hydroxymethylated, glucosyl
      hydroxymethylated and phosphorothioated DNA. ScoMcrA targets both Dcm-methylated
      DNA and phosphorothioated DNA, and makes double-strand breaks 16-28 nt away from
      the modified nucleotides or the phosphorothioate links. However, the mechanism by
      which ScoMcrA recognizes these two entirely different types of modification
      remains unclear. In this study, the ScoMcrA protein was overexpressed, purified
      and crystallized. The crystals diffracted to 3.35 A resolution and belonged to
      space group P2(1)2(1)2(1). The unit-cell parameters were determined to be
      a=130.19, b=139.36, c=281.01 A, alpha=beta=gamma=90 degrees . These results will
      facilitate the detailed structural analysis of ScoMcrA and further elucidation of
      its biochemical mechanism.

PMID- 25615971
TI  - Expression, purification and crystallization of a membrane-associated,
      catalytically active type I signal peptidase from Staphylococcus aureus.
AB  - Staphylococcus aureus infections are becoming increasingly difficult to treat as
      they rapidly develop resistance to existing antibiotics. Bacterial type I signal
      peptidases are membrane-associated, cell-surface serine proteases with a unique
      catalytic mechanism that differs from that of eukaryotic endoplasmic reticulum
      signal peptidases. They are thus potential antimicrobial targets. S. aureus has a
      catalytically active type I signal peptidase, SpsB, that is essential for cell
      viability. To elucidate its structure, the spsB gene from S. aureus Newman strain
      was cloned and overexpressed in Escherichia coli. After exploring many different
      protein-modification constructs, SpsB was expressed as a fusion protein with
      maltose-binding protein and crystallized by hanging-drop vapour diffusion. The
      crystals belonged to the monoclinic space group P2(1) and diffracted to 2.05 A
      resolution. The crystal structure of SpsB is anticipated to provide structural
      insight into Gram-positive signal peptidases and to aid in the development of
      antibacterial agents that target type I signal peptidases.

PMID- 25615972
TI  - Three-dimensional structure of a variant 'Termamyl-like' Geobacillus
      stearothermophilus alpha-amylase at 1.9 A resolution.
AB  - The enzyme-catalysed degradation of starch is central to many industrial
      processes, including sugar manufacture and first-generation biofuels. Classical
      biotechnological platforms involve steam explosion of starch followed by the
      action of endo-acting glycoside hydrolases termed alpha-amylases and then exo
      acting alpha-glucosidases (glucoamylases) to yield glucose, which is subsequently
      processed. A key enzymatic player in this pipeline is the 'Termamyl' class of
      bacterial alpha-amylases and designed/evolved variants thereof. Here, the three
      dimensional structure of one such Termamyl alpha-amylase variant based upon the
      parent Geobacillus stearothermophilus alpha-amylase is presented. The structure
      has been solved at 1.9 A resolution, revealing the classical three-domain fold
      stabilized by Ca2+ and a Ca2+-Na+-Ca2+ triad. As expected, the structure is
      similar to the G. stearothermophilus alpha-amylase but with main-chain deviations
      of up to 3 A in some regions, reflecting both the mutations and differing crystal
      packing environments.

PMID- 25615973
TI  - Crystallization and preliminary X-ray analysis of the C-terminal fragment of
      PorM, a subunit of the Porphyromonas gingivalis type IX secretion system.
AB  - PorM is a membrane protein involved in the assembly of the type IX secretion
      system (T9SS) from Porphyromonas gingivalis, a major bacterial pathogen
      responsible for periodontal disease in humans. The periplasmic domain of PorM was
      overexpressed in Escherichia coli and purified. A fragment of the purified
      protein was obtained by limited proteolysis. Crystals of this fragment belonged
      to the tetragonal space group P4(3)2(1)2. Native and MAD data sets were recorded
      to 2.85 and 3.1 A resolution, respectively, using synchrotron radiation.

PMID- 25615974
TI  - Systematic analysis of protein-detergent complexes applying dynamic light
      scattering to optimize solutions for crystallization trials.
AB  - Detergents are widely used for the isolation and solubilization of membrane
      proteins to support crystallization and structure determination. Detergents are
      amphiphilic molecules that form micelles once the characteristic critical micelle
      concentration (CMC) is achieved and can solubilize membrane proteins by the
      formation of micelles around them. The results are presented of a study of
      micelle formation observed by in situ dynamic light-scattering (DLS) analyses
      performed on selected detergent solutions using a newly designed advanced
      hardware device. DLS was initially applied in situ to detergent samples with a
      total volume of approximately 2 ul. When measured with DLS, pure detergents show
      a monodisperse radial distribution in water at concentrations exceeding the CMC.
      A series of all-trans n-alkyl-beta-D-maltopyranosides, from n-hexyl to n
      tetradecyl, were used in the investigations. The results obtained verify that the
      application of DLS in situ is capable of distinguishing differences in the
      hydrodynamic radii of micelles formed by detergents differing in length by only a
      single CH2 group in their aliphatic tails. Subsequently, DLS was applied to
      investigate the distribution of hydrodynamic radii of membrane proteins and
      selected water-insoluble proteins in presence of detergent micelles. The results
      confirm that stable protein-detergent complexes were prepared for (i)
      bacteriorhodopsin and (ii) FetA in complex with a ligand as examples of
      transmembrane proteins. A fusion of maltose-binding protein and the Duck
      hepatitis B virus X protein was added to this investigation as an example of a
      non-membrane-associated protein with low water solubility. The increased
      solubility of this protein in the presence of detergent could be monitored, as
      well as the progress of proteolytic cleavage to separate the fusion partners.
      This study demonstrates the potential of in situ DLS to optimize solutions of
      protein-detergent complexes for crystallization applications. 

PMID- 25615975
TI  - Crystallization and preliminary X-ray crystallographic analysis of the CARD
      domain of apoptosis repressor with CARD (ARC).
AB  - Apoptosis repressor with caspase-recruiting domain (ARC) is an apoptosis
      repressor that inhibits both intrinsic and extrinsic apoptosis signalling. Human
      ARC contains an N-terminal caspase-recruiting domain (CARD domain) and a C
      terminal proline- and glutamic acid-rich (P/E-rich) domain. The CARD domain in
      ARC is the domain that is directly involved in inhibition of the extrinsic
      pathway. In this study, the N-terminal CARD domain of ARC was overexpressed,
      purified and crystallized. X-ray diffraction data were collected to a resolution
      of 2.1 A and the crystals were found to belong to space group P6(1) or P65, with
      unit-cell parameters a=98.28, b=98.28, c=51.86 A, alpha=90, beta=90, gamma=120
      degrees .

PMID- 25615976
TI  - Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L
      glutamate synthase/kinase with and without a His tag bound to N-acetyl-L
      glutamate.
AB  - Structures of the catalytic N-acetyltransferase (NAT) domain of the bifunctional
      N-acetyl-L-glutamate synthase/kinase (NAGS/K) from Xylella fastidiosa bound to N
      acetyl-L-glutamate (NAG) with and without an N-terminal His tag have been solved
      and refined at 1.7 and 1.4 A resolution, respectively. The NAT domain with an N
      terminal His tag crystallized in space group P4(1)2(1)2, with unit-cell
      parameters a=b=51.72, c=242.31 A. Two subunits form a molecular dimer in the
      asymmetric unit, which contains ~41% solvent. The NAT domain without an N
      terminal His tag crystallized in space group P21, with unit-cell parameters
      a=63.48, b=122.34, c=75.88 A, beta=107.6 degrees . Eight subunits, which form
      four molecular dimers, were identified in the asymmetric unit, which contains
      ~38% solvent. The structures with and without the N-terminal His tag provide an
      opportunity to evaluate how the His tag affects structure and function.
      Furthermore, multiple subunits in different packing environments allow an
      assessment of the plasticity of the NAG binding site, which might be relevant to
      substrate binding and product release. The dimeric structure of the X. fastidiosa
      N-acetytransferase (xfNAT) domain is very similar to that of human N
      acetyltransferase (hNAT), reinforcing the notion that mammalian NAGS is
      evolutionally derived from bifunctional bacterial NAGS/K.

PMID- 25615977
TI  - Crystallization and preliminary X-ray analysis of the NAD+-reducing [NiFe]
      hydrogenase from Hydrogenophilus thermoluteolus TH-1.
AB  - NAD+-reducing [NiFe] hydrogenases catalyze the oxidoreduction of dihydrogen
      concomitant with the interconversion of NAD+ and NADH. Here, the isolation,
      purification and crystallization of the NAD+-reducing [NiFe] hydrogenase from
      Hydrogenophilus thermoluteolus TH-1 are reported. Crystals of the NAD+-reducing
      [NiFe] hydrogenase were obtained within one week from a solution containing
      polyethylene glycol using the sitting-drop vapour-diffusion method and micro
      seeding. The crystal diffracted to 2.58 A resolution and belonged to space group
      C2, with unit-cell parameters a=131.43, b=189.71, c=124.59 A, beta=109.42 degrees
      . Assuming the presence of two NAD+-reducing [NiFe] hydrogenase molecules in the
      asymmetric unit, VM was calculated to be 2.2 A3 Da(-1), which corresponds to a
      solvent content of 43%. Initial phases were determined by the single-wavelength
      anomalous dispersion method using the anomalous signal from the Fe atoms.

PMID- 25615978
TI  - Cleaning protocols for crystallization robots: preventing protease contamination.
AB  - The protease in the commonly used commercial low-foam enzyme cleaner Zymit cannot
      be completely blocked by EDTA, a widely used inhibitor of metalloproteases, at
      concentrations of up to 5 mM. Severe protein degradation was observed in
      crystallization drops after EDTA-containing wash steps unless residual Zymit
      protease was removed with NaOH at a concentration of at least 0.1 M. Wash steps
      with 0.1% SDS were also ineffective in completely removing the remaining Zymit
      activity. Protocols including wash steps with at least 0.1 M NaOH, as for example
      specified in the original ZENM protocol, are recommended to completely deactivate
      Zymit protease activity. 

PMID- 25615979
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of SpaD,
      a backbone-pilin subunit encoded by the fimbrial spaFED operon in Lactobacillus
      rhamnosus GG.
AB  - SpaD is the predicted backbone-pilin subunit of the SpaFED pilus, whose loci are
      encoded by the fimbrial spaFED operon in Lactobacillus rhamnosus GG, a Gram
      positive gut-adapted commensal strain with perceived probiotic benefits. In this
      study, soluble recombinant SpaD protein was overproduced in Escherichia coli and
      then purified by Ni2+-chelating affinity and gel-filtration chromatography. After
      limited proteolysis with alpha-chymotrypsin, good-quality crystals of SpaD were
      obtained which diffracted beyond 2.0 A resolution. These crystals belonged to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a=50.11,
      b=83.27, c=149.65 A. For phasing, sodium iodide-derivatized crystals were
      prepared using the halide quick-soaking method and diffraction data were
      collected in-house to a resolution of 2.2 A. An interpretable electron-density
      map was successfully obtained using single-wavelength anomalous diffraction
      (SAD).

PMID- 25615980
TI  - Purification, crystallization and preliminary X-ray crystallographic studies of
      Rv3899c from Mycobacterium tuberculosis.
AB  - Rv3899c, a hypothetical protein from Mycobacterium tuberculosis that is conserved
      within the mycobacteria, is predicted to be secreted and has been found in
      culture filtrates. Here, Rv3899c has been cloned, expressed in Escherichia coli
      and purified using standard chromatographic techniques. The hanging-drop vapour
      diffusion method with PEG 3350 as a precipitant was used to crystallize the
      protein. N-terminal sequencing results showed that the amino-acid sequence of the
      crystallized protein began with GATAG, indicating that it is a fragment
      containing residues 184-410 of Rv3899c. Rv3899c184-410 crystals exhibited the
      symmetry of space group P2(1)2(1)2(1), with unit-cell parameters a=49.88,
      b=54.72, c=75.52 A, alpha=beta=gamma=90 degrees , and diffracted to a resolution
      of 1.90 A.

PMID- 25615981
TI  - Cloning, expression, refolding, purification and preliminary crystallographic
      analysis of the sensory domain of the Campylobacter chemoreceptor for aspartate A
      (CcaA).
AB  - In Campylobacter jejuni, chemotaxis and motility have been identified as
      important virulence factors that are required for host colonization and invasion.
      Chemotactic recognition of extracellular signals is mediated by the periplasmic
      sensory domains of its transducer-like proteins (Tlps). In this study, the
      sensory domain of the C. jejuni chemoreceptor for aspartate A (CcaA) has been
      expressed in Escherichia coli and purified from inclusion bodies. The urea
      denatured protein was refolded and then crystallized by the hanging-drop vapour
      diffusion method using PEG 3350 as a precipitating agent. A complete data set has
      been collected to 1.4 A resolution using cryocooling conditions and synchrotron
      radiation. The crystals belonged to space group P1, with unit-cell parameters
      a=39.3, b=43.3, c=50.9 A, alpha=92.5, beta=111.4, gamma=114.7 degrees .

PMID- 25615983
TI  - Crystal face identification by Raman microscopy for assessment of crystal habit
      of a drug.
AB  - Crystal habit is one of the key crystallographic characteristics of active
      pharmaceutical ingredients (APIs), especially those that are poorly soluble. X
      ray powder diffraction has commonly been used to assess crystal habit; however,
      it can only provide macro-information regarding crystal habit for a whole powder
      sample, not for individual crystals. We describe an approach that uses Raman
      microscopy for the identification of crystal faces to assess crystal habit at the
      individual particle level. An antiepileptic agent, phenytoin, was used as the
      model substance. Phenytoin crystals form a primitive orthorhombic cell. Raman
      microscopy was used to identify three different patterns of Raman spectra,
      corresponding to the crystallographic axis that was parallel to the polarization
      direction of the excitation laser. Thus, a combination of Raman spectra, in which
      the polarization direction was horizontal and vertical to the morphologically
      long axis of the crystal, characterized the crystal face. Phenytoin crystals were
      prepared under various conditions, and the horizontal/vertical combinations of
      Raman spectra were recorded for individual crystals. The dominantly exposed
      crystal faces for each condition were identified. This analytical method enables
      micro-view assessments of crystal habit, which are helpful for identifying the
      habits of APIs alone and in formulations. 

PMID- 25615982
TI  - The three-dimensional structure of the cellobiohydrolase Cel7A from Aspergillus
      fumigatus at 1.5 A resolution.
AB  - The enzymatic degradation of plant cell-wall cellulose is central to many
      industrial processes, including second-generation biofuel production. Key players
      in this deconstruction are the fungal cellobiohydrolases (CBHs), notably those
      from family GH7 of the carbohydrate-active enzymes (CAZY) database, which are
      generally known as CBHI enzymes. Here, three-dimensional structures are reported
      of the Aspergillus fumigatus CBHI Cel7A solved in uncomplexed and disaccharide
      bound forms at resolutions of 1.8 and 1.5 A, respectively. The product complex
      with a disaccharide in the +1 and +2 subsites adds to the growing three
      dimensional insight into this family of industrially relevant biocatalysts. 

PMID- 25615984
TI  - Tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier for targeted
      intracellular delivery of paclitaxel.
AB  - In the present study, we constructed a tumor-targeting and pH-sensitive
      lipoprotein-mimic nanocarrier containing paclitaxel (FA-BSA-LC/DOPE-PTX), by
      adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and oleic acid as pH
      sensitive components into the formulation of lipid core and then coating with
      folic acid modified bovine serum albumin (FA-BSA) for tumor targeting activity.
      In vitro drug release study demonstrated that paclitaxel (PTX) was released from
      FA-BSA-LC/DOPE in a pH-dependent manner. The vitro cytotoxicity assays showed
      that all the blank nanocarriers were nontoxic. However, MTT assay showed that FA
      BSA-LC/DOPE-PTX was highly cytotoxic. Cellular uptake experiments analyzed with
      flow cytometry and laser scan confocal microscope (LSCM) revealed that FA-BSA
      LC/DOPE was taken up in great amount via folate receptor-mediated endocytosis and
      pH-sensitive release of drug to cytoplasm. Furthermore, the study of
      intracellular drug release behavior demonstrated that the FA-BSA-LC/DOPE escaped
      from lysosomes and released drug into cytoplasm. The in vivo targeting activity
      showed that the nanocarrier selectively targeted tumor and had long residence
      time for BSA layer increased the stability in blood. Moreover, FA-BSA-LC/DOPE-PTX
      produced very marked anti-tumor activity in tumor-bearing mice in vivo.
      Therefore, FA-BSA-LC/DOPE as biocompatible, tumor-targeting and pH-sensitive
      lipoprotein-mimic nanocarrier is a promising system for effective intracellular
      delivery of PTX to tumor. 

PMID- 25615985
TI  - Preparation and evaluation of submicron-carriers for naringenin topical
      application.
AB  - Submicron emulsion system is one kind of submicron-carrier that can ensure close
      contact and increase the amount of drug transport into the skin. In the present
      study, naringenin was loaded into a submicron emulsion system for topical
      applications. The enhancement effect of drug permeability through skin,
      stability, and skin irritation of naringenin-loaded submicron emulsions were
      evaluated. The results showed that the transdermal amount and deposition amount
      in skin of naringenin from submicron emulsion formulations were significantly
      increased when compared to the control group of saturated aqueous solution of
      naringenin. The drug-loaded submicron emulsions showed thermodynamic stability
      after centrifugation and cooling-heating cycle tests. The level of drug was more
      than 98% after 3 months of storage at 25 degrees C and 40 degrees C. In skin
      irritation test, the result also demonstrated that naringenin-loaded submicron
      emulsion had less skin irritation, indicating that the formulation can possibly
      be developed for topical application.

PMID- 25615986
TI  - Solubilization of menthol by platycodin D in aqueous solution: an integrated
      study of classical experiments and dissipative particle dynamics simulation.
AB  - Menthol (M) and platycodin D (PD) are the main active ingredients in Mentha
      haplocalyx and Platycodon grandiflorum A. DC., respectively. They are commonly
      used in combination in traditional Chinese medicine. In this study, laboratory
      experiments and computer simulations were used to investigate the solubilization
      of M by PD, which was believed to be one of the main causes of the synergistic
      effect of M. haplocalyx and P. grandiflorum A. DC. Results showed that both the
      method by which M was added and the concentration of PD had significant effects
      on the solubilization efficiency of M, and these influences were closely
      associated with each other. Temperature, an important environmental condition,
      was also found to have a significant effect on the solubilization effect of PD.
      These findings not only clarify the molecular basis of the solubilization effect,
      including amount solubilized at the macroscale and the structures of the
      micelles, and the drug loading mechanisms and processing at the mesoscale. This
      work may provide some guidance for the further development of saponins and
      fundamental research in the drug delivery system. 

PMID- 25615987
TI  - Liposome incorporated ion sensitive in situ gels for opthalmic delivery of
      timolol maleate.
AB  - This study was aimed to design a liposomal based ion-sensitive in situ ophthalmic
      delivery system of timolol maleate (TM). The TM liposome was produced by the
      reverse evaporation technique coupled with pH-gradients method (REVPR), and then
      was incorporated into deacetylated gellan gum gels. The TM liposome was
      demonstrated to be a round and uniform shape in TEM pictures. Compared with the
      TM eye drops, the TM liposome produced a 1.93 folds increase in apparent
      permeability coefficients (Papp), resulting in a significant increase of the
      corneal penetration. The TM-loaded liposome incorporated ion sensitive in situ
      gels (TM L-ISG) showed longer retention time on corneal surface compared with the
      eye drops using gamma scintigraphy technology. Draize testing showed that TM L
      ISG was non-irritant for ocular tissues. The biggest efficacy of TM L-ISG
      occurred 30 min after eye drops administration, and efficacy disappeared after
      240min. Then, compared with the eye drops, the optimal TM L-ISG could quickly
      reduce the intraocular pressure and the effective time was significantly longer
      (P<=0.05). These results indicate that liposome incorporated ion sensitive in
      situ gels have a potential ability for the opthalmic delivery.

PMID- 25615989
TI  - Health and wellbeing: giving weight to the argument.

PMID- 25615988
TI  - Sleep restriction during simulated wildfire suppression: effect on physical task
      performance.
AB  - OBJECTIVES: To examine the effects of sleep restriction on firefighters' physical
      task performance during simulated wildfire suppression. METHODS: Thirty-five
      firefighters were matched and randomly allocated to either a control condition (8
      hour sleep opportunity, n = 18) or a sleep restricted condition (4-hour sleep
      opportunity, n = 17). Performance on physical work tasks was evaluated across
      three days. In addition, heart rate, core temperature, and worker activity were
      measured continuously. Rate of perceived and exertion and effort sensation were
      evaluated during the physical work periods. RESULTS: There were no differences
      between the sleep-restricted and control groups in firefighters' task
      performance, heart rate, core temperature, or perceptual responses during self
      paced simulated firefighting work tasks. However, the sleep-restricted group were
      less active during periods of non-physical work compared to the control group.
      CONCLUSIONS: Under self-paced work conditions, 4 h of sleep restriction did not
      adversely affect firefighters' performance on physical work tasks. However, the
      sleep-restricted group were less physically active throughout the simulation.
      This may indicate that sleep-restricted participants adapted their behaviour to
      conserve effort during rest periods, to subsequently ensure they were able to
      maintain performance during the firefighter work tasks. This work contributes new
      knowledge to inform fire agencies of firefighters' operational capabilities when
      their sleep is restricted during multi-day wildfire events. The work also
      highlights the need for further research to explore how sleep restriction affects
      physical performance during tasks of varying duration, intensity, and complexity.

PMID- 25615990
TI  - Soaps and serenity: care the Cantonese way.

PMID- 25615991
TI  - Clean intermittent self-catheterisation: working with patients.
AB  - Clean intermittent self-catheterisation is carried out when the bladder cannot be
      emptied adequately by voiding. Because learning how to self-catheterise can be
      daunting, it is essential that the nurse has the time, knowledge and skills
      necessary support the patient during the learning phase, so that he or she can
      develop confidence and master the technique. Causes for urinary retention are
      considered and step-by-step instructions are given for both female and male
      patients, including problems that may be encountered and how these can be
      overcome. Examples of catheters and other aids available are suggested, with
      reference to particular features they may have, to overcome difficulties or to
      assist patients with particular needs. Issues including infection, frequency of
      catheterisation and fluid intake are also discussed. 

PMID- 25615992
TI  - Quiz game teaching format versus didactic lectures.
AB  - BACKGROUND: Lecturing has been traditionally used as the core teaching strategy
      in university education in all disciplines. However, new research in education
      suggests that other formats such as game teaching could be more effective. AIM:
      To compare students' performance, satisfaction and retention of knowledge between
      a Jeopardy!-style game format and a didactic lecture format in teaching the
      subject of models for organising patient care to fourth-year nursing students.
      METHODS: A parallel-group randomised controlled trial was conducted. Participants
      were fourth-year nursing students who registered in the second semester of 2012
      2013 and enrolled in the Nursing Management and Ethics in Nursing Course in the
      Community Health Department. RESULTS: 66 students completed the study (34 in the
      quiz game group and 32 in the lecture group). Pre-test results showed no
      significant difference between the two groups in their achievement scores.
      However, in the immediate achievement post-test and the retention test the
      students in the quiz group scored significantly better than those in the lecture
      group. A satisfaction questionnaire showed that the game format was well liked
      and accepted by students as a more satisfying teaching method. CONCLUSION: This
      study is the first of its kind in Jordan to explore the effectiveness of this
      particular game format versus the lecture format. RESULTS suggest that the game
      format was well liked and accepted by students as a more satisfying teaching
      method. Additionally, it appeared to be a better method of education as it
      promoted greater information retention.

PMID- 25615993
TI  - Nursing care to facilitate and support 'good' grieving.
AB  - In this monthly column, Aysha Mendes discusses the importance of the role nurses
      play in the grieving process, and discusses what constitutes good support for
      patients who are dying and their relatives. 

PMID- 25615994
TI  - Successful treatment of infantile haemangioma with propranolol.

PMID- 25615995
TI  - A portable, disposable system for negative-pressure wound therapy.
AB  - Negative-pressure wound therapy (NPWT) imparts a number of clinical effects that
      promote a healing response and, as such, is a well-established means of treating
      a variety of wound types. Historically, the technique has been primarily used in
      the hospital setting; however, the introduction of more portable devices has led
      to an increase in the use of NPWT in the homecare setting, thereby facilitating
      early discharge of patients from hospital and continuity of care in the
      community. Portable NPWT devices also have the potential to impact positively on
      patients' quality of life, allowing increased mobility and freedom to undertake
      normal activities of daily living. Following the development of its standard
      Avance(r) NPWT system and associated dressing kits, Molnlycke Health Care
      (Gothenburg, Sweden) has introduced a single-patient-use, disposable NPWT system;
      Avance Solo. This has been developed with a view to maximising patient freedom
      and mobility, providing a single-patient-use NPWT solution for multi-week
      treatment to allow quick and easy discharge of patients from hospital to home,
      and reducing some of the challenges of logistics and administration associated
      with the provision of NPWT for the caregiver. As with the standard NPWT system,
      the single-patient use system is supplied with a number of products incorporating
      Safetac(r) adhesive technology to minimise the risk of patients suffering
      unnecessary pain and trauma associated with dressing changes. This article
      presents a series of case studies describing procedures and outcomes following
      the application of the Avance Solo single-patient-use system. 

PMID- 25615996
TI  - Paediatric nurses' attitudes towards the promotion of healthy eating.
AB  - This study assessed paediatric nurses' attitudes towards promoting healthy eating
      and their opinions regarding nurses as role models for health. In all, 67 nurses
      from 14 wards at an acute hospital trust completed questionnaires on weight,
      diet, physical activity, self-efficacy and attitudes towards nurses as role
      models for health. Forty-eight percent felt that they could incorporate health
      promotion into their patient care better, and 84% believed that nurses should
      present themselves as role models for health. Nurses felt that their own health
      behaviours influenced the quality of their care: 77% reported that patients and
      families would heed advice better from those who appeared to follow it
      themselves, and 48% reported difficulties in promoting health behaviours they did
      not adhere to themselves. These views were inconsistent with their own lifestyle
      choices, since one third of respondents did not meet physical-activity
      guidelines, almost half were an unhealthy weight, and the majority did not
      consume five portions of fruits/vegetables per day. Paediatric nurses identified
      barriers and facilitators to promoting healthy eating. Education, training and
      access to evidence-based resources may help to increase paediatric nurses'
      confidence to promote healthy eating to children and their families. Hospital
      workplaces should make provision to support nurses who seek to improve their own
      health. 

PMID- 25615997
TI  - Will MyNHS increase public confidence in care delivery?
AB  - Professor Alan Glasper from the University of Southampton discusses the potential
      impact of MyNHS, designed to give members of the public in England access to data
      to allow them to compare the performance of their local NHS hospital. 

PMID- 25615998
TI  - The Care Quality Commission gets tough over NHS complaints.
AB  - John Tingle discusses a new publication on complaints in health and social care
      by the Care Quality Commission (CQC). 

PMID- 25615999
TI  - Written communication: from staff nurse to nurse consultant.

PMID- 25616000
TI  - Generalist or specialist in nurse education?

PMID- 25616001
TI  - Bring back the E-grade nurse.

PMID- 25616002
TI  - Long-term intermittent feeding restores impaired GR signaling in the hippocampus
      of aged rat.
AB  - Diminished glucocorticoid signaling is associated with an age-related decline in
      hippocampal functioning. In this study we demonstrate the effect of intermittent,
      every other day (EOD) feeding on the glucocorticoid hormone/glucocorticoid
      receptor (GR) system in the hippocampus of middle-aged (18-month-old) and aged
      (24-month-old) Wistar rats. In aged ad libitum-fed rats, a decrease in the level
      of total GR and GR phosphorylated at Ser(232) (pGR) was detected. Conversely,
      aged rats subjected to EOD feeding, starting from 6 months of age, showed an
      increase in GR and pGR levels and a higher content of hippocampal corticosterone.
      Furthermore, prominent nuclear staining of pGR was observed in CA1 pyramidal and
      DG granule neurons of aged EOD-fed rats. These changes were accompanied by
      increased Sgk-1 and decreased GFAP transcription, pointing to upregulated
      transcriptional activity of GR. EOD feeding also induced an increase in the
      expression of the mineralocorticoid receptor. Our results reveal that
      intermittent feeding restores impaired GR signaling in the hippocampus of aged
      animals by inducing rather than by stabilizing GR signaling during aging. 

PMID- 25616003
TI  - NO-dependent proliferation and migration induced by Vitamin D in HUVEC.
AB  - Recently, Vitamin D (Vit. D) has gained importance in cellular functions of a
      wide range of extraskeletal organs and target tissues, other than bone. In
      particular, Vit. D has displayed important beneficial effects in the
      cardiovascular system. Although little is known about the mechanism by which this
      response is exerted, a Vit. D-induced eNOS-dependent nitric oxide (NO) production
      in endothelial cells (EC) has been reported. The aim of this study was to
      evaluate whether Vit. D administration could affect human EC proliferation and/or
      migration through NO production. For this purpose, HUVEC (human umbilical vein
      endothelial cells) were used to evaluate Vit. D effects on cell proliferation and
      migration in a 3D matrix. Experiments were also performed in the presence of the
      specific VDR ligand ZK159222 and eNOS inhibitor L-NAME. This study demonstrated
      that Vit. D can promote both HUVEC proliferation and migration in a 3D matrix.
      These effects were NO dependent, since HUVEC proliferation and migration were
      abrogated along with Vit. D induced MMP-2 expression by inhibiting eNOS activity
      by L-NAME. These findings support the role of Vit. D in the angiogenic process,
      suggesting new applications for Vit. D in tissue repair and wound healing. 

PMID- 25616004
TI  - Oscillatory brain activity in the alpha range is modulated by the content of word
      prompted mental imagery.
AB  - Mental imagery is a fundamental cognitive process of interest to basic scientists
      and clinical researchers. This study examined large-scale oscillatory brain
      activity in the alpha band (8-12 Hz) during language-driven mental imagery using
      dense-array EEG. Three experiments demonstrated relative increases in alpha
      amplitude: (1) during imagery prompted by words compared to fixation without
      imagery instruction, (2) during imagery of word content compared to imagery of
      geometric shapes, and (3) during imagery of emotionally evocative words compared
      to imagery of less emotionally arousing content. Alpha increases for semantically
      loaded imagery were observed in parieto-occipital regions, sustained throughout
      the imagery period. Findings imply that alpha oscillations index active memory
      and internal cognitive processing, reflecting neural communication in cortical
      networks representing motor, semantic, and perceptual aspects of the imagined
      scene. 

PMID- 25616005
TI  - Mechanism of inactivation of gamma-aminobutyric acid aminotransferase by (1S,3S)
      3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115).
AB  - gamma-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate
      (PLP)-dependent enzyme that degrades GABA, the principal inhibitory
      neurotransmitter in mammalian cells. When the concentration of GABA falls below a
      threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels
      in the brain, which can terminate seizures as well as have potential therapeutic
      applications in treating other neurological disorders, including drug addiction.
      Among the analogues that we previously developed, (1S,3S)-3-amino-4
      difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater
      potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug
      (Sabril) for the treatment of infantile spasms and refractory adult epilepsy.
      Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical
      trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism
      based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the
      difluoromethylene group to a carboxylic acid with concomitant loss of two
      fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The
      partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone
      2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21).
      Time-dependent inactivation occurs by a conformational change induced by the
      formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP
      (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to
      form an electrostatic interaction between Arg445 and the newly formed carboxylate
      produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a
      noncovalent, tightly bound complex. This represents a novel mechanism for
      inactivation of GABA-AT and a new approach for the design of mechanism-based
      inactivators in general. 

PMID- 25616006
TI  - Assessing readiness for transition from paediatric to adult health care: Revision
      and psychometric evaluation of the Am I ON TRAC for Adult Care questionnaire.
AB  - AIM: To refine and psychometrically test the Am I ON TRAC for Adult Care
      questionnaire. BACKGROUND: Inadequate transition to adult care for adolescents
      with special healthcare needs has been associated with greater risk of treatment
      non-adherence, lack of medical follow-up, increased morbidity and mortality.
      Presently, there are no well-validated measures assessing adolescents' readiness
      to transition from paediatric to adult medical care. DESIGN: Descriptive cross
      sectional study. METHODS: The Am I ON TRAC for Adult Care questionnaire was
      refined to improve the instrument's methodological soundness. A literature review
      informed the revisions. A convenience sample of 200 adolescents, 12-19 years, was
      recruited from four outpatient clinics at a paediatric hospital in Western Canada
      between April-June 2012. Construct validity was evaluated by Exploratory Factory
      Analysis; concurrent validity was assessed using the Psychosocial Maturity Index.
      Internal consistency was evaluated by computing Cronbach's alpha estimates.
      RESULTS: Factor analysis of the knowledge items identified a 14-item
      unidimensional scale. Knowledge and behaviour sub-scale scores increased with
      age, with a stronger relationship between knowledge and age. Psychosocial
      maturity correlated with both sub-scale scores, but had a stronger association
      with behaviour. Psychosocial maturity and age had a weak but significant
      correlation suggesting age is a loose proxy for maturity. Only 27% of 17-year
      olds, but 62% 18-year olds, scored above the behaviour cut-off for transition
      readiness. CONCLUSION: The revised Am I ON TRAC for Adult Care questionnaire is a
      psychometrically sound measure that has potential to be used as a readiness
      assessment tool in both clinical practice and research.

PMID- 25616007
TI  - Prediction of methylmercury accumulation in rice grains by chemical extraction
      methods.
AB  - To explore the possibility of using chemical extraction methods to predict
      phytoavailability/bioaccumulation of soil-bound MeHg, MeHg extractions by three
      widely-used extractants (CaCl2, DTPA, and (NH4)2S2O3) were compared with MeHg
      accumulation in rice grains. Despite of variations in characteristics of
      different soils, MeHg extracted by (NH4)2S2O3 (highly affinitive to MeHg)
      correlated well with grain MeHg levels. Thus (NH4)2S2O3 extraction, solubilizing
      not only weakly-bound and but also strongly-bound MeHg, may provide a measure of
      'phytoavailable MeHg pool' for rice plants. Besides, a better prediction of grain
      MeHg levels was obtained when growing condition of rice plants was also
      considered. However, MeHg extracted by CaCl2 or DTPA, possibly quantifying
      'exchangeable MeHg pool' or 'weakly-complexed MeHg pool' in soils, may not
      indicate phytoavailable MeHg or predict grain MeHg levels. Our results provided
      the possibility of predicting MeHg phytoavailability/bioaccumulation by
      (NH4)2S2O3 extraction, which could be useful in screening soils for rice
      cultivation in contaminated areas. 

PMID- 25616009
TI  - Large Margin Local Estimate With Applications to Medical Image Classification.
AB  - Medical images usually exhibit large intra-class variation and inter-class
      ambiguity in the feature space, which could affect classification accuracy. To
      tackle this issue, we propose a new Large Margin Local Estimate (LMLE)
      classification model with sub-categorization based sparse representation. We
      first sub-categorize the reference sets of different classes into multiple
      clusters, to reduce feature variation within each subcategory compared to the
      entire reference set. Local estimates are generated for the test image using
      sparse representation with reference subcategories as the dictionaries. The
      similarity between the test image and each class is then computed by fusing the
      distances with the local estimates in a learning-based large margin aggregation
      construct to alleviate the problem of inter-class ambiguity. The derived
      similarities are finally used to determine the class label. We demonstrate that
      our LMLE model is generally applicable to different imaging modalities, and
      applied it to three tasks: interstitial lung disease (ILD) classification on high
      resolution computed tomography (HRCT) images, phenotype binary classification and
      continuous regression on brain magnetic resonance (MR) imaging. Our experimental
      results show statistically significant performance improvements over existing
      popular classifiers. 

PMID- 25616008
TI  - A Model of Population and Subject (MOPS) Intensities With Application to Multiple
      Sclerosis Lesion Segmentation.
AB  - White matter (WM) lesions are thought to play an important role in multiple
      sclerosis (MS) disease burden. Recent work in the automated segmentation of white
      matter lesions from magnetic resonance imaging has utilized a model in which
      lesions are outliers in the distribution of tissue signal intensities across the
      entire brain of each patient. However, the sensitivity and specificity of lesion
      detection and segmentation with these approaches have been inadequate. In our
      analysis, we determined this is due to the substantial overlap between the whole
      brain signal intensity distribution of lesions and normal tissue. Inspired by the
      ability of experts to detect lesions based on their local signal intensity
      characteristics, we propose a new algorithm that achieves lesion and brain tissue
      segmentation through simultaneous estimation of a spatially global within-the
      subject intensity distribution and a spatially local intensity distribution
      derived from a healthy reference population. We demonstrate that MS lesions can
      be segmented as outliers from this intensity model of population and subject. We
      carried out extensive experiments with both synthetic and clinical data, and
      compared the performance of our new algorithm to those of state-of-the art
      techniques. We found this new approach leads to a substantial improvement in the
      sensitivity and specificity of lesion detection and segmentation. 

PMID- 25616010
TI  - Multi-TI Arterial Spin Labeling MRI with Variable TR and Bolus Duration for
      Cerebral Blood Flow and Arterial Transit Time Mapping.
AB  - Arterial spin labeling (ASL) is an MRI perfusion imaging method from which
      quantitative cerebral blood flow (CBF) can be calculated. We present a multi-TI
      ASL method (multi-TI integrated ASL) in which variable post-labeling delays and
      variable TRs are used to improve the estimation of arterial transit time (ATT)
      and CBF while shortening the scan time by 41% compared to the conventional
      methods. Variable bolus widths allow for T1 and M0 estimation from raw ASL data.
      Multi-TI integrated pseudo-continuous ASL images were collected at 7 TI times
      ranging 100-4300 ms. Voxel-wise T1 and M0 maps were estimated, then CBF and ATT
      maps were created using the estimated T1 tissue map. All maps were consistent
      with physiological values reported in the literature. Based on simulations and in
      vivo comparisons, this method demonstrates higher CBF and ATT estimation
      efficiency than other ATT acquisition methods and better fit to the perfusion
      model. It produces CBF maps with reduced sensitivity to errors from ATT and
      tissue T1 variations. The estimated M0, T1, and ATT maps also have potential
      clinical utility. The method requires a single scan acquired within a clinically
      acceptable scan time (under 6 minutes) and with low sensitivity to motion.

PMID- 25616011
TI  - Evidence for a small hole pocket in the Fermi surface of underdoped YBa2Cu3Oy.
AB  - In underdoped cuprate superconductors, the Fermi surface undergoes a
      reconstruction that produces a small electron pocket, but whether there is
      another, as yet, undetected portion to the Fermi surface is unknown. Establishing
      the complete topology of the Fermi surface is key to identifying the mechanism
      responsible for its reconstruction. Here we report evidence for a second Fermi
      pocket in underdoped YBa2Cu3Oy, detected as a small quantum oscillation frequency
      in the thermoelectric response and in the c-axis resistance. The field-angle
      dependence of the frequency shows that it is a distinct Fermi surface, and the
      normal-state thermopower requires it to be a hole pocket. A Fermi surface
      consisting of one electron pocket and two hole pockets with the measured areas
      and masses is consistent with a Fermi-surface reconstruction by the charge
      density-wave order observed in YBa2Cu3Oy, provided other parts of the
      reconstructed Fermi surface are removed by a separate mechanism, possibly the
      pseudogap. 

PMID- 25616013
TI  - Phylogenetics and molecular clocks reveal the repeated evolution of ant-plants
      after the late Miocene in Africa and the early Miocene in Australasia and the
      Neotropics.
AB  - Ant-plant symbioses involve over 110 ant species in five subfamilies that are
      facultative or obligate occupants of stem, leaf or root domatia formed by
      hundreds of ant-plant species. The phylogenetic distribution and geological ages
      of these associations, and the frequency of gains or losses of domatium, are
      largely unknown. We compiled an up-to-date list of ant domatium-bearing plants,
      estimated their probable true number from model-based statistical inference,
      generated dated phylogenies that include c. 50% of ant-plant lineages, and traced
      the occurrence of domatia and extrafloral nectaries on a 1181-species tree, using
      likelihood and Bayesian methods. We found 681 vascular plants with domatia (159
      genera in 50 families) resulting from minimally 158 inferred domatium origins and
      43 secondary losses over the last 19 Myr. The oldest African ant-plant symbioses
      are younger than those in Australasia and the Neotropics. The best statistical
      model suggests that the true number of myrmecophytes may approach 1140 species.
      The phylogenetic distribution of ant-plants shows that domatia evolved from a
      range of pre-adapted morphological structures and have been lost frequently,
      suggesting that domatia have no generalizable effect on diversification. The
      Miocene origin of ant-plant symbioses is consistent with inferred changes in diet
      and behaviour during ant evolution. 

PMID- 25616014
TI  - Long-term outcome in selective dorsal rhizotomy in spastic cerebral palsy:
      differentiation in mobility levels is needed.

PMID- 25616015
TI  - Semi-analytical description of the S=9/2 quadrupole nutation NMR experiment:
      multinuclear application to (113) In and (115) In in indium phosphide.
AB  - The density matrix of a spin S=9/2 excited by a radiofrequency pulse is
      calculated. The interaction involved during the excitation of the spin system is
      first-order quadrupolar. Consequently, the results are valid for any ratio of the
      quadrupolar coupling omegaQ to the pulse amplitude omega1 . The behavior of the
      central transition intensities versus the pulse length is discussed. The (115) In
      and (113) In nuclei in a powdered sample of indium phosphide (InP) are used to
      illustrate the results. It is found that the ratio of the quadrupolar coupling
      constants determined in this work is in excellent agreement with the ratio of the
      quadrupole moments of the two nuclei.

PMID- 25616016
TI  - Effect of capping ligands and TiO2 supporting on the optical properties of a
      (CdSe)13 cluster.
AB  - The influence of different aliphatic and aromatic ligand molecules on the
      electronic properties of CdSe quantum dots (QDs) has been examined by employing
      density functional theory (DFT). Optical spectra were simulated with the real
      time time-dependent DFT (RT-TDDFT) methodology. The assignment of the first
      absorption peak features that occur in these spectra was done by taking into
      account the composition of the frontier molecular orbitals (MOs) of the different
      systems. While the aliphatic ligands considered-amine, thiol, and phospine oxides
      did not show any major influence on the electronic absorption spectra, some of
      the aromatic ligands do have a noticeable impact on the optoelectronic properties
      of the QD. Aromatic ligands are mainly aniline-type molecules; additionally, a
      thiophenol and uracil were employed to saturate the dangling bonds on the Cd
      atoms. Finally, a more realistic model of a QD-sensitized solar cell consisting
      of methylamine-capped (CdSe)13 cluster linked to a TiO2 nanoparticle through a
      mercaptopropionate bridge was considered. The simulations again show that the
      lowest electronic excitation takes place within the QD subunit, demonstrating the
      indirect nature of the electron injection mechanism operating in these solar
      cells. 

PMID- 25616017
TI  - Successful anti-viral treatment improves survival of patients with advanced liver
      disease due to chronic hepatitis C.
AB  - BACKGROUND: Long-term outcome of chronic hepatitis C patients with successful
      viral eradication seems to be promising. AIM: To evaluate mortality, incidence of
      hepatocellular carcinoma (HCC), liver failure and liver transplantation in
      sustained virological responders (SVR) and non-SVR patients with different stages
      of fibrosis. METHODS: Seven hundred and fourteen patients with a follow-up of 7.2
      (1-21.1) years (age: 51.4 +/- 12.0 years, 276 female, IFN-monotherapy: n = 19,
      IFN/RBV: n = 122, peg-IFN/RBV: n = 573, SVR: 551, non-SVR: 163) were studied. Two
      hundred and ten of 540 patients with a liver biopsy prior to treatment had
      advanced stages of fibrosis (Metavir F3/F4). RESULTS: Forty-eight patients died
      during follow-up, 15 with SVR and 33 without (P < 0.001). Five- and 10-year
      mortality rates were 1.8% (10/551) and 2.7% (15/551) in the SVR group and 8.6%
      (14/163) and 19.1% (31/163) in the non-SVR patients (P < 0.001). In 29 patients,
      decompensation of liver disease [SVR: 9 (1.6%) vs. non-SVR: 20 (12.3%); P <
      0.001] occurred and in 29 patients, HCC developed during follow-up [SVR: 10
      (1.8%) vs. non-SVR: 19 (11.7%); P < 0.001]. Non-SVR was an independent predictor
      for developing (i) HCC [HR: 2.36 (95% CI: 1.07-5.23; P = 0.034], (ii) liver
      related complications [HR: 2.62; (95% CI: 1.18-5.81; P = 0.018] and (iii)
      mortality (HR: 3.46; 95% CI: 1.91-6.29; P < 0.001). For patients with early
      stages of fibrosis (F0-F2), a survival benefit of SVR patients could not be
      demonstrated. CONCLUSIONS: Successful anti-viral therapy decreases mortality,
      incidence of hepatocellular carcinoma and liver failure in patients with advanced
      fibrosis. However, hepatocellular carcinoma development or liver failure are not
      prevented completely, and further follow-up of patients is advisable.

PMID- 25616018
TI  - Fatty infiltration of the thymus in response to illness in the pediatric
      population.
AB  - Under physiologic stress, glucocorticoids contribute to thymic involution. While
      steroids enhance fatty infiltration, this change has not been well studied in the
      pediatric thymus during illness. Evaluation of 130 thymuses from fetuses, infants
      and children determined the frequency of thymic fatty infiltration to be low
      (25%), particularly in fetal thymus (4%). In most cases, fatty infiltration was
      focal. There was a significant correlation with duration of illness, but not with
      patient age, gestational age, or underlying disease. There was significantly less
      fatty infiltration in fetal thymus compared to post-natal thymus, for the same
      degree of thymic involution. Only seven cases showed diffuse thymic fatty
      infiltration; all were post-natal associated with an infectious etiology. In
      contrast, fetal cases of chorioamnionitis seldom showed fatty infiltration and
      only focally, implying the stress response of fetal thymus differs post-natal,
      possibly related to the timing of adipose tissue development and fetal
      glucocorticoid response to stress. 

PMID- 25616019
TI  - Shaken Baby Syndrome: a review.
AB  - Shaken Baby Syndrome occurs in infants as a result of the brain pushing against
      the skull due to severe acceleration-deceleration forces. Symptoms of Shaken Baby
      Syndrome include subdural, subarachnoid, and retinal hemorrhages. MRI and ocular
      examinations are used to determine the extent of mental and visual damage and
      beta-amyloid precursor protein immunohistochemical staining is used to detect
      axonal injuries. Surgeries such as Subdural hemorrhage (SDH) evacuation surgery
      and the Burr hole craniotomy are used to treat Shaken Baby Syndrome; however, the
      prognosis is poor in many cases. Because of the severity of Shaken Baby Syndrome
      and its traumatic and sometimes fatal effects, it is important to educate new
      parents, nurses, and doctors on the syndrome in order to prevent incidents. 

PMID- 25616020
TI  - Can neonatal hepatitis be more fatal than biliary atresia?
AB  - BACKGROUND/AIMS: The basic problem in diagnosis of neonatal cholestasis (NC) is
      to differentiate biliary atresia (BA) from other non-obstructive disorders.
      Because if bile flow cannot be provided by surgery, BA leads to cirrhosis and
      death within the first year of life. The aim of the present study is to determine
      histopathological features that may help to differentiate BA from neonatal
      hepatitis (NH). MATERIAL AND METHODS: This retrospective study was carried out on
      105 liver biopsy specimens of 74 infants with NC who were diagnosed between 2003
      and 2012. RESULTS: The mean age was 76.5 +/- 40.64 days. The most valuable biopsy
      findings for the discrimination between NH and BA, in decreasing order of
      importance, were ductular proliferation (p < 0.001), cholestasis in neoductuli (p
      < 0.001), fibrosis (p = 0.002), and extramedullar hematopoiesis (p = 0.02). While
      Kasai operations were performed in 19 cases, liver transplantation was performed
      in 10 cases. Survival rate among the death cases with BA was longer than the
      survival time of the death cases with NH (p = 0.023). Currently more children
      live with a close to normal quality of life with portoenterostomy and/or liver
      transplantation. On the contrary, NH can be more fatal with associated disorders
      such as growth retardation, specific infections, respiratory distress, and
      metabolic or endocrine diseases.

PMID- 25616021
TI  - Neuroblastoma in Children Under 12 Months in Singapore--15-Year Experience and
      Outcomes From KKH.
AB  - BACKGROUND: Expectant observation of small adrenal lesions has shown promising
      results in recent studies. We present our 15 years outcome of managing infant
      neuroblastoma. METHODS: All patients with neuroblastoma below the age of 1 year
      treated at the largest pediatric hospital in Singapore between 1998 and 2012 were
      identified. RESULTS: Twenty-two patients were included in our study. Six were
      antenatally diagnosed. Nineteen (86%) patients had surgical resection of the
      tumor. Eight (36%) patients received chemotherapy as part of their treatment. Six
      patients were observed three of which had large adrenal tumors. Median follow-up
      in our series was 2.6 years. The 5 year overall survival was 90%. There were no
      recurrences and there were 2 deaths in our series. CONCLUSION: Our series shows
      excellent outcomes of infant neuroblastoma at our center. Careful observation of
      large tumors may be an option to avoid the morbidity of surgery.

PMID- 25616022
TI  - Silicon phthalocyanine covalently functionalized N-doped ultrasmall reduced
      graphene oxide decorated with Pt nanoparticles for hydrogen evolution from water.
AB  - To improve the photocatalytic activity of graphene-based catalysts, silicon
      phthalocyanine (SiPc) covalently functionalized N-doped ultrasmall reduced
      graphene oxide (N-usRGO) has been synthesized through 1,3-dipolar cycloaddition
      of azomethine ylides. The obtained product (N-usRGO/SiPc) was characterized by
      transmission electron microscopy, atomic force microscopy, Fourier transform
      infrared spectroscopy, Raman spectra, X-ray photoelectron spectroscopy,
      fluorescence, and UV-vis spectroscopy. The results demonstrate that SiPc has been
      successfully grafted on the surface of N-usRGO. The N-usRGO/SiPc nanocomposite
      exhibits high light-harvesting efficiency covering a range of wavelengths from
      the ultraviolet to visible light. The efficient fluorescence quenching and the
      enhanced photocurrent response confirm that the photoinduced electron transfers
      from the SiPc moiety to the N-usRGO sheet. Moreover, we chose Pt nanoparticles as
      cocatalyst to load on N-usRGO/SiPc sheets to obtain the optimal H2 production
      effect. The platinized N-usRGO/SiPc (N-usRGO/SiPc/Pt) demonstrates good hydrogen
      evolution performance under both UV-vis and visible light (lambda>400 nm)
      irradiation. The apparent quantum yields are 1.3% and 0.56% at 365 and 420 nm,
      respectively. These results reveal that N-usRGO/SiPc/Pt nanocomposite,
      consolidating the advantages of SiPc, N-usRGO, and Pt NPs, can be a potential
      candidate for hydrogen evolution from water under UV-vis or visible light
      irradiation. 

PMID- 25616023
TI  - Monitoring eating habits using a piezoelectric sensor-based necklace.
AB  - Maintaining appropriate levels of food intake and developing regularity in eating
      habits is crucial to weight loss and the preservation of a healthy lifestyle.
      Moreover, awareness of eating habits is an important step towards portion control
      and weight loss. In this paper, we introduce a novel food-intake monitoring
      system based around a wearable wireless-enabled necklace. The proposed necklace
      includes an embedded piezoelectric sensor, small Arduino-compatible
      microcontroller, Bluetooth LE transceiver, and Lithium-Polymer battery. Motion in
      the throat is captured and transmitted to a mobile application for processing and
      user guidance. Results from data collected from 30 subjects indicate that it is
      possible to detect solid and liquid foods, with an F-measure of 0.837 and 0.864,
      respectively, using a naive Bayes classifier. Furthermore, identification of
      extraneous motions such as head turns and walking are shown to significantly
      reduce the false positive rate of swallow detection. 

PMID- 25616024
TI  - Mass spectrometry cleavable strategy for identification and differentiation of
      prenylated peptides.
AB  - Prenylation of protein (farnesylation and geranylgeranylation) is involved in
      several human cancers, such as pancreatic, colon, and acute myeloid leukemia as
      well as Hutchinson-Gilford progeria syndrome (HGPS), a genetic disease that is
      associated with premature aging for children. Current biochemical methods are not
      very efficient in identifying and differentiating large-scale prenylations in
      vivo or in vitro. There are limited methods available for large-scale detection
      of prenylated proteins using mass spectrometry and no methods currently available
      which can distinguish farnesylation and geranylgeranylation modification in a
      single experimental setup. In this study, a simple and novel method for detection
      and distinction of large-scale prenylated peptides using mass spectrometry
      cleavable approaches was developed. The method utilizes simple chemistry on the
      prenyl group and cleavable properties of a sulfoxide group in the gas phase to
      produce a signature mass spectrum during tandem mass spectrometric events. The
      characteristic masses lost from the modified prenylated peptides distinguished
      the types of prenylation. We also introduced epoxy groups in the prenylation
      sites of the proteins to make them more hydrophilic and enrichable from complex
      samples. Stability of the epoxide group was also studied under liquid
      chromatography-mass spectrometry (LC-MS) conditions. The proof-of-concept of this
      method was established using prenylated peptides which mimicked the prenyl motifs
      in the proteins. We believe this method will advance the identification and
      differentiation of the types of prenylation in proteins in large-scale studies
      and will improve significantly our knowledge of the mechanism of cancer, cancer
      treatments, and diagnosis. 

PMID- 25616025
TI  - Baclofen-induced encephalopathy in an older patient with stage 2 chronic kidney
      disease.

PMID- 25616026
TI  - Maternal vitamin D and E intakes during early pregnancy are associated with
      airway epithelial cell responses in neonates.
AB  - BACKGROUND: Antenatal factors including maternal diet may predispose to airway
      disease, possibly by impacting on fetal airway development. OBJECTIVE: This
      cohort study tested the hypothesis that maternal vitamin D and E status in early
      pregnancy is associated with airway epithelial cell (AEC) responses in new born
      infants and examined constitutive and TNFalpha/IL-1beta, house dust mite (HDM)
      extract or lipopolysaccharide (LPS)-stimulated neonatal AEC responses in vitro.
      METHODS: Maternal dietary vitamin D and E intakes (plasma 25[OH]D3 or alpha
      tocopherol) were characterized at 10-12 weeks gestation. Neonatal nasal AECs were
      collected soon after birth and cultured to tertiary passage. Constitutive and
      stimulated - TNFalpha/IL-1beta, HDM extract or LPS - secretory responses (VEGF,
      RANTES, MCP-1, IL-17A, IFN-gamma, GM-CSF, eotaxin, MIP1-alpha, MIP1-beta, ICAM,
      IL-6, IL-8, IL-10, TNF) in 139 AEC cultures were quantified. RESULTS: AEC
      mediator release was greater following TNF-alpha/IL-1beta, HDM or LPS stimulation
      compared to constitutive release. Increased maternal dietary vitamin D was
      associated with significant increases in IL-10 release by AEC after stimulation
      with TNF-alpha/IL-1beta (P = 0.024) or HDM (P = 0.049). Maternal plasma alpha
      tocopherol at 10-12 weeks gestation was positively associated with MIP1alpha
      (Spearman's rho 0.242, P = 0.009) and IL-3 (rho 0.189, P = 0.043) responses after
      TNF-alpha/IL-1beta stimulation and negatively associated with TNF (rho -0.404, P
      = 0.011) and MIP1beta (rho -0.322, P = 0.046) responses after LPS stimulation.
      DISCUSSION: Neonatal AECs respond to pro-inflammatory and allergenic stimuli in
      vitro demonstrating their potential to function as components of the innate
      immune response. Our findings suggest that associations exist between maternal
      micronutrient intake during early pregnancy and aspects of stimulated neonatal
      airway epithelial cell secretory function that may in turn impact on the
      development of asthma and/or allergic rhinitis in later life.

PMID- 25616027
TI  - Enhancing photo-catalytic production of organic acids in the cyanobacterium
      Synechocystis sp. PCC 6803 DeltaglgC, a strain incapable of glycogen storage.
AB  - A key objective in microbial biofuels strain development is to maximize carbon
      flux to target products while minimizing cell biomass accumulation, such that
      ideally the algae and bacteria would operate in a photo-catalytic state. A brief
      period of such a physiological state has recently been demonstrated in the
      cyanobacterium Synechocystis sp. PCC 6803 DeltaglgC strain incapable of glycogen
      storage. When deprived of nitrogen, the DeltaglgC excretes the organic acids
      alpha-ketoglutarate and pyruvate for a number of days without increasing cell
      biomass. This study examines the relationship between the growth state and the
      photo-catalytic state, and characterizes the metabolic adaptability of the photo
      catalytic state to increasing light intensity. It is found that the culture can
      transition naturally from the growth state into the photo-catalytic state when
      provided with limited nitrogen supply during the growth phase. Photosynthetic
      capacity and pigments are lost over time in the photo-catalytic state. Reversal
      to growth state is observed with re-addition of nitrogen nutrient, accompanied by
      restoration of photosynthetic capacity and pigment levels in the cells. While the
      overall productivity increased under high light conditions, the ratio of alpha
      ketoglutarate/pyruvate is altered, suggesting that carbon partition between the
      two products is adaptable to environmental conditions. 

PMID- 25616028
TI  - Accuracy and Reproducibility of High-definition Anorectal Manometry and Pressure
      Topography Analyses in Healthy Subjects.
AB  - BACKGROUND & AIMS: High-definition anorectal manometry (HDAM-3D) provides a
      topographic and 3-dimensional profile of anorectal pressure. We assessed
      anorectal sensorimotor function and the reproducibility of measurements made with
      HDAM-3D in healthy adults, and the accuracy of data analysis by its software.
      METHODS: Anal sphincter pressures and rectal sensory thresholds were measured in
      78 healthy subjects via placement of a 10-mm rigid probe, with 256
      circumferentially arrayed pressure sensors, and a balloon in the rectum. The
      bearing down maneuver was assessed in a subset of 18 subjects. We compared data
      analyzed by an expert with findings from automated software analysis.
      Measurements made in a subset of 16 subjects, 2 weeks apart, were compared to
      determine reproducibility. RESULTS: Resting, squeezing, and sustained squeezing
      pressures were significantly higher in men than in women (P < .05); other
      parameters were similar. Desire and urgency to defecate were similar between men
      and women, but the maximal tolerable volume was significantly lower in women (P <
      .05). Older women (>50 years) had significantly lower resting (P < .01) and
      sustained squeeze pressures (P < .04). Dyssynergic patterns of defecation were
      observed in 12 of 18 subjects (67%) who attempted to defecate without the 60-mL
      rectal balloon distention and in 6 of 18 subjects (33%) with the 60-mL rectal
      balloon distention. Test-retest values correlated (r = 0.81), as did analyses
      made by an expert vs software analyses of data (r = 0.99). CONCLUSIONS: On the
      basis of HDAM-3D measurements in healthy adults, anal sphincter pressures are
      higher in men than in women, but sensory and other parameters are similar; older
      subjects have weaker sphincters. Many people were found to have dyssynergic
      patterns of defecation, which could be related to the probe or other technical
      issues, so this technique may not be suitable for assessing defecation patterns.
      Measurements made by HDAM-3D are reproducible, and data can be accurately
      analyzed by its software.

PMID- 25616029
TI  - Development and validation of a scoring system to identify patients with
      microscopic colitis.
AB  - BACKGROUND & AIMS: Diarrhea is a common indication for colonoscopy. Biopsies are
      collected and analyzed from patients with a macroscopically normal colon to
      exclude microscopic colitis (MC), but the diagnostic yield is low because most
      patients have functional disease. We developed and validated a diagnostic scoring
      system to identify patients with MC to reduce the need to collect biopsies from
      all patients. METHODS: We performed a retrospective study, which analyzed
      demographic and symptom data from adult patients with chronic diarrhea evaluated
      by colonoscopy and biopsy at 3 endoscopy centers in Leeds, United Kingdom. To
      derive the scoring system, we analyzed data from 476 adult patients (mean age,
      53.6 years; 63.7% female) examined in 2011. Factors significantly associated with
      the presence of MC were assigned item scores, and total scores were determined
      for each patient. To validate the system, we used it to assess data from 460
      patients (mean age, 52.9 years; 59.8% female) examined in 2012. The primary aim
      of the study was to determine the performance of the diagnostic scoring system in
      identifying patients with MC by using histologic findings as a reference.
      RESULTS: In the derivation cohort, 85 patients were diagnosed with MC on the
      basis of histologic analysis. Age >=50 years, female sex, use of proton pump
      inhibitors or nonsteroidal anti-inflammatory drugs, weight loss, and absence of
      abdominal pain were significantly associated with MC. We created a scoring system
      for diagnosis of MC, with scores ranging from -8 to +38; scores >=8 were used to
      identify the presence of MC. This cutoff value identified patients with MC in the
      validation cohort (74 patients, 16.1%) with 90.5% sensitivity and 45.3%
      specificity (area under the receiver operating characteristic curve value, 0.76).
      Because of its ability to exclude MC and therefore avoid the need for routine
      collection of colonic biopsies, this scoring system reduced the cost of
      evaluation by >L7000 in the cohort. CONCLUSIONS: We collected data on risk
      factors for MC to create a scoring system that identifies patients with MC with
      more than 90% sensitivity. This system can also reduce costs by identifying
      patients who are unlikely to have MC who do not require biopsy analysis.

PMID- 25616030
TI  - Sesquiterpene lactones of Moquiniastrum polymorphum subsp. floccosum have
      antineoplastic effects in Walker-256 tumor-bearing rats.
AB  - BACKGROUND AND AIM: This study aimed to evaluate the in vivo antitumor actions
      and toxicity of the dichloromethane fraction (F1B) of Moquiniastrum polymorphum
      subsp. floccosum (formerly Gochnatia polymorpha ssp. floccosa), composed of
      sesquiterpene lactones, against Walker-256 carcinosarcoma in rats. METHODS: Male
      Wistar rats received 100 mg kg(-1) F1B per day orally for 16 days after
      subcutaneous inoculation of Walker-256 cells in the pelvic limb. The tumor
      progression was monitored, and after treatment, tumor weight, oxidative stress,
      plasma biochemistry, inflammatory parameters, gene expression and histology of
      tumor and/or liver were evaluated. The toxicity of F1B was analyzed through the
      relative weight of organs. Additionally, an LD50 test was performed in mice.
      RESULTS: F1B treatment significantly reduced tumor volume and weight. There was
      no difference in oxidative stress in tumor tissue after treatment. F1B treatment
      modified hepatic glutathione and superoxide dismutase, and normalized plasma
      glucose, alkaline phosphatase, and amylase. F1B did not affect the activity of
      myeloperoxidase and N-acetylglucosaminidase or the nitric oxide levels in tumor
      tissue. However, F1B decreased the tumor necrosis factor (TNF)-alpha levels.
      Additionally, F1B increased apoptosis in the tumor, mediated by up-regulation of
      the p53 and Bax gene expression. No clinical signs of toxicity or death were
      observed in the rats treated with F1B. The LD50 calculated for mice was 1209 mg
      kg(-1). CONCLUSIONS: F1B, which is rich in sesquiterpene lactones, showed
      antitumor activity against Walker-256 carcinosarcoma. This effect may be, at
      least in part, related to the induction of apoptosis and inhibition of TNF-alpha
      signaling.

PMID- 25616032
TI  - The relation between speed environment, age and injury outcome for bicyclists
      struck by a motorized vehicle - a comparison with pedestrians.
AB  - This study analyzes (a) the relation between injury severities, the age of the
      bicyclist and the speed environment at accident locations (mean travel speed of
      the traffic flow involved in the accident) where a bicyclist was struck by a
      motorized vehicle and (b) how these relations differ from those for struck
      pedestrians. Accident data from Sweden for the years 2004-2008 was used to
      identify accident locations to analyze the relations between speed environment,
      age and injury outcome. Seventy-seven accident sites were used for field
      measurements and further analysis. The results show that both speed environment
      and age have considerable correlation with injury severity. There was a
      statistically significant relation between injury severity and the speed
      environment, and large proportion of the serious bicycle accidents occur at
      locations with speeds below 30km/h. Also, the risk of serious injuries or
      fatalities seems to increase after the age of 45. To our knowledge this is the
      first study that uses the mean travel speed in this manner for analyzing injury
      severity of struck bicyclists. 

PMID- 25616031
TI  - Bupropion-varenicline interactions and nicotine self-administration behavior in
      rats.
AB  - Varenicline and bupropion each have been shown to significantly improve cessation
      of tobacco addiction in humans. They act through different mechanisms and the
      question about the potential added efficacy with their combined used has arisen.
      Preclinical animal models of nicotine addiction can help with the evaluation of
      this combined approach and what dose combinations of varenicline and bupropion
      may be useful for enhancing tobacco cessation. In this study, we investigated the
      interacting dose-effect functions of varenicline and bupropion in a rat model of
      nicotine self-administration. Young adult female Sprague-Dawley rats were allowed
      to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule.
      Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were
      administered alone or together 15 min before each session. The vehicle saline was
      the control. Higher doses of each drug alone reduced nicotine self-administration
      compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and
      75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself
      reduce nicotine self-administration, significantly augmented bupropion effects.
      The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses
      caused greater reductions of nicotine self-administration than either dose of
      bupropion given alone. However, higher dose varenicline did not have this effect.
      Lower dose bupropion did not augment varenicline effects. Only the high bupropion
      dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg
      varenicline with 75 mg/kg bupropion reduced self-administration to a greater
      extent than either dose alone. These results demonstrate that combination therapy
      with varenicline and bupropion may be more beneficial than monotherapy with
      either drug alone.

PMID- 25616033
TI  - Development of crash modification factors for changing lane width on roadway
      segments using generalized nonlinear models.
AB  - This study evaluates the effectiveness of changing lane width in reducing crashes
      on roadway segments. To consider nonlinear relationships between crash rate and
      lane width, the study develops generalized nonlinear models (GNMs) using 3-years
      crash records and road geometry data collected for all roadway segments in
      Florida. The study also estimates various crash modification factors (CMFs) for
      different ranges of lane width based on the results of the GNMs. It was found
      that the crash rate was highest for 12-ft lane and lower for the lane width less
      than or greater than 12ft. GNMs can extrapolate this nonlinear continuous effect
      of lane width and estimate the CMFs for any lane width, not only selected lane
      widths, unlike generalized linear models (GLMs) with categorical variables. The
      CMFs estimated using GNMs reflect that crashes are less likely to occur for
      narrower lanes if the lane width is less than 12ft whereas crashes are less
      likely to occur for wider lanes if the lane width is greater than 12ft. However,
      these effects varied with the posted speed limits as the effect of interaction
      between lane width and speed limit was significant. The estimated CMFs show that
      crashes are less likely to occur for lane widths less than 12ft than the lane
      widths greater than 12ft if the speed limit is higher than or equal to 40mph. It
      was also found from the CMFs that crashes at higher severity levels (KABC and
      KAB) are less likely to occur for lane widths greater or less than 12ft compared
      to 12-ft lane. The study demonstrates that the CMFs estimated using GNMs clearly
      reflect variations in crashes with lane width, which cannot be captured by the
      CMFs estimated using GLMs. Thus, it is recommended that if the relationship
      between crash rate and lane width is nonlinear, the CMFs are estimated using
      GNMs. 

PMID- 25616034
TI  - The intrarenal generation of angiotensin II is required for experimental
      hypertension.
AB  - Hypertension is a major risk factor for cardiovascular disease. While the cause
      of hypertension is multifactorial, renal dysregulation of salt and water
      excretion is a major factor. All components of the renin-angiotensin system are
      produced locally in the kidney, suggesting that intrarenal generation of
      angiotensin II plays a key role in blood pressure regulation. Here, we show that
      two mouse models lacking renal angiotensin converting enzyme (ACE) are protected
      against angiotensin II and l-NAME induced hypertension. In response to
      hypertensive stimuli, mice lacking renal ACE do not produce renal angiotensin II.
      These studies indicate that the intrarenal renin-angiotensin system works as an
      entity separate from systemic angiotensin II generation. Renal ACE appears
      necessary for experimental hypertension. 

PMID- 25616035
TI  - Regulation of renal function and blood pressure control by P2 purinoceptors in
      the kidney.
AB  - Kidneys are important regulators of extracellular fluid volume (ECFV)
      homeostasis. ECFV is a key regulatory component of long-term blood pressure
      control influenced by controlling tubular sodium transport. In recent decades,
      renal P2 purinoceptors (P2 receptors) have come to the forefront as a mechanism
      for regulating ECFV. P2 receptors are broadly distributed in renal tubular and
      vascular elements where they confer segmental control of renal vascular
      resistance, autoregulation, and tubular reabsorption. Activation or impairment of
      renal P2 purinoceptors is implicated in the regulating blood pressure or causing
      renal pathologies including hypertension. In this brief review, we discuss the
      role of renal vascular and tubular P2 purinoceptors in the regulation of renal
      hemodynamics, maintenance of ECFV, regulation of sodium reabsorption and the
      control of blood pressure. 

PMID- 25616036
TI  - Completely stereocontrolled aldol reaction of chiral beta-amino acids.
AB  - A general protocol to independently access stereoisomerically pure beta'-hydroxy
      beta-amino acid derivatives that is based on dibutylboron triflate-mediated aldol
      reaction of suitably protected beta-amino acids bearing chiral oxazolidinone
      auxiliary is reported. The method smoothly afforded syn-aldol (alpha,beta'-syn)
      products in pure form and excellent isolated yield. Both alpha,beta-syn and
      alpha,beta-anti isomers are readily accessible solely through the choice of the
      oxazolidinone chirality. This method allows for the preparation of stereoisomeric
      beta'-hydroxy-beta-amino acid derivatives that were previously unreported. 

PMID- 25616037
TI  - Peroxisomes: a small step from mitochondria but a giant leap for eukaryotes.

PMID- 25616043
TI  - Microscopic view on the ultrafast photoluminescence from photoexcited graphene.
AB  - We present a joint theory-experiment study on ultrafast photoluminescence from
      photoexcited graphene. On the basis of a microscopic theory, we reveal two
      distinct mechanisms behind the occurring photoluminescence: besides the well
      known incoherent contribution driven by nonequilibrium carrier occupations, we
      found a coherent part that spectrally shifts with the excitation energy. In our
      experiments, we demonstrate for the first time the predicted appearance and
      spectral shift of the coherent photoluminescence. 

PMID- 25616042
TI  - Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation
      in sickle cell pain crisis.
AB  - Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium
      and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso
      occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients
      admitted with pain crisis, we evaluated the status of adhesion molecules on
      neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800
      mg/kg, the same dose used in murine studies. Mac-1 function significantly
      decreased from baseline in the low-dose IVIG (200-400 mg/kg) cohorts. IVIG
      related adverse events may have occurred in the high-dose (600-800 mg/kg)
      cohorts. There were no significant increases in neutrophil and leukocyte counts,
      suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to
      neutrophil adhesion. This study provides the first in-human validation of pre
      clinical murine studies that IVIG can decrease Mac-1 function.

PMID- 25616048
TI  - Genetic variability of the S segment of Toscana virus.
AB  - Toscana virus (TOSV) was originally isolated in 1971 from a pool of Phlebotomus
      perniciosus sandflies collected in Grosseto province (Central Italy). Since its
      first isolation, several studies have been conducted in Italy and other
      Mediterranean countries in order to identify its possible animal reservoirs,
      spread of infection and genetic variability. Phylogenetic analysis conducted on
      TOSV genome demonstrated the co-circulation of two major lineages in the
      Mediterranean areas, TOSV A and TOSV B. This study reports the results of the
      genetic analysis of 32 viral strains isolated in Italy in the last 30 years from
      patients hospitalized with neurological disease, from sandflies and from the
      brain of a bat. The genetic diversity of TOSV was investigated by determining the
      sequences of the whole S segment. Phylogenetic analysis showed that TOSV A
      lineage represents the lineage circulating in Italy. Moreover, the current
      variability of lineage A is similar to that of lineage B. 

PMID- 25616049
TI  - Molecular epidemiology of Aleutian mink disease virus (AMDV) in Estonia, and a
      global phylogeny of AMDV.
AB  - Aleutian mink disease virus (AMDV) causes a severe disease called Aleutian
      disease (AD). AMDV infects primarily mustelids, but also other mammal species.
      Recent evidence suggests that AMDV may also affect humans. To examine AMDV in
      different wild animals and in farmed mink in Estonia, we collected 203 blood
      samples from eight mammal species in 2007-2010, of which 152 were from species
      living in the wild (American mink, European mink, pine marten, polecat, raccoon
      dog, badger, otter, and stone marten) and 51 were from farmed mink. AMDV was
      tested by PCR amplification of NS1 and VP2 gene fragments, and was only detected
      in 4 free-ranging (14.8%) and 11 farmed (21.6%) American mink. No other species
      was positive for AMDV. In addition, the VP2 gene fragment was sequenced for 14
      farmed mink isolates from Finland for which NS1 sequences were already publicly
      available. None of the four Estonian AMDV isolates found in free-ranging mink had
      identical sequences with farmed mink. In fact, isolates from free-ranging and
      farmed mink belonged to different clades, suggesting that the analyzed virus
      isolates circulating in nature are not from escapees of current farms. Two global
      phylogenies were built: one based on NS1 (336 bp, 151 taxa from nine countries);
      the other based on a combined NS1-VP2 dataset (871 bp, 40 taxa from six
      countries). AMDV genotypes did not cluster according to their geographic origin,
      suggesting that transport of farm mink from multiple source farms has been
      intense. Nevertheless, one subclade in both phylogenies was comprised solely of
      isolates from farmed mink, while several subclades comprised isolates only from
      free-ranging mink, indicating that some isolates may circulate more in the wild
      and others among farm animals.

PMID- 25616050
TI  - Full genome sequence analysis of a wild, non-MLV-related type 2 Hungarian PRRSV
      variant isolated in Europe.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a widespread
      pathogen of pigs causing significant economic losses to the swine industry. The
      expanding diversity of PRRSV strains makes the diagnosis, control and eradication
      of the disease more and more difficult. In the present study, the authors report
      the full genome sequencing of a type 2 PRRSV strain isolated from piglet
      carcasses in Hungary. Next generation sequencing was used to determine the
      complete genome sequence of the isolate (PRRSV-2/Hungary/102/2012). Recombination
      analysis performed with the available full-length genome sequences showed no
      evidence of such event with other known PRRSV. Unique deletions and an insertion
      were found in the nsp2 region of PRRSV-2/Hungary/102/2012 when it was compared to
      the highly virulent VR2332 and JXA-1 prototype strains. The majority of amino
      acid alterations in GP4 and GP5 of the virus were in the known antigenic regions
      suggesting an important role for immunological pressure in PRRSV
      2/Hungary/102/2012 evolution. Phylogenetic analysis revealed that it belongs to
      lineage 1 or 2 of type 2 PRRSV. Considering the lack of related PRRSV in Europe,
      except for a partial sequence from Slovakia, the ancestor of PRRSV
      2/Hungary/102/2012 was most probably transported from North-America. It is the
      first documented type 2 PRRSV isolated in Europe that is not related to the
      Ingelvac MLV. 

PMID- 25616051
TI  - Engineering metabolism through dynamic control.
AB  - Metabolic engineering has proven crucial for the microbial production of valuable
      chemicals. Due to the rapid development of tools in synthetic biology, there has
      been recent interest in the dynamic regulation of flux through metabolic pathways
      to overcome some of the issues arising from traditional strategies lacking
      dynamic control. There are many diverse implementations of dynamic control, with
      a range of metabolite sensors and inducers being used. Furthermore, control has
      been implemented at the transcriptional, translational and post-translational
      levels. Each of these levels have unique sets of engineering tools, and allow for
      control at different dynamic time-scales. In order to extend the applications of
      dynamic control, new tools are required to improve the dynamics of regulatory
      circuits. Further study and characterization of circuit robustness is also needed
      to improve their applicability to industry. The successful implementation of
      dynamic control, using technologies that are amenable to commercialization, will
      be a fundamental step in advancing metabolic engineering. 

PMID- 25616052
TI  - Determination of Singlet Oxygen and Electron Transfer Mediated  Mechanisms of
      Photosensitized Protein Damage by  Phosphorus(V)porphyrins.
AB  - The mechanism of photosensitized protein damage byphosphorus(V)
      tetraphenylporphyrin derivatives (P(V)TPPs) wasquantitatively clarified. P(V)TPPs
      bound to human serum albumin(HSA), a water-soluble protein, and damaged its
      tryptophan residueduring photoirradiation. P(V)TPPs photosensitized singlet
      oxygen ((1)O(2))generation, and the contribution of (1)O(2) to HSA damage was
      confirmedby the inhibitory effect of sodium azide, a (1)O(2) quencher.
      However,sodium azide could not completely inhibit HSA damage, suggesting
      thecontribution of an electron transfer mechanism to HSA damage. Thedecrement in
      the fluorescence lifetime of P(V)TPPs by HSA supportedthe electron transfer
      mechanism. The contribution of these processes could be determined by the kinetic
      analysis of the effect ofsodium azide on the photosensitized protein damage by
      P(V)TPPs.

PMID- 25616053
TI  - Discrete Versus Continuous Mapping of Facial Electromyography for Human-Machine
      Interface Control: Performance and Training Effects.
AB  - Individuals with high spinal cord injuries are unable to operate a keyboard and
      mouse with their hands. In this experiment, we compared two systems using surface
      electromyography (sEMG) recorded from facial muscles to control an onscreen
      keyboard to type five-letter words. Both systems used five sEMG sensors to
      capture muscle activity during five distinct facial gestures that were mapped to
      five cursor commands: move left, move right, move up, move down, and "click". One
      system used a discrete movement and feedback algorithm in which the user produced
      one quick facial gesture, causing a corresponding discrete movement to an
      adjacent letter. The other system was continuously updated and allowed the user
      to control the cursor's velocity by relative activation between different sEMG
      channels. Participants were trained on one system for four sessions on
      consecutive days, followed by one crossover session on the untrained system.
      Information transfer rates (ITRs) were high for both systems compared to other
      potential input modalities, both initially and with training (Session 1: 62.1
      bits/min, Session 4: 105.1 bits/min). Users of the continuous system showed
      significantly higher ITRs than the discrete users. Future development will focus
      on improvements to both systems, which may offer differential advantages for
      users with various motor impairments. 

PMID- 25616054
TI  - Aerosol Route to Administer Teicoplanin in Mechanical Ventilation: In Vitro
      Study, Lung Deposition and Pharmacokinetic Analyses in Pigs.
AB  - BACKROUND: Glycopeptides given intravenously achieve low airway concentrations.
      Nebulization of teicoplanin may be an efficient way of delivering a high
      concentration of this antibiotic to the lung. This multistep study assessed the
      feasibility of teicoplanin nebulization during mechanical ventilation by
      evaluating: the stability of its antibiotic effect; epithelial tolerance; lung
      deposition and systemic absorption in ventilated pigs. METHODS: Nebulized and non
      nebulized teicoplanin activity was tested on Staphylococcus aureus cultures. The
      cytotoxic effect of teicoplanin on human respiratory epithelial cells was
      assessed by measuring lactate dehydrogenase activity released, cell viability,
      and transepithelial electrical resistance. Volume median diameter of particles of
      nebulized teicoplanin was measured by laser diffraction during mechanical
      ventilation. The deposited mass of teicoplanin nebulized with a vibrating mesh
      nebulizer in ventilated piglets was assessed by scintigraphy. Blood
      pharmacokinetics of teicoplanin administered either intravenously or by
      nebulization was compared. RESULTS: No decrease of antibiotic activity was
      observed after nebulization. In vitro cytotoxicity of teicoplanin was only
      observed with 1000 times the dose recommended for intravenous administration.
      Volume median diameter of particles was 2.5+/-0.1 MUm. Of the initial nebulizer
      charge of teicoplanin, 24+/-7% was present in the lungs of ventilated pigs after
      the nebulization. Amount absorbed in blood was low (3.4%+/-0.9%) after
      nebulization, and blood stream elimination half-life value was 25.4 h.
      CONCLUSIONS: Teicoplanin was administered efficiently by nebulization during
      mechanical ventilation, without any effect on its pharmacological properties or
      any cytotoxicity. The pharmacokinetic parameters are promising in view of its
      time-dependent killing process. All the results of our multi-step study
      highlighted the potential of teicoplanin to be nebulized during mechanical
      ventilation.

PMID- 25616056
TI  - Ground beef patties prepared from brisket, flank and plate have unique fatty acid
      and sensory characteristics.
AB  - We hypothesized that unique ground beef products could be formulated from
      brisket, flank, and plate primals. Primals were taken from 4 USDA Select
      carcasses from conventionally produced cattle, selected at random in a commercial
      packing plant. Lean and fat trims were separated, and ground beef was formulated
      from each primal to contain 10, 20, or 30% total fat. Brisket patties contained
      higher proportions of monounsaturated fatty acids and less saturated fatty acids
      than flank patties. There were no differences in n-6 or n-3 fatty acids across
      primal type or fat level. After cooking, brisket patties had higher bloody/serumy
      and fat-like descriptor values than flank patties. Plate patties generated higher
      amounts of lipid-derived volatiles than patties from the brisket or flank.
      Brisket patties generally had higher amounts of pleasant headspace volatiles
      whereas the plate relied more heavily on Maillard-derived volatiles than flank
      patties. We conclude that individual primals can be used to formulate ground beef
      with unique compositional and flavor characteristics. 

PMID- 25616055
TI  - Evolving robust gene regulatory networks.
AB  - Design and implementation of robust network modules is essential for construction
      of complex biological systems through hierarchical assembly of 'parts' and
      'devices'. The robustness of gene regulatory networks (GRNs) is ascribed chiefly
      to the underlying topology. The automatic designing capability of GRN topology
      that can exhibit robust behavior can dramatically change the current practice in
      synthetic biology. A recent study shows that Darwinian evolution can gradually
      develop higher topological robustness. Subsequently, this work presents an
      evolutionary algorithm that simulates natural evolution in silico, for
      identifying network topologies that are robust to perturbations. We present a
      Monte Carlo based method for quantifying topological robustness and designed a
      fitness approximation approach for efficient calculation of topological
      robustness which is computationally very intensive. The proposed framework was
      verified using two classic GRN behaviors: oscillation and bistability, although
      the framework is generalized for evolving other types of responses. The algorithm
      identified robust GRN architectures which were verified using different analysis
      and comparison. Analysis of the results also shed light on the relationship among
      robustness, cooperativity and complexity. This study also shows that nature has
      already evolved very robust architectures for its crucial systems; hence
      simulation of this natural process can be very valuable for designing robust
      biological systems. 

PMID- 25616057
TI  - Transaction cost analysis of in-clinic versus telehealth consultations for
      chronic pain: preliminary evidence for rapid and affordable access to
      interdisciplinary collaborative consultation.
AB  - OBJECTIVES: With ever increasing mandates to reduce costs and increase the
      quality of pain management, health care institutions are faced with the challenge
      of adopting innovative technologies and shifting workflows to provide value-based
      care. Transaction cost economic analysis can provide comparative evaluation of
      the consequences of these changes in the delivery of care. The aim of this study
      was to establish proof-of-concept using transaction cost analysis to examine
      chronic pain management in-clinic and through telehealth. METHODS: Participating
      health care providers were asked to identify and describe two comparable
      completed transactions for patients with chronic pain: one consultation between
      patient and specialist in-clinic and the other a telehealth presentation of a
      patient's case by the primary care provider to a team of pain medicine
      specialists. Each provider completed two on-site interviews. Focus was on the
      time, value of time, and labor costs per transaction. Number of steps, time, and
      costs for providers and patients were identified. RESULTS: Forty-six discrete
      steps were taken for the in-clinic transaction, and 27 steps were taken for the
      telehealth transaction. Although similar in costs per patient ($332.89 in-clinic
      vs. $376.48 telehealth), the costs accrued over 153 business days in-clinic and 4
      business days for telehealth. Time elapsed between referral and completion of
      initial consultation was 72 days in-clinic, 4 days for telehealth. CONCLUSIONS:
      U.S. health care is moving toward the use of more technologies and practices, and
      the information provided by transaction cost analyses of care delivery for pain
      management will be important to determine actual cost savings and benefits.

PMID- 25616058
TI  - Rod electrical coupling is controlled by a circadian clock and dopamine in mouse
      retina.
AB  - Rod single-photon responses are critical for vision in dim light. Electrical
      coupling via gap junction channels shapes the light response properties of
      vertebrate photoreceptors, but the regulation of rod coupling and its impact on
      the single-photon response have remained unclear. To directly address these
      questions, we developed a perforated patch-clamp recording technique and recorded
      from single rod inner segments in isolated intact neural mouse retinae,
      maintained by superfusion. Experiments were conducted at different times of the
      day or under constant environmental conditions, at different times across the
      circadian cycle. We show that rod electrical coupling is regulated by a circadian
      clock and dopamine, so that coupling is weak during the day and strong at night.
      Altogether, patch-clamp recordings of single-photon responses in mouse rods,
      tracer coupling, receptive field measurements and pharmacological manipulations
      of gap junction and dopamine receptor activity provide compelling evidence that
      rod coupling is modulated in a circadian manner. These data are consistent with
      computer modelling. At night, single-photon responses are smaller due to
      coupling, but the signal-to-noise ratio for a dim (multiphoton) light response is
      increased at night because of signal averaging between coupled rods.

PMID- 25616059
TI  - Emotional disorders in pairs of patients and their family members during and
      after ICU stay.
AB  - INTRODUCTION: Patients and family members undergo different experiences of
      suffering from emotional disorders during ICU stay and after ICU discharge. The
      purpose of this study was to compare the incidence of anxiety, depression and
      post-traumatic stress disorder (PTSD) symptoms in pairs (patient and respective
      family member), during stay at an open visit ICU and at 30 and 90-days post-ICU
      discharge. We hypothesized that there was a positive correlation with the
      severity of symptoms among pairs and different patterns of suffering over time.
      METHODS: A prospective study was conducted in a 22-bed adult general ICU
      including patients with >48 hours stay. The Hospital Anxiety and Depression Scale
      (HADS) was completed by the pairs (patients/respective family member). Interviews
      were made by phone at 30 and 90-days post-ICU discharge using the Impact of Event
      Scale (IES) and the HADS. Multivariate models were constructed to predict IES
      score at 30 days for patients and family members. RESULTS: Four hundred and
      seventy one family members and 289 patients were interviewed in the ICU forming
      184 pairs for analysis. Regarding HADS score, patients presented less symptoms
      than family members of patients who survived and who deceased at 30 and 90-days
      (p<0.001). However, family members of patients who deceased scored higher anxiety
      and depression symptoms (p = 0.048) at 90-days when compared with family members
      of patients who survived. Patients and family members at 30-days had a similar
      IES score, but it was higher in family members at 90-days (p = 0.019). For both
      family members and patients, age and symptoms of anxiety and depression during
      ICU were the major determinants for PTSD at 30-days. CONCLUSIONS: Anxiety,
      depression and PTSD symptoms were higher in family members than in the patients.
      Furthermore, these symptoms in family members persisted at 3 months, while they
      decreased in patients.

PMID- 25616061
TI  - A ghrelin receptor agonist is an effective colokinetic in rats with diet-induced
      constipation.
AB  - BACKGROUND: Despite constipation being a common problem, the treatments that are
      available have side effects and are only partly effective. Recent studies show
      that centrally penetrant ghrelin receptor agonists cause defecation in humans and
      other species. Here, we describe some features of a rat model of low fiber
      induced constipation, and investigate the effectiveness of the ghrelin agonist,
      capromorelin. METHODS: Rats were given low-fiber diets for 5 weeks. Their
      colorectal responsiveness to distension and to a behavioral test, water avoidance
      and colon histology were compared to those of rats on a standard diet. KEY
      RESULTS: After the low-fiber diet, distension of the colon produced fewer
      propulsive contractions, behaviorally induced defecation was reduced, and the
      lining of the colorectum was inflamed. However, capromorelin was similarly
      effective in causing defecation in constipated and non-constipated rats.
      CONCLUSIONS & INFERENCES: Low-fiber diet in rats produces a constipation
      phenotype, characterized by reduced responsiveness of the colorectum to
      distension and to a behavioral stimulus of defecation, water avoidance. The
      effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor
      stimulants may be effective in treating constipation.

PMID- 25616060
TI  - The NF-kappaB regulator Bcl-3 modulates inflammation during contact
      hypersensitivity reactions in radioresistant cells.
AB  - Bcl-3 is an atypical member of the IkappaB family. Bcl-3 functions as a cofactor
      of p50/NF-kappaB1 or p52/NF-kappaB2 homodimers in nuclei, where it modulates NF
      kappaB-regulated transcription in a context-dependent way. Bcl-3 has tumorigenic
      potential, is critical in host defense of pathogens, and has been reported to
      ameliorate or exacerbate inflammation, depending on disease model. However, cell
      specific functions of Bcl-3 remain largely unknown. Here, we explored the role of
      Bcl-3 in a contact hypersensitivity (CHS) mouse model, which depends on the
      interplay between keratinocytes and immune cells. Bcl-3-deficient mice exhibited
      an exacerbated and prolonged CHS response to oxazolone. Increased inflammation
      correlated with higher production of chemokines CXCL2, CXCL9, and CXCL10, and
      consequently increased recruitment of neutrophils and CD8(+) T cells. BM chimera
      experiments indicated that the ability of Bcl-3 to reduce the CHS response
      depended on Bcl-3 activity in radioresistant cells. Specific ablation of Bcl-3 in
      keratinocytes resulted in increased production of CXCL9 and CXCL10 and sustained
      recruitment of specifically CD8(+) T cells. These findings identify Bcl-3 as a
      critical player during the later stage of the CHS reaction to limit inflammation
      via actions in radioresistant cells, including keratinocytes. 

PMID- 25616062
TI  - Why the definition of high risk has been inappropriately used in previous carotid
      trials.
AB  - Carotid artery revascularization by endarterectomy is an effective means of
      stroke prevention in selected patients with carotid stenosis. With the
      development of endovascular techniques, carotid artery stenting (CAS) has been
      proposed as a viable alternative to carotid endarterectomy (CEA), particularly in
      patients considered at high risk for CEA. Guidelines have established criteria
      that outline these patients who are considered at "high risk" for complications
      after CEA, to whom CAS may provide benefit. The validity of these theoretical
      high-risk criteria, however, is yet unproven, and, as a consequence, there is no
      clear evidence suggesting that the risk with CAS is lower in these high-risk
      patients compared with CEA. This manuscript summarizes the role of "high risk"
      within recent trials and discusses why the optimal treatment for these patients
      with deemed high risk for surgery remains a matter of debate.

PMID- 25616063
TI  - Is the increased presence of CD8 T-lymphocytes related to serotonin levels in
      Chagas disease?

PMID- 25616064
TI  - Hand therapy services for rural and remote residents: Results of a survey of
      Australian occupational therapists and physiotherapists.
AB  - OBJECTIVE: The aim of this study was to explore how interventions were provided
      to meet the needs of rural/remote residents who have had a traumatic hand injury,
      including the coordination of services between rural/remote and metro/regional
      therapists. Barriers to providing services, use of technology and professional
      support provided to therapists in rural/remote areas were also explored. DESIGN:
      Cross-sectional survey. SETTING: Metropolitan/regional and rural/remote public
      health facilities in Australia. PARTICIPANTS: Occupational therapists and
      physiotherapists who provide hand therapy to rural/remote patients. MAIN OUTCOME
      MEASURE: Quantitative and qualitative questionnaire responses analysed with
      descriptive statistics and inductive analysis. RESULTS: There were 64 respondents
      out of a possible 185. Over half of rural/remote respondents provided initial
      splinting and exercise prescriptions, and over 85% reported that they continued
      with exercise protocols. Videoconferencing technology for patient intervention
      and clinical review was used by 39.1% respondents. Barriers to providing services
      in rural/remote locations included transport, travelling time, limited staff, and
      lack of expert knowledge in hand injuries or rural/remote health care. Four major
      themes emerged from the open-ended questions: working relationships, patient
      centred care, staff development and education, and rural and remote practice.
      CONCLUSION: The use of technology across Australia to support rural/remote
      patient intervention requires attention to achieve equity and ease of use.
      Flexible and realistic goals and interventions should be considered when working
      with rural/remote patients. A shared care approach between metropolitan/regional
      and rural/remote therapists can improve understanding of rural/remote issues and
      provide support to therapists. Further research is recommended to determine the
      suitability of this approach when providing hand therapy to rural/remote
      residents.

PMID- 25616066
TI  - Transcription initiation determines its end.
AB  - A new study published in this issue of Molecular Cell (Oktaba et al., 2015)
      suggests widespread involvement of promoters in the regulation of alternative
      cleavage and polyadenylation of mRNAs in Drosophila neurons. 

PMID- 25616065
TI  - ZMP: a master regulator of one-carbon metabolism.
AB  - In this issue, Kim et al. (2015) show that ZMP (5-aminoimidazole-4-carboxamide
      ribonucleotide) binds to and activates a conserved riboswitch to regulate
      expression of one-carbon metabolism genes. 

PMID- 25616069
TI  - Bidentate NHC^pyrozolate ligands in luminescent platinum(II) complexes.
AB  - A bidentate C^N donor set derived from an N-heterocyclic carbene (NHC) precursor
      linked to a trifluoromethyl (CF3) functionalized pyrazole ring is described for
      the first time. The ligands have been employed to prepare four new phosphorescent
      complexes by the coordination of platinum(II) centres bearing cyclometalated
      phenyl-pyridine/triazole-pyridine chelates. The electronic and steric
      environments of these complexes were tuned through the incorporation of suitable
      substituents in the phenyl-pyridine/triazole-pyridine ligands, wherein the
      position of the phenyl-ring substituent (a CF3 group) also directs the selective
      adoption of either a trans or a cis configuration between the C(NHC) and the
      C(phenyl) donor atoms. Molecular structures obtained by X-ray diffraction for
      three of the complexes confirm a distorted square-planar configuration around the
      platinum centre, and DFT calculations show that the substituents have a
      significant influence on the energies of the frontier orbitals. Moreover, a
      platinum(II) complex featuring the new bidentate NHC^pyrazolate ligand and a
      bulky adamantyl functionalized pyridine-triazole luminophore was observed to be
      highly emissive and exhibiting a sky-blue luminescence (lambda(Em) = 470 nm) with
      photoluminescence quantum yields as high as 50% in doped PMMA matrices. A
      complete photophysical investigation of all of the complexes in solution as well
      as in the solid state is herein reported.

PMID- 25616067
TI  - An ancient riboswitch class in bacteria regulates purine biosynthesis and one
      carbon metabolism.
AB  - Over 30 years ago, ZTP (5-aminoimidazole-4-carboxamide riboside 5'-triphosphate),
      a modified purine biosynthetic intermediate, was proposed to signal 10-formyl
      tetrahydrofolate (10f-THF) deficiency in bacteria. However, the mechanisms by
      which this putative alarmone or its precursor ZMP (5-aminoimidazole-4-carboxamide
      ribonucleotide, also known as AICAR) brings about any metabolic changes remain
      unexplained. Herein, we report the existence of a widespread riboswitch class
      that is most commonly associated with genes related to de novo purine
      biosynthesis and one-carbon metabolism. Biochemical data confirm that members of
      this riboswitch class selectively bind ZMP and ZTP with nanomolar affinity while
      strongly rejecting numerous natural analogs. Indeed, increases in the ZMP/ZTP
      pool, caused by folate stress in bacterial cells, trigger changes in the
      expression of a reporter gene fused to representative ZTP riboswitches in vivo.
      The wide distribution of this riboswitch class suggests that ZMP/ZTP signaling is
      important for species in numerous bacterial lineages.

PMID- 25616070
TI  - Infrared photoisomerization of 1-propanol CD3 and OD trapped in four cryogenic
      matrices: Ne, N2, Ar, and Xe.
AB  - The conformational equilibria and isomerization processes of 1-propanol -OD and 
      CD3 have been studied by vibrational spectroscopy at low temperatures in four
      cryogenic matrices to investigate the effect of deuteration on their
      photochemistry. These isotopic species were selectively irradiated in the nuOH
      and nuOD domains, resulting in the identification of several conformers that are
      able to interconvert upon selective IR irradiation. The experimental results were
      compared with theoretical geometries obtained at the B3LYP/6-311+G(d) level of
      theory. Alkyl chain isomerization can be induced in rare gas and nitrogen
      cryogenic matrices by suitable selective irradiation. Selective excitation of the
      OH and OD stretches of two Gauche isomers transfers the alkyl chain from the
      gauche to the trans form. The competition between intramolecular vibrational
      energy relaxation and the matrix-dopant interaction determines the torsional
      subspace dynamics of the vibrationally excited propanol molecules. 

PMID- 25616068
TI  - A combined proteomics/genomics approach links hepatitis C virus infection with
      nonsense-mediated mRNA decay.
AB  - Hepatitis C virus (HCV) is a leading cause of liver disease, but insight into
      virus-host interactions remains limited. We systematically used affinity
      purification/mass spectrometry to define the host interactions of all ten HCV
      proteins in hepatoma cells. We combined these studies with RNAi knockdown of
      corresponding genes using a two-step scoring approach to generate a map of 139
      high-confidence HCV-host protein-protein interactions. We found mitochondrial
      proteins highly involved in HCV infection and characterized an interaction
      between the viral core protein and host protein within bgcn homolog (WIBG).
      Expression of core prevents WIBG from binding its regular interaction partners
      Y14 and Magoh, two known mediators of the nonsense-mediated mRNA decay pathway.
      We discovered that this surveillance pathway is disrupted in HCV-infected cells,
      causing potentially harmful transcripts to accumulate. Our study provides a
      comprehensive view of HCV-host interactions and uncovers mechanisms for how HCV
      perturbs host functions during infection. 

PMID- 25616071
TI  - Life-threating upper gastrointestinal bleeding due to a primary aorto-jejunal
      fistula.
AB  - INTRODUCTION: Primary aorto-enteric fistula (AEF) is an uncommon life-threating
      condition. Only 4% of them involve the jejunum or ileum and its mortality ranges
      from 33 to 85%. PRESENTATION OF CASE: A 54-year-old female was admitted to the
      Emergency Department with syncope and hematemesis. The esophagogastroduodenoscopy
      found a pulsatile vessel in the second portion of the duodenum. A computed
      tomography scan showed an AEF with an infrarenal aortic aneurysm and iliac artery
      thrombosis. During surgery, an infrarenal aortic aneurysm complicated with an
      aorto-jejunal fistula was found. An axilo-bifemoral bypass, open repair of the
      aneurysm and segmental small bowel resection with primary suture of the jejunal
      defect were performed. DISCUSSION: Depending on previous aortic grafting, AEF can
      be classified as primary or secondary. Primary AEF is usually caused by an
      untreated abdominal aortic aneurysm, commonly presenting an infectious etiology.
      The main clinical sign is a "herald" hemorrhage. The EGD is considered as the
      first step in diagnosing AEF. The treatment of choice for AEF is emergent
      surgery. Use of broad-spectrum antibiotics is mandatory in the postoperative
      period to avoid fistula recurrence. CONCLUSION: AEF is a rare entity with a high
      mortality. High clinical suspicion is essential to make a correct diagnosis,
      which is crucial for the prognosis of these patients, such is the case of our
      patient. If hemodynamic stability is achieved, it allows to employ surgical
      strategies in which extra-abdominal bypass is performed before fistula is
      treated.

PMID- 25616072
TI  - Comparison of cognitive deficits among drug-naive patients with schizophrenia and
      major depressive disorder.
AB  - BACKGROUND: Cognitive deficits have been well-established among patients with
      severe mental illness. The aim of this study was to clarify the patterns of
      cognitive deficits in drug-naive patients with schizophrenia and non-psychotic
      major depressive disorder (MDD) as compared with controls. METHODS: Thirty drug
      naive participants with schizophrenia, 30 counterparts with non-psychotic MDD,
      and 30 age-, sex-, and education years-matched healthy controls were recruited.
      Neuropsychological tests, including the Wisconsin Card Test (WCST), the
      Continuous Performance Test (CPT) and the Finger Tapping Test (FTT), were
      administered. RESULTS: Patients with schizophrenia performed more poorly than the
      patients with MDD and the normal controls in the WCST. The patients with
      schizophrenia and the patients with MDD both performed more poorly than the
      normal controls in the CPT. The patients with MDD also performed more poorly than
      the normal controls in the FTT. LIMITATIONS: The age of onset of MDD in this
      study was younger than in previous reports. The cross-sectional design, small
      sample sizes, and limited numbers of neuropsychological domains in this study are
      all obstacles to making a clear causal conclusion. CONCLUSIONS: These results
      revealed a distinct pattern of neurocognitive dysfunction among drug-naive
      patients with schizophrenia and MDD, which may imply different underlying
      neurobiological mechanisms in schizophrenia and MDD.

PMID- 25616073
TI  - A 259.6 MUW HRV-EEG Processor With Nonlinear Chaotic Analysis During Mental
      Tasks.
AB  - A system-on-chip (SoC) with nonlinear chaotic analysis (NCA) is presented for
      mental task monitoring. The proposed processor treats both heart rate variability
      (HRV) and electroencephalography (EEG). An independent component analysis (ICA)
      accelerator decreases the error of HRV extraction from 5.94% to 1.84% in the
      preprocessing step. Largest Lyapunov exponents (LLE), as well as linear features
      such as mean and standard variation and sub-band power, are calculated with NCA
      acceleration. Measurements with mental task protocols result in confidence level
      of 95%. Thanks to the hardware acceleration, the chaos-processor fabricated in
      0.13 MUm CMOS technology consumes only 259.6 MUW. 

PMID- 25616074
TI  - Optimal Design of Wireless Power Transmission Links for Millimeter-Sized
      Biomedical Implants.
AB  - This paper presents a design methodology for RF power transmission to millimeter
      sized implantable biomedical devices. The optimal operating frequency and coil
      geometries are found such that power transfer efficiency (PTE) and tissue-loss
      constrained allowed power are maximized. We define receiver power reception
      susceptibility (Rx-PRS) and transmitter figure of merit (Tx-FoM) such that their
      multiplication yields the PTE. Rx-PRS and Tx-FoM define the roles of the Rx and
      Tx in the PTE, respectively. First, the optimal Rx coil geometry and operating
      frequency range are identified such that the Rx-PRS is maximized for given
      implant constraints. Since the Rx is very small and has lesser design freedom
      than the Tx, the overall operating frequency is restricted mainly by the Rx. Rx
      PRS identifies such operating frequency constraint imposed by the Rx. Secondly,
      the Tx coil geometry is selected such that the Tx-FoM is maximized under the
      frequency constraint at which the Rx-PRS was saturated. This aligns the target
      frequency range of Tx optimization with the frequency range at which Rx
      performance is high, resulting in the maximum PTE. Finally, we have found that
      even in the frequency range at which the PTE is relatively flat, the tissue loss
      per unit delivered power can be significantly different for each frequency. The
      Rx-PRS can predict the frequency range at which the tissue loss per unit
      delivered power is minimized while PTE is maintained high. In this way, frequency
      adjustment for the PTE and tissue-loss-constrained allowed power is realized by
      characterizing the Rx-PRS. The design procedure was verified through full-wave
      electromagnetic field simulations and measurements using de-embedding method. A
      prototype implant, 1 mm in diameter, achieved PTE of 0.56% ( -22.5 dB) and power
      delivered to load (PDL) was 224 MUW at 200 MHz with 12 mm Tx-to-Rx separation in
      the tissue environment. 

PMID- 25616075
TI  - An 11 MUW Sub-pJ/bit Reconfigurable Transceiver for mm-Sized Wireless Implants.
AB  - A wirelessly powered 11 MUW transceiver for implantable devices has been designed
      and demonstrated through 35 mm of porcine heart tissue. The prototype was
      implemented in 65 nm CMOS occupying 1 mm * 1 mm with a 2 mm * 2 mm off-chip
      antenna. The IC consists of a rectifier, regulator, demodulator, modulator,
      controller, and sensor interface. The forward link transfers power and data on a
      1.32 GHz carrier using low-depth ASK modulation that minimizes impact on power
      delivery and achieves from 4 to 20 Mbps with 0.3 pJ/bit at 4 Mbps. The
      backscattering link modulates the antenna impedance with a configurable load for
      operation in diverse biological environments and achieves up to 2 Mbps at 0.7
      pJ/bit. The device supports TDMA, allowing for operation of multiple devices from
      a single external transceiver. 

PMID- 25616076
TI  - An On-Chip Multi-Voltage Power Converter With Leakage Current Prevention Using
      0.18 MUm High-Voltage CMOS Process.
AB  - In this paper, we present an on-chip multi-voltage power converter incorporating
      of a quad-voltage timing-control rectifier and regulators to produce +/-12 V and
      +/-1.8 V simultaneously through inductive powering. The power converter achieves
      a PCE of 77.3% with the delivery of more than 100 mW to the implant. The proposed
      rectifier adopts a two-phase start-up scheme and mixed-voltage gate controller to
      avoid substrate leakage current. This current cannot be prevented by the
      conventional dynamic substrate biasing technique when using the high-voltage CMOS
      process with transistor threshold voltage higher than the turn-on voltage of
      parasitic diodes. High power conversion efficiency is achieved by 1) substrate
      leakage current prevention, 2) operating all rectifying transistors as switches
      with boosted gate control voltages, and 3) compensating the delayed turn-on and
      preventing reverse leakage current of rectifying switches with the proposed look
      ahead comparator. This chip occupies an area of 970 MUm * 4500 MUm in a 0.18 MU m
      32 V HV CMOS process. The quad-voltage timing-control rectifier alone is able to
      output a high DC voltage at the range of [2.5 V, 25 V]. With this power
      converter, both bench-top experiment and in-vivo power link test using a rat
      model were validated. 

PMID- 25616077
TI  - Composites of Eu(3+)-doped calcium apatite nanoparticles and silica particles:
      comparative study of two preparation methods.
AB  - We synthesized composites of Eu(3+)-doped calcium apatite (CaAp:Eu(3+))
      nanoparticles and silica particles via two methods: (i) in situ synthesis of
      CaAp:Eu(3+) in the presence of silica particles and (ii) electrostatic adsorption
      of CaAp:Eu(3+) nanoparticles on silica particle surfaces. In both methods,
      submicrometer spherical silica particles were covered with CaAp:Eu(3+)
      nanoparticles without forming any impurity phases, as confirmed by X-ray
      diffractometry, Fourier-transform infrared spectroscopy, and scanning electron
      microscopy. In method i, part of the silica surface acted as a nucleation site
      for apatite crystals and silica particles were inhomogeneously covered with
      CaAp:Eu(3+) nanoparticles. In method ii, positively charged CaAp:Eu(3+)
      nanoparticles were homogeneously adsorbed on the negatively charged silica
      surface through electrostatic interactions. The bonds between the silica surface
      and CaAp:Eu(3+) nanoparticles are strong enough not to break under ultrasonic
      irradiation, irrespective of the synthetic method used. The composite particles
      showed red photoluminescence corresponding to 4f -> 4f transitions of Eu(3+)
      under near-UV irradiation. Although the absorption coefficient of the forbidden
      4f -> 4f transitions of Eu(3+) was small, the red emission was detectable with a
      commercial fluorescence microscope because the CaAp:Eu(3+) nanoparticles
      accumulated on the silica particle surfaces. 

PMID- 25616079
TI  - Adult respiratory outcomes of extreme preterm birth. A regional cohort study.
AB  - RATIONALE: Lifetime respiratory function after extremely preterm birth
      (gestational age<=28 wk or birth weight<=1,000 g) is unknown. OBJECTIVES: To
      compare changes from 18-25 years of age in respiratory health, lung function, and
      airway responsiveness in young adults born extremely prematurely to that of term
      born control subjects. METHODS: Comprehensive lung function investigations and
      interviews were conducted in a population-based sample of 25-year-old subjects
      born extremely prematurely in western Norway in 1982-1985, and in matched term
      born control subjects. Comparison was made to similar data collected at 18 years
      of age. MEASUREMENTS AND MAIN RESULTS: At 25 years of age, 46/51 (90%) eligible
      subjects born extremely prematurely and 39/46 (85%) control subjects
      participated. z-Scores for FEV1, forced expiratory flow at 25-75% of vital
      capacity, and FEV1/FVC were significantly reduced in subjects born extremely
      prematurely by 1.02, 1.26, and 0.88, respectively, and airway resistance
      (kPa/L/s) was increased (0.23 versus 0.18). Residual volume to total lung
      capacity increased with severity of neonatal bronchopulmonary dysplasia.
      Responsiveness to methacholine (dose-response slope; 3.16 versus 0.85) and
      bronchial lability index (7.5 versus 4.8%) were increased in subjects born
      extremely prematurely. Lung function changes from 18 to 25 years and respiratory
      symptoms were similar in the prematurely born and term-born groups. CONCLUSIONS:
      Lung function in early adult life was in the normal range in the majority of
      subjects born extremely prematurely, but methacholine responsiveness was more
      pronounced than in term-born young adults, suggesting a need for ongoing
      pulmonary monitoring in this population.

PMID- 25616078
TI  - Enzymatic cleavage of uracil-containing single-stranded DNA linkers for the
      efficient release of affinity-selected circulating tumor cells.
AB  - We report a novel strategy to enzymatically release affinity-selected cells, such
      as circulating tumor cells (CTCs), from surfaces with high efficiency (~90%)
      while maintaining cell viability (>85%). The strategy utilizes single-stranded
      DNAs that link a capture antibody to the surfaces of a CTC selection device. The
      DNA linkers contain a uracil residue that can be cleaved. 

PMID- 25616080
TI  - Learning to rank for blind image quality assessment.
AB  - Blind image quality assessment (BIQA) aims to predict perceptual image quality
      scores without access to reference images. State-of-the-art BIQA methods
      typically require subjects to score a large number of images to train a robust
      model. However, subjective quality scores are imprecise, biased, and
      inconsistent, and it is challenging to obtain a large-scale database, or to
      extend existing databases, because of the inconvenience of collecting images,
      training the subjects, conducting subjective experiments, and realigning human
      quality evaluations. To combat these limitations, this paper explores and
      exploits preference image pairs (PIPs) such as the quality of image Ia is better
      than that of image Ib for training a robust BIQA model. The preference label,
      representing the relative quality of two images, is generally precise and
      consistent, and is not sensitive to image content, distortion type, or subject
      identity; such PIPs can be generated at a very low cost. The proposed BIQA method
      is one of learning to rank. We first formulate the problem of learning the
      mapping from the image features to the preference label as one of classification.
      In particular, we investigate the utilization of a multiple kernel learning
      algorithm based on group lasso to provide a solution. A simple but effective
      strategy to estimate perceptual image quality scores is then presented.
      Experiments show that the proposed BIQA method is highly effective and achieves a
      performance comparable with that of state-of-the-art BIQA algorithms. Moreover,
      the proposed method can be easily extended to new distortion categories. 

PMID- 25616081
TI  - Automatic face naming by learning discriminative affinity matrices from weakly
      labeled images.
AB  - Given a collection of images, where each image contains several faces and is
      associated with a few names in the corresponding caption, the goal of face naming
      is to infer the correct name for each face. In this paper, we propose two new
      methods to effectively solve this problem by learning two discriminative affinity
      matrices from these weakly labeled images. We first propose a new method called
      regularized low-rank representation by effectively utilizing weakly supervised
      information to learn a low-rank reconstruction coefficient matrix while exploring
      multiple subspace structures of the data. Specifically, by introducing a
      specially designed regularizer to the low-rank representation method, we penalize
      the corresponding reconstruction coefficients related to the situations where a
      face is reconstructed by using face images from other subjects or by using
      itself. With the inferred reconstruction coefficient matrix, a discriminative
      affinity matrix can be obtained. Moreover, we also develop a new distance metric
      learning method called ambiguously supervised structural metric learning by using
      weakly supervised information to seek a discriminative distance metric. Hence,
      another discriminative affinity matrix can be obtained using the similarity
      matrix (i.e., the kernel matrix) based on the Mahalanobis distances of the data.
      Observing that these two affinity matrices contain complementary information, we
      further combine them to obtain a fused affinity matrix, based on which we develop
      a new iterative scheme to infer the name of each face. Comprehensive experiments
      demonstrate the effectiveness of our approach. 

PMID- 25616082
TI  - Dependent online kernel learning with constant number of random Fourier features.
AB  - Traditional online kernel learning analysis assumes independently identically
      distributed (i.i.d.) about the training sequence. Recent studies reveal that when
      the loss function is smooth and strongly convex, given T i.i.d. training
      instances, a constant sampling complexity of random Fourier features is
      sufficient to ensure O(logT/T) convergence rate of excess risk, which is optimal
      in online kernel learning up to a logT factor. However, the i.i.d. hypothesis is
      too strong in practice, which greatly impairs their value. In this paper, we
      study the sampling complexity of random Fourier features in online kernel
      learning under non-i.i.d. assumptions. We prove that the sampling complexity
      under non-i.i.d. settings is also constant, but the convergence rate of excess
      risk is O(logT/T+ phi) , where phi is the mixing coefficient measuring the extent
      of non-i.i.d. of training sequence. We conduct experiments both on artificial and
      real large-scale data sets to verify our theories. 

PMID- 25616083
TI  - Mode-Dependent Stochastic Synchronization for Markovian Coupled Neural Networks
      With Time-Varying Mode-Delays.
AB  - This paper investigates the stochastic synchronization problem for Markovian
      hybrid coupled neural networks with interval time-varying mode-delays and random
      coupling strengths. The coupling strengths are mutually independent random
      variables and the coupling configuration matrices are nonsymmetric. A mode
      dependent augmented Lyapunov-Krasovskii functional (LKF) is proposed, where some
      terms involving triple or quadruple integrals are considered, which makes the LKF
      matrices mode-dependent as much as possible. This gives significant improvement
      in the synchronization criteria, i.e., less conservative results can be obtained.
      In addition, by applying an extended Jensen's integral inequality and the
      properties of random variables, new delay-dependent synchronization criteria are
      derived. The obtained criteria depend not only on upper and lower bounds of mode
      delays but also on mathematical expectations and variances of the random coupling
      strengths. Finally, two numerical examples are provided to demonstrate the
      feasibility of the proposed results. 

PMID- 25616084
TI  - Integrated cross-coupling strategy for an alpha-carboline-based Aurora B kinase
      inhibitor.
AB  - An efficient and practical synthetic process for an alpha-carboline-based Aurora
      B kinase inhibitor was achieved using an integrated Pd-catalyzed cross-coupling
      strategy. The process features a mild and efficient method for construction of
      the alpha-carboline core by employing a Pd-catalyzed sequence of Buchwald-Hartwig
      amination and intramolecular direct C-H arylation at the ortho position of an
      unsubstituted aniline moiety, which is a key functionality for further
      derivatization with a Suzuki coupling via Sandmeyer iodination. The process has
      eliminated expensive starting materials and column chromatography purifications
      and enabled considerable enhancement of the total yield from 11% to 48%. 

PMID- 25616085
TI  - Virtual MEG Helmet: Computer Simulation of an Approach to Neuromagnetic Field
      Sampling.
AB  - Head movements during an MEG recording are commonly considered an obstacle. In
      this computer simulation study, we introduce an approach, the virtual MEG helmet
      (VMH), which employs the head movements for data quality improvement. With a VMH,
      a denser MEG helmet is constructed by adding new sensors corresponding to
      different head positions. Based on the Shannon's theory of communication, we
      calculated the total information as a figure of merit for comparing the actual
      306-sensor Elekta Neuromag helmet to several types of the VMH. As source models,
      we used simulated randomly distributed source current (RDSC), simulated auditory
      and somatosensory evoked fields. Using the RDSC model with the simulation of 360
      recorded events, the total information (bits/sample) was 989 for the most
      informative single head position and up to 1272 for the VMH (addition of 28.6%).
      Using simulated AEFs, the additional contribution of a VMH was 12.6% and using
      simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can
      provide a more informative sampling of the neuromagnetic field during the same
      recording time than measuring the MEG from one head position. VMH can, in some
      situations, improve source localization of the neuromagnetic fields related to
      the normal and pathological brain activity. This should be investigated further
      employing real MEG recordings. 

PMID- 25616086
TI  - Extracting Various Classes of Data From Biological Text Using the Concept of
      Existence Dependency.
AB  - One of the key goals of biological natural language processing (NLP) is the
      automatic information extraction from biomedical publications. Most current
      constituency and dependency parsers overlook the semantic relationships between
      the constituents comprising a sentence and may not be well suited for capturing
      complex long-distance dependences. We propose in this paper a hybrid constituency
      dependency parser for biological NLP information extraction called EDCC. EDCC
      aims at enhancing the state of the art of biological text mining by applying
      novel linguistic computational techniques that overcome the limitations of
      current constituency and dependency parsers outlined earlier, as follows: 1) it
      determines the semantic relationship between each pair of constituents in a
      sentence using novel semantic rules; and 2) it applies a semantic relationship
      extraction model that extracts information from different structural forms of
      constituents in sentences. EDCC can be used to extract different types of data
      from biological texts for purposes such as protein function prediction, genetic
      network construction, and protein-protein interaction detection. We evaluated the
      quality of EDCC by comparing it experimentally with six systems. Results showed
      marked improvement. 

PMID- 25616087
TI  - Feasibility of omitting cortical renorrhaphy during robot-assisted partial
      nephrectomy: a matched analysis.
AB  - BACKGROUND AND PURPOSE: To assess the safety of omitting cortical renorrhaphy
      during robot-assisted partial nephrectomy and measure preliminary functional
      outcomes. PATIENTS AND METHODS: Fifteen robot-assisted partial nephrectomies were
      performed with a running, base-layer suture for the collecting system and vessel
      hemostasis but without cortical renorrhaphy. The nonrenorrhaphy group was matched
      1:2 by R.E.N.A.L. nephrometry score to a running, sliding-clip cortical
      renorrhaphy group retrospectively. Intraoperative blood loss, urine leaks,
      postoperative bleeds, and functional outcomes were evaluated. Predictors of
      %volume loss were evaluated using multivariable regression. RESULTS: No
      differences were seen between renorrhaphy and nonrenorrhaphy in sex (P=0.53), age
      (P=0.14), body mass index (P=0.08), Charlson score (P=0.44), tumor diameter
      (P=0.55), nephrometry score (P=0.77), preoperative glomerular filtration rate
      (GFR, P=0.63), or the amount of resected healthy kidney margin (P=0.21). Warm
      ischemia time was less for the nonrenorrhaphy group (P<0.002). One pseudoaneurysm
      necessitating embolization (1/30=3%) was seen in the renorrhaphy group compared
      with none in the nonrenorrhaphy group. No urine leaks occurred in either group.
      The median %GFR loss was 8.8% for renorrhaphy and 4.4% for nonrenorrhaphy
      (P=0.14) at a median follow-up of 4.1 months. The median %volume loss was 17
      cm(3) for renorrhaphy and 9 cm(3) for nonrenorrhaphy (P=0.003). In a
      multivariable model, both cortical renorrhaphy (P=0.004) and tumor diameter
      (P=0.004) were predictors of %volume loss. CONCLUSION: Omission of cortical
      renorrhaphy appears feasible with no urine leaks or bleeding complications
      observed. The percent renal volume loss was improved by omission of cortical
      renorrhaphy. Reconstruction technique is important to control for when studying
      renal function after partial nephrectomy.

PMID- 25616089
TI  - Image Pair Analysis With Matrix-Value Operator.
AB  - Image pair analysis provides significant image pair priori which describes the
      dependency between training image pairs for various learning-based image
      processing. For avoiding the information loss caused by vectorizing training
      images, a novel matrix-value operator learning method is proposed for image pair
      analysis. Sample-dependent operators, named image pair operators (IPOs) by us,
      are employed to represent the local image-to-image dependency defined by each of
      the training image pairs. A linear combination of IPOs is learned via operator
      regression for representing the global dependency between input and output images
      defined by all of the training image pairs. The proposed operator learning method
      enjoys the image-level information of training image pairs because IPOs enable
      training images to be used without vectorizing during the learning and testing
      process. By applying the proposed algorithm in learning-based super-resolution,
      the efficiency and the effectiveness of the proposed algorithm in learning image
      pair information is verified by experimental results. 

PMID- 25616088
TI  - The nutrient economy of Lodoicea maldivica, a monodominant palm producing the
      world's largest seed.
AB  - The iconic Lodoicea maldivica palm appears to invest heavily in reproduction,
      with females bearing the world's largest seeds and males producing copious
      pollen. We asked how these palms, which grow in extremely poor soils, obtain
      sufficient nutrients to support such high levels of reproductive function. Our
      study site was the Vallee de Mai UNESCO Site on Praslin, Seychelles. We measured
      the trees' allocations of dry matter, nitrogen (N) and phosphorus (P) to
      aboveground growth and reproduction, quantified stemflow and throughfall, and
      measured availabilities of N and P in the soil. We show that the nutrient costs
      of reproduction are very high in male and female plants, and for P far exceed
      those of vegetative growth. We describe how the palm leaves form a huge funnel
      that intercepts particulate material, especially pollen, which is flushed to the
      base of the trunk when it rains. In this way, Lodoicea improves its nutrient
      supply and that of its dispersal-limited offspring. Lodoicea shares many
      functional characteristics with dominant trees of other monodominant forests in
      the humid tropics. It also exhibits unique features, including its huge seed,
      effective funnelling mechanism and diverse community of closely associated
      animals, suggesting a long evolutionary history under relatively stable
      conditions. 

PMID- 25616090
TI  - Image Search Reranking With Hierarchical Topic Awareness.
AB  - With much attention from both academia and industrial communities, visual search
      reranking has recently been proposed to refine image search results obtained from
      text-based image search engines. Most of the traditional reranking methods cannot
      capture both relevance and diversity of the search results at the same time. Or
      they ignore the hierarchical topic structure of search result. Each topic is
      treated equally and independently. However, in real applications, images returned
      for certain queries are naturally in hierarchical organization, rather than
      simple parallel relation. In this paper, a new reranking method "topic-aware
      reranking (TARerank)" is proposed. TARerank describes the hierarchical topic
      structure of search results in one model, and seamlessly captures both relevance
      and diversity of the image search results simultaneously. Through a structured
      learning framework, relevance and diversity are modeled in TARerank by a set of
      carefully designed features, and then the model is learned from human-labeled
      training samples. The learned model is expected to predict reranking results with
      high relevance and diversity for testing queries. To verify the effectiveness of
      the proposed method, we collect an image search dataset and conduct comparison
      experiments on it. The experimental results demonstrate that the proposed
      TARerank outperforms the existing relevance-based and diversified reranking
      methods. 

PMID- 25616091
TI  - Topic Model for Graph Mining.
AB  - Graph mining has been a popular research area because of its numerous application
      scenarios. Many unstructured and structured data can be represented as graphs,
      such as, documents, chemical molecular structures, and images. However, an issue
      in relation to current research on graphs is that they cannot adequately discover
      the topics hidden in graph-structured data which can be beneficial for both the
      unsupervised learning and supervised learning of the graphs. Although topic
      models have proved to be very successful in discovering latent topics, the
      standard topic models cannot be directly applied to graph-structured data due to
      the "bag-of-word" assumption. In this paper, an innovative graph topic model
      (GTM) is proposed to address this issue, which uses Bernoulli distributions to
      model the edges between nodes in a graph. It can, therefore, make the edges in a
      graph contribute to latent topic discovery and further improve the accuracy of
      the supervised and unsupervised learning of graphs. The experimental results on
      two different types of graph datasets show that the proposed GTM outperforms the
      latent Dirichlet allocation on classification by using the unveiled topics of
      these two models to represent graphs. 

PMID- 25616092
TI  - Resilient Asynchronous Hinfinity Filtering for Markov Jump Neural Networks With
      Unideal Measurements and Multiplicative Noises.
AB  - This paper is concerned with the resilient Hinfinity filtering problem for a
      class of discrete-time Markov jump neural networks (NNs) with time-varying
      delays, unideal measurements, and multiplicative noises. The transitions of NNs
      modes and desired mode-dependent filters are considered to be asynchronous, and a
      nonhomogeneous mode transition matrix of filters is used to model the
      asynchronous jumps to different degrees that are also mode-dependent. The unknown
      time-varying delays are also supposed to be mode-dependent with lower and upper
      bounds known a priori. The unideal measurements model includes the phenomena of
      randomly occurring quantization and missing measurements in a unified form. The
      desired resilient filters are designed such that the filtering error system is
      stochastically stable with a guaranteed Hinfinity performance index. A
      monotonicity is disclosed in filtering performance index as the degree of
      asynchronous jumps changes. A numerical example is provided to demonstrate the
      potential and validity of the theoretical results. 

PMID- 25616093
TI  - New Decentralized Hinfinity Filter Design for Nonlinear Interconnected Systems
      Based on Takagi-Sugeno Fuzzy Models.
AB  - In this paper, the problem of Hinfinity filter design for nonlinear
      interconnected systems with time-varying delays through Takagi-Sugeno fuzzy
      models is revisited. Based on the fuzzy line-integral Lyapunov function approach
      and the reciprocally convex inequality, a delay-dependent decentralized Hinfinity
      filter is designed by guaranteeing the asymptotic stability and a prescribed
      Hinfinity performance index for the overall filter error system. A new sufficient
      condition for the existence of such a filter is established in terms of linear
      matrix inequalities. The present method provides improvements and produces better
      results than existing ones in the literature. Two examples are given to show the
      advantages and effectiveness of the proposed results. 

PMID- 25616094
TI  - Effect of a sigma-1 receptor agonist, cutamesine dihydrochloride (SA4503), on
      photoreceptor cell death against light-induced damage.
AB  - Cutamesine dihydrochloride is an agonist of sigma-1 receptor, which is a ligand
      operated receptor chaperone at the mitochondrion-associated endoplasmic reticulum
      (ER) membrane. ER stress plays a pivotal role in light irradiation-induced
      retinal damage. In the present study, we examined whether cutamesine is effective
      against experimental degenerative retinal damages in vitro and in vivo. The
      effects of cutamesine against white light-induced retinal photoreceptor damage
      were evaluated in vitro by measuring cell death. The expression of sigma-1
      receptor after the light exposure was examined by immunoblot analysis. The
      disruption of the mitochondrial membrane potential and caspase-3/7 activation
      after excessive light exposure were also examined. In addition, retinal damage in
      mice induced by irradiation to white light was evaluated using histological
      staining and electroretinography. Cutamesine reduced the cell death rate induced
      by light exposure, and the protective effect was prevented by N-[2-(3,4
      dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD-1047)
      dihydrobromide, a sigma-1 receptor antagonist. Sigma-1 receptor expression was
      decreased by light exposure, and cutamesine suppressed the decreased expression
      of sigma-1 receptor protein. Cutamesine also reduced the mitochondrial damage and
      reduced the elevated level of caspase 3/7 activity; this effect was attenuated by
      BD-1047. In in vivo studies, cutamesine suppressed the light-induced retinal
      dysfunction and thinning of the outer nuclear layer in the mouse retina. These
      findings indicate that cutamesine protects against retinal cell death in vitro
      and in vivo by the agonistic effect of sigma-1 receptor. Therefore, sigma-1
      receptor may have a potential as a therapeutic target in retinal diseases
      mediated by photoreceptor degeneration. 

PMID- 25616095
TI  - The regulation of gene expression in hair cells.
AB  - No genes have been discovered for which expression is limited only to inner ear
      hair cells. This is hardly surprising, since the number of mammalian genes is
      estimated to be 20-25,000, and each gene typically performs many tasks in various
      locations. Many genes are expressed in inner ear sensory cells and not in other
      cells of the labyrinth. However, these genes are also expressed in other
      locations, often in other sensory or neuronal cell types. How gene transcription
      is directed specifically to hair cells is unclear. Key transcription factors that
      act during development can specify cell phenotypes, and the hair cell is no
      exception. The transcription factor ATOH1 is well known for its ability to
      transform nonsensory cells of the developing inner ear into hair cells. And yet,
      ATOH1 also specifies different sensory cells at other locations, neuronal
      phenotypes in the brain, and epithelial cells in the gut. How it specifies hair
      cells in the inner ear, but alternate cell types in other locations, is not
      known. Studies of regulatory DNA and transcription factors are revealing
      mechanisms that direct gene expression to hair cells, and that determine the hair
      cell identity. The purpose of this review is to summarize what is known about
      such gene regulation in this key auditory and vestibular cell type.

PMID- 25616096
TI  - Targeted therapy in the treatment of uterine serous carcinoma.

PMID- 25616097
TI  - Economic evaluation of a pharmacogenetic dosing algorithm for coumarin
      anticoagulants in The Netherlands.
AB  - AIM: To investigate the cost-effectiveness of a pharmacogenetic dosing algorithm
      versus a clinical dosing algorithm for coumarin anticoagulants in The
      Netherlands. MATERIALS & METHODS: A decision-analytic Markov model was used to
      analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and
      acenocoumarol versus clinical dosing. RESULTS: Pharmacogenetic dosing increased
      costs by ?33 and quality-adjusted life-years (QALYs) by 0.001. The incremental
      cost-effectiveness ratios were ?28,349 and ?24,427 per QALY gained for
      phenprocoumon and acenocoumarol, respectively. At a willingness-to-pay threshold
      of ?20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be
      cost effective compared with the clinical dosing algorithm. CONCLUSION:
      Pharmacogenetic dosing improves health only slightly when compared with clinical
      dosing. However, availability of low-cost genotyping would make it a cost
      effective option.

PMID- 25616098
TI  - Impact of mineralocorticoid receptor polymorphisms on urinary electrolyte
      excretion with and without diuretic drugs.
AB  - AIM: Polymorphisms in the mineralocorticoid receptor may affect urinary sodium
      and potassium excretion. We investigated polymorphisms in the MR gene in relation
      to urinary electrolyte excretion in two separate studies. PATIENTS & METHODS: The
      genotype-phenotype association was studied in healthy volunteers after single
      doses of bumetanide, furosemide, torsemide, hydrochlorothiazide, triamterene and
      after NaCl restriction. RESULTS: High potassium excretion under all conditions
      except torsemide, and high NaCl excretion after bumetanide and furosemide were
      associated with the A allele of the intron-3 polymorphism (rs3857080). This
      polymorphism explained 5-10% of the functional variation and in vitro, rs3857080
      affected DNA binding of the transcription factor LHX4. CONCLUSION: rs3857080 may
      be a promising new candidate for research in cardiac and renal disorders and on
      antialdosteronergic drugs like spironolactone.

PMID- 25616099
TI  - P-glycoprotein: a clue to vitamin K antagonist stabilization.
AB  - BACKGROUND: Acenocoumarol is a vitamin K antagonist used in some European
      countries. As warfarin, this drug is characterized by a narrow therapeutic index
      and a large interindividual variability. AIM: The objective of this study was to
      assess the involvement of ABCB1 polymorphisms on acenocoumarol treatment.
      MATERIALS & METHODS: An observational cohort study was conducted to assess
      whether there is an association between the presence of the allelic variants of
      the ABCB1 gene coding for P-glycoprotein and acenocoumarol stabilization and
      daily doses during the first 35 days of treatment. RESULTS: One hundred and
      fifteen patients met the inclusion criteria. The results of the clinical study
      showed that carriers of ABCB1 c.3435TT were more rapidly stabilized than wild
      type patients (HR: 2.97, 95% CI: 1.23-7.18; p = 0.02). The same tendency was
      observed for the ABCB1 c.2677GT and 2677TT genotypes compared with ABCB1
      c.2677GG. The ABCB1 c.2677TT genotype was also associated with a significant
      increase in doses of acenocoumarol (p = 0.03), the same tendency was observed
      with the ABCB1 c.3435TT genotype compared with the wild-type patients.
      CONCLUSION: These data suggest that ABCB1 polymorphisms could be involved in the
      response to acenocoumarol treatment.

PMID- 25616100
TI  - Economic evaluation of pharmacogenomic-guided warfarin treatment for elderly
      Croatian atrial fibrillation patients with ischemic stroke.
AB  - BACKGROUND & METHODS: Economic evaluation in genomic medicine is an emerging
      discipline to assess the cost-effectiveness of genome-guided treatment. Here, we
      developed a pharmaco-economic model to assess whether pharmacogenomic (PGx)
      guided warfarin treatment of elderly ischemic stroke patients with atrial
      fibrillation in Croatia is cost effective compared with non-PGx therapy. The time
      horizon of the model was set at 1 year. RESULTS: Our primary analysis indicates
      that 97.07% (95% CI: 94.08-99.34%) of patients belonging to the PGx-guided group
      have not had any major complications, compared with the control group (89.12%;
      95% CI: 84.00-93.87%, p < 0.05). The total cost per patient was estimated at
      ?538.7 (95% CI: ?526.3-551.2) for the PGx-guided group versus ?219.7 (95% CI:
      ?137.9-304.2) for the control group. In terms of quality-adjusted life-years
      (QALYs) gained, total QALYs was estimated at 0.954 (95% CI: 0.943-0.964) and
      0.944 (95% CI: 0.931-0.956) for the PGx-guided and the control groups,
      respectively. The true difference in QALYs was estimated at 0.01 (95% CI: 0.005
      0.015) in favor of the PGx-guided group. The incremental cost-effectiveness ratio
      of the PGx-guided versus the control groups was estimated at ?31,225/QALY.
      CONCLUSION: Overall, our data indicate that PGx-guided warfarin treatment may
      represent a cost-effective therapy option for the management of elderly patients
      with atrial fibrillation who developed ischemic stroke in Croatia.

PMID- 25616101
TI  - Pharmacogenetics of chemotherapy-induced nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is associated with distressing
      adverse effects observed in patients during cytotoxic chemotherapy. One of the
      potential factors explaining suboptimal response to currently used antiemetics is
      variability in genes encoding enzymes and proteins that play a role in the action
      of antiemetic drugs. Pharmacogenomics studies of CINV are sparse and focus mainly
      on polymorphisms associated with serotonin receptor, drug metabolism and drug
      transport. Currently, the role of pharmacogenetics in mechanisms of CINV has not
      been fully unraveled, and it is premature to implement results of pharmacogenetic
      association studies of antiemetic drugs in clinical practice. More uniform
      studies, with genetic profiles and biomarkers relevant for the proposed target
      and transporter mechanisms, are needed. 

PMID- 25616102
TI  - Genetics and nonmelanoma skin cancer in kidney transplant recipients.
AB  - Kidney transplant recipients (KTRs) have a 65- to 250-fold greater risk than the
      general population of developing nonmelanoma skin cancer. Immunosuppressive drugs
      combined with traditional risk factors such as UV radiation exposure are the main
      modifiable risk factors for skin cancer development in transplant recipients.
      Genetic variation affecting immunosuppressive drug pharmacokinetics and
      pharmacodynamics has been associated with other transplant complications and may
      contribute to differences in skin cancer rates between KTRs. Genetic
      polymorphisms in genes encoding the prednisolone receptor, GST enzyme, MC1R,
      MTHFR enzyme and COX-2 enzyme have been shown to increase the risk of nonmelanoma
      skin cancer in KTRs. Genetic association studies may improve our understanding of
      how genetic variation affects skin cancer risk and potentially guide
      immunosuppressive treatment and skin cancer screening in at risk individuals. 

PMID- 25616103
TI  - Where should I send it? Optimizing the submission decision process.
AB  - How do scientists decide where to submit manuscripts? Many factors influence this
      decision, including prestige, acceptance probability, turnaround time, target
      audience, fit, and impact factor. Here, we present a framework for evaluating
      where to submit a manuscript based on the theory of Markov decision processes. We
      derive two models, one in which an author is trying to optimally maximize
      citations and another in which that goal is balanced by either minimizing the
      number of resubmissions or the total time in review. We parameterize the models
      with data on acceptance probability, submission-to-decision times, and impact
      factors for 61 ecology journals. We find that submission sequences beginning with
      Ecology Letters, Ecological Monographs, or PLOS ONE could be optimal depending on
      the importance given to time to acceptance or number of resubmissions. This
      analysis provides some guidance on where to submit a manuscript given the
      individual-specific values assigned to these disparate objectives. 

PMID- 25616104
TI  - Electrochemistry of a single attoliter emulsion droplet in collisions.
AB  - We report here the electrochemistry of emulsion droplets by observing single
      emulsion droplet collisions with selective electrochemical reduction on an
      ultramicroelectrode (UME). With appropriately applied potentials at an UME, we
      can observe the electrochemical effects of single collision signals from the
      complete electrolysis of single emulsion droplets, or selective electrolysis of
      redox species in single emulsion droplets. This was observed with nitrobenzene
      (NB), 7,7,8,8-tetracyanoquinodimethane (TCNQ), and ionic liquid. The NB, TCNQ,
      and ionic liquid act as emulsion material, redox specie, and emulsifier (and
      electrolyte), respectively. NB emulsions and NB (TCNQ) emulsions were made by
      ultrasonic processing. During the amperometric current-time (i-t) curve
      measurement with NB/water emulsion at -0.65 V, reduction of NB emulsion droplets
      was measured. In the case of less negative potentials, e.g., at -0.45 V with a NB
      (TCNQ) emulsion, selective reduction of TCNQ in NB droplet was measured. Spike
      like responses from electrolysis of NB or TCNQ in each experiment were observed.
      From these single-particle collision results of NB and NB (TCNQ) emulsions, the
      collision frequency, size distribution, i-t decay behavior of emulsion droplets,
      and possible mechanisms are discussed. 

PMID- 25616106
TI  - The detection of Propionibacterium acnes signatures in granulomas of lupus
      miliaris disseminatus faciei.
AB  - Lupus miliaris disseminatus faciei (LMDF) is a papular eruption that occurs on
      adults' faces, predominantly on the lower eyelids. Histologically, the
      granulomatous lesions are primarily situated around the hair follicles,
      particularly the superficial region/infundibula. Its etiology remains to be
      elucidated. Recently, Propionibacterium acnes (P. acnes) has been suspected as a
      cause of sarcoidosis. In light of the sarcoid-like reactions that are present in
      LMDF, we hypothesized that P. acnes may also be implicated in granulomas
      associated with the disease. We evaluated nine DNA samples from granulomatous
      lesions from the skin of patients with LMDF. We used laser capture
      microdissection to extract DNA from these regions. Polymerase chain reaction was
      performed to amplify segments of the 16S ribosomal RNA of P. acnes, and the P.
      acnes gene was clearly detectable in all nine DNA samples. The gene was also
      detected in samples from normal-appearing skin, but these bands were faint in all
      samples. The results of the present study suggest that P. acnes plays a
      pathogenetic roles in LMDF. 

PMID- 25616105
TI  - Airway epithelial NF-kappaB activation promotes the ability to overcome
      inhalational antigen tolerance.
AB  - BACKGROUND: Inhalational antigen tolerance typically protects against the
      development of allergic airway disease but may be overcome to induce allergic
      sensitization preceding the development of asthma. OBJECTIVES: We examined in
      vivo whether pre-existing inhalational antigen tolerance could be overcome by
      activation of the transcription factor NF-kappaB in conducting airway epithelial
      cells, and used a combination of in vivo and in vitro approaches to examine the
      mechanisms involved. METHODS: Wild-type and transgenic mice capable of expressing
      constitutively active IkappaB kinase beta (CAIKKbeta) in airway epithelium were
      tolerized to inhaled ovalbumin. Twenty-eight days later, the transgene was
      transiently expressed and mice were exposed to inhaled OVA on Day 30 in an
      attempt to overcome inhalational tolerance. RESULTS: Following ovalbumin
      challenge on days 40-42, CAIKKbeta mice in which the transgene had been activated
      exhibited characteristic features of allergic airway disease, including airway
      eosinophilia and methacholine hyper-responsiveness. Increases in the CD103(+) and
      CD11b(HI) lung dendritic cell populations were present in CAIKKbeta mice on Day
      31. Bronchoalveolar lavage from mice expressing CAIKKbeta mice induced CD4(+) T
      cells to secrete T(H)2 and T(H)17 cytokines, an effect that required IL-4 and IL
      1 signalling, respectively. CAIKKbeta mice on Dox demonstrated increased numbers
      of innate lymphoid type 2 cells (ILC2) in the lung, which also exhibited elevated
      mRNA expression of the T(H)2-polarizing cytokine IL-4. Finally, airway epithelial
      NF-kB activation induced allergic sensitization in CAIKKbeta mice on Dox that
      required IL-4 and IL-1 signalling in vivo. CONCLUSIONS: Our studies demonstrate
      that soluble mediators generated in response to airway epithelial NF-kappaB
      activation orchestrate the breaking of inhalational tolerance and allergic
      antigen sensitization through the effects of soluble mediators, including IL-1
      and IL-4, on pulmonary dendritic cells as well as innate lymphoid and CD4(+) T
      cells.

PMID- 25616107
TI  - Chromatin remodelling and autocrine TNFalpha are required for optimal interleukin
      6 expression in activated human neutrophils.
AB  - Controversy currently exists about the ability of human neutrophils to produce IL
      6. Here, we show that the chromatin organization of the IL-6 genomic locus in
      human neutrophils is constitutively kept in an inactive configuration. However,
      we also show that upon exposure to stimuli that trigger chromatin remodelling at
      the IL-6 locus, such as ligands for TLR8 or, less efficiently, TLR4, highly
      purified neutrophils express and secrete IL-6. In TLR8-activated neutrophils, but
      not monocytes, IL-6 expression is preceded by the induction of a latent enhancer
      located 14 kb upstream of the IL-6 transcriptional start site. In addition, IL-6
      induction is potentiated by endogenous TNFalpha, which prolongs the synthesis of
      the IkappaBzeta co-activator and sustains C/EBPbeta recruitment and histone
      acetylation at IL-6 regulatory regions. Altogether, these data clarify
      controversial literature on the ability of human neutrophils to generate IL-6 and
      uncover chromatin-dependent layers of regulation of IL-6 in these cells. 

PMID- 25616108
TI  - Overview of chitin metabolism enzymes in Manduca sexta: Identification, domain
      organization, phylogenetic analysis and gene expression.
AB  - Chitin is one of the most abundant biomaterials in nature. The biosynthesis and
      degradation of chitin in insects are complex and dynamically regulated to cope
      with insect growth and development. Chitin metabolism in insects is known to
      involve numerous enzymes, including chitin synthases (synthesis of chitin),
      chitin deacetylases (modification of chitin by deacetylation) and chitinases
      (degradation of chitin by hydrolysis). In this study, we conducted a genome-wide
      search and analysis of genes encoding these chitin metabolism enzymes in Manduca
      sexta. Our analysis confirmed that only two chitin synthases are present in M.
      sexta as in most other arthropods. Eleven chitin deacetylases (encoded by nine
      genes) were identified, with at least one representative in each of the five
      phylogenetic groups that have been described for chitin deacetylases to date.
      Eleven genes encoding for family 18 chitinases (GH18) were found in the M. sexta
      genome. Based on the presence of conserved sequence motifs in the catalytic
      sequences and phylogenetic relationships, two of the M. sexta chitinases did not
      cluster with any of the current eight phylogenetic groups of chitinases: two new
      groups were created (groups IX and X) and their characteristics are described.
      The result of the analysis of the Lepidoptera-specific chitinase-h (group h) is
      consistent with its proposed bacterial origin. By analyzing chitinases from
      fourteen species that belong to seven different phylogenetic groups, we reveal
      that the chitinase genes appear to have evolved sequentially in the arthropod
      lineage to achieve the current high level of diversity observed in M. sexta.
      Based on the sequence conservation of the catalytic domains and on their
      developmental stage- and tissue-specific expression, we propose putative
      functions for each group in each category of enzymes. 

PMID- 25616109
TI  - A novel strain of Cellulosimicrobium funkei can biologically detoxify aflatoxin
      B1 in ducklings.
AB  - Two experiments were conducted to screen microorganisms with aflatoxin B1 (AFB1 )
      removal potential from soils and to evaluate their ability in reducing the toxic
      effects of AFB1 in ducklings. In experiment 1, we screened 11 isolates that
      showed the AFB1 biodegradation ability, and the one exhibited the highest AFB1
      removal ability (97%) was characterized and identified as Cellulosimicrobium
      funkei (C. funkei). In experiment 2, 80 day-old Cherry Valley ducklings were
      divided into four groups with four replicates of five birds each and were used in
      a 2 by 2 factorial trial design, in which the main factors included
      administration of AFB1 versus solvent and C. funkei versus solvent for 2 weeks.
      The AFB1 treatment significantly decreased the body weight gain, feed intake and
      impaired feed conversion ratio. AFB1 also decreased serum albumin and total
      protein concentration, while it increased activities of alanine aminotransferase
      and aspartate aminotransferase and liver damage in the ducklings. Supplementation
      of C. funkei alleviated the adverse effects of AFB1 on growth performance, and
      provided protective effects on the serum biochemical indicators, and decreased
      hepatic injury in the ducklings. Conclusively, our results suggest that the novel
      isolated C. funkei strain could be used to mitigate the negative effects of
      aflatoxicosis in ducklings. 

PMID- 25616110
TI  - A gamma-cyclodextrin duplex connected with two disulfide bonds: synthesis,
      structure and inclusion complexes.
AB  - Per(2,3,6-tri-O-benzyl)-gamma-cyclodextrin was debenzylated by DIBAL-H to produce
      a mixture of C6(I),C6(IV) and C6(I),C6(V) isomeric diols, which were separated
      and isolated. The C2-symmetrical C6(I),C6(V) diol was transformed into dithiol
      and dimerized to produce a gamma-cyclodextrin duplex structure. A crystal
      structure revealed tubular cavity whose peripheries are slightly elliptically
      distorted. The solvent accessible volume of the cavity of the gamma-CD duplex is
      about 740 A(3). Due to this large inner space the duplex forms very stable
      inclusion complexes with steroids; bile acids examined in this study show binding
      affinities to the gamma-cyclodextrin duplex in the range of 5.3 * 10(7) M(-1)-1.9
      * 10(8) M(-1). 

PMID- 25616111
TI  - Impact of inhibitors on hemophilia A mortality in the United States.
AB  - The previously published mortality studies are limited in hemophilia populations
      but suggest that there is no increased risk of mortality in factor VIII inhibitor
      patients. This retrospective study analyzed surveillance data collected on 7,386
      males with severe hemophilia A over a 13-year period to assess the association
      between a current inhibitor and death. During the study period, 432 participants
      died, among whom 48 were patients with an inhibitor. Clinical characteristics
      most strongly associated with death were increased number of reported bleeds,
      signs of liver disease, infection with either HIV or HCV, and the presence of
      inhibitor. Patients who underwent successful tolerization were not considered
      inhibitor patients in our analysis. In a multivariable analysis, the odds of
      death were 70% higher among patients with a current inhibitor compared to those
      without an inhibitor (P < 0.01). Deaths among patients with inhibitors were much
      more likely to be attributed to bleeding complications than those among patients
      without an inhibitor (42 vs. 12%, P < 0.0001). We conclude that males with severe
      hemophilia A and a current inhibitor are at increased risk of death.

PMID- 25616112
TI  - Selection for tameness, a key behavioral trait of domestication, increases adult
      hippocampal neurogenesis in foxes.
AB  - Work on laboratory and wild rodents suggests that domestication may impact on the
      extent of adult hippocampal neurogenesis and its responsiveness to regulatory
      factors. There is, however, no model of laboratory rodents and their
      nondomesticated conspecifics that would allow a controlled comparison of the
      effect of domestication. Here, we present a controlled within-species comparison
      of adult hippocampal neurogenesis in farm-bred foxes (Vulpes vulpes) that differ
      in their genetically determined degree of tameness. Quantitative comparisons of
      cell proliferation (Ki67) and differentiating cells of neuronal lineage
      (doublecortin, DCX) in the hippocampus of foxes were performed as a proxy for
      neurogenesis. Higher neurogenesis was observed in tameness-selected foxes,
      notably in an extended subgranular zone of the middle and temporal compartments
      of the hippocampus. Increased neurogenesis is negatively associated with
      aggressive behavior. Across all animals, strong septotemporal gradients were
      found, with higher numbers of proliferating cells and young neurons relative to
      resident granule cells in the temporal than in the septal hippocampus. The
      opposite gradient was found for the ratio of DCX/Ki67- positive cells. When
      tameness-selected and unselected foxes are compared with rodents and primates,
      proliferation is similar, while the number of young neurons is higher. The
      difference may be mediated by an extended period of differentiation or higher
      rate of survival. On the background of this species-specific neurogenic pattern,
      selection of foxes for a single behavioral trait key to domestication, i.e.,
      genetic tameness, is accompanied by global and region-specific increases in
      neurogenesis.

PMID- 25616113
TI  - Position along the nasal/temporal plane affects synaptic development by adult
      photoreceptors, revealed by micropatterning.
AB  - In retinal degeneration, death of photoreceptors causes blindness. Repair of the
      retina by transplanting photoreceptors has resulted in limited functional
      connectivity between transplanted and host neurons. We hypothesize that absence
      of appropriate biological cues, specifically positional (retinotopographic) cues,
      reduces synaptogenesis. Here we use micropatterning to test whether regional
      origin affects the early synaptic development of photoreceptors. Right and left
      retinas from salamanders were first labelled with dextran tetramethyl-rhodamine
      and fluorescein, respectively, bisected into nasal (N)/temporal (T) or dorsal
      (D)/ventral (V) halves, individually dissociated, mixed, and cultured for 1 week.
      Origin of cells was identified by the fluorescent label. Interactions between
      photoreceptors and neighboring (target) cells were assessed by the number of
      neuritic contacts with a presynaptic swelling (varicosity). Randomly-plated
      photoreceptors showed no preference for cellular origin, likely due to multiple
      potential interactions available to each cell. To reduce cell-cell interactions,
      culture substrate was patterned using a microfluidic device with 10 MUm-wide
      channels separated by 200 MUm, thus allowing only 1-2 targets per photoreceptor.
      In patterned cultures, 36.89% of N rod cells contacted T targets but only 27.42%
      of N rod cells contacted N targets; similarly 35.05% of T rod cells contacted N
      cells but only 17.08% contacted T cells. Thus, opposite regions were more
      permissive of contact. However, neither cone nor D/V rod cells showed preferences
      for positional origin of targets. In conclusion, micropatterning demonstrated
      that neuritic differentiation by rod cells depends on retinotopographic cues
      along the nasal/temporal plane, suggesting that transplanting rod cells of known
      positional origin will increase transplant success. 

PMID- 25616114
TI  - Hydrogel-coated feed spacers in two-phase flow cleaning in spiral wound membrane
      elements: a novel platform for eco-friendly biofouling mitigation.
AB  - Biofouling is still a major challenge in the application of nanofiltration and
      reverse osmosis membranes. Here we present a platform approach for
      environmentally friendly biofouling control using a combination of a hydrogel
      coated feed spacer and two-phase flow cleaning. Neutral (polyHEMA-co-PEG10MA),
      cationic (polyDMAEMA) and anionic (polySPMA) hydrogels have been successfully
      grafted onto polypropylene (PP) feed spacers via plasma-mediated UV
      polymerization. These coatings maintained their chemical stability after 7 days
      incubation in neutral (pH 7), acidic (pH 5) and basic (pH 9) environments. Anti
      biofouling properties of these coatings were evaluated by Escherichia coli
      attachment assay and nanofiltration experiments at a TMP of 600 kPag using tap
      water with additional nutrients as feed and by using optical coherence
      tomography. Especially the anionic polySPMA-coated PP feed spacer shows reduced
      attachment of E. coli and biofouling in the spacer-filled narrow channels
      resulting in delayed biofilm growth. Employing this highly hydrophilic coating
      during removal of biofouling by two-phase flow cleaning also showed enhanced
      cleaning efficiency, feed channel pressure drop and flux recoveries. The strong
      hydrophilic nature and the presence of negative charge on polySPMA are most
      probably responsible for the improved antifouling behavior. A combination of
      polySPMA-coated PP feed spacers and two-phase flow cleaning therefore is
      promising and an environmentally friendly approach to control biofouling in NF/RO
      systems employing spiral-wound membrane modules. 

PMID- 25616115
TI  - Feasibility of sulfide control in sewers by reuse of iron rich drinking water
      treatment sludge.
AB  - Dosage of iron salt is the most commonly used method for sulfide control in sewer
      networks but incurs high chemical costs. In this study, we experimentally
      investigate the feasibility of using iron rich drinking water treatment sludge
      for sulfide control in sewers. A lab-scale rising main sewer biofilm reactor was
      used. The sulfide concentration in the effluent decreased from 15.5 to 19.8 mgS/L
      (without dosing) to below 0.7-2.3 mgS/L at a sludge dosing rate achieving an iron
      to total dissolved inorganic sulfur molar ratio (Fe:S) of 1:1, with further
      removal of sulfide possible by prolonging the reaction time. In fact, batch tests
      revealed an Fe consumption to sulfide removal ratio of 0.5 +/- 0.02 (mole:mole),
      suggesting the possible occurrence of other reactions involving the removal of
      sulfide. Modelling revealed that the reaction between iron in sludge and sulfide
      has reaction orders of 0.65 +/- 0.01 and 0.77 +/- 0.02 with respect to the Fe and
      sulfide concentrations, respectively. The addition of sludge slightly increased
      the total chemical oxidation demand (tCOD) concentration (by approximately 12%)
      as expected, but decreased the soluble chemical oxidation demand (sCOD)
      concentration and methane formation by 7% and 20%, respectively. Some phosphate
      removal (13%) was also observed at the sludge dosing rate of 1:1 (Fe:S), which is
      beneficial to nutrient removal from the wastewater. Overall, this study suggests
      that dosing iron-rich drinking water sludge to sewers could be an effective
      strategy for sulfide removal in sewer systems, which would also reduce the sludge
      disposal costs for drinking water treatment works. However, its potential side
      effects on sewer sedimentation and on the wastewater treatment plant effluent
      remain to be investigated. 

PMID- 25616116
TI  - Phosphorus losses from agricultural land to natural waters are reduced by
      immobilization in iron-rich sediments of drainage ditches.
AB  - Redox reactions involving iron (Fe) strongly affect the mobility of phosphorus
      (P) and its migration from agricultural land to freshwater. We studied the
      transfer of P from groundwater to open drainage ditches in an area where, due to
      Fe(II) rich groundwater, the sediments of these ditches contain accumulated Fe
      oxyhydroxides. The average P concentrations in the groundwater feeding two out of
      three studied drainage ditches exceeded environmental limits for freshwaters by
      factors 11 and 16, but after passing through the Fe-rich sediments, the P
      concentrations in the ditch water were below these limits. In order to identify
      the processes which govern Fe and P mobility in these systems, we used diffusive
      equilibration in thin films (DET) to measure the vertical concentration profiles
      of P and Fe in the sediment pore water and in the ditchwater. The Fe
      concentrations in the sediment pore water ranged between 10 and 200 mg L(-1) and
      exceeded those in the inflowing groundwater by approximately one order of
      magnitude, due to reductive dissolution of Fe oxyhydroxides in the sediment. The
      dissolved P concentrations only marginally increased between groundwater and
      sediment pore water. In the poorly mixed ditchwater, the dissolved Fe
      concentrations decreased towards the water surface due to oxidative precipitation
      of fresh Fe oxyhydroxides, and the P concentrations decreased more sharply than
      those of Fe. These observations support the view that the dynamics of Fe and P
      are governed by reduction reactions in the sediment and by oxidation reactions in
      the ditchwater. In the sediment, reductive dissolution of P-containing Fe
      oxyhydroxides causes more efficient solubilization of Fe than of P, likely
      because P is buffered by adsorption on residual Fe oxyhydroxides. Conversely, in
      the ditchwater, oxidative precipitation causes more efficient immobilization of P
      than of Fe, due to ferric phosphate formation. The combination of these processes
      yields a natural and highly efficient sink for P. It is concluded that, in Fe
      rich systems, the fate of P at the sediment-water interface is determined by
      reduction and oxidation of Fe. 

PMID- 25616118
TI  - alpha-Amylase-assisted extraction of polysaccharides from Panax ginseng.
AB  - In this paper, alpha-amylase-assisted extraction was used to isolate the
      polysaccharide that remained in hot water-extracted ginseng. The yield of the
      polysaccharide was 9.0%, almost equal to that of the hot water-extracted
      polysaccharide. Using anion exchange and gel permeation chromatography, the
      polysaccharide was fractionated into a neutral polysaccharide fraction and six
      pectic fractions. The neutral fraction accounted for 76% of the polysaccharide
      and contained both amylopectin and amylose. The pectic polysaccharide fractions
      were identified to be arabinogalactan, type-I rhamnogalacturonan and
      homogalacturonan-type pectin by high-performance liquid chromatography, Fourier
      transform-infrared and nuclear magnetic resonance analysis. Structural and
      lymphocyte proliferation activity results showed that these polysaccharides were
      different from those extracted by hot water, indicating that ginseng contains
      complex polysaccharides with diverse structures, which results in its diverse
      pharmacological activities. The alpha-amylase-assisted extraction is a novel
      method for preparing ginseng polysaccharides and could be applied toward the
      further study and exploration of ginseng. These findings provide technical and
      theoretical support for ginseng pharmacology. 

PMID- 25616117
TI  - Vascular effects of aerobic exercise training in rat adult offspring exposed to
      hypoxia-induced intrauterine growth restriction.
AB  - KEY POINTS: Prenatal hypoxia, one of the most common consequences of complicated
      pregnancies, leads to intrauterine growth restriction (IUGR) and impairs later
      life endothelium-dependent vascular function. Early interventions are needed to
      ultimately reduce later-life risk for cardiovascular disease. Aerobic exercise
      training has been shown to prevent cardiovascular diseases. Whether exercise can
      be used as an intervention to reverse the vascular phenotype of this susceptible
      population is unknown. Aerobic exercise training enhanced endothelium-derived
      hyperpolarization-mediated vasodilatation in gastrocnemius muscle arteries in
      male IUGR offspring, and did not improve nitric oxide-mediated vasodilatation in
      IUGR offspring. Understanding the mechanisms by which exercise impacts the
      cardiovascular system in a susceptible population and the consideration of sexual
      dimorphism is essential to define whether exercise could be used as a preventive
      strategy in this population. ABSTRACT: Hypoxia in utero is a critical insult
      causing intrauterine growth restriction (IUGR). Adult offspring born with hypoxia
      induced IUGR have impaired endothelium-dependent vascular function. We tested
      whether aerobic exercise improves IUGR-induced endothelial dysfunction. Pregnant
      Sprague-Dawley rats were exposed to control (21% oxygen) or hypoxic (11% oxygen)
      conditions from gestational day 15 to 21. Male and female offspring from normoxic
      and hypoxic (IUGR) pregnancies were randomized at 10 weeks of age to either an
      exercise-trained or sedentary group. Exercise-trained rats ran on a treadmill for
      30 min at 20 m min(-1) , 5 deg gradient, 5 days week(-1) , for 6 weeks.
      Concentration-response curves to phenylephrine and methylcholine were performed
      in second order mesenteric and gastrocnemius muscle arteries, in the presence or
      absence of l-NAME (100 MUm), MnTBAP (peroxynitrite scavenger; 10 MUm), apamin
      (0.1 MUm) and TRAM-34 (an intermediate-conductance calcium-activated potassium
      channel blocker; 10 MUm), or indomethacin (5 MUm). In adult male IUGR offspring,
      prenatal hypoxia had no effect on total vasodilator responses in either vascular
      bed. Aerobic exercise training in IUGR males, however, improved endothelium
      derived hyperpolarization (EDH)-mediated vasodilatation in gastrocnemius muscle
      arteries. Female IUGR offspring had reduced NO-mediated vasodilatation in both
      vascular beds, along with decreased total vasodilator responses and increased
      prostaglandin-mediated vasoconstriction in gastrocnemius muscle arteries. In
      contrast to males, aerobic exercise training in IUGR female offspring had no
      effect on either vascular bed. Exercise may not prove to be a beneficial therapy
      for specific vascular pathways affected by prenatal hypoxia, particularly in
      female offspring.

PMID- 25616119
TI  - Isolation and structural features of an antiradical polysaccharide of Capsicum
      annuum that interacts with BSA.
AB  - Red peppers, Capsicum annuum, are used worldwide as spices, foods and medicines.
      Herein, we have analyzed an antiradical polysaccharide isolated from red peppers
      through successive acetate buffer extraction. This macromolecule was purified
      using graded precipitation with ethanol, alpha-amylase treatment, deproteination
      and anion-exchange chromatography. This highly-branched polysaccharide (360 kDa)
      was esterified with phenolic acids and contained a (1,3)-linked-beta-Galp chain
      substituted at O-6 by (1,6)-linked-beta-Galp residues. The latter was substituted
      at O-3 by (1,5)- and (1,3,5)-linked-alpha-Araf residues, and non-reducing end
      units of alpha-Araf and beta-Galp. The antiradical potential of this
      polysaccharide was comparable to standard antioxidants. The phenolic acid
      residues were the functional sites. This polysaccharide could form complex with
      bovine serum albumin having binding constant K = 5.24 * 10(6)/M and change its
      microenvironment. Thus, aqueous extraction method provides a macromolecule that
      stimulates biological responses; this emphasizes the significance of red pepper
      as dietary antioxidant.

PMID- 25616120
TI  - The congruency sequence effect emerges when the distracter precedes the target.
AB  - The congruency effect in distracter interference tasks is typically smaller when
      the previous trial was incongruent as compared to congruent, suggesting the
      operation of a control process that minimizes the influence of irrelevant stimuli
      on behavior. However, both the conditions under which this congruency sequence
      effect (CSE) can be most easily observed without the typical learning and memory
      confounds, and the control process underlying it, remain controversial. We
      therefore tested a recent hypothesis that the CSE is most easily observed without
      the typical confounds when the distracter is processed before the target. In line
      with this "distracter head start" hypothesis, in Experiments 1 and 2 the CSE was
      larger when the distracter appeared before, relative to with, the target.
      Further, in Experiment 3, we observed a negative congruency effect after
      incongruent trials when a long interval separated the distracter from the target,
      consistent with a modulation of the response engendered by the distracter but not
      with a shift of attention toward the target. These findings reveal an important
      determinant of CSE magnitude when the typical learning and memory confounds are
      absent and new insights into the nature of control processes that contribute to
      this phenomenon. 

PMID- 25616121
TI  - N,N-diethylurea-catalyzed amidation between electron-deficient aryl azides and
      phenylacetaldehydes.
AB  - Urea structures, of which N,N-diethylurea (DEU) proved to be the most efficient,
      were discovered to catalyze amidation reactions between electron-deficient aryl
      azides and phenylacetaldehydes. Experimental data support 1,3-dipolar
      cycloaddition between DEU-activated enols and electrophilic phenyl azides,
      especially perfluoroaryl azides, followed by rearrangement of the triazoline
      intermediate. The activation of the aldehyde under near-neutral conditions was of
      special importance in inhibiting dehydration/aromatization of the triazoline
      intermediate, thus promoting the rearrangement to form aryl amides. 

PMID- 25616122
TI  - Systematic review: patient-reported outcomes in chronic hepatitis C--the impact
      of liver disease and new treatment regimens.
AB  - BACKGROUND: Treatment for chronic hepatitis C (CH-C) is rapidly changing and
      moving away from an interferon and ribavirin-based therapy to interferon-free
      ribavirin-free all oral regimens. These regimens are simpler and shorter to
      administer with very high efficacy rates and better side effect profiles. As
      advances in the treatment of CH-C occur, it is imperative to capture both
      clinical outcomes (efficacy and safety) as well as patient-reported outcomes
      (PROs). In fact, PROs assesses and quantifies the impact of these regimens on
      patient experience. PROs assess patients' health-related quality of life (HRQOL)
      especially in the realms of fatigue and neuropsychiatric issues such as
      depression which can affect treatment adherence and work productivity. AIM: To
      review the literature related to PRO's in HCV patients and summarise the impact
      of CH-C and its treatment on PROs. METHODS: Databases Ovid MEDLINE and PubMed
      were searched from 1990 to October 2014 using a combination of MEsh, thesaurus
      terms and relevant text words: hepatitis C, CH-C, treatment, quality of life,
      health-related quality of life, fatigue, work productivity, adherence, patient
      reported outcomes, direct acting anti-viral agents and second generation direct
      acting anti-viral agents. Each manuscript was assessed for pertinence to the
      issue of PROs in CH-C as well as the quality of study design and publications.
      RESULTS: From the literature, it is evident that CH-C patients have baseline PRO
      impairment. Furthermore, treatment with interferon with or without ribavirin and
      first generation DAAs causes additional PRO burden which can negatively impact
      treatment adherence and indirectly, treatment efficacy and work productivity. The
      new treatment regimens with interferon- and ribavirin-free regimens not only have
      very high efficacy, but also result in the improvement of PRO scores as early as
      2 weeks into treatment as well as possibly better adherence to treatment
      regimens. CONCLUSIONS: CH-C and its treatment have been associated with patient
      reported outcome impairment. The new IF-free and RBV-free regimens are associated
      with high efficacy and substantial improvement of patient-reported outcomes in
      clinical trial setting. Although very encouraging, more data are needed to assess
      patient-reported outcomes, adherence and work productivity of CH-C patients in
      the real world setting of clinical practice.

PMID- 25616124
TI  - IV access service provision.

PMID- 25616123
TI  - Genetics of myocarditis in arrhythmogenic right ventricular dysplasia.
AB  - BACKGROUND: Myocarditis occasionally is related to arrhythmogenic right
      ventricular dysplasia (ARVD) and sometimes overlaps during the early stages,
      which may lead to misdiagnosis. Acute myocarditis may reflect an active phase of
      ARVD. OBJECTIVE: The purpose of this study was to evaluate the genetic basis of
      myocarditis in ARVD and to investigate the association with a poorer prognosis
      and a higher risk of ventricular arrhythmias. METHODS: Two groups were analyzed:
      group A, which consisted of 131 affected patients-84 with ARVD (62% male, age 45
      years [range 33-55 years]) and 47 with left-sided forms (arrhythmogenic left
      ventricular dysplasia [ALVD]) (47% male, age 45 years [range 25-61 years]); and
      group B, which consisted of 64 nonaffected mutation-carrying relatives (36% male,
      age 42 years [range 22-56 years]; 23 from classic ARVD families and 41 from ALVD
      families). RESULTS: Seven patients (3.5%) presented with a clinical diagnosis of
      acute myocarditis over median follow-up of 34 months. Myocarditis was the first
      clinical presentation in 6 of 7 cases. In 2 patients, acute myocarditis preceded
      worsening of left ventricular systolic function. In 1 case, myocarditis was
      associated with an increased gadolinium pattern in cardiac magnetic resonance.
      Two patients presented with ECG changes weeks after myocarditis resolution.
      Myocarditis preceded the development of ventricular tachycardia in 2 other
      patients. Myocarditis clustered in families bearing DSP Q447* and LDB3 c.1051A>G.
      CONCLUSION: Acute myocarditis reflects an active phase of ARVD that leads to
      changes in phenotype and abrupt progression of the disease. An active phase
      should be suspected in a patient with myocarditis associated with a family
      history of ARVD. Certain mutations may increase the susceptibility to
      superimposed myocarditis in ARVD.

PMID- 25616125
TI  - Routine versus clinically indicated replacement of peripheral catheters.

PMID- 25616126
TI  - Recognising air embolism as a complication of vascular access.

PMID- 25616127
TI  - Promoting safe IV management in practice using H.A.N.D.S.
AB  - The aim of this article is to promote best practice for the insertion and care of
      intravascular (IV) devices. The H.A.N.D.S. acronym was created to serve as an
      aide memoire to general and specialist nurses regarding the 5 key interventions
      to prevent catheter-related bloodstream infections (CRBSIs). In order to promote
      safe and evidence-based practice in IV therapy a practical guide with clinical
      information about common IV procedures has been developed. This article provides
      back-to-basics guidance on how to deliver IV therapy safely and effectively. 

PMID- 25616128
TI  - Whose line is it anyway?

PMID- 25616129
TI  - Experiences of the first PICC team in the Czech Republic.
AB  - The first specialist nursing team placing peripherally inserted central catheters
      (PICCs) in the Czech Republic was established in September 2012. During 2013 the
      team placed 167 PICCs and 162 midline catheters. In another 6 patients the
      insertion was not successful. PICCs were inserted mainly for oncology patients;
      while midline catheters were inserted for patients admitted to general wards.
      Average duration of catheter insertion was 91 days (range 7-285 days) for PICCs
      and 14 days (range 2-40 days) for midline catheters. During follow up of PICCs,
      catheter infection rate was 0.3/1000 days, vein thrombosis rate 0.4/1000 days,
      catheter occlusion 0.4/1000 days, and catheter displacement 0.33/1000 days. For
      midline catheters infection rate was 1.4/1000 days, vein thrombosis 5.2/1000
      days, catheter occlusion 2.6/1000 days, and catheter displacement 2.2/1000 days.
      The authors hope that these results will motivate other hospitals in the Czech
      republic to establish PICC teams, as in other European countries. 

PMID- 25616130
TI  - Operando X-ray scattering and spectroscopic analysis of germanium nanowire anodes
      in lithium ion batteries.
AB  - X-ray diffraction (XRD) and Fourier transform extended X-ray absorption fine
      structure (EXAFS) analysis of X-ray absorption spectroscopy (XAS) measurements
      have been employed to determine structural and bonding changes, as a function of
      the lithium content/state of charge, of germanium nanowires used as the active
      anode material within lithium ion batteries (LIBs). Our data, collected
      throughout the course of battery cycling (operando), indicate that lithium
      incorporation within the nanostructured germanium occurs heterogeneously,
      preferentially into amorphous regions over crystalline domains. Maintenance of
      the molecular structural integrity within the germanium nanowire is dependent on
      the depth of discharge. Discharging to a shallower cutoff voltage preserves
      partial crystallinity for several cycles. 

PMID- 25616131
TI  - Computational identification of epigenetically regulated lncRNAs and their
      associated genes based on integrating genomic data.
AB  - Long non-coding RNAs (lncRNAs) are new players in various biological processes.
      However, understanding of lncRNAs is still in its infancy. Here, we proposed an
      integrative method to identify epigenetically regulated lncRNAs and their
      associated genes. By combining RNA-seq data and ChIP-seq data for histone H3
      trimethylated at lysine 4 (H3K4me3) and H3K27me3, we identified 699 H3K4me3
      regulated and 235 H3K27me3-regulated lncRNAs, each with an average of 238 and 307
      associated genes, respectively. By analyzing Polycomb repressive complex 2 (PRC2)
      binding maps, we observed that the negatively related genes of most
      epigenetically regulated lncRNAs were enriched for PRC2-binding genes. In
      addition, through enrichment analysis, we inferred some lncRNAs with aberrant
      epigenetic modifications in glioblastoma and Alzheimer's disease. Together, we
      describe a method for the analysis of lncRNAs and demonstrate how integration of
      multi-omics data can improve understanding of lncRNAs. 

PMID- 25616132
TI  - RIP140 triggers foam-cell formation by repressing ABCA1/G1 expression and
      cholesterol efflux via liver X receptor.
AB  - Receptor-interacting protein 140 (RIP140) is a multifunctional coregulator of
      lipid metabolism and inflammation. However, the potential role of RIP140 in
      atherosclerosis remains unknown. The present study investigated the impact of
      RIP140 on foam cell formation, a critical step in pathogenesis of
      atherosclerosis. The expression of RIP140 was increased in foam cells. RIP140
      overexpression resulted in decreased cholesterol efflux in macrophages and their
      concomitant differentiation into foam cells. Moreover, RIP140 negatively
      regulated the macrophage expression of ATP-binding cassette transporters A1 and
      G1 (ABCA1/G1), by suppressing the expression and activity of liver X receptor
      (LXR). These findings shed light onto the contribution of RIP140 to the
      development and progression of atherosclerosis, and suggest a novel therapeutic
      target for the treatment of atherosclerosis. 

PMID- 25616133
TI  - c-MYB regulates cell growth and DNA damage repair through modulating MiR-143.
AB  - Radiotherapy is the most successful nonsurgical treatment for nasopharyngeal
      carcinoma (NCP). Although NPCs initially respond well to a full course of
      radiation, recurrence and metastasis are frequent. In this study, we found that
      down-regulated c-MYB expression was associated with increased radiation
      resistance and DNA damage repair ability. Interestingly, c-MYB was over-expressed
      in cancer tissues but not in the adjacent tissues. Down-regulation of c-MYB
      expression inhibited cell proliferation, and led to cell cycle arrest at the M
      phase in NPC cells. Luciferase and chromatin immunoprecipitation assays
      demonstrated that c-MYB transactivated miR-143 through direct binding to its
      promoter. Based on these results, c-MYB might target miR-143 in order to regulate
      stem cell properties, cell growth, apoptosis, and DNA damage repair. 

PMID- 25616134
TI  - Spectroscopic separation of (13) C NMR spectra of complex isomeric mixtures by
      the CSSF-TOCSY-INEPT experiment.
AB  - Isomeric mixtures from synthetic or natural origins can pose fundamental
      challenges for their chromatographic separation and spectroscopic identification.
      A novel 1D selective NMR experiment, chemical shift selective filter (CSSF)-TOCSY
      INEPT, is presented that allows the extraction of (13) C NMR subspectra of
      discrete isomers in complex mixtures without physical separation. This is
      achieved via CSS excitation of proton signals in the (1) H NMR mixture spectrum,
      propagation of the selectivity by polarization transfer within coupled (1) H
      spins, and subsequent relaying of the magnetization from (1) H to (13) C by
      direct INEPT transfer to generate (13) C NMR subspectra. Simple consolidation of
      the subspectra yields (13) C NMR spectra for individual isomers. Alternatively,
      CSSF-INEPT with heteronuclear long-range transfer can correlate the isolated
      networks of coupled spins and therefore facilitate the reconstruction of the (13)
      C NMR spectra for isomers containing multiple spin systems. A proof-of-principle
      validation of the CSSF-TOCSY-INEPT experiment is demonstrated on three mixtures
      with different spectral and structural complexities. The results show that CSSF
      TOCSY-INEPT is a versatile, powerful tool for deconvoluting isomeric mixtures
      within the NMR tube with unprecedented resolution and offers unique, unambiguous
      spectral information for structure elucidation.

PMID- 25616136
TI  - Dispersal dynamics in food webs.
AB  - Studies of food webs suggest that limited nonrandom dispersal can play an
      important role in structuring food webs. It is not clear, however, whether
      density-dependent dispersal fits empirical patterns of food webs better than
      density-independent dispersal. Here, we study a spatially distributed food web,
      using a series of population-dispersal models that contrast density-independent
      and density-dependent dispersal in landscapes where sampled sites are either
      homogeneously or heterogeneously distributed. These models are fitted to
      empirical data, allowing us to infer mechanisms that are consistent with the
      data. Our results show that models with density-dependent dispersal fit the
      alpha, beta, and gamma tritrophic richness observed in empirical data best. Our
      results also show that density-dependent dispersal leads to a critical distance
      threshold beyond which site similarity (i.e., beta tritrophic richness) starts to
      decrease much faster. Such a threshold can also be detected in the empirical
      data. In contrast, models with density-independent dispersal do not predict such
      a threshold. Moreover, preferential dispersal from more centrally located sites
      to peripheral sites does not provide a better fit to empirical data when compared
      with symmetric dispersal between sites. Our results suggest that nonrandom
      dispersal in heterogeneous landscapes is an important driver that shapes local
      and regional richness (i.e., alpha and gamma tritrophic richness, respectively)
      as well as the distance-decay relationship (i.e., beta tritrophic richness) in
      food webs.

PMID- 25616135
TI  - Estimating the cost-effectiveness of pre-exposure prophylaxis to reduce HIV-1 and
      HSV-2 incidence in HIV-serodiscordant couples in South Africa.
AB  - OBJECTIVE: To estimate the cost-effectiveness of daily oral tenofovir-based PrEP,
      with a protective effect against HSV-2 as well as HIV-1, among HIV-1
      serodiscordant couples in South Africa. METHODS: We incorporated HSV-2
      acquisition, transmission, and interaction with HIV-1 into a microsimulation
      model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of
      PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1
      1infected partner, and for one year thereafter. RESULTS: We estimate the cost per
      disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP
      has no effect on reducing HSV-2 acquisition, and one in which there is a 33%
      reduction. After a twenty-year intervention, the cost per DALY averted is
      estimated to be $10,383 and $9,757, respectively--a 6% reduction, given the
      additional benefit of reduced HSV-2 acquisition. If all couples are discordant
      for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows
      that the impact is limited by HSV-2 concordance in couples. CONCLUSION: After a
      20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is
      estimated to be modestly lower than without any effect, providing an increase of
      health benefits in addition to HIV-1 prevention at no extra cost. The small
      degree of the effect is in part due to a high prevalence of HSV-2 infection in
      HIV-1 serodiscordant couples in South Africa.

PMID- 25616137
TI  - Abiotic, biotic, and evolutionary control of the distribution of C and N isotopes
      in food webs.
AB  - Ecosystem functioning depends on nutrient cycles and their responses to abiotic
      and biotic determinants, with the influence of evolutionary legacies being
      generally overlooked in ecosystem ecology. Along a broad elevation gradient
      characterized by shifting climatic and grazing environments, we addressed clines
      of plant N and C?N content and of delta(13)C and delta(15)N in producers (herbs)
      and in primary (grasshoppers) and secondary (birds) consumers, both within and
      between species in phylogenetically controlled scenarios. We found parallel and
      significant intra- and interspecific trends of isotopic variation with elevation
      in the three groups. In primary producers, nutrient and isotope distributions had
      a detectable phylogenetic signal that constrained their variation along the
      environmental gradient. The influence of the environment could not be ascribed to
      any single factor, and both grazing and climate had an effect on leaf
      stoichiometry and, thus, on the resources available to consumers. Trends in
      consumers matched those in plants but often became nonsignificant after
      controlling for isotopic values of their direct resources, revealing direct
      bottom-up control and little phylogenetic dependence. By integrating ecosystem
      and mechanistic perspectives, we found that nutrient dynamics in food webs are
      governed at the base by the complex interaction between local determinants and
      evolutionary factors.

PMID- 25616138
TI  - Metapopulation dynamics on ephemeral patches.
AB  - A challenge for conservation management is to understand how population and
      habitat dynamics interact to affect species persistence. In real landscapes,
      timing and duration of disturbances can vary, and species' responses to habitat
      changes will depend on how timing of dispersal and reproduction events relate to
      the landscape temporal structure. For instance, increasing disturbance frequency
      may promote extinction of species that are unable to appropriately time their
      reproduction in an ever-changing habitat and favor species that are able to track
      habitat changes. We developed a mathematical model to compare the effects of
      pulsed dispersal, initiated by shifts in habitat quality, with temporally
      continuous dispersal. We tested the effects of habitat (and population) turnover
      rates on metapopulation establishment, persistence, and long-term patch
      occupancy. Pulsed dispersal reduced patch occupancy and metapopulation longevity
      when habitat patches are relatively permanent. In such cases, demographic
      extinction was the primary form of local extinction. Conversely, when habitat
      patches are short-lived and new ones are frequently formed, pulsed dispersal
      promoted rapid colonization, increased occupancy, and prolonged metapopulation
      persistence. Our results show that species responsiveness to habitat disturbance
      is critical to metapopulation persistence, having profound implications for the
      species likely to persist in landscapes with altered disturbance regimes.

PMID- 25616139
TI  - Marine population connectivity: reconciling large-scale dispersal and high self
      retention.
AB  - Predicting connectivity patterns in systems with fluid transport requires
      descriptions of the spatial distribution of propagules. In contrast to research
      on terrestrial seed dispersal, where much attention has focused on localized
      physical factors affecting dispersal, studies of oceanic propagule dispersal have
      often emphasized the role of large-scale factors. We link these two perspectives
      by exploring how propagule dispersal in the ocean is influenced by the "coastal
      boundary layer" (CBL), a region of reduced velocities near the shoreline that
      might substantially modify local-scale dispersal. We used a simple simulation
      model to demonstrate that accounting for the CBL markedly alters transport
      distances, the widths of dispersal distributions, and the fraction of larvae
      retained near their sites of origin (self-retention). Median dispersal distances
      were up to 59% shorter in simulations with a CBL than in those without. Self
      retention of larvae increased by up to 3 orders of magnitude in the presence of
      CBLs, but only minor changes arose in the long-distance tails of the
      distributions, resulting in asymmetric, non-Gaussian kernels analogous to those
      quantified for terrestrial seed dispersal. Because successfully settling larvae
      are commonly those that remain close to shore and interact with the CBL, ignoring
      this pervasive oceanographic feature will substantially alter predictions of
      population self-persistence, estimates of connectivity, and outcomes of
      metapopulation analyses.

PMID- 25616140
TI  - Modeling the influence of genetic and environmental variation on the expression
      of plant life cycles across landscapes.
AB  - Organisms develop through multiple life stages that differ in environmental
      tolerances. The seasonal timing, or phenology, of life-stage transitions
      determines the environmental conditions to which each life stage is exposed and
      the length of time required to complete a generation. Both environmental and
      genetic factors contribute to phenological variation, yet predicting their
      combined effect on life cycles across a geographic range remains a challenge. We
      linked submodels of the plasticity of individual life stages to create an
      integrated model that predicts life-cycle phenology in complex environments. We
      parameterized the model for Arabidopsis thaliana and simulated life cycles in
      four locations. We compared multiple "genotypes" by varying two parameters
      associated with natural genetic variation in phenology: seed dormancy and floral
      repression. The model predicted variation in life cycles across locations that
      qualitatively matches observed natural phenology. Seed dormancy had larger
      effects on life-cycle length than floral repression, and results suggest that a
      genetic cline in dormancy maintains a life-cycle length of 1 year across the
      geographic range of this species. By integrating across life stages, this
      approach demonstrates how genetic variation in one transition can influence
      subsequent transitions and the geographic distribution of life cycles more
      generally.

PMID- 25616141
TI  - Histocompatibility as adaptive response to discriminatory within-organism
      conflict: a historical model.
AB  - Multicellular tissue compatibility, or histocompatibility, restricts fusion to
      close kin. Histocompatibility depends on hypervariable cue genes, which often
      have more than 100 alleles in a population. To explain the evolution of
      histocompatibility, I here take a historical approach. I focus on the specific
      example of marine invertebrate histocompatibility. I use simple game-theoretical
      models to show that histocompatibility can evolve through five steps. These steps
      include the evolution of indiscriminate fusion, the evolution of discriminatory
      within-organism conflict, the evolution of minor histocompatibility, the
      evolution of major histocompatibility, and the evolution of major
      histocompatibility cue polymorphism. Allowing for gradual evolution reveals
      discriminatory within-organism conflict as a selective pressure for
      histocompatibility and associated cue polymorphism. Existing data from marine
      invertebrates and other organisms are consistent with this hypothesis.

PMID- 25616142
TI  - The phenotypic effects of spontaneous mutations in different environments.
AB  - Understanding the context dependence of mutation represents the current frontier
      of mutation research. In particular, understanding how traits vary in their
      abilities to accrue mutational variation and how the environment influences
      expression of mutant phenotypes yields insight into evolutionary processes. We
      conducted phenotypic assays in four environments using a set of Daphnia pulex
      mutation accumulation lines to examine the context dependence of mutation. Life
      history traits accrued mutational variance faster than morphological traits when
      considered in individual environments. Across environments, the mutational
      variance in plasticity was also greater for life-history traits than for
      morphological traits, although this pattern was less robust. In addition, the
      expression of mutational variance depended on the environment, which resulted in
      changes in the rank order of genotype performance across environments in some
      cases. Such cryptic genetic variation resulting from mutation may maintain
      genetic diversity and allow for rapid adaptation in spatially or temporally
      variable environments.

PMID- 25616143
TI  - Noisy neighbors can hamper the evolution of reproductive isolation by reinforcing
      selection.
AB  - Reinforcement is the process by which selection against hybridization leads to an
      increase in reproductive isolation. The influence of reinforcing selection can be
      detected when sympatric individuals (those from areas of secondary contact) show
      a higher degree of prezygotic isolation than allopatric individuals (those from
      areas outside each other's range). In areas of secondary contact with Drosophila
      santomea, Drosophila yakuba females show reinforcement of gametic isolation but
      not behavioral isolation, despite the fact that both behavioral and gametic
      isolation evolve in D. yakuba in experimental sympatry. Using behavioral assays
      and experimental evolution, I studied how both gametic and behavioral isolation
      are affected by biotic factors that the two species encounter in their natural
      environment. I show that if D. yakuba females are in environments where D.
      yakuba, D. santomea, and males from other species coexist, these females cannot
      fully discern between conspecific and heterospecific males. In such complex
      environments, gametic but not behavioral isolation evolves. The presence of
      nonhybridizing species can constrain the effect of reinforcement on behavioral
      isolation.

PMID- 25616144
TI  - The adaptive significance of provisioning and foraging coordination between
      breeding partners.
AB  - Sexual conflict over parental care relies on the fundamental assumption that
      parents do not share the cost of their partner's effort on future reproduction.
      However, this is unlikely to be true whenever partners breed together more than
      once. In that case, individuals should try to optimize the cost and benefits for
      the pair, rather than only for themselves. Here we seek to establish whether the
      synchronization of parents' provisioning visits to the nest could fulfill this
      function. We conducted a brood-size manipulation experiment on wild zebra finches
      to test whether nest visit synchrony was flexible and beneficial for nestlings'
      growth, while controlling for the confounding effects of pair "quality" and
      synchrony away from the nest during foraging. Using a network of readers to track
      parents at nests and feeding stations, we found that nest visit synchrony
      responded directly to the brood manipulation and increased with brood size.
      Synchrony at the nest and while foraging were correlated, but the latter better
      predicted nestling mass, possibly because it was associated with more regular
      provisioning patterns. Our findings suggest that parental coordination could
      indeed play an important role in partners' investment decisions, underpinning the
      evolution of the most prominent mating system in birds.

PMID- 25616145
TI  - Information on biotic interactions improves transferability of distribution
      models.
AB  - Predicting changes in species' distributions is a crucial problem in ecology,
      with leading methods relying on information about species' putative climatic
      requirements. Empirical support for this approach relies on our ability to use
      observations of a species' distribution in one region to predict its range in
      other regions (model transferability). On the basis of this observation,
      ecologists have hypothesized that climate is the strongest determinant of
      species' distributions at large spatial scales. However, it is difficult to
      reconcile this claim with the pervasive effects of biotic interactions. Here, we
      resolve this apparent paradox by demonstrating how biotic interactions can affect
      species' range margins yet still be compatible with model transferability. We
      also identify situations where small changes in species' interactions
      dramatically shift range margins.

PMID- 25616146
TI  - Spore germination determines yeast inbreeding according to fitness in the local
      environment.
AB  - Gene combinations conferring local fitness may be destroyed by mating with
      individuals that are adapted to a different environment. This form of outbreeding
      depression provides an evolutionary incentive for self-fertilization. We show
      that the yeast Saccharomyces paradoxus tends to self-fertilize when it is well
      adapted to its local environment but tends to outcross when it is poorly adapted.
      This behavior could preserve combinations of genes when they are beneficial and
      break them up when they are not, thereby helping adaptation. Haploid spores must
      germinate before mating, and we found that fitter spores had higher rates of
      germination across a 24-hour period, increasing the probability that they mate
      with germinated spores from the same meiotic tetrad. The ability of yeast spores
      to detect local conditions before germinating and mating suggests the novel
      possibility that these gametes directly sense their own adaptation and
      plastically adjust their breeding strategy accordingly.

PMID- 25616147
TI  - Long-term dynamics and hotspots of change in a desert grassland plant community.
AB  - Natural and anthropogenic disturbances are key drivers of vegetation dynamics.
      The hierarchical-response framework proposes that directional change in
      communities is driven by chronic resource alterations resulting from global
      environmental change in the absence of disturbance. Because vegetation is
      spatially heterogeneous, some local areas within a larger community may be more
      dynamic than others. Thus, the average rate of change may mask dynamic hotspots
      and local areas where vegetation remains stable. We used long-term data from two
      line-intercept transects in undisturbed desert grassland to quantify large-scale
      community dynamics, small-scale local dynamics, and boundary dynamics of grass
      patches in the absence of disturbance. We found that directional change in
      species composition was evident but that the overall rate of change varied
      spatially. Cover of both dominant grasses, Bouteloua eriopoda and Bouteloua
      gracilis, increased over the full transects, but most change occurred in
      localized hotspots. Patch boundaries of the dominant grasses exhibited both
      stability and local dynamics. Overall, the increasing abundance of B. eriopoda
      may predispose this grassland to shrub encroachment, whereas locally stable areas
      may prove resistant to state transition. More generally, global environmental
      change may be a pervasive driver of vegetation dynamics through localized
      hotspots of temporal change and spatially varying changes in patch boundaries in
      the absence of disturbance.

PMID- 25616148
TI  - Migraine in young children.

PMID- 25616149
TI  - New generation solar cells: concepts, trends and perspectives.
AB  - Organic, dye-sensitized and perovskite solar cell technologies have triggered
      widespread interest in recent years due to their very promising potential towards
      a high solar electricity future. A number of important milestones have marked the
      roadmap of each sector on the way to today's outstanding performances, but there
      still remains plenty of scope for further improvement. The most influential
      landmarks, together with basic concepts and future perspectives, are unraveled in
      this review. 

PMID- 25616150
TI  - Causes and root causes of a multistate fungal meningitis outbreak.

PMID- 25616151
TI  - An Evidence-Based Systematic Review of Lutein by the Natural Standard Research
      Collaboration.
AB  - ABSTRACT An evidence-based systematic review of lutein by the Natural Standard
      Research Collaboration consolidates the safety and efficacy data available in the
      scientific literature using a validated, reproducible grading rationale. This
      article includes written and statistical analysis of clinical trials, plus a
      compilation of expert opinion, folkloric precedent, history, pharmacology,
      kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

PMID- 25616152
TI  - Features and predictors of activity limitations and participation restriction 2
      years after intensive rehabilitation following first-ever stroke.
AB  - BACKGROUND: Although stroke-related disability has been extensively studied, only
      few studies have investigated Participation restriction in chronic stroke
      survivors. AIM: To identify features and predictors of Activity limitation and
      Participation restriction in the chronic phase of a first-ever stroke. DESIGN:
      Cross-sectional observational study. SETTING: Comprehensive stroke unit with
      outpatient rehabilitation facility. POPULATION: Subjects submitted to intensive
      rehabilitation after first-ever stroke, from 1st January 2009 to 31st December
      2010. METHODS: Participation was investigated through the Frenchay Activity Index
      (FAI) and the Functional Status Questionnaire (FSQ) at 2.4+/-0.5 years after the
      event. Basic activities of daily living (ADL) and mood were also assessed through
      the Modified Barthel Index (MBI) and the Beck Depression Inventory (BDI). A
      retrospective search of the medical records looked for: type/side of brain
      lesion, stroke clinical syndromes, comorbidities and functional condition at
      discharge from intensive rehabilitation (upper limb motricity index-ULMI-,
      Functional Ambulation Category-FAC, MBI, cognitive deficits). RESULTS: Forty-five
      subjects (17 female, age 70.1+/-11.5 years) were enrolled. They showed a striking
      restriction in their Participation, mainly for FAI-outdoor activities (median FAI
      score was <50% of the theoretical maximum). A poor gait function (FAC) and an
      impaired mood (BDI) were the only independent predictors of FAI indoor (F=6.1;
      p=,005; R^2= 64%) and outdoor activities (F=4.1; P=0.01; R^2=48%), respectively.
      The univariate analysis showed a strong dependence of all FSQ scores from global
      disability (MBI), motor function impairment (ULMI and FAC) and cognitive
      deficits. Depression influenced "psychological function" score, whereas gait
      capacity was the only factor significantly associated with the "work performance"
      score. The gait function level, achieved after intensive rehabilitation, was
      extrapolated by the multivariate analysis, as the most powerful independent
      predictor of the chronic activity limitations, as measured by MBI (F=33.8,
      P<0.0001, R2=0.539). CONCLUSION: Gait dysfunction is the main factor of Activity
      limitations and Participation restriction in chronic stroke. Participation is
      restricted by global disability, depression, older age and dementia. More than
      50% variance of Participation measures cannot be explained by the quoted factors.
      CLINICAL REHABILITATION IMPACT: The study results support the need to integrate
      the standard rehabilitation approach with vocational rehabilitation in order to
      reduce Participation restriction.

PMID- 25616154
TI  - Development and validation of a LC-MS assay for the quantification of ikh12 a
      novel anti-tumor candidate in rat plasma and tissues and its application in a
      pharmacokinetic study.
AB  - IKH12 is a novel histone deacetylase 6 selective inhibitor. A rapid and sensitive
      liquid chromatography tandem mass spectrometry method was developed and validated
      for the quantification of IKH12 in rat plasma and tissue with kendine 91 as
      internal standard (IS). The samples were prepared by liquid-liquid extraction
      with tert-butyl methyl ether. The chromatographic separation was accomplished by
      using a Zorbax Extend C18 4.6 * 150 mm, 5 um column, with a mobile phase
      consisting of methanol and 0.1% formic acid (75:25 v/v). Multiple reaction
      monitoring, using electrospray ionization in positive ion mode, was employed to
      quantitatively detect IKH12 and IS. The monitored transitions were set at m/z 418
      -> 252 and 444 -> 169 for IKH12 and kendine 91, respectively. The calibration
      curve was linear over the concentration range 2-1000 ng mL(-1) . The intra- and
      inter-assay precision and accuracy of the quality controls and the limit of
      quantification were satisfactory in all cases (according to European Medicines
      Agency guidelines). Stability studies showed that plasma samples were stable in
      the chromatography rack for 24 h and at -80 degrees C for 2 months and also after
      three freeze-thaw cycles. This method was successfully applied to a
      pharmacokinetic study of IKH12 in rat.

PMID- 25616153
TI  - Markers of inflammation and coagulation after long-term exposure to coarse
      particulate matter: a cross-sectional analysis from the multi-ethnic study of
      atherosclerosis.
AB  - BACKGROUND: Toxicological research suggests that coarse particles (PM10-2.5) are
      inflammatory, but responses are complex and may be best summarized by multiple
      inflammatory markers. Few human studies have investigated associations with PM10
      2.5 and, of those, none have explored long-term exposures. Here we examine long
      term associations with inflammation and coagulation in the Multi-Ethnic Study of
      Atherosclerosis. METHODS: Participants included 3,295 adults (45-84 years of age)
      from three metropolitan areas. Site-specific spatial models were used to estimate
      5-year concentrations of PM10-2.5 mass and copper, zinc, phosphorus, silicon, and
      endotoxin found in PM10-2.5. Outcomes included interleukin-6, C-reactive protein,
      fibrinogen, total homocysteine, D-dimer, factor VIII, plasmin-antiplasmin
      complex, and inflammation and coagulation scores. We used multivariable
      regression with multiply imputed data to estimate associations while controlling
      for potential confounders, including co-pollutants such as fine particulate
      matter. RESULTS: Some limited evidence was found of relationships between
      inflammation and coagulation and PM10-2.5. Endotoxin was the PM10-2.5 component
      most strongly associated with inflammation, with an interquartile range (IQR)
      increase (0.08 EU/m3) associated with 0.15 (95% CI: 0.01, 0.28; p = 0.03) and
      0.08 (95% CI: -0.07, 0.23; p = 0.28) higher inflammation scores before and after
      control for city, respectively. Copper was the component with the strongest
      association with coagulation, with a 4-ng/m3 increase associated with 0.19 (95%
      CI: 0.08, 0.30; p = 0.0008) and 0.12 (95% CI: -0.05, 0.30; p = 0.16) unit higher
      coagulation scores before and after city adjustment, respectively. CONCLUSIONS:
      Our cross-sectional analysis provided some evidence that long-term PM10-2.5
      exposure was associated with inflammation and coagulation, but associations were
      modest and depended on particle composition.

PMID- 25616155
TI  - Comparison of sedentary behaviours among rural men working in offices and on
      farms.
AB  - OBJECTIVE: The aim of this study was to compare objectively measured sedentary
      behaviours among rural Australian men working in desk-based offices and on farms
      during work hours and across the total day. DESIGN: Cross-sectional
      observational. SETTING: The Riverland, South Australia. PARTICIPANTS:
      Participants in this study include 29 farmers and 29 office workers (age 30-65
      years). MAIN OUTCOME MEASURES: Objectively measured sedentary time (number and
      length of sedentary bouts) and steps taken, at work and across the total day.
      RESULTS: During work time, office workers were significantly more sedentary than
      farmers (6.6 +/- 1.5 hours (mean +/- SD) versus 4.3 +/- 1.5 hours, P < 0.05),
      while breaks in sedentary behaviour among office workers were less frequent (45
      +/- 17 versus 49 +/- 17 per day, P < 0.05) and briefer (4.7 +/- 6.8 min versus
      9.7 +/- 6.8 min, P < 0.05). Across the total day, office workers were more
      sedentary than farmers (10.0 +/- 1.6 hours versus 8.1 +/- 1.6 hours, P < 0.05).
      Office workers took fewer steps at work (427 +/- 282 versus 882 +/- 282 steps
      hour(-1) , P < 0.05) and across the whole day (8602 +/- 3486 versus 11 579 +/-
      3486 steps day(-1) , P < 0.05) than farmers. CONCLUSION: In this study, farmers
      were less sedentary than rural men of similar age who work in offices. Further
      research is needed to identify reasons for the particularly high prevalence of
      chronic disease in Australian farmers.

PMID- 25616157
TI  - A novel optical ozone sensor based on purely organic phosphor.
AB  - An optical ozone sensor was developed based on the finding that a purely organic
      phosphor linearly loses its phosphorescence emission intensity in the presence of
      varying concentration of ozone gas and ozonated water. Compared to conventional
      conductance-based inorganic sensors, our novel sensory film has many advantages
      such as easy fabrication, low-cost, and portability. NMR data confirmed that
      phosphorescence drop is attributed to oxidation of the core triplet generating
      aldehyde group of the phosphor. We observed that linear correlation between
      phosphorescence and ozone concentration and it can detect ozone concentrations of
      0.1 ppm that is the threshold concentration harmful to human tissue and
      respiratory organs. Like a litmus paper, this ozone sensor can be fabricated as a
      free-standing and disposable film. 

PMID- 25616156
TI  - Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune
      mediated hepatitis in mice in a CD40-dependent manner.
AB  - Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs)
      accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in
      two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB
      mice with Concanavalin A (Con A) or alpha-galactosylceramide resulted in
      increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs
      into naive mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+)
      cells revealed a polarized proinflammatory gene signature after Con A treatment.
      An IFN-gamma-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells
      along with an upregulation of CD80, CD86, and CD1d after Con A treatment was
      observed. Con A treatment resulted in a loss of suppressor function by tumor
      induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)
      mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased
      arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally,
      blockade of arginase activity in Cd40(-/-) tumor-induced myeloid cells resulted
      in exacerbation of hepatitis and increased ROS production in vivo. Our findings
      indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as
      proinflammatory immune effector cells capable of killing hepatocytes in a CD40
      dependent manner. 

PMID- 25616158
TI  - Genomic discoveries in adult astrocytoma.
AB  - Astrocytomas are the most common glial tumor of the central nervous system.
      Within this category, glioblastoma is the most prevalent and malignant primary
      brain tumor. Glioblastoma can arise de novo, or through progression from lower
      grade lesions, but is uniformly associated with poor outcomes despite surgical
      resection, chemotherapy, and radiation therapy. Recent genomic discoveries have
      provided new insight into gliomagenesis and have identified key genetic
      alterations that have diagnostic, prognostic and predictive capacity. Numerous
      molecular classification schemes have been proposed to sort tumors into
      clinically meaningful categories to guide treatment. However, creating therapy
      targeted towards these alterations has been made challenging by the redundancy of
      essential signal transduction pathways affected in these tumors, intratumoral
      heterogeneity, and the hypermutated profiles of recurrent tumors. Future
      treatment strategies will require a personalized approach with consideration of
      the unique genetic profile of a specific tumor and the use of multimodality
      therapies.

PMID- 25616160
TI  - Breaching the skin barrier through temperature modulations.
AB  - The impermeability of the stratum corneum often hinders the transport of
      molecules across the skin. Temperature modulations in the skin and the
      application of local heat both have the potential of circumventing this problem
      temporarily and reversibly and when applied, may aid in enhancing drug diffusion
      through the skin. A controlled and precise application of heat has the ability to
      create a cascade of events in the skin and thus aids in facilitating a faster
      movement of molecules into and across the skin. Possible mechanisms of enhancing
      drug permeation include: a) increase in drug diffusivity in the vehicle and/or in
      the skin, b) increase in partitioning and diffusion, c) disturbance in the lipid
      structure of the stratum corneum, and d) increased local blood flow. These
      mechanisms may operate individually or concurrently. The creation of micropores
      or channels in response to exposure to very high heat energy for a fraction of
      time is another technique that can facilitate the transport, known as thermal
      ablation. These micropores then serve as channels from where drug molecules can
      escape from formulations into the skin at a much faster rate than through passive
      diffusion. This review, therefore, summarises the effects that temperature
      modulations may have on the permeability of the skin. Physical techniques of heat
      induced skin ablation, such as chemical heating, thermoporation, radiofrequency
      induced thermal ablation, and laser induced thermal ablation are also presented
      in this review. 

PMID- 25616159
TI  - ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic
      children and young adults.
AB  - BACKGROUND: The clinical response to inhaled corticosteroids (ICS) is associated
      with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to
      relate variations in genes in the steroid pathway and asthma susceptibility genes
      to exacerbations in children and young adults treated with ICS. METHODS: We
      performed a meta-analysis of three cohort studies: Pharmacogenetics of Asthma
      Medication in Children: Medication with Anti-Inflammatory effects (n = 357, age:
      4-12 years, the Netherlands), BREATHE (n = 820, age: 3-22 years, UK) and
      Paediatric Asthma Gene Environment Study (n = 391, age: 2-16 years, UK).
      Seventeen genes were selected based on a role in the glucocorticoid signalling
      pathway or a reported association with asthma. Two outcome parameters were used
      to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in
      the previous year. The most significant associations were tested in three
      independent validation cohorts; the Childhood Asthma Management Programme
      (clinical trial, n = 172, age: 5-12 years, USA), the Genes- environment and
      Mixture in Latino Americans II- study (n = 745, age: 8-21, USA) and the
      Pharmacogenetics of adrenal suppression cohort (n = 391, age: 5-18, UK) to test
      the robustness of the findings. Finally, all results were meta-analysed. RESULTS:
      Two SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were
      associated at a nominal level with an increased risk of exacerbations in
      asthmatics using ICS in the three cohorts studied. In a meta-analysis of all six
      studies, ST13 rs138335 remained associated with an increased risk of asthma
      related hospital visits and OCS use in the previous year; OR = 1.22 (P = 0.013)
      and OR = 1.22 (P = 0.0017), respectively. CONCLUSION AND CLINICAL RELEVANCE: A
      novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid
      receptor, is associated with exacerbations in asthmatic children and young adults
      despite their ICS use. Genetic variation in the glucocorticoid signalling pathway
      may contribute to the interindividual variability in clinical response to ICS
      treatment in children and young adults.

PMID- 25616161
TI  - RPM peptide conjugated bioreducible polyethylenimine targeting invasive colon
      cancer.
AB  - CPIEDRPMC (RPM) peptide is a peptide that specifically targets invasive
      colorectal cancer, which is one of the leading causes of cancer-related deaths
      worldwide. In this study, we exploited RPM peptide as a targeting ligand to
      produce a novel and efficient gene delivery system that could potentially be used
      to treat invasive colon cancer. In order to achieve enhanced specificity to colon
      cancer cells, the RPM peptide was conjugated to a bioreducible gene carrier
      consisting of a reducible moiety of disulfide-crosslinked low molecular weight
      polyethylenimine, IR820 dye, and polyethylene glycol. Here, we examined the
      physiochemical properties, cytotoxicity, in vitro transfection efficiency, and in
      vivo biodistribution of the RPM-conjugated polyplex. Our results showed that the
      RPM-conjugated gene carrier formed a compact polyplex with pDNA that had low
      toxicity. Furthermore, the RPM-conjugated polymer not only had higher cellular
      uptake in invasive colon cancer than the non-targeted polymer, but also showed
      enhanced transfection efficiency in invasive colon cancer cells in vitro and in
      vivo. 

PMID- 25616163
TI  - Evaluation and comparison of benchmark QSAR models to predict a relevant REACH
      endpoint: The bioconcentration factor (BCF).
AB  - The bioconcentration factor (BCF) is an important bioaccumulation hazard
      assessment metric in many regulatory contexts. Its assessment is required by the
      REACH regulation (Registration, Evaluation, Authorization and Restriction of
      Chemicals) and by CLP (Classification, Labeling and Packaging). We challenged
      nine well-known and widely used BCF QSAR models against 851 compounds stored in
      an ad-hoc created database. The goodness of the regression analysis was assessed
      by considering the determination coefficient (R(2)) and the Root Mean Square
      Error (RMSE); Cooper's statistics and Matthew's Correlation Coefficient (MCC)
      were calculated for all the thresholds relevant for regulatory purposes (i.e.
      100L/kg for Chemical Safety Assessment; 500L/kg for Classification and Labeling;
      2000 and 5000L/kg for Persistent, Bioaccumulative and Toxic (PBT) and very
      Persistent, very Bioaccumulative (vPvB) assessment) to assess the classification,
      with particular attention to the models' ability to control the occurrence of
      false negatives. As a first step, statistical analysis was performed for the
      predictions of the entire dataset; R(2)>0.70 was obtained using CORAL, T.E.S.T.
      and EPISuite Arnot-Gobas models. As classifiers, ACD and logP-based equations
      were the best in terms of sensitivity, ranging from 0.75 to 0.94. External
      compound predictions were carried out for the models that had their own training
      sets. CORAL model returned the best performance (R(2)ext=0.59), followed by the
      EPISuite Meylan model (R(2)ext=0.58). The latter gave also the highest
      sensitivity on external compounds with values from 0.55 to 0.85, depending on the
      thresholds. Statistics were also compiled for compounds falling into the models
      Applicability Domain (AD), giving better performances. In this respect, VEGA
      CAESAR was the best model in terms of regression (R(2)=0.94) and classification
      (average sensitivity>0.80). This model also showed the best regression
      (R(2)=0.85) and sensitivity (average>0.70) for new compounds in the AD but not
      present in the training set. However, no single optimal model exists and, thus,
      it would be wise a case-by-case assessment. Yet, integrating the wealth of
      information from multiple models remains the winner approach. 

PMID- 25616164
TI  - Generating allergen-specific human IgEs for immunoassays by employing human
      epsilon gene knockin mice.
AB  - BACKGROUND: Antigen-specific human IgEs are important reagents in immunoassays to
      quantify antigen-specific IgEs in allergic patients, but they are not easy to
      prepare. METHODS: We constructed a knockin homozygous mouse strain, referred to
      as HepsilonkappaKI strain, whose gene segment encoding gamma1 constant region has
      been replaced by that encoding human epsilon constant region and gene segment
      encoding kappa constant region replaced by that encoding human kappa constant
      region. The mice were tested for their ability to produce antigen-specific
      chimeric human IgE (with mouse variable regions) upon the immunization with
      ovalbumin and papain. Subsequently, the spleen cells from the immunized mice were
      used as the source of B cells for the preparation of hybridomas, which secreted
      monoclonal human IgE antibodies specific for the antigens. RESULTS: The
      HepsilonkappaKI mice expressed human IgE (epsilon, kappa) in serum at levels 10-
      to 30-fold higher than those of mouse IgE. Upon immunization with an antigen, the
      mice yielded splenic B cells for preparing hybridomas that secrete chimeric human
      IgE specific for the antigen. Purified IgEs from those hybridomas could activate
      a basophilic cell line to undergo degranulation upon the stimulation with their
      respective antigens. CONCLUSIONS: We have developed a human epsilon gene and
      kappa gene knockin mouse strain, which is useful for producing various antigen
      specific chimeric human IgEs for potential use as standards in immunoassays.

PMID- 25616165
TI  - Solid-state circularly polarised luminescence of atropisomeric fluorophores
      embedded in achiral myo-inositol-containing polyurethanes.
AB  - We investigated the ground- and photoexcited-state chiralities of two chiral
      fluorophores with a rigid framework embedded in two achiral polyurethanes as the
      solid matrices. As the fluorophores, we used two pairs of atropisomeric
      binaphthyl derivatives, (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate [(R)
      1a] and (R)-(-)-(3,5-dioxa-4-phosphacyclohepta-[2,1-a:3,4-a']dinaphthalen-4-yl)
      dimethylamine [(R)-1b], and for comparison, their optical antipodes (S)-1a and
      (S)-1b. As the solid matrices, we used two soluble achiral polyurethanes (2a and
      2b) derived from the naturally occurring myo-inositol as the building block,
      because these polymers had a high glass transition temperature of ~150  degrees
      C. The chiral fluorophores in the polyurethanes emitted circularly polarised
      luminescence with a high circular anisotropy of ~0.6-1.5 * 10(-3). Regardless of
      the matrix, (R)- and (S)-1a had nearly mirror-image chiroptical properties in the
      ground and photoexcited states, as did (R)- and (S)-1b.

PMID- 25616162
TI  - GSK3beta-activation is a point of convergence for HIV-1 and opiate-mediated
      interactive neurotoxicity.
AB  - Infection of the CNS with HIV-1 occurs rapidly after primary peripheral
      infection. HIV-1 can induce a wide range of neurological deficits, collectively
      known as HIV-1-associated neurocognitive disorders. Our previous work has shown
      that the selected neurotoxic effects induced by individual viral proteins, Tat
      and gp120, and by HIV(+) supernatant are enhanced by co-exposure to morphine.
      This mimics co-morbid neurological effects observed in opiate-abusing HIV(+)
      patients. Although there is a correlation between opiate drug abuse and
      progression of HIV-1-associated neurocognitive disorders, the mechanisms
      underlying interactions between HIV-1 and opiates remain obscure. Previous
      studies have shown that HIV-1 induces neurotoxic effects through abnormal
      activation of GSK3beta. Interestingly, expression of GSK3beta has shown to be
      elevated in brains of young opiate abusers indicating that GSK3beta is also
      linked to neuropathology seen with opiate-abusing patients. Thus, we hypothesize
      that GSK3beta activation is a point of convergence for HIV- and opiate-mediated
      interactive neurotoxic effects. Neuronal cultures were treated with supernatant
      from HIV-1SF162-infected THP-1 cells, in the presence or absence of morphine and
      GSK3beta inhibitors. Our results show that GSK3beta inhibitors, including
      valproate and small molecule inhibitors, significantly reduce HIV-1-mediated
      neurotoxic outcomes, and also negate interactions with morphine that result in
      cell death, suggesting that GSK3beta-activation is an important point of
      convergence and a potential therapeutic target for HIV- and opiate-mediated
      neurocognitive deficits. 

PMID- 25616166
TI  - Health-related quality of life in children with perceived and diagnosed food
      hypersensitivity.
AB  - BACKGROUND: The few studies measuring health-related quality of life (HRQL) in
      food hypersensitivity (FHS) have found significantly reduced HRQL in patients and
      their families, particularly in the areas of family and social activities,
      emotional issues and family economy. One aspect that has not been studied is the
      effect of suspected FHS (food allergy/intolerance) vs. diagnosed FHS [based on a
      food challenge or a positive skin prick test (SPT) and good clinical history] on
      HRQL. Therefore, the aim of this study was to investigate the HRQL in children
      with a proven diagnosis of FHS vs. those with reported FHS. METHODS: We have
      utilized the 10-yr old follow-up cohort of the Food Allergy and Intolerance
      Research (FAIR) study from the Isle of Wight and assessed the child's HRQL with
      the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) which
      measures HRQL using four domains: food anxiety, emotional impact, social and
      dietary limitation. RESULTS: When comparing the two groups of children (proven
      FHS vs. perceived FHS), no difference in HRQL was found, although food anxiety
      showed a p-value of (p = 0.062). This was also the case when correcting for all
      confounding factors identified. CONCLUSION: We have found that having a clear
      diagnosis of FHS is not an independent predictor of HRQL. Future studies are
      required comparing two more similar groups. We also need to focus more on the
      effect of continuous input from the multidisciplinary team on HRQL and which
      particular factors of FHS management affect HRQL.

PMID- 25616167
TI  - Small vessels and long lesions: changing label indications for drug eluting
      stents.

PMID- 25616168
TI  - 38 mm Stents: go big and go long.

PMID- 25616169
TI  - At a crossroads: an Amulet in the uneasy left atrial appendage crown.

PMID- 25616170
TI  - Left atrial appendage closure-facing the truth and forging the future.

PMID- 25616171
TI  - Evaluation of industrial Saccharomyces cerevisiae strains as the chassis cell for
      second-generation bioethanol production.
AB  - To develop a suitable Saccharomyces cerevisiae industrial strain as a chassis
      cell for ethanol production using lignocellulosic materials, 32 wild-type strains
      were evaluated for their glucose fermenting ability, their tolerance to the
      stresses they might encounter in lignocellulosic hydrolysate fermentation and
      their genetic background for pentose metabolism. The strain BSIF, isolated from
      tropical fruit in Thailand, was selected out of the distinctly different strains
      studied for its promising characteristics. The maximal specific growth rate of
      BSIF was as high as 0.65 h(-1) in yeast extract peptone dextrose medium, and the
      ethanol yield was 0.45 g g(-1) consumed glucose. Furthermore, compared with other
      strains, this strain exhibited superior tolerance to high temperature,
      hyperosmotic stress and oxidative stress; better growth performance in
      lignocellulosic hydrolysate; and better xylose utilization capacity when an
      initial xylose metabolic pathway was introduced. All of these results indicate
      that this strain is an excellent chassis strain for lignocellulosic ethanol
      production.

PMID- 25616172
TI  - Manganese rescues adverse effects on lifespan and development in Podospora
      anserina challenged by excess hydrogen peroxide.
AB  - For biological systems, balancing cellular levels of reactive oxygen species
      (ROS) is of great importance because ROS are both, essential for cellular
      signaling and dangerous in causing molecular damage. Cellular ROS abundance is
      controlled by a delicate network of molecular pathways. Within this network,
      superoxide dismutases (SODs) are active in disproportion of the superoxide anion
      leading to the formation of hydrogen peroxide. The fungal aging model Podospora
      anserina encodes at least three SODs. One of these is the mitochondrial PaSOD3
      isoform containing manganese as a cofactor. Previous work resulted in the
      selection of strains in which PaSod3 is strongly overexpressed. These strains
      display impairments in growth and lifespan. A computational model suggests a
      series of events to occur in Sod3 overexpressing strains leading to adverse
      effects due to elevated hydrogen peroxide levels. In an attempt to validate this
      model and to obtain more detailed information about the cellular responses
      involved in ROS balancing, we further investigated the PaSod3 overexpressing
      strains. Here we show that hydrogen peroxide levels are indeed strongly increased
      in the mutant strain. Surprisingly, this phenotype can be rescued by the addition
      of manganese to the growth medium. Strikingly, while we obtained no evidence for
      an antioxidant effect of manganese, we found that the metal is required for
      induction of components of the ROS scavenging network and lowers the hydrogen
      peroxide level of the mutant. A similar effect of manganese on lifespan reversion
      was obtained in wild-type strains challenged with exogenous hydrogen peroxide. It
      appears that manganese is limited under high hydrogen peroxide and suggests that
      a manganese-dependent activity leads to the induction of ROS scavenging
      components. 

PMID- 25616173
TI  - Chronological analysis of caloric restriction-induced alteration of fatty acid
      biosynthesis in white adipose tissue of rats.
AB  - The beneficial actions of caloric restriction (CR) could be mediated in part by
      metabolic remodeling of white adipose tissue (WAT). Recently, we suggested that
      CR for 6 months increased the expressions of proteins involved in de novo fatty
      acid (FA) biosynthesis in WAT of 9-month-old rats. Herein, we compared the CR
      induced chronological alterations of the expression of mRNAs and/or proteins
      involved in FA biosynthesis in the WAT and liver of rats subjected to CR starting
      from 3 months of age and their age-matched controls fed ad libitum. The findings
      suggested that CR was more effective on FA biosynthesis in WAT than in liver. In
      WAT, CR markedly increased the expressions of mRNAs and/or proteins involved in
      FA biosynthesis, including sterol regulatory element-binding protein 1c
      (SREBP1c), a master transcriptional regulator of FA biosynthesis, throughout the
      experimental period. Interestingly, the CR-enhanced upregulation was temporally
      attenuated at 5 months of age. CR markedly increased the nuclear phosphorylated
      form of Akt only at 3.5 months of age. In contrast, CR significantly reduced the
      expression of leptin at 9 months of age. The CR-induced upregulation was not
      observed in obese fa/fa Zucker rats homozygous for nonfunctional leptin receptor.
      Collectively, these data indicate that the V-shaped chronological alterations in
      WAT are regulated via SREBP1c, which is probably activated by CR duration
      dependent modulation of both insulin and leptin signaling.

PMID- 25616175
TI  - CASSIA--a dynamic model for predicting intra-annual sink demand and interannual
      growth variation in Scots pine.
AB  - The control of tree growth vs environment by carbon sources or sinks remains
      unresolved although it is widely studied. This study investigates growth of tree
      components and carbon sink-source dynamics at different temporal scales. We
      constructed a dynamic growth model 'carbon allocation sink source interaction'
      (CASSIA) that calculates tree-level carbon balance from photosynthesis,
      respiration, phenology and temperature-driven potential structural growth of tree
      organs and dynamics of stored nonstructural carbon (NSC) and their modifying
      influence on growth. With the model, we tested hypotheses that sink demand
      explains the intra-annual growth dynamics of the meristems, and that the source
      supply is further needed to explain year-to-year growth variation. The predicted
      intra-annual dimensional growth of shoots and needles and the number of cells in
      xylogenesis phases corresponded with measurements, whereas NSC hardly limited the
      growth, supporting the first hypothesis. Delayed GPP influence on potential
      growth was necessary for simulating the yearly growth variation, indicating also
      at least an indirect source limitation. CASSIA combines seasonal growth and
      carbon balance dynamics with long-term source dynamics affecting growth and thus
      provides a first step to understanding the complex processes regulating intra-
      and interannual growth and sink-source dynamics. 

PMID- 25616174
TI  - Fornical and nonfornical projections from the rat hippocampal formation to the
      anterior thalamic nuclei.
AB  - The hippocampal formation and anterior thalamic nuclei form part of an
      interconnected network thought to support memory. A central pathway in this
      mnemonic network comprises the direct projections from the hippocampal formation
      to the anterior thalamic nuclei, projections that, in the primate brain,
      originate in the subicular cortices to reach the anterior thalamic nuclei by way
      of the fornix. In the rat brain, additional pathways involving the internal
      capsule have been described, linking the dorsal subiculum to the anteromedial
      thalamic nucleus, as well as the postsubiculum to the anterodorsal thalamic
      nucleus. Confirming such pathways is essential in order to appreciate how
      information is transferred from the hippocampal formation to the anterior
      thalamus and how it may be disrupted by fornix pathology. Accordingly, in the
      present study, pathway tracers were injected into the anterior thalamic nuclei
      and the dorsal subiculum of rats with fornix lesions. Contrary to previous
      descriptions, projections from the subiculum to the anteromedial thalamic nucleus
      overwhelmingly relied on the fornix. Dorsal subiculum projections to the majority
      of the anteroventral nucleus also predominantly relied on the fornix, although
      postsubicular inputs to the lateral dorsal part of the anteroventral nucleus, as
      well as to the anterodorsal and laterodorsal thalamic nuclei, largely involved a
      nonfornical pathway, via the internal capsule.

PMID- 25616177
TI  - Multimodality guidance for accurate bronchoscopic insertion of fiducial markers.
AB  - INTRODUCTION: Fiducial markers act as visible surrogates of tumor position during
      image-guided radiotherapy. Marker placement has been attempted percutaneously but
      is associated with high rates of pneumothorax and chest drain placement. METHODS:
      Patients undergoing radical radiation treatment for non-small-cell lung cancer
      underwent bronchoscopic implantation of gold fiducials using radial probe
      endobronchial ultrasound (EBUS) with virtual bronchoscopy and fluoroscopic
      guidance to achieve tumor localization and placement within/adjacent to
      peripheral lung tumors. For tumors not localized using radial EBUS, fiducial
      placement was achieved by electromagnetic navigation to the vicinity of the
      tumor. RESULTS: Eighteen fiducials were placed to mark 16 lesions in 15 patients.
      In nine patients (60%), fiducials were implanted at the time of diagnostic
      bronchoscopy. No procedural complications occurred. EBUS localization allowed
      marker implantation within the target lesion in 12 cases. In four lesions,
      electromagnetic navigation bronchoscopy-guided implantation achieved a median
      fiducial-lesion distance of 6 mm (mean 12 mm). No marker migration occurred after
      the implantation of two-band markers; however, early migration was observed in
      two of eight (25%) of the smaller linear fiducials. No migration during the
      course of radiation therapy was observed. CONCLUSION: Fiducial marker placement
      is easily and safely performed bronchoscopically, including at the time of
      diagnostic bronchoscopy. Marker geometry appears important in stability of
      bronchoscopically inserted fiducials. Future studies are required to confirm the
      optimal marker size, geometry, and spatial relationship with the target lesion.

PMID- 25616178
TI  - The impact of thymoma histotype on prognosis in a worldwide database.
AB  - INTRODUCTION: The rarity of thymomas and lack of multi-institutional studies have
      hampered therapeutic progress for decades. To overcome this, the members of the
      International Thymic Malignancy Interest Group created a worldwide retrospective
      database. This database was analyzed regarding the demographic and geographic
      distribution of thymomas and the impact of different variables on survival and
      recurrence. METHODS: This study analyzed 4221 thymomas diagnosed between 1983 and
      2012 with World Health Organization histotype information from the International
      Thymic Malignancy Interest Group database. Associations to survival and
      recurrence were studied by univariate and multivariate analyses. RESULTS: Type B2
      thymoma is the most common (28%) and type A the least common (12%) histotypes.
      They are significantly more frequent in Europe and the United States than Asia.
      Type A and AB occur at significantly higher age than other thymomas (64 and 57
      years, respectively). There are no differences in gender distribution. Stage is
      lower in type A (90% in stages I-II) and AB than B1 to B3 thymomas (38% of type
      B3 in stage III). In univariate analysis, recurrence is significantly less
      frequent among stage I/II tumors, in type A and AB (recurrence rates, 1-2%) than
      B1 to B3 thymomas (2-7%). Multivariate analysis reveals an impact of age, stage,
      and resection status on survival and recurrence, whereas for histology there is
      only a significant impact on recurrence. CONCLUSION: New findings are (1)
      geographic differences such as a lower incidence of type A and B2 thymoma in
      Asia; and (2) impact of stage and histology, the latter partially limited to
      early stage disease, on recurrence.

PMID- 25616179
TI  - The maternal deprivation animal model revisited.
AB  - Early life stress, in the form of MD (24h at pnd 9), interferes with brain
      developmental trajectories modifying both behavioral and neurobiochemical
      parameters. MD has been reported to enhance neuroendocrine responses to stress,
      to affect emotional behavior and to impair cognitive function. More recently,
      changes in body weight gain, metabolic parameters and immunological responding
      have also been described. Present data give support to the fact that neuronal
      degeneration and/or astrocyte proliferation are present in specific brain
      regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are
      particularly vulnerable to the effects of neonatal stress. The MD animal model
      arises as a valuable tool for the investigation of the brain processes occurring
      at the narrow time window comprised between pnd 9 and 10 that are critical for
      the establishment of brain circuitries critical for the regulation of behavior,
      metabolism and energy homeostasis. In the present review we will discuss three
      possible mechanisms that might be crucial for the effects of MD, namely, the
      rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the
      enhanced endocannabinoid signaling during the specific critical period of MD. A
      better understanding of the mechanisms underlying the detrimental consequences of
      MD is a concern for public health and may provide new insights into mental health
      prevention strategies and into novel therapeutic approaches in neuropsychiatry. 

PMID- 25616180
TI  - The neurobiology of thalamic amnesia: Contributions of medial thalamus and
      prefrontal cortex to delayed conditional discrimination.
AB  - Although medial thalamus is well established as a site of pathology associated
      with global amnesia, there is uncertainty about which structures are critical and
      how they affect memory function. Evidence from human and animal research suggests
      that damage to the mammillothalamic tract and the anterior, mediodorsal (MD),
      midline (M), and intralaminar (IL) nuclei contribute to different signs of
      thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei,
      structures identified in animal studies as critical nodes in prefrontal cortex
      (PFC)-related pathways that are necessary for delayed conditional discrimination.
      Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to
      position (DNMTP) task revealed discrete populations encoding information related
      to planning, execution, and outcome of DNMTP-related actions and delay-related
      activity signaling previous reinforcement. Parallel studies recording the
      activity of MD and IL neurons and examining the effects of unilateral thalamic
      inactivation on the responses of PFC neurons demonstrated a close coupling of
      central thalamic and PFC neurons responding to diverse aspects of DNMTP and
      provide evidence that thalamus interacts with PFC neurons to give rise to complex
      goal-directed behavior exemplified by the DNMTP task. 

PMID- 25616181
TI  - Closing the translational gap between mutant mouse models and the clinical
      reality of psychotic illness.
AB  - As animal models of psychotic illness become more refined, mutant mouse models
      have become increasingly prominent through their ability to inform on the
      structural, cellular and behavioural roles of genes associated with risk for
      psychosis via the phenotypic consequences of disruption of those genes. This
      review will consider recent advances in the field whereby mutant mouse models
      seek to reflect increasing knowledge of psychotic illness, focusing on four main
      themes. Firstly, recent GWAS and rare variant analyses have identified that
      disease-associated targets have not been previously implicated, thereby
      representing novel biological pathways in the illness, and this has implications
      for the modelling field. Secondly, the psychosis is disrespectful to conventional
      diagnostic boundaries, both clinically and in terms of pathobiology: it extends
      beyond schizophrenia to include several diagnostic categories and may be best
      captured in terms of psychopathological dimensions rather than/additional to such
      categories. Thirdly, a given risk gene (G) does not operate in isolation but,
      rather, appears to participate in complex interactions with environmental (E)
      risk factors, i.e., G*E interactions. Lastly, a given risk gene is likely to
      participate in complex, epistatic interactions with other risk genes, i.e., G*G
      interactions. Such studies constitute important steps in closing the
      translational gap between mutant mouse models and the clinical reality of
      psychotic illness.

PMID- 25616183
TI  - The role of the thalamus in schizophrenia from a neuroimaging perspective.
AB  - The thalamus is a crucial node for brain physiology and part of functional and
      structural pathways relevant for schizophrenia. Relatively few imaging studies on
      schizophrenia have focused on this brain region, yet extant evidence supports the
      association between this brain disorder and thalamic anomalies. Nevertheless, the
      mechanisms underlying this association remain largely conjectural. Here, we
      review imaging literature on the relationship between the thalamus and
      schizophrenia, focusing on critical challenges for future studies, in particular:
      (i) the anatomical and functional organization of the thalamus in separate
      nuclei, which are also differently connected with the cortex; (ii) state
      dependent variables, which do not allow firm conclusions on the relevance of
      thalamic correlates as core phenotypes of schizophrenia and (iii) genetic
      variation, which affects thalamic physiology and may lead to variability of
      structural and functional patterns. Current evidence from the studies reviewed
      does not appear conclusive, although the relevance of thalamo-prefrontal
      interactions clearly emerges. Results from imaging genetics are beginning to cast
      insight on possible mechanisms of the involvement of the thalamus in
      schizophrenia. 

PMID- 25616184
TI  - The cognitive thalamus: A bridal chamber not to forget.

PMID- 25616186
TI  - Neurofeedback and its possible relevance for the treatment of Tourette syndrome.
AB  - Neurofeedback is an increasingly recognized therapeutic option in various
      neuropsychiatric disorders to treat dysfunctions in cognitive control as well as
      disorder-specific symptoms. In this review we propose that neurofeedback may also
      reflect a valuable therapeutic option to treat executive control functions in
      Gilles-de-la-Tourette syndrome (GTS). Deficits in executive control functions
      when ADHD symptoms appear in GTS likely reflect pathophysiological processes in
      cortico-thalamic-striatal circuits and may also underlie the motor symptoms in
      GTS. Such executive control deficits evident in comorbid GTS/ADHD depend on
      neurophysiological processes well-known to be modifiable by neurofeedback.
      However, so far efforts to use neurofeedback to treat cognitive dysfunctions are
      scarce. We outline why neurofeedback should be considered a promising treatment
      option, what forms of neurofeedback may prove to be most effective and how
      neurofeedback may be implemented in existing intervention strategies to treat
      comorbid GTS/ADHD and associated dysfunctions in cognitive control. As cognitive
      control deficits in GTS mostly appear in comorbid GTS/ADHD, neurofeedback may be
      most useful in this frequent combination of disorders. 

PMID- 25616182
TI  - Limbic circuitry of the midline thalamus.
AB  - The thalamus was subdivided into three major groups: sensorimotor nuclei (or
      principal/relay nuclei), limbic nuclei and nuclei bridging these two domains.
      Limbic nuclei of thalamus (or 'limbic thalamus') consist of the anterior nuclei,
      midline nuclei, medial division of the mediodorsal nucleus (MDm) and central
      medial nucleus (CM) of the intralaminar complex. The midline nuclei include the
      paraventricular (PV) and paratenial (PT) nuclei, dorsally, and the reuniens (RE)
      and rhomboid (RH) nuclei, ventrally. The 'limbic' thalamic nuclei predominantly
      connect with limbic-related structures and serve a direct role in limbic
      associated functions. Regarding the midline nuclei, RE/RH mainly target limbic
      cortical structures, particularly the hippocampus and the medial prefrontal
      cortex. Accordingly, RE/RH participate in functions involving interactions of the
      HF and mPFC. By contrast, PV/PT mainly project to limbic subcortical structures,
      particularly the amygdala and nucleus accumbens, and hence are critically
      involved in affective behaviors such as stress/anxiety, feeding behavior, and
      drug seeking activities. The anatomical/functional characteristics of MDm and CM
      are very similar to those of the midline nuclei and hence the collection of
      nuclei extending dorsoventrally along the midline/paramidline of the thalamus
      constitute the core of the 'limbic thalamus'. 

PMID- 25616185
TI  - Emotional sensitivity, emotion regulation and impulsivity in borderline
      personality disorder: a critical review of fMRI studies.
AB  - Emotional sensitivity, emotion regulation and impulsivity are fundamental topics
      in research of borderline personality disorder (BPD). Studies using fMRI
      examining the neural correlates concerning these topics is growing and has just
      begun understanding the underlying neural correlates in BPD. However, there are
      strong similarities but also important differences in results of different
      studies. It is therefore important to know in more detail what these differences
      are and how we should interpret these. In present review a critical light is shed
      on the fMRI studies examining emotional sensitivity, emotion regulation and
      impulsivity in BPD patients. First an outline of the methodology and the results
      of the studies will be given. Thereafter important issues that remained
      unanswered and topics to improve future research are discussed. Future research
      should take into account the limited power of previous studies and focus more on
      BPD specificity with regard to time course responses, different regulation
      strategies, manipulation of self-regulation, medication use, a wider range of
      stimuli, gender effects and the inclusion of a clinical control group. 

PMID- 25616187
TI  - A temperature-jump NMR probe setup using rf heating optimized for the analysis of
      temperature-induced biomacromolecular kinetic processes.
AB  - A novel temperature jump (T-jump) probe operational at B(0) fields of 600 MHz
      (14.1 Tesla) with an integrated cage radio-frequency (rf) coil for rapid (<1 s)
      heating in high-resolution (HR) liquid-state NMR-spectroscopy is presented and
      its performance investigated. The probe consists of an inner 2.5 mm "heating
      coil" designed for generating rf-electric fields of 190-220 MHz across a lossy
      dielectric sample and an outer two coil assembly for (1)H-, (2)H- and (15)N
      nuclei. High B(0) field homogeneities (0.7 Hz at 600 MHz) are combined with high
      heating rates (20-25 K/s) and only small temperature gradients (<+/-1.5 K, 3s
      after 20 K T-jump). The heating coil is under control of a high power rf
      amplifier within the NMR console and can therefore easily be accessed by the
      pulse programmer. Furthermore, implementation of a real-time setup including
      synchronization of the NMR spectrometer's air flow heater with the rf-heater used
      to maintain the temperature of the sample is described. Finally, the
      applicability of the real-time T-jump setup for the investigation of biomolecular
      kinetic processes in the second-to-minute timescale is demonstrated for samples
      of a model 14mer DNA hairpin and a (15)N-selectively labeled 40nt hsp17-RNA
      thermometer.

PMID- 25616188
TI  - Evaluation of the sinks and sources of atmospheric CO2 by artificial upwelling.
AB  - Artificial upwelling is considered a promising way to reduce the accumulation of
      anthropogenic carbon dioxide in the atmosphere. This practice could transport
      nutrient-rich deep water to the euphotic zone, enhance phytoplankton growth and
      consequently increase organic carbon exportation to the deep ocean via the
      biological pump. However, only a few studies quantitatively assess changes in
      oceanic CO2 uptake resulting from artificial upwelling. This article uses a
      simulation to examine the effect of hypothetical artificial upwelling-induced
      variations of CO2 fugacity in seawater (fCO2) using observed carbon and nutrient
      data from 14 stations, ranging from 21 to 43 degrees N, in the West Philippine
      Sea (WPS), the East China Sea (ECS) and the Sea of Japan. Calculations are based
      on two basic assumptions: First, a near-field mixing of a nutrient-rich deep
      ocean water plume in a stratified ocean environment is assumed to form given the
      presence of an artificial upwelling devise with appropriate technical parameters.
      Second, it is assumed that photosynthesis of marine phytoplankton could deplete
      all available nutrients following the stoichiometry of the modified Redfield
      ratio C/H/O/N/S/P=103.1/181.7/93.4/11.7/2.1/1. Results suggest artificial
      upwelling has significant effects on regional changes in sea-air differences
      (DeltafCO2sea-air) and the carbon sequestration potential (DeltafCO2mixed-amb).
      Large variations of DeltafCO2sea-air and DeltafCO2mixed-amb are shown to be
      associated with different regions, seasons and technical parameters of the
      artificial upwelling device. With proper design, it is possible to reverse the
      contribution of artificial upwelling from a strong CO2 source to sink. Thus,
      artificial upwelling has the potential to succeed as a geoengineering technique
      to sequester anthropogenic CO2, with appropriate technical parameters in the
      right region and season. 

PMID- 25616189
TI  - Using chemical, microbial and fluorescence techniques to understand contaminant
      sources and pathways to wetlands in a conservation site.
AB  - Nutrients and faecal contaminants can enter wetland systems in a number of ways,
      with both biological and potentially human-health implications. In this study we
      used a combination of inorganic chemistry, dissolved organic matter (DOM)
      fluorescence and Escherichia coli and total coliform (TC) count techniques to
      study the sources and multiple pathways of contamination affecting a designated
      sand dune site of international conservation importance, surrounded by
      agricultural land. Analysis of stream samples, groundwater and dune slack
      wetlands revealed multiple input pathways. These included riverbank seepage,
      runoff events and percolation of nutrients from adjacent pasture into the
      groundwater, as well as some on-site sources. The combined techniques showed that
      off-site nutrient inputs into the sand dune system were primarily from
      fertilisers, revealed by high nitrate concentrations, and relatively low
      tryptophan-like fulvic-like ratios<0.4Ramanunits (R.U.). The E. coli and TC
      counts recorded across the site confirm a relatively minor source of bacterial
      and nutrient inputs from on-site grazers. Attenuation of the nutrient
      concentrations in streams, in groundwater and in run-off inputs occurs within the
      site, restoring healthier groundwater nutrient concentrations showing that
      contaminant filtration by the sand dunes provides a valuable ecosystem service.
      However, previous studies show that this input of nutrients has a clear adverse
      ecological impact.

PMID- 25616190
TI  - Exposure to airborne particulate matter in the subway system.
AB  - The Barcelona subway system comprises eight subway lines, at different depths,
      with different tunnel dimensions, station designs and train frequencies. An
      extensive measurement campaign was performed in this subway system in order to
      characterise the airborne particulate matter (PM) measuring its concentration and
      investigating its variability, both inside trains and on platforms, in two
      different seasonal periods (warmer and colder), to better understand the main
      factors controlling it, and therefore the way to improve air quality. The
      majority of PM in the underground stations is generated within the subway system,
      due to abrasion and wear of rail tracks, wheels and braking pads caused during
      the motion of the trains. Substantial variation in average PM concentrations
      between underground stations was observed, which might be associated to different
      ventilation and air conditioning systems, characteristics/design of each station
      and variations in the train frequency. Average PM2.5 concentrations on the
      platforms in the subway operating hours ranged from 20 to 51 and from 41 to 91
      MUg m(-3) in the warmer and colder period, respectively, mainly related to the
      seasonal changes in the subway ventilation systems. The new subway lines with
      platform screen doors showed PM2.5 concentrations lower than those in the
      conventional system, which is probably attributable not only to the more advanced
      ventilation setup, but also to the lower train frequency and the design of the
      stations. PM concentrations inside the trains were generally lower than those on
      the platforms, which is attributable to the air conditioning systems operating
      inside the trains, which are equipped with air filters. This study allows the
      analysis and quantification of the impact of different ventilation settings on
      air quality, which provides an improvement on the knowledge for the general
      understanding and good management of air quality in the subway system.

PMID- 25616191
TI  - Effects of historic metal(loid) pollution on earthworm communities.
AB  - The effects of metal(loid)s (Pb, Cd, Cu, Zn, As and Sb) from atmospheric fallout
      on earthworm communities were investigated in a fallow meadow located close to a
      60-year-old lead recycling factory. We examined abundance and species diversity
      as well as the ratio of adult-to-juvenile earthworms, along five 140 m parallel
      transects. The influence of soil pollution on the earthworm community at the plot
      scale was put in context by measuring some physico-chemical soil characteristics
      (OM content, N content, pH), as well as total and bioavailable metal(loid)
      concentrations. Earthworms were absent in the highly polluted area (concentration
      from 30,000 to 5000 mg Pb.kg(-1) of dried soil), just near the factory (0-30 m
      area). A clear and almost linear relationship was observed between the proportion
      of juvenile versus mature earthworms and the pollution gradient, with a greater
      proportion of adults in the most polluted zones (only adult earthworms were
      observed from 30 to 50 m). Apporectodea longa was the main species present just
      near the smelter (80% of the earthworms were A. longa from 30 to 50 m). The
      earthworm density was found to increase progressively from five individuals.m(-2)
      at 30 m to 135 individuals.m(-2) at 140 m from the factory. On average,
      metal(loid) accumulation in earthworm tissues decreased linearly with distance
      from the factory. The concentration of exchangeable metal(loid)s in earthworm
      surface casts was higher than that of the overall soil. Finally, our field study
      clearly demonstrated that metal(loid) pollution has a direct impact on earthworm
      communities (abundance, diversity and proportion of juveniles) especially when Pb
      concentrations in soil were higher than 2050 mg.kg(-1).

PMID- 25616193
TI  - Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.
AB  - Monitoring chemical reactions is the key to controlling chemical processes where
      NMR can provide support. High-field NMR gives detailed structural information on
      chemical compounds and reactions; however, it is expensive and complex to
      operate. Conversely, low-field NMR instruments are simple and relatively
      inexpensive alternatives. While low-field NMR does not provide the detailed
      information as the high-field instruments as a result of their smaller chemical
      shift dispersion and the complex secondary coupling, it remains of practical
      value as a process analytical technology (PAT) tool and is complimentary to other
      established methods, such as ReactIR and Raman spectroscopy. We have tested a
      picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to
      monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a
      Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification
      is a relatively simple reaction run at high concentration and served as proof of
      concept. The Suzuki coupling is an example of a more complex, commonly used
      reaction involving overlapping signals. Finally, the oxime formation involved a
      reaction in two phases that cannot be monitored by other PAT tools. Here, we
      discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz
      by 1D (1) H NMR. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25616194
TI  - Exploring opportunities for healthy aging among older persons with a history of
      homelessness in Toronto, Canada.
AB  - Within the areas of literature on both population aging and health and
      homelessness, little attention has been given to the opportunities and barriers
      to healthy aging among older persons with a history of homelessness. Set in the
      context of inner-city Toronto, Canada, this article reports on the findings from
      qualitative interviews with 29 formerly homeless older persons. The findings
      illustrate participants' experiences of positive health change since moving into
      a stable housing environment and the aspects of housing they perceive to have
      improved their health and wellbeing. The qualitative findings also draw attention
      to the ongoing barriers to healthy aging that can be experienced among older
      persons with a history of homelessness. Overall, this study draws on the lived
      experiences of formerly homeless older persons to offer a better understanding of
      the long-term effects of homelessness on health, wellbeing, and aging. 

PMID- 25616195
TI  - Action on the social determinants of health: views from inside the policy
      process.
AB  - It is now well documented that many of the key drivers of health reside in our
      everyday living conditions. In the last two decades, public health has urged
      political action on these critical social determinants of health (SDH). As noted
      by the World Health Organisation, encouraging action in this area is challenging.
      Recent research has argued that public health researchers need to gain a deeper
      understanding of the complex and changing rationalities of policymaking. This, it
      seems, is the crucial next step for social determinants of health research. In
      this paper, we turn our attention to the practitioners of 'the art of
      government', in order to gain insight into how to secure upstream change for the
      SDH. Through interviews with policy actors (including politicians, senior
      government advisors, senior public servants and experienced policy lobbyists) the
      research sought to understand the nature of government and policymaking, as it
      pertains to action on the SDH. Through exploring the policy process, we examine
      how SDH discourses, evidence and strategies align with existing policy processes
      in the Australian context. Participants indicated that approaches to securing
      change that are based on linear conceptualisations of the policy process (as
      often found in public health) may be seen as 'out of touch' with the messy
      reality of policymaking. Rather, a more dialogic approach that embraces
      philosophical and moral reasoning (alongside evidence) may be more effective.
      Based on our findings, we recommend that SDH advocates develop a deeper awareness
      of the political and policy structures and the discursive conventions they seek
      to influence within specific settings. 

PMID- 25616192
TI  - Rationale and design of the Feeding Dynamic Intervention (FDI) study for self
      regulation of energy intake in preschoolers.
AB  - In 2011, the Institute of Medicine Early Childhood Prevention Policies Report
      identified feeding dynamics as an important focus area for childhood obesity
      prevention and treatment. Feeding dynamics includes two central components: (1)
      caregiver feeding practices (i.e., determining how, when, where, and what they
      feed their children) and (2) child eating behaviors (i.e., determining how much
      and what to eat from what food caregivers have provided). Although there has been
      great interest in overweight and obesity prevention and treatment in young
      children, they have not focused comprehensively on feeding dynamics.
      Interventions on feeding dynamics that reduce caregivers' excessive controlling
      and restrictive feeding practices and encourage the development of children's
      self-regulation of energy intake may hold promise for tackling childhood obesity
      especially in the young child but currently lack an evidence base. This
      manuscript describes the rationale and design for a randomized controlled trial
      designed to compare a group of mothers and their 3-to 5-year old children who
      received an intervention focused primarily on feeding dynamics called the Feeding
      Dynamic Intervention (FDI) with a Wait-list Control Group (WLC). The primary aim
      of the study will be to investigate the efficacy of the FDI for decreasing Eating
      in the Absence of Hunger (EAH) and improving energy compensation (COMPX). The
      secondary aim will be to examine the effect of the FDI in comparison to the WLC
      on maternal self-reported feeding practices and child satiety responsiveness. 

PMID- 25616196
TI  - The effect of long-term corticosterone treatment on blood cell differentials and
      function in laboratory and wild-caught amphibian models.
AB  - The effect of long-term stress on amphibian immunity is not well understood. We
      modeled a long-term endocrine stress scenario by elevating plasma corticosterone
      in two species of amphibians and examined effects on white blood cell
      differentials and innate immune activity. Plasma corticosterone was elevated in
      American bullfrogs (Lithobates catesbeianus) by surgically implanting
      corticosterone capsules and in African clawed frogs (Xenopus laevis) by immersion
      in corticosterone-treated water. To provide a context for our results within
      endogenous corticosterone fluctuations, diurnal plasma corticosterone cycles were
      determined. A daily low of corticosterone was observed in X. laevis at 12:00,
      while a significant pattern was not observed in L. catesbeianus. Elevated plasma
      corticosterone levels increased the ratio of peripheral neutrophils to
      lymphocytes, in both species, and decreased eosinophil concentrations in L.
      catesbeianus over a long-term period. Whole blood oxidative burst generally
      correlated with neutrophil concentrations, and thus was increased with
      corticosterone treatment, significantly in L. catesbeianus. In L. catesbeianus,
      an endogenous response of eosinophils and lymphocytes to implanted empty (sham)
      capsules was observed, but this effect was attenuated by corticosterone.
      Peripheral monocyte and basophil concentrations were not significantly altered by
      corticosterone treatment in either species. Our results show that long-term
      stress can alter amphibian immune parameters for extended periods and may play a
      role in susceptibility to disease. 

PMID- 25616197
TI  - Insulin/IGF signaling and its regulation in Drosophila.
AB  - Taking advantage of Drosophila as a genetically tractable experimental animal
      much progress has been made in our understanding of how the insulin/IGF signaling
      (IIS) pathway regulates development, growth, metabolism, stress responses and
      lifespan. The role of IIS in regulation of neuronal activity and behavior has
      also become apparent from experiments in Drosophila. This review briefly
      summarizes these functional roles of IIS, and also how the insulin producing
      cells (IPCs) are regulated in the fly. Furthermore, we discuss functional aspects
      of the spatio-temporal production of eight different insulin-like peptides (DILP1
      8) that are thought to act on one known receptor (dInR) in Drosophila. 

PMID- 25616198
TI  - Sensitivity analysis, dominant factors, and robustness of the ECETOC TRA v3,
      Stoffenmanager 4.5, and ART 1.5 occupational exposure models.
AB  - Occupational exposure modeling is widely used in the context of the E.U.
      regulation on the registration, evaluation, authorization, and restriction of
      chemicals (REACH). First tier tools, such as European Centre for Ecotoxicology
      and TOxicology of Chemicals (ECETOC) targeted risk assessment (TRA) or
      Stoffenmanager, are used to screen a wide range of substances. Those of concern
      are investigated further using second tier tools, e.g., Advanced REACH Tool
      (ART). Local sensitivity analysis (SA) methods are used here to determine
      dominant factors for three models commonly used within the REACH framework:
      ECETOC TRA v3, Stoffenmanager 4.5, and ART 1.5. Based on the results of the SA,
      the robustness of the models is assessed. For ECETOC, the process category (PROC)
      is the most important factor. A failure to identify the correct PROC has severe
      consequences for the exposure estimate. Stoffenmanager is the most balanced model
      and decision making uncertainties in one modifying factor are less severe in
      Stoffenmanager. ART requires a careful evaluation of the decisions in the source
      compartment since it constitutes ~75% of the total exposure range, which
      corresponds to an exposure estimate of 20-22 orders of magnitude. Our results
      indicate that there is a trade off between accuracy and precision of the models.
      Previous studies suggested that ART may lead to more accurate results in well
      documented exposure situations. However, the choice of the adequate model should
      ultimately be determined by the quality of the available exposure data: if the
      practitioner is uncertain concerning two or more decisions in the entry
      parameters, Stoffenmanager may be more robust than ART. 

PMID- 25616199
TI  - Association of subarachnoid hemorrhage and phentermine usage: Coincidence, not
      causation.

PMID- 25616200
TI  - Surgical treatment of advanced gallbladder cancer.
AB  - OBJECTIVE: Radical lymph node dissection in surgery for advanced gallbladder
      cancer is controversial. The purpose of this study is to evaluate the different
      extent of lymph node dissection for N2 stage gallbladder cancer patients.
      PATIENTS AND METHODS: A retrospective analysis was made of 60 patients with N2
      stage who underwent standard regional lymphadenectomy (SRLN) and extended
      regional lymphadenectomy (ERLN). Between September 2000 and June 2011, 60
      advanced gallbladder cancer patients with N2 stage of lymph node metastasis were
      included in this study. The curative effects with different extent of
      lymphadenctomy for lymph node N2 stage of gallbladder cancer patients were
      compared. RESULTS: The median survival time was 34.83 months in the SRLN group
      and 30.28 months in the ERLN group. There was no significant difference of
      survival rate between SRLN and ERLN group (P=0.51). Postoperative major morbidity
      and mortality rates were 64.3% and 7.14% in the SRLN group, 81.3% and 9.34% in
      the ERLN group, respectively. Moreover, the number of positive lymph nodes and
      chemotherapy were found to correlate with survival on univariate analyses
      (P<0.05). CONCLUSIONS: For advanced gallbladder patients with N2 stage lymph node
      metastasis, ERLN cannot provide a significant survival benefit over SRLN and the
      rate of morbidity and mortality in ERLN is exceptionally high. ERLN therefore
      should not be considered in the advanced gallbladder cancers with N2 stage.

PMID- 25616201
TI  - Adjuvant chemoradiation plus intraoperative radiotherapy versus adjuvant
      chemoradiation alone in patients with locally advanced rectal cancer.
AB  - OBJECTIVES: To document the efficacy of intraoperative radiotherapy (IORT)
      followed by adjuvant chemoradiation in the management of locally advanced rectal
      cancer. MATERIALS AND METHODS: A total of 148 patients with pT4N0/T1-4N+ rectal
      adenocarcinoma were enrolled. Seventy-seven patients received total mesorectal
      excision surgery followed by adjuvant chemoradiation alone, 71 patients received
      total mesorectal excision surgery followed by IORT (range, 10 to 20 Gy) and
      adjuvant chemoradiation. RESULTS: The 5-year local control (LC) and disease-free
      survival were 79.2% versus 89.7% (P=0.032), 58.5% versus 69.0% (P=0.049) for
      external-beam radiation (EBRT) and IORT+EBRT groups, respectively. Multivariate
      analysis revealed that adjuvant IORT has a trend toward improvement of LC
      (P=0.079); 5 (3%) patients (EBRT n=2; IORT n=3) experienced incomplete intestinal
      obstruction and 3 patients had chronic diarrhea. There was no clinically relevant
      neuropathy or sacral osteoradionecrosis. Hydronephrosis occurred in 13 patients
      (EBRT n=8; IORT+EBRT n=5), 8 of whom had documented concomitant disease
      recurrence. CONCLUSIONS: For patients with locally advanced rectal cancer, higher
      radiation dose may contribute to the improvement of both LC and disease-free
      survival, without significantly increasing the incidence of acute and long-term
      complications compared with adjuvant chemoradiotherapy alone.

PMID- 25616202
TI  - Fast neutron radiotherapy in the treatment of malignant pleural mesothelioma.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is a fatal disease lacking
      standardized treatment. We describe the use of fast neutron radiation therapy in
      MPM patients referred to the Department of Radiation Oncology at the University
      of Washington Medical Center. MATERIALS AND METHODS: Retrospective chart review
      of MPM patients receiving neutron radiotherapy treatment from 1980 to 2012.
      RESULTS: A total of 30 MPM patients received fast neutron radiotherapy as part of
      their treatment regimen. Median age at diagnosis was 59.6 years (range, 46.6 to
      72.3 y). Eighteen patients received fast neutron radiotherapy as a component of
      trimodality treatment. Median overall survival was 20.3 months (range, 5.5 to
      73.3 mo) with 1 patient censored at 34.8 months and all other patients with
      confirmed dates of death. One patient receiving radiotherapy alone as a
      palliative measure died during radiation treatment. One patient was unable to
      tolerate radiotherapy and stopped before completing prescribed treatment. On
      univariate analysis, Brigham Stage at presentation was a significant predictor of
      survival (P<0.01). No significant differences in survival were observed when
      comparing patients who received trimodality treatment compared to those who did
      not. CONCLUSIONS: Fast neutron radiotherapy may be utilized in the management of
      MPM patients. However, treatment with fast neutron radiotherapy did not
      significantly improvement outcome, even when used in a trimodality regimen.

PMID- 25616203
TI  - Phase II study of nab-paclitaxel and bevacizumab as first-line therapy for
      patients with unresectable stage III and IV melanoma.
AB  - OBJECTIVES: This study was an open-label multicenter phase II trial to
      investigate the efficacy and safety of nab-paclitaxel and bevacizumab as first
      line therapy in patients with histologically confirmed unresectable metastatic
      melanoma. METHODS: The treatment regimen consisted of a 28-day cycle in which
      patients received nab-paclitaxel, 150 mg/m through intravenous (IV) infusion
      weekly for 3 weeks and bevacizumab, 10 mg/kg IV every 2 weeks without a rest
      period. The 28-day cycle was repeated until there was unacceptable toxicity or
      disease progression. If 1 drug had to be stopped because of toxicity, treatment
      was continued with the other drug until disease progression or unacceptable
      toxicity. The primary endpoint was the progression-free survival rate (PFS) at 4
      months. RESULTS: Fifty patients were enrolled. The PFS rate at 4 months was 75%.
      The median PFS was 7.6 months and the median overall survival was 16.8 months
      with a median duration follow-up of 41.6 months. The overall survival rate was
      64% at 1 year and 30% at 2 years. Ten patients (20%) remain alive. The objective
      response rate was 36%. Common adverse events associated with this regimen were
      peripheral neuropathy, fatigue, alopecia, and gastrointestinal disorders.
      CONCLUSIONS: In this phase II multicenter study, this doublet had significant
      activity in patients with metastatic melanoma, and was well tolerated. These
      results are promising and follow-up trials to further explore this regimen are
      warranted.

PMID- 25616204
TI  - Immune-priming of the tumor microenvironment by radiotherapy: rationale for
      combination with immunotherapy to improve anticancer efficacy.
AB  - A clear contribution of the immune system to eradication of tumors has been
      supported by recent developments in the field of immunotherapy. Durable clinical
      responses obtained after treatment with immunomodulatory agents such as
      ipilimumab (Yervoy) and anti-PD-1 antibody (BMS-936558), have established that
      harnessing the immune response against chemoresistant tumors can result in their
      complete eradication. However, only a subset of patients benefit from these
      therapeutic approaches. Accumulating evidence suggests that tumors with a
      preexisting active immune microenvironment might have a better response to
      immunotherapy. In a number of preclinical and clinical studies, many cytotoxic
      agents elicit changes within tumors and their microenvironment that may make
      these malignant cells more sensitive to an efficient immune cell attack.
      Therefore, it is plausible that combining immunotherapy with standard anticancer
      therapies such as chemotherapy or radiotherapy will provide synergistic antitumor
      effects. Despite a large collection of preclinical data, the immune mechanisms
      that might contribute to the efficacy of conventional cytotoxic therapies and
      their combinations with immunotherapeutic approaches have not yet been
      extensively studied in the clinical setting and warrant further investigation.
      This review will focus on current knowledge of the immunomodulatory effects of
      one such cytotoxic treatment, radiotherapy, and explore different pathways by
      which its combination with immunomodulatory antibodies might contribute toward
      more efficacious antitumor immunity. 

PMID- 25616205
TI  - Development of END-of-Life ScorING-System to identify critically ill patients
      after initial critical care who are highly likely to die: a pilot study.
AB  - BACKGROUND: High quality palliative care should be provided for the dying
      patients in the intensive care unit (ICU). The aim of this pilot study is to
      develop a scoring system, the "END-of-Life ScorING-System" (ENDING-S), that may
      help to identify ICU patients at very high risk of dying after initial response
      to the intensive treatments and which could be used to facilitate palliative
      care. METHODS: The characteristics of longer-term ICU patients (>4 days) who are
      at very high risk of dying were identified through an analysis of the literature
      and developed in a retrospective cohort of patients. ENDING-S Score was developed
      through a multivariate analysis. Model accuracy was tested through ROC and Hosmer
      Lemeshow analysis for model discrimination and calibration respectively. Cross
      validation was used to provide internal model validation. RESULTS: Potential
      predictors of death were identified and applied to 80 ICU patients. Significant
      variables in the multivariate analysis were the ratio of the ICU days in which
      the patient needs mechanical ventilation or vasoactive drugs divided by the total
      ICU days, the total ICU length of stay, and current sepsis. Analysis of accuracy
      showed a ROC-AUC equals to 0.98 (95% CI, 0.97 to 1), and agreement between the
      predicted probability and the observed frequency of death in the ICU was observed
      (P>0.05 at Hosmer-Lemeshow test). The internal validation confirms these results.
      CONCLUSION: In these preliminary results, ENDING-s shows acceptable calibration
      and discrimination properties. ENDING-S may raise awareness among ICU physicians
      about the importance of integrating palliative care into ICU daily practice.

PMID- 25616206
TI  - Intravenous infusion of magnesium sulfate and postoperative analgesia in total
      knee arthroplasty.
AB  - BACKGROUND: The effectiveness of combining magnesium (Mg) administration with
      both general and spinal anesthesia to reduce postoperative pain and analgesic
      consumption is still debated. We evaluated the effects of an intravenous (IV)
      infusion of Mg sulphate on analgesic consumption and postoperative pain score
      after total knee arthroplasty performed under spinal anesthesia. METHODS: We
      studied 40 patients who underwent spinal anesthesia with bupivacaine plus
      morphine. Patients were randomly assigned to two groups, each of 20 patients, who
      received either treatment (i.e., intravenous Mg sulphate 40 mg kg(-1) followed by
      an infusion of 10 mg kg(-1) h(-1)), or the same amounts of isotonic saline
      (controls). Irrespective of the group of randomization, all patients received
      postoperative paracetamol, ketorolac, and patient-controlled analgesia with
      morphine. RESULTS: The Mg postoperative blood level was 0.85 +/- 0.02 mmol/L and
      1.25 +/- 0.11 mmol/L for C and Mg groups, respectively (P<0.001). Sensory level
      of the spinal block, height of spinal block, mean time to first pain and
      incidence of PONV were similar in the two groups. Morphine consumption did not
      show any statistically significant difference between the two groups. The pain
      score was not significantly different between the two groups. No severe adverse
      effects were recorded after Mg infusion. CONCLUSION: IV perioperative
      administration of Mg did not influence postoperative pain control and analgesic
      consumption after total knee arthroplasty. More studies should be performed with
      different intra and postoperative pain protocols to enhance the potential anti
      nociceptive effect of Mg.

PMID- 25616207
TI  - Comparative study of three different supraglottic airway devices in simulated
      difficult airway situations.
AB  - BACKGROUND: Supraglottic airway devices (SAD) provide an effective way for
      managing difficult airways. Numerous SADs have been developed in recent years. We
      compared three SADs utilizing simulated airways. The major aim of this study was
      to provide evidence for the efficacy of SADs in the management of simulated
      difficult airway situations. METHODS: The study utilized an airway simulation
      manikin (Laerdal SimMan(r) 3G) to assess feasibility and time to final placement
      of three different airway devices (the classic laryngeal mask airway [LMA], the
      Laryngeal tube [LT], and the EasyTube(r) [EzT]). Thirty anesthesiologists
      inserted each of the SADs under standard physiologic airway conditions (STD) as
      well as pathological airway conditions, including tongue edema (TE) and trismus
      combined with limited mobility of the cervical spine (TCS), mimicking a patient
      with cramps. RESULTS: In STD and TE, all participants were able to successfully
      place the LMA, LT, and EzT correctly. In TCS, one participant failed to place the
      LMA correctly, whereas six participants failed to place the LT correctly
      (P=0.031). Under STD and TE conditions, we found a significantly longer time to
      final placement with the EzT (P=0.001). Under TCS conditions, there was no
      significant difference between the tested SADs. Under STD conditions, the
      participants rated the LMA best (P<0.001). Under TE and TCS condition, the EzT
      was significantly higher rated (P<0.001). CONCLUSION: The EzT showed benefits in
      two difficult airway situations (TE and TCS) in a prospective manikin study
      amongst anesthesiologists.

PMID- 25616208
TI  - Lights and shadows of palliative sedation in Italy: the role of anesthetists.

PMID- 25616209
TI  - New thermosensitive nanoparticles prepared by biocompatible pegylated aliphatic
      polyester block copolymers for local cancer treatment.
AB  - OBJECTIVE: New pegylated thermosensitive polymers were developed to study them as
      drug vehicles in targeting release nanoparticulate systems of anticancer drugs.
      METHODS: The drug vehicles were prepared in the form of core-shell nanoparticles
      using novel polymeric materials synthesized by copolymerization of poly(propylene
      adipate) (PPAd) and methoxy-polyethylene glycol (mPEG) with different molecular
      weights. The physical and chemical properties of the synthesized mPEG-PPAd
      copolymers were studied using several techniques, and their cytocompatibility was
      evaluated. For drug nanoencapsulation, a water in oil (W/O) emulsification and
      solvent evaporation technique was used and the prepared nanoparticles were
      studied for their physical properties, morphology, drug release and anticancer
      efficacy against cancer cell lines. KEY FINDINGS: The size of the nanoparticles
      lied in a range suitable for tumour targeting. Drug release was affected by the
      composition of polymer, the temperature and pH of the release medium. The release
      results obtained indicate that judicious selection of nanoparticles composition
      may allow for enhanced drug delivery to the tumours following application of
      local hyperthermia. CONCLUSIONS: The paclitaxel-loaded mPEG-PPAd nanoparticles
      were found to be cytotoxic against to the human hepatoma HepG2) and the human
      epithelial (HeLa) cancer cell lines. Enhanced cytotoxicity against the HeLa cells
      was observed at elevated temperature (42 degrees C compared with 37 degrees C),
      providing support for the potential usefulness of the mPEG-PPAd nanoparticles for
      the development of thermo-sensitive anticancer drug delivery systems.

PMID- 25616210
TI  - Simultaneous determination of the novel tyrosine kinase inhibitor meditinib and
      its active metabolite demethylation meditinib in monkey plasma by liquid
      chromatography-tandem mass spectrometry and its application to pharmacokinetic
      studies.
AB  - Meditinib (ME) is a novel tyrosine kinase inhibitor used as an antichronic
      myeloid leukemia drug. A simple, sensitive and specific LC/MS/MS method was
      developed and validated for the analysis of ME and its metabolite demethylation
      meditinib (PI) in monkey plasma using naltrexone as the internal standard. Sample
      preparation involved protein precipitation with methanol. The analysis was
      carried out on an Agilent C8 column (3.5 um, 2.1 * 50 mm). Elution was achieved
      with a mobile phase gradient varying the proportion of a water solution
      containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol
      solution (solvent B) at a flow rate of 300 MUL/min. The method had a linear
      calibration curve over the concentration range of 2-1000 ng/mL for ME and 2-1000
      ng/mL for PI. The lower limits of quantification of ME and PI were 2 and 2 ng/mL,
      respectively. The intra- and inter-day precision values were <15% and accuracy
      values were within +/-10.0%. The mean recoveries of ME and PI from plasma were
      >85%. The assay has been successfully used for pharmacokinetic evaluation of ME
      and PI using the monkey as an animal model, and those data are reported for the
      first time.

PMID- 25616211
TI  - Trace amine-associated receptors: ligands, neural circuits, and behaviors.
AB  - Trace amine-associated receptors (TAARs) are G Protein-Coupled Receptors that
      function as vertebrate olfactory receptors. Like odorant receptors, TAARs
      constitute an ever-evolving sensory subsystem, with individual TAARs recognizing
      particular chemicals and some evoking stereotyped behaviors. Several TAARs
      mediate aversion or attraction towards volatile amines that include the mouse
      odor trimethylamine, the predator odor 2-phenylethylamine, and the death
      associated odor cadaverine. TAAR-expressing sensory neurons achieve monoallelic
      receptor expression, use canonical olfactory signaling molecules, and target a
      dedicated olfactory bulb region. In mouse, TAAR4 and TAAR5 are encoded by
      adjacent genes and localize to adjacent glomeruli, yet mediate opposing
      behaviors. Future studies are needed to understand how TAAR-expressing sensory
      neurons engage higher-order neural circuits to encode odor valence. 

PMID- 25616212
TI  - Temperature sensation in Drosophila.
AB  - Animals use thermosensory systems to achieve optimal temperatures for growth and
      reproduction and to avoid damaging extremes. Thermoregulation is particularly
      challenging for small animals like the fruit fly Drosophila melanogaster, whose
      body temperature rapidly changes in response to environmental temperature
      fluctuation. Recent work has uncovered some of the key molecules mediating fly
      thermosensation, including the Transient Receptor Potential (TRP) channels TRPA1
      and Painless, and the Gustatory Receptor Gr28b, an unanticipated thermosensory
      regulator normally associated with a different sensory modality. There is also
      evidence the Drosophila phototransduction cascade may have some role in
      thermosensory responses. Together, the fly's diverse thermosensory molecules act
      in an array of functionally distinct thermosensory neurons to drive a suite of
      complex, and often exceptionally thermosensitive, behaviors. 

PMID- 25616213
TI  - Perceived recollection of frequent exposure to foods in childhood is associated
      with adulthood liking.
AB  - Food preferences and habits learned at a young age can influence adulthood
      dietary patterns and weight, but the mechanism remains to be elucidated. We
      investigated the effect of perceived recollections of early food experiences on
      current liking for those foods by 670 college students. We showed that the
      perceived recollection of frequent consumption of foods in childhood was
      significantly related to current liking for the vast majority of the foods,
      including nutritious foods such as vegetables. Similarly, parental encouragement
      and modeling was positively related with current liking, even for foods that were
      disliked in childhood. Additionally, perceived recollections of parental
      restriction or forced consumption were significantly negatively related with
      current liking. Lastly, we demonstrated that perceived recollections by college
      students of childhood eating practices were in moderate agreement with those of
      their parents, lending credibility to the retrospective survey methodology in
      determining long-term effects of exposure on current food habits. These findings
      show that the perceived recalled frequency of consumption of foods is one
      determinant of the food preferences of adults, demonstrating a long-term effect
      of frequency of exposure, a finding consistent with experimentally controlled
      short-term studies. Frequent exposure to foods in childhood could be a simple and
      effective way for parents and caregivers to instill healthy eating habits in
      children. 

PMID- 25616214
TI  - Eating fruits and vegetables. An ethnographic study of American and French family
      dinners.
AB  - The French eat more fruits and vegetables than Americans and have lower rates of
      childhood obesity. This ethnographic study compares various aspects of meal
      environment in sixteen households in LA, California and Paris, France, and offers
      insights on the relationship between local practices and preferences and
      children's consumption of fruits and vegetables. Our analysis of video-recorded
      naturalist data reveals that the consumption of fruits and vegetables is linked
      to the cultural organization of dinner--what, when and how food is served--and to
      local beliefs about children's eating practices. We also found that the French
      model for dinnertime prioritizes the eating of fruits and vegetables more than
      the American model does. We propose that local eating models should be taken into
      account in research on childhood obesity and in prevention programs.

PMID- 25616215
TI  - APOE E4 constrains engagement of encoding-related compensatory networks in
      amnestic mild cognitive impairment.
AB  - People with amnestic mild cognitive impairment (aMCI), compared to healthy older
      adults (HO), benefit less from semantic congruent cues during episodic encoding.
      The presence of the apolipoprotein E (APOE) E4 makes this congruency benefit
      smaller, but the neural correlates of this deficit are unknown. Here, we
      estimated the source generators of EEG oscillatory activity associated with
      successful encoding of face-location associations preceded by semantically
      congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of
      which were E4 carriers (E4(+) ) and 18 E4 noncarriers (E4(-) ). Source estimation
      was performed in those spectrotemporal windows where the power of low-alpha, high
      alpha, and beta oscillatory activity differed either between congruent and
      incongruent faces or between groups. Differences in high-alpha and beta
      oscillatory dynamics indicated that aMCI E4(+) are unable to activate lateral
      regions of the temporal lobe involved in associative memory and congruency
      benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated
      additional regions relative to HO, through alpha oscillations. However, only
      activation in a distributed fronto-temporo-parietal network in E4 noncarriers was
      paralleled by enhanced memory. On the contrary, the redundant prefrontal
      activation shown by aMCI E4(+) did not prevent performance from decreasing. These
      results indicate that the effect of aMCI-related degeneracy on functional
      networks is constrained by the presence of APOE E4. Whereas individuals with aMCI
      E4(-) activate attentional, perceptual and semantic compensatory networks, aMCI
      E4(+) show reduced processing efficiency and capacity.

PMID- 25616216
TI  - Characterization of nuclear PTEN and its post translational modifications.
AB  - Somatic loss-of-function mutations of PTEN are found in a variety of human
      malignancies. Our recent work demonstrated that the nuclear function of PTEN is
      implicated in the maintenance of genome integrity. Proper subcellular
      localization of PTEN following genotoxic stress is coordinated by a cellular
      mechanism that involves post-translational modification by SUMOylation and ATM
      mediated phosphorylation. Here we summarize biochemical and cell-based
      methodologies that can be used to characterize the SUMOylation and
      phosphorylation state of nuclear PTEN in the context of DNA damage. In addition,
      we describe assays to determine the biological function of SUMO-PTEN in
      homologous recombination DNA repair. These methods will help elucidate the
      precise molecular mechanisms of PTEN's role in the maintenance of genomic
      stability. 

PMID- 25616217
TI  - The reference ballistic imaging database revisited.
AB  - A reference ballistic image database (RBID) contains images of cartridge cases
      fired in firearms that are in circulation: a ballistic fingerprint database. The
      performance of an RBID was investigated a decade ago by De Kinder et al. using
      IBIS((r)) HeritageTM technology. The results of that study were published in this
      journal, issue 214. Since then, technologies have evolved quite significantly and
      novel apparatus have become available on the market. The current research article
      investigates the efficiency of another automated ballistic imaging system,
      Evofinder((r)) using the same database as used by De Kinder et al. The results
      demonstrate a significant increase in correlation efficiency: 38% of all matches
      were on first position of the Evofinder correlation list in comparison to
      IBIS((r)) HeritageTM where only 19% were on the first position. Average
      correlation times are comparable to the IBIS((r)) HeritageTM system. While
      Evofinder((r)) demonstrates specific improvement for mutually correlating
      different ammunition brands, ammunition dependence of the markings is still
      strongly influencing the correlation result because the markings may vary
      considerably. As a consequence a great deal of potential hits (36%) was still far
      down in the correlation lists (positions 31 and lower). The large database was
      used to examine the probability of finding a match as a function of correlation
      list verification. As an example, the RBID study on Evofinder((r)) demonstrates
      that to find at least 90% of all potential matches, at least 43% of the items in
      the database need to be compared on screen and this for breech face markings and
      firing pin impression separately. These results, although a clear improvement to
      the original RBID study, indicate that the implementation of such a database
      should still not be considered nowadays. 

PMID- 25616218
TI  - Validation of JWH-018 and its metabolites in blood and urine by UPLC-MS/MS:
      Monitoring in forensic cases.
AB  - The herbal products referred to as 'Spice' have been used as 'legal alternatives'
      to cannabis worldwide since 2004. The first synthetic cannabinoid JWH-018 was
      detected in 'Spice' products in 2008, and has been banned by many legal
      authorities since the beginning of 2009. In order to prove use of JWH
      cannabinoids (JWHs), specific and robust methods were needed. We have developed a
      specific and reliable method for the detection and quantification of JWH-018, JWH
      018 N-pentanoic acid, and JWH-018 N-(5-hydroxypentyl) in blood and urine using
      solid-phase extraction followed by UPLC-MS/MS analysis. The method has been
      validated in terms of linearity (0.1-50ng/mL), selectivity, intra-assay and inter
      assay accuracy and precision (CV<15%), recovery (85-98%), limits of detection
      (LOD) (0.08-0.14ng/mL), and quantification (LOQ) (0.10-0.21ng/mL). Matrix
      effects, stability, and process efficiency were also assessed. The method has
      been applied to 868 authentic samples received by the Department of Chemistry
      (Istanbul) in the Council of Forensic Medicine of the Ministry of Justice. 

PMID- 25616219
TI  - Cut-off proposal for the detection of ketamine in hair.
AB  - Ketamine is a powerful anesthetic drug used in both human and veterinary surgery,
      but it is also commonly misused because of its psychotropic properties. Since the
      abuse of this drug has been reported in many countries worldwide, its
      determination in hair samples is offered as a specialist test by hundreds of
      laboratories. However, unlike other common drugs of abuse, a cut-off level for
      ketamine in hair has not been fixed yet. Therefore, aim of this study is to
      propose a concentration value for ketamine in hair analysis, in order to
      discriminate between chronic and occasional use, and between active use and
      external contamination. After considering the chemical properties of this
      molecule, and the experimental data collected in our laboratory or reported in
      several other published studies, we propose a cut-off level of 0.5ng/mg, as
      indicative of repeated exposure to ketamine. Additionally, we suggest that the
      detection of the metabolite norketamine should be mandatory to prove active
      intake and exclude false positive result from external contamination. Thus, a
      reasonable cut-off value for norketamine could be fixed at 0.1ng/mg, while the
      minimal concentration ratio norketamine/ketamine may be positively established at
      0.05. 

PMID- 25616221
TI  - Evaluation of Muscodor suthepensis strain CMU-Cib462 as a postharvest biofumigant
      for tangerine fruit rot caused by Penicillium digitatum.
AB  - BACKGROUND: This study investigated both the in vitro and in vivo biofumigant
      ability of the endophytic fungus Muscodor suthepensis CMU-Cib462 to control
      Penicillium digitatum, the main cause of tangerine fruit rot. RESULTS: Volatile
      compounds from M. suthepensis inhibited mycelial growth of the pathogen. The most
      abundant compound was 2-methylpropanoic acid, followed by 3-methylbutan-1-ol.
      They showed median effective doses (ED50) on P. digitatum growth of 74.91 +/-
      0.73 and 250.29 +/- 0.29 uL L(-1) airspace respectively. Rye grain was found to
      be a suitable solid medium for M. suthepensis inoculum production. The results
      indicated that mycofumigation with a 30 g rye grain culture of M. suthepensis for
      12 h controlled tangerine fruit rot. The percentage weight loss and soluble
      solids concentration of fumigated tangerines were similar to those of non
      infected and non-fumigated fruits. CONCLUSION: Muscodor suthepensis has potential
      as a biofumigant for controlling postharvest disease of tangerine fruit.

PMID- 25616220
TI  - BDCA3 expression is associated with high IFN-lambda production by CD34(+)-derived
      dendritic cells generated in the presence of GM-CSF, IL-4, and/or TGF-beta.
AB  - High BDCA3 expression is associated with a specific human IFN-lambda-producing
      dendritic cell (DC) subset. However, BDCA3 has also been detected on other DC
      subsets. Thus far, development and function of BDCA3 expression on DCs remains
      poorly understood. Human Langerhans cells (LCs) and interstitial DCs (intDCs) can
      be generated in vitro by differentiation of CD34(+) hematopoietic progenitors via
      distinct precursor DCs (preDCs), CD1a(+) preDCs, and CD14(+) preDCs,
      respectively. Here, we identified BDCA3 expression in this well-known GM-CSF/TNF
      alpha-driven culture system and described the effect of IL-4 and/or TGF-beta on
      induction of BDCA3 expression. In control or TGF-beta cultures, BDCA3 was only
      detected on CD14(+) preDC-derived intDCs. IL-4 induced BDCA3 expression in both
      CD14(+)-derived and CD1a(+)-derived cultures. TGF-beta and IL-4 together further
      increased CD14(+)-derived and CD1a(+)-derived BDCA3(+) DC frequencies, which
      partly expressed CLEC9A, but were not identical to the BDCA3(high) CLEC9A(+) DC
      subset in vivo. Importantly, BDCA3(+) cells, but not BDCA3(-) cells, in this
      system produced high IFN-lambda levels upon polyinosinic:polycytidylic acid
      (polyI:C) stimulation. This culture system, in which BDCA3 expression is
      preferentially associated with the intDC lineage and IFN-lambda-producing
      capacity, will greatly contribute to further research on the function and
      regulation of BDCA3 expression and IFN-lambda production by DCs.

PMID- 25616222
TI  - Classification models based on the level of metals in hair and nails of laryngeal
      cancer patients: diagnosis support or rather speculation?
AB  - The etiology of cancer is complex, and the disturbances in toxic and essential
      metals homeostasis are among many of the factors that lead to the development of
      malignancy. The aim of this study is to investigate the relationship between
      cancer risk and element status as well as cancer risk and external factors, such
      as diet, smoking and drinking habits, in order to support diagnosis of cancer.
      The samples of hair and nails obtained from patients with larynx cancer and
      healthy subjects were analyzed. Essential elements (Ca, Cr, Mg, Zn, Cu, Mn, and
      Fe), besides toxic metals (Cd, Co, and Pb), were determined using inductively
      coupled plasma atomic emission spectrometry (ICP-OES) and mass spectrometry (ICP
      MS) techniques. The concentration of essential elements was from 1.5- (Zn) to 4.7
      fold (Fe) higher in hair and from 2.4- to 3.3-fold higher in the nails of the
      control group compared to the patients, while the opposite trend was observed for
      the heavy metals. The differences between two groups in the level of metals
      (except for Zn) were statistically significant (p < 0.05). The association of
      cancer with metals and other factors was evaluated using various statistical
      methods, for which the best predictions were obtained using logistic regression,
      artificial neural networks and canonical discriminant analysis. The classifiers
      constructed using the data from a survey of diet and lifestyle, and analysis of
      elements in hair and nails, can be useful tools for estimating cancer risk and
      early screening of the disease. 

PMID- 25616224
TI  - Rhinitis in children: common clinical presentations and differential diagnoses.
AB  - Rhinitis is a common presentation in childhood. Acute virally induced rhinitis is
      generally self-limiting and usually does not require medical attention. Whilst
      allergic rhinitis is the focus of the paediatric allergist, the presentation of
      other diseases or comorbidities that can complicate or mimic allergic rhinitis
      needs to be considered. Effects on the child's quality of life also need to be
      addressed. Rhinitis can be associated with asthma and other significant
      comorbidities: importantly, non-allergic rhinitis can sometimes be a consequence
      of systemic immune impairment. The diagnosis of rhinitis is based on clinical
      findings with directed investigations. Nasal nitric oxide measurement is an
      emerging diagnostic tool and helpful particularly in relation to evaluating the
      differential diagnosis in more difficult rhinitis. Successfully identifying the
      cause of rhinitis in childhood and associated comorbidities can ensure that the
      patient is successfully treated as described in the recently published EAACI
      Pediatric Rhinitis Position Paper. 

PMID- 25616223
TI  - Effects of ambient coarse, fine, and ultrafine particles and their biological
      constituents on systemic biomarkers: a controlled human exposure study.
AB  - BACKGROUND: Ambient coarse, fine, and ultrafine particles have been associated
      with mortality and morbidity. Few studies have compared how various particle size
      fractions affect systemic biomarkers. OBJECTIVES: We examined changes of blood
      and urinary biomarkers following exposures to three particle sizes. METHODS:
      Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse
      (2.5-10 MUm; mean, 213 MUg/m3) and fine (0.15-2.5 MUm; mean, 238 MUg/m3)
      concentrated ambient particles (CAPs), and filtered ambient and/or medical air.
      Twenty-five participants were exposed to ultrafine CAP (< 0.3 MUm; mean, 136
      MUg/m3) and filtered medical air. Exposures lasted 130 min, separated by >= 2
      weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr
      postexposure to determine blood interleukin-6 and C-reactive protein
      (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF;
      vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary
      VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model
      regressions assessed pre- and postexposure differences. RESULTS: One hour
      postexposure, for every 100-MUg/m3 increase, coarse CAP was associated with
      increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O3,
      fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg
      creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with
      increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95%
      CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was
      significantly associated with biomarker changes similar to those found with CAPs.
      CONCLUSIONS: Ambient particles with various sizes/constituents may influence
      systemic biomarkers differently. Endotoxin in ambient particles may contribute to
      vascular mediator changes and oxidative stress.

PMID- 25616225
TI  - The role of dorsomedial hypotalamus ionotropic glutamate receptors in the
      hypertensive and tachycardic responses evoked by Tityustoxin
      intracerebroventricular injection.
AB  - The scorpion envenoming syndrome is an important worldwide public health problem
      due to its high incidence and potential severity of symptoms. Some studies
      address the high sensitivity of the central nervous system to this toxin action.
      It is known that cardiorespiratory manifestations involve the activation of the
      autonomic nervous system. However, the origin of this modulation remains unclear.
      Considering the important participation of the dorsomedial hypotalamus (DMH) in
      the cardiovascular responses during emergencial situations, the aim of this work
      is to investigate the involvement of the DMH on cardiovascular responses induced
      by intracerebroventricular (icv) injection of Tityustoxin (TsTX, a alpha-type
      toxin extracted from the Tityus serrulatus scorpion venom). Urethane
      anaesthetized male Wistar rats (n=30) were treated with PBS, muscimol or
      ionotropic glutamate receptor antagonists, bilaterally in DMH and later, with an
      icv injection of TsTX, or treated only with PBS in both regions. TsTX evoked a
      marked increase in mean arterial pressure and heart rate in all control rats.
      Interestingly, injection of muscimol, a GABAA receptor agonist, did not change
      the pressor and tachycardic responses evoked by TsTX. Remarkably, the injection
      ionotropic glutamate receptors antagonists in DMH abolished the pressor and the
      tachycardic response evoked by TsTX. Our data suggest that the central circuit
      recruited by TsTX, whose activation results in an array of physiological and
      behavioral alterations, depend on the activation of DMH ionotropic glutamate
      receptors. Moreover, our data provide new insights on the central mechanisms
      involved in the development of symptoms in the severe scorpion envenomation
      syndrome. 

PMID- 25616226
TI  - Assessment of ultrafine particles and noise measurements using fuzzy logic and
      data mining techniques.
AB  - This study focuses on correlations between total number concentrations, road
      traffic emissions and noise levels in an urban area in the southwest of Spain
      during the winter and summer of 2009. The high temporal correlation between sound
      pressure levels, traffic intensity, particle number concentrations related to
      traffic, black carbon and NOx concentrations suggests that noise is linked to
      traffic emissions as a main source of pollution in urban areas. First, the
      association of these different variables was studied using PreFuRGe, a
      computational tool based on data mining and fuzzy logic. The results showed a
      clear association between noise levels and road-traffic intensity for non
      extremely high wind speed levels. This behaviour points, therefore, to vehicular
      emissions being the main source of urban noise. An analysis for estimating the
      total number concentration from noise levels is also proposed in the study. The
      high linearity observed between particle number concentrations linked to traffic
      and noise levels with road traffic intensity can be used to calculate traffic
      related particle number concentrations experimentally. At low wind speeds, there
      are increases in noise levels of 1 dB for every 100 vehicles in circulation. This
      is equivalent to 2000 cm(-3) per vehicle in winter and 500 cm(-3) in summer. At
      high wind speeds, wind speed could be taken into account. This methodology allows
      low cost sensors to be used as a proxy for total number concentration monitoring
      in urban air quality networks.

PMID- 25616228
TI  - Inactivation of antibiotic resistance genes in municipal wastewater effluent by
      chlorination and sequential UV/chlorination disinfection.
AB  - This study investigated disinfection methods including chlorination, ultraviolet
      (UV) irradiation and sequential UV/chlorination treatment on the inactivation of
      antibiotic resistance genes (ARGs). ARGs including sul1, tetX, tetG, intI1, and
      16S rRNA genes in municipal wastewater treatment plant (MWTP) effluent were
      examined. The results indicated a positive correlation between the removal of
      ARGs and chlorine dosage (p=0.007-0.014, n=6),as well as contact time (p=0.0001,
      n=10). Greater free chlorine (FC) dosage leads to higher removal for all the
      genes and the maximum removal (1.30-1.49 logs) could be achieved at FC dosage of
      30 mg L(-1). The transformation kinetic data for ARGs removal (log C0/C) followed
      the second-order reaction kinetic model with FC dosage (R(2)=0.6829-0.9999) and
      contact time (R(2)=0.7353-8634), respectively. Higher ammonia nitrogen (NH3-N)
      concentration was found to lead to lower removal of ARGs at the same chlorine
      dosage. When the applied Cl2:NH3-N ratio was over 7.6:1, a significant reduction
      of ARGs (1.20-1.49 logs) was achieved. By using single UV irradiation, the log
      removal values of tetX and 16Ss rRNA genes were 0.58 and 0.60, respectively,
      while other genes were 0.36-0.40 at a fluence of 249.5 mJ cm(-2), which was
      observed to be less effective than chlorination. With sequential UV/chlorination
      treatment, 0.006 to 0.31 log synergy values of target genes were observed under
      different operation parameters.

PMID- 25616227
TI  - Impact of medium-distance pollution sources in a Galician suburban site (NW
      Iberian peninsula).
AB  - This work studies airborne quality in a geographical area that has not been
      investigated broadly: a suburban site nearby A Coruna (Galicia, NW Iberian
      Peninsula). In contrast to major Spanish cities, the site has Atlantic
      characteristics: rainy, scarce calm weather and infrequent prolonged sunny
      periods. The relationships between several gaseous pollutants (NO, NO2, NOx, CO,
      O3, PM10, PM2.5 and PM1) and their temporal trends (daily, monthly and seasonal)
      were evaluated. The aim was to unravel whether medium- and long-distance sources
      were impacting upon the site. Univariate studies focused on factorizing the
      pollutants according to a codifying factor (wind direction, hour of the day,
      season and month). Multivariate studies (Varimax-rotated factorial analysis) were
      done separately on both weekdays and weekends. The intensity of the daily maxima
      for NO, NO2, NOx and CO was lower during the weekends, with O3 behaving opposite.
      PM average values agreed with previous historical reports for a rural background
      station relatively close to the site and they decreased daily between 11:00 and
      19:00 h, likely because of the marine breeze. With moderate wind speeds the
      pollutants were associated to medium-distance pollution sources, mainly the city
      of A Coruna and a combination of industrial pollution sources (a power plant, a
      solid waste incinerator and a regional airport).

PMID- 25616229
TI  - Efficient tritiation of the translocator protein (18 kDa) selective ligand DPA
      714.
AB  - DPA-714 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5
      a]pyrimidin-3-yl)acetamide) is a recently discovered fluorinated ligand of the
      translocator protein 18 kDa (TSPO). Labelled with the short-lived positron
      emitter fluorine-18, this structure is today the radioligand of reference for in
      vivo imaging of microglia activation and neuroinflammatory processes with
      positron emission tomography. In the present work, an isotopically tritium
      labelled version was developed ([(3) H]DPA-714), in order to access high
      resolution in vitro and ex vivo microscopic autoradiography studies, repeated and
      long-lasting receptor binding studies and in vivo pharmacokinetic determination
      at late time points. Briefly, DPA-714 as reference, and its 3,5-dibrominated
      derivative as precursor for labelling, were both prepared from DPA-713 in
      nonoptimized 32% (two steps) and 10% (three steps) yields, respectively.
      Reductive debromination using deuterium gas and Pd/C as catalyst in methanol,
      performed at the micromolar scale, confirmed the regioselective introduction of
      two deuterium atoms at the meta positions of the phenyl ring. Tritiodebromination
      was analogously performed using no-carrier tritium gas. HPLC purification
      provided >96% radiochemically pure [(3) H]DPA-714 (7 GBq) with a 2.1 TBq/mmol
      specific radioactivity. Interestingly, additional hydrogen-for-tritium exchanges
      were also observed at the 5-methyl and 7-methyl positions of the pyrazolo[1,5
      a]pyrimidine, opening novel perspectives in the labelling of compounds featuring
      this heterocyclic core. 

PMID- 25616230
TI  - Tritium labelling of a cholesterol amphiphile designed for cell membrane
      anchoring of proteins.
AB  - Cell membrane association of proteins can be achieved by the addition of lipid
      moieties to the polypeptide chain, and such lipid-modified proteins have
      important biological functions. A class of cell surface proteins contains a
      complex glycosylphosphatidylinositol (GPI) glycolipid at the C-terminus, and they
      are accumulated in cholesterol-rich membrane microdomains, that is, lipid rafts.
      Semisynthetic lipoproteins prepared from recombinant proteins and designed lipids
      are valuable probes and model systems of the membrane-associated proteins.
      Because GPI-anchored proteins can be reinserted into the cell membrane with the
      retention of the biological function, they are appropriate candidates for
      preparing models via reduction of the structural complexity. A synthetic
      headgroup was added to the 3beta-hydroxyl group of cholesterol, an essential
      lipid component of rafts, and the resulting cholesterol derivative was used as a
      simplified GPI mimetic. In order to quantitate the membrane integrated GPI
      mimetic after the exogenous addition to live cells, a tritium labelled
      cholesterol anchor was prepared. The radioactive label was introduced into the
      headgroup, and the radiolabelled GPI mimetic anchor was obtained with a specific
      activity of 1.37 TBq/mmol. The headgroup labelled cholesterol derivative was
      applied to demonstrate the sensitive detection of the cell membrane association
      of the anchor under in vivo conditions. 

PMID- 25616231
TI  - Synthesis of a [(14) C]-steroid intermediate: an application of a nonstabilized
      Horner-Wadsworth-Emmons olefination approach.
AB  - Radiolabeled steroid derivative 1 was successfully prepared using a Horner
      Wadsworth-Emmons approach: a [(14) C]-label was efficiently incorporated into the
      C-18 position of the molecule. Previously published procedures employing other
      olefination methods are either not applicable due to unavailability of [(14) C]
      precursors or suffer from poor reactivity. 

PMID- 25616233
TI  - Prognostic respiratory parameters in heart failure patients with and without
      exercise oscillatory ventilation - a systematic review and descriptive meta
      analysis.
AB  - The purpose of this review was to describe the occurrence of prognostic variables
      as derived from cardiopulmonary exercise testing (CPET) in patients with heart
      failure (HF), presenting exercise oscillatory ventilation (EOV) compared to
      patients without EOV. The effect of EOV on peak oxygen consumption (VO2), minute
      ventilation/carbon dioxide production (VE/VCO2) slope, oxygen uptake efficiency
      slope (OUES), rest and peak pulmonary end-tidal carbon dioxide pressure (PETCO2)
      was meta-analysed. A systematic search strategy was performed in five databases
      (Pubmed, Cochrane Library, PEDro, Science Direct and Web of Science) assessing
      252 articles for eligibility. Nineteen citations met the inclusion criteria
      totalling 3032 patients with HF (EOV=1111; non-EOV=1921). The risk of bias was
      assessed by two researchers. Extracted data were pooled using random or fixed
      effects meta-analysis, if appropriate. The level of significance was set at
      p<=0.05. Overall, the presentation of EOV significantly indicated aggravated
      prognostic markers. Subgroup analysis revealed left ventricular ejection fraction
      (LVEF) and mode of CPET protocol as independent factors, whereas defining EOV
      significantly influenced the results. A meta-analysis of studies reporting hazard
      ratios for cardiovascular events demonstrated that HF patients with EOV run a
      fourfold risk for an adverse event compared to HF patients without EOV. In
      general, these findings suggest that the presence of EOV in patients with HF is
      associated with a deterioration of the prognostic CPET parameters. Furthermore,
      EOV can occur in HF patients with reduced as well as preserved ejection fraction.
      Further research on defining and assessing EOV in a more accurate and
      reproducible way is required. 

PMID- 25616234
TI  - Percutaneous closure of post-myocardial infarction ventricular septal rupture in
      patients with ventricular septal rupture and apical thrombus: first case in
      literature.

PMID- 25616235
TI  - Construction, expression, purification, and characterization of a dual-targeting
      PD-1/VEGF-A fusion protein (P-V).
AB  - Targeting programmed death-1 (PD-1) is regarded as a novel and promising means
      for the treatment of many types of solid tumor. In the tumor microenvironment
      (TME), VEGF expression is dramatically up-regulated, and compounds that
      neutralize VEGF or block the interaction of VEGF with its receptors exhibit
      potent antitumor activity, and blocking PD-1 might promote T cell infiltration
      into TME and significantly enhance local immune activation. Thus, we fused domain
      II and domain III of kinase-insert domain receptor (KDR), the receptor of VEGF-A,
      to the Fc side of an anti-PD-1 monoclonal antibody with a (Gly4Ser)3 linker to
      generate a dual targeting fusion protein. The recombinant plasmid was
      successfully constructed and the fusion protein was expressed in 293E cells.
      Protein purification was performed in a single step by using protein A affinity
      chromatography. The molecular weight of the fusion protein was approximately
      220kDa, and the yield was approximately 2.97g/L. Specific binding of recombinant
      protein to PD-1 and VEGF was detected by enzyme-linked immunosorbent assay
      (ELISA) analysis. Half maximal effective concentration (EC50) values were 0.561nM
      for PD-1 and 0.682nM for VEGF-A; accordingly, half maximal inhibitory
      concentration (IC50) values were 0.914nM and 0.583nM, respectively. Proliferation
      inhibition assays indicated that the fusion protein could inhibit the growth of
      human umbilical vein endothelial cells effectively. Taken together, the results
      indicate that this novel fusion protein can simultaneously target PD-1 and VEGF
      and may be beneficial for combining anti-angiogenesis with immunotherapeutic
      approaches for the treatment of patients with cancer. 

PMID- 25616236
TI  - Metal remediation and biodegradation potential of earthworm species on municipal
      solid waste: a parallel analysis between Metaphire posthuma and Eisenia fetida.
AB  - Information on vermicomposting with Metaphire posthuma is scanty. This paper,
      therefore, aims to evaluate the bioconversion efficiency of this species against
      Eiseniafetida. For comparative analysis, different combinations of municipal
      solid waste (MSW) and cow dung were used as substrates. The contents of total N
      and availability of P, K, and Fe increased significantly in both Metaphire and
      Eisenia systems which was accompanied by substantial reduction in pH and total
      organic C. Both species exhibited similar levels of urease activity and microbial
      respiration. Moreover, bioavailability of heavy metals (Pb, Zn, Mn, and Cu) was
      reduced substantially during vermicomposting, irrespective of the earthworm
      species. In contrast, each species was distinguished by the enhancement either in
      microbial biomass C and phosphatase activity (Eisenia) or in humification and
      fulvic/humic acid C (Metaphire). The overall results suggest that indigenous
      earthworm, M.posthuma could be utilized as a successful candidate for
      bioprocessing of toxic wastes. 

PMID- 25616237
TI  - Effect of different livestock dungs as inoculum on food waste anaerobic digestion
      and its kinetics.
AB  - The aim of this study was to evaluate the effect of different livestock inoculums
      on the anaerobic digestion of food waste (FW). Five different livestock dungs
      i.e., poultry dung (PD), goat dung (GD), cow dung (CD), piggery dung (PGD) and
      rhinoceros dung (RD) were utilized as inoculums and their effects were valued in
      various food to microorganism (F/M) ratios in batch reactors. Different livestock
      dungs achieved higher methane production and volatile solids (VS) reduction in
      different F/M ratios such as PD, GD, CD, PGD and RD achieved at F/M ratio
      maintained at 1.5, 2, 2, 1.5 and 1.5, respectively. The results indicated that CD
      and PGD inoculum were more suitable for the anaerobic digestion of FW than other
      livestock dungs. Reactors inoculated with CD achieved higher methane production
      (227mLg(-1)VS degraded) and volatile solids degradation (54.58%) at F/M ratio
      maintained at 2. 

PMID- 25616238
TI  - Wheat bran biorefinery--an insight into the process chain for the production of
      lactic acid.
AB  - The present study investigates a wheat bran biorefinery including major
      processing steps pre-extraction, pre-treatment and lactic acid fermentation.
      Concerning the dry mass distribution, during the pre-extraction 32% of the
      feedstock was recovered, offering some perspectives for applications in food
      area. The pre-treatment (hydrothermal/enzymatic hydrolysis) of the remaining cake
      solubilized 34% of dry mass and led to a fermentable sugar concentration of
      21g/L. The fermentation resulted in a lactic acid yield of 0.73g/g substrate.
      Concentrating the fermentation feed via nanofiltration did not improve the lactic
      acid productivity. Taking into account that Lactobacillus pentosus, a
      heterofermentative microorganism was used, the dry mass balance revealed a
      product yield of 47% (32% extract, 15% lactic acid). Based on a theoretical
      consideration involving a cellulolytic enzyme production (10% feedstock
      allocation) and lignin utilization, under optimized conditions a maximum product
      yield of around 80% (35% extract, 39% lactic acid, 6% lignin) could be expected. 

PMID- 25616239
TI  - Regulation of starch and lipid accumulation in a microalga Chlorella sorokiniana.
AB  - Microalgae have attracted growing attention due to their potential in biofuel
      feedstock production. However, current understanding of the regulatory mechanisms
      for lipid biosynthesis and storage in microalgae is still limited. This study
      revealed that the microalga Chlorella sorokiniana showed sequential accumulation
      of starch and lipids. When nitrogen was replete and/or depleted over a short
      period, starch was the predominant carbon storage form with basal levels of lipid
      accumulation. After prolonged nitrogen depletion, lipid accumulation increased
      considerably, which was partially due to starch degradation, as well as the
      turnover of primary metabolites. Lipid accumulation is also strongly dependent on
      the linear electron flow of photosynthesis, peaking at lower light intensities.
      Collectively, this study reveals a relatively clear regulation pattern of starch
      and lipid accumulation that is basically controlled by nitrogen levels. The
      mixotrophic growth of C. sorokiniana shows promise for biofuel production in
      terms of lipid accumulation in the final biomass. 

PMID- 25616240
TI  - Pluggable microbial fuel cell stacks for septic wastewater treatment and
      electricity production.
AB  - Septic tanks and other decentralized wastewater treatment systems play an
      important role in protecting public health and water resource for remote or
      developing communities. Current septic systems do not have energy production
      capability, yet such feature can be very valuable for areas lack access to
      electricity. Here we present an easy-to-operate microbial fuel cell (MFC) stack
      that consists a common base and multiple pluggable units, which can be connected
      in either series or parallel for electricity generation during waste treatment in
      septic tanks. Lab studies showed such easy configuration obtained a power density
      of 142+/-6.71mWm(-2) when 3 units are connected in parallel, and preliminary
      calculation indicates that a system that costs approximately US $25 can power a 6
      watt LED light for 4h per day with great improvement potential. Detailed
      electrochemical characterizations provide insights on system internal loss and
      technology advancement needed. 

PMID- 25616241
TI  - MR image reconstruction with block sparsity and iterative support detection.
AB  - This work aims to develop a novel magnetic resonance (MR) image reconstruction
      approach motivated by the recently proposed sampling framework with union-of
      subspaces model (SUoS). Based on SUoS, we propose a mathematical formalism that
      effectively integrates a block sparsity constraint and support information which
      is estimated in an iterative fashion. The resulting optimization problem consists
      of a data fidelity term and a support detection based block sparsity (SDBS)
      promoting term penalizing entries within the complement of the estimated support.
      We provide optional strategies for block assignment, and we also derive unique
      and robust recovery conditions in terms of the structured restricted isometric
      property (RIP), namely the block-RIP. The block-RIP constant we derive is lower
      than that of the previous structured sparse method, which leads to a reduction of
      the measurements. Simulation results for reconstructing individual and multiple
      T1/T2-weighted images demonstrate the consistency with our theoretical claims,
      and show considerable improvement in comparison with methods using only block
      sparsity or support information. 

PMID- 25616242
TI  - Response: Association of subarachnoid hemorrhage and phentermine usage.

PMID- 25616243
TI  - Preparation and application of a novel molecularly imprinted solid-phase
      microextraction monolith for selective enrichment of cholecystokinin
      neuropeptides in human cerebrospinal fluid.
AB  - A novel molecularly imprinted polymer (MIP) monolith for highly selective
      extraction of cholecystokinin (CCK) neuropeptides was prepared in a micropipette
      tip. The MIPs were synthesized by epitope imprinting technique and the
      polymerization conditions were investigated and optimized. The synthesized MIPs
      were characterized by infrared spectroscopy, elemental analyzer and scanning
      electron microscope. A molecularly imprinted solid-phase microextraction (MI-MU
      SPE) method was developed for the extraction of CCK neuropeptides in aqueous
      solutions. The parameters affecting MI-MU-SPE were optimized. The results
      indicated that this MIP monolith exhibited specific recognition capability and
      high enrichment efficiency for CCK neuropeptides. In addition, it showed
      excellent reusability. This MIP monolith was used for desalting and enrichment of
      CCK4, CCK5 and CCK8 from human cerebrospinal fluid prior to matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry analysis, and the results
      show that this MIP monolith can be a useful tool for effective purification and
      highly selective enrichment of multiple homologous CCK neuropeptides in
      cerebrospinal fluid simultaneously. By employing MI-MU-SPE combined with HPLC-ESI
      MS/MS analysis, endogenous CCK4 in human cerebrospinal fluid was quantified.

PMID- 25616244
TI  - More Than Fear Induction: Toward an Understanding of People's Motivation to Be
      Well-Prepared for Emergencies in Flood-Prone Areas.
AB  - This article examines the extent and manner to which evaluations of flood-related
      precautions are affected by an individual's motivation and perception of context.
      It argues that the relationship between risk perception and flood risk
      preparedness can be fruitfully specified in terms of vulnerability and efficacy
      if these concepts are put into the perspective of prevention-focused motivation.
      This relationship was empirically examined in a risk communication experiment in
      a delta area of the Netherlands (n = 1,887). Prevention-focused motivation was
      induced by contextualized risk information. The results showed that prevention
      focused individuals were more sensitive to the relevance of potential precautions
      for satisfying their needs in the context they found themselves in. The needs
      included, but were not limited to, fear reduction. Due to the heterogeneity of
      the residents, the evaluations reflected individual differences in the intensity
      and the selectivity of precautionary processes. Four types of persons could be
      distinguished according to their evaluation of precautionary measures: a high
      scoring minority, two more selective types, and a low-scoring minority. For
      policymakers and risk communicators it is vital to consider the nature of
      prevention motivation and the context in which it is likely to be high. 

PMID- 25616245
TI  - Formation and characterization of hypermineralized zone beneath dentine lesion
      body induced by topical fluoride in-vitro.
AB  - OBJECTIVE: This in-vitro study aimed to evaluate and characterize the
      hypermineralized zone (Hyper-zone) formed beneath the remineralized dentine
      lesion body by transverse microradiography (TMR), scanning electron microscopy
      (SEM) and energy dispersive X-ray analysis (EDS). DESIGN: Demineralized bovine
      dentine specimens were treated with fluoride solutions (APF, NaF) and
      remineralized for 2-4 weeks. Then thin sections were prepared to characterize the
      Hyper-zone by TMR, EDS. Fractured specimen surfaces were observed by SEM.
      RESULTS: TMR analysis revealed a higher mineral density at Hyper-zone than that
      of sound dentine (48vol%) ranging from 50 up to 61vol% and the thickness ranging
      from 197 to 344MUm for 4-week specimens, while specimens without fluoride
      treatment did not show Hyper-zone. SEM pictures at Hyper-zone showed no evident
      crystal-like deposits in dentinal tubules and no notable difference when compared
      to that in sound dentine. EDS analysis demonstrated higher concentrations of Ca
      and P at Hyper-zone than those in sound dentine, which corresponded to the TMR
      profile, while the magnesium (Mg) concentration was low at this zone.
      CONCLUSIONS: Demineralized dentine lesions exposed to fluoride and
      remineralization treatments exhibited Hyper-zone beneath the lesion body, in
      which the mineral density was higher than that of sound dentine. Possible
      mechanism for the formation of Hyper-zone was discussed by assuming removal of
      mineral regulators such as Mg and other organic substances from sound dentine
      during de-/remineralization processes.

PMID- 25616246
TI  - Motor skill failure or flow-experience? Functional brain asymmetry and brain
      connectivity in elite and amateur table tennis players.
AB  - Functional hemispheric asymmetry is assumed to constitute one underlying
      neurophysiological mechanism of flow-experience and skilled psycho-motor
      performance in table tennis athletes. We hypothesized that when initiating motor
      execution during motor imagery, elite table tennis players show higher right-
      than left-hemispheric temporal activity and stronger right temporal-premotor than
      left temporal-premotor theta coherence compared to amateurs. We additionally
      investigated, whether less pronounced left temporal cortical activity is
      associated with more world rank points and more flow-experience. To this aim,
      electroencephalographic data were recorded in 14 experts and 15 amateur table
      tennis players. Subjects watched videos of an opponent serving a ball and were
      instructed to imagine themselves responding with a specific table tennis stroke.
      Alpha asymmetry scores were calculated by subtracting left from right hemispheric
      8-13 Hz alpha power. 4-7 Hz theta coherence was calculated between temporal
      (T3/T4) and premotor (Fz) cortex. Experts showed a significantly stronger shift
      towards lower relative left-temporal brain activity compared to amateurs and a
      significantly stronger right temporal-premotor coherence than amateurs. The shift
      towards lower relative left-temporal brain activity in experts was associated
      with more flow-experience and lower relative left temporal activity was
      correlated with more world rank points. The present findings suggest that skilled
      psycho-motor performance in elite table tennis players reflect less
      desynchronized brain activity at the left hemisphere and more coherent brain
      activity between fronto-temporal and premotor oscillations at the right
      hemisphere. This pattern probably reflect less interference of irrelevant
      communication of verbal-analytical with motor-control mechanisms which implies
      flow-experience and predict world rank in experts.

PMID- 25616247
TI  - Temporal and spatial expression analysis of peripheral myelin protein 22 (Pmp22)
      in developing Xenopus.
AB  - Peripheral myelin protein 22 (Pmp22), a member of the junction protein family
      Claudin/EMP/PMP22, contributes to the formation and maintenance of myelin sheaths
      in the peripheral nervous system. Apart from the establishment and maintenance of
      peripheral nerves, Pmp22 and its family member have also participated in a broad
      range of more general processes including cell cycle regulation and apoptosis
      during development. Pmp22 has been identified from several vertebrate species
      including mouse, human and zebrafish. However, Pmp22 has not been identified from
      Xenopus embryos yet. In this paper, we cloned Pmp22 from Xenopus laevis and
      evaluated its expression during embryogenesis. We found that Pmp22 was initially
      expressed in the mesoderm and cement gland during the neurula stage. At early
      tailbud stage, strong expression of Pmp22 was detected in the trigeminal and
      profundal ganglia as well as developing somites and branchial arches. Later in
      development, Pmp22 was expressed specifically in cranio-facial cartilage, roof
      plate and floor plate of the developing brain, otic vesicle and lens. Pmp22 is
      also strongly expressed in the developing trachea and lungs. Based on its
      expression in facial tissues, we propose that Pmp22 may be involved in the
      formation of head structure in addition to the maintenance of functional
      peripheral nerves in Xenopus embryos.

PMID- 25616248
TI  - Estradiol concentration and the expression of estrogen receptors in the testes of
      the domestic goose (Anser anser f. domestica) during the annual reproductive
      cycle.
AB  - Seasonal fluctuations in the activity of bird testes are regulated by a complex
      mechanism where androgens play a key role. Until recently, the role played by
      estrogens in males has been significantly underestimated. However, there is
      growing evidence that the proper functioning of the testes is associated with
      optimal estradiol (E2) concentration in both the plasma and testes of many
      mammalian species. Estrogens are gradually emerging as very important players in
      hormonal regulation of reproductive processes in male mammals. Despite the
      previously mentioned, it should be noted that estrogenic action is limited by the
      availability of specific receptors--estrogen receptor alpha (ERalpha) and
      estrogen receptor beta (ERbeta). Interestingly, there is a general scarcity of
      information concerning the estrogen responsive system in the testes of male
      birds, which is of particular interest in exploring the phenomenon of seasonality
      of reproduction. To address this question, we have investigated for the first
      time the simultaneous expression of testicular ERalpha and ERbeta genes and
      proteins with the accompanying plasma and testicular E2 concentrations during the
      annual reproductive cycle of male bird. The research model was the domestic goose
      (Anser anser f. domestica), a species whose annual reproductive cycle can be
      divided into 3 distinct phases characterized by changes in testicular activity.
      It has been revealed that the stable plasma E2 profile did not correspond to
      changing intratesticular E2 profile throughout the experiment. The expression of
      ERalpha and ERbeta genes and proteins was detected in gander testes and it
      fluctuated on a seasonal basis with lower level in breeding and sexual
      reactivation stages and higher level during the nonbreeding stage. Our results
      demonstrated changes in testicular sensitivity to estrogens in male domestic
      goose during the annual reproductive cycle. The seasonal pattern of estrogen
      receptors (ERs) expression was analyzed against the hormonal background and a
      potential mechanism of ERs regulation in bird testes was proposed. The present
      study revealed seasonal variations in the estrogen responsive system, but further
      research is needed to fully explore the role of estrogens in the reproductive
      tract of male birds.

PMID- 25616250
TI  - N-methyldiethanolamine: a multifunctional structure-directing agent for the
      synthesis of SAPO and AlPO molecular sieves.
AB  - In the present study, N-methyldiethanolamine (MDEA) is demonstrated to be a
      multifunctional structure-directing agent for the synthesis of aluminophosphate
      based molecular sieves. Four types of molecular sieves, including SAPO-34, -35,
      AlPO-9 and -22, are for the first time acquired with MDEA as a novel template.
      The phase selectivity of the present synthesis is found to be condition
      dependent. SAPO-34 (CHA) crystallizes from a conventional hydrothermal system
      with a higher MDEA concentration. When using MDEA as both the template and
      solvent, pure SAPO-35 (LEV) is obtained from the synthetic gel with a high
      P2O5/Al2O3 ratio of (2-3), in which the concentration of MDEA could be varied in
      a wide range. AlPO-9 and AlPO-22 (AWW) are synthesized under the similar
      conditions to SAPO-35, except without the addition of Si source. The
      physicochemical properties of the obtained samples are investigated by XRD, XRF,
      SEM, N2 physisorption, TG-DSC, and various NMR spectra ((13)C, (29)Si, (27)Al and
      (31)P). Both SAPO-34 and SAPO-35 show good thermal stability, large surface area,
      and high pore volume. The catalytic performance of SAPO-34 is evaluated by the
      methanol-to-olefins (MTO) reaction and a good (C2H4+C3H6) selectivity of 82.7%
      has been achieved. 

PMID- 25616249
TI  - Chemoselective detection and discrimination of carbonyl-containing compounds in
      metabolite mixtures by 1H-detected 15N nuclear magnetic resonance.
AB  - NMR spectra of mixtures of metabolites extracted from cells or tissues are
      extremely complex, reflecting the large number of compounds that are present over
      a wide range of concentrations. Although multidimensional NMR can greatly improve
      resolution as well as improve reliability of compound assignments, lower
      abundance metabolites often remain hidden. We have developed a carbonyl-selective
      aminooxy probe that specifically reacts with free keto and aldehyde functions,
      but not carboxylates. By incorporating (15)N in the aminooxy functional group,
      (15)N-edited NMR was used to select exclusively those metabolites that contain a
      free carbonyl function while all other metabolites are rejected. Here, we
      demonstrate that the chemical shifts of the aminooxy adducts of ketones and
      aldehydes are very different, which can be used to discriminate between aldoses
      and ketoses, for example. Utilizing the 2-bond or 3-bond (15)N-(1)H couplings,
      the (15)N-edited NMR analysis was optimized first with authentic standards and
      then applied to an extract of the lung adenocarcinoma cell line A549. More than
      30 carbonyl-containing compounds at NMR-detectable levels, six of which we have
      assigned by reference to our database. As the aminooxy probe contains a
      permanently charged quaternary ammonium group, the adducts are also optimized for
      detection by mass spectrometry. Thus, this sample preparation technique provides
      a better link between the two structural determination tools, thereby paving the
      way to faster and more reliable identification of both known and unknown
      metabolites directly in crude biological extracts.

PMID- 25616251
TI  - Encapsulation of multiple large spherical silica nanoparticles in hollow
      spherical silica shells.
AB  - Here we present the results of a stepwise synthesis of multiple large silica
      nanoparticles encapsulated in hollow, micron sized silica shells for future
      display applications. In the first step, 200-nm diameter silica nanoparticles
      were modified with 3-(trimethoxysilyl) propylmethacrylate (MPS) coupling agent.
      These nanoparticles were then embedded in micron-sized polystyrene particles
      synthesized through dispersion polymerization. To form silica shells on the
      polymer composite particles, tetraethylorthosilicate (TEOS) was added with
      cetyltrimethylammonium bromide (CTAB) surfactant. These three steps resulted in
      the formation of silica shell-covered solid polystyrene particles, each
      containing multiple silica nanoparticles. In the last step, polystyrene content
      was removed via calcination to achieve a multiple-silica-core-in-hollow-silica
      shell composite structure. Dynamic light scattering (DLS) analysis and
      transmission electron microscopy (TEM) confirmed the core/shell morphology of the
      composite structure. 

PMID- 25616252
TI  - Micellar and biochemical properties of a propyl-ended fluorinated surfactant
      designed for membrane-protein study.
AB  - Our goal is to design optimised fluorinated surfactants for handling membrane
      proteins in solution. We report herein the self-assembling and biochemical
      properties of a new hemifluorinated surfactant (H3F6H3DigluM) with a branched
      diglucosylated polar head group and an apolar tail consisting of a
      perfluorohexane core decorated with a hydrogenated propyl tip. For the sake of
      comparison, its fluorinated analogue without propyl tip (F6H3DigluM) was also
      studied. Isothermal titration calorimetry and surface tension showed that the
      addition of a propyl tip has a significant effect on the overall hydrophobicity
      of the surfactant, in contrast to the behaviour described when adding an ethyl
      tip to a fluorinated surfactant. From dynamic light scattering, analytical
      ultracentrifugation and small-angle X-ray scattering, both H3F6H3DigluM and
      F6H3DigluM self-assemble into small globular micelles of 5-7 nm in diameter and
      have aggregation numbers of 62+/-8 and 46+/-2, respectively. Finally,
      H3F6H3DigluM was found to be the best fluorinated surfactant developed in our
      group to stabilise the model membrane protein bacteriorhodopsin (bR) in aqueous
      solution. This study demonstrates the suitability of this new propyl-ended
      fluorinated surfactant for biochemical and structural applications and confirms
      the superiority of hemifluorinated chains over fluorinated ones.

PMID- 25616254
TI  - Individualized assessment of preterm birth risk using two modified prediction
      models.
AB  - OBJECTIVES: To construct two prediction models for individualized assessment of
      preterm delivery risk within 48h and before completed 32 weeks of gestation and
      to test the validity of modified and previously published models. STUDY DESIGN:
      Data on 617 consecutive women with preterm labor transferred to a tertiary care
      center for threatened preterm delivery between 22 and 32 weeks of gestation were
      analysed. Variables predicting the risk of delivery within 48h and before
      completed 32 weeks of gestation were assessed and applied to previously published
      prediction models. Multivariate analyses identified variables that were
      incorporated into two modified models that were subsequently validated. RESULTS:
      Two modified prediction models were developed and internally validated,
      incorporating four and six of the following variables to predict the risk of
      delivery within 48h and before completed 32 weeks of gestation, respectively:
      presence of preterm premature rupture of membranes and/or vaginal bleeding,
      sonographic cervical length, week of gestation, fetal fibronectin, and serum C
      reactive protein. The correspondence between the actual and the predicted preterm
      birth rates suggests excellent calibration of the models. Internal validation
      analyses for the modified 48h and 32 week prediction models revealed considerably
      high concordance-indices of 0.8 (95%CI: [0.70-0.81]) and 0.85 (95%CI: [0.82
      0.90]), respectively. CONCLUSIONS: Two modified prediction models to assess the
      risk of preterm birth were constructed and validated. The models can be used for
      individualized prediction of preterm birth and allow more accurate risk
      assessment than based upon a single risk factor. An online-based risk-calculator
      was constructed and can be assessed through:
      http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/clinical
      software/prematurebirth/.

PMID- 25616253
TI  - Attention deficit/hyperactivity disorder and childhood autism in association with
      prenatal exposure to perfluoroalkyl substances: a nested case-control study in
      the Danish National Birth Cohort.
AB  - BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent pollutants found to
      be endocrine disruptive and neurotoxic in animals. Positive correlations between
      PFASs and neurobehavioral problems in children were reported in cross-sectional
      data, but findings from prospective studies are limited. OBJECTIVES: We
      investigated whether prenatal exposure to PFASs is associated with attention
      deficit/hyperactivity disorder (ADHD) or childhood autism in children. METHODS:
      Among 83,389 mother-child pairs enrolled in the Danish National Birth Cohort
      during 1996-2002, we identified 890 ADHD cases and 301 childhood autism cases
      from the Danish National Hospital Registry and the Danish Psychiatric Central
      Registry. From this cohort, we randomly selected 220 cases each of ADHD and
      autism, and we also randomly selected 550 controls frequency matched by child's
      sex. Sixteen PFASs were measured in maternal plasma collected in early or mid
      pregnancy. We calculated risk ratios (RRs) using generalized linear models,
      taking into account sampling weights. RESULTS: Perfluorooctane sulfonate (PFOS)
      and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs
      were quantified in >= 90% of the samples. We did not find consistent evidence of
      associations between mother's PFAS plasma levels and ADHD [per natural log
      nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR =
      0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter
      increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73,
      1.31)]. We found positive as well as negative associations between higher PFAS
      quartiles and ADHD in models that simultaneously adjusted for all PFASs, but
      these estimates were imprecise. CONCLUSIONS: In this study we found no consistent
      evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or
      childhood autism in children.

PMID- 25616255
TI  - Transcriptome analysis of Burkholderia pseudomallei T6SS identifies Hcp1 as a
      potential serodiagnostic marker.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is able to survive
      extreme environments and utilizes various virulence factors for survival and
      pathogenicity. To compete and survive within these different ecological niches,
      B. pseudomallei has evolved specialized pathways, including the Type VI secretion
      systems (T6SSs), that have a role in pathogenesis as well as interbacterial
      interactions. We examined the expression profile of B. pseudomallei T6SS six gene
      clusters during infection of U937 macrophage cells. T6SS-5 was robustly
      transcribed while the other five clusters were not significantly regulated
      proposing the utility of T6SS-5 as a potential biomarker of exposure to B.
      pseudomallei. Transcription of T6SS regulators VirAG and BprB was also not
      significant during infection when compared to bacteria grown in culture. Guided
      by these findings, three highly expressed T6SS genes, tssJ-4, hcp1 and tssE-5,
      were expressed as recombinant proteins and screened against melioidosis patient
      sera by western analysis and ELISA. Only Hcp1 was reactive by both types of
      analysis. The recombinant Hcp1 protein was further evaluated against a cohort of
      melioidosis patients (n = 32) and non-melioidosis individuals (n = 20) sera and
      the data clearly indicates a higher sensitivity (93.7%) and specificity (100%)
      for Hcp1 compared to bacterial lysate. The detection of anti-Hcp1 antibodies in
      patients' sera indicating the presence of B. pseudomallei highlights the
      potential of Hcp1 to be further developed as a serodiagnostic marker for
      melioidosis.

PMID- 25616256
TI  - DisA and c-di-AMP act at the intersection between DNA-damage response and stress
      homeostasis in exponentially growing Bacillus subtilis cells.
AB  - Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA,
      which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that
      degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to
      elicit repair of DNA damage generated by alkyl groups and H2O2, respectively,
      during vegetative growth. disA forms an operon with radA (also termed sms) that
      encodes a protein distantly related to RecA. Among different DNA damage agents
      tested, only methyl methane sulfonate (MMS) affected disA null strain viability,
      while radA showed sensitivity to all of them. A strain lacking both disA and radA
      was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di
      AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to
      repair DNA damage caused by MMS and in less extent by H2O2, while high levels of
      c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate
      cyclase, CdaS) increased cell survival. Taken together, our results support the
      idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with
      DisA and CdaA contributing to modulate different DNA damage responses during
      exponential growth. 

PMID- 25616257
TI  - A versatile new tool to quantify abasic sites in DNA and inhibit base excision
      repair.
AB  - A number of endogenous and exogenous agents, and cellular processes create abasic
      (AP) sites in DNA. If unrepaired, AP sites cause mutations, strand breaks and
      cell death. Aldehyde-reactive agent methoxyamine reacts with AP sites and blocks
      their repair. Another alkoxyamine, ARP, tags AP sites with a biotin and is used
      to quantify these sites. We have combined both these abilities into one
      alkoxyamine, AA3, which reacts with AP sites with a better pH profile and
      reactivity than ARP. Additionally, AA3 contains an alkyne functionality for
      bioorthogonal click chemistry that can be used to link a wide variety of
      biochemical tags to AP sites. We used click chemistry to tag AP sites with biotin
      and a fluorescent molecule without the use of proteins or enzymes. AA3 has a
      better reactivity profile than ARP and gives much higher product yields at
      physiological pH than ARP. It is simpler to use than ARP and its use results in
      lower background and greater sensitivity for AP site detection. We also show that
      AA3 inhibits the first enzyme in the repair of abasic sites, APE-1, to about the
      same extent as methoxyamine. Furthermore, AA3 enhances the ability of an
      alkylating agent, methylmethane sulfonate, to kill human cells and is more
      effective in such combination chemotherapy than methoxyamine. 

PMID- 25616259
TI  - Developmental exposure to a commercial PBDE mixture: effects on protein networks
      in the cerebellum and hippocampus of rats.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are structurally similar to
      polychlorinated biphenyls (PCBs) and have both central (learning and memory
      deficits) and peripheral (motor dysfunction) neurotoxic effects at
      concentrations/doses similar to those of PCBs. The cellular and molecular
      mechanisms for these neurotoxic effects are not fully understood; however,
      several studies have shown that PBDEs affect thyroid hormones, cause oxidative
      stress, and disrupt Ca2+-mediated signal transduction. Changes in these signal
      transduction pathways can lead to differential gene regulation with subsequent
      changes in protein expression, which can affect the development and function of
      the nervous system. OBJECTIVE: In this study, we examined the protein expression
      profiles in the rat cerebellum and hippocampus following developmental exposure
      to a commercial PBDE mixture, DE-71. METHODS: Pregnant Long-Evans rats were dosed
      perinatally with 0 or 30.6 mg/kg/day of DE-71 from gestation day 6 through
      sampling on postnatal day 14. Proteins from the cerebellum and hippocampus were
      extracted, expression differences were detected by two-dimensional difference gel
      electrophoresis, and proteins were identified by tandem mass spectrometry.
      Protein network interaction analysis was performed using Ingenuity(r) Pathway
      Analysis, and the proteins of interest were validated by Western blotting.
      RESULTS: Four proteins were significantly differentially expressed in the
      cerebellum following DE-71 exposure, whereas 70 proteins were significantly
      differentially expressed in the hippocampus. Of these proteins, 4 from the
      cerebellum and 47 from the hippocampus, identifiable by mass spectrometry, were
      found to have roles in mitochondrial energy metabolism, oxidative stress,
      apoptosis, calcium signaling, and growth of the nervous system. CONCLUSIONS:
      Results suggest that changes in energy metabolism and processes related to
      neuroplasticity and growth may be involved in the developmental neurotoxicity of
      PBDEs.

PMID- 25616258
TI  - MicroRNAs as potential signatures of environmental exposure or effect: a
      systematic review.
AB  - BACKGROUND: The exposome encompasses all life-course environmental exposures from
      the prenatal period onward that influence health. MicroRNAs (miRNAs) are
      interesting entities within this concept as markers and causation of disease.
      MicroRNAs are short oligonucleotide sequences that can interact with several mRNA
      targets. OBJECTIVES: We reviewed the current state of the field on the potential
      of using miRNAs as biomarkers for environmental exposure. We investigated miRNA
      signatures in response to all types of environmental exposure to which a human
      can be exposed, including cigarette smoke, air pollution, nanoparticles, and
      diverse chemicals; and we examined the health conditions for which the identified
      miRNAs have been reported (i.e., cardiovascular disease, cancer, and diabetes).
      METHODS: We searched the PubMed and ScienceDirect databases to identify relevant
      studies. RESULTS: For all exposures incorporated in this review, 27 miRNAs were
      differentially expressed in at least two independent studies. miRNAs that had
      expression alterations associated with smoking observed in multiple studies are
      miR-21, miR-34b, miR-125b, miR-146a, miR-223, and miR-340; and those miRNAs that
      were observed in multiple air pollution studies are miR-9, miR-10b, miR-21, miR
      128, miR-143, miR-155, miR-222, miR-223, and miR-338. We found little overlap
      among in vitro, in vivo, and human studies between miRNAs and exposure. Here, we
      report on disease associations for those miRNAs identified in multiple studies on
      exposure. CONCLUSIONS: miRNA changes may be sensitive indicators of the effects
      of acute and chronic environmental exposure. Therefore, miRNAs are valuable novel
      biomarkers for exposure. Further studies should elucidate the role of the
      mediation effect of miRNA between exposures and effect through all stages of life
      to provide a more accurate assessment of the consequences of miRNA changes.

PMID- 25616260
TI  - Effects of atrazine on estrogen receptor alpha- and G protein-coupled receptor 30
      mediated signaling and proliferation in cancer cells and cancer-associated
      fibroblasts.
AB  - BACKGROUND: The pesticide atrazine does not bind to or activate the classical
      estrogen receptor (ER), but it up-regulates the aromatase activity in estrogen
      sensitive tumor cells. The G protein estrogen receptor (GPR30/GPER) has been
      reported to be involved in certain biological responses to endogenous estrogens
      and environmental compounds exerting estrogen-like activity. OBJECTIVES: We aimed
      to evaluate the potential of atrazine to trigger GPER-mediated signaling in
      cancer cells and cancer-associated fibroblasts (CAFs). METHODS AND RESULTS: Using
      gene reporter assays in diverse types of cancer cells, we found that atrazine did
      not transactivate endogenous ERalpha or chimeric proteins that encode the ERalpha
      and ERbeta hormone binding domains. Conversely, atrazine was able to bind to GPER
      to induce ERK activation and the expression of estrogen target genes, which,
      interestingly, appeared to rely on both GPER and ERalpha expression. As a
      biological counterpart, atrazine stimulated the proliferation of ovarian cancer
      cells that depend on GPER and ERalpha, as evidenced by gene silencing experiments
      and the use of specific signaling inhibitors. Of note, through GPER, atrazine
      elicited ERK phosphorylation, gene expression, and migration in CAFs, thus
      extending its stimulatory role to these main players of the tumor
      microenvironment. CONCLUSIONS: Our results suggest a novel mechanism through
      which atrazine may exert relevant biological effects in cancer cells and CAFs. On
      the basis of our data, atrazine should be included among the environmental
      contaminants that may elicit estrogenic activity through GPER-mediated signaling.

PMID- 25616261
TI  - State of the ART: emerging genetic technologies in reproductive medicine are
      rapidly making real what once was science fiction-are we ready for it?

PMID- 25616262
TI  - The birds, the bees, and technology: four active research areas are boosting
      birth rates.

PMID- 25616263
TI  - Babies from skin cells?: New assisted reproductive technologies are turning
      science fiction into reality.

PMID- 25616264
TI  - Frontiers in male contraception: there are few alternatives now, but several
      promising avenues of research are under way.

PMID- 25616265
TI  - Maternal health in developing countries: engineering approaches and future
      outlook.

PMID- 25616266
TI  - Journey of a thousand miles: harnessing mobile communications technology to solve
      problems in maternal health and child mortality in Balochistan, Pakistan.

PMID- 25616267
TI  - Twisted lines: artificial muscle and advanced instruments can be formed from
      nylon threads and fabric.

PMID- 25616268
TI  - CT differentiation of enlarged mediastinal lymph node due to anthracosis from
      metastatic lymphadenopathy: a comparative study proven by endobronchial US-guided
      transbronchial needle aspiration.
AB  - PURPOSE: Anthracosis often results in mediastinal nodal enlargement. The aim of
      this comparative study was to evaluate if it is possible to differentiate
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)
      proven anthracotic lymph nodes from malignant lymph node enlargement by means of
      multislice computed tomography (MSCT). METHODS: We compared the MSCT findings of
      89 enlarged lymph nodes due to anthracosis with 54 malignant lymph nodes (non
      small cell lung cancer 75.9%, small cell lung cancer 18.5%, and non-Hodgkin
      lymphoma 5.6%). The lymph nodes were assessed for density (calcification, fat,
      and necrosis), shape (oval, round), contrast enhancement, and contour (sharp, ill
      defined). RESULTS: Malignant lymph nodes showed significantly greater axis
      diameters (P < 0.001). Both anthracotic and malignant nodes were most often oval
      (86.5% of all malignant nodes vs. 81.5% of all anthracotic nodes, P = 0.420) and
      showed confluence in a remarkable percentage (28.1% vs. 42.6%, P = 0.075).
      Anthracotic nodes showed calcifications more often (18% vs. 0%, P < 0.001).
      Malignant lymph nodes showed a significantly greater short and long axis diameter
      (P < 0.001), and they had a higher frequency of ill-defined contours (27.8% vs.
      2.2%, P < 0.001) and contrast enhancement (27.8% vs. 5.6%, P < 0.001). Nodal
      necrosis, which appeared in one third of the malignant nodes, was not observed in
      anthracosis (35.2% vs. 0%, P < 0.001). Confluence of enlarged lymph nodes was
      seen in malignant lymph nodes (42.6%), as well as in lymph node enlargement due
      to anthracosis (28.1%, P = 0.075). CONCLUSION: Our results show that there are
      significant differences in MSCT findings of malignant enlarged lymph nodes and
      benign lymph node enlargement due to anthracosis.

PMID- 25616269
TI  - Endovascular intervention for management of pancreatitis-related bleeding: a
      retrospective analysis of thirty-seven patients at a single institution.
AB  - PURPOSE: The aim of this study was to assess the outcome of endovascular
      intervention for pancreatitis-related hemorrhage at a single institution.
      METHODS: From January 2000 to October 2012, thirty-seven patients underwent
      endovascular intervention for the management of pancreatitis-related hemorrhage.
      The underlying etiology of the disease, clinical symptoms and laboratory
      findings, abnormalities seen on computed tomography, and details regarding the
      endovascular procedures were assessed, as were the outcome of each procedure and
      procedure-related complications. RESULTS: A total of 41 endovascular procedures
      were performed in 37 patients. The splenic artery (34.8%) was the most commonly
      treated artery, and pseudoaneurysm was the most commonly detected abnormality on
      digital subtraction angiography (78.3%). Transcatheter embolization was performed
      in the majority of patients (95.1%), while two patients were treated with stent
      grafts. Successful hemostasis without rebleeding was achieved in 34 patients
      (91.9%). Two cases of rebleeding were successfully treated by reintervention.
      Focal splenic infarction, which developed in eight patients, was either
      asymptomatic or accompanied by mild, transient fever. Splenic abscess was the
      only major complication occurring in three patients. Two of these patients died
      from resulting sepsis, while the third recovered after antibiotic treatment.
      CONCLUSION: Endovascular management is effective for achieving hemostasis in
      patients with pancreatitis-related bleeding and demonstrates low recurrence and
      mortality rates.

PMID- 25616270
TI  - Contribution of real-time elastography in diagnosis of polycystic ovary syndrome.
AB  - PURPOSE: We aimed to assess the feasibility and reproducibility of real-time
      elastography (RTE) for displaying the effects of morphological changes in the
      ovary in polycystic ovary syndrome (PCOS). METHODS: Forty-eight patients
      diagnosed with PCOS and 48 healthy women were enrolled in the study.
      Ultrasonography and RTE were performed on the 3rd day of the menstrual cycle.
      Evaluations were performed independently by two radiologists. Ovarian volume,
      number of follicles, elasticity pattern, and strain ratio were measured.
      Elasticity patterns were assessed as hard (type 1; blue or blue-green), moderate
      (type 2; green or green-yellow) or soft (type 3; red or orange-red). RESULTS:
      Both radiologists determined the elasticity pattern as mostly type 1 in the PCOS
      group and type 3 in the control group (P < 0.01). The mean strain ratios obtained
      by the first and second radiologist were 6.1+/-1.8 (2.7-10.1) and 6.0+/-1.5 (3.0
      9.0) in PCOS and 3.3+/-1.2 (1.7-7.2) and 3.2+/-0.9 (1.7-6.8) in the control
      group, respectively (P < 0.001). Interobserver agreement was moderate for the
      elasticity pattern (kappa=0.48) and good for the strain ratio (intraclass
      correlation coefficient, 0.77). A strain ratio of 3.8 was determined as the
      optimized cutoff point by receiver operating curve analysis. Strain ratio was
      correlated with the ovarian volume and the number of detected follicles (P <
      0.001). CONCLUSION: Elasticity pattern and strain ratio can help identify
      morphological changes that make PCOS ovaries stiffer than normal ovaries.

PMID- 25616271
TI  - Accessory hepatic vein recanalization for treatment of Budd-Chiari syndrome due
      to long-segment obstruction of the hepatic vein: initial clinical experience.
AB  - PURPOSE: We aimed to investigate the feasibility and effectiveness of accessory
      hepatic vein recanalization (balloon dilatation/stent insertion) for patients
      with Budd-Chiari syndrome (BCS) due to long-segment obstruction of the hepatic
      vein. METHODS: From March 2010 to December 2013, 20 consecutive patients with
      BCS, due to long-segment obstruction of three hepatic veins, treated with
      accessory hepatic vein recanalization (11 males, 9 females; mean age, 33.4+/-10.9
      years; range, 22-56 years) were included in this retrospective study. Data on
      technical success, clinical success, and follow-up were collected and analyzed.
      RESULTS: Technical and clinical success was achieved in all patients. Each
      patient was managed with a single accessory hepatic vein recanalization
      procedure. No procedure-related complications occurred. The diameter of the
      accessory hepatic vein was 8.45+/-1.47 mm (6-11 mm) at the stem, and there were
      many collateral circulations between the hepatic vein and the accessory hepatic
      vein. The mean pressure of accessory hepatic vein decreased from 47.50+/-5.59 cm
      H2O before treatment to 28.80+/-3.47 cm H2O after treatment (P < 0.001). Abnormal
      levels of total bilirubin, albumin, aspartate aminotransferase, and alanine
      transaminase improved after the treatment. During the follow-up, three patients
      experienced restenosis or stenting of the accessory hepatic vein. CONCLUSIONS: In
      BCS due to long-segment obstruction of the hepatic veins, it is important to
      confirm whether there is a compensatory accessory hepatic vein. For patients with
      a compensatory but obstructed accessory hepatic vein, recanalization is a simple,
      safe, and effective treatment option.

PMID- 25616272
TI  - Virtual patients on the semantic Web: a proof-of-application study.
AB  - BACKGROUND: Virtual patients are interactive computer simulations that are
      increasingly used as learning activities in modern health care education,
      especially in teaching clinical decision making. A key challenge is how to
      retrieve and repurpose virtual patients as unique types of educational resources
      between different platforms because of the lack of standardized content
      retrieving and repurposing mechanisms. Semantic Web technologies provide the
      capability, through structured information, for easy retrieval, reuse,
      repurposing, and exchange of virtual patients between different systems.
      OBJECTIVE: An attempt to address this challenge has been made through the
      mEducator Best Practice Network, which provisioned frameworks for the discovery,
      retrieval, sharing, and reuse of medical educational resources. We have extended
      the OpenLabyrinth virtual patient authoring and deployment platform to facilitate
      the repurposing and retrieval of existing virtual patient material. METHODS: A
      standalone Web distribution and Web interface, which contains an extension for
      the OpenLabyrinth virtual patient authoring system, was implemented. This
      extension was designed to semantically annotate virtual patients to facilitate
      intelligent searches, complex queries, and easy exchange between institutions.
      The OpenLabyrinth extension enables OpenLabyrinth authors to integrate and share
      virtual patient case metadata within the mEducator3.0 network. Evaluation
      included 3 successive steps: (1) expert reviews; (2) evaluation of the ability of
      health care professionals and medical students to create, share, and exchange
      virtual patients through specific scenarios in extended OpenLabyrinth (OLabX);
      and (3) evaluation of the repurposed learning objects that emerged from the
      procedure. RESULTS: We evaluated 30 repurposed virtual patient cases. The
      evaluation, with a total of 98 participants, demonstrated the system's main
      strength: the core repurposing capacity. The extensive metadata schema
      presentation facilitated user exploration and filtering of resources. Usability
      weaknesses were primarily related to standard computer applications' ease of use
      provisions. Most evaluators provided positive feedback regarding educational
      experiences on both content and system usability. Evaluation results replicated
      across several independent evaluation events. CONCLUSIONS: The OpenLabyrinth
      extension, as part of the semantic mEducator3.0 approach, is a virtual patient
      sharing approach that builds on a collection of Semantic Web services and
      federates existing sources of clinical and educational data. It is an effective
      sharing tool for virtual patients and has been merged into the next version of
      the app (OpenLabyrinth 3.3). Such tool extensions may enhance the medical
      education arsenal with capacities of creating simulation/game-based learning
      episodes, massive open online courses, curricular transformations, and a future
      robust infrastructure for enabling mobile learning.

PMID- 25616273
TI  - Patient-reported outcomes and therapeutic affordances of social media: findings
      from a global online survey of people with chronic pain.
AB  - BACKGROUND: Patient-reported outcomes (PROs) from social media use in chronic
      disease management continue to emerge. While many published articles suggest the
      potential for social media is positive, there is a lack of robust examination
      into mediating mechanisms that might help explain social media's therapeutic
      value. This study presents findings from a global online survey of people with
      chronic pain (PWCP) to better understand how they use social media as part of
      self-management. OBJECTIVE: Our aim is to improve understanding of the various
      health outcomes reported by PWCP by paying close attention to therapeutic
      affordances of social media. We wish to examine if demographics of participants
      underpin health outcomes and whether the concept of therapeutic affordances
      explains links between social media use and PROs. The goal is for this to help
      tailor future recommendations for use of social media to meet individuals' health
      needs and improve clinical practice of social media use. METHODS: A total of 231
      PWCP took part in a global online survey investigating PROs from social media
      use. Recruited through various chronic disease entities and social networks,
      participants provided information on demographics, health/pain status, social
      media use, therapeutic affordances, and PROs from use. Quantitative analysis was
      performed on the data using descriptive statistics, cross-tabulation, and cluster
      analysis. RESULTS: The total dataset represented 218 completed surveys. The
      majority of participants were university educated (67.0%, 146/218) and female
      (83.9%, 183/218). More than half (58.7%, 128/218) were married/partnered and not
      working for pay (75.9%, 88/116 of these due to ill health). Fibromyalgia (46.6%,
      55/118) and arthritis (27.1%, 32/118) were the most commonly reported conditions
      causing pain. Participants showed a clear affinity for social network site use
      (90.0%, 189/210), followed by discussion forums and blogs. PROs were consistent,
      suggesting that social media positively impact psychological, social, and
      cognitive health. Analysis also highlighted two strong correlations linking
      platform used and health outcomes (particularly psychological, social, and
      cognitive) to (1) the narrative affordance of social media and (2) frequency of
      use of the platforms. CONCLUSIONS: Results did not uncover definitive
      demographics or characteristics of PWCP for which health outcomes are impacted.
      However, findings corroborate literature within this domain suggesting that there
      is a typical profile of people who use social media for health and that social
      media are more suited to particular health outcomes. Exploration of the
      relationship between social media's therapeutic affordances and health outcomes,
      in particular the narration affordance, warrants further attention by patients
      and clinicians.

PMID- 25616274
TI  - Diet app use by sports dietitians: a survey in five countries.
AB  - BACKGROUND: Despite the hundreds of diet apps available for use on smartphones
      (mobile phones), no studies have examined their use as tools for dietary
      assessment and tracking in sports nutrition. OBJECTIVE: The aim is to examine the
      prevalence and perceptions of using smartphone diet apps for dietary assessment
      and tracking among sports dietitians. METHODS: A cross-sectional online survey to
      examine the use and perception of diet apps was developed and distributed to
      sports dietitians in Australia, Canada, New Zealand, the United Kingdom, and the
      United States (US). RESULTS: The overall response rate from the 1709 sports
      dietitians invited to participate was 10.3% (n=180). diet apps were used by 32.4%
      (57/176) of sports dietitians to assess and track the dietary intake of athletes.
      Sports dietitians from the US were more likely to use smartphone diet apps than
      sports dietitians from other countries (OR=5.61, 95% CI 1.84-17.08, P=.002).
      Sports dietitians used 28 different diet apps, with 56% (32/57) choosing
      MyFitnessPal. Overall, sports dietitians held a positive perception of smartphone
      diet apps, with the majority of respondents viewing diet apps as "better" (25/53,
      47%) or "equivalent" (22/53, 41%) when compared with traditional dietary
      assessment methods. CONCLUSIONS: Nearly one-third of sports dietitians used
      mobile phone diet apps in sports nutrition practice, and viewed them as useful in
      helping to assess and track the dietary intake of athletes.

PMID- 25616275
TI  - Going gently into that good night: what is the best death?

PMID- 25616276
TI  - Colonisation with multidrug-resistant bacteria is associated with increased
      mortality in patients with cirrhosis.

PMID- 25616277
TI  - Elevated glucose-6-phosphate dehydrogenase expression in the cervical cancer
      cases is associated with the cancerigenic event of high-risk human
      papillomaviruses.
AB  - The most important etiologic agent in the pathogenesis of cervical cancers (CCs)
      is human papillomavirus (HPV), while the mechanisms underlying are still not well
      known. Glucose-6-phosphate dehydrogenase (G6PD) is reported to elevate in various
      tumor cells. However, no available references elucidated the correlation between
      the levels of G6PD and HPV-infected CC until now. In the present study, we
      explored the possible role of G6PD in the pathology of CC induced by HPV
      infection. Totally 48 patients with HPV + CC and another 63 healthy women
      enrolled in the clinical were employed in the present study. Overall, prevalence
      of cervical infection with high-risk-HPV (HR-HPV) type examined was HPV-16,
      followed by HPV-18. The expressions of G6PD in CC samples were also detected by
      immunohistochemistry (IHC), qRT-PCR, and Western blot. Regression analysis showed
      elevated G6PD level was positively correlated with the CC development in 30-40
      aged patients with HR-HPV-16/18 infection. The HPV16 + Siha, HPV18 + Hela, and
      HPV-C33A cell lines were employed and transfected with G6PD deficient vectors
      developed in vitro. MTT and flow cytometry were also employed to determine the
      survival and apoptosis of CC cells after G6PD expressional inhibition. Our data
      revealed that G6PD down-regulation induced poor proliferation and more apoptosis
      of HPV18 + Hela cells, when compared with that of HPV16 + Siha and HPV-C33A
      cells. These findings suggest that G6PD expressions in the HR-HPV + human CC
      tissues and cell lines play an important role in tumor growth and proliferation. 

PMID- 25616278
TI  - Serum proteomes distinguish children developing type 1 diabetes in a cohort with
      HLA-conferred susceptibility.
AB  - We determined longitudinal serum proteomics profiles from children with HLA
      conferred diabetes susceptibility to identify changes that could be detected
      before seroconversion and positivity for disease-associated autoantibodies.
      Comparisons were made between children who seroconverted and progressed to type 1
      diabetes (progressors) and those who remained autoantibody negative, matched by
      age, sex, sample periodicity, and risk group. The samples represented the
      prediabetic period and ranged from the age of 3 months to 12 years. After
      immunoaffinity depletion of the most abundant serum proteins, isobaric tags for
      relative and absolute quantification were used for sample labeling. Quantitative
      proteomic profiles were then measured for 13 case-control pairs by high
      performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Additionally, a label-free LC-MS/MS approach was used to analyze depleted sera
      from six case-control pairs. Importantly, differences in abundance of a set of
      proteins were consistently detected before the appearance of autoantibodies in
      the progressors. Based on top-scoring pairs analysis, classification of such
      progressors was observed with a high success rate. Overall, the data provide a
      reference of temporal changes in the serum proteome in healthy children and
      children progressing to type 1 diabetes, including new protein candidates, the
      levels of which change before clinical diagnosis. 

PMID- 25616279
TI  - Demystifying theory and its use in improvement.
AB  - The role and value of theory in improvement work in healthcare has been seriously
      underrecognised. We join others in proposing that more informed use of theory can
      strengthen improvement programmes and facilitate the evaluation of their
      effectiveness. Many professionals, including improvement practitioners, are
      unfortunately mystified-and alienated-by theory, which discourages them from
      using it in their work. In an effort to demystify theory we make the point in
      this paper that, far from being discretionary or superfluous, theory ('reason
      giving'), both informal and formal, is intimately woven into virtually all human
      endeavour. We explore the special characteristics of grand, mid-range and
      programme theory; consider the consequences of misusing theory or failing to use
      it; review the process of developing and applying programme theory; examine some
      emerging criteria of 'good' theory; and emphasise the value, as well as the
      challenge, of combining informal experience-based theory with formal, publicly
      developed theory. We conclude that although informal theory is always at work in
      improvement, practitioners are often not aware of it or do not make it explicit.
      The germane issue for improvement practitioners, therefore, is not whether they
      use theory but whether they make explicit the particular theory or theories,
      informal and formal, they actually use. 

PMID- 25616280
TI  - End of life care services are in limbo after phasing out of Liverpool Care
      Pathway, MPs hear.

PMID- 25616282
TI  - Stability of transgene expression in reduced allergen peanut (Arachis hypogaea
      L.) across multiple generations and at different soil sulfur levels.
AB  - Transgenic peanut (Arachis hypogaea L.) containing a gene designed for RNA
      interference (RNAi) showed stable complete silencing of Ara h 2 and partial
      silencing of Ara h 6, two potent peanut allergens/proteins, along with minimal
      collateral changes to other allergens, Ara h 1 and Ara h 3, across three
      generations (T3, T4, and T5) under field conditions. Different soil sulfur levels
      (0.012, 0.3, and 3.0 mM) differentially impacted sulfur-rich (Ara h 2, Ara h 3,
      and Ara h 6) versus sulfur-poor (Ara h 1) proteins in non-transgenic versus
      transgenic peanut. The sulfur level had no effect on Ara h 1, whereas low sulfur
      led to a significant reduction of Ara h 3 in transgenic and non-transgenic seeds
      and Ara h 2 and Ara h 6 in non-transgenic but not in transgenic peanuts because
      these proteins already were reduced by gene silencing. These results demonstrate
      stability of transgene expression and the potential utility of RNAi in allergen
      manipulation. 

PMID- 25616281
TI  - The ADP/ATP carrier and its relationship to oxidative phosphorylation in
      ancestral protist trypanosoma brucei.
AB  - The highly conserved ADP/ATP carrier (AAC) is a key energetic link between the
      mitochondrial (mt) and cytosolic compartments of all aerobic eukaryotic cells, as
      it exchanges the ATP generated inside the organelle for the cytosolic ADP.
      Trypanosoma brucei, a parasitic protist of medical and veterinary importance,
      possesses a single functional AAC protein (TbAAC) that is related to the human
      and yeast ADP/ATP carriers. However, unlike previous studies performed with these
      model organisms, this study showed that TbAAC is most likely not a stable
      component of either the respiratory supercomplex III+IV or the ATP synthasome but
      rather functions as a physically separate entity in this highly diverged
      eukaryote. Therefore, TbAAC RNA interference (RNAi) ablation in the insect stage
      of T. brucei does not impair the activity or arrangement of the respiratory chain
      complexes. Nevertheless, RNAi silencing of TbAAC caused a severe growth defect
      that coincides with a significant reduction of mt ATP synthesis by both substrate
      and oxidative phosphorylation. Furthermore, TbAAC downregulation resulted in a
      decreased level of cytosolic ATP, a higher mt membrane potential, an elevated
      amount of reactive oxygen species, and a reduced consumption of oxygen in the
      mitochondria. Interestingly, while TbAAC has previously been demonstrated to
      serve as the sole ADP/ATP carrier for ADP influx into the mitochondria, our data
      suggest that a second carrier for ATP influx may be present and active in the T.
      brucei mitochondrion. Overall, this study provides more insight into the delicate
      balance of the functional relationship between TbAAC and the oxidative
      phosphorylation (OXPHOS) pathway in an early diverged eukaryote. 

PMID- 25616283
TI  - [Gene mutations and clinical characteristics in children with juvenile
      myelomonocytic leukemia].
AB  - OBJECTIVE: To study gene mutations and clinical features in children with
      juvenile myelomonocytic leukemia (JMML). METHODS: The clinical data of 14
      children who were diagnosed with JMML and were examined for the detection of
      common gene mutations were retrospectively analyzed. RESULTS: Eleven (79%) out of
      14 cases were male, and 3 (21%) were female. The median age at diagnosis was 2.0
      years (age range: 0.6-6.0 years). Among 14 cases, there were 4 cases (29%) with
      PTPN11 mutation, 3 cases (21%) with N-RAS mutation, 1 case (7%) with PTPN11
      mutation and K-RAS mutation, and 6 cases (43%) without any mutation. All four
      cases in the PTPN11 mutation group were male, and their median age was 2.5 years;
      interval from onset to diagnosis was 1.0 month; the white blood cell (WBC) count
      and absolute monocytes in peripheral blood were significantly higher, while the
      platelet (PLT) count was lower, as compared with the other three groups; they
      were followed up, and 3 cases died and 1 case had a progressive disease. In the N
      RAS mutation group, there were two male cases and one female case, and their
      median age was 2.0 years; interval from onset to diagnosis was 13.7 months; after
      follow-up, 2 cases died and 1 case did not have an obviously progressive disease.
      CONCLUSIONS: PTPN11 mutation is the most common mutation in JMML. The cases with
      PTPN11 mutation often have higher WBC count and absolute monocytes in peripheral
      blood, a lower PLT count, and a rapid disease progression, and their clinical
      outcomes are poor. The cases with N-RAS mutation have a slow disease progression.
      The clinical characteristics of the patients with compound mutations are not sure
      because of the small number of cases, and further clinical observation is
      indispensable.

PMID- 25616284
TI  - [Methylation of the genes in the 9P21 region in children with acute myeloid
      leukemia].
AB  - OBJECTIVE: To investigate the methylation rate of cyclin-dependent kinase
      inhibitor 2A (CDKN2A) and cyclin-dependent kinase inhibitor 2B (CDKN2B) in the
      9P21 region in children with acute myeloid leukemia (AML) and the association of
      gene methylation with clinical features and outcomes. METHODS: The clinical data
      of 58 children who were newly diagnosed with AML between January 2010 and
      December 2012 were retrospectively analyzed. Thirty-eight healthy children were
      recruited as the control group. Genomic DNA was extracted from bone marrow or
      peripheral blood of the 58 patients and 38 healthy children. The methylation
      status of CDKN2A and CDKN2B was analyzed by methylation-specific multiplex
      ligation-dependent probe amplification. RESULTS: Gene methylation was not found
      in healthy children. Methylation probes of 44 patients were detected in 58
      patients. The methylation of CDKN2A was detected with 136 bp and 237 bp
      methylation probes. The methylation of CDKN2B was detected with 130 bp, 210 bp,
      220 bp, and 417 bp methylation probes. The methylation rate of CDKN2A was 5%,
      while the methylation rate of CDKN2B was 76%. The methylation detected by some
      probes was associated with sex, hemoglobin, and platelet count at the first
      visit. CONCLUSIONS: The methylation of CDKN2B is a common event in children with
      AML, while the methylation of CDKN2A is relatively rare.

PMID- 25616285
TI  - [Influence of thymidylate synthase gene polymorphisms on high-dose methotrexate
      related toxicities in childhood acute lymphoblastic leukemia].
AB  - OBJECTIVE: To investigate the influence of thymidylate synthase (TS) gene
      polymorphisms on high-dose methotrexate (HD-MTX)-related toxicities in childhood
      acute lymphoblastic leukemia (ALL). METHODS: A total of 73 children who were
      diagnosed with ALL between March 2011 and March 2013 were included into this
      study. Genomic DNAs were extracted from their peripheral blood. And then the
      genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The
      toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and
      recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were
      measured. RESULTS: The main HD-MTX-related toxicities of 73 patients receiving HD
      MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia,
      liver toxicity, mucosal damage, and gastrointestinal reactions. There were no
      significant differences in the incidence rate of HD-MTX-related toxicities
      between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05).
      TS 5'-UTR genotype was not significantly correlated with plasma MTX
      concentrations at 42-48 hours after chemotherapy (P>0.05). CONCLUSIONS: TS gene
      polymorphisms have no influence on the incidence of HD-MTX-related toxicities in
      childhood ALL.

PMID- 25616286
TI  - [Clinical features of childhood refractory cytopenia].
AB  - OBJECTIVE: To study the clinical features of patients with refractory cytopenia
      of childhood (RCC). METHODS: The clinical data of 1 420 children (0-14 years old)
      with an initial diagnosis of non-severe aplastic anemia between January 1990 and
      June 2013 were retrospectively analyzed. Bone marrow cell morphology and
      histopathology were re-evaluated, and the patients were re-classified using the
      criteria proposed in the 2008 edition of the World Health Organization
      classification of RCC in hematopoietic and lymphoid tumor tissues. The clinical
      outcomes were followed up every 3-6 months. RESULTS: Among all the 1 420 cases,
      152 (10.7%) were reassessed as RCC. Patients with RCC had a lower level of
      hemoglobin and a higher percentage of fetal hemoglobin than those with non-severe
      aplastic anemia. Of the patients with RCC, 21.5% showed abnormal karyotypes at
      diagnosis. The median follow-up period for all patients was 36 months (ranging
      from 1 to 283 months). The rates of complete response, partial response, and no
      response to cyclosporine and androgen treatment in RCC patients were 19.0%,
      26.7%, and 54.3%, respectively. The 5- and 10-year prospective overall survival
      rates of RCC patients were 87.9% and 72.4%, respectively. The 5- and 10-year
      prospective clonal evolution rates were 15.3% and 20.0%, respectively. The 2-year
      prospective incidence of newly diagnosed karyotype abnormality after the initial
      diagnosis was 3.6%. The 5- and 10-year prospective leukemia transformation rates
      were 10.0% and 20.0%, respectively. CONCLUSIONS: RCC shows clinical features
      similar to adult myelodysplastic syndrome. Children with RCC have a poor
      prognosis, an increased risk of transformation to leukemia, and a low response
      rate to cyclosporine treatment.

PMID- 25616287
TI  - [Association between Helicobacter pylori infection and newly diagnosed childhood
      immune thrombocytopenia].
AB  - OBJECTIVE: To study the role of Helicobacter pylori (H. pylori) infection in
      newly diagnosed childhood immune thrombocytopenia (ITP). METHODS: A total of 495
      children with newly diagnosed ITP who were hospitalized for the first time
      between January 2011 and December 2013 were included as the case group. A total
      of 123 children with common respiratory tract infection (not ITP or other
      diseases of blood system) were randomly selected as the control group. All
      patients were divided into four groups by age: <1 year group, 1-3 years group, 3
      7 years group, and 7-14 years group. The incidence of H. pylori infection in all
      age groups and the clinical outcomes of ITP children with or without H. pylori
      infection were retrospectively analyzed. RESULTS: The incidence rate of H. pylori
      infection in the case group increased with increasing age. There was no
      significant difference in the incidence rate of H. pylori infection between the
      case and the control groups among subjects of the same age (P>0.05). All the ITP
      patients were not given anti-H. pylori treatment and only received the treatment
      (glucocorticoid and/or immunoglobulin) for ITP, and their remission rate declined
      with increasing age. There was no significant difference in the remission rate
      between the ITP children with H. pylori infection and those without H. pylori
      infection in the same age group (P>0.05). CONCLUSIONS: H. pylori infection may
      not be a major cause of ITP in children, and the clinical outcomes of children
      with acute ITP are not affected by receiving anti-H. pylori treatment or not.

PMID- 25616288
TI  - [Clinical features of childhood hemophagocytic syndrome and its association with
      human parvovirus B19 infection].
AB  - OBJECTIVE: To investigate the association of childhood hemophagocytic syndrome
      (HPS) with human parvovirus B19 (HPVB19) infection, and to analyze the clinical
      features of this disease. METHODS: ELISA and quantitative real-time PCR were used
      to detect HPVB19-IgM, HPVB19-IgG and HPVB19-DNA in 65 children with HPS (HPS
      group) and 65 healthy children (control group). The HPS group was divided into
      HPVB19-infected (n=14) and non-infected (n=51) groups according to the detection
      results of HPVB19-DNA. The clinical data of two groups were compared. RESULTS:
      The positive rate of HPVB19-IgM in the HPS group (26%, 17/65) was significantly
      higher than that in the control group (9%, 6/65) (P=0.011), and there was no
      significant difference in the positive rate of HPVB19-IgG between the HPS (38%,
      25/65) and control groups (29%, 19/65) (P=0.266). The infection rate of HPVB19 in
      the HPS group (22%, 14/65) was significantly higher than that in the control
      group (3%, 2/65) (P=0.001). Compared with the non-infected group, the HPVB19
      infected group had significantly lower platelet count and hemoglobin level on
      admission, significantly more severe liver function damage, a significantly
      earlier onset time, and a significantly longer course of disease (P<0.05).
      CONCLUSIONS: The pathogenesis of HPS may be associated with HPVBl9 infection.
      HPVBl9-infected children with HPS have more acute onset, more severe clinical
      manifestations, and a longer disease duration.

PMID- 25616289
TI  - [A prospective, randomized, controlled clinical study of Huai Qi Huang granules
      in treatment of childhood primary nephrotic syndrome].
AB  - OBJECTIVE: To study the efficacy of Huai Qi Huang granules in the treatment of
      childhood primary nephrotic syndrome. METHODS: Between July 2009 and December
      2011, patients who were admitted and diagnosed for the first time as childhood
      primary nephrotic syndrome were randomized into a treatment group (Huai Qi Huang
      granules plus glucocorticoid; n=23) and a control group (glucocorticoid alone;
      n=19) for a prospective study. The two groups were compared for regression time
      of edema, time to urinary protein clearance, relapse rate, incidence of
      infection, dosage of glucocorticoid, and humoral and cellular immunological
      indicators. RESULTS: There were no significant differences in regression time of
      edema, time to urinary protein clearance, and relapse rate between the treatment
      and control groups (P>0.05). The treatment group had significantly lower
      incidence of infection and daily dose of glucocorticoid (at month 6) than the
      control group (P<0.05). Humoral and cellular immunological indicators showed no
      significant differences between the two groups (P>0.05). No Huai Qi Huang-related
      adverse events were observed in this study. CONCLUSIONS: Huai Qi Huang granules
      treatment can reduce the dose of glucocorticoid and the incidence of infection in
      children with primary nephrotic syndrome and has a favourable safety.

PMID- 25616290
TI  - [Serum adiponectin levels in children with Kawasaki disease].
AB  - OBJECTIVE: To explore the change in serum adiponectin levels and its significance
      in children with Kawasaki disease (KD). METHODS: Forty-five KD patients were
      enrolled in this study, including 18 with coronary artery lesions (CAL group) and
      27 without coronary artery lesions (NCAL group). Twenty healthy children were
      recruited to the control group. Enzyme-linked immunosorbent assay was used to
      measure serum adiponectin levels, and an automatic biochemical analyzer was used
      to measure the levels of triglyceride (TG), total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL
      C). RESULTS: The serum adiponectin levels in the CAL and NCAL groups were
      significantly lower than in the control group during the acute phase, subacute
      phase, and recovery phase (P<0.01), with lower levels observed during the acute
      phase and subacute phase (P<0.01). Compared with the NCAL group, the CAL group
      had significantly higher serum levels of adiponectin during the acute phase and
      recovery phase (P<0.05). The levels of TC, HDL, and LDL in the NCAL and CAL
      groups were significantly lower than in the control group (P<0.05). The levels of
      serum adiponectin in KD patients were positively correlated with the levels of
      TC, TG, and C-reactive protein and the occurrence of CAL (r=0.31, 0.30, 0.34, and
      0.35, respectively; P<0.05). CONCLUSIONS: Children with KD have metabolic
      disorders of blood lipids and reduced serum adiponectin levels. Reduced serum
      adiponectin levels may be the result of systemic inflammation, while increased
      adiponectin levels may be closely associated with the occurrence of CAL.

PMID- 25616291
TI  - [DUOX2 mutations in children with congenital hypothyroidism].
AB  - OBJECTIVE: To study the features of DUOX2 mutations and genotype-phenotype
      relationship in children with congenital hypothyroidism (CH), in order to provide
      evidence for gene diagnosis and gene treatment of CH. METHODS: Blood samples were
      collected from 10 CH children with thyromegaly. Genomic DNA was extracted from
      peripheral blood leukocytes. All exons of DUOX2 gene were analyzed using PCR and
      direct sequencing. RESULTS: G3632A mutation in the exon 28 of DUOX2 that may
      result in arginine to histidine substitution at codon 1211 was found in one
      patient. T2033C mutation in the exon 17 of DUOX2 that may result in histidine to
      arginine substitution at codon 678 was found in three patients. They were all
      heterozygous mutations. CONCLUSIONS: Heterozygous mutations in DUOX2 may affect
      protein function and cause CH. The relationship between DUOX2 genotypes and
      clinical phenotypes is unclear and needs further studies.

PMID- 25616292
TI  - [Analysis of neonatal screening results for congenital hypothyroidism in parts of
      Yunnan Province, China].
AB  - OBJECTIVE: To summarize and analyze neonatal screening results for congenital
      hypothyroidism (CH) in parts of Yunnan Province, China. METHODS: A total of 236
      218 newborns (121 463 males and 114 755 females) who were born in Zhaotong City,
      Qujing City, Lijiang City, and Diqing Tibetan Autonomous Prefecture of Yunnan
      Province, China, between July 2012 and April 2014 were screened for CH. The
      original blood smear was re-tested if the thyroid stimulating hormone (TSH) level
      in heel blood was >=8 MUIU/L in the initial screening. The newborns with positive
      TSH results were called back for further diagnosis by measuring blood TSH and
      free thyroxine (FT4) levels. RESULTS: Among 236 218 newborns, the pass rate of
      blood smears, re-acquisition rate of unqualified blood smears, and recall rate of
      suspected cases were 96.67%, 81.75%, and 73.02%, respectively. Sixty-six cases of
      CH were confirmed, among which 36 were male infants and 30 were female infants
      (P>0.05). The incidence rate of CH was 1/3 579, which was significantly lower
      than the national average rate (1/2 034; P<0.01). The gestational age of CH
      newborns was mostly between 37 to 42 weeks, and only 3% were born at a
      gestational age of >42 weeks. Most of the CH newborns had normal birth weight.
      The CH newborns with a body length of <50 cm accounted for 32%. CONCLUSIONS: The
      incidence of CH in Yunnan Province is lower than the national average. There are
      no specific clinical features in CH newborns. The neonatal screening in Yunnan
      Province needs further improvement.

PMID- 25616293
TI  - [Comparisons of risk factors for low birth weight between Han and Uygur full-term
      infants].
AB  - OBJECTRIVE: To compare the differences in risk factors for low birth weight (LBW)
      between Han and Uygur full-term infants and to provide a basis for the prevention
      of LBW in newborn infants. METHODS: Eighty-seven full-term LBW infants (38 Hans
      and 49 Uygurs) between March 2013 and June 2014 were selected as the case group,
      and 186 full-term normal birth weight infants (92 Hans and 94 Uygurs) were
      selected as the control group. A questionnaire survey was performed to
      investigate the related factors for LBW. Multivariate logistic regression
      analysis was carried out to determine the risk factors for LBW. RESULTS: The
      birth weights in Uyghur LBW infants were lower than in Han ones (P<0.05).
      Multivariate logistic regression analysis showed that drinking (OR=2.472,
      P=0.015) and smoking (OR=2.323, P=0.007) by the father, pregnancy complications
      (OR=14.377, P<0.001), and times of pregnancy (OR=2.995, P=0.001) were the risk
      factors for LBW in Han infants, while drinking by the father (OR=1.968, P=0.007),
      times of pregnancy (OR=1.953, P=0.005), pregnancy complications (OR=10.283,
      P=0.002), and poor indoor environment (OR=1.367, P=0.027) were the risk factors
      for LBW in Uyghur infants. CONCLUSIONS: There are differences in physical growth
      between Han and Uygur LBW infants. Han and Uygur infants share the same
      traditional risk factors for LBW, such as father's harmful behaviors like
      drinking, times of pregnancy, and pregnancy complications, however, the indoor
      environment also plays a role in the occurrence of LBW in Uygur infants.

PMID- 25616294
TI  - [Value of early application of different doses of amino acids in parenteral
      nutrition among preterm infants].
AB  - OBJECTIVE: To study the short-term response and tolerance of different doses of
      amino acids in parenteral nutrition among preterm infants. METHODS: This study
      included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and
      were admitted to the hospital within 24 hours of birth between March 2013 and
      June 2014. According to the early application of different doses of amino acids,
      they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase
      of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28,
      2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per
      day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0
      g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition
      and enteral nutrition support were also applied. RESULTS: The maximum weight loss
      was lower and the growth rate of head circumference was greater in the high-dose
      group than in the low-dose group (P<0.05). The infants in the medium- and high
      dose groups had faster recovery of birth weight, earlier attainment of 100
      kcal/(kg.d) of enteral nutrition, shorter duration of hospital stay, and less
      hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen
      (BUN) levels in the high-dose group increased compared with the other two groups
      7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate,
      bilirubin, and transaminase and the incidence of complications showed no
      significant differences between groups (P>0.05). CONCLUSIONS: Parenteral
      administration of high-dose amino acids in preterm infants within 24 hours after
      birth can improve the short-term nutritional status of preterm infants, but there
      is a transient increase in BUN level.

PMID- 25616295
TI  - [Relationship between serum adiponectin and bone mineral density in preterm
      infants].
AB  - OBJECTIVE: To examine serum adiponectin level in preterm infants and to evaluate
      the relationship between serum adiponectin and bone mineral density in preterm
      infants. METHODS: Seventy-two appropriate-for-gestational-age neonates were
      classified into three groups according to their gestational ages: early preterm
      (31-33(+6) weeks, 13 cases), late preterm (34-36(+6) weeks, 16 cases), and full
      term (37-42 weeks, 43 cases). Venous blood was collected at one week of their
      life to measure serum adiponectin concentration. During the period, omnisense
      ultrasound bone sonometer was applied to measure speed of sound (SOS) of the left
      tibia. RESULTS: The median of tibia SOS in the early preterm group was
      significantly lower than in the late preterm and full term groups (P<0.05), and
      the median of tibia SOS in the late preterm group was lower than in the full-term
      group (P<0.05). Serum adiponectin level was lowest in the early preterm group,
      and the full-term group had the highest serum adiponectin level. Serum
      adiponectin level was positively correlated with tibia SOS in preterm infants
      (r=0.664, P<0.05). According to the result of multivariate linear stepwise
      regression analysis, serum adiponectin and birth weight were independent
      predictor of tibia SOS in preterm infants. CONCLUSIONS: Serum adiponectin level
      is lower in preterm infants than that in full-term infants. There is a positive
      correlation between serum adiponectin and bone mineral density in preterm
      infants.

PMID- 25616296
TI  - [Clinical outcomes of twin pregnancies conceived by in vitro fertilization
      compared with spontaneous twin pregnancies].
AB  - OBJECTIVE: To compare the maternal and perinatal outcomes of twin pregnancies
      conceived by in vitro fertilization (IVF) with outcomes of spontaneous twin
      pregnancies. METHODS: A retrospective analysis was conducted between January 2010
      and April 2014 to investigate the maternal age, gestation length, modes of
      delivery, pregnancy complications and neonatal physical development, birth
      defects and perinatal diseases in 106 IVF-assisted twin pregnancies (IVF group)
      and 256 spontaneous twin pregnancies (control group). RESULTS: The mothers in the
      IVF group were significantly older than those in the control group (32+/-4 years
      vs 28+/-4 years, P<0.05). The incidence rates of gestational hypertension and
      gestational diabetes in the IVF group were significantly higher than in the
      control group (P<0.05). No significant differences were observed for neonatal
      physical development, the incidence of birth defects, and the incidence and
      mortality of perinatal diseases (P>0.05). CONCLUSIONS: Twins conceived by IVF
      have similar outcomes as spontaneously conceived twins in the perinatal period.
      However, special attention is needed to monitor the levels of blood pressure and
      blood glucose for pregnant women with twins conceived by IVF during prenatal
      checkups.

PMID- 25616297
TI  - [Serum levels of 25-hydroxyvitamin D in children with autism spectrum disorders].
AB  - OBJECTIVE: To examine serum 25-hydroxyvitamin D levels in children with autism
      spectrum disorders (ASD) and to explore the relationship between vitamin D level
      and ASD. METHODS: Serum levels of 25-hydroxyvitamin D levels were determined by
      the HPLC-MS/MS method in 117 children with newly diagnosed ASD and 109 healthy
      controls. Vitamin D status were classified into normal (>30 ng/mL), insufficiency
      (10-30ng/mL) and deficiency (<10 ng/mL) according to 25-hydroxyvitamin D levels.
      RESULTS: Serum level of 25-hydroxyvitamin D (19+/-9 ng/mL)in children with ASD
      was significantly lower than that in healthy controls (36+/-13 ng/mL; P<0.01).
      The rate of vitamin D insufficiency plus deficiency in the ASD group was
      significantly higher than in the control group (89.7% vs 52.3%; P<0.01).
      CONCLUSIONS: Vitamin D insufficiency or deficiency is common in children with ASD
      and might be as one of the environmental or genetic factors for ASD.

PMID- 25616298
TI  - [Status of penis and testicular development and effects of overweight/obesity on
      them in boys in the Zhengzhou area].
AB  - OBJECTIVE: To evaluate the current status of penis and testicular development in
      boys and the effects of overweight/obesity on their development in the Zhengzhou
      area of Henan Province. METHODS: Height, weight, waist circumference, hip
      circumference, penis length and testicular volume were measured in 3 546 4 to 12
      year-old boys. The penis length and testicular volume were compared between the
      overweight/obesity and normal weight groups. RESULTS: Before 9 years of age, the
      testicular volume was progressively smaller, and after 9 years old, it gradually
      increased. By the age of 11, it increased rapidly. The penis length increased
      gradually between 4 and 11 years of age, and after the age of 11 it increased
      rapidly. Phimosis was found in 144 cases (4.01%) and cryptorchidism was found in
      18 cases (0.51%). A total of 639 (18.02%) boys were overweight or obese among 3
      546 boys. At the ages of 6 and 7 years, the testicular volume in the
      overweight/obesity group was greater than in the normal control group (P<0.05).
      The penis length in the overweight/obesity group was significantly shorter than
      in the normal control group (P<0.05) by the age of 11 years. The correlation
      analysis showed that the testicular volume at the ages of 4 and 5 years was
      positively correlated with height, weight, BMI, waist circumference and hip
      circumference in overweight/obese boys. The penis length at the ages of 7 and 8
      years was negatively correlated with weight, waist circumference and hip
      circumference. By the age of 12 years, the penis length was positively correlated
      with the height. CONCLUSIONS: The development of penis and testicles in boys in
      the Zhengzhou area is in line with the level of sex development of Chinese boys.
      Overweight/obesity adversely affects the development of penis and testicles.

PMID- 25616299
TI  - [A complicated case study: Hennekam syndrome].
AB  - Hennekam syndrome (HS) is a rare autosomal recessive syndrome characterized by
      defective lymphatic development. A 34-month-old boy with HS and who had
      unexplained developmental retardation and hypoalbuminemia as main clinical
      manifestations is reported here. He had a history of generalized edema and poor
      feeding. He was not thriving well. He manifested as facial anomalies
      (hypertelorism, flat nasal bridge and flat face), fracture of teeth, and
      superficial lymph nodes enlargement. He had low serum total protein, low serum
      albumin, and low serum immunoglobulin levels. Duodenal bulb biopsy revealed
      lymphangiectasia. Color Doppler ultrasound, magnetic resonance imaging and CT
      scan showed multi-site lymphangioma, and HS was thus confirmed. Mutations in
      CCBE1 and FAT4 have been found responsible for the syndrome in a part of
      patients. Diagnosis of the disease depends on the familial history, clinical
      signs, pathological findings and genetic tests. 

PMID- 25616300
TI  - [Effects of glucocorticoid on RAGE-NF-kappaB pathway in hyperoxia-induced lung
      tissues of neonatal rats].
AB  - OBJECTIVE: To explore the change of RAGE-NF-kappaB signaling pathway during the
      course of hyperoxia-induced lung injury in newborn rats, and the effect of
      glucocorticoid on this pathway. METHODS: Twenty-four Sprague-Dawley neonatal rats
      were randomly divided into three groups (n=8 each) : sham control (control
      group), hyperoxia-induced acute lung injury (model group) and glucocorticoid
      treated acute lung injury (glucocorticoid group). Rats were sacrificed at 13 days
      after birth. RAGE and NF-kappaB expression levels in lung tissues were detected
      by reverse transcription polymerase chain reaction, Western blot and
      immunohistochemistry analysis. The levels of tumor necrosis factor alpha (TNF
      alpha) and sRAGE in bronchoalveolar lavage fluid (BALF) and serum were measured
      using ELISA. Lung damage was evaluated by histological examinations. RESULTS:
      RAGE and NF-kappaB mRNA and protein expression levels in lung tissues were
      significantly increased in the model and glucocorticoid groups compared with the
      control group (P<0.05). Serum RAGE concentrations were significantly increased
      but RAGE concentrations in BALF were significantly reduced in the model and
      glucocorticoid groups compared with the control group (P<0.05). RAGE and NF
      kappaB expression at both mRNA and protein levels in lung tissues was
      significantly lower in the glucocorticoid group than in the model group (P<0.05).
      RAGE concentrations were significantly lower in serum (P<0.05), but were higher
      in BALF (P<0.05) in the glucocorticoid group than in the model group.
      CONCLUSIONS: RAGE-NF-kappaB pathway plays an important role in hyperoxia-induced
      lung injury in neonatal rats, and glucocorticoid administration may play a
      protective role against the lung injury by down-regulating RAGE-NF-kappaB
      signaling pathway.

PMID- 25616301
TI  - [Effect of budesonide aerosol treatment on expression of glucocorticoid receptor
      and nuclear factor-kappaB in asthmatic mice].
AB  - OBJECTIVE: To study the effect of budesonide aerosol inhalation on the expression
      of glucocorticoid receptor (GR) and nuclear factor (NF)-kappaB in asthmatic mice.
      METHODS: Twenty-four healthy male BALB/c mice aged 6 to 8 weeks were randomly
      divided into three groups (n=8 each): normal saline (control group), asthma model
      (asthma group) and budesonide-treated asthma (BUD group). Asthma was induced by
      intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide suspension
      and aerosol inhalation of OVA solution. Mice were sacrificed 24 hours after the
      last challenge. Eosinophil count in the bronchoalveolar lavage fluid (BALF) was
      determined. Pathological examination of the lung tissues was performed and the
      expression levels of GR and NF-kappaB were measured by immunohistochemical
      analysis. RESULTS: Eosinophil count in the BALF was significantly higher in the
      asthma and BUD groups than in the control group (P<0.05). BUD treatment decreased
      eosinophil count in the BALF compared with the asthma group (P<0.05). The lung
      tissues in the BUD group showed a less severe infiltration of eosinophils and
      lymphocytes compared with the asthma group. The percentage of GR-positive cells
      in the asthma group decreased significantly compared with the control group
      (P<0.05), and the percentage of GR-positive cells in the BUD group increased
      significantly compared with the asthma group (P<0.05). Compared with the control
      group, the percentage of NF-kappaB-positive cells increased significantly in the
      asthma group (P<0.05), and the percentage of NF-kappaB positive cells in the BUD
      group was significantly reduced compared with the asthma group (P<0.05).
      CONCLUSIONS: The action mechanism of budesonide in treating asthmatic mice may be
      related to the upregulation of GR expression and the inhibition of NF-kappaB
      activity.

PMID- 25616302
TI  - [Clinical analysis of childhood pseudomembranous colitis].

PMID- 25616303
TI  - [Misdiagnosis of aneurysm of thoracic aorta in 6 children].

PMID- 25616304
TI  - [Cerebral venous sinus thrombosis and pulmanary embolism in a child].

PMID- 25616305
TI  - [A case report of sigmoid sinus thrombosis following mastoiditis].

PMID- 25616306
TI  - [Defectiveness of bone marrow mesenchymal stem cells in acquired aplastic
      anemia].
AB  - The defectiveness of bone marrow mesenchymal stem cells (BM-MSCs) in acquired
      aplastic anemia (AA) has been a frequent research topic in recent years. This
      review summarizes the defectiveness of BM-MSCs which is responsible for the
      mechanism of acquired AA and the prospective application of BM-MSCs in the
      treatment of acquired AA. An increasingly number of laboratory statistics has
      demonstrated that the defectiveness of BM-MSCs is more likely to play an
      important role in the pathogenesis of AA, namely, the apparently different
      biological characteristics and gene expression profiles, the decreased ability of
      supporting hematopoiesis as well as self-renewal and differentiation, and the
      exhaustion of regulating immune response of hematopoietic environment. Those
      abnormalities continuously prompt AA to become irreversible bone marrow failure
      along with the imbalanced immunity. With deepening research on MSCs, infusion of
      MSCs for the primary purpose of recovering hematopoietic microenvironment may
      become a new approach for the treatment of AA. 

PMID- 25616307
TI  - [Research advances in pediatric nonalcoholic fatty liver disease].
AB  - In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because
      of the growing prevalence of obesity and overweight in the pediatric population.
      It has become the most common form of chronic liver diseases in children and the
      related research on NAFLD is expanded. The "two-hit" and "multiple hit"
      hypothesis have been widely accepted, and some research has shown that genetic,
      diet structure and environmental factors appear to play a crucial role in the
      development of pediatric NAFLD. Though it is expected by researchers, there is
      not an available satisfactory noninvasive marker for the diagnosis of this
      disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD
      have been developed. There is currently no established special therapy, and
      lifestyle intervention should be adequate for most cases of NAFLD in children.
      This article reviews the advances in the current knowledge and ideas concerning
      pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring
      methods for this disease. 

PMID- 25616308
TI  - Vanishing Weakness and Persistent Cardiac Dysrhythmia: Are We Dealing with
      Andersen Tawil Syndrome?
AB  - Andersen Tawil Syndrome (ATS) is a very rare type of periodic paralysis; the
      authors present a case report from South India with features that have not been
      reported earlier. This case suggests many unexplored hypotheses for the disease
      and argues the need for physician sensitization of this entity. 

PMID- 25616309
TI  - Effect of vitamin D supplementation on moderate to severe bronchial asthma:
      correspondence 2.

PMID- 25616310
TI  - Editorial: advances in neurology.

PMID- 25616311
TI  - Political factors behind US global AIDS programmes slow-down.

PMID- 25616312
TI  - Acute pancreatitis.
AB  - Acute pancreatitis, an inflammatory disorder of the pancreas, is the leading
      cause of admission to hospital for gastrointestinal disorders in the USA and many
      other countries. Gallstones and alcohol misuse are long-established risk factors,
      but several new causes have emerged that, together with new aspects of
      pathophysiology, improve understanding of the disorder. As incidence (and
      admission rates) of acute pancreatitis increase, so does the demand for effective
      management. We review how to manage patients with acute pancreatitis, paying
      attention to diagnosis, differential diagnosis, complications, prognostic
      factors, treatment, and prevention of second attacks, and the possible transition
      from acute to chronic pancreatitis. 

PMID- 25616313
TI  - Mentalization-based therapy (MBT): an overview.
AB  - OBJECTIVE: This paper provides an overview of mentalization-based therapy (MBT).
      Multiple strands of research evidence converge to suggest that affect
      dysregulation, impulsivity and unstable interpersonal relationships are core
      features of borderline personality disorder (BPD). The MBT approach to BPD
      attempts to provide a theoretically consistent way of conceptualising the inter
      relationship of these features. METHODS: MBT makes mentalizing a core focus of
      therapy and was initially developed for the treatment of BPD in routine clinical
      services, delivered in group and individual modalities. This article provides a
      brief overview of mentalizing and its relevance to BPD, provides an overview of
      MBT and notes a number of current trends in MBT. RESULTS: MBT provides clinicians
      with an empirically supported approach to BPD and its treatment. CONCLUSIONS:
      Whilst mentalizing is viewed as an integrative framework for therapy, more
      knowledge is needed as to which of the therapies are of most benefit for
      individual patients.

PMID- 25616314
TI  - Assessing patient satisfaction with a multidisciplinary gender dysphoria clinic
      in Melbourne.
AB  - OBJECTIVES: The Gender Dysphoria Clinic in Melbourne, Australia, assessed patient
      outcome by focusing on patients' subjective evaluation of the healthcare services
      they received through the clinic. METHODS: A satisfaction survey, which was
      previously used in two established gender clinics in the US and UK, was adapted
      and then administered to consecutive patients who attended the Gender Dysphoria
      Clinic during a 1-month period. RESULTS: A total of 127 surveys were available
      for analysis: 88% of patients reported being satisfied with the services they
      received. Patients' perceived level of distress reduced significantly, following
      their involvement with the Gender Dysphoria Clinic. Feeling understood and heard
      in a non-judgmental manner by a specialist in the field of gender dysphoria was
      the most positive aspect of service provision. The most negative aspect of the
      clinic was a lengthy waiting list. CONCLUSIONS: Although the majority of trans
      and-gender-diverse patients attending the Gender Dysphoria Clinic were satisfied
      with the service they received, there is a need to identify strategies to
      facilitate timely access to the clinic.

PMID- 25616315
TI  - [Burnout syndrome among physicians].

PMID- 25616316
TI  - Comparison of species identification of endocarditis associated viridans
      streptococci using rnpB genotyping and 2 MALDI-TOF systems.
AB  - Streptococcus spp. are important causes of infective endocarditis but challenging
      in species identification. This study compared identification based on sequence
      determination of the rnpB gene with 2 systems of matrix-assisted laser desorption
      ionization-time of flight mass spectrometry, MALDI Biotyper (Bruker) and VITEK MS
      IVD (bioMerieux). Blood culture isolates of viridans streptococci from 63
      patients with infective endocarditis were tested. The 3 methods showed full
      agreement for all 36 isolates identified in the Anginosus, Bovis, and Mutans
      groups or identified as Streptococcus cristatus, Streptococcus gordonii, or
      Streptococcus sanguinis. None of the methods could reliably identify the 23
      isolates to the species level when designated as Streptococcus mitis,
      Streptococcus oralis, or Streptococcus tigurinus. In 7 isolates classified to the
      Mitis group, the rnpB sequences deviated strikingly from all reference sequences,
      and additional analysis of sodA and groEL genes indicated the occurrence of yet
      unidentified Streptococcus spp.

PMID- 25616317
TI  - Self-care Barriers Reported by Emergency Department Patients With Acute Heart
      Failure: A Sociotechnical Systems-Based Approach.
AB  - STUDY OBJECTIVE: We pilot tested a sociotechnical systems-based instrument that
      assesses the prevalence and nature of self-care barriers among patients
      presenting to the emergency department (ED) with acute heart failure. METHODS: A
      semistructured instrument for measuring self-reported self-care barriers was
      developed and administered by ED clinicians and nonclinician researchers to 31 ED
      patients receiving a diagnosis of acute heart failure. Responses were analyzed
      with descriptive statistics and qualitative content analysis. Feasibility was
      assessed by examining participant cooperation rates, instrument completion times,
      item nonresponse, and data yield. RESULTS: Of 47 distinct self-care barriers
      assessed, a median of 15 per patient were indicated as "sometimes" or "often"
      present. Thirty-four specific barriers were reported by more than 25% of patients
      and 9 were reported by more than 50%. The sources of barriers included the
      person, self-care tasks, tools and technologies, and organizational, social, and
      physical contexts. Seven of the top 10 most prevalent barriers were related to
      patient characteristics; the next 3, to the organizational context (eg, life
      disruptions). A preliminary feasibility assessment found few item nonresponses or
      comprehension difficulties, good cooperation, and high data yield from both
      closed- and open-ended items, but also found opportunities to reduce median
      administration time and variability. CONCLUSION: An instrument assessing self
      care barriers from multiple system sources can be feasibly implemented in the ED.
      Further research is required to modify the instrument for widespread use and
      evaluate its implementation across institutions and cultural contexts. Self-care
      barriers measurement can be one component of broader inquiry into the distributed
      health-related "work" activity of patients, caregivers, and clinicians.

PMID- 25616318
TI  - Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and
      Down Syndrome: A Literature Review.
AB  - Pediatric patients with Down syndrome (DS) are at an increased risk of developing
      certain cancers. Specifically, patients with DS have a reported 10-20-fold
      increased risk of developing acute myeloid leukemia (AML). Anthracycline-based
      treatment regimens achieve good results in patients with DS and AML. It has been
      proposed that DS status constitutes a risk factor for the cardiotoxicity
      associated with the use of anthracyclines in the pediatric setting. However,
      published evidence pointing toward an increased risk of cardiotoxicity in
      patients with DS is relatively scarce and conflictive. This concise review
      compiles literature relating to the incidence of anthracycline-related
      cardiotoxicity in pediatric patients with DS. In general, reports from trials
      using anthracyclines at the maximum recommended dose showed increases in the
      incidence of anthracycline-related cardiotoxicity in patients with DS in
      comparison with trials that used anthracyclines at reduced doses. Evidence from
      the literature suggests that patients with DS can achieve favorable therapeutic
      outcomes after receiving treatment with reduced doses of anthracyclines to
      minimize the potential for cardiotoxicity. Further prospective trials, along with
      the available evidence, would assist the design of treatment protocols for
      patients with pediatric leukemias and DS. 

PMID- 25616319
TI  - Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in
      Cardiac Contractility.
AB  - Hydrogen sulfide (H2S) intoxication produces a rapid cardio-circulatory failure
      leading to cardiac arrest. In non-lethal forms of sulfide exposure, the presence
      of a circulatory shock is associated with long-term neurological sequelae. Our
      aim was to clarify the mechanisms of H2S-induced circulatory failure. In
      anesthetized, paralyzed, and mechanically ventilated rats, cardiac output,
      arterial pressure and ventricular pressures were determined while NaHS was
      infused to increase arterial concentration of soluble H2S (CgH2S) from
      undetectable to levels leading to circulatory failure. Compared to control/saline
      infusion, blood pressure started to decrease significantly along with a modest
      drop in peripheral vascular resistance (-19 +/- 5%, P < 0.01), when CgH2S reached
      about 1 MUM. As CgH2S exceeded 2-3 MUM, parameters of ventricular contractility
      diminished with no further reduction in peripheral resistance. Whenever H2S
      exposure was maintained at a higher level (CgH2S over 7 MUM), a severe depression
      of cardiac contractility was observed, leading to asystole within minutes, but
      with no evidence of peripheral vasoplegia. The immediate and long-term
      neurological effects of specifically counteracting sulfide-induced cardiac
      contractility depression following H2S exposure remain to be investigated.

PMID- 25616320
TI  - [Self-adjusting monocanalicular intubation for congenital lacrimal obstruction].
AB  - OBJECTIVE: To present our work with the Masterka self-adjusting monocanalicular
      intubation without nasal recuperation in congenital lacrimal obstruction in
      children over 12-months old. METHODS: A total of 40 children between the ages of
      one and seven (average age 2.6 years) were consecutively operated on. The
      Masterka catheter has a flexible metal guide inside the silicone tube that covers
      it completely. The proximal end is fixed onto the lacrimal punctum by pushing it
      with a dilator or forceps. Its correct position was monitored and visually
      checked in real time during surgery in all cases. RESULTS: The average surgery
      time, excluding anaesthetic, was 1.56min, ranging from 1.05 to 4min. The final
      success was 97.5%, considering absence of epiphora, disappearance of colouring in
      lacrimal meniscus, and mucopurulent secretion. The average follow-up time was 15
      months (ranging from 7 to 21 months). CONCLUSIONS: Masterka intubation is an
      effective primary treatment. It is no more difficult than a simple catheter,
      since the surgical technique is similar, but with better functional results. It
      avoids the possibility of having to repeat the catheterization and it is easier
      to carry out than bicanalicular intubation, since there is no need to manipulate
      repeatedly or use surgical instruments in the inferior meatus, thus simplifying
      the process.

PMID- 25616321
TI  - The prevalence of anemia, iron, vitamin B12, and folic acid deficiencies in
      community dwelling elderly in Ankara, Turkey.
AB  - OBJECTIVE: Anemia is a common problem among older people. Deficiency of essential
      erythropoiesis elements (iron, vitamin B12, and folic acid) is one of the major
      causes of anemia in older people. Studies evaluated prevalence of anemia in our
      country generally consisted of older people admitted to hospital. Studies
      conducted on community dwelling older people were much more less. The aim of this
      study is to evaluate prevalence of anemia and nutritional deficiencies in
      community dwelling elderly in our country. Totally 827 elderly individuals living
      in community participated in this study. MATERIALS AND METHODS: Anemia was
      defined according to the World Health Organization (Hb<13 g/dl for men and Hb<12
      g/dl for women). Iron, vitamin B12, and folic acid deficiencies were evaluated.
      Iron deficiency anemia was diagnosed when anemia with iron level<60 MUg/dl and
      ferritin level<12 ng/ml. Vitamin B12 deficiency anemia was diagnosed when anemia
      with vitamin B12 level<200 pg/ml. Folic acid deficiency anemia was diagnosed when
      anemia with folic acid level<2.6 ng/ml. RESULTS: Prevalence of anemia was found
      7.3%. Prevalence of iron deficiency, vitamin B12, and folic acid deficiency were
      found 7.1%, 64.2% and 10.9%, and 10.9%, respectively. Prevalence of iron
      deficiency anemia was found 2.8%. Prevalence of vitamin B12 deficiency anemia was
      found 4.4% and folic acid deficiency anemia was found 1%. CONCLUSIONS: Prevalence
      of anemia was seen 7.3% in our study, but more studies are needed on anemia in
      community dwelling elderly in our country. Deficiency of iron, vitamin B12, and
      folic acid is also high in Turkey.

PMID- 25616322
TI  - Design, synthesis, and application of OB2C combinatorial peptide and
      peptidomimetic libraries.
AB  - The "one-bead two-compound" (OB2C) combinatorial library is constructed on
      topologically segregated trifunctional bilayer beads such that each bead has a
      fixed cell-capturing ligand and a random library compound co-displayed on its
      surface and a chemical coding tag (bar code) inside the bead. An OB2C library
      containing thousands to millions of compounds can be synthesized and screened
      concurrently within a short period of time. When live cells are incubated with
      such OB2C libraries, every bead will be coated with a monolayer of cells. The
      cell membranes of the captured cells facing the bead surface are exposed to the
      library compounds tethered to each bead. A specific biochemical or cellular
      response can be detected with an appropriate reporter system. The OB2C method
      enables investigators to rapidly discover synthetic molecules that not only
      interact with cell-surface receptors but can also stimulate or inhibit downstream
      cell signaling. To demonstrate this powerful method, one OB2C peptide library and
      two OB2C peptidomimetic libraries were synthesized and screened against Molt-4
      lymphoma cells to discover "death ligands." Apoptosis of the bead-bound cells was
      detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated
      anti-cleaved caspase-3 antibody and 3,3'-diaminobenzidine as a substrate. Two
      novel synthetic "death ligands" against Molt-4 cells were discovered using this
      OB2C library approach. 

PMID- 25616323
TI  - Synthesis of macrocyclic organo-peptide hybrids from ribosomal polypeptide
      precursors via CuAAC-/hydrazide-mediated cyclization.
AB  - Macrocyclic peptides have attracted increasing attention as a potential new
      source of chemical probes and therapeutics. In particular, their conformationally
      restricted structure combined with a high degree of functional and stereochemical
      complexity makes them promising scaffolds for targeting biomolecules with high
      affinity and selectivity. The exploration of this structural class relies on the
      availability of efficient and versatile methods for the generation of large and
      diversified libraries of macrocyclic peptide-based molecules. To this end, we
      have developed a methodology for the synthesis of hybrid organo-peptide
      macrocycles via the cyclization of ribosomally derived polypeptide sequences with
      non-peptidic organic linkers. This strategy relies on the chemoselective and
      bioorthogonal ligation of azide/hydrazide-based "synthetic precursors" with
      intein-fused polypeptides harboring a side-chain alkyne functionality. This
      macrocyclization approach was found to proceed with high efficiency across a
      range of different target peptide sequences spanning 4-12 residues as well as
      across multiple mono- and diaryl-based synthetic precursors. This versatility
      combined with the possibility to integrate non-proteinogenic scaffolds into
      genetically encoded peptide sequences makes this methodology of particularly high
      value toward the creation and screening of highly diverse libraries of peptide
      based macrocycles. 

PMID- 25616324
TI  - Synthesis and screening of one-bead-one-compound cyclic peptide libraries.
AB  - Cyclic peptides have been a rich source of biologically active molecules. Herein
      we present a method for the combinatorial synthesis and screening of large one
      bead-one-compound (OBOC) libraries of cyclic peptides against biological targets
      such as proteins. Up to ten million different cyclic peptides are rapidly
      synthesized on TentaGel microbeads by the split-and-pool synthesis method and
      subjected to a multistage screening protocol which includes magnetic sorting, on
      bead enzyme-linked and fluorescence-based assays, and in-solution binding
      analysis of cyclic peptides selectively released from single beads by
      fluorescence anisotropy. Finally, the most active hit(s) is identified by the
      partial Edman degradation-mass spectrometry (PED-MS) method. This method allows a
      single researcher to synthesize and screen up to ten million cyclic peptides and
      identify the most active ligand(s) in ~1 month, without the time-consuming and
      expensive hit resynthesis or the use of any special equipment. 

PMID- 25616326
TI  - Macrocyclic templates for library synthesis of peptido-conjugates.
AB  - Cyclic peptides have wide utility in the biological sciences. As conformationally
      locked analogs of the parent linear peptides, they possess greater stability
      under physiological conditions and increased binding affinity for their targets.
      As investigations of biological processes often require reporter molecules and
      functional readouts, chemical probes are commonly appended with functional groups
      that allow for conjugation to biological entities. Herein we describe the
      functionalization of cyclic peptides prepared via aziridine aldehyde-mediated
      macrocyclization. These cyclic peptides contain an aziridine ring that can be
      further functionalized by ring opening with nucleophiles. We report on the
      methodology used to produce a cyclic peptide analog of Pro-Gly-Leu-Gly-Phe with
      either azido or sulfhydryl functionality. 

PMID- 25616327
TI  - Synthesis and alkylation of Aza-Gly-Pro building blocks of peptidomimetic
      libraries for developing prostaglandin F2alpha receptor modulators as
      therapeutics to inhibit preterm labor.
AB  - Premature birth is a steadily increasing unmet medical need, for which new
      "tocolytic" agents are required to arrest contractions and delay labor. A peptide
      based approach was developed to produce modulators of the prostaglandin F2alpha
      receptor as a novel target for tocolytic development. In this strategy, the
      solution-phase synthesis and alkylation of aza-glycyl-proline building blocks
      were key for the preparation of a series of modulators exhibiting biased
      signaling. An optimized method is now provided for making the aza-Gly-Pro unit
      with minimum side product, and alkylation of the unit is described to illustrate
      the library diversification step. Conditions have been reported for selectively
      unmasking the protecting groups at the N- and C-terminal of the aza-dipeptide
      unit and for its introduction into analogs that modulate the signaling of the
      PGF2alpha receptor. The merits of this protocol for azapeptide synthesis have
      thus been demonstrated by the synthesis of inhibitors of myometrial contraction
      exhibiting potential as prototypes for developing tocolytics to treat preterm
      labor. 

PMID- 25616325
TI  - Creating site-specific isopeptide linkages between proteins with the traceless
      Staudinger ligation.
AB  - Site-specific isopeptide linkages between the epsilon-amino group of a lysine
      residue in one protein and a carboxyl group in another are central to ubiquitin
      mediated protein degradation and other cellular processes. These linkages are
      inaccessible with common recombinant DNA techniques. Here, we describe a method
      to link two proteins by an authentic isopeptide bond. The method unites three
      techniques at the forefront of molecular biology. An azidonorleucine residue is
      installed at a desired site in a substrate protein by nonnatural amino acid
      incorporation, and a phosphinothioester is installed at the C terminus of a
      pendant protein by expressed protein ligation. Then, the traceless Staudinger
      ligation is used to link the substrate and pendant proteins via an isopeptide
      bond. This method facilitates the study of otherwise intractable protein
      structure-function relationships. 

PMID- 25616328
TI  - A fragment-based selection approach for the discovery of peptide macrocycles
      targeting protein kinases.
AB  - Protein kinases are implicated in diverse signaling cascades and have been
      targeted with small molecules that typically bind the conserved ATP-binding
      active site. These inhibitors are often promiscuous and target multiple protein
      kinases, which has led to the development of alternate strategies to discover
      selective ligands. We have recently described a fragment-based selection
      approach, where a small-molecule warhead can be non-covalently tethered to a
      phage-displayed library of cyclic peptides. This approach led to the conversion
      of the promiscuous kinase inhibitor, staurosporine, into a selective bivalent
      inhibitor. 

PMID- 25616329
TI  - Peptide and peptide library cyclization via bromomethylbenzene derivatives.
AB  - Cyclization confers several advantages to peptides, cumulatively serving to make
      them more drug-like. In this protocol, cyclic peptides are generated via bis
      alkylation of cysteine-containing peptides using alpha,alpha'-dibromo-m-xylene.
      The reactions are robust and high yielding. Multiple reaction platforms for the
      application of this versatile strategy are described herein: the cyclization of
      solid-phase-synthesized peptides, both in solution and on resin, as well as the
      cyclization of in vitro translated mRNA-peptide fusion libraries on oligo(dT)
      resin. 

PMID- 25616330
TI  - Phage selection of bicyclic peptides based on two disulfide bridges.
AB  - Bicyclic peptides can bind with high affinity and selectivity to protein targets,
      making this format attractive for biotechnological and medicinal applications.
      The good binding properties are based to a large extent on the limited
      conformational flexibility of the two connected peptide rings. Bicyclic peptides
      with desired binding specificity can be isolated from phage display libraries
      that are generated by chemically cyclizing linear peptide on phage with
      alkylating reagents. Recently, we presented a strategy for the phage selection of
      bicyclic peptides based on two disulfide bridges. This approach allows the
      generation and screening of topologically highly diverse bicyclic peptide
      structures. Herein, we describe step-by-step protocols to clone and produce
      disulfide-cyclized bicyclic peptide libraries as well as to screen the libraries
      and to synthesize and characterize isolated bicyclic peptides. 

PMID- 25616331
TI  - De novo discovery of bioactive cyclic peptides using bacterial display and flow
      cytometry.
AB  - Cyclic peptides are increasingly desired for their enhanced stability and
      pharmacologic properties. Due to their limited conformational flexibility, cyclic
      peptides with C-to-N-terminal peptide bond and a disulfide bridge can confer high
      target binding affinity and resistance to proteolytic enzymes. Challenging drug
      targets including protein interaction surfaces can be successfully targeted using
      peptides rather than small molecules or proteins. Peptides, capable of antibody
      like affinities with increased potency, can be designed to fill in the gap
      between small molecules and larger proteins. However, cysteine-rich peptides with
      several disulfide bonds have limitations in production and purification.
      Therefore, we devised a strategy to identify cyclic peptides with single
      disulfide connectivity that offers desired properties along with ease in
      synthesis and production. Here, de novo design of cyclic peptides is demonstrated
      through screening of peptide libraries using bacterial display and cell sorting.
      Herein, a step-by-step protocol is presented to design and screen diverse peptide
      libraries to identify cyclic peptides with desired specificity and affinity
      towards arbitrary target proteins. 

PMID- 25616332
TI  - Chemical posttranslational modification of phage-displayed peptides.
AB  - Phage-displayed peptide library has fueled the discovery of novel ligands for
      diverse targets. A new type of phage libraries that displays not only linear and
      disulfide-constrained cyclic peptides but moieties that cannot be encoded
      genetically or incorporated easily by bacterial genetic machinery has emerged
      recently. Chemical posttranslational modification of phage library is one of the
      simplest approaches to encode nonnatural moieties. It confers the library with
      new functionality and makes it possible to select and evolve molecules with
      properties not found in the peptides, for instance, glycopeptides recognized by
      carbohydrate-binding protein and peptides with photoswitching capability. To this
      end, we describe the newly emerging techniques to chemically modify the phage
      library and quantify the efficiency of the reaction with a biotin-capture assay.
      Finally, we provide the methods to construct N-terminal Ser peptide library that
      allows site-selective modification of phage. 

PMID- 25616333
TI  - Mapping protein-protein interactions with phage-displayed combinatorial peptide
      libraries and alanine scanning.
AB  - One avenue for inferring the function of a protein is to learn what proteins it
      may bind to in the cell. Among the various methodologies, one way for doing so is
      to affinity select peptide ligands from a phage-displayed combinatorial peptide
      library and then to examine if the proteins that carry such peptide sequences
      interact with the target protein in the cell. With the protocols described in
      this chapter, a laboratory with skills in microbiology, molecular biology, and
      protein biochemistry can readily identify peptides in the library that bind
      selectively, and with micromolar affinity, to a given target protein on the time
      scale of 2 months. To illustrate this approach, we use a library of bacteriophage
      M13 particles, which display 12-mer combinatorial peptides, to affinity select
      different peptide ligands for two different targets, the SH3 domain of the human
      Lyn protein tyrosine kinase and a segment of the yeast serine/threonine protein
      kinase Cbk1. The binding properties of the selected peptide ligands are then
      dissected by sequence alignment, Kunkel mutagenesis, and alanine scanning.
      Finally, the peptide ligands can be used to predict cellular interacting proteins
      and serve as the starting point for drug discovery. 

PMID- 25616334
TI  - Identifying reactive peptides from phage-displayed libraries.
AB  - Phage display enables the synthesis, selection, and screening of large,
      polypeptide libraries (>1 * 10(10) different members). Selections from such
      libraries can identify binding partners to essentially any desired target
      (Sarikaya et al., Annu Rev Mater Res 34:373-408, 2004; Deutscher, Chem Rev
      110:3196-3211, 2010). Peptides with affinity or reactivity to small molecule
      probes are attractive for numerous uses including the targeted, site-specific
      labeling of proteins. Here, we describe selection and screening protocols for the
      identification of short peptides that can selectively bind to and/or react with
      small molecules. 

PMID- 25616335
TI  - The best and the brightest: exploiting tryptophan-sensitized Tb(3+) luminescence
      to engineer lanthanide-binding tags.
AB  - Consider the lanthanide metals, comprising lanthanum through lutetium.
      Lanthanides form stable cations with a +3 charge, and these ions exhibit a
      variety of useful physical properties (long-lifetime luminescence, paramagnetism,
      anomalous X-ray scattering) that are amenable to studies of biomolecules. The
      absence of lanthanide ions in living systems means that background signals are
      generally a nonissue; however, to exploit the advantageous properties it is
      necessary to engineer a robust lanthanide-binding sequence that can be appended
      to any macromolecules of interest. To this end, the luminescence produced by
      tryptophan-sensitized Tb(3+) has been used as a selection marker for peptide
      sequences that avidly chelate these ions. A combinatorial split-and-pool library
      that uses two orthogonal linkers-one that is cleaved for selection and one that
      is cleaved for sequencing and characterization-has been used to develop
      lanthanide-binding tags (LBTs): peptides of 15-20 amino acids with low-nM
      affinity for Tb(3+). Further validating the success of this screen, knowledge
      about LBTs has enabled the introduction of a lanthanide-binding loop in place of
      one of the four native calcium-binding loops within the protein calcineurin B. 

PMID- 25616336
TI  - Synthesis and cell-based screening of one-bead-one-compound peptide libraries.
AB  - Combinatorial one-bead-one-compound (OBOC) peptide library screening has proven
      to be a powerful tool for identification of small molecules, peptides, or
      peptidomimetics against a variety of specific targets such as cell surface
      receptors, protein kinases, proteases, and phosphatases. With each bead
      displaying many copies of a single chemical entity, millions of compounds can be
      rapidly synthesized and screened with whole-cell binding on-bead functional
      assays. Here we describe the methodology for the synthesis, screening, and
      sequence deconvolution of an OBOC peptide library analyzed for affinity to a
      cancer cell line. 

PMID- 25616337
TI  - Screening peptide array library for the identification of cancer cell-binding
      peptides.
AB  - The identification of cancer cell-specific ligands is a key requirement for the
      targeted delivery of chemotherapeutic agents. Usually phage display system is
      employed to discover cancer-specific peptides through a biopanning process.
      Synthetic peptide array libraries can be used as a complementary method to phage
      display for screening and identifying cancer cell-specific ligands. Here, we
      describe a peptide array-whole cell binding assay to identify cancer cell
      specific peptides. A peptide array library based on a lead dodecapeptide, p160,
      is synthesized on a functionalized cellulose membrane using solid phase chemistry
      and a robotic synthesizer. The relative binding affinity of the peptide library
      is evaluated by incubating the library with fluorescently labeled cancerous or
      non-cancerous cells. Thereby the assay allows picking peptides that show
      selective and high binding to cancerous cells. These peptides represent potential
      candidates for use in cancer-targeted drug delivery, imaging, and diagnosis. 

PMID- 25616338
TI  - Next-generation sequencing of phage-displayed peptide libraries.
AB  - Genetically encoded peptide libraries enabled the discovery of ligands for
      clinically relevant targets and functional materials. Next-generation sequencing
      (NGS) of these libraries improved the selection of ligands by detecting low
      abundant clones and quantifying changes in copy numbers of clones without many
      rounds of selection. Although NGS platforms have been widely used in genome
      assembly, quantification of gene expression (RNA-seq), and metagenomic analyses,
      few examples in the literature describe sequencing phage libraries. This chapter
      aims to provide a detailed method for sequencing a Ph.D.-7 phage display library
      by Ion Torrent. The main techniques covered in this chapter include (1)
      preparation of a phage library for sequencing, (2) sequencing, and (3) analysis
      of the sequencing data by a custom Matlab script. 

PMID- 25616339
TI  - Maleimide-based method for elaboration of cysteine-containing peptide phage
      libraries.
AB  - Peptide-based molecules are known to have therapeutic utility, but the generation
      of phage-focused libraries to optimize peptide properties and functionality is
      challenging. Genetic approaches are limited to peptide extension on the peptide
      termini. Current chemical methods are technically challenging and time-consuming.
      A new chemical method is developed to extend a maleimide-conjugated peptide with
      a cysteine-containing random peptide phage display library. As a proof of
      concept, a 15-mer epidermal growth factor receptor (EGFR)-binding peptide was
      synthesized with a maleimide group at its C-terminus and then conjugated to the
      cysteine-containing library. After panning and screening, several extended
      peptides were discovered and tested to have a higher affinity to EGFR. This
      strategy can have broad utility to optimize pharmacophores of any modalities
      (peptides, unnatural peptides, drug conjugates) capable of bearing a maleimide
      group. 

PMID- 25616340
TI  - Perception of threat and safety at work among employees in the Norwegian
      ministries after the 2011 Oslo bombing.
AB  - BACKGROUND AND OBJECTIVES: Terrorism can heighten fears and undermine the feeling
      of safety. Little is known, however, about the factors that influence threat and
      safety perception after terrorism. The aim of the present study was to explore
      how proximity to terror and posttraumatic stress reactions are associated with
      perceived threat and safety after a workplace terrorist attack. DESIGN AND
      METHODS: A cross-sectional questionnaire survey was administered to employees in
      14 of 17 Norwegian ministries 9-10 months after the 2011 bombing of the
      government headquarters in Oslo (n = 3520). RESULTS: About 198 of 1881 employees
      completing the survey were at work when the bomb exploded. Regression analysis
      showed that this high-exposed group had elevated perceived threat (beta = 0.36;
      95% CI = 0.19 to 0.53) and reduced perceived safety (beta = -0.42; 95% CI = -0.62
      to -0.23) compared to a reference group of employees not at work. After adjusting
      for posttraumatic stress reactions, however, proximity to the explosion no longer
      mattered, whereas posttraumatic stress was associated with both high perceived
      threat (beta = 0.55; 95% CI = 0.48 to 0.63) and low perceived safety (beta = 
      0.71; 95% CI, -0.80 to -0.63). CONCLUSION: Terror-exposed employees feel more
      threatened and less safe after a workplace terrorist attack, and this is closely
      linked to elevated levels of posttraumatic stress reactions.

PMID- 25616341
TI  - Communication and brain.

PMID- 25616343
TI  - Synthesis and biological evaluation of phosphoramidate prodrugs of two analogues
      of 2-deoxy-d-ribose-1-phosphate directed to the discovery of two carbasugars as
      new potential anti-HIV leads.
AB  - 2-Deoxy-alpha-d-ribose-1-phosphate is of great interest as it is involved in the
      biosynthesis and/or catabolic degradation of several nucleoside analogues of
      biological and therapeutic relevance. However due to the lack of a stabilising
      group at its 2-position, it is difficult to synthesize stable prodrugs of this
      compound. In order to overcome this lack of stability, the synthesis of
      carbasugar analogues of 2-deoxyribose-1-phosphate was envisioned. Herein the
      preparation of a series of prodrugs of two carbocyclic analogues of 2-deoxyribose
      1-phosphate using the phosphoramidate ProTide technology, along with their
      biological evaluation against HIV and cancer cell proliferation, is reported. 

PMID- 25616342
TI  - Predicting genome-wide DNA methylation using methylation marks, genomic position,
      and DNA regulatory elements.
AB  - BACKGROUND: Recent assays for individual-specific genome-wide DNA methylation
      profiles have enabled epigenome-wide association studies to identify specific CpG
      sites associated with a phenotype. Computational prediction of CpG site-specific
      methylation levels is critical to enable genome-wide analyses, but current
      approaches tackle average methylation within a locus and are often limited to
      specific genomic regions. RESULTS: We characterize genome-wide DNA methylation
      patterns, and show that correlation among CpG sites decays rapidly, making
      predictions solely based on neighboring sites challenging. We built a random
      forest classifier to predict methylation levels at CpG site resolution using
      features including neighboring CpG site methylation levels and genomic distance,
      co-localization with coding regions, CpG islands (CGIs), and regulatory elements
      from the ENCODE project. Our approach achieves 92% prediction accuracy of genome
      wide methylation levels at single-CpG-site precision. The accuracy increases to
      98% when restricted to CpG sites within CGIs and is robust across platform and
      cell-type heterogeneity. Our classifier outperforms other types of classifiers
      and identifies features that contribute to prediction accuracy: neighboring CpG
      site methylation, CGIs, co-localized DNase I hypersensitive sites, transcription
      factor binding sites, and histone modifications were found to be most predictive
      of methylation levels. CONCLUSIONS: Our observations of DNA methylation patterns
      led us to develop a classifier to predict DNA methylation levels at CpG site
      resolution with high accuracy. Furthermore, our method identified genomic
      features that interact with DNA methylation, suggesting mechanisms involved in
      DNA methylation modification and regulation, and linking diverse epigenetic
      processes.

PMID- 25616344
TI  - Arteether resistance reversal by ketoconazole/fluconazole in rodent malaria
      parasite Plasmodium vinckei.
AB  - Artemisinin and its derivative arteether (ART) are fast acting antimalarial drugs
      against chloroquine-resistant. There are several partner drugs that are
      identified as a potential drug for artemisinin combination therapy (ACT) to
      develop as the antimalarial drug. Limited studies have been carried out in ART
      drug combination that may have more promising as ACT for resistant Plasmodium
      parasite. Here, we are the first to show the ART drug resistance reversal in
      Plasmodium vinckei by using antifungal azole compounds ketoconazole (KTZ) and
      fluconazole (FCZ). Our previous study has shown that higher antioxidant enzyme,
      glutathione, and less hemozoin may be correlated with ART resistance in P.
      vinckei (PvAR). We further hypothesized that glutathione and heme catabolism may
      be interfered by KTZ and FCZ, resulting in an increased efficacy of ART in PvAR
      parasite. The results of present study demonstrate synergetic effect of KTZ and
      FCZ against PvAR parasite, since none of the mice developed infection up to day
      10 after combination with ART. These results further showed that ED90 of ART was
      reduced from 17.23 to 2.19 and 2.56 mg/kg when used in combination with KTZ and
      FCZ, respectively. Resultant, activity enhancement index (AEI) of ART is
      significantly increased to 8.60 and 6.73 with partner agents. These studies
      propose the possibility of ART drug combination that may be helpful in prolonging
      the life of drug and a promising lead to reduce the chance of resistance
      development of artemisinin and its derivative.

PMID- 25616345
TI  - Salpingectomy and proximal tubal occlusion for hydrosalpinx prior to in vitro
      fertilization: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The objective of this study was to conduct a systematic review of
      studies comparing the pregnancy outcomes in hydrosalpinx patients treated with
      salpingectomy versus those treated with proximal tubal occlusion prior to in
      vitro fertilization (IVF). DATA SOURCES: An extensive PubMed literature search
      was performed for the period from 1980 to December 2013 using combinations of the
      following keywords: "hydrosalpinx," "salpingectomy," and "tubal occlusion."
      METHODS OF THE STUDY SELECTION: Initially, 204 relevant studies were identified
      from MEDLINE and screened for retrieval. All of the randomized controlled trials
      comparing ovarian response and the pregnancy outcome of salpingectomy and
      proximal tubal occlusion for hydrosalpinx patients prior to IVF were considered
      eligible for analysis. TABULATION, INTEGRATION, AND RESULTS: Two investigators
      independently reviewed the studies. The data were pooled, and the mean standard
      difference (SD) was calculated. Eligible randomized controlled trials were
      selected for this meta-analysis. There were no differences in the response days
      to controlled ovarian hyperstimulation (SD = -1.112, SE = 0.973, Z = -1.14, P =
      0.253), number of oocytes retrieved (SD = 0.404, SE = 0.311, Z = 1.300, P =
      0.194), embryos transferred per cycle (SD = -0.757, SE = 0.568, Z = -1.332, P =
      0.183), and fertilized oocytes (SD = -0.006, SE = 0.130, Z = -0.045, P = 0.964)
      between the patients receiving salpingectomy and proximal tubal occlusion. The
      pooled rates for clinical pregnancy (odds ratio, 0.864; 95% confidence interval,
      0.534-1.398; Z = -0.596, P = 0.551) and implantation (odds ratio, 1.558; 95%
      confidence interval, 0.809-3.003; Z = 1.325, P = 0.185) were not significantly
      different between the hydrosalpinx patients with salpingectomy versus proximal
      tubal occlusion. CONCLUSIONS: Similar responses to controlled ovarian
      hyperstimulation and pregnancy outcome were observed in patients treated with
      salpingectomy or proximal tubal occlusion.

PMID- 25616346
TI  - Breaking bad news to a pregnant woman with a fetal abnormality on ultrasound.
AB  - Ultrasound is a common procedure performed in pregnancy. Most obstetric patients
      have an ultrasound between 18 and 20 weeks' gestation. While there is debate
      regarding the utility of this ultrasound, it has become a routine part of
      prenatal care. Discovery of a fetal anomaly on ultrasound is most commonly an
      unexpected, emotionally devastating event for pregnant women. Counseling these
      women about the ultrasound findings requires empathy and sensitivity. This task
      falls on the physicians caring for pregnant women: maternal-fetal medicine
      specialists, radiologists, generalist obstetricians, and family medicine
      physicians. Their training regarding breaking bad news is varied. Therefore, the
      purpose of this article is to provide a framework to break bad news of an
      anomalous fetus for physicians caring for pregnant women using the SPIKES
      protocol. The SPIKES acronym stands for setting, perception, invitation,
      knowledge, empathize, summary, and strategy. 

PMID- 25616347
TI  - In vitro maturation and its role in clinical assisted reproductive technology.
AB  - IMPORTANCE: In vitro maturation (IVM) refers to maturation in culture of immature
      oocytes that may or may not have been exposed to short courses of gonadotropins.
      Approximately 5000 live births have occurred as a result of IVM since the 1970s.
      Currently, IVM is reserved for carefully selected patients at risk for ovarian
      hyperstimulation syndrome and for those with contraindications to hormone
      administration. The technology is still considered experimental. OBJECTIVE: The
      objective of this study was to identify a role for IVM and discuss clinical
      practices based on the current literature. EVIDENCE ACQUISITION: We conducted a
      literature review of all available and published data. Relevant studies were
      identified using PubMed and MEDLINE. Search parameters included "in vitro
      maturation or IVM" and "oocyte maturation." Multiple case-control studies were
      identified comparing reproductive outcomes between conventional in vitro
      fertilization (IVF) and IVM, but no randomized controlled trials have been
      reported to date comparing IVF and IVM. RESULTS: Results from retrospective and
      prospective observational studies have shown decreased live birth and
      implantation rates in comparison to conventional IVF/intracytoplasmic sperm
      injection for patients with various indications for IVM. However, rates of
      ovarian hyperstimulation syndrome were significantly reduced in studies with
      patients with polycystic ovary syndrome. CONCLUSIONS: Although the pregnancy rate
      is lower than conventional IVF, IVM is a safer and simpler alternative to
      conventional IVF. Future research needs to focus on improving implantation and
      live birth rates before universal implementation.

PMID- 25616348
TI  - Prevalence and outcome of lung cancer in lung transplant recipients.
AB  - BACKGROUND: Lung transplant is the only available therapy for patients with
      advanced lung disease. The goal of this study was to examine the prevalence,
      origin, management and outcome of lung cancer in recipients of lung transplant at
      our institution. METHODS: After institutional review board approval, we conducted
      a retrospective chart review of all lung transplantations in our institution from
      January 1990 until June 2012. RESULTS: The prevalence of lung cancer in the
      explanted lung was 6 (1.2%) of 462 and all cases were in subjects with lung
      fibrosis. All 4 subjects with lymph node involvement died of causes related to
      the malignancy. Nine (1.9%) of 462 patients were found to have bronchogenic
      carcinoma after lung transplant. The most common location was in the native lung
      in recipients of a single lung transplant (6 out of 9 patients). In one case, the
      tumor originated in the allograft and was potentially donor related. The median
      time to diagnosis after lung transplant was 28 months with a range from 9 months
      to 10 years. Median survival was 8 months, with tumors involving lymph nodes or
      distant metastases associated with a markedly worse prognosis (median survival 7
      months) than stage I disease (median survival 27 months). CONCLUSIONS: The
      prevalence of lung cancer in lung transplant recipients is low. Using accepted
      donor screening criteria, donor derived malignancy is exceptionally rare. While
      stage I disease is associated with improved survival in this cohort, survival is
      still not comparable to that of the general population, likely influenced by the
      need for aggressive immune suppression.

PMID- 25616349
TI  - Pedicle screw loosening: a clinically relevant complication?
AB  - PURPOSE: Literature studies showed a very wide range of pedicle screw loosening
      rates after thoracolumbar stabilization, ranging from less than 1 to 15 % in non
      osteoporotic patients treated with rigid systems and even higher in osteoporotic
      subjects or patients treated with dynamic systems. Firstly, this paper aims to
      investigate how much this complication is affecting the success rate of pedicle
      screw fixation, in both non-osteoporotic and osteoporotic patients, and to
      discuss the biomechanical reasons which may be related to the variability of the
      rates found in the literature. The secondary aim was to summarize and discuss the
      published definitions and conventions about screw loosening from a clinical and
      radiological point of view. METHODS: Narrative literature review. RESULTS: Screw
      loosening appears to be a minor problem for fixation and fusion of healthy, non
      osteoporotic bone. Pedicle screw fixation in osteoporotic bone is believed to be
      at risk of loosening, but clinical data are actually scarce. Both expandable and
      augmented screws may be a viable option to reduce the risk of loosening, but
      clinical evidence is missing. Posterior motion-preserving implants seems to have
      a significant risk of screw loosening. Standardization appears to be lacking
      regarding the radiological assessment. Marked differences in the loosening rates
      found based either on planar radiography or on CT scanning were observed.
      CONCLUSIONS: Reported loosening rates primarily depended on the protocol used for
      the clinical examination during follow-up and on the conventions used for the
      radiological assessment. Aiming to a better comparability of published data, we
      recommend the authors of clinical studies to describe which criteria were used to
      assess a loosened screw, as well as the protocol of the clinical follow-up
      examination. Low-dose CT should be used for the assessment of screw loosening
      whenever possible.

PMID- 25616350
TI  - Air cholangiogram is not inferior to dye cholangiogram for malignant hilar
      biliary obstruction: a randomized study of efficacy and safety.
AB  - BACKGROUND: Endoscopic biliary drainage is the palliative treatment of choice in
      patients with malignant hilar biliary obstruction. Contrast injection can lead to
      cholangitis, whereas air cholangiography may have a lesser incidence of
      cholangitis. OBJECTIVE: The objective of the present study is to prospectively
      compare the efficacy and safety of air vs. dye cholangiogram in malignant hilar
      biliary obstruction. METHODS: Patients with type II and III malignant hilar
      biliary stricture were included in a prospectively randomized manner at a
      tertiary care center. Unilateral self-expanding metal stent was placed in
      patients with a malignant hilar block using either air or dye as a contrast
      medium. Outcome measures were successful deployment, successful drainage, early
      complications, and procedure-related and 30-day mortality. RESULTS: Forty-nine
      patients were randomized to air cholangiogram (25 patients, group A) or dye
      cholangiogram (24 patients, group B). Most of the patients had type II stricture
      (19 in group A and 20 in group B). Successful stenting and drainage were achieved
      in 25 (100 %) and 24 (96 %) in group A and 23 (95.8 %) and 22 (91.6 %) (p = ns),
      respectively. Cholangitis developed in 1 (4 %) and 4 (16.6 %) in group A and B,
      respectively (p < 0.05). There was no procedure-related or 30-day mortality.
      CONCLUSION: Use of air cholangiography was as safe and as effective as dye
      cholangiography in patients with malignant hilar biliary obstruction, and it
      decreased the risk of post-ERCP cholangitis.

PMID- 25616351
TI  - Evaluation of noncardiac chest pain in Indian setting--can we reduce the
      investigation burden?

PMID- 25616352
TI  - Predictors of sentinel lymph node status in cutaneous melanoma: a classification
      and regression tree analysis.
AB  - OBJECTIVE: The main aim of this study was to identify predictors of sentinel
      lymph node (SN) metastasis in cutaneous melanoma. PATIENTS AND METHODS: This was
      a retrospective cohort study of 818 patients in 2 tertiary-level hospitals. The
      primary outcome variable was SN involvement. Independent predictors were
      identified using multiple logistic regression and a classification and regression
      tree (CART) analysis. RESULTS: Ulceration, tumor thickness, and a high mitotic
      rate (>=6 mitoses/mm(2)) were independently associated with SN metastasis in the
      multiple regression analysis. The most important predictor in the CART analysis
      was Breslow thickness. Absence of an inflammatory infiltrate, patient age, and
      tumor location were predictive of SN metastasis in patients with tumors thicker
      than 2mm. In the case of thinner melanomas, the predictors were mitotic rate (>6
      mitoses/mm(2)), presence of ulceration, and tumor thickness. Patient age, mitotic
      rate, and tumor thickness and location were predictive of survival. CONCLUSIONS:
      A high mitotic rate predicts a higher risk of SN involvement and worse survival.
      CART analysis improves the prediction of regional metastasis, resulting in better
      clinical management of melanoma patients. It may also help select suitable
      candidates for inclusion in clinical trials.

PMID- 25616353
TI  - Characterization of medical students recall of factual knowledge using learning
      objects and repeated testing in a novel e-learning system.
AB  - BACKGROUND: Spaced-repetition and test-enhanced learning are two methodologies
      that boost knowledge retention. ALERT STUDENT is a platform that allows creation
      and distribution of Learning Objects named flashcards, and provides insight into
      student judgments-of-learning through a metric called 'recall accuracy'. This
      study aims to understand how the spaced-repetition and test-enhanced learning
      features provided by the platform affect recall accuracy, and to characterize the
      effect that students, flashcards and repetitions exert on this measurement.
      METHODS: Three spaced laboratory sessions (s0, s1 and s2), were conducted with
      n=96 medical students. The intervention employed a study task, and a quiz task
      that consisted in mentally answering open-ended questions about each flashcard
      and grading recall accuracy. Students were randomized into study-quiz and quiz
      groups. On s0 both groups performed the quiz task. On s1 and s2, the study-quiz
      group performed the study task followed by the quiz task, whereas the quiz group
      only performed the quiz task. We measured differences in recall accuracy between
      groups/sessions, its variance components, and the G-coefficients for the
      flashcard component. RESULTS: At s0 there were no differences in recall accuracy
      between groups. The experiment group achieved a significant increase in recall
      accuracy that was superior to the quiz group in s1 and s2. In the study-quiz
      group, increases in recall accuracy were mainly due to the session, followed by
      flashcard factors and student factors. In the quiz group, increases in recall
      accuracy were mainly accounted by flashcard factors, followed by student and
      session factors. The flashcard G-coefficient indicated an agreement on recall
      accuracy of 91% in the quiz group, and of 47% in the study-quiz group.
      CONCLUSIONS: Recall accuracy is an easily collectible measurement that increases
      the educational value of Learning Objects and open-ended questions. This metric
      seems to vary in a way consistent with knowledge retention, but further
      investigation is necessary to ascertain the nature of such relationship. Recall
      accuracy has educational implications to students and educators, and may
      contribute to deliver tailored learning experiences, assess the effectiveness of
      instruction, and facilitate research comparing blended-learning interventions.

PMID- 25616354
TI  - Viral transduction of the HER2-extracellular domain expands trastuzumab-based
      photoimmunotherapy for HER2-negative breast cancer cells.
AB  - The prognosis of HER2-positive breast cancer has been improved by trastuzumab
      therapy, which features high specificity and limited side effects. However,
      trastuzumab-based therapy has shortcomings. Firstly, HER2-targeted therapy is
      only applicable to HER2-expressing tumors, which comprise only 20-25% of primary
      breast cancers. Secondly, many patients who initially respond to trastuzumab
      ultimately develop disease progression. To overcome these problems, we employed
      virus-mediated HER2 transduction and photoimmunotherapy (PIT) which involves
      trastuzumab conjugated with a photosensitizer, trastuzumab-IR700, and irradiation
      of near-infrared light. We hypothesized that the gene transduction technique
      together with PIT would expand the range of tumor entities suitable for
      trastuzumab-based therapy and improve its antitumor activity. The HER2
      extracellular domain (ECD) was transduced by the adenoviral vector, Ad-HER2-ECD,
      and PIT with trastuzumab-IR700 was applied in the HER2-negative cancer cells. Ad
      HER2-ECD can efficiently transduce HER2-ECD into HER2-negative human cancer
      cells. PIT with trastuzumab-IR700 induced direct cell membrane destruction of Ad
      HER2-ECD-transduced HER2-negative cancer cells. Novel combination of viral
      transduction of a target antigen and an antibody-based PIT would expand and
      potentiate molecular-targeted therapy even for target-negative or attenuated
      cancer cells.

PMID- 25616356
TI  - RETRACTED ARTICLE: Enhancement of doxorubicin efficacy through suppression of
      serine synthesis in triple-negative breast cancer.

PMID- 25616355
TI  - The prognostic and predictive value of Tregs and tumor immune subtypes in
      postmenopausal, hormone receptor-positive breast cancer patients treated with
      adjuvant endocrine therapy: a Dutch TEAM study analysis.
AB  - Evidence exists for an immunomodulatory effect of endocrine therapy in hormone
      receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study
      was to define the prognostic and predictive value of tumor immune markers and the
      tumor immune profile in HR+ve BC, treated with different endocrine treatment
      regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant
      hormonal treatment, randomly assigned to different regimens: 5 years of
      exemestane or sequential treatment (2.5 years of tamoxifen-2.5 years of
      exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G,
      and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune
      susceptible) were determined by the effect size of mono-immune markers on relapse
      rate. Patients on sequential treatment with high level of tumor-infiltrating
      FoxP3+ cells had significant (p = 0.019, HR 0.729, 95% CI 0.560-0.949) better OS.
      Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS
      p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine
      treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95% CI 0.878-2.297;
      HR low IS 1.657, 95% CI 1.131-2.428; BCSS: p = 0.002, HR intermediate IS 2.486,
      95% CI 1.375-4.495; HR low IS 2.422, 95% CI 1.439-4.076; and OS: p = 0.005, HR
      intermediate IS 1.509, 95% CI 0.950-2.395; HR low IS 1.848, 95% CI 1.277-2.675).
      Tregs and the tumor IS presented in this study harbor prognostic value for
      sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for
      solely exemestane-treated patients. Therefore, these markers could be used as a
      clinical risk stratification tool to guide adjuvant treatment in this BC
      population.

PMID- 25616358
TI  - [Chirurgie de la main: a journal in English for French hand surgeons, and much
      more].

PMID- 25616357
TI  - Acid sphingomyelinase inhibition protects mice from lung edema and lethal
      Staphylococcus aureus sepsis.
AB  - Pulmonary edema associated with increased vascular permeability is a severe
      complication of Staphylococcus aureus-induced sepsis and an important cause of
      human pathology and death. We investigated the role of the mammalian acid
      sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by
      S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic
      inhibition of Asm reduced lung edema in mice infected with S. aureus. The
      Asm/ceramide system triggered the formation of superoxide, resulting in
      degradation of tight junction proteins followed by lung edema. Treatment of
      infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from
      lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In
      turn, treatment with antibiotics reduced bacterial numbers but did not protect
      mice from lung edema. In contrast, only the combination of antibiotics and
      amitriptyline inhibited both pulmonary edema and bacteremia protecting mice from
      lethal sepsis and lung dysfunction suggesting the combination of both drugs as
      novel treatment option for sepsis. KEY MESSAGES: Antibiotics are often
      insufficient to cure S. aureus-induced sepsis. S. aureus induces lung edema via
      the Asm/ceramide system. Genetic deficiency of Asm inhibits lung dysfunction upon
      infection with S. aureus. Pharmacologic inhibition of Asm reduces lung edema
      induced by S. aureus. Antibiotics plus amitriptyline protect mice from lung edema
      and lethal S. aureus sepsis.

PMID- 25616359
TI  - [Demography and age-dependency in ophthalmic diseases].
AB  - This article explains key terms in demography and describes current and future
      changes in the composition of the German population. The ratio of older persons
      is greatly increasing as age groups from higher birth rates are growing older and
      as the life expectancy continues to rise particularly for older age groups.
      Ophthalmology is highly affected by these societal changes as eye diseases
      particularly affect the elderly. The prevalence of blindness and low vision is
      increasing in the older population even though this increase is being overlapped
      by a general reduction in the risk of blindness. Up to more than 30% more age
      related eye diseases are expected in the population by the year 2030, which will
      lead to an additional roughly 7.7 million ophthalmic consultations in the
      population of more than 60 years of age. The healthcare units need to be adjusted
      to the rising demand for ophthalmic care.

PMID- 25616360
TI  - Memory and selective attention in multiple sclerosis: cross-sectional computer
      based assessment in a large outpatient sample.
AB  - Cognitive impairments may have a severe impact on everyday functioning and
      quality of life of patients with multiple sclerosis (MS). However, there are some
      methodological problems in the assessment and only a few studies allow a
      representative estimate of the prevalence and severity of cognitive impairments
      in MS patients. We applied a computer-based method, the memory and attention test
      (MAT), in 531 outpatients with MS, who were assessed at nine neurological
      practices or specialized outpatient clinics. The findings were compared with
      those obtained in an age-, sex- and education-matched control group of 84 healthy
      subjects. Episodic short-term memory was substantially decreased in the MS
      patients. About 20% of them reached a score of only less than two standard
      deviations below the mean of the control group. The episodic short-term memory
      score was negatively correlated with the EDSS score. Minor but also significant
      impairments in the MS patients were found for verbal short-term memory, episodic
      working memory and selective attention. The computer-based MAT was found to be
      useful for a routine assessment of cognition in MS outpatients.

PMID- 25616361
TI  - Childhood sarcoidosis: Louisiana experience.
AB  - A retrospective chart review was conducted to detect patients with sarcoidosis
      seen by pediatric rheumatology service from the period of 1992 to 2013 at
      Children's hospital of New Orleans. Twenty-seven patients were identified. The
      average duration of symptoms before diagnosis was 5 (range 1-120) months. Five
      patients had onset before the age of 5 years and were diagnosed with early-onset
      sarcoidosis. The most common manifestations at presentation were constitutional
      symptoms (62 %) followed by ocular (38 %). During the course of illness, 19/27
      (70 %) had multiorgan involvement. Common manifestations included uveitis/iritis
      (77 %), fever (50 %), hilar adenopathy (42 %), arthritis (31 %), peripheral
      lympadenopathy (31 %), hepatosplenomegaly (31 %), parenchymal lung disease (27
      %), and skin rash (19 %). Unusual manifestations included granulomatous bone
      marrow disease (3 cases), hypertension (2), abdominal aortic aneurysm (large
      vessel vasculitis; 1), granulomatous hepatitis (1), nephrocalcinosis (1),
      membranous nephropathy (1), refractory granulomatous interstitial nephritis with
      recurrence in transplanted kidney (1), CNS involvement (2), parotid gland
      enlargement (1), and sensorineural hearing loss (1). Biopsy specimen was obtained
      in 21/27 (77 %) patients, and demonstration of noncaseating granuloma associated
      with negative stains for mycobacteria and fungi was seen in 18 patients. Elevated
      angiotensin-converting enzyme level was seen in 74 % of patients. Treatment with
      oral prednisone was initiated in symptomatic patients with significant clinical
      improvement. Low-dose methotrexate (MTX) 10-15 mg/m(2)/week orally, as steroid
      sparing agent, was administered in 14 patients. Other immunomodulators included
      cyclophosphamide (2 patients), etanercept (2), infliximab (2), mycophenolate
      mofetil (1), and tacrolimus (1). Childhood sarcoidosis is prevalent in Louisiana.
      Most of the affected children present with a multisystem disease associated with
      manifestations similar to those of adult patients. Low-dose MTX seems to be
      effective, steroid sparing, and safe adjunct to treat sarcoidosis with multiorgan
      involvement. Early-onset disease is less common and associated with increased
      morbidity, flares, and poor prognosis. 

PMID- 25616363
TI  - Knee kinetics and kinematics: What are the effects of TKA malconfigurations?
AB  - PURPOSE: Total knee arthroplasty (TKA) is a very successful surgical procedure.
      However, implant failures and patient dissatisfaction still persist. Sometimes
      surgeons are not able to understand and explain these negative performances
      because the patient's medical images "look good", but the patient "feels bad".
      Apart from radiograph imaging and clinical outcome scores, conventionally used
      follow-up methods are mainly based on the analysis of knee kinematics. However,
      even if kinematics remains close to the "normal" range of motion, the patient may
      still complain about pain and functional limitations. To provide more insight
      into this paradox, a better quantitative understanding of TKA mechanics must be
      developed. For this purpose, improved techniques for clinical follow-up,
      combining kinetics and kinematics analysis, should be introduced to help surgeons
      to assess and understand TKA performance. METHODS: An analysis on four TKA
      designs was performed, and the changes in kinematics and in kinetics induced by
      several implant configurations (simulating implant malalignment and different
      knee anatomy) were compared. More specifically, analysed tibio-femoral and
      patello-femoral contact forces and tibio-femoral kinematics were analysed during
      a squat task up to 120 degrees . RESULTS: The results from this study show that
      contact forces (with changes up to 67 %) are more heavily affected by
      malconfigurations than kinematics, for which maximum deviations are of the order
      of 5 mm or 5 degrees , similar to the simulated surgical errors. The results
      present a similar trend for the different designs. CONCLUSIONS: The results
      confirm the hypothesis that kinematics is not the only and also not the most
      relevant parameter to predict or explain knee function after TKA. In the future,
      techniques to analyse knee kinetics should be integrated in the clinical follow
      up.

PMID- 25616364
TI  - Improved abdominal MRI in non-breath-holding children using a radial k-space
      sampling technique.
AB  - BACKGROUND: Radial k-space sampling techniques have been shown to reduce motion
      artifacts in adult abdominal MRI. OBJECTIVE: To compare a T2-weighted radial k
      space sampling MRI pulse sequence (BLADE) with standard respiratory-triggered T2
      weighted turbo spin echo (TSE) in pediatric abdominal imaging. MATERIALS AND
      METHODS: Axial BLADE and respiratory-triggered turbo spin echo sequences were
      performed without fat suppression in 32 abdominal MR examinations in children. We
      retrospectively assessed overall image quality, the presence of respiratory,
      peristaltic and radial artifact, and lesion conspicuity. We evaluated signal
      uniformity of each sequence. RESULTS: BLADE showed improved overall image quality
      (3.35 +/- 0.85 vs. 2.59 +/- 0.59, P < 0.001), reduced respiratory motion artifact
      (0.51 +/- 0.56 vs. 1.89 +/- 0.68, P < 0.001), and improved lesion conspicuity
      (3.54 +/- 0.88 vs. 2.92 +/- 0.77, P = 0.006) compared to respiratory triggering
      turbo spin-echo (TSE) sequences. The bowel motion artifact scores were similar
      for both sequences (1.65 +/- 0.77 vs. 1.79 +/- 0.74, P = 0.691). BLADE introduced
      a radial artifact that was not observed on the respiratory triggering-TSE images
      (1.10 +/- 0.85 vs. 0, P < 0.001). BLADE was associated with diminished signal
      variation compared with respiratory triggering-TSE in the liver, spleen and air
      (P < 0.001). CONCLUSION: The radial k-space sampling technique improved the
      quality and reduced respiratory motion artifacts in young children compared with
      conventional respiratory-triggered turbo spin-echo sequences.

PMID- 25616362
TI  - Pseudouridine: still mysterious, but never a fake (uridine)!
AB  - Pseudouridine (Psi) is the most abundant of >150 nucleoside modifications in RNA.
      Although Psi was discovered as the first modified nucleoside more than half a
      century ago, neither the enzymatic mechanism of its formation, nor the function
      of this modification are fully elucidated. We present the consistent picture of
      Psi synthases, their substrates and their substrate positions in model organisms
      of all domains of life as it has emerged to date and point out the challenges
      that remain concerning higher eukaryotes and the elucidation of the enzymatic
      mechanism. 

PMID- 25616365
TI  - Hickman line fracture in a road traffic accident.

PMID- 25616367
TI  - Ser245Tyr TINF2 mutation in a long-term survivor after a second myeloablative SCT
      following late graft failure for Aplastic Anaemia.

PMID- 25616366
TI  - Pharmacophore modeling improves virtual screening for novel peroxisome
      proliferator-activated receptor-gamma ligands.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear hormone
      receptor involved in regulating various metabolic and immune processes. The PPAR
      family of receptors possesses a large binding cavity that imparts promiscuity of
      ligand binding not common to other nuclear receptors. This feature increases the
      challenge of using computational methods to identify PPAR ligands that will dock
      favorably into a structural model. Utilizing both ligand- and structure-based
      pharmacophore methods, we sought to improve agonist prediction by grouping
      ligands according to pharmacophore features, and pairing models derived from
      these features with receptor structures for docking. For 22 of the 33 receptor
      structures evaluated we observed an increase in true positive rate (TPR) when
      screening was restricted to compounds sharing molecular features found in
      rosiglitazone. A combination of structure models used for docking resulted in a
      higher TPR (40 %) when compared to docking with a single structure model (<20 %).
      Prediction was also improved when specific protein-ligand interactions between
      the docked ligands and structure models were given greater weight than the
      calculated free energy of binding. A large-scale screen of compounds using a
      marketed drug database verified the predictive ability of the selected structure
      models. This study highlights the steps necessary to improve screening for
      PPARgamma ligands using multiple structure models, ligand-based pharmacophore
      data, evaluation of protein-ligand interactions, and comparison of docking
      datasets. The unique combination of methods presented here holds potential for
      more efficient screening of compounds with unknown affinity for PPARgamma that
      could serve as candidates for therapeutic development.

PMID- 25616368
TI  - Association of abnormal erythrocyte morphology with oxidative stress and
      inflammation in metabolic syndrome.
AB  - In carrying out their role of free radical scavenging, erythrocytes become
      damaged due to oxidation of membrane lipids and proteins. Such damage may change
      the morphology of the erythrocytes. The present study aims to demonstrate change
      in erythrocyte morphology in MetS and associate the changes with increased
      oxidative stress and inflammation that were shown in our recent study. One
      hundred participants were recruited from a rural town of Australia. Whole blood
      viscosity, erythrocyte aggregation, erythrocyte deformability, lipid profile and
      blood sugar level, oxidative stress markers (erythrocyte reduced glutathione,
      superoxide dismutase, urinary isoprostanes) and inflammatory markers (high
      sensitivity C-reactive protein) were measured. Erythrocyte morphological study
      was performed by scanning electron microscopy. Recruited participants were
      classified into MetS and non-MetS following the National Cholesterol Education
      Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20
      software. The mean percentages of biconcave cells were decreased whereas
      acanthocytes, stomatocytes and echinocytes were increased in MetS group compared
      to healthy controls. Morphologically abnormal erythrocytes were significantly
      correlated with oxidative stress and chronic inflammation markers. Free radicals
      generated in increased concentration in MetS seem to damage erythrocyte changing
      its morphology which possibly could affect other hemorheological parameters. 

PMID- 25616369
TI  - High glucose-induced human cellular immune response is governed by miR-2909
      RNomics.
AB  - Regulation of NFkB family member RelA translocation by tumour suppressor genes
      encoding p53 and KLF4, has been widely recognized as the critical for human
      peripheral blood mononuclear cells (PBMCs) to meet their energy requirement for
      tailoring their immune response against any perceived threat. Our study was
      addressed to understand as to how human PBMCs respond to high glucose threat in
      terms of their genomics-directed immune response. The results of such a study
      revealed for the first time that NFkB induced miR-2909 RNomics is crucial for the
      regulation of RelA translocation within human PBMCs exposed to high glucose
      thereby enabling these epigenetically programmed cells to tailor immune response
      involving genes coding for CCL5; IFN-gamma and IL-17. Based upon these results an
      attempt was also made to propose a mechanistic pathway that links high glucose
      induced cellular miR-2909 RNomics with the genes involved in energy metabolism
      and immune response. 

PMID- 25616370
TI  - Monitoring and Alleviation of Symptom Occurrence and Severity Among Thai Children
      and Adolescents During Cancer Treatments.
AB  - BACKGROUND: Symptom monitoring and alleviation are important during pediatric
      cancer treatments. AIMS: To examine the use of the Therapy-Related Symptom
      Checklist for Children (TRSC-C; Thai version) for reported occurrence, severity,
      and management of treatment-related symptoms within a cohort of Thai pediatric
      oncology patients/parents METHOD: Cross-sectional study; convenience sample: 100
      parents of 71 male children/29 females, 63% with leukemia, 37%, other diagnoses;
      age-groups: <5 years, n = 33; 5 to 11 years, n = 44; 12 to 17 years, n = 25.
      Parents reported children's symptom occurrence/severity on the TRSC-C; and
      complementary care methods on the Symptom Alleviation: Self-Care Methods and
      their symptom alleviation methods. All tools had good psychometric properties.
      RESULTS: 18 symptoms on the 30-item TRSC-C occurred in 42% to 95% of children.
      Mean severity of symptoms was between 1.0 ("a bit") and 2.0 ("quite a bit"); 5
      month to 11-year-old children had higher (worse) TRSC-C total scores.
      Complementary care was used and reported. CONCLUSIONS: Monitoring of multiple
      symptoms with the TRSC-C and parental symptom alleviation helped children.
      CLINICAL IMPLICATIONS: Thai parents/patients need and accept assistance in
      monitoring/managing side effects of pediatric cancer therapy.

PMID- 25616371
TI  - Health-Related Quality of Life of Adolescent and Young Adult Survivors of Central
      Nervous System Tumors: Identifying Domains From a Survivor Perspective.
AB  - This article uses qualitative methods to describe the domains of health-related
      quality of life (HRQoL) that adolescent and young adult (AYA) survivors of
      central nervous system (CNS) tumors identify as important. Survivors clearly
      attributed aspects of their current HRQoL to their disease or its treatment. We
      identified 7 key domains of AYA CNS tumor survivorship: physical health, social
      well-being, mental health, cognitive functioning, health behaviors, sexual and
      reproductive health, and support systems. Although most aspects of HRQoL that
      survivors discussed represented new challenges, there were several areas where
      survivors pointed out positive outcomes. There is a need for a HRQoL tool
      designed for this population of survivors, given their unique treatment and
      survivorship experience. Aspects of HRQoL related to cognition, sexual and
      reproductive health, health behaviors, and support systems are not typically
      included in generic HRQoL tools but should be assessed for this population.
      Developing HRQoL measurement instruments that capture the most significant
      aspects of HRQoL will improve the ability to track HRQoL in AYA CNS tumor
      survivors and in the long-term management of common sequelae from CNS tumors and
      their treatments. 

PMID- 25616372
TI  - Establishing Feasibility of Early Palliative Care Consultation in Pediatric
      Hematopoietic Stem Cell Transplantation.
AB  - Children and adolescents undergoing hematopoietic stem cell transplantation
      (HSCT) encounter a number of distressing physical symptoms and existential
      distress but may not be afforded timely access to palliative care services to
      help ameliorate the distress. This feasibility study investigated the
      acceptability and outcomes of early palliative care consultation to promote
      comfort in this population. A longitudinal, descriptive cohort design examined
      both provider willingness to refer and willingness of families to receive
      palliative care interventions as well as satisfaction. Feasibility was
      demonstrated by 100% referral of eligible patients and 100% of patient and family
      recruitment (N = 12). Each family received 1 to 3 visits per week (ranging from
      15 to 120 minutes) from the palliative care team. Interventions included
      supportive care counseling and integrative therapies. Families and providers
      reported high satisfaction with the nurse-led palliative care consultation.
      Outcomes included improvement or no significant change in comfort across the
      trajectory of HSCT, from the child and parental perspective. Early integration of
      palliative care in HSCT is feasible and acceptable to families and clinicians. 

PMID- 25616373
TI  - Is vascular fragility a significant concern in Ehlers-Danlos syndrome type VIA?

PMID- 25616374
TI  - Effects of excitation area of longitudinal transducer on the flexural vibration
      characteristics of a rectangular plate in stripe mode.
AB  - The flexural vibration characteristics of a rectangular plate in stripe mode,
      driven at its center by a different longitudinal vibration ultrasonic transducer
      (LVUT) with different excitation area are investigated. The variation in the
      nodal lines and corresponding resonant frequency of the rectangular plate under
      different excitation area are calculated by using finite element method (FEM).
      The results show that the resonant frequency increases with the excitation area
      of the LVUT increasing, and the nodal lines bend obviously when the radius r of
      excitation area is greater than a certain value. The experimental tests are
      carried out by the aid of Polytec PSV-400 Scanning laser Vibrometer, and the
      results agree well those of numerically calculated. It indicates that the larger
      excitation area of longitudinal transducer may affect the ultrasonic field
      radiated by the rectangular plate. 

PMID- 25616375
TI  - Ancestral state reconstruction, rate heterogeneity, and the evolution of reptile
      viviparity.
AB  - Virtually all models for reconstructing ancestral states for discrete characters
      make the crucial assumption that the trait of interest evolves at a uniform rate
      across the entire tree. However, this assumption is unlikely to hold in many
      situations, particularly as ancestral state reconstructions are being performed
      on increasingly large phylogenies. Here, we show how failure to account for such
      variable evolutionary rates can cause highly anomalous (and likely incorrect)
      results, while three methods that accommodate rate variability yield the
      opposite, more plausible, and more robust reconstructions. The random local clock
      method, implemented in BEAST, estimates the position and magnitude of rate
      changes on the tree; split BiSSE estimates separate rate parameters for pre
      specified clades; and the hidden rates model partitions each character state into
      a number of rate categories. Simulations show the inadequacy of traditional
      models when characters evolve with both asymmetry (different rates of change
      between states within a character) and heterotachy (different rates of character
      evolution across different clades). The importance of accounting for rate
      heterogeneity in ancestral state reconstruction is highlighted empirically with a
      new analysis of the evolution of viviparity in squamate reptiles, which reveal a
      predominance of forward (oviparous-viviparous) transitions and very few
      reversals. 

PMID- 25616376
TI  - Reply to "Studies on influenza virus transmission between ferrets: the public
      health risks revisited".

PMID- 25616377
TI  - Studies on influenza virus transmission between ferrets: the public health risks
      revisited.

PMID- 25616378
TI  - Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione
      and 2'-deoxycytidine.
AB  - Benzo[a]pyrene-7,8-dione (BPQ) is formed by the activation of
      benzo[a]pyrene(B[a]P), which is an environmental toxic substance that is easily
      exposed in daily life, due to P450/epoxide hydrolase, and is a substance that
      induces DNA deformation by forming adducts with DNA. In this study, to
      investigate the form of bonding between BPQ and DNA, the structures of adducts
      between BPQ and 2'-deoxycytidine were examined. To examine BPQ-dC adduct
      conformation, geometry optimization of a total of 16 structural isomers was
      performed using the density functional theory method. In the structures of BPQ-dC
      adducts, for the cis-form, the angle between BPQ and dC is nearly perpendicular;
      but for the trans-form, the bending angle is small. The trans-form had a larger
      energy gap between ground state and excited state than the cis-form, and had a
      smaller HOMO-LUMO gap than the cis-form. Therefore, it was found that the trans
      form absorbs stronger light and has higher reactivity than the cis-form.
      Molecular electrostatic potential was calculated and analyzed. The calculated ESP
      contour map shows the electrophilic and nucleophilic regions of the molecule. 

PMID- 25616379
TI  - Aberration of mitosis by hexavalent chromium in some Fabaceae members is mediated
      by species-specific microtubule disruption.
AB  - Because the detrimental effects of chromium (Cr) to higher plants have been
      poorly investigated, the present study was undertaken to verify the toxic
      attributes of hexavalent chromium [Cr(VI)] to plant mitotic microtubules (MTs),
      to determine any differential disruption of MTs during mitosis of taxonomically
      related species and to clarify the relationship between the visualized
      chromosomal aberrations and the Cr(VI)-induced MT disturbance. For this purpose,
      5-day-old uniform seedlings of Vicia faba, Pisum sativum, Vigna sinensis and
      Vigna angularis, all belonging to the Fabaceae family, were exposed to 250 MUM
      Cr(VI) supplied as potassium dichromate (K2Cr2O7) for 24, 72 and 120 h and others
      in distilled water serving as controls. Root tip samples were processed for
      tubulin immunolabelling (for MT visualization) and DNA fluorescent staining (for
      chromosomal visualization). Microscopic preparations of cell squashes were then
      examined and photographed by confocal laser scanning microscopy (CLSM). Cr(VI)
      halted seedling growth turning roots brown and necrotic. Severe chromosomal
      abnormalities and differential disturbance of the corresponding MT arrays were
      found in all mitotic phases. In particular, in V. faba MTs were primarily
      depolymerized and replaced by atypical tubulin conformations, whereas in P.
      sativum, V. sinensis and V. angularis they became bundled in a time-dependent
      manner. In P. sativum, the effects were milder compared to those of the other
      species, but in all cases MT disturbance adversely affected the proper
      aggregation of chromosomes on the metaphase plate, their segregation at anaphase
      and organization of the new nuclei at telophase. Cr(VI) is very toxic to seedling
      growth. The particular effect depends on the exact stage the cell is found at the
      time of Cr(VI) entrance and is species-specific. Mitotic MT arrays are
      differentially deranged by Cr(VI) in the different species examined, even if they
      are taxonomically related, while their disturbance underlies chromosomal
      abnormalities. Results furthermore support the view that MTs may constitute a
      reliable, sensitive and universal subcellular marker for monitoring heavy metal
      toxicity.

PMID- 25616380
TI  - Levels, potential sources and human health risk of polycyclic aromatic
      hydrocarbons (PAHs) in particulate matter (PM(10)) in Kumasi, Ghana.
AB  - Airborne particulate samples were collected on quartz filters to determine the
      concentrations, sources and health risks of polycyclic aromatic hydrocarbons
      (PAHs) in air in Kumasi, Ghana. A total of 32 air samples were collected in Kwame
      Nkrumah University of Science and Technology (KNUST) campus (pristine site) and
      city centre (CC). Samples were extracted with 1:2 v/v acetone/hexane mixture
      prior to GC-MS analyses. The sum of concentrations of 17 PAHs in air ranged from
      0.51 to 16 (KNUST) and 19-38 ng/m(3) (CC). The concentration of benzo[a]pyrene,
      BaP, ranged from below detection limit to 0.08 ng/m(3) (KNUST) and 1.6 to 5.6
      ng/m(3) (CC). Chemical mass balance model showed that PAHs in air in Kumasi were
      mainly from fuel combustion. The total BaP equivalent concentration (BaPeq) in CC
      was 18 times higher compared to KNUST; based on the European Legislation and
      Swedish and UK Standards for BaP in air, CC could be classified as highly
      polluted. Estimated carcinogenicity of PAHs in terms of BaPeq indicated that BaP
      was the principal PAH contributor in CC (70%). Health risk to adults and children
      associated with PAH inhalation was assessed by taking into account the lifetime
      average daily dose and corresponding incremental lifetime cancer risk (ILCR). The
      ILCR was within the acceptable range (10(-6) to 10(-4)), indicating low health
      risk to residents.

PMID- 25616381
TI  - Transport of short-chain perfluoroalkyl acids from concentrated fluoropolymer
      facilities to the Daling River estuary, China.
AB  - After global commercialization of short-chain perfluoroalkyl acids (PFAAs) as
      substitutes to conventional long-chain PFAAs by the major manufacturers, two
      fluorine industry parks for production of short-chain PFAAs located in the Daling
      River Basin of northern China have developed rapidly in the last few years. This
      study provides a systematic assessment of sources, emissions, transportation, and
      potential risks of the PFAAs in this area. The C4 perfluorobutane sulfonic acid
      (PFBS) and perfluorobutanoic acid (PFBA) were the predominant short-chain PFAAs
      in river water, with maximum concentrations of 2.90 and 1.35 MUg/L, respectively.
      Park 1 equipped with a telomerization process was identified to be the source of
      linear and branched mixtures of PFBS, PFBA, and perfluorooctanoic acid (PFOA),
      while park 2 with an electrochemical fluorination process (ECF) was identified to
      be the source of linear and branched mixtures of PFBS and PFOA. Partition
      coefficients between water and sediment were consistent for C4-C8 perfluoroalkyl
      carboxylic acids (PFCAs) but directly proportional to C9-C11 PFCAs and
      perfluoroalkyl sulfonic acids (PFSAs). Analysis on the health risk of PFBS and
      PFBA suggested that they were not without risk since short chain PFAAs are known
      to be recalcitrant during water treatment. 

PMID- 25616382
TI  - Phytotoxicity assessment of atrazine on growth and physiology of three emergent
      plants.
AB  - The emergent plants Acorus calamus, Lythrum salicaria, and Scirpus
      tabernaemontani were exposed to atrazine for 15, 30, 45, and 60 days in a
      hydroponic system. Effects were evaluated investigating plant growth, chlorophyll
      (Chl) content, peroxidase (POD) activity, and malondialdehyde (MDA) content.
      Results showed that selected plants survived in culture solution with atrazine
      <=8 mg L(-1), but relative growth rates decreased significantly in the first 15
      day exposure. Chla content decreased, but MDA increased with increasing atrazine
      concentration. S. tabernaemontani was the most insensitive species, followed by
      A. calamus and L.salicaria. The growth indicators exhibited significant changes
      in the early stage of atrazine exposure; subsequently, the negative impacts
      weakened and disappeared. Plant growth may be more representative of emergent
      plant fitness than physiological endpoints in toxicity assessment of herbicides
      to emergent plants. 

PMID- 25616384
TI  - Detoxification of the veterinary antibiotic chloramphenicol using electron beam
      irradiation.
AB  - Electron beam irradiation has shown potential as an alternative process for the
      treatment of industrial effluents that contain toxic organic chemicals. This
      study investigated the effectiveness of electron beam in degrading
      chloramphenicol (CAP) in aqueous solution. The degradation efficiency was 32.4%
      at 1 kGy, 86.9% at 5 kGy, and 100% at 10 kGy. The total organic carbon (TOC) of
      CAP in aqueous solution declined 4.6% at 1 kGy, 12.1% at 5 kGy, and 17.1% at 10
      kGy of irradiation with electron beam. The CAP degradation products after
      irradiation were CAP1 ([M + H] m/z 307.1), CAP2 ([M + H] m/z 291.1), and CAP3 ([M
      + H] m/z 321.1). The degradation products were tested for microbial toxicity
      against Escherichia coli, Pseudomonas putida, and Bacillus subtilis and did not
      show any toxic antimicrobial effects caused by the CAP degradation products after
      irradiation with electron beam. The results of this study suggest that electron
      beam irradiation is the best technology for the comprehensive treatment of
      veterinary antibiotics at wastewater treatment plants.

PMID- 25616383
TI  - Impact of clay mineral, wood sawdust or root organic matter on the bacterial and
      fungal community structures in two aged PAH-contaminated soils.
AB  - The high organic pollutant concentration of aged polycyclic aromatic hydrocarbon
      (PAH)-contaminated wasteland soils is highly recalcitrant to biodegradation due
      to its very low bioavailability. In such soils, the microbial community is well
      adapted to the pollution, but the microbial activity is limited by nutrient
      availability. Management strategies could be applied to modify the soil microbial
      functioning as well as the PAH contamination through various amendment types. The
      impact of amendment with clay minerals (montmorillonite), wood sawdust and
      organic matter plant roots on microbial community structure was investigated on
      two aged PAH-contaminated soils both in laboratory and 1-year on-site pot
      experiments. Total PAH content (sum of 16 PAHs of the US-EPA list) and polar
      polycyclic aromatic compounds (pPAC) were monitored as well as the available PAH
      fraction using the Tenax method. The bacterial and fungal community structures
      were monitored using fingerprinting thermal gradient gel electrophoresis (TTGE)
      method. The abundance of bacteria (16S rRNA genes), fungi (18S rRNA genes) and
      PAH degraders (PAH-ring hydroxylating dioxygenase and catechol dioxygenase genes)
      was followed through qPCR assays. Although the treatments did not modify the
      total and available PAH content, the microbial community density, structure and
      the PAH degradation potential changed when fresh organic matter was provided as
      sawdust and under rhizosphere influence, while the clay mineral only increased
      the percentage of catechol-1,2-dioxygenase genes. The abundance of bacteria and
      fungi and the percentage of fungi relative to bacteria were enhanced in soil
      samples supplemented with wood sawdust and in the plant rhizospheric soils. Two
      distinct fungal populations developed in the two soils supplemented with sawdust,
      i.e. fungi related to Chaetomium and Neurospora genera and Brachyconidiellopsis
      and Pseudallescheria genera, in H and NM soils respectively. Wood sawdust
      amendment favoured the development of PAH-degrading bacteria holding Gram
      negative PAH-ring hydroxylating dioxygenase, catechol-1,2-dioxygenase and
      catechol-2,3-dioxygenase genes. Regarding the total community structure, bacteria
      closely related to Thiobacillus (beta-Proteobacteria) and Steroidobacter (gamma
      Proteobacteria) genera were favoured by wood sawdust amendment. In both soils,
      plant rhizospheres induced the development of fungi belonging to Ascomycota and
      related to Alternaria and Fusarium genera. Bacteria closely related to
      Luteolibacter (Verrucomicrobia) and Microbacterium (Actinobacteria) were favoured
      in alfalfa and ryegrass rhizosphere. 

PMID- 25616385
TI  - Role of solvent properties of aqueous media in macromolecular crowding effects.
AB  - Analysis of the macromolecular crowding effects in polymer solutions show that
      the excluded volume effect is not the only factor affecting the behavior of
      biomolecules in a crowded environment. The observed inconsistencies are commonly
      explained by the so-called soft interactions, such as electrostatic, hydrophobic,
      and van der Waals interactions, between the crowding agent and the protein, in
      addition to the hard nonspecific steric interactions. We suggest that the changes
      in the solvent properties of aqueous media induced by the crowding agents may be
      the root of these "soft" interactions. To check this hypothesis, the
      solvatochromic comparison method was used to determine the solvent
      dipolarity/polarizability, hydrogen-bond donor acidity, and hydrogen-bond
      acceptor basicity of aqueous solutions of different polymers (dextran,
      poly(ethylene glycol), Ficoll, Ucon, and polyvinylpyrrolidone) with the polymer
      concentration up to 40% typically used as crowding agents. Polymer-induced
      changes in these features were found to be polymer type and concentration
      specific, and, in case of polyethylene glycol (PEG), molecular mass specific.
      Similarly sized polymers PEG and Ucon producing different changes in the solvent
      properties of water in their solutions induced morphologically different alpha
      synuclein aggregates. It is shown that the crowding effects of some polymers on
      protein refolding and stability reported in the literature can be quantitatively
      described in terms of the established solvent features of the media in these
      polymers solutions. These results indicate that the crowding agents do induce
      changes in solvent properties of aqueous media in crowded environment. Therefore,
      these changes should be taken into account for crowding effect analysis. 

PMID- 25616386
TI  - Isolation of a novel lodging resistance QTL gene involved in strigolactone
      signaling and its pyramiding with a QTL gene involved in another mechanism.
AB  - Lodging has been a major roadblock to attaining increased crop productivity. In
      an attempt to understand the mechanism for culm strength in rice, we isolated an
      effective quantitative trait locus (QTL), STRONG CULM3 (SCM3), the causal gene of
      which is identical to rice TEOSINTE BRANCHED1 (OsTB1), a gene previously reported
      to positively control strigolactone (SL) signaling. A near-isogenic line (NIL)
      carrying SCM3 showed enhanced culm strength and increased spikelet number despite
      the expected decrease in tiller number, indicating that SL also has a positive
      role in enhancing culm strength and spikelet number. We produced a pyramiding
      line carrying SCM3 and SCM2, another QTL encoding APO1 involved in panicle
      development. The NIL-SCM2+SCM3 showed a much stronger culm than NIL-SCM2 and NIL
      SCM3 and an increased spikelet number caused by the additive effect of these
      QTLs. We discuss the importance of utilizing suitable alleles of these STRONG
      CULM QTLs without inducing detrimental traits for breeding. 

PMID- 25616387
TI  - Arabidopsis AT-hook protein TEK positively regulates the expression of
      arabinogalactan proteins for Nexine formation.
AB  - Nexine is a conserved layer of the pollen wall. We previously reported that the
      nexine layer is absent in the knockout mutant of Arabidopsis TRANSPOSABLE ELEMENT
      SILENCING VIA AT-HOOK (TEK) gene. In this study, we investigated the molecular
      regulatory functions of TEK in pollen development and identified the genes
      encoding Arabinogalactan proteins (AGPs) as direct targets of TEK, which are
      essential for nexine formation. Phenotypic similarity between tek and the TEK
      SRDX transgenic lines suggest that TEK plays a role in transcriptional activation
      in anther development. Microarray analysis identified a total of 661 genes
      downregulated in tek, including four genes encoding AGPs, AGP6, AGP11, AGP23, and
      AGP40. Electrophoretic mobility shift assays showed that TEK could directly bind
      the nuclear matrix attachment region (MAR) and the promoter of AGP6. Chromatin
      immunoprecipitation followed by PCR analysis demonstrated that TEK is enriched in
      the promoters of the four AGP genes. Expression of AGP6 driven by the TEK
      promoter in tek partially rescued both nexine formation and plant fertility.
      These results indicate that TEK directly regulates AGP expression in the anther
      to control nexine layer formation. We also proposed that glycoproteins might be
      essential components of the nexine layer in the pollen wall. 

PMID- 25616388
TI  - XA23 is an executor R protein and confers broad-spectrum disease resistance in
      rice.
AB  - The majority of plant disease resistance (R) genes encode proteins that share
      common structural features. However, the transcription activator-like effector
      (TALE)-associated executor type R genes show no considerable sequence homology to
      any known R genes. We adopted a map-based cloning approach and TALE-based
      technology to isolate and characterize Xa23, a new executor R gene derived from
      wild rice (Oryza rufipogon) that confers an extremely broad spectrum of
      resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo).
      Xa23 encodes a 113 amino acid protein that shares 50% identity with the known
      executor R protein XA10. The predicted transmembrane helices in XA23 also overlap
      with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically
      activated by AvrXa23, a TALE present in all examined Xoo field isolates.
      Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23
      but differs in promoter region by lacking the TALE binding element (EBE) for
      AvrXa23. XA23 can trigger a strong hypersensitive response in rice, tobacco, and
      tomato. Our results provide the first evidence that plant genomes have an
      executor R gene family of which members execute their function and spectrum of
      disease resistance by recognizing the cognate TALEs in the pathogen. 

PMID- 25616389
TI  - Bidirectional interactions between the baroreceptor reflex and arousal: an
      update.
AB  - Studies involving genetic engineering on animal models and mathematical analysis
      of cardiovascular signals on humans are shedding new light on the interactions
      between the arterial baroreceptor reflex (baroreflex) and arousal. Baroreceptor
      stimulation, if very mild or performed under anaesthesia, may inhibit cortical
      arousal. However, substantial increases or decreases in baroreflex activation
      cause arousal in animal models and human subjects in physiological conditions. On
      the other hand, cardiovascular changes during autonomic arousals and between the
      states of wakefulness and sleep involve changes in the baroreflex set point and
      balance with central autonomic commands. Neural connectivity and functional data
      suggest that the nucleus of the solitary tract, adrenergic C1 neurons of the
      medulla, and the parabrachial nucleus of the pons mediate the bidirectional
      interactions between the baroreflex and arousal. These interactions may
      constitute a positive feedback loop that facilitates sharp and coordinated brain
      state and autonomic transitions upon arousal: upon arousal, central autonomic
      commands may increase blood pressure, thereby loading baroreceptors and further
      increasing arousal. Anomalies of this feedback loop may play a role in the
      pathophysiology of disease conditions associated with cardiovascular and sleep
      wake cycle alterations. These conditions include: obstructive sleep apnoea
      syndrome, with its association with excessive daytime sleepiness and baroreflex
      impairment; and insomnia, with its association with autonomic hyperarousal and
      hypertension. When faced with disorders associated with cardiovascular and sleep
      wake cycle alterations, clinical reasoning should entertain the possibility that
      both conditions are strongly influenced by anomalies of baroreflex function. 

PMID- 25616390
TI  - Perceived neighborhood safety and sleep quality: a global analysis of six
      countries.
AB  - OBJECTIVE: Building on previous North American and European studies of
      neighborhood context and sleep quality, we tested whether several self-reported
      sleep outcomes (sleep duration, insomnia symptoms, sleepiness, lethargy, and
      overall sleep quality) vary according to the level of perceived neighborhood
      safety in six countries: Mexico, Ghana, South Africa, India, China, and Russia.
      METHODS: Using data (n = 39,590) from Wave I of the World Health Organization's
      Longitudinal Study on Global Ageing and Adult Health (2007-2010), we estimated a
      series of multinomial and binary logistic regression equations to model each
      sleep outcome within each country. RESULTS: Taken together, our results show that
      respondents who feel safe from crime and violence in their neighborhoods tend to
      exhibit more favorable sleep outcomes than respondents who feel less safe. This
      general pattern is especially pronounced in China and Russia, moderately evident
      in Mexico, Ghana, and South Africa, and sporadic in India. Perceptions of
      neighborhood safety are strongly associated with insomnia symptoms and poor sleep
      quality (past 30 days), moderately associated with sleepiness, lethargy, and poor
      sleep quality (past 2 days), and inconsistently associated with sleep duration
      (past two days). CONCLUSIONS: We show that perceived neighborhood safety is
      associated with more favorable self-reported sleep outcomes in six understudied
      countries. Additional research is needed to replicate our findings using
      longitudinal data, more reliable neighborhood measures, and more direct measures
      of sleep quality in these and other regions of the world.

PMID- 25616392
TI  - Clinical results with two different pharmaceutical preparations of riboflavin in
      corneal cross-linking: an 18-month follow up.
AB  - BACKGROUND: Comparison of long-term clinical results of two different
      pharmaceutical formulations used in corneal cross-linking (CXL) in keratoconus
      patients. METHODS: Sixty eyes of 60 keratoconus patients underwent CXL in two
      groups. We used riboflavin preparations from Sina Darou, Iran in group A, and
      Streuli Pharma, Switzerland in group B. Here we made inter-group comparison of
      changes in vision, refraction, Pentacam indices, corneal biomechanical indices,
      and endothelial cell count (ECC) 18 months after CXL. RESULTS: Since four
      patients were lost to follow-up, 56 eyes (28 eyes in each group) were compared.
      Mean improvement in uncorrected visual acuity (UCVA) was 0.31 +/- 0.65 LogMAR
      (P=0.014) in group A and 0.24 +/- 0.62 LogMAR (P=0.082) in group B. Best
      corrected visual acuity (BCVA) remained quite unchanged in both groups (P=0.774).
      Mean spherical refractive error reduced by 0.45 +/- 1.15 diopter (D) (P=0.041) in
      group A and 0.27 +/- 1.73 D (P=0.458) in group B (P=0.655). Cylinder error and
      spherical equivalent had a similar trend without any change. Max-K (P=0.006) and
      mean-K (P=0.044) decreased significantly more in group A compared to group B. The
      reduction in CCT was significantly more in group A than group B (P=0.004). Q
      value was quite unchanged in both groups (P=0.704). The inter-group difference in
      CH reduction was borderline significant statistically (P=0.057). Changes in
      corneal resistance factor and endothelial cell count were not significantly
      different between two groups (P=0.117 and P=0.229). CONCLUSION: Clinical results
      of CXL with the domestic preparation of riboflavin are similar to that achieved
      with the Swiss made product in some aspects, and it is the preferred brand in
      some other aspects. This study will continue to report longer follow-up results.
      TRIAL REGISTRATION: IRCT201212034333N2.

PMID- 25616393
TI  - The authors respond.

PMID- 25616391
TI  - Pentraxin 3 mediates neurogenesis and angiogenesis after cerebral ischaemia.
AB  - BACKGROUND: The acute phase protein pentraxin 3 (PTX3) is a new biomarker of
      stroke severity and is a key regulator of oedema resolution and glial responses
      after cerebral ischaemia, emerging as a possible target for brain repair after
      stroke. Neurogenesis and angiogenesis are essential events in post-stroke
      recovery. Here, we investigated for the first time the role of PTX3 in
      neurogenesis and angiogenesis after stroke. METHODS: PTX3 knockout (KO) or wild
      type (WT) mice were subjected to experimental cerebral ischaemia (induced by
      middle cerebral artery occlusion (MCAo)). Poststroke neurogenesis was assessed by
      nestin, doublecortin (DCX) and bromodeoxyuridine (BrdU) immunostaining, whereas
      angiogenesis was assessed by BrdU, vascular endothelial growth factor receptor 2
      (VEGFR2) and PECAM-1 immunostaining. In vitro neurogenesis and angiogenesis
      assays were carried out on neurospheres derived from WT or interleukin-1beta (IL
      1beta) KO mice, and mouse endothelial cell line bEnd.5 respectively. Behavioural
      function was assessed in WT and PTX3 KO mice using open-field, motor and Y-maze
      tests. RESULTS: Neurogenesis was significantly reduced in the dentate gyrus (DG)
      of the hippocampus of PTX3 KO mice, compared to WT mice, 6 days after MCAo. In
      addition, recombinant PTX3 was neurogenic in vitro when added to neurospheres,
      which was mediated by IL-1beta. In vivo poststroke angiogenesis was significantly
      reduced in PTX3 KO mice compared to WT mice 14 days after MCAo, as revealed by
      reduced vascular density, less newly formed blood vessels and decreased
      expression of VEGFR2. In vitro, recombinant PTX3 induced marked endothelial
      cellular proliferation and promoted formation of tube-like structures of
      endothelial cell line bEnd.5. Finally, a lack of PTX3 potentiated motor deficits
      14 days after MCAo. CONCLUSIONS: These results indicate that PTX3 mediates
      neurogenesis and angiogenesis and contributes to functional recovery after
      stroke, highlighting a key role of PTX3 as a mediator of brain repair and
      suggesting that PTX3 could be used as a new target for stroke therapy.

PMID- 25616394
TI  - Improvements in long-term survival after spinal cord injury?
AB  - OBJECTIVE: To investigate whether there have been improvements in long-term
      survival after spinal cord injury in recent decades. DESIGN: Survival analysis
      using time-varying covariates. The outcome variable was survival or mortality,
      and the explanatory variables were age, sex, level and grade of injury, and
      calendar year. The data were analyzed using the logistic regression model,
      Poisson regression model with comparison to the general population, and the
      computation of standardized mortality ratios for various groups. SETTING:
      National Spinal Cord Injury Model Systems facilities. PARTICIPANTS: Persons
      (N=31,531) who survived 2 years postinjury, were older than 10 years, and who did
      not require ventilator support. These persons contributed 484,979 person-years of
      data, with 8536 deaths over the 1973 to 2012 study period. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Survival; survival relative to the general
      population; life expectancy. RESULTS: After adjustment for age, sex, race,
      etiology of injury, time since injury, and level and grade of injury, mortality
      in persons with spinal cord injury was higher in the 2005 to 2012 period than in
      1990 to 2004 or 1980 to 1989, the odds ratios for these 3 periods were .857,
      .826, and .802 as compared with the 1970 to 1979 reference period. CONCLUSIONS:
      There was no evidence of improvement. Long-term survival has not changed over the
      past 30 years.

PMID- 25616395
TI  - Predicting the response to botulinum toxin treatment in children with cerebral
      palsy.

PMID- 25616396
TI  - Nasal CPAP or INSURE for RDS.

PMID- 25616397
TI  - Predictors of Preoperative Weight Loss in Morbidly Obese Adults Waiting for
      Bariatric Surgery: A Prospective Cohort Study.
AB  - BACKGROUND: Preoperative weight loss is encouraged before bariatric surgery, as
      it is associated with improved surgical conditions. It has also been related to
      better postoperative outcomes, but this relationship is less clear. However,
      little is known about what predicts weight loss preoperatively, so the aim was to
      identify psychosocial and clinical predictors of preoperative weight loss.
      METHODS: Weight was measured at the first visit, the time of surgery approval,
      and on the day of surgery in 286 bariatric surgery patients (227 women). A
      questionnaire consisting of multiple psychosocial measures was completed before
      surgery. RESULTS: Preoperatively, patients experienced a mean weight loss of 3.8
      %. Men lost significantly more weight than women (mean = 5.4, SD = 6.0 vs. mean =
      3.4, SD = 5.8, t = -2.3, p < 0.05), and 43.2 % of the patients lost >= 5% of
      their body weight. A high weight loss goal (beta = 0.20, p < 0.001), frequent
      self-weighing (beta = 0.18, p < 0.002), and being close to or at highest lifetime
      weight when applying for surgery (beta = -0.30, p < 0.0001) were identified as
      predictors of weight loss, after controlling for body mass index (BMI), gender,
      and length of preoperative time period. CONCLUSIONS: A relatively low proportion
      of patients lost the recommended weight preoperatively. Our results indicate that
      patients benefit from monitoring weight preoperatively and that allowing patients
      to keep their high weight loss goals may contribute to higher weight loss.
      Further investigation of these predictors could provide valuable knowledge
      regarding how to support and motivate patients to lose weight preoperatively.

PMID- 25616399
TI  - NHS needs another L65bn by 2030-31, think tank says.

PMID- 25616398
TI  - Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes
      Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal
      Circulation.
AB  - BACKGROUND: Preterm prelabor rupture of the fetal membranes (PPROM) is a
      significant contributor to the morbidity and mortality of preterm birth,
      particularly in the setting of chorioamnionitis. No sensitive or specific
      diagnostic or predictive test currently exists for the accurate diagnosis of
      chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in
      the maternal blood and examine whether they were increased in association with
      chorioamnionitis at delivery. METHODS/RESULTS: We performed a prospective cohort
      study of women recruited with PPROM at a mean gestational age of 28.9 weeks at
      risk of developing chorioamnionitis. Blood was sampled from participants, and the
      expression of mRNA coding for proinflammatory genes was measured in women with
      and without chorioamnionitis at the time of delivery as well as gestation-matched
      healthy controls. Expression was measured using quantitative polymerase chain
      reaction (PCR) and also digital PCR. Interleukin 1beta (IL1B) mRNA expression in
      maternal blood was elevated in women with chorioamnionitis compared to gestation
      matched controls. Importantly, among women admitted with PPROM, digital PCR
      confirmed a significant increase in IL1B expression in maternal blood in women
      with chorioamnionitis compared to women without chorioamnionitis. Polymerase
      chain reaction array revealed that CD14, nuclear factor of kappa light
      polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor
      receptor super family-interacting serine-threonine kinase 1 mRNA were
      significantly increased in women with chorioamnionitis compared to controls.
      Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients
      with chorioamnionitis compared to controls and that CD14 levels increased over
      time in patients with PPROM having chorioamnionitis. CONCLUSION: Measuring
      circulating proinflammatory mRNA in women with PPROM may distinguish those with
      chorioamnionitis from those without, in turn providing better targeted therapies
      and appropriate timing of delivery.

PMID- 25616400
TI  - PM10 mass concentration and oxidative capacity of moxa smoke.
AB  - BACKGROUND: The burning of moxa floss in moxibustion releases moxa smoke
      containing a substantial amount of particulate matter (PM10) into the
      environment, which has generated safety concerns about its potential health
      impact. DESIGN: Plasmid scission assay was performed using PM10 collected from
      moxibustion clinics. METHODS: PM10 was collected in winter 2012 by burning three
      types of moxa floss samples in moxibustion simulation clinics, and the resulting
      PM10 mass concentration was calculated. Oxidative capacity of the PM10 samples
      was measured by plasmid scission assay and the percentage of DNA damage at dosage
      500 ug ml(-1) (D500) was calculated by linear regression analysis. RESULTS: The
      average PM10 mass concentration of samples A (3 years and 3:1 ratio), B (3 years
      and 8:1 ratio) and C (10 years and 3:1 ratio) was 273.33, 172.22 and 168.89
      MUg/m(3), respectively. The D500 oxidative capacity of PM10 was on average
      24.25%, 27.83% and 28.07% for samples A, B and C, respectively. No significant
      difference was found in the PM10-induced oxidative damage by moxa smoke produced
      from the three types of moxa floss. CONCLUSIONS: PM10 mass concentrations from
      the three types of moxa floss combustion exceeded internationally recommended
      levels. Despite so, PM10 mass concentration of moxa smoke was much lower than
      biomass and coal combustion and similar to that of gas combustion. The oxidative
      DNA damage induced by individual PM10 in moxibustion environment was lower than
      that reported in other environments, indicating that moxibustion-derived PM10
      might not be as injurious to human health as generally assumed.

PMID- 25616401
TI  - The Effect of Response Format on the Psychometric Properties of the Narcissistic
      Personality Inventory: Consequences for Item Meaning and Factor Structure.
AB  - The Narcissistic Personality Inventory (NPI) is currently the most widely used
      measure of narcissism in social/personality psychology. It is also relatively
      unique because it uses a forced-choice response format. We investigate the
      consequences of changing the NPI's response format for item meaning and factor
      structure. Participants were randomly assigned to one of three conditions: 40
      forced-choice items (n = 2,754), 80 single-stimulus dichotomous items (i.e.,
      separate true/false responses for each item; n = 2,275), or 80 single-stimulus
      rating scale items (i.e., 5-point Likert-type response scales for each item; n =
      2,156). Analyses suggested that the "narcissistic" and "nonnarcissistic" response
      options from the Entitlement and Superiority subscales refer to independent
      personality dimensions rather than high and low levels of the same attribute. In
      addition, factor analyses revealed that although the Leadership dimension was
      evident across formats, dimensions with entitlement and superiority were not as
      robust. Implications for continued use of the NPI are discussed. 

PMID- 25616402
TI  - Reduced blood pressure and cholesterol are main factors in fall in deaths from
      coronary heart disease.

PMID- 25616403
TI  - A new physiologically based pharmacokinetic model for the prediction of
      gastrointestinal drug absorption: translocation model.
AB  - This study aimed to construct a new local pharmacokinetic model of
      gastrointestinal absorption, the translocation model (TLM), using an anatomically
      relevant, minimally segmented structure to explain linear and nonlinear
      intestinal absorption, metabolism, and transport. The TLM was based on the
      concept of a single absorption site that flexibly moves, expands, and shrinks
      along with the length of the gastrointestinal tract after the intake of an oral
      dose. The structure of the small intestine is continuous, and various time- and
      location-dependent issues are freely incorporated in the analysis. Since the
      model has only one absorption site, understanding and modification of factors
      affecting absorption are simple. The absorption site is composed of four
      compartments: solid drug in the lumen, solution drug in the lumen, concentration
      in the enterocytes, and concentration in the lamina propria. The lamina propria
      includes the blood capillaries. Blood flow in the absorption site of the lamina
      propria appropriately accounts for the absorption. In the TLM, the permeability
      of the apical membrane and that of the basolateral membrane are distinct. By
      considering plicate, villi, and microvilli expansions of the surface area, the
      apparent permeability measured in Caco-2 experiments was converted to the
      effective permeability in vivo. The intestinal availability, bioavailability, and
      dose product of intestinal availability and absorption rate relationship of the
      model drugs were well explained using the TLM. The TLM would be a useful tool for
      the consideration of local pharmacokinetics in the gastrointestinal tract in
      various situations. 

PMID- 25616405
TI  - Trichomonas vaginalis infection induces vaginal CD4+ T-cell infiltration in a
      mouse model: a vaccine strategy to reduce vaginal infection and HIV transmission.
AB  - BACKGROUND: Complications related to the diagnosis and treatment of Trichomonas
      vaginalis infection, as well as the association between T. vaginalis infection
      and increased transmission of and susceptibility to human immunodeficiency virus,
      highlight the need for alternative interventions. We tested a human-safe,
      aluminum hydroxide-adjuvanted whole-cell T. vaginalis vaccine for efficacy in a
      BALB/c mouse model of vaginal infection. METHODS: A whole-cell T. vaginalis
      vaccine was administered subcutaneously to BALB/c mice, using a prime-boost
      vaccination schedule. CD4(+) T-cell infiltration in the murine vaginal tissue and
      local and systemic levels of immunoglobulins were measured at time points up to 4
      weeks following infection. RESULTS: Vaccination reduced the incidence and
      increased the clearance of T. vaginalis infection and induced both systemic and
      local humoral immune responses. CD4(+) T cells were detected in vaginal tissues
      following intravaginal infection with T. vaginalis but were not seen in
      uninfected mice. The presence of CD4(+) T cells following T. vaginalis infection
      can potentially increase susceptibility to and transmission of human
      immunodeficiency virus. CONCLUSIONS: The vaccine induces local and systemic
      immune responses and confers significantly greater protection against vaginal
      infection than seen in unvaccinated mice (P < .005). These data support the
      potential for a human vaccine against T. vaginalis infection that could also
      influence the incidence of human immunodeficiency virus infection.

PMID- 25616404
TI  - Immunosuppressive Tryptophan Catabolism and Gut Mucosal Dysfunction Following
      Early HIV Infection.
AB  - BACKGROUND: Tryptophan (Trp) catabolism into kynurenine (Kyn) contributes to
      immune dysfunction in chronic human immunodeficiency virus (HIV) infection. To
      better define the relationship between Trp catabolism, inflammation, gut mucosal
      dysfunction, and the role of early antiretroviral therapy (ART), we prospectively
      assessed patients early after they acquired HIV. METHODS: Forty patients in the
      early phase of infection were longitudinally followed for 12 months after
      receiving a diagnosis of HIV infection; 24 were untreated, and 16 were receiving
      ART. Kyn/Trp ratio, regulatory T-cells (Tregs) frequency, T-cell activation,
      dendritic cell counts, and plasma levels of gut mucosal dysfunction markers
      intestinal-type fatty acid-binding protein, soluble suppression of tumorigenicity
      2, and lipopolysaccharide were assessed. RESULTS: Compared with healthy subjects,
      patients in the early phase of infection presented with elevated Kyn/Trp ratios,
      which further increased in untreated patients but normalized in ART recipients.
      Accordingly, in untreated subjects, the elevated Treg frequency observed at
      baseline continued to increase over time. The highest CD8(+) T-cell activation
      was observed during the early phase of infection and decreased in untreated
      patients, whereas activation normalized in ART recipients. The Kyn/Trp ratio was
      positively associated with CD8(+) T-cell activation and levels of inflammatory
      cytokines (interleukin 6, interferon gamma-inducible protein 10, interleukin 18,
      and tumor necrosis factor alpha) and negatively associated with dendritic cell
      frequencies at baseline and in untreated patients. However, ART did not normalize
      plasma levels of gut mucosal dysfunction markers. CONCLUSIONS: Early initiation
      of ART normalized enhanced Trp catabolism and immune activation but did not
      improve plasma levels of gut mucosal dysfunction markers.

PMID- 25616406
TI  - 3D delayed-enhanced magnetic resonance sequences improve conducting channel
      delineation prior to ventricular tachycardia ablation.
AB  - AIMS: Non-invasive depiction of conducting channels (CCs) is gaining interest for
      its usefulness in ventricular tachycardia (VT) ablation. The best imaging
      approach has not been determined. We compared characterization of myocardial scar
      with late-gadolinium enhancement cardiac magnetic resonance using a navigator
      gated 3D sequence (3D-GRE) and conventional 2D imaging using either a single shot
      inversion recovery steady-state-free-precession (2D-SSFP) or inversion-recovery
      gradient echo (2D-GRE) sequence. METHODS AND RESULTS: We included 30 consecutive
      patients with structural heart disease referred for VT ablation. Preprocedural
      myocardial characterization was conducted in a 3 T-scanner using 2D-GRE, 2D-SSFP
      and 3D-GRE sequences, yielding a spatial resolution of 1.4 * 1.4 * 5 mm, 2 * 2 *
      5 mm, and 1.4 * 1.4 * 1.4 mm, respectively. The core and border zone (BZ) scar
      components were quantified using the 60% and 40% threshold of maximum pixel
      intensity, respectively. A 3D scar reconstruction was obtained for each sequence.
      An electrophysiologist identified potential CC and compared them with results
      obtained with the electroanatomic map (EAM). We found no significant differences
      in the scar core mass between the 2D-GRE, 2D-SSFP, and 3D-GRE sequences (mean
      7.48 +/- 6.68 vs. 8.26 +/- 5.69 and 6.26 +/- 4.37 g, respectively, P = 0.084).
      However, the BZ mass was smaller in the 2D-GRE and 2D-SSFP than in the 3D-GRE
      sequence (9.22 +/- 5.97 and 9.39 +/- 6.33 vs. 10.92 +/- 5.98 g, respectively; P =
      0.042). The matching between the CC observed in the EAM and in 3D-GRE was 79.2%;
      when comparing the EAM and the 2D-GRE and the 2D-SSFP sequence, the matching
      decreased to 61.8% and 37.7%, respectively. CONCLUSION: 3D scar reconstruction
      using images from 3D-GRE sequence improves the overall delineation of CC prior to
      VT ablation.

PMID- 25616407
TI  - The first Latin American Catheter Ablation Registry.
AB  - AIMS: To assess the results of transcatheter ablation of cardiac arrhythmias in
      Latin America and establish the first Latin American transcatheter ablation
      registry. METHODS AND RESULTS: All ablation procedures performed between 1
      January and 31 December 2012 were analysed retrospectively. Data were obtained on
      the characteristics and resources of participating centres (public or private
      institution, number of beds, cardiac surgery availability, type of room for the
      procedures, days per week assigned to electrophysiology procedures, type of
      fluoroscopy equipment, availability and type of electroanatomical mapping system,
      intracardiac echo, cryoablation, and number of electrophysiologists) and the
      results of 17 different ablation substrates: atrio-ventricular node reentrant
      tachycardia, typical atrial flutter, atypical atrial flutter, left free wall
      accessory pathway, right free wall accessory pathway, septal accessory pathway,
      right-sided focal atrial tachycardia, left-sided focal atrial tachycardia,
      paroxysmal atrial fibrillation, non-paroxysmal atrial fibrillation, atrio
      ventricular node, premature ventricular complex, idiopathic ventricular
      tachycardia, post-myocardial infarction ventricular tachycardia, ventricular
      tachycardia in chronic chagasic cardiomyopathy, ventricular tachycardia in
      congenital heart disease, and ventricular tachycardias in other structural heart
      diseases. Data of 15 099 procedures were received from 120 centres in 13
      participating countries (Argentina, Bolivia, Brazil, Chile, Colombia, Cuba, El
      Salvador, Guatemala, Mexico, Peru, Dominican Republic, Uruguay, and Venezuela).
      Accessory pathway was the group of arrhythmias most frequently ablated (31%),
      followed by atrio-ventricular node reentrant tachycardia (29%), typical atrial
      flutter (14%), and atrial fibrillation (11%). Overall success was 92% with the
      rate of global complications at 4% and mortality 0.05%. CONCLUSION: Catheter
      ablation in Latin America can be considered effective and safe.

PMID- 25616409
TI  - Fruit Polyphenols: A Review of Anti-inflammatory Effects in Humans.
AB  - Underlying etiological factors in the development of obesity-related chronic
      diseases are long-term imbalances of oxidative and inflammatory stress leading to
      tissue dysfunction, damage, and ultimately failure. Poor dietary quality
      contributes significantly to the oxidative and inflammatory status of an
      individual. Conversely, various dietary approaches, including specific dietary
      factors can mitigate or prevent the occurrence of these risk-conferring
      imbalances brought about by modern lifestyle. Plant-derived polyphenolic
      compounds are well known for their antioxidant properties. Recent evidence
      indicates these compounds may confer anti-inflammatory and/or inflammatory
      response stabilizing activities, which would have important implications in
      health maintenance and disease risk reduction. Commonly consumed fruits, such as
      grapes, berries, and oranges/orange juice, contain polyphenolic compounds that
      have been studied for their effects on inflammation, but the nature and extent of
      their effects in humans remain unclear. Therefore, this article aims to provide a
      comprehensive overview of human clinical trials investigating the acute and
      chronic (feeding) effect of polyphenols from commonly consumed fruits or their
      derived products on inflammation. 

PMID- 25616410
TI  - Characterizing Stressors and Modifiable Health Risk Factors Among Homeless
      Smokers: An Exploratory Pilot Study.
AB  - This pilot study was conducted to explore the associations between stressors
      related to homelessness and modifiable health risk factors (poor diet,
      insufficient physical activity, and overweight/obesity) and to provide direction
      for future research. Participants (N = 57) were homeless adults enrolled in a
      smoking cessation program. Analyses were conducted to characterize the sample as
      well as the relations between relevant stressors (discrimination, chronic stress,
      and fear and mistrust) and health risk factors. Inadequate daily consumption of
      fruits, vegetables, and fiber was common. High-fat diet and insufficient physical
      activity were also prevalent, and the majority of participants were
      overweight/obese. Participants commonly endorsed discrimination, fear of
      victimization, mistrust of others, and several other stressors. Greater
      endorsement of stressors was associated with a high-fat diet. Results suggest
      that lifestyle interventions and policy changes may be warranted in homeless
      shelters to attenuate the potential effects of stressors on high-fat dietary
      consumption among smokers. 

PMID- 25616408
TI  - The identification and characterization of non-coding and coding RNAs and their
      modified nucleosides by mass spectrometry.
AB  - The analysis of ribonucleic acids (RNA) by mass spectrometry has been a valuable
      analytical approach for more than 25 years. In fact, mass spectrometry has become
      a method of choice for the analysis of modified nucleosides from RNA isolated out
      of biological samples. This review summarizes recent progress that has been made
      in both nucleoside and oligonucleotide mass spectral analysis. Applications of
      mass spectrometry in the identification, characterization and quantification of
      modified nucleosides are discussed. At the oligonucleotide level, advances in
      modern mass spectrometry approaches combined with the standard RNA modification
      mapping protocol enable the characterization of RNAs of varying lengths ranging
      from low molecular weight short interfering RNAs (siRNAs) to the extremely large
      23 S rRNAs. New variations and improvements to this protocol are reviewed,
      including top-down strategies, as these developments now enable qualitative and
      quantitative measurements of RNA modification patterns in a variety of biological
      systems. 

PMID- 25616411
TI  - African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer
      Screening.
AB  - BACKGROUND: In 2012, the U.S. Preventive Services Task Force released a hotly
      debated recommendation against prostate-specific antigen testing for all men. The
      present research examines African Americans' beliefs about their susceptibility
      to prostate cancer (PCa) and the effectiveness of prostate-specific antigen
      testing in the context of the controversy surrounding this recommendation.
      METHOD: This study used a qualitative design to examine perceptions regarding
      susceptibility and screening. Data were collected at a community health center
      and three predominantly African American churches in North Carolina. Study
      participants were 46 African American men and women who attended one of four
      "listening sessions" for pretesting PCa educational materials (average age = 55
      years). Listening sessions of 1.5-hour duration were conducted to pretest
      materials; while presenting the materials, researchers probed beliefs and
      knowledge about PCa screening. The sessions were recorded and transcribed, and
      the transcripts were qualitatively analyzed using grounded theory. RESULTS: The
      four emergent themes indicated that participants (1) cited behavioral,
      psychosocial, and biological reasons why African American men have higher PCa
      risk compared with others; (2) knew about the controversy and had varying
      responses and intentions; (3) believed screening could save lives, so it should
      be used regardless of the 2012 recommendation; and (4) felt that women can help
      men go to the doctor and make screening decisions. CONCLUSION: Health education
      efforts to help community members understand health controversies, screening
      options, and how to make informed screening decisions are critical.

PMID- 25616412
TI  - Use of Medicare's Diabetes Self-Management Training Benefit.
AB  - Medicare began reimbursing for outpatient diabetes self-management training
      (DSMT) in 2000; however, little is known about program utilization. Individuals
      diagnosed with diabetes in 2010 were identified from a 20% random selection of
      the Medicare fee-for-service population (N = 110,064). Medicare administrative
      and claims files were used to determine DSMT utilization. Multivariate logistic
      regression analyses evaluated the association of demographic, health status, and
      provider availability factors with DSMT utilization. Approximately 5% of Medicare
      beneficiaries with newly diagnosed diabetes used DSMT services. The adjusted odds
      of any utilization were lower among men compared with women, older individuals
      compared with younger, non-Whites compared with Whites, people dually eligible
      for Medicare and Medicaid compared with nondual eligibles, and patients with
      comorbidities compared with individuals without those conditions. Additionally,
      the adjusted odds of utilizing DSMT increased as the availability of providers
      who offered DSMT services increased and varied by Census region. Utilization of
      DSMT among Medicare beneficiaries with newly diagnosed diabetes is low. There
      appear to be marked disparities in access to DSMT by demographic and health
      status factors and availability of DSMT providers. In light of the increasing
      prevalence of diabetes, future research should identify barriers to DSMT access,
      describe DSMT providers, and explore the impact of DSMT services. With preventive
      services being increasingly covered by insurers, the low utilization of DSMT, a
      preventive service benefit that has existed for almost 15 years, highlights the
      challenges that may be encountered to achieve widespread dissemination and uptake
      of the new services. 

PMID- 25616413
TI  - Kv7 channels critically determine coronary artery reactivity: left-right
      differences and down-regulation by hyperglycaemia.
AB  - AIMS: Voltage-gated potassium channels encoded by KCNQ genes (Kv7 channels) are
      emerging as important regulators of vascular tone. In this study, we analysed the
      contribution of Kv7 channels to the vasodilation induced by hypoxia and the
      cyclic AMP pathway in the coronary circulation. We also assessed their regional
      distribution and possible impairment by diabetes. METHODS AND RESULTS: We
      examined the effects of Kv7 channel modulators on K+ currents and vascular
      reactivity in rat left and right coronary arteries (LCAs and RCAs, respectively).
      Currents from LCA were more sensitive to Kv7 channel inhibitors (XE991,
      linopirdine) and activators (flupirtine, retigabine) than those from RCA.
      Accordingly, LCAs were more sensitive than RCAs to the relaxation induced by Kv7
      channel enhancers. Likewise, relaxation induced by the adenylyl cyclase activator
      forskolin and hypoxia, which were mediated through Kv7 channel activation, were
      greater in LCA than in RCA. KCNQ1 and KCNQ5 expression was markedly higher in LCA
      than in RCA. After incubation with high glucose (HG, 30 mmol/L), myocytes from
      LCA, but not from RCA, were more depolarized and showed reduced Kv7 currents. In
      HG-incubated LCA, the effects of Kv7 channel modulators and forskolin were
      diminished, and the expression of KCNQ1 and KCNQ5 was reduced. Finally, vascular
      responses induced by Kv7 channel modulators were impaired in LCA, but not in RCA,
      from type 1 diabetic rats. CONCLUSION: Our results reveal that the high
      expression and function of Kv7 channels in the LCA and their down-regulation by
      diabetes critically determine the sensitivity to key regulators of coronary tone.

PMID- 25616414
TI  - Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation
      regulates cardiac fibrosis.
AB  - AIMS: Methylation of CpG island promoters is a prototypical epigenetic mechanism
      to stably control gene expression. The aim of this study was to elucidate the
      contribution of aberrant promoter DNA methylation in pathological endothelial to
      mesenchymal transition (EndMT) and subsequent cardiac fibrosis. METHODS AND
      RESULTS: In human coronary endothelial cells, TGFbeta1 causes aberrant
      methylation of RASAL1 promoter, increased Ras-GTP activity, and EndMT. In end
      stage failing vs. non-failing human myocardium, increased fibrosis was associated
      with significantly increased RASAL1 promoter methylation, decreased RASAL1
      expression, increased Ras-GTP activity, and increased expression of markers of
      EndMT. In mice with pressure overload due to ascending aortic constriction, BMP7
      significantly reduced RASAL1 promoter methylation, increased RASAL1 expression,
      and decreased EndMT markers as well as decreased cardiac fibrosis. The ten eleven
      translocation (TET) family enzyme TET3, which demethylates through
      hydroxymethylation, was significantly decreased in fibrotic mouse hearts,
      restored with BMP7, and BMP7 effects were absent in coronary endothelial cells
      with siRNA knockdown of TET3. CONCLUSION: Our study provides proof-in-principle
      evidence that transcriptional suppression of RASAL1 through aberrant promoter
      methylation contributes to EndMT and ultimately to progression of cardiac
      fibrosis. Such aberrant methylation can be reversed through Tet3-mediated
      hydroxymethylation, which can be specifically induced by BMP7. This may reflect a
      new treatment strategy to stop cardiac fibrosis.

PMID- 25616415
TI  - Reduction of mouse atherosclerosis by urokinase inhibition or with a limited
      spectrum matrix metalloproteinase inhibitor.
AB  - AIMS: Elevated activity of urokinase plasminogen activator (uPA) and MMPs in
      human arteries is associated with accelerated atherosclerosis, aneurysms, and
      plaque rupture. We used Apoe-null mice with macrophage-specific uPA
      overexpression (SR-uPA mice; a well-characterized model of protease-accelerated
      atherosclerosis) to investigate whether systemic inhibition of proteolytic
      activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis
      and aortic dilation. METHODS AND RESULTS: SR-uPA mice were fed a high-fat diet
      for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1) or a
      control antibody. mU1-treated mice were also compared with PBS-treated non-uPA
      overexpressing Apoe-null mice. Other SR-uPA mice were treated with one of three
      doses of a limited-spectrum synthetic MMP inhibitor (XL784) or vehicle. mU1
      reduced aortic root intimal lesion area (20%; P = 0.05) and aortic root
      circumference (12%; P = 0.01). All XL784 doses reduced aortic root intimal lesion
      area (22-29%) and oil-red-O-positive lesion area (36-42%; P < 0.05 for all doses
      and both end points), with trends towards reduced aortic root circumference (6
      10%). Neither mU1 nor XL784 significantly altered percent aortic surface lesion
      coverage. Several lines of evidence identified MMP-13 as a mediator of uPA
      induced aortic MMP activity. CONCLUSIONS: Pharmacological inhibition of either
      uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition
      decreased aortic dilation. Differential effects of both agents on aortic root vs.
      distal aortic atherosclerosis suggest prevention of atherosclerosis progression
      vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for
      treating atherosclerosis.

PMID- 25616416
TI  - Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage.
AB  - AIMS: Duchenne muscular dystrophy (DMD), a degenerative pathology of skeletal
      muscle, also induces cardiac failure and arrhythmias due to a mutation leading to
      the lack of the protein dystrophin. In cardiac cells, the subsarcolemmal
      localization of dystrophin is thought to protect the membrane from mechanical
      stress. The absence of dystrophin results in an elevated stress-induced Ca2+
      influx due to the inadequate functioning of several proteins, such as stretch
      activated channels (SACs). Our aim was to investigate whether transient receptor
      potential vanilloid channels type 2 (TRPV2) form subunits of the dysregulated
      SACs in cardiac dystrophy. METHODS AND RESULTS: We defined the role of TRPV2
      channels in the abnormal Ca2+ influx of cardiomyocytes isolated from dystrophic
      mdx mice, an established animal model for DMD. In dystrophic cells, western
      blotting showed that TRPV2 was two-fold overexpressed. While normally localized
      intracellularly, in myocytes from mdx mice TRPV2 channels were translocated to
      the sarcolemma and were prominent along the T-tubules, as indicated by
      immunocytochemistry. Membrane localization was confirmed by biotinylation assays.
      Furthermore, in mdx myocytes pharmacological modulators suggested an abnormal
      activity of TRPV2, which has a unique pharmacological profile among TRP channels.
      Confocal imaging showed that these compounds protected the cells from stress
      induced abnormal Ca2+ signals. The involvement of TRPV2 in these signals was
      confirmed by specific pore-blocking antibodies and by small-interfering RNA
      ablation of TRPV2. CONCLUSION: Together, these results establish the involvement
      of TRPV2 in a stretch-activated calcium influx pathway in dystrophic
      cardiomyopathy, contributing to the defective cellular Ca2+ handling in this
      disease.

PMID- 25616417
TI  - Functional assessment of intrinsic disorder central domains of BRCA1.
AB  - The most studied function of BRCA1 is that of tumor suppression through its role
      in DNA repair and transcription regulation. Germline mutations discovered in a
      larger cohort of patients, abrogate BRCA1 interactions with reported cellular
      partners, and are responsible for breast and ovarian cancer. The different
      functional regions of BRCA1 interact with nearly 30 different cellular partners.
      Thus, it becomes clinically significant to understand the detailed protein
      protein interactions associated with functional regions of BRCA1. Different
      overlapping central domains of BRCA1 have been characterized using in silico, in
      vitro and biophysical approaches. To our conclusions, it has been observed that
      central domains of BRCA1 are intrinsically disordered and has large hydrodynamic
      radius with random coil like structures. 

PMID- 25616419
TI  - Heart Rate Variability in Breast Cancer Survivors After the First Year of
      Treatments: A Case-Controlled Study.
AB  - The same aggressive treatments that have led to a reduction in the breast cancer
      may also have adverse effects on cardiac autonomic balance. The objective of this
      study was to compare heart rate variability (HRV) between breast cancer survivors
      in the first year posttreatment and healthy women, controlling for known
      confounders. This descriptive case-controlled study included 22 breast cancer
      survivors and 22 healthy age- and sex-matched controls. Short-term HRV was
      measured using an accepted methodology to assess the cardiac autonomic balance.
      One-way analysis of covariance results revealed that heart rate was significantly
      higher (F = 15.86, p < .001) and the standard deviation of normal-to-normal (NN)
      interval (F = 19.93, p = .001), square root of mean squared differences of
      successive NN intervals (F = 18.72, p = .001), HRV index (F = 5.44, p = .025),
      and high-frequency (F = 5.77, p = .03) values were significantly lower in the
      breast cancer survivors than in the matched controls. The principal finding of
      the presence of a cardiovascular imbalance in breast cancer survivors in
      comparison to healthy age-matched controls suggests that HRV study could be a
      clinically useful tool to detect cardiovascular disease in early-stage breast
      cancer survivors. 

PMID- 25616418
TI  - GSK3 inhibitors stabilize Wee1 and reduce cerebellar granule cell progenitor
      proliferation.
AB  - Ubiquitin mediated proteolysis is required for transition from one cell cycle
      phase to another. For instance, the mitosis inhibitor Wee1 is targeted for
      degradation during S phase and G2 to allow mitotic entry. Wee1 is an essential
      tyrosine kinase required for the G2/M transition and S-phase progression.
      Although several studies have concentrated on Wee1 regulation during mitosis, few
      have elucidated its degradation during interphase. Our prior studies have
      demonstrated that Wee1 is degraded via CK1delta dependent phosphorylation during
      the S and G2/M phases of the cell cycle. Here we demonstrate that GSK3beta may
      work in concert with CK1delta to induce Wee1 destruction during interphase. We
      generated small molecules that specifically stabilized Wee1. We profiled these
      compounds against 296 kinases and found that they inhibit GSK3alpha and GSK3beta,
      suggesting that Wee1 may be targeted for proteolysis by GSK3. Consistent with
      this notion, known GSK3 inhibitors stabilized Wee1 and GSK3beta depletion reduced
      Wee1 turnover. Given Wee1's central role in cell cycle progression, we predicted
      that GSK3 inhibitors should limit cell proliferation. Indeed, we demonstrate that
      GSK3 inhibitors potently inhibited proliferation of the most abundant cell in the
      mammalian brain, the cerebellar granule cell progenitor (GCP). These studies
      identify a previously unappreciated role for GSK3beta mediated regulation of Wee1
      during the cell cycle and in neurogenesis. Furthermore, they suggest that
      pharmacological inhibition of Wee1 may be therapeutically attractive in some
      cancers where GSK-3beta or Wee1 are dysregulated. 

PMID- 25616421
TI  - The associations between adult attachment, posttraumatic symptoms, and
      posttraumatic growth.
AB  - BACKGROUND AND OBJECTIVES: Individual differences after trauma vary considerably
      and can range from posttraumatic stress disorder (PTSD) to posttraumatic growth
      (PTG). Current theoretical models cannot fully explain this variability.
      Therefore, we integrated attachment theory with Ehlers and Clark's model of PTSD
      to understand whether attachment style is associated with negative appraisals of
      a traumatic event(s), posttraumatic stress symptoms (PTS), and PTG. Our aim was
      to test this integrated model PTSD in an analog sample who had experienced at
      least one traumatic event. DESIGN: We used structural equation modeling to test
      the association of adult attachment and posttraumatic cognitions (self and
      world/others) with PTS and PTG using a cross-sectional, correlational design.
      METHODS: The sample comprised 393 university staff and students (RangeAge= 18-49,
      85% females) who completed online measures. RESULTS: Attachment anxiety and
      negative posttraumatic self-cognitions were positively associated. Negative
      posttraumatic self-cognitions were positively associated with PTS. Attachment
      anxiety had an indirect effect (via negative posttraumatic self-cognitions) on
      PTS, whereas attachment avoidance predicted more negative posttraumatic world
      cognitions and lower perceived PTG. CONCLUSIONS: The study highlights the
      importance of considering how attachment styles influence posttraumatic emotion
      regulation and cognitive processing of the trauma to determine posttraumatic
      mental health.

PMID- 25616422
TI  - Quantifying treatment effects in randomised controlled trials.

PMID- 25616423
TI  - Ebola vaccine to be tested on 30,000 volunteers.

PMID- 25616424
TI  - Economic difficulties and subsequent disability retirement.
AB  - BACKGROUND: This study examined whether economic difficulties are associated with
      subsequent disability retirement while controlling for covariates. METHODS:
      Survey data among middle-aged employees of the City of Helsinki in 2000-2002 were
      linked with the Finnish Centre for Pensions register data on all-cause disability
      retirement among women (n=4816) and men (n=1354) until the end of 2010.
      Additionally, disability retirement due to musculoskeletal diseases and mental
      disorders (ICD-10) was examined among women. Frequency in difficulties paying
      pills and buying food and clothes, and covariates (occupational class, income,
      housing tenure, and work- and health-related covariates) were self-reported at
      baseline. Hazard ratios (HR) and their 95% confidence intervals (95% CI) were
      calculated from Cox regression analysis. RESULTS: Frequent economic difficulties
      were associated with all-cause disability retirement after adjusting for age
      among both women (HR=2.11; 95% CI 1.63-2.73) and men (HR=2.69; 95% CI 1.65-4.41).
      Adjustment for covariates somewhat attenuated the associations, but they
      remained. Economic difficulties were also associated with disability retirement
      due to both mental disorders (HR=3.29; 95% CI 1.98-5.46) and musculoskeletal
      diseases (HR=1.85; 95% CI 1.24-2.75) among women. Adjustments made a minor
      contribution to the risk of disability retirement due to mental disorders,
      whereas the risk of disability retirement due to musculoskeletal diseases reduced
      after considering socioeconomic circumstances. Conclusions: economic difficulties
      are independently associated with disability retirement. Thus, they should be
      considered in attempts to tackle early exit from the labour market due to
      disability.

PMID- 25616425
TI  - Relevance of P-glycoprotein in stroke prevention with dabigatran, rivaroxaban,
      and apixaban.
AB  - BACKGROUND: The new oral anticoagulants (NOAC) dabigatran etexilate, rivaroxaban,
      and apixaban show similar efficacy for stroke prevention in patients with atrial
      fibrillation (AF) as the vitamin K antagonist warfarin. Absorption of NOACs is
      dependent on the intestinal P-glycoprotein (P-gp) system and P-gp activity is
      modulated by a variety of drugs and food components. OBJECTIVE: The aim of this
      review is to give an overview of P-gp-associated drug-drug and drug-food
      interactions with NOACs in AF patients. METHODS: A literature search was carried
      out by screening MEDLINE for the terms dabigatran, rivaroxaban, apixaban, P
      glycoprotein, and atrial fibrillation from 1998 to 2013. Randomized clinical
      trials, longitudinal studies, case series, and case reports were included.
      RESULTS: Concomitant medication with proton pump inhibitors, amiodarone,
      clarithromycin, and verapamil increased bioavailability whereas rifampicin
      decreased the bioavailability of dabigatran. Coadministration of erythromycin,
      clarithromycin, fluconazole, ketoconazole, and ritonavir increased rivaroxaban
      plasma concentrations. No data were found on apixaban and P-gp-modulating drugs
      or on NOACs and food components modulating P-gp. The clinical relevance of
      interactions between NOACs and P-gp-modulating drugs or food components is
      largely unknown as bleeding complications under NOACs and P-gp-inhibiting drugs
      are mainly reported from patients with concomitant renal failure. CONCLUSION:
      There is an urgent need to investigate the role of P-gp-modulating substances as
      potential sources of drug-drug and drug-food interactions. A thorough analysis of
      the data accumulated in the three large NOAC trials regarding the role of P-gp
      modulating drugs in bleeding and embolic events is desirable. Pharmacological
      studies should investigate the influence of P-gp-modulating drugs and food on
      NOAC plasma concentrations and coagulation parameters. When prescribing NOACs,
      patients should be informed about the potential interactions with drugs and
      herbal drugs. Patients who develop bleeding or embolic events under treatment
      with NOACs should be investigated for co-medications as well as for over-the
      counter drugs and dietary habits. In post-marketing surveillance of NOACs, the
      association with drug or food intake with complications, bleeding, and embolic
      events should be registered.

PMID- 25616427
TI  - Coping with infertility: Comparison of coping mechanisms and psychological immune
      competence in fertile and infertile couples.
AB  - This study compared coping strategies and psychological immunity of parents with
      a child conceived with assisted reproductive technology (n = 84) and parents with
      a naturally conceived child (n = 84) in a Hungarian fertility-age population.
      Results showed that in vitro fertilization parents are able to control their
      emotions in a better way than comparison couples. They interpret trials as
      challenges and consider themselves more worthy than the members of the control
      group. Our research confirms that consideration and management of psychological
      factors in treating infertility have an important preventive role to play.

PMID- 25616426
TI  - Statistics on the use of cardiac electronic devices and electrophysiological
      procedures in the European Society of Cardiology countries: 2014 report from the
      European Heart Rhythm Association.
AB  - AIMS: There has been large variations in the use of invasive electrophysiological
      therapies in the member countries of the European Society of Cardiology (ESC).
      The aim of this analysis was to provide comprehensive information on cardiac
      implantable electronic device (CIED) and catheter ablation therapy trends in the
      ESC countries over the last five years. METHODS: The European Heart Rhythm
      Association (EHRA) has collected data on CIED and catheter ablation therapy since
      2008. Last year 49 of the 56 ESC member countries provided data for the EHRA
      White Book. This analysis is based on the current and previous editions of the
      EHRA White Book. Data on procedure rates together with information on economic
      aspects, local reimbursement systems and training activities are presented for
      each ESC country and the five geographical ESC regions. RESULTS: In 2013, the
      electrophysiological procedure rates per million population were highest in
      Western Europe followed by the Southern and Northern European countries. The CIED
      implantation and catheter ablation rate was lowest in the Eastern European and in
      the non-European ESC countries, respectively. However, in some Eastern European
      countries with relative low gross domestic product procedure rates exceeded those
      of some wealthier Western countries, suggesting that economic resources are not
      the only driver for utilization of arrhythmia therapies. CONCLUSION: These
      statistics indicate that despite significant improvements, there still is
      considerable heterogeneity in the availability of arrhythmia therapies across the
      ESC area. Hopefully, these data will help identify areas for improvement and
      guide future activities in cardiac arrhythmia management.

PMID- 25616428
TI  - UK moves to legislate on standardised cigarette packaging before election.

PMID- 25616429
TI  - Relationship between admission blood glucose level and prognosis in elderly
      patients without previously known diabetes who undergo emergency non-cardiac
      surgery.
AB  - Elevated blood glucose levels on admission are important as a marker for adverse
      events in patients who undergo surgery. This study aims to evaluate the
      relationship between admission glucose level and adverse outcome during the 30
      day follow-up period in elderly patients without previously known diabetes who
      undergo emergency non-cardiac surgery. The primary and secondary end points were
      all-cause and major adverse cardiac event (MACE) mortalities, respectively,
      during the 30-day postoperative follow-up period. Higher 30-day all-cause (24.1
      %) and MACE (13.7 %) mortalities were observed in patients with an admission
      glucose >= 11.1 mmol/L than in patients with admission glucose <11.1 mmol/L (p <
      0.001). Multivariate logistic regression analysis shows that an higher admission
      blood glucose level is an independent predictor for the development of the 30-day
      all-cause mortality [odds ratio (OR), 1.91; 95 % confidence interval (CI), 1.746
      2.082; p < 0.001) and cardiac mortality (OR 1.97, 95 % CI 1.774-2.191; p < 0.001]
      after adjusting for age, gender, body mass index, comorbidities, and medication
      before admission. Kaplan-Meier event-free survival curves demonstrate that an
      admission blood glucose level >= 11.1 mmol/L has worse event-free survival than
      an admission blood glucose level <11.1 mmol/L.

PMID- 25616430
TI  - A randomized phase II study of carboplatin with weekly or every-3-week
      nanoparticle albumin-bound paclitaxel (abraxane) in patients with extensive-stage
      small cell lung cancer.
AB  - BACKGROUND: Platinum plus etoposide is the standard therapy for extensive-stage
      small cell lung cancer (ES-SCLC) and is associated with significant
      myelosuppression. We hypothesized that the combination of carboplatin and
      nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated.
      We investigated carboplatin with nab-paclitaxel on every-3-week and weekly
      schedules. METHODS: This noncomparative randomized phase II trial used a two
      stage design. The primary objective was objective response rate, and secondary
      objectives were progression-free survival, overall survival, and toxicity.
      Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance
      status <=2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A
      (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300
      mg/m(2) on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab
      paclitaxel 100 mg/m(2) on days 1, 8, and 15 every 21 days). Response was assessed
      after every two cycles. RESULTS: Patients required frequent dose reductions,
      treatment delays, and omission of the weekly therapy. The trial was closed
      because of slow accrual. CONCLUSION: Carboplatin and nab-paclitaxel demonstrated
      activity in ES-SCLC but required frequent dose adjustments.

PMID- 25616431
TI  - The European Medicines Agency approval of axitinib (Inlyta) for the treatment of
      advanced renal cell carcinoma after failure of prior treatment with sunitinib or
      a cytokine: summary of the scientific assessment of the committee for medicinal
      products for human use.
AB  - Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor
      receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3. Based on the positive opinion from
      the European Medicines Agency (EMA), a marketing authorization valid throughout
      the European Union (EU) was issued for the treatment of advanced renal cell
      carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine.
      The demonstration of clinical benefit for axitinib was based on a phase III,
      randomized, open-label, multicenter study of axitinib compared with sorafenib in
      patients with advanced RCC after failure of a prior systemic first-line regimen
      containing one or more of the following agents: sunitinib, bevacizumab plus
      interferon-alpha, temsirolimus, or cytokines. In the primary analysis, a 2-month
      increase in median progression-free survival (PFS) was observed for axitinib
      compared with sorafenib (hazard ratio [HR]: 0.665; 95% confidence interval [CI]:
      0.544-0.812; p < .0001). In the subgroup of patients with a prior cytokine
      containing regimen, the increase in median PFS associated with axitinib was 5.4
      months (updated analysis, HR: 0.519; 95% CI: 0.375-0.720; p < .0001). In the
      subgroup of patients with prior sunitinib treatment, the increase in median PFS
      was 1.4 months (updated analysis, HR: 0.736; 95% CI: 0.578-0.937; p = .0063). The
      analysis of overall survival showed no statistically significant survival benefit
      of axitinib over sorafenib in patients previously treated with cytokine
      containing regimens (HR: 0.813; 95% CI: 0.556-1.191) or sunitinib (HR: 0.997; 95%
      CI: 0.782-1.270). The most common treatment-related adverse events associated
      with axitinib included diarrhea, hypertension, fatigue, nausea, decreased
      appetite, dysphonia, and palmar-plantar erythrodysesthesia. Most of these events
      were mild or moderate in severity. This paper summarizes the scientific review of
      the application leading to approval in the EU. The detailed scientific assessment
      report and product information, including the summary of product characteristics,
      are available on the EMA website (http://www.ema.europa.eu). 

PMID- 25616433
TI  - Less than a 10th of China's couples apply to have second child.

PMID- 25616432
TI  - Differentiated thyroid cancer: focus on emerging treatments for radioactive
      iodine-refractory patients.
AB  - BACKGROUND: The treatment of differentiated thyroid cancer refractory to
      radioactive iodine (RAI) had been hampered by few effective therapies. Recently,
      tyrosine kinase inhibitors (TKIs) have shown activity in this disease. Clinical
      guidance on the use of these agents in RAI-refractory thyroid cancer is
      warranted. MATERIALS AND METHODS: Molecular mutations found in RAI-refractory
      thyroid cancer are summarized. Recent phase II and III clinical trial data for
      TKIs axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, and
      vandetinib are reviewed including efficacy and side effect profiles. Molecular
      targets and potencies of these agents are compared. Inhibitors of BRAF, mammalian
      target of rapamycin, and MEK are considered. RESULTS: Routine testing for
      molecular alterations prior to therapy is not yet recommended. TKIs produce
      progression-free survival of approximately 1 year (range: 7.7-19.6 months) and
      partial response rates of up to 50% by Response Evaluation Criteria in Solid
      Tumors. Pazopanib and lenvatinib are the most active agents. The majority of
      patients experienced tumor shrinkage with TKIs. Common adverse toxicities affect
      dermatologic, gastrointestinal, and cardiovascular systems. CONCLUSION: Multiple
      TKIs have activity in RAI-refractory differentiated thyroid cancer. Selection of
      a targeted agent should depend on disease trajectory, side effect profile, and
      goals of therapy.

PMID- 25616434
TI  - Olaparib: first global approval.
AB  - Olaparib (LynparzaTM) is an oral, small molecule, poly (ADP-ribose) polymerase
      inhibitor being developed by AstraZeneca for the treatment of solid tumours. The
      primary indication that olaparib is being developed for is BRCA mutation-positive
      ovarian cancer. A capsule formulation of the drug has received approval for use
      in this setting in the EU and USA, and a tablet formulation is in global phase
      III trials (including in the USA, EU, Australia, Brazil, Canada, China, Israel,
      Japan, Russia and South Korea). In addition, phase III trials in breast, gastric
      and pancreatic cancer are underway/planned, and phase I/II investigation is being
      conducted in other malignancies, including prostate cancer, non-small cell lung
      cancer, Ewing's sarcoma and advanced cancer. This article summarizes the
      milestones in the development of olaparib leading to this first approval for
      ovarian cancer.

PMID- 25616436
TI  - Decreased production of higher alcohols by Saccharomyces cerevisiae for Chinese
      rice wine fermentation by deletion of Bat aminotransferases.
AB  - An appropriate level of higher alcohols produced by yeast during the fermentation
      is one of the most important factors influencing Chinese rice wine quality. In
      this study, BAT1 and BAT2 single- and double-gene-deletion mutant strains were
      constructed from an industrial yeast strain RY1 to decrease higher alcohols
      during Chinese rice wine fermentation. The results showed that the BAT2 single
      gene-deletion mutant strain produced best improvement in the production of higher
      alcohols while remaining showed normal growth and fermentation characteristics.
      Furthermore, a BAT2 single-gene-deletion diploid engineered strain RY1-Deltabat2
      was constructed and produced low levels of isobutanol and isoamylol (isoamyl
      alcohol and active amyl alcohol) in simulated fermentation of Chinese rice wine,
      92.40 and 303.31 mg/L, respectively, which were 33.00 and 14.20 % lower than
      those of the parental strain RY1. The differences in fermentation performance
      between RY1-Deltabat2 and RY1 were minor. Therefore, construction of this yeast
      strain is important in future development in Chinese wine industry and provides
      insights on generating yeast strains for other fermented alcoholic beverages. 

PMID- 25616435
TI  - Types and effects of protein variations.
AB  - Variations in proteins have very large number of diverse effects affecting
      sequence, structure, stability, interactions, activity, abundance and other
      properties. Although protein-coding exons cover just over 1 % of the human genome
      they harbor an disproportionately large portion of disease-causing variants.
      Variation ontology (VariO) has been developed for annotation and description of
      variation effects, mechanisms and consequences. A holistic view for variations in
      proteins is made available along with examples of real cases. Protein variants
      can be of genetic origin or emerge at protein level. Systematic names are
      provided for all variation types, a more detailed description can be made by
      explaining changes to protein function, structure and properties. Examples are
      provided for the effects and mechanisms, usually in relation to human diseases.
      In addition, the examples are selected so that protein 3D structural changes,
      when relevant, are included and visualized. Here, systematics is described for
      protein variants based on VariO. It will benefit the unequivocal description of
      variations and their effects and further reuse and integration of data from
      different sources.

PMID- 25616437
TI  - Modification of CETP function by changing its substrate preference: a new
      paradigm for CETP drug design.
AB  - We previously determined that hamster cholesteryl ester transfer protein (CETP),
      unlike human CETP, promotes a novel one-way transfer of TG from VLDL to HDL,
      causing HDL to gain lipid. We hypothesize that this nonreciprocal lipid transfer
      activity arises from the usually high TG/cholesteryl ester (CE) substrate
      preference of hamster CETP. Consistent with this, we report here that ~25% of the
      total lipid transfer promoted by the human Q199A CETP mutant, which prefers TG as
      substrate, is nonreciprocal transfer. Other human CETP mutants with TG/CE
      substrate preferences higher or lower than wild-type also possess nonreciprocal
      lipid transfer activity. Mutants with high TG/CE substrate preference promote the
      nonreciprocal lipid transfer of TG from VLDL to HDL, but mutants with low TG/CE
      substrate preference promote the nonreciprocal lipid transfer of CE, not TG, and
      this lipid flow is in the reverse direction (from HDL to VLDL). Anti-CETP TP2
      antibody alters the TG/CE substrate preference of CETP and also changes the
      extent of nonreciprocal lipid transfer, showing the potential for externally
      acting agents to modify the transfer properties of CETP. Overall, these data show
      that the lipid transfer properties of CETP can be manipulated. Function-altering
      pharmaceuticals may offer a novel approach to modify CETP activity and achieve
      specific modifications in lipoprotein metabolism. 

PMID- 25616439
TI  - Improving adolescent sexual and reproductive health in Latin America: reflections
      from an International Congress.
AB  - In February 2014, an international congress on Promoting Adolescent Sexual and
      Reproductive Health (ASRH) took place in Cuenca, Ecuador. Its objective was to
      share evidence on effective ASRH intervention projects and programs in Latin
      America, and to link this evidence to ASRH policy and program development. Over
      800 people participated in the three-day event and sixty-six presentations were
      presented.This paper summarizes the key points of the Congress and of the
      Community Embedded Reproductive Health Care for Adolescents (CERCA) project. It
      aims at guiding future ASRH research and policy in Latin America. 1. Context
      matters. Individual behaviors are strongly influenced by the social context in
      which they occur, through determinants at the individual, relational, family,
      community and societal levels. Gender norms/attitudes and ease of communication
      are two key determinants. 2. Innovative action. There is limited and patchy
      evidence of effective approaches to reach adolescents with the health
      interventions they need at scale. Yet, there exist several promising and
      innovative examples of providing comprehensive sexuality education through
      conventional approaches and using new media, improving access to health services,
      and reaching adolescents as well as families and community members using
      community-based interventions were presented at the Congress. 3. Better
      measurement. Evaluation designs and indicators chosen to measure the effect and
      impact of interventions are not always sensitive to subtle and incremental
      changes. This can create a gap between measured effectiveness and the impact
      perceived by the targeted populations. Thus, one conclusion is that we need more
      evidence to better determine the factors impeding progress in ASRH in Latin
      American, to innovate and respond flexibly to changing social dynamics and
      cultural practices, and to better measure the impact of existing intervention
      strategies. Yet, this Congress offered a starting point from which to build a
      multi-agency and multi-country effort to generate specific evidence on ASRH with
      the aim of guiding policy and program decision-making. In a region that contains
      substantial barriers of access to ASRH education and services, and some of the
      highest adolescent pregnancy rates in the world, the participants agreed that
      there is no time to lose.

PMID- 25616438
TI  - Effects of n-3 FA supplementation on the release of proresolving lipid mediators
      by blood mononuclear cells: the OmegAD study.
AB  - Specialized proresolving mediators (SPMs) induce resolution of inflammation. SPMs
      are derivatives of n-3 and n-6 PUFAs and may mediate their beneficial effects. It
      is unknown whether supplementation with PUFAs influences the production of SPMs.
      Alzheimer's disease (AD) is associated with brain inflammation and reduced levels
      of SPMs. The OmegAD study is a randomized, double-blind, and placebo-controlled
      clinical trial on AD patients, in which placebo or a supplement of 1.7 g DHA and
      0.6 g EPA was taken daily for 6 months. Plasma levels of arachidonic acid
      decreased, and DHA and EPA levels increased after 6 months of n-3 FA treatment.
      Peripheral blood mononuclear cells (PBMCs) were obtained before and after the
      trial. Analysis of the culture medium of PBMCs incubated with amyloid-beta 1-40
      showed unchanged levels of the SPMs lipoxin A4 and resolvin D1 in the group
      supplemented with n-3 FAs, whereas a decrease was seen in the placebo group. The
      changes in SPMs showed correspondence to cognitive changes. Changes in the levels
      of SPMs were positively correlated to changes in transthyretin. We conclude that
      supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs
      released from PBMCs of AD patients, which was associated with changes in
      cognitive function. 

PMID- 25616440
TI  - Graduate entry and undergraduate medical students' study approaches, stress
      levels and ways of coping: a five year longitudinal study.
AB  - BACKGROUND: Incorporating graduate students into undergraduate medical degree
      programs is a commonly accepted practice. However, it has only recently been
      recognized that these two types of students cope with their studies in various
      ways. The aim was to compare the learning approaches, stress levels and ways of
      coping of undergraduate (UG) and graduate entry medical students (GEMP)
      throughout their medical course. METHODS: From 2007-2011 each of the five year
      cohorts of undergraduate and GEMP students completed four components of the
      study. The components included demographics, The Biggs' R-SPQ-2 F questionnaire
      which determines students' approaches to learning, the Perceived Stress Scale
      (PSS) used to rate students perceived stress during the past four weeks, and the
      Ways of Coping (WOC) questionnaire used to assess students' methods of coping
      with everyday problems. RESULTS: There was a consistent difference between UG and
      GEMP students approaches to learning over the five years. GEMP students preferred
      a deep approach while the UG students preferred a superficial approach to
      learning. This difference became more obvious in the clinical years. There was no
      statistically significant difference between the groups in stress levels. There
      were consistent differences in the ways the two groups coped with stress.
      CONCLUSIONS: There were significant differences in approaches to learning and
      ways of coping with stress between the UG and the GEMP students. These need to be
      considered when introducing curriculum change, in particular, redesigning an UG
      program for post graduate delivery.

PMID- 25616441
TI  - Estrogen Activates AMP-Activated Protein Kinase in Human Endothelial Cells via
      ERbeta/Ca(2+)/Calmodulin-Dependent Protein Kinase Kinase beta Pathway.
AB  - Our previous studies suggested that Estrogen inhibits cytokine-induced expression
      of VCAM-1 and ICAM-1 in cultured human endothelial cells via AMP-activated
      protein kinase (AMPK) activation. Here, we sought to delineate the mechanisms
      underlying estrogen activation of AMPK. AMPK can be considered a 'fuel gauge' of
      cellular energy status in response to metabolic stress. It is controlled by
      upstream kinases such as Ca(2+)/calmodulin-dependent protein kinase kinase beta
      (CaMKKbeta) or LKB1. The present study of human endothelial cells demonstrates
      that AMPK is activated by estradiol (E2) through a Ca(2+)-dependent mechanism
      involving the estrogen receptor-beta (ERbeta) activation. Inhibition of CaMKK
      with STO-609, a specific inhibitor of CaMKKalpha and CaMKKbeta, attenuated E2
      induced AMPK activation, suggesting that CaMKKbeta was the responsible AMPK
      kinase. Conversely, down-regulation of LKB1 did not affect E2-induced AMPK
      activation. E2 stimulation caused phosphorylation of acetyl coenzyme A
      carboxylase (ACC) and endothelial nitric oxide synthase (eNOS), two main targets
      of AMPK. Inhibition or down-regulation of CaMKKbeta eliminated phosphorylation of
      ACC and eNOS in response to E2. Together, our data highlight the role of Ca(2+)
      as a regulator of AMPK activation in response to E2 stimulation. We demonstrate
      that E2 activates AMPK via an ERbeta/Ca(2+)/CaMKKbeta-dependent pathway in
      endothelial cells. 

PMID- 25616442
TI  - The Endothelium as a Target for the Treatment of Heart Failure.
AB  - The functional integrity of endothelial cells is a marker and a prerequisite for
      vascular health. It is well established that the endothelium not only modulates,
      but also mediates vascular disease processes. Certain diseases such as diabetes,
      dyslipidaemia, obesity, and arterial hypertension advance endothelial injury. The
      disease process induces cellular and functional changes in endothelial cells
      leading to a pathophysiological phenomenon referred to as endothelial cell
      dysfunction, which involves abnormal vasomotion, an imbalance in reactive oxygen
      species and nitric oxide, the activation of inflammation, and disruption of the
      coagulation process of the endothelial cells. With this knowledge, it is now
      known that vascular function plays a central role in the development and
      progression of heart failure (HF). HF is the primary cause of patient
      hospitalization. There is a strong desire to intervene and prevent the growing HF
      epidemic. Over the last decade, numerous therapies have been evaluated but few
      have led to positive results in the later stages of clinical trials. Efforts are
      currently being made to understand the pathophysiology of endothelial dysfunction
      and use this knowledge to identify novel agents or therapeutic targets that will
      improve the outcome of patients with HF and restore the normal function of the
      endothelium. The purpose of this review is to present a brief summary of the
      traditional approaches that have been taken to improve endothelial dysfunction
      and combat HF and, more importantly, to discuss some novel therapeutic approaches
      that are still under investigation, including the use of gene therapy and
      nanocarriers as means of delivering targets to the dysfunctional endothelium as
      treatment for HF. 

PMID- 25616443
TI  - "Getting tested is almost like going to the Salem witch trials": discordant
      discourses between Western public health messages and sociocultural expectations
      surrounding HIV testing among East African immigrant women.
AB  - Washington, DC, has the highest AIDS diagnosis rate in the USA, and Black women
      are disproportionately affected. Although HIV testing is the first entryway into
      vital treatment services, evidence reveals that foreign-born blacks have a lower
      rate of recent HIV testing than US-born blacks. To date, however, there are no
      studies that examine the culture-specific perceptions of HIV testing among East
      African immigrant women (who comprise a large share of Black Africans in DC) to
      better understand their potential barriers to testing. Adopting the PEN-3
      cultural model as our theoretical framework, the main objective of this study was
      to examine East African women's HIV testing perceptions and partner communication
      norms. Between October 2012 and March 2013, trained interviewers conducted a
      total of 25 interviews with East African women in the Washington, DC,
      metropolitan area. For triangulation purposes, data collection consisted of both
      in-depth, semi-structured interviews and cognitive interviews, in which
      participants were administered a quantitative survey and assessed on how they
      interpreted items. Qualitative thematic analysis revealed a systematic pattern of
      discordant responses across participants. While they were aware of messages
      related to Western public health discourse surrounding HIV testing (e.g.,
      Everyone should get tested for HIV; One should talk to one's spouse about HIV
      testing), divergent sociocultural expectations rooted in cultural and religious
      beliefs prevailed (e.g., Getting an HIV test brings shame to the person who got
      tested and to one's family; it implies one is engaging in immoral behavior; One
      should not talk with one's spouse about HIV testing; doing so breaks cultural
      norms). Implications of using a culture-centered model to examine the role of
      sociocultural expectations in HIV prevention research and to develop culturally
      responsive prevention strategies are discussed. 

PMID- 25616444
TI  - Risk factors and safe dosage of levodopa for wearing-off phenomenon in Chinese
      patients with Parkinson's disease.
AB  - The objective of this study was to investigate the risk factors of wearing-off
      phenomenon in Parkinson's disease (PD) and propose safe dosage of levodopa to
      reduce wearing-off development based on Chinese cohort. Patients with PD who had
      taken levodopa (L-dopa) for at least 1 month were recruited. Wearing-off was
      diagnosed based on validated Chinese version of a patient self-rated 9-question
      Wearing-Off Questionnaire (WOQ-9) and clinical definition. Eleven variables
      (gender, disease duration at L-dopa initiation, disease duration at assessment,
      age at onset, age at assessment, H-Y stage, UPDRS III, L-dopa daily total dosage
      and dosage adjusted to weight, duration of L-dopa treatment, initial drug recipe)
      were included in our analysis. Univariate analysis, multivariate logistic
      regression analysis and decision tree classification model(DTC) were used to
      detect risk factors of wearing-off. Receiver operating characteristic (ROC) curve
      and DTC were used to investigate cut-off value of L-dopa to best predict wearing
      off. Two hundred and thirty-four patients were investigated in our study, among
      whom 111 developed wearing-off. Patients with wearing-off tended to receive
      higher L-dopa dosage and endure longer duration of L-dopa treatment. L-Dopa
      dosage as 281 mg/day and 4.2 mg/kg/day by ROC, as well as 269 mg/day and 3.2
      mg/kg/day by DTC were cut-off values for wearing-off. L-Dopa dosage and duration
      of L-dopa treatment were related to increased wearing-off development. Cumulative
      L-dopa dosage and L-dopa daily dosage were better predictive of wearing-off.
      Inadequate evidence was present for delayed L-dopa initiation. L-Dopa daily
      dosage no more than 275 mg or 4.2 mg/kg was regarded as safe.

PMID- 25616445
TI  - Recommendations from the Italian Interdisciplinary Working Group (AIMN, AIP,
      SINDEM) for the utilization of amyloid imaging in clinical practice.
AB  - Positron emission tomography (PET) of brain amyloid is a technology that has been
      approved by Food and Drug Administration and European Medical Agency, but its
      clinical utility in medical practice requires careful definition. To provide
      guidance to italian dementia care practitioners, patients, and caregivers, a
      group of experts from "Associazione Italiana di Medicina Nucleare" (AIMN),
      "Associazione Italiana di Psicogeriatria" (AIP) and "Societa Italiana per lo
      Studio delle Demenze" (SINDEM) convened the Italian Interdisciplinary Working
      Group on Amyloid Imaging. The Working Group considered a range of clinical
      scenarios in which amyloid PET should be recommended. Peer-reviewed, published
      literature was searched to ascertain available evidence relevant to these
      recommendations. Although empirical evidence of impact on clinical outcomes is
      not yet available, a set of specific recommended use criteria were agreed to
      define the types of patients and clinical circumstances in which amyloid PET
      could be used. Both correct and incorrect uses were considered and formulated.
      Because both dementia care and amyloid-PET technology are in active development,
      these recommendations will require periodic reassessment.

PMID- 25616446
TI  - Treatment of Raynaud's phenomenon with botulinum toxin type A.
AB  - Raynaud's phenomenon (RP), an episodic vasospasm of the peripheral arteries, is
      quite common in general population. The current therapies of RP are limited by
      efficacy, side effects, and polypharmacy concerns. Botulinum toxin type A (BTX-A)
      local injections have been reported for the treatment of RP, but the injection
      sites, concentration and dose of BTX-A were different from each other in previous
      trials. In addition, so far, there have been no reports concerning local
      injection of BTX-A in Asian RP patients. Ten patients with RP in China were
      included in this retrospective study. All the patients had intractable pain and
      were non-responsive to conservative and/or medical therapy. A patterned BTX-A
      injection was performed in RP patients, guided by ultrasonography. BTX-A was
      injected as 20 u/ml devoid of preservatives. Outcomes were measured by
      ultrasonography, surface temperature, visual analog scale (VAS) for clinical
      symptoms (pain, numbness, stiffness and swelling), and changes in ulcers or
      gangrene. Overall, a great improvement in artery flow velocity (P < 0.01),
      surface temperature (P < 0.01), ulcer and VAS for clinical symptoms, was observed
      after BTX-A local injection. Complications were very rarely found, and no
      patients complained of hand weakness and bruise. BTX-A patterned injection guided
      by ultrasonography might be a useful therapeutic tool in the management of
      intractable RP.

PMID- 25616447
TI  - Marine fish oils are not equivalent with respect to B-cell membrane organization
      and activation.
AB  - We previously reported that docosahexaenoic-acid (DHA)-enriched fish oil (DFO)
      feeding altered B-cell membrane organization and enhanced B-cell function. The
      purpose of this study was to evaluate whether menhaden oil (MO) and
      eicosapentaenoic-acid (EPA)-enriched fish oil (EFO) alters B-cell
      function/phenotype similarly. Mice were fed control (CON), MO, EFO or DFO diets
      for 5weeks. We evaluated the fatty acid composition of B-cell phospholipids,
      membrane microdomain organization, ex vivo B-cell functionality and in vivo B
      cell subsets. Red blood cells and B cells were found to be strongly (r>0.85) and
      significantly (P<.001) correlated for major n-3 and n-6 long-chain
      polyunsaturated fatty acids (LCPUFAs). Compared to CON, MO and DFO resulted in
      decreased clustering of membrane microdomains, whereas EFO increased clustering.
      All fish oil treatments had 1.12-1.60 times higher CD40 expression following
      stimulation; however, we observed 0.86 times lower major histocompatibility
      complex class II expression and 0.7 times lower interleukin (IL)-6 production
      from EFO, but 3.25 times higher interferon-gamma from MO and 1.5 times higher IL
      6 from DFO. By 90min of incubation, MO had 1.11 times higher antigen uptake
      compared to CON, whereas EFO was 0.86 times lower. All fish oil treatments
      resulted in decreasingly mature splenic and bone marrow B-cell subsets. We
      conclude that diets high in n-3 LCPUFAs may elicit similar B-cell phenotypes but
      different organizational and functional outcomes. More specifically, these data
      suggest that the EPA and DHA content of a diet influences immunological outcomes,
      highlighting the importance of understanding how specific n-3 LCPUFAs modulate B
      cell development and function. 

PMID- 25616448
TI  - Multi-antigen print immunoassay (MAPIA)-based evaluation of novel recombinant
      Leishmania infantum antigens for the serodiagnosis of canine visceral
      leishmaniasis.
AB  - BACKGROUND: Domestic dogs are the principal reservoir hosts of Leishmania
      infantum in regions where visceral leishmaniasis (VL) is endemic. Although
      serologic methods are frequently used for the screening of infected dogs,
      antibody-based tests require further assessment, due to lack of sensitivity and
      specificity. In this study, we employed a multi-antigen printing immunoassay
      (MAPIA) to compare the antibody responses to novel recombinant proteins of L.
      infantum with the potential for the detection of canine VL. FINDINGS: MAPIA
      strips were prepared employing 12 recombinant proteins. Antibody reactivity to
      these antigens was compared using a panel of sera collected from clinically
      asymptomatic (n = 16) and symptomatic (n = 41) culture-positive animals. Our
      findings showed that the canine immune response to antigen differs between dogs
      and depends on infection status. Using this screening assay, when five out of the
      12 antigens were combined, an overall 81% detection rate of L. infantum-infected
      dogs was achieved. CONCLUSIONS: We conclude that MAPIA is an effective screening
      tool to rapidly select multiple antigens of diagnostic utility to be used in a
      more sensitive point of care diagnostic test such as the Dual-Path Platform (DPP)
      multiplex test for the rapid detection of infected dogs.

PMID- 25616449
TI  - Factors affecting reorganisation of memory encoding networks in temporal lobe
      epilepsy.
AB  - AIMS: In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation
      in the memory encoding network has been consistently described. Distinct areas of
      reorganisation have been shown to be efficient when associated with successful
      subsequent memory formation or inefficient when not associated with successful
      subsequent memory. We investigated the effect of clinical parameters that
      modulate memory functions: age at onset of epilepsy, epilepsy duration and
      seizure frequency in a large cohort of patients. METHODS: We studied 53 patients
      with unilateral TLE and hippocampal sclerosis (29 left). All participants
      performed a functional magnetic resonance imaging memory encoding paradigm of
      faces and words. A continuous regression analysis was used to investigate the
      effects of age at onset of epilepsy, epilepsy duration and seizure frequency on
      the activation patterns in the memory encoding network. RESULTS: Earlier age at
      onset of epilepsy was associated with left posterior hippocampus activations that
      were involved in successful subsequent memory formation in left hippocampal
      sclerosis patients. No association of age at onset of epilepsy was seen with face
      encoding in right hippocampal sclerosis patients. In both left hippocampal
      sclerosis patients during word encoding and right hippocampal sclerosis patients
      during face encoding, shorter duration of epilepsy and lower seizure frequency
      were associated with medial temporal lobe activations that were involved in
      successful memory formation. Longer epilepsy duration and higher seizure
      frequency were associated with contralateral extra-temporal activations that were
      not associated with successful memory formation. CONCLUSION: Age at onset of
      epilepsy influenced verbal memory encoding in patients with TLE due to
      hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of
      epilepsy and lower seizure frequency were associated with less disruption of the
      efficient memory encoding network whilst longer duration and higher seizure
      frequency were associated with greater, inefficient, extra-temporal
      reorganisation.

PMID- 25616450
TI  - Long-term prognosis of patients with Lennox--Gastaut syndrome in recent decades.
AB  - PURPOSE: We investigated long term prognosis of Lennox-Gastaut syndrome (LGS)
      with active application of recent advanced treatment modalities such as ketogenic
      diet (KD) or epilepsy surgery (ES). METHODS: We retrospectively evaluated 68
      patients with LGS, aged 18-35 years. We assessed seizure outcomes for a range of
      therapeutic modalities. Evolution of seizure types, EEG characteristics,
      cognition, ambulation, social outcomes and other clinical data were also
      evaluated. RESULTS: For a mean follow-up duration of 19.3 years (range 8.3-32.5
      years), finally sixteen patients (23.5%) were seizure-free. Of the 68 patients,
      26 (38.2%) were treated solely with AEDs and six became seizure-free. The KD was
      administered to 19 patients, five patients maintained a seizure free state during
      the KD but only one patient was able to maintain a seizure free state by
      continuing on a modified Atkins diet. Focal resective surgery was performed in 15
      patients, ten out of the 15 patients had Engel class I outcomes, but only three
      patients maintained seizure freedom to adults. CC was performed in 17 patients,
      and VNS was performed in 14 patients. These palliative procedures were also
      effective but had limitations to obtain and maintain seizure freedom to adults.
      Characteristic EEG features of diffuse slow spike-wave and generalized paroxysmal
      fast activity ceased in half of the patients. In cognitive terms, 94.7% of
      patients exhibited moderate to profound mental retardation. Only 39.7% of
      patients had intact independent daily living skills, and 25.4% could not walk,
      even with support. CONCLUSIONS: KD and epilepsy surgery were effective for
      seizure control, but they did not necessarily lead to the maintenance of a
      seizure-free state. LGS remains a form of intractable epilepsy despite the
      application of recent advanced treatment modalities.

PMID- 25616451
TI  - Low brain ascorbic acid increases susceptibility to seizures in mouse models of
      decreased brain ascorbic acid transport and Alzheimer's disease.
AB  - Seizures are a known co-occurring symptom of Alzheimer's disease, and they can
      accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C
      (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to
      present with clinical signs of scurvy (e.g. lethargy, hemorrhage,
      hyperkeratosis), are easily obtainable with insufficient dietary intake, and may
      contribute to the oxidative stress environment of both Alzheimer's disease and
      epilepsy. The purpose of this study was to test whether mice that have diminished
      brain ascorbic acid in addition to carrying human Alzheimer's disease mutations
      in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had
      altered electrical activity in the brain (electroencephalography; EEG), and were
      more susceptible to pharmacologically induced seizures. Brain ascorbic acid was
      decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2
      (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease
      in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with
      ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative
      stress in brain, increased mortality, faster seizure onset latency following
      treatment with kainic acid (10 mg/kg i.p.), and more ictal events following
      pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely
      novel phenomenon that ascorbic acid deficiency alone increased the severity of
      kainic acid- and pentylenetetrazol-induced seizures. These data suggest that
      avoiding ascorbic acid deficiency may be particularly important in populations at
      increased risk for epilepsy and seizures, such as Alzheimer's disease.

PMID- 25616452
TI  - Dynamic preictal relations in FCD type II: potential for early seizure detection
      in focal epilepsy.
AB  - In focal epilepsy, power imbalance between spike-related high frequency
      oscillations (HFOs) with 80-200 Hz and post-spike slow waves (PSS) in the spike
      and slow waves selectively occurs within the seizure onset zone (SOZ) before
      seizure onset. The aim of this study was to elucidate when this preictal power
      imbalance could occur in the SOZ. We analyzed intracranial EEG data from 6
      patients with focal cortical dysplasia. During preictal 3-min period, which was
      divided into three intervals: 0-1 min, 1-2 min 2-3 min before seizure onset, we
      performed correlation (Spearman's coefficient) and simple linear regression
      analyses comparing power of spike-related HFOs and PSS. We analyzed 719 +/- 57
      (mean +/- SD) spike and slow waves per patient, which were obtained from three
      seizures. In the SOZ, the positive correlation between spike-related HFO and PSS
      power was drastically reduced during preictal 3-min period, and the slope of
      regression line (DeltaPSS power/DeltaHFO power) decreased significantly during 0
      1 min before seizure onset (p < 0.05, Steel-Dwass test). The present results
      indicate that the preictal dynamics of HFO and PSS power in the SOZ may have
      utility for early seizure detection.

PMID- 25616453
TI  - Enhanced EEG connectivity in children with febrile seizures.
AB  - BACKGROUND: Epilepsy is currently conceptualized as a disturbance of neuronal
      networks with altered connectivity that persists into the interictal phase.
      Febrile seizures are sometimes a precursor in childhood of lifelong epilepsy. We
      investigated whether studying functional connectivity in children with febrile
      seizures could help understand the mechanisms underlying their long-term seizure
      susceptibility. METHODS: EEG was recorded during rest and intermittent photic
      stimulation (IPS) in 12 FS patients, 5 siblings and 15 control children between 6
      and 36 months of age. Original EEG data were transformed into source space using
      a multiple regional source model. Source coherence values were calculated for the
      interfrontal, interoccipital and occipito-frontal connections for the delta,
      theta, alpha, beta and gamma frequency bands. RESULTS: Our results suggest
      enhanced delta and theta frequency EEG source coherence in patients with FSs
      compared to siblings and control children, both under resting conditions and
      during IPS, more consistent for the theta band and the occipito-frontal
      connections. CONCLUSIONS: Enhanced connectivity in patients with FSs could
      indicate a seizure-prone state and interfere with the maturation of cerebral
      networks. Further prospective studies are needed to assess whether
      hyperconnectivity is a risk factor for epileptogenesis and neurodevelopmental
      disorders.

PMID- 25616454
TI  - Selective medial temporal volume reduction in the hippocampus of patients with
      idiopathic generalized tonic-clonic seizures.
AB  - BACKGROUND: Different subtypes of idiopathic generalized epilepsy may indicate
      different mechanisms and outcomes, suggesting that it is necessary to use a 'pure
      sample' of a single subtype. METHODS: A volumetric study, in conjunction with
      cognition assessments, was performed in a pure sample of patients with idiopathic
      generalized tonic-clonic seizures (IGE-GTCS; 15 males and 15 females) matched
      with normal control subjects (15 males and 17 females). The volumetric
      measurements were focused on the hippocampus and its surrounding structures,
      including the amygdala, the parahippocampal gyrus, the entorhinal cortex and the
      perirhinal cortex. The Wechsler Adult Intelligence Scale-Revised in China was
      administered to assess cognitive status. RESULTS: A volume reduction was found
      only in the hippocampus, with a more severe effect on the left side than the
      right side. The total number and frequency of seizures had significant negative
      correlations with multiple cognitive measures. Furthermore, the hippocampal
      volume reduction was significantly correlated with some aspects of cognitive
      impairment. CONCLUSION: These findings suggest that compared with the other
      medial temporal structures, the hippocampus may be more vulnerable to the
      neuropathology of IGE-GTCS. The observation that cognitive deterioration was
      correlated with an increased frequency and total number of seizures highlights
      the critical importance of preventing seizures from recurrence.

PMID- 25616455
TI  - Relationship between initial electroencephalographic characteristics and seizure
      outcomes in children with non-lesional West syndrome.
AB  - BACKGROUND: To characterize the initial interictal electroencephalography (EEG)
      activities associated with seizure outcomes in children with non-lesional West
      syndrome (WS), and their worth in the prediction of seizure-free (SF) vs no
      seizure-free (No-SF) outcomes. METHODS: We retrospectively reviewed the initial
      scalp EEGs for at least a 40-min duration, and the medical records of 66 children
      who were diagnosed as WS with normal MRI, and who were followed-up with for 4.5
      +/- 2.1 years. We assessed the following clinical and EEG findings: onset of
      seizures, development, underlying etiologies, initial interictal EEGs, and
      seizure evolution. These variables were compared between two groups: SF vs No-SF
      groups. RESULTS: In total, 36 (54.5%) children had SF outcomes and 30 (45.5%) had
      No-SF outcomes during long-term follow-up (4.4 +/- 2.3 vs 4.6 +/- 2.0 years, p =
      0.7644). The mean age at seizure onset was similar in the SF and No-SF groups
      (6.0 +/- 3.0 vs 6.9 +/- 3.2 months, p = 0.2443). Delayed development before the
      onset of spasms was similarly observed in both groups (13.9% vs 13.3%). Initial
      EEG findings significantly differed with typical hypsarrhythmia (41.7% vs 73.3%,
      p = 0.0098), multiple independent spike foci (MISF) (55.6% vs 83.3%, p = 0.0158),
      frontal-dominant MISF (0.0% vs 40.0%, p < 0.0001), and frontal-dominant
      generalized epileptiform discharges (EDs) (0.0% vs 16.7%, p=0.0108) being
      involved more infrequently in the SF group than in the No-SF group, respectively.
      Patients in the SF group showed no frontal-dominant MISF or frontal-dominant
      generalized EDs, and a more often normal to borderline sleep-spindle (83.3% vs
      40.0%, p = 0.0002) than the No-SF group. CONCLUSION: Patients with SF outcomes
      more frequently showed the posterior-dominant generalized EDs and normal to
      borderline sleep-spindle, and the No-SF group more often had typical
      hypsarrhythmia, frontal-dominant MISF, frontal-dominant generalized EDs, and no
      normal sleep-spindle. Initial interictal EEG findings may predict seizure
      outcomes in patients with non-lesional WS.

PMID- 25616456
TI  - Predictors of spontaneous transient seizure remission in patients of medically
      refractory epilepsy due to mesial temporal sclerosis (MTS).
AB  - PURPOSE: To analyze the predictors of spontaneous transient seizure remission for
      >=1 year in patients with drug-resistant epilepsy (DRE) due to mesial temporal
      sclerosis (MTS). METHODS: This analysis included 38 patients with DRE (M:F =
      20:18, age: 31.7 +/- 10.9 years) diagnosed with unilateral MTS (right:left =
      16:22). Group I ('remission' group) comprised of patients with seizure remission
      (M:F = 10:8, age: 32.8 +/- 12.3 years, mean seizure free period: 2.2 +/- 1.1
      years; median: 2.1 years). Group II ('non-remission' group) comprised of age and
      gender matched 20 patients (M:F = 10:10, age: 30.7 +/- 9.7 years) with unilateral
      MTS who never had seizure remission and subsequently underwent epilepsy surgery.
      Groups I and II were compared to find the predictors associated with transient
      seizure remission. RESULTS: The age at onset of seizures in group I was 13.2 +/-
      11.8 years and in group II was 12.0 +/- 7.6 years. The duration of seizure was:
      group I - 19.7 +/- 12.5 years and group II - 19.3 +/- 7.7 years. Past history of
      seizure remissions (p < 0.001), frequent periods of remissions (p < 0.001), first
      remission within a year of onset of seizures (p = 0.04) and normal EEG (p = 0.04)
      were the important clinical predictors associated with seizure remission in this
      cohort. Fifteen patients in group I (83.3%) experienced remission following
      either change in AED (p <= 0.001) or increase in AED dosages (p < 0.001). There
      was no difference between the two groups regarding the type of semiology (partial
      vs. secondarily generalized) (p = 0.50), family history of seizures (p = 1.0),
      side of the lesion (p = 0.34), history of febrile seizures (p = 1.0) and the
      number of AEDs used (p = 0.53). CONCLUSION: The present study unfolds, some of
      the clinically relevant predictors associated with transient seizure remission in
      patients with DRE and MTS. Future molecular and network studies are required to
      understand its mechanism.

PMID- 25616457
TI  - 3T-MRI in patients with pharmacoresistant epilepsy and a vagus nerve stimulator:
      a pilot study.
AB  - PURPOSE: For safe 3T-MRI of patients with VNS (vagus nerve stimulator), specific
      conditions are mandatory. However, application of these conditions can lead to a
      loss of image quality. In this work, we evaluated the diagnostic value of 3T-MRI
      in VNS patients with pharmacoresistant epilepsy. METHODS: Using a transmit-and
      receive head coil and adapting our sequences to allow for low SAR (specific
      absorption rate), we examined 15 patients with pharmacoresistant epilepsy.
      Diagnostic quality was assessed by comparison of the SNR (signal to noise ratio)
      and CNR (contrast to noise ratio) of the hippocampus, the grey-white matter
      contrast and epileptogenic lesions to images of patients without VNS acquired
      with our routine 3T-MRI protocol and the 32-channel head coil. RESULTS: 3T-MRI is
      feasible in VNS-patients. Image quality is adequate for detection and follow-up
      of epileptogenic lesions such as ganglioglioma or PNH (periventricular nodular
      heterotopia). Due to a significant reduction of SNR and CNR, the diagnostic value
      for subtle lesions may be decreased. Overall, the feasibility of 3T-MRI is
      beneficial in the diagnostic workup and follow-up of epilepsy-patients with VNS.

PMID- 25616458
TI  - Long-term outcomes in patients after epilepsy surgery failure.
AB  - PURPOSE: The primary aim of this study was to analyze the long-term outcomes of
      patients who were classified as Engel IV one year after resective epilepsy
      surgery. The secondary objectives were to evaluate the effectiveness of different
      treatment options and to examine the reasons that the patients did not undergo
      resective reoperation. METHODS: Our study was designed as a retrospective open
      label investigation of the long-term outcomes of 34 patients (12% of all
      surgically treated patients) who were classified as Engel IV one year after
      epilepsy surgery. RESULTS: At the last follow-up visit (average of 7.6 +/- 4.2
      years after surgery), 12 of the 34 examined patients (35.3%) were still
      classified as Engel IV; 22 of the 34 patients (64.7%) were improved (Engel I
      III). Of the 34 patients, 8 (23.5%) achieved an excellent outcome, classified as
      Engel I, 3 patients (8.8%) were classified as Engel II, and 11 patients (32.4%)
      as Engel III. The seizure outcome in the patients classified as Engel I was
      achieved by resective reoperation in 4; by a change in antiepileptic medication
      in 3 patients; and by vagus nerve stimulation (VNS) in 1 patient. The seizure
      outcome of Engel II was achieved by a change in antiepileptic medication in all 3
      patients. Of the 34 patients, a total of 6 (17.6%) underwent resective
      reoperation only. The major reasons for this were the absence of a plausible
      hypothesis for invasive re-evaluation, the risk of postoperative deficit, and
      multifocal epilepsy in the rest of patients. CONCLUSION: Although the reoperation
      rate was relatively low in our series, we can achieve better or even excellent
      seizure outcomes using other procedures in patients for whom resective surgery
      initially failed.

PMID- 25616459
TI  - Electrocorticographic language mapping in children by high-gamma synchronization
      during spontaneous conversation: comparison with conventional electrical cortical
      stimulation.
AB  - INTRODUCTION: This study describes development of a novel language mapping
      approach using high-gamma modulation in electrocorticograph (ECoG) during
      spontaneous conversation, and its comparison with electrical cortical stimulation
      (ECS) in childhood-onset drug-resistant epilepsy. METHODS: Patients undergoing
      invasive pre-surgical monitoring and able to converse with the investigator were
      eligible. ECoG signals and synchronized audio were acquired during quiet baseline
      and during natural conversation between investigator and the patient. Using
      Signal Modeling for Real-time Identification and Event Detection (SIGFRIED)
      procedure, a statistical model for baseline high-gamma (70-116 Hz) power, and a
      single score for each channel representing the probability that the power
      features in the experimental signal window belonged to the baseline model, were
      calculated. Electrodes with significant high-gamma responses (HGS) were plotted
      on the 3D cortical model. Sensitivity, specificity, positive and negative
      predictive values (PPV, NPV), and classification accuracy were calculated
      compared to ECS. RESULTS: Seven patients were included (4 males, mean age 10.28
      +/- 4.07 years). Significant high-gamma responses were observed in classic
      language areas in the left hemisphere plus in some homologous right hemispheric
      areas. Compared with clinical standard ECS mapping, the sensitivity and
      specificity of HGS mapping was 88.89% and 63.64%, respectively, and PPV and NPV
      were 35.29% and 96.25%, with an overall accuracy of 68.24%. HGS mapping was able
      to correctly determine all ECS+ sites in 6 of 7 patients and all false-sites
      (ECS+, HGS- for visual naming, n = 3) were attributable to only 1 patient.
      CONCLUSIONS: This study supports the feasibility of language mapping with ECoG
      HGS during spontaneous conversation, and its accuracy compared to traditional
      ECS. Given long-standing concerns about ecological validity of ECS mapping of
      cued language tasks, and difficulties encountered with its use in children, ECoG
      mapping of spontaneous language may provide a valid alternative for clinical use.

PMID- 25616460
TI  - Standard dose valproic acid does not cause additional cognitive impact in a
      rodent model of intractable epilepsy.
AB  - Children with epilepsy face significant cognitive and behavioral impairments.
      These impairments are due to a poorly characterized interaction between the
      underlying etiology, the effect of seizures and the effect of medication. The
      large variation in these factors make understanding the main drivers of cognitive
      impairment in humans extremely difficult. Therefore, we investigated the
      cognitive effect of seizures and the antiepileptic drug valproic acid in a rodent
      model of cortical dysplasia. Rats were divided into seizure-receiving and non
      receiving groups. Rats experienced frequent early life seizures using the
      flurothyl inhalation method: 50 seizures between postnatal day 5 and 15 and then
      one seizure a day following that. Rats were further divided into drug-treated and
      vehicle treated groups. Valproic acid treated animals were treated from 5 days
      preceding behavioral testing in the Morris water maze at a clinically relevant
      concentration. We show here that the main driver of cognitive impairments are the
      brain malformations, and that persistent seizures in animals with brain
      malformations and valproic acid caused no additional impact. These findings
      suggest that neither an appropriate dose of a standard antiepileptic drug or
      intractable seizures worsen cognition associated with a malformation of cortical
      development and that alternative treatment strategies to improve cognition are
      required. 

PMID- 25616461
TI  - Diffusion tensor imaging tractography of Meyer's loop in planning resective
      surgery for drug-resistant temporal lobe epilepsy.
AB  - PURPOSE: Whether Meyer's loop (ML) tracking using diffusion tensor imaging
      tractography (DTIT) can be utilized to avoid post-operative visual field deficits
      (VFD) after anterior temporal lobectomy (ATL) for drug-resistant temporal lobe
      epilepsy (TLE) using a large cohort of controls and patients. Also, we wanted to
      create a normative atlas of ML in normal population. METHODS: DTIT was used to
      study ML in 75 healthy subjects and 25 patients with and without VFD following
      ATL. 1.5T MRI echo-planar DTI sequences with DTI data were processed in Nordic
      ICE using a probabilistic method; a multiple region of interest technique was
      used for reconstruction of optic radiation trajectory. Visual fields were
      assessed in patients pre- and post-operatively. RESULTS: Results of ANOVA showed
      that the left ML-TP distance was less than right across all groups (p = 0.01).
      The average distance of ML from left temporal pole was 37.44 +/- 4.7 mm (range:
      32.2-46.6 mm) and from right temporal pole 39.08 +/- 4.9 mm (range: 34.3-49.7
      mm). Average distance of left and right temporal pole to tip of temporal horn was
      28.32 +/- 2.03 mm (range: 26.4-32.8 mm) and was 28.92 +/- 2.09 mm, respectively
      (range: 25.9-33.3 mm). If the anterior limit of the Meyer's loop was <=38 mm on
      the right and <=35 mm on the left from the temporal pole, they are at a greater
      risk of developing VFDs. CONCLUSIONS: DTIT is a novel technique to delineate ML
      and plays an important role in planning surgical resection in TLE to predict post
      operative visual performance and disability.

PMID- 25616462
TI  - Effect of caffeine and adenosine receptor ligands on the expression of spike-and
      wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS).
AB  - The influence of caffeine on epileptic seizures remains a matter of debate. Here
      we tested on Genetic Absence Epilepsy Rats from Strasbourg (GAERS) the
      consequences of acute and chronic exposure to caffeine on the expression of spike
      and-wave discharges (SWDs). Since caffeine is a mixed nonspecific A(1) and A(2A)
      adenosine receptor antagonist, we measured also the influence of antagonists and
      agonists of these receptors on SWD expression. GAERS were equipped with four
      cortical electrodes over the frontoparietal cortex and the cumulated duration and
      number of SWDs were recorded for 120 min after the injection of increasing doses
      of caffeine, specific antagonists and agonists of A(1) and A(2A) adenosine
      receptors. The effects of chronic caffeine were also studied. In GAERS, caffeine
      dose-dependently reduced the cumulated number and duration of SWDs which almost
      disappeared after the injection of the two highest doses of caffeine, 5 and 10
      mg/kg. Likewise, the A(1) and A(2A) adenosine receptor antagonists led to a dose
      dependent reduction of SWD expression while the agonists dose-dependently
      increased SWD expression. Conversely, the chronic exposure to caffeine via
      drinking water for 15 days did not influence SWD expression. With the exception
      of the two highest doses of caffeine that largely enhanced activity, all
      compounds including low doses of caffeine had no effect on locomotor activity of
      GAERS. These data show that the acute exposure to low doses of caffeine, or A(1)
      and A(2A) adenosine receptor antagonists reduces SWD expression in GAERS,
      independently from any effect on motor activity. The chronic exposure of GAERS to
      caffeine does not affect the expression of epilepsy.

PMID- 25616463
TI  - The effects of lacosamide on depression and anxiety in patients with epilepsy.
AB  - Depression and anxiety are common in patients with epilepsy. Moreover, some
      antiepileptic drugs (AEDs) have mood stabilizing and anxiolytic effects, while
      others may worsen psychiatric symptoms. The effects of lacosamide, a third
      generation AED approved for the treatment of focal onset seizures, on depressive
      and anxiety symptoms are unknown. We evaluated changes in depression and anxiety
      following the initiation of lacosamide. We compared patients' scores on the
      Neurological Disorders Depression Inventory for Epilepsy (NDDI-E, n = 91) and
      Generalized Anxiety Disorder 7-item (GAD-7, n = 20) scales prior to and following
      lacosamide treatment. Following the initiation of lacosamide, there were no
      significant changes in NDDI-E scores when all patients were analyzed aggregately
      (baseline: 12.14 +/- 4.64 vs post-treatment: 11.91 +/- 4.14, p = 0.51).
      Similarly, the mean GAD-7 scores at baseline (4.10 +/- 4.52) and after treatment
      (4.75 +/- 5.51) did not differ (p = 0.23). In the 25 patients with initial NDDI-E
      scores of >15, lacosamide was associated with a significant decrease in
      depressive symptoms (baseline: 17.60 +/- 1.63 vs post-treatment: 14.64 +/- 2.78,
      p < 0.001). NDDI-E and GAD-7 scores pre- and post-lacosamide initiation were not
      significantly affected by a history of mood disorders, concomitant psychiatric
      medications, or concomitant AEDs with mood-stabilizing effects.

PMID- 25616464
TI  - Cost-effectiveness of the ketogenic diet and vagus nerve stimulation for the
      treatment of children with intractable epilepsy.
AB  - PURPOSE: The objective of this study was to estimate the expected cost-utility
      and cost-effectiveness of the ketogenic diet (KD), vague nerve stimulation (VNS)
      and care as usual (CAU), using a decision analytic model with a 5-year time
      horizon. METHODS: A Markov decision analytical model was constructed to estimate
      the incremental costs, quality-adjusted life years (QALYs) and successfully
      treated patient (i.e. 50% or more seizure reduction) of the treatment strategies
      KD, VNS and CAU, from a health care perspective. The base case considered
      children with intractable epilepsy (i.e. two or more antiepileptic drugs had
      failed) aged between 1 and 18 years. Data were derived from literature and expert
      meetings. Deterministic and probabilistic sensitivity analyses were performed.
      RESULTS: Our results suggest that KD is more effective and less costly, and thus
      cost-effective compared with VNS, after 12 months. However, compared to CAU,
      neither KD nor VNS are cost-effective options, they are both more effective but
      also more expensive (?346,899 and ?641,068 per QALY, respectively). At 5 years,
      VNS is cost-effective compared with KD and CAU (?11,378 and ?68,489 per QALY,
      respectively) and has a 51% probability of being cost-effective at a ceiling
      ratio of ?80,000 per QALY. CONCLUSIONS: Our results suggest that on average the
      benefits of KD and VNS fail to outweigh the costs of the therapies. However,
      these treatment options should not be ignored in the treatment for intractable
      epilepsy in individual or specific groups of patients. There is a great need for
      high quality comparative studies with large patient samples which allow for
      subgroup analyses, long-term follow-up periods and outcome measures that measure
      effects beyond seizure frequency (e.g. quality of life). When this new evidence
      becomes available, reassessment of the cost-effectiveness of KD and VNS in
      children with intractable epilepsy should be carried out.

PMID- 25616465
TI  - Autosomal dominant lateral temporal epilepsy (ADLTE): novel structural and single
      nucleotide LGI1 mutations in families with predominant visual auras.
AB  - PURPOSE: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal
      epilepsy syndrome characterized by prominent auditory or aphasic symptoms.
      Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the
      impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic
      lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE
      patients. METHODS: Twenty-four ADLTE families and 140 sporadic LTE patients with
      no evidence of point mutations in LGI1 were screened for copy number alterations
      using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained
      familial and sporadic LTE patients were clinically investigated, and interictal
      EEG and MRI findings were obtained; probands were tested for LGI1 mutations by
      direct exon sequencing or denaturing high performance liquid chromatography.
      RESULTS: We identified a novel microdeletion spanning LGI1 exon 2 in a family
      with two affected members, both presenting focal seizures with visual symptoms.
      Also, we identified a novel LGI1 missense mutation (c.1118T > C; p.L373S) in a
      newly ascertained family with focal seizures with prominent visual auras, and
      another missense mutation (c.856T > C; p.C286R) in a sporadic patient with
      auditory seizures. CONCLUSIONS: We describe two novel ADLTE families with
      predominant visual auras segregating pathogenic LGI1 mutations. These findings
      support the notion that, in addition to auditory symptoms, other types of auras
      can be found in patients carrying LGI1 mutations. The identification of a novel
      microdeletion in LGI1, the second so far identified, suggests that LGI1
      microrearrangements may not be exceptional.

PMID- 25616466
TI  - An analysis of epileptic negative myoclonus by magnetoencephalography.
AB  - PURPOSE: To clarify the neurophysiologic mechanism of epileptic negative
      myoclonus (ENM), we analyzed the magnetoencephalography (MEG) of a patient with
      ENM. METHODS: The 52-year-old right-handed male had frequent ENM in the right
      upper limb during awake and monthly seizures with sudden tonic stiffening of the
      right forearm during sleep. MRI demonstrated a focal cortical dysplasia in the
      cortex of the posterior portion of the left superior frontal sulcus. Whole-head
      type MEG, electroencephalography and electromyography were simultaneously
      recorded during ENM. Single equivalent currents dipoles (ECDs) were calculated
      for each spike component followed by silent period (SP) in the right deltoid
      muscle. These MEG spike components were averaged with respect to their peaks, and
      single ECD was also calculated for the averaged spike component. Furthermore, we
      analyzed the MEG with the silent-period-locked-averaging (SPLA) method. Twenty
      MEG signal data were averaged with respect to the onset of SP. Twenty epochs in
      each of five separate periods of recording were repeatedly averaged. ECDs were
      calculated for spike components observed in each averaged epoch. RESULTS: ECDs of
      each spike followed by SP were clustered near the cortex of the left central
      sulcus. In MEG spike averaging and SPLA method, ECDs at the peak of spike
      components were located near the right shoulder division of the primary
      sensorimotor cortex reproducibly. ECDs on the ascending phase before the peak
      were located lateral to the above ECD location in MEG spike averaging method.
      CONCLUSIONS: ENM was produced by an inhibitory action on the primary sensorimotor
      cortex corresponding to the body segment in which ENM occurs.

PMID- 25616467
TI  - Burden of epilepsy: a prevalence-based cost of illness study of direct, indirect
      and intangible costs for epilepsy.
AB  - OBJECTIVES: We aimed to gauge the burden of epilepsy in China from a societal
      perspective by estimating the direct, indirect and intangible costs. METHODS:
      Patients with epilepsy and controls were enrolled from two tertiary hospitals in
      China. Patients were asked to complete a Cost-of-Illness (COI), Willingness-to
      Pay (WTP) questionnaires, two utility elicitation instruments and Mini Mental
      State Examination (MMSE). Healthy controls only completed WTP questionnaire, and
      utility instruments. Univariate analyses were performed to investigate the
      differences in cost on the basis of different variables, while multivariate
      analysis was undertaken to explore the predictors of cost/cost component.
      RESULTS: In total, 141 epilepsy patients and 323 healthy controls were recruited.
      The median total cost, direct cost and indirect cost due to epilepsy were
      US$949.29, 501.34 and 276.72, respectively. Particularly, cost of anti-epileptic
      drugs (AEDs) (US$394.53) followed by cost of investigations (US$59.34), cost of
      inpatient and outpatient care (US$9.62) accounted for the majority of the direct
      medical costs. While patients' (US$103.77) and caregivers' productivity costs
      (US$103.77) constituted the major component of indirect cost. The intangible
      costs in terms of WTP value (US$266.07 vs. 88.22) and utility (EQ-5D, 0.828 vs.
      0.923; QWB-SA, 0.657 vs. 0.802) were both substantially higher compared to the
      healthy subjects. CONCLUSIONS: Epilepsy is a cost intensive disease in China.
      According to the prognostic groups, drug-resistant epilepsy generated the highest
      total cost whereas patients in seizure remission had the lowest cost. AED is the
      most costly component of direct medical cost probably due to 83% of patients
      being treated by new generation of AEDs.

PMID- 25616468
TI  - Prevalence of depressive symptoms and their impact on quality of life in patients
      with drug-resistant focal epilepsy (IMDYVA study).
AB  - BACKGROUND: Drug-resistant epilepsy (DRE) is usually related to focal epilepsy
      (FE) and is present in up to 30% of patients. Several studies have found high
      rates of depressive symptoms and poor health related quality of life (HRQOL) in
      DRE patients but little information is available on these aspects for Spain.
      OBJECTIVE: To determine the prevalence of depressive symptoms in a cohort of
      Spanish patients with DRE and evaluate their HRQOL in comparison with patients
      with controlled FE (CFE). METHODS: This observational cross-sectional study
      analyzed FE patients, with and without DRE, recruited from different Spanish
      neurology outpatient clinics. Presence of depressive symptoms was assessed using
      the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression
      Inventory-II (BDI-II). HRQOL was evaluated using the Quality of Life in Epilepsy
      Inventory (QOLIE-31). RESULTS: 515 patients (DRE = 248) were included. Mean (SD)
      age was 44.3 (15.4) years and 50.5% were male. Overall, 15.9% had a previous
      diagnosis of depressive symptoms (DRE = 22.6%; CFE = 9.7%, p < 0.001). Depressive
      symptoms was observed in 62.1% [95% CI 56.1-68.1] and 64.8% [58.8-70.7] of DRE
      patients using MADRS and BDI-II, respectively, compared to 32.6% [27.0-38.2] and
      37.2% [31.4-43.0] in the CFE group (p < 0.001). Depressive symptoms was
      associated with poorer HRQOL. Multivariate modeling showed that presence of
      depressive symptoms on the MADRS or BDI-II had the greatest impact on mean QOLIE
      31 scores. CONCLUSIONS: Compared to other studies, the rate of depressive
      symptoms was high (60% in DRE and 30% in CFE patients). MADRS and BDI-II showed a
      positive correlation. Prior to the study, depressive symptoms were underdiagnosed
      in a large proportion of patients. Clinical diagnosis of depressive symptoms and
      not seizure frequency was associated with poorer mean QOLIE-31 scores.

PMID- 25616469
TI  - Status epilepticus results in region-specific alterations in seizure
      susceptibility along the hippocampal longitudinal axis.
AB  - Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome in adults. In
      particular, the hippocampus is highly susceptible to abnormal synchronization.
      Recent advances in the surgical treatment of patients with refractory TLE have
      shown that multiple hippocampal transections can effectively control seizures. It
      has been suggested that in TLE the synchrony in the longitudinal connections is
      required for seizure generation; however the physiological background for the
      increase in hippocampal synchronization along the longitudinal axis is not fully
      understood. The hippocampus varies in seizure susceptibility along its
      longitudinal axis with the ventral hippocampus (VH) region being more seizure
      prone and susceptible to neuronal damage than the dorsal hippocampus (DH). In the
      present study we studied seizure susceptibility along the longitudinal axis of
      the hippocampus following pilocarpine-induced status epilepticus (SE). In control
      conditions the VH generates epileptiform activity (EA) more frequently than the
      DH when exposed to a low Mg(2+)/1Ca(2+)/5K(+) solution. Following SE the
      probability of inducing epileptiform activity (EA) is similar in the VH and DH
      slices. This SE-induced change is due to an increase in the proportion of DH
      slices responding to the low Mg(2+)/1Ca(2+)/5K(+) solution with EA. Moreover,
      both the VH and DH show similar responses to a low Mg(2+)/1Ca(2+)/5K(+) solution.
      These findings indicate that the hippocampus undergoes significant functional
      changes following SE, which may provide the necessary increase of synchrony along
      the longitudinal axis to generate seizures in TLE. 

PMID- 25616471
TI  - Predictors of functional disability at hospital discharge after status
      epilepticus.
AB  - OBJECTIVE: Although status epilepticus is a common neurological emergency,
      literature about its short term functional disability is scarce and often
      difficult to interpret. The aim of the present study was to identify possible
      predictive factors of functional disability in a well-selected cohort of EEG
      confirmed status epilepticus patients. METHODS: We carried out a retrospective
      evaluation of clinical and radiologic parameters potentially affecting status
      epilepticus-related disability in a cohort of adult patients admitted to our
      institution between 2003 and 2013. Functional decline was defined as a >= 1
      increase in the modified Rankin scale from preadmission to discharge. RESULTS:
      Seventy-nine patients fulfilled inclusion criteria (46% male). Median age was 69
      years. History of epilepsy was present in 49% of patients. Deterioration occurred
      in 46 subjects (58%). Multivariate analysis revealed the following negative
      predicting factors for disability: normal neuroimaging (OR = 0.031) and presence
      of status epilepticus on hospital admission (OR = 0.127). SIGNIFICANCE: Patients
      without evident brain lesions are at low risk of functional deterioration
      development. SE on admission portends a good prognosis as well, probably because
      it is more promptly treated and it develops in subjects with less systemic
      complications compared to those in hospital.

PMID- 25616470
TI  - Increasing structural atrophy and functional isolation of the temporal lobe with
      duration of disease in temporal lobe epilepsy.
AB  - BACKGROUND: Due to pharmacoresistant seizures and the underutilization of
      surgical treatments, a large number of temporal lobe epilepsy (TLE) patients
      experience seizures for years or decades. The goal of this study was to generate
      a predictive model of duration of disease with the least number of parameters
      possible in order to identify and quantify the significant volumetric and
      functional indicators of TLE progression. METHODS: Two cohorts of subjects
      including 12 left TLE, 21 right TLE and 20 healthy controls (duration = 0) were
      imaged on a 3T MRI scanner using high resolution T1-weighted structural MRI and
      20 min of resting functional MRI scanning. Multivariate linear regression methods
      were used to compute a predictive model of duration of disease using 49
      predictors including functional connectivity and gray matter volumes computed
      from these images. RESULTS: No model developed from the full set of data
      accurately predicted the duration of disease across the entire range from 3 to 50
      years. We then performed the regression on 35 subjects with durations of disease
      in the range 10 to 35 years. The resulting predictive model showed that longer
      durations were associated with reductions in functional connectivity from the
      ipsilateral temporal lobe to the contralateral temporal lobe, precuneus and mid
      cingulate, and with decreases in volume of the ipsilateral hippocampus and
      pallidum. CONCLUSIONS: Functional and volumetric parameters accurately predicted
      duration of disease in TLE. The findings suggest that TLE is associated with a
      gradual functional isolation and significant progressive structural atrophy of
      the ipsilateral temporal lobe over years of duration in the range of 10-35 years.
      Furthermore, these changes can also be detected in the contralateral hemisphere
      in these patients, but to a lesser degree.

PMID- 25616472
TI  - Impact of epilepsy surgery on the quality of life of a low-income population
      through the application of the Qolie-10 scale.
AB  - OBJECTIVE: To describe the impact of epilepsy surgery on quality of life through
      the application of the quality of life in epilepsy (QOLIE-10) scale in a low
      income population. METHODS: We conducted an observational, descriptive, and cross
      sectional study. The data for all patients who underwent epilepsy surgery from
      the aforementioned period were registered retrospectively through a review of
      their clinical history. Clinical variables of interest for this study were
      obtained through phone contact, and the QOLIE-10 scale was applied. RESULTS: This
      study included a total of 89 patients with whom phone contact was established and
      who met the inclusion criteria. Of these patients, 30.3% were without anti
      seizure medication at the time of the survey's application, and only 19.1% were
      still under polytherapy. A total of 47.1% of the patients had returned to some
      work activity that they would have not been able to perform before because of
      their disease. All of the components of the QOLIE-10 scale improved significantly
      (p < 0.05) after the surgical procedure, except the variable of "fear of the
      sudden occurrence of seizures". The variables with greatest impact after the
      surgical procedure were depression, work activity, and quality of life in
      general. CONCLUSION: Epilepsy surgery has a positive impact on the quality of
      life of patients with low resources and in vulnerable social conditions. It is
      still to be determined if, in this population, work and social reintegration have
      a greater impact on the quality of life than other clinical and/or paraclinical
      variables.

PMID- 25616473
TI  - Current understanding of the mechanism of action of the antiepileptic drug
      lacosamide.
AB  - The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3
      methoxypropanamide], a chiral functionalized amino acid, was originally
      identified by virtue of activity in the mouse and rat maximal electroshock (MES)
      test. Attention was drawn to lacosamide because of its high oral potency and
      stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but
      inactive against clonic seizures in rodents induced by subcutaneous
      pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic
      models of absence epilepsy. At doses greater than those required to confer
      protection in the MES test, lacosamide inhibits behavioral and electrographic
      seizures in hippocampal kindled rats. It also effectively terminates seizures in
      the rat perforant path stimulation status epilepticus model when administered
      early after the onset of seizures. Lacosamide does not exhibit antiepileptogenic
      effects in kindling or post-status epilepticus models. The profile of lacosamide
      in animal seizure and epilepsy models is similar to that of sodium channel
      blocking antiepileptic drugs, such as phenytoin and carbamazepine. However,
      unlike these agents, lacosamide does not affect sustained repetitive firing (SRF)
      on a time scale of hundreds of milliseconds or affect fast inactivation of
      voltage-gated sodium channels; however, it terminates SRF on a time scale of
      seconds by an apparent effect on sodium channel slow inactivation. Lacosamide
      shifts the slow inactivation curve to more hyperpolarized potentials and enhances
      the maximal fraction of channels that are in the slow inactivated state.
      Currently, lacosamide is the only known antiepileptic drug in clinical practice
      that exerts its anticonvulsant activity predominantly by selectively enhancing
      slow sodium channel inactivation.

PMID- 25616474
TI  - Topography of brain glucose hypometabolism and epileptic network in glucose
      transporter 1 deficiency.
AB  - RATIONALE: (18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET)
      facilitates examination of glucose metabolism. Previously, we described regional
      cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose
      transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in
      Glut1 DS using quantitative image analysis to identify the epileptic network
      based on the regional distribution of glucose hypometabolism. METHODS: (18)F FDG
      PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using
      Statistical parametric Mapping (SPM). Summed images were preprocessed for
      statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest
      (ROI) analysis was performed to validate SPM results. RESULTS: Visual analysis of
      the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism
      in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison
      using SPM analysis confirmed that the regional distribution of glucose hypo
      metabolism was present in thalamus, cerebellum, temporal cortex and central
      lobule. Two mildly affected patients without epilepsy had hypometabolism in
      cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose
      hypometabolism did not correlate with age at the time of PET imaging, head
      circumference, CSF glucose concentration at the time of diagnosis, RBC glucose
      uptake, or CNS score. CONCLUSION: Quantitative analysis of (18)F FDG-PET imaging
      in Glut1 DS patients confirmed that hypometabolism was present symmetrically in
      thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus
      correlated with the clinical history of epilepsy.

PMID- 25616475
TI  - Efficacy and safety of perampanel in the subgroup of elderly patients included in
      the phase III epilepsy clinical trials.
AB  - Clinical data regarding use of antiepileptic drugs in the elderly are generally
      scarce. Therefore, a subanalysis of subjects aged >= 65 years who participated in
      the 3 phase III perampanel studies was undertaken to determine efficacy and
      safety in these patients. Efficacy (change in seizure frequency/28 days and 50%
      responder rate) in the elderly subgroup was found to be consistent with the adult
      population. Adverse event rates were also largely similar, with some exceptions.
      Because risks of falls, dizziness, and fatigue were greater in the elderly,
      careful titration of perampanel in patients aged >= 65 years is suggested,
      especially at higher doses, where balancing tolerability and clinical response is
      necessary.

PMID- 25616476
TI  - Hyperventilation induces sympathetic overactivation in mesial temporal epilepsy.
AB  - OBJECTIVE: Hyperventilation (HV) during electroencephalography (EEG) is a
      standard clinical procedure to trigger seizures in patients affected by mesial
      temporal lobe epilepsy (MTLE). Despite the pathophysiology of this susceptibility
      to HV is not definitively understood, it may be hypothesized to be related to
      ictal and interictal sympathetic nervous system abnormalities, the presence of
      which is well known in MTLE patients. In order to test this hypothesis we
      investigated the HV effect on heart rate variability (HRV) in a group of MTLE
      patients, compared to a matched group of healthy controls. MATERIAL AND METHODS:
      Forty patients affected by MTLE and 40 age- and sex-matched controls were
      enrolled in the study. In those subjects, a standard electroencephalographic
      recording has been acquired and the high and the low frequency components (HF,
      LF) of heart rate variability (HRV) and their ratio (LF/HF) have been analyzed at
      rest and during the HV. Indeed, LF/HF is a reliable index of sympathetic tone
      modulation. RESULTS: HRV did not differ between MTLE and healthy subjects at
      rest, whereas HV induced a significant LF/HF increase only in MTLE. Within the
      MTLE group, males showed higher LF/HF increase during HV respect to females,
      while no differences related to the side of the epileptic focus were found.
      DISCUSSION: MTLE patients showed an increased sympathetic response to HV compared
      to healthy subjects. HRV analysis points towards an autonomic overactivation as a
      pathophysiological pathway subtending seizure triggered by hyperventilation in
      MTLE. Autonomic susceptibility in MTLE may help to explain the increased
      prevalence of arrhythmic events in these patients, potentially predisposing to
      Sudden Unexpected Death in Epilepsy (SUDEP).

PMID- 25616477
TI  - Experienced and anticipated discrimination among people with major depressive
      disorder in Serbia.
AB  - BACKGROUND: Experiences of discrimination have significant impact on the lives of
      people with mental illness. AIM: This study investigates the nature and severity
      of experienced and anticipated discrimination reported by persons with a
      depressive disorder in Serbia. METHODS: Patients were recruited from two
      psychiatric day hospitals and a primary mental health service with a diagnosis of
      major depressive disorder. Interviews were conducted using a socio-demographic
      questionnaire and the Discrimination and Stigma Scale. RESULTS: The respondents
      experienced discrimination mostly in the field of family relationships, making
      and keeping friends and keeping a job. In domains of making close personal
      relationships or applying for education, anticipated discrimination was higher
      than experienced. The need to conceal mental health problems was stronger than
      experiences of being avoided. The need to hide mental health problems was higher
      than the overall score for experienced discrimination. Participants who were
      hospitalized in some period of life reported higher experienced discrimination.
      Compared to younger participants, older participants experienced more negative as
      well as positive discrimination. Married participants experienced more negative
      discrimination than unmarried. CONCLUSION: It is important to design
      interventions to overcome discrimination toward persons with depression at all
      levels.

PMID- 25616478
TI  - Measles outbreak linked to Disney theme parks reaches five states and Mexico.

PMID- 25616479
TI  - Bayesian regression models for the estimation of net cost of disease using
      aggregate data.
AB  - Estimation of net costs attributed to a disease or other health condition is very
      important for health economists and policy makers. Skewness and
      heteroscedasticity are well-known characteristics for cost data, making linear
      models generally inappropriate and dictating the use of other types of models,
      such as gamma regression. Additional hurdles emerge when individual level data
      are not available. In this paper, we consider the latter case were data are only
      available at the aggregate level, containing means and standard deviations for
      different strata defined by a number of demographic and clinical factors. We
      summarize a number of methods that can be used for this estimation, and we
      propose a Bayesian approach that utilizes the sample stratum specific standard
      deviations as stochastic. We investigate the performance of two linear mixed
      models, comparing them with two proposed gamma regression mixed models, to
      analyze simulated data generated by gamma and log-normal distributions. Our
      proposed Bayesian approach seems to have significant advantages for net cost
      estimation when only aggregate data are available. The implemented gamma models
      do not seem to offer the expected benefits over the linear models; however,
      further investigation and refinement is needed.

PMID- 25616480
TI  - Investigation of leptomeningeal enhancement in MS: a postcontrast FLAIR MRI
      study.
AB  - OBJECTIVE: To investigate possible leptomeningeal contrast enhancement using
      postcontrast fluid-attenuated inversion recovery (FLAIR) MRI as an additional
      marker of inflammation in patients with multiple sclerosis (MS). METHODS: A
      cohort of 112 patients (73 women) with clinically definitive MS or a clinically
      isolated syndrome suggestive of CNS demyelination were included. A pathologic
      control group of 5 stroke patients was also examined. MRI was performed on a 3T
      system including FLAIR, T2-weighted, T1-weighted-contrast injection, followed by
      T1-weighted and FLAIR. RESULTS: Of the 112 patients, 39 had an acute relapse at
      the time of MRI. In total, 96 contrast-enhancing lesions were identified on
      postcontrast T1-weighted images. The pathologic control group demonstrated the
      sensitivity of postcontrast FLAIR images demonstrating leptomeningeal enhancement
      in all cases. In contrast, only 1 out of 112 examined patients with MS showed a
      single area of abnormal leptomeningeal contrast enhancement. CONCLUSIONS: In
      contrast to intraparenchymal blood-brain barrier (BBB) dysfunction that is
      frequently seen in patients with MS, BBB dysfunction of leptomeningeal vessels is
      usually not detectable in patients with early MS.

PMID- 25616481
TI  - Can leptomeningeal enhancement be linked to multiple sclerosis?

PMID- 25616482
TI  - Paradoxes in thalamic function and cognition in people with multiple sclerosis:
      less is more.

PMID- 25616483
TI  - Thalamus structure and function determine severity of cognitive impairment in
      multiple sclerosis.
AB  - OBJECTIVE: This study investigates whether changes in functional connectivity,
      diffusivity, and volume of the thalamus can explain different severities of
      cognitive impairment in multiple sclerosis (MS). METHODS: An inception cohort of
      157 patients with MS (104 women, mean age 41 years), 6 years postdiagnosis, was
      divided into 3 groups: cognitively preserved (CP, n = 108), mildly cognitively
      impaired (MCI, n = 22), and more severely cognitively impaired (SCI, n = 27).
      These groups were matched to 47 healthy controls (HC, 28 women, mean age 41
      years). Thalamic volume, thalamic skeleton diffusivity (fractional anisotropy
      [FA] and mean diffusivity [MD]), and thalamic resting-state functional
      connectivity (FC) were compared between groups. RESULTS: Thalamic volume was
      significantly lower in all patient groups compared to controls, with lowest
      volumes in patients with SCI, and no difference between CP and MCI. Thalamic
      skeleton FA was decreased in SCI compared to HC only; MD was increased in SCI
      compared to all other groups. Thalamic FC was increased in SCI with a total of 15
      regions, mainly sensorimotor, frontal, and occipital parts of the brain. Thalamic
      volume, FC, and MD remained independent predictors in a linear regression model
      (R(2) = 0.46), together with male sex and a lower level of education. Lesion and
      whole-brain volumes were not significant predictors. CONCLUSIONS: These findings
      indicate that thalamic changes in structure and function are highly informative
      regarding overall cognitive performance in MS. Increased thalamic FC only became
      apparent in SCI, possibly as a sign of maladaption.

PMID- 25616484
TI  - Stimulating the brain for epilepsy.

PMID- 25616485
TI  - Long-term treatment with responsive brain stimulation in adults with refractory
      partial seizures.
AB  - OBJECTIVE: The long-term efficacy and safety of responsive direct
      neurostimulation was assessed in adults with medically refractory partial onset
      seizures. METHODS: All participants were treated with a cranially implanted
      responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via
      chronically implanted electrodes when specific electrocorticographic patterns are
      detected (RNS System). Participants had completed a 2-year primarily open-label
      safety study (n = 65) or a 2-year randomized blinded controlled safety and
      efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year
      study to assess safety and efficacy. RESULTS: The average participant was 34 (+/
      11.4) years old with epilepsy for 19.6 (+/-11.4) years. The median preimplant
      frequency of disabling partial or generalized tonic-clonic seizures was 10.2
      seizures a month. The median percent seizure reduction in the randomized blinded
      controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized
      estimating equation) and ranged from 48% to 66% over postimplant years 3 through
      6 in the long-term study. Improvements in quality of life were maintained (p <
      0.05). The most common serious device-related adverse events over the mean 5.4
      years of follow-up were implant site infection (9.0%) involving soft tissue and
      neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first
      direct brain responsive neurostimulator. Acute and sustained efficacy and safety
      were demonstrated in adults with medically refractory partial onset seizures
      arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience
      supports the RNS System as a treatment option for refractory partial seizures.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults
      with medically refractory partial onset seizures, responsive direct cortical
      stimulation reduces seizures and improves quality of life over a mean follow-up
      of 5.4 years.

PMID- 25616488
TI  - Clinical Relevance of matrix metalloproteinase 9 in patients with acute coronary
      syndrome.
AB  - We measured levels of matrix metalloproteinase 9 (MMP-9) as a potential risk
      factor in 75 patients with acute coronary syndrome (ACS) compared to 25 patients
      with stable angina (SA) and 20 healthy participants. Patients were studied
      stressing on smoking, hypertension, diabetes, lipid profile, cardiac enzymes, MMP
      9, and electrocardiography. Patients with ACS had higher MMP-9 levels than the SA
      group. The highest MMP-9 levels were found among ST-elevated myocardial
      infarction (MI), while the lowest levels were found among the control group. The
      MMP-9 level was significantly higher among patients with ACS having poor disease
      outcome (recurrent ischemic attacks, congestive heart failure, or death). The MMP
      9 cutoff value of 3100 pg/mL was able to discriminate MI from unstable angina
      (UA), while the best prognostic utility was established at 4700 pg/mL. We suggest
      that serum MMP-9 could be an early marker that discriminates MI from UA and
      predicts poor outcome in terms of disease severity and extent of disease
      complications. 

PMID- 25616487
TI  - Optimal doses of methotrexate combined with anti-TNF therapy to maintain clinical
      remission in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Methotrexate (MTX) is sometimes used as part of combination
      therapy for the treatment of inflammatory bowel disease [IBD]; however, the
      optimal MTX dose for combination therapy has not been established. This study
      compared the efficacy of lower-dose and higher-dose MTX with anti tumor necrosis
      factor alpha (anti-TNF) therapy among IBD patients. METHODS: Retrospective chart
      review was performed of 88 IBD patients at our center between 2010 and 2013. Low
      dose MTX was defined as <= 12.5mg/week and high-dose MTX as 15-25mg/week.
      Patients who met the criteria for clinical remission [Harvey-Bradshaw Index <= 4,
      Simple Clinical Colitis Activity Index <= 2] at baseline were followed for up to
      42 months. Chart review occurred in 6-month intervals. The primary outcome was
      consecutive months in remission prior to relapse. Secondary outcomes included
      other indicators of worsening disease [endoscopic inflammation, steroid use,
      therapy escalation/addition, or surgery] and adverse events. Regression analysis
      and Kaplan-Meier survival analysis were completed. RESULTS: We identified 73
      [83%] dual-therapy patients, of whom 32 low-dose and 14 high-dose individuals
      achieved remission. When compared with high-dose patients, low-dose patients were
      more likely to relapse [log-rank test, p < 0.01]. Secondary indicators of
      worsening disease occurred during 34.4% of low-dose review periods and 31.4% of
      high-dose review periods [p = 0.67]; 3/52 [6%] low-dose patients and 3/21 [14%]
      high-dose patients [p = 0.34] discontinued MTX therapy due to adverse events.
      CONCLUSIONS: When combined with anti-TNF therapy, MTX at doses of >12.5mg/week
      was more effective at maintaining clinical remission than lower doses. These
      findings will guide management of combination therapy in IBD patients.

PMID- 25616486
TI  - Developmental determinants in non-communicable chronic diseases and ageing.
AB  - Prenatal and peri-natal events play a fundamental role in health, development of
      diseases and ageing (Developmental Origins of Health and Disease (DOHaD)).
      Research on the determinants of active and healthy ageing is a priority to: (i)
      inform strategies for reducing societal and individual costs of an ageing
      population and (ii) develop effective novel prevention strategies. It is
      important to compare the trajectories of respiratory diseases with those of other
      chronic diseases. 

PMID- 25616489
TI  - Venous Thromboembolism in Patients Undergoing Shoulder Arthroscopy: Findings From
      the RECOS Registry.

PMID- 25616490
TI  - Effects of Hyperbaric and Decompression Stress on Blood Coagulation and
      Fibrinolysis: Comparison of Thromboelastography and Thromboelastometry.
AB  - Hyperbaric and decompression stress from diving impairs blood coagulation and
      fibrinolysis. We hypothesized that thromboelastography (TEG) and rotational
      thromboelastometry (ROTEM) were suitable to characterize the effects of stress on
      global hemostatic profiles. We thus conducted a comparative study of the
      hyperbaric effects on human coagulation using TEG and ROTEM. Maximum clot
      strength (maximum amplitude [MA]) and clot lysis (lysis index at time 30 minutes
      [LI30]) were reduced as indicated by TEG MA and EXTEM LI30, respectively. The
      relative changes in coagulation and fibrinolysis by the hyperbaric effects of
      diving were indicated by reduced TEG reaction time R at 5 hours, MA at 24 hours
      postdive, and reduced EXTEM coagulation time at 15 minutes postdive as well as
      decreased fibrinolysis (EXTEM LI30) at all postdiving time points investigated.
      Comparison of the parameter values and the diving-induced changes in each
      parameter between TEG and ROTEM showed both differences and correlations. The
      discrepancies between the 2 systems may be due to the different assay reagents
      used. Future studies will seek to further elucidate the changes in blood
      coagulation and fibrinolysis following varying levels of hyperbaric and
      decompression stress. 

PMID- 25616491
TI  - Carum induced hypothyroidism: an interesting observation and an experiment.
AB  - Carum carvi is a widely available herb that has been used as a food additive and
      as a medication in traditional medicine for many years. Its potential biological
      effects include analgesic, anti-inflammatory, anti-anxiety and antispasmodic
      activities. We report a patient with papillary thyroid carcinoma who were under
      treatment with levothyroxine and experienced an elevated TSH level by ingestion
      of Carum carvi. TSH level was increased to 60.3 mIU/L with no change in
      levothyroxine dosage and decreased to normal range after discontinuation of the
      Carum carvi. Observing this dramatic change in TSH level by carum ingestion,
      carum carvi capsules was produced and one of the researcher tried the medication
      on herself with a dose of 40 mg/kg/day. She had a history of hypothyroidism and
      was taking 100 ugr/day of levothyroxine. TSH was markedly increased 2 weeks after
      ingestion of Carum carvi and returned to normal range 5 months after
      discontinuation of it. This case report shows the effect of consumption of Carum
      carvi in increasing TSH level in hypothyroid patients treating with
      levothyroxine. The exact mechanism of action of carum carvi remains unknown.

PMID- 25616493
TI  - Conservative management of vesico-vaginal fistula after uterine and partial
      bladder necrosis due to embolization as a treatment for postpartum hemorrhage.

PMID- 25616492
TI  - Action of the multifunctional peptide BP100 on native biomembranes examined by
      solid-state NMR.
AB  - Membrane composition is a key factor that regulates the destructive activity of
      antimicrobial peptides and the non-leaky permeation of cell penetrating peptides
      in vivo. Hence, the choice of model membrane is a crucial aspect in NMR studies
      and should reflect the biological situation as closely as possible. Here, we
      explore the structure and dynamics of the short multifunctional peptide BP100
      using a multinuclear solid-state NMR approach. The membrane alignment and
      mobility of this 11 amino acid peptide was studied in various synthetic lipid
      bilayers with different net charge, fluidity, and thickness, as well as in native
      biomembranes harvested from prokaryotic and eukaryotic cells. (19)F-NMR provided
      the high sensitivity and lack of natural abundance background that are necessary
      to observe a labelled peptide even in protoplast membranes from Micrococcus
      luteus and in erythrocyte ghosts. Six selectively (19)F-labeled BP100 analogues
      gave remarkably similar spectra in all of the macroscopically oriented membrane
      systems, which were studied under quasi-native conditions of ambient temperature
      and full hydration. This similarity suggests that BP100 has the same surface
      bound helical structure and high mobility in the different biomembranes and model
      membranes alike, independent of charge, thickness or cholesterol content of the
      system. (31)P-NMR spectra of the phospholipid components did not indicate any
      bilayer perturbation, so the formation of toroidal wormholes or micellarization
      can be excluded as a mechanism of its antimicrobial or cell penetrating action.
      However, (2)H-NMR analysis of the acyl chain order parameter profiles showed that
      BP100 leads to considerable membrane thinning and thereby local destabilization. 

PMID- 25616494
TI  - (1)H, (15)N, (13)C resonance assignment of human osteopontin.
AB  - Osteopontin (OPN) is a 33.7 kDa intrinsically disordered protein and a member of
      the SIBLING family of proteins. OPN is bearing a signal peptide for secretion
      into the extracellular space, where it exerts its main physiological function,
      the control of calcium biomineralization. It is often involved in tumorigenic
      processes influencing proliferation, migration and survival, as well as the
      adhesive properties of cancer cells via CD44 and integrin signaling pathways.
      Here we report the nearly complete NMR chemical shift assignment of recombinant
      human osteopontin. 

PMID- 25616496
TI  - Exosomes: nanoshuttles to the future of BioMedicine.

PMID- 25616495
TI  - Objectively measured physical activity in two-year-old children - levels,
      patterns and correlates.
AB  - BACKGROUND: The aim was to describe levels, patterns and correlates of physical
      activity and sedentary behavior in a sample of Swedish children, two years of
      age, with normal weight, overweight and obese parents. METHODS: Data from 123
      children, 37 with normal-weight parents and 86 with overweight/obese parents,
      enrolled in the Early Stockholm Obesity Prevention Project study was used.
      Children wore an Actigraph GT3X+ accelerometer for seven days. Average activity
      (counts per minute), number of steps and time spent in low and high-intensity
      physical activity and in sedentary was assessed. Differences between weekdays and
      weekend days were examined as were correlations with sex, body mass index (BMI),
      motor skills and family-related factors. RESULTS: Children were active at high
      intensity 11% of the day. On average 55% of the day was spent being sedentary.
      Number of steps and time in low-intensity physical activity differed between
      weekdays and weekend days: on weekdays, 363 more steps (p = 0.01) and six more
      minutes in low physical activity (p = 0.04). No differences were found for any
      physical activity or sedentary behavior variable by sex, BMI, motor skills or any
      family-related variable (p = 0.07 - 0.95). CONCLUSIONS: Two-year-old children
      have an intermittent activity pattern, that is almost similar on weekdays and
      they spend about half of the daytime active. The absence of any association with
      sex, BMI, motor skills or parental factors indicates that the individual
      variation in this age group is primarily due to endogenous factors. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01198847 .

PMID- 25616497
TI  - Family support, family stress, and suicidal ideation in a combat-exposed sample
      of Operation Enduring Freedom/Operation Iraqi Freedom veterans.
AB  - BACKGROUND AND OBJECTIVES: Deployment-related risk factors for suicidal ideation
      among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans
      have received a great deal of attention. Studies show that mental health symptoms
      mediate the association between most deployment stressors and suicidal ideation;
      however, family-related factors during deployment are largely unexplored. We
      examined posttraumatic stress disorder (PTSD) and depression symptoms as
      mediators of the associations between deployment family support and stress and
      post-deployment suicidal ideation in combat-exposed OEF/OIF veterans. DESIGN:
      National cross-sectional mail survey. METHODS: 1046 veterans responded to the
      survey. The sample for this study was 978 veterans who experienced combat.
      Regression-based path analyses were conducted. RESULTS: Family support and stress
      had direct associations with suicidal ideation. When PTSD and depression symptoms
      were examined as mediators of these associations, results revealed significant
      indirect paths through these symptoms. CONCLUSIONS: This study contributes to the
      literature on suicidal ideation risk factors among OEF/OIF veterans. Deployment
      family support and family stress are associated with suicidal ideation; however
      these associations occur primarily through mental health symptomatology,
      consistent with findings observed for other deployment factors. This research
      supports ongoing efforts to treat mental health symptomatology as a means of
      suicide prevention.

PMID- 25616498
TI  - Additive clinical value of serum brain-derived neurotrophic factor for prediction
      of chronic heart failure outcome.
AB  - The importance of the central nervous system in cardiovascular events has been
      recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the
      neurotrophic factor family, is involved in depression mechanisms and also in
      stress and anxiety. Because BDNF is reported about cardioprotective role, we
      elucidated whether BDNF is associated with cardiovascular events in patients with
      chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with
      CHF and 23 control subjects. The patients were followed to register cardiac
      events for a median of 426 days. BDNF was significantly lower in CHF patients
      than in control subjects (25.8 +/- 8.4 vs 14.7 +/- 8.4, P < 0.0001). Serum BDNF
      was also lower in patients with cardiac events than in event-free patients (16.1
      +/- 8.0 vs 12.5 +/- 8.5, P < 0.0001). The cutoff value of BDNF was determined by
      performing receiver operating characteristic curve analysis. Kaplan-Meier
      analysis demonstrated that patients with low levels of BDNF experienced higher
      rates of cardiac events than those with high levels of BDNF. Multivariate Cox
      hazard analysis demonstrated that low BDNF levels (<=12.4 ng/mL) were an
      independent prognostic factor for cardiac events (hazard ratio 2.932, 95 %
      confidence interval 1.622-5.301; P = 0.0004). Adding levels of BDNF to the model
      with BNP levels, age, and eGFR for the prediction of cardiac events yielded
      significant net reclassification improvement of 0.429 (P < 0.001) and an
      integrated discrimination improvement of 0.101 (P < 0.001). Low serum BDNF levels
      were found in patients with CHF, and these levels were found to be independently
      associated with an increased risk of cardiac events.

PMID- 25616499
TI  - The Cell Factory Aspergillus Enters the Big Data Era: Opportunities and
      Challenges for Optimising Product Formation.
AB  - Living with limits. Getting more from less. Producing commodities and high-value
      products from renewable resources including waste. What is the driving force and
      quintessence of bioeconomy outlines the lifestyle and product portfolio of
      Aspergillus, a saprophytic genus, to which some of the top-performing microbial
      cell factories belong: Aspergillus niger, Aspergillus oryzae and Aspergillus
      terreus. What makes them so interesting for exploitation in biotechnology and how
      can they help us to address key challenges of the twenty-first century? How can
      these strains become trimmed for better growth on second-generation feedstocks
      and how can we enlarge their product portfolio by genetic and metabolic
      engineering to get more from less? On the other hand, what makes it so
      challenging to deduce biological meaning from the wealth of Aspergillus -omics
      data? And which hurdles hinder us to model and engineer industrial strains for
      higher productivity and better rheological performance under industrial
      cultivation conditions? In this review, we will address these issues by
      highlighting most recent findings from the Aspergillus research with a focus on
      fungal growth, physiology, morphology and product formation. Indeed, the last
      years brought us many surprising insights into model and industrial strains. They
      clearly told us that similar is not the same: there are different ways to make a
      hypha, there are more protein secretion routes than anticipated and there are
      different molecular and physical mechanisms which control polar growth and the
      development of hyphal networks. We will discuss new conceptual frameworks derived
      from these insights and the future scientific advances necessary to create value
      from Aspergillus Big Data.

PMID- 25616501
TI  - Effects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis
      induction.
AB  - Curine is a natural alkaloid isolated from Chondrodendron platyphyllum and it has
      been reported that this alkaloid has vasodilatory and anti-inflammatory effects.
      The aim of this study is to analyze the cytotoxic effects of curine in cancer
      cell lines HL-60, K562, and HT-29, and in primary cultures of peripheral blood
      mononuclear cells (PBMC). Cells were treated with curine (from 3 to 15 uM) for 24
      and 48 h. Cell viability was analyzed by the 3-(4,5-dimethylthiazole-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) test and flow cytometry with propidium iodide
      (PI) assay. To assess the type of cell death induced in HL-60, the cell cycle,
      morphological, and biochemical alterations were analyzed, which were determined
      by differential staining with acridine orange/ethidium bromide, and annexin V/PI
      double-labeling and change in mitochondrial membrane potential assays. Curine
      demonstrated a potent cytotoxic effect on leukemic cell lines (HL-60 and K562).
      Its cytotoxic effects in HL-60 cells was related to plasma membrane damage and
      cell cycle arrest at the G1 phase from 43.4 +/- 1.0 to 56.7 +/- 1.4 % (p < 0.05).
      Curine (15 MUM) also increased the apoptotic cells number by around 60 % in HL-60
      cells and caused phosphatidylserine externalization, inducing about 57 % of
      apoptosis. Moreover, this alkaloid provoked 20 % of mitochondrial membrane
      depolarization. We conclude that curine presented a cytotoxic effect and induced
      apoptosis in HL-60 cells. Thus, it can be considered a promising pharmacological
      drug. 

PMID- 25616500
TI  - Role of Kruppel-like factors in cancer stem cells.
AB  - Cancer stem cells (CSCs), or cancer cells with stem cell properties, are a rare
      population of tumor bulk and are recognized to be responsible for cancer
      recurrence, drug resistance, and metastasis. However, the molecular mechanisms of
      how to regulate the differentiation and self-renewing of CSCs are poorly
      understood. Kruppel-like factors (KLFs) are essential DNA-binding transcriptional
      regulators with diverse functions in various cellular processes, including
      differentiation, proliferation, inflammation, migration, and pluripotency. Recent
      progress has highlighted the significance of KLFs in tumor progression and CSCs.
      The regulatory functions of KLFs in the development of cancer and CSCs have
      become a burgeoning area of intense research. In this review, we summarize the
      current understanding and progress of the transcriptional regulation of KLFs in
      CSCs and discuss the functional implications of targeting CSCs by KLFs for cancer
      therapeutics. 

PMID- 25616502
TI  - Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a
      triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var.
      grisea.
AB  - In the present study, siaresinolic acid (siaresinol, SA) was isolated from the
      leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti
      inflammatory activity. The antinociceptive effect of SA was investigated in mice
      using different animal models to study pain. In the acetic acid-induced writhing
      test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h
      before a pain stimulus significantly reduced the nociceptive response (by 42.3,
      68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with
      yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive
      effect induced by SA in the writhing test, suggesting that the K(+)ATP channel
      pathway might be involved in its mechanism of action. In the formalin test, SA (1
      mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating
      an anti-inflammatory effect. In the hot plate test, there was no significant
      difference in nociceptive behavior. In the rota-rod test, it was verified that a
      high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice.
      In the pleurisy model, induced by carrageenan, treatment with SA inhibited
      important events involved in inflammatory responses, namely leukocyte influx,
      plasma leakage, and increased inflammatory mediators (TNF-alpha, IL-1beta, and
      chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not
      cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at
      concentrations ranging from 1 to 200 MUg/mL. These results suggest, for the first
      time, that SA attenuates nociceptive behavior through mechanisms involving
      receptors for ATP-dependent potassium channels, in addition to suppressing acute
      inflammatory responses. 

PMID- 25616504
TI  - Schizophrenia: Nutrition and Alternative Treatment Approaches.

PMID- 25616503
TI  - Jumping to Conclusions About the Beads Task? A Meta-analysis of Delusional
      Ideation and Data-Gathering.
AB  - It has been claimed that delusional and delusion-prone individuals have a
      tendency to gather less data before forming beliefs. Most of the evidence for
      this "jumping to conclusions" (JTC) bias comes from studies using the "beads
      task" data-gathering paradigm. However, the evidence for the JTC bias is mixed.
      We conducted a random-effects meta-analysis of individual participant data from
      38 clinical and nonclinical samples (n = 2,237) to investigate the relationship
      between data gathering in the beads task (using the "draws to decision" measure)
      and delusional ideation (as indexed by the "Peters et al Delusions Inventory";
      PDI). We found that delusional ideation is negatively associated with data
      gathering (r(s) = -0.10, 95% CI [-0.17, -0.03]) and that there is heterogeneity
      in the estimated effect sizes (Q-stat P = .03, I(2) = 33). Subgroup analysis
      revealed that the negative association is present when considering the 23 samples
      (n = 1,754) from the large general population subgroup alone (r(s) = -0.10, 95%
      CI [-0.18, -0.02]) but not when considering the 8 samples (n = 262) from the
      small current delusions subgroup alone (r(s) = -0.12, 95% CI [-0.31, 0.07]).
      These results provide some provisional support for continuum theories of
      psychosis and cognitive models that implicate the JTC bias in the formation and
      maintenance of delusions.

PMID- 25616505
TI  - Meta-analysis of Cognitive Impairment in First-Episode Bipolar Disorder:
      Comparison With First-Episode Schizophrenia and Healthy Controls.
AB  - Neurocognitive deficits are evident both in established schizophrenia and bipolar
      disorder (BP). However, it has been suggested that schizophrenia, but not BP, is
      characterized by neurodevelopmental abnormalities that can lead to cognitive
      deficits at the earliest stages of the illness. The aim of this meta-analytic
      review was to compare neurocognitive deficits in first-episode BP (FEBP) with
      healthy controls and first-episode schizophrenia (FES) patients. The current meta
      analysis included a total of 22 adult studies and involved comparisons of 533
      FEBP patients with 1417 healthy controls and 605 FEBP and 822 FES patients. FEBP
      patients were significantly impaired in all cognitive domains (d = 0.26-0.80) and
      individual tasks (d = 0.22-0.66) investigated. FES patients significantly
      underperformed FEBP patients in most cognitive domains (d = 0.05-0.63) and on
      individual tasks (d = 0.13-0.77). Neuropsychological impairment, which is
      comparable to chronic BP, was evident in FEBP. Similar to chronic patients,
      cognitive functions in FEBP lie intermediate between FES and healthy controls.
      Neurodevelopmental factors are likely to play a significant role not only in
      schizophrenia but also in BP. 

PMID- 25616507
TI  - Variations in parathyroid hormone concentration in patients with low 25
      hydroxyvitamin D and its correction in patients with hip fracture.

PMID- 25616506
TI  - Plasma dimethylglycine, nicotine exposure and risk of low bone mineral density
      and hip fracture: the Hordaland Health Study.
AB  - In the large community-based Hordaland Health Study, low plasma dimethylglycine
      was associated with low bone mineral density in both middle-aged and elderly
      subjects and to an increased risk of subsequent hip fracture among the elderly.
      These associations seemed to be particularly strong among subjects exposed to
      nicotine. INTRODUCTION: Dimethylglycine (DMG) is a product of the choline
      oxidation pathway and formed from betaine during the folate-independent
      remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are
      associated with atherosclerotic cardiovascular disease and inflammation, which in
      turn are related to osteoporosis. High plasma total Hcy and low plasma choline
      are associated with low bone mineral density (BMD) and hip fractures, but the
      role of plasma DMG in bone health is unknown. METHODS: We studied the
      associations of plasma DMG with BMD among 5315 participants (46-49 and 71-74
      years old) and with hip fracture among 3310 participants (71-74 years old)
      enrolled in the Hordaland Health Study. RESULTS: In age and sex-adjusted logistic
      regression models, subjects in the lowest versus highest DMG tertile were more
      likely to have low BMD (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.43
      1.99). The association was stronger in participants exposed compared to those
      unexposed to nicotine (OR 2.31, 95% CI 1.73-3.07 and OR 1.43, 95% CI 1.16-1.75,
      respectively, p interaction = 0.008). In the older cohort, Cox regression
      analyses adjusted for sex showed that low plasma DMG was associated with an
      increased risk of hip fracture (hazard ratio [HR] 1.70, 95% CI 1.28-2.26). A
      trend toward an even higher risk was found among women exposed to nicotine (HR
      3.41, 95% CI 1.40-8.28). CONCLUSION: Low plasma DMG was associated with low BMD
      and increased risk of hip fractures. A potential effect modification by nicotine
      exposure merits particular attention.

PMID- 25616508
TI  - Fracture incidence in a large cohort of men age 30 years and older with
      osteoporosis.
AB  - In this large retrospective study of men with presumed osteoporosis, we estimate
      the rate of osteoporosis-related fractures in men age >=30 years. Our results
      suggest that spine and hip fractures continue to be a considerable disease burden
      for osteoporotic men of all ages. INTRODUCTION: The purposes of this study were
      to describe a cohort of men with presumed osteoporosis and estimate the incidence
      rates of fractures by age. METHODS: Using US administrative claims data, we
      identified 43,813 men >=30 years old with an osteoporosis diagnosis or use of an
      osteoporosis medication. Men were followed for a minimum of 12 months after
      diagnosis or treatment of osteoporosis (index date), until the earliest of
      fracture (hip, spine, pelvis, distal femur, humerus, wrist, forearm),
      disenrollment, or study end date. RESULTS: During the study period, there were
      3834 first fractures following the index date and 3303 fractures in the 6-month
      period prior to the diagnosis/treatment of osteoporosis. Incidence rates of
      osteoporosis-related fracture, estimated from the index date onward, increased
      with age, although did not significantly differ from one another in younger age
      groups (30-49 and 50-64 years). Spine fractures had the highest incidence rate in
      men across all age groups, increasing from 10.8 per 100,000 person-years (p-yrs)
      (95% confidence interval (CI) 9.1, 12.7), 12.2 per 100,000 p-yrs (95% CI 11.2,
      13.3), and 15.3 per 100,000 p-yrs (95% CI 13.8, 16.9) in men 30-49, 50-64, and 65
      74 years to 33.4 per 100,000 p-yrs (95% CI 31.5, 35.4) in men >=75 years. Hip
      fractures were the second most common, with the incidence rate reaching 16.2 per
      100,000 (95% CI 14.9, 17.6) in the >=75-year group. CONCLUSION: These incidence
      rates suggest that spine and hip fractures are a considerable disease burden for
      men of all ages diagnosed and/or treated for osteoporosis.

PMID- 25616509
TI  - Association between low C-peptide and low lumbar bone mineral density in
      postmenopausal women without diabetes.
AB  - In this population-based, cross-sectional study in Italian postmenopausal females
      not affected by diabetes, we showed a link between serum C-peptide and lumbar
      bone mineral density, suggesting that C-peptide exerts an insulin-independent
      effect on bone mass. INTRODUCTION: It is well known that type 1 (T1) diabetes,
      characterized by insulin and C-peptide deficiency, is associated with a low
      lumbar bone mineral density and an increased risk for fracture. While a role for
      insulin in the pathogenesis of osteoporosis has been demonstrated, the
      association between C-peptide and the bone mineral density has not been
      investigated. We conducted a study in a cohort of 84 postmenopausal women without
      diabetes to clarify the association between serum C-peptide and the lumbar bone
      mineral density. METHODS: Participants underwent a bone mineral density
      evaluation by DXA and biochemical analysis including the C-peptide assay.
      RESULTS: rteen percent of the population had osteoporosis and 38% had osteopenia.
      With ANOVA test, we showed that women with the lowest C-peptide concentration had
      lower lumbar mineral density in comparison to those in all other C-peptide
      concentration group (p = 0.02 among groups after adjustment). The univariate and
      multivariate analysis showed that C-peptide was positively associated with both
      lumbar T-score and Z-score besides other well-known factors like age (with T
      score p < 0.001; beta = -0.38) and BMI (with T-score p = 0.009; beta = 0.34),
      while insulin was not correlated with the lumbar bone mineral density. The area
      under the receiver operating characteristic (ROC) curve for C-peptide to predict
      the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013). CONCLUSIONS:
      These results suggest that C-peptide may exert an insulin- and BMI-independent
      effect on lumbar bone mineral density and that further large-scale studies are
      needed in order to clarify its role in bone mineralization especially in subjects
      without diabetes.

PMID- 25616510
TI  - Research literature production on nursing competences from 1981 till 2012: A
      bibliometric snapshot.
AB  - BACKGROUND: When nurse education has moved away from a hospital based
      apprenticeship to a higher education institutions and new EU legislature enabled
      nurse workforce mobility, the term "competence" became an important concept in
      nurse education and practice. However, there is still a lot of confusion about
      its definition, how it should be assessed and implemented and which competences
      does a contemporary nurse need. OBJECTIVES: To find publishing patterns in the
      nursing competence research literature production, focusing on publishing
      dynamics, identifying prolific research entities, most cited papers, and
      visualising the content of the research. DESIGN AND DATA SOURCES: A bibliometric
      analysis of 370 information sources (288 original papers and 82 review articles)
      found in the Scopus database using the search string "nursing competenc*" for the
      period 1981-2012 was conducted. The SciMago database was used to identify country
      and source title ranks. METHODS: Common elements of bibliometric data were
      extracted from each information source. Descriptive, correspondence and text
      analyses were used on the retrieved bibliometric data. RESULTS: The production of
      research literature has a positive trend. The research on nursing competences is
      being performed on all five continents, however is not yet published in top
      journals. Most prolific countries are the United States of America, the United
      Kingdom and Australasia, and most prolific source titles are the Journal of
      clinical nursing, the Journal of nursing education and Public health nursing. The
      results confirmed the still persisting confusion in the definition of the
      competence and the emergence of the need for defining new nursing competences.
      CONCLUSIONS: Study confirmed that there are still open questions in the nursing
      competence research that will require actions on different levels including
      policy makers, educators and practising nurses.

PMID- 25616511
TI  - Genome-Engineering Tools to Establish Accurate Reporter Cell Lines That Enable
      Identification of Therapeutic Strategies to Treat Friedreich's Ataxia.
AB  - Friedreich's ataxia is a neurodegenerative disease caused by deficiency of the
      mitochondrial protein frataxin. This deficiency results from expansion of a
      trinucleotide repeat in the first intron of the frataxin gene. Because this
      repeat expansion resides in an intron and hence does not alter the amino acid
      sequence of the frataxin protein, gene reactivation could be of therapeutic
      benefit. High-throughput screening for frataxin activators has so far met with
      limited success because current cellular models may not accurately assess
      endogenous frataxin gene regulation. Here we report the design and validation of
      genome-engineering tools that enable the generation of human cell lines that
      express the frataxin gene fused to a luciferase reporter gene from its endogenous
      locus. Performing a pilot high-throughput genomic screen in a newly established
      reporter cell line, we uncovered novel negative regulators of frataxin
      expression. Rational design of small-molecule inhibitors of the identified
      frataxin repressors and/or high-throughput screening of large siRNA or compound
      libraries with our system may yield treatments for Friedreich's ataxia. 

PMID- 25616512
TI  - Real-time continuous glucose monitoring versus conventional glucose monitoring in
      critically ill patients: a systematic review study protocol.
AB  - INTRODUCTION: Stress-induced hyperglycaemia, which has been shown to be
      associated with an unfavourable prognosis, is common among critically ill
      patients. Additionally, it has been reported that hypoglycaemia and high glucose
      variabilities are also associated with adverse outcomes. Thus, continuous glucose
      monitoring (CGM) may be the optimal method to detect severe hypoglycaemia,
      hyperglycaemia and decrease glucose excursion. However, the overall accuracy and
      reliability of CGM systems and the effects of CGM systems on glucose control and
      prognosis in critically ill patients remain inconclusive. Therefore, we will
      conduct a systematic review and meta-analysis to clarify the associations between
      CGM systems and clinical outcome. METHODS AND ANALYSIS: We will search PubMed,
      EMBASE and the Cochrane Library from inception to October 2014. Studies comparing
      CGM systems with any other glucose monitoring methods in critically ill patients
      will be eligible for our meta-analysis. The primary endpoints include the
      incidence of hypoglycaemia and hyperglycaemia, mean glucose level, and percentage
      of time within the target range. The second endpoints include intensive care unit
      (ICU) mortality, hospital mortality, duration of mechanical ventilation, length
      of ICU and hospital stay, and the Pearson correlation coefficient and the results
      of error grid analysis. In addition, we will record all complications (eg,
      acquired infections) in control and intervention groups and local adverse events
      in intervention groups (eg, bleeding or infections). ETHICS AND DISSEMINATION:
      Ethics approval is not required as this is a protocol for a systematic review.
      The findings will be disseminated in a peer-reviewed journal and presented at a
      relevant conference. TRIAL REGISTRATION NUMBER: PROSPERO registration number:
      CRD42014013488.

PMID- 25616513
TI  - University silenced student's concerns about research, memo suggests.

PMID- 25616514
TI  - To what extent does urbanisation affect fragmented grassland functioning?
AB  - Urbanisation creates altered environments characterised by increased human
      habitation, impermeable surfaces, artificial structures, landscape fragmentation,
      habitat loss, resulting in different resource loss pathways. The vulnerable Rand
      Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa,
      has been extensively affected and transformed by urbanisation, agriculture, and
      mining. Grassland fragments in urban areas are often considered to be less
      species rich and less functional than in the more untransformed or "natural"
      exurban environments, and are therefore seldom a priority for conservation.
      Furthermore, urban grassland fragments are often being more intensely managed
      than exurban areas, such as consistent mowing in open urban areas. Four
      urbanisation measures acting as indicators for patterns and processes associated
      with urban areas were calculated for matrix areas surrounding each selected
      grassland fragment to quantify the position of each grassland remnant along an
      urbanisation gradient. The grassland fragments were objectively classified into
      two classes of urbanisation, namely "exurban" and "urban" based on the
      urbanisation measure values. Grazing was recorded in some exurban grasslands and
      mowing in some urban grassland fragments. Unmanaged grassland fragments were
      present in both urban and exurban areas. Fine-scale biophysical landscape
      function was determined by executing the Landscape Function Analysis (LFA)
      method. LFA assesses fine-scale landscape patchiness (entailing resource
      conserving potential and erosion resistance) and 11 soil surface indicators to
      produce three main LFA parameters (stability, infiltration, and nutrient
      cycling), which indicates how well a system is functioning in terms of fine-scale
      biophysical soil processes and characteristics. The aim of this study was to
      determine the effects of urbanisation and associated management practices on fine
      scale biophysical landscape function of urban and exurban grassland fragments, as
      well as to determine the potential for the use of LFA in decision-making
      involving the conservation of grassland fragments. The results indicated that the
      occurrence, size and characteristics of vegetated patches, and especially the
      presence of litter abundances, were the main factors determining differences in
      the LFA indices. Furthermore, mowing resulted in the overall fine-scale
      biophysical indices being higher for some of the urban grassland fragments. This
      implied that it is not necessarily the influence of urbanisation entailing high
      or low resource conserving patchiness and patch quality, but rather the
      management practices associated with urban and exurban areas. Therefore, from a
      conservation point of view, the grassland fragments in the City of Potchefstroom
      are just as conservable (on a biophysical function level involving soil
      processes) than the more "natural" exurban grassland fragments. 

PMID- 25616516
TI  - Response to the letter by Minghui Peng, MD, Baohua Jiao, MD.

PMID- 25616515
TI  - Attention Deficit Hyperactivity Disorder symptoms and smoking trajectories: race
      and gender differences.
AB  - PURPOSE: This study examined the influence of Attention Deficit Hyperactivity
      Disorder (ADHD) symptoms severity and directionality (hyperactive-impulsive
      symptoms relative to inattentive symptoms) on trajectories of the probability of
      current (past month) smoking and the number of cigarettes smoked from age 13 to
      32. Racial and gender differences in the relationship of ADHD symptoms and
      smoking trajectories were also assessed. METHODS: A subsample of 9719 youth
      (54.5% female) was drawn from the National Longitudinal Study of Adolescent to
      Adult Health (Add Health). Cohort sequential design and zero-inflated Poisson
      (ZIP) latent growth modeling were used to estimate the relationship between ADHD
      directionality and severity on smoking development. RESULTS: ADHD severity's
      effect on the likelihood of ever smoking cigarettes at the intercept (age 13) had
      a greater impact on White males than other groups. ADHD severity also had a
      stronger influence on the initial number of cigarettes smoked at age 13 among
      Hispanic participants. The relationships between ADHD directionality (hyperactive
      impulsive symptoms relative to inattentive symptoms) and a higher number of
      cigarettes smoked at the intercept were stronger among Hispanic males than
      others. Gender differences manifested only among Whites. CONCLUSION: ADHD
      severity and directionality had unique effects on smoking trajectories. Our
      results also highlight that the risk of ADHD symptoms may differ by race and
      gender.

PMID- 25616517
TI  - Body mass index and waist circumference rather than body adiposity index are
      better surrogates for body adiposity in a Chinese population.
AB  - BACKGROUND: Several studies have found that body adiposity index (BAI) is a
      better index of body adiposity than body mass index (BMI) in African and Mexican
      American adults. This study aims to evaluate the ability of BAI to predict body
      adiposity in Chinese children and adults. MATERIALS AND METHODS: In total, 2425
      children and 5726 adults were recruited from rural China. All participants
      completed whole-body dual-energy X-ray absorptiometry (DXA) and anthropometric
      measures. The correlation of BMI, BAI, and waist circumference (WC) to DXA
      adiposity indexes was performed across sex-specific adult and age- and sex
      specific child cohorts, using Spearman correlation and linear regression models,
      respectively. RESULTS: Both BMI and WC had a higher correlation with all
      adiposity indexes (whole body fat, percent body fat [Bfat%], trunk fat, and
      percent trunk fat [Tfat%]) measured by DXA than did BAI in both adults and
      children. Meanwhile, most of the linear regression model associations for BMI
      with Bfat% and Tfat% had a greater adjusted R(2) than those for BAI among both
      children and adults. CONCLUSION: This study indicates that BMI and WC are better
      tools than BAI for estimating whole body fat and central body fat in a Chinese
      population.

PMID- 25616518
TI  - Ultrasound-guided nasogastric feeding tube placement in critical care patients.
AB  - BACKGROUND: Nasogastric feeding tube (NGT) placement is a common practice
      performed in intensive care units (ICUs). Complications due to the improper
      placement of NGT are well known. In this prospective descriptive study, the
      effectiveness of ultrasound (US)-guided NGT placement was investigated. MATERIALS
      AND METHODS: Fifty-six mechanically ventilated patients monitored in the ICU were
      included. A linear US probe was transversely placed just cranial to the
      suprasternal notch, and the concentric layers of the esophagus were attempted to
      be viewed on the posterolateral side of the trachea (generally left) by shifting
      the probe. If the esophagus can be seen, an attempt was made to insert the NGT
      under real-time visualization of ultrasonography. Furthermore, gastric placement
      of the NGT tip was confirmed with abdominal radiograph. RESULTS: A total of 56
      patients were included in the study. For 52 (92.8%), the NGT image was obtained
      during placement within the esophagus. For 3 (5.3%), the esophagus could not be
      seen by US, and NGT was placed blindly. For 1 patient, we could not detect
      passing of the NGT into the stomach despite the successful visualization of
      esophagus. In this patient, NGT was radiographically detected in the trachea
      after the procedure. CONCLUSION: This study revealed that passing of the NGT
      through the esophagus could be visualized at a high rate in real-time US among
      ICU patients. These data suggest that ultrasonographic visualization of the upper
      esophagus during NGT insertion can be used as an adjuvant method for confirmation
      of correct placement.

PMID- 25616519
TI  - Safety and Tolerability of Enteral Protein Supplementation for Infants With Brain
      Injury.
AB  - BACKGROUND: We hypothesized that enteral protein supplementation in infants with
      brain injury would be safe and well tolerated and improve growth. MATERIALS AND
      METHODS: Twenty-five infants with perinatal brain injury were randomized to a
      high-protein (4 g/kg/d) or standard-protein diet and followed for 12 months.
      RESULTS: The whey protein powder was well tolerated by 9 of the 13 infants in the
      high-protein group, and no adverse events related to the supplement were seen.
      The protein group had higher serum urea nitrogen at 10 and 30 days after study
      initiation but no difference in bicarbonate levels at either time point. Infants
      in the protein group maintained their weight z score from birth to 3 months of
      age, while infants in the standard group had a significant decrease in their
      weight z score over the same time period. CONCLUSION: These results suggest that
      enteral protein supplementation may reduce growth failure in infants with brain
      injury.

PMID- 25616520
TI  - Potential for proteomic approaches in determining efficacy biomarkers following
      administration of fish oils rich in omega-3 fatty acids: application in
      pancreatic cancers.
AB  - Pancreatic cancer is a disease with a significantly poor prognosis. Despite
      modern advances in other medical, surgical, and oncologic therapy, the outcome
      from pancreatic cancer has improved little over the last 40 years. To improve the
      management of this difficult disease, trials investigating the use of dietary and
      parenteral fish oils rich in omega-3 (omega-3) fatty acids, exhibiting proven
      anti-inflammatory and anticarcinogenic properties, have revealed favorable
      results in pancreatic cancers. Proteomics is the large-scale study of proteins
      that attempts to characterize the complete set of proteins encoded by the genome
      of an organism and that, with the use of sensitive mass spectrometric-based
      techniques, has allowed high-throughput analysis of the proteome to aid
      identification of putative biomarkers pertinent to given disease states. These
      biomarkers provide useful insight into potentially discovering new markers for
      early detection or elucidating the efficacy of treatment on pancreatic cancers.
      Here, our review identifies potential proteomic-based biomarkers in pancreatic
      cancer relating to apoptosis, cell proliferation, angiogenesis, and metabolic
      regulation in clinical studies. We also reviewed proteomic biomarkers from the
      administration of omega-3 fatty acids that act on similar anticarcinogenic
      pathways as above and reflect that proteomic studies on the effect of omega-3
      fatty acids in pancreatic cancer will yield favorable results.

PMID- 25616521
TI  - Retraction Note to: Evaluation of coracoclavicular stabilization of acute
      acromioclavicular joint dislocation with multistrand titanium cables.

PMID- 25616522
TI  - ASNM reply to letter of Eccher et al.

PMID- 25616524
TI  - The development of a protocol for post-mortem management of Ebola virus disease
      in the setting of developed countries.
AB  - The management of the recent Ebola virus disease (EVD) epidemic continues to pose
      currently insuperable challenges to health care providers in the resource
      deprived countries of West Africa. In an age where air travel facilitates rapid
      movement of people between countries and continents, there is an urgent
      requirement for health systems around the globe to develop management strategies
      and protocols in the event that EVD cases are suspected or confirmed. Departments
      of forensic pathology play an important, and underestimated, role in public
      health service delivery, particularly at times of novel infectious disease
      emergence. This role can include disease identification, characterization, and
      notification, as well as close engagement with agencies responsible for disease
      surveillance and treatment provision. A mass outbreak of EVD in the Western world
      is considered highly unlikely; however, there is clear responsibility on
      departments of forensic pathology to develop protocols for rapid assessment of
      sporadic or suspected cases while ensuring the health and safety of mortuary and
      pathology personnel. The Ontario Forensic Pathology Service and the Victorian
      Institute of Forensic Medicine have collaborated on the development of a protocol
      for management of EVD cases presenting at a scene or in the mortuary. It is hoped
      that this trans-national, inter-departmental exercise will serve as a model for
      future co-operative endeavors. The protocol has been distributed to forensic
      pathology departments around Australia and may be modified to accommodate local
      resource capabilities. 

PMID- 25616525
TI  - Strategies for the production of difficult-to-express full-length eukaryotic
      proteins using microbial cell factories: production of human alpha-galactosidase
      A.
AB  - Obtaining high levels of pure proteins remains the main bottleneck of many
      scientific and biotechnological studies. Among all the available recombinant
      expression systems, Escherichia coli facilitates gene expression by its relative
      simplicity, inexpensive and fast cultivation, well-known genetics and the large
      number of tools available for its biotechnological application. However,
      recombinant expression in E. coli is not always a straightforward procedure and
      major obstacles are encountered when producing many eukaryotic proteins and
      especially membrane proteins, linked to missing posttranslational modifications,
      proteolysis and aggregation. In this context, many conventional and
      unconventional eukaryotic hosts are under exploration and development, but in
      some cases linked to complex culture media or processes. In this context,
      alternative bacterial systems able to overcome some of the limitations posed by
      E. coli keeping the simplicity of prokaryotic manipulation are currently emerging
      as convenient hosts for protein production. We have comparatively produced a
      "difficult-to-express" human protein, the lysosomal enzyme alpha-galactosidase A
      (hGLA) in E. coli and in the psychrophilic bacterium Pseudoalteromonas
      haloplanktis TAC125 cells (P. haloplanktis TAC125). While in E. coli the
      production of active hGLA was unreachable due to proteolytic instability and/or
      protein misfolding, the expression of hGLA gene in P. haloplanktis TAC125 allows
      obtaining active enzyme. These results are discussed in the context of emerging
      bacterial systems for protein production that represent appealing alternatives to
      the regular use of E. coli and also of more complex eukaryotic systems.

PMID- 25616526
TI  - Development of a growth-dependent selection system for identification of L
      threonine aldolases.
AB  - Threonine aldolases (TAs) are useful enzymes for the synthesis of beta-hydroxy
      alpha-amino acids due to their capability to catalyze asymmetric aldol reactions.
      Starting from two prochiral compounds, an aldehyde and glycine, two chiral
      stereocenters were formed in a single step via C-C bond formation. Owing to poor
      diastereoselectivity and low activity, the enzymatic synthesis of beta-hydroxy
      alpha-amino acids by TAs is still a challenge. For identification of new TAs, a
      growth-dependent selection system in Pseudomonas putida KT2440 has been
      developed. This bacterium is able to use aromatic compounds such as benzaldehyde,
      which is the cleavage product of the TA-mediated retro-aldol reaction of
      phenylserine, as sole carbon source via the beta-ketoadipate pathway. With DL
      threo-beta-phenylserine as sole carbon source, this strain showed only slight
      growth in minimal medium. This growth deficiency can be restored by introducing
      and expressing genes encoding TAs. In order to develop a highly efficient
      selection system, the gene taPp of P. putida KT2440 encoding a TA was
      successfully deleted by replacement with an antibiotic resistance cassette.
      Different growth studies were carried out to prove the operability of the
      selection system. Genes encoding for L- and D-specific TAs (L-TA genes of
      Escherichia coli (ltaE) and Saccharomyces cerevisiae (gly1) and D-TA gene of
      Achromobacter xylosoxidans (dtaAX)) were introduced into the selection strain P.
      putida KT2440DeltataPp, followed by cultivation on minimal medium supplemented
      with DL-threo-beta-phenylserine. The results demonstrate that only the selection
      strains with plasmid-encoded L-TAs were able to grow on this racemic amino acid,
      whereas the corresponding strain harboring the gene coding for a D-specific TA
      showed no growth. In summary, it can be stated that a powerful screening tool was
      developed to identify easily by growth new L-specific threonine aldolases or
      other enzymes from genomic or metagenomic libraries liberating benzaldehyde. 

PMID- 25616528
TI  - Current progress on truffle submerged fermentation: a promising alternative to
      its fruiting bodies.
AB  - Truffle (Tuber spp.), also known as "underground gold," is popular in various
      cuisines because of its unique and characteristic aroma. Currently, truffle
      fruiting bodies are mostly obtained from nature and semi-artificial cultivation.
      However, the former source is scarce, and the latter is time-consuming, usually
      taking 4 to 12 years before harvest of the fruiting body. The truffle submerged
      fermentation process was first developed in Tang's lab as an alternative to its
      fruiting bodies. To the best of our knowledge, most reports of truffle submerged
      fermentation come from Tang's group. This review examines the current state of
      the truffle submerged fermentation process. First, the strategy to optimize the
      truffle submerged fermentation process is summarized; the final conditions
      yielded not only the highest reported truffle biomass but also the highest
      production of extracellular and intracellular polysaccharides. Second, the
      comparison of metabolites produced by truffle fermentation and fruiting bodies is
      presented, and the former were superior to the latter. Third, metabolites (i.e.,
      volatile organic compounds, equivalent umami concentration, and sterol) derived
      from truffle fermentation could be regulated by fermentation process
      optimization. These findings indicated that submerged fermentation of truffles
      can be used for commercial production of biomass and metabolites as a promising
      alternative to generating its fruiting bodies in bioreactor. 

PMID- 25616527
TI  - Effect and behaviour of different substrates in relation to the formation of
      aerobic granular sludge.
AB  - When aerobic granular sludge is applied for industrial wastewater treatment,
      different soluble substrates can be present. For stable granular sludge formation
      on volatile fatty acids (e.g. acetate), production of storage polymers under
      anaerobic feeding conditions has been shown to be important. This prevents direct
      aerobic growth on readily available chemical oxygen demand (COD), which is
      thought to result in unstable granule formation. Here, we investigate the impact
      of acetate, methanol, butanol, propanol, propionaldehyde, and valeraldehyde on
      granular sludge formation at 35  degrees C. Methanogenic archaea, growing on
      methanol, were present in the aerobic granular sludge system. Methanol was
      completely converted to methane and carbon dioxide by the methanogenic archaeum
      Methanomethylovorans uponensis during the 1-h anaerobic feeding period, despite
      the relative high dissolved oxygen concentration (3.5 mg O2 L(-1)) during the
      subsequent 2-h aeration period. Propionaldehyde and valeraldehyde were fully
      disproportionated anaerobically into their corresponding carboxylic acids and
      alcohols. The organic acids produced were converted to storage polymers, while
      the alcohols (produced and from influent) were absorbed onto the granular sludge
      matrix and converted aerobically. Our observations show that easy biodegradable
      substrates not converted anaerobically into storage polymers could lead to
      unstable granular sludge formation. However, when the easy biodegradable COD is
      absorbed in the granules and/or when the substrate is converted by relatively
      slow growing bacteria in the aerobic period, stable granulation can occur.

PMID- 25616529
TI  - Principles, techniques, and applications of biocatalyst immobilization for
      industrial application.
AB  - Immobilization is one of the most effective and powerful tools used in industry,
      which has been studied and improved since the last century. Various
      immobilization techniques and support materials have been used on both laboratory
      and industrial scale. Each immobilization technique is applicable for a specific
      production mostly depending on the cost and sensibility of process. Compared to
      free biocatalyst systems, immobilization techniques often offer better stability,
      increased activity and selectivity, higher resistance, improved separation and
      purification, reuse of enzymes, and consequently more efficient process.
      Recently, many reviews have been published about immobilization systems; however,
      most of them have focused on a specific application or not emphasized in details.
      This review focuses on most commonly used techniques in industry with many recent
      applications including using bioreactor systems for industrial production. It is
      also aimed to emphasize the advantages and disadvantages of the immobilization
      techniques and how these systems improve process productivity compared to non
      immobilized systems. 

PMID- 25616523
TI  - Oxidative Stress in Alzheimer's Disease: Should We Keep Trying Antioxidant
      Therapies?
AB  - The risk of chronic diseases such as Alzheimer's disease is growing as a result
      of the continuous increasing average life span of the world population, a
      syndrome characterized by the presence of intraneural neurofibrillary tangles and
      senile plaques composed mainly by beta-amyloid protein, changes that may cause a
      number of progressive disorders in the elderly, causing, in its most advanced
      stage, difficulty in performing normal daily activities, among other
      manifestations. Therefore, it is important to understand the underlying
      pathogenic mechanisms of this syndrome. Nevertheless, despite intensive effort to
      access the physiopathological pathways of the disease, it remains poorly
      understood. In that context, some hypotheses have arisen, including the recent
      oxidative stress hypothesis, theory supported by the involvement of oxidative
      stress in aging, and the vulnerability of neurons to oxidative attack. In the
      present revision, oxidative changes and redox mechanisms in Alzheimer's disease
      will be further stressed, as well as the grounds for antioxidant supplementation
      as adjuvant therapy for the disease will be addressed. 

PMID- 25616530
TI  - Emergence of NDM-1-producing Acinetobacter pittii in Brazil.

PMID- 25616531
TI  - Melanocortin MC4 receptor agonists alleviate brain damage in abdominal
      compartment syndrome in the rat.
AB  - Intra-abdominal hypertension (IAH) is accompanied by high morbidity and mortality
      in surgical departments and ICUs. However, its specific pathophysiology is
      unclear. IAH not only leads to intra-abdominal tissue damage but also causes
      dysfunction in distal organs, such as the brain. In this study, we explore the
      protective effects of melanocortin 4 receptor agonists in IAH-induced brain
      injury. The IAH rat models were induced by hemorrhagic shock/resuscitation (with
      the mean arterial pressure (MAP) maintained at 30 mm Hg for 90 min followed by
      the reinfusion of the withdrawn blood with lactated Ringer's solution). Then, air
      was injected into the peritoneal cavity of the rats to maintain an intra
      abdominal pressure of 20 mm Hg for 4 h. The effects of the melanocortin 4
      receptor agonist RO27-3225 in alleviating the rats' IAH brain injuries were
      observed, which indicated that RO27-3225 could reduce brain edema, the
      expressions of the IL-1beta and TNF-alpha inflammatory cytokines, the blood-brain
      barrier's permeability and the aquaporin4 (AQP4) and matrix metalloproteinase 9
      (MMP9) levels. Moreover, the nicotinic acetylcholine receptor antagonist
      chlorisondamine and the selective melanocortin 4 receptor antagonist HS024 can
      negate the protective effects of the RO27-3225. The MC4R agonist can effectively
      reduce the intracerebral proinflammatory cytokine gene expression and alleviate
      the brain injury caused by blood-brain barrier damage following IAH.

PMID- 25616532
TI  - Effects of oil dispersant on solubilization, sorption and desorption of
      polycyclic aromatic hydrocarbons in sediment-seawater systems.
AB  - This work investigated effects of a prototype oil dispersant on solubilization,
      sorption and desorption of three model PAHs in sediment-seawater systems.
      Increasing dispersant dosage linearly enhanced solubility for all PAHs.
      Conversely, the dispersant enhanced the sediment uptake of the PAHs, and induced
      significant desorption hysteresis. Such contrasting effects (adsolubilization vs.
      solubilization) of dispersant were found dependent of the dispersant
      concentration and PAH hydrophobicity. The dual-mode models adequately simulated
      the sorption kinetics and isotherms, and quantified dispersant-enhanced PAH
      uptake. Sorption of naphthalene and 1-methylnaphthalene by sediment positively
      correlated with uptake of the dispersant, while sorption of pyrene dropped
      sharply when the dispersant exceeded its critical micelle concentration (CMC).
      The deepwater conditions diminished the dispersant effects on solubilization, but
      enhanced uptake of the PAHs, albeit sorption of the dispersant was lowered. The
      information may aid in understanding roles of dispersants on distribution, fate
      and transport of petroleum PAHs in marine systems. 

PMID- 25616533
TI  - Usefulness of the CHA2DS2VASc score to predict postoperative stroke in patients
      having cardiac surgery independent of atrial fibrillation.
AB  - Despite its association with cardioembolic stroke, atrial fibrillation (AF)
      appears to be inconsistent as a risk factor for postoperative strokes in patients
      who underwent cardiac surgery. Furthermore, the relation between AF and the
      CHA2DS2VASc score has not been definitively established with respect to
      postoperative stroke. We retrospectively analyzed the records of all cardiac
      surgery performed at our institution between January 2008 and July 2013. Baseline
      characteristics, operative data, and postoperative outcomes were compared in
      patients who developed stroke with those who did not. Previously recognized
      stroke risk factors, including AF, were analyzed along with the CHADS2 and
      CHA2DS2VASc scores. A total of 3,492 consecutive patients were identified, of
      which 2,077 (60%) underwent valve surgery, 915 (26%) had coronary artery bypass
      grafting, 399 (11%) underwent combined coronary artery bypass grafting and valve
      procedures, and 101 (3%) had other cardiac operations. Postoperative ischemic
      strokes occurred in 44 patients (1.2%). The development of a stroke was
      associated with older age (74 +/- 12 vs 69 +/- 12, p = 0.008), preoperative
      antiplatelet medication use (38.6% vs 24.5%, p = 0.043), congestive heart failure
      (37% vs 20%, p = 0.002), and greater CHADS2 (2.48 +/- 1.3 vs 1.98 +/- 1.1, p =
      0.015) and CHA2DS2VASc scores (4.2 +/- 1.8 vs 3.4 +/- 1.6, p = 0.002).
      Multivariable analysis demonstrated that the CHA2DS2VASc score was the only
      independent predictor of postoperative strokes (odds ratio 1.25; 95% confidence
      interval 1.05 to 1.5, p = 0.014). In conclusion, the CHA2DS2VASc score appears to
      predict postoperative strokes independent of the presence of AF.

PMID- 25616534
TI  - Usefulness of insulin like growth factor 1 as a marker of heart failure in
      children and young adults after the Fontan palliation procedure.
AB  - Growth hormone and its mediator, insulinlike growth factor 1 (IGF-1), are key
      determinants of growth in children and young adults. As patients with Fontan
      physiology often experience diminished longitudinal growth, we sought to describe
      IGF-1 levels in this population and to identify factors associated with IGF-1
      deficiency. Forty-one Fontan subjects >=5 years were evaluated in this cross
      sectional study. Age- and gender-specific height Z scores were generated using
      national data. Laboratory testing included IGF-1 and brain natriuretic peptide
      (BNP) levels. IGF-1 levels were converted to age-, gender-, and Tanner stage
      specific Z scores. BNP levels were log transformed to achieve a normal
      distribution (log-BNP). Medical records were reviewed for pertinent clinical
      variables. Predictors of IGF-1 Z score were assessed through the Student t test
      and Pearson's correlation. Median age was 11.1 years (range 5.1 to 33.5 years),
      and time from Fontan was 8.2 years (1.1 to 26.7). Mean height Z score was -0.2 +/
      0.9 with a mean IGF-1 Z score of -0.1 +/- 1.3. There was no association between
      IGF-1 Z score and height Z score. Longer interval since Fontan (R = -0.32, p =
      0.04), higher log-BNP (R = -0.40; p = 0.01), and lower indexed systemic flow on
      cardiac magnetic resonance (R = 0.55, p = 0.02) were associated with lower IGF-1
      Z scores. In conclusion, in this cohort with Fontan physiology, higher BNP and
      lower systemic flow were associated with lower IGF-1 Z score. Longitudinal
      studies are needed to determine if these relations represent a mechanistic
      explanation for diminished growth in children with this physiology and with other
      forms of congenital heart disease.

PMID- 25616535
TI  - Bedside physical examination is not obsolete.

PMID- 25616536
TI  - Coronary artery calcium and exercise electrocardiogram as predictors of coronary
      events in asymptomatic adults.
AB  - Early identification of patients at risk for coronary heart disease is crucial to
      formulate effective preventive strategies. The elevated risk of coronary artery
      calcium (CAC) for coronary heart disease is well established. Our aim was to
      estimate the relative risk of abnormal exercise electrocardiography (Ex ECG) in
      the presence of CAC. During the year 2001, 566 asymptomatic subjects performed a
      treadmill exercise test and consented to perform an unenhanced computed
      tomography to assess CAC. Patients were followed until December 2012. The
      relative risk for coronary events (acute myocardial infarction, hospitalization
      for unstable angina or coronary catheterization that resulted in angioplasty or
      coronary artery bypass surgery), of abnormal Ex ECG and presence of CAC were
      analyzed. An abnormal Ex ECG was found in 71 subjects (12.5%), and CAC was found
      in 286 subjects (50.5%). During a mean follow-up of 6.5 +/- 3.3 years, 35
      subjects experienced a first coronary event. In those without CAC, the rate of
      coronary events was low (4 of 280; 1.4%) regardless of the Ex ECG results.
      Subjects with both CAC and abnormal Ex ECG had the highest rate of coronary
      events (13 of 39; 33%). The adjusted hazard ratio for coronary events, in
      subjects with CAC, was 5.16 (95% confidence interval 2.52 to 10.60) in those with
      abnormal Ex ECG compared with those with normal Ex ECG. In conclusion, in
      subjects with CAC, further risk stratification can be achieved by an Ex ECG,
      whereas in those without CAC, an Ex ECG has less additional value in predicting
      coronary events.

PMID- 25616537
TI  - Spacers in radiotherapy treatment of prostate cancer: is reduction of toxicity
      cost-effective?
AB  - BACKGROUND AND PURPOSE: To compare the cost-effectiveness of treating prostate
      cancer patients with intensity-modulated radiation therapy and a spacer (IMRT+S)
      versus IMRT-only without a spacer (IMRT-O). MATERIALS AND METHODS: A decision
      analytic Markov model was constructed to examine the effect of late rectal
      toxicity and compare the costs and quality-adjusted Life Years (QALYs) of IMRT-O
      and IMRT+S. The main assumption of this modeling study was that disease
      progression, genito-urinary toxicity and survival were equal for both
      comparators. RESULTS: For all patients, IMRT+S revealed a lower toxicity than
      IMRT-O. Treatment follow-up and toxicity costs for IMRT-O and IMRT+S amounted to
      ?1604 and ?1444, respectively, thus saving ?160 on the complication costs at an
      extra charge of ?1700 for the spacer in IMRT+S. The QALYs yielded for IMRT-O and
      IMRT+S were 3.542 and 3.570, respectively. This results in an incremental cost
      effectiveness ratio (ICER) of ?55,880 per QALY gained. For a ceiling ratio of
      ?80,000, IMRT+S had a 77% probability of being cost-effective. CONCLUSION: IMRT+S
      is cost-effective compared to IMRT-O based on its potential to reduce
      radiotherapy-related toxicity.

PMID- 25616538
TI  - Medicine is a science of uncertainty and an art of probability (Sir W. Osler).

PMID- 25616539
TI  - Predictive value of (18)F-FAZA PET imaging for guiding the association of
      radiotherapy with nimorazole: a preclinical study.
AB  - PURPOSE: To assess the predictive value of hypoxia imaging by (18)F-FAZA PET in
      identifying tumors that may benefit from radiotherapy combined with nimorazole, a
      hypoxic radiosensitizer. MATERIAL AND METHODS: Rats of two tumor models
      (Rhabdomyosarcoma and 9L-glioma) were divided into two treated groups:
      radiotherapy (RT) alone or RT plus nimorazole. (18)F-FAZA PET images were
      obtained to evaluate tumor hypoxia before the treatment. Treatment outcome was
      assessed through the tumor growth time assay, defined as the time required for
      tumor to grow to 1.5 times its size before irradiation. RESULTS: For
      rhabdomyosarcomas, the benefit of adding nimorazole to RT was not significant
      when considering all tumors. When stratifying into more and less hypoxic tumors
      according to the median (18)F-FAZA T/B ratio, we found that the combined
      treatment significantly improved the response of the "more hypoxic" subgroup,
      while there was no significant difference in the tumor growth time between the
      two treatment modalities for the "less hypoxic" subgroup. For 9L-gliomas, a clear
      benefit was demonstrated for the group receiving RT+nimorazole. However, the
      individual responses within the RT+nimorazole group were highly variable and
      independent of the (18)F-FAZA uptake. CONCLUSIONS: (18)F-FAZA PET may be useful
      to guide hypoxia-directed RT using nimorazole as radiosensitizer. It identified a
      subgroup of more hypoxic tumors (displaying T/B ratio>2.72) that would benefit
      from this combined treatment. Nevertheless, the predictive power was limited to
      rhabdomyosarcomas and ineffective for 9L-gliomas.

PMID- 25616540
TI  - In Silico Predictions of Human Skin Permeability using Nonlinear Quantitative
      Structure-Property Relationship Models.
AB  - PURPOSE: Predicting human skin permeability of chemical compounds accurately and
      efficiently is useful for developing dermatological medicines and cosmetics.
      However, previous work have two problems; 1) quality of databases used, and 2)
      methods for prediction models. In this paper, we attempt to solve these two
      problems. METHODS: We first compile, by carefully screening from the literature,
      a novel dataset of chemical compounds with permeability coefficients, measured
      under consistent experimental conditions. We then apply machine learning
      techniques such as support vector regression (SVR) and random forest (RF) to our
      database to develop prediction models. Molecular descriptors are fully
      computationally obtained, and greedy stepwise selection is employed for
      descriptor selection. Prediction models are internally and externally validated.
      RESULTS: We generated an original, new database on human skin permeability of 211
      different compounds from aqueous donors. Nonlinear SVR achieved the best
      performance among linear SVR, nonlinear SVR, and RF. The determination
      coefficient, root mean square error, and mean absolute error of nonlinear SVR in
      external validation were 0.910, 0.342, and 0.282, respectively. CONCLUSIONS: We
      provided one of the largest datasets with purely experimental log kp and
      developed reliable and accurate prediction models for screening active
      ingredients and seeking unsynthesized compounds of dermatological medicines and
      cosmetics.

PMID- 25616541
TI  - [Evaluation of the postoperative systemic response in congenital heart defects].

PMID- 25616542
TI  - [Long-term follow up of childhood cancer survivors in the Murcia Region:
      preferences and attitudes of Primary Care professionals].
AB  - OBJECTIVE: To assess attitudes, beliefs and knowledge of primary medical care
      professionals as regards the follow-up of Childhood Cancer Survivors (CCS) and
      the introduction of a Long-Term Follow-Up Program for Childhood Cancer Survivors
      in the Region of Murcia (PLASESCAP-MUR). MATERIAL AND METHODS: Descriptive cross
      sectional study using a structured, self-administered questionnaire. These
      questionnaires were sent to all primary medical care professionals in Murcia
      Health District 1. RESULTS: Response rate of 58% (100/172), with 71% and 22%
      being family physicians and pediatricians, respectively, of whom 49% provided
      medical care to a CCS in the last 5 years, with 84% reporting that they never or
      rarely received a detailed report of overall assessment of the survivor. More
      than 75% found that access to detailed follow-up information was quite or very
      useful; 95% prefer to consult experts when providing medical care to survivors,
      and 80% believe that improving the quality of the environment may decrease the
      morbidity and mortality of the survivors. A statistically significant
      relationship was found between the length of practicing medicine and the
      perception of the importance of environmental factors. CONCLUSIONS: It seems to
      be important to increase the training of primary care professionals for the long
      term follow-up of CCS, as well as having the detailed information through a
      personalized long-term follow-up of each survivor. PLASESCAP-MUR offers an
      integrated follow-up to CCS in a model of shared care between Long Term
      Monitoring Units and Primary Care Units.

PMID- 25616543
TI  - [Clinical and molecular diagnostics of a cartilage-hair hypoplasia: Two new
      cases].

PMID- 25616544
TI  - [Forms of clinical presentation of hypothalamic hamartoma].

PMID- 25616545
TI  - [Importance of integrated care processes on quality accreditation of pediatric
      clinic management units].

PMID- 25616546
TI  - [Vitamin D in the newborn: An unusual cause of irritability].

PMID- 25616547
TI  - [Multifocal musculoskeletal myofibromatosis].

PMID- 25616548
TI  - Track-event theory of cell survival with second-order repair.
AB  - When fractionation schemes for hypofractionation and stereotactic body
      radiotherapy are considered, a reliable cell survival model at high dose is
      needed for calculating doses of similar biological effectiveness. In this work, a
      simple model for cell survival which is valid also at high dose is developed from
      Poisson statistics. It is assumed that a cell is killed by an event that is
      defined by two double-strand breaks on the same or different chromosomes. Two
      different mechanisms can produce events. A one-track event is always represented
      by two simultaneous double-strand breaks. A two-track event results in one double
      strand break. Therefore, at least two two-track events on the same or different
      chromosomes are necessary to produce an event. It is assumed that two double
      strand breaks can be repaired with a certain repair probability. Both the one
      track events and the two-track events are statistically independent. From the
      stochastic nature of cell killing which is described by the Poisson distribution,
      the cell survival probability was derived. The model was fitted to experimental
      data. It was shown that a solution based on Poisson statistics exists for cell
      survival. It exhibits exponential cell survival at high dose and a finite
      gradient of cell survival at vanishing dose, which is in agreement with
      experimental cell studies. The model fits the experimental data as well as the LQ
      model and is based on two free parameters. It was shown that cell survival can be
      described with a simple analytical formula on the basis of Poisson statistics.
      This solution represents in the limit of large dose the typical exponential
      behavior and predicts cell survival as well as the LQ model. 

PMID- 25616549
TI  - [Two years of open access].

PMID- 25616550
TI  - [25 Years of health & communication].

PMID- 25616551
TI  - Probiotics in addition to antibiotics for the treatment of acute tonsillitis: a
      randomized, placebo-controlled study.
AB  - Probiotics are live microorganisms which, when administered in adequate amounts,
      confer a health benefit on the host. The probiotic Streptococcus salivarius has
      been shown to be effective in reducing the frequency of recurrent pharyngeal
      infections in children and adult populations. However, probiotics have not yet
      been evaluated in the treatment of acute pharyngotonsillitis in adults. We aimed
      to examine whether the addition of S. salivarius probiotics to the routine
      therapy of acute pharyngotonsillitis in adult patients may shorten disease
      duration and reduce symptom severity. This study was a prospective, randomized,
      placebo-controlled, double-blinded study comparing treatment with probiotics to
      placebo in addition to antibiotics in patients who were hospitalized with severe
      pharyngotonsillitis. Laboratory results, pain levels, body temperature, and daily
      volume of fluids consumed were recorded for both groups. Sixty participants were
      recruited, 30 for each group. No statistically significant differences between
      the two groups were observed regarding any of the major clinical and laboratory
      parameters examined. Supplement probiotic treatment with S. salivarius in
      patients with acute pharyngotonsillitis treated with penicillin is ineffective in
      relation to the parameters examined in this study and we cannot, therefore,
      recommend the use of S. salivarius during active pharyngotonsillar infection
      treated with penicillin. 

PMID- 25616552
TI  - Comparison of BD Max Cdiff and GenomEra C. difficile molecular assays for
      detection of toxigenic Clostridium difficile from stools in conventional sample
      containers and in FecalSwabs.
AB  - In this study, the usability and performance of GenomEraTM C. difficile and BD
      MaxTM Cdiff nucleic acid amplification tests (NAATs) for the detection of
      toxigenic Clostridium difficile were investigated in comparison with toxigenic
      culture and C. difficile toxin A- and toxin B-detecting immunochromatographic
      antigen (IA) test, the Tox A/B QuikChek(r). In total, 302 faecal specimens were
      collected, 113 of which were in parallel to conventional sample containers and
      FecalSwab liquid-based microbiology (LBM) tubes. Seventy-nine specimens were
      considered true-positives for toxigenic C. difficile. The sensitivity and
      specificity were 97.5 % and 99.6 % and 93.7 % and 98.7 % for the GenomEra and BD
      Max assays respectively. Toxigenic culture and Tox A/B QuikChek had sensitivity
      and specificity of 91.1 % and 100 % and 34.2 % and 100 % respectively. Hands-on
      time for analysing 1 to 24 specimens using NAATs was 1 to 15 min. The rate of PCR
      inhibition was 0 % for both NAATs with faeces in LBM tubes, while with faeces in
      conventional sample containers the respective inhibition rates were 5.3 % and 4.4
      % for the GenomEra and the BD Max assays. The NAATs demonstrated an excellent
      analytical performance, reducing significantly the overall workload of laboratory
      personnel compared with culture and IA test. 

PMID- 25616553
TI  - Detection of proline-rich proteins for the identification of saliva by enzyme
      linked immunosorbent assay.
AB  - Saliva is one of the most common body fluids found at a crime scene. Therefore,
      identifying saliva is important in forensic science. However, the current protein
      marker assays used to identify saliva are not sufficiently specific. Although
      proline-rich proteins (PRPs) are highly specific for saliva, their forensic
      potential has not yet been investigated. In this study, we developed enzyme
      linked immunosorbent assays (ELISAs) to detect acidic salivary PRP HaeIII
      subfamily 1/2 (PRH1/2) and basic salivary PRP 2 (PRB2). The specificity,
      sensitivity, and efficiency of the ELISAs for PRH1/2 and PRB2 were compared with
      those of the ELISA for statherin (STATH), a known protein marker for saliva. The
      levels of PRH1/2 were significantly higher in saliva and saliva stains than in
      other body fluids (nasal secretions, urine, semen, vaginal fluid, blood, and
      sweat). PRB2 and STATH were detected in both nasal secretions and saliva. The
      PRH1/2 ELISA showed sensitivity similar to that of STATH ELISA. The detection
      rate of PRH1/2 ELISA was almost similar to that of STATH ELISA, followed by the
      ELISA for PRB2. The PRH1/2 ELISA had higher specificity for saliva than STATH
      ELISA. Therefore, the PRH1/2 ELISA has potential as a method to identify saliva
      for forensic investigation. 

PMID- 25616554
TI  - The effects of temperature, organic matter and time-dependency on rheological
      properties of dry anaerobic digested swine manure.
AB  - An efficient way to avoid the pollution of swine wastewater is the application of
      dry anaerobic digestion, which needs rheological parameter for stirring and pipe
      designing. The rheological properties of this kind of sludge have been studied
      for many decades, yet their effects only solid concentration has been
      investigated widely. In this paper, the influences of temperature, organic and
      time-dependency on the efficiency of anaerobic digested swine manure were
      studied. The viscosity decreased with temperature arranged from 10 to 60  degrees
      C which caused increase in protein from 7.18 to 8.49 g/kg. 60  degrees C can make
      the digested swine manure with TS from 16.6% to 21.5% reach to the same rheology
      state. The added peptone decreased the viscosity because of its function of water
      reducing admixture and air entraining mixture. Time-dependent experiment showed
      the decrease of shear stress over time. The first and the second yield stress of
      dry anaerobic digested swine manure were evaluated through time-dependent model.

PMID- 25616556
TI  - Asymmetric morphology of the cells comprising the inner and outer bending sides
      of the murine duodenojejunal flexure.
AB  - The asymmetric shape of component cells determines the asymmetric features of
      developing organs. Here, we focused on the murine duodenojejunal flexure (DJF),
      which bends without affecting the mesentery, and analyzed the morphological
      asymmetries of the mucosal epithelium and gut wall cells between the inner and
      outer bending sides at embryonic days 10.75-11.75. In the mucosal epithelium, the
      cell shape and the expression of epithelial markers (Cdx2, E-cadherin) showed no
      differences between the two DJF sides. In contrast, the gut wall cells comprising
      the inner and outer sides of the DJF were elongated along the inner-outer axis
      and perpendicular to this axis, respectively. Furthermore, the gut wall cells in
      the outer side possessed cytoplasmic processes connecting cells via adherens
      junctions, but those in the inner side were attached via adherens junctions of
      juxtaposed cell bodies and were relatively more crowded. In immunohistochemistry
      experiments, there was no remarkable difference in the positive reactions of
      markers for mesenchyme (vimentin), smooth muscle cells (alphaSMA), endothelial
      cells (LYVE-1, CD34), and undifferentiated neurons (Sox10) between the DJF sides.
      Interestingly, Tuj1-positive cells, indicating differentiated neurons, were
      observed in the middle layer of the gut wall, and these cells were significantly
      more abundant and tended to be larger in the inner side than in the outer side of
      the DJF. In conclusion, we clarified the asymmetries of gut wall cell morphology
      and neural differentiation between the inner and outer sides of the DJF. These
      characteristics of the developing murine DJF indicate its asymmetric formation.

PMID- 25616555
TI  - Scaffolding protein GOPC regulates tight junction structure.
AB  - GOPC (FIG/PIST/CAL) is a PDZ-domain scaffolding protein that regulates the
      trafficking of a wide array of proteins, including small GTPases, receptors and
      cell surface molecules such as cadherin 23 and cystic fibrosis transmembrane
      regulator. In Madin-Darby canine kidney (MDCK) cells, we find that GOPC localizes
      to the trans-Golgi network (TGN) but not to the cis- or trans-Golgi cisternae.
      Colocalization occurs with the early endosome Rab GTPase Rab5 and a TGN/endosome
      marker Rab14 but not with Rab11, a marker of recycling endosomes. No localization
      of GOPC was detected to the lateral membranes or tight junctions. Knockdown of
      GOPC in MDCK cells results in decreased transepithelial resistance and increased
      paracellular flux. This might be attributable to the compromised trafficking of
      tight junction components from the TGN, as GOPC-knockdown cells have decreased
      lateral labeling of the tight junction protein claudin-1 and decreased protein
      levels of claudin-2. GOPC might mediate the trafficking of newly synthesized
      tight junction proteins from the TGN to the cell surface or the recycling of
      these proteins from specialized endosomal compartments. 

PMID- 25616557
TI  - Connexins and skin disease: insights into the role of beta connexins in skin
      homeostasis.
AB  - Cell-to-cell communication triggered by connexin channels plays a central role in
      maintaining epidermal homeostasis. Here, we discuss the role of the beta connexin
      subgroup, where site-specific mutations in at least 4 of these proteins lead to
      distinctive non-inflammatory and inflammatory hyperproliferative epidermal
      disorders. Recent advances in the molecular pathways evoked and correlation with
      clinical outcome are discussed. The latest data provide increasing evidence that
      connexins in the epidermis are sensors to environmental stress and that targeting
      aberrant hemichannel activity holds significant therapeutic potential for
      inflammatory skin disorders. 

PMID- 25616559
TI  - Abstracts of the Irish Society of Gastroenterology Summer Meeting, June 12-13,
      2014, Kildare, Ireland.

PMID- 25616560
TI  - The imperative for patient-centred research to develop better quality services in
      rare diseases.

PMID- 25616558
TI  - Quality of oral anticoagulation with phenprocoumon in regular medical care and
      its potential for improvement in a telemedicine-based coagulation service-
      results from the prospective, multi-center, observational cohort study
      thrombEVAL.
AB  - BACKGROUND: The majority of studies on quality of oral anticoagulation (OAC)
      therapy with vitamin K-antagonists are performed with short-acting warfarin. Data
      on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy
      and is considered to enable more stable therapy adjustment, are scarce. In this
      study, we aimed to assess quality of OAC therapy with phenprocoumon in regular
      medical care and to evaluate its potential for optimization in a telemedicine
      based coagulation service. METHODS: In the prospective observational cohort study
      program thrombEVAL we investigated 2,011 patients from regular medical care in a
      multi-center cohort study and 760 patients from a telemedicine-based coagulation
      service in a single-center cohort study. Data were obtained from self-reported
      data, computer-assisted personal interviews, and laboratory measurements
      according to standard operating procedures with detailed quality control. Time in
      therapeutic range (TTR) was calculated by linear interpolation method to assess
      quality of OAC therapy. Study monitoring was carried out by an independent
      institution. RESULTS: Overall, 15,377 treatment years and 48,955 international
      normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as
      measured by median TTR, was 66.3% (interquartile range (IQR) 47.8/81.9) in
      regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P
      <0.001). Stable anticoagulation control within therapeutic range was achieved in
      63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as
      compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR
      65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients
      with pretreatment in regular medical care showed an improvement of the TTR from
      66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation
      service. Treatment in the coagulation service contributed to an optimization of
      the profile of time outside therapeutic range, a 2.2-fold increase of stabile INR
      adjustment and a significant decrease in TTR variability by 36% (P <0.001).
      CONCLUSIONS: Quality of anticoagulation with phenprocoumon was comparably high in
      this real-world sample of regular medical care. Treatment in a telemedicine-based
      coagulation service substantially improved quality of OAC therapy with regard to
      TTR level, frequency of stable anticoagulation control, and TTR variability.
      TRIAL REGISTRATION: ClinicalTrials.gov, unique identifier NCT01809015, March 8,
      2013.

PMID- 25616561
TI  - Environmental and DNA repair risk factors for breast cancer in South China.
AB  - PURPOSE: The incidence of breast cancer (BC) in China has been rapidly
      increasing. We hypothesize that China-specific risk factors, both life-style and
      inherent ones, contribute to the problem. METHOD: We have conducted an
      epidemiology and functional DNA repair investigation to identify risk factors for
      the development of BC in Shantou, China. RESULTS: Our survey of 372 patients and
      419 matched normal controls confirmed the significant risk from many universal
      factors: high BMI, low education level, low fruit intake and sedate lifestyle.
      Significant risk factors can be organized into endogenous ones (low education and
      cooking with lard instead of vegetable oil) and externally-introduced ones
      (sedate life-style and cigarette smoking). We also found highly significant risk
      from passive exposure to cigarette smoke. Using the Challenge-Comet assay and
      blood samples from 57 patients who did not inherit the tumor suppressor BRCA gene
      mutations and 62 matched normal controls; we showed that reduced functional DNA
      repair capacity was a significant risk factor. In addition, the reduced repair
      capacity was associated with lymph node metastasis, and with tumors that had
      negative ER receptor and over-expression of Her-2. CONCLUSION: Our study
      indicates that combined externally-introduced and endogenous life-style factors
      were involved with the increased incidence of BC in China. We also showed, for
      the first time, that inherent deficiency in DNA repair function was a significant
      risk factor for BC. The inherent deficiency can interact with other risk factors
      to significantly increase risk for BC. In addition, the reduced repair capacity
      was associated with certain clinical features that are indicative of poor
      prognosis. In this context, it is possible to integrate DNA repair capacity
      knowledge in promoting prevention of BC and in enhancing personalized therapeutic
      protocols.

PMID- 25616562
TI  - One size does not fit all: HIV testing preferences differ among high-risk groups
      in Northern Tanzania.
AB  - In order to maximize the effectiveness of "Seek, Test, and Treat" strategies for
      curbing the HIV epidemic, new approaches are needed to increase the uptake of HIV
      testing services, particularly among high-risk groups. Low HIV testing rates
      among such groups suggest that current testing services may not align well with
      the testing preferences of these populations. Female bar workers and male
      mountain porters have been identified as two important high-risk groups in the
      Kilimanjaro Region of Tanzania. We used conventional survey methods and a
      discrete choice experiment (DCE), a preference elicitation method increasingly
      applied by economists and policy-makers to inform health policy and services, to
      analyze trade-offs made by individuals and quantify preferences for HIV testing
      services. Bivariate descriptive statistics were used to analyze differences in
      survey responses across groups. Compared to 486 randomly selected community
      members, 162 female bar workers and 194 male Kilimanjaro porters reported 2-3
      times as many lifetime sexual partners (p < 0.001), but similar numbers of
      lifetime HIV tests (median 1-2 across all groups). For the DCE, participants'
      stated choices across 12,978 hypothetical HIV testing scenarios (422 female and
      299 male participants * 9 choice tasks * 2 alternatives) were analyzed using
      gender-specific mixed logit models. Direct assessments and the DCE data
      demonstrated that barworkers were less likely to prefer home testing and were
      more concerned about disclosure issues compared with their community
      counterparts. Male porters preferred testing in venues where antiretroviral
      therapy was readily available. Both high-risk groups were less averse to
      traveling longer distances to test compared to their community counterparts.
      These results expose systematic differences in HIV testing preferences across
      high-risk populations compared to their community peers. Tailoring testing
      options to the preferences of high-risk populations should be evaluated as a
      means of improving uptake of testing in these populations. 

PMID- 25616563
TI  - Botulinum toxin is efficient to treat obstructive symptoms in children with
      Hirschsprung disease.
AB  - BACKGROUND: Obstructive symptoms are common after pull-through for Hirschsprung
      disease. Botulinum toxin injection treatment may improve the bowel function if
      internal sphincter achalasia is the cause of obstructive symptoms. The aim of
      this study was to review the outcome in patients treated with intrasphincteric
      botulinum toxin injections after pull-through for Hirschsprung disease. METHODS:
      The operative records were used to identify children with Hirschsprung disease
      who were treated with botulinum toxin injections at Karolinska University
      Hospital, Stockholm, Sweden, from September 2007 to November 2014. Data on age,
      sex, associated syndromes, length of aganglionic segment, age at pull-through,
      type of pull-through, age at first botulinum toxin injection, indication for
      botulinum toxin injection, and effect of first botulinum toxin injection were
      retrieved from the case records. Bowel function at last follow-up visit or
      telephone contact was recorded. RESULTS: Nineteen patients were identified. All
      had biopsy-verified Hirschsprung disease. Eighteen (15 males and 3 females)
      children had undergone intrasphincteric botulinum toxin injection treatment for
      obstructive symptoms after pull-through, which was done at 127 (18-538) days of
      age. Four children had total colonic aganglionosis. The first botulinum toxin
      injection was given at 2.4 (0.53-6.9) years of age. Thirteen children (72 %) had
      a good response to the first injection treatment. The children underwent 3 (1-13)
      injection treatments. At follow-up four patients had improved and did not need
      treatment for obstruction, four were scheduled for further botulinum toxin
      injections, eight had persistent obstructive symptoms treated with laxatives or
      enemas, and two children had an ileostomy. CONCLUSION: Botulinum toxin injection
      treatment improves the obstructive symptoms in children after pull-through for
      Hirschsprung disease. The effect is reversible and a majority of patients need
      repeat injections. When injection treatment is not repeated, a large proportion
      of children need laxatives or enemas due to recurrent symptoms.

PMID- 25616564
TI  - Management of tracheobronchial obstruction in infants using metallic stents: long
      term outcome.
AB  - INTRODUCTION: Tracheobronchial obstruction, although uncommon in the pediatric
      age group, remains a challenging problem. We review the long-term outcome of
      endoscopic metallic stenting in infants with tracheobronchial obstruction.
      MATERIALS AND METHODS: Medical records of all pediatric surgical patients who
      underwent tracheobronchial metallic stenting in our center were reviewed
      retrospectively from 1996 to 2014. Patients' demographic data, including
      etiology, associated anomalies and nature of obstruction were reviewed. Outcome
      measures include complications such as re-stenosis, granulation tissue, stent
      migration, fractured stent, maximal tracheal diameter achieved, weaning of
      ventilator and growth at interval follow-up. RESULTS: Twelve balloon-expandable
      metallic stents were placed in the trachea (n = 10) and/or bronchi (n = 2) of 5
      patients with a median age of 13 months (range 5-30 months). Etiology of the
      airway obstruction included congenital tracheal stenosis (n = 4), giant cervical
      and superior mediastinal lymphatic malformation with tracheobronchomalacia (n =
      1). Seven complications were reported (3 patients developed granulation tissue, 2
      patients had re-stenosis, 1 stent migrated, 1 stent fractured). All patients
      survived and were in good condition with a median follow-up of 16 years (range 11
      18 years). Three patients weaned off ventilator and oxygen. CONCLUSIONS:
      Endoscopic stenting with metallic stent has satisfactory long-term outcome in
      treating infants with tracheobronchial obstruction.

PMID- 25616566
TI  - Nanomaterial applications in multiple sclerosis inflamed brain.
AB  - In the last years scientific progress in nanomaterials, where size and shape make
      the difference, has increased their utilization in medicine with the development
      of a promising new translational science: nanomedicine. Due to their surface and
      core biophysical properties, nanomaterials hold the promise for medical
      applications in central nervous system (CNS) diseases: inflammatory, degenerative
      and tumors. The present review is focused on nanomaterials at the neuro-immune
      interface, evaluating two aspects: the possible CNS inflammatory response induced
      by nanomaterials and the developments of nanomaterials to improve treatment and
      diagnosis of neuroinflammatory diseases, with a focus on multiple sclerosis (MS).
      Indeed, nanomedicine allows projecting new ways of drug delivery and novel
      techniques for CNS imaging. Despite the wide field of application in neurological
      diseases of nanomaterials, our topic here is to review the more recent
      development of nanomaterials that cross blood brain barrier (BBB) and reach
      specific target during CNS inflammatory diseases, a crucial strategy for CNS
      early diagnosis and drug delivery, indeed the main challenges of nanomedicine. 

PMID- 25616565
TI  - Metabolic Profiling and Phenotyping of Central Nervous System Diseases:
      Metabolites Bring Insights into Brain Dysfunctions.
AB  - Metabolic phenotyping corresponds to the large-scale quantitative and qualitative
      analysis of the metabolome i.e., the low-molecular weight <1 KDa fraction in
      biological samples, and provides a key opportunity to advance neurosciences.
      Proton nuclear magnetic resonance and mass spectrometry are the main analytical
      platforms used for metabolic profiling, enabling detection and quantitation of a
      wide range of compounds of particular neuro-pharmacological and physiological
      relevance, including neurotransmitters, secondary messengers, structural lipids,
      as well as their precursors, intermediates and degradation products. Metabolic
      profiling is therefore particularly indicated for the study of central nervous
      system by probing metabolic and neurochemical profiles of the healthy or diseased
      brain, in preclinical models or in human samples. In this review, we introduce
      the analytical and statistical requirements for metabolic profiling. Then, we
      focus on key studies in the field of metabolic profiling applied to the
      characterization of animal models and human samples of central nervous system
      disorders. We highlight the potential of metabolic profiling for pharmacological
      and physiological evaluation, diagnosis and drug therapy monitoring of patients
      affected by brain disorders. Finally, we discuss the current challenges in the
      field, including the development of systems biology and pharmacology strategies
      improving our understanding of metabolic signatures and mechanisms of central
      nervous system diseases. 

PMID- 25616568
TI  - Improved robust stabilization method for linear systems with interval time
      varying input delays by using Wirtinger inequality.
AB  - This paper investigates the robust stabilization problem for uncertain linear
      systems with interval time-varying delays. By constructing novel Lyapunov
      Krasovskii functionals and developing delay-partitioning approaches, some delay
      dependent stability criteria are derived based on an improved Wirtinger's
      inequality and the reciprocally convex method. The proposed methods have improved
      the stability conditions without increasing much computational complexity. A
      state feedback controller design approach is also presented based on the proposed
      criteria. Numerical examples are finally given to illustrate the effectiveness of
      the proposed method. 

PMID- 25616567
TI  - Investigation of tick-borne bacteria (Rickettsia spp., Anaplasma spp., Ehrlichia
      spp. and Borrelia spp.) in ticks collected from Andean tapirs, cattle and
      vegetation from a protected area in Ecuador.
AB  - BACKGROUND: Ixodid ticks play an important role in the transmission and ecology
      of infectious diseases. Information about the circulation of tick-borne bacteria
      in ticks is lacking in Ecuador. Our aims were to investigate the tick species
      that parasitize Andean tapirs and cattle, and those present in the vegetation
      from the buffer zone of the Antisana Ecological Reserve and Cayambe-Coca National
      Park (Ecuador), and to investigate the presence of tick-borne bacteria. METHODS:
      Tick species were identified based on morphologic and genetic criteria. Detection
      of tick-borne bacteria belonging to Rickettsia, Anaplasma, Ehrlichia and Borrelia
      genera was performed by PCRs. RESULTS: Our ticks included 91 Amblyomma
      multipunctum, 4 Amblyomma spp., 60 Rhipicephalus microplus, 5 Ixodes spp. and 1
      Ixodes boliviensis. A potential Candidatus Rickettsia species closest to
      Rickettsia monacensis and Rickettsia tamurae (designated Rickettsia sp. 12G1) was
      detected in 3 R. microplus (3/57, 5.3%). In addition, Anaplasma spp., assigned at
      least to Anaplasma phagocytophilum (or closely related genotypes) and Anaplasma
      marginale, were found in 2 A. multipunctum (2/87, 2.3%) and 13 R. microplus
      (13/57, 22.8%). CONCLUSIONS: This is the first description of Rickettsia sp. in
      ticks from Ecuador, and the analyses of sequences suggest the presence of a
      potential novel Rickettsia species. Ecuadorian ticks from Andear tapirs, cattle
      and vegetation belonging to Amblyomma and Rhipicephalus genera were infected with
      Anaplasmataceae. Ehrlichia spp. and Borrelia burgdorferi sensu lato were not
      found in any ticks.

PMID- 25616570
TI  - [Multimodal pain therapy : End of an odyssey].

PMID- 25616569
TI  - [Multimodal therapy programs for chronic pain].
AB  - Chronic pain is a common and disabling disorder with major consequences for
      patient quality of life and it is also a major economic burden to society. The
      management of chronic pain comprises a large range of different intervention
      strategies including pharmacological therapy, non-medicinal and invasive
      therapeutic options. While non-pharmacological and multimodal options are
      underused, monomodal options, especially pharmacotherapy and invasive therapies
      are overused. The effectiveness of multidisciplinary and multimodal treatment
      programs including physical and rehabilitation interventions and psychological
      treatment has been extensively studied in the last two decades. Evidence from
      randomized controlled trials demonstrates that there is low quality evidence for
      the effectiveness of exercise therapy alone, there is some evidence for the
      effectiveness of behavioral therapy and there is at least moderate evidence for
      the effectiveness of multidisciplinary and multimodal treatment and other active
      treatment reducing pain and increasing functional capacity at short and
      intermediate term. Therefore, blanket coverage with provision of adequate
      treatment programs for chronic pain as well as studies evaluating the best
      composition of treatment elements are needed. The characteristics of chronic
      pain, the necessary assessment procedures and treatment types are described. 

PMID- 25616571
TI  - Reversal of hemochromatosis by apotransferrin in non-transfused and transfused
      Hbbth3/+ (heterozygous B1/B2 globin gene deletion) mice.
AB  - Intermediate beta-thalassemia has a broad spectrum of sequelae and affected
      subjects may require occasional blood transfusions over their lifetime to correct
      anemia. Iron overload in intermediate beta-thalassemia results from a paradoxical
      intestinal absorption, iron release from macrophages and hepatocytes, and
      sporadic transfusions. Pathological iron accumulation in parenchyma is caused by
      chronic exposure to non-transferrin bound iron in plasma. The iron scavenger and
      transport protein transferrin is a potential treatment being studied for
      correction of anemia. However, transferrin may also function to prevent or reduce
      iron loading of tissues when exposure to non-transferrin bound iron increases.
      Here we evaluate the effects of apotransferrin administration on tissue iron
      loading and early tissue pathology in non-transfused and transfused Hbb(th3/+)
      mice. Mice with the Hbb(th3/+) phenotype have mild to moderate anemia and
      consistent tissue iron accumulation in the spleen, liver, kidneys and myocardium.
      Chronic apotransferrin administration resulted in normalization of the anemia.
      Furthermore, it normalized tissue iron content in the liver, kidney and heart and
      attenuated early tissue changes in non-transfused Hbb(th3/+) mice. Apotransferrin
      treatment was also found to attenuate transfusion-mediated increases in plasma
      non-transferrin bound iron and associated excess tissue iron loading. These
      therapeutic effects were associated with normalization of transferrin saturation
      and suppressed plasma non-transferrin bound iron. Apotransferrin treatment
      modulated a fundamental iron regulatory pathway, as evidenced by decreased
      erythroid Fam132b gene (erythroferrone) expression, increased liver hepcidin gene
      expression and plasma hepcidin-25 levels and consequently reduced intestinal
      ferroportin-1 in apotransferrin-treated thalassemic mice. 

PMID- 25616572
TI  - Late cardiomyopathy in childhood acute myeloid leukemia survivors: a study from
      the L.E.A. program.

PMID- 25616573
TI  - Evidence for idiotype-directed immunosurveillance is restricted to follicular
      lymphoma and attributable to somatic hypermutation.

PMID- 25616574
TI  - Hematopoiesis specific loss of Cdk2 and Cdk4 results in increased erythrocyte
      size and delayed platelet recovery following stress.
AB  - Mouse knockouts of Cdk2 and Cdk4 are individually viable whereas the double
      knockouts are embryonic lethal due to heart defects, and this precludes the
      investigation of their overlapping roles in definitive hematopoiesis. Here we use
      a conditional knockout mouse model to investigate the effect of combined loss of
      Cdk2 and Cdk4 in hematopoietic cells. Cdk2(fl/fl)Cdk4(-/-)vavCre mice are viable
      but displayed a significant increase in erythrocyte size. Cdk2(fl/fl)Cdk4(-/
      )vavCre mouse bone marrow exhibited reduced phosphorylation of the retinoblastoma
      protein and reduced expression of E2F target genes such as cyclin A2 and Cdk1.
      Erythroblasts lacking Cdk2 and Cdk4 displayed a lengthened G1 phase due to
      impaired phosphorylation of the retinoblastoma protein. Deletion of the
      retinoblastoma protein rescued the increased size displayed by erythrocytes
      lacking Cdk2 and Cdk4, indicating that the retinoblastoma/Cdk2/Cdk4 pathway
      regulates erythrocyte size. The recovery of platelet counts following a 5
      fluorouracil challenge was delayed in Cdk2(fl/fl)Cdk4(-/-)vavCre mice revealing a
      critical role for Cdk2 and Cdk4 in stress hematopoiesis. Our data indicate that
      Cdk2 and Cdk4 play important overlapping roles in homeostatic and stress
      hematopoiesis, which need to be considered when using broad-spectrum cyclin
      dependent kinase inhibitors for cancer therapy. 

PMID- 25616575
TI  - Generation of a poor prognostic chronic lymphocytic leukemia-like disease model:
      PKCalpha subversion induces up-regulation of PKCbetaII expression in B
      lymphocytes.
AB  - Overwhelming evidence identifies the microenvironment as a critical factor in the
      development and progression of chronic lymphocytic leukemia, underlining the
      importance of developing suitable translational models to study the pathogenesis
      of the disease. We previously established that stable expression of kinase dead
      protein kinase C alpha in hematopoietic progenitor cells resulted in the
      development of a chronic lymphocytic leukemia-like disease in mice. Here we
      demonstrate that this chronic lymphocytic leukemia model resembles the more
      aggressive subset of chronic lymphocytic leukemia, expressing predominantly
      unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP
      70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced
      proliferation and increased tumor load in lymphoid organs. Reduced function of
      PKCalpha leads to an up-regulation of PKCbetaII expression, which is also
      associated with a poor prognostic subset of human chronic lymphocytic leukemia
      samples. Treatment of chronic lymphocytic leukemia-like cells with the selective
      PKCbeta inhibitor enzastaurin caused cell cycle arrest and apoptosis both in
      vitro and in vivo, and a reduction in the leukemic burden in vivo. These results
      demonstrate the importance of PKCbetaII in chronic lymphocytic leukemia-like
      disease progression and suggest a role for PKCalpha subversion in creating
      permissive conditions for leukemogenesis. 

PMID- 25616576
TI  - Current outcome of HLA identical sibling versus unrelated donor transplants in
      severe aplastic anemia: an EBMT analysis.
AB  - We have analyzed 1448 patients with acquired aplastic anemia grafted between 2005
      and 2009, and compared outcome of identical sibling (n=940) versus unrelated
      donor (n=508) transplants. When compared to the latter, sibling transplants were
      less likely to be performed beyond 180 days from diagnosis (39% vs. 85%), to have
      a cytomegalovirus negative donor/recipient status (15% vs. 23%), to receive
      antithymocyte globulin in the conditioning (52% vs. 61%), and more frequently
      received marrow as a stem cell source (60% vs. 52%). Unrelated donor grafts had
      significantly more acute grade II-IV (25% vs. 13%) and significantly more chronic
      graft-versus-host disease (26% vs. 14%). In multivariate analysis, the risk of
      death of unrelated donor grafts was higher, but not significantly higher,
      compared to a sibling donor (P=0.16). The strongest negative predictor of
      survival was the use of peripheral blood as a stem cell source (P<0.00001),
      followed by an interval of diagnosis to transplant of 180 days or more
      (P=0.0005), patient age 20 years or over (P=0.0005), no antithymocyte globulin in
      the conditioning (P=0.003), and donor/recipient cytomegalovirus sero-status,
      other than negative/negative (P=0.04). In conclusion, in multivariate analysis,
      the outcome of unrelated donor transplants for acquired aplastic anemia, is
      currently not statistically inferior when compared to sibling transplants,
      although patients are at greater risk of acute and chronic graft-versus-host
      disease. The use of peripheral blood grafts remains the strongest negative
      predictor of survival. 

PMID- 25616578
TI  - Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from
      chronic lymphocytic leukemia patients by human macrophages.

PMID- 25616579
TI  - The Role of Parents' Critical Thinking About Media in Shaping Expectancies,
      Efficacy and Nutrition Behaviors for Families.
AB  - A convenience survey completed online by 137 4-H parents in Washington state
      explored their orientation toward critical thinking regarding media sources and
      content and its implications for family dietary behaviors. Parents' critical
      thinking toward media sources predicted their information efficacy about content.
      Critical thinking toward media content predicted information efficacy about
      sources, expectancies for parental mediation, and expectancies for family
      receptiveness to lower-fat dietary changes. Expectancies for receptiveness to
      dietary changes and expectancies for parental mediation predicted efficacy for
      implementing healthy dietary practices; this strongly predicted healthy dietary
      practices. Media-related critical thinking, therefore, indirectly but
      consistently affected self-reported family dietary behaviors through its effects
      on efficacy for managing media and expectancies for the family's receptiveness to
      healthy dietary changes. The results suggest parents' media literacy skills
      affect their family's dietary behavior. Health campaigns that help parents
      interpret and manage the media environment may benefit all family members. 

PMID- 25616577
TI  - Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis:
      results of a median 3-year follow-up of COMFORT-I.
AB  - In the phase III COMFORT-I study, the Janus kinase 1 (JAK1)/JAK2 inhibitor
      ruxolitinib provided significant improvements in splenomegaly, key symptoms, and
      quality-of-life measures and was associated with an overall survival benefit
      relative to placebo in patients with intermediate-2 or high-risk myelofibrosis.
      This planned analysis assessed the long-term efficacy and safety of ruxolitinib
      at a median follow-up of 149 weeks. At data cutoff, approximately 50% of patients
      originally randomized to ruxolitinib remained on treatment whereas all patients
      originally assigned to placebo had discontinued or crossed over to ruxolitinib.
      At week 144, mean spleen volume reduction was 34% with ruxolitinib. Previously
      observed improvements in quality-of-life measures were sustained with longer-term
      ruxolitinib therapy. Overall survival continued to favor ruxolitinib despite the
      majority of placebo patients crossing over to ruxolitinib [hazard ratio 0.69 (95%
      confidence interval: 0.46-1.03); P = 0.067]. Exploratory analyses suggest that
      crossover may have contributed to an underestimation of the true survival
      difference between the treatment groups. Ruxolitinib continued to be generally
      well tolerated; there was no pattern of worsening grade >= 3 anemia or
      thrombocytopenia with longer-term ruxolitinib exposure. These longer-term data
      continue to support the efficacy and safety of ruxolitinib in patients with
      myelofibrosis. The study is registered at clinicaltrials.gov: NCT00952289.

PMID- 25616580
TI  - The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic
      transformation of human mammary epithelial cells.
AB  - The mammalian ortholog of Drosophila ecdysoneless (Ecd) gene product regulates Rb
      E2F interaction and is required for cell cycle progression. Ecd is overexpressed
      in breast cancer and its overexpression predicts shorter survival in patients
      with ErbB2-positive tumors. Here, we demonstrate Ecd knock down (KD) in human
      mammary epithelial cells (hMECs) induces growth arrest, similar to the impact of
      Ecd Knock out (KO) in mouse embryonic fibroblasts. Furthermore, whole-genome mRNA
      expression analysis of control vs. Ecd KD in hMECs demonstrated that several of
      the top 40 genes that were down-regulated were E2F target genes. To address the
      role of Ecd in mammary oncogenesis, we overexpressed Ecd and/or mutant H-Ras in
      hTERT-immortalized hMECs. Cell cycle analyses revealed hMECs overexpressing
      Ecd+Ras showed incomplete arrest in G1 phase upon growth factor deprivation, and
      more rapid cell cycle progression in growth factor-containing medium. Analyses of
      cell migration, invasion, acinar structures in 3-D Matrigel and anchorage
      independent growth demonstrated that Ecd+Ras-overexpressing cells exhibit
      substantially more dramatic transformed phenotype as compared to cells expressing
      vector, Ras or Ecd. Under conditions of nutrient deprivation, Ecd+Ras
      overexpressing hMECs exhibited better survival, with substantial upregulation of
      the autophagy marker LC3 both at the mRNA and protein levels. Significantly,
      while hMECs expressing Ecd or mutant Ras alone did not form tumors in NOD/SCID
      mice, Ecd+Ras-overexpressing hMECs formed tumors, clearly demonstrating oncogenic
      cooperation between Ecd and mutant Ras. Collectively, we demonstrate an important
      co-oncogenic role of Ecd in the progression of mammary oncogenesis through
      promoting cell survival. 

PMID- 25616581
TI  - Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides,
      [(11)C]CB184 and [ (11)C]CB190, as a PET tracer for 18 kDa translocator protein:
      direct comparison with [ (11)C](R)-PK11195.
AB  - OBJECTIVE: We report synthesis of two carbon-11 labeled imidazopyridines TSPO
      ligands, [(11)C]CB184 and [(11)C]CB190, for PET imaging of inflammatory process
      along with neurodegeneration, ischemia or brain tumor. Biodistribution of these
      compounds was compared with that of [(11)C]CB148 and [(11)C](R)-PK11195. METHODS:
      Both [(11)C]CB184 and [(11)C]CB190 having (11)C-methoxyl group on an aromatic
      ring were readily prepared using [(11)C]methyl triflate. Biodistribution and
      metabolism of the compounds were examined with normal mice. An animal PET study
      using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued
      for proper estimation of feasibility of the radioligands to determine
      neuroinflammation process. RESULTS: [(11)C]CB184 and [(11)C]CB190 were obtained
      via O-methylation of corresponding desmethyl precursor using [(11)C]methyl
      triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as
      a TSPO radioligand was carried out using normal mice and lesioned rats. In mice,
      [(11)C]CB184 showed more uptake and specific binding than [(11)C]CB190.
      Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained
      unchanged 30 min after intravenous injection of [(11)C]CB184 and [(11)C]CB190,
      respectively. In the PET study using rats, lesioned side of the brain showed
      significantly higher uptake than contralateral side after i.v. injection of
      either [(11)C]CB184 or [(11)C](R)-PK11195. Indirect Logan plot analysis revealed
      distribution volume ratio (DVR) between the two sides which might indicate lesion
      related elevation of TSPO binding. The DVR was 1.15 +/- 0.10 for [(11)C](R)
      PK11195 and was 1.15 +/- 0.09 for [(11)C]CB184. CONCLUSION: The sensitivity to
      detect neuroinflammation activity was similar for [(11)C]CB184 and [(11)C](R)
      PK11195.

PMID- 25616584
TI  - Reliability of ultrasound evaluation of hyoid-larynx approximation with
      positional change.
AB  - We evaluated the reliability of ultrasound evaluation of hyoid-larynx
      approximation with positional change. Twenty healthy volunteers (10 men, 10
      women) participated in this study. The distance between the hyoid bone and
      thyroid cartilage was measured by ultrasound in both the sitting and supine
      positions. Hyoid-larynx approximation was defined as the shortest distance
      between the lower tip of the hyoid bone and the upper end of the thyroid
      cartilage during swallowing. The transducer was placed in a longitudinal position
      above the midline of the larynx, which allowed visualization of the hyoid bone
      and thyroid cartilage. Patients were given 5 mL of water and swallowed. The
      measurement was repeated three times to enable averaging in each position. Using
      the mean distance at rest and the shortest distance during swallowing, we
      calculated relative laryngeal elevation. There was no significant difference in
      resting distance between the hyoid bone and thyroid cartilage with positional
      change or gender, with identical relative laryngeal elevation. However, there was
      a negative correlation between the resting and approximation distance and body
      mass index. In conclusion, ultrasound evaluation in healthy volunteers revealed
      no difference in hyoid-laryngeal approximation on swallowing in either the supine
      or sitting position. This finding is likely to be of value in the investigation
      of dysphagia.

PMID- 25616583
TI  - Discriminative stimulus properties of mitragynine (kratom) in rats.
AB  - RATIONALE: Mitragynine (MG) is the primary active alkaloid extracted from the
      leaves of Mitragyna speciosa or kratom and exhibits pharmacological activities
      mediated by opioid receptors. The plant has been traditionally used for its opium
      and psychostimulant-like effects to increase work efficiency or as a substitute
      in the self-treatment of opiate addiction. OBJECTIVES: The present study was
      performed to investigate the discriminative stimulus effects of MG in rats. The
      pharmacological mechanism of MG action and its derivative, 7-hydroxymitragynine
      (7-HMG) with a specific focus on opioid receptor involvement was examined in rats
      trained to discriminate morphine from vehicle. In order to study the dual actions
      of MG, the effect of cocaine substitution to the MG discriminative stimulus was
      also performed in MG-trained rats. METHODS: Male Sprague Dawley rats were trained
      to discriminate MG from vehicle in a two-lever drug discrimination procedure
      under a tandem variable-interval (VI 60') fixed-ratio (FR 10) schedule of food
      reinforcement. RESULTS: Rats acquired the MG discrimination (15.0 mg/kg, i.p.)
      which was similar to the acquisition of morphine discrimination (5.0 mg/kg, i.p.)
      in another group of rats. MG substituted fully to the morphine discriminative
      stimulus in a dose-dependent manner, suggesting pharmacological similarities
      between the two drugs. The administration of 7-HMG derivative in 3.0 mg/kg (i.p.)
      dose engendered full generalisation to the morphine discriminative stimulus. In
      addition, the MG stimulus also partially generalised to cocaine (10.0 mg/kg,
      i.p.) stimulus. CONCLUSION: The present study demonstrates that the
      discriminative stimulus effect of MG possesses both opioid- and psychostimulant
      like subjective effects.

PMID- 25616585
TI  - Methods for using 3-D ultrasound speckle tracking in biaxial mechanical testing
      of biological tissue samples.
AB  - Being multilayered and anisotropic, biological tissues such as cardiac and
      arterial walls are structurally complex, making the full assessment and
      understanding of their mechanical behavior challenging. Current standard
      mechanical testing uses surface markers to track tissue deformations and does not
      provide deformation data below the surface. In the study described here, we found
      that combining mechanical testing with 3-D ultrasound speckle tracking could
      overcome this limitation. Rat myocardium was tested with a biaxial tester and was
      concurrently scanned with high-frequency ultrasound in three dimensions. The
      strain energy function was computed from stresses and strains using an iterative
      non-linear curve-fitting algorithm. Because the strain energy function consists
      of terms for the base matrix and for embedded fibers, spatially varying fiber
      orientation was also computed by curve fitting. Using finite-element simulations,
      we first validated the accuracy of the non-linear curve-fitting algorithm. Next,
      we compared experimentally measured rat myocardium strain energy function values
      with those in the literature and found a matching order of magnitude. Finally, we
      retained samples after the experiments for fiber orientation quantification using
      histology and found that the results satisfactorily matched those computed in the
      experiments. We conclude that 3-D ultrasound speckle tracking can be a useful
      addition to traditional mechanical testing of biological tissues and may provide
      the benefit of enabling fiber orientation computation. 

PMID- 25616586
TI  - Ethics of ambulance diversion.
AB  - Ambulance diversion is a common and controversial method used by emergency
      departments (EDs) to reduce stress on individual departments and providers and
      relieve mismatches in the supply and demand for ED beds. Under this strategy,
      ambulances bound for one hospital are redirected to another, usually under
      policies established by regional emergency medical services systems. Other
      responses to this mismatch include maladaptive behaviors (such as "boarding" in
      "hallway beds") and the development of terminology intended to normalize these
      practices, all of which are reviewed in this article. We examine the history and
      causes of diversion as well as the ethical foundations and practical consequences
      of it. We contend that (1) from a moral viewpoint, the most important stakeholder
      is the individual patient because diversion decisions are usually relative rather
      than absolute; (2) decisions regarding ambulance diversion should be made with
      careful consideration of individual patient preferences, local and state
      emergency medical services laws, and institutional surge capacity; and (3)
      authorities should consider the potential positive effects of a regional or
      statewide ban on diversion. 

PMID- 25616587
TI  - The role of inferior vena cava diameter in volume status monitoring; the best
      sonographic measurement method?
AB  - OBJECTIVES: This study aims to determine the site of and the best sonographic
      method for measurement of inferior vena cava (IVC) diameter in volume status
      monitoring. METHODS: This observational before-and-after study was performed at
      the intensive care unit of the emergency department. It included hypotensive
      adult patients with suspected sepsis who were recommended to receive at least 20
      mg/kg fluid replacement by the emergency physician. The patients were fluid
      replaced at a rate of 1000 mL/h, and maximum and minimum IVC diameters were
      measured and the Caval index calculated sonographically via both B-mode and M
      mode. Hence, IVC's volume response was assessed by a total of 6 parameters, 3
      each in M-mode and B-mode. Freidman test was used to assess the change in IVC
      diameter with fluid replacement. Wilcoxon test with Bonferroni correction was
      used to determine which measurement method more sensitively measured IVC diameter
      change. RESULTS: Twenty-eight patients with a mean age of 71.3 were included in
      the final analysis.The IVC diameter change was significant with all 6 methods (P
      < .001). The IVC minimum diameter change measured on M-mode during inspiration (M
      mode i) was the only measurement method that significantly showed diameter change
      with each 500-mL fluid replacements. The initial and the subsequent M-mode i
      values after each 500 mL of fluid were 5.65 +/- 3.34; 8.05 +/- 3.66; 10.16 +/-
      3.61, and 11.21 +/- 2.94, respectively (P < .001, P < .002, and P < .003,
      respectively). CONCLUSION: Inferior vena cava diameter was changed by fluid
      administration. The M-mode i method that most sensitively measures that change
      may be the most successful method in volume status monitoring.

PMID- 25616588
TI  - Transient false-positive urine human chorionic gonadotropin in septic shock.
AB  - Point-of-care testing for urine human chorionic gonadotropin (hCG) allows rapid
      diagnosis of pregnancy and pregnancy-related disorders at the bedside. Urine hCG
      test kits use enzyme-linked immunosorbent assay technology and incorporate 2
      types of monoclonal antibody in a sandwich structure. There have been case
      reports in a variety of disease states reporting interference with this method
      leading to false-positive results. We describe the case of a nonpregnant female
      presenting to the emergency department with septic shock secondary to severe
      colitis. Three sequential urine tests using the Clearview hCG test kit (Alere
      Limited, Stockport, United Kingdom) yielded positive results, whereas
      quantitative serum analysis was negative for hCG. This initial test result
      reverted to a true-negative result after 48 hours, suggesting the transient
      passage of an interferent into the urine at the time of initial testing. This may
      have been a molecule produced as part of the host inflammatory response or from
      bacterial synthesis of an interferent with hCG-like antigenic structure. It is
      important that clinicians are aware of the mechanisms and limitations of urine
      hCG testing and maintain a low threshold to undertake early serum hCG testing to
      confirm diagnosis.

PMID- 25616589
TI  - Abdominal migraine in the differential diagnosis of acute abdominal pain.
AB  - Although traditionally regarded as a specific pediatric disease, abdominal
      migraine may also be observed in adults. Unfortunately, however, this condition
      is frequently overlooked in the differential diagnosis of abdominal pain in the
      emergency department (ED). A 30-year-old woman presented to our ED complaining of
      abdominal pain and vomiting, lasting for 12 hours. The pain was periumbilical,
      continuous, and not associated with fever or diarrhea. The physical examination
      and the results of conventional blood tests were normal. The patient was treated
      with intravenous ketoprofen, metoclopramide, and ranitidine, obtaining a prompt
      relief of symptoms. She had a history of similar episodes in the last 15 years,
      with several ED visits, blood test examinations, ultrasonography of the abdomen,
      and upper gastrointestinal endoscopies. Celiac disease, porphyry, sickle cell
      disease, and inflammatory bowel disease were all excluded. In July 2012, she
      became pregnant, and she delivered a healthy baby on April 2013. Until November
      2014, she has remained asymptomatic. Based on the clinical characteristics of the
      abdominal pain episodes, the exclusion of any alternative diagnosis, and the
      relief of symptoms during and after pregnancy, a final diagnosis of abdominal
      migraine could be established. A skilled emergency physician should always
      consider abdominal migraine in the differential diagnosis of patients admitted to
      the ED with abdominal pain, especially when the attacks are recurrent and no
      alternative diagnosis can be clearly established.

PMID- 25616590
TI  - Evaluation of right ventricular function in Takotsubo cardiomyopathy.

PMID- 25616592
TI  - What determines frequent attendance at out-of-hours primary care services?
AB  - BACKGROUND: A detailed description of the characteristics of frequent attenders
      (FAs) at primary care services is needed to devise measures to contain the
      phenomenon. The aim of this population-registry-based research was to sketch an
      overall picture of the determinants of frequent attendance at out-of-hours (OOH)
      services, considering patients' clinical conditions and socio-demographic
      features, and whether the way patients' genaral practitioners (GPs) were
      organized influenced their likelihood of being FAs. METHODS: This study was a
      retrospective cohort study on electronic population-based records. The dataset
      included all OOH primary care service contacts from 1 January to 31 December
      2011, linked with the mortality registry and with patients' exemption from health
      care charges. A FA was defined as a patient who contacted the service three or
      more times in 12 months. A logistic regression model was constructed to identify
      independent variables associated with this outcome. RESULTS: Multivariate
      analysis showed that not only frailty and clinical variables such as psychiatric
      disease are associated with FA status, but also socio-demographic variables such
      as sex, age and income level. Alongside other environmental factors, the GP's
      gender and mode of collaboration in the provision of health services were also
      associated with OOH FA. CONCLUSION: Our study demonstrates that the determinants
      of OOH FA include not only patients' clinical conditions, but also several socio
      economic characteristics (including income level) and their GPs' organizational
      format.

PMID- 25616591
TI  - Vascularization in bone tissue engineering constructs.
AB  - Vascularization of large bone grafts is one of the main challenges of bone tissue
      engineering (BTE), and has held back the clinical translation of engineered bone
      constructs for two decades so far. The ultimate goal of vascularized BTE
      constructs is to provide a bone environment rich in functional vascular networks
      to achieve efficient osseointegration and accelerate restoration of function
      after implantation. To attain both structural and vascular integration of the
      grafts, a large number of biomaterials, cells, and biological cues have been
      evaluated. This review will present biological considerations for bone function
      restoration, contemporary approaches for clinical salvage of large bone defects
      and their limitations, state-of-the-art research on the development of
      vascularized bone constructs, and perspectives on evaluating and implementing
      novel BTE grafts in clinical practice. Success will depend on achieving full
      graft integration at multiple hierarchical levels, both between the individual
      graft components as well as between the implanted constructs and their
      surrounding host tissues. The paradigm of vascularized tissue constructs could
      not only revolutionize the progress of BTE, but could also be readily applied to
      other fields in regenerative medicine for the development of new innovative
      vascularized tissue designs.

PMID- 25616593
TI  - Gender differences in hazardous drinking among middle-aged in Europe: the role of
      social context and women's empowerment.
AB  - BACKGROUND: The aim of this study was to estimate the magnitude of gender
      differences in hazardous drinking among middle-aged people and to analyse whether
      these differences are associated with contextual factors, such as public policies
      or socioeconomic factors. METHODS: Cross-sectional design. The study population
      included 50- to 64-year-old residents of 16 European countries who participated
      in the Survey of Health, Ageing and Retirement in Europe project conducted in
      2010-12 (n = 26 017). We estimated gender differences in hazardous drinking in
      each country. To determine whether different social context or women's
      empowerment variables were associated with gender differences in hazardous
      drinking, we fitted multilevel Poisson regression models adjusted for various
      individual and country-level variables, which yielded prevalence ratios and their
      95% confidence intervals (95% CI). RESULTS: Prevalence of hazardous drinking was
      significantly higher in men than women [30.2% (95% CI: 29.1-31.4%) and 18.6% (95%
      CI: 17.7-19.4%), respectively] in most countries, although the extent of these
      differences varied between countries. Among individuals aged 50-64 years in
      Europe, risk of becoming a hazardous drinker was 1.69 times higher (95% CI: 1.45
      1.97) in men, after controlling for individual and country-level variables. We
      also found that lower values of the gender empowerment measure and higher
      unemployment rates were associated with higher gender differences in hazardous
      drinking. CONCLUSION: Countries with the greatest gender differences in hazardous
      drinking were those with the most restrictions on women's behaviour, and the
      greatest gender inequalities in daily life. Lower gender differences in hazardous
      drinking seem to be related to higher consumption among women.

PMID- 25616594
TI  - Well-being measurement and the WHO health policy Health 2010: systematic review
      of measurement scales.
AB  - BACKGROUND: Subjective well-being (SWB) contributes to health and mental health.
      It is a major objective of the new World Health Organization health policy
      framework, 'Health 2020'. Various approaches to defining and measuring well-being
      exist. We aimed to identify, map and analyse the contents of self-reported well
      being measurement scales for use with individuals more than 15 years of age to
      help researchers and politicians choose appropriate measurement tools. METHODS:
      We conducted a systematic literature search in PubMed for studies published
      between 2007 and 2012, with additional hand-searching, to identify empirical
      studies that investigated well-being using a measurement scale. For each eligible
      study, we identified the measurement tool and reviewed its components, number of
      items, administration time, validity, reliability, responsiveness and
      sensitivity. RESULTS: The literature review identified 60 unique measurement
      scales. Measurement scales were either multidimensional (n = 33) or
      unidimensional (n = 14) and assessed multiple domains. The most frequently
      encountered domains were affects (39 scales), social relations (17 scales), life
      satisfaction (13 scales), physical health (13 scales), meaning/achievement (9
      scales) and spirituality (6 scales). The scales included between 1 and 100 items;
      the administration time varied from 1 to 15 min. CONCLUSIONS: Well-being is a
      higher order construct. Measures seldom reported testing for gender or cultural
      sensitivity. The content and format of scales varied considerably. Effective
      monitoring and comparison of SWB over time and across geographic regions will
      require further work to refine definitions of SWB. We recommend concurrent
      evaluation of at least three self-reported SWB measurement scales, including
      evaluation for gender or cultural sensitivity.

PMID- 25616595
TI  - A method to distinguish between lysine acetylation and lysine ubiquitination with
      feature selection and analysis.
AB  - Lysine acetylation and ubiquitination are two primary post-translational
      modifications (PTMs) in most eukaryotic proteins. Lysine residues are targets for
      both types of PTMs, resulting in different cellular roles. With the increasing
      availability of protein sequences and PTM data, it is challenging to distinguish
      the two types of PTMs on lysine residues. Experimental approaches are often
      laborious and time consuming. There is an urgent need for computational tools to
      distinguish between lysine acetylation and ubiquitination. In this study, we
      developed a novel method, called DAUFSA (distinguish between lysine acetylation
      and lysine ubiquitination with feature selection and analysis), to discriminate
      ubiquitinated and acetylated lysine residues. The method incorporated several
      types of features: PSSM (position-specific scoring matrix) conservation scores,
      amino acid factors, secondary structures, solvent accessibilities, and disorder
      scores. By using the mRMR (maximum relevance minimum redundancy) method and the
      IFS (incremental feature selection) method, an optimal feature set containing 290
      features was selected from all incorporated features. A dagging-based classifier
      constructed by the optimal features achieved a classification accuracy of 69.53%,
      with an MCC of .3853. An optimal feature set analysis showed that the PSSM
      conservation score features and the amino acid factor features were the most
      important attributes, suggesting differences between acetylation and
      ubiquitination. Our study results also supported previous findings that different
      motifs were employed by acetylation and ubiquitination. The feature differences
      between the two modifications revealed in this study are worthy of experimental
      validation and further investigation. 

PMID- 25616596
TI  - gammaH2AX assay as DNA damage biomarker for human population studies: defining
      experimental conditions.
AB  - H2AX histone phosphorylation represents an early event in the cellular response
      against DNA double-strand breaks (DSBs), and plays a central role in sensing and
      repairing DNA damage. Therefore, the analysis of H2AX phosphorylated (gammaH2AX)
      may be possibly used as biomarker of genotoxicity and genomic instability with a
      number of applications in human epidemiology. However, the lack of an
      experimental standard leads to a wide heterogeneity in the results obtained and
      their interpretation, affecting the reliability of the assay. To address the most
      critical issues limiting the use of the gammaH2AX assay in human population
      studies, a flow cytometry analysis was performed to establish differences in
      gammaH2AX levels between fresh or cryopreserved peripheral blood lymphocytes, and
      to assess the influence of phytohemagglutinin (PHA) stimulation. To this purpose,
      cells were treated with 4 known genotoxic chemicals with different mechanisms of
      DSB induction, ie, bleomycin, methyl methanesulfonate, camptothecin, and
      actinomycin. According to our results, both unstimulated and stimulated fresh
      lymphocytes can be efficiently employed to evaluate gammaH2AX levels, but the
      sensitivity of the assay is depending upon the kind of damage observed. On the
      other hand, cryopreserved lymphocytes require PHA stimulation since unstimulated
      cells showed too high basal damage. Consequently, the protocol conditions will
      depend on the expected mechanism of production of DSB and the characteristics of
      the study design (sample collection and storage conditions, type of
      epidemiological study). Further studies are required to standardize the protocol
      of gammaH2AX assay to be employed as biomarker of genotoxicity or genomic
      instability in human population studies. 

PMID- 25616597
TI  - Suppression of the pregnane X receptor during endoplasmic reticulum stress is
      achieved by down-regulating hepatocyte nuclear factor-4alpha and up-regulating
      liver-enriched inhibitory protein.
AB  - Endoplasmic reticulum (ER) stress is recognized as a common theme in the
      development of metabolic syndrome and other diseases. Chronic liver diseases
      develop ER stress and also show decreased capacity of drug metabolism. The
      pregnane X receptor (PXR) is a master regulator of genes involved in drug
      elimination. This study was performed to determine whether ER stress condition
      decreases the expression of PXR and whether the decrease alters the induction of
      cytochrome P450 3A4 (CYP3A4). Human primary hepatocytes and HepG2 cell line
      (human hepatocellular carcinoma) were treated with brefeldin A and thapsigargin,
      2 well-established ER stressors. Without exceptions, both stressors significantly
      decreased the expression of PXR. The decrease led to reduced induction of CYP3A4.
      Reporter dissection study, electrophoretic mobility shift assay, and chromatin
      immunoprecipitation located in the PXR promoter region 2 adjacent elements
      recognized by hepatocyte nuclear factor-4alpha (HNF-4alpha) and cytidine-cytidine
      adenosine-adenosine-thymidine enhanced binding proteins (C/EBPs), respectively.
      Additional studies demonstrated that HNF-4alpha was down-regulated during ER
      stress but the expression of C/EBPbeta varied depending on a particular form of
      C/EBPbeta. Liver-enriched activator protein (LAP) was down-regulated but liver
      enriched inhibitory protein (LIP) was highly induced. Nevertheless, over
      expression of HNF-4alpha or LAP restored the expression of PXR. Interestingly,
      the very same sequence also responded to interleukin-6 (IL-6), and primary
      hepatocytes treated with thapsigargin significantly increased the level of IL-6
      mRNA. These findings establish a functional interconnection between ER stress and
      signaling of proinflammatory cytokines in the regulation of PXR expression. 

PMID- 25616598
TI  - Testing for baseline differences in randomized controlled trials: an unhealthy
      research behavior that is hard to eradicate.
AB  - BACKGROUND: According to the CONSORT statement, significance testing of baseline
      differences in randomized controlled trials should not be performed. In fact,
      this practice has been discouraged by numerous authors throughout the last forty
      years. During that time span, reporting of baseline differences has substantially
      decreased in the leading general medical journals. Our own experience in the
      field of nutrition behavior research however, is that co-authors, reviewers and
      even editors are still very persistent in their demand for these tests. The aim
      of this paper is therefore to negate this demand by providing clear evidence as
      to why testing for baseline differences between intervention groups statistically
      is superfluous and why such results should not be published. DISCUSSION: Testing
      for baseline differences is often propagated because of the belief that it shows
      whether randomization was successful and it identifies real or important
      differences between treatment arms that should be accounted for in the
      statistical analyses. Especially the latter argument is flawed, because it
      ignores the fact that the prognostic strength of a variable is also important
      when the interest is in adjustment for confounding. In addition, including
      prognostic variables as covariates can increase the precision of the effect
      estimate. This means that choosing covariates based on significance tests for
      baseline differences might lead to omissions of important covariates and, less
      importantly, to inclusion of irrelevant covariates in the analysis. We used data
      from four supermarket trials on the effects of pricing strategies on fruit and
      vegetables purchases, to show that results from fully adjusted analyses sometimes
      do appreciably differ from results from analyses adjusted for significant
      baseline differences only. We propose to adjust for known or anticipated
      important prognostic variables. These could or should be pre-specified in trial
      protocols. Subsequently, authors should report results from the fully adjusted as
      well as crude analyses, especially for dichotomous and time to event data. Based
      on our arguments, which were illustrated by our findings, we propose that
      journals in and outside the field of nutrition behavior actively adopt the
      CONSORT 2010 statement on this topic by not publishing significance tests for
      baseline differences anymore.

PMID- 25616599
TI  - HIV-1 vaccine immunogen design strategies.
AB  - An effective human immunodeficiency virus type 1 (HIV-1) vaccine is expected to
      have the greatest impact on HIV-1 spread and remains a global scientific
      priority. Only one candidate vaccine has significantly reduced HIV-1 acquisition,
      yet at a limited efficacy of 31%, and none have delayed disease progression in
      vaccinated individuals. Thus, the challenge remains to develop HIV-1 immunogens
      that will elicit protective immunity. A combination of two independent approaches
      - namely the elicitation of broadly neutralising antibodies (bNAb) to prevent or
      reduce acquisition of infection and stimulation of effective cytotoxic T
      lymphocyte (CTL) responses to slow disease progression in breakthrough infections
      (recent evidence suggests that CTLs could also block HIV-1 from establishing
      persistent infection) - is the current ideal. The purpose of this review is to
      summarise strategies and progress in the design and testing of HIV-1 immunogens
      to elicit bNAb and protective CTL immune responses. Recent advances in mimicking
      the functional native envelope trimer structure and in designing structurally
      stabilised bNAb epitope forms to drive development of germline precursors to
      mature bNAb are highlighted. Systematic or computational approaches to T cell
      immunogen design aimed at covering viral diversity, increasing the breadth of
      immune responses and/or reducing viable viral escape are discussed. We also
      discuss a recent novel vaccine vector approach shown to induce extremely broad
      and persistent T cell responses that could clear highly pathogenic simian
      immunodeficiency virus (SIV) early after infection in the monkey model. While in
      vitro and animal model data are promising, Phase II and III human clinical trials
      are ultimately needed to determine the efficacy of immunogen design approaches. 

PMID- 25616600
TI  - Effect of the novel functional fibre, polyglycoplex (PGX), on body weight and
      metabolic parameters: A systematic review of randomized clinical trials.
AB  - BACKGROUND & AIMS: Hundreds of dietary supplements are marketed as weight loss
      pills, but the evidence for effectiveness for most is unproven. The objective of
      this review was to critically appraise and evaluate the evidence from published
      randomized clinical trials (RCTs) examining the effectiveness of polyglycoplex
      (PGX), a novel functional fibre, on body weight and metabolic parameters.
      METHODS: We conducted electronic searches in Medline, Embase, Amed, Cinahl and
      The Cochrane Library. Only double-blinded RCTs were considered for inclusion. The
      reporting quality of included studies was assessed using the Cochrane criteria.
      Two reviewers independently determined eligibility, assessed the quality of
      reporting, and extracted the data. RESULTS: We included four RCTs with a total of
      217 participants. The RCTs varied in the quality of their reporting. The evidence
      from the RCTs suggested that PGX has no significant effects on body weight;
      however, significant reductions were noted for total and LDL cholesterol. Adverse
      events reported included diarrhea and abdominal bloating. CONCLUSION: The
      evidence from available RCTs does not indicate that PGX intake causes reductions
      in body weight. PGX may cause reductions in total and LDL cholesterol. Few trials
      examining the effects of PGX have been conducted; they are characterized by small
      sample sizes, deficiencies in reporting quality, and are funded by a single
      manufacturer. Future clinical trials evaluating its effect should be adequately
      powered and better reported.

PMID- 25616601
TI  - Nutrition therapy in critically ill patients- a review of current evidence for
      clinicians.
AB  - The provision of nutrition to critically ill patients is internationally accepted
      as standard of care in intensive care units (ICU). Nutrition has the potential to
      positively impact patient outcomes, is relatively inexpensive compared to other
      commonly used treatments, and is increasingly identified as a marker of quality
      ICU care. Furthermore, we are beginning to understand its true potential, with
      positive and deleterious consequences when it is delivered inappropriately. As
      with many areas of medicine the evidence is rapidly changing and often
      conflicting, making interpretation and application difficult for the individual
      clinician. This narrative review aims to provide an overview of the major
      evidence base on nutrition therapy in critically ill patients and provide
      practical suggestions. 

PMID- 25616602
TI  - Latitudinal concordance between biogeographic regionalization, community
      structure, and richness patterns: a study on the reptiles of China.
AB  - Latitudinal patterns in species richness may be affected by both continuous
      variations in macroecological factors as well as discrete change between
      biogeographic regions. We examined whether latitudinal reptilian richness and
      community structure in China were best explained by three macroecological
      patterns (mid-domain effects, Rapoport's rule effects, or environmental
      correlates) within or across the ranges of biogeographic realms. The results
      showed that (1) there was a weak mid-domain effect within the Oriental Realm.
      However, the mid-domain effect was detected neither at the overall regional scale
      nor in the Palaearctic Realm. (2) Rapoport's rule was only weakly supported for
      reptilian fauna in China at lower latitudinal areas. (3) Environmental variables
      were more strongly correlated with species' latitudinal community structure and
      richness patterns at the scale of biogeographic realms. Based on the faunal
      similarity of reptilian community across latitudinal bands, we proposed a
      latitudinal delineation scheme at 34 degrees  N for dividing East Asia into
      Oriental and Palaearctic biogeographic realms. At last, at the functional group
      level, we also evaluated the relevant ecological patterns for lizard and snake
      species across different latitudinal bins, showing that the distributions of
      lizards presented strong mid-domain effects at the latitudinal ranges within the
      Oriental Realm and over the whole range but did not support Rapoport's rule. In
      comparison, snake species supported Rapoport's rule at low latitudinal zones but
      did not present any remarkable mid-domain effects at any spatial extents. In
      conclusion, biogeographic realms are an appropriate scale for studying
      macroecological patterns. Reptilian latitudinal richness patterns of China were
      explained by a combination of environmental factors and geometric constraints,
      while the latitudinal community structure patterns were greatly affected by
      environmental gradients. Functional guilds present differentiated macroecological
      patterns along the latitudinal gradients. 

PMID- 25616603
TI  - Modulation of fasciculation frequency in amyotrophic lateral sclerosis.

PMID- 25616604
TI  - The prognostic value of CSF neurofilaments in multiple sclerosis at 15-year
      follow-up.

PMID- 25616605
TI  - BCIs and physical medicine and rehabilitation: the future is now.

PMID- 25616606
TI  - BCI in patients with disorders of consciousness: clinical perspectives.
AB  - The reestablishment of communication is one of the main goals for patients with
      disorders of consciousness (DOC). It is now established that many DOC patients
      retain the ability to process stimuli of varying complexity even in the absence
      of behavioural response. Motor impairment, fatigue, attention disorders might
      contribute to the difficulty of communication in this population. Brain-computer
      interfaces (BCI) might be helpful in restoring some communication ability in
      these patients. After a definition of the different disorders of consciousness
      that might benefit from BCI, brain markers able to detect cognitive processes and
      awareness in the absence of behavioural manifestation are described. Can these
      markers be willfully modulated and used to restore communication in DOC patients?
      In order to answer this question, three paradigmatic articles using either
      functional imaging or electrophysiology are critically analysed with regard to
      clinical applications. It appears that the use of fMRI is limited from a clinical
      point of view, whereas the EEG seems more feasible with possible BCI applications
      at the patient's bedside. However, at this stage, several limitations are pointed
      out: the lack of awareness in itself, the lack of sensitivity of the technique,
      atypical pattern of brain activity in brain damaged patients. The challenge is
      now to select the best candidates, to improve the efficiency, portability and
      cost of these techniques. Although this innovative technology may concern a
      minority of DOC patients, it might offer the possibility to restore or improve
      communication to heavily disabled patients and meanwhile detect a signature of
      awareness. 

PMID- 25616607
TI  - Efficacy of standard therapies against Ureaplasma species and persistence among
      men with non-gonococcal urethritis enrolled in a randomised controlled trial.
AB  - OBJECTIVE: Ureaplasma urealyticum biovar 2 (UU-2), but not Ureaplasma parvum
      (UP), has been associated with non-gonococcal urethritis (NGU), but little is
      known about species-specific responses to standard therapies. We examined species
      specific treatment outcomes and followed men with treatment failure for 9 weeks.
      METHODS: From May 2007 to July 2011, men aged >=16 attending a sexually
      transmitted disease (STD) clinic in Seattle, Washington, with NGU (urethral
      discharge or urethral symptoms plus >=5 polymorphonuclear leucocytes /high
      powered field) enrolled in a double-blind, randomised trial. Participants
      received active azithromycin (1 g) + placebo doxycycline or active doxycycline
      (100 mg twice a day *7 days) + placebo azithromycin. Ureaplasma were detected in
      culture followed by species-specific PCR. Outcomes were assessed at 3, 6 and 9
      weeks. At 3 weeks, men with persistent Ureaplasma detection received 'reverse
      therapy' (e.g., active doxycycline if they first received active azithromycin).
      At 6 weeks, persistently positive men received moxifloxacin (400 mg*7 days).
      RESULTS: Of 490 men, 107 (22%) and 60 (12%) were infected with UU-2 and UP,
      respectively, and returned at 3 weeks. Persistent detection was similar for UU-2
      infected men initially treated with azithromycin or doxycycline (25% vs. 31%;
      p=0.53), but differed somewhat for men with UP (45% vs. 24%; p=0.11). At 6 weeks,
      57% of UU-2-infected and 63% of UP-infected men who received both drugs had
      persistent detection. Failure after moxifloxacin occurred in 30% and 36%,
      respectively. Persistent detection of UU-2 or UP was not associated with
      signs/symptoms of NGU. CONCLUSIONS: Persistent detection after treatment with
      doxycycline, azithromycin and moxifloxacin was common for UU and UP, but not
      associated with persistent urethritis. TRIAL REGISTRATION NUMBER: NCT00358462.

PMID- 25616608
TI  - Association between neurovascular contact and clinical characteristics in
      classical trigeminal neuralgia: A prospective clinical study using 3.0 Tesla MRI.
AB  - BACKGROUND: Previous studies demonstrated that a severe neurovascular contact
      (NVC) causing displacement or atrophy of the trigeminal nerve is highly
      associated with classical trigeminal neuralgia (TN). There are no studies
      describing the association between the clinical characteristics of TN and severe
      NVC. METHODS: Clinical characteristics were prospectively collected from
      consecutive TN patients using semi-structured interviews in a cross-sectional
      study design. We evaluated 3.0 Tesla MRI blinded to the symptomatic side.
      RESULTS: We included 135 TN patients. Severe NVC was more prevalent in men (75%)
      compared to women (38%) (p < 0.001), and the odds in favor of severe NVC on the
      symptomatic side were 5.1 times higher in men compared to women (95% CI 2.3-10.9,
      p < 0.001). There was no difference between patients with and without severe NVC
      in age (>=60 years vs. <60) (OR 1.6 95% CI (0.8-3.4), p = 0.199) or duration of
      disease (p = 0.101). CONCLUSIONS: Severe NVC was much more prevalent in men than
      in women, who may more often have other disease etiologies causing or
      contributing to TN. Severe NVC was not associated with age or with duration of
      disease.

PMID- 25616609
TI  - Sounding out migraine-related interactions between the brainstem and cortex.

PMID- 25616610
TI  - Resistant starch alters colonic contractility and expression of related genes in
      rats fed a Western diet.
AB  - BACKGROUND AND AIM: Dietary fiber shortens gut transit time, but data on the
      effects of fiber components (including resistant starch, RS) on intestinal
      contractility are limited. We have examined RS effects in male Sprague-Dawley
      rats fed either a high-amylose maize starch (HAMS) or a wholemeal made from high
      amylose wheat (HAW) on ileal and colonic contractility ex vivo and expression of
      genes associated with smooth muscle contractility. METHODS: Rats were fed diets
      containing 19 % fat, 20 % protein, and either low-amylose maize starch (LAMS),
      HAMS, wholemeal low-amylose wheat (LAW) or HAW for 11 week. Isolated ileal and
      proximal colonic sections were induced to contract electrically, or by receptor
      independent (KCl) or receptor-dependent agents. Colonic gene expression was
      assessed using an Affymetrix microarray. RESULTS: Ileal contractility was
      unaffected by treatment. Maximal proximal colonic contractility induced
      electrically or by angiotensin II or carbachol was lower for rats fed HAMS and
      LAW relative to those fed LAMS (P < 0.05). The colonic expression of genes,
      including cholinergic receptors (Chrm2, Chrm3), serotonin receptors (Htr5a,
      Htr7), a protease-activated receptor (F2r), a prokineticin receptor (Prokr1),
      prokineticin (Prok1), and nitric oxide synthase 2 (Nos2), was altered by dietary
      HAMS relative to LAMS (P < 0.05). HAW did not significantly affect these genes or
      colonic contractility relative to effects of LAMS. CONCLUSIONS: RS and other
      fiber components could influence colorectal health through modulation of stool
      transit time via effects on muscular contractility.

PMID- 25616611
TI  - Characteristics of gastrointestinal bleeding after placement of continuous-flow
      left ventricular assist device: a case series.
AB  - BACKGROUND: Medical management of patients with continuous-flow left ventricular
      assist devices (LVADs) remains challenging for the gastroenterologist given their
      high risk of gastrointestinal bleeding (GIB) and need for continuous
      anticoagulation. AIMS: Our aim was to better characterize LVAD patients who
      presented with a GIB at our facility and delineate the prevalence, presentation,
      time to diagnosis, management, and therapeutic endoscopic interventions,
      including small bowel tools that may offer additional benefit. METHODS: We
      retrospectively reviewed adult patients (>18 years) who underwent LVAD
      implantation at our tertiary care facility between October 2011 and October 2013.
      Electronic medical records were reviewed for presenting symptoms, average days to
      initial and repeat GIB, hospital course, and techniques that led to diagnosis and
      hemostasis. RESULTS: Eighteen patients underwent LVAD implantation, of which 61 %
      presented with a GIB for a total of 20 presentations (1.8 per patient). Mean time
      to initial GIB was 154 days. Patients required an average of 1.8 endoscopic
      procedures per admission. Esophagogastroduodenoscopy (EGD) and push enteroscopy
      (PE) were more likely to lead to a diagnosis, and EGD was the most commonly used
      diagnostic tool at initial presentation. Sixty percent of patients who initially
      received EGD presented with a recurrent GIB and required PE, which was diagnostic
      and therapeutic for small bowel angiodysplasias in 80 % of cases. CONCLUSION: We
      found a higher GIB rate compared with prior studies. Bleeding events were
      associated with multiple procedures and interventions. We recommend an
      algorithmic approach to LVAD patients who bleed. Our experience suggests that PE
      is warranted at initial presentation in order to achieve hemostasis, prevent
      recurrent GIB, and decrease subsequent readmission rates.

PMID- 25616612
TI  - Endoplasmic reticulum stress may not be involved in intestinal epithelial cell
      apoptosis in experimental acute pancreatitis.
AB  - OBJECTIVES: To investigate whether endoplasmic reticulum (ER) stress is activated
      in the intestinal epithelium of acute pancreatitis (AP), and whether it is one of
      the inducing factors of the intestinal epithelial cell apoptosis in AP. METHODS:
      Twenty-four rats were randomly divided into two groups. AP was induced via
      retrograde injection of 3 % sodium taurocholate into the pancreatic duct. As a
      control group, rats received a sham operation. Forty-eight hours after the
      operation, the ultrastructural changes of ileal epithelial cells were
      investigated by transmission electron microscope. The protein expressions of
      GRP78, CHOP, caspase-12, and JNK in the ileal epithelium were determined by
      immunohistochemistry, and apoptosis was determined by TdT-mediated dUTP nick end
      labeling. The mRNA expressions of GRP78, CHOP, caspase-12, and JNK in the ileal
      epithelium were determined using quantitative RT-PCR. RESULTS: The ileal
      epithelium in rats with AP had significantly higher apoptotic cells compared with
      that of the control rats (P < 0.05). ER stress was activated in the ileal
      epithelium, which was characterized by dilated, irregular ER and upregulated
      expressions of GRP78 mRNA and protein. The mRNA and protein expressions of CHOP,
      caspase-12, and JNK in rats with AP were similar to that in the control rats (P >
      0.05). CONCLUSIONS: ER stress is induced in intestinal epithelium during AP;
      however, ER stress is not likely to be involved in the apoptosis of the
      intestinal epithelium during AP.

PMID- 25616613
TI  - Colonization of Solidago altissima by the specialist aphid Uroleucon
      nigrotuberculatum: effects of genetic identity and leaf chemistry.
AB  - In dominant old-field plant species, genotypic variation in traits important for
      herbivorous insects may explain variation in insect species abundance. While the
      importance of plant genetic identity on arthropod abundance has been
      demonstrated, specific factors that drive genotype choice by insects remain
      largely unknown. Sixteen genotypes of the widely distributed plant species
      Solidago altissima were used to investigate the possible role of nutrients and
      terpene secondary metabolites in shaping the abundance of a common specialist
      aphid, Uroleucon nigrotuberculatum. Ramets were propagated in a greenhouse and
      then transferred to a natural field setting. After 76 days, aphid abundance was
      quantified and leaf tissue assayed for nutrients and terpenes. Aphids/g plant
      biomass significantly differed among genotypes, with a 30-fold difference
      observed among plant genotypes. Leaf nitrogen, C:N ratio and water did not vary
      among genotypes. Of eight terpenes quantified, five were influenced by plant
      genotype. Aphid abundance increased marginally with the concentration of the
      monoterpene beta-pinene in leaf tissue (P = 0.056). A partial least squares
      analysis determined that nutritional chemicals did not explain aphid responses,
      while 49% of the variation in aphid colonization among genotypes was explained by
      terpenes. This study is one of the first to demonstrate that variation in
      allelochemicals may be related to differences in the abundance of a key herbivore
      among genotypes of a plant species that exhibits large intraspecific genetic
      variation.

PMID- 25616614
TI  - Consolidation of first remission using radioimmunotherapy with yttrium-90
      ibritumomab-tiuxetan in adult patients with Burkitt lymphoma.
AB  - The addition of anti-CD20 antibodies to high intensity polychemotherapy regimens
      has improved response and survival rates in newly diagnosed patients with Burkitt
      lymphoma (BL). However, the role of additional anti-CD20 directed
      radioimmunotherapy for consolidation of first remission (CR1) has not been
      reported so far in BL patients receiving rituximab during first-line treatment.
      We compared five BL patients receiving Y-90-IT radioimmunotherapy consolidation
      in CR1 to 22 consecutive BL patients without consolidation. We observed that Y-90
      IT treatment was associated with clinically relevant myelosuppression. After a
      median follow-up of 50 months, none of the patients with Y-90-IT treatment
      relapsed, and no patient died. In contrast, one patient (4.5%) in the non-Y-90-IT
      group relapsed (50 months-PFS 95.5%; p=0.6336), and one patient died (50 months
      OS 95.5%; p=0.6171). In conclusion, our data suggest that survival rates are
      excellent and equal in rituximab pretreated BL patients with or without Y-90-IT
      consolidation in first remission. 

PMID- 25616615
TI  - Congenital focal lymphedema as a diagnostic clue to tuberous sclerosis complex:
      report of two cases diagnosed by ultrasound.
AB  - Tuberous sclerosis complex (TSC) is a familial disorder characterized by benign
      hamartomas in the brain and other organs. Generally, the diagnosis of TSC is
      relatively easy, based on a medical history, a physical examination, and imaging
      findings. However, it can be difficult to consider a possibility of TSC in
      neonates and infants when congenital lymphedema is the sole external
      manifestation, because lymphedema associated with TSC is extremely rare. Herein,
      we report two cases of TSC showing congenital lymphedema at the initial
      presentation. Both patients were girls, and their sole complaint was congenital
      lymphedema. We diagnosed TSC using ultrasound focusing on the kidney, heart, and
      brain in addition to the extremity showing lymphedema. Awareness of a potential
      association of congenital lymphedema with TSC may assist in the diagnosis of TSC
      by ultrasound. 

PMID- 25616616
TI  - Magnetic resonance imaging findings compared with histological findings of the
      labrum in hip osteoarthritis.

PMID- 25616618
TI  - [Acute pancreatitis by Ascaris lumbricoides].

PMID- 25616617
TI  - Immunomodulatory effects of Trichinella spiralis-derived excretory-secretory
      antigens.
AB  - Helminth-derived products, either released into the circulation during the course
      of the infection or isolated after in vitro cultivation of the parasite and
      applied by the injection, are able to suppress the host immune response to
      autoantigens and allergens, but mechanisms could differ. Prophylactic application
      of Trichinella spiralis excretory-secretory muscle larvae (ES L1) products
      ameliorates experimental autoimmune encephalomyelitis (EAE) with the same success
      as infection did. However, a shift to the Th2-type response in the periphery and
      in the central nervous system, accompanied by activation of regulatory
      mechanisms, had a striking, new feature of increased proportion of unconventional
      CD4(+)CD25(-)Foxp3(+) regulatory cells both in the periphery and in the central
      nervous system of animals treated with ES L1 before the induction of EAE. 

PMID- 25616619
TI  - [Polyostotic fibrous dysplasia].

PMID- 25616620
TI  - [Reply].

PMID- 25616621
TI  - Results of nerve reconstructions in treatment of obstetrical brachial plexus
      injuries.
AB  - BACKGROUND: The aim of this study was to evaluate the results achieved using
      various surgical techniques in patients with partial and total obstetrical
      brachial plexus palsy. METHODS: From 2000 to 2013, 33 patients with obstetrical
      brachial plexus injury underwent surgery. Twenty had follow-up periods greater
      than 24 months and met the criteria for inclusion in the study. All patients were
      evaluated using the Active Movement Scale. RESULTS: The outcomes of different
      nerve reconstructive procedures including nerve transfers, nerve grafting after
      neuroma resection and end-to-side neurorrhaphy are presented. The overall success
      rate in upper plexus birth injury was 80 % in shoulder abduction, 50 % in
      external rotation and 81.8 % in elbow flexion with median follow-ups of 36
      months. Success rate in complete paralysis was 87 % in finger and thumb flexion,
      87 % in shoulder abduction and 75 % in elbow flexion; the median follow-up was 46
      months. Useful reanimation of the hand was obtained in both patients who
      underwent end-to-side neurotization. CONCLUSION: Improved function can be
      obtained in infants with obstetrical brachial plexus injury with early surgical
      reconstruction.

PMID- 25616622
TI  - Selective peripheral denervation for the treatment of spasmodic torticollis: long
      term follow-up results from 648 patients.
AB  - BACKGROUND: Selective peripheral denervation (SPD) is currently the primary
      surgical treatment for spasmodic torticollis (ST). Our objective here is to
      report on the outcome of patients treated with this procedure for ST in our
      department. METHODS: Between June 1995 and June 2013, 648 patients underwent SPD
      for ST. We included 293 women (45.2 %) and 355 men (54.8 %) with a mean age of
      41.1 years (range, 8-74 years) at the onset of dystonia. Surgery was performed at
      a mean of 3.6 years (range, 1-32 years) after onset of symptoms. Data on clinical
      presentation, radiological studies, operation tragedy, clinical outcomes and
      complications were analysed retrospectively. For evaluation of clinical outcomes,
      patients' responses were assessed using the Toronto Western Spasmodic Torticollis
      Rating Scale (TWSTRS). RESULTS: Results were obtained from all 648 patients with
      a follow-up period ranging from 11 months to 154 months (mean, 33.4 months). The
      mean preoperative TWSTRS score was 54.7 +/- 18.3 points (range, 39-67 points),
      which decreased to 31.1 +/- 11.6 points postoperatively (range, 1-67 points); a
      significant improvement was observed between preoperative and postoperative
      TWSTRS evaluation; the clinical improvement of TWSTRS was 73.5 +/- 11.9 %. In
      addition, no deaths and serious complications occurred in this cohort of
      patients. CONCLUSIONS: SPD is an effective surgical method for patients with ST.
      This procedure should be recommended if conservative therapy does not offer
      satisfactory relief of symptoms.

PMID- 25616623
TI  - Evaluation and Mitigation of Secondary Dose Delivered to Electronic Systems in
      Proton Therapy.
AB  - PURPOSE: To evaluate the scattered and secondary radiation fields present in and
      around a passive proton treatment nozzle. In addition, based on these initial
      tests and system reliability analysis, to develop, install, and evaluate a
      radiation shielding structure to protect sensitive electronics against single
      event effects (SEE) and improve system reliability. METHODS AND MATERIALS:
      Landauer Luxel+ dosimeters were used to evaluate the radiation field around one
      of the gantry-mounted passive proton delivery nozzles at Loma Linda University
      Medical Center's James M Slater, MD Proton Treatment and Research Center. These
      detectors use optically stimulated luminescence technology in conjunction with CR
      39 to measure doses from X-ray, gamma, proton, beta, fast neutron, and thermal
      neutron radiation. The dosimeters were stationed at various positions around the
      gantry pit and attached to racks on the gantry itself to evaluate the dose to
      electronics. Wax shielding was also employed on some detectors to evaluate the
      usefulness of this material as a dose moderator. To create the scattered and
      secondary radiation field in the gantry enclosure, a polystyrene phantom was
      placed at isocenter and irradiated with 250 MeV protons to a dose of 1.3 kGy over
      16 hours. Using the collected data as a baseline, a composite shielding structure
      was created and installed to shield electronics associated with the precision
      patient positioner. The effectiveness of this shielding structure was evaluated
      with Landauer Luxel+ dosimeters and the results correlated against system uptime.
      RESULTS: The measured dose equivalent ranged from 1 to 60 mSv, with
      proton/photon, thermal neutron, fast neutron, and overall dose equivalent
      evaluated. The position of the detector/electronics relative to both isocenter
      and also neutron-producing devices, such as the collimators and first and second
      scatterers, definitely had a bearing on the dose received. The addition of 1-inch
      thick wax shielding decreased the fast neutron component by almost 50%, yet this
      yielded a corresponding average increase in thermal neutron dose of 150% as there
      was no Boron-10 component to capture thermal neutrons. Using these data as a
      reference, a shielding structure was designed and installed to minimize radiation
      to electronics associated with the patient positioner. The installed shielding
      reduced the total dose experienced by these electronics by a factor of 5 while
      additionally reducing the fast and thermal neutron doses by a factor of 7 and 14,
      respectively. The reduction in radiation dose corresponded with a reduction of
      SEE-related downtime of this equipment from 16.5 hours to 2.5 hours over a 6
      month reporting period. CONCLUSIONS: The data obtained in this study provided a
      baseline for radiation exposures experienced by gantry- and pit-mounted
      electronic systems. It also demonstrated and evaluated a shielding structure
      design that can be retrofitted to existing electronic system installations. It is
      expected that this study will benefit future upgrades and facility designs by
      identifying mechanisms that may minimize radiation dose to installed electronics,
      thus improving facility uptime.

PMID- 25616624
TI  - Regarding the Credibility of Data Showing an Alleged Association of Cancer with
      Radiation from CT Scans.
AB  - Computed tomography (CT) scans are of high clinical value as a diagnostic
      technique, and new applications continue to be identified. However, their
      application is challenged by emerging concerns regarding carcinogenesis from
      their radiation. Recent articles made a significant contribution to the above
      mentioned concerns by reporting evidence for direct association of the radiation
      from CT scans with cancer. Such interpretation of the data has already been
      criticized; there is the possibility of reverse causation due to confounding
      factors. Nevertheless, such work has had a high impact, with one article being
      cited more than 300 times from the Web of Science Core Collection within 2 years.
      However, the data points on cancer relative risk versus CT dose in that article
      fit straight lines corresponding to the linear no-threshold hypothesis
      suspiciously well. Here, by applying rigorous statistical analysis, it is shown
      that the probability of the fit truly being that good or better is only 2%. The
      results of such studies therefore appear "too good to be true" and the
      credibility of their conclusions must be questioned. 

PMID- 25616625
TI  - Disease activity of pregnant women with systemic lupus erythematosus.

PMID- 25616626
TI  - Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized
      infectious patients.
AB  - BACKGROUND: hospitalized patients with serious infections treated with
      aminoglycosides are at risk of developing nephrotoxicity. Previous clinical
      studies have shown that the pharmacokinetics of aminoglycosides in humans follow
      a circadian rhythm. Therefore, the time of administration could have important
      clinical implications with respect to the risk of developing aminoglycoside
      associated nephrotoxicity in patients treated with once daily dosing regimens.
      OBJECTIVE: To examine the effect of the time period of administration on
      aminoglycoside exposure and the incidence of nephrotoxicity in a large population
      of hospitalized patients with serious infections. SETTING: General ward and
      intensive care unit of a teaching hospital. METHOD: In this retrospective cohort
      study, patients treated with intravenous tobramycin or gentamicin were eligible
      for inclusion. Patients were divided into three groups by time of administration:
      morning, afternoon and night. MAIN OUTCOME MEASURE: Pharmacokinetic parameters
      and the incidences of nephrotoxicity were compared between the morning, afternoon
      and evening groups. Results 310 general ward and 411 intensive care unit patients
      were included. No significant differences were found in patient characteristics
      between the morning, afternoon and night groups. The time period of
      administration did not affect aminoglycoside pharmacokinetics or the incidence of
      nephrotoxicity. CONCLUSION: The time of administration has no effect on the
      pharmacokinetics or nephrotoxicity of once daily dosed aminoglycosides in
      hospitalized patients. Consequently, we advise aminoglycosides to be administered
      as soon as possible in case of (suspected) severe hospital-acquired infections
      and subsequent dosages to be based on therapeutic drug monitoring to optimize the
      efficacy/toxicity balance.

PMID- 25616627
TI  - Home pharmacies in Serbia: an insight into self-medication practice.
AB  - BACKGROUND: Worldwide data indicate that self-medication is frequently used
      inappropriately. Although self-medication is encouraged in most of the countries
      by introducing over-the-counter drugs, it bears the risk of misuse of drugs
      issued on prescription due to low observance of legislation of medicines
      requiring prescription by some pharmacies. OBJECTIVE: The objective of this study
      was to explore the self-medication practice, with an emphasis on self-medication
      with prescription-only medications. SETTING: Households in Novi Sad city, Serbia.
      METHOD: The study was conducted over 8 month period (December 2011-July 2012) and
      involved a random sample of households. The questionnaire-based study and
      personal insight into household drug supplies was performed by a trained
      interviewer. Main outcome measure Number of drugs obtained without prescription
      or without consulting a physician in surveyed households. RESULTS: The total
      number of drug items present in the 383 households was 4,384 with a median of 11
      drugs per household. More than a half of drugs in households were prescription
      only medication (58.5 %). Approximately one third of prescription-only
      medications were obtained without prescription. The most common drugs obtained
      without prescription were anti-inflammatory and antirheumatic products and
      antibacterials for systemic use. Ibuprofen and diclofenac were the most common
      self-medicated drugs. Number of prescription-only medications bought with ought
      prescription was significantly higher in households with children under 12 years
      of age compared to other types of households. CONCLUSION: Our survey indicated
      that self-medication with prescription drugs appeared to be a rather common
      practice, which is far away from the concept of "responsible self-medication",
      especially regarding antibiotics.

PMID- 25616628
TI  - Immunohistochemical detection of intrathrombotic IL-6 and its application to
      thrombus age estimation.
AB  - We immunohistochemically examined intrathrombotic IL-6 expression using a murine
      model of deep vein thrombosis induced by the ligation of the inferior vena cava
      (IVC) and discussed the availability of intrathrombotic IL-6 for thrombus age
      estimation. IL-6(+) cells could be first detected at 1 day after IVC ligation in
      three of five samples, and all samples with postligation intervals of 3 days or
      more had intrathrombotic IL-6(+) cells. Thereafter, the numbers of IL-6(+) cells
      were elevated with the increase of postligation intervals. Double-color
      immunofluorescence analyses demonstrated that IL-6 was mainly expressed by
      intrathrombotic macrophages. In all samples with postligation intervals of 5 days
      or less, the IL-6/macrophage ratio (IL-6/Mphi) was <0.5. In contrast, the IL
      6/Mphi was greater than 0.5 at >=7 days after the IVC ligation. These
      observations implied that IL-6/Mphi ratios of >0.5 would strongly indicate
      thrombus ages of >=7 days. Reciprocally, the ratios of less than 0.5 would
      suggest thrombus ages of <=5 days. The present study demonstrated that the
      immunohistochemical detection of IL-6 was suitable to estimate the age of venous
      thrombi.

PMID- 25616629
TI  - The 'triple contrast' method in experimental wound ballistics and backspatter
      analysis.
AB  - In practical forensic casework, backspatter recovered from shooters' hands can be
      an indicator of self-inflicted gunshot wounds to the head. In such cases,
      backspatter retrieved from inside the barrel indicates that the weapon found at
      the death scene was involved in causing the injury to the head. However,
      systematic research on the aspects conditioning presence, amount and specific
      patterns of backspatter is lacking so far. Herein, a new concept of backspatter
      investigation is presented, comprising staining technique, weapon and target
      medium: the 'triple contrast method' was developed, tested and is introduced for
      experimental backspatter analysis. First, mixtures of various proportions of
      acrylic paint for optical detection, barium sulphate for radiocontrast imaging in
      computed tomography and fresh human blood for PCR-based DNA profiling were
      generated (triple mixture) and tested for DNA quantification and short tandem
      repeat (STR) typing success. All tested mixtures yielded sufficient DNA that
      produced full STR profiles suitable for forensic identification. Then, for
      backspatter analysis, sealed foil bags containing the triple mixture were
      attached to plastic bottles filled with 10% ballistic gelatine and covered by a 2
      3-mm layer of silicone. To simulate backspatter, close contact shots were fired
      at these models. Endoscopy of the barrel inside revealed coloured backspatter
      containing typable DNA and radiographic imaging showed a contrasted bullet path
      in the gelatine. Cross sections of the gelatine core exhibited cracks and
      fissures stained by the acrylic paint facilitating wound ballistic analysis.

PMID- 25616630
TI  - MicroRNAs: a macroview into focal segmental glomerulosclerosis.

PMID- 25616631
TI  - Recognizing our limits: deficiencies in end-of-life education for nephrology
      trainees.

PMID- 25616632
TI  - Dialysis vasculopathy-subtle thoughts of a deeply damaged brain.

PMID- 25616633
TI  - In reply to 'discontinuation of eculizumab maintenance treatment for atypical
      hemolytic uremic syndrome'.

PMID- 25616634
TI  - Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic
      syndrome.

PMID- 25616635
TI  - Once-weekly hemodialysis: a single-center experience.

PMID- 25616636
TI  - Compensation and incentives for living organ donors: a double-edged sword that
      may resolve the current organ shortage crisis.

PMID- 25616637
TI  - Quiz page February 2015: renal colic in an adolescent.

PMID- 25616638
TI  - Effect of ultrasound radiation duration on emulsification and demulsification of
      paraffin oil and surfactant solution/brine using Hele-shaw models.
AB  - Ultrasound technique is one of the unconventional enhanced oil recovery methods
      which has been of interest for more than six decades. However, the majority of
      the oil recovery mechanisms under ultrasound reported in the previous studies are
      theoretical. Emulsification is one of the mechanisms happening at the interface
      of oil and water in porous media under ultrasound. Oppositely, ultrasound is one
      of the techniques using in oil industry for demulsification of oil/water
      emulsion. Therefore, the conditions in which emulsification becomes dominant over
      demulsification under ultrasound should be more investigated. Duration of
      ultrasound radiation could be one of the factors affecting emulsification and
      demulsification processes. In this study a technique was developed to investigate
      the effect of long and short period of ultrasound radiation on emulsification and
      demulsification of paraffin oil and surfactant solution in porous media. For this
      purpose, the 2D glass Hele-shaw models were placed inside the ultrasonic bath
      under long and short period of radiation of ultrasound. A microscope was used
      above the model for microscopic studies on the interface of oil and water.
      Diffusion of phases and formation of emulsion were observed in both long and
      short period of application of ultrasound at the beginning of ultrasound
      radiation. However, by passing time, demulsification and coalescence of brine
      droplets inside emulsion was initiated in long period of ultrasound application.
      Therefore, it was concluded that emulsification could be one of the significant
      oil recovery mechanisms happening in porous media under short period of
      application of ultrasound. 

PMID- 25616639
TI  - Effective ultrasonication process for better colloidal dispersion of nanofluid.
AB  - Improving dispersion stability of nanofluids through ultrasonication has been
      shown to be effective. Determining specific conditions of ultrasonication for a
      certain nanofluid is necessary. For this purpose, nanofluids of varying
      nanoparticle concentrations were prepared and studied to find out a suitable and
      rather mono-dispersed concentration (i.e., 0.5 vol.%, determined through
      transmission electron microscopy (TEM) analyses). This study aims to report
      applicable ultrasonication conditions for the dispersion of Al2O3 nanoparticles
      within H2O through the two-step production method. The prepared samples were
      ultrasonicated via an ultrasonic horn for 1-5h at two different amplitudes (25%
      and 50%). The microstructure, particle size distribution (PSD), and zeta
      potentials were analyzed to investigate the dispersion characteristics. Better
      particle dispersion, smaller aggregate sizes, and higher zeta potentials were
      observed at 3 and 5h of ultrasonication duration for the 50% and 25% of sonicator
      power amplitudes, respectively.

PMID- 25616640
TI  - Chronic impact of tetracycline on nitrification kinetics and the activity of
      enriched nitrifying microbial culture.
AB  - This study evaluated the chronic impact of tetracycline on biomass with enriched
      nitrifying community sustained in a lab-scale activated sludge system. For this
      purpose, a fill and draw reactor fed with 100 mg COD/L of peptone mixture and 50
      mg N/L of ammonia was sustained at a sludge age of 15 days. At steady-state, the
      reactor operation was continued with a daily tetracycline dosing of 50 mg/L for
      more than 40 days, with periodic monitoring of the microbial composition, the
      nitrifying bacteria abundance, as well as the amoA and 16S rRNA gene activity,
      using molecular techniques. Changes in the kinetics of nitrification were
      quantified by modelling concentration profiles of major nitrogen fractions and
      oxygen uptake rate profiles derived from parallel batch experiments. Activated
      sludge modeling results indicated inhibitory impact of tetracycline on the growth
      of nitrifiers with a significant increase of the half saturation coefficients in
      corresponding rate equations. Tetracycline also inactivated biomass components of
      the enriched culture at a gradually increasing rate with time of exposure,
      leading to total collapse of nitrification. Molecular analyses revealed
      significant changes in the composition of the microbial community throughout the
      observation period. They also showed that continuous exposure to tetracycline
      inflicted significant reduction in amoA mRNA and 16S rRNA levels directly
      affecting nitrification. The chronic impact was much more pronounced on the
      ammonia oxidizing bacteria (AOB) community. These observations explained the
      basis of numerical changes identified in the growth kinetics of nitrifiers under
      stress conditions. 

PMID- 25616641
TI  - Reviewing the evidence: feline diabetic remission.

PMID- 25616642
TI  - Downregulation of the KLF4 transcription factor inhibits the proliferation and
      migration of canine mammary tumor cells.
AB  - Canine mammary tumor (CMT) is the most common neoplasm in female dogs, and over
      50% of CMTs are diagnosed as malignant. Kruppel-like factor 4 (KLF4) is a member
      of the KLF family of transcription factors and is associated with cell
      proliferation, differentiation, migration, and apoptosis. Although the role of
      KLF4 is still controversial in various human cancers, KLF4 has been identified as
      an oncogene in human breast cancer. Moreover, high KLF4 expression is correlated
      with an aggressive phenotype in CMT. Therefore, investigating the function of
      KLF4 may help better understand the pathogenesis of CMT. In this study, partial
      sequences of canine KLF4 and KLF4 expression were identified in various normal
      canine tissues, as well as CMT cells and Madin-Darby canine kidney (MDCK) cells.
      Kenpaullone, a small molecule inhibitor of KLF4, downregulated KLF4 expression in
      CMT cells and reduced CMT cell proliferation, migration, and colony formation in
      soft agar. Kenpaullone treatment induced S and G2/M phase arrest in CMT and MDCK
      cells, and induced death in CMT cells, but not in MDCK cells. It was concluded
      that KLF4 is expressed in various normal canine tissues, and downregulation of
      KLF4 inhibited CMT cell proliferation and migration, and induced cell death. The
      results of this study suggest that KLF4 may represent a suitable therapeutic
      target for CMT therapy.

PMID- 25616643
TI  - Association of the invasion ability of Porphyromonas gingivalis with the severity
      of periodontitis.
AB  - Porphyromonas gingivalis is one of the well-characterized periodontal pathogens
      involved in periodontitis. The invasive and proteolytic activities of P.
      gingivalis clinical isolates have been shown to be associated with heterogenic
      virulence, as determined in a mouse abscess model. The aims of the present study
      were to identify a P. gingivalis strain with a low virulence among clinical
      isolates, based on its invasive ability and cytokine proteolytic activities, and
      to explore the preferential degradation of a certain cytokine by P. gingivalis.
      P. gingivalis ATCC 33277, W50, and 10 clinical isolates were used. After
      incubating bacteria with IL-4, IL-6, IL-10, IL-17A, TNFalpha, IFNgamma, and IL
      1alpha, the amounts of remaining cytokines were determined by ELISA. Invasion
      ability was measured by a flow cytometric invasion assay. There was inter-strain
      variability both in the cytokine proteolytic activities and invasion ability. In
      addition, differential degradation of cytokines by P. gingivalis was observed:
      while IFNgamma and IL-17A were almost completely degraded, inflammatory cytokines
      TNFalpha and IL-1alpha were less susceptible to degradation. Interestingly, the
      invasion index, but not cytokine proteolytic activities, of P. gingivalis had
      strong positive correlations with clinical parameters of subjects who harbored
      the isolates. Therefore, the invasive ability of P. gingivalis is an important
      virulence factor, and the bacterial invasion step may be a good target for new
      therapeutics of periodontitis. 

PMID- 25616645
TI  - Impact of genotype on clinical course in arrhythmogenic right ventricular
      dysplasia/cardiomyopathy-associated mutation carriers.
AB  - AIMS: We sought to determine the influence of genotype on clinical course and
      arrhythmic outcome among arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD/C)-associated mutation carriers. METHODS AND
      RESULTS: Pathogenic mutations in desmosomal and non-desmosomal genes were
      identified in 577 patients (241 families) from USA and Dutch ARVD/C cohorts.
      Patients with sudden cardiac death (SCD)/ventricular fibrillation (VF) at
      presentation (n = 36) were younger (median 23 vs. 36 years; P < 0.001) than those
      presenting with sustained monomorphic ventricular tachycardia (VT). Among 541
      subjects presenting alive, over a mean follow-up of 6 +/- 7 years, 12 (2%)
      patients died, 162 (30%) had sustained VT/VF, 78 (14%) manifested left
      ventricular dysfunction (EF < 55%), 28 (5%) experienced heart failure (HF), and
      10 (2%) required cardiac transplantation. Patients (n = 22; 4%) with >1 mutation
      had significantly earlier occurrence of sustained VT/VF (mean age 28 +/- 12
      years), lower VT-/VF-free survival (P = 0.037), more frequent left ventricular
      dysfunction (29%), HF (19%) and cardiac transplantation (9%) when compared with
      those with only one mutation. Desmoplakin mutation carriers experienced more than
      four-fold occurrence of left ventricular dysfunction (40%) and HF (13%) than PKP2
      carriers. Missense mutation carriers had similar death-/transplant-free survival
      and VT/VF penetrance (P = 0.137) when compared with those with truncating or
      splice site mutations. Men are more likely to be probands (P < 0.001),
      symptomatic (P < 0.001) and have earlier and more severe arrhythmic expression.
      CONCLUSIONS: Presentation with SCD/VF occurs at a significantly younger age when
      compared with sustained monomorphic VT. The genotype of ARVD/C mutation carriers
      impacts clinical course and disease expression. Male sex negatively modifies
      phenotypic expression.

PMID- 25616648
TI  - From the editor.

PMID- 25616647
TI  - A randomised, open label phase III trial with nimotuzumab, an anti-epidermal
      growth factor receptor monoclonal antibody in the treatment of newly diagnosed
      adult glioblastoma.
AB  - PURPOSE: A randomised, open label phase III trial was conducted to evaluate
      efficacy of nimotuzumab, a monoclonal antibody against epidermal growth factor
      receptor (EGF-R) added to standard therapy for newly diagnosed glioblastoma.
      PATIENTS AND METHODS: 149 glioblastoma patients stratified as with or without
      residual tumour were randomly assigned to receive either intravenous nimotuzumab
      400mg weekly added to standard radiochemotherapy followed by 400mg biweekly after
      twelve weeks or standard radiochemotherapy. Progression status after 52 weeks
      (12moPFS) and progression-free survival (PFS) based on Macdonald criteria were co
      primary and overall survival (OS), toxicity and quality of life secondary end
      points. RESULTS: 142 patients were evaluated for efficacy (per protocol cohort).
      12 moPFS was 25.6% in the experimental arm and 20.3% in the control group. In
      residual tumour patients (n=81) median PFS was 5.6 versus 4.0 months, (hazard
      ratio (HR), 0.87; 95% confidence interval (CI), 0.55-1.37), for patients without
      residual tumour (n=61) it was 10.6 versus 9.9 months, (HR, 1.01; 95% CI, 0.57
      1.77). Median OS in patients with residual tumour was 19.5 versus 16.7 months,
      (HR, 0.90; 95% CI, 0.52-1.57; P=0.7061), for patients without 23.3 versus 21.0
      months (HR, 0.77; 95% CI, 0.41-1.44; P=0.4068). A small cohort of MGMT non
      methylated patients with residual tumour showed PFS of 6.2 versus 4.0 months (HR,
      0.77; 95% CI, 0.35-1.67; P=0.4997) and OS of 19.0 versus 13.8 months (HR, 0.66;
      95% CI, 0.27-1.64; P=0.3648). EGF-R amplification did not correlate with clinical
      efficacy of nimotuzumab. Nimotuzumab was well tolerated. CONCLUSION: This study,
      albeit negative, contains hypothesis generating signals supporting evaluation of
      correlative, efficacy-predicting tumour parameters for nimotuzumab in the
      treatment of glioblastoma.

PMID- 25616650
TI  - The wire anchor loop traction (WALT) maneuver.
AB  - Crossing the neck of large complex intracranial aneurysms for the purposes of
      stent deployment can be challenging using standard over the wire techniques. We
      describe a novel yet simple technique for straightening out the loop formed
      within a large intracranial aneurysm, which is often required in order to cross
      the aneurysm neck into the distal branch. Both the microcatheter and microwire
      are initially introduced into the distal vasculature, followed by withdrawal of
      the microwire to a point parallel to the distal exiting branch. The microcatheter
      and microwire are then gently withdrawn and a series of maneuvers to gradually
      reduce the loop is performed, obviating the need for distal purchase in the form
      of a stent, balloon, or coil, which have previously been described to maintain
      distal purchase. 

PMID- 25616649
TI  - Plant trait expression responds to establishment timing.
AB  - Trait divergence between co-occurring individuals could decrease the strength of
      competition between these individuals, thus promoting their coexistence. To test
      this hypothesis, we manipulated establishment timing for four congeneric pairs of
      perennial plants and assessed trait plasticity. Because soil conditions can
      affect trait expression and competition, we grew the plants in field-collected
      soil from each congener. Competition was generally weak across species, but the
      order of establishment affected divergence in biomass between potmates for three
      congeneric pairs. The type of plastic response differed among genera, with trait
      means of early-establishing individuals of Rumex and Solanum spp. differing from
      late-establishing individuals, and trait divergence between potmates of Plantago
      and Trifolium spp. depending on which species established first. Consistent with
      adaptive trait plasticity, higher specific leaf area (SLA) and root-shoot ratio
      in Rumex spp. established later suggest that these individuals were maximizing
      their ability to capture light and soil resources. Greater divergence in SLA
      correlated with increased summed biomass of competitors, which is consistent with
      trait divergence moderating the strength of competition for some species. Species
      did not consistently perform better in conspecific or congener soil, but soil
      type influenced the effect of establishment order. For example, biomass
      divergence between Rumex potmates was greater in R. obtusifolius soil regardless
      of which species established first. These results suggest that plant responses to
      establishment timing act in a species-specific fashion, potentially enhancing
      coexistence in plant communities. 

PMID- 25616646
TI  - ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12
      months of clopidogrel therapy after drug-eluting stenting.
AB  - BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel
      therapy after drug-eluting stent (DES) implantation remains unclear. METHODS:
      This multicentre, randomized, double-blind, placebo-controlled trial tested the
      hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel
      is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES
      implantation, patients on clopidogrel were randomly assigned to either a 6-month
      period of placebo or an additional 6-month period of clopidogrel. The primary
      endpoint was the composite of death, myocardial infarction, stent thrombosis,
      stroke, and thrombolysis in myocardial infarction major bleeding at 9 months
      after randomization. RESULTS: Owing to slow recruitment and low event rates, the
      trial was stopped prematurely after enrolment of 4005 of 6000 planned patients.
      Of 4000 patients included in the final analysis, 1997 received 6 months of
      clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29
      patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%)
      assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95%
      confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority
      <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6
      months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard
      ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial
      infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months
      clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21
      2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event
      rates, we did not observe a significant difference in net clinical outcome
      between 6 and 12 months of clopidogrel therapy after DES implantation. However,
      the results of the trial must be considered in view of its premature termination
      and lower than expected event rates. The trial is registered with
      ClinicalTrials.gov, Identifier: NCT00661206.

PMID- 25616644
TI  - Differing prognostic value of pulse pressure in patients with heart failure with
      reduced or preserved ejection fraction: results from the MAGGIC individual
      patient meta-analysis.
AB  - AIMS: Low pulse pressure is a marker of adverse outcome in patients with heart
      failure (HF) and reduced ejection fraction (HF-REF) but the prognostic value of
      pulse pressure in patients with HF and preserved ejection fraction (HF-PEF) is
      unknown. We examined the prognostic value of pulse pressure in patients with HF
      PEF [ejection fraction (EF) >= 50%] and HF-REF. METHODS AND RESULTS: Data from 22
      HF studies were examined. Preserved left ventricular ejection fraction (LVEF) was
      defined as LVEF >= 50%. All-cause mortality at 3 years was evaluated in 27 046
      patients: 22 038 with HF-REF (4980 deaths) and 5008 with HF-PEF (828 deaths).
      Pulse pressure was analysed in quintiles in a multivariable model adjusted for
      the previously reported Meta-Analysis Global Group in Chronic Heart Failure
      prognostic variables. Heart failure and reduced ejection fraction patients in the
      lowest pulse pressure quintile had the highest crude and adjusted mortality risk
      (adjusted hazard ratio 1.68, 95% confidence interval 1.53-1.84) compared with all
      other pulse pressure groups. For patients with HF-PEF, higher pulse pressure was
      associated with the highest crude mortality, a gradient that was eliminated after
      adjustment for other prognostic variables. CONCLUSION: Lower pulse pressure
      (especially <53 mmHg) was an independent predictor of mortality in patients with
      HF-REF, particularly in those with an LVEF < 30% and systolic blood pressure <140
      mmHg. Overall, this relationship between pulse pressure and outcome was not
      consistently observed among patients with HF-PEF.

PMID- 25616651
TI  - Total testosterone levels are often more than three times elevated in patients
      with androgen-secreting tumours.
AB  - Hirsutism is present in up to 25% reproductive aged women and is most often
      caused by polycystic ovary syndrome. Less than 5% of patients with hirsutism are
      diagnosed with rare endocrine diseases including ovarian or adrenal androgen
      producing tumours, but these tumours may be malignant and need surgery. Terminal
      hair growth on lip and chin gradually increases after menopause, which
      complicates distinction from normal physiological variation. Precise testosterone
      assays have just recently become available in the daily clinic. We present three
      women diagnosed with testosterone-producing tumours. Gold standard techniques
      were used to measure testosterone levels. All tumours originated from the
      ovaries. Based on the present cases and the existing literature, we suggest that
      androgen-producing tumours should be suspected in patients with rapid progression
      of hyperandrogen symptoms, particularly when total testosterone levels are above
      three times the upper reference limit. 

PMID- 25616652
TI  - Long-term efficacy of deep sclerectomy in Posner-Schlossman syndrome.
AB  - The Posner-Schlossman syndrome (PSS) is an elusive disease that can lead to
      serious consequences such as glaucomatous damage. Deep sclerectomy has been
      proven thus far to be the most effective surgical intervention to keep
      intraocular pressure (IOP) elevation under control compared with other surgical
      techniques, because it presents the least amount of postoperative complications.
      The aim of this case report is to demonstrate the efficacy of deep sclerectomy
      with T-Flux and the long-lasting effects that persist after 7 years in an eye
      affected by PSS. This case report demonstrates that an intervention of deep
      sclerectomy can lead to excellent results in terms of visual acuity as well as
      IOP lowering early in the history of the patient affected by PSS so that it can
      preclude establishment of glaucomatous damage. 

PMID- 25616653
TI  - Outcome of central hypoventilation secondary to childhood pertussis encephalitis
      in adulthood.
AB  - We present a rare case of central hypoventilation secondary to pertussis
      encephalopathy occurring during childhood. The patient was successfully managed
      by negative pressure ventilation initially until portable non-invasive
      ventilators became available. The patient was, unfortunately, lost to follow-up.
      She was reviewed in adulthood following several years of non-compliance to
      treatment and found asymptomatic despite chronic hypercapnoea. 

PMID- 25616654
TI  - Deep colonic endoscopic submucosal dissection using a modified clip and snare
      method incorporating a pre-looping technique.
AB  - Endoscopic submucosal dissection (ESD) is more difficult to perform for
      colorectal cancer than for early gastric cancer. The use of traction to
      facilitate direct submucosal layer visualisation is promising in reducing the
      procedure's time and complication rate. We report a case in which deep colonic
      ESD was performed with a modified clip and snare method. A 57-year-old man was
      admitted for ESD of a laterally spreading caecal lesion 25 mm in size (classified
      as LST-GM) that had been found on colonoscopy. The clip and snare method was
      previously developed for ESD of gastric cancer; we improved on this method and
      applied our pre-looping technique in the deep colon. The procedure lasted 40 min
      and was without complications. Our pre-looping technique represents a
      modification of the clip and snare method, enabling its performance in the deep
      colon. We expect that our technique will be applicable to colorectal tumours. 

PMID- 25616655
TI  - Expansive pulmonary artery aneurysm in an IV drug user.

PMID- 25616656
TI  - Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in
      pregnancy.
AB  - BCR-ABL inhibitors administered in conjunction with chemotherapy have
      significantly improved outcomes in Philadelphia chromosome-positive acute
      lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on
      risks to the fetus are limited. We report a woman treated with chemotherapy and
      imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss
      available data. 

PMID- 25616657
TI  - Temozolomide retreatment in a recurrent prolactin-secreting pituitary adenoma:
      Hormonal and radiographic response.
AB  - BACKGROUND: Temozolomide is an oral alkylating agent with schedule-dependent
      antitumor activity against high-grade malignancies including high-grade glioma.
      Increasingly, reports have suggested that temozolomide may have activity as a
      salvage therapy for aggressive, recurrent pituitary adenomas or carcinomas that
      fail surgery, radiation and other pharmacotherapy. To our knowledge, temozolomide
      retreatment following initial responsiveness has not previously been
      demonstrated. CASE REPORT: A woman was diagnosed with a prolactin-secreting
      pituitary adenoma in 1995 (age 44). Despite bromocriptine therapy, transphenoidal
      resection, radiotherapy, and cabergoline treatment she experienced continued
      clinico-radiographic progression, and temozolomide was initiated in 2011. She
      received three treatment cycles with rapid, dramatic clinico-radiographic
      response, and 99.3% reduction in serum prolactin. After three years of close
      observation, she developed recurrent radiographic progression and prolactin
      elevation. She was re-initiated on temozolomide, and after four cycles, clinical,
      radiographic and hormonal response was observed with a 92.2% reduction in serum
      prolactin. CONCLUSIONS/SUMMARY: Temozolomide is an increasingly described
      treatment option for refractory pituitary adenomas and carcinomas. In the current
      report, we document rapid biochemical response following retreatment with
      temozolomide in aggressive pituitary adenoma. When "off label" salvage therapy
      with temozolomide is offered for patients with recurrent prolactinomas,
      retreatment at the time of recurrence can be considered.

PMID- 25616658
TI  - Decisional capacity and medication adherence among youth with HIV.
AB  - This exploratory study examined the degree to which decisional capacity (DC) is
      associated with measures of self-reported medication adherence. We hypothesized
      that youth with higher levels of DC would report greater levels of antiretroviral
      medication adherence. Seventy-two (72) youth with HIV aged 13-24 participated in
      this study. Data collection included administration of the MacArthur Competence
      Tool for Treatment and measures of adherence (i.e., seven-day self-report
      interview, visual analog scale, and biological indicators). Data were analyzed
      using descriptive statistics, intercorrelations, and multiple and Poisson
      regression analyses. Youth with HIV who exhibited greater understanding of their
      disease were more likely to report fewer missed doses in the last seven days.
      Findings build upon literature in the areas of DC and health literacy and
      highlight the potential utility of enhancing HIV disease understanding among
      youth with HIV. 

PMID- 25616659
TI  - Association between depression and nonadherence to antiretroviral therapy in
      pregnant women with perinatally acquired HIV.
AB  - Women with perinatally acquired HIV (PAH) face unique psychosocial challenges due
      to the presence of a lifelong chronic illness and often unstable living
      situations. With advances in HIV treatment, an increasing number of those with
      PAH are reaching childbearing age and becoming pregnant. Depression may be an
      important and common factor that complicates both treatment and pregnancy
      outcomes in this group. We conducted a retrospective cohort study in pregnant
      patients with PAH to determine if history of depression is associated with
      nonadherence to antiretroviral therapy (ART). We reviewed charts of women with
      PAH receiving prenatal care at a single institution from March 1995 to December
      2012. ART nonadherence was measured by patient self-report of any missed doses in
      the third trimester. Demographic, obstetric, and HIV infection characteristics of
      patients with a history of depression (dPAH) were compared to patients without a
      history of depression. Nine pregnancies among 6 dPAH women and 14 pregnancies
      among 12 PAH women without a history of depression were identified. None of the
      dPAH women reported 100% adherence to ART in the third trimester while 57% of
      women without a history of depression reported strict adherence (p = 0.04). The
      mean HIV RNA level at delivery was higher among dPAH women (17,399 vs. 2966
      copies/Ml; p = 0.03) and fewer reached an undetectable HIV RNA level (<400
      copies/mL) at delivery (p = 0.03). We concluded that a history of depression may
      contribute to poor medication adherence and treatment outcomes among pregnant
      women with PAH. Focused attention on diagnosis and treatment of depression in the
      preconception period may lead to more optimal medication adherence. 

PMID- 25616660
TI  - Intracellular screening of a peptide library to derive a potent peptide inhibitor
      of alpha-synuclein aggregation.
AB  - Aggregation of alpha-synuclein (alpha-syn) into toxic fibrils is a pathogenic
      hallmark of Parkinson disease (PD). Studies have focused largely on residues 71
      82, yet most early-onset mutations are located between residues 46 and 53. A
      semirationally designed 209,952-member library based entirely on this region was
      constructed, containing all wild-type residues and changes associated with early
      onset PD. Intracellular cell survival screening and growth competition isolated a
      10-residue peptide antagonist that potently inhibits alpha-syn aggregation and
      associated toxicity at a 1:1 stoichiometry. This was verified using continuous
      growth measurements and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide cytotoxicity studies. Atomic force microscopy and circular dichroism on
      the same samples showed a random-coil structure and no oligomers. A new region of
      alpha-syn for inhibitor targeting has been highlighted, together with the
      approach of using a semirational design and intracellular screening. The peptides
      can then be used as candidates for modification in drugs capable of slowing or
      even preventing the onset of PD. 

PMID- 25616661
TI  - Evaluating the role of retinal membrane guanylyl cyclase 1 (RetGC1) domains in
      binding guanylyl cyclase-activating proteins (GCAPs).
AB  - Retinal membrane guanylyl cyclase 1 (RetGC1) regulated by guanylyl cyclase
      activating proteins (GCAPs) controls photoreceptor recovery and when mutated
      causes blinding disorders. We evaluated the principal models of how GCAP1 and
      GCAP2 bind RetGC1: through a shared docking interface versus independent binding
      sites formed by distant portions of the cyclase intracellular domain. At near
      saturating concentrations, GCAP1 and GCAP2 activated RetGC1 from HEK293 cells and
      RetGC2(-/-)GCAPs1,2(-/-) mouse retinas in a non-additive fashion. The M26R GCAP1,
      which binds but does not activate RetGC1, suppressed activation of recombinant
      and native RetGC1 by competing with both GCAP1 and GCAP2. Untagged GCAP1
      displaced both GCAP1-GFP and GCAP2-GFP from the complex with RetGC1 in HEK293
      cells. The intracellular segment of a natriuretic peptide receptor A guanylyl
      cyclase failed to bind GCAPs, but replacing its kinase homology and dimerization
      domains with those from RetGC1 restored GCAP1 and GCAP2 binding by the hybrid
      cyclase and its GCAP-dependent regulation. Deletion of the Tyr(1016)-Ser(1103)
      fragment in RetGC1 did not block GCAP2 binding to the cyclase. In contrast,
      substitutions in the kinase homology domain, W708R and I734T, linked to Leber
      congenital amaurosis prevented binding of both GCAP1-GFP and GCAP2-GFP. Our
      results demonstrate that GCAPs cannot regulate RetGC1 using independent primary
      binding sites. Instead, GCAP1 and GCAP2 bind with the cyclase molecule in a
      mutually exclusive manner using a common or overlapping binding site(s) in the
      Arg(488)-Arg(851) portion of RetGC1, and mutations in that region causing Leber
      congenital amaurosis blindness disrupt activation of the cyclase by both GCAP1
      and GCAP2. 

PMID- 25616662
TI  - Centrobin-mediated regulation of the centrosomal protein 4.1-associated protein
      (CPAP) level limits centriole length during elongation stage.
AB  - Microtubule-based centrioles in the centrosome mediate accurate bipolar cell
      division, spindle orientation, and primary cilia formation. Cellular checkpoints
      ensure that the centrioles duplicate only once in every cell cycle and achieve
      precise dimensions, dysregulation of which results in genetic instability and
      neuro- and ciliopathies. The normal cellular level of centrosomal protein 4.1
      associated protein (CPAP), achieved by its degradation at mitosis, is considered
      as one of the major mechanisms that limits centriole growth at a predetermined
      length. Here we show that CPAP levels and centriole elongation are regulated by
      centrobin. Exogenous expression of centrobin causes abnormal elongation of
      centrioles due to massive accumulation of CPAP in the cell. Conversely, CPAP was
      undetectable in centrobin-depleted cells, suggesting that it undergoes
      degradation in the absence of centrobin. Only the reintroduction of full-length
      centrobin, but not its mutant form that lacks the CPAP binding site, could
      restore cellular CPAP levels in centrobin-depleted cells, indicating that
      persistence of CPAP requires its interaction with centrobin. Interestingly,
      inhibition of the proteasome in centrobin-depleted cells restored the cellular
      and centriolar CPAP expression, suggesting its ubiquitination and proteasome
      mediated degradation when centrobin is absent. Intriguingly, however, centrobin
      overexpressing cells also showed proteasome-independent accumulation of
      ubiquitinated CPAP and abnormal, ubiquitin-positive, elongated centrioles.
      Overall, our results show that centrobin interacts with ubiquitinated CPAP and
      prevents its degradation for normal centriole elongation function. Therefore, it
      appears that loss of centrobin expression destabilizes CPAP and triggers its
      degradation to restrict the centriole length during biogenesis. 

PMID- 25616663
TI  - Evidence of a structural and functional ammonium transporter RhBG.anion exchanger
      1.ankyrin-G complex in kidney epithelial cells.
AB  - The renal ammonium transporter RhBG and anion exchanger 1 kAE1 colocalize in the
      basolateral domain of alpha-intercalated cells in the distal nephron. Although we
      have previously shown that RhBG is linked to the spectrin-based skeleton through
      ankyrin-G and that its NH3 transport activity is dependent on this association,
      there is no evidence for an interaction of kAE1 with this adaptor protein. We
      report here that the kAE1 cytoplasmic N terminus actually binds to ankyrin-G,
      both in yeast two-hybrid analysis and by coimmunoprecipitation in situ in HEK293
      cells expressing recombinant kAE1. A site-directed mutagenesis study allowed the
      identification of three dispersed regions on kAE1 molecule linking the third and
      fourth repeat domains of ankyrin-G. One secondary docking site corresponds to a
      major interacting loop of the erythroid anion exchanger 1 (eAE1) with ankyrin-R,
      whereas the main binding region of kAE1 does not encompass any eAE1 determinant.
      Stopped flow spectrofluorometry analysis of recombinant HEK293 cells revealed
      that the Cl(-)/HCO3 (-) exchange activity of a kAE1 protein mutated on the
      ankyrin-G binding site was abolished. This disruption impaired plasma membrane
      expression of kAE1 leading to total retention on cytoplasmic structures in
      polarized epithelial Madin-Darby canine kidney cell transfectants. kAE1 also
      directly interacts with RhBG without affecting its surface expression and NH3
      transport function. This is the first description of a structural and functional
      RhBG.kAE1.ankyrin-G complex at the plasma membrane of kidney epithelial cells,
      comparable with the well known Rh.eAE1.ankyrin-R complex in the red blood cell
      membrane. This renal complex could participate in the regulation of acid-base
      homeostasis. 

PMID- 25616664
TI  - Autophagy enhances intestinal epithelial tight junction barrier function by
      targeting claudin-2 protein degradation.
AB  - Autophagy is an intracellular degradation pathway and is considered to be an
      essential cell survival mechanism. Defects in autophagy are implicated in many
      pathological processes, including inflammatory bowel disease. Among the innate
      defense mechanisms of intestinal mucosa, a defective tight junction (TJ) barrier
      has been postulated as a key pathogenic factor in the causation and progression
      of inflammatory bowel disease by allowing increased antigenic permeation. The
      cross-talk between autophagy and the TJ barrier has not yet been described. In
      this study, we present the novel finding that autophagy enhances TJ barrier
      function in Caco-2 intestinal epithelial cells. Nutrient starvation-induced
      autophagy significantly increased transepithelial electrical resistance and
      reduced the ratio of sodium/chloride paracellular permeability. Nutrient
      starvation reduced the paracellular permeability of small-sized urea but not
      larger molecules. The role of autophagy in the modulation of paracellular
      permeability was confirmed by pharmacological induction as well as
      pharmacological and genetic inhibition of autophagy. Consistent with the
      autophagy-induced reduction in paracellular permeability, a marked decrease in
      the level of the cation-selective, pore-forming TJ protein claudin-2 was observed
      after cell starvation. Starvation reduced the membrane presence of claudin-2 and
      increased its cytoplasmic, lysosomal localization. Therefore, our data show that
      autophagy selectively reduces epithelial TJ permeability of ions and small
      molecules by lysosomal degradation of the TJ protein claudin-2. 

PMID- 25616665
TI  - MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal
      cancer.
AB  - Development of drug resistance is one of the major causes of colorectal cancer
      recurrence, yet mechanistic understanding and therapeutic options remain limited.
      Here, we show that expression of microRNA (miR)-520g is correlated with drug
      resistance of colon cancer cells. Ectopic expression of miR-520g conferred
      resistance to 5-fluorouracil (5-FU)- or oxaliplatin-induced apoptosis in vitro
      and reduced the effectiveness of 5-FU in the inhibition of tumor growth in a
      mouse xenograft model in vivo. Further studies indicated that miR-520g mediated
      drug resistance through down-regulation of p21 expression. Moreover, p53
      suppressed miR-520g expression, and deletion of p53 up-regulated miR-520g
      expression. Inhibition of miR-520g in p53(-/-) cells increased their sensitivity
      to 5-FU treatment. Importantly, studies of patient samples indicated that
      expression of miR-520g correlated with chemoresistance in colorectal cancer.
      These findings indicate that the p53/miR-520g/p21 signaling axis plays an
      important role in the response of colorectal cancer to chemotherapy. A major
      implication of our studies is that inhibition of miR-520g or restoration of p21
      expression may have considerable therapeutic potential to overcome drug
      resistance in colorectal cancer patients, especially in those with mutant p53. 

PMID- 25616666
TI  - Differential contributions of the outer membrane receptors PhuR and HasR to heme
      acquisition in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa PAO1 encodes two outer membrane receptors, PhuR
      (Pseudomonas heme uptake) and HasR (heme assimilation system). The HasR and PhuR
      receptors have distinct heme coordinating ligands and substrate specificities.
      HasR is encoded in an operon with a secreted hemophore, HasAp. In contrast the
      non-hemophore-dependent PhuR is encoded within an operon along with proteins
      required for heme translocation into the cytoplasm. Herein we report on the
      contributions of the HasR and PhuR receptors to heme uptake and utilization.
      Employing bacterial genetics and isotopic [(13)C]heme labeling studies we have
      shown both PhuR and HasR are required for optimal heme utilization. However, the
      unique His-Tyr-ligated PhuR plays a major role in the acquisition of heme. In
      contrast the HasR receptor plays a primary role in the sensing of extracellular
      heme and a supplementary role in heme uptake. We propose PhuR and HasR represent
      non-redundant heme receptors, capable of accessing heme across a wide range of
      physiological conditions on colonization of the host. 

PMID- 25616668
TI  - Aleksander Luria and diaschisis.

PMID- 25616669
TI  - Reply: Aleksander Luria and diaschisis.

PMID- 25616670
TI  - Dropping out of Ethiopia's community-based health insurance scheme.
AB  - Low contract renewal rates have been identified as one of the challenges facing
      the development of community-based health insurance (CBHI) schemes. This article
      uses longitudinal household survey data gathered in 2012 and 2013 to examine
      dropout in the case of Ethiopia's pilot CBHI scheme. We treat dropout as a
      function of scheme affordability, health status, scheme understanding and quality
      of care. The scheme saw enrolment increase from 41% 1 year after inception to 48%
      a year later. An impressive 82% of those who enrolled in the first year renewed
      their subscriptions, while 25% who had not enrolled joined the scheme. The
      analysis shows that socioeconomic status, a greater understanding of health
      insurance and experience with and knowledge of the CBHI scheme are associated
      with lower dropout rates. While there are concerns about the quality of care and
      the treatment meted out to the insured by providers, the overall picture is that
      returns from the scheme are overwhelmingly positive. For the bulk of households,
      premiums do not seem to be onerous, basic understanding of health insurance is
      high and almost all those who are currently enrolled signalled their desire to
      renew contracts. 

PMID- 25616671
TI  - The Clinical and Cost Effectiveness of Aflibercept in Combination with Irinotecan
      and Fluorouracil-Based Therapy (FOLFIRI) for the Treatment of Metastatic
      Colorectal Cancer Which has Progressed Following Prior Oxaliplatin-Based
      Chemotherapy: a Critique of the Evidence.
AB  - The National Institute for Health and Care Excellence (NICE) invited the
      manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness
      evidence for aflibercept in combination with irinotecan and fluorouracil-based
      therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of
      metastatic colorectal cancer which has progressed following prior oxaliplatin
      based chemotherapy, as part of the Institute's Single Technology Appraisal
      process. The Centre for Reviews and Dissemination and Centre for Health Economics
      at the University of York were commissioned to act as the independent Evidence
      Review Group (ERG). This article provides a description of the company
      submission, the ERG review and the resulting NICE guidance TA307 issued in March
      2014. The ERG critically reviewed the evidence presented in the manufacturer's
      submission and identified areas requiring clarification, for which the
      manufacturer provided additional evidence. The clinical effectiveness data were
      derived from one good-quality double-blind randomised controlled trial (RCT), the
      VELOUR trial, which compared aflibercept plus FOLFIRI with placebo plus FOLFIRI.
      This RCT found a small but statistically significant increase in overall survival
      (OS); the difference in median OS was 1.44 months (13.5 months in the aflibercept
      group and 12.06 months in the placebo group). There was also a statistically
      significant increase in progression-free survival (PFS) with aflibercept; the
      difference in median PFS was 2.23 months (6.9 months in the aflibercept group and
      4.67 months in the placebo group). However, grade 3-4 adverse events were more
      frequent in the aflibercept group than the placebo group: 83.5% compared with
      62.5%. Treatment-emergent adverse events led to permanent discontinuation of
      treatment in 26.8% of patients in the aflibercept group and 12.1% of patients in
      the placebo group. The manufacturer's submission included an estimation of mean
      OS benefit based on extrapolation of the data, which was considerably longer than
      the median OS benefit reported (4.7 vs. 1.44 months). The ERG considered this to
      be an over estimate. The base-case incremental cost-effectiveness ratio (ICER)
      for the overall population was reported by the manufacturer to be L36,294 per
      quality-adjusted life-year (QALY). After correcting the model programming and
      updating the model to include the ERG's preferred parameter estimates, the ICER
      from the ERG's alternative base case was L54,368 per QALY. The extrapolation of
      the OS curves was the key cost-effectiveness driver and a major source of
      uncertainty in the model. Additional scenarios related to the extrapolation of OS
      undertaken by the ERG resulted in ICERs between L62,894 and L92,089 per QALY.
      After consideration of the manufacturer's submission and the ERG's critique, and
      submissions from other stakeholders, the NICE Appraisal Committee concluded that
      aflibercept in combination with irinotecan and fluorouracil-based therapy could
      not be considered a cost effective use of National Health Service resources for
      treating metastatic colorectal cancer that is resistant to or has progressed
      after an oxaliplatin-containing regimen. Aflibercept in combination with
      irinotecan and fluorouracil-based therapy is not recommended for the treatment of
      metastatic colorectal cancer that is resistant to or has progressed after an
      oxaliplatin-containing regimen in NICE guidance TA307.

PMID- 25616672
TI  - Central autonomic nervous system response to autonomic challenges is altered in
      patients with a previous episode of Takotsubo cardiomyopathy.
AB  - AIMS: Takotsubo cardiomyopathy is an intriguing disease characterized by acute
      transient left ventricular dysfunction usually triggered by an episode of severe
      stress. The excessive levels of catecholamines and the overactivation of the
      sympathetic system are believed to be the main pathophysiologic mechanisms of
      Takotsubo cardiomyopathy, but it is unclear whether there is a structural or
      functional signature of the disease. In this sense, our aim was to characterize
      the central autonomic system response to autonomic challenges in patients with a
      previous episode of Takotsubo cardiomyopathy when compared with a control group
      of healthy volunteers. METHODS AND RESULTS: Functional magnetic resonance imaging
      (fMRI) was performed in four patients with a previous episode of Takotsubo
      cardiomyopathy (average age of 67 +/- 12 years) and in eight healthy volunteers
      (average age of 66 +/- 5 years) while being submitted to different autonomic
      challenges (cold exposure and Valsalva manoeuvre). The fMRI analysis revealed a
      significant variation of the blood oxygen level dependent signal triggered by the
      Valsalva manoeuvre in specific areas of the brain involved in the cortical
      control of the autonomic system and significant differences in the pattern of
      activation of the insular cortex, amygdala and the right hippocampus between
      patients with Takotsubo cardiomyopathy and controls, even though these regions
      did not present significant volumetric changes. CONCLUSION: The central autonomic
      response to autonomic challenges is altered in patients with Takotsubo
      cardiomyopathy, thus suggesting a dysregulation of the central autonomic nervous
      system network. Subsequent studies are needed to unveil whether these alterations
      are causal or predisposing factors to Takotsubo cardiomyopathy.

PMID- 25616673
TI  - Accounting for behavioral responses during a flu epidemic using home television
      viewing.
AB  - BACKGROUND: Theory suggests that individual behavioral responses impact the
      spread of flu-like illnesses, but this has been difficult to empirically
      characterize. Social distancing is an important component of behavioral response,
      though analyses have been limited by a lack of behavioral data. Our objective is
      to use media data to characterize social distancing behavior in order to
      empirically inform explanatory and predictive epidemiological models. METHODS: We
      use data on variation in home television viewing as a proxy for variation in time
      spent in the home and, by extension, contact. This behavioral proxy is imperfect
      but appealing since information on a rich and representative sample is collected
      using consistent techniques across time and most major cities. We study the April
      May 2009 outbreak of A/H1N1 in Central Mexico and examine the dynamic behavioral
      response in aggregate and contrast the observed patterns of various demographic
      subgroups. We develop and calibrate a dynamic behavioral model of disease
      transmission informed by the proxy data on daily variation in contact rates and
      compare it to a standard (non-adaptive) model and a fixed effects model that
      crudely captures behavior. RESULTS: We find that after a demonstrable initial
      behavioral response (consistent with social distancing) at the onset of the
      outbreak, there was attenuation in the response before the conclusion of the
      public health intervention. We find substantial differences in the behavioral
      response across age subgroups and socioeconomic levels. We also find that the
      dynamic behavioral and fixed effects transmission models better account for
      variation in new confirmed cases, generate more stable estimates of the baseline
      rate of transmission over time and predict the number of new cases over a short
      horizon with substantially less error. CONCLUSIONS: Results suggest that A/H1N1
      had an innate transmission potential greater than previously thought but this was
      masked by behavioral responses. Observed differences in behavioral response
      across demographic groups indicate a potential benefit from targeting social
      distancing outreach efforts.

PMID- 25616674
TI  - The perfect reduction: approaches and techniques.
AB  - Anatomic reduction of femoral neck fractures is difficult to obtain in a closed
      fashion. Open reduction provides for direct and controlled manipulation of
      fracture fragments. This can be accomplished via multiple approaches. The
      anterolateral, or Watson-Jones, approach or Smith-Petersen, or direct anterior,
      approach are the two most frequently used. Percutaneous techniques have also been
      described, though they lack the visual confirmation of reduction of a traditional
      open approach. These can be performed using a fracture table or with a free leg
      on a radiolucent table in either supine or lateral positions. Knowledge of the
      hip and pelvis anatomy is crucial for the preservation of critical femoral neck
      vasculature. Intra-operative fluoroscopy together with direct visualization
      provides the framework for successful manipulation of the fracture fragments,
      temporary stabilization, and ultimately fracture fixation. 

PMID- 25616667
TI  - Genetic variants are major determinants of CSF antibody levels in multiple
      sclerosis.
AB  - Immunological hallmarks of multiple sclerosis include the production of
      antibodies in the central nervous system, expressed as presence of oligoclonal
      bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in
      the cerebrospinal fluid compared to serum. However, the underlying differences
      between oligoclonal band-positive and -negative patients with multiple sclerosis
      and reasons for variability in immunoglobulin G index are not known. To identify
      genetic factors influencing the variation in the antibody levels in the
      cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide
      association screen in patients collected from nine countries for two traits,
      presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index
      levels (n = 938), followed by a replication in 3891 additional patients. We
      replicate previously suggested association signals for oligoclonal band status in
      the major histocompatibility complex region for the rs9271640*A-rs6457617*G
      haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA
      DQA1*0301 (P comparing two haplotypes = 8.88 * 10(-16)). Furthermore, we identify
      a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for
      oligoclonal band status (P = 8.45 * 10(-7)). The previously reported association
      of the immunoglobulin heavy chain locus with immunoglobulin G index reaches
      strong evidence for association in this data set (P = 3.79 * 10(-37)). We
      identify two novel associations in the major histocompatibility complex region
      with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 *
      10(-22)), shared with oligoclonal band status, and an additional independent
      effect of rs6457617*G (P = 3.68 * 10(-6)). Variants identified in this study
      account for up to 2-fold differences in the odds of being oligoclonal band
      positive and 7.75% of the variation in immunoglobulin G index. Both traits are
      associated with clinical features of disease such as female gender, age at onset
      and severity. This is the largest study population so far investigated for the
      genetic influence on antibody levels in the cerebrospinal fluid in multiple
      sclerosis, including 6950 patients. We confirm that genetic factors underlie
      these antibody levels and identify both the major histocompatibility complex and
      immunoglobulin heavy chain region as major determinants. 

PMID- 25616675
TI  - Timing of internal fixation of femoral neck fractures. A systematic review and
      meta-analysis of the final outcome.
AB  - The aim of the present study was to evaluate the effect of timing of internal
      fixation of intracapsular fractures of the neck of femur on the development of
      late complications, particularly osteonecrosis of femoral head (ONFH) and non
      union. We undertook a systematic review of the literature adhering to the PRISMA
      guidelines. There were 7 eligible reports for the final analysis. The
      methodological quality of component studies was assessed with the Coleman
      Methodology Score (CMS). Each included study was assigned a score independently
      by the two reviewers. The final score of each individual study constituted the
      average value of the scores given by the two reviewers. The agreement between the
      two assessors was tested with intraclass correlation coefficient (ICC). The CMS
      ranged from 37 to 64 within component studies (mean: 46.5, SD: 10.8, median: 41).
      The ICC was 0.94 (95% CI: 0.69-0.99), implying a nearly perfect agreement between
      the two assessors. Based on the available data regarding the timing of operative
      fixation of the femoral neck fractures, 4 discreet pairs of comparison groups
      could be created: (1) fractures fixed within 6h from injury versus fractures
      fixed after 6h from injury; (2) fractures fixed within 12h versus after 12h; (3)
      fractures fixed within 24h versus after 24h; and (4) fractures fixed within 6h
      versus after 24h. Outcome measures were analyzed within each one of the above
      pairs of treatment groups. The following subgroups analyses were a priori
      decided: (1) initial fracture displacement (displaced vs. undisplaced fractures);
      (2) fixation method (cannulated screws vs. sliding hip screw); (3) quality of
      reduction (anatomic vs non-anatomic reduction). This study failed to prove any
      essential association between timing of NOF fracture internal fixation and
      incidence of AVN. With respect to non-union though, it indicated that delay of
      internal fixation of more than 24h could increase substantially the odds of non
      union. 

PMID- 25616676
TI  - Temporal changes of spinal subarachnoid space patency after graded spinal cord
      injury in rats.
AB  - INTRODUCTION: Disturbances in spinal subarachnoid space (SSAS) patency after SCI
      have been reported as an incidental finding, but there is a lack of information
      on its in vivo extent and time course. For substances and cells carried in the
      cerebrospinal fluid (CSF) to reach damaged neural tissue and promote reparative
      processes, CSF must be able to flow freely in SASS. OBJECTIVE: To characterise
      the extent and time course of SSAS patency disruption in vivo in a rat model
      after graded SCI. MATERIALS AND METHODS: Anaesthetised rats were subjected to
      mild or severe cord contusion at T9. Estimation of SSAS patency was carried out
      at 1h and 1, 3, 7, 15, 30 and 90 days postinjury, as well as in naive rats, by
      quantifying the passage of superparamagnetic beads injected into the CSF at the
      cisterna magna and recovered at spinal level L2. CSF volume recovery was measured
      simultaneously. Data were analysed by the two-way ANOVA test. RESULTS: Estimation
      of SSAS patency revealed nearly complete blockage early after contusion that was
      unevenly restored entering the chronic stages. Volume of CSF recovered was also
      significantly decreased early after injury compared to naive rats, but was fully
      restored by 1 month postinjury. Overall, although modestly different from each
      other, changes in both parameters were more pronounced after severe rather than
      mild injuries for each time point examined. CONCLUSIONS: SCI alters SSAS patency.
      Its extent is a function primarily of time elapsed after lesion and secondly of
      injury severity. It is reasonable to expect that disturbances in SASS patency
      might alter CSF dynamics and impair self-reparative mechanisms and intrathecal
      therapeutics, making SSAS patency blockage a key target for SCI management.

PMID- 25616677
TI  - Impact of intraoperative hypotension and blood pressure fluctuations on early
      postoperative delirium after non-cardiac surgery.
AB  - INTRODUCTION: Postoperative delirium is common in older patients. Despite its
      prognostic significance, the pathophysiology is incompletely understood. Although
      many risk factors have been identified, no reversible factors, particularly ones
      potentially modifiable by anaesthetic management, have been identified. The goal
      of this prospective cohort study was to investigate whether intraoperative
      hypotension was associated with postoperative delirium in older patients
      undergoing major non-cardiac surgery. METHODS: Study subjects were patients >65
      years of age, undergoing major non-cardiac surgery, who were enrolled in an
      ongoing prospective observational study of the pathophysiology of postoperative
      delirium. Intraoperative blood pressure was measured and predefined criteria were
      used to define hypotension. Delirium was measured by the Confusion Assessment
      Method on the first two postoperative days. Data were analysed using t-tests, two
      sample proportion tests and ordered logistic regression multivariable models,
      including correction for multiple comparisons. RESULTS: Data from 594 patients
      with a mean age of 73.6 years (sd 6.2) were studied. Of these 178 (30%) developed
      delirium on day 1 and 176 (30%) on day 2. Patients developing delirium were
      older, more often female, had lower preoperative cognitive scores, and underwent
      longer operations. Relative hypotension (decreases by 20, 30, or 40%) or absolute
      hypotension [mean arterial pressure (MAP)<50 mm Hg] were not significantly
      associated with postoperative delirium, nor was the duration of hypotension
      (MAP<50 mm Hg). Conversely, intraoperative blood pressure variance was
      significantly associated with postoperative delirium. DISCUSSION: These results
      showed that increased blood pressure fluctuation, not absolute or relative
      hypotension, was predictive of postoperative delirium.

PMID- 25616678
TI  - Domain structure of growth signalobodies critically affects the outcome of
      antibody library selection.
AB  - Wide applications of antibodies have demanded rapid and easy methods for
      isolating high-affinity antibodies. We recently developed an antibody screening
      system in mammalian cells using a growth signalobody, which is a single-chain Fv
      (scFv) library/cytokine receptor chimera that can transduce a growth signal in
      response to a target oligomeric antigen. However, we have never investigated how
      the domain structure of signalobodies affects the outcome of library screening.
      In this study, we screened naive scFv library-inserted signalobodies having
      distinct extracellular and transmembrane (TM) domains. Although the previously
      constructed signalobody with the extracellular D1/D2 domains of erythropoietin
      receptor had recovered the clones with high affinity against a target antigen and
      with low background cell growth, its D1/D2-deficient variant which was tested in
      this study recovered the clones with low affinity against a target antigen and
      with considerable background cell growth. In addition, mutagenesis in the TM
      domain lowered the level of the background cell growth. These results suggest
      that the D1/D2 domains increase a threshold to activate signalobodies, thereby
      selecting clones with high affinity against a target antigen and that the TM
      domain could be engineered to minimize background growth signalling. 

PMID- 25616679
TI  - Hyperuricemia Is an Independent Predictor of Contrast-Induced Acute Kidney Injury
      and Mortality in Patients Undergoing Percutaneous Coronary Intervention.
AB  - We investigated whether hyperuricemia is an independent predictor of contrast
      induced acute kidney injury (CI-AKI) and mortality in patients undergoing
      percutaneous coronary intervention (PCI). In a single-center study of 1772
      patients undergoing PCI, the development of CI-AKI and mortality during a 2.8
      year median follow-up period was assessed. The incidence of CI-AKI was
      significantly higher in the hyperuricemic group than in the normouricemic group
      (5.78% vs 1.76%, P < .001). According to multivariate analysis (after adjusting
      for potential confounding factors), hyperuricemia predicted CI-AKI (odds ratio:
      1.962; 95% confidence interval [CI]: 1.014-3.798; P = .045). The other risk
      factors for CI-AKI were >75 years, emergent PCI, chronic kidney disease (CKD),
      and anemia. Hyperuricemia with a tendency toward significantly independently
      predicted long-term mortality, after adjusting for CI-AKI, CKD, and emergent PCI
      (hazard ratio: 1.571; 95% CI: 1.006-2.452; P = .047). In patients undergoing PCI,
      hyperuricemia is associated with a risk of CI-AKI. Furthermore, after adjusting
      for other variables, including CI-AKI and CKD, long-term mortality after PCI was
      higher in those with hyperuricemia than with normouricemia. 

PMID- 25616680
TI  - Comparison of Risk Scores for Prediction of Complications following Aortic Valve
      Replacement.
AB  - BACKGROUND: Risk models play an important role in stratification of patients for
      cardiac surgery, but their prognostic utilities for post-operative complications
      are rarely studied. We compared the EuroSCORE, EuroSCORE II, Society of Thoracic
      Surgeon's (STS) Score and an Australasian model (Aus-AVR Score) for predicting
      morbidities after aortic valve replacement (AVR), and also evaluated seven STS
      complications models in this context. METHODS: We retrospectively calculated risk
      scores for 620 consecutive patients undergoing isolated AVR at Auckland City
      Hospital during 2005-2012, assessing their discrimination and calibration for
      post-operative complications. RESULTS: Amongst mortality scores, the EuroSCORE
      was the best at discriminating stroke (c-statistic 0.845); the EuroSCORE II at
      deep sternal wound infection (c=0.748); and the STS Score at composite morbidity
      or mortality (c=0.666), renal failure (c=0.634), ventilation>24 hours (c=0.732),
      return to theatre (c=0.577) and prolonged hospital stay >14 days post-operatively
      (c=0.707). The individual STS complications models had a marginally higher c
      statistic (c=0.634-0.846) for all complications except mediastinitis, and had
      good calibration (Hosmer-Lemeshow test P-value 0.123-0.915) for all
      complications. CONCLUSION: The STS Score was best overall at discriminating post
      operative complications and their composite for AVR. All STS complications models
      except for deep sternal wound infection had good discrimination and calibration
      for post-operative complications.

PMID- 25616681
TI  - Intra-aortic balloon counterpulsation in contemporary practice - where are we?
AB  - The intra-aortic balloon pump (IABP) remains the most widely used form of
      mechanical circulatory support in current clinical practice. This article will
      review the current evidence to guide IABP use, focussing on large registry and
      prospective, randomised data, and seek to establish appropriate roles for the
      IABP in contemporary practice. Despite a paucity of clinical evidence, the IABP
      remains a useful clinical tool in selected settings, although its routine, up
      front use in relatively unselected MI populations is not supported by data.
      Although current evidence no longer supports routine use in certain high-risk
      groups, further studies of appropriately selected high-risk patients may yet
      demonstrate benefit in patients with moderate-severe degrees of shock. 

PMID- 25616683
TI  - Contributions to the morphology and phylogeny of the newly discovered bat tick
      species, Ixodes ariadnae in comparison with I. vespertilionis and I. simplex.
AB  - BACKGROUND: Recently a new hard tick species, Ixodes ariadnae has been
      discovered, adding to the two known ixodid tick species (I. vespertilionis and I.
      simplex) of bats in Europe. FINDINGS: Scanning electron microscopic comparison of
      adult females of these species shows morphological differences concerning the
      palps, the scutum, the Haller's organ, the coxae, as well as the arrangement and
      fine structure of setae. Molecular analysis of 10 geographically different
      isolates revealed 90-95% sequence homology in the 12S and 16S rDNA genes of bat
      tick species. Based on 12S rDNA sequences, genotypes of I. ariadnae clustered
      closest to I. simplex, whereas according to their 16S rDNA gene they were closest
      to I. vespertilionis. The subolesin gene of I. ariadnae had only 91% sequence
      homology with that of I. ricinus, and is the longest known among hard tick
      species. CONCLUSIONS: The present study illustrates the morphology and clarifies
      the phylogenetic relationships of the three known bat tick species that occur in
      Europe. According to its subolesin gene I. ariadnae may have a long evolutionary
      history.

PMID- 25616684
TI  - A multi-journal partnership to highlight joint first-authors of manuscripts.

PMID- 25616685
TI  - The Great Whoosh: Connecting an Online Personal Health Narrative and
      Communication Privacy Management.
AB  - This research study examined Bud Goodall's online health narrative as a case
      study through the use of a thematic analysis to investigate the presence of
      communication privacy management (CPM) theory. Emergent themes of humor as a
      privacy management strategy, legitimization of co-owners, shifting privacy rules
      at end of life, and metaphors as privacy protection were used to recount
      Goodall's cancer experience on his personal blog, connecting to the components of
      CPM. The themes the authors analyzed represent the push-pull dialectical tension
      experienced to reveal and conceal information, conceptualization of private
      information, shared boundaries, and boundary linkages. 

PMID- 25616686
TI  - Classification of 2-pore domain potassium channels based on rectification under
      quasi-physiological ionic conditions.
AB  - It is generally expected that 2-pore domain K(+) (K2P) channels are open or
      outward rectifiers in asymmetric physiological K(+) gradients, following the
      Goldman-Hodgkin-Katz (GHK) current equation. Although cloned K2P channels have
      been extensively studied, their current-voltage (I-V) relationships are not
      precisely characterized and previous definitions are contradictory. Here we study
      all the functional channels from 6 mammalian K2P subfamilies in transfected
      Chinese hamster ovary cells with patch-clamp technique, and examine whether their
      I-V relationships are described by the GHK current equation. K2P channels display
      2 distinct types of I-V curves in asymmetric physiological K(+) gradients. Two
      K2P isoforms in the TWIK subfamily conduct large inward K(+) currents and have a
      nearly linear I-V curve. Ten isoforms from 5 other K2P subfamilies conduct small
      inward K(+) currents and exhibit open rectification, but fits with the GHK
      current equation cannot precisely reveal the differences in rectification among
      K2P channels. The Rectification Index, a ratio of limiting I-V slopes for outward
      and inward currents, is used to quantitatively describe open rectification of
      each K2P isoform, which is previously qualitatively defined as strong or weak
      open rectification. These results systematically and precisely classify K2P
      channels and suggest that TWIK K(+) channels have a unique feature in regulating
      cellular function. 

PMID- 25616688
TI  - Dynamic excitation states and firing patterns are controlled by sodium channel
      kinetics in myenteric neurons: a simulation study.
AB  - Enteric neurons located in the gastro-intestinal tract are of particular
      importance to control digestive functions such as motility and secretion. In our
      recent publication, we showed that mouse myenteric neurons exhibit 2 types of
      tetrodotoxin-resistant Na(+) currents: a fast inactivating Na(+) current produced
      by Nav1.5 channels, present in nearly all myenteric neurons, and a persistent
      Na(+) current attributed to Nav1.9 channels, restricted to the intrinsic primary
      afferent neurons (IPANs). By combination of experimental recording and computer
      simulation we found that Nav1.5 contributed to the upstroke velocity of action
      potentials (APs), whereas Nav1.9 opposed AP repolarization. Here, we detailed the
      Na(+), Ca(2+) and K(+) currents used in our computational model of IPAN. We
      refined the prototype cell to reproduce the sustained firing pattern recorded in
      situ. As shown in experimental conditions we demonstrated that Nav1.9 channels
      critically determine the up-state life-time and thus, are essential to sustain
      tonic firing. 

PMID- 25616687
TI  - Organization of cGMP sensing structures on the rod photoreceptor outer segment
      plasma membrane.
AB  - A diffusion barrier segregates the plasma membrane of the rod photoreceptor outer
      segment into 2 domains; one which is optimized for the conductance of ions in the
      phototransduction cascade and another for disk membrane synthesis. We propose the
      former to be named "phototransductive plasma membrane domain," and the latter to
      be named "disk morphogenic plasma membrane domain." Within the phototransductive
      plasma membrane, cGMP-gated channels are concentrated in striated membrane
      features, which are proximally located to the sites of active cGMP production
      within the disk membranes. For proper localization of cGMP-gated channel to the
      phototransductive plasma membrane, the glutamic acid-rich protein domain encoded
      in the beta subunit plays a critical role. Quantitative study suggests that the
      disk morphogenic domain likely plays an important role in enriching rhodopsin
      prior to its sequestration into closed disk membranes. Thus, this and our
      previous studies provide new insight into the mechanism that spatially organizes
      the vertebrate phototransduction cascade. 

PMID- 25616690
TI  - A meta-study of qualitative research examining determinants of children's
      independent active free play.
AB  - PURPOSE: To produce a meta-study by completing a systematic review of qualitative
      research examining determinants of independent active free play in children.
      METHOD: Following systematic electronic and manual searches and application of
      inclusion/exclusion criteria, 46 studies were retained and subjected to meta
      method, meta-theory, and meta-data analyses, followed by a final meta-synthesis.
      RESULTS: Identified determinants of independent active free play were child
      characteristics (age, competence, and gender), parental restrictions (safety
      concerns and surveillance), neighborhood and physical environment (fewer children
      to play with, differences in preferences for play spaces between parents and
      children, accessibility and proximity, and maintenance), societal changes
      (reduced sense of community, good parenting ideal, changing roles of parents,
      privatization of playtime and play spaces), and policy issues (need to give
      children voice). An ecological model depicting these factors, and the
      relationships therein, was created. CONCLUSIONS: This comprehensive meta-study
      helps establish a knowledge base for children's independent active free play
      research by synthesizing a previously fragmented set of studies. Parents'
      perceived safety concerns are the primary barrier to children's active free play.
      These safety concerns are moderated by child-level factors (age, competence,
      gender) and broader social issues. Interventions should focus on community-level
      solutions that include children's perspectives. From a methods perspective, the
      reviewed studies used a range of data collection techniques, but methodological
      details were often inadequately reported. The theoretical sophistication of
      research in this area could be improved. To this end, the synthesis reported in
      this study provides a framework for guiding future research.

PMID- 25616691
TI  - Incidence and predictors of cardiac catheterisation-related arterial thrombosis
      in children.
AB  - OBJECTIVE: Arterial thrombosis is one of the most reported complications of
      cardiac catheterisation (CC) in children. The aim of the study was to evaluate
      the incidence and predictors of arterial thrombosis in children with cardiac
      diseases (CDs). METHODS: During 12 consecutive months, all children aged 0-19
      years undergoing CC of the femoral arteries were included in this observational
      study. After CC, clinical evaluation of impaired limb perfusion was performed
      according to local guidelines. Doppler ultrasonography was performed when
      decreased limb perfusion was suspected. RESULTS: 123 children (30% aged <12
      months, 70% aged >12 months) underwent CC. Arterial thrombosis occurred in 14 of
      the 123 children (11.4%). Twelve cases (12/14=86%) of arterial thrombosis
      occurred in infants aged <12 months and 2 (2/14=14%) in older children. Overall
      younger age (p<0.01, OR (95% CI) 0.49 (0.28 to 0.86)) and low body weight
      (p<0.004, OR (95% CI) 0.78 (0.65 to 0.92)) were significantly associated with an
      increased risk of arterial thrombosis. Cyanotic CD (p=0.07, OR (95% CI) 2.87
      (0.90 to 9.15)) showed a trend towards increased thrombotic risk. CONCLUSIONS:
      Arterial thrombosis is a common complication of CC in infants. Diagnosis of CC
      related arterial thrombosis remains a challenge. Well-defined clinical monitoring
      protocols may be valuable methods for timely detection and treatment of arterial
      thrombosis.

PMID- 25616693
TI  - Reply: The 'cognitions' index of the Parkinson's disease questionnaire-39 relates
      to sleep disturbances and hallucinations.

PMID- 25616692
TI  - Evaluation of palpation, pressure algometry, and electromyography for monitoring
      trigger points in young participants.
AB  - OBJECTIVE: The aims of this study were to assess trigger points (TrPs), their
      pain threshold, and the activity of motor units in the neck and shoulder girdle
      muscles of young volunteers and to assess palpation, algometry, and surface
      electromyography (EMG) for their detection. METHODS: Seventy participants aged
      from 19 to 26 years (20.6 +/- 1.4 years [mean +/- SD]) were examined to identify
      TrPs through palpation, an algometer test for pressure pain threshold (PPT), a
      test for the activity of muscle motor units at rest (rEMG) and at maximal
      contraction (mcEMG) with surface EMG recordings. RESULTS: Palpation studies
      revealed numerous symmetrical nonreferring latent TrPs (379/560 performed tests),
      referring latent TrPs (91/560), and few active TrPs (4/560). Algometry confirmed
      the lowest PPT in active TrPs and the highest PPT in participants with no TrPs
      (86/560). Pressure pain thresholds were lower in nonpregnant women than in men,
      especially in the trapezius and sternocleidomastoid muscles with nonreferring and
      referring latent TrPs. Trigger points evoked a moderate increase of rEMG
      amplitude but with no evident changes in mcEMG. CONCLUSIONS: This study showed
      that the preliminary algometry and rEMG recordings monitored a decrease in PPT
      and an increase in muscle tension in all cases of TrPs in each of the 3 types
      detected in people younger than 30 years.

PMID- 25616694
TI  - The burden of non-motor symptoms in Parkinson's disease using a self-completed
      non-motor questionnaire: a simple grading system.
AB  - BACKGROUND: Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually
      every patient, yet they are under-recognized and under-treated. The NMS
      Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful
      for NMS screening in clinic. OBJECTIVE: Development of a straight forward grading
      classification of the burden of non-motor symptoms in PD based on the number of
      NMS as assessed by the NMS Questionnaire. METHODS: In an observational, cross
      sectional, international study of 383 consecutive patients distribution of the
      declared NMS as per NMSQuest was analyzed according to previously published
      levels based on the Non-Motor Symptoms Scale and also the median and
      interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores.
      After post hoc checking, these values were proposed as cut-off points for
      estimating NMS burden based only on the accumulation of symptoms. RESULTS: Burden
      and number of NMS correlate closely (r >= 0.80). On the basis of this finding,
      five levels (0 = No NMS to 4 = Very severe) of NMSQuest grading were proposed
      after identification of their cut-offs by ordinal logistic regression and median
      and interquartile range distribution. These values coincided almost completely
      with those obtained by median and interquartile range in an independent sample.
      Concordance between this classification and HY staging was weak (weighted kappa =
      0.30), but was substantial (weighted kappa = 0.68) with the Non-Motor Symptoms
      Scale grading. CONCLUSION: Completion of NMSQuest and subsequent grading of the
      burden could allow the health care professional to approach the severity of NMS
      burden using the self completed NMSQuest in a primary care setting.

PMID- 25616695
TI  - BCL2 is an independent predictor of outcome in basal-like triple-negative breast
      cancers treated with adjuvant anthracycline-based chemotherapy.
AB  - Neither targeted therapies nor predictors for chemotherapy sensitivity are
      available for triple-negative breast cancer (TNBC). Our study included 187
      patients with TNBC, 164 of whom were treated with anthracycline-based adjuvant
      chemotherapy. Eleven molecular biomarkers were analyzed. BCL2, epidermal growth
      factor receptor (EGFR), MYC, TOP2A, and Ki-67 protein expression was evaluated by
      immunohistochemistry. The status of the EGFR, MYC, and TOP2A genes and
      chromosomes 7, 8, and 17 was assessed using fluorescence in situ hybridization.
      High BCL2 expression predicted poor relapse-free survival (RFS) in patients
      treated with anthracycline-based adjuvant chemotherapy (p = 0.035), poor breast
      cancer-specific survival (BCSS) (p = 0.048), and a trend to poor overall survival
      (OS) (p = 0.085). High levels of BCL2 expression predicted poor OS in basal-like
      (BL) TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p
      = 0.033, hazard ratio (HR) 3.04, 95 % confidence interval (CI) 1.04-8.91) and a
      trend to poor RFS (log-rank p = 0.079) and poor BCSS (log-rank p = 0.056).
      Multivariate analysis showed that BCL2 status, tumor size, and nodal status all
      had independent predictive significance for RFS (p = 0.005, p = 0.091, p = 0.003,
      respectively; likelihood ratio test for the whole model, p = 0.003), BCSS (p =
      0.012, p = 0.077, p = 0.01, respectively; likelihood ratio test for the whole
      model, p = 0.016), and OS (p = 0.008, p = 0.004, p = 0.004, respectively;
      likelihood ratio test for the whole model, p = 0.0006). Similarly, multivariate
      analysis for BL TNBC showed BCL2, tumor size, and nodal status all had
      independent predictive significance for RFS (likelihood ratio test for the whole
      model, p = 0.00125), BCSS (p = 0.00035), and OS (p = 0.00063). High EGFR
      expression was associated with poor BCSS (p = 0.039) in patients treated with
      anthracycline-based adjuvant chemotherapy. Patients who underwent anthracycline
      based adjuvant chemotherapy and exhibited CMYC amplification had a trend to worse
      BCSS (p = 0.066). In conclusion, high BCL2 expression is a significant
      independent predictor of poor outcome in TNBC patients treated with anthracycline
      based adjuvant chemotherapy, and this is the first study showing the BCL2
      prediction in BL TNBC. BCL2 expression analysis could facilitate decision making
      on adjuvant treatment in TNBC patients.

PMID- 25616696
TI  - XRCC1 polymorphisms associated with survival among Chinese bladder cancer
      patients receiving epirubicin and mitomycin C.
AB  - The association between DNA repair gene polymorphisms and bladder cancer risk has
      been widely studied. However, only few studies have examined the correlation
      between bladder cancer and instillation agent sensitivity. The aim of this study
      was to examine the association between polymorphisms of DNA repair genes, namely
      X-ray repair cross-complementing group I (XRCC1) rs2854509 and rs3213255, and
      bladder cancer recurrence risk. We recruited 244 patients (130 treated with
      epirubicin and 114 treated with mitomycin C). Genomic DNA was used to examine the
      XRCC1 rs2854509 and rs3213255 genotypes by Taqman PCR analysis. Combination
      analysis of XRCC1 rs2854509 and rs3213255 and examination of XRCC1 diplotypes
      were performed to reveal possible correlations. The rs2854509 CC and rs3213255 TT
      genotypes conferred shorter survival times than the rs2854509 AC/AA and rs3213255
      CC/CT genotypes in patients treated with epirubicin, but not in those treated
      with mitomycin C (MMC) in adjusted models [hazard ratio (HR) = 0.23, 95 %
      confidence interval (CI) = 0.10-0.53 for rs2854509 AC + AA compared with CC; HR =
      0.17, 95 % CI = 0.06-0.46 for rs3213255 CC + CT compared with TT]. Combination
      analysis showed significantly increased recurrence-free survival (RFS) among
      patients simultaneously carrying the rs2854509 AC/AA and rs3213255 CC/CT
      genotypes with an HR of 0.15 (95 % CI = 0.05-0.45) compared to those carrying
      other genotypes. Diplotype analysis demonstrated that the A-C/C-T diplotype is
      associated with a lower risk of recurrence compared with the common wild C-T/C-T
      diplotype (HR = 0.17, 95 % CI = 0.06-0.51). Our results suggest that the
      rs2854509 CC and rs3213255 TT genotypes confer higher sensitivity to epirubicin
      instillation. Moreover, the A-C/C-T diplotype presents significantly lower
      recurrence risk than other diplotypes.

PMID- 25616697
TI  - Role of vitamin D receptor gene polymorphisms in pancreatic cancer: a case
      control study in China.
AB  - The study was conducted to investigate the relationship between vitamin D
      receptor (VDR) gene rs2228570 and rs1544410 polymorphisms and pancreatic cancer
      (PC). Two hundred fifty-eight PC patients and 385 healthy controls were enrolled
      in this study. The genotypes of rs2228570 and rs1544410 were assayed using the
      polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP)
      method. Univariate and multivariate logistic regression analyses were applied to
      determine the association between PC-onset risk and VDR gene polymorphisms.
      Contingency table analysis was performed to evaluate the relationship between the
      gene polymorphisms and clinicopathological tumor features such as location,
      pathological differentiation, and the TNM classification of PC. In rs2228570, the
      T loci and genotypes with T allele could increase the risk of PC; in rs1544410,
      the G loci and genotypes AG + GG could decrease the onset risk of PC
      significantly. The contingency table analysis indicated that the rs2228570
      polymorphisms were correlated with the pathological differentiation of PC
      significantly, and the rs1544410 polymorphisms were correlated with the TNM
      classification of PC significantly. In conclusion, the VDR gene polymorphisms
      were correlated with incidence, pathological differentiation, and the TNM
      classification of PC significantly in our study population. So, the VDR
      polymorphisms have important implications in the incident rate and survival rate
      of PC.

PMID- 25616698
TI  - Surgical treatment of ipsilateral multi-level femoral fractures.
AB  - BACKGROUND: Concurrent ipsilateral fractures of the proximal and shaft of the
      femur are rare complex fracture combinations. In this prospective cohort study,
      we evaluated clinical and radiological long-term results after operative
      treatment using several surgical strategies: the so-called "rendezvous" surgical
      technique, e.g., the combination of retrograde intramedullary nailing and dynamic
      hip screw (DHS) osteosynthesis, or the all-in-one device technique, e.g., long
      cephalomedullary nail, compared with two non-overlapping implants (e.g.,
      conventional technique). METHODS: In a 10-year-period from 2004 to 2013, we
      treated 65 patients with complex ipsilateral multi-level femoral fractures.
      Median age was 45 years (range 19-90 years). Fractures were classified according
      to the AO/OTA classification. Four patients died during intensive care unit
      treatment due to multi-organ failure prior to definitive osteosynthesis. Clinical
      long-term outcome using the functional system of Friedman/Wyman as well as
      radiological outcome was evaluated 2 years after trauma (range 13-42 months).
      RESULTS: All-in-one device was used in 36 patients, "rendezvous" technique in 9
      patients, and the conventional technique in the remaining 16 patients. Two years
      after trauma, complete fracture healing was found in 57 out of 61 patients
      ("rendezvous": 9, all-in-one device: 33, conventional: 15; p-value: 0.66). There
      was no significant difference regarding the complication rate in the cohort
      groups ("rendezvous": 3, all-in-one device: 13, conventional: 5; p-value: 0.94).
      Using the functional assessment system of Friedman/Wyman 2 years after trauma, a
      good clinical result was found in 77.7% in the "rendezvous" group, in 77.8% in
      the all-in-one device group, and in 75% in the conventional group. CONCLUSION:
      The indication for operative stabilization of ipsilateral multi-level femoral
      fractures is considered an urgent and emergency procedure. Based on the
      successful long-term results of this study, we prefer the "rendezvous" technique
      with fracture stabilization from distally to proximally. Both fracture components
      require stable fixation. It is advisable to stabilize the shaft fracture
      primarily using external fixation (damage control orthopedics) and the proximal
      femoral fracture using early definitive internal fixation. In a second and staged
      operation, the external fixator is removed and the shaft fracture is stabilized
      using retrograde nail osteosynthesis with overlapping of the DHS and nail
      implants.

PMID- 25616699
TI  - Postnatal ovarian development and its relationship with steroid hormone receptors
      in JiNing Grey goats.
AB  - In this work, we examined the ovarian development and its relationship with
      steroid hormone receptors levels and the precocious puberty in JiNing Gray goats
      by using optical microscopy, immunohistochemistry, quantitative real-time RT-PCR
      (qPCR) and Western blotting. We found that in the ovaries of neonatal kids, high
      level of receptors for estrogen (ERalpha and ERbeta) and progesterone (PR) and
      their mRNA were observed along with growing follicles. From 0 to 30 days of age,
      the weight and volume of ovaries increased significantly and the boundary between
      the inner and outer cortex disappeared, while the expression of ERalpha, ERbeta
      and PR and their mRNA decreased sharply. When 60 days old, the animals began to
      ovulate; the expression of ERalpha, ERbeta and PR and their mRNA significantly
      increased, and the animals reached puberty. On day 90, the animals manifested
      sexual maturity with biggest mature follicles 6.18mm in diameter, the expression
      of ERbeta and PR protein and their mRNA was maintained at a high level, with
      decreased expression of ERalpha and its mRNA. Before puberty, the expression of
      ovarian ERalpha (prepubertal dominant receptor) and it's mRNA was significantly
      higher than that of ERbeta (dominant receptor after sexual maturity). The results
      showed that JiNing Grey goats' ovaries had fast development and early maturation,
      and ERalpha, ERbeta and PR protein and mRNA expression in the ovary had distinct
      specificity for time and space, which may be closely related to the strain's
      progenitive characteristics. 

PMID- 25616701
TI  - Review of plasmonic fiber optic biochemical sensors: improving the limit of
      detection.
AB  - This paper presents a brief overview of the technologies used to implement
      surface plasmon resonance (SPR) effects into fiber-optic sensors for chemical and
      biochemical applications and a survey of results reported over the last ten
      years. The performance indicators that are relevant for such systems, such as
      refractometric sensitivity, operating wavelength, and figure of merit (FOM), are
      discussed and listed in table form. A list of experimental results with reported
      limits of detection (LOD) for proteins, toxins, viruses, DNA, bacteria, glucose,
      and various chemicals is also provided for the same time period. Configurations
      discussed include fiber-optic analogues of the Kretschmann-Raether prism SPR
      platforms, made from geometry-modified multimode and single-mode optical fibers
      (unclad, side-polished, tapered, and U-shaped), long period fiber gratings
      (LPFG), tilted fiber Bragg gratings (TFBG), and specialty fibers (plastic or
      polymer, microstructured, and photonic crystal fibers). Configurations involving
      the excitation of surface plasmon polaritons (SPP) on continuous thin metal
      layers as well as those involving localized SPR (LSPR) phenomena in nanoparticle
      metal coatings of gold, silver, and other metals at visible and near-infrared
      wavelengths are described and compared quantitatively. 

PMID- 25616700
TI  - Structural and functional changes in glaucoma: comparing the two-flash multifocal
      electroretinogram to optical coherence tomography and visual fields.
AB  - PURPOSE: To correlate multifocal electroretinogram (mfERG) findings in the
      macular area of glaucoma patients with automated perimetry (visual fields) and
      with optical coherence tomography (OCT). METHODS: A two-global flash mfERG
      (VERISTM) was recorded in 20 eyes with primary open-angle glaucoma. The root mean
      square was calculated, and three response epochs were analysed: the direct
      component (15-45 ms) and two induced components (IC-1 at 45-75 ms and IC-2 at 75
      105 ms). The central 10 degrees  of the mfERG was compared to the central 10
      degrees  of the OCT and of the visual field. Responses grouped in a superior and
      in an inferior semicircle, extending between 10 degrees  and 20 degrees , were
      also compared to the corresponding areas of the OCT and of the visual fields. In
      addition, the area of the papillomacular bundle was also analysed separately.
      RESULTS: In glaucoma patients, mfERG responses showed a significant positive
      association with retinal thickness in the central 10 degrees  for IC2 (p = 0.001)
      and a trend for IC1 (p = 0.066). A significant association was found between the
      central IC1 and IC2 of the mfERG and corresponding perimetric sensitivities
      expressed in linear units (p < 0.01). The OCT showed a positive association with
      visual field sensitivities (p < 0.05) in all areas examined (p < 0.05).
      Separation of the papillomacular bundle area did not improve structure-function
      association further. CONCLUSIONS: In our study, mfERG showed a statistically
      significant correlation with perimetric sensitivity measured in linear units and
      with structural macular changes detected with time-domain OCT.

PMID- 25616702
TI  - Novel calibration tools and validation concepts for microarray-based platforms
      used in molecular diagnostics and food safety control.
AB  - Commercial platforms consisting of ready-to-use microarrays printed with target
      specific DNA probes, a microarray scanner, and software for data analysis are
      available for different applications in medical diagnostics and food analysis,
      detecting, e.g., viral and bacteriological DNA sequences. The transfer of these
      tools from basic research to routine analysis, their broad acceptance in
      regulated areas, and their use in medical practice requires suitable calibration
      tools for regular control of instrument performance in addition to internal assay
      controls. Here, we present the development of a novel assay-adapted calibration
      slide for a commercialized DNA-based assay platform, consisting of precisely
      arranged fluorescent areas of various intensities obtained by incorporating
      different concentrations of a "green" dye and a "red" dye in a polymer matrix.
      These dyes present "Cy3" and "Cy5" analogues with improved photostability, chosen
      based upon their spectroscopic properties closely matching those of common labels
      for the green and red channel of microarray scanners. This simple tool allows to
      efficiently and regularly assess and control the performance of the microarray
      scanner provided with the biochip platform and to compare different scanners. It
      will be eventually used as fluorescence intensity scale for referencing of assays
      results and to enhance the overall comparability of diagnostic tests. 

PMID- 25616703
TI  - Application of a 1,1,3,3-tetramethylguanidine (TMG)/MeOH-CO2 in situ
      derivatization procedure for the gas chromatographic characterization of the
      fatty acid profile in olive oil.
AB  - 1,1,3,3-Tetramethylguanidine (TMG), methanol and carbon dioxide were investigated
      as switchable polarity solvents (SPS) in the simultaneous derivatization and
      extraction of triacylglycerols for the gas chromatographic (GC) characterization
      of olive oil. Three commercial olive oils were used as test samples. Results of
      the developed method did not differ statistically from those provided by
      reference derivatization procedures. The transesterification reaction was carried
      out under a very mild condition, one step and in situ, and no particular matrix
      interferences were evidenced. The method represented the first example of the use
      of a switchable polarity mixture for the preparation of methyl ester derivatives
      of fatty acids (FAME). 

PMID- 25616704
TI  - A genetic variant regulating miR-126 is associated with sight threatening
      diabetic retinopathy.
AB  - BACKGROUND: The regulation of miR-126 by rs4636297 single nucleotide polymorphism
      (SNP) has been implicated in the pathogenesis of neovascularisation by promoting
      vascular endothelial growth factor, suggesting it could be associated with sight
      threatening diabetic retinopathy (STDR), but has not been previously investigated
      or reported. MATERIALS AND METHODS: A case control study of 531 individuals with
      diabetes was genotyped for the rs4636297 SNP, using the Sequenom iPLEX Gold
      chemistry. STDR included people with severe non-proliferative diabetic
      retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Association was
      tested using logistic regression analysis, adjusting for confounding variables.
      RESULTS: In an additive model, the A allele of rs4636297 SNP is significantly
      associated with STDR compared to people with none or mild diabetic retinopathy
      (DR) (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 1.22-3.35, p =
      0.006). CONCLUSION: The A allele of rs4636297, known to be the non-functional
      allele for post-translational regulation of miR-126, is associated with STDR.
      This finding suggests that this locus would be a potential therapeutic target for
      inhibiting the development of DR.

PMID- 25616705
TI  - The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and
      early signs of atherosclerosis in childhood diabetes.
AB  - BACKGROUND: Advanced protein glycation is an important mechanism for the
      development of late diabetic complications including atherosclerosis.
      Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation
      end product in human plasma. AIM: To investigate the relationship between
      methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in
      children and adolescents with type 1 diabetes and healthy controls. METHODS: A
      total of 314 diabetes patients aged 8-18 years were compared with 120 healthy
      controls. Serum methylglyoxal-derived hydroimidazolone-1 was measured by
      immunoassay. Atherosclerosis was evaluated by assessing carotid intima-media
      thickness by ultrasound, arterial stiffness by Young's modulus and inflammation
      by C-reactive protein. RESULTS: Methylglyoxal-derived hydroimidazolone-1 was
      significantly increased in the diabetes group compared with controls, 155.3
      (standard deviation (SD) = 41.0) versus 143.0 (SD = 35.1) U/mL, p = 0.003, as was
      C-reactive protein, median 0.51 (0.27, 1.83) versus 0.31 (0.19, 0.67) mg/L, p <
      0.001. There was no significant difference between the groups regarding carotid
      intima-media thickness or Young's modulus. Multiple regression analysis showed a
      significant positive association between methylglyoxal-derived hydroimidazolone-1
      and C-reactive protein in the diabetes group. CONCLUSION: Serum levels of
      methylglyoxal-derived hydroimidazolone-1 in diabetes patients are increased and
      associated with low-grade inflammation, but not yet arterial stiffness or wall
      thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be
      important in the early phase of the accelerated atherosclerotic process in
      diabetes.

PMID- 25616706
TI  - Prevalence of type 2 diabetes is higher in peripheral artery disease than in
      coronary artery disease patients.
AB  - Type 2 diabetes mellitus and pre-diabetes are risk factors for atherosclerosis
      and are highly prevalent in patients with coronary artery disease. However, the
      prevalence of impaired glucose metabolism in patients with peripheral artery
      disease is not as well elucidated. We aimed at comparing prevalence rates of type
      2 diabetes mellitus and pre-diabetes, which were diagnosed according to the
      current American Diabetes Association criteria, among 364 patients with
      peripheral artery disease, 529 patients with coronary artery disease and 383
      controls. The prevalence of type 2 diabetes mellitus in peripheral artery disease
      patients was 49.7%. It was significantly higher in these patients than in
      coronary artery disease patients (34.4%; p < 0.001) and controls (21.4%; p <
      0.001). Adjusted for sex, age and body mass index, odds ratios for type 2
      diabetes mellitus were 2.0 (95% confidence interval 1.5-2.6) comparing the
      peripheral artery disease group with the coronary artery disease group (p <
      0.001) and 4.0 (2.8-5.8) comparing the peripheral artery disease group with
      controls (p < 0.001). The prevalence of pre-diabetes among non-diabetic subjects
      was high in all three study groups (64.5% in peripheral artery disease patients,
      63.4% in coronary artery disease patients and 61.8% in controls), without
      significant between-group differences. In conclusion, the prevalence of type 2
      diabetes mellitus is even higher in peripheral artery disease patients than in
      coronary artery disease patients. This observation underlines the need to
      consider impaired glucose regulation in the management of peripheral artery
      disease.

PMID- 25616707
TI  - Probing SGLT2 as a therapeutic target for diabetes: basic physiology and
      consequences.
AB  - Traditional treatments for type 1 and type 2 diabetes are often associated with
      side effects, including weight gain and hypoglycaemia that may offset the
      benefits of blood glucose lowering. The kidneys filter and reabsorb large amounts
      of glucose, and urine is almost free of glucose in normoglycaemia. The sodium
      dependent glucose transporter (SGLT)-2 in the early proximal tubule reabsorbs the
      majority of filtered glucose. Remaining glucose is reabsorbed by SGLT1 in the
      late proximal tubule. Diabetes enhances renal glucose reabsorption by increasing
      the tubular glucose load and the expression of SGLT2 (as shown in mice), which
      maintains hyperglycaemia. Inhibitors of SGLT2 enhance urinary glucose excretion
      and thereby lower blood glucose levels in type 1 and type 2 diabetes. The load
      dependent increase in SGLT1-mediated glucose reabsorption explains why SGLT2
      inhibitors in normoglycaemic conditions enhance urinary glucose excretion to only
      ~50% of the filtered glucose. The role of SGLT1 in both renal and intestinal
      glucose reabsorption provides a rationale for the development of dual SGLT1/2
      inhibitors. SGLT2 inhibitors lower blood glucose levels independent of insulin
      and induce pleiotropic actions that may be relevant in the context of lowering
      cardiovascular risk. Ongoing long-term clinical studies will determine whether
      SGLT2 inhibitors have a safety profile and exert cardiovascular benefits that are
      superior to traditional agents. 

PMID- 25616708
TI  - Educational interventions in peritoneal dialysis: a narrative review of the
      literature.
AB  - OBJECTIVES: To review the current literature on educational interventions used in
      peritoneal dialysis (PD). Educational interventions have become increasingly
      relevant because they play a key role in helping individuals to actively
      participate in their therapy and to manage their chronic condition. The paper
      will focus on two areas: (a) educational interventions for individuals living
      with PD and (b) educational interventions for PD nurses. DESIGN: A narrative
      review of primary research. DATA SOURCES: Electronic searches of the MEDLINE,
      CINAHL, EMBASE, ERIC and Cochrane Library (2006-2013) databases were undertaken
      using terms such as peritoneal dialysis, insertive training, curriculum, nursing
      education, train the trainer, coach the coach, tutor the tutor, and patient
      education were used. All studies were reviewed by two researchers. REVIEW
      METHODS: Titles and abstracts of 555 studies were screened and read. Full text
      articles retrieved were further screened against the inclusion and exclusion
      criteria. Relevant data on the educational interventions for people receiving PD
      and nurse training programs were extracted and synthesized narratively. RESULTS:
      Eighteen articles met the inclusion criteria. Most of them focused on educational
      intervention programs for people undergoing PD. Findings on the link between the
      PD trainer's background and peritonitis rates among individuals undergoing PD are
      inconsistent. PD learners should be taught self-management skills as well as
      technical skills. They might also benefit from receiving decision-making aids.
      Older people, people with co-morbidities and people with low educational status
      need more time to acquire self-care skills and are more likely to develop
      peritonitis. Home visits have the potential to improve learning outcomes. Re
      training needs should be assessed and fulfilled as appropriate. Case and disease
      management programs have been shown to have positive outcomes for individuals
      receiving PD. CONCLUSIONS: Educational interventions for PD remain an under
      researched area, despite the potential they have to make this type of therapy
      more successful. Further research on education and training for people receiving
      PD and for PD nurses is needed. In the meantime, educational interventions used
      for other chronic conditions could provide guidance.

PMID- 25616709
TI  - Systematic Review and Meta-analysis of Factors Determining Change to Radical
      Treatment in Active Surveillance for Localized Prostate Cancer.
AB  - CONTEXT: Many men with clinically localized prostate cancer are being monitored
      as part of active surveillance (AS) programs, but little is known about reasons
      for receiving radical treatment. OBJECTIVES: A systematic review of the evidence
      about AS was undertaken, with a meta-analysis to identify predictors of radical
      treatment. EVIDENCE ACQUISITION: A comprehensive search of the Embase, MEDLINE
      and Web of Knowledge databases to March 2014 was performed. Studies reporting on
      men with localized prostate cancer followed by AS or monitoring were included. AS
      was defined where objective eligibility criteria, management strategies, and
      triggers for clinical review or radical treatment were reported. EVIDENCE
      SYNTHESIS: The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr
      (range of medians 1.5-7.5 yr). The cohorts had a wide range of inclusion
      criteria, monitoring protocols, and triggers for radical treatment. There were
      eight prostate cancer deaths and five cases of metastases in 24,981 person-years
      of follow-up. Each year, 8.8% of men (95% confidence interval 6.7-11.0%) received
      radical treatment, most commonly because of biopsy findings, prostate-specific
      antigen triggers, or patient choice driven by anxiety. Studies in which most men
      changed treatment were those including only low-risk Gleason score 6 disease and
      scheduled rebiopsies. CONCLUSIONS: The wide variety of AS protocols and lack of
      robust evidence make firm conclusions difficult. Currently, patients and
      clinicians have to make judgments about the balance of risks and benefits in AS
      protocols. The publication of robust evidence from randomized trials and longer
      term follow-up of cohorts is urgently required. PATIENT SUMMARY: We reviewed 26
      studies of men on active surveillance for prostate cancer. There was evidence
      that studies including men with the lowest risk disease and scheduled rebiopsy
      had higher rates of radical treatment.

PMID- 25616710
TI  - EAU guidelines on renal cell carcinoma: 2014 update.
AB  - CONTEXT: The European Association of Urology Guideline Panel for Renal Cell
      Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for
      RCC management. OBJECTIVES: To provide an update of the 2010 RCC guideline based
      on a standardised methodology that is robust, transparent, reproducible, and
      reliable. EVIDENCE ACQUISITION: For the 2014 update, the panel prioritised the
      following topics: percutaneous biopsy of renal masses, treatment of localised RCC
      (including surgical and nonsurgical management), lymph node dissection,
      management of venous thrombus, systemic therapy, and local treatment of
      metastases, for which evidence synthesis was undertaken based on systematic
      reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta
      analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library,
      trial registries, conference proceedings) were searched (January 2000 to November
      2013) including randomised controlled trials (RCTs) and retrospective or
      controlled studies with a comparator arm. Risk of bias (RoB) assessment and
      qualitative and quantitative synthesis of the evidence were performed. The
      remaining sections of the document were updated following a structured literature
      assessment. EVIDENCE SYNTHESIS: All chapters of the RCC guideline were updated.
      For the various systematic reviews, the search identified a total of 10,862
      articles. A total of 151 studies reporting on 78,792 patients were eligible for
      inclusion; where applicable, data from RCTs were included and meta-analyses were
      performed. For RCTs, there was low RoB across studies; however, clinical and
      methodological heterogeneity prevented data pooling for most studies. The
      majority of studies included were retrospective with matched or unmatched cohorts
      based on single or multi-institutional data or national registries. The exception
      was for systemic treatment of metastatic RCC, in which several RCTs have been
      performed, resulting in recommendations based on higher levels of evidence.
      CONCLUSIONS: The 2014 guideline has been updated by a multidisciplinary panel
      using the highest methodological standards, and provides the best and most
      reliable contemporary evidence base for RCC management. PATIENT SUMMARY: The
      European Association of Urology Guideline Panel for Renal Cell Carcinoma has
      thoroughly evaluated available research data on kidney cancer to establish
      international standards for the care of kidney cancer patients.

PMID- 25616711
TI  - Evaluation of the effects of LLLT on biomechanical properties of tibial diaphysis
      in two rat models of experimental osteoporosis by a three point bending test.
AB  - Osteoporosis (OP) is a disease which causes bone loss and fractures, leading to
      severe pain and deformity. This study has aimed to assess the effects of pulsed
      wave low-level laser therapy (PW LLLT) on cortical bone in two experimental
      models of OP in rats. There were four ovariectomized (OVX-d) groups and four
      dexamethasone-treated groups. The healthy group were considered for baseline
      evaluations. At 14 weeks following ovariectomy, the OVX-d rats were further
      subdivided into the following: control rats with OP, OVX-d rats that received
      alendronate (1 mg/kg), OVX-d rats treated with LLLT, and OVX-d rats treated with
      alendronate and LLLT. The remaining rats received dexamethasone for 5 weeks and
      were divided into four groups: control, alendronate-treated rats (1 mg/kg), laser
      treated rats, and laser-treated rats with concomitant administration of
      alendronate. The rats received alendronate for 30 days. LLLT (890 nm, 80 Hz,
      0.972 J/cm(2)) was performed on the tibias three times per week for 8 weeks.
      After 8 weeks, tibias were extracted and submitted to a three-point bending test.
      PW LLLT did not increase the biomechanical parameters of osteoporotic bones
      compared to controls and healthy rats. PW LLLT associated with alendronate
      treatment significantly increased stress high load in OVX-d rats compared to the
      healthy group. PW LLLT at the current study parameters failed to cause beneficial
      biomechanical effects in the examined osteoporotic cortical bones. PW LLLT
      associated with alendronate treatment produced a more remarkable effect on bone
      strength in the ovariectomized induced OP rat model. 

PMID- 25616712
TI  - Monitoring morphological alterations during invasive ductal breast carcinoma
      progression using multiphoton microscopy.
AB  - Morphological alteration of cells and matrices is critical for tumor initiation
      and progression. Monitoring these alterations during tumor progression is vitally
      important for making real-time histological diagnoses of tumor staging. In this
      study, 20 pairs of normal and cancerous human breast tissues were imaged by
      multiphoton microscopy (MPM), and nuclear area and collagen density were
      quantified by LSM 5 software (version 3.2). Comparison of MPM images from normal
      breast tissue with low- and high-grade invasive ductal carcinoma (IDC) lesions
      clearly showed changes in both cellular features and extracellular matrix
      architecture during IDC development. Moreover, analysis of nuclear area and
      collagen density established a quantitative link between these two morphological
      features and progression of IDC. Present results demonstrated that MPM can
      provide both qualitative and quantitative evaluations of tumor progression. With
      additional development, this technique has the potential to make real-time
      histological diagnoses of tumor staging and guide development of efficacious
      clinical therapies. 

PMID- 25616714
TI  - Role of Rhipicephalus microplus cheliceral receptors in gustation and host
      differentiation.
AB  - Rhipicephalus microplus is considered the most economically important
      ectoparasite of cattle worldwide. It is known that zebuine breeds of cattle are
      less susceptible to tick infestation than taurine breeds. Contact chemoreceptors
      in the cheliceral pit sensilla of ticks respond selectively to phagostimulant
      compounds, however their role in blood feeding relative to host susceptibility to
      infestation remains to be fully understood. We addressed this topic by conducting
      taste electrophysiology experiments with cheliceral pit sensilla preparations of
      R. microplus females. Solutions of five known ixodid tick phagostimulants were
      tested at different concentrations: sodium (NaCl), and potassium chloride (KCl)
      (10(-3)-10(-1)M); glucose (10(-4)-10(-1)M); adenosine triphosphate (ATP) (10(-6)
      10(-2)M); and reduced l-glutathione (GSH) (10(-6)-10(-2)M). Serum samples from
      six susceptible animals of the Girolando breed (5/8 Bos indicus*3/8 B. taurus)
      and six resistant Nelore bovines (pure B. indicus) were also tested. A dose
      dependent response of gustatory neurons associated with the chelicerae sensillum
      to NaCl, glucose, GSH, and ATP were observed. Responses by the cheliceral inner
      digit pit sensilla of R. microplus to KCl and glucose were also observed and they
      are reported here for the first time. In addition to an electrophysiological
      response to known phagostimulants, chemoreceptors in the chelicera of R.
      microplus responded differently to serum from cattle susceptible and resistant to
      infestation. The cheliceral pit neurons were more responsive to serum of R.
      microplus resistant bovines with a higher mean spike frequency (53.5+/-2spikess(
      1)) than to serum samples from susceptible cattle (40.3+/-2spikess(-1)). The
      implications of chemosensation during tick blood feeding are discussed. 

PMID- 25616713
TI  - Low-level laser irradiation modulates cell viability and creatine kinase activity
      in C2C12 muscle cells during the differentiation process.
AB  - Low-level laser irradiation (LLLI) is increasingly used to treat musculoskeletal
      disorders, with satisfactory results described in the literature. Skeletal muscle
      satellite cells play a key role in muscle regeneration. The aim of the present
      study was to evaluate the effect of LLLI on cell viability, creatine kinase (CK)
      activity, and the expression of myogenic regulatory factors in C2C12 myoblasts
      during the differentiation process. C2C12 cells were cultured in Dulbecco's
      modified Eagle's medium (DMEM) containing 2% horse serum and submitted to
      irradiation with GaAlAs diode laser (wavelength, 780 nm; output power, 10 mW;
      energy density, 5 J/cm2). Cell viability and the expression of myogenic
      regulatory factors were assessed 24, 48, and 72 h after irradiation by 3-(4,5
      dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT) assay and
      quantitative real-time polymerase chain reaction (RT-qPCR), respectively. CK
      activity was analyzed at 24 and 72 h. An increase in cell viability was found in
      the laser group in comparison to the control group at all evaluation times. CK
      activity was significantly increased in the laser group at 72 h. Myogenin
      messenger RNA (mRNA) demonstrated a tendency toward an increase in the laser
      group, but the difference in comparison to the control group was non-significant.
      In conclusion, LLLI was able to modulate cell viability and CK activity in C2C12
      myoblasts during the differentiation process.

PMID- 25616716
TI  - Versatile functions for IL-6 in metabolism and cancer.
AB  - Owing to its abundance in inflammatory settings, interleukin IL-6 is frequently
      viewed as a proinflammatory cytokine, with functions that parallel those of tumor
      necrosis factor (TNF) and IL-1beta in the context of inflammation. However,
      accumulating evidence points to a broader role for IL-6 in a variety of
      (patho)physiological conditions, including functions related to the resolution of
      inflammation. We review recent findings on the complex biological functions
      governed by IL-6 signaling, focusing on its role in inflammation-associated
      cancer and metabolic disorders such as obesity and type 2 diabetes mellitus
      (T2DM). We propose that the anti-inflammatory functions of IL-6 may extend to
      multiple settings and cell types, and suggest that these dimensions should be
      incorporated in therapeutic approaches to these diseases. Finally, we outline
      important areas of inquiry towards understanding this pleiotropic cytokine. 

PMID- 25616715
TI  - Revisiting the role of B cells in skin immune surveillance.
AB  - Whereas our understanding of the skin immune system has increased exponentially
      in recent years, the role of B cells in cutaneous immunity remains poorly
      defined. Recent studies have revealed the presence of B cells within lymphocytic
      infiltrates in chronic inflammatory skin diseases and cutaneous malignancies
      including melanoma, and have examined their functional significance in these
      settings. We review these findings and discuss them in the context of the current
      understanding of the role of B cells in normal skin physiology, as well as in
      both animal and human models of skin pathology. We integrate these findings into
      a model of cutaneous immunity wherein crosstalk between B cells and other skin
      resident immune cells plays a central role in skin immune homeostasis. 

PMID- 25616717
TI  - A prospective cohort study of depression in pregnancy, prevalence and risk
      factors in a multi-ethnic population.
AB  - BACKGROUND: Depression in pregnancy increases the risk of complications for
      mother and child. Few studies are done in ethnic minorities. We wanted to
      identify the prevalence of depression in pregnancy and associations with
      ethnicity and other risk factors. METHOD: Population-based, prospective cohort of
      749 pregnant women (59% ethnic minorities) attending primary antenatal care
      during early pregnancy in Oslo between 2008 and 2010. Questionnaires covering
      demographics, health problems and psychosocial factors were collected through
      interviews. Depression in pregnancy was defined as a sum score >= 10 by the
      Edinburgh Postnatal Depression Scale (EPDS) at gestational week 28. RESULTS: The
      crude prevalence of depression was; Western Europeans: 8.6% (95% CI: 5.45-11.75),
      Middle Easterners: 19.5% (12.19-26.81), South Asians: 17.5% (12.08-22.92), and
      other groups: 11.3% (6.09-16.51). Median EPDS score was 6 in Middle Easterners
      and 3 in all other groups. Middle Easterners (OR = 2.81; 95% CI (1.29-6.15)) and
      South Asians (2.72 (1.35-5.48)) had significantly higher risk for depression than
      other minorities and Western Europeans in logistic regression models. When
      adjusting for socioeconomic position and family structure, the ORs were reduced
      by 16-18% (OR = 2.44 (1.07-5.57) and 2.25 (1.07-4.72). Other significant risk
      factors were the number of recent adverse life events, self-reported history of
      depression and poor subjective health three months before conception. CONCLUSION:
      The prevalence of depression in pregnancy was higher in ethnic minorities from
      the Middle East and South Asia. The increased risk persisted after adjustment for
      risk factors.

PMID- 25616718
TI  - Recruiting for values in healthcare: a preliminary review of the evidence.
AB  - Displaying compassion, benevolence and respect, and preserving the dignity of
      patients are important for any healthcare professional to ensure the provision of
      high quality care and patient outcomes. This paper presents a structured search
      and thematic review of the research evidence relating to values-based recruitment
      within healthcare. Several different databases, journals and government reports
      were searched to retrieve studies relating to values-based recruitment published
      between 1998 and 2013, both in healthcare settings and other occupational
      contexts. There is limited published research related to values-based recruitment
      directly, so the available theoretical context of values is explored alongside an
      analysis of the impact of value congruence. The implications for the design of
      selection methods to measure values is explored beyond the scope of the initial
      literature search. Research suggests some selection methods may be appropriate
      for values-based recruitment, such as situational judgment tests (SJTs),
      structured interviews and multiple-mini interviews (MMIs). Personality tests were
      also identified as having the potential to compliment other methods (e.g.
      structured interviews), as part of a values-based recruitment agenda. Methods
      including personal statements, references and unstructured/'traditional'
      interviews were identified as inappropriate for values-based recruitment.
      Practical implications are discussed in the context of values-based recruitment
      in the healthcare context. Theoretical implications of our findings imply that
      prosocial implicit trait policies, which could be measured by selection tools
      such as SJTs and MMIs, may be linked to individuals' values via the behaviours
      individuals consider to be effective in given situations. Further research is
      required to state this conclusively however, and methods for values-based
      recruitment represent an exciting and relatively unchartered territory for
      further research. 

PMID- 25616719
TI  - Thinking about the un-thinking.

PMID- 25616720
TI  - The role of environmental and individual characteristics in the development of
      student achievement: a comparison between a traditional and a problem-based
      learning curriculum.
AB  - In medical education, the effect of the educational environment on student
      achievement has primarily been investigated in comparisons between traditional
      and problem-based learning (PBL) curricula. As many of these studies have reached
      no clear conclusions on the superiority of the PBL approach, the effect of
      curricular reform on student performance remains an issue. We employed a
      theoretical framework that integrates antecedents of student achievement from
      various psychosocial domains to examine how students interact with their
      curricular environment. In a longitudinal study with N = 1,646 participants, we
      assessed students in a traditional and a PBL-centered curriculum. The measures
      administered included students' perception of the learning environment, self
      efficacy beliefs, positive study-related affect, social support, indicators of
      self-regulated learning, and academic achievement assessed through progress
      tests. We compared the relations between these characteristics in the two
      curricular environments. The results are two-fold. First, substantial relations
      of various psychosocial domains and their associations with achievement were
      identified. Second, our analyses indicated that there are no substantial
      differences between traditional and PBL-based curricula concerning the relational
      structure of psychosocial variables and achievement. Drawing definite conclusions
      on the role of curricular-level interventions in the development of student's
      academic achievement is constrained by the quasi-experimental design as wells as
      the selection of variables included. However, in the specific context described
      here, our results may still support the view of student activity as the key
      ingredient in the acquisition of achievement and performance. 

PMID- 25616721
TI  - Editorial: Siegfried Hoyer's concept of Alzheimer pathophysiology.
AB  - The concept of central insulin resistance and dysfunctional insulin signaling in
      Alzheimer's Disease (AD) has been developed by Siegfried Hoyer in 1985-2000. It
      is widely recognized that the mechanisms underlying neuronal energy deficiency
      and in particular to elucidate insulin/insulin receptor cascade deficiencies are
      some of the most relevant proximate characteristics of sporadic AD. The imbalance
      between cerebral oxygen utilization and cerebral glucose utilization may cause
      rise in reactive oxygen species production and this might be causal for synapse
      degeneration. This concept has been substantiated by work on postmortem Alzheimer
      brains and has been translated back into the streptozotozin animal model, which
      has stimulated much further research by other researchers. Finally, the insulin
      hypothesis of Alzheimer's disease has currently advanced into a potential
      therapeutic avenue. 

PMID- 25616722
TI  - Erratum to: Negative feedback of miR-29 family TET1 involves in hepatocellular
      cancer.
AB  - Primary hepatocellular carcinoma (HCC) is the most common form of liver cancer
      and is one of the most common malignancies worldwide. Tumor suppressor gene
      silencing through DNA methylation contributes to cancer formation. The ten-eleven
      translocations (TET) family of alpha-ketogluta-rate-dependent dioxygenases
      catalyzes the sequential oxidation of 5-methylcytosine to 5-hydroxymethyl
      cytosine, 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA
      demethylation. MicroRNAs are an abundant class of 17-25 nucleotides small
      noncoding RNAs, identified as important regulators of many diverse biological
      processes. In this study, we showed that TET1 expression was obviously reduced in
      the majority of examined HCC tissues. And we further investigated the expression
      and functional involvement of TET1 in proliferation, migration and invasion and
      determined that TET1 may function as a tumor suppressor. miR-29b was proved to
      inhibit metastasis through the targeting of TET1, indicating that downregulation
      of miR-29 may involve in HCC carcinogenesis and progression through potentiation
      of TET1 expression. Thus, we elucidated the roles of feedback of miR-29-TET1
      downregulation in HCC development and suggested a potential target in
      identification of the prognosis and application of cancer therapy for HCC
      patients. 

PMID- 25616724
TI  - Who provides GP after-hours care?
AB  - Understanding the demographic and financial factors likely to influence the
      supply side of after-hours GP care is crucial in meeting the increasing demand
      for these services. This study answers two questions: which GPs are more likely
      to provide after-hours GP care, and of those who do, which are more likely to
      take a heavier load. Data from the first wave of the Medicine in Australia:
      Balancing Employment and Life (MABEL) survey is used, with logistic regression
      applied to address the decision to undertake after-hours work and linear
      regression to address the question of the quantum of work. The results show that
      female, older, and urban GPs are less likely to work outside of normal hours. GPs
      who are employees are less likely to participate in after-hours work than GPs who
      are principals or partners of a practice. On the other hand, principals and
      partners, are likely work more hours in the after-hours period than employee GPs
      if they do participate in this work. Similarly, those GPs in solo practice who
      work after-hours also tend to take a heavier after-hours workload than the GPs
      who are not in solo practice. The role of GP wages and family income does not
      seem to be compelling. These conclusions are likely to relate to the ways doctors
      behave independent of the health system. 

PMID- 25616723
TI  - Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet
      chemotherapy for advanced non-small cell lung cancer patients with activating
      epidermal growth factor receptor mutations.
AB  - Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR
      TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC)
      in patients with activating EGFR mutations. However, there have been little
      evidence-based studies of gefitinib in combination with platinum-doublet therapy
      in these patients. We performed a phase II trial to determine the efficacy and
      safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first
      line treatment. This was a multicentre, single-arm, phase II trial of
      carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR
      mutations. Patients received four courses of these drugs in 3-4 week cycles. In
      each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80
      mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same
      regimen without carboplatin was administered until disease progression or
      unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was
      the primary endpoint, while response rate (RR), PFS, overall survival (OS), and
      safety were secondary endpoints. Thirty-five patients were enrolled into this
      study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for
      all patients was 17.6 months (95% confidence interval 15.5-infinity), but the
      median OS was not reached, because 28 patients were still alive after a median
      follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher)
      included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%),
      while non-haematological adverse events (grade 3 or higher) included elevated
      aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No
      interstitial lung disease or treatment-related deaths occurred. Combination
      chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well
      tolerated as a first-line treatment in advanced NSCLC patients with activating
      EGFR mutations.

PMID- 25616725
TI  - Depression and onset of cardiovascular disease in the US middle-aged and older
      adults.
AB  - OBJECTIVES: To examine the relationship between depression and onset of
      cardiovascular disease (CVD) among the US middle-aged and older adults. METHODS:
      The study sample came from 1992-2010 waves of the Health and Retirement Study, a
      nationally representative longitudinal survey, consisting of 8597 community
      dwelling adults aged 51-61 years old in 1992 with no CVD history. A score of >=3
      on the 8-item Center for Epidemiologic Studies Depression Scale was used to
      define clinically relevant depressive symptoms. Kaplan-Meier estimator and Cox
      proportional hazards model were performed to examine the association between
      baseline depressive symptoms and future CVD event. Subgroup analyses were
      conducted by sex and race/ethnicity. RESULTS: Compared with their counterparts
      without clinically relevant depressive symptoms, adults with clinically relevant
      depressive symptoms in 1992 were 27% (hazard ratio [HR] = 1.27, 95% confidence
      interval = 1.17-1.39) more likely to report new diagnosis of CVD during the 18
      years of follow-up. A significant dose-response relationship was present between
      severity of depressive symptoms and elevated CVD risk. The adjusted HRs for males
      and Hispanics appeared moderately larger than for their female and non-Hispanic
      white or African American counterparts, although the differences were not
      statistically significant. CONCLUSION: Holistic promotion of mental health
      through prevention, education, treatment, and rehabilitation is warranted to
      reduce CVD risk in the US middle-aged and older population.

PMID- 25616726
TI  - [3H]Ifenprodil binding in post-mortem brains of Cloninger type 1 and 2
      alcoholics: a whole-hemisphere autoradiography study.
AB  - The glutamate N-methyl-d-aspartate (NMDA) receptor NR2B subunits are sensitive to
      ethanol and are found in brain areas related to ethanol addiction, dependence,
      development of alcohol tolerance, and alcohol withdrawal syndrome. Previous
      studies indicate that early-onset Cloninger type 2 alcoholics have an intact,
      responsive, dopaminergic system in the nucleus accumbens (NAC), whereas type 1
      alcoholics have dopaminergic defects. NR2B-containing NMDA receptors in the NAC
      are involved in both non-opioid and opioid receptor-mediated reward. Our aim was
      to evaluate the putative [(3)H]ifenprodil binding alterations of NR2B receptors
      in limbic, hippocampal, and cortical brain areas of type 1 alcoholics (n=8), type
      2 alcoholics (n=8), and control subjects (n=10) by postmortem whole hemisphere
      autoradiography. We found significantly different binding levels among these
      three subject groups, and the main difference was localized in the decreased
      binding in type 2 alcoholics and controls in the nucleus accumbens. Although
      preliminary and from relatively small diagnostic groups, these results suggest
      pathological alterations in the NR2B-mediated reward system of type 2 alcoholics.

PMID- 25616727
TI  - Regulation of surface expression of TRPV2 channels in the retinal pigment
      epithelium.
AB  - PURPOSE: The retinal pigment epithelium (RPE) interacts closely with the
      photoreceptors in fulfilling tasks of visual function. Since an understanding of
      the RPE function is essential for understanding the patho-mechanisms involved in
      vision loss, we explored the regulation of the vanilloid receptor subtype
      transient receptor potential TRPV2 channels that trigger insulin-like growth
      factor-1 (IGF-1)-induced vascular endothelial growth factor A (VEGF-A) secretion.
      METHODS: Immunohistochemistry was used to assess TRPV2 expression in retinal
      cross-sections or ARPE-19 cells, and surface expression of TRPV2 was quantified
      using confocal microscopy. Membrane currents of ARPE-19 cells were recorded using
      a whole-cell configuration of the patch-clamp technique. RESULTS: TRPV2
      expression was detected in the RPE of the mouse retina as well as in ARPE-19
      cells. Increasing the temperature to 45  degrees C activated membrane conductance
      sensitive to SKF-96365 and ruthenium red in 60 % of cells. Preincubation with
      either cannabidiol (CBD) or IGF-1 led to a three- or fourfold increase in current
      density, respectively, in all cells, which was blocked by SKF-96365. In contrast
      to IGF-1, CBD stimulation of membrane conductance was further increased by heat.
      TRPV2 surface expression was increased by both IGF-1 and CBD, with the increase
      by CBD twice as large as that by IGF-1. The phosphatidylinositol 3-kinase (PI3K)
      inhibitor LY294002 abolished the effects on membrane conductance and surface
      expression. CONCLUSIONS: Both CBD and IGF-1 enhance TRPV2 channel activity by
      specific proportions of both channel activation and PI 3-kinase-dependent surface
      expression: IGF-1 predominantly increases ion channel activity, whereas CBD is
      more active in increasing TRPV2 surface expression. Thus, differential regulation
      of TRPV2 surface expression is an important mechanism for modulating the
      responsiveness of the RPE to growth factors.

PMID- 25616728
TI  - Comparison of visual and anatomical outcomes of half-fluence and half-dose
      photodynamic therapy in eyes with chronic central serous chorioretinopathy.
AB  - PURPOSE: To compare visual and anatomical outcomes of half-fluence (HF) and half
      dose (HD) photodynamic therapy (PDT) in chronic central serous chorioretinopathy
      (CSC). Particular focus was given to photoreceptor recovery rate following
      treatment. METHODS: Retrospective review of 52 chronic CSC patients who underwent
      HF- or HD-PDT (26 patients per group). Best-corrected visual acuity and spectral
      domain optical coherence tomography findings were compared between groups.
      RESULTS: Average follow-up for HF- and HD-PDT was 20.7 +/- 7.2 and 22.3 +/- 6.1
      months respectively. Both groups had significant visual acuity improvements, as
      well as central foveal and subfoveal choroidal thickness reductions. Measured
      parameters were not significantly different between groups at any time point
      examined. Complete photoreceptor recovery, defined as a continuous ellipsoid zone
      with a discernible interdigitation zone, was observed at 12 months in 19 (73 %)
      and 14 patients (54 %) in the HF- and HD-PDT groups respectively (p = 0.150).
      Overall photoreceptor recovery rate was not different between groups (p = 0.301,
      log-rank test). Delayed (>12 months) photoreceptor recovery was significantly
      associated with baseline external limiting membrane disruption (OR: 21.7, 95 %
      CI: 1.7-285.4, p = 0.019), disease duration (years, OR: 1.9, 95 % CI: 1.2-3.0, p
      = 0.005), and fovea-to-PDT spot center distance (100 MUm unit, OR: 0.74, 95 % CI
      0.56-0.97, p = 0.027). However, delayed photoreceptor recovery was not
      significantly associated with PDT modality. CONCLUSION: Both HF- and HD-PDT are
      effective in treating chronic CSC. No significant differences in visual or
      anatomical outcomes were observed.

PMID- 25616729
TI  - The ream and run: not for every patient, every surgeon or every problem.
AB  - PURPOSE: The purpose of this paper is to provide some essential and basic
      information concerning the ream and run technique for shoulder arthroplasty.
      METHODS: In a total shoulder arthroplasty, the humeral head prosthesis
      articulates with a polyethylene glenoid surface placed on the bone of the
      glenoid. Failure of the glenoid component is recognised as the principal cause of
      failure of total shoulder arthroplasty. By contrast, in the ream and run
      procedure, the humeral head prosthesis articulates directly with the glenoid,
      which has been conservatively reamed to provide a stabilising concavity and
      maximal glenohumeral contact area for load transfer. While no interpositional
      material is placed on the surface of the glenoid, animal studies have
      demonstrated that the reamed glenoid bone forms fibrocartilage, which is firmly
      fixed to the reamed bony surface. Glenohumeral motion is instituted on the day of
      surgery and continued daily after surgery to mold the regenerating glenoid
      fibrocartilage. When the healing process is complete - as indicated by a good and
      comfortable range of motion - exercises and activities are added progressively
      without concern for glenoid component failure.  RESULTS: The experience to date
      indicates that a technically well done ream and run procedure can restore high
      levels of comfort and function to carefully selected patients with
      osteoarthritis, capsulorrhaphy arthroplathy, and posttraumatic arthritis.
      CONCLUSIONS: Patients considering the ream and run procedure should understand
      that this technique avoids the risks and limitations associated with a
      polyethylene glenoid component, but that it requires strong motivation to follow
      through on a rehabilitation course that may require many months. The outcome of
      this procedure depends on the body's regeneration of a new surface for the
      glenoid and requires rigorous adherence to a daily exercise program. This paper
      explains in detail the principal factors in patient selection and the key
      technical elements of the procedure. Clinical examples and outcomes are
      demonstrated.

PMID- 25616730
TI  - Treatment of fracture sequelae of the proximal humerus: anatomical vs reverse
      shoulder prosthesis.
AB  - The treatment of complex humeral fractures or fracture-dislocations presents
      several challenges. Late complications such as malunion, avascular necrosis, or
      nonunion are frequent and often lead to articular incongruence. Patients can be
      severely handicapped, presenting with considerable pain, stiffness, and important
      functional impairment. Stiff shoulders with distorted proximal humerus, soft
      tissue damage, a scarred deltoid, and rotator cuff tears make shoulder
      arthroplasty a challenging procedure, often with unpredictable results and a high
      risk of complications. The overall results of patients with old trauma are
      inferior to the results currently obtained in patients with primary
      osteoarthritis or with recent 4-part fractures who are treated initially with
      humeral head replacement. In certain circumstances, with important distortion of
      the proximal humerus, poor bone quality, rotator cuff lesions, or muscle atrophy
      a reverse shoulder arthroplasty can be proposed in elderly patients instead of a
      non-constrained arthroplasty. 

PMID- 25616731
TI  - Heat index and adjusted temperature as surrogates for wet bulb globe temperature
      to screen for occupational heat stress.
AB  - Ambient temperature and relative humidity are readily ava-ilable and thus
      tempting metrics for heat stress assessment. Two methods of using air temperature
      and relative humidity to create an index are Heat Index and Adjusted Temperature.
      The purposes of this article are: (1) to examine how well Heat Index and Adjusted
      Temperature estimated the wet bulb globe temperature (WBGT) index, and (2) to
      suggest how Heat Index and Adjusted Temperature can be used to screen for heat
      stress level. Psychrometric relationships were used to estimate values of actual
      WBGT for conditions of air temperature, relative humidity, and radiant heat at an
      air speed of 0.5 m/s. A relationship between Heat Index [ degrees F] and WBGT [
      degrees C] was described by WBGT = -0.0034 HI(2) + 0.96 HI - 34. At lower Heat
      Index values, the equation estimated WBGTs that were +/- 2  degrees C-WBGT around
      the actual value, and to about +/- 0.5  degrees C-WBGT for Heat Index values >
      100  degrees F. A relationship between Adjusted Temperature [ degrees F] and WBGT
      [ degrees C] was described by WBGT = 0.45 Tadj - 16. The actual WBGT was between
      1  degrees C-WBGT below the estimated value and 1.4  degrees C-WBGT above. That
      is, there was a slight bias toward overestimating WBGT from Adjusted Temperature.
      Heat stress screening tables were constructed for metabolic rates of 180, 300,
      and 450 W. The screening decisions were divided into four categories: (1) < alert
      limit, (2) < exposure limit, (3) hourly time-weighted averages (TWAs) of work and
      recovery, and (4) a caution zone for an exposure > exposure limit at rest. The
      authors do not recommend using Heat Index or Adjusted Temperature instead of
      WBGT, but they may be used to screen for circumstances when a more detailed
      analysis using WBGT is appropriate. A particular weakness is accounting for
      radiant heat; and neither air speed nor clothing was considered.

PMID- 25616732
TI  - Chronic kidney disease and recurrent falls in nursing home residents: a
      retrospective cohort study.
AB  - This study examined whether chronic kidney disease (CKD) is associated with
      recurrent falls in older adults in nursing homes (NHs). We used data abstracted
      over a six month period from 510 NH residents with a history of falls. Thirty
      five percent of the NH residents had CKD. In adjusted analyses, the incidence of
      recurrent falls was similar in those with and without CKD [fall rate ratio (FRR)
      1.00, 95% confidence interval (CI) 0.97-1.02]. Orthostatic hypotension (FRR 1.52,
      95% CI 1.12-2.05), history of falls during the prior six month period (FRR 1.25,
      95% CI 1.05-1.49), cane or walker use (FRR 1.64, 95% CI 1.16-2.33), and
      ambulatory dysfunction (FRR 1.47, 95% CI 1.23-1.75) were independently associated
      with increased fall rate. CKD was not an important predictor of falls in this
      cohort of nursing home residents with prior falls. Instead, traditional fall risk
      factors were much more strongly associated with recurrent falls. 

PMID- 25616733
TI  - Media Coverage of Toxic Risks: A Content Analysis of Pediatric Environmental
      Health Information Available to New and Expecting Mothers.
AB  - Mass media play a central role in providing environmental health information to
      the public. Despite several decades of environmental and health communication
      research, the nature of environmental health information available to one of the
      most vulnerable populations--new and expecting mothers--has received limited
      attention. To address this gap, this study poses two questions: (1) How prevalent
      is information related to prenatal and pediatric environmental health (PPEH) in
      the media, and (2) how much coverage do the most concerning chemical threats to
      PPEH receive? A content analysis of 2,543 texts in popular media sources (i.e.,
      the Associated Press [AP], parenting magazines, and parenting websites) from
      September 2012 to February 2013 revealed that roughly three pieces of PPEH
      information were made available to mothers daily. Prior research has shown that
      media coverage of environmental health issues has decreased over the years;
      however, these results suggest that at-risk populations are likely to encounter
      this type of information in the media. Also, while certain chemicals received
      ample coverage (i.e., pesticides, cigarette smoke, mercury), other issues deemed
      concerning by federal agencies did not (i.e., lead, phthalates). This study also
      introduces a novel method for harvesting online content encountered incidentally.
      Implications of these findings for communication research and practice are
      discussed.

PMID- 25616734
TI  - The Arabidopsis MYB96 transcription factor plays a role in seed dormancy.
AB  - Seed dormancy facilitates to endure environmental disadvantages by confining
      embryonic growth until the seeds encounter favorable environmental conditions for
      germination. Abscisic acid (ABA) and gibberellic acid (GA) play a pivotal role in
      the determination of the seed dormancy state. ABA establishes seed dormancy,
      while GA triggers seed germination. Here, we demonstrate that MYB96 contributes
      to the fine-tuning of seed dormancy regulation through the coordination of ABA
      and GA metabolism. The MYB96-deficient myb96-1 seeds germinated earlier than wild
      type seeds, whereas delayed germination was observed in the activation-tagging
      myb96-1D seeds. The differences in germination rate disappeared after
      stratification or after-ripening. The MYB96 transcription factor positively
      regulates ABA biosynthesis genes 9-CIS-EPOXYCAROTENOID DIOXYGENASE 2 (NCED2),
      NCED5, NCED6, and NCED9, and also affects GA biosynthetic genes GA3ox1 and
      GA20ox1. Notably, MYB96 directly binds to the promoters of NCED2 and NCED6,
      primarily modulating ABA biosynthesis, which subsequently influences GA
      metabolism. In agreement with this, hyperdormancy of myb96-1D seeds was recovered
      by an ABA biosynthesis inhibitor fluridone, while hypodormancy of myb96-1 seeds
      was suppressed by a GA biosynthesis inhibitor paclobutrazol (PAC). Taken
      together, the metabolic balance of ABA and GA underlies MYB96 control of primary
      seed dormancy. 

PMID- 25616735
TI  - The activity of the artemisinic aldehyde Delta11(13) reductase promoter is
      important for artemisinin yield in different chemotypes of Artemisia annua L.
AB  - The artemisinic aldehyde double bond reductase (DBR2) plays an important role in
      the biosynthesis of the antimalarial artemisinin in Artemisia annua. Artemisinic
      aldehyde is reduced into dihydroartemisinic aldehyde by DBR2. Artemisinic
      aldehyde can also be oxidized by amorpha-4,11-diene 12-hydroxylase and/or
      aldehyde dehydrogenase 1 to artemisinic acid, a precursor of arteannuin B. In
      order to better understand the effects of DBR2 expression on the flow of
      artemisinic aldehyde into either artemisinin or arteannuin B, we determined the
      content of dihydroartemisinic aldehyde, artemisinin, artemisinic acid and
      arteannuin B content of A. annua varieties sorted into two chemotypes. The high
      artemisinin producers (HAPs), which includes the '2/39', 'Chongqing' and 'Anamed'
      varieties, produce more artemisinin than arteannuin B; the low artemisinin
      producers (LAPs), which include the 'Meise', 'Iran#8', 'Iran#14', 'Iran#24' and
      'Iran#47' varieties, produce more arteannuin B than artemisinin. Quantitative PCR
      showed that the relative expression of DBR2 was significantly higher in the HAP
      varieties. We cloned and sequenced the promoter of the DBR2 gene from varieties
      of both the LAP and the HAP groups. There were deletions/insertions in the region
      just upstream of the ATG start codon in the LAP varities, which might be the
      reason for the different promoter activities of the HAP and LAP varieties. The
      relevance of promoter variation, DBR2 expression levels and artemisinin
      biosynthesis capabilities are discussed and a selection method for HAP varieties
      with a DNA marker is suggested. Furthermore, putative cis-acting regulatory
      elements differ between the HAP and LAP varieties. 

PMID- 25616737
TI  - Profiles of paralytic shellfish toxins in bivalves of low and elevated toxicities
      following exposure to Gymnodinium catenatum blooms in Portuguese estuarine and
      coastal waters.
AB  - Profiles of paralytic shellfish toxins (PSTs) were examined in 405 composite
      samples of Mytilus spp., Cerastoderma edule, Donax trunculus and Spisula solida
      collected between 2007 and 2012 from natural production areas in two estuaries
      (Aveiro and Mondego), two coastal lagoons (Obidos and Formosa), and three open
      coastal areas (Aguda, Comporta and Culatra). Toxin concentrations were obtained
      from the biotoxin monitoring programme database. Episodes of PST toxicity in
      Portugal have been associated with Gymnodinium catenatum blooms. Toxin profiles
      for each species showed no trend over the surveyed years. In general, profiles
      differ only slightly among areas, except for Obidos. However, toxin profiles in
      bivalves varied between low and elevated toxicities, corresponding to below and
      above the PST regulatory limit, respectively. The ratio R1=(C1+2):B1, which were
      the main toxins produced by G. catenatum cells, decreased considerably between
      elevated and low toxicity cockles, indicating the elimination of C1+2 or
      conversion of compounds into B1. R2=[(dcSTX)+(dcGTX2+3)]:[(C1+2)+(B1)], which
      represents the ratio of minor to major toxins in G. catenatum cells, increased
      substantially in wedge clams (D. trunculus) of low toxicity and less markedly in
      cockles (C. edule) and mussels (Mytilus spp.). These differences are interpreted
      as the predominance of a biotransformation phase after exposure to the algal
      bloom. The toxin profile of surf clams (S. solida) was dominated by decarbamoyl
      compounds, reflecting intense biotransformation during exposure to blooms. The
      higher ratio R2 in low toxicity samples suggests that elimination of the produced
      decarbamoyl toxins was slower than biotransformation. 

PMID- 25616736
TI  - Identification and characterization of plant-specific NAC gene family in canola
      (Brassica napus L.) reveal novel members involved in cell death.
AB  - NAC transcription factors are plant-specific and play important roles in plant
      development processes, response to biotic and abiotic cues and hormone signaling.
      However, to date, little is known about the NAC genes in canola (or oilseed rape,
      Brassica napus L.). In this study, a total of 60 NAC genes were identified from
      canola through a systematical analysis and mining of expressed sequence tags.
      Among these, the cDNA sequences of 41 NAC genes were successfully cloned. The
      translated protein sequences of canola NAC genes with the NAC genes from
      representative species were phylogenetically clustered into three major groups
      and multiple subgroups. The transcriptional activities of these BnaNAC proteins
      were assayed in yeast. In addition, by quantitative real-time RT-PCR, we further
      observed that some of these BnaNACs were regulated by different hormone stimuli
      or abiotic stresses. Interestingly, we successfully identified two novel BnaNACs,
      BnaNAC19 and BnaNAC82, which could elicit hypersensitive response-like cell death
      when expressed in Nicotiana benthamiana leaves, which was mediated by
      accumulation of reactive oxygen species. Overall, our work has laid a solid
      foundation for further characterization of this important NAC gene family in
      canola. 

PMID- 25616738
TI  - PICSO: from myocardial salvage to tissue regeneration.
AB  - Despite advances in primary percutaneous interventions (PPCI), management of
      microvascular obstructions in reperfused myocardial tissue remains challenging
      and is a high-risk procedure. This has led to renewed interest in the coronary
      venous system as an alternative route of access to the myocardium. This article
      reviews historical data describing therapeutic options via cardiac veins as well
      as discussing the clinical potential and limitations of a catheter intervention:
      pressure controlled intermittent coronary sinus occlusion (PICSO). Collected
      experimental and clinical information suggest that PICSO also offers the
      potential for tissue regeneration beyond myocardial salvage. A meta-analysis of
      observer controlled pICSO application in animal studies showed a dose dependent
      reduction in infarct size of 29.3% (p < 0.001). Additionally, a 4-fold increase
      of hemeoxygenase-1 gene expression (p < 0.001) in the center of infarction and a
      2.5 fold increase of vascular endothelial growth factor (VEGF) (p < 0.002) in
      border zones suggest that molecular pathways are initiating structural
      maintenance. Early clinical evidence confirmed significant salvage and event free
      survival in patients with acute myocardial infarction and risk reduction for
      event free survival 5 years after the acute event (p < 0.0001). This experimental
      and clinical evidence was recently corroborated using modern PICSO technology in
      PPCI showing a significant reduction of infarct size, when compared to matched
      controls (p < 0.04). PICSO enhances redistribution of flow towards deprived
      zones, clearing microvascular obstruction and leading to myocardial protection.
      Beyond salvage, augmentation of molecular regenerative networks suggests a second
      mechanism of PICSO involving the activation of vascular cells in cardiac veins,
      thus enhancing structural integrity and recovery.

PMID- 25616739
TI  - Understanding gender norms, nutrition, and physical activity in adolescent girls:
      a scoping review.
AB  - Public health is currently focused on childhood obesity, and the associated
      behaviors of physical activity and nutrition. Canadian youth are insufficiently
      active and do not meet nutritional guidelines. This is of particular concern for
      adolescent girls, as they are less active than boys, become less active as they
      age, and engage in unhealthy weight control behaviors. The purpose of this review
      is to determine what is known from the existing literature about how gender norms
      are understood in relation to the health-related behaviors of PA and nutrition in
      young girls. This scoping review follows the framework of Arksey and O'Malley,
      involving defining a research question, study identification and selection,
      charting, interpretation, summarizing, and reporting. In total, 28 documents are
      reviewed, and characteristics are summarized quantitatively and qualitatively.
      Five major themes are identified: (1) Girls' relationships with PA are complex
      and require negotiating gender roles, (2) the literature focuses on dieting
      rather than nutrition, (3) appearance and perceptions influence behaviors, (4)
      "body" focused discourse is significant to girls' experiences, and (5) social
      influences, institutions, and environments are influential and may offer
      opportunity for future research and action. Gaps in the literature are identified
      and discussed. It is concluded that young girls' activity and nutrition is
      affected by gender norms and feminine ideals through complex negotiations,
      perceptions, body-centered discourse, and societal influences. 

PMID- 25616741
TI  - Simple finite element methods for approximating predator-prey dynamics in two
      dimensions using MATLAB.
AB  - We describe simple finite element schemes for approximating spatially extended
      predator-prey dynamics with the Holling type II functional response and logistic
      growth of the prey. The finite element schemes generalize 'Scheme 1' in the paper
      by Garvie (Bull Math Biol 69(3):931-956, 2007). We present user-friendly, open
      source MATLAB code for implementing the finite element methods on arbitrary
      shaped two-dimensional domains with Dirichlet, Neumann, Robin, mixed Robin
      Neumann, mixed Dirichlet-Neumann, and Periodic boundary conditions. Users can
      download, edit, and run the codes from http://www.uoguelph.ca/~mgarvie/ . In
      addition to discussing the well posedness of the model equations, the results of
      numerical experiments are presented and demonstrate the crucial role that habitat
      shape, initial data, and the boundary conditions play in determining the
      spatiotemporal dynamics of predator-prey interactions. As most previous works on
      this problem have focussed on square domains with standard boundary conditions,
      our paper makes a significant contribution to the area. 

PMID- 25616740
TI  - Urinary albumin excretion in healthy adults: a cross sectional study of 24-hour
      versus timed overnight samples and impact of GFR and other personal
      characteristics.
AB  - BACKGROUND: Urinary albumin can be measured in 24 h or spot samples. The 24 h
      urinary albumin excretion rate is considered the gold standard, but is cumbersome
      to collect. Instead, often an overnight sample is collected, and adjusted for
      dilution. Proxies for 24 h excretion rate have been studied in diabetics, but
      seldom in healthy individuals. Our aims were to compare 24 h and overnight
      albumin excretion, to assess the impact of personal characteristics, and to
      examine correlations between the 24 h excretion rate and proxies such as the
      albumin to creatinine ratio (ACR). METHODS: Separate 24 h and overnight urine
      samples were collected from 152 healthy kidney donors. Urinary creatinine,
      specific gravity, collection time, and sample volume determined. Differences
      between 24 h and overnight samples were examined, and the effects of age, sex,
      smoking, body mass, glomerular filtration rate, and urinary flow rate were
      assessed. RESULTS: The 24 h albumin excretion rate and ACR were both
      significantly higher than their overnight counterparts. Unadjusted albumin was
      unsurprisingly higher in the more concentrated overnight samples, while
      concentrations adjusted for specific gravity were similar. In multivariate
      analysis, the 24 h excretion rate and proxies were positively associated with
      glomerular filtration rate, as was ACR in overnight samples. There were positive
      associations between urinary albumin and body mass. CONCLUSIONS: Proxies for the
      24 h albumin excretion rate showed relatively high correlations with this gold
      standard, but differences due to sampling period, adjustment method, and personal
      characteristics were large enough to be worth considering in studies of albumin
      excretion in healthy individuals.

PMID- 25616742
TI  - Indications for anti-reflux surgery in Barrett's esophagus.

PMID- 25616743
TI  - Expression profile and down-regulation of argininosuccinate synthetase in
      hepatocellular carcinoma in a transgenic mouse model.
AB  - BACKGROUND: Argininosuccinate synthetase (ASS) participates in urea and nitric
      oxide production and is a rate-limiting enzyme in arginine biosynthesis.
      Regulation of ASS expression appears complex and dynamic. In addition to
      transcriptional regulation, a novel post-transcriptional regulation affecting
      nuclear precursor RNA stability has been reported. Moreover, many cancers,
      including hepatocellular carcinoma (HCC), have been found not to express ASS
      mRNA; therefore, they are auxotrophic for arginine. To study when and where ASS
      is expressed and whether post-transcriptional regulation is undermined in
      particular temporal and spatial expression and in pathological events such as
      HCC, we set up a transgenic mouse system with modified BAC (bacterial artificial
      chromosome) carrying the human ASS gene tagged with an EGFP reporter. RESULTS: We
      established and characterized the transgenic mouse models based on the use of two
      BAC-based EGFP reporter cassettes: a transcription reporter and a
      transcription/post-transcription coupled reporter. Using such a transgenic mouse
      system, EGFP fluorescence pattern in E14.5 embryo was examined. Profiles of
      fluorescence and that of Ass RNA in in situ hybridization were found to be in
      good agreement in general, yet our system has the advantages of sensitivity and
      direct fluorescence visualization. By comparing expression patterns between mice
      carrying the transcription reporter and those carrying the transcription/post
      transcription couple reporter, a post-transcriptional up-regulation of ASS was
      found around the ventricular zone/subventricular zone of E14.5 embryonic brain.
      In the EGFP fluorescence pattern and mRNA level in adult tissues, tissue-specific
      regulation was found to be mainly controlled at transcriptional initiation.
      Furthermore, strong EGFP expression was found in brain regions of olfactory bulb,
      septum, habenular nucleus and choroid plexus of the young transgenic mice. On the
      other hand, in crossing to hepatitis B virus X protein (HBx)-transgenic mice, the
      Tg (ASS-EGFP, HBx) double transgenic mice developed HCC in which ASS expression
      was down-regulated, as in clinical samples. CONCLUSIONS: The BAC transgenic mouse
      model described is a valuable tool for studying ASS gene expression. Moreover,
      this mouse model is a close reproduction of clinical behavior of ASS in HCC and
      is useful in testing arginine-depleting agents and for studies of the role of ASS
      in tumorigenesis.

PMID- 25616744
TI  - The role of immunohistochemistry in the evaluation of gynecologic pathology: a
      single institutional experience.
AB  - Although morphology is the cornerstone of diagnostic pathology, it may be
      necessary to apply ancillary techniques, including immunohistochemistry (IHC) to
      resolve diagnostic problems. To provide some insights into IHC use in gynecologic
      (gyn) surgical pathology, we reviewed our institutional experience in using IHC
      during a 1-year period. A total number of 487 markers were ordered on 203 cases
      (2.4 markers/case). These 203 represented 4.8% of the 4216 gyn cases that were
      accessioned during the study period. Immunohistochemistry was used in 22 (9.3%)
      of 236 vulvar, 13 (9.2%) of 142 vaginal, 92 (5.9%) of 1557 cervical, 59 (3.5%) of
      1698 uterine, 1 (0.3%) of 311 fallopian tube, and 16 (6.9%) of 232 ovarian
      specimens. The most common markers were p16 (n = 125), Ki-67 (n = 69), and p53 (n
      = 59). Immunohistochemistry proved to be a valuable tool in separating benign
      from dysplastic or malignant categories, or to increase diagnostic certainty in
      the latter category, in 131 (65%) of the 203 cases where IHC was requested, and
      3.1% of all 4216 gyn cases examined. In the other 72 cases, IHC was utilized to
      histotype carcinomas, to define a site of origin for an established malignancy,
      or to assess the expression of predictive markers. Among 6 pathologists, years of
      practice and time spent on gyn service significantly affected IHC use, with less
      use with more than 10 years of practice and more than 10 weeks/year of service.
      This study documents IHC use at a tertiary care academic center and contributes
      data to define benchmarks for expected IHC use. 

PMID- 25616745
TI  - [Interventional procedures in the treatment of gastroesophageal reflux disease].
AB  - For patients with gastroesophageal reflux disease (GERD) who suffer from severe
      symptoms despite adequate medical therapy, interventional procedures are the only
      option for improving symptoms and thus the quality of life. In the clinical
      practice it is decisive if a hiatal hernia (HH) is present or not and whether it
      is larger or smaller than 2-3 cm. Patients who have a HH > 2-3 cm should undergo
      laparoscopic fundoplication with hiatal hernia repair. Patients with a larger HH
      are no longer eligible for endoscopic therapy as closure of the HH is not
      endoscopically possible. With the new laparoscopic methods (e.g. LINX and
      electrical stimulation) HH closure is theoretically possible but sufficient data
      is lacking. Furthermore, if a hiatal closure is additionally carried out the
      actual advantages of these methods are partly lost. Currently, outside of
      clinical trials only laparoscopic fundoplication can be recommended for patients
      with GERD and HH, because convincing long-term data are only available for this
      method. It seems that in clinical practice it is not so important what type of
      fundoplication is performed, more important seems to be the experience of the
      surgeon with the technique.

PMID- 25616746
TI  - [Perioperative CRP quantification for appendectomy: Clinically useful or a waste
      of money?].
AB  - BACKGROUND: Appendectomy is the most frequently performed non-elective surgical
      procedure in general surgery. Despite the questionable benefit, inflammatory
      markers, such as leukocyte count and C-related protein (CRP) are often determined
      before and after the surgical procedure. Clinicians are not infrequently
      confronted with the question whether a patient can be discharged despite an
      increase in inflammatory laboratory parameters. OBJECTIVES: The aim of the
      current study was to retrospectively evaluate the clinical course of patients
      after appendectomy and the correlation with inflammatory laboratory findings.
      MATERIAL AND METHODS: A total of 969 patients underwent a surgical procedure due
      to clinically suspected acute appendicitis. All clinical, laboratory and
      histopathological data were obtained from the patient records and a quality
      control database. Laboratory results were correlated with clinical and
      histopathological data (e.g. t-test, chi (2)-test, regression analysis and ROC
      curves). RESULTS: In patients without acute appendicitis operative trauma caused
      an increase in CRP up to a median of 31 mg/dl on the first postoperative day and
      up to 47 mg/dl on postoperative day 2. The overall morbidity was 6.2%. The
      strongest predictive parameter for complications was a CRP of more than 108 mg/l
      on the first postoperative day with an odds ratio of 16.6 (96% CI 6.4/42.8, p <
      0.001, specificity 88% and sensitivity 69%). Patients with CRP values below the
      threshold suffered from complications in 1.1 % of cases in contrast to patients
      above the threshold in 16.8% of cases (p < 0.001). CONCLUSION: A moderate
      postoperative elevation of CRP values is not a general contraindication for
      discharge; however, postoperative determination of CRP serum values after
      appendectomy might be an effective predictor for complications and should
      therefore be measured in the clinical routine.

PMID- 25616748
TI  - Estimation of carbon dioxide sequestration potential of microalgae grown in a
      batch photobioreactor.
AB  - The carbon dioxide (CO2) sequestration potential of two microalgae, Chlorella
      pyrenoidosa and Scenedesmus abundans was evaluated in a tubular batch
      photobioreactor with provision for continuous flow of 10% CO2 enriched air
      through the headspace. CO2 sequestration and biomass growth was affected by gas
      flow rate over the range 20-60ml/min and 40ml/min was found to maximize algal
      growth and CO2 sequestration. Moles of CO2 sequestered over 20h at a gas flow
      rate of 40ml/min was estimated using a novel rapid screening approach as 0.096
      and 0.036, respectively, for C. pyrenoidosa and S. abundans. At this gas flow
      rate the maximum growth rate was 4.9mgL(-1)h(-1) and 2.5mgL(-1)h(-1) for C.
      pyrenoidosa and S. abundans, respectively. The CO2 sequestration and growth rate
      were comparable at height/diameter ratio of 8 and 16. 

PMID- 25616747
TI  - [Sequential intervention with primary excision and Limberg plastic surgery
      procedure for treatment of sacrococcygeal pilonidal sinus : Results of a pilot
      study].
AB  - BACKGROUND: The current German S3 guidelines recommend radical excision for
      pilonidal sinus disease. Furthermore, the Karydakis operation and the plastic
      surgery procedure according to Limberg are also recommended. Contrary to the S2
      guidelines of 2008, these two plastic surgery procedures for coverage are
      recommended for the treatment of the first-time manifestation of this disease.
      Most studies on the classical Limberg plastic surgical procedure are comparative
      in nature and describe a simultaneous intervention from which patients with an
      abscess are excluded. AIM: The aim of this present study was to analyze the
      results of a sequential procedure including primary excision followed by a
      Limberg plastic surgery procedure for the treatment of acute abscesses and
      chronic pilonidal sinus disease. MATERIAL AND METHODS: From July 2010 to June
      2013 a total of 50 patients with pilonidal sinus disease were treated at the
      University Hospital Jena with an initial radical excision. In accordance with the
      Association of the Scientific Medical Societies in Germany (AWMF) guidelines
      which were valid during that time, patients were offered plastic surgery coverage
      for recurrence prophylaxis and in cases of recurrence a Limberg plastic surgery
      procedure was recommended. RESULTS: Of the 50 patients 22 opted for a Limberg
      plastic surgery procedure during the interval. The mean follow-up after the
      Limberg plastic surgery procedure was 20.1 months (range 2-36 months). During the
      follow-up period, there were no recurrences (0 %) but four major complications
      (18.2 %) and one minor complication (4.5 %) were observed. CONCLUSION: This
      concept can be applied in cases of acute abscess formation and in chronic
      pilonidal sinus disease. The patient's decision with respect to a Limberg plastic
      surgery procedure for recurrence prophylaxis does not have to be made
      immediately. In addition, the Limberg plastic surgery procedure is performed in
      an infection-free stage. The second inpatient stay, second surgical procedure and
      prolonged time off work are a disadvantage.

PMID- 25616749
TI  - The relationship between psychosocial features of emerging adulthood and
      substance use change motivation in youth.
AB  - Despite the peak prevalence of substance use and comorbid mental health problems
      during emerging adulthood little research has focused on understanding behavior
      change processes during this transitional period. This study extended Arnett's
      (2004) theory of the psychosocial features of emerging adulthood to explore how
      they may relate to treatment motivation (e.g., readiness to comply with
      treatment) and motivation to change (e.g., problem recognition and taking steps
      towards change). One hundred sixty-four youth presenting to outpatient substance
      abuse treatment completed questionnaires investigating problematic substance use,
      mental health, psychosocial features of emerging adulthood and motivation.
      Results of hierarchical regression analyses indicated that youth who perceived
      themselves as having greater responsibility towards others were more
      intrinsically motivated, recognized their substance use as problematic and were
      taking steps towards change. None of the other dimensions of emerging adulthood
      accounted for significant variance beyond relevant controls. Limitations,
      directions for future research and treatment implications are discussed. 

PMID- 25616750
TI  - A satisfaction survey of opioid-dependent patients with methadone maintenance
      treatment.
AB  - The aim of this study was to examine opioid-dependent patients' satisfaction with
      the methadone maintenance treatment (MMT) program in Malaysia and identify
      predictors of satisfaction. We used an interviewer-administered questionnaire
      developed and validated by Rankin Court, New South Wales, Australia. Of 502
      patients approached in 11 MMT centers in Malaysia, 425 agreed to participate
      giving a response rate of 85%. In terms of overall satisfaction, a high
      percentage of respondents (85%) were satisfied with the MMT services. A logistic
      regression analysis showed that only "centres" and marital status were associated
      with overall satisfaction and that being single (OR 3.31; 95% CI 1.52 to 7.20) or
      married (OR 4.06; 95% CI 1.76 to 9.38) was associated with higher odds of overall
      satisfaction compared to being divorced or separated. An analysis of the
      responses pertaining to the most desired changes required at the center found
      dosing hours, waiting area and staff shortages to be common. The findings
      acquired from this survey will be useful to attain a clearer perspective on what
      aspects of the MMT service need to be reviewed for the improvement of service
      delivery. 

PMID- 25616751
TI  - Esophageal introitus (with videos).

PMID- 25616752
TI  - Validation of the diagnostic accuracy of probe-based confocal laser
      endomicroscopy for the characterization of indeterminate biliary strictures:
      results of a prospective multicenter international study.
AB  - BACKGROUND: Characterization of indeterminate biliary strictures remains
      problematic. Tissue sampling is the criterion standard for confirming malignancy
      but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed
      excellent sensitivity in a registry; however, it has not been validated in a
      prospective study. OBJECTIVE: To prospectively validate pCLE in real time during
      ERCP for indeterminate biliary strictures. DESIGN: Prospective, international,
      multicenter study. SETTING: Six academic centers. PATIENTS: A total of 136
      patients with indeterminate biliary strictures. INTERVENTIONS: Investigators
      provided a presumptive diagnosis based on the patient history, ERCP impression,
      and pCLE during the procedure before and after tissue sampling results were
      available. A presumptive diagnosis also was made separately by a blinded
      investigator during ERCP and after tissue sampling to estimate care without pCLE.
      Follow-up was at least 6 months. MAIN OUTCOME MEASUREMENTS: Accuracy,
      sensitivity, and specificity during ERCP alone, ERCP with pCLE, and ERCP with
      pCLE and tissue sampling. RESULTS: A total of 112 patients were evaluated (71
      with malignant lesions). Tissue sampling alone was 56% sensitive, 100% specific,
      and 72% (95% confidence interval [CI], 63%-80%) accurate. pCLE with ERCP was 89%
      sensitive, 71% specific, and 82% (95% CI, 74%-89%) accurate. After tissue
      sampling returned, strictures could be characterized with 88% (95% CI, 81%-94%)
      accuracy. LIMITATIONS: No randomization of care maps. pCLE not blinded.
      CONCLUSION: pCLE provided a more accurate and sensitive diagnosis of
      cholangiocarcinoma compared with tissue sampling alone. Incorporation of pCLE
      into the diagnostic armamentarium of patients with indeterminate biliary
      strictures may allow for a more accurate assessment, potentially reducing delays
      in diagnosis and costly repeat testing. ( CLINICAL TRIAL REGISTRATION NUMBER:
      NCT01392274.).

PMID- 25616753
TI  - Distinguishing malignant from benign biliary strictures: can confocal laser
      endomicroscopy close the gap?

PMID- 25616754
TI  - Is plastic stenting for pancreatic cancer still relevant or obsolete in 2015?

PMID- 25616755
TI  - The role of EUS in ampullary lesions: is the answer black and white?

PMID- 25616756
TI  - The provision of ERCP services in the United States is a radiating concern.

PMID- 25616757
TI  - A multi-journal partnership to highlight joint first-authors of manuscripts.

PMID- 25616758
TI  - Thinking inside the box: 3-dimensional printing for interventional EUS training.

PMID- 25616759
TI  - EUS-guided celiac plexus neurolysis by using highly viscous phenol-glycerol as a
      neurolytic agent (with video).

PMID- 25616760
TI  - Response.

PMID- 25616761
TI  - Esophageal adenocarcinoma in Barrett's esophagus with low-grade dysplasia.

PMID- 25616762
TI  - A novel method of evaluating corrosive stricture during endoscopy.

PMID- 25616763
TI  - A new gustometer for taste testing in rodents.
AB  - In recent years, to circumvent the interpretive limitations associated with
      intake tests commonly used to assess taste function in rodents, investigators
      have developed devices called gustometers to deliver small volumes of taste
      samples and measure immediate responses, thereby increasing confidence that the
      behavior of the animal is under orosensory control. Most of these gustometers can
      be used to measure unconditioned licking behavior to stimuli presented for short
      durations and/or can be used to train the animal to respond to various fluid
      stimuli differentially so as to obtain a reward and/or avoid punishment.
      Psychometric sensitivity and discrimination functions can thus be derived. Here,
      we describe a new gustometer design, successfully used in behavioral experiments,
      that was guided by our experience with an older version used for over 2 decades.
      The new computer-controlled gustometer features no dead space in stimulus
      delivery lines, effective cleaning of the licking substrate, and the ability to
      measure licking without passing electrical current through the animal. The parts
      and dimensions are detailed, and the benefits and limitations of certain design
      features are discussed. Schematics for key circuits are provided as supplemental
      information. Accordingly, it should be possible to fabricate this device in a
      fashion customized for one's needs. 

PMID- 25616764
TI  - [Robotic-assisted radical prostatectomy].
AB  - BACKGROUND: Robot-assisted laparoscopic radical prostatectomy (RALP) has been
      rapidly adopted as a standard approach for surgical treatment of organ-confined
      prostate cancer. Despite additional costs, RALP seems to provide better
      functional and oncological outcomes and less blood loss compared to open radical
      prostatectomy (ORP). However, prospective randomized studies are still missing.
      PURPOSE: Based on the current literature, this review reports about the role of
      RALP in prostate cancer treatment. Its functional and oncologic outcomes as well
      as complication rates are compared to ORP. Particularly, the role of RALP in
      nonorgan-confined tumors will be discussed. RESULTS: Based on the current
      literature, RALP provides better continence and potency rates as compared to ORP.
      Moreover, the incidence of positive surgical margins seems to be reduced.
      However, there is conflicting data regarding the role of RALP in nonorgan
      confined prostate cancer. Regarding long-term oncologic outcomes, RALP seems to
      be comparable to ORP.

PMID- 25616765
TI  - [Sexuality after radical prostatectomy: Evaluation of erectile function and
      patient counseling regarding their sex life].
AB  - BACKGROUND: Patient counseling by using the IIEF to assess erectile function (EF)
      before and after radical prostatectomy (RPX) is only possible under limited
      circumstances. The aim of this study was to evaluate if the Erection Hardness
      Score (EHS) could be used in addition to the IIEF for the assessment of EF and
      patient preference regarding counseling for their sex life. MATERIAL AND METHODS:
      EF was evaluated in 307 patients 3-60 months after RPX using the IIEF-EF and EHS.
      Questionnaires assessed sexual activity/intercourse as well as satisfaction with
      sex life irrespective of EF (10-point Likert scale). Patients were further asked
      concerning development of new sexual methods independent of erection firm enough
      for penetration and further wishes regarding counseling for their sex life.
      RESULTS: Of 272 patients, 82.0% underwent bilateral nerve-sparing prostatectomy,
      30.5% (n=83; mean age: 68.1 years) had sexual intercourse and 41.9% (n=114) were
      sexually active. EH Scores 1-2 and 4 coincided with compatible IIEF-EF Scores 1
      21, and >= 26, respectively. Of the patients with an EHS of 3, 55.9% had an IIEF
      EF score that was notably lower. Of patients with sexual intercourse, 65.8% were
      satisfied with their sex life; 53.2% of sexually active patients were satisfied
      without sexual intercourse. Alternative methods were manual/oral stimulation,
      cuddling, and the use of vibrators. Patients request individually tailored,
      realistic counseling. CONCLUSION: The advantage of the EHS compared to the IIEF
      is that the erectile function can be assessed irrespective of sexual intercourse
      and sexual partner. Counseling should assist patients towards the attainment of a
      satisfying sex life-even without an erection.

PMID- 25616766
TI  - [Reduced morbidity in resection of residual tumors after chemotherapy for
      seminoma].
AB  - BACKGROUND: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is
      associated with complications and decreased adjunctive surgery. Little data are
      available concerning PC-RPLND in patients with advanced seminomas and residual
      retroperitoneal tumor lesions. We examined intra- and postoperative complications
      as well as the frequency of adjunctive surgeries in patients with seminoma and
      compared the data to a cohort of patients with non-seminomatous germ cell tumors
      (NSGCT) who underwent PC-RPLND. PATIENTS AND METHODS: In our retrospective
      analysis, 580 patients (43 patients with advanced seminomas and 537 patients with
      NSGCT) underwent PC-RPLND between 1989 and 2010. The surgical approach was
      preferred via midline incision or a thoracoabdominal approach depending on the
      location of the residual tumor. RESULTS: Of the 43 patients with seminoma, a
      total number of 13 adjunctive surgeries were performed in 7 patients. There were
      only three intraoperative complications, two postoperative complications
      (prolonged intestinal paralyses). There were no significant differences in
      adjunctive surgeries and postoperative complications (p=0.49 and p=0.133) between
      the two groups. There were significantly fewer intraoperative complications in
      favor of seminomas (p=0.001). CONCLUSION: PCRLND in seminomas and NSGCT is a
      demanding surgical intervention. In contrast to other series we did not find
      significant differences in the two patient groups concerning adjunctive surgeries
      and postoperative complications. The indication for PCLND in patients with
      seminoma is limited, but if necessary it can be performed safely in experienced
      centers.

PMID- 25616767
TI  - Test-retest reliability of a new questionnaire on the diet and eating behavior of
      one year old children.
AB  - BACKGROUND: As part of a sub-study in the ongoing Norwegian RCT 'Fit for
      Delivery', a new questionnaire, using a combination of food frequency, scale, and
      categorical questions to gather data on the diets and eating patterns of one year
      olds, was developed and tested for reliability by test-retest. RESULTS: Of 102
      parents recruited to the study, 94 completed both test and retest. Correlation
      coefficients (Spearman's r, and/or Cohen's kappa, where applicable) were high for
      all categories of question, with a mean value of 0.72 for Spearman's r for food
      frequency variables, and a mean value of 0.75 for Cohen's kappa for non-numeric
      variables such as breast feeding status, showing very high test-retest
      reliability. CONCLUSIONS: This newly developed diet and eating habit
      questionnaire had strong test-retest reliability in a test population similar to
      the study population, for which it was developed. This indicates that the
      questionnaire is reliable in this population.

PMID- 25616768
TI  - Genetics and Disease Expression in the CNGA3 Form of Achromatopsia: Steps on the
      Path to Gene Therapy.
AB  - PURPOSE: Achromatopsia (ACHM) is a congenital, autosomal recessive retinal
      disease that manifests cone dysfunction, reduced visual acuity and color vision,
      nystagmus, and photoaversion. Five genes are known causes of ACHM. The present
      study took steps toward performing a trial of gene therapy in ACHM by
      characterizing the genetics of ACHM in Israel and the Palestinian Territories and
      analyzing retinal function and structure in CNGA3 ACHM patients from the Israeli
      Palestinian population and US patients with other origins. DESIGN: Case series
      study. PARTICIPANTS: Patients with clinically suspected ACHM, cone dysfunction
      phenotypes, and unaffected family members were included. The protocol was
      approved by the local institutional review board and informed consent was
      obtained from all participants. METHODS: Genetic analyses included homozygosity
      mapping and exome sequencing. Phenotype was assessed with electroretinography
      (ERG), optical coherence tomography, psychophysics, and photoaversion testing.
      MAIN OUTCOME MEASURES: Single nucleotide polymorphism microarray, exome analysis,
      DNA sequence analysis, visual function testing including ERG, and photoaversion.
      RESULTS: We identified 148 ACHM patients from 57 Israeli and Palestinian
      families; there were 16 CNGA3 mutations (5 novel) in 41 families and 5 CNGB3
      mutations (1 novel) in 8 families. Two CNGA3 founder mutations underlie >50% of
      cases. These mutations lead to a high ACHM prevalence of ~1:5000 among Arab
      Muslims residing in Jerusalem. Rod ERG abnormalities (in addition to cone
      dysfunction) were detected in 59% of patients. Retinal structure in CNGA3 ACHM
      patients revealed persistent but abnormal foveal cones. Under dark- and light
      adapted conditions, patients use rod-mediated pathways. Photoaversion was readily
      demonstrated with transition from the dark to a dim light background.
      CONCLUSIONS: Among Israeli and Palestinian patients, CNGA3 mutations are the
      leading cause of ACHM. Retinal structural results support the candidacy of CNGA3
      ACHM for clinical trials for therapy of cone photoreceptors. Efficacy outcome
      measures would include chromatic light-adapted psychophysics, with attention to
      the photoreceptor basis of the response, and quantitation of photoaversion.

PMID- 25616769
TI  - Efficacy and toxicity of second-course ophthalmic artery chemosurgery for
      retinoblastoma.
AB  - OBJECTIVE: Assess the usefulness of second-course ophthalmic artery chemosurgery
      (OAC) for patients with intraocular retinoblastoma that recurred after prior OAC.
      This study evaluated the efficacy and toxicity of second-course OAC. DESIGN:
      Single-arm retrospective study of 29 eyes of 30 patients treated with second
      course OAC at Memorial Sloan Kettering Cancer Center between May 2006 and July
      2013, with a median follow-up of 25.9 months. PARTICIPANTS: Retinoblastoma
      patients who underwent a course of OAC, with a minimum of 2 months of progression
      free follow-up at monthly examinations, but who subsequently received additional
      OAC for recurrent tumor. METHODS: To determine efficacy, Kaplan-Meier survival
      estimates were generated and the Mantel-Cox test was used to compare curves. To
      determine toxicity, electroretinography (ERG) amplitudes were measured in
      response to 30-Hz photopic flicker stimulation before and after OAC treatment;
      systemic adverse events were graded according to the Common Terminology Criteria
      for Adverse Events version 4.0 (CTCAE 4.0). MAIN OUTCOME MEASURES: For efficacy,
      ocular progression-free survival, ocular event-free survival (e.g., enucleation,
      external-beam radiation, or intravitreal melphalan), and ocular survival. For
      toxicity, peak-to-peak comparisons between ERG studies before and after OAC
      treatment and CTCAE 4.0-graded systemic adverse events. RESULTS: Fifty percent of
      all recurrences were within 4.4 months and 90% were within 16 months of
      completion of the first course of OAC. The 2-year Kaplan-Meier ocular survival,
      event-free survival, and progression-free survival estimates after second-course
      OAC were 82.8% (95% confidence interval [CI], 60.1%-93.2%), 57.3% (95% CI, 36.1%
      73.7%), and 26.5% (95% CI, 11.0%-45.0%), respectively. All eyes without vitreous
      seeding were progression free, whereas eyes with vitreous seeding were associated
      significantly with worse ocular survival after second-course OAC (P = 0.03).
      After second-course OAC, 90% of eyes had stable or improved ERG responses. Of all
      evaluable cases, there was no increased risk of systemic toxicity during the
      second course compared with the initial course of OAC. CONCLUSIONS:
      Retinoblastoma eyes requiring second-course OAC after initial OAC treatment have
      good salvage rates, and the treatment has an acceptable ocular and systemic
      toxicity profile. However, these eyes often require additional (third- or fourth
      course) OAC or other treatment methods because of progression of disease after
      second-line OAC, particularly if vitreous seeds are present at the time of
      initial OAC failure.

PMID- 25616770
TI  - En bloc resection of the temporal bone and temporomandibular joint for advanced
      temporal bone carcinoma.
AB  - Advanced skin malignancies involving the temporal bone can involve the
      temporomandibular joint and glenoid fossa. Many of these tumors can be removed
      with a lateral temporal bone resection; however, extensive involvement of the
      glenoid fossa should include an en bloc resection of the temporal bone, glenoid
      fossa, and condyle. We describe a novel surgical approach that is an extension of
      a temporal bone resection that includes the glenoid fossa and condyle in an en
      bloc resection with the temporal bone. This procedure has been performed in 7
      patients with advanced carcinoma of the temporal bone involving the glenoid
      fossa. There were no short-term complications as a result of the surgical
      approach. The addition of a middle fossa craniotomy and inclusion of the glenoid
      fossa and condyle as part of an en bloc resection of the temporal bone can be
      performed safely. 

PMID- 25616771
TI  - Cx43 and mechanotransduction in bone.
AB  - Bone adaptation to changes in mechanical stimuli occurs by adjusting bone
      formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone
      mass. Osteocytes coordinate the actions of these cells on the bone surface by
      sensing mechanical forces and producing cytokines that increase or prevent
      osteoblast and osteoclast differentiation and function. Channels formed by
      connexins (Cxs) and, in particular, connexin 43 (Cx43) in osteoblasts and
      osteocytes are central part of this mechanism to control bone mass. Cx43
      hemichannels are opened by fluid flow and mediate the anti-apoptotic effect of
      mechanical stimulation in vitro, suggesting that Cx43 participates in
      mechanotransduction. However, mice lacking Cx43 in osteoblasts and/or osteocytes
      show an increased anabolic response to loading and decreased catabolic response
      to unloading. This evidence suggests that Cx43 channels expressed in osteoblastic
      cells are not required for the response to mechanical stimulation, but mediate
      the consequence of lack thereof. The molecular basis of these unexpected
      responses to mechanical stimulation is currently under investigation. 

PMID- 25616772
TI  - Diet, gut microbiome, and bone health.
AB  - Interactions between the environment, the gut microbiome, and host
      characteristics that influence bone health are beginning to be explored. This is
      the first area where functional benefits from diet-induced changes in the gut
      microbiome have been reported for healthy people. Several prebiotics that reach
      the lower intestine have resulted in an altered gut microbiome that is thought to
      enhance fermentation of the fibers to produce short-chain fatty acids. These
      changes are positively correlated with increases in fractional calcium absorption
      in adolescents and with increases in measures of bone density and strength in
      animal models. New methodologies are available to explore mechanisms and to
      refine intervention strategies. 

PMID- 25616773
TI  - [Plasma cells].
AB  - Plasma cells are specialized terminally differentiated B cells that synthesize
      and secrete antibodies to maintain humoral immunity. By the production of
      pathogenic antibodies, plasma cells contribute to the development of many
      conditions, such as autoimmune disorders, transplant rejection and allergies. Two
      different plasma cell compartments can independently generate different types of
      pathogenic antibodies: (1) short-lived plasmablasts (proliferating precursors of
      mature plasma cells) and plasma cells, which live only as long as B cells are
      activated. Consequently, these cells cause disease flares that respond to
      immunosuppressive drugs and B cell targeting therapies. (2) Long-lived non
      proliferating memory plasma cells, which survive in niches in bone marrow and
      inflamed tissues for months, years or a lifetime independent of B or T cell help
      or antigen contact. Because they do not respond to immunosuppressants or
      treatment targeting B cells, they are responsible for refractory chronic
      conditions. Therefore, long-lived memory plasma cells in particular have emerged
      as important therapeutic targets and strategies to target these cells are
      discussed in this article. So far long-lived plasma cells can only be depleted by
      immunoablative therapy with antithymocyte globulin in the setting of stem cell
      transplantation or by treatment with proteasome inhibitors approved for multiple
      myeloma. These strategies provide options for treating refractory autoantibody
      mediated diseases. One interesting approach aims at an antigen-specific
      elimination of target plasma cells without depleting the protective plasma cells
      responsible for maintaining humoral immunity. 

PMID- 25616774
TI  - Editorial overview: growth and development.

PMID- 25616775
TI  - The effect of lateral wall perforation on screw pull-out strength: a cadaveric
      study.
AB  - BACKGROUND: Lateral pedicle wall perforations occur frequently during pedicle
      screw insertion. Although it is known that such an occurrence decreases the screw
      pull-out strength, the effect has not been quantified biomechanically. MATERIALS
      AND METHODS: Twenty fresh cadaveric lumbar vertebrae were harvested, and the bone
      mineral density (BMD) of each was evaluated with dual-energy radiography
      absorptiometry (DEXA). Twenty matched, 6.5-mm pedicle screws were inserted in two
      different manners in two groups, the control group and the experimental group. In
      the control group, the pedicle screw was inserted in a standard fashion taking
      adequate precaution to ensure there was no perforation of the wall. In the
      experimental group, the pedicle screw was inserted such that its trajectory
      perforated the lateral wall. Group assignments were done randomly, and the
      maximal fixation strength was recorded for each screw pull-out test with a
      material-testing system (MTS 858 II). RESULTS: The average BMD for both groups
      was 0.850 g/cm(2) (0.788-0.912 g/cm(2)). The average (and standard deviation)
      maximal pull-out forces were 1,015.8 +/- 249.40 N for the experimental group and
      1,326.0 +/- 320.50 N for the control group. According to a paired t-test, the
      difference between the two groups was statistically significant (P < 0.001).
      CONCLUSION: The results of this study confirm that the maximal pull-out strength
      of pedicle screws decreases by approximately 23.4% when the lateral wall is
      perforated.

PMID- 25616776
TI  - Retrieval practice and spacing effects in young and older adults: An examination
      of the benefits of desirable difficulty.
AB  - In the present study, we examined how the function relating continued retrieval
      practice (e.g., one, three, or five tests) and long-term memory retention is
      modulated by desirable difficulty (R. A. Bjork, 1994). Of particular interest was
      how retrieval difficulty differed across young and older adults and across
      manipulations of lag (Exp. 1) and spacing (Exp. 2). To extend on previous
      studies, the acquisition phase response latency was used as a proxy for retrieval
      difficulty, and our analysis of final-test performance was conditionalized on
      acquisition phase retrieval success, to more directly examine the influence of
      desirable difficulty on retention. The results from Experiment 1 revealed that
      continued testing in the short-lag condition led to consistent increases in
      retention, whereas continued testing in the long-lag condition led to
      increasingly smaller benefits in retention for both age groups. The results from
      Experiment 2 revealed that repeated spaced testing enhanced retention relative to
      taking one spaced test, for both age groups; however, repeated massed testing
      only enhanced retention over taking one test for young adults. Across both
      experiments, the response latency results were overall consistent with an
      influence of desirable difficulty on retention. The discussion focuses on the
      role of desirable difficulty during encoding in producing the benefits of lag,
      spacing, and testing. 

PMID- 25616777
TI  - Training specificity and transfer in time and distance estimation.
AB  - Learning is often specific to the conditions of training, making it important to
      identify which aspects of the testing environment are crucial to be matched in
      the training environment. In the present study, we examined training specificity
      in time and distance estimation tasks that differed only in the focus of
      processing (FOP). External spatial cues were provided for the distance estimation
      task and for the time estimation task in one condition, but not in another. The
      presence of a concurrent alphabet secondary task was manipulated during training
      and testing in all estimation conditions in Experiment 1. For distance as well as
      for time estimation in both conditions, training of the primary estimation task
      was found to be specific to the presence of the secondary task. In Experiments 2
      and 3, we examined transfer between one estimation task and another, with no
      secondary task in either case. When all conditions were equal aside from the FOP
      instructions, including the presence of external spatial cues, Experiment 2
      showed "transfer" between tasks, suggesting that training might not be specific
      to the FOP. When the external spatial cues were removed from the time estimation
      task, Experiment 3 showed no transfer between time and distance estimations,
      suggesting that external task cues influenced the procedures used in the
      estimation tasks. 

PMID- 25616778
TI  - Learning and interactivity in solving a transformation problem.
AB  - Outside the psychologist's laboratory, thinking proceeds on the basis of a great
      deal of interaction with artefacts that are recruited to augment problem-solving
      skills. The role of interactivity in problem solving was investigated using a
      river-crossing problem. In Experiment 1A, participants completed the same problem
      twice, once in a low interactivity condition, and once in a high interactivity
      condition (with order counterbalanced across participants). Learning, as gauged
      in terms of latency to completion, was much more pronounced when the high
      interactivity condition was experienced second. When participants first completed
      the task in the high interactivity condition, transfer to the low interactivity
      condition during the second attempt was limited; Experiment 1B replicated this
      pattern of results. Participants thus showed greater facility to transfer their
      experience of completing the problem from a low to a high interactivity
      condition. Experiment 2 was designed to determine the amount of learning in a low
      and high interactivity condition; in this experiment participants completed the
      problem twice, but level of interactivity was manipulated between subjects.
      Learning was evident in both the low and high interactivity groups, but latency
      per move was significantly faster in the high interactivity group, in both
      presentations. So-called problem isomorphs instantiated in different task
      ecologies draw upon different skills and abilities; a distributed cognition
      analysis may provide a fruitful perspective on learning and transfer. 

PMID- 25616779
TI  - Over-the-counter anti-ageing topical agents and their ability to protect and
      repair photoaged skin.
AB  - Ultraviolet radiation (UVR)-induced photoageing of the skin is associated with
      characteristic clinical features including a sallow complexion, deep, coarse
      wrinkles and a loss of elasticity. Remodelling of the dermal extracellular matrix
      (ECM) with changes to fibrillar collagens, elastic fibres and glycosaminoglycans
      is likely to be a major contributing factor to these particular clinical signs.
      Over-the-counter (OTC) topical formulations are one popular management strategy
      for preventing and/or repairing photoaged skin, most commonly targeting wrinkles
      as these are often the most concerning clinical feature. Due to the cosmetic
      nature of such formulations, evidence of their clinical efficacy and mechanism of
      action is often limited. However, these formulations usually contain putative
      active ingredients which individually have been subject to in vitro and in vivo
      investigation for efficacy as photoageing interventions. This review highlights
      commonly found ingredients within OTC formulations and assesses the evidence for:
      (i) their efficacy in clinically and histologically improving photoaged skin;
      (ii) the potential mechanisms of action; and (iii) their ability to act
      synergistically with complementary ingredients to enhance the clinical outcome. 

PMID- 25616780
TI  - Age-related changes in resting energy expenditure in normal weight, overweight
      and obese men and women.
AB  - OBJECTIVES: Aging is associated with changes in resting energy expenditure (REE)
      and body composition. We investigated the association between age and changes in
      REE in men and women stratified by body mass index (BMI) categories (normal
      weight, overweight and obesity). We also examined whether the age-related decline
      in REE was explained by concomitant changes in body composition and lifestyle
      factors. STUDY DESIGN: Cross-sectional. MAIN OUTCOME MEASURES: 3442 adult
      participants (age range: 18-81 y; men/women: 977/2465) were included. The BMI
      range was 18.5-60.2 kg/m(2). REE was measured by indirect calorimetry in fasting
      conditions and body composition by bioelectrical impedance. Regression models
      were used to evaluate age-related changes in REE in subjects stratified by sex
      and BMI. Models were adjusted for body composition (fat mass, fat free mass),
      smoking, disease count and physical activity. RESULTS: In unadjusted models, the
      rate of decline in REE was highest in obese men (slope=-8.7+/-0.8 kcal/day/year)
      whereas the lowest rate of decline was observed in normal weight women (-2.9+/
      0.3 kcal/day/year). Gender differences were observed for the age of onset of REE
      adaptive changes (i.e., not accounted by age related changes in body composition
      and lifestyle factors). In women, adaptive changes appeared to occur in middle
      age (~47 y) across all BMI groups whereas changes seemed to be delayed in obese
      men (~54 y) compared to overweight (~43 y) and normal weight (~39 y) men.
      CONCLUSIONS: Sex and BMI influenced the rate and degree of the age-related
      decline in REE. Critical age windows have been identified for the onset of
      putative mechanisms of energy adaptation. These findings require confirmation in
      prospective studies.

PMID- 25616781
TI  - Composite cardiovascular risk scores and neuropsychological functioning: a meta
      analytic review.
AB  - BACKGROUND: The ability for patients to understand their risk for disease is
      important to early intervention and effective treatment. The link between
      individual cardiovascular risk factors and cognition has been well-established.
      PURPOSE: This study investigated the relationship between cognition and a
      combination of these factors through a single composite risk score. METHODS: This
      study quantitatively summarized the strength of the association between composite
      cardiovascular risk scores and cognitive test performance using meta-analytic
      methods. RESULTS: One hundred and nine effect sizes were obtained from 19 studies
      employing 54,564 participants. Composite risk scores showed a significant
      association (r=-0.16) with cognitive test performance. Cognitive domain and age
      did not significantly modify this relationship. CONCLUSIONS: Composite
      cardiovascular risk scores can be useful indicators of future cognition. The
      development of a dementia risk score using similar risk factors could aid in the
      assessment and lifestyle interventions of persons at risk for dementia.

PMID- 25616783
TI  - Persistence of spiromesifen in soil: influence of moisture, light, pH and organic
      amendment.
AB  - Persistence of spiromesifen in soil as affected by varying moisture, light,
      compost amendment, soil sterilization and pH in aqueous medium were studied.
      Degradation of spiromesifen in soil followed the first-order reaction kinetics.
      Effect of different moisture regimes indicated that spiromesifen dissipated
      faster in submerged soil (t 1/2 14.3-16.7 days) followed by field capacity (t 1/2
      18.7-20.0 days), and dry soil (t 1/2 21.9-22.9 days). Dissipation was faster in
      sterilized submerged (t 1/2 17.7 days) than in sterilized dry (t 1/2 35.8 days).
      Photo spiromesifen metabolite was not detected under different moisture regimes.
      After 30 days, enol spiromesifen metabolite was detected under submerged
      condition and was below detectable limit (<0.001 MUg g(-1)) after 90 days. Soil
      amendment compost (2.5 %) at field capacity enhanced dissipation of the
      insecticide, and half-life value was 14.3 against 22.4 days without compost
      amendment. Under different pH condition, residues persisted in water with half
      life values 5.7 to 12.5 days. Dissipation in water was faster at pH 9.0 (t 1/2
      5.7 days), followed by pH 4.0 (t 1/2 9.7 days) and pH 7.2 (t 1/2 12.5 days).
      Exposure of spiromesifen to different light conditions indicated that it was more
      prone to degradation under UV light (t 1/2 3-4 days) than sunlight exposure (t
      1/2 5.2-8.1 days). Under sunlight exposure, photo spiromesifen metabolite was
      detected after 10 and 15 days as compared to 3 and 5 days under UV light
      exposure.

PMID- 25616782
TI  - Occurrence and potential health risk of Cryptosporidium and Giardia in different
      water catchments in Belgium.
AB  - Human wastewater and livestock can contribute to contamination of surface water
      with Cryptosporidium and Giardia. In countries where a substantial proportion of
      drinking water is produced from surface water, e.g., Belgium, this poses a
      constant threat on drinking water safety. Our objective was to monitor the
      presence of Cryptosporidium and Giardia in different water catchment sites in
      Belgium and to discriminate between (oo)cysts from human or animal origin using
      genotyping. Monthly samples were collected from raw water and purified drinking
      water at four catchment sites. Cryptosporidium and Giardia were detected using
      USEPA method 1623 and positive samples were genotyped. No contamination was found
      in purified water at any site. In three catchments, only low numbers of (oo)cysts
      were recovered from raw water samples (<1/liter), but raw water samples from one
      catchment site were frequently contaminated with Giardia (92 %) and
      Cryptosporidium (96 %), especially in winter and spring. Genotyping of Giardia in
      38 water samples identified the presence of Giardia duodenalis assemblage AI,
      AII, BIV, BIV-like, and E. Cryptosporidium andersoni, Cryptosporidium suis,
      Cryptosporidium horse genotype, Cryptosporidium parvum, and Cryptosporidium
      hominis were detected. The genotyping results suggest that agriculture may be a
      more important source of surface water contamination than human waste in this
      catchment. In catchment sites with contaminated surface water, such as the
      Blankaart, continuous monitoring of treated water for the presence of
      Cryptosporidium and Giardia would be justified and (point) sources of surface
      water contamination should be identified.

PMID- 25616784
TI  - Impact of marble industry effluents on water and sediment quality of Barandu
      River in Buner District, Pakistan.
AB  - Industries play an important role in improving the living standard but at the
      same time cause several environmental problems. Therefore, it is necessary to
      evaluate the impact of industries on the quality of environment. In the present
      study, the impact of marble industry effluents on water and sediment quality of
      Barandu River in Buner District, Pakistan was evaluated. Water and sediment
      samples were collected at three different sampling sites (upstream, industrial,
      and downstream sites) from Barandu River and their physicochemical properties
      were inter-compared. In addition, different marble stones and mix water
      (wastewater) from marble industry were analyzed. The measured physicochemical
      parameters of river water including pH, electrical conductivity (EC), alkalinity,
      total hardness, Ca and Mg hardness, total dissolved solid (TDS), total suspended
      solids (TSS), sulfates (SO4 (2-)), sodium (Na(+)), potassium (K(+)), nitrites
      (NO2 (-)), nitrate (NO3 (-)), chloride (Cl(-)), calcium (Ca(2+)), and magnesium
      (Mg(2+)) were found to be significantly altered by effluent discharges of marble
      industries. Similarly, heavy metal concentrations in both water and sediments of
      the river were significantly increased by marble industry wastewater. It is
      concluded that large quantities of different pollutants are added to Barandu
      River due to direct disposal of marble industry effluents which degrades its
      quality. Therefore, it is recommended that direct disposal of marble industry
      wastewater should be banned and all effluents must be properly treated before
      discharging in the river water.

PMID- 25616785
TI  - A multi-criteria decision making approach to identify a vaccine formulation.
AB  - This article illustrates the use of a multi-criteria decision making approach,
      based on desirability functions, to identify an appropriate adjuvant composition
      for an influenza vaccine to be used in elderly. The proposed adjuvant system
      contained two main elements: monophosphoryl lipid and alpha-tocopherol with
      squalene in an oil/water emulsion. The objective was to elicit a stronger immune
      response while maintaining an acceptable reactogenicity and safety profile. The
      study design, the statistical models, the choice of the desirability functions,
      the computation of the overall desirability index, and the assessment of the
      robustness of the ranking are all detailed in this manuscript. 

PMID- 25616786
TI  - Left-handed DNA challenge.

PMID- 25616787
TI  - Syntrophic growth of Desulfovibrio alaskensis requires genes for H2 and formate
      metabolism as well as those for flagellum and biofilm formation.
AB  - In anaerobic environments, mutually beneficial metabolic interactions between
      microorganisms (syntrophy) are essential for oxidation of organic matter to
      carbon dioxide and methane. Syntrophic interactions typically involve a
      microorganism degrading an organic compound to primary fermentation by-products
      and sources of electrons (i.e., formate, hydrogen, or nanowires) and a partner
      producing methane or respiring the electrons via alternative electron accepting
      processes. Using a transposon gene mutant library of the sulfate-reducing
      Desulfovibrio alaskensis G20, we screened for mutants incapable of serving as the
      electron-accepting partner of the butyrate-oxidizing bacterium, Syntrophomonas
      wolfei. A total of 17 gene mutants of D. alaskensis were identified as incapable
      of serving as the electron-accepting partner. The genes identified predominantly
      fell into three categories: membrane surface assembly, flagellum-pilus synthesis,
      and energy metabolism. Among these genes required to serve as the electron
      accepting partner, the glycosyltransferase, pilus assembly protein (tadC), and
      flagellar biosynthesis protein showed reduced biofilm formation, suggesting that
      each of these components is involved in cell-to-cell interactions. Energy
      metabolism genes encoded proteins primarily involved in H2 uptake and electron
      cycling, including a rhodanese-containing complex that is phylogenetically
      conserved among sulfate-reducing Deltaproteobacteria. Utilizing an mRNA
      sequencing approach, analysis of transcript abundance in wild-type axenic and
      cocultures confirmed that genes identified as important for serving as the
      electron-accepting partner were more highly expressed under syntrophic
      conditions. The results imply that sulfate-reducing microorganisms require
      flagellar and outer membrane components to effectively couple to their syntrophic
      partners; furthermore, H2 metabolism is essential for syntrophic growth of D.
      alaskensis G20. 

PMID- 25616788
TI  - Extrahuman epidemiology of Acinetobacter baumannii in Lebanon.
AB  - The presence of Acinetobacter baumannii outside hospitals is still a
      controversial issue. The objective of our study was to explore the extrahospital
      epidemiology of A. baumannii in Lebanon. From February 2012 to October 2013, a
      total of 73 water samples, 51 soil samples, 37 raw cow milk samples, 50 cow meat
      samples, 7 raw cheese samples, and 379 animal samples were analyzed by cultural
      methods for the presence of A. baumannii. Species identification was performed by
      rpoB gene sequencing. Antibiotic susceptibility was investigated, and the A.
      baumannii population was studied by two genotyping approaches: multilocus
      sequence typing (MLST) and blaOXA-51 sequence-based typing (SBT). A. baumannii
      was detected in 6.9% of water samples, 2.7% of milk samples, 8.0% of meat
      samples, 14.3% of cheese samples, and 7.7% of animal samples. All isolates showed
      a susceptible phenotype against most of the antibiotics tested and lacked
      carbapenemase-encoding genes, except one that harbored a blaOXA-143 gene. MLST
      analysis revealed the presence of 36 sequence types (STs), among which 24 were
      novel STs reported for the first time in this study. blaOXA-51 SBT showed the
      presence of 34 variants, among which 21 were novel and all were isolated from
      animal origins. Finally, 30 isolates had new partial rpoB sequences and were
      considered putative new Acinetobacter species. In conclusion, animals can be a
      potential reservoir for A. baumannii and the dissemination of new emerging
      carbapenemases. The roles of the novel animal clones identified in community
      acquired infections should be investigated. 

PMID- 25616790
TI  - Long-term study of Vibrio parahaemolyticus prevalence and distribution in New
      Zealand shellfish.
AB  - The food-borne pathogen Vibrio parahaemolyticus has been reported as being
      present in New Zealand (NZ) seawaters, but there have been no reported outbreaks
      of food-borne infection from commercially grown NZ seafood. Our study determined
      the current incidence of V. parahaemolyticus in NZ oysters and Greenshell mussels
      and the prevalence of V. parahaemolyticus tdh and trh strains. Pacific (235) and
      dredge (21) oyster samples and mussel samples (55) were obtained from commercial
      shellfish-growing areas between December 2009 and June 2012. Total V.
      parahaemolyticus numbers and the presence of pathogenic genes tdh and trh were
      determined using the FDA most-probable-number (MPN) method and confirmed using
      PCR analysis. In samples from the North Island of NZ, V. parahaemolyticus was
      detected in 81% of Pacific oysters and 34% of mussel samples, while the numbers
      of V. parahaemolyticus tdh and trh strains were low, with just 3/215 Pacific
      oyster samples carrying the tdh gene. V. parahaemolyticus organisms carrying tdh
      and trh were not detected in South Island samples, and V. parahaemolyticus was
      detected in just 1/21 dredge oyster and 2/16 mussel samples. Numbers of V.
      parahaemolyticus organisms increased when seawater temperatures were high, the
      season when most commercial shellfish-growing areas are not harvested. The
      numbers of V. parahaemolyticus organisms in samples exceeded 1,000 MPN/g only
      when the seawater temperatures exceeded 19 degrees C, so this environmental
      parameter could be used as a trigger warning of potential hazard. There is some
      evidence that the total V. parahaemolyticus numbers increased compared with those
      reported from a previous 1981 to 1984 study, but the analytical methods differed
      significantly. 

PMID- 25616789
TI  - Genotype-specific variation in the structure of root fungal communities is
      related to chickpea plant productivity.
AB  - Increasing evidence supports the existence of variations in the association of
      plant roots with symbiotic fungi that can improve plant growth and inhibit
      pathogens. However, it is unclear whether intraspecific variations in the
      symbiosis exist among plant cultivars and if they can be used to improve crop
      productivity. In this study, we determined genotype-specific variations in the
      association of chickpea roots with soil fungal communities and evaluated the
      effect of root mycota on crop productivity. A 2-year field experiment was
      conducted in southwestern Saskatchewan, the central zone of the chickpea growing
      region of the Canadian prairie. The effects of 13 cultivars of chickpea,
      comprising a wide range of phenotypes and genotypes, were tested on the structure
      of root-associated fungal communities based on internal transcribed spacer (ITS)
      and 18S rRNA gene markers using 454 amplicon pyrosequencing. Chickpea cultivar
      significantly influenced the structure of the root fungal community. The
      magnitude of the effect varied with the genotypes evaluated, and effects were
      consistent across years. For example, the roots of CDC Corrine, CDC Cory, and CDC
      Anna hosted the highest fungal diversity and CDC Alma and CDC Xena the lowest.
      Fusarium sp. was dominant in chickpea roots but was less abundant in CDC Corrine
      than the other cultivars. A bioassay showed that certain of these fungal taxa,
      including Fusarium species, can reduce the productivity of chickpea, whereas
      Trichoderma harzianum can increase chickpea productivity. The large variation in
      the profile of chickpea root mycota, which included growth-promoting and 
      inhibiting species, supports the possibility of improving the productivity of
      chickpea by improving its root mycota in chickpea genetic improvement programs
      using traditional breeding techniques. 

PMID- 25616791
TI  - The global regulator CodY in Streptococcus thermophilus controls the metabolic
      network for escalating growth in the milk environment.
AB  - CodY is a transcriptional regulator conserved in the low-GC group of Gram
      positive bacteria. In this work, we demonstrated the presence in Streptococcus
      thermophilus ST2017 of a functional member of the CodY family of global
      regulatory proteins, S. thermophilus CodY (CodYSt). The CodYSt regulon was
      identified by transcriptome analysis; it consisted predominantly of genes
      involved in amino acid metabolism but also included genes involved in several
      other cellular processes, including carbon metabolism, nutrient transport, and
      stress response. It was revealed that CodYSt repressed the transformation of the
      central metabolic pathway to amino acid metabolism and improved lactose
      utilization. Furthermore, the glutamate dehydrogenase gene (gdhA), repressed by
      CodYSt, was suggested to coordinate the interconversion between carbon metabolism
      and amino acid metabolism and to play an important role on the optimal growth of
      S. thermophilus ST2017 in milk. A conserved CodYSt box
      [AA(T/A)(A/T)TTCTGA(A/C)AATT] was indeed required for in vitro binding of CodYSt
      to the target regions of DNA. These results provided evidence for the function of
      CodYSt, by which this strain coordinately regulates its various metabolic
      pathways so as to adapt to the milk environment. 

PMID- 25616792
TI  - Oseltamivir-resistant influenza A (H1N1) virus strain with an H274Y mutation in
      neuraminidase persists without drug pressure in infected mallards.
AB  - Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging
      human IAVs often contain gene segments from avian viruses. The active drug
      metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu
      for influenza pandemic preparedness, is not removed by conventional sewage
      treatment and has been detected in river water. There, it may exert evolutionary
      pressure on avian IAV in waterfowl, resulting in the development of resistant
      viral variants. A resistant avian IAV can circulate among wild birds only if
      resistance does not restrict viral fitness and if the resistant virus can persist
      without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos)
      study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y
      mutation in the neuraminidase (NA-H274Y) could retain resistance while drug
      pressure was gradually removed. Successively infected mallards were exposed to
      decreasing levels of OC, and fecal samples were analyzed for the neuraminidase
      sequence and phenotypic resistance. No reversion to wild-type virus was observed
      during the experiment, which included 17 days of viral transmission among 10
      ducks exposed to OC concentrations below resistance induction levels. We conclude
      that resistance in avian IAV that is induced by exposure of the natural host to
      OC can persist in the absence of the drug. Thus, there is a risk that human
      pathogenic IAVs that evolve from IAVs circulating among wild birds may contain
      resistance mutations. An oseltamivir-resistant pandemic IAV would pose a
      substantial public health threat. Therefore, our observations underscore the need
      for prudent oseltamivir use, upgraded sewage treatment, and surveillance for
      resistant IAVs in wild birds. 

PMID- 25616793
TI  - Different bacterial populations associated with the roots and rhizosphere of rice
      incorporate plant-derived carbon.
AB  - Microorganisms associated with the roots of plants have an important function in
      plant growth and in soil carbon sequestration. Rice cultivation is the second
      largest anthropogenic source of atmospheric CH4, which is a significant
      greenhouse gas. Up to 60% of fixed carbon formed by photosynthesis in plants is
      transported below ground, much of it as root exudates that are consumed by
      microorganisms. A stable isotope probing (SIP) approach was used to identify
      microorganisms using plant carbon in association with the roots and rhizosphere
      of rice plants. Rice plants grown in Italian paddy soil were labeled with (13)CO2
      for 10 days. RNA was extracted from root material and rhizosphere soil and
      subjected to cesium gradient centrifugation followed by 16S rRNA amplicon
      pyrosequencing to identify microorganisms enriched with (13)C. Thirty operational
      taxonomic units (OTUs) were labeled and mostly corresponded to Proteobacteria (13
      OTUs) and Verrucomicrobia (8 OTUs). These OTUs were affiliated with the
      Alphaproteobacteria, Betaproteobacteria, and Deltaproteobacteria classes of
      Proteobacteria and the "Spartobacteria" and Opitutae classes of Verrucomicrobia.
      In general, different bacterial groups were labeled in the root and rhizosphere,
      reflecting different physicochemical characteristics of these locations. The
      labeled OTUs in the root compartment corresponded to a greater proportion of the
      16S rRNA sequences (~20%) than did those in the rhizosphere (~4%), indicating
      that a proportion of the active microbial community on the roots greater than
      that in the rhizosphere incorporated plant-derived carbon within the time frame
      of the experiment. 

PMID- 25616794
TI  - In vivo selection to identify bacterial strains with enhanced ecological
      performance in synbiotic applications.
AB  - One strategy for enhancing the establishment of probiotic bacteria in the human
      intestinal tract is via the parallel administration of a prebiotic, which is
      referred to as a synbiotic. Here we present a novel method that allows a rational
      selection of putative probiotic strains to be used in synbiotic applications: in
      vivo selection (IVS). This method consists of isolating candidate probiotic
      strains from fecal samples following enrichment with the respective prebiotic. To
      test the potential of IVS, we isolated bifidobacteria from human subjects who
      consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A
      retrospective analysis of the fecal microbiota of one subject revealed an 8-fold
      enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS
      administration. The functionality of GOS to support the establishment of IVS-1 in
      the gastrointestinal tract was then evaluated in rats administered the bacterial
      strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific
      quantitative real-time PCR showed that the addition of GOS increased B.
      adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to
      rats receiving only the probiotic. Illumina 16S rRNA sequencing not only
      confirmed the increased establishment of IVS-1 in the intestine but also revealed
      that the strain was able to outcompete the resident Bifidobacterium population
      when provided with GOS. In conclusion, this study demonstrated that IVS can be
      used to successfully formulate a synergistic synbiotic that can substantially
      enhance the establishment and competitiveness of a putative probiotic strain in
      the gastrointestinal tract. 

PMID- 25616795
TI  - Anthranilate deteriorates the structure of Pseudomonas aeruginosa biofilms and
      antagonizes the biofilm-enhancing indole effect.
AB  - Anthranilate and indole are alternative degradation products of tryptophan,
      depending on the bacterial species. While indole enhances the biofilm formation
      of Pseudomonas aeruginosa, we found that anthranilate, the tryptophan degradation
      product of P. aeruginosa, had an opposite effect on P. aeruginosa biofilm
      formation, in which anthranilate deteriorated the mushroom structure of biofilm.
      The anthranilate effect on biofilm formation was differentially exerted depending
      on the developmental stage and the presence of shear force. Anthranilate slightly
      accelerated the initial attachment of P. aeruginosa at the early stage of biofilm
      development and appeared to build more biofilm without shear force. But
      anthranilate weakened the biofilm structure in the late stage, deteriorating the
      mushroom structure of biofilms with shear force to make a flat biofilm. To
      investigate the interplay of anthranilate with indole in biofilm formation,
      biofilms were cotreated with anthranilate and indole, and the results showed that
      anthranilate antagonized the biofilm-enhancing effect of indole. Anthranilate was
      able to deteriorate the preformed biofilm. The effect of anthranilate and indole
      on biofilm formation was quorum sensing independent. AntR, a regulator of
      anthranilate-degrading metabolism was synergistically activated by cotreatment
      with anthranilate and indole, suggesting that indole might enhance biofilm
      formation by facilitating the degradation of anthranilate. Anthranilate slightly
      but significantly affected the cyclic diguaniylate (c-di-GMP) level and
      transcription of major extracellular polysaccharide (Psl, Pel, and alginate)
      operons. These results suggest that anthranilate may be a promising antibiofilm
      agent and antagonize the effect of indole on P. aeruginosa biofilm formation. 

PMID- 25616796
TI  - Fungal communities respond to long-term CO2 elevation by community reassembly.
AB  - Fungal communities play a major role as decomposers in the Earth's ecosystems.
      Their community-level responses to elevated CO2 (eCO2), one of the major global
      change factors impacting ecosystems, are not well understood. Using 28S rRNA gene
      amplicon sequencing and co-occurrence ecological network approaches, we analyzed
      the response of soil fungal communities in the BioCON (biodiversity, CO2, and N
      deposition) experimental site in Minnesota, USA, in which a grassland ecosystem
      has been exposed to eCO2 for 12 years. Long-term eCO2 did not significantly
      change the overall fungal community structure and species richness, but
      significantly increased community evenness and diversity. The relative abundances
      of 119 operational taxonomic units (OTU; ~27% of the total captured sequences)
      were changed significantly. Significantly changed OTU under eCO2 were associated
      with decreased overall relative abundance of Ascomycota, but increased relative
      abundance of Basidiomycota. Co-occurrence ecological network analysis indicated
      that eCO2 increased fungal community network complexity, as evidenced by higher
      intermodular and intramodular connectivity and shorter geodesic distance. In
      contrast, decreased connections for dominant fungal species were observed in the
      eCO2 network. Community reassembly of unrelated fungal species into highly
      connected dense modules was observed. Such changes in the co-occurrence network
      topology were significantly associated with altered soil and plant properties
      under eCO2, especially with increased plant biomass and NH4 (+) availability.
      This study provided novel insights into how eCO2 shapes soil fungal communities
      in grassland ecosystems. 

PMID- 25616797
TI  - Large fractions of CO2-fixing microorganisms in pristine limestone aquifers
      appear to be involved in the oxidation of reduced sulfur and nitrogen compounds.
AB  - The traditional view of the dependency of subsurface environments on surface
      derived allochthonous carbon inputs is challenged by increasing evidence for the
      role of lithoautotrophy in aquifer carbon flow. We linked information on
      autotrophy (Calvin-Benson-Bassham cycle) with that from total microbial community
      analysis in groundwater at two superimposed-upper and lower-limestone groundwater
      reservoirs (aquifers). Quantitative PCR revealed that up to 17% of the microbial
      population had the genetic potential to fix CO2 via the Calvin cycle, with
      abundances of cbbM and cbbL genes, encoding RubisCO (ribulose-1,5-bisphosphate
      carboxylase/oxygenase) forms I and II, ranging from 1.14 * 10(3) to 6 * 10(6)
      genes liter(-1) over a 2-year period. The structure of the active microbial
      communities based on 16S rRNA transcripts differed between the two aquifers, with
      a larger fraction of heterotrophic, facultative anaerobic, soil-related groups in
      the oxygen-deficient upper aquifer. Most identified CO2-assimilating phylogenetic
      groups appeared to be involved in the oxidation of sulfur or nitrogen compounds
      and harbored both RubisCO forms I and II, allowing efficient CO2 fixation in
      environments with strong oxygen and CO2 fluctuations. The genera Sulfuricella and
      Nitrosomonas were represented by read fractions of up to 78 and 33%,
      respectively, within the cbbM and cbbL transcript pool and accounted for 5.6 and
      3.8% of 16S rRNA sequence reads, respectively, in the lower aquifer. Our results
      indicate that a large fraction of bacteria in pristine limestone aquifers has the
      genetic potential for autotrophic CO2 fixation, with energy most likely provided
      by the oxidation of reduced sulfur and nitrogen compounds. 

PMID- 25616798
TI  - The growing season, but not the farming system, is a food safety risk determinant
      for leafy greens in the mid-Atlantic region of the United States.
AB  - Small- and medium-size farms in the mid-Atlantic region of the United States use
      varied agricultural practices to produce leafy greens during spring and fall, but
      the impact of preharvest practices on food safety risk remains unclear. To assess
      farm-level risk factors, bacterial indicators, Salmonella enterica, and Shiga
      toxin-producing Escherichia coli (STEC) from 32 organic and conventional farms
      were analyzed. A total of 577 leafy greens, irrigation water, compost, field
      soil, and pond sediment samples were collected. Salmonella was recovered from
      2.2% of leafy greens (n = 369) and 7.7% of sediment (n = 13) samples. There was
      an association between Salmonella recovery and growing season (fall versus
      spring) (P = 0.006) but not farming system (organic or conventional) (P = 0.920)
      or region (P = 0.991). No STEC was isolated. In all, 10% of samples were positive
      for E. coli: 6% of leafy greens, 18% of irrigation water, 10% of soil, 38% of
      sediment, and 27% of compost samples. Farming system was not a significant factor
      for levels of E. coli or aerobic mesophiles on leafy greens but was a significant
      factor for total coliforms (TC) (P < 0.001), with higher counts from organic farm
      samples. Growing season was a factor for aerobic mesophiles on leafy greens (P =
      0.004), with higher levels in fall than in spring. Water source was a factor for
      all indicator bacteria (P < 0.001), and end-of-line groundwater had marginally
      higher TC counts than source samples (P = 0.059). Overall, the data suggest that
      seasonal events, weather conditions, and proximity of compost piles might be
      important factors contributing to microbial contamination on farms growing leafy
      greens. 

PMID- 25616800
TI  - Phylogeny of intestinal ciliates, including Charonina ventriculi, and comparison
      of microscopy and 18S rRNA gene pyrosequencing for rumen ciliate community
      structure analysis.
AB  - The development of high-throughput methods, such as the construction of 18S rRNA
      gene clone or pyrosequencing libraries, has allowed evaluation of ciliate
      community composition in hundreds of samples from the rumen and other intestinal
      habitats. However, several genera of mammalian intestinal ciliates have been
      described based only on morphological features and, to date, have not been
      identified using molecular methods. Here, we isolated single cells of one of the
      smallest but widely distributed intestinal ciliates, Charonina ventriculi, and
      sequenced its 18S rRNA gene. We verified the sequence in a full-cycle rRNA
      approach using fluorescence in situ hybridization and thereby assigned an 18S
      rRNA gene sequence to this species previously known only by its morphology. Based
      on its full-length 18S rRNA gene sequence, Charonina ventriculi was positioned
      within the phylogeny of intestinal ciliates in the subclass Trichostomatia. The
      taxonomic framework derived from this phylogeny was used for taxonomic assignment
      of trichostome ciliate 18S rRNA gene sequence data stemming from high-throughput
      amplicon pyrosequencing of rumen-derived DNA samples. The 18S rRNA gene-based
      ciliate community structure was compared to that obtained from microscopic counts
      using the same samples. Both methods allowed identification of dominant members
      of the ciliate communities and classification of the rumen ciliate community into
      one of the types first described by Eadie in 1962. Notably, each method is
      associated with advantages and disadvantages. Microscopy is a highly accurate
      method for evaluation of total numbers or relative abundances of different
      ciliate genera in a sample, while 18S rRNA gene pyrosequencing represents a
      valuable alternative for comparison of ciliate community structure in a large
      number of samples from different animals or treatment groups. 

PMID- 25616801
TI  - Methanobactin from Methylocystis sp. strain SB2 affects gene expression and
      methane monooxygenase activity in Methylosinus trichosporium OB3b.
AB  - Methanotrophs can express a cytoplasmic (soluble) methane monooxygenase (sMMO) or
      membrane-bound (particulate) methane monooxygenase (pMMO). Expression of these
      MMOs is strongly regulated by the availability of copper. Many methanotrophs have
      been found to synthesize a novel compound, methanobactin (Mb), that is
      responsible for the uptake of copper, and methanobactin produced by Methylosinus
      trichosporium OB3b plays a key role in controlling expression of MMO genes in
      this strain. As all known forms of methanobactin are structurally similar, it was
      hypothesized that methanobactin from one methanotroph may alter gene expression
      in another. When Methylosinus trichosporium OB3b was grown in the presence of 1
      MUM CuCl2, expression of mmoX, encoding a subunit of the hydroxylase component of
      sMMO, was very low. mmoX expression increased, however, when methanobactin from
      Methylocystis sp. strain SB2 (SB2-Mb) was added, as did whole-cell sMMO activity,
      but there was no significant change in the amount of copper associated with M.
      trichosporium OB3b. If M. trichosporium OB3b was grown in the absence of CuCl2,
      the mmoX expression level was high but decreased by several orders of magnitude
      if copper prebound to SB2-Mb (Cu-SB2-Mb) was added, and biomass-associated copper
      was increased. Exposure of Methylosinus trichosporium OB3b to SB2-Mb had no
      effect on expression of mbnA, encoding the polypeptide precursor of methanobactin
      in either the presence or absence of CuCl2. mbnA expression, however, was reduced
      when Cu-SB2-Mb was added in both the absence and presence of CuCl2. These data
      suggest that methanobactin acts as a general signaling molecule in methanotrophs
      and that methanobactin "piracy" may be commonplace. 

PMID- 25616802
TI  - Reassessment of the transhydrogenase/malate shunt pathway in Clostridium
      thermocellum ATCC 27405 through kinetic characterization of malic enzyme and
      malate dehydrogenase.
AB  - Clostridium thermocellum produces ethanol as one of its major end products from
      direct fermentation of cellulosic biomass. Therefore, it is viewed as an
      attractive model for the production of biofuels via consolidated bioprocessing.
      However, a better understanding of the metabolic pathways, along with their
      putative regulation, could lead to improved strategies for increasing the
      production of ethanol. In the absence of an annotated pyruvate kinase in the
      genome, alternate means of generating pyruvate have been sought. Previous
      proteomic and transcriptomic work detected high levels of a malate dehydrogenase
      and malic enzyme, which may be used as part of a malate shunt for the generation
      of pyruvate from phosphoenolpyruvate. The purification and characterization of
      the malate dehydrogenase and malic enzyme are described in order to elucidate
      their putative roles in malate shunt and their potential role in C. thermocellum
      metabolism. The malate dehydrogenase catalyzed the reduction of oxaloacetate to
      malate utilizing NADH or NADPH with a kcat of 45.8 s(-1) or 14.9 s(-1),
      respectively, resulting in a 12-fold increase in catalytic efficiency when using
      NADH over NADPH. The malic enzyme displayed reversible malate decarboxylation
      activity with a kcat of 520.8 s(-1). The malic enzyme used NADP(+) as a cofactor
      along with NH4 (+) and Mn(2+) as activators. Pyrophosphate was found to be a
      potent inhibitor of malic enzyme activity, with a Ki of 0.036 mM. We propose a
      putative regulatory mechanism of the malate shunt by pyrophosphate and NH4 (+)
      based on the characterization of the malate dehydrogenase and malic enzyme. 

PMID- 25616804
TI  - Elucidation of echovirus 30's origin and transmission during the 2012 aseptic
      meningitis outbreak in Guangdong, China, through continuing environmental
      surveillance.
AB  - An aseptic meningitis outbreak occurred in Luoding City of Guangdong, China, in
      2012, and echovirus type 30 (ECHO30) was identified as the major causative
      pathogen. Environmental surveillance indicated that ECHO30 was detected in the
      sewage of a neighboring city, Guangzhou, from 2010 to 2012 and also in Luoding
      City sewage samples (6/43, 14%) collected after the outbreak. In order to track
      the potential origin of the outbreak viral strains, we sequenced the VP1 genes of
      29 viral strains from clinical patients and environmental samples. Sequence
      alignments and phylogenetic analyses based on VP1 gene sequences revealed that
      virus strains isolated from the sewage of Guangzhou and Luoding cities matched
      well the clinical strains from the outbreak, with high nucleotide sequence
      similarity (98.5% to 100%) and similar cluster distribution. Five ECHO30 clinical
      strains were clustered with the Guangdong environmental strains but diverged from
      strains from other regions, suggesting that this subcluster of viruses most
      likely originated from the circulating virus in Guangdong rather than having been
      more recently imported from other regions. These findings underscore the
      importance of long-term, continuous environmental surveillance and genetic
      analysis to monitor circulating enteroviruses. 

PMID- 25616803
TI  - Large-Scale 13C flux profiling reveals conservation of the Entner-Doudoroff
      pathway as a glycolytic strategy among marine bacteria that use glucose.
AB  - Marine bacteria form one of the largest living surfaces on Earth, and their
      metabolic activity is of fundamental importance for global nutrient cycling.
      Here, we explored the largely unknown intracellular pathways in 25 microbes
      representing different classes of marine bacteria that use glucose:
      Alphaproteobacteria, Gammaproteobacteria, and Flavobacteriia of the Bacteriodetes
      phylum. We used (13)C isotope experiments to infer metabolic fluxes through their
      carbon core pathways. Notably, 90% of all strains studied use the Entner
      Doudoroff (ED) pathway for glucose catabolism, whereas only 10% rely on the
      Embden-Meyerhof-Parnas (EMP) pathway. This result differed dramatically from the
      terrestrial model strains studied, which preferentially used the EMP pathway
      yielding high levels of ATP. Strains using the ED pathway exhibited a more robust
      resistance against the oxidative stress typically found in this environment. An
      important feature contributing to the preferential use of the ED pathway in the
      oceans could therefore be enhanced supply of NADPH through this pathway. The
      marine bacteria studied did not specifically rely on a distinct anaplerotic
      route, but the carboxylation of phosphoenolpyruvate (PEP) or pyruvate for fueling
      of the tricarboxylic acid (TCA) cycle was evenly distributed. The marine isolates
      studied belong to clades that dominate the uptake of glucose, a major carbon
      source for bacteria in seawater. Therefore, the ED pathway may play a significant
      role in the cycling of mono- and polysaccharides by bacterial communities in
      marine ecosystems. 

PMID- 25616805
TI  - Transfer of plasmid DNA to clinical coagulase-negative staphylococcal pathogens
      by using a unique bacteriophage.
AB  - Genetic manipulation of emerging bacterial pathogens, such as coagulase-negative
      staphylococci (CoNS), is a major hurdle in clinical and basic microbiological
      research. Strong genetic barriers, such as restriction modification systems or
      clustered regularly interspaced short palindromic repeats (CRISPR), usually
      interfere with available techniques for DNA transformation and therefore
      complicate manipulation of CoNS or render it impossible. Thus, current knowledge
      of pathogenicity and virulence determinants of CoNS is very limited. Here, a
      rapid, efficient, and highly reliable technique is presented to transfer plasmid
      DNA essential for genetic engineering to important CoNS pathogens from a unique
      Staphylococcus aureus strain via a specific S. aureus bacteriophage, Phi187. Even
      strains refractory to electroporation can be transduced by this technique once
      donor and recipient strains share similar Phi187 receptor properties. As a proof
      of principle, this technique was used to delete the alternative transcription
      factor sigma B (SigB) via allelic replacement in nasal and clinical
      Staphylococcus epidermidis isolates at high efficiencies. The described approach
      will allow the genetic manipulation of a wide range of CoNS pathogens and might
      inspire research activities to manipulate other important pathogens in a similar
      fashion. 

PMID- 25616806
TI  - Has cardiothoracic surgery lost its attraction?

PMID- 25616807
TI  - Re: Impact of the entry site on late outcome in acute Stanford type B aortic
      dissection.

PMID- 25616808
TI  - High rate of 5-year survival among patients with early gastric cancer undergoing
      curative endoscopic submucosal dissection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has been used to treat
      patients with early gastric cancers (EGCs), including large and ulcerative
      lesions. Few published data exist on the long-term outcomes of this treatment
      with median follow-up periods of over 5 years; we therefore aimed to assess the
      long-term outcomes of EGC patients undergoing ESD. METHODS: A total of 1,956
      consecutive patients with 2,210 EGC lesions at initial onset underwent ESD with
      curative intent at our hospital from 1999 to 2006. We performed a retrospective
      analysis of the 5-year survival of EGC patients undergoing curative ESD for
      absolute indications or for expanded indications. RESULTS: For the pathological
      curability, curative ESD for absolute indications, curative ESD for expanded
      indications of differentiated-type EGC, and curative ESD for undifferentiated
      type EGC were achieved in 781, 713, and 43 patients, respectively. The median
      follow-up period was 83.3 months. Among the 1,537 patients, there were only two
      patients with recurrence, including one who developed a regional lymph node (LN)
      metastasis and one who developed a distant LN metastasis with local recurrence
      resulting in gastric cancer-related death. Seven died from metachronous gastric
      cancers. The 5-year rates of overall survival, disease-specific survival, and
      relative survival were 92.6, 99.9, and 105.0%, respectively. CONCLUSIONS: Based
      on the high rate of 5-year survival among EGC patients undergoing curative ESD
      for absolute indications or for expanded indications in the largest patient
      series with a median follow-up period of over 5 years, ESD could be employed as a
      standard treatment for EGC lesions.

PMID- 25616809
TI  - Family synthesis research: possibilities and challenges.

PMID- 25616810
TI  - International Family Nursing Association: family nursing practice survey
      findings.

PMID- 25616811
TI  - Report from the fourth nordic Conference on Family-Focused Nursing, Odense,
      Denmark, September 24-25, 2014.

PMID- 25616813
TI  - Annular rupture during transcatheter aortic valve replacement: classification,
      pathophysiology, diagnostics, treatment approaches, and prevention.
AB  - Annular rupture is an umbrella term covering different procedural-related
      injuries that may occur in the region of the aortic root and the left ventricular
      outflow tract during transcatheter aortic valve replacement. According to the
      anatomical location of the injury, there are 4 main types: supra-annular, intra
      annular, subannular, and combined rupture. Annular rupture is a rare,
      unpredictable, and potentially fatal complication. It can be treated successfully
      if it is immediately recognized and adequately managed. The type of therapy
      depends on the location of the annular rupture and the nature of the clinical
      manifestations. Treatment approaches include conventional cardiac procedure,
      isolated pericardial drainage, and conservative therapy. This summary describes
      theoretical and practical considerations of the etiology, pathophysiology,
      classification, natural history, diagnostic and treatment strategies, and
      prevention approaches of annular rupture. 

PMID- 25616812
TI  - Decision making, central coherence and set-shifting: a comparison between Binge
      Eating Disorder, Anorexia Nervosa and Healthy Controls.
AB  - BACKGROUND: Several studies have investigated the cognitive profile in patients
      with Anorexia Nervosa (AN) and Bulimia Nervosa (BN); on the contrary few studies
      have evaluated it in patients with Binge Eating Disorder (BED). The purpose of
      this study was to compare decision making, central coherence and set-shifting
      between BED and AN patients. METHODS: A battery of neuropsychological tests
      including the Iowa Gambling Task (IGT), the Rey-Osterrieth Complex Figure Test
      (RCFT), the Wisconsin Card Sorting Test (WCST), the Trial Making Task (TMT) and
      the Hayling Sentence Completion Task (HSCT) were administered in a sample of 135
      women (45 AN, 45 BED, 45 Healthy Controls [HC]). Furthermore, Beck Depression
      Inventory (BDI) was administered to evaluate depressive symptoms. Years of
      education, age, Body Mass Index (BMI) and depression severity were considered as
      covariates in statistical analyses. RESULTS: BED and AN patients showed high
      rates of cognitive impairment compared to HC on the domains investigated;
      furthermore, the cognitive profile of BED patients was characterised by poorer
      decision making and cognitive flexibility compared to patients with AN. Cognitive
      performance was strongly associated with depressive symptoms. CONCLUSIONS: In the
      present sample, two different neurocognitive profiles emerged: a strong cognitive
      rigidity and a central coherence based on the details was predominant in patients
      with AN, while a lack of attention and difficulty in adapting to changes in a new
      situation seemed to better describe patients with BED. The knowledge of the
      different cognitive profiles of EDs patients may be important for the planning
      their psychotherapeutic intervention.

PMID- 25616814
TI  - Access site practice and procedural outcomes in relation to clinical presentation
      in 439,947 patients undergoing percutaneous coronary intervention in the United
      kingdom.
AB  - OBJECTIVES: This study sought to determine the relationships among access site
      practice, clinical presentation, and procedural outcomes in a large patient
      population. BACKGROUND: Transradial access (TRA) has been associated with
      improved patient outcomes in selected populations in randomized trials. It is
      unclear whether these outcomes are achievable in clinical practice. METHODS:
      Using the BCIS (British Cardiovascular Intervention Society) database, we
      investigated outcomes for percutaneous coronary intervention procedures
      undertaken between 2007 and 2012 according to access site practice. Patients were
      categorized as stable, non-ST-segment elevation acute coronary syndrome (NSTEACS)
      and ST-elevation acute coronary syndrome (STEACS). The impact of access site on
      30-day mortality, major adverse cardiac events, bleeding, and arterial access
      site complications was studied. RESULTS: Data from 210,260 TRA and 229,687
      transfemoral access procedures were analyzed. Following multivariate analysis,
      TRA was independently associated with a reduction in bleeding in all presenting
      syndromes (stable odds ratio [OR]: 0.24, p < 0.001; NSTEACS OR: 0.35, p < 0.001;
      STEACS OR: 0.47, p < 0.001) as well as access site complications (stable OR:
      0.21, p < 0.001; NSTEACS OR: 0.19; STEACS OR: 0.16, p < 0.001). TRA was
      associated with reduced major adverse cardiac events only in patients with
      unstable syndromes (stable OR: 1.08, p = 0.25; NSTEACS OR: 0.72, p < 0.001;
      STEACS OR: 0.70, p < 0.001). TRA was associated with improved outcomes compared
      with a transfemoral access (TFA) with a vascular closure device in a propensity
      matched cohort. CONCLUSIONS: In this large study, TRA is associated with reduced
      percutaneous coronary intervention-related complications in all patient groups
      and may reduce major adverse cardiac events and mortality in ACS patients. TRA is
      superior to transfemoral access with closure devices. Use of TRA may lead to
      important patient benefits in routine practice. TRA should be considered the
      preferred access site for percutaneous coronary intervention.

PMID- 25616799
TI  - Multilocus sequence typing of Leuconostoc gelidum subsp. gasicomitatum, a
      Psychrotrophic lactic acid bacterium causing spoilage of packaged perishable
      foods.
AB  - Leuconostoc gelidum subsp. gasicomitatum is a psychrotrophic lactic acid
      bacterium (LAB) that causes spoilage of a variety of modified-atmosphere-packaged
      (MAP) cold-stored food products. During the past 10 years, this spoilage organism
      has been increasingly reported in MAP meat and vegetable products in northern
      Europe. In the present study, the population structure within 252 L. gelidum
      subsp. gasicomitatum strains was determined based on a novel multilocus sequence
      typing (MLST) scheme employing seven housekeeping genes. These strains had been
      isolated from meat and vegetable sources over a time span of 15 years, and all 68
      previously detected pulsed-field gel electrophoresis (PFGE) genotypes were
      represented. A total of 46 sequence types (STs) were identified, with a majority
      of the strains (>60%) belonging to three major STs, which were grouped into three
      clonal complexes (CCs) and 17 singletons by Global Optimal eBURST (goeBURST). The
      results by Bayesian analysis of population structure (BAPS) mostly correlated
      with the grouping by goeBURST. Admixture analysis by BAPS indicated a very low
      level of exchange of genetic material between the subpopulations. Niche
      specificity was observed within the subpopulations: CC1 and BAPS cluster 1
      consisted mostly of strains from a variety of MAP meats, whereas vegetable
      strains grouped together with strains from MAP poultry within CC2 and BAPS
      cluster 2. The MLST scheme presented in this study provides a shareable and
      continuously growing sequence database enabling global comparison of strains
      associated with spoilage cases. This will further advance our understanding of
      the microbial ecology of this industrially important LAB. 

PMID- 25616815
TI  - An angiographic tool for risk prediction of side branch occlusion in coronary
      bifurcation intervention: the RESOLVE score system (Risk prEdiction of Side
      branch OccLusion in coronary bifurcation interVEntion).
AB  - OBJECTIVES: The purpose of this study was to establish a scoring system to
      evaluate the risk of side branch (SB) occlusion in patients undergoing coronary
      bifurcation intervention. BACKGROUND: The risk of SB occlusion is the most
      important consideration affecting the selection of an optimal intervention
      strategy. METHODS: A total of 1,545 consecutive patients undergoing percutaneous
      coronary intervention for bifurcation lesions (1,601 lesions treated with a
      single stent technique or main vessel [MV] stenting first strategy) were studied.
      A total of 1,200 lesions were used to construct the risk model and score system,
      and 401 lesions were used to validate the model. A multivariable risk score
      (RESOLVE [Risk prEdiction of Side branch OccLusion in coronary bifurcation
      interVEntion]) was constructed with incremental weights attributed to each
      component variable according to its estimated coefficients. SB occlusion after MV
      stenting was defined as any decrease in Thrombolysis in Myocardial Infarction
      flow grade or absence of flow in SB after MV stenting. RESULTS: SB occlusion
      occurred in 118 (7.37%) of 1,601 bifurcation lesions. In multivariable analyses,
      6 variables were independently associated with the risk of SB occlusion (model C
      statistic = 0.80 [95% confidence interval: 0.75 to 0.85] with good calibration).
      For the 401 lesions included in the validation cohort, the RESOLVE score had a C
      statistic of 0.77 (95% confidence interval: 0.69 to 0.86), with good calibration.
      SB occlusion rates in the validation cohort increased significantly across
      different risk groups, from 0.0% in the low-risk group, to 3.8% in the
      intermediate-risk group, and to 19.8% in the high-risk group (p < 0.001).
      CONCLUSIONS: The RESOLVE score, a novel angiographic risk stratification tool,
      can help identify patients at risk for SB occlusion during bifurcation
      intervention.

PMID- 25616816
TI  - When you ask yourself the question "should I protect the side branch?": the
      answer is "yes".

PMID- 25616817
TI  - Middle-of-the-night percutaneous coronary intervention and its association with
      percutaneous coronary intervention outcomes performed the following day: an
      analysis from the National Cardiovascular Data Registry.
AB  - OBJECTIVES: This study sought to compare in-hospital mortality and bleeding
      complications for procedures performed by sleep-deprived versus non-sleep
      deprived operators. BACKGROUND: To optimize the safety of percutaneous coronary
      intervention (PCI), it is essential to determine whether physicians performing
      emergent, middle-of-the-night procedures, and who may be sleep-deprived as a
      consequence, have equally safe outcomes when performing cases the following day.
      METHODS: We used CathPCI registry data to compare in-hospital mortality and
      bleeding complications for procedures performed by sleep-deprived versus non
      sleep-deprived operators using logistic regression with generalized estimating
      equations to account for within-operator clustering. Outcomes were risk-adjusted
      using previously validated models for in-hospital mortality and bleeding. Our
      cohort included 1,509,096 daytime PCI procedures performed by 5,014 operators
      between 7 am and midnight from July 1, 2009, through June 30, 2012. Operators
      were assumed to be acutely sleep-deprived if they began a middle-of-the-night PCI
      between midnight and 6:59 am and performed a next-day PCI between 7 am and
      midnight, and chronically sleep deprived if they had performed multiple middle-of
      the-night PCI procedures during the previous 7 days. RESULTS: Only 2.4% of all
      daytime PCI procedures were performed by operators who had performed at least 1
      middle-of-the-night PCI procedure earlier that day. In adjusted analyses, when
      comparing procedures performed by acutely sleep-deprived with non-sleep-deprived
      operators, there were no significant differences in mortality (odds ratio [OR]:
      1.02, 95% confidence interval [CI]: 0.94 to 1.12; p = 0.61) or bleeding (OR:
      1.03, 95% CI: 0.98 to 1.08; p = 0.19). However, a greater degree of chronic sleep
      deprivation was associated with a higher adjusted risk of bleeding (OR: 1.19, 95%
      CI: 1.05 to 1.34; p = 0.007). CONCLUSIONS: Daytime PCI procedures are uncommonly
      performed by sleep-deprived operators. We found no signal of increased
      complications when acutely sleep-deprived operators performed PCI but an
      increased risk of bleeding associated with procedures performed by operators with
      greater degrees of chronic sleep deprivation.

PMID- 25616818
TI  - Should interventionalist work hours be restricted after a night on call?

PMID- 25616820
TI  - Permanent pacemaker implantation following transcatheter aortic valve
      replacement: still a concern?

PMID- 25616819
TI  - Predictors and clinical outcomes of permanent pacemaker implantation after
      transcatheter aortic valve replacement: the PARTNER (Placement of AoRtic
      TraNscathetER Valves) trial and registry.
AB  - OBJECTIVES: The purpose of this study was to identify predictors and clinical
      implications of permanent pacemaker (PPM) implantation after transcatheter aortic
      valve replacement (TAVR). BACKGROUND: Cardiac conduction disturbances requiring
      PPM are a frequent complication of TAVR. However, limited data is available
      regarding this complication after TAVR with a balloon-expandable valve. METHODS:
      The study included patients without prior pacemaker who underwent TAVR in the
      PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry and
      investigated predictors and clinical effect of new PPM. RESULTS: Of 2,559 TAVR
      patients, 586 were excluded due to pre-existing PPM. A new PPM was required in
      173 of the remaining 1,973 patients (8.8%). By multivariable analysis, predictors
      of PPM included right bundle branch block (odds ratio [OR]: 7.03, 95% confidence
      interval [CI]: 4.92 to 10.06, p < 0.001), prosthesis diameter/left ventricular
      (LV) outflow tract diameter (for each 0.1 increment, OR: 1.29, 95% CI: 1.10 to
      1.51, p = 0.002), LV end-diastolic diameter (for each 1 cm, OR: 0.68, 95% CI:
      0.53 to 0.87, p = 0.003), and treatment in continued access registry (OR: 1.77,
      95% CI: 1.08 to 2.92, p = 0.025). Patients requiring PPM had a longer mean
      duration of post-procedure hospitalization (7.3 +/- 2.7 days vs. 6.2 +/- 2.8
      days, p = 0.001). At 1 year, new PPM was associated with significantly higher
      repeat hospitalization (23.9% vs. 18.2%, p = 0.05) and mortality or repeat
      hospitalization (42.0% vs. 32.6%, p = 0.007). There was no difference between
      groups in LV ejection fraction at 1 year. CONCLUSIONS: PPM was required in 8.8%
      of patients without prior PPM who underwent TAVR with a balloon-expandable valve
      in the PARTNER trial and registry. In addition to pre-existing right bundle
      branch block, the prosthesis to LV outflow tract diameter ratio and the LV end
      diastolic diameter were identified as novel predictors of PPM after TAVR. New PPM
      was associated with a longer duration of hospitalization and higher rates of
      repeat hospitalization and mortality or repeat hospitalization at 1 year. (THE
      PARTNER TRIAL: Placement of AoRtic TraNscathetER Valves Trial; NCT00530894).

PMID- 25616821
TI  - Transfemoral implantation of transcatheter heart valves after deterioration of
      mitral bioprosthesis or previous ring annuloplasty.
AB  - OBJECTIVES: This study sought to evaluate the feasibility of transfemoral
      transcatheter heart valve (THV) implantation in failed mitral bioprostheses and
      ring annuloplasties. BACKGROUND: Redo mitral surgery may be high risk or
      contraindicated due to comorbidity. THV implantation has been recently reported
      in this setting. METHODS: Transfemoral implantation of Edwards Sapien prosthesis
      was performed in 17 patients for degenerated mitral bioprosthesis or previous
      ring annuloplasty (6 bioprostheses, 11 ring annuloplasties). The procedure was
      elective for 14 patients and attempted as a rescue in 3 patients. Mean age was 61
      +/- 24 years. All patients were in New York Heart Association class >=III, and
      the surgical risk was high (EuroSCORE [European System for Cardiac Operative Risk
      Evaluation]: 37 +/- 29%, Society of Thoracic Surgeons score: 18 +/- 22%).
      RESULTS: Procedure was successful in 14 patients (82%). Two complications
      occurred during rescue procedures: 1 procedural death and 1 THV migration. One
      patient had moderate paraprosthetic regurgitation following the procedure,
      whereas residual regurgitation was trace or less in 11 patients (69%) and mild in
      4 patients (25%). Mean gradient decreased from 12 +/- 6 mm Hg to 8 +/- 3 mm Hg.
      During a mean follow-up of 22 months, 4 patients died, 3 from cardiac cause. The
      18-month survival was 68 +/- 14% in the overall population and 78 +/- 14% for
      patients with elective procedure. One patient underwent mitral valve replacement
      due to periprosthetic mitral regurgitation. At last follow-up, 12 patients were
      in New York Heart Association class <=II (75%) and 4 in class III (25%).
      CONCLUSIONS: This single-center series suggests that transfemoral THV
      implantation for deterioration of mitral bioprosthesis or surgical repair is
      feasible in selected patients and improves early hemodynamic and midterm
      functional status.

PMID- 25616823
TI  - The THUNDER trial results: clearing the way or ushering the storm?

PMID- 25616822
TI  - Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year
      follow-up of the THUNDER trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the 5-year follow-up (FU)
      data of the THUNDER (Local Taxan With Short Time Contact for Reduction of
      Restenosis in Distal Arteries). BACKGROUND: The THUNDER trial was the first study
      to investigate the treatment of femoropopliteal arteries with a paclitaxel-coated
      balloon (PCB). METHODS: In 154 patients, femoropopliteal arteries were treated
      with PCB, with angioplasty with paclitaxel in contrast medium, or no paclitaxel
      (control). The primary endpoint was 6-month late lumen loss (LLL). Secondary
      endpoints included freedom from target lesion revascularization (TLR), binary
      restenosis rate, and amputation. The 5-year FU compares outcomes in patients
      treated with PCB and control subjects. Additionally, LLL at 6 months and TLR up
      to 5-year FU were analyzed in terms of sex and lesion length. RESULTS: Over the 5
      year period, the cumulative number of patients with TLR remained significantly
      lower in the PCB group (21%) than in the control group (56%, p = 0.0005). In the
      small group of patients with angiographic and duplex sonographic follow-up, PCB
      was associated with a lower rate of binary restenosis (17% vs. 54%; p = 0.04). No
      signs of aneurysm formation or constrictive fibrosis were detected. Whereas LLL
      at 6-month FU did not differ between men and women in the PCB group, the TLR rate
      was lower in men than in women at 5-year FU. A benefit of PCB treatment in terms
      of LLL and TLR was seen independent of lesion length. CONCLUSIONS: The reduced
      TLR rate following PCB treatment was maintained over the 5-year FU period. No
      signs of drug-related local vessel abnormalities were detected. (Thunder Trial
      Local Taxan With Short Time Contact for Reduction of Restenosis in Distal
      Arteries [THUNDER]; NCT00156624).

PMID- 25616824
TI  - MitraClip implantation in a previous surgical mitral valve edge-to-edge repair.

PMID- 25616825
TI  - Giant coronary aneurysm diagnosed as incidental mediastinal mass.

PMID- 25616826
TI  - Side branch occlusion after bioresorbable vascular scaffold implantation: lessons
      from optimal coherence tomography.

PMID- 25616827
TI  - Anatomic guided crossing of a stenotic aortic valve under fluoroscopy: "right
      cusp rule, part III".

PMID- 25616828
TI  - Calcified nodule mimicking red thrombus on optical coherence tomography.

PMID- 25616829
TI  - Reply: calcified nodule mimicking red thrombus on optical coherence tomography.

PMID- 25616830
TI  - The optimal cutoff value for left main minimal lumen area of 4.5 mm(2): a word of
      caution.

PMID- 25616831
TI  - Reply: the optimal cutoff value for left main minimal lumen area of 4.5 mm(2): a
      word of caution.

PMID- 25616832
TI  - Intracardiac echocardiographic imaging of the left atrial appendage and detection
      of a peridevice leak after device occlusion.

PMID- 25616833
TI  - Reply: intracardiac echocardiographic imaging of the left atrial appendage and
      detection of a peridevice leak after device occlusion.

PMID- 25616834
TI  - What is it like to be an editor?

PMID- 25616836
TI  - Occlusion of balloon-expandable stent in the common iliac artery due to
      compression by a spinal spur.

PMID- 25616835
TI  - Impingement of left main ostium after device occlusion of paravalvular leak post
      transcatheter aortic valve replacement.

PMID- 25616837
TI  - Knowledge is Power! Increased Provider Knowledge Scores Regarding Pre-exposure
      Prophylaxis (PrEP) are Associated with Higher Rates of PrEP Prescription and
      Future Intent to Prescribe PrEP.
AB  - The FDA approval of emtricitabine/tenofovir disoproxil fumarate for pre-exposure
      prophylaxis (PrEP) in 2012 has raised questions about the delivery of PrEP in a
      real-world setting. iPad-based questionnaires were given to providers at
      conferences in California and New York to assess knowledge, experience and
      attitudes regarding PrEP in HIV and non-HIV providers. HIV provider status was
      defined either by self-identification or by having greater than 5 years of HIV
      care experience. Knowledge scores were the sum of correct answers from five PrEP
      knowledge questions. Univariate analyses used t-test to compare knowledge scores
      and Fisher's exact test for past or future PrEP prescription between HIV and non
      HIV providers. Multivariable linear or logistic regression models were used to
      assess factors associated with the outcomes. Of 233 respondents, the mean age was
      40 years, 59 % were White, 59 % were physicians and 52 % were HIV providers. In
      univariate analysis, mean PrEP knowledge scores (max 5) were significantly higher
      for HIV providers (2.8 versus 2.2; p < 0.001), age > 41 (mean 2.8 versus 2.3; p =
      0.004), White race (2.7 versus 2.2; p = 0.026) and participants in the New York
      region (3.0 versus 2.3; p < 0.001). In a multivariable model of knowledge scores,
      all but age remained significant. Among 201 potential prescribers, the rate of
      prior PrEP prescription was higher among HIV providers than non-HIV providers (34
      versus 9 %; p < 0.001) and by knowledge score, but the association with provider
      status was no longer significant in multivariable analysis that controlled for
      knowledge. Intent to prescribe PrEP in the future was high for all provider types
      (64 %) and was associated with knowledge scores in multivariable analysis. The
      most common concerns about PrEP (>40 % of providers) were drug toxicities,
      development of resistance and patient adherence to follow-up; 32 % identified
      risk compensation as a concern. HIV providers had significantly greater PrEP
      knowledge than non-HIV providers, but differences by provider type in past PrEP
      prescription were largely dependent on knowledge. Future PrEP prescription was
      also associated with knowledge, though all providers expressed greater future
      use. Education of potential PrEP providers will be a key component of successful
      PrEP implementation.

PMID- 25616838
TI  - A Randomized Trial to Evaluate the Efficacy of a Web-Based HIV Behavioral
      Intervention for High-Risk African American Women.
AB  - The aim of this study was to develop and test a cost-effective, scalable HIV
      behavioral intervention for African American women. Eighty-three African American
      women were recruited from a community health center and randomly assigned to
      either the web-based Safe Sistah program or to a delayed HIV education control
      condition. The primary outcome was self-reported condom use. Secondary measures
      assessed other aspects of the gender-focused training included in Safe Sistah.
      Participants completed self-report assessments prior to randomization, 1- and 4
      months after their program experience. Across the entire study period, women in
      the experimental condition significantly increased their condom use relative to
      controls (F = 5.126, p = 0.027). Significant effects were also found for sexual
      communication, sex refusal, condom use after alcohol consumption, and HIV
      prevention knowledge. These findings indicate that this web-based program could
      be an important component in reducing the HIV disparities among African American
      women.

PMID- 25616839
TI  - A new metabolic mechanism for absence of pain in patients with silent myocardial
      ischemia.
AB  - BACKGROUND AND AIMS: We undertook this study to detect if there is a relationship
      between lactate production in the myocardium and the presence or absence of chest
      pain in patients with coronary artery disease (CAD). METHODS: Forty six patients
      with significant CAD including left anterior descending artery underwent
      echocardiography study, coronary angiography and pacing-induced ischemia. Serum
      lactate levels were determined in four blood samples, from mid-LV cavity and from
      coronary sinus before and after pacing-induced ischemia. Twenty eight patients
      comprised angina group and 18 patients comprised silent myocardial ischemia (SMI)
      group during pacing-induced ischemia. RESULTS: Eighteen patients (64.3%) of
      angina group had lactate production during ischemia. Eighteen patients of SMI
      group (100%) had diminished lactate extraction, and none had lactate production.
      CONCLUSION: The novel finding of this study is that the major difference in
      metabolism during SMI and angina pectoris is in the state of lactate production,
      which is absent during SMI and present during angina. We assume that lactate is
      the stimulus of cardiac ischemic pain and when its level increases, it stimulates
      pain receptors leading to chest pain.

PMID- 25616840
TI  - Comparison of Lentiviral Packaging Mixes and Producer Cell Lines for RNAi
      Applications.
AB  - Lentiviral transduction is a highly efficient DNA delivery method for RNA
      interference applications. However, obtaining high lentiviral titers of shRNA and
      miRNA encoding vectors is challenging, since shRNA and miRNA cassettes have been
      shown to reduce lentiviral titers. In this study, we compare four commercially
      available packaging mixes and two producer cell lines in order to optimize
      lentiviral production for gene silencing experiments. Lentiviral vectors encoding
      a miRNA sequence and emerald green fluorescence protein were co-transfected with
      ViraPowerTM, Lenti-XTM HTX, MISSION((r)) Lentiviral or Trans-LentiviralTM
      packaging mix in HEK-293T or 293FT cells. After transducing HeLa cells with virus
      containing supernatant, lentiviral titers were determined by flow cytomerty. In
      both cell lines, the highest lentiviral titer was obtained with MISSION((r))
      Lentiviral packaging mix, followed by ViraPowerTM, Lenti-XTM HTX, and Trans
      LentiviralTM. On average, HEK-293T cells produced 6.2-fold higher lentiviral
      titers than 293FT cells (p < 0.001). With the combination of MISSION((r))
      Lentiviral packaging mix and HEK-293T cells, an up to 48.5-fold higher lentiviral
      titer was reached compared to other packaging mixes and producer cell lines. The
      optimized selection of packaging mix and cell line described in this work should
      facilitate the production of high-titer lentiviruses for gene silencing
      experiments.

PMID- 25616841
TI  - Nursing education: preparing for the inevitability of disasters and emergencies.

PMID- 25616842
TI  - Hepatitis B virus and hepatitis C virus infection among HIV-1-infected injection
      drug users in Dali, China: prevalence and infection status in a cross-sectional
      study.
AB  - To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infection and to investigate their mutual influences on infection status among
      human immunodeficiency virus type 1 (HIV-1)-seropositive injection drug users
      (IDUs). A cross-sectional study was conducted among HIV infected IDUs in Dali,
      China. The participants were tested for serological markers of HBV and HCV
      infection, alanine transaminase (ALT) activity and CD4(+) T cell count. HCV
      genotype was determined by sequencing. Of 529 patients, 498 (94.1 %) HIV infected
      IDUs agreed to participate. The overall prevalence of HCV infection (anti-HCV
      antibody positive) and spontaneous HCV clearance were 90.8 % (452/498) and 21.5 %
      (97/452), respectively. Of 411 subjects who had not received HBV vaccine, 296
      (72.0 %) were positive for antibody against HBV core antigen (HBcAb), while 274
      (66.7 %) were positive for both HCV antibody and HBcAb. HBV antigens were
      detected in 52 of the HBV-infected subjects (17.6 %). HCV clearance was
      associated with HBV antigenemia (p = 0.0002) and higher CD4(+) T cell count (p =
      0.0294). Resolved HBV infection was associated with HCV genotype 3 (p = 0.0365).
      HBV and HCV infection are highly prevalent and mutually influence infection
      status in HIV-1 infected IDUs in Dali, China.

PMID- 25616843
TI  - Recombinant influenza A virus hemagglutinin HA2 subunit protects mice against
      influenza A(H7N9) virus infection.
AB  - A novel avian influenza A(H7N9) virus has emerged to infect humans in eastern
      China since 2013. An effective vaccine is needed because of the high mortality
      despite antiviral treatment and intensive care. We sought to develop an effective
      vaccine for A(H7N9) virus. The HA2 subunit was chosen as the vaccine antigen
      because it is highly conserved among the human A(H7N9) virus strains. Moreover,
      in silico analysis predicted two immunogenic regions within the HA2 subunit that
      may contain potential human B-cell epitopes. The HA2 fragment was readily
      expressed in Escherichia coli. In BALB/c mice, intraperitoneal immunization with
      two doses of HA2 with imiquimod (2-dose-imiquimod) elicited the highest geometric
      mean titer (GMT) of anti-HA2 IgG (12699), which was greater than that of two
      doses of HA2 without imiquimod (2-dose-no-adjuvant) (6350), one dose of HA2 with
      imiquimod (1-dose-imiquimod) (2000) and one dose of HA2 without imiquimod (1-dose
      no-adjuvant) (794). The titer of anti-HA2 IgG was significantly higher in the 1
      dose-imiquimod group than the 1-dose-no-adjuvant group. Although both
      hemagglutination inhibition titers and microneutralization titers were below 10,
      serum from immunized mice showed neutralizing activity in a fluorescent focus
      microneutralization assay. In a viral challenge experiment, the 2-dose-imiquimod
      group had the best survival rate (100 %), followed by the 2-dose-no-adjuvant
      group (90 %), the 1-dose-imiquimod group (70 %) and the 1-dose-no-adjuvant group
      (40 %). The 2-dose-imiquimod group also had significantly lower mean pulmonary
      viral loads than the 1-dose-imiquimod, 1-dose-no-adjuvant and non-immunized
      groups. This recombinant A(H7N9)-HA2 vaccine should be investigated as a
      complement to egg- or cell-based live attenuated or subunit influenza vaccines.

PMID- 25616844
TI  - The sero-prevalence of anti-adenovirus 5 neutralizing antibodies is independent
      of a chronic hepatitis B carrier state in China.
AB  - We investigated the prevalence of neutralizing antibodies (NA) to human
      Adenovirus (Ad) 5 both in healthy subjects (HS) and Chronic Hepatitis B (CHB)
      patients in Shanghai. Detection of anti-Ad5 NA (percentage of detection and
      titers) was similar between HS and CHB patients. A high percentage of subjects
      harbored no detectable antibodies (32.2 %) while proportion of subjects
      displaying very high antibody titers was low (4 %). Neither demographic factors
      (gender, age, health) nor AST/ALT or HBV circulating DNA titers affected
      detection of Ad5-specific NA. These observations pave the ground for development
      of Ad5-based immunotherapeutics aiming at treating CHB patients in China.

PMID- 25616845
TI  - Comparison of biological characteristics of H9N2 avian influenza viruses isolated
      from different hosts.
AB  - The pathogenicity and transmissibility of H9N2 influenza viruses has been widely
      investigated; however, few studies comparing the biological characteristics of
      H9N2 viruses isolated from different hosts have been performed. In this study,
      eight H9N2 viruses, isolated from chickens (Ck/F98, Ck/AH and Ck/TX), pigeons
      (Pg/XZ), quail/(Ql/A39), ducks (Dk/Y33) and swine (Sw/YZ and Sw/TZ) were
      selected, and their biological characteristics were determined. The results
      showed that all H9N2 viruses maintained a preference for both the avian- and
      human-type receptors, except for Sw/TZ, which had exclusive preference for the
      human-type receptor. The viruses replicated well in DF-1 and MDCK cells, whereas
      only three isolates, Ck/F98, Ck/TX and Sw/TZ, could replicate in A549 cells and
      also replicated in mouse lungs, resulting in body weight loss in mice. All H9N2
      viruses were nonpathogenic to chickens and were detected in the trachea and lung
      tissues. The viruses were shed primarily by the oropharynx and were transmitted
      efficiently to naive contact chickens. Our findings suggest that all H9N2 viruses
      from different hosts exhibit efficient replication and contact-transmission among
      chickens, and chickens serve as a good reservoir for the persistence and
      interspecies transmission of H9N2 influenza viruses. 

PMID- 25616846
TI  - Comparison of miniplates and biodegradable plates in reconstruction of the
      mandible with a fibular free flap.
AB  - Miniplates and reconstruction plates are usually used to fix a fibular free flap,
      the gold standard in reconstruction of large segmental mandibular defects. Though
      biodegradable plates are used in orthognathic operations and repair of fractures
      nowadays, we know of no studies of the use of biodegradable plates in the
      reconstruction of segmental mandibular defects including a fibular free flap. We
      retrospectively reviewed 47 patients who had reconstruction of segmental
      mandibular defects with fibular free flaps during the past 10 years, and recorded
      clinical data and morbidity. We compared patients who had reconstruction of such
      defects with fibular free flaps and miniplates (n=26) with those in whom
      biodegradable plates had been used (n=21). There was no significant difference
      between miniplates and biodegradable plates with regard to overall complications
      (p=0.45) and failure of flaps (p=0.59). After confounding factors had been
      adjusted for with Cox's proportional hazards regression, there was no significant
      difference in the proportion of patients who developed a complication between the
      two groups (p=0.4). The type of plate does not seem to affect overall morbidity
      in reconstruction of the mandible with a fibular free flap.

PMID- 25616847
TI  - Paramagnetic relaxation enhancement solid-state NMR studies of heterogeneous
      catalytic reaction over HY zeolite using natural abundance reactant.
AB  - Paramagnetic relaxation enhancement solid-state NMR (PRE ssNMR) technique was
      used to investigate catalytic reaction over zeolite HY. After introducing
      paramagnetic Cu(II) ions into the zeolite, the enhancement of longitudinal
      relaxation rates of nearby nuclei, i.e.(29)Si of the framework and (13)C of the
      absorbents, was measured. It was demonstrated that the PRE ssNMR technique
      facilitated the fast acquisition of NMR signals to monitor the heterogeneous
      catalytic reaction (such as acetone to hydrocarbon) using natural abundance
      reactants. 

PMID- 25616848
TI  - A new three-dimensional measurement in evaluating the cranial asymmetry caused by
      craniosynostosis.
AB  - PURPOSE: To present a modified cranial vault asymmetry index, evaluate it by
      measuring the asymmetry of the skull shape with craniosynostosis and by assessing
      the surgical outcome quantitatively, compare it with traditional cranial vault
      asymmetry index (CVAI) and discuss its advantages and shortcomings. METHODS:
      Based on the traditional CVAI, anterior cranial vault asymmetry index (ACVAI) and
      posterior cranial vault asymmetry index (PCVAI) were proposed to evaluate
      surgical outcomes. We measured CVAI, ACVAI and PCVAI on the reconstructed three
      dimensional computed tomography images to analyze the degree of the malformation
      and assess the surgical outcomes. The new method was compared with the
      traditional one, and statistical analysis was performed. RESULTS: Using Wilcoxon
      Rank Sum Test, preoperative ACVAI compared to postoperative one is statistically
      significant (p = 0.018), whereas, the p value for CVAI is 0.128 > 0.05.
      CONCLUSIONS: The ACVAI and PCVAI as modified can better describe the degree of
      cranial vault asymmetry compared with CVAI. It is also a more reliable index to
      assess the surgical outcomes quantitatively.

PMID- 25616849
TI  - Branch of the canalis sinuosus: a rare anatomical variation--a case report.
AB  - The canalis sinuosus (CS) is a neurovascular canal, a branch of the infraorbital
      canal through which the anterior superior alveolar nerve passes. There are no
      studies or case reports of anatomical variations related to this canal. A rare
      case of anatomical variation in the CS is reported that was detected by cone beam
      computed tomography done in a 47-year-old female as a pre-operative workup before
      dental implants. In this case, in the region slightly medial to tooth 23, a wide
      accessory branch from the CS was observed, running an intraosseous course in the
      inferior and posterior direction up to a foramen located in the hard palate,
      slightly medial in relation to tooth 23. The location of this branching, as well
      as its neurovascular component, is important for dental implant planning because
      of its proximity to the upper teeth. Identification of neurovascular bundles is
      fundamental to avoid complications for the patient. 

PMID- 25616850
TI  - Extra middle turbinate lamellas: a suggested new classification.
AB  - PURPOSE: Proper knowledge of sinonasal configurations and anatomical structural
      variations is essential to perform safe endoscopic sinus surgery. Although common
      middle turbinate variations have been well described in literature, rare
      variations have not. The aims of this study are to revise the nomenclature of
      extra middle turbinate lamellas variations and suggest an easy classification
      system of these lamellas. METHOD: A retrospective charts and medical records
      review was performed for consecutive cases that were diagnosed with extra lamella
      middle turbinate based on endoscopic and stander three-dimensional reconstruction
      computer tomography scan at a tertiary academic center. After extensive
      literature review, these lamellas were classified into four types depending on
      the presence or absence of uncinate process and their morphological
      configuration. RESULT: Twenty-two subjects (mean age 35 years; 8 men and 14
      women) were identified who had thirty extra middle turbinate lamellas. Nasal
      obstruction and discharge were the most common presenting symptoms. Accessory
      middle turbinate was the most common extra lamella been observed and bifid
      inferior turbinate was the least common. Ten patients (45 %) had an accompanied
      middle turbinate anatomical variations, 9 (41 %) had nasal septum deviation, 11
      (50 %) had associated maxillary or ethmoid sinusitis and 5 (23 %) had hypoplastic
      maxillary sinus. CONCLUSION: Extra middle turbinate lamella is a rare type of
      middle turbinate anatomical variation that can be diagnosed by careful endoscopic
      examination and a precise computer tomography scan review. These lamellas may
      have a significant association with mucosa pathologies and are commonly seen with
      other common middle turbinate variations. Correct description and the use of
      common terminology can help to further evaluate the incidence of lamellas, their
      pathophysiological role, and to avoid any intraoperative landmark confusion.

PMID- 25616851
TI  - Night shift work and lung cancer risk among female textile workers in Shanghai,
      China.
AB  - In 2007, the International Agency for Research on Cancer classified shift work
      that involves circadian disruption as a probable human carcinogen. Suppression of
      the anti-neoplastic hormone, melatonin, is a presumed mechanism of action. We
      conducted a case-cohort study nested within a cohort of 267,400 female textile
      workers in Shanghai, China. Newly diagnosed lung cancer cases (n = 1451)
      identified during the study period (1989-2006) were compared with an age
      stratified subcohort (n = 3040). Adjusting for age, smoking, parity, and
      endotoxin exposure, relative risks [hazard ratios (HRs)] were estimated by Cox
      regression modeling to assess associations with cumulative years and nights of
      rotating shift work. Results did not consistently reveal any increased risk of
      lung cancer among rotating shift work or statistically significant trends for
      both cumulative years (HR 0.82, 95% CI 0.66 to 1.02; P(trend) = 0.294) and nights
      (HR 0.81, 95% CI 0.65 to 1.00; P(trend) = 0.415). Further analyses imposing 10-
      and 20-year lag times for disease latency also revealed similar results. Contrary
      to the initial hypothesis, rotating nighttime shift work appears to be associated
      with a relatively reduced lung cancer risk although the magnitude of the effect
      was modest and not statistically significant.

PMID- 25616853
TI  - Examining the Relationship Between Flexible Resources and Health Information
      Channel Selection.
AB  - This study examines how variations in flexible resources influence where
      individuals begin their search for health information. Access to flexible
      resources such as money, power, and knowledge can alter the accessibility of
      channels for health information, such as doctors, the Internet, and print media.
      Using the HINTS 3 sample, whether information channel utilization is predicted by
      the same factors in two groups with distinct levels of access to flexible
      resources, as approximated by high and low levels of education, is investigated.
      Differences in access to flexible resources are hypothesized to produce
      variations in channel utilization in bivariate analyses, as well as changes in
      coefficient strength and statistical significance in multivariate models.
      Multinomial logit models were used to assess how a number of variables influence
      the probability of using a specific information channel first in either flexible
      resource group. Results suggest that individuals with higher levels of education,
      a proxy for flexible resources, are more likely to report seeking information
      from the Internet first, which is consistent with research on the digital divide.
      It appears that diminished access to flexible resources is also associated with
      heightened utilization of offline channels, including doctors. A handful of
      differences in predictors were found between the low and high flexible resource
      groups when multivariate models were compared. Future research should take into
      account the distinctions between different offline channels while also seeking to
      further understand how social inequality relates to the utilization of different
      channels and corresponding health outcomes. 

PMID- 25616852
TI  - Quantifying the acute changes in glucose with exercise in type 1 diabetes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The acute impact of different types of physical activity on glycemic
      control in type 1 diabetes has not been well quantified. OBJECTIVES: Our
      objective was to estimate the rate of change (RoC) in glucose concentration
      induced acutely during the performance of structured exercise and at recovery in
      subjects with type 1 diabetes. METHODS: We searched for original articles in the
      PubMed, MEDLINE, Scopus, and Cochrane databases. Search terms included type 1
      diabetes, blood glucose, physical activity, and exercise. Eligible studies
      (randomized controlled trials and non-randomized experiments) encompassed
      controlled physical activity sessions (continuous moderate [CONT], intermittent
      high intensity [IHE], resistance [RESIST], and/or a resting reference [REST]) and
      reported excursions in glucose concentration during exercise and after its
      cessation. Data were extracted by graph digitization to compute two RoC measures
      from population profiles: RoCE during exercise and RoCR in recovery. RESULTS: Ten
      eligible studies were found from 540 publications. Meta-analyses of exercise
      modalities versus rest yielded the following: RoCE -4.43 mmol/L h(-1) (p <
      0.00001, 95% confidence interval [CI] -6.06 to -2.79) and RoCR +0.70 mmol/L h(-1)
      (p = 0.46, 95% CI -1.14 to +2.54) for CONT vs. REST; RoCE -5.25 mmol/L.h(-1) (p <
      0.00001, 95 % CI -7.02 to -3.48) and RoCR +0.72 mmol/L h(-1) (p = 0.71, 95% CI 
      3.10 to +4.54) for IHE vs. REST; RoCE -2.61 mmol/L h(-1) (p = 0.30, 95% CI -7.55
      to +2.34) and RoCR -0.02 mmol/L h(-1) (p = 1.00, 95% CI -7.58 to +7.53) for
      RESIST vs. REST. CONCLUSIONS: Novel RoC magnitudes RoCE, RoCR reflected rapid
      decays of glycemia during CONT exercise and gradual recoveries immediately
      afterwards. RESIST showed more constrained decays, whereas discrepancies were
      found for IHE.

PMID- 25616854
TI  - IOM report calls for culture of data sharing.

PMID- 25616856
TI  - Second-line option for colorectal cancer.

PMID- 25616857
TI  - Free-breathing T2* mapping using respiratory motion corrected averaging.
AB  - BACKGROUND: Pixel-wise T2* maps based on breath-held segmented image acquisition
      are prone to ghost artifacts in instances of poor breath-holding or cardiac
      arrhythmia. Single shot imaging is inherently immune to ghost type artifacts. We
      propose a free-breathing method based on respiratory motion corrected single shot
      imaging with averaging to improve the signal to noise ratio. METHODS: Images were
      acquired using a multi-echo gradient recalled echo sequence and T2* maps were
      calculated at each pixel by exponential fitting. For 40 subjects (2 cohorts), two
      acquisition protocols were compared: (1) a breath-held, segmented acquisition,
      and (2) a free-breathing, single-shot multiple repetition respiratory motion
      corrected average. T2* measurements in the interventricular septum and liver were
      compared for the 2-methods in all studies with diagnostic image quality. RESULTS:
      In cohort 1 (N = 28) with age 51.4 +/- 17.6 (m +/- SD) including 1 subject with
      severe myocardial iron overload, there were 8 non-diagnostic breath-held studies
      due to poor image quality resulting from ghost artifacts caused by respiratory
      motion or arrhythmias. In cohort 2 (N = 12) with age 30.9 +/- 7.5 (m +/- SD),
      including 7 subjects with severe myocardial iron overload and 4 subjects with
      mild iron overload, a single subject was unable to breath-hold. Free-breathing
      motion corrected T2* maps were of diagnostic quality in all 40 subjects. T2*
      measurements were in excellent agreement (In cohort #1, T2*FB = 0.95 x T2*BH +
      0.41, r2 = 0.93, N = 39 measurements, and in cohort #2, T2*FB = 0.98 x T2*BH +
      0.05, r2 > 0.99, N = 22 measurements). CONCLUSIONS: A free-breathing approach to
      T2* mapping is demonstrated to produce consistently good quality maps in the
      presence of respiratory motion and arrhythmias.

PMID- 25616858
TI  - Which motion segments are required to sufficiently characterize the kinematic
      behavior of the trunk?
AB  - Various kinematic definitions of the thoracic spine have been employed in past
      work. However, the segments necessary to sufficiently characterize the thoracic
      spine during trunk movements in all three planes of motion have not yet been
      identified. This study aimed to determine the minimum number of segments
      necessary to adequately characterize the kinematics of the thoracic spine. Thirty
      individuals, asymptomatic for back pain, performed ten trials of maximum trunk
      flexion, lateral bend, and axial twist; thoracic flexion, lateral bend, and axial
      twist; and slumped standing. Marker clusters were applied over the C(7), T(3),
      T(6), T(9), T(12), and L(5) vertebrae. Three-dimensional angles of each cluster
      were calculated, and cross-correlation (R(xy(time))) and correlation (R(xy(max)))
      analyses were employed to assess the relationships in the motion patterns and
      maximum angles of adjacent clusters, respectively. The motion patterns and
      maximum angles of adjacent clusters were very strongly (R(xy(time)) > 0.90 for 26
      of 35 pairings) and strongly (R(xy(max)) > 0.80 for 25 of 35 pairings)
      correlated, respectively. A four-cluster set (C(7), T(6), T(12), and L(5))
      represented thoracic movement for six of the seven movement tasks tested. These
      results provide insight into thoracic movement coordination, with implications
      for predictive spinal modeling and clinical assessment practices.

PMID- 25616859
TI  - Electron transport kinetics in the diazotrophic cyanobacterium Trichodesmium spp.
      grown across a range of light levels.
AB  - The diazotrophic cyanobacterium Trichodesmium is a major contributor to marine
      nitrogen fixation. We analyzed how light acclimation influences the
      photophysiological performance of Trichodesmium IMS101 during exponential growth
      in semi-continuous nitrogen fixing cultures under light levels of 70, 150, 250,
      and 400 MUmol photons m(-2) s(-1), across diel cycles. There were close
      correlations between growth rate, trichome length, particulate organic carbon and
      nitrogen assimilation, and cellular absorbance, which all peaked at 150 MUmol
      photons m(-2) s(-1). Growth rate was light saturated by about 100 MUmol photons
      m(-2) s(-1) and was photoinhibited above 150 MUmol photons m(-2) s(-1). In
      contrast, the light level (I k) to saturate PSII electron transport (e (-) PSII(
      1) s(-1)) was much higher, in the range of 450-550 MUmol photons m(-2) s(-1), and
      increased with growth light. Growth rate correlates with the absorption cross
      section as well as with absorbed photons per cell, but not to electron transport
      per PSII; this disparity suggests that numbers of PSII in a cell, along with the
      energy allocation between two photosystems and the state transition mechanism
      underlie the changes in growth rates. The rate of state transitions after a
      transfer to darkness increased with growth light, indicating faster respiratory
      input into the intersystem electron transport chain.

PMID- 25616861
TI  - Management of a child with nutritional rickets, multiple cavities, enamel
      hypoplasia, and reactive attachment disorder.

PMID- 25616862
TI  - Scan path optimization with/without clustering for active beam delivery in
      charged particle therapy.
AB  - PURPOSE: To compare different algorithms to optimize the scanning path in charged
      particle therapy with quasidiscrete scanning. We implemented a Hybrid Genetic
      Algorithm with Heuristics (HyGA) and combined it with clustering techniques. The
      performance was compared to Simulated Annealing (SA) and to commercially
      available treatment planning system (TPS). METHODS: Performance and clinical
      implications were assessed using data from 10 patients treated at CNAO (Centro
      Nazionale di Adroterapia Oncologica). Clinical treatments are performed relying
      on beam deflection, avoiding irradiation for transitions between adjacent spots
      larger than 2 cm. A clustering method was implemented with HyGA (HyGA_Cl), which
      assumes beam deflection during transition between clusters. Clinical performance
      was determined as the total number of particles delivered during spot transitions
      and the number of particles wasted due to beam deflection. Results were compared
      to scan paths obtained with CNAO TPS. RESULTS: SA and HyGA produced on average
      shorter paths compared to the currently available TPS. This did not result in a
      reduction of transit particles, due to the concomitant effect of beam deflection
      out of the extraction line. HyGA_Cl achieved 2% average reduction in transit
      particles when compared to CNAO TPS. As a drawback, wasted particles increased,
      due to more frequent use of beam deflection. Both the SA and HyGA algorithms
      reduced the number of wasted particles. CONCLUSION: SA and HyGA proved to be the
      most cost-effective methods in reducing wasted particles, with benefits in terms
      of shorter scan paths. A decrease in transit particles delivered with beam
      deflection can be achieved using HyGA_Cl.

PMID- 25616863
TI  - Anti-inflammatory deficiencies in neutrophilic asthma: reduced galectin-3 and IL
      1RA/IL-1beta.
AB  - BACKGROUND: Galectin-3 (gal-3), a member of the beta-galactoside-binding animal
      lectins, is involved in the recruitment, activation and removal of neutrophils.
      Neutrophilic asthma is characterized by a persistent elevation of airway
      neutrophils and impaired efferocytosis. We hypothesized that sputum gal-3 would
      be reduced in neutrophilic asthma and the expression of gal-3 would be associated
      with other markers of neutrophilic inflammation. METHODS: Adults with asthma (n =
      80) underwent a sputum induction following clinical assessment and blood
      collection. Sputum was dispersed for a differential cell count and ELISA
      assessment of gal-3, gal-3 binding protein (BP), interleukin (IL)-1beta, IL-1
      receptor antagonist (RA), IL-8 and IL-6. Gal-3 and gal-3BP immunoreactivity were
      assessed in mixed sputum cells. RESULTS: Sputum gal-3 (median, (q1,q3)) was
      significantly reduced in neutrophilic asthma (183 ng/mL (91,287)) compared with
      eosinophilic (293 ng/mL (188,471), p = 0.021) and paucigranulocytic asthma (399
      ng/mL (213,514), p = 0.004). The gal-3/gal-3BP ratio and IL-1RA/IL-1beta ratio
      were significantly reduced, while gal-3BP and IL-1beta were significantly
      elevated in neutrophilic asthma compared with eosinophilic and paucigranulocytic
      asthma. CONCLUSION: Patients with neutrophilic asthma have impairment in anti
      inflammatory ratio of gal-3/gal-3BP and IL-1RA/IL-1beta which provides a further
      framework for exploration into pathologic mechanisms of asthma phenotypes.

PMID- 25616864
TI  - Simple and Multivariate Relationships Between Spiritual Intelligence with General
      Health and Happiness.
AB  - The present study examined simple and multivariate relationships of spiritual
      intelligence with general health and happiness. The employed method was
      descriptive and correlational. King's Spiritual Quotient scales, GHQ-28 and
      Oxford Happiness Inventory, are filled out by a sample consisted of 384 students,
      which were selected using stratified random sampling from the students of Shahid
      Bahonar University of Kerman. Data are subjected to descriptive and inferential
      statistics including correlations and multivariate regressions. Bivariate
      correlations support positive and significant predictive value of spiritual
      intelligence toward general health and happiness. Further analysis showed that
      among the Spiritual Intelligence' subscales, Existential Critical Thinking
      Predicted General Health and Happiness, reversely. In addition, happiness was
      positively predicted by generation of personal meaning and transcendental
      awareness. The findings are discussed in line with the previous studies and the
      relevant theoretical background. 

PMID- 25616865
TI  - Deep proteomics of mouse skeletal muscle enables quantitation of protein
      isoforms, metabolic pathways, and transcription factors.
AB  - Skeletal muscle constitutes 40% of individual body mass and plays vital roles in
      locomotion and whole-body metabolism. Proteomics of skeletal muscle is
      challenging because of highly abundant contractile proteins that interfere with
      detection of regulatory proteins. Using a state-of-the art MS workflow and a
      strategy to map identifications from the C2C12 cell line model to tissues, we
      identified a total of 10,218 proteins, including skeletal muscle specific
      transcription factors like myod1 and myogenin and circadian clock proteins. We
      obtain absolute abundances for proteins expressed in a muscle cell line and
      skeletal muscle, which should serve as a valuable resource. Quantitation of
      protein isoforms of glucose uptake signaling pathways and in glucose and lipid
      metabolic pathways provides a detailed metabolic map of the cell line compared
      with tissue. This revealed unexpectedly complex regulation of AMP-activated
      protein kinase and insulin signaling in muscle tissue at the level of enzyme
      isoforms. 

PMID- 25616867
TI  - Proteomics analyses for the global proteins in the brain tissues of different
      human prion diseases.
AB  - Proteomics changes of brain tissues have been described in different
      neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.
      However, the brain proteomics of human prion disease remains less understood. In
      the study, the proteomics patterns of cortex and cerebellum of brain tissues of
      sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic
      CJD were analyzed with isobaric tags for relative and absolute quantitation
      combined with multidimensional liquid chromatography and MS analysis, with the
      brains from three normal individuals as controls. Global protein profiling,
      significant pathway, and functional categories were analyzed. In total, 2287
      proteins were identified with quantitative information both in cortex and
      cerebellum regions. Cerebellum tissues appeared to contain more up- and down
      regulated proteins (727 proteins) than cortex regions (312 proteins) of
      Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral
      myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative
      phosphorylation, protein export, and drug metabolism-cytochrome P450 were the
      most commonly affected pathways of the three kinds of diseases. Almost coincident
      biological functions were identified in the brain tissues of the three diseases.
      In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob
      disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics
      changes at their terminal stages, which show the similarities not only among
      human prion diseases but also with other neurodegeneration diseases. This is the
      first study to provide a reference proteome map for human prion diseases and will
      be helpful for future studies focused on potential biomarkers for the diagnosis
      and therapy of human prion diseases. 

PMID- 25616866
TI  - Post-translational modifications regulate class IIa histone deacetylase (HDAC)
      function in health and disease.
AB  - Class IIa histone deacetylases (HDACs4, -5, -7, and -9) modulate the physiology
      of the human cardiovascular, musculoskeletal, nervous, and immune systems. The
      regulatory capacity of this family of enzymes stems from their ability to shuttle
      between nuclear and cytoplasmic compartments in response to signal-driven post
      translational modification. Here, we review the current knowledge of
      modifications that control spatial and temporal histone deacetylase functions by
      regulating subcellular localization, transcriptional functions, and cell cycle
      dependent activity, ultimately impacting on human disease. We discuss the
      contribution of these modifications to cardiac and vascular hypertrophy, myoblast
      differentiation, neuronal cell survival, and neurodegenerative disorders. 

PMID- 25616868
TI  - Importance of host cell arginine uptake in Francisella phagosomal escape and
      ribosomal protein amounts.
AB  - Upon entry into mammalian host cells, the pathogenic bacterium Francisella must
      import host cell arginine to multiply actively in the host cytoplasm. We
      identified and functionally characterized an arginine transporter (hereafter
      designated ArgP) whose inactivation considerably delayed bacterial phagosomal
      escape and intracellular multiplication. Intramacrophagic growth of the DeltaargP
      mutant was fully restored upon supplementation of the growth medium with excess
      arginine, in both F. tularensis subsp. novicida and F. tularensis subsp.
      holarctica LVS, demonstrating the importance of arginine acquisition in these two
      subspecies. High-resolution mass spectrometry revealed that arginine limitation
      reduced the amount of most of the ribosomal proteins in the DeltaargP mutant. In
      response to stresses such as nutritional limitation, repression of ribosomal
      protein synthesis has been observed in all kingdoms of life. Arginine
      availability may thus contribute to the sensing of the intracellular stage of the
      pathogen and to trigger phagosomal egress. All MS data have been deposited in the
      ProteomeXchange database with identifier PXD001584
      (http://proteomecentral.proteomexchange.org/dataset/PXD001584). 

PMID- 25616870
TI  - Cytoplasmic nucleation and atypical branching nucleation generate endoplasmic
      microtubules in Physcomitrella patens.
AB  - The mechanism underlying microtubule (MT) generation in plants has been primarily
      studied using the cortical MT array, in which fixed-angled branching nucleation
      and katanin-dependent MT severing predominate. However, little is known about MT
      generation in the endoplasm. Here, we explored the mechanism of endoplasmic MT
      generation in protonemal cells of Physcomitrella patens. We developed an assay
      that utilizes flow cell and oblique illumination fluorescence microscopy, which
      allowed visualization and quantification of individual MT dynamics. MT severing
      was infrequently observed, and disruption of katanin did not severely affect MT
      generation. Branching nucleation was observed, but it showed markedly variable
      branch angles and was occasionally accompanied by the transport of nucleated MTs.
      Cytoplasmic nucleation at seemingly random locations was most frequently observed
      and predominated when depolymerized MTs were regrown. The MT nucleator gamma
      tubulin was detected at the majority of the nucleation sites, at which a single
      MT was generated in random directions. When gamma-tubulin was knocked down, MT
      generation was significantly delayed in the regrowth assay. However, nucleation
      occurred at a normal frequency in steady state, suggesting the presence of a
      gamma-tubulin-independent backup mechanism. Thus, endoplasmic MTs in this cell
      type are generated in a less ordered manner, showing a broader spectrum of
      nucleation mechanisms in plants. 

PMID- 25616869
TI  - Proteomic analysis of the palmitate-induced myotube secretome reveals involvement
      of the annexin A1-formyl peptide receptor 2 (FPR2) pathway in insulin resistance.
AB  - Elevated levels of the free fatty acid palmitate are found in the plasma of obese
      patients and induce insulin resistance. Skeletal muscle secretes myokines as
      extracellular signaling mediators in response to pathophysiological conditions.
      Here, we identified and characterized the skeletal muscle secretome in response
      to palmitate-induced insulin resistance. Using a quantitative proteomic approach,
      we identified 36 secretory proteins modulated by palmitate-induced insulin
      resistance. Bioinformatics analysis revealed that palmitate-induced insulin
      resistance induced cellular stress and modulated secretory events. We found that
      the decrease in the level of annexin A1, a secretory protein, depended on
      palmitate, and that annexin A1 and its receptor, formyl peptide receptor 2
      agonist, played a protective role in the palmitate-induced insulin resistance of
      L6 myotubes through PKC-theta modulation. In mice fed with a high-fat diet,
      treatment with the formyl peptide receptor 2 agonist improved systemic insulin
      sensitivity. Thus, we identified myokine candidates modulated by palmitate
      induced insulin resistance and found that the annexin A1- formyl peptide receptor
      2 pathway mediated the insulin resistance of skeletal muscle, as well as systemic
      insulin sensitivity. 

PMID- 25616871
TI  - FASCIATED EAR4 encodes a bZIP transcription factor that regulates shoot meristem
      size in maize.
AB  - Plant architecture is dictated by precise control of meristematic activity. In
      the shoot, an imbalance in positive or negative maintenance signals can result in
      a fasciated or enlarged meristem phenotype. fasciated ear4 (fea4) is a
      semidwarfed mutant with fasciated ears and tassels as well as greatly enlarged
      vegetative and inflorescence meristems. We identified FEA4 as a bZIP
      transcription factor, orthologous to Arabidopsis thaliana PERIANTHIA. FEA4 was
      expressed in the peripheral zone of the vegetative shoot apical meristem and in
      the vasculature of immature leaves and conspicuously excluded from the stem cell
      niche at the tip of the shoot apical meristem and from incipient leaf primordia.
      Following the transition to reproductive fate, FEA4 was expressed throughout the
      entire inflorescence and floral meristems. Native expression of a functional
      YFP:FEA4 fusion recapitulated this pattern of expression. We used chromatin
      immunoprecipitation-sequencing to identify 4060 genes proximal to FEA4 binding
      sites, including ones that were potentially bound and modulated by FEA4 based on
      transcriptional changes in fea4 mutant ears. Our results suggest that FEA4
      promotes differentiation in the meristem periphery by regulating auxin-based
      responses and genes associated with leaf differentiation and polarity,
      potentially in opposition to factors such as KNOTTED1 and WUSCHEL. 

PMID- 25616872
TI  - The RING finger ubiquitin E3 ligase SDIR1 targets SDIR1-INTERACTING PROTEIN1 for
      degradation to modulate the salt stress response and ABA signaling in
      Arabidopsis.
AB  - The plant hormone abscisic acid (ABA) regulates many aspects of plant development
      and the stress response. The intracellular E3 ligase SDIR1 (SALT- AND DROUGHT
      INDUCED REALLY INTERESTING NEW GENE FINGER1) plays a key role in ABA signaling,
      regulating ABA-related seed germination and the stress response. In this study,
      we found that SDIR1 is localized on the endoplasmic reticulum membrane in
      Arabidopsis thaliana. Using cell biology, molecular biology, and biochemistry
      approaches, we demonstrated that SDIR1 interacts with and ubiquitinates its
      substrate, SDIRIP1 (SDIR1-INTERACTING PROTEIN1), to modulate SDIRIP1 stability
      through the 26S proteasome pathway. SDIRIP1 acts genetically downstream of SDIR1
      in ABA and salt stress signaling. In detail, SDIRIP1 selectively regulates the
      expression of the downstream basic region/leucine zipper motif transcription
      factor gene ABA-INSENSITIVE5, rather than ABA-RESPONSIVE ELEMENTS BINDING FACTOR3
      (ABF3) or ABF4, to regulate ABA-mediated seed germination and the plant salt
      response. Overall, the SDIR1/SDIRIP1 complex plays a vital role in ABA signaling
      through the ubiquitination pathway. 

PMID- 25616873
TI  - A maize glutaredoxin gene, abphyl2, regulates shoot meristem size and phyllotaxy.
AB  - Phyllotaxy describes the geometric arrangement of leaves and is important for
      plant productivity. Auxin is well known to regulate phyllotactic patterns via
      PIN1-dependent auxin polar transport, and studies of maize (Zea mays) aberrant
      phyllotaxy1 (abph1) mutants suggest the importance of auxin and cytokinin
      signaling for control of phyllotaxy. However, whether additional regulators
      control these patterns is poorly understood. Here, we report a new dominant maize
      mutant, Aberrant phyllotaxy2 (Abph2), in which the shoot meristems are enlarged
      and the phyllotactic pattern switches from alternate to decussate. Map-based
      cloning revealed that the Abph2 mutation was caused by transposition of a
      glutaredoxin gene, MALE STERILE CONVERTED ANTHER1 (MSCA1), which gained an
      altered expression pattern in Abph2 mutant embryos. msca1 loss-of-function
      mutants have reduced meristem size and revealed a novel function of glutaredoxins
      in meristem growth. In addition, MSCA1 interacts with a TGA transcription factor,
      FASCIATED EAR4, suggesting a novel regulatory module for regulating shoot
      meristem size. 

PMID- 25616874
TI  - A randomised controlled trial comparing compression therapy after radiofrequency
      ablation for primary great saphenous vein incompetence.
AB  - BACKGROUND: Optimal duration of leg compression after venous ablation remains
      unclear. This randomised controlled trial evaluates 4 h compared to 72 h of leg
      compression. METHODS: Patients were randomised to 4 or 72 h of leg compression
      after radiofrequency ablation of the great saphenous vein. Primary outcome was
      change in leg volume after 14 days. Secondary outcomes were postoperative pain,
      complications and time to full recovery. RESULTS: Patients wearing compression
      stockings for 4 h after treatment had a 64 mL (95%CI: - 23 to + 193) reduction in
      leg volume, compared to an increase of 21 mL (95%CI: 8.33-34.5) in patients
      wearing compression stockings for 72 h (P = 0.12). Patients wearing compression
      stockings for 4 h experienced fewer complications (16% vs. 33%, P = 0.05).
      Postoperative pain and time to full recovery did not differ significantly.
      CONCLUSION: Wearing compression stockings for 4 h is non-inferior in preventing
      leg oedema as wearing compression stockings for 72 h.

PMID- 25616875
TI  - [Current aspects of ototoxicity. Ototoxic substances and their effects].
AB  - Ototoxicity describes reversible or irreversible disorders of inner ear functions
      due to the influence of chemical, biological, or physical substances. Ototoxicity
      should be kept in mind during differential diagnosis of hearing loss, tinnitus,
      dizziness, and vertigo. In clinical practice, drug-induced ototoxic effects play
      a major role. The otorhinolaryngologist should also be involved in
      interdisciplinary cooperation, e.g., during treatment with antineoplastic
      chemotherapeutic agents with potential ototoxic side effects. In clinical
      practice, multimedication and interactions between different agents can
      complicate precise correlation in individual cases. Recent studies also show that
      noncellular components, such as otoconia, are extremely sensitive to chemical
      attacks. 

PMID- 25616877
TI  - Beyond tree-ring widths: stable isotopes sharpen the focus on climate responses
      of temperate forest trees.

PMID- 25616878
TI  - 2015: the year of the nurse continues.

PMID- 25616876
TI  - Prevalence of intestinal parasites, salmonella and shigella among apparently
      health food handlers of Addis Ababa University student's cafeteria, Addis Ababa,
      Ethiopia.
AB  - BACKGROUND: Food contamination may occur at any point during its journey through
      production, processing, distribution, and preparation. The risk of food getting
      contaminated depends largely on the health status of the food handlers, their
      personal hygiene, knowledge and practice of food hygiene. Food borne diseases are
      a public health problem in developed and developing countries like Ethiopia.
      METHOD: A cross sectional study was conducted among food handlers in Addis Ababa
      student's cafeteria from January to May 2013. Structured questionnaire was used
      to collect socio demographic data and associated risk factors. Stool specimens
      were examined for bacteria and intestinal parasites following standard
      procedures. Biochemical tests were done to identify the species of bacterial
      isolates. Sensitivity testing was done using Kirby- Baur disk diffusion method.
      RESULT: A total of 172 food handlers were enrolled in the study. The majority of
      study participants were females 134 (77.9%). About 78 (45.3%) of food handlers
      were found to be positive for different intestinal parasites with the most
      abundant parasite of Entameoba histolytica/dispar 68 (70.8%) followed by Giardia
      lamblia 18 (18.8%), Taenia species 5 (5.2%), Ascaris lumbricoides 2 (2.1%),
      hookworm 2 (2.1%) and Trichuris trichiura 1 (1.1%). Stool cultures revealed 3.5%
      of Salmonella isolates (Sero-grouping on Salmonella isolate was not done), while
      Shigella species was not isolated from any of the stool samples obtained from
      Food handlers. All isolates of Salmonella were sensitive to ciprofloxacin,
      amikacin and gentamicin but resistant to ampicillin, clindamycin, and
      erythromycin. CONCLUSION: The present study revealed a high prevalence of
      intestinal parasite in asymptomatic (apparently health) food handlers. Such
      infected food handlers can contaminate food, drinks and could serve as source of
      infection to consumers via food chain.

PMID- 25616879
TI  - Music during surgery.

PMID- 25616881
TI  - A comparison of two differing doses of promethazine for the treatment of
      postoperative nausea and vomiting.
AB  - PURPOSE: To compare the use of promethazine 6.25 mg intravenous (IV)
      (experimental group) with promethazine 12.5 mg IV (control group) among adult
      ambulatory surgery patients to control established postoperative nausea or
      vomiting (PONV). DESIGN/METHODS: In a double-blind, randomized controlled trial
      (n = 120), 59 subjects received promethazine 6.25 mg and 61 subjects received
      promethazine 12.5 mg to treat PONV. Study doses were administered postoperatively
      if the subject reported/exhibited nausea and/or vomiting. Outcomes for
      experimental and control groups were compared on the basis of relief of PONV and
      sedation levels. FINDINGS: Ninety-seven percent of subjects reported total relief
      of nausea with a single administration of promethazine at either dose. Sedation
      levels differed between groups at 30 minutes post-medication administration and
      at the time of discharge to home. CONCLUSIONS: Promethazine 6.25 mg is as
      effective in controlling PONV as promethazine 12.5 mg, while resulting in less
      sedation.

PMID- 25616882
TI  - Capnography (ETCO2), respiratory depression, and nursing interventions in
      moderately sedated adults undergoing transesophageal echocardiography (TEE).
AB  - PURPOSE: Little attention has been paid to the safety of moderate sedation given
      to adult patients undergoing transesophageal echocardiography (TEE). Although
      capnography has been found to indicate respiratory depression earlier than pulse
      oximetry in other sedation scenarios, its usefulness during TEE has not been
      clearly documented. DESIGN: A prospective, single-group, observational design was
      used. METHODS: A total of 200 adult patients undergoing TEE with moderate
      sedation were studied. Patient demographic and procedural physiologic variables,
      types and doses of sedating medications administered, incidence of respiratory
      depression, and types and effectiveness of nursing interventions delivered when
      subjects experienced respiratory depression were examined. FINDING: Respiratory
      depression identified by capnography occurred in 45% of the subjects. Capnography
      provided earlier identification of respiratory depression than pulse oximetry.
      Hydromorphone was associated with respiratory depression more so than other
      agents; whereas nursing interventions were effective in preventing more serious
      cardiorespiratory compromise. CONCLUSIONS: Capnography, as a tool to provide
      early warning of respiratory depression or airway compromise, has the potential
      to further decrease the incidence of serious adverse events due to inadvertent
      oversedation.

PMID- 25616883
TI  - Perioperative nurses' attitudes toward the electronic health record.
AB  - BACKGROUND: The adoption of an electronic health record (EHR) is mandated under
      current health care legislation reform. The EHR provides data that are patient
      centered and improves patient safety. There are limited data; however, regarding
      the attitudes of perioperative nurses toward the use of the EHR. PURPOSE: The
      purpose of this project was to identify perioperative nurses' attitudes toward
      the use of the EHR. DESIGN: Quantitative descriptive survey was used to determine
      attitudes toward the electronic health record. METHODS: Perioperative nurses in a
      southeastern health system completed an online survey to determine their
      attitudes toward the EHR in providing patient care. FINDINGS: Overall,
      respondents felt the EHR was beneficial, did not add to the workload, improved
      documentation, and would not eliminate any nursing jobs. CONCLUSIONS: Nursing
      acceptance and the utilization of the EHR are necessary for the successful
      integration of an EHR and to support the goal of patient-centered care.
      Identification of attitudes and potential barriers of perioperative nurses in
      using the EHR will improve patient safety, communication, reduce costs, and
      empower those who implement an EHR.

PMID- 25616884
TI  - Prewarming in a pediatric hospital: process improvement through interprofessional
      collaboration.
AB  - A quality improvement project intended to promote maintenance of normothermia
      through active prewarming was carried out at a pediatric specialty hospital. An
      alternative active, forced-air warming product (Bair Paws warming gowns) was
      trialed in place of the existing active warming product (Bair Hugger blankets).
      Converting to the new product was intended to improve patient and staff
      compliance with prewarming recommendations. The alternative forced air active
      warming product was favored by both staff and patients, and the rate of
      compliance with this practice nearly doubled following the change in product.
      Extensive interprofessional collaboration and problem solving were required to go
      from an idea to a fully implemented change. The project demonstrated the
      importance of collaboration among various disciplines and the positive impact
      interprofessional collaboration can have on compliance with practice changes.

PMID- 25616885
TI  - Magnet journey: a quality improvement project-implementation of family visitation
      in the PACU.
AB  - PURPOSE: Over the years, patient- and family-centered care has been a focus of
      many researchers in the postanesthesia care unit (PACU) setting. Despite evidence
      pointing to the benefits and positive outcomes of partnering with family in
      patient care in pediatric and adult PACUs, this practice has not gained
      popularity in the adult PACUs of many hospitals. The purpose of this project was
      to test and validate the benefits of including families as partners in care in
      the PACU. DESIGN: A pre/post exploratory design using survey methodology was
      used. METHODS: Survey questionnaires were administered to patients, family, and
      nursing staff before and after the implementation of a patient visitation
      program. FINDINGS: Patient and family satisfaction increased after implementation
      of the family visitation program. Nursing satisfaction with and openness to
      family visitation also increased. CONCLUSIONS: Results provide the evidence base
      to implement an open visitation policy that has been made permanent as a standard
      of care practiced in all the PACU sites throughout the health system.

PMID- 25616886
TI  - Foreign body aspiration: a life-threatening situation.
AB  - Foreign body aspiration is a life-threatening event, especially in children. In
      Pakistan, foreign body aspiration in children with betel nuts is a common
      emergency in the perioperative area. Health awareness of parents, teachers,
      caretakers, and health care providers can play a significant role in reducing the
      risk of this life-threatening event. This article describes a case report of a
      21/2 year old boy who presented in the perioperative area with a betel nut
      aspiration. 

PMID- 25616887
TI  - Determining the appropriate location and level of care for a postanesthesia
      and/or postsedation patient.
AB  - There are a number of methods that can be used to determine the best phase of
      care for a postanesthesia/post-sedation patient. Policies and procedures
      developed in collaboration with one's anesthesia department should be the primary
      reference for determining the phase of care required for each patient. The ASPAN
      Perianesthesia Standards, Practice Recommendations and Interpretive Statements
      can also guide patient care by recommending what each patient needs in terms of
      assessments and interventions. It is important to remember that the patient
      requires a level of care, not a particular location. And finally, nurse
      creativity in trying new methods can enhance the patient's care and progression
      to a safe discharge.

PMID- 25616888
TI  - Tracheal intubation with a flexible intubation scope versus other intubation
      techniques for obese patients requiring general anesthesia.

PMID- 25616890
TI  - Virtually sensing the future of perianesthesia nursing.

PMID- 25616891
TI  - Unconventional use of a PCA pump: nurse-activated dosing.
AB  - Creative approaches, such as NAD, can be taken to manage pain in patients who
      would be candidates for PCA therapy if they were physically and cognitively able
      to manage their own pain. NAD authorizes the patient's primary nurse to
      administer bolus doses with or without a basal rate via the PCA infusion pump.
      Doses are administered for breakthrough pain with a basal rate or in scheduled
      doses to maintain analgesia without a basal rate. It is also used to administer
      bolus doses before and during painful procedures.

PMID- 25616892
TI  - Music.

PMID- 25616893
TI  - Anesthesia outside the operating room in adults: a matter of safety?: guest
      editorial.

PMID- 25616894
TI  - Decatransin, a new natural product inhibiting protein translocation at the
      Sec61/SecYEG translocon.
AB  - A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with
      potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S.
      cerevisiae indicated that the Sec61 translocon complex, the machinery for protein
      translocation and membrane insertion at the endoplasmic reticulum, is the target.
      The profiles were similar to those of cyclic heptadepsipeptides of a distinct
      chemotype (including HUN-7293 and cotransin) that had previously been shown to
      inhibit cotranslational translocation at the mammalian Sec61 translocon.
      Unbiased, genome-wide mutagenesis followed by full-genome sequencing in both
      fungal and mammalian cells identified dominant mutations in Sec61p (yeast) or
      Sec61alpha1 (mammals) that conferred resistance. Most, but not all, of these
      mutations affected inhibition by both chemotypes, despite an absence of
      structural similarity. Biochemical analysis confirmed inhibition of protein
      translocation into the endoplasmic reticulum of both co- and post-translationally
      translocated substrates by both chemotypes, demonstrating a mechanism independent
      of a translating ribosome. Most interestingly, both chemotypes were found to also
      inhibit SecYEG, the bacterial Sec61 translocon homolog. We suggest 'decatransin'
      as the name for this new decadepsipeptide translocation inhibitor. 

PMID- 25616896
TI  - Assembly and quality control of the protein phosphatase 1 holoenzyme involves the
      Cdc48-Shp1 chaperone.
AB  - Protein phosphatase 1 (PP1) controls many aspects of cell physiology, which
      depends on its correct targeting in the cell. Nuclear localization of Glc7, the
      catalytic subunit of PP1 in budding yeast, requires the AAA-ATPase Cdc48 and its
      adaptor Shp1 through an unknown mechanism. Herein, we show that mutations in SHP1
      cause misfolding of Glc7 that co-aggregates with Hsp104 and Hsp42 chaperones and
      requires the proteasome for clearance. Mutation or depletion of the PP1
      regulatory subunits Sds22 and Ypi1, which are involved in nuclear targeting of
      Glc7, also produce Glc7 aggregates, indicating that association with regulatory
      subunits stabilizes Glc7 conformation. Use of a substrate-trap Cdc48(QQ) mutant
      reveals that Glc7-Sds22-Ypi1 transiently associates with and is the major target
      of Cdc48-Shp1. Furthermore, Cdc48-Shp1 binds and prevents misfolding of PP1-like
      phosphatases Ppz2 and Ppq1, but not other types of phosphatases. Our data suggest
      that Cdc48-Shp1 functions as a molecular chaperone for the structural integrity
      of PP1 complex in general and that it specifically promotes the assembly of Glc7
      Sds22-Ypi1 for nuclear import. 

PMID- 25616895
TI  - The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity.
AB  - Cranial neural crest (CNC) cells are a transient population of stem cells that
      originate at the border of the neural plate and the epidermis, and migrate
      ventrally to contribute to most of the facial structures including bones,
      cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is
      essential for CNC cell migration. Here, we show in Xenopus laevis embryos that
      the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively
      regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC
      cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4
      function also inhibits CNC cell migration and induces a reduction of mature
      ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is
      known to translocate into the nucleus to regulate gene expression. We propose
      that Fz4 associates with ADAM13 during its transport to the plasma membrane to
      regulate its proteolytic activity. 

PMID- 25616897
TI  - Downregulation of E2F1 during ER stress is required to induce apoptosis.
AB  - The endoplasmic reticulum (ER) has recently emerged as an alternative target to
      induce cell death in tumours, because prolonged ER stress results in the
      induction of apoptosis even in chemoresistant transformed cells. Here, we show
      that the DNA-damage-responsive pro-apoptotic factor E2F1 is unexpectedly
      downregulated during the ER stress-mediated apoptotic programme. E2F1 decline is
      a late event during the ER response and is mediated by the two unfolded protein
      response (UPR) sensors ATF6 and IRE1 (also known as ERN1). Whereas ATF6 directly
      interacts with the E2F1 promoter, IRE1 requires the involvement of the known E2F1
      modulator E2F7, through the activation of its main target Xbp-1. Importantly,
      inhibition of the E2F1 decrease prevents ER-stress-induced apoptosis, whereas
      E2F1 knockdown efficiently sensitises cells to ER stress-dependent apoptosis,
      leading to the upregulation of two main factors in the UPR pro-apoptotic
      execution phase, Puma and Noxa (also known as BBC3 and PMAIP1, respectively). Our
      results point to a novel key role of E2F1 in the cell survival/death decision
      under ER stress, and unveil E2F1 inactivation as a valuable novel potential
      therapeutic strategy to increase the response of tumour cells to ER stress-based
      anticancer treatments. 

PMID- 25616898
TI  - A maternal effect rough deal mutation suggests that multiple pathways regulate
      Drosophila RZZ kinetochore recruitment.
AB  - Proper kinetochore recruitment and regulation of dynein and the Mad1-Mad2 complex
      requires the Rod-Zw10-Zwilch (RZZ) complex. Here, we describe rod(Z3), a maternal
      effect Drosophila mutation changing a single residue in the Rough Deal (Rod)
      subunit of RZZ. Although the RZZ complex containing this altered subunit (denoted
      R(Z3)ZZ) is present in early syncytial stage embryos laid by homozygous rod(Z3)
      mothers, it is not recruited to kinetochores. Consequently, the embryos have no
      spindle assembly checkpoint (SAC), and syncytial mitoses are profoundly
      perturbed. The polar body (residual meiotic products) cannot remain in its SAC
      dependent metaphase-like state, and decondenses into chromatin. In neuroblasts of
      homozygous rod(Z3) larvae, R(Z3)ZZ recruitment is only partially reduced, the SAC
      is functional and mitosis is relatively normal. R(Z3)ZZ nevertheless behaves
      abnormally: it does not further accumulate on kinetochores when microtubules are
      depolymerized; it reduces the rate of Mad1 recruitment; and it dominantly
      interferes with the dynein-mediated streaming of RZZ from attached kinetochores.
      These results suggest that the mutated residue of rod(Z3) is required for normal
      RZZ kinetochore recruitment and function and, moreover, that the RZZ recruitment
      pathway might differ in syncytial stage embryos and post-embryonic somatic cells.

PMID- 25616899
TI  - Hypoxia increases the abundance but not the assembly of extracellular fibronectin
      during epithelial cell transdifferentiation.
AB  - Increased production and assembly of extracellular matrix proteins during
      transdifferentiation of epithelial cells to a mesenchymal phenotype contributes
      to diseases such as renal and pulmonary fibrosis. TGF-beta and hypoxia, two cues
      that initiate injury-induced fibrosis, caused human kidney cells to develop a
      mesenchymal phenotype, including increased fibronectin expression and secretion.
      However, upon hypoxia, assembled extracellular fibronectin fibrils were mostly
      absent, whereas treatment with TGF-beta led to abundant fibrils. Fibrillogenesis
      required cell-generated force and tension. TGF-beta, but not hypoxia, increased
      cell contractility, as determined by phosphorylation of myosin light chain and
      quantifying force and tension generated by cells plated on engineered elastomeric
      microposts. Additionally, TGF-beta, but not hypoxia, increased the activation of
      integrins. However, experimentally activating integrins markedly increased the
      levels of phosphorylated myosin light chain and fibronectin fibril assembly upon
      hypoxia. Our findings show that deficient integrin activation and subsequent lack
      of cell contractility are mechanisms that mediate a lack of fibrillogenesis upon
      hypoxia and they challenge current views on oxygen deprivation being sufficient
      for fibrosis. 

PMID- 25616900
TI  - Sharing the cell's bounty - organelle inheritance in yeast.
AB  - Eukaryotic cells replicate and partition their organelles between the mother cell
      and the daughter cell at cytokinesis. Polarized cells, notably the budding yeast
      Saccharomyces cerevisiae, are well suited for the study of organelle inheritance,
      as they facilitate an experimental dissection of organelle transport and
      retention processes. Much progress has been made in defining the molecular
      players involved in organelle partitioning in yeast. Each organelle uses a
      distinct set of factors - motor, anchor and adaptor proteins - that ensures its
      inheritance by future generations of cells. We propose that all organelles,
      regardless of origin or copy number, are partitioned by the same fundamental
      mechanism involving division and segregation. Thus, the mother cell keeps, and
      the daughter cell receives, their fair and equitable share of organelles. This
      mechanism of partitioning moreover facilitates the segregation of organelle
      fragments that are not functionally equivalent. In this Commentary, we describe
      how this principle of organelle population control affects peroxisomes and other
      organelles, and outline its implications for yeast life span and rejuvenation. 

PMID- 25616901
TI  - [Implementation of the 5S quality control management scheme to the Ouidah
      hospital zone in Benin].
AB  - BACKGROUND: Delivery of quality care remains a major challenge for all heathcare
      institutions. The 5S quality control scheme was applied in the Ouidah hospital
      zone in Benin starting in 2012. The objective of the present survey was to
      evaluate its impact in 2013. METHODS: This was a descriptive and analytic survey
      of the Ouidha hospital zone. Three techniques - interview, observation, review -
      were used to collect data from the healthcare staff, hospital users, and
      documents describing the strategy of the implementation. RESULTS: Implementation
      of the 5S strategy was considered, on average, to be "satisfactory" with scores
      of 56% for context, 61% for inputs, and 51% for processes. The internal and
      external users judged care delivery "very satisfactory" with a score of 79%.
      CONCLUSION: Although the results appear satisfactory, the future hospital policy
      must strengthen the quality insurance process, ensure the availability of
      management tools, and provide training and further motivation for the "5S"
      management teams.

PMID- 25616902
TI  - Discovery of 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines as potent PIM
      inhibitors.
AB  - PIM kinases are a family of Ser/Thr kinases that are implicated in tumorigenesis.
      The discovery of a new class of PIM inhibitors, 5-(1H-indol-5-yl)-1,3,4
      thiadiazol-2-amines, is discussed with optimized compounds showing excellent
      potency against all three PIM isoforms. 

PMID- 25616903
TI  - Synthesis and transmembrane anion/cation symport activity of a rigid bis(choloyl)
      conjugate functionalized with guanidino groups.
AB  - A rigid bis(choloyl) conjugate functionalized with guanidino groups was
      synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI
      MS (LR and HR) data. Its transmembrane ionophoric activity across egg-yolk l
      alpha-phosphatidylcholine-based liposomal membranes was investigated by means of
      chloride ion selective electrode technique and pH discharge assay. The data
      indicate that under the assay conditions, this conjugate was capable of promoting
      the transport of anions, presumably via a cation/anion symport process. A Hill
      analysis reveals that two molecules of this compound are assembled into the
      transport-active species. 

PMID- 25616904
TI  - Ebselen Attenuates Lung Injury in Experimental Model of Carrageenan-Induced
      Pleurisy in Rats.
AB  - The study evaluates the role of Ebselen (Eb), an organoselenium compound in
      animal model of acute lung injury induced by carrageenan (CG). Wistar rats
      received saline or 2 % lambda-carrageenan in the pleural cavity, and treatment
      with Eb (50 mg/kg intragastrically) or dexamethasone (Dx) (0.5 mg/kg
      intraperitoneal) after CG administration. After 4 h, rats were euthanized and the
      pleural exudate removed for analysis of the total cell count, total protein,
      lactate dehydrogenase, and nitrite/nitrate. Moreover, lung tissue were removed to
      verify the myeloperoxidase activity and oxidative damage. Eb showed anti
      inflammatory activity by inhibiting leukocyte influx, myeloperoxidase activity,
      and nitrite/nitrate concentration. Eb presented with an anti-inflammatory
      activity similar to Dx and an antioxidant activity better than Dx. This study
      suggests that Eb plays an important role against the oxidative damage associated
      with anti-inflammatory activity in animal model of acute lung injury, proving to
      be similar or potentially more effective than Dx. 

PMID- 25616905
TI  - Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress
      and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS
      Signaling.
AB  - Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti
      inflammatory activity. Here, we investigated the effects of arctigenin on
      lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four
      groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS +
      Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h
      before an intratracheal administration of LPS (5 mg/kg). Lung tissues and
      bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the
      lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS
      induced acute lung inflammation, infiltration of inflammatory cells into BALF,
      and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment
      reduced the malondialdehyde level and increased superoxide dismutase and catalase
      activities and glutathione peroxidase/glutathione disulfide ratio in the lung.
      Mechanically, arctigenin significantly reduced the production of nitric oxygen
      and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression
      of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated
      protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative
      effects on LPS-induced acute lung injury, which are associated with modulation of
      MAPK, HO-1, and iNOS signaling. 

PMID- 25616906
TI  - Activation of Nicotinic Receptors Inhibits TNF-alpha-Induced Production of Pro
      inflammatory Mediators Through the JAK2/STAT3 Signaling Pathway in Fibroblast
      Like Synoviocytes.
AB  - It was recently demonstrated that stimulation of the nicotine receptor attenuates
      collagen-induced arthritis and inhibits cytokine release in mice. We elucidated
      the possible intracellular signaling mechanism of the cholinergic anti
      inflammatory pathway in fibroblast-like synoviocytes (FLSs). Levels of
      interleukin (IL)-6, IL-10, and monocyte chemoattractant protein (MCP)-1 in
      culture supernatants of tumor necrosis factor (TNF)-alpha-stimulated FLSs were
      measured using an enzyme-linked immunosorbent assay (ELISA). FLSs were
      transfected with a small interfering RNA oligonucleotide (STAT3 siRNA or control
      siRNA). AG490, a specific inhibitor of JAK2, was added 16 h before nicotine, and
      blocker of nAChR was added 30 min before nicotine. Activation of signal
      transducers and activators of transcription (STAT) such as STAT1 and STAT3 were
      detected using Western blotting. Nicotine downregulated production of IL-6 and
      MCP-1 in RA-FLSs induced by TNFalpha in a concentration-dependent manner, and IL
      10 levels were not significantly different after nicotine pretreatment. Nicotine
      induced activation of STAT3 (but not STAT1) and deactivation of STAT3 decreased
      the anti-inflammatory effect of nicotine. AG490 inhibited the phosphorylation of
      STAT1 and STAT3 and decreased the TNF-alpha-induced production of pro
      inflammatory mediators in RA-FLSs. A alpha7nAChR antagonist abrogated the anti
      inflammatory effects of nicotine and suppressed STAT3 activity. In conclusion,
      nicotine has an anti-inflammatory effect on RA by downregulating production of IL
      6 and MCP-1 in FLSs, and this is mediated through activation of the JAK2-STAT3
      signal pathway. 

PMID- 25616907
TI  - Efficacy and durability of the chimney graft technique in urgent and complex
      thoracic endovascular aortic repair.
AB  - OBJECTIVE: This study reports the early and midterm to long-term experience of
      chimney grafts (CGs) in urgent endovascular repair of complex lesions in the
      thoracic aorta. METHODS: Twenty-nine high-risk patients (20 men) who were unfit
      for open repair were treated using CG technique for ruptured (n = 14) or
      symptomatic (n = 15) aortic lesions engaging the aortic arch itself (n = 9), the
      descending aorta (n = 10), or the thoracoabdominal aorta (n = 10). Twenty-two
      patients (76%) were treated urgently (<=24 hours) and seven were semiurgent (<=3
      days). Of 41 chimneys used, 24 were placed in supra-aortic branches and 17 in
      visceral branches. Median follow-up (interquartile range) for the entire cohort
      was 2 years (0.6-3.8 years), 2.5 years (1-4 years) for 30-day survivors, and 3.5
      years (1.9-6.4 years) for those who were still alive. RESULTS: Four patients
      (14%) died <=30 days of cerebral infarction (n = 1), visceral ischemia secondary
      to the initial rupture (n = 1), multiple organ failure (n = 1), or heart failure
      (n = 1). There were 11 late deaths (38%); however, only two deaths were related
      to the CG technique. The primary and secondary technical success rates were 86%
      (25 of 29) and 97% (28 of 29), respectively. The secondary patency rate of CGs
      was 98%. Seventeen (68%) of the aortic lesions shrank significantly. Three
      patients (10%) had primary type I endoleak and another three (10%) had secondary
      type I endoleak. The endoleaks were managed with Onyx (ev3 Endovascular, Inc,
      Plymouth, Minn) or coil embolization (n = 2), restenting (n = 1), and conversion
      to open repair (n = 2). One secondary endoleak is still under observation after
      >20 months. All primary endoleaks and one secondary endoleak originated from CGs
      in the brachiocephalic trunk (4 of 6 [67%]). CONCLUSIONS: The midterm to long
      term results of the CG technique for urgent and complex lesions of the thoracic
      aorta in high-risk patients are promising, with low early mortality and long
      durability of the CGs. More patients with longer follow-up are still needed.

PMID- 25616908
TI  - Erratum to: Sorafenib-Associated Facial Acneiform Eruption.

PMID- 25616909
TI  - Microbiological functioning, diversity, and structure of bacterial communities in
      ultramafic soils from a tropical savanna.
AB  - Ultramafic soils are characterized by high levels of metals, and have been
      studied because of their geochemistry and its relation to their biological
      component. This study evaluated soil microbiological functioning (SMF), richness,
      diversity, and structure of bacterial communities from two ultramafic soils and
      from a non-ultramafic soil in the Brazilian Cerrado, a tropical savanna. SMF was
      represented according to simultaneous analysis of microbial biomass C (MBC) and
      activities of the enzymes beta-glucosidase, acid phosphomonoesterase and
      arylsulfatase, linked to the C, P and S cycles. Bacterial community diversity and
      structure were studied by sequencing of 16S rRNA gene clone libraries. MBC and
      enzyme activities were not affected by high Ni contents. Changes in SMF were more
      related to the organic matter content of soils (SOM) than to their available Ni.
      Phylogeny-based methods detected qualitative and quantitative differences in
      pairwise comparisons of bacterial community structures of the three sites.
      However, no correlations between community structure differences and SOM or SMF
      were detected. We believe this work presents benchmark information on SMF,
      diversity, and structure of bacterial communities for a unique type of
      environment within the Cerrado biome. 

PMID- 25616910
TI  - Chryseobacterium profundimaris sp. nov., a new member of the family
      Flavobacteriaceae isolated from deep-sea sediment.
AB  - A Gram-stain negative, strictly aerobic, rod-shaped, non-motile bacterium,
      designated strain DY46(T), was isolated from Atlantic Ocean sediment. The isolate
      was found to grow in medium containing 0-3.0 % (w/v) NaCl (optimally at 0-1.0 %),
      at 4-37  degrees C and pH 5.0-8.0. Chemotaxonomic analysis detected MK-6 as the
      sole isoprenoid quinone. The major fatty acids were identified iso-C15:0, iso
      C17:0 3-OH, iso-C17:1 omega9c and summed feature 3 (comprising iso-C15:0 2-OH
      and/or C16:1 omega7c). The DNA G + C content was determined to be 40.7 mol %.
      Phylogenetic analyses based on the 16S rRNA gene sequence indicated that strain
      DY46(T) falls within the cluster comprising Chryseobacterium species. The levels
      of 16S rRNA gene sequence similarity between strain DY46(T) and the type strains
      of the Chryseobacterium species with validly published names ranged from 92.4 to
      99.1 %, the high values (>97 %) being with Chryseobacterium takakiae A1-2(T)
      (99.1 %), C. taiwanense BCRC 17412(T) (98.0 %), C. taeanense PHA3-4(T) (97.3 %),
      C. hispalense DSM 25574(T) (97.3 %), C. camelliae THG C4-1(T) (97.2 %), C.
      gregarium DSM 19109(T) (97.1 %) and C. wanjuense R2A10-2(T) (97.0 %). The DNA-DNA
      relatedness values between strain DY46(T) and the type strains of the above
      closely related species were 47, 57, 24, 34, 6, 40 and 21 %, respectively. On the
      basis of phenotypic and genotypic characteristics, strain DY46(T) represents a
      novel member within the genus Chryseobacterium, for which the name
      Chryseobacterium profundimaris is proposed. The type strain is DY46(T) (=CGMCC
      1.12663(T) = JCM 19801(T)). 

PMID- 25616911
TI  - Age-related development and tissue distribution of T cell markers (CD4 and CD8a)
      in Chinese goose.
AB  - Aquatic birds play n critical role in the transmission and dissemination of many
      important pathogens such as avian influenza virus. The cell-mediated immunity is
      very important in eliminating the intracellular antigens. Expression of CD4 and
      CD8 on T cell surface is essential for cell-mediated immune defence and T-cell
      development. However, the ontogeny of T lymphocytes in waterfowl is scarce and
      fragmentary. To address these questions, here we report the development and
      tissues distribution of CD4 and CD8alpha in goose embryo, gosling and goose by
      immunocytochemistry assay using monoclonal antibodies. Moreover, the age-related
      mRNA level of goose CD4 and CD8alpha in different immune tissues were study by
      real time quantitative PCR. Our results suggested that the high expression of CD4
      and CD8alpha were readily found in thymus, which peaked at the first week post
      hatch. And the highest expression level of CD4 and CD8alpha were detected in
      bursa of Fabricius, caecal tonsils, spleen and intestine at the second week,
      after that the expression level were gradually decreased. Interestingly, the
      remarkably high expression of CD4 and CD8alpha in Harderian gland were detected
      at the first week, which is about hundreds times more than that in other tissues.
      Our findings demonstrated that the development and the distribution of CD4 and
      CD8alpha are partly changed in an age-related way. Moreover, the histological
      morphogenesis of immune tissues were also discussed. Our results may shed lights
      on the better understand of T-cell mediate immunity in goose. 

PMID- 25616913
TI  - Breastfeeding infants with congenital torticollis.
AB  - Infants with unilateral sternocleidomastoid tension and associated craniofacial,
      spinal, and hip asymmetries may feed poorly. Anatomic and muscular asymmetry
      stress both biomechanics and state control, increasing the potential for
      difficulty latching and sucking. A combination of positioning modifications to
      allow the infant to maintain his or her comfortable head tilt and turn,
      supportive techniques to restore alignment of oral structures, and handling
      techniques to help activate the weak contralateral muscles have been effective in
      the author's practice. Lactation consultants can promote positioning and muscle
      activation strategies and encourage physical therapy referrals for infants who do
      not respond promptly to reduce the risk of craniofacial deformity and
      developmental problems. 

PMID- 25616912
TI  - Isolation and characterization of antibody fragments selective for toxic
      oligomeric tau.
AB  - Oligomeric tau species are important in the onset and progression of Alzheimer's
      disease (AD), as they are neurotoxic and can propagate tau-tangle pathology.
      Therefore, reagents that selectively recognize different key morphologies of tau
      are needed to help define the role of tau in AD and related diseases. We utilized
      a biopanning protocol that combines the binding diversity of phage-displayed
      antibody libraries with the powerful imaging capability of atomic force
      microscopy to isolate single-chain antibody fragments (scFvs) that selectively
      bind toxic oligomeric tau. We isolated 3 different antibody fragments that bind
      oligomeric but not monomeric or fibrillar tau. The scFvs differentiate brain
      tissue homogenates of both 3*TG and tau-AD mice from wild-type mice, detecting
      oligomeric tau at much earlier ages than when neurofibrillary tangles are
      typically detected. The scFvs also distinguish human postmortem AD brain tissue
      from cognitively normal postmortem human brain tissue, demonstrating the
      potential of this approach for developing biomarkers for early detection and
      progression of AD. 

PMID- 25616915
TI  - Erratum to: is the lateralization distance important in terms in patients
      undergoing the modified Limberg flap procedure for treatment of pilonidal sinus?

PMID- 25616914
TI  - Unipolar versus bipolar hemiarthroplasty for displaced femoral neck fractures: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Whether bipolar hemiarthroplasty (BH) for displaced femoral neck
      fractures has benefit over unipolar hemiarthroplasty (UH) remains controversial.
      We conducted a systematic review and meta-analysis of randomized controlled
      trials (RCTs) to evaluate the relative effects between BH and UH. METHODS: A
      systematic literature search (up to April, 2014) was conducted to include RCTs
      comparing BH with UH for displaced femoral neck fractures. Two authors
      independently assessed methodological quality of the included studies and
      extracted data. Surgical information and postoperative outcomes were analyzed.
      RESULTS: A total of 10 RCTs including 1,190 patients were indentified. Our
      results demonstrated that BH was associated with similar or better outcomes in
      hip function, hip pain, and quality of life while with a higher cost compared
      with UH. Moreover, there were no significant differences between BH and UH with
      regard to operation time, blood loss, blood transfusion, hospital stay,
      mortality, reoperation, dislocation, and complications. BH could significantly
      decrease the incidence of acetabular erosion at 1 year follow-up compared with UH
      (RR = 0.24, 95% confidence interval (CI) = 0.06 to 0.89, P = 0.03), but no
      significant difference was observed at 4 months, 2 years, and 4 years follow-ups.
      CONCLUSIONS: Based on the current evidence, BH is not superior to UH in terms of
      surgical information and postoperative results. Despite similar or better
      clinical outcomes compared with UH, BH with a higher cost could not decrease long
      term acetabular erosion rate.

PMID- 25616916
TI  - Complete response of acquired FV inhibitor to rituximab.

PMID- 25616917
TI  - Preventive stenting in acute myocardial infarction.
AB  - Current practice guidelines advocate culprit vessel intervention alone in
      patients with ST-segment elevation myocardial infarction (STEMI) found to have
      multivessel coronary disease during primary percutaneous coronary intervention
      (PCI). The debate on the timing of noninfarct artery intervention has recently
      been reinvigorated by the PRAMI (Preventive Angioplasty in Acute Myocardial
      Infarction) trial, in which patients undergoing preventive PCI of significant
      nonculprit lesions at the time primary PCI for STEMI had reduced rates of cardiac
      death, nonfatal myocardial infarction, and refractory angina. Given that previous
      literature has cautioned against multivessel PCI during STEMI, this raises the
      question of whether technical and pharmacological advances in PCI may have opened
      the door to safely revisit this issue with additional clinical rigor. The impact
      of STEMI pathophysiology on nonculprit vessel plaque, how treatment of nonculprit
      lesions alters the natural history of coronary disease after STEMI, and whether
      this results in a clinical benefit remain unclear, and much of the existing data
      are retrospective. Additionally, the PRAMI trial did not include a staged PCI,
      leaving questions as to how this approach might fare compared with simultaneous
      preventive PCI. In this review, we discuss the pathophysiology of nonculprit
      vessel plaque in STEMI, provide a summary of the existing literature on the
      topic, and discuss the PRAMI trial in the face of previous data and possible
      future directions for further study. 

PMID- 25616918
TI  - Increasing percutaneous coronary interventions for ST-segment elevation
      myocardial infarction in the United States: progress and opportunity.
AB  - OBJECTIVES: The aim of this study was to quantify changes in percutaneous
      coronary intervention (PCI) and mortality rates for ST-segment elevation
      myocardial infarction (STEMI), and the proportion of hospitals providing STEMI
      related PCI in the United States. BACKGROUND: Health care systems have recently
      emphasized rapid access to PCI for STEMI, but the effects of these efforts in a
      broad population are unknown. METHODS: We used the Nationwide Inpatient Sample, a
      discharge database representative of all short-term, nonfederal hospitals in the
      United States. STEMI discharges were included based on primary discharge
      diagnosis. We calculated the adjusted odds ratio (OR) of PCI and in-hospital
      death over time and the changing proportion of hospitals providing STEMI-related
      PCI. RESULTS: From 2003 to 2011, STEMI accounted for 380,254 hospital discharges.
      The rate of PCI increased from 53.6% to 80.0% with an adjusted OR of 4.16 (95%
      confidence interval [CI]: 3.71 to 4.66) in 2011 compared with 2003. The
      proportion of hospitals providing STEMI-related PCI increased from 25.1% in 2003
      to 33.7% in 2011. In-hospital death rates ranged from 7.2% to 9.5%, with the
      lowest rate in 2009. The OR of death decreased from 2003 to 2011 (adjusted OR:
      0.79 in 2011 compared with 2003; 95% CI: 0.74 to 0.84). After accounting for PCI,
      the OR of in-hospital death did not change between 2003 and 2011 (adjusted OR:
      1.01 in 2011 compared with 2003; 95% CI: 0.95 to 1.07). CONCLUSIONS: PCI rates
      and hospitals providing STEMI-related PCI increased from 2003 to 2011, whereas in
      hospital death rates decreased. PCI was an important mediator of decreasing
      mortality in this nationally representative sample.

PMID- 25616919
TI  - Double-blind, randomized, prospective comparison of loading doses of 600 mg
      clopidogrel versus 60 mg prasugrel in patients with acute ST-segment elevation
      myocardial infarction scheduled for primary percutaneous intervention: the ETAMI
      trial (early thienopyridine treatment to improve primary PCI in patients with
      acute myocardial infarction).
AB  - OBJECTIVES: This study compared the timing of onset of antiplatelet action after
      treatment with clopidogrel and prasugrel at first medical contact in patients
      with ST-segment elevation myocardial infarction (STEMI) scheduled for primary
      percutaneous coronary intervention (PPCI). BACKGROUND: Little is known about the
      timing of onset of antiplatelet action after a pre-percutaneous coronary
      intervention (PCI) loading dose of clopidogrel or prasugrel in patients with
      STEMI. METHODS: This double-blind, prospective study randomized 62 patients with
      STEMI scheduled for PPCI in the ambulance or the emergency department to 60 mg
      prasugrel (n = 31) or 600 mg clopidogrel (n = 31). The primary endpoint was the
      platelet reactivity index (PRI) measured with the vasodilator-stimulated
      phosphoprotein assay 2 h after intake of the study medication. Secondary
      endpoints were PRI after 4 h, TIMI (Thrombolysis In Myocardial Infarction)
      patency of the infarct-related artery before and after PCI, and clinical events
      until day 30. RESULTS: The PRI after 2 h (50.4 +/- 32.7% vs. 66.3 +/- 22.2%; p =
      0.035) and after 4 h (39.1 +/- 27.5% vs. 54.5 +/- 49.3%; p = 0.038) were
      significantly lower with prasugrel compared with clopidogrel. In addition, the
      rate of patients with a PRI <50% tended to be higher with prasugrel compared with
      clopidogrel after 2 h (46.7% vs. 28.6%; p = 0.15) and after 4 h (63.0% vs. 38.9%;
      p = 0.06). There were no significant differences in TIMI 2/3 patency before PCI
      (39.2% vs. 31.0%; p = 0.43) and TIMI 3 patency after PCI (88.5% vs. 89.3%; p =
      0.92). CONCLUSIONS: The pre-PCI administration of prasugrel in patients with
      STEMI undergoing PPCI was associated with a significant faster platelet
      inhibition compared with clopidogrel. Therefore, prasugrel should be preferred to
      clopidogrel in this setting. (ETAMI-Study: Early Thienopyridine Treatment to
      Improve Primary PCI in Patients With Acute Myocardial Infarction; NCT01327534).

PMID- 25616921
TI  - Anticoagulation after anterior myocardial infarction: primum non nocere, or first
      do no harm.

PMID- 25616920
TI  - Prophylactic warfarin therapy after primary percutaneous coronary intervention
      for anterior ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: This study sought to determine the benefits of adding oral
      anticoagulation therapy in patients with anterior wall ST-segment elevation
      myocardial infarction (STEMI) patients after primary percutaneous coronary
      intervention (PCI). BACKGROUND: Guidelines suggest adding oral anticoagulation to
      dual-antiplatelet therapy in patients with STEMI when left ventricular apical
      akinesis or dyskinesis is present to prevent thromboembolic complications. The
      benefits of this triple therapy remain unknown. METHODS: We identified patients
      with anterior STEMI referred (PCI) between July 2004 and June 2010 with apical
      akinesis or dyskinesis on transthoracic echocardiography. We compared patients
      who were prescribed warfarin to patients who were not. We excluded patients with
      left ventricular thrombus, a separate need for oral anticoagulation, and previous
      intracranial bleeding. The primary outcome was a composite of net adverse
      clinical events (NACE) consisting of all-cause mortality, stroke, reinfarction,
      and major bleeding at 180 days. RESULTS: Among 460 patients who qualified, 131
      were discharged on warfarin therapy and 329 without warfarin therapy. Dual
      antiplatelet therapy was prescribed for 99.2% of the patients in the warfarin
      group and for 97.6% of the patients in the no warfarin group (p = 0.46). Compared
      with patients in the no warfarin group, patients in the warfarin group had higher
      rates of NACE (14.7% vs. 4.6%, p = 0.001), death (5.4% vs. 1.5%, p = 0.04),
      stroke (3.1% vs. 0.3%, p = 0.02), and major bleeding (8.5% vs. 1.8%, p < 0.0001).
      By propensity score analysis, allocation to warfarin therapy was an independent
      predictor of NACE (odds ratio [OR]: 4.01, 95% confidence interval: 2.15 to 7.50,
      p < 0.0001). In a separate multivariable analysis, the OR of NACE remained
      significantly higher compared with patients who were not prescribed warfarin (OR:
      3.13, 95% confidence interval: 1.34 to 7.22, p = 0.007). CONCLUSIONS: Our results
      do not support the addition of warfarin therapy after primary PCI in patients
      with apical akinesis or dyskinesis.

PMID- 25616922
TI  - Relationship between time to invasive assessment and clinical outcomes of
      patients undergoing an early invasive strategy after fibrinolysis for ST-segment
      elevation myocardial infarction: a patient-level analysis of the randomized early
      routine invasive clinical trials.
AB  - OBJECTIVES: This study investigated the relationship between time to invasive
      assessment and outcomes among ST-segment elevation myocardial infarction patients
      randomized to early angiography after fibrinolysis. BACKGROUND: The optimal
      timing of coronary angiography after fibrinolysis and the association with
      clinical outcomes is uncertain. METHODS: Patient-level data from 6 randomized
      trials, with a median time to angiography <12 h after fibrinolysis, were pooled.
      The primary endpoint was 30-day death or reinfarction. The key secondary endpoint
      was in-hospital major bleeding. The relationship between fibrinolysis to
      angiography time and symptom onset to angiography time with outcomes was studied
      using 2- and 4-h intervals, respectively, and in multivariable models. RESULTS:
      Among 1,238 patients, the median fibrinolysis to angiography time was 165 min,
      and the median symptom onset to angiography time was 5.33 h. The primary and key
      secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints
      did not vary significantly with increasing fibrinolysis to angiography time.
      Early angiography (<2 h) after fibrinolysis was not associated with increased
      bleeding. Recurrent ischemia increased with increasing fibrinolysis to
      angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year
      death/reinfarction and 30-day recurrent ischemia increased significantly with
      increasing symptom onset to angiography time. Neither fibrinolysis to angiography
      time nor symptom onset to angiography time was an independent predictor of the
      primary endpoint. Only symptom onset to angiography time was an independent
      predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence
      interval: 1.02 to 1.12, p = 0.01). CONCLUSIONS: Very early angiography (<2 h)
      after fibrinolysis was not associated with an increased risk of 30-day
      death/reinfarction or in-hospital major bleeding, and angiography within 4 h
      after fibrinolysis was associated with reduced 30-day recurrent ischemia. A
      shorter symptom onset to angiography time (<4 h) was associated with reduced 30
      day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current
      environment of regional networks of 24/7 primary percutaneous coronary
      intervention (PCI) centers, the clinical implication of these findings is that
      patients initially treated with fibrinolysis should also be promptly transferred
      to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous
      Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST
      Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182).

PMID- 25616923
TI  - Beyond the guidelines stance: green light for very early angiography after
      fibrinolysis.

PMID- 25616924
TI  - Absorb bioresorbable vascular scaffold versus everolimus-eluting metallic stent
      in ST-segment elevation myocardial infarction: 1-year results of a propensity
      score matching comparison: the BVS-EXAMINATION Study (bioresorbable vascular
      scaffold-a clinical evaluation of everolimus eluting coronary stents in the
      treatment of patients with ST-segment elevation myocardial infarction).
AB  - OBJECTIVES: The purpose of this study was to compare the 1-year outcome between
      bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic stent (EES)
      in ST-segment elevation myocardial infarction (STEMI) patients. BACKGROUND: The
      Absorb BVS (Abbott Vascular, Santa Clara, California) is a polymeric scaffold
      approved for treatment of stable coronary lesions. Limited and not randomized
      data are available on its use in ST-segment elevation myocardial infarction
      (STEMI) patients. METHODS: This study included 290 consecutive STEMI patients
      treated by BVS, compared with either 290 STEMI patients treated with EES or 290
      STEMI patients treated with bare-metal stents (BMS) from the EXAMINATION (A
      Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of
      Patients With ST-segment Elevation Myocardial Infarction) trial, by applying
      propensity score matching. The primary endpoint was a device-oriented endpoint
      (DOCE), including cardiac death, target vessel myocardial infarction, and target
      lesion revascularization, at 1-year follow-up. Device thrombosis, according to
      the Academic Research Consortium criteria, was also evaluated. RESULTS: The
      cumulative incidence of DOCE did not differ between the BVS and EES or BMS groups
      either at 30 days (3.1% vs. 2.4%, hazard ratio [HR]: 1.31 [95% confidence
      interval (CI): 0.48 to 3.52], p = 0.593; vs. 2.8%, HR: 1.15 [95% CI: 0.44 to
      2.30], p = 0.776, respectively) or at 1 year (4.1% vs. 4.1%, HR: 0.99 [95% CI:
      0.23 to 4.32], p = 0.994; vs. 5.9%, HR: 0.50 [95% CI: 0.13 to 1.88], p = 0.306,
      respectively). Definite/probable BVS thrombosis rate was numerically higher
      either at 30 days (2.1% vs. 0.3%, p = 0.059; vs. 1.0%, p = 0.324, respectively)
      or at 1 year (2.4% vs. 1.4%, p = 0.948; vs. 1.7%, p = 0.825, respectively), as
      compared with EES or BMS. CONCLUSIONS: At 1-year follow-up, STEMI patients
      treated with BVS showed similar rates of DOCE compared with STEMI patients
      treated with EES or BMS, although rate of scaffolds thrombosis, mostly clustered
      in the early phase, was not negligible. Larger studies with longer follow-up are
      needed to confirm our findings.

PMID- 25616925
TI  - Bioresorbable drug-eluting stents: an immature technology in need of mature
      application.

PMID- 25616926
TI  - Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin
      with or without routine glycoprotein IIb/IIIa inhibitors in patients with acute
      coronary syndrome.
AB  - OBJECTIVES: The aim of this meta-analysis was to compare the 30-day safety and
      efficacy of bivalirudin with those of heparin with or without routine
      administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute
      coronary syndrome (ACS). BACKGROUND: Bivalirudin has been a mainstay of
      anticoagulation in patients with ACS compared with heparin. The extent to which
      trial results have been affected by the coadministration of heparin with a GPI,
      however, remains unclear. METHODS: A total of 13 randomized, controlled trials
      involving 24,605 patients were included. RESULTS: There was no significant
      difference in 30-day mortality or myocardial infarction rate with bivalirudin
      compared with heparin with or without routine GPI administration. A reduction of
      30-day major bleeding was observed with bivalirudin compared with heparin that
      was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95%
      confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally
      administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of
      stent thrombosis (ST) at 30 days was significantly increased with bivalirudin
      compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to
      2.45, p = 0.02), but not compared with heparin plus provisionally administered
      GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (<= 24 h),
      however, was almost 4.5-fold higher with bivalirudin compared with heparin with
      or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ
      significantly. CONCLUSIONS: Overall, bivalirudin in ACS patients is associated
      with a significant reduction of major bleeding compared with heparin plus
      routinely administered GPI, but with a marked increase in ST rates compared with
      heparin with or without GPI.

PMID- 25616927
TI  - Acute stent thrombosis after primary percutaneous coronary intervention: insights
      from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography).
AB  - OBJECTIVES: This study sought to determine clinical, procedural, and treatment
      factors associated with acute stent thrombosis (AST) in the EUROMAX (European
      Ambulance Acute Coronary Syndrome Angiography) trial. BACKGROUND: Bivalirudin
      started during transport for primary percutaneous coronary intervention (PCI) for
      ST-segment elevation myocardial infarction significantly reduced major bleeding
      compared with heparin with or without glycoprotein IIb/IIIa inhibitors (GPI), but
      it was associated with an increase in AST. METHODS: We compared patients with (n
      = 12) or without AST (n = 2,184) regarding baseline, clinical, and procedural
      characteristics and antithrombotic treatment strategies (choice of P2Y12
      inhibitor, post-primary PCI bivalirudin infusion dose [0.25 mg/kg/h, or BIV-LOW]
      vs. [1.75 mg/kg/h, or BIV-PCI] vs. heparin +/- GPI). Logistic regression was
      performed to identify independent correlates of AST. RESULTS: The overall AST
      rate was 0.6% and was higher with bivalirudin than with heparin +/- GPI (1.1% vs.
      0.2%; p = 0.007). Median time to AST was 2.3 h (interquartile range: 1.9 to 2.8
      h). Patients with AST had less hypertension (2 of 14 [14.0%] vs. 961 of 2,182
      [44.0%]; p = 0.03), and more frequently received GPI (11 of 14 [78.6%] vs. 880 of
      2,183 [40.3%]; p = 0.004). Multivariate analysis using Firth penalized maximum
      likelihood estimation found hypertension (odds ratio [OR]: 0.24, 95% confidence
      interval [CI]: 0.07 to 0.92; p = 0.037) and BIV-LOW (OR: 5.8, 95% CI: 1.5 to
      22.2; p = 0.010) predictive of AST. Choice of P2Y12 inhibitor had no impact on
      AST. Compared with heparin +/- GPI, AST rates were higher for BIV-LOW (11 of 670
      [1.6%] vs. 2 of 947 [0.2%]; p = 0.008), but not different for BIV-PCI (1 of 244
      [0.4%]; p = 0.588). CONCLUSIONS: In this post-hoc analysis from EUROMAX, AST
      occurred very early and was not mitigated by the novel P2Y12 inhibitors.
      Prolonging the bivalirudin infusion at the PCI dose (but not at a lower dose)
      appeared to mitigate the risk of AST.

PMID- 25616928
TI  - Heparin may be hard to beat: however much you are willing to spend on
      bivalirudin.

PMID- 25616929
TI  - Is heparin an acceptable anticoagulant when glycoprotein IIb/IIIa inhibitors are
      not used?

PMID- 25616930
TI  - Follow the data: bivalirudin (and not heparin alone) during percutaneous coronary
      intervention provides the best clinical outcomes.

PMID- 25616931
TI  - A focus on ST-segment elevation myocardial infarction.

PMID- 25616932
TI  - Genetic fidelity assessment in micropropagated plants using cytogenetical
      analysis and heterochromatin distribution: a case study with Nepenthes khasiana
      Hook f.
AB  - Rapid clonal propagation of selected genotypes has been one of the most
      extensively exploited approaches of biotechnology. However, inclusion of
      somaclonal variations in tissue-culture-derived plants results in the production
      of undesirable plant off-types which limits its applications in tissue culture
      industry. Therefore, the most critical concern has been the maintenance of
      genetic uniformity of micropropagated plants. Assessment of genetic fidelity in
      tissue-culture-raised plants of three consecutive regenerations of Nepenthes
      khasiana has been successfully carried out using chromosome counts and
      heterochromatin distribution pattern wherein changes in the number of chromosomes
      and the distribution of AT and GC base pairs were recorded. The cells studied in
      the plantlets of the first regeneration (23.33 %) showed deviant number of
      chromosome which was increased to 33.33 % and 40 % in the plantlets of the second
      and the third regenerations, respectively. Also, 4',6-diamidino-2-phenylindole
      (DAPI)(+) and chromomycin A3 (CMA)(+) binding sites, on an average of 5.74 +/-
      0.47 and 5.00 +/- 0.30, were observed in the plantlets of the first regeneration.
      Subsequently, DAPI(+) binding sites were increased to 6.61 +/- 0.39 and 6.74 +/-
      0.57 in the plantlets of the second and the third regenerations, respectively,
      with a corresponding decrease in the CMA(+) binding sites (4.63 +/- 0.45 and 4.16
      +/- 0.47 CMA(+) sites in the plantlets of the second and the third regenerations,
      respectively). The study reveals an increase in cytological variations in the
      morphologically similar micropropagated plants of N. khasiana with the subsequent
      regenerations which further necessitate the determination of genetic integrity of
      micropropagated plants.

PMID- 25616933
TI  - Postural stability during the transition from double-leg stance to single-leg
      stance in anterior cruciate ligament injured subjects.
AB  - BACKGROUND: An anterior cruciate ligament injury may lead to deteriorations in
      postural stability. The goal of this study was to evaluate postural stability
      during the transition from double-leg stance to single-leg stance of both legs in
      anterior cruciate ligament injured subjects and non-injured control subjects with
      a standardized methodology. METHODS: Fifteen control subjects and 15 anterior
      cruciate ligament injured subjects (time after injury: mean (SD)=1.4 (0.7)
      months) participated in the study. Both groups were similar for age, gender,
      height, weight and body mass index. Spatiotemporal center of pressure outcomes of
      both legs of each subject were measured during the transition from double-leg
      stance to single-leg stance in eyes open and eyes closed conditions. Movement
      speed was standardized. FINDINGS: The center of pressure displacement after a new
      stability point was reached during the single-leg stance phase was significantly
      increased in the anterior cruciate ligament injured group compared to the control
      group in the eyes closed condition (P<.001). No significant different postural
      stability outcomes were found between both legs within both groups (P>.05). No
      significant differences were found during the transition itself (P>.05).
      INTERPRETATION: The anterior cruciate ligament injured group showed postural
      stability deficits during the single-leg stance phase compared to the non-injured
      control group in the eyes closed condition. Using the non-injured leg as a normal
      reference when evaluating postural stability of the injured leg may lead to
      misinterpretations, as no significant differences were found between the injured
      and non-injured leg of the anterior cruciate ligament injured group.

PMID- 25616934
TI  - Integrating docking and molecular dynamics approaches for a series of proline
      based 2,5-diketopiperazines as novel alphabeta-tubulin inhibitors.
AB  - In this work, docking tools were utilized in order to study the binding
      properties of more than five hundred of proline-based 2,5-diketopiperazine in the
      binding site of alphabeta-tubulin. Results revealed that 20 compounds among them
      showed lower binding energies in comparison with Tryprostatin-A, a well known
      tubulin inhibitor and therefore could be potential inhibitors of tubulin.
      However, the precise evaluation of binding poses represents the similar binding
      modes for all of these compounds and Tryprostatin-A. Finally, the best docked
      complex was subjected to a 25 ns molecular dynamics simulation to further
      validate the proposed binding mode of this compound. 

PMID- 25616936
TI  - Sustained Effects of a Neural-based Intervention in a Refractory Case of Tourette
      Syndrome.

PMID- 25616937
TI  - Commentary on "can we improve the morbidity and mortality associated with the
      associating liver partition with portal vein ligation for staged hepatectomy
      (ALPPS) procedure in the management of colorectal liver metastases?".

PMID- 25616938
TI  - Implication of an extremely high preoperative alpha-fetoprotein value (>4,000
      ng/mL) for the long-term outcomes of hepatectomy for resectable hepatocellular
      carcinoma.
AB  - BACKGROUND: The implication of extremely high preoperative alpha-fetoprotein
      (AFP) values for the long-term outcomes of hepatectomy for resectable
      hepatocellular carcinoma (HCC) remains uncertain. METHODS: A total of 762
      hepatectomized HCC patients were divided into 3 groups according to preoperative
      AFP serum concentrations: 578 patients with AFP <100 ng/mL (low [LAP]), 147
      patients with AFP 100-4,000 ng/mL (high [HAP]), and 37 patients with AFP >=4,000
      ng/mL (extremely high [EAP]). The clinicopathologic features and prognosis of the
      EAP group were compared with those of the other 2 groups to investigate their
      characteristics and whether the choice of hepatectomy was valid. RESULTS: The EAP
      group had a greater proportion of younger patients and those with hepatitis B
      compared with the other 2 groups. Large tumor size, poor histologic
      differentiation, and microscopic vascular invasion were also more common in the
      EAP group. The recurrence-free and overall survival rates of the EAP group were
      worse than those of the LAP group (both P < .01) but were not greatly different
      from those of the HAP group (P = .65 and P = .80, respectively). When the
      analysis was limited to solitary HCC cases, both recurrence-free and overall
      survival rates of EAP were not significantly different from those of LAP (P = .79
      and P = .99, respectively). CONCLUSION: An extremely high AFP level does not
      provide additional postoperative prognostic implications beyond those provided by
      a high AFP level. Hepatectomy should be performed without reservation for cases
      of HCC associated with an extremely high AFP value.

PMID- 25616939
TI  - Hospital readmissions after liver surgery for metastatic colorectal cancer.
AB  - BACKGROUND: Hospital readmission rates after surgery are increasingly used as a
      measure of quality of care. Numerous efforts to decrease these rates have been
      established by care providers and insurance companies. There is sparse
      information available regarding readmission rates after liver resection for
      metastatic colorectal cancer (mCRC). METHODS: Data from hospital readmissions
      occurring within 30 days after liver resection and/or open ablation for mCRC
      between 2005 and 2010 were captured from the urgent care center (emergency room)
      database and were compared with data from the institutional database.
      Complications during the primary stay and those leading to readmission were
      analyzed and graded with an established scoring system. The time course of
      complications and their therapeutic management were analyzed as well. RESULTS: Of
      746 patients who underwent surgery during this period, 277 (37%) developed
      medical or surgical complications within 30 days, and 97 (13%) required
      readmission after discharge. The most common causes for readmission were
      perihepatic or intra-abdominal collections (40%), wound issues (13%), and
      gastrointestinal issues (12%). Forty-four patients had complications grade 3 or
      higher during readmission, thus representing 34% of all major complications
      (grade 3 or higher). Seventy-four readmitted patients (27% of all patients with
      complications) had a complication of lesser grade during their primary stay. The
      median postoperative day of readmission was 15 (range, 6-30) with wide variation
      among complication types. CONCLUSION: Readmission is common after liver resection
      and/or ablation for mCRC. One quarter of patients who develop complications
      postoperatively will have their most significant complication as an outpatient
      and require rehospitalization.

PMID- 25616940
TI  - Time interval to recurrence as a predictor of overall survival in salvage liver
      transplantation for patients with hepatocellular carcinoma associated with
      hepatitis B virus.
AB  - BACKGROUND: Salvage liver transplantation (SLT) has been proposed for recurrent
      hepatocellular carcinoma (HCC) after hepatectomy; however, it is unclear how the
      time interval to tumor recurrence from previous hepatectomy affects prognosis.
      METHODS: We analyzed retrospectively the outcomes of 62 patients who underwent
      SLT in the Liver Transplantation Center of the First Affiliated Hospital of
      Zhejiang University between 2001 and 2012. SLT recipients were divided into 2
      groups based on whether the time interval to recurrence was >1 year (L group) or
      <1 year (S group). RESULTS: Baseline characteristics were similar between the 2
      groups. The 1-, 3-, and 5-year overall survival rates were 81%, 45%, and 45% in
      the L group, which were better than in the S group, with 47%, 21%, and 21%,
      respectively (P = .005). The corresponding tumor-free survival rates were similar
      (P = .60) between 2 groups, with 71%, 51%, and 41% in the L group versus 55%,
      55%, and 55% in the S group. Macrovascular invasion (hazard ratio [HR], 3.30),
      greatest tumor diameter (HR, 3.92), and time interval to tumor recurrence from
      previous hepatectomy (HR, 0.29) were independent predictors for overall survival.
      Furthermore, the diameter of the largest tumor was the only independent predictor
      of tumor-free survival (HR, 25.64). CONCLUSION: The time interval to HCC
      recurrence from a previous hepatectomy is an important factor associated with
      survival after SLT. This finding should be helpful in guiding patient selection
      criteria for SLT in patients with previous hepatectomy.

PMID- 25616935
TI  - Nutritional adequacy according to carbohydrates and fat quality.
AB  - PURPOSE: To investigate the association between carbohydrate quality, fat quality
      or adherence to the Mediterranean diet and intake adequacy of 19 micronutrients
      in the PREDIMED (PREvencion con DIeta MEDiterranea) trial, a multicenter,
      randomized, controlled, parallel group and primary prevention trial conducted in
      Spain. METHODS: We assessed baseline dietary intake of 6,542 elderly subjects at
      high cardiovascular risk through a validated food frequency questionnaire (FFQ)
      and a validated 14-item Mediterranean diet (Med-diet) score. We used a
      multidimensional carbohydrate quality index (CQI) using four criteria and a fat
      quality index (FQI) according to the ratio (MUFA + PUFA)/(SFA + TFA). The
      probability of intake adequacy was calculated comparing the intakes to DRI, and
      also using the probabilistic approach. Absolute and adjusted probability of
      having inadequate intake for either >=6 DRI or >=8 DRI were estimated to assess
      nutritional adequacy according to quintiles of each index. RESULTS: The lowest
      prevalence of inadequate micronutrient intake (>=8 DRI) was found in the highest
      quintile of CQI or Med-diet score, and in the lowest quintile of FQI (adjusted
      fold risk: 1.4, 3.4 and 10.2 respectively in comparison with the lowest
      quintile). P for trend <0.001 in three multivariable models. A higher CQI or Med
      Diet score and a lower FQI were significantly associated with a lower fold risk
      of unmet EAR values. CONCLUSIONS: A multidimensional assessment of CQI can be a
      useful tool to evaluate the quality of carbohydrates. This score and a 14-item
      Med-diet score were positively related to overall micronutrient adequacy in
      elderly participants.

PMID- 25616941
TI  - Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before
      liver resection when using intermittent vascular inflow occlusion: a randomized
      clinical trial.
AB  - BACKGROUND: Ischemic preconditioning (IPC) and anesthetic preconditioning (APC)
      have been reported to attenuate ischemia-reperfusion (IR) injury after liver
      resection under continuous inflow occlusion. This study evaluates whether these
      strategies enhance hepatic protection of remnant liver against IR after liver
      resection with intermittent clamping (INT). METHODS: A total of 106 patients
      without underlying liver disease and submitted to liver resection using INT were
      randomized into 3 groups: IPC (10 minutes of inflow occlusion followed by 10
      minutes of reperfusion before liver transection), APC (sevoflurane administration
      for 20 minutes before liver transection), and INT (no preconditioning). Patients
      were also stratified according to the extent of the hepatectomy. Cytoprotection
      was evaluated by comparing hepatocyte and endothelial dysfunction markers,
      apoptosis, histologic lesions, and postoperative outcome. RESULTS: No differences
      were observed in preoperative chemotherapy and steatosis, total warm ischemia
      time, operative time, or blood loss. Kinetics of transaminases (aspartate
      aminotransferase, P = .137; alanine aminotransferase, P = .616), bilirubin (P =
      .980), and hyaluronic acid increase (P = .514) revealed no differences.
      Significant apoptosis was present in 40% of patients, mild-to-moderate leukocyte
      infiltration and steatosis in 45% and 55%, respectively, and mild sinusoidal
      congestion in 65%, with a similar distribution in the 3 groups. When patients
      were stratified by major versus minor resections, no differences were observed in
      any of the variables studied. Postoperative clinical outcomes were also similar.
      CONCLUSION: These results suggest that these protocols of IPC and APC used in
      this study do not provide better cytoprotection from IR when INT is used.

PMID- 25616943
TI  - Watchful waiting in incisional hernia: is it safe?
AB  - BACKGROUND: Incisional hernia (IH) is among the most common postoperative
      complications after abdominal surgery. Operative treatment (OT) using mesh is the
      treatment of choice. A strategy of watchful waiting (WW) might be a considered in
      some patients. This retrospective study compares the outcomes of WW and OT.
      METHODS: All patients presenting with IH in an academic surgery department
      between January 2004 and December 2009 were analyzed according to whether they
      were treated by WW or OT. Crossovers between both groups were also analyzed.
      Patient characteristics, information about the initial abdominal operative
      procedure, symptoms at presentation, and characteristics of the hernia were
      collected retrospectively. In case of OT, postoperative complications were
      analyzed. RESULT: In total, 255 patients were included; 151 (59%) in the OT group
      and 104 (41%) in WW group. The median follow-up was 68 months (interquartile
      range [IQR], 52-93). The reasons for WW were the absence of symptoms in 34
      patients (33%), comorbidities in 24 (23%), and obesity in 23 (22%). During follow
      up, 34 patients (33%) crossed over from WW to OT. Eight of the crossovers (24%)
      were emergency repairs owing to incarceration at a median of 1 month (IQR, 1-5)
      after the start of WW. The incidence of unexpected intraoperative intestinal
      perforation was greater in the crossover group (13%) compared with the OT group
      (2%; P = .002). Postoperative fistulas were seen in 7% of patients who crossed
      over from WW to OT versus 0% in primary OT (P = .002). Postoperatively, 3
      patients died, 2 of whom were treated operatively after belonging initially to
      the WW group. CONCLUSION: WW for IH leads to high crossover rates with
      significantly greater incidence of intraoperative perforations, fistulas, and
      mortality, than in the OT group, particularly in patients who require emergency
      repair of IH owing to incarceration.

PMID- 25616942
TI  - Survival in ampullary cancer: potential role of different KRAS mutations.
AB  - OBJECTIVE: The prognosis of ampullary adenocarcinoma (AA) usually is favorable;
      however, a subset of AA have poor biology and outcomes similar to pancreatic
      cancer. Patients in this subset will have early recurrence and death usually
      within 2 years. To date, there are no genetic markers to identify these patients.
      This study identifies the high-risk subset of AA and evaluates the mutational
      status of KRAS in predicting poor outcome. METHODS: The tumor registry of an
      academic center was reviewed for data on patients managed operatively with AA.
      KRAS genotypes were determined for these patients using a polymerase chain
      reaction-based assay on clinical specimens. Analysis of variance and chi(2) tests
      was used to categorize continuous and categorical variables. Univariate and
      multivariate survival analyses were performed using Kaplan-Meier and Cox methods,
      respectively. RESULTS: A total of 146 patients were identified with AA between
      1982 and 2008. After stringent pathologic review, 97 patients were confirmed with
      AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed
      67% were wild-type (KRAS(WT)), and 33% were mutant for KRAS. Patients with
      KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median
      survival (62 months) compared with those with KRAS(non-G12D) mutants (median
      survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P =
      .05). Patients with survival <=30 months were labeled "high-risk." Of the 9
      patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of
      KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with
      KRAS(G12D) also were more likely to present with advanced T stage. CONCLUSION:
      The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses
      and may be used to identify patients at risk of early recurrence and poorer
      survival who may benefit from adjuvant therapy.

PMID- 25616944
TI  - Pain control with ultrasound-guided inguinal field block compared with spinal
      anesthesia after hernia surgery: a randomized trial.
AB  - BACKGROUND: Inguinal field block (IFB) is a recommended technique for pain
      control after inguinal hernia repair but is also underused by surgeons.
      Currently, there is no decisive evidence on which technique, IFB or spinal
      anesthesia block (SAB), provides better pain control during the first day after
      hernia repair. In this study, we compared ultrasound-guided IFB performed by
      anesthesiologists and SAB for pain control during the first day after hernia
      repair. METHODS: We compared static and dynamic pain scores measured with a
      numerical rating scale in 86 male patients scheduled for elective unilateral
      inguinal hernia repair with either ultrasound-guided IFB (n = 42) or SAB (n =
      44). RESULTS: Dynamic and static pain at 4 hours (P < .01, r > 0.34, "large
      effect size"), and dynamic pain the morning after operation (P = .04, r > 0.20,
      "medium effect size") were less in the field block group compared with the SAB
      group. Postoperative analgesic consumption was reduced during hospital stay (P =
      .005, r > 0.34, "large effect size") and for 7 postoperative days in the field
      block group (P = .03, r > 0.20, "medium effect size"). CONCLUSION: In this study,
      ultrasound-guided IFB provided lesser dynamic pain scores during the first
      postoperative day and reduced use of analgesics for 1 week compared with spinal
      anesthesia after inguinal hernia repair. Our technique could become a substitute
      performed by anesthesiologists in settings in which IFB is not performed
      routinely by surgeons.

PMID- 25616945
TI  - The collagen turnover profile is altered in patients with inguinal and incisional
      hernia.
AB  - BACKGROUND: Disturbed metabolism in the extracellular matrix (ECM) contributes to
      formation of abdominal wall hernias. The aim of this study was to gain deeper
      insight into the ECM turnover in hernia patients by analyzing serum biomarkers
      specifically reflecting collagen synthesis and breakdown in the interstitial
      matrix (types I, III, and V collagens) and in the basement membrane (type IV
      collagen). MATERIAL AND METHODS: Patients with 3 different types of hernias were
      included: Primary unilateral inguinal hernia (n = 17), multiple hernias defined
      as >=3 hernias (n = 21), and incisional hernia (n = 25). Patients without hernias
      scheduled to undergo elective operation for gallstones (n = 18) served as
      controls. Whole venous blood was collected preoperatively. Biomarkers for
      synthesis of interstitial matrix (PINP, Pro-C3, P5CP) and basement membrane
      (P4NP) as well as corresponding degradation (C1M, C3M, C5M, and C4M) were
      measured in serum by validated, solid-phase competitive assays. RESULTS: In
      inguinal hernia patients, the turnover of the interstitial matrix collagens type
      III (P < .042) and V (P < .001) was decreased compared with controls, whereas the
      turnover of the basement membrane collagen type IV was increased (P < .001). In
      incisional hernia patients, the turnover of type V collagen was decreased (P =
      .048) and the turnover of type IV collagen was increased compared with the hernia
      free controls (P < .001). CONCLUSION: Hernia patients demonstrated systemically
      altered collagen metabolism. The serologic turnover profile of type IV collagens
      may predict the presence of inguinal and incisional hernia. Regulation of type IV
      collagen turnover may be crucial for hernia development.

PMID- 25616947
TI  - The current status and management of blunt adrenal gland trauma.
AB  - BACKGROUND: Blunt adrenal gland trauma (BAGT) is a potentially devastating event
      if unrecognized during the treatment course of patients with trauma. Because of
      its rarity, no current algorithm or consensus exists for BAGT. In the present
      study, we demonstrated the feasibility and safety of transcatheter angiographic
      embolization (TAE) in BAGT and analyzed the clinical presentation and outcome of
      BAGT. METHODS: We conducted a prospective collection and retrospective review at
      a level I trauma center in Taiwan. This study included all of the patients that
      sustained BAGT from May 2004 to May 2013. We retrieved and analyzed the patient
      demographic data, clinical presentation, BAGT grade, injury severity score,
      management, hospital stay, and mortality. RESULTS: The cohort consisted of 77
      patients: 59 men and 18 women. The mean age was 34.3 +/- 15.5 years. The right
      side was the predominant site of injury (59/77; 76.6%). Six patients underwent
      operation; 18 patients underwent angiography, including four TAEs, and the
      remaining patients underwent conservative management. The mortality rate was 9.1%
      (7/77), and a high injury severity score was an independent factor to predict
      mortality. CONCLUSION: In conclusion, BAGT is a rare injury with a benign
      prognosis. Most patients can be treated conservatively. Furthermore, this study
      demonstrates that both TAE and operation can be used to achieve hemostasis. The
      mortality of BAGT was related to severe associated injuries. BAGT is an indicator
      of severe multiple trauma; however, it does not increase mortality or prolong
      hospital stay.

PMID- 25616946
TI  - Gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia
      virus GLV-1h153 for management of colorectal peritoneal carcinomatosis.
AB  - BACKGROUND: Peritoneal carcinomatosis (PC) is a terminal progression of
      colorectal cancer (CRC). Poor response to cytoreductive operation and
      chemotherapy coupled with the inability to reliably track disease progression by
      the use of established diagnostic methods, make this a deadly disease. We
      examined the effectiveness of the oncolytic vaccinia virus GLV-1h153 as a
      therapeutic and diagnostic vehicle. We believe that viral expression of the human
      sodium iodide transporter (hNIS) provides both real-time monitoring of viral
      therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC).
      METHODS: Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was
      assayed in vitro. Viral replication was examined by standard viral plaque assays.
      Orthotopic CRPC xenografts were generated in athymic nude mice and subsequently
      administered GLV-1h153 intraperitoneally. A decrease in tumor burden was assessed
      by mass. Orthotopic tumors were visualized by single-photon emission computed
      tomography/computed tomography after Iodine ((131)I) administration and by
      fluorescence optical imaging. RESULTS: GLV-1h153 infected and killed CRC cells in
      a time- and concentration-dependent manner. Viral replication demonstrated
      greater than a 2.35 log increase in titer over 4 days. Intraperitoneal treatment
      of orthotopic CRPC xenografts resulted in a substantial decrease in tumor burden.
      Infection of orthotopic xenografts was therapeutic and facilitated monitoring by
      (131)I-single-photon emission computed tomography/computed tomography via
      expression of hNIS in infected tissue. CONCLUSION: GLV-1h153 kills CRC in vitro
      effectively and decreases tumor burden in vivo. We demonstrate that GLV-1h153 can
      be used as an agent to provide accurate delineation of tumor burden in vivo.
      These findings indicate that GLV-1h153 has potential for use as a therapeutic and
      diagnostic agent in the treatment of CRPC.

PMID- 25616948
TI  - Hypocalcaemia after total thyroidectomy: could intact parathyroid hormone be a
      predictive factor for transient postoperative hypocalcemia?
AB  - BACKGROUND: Hypocalcemia, the most common complication of thyroidectomy, is a
      transient condition in up to 27% of patients and a permanent condition
      approximately 1% of patients. The aim of this prospective study was to evaluate
      reliability of postoperative intact parathyroid hormone (iPTH) assessment for
      predicting clinically relevant postthyroidectomy hypocalcemia for a safe early
      discharge of patients with no overtreatment. METHODS: Seventy-five consecutive
      patients (age 51 +/- 13 years [mean +/- SD]) undergoing total or completion
      thyroidectomy with no concomitant parathyroid diseases or renal failure were
      included in the present study. Serum iPTH level was determined before and 2 hours
      after thyroidectomy. Serum calcium concentration was determined 1 day before and
      2 days postoperatively. RESULTS: The occurrence of postoperative hypocalcemia was
      correlated both with the absolute and relative iPTH decrease, determined as a
      ratio of the preoperative value (P < .0001). There was a greater difference in
      relative decrease in iPTH between patients remaining normocalcemic and those with
      hypocalcemia present on the second postoperative day. Hypocalcemic patients on
      the second postoperative day had a 62% relative decrease in iPTH 2 hours after
      thyroidectomy. CONCLUSION: The relative decrease in serum iPTH was greater in
      patients with hypocalcemia arising on the second postoperative day rather than in
      patients who remained normocalcemic. The relative decrease in iPTH determined 2
      hours after total thyroidectomy together with the serum calcium concentration 24
      hours after thyroidectomy proved to be useful predictors of sustained
      hypocalcemia and might change the clinical management of patients after thyroid
      surgery to support a longer hospitalization in these selected patients.

PMID- 25616949
TI  - What to do with thyroid nodules showing benign cytology and BRAF(V600E) mutation?
      A study based on clinical and radiologic features using a highly sensitive
      analytic method.
AB  - BACKGROUND: BRAF(V600E) mutation analysis has been used as a complementary
      diagnostic tool to ultrasonography-guided, fine-needle aspiration (US-FNA) in the
      diagnosis of thyroid nodule with high specificity reported up to 100%. When
      highly sensitive analytic methods are used, however, false-positive results of
      BRAF(V600E) mutation analysis have been reported. In this study, we investigated
      the clinical, US features, and outcome of patients with thyroid nodules with
      benign cytology but positive BRAF(V600E) mutation using highly sensitive analytic
      methods from US-FNA. METHODS: This study included 22 nodules in 22 patients (3
      men, 19 women; mean age, 53 years) with benign cytology but positive BRAF(V600E)
      mutation from US-FNA. US features were categorized according to the internal
      components, echogenicity, margin, calcifications, and shape. Suspicious US
      features included markedly hypoechogenicity, noncircumscribed margins, micro or
      mixed calcifications, and nonparallel shape. Nodules were considered to have
      either concordant or discordant US features to benign cytology. Medical records
      and imaging studies were reviewed for final cytopathology results and outcomes
      during follow-up. RESULTS: Among the 22 nodules, 17 nodules were reviewed.
      Fifteen of 17 nodules were malignant, and 2 were benign. The benign nodules were
      confirmed as adenomatous hyperplasia with underlying lymphocytic thyroiditis and
      a fibrotic nodule with dense calcification. Thirteen of the 15 malignant nodules
      had 2 or more suspicious US features, and all 15 nodules were considered to have
      discordant cytology considering suspicious US features. Five nodules had been
      followed with US or US-FNA without resection, and did not show change in size or
      US features on follow-up US examinations. CONCLUSION: BRAF(V600E) mutation
      analysis is a highly sensitive diagnostic tool in the diagnosis of papillary
      thyroid carcinomas. In the management of thyroid nodules with benign cytology but
      positive BRAF(V600E) mutation, thyroidectomy should be considered in nodules
      which have 2 or more suspicious US features and are considered discordant on
      image-cytology correlation.

PMID- 25616950
TI  - Routine clinical markers of the magnitude of the systemic inflammatory response
      after elective operation: a systematic review.
AB  - BACKGROUND: Operative injury to the body from all procedures causes a
      stereotypical cascade of neuroendocrine, cytokine, myeloid, and acute phase
      responses. This response has been examined commonly by the use of cortisol,
      interleukin-6 (IL-6), white cell count, and C-reactive protein (CRP). We aimed to
      determine which markers of the systemic inflammatory response were useful in
      determining the magnitude of injury after elective operations. METHODS: A
      systematic review of the literature was performed using surgery, endocrine
      response, systemic inflammatory response, cortisol, IL-6, white cell count, and
      CRP. For each analyte the studies were grouped according to whether the operative
      injury was considered to be minor, moderate, or major and then by the operative
      procedure. RESULTS: A total of 164 studies were included involving 14,362
      patients. The IL-6 and CRP responses clearly were associated with the magnitude
      of operative injury and the invasiveness of the operative procedure. For example,
      the peak CRP response increased from 52 mg/L with cholecystectomy to 123 mg/L
      with colorectal cancer resection, 145 mg/L with hip replacement, 163 mg/L after
      abdominal aortic aneurysm repair, and 189 mg/L after open cardiac surgery. There
      also appeared to be a difference between minimally invasive/laparoscopic and open
      procedures such as cholecystectomy (27 vs 80 mg/L), colorectal cancer resection
      (97 vs 133 mg/L), and aortic aneurysm repair (132 vs 180 mg/L). CONCLUSION: Peak
      IL-6 and CRP concentrations consistently were associated with the magnitude of
      operative injury and operative procedure. These markers may be useful in the
      objective assessment of which components of Enhanced Recovery after Surgery are
      likely to improve patient outcome and to assess the possible impact of operative
      injury on immune function.

PMID- 25616951
TI  - Clinical registries and quality measurement in surgery: a systematic review.
AB  - BACKGROUND: Surgical clinical registries provide clinical information with the
      intent of measuring and improving quality. This study aimed to describe how
      surgical clinical registries have been used to measure surgical quality, the
      reported findings, and the limitations of registry measurements. METHODS:
      Medline, CINAHL, and Cochrane were queried for English articles with the terms:
      "registry AND surgery AND quality." Eligibility criteria were studies explicitly
      assessing quality measurement with registries as the primary data source. Studies
      were abstracted to identify registries, define registry structure, uses for
      quality measurement, and limitations of the measurements used. RESULTS: A total
      of 111 studies of 18 registries were identified for data abstraction. Two
      registries were financed privately, and 5 registries were financed by a
      governmental organization. Across registries, the most common uses of process
      measures were for monitoring providers and as platforms for quality improvement
      initiatives. The most common uses of outcome measures were to improve quality
      modeling and to identify preoperative risk factors for poor outcomes. Eight
      studies noted improvements in risk-adjusted mortality with registry
      participation; one found no change. A major limitation is bias from context and
      means of data collection threatening internal validity of registry quality
      measurement. Conversely, the other major limitation is the cost of participation,
      which threatens the external validity of registry quality measurement.
      CONCLUSION: Clinical registries have advanced surgical quality definition,
      measurement, and modeling as well as having served as platforms for local
      initiatives for quality improvement. The implication of this finding is that
      subsidizing registry participation may improve data validity as well as engage
      providers in quality improvement.

PMID- 25616952
TI  - Morbidity and mortality after total gastrectomy for gastric malignancy: do not
      forget about geriatric frailty and nutrition.

PMID- 25616953
TI  - Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism.
AB  - Neuroglobin (Ngb) is a recently discovered globin with preferential localization
      to neurons. Growing evidence indicates that Ngb has distinct physiological
      functions separate from the oxygen storage and transport roles of other globins,
      such as hemoglobin and myoglobin. We found increased ATP production and decreased
      glycolysis in Ngb-overexpressing immortalized murine hippocampal cell line (HT
      22), in parallel with inhibition of AMP-activated protein kinase (AMPK) signaling
      and activation of acetyl-CoA carboxylase (ACC). In addition, lipid and glycogen
      content was increased in Ngb-overexpressing HT-22 cells. AMPK signaling was also
      inhibited in the brain and heart from Ngb-overexpressing transgenic mice.
      Although Ngb overexpression did not change glycogen content in whole brain,
      glycogen synthase was activated in cortical neurons of Ngb-overexpressing mouse
      brain and Ngb overexpression primary neurons. Moreover, lipid and glycogen
      content was increased in hearts derived from Ngb-overexpressing mice. These
      findings suggest that Ngb functions as a metabolic regulator and enhances
      cellular anabolism through the inhibition of AMPK signaling. 

PMID- 25616955
TI  - Let's keep dancing.

PMID- 25616954
TI  - TLR9 gene region polymorphisms and susceptibility to tuberculosis in Vietnam.
AB  - Humans exposed to Mycobacterium tuberculosis (Mtb) show variation in
      susceptibility to infection and differences in tuberculosis (TB) disease outcome.
      Toll-like receptor 9 (TLR9) is a pattern recognition receptor that mediates
      recognition of Mtb and modulates Mtb-specific T-cell responses. Using a case
      population design, we evaluated whether single nucleotide polymorphisms (SNPs) in
      the TLR9 gene region are associated with susceptibility to pulmonary or meningeal
      TB as well as neurologic presentation and mortality in the meningeal TB group. In
      a discovery cohort (n = 352 cases, 382 controls), three SNPs were associated with
      TB (all forms, p < 0.05) while three additional SNPs neared significance (0.05 <
      p < 0.1). When these six SNPs were evaluated in a validation cohort (n = 339
      cases, 367 controls), one was significant (rs352142) while another neared
      significance (rs352143). When the cohorts were combined, rs352142 was most
      strongly associated with meningeal tuberculosis (dominant model; p = 0.0002, OR
      2.36, CI 1.43-3.87) while rs352143 was associated with pulmonary tuberculosis
      (recessive model; p = 0.006, OR 5.3, CI 1.26-31.13). None of the SNPs were
      associated with mortality. This is the first demonstration of an association
      between a TLR9 gene region SNP and tuberculous meningitis. In addition, this
      extends previous findings that support associations of TLR9 SNPs with pulmonary
      tuberculosis. 

PMID- 25616957
TI  - Training labels for hippocampal segmentation based on the EADC-ADNI harmonized
      hippocampal protocol.
AB  - BACKGROUND: The European Alzheimer's Disease Consortium and Alzheimer's Disease
      Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition
      of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can
      be used as the standard of truth to train new tracers, and to validate automated
      segmentation algorithms. Training requires large and representative data sets of
      segmented hippocampi. This work aims to produce a set of HarP labels for the
      proper training and certification of tracers and algorithms. METHODS: Sixty-eight
      1.5 T and 67 3 T volumetric structural ADNI scans from different subjects,
      balanced by age, medial temporal atrophy, and scanner manufacturer, were
      segmented by five qualified HarP tracers whose absolute interrater intraclass
      correlation coefficients were 0.953 and 0.975 (left and right). Labels were
      validated as HarP compliant through centralized quality check and correction.
      RESULTS: Hippocampal volumes (mm(3)) were as follows: controls: left = 3060
      (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment
      (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease
      (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly
      correlated with atrophy severity at Scheltens' scale (Spearman's rho = <-0.468, P
      = <.0005). Cerebrospinal fluid spaces (mm(3)) were as follows: controls: left =
      23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11
      (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy.
      CONCLUSIONS: This work provides reference hippocampal labels for the training and
      certification of automated segmentation algorithms. The publicly released labels
      will allow the widespread implementation of the standard segmentation protocol.

PMID- 25616958
TI  - Inference for Surrogate Endpoint Validation in the Binary Case.
AB  - Surrogate endpoint validation for a binary surrogate endpoint and a binary true
      endpoint is investigated using the criteria of proportion explained (PE) and the
      relative effect (RE). The concepts of generalized confidence intervals and
      fiducial intervals are used for computing confidence intervals for PE and RE. The
      numerical results indicate that the proposed confidence intervals are
      satisfactory in terms of coverage probability, whereas the intervals based on
      Fieller's theorem and the delta method fall short in this regard. Our methodology
      can also be applied to interval estimation problems in a causal inference-based
      approach to surrogate endpoint validation. 

PMID- 25616959
TI  - Nonsteroidal anti-inflammatory medications are cytostatic against human
      vestibular schwannomas.
AB  - Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine
      angle. Significant clinical need exists for pharmacotherapies against VSs.
      Motivated by previous findings that immunohistochemical expression of
      cyclooxygenase 2 (COX-2) correlates with VS growth rate, we investigated the role
      of COX-2 in VSs and tested COX-2 inhibiting salicylates against VSs. COX-2 was
      found to be aberrantly expressed in human VS and primary human VS cells in
      comparison with control human nerve specimens and primary Schwann cells (SCs),
      respectively. Furthermore, levels of prostaglandin E2, the downstream enzymatic
      product of COX-2, were correlated with primary VS culture proliferation rate.
      Because COX-2 inhibiting salicylates such as aspirin are well tolerated and
      frequently clinically used, we assessed their repurposing for VS. Changes in
      proliferation, cell death, and cell viability were analyzed in primary VS
      cultures treated with aspirin, sodium salicylate, or 5-aminosalicylic acid. These
      drugs neither increased VS cell death nor affected healthy SCs. The cytostatic
      effect of aspirin in vitro was in concurrence with our previous clinical finding
      that patients with VS taking aspirin demonstrate reduced tumor growth. Overall,
      this work suggests that COX-2 is a key modulator in VS cell proliferation and
      survival and highlights salicylates as promising pharmacotherapies against VS.

PMID- 25616961
TI  - ALS-linked mutations in ubiquilin-2 or hnRNPA1 reduce interaction between
      ubiquilin-2 and hnRNPA1.
AB  - Amyotrophic lateral sclerosis (ALS)-linked mutations in UBQLN2 and some members
      of the heterogeneous nuclear ribonucleoproteins (hnRNPs) family cause ALS. Most
      mutations in UBQLN2 are missense mutations that occur in and around a PXX repeat
      motif located in the central domain of the encoded protein. However, neither the
      function of the PXX motif nor the mechanism by which mutations in UBQLN2 cause
      ALS is known. We screened a yeast two-hybrid library using the central domain of
      ubiquilin-2 hoping to identify proteins whose binding is affected by the UBQLN2
      mutations. Three such interactors were identified-hnRNPA1, hnRNPA3 and hnRNPU-all
      members of the hnRNP family. The interacting region in each of these proteins was
      their glycine-rich domain, the domain most frequently mutated in hnRNP-related
      proteins that cause ALS. We focused on hnRNPA1, because a mutation in the protein
      causes ALS. We confirmed the interaction between wild-type (WT) ubiquilin-2 and
      hnRNPA1 proteins in vitro and in cells. In contrast, all five ALS mutations in
      ubiquilin-2 that we examined had reduced binding with WT hnRNPA1. In addition,
      hnRNPA1 carrying the D262V missense mutation that causes ALS failed to bind WT
      ubiquilin-2. Overexpression of ubiquilin-2 containing the ALS mutations increased
      cell death and, for several of the mutants, this correlated with increased
      translocation of hnRNPA1 to the cytoplasm. Knockdown of ubiquilin-2 led to
      increased turnover of hnRNPA1, indicating ubiquilin-2 functions to stabilize
      hnRNPA1. The discovery that ubiquilin-2 interacts with hnRNP proteins and that
      mutation in either protein disrupts interaction suggests a connection between
      proteostasis and RNA metabolism.

PMID- 25616960
TI  - Non-manifesting AHI1 truncations indicate localized loss-of-function tolerance in
      a severe Mendelian disease gene.
AB  - Determination of variant pathogenicity represents a major challenge in the era of
      high-throughput sequencing. Erroneous categorization may result if variants
      affect genes that are in fact dispensable. We demonstrate that this also applies
      to rare, apparently unambiguous truncating mutations of an established disease
      gene. By whole-exome sequencing (WES) in a consanguineous family with congenital
      non-syndromic deafness, we unexpectedly identified a homozygous nonsense variant,
      p.Arg1066*, in AHI1, a gene associated with Joubert syndrome (JBTS), a severe
      recessive ciliopathy. None of four homozygotes expressed any signs of JBTS, and
      one of them had normal hearing, which also ruled out p.Arg1066* as the cause of
      deafness. Homozygosity mapping and WES in the only other reported JBTS family
      with a homozygous C-terminal truncation (p.Trp1088Leufs*16) confirmed AHI1 as
      disease gene, but based on a more N-terminal missense mutation impairing WD40
      repeat formation. Morpholinos against N-terminal zebrafish Ahi1, orthologous to
      where human mutations cluster, produced a ciliopathy, but targeting near human
      p.Arg1066 and p.Trp1088 did not. Most AHI1 mutations in JBTS patients result in
      truncated protein lacking WD40-repeats and the SH3 domain; disease was hitherto
      attributed to loss of these protein interaction modules. Our findings indicate
      that normal development does not require the C-terminal SH3 domain. This has far
      reaching implications, considering that variants like p.Glu984* identified by
      preconception screening ('Kingsmore panel') do not necessarily indicate JBTS
      carriership. Genomes of individuals with consanguineous background are enriched
      for homozygous variants that may unmask dispensable regions of disease genes and
      unrecognized false positives in diagnostic large-scale sequencing and
      preconception carrier screening. 

PMID- 25616962
TI  - FGFR1 signaling in hypertrophic chondrocytes is attenuated by the Ras-GAP
      neurofibromin during endochondral bone formation.
AB  - Aberrant fibroblast growth factor receptor 3 (FGFR3) signaling disrupts
      chondrocyte proliferation and growth plate size and architecture, leading to
      various chondrodysplasias or bone overgrowth. These observations suggest that the
      duration, intensity and cellular context of FGFR signaling during growth plate
      chondrocyte maturation require tight, regulated control for proper bone
      elongation. However, the machinery fine-tuning FGFR signaling in chondrocytes is
      incompletely defined. We report here that neurofibromin, a Ras-GAP encoded by
      Nf1, has an overlapping expression pattern with FGFR1 and FGFR3 in
      prehypertrophic chondrocytes, and with FGFR1 in hypertrophic chondrocytes during
      endochondral ossification. Based on previous evidence that neurofibromin inhibits
      Ras-ERK signaling in chondrocytes and phenotypic analogies between mice with
      constitutive FGFR1 activation and Nf1 deficiency in Col2a1-positive chondrocytes,
      we asked whether neurofibromin is required to control FGFR1-Ras-ERK signaling in
      maturing chondrocytes in vivo. Genetic Nf1 ablation in Fgfr1-deficient
      chondrocytes reactivated Ras-ERK1/2 signaling in hypertrophic chondrocytes and
      reversed the expansion of the hypertrophic zone observed in mice lacking Fgfr1 in
      Col2a1-positive chondrocytes. Histomorphometric and gene expression analyses
      suggested that neurofibromin, by inhibiting Rankl expression, attenuates pro
      osteoclastogenic FGFR1 signaling in hypertrophic chondrocytes. We also provide
      evidence suggesting that neurofibromin in prehypertrophic chondrocytes,
      downstream of FGFRs and via an indirect mechanism, is required for normal
      extension and organization of proliferative columns. Collectively, this study
      indicates that FGFR signaling provides an important input into the Ras-Raf-MEK
      ERK1/2 signaling axis in chondrocytes, and that this input is differentially
      regulated during chondrocyte maturation by a complex intracellular machinery, of
      which neurofibromin is a critical component. 

PMID- 25616963
TI  - A systematic investigation of the contribution of genetic variation within the
      MHC region to HPV seropositivity.
AB  - High-risk mucosal types of human papillomavirus (HPV) cause anogenital and
      oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected
      to be involved in non-melanoma skin cancer. The antibody response to HPVs is a
      key determinant of protective immunity, but not all infected individuals
      seroconvert. Genetic variability of the host may have large impact on
      seroconversion. A previous genome-wide association study (GWAS) has identified a
      susceptibility locus (rs41270488) for HPV8 seropositivity within the major
      histocompatibility complex (MHC) region. To further study this locus, we imputed
      alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a
      reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted
      an integrated analysis among 4811 central European subjects to assess the
      contribution of classical HLA alleles and gene copy number variation (CNV) at the
      hypervariable DRB locus within the MHC region to HPV seropositivity at both the
      individual HPV type level and the phylogenetic species level. Our study provides
      evidence that the association noted between rs41270488 and HPV8 seropositivity is
      driven by two independent variants, namely DQB1*0301 [odds ratio (OR) = 1.51, 95%
      confidence interval (CI) = 1.36-1.68, P = 1.0 * 10(-14)] and DRB1*1101 (OR =
      1.89, 95%CI = 1.57-2.28, P = 1.5 * 10(-11)) within the HLA class II region.
      Additionally, we identified two correlated alleles DRB1*0701 (OR = 1.67, 95%CI =
      1.41-1.98, P = 2.6 * 10(-9)) and DQA1*0201 (OR = 1.67, 95%CI = 1.38-1.93, P = 1.7
      * 10(-8)), to be associated with HPV77 seropositivity. Comparable results were
      observed through imputation using SNP2HLA with another reference panel from the
      Type 1 diabetes Genetics Consortium. This study provides support for an important
      role of HLA class II alleles in antibody response to HPV infection.

PMID- 25616964
TI  - Animals deficient in C2Orf71, an autosomal recessive retinitis pigmentosa
      associated locus, develop severe early-onset retinal degeneration.
AB  - Genetic mapping was recently used to identify the underlying cause for a
      previously uncharacterized cohort of autosomal recessive retinitis pigmentosa
      cases. Genetic mapping of affected individuals resulted in the identification of
      an uncharacterized gene, C2Orf71, as the causative locus. However, initial
      homology searches failed to reveal similarities to any previously characterized
      protein or domain. To address this issue, we characterized the mouse homolog,
      BC027072. Immunohistochemistry with a custom polyclonal antibody showed staining
      localized to the inner segments (IS) of photoreceptor cells, as well as the outer
      segments (OS) of cone cells. A knockout mouse line (BC(-/-)) was generated and
      demonstrated that loss of this gene results in a severe, early-onset retinal
      degeneration. Histology and electron microscopy (EM) revealed disorganized OS as
      early as 3 weeks with complete loss by 24 weeks of age. EM micrographs displayed
      packets of cellular material containing OS discs or IS organelles in the OS
      region and abnormal retinal pigmented epithelium cells. Analyses of retinoids and
      rhodopsin levels showed <20% in BC(-/-) versus wild-type mice early in
      development. Electroretinograms demonstrated that affected mice were virtually
      non-responsive to light by 8 weeks of age. Lastly, RNAseq analysis of ocular gene
      expression in BC(-/-) mice revealed clues to the causes of the progressive
      retinal degenerations. Although its function remains unknown, this protein
      appears essential for normal OS development/maintenance and vision in humans and
      mice. RNAseq data are available in the GEO database under accession: GSE63810.

PMID- 25616965
TI  - A Huntingtin-based peptide inhibitor of caspase-6 provides protection from mutant
      Huntingtin-induced motor and behavioral deficits.
AB  - Over the past decade, increasing evidence has implied a significant connection
      between caspase-6 activity and the pathogenesis of Huntington's disease (HD).
      Consequently, inhibiting caspase-6 activity was suggested as a promising
      therapeutic strategy to reduce mutant Huntingtin toxicity, and to provide
      protection from mutant Huntingtin-induced motor and behavioral deficits. Here, we
      describe a novel caspase-6 inhibitor peptide based on the huntingtin caspase-6
      cleavage site, fused with a cell-penetrating sequence. The peptide reduces mutant
      Huntingtin proteolysis by caspase-6, and protects cells from mutant Huntingtin
      toxicity. Continuous subcutaneous administration of the peptide protected pre
      symptomatic BACHD mice from motor deficits and behavioral abnormalities.
      Moreover, administration of the peptide in an advanced disease state resulted in
      the partial recovery of motor performance, and an alleviation of depression
      related behavior and cognitive deficits. Our findings reveal the potential of
      substrate-based caspase inhibition as a therapeutic strategy, and present a
      promising agent for the treatment of HD. 

PMID- 25616966
TI  - miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells
      through activating the transcription of heparanase.
AB  - Heparanase (HPSE) is the endogenous endoglycosidase that degrades heparan sulfate
      proteoglycans and promotes the tumor growth, invasion, metastasis and
      angiogenesis. Our previous studies have shown that HPSE is highly expressed in
      neuroblastoma (NB), the most common extracranial solid tumor in childhood.
      However, the underlying regulatory mechanisms remain largely unknown. In this
      study, we identified one binding site of microRNA-558 (miR-558) within the HPSE
      promoter. In NB tissues and cell lines, miR-558 was up-regulated and positively
      correlated with HPSE expression. Gain- and loss-of-function studies demonstrated
      that miR-558 facilitated the transcript and protein levels of HPSE and its
      downstream gene, vascular endothelial growth factor, in NB cell lines. In
      addition, miR-558 enhanced the promoter activities of HPSE, and these effects
      were abolished by the mutation of the miR-558-binding site. Mechanistically, miR
      558 induced the enrichment of the active epigenetic marker and RNA polymerase II
      on the HPSE promoter in NB cells in an Argonaute 1-dependent manner, which was
      abolished by repressing the miR-558-promoter interaction. Knockdown of endogenous
      miR-558 decreased the growth, invasion, metastasis and angiogenesis of NB cells
      in vitro and in vivo. In contrast, over-expression of miR-558 promoted the
      growth, invasion, metastasis and angiogenesis of SH-SY5Y and SK-N-SH cells.
      Restoration of HPSE expression prevented the NB cells from changes in these
      biological features induced by knockdown or over-expression of miR-558. These
      data indicate that miR-558 induces the transcriptional activation of HPSE via the
      binding site within promoter, thus facilitating the tumorigenesis and
      aggressiveness of NB. 

PMID- 25616967
TI  - Comparative pharmacokinetic properties and antitumor activity of the marine HDACi
      Largazole and Largazole peptide isostere.
AB  - PURPOSE: Largazole is a potent class I-selective HDACi natural product isolated
      from the marine cyanobacteria Symploca sp. The purpose of this study was to test
      synthetic analogs of Largazole to identify potential scaffold structural
      modifications that would improve the drug-like properties of this clinically
      relevant natural product. METHODS: The impact of Largazole scaffold replacements
      on in vitro growth inhibition, cell cycle arrest, induction of apoptosis,
      pharmacokinetic properties, and in vivo activity using a xenograft model was
      investigated. RESULTS: In vitro studies in colon, lung, and pancreatic cancer
      cell lines showed that pyridyl-substituted Largazole analogs had low
      nanomolar/high-picomolar antiproliferative activity, and induced apoptosis and
      cell cycle arrest at concentrations equivalent to or lower than the parent
      compound Largazole. Using IV bolus delivery at 5 mg/kg, two compartmental
      pharmacokinetic modeling on the peptide isostere analog of Largazole indicated
      improved pharmacokinetic parameters. In an A549 non-small cell lung carcinoma
      xenograft model using a dosage of 5 mg/kg administered intraperitoneally every
      other day, Largazole, Largazole thiol, and Largazole peptide isostere
      demonstrated tumor growth inhibition (TGI%) of 32, 44, and 66%, respectively.
      Largazole peptide isostere treatment was statistically superior to control (p =
      0.002) and to Largazole (p = 0.006). Surprisingly, tumor growth inhibition was
      not observed with the potent pyridyl-based analogs. CONCLUSIONS: These results
      establish that replacing the depsipeptide linkage in Largazole with an amide may
      impart pharmacokinetic and therapeutic advantage and that alternative prodrug
      forms of Largazole are feasible.

PMID- 25616968
TI  - Vortex-assisted magnetic beta-cyclodextrin/attapulgite-linked ionic liquid
      dispersive liquid-liquid microextraction coupled with high-performance liquid
      chromatography for the fast determination of four fungicides in water samples.
AB  - A novel microextraction technique combining magnetic solid-phase microextraction
      (MSPME) with ionic liquid dispersive liquid-liquid microextraction (IL-DLLME) to
      determine four fungicides is presented in this work for the first time. The main
      factors affecting the extraction efficiency were optimized by the one-factor-at-a
      time approach and the impacts of these factors were studied by an orthogonal
      design. Without tedious clean-up procedure, analytes were extracted from the
      sample to the adsorbent and organic solvent and then desorbed in acetonitrile
      prior to chromatographic analysis. Under the optimum conditions, good linearity
      and high enrichment factors were obtained for all analytes, with correlation
      coefficients ranging from 0.9998 to 1.0000 and enrichment factors ranging 135 and
      159 folds. The recoveries for proposed approach were between 98% and 115%, the
      limits of detection were between 0.02 and 0.04 MUg L(-1) and the RSDs changed
      from 2.96 to 4.16. The method was successfully applied in the analysis of four
      fungicides (azoxystrobin, chlorothalonil, cyprodinil and trifloxystrobin) in
      environmental water samples. The recoveries for the real water samples ranged
      between 81% and 109%. The procedure proved to be a time-saving, environmentally
      friendly, and efficient analytical technique.

PMID- 25616969
TI  - An analysis method for simultaneous screening of deoxyribonucleic acid-binding
      active compounds and investigating their mechanisms by ultra-fast liquid
      chromatography tandem mass spectrometry coupled with fluorescence detection
      technology.
AB  - DNA has been known as the cellular target for many cytotoxic anticancer agents
      over the years. Discovering DNA-binding compounds has become an active research
      area, while various DNA-binding mechanisms make the drug discovery even more
      difficult. In this article, we present a novel analysis method to rapidly
      identify specific DNA-binding compounds from Pyrrosia lingua (Thunb.) using DNA
      dual-fluorescent probes, ethidium bromide and Hoechst 33258, with the technology
      of ultra-fast liquid chromatography-diode array detector-tandem mass spectrometry
      and dual-wavelength fluorescence detector (UFLC-DAD-MS(n)-DFLD). Sixty-two
      compounds were identified, of which 22 were found to be active in DNA-binding.
      After investigation of their dose-response behaviors and structure-activity
      relationships, chlorogenic acids and flavonoid glycosides were found to be DNA
      binders via both minor groove-binding and intercalation modes. The precision,
      reproducibility and stability of this method were validated by vitexin. The
      established system was sensitive, precise, and reliable to be used for both
      screening of DNA-binding compounds and investigating of their mechanisms. 

PMID- 25616970
TI  - Functionalized gold nanoparticle-polypyrrole nanobiocomposite with high effective
      surface area for electrochemical/pH dual stimuli-responsive smart release of
      insulin.
AB  - A novel functionalized gold nanoparticle-polypyrrole-nanobiocomposite (PPy-FGNP
      NBC) with large effective surface area was fabricated for electrical/pH dual
      stimuli-responsive local delivery of insulin. The fabrication method involves
      simple electrodeposition and immobilization processes without use of organic
      solvents. Release studies based on the nature of insulin-surface binding
      indicated that release was promoted for PPy-FGNP-NBC. Kinetics analysis showed
      that release of insulin strongly affected by applying external potential stimuli.
      Also, the insulin release was under influence of pH and was slowed down under
      lower pH. This pH-sensitivity was remarkably increased by applying potential.
      Based on in vitro release study under applied potential condition, insulin
      release in the artificial gastric juice is significantly slower than that in the
      artificial intestinal fluid. Circular dichroism analysis showed that insulin
      retained its original conformation during electrochemically stimulated release. 

PMID- 25616971
TI  - Arteether nanoemulsion for enhanced efficacy against Plasmodium yoelii
      nigeriensis malaria: an approach by enhanced bioavailability.
AB  - The present work is focused on the preparation of nanoemulsions (NEs) loaded with
      arteether (ART) for its enhanced efficacy against malaria parasites. ART-NEs have
      been prepared using high pressure homogenization (HPH) technique with the aim of
      improving its solubility and thus its bioavailability. ART-NEs were optimized in
      terms of pressure and number of cycles. Globule size and size distributions were
      chosen as quality parameters. The maximum drug loading was achieved up to 93 +/-
      7.4% with globule size 156 +/- 10.2 nm and zeta potential of -23.3 +/- 3.4 mV.
      The developed ART-NEs were found to be stable in terms of globule size and size
      distribution at different pH. The in vitro release profile of the ART-NEs showed
      62% drug release within 12h. The percentage cell viability of blank NEs were
      within acceptable limits. A sensitive assay method for the determination of ART
      in rat plasma by liquid chromatography-mass spectrometry (LC-MS) was employed
      after oral administration of ART-NEs. The pharmacokinetic study showed
      significantly enhanced bioavailability of ART in ART-NE-V. The area under curve
      (AUC) of ART-NE-V was AUC0-t 1988.411 +/- 119.66 h ng/ml which was significantly
      higher (p<0.05) than ART in ground nut oil (GNO) AUC0-t 671.852 +/- 187.05 h
      ng/ml. The Cmax of ART-NE-V (1506 +/- 161.22 ng/ml) was also significantly higher
      (p<0.05) than ART in GNO (175.2 +/- 16.54 ng/ml) and ART given intramuscularly
      (IM) (278.05 +/- 38.59 ng/ml). The ART-NE-V was having significantly high
      antimalarial efficacy and survival rate of mice giving 80% cure rate at 12.5
      mg/kg for 5 days in comparison to 30% cure rate of ART in GNO at the same daily
      dose and it was also comparable to the 100% cure rate at 12.5 mg/kg for 5 days
      for ART given intramuscularly. In conclusion ART-NE can be a promising oral
      delivery system for ART.

PMID- 25616972
TI  - Carboxylic group-induced synthesis and characterization of selenium nanoparticles
      and its anti-tumor potential on Dalton's lymphoma cells.
AB  - Carboxylic group-induced synthesis of selenium nanoparticles (SeNPs) was achieved
      using sodium selenosulphate as a precursor. The particles were stabilized and
      capped with 0.01% polyvinyl alcohol under ambient conditions. This is a simple
      and easy method of producing SeNPs in a size range from 35 to 105 nm. The
      synthesized SeNPs were purified by centrifugation at 11,500 * g for 20 min and
      characterized by UV-visible spectroscopy, FTIR spectroscopy, XRD, DSC and TEM. It
      was observed that the synthesized SeNPs showed differences in their absorption
      spectra, phase composition and crystal structure, thermodynamic behaviour, size
      and shape. Further, to confirm anti-tumour potential of the synthesized SeNPs
      induced by the carboxylic group of acetic acid, pyruvic acid and benzoic acid,
      cell viability assay, nuclear morphology testing and DNA fragmentation assay were
      carried out using Dalton's lymphoma (DL) cells. DL cells treated with the SeNPs
      showed reduced cell viability, altered nuclear morphology, typical apoptotic DNA
      ladder and apoptosis. Therefore, these SeNPs may have therapeutic relevance to
      treat this type of cancer.

PMID- 25616973
TI  - Anticipating rotavirus vaccines--a pre-vaccine assessment of incidence and
      economic burden of rotavirus hospitalizations among children < 5 year of age in
      Libya, 2012-13.
AB  - BACKGROUND: Libya introduced rotavirus vaccine in October 2013. We examined pre
      vaccine incidence of rotavirus hospitalizations and associated economic burden
      among children < 5 years in Libya to provide baseline data for future vaccine
      impact evaluations. METHODS: Prospective, hospital-based active surveillance for
      rotavirus was conducted at three public hospitals in two cities during August
      2012 - April 2013. Clinical, demographic and estimated cost data were collected
      from children <5 hospitalized for diarrhea; stool specimens were tested for
      rotavirus with a commercial enzyme immunoassay. Annual rotavirus hospitalization
      incidence rate estimates included a conservative estimate based on the number of
      cases recorded during the nine months and an extrapolation to estimate 12 months
      incidence rate. National rotavirus disease and economic burden were estimated by
      extrapolating incidence and cost data to the national population of children aged
      < 5 years. RESULTS: A total of 410 children < 5 years of age with diarrhea were
      enrolled, of whom 239 (58%) tested positive rotavirus, yielding an incidence
      range of 418-557 rotavirus hospitalizations per 100,000 children < 5 years of
      age. Most (86%) rotavirus cases were below two years of age with a distinct
      seasonal peak in winter (December-March) months. The total cost of treatment for
      each rotavirus patient was estimated at US$ 679 (range: 200-5,423). By
      extrapolation, we estimated 2,948 rotavirus hospitalizations occur each year in
      Libyan children < 5 years of age, incurring total costs of US$ 2,001,662 (range:
      1,931,726-2,094,005). CONCLUSIONS: Rotavirus incurs substantial morbidity and
      economic burden in Libya, highlighting the potential value of vaccination of
      Libyan children against rotavirus.

PMID- 25616974
TI  - Lower maximum standardized uptake value of fluorine-18 fluorodeoxyglucose
      positron emission tomography coupled with computed tomography imaging in
      pancreatic ductal adenocarcinoma patients with diabetes.
AB  - BACKGROUND: The effects of diabetes mellitus (DM) on sensitivity of fluorine-18
      fluorodeoxyglucose positron emission tomography coupled with computed tomography
      ((18)F-FDG PET/CT) for diagnosing pancreatic ductal adenocarcinomas (PDACs) is
      not well known. This study was aimed to evaluate the effects of DM on the
      validity of (18)F-FDG PET/CT in PDAC. METHODS: A total of 173 patients with PDACs
      who underwent (18)F-FDG PET/CT were enrolled (75 in the DM group and 98 in the
      non-DM group). The maximum standardized uptake values (SUVsmax) were compared.
      RESULTS: The mean SUVmax was significantly lower in the DM group than in the non
      DM group (4.403 vs 5.998, P = .001). The sensitivity of SUVmax (cut-off value
      4.0) was significantly lower in the DM group than in the non-DM group (49.3% vs
      75.5%, P < .001) and also lower in normoglycemic DM patients (n = 24) than in non
      DM patients (54.2% vs 75.5%, P = .038). CONCLUSION: DM contributes to a lower
      SUVmax of (18)F-FDG PET/CT in patients with PDACs.

PMID- 25616975
TI  - Predictive utility of the changes in matrix metalloproteinase-2 in the early
      phase for left ventricular reverse remodeling after an acute myocardial
      infarction.
AB  - BACKGROUND: The relationship between the serum levels of matrix metalloproteinase
      (MMP) and tissue inhibitors of MMP (TIMP) and left ventricular (LV) reverse
      remodeling (LV-RR) after an acute myocardial infarction (AMI) has not been
      sufficiently examined. METHODS AND RESULTS: In 25 patients with successful
      reperfusion after an AMI and 15 normal control subjects, the serum MMP-2 and TIMP
      2 levels were measured on days 1, 2, 3, and 7 and at 1 and 6 months after the AMI
      onset. LV-RR was defined as a >15% decrease in the LV end-systolic volume index
      at 6 months after the AMI. The MMP-2 level on day 1 and TIMP-2 levels throughout
      the study period were comparable between the patients with and without LV-RR. The
      MMP-2 on day 7 (P<0.05) and the changes in the MMP-2 from day 1 to day 7 (?MMP-2;
      P<0.01) were lower in patients with than in those without LV-RR. The ?MMP-2 was
      strongly correlated with the changes in the LV volume and ejection fraction from
      1 month to 6 months after the AMI. The ?MMP-2 value of <-158.5 ng/mL predicted LV
      RR with a high accuracy (91.7% sensitivity and 76.9% specificity; area under the
      curve=0.82). CONCLUSIONS: Changes in MMP-2 are associated with LV-RR after an
      AMI. The DeltaMMP-2 might be a useful predictor of subsequent LV-RR.

PMID- 25616976
TI  - Arrhythmogenic cardiomyopathy in a patient with a rare loss-of-function KCNQ1
      mutation.
AB  - BACKGROUND: Ventricular tachycardia (VT) is a common manifestation of advanced
      cardiomyopathies. In a subset of patients with dilated cardiomyopathy, VT is the
      initial and the cardinal manifestation of the disease. The molecular genetic
      basis of this subset of dilated cardiomyopathy is largely unknown. METHODS AND
      RESULTS: We identified 10 patients with dilated cardiomyopathy who presented with
      VT and sequenced 14 common causal genes for cardiomyopathies and arrhythmias.
      Functional studies included cellular patch clamp, confocal microscopy, and
      immunoblotting. We identified nonsynonymous variants in 4 patients, including a
      rare missense p.R397Q mutation in the KCNQ1 gene in a 60-year-old man who
      presented with incessant VT and had mild cardiac dysfunction. The p.R397Q
      mutation was absent in an ethnically matched control group, affected a conserved
      amino acid, and was predicted by multiple algorithms to be pathogenic. Co
      expression of the mutant KCNQ1 with its partner unit KCNE1 was associated with
      reduced tail current density of slowly activating delayed rectifier K(+) current
      (IKs). The mutation reduced membrane localization of the protein. CONCLUSIONS:
      Dilated cardiomyopathy with an initial presentation of VT may be a forme fruste
      of arrhythmogenic cardiomyopathy caused by mutations in genes encoding the ion
      channels. The findings implicate KCNQ1 as a possible causal gene for
      arrhythmogenic cardiomyopathy.

PMID- 25616977
TI  - Bioengineered tumors.
AB  - Three-dimensional (3D) tumor models generated in vitro using methods of tissue
      engineering are just starting to show potential for predictive studies of
      therapeutic targets and screening of anticancer drugs. By mimicking some of the
      key features of the in vivo tumor environment, these models allow us to grow
      physiologically relevant tumors and study the initiation, progression and
      metastasis. Using a recent report on how to engineer bone tumors, we comment on
      the state-of-the-art in bioengineered bone tumors, with focus on the components
      required for recapitulating the in vivo milieu of bone tumor development. 

PMID- 25616978
TI  - The influence of normative and subjective oral health status on schoolchildren's
      happiness.
AB  - BACKGROUND: Traditional methods to measure oral health based on clinical
      standards are limited because they do not consider psychosocial and functional
      aspects of oral health. It has been recommended that these measures need to be
      supplemented by data obtained from patients regarding their individual
      perceptions on oral health-related quality of life (OHRQoL). Happiness is a
      multidimensional construct comprising both emotional and cognitive domains, and
      has been defined as "the degree to which an individual judges the overall quality
      of his or her life as a whole favorably". It has been associated with several
      health outcomes, including oral health. The aim of this study was to assess the
      impact of oral health conditions, oral health-related quality of life (OHRQoL),
      and socioeconomic factors on the subjective happiness of Brazilian adolescents.
      METHODS: A cross-sectional study was conducted in 2012 on a representative sample
      of 12-year-old schoolchildren in Santa Maria-RS, Brazil. The data were collected
      through dental examinations and structured interviews. The participants underwent
      an evaluation aimed at detecting dental caries, traumatic dental injuries,
      malocclusion, and gingival bleeding. They also completed the Brazilian versions
      of the Child Perceptions Questionnaire-short form (CPQ11-14-ISF: 16) and the
      Subjective Happiness Scale (SHS), which was our outcome variable. Socioeconomic
      conditions were evaluated through a questionnaire that was completed by the
      participants' parents. Poisson regression analysis was used to determine the
      association between the explanatory variables and the outcome. Moreover, a
      correlation analysis was performed to determine the relationship between the SHS
      scores and the overall and domain scores of the CPQ11-14-ISF: 16. RESULTS: A
      total of 1,134 children were evaluated. Unadjusted analyses showed that happiness
      was associated with socioeconomic indicators, the use of dental services,
      clinical status, and scores on the OHRQoL measure. After adjustment, household
      overcrowding (RR: 0.96; 95% CI: 0.93-0.98), dental caries (RR: 0.98; 95% CI: 0.97
      0.99), malocclusion (RR: 0.98; 95% CI: 0.96-0.99), and the severity associated
      with the CPQ11-14 (RR: 0.95; 95% CI: 0.93-0.97) still showed a significant
      association with lower levels of the mean SHS score. CONCLUSIONS: Happiness is
      influenced by oral conditions, socioeconomic status, and OHRQoL.

PMID- 25616980
TI  - Letter to the editor.

PMID- 25616979
TI  - The association of the treatment with glucagon-like peptide-1 receptor agonist
      exenatide or insulin with cardiovascular outcomes in patients with type 2
      diabetes: a retrospective observational study.
AB  - BACKGROUND: To evaluate the association of treatment with glucagon-like peptide-1
      (GLP-1) receptor agonist exenatide and/or insulin on macrovascular outcomes in
      patients with type 2 diabetes (T2DM). METHODS: We conducted a retrospective
      longitudinal pharmaco-epidemiological study using large ambulatory care data to
      evaluate the risks of heart failure (HF), myocardial infarction (MI) and stroke
      in established T2DM patients who received a first prescription of exenatide twice
      daily (EBID) or insulin between June 2005 and May 2009, with follow-up data
      available until December 2012. Three treatment groups were: EBID with oral
      antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n =
      28551), and those who changed medications between EBID and insulin or had
      combination of EBID and insulin during follow-up, along with OADs (EBID +
      insulin, n = 7870). Multivariate Cox-regression models were used to evaluate the
      association of treatment groups with the risks of macrovascular events. RESULTS:
      During a median 3.5 years of follow-up, cardiovascular event rates per 1000
      person-years were significantly lower for the EBID and EBID + insulin groups
      compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5;
      stroke: 2.4 and 1.8 vs. 6.1). Patients in the EBID/EBID + insulin group had
      significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63%
      respectively, compared to patients in the insulin group (p < 0.01). CONCLUSIONS:
      Treatment with exenatide, with or without concomitant insulin was associated with
      reduced macrovascular risks compared to insulin; although inherent potential bias
      in epidemiological studies should be considered.

PMID- 25616981
TI  - Seroprevalence of foot-and-mouth disease in the southern provinces of Cambodia.
AB  - A serological surveillance study was conducted between March and June 2006 in the
      southern provinces of Cambodia to determine the prevalence and distribution of
      foot-and-mouth disease. Cattle and buffalo originating from eight provinces and
      69 villages were sampled. The results revealed that the village level prevalence
      of foot-and-mouth disease (FMD) in the southern provinces of Cambodia was 87%
      with an overall individual animal prevalence of 30%. Three serotypes: O, A and
      Asia 1 were detected in this region with a prevalence of 28.5, 9.5 and 9.3%,
      respectively. However, as the antibody level to FMDV serotypes A and Asia 1 were
      generally low, it is likely that serotype O is responsible for most of the recent
      outbreaks of FMD in Cambodia. Seropositive animals were older than seronegative
      animals, especially with serotype O.

PMID- 25616982
TI  - Evaluating pasture and soil allowance of manganese for Kajli rams grazing in semi
      arid environment.
AB  - The current research on the manganese (Mn) transfer from soil to plant as well as
      to grazing Kajli rams in the form of sampling periods was carried out under semi
      arid environmental conditions. Forage, soil and blood plasma samples were
      collected during 4 months of the year after a 1-month interval, and Mn
      concentrations were assessed after wet digestion using an atomic absorption
      spectrophotometer. Results showed that Mn concentration in soil ranged from 48.28
      to 59.44 mg/kg, with incoherent augment and decline across sampling periods, and
      effect of sampling period on soil Mn was also found to be significant (P < 0.05).
      The mean levels of Mn in soil appeared higher than the critical value and
      sufficient for forage crop requirement. The Mn concentration in forage ranged
      between 24.8 and 37.2 mg/kg, resulting deficient based on the requirement
      allowance of Mn for livestock grazing animals, therein with almost unchanged
      forage Mn concentration. The Mn values in blood plasma of rams varied from 0.066
      to 0.089 mg/l, with a consistent increase based on sampling period, and the
      effect of sampling periods on plasma Mn was found to be highly significant (P <
      0.05). The Mn levels in ram blood plasma were lesser than the normal level
      suggesting reasonable need for supplementation. Our study revealed the role of Mn
      availability in soil and plant species amassing capability on the transport of Mn
      in the soil-plant-animal system. Results indicated a much higher accumulation
      rate at the sampling characterized by vegetation dominated by legumes in
      comparison to grasses, crop residues and mixed pasture and a pronounced seasonal
      supply of Mn at the four sampling period of grazing land of diverse botanical
      composition. 

PMID- 25616983
TI  - Seasonal variation of fibre follicle activity and wool growth in fat-tailed
      Sanjabi sheep in west Iran.
AB  - This experiment was conducted to investigate the seasonal pattern of hair
      follicle activity, wool growth and fibre diameter (FD) in Sanjabi sheep in west
      Iran, Kermanshah (34 degrees  18' N and 47 degrees  3' E, elevation 1420 m). Ten
      male and 10 female Sanjabi sheep with an initial live weight of 32.1 +/- 1.3 and
      32.7 +/- 1.5 (means +/- SD), respectively, were used in a 365-day study. A diet
      was offered with an estimated concentration of 2.18 Mcal metabolizable energy and
      130.0 g/kg DM crude protein. Body weight, average daily gain (ADG) and dry matter
      intake (DMI) were recorded weekly. The percentages of active primary and
      secondary wool follicles (PAP and PAS), follicle density and the ratio of
      secondary to primary follicles (S/P) were determined from skin biopsies, taken
      from the right mid-side of the sheep at monthly intervals. Raw and clean fibre
      growth rates and FD were measured from left mid-side patches (10 * 10 cm)
      harvested at the end of every month. There was a gradual increase in live weight
      throughout the experiment, while ADG and DMI changed in concert with day length.
      The greatest values for PAP and PAS were observed in summer, whereas lowest were
      obtained in winter (p < 0.001). Clean wool growth rate and FD were greatest (p <
      0.001) in summer and lowest (p < 0.001) in winter. It is concluded that a
      seasonal cycle of feed intake, body growth, fibre follicle activity, wool growth
      and FD occur in fat-tailed Sanjabi sheep.

PMID- 25616984
TI  - Epidemiology of bovine viral diarrhoea among tropical small holder dairy units in
      Kerala, India.
AB  - Prevalence of bovine viral diarrhoea among 385 dairy cattle reared under a small
      holder system in Trichur District of Kerala State in India was determined through
      an ELISA targeting antibodies against p80-p125 non-structural protein of the
      virus. Prevalence was 24.7% among the total population, but was higher (52%) when
      85 animals having infertility problems alone were considered. Significant serum
      biochemistry differences between animals could be noticed only in total protein,
      globulin and phosphorous, all of which were low in seropositive animals. All
      animals which were seronegative for antibodies were screened by another ELISA
      targeting the E(rns) protein of the viral nucleocapsid to detect persistently
      infected (PI) animals. The single, positive animal had only a transient period of
      antigens in the blood, indicating absence of PI animals in the study population.
      High prevalence of the disease in isolated small holder units even in the absence
      of PI animals is discussed in view of identifying the common source of infection
      and initiating control measures.

PMID- 25616985
TI  - Development of loop-mediated isothermal amplification test for the diagnosis of
      contagious agalactia in goats.
AB  - Contagious agalactia is a highly infectious disease affecting sheep and goats,
      mainly caused by Mycoplasma agalactiae. Although various tests are available for
      diagnosis of contagious agalactia, none of them is credited with the capacity to
      provide rapid and cost-effective diagnosis. This article reports the development
      of loop-mediated isothermal amplification (LAMP) test targeting the p40 gene of
      M. agalactiae, for the diagnosis of classical contagious agalactia. Optimum
      amplification was obtained at 58  degrees C in 70 min. The developed test was
      found to be 100-fold more sensitive than PCR and detected up to 20-fg level of
      DNA. The test was also superior to conventional PCR in detecting from
      artificially contaminated milk, i.e. 10(4)-fold more sensitive. The developed
      LAMP test could detect up to 10 cfu/ml of artificially contaminated milk,
      indicating its potential for being developed as a field test for rapid and
      sensitive diagnosis.

PMID- 25616986
TI  - Risk factors associated with occurrence of African swine fever outbreaks in
      smallholder pig farms in four districts along the Uganda-Kenya border.
AB  - A cross-sectional survey was carried out to assess risk factors associated with
      occurrence of African swine fever (ASF) outbreaks in smallholder pig farms in
      four districts along Kenya-Uganda border. Information was collected by
      administering questionnaires to 642 randomly selected pig households in the study
      area. The study showed that the major risk factors that influenced ASF occurrence
      were purchase of pigs in the previous year (p < 0.000) and feeding of pigs with
      swill (p < 0.024). By employing cluster analysis, three clusters of pig
      production types were identified based on production characteristics that were
      found to differ significantly between districts. The most vulnerable cluster to
      ASF was households with the highest reported number of ASF outbreaks and composed
      of those that practiced free range at least some of the time. The majority of the
      households in this cluster were from Busia district in Uganda. On the other hand,
      the least vulnerable cluster to ASF composed of households that had the least
      number of pig purchases, minimal swill feeding, and less treatment for internal
      and external parasites. The largest proportion of households in this cluster was
      from Busia district Kenya. The study recommended the need to sensitize farmers to
      adopt proper biosecurity practices such as total confinement of pigs, treatment
      of swill, isolation of newly purchased pigs for at least 2 weeks, and provision
      of incentives for farmers to report suspected outbreaks to authorities and rapid
      confirmation of outbreaks.

PMID- 25616987
TI  - Simultaneous Determination of Tramadol and Its Metabolite in Human Urine by the
      Gas Chromatography-Mass Spectrometry Method.
AB  - A sensitive and efficient method was developed for determination of tramadol and
      its metabolite (O-desmethyltramadol) in human urine by gas chromatography-mass
      spectrometry. Tramadol, O-desmethyltramadol and medazepam (internal standard)
      were extracted from human urine with a mixture of ethylacetate and diethylether
      mixture (1 : 1, v/v) at basic pH with liquid-liquid extraction. The calibration
      curves were linear (r = 0.99) over tramadol and O-desmethyltramadol
      concentrations ranging from 10 to 200 ng/mL and 7.5 to 300 ng/mL, respectively.
      The method had an accuracy of >95% and intra- and interday precision (relative
      standard deviation %) of <=4.93 and <=4.62% for tramadol and O-desmethyltramadol,
      respectively. The extraction recoveries were found to be 94.1 +/- 2.91 and 96.3
      +/- 3.46% for tramadol and O-desmethyltramadol, respectively. The limit of
      quantification using 0.5 mL human urine was 10 ng/mL for tramadol and 7.5 ng/mL
      for O-desmethyltramadol. After oral administration of 100 mg of tramadol
      hydrochloride to a patient, the urinary excretion was monitored during 24 h.
      About 15% of the dose was excreted as unchanged tramadol. 

PMID- 25616988
TI  - Validated LC-MS/MS Assay for the Quantitative Determination of Fimasartan in
      Human Plasma: Application to Pharmacokinetic Studies.
AB  - A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method for the quantification of a newly developed antihypertensive agent
      fimasartan (BR-A657, Kanarb((r))) in human plasma was developed and validated.
      Fimasartan and internal standard (IS, BR-A563) were extracted by simple protein
      precipitation using acetonitrile and separated on a Phenyl-Hexyl column
      (Luna((r)), 5 um, 50 mm * 2.0 mm, Phenomenex) under the gradient conditions of
      mobile phase A (distilled water with 0.1% formic acid) and mobile phase B (100%
      acetonitrile with 0.1% formic acid) at a flow rate of 0.25 mL/min. Detection and
      quantification were performed by the mass spectrometer using multiple reaction
      monitoring mode at m/z 500.2 -> 221.2 for fimasartan and m/z 524.3 -> 204.9 for
      the IS. The assay was linear over a calibration range of 0.5-500 ng/mL with a
      lower limit of quantification of 0.5 ng/mL. The coefficient of variation of this
      assay precision was <14.9% and the accuracy exceeded 91.9%. This method provided
      the necessary sensitivity, linearity, precision, accuracy and specificity to
      allow the determination of fimasartan after oral administration to healthy Korean
      male volunteers in several drug-drug interaction studies conducted at the
      Clinical Trials Center of Seoul National University Hospital. 

PMID- 25616989
TI  - Simultaneous quantification of related substances of perindopril tert-butylamine
      using a novel stability indicating liquid chromatographic method.
AB  - A novel stability indicating gradient reverse-phased high-performance liquid
      chromatographic method has been developed for the quantification of impurities of
      perindopril tert-butylamine (PER) in pharmaceutical dosage form. Separation of
      the active substance and its known (Impurities B, C, D, E, F) and unknown
      impurities was achieved on a BDS Hypersil C18 column (250 mm * 4.6 mm, 5 um),
      thermostated at 70 degrees C, using a mobile phase comprised of aqueous solution
      of sodium 1-heptanesulfonate adjusted to pH 2 with perchloric acid and
      acetonitrile. The flow rate was maintained at 1.5 mL min(-1), injection volume of
      20 uL was utilized and detection of analytes was performed at 215 nm. The
      developed method was validated in accordance with current ICH Guidelines for all
      suggested parameters, including forced degradation studies and proved to be
      linear, accurate, precise and suitable for the impurity testing of PER, being
      subsequently applied during on-going stability studies of a newly developed
      generic formulation. 

PMID- 25616990
TI  - The Determination of Nitrate and Nitrite in Human Urine and Blood by High
      Performance Liquid Chromatography and Cloud-Point Extraction.
AB  - A simple efficient and practical separation/preconcentration coupled with HPLC
      method for the determination nitrate and low concentrations of nitrite in human
      urine and blood was investigated. The method is based on precolumn derivatization
      using the Griess reaction and cloud-point extraction (CPE) of nitrite anion and
      direct determination of nitrate using its UV absorbance by ion-pair HPLC. The
      chromatographic process with detection at two wavelengths (510 and 220 nm) allows
      the determination of nitrite and nitrate. Decolorization and protein
      precipitation of urine and blood was applied to overcome the interference of
      matrix and enhance the sensitivity. The method was validated for linearity,
      accuracy and precision. Under the optimum conditions, the linear range of nitrite
      from 10 to 1,000 ng/mL and nitrate from 0.1 to 10 ug/mL. Product recoveries
      ranged from 92.4 to 99.9%. The limits of detection were 1 ng/mL and 0.1 ug/mL for
      nitrite and nitrate, respectively. Therefore, the technique was simple and
      reliable, with potential application in biological sample analysis of nitrate and
      nitrite. 

PMID- 25616991
TI  - A novel active intraoral appliance for presurgical orthopaedic treatment in
      patients with complete bilateral cleft lip and palate.
AB  - BACKGROUND: Management of the protruding/deviated premaxilla in patients with
      complete bilateral cleft lip and palate is a challenging problem for surgeons and
      orthodontists. Various passive and active methods have been developed for the
      presurgical orthopaedic treatment. However, most of these treatments are
      complicated and laborious for the patient's parents and clinicians. Here, we
      describe our original active intraoral appliance comprising two components, that
      is, the premaxillary and palatine process plates, connected with two elastic
      chains, and we assess its therapeutic efficacy. PATIENTS AND METHODS: We
      retrospectively evaluated 15 patients treated using this appliance during 2006
      2012, followed up for an average of 60.3 months (range, 18-97 months). We
      analysed the cleft widths and maxillary size, obtained pretreatment, post
      treatment and pre-palatoplasty. RESULTS: Cleft widths and premaxillary protrusion
      were significantly decreased post treatment; however, the transverse dimensions
      were not significantly altered. In all cases, the protruding/deviated premaxilla
      was set into a suitable position within 1 month, and we could perform one-stage
      cheiloplasty using the modified Mulliken method with low tension. CONCLUSION: Our
      appliance is technically simple to use, less invasive to the skin and bone and
      cost-effective, with reliable and predictable outcomes. In the follow-up period,
      we observed no detrimental growth of the maxilla or dentition. Therefore, we
      consider our appliance to be useful for application in presurgical orthopaedic
      treatments of complete bilateral cleft lip and palate.

PMID- 25616992
TI  - Free conjoined or chimeric medial sural artery perforator flap for the
      reconstruction of multiple defects in hand.
AB  - BACKGROUND: One-stage coverage of multiple or jumping defects in the hand remains
      a great challenge in reconstructive surgery. A medial sural artery perforator
      based conjoined or chimeric flap can be a potential candidate for reconstruction
      and a versatile donor site for tendon and nerve grafts. METHODS: Between
      September 2009 and December 2012, two free conjoined and three free chimeric
      medial sural artery perforator flaps were transferred to reconstruct multiple
      soft tissue defects in the hands. Only patients with more than two perforators in
      the preoperative Doppler analysis were admitted to this surgical approach. The
      anatomy, surgical technique, and clinical follow-up for up to 24 months are
      described. RESULTS: A variation of two to four perforators was found during
      dissection. All the flaps survived completely, and one patient developed wound
      dehiscence, which healed after continuous dressing changes. Two patients received
      tendon and nerve grafts simultaneously. Three donor sites received an additional
      free skin graft from the groin region. Follow-up of the five patients ranged from
      6 to 24 months (mean 13 months) postoperatively. No obvious donor-site morbidity
      was observed. The patients were satisfied with the single-stage procedure and the
      aesthetic outcome of the hands. CONCLUSION: The free conjoined or chimeric medial
      sural artery perforator flap can provide a single-stage solution for multiple
      defects in the hand. The versatile donor site also provides the option to harvest
      a segment of a tendon or nerve graft for single-stage composite tissue
      reconstruction.

PMID- 25616993
TI  - Rejected epidemiologic manuscripts: food for thought.

PMID- 25616994
TI  - Combining apples and oranges obtains common features of fruit.

PMID- 25616995
TI  - Ketamine for the treatment of depression in patients receiving hospice care: a
      retrospective medical record review of thirty-one cases.
AB  - BACKGROUND: Depression is prevalent in patients receiving hospice care. Standard
      antidepressant medications do not work rapidly enough in this setting. Evidence
      suggests that ketamine rapidly treats treatment refractory depression in the
      general population. Ketamine's role for treating depression in the hospice
      population warrants further study. METHODS: A retrospective medical record review
      of 31 inpatients receiving hospice care who received ketamine for depression on a
      clinical basis was conducted. The primary outcome measure was the Clinical Global
      Impression Scale, which was used retrospectively to rate subjects' therapeutic
      improvement, global improvement, and side effects from ketamine over 21 days.
      Additionally, time to onset of therapeutic effect was analyzed. RESULTS: Using
      the Clinical Global Impression Scale, ketamine was found to be significantly
      therapeutically effective through the first week after ketamine dosing (p <
      0.05), with 93% of patients showing positive results for days 0-3 and 80% for
      days 4-7 following ketamine dosing. Patients experienced global improvement
      during all 4 studied time periods following ketamine dosing (p < 0.05).
      Significantly more patients had either no side effects or side effects that did
      not significantly impair functioning at each of the 4 assessed time periods
      following ketamine dosing (p < 0.05). Additionally, significantly more patients
      experienced their first therapeutic response during days 0-1 following ketamine
      dosing (p < 0.001) than during any other time period. CONCLUSIONS: These data
      suggest that ketamine may be a safe, effective, and rapid treatment for clinical
      depression in patients receiving hospice care. Blinded, randomized, and
      controlled trials are required to substantiate these findings and support further
      clinical use of this medication in hospice settings.

PMID- 25616996
TI  - [Recommendations of the updated LONTS guidelines. Long-term opioid therapy for
      chronic noncancer pain].
AB  - BACKGROUND: The regular update of the German S3 guidelines on long-term opioid
      therapy for chronic noncancer pain (CNCP), the"LONTS" (AWMF registration number
      145/003), began in November 2013. METHODS: The guidelines were developed by 26
      scientific societies and two patient self-help organisations under the
      coordination of the Deutsche Schmerzgesellschaft (German Pain Society). A
      systematic literature search in the Cochrane Central Register of Controlled
      Trials (CENTRAL), Medline and Scopus databases (up until October 2013) was
      performed. Levels of evidence were assigned according to the classification
      system of the Oxford Centre for Evidence-Based Medicine. The strength of the
      recommendations was established by multistep formal procedures, in order to reach
      a consensus according to German Association of the Medical Scientific Societies
      ("Arbeitsgemeinschaft der Wissenschaftlich Medizinischen Fachgesellschaften",
      AWMF) regulations. The guidelines were reviewed by the Drug Commission of the
      German Medical Association, the Austrian Pain Society and the Swiss Association
      for the Study of Pain. RESULTS: Opioids are one drug-based treatment option for
      short- (4-12 weeks), intermediate- (13-25 weeks) and long-term (>= 26 weeks)
      therapy of chronic osteoarthritis, diabetic polyneuropathy, postherpetic
      neuralgia and low back pain. Contraindications are primary headaches, as well as
      functional somatic syndromes and mental disorders with the (cardinal) symptom
      pain. For all other clinical presentations, a short- and long-term therapy with
      opioid-containing analgesics should be evaluated on an individual basis. Long
      term therapy with opioid-containing analgesics is associated with relevant risks
      (sexual disorders, increased mortality). CONCLUSION: Responsible application of
      opioid-containing analgesics requires consideration of possible indications and
      contraindications, as well as regular assessment of efficacy and adverse effects.
      Neither an uncritical increase in opioid application, nor the global rejection of
      opioid-containing analgesics is justified in patients with CNCP.

PMID- 25616997
TI  - [Perception of UCI nurses in relation with satisfactory care: convergences and
      divergences with the perception of critical patients].
AB  - OBJECTIVE: Explore convergences and divergences between perception of nurses and
      of critically ill patients, in relation to the satisfactory care given and
      received. METHODS: It is part of a larger qualitative study, according to the
      Grounded Theory. Carried out in 3 intensive care units with 34 boxes. Sampling
      theoretical profiles with n=19 patients and n=7 nurses after data saturation.
      Recruitment of patients included in the profiles of elderly and long-stay got
      stretched over some time due to the low incidence of cases. Data collection
      consisted of: in-depth interview to critically ill patients, group discussion of
      expert nurses in the critical care patient and field diary. Analysis themed on
      Grounded Theory according Strauss and Corbin: open coding, axial and selective.
      Analysis followed criteria of Guba and Lincoln rigor, Calderon quality and
      Gastaldo and McKeever ethical reflexivity. There was a favorable report from the
      ethical committee of the Hospital and informed consent of the participants.
      RESULTS: Four matching categories were found: professional skills, human,
      technical and continued care. Combination of these elements creates feelings of
      security, calmness and feeling like a person, allowing the patient a close and
      trusting relationship with the nurse who takes individualized care. Not divergent
      categories were found. CONCLUSIONS: Perceptions of nurses in relation to care
      match perceptions of critically ill patients in both the definition and
      dimensions upon satisfactory care.

PMID- 25616998
TI  - Proper genomic profiling of (BRCA1-mutated) basal-like breast carcinomas requires
      prior removal of tumor infiltrating lymphocytes.
AB  - INTRODUCTION: BRCA1-mutated breast carcinomas may have distinct biological
      features, suggesting the involvement of specific oncogenic pathways in tumor
      development. The identification of genomic aberrations characteristic for BRCA1
      mutated breast carcinomas could lead to a better understanding of BRCA1
      associated oncogenic events and could prove valuable in clinical testing for
      BRCA1-involvement in patients. METHODS: For this purpose, genomic and gene
      expression profiles of basal-like BRCA1-mutated breast tumors (n = 27) were
      compared with basal-like familial BRCAX (non-BRCA1/2/CHEK2*1100delC) tumors (n =
      14) in a familial cohort of 120 breast carcinomas. RESULTS: Genome wide copy
      number profiles of the BRCA1-mutated breast carcinomas in our data appeared
      heterogeneous. Gene expression analyses identified varying amounts of tumor
      infiltrating lymphocytes (TILs) as a major cause for this heterogeneity. Indeed,
      selecting tumors with relative low amounts of TILs, resulted in the
      identification of three known but also five previously unrecognized BRCA1
      associated copy number aberrations. Moreover, these aberrations occurred with
      high frequencies in the BRCA1-mutated tumor samples. Using these regions it was
      possible to discriminate BRCA1-mutated from BRCAX breast carcinomas, and they
      were validated in two independent cohorts. To further substantiate our findings,
      we used flow cytometry to isolate cancer cells from formalin-fixed, paraffin
      embedded, BRCA1-mutated triple negative breast carcinomas with estimated TIL
      percentages of 40% and higher. Genomic profiles of sorted and unsorted fractions
      were compared by shallow whole genome sequencing and confirm our findings.
      CONCLUSION: This study shows that genomic profiling of in particular basal-like,
      and thus BRCA1-mutated, breast carcinomas is severely affected by the presence of
      high numbers of TILs. Previous reports on genomic profiling of BRCA1-mutated
      breast carcinomas have largely neglected this. Therefore, our findings have
      direct consequences on the interpretation of published genomic data. Also, these
      findings could prove valuable in light of currently used genomic tools for
      assessing BRCA1-involvement in breast cancer patients and pathogenicity
      assessment of BRCA1 variants of unknown significance. The BRCA1-associated
      genomic aberrations identified in this study provide possible leads to a better
      understanding of BRCA1-associated oncogenesis.

PMID- 25616999
TI  - Identification of divergent WH2 motifs by HMM-HMM alignments.
AB  - BACKGROUND: The actin cytoskeleton is a hallmark of eukaryotic cells. Its
      regulation as well as its interaction with other proteins is carefully
      orchestrated by actin interaction domains. One of the key players is the WH2
      motif, which enables binding to actin monomers and filaments and is involved in
      the regulation of actin nucleation. Contrasting conserved domains, the
      identification of this motif in protein sequences is challenging, as it is short
      and poorly conserved. FINDINGS: To identify divergent members, we combined Hidden
      Markov-Model (HMM) to HMM alignments with orthology predictions. Thereby, we
      identified nearly 500 proteins containing so far not annotated WH2 motifs. This
      included shootin-1, an actin binding protein involved in neuron polarization.
      Among others, WH2 motifs of 'proximal to raf' (ptr)-orthologs, which are
      described in the literature, but not annotated in genome databases, were
      identified. CONCLUSION: In summary, we increased the number of WH2 motif
      containing proteins substantially. This identification of candidate regions for
      actin interaction could steer their experimental characterization. Furthermore,
      the approach outlined here can easily be adapted to the identification of
      divergent members of further domain families.

PMID- 25617000
TI  - Locus of Control Orientation: Parents, Peers, and Place.
AB  - An internal locus of control contributes to positive youth outcomes such as a
      general well-being and academic success, while also serving as a protective
      factor against exposure to community violence and reducing negative behaviors
      like violence. Despite these benefits, very little is known about antecedents of
      an internal locus of control orientation. Without an understanding of what
      factors contribute to the development of an internal locus of control, it is not
      clear how to best encourage its formation. This study uses data from the Project
      on Human Development in Chicago Neighborhoods to examine whether various
      mesosystem variables (family management strategies, peer interactions,
      neighborhood context, and individual-level characteristics) are associated with
      an internal locus of control orientation among 1,076 youth ages 9-19 living in 78
      Chicago neighborhoods. Study participants were Hispanic (46 %), African American
      (34 %), and White (15 %), and 50 % were female. The findings suggest that, while
      most levels of the mesosystem influence locus of control orientation, family
      management strategies are more prominent determinants of an internal locus of
      control than peers, neighborhood context, or individual characteristics. Parental
      supervision over the time a youth spends at home and family socioeconomic status
      are consistent predictors of an internal locus of control, while harsh discipline
      is associated with an external locus of control. The discussion examines the
      import of various parenting techniques in shaping an internal locus of control
      and considers future avenues for research to further unpack how antecedents of
      locus of control can vary across youth. 

PMID- 25617001
TI  - [Obstructive sleep apnea: CPAP versus oxygen: Heart Biomarker Evaluation in Apnea
      Treatment (HeartBEAT)].

PMID- 25617002
TI  - [Diabetes mellitus : A risk factor for stroke in women].

PMID- 25617003
TI  - [Snake bite in a 53-year-old female tourist].
AB  - Snake bites are rare events in Germany and are not life-threatening with usually
      only mild clinical symptoms. The most widespread venomous snake is the common
      European adder (Vipera berus). Here we present the case of a 53-year-old woman
      who was bitten by a common adder. Although the patient was initially in stable
      condition she developed edematous swelling of the complete lower limb,
      subcutaneous bleeding, and rhabdomyolysis. The aim of this report is to raise
      awareness that even in a central European country like Germany snake bites with a
      life-threatening course can occur and need immediate attention and medical care. 

PMID- 25617004
TI  - Response.

PMID- 25617005
TI  - Whole exome sequencing identifies three recessive FIG4-mutations in an apparently
      dominant pedigree with Charcot-Marie-Tooth disease.

PMID- 25617007
TI  - Low specificity of 2 tetanus rapid tests in Cambodia.
AB  - OBJECTIVES: Rapid testing for tetanus on serum or blood allows for an immediate
      evaluation of individual protection against tetanus in developed countries, using
      a "single step" immunochromatographic technique using tetanus toxoid. The
      specificity of these tests, compared to the reference method for tetanus, mouse
      serum neutralization testing, has however never been assessed in these countries,
      due to the difficulty to perform serum neutralization titration in mice, because
      of animal testing bioethical regulations. POPULATION AND METHODS: A collection of
      sera from adult volunteers in Cambodia, living in rural environment, was tested
      for tetanus antibodies by ELISA in France, and by mouse serum neutralization in
      Vietnam. This allowed estimating the sensitivity and specificity of 2 rapid
      tetanus tests, available on the market: TQSTM and TetanotopTM. RESULTS: The
      sensitivity of these tests was adequate, compared to mice serum neutralization
      test, for a test threshold of 0.01 IU/mL, (100% for TQSTM, 91% for TetanotopTM),
      but their specificity was very low (1% for TQSTM and 13% for TetanotopTM).
      CONCLUSION: The results prove that these rapid tests for the assessment of
      individual protection against tetanus should not be used in the adult rural
      Cambodian population.

PMID- 25617008
TI  - Systematic review of autogenous osteochondral transplant outcomes.
AB  - PURPOSE: The goal of this systematic review was to present the current best
      evidence for clinical outcomes of osteochondral autograft transplantation to
      elucidate the efficacy of this procedure. METHODS: PubMed, CINAHL, and the
      Cochrane Central Register of Controlled Trials were searched (key terms "knee,"
      "osteochondral autograft transfer," or "mosaicplasty") to identify relevant
      literature between 1950 and 2013 in the English language. This evaluation
      included studies in pediatric and adult patients with grade 3 or 4 articular
      cartilage injuries; the studies had a minimum of 25 patients and at least 12
      months of follow-up and compared osteochondral autograft transfers/mosiacplasty
      with another treatment modality. Articles were limited to full-text randomized
      controlled trials or cohort studies. Main outcomes studied were patient-reported
      and functional outcome, with secondary outcomes including effect of lesion size,
      return to sport and sport function, radiographic outcomes, and reoperation rates.
      RESULTS: There were a total of 9 studies with 607 patients studied in this
      systematic review. When osteochondral autologous transfer/mosaicplasty (OATM) was
      compared with microfracture (MF), patients with OATM had better clinical results,
      with a higher rate of return to sport and maintenance of their sports function
      from before surgery. Meanwhile, patients who underwent MF trended toward more
      reoperations, with deterioration around 4 years after surgery. When compared with
      autologous chondrocyte implantation (ACI), clinical outcome improvement was not
      conclusive; however, at 10-year follow-up, a greater failure rate was found to be
      present in the OATM group. CONCLUSIONS: Current evidence shows improved clinical
      outcomes with OATM when compared with preoperative conditions. These patients
      were able to return to sport as early as 6 months after the procedure. It could
      be suggested from the data that OATM procedures might be more appropriate for
      lesions that are smaller than 2 cm(2) with the known risk of failure between 2
      and 4 years. Further high-quality prospective studies into the management of
      these articular cartilage injuries are necessary to provide a better framework
      within which to target intervention. LEVEL OF EVIDENCE: Level II, systematic
      review of Level I and II studies.

PMID- 25617006
TI  - Targeted sequencing and identification of genetic variants in sporadic inclusion
      body myositis.
AB  - Sporadic inclusion body myositis (sIBM) has clinical, pathologic and
      pathomechanistic overlap with some inherited muscle and neurodegenerative
      disorders. In this study, DNA from 79 patients with sIBM was collected and the
      sequencing of 38 genes associated with hereditary inclusion body myopathy (IBM),
      myofibrillar myopathy, Emery-Dreifuss muscular dystrophy, distal myopathy,
      amyotrophic lateral sclerosis and dementia along with C9orf72 hexanucleotide
      repeat analysis was performed. No C9orf72 repeat expansions were identified, but;
      27 rare (minor allele frequency <1%) missense coding variants in several other
      genes were identified. One patient carried a p.R95C missense mutation in VCP and
      another carried a previously reported p.I27V missense mutation in VCP. Mutations
      in VCP cause IBM associated with Paget's disease of the bone (PDB) and fronto
      temporal dementia (IBMPFD). Neither patient had a family history of weakness or
      manifested other symptoms reported with VCP mutations such as PDB or dementia. In
      vitro analysis of these VCP variants found that they both disrupted autophagy
      similar to other pathogenic mutations. Although no clear genetic etiology has
      been implicated in sIBM pathogenesis, our study suggests that genetic evaluation
      in sIBM may be clinically meaningful and lend insight into its pathomechanism. 

PMID- 25617009
TI  - Chronic Stress and Adolescents' Mental Health: Modifying Effects of Basal
      Cortisol and Parental Psychiatric History. The TRAILS Study.
AB  - Large individual differences in adolescent mental health following chronic
      psychosocial stress suggest moderating factors. We examined two established
      moderators, basal cortisol and parental psychiatric history, simultaneously. We
      hypothesized that individuals with high basal cortisol, assumed to indicate high
      context sensitivity, would show relatively high problem levels following chronic
      stress, especially in the presence of parental psychiatric history. With Linear
      Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2%
      boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the
      absence of a parental psychiatric history increased the risk of externalizing but
      not internalizing problems following chronic stress. Conversely, low basal
      cortisol combined with a substantial parental psychiatric history increased the
      risk of internalizing but not externalizing problems following chronic stress.
      Thus, parental psychiatric history moderated stress- cortisol interactions in
      predicting psychopathology, but in a different direction than hypothesized. We
      conclude that the premise that basal cortisol indicates context sensitivity may
      be too crude. Context sensitivity may not be a general trait but may depend on
      the nature of the context (e.g., type or duration of stress exposure) and on the
      outcome of interest (e.g., internalizing vs. externalizing problems). Although
      consistent across informants, our findings need replication.

PMID- 25617010
TI  - Homosexuality-related stigma and sexual risk behaviors among men who have sex
      with men in Hanoi, Vietnam.
AB  - This article examined the associations between three forms of homosexuality
      related stigma (enacted, perceived, and internalized homosexual stigmas) with
      risky sexual behaviors, and to describe the mechanisms of these associations,
      among men who have sex with men (MSM) in Hanoi, Vietnam. We used respondent
      driven sampling (RDS) to recruit 451 MSM into a cross-sectional study conducted
      from August 2010 to January 2011. Data were adjusted for recruitment patterns due
      to the RDS approach; logistic regression and path analyses were performed.
      Participants were young and single; most had attended at least some college. Nine
      out of ten participants engaged in sexual behaviors at moderate to high risk
      levels. Compared to those who had no enacted homosexual stigma, men having low
      and high levels of enacted homosexual stigma, respectively, were 2.23 times (95 %
      CI 1.35-3.69) and 2.20 times (95 % CI 1.04-4.76) more likely to engage in high
      levels of sexual risk behaviors. In addition, there was an indirect effect of
      perceived homosexual stigma and internalized homosexual stigma on sexual risk
      behaviors through depression and drug and alcohol use. Our study provides
      valuable information to our understanding of homosexual stigma in Vietnam,
      highlighting the need for provision of coping skills against stigma to the gay
      community and addressing drinking and drug use among MSM, to improve the current
      HIV prevention interventions in Vietnam. 

PMID- 25617011
TI  - Sex work among students of higher education: a survey-based, cross-sectional
      study.

PMID- 25617012
TI  - Annual Congress of the European Society of Cardiology: Aug 30-Sept 3 2014;
      Barcelona, Spain.

PMID- 25617013
TI  - Review of thalidomide use in the pediatric population.
AB  - Thalidomide is resurging in the management of adult rheumatologic skin
      conditions, especially lupus erythematosus. Although use in pediatric patients is
      reported since the 1990s, there are no systematic reviews describing treatment in
      children. Thalidomide has immunomodulatory and anti-tumor necrosis factor-alpha
      effects as well as antiangiogenic properties, making it useful for a broad
      spectrum of inflammatory disorders. Thalidomide is second-line treatment for
      aphthous stomatitis and chronic graft-versus-host disease in children and has
      been prescribed for many other conditions including actinic prurigo and
      epidermolysis bullosa pruriginosa. Systemic lupus erythematosus may be less
      responsive to thalidomide in children than adults. Peripheral neuropathy is
      observed in both idiosyncratic and dose-dependent relationships; children older
      than 12 years may be more susceptible to developing this adverse effect than
      younger patients. There are rare reports of thrombotic complications in children
      treated for nonmalignant indications. We review the mechanism of action and
      propose that thalidomide is an alternative treatment for patients who fail or
      have contraindications to anti-tumor necrosis factor-alpha biologics. 

PMID- 25617014
TI  - Cutaneous borreliosis associated with T cell-predominant infiltrates: a
      diagnostic challenge.
AB  - BACKGROUND: With the exception of erythema migrans, Borrelia infection of the
      skin manifests much more commonly with B cell-rich infiltrates. T cell-rich
      lesions have rarely been described. OBJECTIVE: We report a series of 6 patients
      with cutaneous borreliosis presenting with T cell-predominant skin infiltrates.
      METHODS: We studied the clinicopathologic and molecular features of 6 patients
      with T cell-rich skin infiltrates. RESULTS: Half of the patients had erythematous
      patchy, partly annular lesions, and the other patients had features of
      acrodermatitis chronica atrophicans. Histopathology revealed a dense, band-like
      or diffuse dermal infiltrate. Apart from small, well differentiated lymphocytes,
      there were medium-sized lymphocytes with slight nuclear atypia and focal
      epidermotropism. An interstitial histiocytic component was found in 4 cases,
      including histiocytic pseudorosettes. Fibrosis was present in all cases but
      varied in severity and distribution. In 5 patients, borrelia DNA was detected in
      lesional tissue using polymerase chain reaction studies. No monoclonal
      rearrangement of T-cell receptor gamma genes was found. LIMITATIONS: This
      retrospective study was limited by the small number of patients. CONCLUSION: In
      addition to unusual clinical presentation, cutaneous borreliosis can
      histopathologically manifest with a T cell-rich infiltrate mimicking cutaneous T
      cell lymphoma. Awareness of this clinicopathologic constellation is important to
      prevent underrecognition of this rare and unusual presentation representing a
      Borrelia-associated T-cell pseudolymphoma.

PMID- 25617015
TI  - Clinical safety of England's national programme for IT: a retrospective analysis
      of all reported safety events 2005 to 2011.
AB  - OBJECTIVE: To analyse patient safety events associated with England's national
      programme for IT (NPfIT). METHODS: Retrospective analysis of all safety events
      managed by a dedicated IT safety team between September 2005 and November 2011
      was undertaken. Events were reviewed against an existing classification for
      problems associated with IT. The proportion of reported events per problem type,
      consequences, source of report, resolution within 24h, time of day and day of
      week were examined. Sub-group analyses were undertaken for events involving
      patient harm and those that occurred on a large scale. RESULTS: Of the 850 events
      analysed, 68% (n=574) described potentially hazardous circumstances, 24% (n=205)
      had an observable impact on care delivery, 4% (n=36) were a near miss, and 3%
      (n=22) were associated with patient harm, including three deaths (0.35%). Eleven
      events did not have a noticeable consequence (1%) and two were complaints (<1%).
      Amongst the events 1606 separate contributing problems were identified. Of these
      92% were predominately associated with technical rather than human factors.
      Problems involving human factors were four times as likely to result in patient
      harm than technical problems (25% versus 8%; OR 3.98, 95%CI 1.90-8.34). Large
      scale events affecting 10 or more individuals or multiple IT systems accounted
      for 23% (n=191) of the sample and were significantly more likely to result in a
      near miss (6% versus 4%) or impact the delivery of care (39% versus 20%;
      p<0.001). CONCLUSION: Events associated with NPfIT reinforce that the use of IT
      does create hazardous circumstances and can lead to patient harm or death. Large
      scale patient safety events have the potential to affect many patients and
      clinicians, and this suggests that addressing them should be a priority for all
      major IT implementations.

PMID- 25617016
TI  - The social licence for research: why care.data ran into trouble.
AB  - In this article we draw on the concept of a social licence to explain public
      concern at the introduction of care.data, a recent English initiative designed to
      extract data from primary care medical records for commissioning and other
      purposes, including research. The concept of a social licence describes how the
      expectations of society regarding some activities may go beyond compliance with
      the requirements of formal regulation; those who do not fulfil the conditions for
      the social licence (even if formally compliant) may experience ongoing challenge
      and contestation. Previous work suggests that people's cooperation with specific
      research studies depends on their perceptions that their participation is
      voluntary and is governed by values of reciprocity, non-exploitation and service
      of the public good. When these conditions are not seen to obtain, threats to the
      social licence for research may emerge. We propose that care.data failed to
      adequately secure a social licence because of: (i) defects in the warrants of
      trust provided for care.data, (ii) the implied rupture in the traditional role,
      expectations and duties of general practitioners, and (iii) uncertainty about the
      status of care.data as a public good. The concept of a social licence may be
      useful in explaining the specifics of care.data, and also in reinforcing the more
      general lesson for policy-makers that legal authority does not necessarily
      command social legitimacy. 

PMID- 25617017
TI  - Vertebral osteomyelitis secondary to a S. schleiferi infection from a cardiac
      defibrillator.

PMID- 25617018
TI  - [Prevalence of nasal carriage of Staphylococcus aureus and Streptococcus
      pneumoniae in Primary Care and factors associated with colonization].
AB  - OBJECTIVE: To determine (i) the prevalence of Staphylococcus aureus (S.aureus)
      and Streptococcus pneumoniae (S.pneumoniae) nasal carriage in Primary Health Care
      patients in area of Barcelona, and (ii) the factors associated with S.aureus and
      S.pneumoniae colonization. METHODS: Multi-center cross-sectional study conducted
      in 2010-2011 with the participation of 27 Primary Health Care professionals.
      Nasopharyngeal swabs were obtained from 3,969 patients over 4 years of age who
      did not present with any sign of infection. DEPENDENT VARIABLES: S.aureus and/or
      S.pneumoniae carrier state. INDEPENDENT VARIABLES: socio-demographic
      characteristics, health status, vaccination status, occupation, and living with
      children. A descriptive analysis was performed. The prevalence of carriers of
      S.aureus and/or S.pneumoniae was calculated and logistic regression models were
      adjusted by age. RESULTS: In children from 4 to 14 years old, the prevalence of
      S.aureus carriers was 35.7%, of S.pneumoniae 27.1%, and 5.8% were co-colonized.
      In adults older than 14 years old, the prevalence was 17.8%, 3.5%, and 0.5%,
      respectively. In children, S.aureus carrier state was inversely associated with
      S.pneumoniae carrier state; S.pneumoniae was associated with younger age, and
      inversely associated with S.aureus carrier state. In adults, being a carrier of
      S.aureus was associated with male gender, younger age, and a health-related
      occupation, whereas S.pneumoniae carrier state was associated with living with
      children under 6 years of age. The proportion of co-colonized carriers was low
      (1.0%). CONCLUSIONS: The proportion of S.aureus and S.pneumoniae carriers was
      higher in children than in adults. Age was the only factor associated with
      healthy carrier status for S.aureus and for S.pneumoniae.

PMID- 25617020
TI  - Donald F. Steiner, MD, 1930-2014: pioneering diabetes researcher.

PMID- 25617019
TI  - Happy Birthday EASD--50 years of dedication to diabetes research.

PMID- 25617021
TI  - Sliding of the load carrier in third-generation intramedullary nails for proximal
      femur fractures: an in vitro mechanical comparison study.
AB  - Dynamic osteosynthesis of proximal femur fractures facilitates compression at the
      fracture site through distal glide of the femoral head load carrier in the
      intramedullary nail. Modern implants are currently designed according to diverse
      gliding principles. The aim of this study was to compare the sliding mechanisms
      of different types of nails. As in other similar mechanical studies the load
      patterns occurring around the femoral head load carrier and the intramedullary
      nail under full load were simulated for three different types of intramedullary
      nail - PFNA, Targon PFT and Trigen Intertan. The load necessary to trigger distal
      displacement of the femoral head implant in the nail was determined. The lengths
      of the load carriers were varied. For the three lengths of load carrier,
      mechanical testing showed that the Targon PFT started to slide at a significantly
      lower load compared to the other two implants. Comparison of the PFNA and Trigen
      Intertan in terms of load to dynamization for 77 mm carriers revealed a
      significantly lower load for the PFNA. Slide efficacy for the PFNA and the Trigen
      Intertan was found to improve as the length of the blade/screw was shortened. The
      dynamization properties of the Targon PFT with its cylindrical sliding mechanism,
      similar to the DHS, were far better compared to the PFNA and the Trigen Intertan
      that have more complex sliding actions. Since theoretical considerations indicate
      that a less efficient gliding action leads to a higher complication rate,
      implants of the next generation should be optimized in this regard. 

PMID- 25617022
TI  - Phylogenetic relationships of Petrocoptis A. Braun ex Endl. (Caryophyllaceae), a
      discussed genus from the Iberian Peninsula.
AB  - Petrocoptis is a small genus of chasmophytic plants endemic to the Iberian
      Peninsula, with some localized populations in the French Pyrenees. Within the
      genus, a dozen species have been recognized based on morphological diversity,
      most of them with limited distribution area, in small populations and frequently
      with potential threats to their survival. To date, however, a molecular
      evaluation of the current systematic treatments has not been carried out. The aim
      of the present study is to infer phylogenetic relationships among its subordinate
      taxa by using plastidial rps16 intron and nuclear internal transcribed spacer
      (ITS) DNA sequences; and evaluate the phylogenetic placement of the genus
      Petrocoptis within the family Caryophyllaceae. The monophyly of Petrocoptis is
      supported by both ITS and rps16 intron sequence analyses. Furthermore, time
      estimates using BEAST analyses indicate a Middle to Late Miocene diversification
      (10.59 Myr, 6.44-15.26 Myr highest posterior densities [HPD], for ITS; 14.30 Myr,
      8.61-21.00 Myr HPD, for rps16 intron).

PMID- 25617023
TI  - Asynchronous ovulation in mares: seasonal variations in frequency.
AB  - The mare's reproductive system is rarely capable of sustaining multiple
      pregnancies to term. Multiple pregnancies largely derive from multiple
      ovulations, most commonly double ovulations, hence, double ovulations are of
      significant concern to breeders/veterinarians. Double ovulations may be
      synchronous or asynchronous. Asynchrony of up to 96 hours may result in two
      embryonic vesicles of very different sizes, which are challenging to detect at
      early ultrasonic pregnancy detection. This study aims to (1) document the
      incidence of synchronous and asynchronous double ovulation and (2) determine
      whether this varies with month/season. 506 cycles from double ovulating mares
      were monitored at 8+/-1 hour intervals before expected ovulation until 96 hours
      post initial ovulation. Mares were grouped according to eight-hour ovulation
      intervals and month/season. When asynchrony was classed as greater than or equal
      to eight hours or greater than or equal to 24 hours apart, respectively, a
      significant (P<0.001) difference existed between the number of mares
      demonstrating asynchronous double ovulations (65.8 and 28.5 per cent) and
      synchronous double ovulations (34.2 and 71.5 per cent). Significantly (P<0.05),
      more asynchronous ovulations occurred in the seasonal transition periods. This
      study demonstrates that asynchronous double ovulation is common and emphasises
      the importance of closely monitoring mares, particularly at the extremes of the
      breeding season, for double ovulation up to or at 96 hours postinitial ovulation
      in order to minimise the chances of missing multiple pregnancy. 

PMID- 25617024
TI  - Prefrontal cortical dopamine from an evolutionary perspective.
AB  - In this article, we propose the hypothesis that the prefrontal cortex (PFC)
      acquired neotenic development as a consequence of mesocortical dopamine (DA)
      innervation, which in turn drove evolution of the PFC into becoming a complex
      functional system. Accordingly, from the evolutionary perspective, decreased DA
      signaling in the PFC associated with such adverse conditions as chronic stress
      may be considered as an environmental adaptation strategy. Psychiatric disorders
      such as schizophrenia and attention deficit/hyperactivity disorder may also be
      understood as environmental adaptation or a by-product of such a process that has
      emerged through evolution in humans. To investigate the evolutionary perspective
      of DA signaling in the PFC, domestic animals such as dogs may be a useful model. 

PMID- 25617025
TI  - Assessment of residual alveolar bone volume in hemodialysis patients using CBCT.
AB  - BACKGROUND: The study aims to assess the residual alveolar bone volume in Chinese
      chronic kidney disease (CKD) patients undergoing hemodialysis (HD) using cone
      beam computed tomography (CBCT). MATERIALS AND METHODS: Two hundred and eight HD
      patients and healthy controls were enrolled to undergo CBCT examination. To
      evaluate residual alveolar bone volume, bone height was measured from the
      alveolar crest (AC) to the maxillary sinus floor or the mandibular nerve canal,
      whereas bone width was measured at a depth of 1.0, 3.0, and 6.0 mm apical to the
      AC. RESULTS: There was no significant difference in demographics and the extent
      of tooth loss between HD patients and control group. Both groups showed abundant
      residual bone volume. However, the heights of residual alveolar bone at the upper
      premolars and first molar in HD patients were significantly lower than those of
      the control group (p < 0.05). No significant difference was observed for alveolar
      bone at the lower premolars and molars. The bone width showed statistical
      differences for HD patients' upper second molars, lower first premolars, and
      second molars (p < 0.05). CONCLUSIONS: While the residual bone was sufficient for
      implant placement, HD patients exhibited with significantly lower residual bone
      height at the sites of the upper premolars and first molar and varied residual
      bone width depending on the location. CLINICAL RELEVANCE: Owing to these changes,
      special cautions need to be taken for patients undergoing HD or with chronically
      impaired renal functions during implant treatment planning.

PMID- 25617026
TI  - Comparison between three different saliva substitutes in patients with
      hyposalivation.
AB  - OBJECTIVE: The aim of the present study was to compare the efficiency of oral
      spray based on thermal spring water (Buccotherm(r)) versus commercial saliva
      substitute (Xeros(r)) and marshmallow root on the quality of life in patients
      with hyposalivation. MATERIALS AND METHODS: A total of 60 patients with
      unstimulated salivary flow rate <0.2 ml/min were randomized into three groups. In
      the first group, 30 patients were using Buccotherm(r); in the second group, 15
      patients were using Xeros(r); and in the third group, 15 patients were using
      marshmallow root. Therapy lasted for 2 weeks; everyday, patients used one of the
      products four times a day. Quality of life was measured by the Croatian version
      of Oral Health Impact Profile 14 questionnaire, and visual analog scale was used
      to determine the intensity of dry mouth before and after therapy. Statistical
      analysis was performed by Wilcoxon signed-rank test and Kruskal-Wallis test.
      Standardized effect size was calculated for OHIP following treatment. RESULTS:
      Buccotherm(r) has shown the biggest effect on quality of life in patients with
      hyposalivation. Intensity of dry mouth was lower after the applied therapy
      whatever substitute patients used. CONCLUSIONS: We recommend the use of all three
      saliva substitutes for decreasing the intensity of dry mouth symptoms as well as
      improvement in the quality of life. CLINICAL RELEVANCE: Although all tested
      agents showed beneficial effect in alleviating hyposalivation symptoms, it seems
      that Buccotherm(r) was superior to Xeros(r) and marshmallow root.

PMID- 25617027
TI  - Microengineered liver tissues for drug testing.
AB  - Drug-induced liver injury (DILI) is a leading cause of drug attrition.
      Significant and well-documented differences between animals and humans in liver
      pathways now necessitate the use of human-relevant in vitro liver models for
      testing new chemical entities during preclinical drug development. Consequently,
      several human liver models with various levels of in vivo-like complexity have
      been developed for assessment of drug metabolism, toxicity, and efficacy on liver
      diseases. Recent trends leverage engineering tools, such as those adapted from
      the semiconductor industry, to enable precise control over the microenvironment
      of liver cells and to allow for miniaturization into formats amenable for higher
      throughput drug screening. Integration of liver models into organs-on-a-chip
      devices, permitting crosstalk between tissue types, is actively being pursued to
      obtain a systems-level understanding of drug effects. Here, we review the major
      trends, challenges, and opportunities associated with development and
      implementation of engineered liver models created from primary cells, cell lines,
      and stem cell-derived hepatocyte-like cells. We also present key applications
      where such models are currently making an impact and highlight areas for
      improvement. In the future, engineered liver models will prove useful for
      selecting drugs that are efficacious, safer, and, in some cases, personalized for
      specific patient populations. 

PMID- 25617029
TI  - Late gadolinium enhancement identified with cardiac magnetic resonance imaging in
      sarcoidosis patients is associated with long-term ventricular arrhythmia and
      sudden cardiac death.
AB  - AIMS: Cardiac involvement with sarcoidosis is a major cause of morbidity and
      mortality in affected individuals. Cardiac magnetic resonance (CMR) imaging
      promises a new and more accurate assessment of cardiac sarcoidosis by identifying
      typical patterns of myocardial fibrosis. We assessed the utility of CMR in the
      prediction of adverse outcomes. METHODS AND RESULTS: One hundred and six CMR
      patients with biopsy-proven extracardiac and/or presumed cardiac sarcoidosis were
      enrolled. Late gadolinium enhancement (LGE) on CMR typical of sarcoidosis was
      used to determine the presence of cardiac involvement. Clinical endpoints and
      medical records were assessed and those with implantable cardioverter
      defibrillators (ICDs) underwent device interrogation. Survival rates of patients
      with cardiac sarcoidosis were compared with those with only extracardiac disease.
      CMR identified 32 (30%) individuals as having cardiac sarcoidosis; the remaining
      74 (70%) had only extracardiac disease. At a mean follow-up time of 36.8 +/- 20.5
      months, patients with cardiac sarcoidosis had a higher rate of the composite
      cardiac endpoint--comprising sudden cardiac death (SCD) and ventricular
      tachyarrhythmia--compared with those with only extracardiac disease (P < 0.001).
      There was a higher rate of SCD or ICD-aborted SCD in patients with cardiac
      sarcoidosis vs. those without (P = 0.005). In patients with cardiac sarcoidosis,
      the rate of SCD was lower in those with an ICD compared with those without (P <
      0.02). CONCLUSIONS: Patients with evidence of cardiac sarcoidosis on CMR have
      higher rates of adverse cardiovascular events than those with only extracardiac
      disease. In patients with sarcoidosis detected on CMR, the presence of an ICD is
      associated with a lower rate of SCD.

PMID- 25617028
TI  - The relation between atrial septal defect shape, diameter, and area using three
      dimensional transoesophageal echocardiography and balloon sizing during
      percutaneous closure in children.
AB  - BACKGROUND: A trans-catheter closure of an atrial septal defect (ASD) is
      efficient. Balloon sizing (BS) during the catheterization leads to an
      overestimation of ASD size. Three-dimensional transoesophageal echocardiography
      (3D-TEE) allows the ASD morphology to be assessed comprehensively. The aim of
      this study was to assess the relationships between the shape and the measurements
      of ASDs by 2D-, 3D-TEE, and BS in children. METHODS AND RESULTS: Thirty children
      who underwent percutaneous closures of a single ASD were enrolled. ASD diameters
      were measured by 2D-transthoracic echocardiography (TTE), 2D-TEE, 3D-TEE and
      compared with BS. The ASD area was measured on 3D-TEE images after multi-planar
      reconstruction. ASD was estimated as round or oval on 3D-TEE 'en-face' view. 2D
      TTE, 2D-TEE, and 3D-TEE(max) ASD diameters were well correlated with BS (r =
      0.75; 0.80, and 0.85, respectively). Mean diameters were all significantly
      smaller than the mean BS. The mean difference between the balloon area and 3D-TEE
      area was 1.6 +/- 1.4 cm(2) (P < 0.0001). The mean difference between BS and 3D
      TEE(max) diameters was higher in round ASDs than in oval ASDs (4.0 +/- 3.3 vs.
      1.1 +/- 3.3, P = 0.02). With multivariate linear regression analysis, two
      formulas were built to predict BS. The first model was BS = 1.07 * 3D-TEE(max)-
      3.1 * ASDshape + 3. The ASD shape was 0 for round and 1 for oval ASDs. A second
      model was BS = 4.5 * ASDarea + 11.5. CONCLUSION: The ASD shape is accurately
      estimated by 3D-TEE and influences the relationship between echocardiographic
      measurements and BS. The ASD shape, its maximal diameter and the area assessed by
      3D-TEE may be sufficient to determine the device size without BS in children.

PMID- 25617030
TI  - Nuclear cardiology core syllabus of the European Association of Cardiovascular
      Imaging (EACVI).
AB  - The European Association of Cardiovascular Imaging (EACVI) Core Syllabus for
      Nuclear Cardiology is now available online. The syllabus lists key elements of
      knowledge in nuclear cardiology. It represents a framework for the development of
      training curricula and provides expected knowledge-based learning outcomes to the
      nuclear cardiology trainees.

PMID- 25617031
TI  - The mitral valve is an actively adapting tissue: new imaging evidence.

PMID- 25617032
TI  - Conceptualizing violence for health and medical geography.
AB  - Despite the fact that violence is a major threat to public health, the term
      itself is rarely considered as a phenomenon unto itself, and rarely figures
      explicitly in work by health and medical geographers. In response, I propose a
      definitionally and conceptually more robust approach to violence using a
      tripartite frame (interpersonal violence, structural violence, mass intentional
      violence) and suggest critical interventions through which to apply this more
      explicit and conceptually more robust approach: violence and embodiment via
      substance abuse in health geography, and structural violence via mental illness
      in medical geography. 

PMID- 25617033
TI  - Should age-period-cohort studies return to the methodologies of the 1970s?
AB  - Social scientists have recognized the importance of age-period-cohort (APC)
      models for half a century, but have spent much of this time mired in debates
      about the feasibility of APC methods. Recently, a new class of APC methods based
      on modern statistical knowledge has emerged, offering potential solutions. In
      2009, Reither, Hauser and Yang used one of these new methods - hierarchical APC
      (HAPC) modeling - to study how birth cohorts may have contributed to the U.S.
      obesity epidemic. They found that recent birth cohorts experience higher odds of
      obesity than their predecessors, but that ubiquitous period-based changes are
      primarily responsible for the rising prevalence of obesity. Although these
      findings have been replicated elsewhere, recent commentaries by Bell and Jones
      call them into question - along with the new class of APC methods. Specifically,
      Bell and Jones claim that new APC methods do not adequately address model
      identification and suggest that "solid theory" is often sufficient to remove one
      of the three temporal dimensions from empirical consideration. They also present
      a series of simulation models that purportedly show how the HAPC models estimated
      by Reither et al. (2009) could have produced misleading results. However, these
      simulation models rest on assumptions that there were no period effects, and
      associations between period and cohort variables and the outcome were perfectly
      linear. Those are conditions under which APC models should never be used. Under
      more tenable assumptions, our own simulations show that HAPC methods perform
      well, both in recovering the main findings presented by Reither et al. (2009) and
      the results reported by Bell and Jones. We also respond to critiques about model
      identification and theoretically-imposed constraints, finding little pragmatic
      support for such arguments. We conclude by encouraging social scientists to move
      beyond the debates of the 1970s and toward a deeper appreciation for modern APC
      methodologies.

PMID- 25617034
TI  - A rare case of primary high-grade large B-cell lymphoma of the sciatic nerve.

PMID- 25617035
TI  - Connect MM Registry: The Importance of Establishing Baseline Disease
      Characteristics.
AB  - BACKGROUND: Connect MM is the first and largest observational, noninterventional,
      prospective registry of patients newly diagnosed with multiple myeloma (NDMM) in
      the United States. It collects longitudinal data on patients within clinical
      practice including patients in clinical trials. PATIENTS AND METHODS: Of the 1513
      patients enrolled, 1493 were protocol-eligible. RESULTS: Median age was 67 years,
      81.9% (1223/1493) were Caucasian, and 57.2% (854/1493) were male. Of these
      patients, 26.5% (232/877) were International Staging System stage I, 34.9%
      (306/877) stage II, and 38.7% (339/877) stage III. Eastern Cooperative Oncology
      Group performance status of 0/1/2 were reported in 96.6% (1017/1053). Clonal
      plasma cells > 10% were found in 91.6% (1282/1399) of patients and M-component in
      98.8% (1343/1359). Hypercalcemia was present in 7.3% (108/1481) of patients,
      serum creatinine > 2 mg/dL in 18.3% (271/1484), anemia in 45.1% (673/1493), and
      bone involvement in 76.7% (1143/1490). Of the 15 National Comprehensive Cancer
      Network (NCCN) recommended diagnostic tests, a median of 12 were performed.
      Lactate dehydrogenase assessment, serum free light chain ratio, and
      immunofixation were reported in 38.4% (574/1493), 62.1% (927/1493), and 66%
      (985/1493) of patients, respectively. Quantitative immunoglobulin, beta-2
      microglobulin, and protein electrophoresis (serum or urine) were reported in
      72.3% (1080/1493), 74.1% (1107/1493), and 78.0% (1164/1493) of patients,
      respectively. Bone marrow biopsy was reported in 92.2% (1376/1493), but
      conventional cytogenetic and fluorescence in situ hybridization analysis were
      reported in only 63.2% (944/1493) and 59.8% (893/1493) of patients, respectively.
      A high-risk cytogenetic profile (according to International Myeloma Working Group
      [IMWG] criteria) was found in 16.9% (253/1493). CONCLUSION: This analysis
      provides insight into the demographic and disease characteristics of NDMM
      patients in a range of clinical practices. Creating solid records of baseline
      patient disease characteristics using suggested NCCN diagnostic work-up and IMWG
      criteria provides a foundation for monitoring disease progression and response to
      treatment.

PMID- 25617036
TI  - Current directions in military health-care provider resilience.
AB  - After more than a decade of war, the US military continues to place significant
      emphasis on psychological health and resilience. While research and programs that
      focus on the broader military community's resilience continue to emerge, less is
      known about and until recently little focus has been placed on military medical
      provider resilience. In this article, we review the literature on military
      medical provider resilience, provide an overview of the programmatic and
      technological advances designed to sustain and develop military medical provider
      resilience, and finally offer recommendations for future research. 

PMID- 25617037
TI  - The importance of anxiety states in bipolar disorder.
AB  - Anxiety symptoms and syndromes are common in bipolar disorders, occurring in over
      half of all subjects with bipolar disorder type I. Despite methodological and
      diagnostic inconsistencies, most studies have shown a robust association between
      the presence of a broadly defined comorbid anxiety disorder and important indices
      of clinical morbidity in bipolar disorder, including a greater number of
      depressive episodes, worse treatment outcomes, and elevated risk of attempting
      suicide. Anxiety symptoms and/or syndromes often precede the onset of bipolar
      disorder and may represent a clinical phenotype of increased risk in subjects
      with prodromal symptoms. Although the causal relationship between anxiety and
      bipolar disorders remains unresolved, the multifactorial nature of most
      psychiatric phenotypes suggests that even with progress towards more biologically
      valid phenotypes, the "phenomenon" of comorbidity is likely to remain a clinical
      reality. Treatment studies of bipolar patients with comorbid anxiety have begun
      to provide preliminary evidence for the role of specific pharmacological and
      psychotherapeutic treatments, but these need to be confirmed in more definitive
      trials. Hence, there is an immediate need for further research to help guide
      assessment and help identify appropriate treatments for comorbid conditions. 

PMID- 25617038
TI  - Late-life psychosis: diagnosis and treatment.
AB  - Psychosis is one of the most common conditions in later life with a lifetime risk
      of 23 %. Despite its high prevalence, late-onset psychosis remains a diagnostic
      and treatment dilemma. There are no reliable pathognomonic signs to distinguish
      primary or secondary psychosis. Primary psychosis is a diagnosis of exclusion and
      the clinician must rule out secondary causes. Approximately 60 % of older
      patients with newly incident psychosis have a secondary psychosis. In this
      article, we review current, evidence-based diagnostic and treatment approaches
      for this heterogeneous condition, emphasizing a thorough evaluation for the "six
      d's" of late-life psychosis (delirium, disease, drugs dementia, depression,
      delusions). Treatment is geared towards the specific cause of psychosis and
      tailored based on comorbid conditions. Frequently, environmental and psychosocial
      interventions are first-line treatments with the judicious use of pharmacotherapy
      as needed. There is an enormous gap between the prevalence of psychotic disorders
      in older adults and the availability of evidence-based treatment. The dramatic
      growth in the elderly population over the first half of this century creates a
      compelling need to address this gap.

PMID- 25617039
TI  - Predictors of the course of anxiety disorders in adolescents and young adults.
AB  - Anxiety disorders belong to the most frequent mental disorders and are often
      characterized by an early onset and a progressive, persistent/chronic, or
      recurrent course. Several individual, familial, and environmental risk factors
      for adverse course characteristics of anxiety disorders (including higher
      persistence, lower probability of remission, and increased risk of recurrence)
      have been identified, and previous research suggests that clinical features of
      anxiety (e.g., higher severity, duration, and avoidance) as well as comorbid
      other mental disorders are particularly useful for predicting an unfavorable
      course of anxiety disorders. However, additional studies are needed to identify
      risk factors for individual course trajectories of anxiety disorders in general
      as well as specific diagnoses. Doing so is essential in order to more precisely
      identify individuals with anxiety disorders who are at increased risk for adverse
      long-term outcomes and might thus particularly profit from targeted early
      interventions. 

PMID- 25617040
TI  - Anxiety and substance use disorders: co-occurrence and clinical issues.
AB  - The co-occurrence of substance use disorders (SUDs) and anxiety disorders has
      been now well established. This association is frequent and can be explained by
      three models: the shared vulnerability factors model, the self-medication model,
      and the substance-induced model. General population epidemiological studies
      provide strong evidence of the frequency of the association for the most used
      substances: tobacco, alcohol, cannabis, and to a lesser extent sedatives,
      opiates, and cocaine. For substances that are less commonly used in the general
      population, the frequency of the co-occurrence can more precisely be studied in
      clinical samples. We provide the most recent literature results on the
      association of SUDs and anxiety, and evidence for one explicative model or the
      other when available. For substances with sedative properties (alcohol,
      benzodiazepines, cannabis, opioids), both evidence for a self-medication and for
      a toxic effect exist. For substances with psychostimulant properties (tobacco,
      cocaine, and amphetamines), the literature favors the toxic hypothesis to explain
      the association with anxiety disorders. We give practical steps for the
      recognition of these dual diagnoses and present therapeutic issues, although the
      strategies are rarely evidence based. 

PMID- 25617041
TI  - Prenatal programming of mental illness: current understanding of relationship and
      mechanisms.
AB  - The British epidemiologist Dr. David J. Barker documented the relationship
      between infant birth weight and later onset of hypertension, coronary heart
      disease, insulin resistance, and type II diabetes. A stressful in utero
      environment can cause long-term consequences for offspring through prenatal
      programming. Prenatal programming most commonly occurs through epigenetic
      mechanisms and can be dependent on the type and timing of exposure as well as the
      sex of the fetus. In this review, we highlight the most recent evidence that
      prenatal programming is implicated in the development of psychiatric disorders in
      offspring exposed to maternal stress during pregnancy. Methodological differences
      between studies contribute to unavoidable heterogeneity in study findings.
      Current data suggest that fetal exposure to maternal hypothalamic-pituitary
      adrenal axis dysregulation, excessive glucocorticoids, and inflammation with
      resulting epigenetic changes at both the placental and fetal levels are important
      areas of continued investigation. 

PMID- 25617043
TI  - Combined inhalation and oral supplementation of Vitamin A and Vitamin D: a
      possible prevention and therapy for tuberculosis.
AB  - Tuberculosis is continuing as a problem of mankind. With evolution, MDR and XDR
      forms of tuberculosis have emerged from drug sensitive strain. MDR and XDR
      strains are resistant to most of the antibiotics, making the management more
      difficult. BCG vaccine is not providing complete protection against tuberculosis.
      Therefore new infections are spreading at a tremendous rate. At the present
      moment there is experimental evidence to believe that Vitamin A and Vitamin D has
      anti-mycobacterial property. It is in this context, we have hypothesized a host
      based approach using the above vitamins that can cause possible prevention and
      cure of tuberculosis with minimal chance of resistance or toxicity. 

PMID- 25617042
TI  - Obsessive-compulsive personality disorder: a current review.
AB  - This review provides a current overview on the diagnostics, epidemiology, co
      occurrences, aetiology and treatment of obsessive-compulsive personality disorder
      (OCPD). The diagnostic criteria for OCPD according to the recently published
      Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      5) include an official set of criteria for clinical practice and a new,
      alternative set of criteria for research purposes. OCPD is a personality disorder
      prevalent in the general population (3-8 %) that is more common in older and less
      educated individuals. Findings on sex distribution and course of OCPD are
      inconsistent. OCPD is comorbid with several other medical and psychological
      conditions. As for causes of OCPD, most empirical evidence provides support for
      disturbed attachment as well as the heritability of OCPD. So far, cognitive
      (behavioural) therapy is the best validated treatment of OCPD. Self-esteem
      variability, stronger early alliances as well as the distress level seem to
      predict cognitive (behavioural) therapy outcome. Future research is needed to
      further advance knowledge in OCPD and to resolve inconsistencies.

PMID- 25617044
TI  - Are CXCL13/CXCR5/FAK critical regulators of MSCs migration and differentiation?
AB  - Osteonecrosis of the femoral head is a common and challenging disease worldwide.
      The traditional treatments, such as core decompression procedure and joint
      replacement, are not satisfactory due to the limited outcome, repetitive surgery
      and cost. In recent years, autologous mesenchymal stem cells (MSCs) implantation
      into the femoral head has emerged as a promising method. The homing and
      differentiation of MSCs is determined by chemokines and their receptors, specific
      signals present in the micro-environment of the damaged tissue. CXCL13/CXCR5,
      highly expressed in the osteoblast and MSCs, are tissue specific and selectively
      migrate MSCs, thereafter triggering phosphorylation of focal adhesionkinase
      through mitogen-activated protein kinase pathway. Considering these
      characteristics, we hypothesize that CXCL13/CXCR5/FAK are critical signals in the
      trafficking and differentiation of MSCs. 

PMID- 25617046
TI  - Effects of Mediterranean diet supplemented with silybin-vitamin E-phospholipid
      complex in overweight patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease is the most common liver disease
      worldwide. AIM: The aim of this study is to compare the metabolic effects of the
      Mediterranean diet versus the diet associated with silybin, phosphatidylcholine
      and vitamin E complex in overweight patients with non-alcoholic fatty liver
      disease. METHODS: Thirty Caucasian overweight patients were randomized into three
      groups of 10 (Groups A, B and C). A personalized Mediterranean diet was started
      in Group A and B patients. In association with the diet, Group B patients were
      given Realsil complex, daily, for 6 months. Group C patients refused any
      treatment. RESULTS: We showed that the Mediterranean diet alone, or in
      association with the Realsil complex, led to the significant variation in BMI,
      waist circumference, total cholesterol and triglycerides. We also observed a
      statistically significant decrease in homeostasis model assessment technique in
      Group B patients.

PMID- 25617045
TI  - Crystal structure and functional characterization of photosystem II-associated
      carbonic anhydrase CAH3 in Chlamydomonas reinhardtii.
AB  - In oxygenic photosynthesis, light energy is stored in the form of chemical energy
      by converting CO2 and water into carbohydrates. The light-driven oxidation of
      water that provides the electrons and protons for the subsequent CO2 fixation
      takes place in photosystem II (PSII). Recent studies show that in higher plants,
      HCO3 (-) increases PSII activity by acting as a mobile acceptor of the protons
      produced by PSII. In the green alga Chlamydomonas reinhardtii, a luminal carbonic
      anhydrase, CrCAH3, was suggested to improve proton removal from PSII, possibly by
      rapid reformation of HCO3 (-) from CO2. In this study, we investigated the
      interplay between PSII and CrCAH3 by membrane inlet mass spectrometry and x-ray
      crystallography. Membrane inlet mass spectrometry measurements showed that CrCAH3
      was most active at the slightly acidic pH values prevalent in the thylakoid lumen
      under illumination. Two crystal structures of CrCAH3 in complex with either
      acetazolamide or phosphate ions were determined at 2.6- and 2.7-A resolution,
      respectively. CrCAH3 is a dimer at pH 4.1 that is stabilized by swapping of the N
      terminal arms, a feature not previously observed in alpha-type carbonic
      anhydrases. The structure contains a disulfide bond, and redox titration of
      CrCAH3 function with dithiothreitol suggested a possible redox regulation of the
      enzyme. The stimulating effect of CrCAH3 and CO2/HCO3 (-) on PSII activity was
      demonstrated by comparing the flash-induced oxygen evolution pattern of wild-type
      and CrCAH3-less PSII preparations. We showed that CrCAH3 has unique structural
      features that allow this enzyme to maximize PSII activity at low pH and CO2
      concentration.

PMID- 25617047
TI  - Alcohol and tobacco use in youth with and without chronic pain.
AB  - OBJECTIVE: To compare rates of alcohol and tobacco use in youth with and without
      chronic pain and to identify risk factors for use. METHODS: Participants included
      186 youth (95 mixed chronic pain; 91 without chronic pain; 12-18 years old) who
      reported current alcohol and tobacco use, pain intensity, activity limitations,
      loneliness, and depressive symptoms. RESULTS: Adolescents with chronic pain were
      less likely to use alcohol compared with adolescents without chronic pain (7.4%
      vs. 22%), and as likely to use tobacco (9% vs. 8%). Across groups, youth with
      higher depressive symptoms, less loneliness, and fewer activity limitations were
      more likely to endorse alcohol and tobacco use. Exploratory analyses revealed
      that risk factors for substance use differed among youth with and without chronic
      pain. CONCLUSIONS: Chronic pain may not increase risk for tobacco and alcohol use
      in adolescents. Research is needed to understand use of other substances in this
      medically vulnerable population.

PMID- 25617048
TI  - Validation of the Abdominal Pain Index using a revised scoring method.
AB  - OBJECTIVE: Evaluate the psychometric properties of child- and parent-report
      versions of the four-item Abdominal Pain Index (API) in children with functional
      abdominal pain (FAP) and healthy controls, using a revised scoring method that
      facilitates comparisons of scores across samples and time. METHODS: Pediatric
      patients aged 8-18 years with FAP and controls completed the API at baseline (N =
      1,967); a subset of their parents (N = 290) completed the API regarding the
      child's pain. Subsets of patients completed follow-up assessments at 2 weeks (N =
      231), 3 months (N = 330), and 6 months (N = 107). Subsets of both patients (N =
      389) and healthy controls (N = 172) completed a long-term follow-up assessment
      (mean age at follow-up = 20.21 years, SD = 3.75). RESULTS: The API demonstrated
      good concurrent, discriminant, and construct validity, as well as good internal
      consistency. CONCLUSION: We conclude that the API, using the revised scoring
      method, is a useful, reliable, and valid measure of abdominal pain severity.

PMID- 25617049
TI  - The role of PAPP-A in the IGF system: location, location, location.
AB  - Although discovered as a placental protein present abundantly in the circulation
      of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely
      expressed in multiple tissues. PAPP-A is a highly specific metalloproteinase
      binding tightly to glycosaminoglycans present on the surface of cells. By
      cleaving a subset of insulin-like growth factor binding proteins (IGFBPs), PAPP-A
      thus functions within tissues as a growth-promoting enzyme, releasing bioactive
      IGF in close proximity to the IGF receptor. IGFBP-4 is believed to be the
      principal PAPP-A substrate, and the focus in this review is on PAPP-A enzymatic
      activity and its role in the PAPP-A-IGFBP-4-IGF axis, which is subject to
      regulation at several different levels. These include e.g., transcriptional
      control, competing reactions potentially sequestering IGF from IGFBP-4 and hence
      antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP
      A. The latter may involve the protein stanniocalcin-2 (STC2), recently found to
      potently inhibit PAPP-A activity by forming a covalent complex with PAPP-A. PAPP
      A or complex-bound variants may escape from pathological tissues into the
      circulation. It is emphasized that the potential use of PAPP-A as a diagnostic or
      predictive biomarker in nonpregnant individuals requires precise knowledge of
      analyte identity and assay specificity in addition to an appropriate material for
      standardization. Finally, PAPP-A may serve as a therapeutic target to indirectly
      inhibit IGF signaling in tissues where this is driven by increased PAPP-A
      activity. By taking advantage of the intricate interaction between PAPP-A and
      IGFBP-4, highly specific and selective inhibition of PAPP-A is possible. 

PMID- 25617051
TI  - Involvement of the insulin-like growth factor binding proteins in the cancer cell
      response to DNA damage.
AB  - The complex mechanisms that cells have evolved to meet the challenge of constant
      exposure to DNA-damaging stimuli, also serve to protect cancer cells from the
      cytotoxic effects of chemo- and radiotherapy. IGFBPs appear to be involved,
      directly or indirectly, in some of these protective mechanisms. Activation of p53
      is an early response to genotoxic stress, and all six human IGFBP genes have
      predicted p53 response elements in their promoter and/or intronic regions, at
      least some of which are functional. IGFBP3 has been extensively characterized as
      a p53-inducible gene, but in some cases it is suppressed by mutant p53 forms. DNA
      double-strand breaks (DSBs), induced by radiotherapy and some chemotherapies,
      potentially lead to apoptotic cell death, senescence, or repair and recovery. DSB
      damage can be repaired by homologous recombination or non-homologous end-joining
      (NHEJ), depending on the cell cycle stage, availability of key repair proteins,
      and other factors. The epidermal growth factor receptor (EGFR) has been
      implicated in the NHEJ pathway, and EGFR inhibition may inhibit repair, promoting
      apoptosis and thus improving sensitivity to chemotherapy or radiotherapy. Both
      IGFBP-3 and IGFBP-6 interact with components of the NHEJ pathway, and IGFBP-3 can
      facilitate this process through direct interaction with both EGFR and the
      catalytic subunit of DNA-PK. Cell fate after DNA damage may in part be regulated
      by the balance between the sphingolipids ceramide and sphingosine-1-phosphate,
      and IGFBPs can influence the production of both lipids. A better understanding of
      the involvement of IGFBPs in the DNA damage response in cancer cells may lead to
      improved methods of sensitizing cancers to DNA-damaging therapies. 

PMID- 25617053
TI  - Chronic effects of 17alpha-ethinylestradiol, fluoxetine, and the mixture on
      individual and population-level end points in Daphnia magna.
AB  - Many pharmaceuticals and personal care products (PPCPs) enter the environment
      continuously. Because these chemicals are not intended for environmental
      applications, testing for environmental effects is not mandatory, and thus
      relatively little is known about their ecological effects, particularly on
      invertebrate species. To better understand the effects of PPCPs on freshwater
      invertebrates, we exposed the water flea Daphnia magna to environmentally
      relevant concentrations of the pharmaceuticals 17alpha-ethinylestradiol (EE2) and
      fluoxetine both individually and as a mixture for 40 days. Exposure to EE2
      decreased the number of neonates produced per female at 0.1 and 1.0 ug/L EE2,
      whereas fluoxetine increased mortality and neonate production at 100 ug/L.
      Exposure to the mixture of EE2 + fluoxetine increased time to first reproduction
      in medium and high mixture treatments and decreased time to death and neonate
      production in the high mixture treatment. When these individual parameters were
      integrated into a demographic model, population growth rate decreased when D.
      magna were exposed to 0.1 and 1.0 ug/L EE2, 100 ug/L fluoxetine, and low and high
      mixture treatments. When we compared the results of our extended 40 day exposures
      with data from only the first 21 days, the standard duration of chronic toxicity
      tests with D. magna, the effects of pharmaceutical exposure were generally
      significant at lower chemical concentrations during the 21-day period compared
      with the 40-day exposures, which points to the importance of exposure duration in
      drawing inferences from toxicity studies.

PMID- 25617050
TI  - IGFBP-2 - taking the lead in growth, metabolism and cancer.
AB  - The activity of the Insulin-like Growth Factors (IGFs) ligands elicited via their
      receptors and transduced by various intracellular signal pathways is modulated by
      the IGF Binding Proteins (IGFBPs). Among all the IGFBPs, IGFBP-2 has been
      implicated in the regulation of IGF activity in most tissue and organs. Besides
      binding to IGFs in the circulation these IGF-regulatory activities of IGFBP-2
      involve interactions with components of the extracellular matrix, cell surface
      proteoglycans and integrin receptors. In addition to these local peri-cellular
      activities, IGFBP-2 exerts other key functions within the nucleus, where IGFBP-2
      directly or indirectly promotes transcriptional activation of specific genes. All
      of these IGFBP-2 activities, intrinsic or dependent on IGFs, contribute to its
      functional roles in growth/development, metabolism and malignancy as evidenced by
      studies in IGFBP-2 animal models and also by many in vitro studies. Finally,
      preclinical studies have demonstrated that IGFBP-2 administration can be
      beneficial in improving metabolic responses (inhibition of adipogenesis and
      enhanced insulin sensitivity), while blockade of IGFBP-2 appears to be an
      effective approach to inhibiting tumour growth and metastasis. 

PMID- 25617054
TI  - Preparation of a manganese dioxide/carbon fiber electrode for electrosorptive
      removal of copper ions from water.
AB  - MnO2 is an effective adsorbent for many metal ions and a promising electrode
      material for electrochemical supercapacitors. In this paper, we successfully
      combined the two functions through preparing a MnO2/carbon fiber (CF) composite
      as an electrosorptive electrode. The thin MnO2 film was deposited onto CF by an
      anodic eletrodeposition method. The MnO2/CF electrodes had ideal pseudocapacitive
      behavior and high capacitive reversibility. The specific capacitance of the
      MnO2/CF electrode reached a maximum value of 387 F/g, which is quite competitive
      compared with literature values. At 0.8 V applied potential, the maximum Cu(2+)
      adsorption capacity of the MnO2/CF electrode was 172.88 mg/g, which is more than
      2 times higher than common MnO2 adsorbents without an electric field imposed. SEM
      images showed that MnO2 nanoflowers with several "petals" were uniformly
      distributed on the CF surface. Enhancement of adsorption by the polarization
      potential and the unique microstructure of the deposited MnO2 may be the source
      of the outstanding adsorption ability of the MnO2/CF electrode. The MnO2/CF
      electrode could be regenerated quickly by reversing the voltage. The deposition
      time of 1000 s was optimum for achieving maximum capacitance and Cu(2+) removal
      performance. The MnO2/CF composite electrosorptive electrode is a promising
      candidate for Cu(2+) removal from aqueous solution.

PMID- 25617052
TI  - Increased CCN2, substance P and tissue fibrosis are associated with sensorimotor
      declines in a rat model of repetitive overuse injury.
AB  - Key clinical features of cumulative trauma disorders include pain, muscle
      weakness, and tissue fibrosis, although the etiology is still under
      investigation. Here, we characterized the temporal pattern of altered
      sensorimotor behaviors and inflammatory and fibrogenic processes occurring in
      forearm muscles and serum of young adult, female rats performing an operant, high
      repetition high force (HRHF) reaching and grasping task for 6, 12, or 18 weeks.
      Palmar mechanical sensitivity, cold temperature avoidance and spontaneous
      behavioral changes increased, while grip strength declined, in 18-week HRHF rats,
      compared to controls. Flexor digitorum muscles had increased MCP-1 levels after
      training and increased TNFalpha in 6-week HRHF rats. Serum had increased IL
      1beta, IL-10 and IP-10 after training. Yet both muscle and serum inflammation
      resolved by week 18. In contrast, IFNgamma increased at week 18 in both muscle
      and serum. Given the anti-fibrotic role of IFNgamma, and to identify a mechanism
      for the continued grip strength losses and behavioral sensitivities, we evaluated
      the fibrogenic proteins CCN2, collagen type I and TGFB1, as well as the
      nociceptive/fibrogenic peptide substance P. Each increased in and around flexor
      digitorum muscles and extracellular matrix in the mid-forearm, and in nerves of
      the forepaw at 18 weeks. CCN2 was also increased in serum at week 18. At a time
      when inflammation had subsided, increases in fibrogenic proteins correlated with
      sensorimotor declines. Thus, muscle and nerve fibrosis may be critical components
      of chronic work-related musculoskeletal disorders. CCN2 and substance P may serve
      as potential targets for therapeutic intervention, and CCN2 as a serum biomarker
      of fibrosis progression. 

PMID- 25617055
TI  - Ageing influence in the evolution of strength and muscle mass in women with
      fibromyalgia: the al-Andalus project.
AB  - Fibromyalgia is associated with physical disabilities in daily activities.
      Moreover, patients with fibromyalgia present similar levels of functional
      capacity and physical condition than elderly people. The aim of this study was to
      analyse the evolution of strength and muscle mass in women with fibromyalgia
      along ageing. A total sample of 492 fibromyalgia patients and 279 healthy control
      women were included in the study. Participants in each group were further divided
      into four age subgroups: subgroup 1: 30-39 years old, subgroup 2: 40-49 years
      old, subgroup 3: 50-59 years old and subgroup 4: 60-69 years old. Standardized
      field-based fitness tests were used to assess muscle strength (30-s chair stand,
      handgrip strength and arm curl tests). Fibromyalgia patients did not show
      impairment on muscle mass along ageing, without values of skeletal muscle mass
      index below 6.76 kg/m(2) in any group. However, in all variables of muscle
      strength, the fibromyalgia group showed less strength than the healthy group (p <
      0.05) for all age groups. As expected, handgrip strength test showed differences
      along ageing only in the fibromyalgia group (p < 0.001). Age was inversely
      associated with skeletal muscle mass (r = -0.155, p < 0.01) and handgrip strength
      (r = -0.230, p < 0.001) in the FM group. Women with fibromyalgia showed a
      reduction in muscle strength along ageing process, with significantly lower
      scores than healthy women for each age group, representing a risk of dynapenia. 

PMID- 25617056
TI  - [Urinary schistosomiasis contracted in a child in Corsica].

PMID- 25617057
TI  - Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1beta-induced
      catabolic gene expression in cartilage.
AB  - BACKGROUND: In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and
      catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1beta)
      is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes
      and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF
      2alpha, encoded by Epas1) is the catabolic transcription factor in the
      osteoarthritic process. The purpose of this study is to validate the effects of
      ecdysteroids (Ecd) on IL-1beta-induced cartilage catabolism and the possible role
      of Ecd in treatment or prevention of early OA. METHODS: Chondrocytes and
      articular cartilage was harvested from newborn ICR mice. Ecd effect on
      chondrocytes viability was tested and the optimal concentration was determined by
      MTT assay. The effect of HIF-2alpha (EPAS1) in cartilage catabolism simulated by
      IL-1beta (5 ng/ml) was evaluated by articular cartilage explants culture. The
      effects of Ecd on IL-1beta-induced inflammatory conditions and their related
      catabolic genes expression were analyzed. RESULTS: Interleukin-1beta (IL-1beta)
      treatment on primary mouse articular cartilage explants enhanced their Epas1,
      matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down
      regulated collagen type II (Col2a1) gene expression. With the pre-treatment of
      10(-8) M Ecd, the catabolic effects of IL-1beta on articular cartilage were
      scavenged. CONCLUSION: In conclusions, Ecd can reduce the IL-1beta-induced
      inflammatory effect of the cartilage. Ecd may suppress IL-1beta-induced cartilage
      catabolism via HIF-2alpha pathway.

PMID- 25617058
TI  - [Measurement of d-dimers in non-valvular atrial fibrillation. First prospective
      Tunisian study].
AB  - Atrial fibrillation can expose to thrombo-embolic complications. Many biomarkers
      have been tested to refine the stratification of thrombo-embolic risk. The study
      aim was to assess the interest of the d-dimer testing in this pathology. We
      conducted a prospective observational study including 50 cases and 19 controls,
      enrolled at the cardiology department of the Mongi Slim Hospital, from July to
      November 2012. The d-dimer assay was performed on mini-VIDAS((r)) and analyzed
      according to clinical, echocardiographic and biological data. The mean age of
      patients was 61.8+/-10.6years. The mean CHA2DS2-VASc score was 2.58+/-1.31. The
      average of D-dimer levels was 590+/-506ng/ml in patients and 225.26+/-112.95ng/ml
      in controls (P=0.02). No significant difference has been found between the d
      dimer level and age, sex, type and etiology of atrial fibrillation, the CHA2DS2
      VASc score, the left atrial surface. Among patients on acenocoumarol, d-dimer
      levels was significantly higher in patients with an INR<2 compared to those with
      an INR>=2 (P=0.004). We identified a positive d-dimer threshold (300ng/ml) in
      patients distinguishing them significantly with controls (P<0.001). In
      conclusion, the measurement of d-dimers could help clinicians to identify
      patients with atrial fibrillation having an increased coagulability and,
      therefore, an increased thrombo-embolic risk. It could be complementary to the
      determination of INR in monitoring anticoagulation therapy: d-dimers level
      refines the thrombo-embolic risk and INR measurement assesses the level of
      anticoagulation and the bleeding risk. 

PMID- 25617060
TI  - Telehealth can meet the health care needs of aging rural veterans.

PMID- 25617059
TI  - Genetic engineering of Francisella tularensis LVS for use as a novel live vaccine
      platform against Pseudomonas aeruginosa infections.
AB  - Francisella tularensis LVS (Live Vaccine Strain) is an attenuated bacterium that
      has been used as a live vaccine. Patients immunized with this organism show a
      very long-term memory response (over 30 years post vaccination) evidenced by the
      presence of indicators of robust cell-mediated immunity. Because F. tularensis
      LVS is such a potent vaccine, we hypothesized that this organism would be an
      effective vaccine platform. First, we sought to determine if we could genetically
      modify this strain to produce protective antigens of a heterologous pathogen.
      Currently, there is not a licensed vaccine against the important opportunistic
      bacterial pathogen, Pseudomonas aeruginosa. Because many P. aeruginosa strains
      are also drug resistant, the need for effective vaccines is magnified. Here, F.
      tularensis LVS was genetically modified to express surface proteins PilAPa,
      OprFPa, and FliCPa of P. aeruginosa. Immunization of mice with LVS expressing the
      recombinant FliCPa led to a significant production of antibodies specific for P.
      aeruginosa. However, mice that had been immunized with LVS expressing PilAPa or
      OprFPa did not produce high levels of antibodies specific for P. aerugionsa.
      Therefore, the recombinant LVS strain engineered to produce FliCPa may be able to
      provide immune protection against a P. aeruginosa challenge. However for future
      use of this vaccine platform, selection of the appropriate recombinant antigen is
      critical as not all recombinant antigens expressed in this strain were
      immunogenic. 

PMID- 25617061
TI  - Measuring spatial-numerical associations: evidence for a purely conceptual link.
AB  - Previous work on spatial-numerical association (SNAs) included either spatially
      distributed stimuli or responses. This raises the possibility that the inferred
      spatial nature of number concepts was a methodological artifact. We present
      results from a novel task that involves two categories (spatially oriented
      objects and number magnitudes) and dissociates spatial classification from number
      classification. The results reveal SNAs without inferential limitations of
      previous work and point to a working memory mechanism that transfers spatial
      coding across categories. 

PMID- 25617062
TI  - Do chronic disease patients value generic health states differently from
      individuals with no chronic disease? A case of a multicultural Asian population.
AB  - BACKGROUND: There is conflicting evidence as to whether patients with chronic
      disease value hypothetical health states differently from individuals who have
      not experienced any long-lasting diseases. Furthermore, most studies regarding
      this issue have been conducted in western countries, with only one conducted in
      Asia. We aimed to evaluate possible systematic differences in the valuation of
      EuroQol Group five dimensions 3-level (EQ-5D-3L) health states by chronic disease
      patients and a population with no chronic disease in Singapore. METHODS: A face
      to-face survey for the valuation of the 42 health states of the EQ-5D-3L using
      the visual analogue scale (VAS) method was conducted in Singapore. The survey
      also asked participants to report any chronic diseases they had. Ordinary least
      square regression models were employed to assess possible differences in the
      valuation scores of all health states, severe health states and non-severe health
      states by individual chronic disease patient groups (diabetes, rheumatism,
      hypertension, heart diseases and lung diseases) and by a group of participants
      with no chronic disease. A difference of 4 to 8 points on the 100-point VAS was
      considered to be of practical significance. RESULTS: The analysis included 332
      participants with at least one chronic disease and 651 participants with no
      chronic disease. After taking health state descriptors and covariates into
      account, mean valuation scores of the 42 health states by the heart disease group
      were higher by 4.6 points (p-value = 0.032) compared to the no chronic disease
      group. Specifically, the heart disease group valued severe health states 5.4
      points higher (p-value = 0.025) than the no chronic disease group. There was no
      practically significant difference in the mean valuation score of non-severe
      health states between the heart disease group and the no chronic disease group.
      No practically significant differences were found in the mean valuation score of
      all health states, severe health states and non-severe health states between any
      other chronic disease group and the no chronic disease group. CONCLUSIONS: In
      Singapore, heart disease patients valued EQ-5D-3L severe health states
      differently from individuals with no chronic disease. Other chronic disease
      groups did not value EQ-5D-3L health states differently from the no chronic
      disease group.

PMID- 25617063
TI  - Fact-finding Survey in Response to the Manipulation of Personal Alarm Dosimeter
      Collection Efficiency: Lessons Learned About Post-Emergency Radiation Protection
      from the TEPCO Fukushima Daiichi APP Accident.
AB  - During emergency work at TEPCO Fukushima Daiichi Atomic Power Plant on December
      1, 2011 a subcontractor demanded that its contracted workers cover their personal
      alarm dosimeters (PAD) with 3-cm-thick lead plates to lower dosimeter readings.
      As a response, the Ministry of Health, Labour and Welfare (MHLW) conducted a fact
      finding survey to identify similar cases and devise measures to prevent a
      recurrence of this incident. To screen the suspected cases, the MHLW extracted:
      a) cases in which a PAD reading was at least 15% higher than the reading obtained
      from a radio-photolumine-scence dosimeter (RPD), where the dose was greater than
      5 mSv in a month (1813 data points), and b) dose data in which PAD readings were
      less than 50% of the expected dose, where exposure dose may exceed 1 mSv in a day
      (56 workers, 17,148 data points). From these screenings, the MHLW identified 50
      instances from TEPCO and nine primary contractors, including four general
      contractors, two plant manufacturers, and three plant maintenance companies as
      the subjects of the due diligence study of exposure data, including interviews.
      The results of the survey provide lessons that can also be applied to transition
      from emergency radiation protection to normal operation, as the application of
      emergency dose limits had ceased on December 16, 2011, in the affected plant.
      Based on the results of the survey, the MHLW provided administrative guidance
      documents to TEPCO and 37 primary contractors. The major points of these
      documents include: a) identification of recorded dose values by comparison of PAD
      readings to RPD readings, b) storage and management of RPDs and control badges,
      c) circulation management of PADs and access control to the affected plant, d)
      estimation of planned doses and setting of alarm values of PADs, e) actions to be
      taken by contractors if worker dose limits are reached, and f) physical measures
      to prevent recurrence of the incident. 

PMID- 25617065
TI  - Retraction note to: Preliminary comparing the toxicities of the hybrid cry1Acs
      fused with different heterogenous genes provided guidance for the fusion
      expression of Cry proteins. World J Microbiol Biotechnol (2012 Jan; 28(1):397
      400).

PMID- 25617064
TI  - Apoptosis and expression of argyrophilic nucleolus organizer regions in
      epithelial neoplasms of the larynx.
AB  - INTRODUCTION: Occurrence of apoptosis and expression of proliferative markers are
      powerful tools to establish a prognosis in the follow-up of cancer. OBJECTIVE: To
      evaluate the growth fraction in papillomas and laryngeal squamous cell carcinomas
      with three degrees of differentiation through apoptosis and the expression of
      nucleolus organizer regions. METHODS: Retrospective study from which paraffin
      material was submitted to microtomy and hematoxylin-eosin and silver staining.
      Stained slides were used to quantify the apoptotic index and the number of
      nucleolus organizer regions by morphometry. RESULTS: Apoptosis was significantly
      more frequent in well differentiated carcinomas and in papillomas, and a higher
      growth fraction of expressed nucleolus organizer regions and cells that expressed
      a greater than average number of nucleolus organizer regions were more frequently
      noted in undifferentiated carcinomas. CONCLUSIONS: Thus, it was possible to
      verify that a high apoptotic index was associated with a lower chance of tumor
      differentiation in carcinomas, while a greater number of total nucleolus
      organizer regions, cells expressing nucleolus organizer regions above average and
      a higher growth fraction were associated with greater likelihood of abnormal cell
      proliferation and increased tumor differentiation.

PMID- 25617066
TI  - mRNA secondary structure engineering of Thermobifida fusca endoglucanase (Cel6A)
      for enhanced expression in Escherichia coli.
AB  - The sequence and structure of mRNA plays an important role in solubility and
      expression of the translated protein. To divulge the role of mRNA secondary
      structure and its thermodynamics in the expression level of the recombinant
      endoglucanase in Escherichia coli, 5'-end of the mRNA was thermodynamically
      optimized. Molecular engineering was done by introducing two silent synonymous
      mutations at positions +5 (UCU with UCC) and +7 (UUC with UUU) of the 5'-end of
      mRNA to relieve hybridization with ribosomal binding site. Two variants of
      glycoside hydrolase family six endoglucanase, wild type (cel6A.wt) and mutant
      (cel6A.mut) from Thermobifida fusca were expressed and characterized in E. coli
      using T7 promoter-based expression vector; pET22b(+). Enhanced expression level
      of engineered construct (Cel6A.mut) with ?G = -2.7 kcal mol(-1)was observed. It
      showed up to ~45 % higher expression as compared to the wild type construct
      (Cel6A.wt) having ?G = -7.8 kcal mol(-1) and ~25 % expression to the total cell
      proteins. Heterologous protein was purified by heating the recombinant E. coli
      BL21 (DE3) CodonPlus at 60  degrees C. The optimum pH for enzyme activity was six
      and optimum temperature was 60  degrees C. Maximum activity was observed 4.5 Umg(
      1) on CMC. Hydrolytic activity was also observed on insoluble substrates, i.e.
      RAC (2.8 Umg(-1)), alkali treated bagass (1.7 Umg(-1)), filter paper (1.2 Umg(
      1)) and BMCC (0.3 Umg(-1)). Metal ions affect endoglucanase activity in different
      ways. Only Fe(2+) exhibited 20.8 % stimulatory effects on enzyme activity. Enzyme
      activity was profoundly inhibited by Hg2(+) (91.8 %).

PMID- 25617067
TI  - [Publishing in Spanish: an opportunity and a challenge].

PMID- 25617068
TI  - Expectoration of the staple line: a delayed complication after previous
      lobectomy.
AB  - In the literature, bronchopleural fistula after thoracic surgery is usually
      reported in the perioperative setting; however, the incidence of delayed fistula
      still remains unknown. We herein report a case of a 54-year old man who was
      referred to the Emergency Department for dyspnoea and productive cough with
      expectoration of a whitish 'suture-like' tissue. Two months before, the patient
      underwent an uneventful right lower lobectomy for squamous-cell lung cancer. A
      computed tomography scan revealed a para-mediastinal localized pneumothorax
      (measuring 6 cm in the major axis) starting from a right lower bronchus
      interruption associated with a middle lobe consolidation. The patient was
      consequently admitted for respiratory monitoring and underwent a fibre-optic
      bronchoscopy to assess bronchial integrity: the right lower bronchus was
      completely dehiscent and connected to an empty pleural closed pouch, with no
      inflammatory signs or sputum-like effusion. After the procedure, the clinical
      course was unremarkable with gradual improvement of clinical conditions: in
      particular, the cough disappeared and no sign of fever, leucocytosis or
      respiratory failure was observed. Thus, after a multidisciplinary meeting, the
      patient was discharged 7 days after admission and re-evaluated monthly. Six
      months after diagnosis, the patient was symptom-free with complete closure of the
      fistula on radiological imaging. 

PMID- 25617069
TI  - Health-related physical fitness assessment in a community-based cancer
      rehabilitation setting.
AB  - PURPOSE: Assessment of physical fitness is important in order to set goals,
      appropriately prescribe exercise, and monitor change over time. This study aimed
      to determine the utility of a standardized physical fitness assessment for use in
      cancer-specific, community-based exercise programs. METHODS: Tests anticipated to
      be feasible and suitable for a community setting and a wide range of ages and
      physical function were chosen to measure body composition, aerobic fitness,
      strength, flexibility, and balance. Cancer Exercise Trainers/Specialists at
      cancer-specific, community-based exercise programs assessed new clients (n = 60)
      at enrollment, designed individualized exercise programs, and then performed a re
      assessment 3-6 months later (n = 34). RESULTS: Resting heart rate, blood
      pressure, body mass index, waist circumference, handgrip strength, chair stands,
      sit-and-reach, back scratch, single-leg standing, and timed up-and-go tests were
      considered suitable and feasible tests/measures, as they were performed in most
      (>=88 %) participants. The ability to capture change was also noted for resting
      blood pressure (-7/-5 mmHg, p = 0.02), chair stands (+4, p < 0.01), handgrip
      strength (+2 kg, p < 0.01), and sit-and-reach (+3 cm, p = 0.03). While the
      submaximal treadmill test captured a meaningful improvement in aerobic fitness
      (+62 s, p = 0.17), it was not completed in 33 % of participants. Change in
      mobility, using the timed up-and-go was nominal and was not performed in 27 %.
      CONCLUSION: Submaximal treadmill testing, handgrip dynamometry, chair stands, and
      sit-and-reach tests were feasible, suitable, and provided meaningful physical
      fitness information in a cancer-specific, community-based, exercise program
      setting. However, a shorter treadmill protocol and more sensitive balance and
      upper body flexibility tests should be investigated.

PMID- 25617070
TI  - The frequency of missed delirium in patients referred to palliative care in a
      comprehensive cancer center.
AB  - BACKGROUND: Delirium is one of the most common neuropsychiatric complications in
      advanced cancer patients with a frequency of up to 85 % before death. It is
      associated with adverse clinical outcomes such as increased morbidity and
      mortality as well as significant family and patient distress. The aim of our
      study is to determine at the frequency of missed delirium (MD) and identify
      factors associated with MD. METHODS: Seven hundred seventy-one consecutive
      palliative care inpatient consults from August 1, 2009 to January 31, 2010 were
      reviewed. Demographics, Memorial Delirium Assessment Scale (MDAS), Edmonton
      Symptom Assessment Scale (ESAS), primary referral symptom, Eastern Cooperative
      Oncology Group (ECOG), and physician diagnosis of delirium were collected along
      with delirium etiology, subtype, and reversibility. Delirium was diagnosed with a
      MDAS score of >= 7 or by a palliative medicine specialist using Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV TR)
      Criteria. MD was reported in those patients found to have delirium by the
      palliative medicine specialists but were referred by the primary team for other
      reasons besides delirium. Chi-squared test and Wilcoxon-Mann-Whitney test were
      used to examine the difference on measurements among or between different groups.
      Univariate logistic regression model was applied to assess for associations for
      MD. RESULTS: Two hundred fifty-two (33 %) had a diagnosis of delirium by the
      palliative medicine specialist. One hundred fifty-three (61 %) were missed by the
      primary referring team. Females comprised 53 % (n = 81), white 62 % (n = 95), and
      pain was the most common referral symptom (n = 77, 50 %). Hypoactive delirium was
      the most common subtype of delirium in MD (n = 47, 63 %). Opioid-related delirium
      was the most common etiology of MD (n = 47, 31 %). Patients referred for pain
      were more likely to have MD (odds ratio (OR) = 2.57, p = 0.0109). Of the 82
      patients with delirium that was reversed, 67 % (n = 55) had a diagnosis of MD.
      CONCLUSION: Sixty-one percent of patients with a diagnosis of delirium by a
      palliative care specialist were missed by the primary referring team. Patients
      with MD were frequently referred for pain. Universal screening of cancer patients
      for delirium is recommended.

PMID- 25617071
TI  - Impact of marital coping on the relationship between body image and sexuality
      among breast cancer survivors.
AB  - PURPOSE: The aims of the study were (1) to understand the relationship between
      women's marital coping efforts and body image as well as sexual relationships and
      (2) to test a hypothesized model suggesting that marital coping efforts have a
      mediating effect on the relationship between body image and sexual relationships
      among breast cancer survivors. METHODS: A total of 135 breast cancer survivors
      who had finished cancer treatment completed a self-reported questionnaire
      concerning body image, marital coping efforts, and sexual relationship. RESULTS:
      Body image, marital coping, and sexual relationship were found to be
      significantly correlated with each other. The final path model showed that
      negative marital coping efforts, including avoidance and self-blame,
      significantly mediated the effect of women's body image on their sexual
      relationships. Although a positive approach did not correlate with body image, it
      did significantly correlate with women's sexual relationships. CONCLUSIONS: Our
      study demonstrated that negative marital coping using self-blame and avoidance
      mediated the association between body image and sexual relationship. Future
      interventions to address the body image and sexual life of breast cancer
      survivors should be considered using positive approaches that prevent disengaged
      avoidance or self-blame coping efforts intended to deal with marital stress.

PMID- 25617072
TI  - Integration of complementary medicine in supportive cancer care: survey of health
      care providers' perspectives from 16 countries in the Middle East.
AB  - INTRODUCTION: In this multinational Middle-Eastern study, we assessed health-care
      providers' (HCPs) perspectives on their patients' use of complementary and
      traditional medicine (CTM) and identified the leading barriers to CTM integration
      in supportive cancer care. METHODS: A 17-item questionnaire was developed and
      administered to HCPs attending palliative medicine workshops conducted across the
      Middle East by the Middle East Cancer Consortium. RESULTS: 339 HCPs from 16
      countries across the Middle East completed the questionnaire (80.3 % response
      rate). Respondents perceived their patients' reasons for CTM use primarily in the
      context of cancer cure (63 %) and quality of life (QOL) improvement (57 %).
      Expectation regarding CTM's role in cancer cure/survival was more pronounced in
      Turkey, Jordan, the Palestinian Authority, and the Persian Gulf area. In
      contrast, the expectation that CTM would improve QOL was more emphasized in
      Israel. A mid-position between the cure/survival and QOL poles was observed in
      Cyprus, Lebanon, and the North African countries. Leading barriers to CTM
      integration in supportive cancer care included oncologists' skepticism and a gap
      between patients' expectations and HCP's objectives. Respondents' leading
      recommendation to HCPs was to communicate integrative care emphasizing well-being
      and improved functioning in accordance with their patients' health beliefs.
      CONCLUSION: CTM integration in supportive cancer care can be facilitated by
      implementing a platform for Middle Eastern clinical collaborations. HCPs'
      expectations and experiences with CTM have been positive in the oncology setting.
      These data need to be corroborated with information of patients' expectations on
      the provision of CTM over all phases of the oncology treatment.

PMID- 25617073
TI  - Comparison of antibiotic prophylaxis with cotrimoxazole/colistin (COT/COL) versus
      ciprofloxacin (CIP) in patients with acute myeloid leukemia.
AB  - PURPOSE: Recent meta-analyses showed that antibiotic prophylaxis in patients with
      neutropenia after chemotherapy reduced the incidence of fever and mortality rate.
      Fluoroquinolones appear to be most effective and well tolerated. Thus, in April
      2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin
      (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute
      myeloid leukemia (AML). The aim of this retrospective study was to compare
      efficacy and development of bacterial resistance with two different prophylaxis
      regimens over a time period of more than 4 years. METHODS: Induction chemotherapy
      courses given for AML during the antibiotic prophylaxis period with COT/COL
      (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a
      standard questionnaire. RESULTS: Eighty-five courses in the COT/COL group and 105
      in the CIP group were analyzed. The incidence of fever was not significantly
      different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of
      microbiologically documented infections was nearly the same (29 vs 26 %; p =
      0.625). In addition, there was no significant difference in the incidence of
      clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of
      detected gram-positive and gram-negative bacteria. Of note, there was no increase
      in resistance rates or cases with Clostridium difficile-associated diarrhea in
      the CIP group. CONCLUSION: The antibiotic prophylaxis with CIP compared to
      COT/COL in AML was similarly effective with no increase in bacterial resistance.
      COT/COL may have the advantages of providing additional prophylaxis against
      Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional
      option for treatment of febrile neutropenia.

PMID- 25617074
TI  - [Erosive complications of mid urethral slings (MUS): 10 years of surgical
      experience].
AB  - OBJECTIVE: Evaluation of the diagnostic and therapeutic management of erosive
      complications after mid urethral sling (MUS) procedure: vaginal erosions (VE),
      bladder (BE) and urethral (UE). METHODS: Retrospective monocentric study
      concerning cohort of patients undergoing surgery from January 2002 to January
      2013 supported for erosive complications of MSU: TVT (Tension-free Vaginal Tape)
      or TOT (Trans-Obturateur Tape). RESULTS: Sixteen patients were diagnosed for
      erosive complications: 7 VE, 6 BE and 3 UE. Dyspareunia and vaginal discharge
      were observed in 86% patients (n=6/7) with VE. Conservative treatment by vaginal
      approach was systematically performed in cases of vaginal erosion. After removal
      of material, 100% dyspareunia were corrected. Postoperative continence was
      maintained in 57% of patients (n=4/7). Urinary infection was the main symptom of
      patients with BE. Severe dysuria was present in 66% of patients with a UE
      (n=2/3). First-line therapy by endoscopic treatment was performed in 77% of
      patients (n=7/9) with a BE or UE. A second surgery was required in 42% of
      patients treated with endoscopic first-line therapy (n=3/7) because of a new
      exposure of MUS. Three of nine patients recurred their incontinence after first
      line therapy (33%). CONCLUSION: The removal of device exposed vaginally in case
      VE systematically corrected symptoms with about 60% of continence. In case of BE
      or UE, endoscopic treatment in first-line therapy was rarely definitive (42%) and
      recurrence of incontinence appeared in 30% cases.

PMID- 25617075
TI  - Vascular Endothelial Growth Factor A c.*237C>T polymorphism is associated with
      bevacizumab efficacy and related hypertension in metastatic colorectal cancer.
AB  - BACKGROUND: No predictive marker has been yet identified for bevacizumab which is
      widely used in metastatic colorectal cancer. AIMS: Evaluate impact of single
      nucleotide polymorphisms involved in Vascular Endothelial Growth Factor pathway
      on efficacy and tolerance of bevacizumab. METHODS: We retrospectively included
      patients who were treated with bevacizumab-based chemotherapy for metastatic
      colorectal cancer, and for whom a deoxyribonucleic acid sample was available. Ten
      polymorphisms in Vascular Endothelial Growth Factor-A, his receptors and hypoxia
      inducible factor-1alpha were genotyped on germ line DNA using real-time
      polymerase chain reaction TaqMan((r)). RESULTS: 89 patients were included. The CC
      genotype for rs3025039 (Vascular Endothelial Growth Factor-A c.*237C>T) was
      associated with a significantly better time to treatment failure (14.2 months) as
      compared to the CT and TT genotypes (6.0 months) in univariate (p = 0.004) and
      multivariate (p = 0.022; HR = 0.57; 95% CI [0.35-0.92]) analysis. Patients with
      at least one T allele showed worse overall survival and progression-free survival
      as compared to homozygous CC patients in univariate analysis (respectively p =
      0.016 and p = 0.044). There was significantly more severe hypertension for the CC
      genotype (29.5%) compared to CT and TT genotypes (7.1%) (p = 0.022) in
      multivariate analysis. CONCLUSIONS: In this retrospective study, the rs3025039
      polymorphism was significantly associated with time to treatment failure and
      hypertension in patients treated with bevacizumab-based chemotherapy.

PMID- 25617076
TI  - The role of diffusion tensor tractography in the surgical treatment of pediatric
      optic chiasmatic gliomas.
AB  - Diffusion tensor tractography(DTT) can theoretically be used in assessing the
      optic chiasmatic glioma(OCGs),which are still in debate about optimal treatment.
      The purpose of this study was to investigate the role of this technology in
      offering more information about the tumor, assisting the debulking surgery, and
      helping to anticipate visual outcomes. As a prospective cohort study, the
      enrolled patients received routine pre- and postoperative neuro-ophthalmology,
      neuroimaging, and endocrine examinations. Fiber tractography was meanwhile
      performed based on diffusion tensor imaging examination. Identification of the
      position relationship between the lesions and residual optic path, and morphology
      analysis of them was done based on their DTT features. All the information was
      used for confirmation by the intraoperative findings. 11 pediatric patients were
      enrolled in this study. Most of them got subtotal resection of the tumors and
      stable postoperative visual outcomes. On the DTT imagings, the tumors were
      divided into infiltrative endophytic ones (TypeI) and inflated ones (TypeII),
      which can be subclassified as inferior and superior chiasmatic ones based on the
      positional relationships between the optic chiasm fibers and the tumors. These
      positional relationships were confirmed intraoperatively. The postoperative DTT
      images were quite different from preoperative ones. The application of DTT to
      children with OCGs is feasible, and valuable for getting more information about
      the disease, improving surgical techniques, and helping predict the overall and
      visual prognosis of the patients. The exact correlations of DTT features and
      visual outcomes need to be further verified.

PMID- 25617077
TI  - Is laparoscopic colorectal surgery beneficial for elderly patients? A systematic
      review and meta-analysis.
AB  - BACKGROUND: Elderly patients who undergo major abdominal surgery are potentially
      at a higher risk of perioperative mortality and postoperative complications.
      Although laparoscopic surgery has been widely accepted as a less invasive
      surgical procedure for colorectal diseases, the benefits for elderly patients
      have not been validated. AIM: To compare postoperative outcomes and long-term
      survival between laparoscopic and open colorectal surgery in the elderly
      population. METHODS: A literature search was electronically performed to identify
      all studies comparing postoperative outcomes between laparoscopic and open
      colorectal resections in the elderly population. Primary outcomes were
      postoperative mortality and complications, and the secondary outcome was long
      term survival. RESULTS: Overall, 30 studies (70,946 patients) met our inclusion
      criteria. Laparoscopic surgery was significantly associated with a decreased risk
      of perioperative mortality [odds ratio (OR), 0.55; 95% confidence interval (CI),
      0.45-0.68; P < 0.01] and postoperative complications (OR, 0.55; 95% CI, 0.48
      0.63; P < 0.01) compared with open surgery. There was no significant difference
      in long-term survival between the two procedures (OR, 0.89; 95% CI, 0.72-1.07; P
      = 0.31). CONCLUSIONS: Laparoscopic colorectal surgery in the elderly population
      has significant advantages in terms of short-term outcomes. Aggressive
      application of laparoscopic colorectal surgery should be considered for the
      elderly population.

PMID- 25617078
TI  - Strictureplasty for Treatment of Crohn's Disease: an ACS-NSQIP Database Analysis.
AB  - INTRODUCTION: Strictureplasty is an alternative to resection for treatment of
      Crohn's disease (CD) strictures. It preserves bowel length, and specialized
      centers report favorable outcomes. Strictureplasty rates, however, are thought to
      be low, and it was recently removed from required cases for colon and rectal
      surgery residents. We examined operative characteristics, and trends in its use
      using a large national database. MATERIALS AND METHODS: We examined the American
      College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)
      database from 2005 to 2012, identifying patients with CD who underwent
      strictureplasty. We identified patient characteristics, outcome variables, and
      trends in utilization of strictureplasty. RESULTS: A total of 9172 patients
      underwent surgery for CD. Two hundred fifty-six (2.8 %) underwent
      strictureplasty. Median preoperative albumin was 3.6. Preoperative steroid use
      and weight loss rates were 39 and 8 %. Rates of wound infection and organ space
      infection were 11 and 4 %. Rate of reoperation was 6 %. Outcomes did not change
      significantly over time (all p = NS). The proportion of CD operations that
      included a strictureplasty decreased from 5.1 to 1.7 % (OR 0.902 with each
      additional year, 95 % CI (0.852, 0.960), p < 0.001). CONCLUSION: Strictureplasty
      as treatment for CD is decreasing in the ACS-NSQIP database. Infectious
      complications and reoperation rates following strictureplasty are low and have
      not changed over time.

PMID- 25617079
TI  - Intraductal papillary mucinous neoplasm of the liver: GI image.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) are rare, mucin-producing,
      predominantly noninvasive tumors arising from epithelial cells. Most IPMNs arise
      from the pancreas. There exists a subset of IPMN of the biliary tract (BT-IPMN).
      IPMNs regardless of origin produce large amounts of mucin relative to scant
      amounts of epithelial cells, leading to mass effect disturbances in bile flow.
      Affected bile ducts exhibit marked dilatation. The majority of IPMN patients
      present with a non-malignant neoplasm. Because of potential for transformation,
      surgery is the treatment of choice. Bronchobiliary fistulas can present as
      congenital defects, following thoracoabodominal trauma, or as rare complications
      of diseases of the biliary tract such as BT-IPMN. There are no reported cases in
      the literature of bronchobiliary fistula associated with BT-IPMN, but there is a
      clear theoretical risk. 

PMID- 25617080
TI  - Image quality and radiation dose of single heartbeat 640-slice coronary CT
      angiography: a comparison between patients with chronic atrial fibrillation and
      subjects in normal sinus rhythm by propensity analysis.
AB  - OBJECTIVES: To evaluate image quality and radiation dose of single heartbeat 640
      slice coronary CT angiography (CCTA) in patients with chronic Atrial Fibrillation
      (cAF) in comparison with subjects in normal sinus rhythm. METHODS: A cohort of 71
      patients with cAF was matched with 71 subjects in normal sinus rhythm (NSR) and
      HR<=65 bpm using a matched by propensity analysis. All subjects underwent a
      single heartbeat CCTA with prospective gating. In subjects with cAF, we manually
      established the acquisition of data only from a single heartbeat. Mean effective
      dose and image quality, with both objective and subjective measures, were
      assessed. RESULTS: 96.4% of all segments in the cAF group had diagnostic image
      quality. The rate of subjects with at least one non-diagnostic segment was 14%
      and 2.8% (p=0.031) in the cAF and NRS groups, respectively. In the cAF group, the
      percentage of patients with at least one non-diagnostic segment for acquisition
      HR<=72 was 1.8% (1/55), and it did not significantly differ from the NSR group
      (2.8%; 2/71) (p=1.0). Objective quality parameters did not show a statistically
      significant difference between the two groups. The mean effective dose was 4.24+/
      1.24 mSv in the cAF group and 2.67+/-0.5 mSv in the sinus rhythm group (p<0.0001)
      with an increase by 59% in the cAF group with respect to the SNR group.
      CONCLUSIONS: A single heartbeat acquisition protocol with a 640-slice
      prospectively ECG-triggered CT angiography may be feasible in patients with cAF
      and HR below 72 bpm at the CT acquisition, although mean effective dose of this
      protocol in cAF group was 59% higher than in sinus rhythm one. In patients with
      cAF and a heart rate higher than 72 bpm, CCTA tends to have more movement
      associated artefacts.

PMID- 25617081
TI  - The need for predictability in coordination of ventilator treatment of newborn
      infants--a qualitative study.
AB  - OBJECTIVE: New strategies for interprofessional collaboration are needed to
      achieve best practice in the care of ventilated newborns. This study explores
      what physicians and nurses believe to be important to improve collaboration
      during ventilator treatment. METHODS: Qualitative data collected from one focus
      group were analysed using Gittell's theory of relational coordination. RESULTS:
      To optimise communication about and coordination of ventilator treatment, six
      strategies were needed: (1) a pathway toward the goal for each newborn, (2)
      regular meetings, (3) accurate communication following an established pattern in
      the rounds conference, (4) collaboration to improve interprofessional level of
      knowledge, (5) courage to communicate one's own point of view, and (6) flexible
      responsibility in extubation situations. CONCLUSION: By identifying weak areas in
      collaboration, nurses and physicians were inspired to suggest and discuss
      concrete improvements of work practices in the neonatal intensive care unit.
      Nurses and physicians can coordinate ventilator treatment by using a pathway and
      at the same time enhance nurses' involvement and responsibility in order to
      increase the flexibility of job boundaries, allowing the professions to cover for
      each other's work.

PMID- 25617082
TI  - [Blood transfusion and paradoxes].

PMID- 25617083
TI  - Atypical hepatic abscess: Hepatic foreign body.

PMID- 25617084
TI  - Atypical cardiac tamponade in an octogenarian female.

PMID- 25617085
TI  - Syndrome of transient headache and neurologic deficits with cerebrospinal fluid
      lymphocytosis (HaNDL).

PMID- 25617086
TI  - Neonatal outcomes after the implantation of human embryos vitrified using a
      closed-system device.
AB  - PURPOSE: Closed vitrification poses a risk of adversely affecting embryo
      development, while it may minimize the risk of contamination. We assessed the
      effects of closed-system human embryo vitrification on fetal development after
      implantation, neonatal outcome, and clinical safety. METHODS: This was a
      retrospective cohort study conducted at a private fertility clinic. A total of
      875 vitrified-warmed blastocysts that were single-transferred under hormone
      replacement cycles between November 2011 and December 2013 were randomly divided
      into two groups (closed vitrification, n 313; open vitrification, n 562) after
      receiving the patients' consent forms. Developmental competence after
      implantation, including gestational age, birth weight, sex, Apgar score, and
      anomalies of newborns, after the transfer of blastocysts vitrified by closing
      vitrification was compared with that obtained in the case of open vitrification.
      RESULTS: There were no significant differences between the use of closed and open
      vitrification systems in embryo development after implantation, gestational age,
      birth weight, sex ratio, Apgar score, and congenital anomalies of newborns.
      CONCLUSION: Human embryos can be vitrified using a closed vitrification system
      without impairment of neonatal development.

PMID- 25617088
TI  - Systematic review of the effectiveness of strategies to encourage patients to
      remind healthcare professionals about their hand hygiene.
AB  - BACKGROUND: Patients could help to improve the hand hygiene (HH) compliance of
      healthcare professionals (HCPs) by reminding them to sanitize their hands. AIM:
      To review the effectiveness of strategies aimed at increasing patient involvement
      in reminding HCPs about their HH. METHODS: A systematic review was conducted
      across Medline, EMBASE and PsycINFO between 1980 and 2013. FINDINGS: Twenty-eight
      out of a possible 1956 articles were included. Of these, 23 articles evaluated
      the effectiveness of developed patient-focused strategies and five articles
      examined patients' attitudes towards hypothetical strategies. Sixteen articles
      evaluated single-component strategies (e.g. videos) and 12 articles evaluated
      multi-modal approaches (e.g. combination of video and leaflet). Overall, the
      strategies showed promise in helping to increase patients' intentions and/or
      involvement in reminding HCPs about their HH. HCP encouragement appeared to be
      the most effective strategy. However, the methodological quality of the articles
      in relation to addressing the specific aims of this review was generally weak.
      CONCLUSION: A number of strategies are available to encourage patients to
      question HCPs about their HH. Better controlled studies with more robust outcome
      measures will enhance understanding about which strategies may be most successful
      and why.

PMID- 25617087
TI  - Morphokinetic parameters of early embryo development via time lapse monitoring
      and their effect on embryo selection and ICSI outcomes: a prospective cohort
      study.
AB  - PURPOSE: To compare the outcomes of embryos selected via time lapse monitoring
      (TLM) versus those selected with conventional methods of selection in subfertile
      women undergoing ICSI. METHODS: The study population (239 women) was classified
      into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2
      (conventional monitoring). Groups were compared according to the clinical and
      ICSI cycle characteristics and reproductive outcomes, while transfers were
      performed at day 2 or 3. Subgroup analyses were performed, in women of both
      groups according to age and clinical parameters, and in embryos of Group 1 based
      on their cellular events. RESULTS: There was a statistically significant
      difference between the two study groups with regard to the outcome parameters,
      favoring Group 1 and especially in women >40 years of age. No differences were
      found in subgroup analyses in participants of both groups, regarding the
      stimulation protocol used, number of the oocytes retrieved and type of
      subfertility, while in Group 1 the percentages of "in range" cellular events were
      higher in certain divisions in ages 35-40, non-smokers, and the GnRH-agonist
      group, and in embryos that resulted in pregnancy. CONCLUSION: Morphokinetic
      parameters of early embryo development via TLM are related to the characteristics
      of subfertile patients and associated with ICSI outcomes.

PMID- 25617089
TI  - Mandatory public reporting of healthcare-associated infections in developed
      countries: how can developing countries follow?
AB  - The threat posed by increased transmission of drug-resistant pathogens within
      healthcare settings and from healthcare settings to the community is very real
      and alarming. Although the developed world has taken strong steps to curb this
      menace, there has been little pressure on developing countries to take any
      corrective action. If the reporting of alarming rates of healthcare-associated
      infections (HCAIs) from hospitals in India and many other developing countries
      was made mandatory, it would help to force stakeholders (e.g. healthcare workers,
      legislators, administrators and policy makers in hospitals) to acknowledge and
      tackle the problem. This would introduce quality control in a long neglected area
      of health care, and enable patient empowerment which is practically non-existent
      in India. Healthcare institutions should commit towards enforcing 'zero
      tolerance' towards lapses in prevention of HCAIs. Public pressure would force the
      Indian Government to acknowledge the problem, and to allocate more funds to
      improve resources and infrastructure; this could substantially elevate the
      standard of health care given to the average Indian. Despite the numerous
      challenges, overall public benchmarking of HCAIs is a commendable goal that would
      go a long way towards tackling this menace in developing countries such as India.

PMID- 25617090
TI  - Safe central venous catheter insertion practice must extend beyond simply
      measuring catheter-associated bloodstream infections.

PMID- 25617091
TI  - Oxidative stress in neurological disease: is it the cause, consequence, or
      trigger of a chronic progressive form?

PMID- 25617092
TI  - Integrating nTMS Data into a Radiology Picture Archiving System.
AB  - Navigated transcranial magnetic stimulation (nTMS) is employed in eloquent brain
      area localization prior to intraoperative direct cortical electrical stimulations
      and neurosurgery. No commercial archiving or file transfer protocol existed for
      these studies. The aim of our project was to establish a standardized protocol
      for the transfer of nTMS results and medical assessments to the end users in
      pursuance of improving data security and facilitating presurgical planning. The
      existing infrastructure of the hospital's Radiology Department was used. Hospital
      information systems and networks were configured to allow communications and
      archiving of the study results, and in-house software was written for file
      manipulations and transfers. Graphical user interface with description
      suggestions and user-defined text legends enabled an easy and straightforward
      workflow for annotations and archiving of the results. The software and
      configurations were implemented and have been applied in studies of ten patients.
      The creation of the study protocol required the involvement of various
      professionals and interdepartmental cooperation. The introduction of the protocol
      has ended previously recurrent involvement of staff in the file transfer phase
      and improved cost-effectiveness. 

PMID- 25617093
TI  - [Aneuploidies in oocytes used in IVF programs].
AB  - The aim of the study was to investigate with FISH the frequency of aneuploidies
      of the first and second polar bodies (PB-I and PB-II) of oocytes in women
      participating in IVF programs. The study included 93 women, 82 of them were after
      controlled ovulation stimulation (COS), 11 in natural cycles. FISH in 238 PB-I
      and PB-II was done. Revealed that the frequency of aneuploidies in oocytes after
      COS was higher than in the natural cycle, and also was higher after COS in women
      with infertility compared to women stimulated because of male infertility and
      donors of oocytes. Aneuploidies of oocytes after COS are more common in patients
      after 35 years old. Thus, the study of aneuplodies of PB-I and PB-II by FISH is
      an informative tool of pregestation genetic diagnosis. 

PMID- 25617094
TI  - [Anesthetic aspects of brain dislocation syndrome].
AB  - The article presents a comparative analysis of the proposed methods of intensive
      care to eliminate/reduce the development of syndrome of displacement of the brain
      during neurosurgical operations with known and accepted algorithms and
      recommendations. The aim of this work was the detailed specification of the
      activities of the anesthesiologist with the introduction of some moments in the
      existing algorithms for minimizing the negative effects of the dislocation of the
      brain at the stage of decompression of the cranial cavity during neurosurgical
      operations. Analyzed intraoperative period at runtime techniques in 49 patients
      during operations regarding severe closed craniocerebral injury complicated by
      the formation of subdural and epidural hematomas. In a comparative aspect between
      groups there were no statistically significant differences in the results of
      blood pressure and heart rate dynamics (for hemodynamic stabilization), but a
      more rapid effect was achieved within the temporary components in patients
      surveyed group. The use of low volume correction by stream introduction of
      crystalloid and colloid solutions followed by introduction of saluretics with the
      parallel change of narcosis and simultaneous short-term "acute" hyperventilation
      with minimal doses of sympathomimetics infusion allows for a relatively short
      time to stabilize hemodynamics and reduce the development of syndrome of
      displacement of the brain.

PMID- 25617095
TI  - [The dynamics of changes in rheological properties of oral fluid in patients with
      different levels of oral hygiene, using removable dentures].
AB  - The issue of changing the physical and physico-chemical characteristics of oral
      fluid and their dependence on the level of oral hygiene in patients with
      removable dentures, requires further study. Therefore, in 86 individuals with 138
      removable dentures, and 34 patients who are dentally and somatically healthy, we
      have had studied the parameters of viscosity, velocity of salivation, pH and
      concentration of mucin. According to the results of the factor analysis, it was
      determined that 78.6% of the studied parameters were indicators of hygienic
      condition of oral cavity. On the basis of significant difference and the strength
      and direction of correlation between the studied parameters and values of the
      integral index of oral hygiene, it was found, that in patients without somatic
      pathology with proper oral hygiene, we observed the growth of the rate of
      salivation and pH(c1), and in case of improper hygienic condition - reducing rate
      of salivation and increasing concentration of mucin. In case of the presence of
      somatic pathology, with an improvement of oral hygiene, the growth of pH(c1) and
      reducing of concentration of mucin was observed. The deterioration of oral
      hygiene level led to the increase of the rate of viscosity and the reduction of
      the salivation rate.

PMID- 25617096
TI  - [Condition of periodontal tissue in women with bacterial vaginosis].
AB  - Cross colonization of open cavities of human body has little been studied in
      contemporary medicine. There in no practical recommendations as for management of
      dental patients with urogenital tract microflora disorder. The paper presents the
      findings of clinical features of periodontium tissues in women with bacterial
      vaginosis correlated with bacteriological estimation of oral cavity and vagina,
      number of sexual partners. Interpretation of amine test of oral and vaginal
      fluids has been provided for the first time. Chronic generalized inflammatory and
      inflammatory-dystrophic periodontal diseases of different severity have been
      detected in all female patients with gynecological diagnosis of bacterial
      vaginosis. Gardnerella vaginalis, which is atypical representative of oral cavity
      microflora, has been detected by the PCR method in bacterial vaginosis both in
      vagina and oral cavity. The major markers of bacterial vaginosis have been also
      detected in oral cavity in women with this pathology. 

PMID- 25617097
TI  - [Clinical reasoning of impact of contemporary partial dentures constructions on
      the condition of periodontal tissues of patients with generalized periodontitis
      of I-II severity].
AB  - The aim of the study was the evaluation of the effectiveness of using partial
      dentures made of thermoplastic materials for patients with generalized
      periodontitis of I-II degree of severity based on the results of clinical
      research. The effect of partial dentures made of acrylic, metal and thermoplastic
      materials with and without splinting elements of fixation on the state of
      periodontal tissues in patients with generalized periodontitis was studied. The
      results of clinical studies of patients periodontal tissues condition ,who have
      had dental defects on the background I-II severity of GP using partial splinting
      elements of fixation showed a significant improvement in oral hygiene, positive
      change in activity indicators current of generalized periodontitis. The group of
      patients for whom were made orthopedic constructions of thermoplastic masses,
      noticed reducing of the depth of periodontal pockets, tooth mobility, bleeding
      and inflammation of the interdental papillae and the gingival margin. 

PMID- 25617098
TI  - [Features' dental status population of the territory of Ukraine in different
      historical epochs].
AB  - In recent decades, domestic and foreign dentistry actively developing direction
      associated with the study of the ancient population health. As part of this
      special issue of the informative value of acquiring individual are extremely
      fragmented findings of human remains. Therefore the aim of the study was to
      determine the characteristics of the course of dental caries in the historical
      aspect by considering anthropological remains of Ukrainian citizens from copper
      age to the late Middle Ages. During the Bronze Age, Early Iron Age (EIA) in
      adults caries cavities (CC) are fixed at an age close to 40 years and above. In
      the copper age population in Ukraine manual were apparently extremely rare, their
      traces, we have not found. As a continuation of the tightening properties of
      caries in the EIA (except Class II) have already taken place and CC of V class
      (many combinations of class II and V) appear damaged teeth and lost, probably as
      a complication of tooth decay. All of the above prompts to seek new development
      study of the state of skeletal remains. 

PMID- 25617099
TI  - Myocardial dysfunction during septic shock (review).
AB  - Patients with septic shock frequently develop myocardial dysfunction evidenced by
      severely depressed ejection fraction with ventricular dilatation, as measured by
      an increase in mean systolic and end diastolic ventricular volumes. The
      pathophysiology of myocardial dysfunction is complex and involves a multitude of
      factors. The current review describes individual contributing factors and
      mechanisms such as upregulation of proinflammatory cytokines (IL-1, TNFalpha, IL
      2, IL-6, IFN-gamma), reduced myocardial responsiveness to beta-adrenergic
      stimulation, elevated circulating endothelin levels, Impaired calcium uptake and
      release from calcium sarcoplasmic reticulum storage, and decreased calcium
      channel sensitivity, overexpression of inducible NOS and increased production of
      Nitric oxide. We also discuss possible reasons for apparently detrimental effect
      of NO inhibition on cardiovascular function in large clinical trials with sepsis
      patients.

PMID- 25617100
TI  - Studies of troponin I level changes in patients with coronary artery disease
      after percutaneous coronary intervention.
AB  - Research has been carried out in TSMU Cardiology department of A.Aladashvili
      University Clinic involving 150 patients with ischemic heart disease. The changes
      of Tn level before and after percutaneous coronary intervention (PCI) in patients
      with CAD as well as its dependence on the cardiovascular events rate have been
      studied in previous work. In patients with normal Tn I level before and after PCI
      hospital cardiovascular events rate occurred to be as low as the rate of later
      events. Elevated level of Tn I after PCI was associated with increased rate of
      complications, which were mostly appeared in those patients with high level of Tn
      I before PCI. High level of 30-day mortality was revealed in patients with normal
      level of Tn I before PCI, which was elevated after procedure. The highest rate of
      later mortality was demonstrated in patients with high level of Tn I before PCI
      that was sustained after procedure. Hence, on the basis of our data we can
      conclude, that the Tn level before and after PCI has a prognostic significance;
      High level of Tn I before PCI is associated with increased hospitalization and
      later mortality rates. The elevation of Tn I after PCI in patients with normal
      initial level is more significant predictor of early (30-day) mortality compared
      to later (within 12 months) mortality. 

PMID- 25617101
TI  - [Development and optimization of diagnostically informative boichemical and
      coagulative correlators in various atherosclerotic lesions of carotid arteries].
AB  - Diagnostically informative biochemical and coagulative correlators in various
      atherosclerotic lesions of carotid arteries are developed. It has been
      established positive correlation of the degree of stenosis and intima-media
      thickness of carotid arteries with the following biochemical parameters: total
      cholesterol, LDL cholesterol, Apo-B, Lp(a), triglycerides, hs-C-reactive
      protein(CRP), interleukines (IL-1beta and IL-6), fibrinogen, D-dimers. Negative
      correlation was stated with respect to HDL cholesterol, Apo-A-1, protein C. The
      established correlators of carotid intima-medial layer and the studied laboratory
      indices favour their inclusion into carotid atherosclerosis monitoring.

PMID- 25617102
TI  - [Schoolchildren's visual acuity in the dynamics of learning].
AB  - The results of the screening study of the acuity of schoolchildren between 7 and
      17 years old living in Rostov Region of the Russian Federation are discussed in
      the article. The method of computer optometry was used to measure acuity. 93772
      pupils, 48621 girls and 45151 boys, from 150 schools participated in this
      examination. It was found that there is sustained growth of those with low acuity
      (0,2 and less) among children of both sexes from junior group (7 years) to the
      senior (17). The signs of the decline in visual acuity among girls (14%) are
      manifested earlier than in boys (8%). The decline in visual acuity among 7-8-year
      old children is about 3%. While comparing children from rural areas with those
      from big cities a true dependence of the parameter (acuity) on the factors (city
      and sex) was found.

PMID- 25617103
TI  - Wilson disease with thrombocytopenia (case report).
AB  - We present an adolescent patient with WD accompanied with secondary amenorrhea,
      and thrombocytopenia. NK, a 14 year-old girl, had amenorrhea for 5 months despite
      having had regular menses for 2 years. An abdominal ultrasound scan revealed
      ascitis and some ovarian cysts. On physical examination: slight jaundice, edema
      of lower extremities, skin purpuric rash, enlarged abdomen, dry skin. She had no
      hepatomegaly and no splenomegaly. Breast and pubic hair development was
      concomitant with Tanner stage 4. There was performed laboratory and instrumental
      investigations. The patient was diagnosed as WD owing to the low level of
      ceruloplasmin, with increased level of copper in 24-hour urine excretion and in
      dry liver tissue. The needle biopsy of liver showed severe hepatocellular
      necrosis, inflammatory changes and fibrosis. The platelet count was found to be
      low with lack of increased number of megakaryocytes in the bone marrow aspiration
      suggesting the thrombocytopenia was not exclusively owing to hypersplenism. The
      absence of antithrombocyte and other autoimmune and viral antibodies excluded
      respectively the diagnosis of autoimmune thrombocytopenia, other autoimmune
      diseases and viral infections. Thus, we support the recommendation that
      adolescents with amenorrhea or children with thrombocytopenia without any obvious
      cause should be evaluated for WD, because the early detection and treatment of WD
      is capable of reversing described changes and restoring a normal liver function. 

PMID- 25617104
TI  - [The study of quality characteristics of the hydrogel ointments and films based
      on copolymers divinyl esters of diethylene glycol].
AB  - The possibility of using a hydrogel based on divinyl ether co- and terpolymer of
      diethylene glycol as the backbone polymer for incorporating water-soluble
      medicinal substances was examined. The character of the influence of emulsifiers,
      plasticizers, high-boiling liquids and bioactive substances is defined within the
      changes of physical-chemical properties of obtained hydrogels. The obtained
      polyelectrolyte hydrogels by their homogeneity, dehydration and rheological
      characteristics may be of concern in function of matrices to create external
      prolonged-action dosage forms. 

PMID- 25617105
TI  - [Tolerance and safety of drug arglabin].
AB  - The clinical researches were carried out on tolerance and safety of using an
      original medical drug Arglabin in capsules as immunomodulator. By results of
      researches the drug showed good tolerance and safety in healthy volunteers. Drug
      Arglabin in capsules as immunomodulator can be recommend for the further studying
      in the clinical practice. 

PMID- 25617106
TI  - Energy metabolism disorders in rat salivary glands tissues in connection with
      chronic sodium nitrate intoxication.
AB  - The purpose of the research was the study of nitrite impact on energy metabolism
      in salivary gland tissues in connection with chronic nitrate intoxication. The
      study has been carried out on 100 Wistar rats, weighing 160-250 g, which were
      divided into following groups: the 1st group consisted of intact rodents
      (control); the 2nd group consisted of experimental rodents, where chronic nitrate
      intoxication has been reproduced during 14, 30, 60 and 90 days. Intoxication
      leads to hypoxia, which complications cause tissue hypoxia. Has been established
      that prolonged intake of nitrates in low doses leads to their accumulation in
      salivary glands tissues all these result in derangement of metabolism at the
      intermembrane cellular level. At the same time energy metabolism in salivary
      glands is inhibited, resulting in their dysfunction at the excretory and
      endocrine levels. 

PMID- 25617107
TI  - [Dental anatomy of dogs].
AB  - The aim of the research was to investigate dog teeth anatomy as animal model for
      study of etiopathogenesis of caries disease and physiological tooth wear in
      human. After examining the dog's dental system, following conclusions were drawn:
      the dog has 42 permanent teeth, which are distributed over the dental arches not
      equally, and so the upper dentition consists of 20, and the lower of 22 teeth.
      The largest are considered upper fourth premolar and lower first molars, which
      are called discordant teeth. Between discordant teeth and fangs a dog has an open
      bite, which is limited to the top and bottom conical crown premolar teeth. Thus,
      in the closed position of the jaws, behind this occlusion is limited by
      discordant teeth, just in contact are smaller in size two molars. Only large
      dog's molars in a valid comparison can be likened to human molars, which allows
      us to use them in an analog comparison between them with further study of the
      morphological features ensure durability short-crown teeth and their
      predisposition to caries.

PMID- 25617108
TI  - [Problems of reforming pension schemes of the Georgian population].
AB  - Decent level of pension provision for older people is one of the indispensable
      condition of any democratic society. Over time, the objectives pursued by the
      public pension system, have undergone many changes, but remains a constant
      problem preventing poverty of older citizens, and later, ensuring adequate
      standards of living of this, increasing the proportion of citizens. Certainly,
      the question of the relationship of the working population of premiums and
      pensions becomes essential economic and political importance. In the countries
      with transitive economy, which include Georgia, the most vulnerable because
      limited possibilities of pensioners fit into the new economic development.
      Georgia has not yet happened formation sufficiently clear approach to the reform
      of the existing system of social protection, which is characterized by extremely
      high paternalistic role of the state and very poorly marked public institutions.
      The system mainly focuses on targeted, efficient solution of problems of the
      crisis, however, this approach does not provide a long-term effect, because is
      not aimed at preventing repetition of crises on social protection perspective of
      each individual and the population as a whole. It is need creating highly focused
      on society's expectations of a multidisciplinary task of social protection, which
      should provide a comprehensive multifaceted assistance in solving problems
      throughout his life. In this context, social protection should be seen as a
      protection against social risks of loss or limitation of economic independence
      and social well-being. Forms and methods of organization of social protection of
      the elderly should be differentiated, affordable, high-grade, fully oriented to
      the prevention and resolution of the positive ways to separate the individual
      complex emergencies. Requires special consideration problem with the level of
      pensions, the solution of which depends not only on the economy but also on the
      new concept of pensions, which should include the introduction of a funded
      pension.

PMID- 25617109
TI  - [Problems of accessibility for the population of Georgian modern outpatient and
      inpatient care].
AB  - Which began in 2013, the implementation of the priority national project -
      Universal health programs for population of Georgia - has important social
      significance, given the increased accessibility of the population in case of
      timely and quality medical care. Various forms of public participation in the
      payment of services received in varying degrees allow us to find a compromise
      between containment of demand and increase access to treatment. And if the
      insurance in its various forms, largely solves the last problem, but may create a
      problem of rising costs, the different types of direct payments more efficient
      demand, however creates a need to control access to health care for populations
      with a high demand for medical care. Co-payments under the defined government
      programs and directly to the patient, on the one hand, imply severally pay for
      health care and the fear of the occurrence of catastrophic costs of treatment,
      and on the other hand, allow you to control the rising costs of the health
      system. The problem of reducing the availability of medical care is overcome by
      introducing exemptions from co-payments for vulnerable groups, which in turn
      leads to a substantial increase in government spending. It must be emphasized
      that the tools developed and the results of the calculations can be used to
      compare the effects of the introduction of various schemes of co-payments and
      choose the most suitable scheme, in terms of the extent of the burden of private
      expenditure on treatment, as well as income and expenses of the health system in
      general. 

PMID- 25617110
TI  - [Familial Mediterranean Fever in children and adolescents in Georgia].
AB  - There are presented preliminary results of the analysis of the materials of the
      register of children and adolescents suffering from Familial Mediterranean Fever
      in Georgia. The register was created by the "snow ball" method. For today it
      contains data on 138 patients, 56 (40.6%) males, 82 (59.4%) females, 86 (62.3%)
      less than 10 year old, 52 (37.7%) 10-18 year old. Almost in all patients the
      Armenian roots were revealed, both from maternal and paternal sides. Among the
      MEFV gene mutations M694V (mainly) and also V726A and M680I were the most common
      ones.

PMID- 25617111
TI  - Fast cerebellar reflex circuitry requires synaptic vesicle priming by munc13-3.
AB  - Munc13-3 is a member of the Munc13 family of synaptic vesicle priming proteins
      and mainly expressed in cerebellar neurons. Munc13-3 null mutant (Munc13-3 (-/-))
      mice show decreased synaptic release probability at parallel fiber to Purkinje
      cell, granule cell to Golgi cell, and granule cell to basket cell synapses and
      exhibit a motor learning deficit at highest rotarod speeds. Since we detected
      Munc13-3 immunoreactivity in the dentate gyrus, as reported here for the first
      time, and current studies indicated a crucial role for the cerebellum in
      hippocampus-dependent spatial memory, we systematically investigated Munc13-3 (-/
      ) mice versus wild-type littermates of both genders with respect to hippocampus
      related cognition and a range of basic behaviors, including tests for anxiety,
      sensory functions, motor performance and balance, sensorimotor gating, social
      interaction and competence, and repetitive and compulsive behaviors. Neither
      basic behavior nor hippocampus-dependent cognitive performance, evaluated by
      Morris water maze, hole board working and reference memory, IntelliCage-based
      place learning including multiple reversals, and fear conditioning, showed any
      difference between genotypes. However, consistent with a disturbed cerebellar
      reflex circuitry, a reliable reduction in the acoustic startle response in both
      male and female Munc13-3 (-/-) mice was found. To conclude, complete deletion of
      Munc13-3 leads to a robust decrease in the acoustic startle response. This
      readout of a fast cerebellar reflex circuitry obviously requires synaptic vesicle
      priming by Munc13-3 for full functionality, in contrast to other behavioral or
      cognitive features, where a nearly perfect compensation of Munc13-3 deficiency by
      related synaptic proteins has to be assumed. 

PMID- 25617112
TI  - Maternal organism and embryo biosensoring: insights from ruminants.
AB  - In terms of contribution to pregnancy, the mother not only produces gametes, but
      also hosts gestation, whose progression in the uterus is conditioned by early
      events during implantation. In ruminants, this period is associated with
      elongation of the extra-embryonic tissues, gastrulation of the embryonic disk and
      cross-talk with the endometrium. Recent data have prompted the need for accurate
      staging of the bovine conceptus and shown that asynchrony between elongation and
      gastrulation processes may account for pregnancy failure. Data mining of
      endometrial gene signatures has allowed the identification of molecular pathways
      and new factors regulated by the conceptus (e.g. FOXL2, SOCS6). Interferon-tau
      has been recognised to be the major signal of pregnancy recognition, but
      prostaglandins and lysophospholipids have also been demonstrated to be critical
      players at the conceptus-endometrium interface. Interestingly, up-regulation of
      interferon-regulated gene expression has been identified in circulating immune
      cells during implantation, making these factors a potential source of non
      invasive biomarkers for early pregnancy. Distinct endometrial responses have been
      shown to be elicited by embryos produced by artificial insemination, in vitro
      fertilisation or somatic cell nuclear transfer. These findings have led to the
      concept that endometrium is an early biosensor of embryo quality. This biological
      property first demonstrated in cattle has been recently extended and associated
      with embryo selection in humans. Hence, compromised or suboptimal endometrial
      quality can subtly or deeply affect embryo development, with visible and
      sometimes severe consequences for placentation, foetal development, pregnancy
      outcome and the long-term health of the offspring. 

PMID- 25617113
TI  - CT of acute pancreatitis: a matter of time.

PMID- 25617114
TI  - Identification and characterization of 2-keto-3-deoxy-L-rhamnonate dehydrogenase
      belonging to the MDR superfamily from the thermoacidophilic bacterium
      Sulfobacillus thermosulfidooxidans: implications to L-rhamnose metabolism in
      archaea.
AB  - We identified the non-phosphorylated L-rhamnose metabolic pathway (Rha_NMP) genes
      that are homologous to those in the thermoacidophilic archaeon Thermoplasma
      acidophilum in the genome of the thermoacidophilic bacterium Sulfobacillus
      thermosulfidooxidans. However, unlike previously known 2-keto-3-deoxy-L
      rhamnonate (L-KDR) dehydrogenase (KDRDH) which belongs to the short chain
      dehydrogenase/reductase superfamily, the putative KDRDHs in S.
      thermosulfidooxidans (Sulth_3557) and T. acidophilum (Ta0749) belong to the
      medium chain dehydrogenase/reductase (MDR) superfamily. We demonstrated that
      Sulth_3559 and Sulth_3557 proteins from S. thermosulfidooxidans function as L
      rhamnose dehydrogenase and KDRDH, respectively. Sulth_3557 protein is an NAD(+)
      specific KDRDH with optimal temperature and pH of 50  degrees C and 9.5,
      respectively. The K m and V max values for L-KDR were 2.0 mM and 12.8 U/mg,
      respectively. Sulth_3557 also showed weak 2,3-butanediol dehydrogenase activity.
      Phylogenetic analysis suggests that Sulth_3557 and its homologs form a new
      subfamily in the MDR superfamily. The results shown in this study imply that
      thermoacidophilic archaea metabolize L-rhamnose to pyruvate and L-lactate by
      using the MDR-family KDRDH similarly to that of the thermoacidophilic bacterium
      S. thermosulfidooxidans.

PMID- 25617116
TI  - Keratinolytic Fungi in the Feather Stuffing of a Sofa: A Rare Cause of
      Hypersensitive Pneumonitis.

PMID- 25617115
TI  - Effects of salt on the structure, stability, and function of a halophilic
      dihydrofolate reductase from a hyperhalophilic archaeon, Haloarcula japonica
      strain TR-1.
AB  - The effects of salt on the structure, stability, and enzymatic function of a
      novel dihydrofolate reductase (HjDHFR P1) from a hyperhalophilic archaeon,
      Haloarcula japonica strain TR-1 living in a Japanese saltern, were studied using
      ultraviolet absorption, circular dichroism (CD), and fluorescence spectroscopy.
      HjDHFR P1 had a partial structure at pH 8.0 in the absence of NaCl, and the
      addition of NaCl (0-500 mM concentration) induced significant structural
      formation to HjDHFR P1. The addition of NADPH, which is a coenzyme for its
      catalytic reaction, and lowering the pH from 8 to 6 also induced the same CD
      change, indicating the formation of the NADPH-binding site in HjDHFR P1. The NaCl
      dependence of thermal and urea-induced unfolding measurements suggested that
      protein stability increased depending on NaCl concentration regardless of
      structural formation, and HjDHFR P1 achieved the same stability as Escherichia
      coli DHFR at 750 mM NaCl. Halophilic characteristics were also observed for
      enzymatic function, although its structure had already formed under the
      conditions that enzymatic activity was measured at due to the presence of NADPH.
      These results suggest that the halophilic mechanism on structural stability and
      function was caused by factors other than structural formation, which are
      suggested to be the contributions of preferential interactions between the
      protein and salt ions and the specific binding of salt ions.

PMID- 25617117
TI  - In silico characterization of binding mode of CCR8 inhibitor: homology modeling,
      docking and membrane based MD simulation study.
AB  - Human CC-chemokine receptor 8 (CCR8) is a crucial drug target in asthma that
      belongs to G-protein-coupled receptor superfamily, which is characterized by
      seven transmembrane helices. To date, there is no X-ray crystal structure
      available for CCR8; this hampers active research on the target. Molecular basis
      of interaction mechanism of antagonist with CCR8 remains unclear. In order to
      provide binding site information and stable binding mode, we performed modeling,
      docking and molecular dynamics (MD) simulation of CCR8. Docking study of biaryl
      ether-piperidine derivative (13C) was performed inside predefined CCR8 binding
      site to get the representative conformation of 13C. Further, MD simulations of
      receptor and complex (13C-CCR8) inside dipalmitoylphosphatidylcholine lipid
      bilayers were performed to explore the effect of lipids. Results analyses showed
      that the Gln91, Tyr94, Cys106, Val109, Tyr113, Cys183, Tyr184, Ser185, Lys195,
      Thr198, Asn199, Met202, Phe254, and Glu286 were conserved in both docking and MD
      simulations. This indicated possible role of these residues in CCR8 antagonism.
      However, experimental mutational studies on these identified residues could be
      effective to confirm their importance in CCR8 antagonism. Furthermore, calculated
      Coulombic interactions represented the crucial roles of Glu286, Lys195, and
      Tyr113 in CCR8 antagonism. Important residues identified in this study overlap
      with the previous non-peptide agonist (LMD-009) binding site. Though, the non
      peptide agonist and currently studied inhibitor (13C) share common substructure,
      but they differ in their effects on CCR8. So, to get more insight into their
      agonist and antagonist effects, further side-by-side experimental studies on both
      agonist (LMD-009) and antagonist (13C) are suggested. 

PMID- 25617118
TI  - Reliance on luck: identifying which achievement goals elicit superstitious
      behavior.
AB  - People often resort to superstitious behavior to facilitate goal achievement. We
      examined whether the specific type of achievement goal pursued influences the
      propensity to engage in superstitious behavior. Across six studies, we found that
      performance goals were more likely than learning goals to elicit superstitious
      behavior. Participants were more likely to engage in superstitious behavior at
      high than at low levels of chronic performance orientation, but superstitious
      behavior was not influenced by chronic learning orientation (Studies 1 and 2).
      Similarly, participants exhibited stronger preferences for lucky items when
      primed to pursue performance goals rather than learning goals (Studies 3 and 4).
      As uncertainty of goal achievement increased, superstitious behavior increased
      when participants pursued performance goals but not learning goals (Study 5).
      Finally, assignment to use a lucky (vs. unlucky) item resulted in greater
      confidence of achieving performance goals but not learning goals (Study 6). 

PMID- 25617120
TI  - Clinical implications of prescribing nonsteroidal anti-inflammatory drugs in oral
      health care--a review.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), including both the traditional
      nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are
      widely used for their anti-inflammatory and analgesic effects. They are routinely
      prescribed in dental practice for the management of pain and swelling. Their use
      in treating acute dental pain and chronic orofacial pain, as adjuncts to the
      treatment of periodontal disease, and to minimize edema following surgical
      procedures is well documented. However, long-term utilization of nonselective
      NSAIDs could increase the risk of gastrointestinal symptoms, ranging from mild
      (e.g., dyspepsia, nausea, or vomiting) to serious gastric problems (e.g., gastric
      bleeding or perforation). Therefore, selective COX-2 inhibitors have been
      developed with fewer GI side effects but the recently identified cardiovascular
      adverse reactions limit their routine use in dental practice. Another major
      concern for oral physicians is NSAID-induced mucosal lesions and prolongation of
      bleeding time during invasive dental procedures. This article reviews therapeutic
      and analgesic uses of NSAIDs in dentistry. The various issues surrounding NSAID
      induced adverse reactions and their implications in dentistry are also discussed.

PMID- 25617119
TI  - Efficacy and safety of a new oral saliva equivalent in the management of
      xerostomia: a national, multicenter, randomized study.
AB  - OBJECTIVE AND STUDY DESIGN: The clinical efficacy, safety, and acceptability of a
      new oral saliva equivalent (Novasial) administered four times daily in the
      treatment of xerostomia in various medical conditions was compared with that of
      oxygenated glycerol triester oral spray (Aequasyal) and a moisturizing spray
      (Biotene) in a 2-week, multicenter, randomized, crossover study. Assessment
      included patient-based evaluation of mouth dryness score (primary endpoint) with
      a visual analog scale (VAS), blinded assessment of the oral tissue condition by a
      four-point ordinal scale, and patient-based assessment of tolerability and
      acceptability. RESULTS: At day 14, Novasial decreased oral mouth dryness by
      19.5%, (12.5 +/- 22.6 mm, P < .0001 versus baseline), versus 10% (6.6 +/- 17.9 mm
      with Aequasyal, P < .0001 versus Baseline; and P < .0156 versus Novasial) and 13%
      (8.6 +/- 18.9 mm) with Biotene (P < .0001 versus baseline). The 50% decrease in
      the primary endpoint was not achieved, and the overall efficacy of Novasial and
      Aequasyal were similar with respect to xerostomia. Novasial was preferred to
      Aequasyal and Biotene in alleviating taste alteration and chewing difficulty.
      Treatment compliance was higher with Novasial (P = .0014 versus Aequasyal). The
      treatments improved the oral condition with equal efficacy and were safe and well
      tolerated (VAS 72-77 mm). CONCLUSIONS: Novasial was a safe, well-tolerated, and
      acceptable treatment in patients with xerostomia induced by various treatments or
      pathologic conditions.

PMID- 25617121
TI  - Comparison of phytoncide with sirolimus as a novel drug candidate for drug
      eluting stent.
AB  - A drug-eluting stent (DES) is one of the commonly used treatment techniques in
      percutaneous coronary intervention (PCI). Sirolimus (SRL) has been widely used
      for DES as a drug for suppressing neointimal hyperplasia causing restenosis.
      Phytoncides (PTC) are compounds released from trees and plants, and their
      solutions contain monoterpenoids such as alpha-pinene, careen, and myrceen. Some
      studies have reported that these components exhibit antioxidant, antimicrobial,
      and anti-inflammatory activities. We hypothesized that PTC may become an
      alternative drug to SRL for DES, exhibiting alleviated side effects as compared
      to SRL. A PTC-incorporated stent was compared with an SRL-incorporated stent in
      terms of physicochemical, pharmacokinetic, and biological properties. In in vitro
      studies, the effects of each drug on cells were investigated. The results showed
      that both drugs exhibited similar cytotoxicity, anti-inflammation, and
      antiproliferation effects. However, these effects resulted from different
      mechanisms associated with cells, as seen in the immunofluorescence result. An in
      vivo assay showed that the lumen area was significantly larger and the neointimal
      area was significantly smaller in SRL- and PTC-loaded stents compared to a drug
      unloaded stent. These results suggest that phytoncide can be a feasible
      alternative drug to SRL for advanced DES although more studies are needed.

PMID- 25617122
TI  - Autophagy in SDF-1alpha-mediated DPSC migration and pulp regeneration.
AB  - Critical morphological requirements for pulp regeneration are tissues replete
      with vascularisation, neuron formation, and dentin deposition. Autophagy was
      recently shown to be related to angiogenesis, neural differentiation, and
      osteogenesis. The present study aimed to investigate the involvement of autophagy
      in stromal cell-derived factor-1alpha (SDF-1alpha)-mediated dental pulp stem cell
      (DPSC) migration and pulp regeneration, and identify its presence during pulp
      revascularisation of pulpectomised dog teeth with complete apical closure. In
      vitro studies showed that SDF-1alpha enhanced DPSCs migration and optimised focal
      adhesion formation and stress fibre assembly, which were accompanied by
      autophagy. Moreover, autophagy inhibitors significantly suppressed, whereas
      autophagy activator substantially augmented SDF-1alpha-stimulated DPSCs
      migration. Furthermore, after ectopic transplantation of tooth fragment/silk
      fibroin scaffold with DPSCs into nude mice, pulp-like tissues with vascularity,
      well-organised fibrous matrix formation, and new dentin deposition along the
      dentinal wall were generated in SDF-1alpha-loaded samples accompanied by
      autophagy. More importantly, in a pulp revascularisation model in situ, SDF
      1alpha-loaded silk fibroin scaffolds improved the de novo ingrowth of pulp-like
      tissues in pulpectomised mature dog teeth, which correlated with the punctuated
      LC3 and Atg5 expressions, indicating autophagy. Our findings provide novel
      insights into the pulp regeneration mechanism, and SDF-1alpha shows promise for
      future clinical application in pulp revascularisation.

PMID- 25617123
TI  - Fibroblast adhesion on ECM-derived peptide modified poly(2-hydroxyethyl
      methacrylate) brushes: ligand co-presentation and 3D-localization.
AB  - Polymer brushes prepared via surface-initiated polymerization of 2-hydroxyethyl
      methacrylate are powerful platforms for the fabrication of model biointerfaces to
      study cell-substrate interactions. In this manuscript, the versatility of surface
      initiated polymerization and the poly(2-hydroxyethyl methacrylate) (PHEMA)
      polymer brush platform are used to address two fundamental questions, viz. the
      effects of ligand co-presentation and of the 3D localization of biochemical cues
      on cell behavior. Using a series of PHEMA brushes that present RGD and PHSRN
      ligands in various relative surface concentrations, the present study
      unequivocally demonstrates that: (i) co-presentation of PHSRN cues on an RGD
      functionalized substrate enhances cell adhesion and (ii) this synergetic effect
      is highest when the two ligands are presented at equal surface concentrations. In
      the second part of this study, adhesion of 3T3 fibroblasts on a series of PHEMA
      brushes that present the RGD ligand at a distance of 12, 23 or 42 nm away from
      the cell substrate interface is investigated. While cells were found to adhere to
      surfaces that presented the cell adhesive peptides at distances up to 23 nm from
      the interface, polymer brushes that contained the RGD ligands 42 nm away from the
      interface did not support cell adhesion.

PMID- 25617124
TI  - A dual function of copper in designing regenerative implants.
AB  - The supply of titanium implants which are widely used in orthopaedics with both
      regenerative and anti-microbial properties will achieve a great progress in bone
      regeneration. We asked, whether by appropriate concentrations of copper ions it
      will be possible both to inhibit growth of bacteria and stimulate biological
      responses in mesenchymal stem cells (MSC). Using titanium material which released
      galvanically deposited copper at concentrations from 0.3 to 1.75 mM, growth of
      planktonic Staphylococcus aureus was blocked and more importantly adherent
      bacteria were cleared from the material surface within 24 h. To test biological
      responses of human bone marrow derived MSC due to copper ions, we found that
      copper stimulated the proliferation of MSC in a narrow concentration range around
      0.1 mM. Similar copper concentrations enhanced osteogenic differentiation of MSC
      when cells were cultured in osteogenic differentiation medium. We observed
      increased activity of alkaline phosphatase (ALP), higher expression of collagen
      I, osteoprotegerin, osteopontin and finally mineralization of the cells. We
      conclude that titanium implants that release copper ions can be effective against
      bacterial infections at higher concentrations of copper near the implant surface
      and can promote bone regeneration when its concentration becomes lower due to
      diffusion.

PMID- 25617125
TI  - The antibody atliximab attenuates collagen-induced arthritis by neutralizing
      AIMP1, an inflammatory cytokine that enhances osteoclastogenesis.
AB  - ARS-interacting multifunctional protein 1 (AIMP1) induces production of
      inflammatory cytokines from immune cells. Since osteoclastogenesis is promoted by
      positive regulation of inflammatory cytokines, whether AIMP1 could promote
      osteoclastogenesis was investigated. AIMP1 induced osteoclastogenesis and acted
      synergistically with RANKL to promote osteoclastogenesis. Down-regulation of
      CD23, an AIMP1 receptor, abolished AIMP1-mediated osteoclastogenesis. Enzyme
      linked immunosorbent assays showed that the AIMP1 level was significantly higher
      in the peripheral blood (PB) and synovial fluid of rheumatoid arthritis patients
      than in normal PB. A monoclonal antibody (clone 15B3AF) that blocked the cytokine
      activity of AIMP1 inhibited the AIMP1-mediated production of inflammatory
      cytokines. Clone 15B3AF inhibited the AIMP1-mediated osteoclastogenesis in vitro.
      We then cloned the complementary determining regions of clone 15B3AF and
      generated a chimeric antibody (atliximab). In a collagen-induced arthritis mouse
      model (CIA), atliximab administration significantly attenuated disease severity
      and improved various histopathological parameters. Three-dimensional micro
      computed tomography scanning confirmed that atliximab enhanced the joint
      structures in CIA mice. Furthermore, atliximab decreased the expression of
      inflammatory cytokines in the serum and inflamed joints of CIA mice. Taken
      together, our findings suggest that AIMP1 exacerbates RA by promoting
      inflammation and osteoclastogenesis and that atliximab could be developed as a
      therapeutic antibody to target inflammatory diseases, including RA.

PMID- 25617127
TI  - Suppression of hepatocellular carcinoma by baculovirus-mediated expression of
      long non-coding RNA PTENP1 and MicroRNA regulation.
AB  - Long non-coding RNAs (lncRNAs) play regulatory roles in cancers. LncRNA PTENP1 is
      a pseudogene of the tumor suppressor gene PTEN but its roles in hepatocellular
      carcinoma (HCC) have yet to be explored. Here we confirmed that PTENP1 and PTEN
      were downregulated in several HCC cells, thus we constructed Sleeping Beauty (SB)
      based hybrid baculovirus (BV) vectors for sustained PTENP1 lncRNA expression. Co
      transduction of HCC cells with the SB-BV vector expressing PTENP1 elevated the
      levels of PTENP1 and PTEN, which suppressed the oncogenic PI3K/AKT pathway,
      inhibited cell proliferation, migration/invasion as well as induced autophagy and
      apoptosis. The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a,
      which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such
      autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC
      cell behavior and gene networks by miRNA regulation. Injection of the PTENP1
      expressing SB-BV vector into mice bearing HCC tumors effectively mitigated the
      tumor growth, suppressed intratumoral cell proliferation, elicited apoptosis,
      autophagy and inhibited angiogenesis. These data collectively unveiled the
      molecular mechanisms of how PTENP1 repressed the tumorigenic properties of HCC
      cells and demonstrated the potential of the SB-BV hybrid vector for PTENP1 lncRNA
      modulation and HCC therapy.

PMID- 25617128
TI  - Inorganic photosensitizer coupled Gd-based upconversion luminescent
      nanocomposites for in vivo magnetic resonance imaging and near-infrared
      responsive photodynamic therapy in cancers.
AB  - Inorganic photosensitizer coupled Gd-based upconversion luminescent (UCL)
      nanocomposites have potential application for both magnetic resonance imaging
      (MRI) and photodynamic therapy (PDT) of cancers using the light stability and
      biocompatibility of TiO2 inorganic photosensitizer. However, TiO2 inorganic
      photosensitizer could only be excited by ultraviolet (UV) light, which was
      harmful and weakly penetrable in tissues. In this work, folic acid (FA)-targeted
      NaGdF4:Yb/Tm@SiO2@TiO2 nanocomposites (FA-Gd-Si-Ti NPs) were constructed and
      synthesized for both in vivo MRI and near infrared (NIR)-responsive inorganic
      PDT, in which TiO2 component could be excited by NIR light due to the UCL
      performance of NaGdF4:Yb/Tm component converting NIR to UV light. The results
      showed the as-prepared FA-Gd-Si-Ti NPs had good biocompatibility in vitro and in
      vivo. Moreover, MR study indicated that FA-Gd-Si-Ti NPs were good T1-weighted MRI
      contrast agents with high longitudinal relaxivity (r1) of 4.53 mm(-1) s(-1), also
      in vivo MRI of nude mice showed "bright" signal in MCF-7 tumor. Under the
      irradiation of 980 nm laser at the power density of 0.6 W/cm(2) for 20 min, the
      viability of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease
      from about 90 % to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7
      tumor-bearing nude mice model showed that the inhibition ratio of tumors injected
      with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment, compared with
      that of nude mice in control group. Based on the deep penetration of NIR light
      and the good biocompatibility of TiO2 inorganic photosensitizer, the as-prepared
      FA-Gd-Si-Ti NPs could have potential applications in both MRI and NIR-responsive
      PDT of cancers in deep tissues.

PMID- 25617126
TI  - Protease-degradable PEG-maleimide coating with on-demand release of IL-1Ra to
      improve tissue response to neural electrodes.
AB  - Neural electrodes are an important part of brain-machine interface devices that
      can restore functionality to patients with sensory and movement disorders.
      Chronically implanted neural electrodes induce an unfavorable tissue response
      which includes inflammation, scar formation, and neuronal cell death, eventually
      causing loss of electrode function. We developed a poly(ethylene glycol) hydrogel
      coating for neural electrodes with non-fouling characteristics, incorporated an
      anti-inflammatory agent, and engineered a stimulus-responsive degradable portion
      for on-demand release of the anti-inflammatory agent in response to inflammatory
      stimuli. This coating reduces in vitro glial cell adhesion, cell spreading, and
      cytokine release compared to uncoated controls. We also analyzed the in vivo
      tissue response using immunohistochemistry and microarray qRT-PCR. Although no
      differences were observed among coated and uncoated electrodes for inflammatory
      cell markers, lower IgG penetration into the tissue around PEG+IL-1Ra coated
      electrodes indicates an improvement in blood-brain barrier integrity. Gene
      expression analysis showed higher expression of IL-6 and MMP-2 around PEG+IL-1Ra
      samples, as well as an increase in CNTF expression, an important marker for
      neuronal survival. Importantly, increased neuronal survival around coated
      electrodes compared to uncoated controls was observed. Collectively, these
      results indicate promising findings for an engineered coating to increase
      neuronal survival and improve tissue response around implanted neural electrodes.

PMID- 25617129
TI  - Insights into a microwave susceptible agent for minimally invasive microwave
      tumor thermal therapy.
AB  - This work develops a kind of sodium alginate (SA) microcapsules as microwave
      susceptible agents for in vivo tumor microwave thermal therapy for the first
      time. Due to the excellent microwave susceptible properties and low bio-toxicity,
      excellent therapy efficiency can be achieved with the tumor inhibiting ratio of
      97.85% after one-time microwave thermal therapy with ultralow power (1.8 W, 450
      MHz). Meanwhile, the mechanism of high microwave heating efficiency was confirmed
      via computer-simulated model in theory, demonstrating that the spatial
      confinement efficiency of microcapsule walls endows the inside ions with high
      microwave susceptible properties. This strategy offers tremendous potential
      applications in clinical tumor treatment with the benefits of safety,
      reliability, effectiveness and minimally invasiveness.

PMID- 25617130
TI  - Prolonged prevention of retinal degeneration with retinylamine loaded
      nanoparticles.
AB  - Retinal degeneration impairs the vision of millions in all age groups worldwide.
      Increasing evidence suggests that the etiology of many retinal degenerative
      diseases is associated with impairment in biochemical reactions involved in the
      visual cycle, a metabolic pathway responsible for regeneration of the visual
      chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid
      metabolites, especially all-trans-retinal, is considered responsible for
      photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective
      in lowing the concentration of all-trans-retinal within the retina and thus
      prevent retina degeneration in mouse models of human retinopathies. Here we
      achieved prolonged prevention of retinal degeneration by controlled delivery of
      retinylamine to the eye from polylactic acid nanoparticles in Abca4(-/-)Rdh8(-/-)
      (DKO) mice, an animal model of Stargardt disease/age-related macular
      degeneration. Subcutaneous administration of the nanoparticles containing
      retinylamine provided a constant supply of the drug to the eye for about a week
      and resulted in effective prolonged prevention of light-induced retinal
      degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged
      prophylactic treatment of human retinal degenerative diseases, including
      Stargardt disease and age-related macular degeneration.

PMID- 25617131
TI  - Enhanced antitumor efficacies of multifunctional nanocomplexes through knocking
      down the barriers for siRNA delivery.
AB  - Multifunctional nanocomplexes (NCs) consisting of urocanic acid-modified
      galactosylated trimethyl chitosan (UA-GT) conjugates as polymeric vectors,
      poly(allylamine hydrochloride)-citraconic anhydride (PAH-Cit) as charge
      reversible crosslinkers, and vascular endothelial growth factor (VEGF) siRNA as
      therapeutic genes, were rationally designed to simultaneously overcome the
      extracellular, cellular, and intracellular barriers for siRNA delivery. The
      strong physical stability of UA-GT/PAH-Cit/siRNA NCs (UA-GT NCs) at pH 7.4 and
      6.5 endowed protection from massive dilution, competitive ions, and ubiquitous
      nucleases in the blood and tumorous microenvironment. Their internalization into
      hepato-carcinoma cells was facilitated through the recognition of galactose
      receptors, followed by effective escape from endosomes/lysosomes owing to the
      strong buffering capacity of imidazole residues. At the meantime, the
      endosomal/lysosomal acidity triggered the charge reversal of PAH-Cit in UA-GT
      NCs, thus evoking their structural disassembly and subsequently accelerated
      release of siRNA in the cytosol. As a result, robust in vivo performance in terms
      of both gene silencing and tumor inhibition was achieved by UA-GT NCs at a low
      siRNA dose. Moreover, neither histological nor hematological toxicity was
      detected following repeated intravenous administration. Therefore, UA-GT NCs
      potentially served as an efficient and safe candidate in the treatment of
      hepatocellular carcinoma through knocking down the overall barriers for siRNA
      delivery.

PMID- 25617132
TI  - Novel bilayer bacterial nanocellulose scaffold supports neocartilage formation in
      vitro and in vivo.
AB  - Tissue engineering provides a promising alternative therapy to the complex
      surgical reconstruction of auricular cartilage by using ear-shaped autologous
      costal cartilage. Bacterial nanocellulose (BNC) is proposed as a promising
      scaffold material for auricular cartilage reconstruction, as it exhibits
      excellent biocompatibility and secures tissue integration. Thus, this study
      evaluates a novel bilayer BNC scaffold for auricular cartilage tissue
      engineering. Bilayer BNC scaffolds, composed of a dense nanocellulose layer
      joined with a macroporous composite layer of nanocellulose and alginate, were
      seeded with human nasoseptal chondrocytes (NC) and cultured in vitro for up to 6
      weeks. To scale up for clinical translation, bilayer BNC scaffolds were seeded
      with a low number of freshly isolated (uncultured) human NCs combined with
      freshly isolated human mononuclear cells (MNC) from bone marrow in alginate and
      subcutaneously implanted in nude mice for 8 weeks. 3D morphometric analysis
      showed that bilayer BNC scaffolds have a porosity of 75% and mean pore size of 50
      +/- 25 MUm. Furthermore, endotoxin analysis and in vitro cytotoxicity testing
      revealed that the produced bilayer BNC scaffolds were non-pyrogenic (0.15 +/-
      0.09 EU/ml) and non-cytotoxic (cell viability: 97.8 +/- 4.7%). This study
      demonstrates that bilayer BNC scaffolds offer a good mechanical stability and
      maintain a structural integrity while providing a porous architecture that
      supports cell ingrowth. Moreover, bilayer BNC scaffolds provide a suitable
      environment for culture-expanded NCs as well as a combination of freshly isolated
      NCs and MNCs to form cartilage in vitro and in vivo as demonstrated by
      immunohistochemistry, biochemical and biomechanical analyses.

PMID- 25617133
TI  - Synergistic effect of laminin and mesenchymal stem cells on tracheal mucosal
      regeneration.
AB  - Although several studies have been successfully undertaken of tracheal
      reconstruction in terms of the maintaining the framework of the graft, most cases
      of reconstruction failure have resulted from delayed mucosal regeneration. The
      purposes of this study were to evaluate whether laminin-coated asymmetrically
      porous membrane (APM) scaffold enhances mucosal regeneration, to compare the
      mucosalization capability with mesenchymal stem cell (MSC) seeded APM, and to
      determine whether laminin coating and MSC seeding has a synergistic effect on
      mucosal regeneration. We reconstructed the full-thickness anterior tracheal
      defect of 36 New Zealand White rabbits with the APM scaffold. MSCs were isolated
      from the rabbit's inguinal fat. The animals were divided into 4 groups by the
      presence of laminin coating on APM and application of MSC [Group I, -/-
      (laminin/MSC); Group II, -/+; Group III, +/-; Group IV, +/+]. Endoscopy and
      histologic evaluation were performed and the results were compared among the
      groups. The results showed that ciliated columnar epithelium was regenerated
      earlier in groups II and III than in group I. Furthermore, the application of
      laminin and MSC had synergistic effects on tracheal epithelial regeneration.
      These results demonstrate that tracheal reconstruction by laminin-coated APM
      seeded with MSCs is most effective in enhancing tracheal mucosalization, and
      appears to be promising strategy in the regenerative treatment of tracheal
      defects.

PMID- 25617134
TI  - Human neural stem cell intracerebral grafts show spontaneous early neuronal
      differentiation after several weeks.
AB  - Human neural stem cells (hNSCs) hold great promise for the treatment of
      neurological diseases. Considerable progress has been made to induce neural
      differentiation in the cell culture in vitro and upon transplantation in vivo [2]
      in order to explore restoration of damaged neuronal circuits. However, in vivo
      conventional strategies are limited to post mortem analysis. Here, we apply our
      developed first fate mapping platform to monitor neuronal differentiation in vivo
      by magnetic resonance imaging, bioluminescence imaging, and fluorescence imaging.
      Ferritin, Luciferase and GFP under neuronal-specific promoters for immature and
      mature neurons, respectively, were used to generate transgenic hNSCs.
      Differentiation-linked imaging reporter expression was validated in vitro. The
      time profile of spontaneous neuronal maturation after transplantation into mouse
      brain cortex demonstrated early neuronal differentiation within 6 weeks. Fully
      mature neurons expressing synaptogenesis were observed only after three months or
      longer. Our trimodal fate mapping strategy represents a unique non-invasive tool
      to monitor the time course of neuronal differentiation of transplanted stem cells
      in vivo.

PMID- 25617135
TI  - Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in
      Alzheimer's disease mice using magnetic resonance imaging (MRI).
AB  - Diagnosis of Alzheimer's disease (AD) can be performed with the assistance of
      amyloid imaging. The current method relies on positron emission tomography (PET),
      which is expensive and exposes people to radiation, undesirable features for a
      population screening method. Magnetic resonance imaging (MRI) is cheaper and is
      not radioactive. Our approach uses magnetic nanoparticles (MNPs) made of
      superparamagnetic iron oxide (SPIO) conjugated with curcumin, a natural compound
      that specifically binds to amyloid plaques. Coating of curcumin-conjugated MNPs
      with polyethylene glycol-polylactic acid block copolymer and polyvinylpyrrolidone
      by antisolvent precipitation in a multi-inlet vortex mixer produces stable and
      biocompatible curcumin magnetic nanoparticles (Cur-MNPs) with mean diameter <100
      nm. These nanoparticles were visualized by transmission electron microscopy and
      atomic force microscopy, and their structure and chemistry were further
      characterized by X-ray diffraction, thermogravimetric analysis, X-ray
      photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and
      Fourier transform infrared spectroscopy. Cur-MNPs exhibited no cytotoxicity in
      either Madin-Darby canine kidney (MDCK) or differentiated human neuroblastoma
      cells (SH-SY5Y). The Papp of Cur-MNPs was 1.03 * 10(-6) cm/s in an in vitro blood
      brain barrier (BBB) model. Amyloid plaques could be visualized in ex vivo T2*
      weighted magnetic resonance imaging (MRI) of Tg2576 mouse brains after injection
      of Cur-MNPs, and no plaques could be found in non-transgenic mice.
      Immunohistochemical examination of the mouse brains revealed that Cur-MNPs were
      co-localized with amyloid plaques. Thus, Cur-MNPs have the potential for non
      invasive diagnosis of AD using MRI.

PMID- 25617136
TI  - Electrospun scaffolds for multiple tissues regeneration in vivo through
      topography dependent induction of lineage specific differentiation.
AB  - Physical topographic cues from various substrata have been shown to exert
      profound effects on the growth and differentiation of stem cells due to their
      niche-mimicking features. However, the biological function of different
      topographic materials utilized as bio-scaffolds in vivo have not been rigorously
      characterized. This study investigated the divergent differentiation pathways of
      mesenchymal stem cells (MSCs) and neo-tissue formation trigged by aligned and
      randomly-oriented fibrous scaffolds, both in vitro and in vivo. The aligned group
      was observed to form more mature tendon-like tissue in the Achilles tendon injury
      model, as evidenced by histological scoring and collagen I immunohistochemical
      staining data. In contrast, the randomly-oriented group exhibited much
      chondrogenesis and subsequent bone tissue formation through ossification.
      Additionally, X-ray imaging and osteocalcin immunohistochemical staining also
      demonstrated that osteogenesis in vivo is driven by randomly oriented topography.
      Furthermore, MSCs on the aligned substrate exhibited tenocyte-like morphology and
      enhanced tenogenic differentiation compared to cells grown on randomly-oriented
      scaffold. qRT-PCR analysis of osteogenic marker genes and alkaline phosphatase
      (ALP) staining demonstrated that MSCs cultured on randomly-oriented fiber
      scaffolds displayed enhanced osteogenic differentiation compared with cells
      cultured on aligned fiber scaffolds. Finally, it was demonstrated that
      cytoskeletal tension release abrogated the divergent differentiation pathways on
      different substrate topography. Collectively, these findings illustrate the
      relationship between topographic cues of the scaffold and their inductive role in
      tissue regeneration; thus providing an insight into future development of smart
      functionalized bio-scaffold design and its application in tissue engineering.

PMID- 25617137
TI  - Subcellular stretch-induced cytoskeletal response of single fibroblasts within 3D
      designer scaffolds.
AB  - In vivo, cells are exposed to mechanical forces in many different ways. These
      forces can strongly influence cell functions or may even lead to diseases.
      Through their sensing machinery, cells are able to perceive the physical
      information of the extracellular matrix and translate it into biochemical signals
      resulting in cellular responses. Here, by virtue of two-component polymer
      scaffolds made via direct laser writing, we precisely control the cell matrix
      adhesions regarding their spatial arrangement and size. This leads to highly
      controlled and uniform cell morphologies, thereby allowing for averaging over the
      results obtained from several different individual cells, enabling quantitative
      analysis. We transiently deform these elastic structures by a micromanipulator,
      which exerts controlled stretching forces on primary fibroblasts grown in these
      scaffolds on a subcellular level. We find stretch-induced remodeling of both
      actin cytoskeleton and cell matrix adhesions. The responses to static and
      periodic stretching are significantly different. The amount of paxillin and
      phosphorylated focal adhesion kinase increases in cell matrix adhesions at the
      manipulated pillar after static stretching whereas it decreases after periodic
      stretching.

PMID- 25617138
TI  - Characterization and tissue incorporation of cross-linked human acellular dermal
      matrix.
AB  - Here, we describe a novel human acellular dermal matrix (ADM) cross-linked using
      electron beam irradiation. Structural and biomechanical characteristics of the
      human ADM were assessed by infrared spectrometry and uni-axial tensile testing.
      Electron beam irradiation affects collagen secondary structure, which can be
      detected in the amide I spectral region (1660 cm(-1) and 1690 cm(-1)). At doses
      exceeding 25 kGy, cross-linking of the collagen matrix results in a denser, more
      stratified appearance and parallel arrangement, with significantly increased
      tensile strength and elastic modulus. In a micropig model, the implanted ADM
      elicits rapid host cell infiltration and extracellular matrix deposition;
      however, the delayed remodeling resulted in long-term structural integrity.
      Furthermore, mean densities of collagen and elastin, expression of extracellular
      matrix proteins, and microvessel formation within the implanted ADM increased
      significantly, whereas the thickness of the implanted ADM did not decrease during
      the course of the study. Compared with normal adjacent tissue, type I collagen
      mRNA levels in the ADM increased 12-fold at 3 months after implantation, and
      transforming growth factor-beta mRNA levels increased 3.3-fold at 2 months.
      Matrix metalloproteinase (MMP)-1 and MMP-9 mRNA levels were also elevated.
      Collectively, these results demonstrate that the structural and biomechanical
      properties of this novel cross-linked human ADM are adequate for use as a
      biologic tissue substitute.

PMID- 25617140
TI  - An increase in spina bifida cases in Tunisia, 2008-2011.
AB  - BACKGROUND: The term spina bifida refers to a group of neural tube defects that
      result in malformations of the spinal cord and the surrounding vertebrae. Though
      the etiologies of spina bifida remain largely unknown, several risk factors have
      been identified, including feto-maternal characteristics. AIM OF THE STUDY: To
      discover possible underlying reasons for the increase of spina bifida and
      identify intervention targets, an investigation was undertaken comparing spina
      bifida-affected pregnancy notifications in 2008-2011 with notifications in the
      period 1991-1994. METHODS: Characteristics and outcomes of births with spina
      bifida and pregnancy characteristics of mothers were recorded in the medical
      chart. Comparisons of pregnancies affected by a spina bifida in 2008-2011 were
      made with pregnancies affected by a spina bifida in the period 1991-1994.
      Statistical analysis was undertaken using Poisson regression and Chi-squared
      tests. RESULTS: From 1991 through 1994, the prevalence of identified spina bifida
      cases was equal to 0.3/10,000 births compared to 1.6/10,000 births in 2008-2011.
      This increase was statistically significant (P<0.001). The prevalence of females
      was equal to 0.45 per 10,000 births over the period 1991-1994 compared to 1.88
      per 10,000 births during the period 2008-2011. As for males, the prevalence was
      equal to 0.16 per 10,000 births in 1991-1994 compared to 1.88 in 2008-2011. The
      difference was statistically significant (P<0.001) between both genders. A
      mother's age of over 30 years had significant impact on the emergence of spina
      bifida (P=0.02, OR=3.93, CI=1.23-12.47). As well as, maternal blood type was a
      significant risk factor for the appearance of spina bifida (P=0.008). Results
      also had shown that fetal weight and term, gestity and parity were significant
      risk factors for the occurrence of spina bifida (P<0.05).In this study, results
      have been interpreted with caution due to analyses not being adjusted.
      CONCLUSION: This analysis highlighted areas where prevention efforts should be
      strengthened and surveillance data improved.

PMID- 25617139
TI  - Drug Management in the Elderly IBD Patient.
AB  - OPINION STATEMENT: Managing inflammatory bowel disease (IBD) in a world of
      immunomodulators and biologics is complex enough, but managing the elderly IBD
      patient is further confounded by multiple comorbidities, polypharmacy with drug
      drug interactions, and cognitive mobility/motility disturbances. Social and
      insurance coverage issues also always lurk in the background. All of these
      factors summate into a daunting challenge for the clinician. In this review, we
      aim to describe important considerations when prescribing to an elderly patient
      with IBD, taking into account costs of medications, drug interactions, the aging
      body's effect on pharmacokinetics, and the effect of aging on the immune system.
      Adverse effects and drug-drug interactions are expounded upon in detail specific
      for the aging adult with IBD in an effort to assist the clinician in the decision
      making process.

PMID- 25617141
TI  - How Religious Beliefs and Practices Influence the Psychological Health of
      Catholic Priests.
AB  - Roman Catholic diocesan priests are a subgroup of men with unique religious and
      spiritual roles, beliefs, and practices. This qualitative study of 15 priests
      from the mid-Atlantic area of the United States focused on how priests'
      relationship with God and promises of celibacy and obedience influenced their
      psychological health. Using a consensual qualitative research (CQR) design, the
      analysis revealed that participants described their relationship with God as
      central to their health and contributing to positive outcomes (e.g., sense of
      connection and support). The influence of their promises of celibacy and
      obedience were linked to both positive outcomes (e.g., decreased stress, improved
      relationships) and negative outcomes (e.g., internal conflict,
      depression/loneliness). This study highlighted the central role that priests'
      relationship with God has on positive psychological health. Future research is
      necessary to understand how to maximize the positive effects and minimize the
      negative effects of priests' promises of celibacy and obedience, which would
      benefit programs aimed at supporting priests' psychological health.

PMID- 25617144
TI  - Open access (OA) literature: what is it?

PMID- 25617147
TI  - Identification, prevention, and monitoring of the "great obstetrical syndromes".

PMID- 25617146
TI  - Giant cell tumour of bone: new treatments in development.
AB  - Giant cell tumour of bone (GCTB) is a benign osteolytic tumour with three main
      cellular components: multinucleated osteoclast-like giant cells, mononuclear
      spindle-like stromal cells (the main neoplastic components) and mononuclear cells
      of the monocyte/macrophage lineage. The giant cells overexpress a key mediator in
      osteoclastogenesis: the RANK receptor, which is stimulated in turn by the
      cytokine RANKL, which is secreted by the stromal cells. The RANK/RANKL
      interaction is predominantly responsible for the extensive bone resorption by the
      tumour. Historically, standard treatment was substantial surgical resection, with
      or without adjuvant therapy, with recurrence rates of 20-56 %. Studies with
      denosumab, a monoclonal antibody that specifically binds to RANKL, resulted in
      dramatic treatment responses, which led to its approval by the United States Food
      and Drugs Administration (US FDA). Recent advances in the understanding of GCTB
      pathogenesis are essential to develop new treatments for this locally destructive
      primary bone tumour.

PMID- 25617148
TI  - Therapeutic effects of resveratrol in a mouse model of HDM-induced allergic
      asthma.
AB  - Asthma is an inflammatory disease of the lungs characterized by airway remolding.
      In this study, we examined whether resveratrol exerts protective effects on
      allergic asthma in a murine model. To investigate the effects of resveratrol on
      allergic airway inflammation in house dust mite (HDM)-induced mouse asthma and
      explore its mechanism, a chronic asthma mouse model was established by
      intranasally administering extracts of HDM (25MUg of protein in 10MUl of saline)
      for 5days/week for up to 7 consecutive weeks. Resveratrol (50mg/kg body weight),
      dexamethasone (1mg/kg body weight) or a vehicle was administered orally 1h before
      antigen challenges for up to 2weeks. Compared with the HDM-induced mice, the
      level of TNF-alpha of the BALF in the resveratrol+HDM-treated mice had obviously
      decreased. Histological examination of the lung tissue revealed that the
      resveratrol treatments attenuated the fibrotic response and airway inflammation.
      In addition, resveratrol inhibited the expression of the Syk protein and
      degranulation in mast cells. The presented findings collectively suggest that
      resveratrol has a therapeutic effect on mouse allergic asthma, and its mechanism
      of action might be related to reducing the production of the Syk protein. 

PMID- 25617149
TI  - Saikosaponin a inhibits RANKL-induced osteoclastogenesis by suppressing NF-kappaB
      and MAPK pathways.
AB  - Inflammatory cytokines play an important role in osteoclastogenesis. Saikosaponin
      a (SSa) possesses anti-inflammatory activity. However, the role of SSa in
      osteoporosis is still unclear. Therefore, the objective of this study was to
      investigate the effects of SSa on receptor activator of the nuclear factor-kappaB
      ligand (RANKL)-induced osteoclastogenesis and signaling pathway by in vitro
      assay. In mouse bone marrow monocytes (BMMs), SSa suppressed RANKL plus
      macrophage colony-stimulating factor (M-CSF)-induced osteoclast differentiation
      in a dose-dependent manner. Moreover, SSa decreased osteoclastogenesis-related
      marker proteins expression, including NFATc1, c-fos and cathepsin K. At molecular
      levels, SSa inhibited RANKL-induced IkappaBalpha phosphorylation, p65
      phosphorylation and NF-kappaB luciferase activity in RAW264.7 cells. And SSa also
      suppressed RANKL-induced p-38, extracellular signal-regulated kinase (ERK), c-Jun
      N-terminal kinase (JNK) phosphorylation. Taken together, these findings suggest
      that SSa suppresses osteoclastogenesis through inhibiting RANKL-induced p-38,
      ERK, JNK and NF-kappaB activation. SSa is a novel agent in the treatment of
      osteoclast-related diseases, such as osteoporosis. 

PMID- 25617150
TI  - Synthesis, HIV-1 RT inhibitory, antibacterial, antifungal and binding mode
      studies of some novel N-substituted 5-benzylidine-2,4-thiazolidinediones.
AB  - BACKGROUND: Structural modifications of thiazolidinediones at 3rd and 5th
      position have exhibited significant biological activities. In view of the facts,
      and based on in silico studies carried out on thiazolidine-2,4-diones as HIV-1-
      RT inhibitors, a novel series of 2,4-thiazolidinedione analogs have been designed
      and synthesized. METHODS: Title compounds were prepared by the reported method.
      Conformations of the structures were assigned on the basis of results of
      different spectral data. The assay of HIV-1 RT was done as reported by Silprasit
      et al. Antimicrobial activity was determined by two fold serial dilution method.
      Docking study was performed for the highest active compounds by using Glide 5.0.
      RESULTS: The newly synthesized compounds were evaluated for their HIV-1 RT
      inhibitory activity. Among the synthesized compounds, compound 24 showed
      significant HIV-1 RT inhibitory activity with 73% of inhibition with an IC50
      value of 1.31 MUM. Compound 10 showed highest activity against all the bacterial
      strains.A molecular modeling study was carried out in order to investigate the
      possible interactions of the highest active compounds 24, 10 and 4 with the non
      nucleoside inhibitory binding pocket(NNIBP) of RT, active site of GlcN-6-P
      synthase and cytochrome P450 14-alpha-sterol demethylase from Candida albicans
      (Candida P450DM) as the target receptors respectively using the Extra Precision
      (XP) mode of Glide software. CONCLUSION: A series of novel substituted 2-(5
      benzylidene-2,4-dioxothiazolidin-3-yl)-N-(phenyl)propanamides (4-31) have been
      synthesized and evaluated for their HIV-1 RT inhibitory activity, antibacterial
      and antifungal activities. Some of the compounds have shown significant activity.
      Molecular docking studies showed very good interaction.

PMID- 25617151
TI  - Preventive effect of rebamipide on N-methyl-N'-nitro-N-nitrosoguanidine-induced
      gastric carcinogenesis in rats.
AB  - Chemoprevention strategies against gastric cancer (GC) need to be explored in
      light of the fact that stomach cancer still occurs in the absence of Helicobacter
      pylori (HP) infection and following HP eradication. We evaluated the effect of
      rebamipide on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis
      in SD rats. Thirty-nine male rats were divided into four groups based on whether
      or not they were treated with rebamipide and/or MNNG: Control, Rebamipide,
      Control-M, and Rebamipide-M groups. From 8 weeks of age, rats in the Control-M
      and Rebamipide-M groups received MNNG in drinking water for 30 weeks. The
      Rebamipide and Rebamipide-M groups were administered 5mg/kg/day of rebamipide. At
      50 weeks, cancerous lesions were not observed in either the Control or Rebamipide
      groups. Nine rats in the Control-M group had developed GC, while four rats in the
      Rebamipide-M group had developed GC. The incidence of cancer in the Rebamipide-M
      group was significantly less than in the Control-M group (p<0.05), with a trend
      toward a lower incidence of invasive carcinoma in the Rebamipide-M group.
      Carcinomatous invasion into the muscularis propria was not observed in the
      Rebamipide-M group. In conclusion, the present study demonstrates that rebamipide
      suppresses. MNNG-induced carcinogenesis and may also inhibit progression of
      cancer in rats. 

PMID- 25617153
TI  - Orthognathic surgery with or without autologous fat micrograft injection:
      preliminary report on aesthetic outcomes and patient satisfaction.
AB  - Orthognathic surgery leaves the intrinsic volume of the facial soft tissues
      untouched, sometimes resulting in unsatisfactory improvements in aesthetics. The
      aim of this study was to evaluate the aesthetic outcomes and patient satisfaction
      following bimaxillary orthognathic surgery with or without simultaneous facial
      lipofilling procedures. The preoperative and postoperative facial appearances of
      210 patients were compared through analysis of photographs and postoperative
      clinical evaluation. A patient questionnaire was used to assess the perceived
      improvement in aesthetics. One hundred and twenty patients (mean age 20.3 years)
      underwent bimaxillary orthognathic surgery and simultaneous facial lipofilling
      procedures (group I). The remaining 90 patients (mean age 19.8 years) underwent
      skeletal procedures only (group II). The overall aesthetic improvement was
      similar in the two groups (group I 92.5%, group II 91.1%). Greater higher-level
      aesthetic improvement scores were recorded for group I (group I 80%, group II
      55.6%). The overall patient satisfaction was 98.3% for group I and 97.8% for
      group II. Greater higher-level satisfaction scores were recorded for group I
      (group I 14.2%, group II 6.7%). The simultaneous use of the autologous fat
      micrograft is a promising technique that may improve the aesthetic outcomes of
      orthognathic surgery, leading to greater patient satisfaction. 

PMID- 25617152
TI  - CCAAT/enhancer binding protein beta directly regulates the expression of the
      complement component 3 gene in neural cells: implications for the pro
      inflammatory effects of this transcription factor.
AB  - BACKGROUND: The CCAAT/enhancer-binding protein beta (C/EBPbeta) is a
      transcription factor, which was first identified as a regulator of
      differentiation and inflammatory processes mainly in adipose tissue and liver;
      however, its function in the brain was largely unknown for many years. Previous
      studies from our laboratory indicated that C/EBPbeta is implicated in
      inflammatory process and brain injury, since mice lacking this gene were less
      susceptible to kainic acid-induced injury. METHODS: We first performed cDNA
      microarrays analysis using hippocampal RNA isolated from C/EBPbeta (+/+) and
      C/EBPbeta (-/-) mice. Immunocytochemical and immunohistochemical studies were
      done to evaluate C/EBPbeta and C3 levels. Transient transfection experiments were
      made to analyze transcriptional regulation of C3 by C/EBPbeta. To knockdown
      C/EBPbeta and C3 expression, mouse astrocytes were infected with lentiviral
      particles expressing an shRNA specific for C/EBPbeta or an siRNA specific for C3.
      RESULTS: Among the genes displaying significant changes in expression was
      complement component 3 (C3), which showed a dramatic decrease in mRNA content in
      the hippocampus of C/EBPbeta (-/-) mice. C3 is the central component of the
      complement and is implicated in different brain disorders. In this work we have
      found that C/EBPbeta regulates C3 levels in rodents glial in vitro and in the rat
      Substantia nigra pars compacta (SNpc) in vivo following an inflammatory insult.
      Analysis of the mouse C3 promoter showed that it is directly regulated by
      C/EBPbeta through a C/EBPbeta consensus site located at position -616/-599 of the
      gene. In addition, we show that depletion of C/EBPbeta by a specific shRNA
      results in a significant decrease in the levels of C3 together with a reduction
      in the increased levels of pro-inflammatory agents elicited by lipopolysaccharide
      treatment. CONCLUSIONS: Altogether, these results indicate that C3 is a
      downstream target of C/EBPbeta, and it could be a mediator of the pro
      inflammatory effects of this transcription factor in neural cells.

PMID- 25617154
TI  - A pilot study to evaluate the feasibility of individualized yoga for inpatient
      children receiving intensive chemotherapy.
AB  - BACKGROUND: Fatigue is an important problem in paediatric cancer patients and
      yoga may be an effective intervention. The primary objective was to determine the
      feasibility of individualized yoga for hospitalized children receiving intensive
      chemotherapy. METHODS: We included English-speaking children and adolescents aged
      7-18 years receiving intensive chemotherapy or haematopoietic stem cell
      transplantation (HSCT). Yoga was conducted three times weekly for three weeks.
      The primary outcome was feasibility, defined as ability to deliver at least 60%
      of planned sessions. Secondary outcomes were parent-reported Pediatric Quality of
      Life Inventory (PedsQL) Multidimensional Fatigue Scale, Fatigue Scale-Parent,
      PedsQL Generic Core Scales and PedsQL Acute Cancer Module. RESULTS: Between
      January and October 2013, 11 patients were enrolled. Median age was 14.0 (range
      7.7-16.4) years and 6 (55%) were boys. Yoga was feasible with 10/11 participants
      meeting the threshold for feasibility. The median number of yoga sessions was 9
      (range 3-13). No adverse events were attributed to yoga. Mean+/-standard
      deviation for the day 21 proxy-reported PedsQL general fatigue scores was 55.6+/
      15.5. Qualitative comments suggested design changes for future yoga studies.
      CONCLUSIONS: Individualized yoga is feasible for inpatient children receiving
      intensive chemotherapy. Future work will include development and conduct of a
      randomized trial for fatigue amelioration. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02105389.

PMID- 25617156
TI  - Postoperative myelopathy by undiagnosed cervical spine stenosis.

PMID- 25617155
TI  - Intermediate-term results of partial plantar fascia release with microtenotomy
      using bipolar radiofrequency microtenotomy.
AB  - Plantar fasciitis is a common condition, with most patients treated successfully
      with nonoperative management. Recalcitrant disease has been managed with surgical
      procedures that vary in design and associated morbidity. The present study sought
      to determine the intermediate-term results of percutaneous bipolar radiofrequency
      microtenotomy in recalcitrant plantar fasciitis. The patient medical records were
      reviewed, and data were gathered for all the patients who met the inclusion
      criteria. The foot function index and visual analog scale (VAS) pain scale
      questionnaires were mailed to the 111 patients. Of the 111 patients, 61 (55.0%)
      returned their questionnaires and were ultimately included in the present
      analysis. Of the 61 patients, 44 (72.1%) were female and 17 were (27.9%) male,
      with an average reported follow-up of 33.3 +/- 8.6 (range 16.1 to 46.6) months.
      The median postoperative VAS score was 0.0 (range 0.0 to 10.0), and the median
      foot function index score was 3.1 (range 0.0 to 97.1). The patients were
      subdivided into success and failure groups according to their satisfaction. Of
      the 61 patients, 51 (83.6%) were satisfied and would recommend the procedure to a
      friend. The median VAS score in the success group was 0.0 (range 0.0 to 5.0), and
      the median VAS score in the failure group was 6.0 (range 0.0 to 10.0), a
      significant difference (p < .001). A significant difference was also seen in the
      foot function index score between the success (median 2.4, range 0.0 to 25.7) and
      failure (median 37.4, range 0.0 to 97.1) groups (p < .001). Bipolar
      radiofrequency microtenotomy appears to be a safe procedure that can provide
      outcomes equivalent to those with open surgery, with less morbidity, for
      recalcitrant plantar fasciitis. 

PMID- 25617157
TI  - Unilateral bronchospasm during one-lung ventilation.

PMID- 25617158
TI  - Perioperative management and outcome of patients with Rett syndrome undergoing
      scoliosis surgery: a retrospective review.
AB  - BACKGROUND: Rett syndrome is a rare genetically inherited neuromuscular disorder
      exclusively affecting female patients. Progressive scoliosis is one of the main
      features of the disease and affected individuals are very likely to need spine
      correction surgery. METHODS: We undertook a retrospective notes review of
      patients with Rett syndrome who had undergone spine surgery from 2005 to 2013.
      Patients were identified through the hospital's electronic records. The aim of
      the present study was to identify the anesthetic implications encountered and the
      perioperative adverse events, in an effort to improve perioperative management
      and reduce complications. RESULT: We identified twenty-four children who had 29
      procedures in total in this period. Frequent chest infections and poorly
      controlled epilepsy were the main preoperative findings. There were no adverse
      events during induction and intubation. Common anesthetic/analgesic drugs were
      used throughout. Postoperatively, gastrointestinal and respiratory tract
      complications were the most common. Mean intensive care unit stay was 8.1 days
      and mean time to discharge from hospital was 26.5 days. We had one in-hospital
      death. CONCLUSIONS: Our case series demonstrates a high incidence of
      complications in this subpopulation, mainly postoperative. Extreme postoperative
      vigilance is required and recovery in a high dependency unit is highly
      recommended.

PMID- 25617159
TI  - Effects of dexmedetomidine and propofol on sedation in patients after coronary
      artery bypass graft surgery in a fast-track recovery room setting.
AB  - PURPOSE: We aim to compare the effects of propofol and dexmedetomidine infusions
      on extubation times, hemodynamic and respiratory functions, complication rates
      and patient satisfaction scores in patients undergoing coronary artery bypass
      graft (CABG) surgery using a fast-track anesthesia regimen for early extubation.
      METHODS: We enrolled 64 patients who underwent CABG surgery. Dexmedetomidine (min
      0.2 ug/kg/h-max 1.0 ug/kg/h) and propofol (min 1.0 mg/kg/h-max 3.0 mg/kg/h)
      infusion doses were titrated to give bispectral index values between 60 and 90
      and a Ramsay sedation score (RSS) between 3 and 4. Postoperative extubation
      times, patient satisfaction and postoperative adverse events were recorded.
      RESULTS: The mean times to extubation were 265.94 +/- 43.1 min for the
      dexmedetomidine group and 322.52 +/- 39.2 min for the propofol group (P < 0.001).
      In all recordings, RSS median values for the propofol group were significantly
      lower than the dexmedetomidine group (P < 0.05). There were no differences in the
      incidence of postoperative adverse events between the dexmedetomidine and
      propofol groups. There was a statistically significant difference between patient
      satisfaction median values of the two groups-7 (5-9) and 9 (7-10) (min-max) for
      the propofol and dexmedetomidine groups, respectively (P < 0.001). CONCLUSION:
      Our results show that dexmedetomidine can easily be preferred over propofol in
      fast-track cardiac anesthesia due to its significant advantages of shorter
      extubation time and higher postoperative patient satisfaction scores.

PMID- 25617160
TI  - The authors reply to comments on "The lymphocyte transformation test for the
      diagnosis of Lyme borreliosis has currently not been shown to be clinically
      useful." Clin Microbiol Infect 2014;20:O786-O787.

PMID- 25617161
TI  - Effects of leptin on FSH cells in the pituitary gland of Podarcis siculus.
AB  - Leptin is the hormone synthesised by adipocytes, which plays an important role in
      regulating appetite and metabolism. In mammals, this pleiotropic hormone also
      plays a key role in controlling gonadotropin secretion by stimulatory
      hypothalamic and pituitary actions. However, little is known about leptin in
      lower vertebrates and particularly few studies are available on reptiles. In the
      present work, we analysed the action of recombinant human leptin on FSH cells in
      the pituitary gland of Podarcis siculus female lizards exposed to four different
      concentrations of the hormone. FSH cells showed a dose-dependent reaction. The
      data are indicative of the role played by leptin in modulating the cellular
      activity of such cells in the pituitary gland of P. siculus, similar to what was
      already reported in mammals. A functional receptor is evidently able to respond
      to leptin in this lizard, but further comparative studies are needed to
      understand the role of this hormone in ectothermic vertebrates. 

PMID- 25617162
TI  - Erratum to: Effects of partial inhibition of respiratory complex I on H2O2
      production by isolated brain mitochondria in different respiratory states.

PMID- 25617163
TI  - IL-10 and IL-1beta mediate neuropathic-pain like behavior in the ventrolateral
      orbital cortex.
AB  - Previous evidence has shown that the glial cells can be activated by peripheral
      nerve injury and release both pro-inflammatory and anti-inflammatory cytokines,
      which play crucial roles in the establishment and maintenance of neuropathic
      pain. The present study examined the roles of anti-inflammatory cytokine IL-10
      and pro-inflammatory IL-1beta on allodynia induced by spared nerve injury (SNI)
      in the ventrolateral orbital cortex (VLO) in the rat. The mechanical paw
      withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection
      of IL-10 (0.1, 0.5, 1 MUg/0.5 MUl) into the VLO, contralateral to the site of
      nerve injury attenuated allodynia; PWT increased in a dose-dependent manner.
      Similar to IL-10, administration of rabbit anti-rat IL-1beta antibody (0.1, 1.0
      and 10 ng/0.5 MUl) into the same VLO site also alleviated allodynia with a dose
      dependent fashion. Moreover, western blotting results showed expression levels of
      IL-10 and IL-1beta significantly up-regulated in the contralateral VLO of SNI
      rats as compared with that of sham-operated rats. These results suggest that anti
      inflammatory cytokine IL-10 and pro-inflammatory cytokine IL-1beta mediate
      neuropathic-pain like behavior at the cerebral cortex level; IL-10 released from
      activated glial cells in the VLO can potentially attenuate allodynia while IL
      1beta released from activated glial cells in the VLO can potentially maintain or
      facilitate allodynia. These results provide new insights and site for therapy at
      the cerebral cortex level in neuropathic pain condition.

PMID- 25617164
TI  - Capsule commentary on Gidwani et al., CMS reimbursement reform and the incidence
      of hospital-acquired pulmonary embolism or deep vein thrombosis.

PMID- 25617165
TI  - Increased Risk of Mortality among Patients Cared for by Physicians with Short
      Length-of-Stay Tendencies.
AB  - BACKGROUND: Since the introduction of the prospective payment system in 1983,
      U.S. hospitals have been financially incentivized to reduce inpatient length of
      stay, and average length of stay has shortened dramatically. OBJECTIVE: The
      purpose of this study was to determine whether short length of stay is associated
      with worse patient outcomes. DESIGN: We used a quasi-experimental design to
      compare the outcomes of admissions assigned to physicians with short versus long
      length-of-stay tendencies. We used each physician's mean length of stay to define
      their length of stay tendency. We then compared the outcomes of admissions
      assigned to physicians with short versus long length-of-stay tendencies in
      propensity score-matched and adjusted analyses using mixed-effects and
      conditional logistic regression models. PATIENTS: The study included all
      admissions for 10 common diagnoses among patients admitted to the medical
      teaching service of an urban academic hospital from 7/1/2002 through 6/30/2008.
      MAIN MEASURE: The primary outcome was 30-day mortality. RESULTS: We examined
      12,341 admissions among 79 physicians. After propensity score matching, admission
      groups were similar with respect to all demographic and clinical characteristics.
      Admissions of patients receiving care from short length-of-stay physicians were
      associated with significantly increased risk of 30-day mortality in adjusted (OR
      1.43, 95 % CI: 1.11-1.85), propensity score-matched (OR 1.33, 95 % CI: 1.08
      1.63), and matched and adjusted analyses (OR 1.36, 95 % CI: 0.98-1.90).
      CONCLUSIONS: Policies that incentivize short length of stay may lead to worse
      patient outcomes. The financial benefits of shortening inpatient length of stay
      should be weighed against the potential harm to patients.

PMID- 25617167
TI  - Hormone replacement strategies in adult endocrine disease.

PMID- 25617166
TI  - A Patient Navigator Intervention to Reduce Hospital Readmissions among High-Risk
      Safety-Net Patients: A Randomized Controlled Trial.
AB  - BACKGROUND: Evidence-based interventions to reduce hospital readmissions may not
      generalize to resource-constrained safety-net hospitals. OBJECTIVE: To determine
      if an intervention by patient navigators (PNs), hospital-based Community Health
      Workers, reduces readmissions among high risk, low socioeconomic status patients.
      DESIGN: Randomized controlled trial. PARTICIPANTS: General medicine inpatients
      having at least one of the following readmission risk factors: (1) age >=60
      years, (2) any in-network inpatient admission within the past 6 months, (3)
      length of stay >=3 days, (4) admission diagnosis of heart failure, or (5) chronic
      obstructive pulmonary disease. The analytic sample included 585 intervention
      patients and 925 controls. INTERVENTIONS: PNs provided coaching and assistance in
      navigating the transition from hospital to home through hospital visits and
      weekly telephone outreach, supporting patients for 30 days post-discharge with
      discharge preparation, medication management, scheduling of follow-up
      appointments, communication with primary care, and symptom management. MAIN
      MEASURES: The primary outcome was in-network 30-day hospital readmissions.
      Secondary outcomes included rates of outpatient follow-up. We evaluated outcomes
      for the entire cohort and stratified by patient age >60 years (425
      intervention/584 controls) and <=60 years (160 intervention/341 controls). KEY
      RESULTS: Overall, 30-day readmission rates did not differ between intervention
      and control patients. However, the two age groups demonstrated marked
      differences. Intervention patients >60 years showed a statistically significant
      adjusted absolute 4.1% decrease [95% CI: -8.0%, -0.2%] in readmission with an
      increase in 30-day outpatient follow-up. Intervention patients <=60 years showed
      a statistically significant adjusted absolute 11.8% increase [95% CI: 4.4%,
      19.0%] in readmission with no change in 30-day outpatient follow-up. CONCLUSIONS:
      A patient navigator intervention among high risk, safety-net patients decreased
      readmission among older patients while increasing readmissions among younger
      patients. Care transition strategies should be evaluated among diverse
      populations, and younger high risk patients may require novel strategies.

PMID- 25617168
TI  - Optimal glucocorticoid replacement in adrenal insufficiency.
AB  - Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare
      diseases, including primary adrenal insufficiency, secondary adrenal
      insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid
      therapy was introduced over 60 years ago, but since then a number of advances in
      treatment have taken place. Specifically, little is known about short- and long
      term treatment effects, and morbidity and mortality. Over the past decade,
      systematic cohort and registry studies have described reduced health-related
      quality of life, an unfavourable metabolic profile and increased mortality in
      patients with adrenal insufficiency, which may relate to unphysiological
      glucocorticoid replacement. This has led to the development of new modes of
      replacement that aim to mimic normal glucocorticoid physiology. Here, evidence
      for the inadequacy of conventional glucocorticoid therapy and recent developments
      in treatment are reviewed, with an emphasis on primary adrenal insufficiency. 

PMID- 25617169
TI  - Mineralocorticoid substitution and monitoring in primary adrenal insufficiency.
AB  - Patients with primary adrenal insufficiency usually show pronounced impairment of
      aldosterone secretion and, therefore, require also mineralocorticoid replacement
      for full recovery. Clinical signs of mineralocorticoid deficiency comprise
      hypotension, weakness, salt craving and electrolyte disturbances (hyperkalemia,
      hyponatremia). Mineralocorticoid deficiency is confirmed by demonstration of
      profoundly decreased aldosterone and highly elevated plasma renin activity (PRA).
      Standard replacement consists of 9alpha-fluorocortisol (fludrocortisone) given
      once daily as a single oral dose (0.05-0.2 mg). Monitoring of mineralocorticoid
      replacement consists of clinical assessment (well-being, physical examination,
      blood pressure, electrolyte measurements) and measurement of PRA aiming at a PRA
      level in the upper normal range. Current replacement regimens may often be
      associated with mild hypovolemia. Dose adjustments are frequently needed in
      pregnancy to compensate for the anti-mineralocorticoid activity of progesterone
      and in high ambient temperature to avoid sodium depletion. In arterial
      hypertension a dose reduction is usually recommended, but monitoring for
      hyperkalemia is required. 

PMID- 25617170
TI  - Is DHEA replacement beneficial in chronic adrenal failure?
AB  - Although dehydroepiandrosterone (DHEA) and its sulphate ester
      dehydroepiandrosterone sulphate (DHEAS) are the most abundant steroid hormones in
      the human circulation, its exact physiological role is not yet fully understood.
      In patients with adrenal insufficiency, secretion of DHEA is impaired, leading to
      decreased circulating DHEA and DHEAS levels, and to androgen deficiency in women.
      Replacement of DHEA in patients with adrenal insufficiency positively influence
      mood, sexuality and subjective health status. These effects are generally
      moderate and show high inter-individual variability. Limited evidence exists for
      immunomodulatory effects of DHEA. Although an increase of IGF-I levels has been
      documented, relevant effects on body composition, metabolic or cardiovascular
      parameters has not been observed in patients with adrenal insufficiency receiving
      DHEA. Larger-scale phase III studies are still lacking; therefore, initiation of
      DHEA replacement is decided on an individual basis, focussing on those patients
      with impaired well-being associated with signs and symptoms of androgen
      deficiency. 

PMID- 25617171
TI  - Substitution therapy in adult patients with congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive inherited
      disorders caused by defective steroidogenesis. Steroid 21-hydroxylase deficiency
      (21OHD) is its most prevalent form, accounting for over 90% of all cases.
      Clinically classic 21OHD is characterised by glucocorticoid deficiency and
      adrenal androgen excess with (salt wasting form) or without (simple virilising
      form) additional mineralocorticoid deficiency. Life-saving glucocorticoid
      substitution therapy has been available since the 1950s and enables long-term
      survival, and potentially, a good quality of life. However, care of adult
      patients with classic congenital adrenal hyperplasia is challenging for two main
      reasons: firstly, there is no glucocorticoid preparation available mimicking
      circadian cortisol release and adaptation to stress and secondly, management of
      adult patients is still in its infancy. There is no evidence-based treatment and
      experienced centres, taking care of larger patient cohorts, are only emerging. In
      this article we aim to guide physicians on the treatment and monitoring of adult
      patients with 21OHD, based on the clinical studies available and our own clinical
      experience. 

PMID- 25617172
TI  - Parathyroid hormone therapy for hypoparathyroidism.
AB  - Hypoparathyroidism is a disease characterized by hypocalcemia and insufficient
      parathyroid hormone (PTH). It is a rare disorder that has been given an orphan
      disease designation in the United States and European Union. Hypoparathyroidism
      is the only endocrine deficiency disease for which the missing hormone, PTH, is
      not yet an approved therapy. Conventional therapy includes calcium and active
      vitamin D supplementation, often in large doses. Although serum calcium can be
      controlled with conventional therapy, it can be a challenge and, moreover, does
      not address other aspects of the disease, such as abnormal skeletal features and
      reduced quality of life. This review focuses on PTH replacement therapy in
      hypoparathyroidism, utilizing the full-length molecule PTH(1-84) as well as the
      fully active but truncated form PTH(1-34). PTH therapy addresses some aspects of
      the disease not ameliorated with conventional therapy. 

PMID- 25617173
TI  - Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine
      plus L-triiodothyronine.
AB  - At present, the drug of choice for the treatment of hypothyroidism is
      levothyroxine sodium, even though the thyroid gland secretes both thyroxine and
      3',3,5-triiodothyronine; the latter is the more active of the two at the cellular
      level because of its higher affinity for the nuclear thyroid hormone receptors.
      To date, combined levothyroxine plus liothyronine treatment for hypothyroidism
      has been evaluated in 15 clinical trials in humans. In two studies, combined
      therapy seemed to have beneficial effects on mood, quality of life, and
      psychometric performance of patients, compared with levothyroxine alone; in some
      of these studies, the patients preferred levothyroxine plus liothyronine
      combinations. This preference should be balanced against the possibility of
      adverse events resulting from the addition of liothyronine to levothyroxine.
      Until clear advantages of levothyroxine plus liothyronine are demonstrated, the
      administration of levothyroxine alone should remain the treatment of choice for
      replacement therapy of hypothyroidism. 

PMID- 25617174
TI  - Current topics in testosterone replacement of hypogonadal men.
AB  - All forms of hypogonadism - primary, secondary and late-onset - require
      testosterone substitution. The indication is given when the patient presents with
      symptoms of androgen deficiency and the serum testosterone levels are below
      normal. Several testosterone preparations and modes of application are available
      of which those producing physiologic serum levels should be preferred e.g.
      preferentially transdermal gels and long-acting intramuscular testosterone
      undecanoate. Testosterone substitution must be monitored at regular intervals,
      best at 3, 6 and 12 months after initiation and then annually. Parameters for
      surveillance include well-being, libido and sexual activity, measurement of serum
      testosterone levels, haemoglobin and haematocrit, PSA and digital rectal
      examination, and, biannually, bone mineral density. Testosterone has positive
      effects on comorbidities such as obesity, metabolic syndrome, diabetes type II,
      cardiovascular diseases and osteoporosis. 

PMID- 25617175
TI  - Gonadotrophin replacement for induction of fertility in hypogonadal men.
AB  - Congenital hypogonadotrophic hypogonadism (CHH) is a rare form of infertility
      caused by deficient secretion or action of gonadotrophin-releasing hormone. There
      is no consensus regarding the optimal approach to fertility treatment in CHH men.
      In most cases, appropriate hormonal treatment with human chorionic gonadotrophin
      with or without follicle stimulating hormone will induce testicular development,
      spermatogenesis and fertility. Recent studies have examined sequential treatment
      with FSH pre-treatment to optimize fertility outcomes in severely affected CHH
      patients. This paper reviews historical and recent literature to summarize the
      current evidence on therapeutic approaches for CHH men seeking fertility. 

PMID- 25617176
TI  - Sex hormone replacement in ovarian failure - new treatment concepts.
AB  - Premature ovarian failure is associated with decreased bone mass and fractures,
      and an increased risk of premature death from cardiovascular disease. There is
      also fertility compromise associated not only with the loss of ovarian function
      but, in those with pre-pubertal POF, inadequate uterine morphology. A wide
      variety of hormone replacement regimes are reported, but there is no clear
      evidence of best practice. Hormone replacement therapy (HRT) and the combined
      oral contraceptive pill (COCP) will suppress menopausal symptoms; however neither
      is designed to achieve physiological replacement of oestrogen and progesterone.
      There is evidence that physiological sex steroid replacement is superior to
      standard hormone replacement, in improving uterine volume as well as an improved
      blood pressure profile and bone mineral density. Sex steroid replacement therapy
      is long-term in these women, and therefore it is essential that the risk benefit
      ratio is optimal to maximise longer term health. 

PMID- 25617177
TI  - Growth hormone replacement in adults - current standards and new perspectives.
AB  - Growth hormone deficiency (GHD) in adults is an established clinical syndrome
      characterised by adverse body composition with more body fat than lean body mass,
      unfavourable blood lipids, decreased physical fitness and poor quality of life.
      No specific biomarker for GHD exists and the sometimes difficult diagnosis should
      be made in accordance with, established guidelines. Measurements of insulin-like
      growth factor I (IGF-I) is often not sufficient for the diagnosis and stimulation
      tests of the GH reserve are required. After diagnosis of GHD, treatment with GH
      should be initiated with a low dose, and gradually increased aiming at obtaining
      an IGF-I level within the upper part of the normal range for age matched healthy
      controls. Most side effects are mild and transient and attenuated by gradual dose
      increments. Numerous studies have shown that GH treatment can improve body
      composition, cardiovascular risk factors, physical capacity and quality of life.
      However, studies on effects beyond 5 years are few and despite encouraging
      preliminary reports the ultimate endpoint demonstrating that GH treatment has
      beneficial effects on mortality, cardiovascular events and fractures without an
      increase in cancer incidence remain to be solidly demonstrated and studies to
      resolve these issues are awaited. Trials with long acting GH formulations are
      ongoing and available data indicate similar effects on outcome measures compared
      to the effects of daily injections. This review will give an overview of
      clinically relevant issues of GHD including advice for management of these
      patients. 

PMID- 25617178
TI  - Achiral-chiral two-dimensional chromatography of free amino acids in milk: A
      promising tool for detecting different levels of mastitis in cows.
AB  - In two-dimensional HPLC (2D-HPLC) "heart-cut" applications, two columns are
      connected in series via a switching valve and volume fractions from the "primary"
      column are re-injected on the "secondary" column. The heart-cut 2D-HPLC system
      here described was implemented by connecting a reversed-phase (RP) column (first
      dimension) to a chiral column (second dimension) containing a quinidine-based
      chiral stationary phase. The system was used to evaluate the change in the
      enantiomeric excess value of dansylated (Dns) amino acids (AAs) in milk samples
      from two cows with different "California Mastitis Test" scores: negative test for
      sample 1, positive for sample 2. Apart from the co-elution of Dns-Arg/Dns-Gly and
      the reduced chemoselectivity for Dns-Leu/Dns-allo-Ile, the optimized achiral RP
      method distinguished the remaining standard Dns-AAs. Dns-AAs were identified in
      the chromatograms of the real samples, and in higher concentration Dns-Ala, Dns
      Arg, Dns-Asp, Dns-Glu, Dns-Ile, Dns-Leu, Dns-Phe and Dns-Val. Except Dns-Arg, the
      chiral column enabled the RP enantioseparation of all the other compounds (alpha
      and RS values up to 1.65 and 8.63, respectively, for Dns-Phe). In sample 2, the
      amounts of Dns-d-AAs were rather elevated, in particular for Dns-Ala and Dns-Asp.
      Instead, for sample 1, D-isomers were detected for Dns-Ala, Dns-Glu and Dns-Leu.
      The proposed 2D-HPLC method could be useful for the identification of clinical
      mastitis difficult to be diagnosed. Moreover, the eventual progressive reduction
      of D-AAs levels with the degree of sub-clinical mastitis could allow the building
      of mathematical models to use for the diagnosis of early stages of mastitis.

PMID- 25617179
TI  - PEGylated D-serine dehydratase as a D-serine reducing agent.
AB  - D-Serine is an endogenous coagonist for N-methyl-D-aspartate (NMDA) receptors and
      is involved in excitatory neurotransmission. Excessive receptor activation causes
      excitotoxicity, leading to various acute and chronic neurological disorders.
      Decrease in D-serine content may provide a therapeutic strategy for the treatment
      of the neurological disorders in which overstimulation of NMDA receptors plays a
      pathological role. Saccharomyces cerevisiaed-serine dehydratase (Dsd1p), which
      acts dominantly on D-serine, may be a useful D-serine reducing agent. We
      conjugated a linear 5-kDa polyethylene glycol (PEG) to Dsd1p (PEG-Dsd1p) and
      examined the effects of PEG-conjugation on its biochemical and pharmacokinetic
      properties. PEG-Dsd1p retained activity, specificity, and stability of the
      enzyme. The PEG modification extended the serum half-life of Dsd1p in mice 6
      fold, from 3.8h to 22.4h. PEG-Dsd1p was much less immunogenic compared to the
      unmodified enzyme. Intraperitoneal administration of PEG-Dsd1p was effective in
      decreasing the D-serine content in the mouse hippocampus. These findings suggest
      that PEG-Dsd1p may be a novel tool for lowering D-serine levels in vivo.

PMID- 25617180
TI  - Identifying hospitalized pediatric patients for early discharge planning: a
      feasibility study.
AB  - A screening tool utilized by nurses at a critical point in the discharge planning
      process has the potential to improve caregiver decisions and enhance
      communication. The Early Screen for Discharge Planning-Child version (ESDP-C)
      identifies pediatric patients early in their hospital stay who will benefit from
      early engagement of a discharge planner. This study used a quasi-experimental,
      non-equivalent comparison group design to evaluate the impact of the ESDP-C on
      important outcomes related to discharge planning. Findings from the study provide
      preliminary evidence that the integration of the ESDP-C into the pediatric
      discharge planning process may be clinically useful. 

PMID- 25617181
TI  - A genetic-demographic approach reveals a gender-specific association of
      SLC6A3/DAT1 40 bp-VNTR with life-expectancy.
AB  - Several recent lines of evidence are proving an important role for dopamine in
      the aging process and in the determination of life span. Components of the
      dopaminergic system may represent good candidates for longevity studies. Herein,
      we tested the possible association of the functional SLC6A3/DAT1 40-bp VNTR with
      life-expectancy in a healthy population of Central Italy (N = 993) by applying a
      genetic-demographic approach that takes into account the demographic information
      and different survival rates between sexes for modeling the survival of specific
      allele carriers in the population. Male carriers of S*/S* genotype showed a lower
      survival chance across most of the lifespan respect to the survival of DAT1*L
      carriers (P = 0.021). The same analyses gave non-significant results in females.
      Several studies already reported significant sex differences in dopamine
      metabolism and its related biological pathways. Thus, we can hypothesize that the
      SLC6A3/DAT1 40 bp-VNTR may affect life expectancy in a sex-specific way.
      Moreover, it is conceivable that DAT1 S*/S* carriers, who are prone to assume
      "risk" type behaviors, may be dropped out of the "healthy" population by a sort
      of "demographic selection".

PMID- 25617182
TI  - Opioid misuse among adolescents: new evidence from a misclassification analysis.
AB  - BACKGROUND: Non-medical prescription-opioid (NMPO) use has been declared a
      national epidemic in the US. Opioid misuse is associated with substantial
      physiological, psychological, and concomitant economic implications. NMPO use
      among adolescents warrants special attention given its prevalence and the high
      risk of addiction. OBJECTIVES: Our objectives were to: (a) identify factors
      associated with adolescent NMPO use after controlling for misclassification,
      while simultaneously identifying characteristics that affected the likelihood of
      misreporting use; and (b) identify factors associated with an individual misusing
      their own versus a diverted prescription, and the likelihood that the
      prescription source was misreported. METHODS: Data come from the Washington State
      Healthy Youth Survey. A maximum likelihood estimation technique for
      systematically misclassified binary-dependent variables was utilized. Covariates
      were chosen to represent influential factors identified in the theoretical
      adolescent development literature. RESULTS: An estimated 35 % of respondents who
      stated that they had never misused prescription opioids most likely had. An
      estimated 17 % of those who admitted to NMPO use claimed to have misused a
      diverted prescription, but most likely misused their own. Various demographic,
      school, neighborhood, family, substance-use, personality/attitude, and social
      factors were identified as potential predictors of adolescent NMPO use, opioid
      prescription source, and misclassification of responses to each outcome.
      CONCLUSIONS: The finding that a self-reported survey failed to identify over one
      third of individuals at risk for NMPO use is concerning, as is the finding that
      approximately 17 % of those who admitted to NMPO use may have misstated their
      prescription-opioid source. The findings presented here are critical to focus
      prevention efforts, especially for identifying at-risk youths who may
      misrepresent their use.

PMID- 25617183
TI  - Enzyme-assisted supercritical carbon dioxide extraction of black pepper oleoresin
      for enhanced yield of piperine-rich extract.
AB  - Black pepper (Piper nigrum L.), the King of Spices is the most popular spice
      globally and its active ingredient, piperine, is reportedly known for its
      therapeutic potency. In this work, enzyme-assisted supercritical carbon dioxide
      (SC-CO2) extraction of black pepper oleoresin was investigated using alpha
      amylase (from Bacillus licheniformis) for enhanced yield of piperine-rich extract
      possessing good combination of phytochemical properties. Optimization of the
      extraction parameters (without enzyme), mainly temperature and pressure, was
      conducted in both batch and continuous modes and the optimized conditions that
      provided the maximum yield of piperine was in the batch mode, with a sample size
      of 20 g of black pepper powder (particle diameter 0.42 +/- 0.02 mm) at 60 
      degrees C and 300 bar at 2 L/min of CO2 flow. Studies on activity of alpha
      amylase were conducted under these optimized conditions in both batch and
      continuous modes, with varying amounts of lyophilized enzyme (2 mg, 5 mg and 10
      mg) and time of exposure of the enzyme to SC-CO2 (2.25 h and 4.25 h). The
      specific activity of the enzyme increased by 2.13 times when treated in the
      continuous mode than in the batch mode (1.25 times increase). The structural
      changes of the treated enzymes were studied by (1)H NMR analyses. In case of
      alpha-amylase assisted extractions of black pepper, both batch and continuous
      modes significantly increased the yields and phytochemical properties of piperine
      rich extracts; with higher increase in batch mode than in continuous.

PMID- 25617184
TI  - Anaerobic co-digestion of kitchen waste and pig manure with different mixing
      ratios.
AB  - Anaerobic co-digestion of kitchen waste (KW) and pig manure (PM) with seven
      different PM to KW total solids (TS) ratios of 1:0, 5:1, 3:1, 1:1, 1:3, 1:5 and
      0:1 was conducted at mesophilic temperature (35 +/- 1  degrees C) to investigate
      the feasibility and process performance. The co-digestion of PM and KW was found
      to be an available way to enhance methane production compared with solo-digestion
      of PM or KW. The ratio of PM to KW of 1:1 got the highest biodegradability (BDA)
      of 85.03% and a methane yield of 409.5 mL/gVS. For the co-digestion of KW and PM,
      there was no obvious inhibition of ammonia nitrogen because it was in an
      acceptable range from 1380 mg/L to 2020 mg/L in the whole process. However,
      severe methane inhibition and long lag phase due to the accumulation of volatile
      fatty acids (VFAs) was observed while the KW content was over 50%, and in the lag
      phase, propionic acid and butyric acid made up the major constituents of the
      total VFAs. The technical digestion time (T80: the time it takes to produce 80%
      of the digester's maximum gas production) of the above 7 ratios was 15, 21, 22,
      27, 49, 62 and 61 days, respectively. In this study, a mixing ratio of 1:1 for PM
      and KW was found to maximize BDA and methane yield, provided a short digestion
      time and stable digestion performance and was therefore recommended for further
      study and engineering application.

PMID- 25617185
TI  - [Can a recognized human carcinogen such as radon be healthy?].

PMID- 25617186
TI  - Chlorpyrifos degradation in soils with different treatment regimes within Nzoia
      River Drainage Basin, Kenya.
AB  - Two organic amendments, filter mud compost and Tithonia diversifolia leaves
      generated within a sugarcane growing area were used to enhance the degradation of
      chlorpyrifos in soil. Filter mud compost and T. diversifolia leaves significantly
      enhanced degradation of chlorpyrifos in soils (p < 0.05) with DT50 values of 21
      and 24 days, respectively. Furthermore, field degradation of chlorpyrifos in soil
      with prior exposure to chlorpyrifos was significantly enhanced (p = 0.034) with
      DT50 of 21 days compared to 30 days in soil with no previous exposure.
      Degradation of chlorpyrifos in sterile and non-sterile soils were significantly
      different (p = 0.023) with DT50 values of 161 and 27 days, respectively. Results
      show enhanced degradation of chlorpyrifos in organically amended soils and soils
      with prior exposure to the pesticide. These amendments show promise in a
      continuing effort to reduce chlorpyrifos concentrations in soils.

PMID- 25617187
TI  - Familial congenital bilateral vocal fold paralysis: a novel gene translocation.
AB  - OBJECTIVES: True vocal fold (TVF) paralysis is a common cause of neonatal stridor
      and airway obstruction, though bilateral TVF paralysis is seen less frequently.
      Rare cases of familial congenital TVF paralysis have been described with implied
      genetic origin, but few genetic abnormalities have been discovered to date. The
      purpose of this study is to describe a novel chromosomal translocation
      responsible for congenital bilateral TVF immobility. METHODS: The charts of three
      patients were retrospectively reviewed: a 35 year-old woman and her two children.
      The mother had bilateral TVF paralysis at birth requiring tracheotomy. Her oldest
      child had a similar presentation at birth and also required tracheotomy, while
      the younger child had laryngomalacia without TVF paralysis. Standard karyotype
      analysis was done using samples from all three patients and the parents of the
      mother, to assess whether a chromosomal abnormality was responsible. RESULTS:
      Karyotype analysis revealed the same balanced translocation between chromosomes 5
      and 14, t(5;14) (p15.3, q11.2) in the mother and her two daughters. No other
      genetic abnormalities were identified. Neither maternal grandparent had the
      translocation, which appeared to be a spontaneous mutation in the mother with
      autosomal dominant inheritance and variable penetrance. CONCLUSIONS: A novel
      chromosomal translocation was identified that appears to be responsible for
      familial congenital bilateral TVF paralysis. While there are other reports of
      genetic abnormalities responsible for this condition, we believe this is the
      first describing this particular translocation.

PMID- 25617188
TI  - A pilot study investigating basic fibroblast growth factor for the repair of
      chronic tympanic membrane perforations in pediatric patients.
AB  - OBJECTIVE: A pilot study to investigate the utility of basic Fibroblast Growth
      Factor (bFGF) in tympanic membrane perforation (TMP) closure in a small cohort of
      pediatric patients. METHODS: Prospective cohort study. Suitability for inclusion
      in the study was confirmed by the application of defined inclusion and exclusion
      criteria, and informed parental consent obtained. The technique used was a
      modification of the bFGF-technique by Kanemaru et al. Response to treatment was
      monitored with serial otoscopy and audiometric outcomes were determined.
      Statistical analysis of the outcomes was carried out. RESULTS: TMPs were
      successfully closed in 7/12 children at the first attempt (58%) and in 10/12
      children overall (83%). Hearing improvement was observed in 8/10 successfully
      treated cases (80%). There were no complications or adverse outcomes.
      CONCLUSIONS: The topical bFGF regeneration technique offers a promising,
      minimally invasive alternative to conventional myringoplasty in pediatric
      patients with comparable success and reduced morbidity and cost, especially
      considering the option of performing repeat applications. Patients with an active
      infection or inflammation are not suitable for the bFGF-mediated technique.

PMID- 25617189
TI  - Hearing rehabilitation with the closed skin bone-anchored implant Sophono Alpha1:
      results of a prospective study in 15 children with ear atresia.
AB  - OBJECTIVE: To study gain and cutaneous tolerance of the Sophono Alpha1 implant,
      used for unilateral hearing rehabilitation in children with ear atresia, and to
      demonstrate non-inferiority compared to the referral closed skin device, BAHA(r)
      on a test-band. METHODS AND MATERIALS: Fifteen children included in a prospective
      clinical trial from September 2010 to November 2012. Tertiary care center. MAIN
      OUTCOMES: Pure tone and speech audiometry before surgery and at M6 and 12; Speech
      in-noise tests with and without Alpha1 at M6. Quality of life questionnaire
      completed before surgery and at M6; children and parent's satisfaction assessed
      at M6. Cutaneous appearance assessed at M6, M12 and during the last clinical
      assessment. RESULTS: Patients' ages ranged from 61 to 129 months. They had a pure
      conductive deafness with a mean air conduction pure-tone average (ACPTA) of
      69.02+/-9.31dB, and a mean SRT of 71.73+/-9.20dB. Follow-up was 12-32 months. At
      M6, the mean aided ACPTA was 33.49+/-4.89dB, the mean aided SRT 38.27+/-4.54dB
      and the mean aided SRT in noise was statistically improved (-7.80dB). Sophono
      Alpha1 demonstrated non-inferiority compared to BAHA(r) on a test-band. At M12,
      mean aided ACPTA was 2.94dB higher (p<0.001) but the mean SRT variation (+0.73dB)
      was not significantly different (p=0.35). At M12, all children used the implant 5
      to 12h daily (mean: 10) without cutaneous complications. Both children and
      parents reported being satisfied or very satisfied. The score for 7/10 questions
      in silence or noisy environment was statistically improved when wearing the
      device. CONCLUSIONS: This prospective study demonstrate non inferiority, good
      cutaneous tolerance, satisfaction of children and parents and improvement of the
      quality of life with the Sophono Alpha1 compared to BAHA(r) on a test-band. In
      the light of this study and of the previously published series, the aided
      threshold is between that obtained with BAHA on a softband and percutaneous BAHA.
      The Sophono Alpha1 device needs to be part of the hearing solutions proposed for
      the hearing rehabilitation in children with ear atresia.

PMID- 25617191
TI  - All about the money.

PMID- 25617190
TI  - Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in
      Laos: a prospective study.
AB  - BACKGROUND: Scrub typhus (caused by Orientia tsutsugamushi), murine typhus
      (caused by Rickettsia typhi), and leptospirosis are common causes of febrile
      illness in Asia; meningitis and meningoencephalitis are severe complications.
      However, scarce data exist for the burden of these pathogens in patients with CNS
      disease in endemic countries. Laos is representative of vast economically poor
      rural areas in Asia with little medical information to guide public health
      policy. We assessed whether these pathogens are important causes of CNS
      infections in Laos. METHODS: Between Jan 10, 2003, and Nov 25, 2011, we enrolled
      1112 consecutive patients of all ages admitted with CNS symptoms or signs
      requiring a lumbar puncture at Mahosot Hospital, Vientiane, Laos. Microbiological
      examinations (culture, PCR, and serology) targeted so-called conventional
      bacterial infections (Streptococcus pneumoniae, Neisseria meningitidis,
      Haemophilus influenzae, S suis) and O tsutsugamushi, Rickettsia typhi/Rickettsia
      spp, and Leptospira spp infections in blood or cerebrospinal fluid (CSF). We
      analysed and compared causes and clinical and CSF characteristics between patient
      groups. FINDINGS: 1051 (95%) of 1112 patients who presented had CSF available for
      analysis, of whom 254 (24%) had a CNS infection attributable to a bacterial or
      fungal pathogen. 90 (35%) of these 254 infections were caused by O tsutsugamushi,
      R typhi/Rickettsia spp, or Leptospira spp. These pathogens were significantly
      more frequent than conventional bacterial infections (90/1051 [9%] vs 42/1051
      [4%]; p<0.0001) by use of conservative diagnostic definitions. CNS infections had
      a high mortality (236/876 [27%]), with 18% (13/71) for R typhi/Rickettsia spp, O
      tsutsugamushi, and Leptospira spp combined, and 33% (13/39) for conventional
      bacterial infections (p=0.076). INTERPRETATION: Our data suggest that R
      typhi/Rickettsia spp, O tsutsugamushi, and Leptospira spp infections are
      important causes of CNS infections in Laos. Antibiotics, such as tetracyclines,
      needed for the treatment of murine typhus and scrub typhus, are not routinely
      advised for empirical treatment of CNS infections. These severely neglected
      infections represent a potentially large proportion of treatable CNS disease
      burden across vast endemic areas and need more attention. FUNDING: Wellcome Trust
      UK.

PMID- 25617192
TI  - A door-to-door approach to cervical cancer screening.

PMID- 25617193
TI  - Child pneumonia at a time of epidemiological transition.

PMID- 25617194
TI  - Rickettsioses as causes of CNS infection in southeast Asia.

PMID- 25617195
TI  - Weak health systems and Ebola.

PMID- 25617196
TI  - Hepatitis C drug affordability.

PMID- 25617197
TI  - The Global Fund in China: success beyond the numbers.

PMID- 25617198
TI  - Association between economic growth and early childhood nutrition.

PMID- 25617199
TI  - Association between economic growth and early childhood nutrition--authors'
      reply.

PMID- 25617200
TI  - Falsified medicines in Africa.

PMID- 25617201
TI  - Cost-effectiveness of Xpert MTB/RIF and investing in health care in Africa.

PMID- 25617202
TI  - Effect of self-collection of HPV DNA offered by community health workers at home
      visits on uptake of screening for cervical cancer (the EMA study): a population
      based cluster-randomised trial.
AB  - BACKGROUND: Control of cervical cancer in developing countries has been hampered
      by a failure to achieve high screening uptake. HPV DNA self-collection could
      increase screening coverage, but implementation of this technology is difficult
      in countries of middle and low income. We investigated whether offering HPV DNA
      self-collection during routine home visits by community health workers could
      increase cervical screening. METHODS: We did a population-based cluster
      randomised trial in the province of Jujuy, Argentina, between July 1, 2012, and
      Dec 31, 2012. Community health workers were eligible for the study if they scored
      highly on a performance score, and women aged 30 years or older were eligible for
      enrolment by the community health worker. 200 community health workers were
      randomly allocated in a 1:1 ratio to either the intervention group (offered women
      the chance to self-collect a sample for cervical screening during a home visit)
      or the control group (advised women to attend a health clinic for cervical
      screening). The primary outcome was screening uptake, measured as the proportion
      of women having any HPV screening test within 6 months of the community health
      worker visit. Analysis was by intention to treat. This trial is registered with
      ClinicalTrials.gov, number NCT02095561. FINDINGS: 100 community health workers
      were randomly allocated to the intervention group and 100 were assigned to the
      control group; nine did not take part. 191 participating community health workers
      (94 in the intervention group and 97 in the control group) initially contacted
      7650 women; of 3632 women contacted by community health workers in the
      intervention group, 3049 agreed to participate; of 4018 women contacted by
      community health workers in the control group, 2964 agreed to participate. 2618
      (86%) of 3049 women in the intervention group had any HPV test within 6 months of
      the community health worker visit, compared with 599 (20%) of 2964 in the control
      group (risk ratio 4.02, 95% CI 3.44-4.71). INTERPRETATION: Offering self
      collection of samples for HPV testing by community health workers during home
      visits resulted in a four-fold increase in screening uptake, showing that this
      strategy is effective to improve cervical screening coverage. This intervention
      reduces women's barriers to screening and results in a substantial and rapid
      increase in coverage. Our findings suggest that HPV testing could be extended
      throughout Argentina and in other countries to increase cervical screening
      coverage. FUNDING: Instituto Nacional del Cancer (Argentina).

PMID- 25617203
TI  - Incidence and severity of childhood pneumonia in the first year of life in a
      South African birth cohort: the Drakenstein Child Health Study.
AB  - BACKGROUND: Childhood pneumonia causes substantial mortality and morbidity.
      Accurate measurements of pneumonia incidence are scarce in low-income and middle
      income countries, particularly after implementation of pneumococcal conjugate
      vaccine. We aimed to assess the incidence, severity, and risk factors for
      pneumonia in the first year of life in children enrolled in a South African birth
      cohort. METHODS: This birth cohort study is being done at two sites in Paarl, a
      periurban area of South Africa. We enrolled pregnant women (>18 years) and
      followed up mother-infant pairs to 1 year of age. We obtained data for risk
      factors and respiratory symptoms. Children received 13-valent pneumococcal
      conjugate vaccine according to national immunisation schedules. We established
      pneumonia surveillance systems and documented episodes of ambulatory pneumonia
      and pneumonia warranting hospital admission. We calculated incidence rate ratios
      for pneumonia with mixed-effects Poisson regression. FINDINGS: Between May 29,
      2012 and May 31, 2014, we enrolled 697 infants who accrued 513 child-years of
      follow-up. We recorded 141 pneumonia episodes, with an incidence of 0.27 episodes
      per child-year (95% CI 0.23-0.32). 32 (23%) pneumonia cases were severe
      pneumonia, with an incidence of 0.06 episodes per child-year (95% CI 0.04-0.08).
      Two (1%) of 141 pneumonia episodes led to death from pneumonia. Maternal HIV,
      maternal smoking, male sex, and malnutrition were associated with an increased
      incidence of pneumonia. INTERPRETATION: Pneumonia incidence was high in the first
      year of life, despite a strong immunisation programme including 13-valent
      pneumococcal conjugate vaccine. Incidence was associated with pneumonia risk
      factors that are amenable to interventions. Prevention of childhood pneumonia
      through public health interventions to address these risk factors should be
      strengthened. FUNDING: Bill & Melinda Gates Foundation, South African Thoracic
      Society, Federation of Infectious Diseases Societies of South Africa, and
      University of Cape Town.

PMID- 25617204
TI  - Wilson's disease in association with anetoderma.
AB  - BACKGROUND: Wilson's disease is an autosomal recessive disorder of copper
      homeostasis with predominantly hepatic and neuropsychiatric involvement.
      Anetoderma is a rare benign condition with focal damage of dermal elastic tissue.
      Previous reports described this skin disorder in association with prolonged D
      Penicillamine therapy. CASE PRESENTATION: A 26-year-old male was referred for
      evaluation of asymptomatic elevation of aminotransferase levels. Investigations
      showed negative markers for chronic viral and autoimmune hepatitis, low
      ceruloplasmin level, and increased copper urinary excretion. Liver biopsy
      revealed chronic hepatitis with moderate activity and severe bridging fibrosis.
      Mutation analysis found a compound heterozygote genotype and supported a
      diagnosis of Wilson's disease. At the time of the primary physical exam, skin
      lesions were also observed, consisting of numerous white to pale papules less
      than 7-8 mm in diameter with central protrusion located at the upper part of the
      body. Primary anetoderma was established based on presentation and skin biopsy
      findings. Therapy with D-Penicillamine at a daily dose of 1500 mg was started,
      and, during 12-month follow-up, aminotransferase decreased to normal and skin
      lesions remained unchanged. CONCLUSION: In our opinion the case is a first
      reported association between Wilson's disease and primary anetoderma. The
      possible mechanism behind this relationship is discussed.

PMID- 25617205
TI  - Computer simulation study of the intermolecular structure of phosphoric acid-N,N
      dimethylformamide mixtures.
AB  - The structures and energies of the complexes (H3PO4)2, H3PO4-DMF, and (H3PO4)2
      DMF were analyzed at the B3LYP level of approximation. It was found that H-bonds
      form between H3PO4 and DMF molecules, but the strength of the H-bond depends
      strongly on its molecular environment. Effects of the solvent were taken into
      account via the CPCM approach. According to the B3LYP-SPCM calculations, the
      O...O distance in (H3PO4)2-DMF is shorter and its H-bonds are stronger than in
      the other complexes studied. In order to study the effects of concentration on
      the intermolecular structure, molecular dynamics simulations of H3PO4-DMF
      mixtures with mole fractions of acid of <0.1 were performed. The calculations
      indicated that the largest fraction of the acid protons are involved in hydrogen
      bonding with oxygen atoms of the DMF molecules. An increased probability of acid
      acid hydrogen-bond formation at phosphoric acid mole fractions >0.06 was also
      noted. 

PMID- 25617206
TI  - Hydrogen bridges of polycyclic aromatic systems with O-H...O bonds--a gas-phase
      vs. solid-state Car-Parrinello study.
AB  - The current study belongs to a series of investigations of polycyclic aromatic
      compounds containing intramolecular hydrogen bonds. Close proximity of the
      coupled aromatic system and hydrogen bridges gives rise to resonance-assisted
      hydrogen bonding phenomena. Substituted naphthols are ideally suited for this
      kind of investigation. The parent compound, 1-hydroxy-8-methoxy-3
      methylnaphthalene, and its derivative, 1-bromo-5-hydroxy-4-isopropoxy-7
      methylnaphthalene, both with known crystal structure, are investigated. Car
      Parrinello molecular dynamics (CPMD) is chosen as a theoretical background for
      this study. Gas phase and solid state simulations are carried out. The effect of
      Grimme's dispersion corrections is also included. The report presents time
      evolution of structural parameters, spectroscopic signatures based on the CPMD
      simulations, and comparison with available experimental data. We show that the
      proton transfer phenomena do not occur within the simulations, which is
      consistent with evaluation based on the acidity of the donor and acceptor sites.
      The effects of the substitution in the aromatic system and change of the
      environment (gas vs. condensed phase) are of similar magnitude. 

PMID- 25617208
TI  - Modeling the antiferromagnetic MnIIMnII system within the protein phosphatase-5
      catalytic site.
AB  - Protein phosphatase-5 (PP5), a novel target for inhibition in a search for new
      antitumor drugs, contains a homobimetallic Mn(II)Mn(II) system in its catalytic
      site. The ground electronic state is an antiferromagnetically-coupled singlet. We
      report optimizations of a known inhibitor within a 42-residue model of the PP5
      catalytic site under several two-level hybrid ONIOM computational models. Using
      the high-resolution crystal structure of a PP5/inhibitor complex as reference, we
      compare geometric parameters as the qualities of the "high-level" and "low-level"
      wavefunctions are successively improved by using the correct antiferromagnetic
      (AF) singlet state. We find that the UB3LYP AF wavefunction for the high-level
      region is necessary for experimental fidelity. A closed-shell semi-empirical
      method (RPM6) can be used for the low-quality part of the hybrid scheme to afford
      geometries which are qualitatively on par with that obtained using the more time
      consuming open-shell UB3LYP AF wavefunction. As the AF state can be elusive for
      such a large system, the ferromagnetic (F) state can also be used in the low
      quality calculations without impacting the geometry. 

PMID- 25617207
TI  - Computational studies of water and carbon dioxide interactions with cellobiose.
AB  - B3LYP/6-311++G** with dispersion correction (DFT-D) was used to study local and
      global minimum energy structures of water (H2O) or carbon dioxide (CO2) bonding
      with a pair of cellobiose molecules. The calculations showed that neither the H2O
      nor the CO2 prefer to be between the cellobiose molecules, and that the minimum
      energy structures occur when these molecules bond to the outer surface of the
      cellobiose pair. The calculations also showed that the low energy structures have
      a larger number of inter-cellobiose hydrogen bonds than the high energy
      structures. These results indicate that penetration of H2O or CO2 between
      adjacent cellobiose pairs, which would assist steam or supercritical CO2 (SC-CO2)
      explosion of cellulose, is not energetically favored. Comparison of the energies
      obtained with DFT-D and DFT (the same method but without dispersion correction)
      show that both hydrogen bonds and van der Waals interactions play an important
      role in cellobiose-cellobiose interactions. 

PMID- 25617209
TI  - Nitro and dinitroamino N-oxides of octaazaanthracene as high energy materials.
AB  - The present study undertook the design of nitro and dinitroamino compounds from
      the skeleton of isomeric N-oxides of octaazanaphthalene, using computational
      methods to predict their degradation and explosive characteristics. The atom
      equivalent method was employed to evaluate the gas phase heats of formation of
      the designed species. Condensed phase heats of formation were also determined and
      found to be in the range of 220-286 kcal mol(-1). Crystal densities of all the
      designed molecules were calculated and found to be in the range of 1.91-1.98 g
      cm(-3). Detonation pressure (P) and detonation velocity (D) determined using the
      Kamlet-Jacobs equation showed that the performance of nitro-substituted compounds
      was comparable to that of RDX while that of dinitroamino compounds (P ~ 43.4-43.7
      GPa; D ~ 9.6-9.7 km s(-1)) showed their superiority over HMX (P ~ 39.3 GPa and D
      ~ 9.10 km s(-1)). Impact sensitivity (h 50) of the designed molecules was
      compared with nitro- and nitramino-based commercial explosives on the basis of
      the available free space (?V) per molecule in their crystal lattice estimated
      using wave function analysis. The study showed that dinitroamino compounds were
      more sensitive compared to their nitro analogs. Reactivity or chemical stability
      of the designed molecules were measured in terms of charge distribution,
      molecular electrostatic potential and frontier molecular orbital energy. The
      nitro compounds of N-oxides of octaazaanthracene were found to be more stable
      than their dinitroamino analogs.

PMID- 25617210
TI  - Theoretical study of the reaction mechanism of CH3NO2 with NO2, NO and CO: the
      bimolecular reactions that cannot be ignored.
AB  - The intriguing decompositions of nitro-containing explosives have been attracting
      interest. While theoretical investigations have long been concentrated mainly on
      unimolecular decompositions, bimolecular reactions have received little
      theoretical attention. In this paper, we investigate theoretically the
      bimolecular reactions between nitromethane (CH3NO2)-the simplest nitro-containing
      explosive-and its decomposition products, such as NO2, NO and CO, that are
      abundant during the decomposition process of CH3NO2. The structures and potential
      energy surface (PES) were explored at B3LYP/6-31G(d), B3P86/6-31G(d) and MP2/6
      311 + G(d,p) levels, and energies were refined using CCSD(T)/cc-pVTZ methods.
      Quantum chemistry calculations revealed that the title reactions possess small
      barriers that can be comparable to, or smaller than, that of the initial
      decomposition reactions of CH3NO2. Considering that their reactants are abundant
      in the decomposition process of CH3NO2, we consider bimolecular reactions also to
      be of great importance, and worthy of further investigation. Moreover, our
      calculations show that NO2 can be oxidized by CH3NO2 to NO3 radical, which
      confirms the conclusion reached formerly by Irikura and Johnson [(2006) J Phys
      Chem A 110:13974-13978] that NO3 radical can be formed during the decomposition
      of nitramine explosives. 

PMID- 25617211
TI  - A single theoretical descriptor for the bond-dissociation energy of substituted
      phenols.
AB  - Relative to the corresponding value of phenol, the bond-dissociation energies
      (BDE) of substituted phenols correlate well with a single descriptor: the
      Mulliken charge on the oxygen atom of the phenoxyl radical. However, the
      correlation fails for phenols ortho-substituted with polar groups. Internal
      reaction coordinates (IRC) for the model reaction of hydrogen abstraction by the
      hydroperoxyl radical from various 2- and 4-substituted phenols were calculated in
      order to investigate the role of intra-molecular hydrogen bonds and steric
      effects on the process. Calculations yielded theoretical values in good agreement
      with experimental DeltaBDE values. The hydrogen-abstraction process was further
      analyzed in terms of density functional theory (DFT)-based reactivity indices
      such as local electrophilicity, the Fukui function for nucleophilic attack, and
      dual descriptor values of the phenolic hydroxyl oxygen along the IRC. 

PMID- 25617212
TI  - Direct and solvent-assisted keto-enol tautomerism and hydrogen-bonding
      interactions in 4-(m-chlorobenzylamino)-3-phenyl-4,5-dihydro-1H-1,2,4-triazol-5
      one: a quantum-chemical study.
AB  - The tautomeric equilibrium of the title triazole compound was computationally
      analyzed at the B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory. The
      solvent effect was considered for three solvents (chloroform, methanol, and
      water). Two distinct mechanisms were applied: a direct intramolecular transfer
      using the polarizable continuum model (PCM) and a solvent-assisted mechanism. The
      calculations indicated that the keto form is more stable in all cases. It was
      found that the barrier heights for the tautomerization reaction are very high,
      indicating a relatively disfavored process. Although the barrier heights for
      solvent-assisted reactions are significantly lower than those for the unassisted
      tautomerization reaction, implying the importance of the superior catalytic
      effect of the solvents, monosolvation was not found to be sufficient for the
      reaction to occur. Finally, the two intermolecular hydrogen-bonding interactions
      in the crystal structure were investigated in the gas phase; according to the
      calculated energies and structural parameters, the order of stability is N3
      H3...O1 > N1-H1...O1. 

PMID- 25617213
TI  - What factors influence follow-up in orthopedic trauma surgery?
AB  - BACKGROUND: Among surgical patients, follow-up visits are essential for
      monitoring post-operative recovery and determining ongoing treatment plans. Non
      adherence to clinic follow-up appointments has been associated with poorer
      outcomes in many different patient populations. We sought to identify factors
      associated with non-attendance at follow-up appointments for orthopedic trauma
      patients. MATERIALS AND METHODS: A retrospective chart review at a level I trauma
      center identified 2,165 patients who underwent orthopedic trauma surgery from
      2008 to 2009. Demographic data including age, sex, race, tobacco use, American
      Society of Anesthesiologist (ASA) score, insurance status, distance from the
      hospital, and follow-up time were collected. Injury characteristics including
      fracture type, anatomic location of the operation, length of hospital stay,
      living situation and employment status were recorded. Attendance at the first
      scheduled follow-up visit was recorded. Multivariable log-binomial regression
      analyses were used with statistical significance maintained at p < 0.05. RESULTS:
      Of the 2,165 patients included in the analysis, 1,449 (66.9 %) attended their
      first scheduled post-operative clinic visit. 33.1 % (717) were not compliant with
      keeping their first clinic appointment after surgery. Patients who used tobacco,
      lived more than 100 miles from the clinic site, did not have private insurance,
      had an ASA score >2, or had a fracture of the hip or pelvis were significantly
      less likely to follow-up. Age, sex, and race were not significantly associated
      with failure to follow-up. DISCUSSION: Follow-up appointments are essential for
      preventing complications among orthopedic trauma patients. By identifying
      patients at risk of failure to follow-up, orthopedic surgeons can appropriately
      design and implement long-term treatment plans specifically targeted for high
      risk patients.

PMID- 25617214
TI  - Monitoring and adherence in asthma management.

PMID- 25617215
TI  - The effect of an electronic monitoring device with audiovisual reminder function
      on adherence to inhaled corticosteroids and school attendance in children with
      asthma: a randomised controlled trial.
AB  - BACKGROUND: Suboptimum adherence to preventive asthma treatment is associated
      with substantial morbidity and mortality, yet adherence often remains poor. We
      aimed to investigate whether use of an inhaler with audiovisual reminders leads
      to improved adherence and asthma outcomes in school-aged children who presented
      to the emergency department with an asthma exacerbation. METHODS: We did a
      randomised controlled trial in patients aged 6-15 years who attended the regional
      emergency department in Auckland, New Zealand with an asthma exacerbation and
      were on regular inhaled corticosteroids. Using a simple, unrestricted block
      randomisation with block sizes of 200, we randomly assigned patients to receive
      an electronic monitoring device for use with their preventer inhaler with the
      audiovisual reminder functions either enabled to support adherence to inhaled
      corticosteroids (intervention group) or disabled (control group). Participants
      were followed up every 2 months for 6 months. The primary outcomes were adherence
      to preventive inhaled corticosteroids and number of days absent from school for
      any reason. Asthma control was assessed as a secondary outcome. All analyses were
      done in the intention-to-treat population. This trial is registered with the
      Australian New Zealand Clinical Trials Registry, number ACTRN12613001353785.
      FINDINGS: The study took place between May 10, 2010, and Feb 26, 2012. We
      randomly assigned 220 patients, 110 to the intervention group and 110 to the
      control group. Median percentage adherence was 84% (10th percentile 54%, 90th
      percentile 96%) in the intervention group, compared with 30% (8%, 68%) in the
      control group (p<0.0001). The proportion of days absent from school for any
      reason was 1.9% (10th percentile 0.0%, 90th percentile 7.9%) in the intervention
      group and 1.7% (0.0%, 8.6%) in the control group. The change in asthma morbidity
      score from baseline to 6 months was significantly greater in the intervention
      group than in the control group (p=0.008), with a reduction of 2.0 points from a
      mean baseline score of 9.3 (SD 2.2) to 7.3 (2.1) in the intervention group,
      compared with a reduction of 1.2 points from a baseline of 9.2 (2.5) to 8.0 (2.2)
      in the control group. INTERPRETATION: Use of an electronic monitoring device with
      an audiovisual reminder led to significant improvements in adherence to inhaled
      corticosteroids in school-aged children with asthma. This intervention could be
      beneficial for the improvement of asthma control in patients for whom poor asthma
      control is related to poor adherence. FUNDING: Health Research Council of New
      Zealand and Cure Kids.

PMID- 25617216
TI  - An assessment of 2 objective measurements of web space position.
AB  - PURPOSE: To describe 2 simple objective clinical methods of measuring the web
      position between fingers and to determine their intra-observer and inter-observer
      reliabilities. METHODS: Two observers examined the second, third, and fourth web
      spaces on both hands of 30 adult healthy volunteers. The web index measured the
      web height as a relative ratio to constant anatomical landmarks on both fingers
      subtending the web. The dorsal web index took reference from the distance between
      the metacarpophalangeal and proximal interphalangeal joints, whereas the palmar
      web index was measured in relation to the distance between the most proximal
      basal digital and proximal interphalangeal joint creases. The intraclass
      correlation coefficient was used to determine intra-observer and inter-observer
      reliability. RESULTS: Intraclass correlation coefficient values for intra
      observer and inter-observer reliability were greater than 0.80, indicating
      excellent agreement. There was no statistically significant difference between
      the dorsal or palmar measurement methods in terms of reliability. CONCLUSIONS:
      The dorsal or palmar measurement method may be reliably used in healthy adults to
      establish a web index that describes the web position. The palmar method is
      considered easier to perform. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

PMID- 25617217
TI  - Correlation of clinical disease severity to radiographic thumb osteoarthritis
      index.
AB  - PURPOSE: To determine if a slight modification of the 1987 Eaton-Glickel staging
      and interpreting 4 standardized radiographs for trapeziometacarpal (TMC)
      osteoarthritis (OA) improved analysis, to determine if a quantifiable index
      measurement from a single Robert (pronated anteroposterior) view enhanced
      reproducibility, and to examine whether improved radiographic staging correlated
      to clinically relevant disease and thus support validity. METHODS: We analyzed 4
      thumb radiographs (posteroanterior, lateral, Robert, and stress views) in 60
      consecutive subjects representing an adult population spectrum of asymptomatic to
      advanced disease. Two experienced hand surgeons (A.L.L. and A.P.C.W.), 1 chief
      resident (A.J.B.), and 1 medical student (J.M.M.) performed the analysis on each
      subject's radiographs. We analyzed all 4 radiographs for Eaton and modified Eaton
      staging and then later analyzed only the Robert view for the thumb osteoarthritis
      (ThOA) index measurement. The radiographs were randomized and reread a week later
      for each classification at separate times. Surgically excised trapeziums from
      20/60 subjects were inspected for first metacarpal surface disease and correlated
      to the 3 classifications. RESULTS: All 3 staging classifications demonstrated
      high reproducibility, with the intraclass correlation coefficient averaging 0.73
      for the Eaton, 0.83 for the modified Eaton, and 0.95 for the ThOA index.
      Articular wear and metacarpal surface eburnation correlated highest to the ThOA
      index, with advanced disease 1.55 or greater correlating to Eaton III/IV and
      modified Eaton stage 3/4 in a linear relationship. CONCLUSIONS: The ThOA index
      based on a Robert view provided a measurable alternative to Eaton staging and
      correlated to severity of surgically relevant thumb TMC OA. CLINICAL RELEVANCE: A
      simple reproducible radiographic measurement may enhance TMC OA classification
      and provide a reliable means to predict clinical disease. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Diagnostic II.

PMID- 25617218
TI  - Evaluation of expectations and expectation fulfillment in patients treated for
      trapeziometacarpal osteoarthritis.
AB  - PURPOSE: To determine the main reasons why patients with trapeziometacarpal
      osteoarthritis (TMC OA) seek treatment, their pretreatment expectations for the
      final outcome, fulfillment after one year, and predictors of fulfillment of the
      expectation. METHODS: We included 163 patients with TMC OA. They filled out
      questionnaires assessing expectations and functional status before and at 3, 6,
      and 12 months after treatment. RESULTS: Pain reduction was the most important
      reason why 65% of all patients sought treatment, whereas 17% and 13% requested
      treatment to improve hand function and activities of daily living, respectively.
      No patients considered improved appearance of the hand to be the main reason for
      undertaking treatment. Expectations before treatment were anticipated to be
      totally or mostly fulfilled by 93% of surgically treated patients and 59% of
      patients treated with corticosteroid injection. After one year, 77% of surgically
      treated patients rated their expectations as completely or mostly fulfilled,
      compared with 24% of patients treated with corticosteroid injections. Including
      all variables before treatment in a best-fit regression model, fulfillment of
      patients' expectations could not be sufficiently predicted. However, with
      addition to the model of the outcome of pain at one year, 48% of the variance of
      fulfilled expectations could be accounted for. CONCLUSIONS: Patients with TMC OA
      predominantly visit hand surgeons seeking treatment to reduce pain, whereas
      function and aesthetics have minor roles. Based on variables before treatment, no
      prediction can be made regarding whether expectations will be fulfilled after
      treatment because residual pain at one year contributes considerably to the
      variance in fulfilled expectations. Clinicians should assess patients'
      expectations before treatment and explain realistic treatment outcomes to obtain
      best treatment results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 25617220
TI  - Conservative management of elbow dislocations with an overhead motion protocol.
AB  - PURPOSE: To report the results of using an overhead motion protocol in 27
      patients and to assess final range of motion and incidence of persistent
      instability in this cohort. METHODS: A total of 27 patients were included who
      sustained a simple elbow dislocation and were treated nonsurgically with an
      overhead motion protocol designed to convert gravity from a distracting to a
      stabilizing force. Motion was initiated within 1 week of injury and average
      follow-up was 29 months. Final arc of motion and prevalence of instability were
      the primary outcomes measures. RESULTS: Final mean arc of extension to flexion
      was from 6 degrees  to 137 degrees , and of pronation to supination was from 87
      degrees  to 86 degrees . No recurrent instability was observed in this cohort and
      all patients were fully functional and without limitations at latest follow-up.
      CONCLUSIONS: The overhead motion protocol was a reliable rehabilitation program
      after elbow dislocation that allowed for controlled early motion by placing the
      elbow in an inherently stable position. Prompt initiation of motion in a
      protected position can optimize final motion and satisfaction outcomes, and when
      done in a mechanically advantageous position it can potentially limit the risk of
      recurrent instability. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25617219
TI  - Hemi-hypoglossal nerve transfer for obstetric brachial plexus palsy: report of 3
      cases.
AB  - Use of the entire hypoglossal nerve for nerve transfer in obstetric palsy is not
      recommended because of major donor nerve morbidity in terms of feeding and speech
      problems. We used a hemi-hypoglossal nerve transfer for biceps reinnervation in
      obstetric palsy in 3 infants with multiple root avulsions. Two of the 3 infants
      recovered normal or near-normal elbow flexion. There was no donor nerve morbidity
      in terms of feeding. Speech was assessed at age 20 to 27 months and was
      appropriate for age, which indicates that early speech development (speech
      intelligibility and articulation) were not affected. However, phonological
      development (expected to develop by age 3 y) and full consonant development
      (expected to be complete by age 5 y) could not be assessed because all children
      were younger than age 3 years at final follow-up. Our results confirm the
      relative safety of using a hemi-hypoglossal nerve transfer in infants. The
      transfer deserves study in a larger series and with longer follow-up,
      particularly regarding speech development. 

PMID- 25617221
TI  - Surface replacement arthroplasty of the proximal interphalangeal joint using the
      SR PIP implant: long-term results.
AB  - PURPOSE: To evaluate the long-term results of proximal interphalangeal (PIP)
      joint surface replacement arthroplasty for arthritis using the SR PIP implant
      (Small Bone Innovations, New York, NY). METHODS: This is a long-term
      retrospective analysis of results in 39 of 43 joints first reported in 2008.
      Subjective results were based upon a mailed questionnaire. Active range of motion
      was measured by a certified hand therapist, and x-rays were obtained to analyze
      changes occurring since the first study. RESULTS: The average follow-up time was
      9.3 years. The average active PIP joint arc of motion in the present cohort of
      patients went from 64 degrees  at the first report (2008) to 56 degrees  at this
      time. Radiographic comparisons revealed no major changes since the first study.
      Ten of 11 revisions were done for pain due to loosening and were performed at an
      average of 20 months after the primary procedure. No further revisions were
      necessary in the interim. Overall, subjective measures of satisfaction and
      symptomatic and functional improvement remained unchanged. CONCLUSIONS: Surface
      replacement arthroplasty using the SR PIP implant continues to be an option for
      patients with osteoarthritis of the PIP joint. Long-term subjective and objective
      outcomes are comparable to those reported using other implants. This and other
      studies suggest that this procedure is not appropriate for most rheumatoid
      joints. In the interim between studies, we saw a reduction in the average PIP
      joint arc of motion, although this change did not reach statistical significance.
      Our original revision incidence of 26% has not changed. Subjective evaluation and
      radiologic findings did not change between studies. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 25617222
TI  - Treatment of pediatric migraine.
AB  - OPINION STATEMENT: The diagnosis of migraine in the pediatric population is
      increasing as providers are becoming more familiar with recognizing the
      condition. Over-the-counter and migraine-specific treatment, once considered off
      label, have proven to be effective, especially if given at the early onset of
      head pain. Mild to severe cases of migraine should be treated with nonsteroidal
      anti-inflammatory drugs (NSAIDs), with triptans used alone or in combination in
      moderate to severe headaches unresponsive to over-the-counter therapy. Rescue
      medication including dihydroergotamine (DHE), a potent vasoconstrictor should be
      used for intractable migraines and is preferred in the hospital setting. Anti
      emetics that have anti-dopaminergic properties can be helpful in patients with
      associated symptoms of nausea and vomiting along with headache, especially when
      used in combination therapy. Preventative treatment should be initiated early in
      patients with frequent headaches to improve headache outcomes and quality of
      life. Patients and families should be educated on non-pharmacologic management,
      such as lifestyle modification and avoidance of triggers, that can prevent
      progression and worsening of migraine.

PMID- 25617224
TI  - Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma.
AB  - BACKGROUND: Low levels of vitamin D are associated with asthma severity, airway
      remodeling, and exacerbation rate increase, especially in nonatopic asthma.
      Reduced steroid responsiveness or impaired antimicrobial defense might be
      underlying mechanisms. OBJECTIVE: We sought to evaluate the effect of vitamin D
      supplementation on eosinophilic and neutrophilic airway inflammation in patients
      with nonatopic asthma. METHODS: In a double-blind, randomized, placebo-controlled
      trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on
      sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with
      neutrophilic (>=53%) and/or eosinophilic (>=3%) airway inflammation. Sputum
      induction was performed at baseline and after 9 weeks. Other measurements
      included questionnaires, blood samples, and pulmonary function. RESULTS:
      Treatment with vitamin D did not significantly affect sputum neutrophils or
      eosinophils compared with treatment with placebo in the total group. Regarding
      sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline
      sputum eosinophil levels (interaction P = .015). In patients with eosinophil
      levels of 26.2% or more (median in patients with sputum eosinophilia, >3%),
      eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment
      as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P
      = .034). Vitamin D treatment also resulted in slightly better Asthma Control
      Questionnaire scores (P = .08). CONCLUSIONS: Vitamin D supplementation reduced
      eosinophilic airway inflammation in patients with nonatopic asthma with severe
      eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a
      small effect on asthma control was observed. These findings suggest that vitamin
      D might have potential as an add-on treatment option in eosinophilic asthma.

PMID- 25617223
TI  - Persistence of asthma requires multiple feedback circuits involving type 2 innate
      lymphoid cells and IL-33.
AB  - BACKGROUND: Asthma in a mouse model spontaneously resolves after cessation of
      allergen exposure. We developed a mouse model in which asthma features persisted
      for 6 months after cessation of allergen exposure. OBJECTIVE: We sought to
      elucidate factors contributing to the persistence of asthma. METHODS: We used a
      combination of immunologic, genetic, microarray, and pharmacologic approaches to
      dissect the mechanism of asthma persistence. RESULTS: Elimination of T cells
      though antibody-mediated depletion or lethal irradiation and transplantation of
      recombination-activating gene (Rag1)(-/-) bone marrow in mice with chronic asthma
      resulted in resolution of airway inflammation but not airway hyperreactivity or
      remodeling. Elimination of T cells and type 2 innate lymphoid cells (ILC2s)
      through lethal irradiation and transplantation of Rag2(-/-)gammac(-/-) bone
      marrow or blockade of IL-33 resulted in resolution of airway inflammation and
      hyperreactivity. Persistence of asthma required multiple interconnected feedback
      and feed-forward circuits between ILC2s and epithelial cells. Epithelial IL-33
      induced ILC2s, a rich source of IL-13. The latter directly induced epithelial IL
      33, establishing a positive feedback circuit. IL-33 autoinduced, generating
      another feedback circuit. IL-13 upregulated IL-33 receptors and facilitated IL-33
      autoinduction, thus establishing a feed-forward circuit. Elimination of any
      component of these circuits resulted in resolution of chronic asthma. In
      agreement with the foregoing, IL-33 and ILC2 levels were increased in the airways
      of asthmatic patients. IL-33 levels correlated with disease severity.
      CONCLUSIONS: We present a critical network of feedback and feed-forward
      interactions between epithelial cells and ILC2s involved in maintaining chronic
      asthma. Although T cells contributed to the severity of chronic asthma, they were
      redundant in maintaining airway hyperreactivity and remodeling.

PMID- 25617225
TI  - Exosome secretion by eosinophils: A possible role in asthma pathogenesis.
AB  - BACKGROUND: Eosinophils secrete several granules that are involved in the
      propagation of inflammatory responses in patients with pathologies such as
      asthma. OBJECTIVE: We hypothesized that some of these granules are exosomes,
      which, when transferred to the recipient cells, could modulate asthma
      progression. METHODS: Eosinophils were purified from peripheral blood and
      cultured with or without IFN-gamma or eotaxin. Multivesicular bodies (MVBs) in
      eosinophils were studied by using fluorescence microscopy, transmission electron
      microscopy (TEM), and flow cytometry. Exosome secretion was measured and exosome
      characterization was performed with TEM, Western blotting, and NanoSight
      analysis. RESULTS: Generation of MVBs in eosinophils was confirmed by using
      fluorescence microscopy and flow cytometry and corroborated by means of TEM.
      Having established that eosinophils contain MVBs, our aim was to demonstrate that
      eosinophils secrete exosomes. To do this, we purified exosomes from culture
      medium of eosinophils and characterized them. Using Western blot analysis, we
      demonstrated that eosinophils secreted exosomes and that the discharge of
      exosomes to extracellular media increases after IFN-gamma stimulation. We
      measured exosome size and quantified exosome production from healthy and
      asthmatic subjects using nanotracking analysis. We found that exosome production
      was augmented in asthmatic patients. CONCLUSION: Our findings are the first to
      demonstrate that eosinophils contain functional MVBs and secrete exosomes and
      that their secretion is increased in asthmatic patients. Thus exosomes might play
      an important role in the progression of asthma and eventually be considered a
      biomarker.

PMID- 25617227
TI  - Two-dimensional speckle-tracking-derived segmental peak systolic longitudinal
      strain identifies regional myocardial involvement in patients with myocarditis
      and normal global left ventricular systolic function.
AB  - The presence of myocardial late gadolinium enhancement (LGE) by cardiac magnetic
      resonance (CMR) imaging in concert with electrocardiography and elevated
      biomarkers helps support the diagnosis of acute myocarditis. Two-dimensional
      echocardiography is limited to global and qualitative regional function
      assessment and may not contribute to the diagnosis, especially in the presence of
      normal LV systolic function. Two-dimensional speckle-tracking (2D-STE)-derived
      segmental peak systolic (pkS) longitudinal strain (LS) may identify segmental
      myocardial involvement in myocarditis. We sought to identify an association
      between segmental pkS, LGE, and troponin levels in patients with myocarditis.
      Retrospective analysis of myocardial segmental function by 2D-STE segmental
      strain was compared to the presence of LGE and admission peak troponin levels in
      patients with acute myocarditis and preserved global LV systolic function.
      American Heart Association 17-segment model was used for comparison between
      imaging modalities. Global function was assessed by m-mode-derived shortening
      fraction (SF). Descriptive statistics and regression analysis were utilized.
      Forty-four CMRs performed to evaluate for myocarditis were identified. Of the 44,
      10 patients, median age 17.5 years (14-18.5 years) and median SF 35 % (28-44 %),
      had paired CMR and 2D-STE data for analysis, and 161/170 segments could be
      analyzed by both methods for comparison. PkS LS was decreased in 51 % of segments
      that were positive for LGE with average pkS of -14.7 %. Segmental pkS LS
      abnormalities were present in all but one patient who had abnormal pkS
      circumferential strain. Global pkS LS was decreased in patients with myocarditis.
      There is a moderate correlation between decreased pkS LS and the presence of LGE
      by CMR, 2D-STE for myocardial involvement in acute myocarditis can serve as an
      useful noninvasive adjunct to the existing tests used for the diagnosis of acute
      myocarditis and might have a role in prognostication.

PMID- 25617226
TI  - Neighborhood poverty, urban residence, race/ethnicity, and asthma: Rethinking the
      inner-city asthma epidemic.
AB  - BACKGROUND: Although it is thought that inner-city areas have a high burden of
      asthma, the prevalence of asthma in inner cities across the United States is not
      known. OBJECTIVE: We sought to estimate the prevalence of current asthma in US
      children living in inner-city and non-inner-city areas and to examine whether
      urban residence, poverty, or race/ethnicity are the main drivers of asthma
      disparities. METHODS: The National Health Interview Survey 2009-2011 was linked
      by census tract to data from the US Census and the National Center for Health
      Statistics. Multivariate logistic regression models adjusted for sex; age;
      race/ethnicity; residence in an urban, suburban, medium metro, or small
      metro/rural area; poverty; and birth outside the United States, with current
      asthma and asthma morbidity as outcome variables. Inner-city areas were defined
      as urban areas with 20% or more of households at below the poverty line. RESULTS:
      We included 23,065 children living in 5,853 census tracts. The prevalence of
      current asthma was 12.9% in inner-city and 10.6% in non-inner-city areas, but
      this difference was not significant after adjusting for race/ethnicity, region,
      age, and sex. In fully adjusted models black race, Puerto Rican ethnicity, and
      lower household income but not residence in poor or urban areas were independent
      risk factors for current asthma. Household poverty increased the risk of asthma
      among non-Hispanics and Puerto Ricans but not among other Hispanics. Associations
      with asthma morbidity were very similar to those with prevalent asthma.
      CONCLUSIONS: Although the prevalence of asthma is high in some inner-city areas,
      this is largely explained by demographic factors and not by living in an urban
      neighborhood.

PMID- 25617229
TI  - Outcomes of open repair for chronic descending thoracic aortic dissection.
AB  - BACKGROUND: This study analyzed early and late outcomes after open repair of
      descending thoracic aortic aneurysms with chronic aortic dissection. METHODS: We
      retrospectively reviewed our cases of open repair of descending thoracic aortic
      aneurysms with chronic dissection from 1991 to 2011. Patient comorbid conditions
      and operative details were analyzed to determine risks for adverse outcome. Long
      term survival and aortic reinterventions were analyzed. RESULTS: We repaired 519
      patients with descending thoracic aortic aneurysms during the study period, and
      209 (40%) had chronic dissection. Mean age was 59 years, with 74% (154 of 209)
      men. Previous ascending repair was performed in 41% (85 of 209), and the second
      stage elephant trunk was performed in 10% (21 of 209). Adjunctive distal aortic
      perfusion with cerebral spinal fluid drainage was used in 90% (188 of 209) of
      patients, and circulatory arrest with bypass in 1% (3 of 209). The 30-day
      mortality was 8.6% (18 of 209). Immediate neurologic deficit occurred in 0.95% (2
      of 209) and only with extent C resection. Delayed neurologic deficit occurred in
      1.4% (3 of 209), 1 patient in each extent. Because 66% (2 of 3) of the patients
      with delayed neurologic deficit recovered function, permanent deficit occurred in
      1.4% (3 of 209). Stroke occurred in 2.4% (5 of 209) and dialysis on discharge in
      5% (11 of 211). The only risk factor for 30-day mortality was preoperative
      glomerular filtration rate of less than 60 mL/min (odds ratio, 4.2; p < 0.006).
      Survival at 5, 10, and 15 years was 72%, 60%, and 49%, respectively. Freedom from
      reoperation on the operated-on segment was 98%, 96.5%, 96.5%, and 96.5% at 5, 10,
      15, and 20 years. CONCLUSIONS: Open repairs of chronic descending thoracic aortic
      aneurysm dissections can be performed with respectable morbidity and mortality.
      Neurologic deficit remains low with the use of adjuncts, and early deaths are
      directly related to preoperative renal status. Reintervention on the involved
      aortic segment is low. These results allow comparisons with endovascular repair
      for chronic aortic dissection.

PMID- 25617230
TI  - Creating creationists: The influence of 'issues framing' on our understanding of
      public perceptions of clash narratives between evolutionary science and belief.
AB  - Clash narratives relating to evolutionary science and personal belief are a
      recurrent theme in media or public space discourse. However, a 2009 British
      Council poll undertaken in 10 countries worldwide shows that the perception of a
      necessary clash between evolutionary worldviews and belief in a God is a minority
      viewpoint. How then does the popular conception that there is an ongoing conflict
      between evolution and belief in God arise? One contributing factor is the framing
      and categorization of creationism and evolutionism within large-scale surveys for
      use within media campaigns. This article examines the issue framing within four
      polls conducted in the United Kingdom and internationally between 2008 and 2013.
      It argues that by ignoring the complexity and range of perspectives individuals
      hold, or by framing evolutionary science as atheistic, we are potentially
      creating 'creationists' - including 'Islamic creationists' - both figuratively
      and literally. 

PMID- 25617228
TI  - Pulmonary valve replacement: twenty-six years of experience with mechanical
      valvar prostheses.
AB  - BACKGROUND: Although the thromboembolic risk after pulmonary valve replacement
      (PVR) with mechanical valves is presumed to be high, recent studies suggest
      promising short-term and mid-term results. However, large studies reporting long
      term mortality and valve-related complications are missing. METHODS: We describe
      valve-related complications in 66 patients with a mechanical pulmonary valvar
      prosthesis implanted between 1987 and 2013. RESULTS: Mean follow-up duration was
      5.9 +/- 4.8 years (median 4.9). Mean age at time of implantation was 35 +/- 13
      years. The most frequent underlying cardiac diagnosis was tetralogy of Fallot
      (77%). Valvar thrombosis or pannus was reported in 7 patients (10%) of which 4 in
      the setting of inadequate anticoagulation or pregnancy. Redo PVR was performed in
      6 patients. Freedom from redo PVR in survivors after 5 and 10 years was 96% and
      89%, respectively. Survival after 5 and 10 years was 91% and 81%, respectively.
      Main cause of death was end-stage heart failure. CONCLUSIONS: Success of PVR
      using mechanical valvar prostheses over 26 years was limited because of valvar
      thrombosis (often in the setting of pregnancy or incompliance with
      anticoagulation therapy) or pannus. Performance of mechanical prostheses in the
      pulmonary position may improve when valvar thrombosis is prevented by patient
      selection, avoiding mechanical valves in patients at increased risk of valvar
      thrombosis, and by strict compliance to anticoagulation therapy.

PMID- 25617231
TI  - Letter to the editor.

PMID- 25617232
TI  - Serum zinc levels of cord blood: relation to birth weight and gestational period.
AB  - BACKGROUND: Zn-deficiency has been associated with numerous alterations during
      pregnancy including low birth weight; however, the research relating neonatal
      zinc status and birth weight has not produced reliable results. OBJECTIVE: To
      compare the serum Zn-levels of cord blood in healthy newborns and low birth
      weight newborns, and to assess a possible relationship between zinc concentration
      and neonatal birth weight and gestational age. MATERIAL AND METHODS: 123 newborns
      divided in "study group" (n=50) with <2500g birth weight neonates and "control
      group" (n=73) with >=2500g birth weight neonates were enrolled. Study group was
      subdivided according to gestational age in preterm (<37 weeks) and full-term
      (>=37 weeks). Serum cord blood samples were collected and the Zn-levels were
      analyzed using flame Atomic Absorption Spectrophotometry method and the result
      was expressed in MUmol/L. The Zn-levels were compared between the groups (Mann
      Whitney-U test) and the Zn-levels were correlated with the birth weight and
      gestational age (Spearman's rank correlations). RESULTS: Statistically
      significant low positive correlation between Zn-levels and birth weight
      (rho=0.283; p=0.005) was found. No statistically significant difference between
      Zn-levels of study and control groups [17.00+/-0.43 vs. 18.16+/-0.32 (p=0.053)]
      was found. Statistically significant low positive correlation between Zn-levels
      and gestational age (rho=0.351; p=0.001) was found. No statistically significant
      difference between Zn-levels of preterm as compare to full-term newborns [16.33+/
      0.42 vs. 18.43+/-0.93 (p=0.079)] was found. Zn-level of preterm subgroup was
      significantly lower compared to control group (p=0.001). CONCLUSIONS: Despite low
      birth weight preterm neonates had significantly lower serum zinc levels of cord
      blood than healthy term neonates, the correlation between cord blood zinc levels
      and birth weight and gestational age was lower. The results are not enough to
      relate the change in cord blood zinc concentration to the birth weight values or
      gestational period. In relation to complicated pregnancies, further studies
      regarding zinc levels in blood in our population are required.

PMID- 25617233
TI  - Brain most susceptible to cadmium induced oxidative stress in mice.
AB  - Accumulated evidence over the years indicate that cadmium (Cd) may be a possible
      etiological factor for neurodegenerative diseases. This may possibly be linked to
      excessive generation of free radicals that damages the organs in the body
      depending on their defence mechanism. Since Cd is a toxic agent that affect
      several cell types, the aim of this study was to shed light on the effect of Cd
      and its consequences on different organs of the mice body. To test the hypothesis
      of concentration dependent Reactive Oxygen Species (ROS) generation and DNA
      damage, observations were done in the serum of 4-5 weeks old male Swiss albino
      mice by treating with cadmium chloride (CdCl2) in drinking water for 30 days. The
      expression of Bcl-2-associated X protein (Bax) an apoptotic marker protein was
      two times higher in brain compared to liver at an exposure level of 0.5mgL(-1)
      CdCl2. Furthermore the correlation and linkage data analysis of antioxidant
      defence system revealed a rapid alteration in the brain, compared to any other
      organs considered in this study. We report that even at low dose of Cd, it
      impaired the brain due to lipid peroxidase sensitivity which favoured the Cd
      induced oxidative injury in the brain. 

PMID- 25617234
TI  - Meta-analysis of defunctioning stoma in low anterior resection with total
      mesorectal excision for rectal cancer: evidence based on thirteen studies.
AB  - BACKGROUND: Recent studies have shown that a protective stoma can reduce
      morbidity in low anterior resection for rectal cancer; however, the necessity of
      it is still controversially discussed. METHODS: We performed this meta-analysis
      to provide a comprehensive evaluation of the role of defunctioning stoma in low
      anterior resection for rectal cancer on the rates of anastomotic leakage and
      reoperation related to leakage with or without defunctioning stoma by calculating
      the pooled risk ratio. RESULTS: Studies and relevant literature published between
      2004 and 2014 regarding the construction of a protective stoma after low anterior
      resection were searched though PubMed and EMBASE databases. Finally, a total of
      13 studies including 8,002 patients were included in this meta-analysis. The
      results indicated that protective stomas significantly reduced the rate of
      postoperative anastomotic leakage and reoperation after low anterior rectal
      resection. The pooled risk ratios were 0.47 (95% CI: 0.33-0.68, P <0.0001) and
      0.36 (95% CI: 028-0.46, P <0.00001), respectively. CONCLUSIONS: The findings from
      this present meta-analysis suggest that a defunctioning stoma could effectively
      reduce the clinical consequences of anastomotic leakage and reoperation, it is
      recommended in patients undergoing low rectal anterior resection for rectal
      cancer.

PMID- 25617235
TI  - Validation of the neutrophil-to-lymphocyte ratio as a prognostic factor in a
      cohort of European prostate cancer patients.
AB  - PURPOSE: Recent studies have expanded the concept that the systemic inflammatory
      response has an important role in the progression of several solid tumors. The
      neutrophil-to-lymphocyte ratio (NLR), an easily determinable marker of systemic
      inflammation, has been associated with clinical outcome in various cancer
      entities. In the present study, we validated the prognostic relevance of an
      elevated NLR in a cohort of European prostate cancer patients. METHODS: Data from
      415 consecutive prostate cancer patients treated with 3D conformal radiotherapy
      at a single tertiary academic center from 1999 to 2007 were included in this
      retrospective study. Clinical progression-free survival (PFS), distant metastases
      free survival (DMFS), and overall survival (OS) were assessed using the Kaplan
      Meier method. To evaluate the prognostic relevance, univariate and multivariate
      Cox regression models were performed for each end point. RESULTS: Based on
      previously published studies, an NLR >= 5 was selected as cutoff value for
      external validation. Multivariate analysis identified an increased NLR as an
      independent prognostic factor for clinical PFS [hazard ratio (HR) 3.09, 95 % CI
      1.64-5.82, p < 0.001], DMFS (HR 3.51, 95 % CI 1.80-6.85, p < 0.001), and OS (HR
      2.16, 95 % CI 1.17-3.99, p = 0.013). CONCLUSION: The NLR seems to represent an
      independent prognostic marker and should be considered for future individual risk
      assessment in patients with prostate cancer.

PMID- 25617236
TI  - Hand-assisted laparoscopic bladder cuff excision via the same hand port as that
      used for nephroureterectomy.
AB  - PURPOSE: The aim of this study was to report our technique of hand-assisted
      laparoscopic bladder cuff excision through the same hand port as that used for
      nephroureterectomy and evaluate its benefits and short-term oncologic outcomes.
      MATERIALS AND METHODS: We included 67 consecutive patients treated by a single
      surgeon between June 2011 and November 2014 with hand-assisted laparoscopic
      bladder cuff excision through the same hand port as that used for
      nephroureterectomy. We retrospectively analyzed procedure-related clinical data
      and short-term oncologic outcomes. RESULTS: The mean patient age was 66.2 +/-
      10.6 years. The mean follow-up period was 17.6 months (range 1-37 months). The
      mean operation time was 243.5 +/- 60.4 min. There were no major accidents or open
      conversions. Forty-two patients (63 %) underwent immediate mitomycin C
      instillation without complications. There was one high-grade complication
      (prolonged lymphatic leakage) that required reoperation and multiple
      hospitalizations. Thirty patients (45 %) underwent regional lymph node
      dissection. The pathological stages included CIS in 2 (3 %), Ta/T1 in 32 (48 %),
      T2 in 6 (9 %), T3 in 27 (40 %), and N+ in 4 (6 %) cases. G1, G2, and G3 were seen
      in 3 (5 %), 21 (31 %), and 43 (64 %) patients, respectively. Eighteen patients
      (26 %) underwent postoperative adjuvant chemotherapy. Two patients died during
      the study period, and nine patients (13 %) had bladder recurrences. CONCLUSIONS:
      HAL bladder cuff excision through the same hand port used for nephroureterectomy
      is a feasible technique that is both amenable to oncologic principles and can
      reproduce the open surgical technique.

PMID- 25617237
TI  - Effect of topical application of quercetin-3-O-(2"-gallate)-alpha-l
      rhamnopyranoside on atopic dermatitis in NC/Nga mice.
AB  - BACKGROUND: Quercetin-3-O-(2"-gallate)-alpha-l-rhamnopyranoside (QGR) is a new
      quercetin derivative which is isolated from the leaves of Acer ginnala Maxim, a
      native plant of Korea. Quercetin has several biological effects including
      antioxidative, anti-inflammatory, and anti-allergic effects. However, the topical
      effect of QGR on atopic dermatitis (AD) like skin lesion in NC/Nga mice has not
      been studied. OBJECTIVE: To evaluate the anti-inflammatory and anti-allergic
      effect of QGR in a murine model of atopic dermatitis. METHODS: We measured
      inducible nitric oxide synthase (iNOS) and cyclooxygenase -2(COX-2) level in
      RAW264.7 cell with QGR treatment. And after induction of AD like skin lesions
      with Dermatophagoides farina (Df) ointment, mice were treated with QGR and
      control drugs. Clinical scores, interleukin (IL) 4, 5, and 13, serum IgE,
      eosinophil levels, iNOS and COX-2 level were evaluated. RESULTS: Results show
      that mRNA level of iNOS and COX-2 in vitro were decreased after QGR treatment.
      Topical QGR markedly decreased the iNOS and COX-2 mRNA expressions in the skin.
      QGR also significantly suppressed the increase in the level of total plasma IgE
      and eosinophils. In addition, topical application of QGR down-regulated the
      expressions of the cytokines, IL-4,5 and 13, which were induced by Df ointment
      stimulation. CONCLUSIONS: In the present study, we showed that topical
      application of QGR ameliorated Df-induced AD-like inflammatory responses in
      NC/Nga mice. These results demonstrate that QGR might be beneficial in the
      treatment of AD.

PMID- 25617238
TI  - The ginsenosides of Panax ginseng promote hair growth via similar mechanism of
      minoxidil.

PMID- 25617239
TI  - Pneumoscrotum after tracheal intubation.
AB  - Air in the scrotum is an unusual clinical finding and a thorough search should be
      done in order to locate the air leak or source of gas production. We report an 81
      year-old patient who developed severe acute respiratory failure after fiberoptic
      bronchoscopy and was intubated immediately. After tracheal intubation, excessive
      subcutaneous emphysema from the head to the scrotum was obvious. Chest tube
      thoracostomies were placed to treat pneumothorax. The emphysema was absorbed
      after 13 days without any sequela. Air or gas inside the scrotum may originate
      from intraperitoneal, extraperitoneal, or local sources. The majority of the
      cases can be managed conservatively, but emergent intervention is needed in life
      threatening situations. 

PMID- 25617240
TI  - Commentary on: "Impact of the European Working Time Directive (EWTD) on the
      operative experience of surgical residents".

PMID- 25617241
TI  - Regarding "worse outcomes among uninsured general surgery patients: does the need
      for an emergency operation explain these disparities?".

PMID- 25617242
TI  - Use and misuse of glucocorticoids in the community of Raxaul Block, North Bihar.
AB  - BACKGROUND: Glucocorticoid misuse is widely recognised but inadequately addressed
      issue in India. This study reports the use and misuse of glucocorticoids in
      Raxaul Block, North Bihar, India. METHODS: A two-stage sampling method was used
      to interview 240 households during April and May 2013. In each household, anyone
      who had been sick in the last 6 months had their medication use recorded.
      RESULTS: In total, 113 out of 334 (33.8%) were found to have taken a
      glucocorticoid in the last 6 months (95% CI: 28.7-38.9%). One hundred (88.4%) of
      these were considered to be inappropriate. Seventy-nine percent had been using
      glucocorticoids for more than 1 month; 60.2% were prescribed by local, unlicensed
      practitioners. CONCLUSIONS: Glucocorticoid misuse will contribute to the burden
      of hypertension, diabetes, osteoporotic fracture, tuberculosis, cataracts and
      deaths due to hypoadrenal crisis. One in 15 people in Raxaul Block are likely to
      have a suppressed hypothalamo-pituitary-adrenal axis.

PMID- 25617243
TI  - Are the obstruction sites visualized on drug-induced sleep endoscopy reliable?
AB  - PURPOSE: Drug-induced sleep endoscopy (DISE) has been claimed to be a reliable
      tool, improving surgical results in obstructive sleep apnea syndrome (OSAS). One
      means of assessing reliability would be to ablate only a part of the sites
      observed on endoscopy and find only partial success versus ablating all observed
      sites and finding resolution of apnea. METHODS: A retrospective study included 24
      OSAS patients, operated on following awake clinical examination. DISE was
      performed prior to surgery. Overnight sleep study was performed before and after
      surgery. Two groups of patients were obtained: success (postoperative apnea
      hypopnea index (AHI) <10 and >50 % reduction in preoperative AHI) and failure.
      Obstruction sites found on DISE and those ablated or left after surgery were
      compared between the two groups. RESULTS: Mean AHI fell from 30.9 +/- 12.4/h to
      13.7 +/- 14.2/h after surgery. In eight of the 14 patients in the success group,
      DISE showed an obstruction site not treated by surgery. In six patients out of
      the ten patients in the failure group, all DISE sites were treated by surgery,
      which nevertheless was not effective. Four patients had retrovelar concentric
      obstruction. CONCLUSION: DISE could in some cases explain surgical failure.
      However, it also seems to show additional obstruction sites which do not need to
      be treated. Proper knowledge of pharyngeal fluid dynamics and mastery of the DISE
      technique would probably help us understand better some of the DISE findings.

PMID- 25617244
TI  - Cholesteryl ester-transfer protein inhibitors stimulate aldosterone biosynthesis
      in adipocytes through Nox-dependent processes.
AB  - Hyperaldosteronism and hypertension were unexpected side effects observed in
      trials of torcetrapib, a cholesteryl ester-transfer protein (CETP) inhibitor that
      increases high-density lipoprotein. Given that CETP inhibitors are lipid soluble,
      accumulate in adipose tissue, and have binding sites for proteins involved in
      adipogenesis, and that adipocytes are a source of aldosterone, we questioned
      whether CETP inhibitors (torcetrapib, dalcetrapib, and anacetrapib) influence
      aldosterone production by adipocytes. Studies were performed using human
      adipocytes (SW872), which express CETP, and mouse adipocytes (3T3-L1), which lack
      the CETP gene. Torcetrapib, dalcetrapib, and anacetrapib increased expression of
      CYP11B2, CYP11B1, and steroidogenic acute regulatory protein, enzymes involved in
      mineralocorticoid and glucocorticoid generation. These effects were associated
      with increased reactive oxygen species formation. Torcetrapib, dalcetrapib, and
      anacetrapib upregulated signal transducer and activator of transcription 3
      (STAT3) and peroxisome proliferation-activated receptor-gamma, important in
      adipogenesis, but only torcetrapib stimulated production of chemerin, a
      proinflammatory adipokine. To determine mechanisms whereby CETP inhibitors
      mediate effects, cells were pretreated with inhibitors of Nox1/Nox4 [GKT137831; 2
      (2-chlorophenyl)-4-[3-(dimethylamino)phenyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine
      3,6(2H,5H)-dione], Nox1 (ML171 [2-acetylphenothiazine]), mitochondria (rotenone),
      and STAT3 (S3I-201 [2-hydroxy-4-(((4-methylphenyl)sulfonyloxy)acetyl)amino)
      benzoic acid]). In torcetrapib-stimulated cells, Nox inhibitors, rotenone, and
      S3I-201 downregulated CYP11B2 and steroidogenic acute regulatory protein and
      reduced aldosterone. Dalcetrapib and anacetrapib effects on aldosterone were
      variably blocked by GKT137831, ML171, rotenone, and S3I-201. In adipocytes,
      torcetrapib, dalcetrapib, and anacetrapib inhibit enzymatic pathways responsible
      for aldosterone production through Nox1/Nox4- and mitochondrial-generated
      reactive oxygen species and STAT3. CETP inhibitors also influence adipokine
      production. These processes may be CETP independent. Our findings identify novel
      adipocyte-related mechanisms whereby CETP inhibitors increase aldosterone
      production. Such phenomena may contribute to hyperaldosteronism observed in CETP
      inhibitor clinical trials. 

PMID- 25617245
TI  - Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium
      induced activation is specific for the transporter in primates.
AB  - NaCT (SLC13A5) is a Na(+)-coupled transporter for Krebs cycle intermediates and
      is expressed predominantly in the liver. Human NaCT is relatively specific for
      citrate compared with other Krebs cycle intermediates. The transport activity of
      human NaCT is stimulated by Li(+), whereas that of rat NaCT is inhibited by
      Li(+). We studied the influence of Li(+) on NaCTs cloned from eight different
      species. Li(+) stimulated the activity of only NaCTs from primates (human,
      chimpanzee, and monkey); by contrast, NaCTs from nonprimate species (mouse, rat,
      dog, and zebrafish) were inhibited by Li(+). Caenorhabditis elegans NaCT was not
      affected by Li(+). With human NaCT, the Li(+)-induced increase in transport
      activity was associated with the conversion of the transporter from a low
      affinity/high-capacity type to a high-affinity/low-capacity type. H(+) was able
      to substitute for Li(+) in eliciting the stimulatory effect. The amino acid
      Phe500 in human NaCT was critical for Li(+)/H(+)-induced stimulation. Mutation of
      this amino acid to tryptophan (F500W) markedly increased the basal transport
      activity of human NaCT in the absence of Li(+), but the ability of Li(+) to
      stimulate the transporter was almost completely lost with this mutant.
      Substitution of Phe500 with tryptophan in human NaCT converted the transporter
      from a low-affinity/high-capacity type to a high-affinity/low-capacity type, an
      effect similar to that of Li(+) on the wild-type NaCT. These studies show that
      Li(+)-induced activation of NaCT is specific for the transporter in primates and
      that the region surrounding Phe500 in primate NaCTs is important for the Li(+)
      effect. 

PMID- 25617246
TI  - Here/In this issue and there/abstract thinking: trials in child psychiatry: and
      now ... be more pragmatic, please!

PMID- 25617247
TI  - Accountable care organizations and child and adolescent psychiatry.

PMID- 25617248
TI  - Preventive intervention efficacy, development, and neural plasticity.

PMID- 25617249
TI  - The prevalence of mental illness in homeless children: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: The numbers of children experiencing homelessness have increased. To
      develop responsive interventions, we must understand their mental
      health/behavioral needs. The purpose of this systematic review was to update the
      evidence base by identifying, appraising, and summarizing studies on the
      prevalence of mental health issues among homeless children, comparing these
      individuals to low-income-housed children, and discussing research, practice, and
      policy implications. METHOD: We searched 3 electronic databases and included
      empirical studies investigating the prevalence of mental illness in homeless
      children in the United States (1990-2014). Retrieved publications were screened,
      data extracted, and study quality appraised by independent reviewers. Evidence
      synthesis was based on qualitative and quantitative analyses. Prevalence odds
      ratios (OR) of individual studies were pooled using an inverse-variance random
      effects model. RESULTS: Twelve studies were included and reviewed. Overall, 10%
      to 26% of homeless preschoolers had mental health problems requiring clinical
      evaluation. This proportion increased to 24% to 40% among homeless school-age
      children, a rate 2 to 4 times higher than poor children aged 6 to 11 years in the
      National Survey of America's Families. According to our meta-analyses, the
      difference in prevalence measured by Child Behavior Checklist (CBCL) Total
      Problems (T score >=60-64) was not significantly different between homeless and
      housed preschool children (OR = 1.49; 95% CI = 0.97-2.28). School-age homeless
      children compared to housed children were significantly more likely to have a
      mental health problem as defined by the CBCL Total Problems subscale (T score
      >=60; OR = 1.78; 95% CI = 1.19-2.66). CONCLUSION: Evidence-based mental health
      interventions for children experiencing homelessness are long overdue. Universal
      screening, treatment plan development, and support of adaptive systems that focus
      on positive parenting and children's self-regulation are essential.

PMID- 25617250
TI  - Therapeutic interventions for suicide attempts and self-harm in adolescents:
      systematic review and meta-analysis.
AB  - OBJECTIVE: Suicidal behavior and self-harm are common in adolescents and are
      associated with elevated psychopathology, risk of suicide, and demand for
      clinical services. Despite recent advances in the understanding and treatment of
      self-harm and links between self-harm and suicide and risk of suicide attempt,
      progress in reducing suicide death rates has been elusive, with no substantive
      reduction in suicide death rates over the past 60 years. Extending prior reviews
      of the literature on treatments for suicidal behavior and repetitive self-harm in
      youth, this article provides a meta-analysis of randomized controlled trials
      (RCTs) reporting efficacy of specific pharmacological, social, or psychological
      therapeutic interventions (TIs) in reducing both suicidal and nonsuicidal self
      harm in adolescents. METHOD: Data sources were identified by searching the
      Cochrane, Medline, PsychINFO, EMBASE, and PubMed databases as of May 2014. RCTs
      comparing specific therapeutic interventions versus treatment as usual (TAU) or
      placebo in adolescents (through age 18 years) with self-harm were included.
      RESULTS: Nineteen RCTs including 2,176 youth were analyzed. TIs included
      psychological and social interventions and no pharmacological interventions. The
      proportion of the adolescents who self-harmed over the follow-up period was lower
      in the intervention groups (28%) than in controls (33%) (test for overall effect
      z = 2.31; p = .02). TIs with the largest effect sizes were dialectical behavior
      therapy (DBT), cognitive-behavioral therapy (CBT), and mentalization-based
      therapy (MBT). There were no independent replications of efficacy of any TI. The
      pooled risk difference between TIs and TAU for suicide attempts and nonsuicidal
      self-harm considered separately was not statistically significant. CONCLUSION:
      TIs to prevent self-harm appear to be effective. Independent replication of the
      results achieved by DBT, MBT, and CBT is a research priority.

PMID- 25617251
TI  - Social communication difficulties and autism in previously institutionalized
      children.
AB  - OBJECTIVE: To determine the risk of difficulties with social communication and
      restricted/repetitive behaviors as well as the rate of autism in children
      institutionalized in early infancy and to assess the impact of a foster care
      intervention on ameliorating this risk. METHOD: Children abandoned at birth and
      raised in institutions in Bucharest, Romania were randomly assigned to a care-as
      usual group (institutional care, CAUG), or placed in family-centered foster care
      (FCG) as part of the Bucharest Early Intervention Project (BEIP). At
      approximately 10 years of age, the Social Communication Questionnaire (SCQ) was
      administered to caregivers of children in both groups as well as to parents of a
      typically developing community sample (Never-Institutionalized group [NIG])
      residing in Bucharest, Romania. Children scoring >=12 on the SCQ underwent
      clinical evaluation for autism spectrum disorder (ASD). RESULTS: Caregivers of
      children with a history of institutionalization reported that these children had
      significantly more deviant behavior than never-institutionalized children on all
      subdomains of the SCQ (all p < 0.001). Children in the FCG had significantly
      lower scores on the SCQ than children in the CAUG (p < .001), particularly in the
      reciprocal social interaction domain, indicating that the intervention reduced
      problems in social communication. Three of 60 CAUG children, 2 of 57 FCG
      children, and none of the NIG children received a formal ASD diagnosis.
      CONCLUSION: Early institutional rearing was associated with an increased risk of
      social communication difficulties and ASD. A family-centered foster care
      intervention improved social communication skills.

PMID- 25617252
TI  - Treatment moderators of child- and family-focused cognitive-behavioral therapy
      for pediatric bipolar disorder.
AB  - OBJECTIVE: Prior work has demonstrated the efficacy of child- and family-focused
      cognitive-behavioral therapy (CFF-CBT) versus enhanced treatment as usual (TAU;
      unstructured psychotherapy) for pediatric bipolar disorder (PBD). The current
      study builds on primary findings by examining baseline child, parent, and family
      characteristics as moderators of symptom response trajectories. METHOD: A total
      of 69 youth aged 7 to 13 years (mean = 9.19 years, SD = 1.61 years) with DSM-IV
      TR bipolar I, II, or not otherwise specified (NOS) were randomly assigned, with
      family members, to CFF-CBT or TAU. Both treatments consisted of 12 weekly
      sessions and 6 monthly booster sessions. Participants were assessed at baseline,
      4, 8, and 12 weeks, and 6-month follow-up on mania and depression symptoms and
      overall psychiatric severity. Parents and youth also provided self-report data on
      baseline characteristics. RESULTS: CFF-CBT demonstrated greater efficacy for
      youth depressive symptoms relative to TAU for parents with higher baseline
      depressive symptoms and lower income, and marginally for families with higher
      cohesion. In addition, youth with lower baseline depression and youth with higher
      self-esteem showed a poorer response to TAU versus CFF-CBT on mania symptom
      outcomes. Age, sex, baseline mania symptoms, comorbidity, and suicidality did not
      moderate treatment response. CONCLUSION: Results indicate that CFF-CBT was
      relatively immune to the presence of treatment moderators. Findings suggest the
      need for specialized treatment to address symptoms of PBD in the context of
      parental symptomatology and financial stress.

PMID- 25617253
TI  - Efficacy and safety of paliperidone extended release in adolescents with
      schizophrenia: a randomized, double-blind study.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and tolerability of paliperidone
      extended release (ER) relative to aripiprazole in adolescent schizophrenia.
      METHOD: In this multicenter, double-blind, phase 3 study (screening [<=3 weeks],
      with an acute treatment period [8 weeks] and a maintenance period [18 weeks]),
      adolescents (12-17 years old) with schizophrenia (DSM-IV diagnosis; Positive and
      Negative Symptom Score [PANSS] total score 60-120) were randomized (1:1) to once
      daily paliperidone ER (6 mg per day [days 1-7], flexibly dosed 3, 6, or 9 mg per
      day from week 2 to end of study [EOS]), or to aripiprazole (2 mg per day [days 1
      and 2], 5 mg per day [days 3 and 4], 10 mg per day [days 5-7], flexibly dosed 5,
      10, or 15 mg per day [week 2 to EOS]). RESULTS: Overall, 76% of enrolled patients
      (174/228) completed the study (paliperidone ER, 75% [85/113]; aripiprazole, 77%
      [89/115]). There was no significant difference in change in PANSS total scores
      from baseline to day 56 (primary endpoint) (paliperidone ER versus aripiprazole, 
      19.3 [13.80] versus -19.8 [14.56], p = .935); responders, 67.9% versus 76.3%, p =
      .119) and day 182 (-25.6 [16.88] versus -26.8 [18.82], p = .877; responders,
      76.8% versus 81.6%, p = .444). All secondary endpoints (maintenance of clinical
      stability, change in PANSS-negative symptoms, Clinical Global Impression
      Severity, and Personal and Social Performance scores) were similar in both
      treatment groups. The most common (>10% patients) treatment-emergent adverse
      events for paliperidone ER were akathisia, headache, somnolence, tremor, and
      weight gain, and for aripiprazole were worsening of schizophrenia and somnolence.
      Extrapyramidal symptoms including dystonia and hyperkinesia occurred in >2% in
      paliperidone ER-treated versus aripiprazole-treated patients. CONCLUSION:
      Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating
      adolescent schizophrenia. Both drugs showed clinically meaningful improvements in
      symptom and functional measurements and were generally tolerable. Clinical Trial
      Registration Information-An Efficacy and Safety Study of Extended-Release (ER)
      Paliperidone in Adolescent Participants With Schizophrenia;
      http://clinicaltrials.gov; NCT01009047.

PMID- 25617254
TI  - Comparison of child-parent and parent-only cognitive-behavioral therapy programs
      for anxious children aged 5 to 7 years: short- and long-term outcomes.
AB  - OBJECTIVE: Childhood anxiety disorders (AD) are prevalent, debilitating
      disorders. The most effective treatment approach for children less than 8 years
      old requires further investigation. The study's primary objective was to compare
      2 cognitive-behavioral therapy (CBT) group programs. CBT was delivered to
      children 5 to 7 years old and their parents (child-parent) or only to parents
      (parent-only), whereas children attended group sessions but did not receive CBT.
      METHOD: Using a prospective, repeated measures, longitudinal study design, 77
      children (29 male, mean age = 6.8 years; SD = 0.8 year) with AD and their parents
      participated in either a 12-week child-parent or parent-only CBT group treatment
      after a 3-month no-treatment wait-time. Well-validated treatment outcome measures
      were completed at 5 assessment time points: initial assessment, pretreatment,
      immediately posttreatment, 6 months, and 12 months posttreatment. A mixed models
      analysis was used to assess change in AD severity and global functioning
      improvements from baseline within each treatment and between treatments. RESULTS:
      No significant changes were noted in child-parent or parent-only treatment during
      the 3-month no-treatment wait time. Both treatments saw significant improvements
      posttreatment and at longer-term follow-up with significant reductions in AD
      severity measured by clinician and parent report and increases in global
      functioning. Significantly greater improvements were observed in the child-parent
      compared to the parent-only treatment. CONCLUSION: This study suggests that both
      parent-only and child-parent group CBT improves AD severity in children 5 to 7
      years old. Study results suggest that involvement of both children and parents in
      treatment is more efficacious than working with parents alone.

PMID- 25617255
TI  - More than two developmental pathways in children with gender dysphoria?

PMID- 25617257
TI  - Safety and accuracy of endovascular aneurysm repair without pre-operative and
      intra-operative contrast agent.
AB  - BACKGROUND: Severe chronic kidney disease is a major limitation for endovascular
      aortic aneurysm repair (EVAR). The aim of this study is to assess the safety and
      accuracy of fusion imaging, when performing EVAR in the absence of pre- and intra
      operative contrast agents. METHODS: From October 2013 to February 2014, every
      patient requiring EVAR and presenting with severe chronic renal impairment
      underwent a specific pre-operative imaging assessment, based on a non-enhanced CT
      scan. Centrelines were manually extracted and key points were placed at the
      landing zones. In house software makes it possible to artificially enhance the
      contrast between vascular structures and the surrounding tissue, by increasing
      the values attributed to the vascular structure voxels (500 Hounsfield units).
      EVAR was performed in a hybrid room (Zeego, Siemens), and the artificially
      enhanced CT scan was used for the construction of fusion imaging. The 3D vascular
      volume, together with the centrelines and key points, was overlaid onto the 2D
      live fluoroscopic image. RESULTS: Six patients (mean age 77.1 years) were treated
      by EVAR (5 abdominal aneurysms and 1 thoracic aneurysm), using fusion imaging
      without a contrast agent. The median pre-operative estimated glomerular
      filtration rate (eGFR) was 17.5 mL/min/1.73 m2. No contrast was used during the
      procedure. No intra-operative endoleak was observed on the duplex scan. No
      deterioration was observed in the eGFR at 1 week (eGFR = 21.7, p = .49), nor at 1
      month follow up (eGFR = 21, p = .28). The stent graft positioning error was
      assessed in terms of the difference between the effective and planned landing
      zones, measured on pre- and post-operative CT scans. The mean error was 1.3 mm at
      the proximal landing zone, and 6.5 mm at the distal landing zone. CONCLUSION:
      EVAR without the use of pre-operative and intra-operative contrast agents appears
      to be safe and accurate for patients with severe chronic kidney disease.

PMID- 25617258
TI  - Diameter-related variations of geometrical, mechanical, and mass fraction data in
      the anterior portion of abdominal aortic aneurysms.
AB  - OBJECTIVE: Maximum aortic diameter is an important measure in rupture prediction
      of abdominal aortic aneurysms (AAAs). Analyzing the variations of geometrical,
      material, and biochemical properties with increased AAA diameters advances
      understanding of the effect of lesion enlargement on patient specific vascular
      properties. METHODS: 96 AAA samples were harvested during open surgical aneurysm
      repair. Geometrical factors such as the maximum intraluminal thrombus (ILT)
      thickness, wall thickness, and AAA expansion rate were measured. Biaxial
      extension and peeling tests were performed to characterize the biaxial mechanical
      responses and to quantify the dissection properties of aneurysmal tissue. Mass
      fraction analysis quantified the dry weight percentages of elastin and collagen
      within the AAA wall. Linear regression models were used to correlate geometrical,
      mechanical, and mass fraction data with maximum AAA diameter. RESULTS: Both ILT
      thickness and AAA expansion rate increased and were positively correlated with
      maximum AAA diameter, while there was a slight increase in wall thickness for
      AAAs with a larger maximum diameter. For the biaxial mechanical responses, mean
      peak stretches and maximum tangential moduli in the circumferential and
      longitudinal axes did not correlate with maximum AAA diameters. However, the
      quantified energy to propagate tissue dissections within intima-media composites
      showed a significant inverse correlation with maximum AAA diameter. Elastin
      content decreased significantly with increasing AAA diameter. CONCLUSION: Larger
      AAA diameters are associated with thicker ILTs, higher AAA expansion rates, and
      pronounced elastin loss, and may also lead to a higher propensity for tissue
      dissection and aneurysm rupture.

PMID- 25617259
TI  - Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid
      arthritis.
AB  - A 47-year-old woman with rheumatoid arthritis (RA) treated successively with
      infliximab, abatacept, and etanercept spontaneously developed subcutaneous
      bruises and a noncompressive hematoma 11 months after starting etanercept therapy
      (50mg/week). Her prothrombin time was normal but her activated partial
      thromboplastin time was increased to 2.48 (normal range, 0.85-1.17). She had a
      circulating anticoagulant (Rosner index, 45; normal,<13) due to an anti-factor
      VIII antibody in a titer of 45 Bethesda units. Her factor VIII level was less
      than 1% (normal range, 55-150). The etanercept and leflunomide were stopped and
      prednisone was given in a daily dosage of 1mg/kg, in combination with rituximab,
      two 1-g doses at an interval of 2 weeks. After 5 months, persistence of the anti
      factor VIII antibody prompted the initiation of azathioprine therapy, 2mg/kg/d. A
      remission was achieved 9 months after the diagnosis of acquired hemophilia and
      was sustained at last follow-up after 3 years. This new case of acquired
      hemophilia in a patient with RA may reflect a simple association or an inducing
      role of etanercept.

PMID- 25617261
TI  - ?

PMID- 25617260
TI  - Adjuvant treatment with crude rhubarb for patients with systemic inflammation
      reaction syndrome/sepsis: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The objective of this study is to evaluate the benefits of adjuvant
      treatment with crude rhubarb in patients with systemic inflammation reaction
      syndrome/sepsis by conducting a meta-analysis. METHODS: We conducted a systematic
      literature search of medical electronic databases (up to October 2013). Only
      randomized controlled trials (RCTs) assessing adjuvant treatment with crude
      rhubarb in septic patients were included. RESULTS: A total of 15 RCTs with 869
      patients were identified. Pooled analysis showed that interleukin 6 (standardized
      mean differences [SMDs], -1.30; 95% confidence intervals [CIs], -1.94 to -0.66),
      tumor necrosis factor alpha (SMD, -0.95; 95% CI, -1.55 to -0.36), procalcitonin
      (SMD, -1.50; 95% CI, -2.20 to -0.80), von Willebrand factor (mean differences
      [MDs], -144.11; 95% CI, -253.87 to -34.35), prothrombin time (MD, -2.38; 95% CI, 
      2.67 to -2.10), acute physiology and chronic health evaluation II scores (MD, 
      4.51; 95% CI, -5.30 to -3.73), and gastrointestinal dysfunction (risk ratio,
      0.28; 95% CI, 0.16-0.49) were significantly reduced after treatment with crude
      rhubarb. Platelet number (MD, 58.16; 95% CI, 51.16-65.15) was significantly
      increased. However, crude rhubarb therapy did not significantly reduce 28-day
      mortality (risk ratio, 0.60; 95% CI, 0.36-1.00) compared with the usual
      treatment. CONCLUSIONS: Adjuvant treatment with crude rhubarb appears to have
      additional benefits in septic patients. Antiinflammation and
      anticoagulant/antiaggregant properties may be its potential mechanism.

PMID- 25617262
TI  - Purpura fulminans on the nose with septic abortion.

PMID- 25617264
TI  - Passive leg raising performed before a spontaneous breathing trial predicts
      weaning-induced cardiac dysfunction.
AB  - PURPOSE: Weaning-induced cardiac dysfunction is more likely to occur if the heart
      does not tolerate the changes in loading conditions induced by spontaneous
      breathing trial (SBT). We hypothesized that the presence of cardiac preload
      independence before an SBT is associated with weaning failure related to cardiac
      dysfunction. METHODS: We included 30 patients after a first failed 1-h T-tube SBT
      who had a transpulmonary thermodilution already in place. Preload independence
      [no increase in the pulse contour analysis-derived cardiac index >=10 % during
      passive leg raising (PLR)] was assessed before the second SBT. Failure of the SBT
      related to cardiac dysfunction was defined by an increase in pulmonary artery
      occlusion pressure above 18 mmHg at the end of the SBT associated with clinical
      intolerance. RESULTS: Fifty-seven SBTs were analyzed. The SBT failed in 46 cases.
      Overall, 31 failed SBTs were associated with weaning-induced cardiac dysfunction.
      During PLR, the cardiac index did not change in cases of failed SBTs with cardiac
      dysfunction, whereas it significantly increased in the other cases: 4 %
      (interquartile range, IQR 0-5) vs. 12 % (IQR 11-15), respectively. If PLR did not
      increase the cardiac index by more than 10 % before the SBT, the occurrence of
      SBT failure related to cardiac dysfunction was predicted with a sensitivity of 97
      % [95 % confidence interval (CI) 83-100], specificity of 81 % (95 % CI 61-93) and
      area under the receiver-operating characteristic curve of 0.88 (95 % CI 0.78
      0.98). CONCLUSIONS: Preload independence assessed by a negative PLR test
      performed before an SBT predicts weaning failure related to cardiac dysfunction.

PMID- 25617265
TI  - Comparing intensive care units by size or level.

PMID- 25617263
TI  - Type III procollagen as a biomarker of susceptibility to ARDS?

PMID- 25617266
TI  - Gender difference in distance of tibiofibular syndesmosis to joint dynamics of
      lower extremities during squat.
AB  - The incidence of lower extremity injury is greater in women than men, indicating
      gender difference in lower extremity function. Here we investigate the role of
      the ankle during squatting in young men and women by measuring the tibiofibular
      syndesmosis (TFS) distance and the angles of hip, ankle and knee joints. TFS
      distance was positively correlated to body mass in men, but not in women,
      suggesting some factor(s) affecting TSF distance in women. When divided into two
      groups with wide and narrow TFS distances, men apparently used ankle and hip
      joints evenly during squatting, but women, specifically those with a narrow TFS
      distance, used the hip joint more effectively than ankle. Estimated knee moment
      was positively correlated to TFS distance in women, but not in men. These results
      suggest that the women possessing a wider TFS distance use ankle function rather
      than hip junction when performing lower-extremity exercises (i.e. squatting),
      presumably accounting for the higher incidence of ankle injury in women during
      such activities. 

PMID- 25617268
TI  - Re: Extent of lymph node dissection at nephrectomy affects cancer-specific
      survival and metastatic progression in specific sub-categories of patients with
      renal cell carcinoma (RCC).

PMID- 25617267
TI  - Role of voltage-gated K(+) channels in regulating Ca(2+) entry in rat cortical
      astrocytes.
AB  - Astrocytes have multiple functions such as provision of nourishment and
      mechanical support to the nervous system, helping to clear extracellular
      metabolites of neurons and modulating synaptic transmission by releasing
      gliotransmitters. In excitable cells, voltage-gated K(+) (Kv) channels serve to
      repolarize during action potentials. Astrocytes are considered non-excitable
      cells since they are not able to generate action potentials. There is an abundant
      expression of various Kv channels in astrocytes but the functions of these Kv
      channels remain unclear. We examined whether these astrocyte Kv channels regulate
      astrocyte "excitability" in the form of cytosolic Ca(2+) signaling.
      Electrophysiological examination revealed that neonatal rat cortical astrocytes
      possessed both delayed rectifier type and A-type Kv channels. Pharmacological
      blockade of both delayed rectifier Kv channels by TEA and A-type Kv channels by
      quinidine significantly suppressed store-operated Ca(2+) influx; however, TEA
      alone or quinidine alone did not suffice to cause such suppression. TEA and
      quinidine together dramatically enhanced current injection-triggered membrane
      potential overshoot (depolarization); either drug alone caused much smaller
      enhancements. Taken together, the results suggest both delayed rectifier and A
      type Kv channels regulate astrocyte Ca(2+) signaling via controlling membrane
      potential. 

PMID- 25617269
TI  - Re: Tumor enucleation vs sharp excision in minimally invasive partial
      nephrectomy: technical benefit without impact on functional or oncologic
      outcomes.

PMID- 25617270
TI  - Re: Can selective arterial clamping with fluorescence imaging preserve kidney
      function during robotic partial nephrectomy?

PMID- 25617271
TI  - Re: A phase III trial to investigate the timing of radiotherapy for prostate
      cancer with high-risk features: background and rationale of the Radiotherapy
      Adjuvant versus Early Salvage (RAVES) trial.

PMID- 25617272
TI  - Re: AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.

PMID- 25617273
TI  - Re: Diffusion-weighted MR imaging in early assessment of tumor response to
      radiotherapy in high-risk prostate cancer.

PMID- 25617274
TI  - Re: Efficacy and safety of abiraterone acetate in an elderly patient subgroup
      (aged 75 and older) with metastatic castration-resistant prostate cancer after
      docetaxel-based chemotherapy.

PMID- 25617275
TI  - Re: Radical prostatectomy vs radiotherapy vs observation among older patients
      with clinically localized prostate cancer: a comparative effectiveness
      evaluation.

PMID- 25617276
TI  - Re: Imaging treated prostate cancer.

PMID- 25617277
TI  - Re: Longitudinal serum testosterone, luteinizing hormone, and follicle
      stimulating hormone levels in a population-based sample of long-term testicular
      cancer survivors.

PMID- 25617278
TI  - Re: A method to assess seasonality of urinary tract infections based on
      medication sales and Google trends.

PMID- 25617279
TI  - Re: Urinary diversion in patients with spinal cord injury in the United States.

PMID- 25617280
TI  - Re: Morbidity and mortality after benign prostatic hyperplasia surgery: data from
      the American College of Surgeons National Surgical Quality Improvement Program.

PMID- 25617281
TI  - Re: Are recurrence rates for "traditional" transvaginal prolapse repairs really
      that high? What does the evidence show?

PMID- 25617282
TI  - Re: Implications of the FDA statement on transvaginal placement of mesh: the
      aftermath.

PMID- 25617283
TI  - Re: Surgery versus physiotherapy for stress urinary incontinence.

PMID- 25617284
TI  - Re: Urgency after a sling: review of the management.

PMID- 25617285
TI  - Re: Association of inflammaging (inflammation + aging) with higher prevalence of
      OAB in elderly population.

PMID- 25617286
TI  - Re: Virtual reality rehabilitation as a treatment approach for older women with
      mixed urinary incontinence: a feasibility study.

PMID- 25617287
TI  - Re: Prevalence and risk factors of urinary incontinence for post-stroke
      inpatients in Southern China.

PMID- 25617288
TI  - Re: Evaluation of the learning curve for thulium VapoEnucleation of the prostate
      (ThuVEP) using a mentor-based approach.

PMID- 25617289
TI  - Re: Which laser works best for benign prostatic hyperplasia?

PMID- 25617290
TI  - Re: Transcorporal artificial urinary sphincter implantation as a salvage surgical
      procedure for challenging cases of male stress urinary incontinence: surgical
      technique and functional outcomes in a contemporary series.

PMID- 25617291
TI  - Re: Joint meeting for Bone, Reproductive and Urologic Drugs Advisory Committee
      (BRUDAC) and the Drug Safety and Risk Management Advisory Committee (DSARM AC),
      September 17, 2014.

PMID- 25617292
TI  - Re: Clinical practice patterns in the assessment and management of low
      testosterone in men: an international survey of endocrinologists.

PMID- 25617293
TI  - Re: Effect of deodorant and antiperspirant use and presence or absence of
      axillary hair on absorption of testosterone 2% solution applied to men's axillae.

PMID- 25617295
TI  - Re: Concordance between patient and physician assessment of the magnitude of
      Peyronie's disease curvature.

PMID- 25617296
TI  - Re: Men regret anabolic steroid use due to a lack of comprehension regarding the
      consequences on future fertility.

PMID- 25617297
TI  - Re: The STAGE technique (superficial tunica albuginea geometric-based excision)
      for the correction of biplanar congenital penile curvature.

PMID- 25617298
TI  - Re: Effects of work and life stress on semen quality.

PMID- 25617299
TI  - Re: Semen analysis and prediction of natural conception.

PMID- 25617300
TI  - Re: Sperm deoxyribonucleic acid damage in normozoospermic men is related to age
      and sperm progressive motility.

PMID- 25617301
TI  - Re: Increased frequency of CFTR gene mutations identified in Indian infertile men
      with non-CBAVD obstructive azoospermia and spermatogenic failure.

PMID- 25617302
TI  - Re: 45,X Karyotype in an infertile man: how is this possible?

PMID- 25617303
TI  - Re: Vasectomy and risk of aggressive prostate cancer: a 24-year follow-up study.

PMID- 25617304
TI  - Re: Delayed exstrophy repair (DER) does not compromise initial bladder
      development.

PMID- 25617305
TI  - Re: Bladder augmentation with small intestinal submucosa leads to unsatisfactory
      long-term results.

PMID- 25617306
TI  - Re: Penile duplication without removal of corporal tissue: step by step of an
      excellent cosmetic result.

PMID- 25617307
TI  - Re: Complete penile amputation during ritual neonatal circumcision and successful
      replantation using postoperative leech therapy.

PMID- 25617308
TI  - Re: Lin28 sustains early renal progenitors and induces Wilms tumor.

PMID- 25617309
TI  - Re: miR-28-5p promotes chromosomal instability in VHL-associated cancers by
      inhibiting Mad2 translation.

PMID- 25617310
TI  - Re: Cells of renin lineage take on a podocyte phenotype in aging nephropathy.

PMID- 25617311
TI  - Re: Development of a doxazosin and finasteride transdermal system for combination
      therapy of benign prostatic hyperplasia.

PMID- 25617314
TI  - Detection of relapse after hematopoietic stem cell transplantation in childhood
      by monitoring of WT1 expression and chimerism.
AB  - PURPOSE: The measurement of minimal residual disease after hematopoietic stem
      cell transplantation is crucial for the prevention of hematological relapses. But
      many methods are limited to certain groups of patients. We present a comparison
      of two markers which are universally applicable: WT1 expression and chimerism
      status. METHODS: We analyzed 1,848 peripheral blood and bone marrow samples of
      148 children, adolescents and young adults with malignant hematological diseases.
      Median follow-up time was 739 days after transplantation. RESULTS: All patients
      suffering from hematological relapse showed high WT1 levels. Approximately half
      (51%) of the 37 relapses could have been detected early through an increase in
      WT1 expression. WT1 kinetics revealed to be more specific than single elevated
      WT1 levels (p < 0.05) and chimerism analysis (p < 0.05). Combined with chimerism
      analysis, 74% of relapses were detectable in advance. Elevated WT1 expression
      levels after transplantation reached the highest sensitivity (64.9%) as a single
      marker, although differences were not significant. When the dynamics of both
      markers as well as any elevated WT1 expression were taken into account, a
      sensitivity of 81.5% and a specificity of 83.7% were obtained. CONCLUSIONS:
      Hence, we conclude that WT1 is a useful marker for monitoring of minimal residual
      disease after transplantation, if specific targets are not available. WT1
      expression and chimerism status should be mutually evaluated to decide about
      immunotherapeutic interventions aimed at preventing morphological relapse.

PMID- 25617316
TI  - Early outcomes and perioperative risk assessment in elective open
      thoracoabdominal aortic aneurysm repair: An analysis of national data over a five
      year period.
AB  - Open surgical repair of thoracoabdominal aortic aneurysms remains associated with
      significant morbidity and mortality. We sought to analyse multicentre national
      data on early outcomes of open surgical thoracoabdominal aortic aneurysm repair.
      Patients who underwent open repair of thoracoabdominal aortic aneurysm from 2005
      to 2010 were identified from the National Surgical Quality Improvement Program
      database. The primary endpoint was mortality at 30 days. Patient demographics,
      clinical variables, and intraoperative parameters were analysed by univariate and
      multivariate logistic regression methods to identify risk factors for mortality.
      Of the 682 elective repairs, 30-day outcomes of elective repairs were: 10.0%
      mortality, 21.6% surgical complications, 42.2% pulmonary complications, 17.2%
      renal complications, 12.9% cardiovascular complications, 19.2% septic
      complications, and 6.6% wound complications. Multivariate logistic regression
      analysis showed that age, ASA-class IV, dependent functional status prior to
      surgery, and operation time are independent risk factors for mortality. Our study
      found a higher rate of mortality nationwide, as compared to several previous
      single center studies. 

PMID- 25617315
TI  - Alzheimer-associated Abeta oligomers impact the central nervous system to induce
      peripheral metabolic deregulation.
AB  - Alzheimer's disease (AD) is associated with peripheral metabolic disorders.
      Clinical/epidemiological data indicate increased risk of diabetes in AD patients.
      Here, we show that intracerebroventricular infusion of AD-associated Abeta
      oligomers (AbetaOs) in mice triggered peripheral glucose intolerance, a
      phenomenon further verified in two transgenic mouse models of AD. Systemically
      injected AbetaOs failed to induce glucose intolerance, suggesting AbetaOs target
      brain regions involved in peripheral metabolic control. Accordingly, we show that
      AbetaOs affected hypothalamic neurons in culture, inducing eukaryotic translation
      initiation factor 2alpha phosphorylation (eIF2alpha-P). AbetaOs further induced
      eIF2alpha-P and activated pro-inflammatory IKKbeta/NF-kappaB signaling in the
      hypothalamus of mice and macaques. AbetaOs failed to trigger peripheral glucose
      intolerance in tumor necrosis factor-alpha (TNF-alpha) receptor 1 knockout mice.
      Pharmacological inhibition of brain inflammation and endoplasmic reticulum stress
      prevented glucose intolerance in mice, indicating that AbetaOs act via a central
      route to affect peripheral glucose homeostasis. While the hypothalamus has been
      largely ignored in the AD field, our findings indicate that AbetaOs affect this
      brain region and reveal novel shared molecular mechanisms between hypothalamic
      dysfunction in metabolic disorders and AD. 

PMID- 25617317
TI  - Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse
      survival through the amelioration of intestinal and bone marrow damage.
AB  - The identification of an agent effective for the treatment of intestinal and bone
      marrow injury following radiation exposure remains a major issue in radiological
      medicine. In this study, we evaluated the therapeutic impact of single agent or
      combination treatments with 2-(3-aminopropylamino) ethylsulphanyl phosphonic acid
      (WR-2721) and peptidoglycan (PGN, a toll-like receptor 2 (TLR-2) agonist) on
      radiation-induced injury of the intestine and bone marrow in lethally irradiated
      male C57BL/6 mice. A dose of 3 mg of WR-2721 per mouse (167 mg/kg,
      intraperitoneally) was given 30 min before irradiation, and 30 MUg of PGN per
      mouse (1.7 mg/kg) was injected intraperitoneally 24 h after 10 Gy irradiation.
      Bone marrow cluster of differentiation (CD)45(+) and CD34(+) markers of multiple
      haematopoietic lineages, number of granulocyte-erythroid-macrophage-megakaryocyte
      (GEMM) progenitor colonies, bone marrow histopathology, leucine-rich repeat
      containing G-protein-coupled receptor 5 (Lgr5) expression in the intestines,
      xylose absorption and intestinal histopathology were all assessed at various time
      points after irradiation. Furthermore, nuclear factor kappa B (NF-kappaB) p65
      protein in the ileum was stained by immunofluorescent labelling. PGN-treated
      irradiated mice showed an increase in CD45(+)CD34(+) cells compared with
      untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05).
      Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic
      radio-protective effect in nucleated cells in the bone marrow, including GEMM
      progenitors and CD45(+)CD34(+) cells 4 days after 10 Gy IR. Single agent PGN or
      WR-2721 treatment after 10 Gy IR clearly increased Lgr5-positive pit cells (P <
      0.05) and xylose absorption (P < 0.05). However only PGN and WR-2721 combination
      treatment markedly increased villus height (P < 0.05), number of crypts (P <
      0.05) and whole-body weights after 10 Gy whole-body irradiation (WBI). The NF
      kappaB p65 subunit was translocated to the nucleus, and phosphate-IkappaBalpha
      (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which
      indicates that these two agents act synergistically through the activation of the
      NF-kappaB pathway. Administration of PGN in combination with WR-2721 was
      demonstrated to have a synergistic effect on the increase in haematopoietic cells
      and intestinal reconstitution, as well as improved survival in lethally
      irradiated mice, but resulted in some degree of an immune disorder. 

PMID- 25617318
TI  - OsJAZ9 acts as a transcriptional regulator in jasmonate signaling and modulates
      salt stress tolerance in rice.
AB  - The basic functions of plant-specific TIFY proteins as transcriptional regulators
      have been reported in plants. Some TIFY genes are responsive to abiotic stresses,
      but the functions of these genes in stress tolerance have seldom been reported.
      OsJAZ9 is a member of the JAZ subfamily which belongs to the TIFY gene family in
      rice (Oryza sativa). Suppression of OsJAZ9 resulted in reduced salt tolerance.
      The altered salt tolerance was mainly due to changes in ion (especially K(+))
      homeostasis, which was supported by the altered expression levels of several ion
      transporter genes. The OsJAZ9-suppression rice plants showed increased
      sensitivity to jasmonic acid (JA) treatment. OsJAZ9 interacts with OsCOI1a, a
      component of the SCF(COI1) E3 ubiquitin ligase complex, in a coronatine-dependent
      manner, suggesting that OsJAZ9 is involved in the regulation of JA signaling.
      OsJAZ9 interacts with several bHLH transcription factors including OsbHLH062 via
      the Jas domain. OsbHLH062 can bind to an E-box in the promoters of the ion
      transporter genes such as OsHAK21, and most of these ion transporter genes are
      responsive to JA treatment. We found that OsJAZ9 can also interact with OsNINJA,
      a rice homolog of the Arabidopsis thaliana transcriptional repressor NINJA in JA
      signaling. Both OsJAZ9 and OsNINJA (Novel Interactor of JAZ) repressed OsbHLH062
      mediated transcription activation. These results together suggest that OsJAZ9
      acts as a transcriptional regulator by forming a transcriptional regulation
      complex with OsNINJA and OsbHLH to fine tune the expression of JA-responsive
      genes involved in salt stress tolerance in rice. 

PMID- 25617319
TI  - Characterization of the adaptive response of grapevine (cv. Tempranillo) to UV-B
      radiation under water deficit conditions.
AB  - This work aims to characterize the physiological response of grapevine (Vitis
      vinifera L.) cv. Tempranillo to UV-B radiation under water deficit conditions.
      Grapevine fruit-bearing cuttings were exposed to three levels of supplemental
      biologically effective UV-B radiation (0, 5.98 and 9.66kJm(-2)day(-1)) and two
      water regimes (well watered and water deficit), in a factorial design, from fruit
      set to maturity under glasshouse-controlled conditions. UV-B induced a transient
      decrease in net photosynthesis (Anet), actual and maximum potential efficiency of
      photosystem II, particularly on well watered plants. Methanol extractable UV-B
      absorbing compounds (MEUVAC) concentration and superoxide dismutase activity
      increased with UV-B. Water deficit effected decrease in Anet and stomatal
      conductance, and did not change non-photochemical quenching and the de
      epoxidation state of xanthophylls, dark respiration and photorespiration being
      alternative ways to dissipate the excess of energy. Little interactive effects
      between UV-B and drought were detected on photosynthesis performance, where the
      impact of UV-B was overshadowed by the effects of water deficit. Grape berry
      ripening was strongly delayed when UV-B and water deficit were applied in
      combination. In summary, deficit irrigation did not modify the adaptive response
      of grapevine to UV-B, through the accumulation of MEUVAC. However, combined
      treatments caused additive effects on berry ripening. 

PMID- 25617320
TI  - Erianthus arundinaceus HSP70 (EaHSP70) overexpression increases drought and
      salinity tolerance in sugarcane (Saccharum spp. hybrid).
AB  - Heat shock proteins (HSPs) have a major role in stress tolerance mechanisms in
      plants. Our studies have shown that the expression of HSP70 is enhanced under
      water stress in Erianthus arundinaceus. In this paper, we evaluate the effects of
      overexpression of EaHSP70 driven by Port Ubi 2.3 promoter in sugarcane. The
      transgenic events exhibit significantly higher gene expression, cell membrane
      thermostability, relative water content, gas exchange parameters, chlorophyll
      content and photosynthetic efficiency. The overexpression of EaHSP70 transgenic
      sugarcane led to the upregulation of stress-related genes. The transformed
      sugarcane plants had better chlorophyll retention and higher germination ability
      than control plants under salinity stress. Our results suggest that EaHSP70 plays
      an important role in sugarcane acclimation to drought and salinity stresses and
      its potential for genetic engineering of sugarcane for drought and salt
      tolerance. 

PMID- 25617321
TI  - Consequences of hybridization and heterozygosity on plant vigor and phenotypic
      stability.
AB  - The genomic makeup and phenotypes of plants are diversifying, in part due to
      artificial or natural selection in agricultural and natural environments.
      Utilization of these variations to enhance crop productivity requires an
      understanding of the relationships between genotype and phenotype in inbreds and
      hybrids derived from crosses between these populations. This review highlights
      recent studies on hybrid vigor (heterosis) and the related phenomenon of hybrid
      weakness - two types of non-additive inheritance. Heterosis is a phenomenon
      whereby the phenotype of first-generation hybrids is superior to that of their
      parents. Intralocus interactions between alleles, complementation of dominant
      alleles, or inter-loci epistatic interactions are genetic mechanisms that may
      cause non-additive phenotypic inheritance in hybrids. However, there are
      different views on what portion of the heterotic variation is modulated by each
      of these mechanisms. Another aspect of plant vigor is phenotypic stability or
      robustness in different environments and how this is influenced by gene
      heterozygosity. Hybrids are not necessarily more phenotypically stable than
      inbreds since local heterozygosity might be associated with negative effects on
      biochemical activities. This review integrates genetic and biochemical
      considerations to illustrate how these relationships may be tightly linked with
      breeding system and sequence divergence. 

PMID- 25617322
TI  - Mutation at the tomato excessive number of floral organs (ENO) locus impairs
      floral meristem development, thus promoting an increased number of floral organs
      and fruit size.
AB  - A novel tomato (Solanum lycopersicum L.) mutant affected in reproductive
      development, excessive number of floral organs (eno), is described in this study.
      The eno plants yielded flowers with a higher number of floral organs in the three
      innermost floral whorls and larger fruits than those found in wild-type plants.
      Scanning-electron microscopy study indicated that the rise in floral organ number
      and fruit size correlates with an increased size of floral meristem at early
      developmental stages. It has been reported that mutation at the FASCIATED (FAS)
      gene causes the development of flowers with supernumerary organs; however,
      complementation test and genetic mapping analyses proved that ENO is not an
      allele of the FAS locus. Furthermore, expression of WUSCHEL (SlWUS) and INHIBITOR
      OF MERISTEM ACTIVITY (IMA), the two main regulators of floral meristem activity
      in tomato, is altered in eno but not in fas flowers indicating that ENO could
      exert its function in the floral meristem independently of FAS. Interestingly,
      the eno mutation delayed the expression of IMA leading to a prolonged expression
      of SlWUS, which would explain the greater size of floral meristem. Taken
      together, results showed that ENO plays a significant role in the genetic pathway
      regulating tomato floral meristem development. 

PMID- 25617323
TI  - Ectopic expression of myo-inositol 3-phosphate synthase induces a wide range of
      metabolic changes and confers salt tolerance in rice.
AB  - Salt stress is an important factor that limits crop production worldwide. The
      salt tolerance of plants is a complex biological process mediated by changes in
      gene expression and metabolite composition. The enzyme myo-inositol 3-phosphate
      synthase (MIPS; EC 5.5.1.4) catalyzes the first step of myo-inositol
      biosynthesis, and overexpression of the MIPS gene enhances salt stress tolerance
      in several plant species. In this study, we performed metabolite profiling of
      both MIPS-overexpressing and wild-type rice. The enhanced salt stress tolerance
      of MIPS-overexpressing plants was clear based on growth and the metabolites under
      salt stress. We found that constitutive overexpression of the rice MIPS gene
      resulted in a wide range of metabolic changes. This study demonstrates for the
      first time that overexpression of the MIPS gene increases various metabolites
      responsible for protecting plants from abiotic stress. Activation of both basal
      metabolism, such as glycolysis, the pentose phosphate pathway, and the
      tricarboxylic acid cycle, and inositol metabolism is induced in MIPS
      overexpressing plants. We discuss the relationship between the metabolic changes
      and the improved salt tolerance observed in transgenic rice. 

PMID- 25617324
TI  - Correlations of carotenoid content and transcript abundances for fibrillin and
      carotenogenic enzymes in Capsicum annum fruit pericarp.
AB  - The fruits of Capsicum spp. are especially rich sites for carotenoid synthesis
      and accumulation, with cultivar-specific carotenoid accumulation profiles.
      Differences in chromoplast structure as well as carotenoid biosynthesis are
      correlated with distinct carotenoid accumulations and fruit color. In the present
      study, the inheritance of chromoplast shape, carotenoid accumulation profiles,
      and transcript levels of four genes were measured. Comparisons of these traits
      were conducted using fruit from contrasting variants, Costeno Amarillo versus
      Costeno Red, and from F1 hybrids; crosses between parental lines with novel
      versions of these traits. Intermediate chromoplast shapes were observed in the
      F1, but no association between specific carotenoid accumulation and chromoplast
      shape was detected. Increased total carotenoid content was associated with
      increased beta-carotene and violaxanthin content. Transcript levels for phytoene
      synthase (Psy) and beta-carotene hydroxylase (CrtZ-2) were positively correlated
      with increased levels of specific carotenoids. No correlation was detected
      between transcript levels of capsanthin/capsorubin synthase (Ccs) and carotenoid
      composition or chromoplast shape. Transcript levels of fibrillin, were
      differentially correlated with specific carotenoids, negatively correlated with
      accumulation of capsanthin, and positively correlated with violaxanthin. The
      regulation of carotenoid accumulation in chromoplasts in Capsicum fruit continues
      to be a complex process with multiple steps for control. 

PMID- 25617325
TI  - Photosynthesizing on metal excess: copper differently induced changes in various
      photosynthetic parameters in copper tolerant and sensitive Silene paradoxa L.
      populations.
AB  - This work investigated Cu-induced changes in photosynthetic activity in
      contrasting populations of Silene paradoxa L. A metallicolous Cu-tolerant
      population and a non-metallicolous sensitive population were grown in hydroponics
      and exposed to different CuSO4 treatments for different times. Copper
      accumulation, MDA concentrations, and several photosynthetic parameters were
      measured to assess different effects of Cu exposure on plants from the two
      populations. A more efficient ability to photosynthesize in the presence of Cu
      excess was showed by the Cu-tolerant population with respect to the sensitive
      one. Interestingly, Cu-imposed limitations were present not only at a different
      degree, but also of different nature in the two populations. In the tolerant
      population, the most limiting factor to photosynthesis seemed to be Cu-imposed
      stomatal closure, whereas Cu-mediated biochemical limitation was scarce and Cu
      mediated reduction in mesophyll conductance almost non-existent. In the sensitive
      population, Cu largely affected all the measured parameters, so that its
      photosynthetic activity experienced any kind of limitation, diffusional and
      especially biochemical. The lower Cu concentrations accumulated in the tolerant
      plant could be one of the factors concurring to the reported differences in
      photosynthetic activity, but also a higher capacity of internal detoxification
      and compartmentalization of the metal could not be excluded. 

PMID- 25617326
TI  - Maturation of nematode-induced galls in Medicago truncatula is related to water
      status and primary metabolism modifications.
AB  - Root-knot nematodes are obligatory plant parasitic worms that establish and
      maintain an intimate relationship with their host plants. During a compatible
      interaction, these nematodes induce the redifferentiation of root cells into
      multinucleate and hypertrophied giant cells (GCs). These metabolically active
      feeding cells constitute the exclusive source of nutrients for the nematode. We
      analyzed the modifications of water status, ionic content and accumulation of
      metabolites in development and mature galls induced by Meloidogyne incognita and
      in uninfected roots of Medicago truncatula plants. Water potential and osmotic
      pressure are significantly modified in mature galls compared to developing galls
      and control roots. Ionic content is significantly modified in galls compared to
      roots. Principal component analyses of metabolite content showed that mature gall
      metabolism is significantly modified compared to developing gall metabolism. The
      most striking differences were the three-fold increase of trehalose content
      associated to the five-fold diminution in glucose concentration in mature galls.
      Gene expression analysis showed that trehalose accumulation was, at least,
      partially linked to a significantly lower expression of the trehalase gene in
      mature galls. Our results point to significant modifications of gall physiology
      during maturation. 

PMID- 25617328
TI  - Inter-rater reliability of J-point location and measurement of the magnitude of
      ST segment elevation at the J-point on ECGs of STEMI patients by emergency
      department doctors.
AB  - INTRODUCTION AND OBJECTIVES: Identification of the J-point and measurement of ST
      segment elevation at the J-point are important for the diagnosis of ST-elevation
      myocardial infarction (STEMI). We conducted a study to determine the inter-rater
      reliability (IRR) of J-point location and measurement of the magnitude of ST
      elevation at the J-point on ECGs of patients with STEMI by emergency department
      (ED) doctors. SUBJECTS AND METHODS: Each participant examined 20 STEMI ECGs
      during a 1-month period in 2013. The participants were required to locate the J
      point by selecting the small 1 mm square within which the J-point is located and
      measure the magnitude of ST elevation at the J-point identified (rounded up to
      the nearest 0.5 mm). The intraclass correlation coefficient (ICC) was calculated
      to assess the IRR. RESULTS: Thirty doctors participated. The ICC assessing the
      degree to which all participants provided agreement in their assessment of the
      location of J-points across ECGs was 0.85 (95% CI 0.75 to 0.93), which is in the
      excellent range. The ICC for assessing the magnitude of ST elevation was 0.97
      (95% CI 0.94 to 0.98), indicating excellent agreement as well. CONCLUSIONS: ED
      doctors show a high level of agreement when determining the location of J-points
      and measuring the magnitude of ST elevation at those J-points on ECGs of patients
      with STEMI. The findings support the measurement of ST segment elevation at the J
      point in STEMI cases and should be regarded as a consistent standard to avoid
      confusion.

PMID- 25617327
TI  - The effect of Midazolam and Propranolol on fear memory reconsolidation in ethanol
      withdrawn rats: influence of d-cycloserine.
AB  - BACKGROUND: Withdrawal from chronic ethanol facilitates the formation of
      contextual fear memory and delays the onset to extinction, with its retrieval
      promoting an increase in ethanol consumption. Consequently, manipulations aimed
      to reduce these aversive memories, may be beneficial in the treatment of alcohol
      discontinuation symptoms. Related to this, pharmacological memory reconsolidation
      blockade has received greater attention due to its therapeutic potential.
      METHODS: Here, we examined the effect of post-reactivation amnestic treatments
      such as Midazolam (MDZ, 3 mg/kg i.p) and Propranolol (PROP, 5 mg/kg i.p) on
      contextual fear memory reconsolidation in ethanol- withdrawn (ETOH) rats. Next,
      we examined whether the activation of N-methyl-D-aspartate (NMDA) receptors
      induced by d-cycloserine (DCS, 5 mg/kg i.p., a NMDA partial agonist) before
      memory reactivation can facilitate the disruptive effect of PROP and MDZ on fear
      memory in ETOH rats. RESULTS: We observed a resistance to the disruptive effect
      of both MDZ and PROP following memory reactivation. Although intra-basolateral
      amygdala (BLA; 1.25 ug/side) and systemic PROP administration attenuated fear
      memory in DCS pre-treated ETOH rats, DCS/MDZ treatment did not affect memory in
      these animals. Finally, a decrease of both total and surface protein expression
      of the alpha1 GABAA receptor (GABAA-R) subunit in BLA was found in the ETOH rats.
      CONCLUSIONS: Ethanol withdrawal facilitated the formation of fear memory
      resistant to labilization post-reactivation. DCS administration promoted the
      disruptive effect of PROP on memory reconsolidation in ETOH rats. The resistance
      to MDZ's disruptive effect on fear memory reconsolidation may be, at least in
      part, associated with changes in the GABAA-R composition induced by chronic
      ethanol administration/withdrawal.

PMID- 25617341
TI  - Assessing the reliability and validity of direct observation and traffic camera
      streams to measure helmet and motorcycle use.
AB  - There is a need to develop motorcycle helmet surveillance approaches that are
      less labour intensive than direct observation (DO), which is the commonly
      recommended but never formally validated approach, particularly in developing
      settings. This study sought to assess public traffic camera feeds as an
      alternative to DO, in addition to the reliability of DO under field conditions.
      DO had high inter-rater reliability, kappa=0.88 and 0.84, respectively, for cycle
      type and helmet type, which reinforces its use as a gold standard. However,
      traffic camera-based data collection was found to be unreliable, with kappa=0.46
      and 0.53 for cycle type and helmet type. When bicycles, motorcycles and scooters
      were classified based on traffic camera streams, only 68.4% of classifications
      concurred with those made via DO. Given the current technology, helmet
      surveillance via traffic camera streams is infeasible, and there remains a need
      for innovative traffic safety surveillance approaches in low-income urban
      settings. 

PMID- 25617342
TI  - System facilitators and barriers to discussing older driver safety in primary
      care settings.
AB  - BACKGROUND: Primary care physicians play a leading role in counselling older
      drivers, but discussions often do not occur until safety concerns arise. Prior
      work suggests that routine questioning about driving might facilitate these
      difficult conversations. OBJECTIVE: To explore system-level factors affecting
      driving discussions in primary care settings, in order to inform the design and
      implementation of a programme supporting routine conversations. METHODS: This
      qualitative descriptive study used iterative interviews with providers
      (physicians, nurses, medical assistants, social workers, and administrative
      staff) working at two clinics (one geriatric, one general internal medicine) at a
      tertiary-care teaching hospital. General inductive techniques in transcript
      analysis were used to identify stakeholder-perceived system-level barriers and
      facilitators to routine conversations with older drivers. RESULTS: From 15
      interviews, four themes emerged: (1) complexity of defined provider roles within
      primary care setting (which can both support team work and hamper efficiency);
      (2) inadequate resources to support providers (including clinical prompts, local
      guides, and access to social workers and driving specialists); (3) gaps in
      education of providers and patients about discussing driving; and (4) suggested
      models to enhance provider conversations with older drivers (including following
      successful examples and using defined pathways integrated into the electronic
      medical record). A fifth theme was that participants characterised their
      experiences in terms of current and ideal states. CONCLUSIONS: Physicians have
      been tasked with assessing older driver safety and guiding older patients through
      the process of 'driving retirement.' Attention to system-level factors such as
      provider roles, resources, and training can support them in this process.

PMID- 25617343
TI  - Acute kidney injury and chronic kidney disease.

PMID- 25617344
TI  - Segmental Arterial Mediolysis in Pigs Presenting With Renal Infarcts.
AB  - Segmental arterial mediolysis, a rare arteriopathy first reported in humans, is
      described in the kidneys of 36 pigs slaughtered in an abattoir in Jutland,
      Denmark. The kidney changes presented themselves macroscopically as one or more
      cortical wedge-shaped hemorrhagic or pale lesions. The arterial lesions involved
      the interlobar and arcuate arteries and exhibited injurious and reparative phases
      of development. Two types of injurious lesions occurred: (1) a tearing separation
      of the outer media from the adventitia with fibrin, erythrocytes, and edema fluid
      filling the formed space, causing collapse of the arterial wall, and (2) outer
      and mid-medial foci showing irregularly bordered cytoplasmic vacuolar change
      containing membranous and organelle debris or smooth muscle shrinkage with
      nuclear loss. In the reparative phase, granulation tissue filled and expanded
      tear sites and zones of arterial medial muscle loss and extended into the
      adventitia and through the intima into the arterial lumen. Sequelae, including
      dissecting hematomas and arterial occlusions causing renal infarcts, were found.
      Although repartitioning agents widely used in animal husbandry in many countries
      may potentially cause segmental arterial mediolysis, no such link could be
      identified. The causation of segmental arterial mediolysis in these pigs is
      currently unknown but is being further investigated. 

PMID- 25617345
TI  - Pododermatitis in Captive and Free-Ranging Greater Flamingos (Phoenicopterus
      roseus).
AB  - Pododermatitis is frequent in captive flamingos worldwide, but little is known
      about the associated histopathologic lesions. Involvement of a papillomavirus or
      herpesvirus has been suspected. Histopathologic evaluation and viral assessment
      of biopsies from 19 live and 10 dead captive greater flamingos were performed.
      Selected samples were further examined by transmission electron microscopy and
      immunohistochemistry. Feet from 10 dead free-ranging greater flamingos were also
      evaluated. The histologic appearance of lesions of flamingos of increasing age
      was interpreted as the progression of pododermatitis. Mild histologic lesions
      were seen in a 3-week-old flamingo chick with no macroscopic lesions, and these
      were characterized by Micrococcus-like bacteria in the stratum corneum associated
      with exocytosis of heterophils. The inflammation associated with these bacteria
      may lead to further histologic changes: irregular columnar proliferations,
      papillary squirting, and dyskeratosis. In more chronic lesions, hydropic
      degeneration of keratinocytes, epidermal hyperplasia, and dyskeratosis were seen
      at the epidermis, as well as proliferation of new blood vessels and increased
      intercellular matrix in the dermis. Papillomavirus DNA was not identified in any
      of the samples, while herpesvirus DNA was seen only in a few cases; therefore,
      these viruses were not thought to be the cause of the lesions. Poor skin health
      through suboptimal husbandry may weaken the epidermal barrier and predispose the
      skin to invasion of Micrococcus-like bacteria. Histologic lesions were identified
      in very young flamingos with no macroscopic lesions; this is likely to be an
      early stage lesion that may progress to macroscopic lesions. 

PMID- 25617346
TI  - The epigenetic clock is correlated with physical and cognitive fitness in the
      Lothian Birth Cohort 1936.
AB  - BACKGROUND: The DNA methylation-based 'epigenetic clock' correlates strongly with
      chronological age, but it is currently unclear what drives individual
      differences. We examine cross-sectional and longitudinal associations between the
      epigenetic clock and four mortality-linked markers of physical and mental
      fitness: lung function, walking speed, grip strength and cognitive ability.
      METHODS: DNA methylation-based age acceleration (residuals of the epigenetic
      clock estimate regressed on chronological age) were estimated in the Lothian
      Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years.
      General cognitive ability, walking speed, lung function and grip strength were
      measured concurrently. Cross-sectional correlations between age acceleration and
      the fitness variables were calculated. Longitudinal change in the epigenetic
      clock estimates and the fitness variables were assessed via linear mixed models
      and latent growth curves. Epigenetic age acceleration at age 70 was used as a
      predictor of longitudinal change in fitness. Epigenome-wide association studies
      (EWASs) were conducted on the four fitness measures. RESULTS: Cross-sectional
      correlations were significant between greater age acceleration and poorer
      performance on the lung function, cognition and grip strength measures (r range: 
      0.07 to -0.05, P range: 9.7 x 10(-3) to 0.024). All of the fitness variables
      declined over time but age acceleration did not correlate with subsequent change
      over 6 years. There were no EWAS hits for the fitness traits. CONCLUSIONS:
      Markers of physical and mental fitness are associated with the epigenetic clock
      (lower abilities associated with age acceleration). However, age acceleration
      does not associate with decline in these measures, at least over a relatively
      short follow-up.

PMID- 25617347
TI  - From intracellular signaling to population oscillations: bridging size- and time
      scales in collective behavior.
AB  - Collective behavior in cellular populations is coordinated by biochemical
      signaling networks within individual cells. Connecting the dynamics of these
      intracellular networks to the population phenomena they control poses a
      considerable challenge because of network complexity and our limited knowledge of
      kinetic parameters. However, from physical systems, we know that behavioral
      changes in the individual constituents of a collectively behaving system occur in
      a limited number of well-defined classes, and these can be described using simple
      models. Here, we apply such an approach to the emergence of collective
      oscillations in cellular populations of the social amoeba Dictyostelium
      discoideum. Through direct tests of our model with quantitative in vivo
      measurements of single-cell and population signaling dynamics, we show how a
      simple model can effectively describe a complex molecular signaling network at
      multiple size and temporal scales. The model predicts novel noise-driven single
      cell and population-level signaling phenomena that we then experimentally
      observe. Our results suggest that like physical systems, collective behavior in
      biology may be universal and described using simple mathematical models. 

PMID- 25617348
TI  - Loss of Gab1 adaptor protein in hepatocytes aggravates experimental liver
      fibrosis in mice.
AB  - Grb2-associated binder 1 (Gab1) adaptor protein amplifies signals downstream of a
      broad range of growth factors/receptor tyrosine kinases. Although these signals
      are implicated in liver fibrogenesis, the role of Gab1 remains unclear. To
      elucidate the role of Gab1, liver fibrosis was examined in hepatocyte-specific
      Gab1-conditional knockout (Gab1CKO) mice upon bile duct ligation (BDL). Gab1CKO
      mice developed exacerbated liver fibrosis with activation of hepatic
      myofibroblasts after BDL compared with control mice. The antifibrotic role of
      hepatocyte Gab1 was further confirmed by another well-established mouse model of
      liver fibrosis using chronic injections of carbon tetrachloride. After BDL,
      Gab1CKO mice also displayed exacerbated liver injury, decreased hepatocyte
      proliferation, and enhanced liver inflammation. Furthermore, cDNA microarray
      analysis was used to investigate the potential molecular mechanisms of the Gab1
      mediated signal in liver fibrosis, and the fibrosis-promoting factor chemokine (C
      C motif) ligand 5 (Ccl5) was identified as upregulated in the livers of Gab1CKO
      mice following BDL. Interestingly, in vitro studies using primary hepatocytes
      isolated from control and Gab1CKO mice revealed that the loss of Gab1 resulted in
      increased hepatocyte CCL5 synthesis upon lipopolysaccharide stimulation. Finally,
      pharmacological antagonism of CCL5 reduced BDL-induced liver fibrosis in Gab1CKO
      mice. In conclusion, our results demonstrate that hepatocyte Gab1 is required for
      liver fibrosis and that hepatocyte CCL5 could be an important contributor to this
      process. Thus, we present a novel antifibrotic function of hepatocyte Gab1 in
      liver fibrogenesis.

PMID- 25617351
TI  - Should a medical journal ever publish a political paper?

PMID- 25617352
TI  - European-added value for public health.

PMID- 25617350
TI  - Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle.
AB  - Preliminary proteomics studies between tonic vs. phasic smooth muscles identified
      three distinct protein spots identified to be those of transgelin (SM22). The
      latter was found to be distinctly downregulated in the internal anal sphincter
      (IAS) vs. rectal smooth muscle (RSM) SMC. The major focus of the present studies
      was to examine the differential molecular control mechanisms by SM22 in the
      functionality of truly tonic smooth muscle of the IAS vs. the adjoining phasic
      smooth muscle of the RSM. We monitored SMC lengths before and after incubation
      with pFLAG-SM22 (for SM22 overexpression), and SM22 small-interfering RNA. pFLAG
      SM22 caused concentration-dependent and significantly greater relaxation in the
      IAS vs. the RSM SMCs. Conversely, temporary silencing of SM22 caused contraction
      in both types of the SMCs. Further studies revealed a significant reverse
      relationship between the levels of SM22 phosphorylation and the amount of SM22
      actin binding in the IAS and RSM SMC. Data showed higher phospho-SM22 levels and
      decreased SM22-actin binding in the IAS, and reverse to be the case in the RSM
      SMCs. Experiments determining the mechanism for SM22 phosphorylation in these
      smooth muscles revealed that Y-27632 (Rho kinase inhibitor) but not Go-6850
      (protein kinase C inhibitor) caused concentration-dependent decreased
      phosphorylation of SM22. We speculate that SM22 plays an important role in the
      regulation of basal tone via Rho kinase-induced phosphorylation of SM22.

PMID- 25617349
TI  - Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula
      mice.
AB  - Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in
      2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on
      the effect of apoA-V on postprandial plasma TG, an independent predictor for
      atherosclerosis. Overexpressing apoA-V in mice suppresses postprandial TG, but
      mechanisms focus on increased lipolysis or clearance of remnant particles.
      Unknown is whether apoA-V suppresses the absorption of dietary lipids by the gut.
      This study examines how apoA-V deficiency affects the steady-state absorption and
      lymphatic transport of dietary lipids in chow-fed mice. Using apoA-V knockout
      (KO, n = 8) and wild-type (WT, n = 8) lymph fistula mice, we analyzed the uptake
      and lymphatic transport of lipids during a continuous infusion of an emulsion
      containing [(3)H]triolein and [(14)C]cholesterol. ApoA-V KO mice showed a twofold
      increase in (3)H (P < 0.001) and a threefold increase in (14)C (P < 0.001)
      transport into the lymph compared with WT. The increased lymphatic transport was
      accompanied by a twofold reduction (P < 0.05) in mucosal (3)H, suggesting that
      apoA-V KO mice more rapidly secreted [(3)H]TG out of the mucosa into the lymph.
      ApoA-V KO mice also produced chylomicrons more rapidly than WT (P < 0.05), as
      measured by the transit time of [(14)C]oleic acid from the intestinal lumen to
      lymph. Interestingly, apoA-V KO mice produced a steadily increasing number of
      chylomicron particles over time, as measured by lymphatic apoB output. The data
      suggest that apoA-V suppresses the production of chylomicrons, playing a
      previously unknown role in lipid metabolism that may contribute to the
      postprandial hypertriglyceridemia associated with apoA-V deficiency. 

PMID- 25617353
TI  - Cultural, social and intrapersonal factors associated with clusters of co
      occurring health-related behaviours among adolescents.
AB  - BACKGROUND: Adverse health-related behaviours (HRBs) have been shown to co-occur
      in adolescents. Evidence lacks on factors associated with these co-occurring
      HRBs. The Theory of Triadic Influence (TTI) offers a route to categorize these
      determinants according to type (social, cultural and intrapersonal) and distance
      in the causal pathway (ultimate or distal). Our aims were to identify cultural,
      social and intrapersonal factors associated with co-occurring HRBs and to assess
      the relative importance of ultimate and distal factors for each cluster of co
      occurring HRBs. METHODS: Respondents concerned a random sample of 898 adolescents
      aged 12-18 years, stratified by age, sex and educational level of head of
      household. Data were collected via face-to-face computer-assisted interviewing
      and internet questionnaires. Analyses were performed for young (12-15 years) and
      late (16-18 years) adolescents regarding two and three clusters of HRB,
      respectively. RESULTS: For each cluster of HRBs (e.g. smoking, delinquency),
      associated factors were found. These accounted for 27 to 57% of the total
      variance per cluster. Factors came in particular from the intrapersonal stream of
      the TTI at the ultimate level and the social stream at the distal level.
      Associations were strongest for parenting practices, risk behaviours of friends
      and parents and self-control. CONCLUSION: Results of this study confirm that it
      is possible to identify a selection of cultural, social and intrapersonal factors
      associated with co-occurring HRBs among adolescents.

PMID- 25617354
TI  - European public health news.

PMID- 25617355
TI  - Recent progress in understanding transcription factor binding specificity.

PMID- 25617356
TI  - The impact of capillary dilation on the distribution of red blood cells in
      artificial networks.
AB  - Recent studies suggest that pericytes around capillaries are contractile and able
      to alter the diameter of capillaries. To investigate the effects of capillary
      dilation on network dynamics, we performed simulations in artificial capillary
      networks of different sizes and complexities. The unequal partition of hematocrit
      at diverging bifurcations was modeled by assuming that each red blood cell (RBC)
      enters the branch with the faster instantaneous flow. Network simulations with
      and without RBCs were performed to investigate the effect of local dilations. The
      results showed that the increase in flow rate due to capillary dilation was less
      when the effects of RBCs are included. For bifurcations with sufficient RBCs in
      the parent vessel and nearly equal flows in the branches, the flow rate in the
      dilated branch did not increase. Instead, a self-regulation of flow was observed
      due to accumulation of RBCs in the dilated capillary. A parametric study was
      performed to examine the dependence on initial capillary diameter, dilation
      factor, and tube hematocrit. Furthermore, the conditions needed for an efficient
      self-regulation mechanism are discussed. The results support the hypothesis that
      RBCs play a significant role for the fluid dynamics in capillary networks and
      that it is crucial to consider the blood flow rate and the distribution of RBCs
      to understand the supply of oxygen in the vasculature. Furthermore, our results
      suggest that capillary dilation/constriction offers the potential of being an
      efficient mechanism to alter the distribution of RBCs locally and hence could be
      important for the local regulation of oxygen delivery.

PMID- 25617357
TI  - The beneficial effects of AMP kinase activation against oxidative stress are
      associated with prevention of PPARalpha-cyclophilin D interaction in
      cardiomyocytes.
AB  - AMP kinase (AMPK) plays an important role in the regulation of energy metabolism
      in cardiac cells. Furthermore, activation of AMPK protects the heart from
      myocardial infarction and heart failure. The present study examines whether or
      not AMPK affects the peroxisome proliferator-activated receptor-alpha
      (PPARalpha)/mitochondria pathway in response to acute oxidative stress in
      cultured cardiomyocytes. Cultured H9c2 rat embryonic cardioblasts were exposed to
      H2O2-induced acute oxidative stress in the presence or absence of metformin,
      compound C (AMPK inhibitor), GW6471 (PPARalpha inhibitor), or A-769662 (AMPK
      activator). Results showed that AMPK activation by metformin reverted oxidative
      stress-induced inactivation of AMPK and prevented oxidative stress-induced cell
      death. In addition, metformin attenuated reactive oxygen species generation and
      depolarization of the inner mitochondrial membrane. The antioxidative effects of
      metformin were associated with the prevention of mitochondrial DNA damage in
      cardiomyocytes. Coimmunoprecipitation studies revealed that metformin abolished
      oxidative stress-induced physical interactions between PPARalpha and cyclophilin
      D (CypD), and the abolishment of these interactions was associated with
      inhibition of permeability transition pore formation. The beneficial effects of
      metformin were not due to acetylation or phosphorylation of PPARalpha in response
      to oxidative stress. In conclusion, this study demonstrates that the protective
      effects of metformin-induced AMPK activation against oxidative stress converge on
      mitochondria and are mediated, at least in part, through the dissociation of
      PPARalpha-CypD interactions, independent of phosphorylation and acetylation of
      PPARalpha and CypD.

PMID- 25617360
TI  - Correction for Li et al., Arabidopsis ribosomal proteins control vacuole
      trafficking and developmental programs through the regulation of lipid
      metabolism.

PMID- 25617358
TI  - Measurement of shear stress-mediated intracellular calcium dynamics in human
      dermal lymphatic endothelial cells.
AB  - The shear stress applied to lymphatic endothelial cells (LEC) by lymph flow
      changes dramatically under normal conditions as well as in response to disease
      conditions and immune reactions. In general, LEC are known to regulate the
      contraction frequency and strength of lymphatic pumping in response to shear
      stress. Intracellular calcium concentration ([Ca(2+)]i) is an important factor
      that regulates lymphatic contraction characteristics. In this study, we measured
      changes in the [Ca(2+)]i under different shear stress levels and determined the
      source of this calcium signal. Briefly, human dermal LEC were cultured in custom
      made microchannels for 3 days before loading with 2 uM fura-2 AM, a ratiometric
      calcium dye to measure [Ca(2+)]i. Step changes in shear stress resulted in a
      rapid increase in [Ca(2+)]i followed by a gradual return to the basal level and
      sometimes below the initial baseline (45.2 +/- 2.2 nM). The [Ca(2+)]i reached a
      peak at 126.2 +/- 5.6 nM for 10 dyn/cm(2) stimulus, whereas the peak was only
      71.8 +/- 5.4 nM for 1 dyn/cm(2) stimulus, indicating that the calcium signal
      depends on the magnitude of shear stress. Removal of the extracellular calcium
      from the buffer or pharmocological blockade of calcium release-activated calcium
      (CRAC) channels significantly reduced the peak [Ca(2+)]i, demonstrating a role of
      extracellular calcium entry. Inhibition of endoplasmic reticulum (ER) calcium
      pumps showed the importance of intracellular calcium stores in the initiation of
      this signal. In conclusion, we demonstrated that the shear-mediated calcium
      signal is dependent on the magnitude of the shear and involves ER store calcium
      release and extracellular calcium entry.

PMID- 25617359
TI  - Strain and strain rate by speckle-tracking echocardiography correlate with
      pressure-volume loop-derived contractility indices in a rat model of athlete's
      heart.
AB  - Contractile function is considered to be precisely measurable only by invasive
      hemodynamics. We aimed to correlate strain values measured by speckle-tracking
      echocardiography (STE) with sensitive contractility parameters of pressure-volume
      (P-V) analysis in a rat model of exercise-induced left ventricular (LV)
      hypertrophy. LV hypertrophy was induced in rats by swim training and was compared
      with untrained controls. Echocardiography was performed using a 13-MHz linear
      transducer to obtain LV long- and short-axis recordings for STE analysis (GE
      EchoPAC). Global longitudinal (GLS) and circumferential strain (GCS) and
      longitudinal (LSr) and circumferential systolic strain rate (CSr) were measured.
      LV P-V analysis was performed using a pressure-conductance microcatheter, and
      load-independent contractility indices [slope of the end-systolic P-V
      relationship (ESPVR), preload recruitable stroke work (PRSW), and maximal dP/dt
      end-diastolic volume relationship (dP/dtmax-EDV)] were calculated. Trained rats
      had increased LV mass index (trained vs. control; 2.76 +/- 0.07 vs. 2.14 +/- 0.05
      g/kg, P < 0.001). P-V loop-derived contractility parameters were significantly
      improved in the trained group (ESPVR: 3.58 +/- 0.22 vs. 2.51 +/- 0.11 mmHg/MUl;
      PRSW: 131 +/- 4 vs. 104 +/- 2 mmHg, P < 0.01). Strain and strain rate parameters
      were also supernormal in trained rats (GLS: -18.8 +/- 0.3 vs. -15.8 +/- 0.4%;
      LSr: -5.0 +/- 0.2 vs. -4.1 +/- 0.1 Hz; GCS: -18.9 +/- 0.8 vs. -14.9 +/- 0.6%;
      CSr: -4.9 +/- 0.2 vs. -3.8 +/- 0.2 Hz, P < 0.01). ESPVR correlated with GLS (r = 
      0.71) and LSr (r = -0.53) and robustly with GCS (r = -0.83) and CSr (r = -0.75,
      all P < 0.05). PRSW was strongly related to GLS (r = -0.64) and LSr (r = -0.71,
      both P < 0.01). STE can be a feasible and useful method for animal experiments.
      In our rat model, strain and strain rate parameters closely reflected the
      improvement in intrinsic contractile function induced by exercise training.

PMID- 25617361
TI  - Fear of terror and inflammation ignite heart health decline.

PMID- 25617362
TI  - Correction for Li et al., Waking sleeping algal cells.

PMID- 25617363
TI  - Correction for Han et al., Structural basis for the auxin-induced transcriptional
      regulation by Aux/IAA17.

PMID- 25617364
TI  - Malaria parasite Pfs47 disrupts JNK signaling to escape mosquito immunity.

PMID- 25617366
TI  - Correction for Das et al., Structure of CrgA, a cell division structural and
      regulatory protein from Mycobacterium tuberculosis, in lipid bilayers.

PMID- 25617365
TI  - Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver
      kinase B1.
AB  - The inositol pyrophosphates, molecular messengers containing an energetic
      pyrophosphate bond, impact a wide range of biologic processes. They are generated
      primarily by a family of three inositol hexakisphosphate kinases (IP6Ks), the
      principal product of which is diphosphoinositol pentakisphosphate (IP7). We
      report that IP6K2, via IP7 synthesis, is a major mediator of cancer cell
      migration and tumor metastasis in cell culture and in intact mice. IP6K2 acts by
      enhancing cell-matrix adhesion and decreasing cell-cell adhesion. This action is
      mediated by IP7-elicited nuclear sequestration and inactivation of the tumor
      suppressor liver kinase B1 (LKB1). Accordingly, inhibitors of IP6K2 offer promise
      in cancer therapy. 

PMID- 25617368
TI  - Herman N. Eisen: Mentor to many.

PMID- 25617367
TI  - Effector Vgamma9Vdelta2 T cells dominate the human fetal gammadelta T-cell
      repertoire.
AB  - gammadelta T cells are unconventional T cells recognizing antigens via their
      gammadelta T-cell receptor (TCR) in a way that is fundamentally different from
      conventional alphabeta T cells. gammadelta T cells usually are divided into
      subsets according the type of Vgamma and/or Vdelta chain they express in their
      TCR. T cells expressing the TCR containing the gamma-chain variable region 9 and
      the delta-chain variable region 2 (Vgamma9Vdelta2 T cells) are the predominant
      gammadelta T-cell subset in human adult peripheral blood. The current thought is
      that this predominance is the result of the postnatal expansion of cells
      expressing particular complementary-determining region 3 (CDR3) in response to
      encounters with microbes, especially those generating phosphoantigens derived
      from the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid synthesis.
      However, here we show that, rather than requiring postnatal microbial exposure,
      Vgamma9Vdelta2 T cells are the predominant blood subset in the second-trimester
      fetus, whereas Vdelta1(+) and Vdelta3(+) gammadelta T cells are present only at
      low frequencies at this gestational time. Fetal blood Vgamma9Vdelta2 T cells are
      phosphoantigen responsive and display very limited diversity in the CDR3 of the
      Vgamma9 chain gene, where a germline-encoded sequence accounts for >50% of all
      sequences, in association with a prototypic CDR3delta2. Furthermore, these fetal
      blood Vgamma9Vdelta2 T cells are functionally preprogrammed (e.g., IFN-gamma and
      granzymes-A/K), with properties of rapidly activatable innatelike T cells. Thus,
      enrichment for phosphoantigen-responsive effector T cells has occurred within the
      fetus before postnatal microbial exposure. These various characteristics have
      been linked in the mouse to the action of selecting elements and would establish
      a much stronger parallel between human and murine gammadelta T cells than is
      usually articulated. 

PMID- 25617369
TI  - How many proteins does it take to gate hair cell mechanotransduction?

PMID- 25617370
TI  - Reply to Constantin-Teodosiu et al.: mice with genetic PDH activation are not
      protected from high-fat diet-induced muscle insulin resistance.

PMID- 25617371
TI  - Perpetual muscle PDH activation in PDH kinase knockout mice protects against high
      fat feeding-induced muscle insulin resistance.

PMID- 25617372
TI  - Reply to O'Neill et al. and O'Sullivan: Fertility reduction will help, but only
      in the long term.

PMID- 25617373
TI  - Plausible reductions in future population growth and implications for the
      environment.

PMID- 25617374
TI  - Population stabilization potential and its benefits underestimated.

PMID- 25617375
TI  - Methane emissions from natural gas infrastructure and use in the urban region of
      Boston, Massachusetts.
AB  - Methane emissions from natural gas delivery and end use must be quantified to
      evaluate the environmental impacts of natural gas and to develop and assess the
      efficacy of emission reduction strategies. We report natural gas emission rates
      for 1 y in the urban region of Boston, using a comprehensive atmospheric
      measurement and modeling framework. Continuous methane observations from four
      stations are combined with a high-resolution transport model to quantify the
      regional average emission flux, 18.5 +/- 3.7 (95% confidence interval) g CH4 ? m(
      2) ? y(-1). Simultaneous observations of atmospheric ethane, compared with the
      ethane-to-methane ratio in the pipeline gas delivered to the region, demonstrate
      that natural gas accounted for ~ 60-100% of methane emissions, depending on
      season. Using government statistics and geospatial data on natural gas use, we
      find the average fractional loss rate to the atmosphere from all downstream
      components of the natural gas system, including transmission, distribution, and
      end use, was 2.7 +/- 0.6% in the Boston urban region, with little seasonal
      variability. This fraction is notably higher than the 1.1% implied by the most
      closely comparable emission inventory.

PMID- 25617376
TI  - Alterations in expression of elastogenic and angiogenic genes by different
      conditions of mechanical ventilation in newborn rat lung.
AB  - Mechanical ventilation is an important risk factor for development of
      bronchopulmonary dysplasia. Here we investigated the effects of different tidal
      volumes (VT) and duration of ventilation on expression of genes involved in
      alveolarization [tropoelastin (Eln), lysyloxidase-like 1 (Loxl1), fibulin5
      (Fbln5), and tenascin-C (Tnc)] and angiogenesis [platelet derived growth factors
      (Pdgf) and vascular endothelial growth factors (Vegf) and their receptors] in 8
      day-old rats. First, pups were ventilated for 8 h with low (LVT: 3.5 ml/kg),
      moderate (MVT: 8.5 ml/kg), or high (HVT: 25 ml/kg) tidal volumes. LVT and MVT
      decreased Tnc expression, whereas HVT increased expression of all three
      elastogenic genes and Tnc. PDGF alpha-receptor mRNA was increased in all
      ventilation groups, while Pdgfb expression was decreased after MVT and HVT
      ventilation. Only HVT ventilation upregulated Vegf expression. Independent of VT,
      ventilation upregulated Vegfr1 expression, while MVT and HVT downregulated Vegfr2
      expression. Next, we evaluated duration (0-24 h) of MVT ventilation on gene
      expression. Although expression of all elastogenic genes peaked at 12 h of
      ventilation, only Fbln5 was negatively affected at 24 h. Tnc expression decreased
      with duration of ventilation. Changes in expression of Pdgfr and Vegfr were
      maximal at 8 h of ventilation. Disturbed elastin fiber deposition and decrease in
      small vessel density was only observed after 24 h. Thus, an imbalance between
      Fbln5 and Eln expression may trigger dysregulated elastin fiber deposition during
      the first 24 h of mechanical ventilation. Furthermore, ventilation-induced
      alterations in Pdgf and Vegf receptor expression are tidal volume dependent and
      may affect pulmonary vessel formation.

PMID- 25617377
TI  - Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal
      simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to
      lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN).
      Simvastatin has been shown to prevent the development of pulmonary hypertension
      (PH) in experimental models of PH. We, therefore, hypothesized that antenatal
      simvastatin would attenuate PPHN in nitrofen-induced CDH in rats. The efficacy of
      antenatal simvastatin was compared with antenatal sildenafil, which has already
      been shown to improve pathological features of PPHN in nitrofen-induced CDH. On
      embryonic day (E) 9.5, nitrofen or vehicle was administered to pregnant Sprague
      Dawley rats. On E11, nitrofen-treated rats were randomly assigned to antenatal
      simvastatin (20 mg.kg(-1).day(-1) orally), antenatal sildenafil (100 mg.kg(
      1).day(-1) orally), or placebo administration from E11 to E21. On E21, fetuses
      were delivered by cesarean section, killed, and checked for left-sided CDH. Lung
      tissue was then harvested for further pathobiological evaluation. In nitrofen
      induced CDH, simvastatin failed to reduce the incidence of nitrofen-induced CDH
      in the offspring and to increase the body weight, but improved the lung-to-body
      weight ratio and lung parenchyma structure. Antenatal simvastatin restored the
      pulmonary vessel density and external diameter, and reduced the pulmonary
      arteriolar remodeling compared with nitrofen-induced CDH. This was associated
      with decreased lung expression of endothelin precursor, endothelin type A and B
      receptors, endothelial and inducible nitric oxide synthase, together with
      restored lung activation of apoptotic processes mainly in the epithelium.
      Antenatal simvastatin presented similar effects as antenatal therapy with
      sildenafil on nitrofen-induced CDH. Antenatal simvastatin improves pathological
      features of lung hypoplasia and PPHN in experimental nitrofen-induced CDH. 

PMID- 25617378
TI  - Inflammatory impact of IFN-gamma in CD8+ T cell-mediated lung injury is mediated
      by both Stat1-dependent and -independent pathways.
AB  - Influenza infection results in considerable pulmonary pathology, a significant
      component of which is mediated by CD8(+) T cell effector functions. To isolate
      the specific contribution of CD8(+) T cells to lung immunopathology, we utilized
      a nonviral murine model in which alveolar epithelial cells express an influenza
      antigen and injury is initiated by adoptive transfer of influenza-specific CD8(+)
      T cells. We report that IFN-gamma production by adoptively transferred influenza
      specific CD8(+) T cells is a significant contributor to acute lung injury
      following influenza antigen recognition, in isolation from its impact on viral
      clearance. CD8(+) T cell production of IFN-gamma enhanced lung epithelial cell
      expression of chemokines and the subsequent recruitment of inflammatory cells
      into the airways. Surprisingly, Stat1 deficiency in the adoptive-transfer
      recipients exacerbated the lung injury that was mediated by the transferred
      influenza-specific CD8(+) T cells but was still dependent on IFN-gamma production
      by these cells. Loss of Stat1 resulted in sustained activation of Stat3
      signaling, dysregulated chemokine expression, and increased infiltration of the
      airways by inflammatory cells. Taken together, these data identify important
      roles for IFN-gamma signaling and Stat1-independent IFN-gamma signaling in
      regulating CD8(+) T cell-mediated acute lung injury. This is the first study to
      demonstrate an anti-inflammatory effect of Stat1 on CD8(+) T cell-mediated lung
      immunopathology without the complication of differences in viral load.

PMID- 25617379
TI  - Rapamycin Normalizes Serum Leptin by Alleviating Obesity and Reducing Leptin
      Synthesis in Aged Rats.
AB  - This investigation examines whether a low intermittent dose of rapamycin will
      avoid the hyperlipidemia and diabetes-like syndrome associated with rapamycin
      while still decreasing body weight and adiposity in aged obese rats. Furthermore,
      we examined if the rapamycin-mediated decrease in serum leptin was a reflection
      of decreased adiposity, diminished leptin synthesis, or both. To these ends,
      rapamycin (1mg/kg) was administered three times a week to 3 and 24-month old
      rats. Body weight, food intake, body composition, mTORC1 signaling, markers of
      metabolism, as well as serum leptin levels and leptin synthesis in adipose tissue
      were examined and compared to that following a central infusion of rapamycin. Our
      data suggest that the dosing schedule of rapamycin acts on peripheral targets to
      inhibit mTORC1 signaling, preferentially reducing adiposity and sparing lean mass
      in an aged model of obesity resulting in favorable outcomes on blood
      triglycerides, increasing lean/fat ratio, and normalizing elevated serum leptin
      with age. The initial mechanism underlying the rapamycin responses appears to
      have a peripheral action and not central. The peripheral rapamycin responses may
      communicate an excessive nutrients signal to the hypothalamus that triggers an
      anorexic response to reduce food consumption. This coupled with potential
      peripheral mechanism serves to decrease adiposity and synthesis of leptin.

PMID- 25617381
TI  - Bacterial pneumonia in older people.

PMID- 25617380
TI  - Rapamycin Versus Intermittent Feeding: Dissociable Effects on Physiological and
      Behavioral Outcomes When Initiated Early and Late in Life.
AB  - Rapamycin, an inhibitor of the mammalian target of rapamycin pathway, has been
      shown to increase mammalian life span; less is known concerning its effect on
      healthspan. The primary aim of this study was to examine rapamycin's role in the
      alteration of several physiological and behavioral outcomes compared with the
      healthspan-inducing effects of intermittent feeding (IF), another life-span
      enhancing intervention. Male Fisher 344 * Brown Norway rats (6 and 25 months of
      age) were treated with rapamycin or IF for 5 weeks. IF and rapamycin reduced food
      consumption and body weight. Rapamycin increased relative lean mass and decreased
      fat mass. IF failed to alter fat mass but lowered relative lean mass.
      Behaviorally, rapamycin resulted in high activity levels in old animals, IF
      increased levels of "anxiety" for both ages, and grip strength was not
      significantly altered by either treatment. Rapamycin, not IF, decreased
      circulating leptin in older animals to the level of young animals. Glucose levels
      were unchanged with age or treatment. Hypothalamic AMPK and pAMPK levels
      decreased in both older treated groups. This pattern of results suggests that
      rapamycin has more selective and healthspan-inducing effects when initiated late
      in life.

PMID- 25617382
TI  - An evaluation of demographic factors affecting performance in a paediatric
      membership multiple-choice examination.
AB  - OBJECTIVE: To determine if demographic factors are associated with outcome in a
      multiple-choice, electronically marked paediatric postgraduate examination.
      METHOD: Retrospective analysis of pass rates of UK trainees sitting Membership of
      the Royal College of Paediatrics and Child Health (MRCPCH) part 1B from 2007 to
      2011. Data collected by the RCPCH from examination candidates were analysed to
      assess the effects of gender, age, and country and university of medical
      qualification on examination outcome. RESULTS: At first attempt at MRCPCH part
      1B, the overall pass rate from 2007 to 2011 was 843/2056 (41.0%). In univariate
      analysis, passing the examination was associated with being a UK graduate
      (649/1376 (47.2%)) compared with being an international medical graduate (130/520
      (25.0%)) (OR 2.68 (95% CI 2.14 to 3.36), p<0.001). There was strong evidence that
      the proportion of candidates passing the examination differed for graduates of
      the 19 different UK medical schools (Fisher's exact test p<0.001). In
      multivariate logistic regression analysis, after adjustment for age, sex and
      whether the part 1A examination was taken concurrently, being a UK graduate was
      still strongly associated with passing the examination (OR 3.17 (95% CI 2.41 to
      4.17), p<0.001). UK graduates performed best at 26-27 years of age (52.4% pass
      rate), whereas overseas graduates performed best at >=38 years of age (50.8% pass
      rate). CONCLUSIONS: MRCPCH part 1B outcome was related to place of primary
      medical qualification, with a significantly lower pass rate for international
      medical graduates compared with UK graduates, as well as significant variation in
      examination outcome between graduates from different UK medical schools. These
      data may be used to guide new initiatives to improve support and education for
      these trainees and to inform development of undergraduate curricula and help
      trainees prepare more successfully for postgraduate examinations.

PMID- 25617383
TI  - Postpartum headache.

PMID- 25617385
TI  - Utility of reflexive gomori methenamine silver and Acid-fast bacillus staining on
      bronchoalveolar lavage specimens.
AB  - OBJECTIVE: Reflexive testing of bronchoalveolar lavage (BAL) specimens with
      Gomori methenamine silver (GMS) and acid-fast bacillus (AFB) stains is not
      routinely performed by most institutions. Instead, these stains are usually
      ordered to evaluate for the presence of fungal elements and/or acid-fast
      organisms if initial histopathologic assessment suggests the presence of these
      pathogens. Our institution, however, performs these stains on all BAL specimens.
      Thus, we sought to determine whether this practice was cost effective,
      considering the turnaround time and diagnostic efficacy of these tests. METHODS:
      We retrospectively reviewed 488 BAL specimens performed at two military
      healthcare institutions over a 2-year period and performed a cost analysis with
      review of the impact on turnaround time. RESULTS: Of the 488 cases, we identified
      only 3 (~0.6%) with infections by acid-fast or fungal organisms, at an estimated
      total cost of $12,151.20 and an average delay of 3.0 to 3.5 hours for slide
      preparation. CONCLUSION: Our results suggest that in a largely young and healthy
      population such as ours, it may be more feasible to perform these stains on BAL
      specimens on a case-by-case basis rather than automatically on every specimen, to
      control costs and enhance productivity.

PMID- 25617386
TI  - beta-Globin Mutations in Egyptian Patients With beta-Thalassemia.
AB  - beta-thalassemia is a common hereditary disorder, particularly in Middle Eastern
      countries. More than 200 mutations in the beta globin gene have been reported;
      most are point mutations in functionally important regions (HBB; OMIM #141900)).
      The spectrum of mutations varies significantly between different geographical
      regions; only a few common mutations of beta-globin cause beta-thalassemia in
      each population. The aim of this study was to determine the spectrum of mutations
      that cause beta-thalassemia in the North Coast of Egypt and to investigate their
      correlation with the phenotypic severity of beta-thalassemia. We carried out our
      study with a total of 47 Egyptian patients (25 male and 22 female) confirmed to
      have beta-thalassemia. Evaluation of beta-thalassemia mutations revealed the
      presence of 10 beta-globin mutations. The most frequently encountered mutations
      were intronic: IVS 1.6 [T>C] (27.66%) and IVS 1.110 [G>A] (22.35%), followed by
      IVS 2.848 [C>A], IVS 1.1 (G>A), and IVS 2.745 [C>G]. We observed the exonic and
      promoter mutations less frequently. A homozygous mutation was found in 24
      patients (51%) and compound heterozygous mutations were found in 13 patients
      (28%). However, in 9 patients (19%), we identified only 1 mutation. In 1 patient
      (2%), we detected no mutation. The detection rate of the method that we used in
      our population was 88% (83 of the tested 94 alleles). The results we obtained did
      not reveal any correlation between genotype and phenotype among patients with
      beta-thalassemia. 

PMID- 25617387
TI  - The T-SPOT.TB Test for Diagnosis of Breast Tuberculosis.
AB  - OBJECTIVE: To assess the diagnostic value of the T-SPOT.TB test in cases of
      breast turberculosis (BTB) in China. METHODS: We enrolled 13 female patients with
      primary BTB as the BTB test group and 10 healthy volunteers as the control group.
      The 2 groups underwent T-SPOT.TB tests and tuberculin skin tests (TSTs) before
      receiving a core-needle biopsy or excision biopsy. We then collected and analyzed
      T-SPOT.TB and TST data. RESULTS: The sensitivity of the T-SPOT.TB test for
      detection of BTB (84.6%) was significantly greater than that of TST (53.8%) (P
      <.05); the specificity of each test (80.0% and 60.0%, respectively) for BTB was
      not significantly different (P >.05). CONCLUSION: The T-SPOT.TB test could be a
      useful adjunct to current tests for diagnosis of BTB and could be used for early
      diagnosis of this condition.

PMID- 25617388
TI  - Heritability of IL-1A Gene Promoter Polymorphism in Patients With Coronary Artery
      Disease: A Trio-Family Study.
AB  - OBJECTIVE: To investigate the potential role of IL-1A gene variations in
      pathogenesis of coronary artery disease (CAD) with familial history. MATERIALS
      AND METHODS: We investigated the IL-1A-889C>T polymorphism in 335 patients with
      CAD and 335 healthy individuals for case-control association analysis. In this
      study, we also investigated the heritability of the susceptible allele from 130
      trio families with CAD-affected offspring. We performed genotyping using the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. RESULTS: The IL-1A-889 C/T polymorphism was significantly associated with
      CAD in patients compared with healthy controls. The minor allele T at -889 was
      more prevalent in cases vs controls. The results of a transmission disequilibrium
      test revealed a significant association between the IL-1A-889 polymorphism and
      CAD. The mutant genotype CT+TT was significantly associated with high levels of
      high-sensitivity C-reactive protein (CRP) and other relative markers from
      patients with CAD. CONCLUSION: For the first time in the literature, to our
      knowledge, we demonstrate a significant association of the IL-1A-889 functional
      polymorphism with CAD.

PMID- 25617389
TI  - Resolving Transferrin Isoforms via Agarose Gel Electrophoresis.
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) leaks may present as rhinorrhea or otorrhea
      and can lead to life-threatening complications if not detected. The usefulness of
      the morpholinopropanesulfonic acid (MOPS)-histidine buffer in detecting beta2
      transferrin, which is only found in the cerebrospinal fluid, was compared with
      the standard barbital buffer. METHODS: We evaluated 20 aural or nasal patient
      specimens submitted for CSF testing via agarose electrophoresis with barbital and
      MOPS-histidine buffers. RESULTS: The MOPS-histidine and barbital buffers revealed
      5 transferrin bands and 2 transferrin bands with CSF, respectively. Seventeen of
      20 patient specimens had concordant results. The 3 discrepant specimens initially
      tested negative with the barbital buffer and positive with the MOPS-histidine
      buffer. Two of the 3 patient specimens later tested positive with the barbital
      buffer when a new specimen was submitted. CONCLUSION: Agarose electrophoresis
      with the MOPS-histidine buffer increases the resolution of transferrin isoforms.

PMID- 25617390
TI  - Sterility Testing of Stem Cell Products by Broad-Range Bacterial 16S Ribosomal
      DNA Polymerase Chain Reaction.
AB  - OBJECTIVE: To evaluate broad-range 16S ribosomal DNA (rDNA) polymerase chain
      reaction (PCR) as a rapid screening tool to detect bacterial contamination of
      stem-cell products. METHODS: We performed the evaluation using whole blood spiked
      with serially diluted bacterial-type strains. Detection sensitivity was defined
      as the bacterial concentration for which all replicates were positive at each
      concentration (100% detection). We tested the sterility of 29 bags of autologous
      peripheral blood stem cell (PBSC) products harvested at our facility using the
      16S rDNA PCR method. RESULTS: The detection sensitivity of 16S rDNA PCR in spiked
      whole blood was 101 to 102 colony-forming units (CFU) per mL, depending on the
      bacterial strain. We detected no amplified 16S rDNA among the PBSCs we used in
      this study. The BacT/ALERT automated bacterial culture system that we used also
      showed no positive signals in any of the PBSCs tested. CONCLUSIONS: Our data
      indicate that bacterial 16S rDNA PCR is a useful alternative for rapid sterility
      testing, not only for blood products used in transfusion medicine but also for
      stem-cell products used in regenerative medicine.

PMID- 25617391
TI  - Malaria parasitemia in apparently healthy blood donors in north-central Nigeria.
AB  - OBJECTIVE: To determine the prevalence of transmissible malaria in apparently
      healthy blood donors in the city of Jos in north-central Nigeria. METHODS: We
      collected blood specimens from individuals who had passed the screening criteria
      for blood donation. We created thin and thick blood films using the blood film
      template provided by the World Health Organization (WHO). The films were allowed
      to air dry; then, we stained them using a 3% Giemsa solution and examined them
      microscopically. In specimens that tested positive the malaria species was
      identified. RESULTS: The highest prevalence of malaria was in donors aged between
      31 and 40 years (65.1%), whereas the lowest prevalence was in donors aged 20
      years or younger (25.0%). Plasmodium falciparum was the predominant species
      (98.0%); the least prevalent was Plasmodium malariae (2.0%). In male donors the
      prevalence of malaria parasitemia was 62.0%; the prevalence in female donors was
      62.5%. Among paid donors the malaria parasitemia rate was 82.3%, compared with
      22.4% in volunteer donors. Donors who reported their occupation as businessperson
      (individual who engages in commercial trade, mostly outdoors in a market
      environment) had the highest prevalence, at 94.3%; students had the lowest
      prevalence, at 31.9%. CONCLUSION: A high percentage of blood donors in Jos,
      Nigeria, actually harbor malaria, which is cause for concern and more careful
      donor screening by healthcare professionals in that region is warranted.

PMID- 25617392
TI  - Specimen recentrifugation and elevated troponin I levels.
AB  - OBJECTIVE: To compare troponin I levels in plasma before and after specimen
      recentrifugation. METHODS: Over a period of 24 consecutive days, we recentrifuged
      189 plasma specimens in which the troponin I level was higher than the positivity
      cut off (60 ng/L) and then remeasured the troponin I. RESULTS: Two-tailed
      Wilcoxon matched-pairs test results identified a statistically significant
      difference between troponin I concentrations before and after recentrifugation (P
      <.01). For 94 specimens close to the cut-off value (below the 50th percentile
      among the overall sample of 189 specimens), Passing-Bablok regression analysis
      showed a median reduction of 10 ng/L (95% confidence interval, -37.5 ng/L - -10.0
      ng/L) in the concentrations of troponin I after recentrifugation. CONCLUSION:
      Specimen recentrifugation is followed by a reduction in troponin I concentrations
      in specimens with elevated cardiac troponin I, posing a risk for
      misclassification of patients. Moreover, this practice gives rise to unnecessary
      prolongation of turnaround time.

PMID- 25617393
TI  - Specimen Age Stability for Human Papilloma Virus DNA Testing Using BD SurePath.
AB  - BACKGROUND: Currently, the BD SurePath liquid-based Papanicolaou (Pap) test is
      approved by the U.S. Food and Drug Administration (FDA) only for Pap testing;
      however, these specimens are widely used for human papilloma virus (HPV) testing.
      METHODS: We retested, at 21 days after the collection date, 50 BD SurePath
      specimens that had initially tested positive for high-risk HPV using the Roche
      Cobas 4800 assay to compare repeat results of aged specimens to original results
      and evaluate false-negative results. RESULTS: Of 50 specimens that initially
      tested positive for HPV DNA with the Roche Cobas 4800 assay (average, 7 days), 8
      tested negative when retested at 21 days after the collection date (false
      negative rate, 16.0%). CONCLUSION: Aged BD SurePath-preserved Pap test specimens
      older than 21 days from collection date may produce false-negative HPV DNA
      testing results when testing with assays such as Roche Cobas 4800, most likely
      due to degradation of DNA. Guidelines are needed to limit specimen age to less
      than 2 weeks to prevent false-negative test results and to improve diagnostic
      accuracy and patient care.

PMID- 25617394
TI  - Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody
      exacerbated by epstein-barr virus.
AB  - Most cases of autoimmune hemolytic anemia (AIHA) are caused by the production of
      an autoantibody that targets determinants on red blood cells (RBCs). This
      autoantibody can be immunoglobulin (Ig) G, IgM, or IgA. Some autoantibodies react
      optimally at 0 degrees  to 4 degrees C (ie, cold agglutinin) and usually are
      clinically insignificant. High-titer cold agglutinins are associated with IgM
      autoantibody and complement fixation induced by infectious agents, including the
      Epstein-Barr virus (EBV). This case report describes a 31-year-old man who had
      jaundice, a hemoglobin of 6.0 gdL, and was diagnosed with a hemolytic crisis of
      AIHA. He received a total of 11 RBC transfusions during a 15-hour period without
      sustained response and later died. The direct antiglobulin test results for this
      patient were positive, whereas the cold-agglutinin-testing results were negative.
      We detected EBV DNA in blood via polymerase chain reaction (PCR). We report a
      rare case of AIHA associated with an IgG autoantibody and exacerbated by EBV
      infection, causing a fatal hemolytic anemia. 

PMID- 25617395
TI  - A 5-hour-old male neonate with cyanosis.
AB  - Methemoglobin (MetHb) is a form of hemoglobin in which heme iron is oxidized and
      unable to bind oxygen; its normal basal production is counteracted by an
      efficient MetHb-reduction pathway. The causes of methemoglobinemia are classified
      as congenital or acquired. Shortly after his birth, the 5-hour-old male Caucasian
      neonate, whose case we present herein, developed central cyanosis that was
      unresponsive to supplemental oxygen. Oxygen saturation as determined via pulse
      oximetry was normal. In contrast, blood gas testing by multiwave CO-oximetry
      indicated decreased fractional oxyhemoglobin and an elevated MetHb fraction. The
      patient was subsequently diagnosed with a congenital cytochrome b5 reductase
      deficiency. This case emphasizes causes of methemoglobinemia and differences
      among analytical methods used to measure oxygen status when MetHb is present. 

PMID- 25617396
TI  - Normal karyotype in a case of acute myeloid leukemia with monocytic
      differentiation and hemophagocytosis by leukemic blasts.
AB  - We report the case of a 39-year-old woman with acute myeloid leukemia (AML) with
      monocytic differentiation showing hemophagocytosis by leukemic blasts. This
      phenomenon is known to be associated with certain chromosomal changes, including
      t(8;16), der(8), inv(8), and t(16;21); however, in this case, the patient had a
      normal female karyotype. To our knowledge, this is the first published case of
      normal karyotype AML with hemophagocytosis by leukemic blasts. 

PMID- 25617397
TI  - Postpartum cryptococcal pulmonary lesion incidentally discovered during a
      pulmonary-embolism evaluation of a 28-year-old caucasian woman.
AB  - We report a case of localized pulmonary cryptococcal infection in a 28-year-old
      Caucasian woman who was 1 month postpartum at the time of her arrival at the
      hospital. The patient reported right-side chest pain; on further work up, she was
      found to have an incidental pulmonary lesion of the left lower lung lobe.
      Surgical pathology examination and microbiology studies revealed localized
      cryptococcal infection. Cases of cryptococcal pneumonia in pregnant women and in
      the postpartum period have been described in the literature. However,
      cryptococcal infections are usually associated with various immunocompromised
      states, including human immunodeficiency virus (HIV) infection. Because pregnancy
      is associated with physiological immunosuppression, cryptococcal pneumonia should
      be considered in pregnant women, or women in the postpartum period, who have
      respiratory symptoms. 

PMID- 25617398
TI  - Decreasing preoperative autologous blood donation: collaboration between a
      hospital and a blood center to prompt change in physician ordering behavior.
AB  - OBJECTIVE: To describe the collaborative efforts of a large healthcare
      institution and its local blood center in reducing preoperative autologous blood
      donation (PABD). METHODS: Through an educational letter-based campaign, we
      contacted physicians who historically had ordered PABD units. Follow-up
      educational efforts occurred at departmental and individual meetings. RESULTS:
      Our educational campaign to reduce PABD achieved complete elimination of PABD
      orders and the resultant waste of PABD units within 3 years of the start of the
      program. These changes were sustained for at least 2 subsequent years without the
      need for additional educational efforts. CONCLUSION: Targeted educational efforts
      directed at practitioners of PABD were successful in significantly decreasing the
      use and waste of PABD at the health care institution we studied and may yield the
      same results in comparable institutions.

PMID- 25617399
TI  - Depression and Frailty in Late Life: Evidence for a Common Vulnerability.
AB  - OBJECTIVES: The study purpose is to estimate the correlation between depression
      and competing models of frailty, and to determine to what degree the comorbidity
      of these syndromes is determined by shared symptomology. METHODS: Data come from
      the 2010 Health and Retirement Study. Analysis was limited to community-dwelling
      participants 65 and older (N = 3,453). Depressive symptoms were indexed by the 8
      item Centers for Epidemiologic Studies Depression (CESD) scale. Frailty was
      indexed by 3 alternative conceptual models: (a) biological syndrome, (b) frailty
      index, and (c) functional domains. Confirmatory factor analysis (CFA) was used to
      estimate the correlation between depression and each model of frailty. RESULTS:
      Each of the 3 frailty latent factors was significantly correlated with
      depression: biological syndrome (rho = .68, p < .01), functional domains (rho =
      .70, p < .01), and frailty index (rho = .61, p < .01). Substantial correlation
      remained when accounting for shared symptoms between depression and the
      biological syndrome (rho = .45) and frailty index (rho = .56) models. DISCUSSION:
      Results indicate that the correlation of frailty and depression in late life is
      substantial. The association between the two constructs cannot be fully explained
      by symptom overlap, suggesting that psychological vulnerability may be an
      important component of frailty.

PMID- 25617400
TI  - Self-Rated Health, Interviewer-Rated Health, and Their Predictive Powers on
      Mortality in Old Age.
AB  - OBJECTIVES: This study examines the potential use of interviewer-rated health
      (IRH) as a complementary measure of self-rated health (SRH) through a systematic
      comparison of their components and mortality-predictive powers in the Chinese
      elderly population. METHODS: This study used a nationwide dataset with more than
      12,000 adults aged 65 or older drawn from the 2005 and 2008 waves of the Chinese
      Longitudinal Health Longevity Survey (CLHLS). RESULTS: Disability, cognitive
      function, chronic disease conditions, psychological well-being, and health
      behaviors influenced both the SRH and IRH of Chinese older adults; these factors,
      especially disabilities, explained a large portion of the association between SRH
      and mortality. However, the impact of these factors on the association between
      IRH and mortality was limited. Furthermore, when both SRH and IRH were included
      in the analytical models, the association between SRH and mortality disappeared,
      while the association between IRH and mortality still persisted. DISCUSSION:
      Although there is some difference between IRH and SRH, IRH captures similar
      health information as SRH and is strongly predictive of mortality independent of
      SRH; thus, IRH could be a good supplementary measurement for well-adopted SRH.

PMID- 25617401
TI  - Relocation and Social Support Among Older Adults in Rural China.
AB  - OBJECTIVES: China's economic reforms have led to millions of citizens being
      relocated to support infrastructure development, reduce poverty, and address
      ecological, disaster-related and other concerns. This study expands on previous
      research on the implications of relocation in China by examining the impact of
      rural elders' relocation on the perceived availability of emotional,
      instrumental, and financial support. METHODS: Data were drawn from the Ankang
      Study of Aging and Health conducted with a representative sample of 1,062 rural
      residents aged 60 and over living in Ankang, China. Two-stage probit and least
      squares regression models assessed the impact of relocation on familial and
      nonfamilial emotional, instrumental, and financial support. RESULTS: Relocation
      was negatively associated with the number of social support resources that older
      adults perceived as being available. Although this was the case with regard to
      both familial and nonfamilial support, it was particularly evident with regard to
      family support and, within families, with regard to instrumental rather than
      financial or emotional support. DISCUSSION: Relocation has negative implications
      for the number of social support resources perceived to be available by older
      adults in rural China. China will need to come to terms with how to provide for
      the instrumental support needs of an aging society.

PMID- 25617402
TI  - Pre-existing lumbar spine diagnosis as a predictor of outcomes in National
      Football League athletes.
AB  - BACKGROUND: It is currently unknown how pre-existing lumbar spine conditions may
      affect the medical evaluation, draft status, and subsequent career performance of
      National Football League (NFL) players. PURPOSE: To determine if a pre-existing
      lumbar diagnosis affects a player's draft status or his performance and longevity
      in the NFL. STUDY DESIGN: Cohort study; Level 3. METHODS: The investigators
      evaluated the written medical evaluations and imaging reports of prospective NFL
      players from a single franchise during the NFL Scouting Combine from 2003 to
      2011. Players with a reported lumbar spine diagnosis and with appropriate imaging
      were included in this study. Athletes were then matched to control draftees
      without a lumbar spine diagnosis by age, position, year, and round drafted.
      Career statistics and performance scores were calculated. RESULTS: Of a total of
      2965 athletes evaluated, 414 were identified as having a pre-existing lumbar
      spine diagnosis. Players without a lumbar spine diagnosis were more likely to be
      drafted than were those with a diagnosis (80.2% vs. 61.1%, respectively, P <
      .001). Drafted athletes with pre-existing lumbar spine injuries had a decrease in
      the number of years played compared with the matched control group (4.0 vs. 4.3
      years, respectively, P = .001), games played (46.5 vs. 50.8, respectively, P =
      .0001), and games started (28.1 vs. 30.6, respectively, P = .02) but not
      performance score (1.4 vs. 1.8, respectively, P = .13). Compared with controls,
      players were less likely to be drafted if they had been diagnosed with
      spondylosis (62.37% vs. 78.55%), a lumbar herniated disc (60.27% vs. 78.43%), or
      spondylolysis with or without spondylolisthesis (64.44% vs. 78.15%) (P < .001 for
      all), but there was no appreciable effect on career performance; however, the
      diagnosis of spondylolysis was associated with a decrease in career longevity (P
      < .05). Notably, 2 athletes who had undergone posterior lateral lumbar fusion
      were drafted. One played in 125 games, and the other is still active and has
      played in 108 games. CONCLUSION: The data in this study suggest that athletes
      with pre-existing lumbar spine conditions were less likely to be drafted and that
      the diagnosis is associated with a decrease in career longevity but not
      performance. Players with lumbar fusion have achieved successful careers in the
      NFL.

PMID- 25617403
TI  - Does obesity affect outcomes in hip arthroscopy? A matched-pair controlled study
      with minimum 2-year follow-up.
AB  - BACKGROUND: Hip arthroscopy has gained popularity over the past decade, and its
      indications have broadened as newer techniques have been developed. However,
      there has been a paucity of literature evaluating the outcomes of hip arthroscopy
      in obese patients. PURPOSE: To compare 2-year clinical outcomes of obese patients
      undergoing primary hip arthroscopy with matched nonobese controls. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: From February 2008 to February 2012,
      data were collected prospectively on all obese patients undergoing primary hip
      arthroscopy. A matched-pair nonobese control group was selected at a 1:2 ratio.
      All patients were assessed pre- and postoperatively with 4 patient-reported
      outcome (PRO) measures: the modified Harris Hip Score, Non-Arthritic Hip Score,
      Hip Outcome Score-Activities of Daily Living, and Hip Outcome Score-Sport
      Specific Subscale. Pain was estimated on the visual analog scale, and
      satisfaction was measured on a scale from 0 to 10. RESULTS: Sixty-two hips (62
      patients) were included in the obese group and 124 hips (124 patients) in the
      control group. At preoperative baseline, the obese group had significantly lower
      PRO scores when compared with the control group. Both groups demonstrated
      statistically significant postoperative improvement in all scores (P < .05).
      Absolute scores were significantly lower in the obese group for all PRO measures,
      pre- and postoperatively. However, the improvement (delta) in PRO scores from pre
      to postoperative time was not significantly different between groups. The rate
      of conversion to total hip arthroplasty, the rate of revision, and the
      complication rate were not significantly different between the 2 groups; however,
      rates of conversion to total hip arthroplasty and revision tended to be twice as
      high in the obese patients, but the study was not powered for these 2 outcomes.
      CONCLUSION: Overall, obese patients had lower absolute PRO scores preoperatively
      and at 2-year follow-up. Both obese and nonobese patients demonstrated
      significant improvement in all PRO scores, and the change in scores were similar
      between groups. These results indicate that while obese patients may not have
      similar absolute scores after hip arthroscopy, they may show similar gains in
      improvement when compared with baseline. Hip arthroscopy appears to be a viable
      treatment option in the obese patient as long as expectations are adjusted
      accordingly.

PMID- 25617404
TI  - Carotid artery dissection treated with stenting after anticoagulation failure.

PMID- 25617405
TI  - Recurrent amaurosis fugax and hemichorea: limb-shaking TIA.

PMID- 25617406
TI  - An unusual cause of seizures.

PMID- 25617407
TI  - Down Under: confessions of a vagrant registrar.

PMID- 25617408
TI  - A Bayesian model for the analysis of transgenerational epigenetic variation.
AB  - Epigenetics has become one of the major areas of biological research. However,
      the degree of phenotypic variability that is explained by epigenetic processes
      still remains unclear. From a quantitative genetics perspective, the estimation
      of variance components is achieved by means of the information provided by the
      resemblance between relatives. In a previous study, this resemblance was
      described as a function of the epigenetic variance component and a reset
      coefficient that indicates the rate of dissipation of epigenetic marks across
      generations. Given these assumptions, we propose a Bayesian mixed model
      methodology that allows the estimation of epigenetic variance from a genealogical
      and phenotypic database. The methodology is based on the development of a T:
      matrix of epigenetic relationships that depends on the reset coefficient. In
      addition, we present a simple procedure for the calculation of the inverse of
      this matrix ( T-1: ) and a Gibbs sampler algorithm that obtains posterior
      estimates of all the unknowns in the model. The new procedure was used with two
      simulated data sets and with a beef cattle database. In the simulated
      populations, the results of the analysis provided marginal posterior
      distributions that included the population parameters in the regions of highest
      posterior density. In the case of the beef cattle dataset, the posterior estimate
      of transgenerational epigenetic variability was very low and a model comparison
      test indicated that a model that did not included it was the most plausible. 

PMID- 25617409
TI  - Identification of eQTLs for hepatic Xbp1s and Socs3 gene expression in mice fed a
      high-fat, high-caloric diet.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent form of human
      hepatic disease and feeding mice a high-fat, high-caloric (HFHC) diet is a
      standard model of NAFLD. To better understand the genetic basis of NAFLD, we
      conducted an expression quantitative trait locus (eQTL) analysis of mice fed a
      HFHC diet. Two-hundred sixty-five (A/J * C57BL/6J) F2 male mice were fed a HFHC
      diet for 8 wk. eQTL analysis was utilized to identify genomic regions that
      regulate hepatic gene expression of Xbp1s and Socs3. We identified two
      overlapping loci for Xbp1s and Socs3 on Chr 1 (164.0-185.4 Mb and 174.4-190.5 Mb,
      respectively) and Chr 11 (41.1-73.1 Mb and 44.0-68.6 Mb, respectively), and an
      additional locus for Socs3 on Chr 12 (109.9-117.4 Mb). C57BL/6J-Chr 11(A/J)/ NaJ
      mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3
      gene expression (P < 0.05), whereas C57BL/6J-Chr 1(A/J)/ NaJ mice retained the
      C57BL/6J phenotype. In addition, we replicated the eQTLs on Chr 1 and Chr 12 (LOD
      scores >=3.5) using mice from the BXD murine reference panel challenged with CCl4
      to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs
      for Xbp1 and Socs3 on Chr 1 and Chr 11, and consomic mice confirmed that
      replacing the C57BL/6J Chr 11 with the A/J Chr 11 resulted in an A/J phenotype
      for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs
      will lead to a better understanding of the genetic factors responsible for NAFLD
      and potentially other hepatic diseases. 

PMID- 25617410
TI  - Phylogeny, biogeography and ecological diversification of Sarcocornia
      (Salicornioideae, Amaranthaceae).
AB  - BACKGROUND AND AIMS: Sarcocornia comprises about 28 species of perennial
      succulent halophytes distributed worldwide, mainly in saline environments of warm
      temperate and subtropical regions. The genus is characterized by strongly reduced
      leaves and flowers, which cause taxonomic difficulties; however, species in the
      genus show high diversity in growth form, with a mat-forming habit found in
      coastal salt marshes of all continents. Sarcocornia forms a monophyletic lineage
      with Salicornia whose species are all annual, yet the relationship between the
      two genera is poorly understood. This study is aimed at clarifying the
      phylogenetic relationship between Sarcocornia and Salicornia, interpreting
      biogeographical and ecological patterns in Sarcocornia, and gaining insights into
      putative parallel evolution of habit as an adaptation to environmental factors.
      METHODS: A comprehensively sampled and dated phylogeny of Sarcocornia is
      presented based on nuclear ribosomal DNA (external transcribed spacer) and
      chloroplast DNA (atpB-rbcL, rpl32-trnL) sequences; representative samples of
      Salicornia were also included in the analyses. To infer biogeographical patterns,
      an ancestral area reconstruction was conducted. KEY RESULTS: The
      Sarcocornia/Salicornia lineage arose during the Mid-Miocene from Eurasian
      ancestors and diversified into four subclades: the Salicornia clade, the American
      Sarcocornia clade, the Eurasian Sarcocornia clade and the South
      African/Australian Sarcocornia clade. Sarcocornia is supported as paraphyletic,
      with Salicornia nested within Sarcocornia being sister to the American/Eurasian
      Sarcocornia clade. The American and the South African/Australian Sarcocornia
      clade as well as the Salicornia clade were reconstructed to be of Eurasian
      origin. The prostrate, mat-forming habit arose multiple times in Sarcocornia.
      CONCLUSIONS: Sarcocornia diversified in salt-laden environments worldwide,
      repeatedly evolving superficially similar prostrate, mat-forming habits that seem
      advantageous in stressed environments with prolonged flooding, high tidal
      movement and frost. Some of these prostrate-habit types might be considered as
      ecotypes (e.g. S. pacifica or S. pillansii) while others represent good
      ecospecies (e.g. S. perennis, S. decumbens, S. capensis), hence representing
      different stages of speciation.

PMID- 25617411
TI  - Arabidopsis SHR and SCR transcription factors and AUX1 auxin influx carrier
      control the switch between adventitious rooting and xylogenesis in planta and in
      in vitro cultured thin cell layers.
AB  - BACKGROUND AND AIMS: Adventitious roots (ARs) are essential for vegetative
      propagation. The Arabidopsis thaliana transcription factors SHORT ROOT (SHR) and
      SCARECROW (SCR) affect primary/lateral root development, but their involvement in
      AR formation is uncertain. LAX3 and AUX1 auxin influx carriers contribute to
      primary/lateral root development. LAX3 expression is regulated by SHR, and LAX3
      contributes to AR tip auxin maximum. In contrast, AUX1 involvement in AR
      development is unknown. Xylogenesis is induced by auxin plus cytokinin as is AR
      formation, but the genes involved are largely unknown. Stem thin cell layers
      (TCLs) form ARs and undergo xylogenesis under the same auxin plus cytokinin
      input. The aim of this research was to investigate SHR, SCR, AUX1 and LAX3
      involvement in AR formation and xylogenesis in intact hypocotyls and stem TCLs in
      arabidopsis. METHODS: Hypocotyls of scr-1, shr-1, lax3, aux1-21 and lax3/aux1-21
      Arabidopsis thaliana null mutant seedlings grown with or without auxin plus
      cytokinin were examined histologically, as were stem TCLs cultured with auxin
      plus cytokinin. SCR and AUX1 expression was monitored using pSCR::GFP and
      AUX1::GUS lines, and LAX3 expression and auxin localization during xylogenesis
      were monitored by using LAX3::GUS and DR5::GUS lines. KEY RESULTS: AR formation
      was inhibited in all mutants, except lax3. SCR was expressed in pericycle
      anticlinally derived AR-forming cells of intact hypocotyls, and in cell clumps
      forming AR meristemoids of TCLs. The apex was anomalous in shr and scr ARs. In
      all mutant hypocotyls, the pericycle divided periclinally to produce xylogenesis.
      Xylary element maturation was favoured by auxin plus cytokinin in shr and aux1
      21. Xylogenesis was enhanced in TCLs, and in aux1-21 and shr in particular. AUX1
      was expressed before LAX3, i.e. in the early derivatives leading to either ARs or
      xylogenesis. CONCLUSIONS: AR formation and xylogenesis are developmental
      programmes that are inversely related, but they involve fine-tuning by the same
      proteins, namely SHR, SCR and AUX1. Pericycle activity is central for the
      equilibrium between xylary development and AR formation in the hypocotyl, with a
      role for AUX1 in switching between, and balancing of, the two developmental
      programmes.

PMID- 25617412
TI  - CypRules: a rule-based P450 inhibition prediction server.
AB  - Cytochrome P450 (CYPs) are the major enzymes involved in drug metabolism and
      bioactivation. Inhibition models were constructed for five of the most popular
      enzymes from the CYP superfamily in human liver. The five enzymes chosen for this
      study, namely CYP1A2, CYP2D6, CYP2C19, CYP2C9 and CYP3A4, account for 90% of the
      xenobiotic and drug metabolism in human body. CYP enzymes can be inhibited or
      induced by various drugs or chemical compounds. In this work, a rule-based CYP
      inhibition prediction online server, CypRules, was created based on predictive
      models generated by the rule-based C5.0 algorithm. CypRules can predict and
      provide structural rulesets for CYP inhibition for each compound uploaded to the
      server. Capable of fast execution performance, it can be used for virtual high
      throughput screening (VHTS) of a large set of testing compounds. AVAILABILITY AND
      IMPLEMENTATION: CypRules is freely accessible at http://cyprules.cmdm.tw/ and
      models, descriptor and program files for all compounds are publically available
      at http://cyprules.cmdm.tw/sources/sources.rar.

PMID- 25617413
TI  - 3USS: a web server for detecting alternative 3'UTRs from RNA-seq experiments.
AB  - Protein-coding genes with multiple alternative polyadenylation sites can generate
      mRNA 3'UTR sequences of different lengths, thereby causing the loss or gain of
      regulatory elements, which can affect stability, localization and translation
      efficiency. 3USS is a web-server developed with the aim of giving
      experimentalists the possibility to automatically identify alternative 3 ': UTRs
      (shorter or longer with respect to a reference transcriptome), an option that is
      not available in standard RNA-seq data analysis procedures. The tool reports as
      putative novel the 3 ': UTRs not annotated in available databases. Furthermore,
      if data from two related samples are uploaded, common and specific alternative 3
      ': UTRs are identified and reported by the server. AVAILABILITY AND
      IMPLEMENTATION: 3USS is freely available at
      http://www.biocomputing.it/3uss_server.

PMID- 25617414
TI  - Plant photosynthesis phenomics data quality control.
AB  - MOTIVATION: Plant phenomics, the collection of large-scale plant phenotype data,
      is growing exponentially. The resources have become essential component of modern
      plant science. Such complex datasets are critical for understanding the
      mechanisms governing energy intake and storage in plants, and this is essential
      for improving crop productivity. However, a major issue facing these efforts is
      the determination of the quality of phenotypic data. Automated methods are needed
      to identify and characterize alterations caused by system errors, all of which
      are difficult to remove in the data collection step and distinguish them from
      more interesting cases of altered biological responses. RESULTS: As a step
      towards solving this problem, we have developed a coarse-to-refined model called
      dynamic filter to identify abnormalities in plant photosynthesis phenotype data
      by comparing light responses of photosynthesis using a simplified kinetic model
      of photosynthesis. Dynamic filter employs an expectation-maximization process to
      adjust the kinetic model in coarse and refined regions to identify both
      abnormalities and biological outliers. The experimental results show that our
      algorithm can effectively identify most of the abnormalities in both real and
      synthetic datasets. AVAILABILITY AND IMPLEMENTATION: Software available at
      www.msu.edu/%7Ejinchen/DynamicFilter .

PMID- 25617415
TI  - ASSIGN: context-specific genomic profiling of multiple heterogeneous biological
      pathways.
AB  - MOTIVATION: Although gene-expression signature-based biomarkers are often
      developed for clinical diagnosis, many promising signatures fail to replicate
      during validation. One major challenge is that biological samples used to
      generate and validate the signature are often from heterogeneous biological
      contexts-controlled or in vitro samples may be used to generate the signature,
      but patient samples may be used for validation. In addition, systematic technical
      biases from multiple genome-profiling platforms often mask true biological
      variation. Addressing such challenges will enable us to better elucidate disease
      mechanisms and provide improved guidance for personalized therapeutics. RESULTS:
      Here, we present a pathway profiling toolkit, Adaptive Signature Selection and
      InteGratioN (ASSIGN), which enables robust and context-specific pathway analyses
      by efficiently capturing pathway activity in heterogeneous sets of samples and
      across profiling technologies. The ASSIGN framework is based on a flexible
      Bayesian factor analysis approach that allows for simultaneous profiling of
      multiple correlated pathways and for the adaptation of pathway signatures into
      specific disease. We demonstrate the robustness and versatility of ASSIGN in
      estimating pathway activity in simulated data, cell lines perturbed pathways and
      in primary tissues samples including The Cancer Genome Atlas breast carcinoma
      samples and liver samples exposed to genotoxic carcinogens. AVAILABILITY AND
      IMPLEMENTATION: Software for our approach is available for download at:
      http://www.bioconductor.org/packages/release/bioc/html/ASSIGN.html and
      https://github.com/wevanjohnson/ASSIGN.

PMID- 25617416
TI  - Quantitative visualization of alternative exon expression from RNA-seq data.
AB  - MOTIVATION: Analysis of RNA sequencing (RNA-Seq) data revealed that the vast
      majority of human genes express multiple mRNA isoforms, produced by alternative
      pre-mRNA splicing and other mechanisms, and that most alternative isoforms vary
      in expression between human tissues. As RNA-Seq datasets grow in size, it remains
      challenging to visualize isoform expression across multiple samples. RESULTS: To
      help address this problem, we present Sashimi plots, a quantitative visualization
      of aligned RNA-Seq reads that enables quantitative comparison of exon usage
      across samples or experimental conditions. Sashimi plots can be made using the
      Broad Integrated Genome Viewer or with a stand-alone command line program.
      AVAILABILITY AND IMPLEMENTATION: Software code and documentation freely available
      here: http://miso.readthedocs.org/en/fastmiso/sashimi.html

PMID- 25617417
TI  - A 68-year-old type 2 diabetic man of Korean ethnicity with fever, abdominal pain,
      and right eye visual disturbance.

PMID- 25617419
TI  - mRNA expression analysis of the SUMO pathway genes in the adult mouse retina.
AB  - Sumoylation is a reversible post-translational modification that regulates
      different cellular processes by conjugation/deconjugation of SUMO moieties to
      target proteins. Most work on the functional relevance of SUMO has focused on
      cell cycle, DNA repair and cancer in cultured cells, but data on the inter
      dependence of separate components of the SUMO pathway in highly specialized
      tissues, such as the retina, is still scanty. Nonetheless, several retinal
      transcription factors (TFs) relevant for cone and rod fate, as well as some
      circadian rhythm regulators, are regulated by sumoylation. Here we present a
      comprehensive survey of SUMO pathway gene expression in the murine retina by
      quantitative RT-PCR and in situ hybridization (ISH). The mRNA expression levels
      were quantified in retinas obtained under four different light/dark conditions,
      revealing distinct levels of gene expression. In addition, a SUMO pathway retinal
      gene atlas based on the mRNA expression pattern was drawn. Although most genes
      are ubiquitously expressed, some patterns could be defined in a first step to
      determine its biological significance and interdependence. The wide expression of
      the SUMO pathway genes, the transcriptional response under several light/dark
      conditions, and the diversity of expression patterns in different cell layers
      clearly support sumoylation as a relevant post-translational modification in the
      retina. This expression atlas intends to be a reference framework for retinal
      researchers and to depict a more comprehensive view of the SUMO-regulated
      processes in the retina. 

PMID- 25617420
TI  - mir-34b/c and mir-449a/b/c are required for spermatogenesis, but not for the
      first cleavage division in mice.
AB  - Mammalian sperm are carriers of not only the paternal genome, but also the
      paternal epigenome in the forms of DNA methylation, retained histones and
      noncoding RNAs. Although paternal DNA methylation and histone retention sites
      have been correlated with protein-coding genes that are critical for
      preimplantation embryonic development, physiological evidence of an essential
      role of these epigenetic marks in fertilization and early development remains
      lacking. Two miRNA clusters consisting of five miRNAs (miR-34b/c and miR
      449a/b/c) are present in sperm, but absent in oocytes, and miR-34c has been
      reported to be essential for the first cleavage division in vitro. Here, we show
      that both miR-34b/c- and miR-449-null male mice displayed normal fertility, and
      that intracytoplasmic injection of either miR-34b/c- or miR-449-null sperm led to
      normal fertilization, normal preimplantation development and normal birth rate.
      However, miR-34b/c and miR-449 double knockout (miR-dKO) males were infertile due
      to severe spermatogenic disruptions and oligo-astheno-teratozoospermia. Injection
      of miR-dKO sperm into wild-type oocytes led to a block at the two-pronucleus to
      zygote transition, whereas normal preimplantation development and healthy pups
      were obtained through injection of miR-dKO round spermatids. Our data demonstrate
      that miR-34b/c and miR-449a/b/c are essential for normal spermatogenesis and male
      fertility, but their presence in sperm is dispensable for fertilization and
      preimplantation development. 

PMID- 25617421
TI  - Macrophage migration inhibitory factor induces vascular leakage via autophagy.
AB  - Vascular leakage is an important feature of acute inflammatory shock, which
      currently has no effective treatment. Macrophage migration inhibitory factor
      (MIF) is a pro-inflammatory cytokine that can induce vascular leakage and plays
      an important role in the pathogenesis of shock. However, the mechanism of MIF
      induced vascular leakage is still unclear. In this study, using recombinant MIF
      (rMIF), we demonstrated that MIF induced disorganization and degradation of
      junction proteins and increased the permeability of human endothelial cells in
      vitro. Western blotting analysis showed that rMIF treatment induced LC3
      conversion and p62 degradation. Inhibition of autophagy with a PI3K inhibitor (3
      MA), a ROS scavenger (NAC) or autophagosomal-lysosomal fusion inhibitors
      (bafilomycin A1 and chloroquine) rescued rMIF-induced vascular leakage,
      suggesting that autophagy mediates MIF-induced vascular leakage. The potential
      involvement of other signaling pathways was also studied using different
      inhibitors, and the results suggested that MIF-induced vascular leakage may occur
      through the ERK pathway. In conclusion, we showed that MIF triggered autophagic
      degradation of endothelial cells, resulting in vascular leakage. Inhibition of
      MIF-induced autophagy may provide therapeutic targets against vascular leakage in
      inflammatory shock. 

PMID- 25617422
TI  - Netrins and Frazzled/DCC promote the migration and mesenchymal to epithelial
      transition of Drosophila midgut cells.
AB  - Mesenchymal-epithelial transitions (METs) are important in both development and
      the growth of secondary tumours. Although the molecular basis for epithelial
      polarity is well studied, less is known about the cues that induce MET. Here we
      show that Netrins, well known as chemotropic guidance factors, provide a basal
      polarising cue during the Drosophila midgut MET. Both netrinA and netrinB are
      expressed in the visceral mesoderm, the substrate upon which midgut cells
      migrate, while their receptor frazzled (fra) is expressed in midgut cells.
      Netrins are required to polarise Fra to the basal surface, and Netrins and Fra
      undergo mutually-dependent endocytosis, with Fra subsequently trafficking to late
      endosomes. Mutations to fra and netrins affect both migration and MET but to
      different degrees. Loss of fra strongly delays migration, midgut cells fail to
      extend protrusions, and apico-basal polarisation of proteins and epithelium
      formation is inhibited. In netrin mutants, the migration phenotype is weaker and
      cells still extend protrusions. However, apico-basal polarisation of proteins,
      including Fra, and FActin is greatly disrupted and a monolayer fails to form.
      Delocalised accumulations of FActin are prevalent in netrin mutants but not fra
      mutants suggesting delocalised Fra may disrupt the MET. betaPS localisation is
      also affected in netrin mutants in that a basal gradient is reduced while
      localisation to the midgut/VM interface is increased. Since a similar effect is
      seen when endocytosis is inhibited, Netrin and Fra may regulate Integrin
      turnover. The results suggest Netrin-dependent basal polarisation of Fra is
      critical for the formation of an epithelium. 

PMID- 25617423
TI  - Sixty minutes of what? A developing brain perspective for activating children
      with an integrative exercise approach.
AB  - Current recommendations for physical activity in children overlook the critical
      importance of motor skill acquisition early in life. Instead, they focus on the
      quantitative aspects of physical activity (eg, accumulate 60 min of daily
      moderate to vigorous physical activity) and selected health-related components of
      physical fitness (eg, aerobic fitness, muscular strength, muscular endurance,
      flexibility and body composition). This focus on exercise quantity in youth may
      limit considerations of qualitative aspects of programme design which include (1)
      skill development, (2) socialisation and (3) enjoyment of exercise. The timing of
      brain development and associated neuroplasticity for motor skill learning makes
      the preadolescence period a critical time to develop and reinforce fundamental
      movement skills in boys and girls. Children who do not participate regularly in
      structured motor skill-enriched activities during physical education classes or
      diverse youth sports programmes may never reach their genetic potential for motor
      skill control which underlies sustainable physical fitness later in life. The
      goals of this review are twofold: (1) challenge current dogma that is currently
      focused on the quantitative rather than qualitative aspects of physical activity
      recommendations for youth and (2) synthesise the latest evidence regarding the
      brain and motor control that will provide the foundation for integrative exercise
      programming that provide a framework sustainable activity for life. 

PMID- 25617424
TI  - BRAF Inhibition Stimulates Melanoma-Associated Macrophages to Drive Tumor Growth.
AB  - PURPOSE: To investigate the roles of melanoma-associated macrophages in melanoma
      resistance to BRAF inhibitors (BRAFi). EXPERIMENTAL DESIGN: An in vitro
      macrophage and melanoma cell coculture system was used to investigate whether
      macrophages play a role in melanoma resistance to BRAFi. The effects of
      macrophages in tumor resistance were examined by proliferation assay, cell death
      assay, and Western blot analyses. Furthermore, two mouse preclinical models were
      used to validate whether targeting macrophages can increase the antitumor
      activity of BRAFi. Finally, the number of macrophages in melanoma tissues was
      examined by immunohistochemistry. RESULTS: We demonstrate that in BRAF-mutant
      melanomas, BRAFi paradoxically activate the mitogen-activated protein kinase
      (MAPK) pathway in macrophages to produce VEGF, which reactivates the MAPK pathway
      and stimulates cell growth in melanoma cells. Blocking the MAPK pathway or VEGF
      signaling then reverses macrophage-mediated resistance. Targeting macrophages
      increases the antitumor activity of BRAFi in mouse and human tumor models. The
      presence of macrophages in melanomas predicts early relapse after therapy.
      CONCLUSIONS: Our findings demonstrate that macrophages play a critical role in
      melanoma resistance to BRAFi, suggesting that targeting macrophages will benefit
      patients with BRAF-mutant melanoma.

PMID- 25617425
TI  - MicroRNA in vitro diagnostics using immunoassay analyzers.
AB  - BACKGROUND: The implementation of new biomarkers into clinical practice is one of
      the most important areas in medical research. Besides their clinical impact,
      novel in vitro diagnostic markers promise to have a substantial effect on
      healthcare costs. Although numerous publications report the discovery of
      biomarkers, only a fraction of those markers are routinely used. One key
      challenge is a measurement system that is compatible with clinical workflows.
      METHODS: We designed a new immunoassay for microRNA (miRNA) quantification. The
      assay combines streptavidin-linked microparticles, a biotinylated catcher
      oligonucleotide complementary to a single miRNA species, and finally, a
      monoclonal antibody to DNA/RNA heterohybrids labeled with acridinium ester.
      Importantly, our assay runs on standard immunoassay analyzers. After a technical
      validation of the assay, we evaluated the clinical performance on 4 Alzheimer
      disease miRNAs. RESULTS: Our assay has an analytical specificity of 99.4% and is
      at the same time sensitive (concentrations in the range of 1 pmol/L miRNA can be
      reliably profiled). Because the novel approach did not require amplification
      steps, we obtained high reproducibility for up to 40 biological replicates.
      Importantly, our assay prototype exhibited a time to result of <3 h. With human
      blood samples, the assay was able to measure 4 miRNAs that can detect Alzheimer
      disease with a diagnostic accuracy of 82% and showed a Pearson correlation >0.994
      with the gold standard qRT-PCR. CONCLUSIONS: Our miRNA immunoassay allowed the
      measurement of miRNA signatures with sufficient analytical sensitivity and high
      specificity on commonly available laboratory equipment.

PMID- 25617426
TI  - Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of
      refractory adenovirus infection after HSCT.
AB  - Hematopoietic stem cell transplantation (HSCT) has improved over the last few
      decades. However, viral infections are often refractory to pharmacologic
      treatment and require alternative treatment strategies such as immunotherapy.
      Adenovirus (AdV) is th predominant disease-causing pathogen in pediatric HSCT. In
      a clinical trial, we analyzed safety and efficacy of ex vivo adoptive T-cell
      transfer (ACT) with hexon-specific T cells, predominantly of the T-helper cell 1
      (Th1) phenotype, in 30 patients with AdV disease or viremia. ACT was feasible
      with no acute toxicities or significant onset of graft-versus-host disease. ACT
      led to in vivo antiviral immunity for up to 6 months with viral control,
      resulting in complete clearance of viremia in 86% of patients with antigen
      specific T-cell responses. After ACT and a follow-up of 6 months, overall
      survival was markedly increased in responders (mean, 122 days; 15 survivors)
      compared with nonresponders who all died shortly after ACT (mean, 24 days; no
      survivors). AdV-related mortality was 100% in nonresponders compared with 9.5% in
      responders (>=1 log reduction of DNA copies per milliliter after ACT). In
      summary, ex vivo ACT of AdV-specific Th1 cells was well tolerated and led to
      successful and sustained restoration of T-cell immunity correlated with virologic
      response and protection from virus-related mortality. This cellular immunotherapy
      is a short-term available and broadly applicable treatment. The study is
      registered at European Union Clinical Trials Register as 2005-001092-35. 

PMID- 25617428
TI  - Long-range gene regulation and novel therapeutic applications.
AB  - An intimate relationship exists between nuclear architecture and gene activity.
      Unraveling the fine-scale three-dimensional structure of the genome and its
      impact on gene regulation is a major goal of current epigenetic research, one
      with direct implications for understanding the molecular mechanisms underlying
      human phenotypic variation and disease susceptibility. In this context, the novel
      revolutionary genome editing technologies and emerging new ways to manipulate
      genome folding offer new promises for the treatment of human disorders. 

PMID- 25617427
TI  - Factor VIII gene variants and inhibitor risk in African American hemophilia A
      patients.
AB  - African American hemophilia A (HA) patients experience a higher incidence of
      neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-a-vis white
      patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene
      encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African
      Americans. This study tested the hypothesis that immune responses to these sites
      provoke inhibitors. Blood samples were obtained from 174 African American and 198
      white HA subjects and their F8 gene sequences determined. Major
      histocompatibility complex class II binding and T-cell recognition of polymorphic
      sequences were evaluated using quantitative binding assays and HLA-DRB1
      tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to
      11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products
      having sequences at residues FVIII-484, 1241, and 2238 differing from those of
      putative proteins encoded by their F8 genes did not show high-avidity tetramer
      binding, whereas positive-control staining of tetanus-specific CD4 T cells was
      routinely successful. African Americans with an intron-22 inversion mutation
      showed a 2-3 times-higher inhibitor incidence than whites with the same mutation
      (odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the
      ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII
      products are unlikely to contribute appreciably to the inhibitor incidence in
      African Americans. 

PMID- 25617429
TI  - American Society of Nephrology quiz and questionnaire 2014: acid-base and
      electrolyte disorders.
AB  - The Nephrology Quiz and Questionnaire remains an extremely popular session for
      attendees of the Annual Kidney Week Meeting of the American Society of
      Nephrology. Once again, in 2014 the conference hall was overflowing with audience
      members and eager quiz participants. Topics covered by the expert discussants
      included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis,
      and transplantation. Complex cases from each of these categories along with
      single-best-answer questions were prepared and submitted by the panel of experts.
      Before the meeting, program directors of United States nephrology training
      programs and nephrology fellows answered the questions using an Internet-based
      questionnaire. During the live session, members of the audience tested their
      knowledge and judgment on a series of case-oriented questions prepared and
      discussed by the experts. They compared their answers in real time using audience
      response devices with the answers of the nephrology fellows and training program
      directors. The correct and incorrect answers were then discussed after the
      audience responses and the results of the questionnaire were displayed. As
      always, the audience, lecturers, and moderators enjoyed this educational session.
      This article recapitulates the acid-base and electrolyte disorders portion of the
      session and reproduces its educational value for the readers of the Clinical
      Journal of the American Society of Nephrology. Enjoy the clinical cases and
      expert discussions. 

PMID- 25617430
TI  - Accuracy of different equations in estimating GFR in pediatric kidney transplant
      recipients.
AB  - BACKGROUND AND OBJECTIVE: The knowledge of renal function is crucial for the
      management of pediatric kidney transplant recipients. In this population, the
      most commonly used plasma creatinine (PCr)-based or cystatin C (CystC)-based GFR
      predicting formulas may underperform (e.g., corticosteroids and trimethoprim may
      affect PCr concentration, whereas prednisone and calcineurin inhibitors may
      affect CystC concentration). This study evaluated the performance of six formulas
      in pediatric kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The study used PCr-based formulas (bedside Schwartz, Schwartz
      Lyon), CystC-based formulas (Hoek, Filler), and combined PCr-CystC-based formulas
      (CKD in Children [CKiD] 2012 and Zappitelli). The performance of these formulas
      was compared using inulin clearance as reference and assessed according to CKD
      stages in a historical cohort that included 73 pediatric kidney transplant
      recipients (199 measurements). The ability of the formulas to identify GFRs<60,
      <75, and <90 ml/min per 1.73 m(2) was assessed. RESULTS: At measured GFR (mGFR)
      >=90 ml/min per 1.73 m(2) (nine patients; 23 measurements), the Zappitelli
      formula had the highest 30% accuracy (P30) (95% [95% confidence interval (95%
      CI), 87% to 100%]) and the bedside Schwartz had the highest 10% accuracy (P10)
      (56% [95% CI, 32% to 72%]). At mGFR>=60 and <90 ml/min per 1.73 m(2) (22
      patients; 91 measurements), all formulas had P30 values >80%. However, only the
      CKiD 2012 formula had a P10 value >50%. At mGFR<60 ml/min per 1.73 m(2) (42
      patients; 85 measurements), the CKiD 2012 and Schwartz-Lyon formulas had the
      highest P10 (45% [95% CI, 34% to 55%] and 43% [95% CI, 33% to 54%]) and P30 (90%
      [95% CI, 84% to 97%] and 91% [95% CI, 86% to 98%]). All studied equations except
      Hoek and Filler had areas under the receiver-operating characteristic curves
      significantly >90% in discriminating patients with renal dysfunction at various
      CKD stages (GFR<60, <75, and <90 ml/min per 1.73 m(2)). CONCLUSIONS: In pediatric
      kidney transplant recipients, the CKiD 2012 formula had the best performance at
      mGFRs<90 ml/min per 1.73 m(2). CystC-based formulas were not superior to PCr
      based formulas.

PMID- 25617431
TI  - The cyclophilin A DIAGEOTROPICA gene affects auxin transport in both root and
      shoot to control lateral root formation.
AB  - Cyclophilin A is a conserved peptidyl-prolyl cis-trans isomerase (PPIase) best
      known as the cellular receptor of the immunosuppressant cyclosporine A. Despite
      significant effort, evidence of developmental functions of cyclophilin A in non
      plant systems has remained obscure. Mutations in a tomato (Solanum lycopersicum)
      cyclophilin A ortholog, DIAGEOTROPICA (DGT), have been shown to abolish the
      organogenesis of lateral roots; however, a mechanistic explanation of the
      phenotype is lacking. Here, we show that the dgt mutant lacks auxin maxima
      relevant to priming and specification of lateral root founder cells. DGT is
      expressed in shoot and root, and localizes to both the nucleus and cytoplasm
      during lateral root organogenesis. Mutation of ENTIRE/IAA9, a member of the auxin
      responsive Aux/IAA protein family of transcriptional repressors, partially
      restores the inability of dgt to initiate lateral root primordia but not the
      primordia outgrowth. By comparison, grafting of a wild-type scion restores the
      process of lateral root formation, consistent with participation of a mobile
      signal. Antibodies do not detect movement of the DGT protein into the dgt
      rootstock; however, experiments with radiolabeled auxin and an auxin-specific
      microelectrode demonstrate abnormal auxin fluxes. Functional studies of DGT in
      heterologous yeast and tobacco-leaf auxin-transport systems demonstrate that DGT
      negatively regulates PIN-FORMED (PIN) auxin efflux transporters by affecting
      their plasma membrane localization. Studies in tomato support complex effects of
      the dgt mutation on PIN expression level, expression domain and plasma membrane
      localization. Our data demonstrate that DGT regulates auxin transport in lateral
      root formation. 

PMID- 25617432
TI  - Vascular patterning regulates interdigital cell death by a ROS-mediated
      mechanism.
AB  - Blood vessels serve as key regulators of organogenesis by providing oxygen,
      nutrients and molecular signals. During limb development, programmed cell death
      (PCD) contributes to separation of the digits. Interestingly, prior to the onset
      of PCD, the autopod vasculature undergoes extensive patterning that results in
      high interdigital vascularity. Here, we show that in mice, the limb vasculature
      positively regulates interdigital PCD. In vivo, reduction in interdigital vessel
      number inhibited PCD, resulting in syndactyly, whereas an increment in vessel
      number and distribution resulted in elevation and expansion of PCD. Production of
      reactive oxygen species (ROS), toxic compounds that have been implicated in PCD,
      also depended on interdigital vascular patterning. Finally, ex vivo incubation of
      limbs in gradually decreasing oxygen levels led to a correlated reduction in both
      ROS production and interdigital PCD. The results support a role for oxygen in
      these processes and provide a mechanistic explanation for the counterintuitive
      positive role of the vasculature in PCD. In conclusion, we suggest a new role for
      vascular patterning during limb development in regulating interdigital PCD by ROS
      production. More broadly, we propose a double safety mechanism that restricts PCD
      to interdigital areas, as the genetic program of PCD provides the first layer and
      vascular patterning serves as the second. 

PMID- 25617433
TI  - Cavefish eye loss in response to an early block in retinal differentiation
      progression.
AB  - The troglomorphic phenotype shared by diverse cave-dwelling animals is regarded
      as a classical example of convergent evolution. One unresolved question is
      whether the characteristic eye loss in diverse cave species is based on
      interference with the same genetic program. Phreatichthys andruzzii, a Somalian
      cavefish, has evolved under constant conditions in complete darkness and shows
      severe troglomorphic characteristics, such as complete loss of eyes, pigments and
      scales. During early embryonic development, a complete eye is formed but is
      subsequently lost. In Astyanax mexicanus, another blind cavefish, eye loss has
      been attributed to interference during eye field patterning. To address whether
      similar pathways have been targeted by evolution independently, we investigated
      the retinal development of P. andruzzii, studying the expression of marker genes
      involved in eye patterning, morphogenesis, differentiation and maintenance. In
      contrast to Astyanax, patterning of the eye field and evagination of the optic
      vesicles proceeds without obvious deviation. However, the subsequent
      differentiation of retinal cell types is arrested during generation of the first
      born cell type, retinal ganglion cells, which also fail to project correctly to
      the optic tectum. Eye degeneration in both species is driven by progressive
      apoptosis. However, it is retinal apoptosis in Phreatichthys that progresses in a
      wave-like manner and eliminates progenitor cells that fail to differentiate, in
      contrast to Astyanax, where lens apoptosis appears to serve as a driving force.
      Thus, evolution has targeted late retinal differentiation events, indicating that
      there are several ways to discontinue the development and maintenance of an eye. 

PMID- 25617434
TI  - Plant embryogenesis requires AUX/LAX-mediated auxin influx.
AB  - The plant hormone auxin and its directional transport are known to play a crucial
      role in defining the embryonic axis and subsequent development of the body plan.
      Although the role of PIN auxin efflux transporters has been clearly assigned
      during embryonic shoot and root specification, the role of the auxin influx
      carriers AUX1 and LIKE-AUX1 (LAX) proteins is not well established. Here, we used
      chemical and genetic tools on Brassica napus microspore-derived embryos and
      Arabidopsis thaliana zygotic embryos, and demonstrate that AUX1, LAX1 and LAX2
      are required for both shoot and root pole formation, in concert with PIN efflux
      carriers. Furthermore, we uncovered a positive-feedback loop between MONOPTEROS
      (ARF5)-dependent auxin signalling and auxin transport. This MONOPTEROS-dependent
      transcriptional regulation of auxin influx (AUX1, LAX1 and LAX2) and auxin efflux
      (PIN1 and PIN4) carriers by MONOPTEROS helps to maintain proper auxin transport
      to the root tip. These results indicate that auxin-dependent cell specification
      during embryo development requires balanced auxin transport involving both influx
      and efflux mechanisms, and that this transport is maintained by a positive
      transcriptional feedback on auxin signalling. 

PMID- 25617435
TI  - UXT potentiates angiogenesis by attenuating Notch signaling.
AB  - Angiogenesis is spatially and temporally orchestrated by a myriad of signaling
      pathways, including the Notch signaling pathway. Here, we identified UXT as an
      evolutionarily conserved and developmentally expressed protein, indispensable for
      intersegmental vessel (ISV) formation in zebrafish. Deficiency of UXT in
      zebrafish embryos results in shorter ISVs, loss of tip cell behavior, and
      impairment of endothelial cell migration and division. Significantly, UXT
      attenuates the expression of the Notch-responsive genes in vitro and in vivo.
      Mechanistically, UXT binds to the promoters of the Notch signaling target genes
      and specifically interacts with the transactivation region domain of the Notch
      intracellular domain (NICD), impairing the interaction between NICD and the
      transcription factor RBP-Jkappa endogenously. This prevents RBP-Jkappa/CSL from
      activation and thus inhibits the consequent gene inductions. Furthermore,
      blockade of Notch signaling rescues the angiogenesis defect caused by UXT
      knockdown both in vitro and in vivo. Taken together, the data presented in this
      study characterize UXT as a novel repressor of Notch signaling, shedding new
      light on the molecular regulation of angiogenesis. 

PMID- 25617437
TI  - Communication between distant epithelial cells by filopodia-like protrusions
      during embryonic development.
AB  - Long-range intercellular communication is essential for the regulation of
      embryonic development. Apart from simple diffusion, various modes of signal
      transfer have been described in the literature. Here, we describe a novel type of
      cellular extensions found in epithelial cells of the somites in chicken embryos.
      These filopodia-like protrusions span the subectodermal space overlying the
      dorsal surface of the somites and contact the ectoderm. We show that these
      protrusions are actin- and tubulin-positive and require Rac1 for their formation.
      The presence of glycophosphatidylinositol-anchored proteins and net retrograde
      trafficking of the transmembrane Wnt-receptor Frizzled-7 along the protrusions
      indicate their role in signal transport and distribution. Taken together, our
      data suggest a role of filopodia-like protrusions in mediating signaling events
      between distant epithelial cells during embryonic development. 

PMID- 25617436
TI  - Snail2/Slug cooperates with Polycomb repressive complex 2 (PRC2) to regulate
      neural crest development.
AB  - Neural crest cells arise from the border of the neural plate and epidermal
      ectoderm, migrate extensively and differentiate into diverse cell types during
      vertebrate embryogenesis. Although much has been learnt about growth factor
      signals and gene regulatory networks that regulate neural crest development,
      limited information is available on how epigenetic mechanisms control this
      process. In this study, we show that Polycomb repressive complex 2 (PRC2)
      cooperates with the transcription factor Snail2/Slug to modulate neural crest
      development in Xenopus. The PRC2 core components Eed, Ezh2 and Suz12 are
      expressed in the neural crest cells and are required for neural crest marker
      expression. Knockdown of Ezh2, the catalytic subunit of PRC2 for histone H3K27
      methylation, results in defects in neural crest specification, migration and
      craniofacial cartilage formation. EZH2 interacts directly with Snail2, and Snail2
      fails to expand the neural crest domains in the absence of Ezh2. Chromatin
      immunoprecipitation analysis shows that Snail2 regulates EZH2 occupancy and
      histone H3K27 trimethylation levels at the promoter region of the Snail2 target E
      cadherin. Our results indicate that Snail2 cooperates with EZH2 and PRC2 to
      control expression of the genes important for neural crest specification and
      migration during neural crest development. 

PMID- 25617438
TI  - Jag1b is essential for patterning inner ear sensory cristae by regulating
      anterior morphogenetic tissue separation and preventing posterior cell death.
AB  - The sensory patches of the vertebrate inner ear, which contain hair cells and
      supporting cells, are essential for hearing and balance functions. How the
      stereotypically organized sensory patches are formed remains to be determined. In
      this study, we isolated a zebrafish mutant in which the jag1b gene is disrupted
      by an EGFP insertion. Loss of Jag1b causes cell death in the developing posterior
      crista and results in downregulation of fgf10a in the posterior prosensory cells.
      Inhibition of FGFR activity in wild-type embryos also causes loss of the
      posterior crista, suggesting that Fgf10a mediates Jag1b activity. By contrast, in
      the anterior prosensory domain, Jag1b regulates separation of a single
      morphogenetic field into anterior and lateral cristae by flattening cells
      destined to form a nonsensory epithelium between the two cristae. MAPK activation
      in the nonsensory epithelium precursors is required for the separation. In the
      jag1b mutant, MAPK activation and cell flattening are extended to anterior crista
      primordia, causing loss of anterior crista. More importantly, inhibition of MAPK
      activity, which blocks the differentiation of nonsensory epithelial cells,
      generated a fused large crista and extra hair cells. Thus, Jag1b uses two
      distinct mechanisms to form three sensory cristae in zebrafish. 

PMID- 25617439
TI  - Sepsis, confusion, rash, and pulmonary hemorrhage in a 36-year-old man with
      lymphoma.

PMID- 25617440
TI  - New rapid diagnostic tests: a real improvement for clinical use?

PMID- 25617441
TI  - Reply to "new rapid diagnostic tests: a real improvement for clinical use?".

PMID- 25617442
TI  - Microsporidian eye infection from outdoor recreational activities.

PMID- 25617443
TI  - Erratum for Jamieson et al., Whole-Genome Sequencing of the Mycobacterium
      tuberculosis Manila Sublineage Results in Less Clustering and Better Resolution
      than Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat
      (MIRU-VNTR) Typing and Spoligotyping.

PMID- 25617444
TI  - Correction for LaRocco et al., A Continuous Bovine Kidney Cell Line
      Constitutively Expressing Bovine alphaVbeta6 Integrin Has Increased
      Susceptibility to Foot-and-Mouth Disease Virus.

PMID- 25617445
TI  - Correction for dufresne et Al., instability of Aspergillus galactomannan in
      stored clinical samples.

PMID- 25617446
TI  - Retraction for Dinant et al., Aortic Homograft Endocarditis Caused by
      Campylobacter jejuni.

PMID- 25617449
TI  - Response to Letter to the Editor by Joe Brew, Department of Epidemiology,
      University of Florida.

PMID- 25617450
TI  - Reproduction potentiated in nematodes (Caenorhabditis elegans) and guppy fish
      (Poecilia reticulata) by adding a synthetic peptide to their aqueous environment.
AB  - Ambient exposure to a short synthetic peptide has enhanced fecundity (number of
      offspring) in invertebrates and vertebrates, ostensibly by disinhibiting
      reproduction. In separate experiments, nematodes (Caenorhabditis elegans) and
      guppy fish (Poecilia reticulata) were exposed via their aqueous environment to a
      dissolved synthetic hexamer (6mer) peptide, IEPVFT (EPL036), at a concentration
      of 1 MUmol l(-1). In the case of the worms, peptide was added to their aqueous
      buffer daily throughout the experiment (14 days); for the guppies, peptide
      administration was on the first 15 alternate days in a 50 week experiment.
      Fecundity rose by 79% among the worms. The number of descendants of the treated
      guppies was more than four times that of controls by week 26 (103 versus 25,
      including 72 juveniles versus 6), with 15.4% more estimated biomass in the test
      tank in total (i.e. including founders). It was deduced that treated females bred
      earlier, at a smaller size, and had larger brood sizes. The total number of fish
      in the control tank had caught up by termination, but biomass continued to lag
      the test tank. There were no overt signs of toxicity among either the worms or
      the fish. Bioinformatics has been unilluminating in explaining these results in
      terms, for example, of mimicry of an endogenous regulator. A mass spectrometric
      campaign to identify a receptor, using murine brain for expediency, proved
      inconclusive. Molecular modelling in silico indicated unexpectedly that the
      hexamer EPL036 might be acting as an antagonist, to pro-fecundity effect; that
      is, as a blocker of an inhibitor. This suggests that there awaits discovery an
      evolutionarily conserved reproductive inhibitor and its (anti-fecundity)
      receptor. 

PMID- 25617451
TI  - Biomechanics and energetics of running on uneven terrain.
AB  - In the natural world, legged animals regularly run across uneven terrain with
      remarkable ease. To gain understanding of how running on uneven terrain affects
      the biomechanics and energetics of locomotion, we studied human subjects (N=12)
      running at 2.3 m s(-1) on an uneven terrain treadmill, with up to a 2.5 cm height
      variation. We hypothesized that running on uneven terrain would show increased
      energy expenditure, step parameter variability and leg stiffness compared with
      running on smooth terrain. Subject energy expenditure increased by 5% (0.68 W kg(
      1); P<0.05) when running on uneven terrain compared with smooth terrain. Step
      width and length variability also increased by 27% and 26%, respectively
      (P<0.05). Positive and negative ankle work decreased on uneven terrain by 22%
      (0.413 J kg(-1)) and 18% (0.147 J kg(-1)), respectively (P=0.0001 and P=0.0008).
      Mean muscle activity increased on uneven terrain for three muscles in the thigh
      (P<0.05). Leg stiffness also increased by 20% (P<0.05) during running on uneven
      terrain compared with smooth terrain. Calculations of gravitational potential
      energy fluctuations suggest that about half of the energetic increases can be
      explained by additional positive and negative mechanical work for up and down
      steps on the uneven surface. This is consistent between walking and running, as
      the absolute increases in energetic cost for walking and running on uneven
      terrain were similar: 0.68 and 0.48 W kg(-1), respectively. These results provide
      insight into how surface smoothness can affect locomotion biomechanics and
      energetics in the real world. 

PMID- 25617452
TI  - Common measures of immune function vary with time of day and sampling protocol in
      five passerine species.
AB  - Ecological immunology is a rapidly growing field of study that focuses on
      understanding variation in immune systems across species and how this relates to
      species ecology and evolution. Newly developed field methods aimed at studying
      variation in immune function in a field setting have yielded many insights.
      Nonetheless, there continues to be much debate regarding the interpretation of
      field measures of immune function. There is substantial evidence to suggest that
      handling stress could introduce variation into measures of immune function, yet
      no study has examined the impacts of incremental changes in handling times under
      30 min on immune measures. Nor has any study examined variation in immune
      function with time of day, though other physiological measures, including
      glucocorticoids known to impact immune function, vary with time of day. Here, I
      used observational field data to test the hypothesis that innate immune function
      varies with handling stress. Furthermore, I tested the hypothesis that innate
      immune function changes over the course of the day. I show that measures of
      innate immune function vary with (1) handling stress over short time periods
      typical of sample collection in the field, and (2) the time of day that an
      individual is sampled. I discuss these findings from an ecological perspective
      and suggest that the observed variation is not random, but is likely to have
      important adaptive functions. I end with a summary of the practical implications
      of these findings for field studies of ecological immunology. 

PMID- 25617453
TI  - Nutrient balancing of the adult worker bumblebee (Bombus terrestris) depends on
      the dietary source of essential amino acids.
AB  - Animals carefully regulate the amount of protein that they consume. The quantity
      of individual essential amino acids (EAAs) obtained from dietary protein depends
      on the protein source, but how the proportion of EAAs in the diet affects
      nutrient balancing has rarely been studied. Recent research using the Geometric
      Framework for Nutrition has revealed that forager honeybees who receive much of
      their dietary EAAs from floral nectar and not from solid protein have relatively
      low requirements for dietary EAAs. Here, we examined the nutritional requirements
      for protein and carbohydrates of foragers of the buff-tailed bumblebee Bombus
      terrestris. By using protein (sodium caseinate) or an equimolar mixture of the 10
      EAAs, we found that the intake target (nutritional optimum) of adult workers
      depended on the source and proportion of dietary EAAs. When bees consumed
      caseinate-containing diets in a range of ratios between 1:250 and 1:25 (protein
      to carbohydrate), they achieved an intake target (IT) of 1:149 (w/w). In contrast
      to those fed protein, bees fed the EAA diets had an IT more biased towards
      carbohydrates (1:560 w/w) but also had a greater risk of death than those fed
      caseinate. We also tested how the dietary source of EAAs affected free AAs in bee
      haemolymph. Bees fed diets near their IT had similar haemolymph AA profiles,
      whereas bees fed diets high in caseinate had elevated levels of leucine,
      threonine, valine and alanine in the haemolymph. We found that like honeybees,
      bumblebee workers prioritize carbohydrate intake and have a relatively low
      requirement for protein. The dietary source of EAAs influenced both the ratio of
      protein/EAA to carbohydrate and the overall amount of carbohydrate eaten. Our
      data support the idea that EAAs and carbohydrates in haemolymph are important
      determinants of nutritional state in insects. 

PMID- 25617454
TI  - Symbiont type influences trophic plasticity of a model cnidarian-dinoflagellate
      symbiosis.
AB  - The association between cnidarians and photosynthetic dinoflagellates within the
      genus Symbiodinium is a prevalent relationship in tropical and subtropical marine
      environments. Although the diversity of Symbiodinium provides a possible axis for
      niche diversification, increased functional range and resilience to physical
      stressors such as elevated temperature, how such diversity relates to the
      physiological balance between autotrophy and heterotrophy of the host animal
      remains unknown. Here, we experimentally show interspecific and intraspecific
      variability of photosynthetic carbon fixation and subsequent translocation by
      Symbiodinium to the model cnidarian host Aiptasia pallida. By using a clonal
      anemone line harboring different species of Symbiodinium, we determined that
      symbiont identity influences trophic plasticity through its density, capacity to
      fix carbon, quantity of translocated carbon and ultimately the host's capacity to
      ingest and digest prey. Symbiont carbon translocation and host prey ingestion
      were positively correlated across symbiont combinations that consisted of
      different isoclonal lines of Symbiodinium minutum, while a combination with type
      D4-5 Symbiodinium displayed lower carbon translocation, and prey capture and
      digestion more similar to Aiptasia lacking symbionts. The absence of a shift
      toward greater heterotrophy when carbon translocation is low suggests that the
      metabolic demand of feeding and digestion may overwhelm nutritional stores when
      photosynthesis is reduced, and amends the possible role of animal feeding in
      resistance to or recovery from the effects of climate change in more obligate
      symbioses such as reef-building corals. 

PMID- 25617455
TI  - How effective are acoustic signals in territorial defence in the Lusitanian
      toadfish?
AB  - The function of fish sounds in territorial defence, in particular its influence
      on the intruder's behaviour during territorial invasions, is poorly known.
      Breeding Lusitanian toadfish males (Halobatrachus didactylus) use sounds
      (boatwhistles) to defend nests from intruders. Results from a previous study
      suggest that boatwhistles function as a 'keep-out signal' during territorial
      defence. To test this hypothesis we performed territorial intrusion experiments
      with muted Lusitanian toadfish. Males were muted by making a cut and deflating
      the swimbladder (the sound-producing apparatus) under anaesthesia. Toadfish nest
      holder males reacted to intruders mainly by emitting sounds (sham-operated and
      control groups) and less frequently with escalated bouts of fighting. When the
      nest-holder produced a boatwhistle, the intruder fled more frequently than
      expected by chance alone. Muted males experienced a higher number of intrusions
      than the other groups, probably because of their inability to vocalise. Together,
      our results show that fish acoustic signals are effective deterrents in
      nest/territorial intrusions, similar to bird song. 

PMID- 25617456
TI  - Streamwise vortices destabilize swimming bluegill sunfish (Lepomis macrochirus).
AB  - In their natural environment, fish must swim stably through unsteady flows and
      vortices, including vertical vortices, typically shed by posts in a flow,
      horizontal cross-flow vortices, often produced by a step or a waterfall in a
      stream, and streamwise vortices, where the axis of rotation is aligned with the
      direction of the flow. Streamwise vortices are commonly shed by bluff bodies in
      streams and by ships' propellers and axial turbines, but we know little about
      their effects on fish. Here, we describe how bluegill sunfish use more energy and
      are destabilized more often in flow with strong streamwise vorticity. The
      vortices were created inside a sealed flow tank by an array of four turbines with
      similar diameter to the experimental fish. We measured oxygen consumption for
      seven sunfish swimming at 1.5 body lengths (BL) s(-1) with the turbines rotating
      at 2 Hz and with the turbines off (control). Simultaneously, we filmed the fish
      ventrally and recorded the fraction of time spent maneuvering side-to-side and
      accelerating forward. Separately, we also recorded lateral and ventral video for
      a combination of swimming speeds (0.5, 1.5 and 2.5 BL s(-1)) and turbine speeds
      (0, 1, 2 and 3 Hz), immediately after turning the turbines on and 10 min later to
      test for accommodation. Bluegill sunfish are negatively affected by streamwise
      vorticity. Spills (loss of heading), maneuvers and accelerations were more
      frequent when the turbines were on than in the control treatment. These unsteady
      behaviors, particularly acceleration, correlated with an increase in oxygen
      consumption in the vortex flow. Bluegill sunfish are generally fast to recover
      from roll perturbations and do so by moving their pectoral fins. The frequency of
      spills decreased after the turbines had run for 10 min, but was still markedly
      higher than in the control, showing that fish partially adapt to streamwise
      vorticity, but not completely. Coping with streamwise vorticity may be an
      important energetic cost for stream fishes or migratory fishes. 

PMID- 25617457
TI  - Feeding in billfishes: inferring the role of the rostrum from a biomechanical
      standpoint.
AB  - Perhaps the most striking feature of billfishes is the extreme elongation of the
      premaxillary bones forming their rostra. Surprisingly, the exact role of this
      structure in feeding is still controversial. The goal of this study is to
      investigate the use of the rostrum from a functional, biomechanical and
      morphological standpoint to ultimately infer its possible role during feeding.
      Using beam theory, experimental and theoretical loading tests were performed on
      the rostra from two morphologically different billfish, the blue marlin (Makaira
      nigricans) and the swordfish (Xiphias gladius). Two loading regimes were applied
      (dorsoventral and lateral) to simulate possible striking behaviors. Histological
      samples and material properties of the rostra were obtained along their lengths
      to further characterize structure and mechanical performance. Intraspecific
      results show similar stress distributions for most regions of the rostra,
      suggesting that this structure may be designed to withstand continuous loadings
      with no particular region of stress concentration. Although material stiffness
      increased distally, flexural stiffness increased proximally owing to higher
      second moment of area. The blue marlin rostrum was stiffer and resisted
      considerably higher loads for both loading planes compared with that of the
      swordfish. However, when a continuous load along the rostrum was considered,
      simulating the rostrum swinging through the water, swordfish exhibited lower
      stress and drag during lateral loading. Our combined results suggest that the
      swordfish rostrum is suited for lateral swiping to incapacitate their prey,
      whereas the blue marlin rostrum is better suited to strike prey from a wider
      variety of directions. 

PMID- 25617458
TI  - Regulatory mechanisms of metabolic flexibility in the dark-eyed junco (Junco
      hyemalis).
AB  - Small temperate birds reversibly modify their aerobic performance to maintain
      thermoregulatory homeostasis under seasonally changing environmental conditions
      and these physiological adjustments may be attributable to changes in the
      expression of genes in the underlying regulatory networks. Here, we report the
      results of an experimental procedure designed to gain insight into the
      fundamental mechanisms of metabolic flexibility in the dark-eyed junco (Junco
      hyemalis). We combined genomic transcriptional profiles with measures of
      metabolic enzyme activities and whole-animal thermogenic performance from juncos
      exposed to four 6-week acclimation treatments that varied in temperature (cold, 3
      degrees C; warm, 24 degrees C) and photoperiod (short day, 8 h light:16 h dark;
      long day, 16 h light:8 h dark). Cold-acclimated birds increased thermogenic
      capacity compared with warm-acclimated birds, and this enhanced performance was
      associated with upregulation of genes involved in muscle hypertrophy,
      angiogenesis, and lipid transport and oxidation, as well as with catabolic enzyme
      activities. These physiological changes occurred over ecologically relevant
      timescales, suggesting that birds make regulatory adjustments to interacting,
      hierarchical pathways in order to seasonally enhance thermogenic capacity. 

PMID- 25617459
TI  - Spectral sensitivity in Onychophora (velvet worms) revealed by
      electroretinograms, phototactic behaviour and opsin gene expression.
AB  - Onychophorans typically possess a pair of simple eyes, inherited from the last
      common ancestor of Panarthropoda (Onychophora+Tardigrada+Arthropoda). These
      visual organs are thought to be homologous to the arthropod median ocelli,
      whereas the compound eyes probably evolved in the arthropod lineage. To gain
      insights into the ancestral function and evolution of the visual system in
      panarthropods, we investigated phototactic behaviour, opsin gene expression and
      the spectral sensitivity of the eyes in two representative species of
      Onychophora: Euperipatoides rowelli (Peripatopsidae) and Principapillatus
      hitoyensis (Peripatidae). Our behavioural analyses, in conjunction with previous
      data, demonstrate that both species exhibit photonegative responses to
      wavelengths ranging from ultraviolet to green light (370-530 nm), and
      electroretinograms reveal that the onychophoran eye is maximally sensitive to
      blue light (peak sensitivity ~480 nm). Template fits to these sensitivities
      suggest that the onychophoran eye is monochromatic. To clarify which type of
      opsin the single visual pigment is based on, we localised the corresponding mRNA
      in the onychophoran eye and brain using in situ hybridization. Our data show that
      the r-opsin gene (onychopsin) is expressed exclusively in the photoreceptor cells
      of the eye, whereas c-opsin mRNA is confined to the optic ganglion cells and the
      brain. Together, our findings suggest that the onychopsin is involved in vision,
      whereas c-opsin might have a photoreceptive, non-visual function in
      onychophorans. 

PMID- 25617460
TI  - Response to a change in the target nest during ant relocation.
AB  - Decisions regarding spatial and temporal choices pertaining to a wide range of
      activities such as mating, feeding and resting are necessary for all organisms.
      Social species encounter another level of complexity, wherein inputs from
      multiple individuals have to be consolidated to yield a consensus. One platform
      on which decision making can be examined is the relocation of animal societies.
      Relocation is the process by which organisms move from their old dwelling to a
      new nest along with all the inhabitants. This exposes them to the elements and
      thus impacts their survival and reproduction. Diacamma indicum, the model system
      for our experiments is a ponerine ant that uses tandem running for colony
      relocation. In the present study an artificial manipulation was performed to
      cause a shift in the target nest. The flexibility of the relocation process and,
      more specifically, the response of tandem leaders to a changed target were
      studied. A majority of these leaders (N=262) not only re-evaluated and adapted to
      the change, but did so with negligible error (1.65%). This enabled colonies
      (N=10) to reunite at the target nest in every case. The only cost to this
      flexible decision making was paid in terms of additional time. Although
      considered to be a primitive method of recruitment, we reveal that tandem running
      allows D. indicum leaders to incorporate assessment of the available options at
      every step. This inherent flexibility in decision making would be a good strategy
      for organisms that need to function with incomplete information or inhabit
      environments that change frequently. 

PMID- 25617461
TI  - Vocalisations of the bigeye Pempheris adspersa: characteristics, source level and
      active space.
AB  - Fish sounds are an important biological component of the underwater soundscape.
      Understanding species-specific sounds and their associated behaviour is critical
      for determining how animals use the biological component of the soundscape. Using
      both field and laboratory experiments, we describe the sound production of a
      nocturnal planktivore, Pempheris adspersa (New Zealand bigeye), and provide
      calculations for the potential effective distance of the sound for intraspecific
      communication. Bigeye vocalisations recorded in the field were confirmed as such
      by tank recordings. They can be described as popping sounds, with individual pops
      of short duration (7.9+/-0.3 ms) and a peak frequency of 405+/-12 Hz. Sound
      production varied during a 24 h period, with peak vocalisation activity occurring
      during the night, when the fish are most active. The source level of the bigeye
      vocalisation was 115.8+/-0.2 dB re. 1 uPa at 1 m, which is relatively quiet
      compared with other soniferous fish. Effective calling range, or active space,
      depended on both season and lunar phase, with a maximum calling distance of 31.6
      m and a minimum of 0.6 m. The bigeyes' nocturnal behaviour, characteristics of
      their vocalisation, source level and the spatial scale of its active space
      reported in the current study demonstrate the potential for fish vocalisations to
      function effectively as contact calls for maintaining school cohesion in
      darkness. 

PMID- 25617462
TI  - Making Olympic lizards: the effects of specialised exercise training on
      performance.
AB  - Exercise training is well known to affect a suite of physiological and
      performance traits in mammals, but effects of training in other vertebrate
      tetrapod groups have been inconsistent. We examined performance and physiological
      differences among green anole lizards (Anolis carolinensis) that were trained for
      sprinting or endurance, using an increasingly rigorous training regimen over 8
      weeks. Lizards trained for endurance had significantly higher post-training
      endurance capacity compared with the other treatment groups, but groups did not
      show post-training differences in sprint speed. Although acclimation to the
      laboratory environment and training explain some of our results, mechanistic
      explanations for these results correspond with the observed performance
      differences. After training, endurance-trained lizards had higher haematocrit and
      larger fast glycolytic muscle fibres. Despite no detectable change in maximal
      performance of sprint-trained lizards, we detected that they had significantly
      larger slow oxidative muscle fibre areas compared with the other treatments.
      Treatment groups did not differ in the proportion of number of fibre types, nor
      in the mass of most limb muscles or the heart. Our results offer some caveats for
      investigators conducting training research on non-model organisms and they reveal
      that muscle plasticity in response to training may be widespread
      phylogenetically. 

PMID- 25617463
TI  - Sequential exposure to a combination of stressors blocks memory reconsolidation
      in Lymnaea.
AB  - Stress alters the formation of long-term memory (LTM) in Lymnaea. When snails are
      exposed to more than one stressor, however, how the memory is altered becomes
      complicated. Here, we investigated how multiple stressors applied in a specific
      pattern affect an aspect of memory not often studied in regards to stress -
      reconsolidation. We hypothesized that the application of a sequence of stressors
      would block the reconsolidation process. Reconsolidation occurs following
      activation of a previously formed memory. Sequential crowding and handling were
      used as the stressors to block reconsolidation. When the two stressors were
      sequentially presented immediately following memory activation, reconsolidation
      was blocked. However, if the sequential presentation of the stressors was delayed
      for 1 h after memory activation, reconsolidation was not blocked. That is, LTM
      was observed. Finally, presentation of either stressor alone did not block
      reconsolidation. Thus, stressors can block reconsolidation, which may be
      preferable to pharmacological manipulations. 

PMID- 25617464
TI  - The role of egg-nest contrast in the rejection of brood parasitic eggs.
AB  - Hosts of avian brood parasites can avoid the reproductive costs of raising
      genetically unrelated offspring by rejecting parasitic eggs. The perceptual cues
      and controls mediating parasitic egg discrimination and ejection are well
      studied: hosts are thought to use differences in egg color, brightness,
      maculation, size and shape to discriminate between their own and foreign eggs.
      Most theories of brood parasitism implicitly assume that the primary criteria to
      which hosts attend when discriminating eggs are differences between the eggs
      themselves. However, this assumption is confounded by the degree to which
      chromatic and achromatic characteristics of the nest lining co-vary with egg
      coloration, so that egg-nest contrast per se might be the recognition cue driving
      parasitic egg detection. Here, we systematically tested whether and how egg-nest
      contrast itself contributes to foreign egg discrimination. In an artificial
      parasitism experiment, we independently manipulated egg color and nest lining
      color of the egg-ejector American robin (Turdus migratorius), a host of the
      obligate brood parasitic brown-headed cowbird (Molothrus ater). We hypothesized
      that the degree of contrast between foreign eggs and the nest background would
      affect host egg rejection behavior. We predicted that experimentally decreasing
      egg-nest chromatic and achromatic contrast (i.e. rendering parasitic eggs more
      cryptic against the nest lining) would decrease rejection rates, while increasing
      egg-nest contrast would increase rejection rates. In contrast to our predictions,
      egg-nest contrast was not a significant predictor of egg ejection patterns.
      Instead, egg color significantly predicted responses to parasitism. We conclude
      that egg-egg differences are the primary drivers of egg rejection in this system.
      Future studies should test for the effects of egg-nest contrast per se in
      predicting parasitic egg recognition in other host-parasite systems, including
      those hosts building enclosed nests and those parasites laying cryptic eggs, as
      an alternative to hypothesized effects of egg-egg contrast. 

PMID- 25617465
TI  - Variation in early-life telomere dynamics in a long-lived bird: links to
      environmental conditions and survival.
AB  - Conditions experienced during early life can have profound consequences for both
      short- and long-term fitness. Variation in the natal environment has been shown
      to influence survival and reproductive performance of entire cohorts in wild
      vertebrate populations. Telomere dynamics potentially provide a link between the
      early environment and long-term fitness outcomes, yet we know little about how
      the environment can influence telomere dynamics in early life. We found that
      environmental conditions during growth have an important influence on early-life
      telomere length (TL) and attrition in nestlings of a long-lived bird, the
      European storm petrel Hydrobates pelagicus. Nestlings reared under unfavourable
      environmental conditions experienced significantly greater telomere loss during
      postnatal development compared with nestlings reared under more favourable natal
      conditions, which displayed a negligible change in TL. There was, however, no
      significant difference in pre-fledging TL between cohorts. The results suggest
      that early-life telomere dynamics could contribute to the marked differences in
      life-history traits that can arise among cohorts reared under different
      environmental conditions. Early-life TL was also found to be a significant
      predictor of survival during the nestling phase, providing further evidence for a
      link between variation in TL and individual fitness. To what extent the
      relationship between early-life TL and mortality during the nestling phase is a
      consequence of genetic, parental and environmental factors is currently unknown,
      but it is an interesting area for future research. Accelerated telomere attrition
      under unfavourable conditions, as observed in this study, might play a role in
      mediating the effects of the early-life environment on later-life performance. 

PMID- 25617466
TI  - The effects of acute salinity challenges on osmoregulation in Mozambique tilapia
      reared in a tidally changing salinity.
AB  - This study characterizes the differences in osmoregulatory capacity among
      Mozambique tilapia, Oreochromis mossambicus, reared in freshwater (FW), in
      seawater (SW) or under tidally driven changes in salinity. This was addressed
      through the use of an abrupt exposure to a change in salinity. We measured
      changes in: (1) plasma osmolality and prolactin (PRL) levels; (2) pituitary
      expression of prolactin (PRL) and its receptors, PRLR1 and PRLR2; (3) branchial
      expression of PRLR1, PRLR2, Na(+)/Cl(-) co-transporter (NCC), Na(+)/K(+)/2Cl(-)
      co-transporter (NKCC), alpha1a and alpha1b isoforms of Na(+)/K(+)-ATPase (NKA),
      cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3)
      and Na(+)/H(+) exchanger 3 (NHE3). Mozambique tilapia reared in a tidal
      environment successfully adapted to SW while fish reared in FW did not survive a
      transfer to SW beyond the 6 h sampling. With the exception of CFTR, the change in
      the expression of ion pumps, transporters and channels was more gradual in fish
      transferred from tidally changing salinities to SW than in fish transferred from
      FW to SW. Upon transfer to SW, the increase in CFTR expression was more robust in
      tidal fish than in FW fish. Tidal and SW fish successfully adapted when
      transferred to FW. These results suggest that Mozambique tilapia reared in a
      tidally changing salinity, a condition that more closely represents their natural
      history, gain an adaptive advantage compared with fish reared in FW when facing a
      hyperosmotic challenge. 

PMID- 25617467
TI  - Evolutionary adaptations for the temporal processing of natural sounds by the
      anuran peripheral auditory system.
AB  - Sensory systems function most efficiently when processing natural stimuli, such
      as vocalizations, and it is thought that this reflects evolutionary adaptation.
      Among the best-described examples of evolutionary adaptation in the auditory
      system are the frequent matches between spectral tuning in both the peripheral
      and central auditory systems of anurans (frogs and toads) and the frequency
      spectra of conspecific calls. Tuning to the temporal properties of conspecific
      calls is less well established, and in anurans has so far been documented only in
      the central auditory system. Using auditory-evoked potentials, we asked whether
      there are species-specific or sex-specific adaptations of the auditory systems of
      gray treefrogs (Hyla chrysoscelis) and green treefrogs (H. cinerea) to the
      temporal modulations present in conspecific calls. Modulation rate transfer
      functions (MRTFs) constructed from auditory steady-state responses revealed that
      each species was more sensitive than the other to the modulation rates typical of
      conspecific advertisement calls. In addition, auditory brainstem responses (ABRs)
      to paired clicks indicated relatively better temporal resolution in green
      treefrogs, which could represent an adaptation to the faster modulation rates
      present in the calls of this species. MRTFs and recovery of ABRs to paired clicks
      were generally similar between the sexes, and we found no evidence that males
      were more sensitive than females to the temporal modulation patterns
      characteristic of the aggressive calls used in male-male competition. Together,
      our results suggest that efficient processing of the temporal properties of
      behaviorally relevant sounds begins at potentially very early stages of the
      anuran auditory system that include the periphery. 

PMID- 25617468
TI  - Methylation of microRNA genes regulates gene expression in bisexual flower
      development in andromonoecious poplar.
AB  - Previous studies showed sex-specific DNA methylation and expression of candidate
      genes in bisexual flowers of andromonoecious poplar, but the regulatory
      relationship between methylation and microRNAs (miRNAs) remains unclear. To
      investigate whether the methylation of miRNA genes regulates gene expression in
      bisexual flower development, the methylome, microRNA, and transcriptome were
      examined in female and male flowers of andromonoecious poplar. 27 636 methylated
      coding genes and 113 methylated miRNA genes were identified. In the coding genes,
      64.5% of the methylated reads mapped to the gene body region; by contrast, 60.7%
      of methylated reads in miRNA genes mainly mapped in the 5' and 3' flanking
      regions. CHH methylation showed the highest methylation levels and CHG showed the
      lowest methylation levels. Correlation analysis showed a significant, negative,
      strand-specific correlation of methylation and miRNA gene expression (r=0.79, P
      <0.05). The methylated miRNA genes included eight long miRNAs (lmiRNAs) of 24
      nucleotides and 11 miRNAs related to flower development. miRNA172b might play an
      important role in the regulation of bisexual flower development-related gene
      expression in andromonoecious poplar, via modification of methylation.
      Gynomonoecious, female, and male poplars were used to validate the methylation
      patterns of the miRNA172b gene, implying that hyper-methylation in
      andromonoecious and gynomonoecious poplar might function as an important
      regulator in bisexual flower development. Our data provide a useful resource for
      the study of flower development in poplar and improve our understanding of the
      effect of epigenetic regulation on genes other than protein-coding genes. 

PMID- 25617469
TI  - The divining root: moisture-driven responses of roots at the micro- and macro
      scale.
AB  - Water is fundamental to plant life, but the mechanisms by which plant roots sense
      and respond to variations in water availability in the soil are poorly
      understood. Many studies of responses to water deficit have focused on large
      scale effects of this stress, but have overlooked responses at the sub-organ or
      cellular level that give rise to emergent whole-plant phenotypes. We have
      recently discovered hydropatterning, an adaptive environmental response in which
      roots position new lateral branches according to the spatial distribution of
      available water across the circumferential axis. This discovery illustrates that
      roots are capable of sensing and responding to water availability at spatial
      scales far lower than those normally studied for such processes. This review will
      explore how roots respond to water availability with an emphasis on what is
      currently known at different spatial scales. Beginning at the micro-scale, there
      is a discussion of water physiology at the cellular level and proposed sensory
      mechanisms cells use to detect osmotic status. The implications of these
      principles are then explored in the context of cell and organ growth under non
      stress and water-deficit conditions. Following this, several adaptive responses
      employed by roots to tailor their functionality to the local moisture environment
      are discussed, including patterning of lateral root development and generation of
      hydraulic barriers to limit water loss. We speculate that these micro-scale
      responses are necessary for optimal functionality of the root system in a
      heterogeneous moisture environment, allowing for efficient water uptake with
      minimal water loss during periods of drought. 

PMID- 25617470
TI  - Metabolic and transcriptional transitions in barley glumes reveal a role as
      transitory resource buffers during endosperm filling.
AB  - During grain filling in barley (Hordeum vulgare L. cv. Barke) reserves are
      remobilized from vegetative organs. Glumes represent the vegetative tissues
      closest to grains, senesce late, and are involved in the conversion of
      assimilates. To analyse glume development and metabolism related to grain
      filling, parallel transcript and metabolite profiling in glumes and endosperm
      were performed, showing that glume metabolism and development adjusts to changing
      grain demands, reflected by specific signatures of metabolite and transcript
      abundances. Before high endosperm sink strength is established by storage product
      accumulation, glumes form early, intermediary sink organs, shifting then to
      remobilizing and exporting source organs. Metabolic and transcriptional
      transitions occur at two phases: first, at the onset of endosperm filling, as a
      consequence of endosperm sink activity and assimilate depletion in endosperm and
      vascular tissues; second, at late grain filling, by developmental ageing and
      senescence. Regulation of and transition between phases are probably governed by
      specific NAC and WRKY transcription factors, and both abscisic and jasmonic acid,
      and are accompanied by changed expression of specific nitrogen transporters.
      Expression and metabolite profiling suggest glume-specific mechanisms of
      assimilate conversion and translocation. In summary, grain filling and endosperm
      sink strength coordinate phase changes in glumes via metabolic, hormonal, and
      transcriptional control. This study provides a comprehensive view of barley glume
      development and metabolism, and identifies candidate genes and associated
      pathways, potentially important for breeding improved grain traits. 

PMID- 25617471
TI  - IL-15 amplifies the pathogenic properties of CD4+CD28- T cells in multiple
      sclerosis.
AB  - CD4(+)CD28(-) T cells arise through repeated antigenic stimulation and are
      present in diseased tissues of patients with various autoimmune disorders,
      including multiple sclerosis (MS). These cells are believed to have cytotoxic
      properties that contribute to the pathogenic damaging of the target organ.
      Endogenous cues that are increased in the diseased tissue may amplify the
      activity of CD4(+)CD28(-) T cells. In this study, we focused on IL-15, a
      cytotoxicity-promoting cytokine that is increased in the serum and cerebrospinal
      fluid of MS patients. Using immunohistochemistry, we demonstrate that IL-15 is
      mainly produced by astrocytes and infiltrating macrophages in inflammatory
      lesions of MS patients. Moreover, in vitro transmigration studies reveal that IL
      15 selectively attracts CD4(+)CD28(-) T cells of MS patients, but not of healthy
      individuals. IL-15 further induces the expression of chemokine receptors and
      adhesion molecules on CD4(+)CD28(-) T cells, as investigated using flow
      cytometry, resulting in enhanced migration over a monolayer of human brain
      endothelial cells. Finally, flow cytometric analyses revealed that IL-15
      increases the proliferation and production of GM-CSF, expression of cytotoxic
      molecules (NKG2D, perforin, and granzyme B), and degranulation capacity of
      CD4(+)CD28(-) T cells. Taken together, these findings indicate that increased
      peripheral and local levels of IL-15 amplify the pathogenic potential of
      CD4(+)CD28(-) T cells, thus contributing to tissue damage in MS brain lesions. 

PMID- 25617472
TI  - Regulation of asymmetric division and CD8+ T lymphocyte fate specification by
      protein kinase Czeta and protein kinase Clambda/iota.
AB  - During an immune response against a microbial pathogen, activated naive T
      lymphocytes give rise to effector cells that provide acute host defense and
      memory cells that provide long-lived immunity. It has been shown that T
      lymphocytes can undergo asymmetric division, enabling the daughter cells to
      inherit unequal amounts of fate-determining proteins and thereby acquire distinct
      fates from their inception. In this study, we show that the absence of the
      atypical protein kinase C (PKC) isoforms, PKCzeta and PKClambda/iota, disrupts
      asymmetric CD8(+) T lymphocyte division. These alterations were associated with
      aberrant acquisition of a pre-effector transcriptional program, detected by
      single-cell gene expression analyses, in lymphocytes that had undergone their
      first division in vivo and enhanced differentiation toward effector fates at the
      expense of memory fates. Together, these results demonstrate a role for atypical
      PKC in regulating asymmetric division and the specification of divergent CD8(+) T
      lymphocyte fates early during an immune response. 

PMID- 25617473
TI  - IL-33 is required for disposal of unnecessary cells during ovarian atresia
      through regulation of autophagy and macrophage migration.
AB  - Physiological processes such as ovarian follicle atresia generate large amounts
      of unnecessary cells or tissue detritus, which needs to be disposed of rapidly.
      IL-33 is a member of the IL-1 cytokine gene family. Constitutive expression of IL
      33 in a wide range of tissues has hinted at its role beyond immune defense. We
      have previously reported a close correlation between IL-33 expression patterns
      and ovarian atresia. In this study, we demonstrated that IL-33 is required for
      disposal of degenerative tissue during ovarian atresia using Il33(-/-) mice.
      Deletion of the Il33 gene impaired normal disposal of atretic follicles,
      resulting in massive accumulations of tissue wastes abundant with aging-related
      catabolic wastes such as lipofuscin. Accumulation of tissue wastes in Il33(-/-)
      mice, in turn, accelerated ovarian aging and functional decline. Thus, their
      reproductive life span was shortened to two thirds of that for Il33(+/-)
      littermates. IL-33 orchestrated disposal mechanism through regulation of
      autophagy in degenerating tissues and macrophage migration into the tissues. Our
      study provides direct evidence supporting an expanded role of IL-33 in tissue
      integrity and aging through regulating disposal of unnecessary tissues or cells. 

PMID- 25617476
TI  - Bio-based resistance inducers for sustainable plant protection against pathogens.
AB  - An increasing demand for environmentally acceptable alternative for traditional
      pesticides provides an impetus to conceive new bio-based strategies in crop
      protection. Employing induced resistance is one such strategy, consisting of
      boosting the natural plant immunity. Upon infections, plants defend themselves by
      activating their immune mechanisms. These are initiated after the recognition of
      an invading pathogen via the microbe-associated molecular patterns (MAMPs) or
      other microbe-derived molecules. Triggered responses inhibit pathogen spread from
      the infected site. Systemic signal transport even enables to prepare, i.e. prime,
      distal uninfected tissues for more rapid and enhanced response upon the
      consequent pathogen attack. Similar defense mechanisms can be triggered by
      purified MAMPs, pathogen-derived molecules, signal molecules involved in plant
      resistance to pathogens, such as salicylic and jasmonic acid, or a wide range of
      other chemical compounds. Induced resistance can be also conferred by plant
      associated microorganisms, including beneficial bacteria or fungi. Treatment with
      resistance inducers or beneficial microorganisms provides long-lasting resistance
      for plants to a wide range of pathogens. This study surveys current knowledge on
      resistance and its mechanisms provided by microbe-, algae- and plant-derived
      elicitors in different crops. The main scope deals with bacterial substances and
      fungus-derived molecules chitin and chitosan and algae elicitors, including
      naturally sulphated polysaccharides such as ulvans, fucans or carageenans. Recent
      advances in the utilization of this strategy in practical crop protection are
      also discussed. 

PMID- 25617474
TI  - HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument
      protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells
      from seropositive asymptomatic individuals and protect humanized HLA-A*02:01
      transgenic mice against ocular herpes.
AB  - The HSV type 1 tegument virion phosphoprotein (VP) 11/12 (VP11/12) is a major Ag
      targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether
      and which VP11/12 epitope-specific CD8(+) T cells play a role in the "natural"
      protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who
      have never had clinical herpes disease) remain to be determined. In this study,
      we used multiple prediction computer-assisted algorithms to identify 10 potential
      HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of
      VP11/12. Three of 10 epitopes exhibited high-to-moderate binding affinity to HLA
      A*02:01 molecules. In 10 sequentially studied HLA-A*02:01-positive and HSV-1
      seropositive ASYMP individuals, the most frequent, robust, and polyfunctional
      effector CD8(+) T cell responses, as assessed by a combination of tetramer
      frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation,
      IFN-gamma, and multiplex cytokines assays, were predominantly directed against
      three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710. Interestingly,
      ASYMP individuals had a significantly higher proportion of
      CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory
      CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic
      individuals (with a history of numerous episodes of recurrent ocular herpetic
      disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three
      ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific
      CD8(+) TEM cells that were associated with a strong protective immunity against
      ocular herpes infection and disease. Our findings outline phenotypic and
      functional features of protective HSV-specific CD8(+) T cells that should guide
      the development of an effective T cell-based herpes vaccine. 

PMID- 25617475
TI  - An essential role for RGS protein/Galphai2 interactions in B lymphocyte-directed
      cell migration and trafficking.
AB  - Chemokines engage B lymphocyte surface receptors, triggering heterotrimeric G
      protein Galphai subunit guanine nucleotide exchange. RGS proteins limit the
      duration that Galphai subunits remain GTP bound, and the loss of an individual
      RGS protein typically enhances chemokine receptor signaling. In this study, we
      show that B cells carrying a Galphai2 (G184S/G184S) mutation that disables all
      RGS protein/Galphai2 interactions exhibit an unexpectedly severe reduction in
      chemokine receptor signaling. The Galphai2 (G184S/G184S) B cells have markedly
      elevated basal calcium levels, but poor chemokine-induced increases, enhanced
      nonspecific migration, but extremely poor chemotaxis. In striking contrast, the
      Galphai2 (G184S/G184S) B cells exhibited enhanced sensitivity to sphingosine 1
      phosphate (S1P). S1P elicited heightened intracellular calcium responses and
      enhanced S1P-triggered cell migration. Mice with the Galphai2 (G184S/G184S)
      mutation displayed excessive numbers of germinal center-like structures; abnormal
      serum Ig profiles; and aberrant B lymphocyte trafficking. These findings
      establish an essential role for RGS proteins in B cell chemoattractant signaling
      and for the proper position of B lymphocytes in lymphoid organs. 

PMID- 25617477
TI  - Hippocampal theta rhythm after local administration of procaine or amphetamine
      into the ventral tegmental area in fear conditioned rats.
AB  - The ventral tegmental area (VTA) is thought to be an important component in the
      mesocorticolimbic system involved in the regulation of theta rhythm in the
      hippocampus. In this study we investigate the effect of pharmacological
      inactivation (local procaine infusion) or activation (local amphetamine infusion)
      of the VTA on theta rhythm parameters during task specific behavior in fear
      conditioned, freely moving rats. Animals were implanted with bilateral recording
      electrodes into the dorsal hippocampus (CA1) and bilateral injection cannulas
      into the VTA. Behavioral activities and hippocampal local field potentials (LFP)
      were recorded throughout the experiment, in pre- and post-injection conditions.
      We found that intra-VTA injection of procaine temporarily suppressed fear
      conditioned avoidance response (escape from the foot-shock arena) and also
      influenced hippocampal theta rhythm parameters during immobility linked with
      arousal and/or attention. Procaine infusion decreased the signal power (Pmax) of
      theta rhythm during immobility behavior, in comparison to the control group
      (water infusion), whereas administration of amphetamine had no effect on the
      behavior and hippocampal LFP. Our results indicate that temporal inactivation of
      neuronal activity in the VTA affects hippocampal theta rhythm linked with
      attentional immobility and suppresses avoidance response in fear conditioned
      animals. 

PMID- 25617479
TI  - Modulatory effects of l-arginine and soy enriched diet on bone homeostasis
      abnormalities in streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is a complex syndrome which is responsible for numerous
      complications affecting the whole body. Osteoporosis is regarded as one of the
      chronic complications of diabetes mellitus that results from reduced bone
      formation and increased resorption. In this context, we searched for dietary
      supplements that preserve diabetic bone loss. Parathyroid hormone (PTH) has been
      suggested as a possible mechanism affecting bone homeostasis in streptozotocin
      (STZ)-induced diabetic rats. The osteoprotective effects of l-arginine and soy
      enriched diet were also investigated. Male Wistar rats were allocated into four
      groups; normal control, untreated STZ-diabetic rats and STZ-diabetic rats treated
      with either l-arginine (10mg/kg/day) or fed soy enriched diet (200 g/kg diet) for
      12 weeks. l-Arginine and soy enriched diet normalized serum PTH level and
      increased serum osteocalcin level; bone osteocalcin, osteoprotegerin and runt
      related transcription factor2 mRNA levels compared to diabetic rats. A decrease
      in serum pyridinoline, C-terminal telopeptides of type I collagen, cathepsin k
      levels and bone cathepsin k mRNA level was observed in both treated groups. Both
      treatments increased serum insulin and insulin like growth factor-1 levels and
      decreased urinary calcium excretion. In conclusion, l-arginine and soy enriched
      diet are effective in prevention of osteoporosis associated with diabetes
      mellitus.

PMID- 25617480
TI  - Camel milk attenuates the biochemical and morphological features of diabetic
      nephropathy: inhibition of Smad1 and collagen type IV synthesis.
AB  - Diabetic nephropathy (DN) is a common microvascular complication of diabetes
      mellitus (DM) that worsens its morbidity and mortality. There is evidence that
      camel milk (CM) improves the glycemic control in DM but its effect on the renal
      complications especially the DN remains unclear. Thus the current study aimed to
      characterize the effects of CM treatment on streptozotocin (STZ)-induced DN.
      Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney
      function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose,
      insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase
      (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was
      also examined. The current results showed that rats with untreated diabetes
      exhibited marked hyperglycemia, IR, high serum urea and creatinine levels,
      excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and
      extracellular matrix deposition. There was also increased lipid peroxidation
      products, decreased antioxidant enzyme activity and GSH levels. Camel milk
      treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide
      dismutase and CAT expression, CAT activity, and GSH levels were increased. The
      renoprotective effects of CM were demonstrated by the decreased serum urea and
      creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular
      morphology. In conclusion, beside its hypoglycemic action, CM attenuates the
      early changes of DN, decreased renal Smad1 and Col4. This could be attributed to
      a primary action on the glomerular mesangial cells, or secondarily to the
      hypoglycemic and antioxidant effects of CM. The protective effects of CM against
      DN support its use as an adjuvant anti-diabetes therapy. 

PMID- 25617481
TI  - Protective effects of the flavonoid hesperidin methyl chalcone in inflammation
      and pain in mice: role of TRPV1, oxidative stress, cytokines and NF-kappaB.
AB  - Cytokines and reactive oxygen species are inflammatory mediators that lead to
      increased sensitivity to painful stimuli, and their inhibition represents a
      therapeutic approach in controlling acute and chronic pain. The water-soluble
      flavonone hesperidin methyl chalcone (HMC) is used in the treatment of venous
      diseases, but its bioactivity as anti-inflammatory and analgesic is poorly
      understood. The present study evaluated the protective effects of HMC in widely
      used mouse models of acute and prolonged inflammation and pain. Male Swiss mice
      were treated with HMC (3-100 or 30 mg/kg, intraperitoneally) or vehicle (saline)
      1h before inflammatory stimuli. In overt pain-like behavior tests, HMC inhibited
      acetic acid- and phenyl-p-benzoquinone-induced writhing, and capsaicin-, Complete
      Freund's Adjuvant (CFA)- and formalin-induced paw flinching and licking. HMC also
      inhibited carrageenan-, capsaicin- and CFA-induced mechanical and thermal
      hyperalgesia. Mechanistically, HMC inhibited carrageenan-induced cytokine (TNF
      alpha, IL-1beta, IL-6, and IL-10) production, oxidative stress and NF-kappaB
      activation. Furthermore, HMC did not cause gastric or hepatic injury in a 7 days
      treatment protocol. Thus, this is the first report that HMC reduces inflammation
      and inflammatory pain by targeting TRPV1 (transient receptor potential vanilloid
      type 1) receptor activity, oxidative stress, cytokine production, and NF-kappaB
      activity, which suggests its potential applicability in inflammatory diseases.

PMID- 25617478
TI  - Mechanisms of distal axonal degeneration in peripheral neuropathies.
AB  - Peripheral neuropathy is a common complication of a variety of diseases and
      treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV,
      hepatitis C, and Campylobacter jejuni). Despite the fundamental difference
      between these insults, peripheral neuropathy develops as a combination of just
      six primary mechanisms: altered metabolism, covalent modification, altered
      organelle function and reactive oxygen species formation, altered intracellular
      and inflammatory signaling, slowed axonal transport, and altered ion channel
      dynamics and expression. All of these pathways converge to lead to axon
      dysfunction and symptoms of neuropathy. The detailed mechanisms of axon
      degeneration itself have begun to be elucidated with studies of animal models
      with altered degeneration kinetics, including the slowed Wallerian degeneration
      (Wld(S)) and Sarm knockout animal models. These studies have shown axonal
      degeneration to occur through a programmed pathway of injury signaling and
      cytoskeletal degradation. Insights into the common disease insults that converge
      on the axonal degeneration pathway promise to facilitate the development of
      therapeutics that may be effective against other mechanisms of neurodegeneration.

PMID- 25617482
TI  - Amino acid residues that affect the basicity of the catalytic glutamate of the
      hydrolytic aldehyde dehydrogenases.
AB  - In the catalytic mechanism of hydrolytic aldehyde dehydrogenases (ALDHs) the role
      of Glu268 (mature human ALDH2 numbering) as a general base is of major relevance.
      Since Glu268 basicity depends on its protein environment, here we explore its
      interactions with other amino acid residues in the three different conformations
      observed in ALDH crystal-structures: "inside", "intermediate" and "outside". In
      all of them Glu268 is in a hydrophobic environment. In the "inside" conformation,
      the theoretical pKa estimated by PROPKA3 is the result of the effects of hydrogen
      bonds with the protonated thiol of the catalytic Cys302 and/or the main-chain
      amide nitrogen of the highly conserved Gly270, and of charge-charge interactions
      with neighboring side-chains-Lys178, Glu/Asp476, His465 or Glu399 depending on
      the enzyme. In the "intermediate" conformation Glu268-carboxyl pKa is influenced
      by interactions with Glu/Asp476, Arg/Lys475, Lys/Arg178, His465 or Arg459, also
      depending on the enzyme. In the "outside" conformation, the effects on Glu268
      carboxyl pKa arise from hydrogen bonds with the side chains of the strictly
      conserved Thr224 and/or of Lys/Arg178, and from charge-charge interactions with
      Lys/Arg/Asp178, Glu476, or Arg459. The estimated pKas and interactions of Glu268
      carboxyl in the "intermediate" and "outside" conformations are consistent with
      their previously proposed roles in activating the hydrolytic water and in a
      proton relay mechanism, respectively. Water channels connecting Glu268 with the
      bulk water were found in all hydrolytic ALDHs. In the "inside" conformation the
      theoretical pKas of the Glu268-carboxyl and Cys302-thiol groups suggest that the
      carboxyl cannot receive the proton from the thiol. We propose that a protonated
      Cys302 might perform the nucleophilic attack on the aldehyde, which can be
      facilitated by Glu268 in the "intermediate" conformation. Finally, the
      conservation of the residues influencing Glu268 basicity between and within ALDH
      families suggests that these residues, not previously studied, are important for
      the catalytic mechanism of many ALDH enzymes. 

PMID- 25617483
TI  - The cytotoxic effects of brown Cuban propolis depend on the nemorosone content
      and may be mediated by mitochondrial uncoupling.
AB  - Three main types of Cuban propolis directly related to their secondary metabolite
      composition have been identified: brown, red and yellow propolis; the former is
      majoritarian and is characterized by the presence of nemorosone. In this study,
      brown Cuban propolis extracts were found cytotoxic against HepG2 cells and
      primary rat hepatocytes, in close association with the nemorosone contents. In
      mitochondria isolated from rat liver the extracts displayed uncoupling activity,
      which was demonstrated by the increase in succinate-supported state 4 respiration
      rates, dissipation of mitochondrial membrane potential, Ca(2+) release from
      Ca(2+)-loaded mitochondria, and a marked ATP depletion. As in cells, the degree
      of such mitotoxic events was closely correlated to the nemorosone content. The
      propolis extracts that do not contain nemorosone were neither cytotoxic nor
      mitotoxic, except R-29, whose detrimental effect upon cells and mitochondria
      could be mediated by its isoflavonoids and chalcones components, well known
      mitochondrial uncouplers. Our results at least partly unravel the cytotoxic
      mechanism of Cuban propolis, particularly regarding brown propolis, and raise
      concerns about the toxicological implication of Cuban propolis consumption. 

PMID- 25617484
TI  - Recovery of redox homeostasis altered by CuNPs in H4IIE liver cells does not
      reduce the cytotoxic effects of these NPs: an investigation using aryl
      hydrocarbon receptor (AhR) dependent antioxidant activity.
AB  - The generation of reactive oxygen species (ROS) and consequent oxidative stress
      is regarded as a relevant mechanism for nanoparticle toxicity. In cells, the
      activation of the aryl hydrocarbon receptor (AhR) triggers a cascade of defence
      responses against oxidative stress. By increasing AhR dependent cellular anti
      oxidant activity, we tested the extent to which the cytotoxic effect of copper
      nanoparticles (CuNPs) is governed by oxidative stress. H4IIE rat hepatoma cells
      were challenged with high ROS levels after exposure to CuNPs, while the AhR
      induced cellular anti-oxidant defence was simultaneously activated by the AhR
      ligand beta-Naphthoflavone (betaNF). Activation of phase II detoxification
      enzymes (as glutathione-S-transferases, GSTs) and anti-oxidants (glutathione,
      GSH) led to a complete abrogation of CuNP-induced ROS production. However, a
      concurrent reduction in cytotoxicity was not detected, thereby indicating that
      CuNPs exert non-oxidative stress mediated cytotoxic effects. Transmission
      electron microscopy analysis pointed to a direct physical perturbation of
      cellular structures by CuNPs, thus contributing to their cytotoxicity. Our
      observations highlight that distinct mechanisms underlie the toxicity of ions and
      NPs and indicate that while ROS elicitation is CuNP-specific, the cytotoxic
      action of these particles may not be directly related to their pro-oxidative
      activity. These findings have important implications with respect to the
      oxidative stress paradigm used to explain NP toxicity. 

PMID- 25617485
TI  - HSD17B1 expression enhances estrogen signaling stimulated by the low active
      estrone, evidenced by an estrogen responsive element-driven reporter gene in
      vivo.
AB  - Hydroxysteroid (17beta) dehydrogenase 1 (HSD17B1) belongs to a family of short
      chain-dehydrogenases. The enzyme utilizes NAD(P) and NAD(P)H as cofactors, and
      catalyzes the reversible reaction between estrone (E1) and estradiol (E2) in
      vitro. Of these steroids, E1 presents with lower estrogenic activity, but is
      converted to highly active E2 by HSD17B1. HSD17B1 is expressed especially in
      tissues with a high E2-producing capacity such as human ovaries and placenta, but
      also in several peripheral estrogen target tissues in humans, and inhibiting the
      enzyme activity is, thus, considered a promising approach to treat estrogen
      dependent diseases. By analyzing transgenic mice universally expressing human
      HSD17B1 and carrying estrogen-response element (ERE)-driven luciferase reporter
      gene (Bi-transgenic ERELuc-HSD17B1TG mice) we showed a markedly higher reporter
      gene activity in various peripheral tissues of these mice as compared with ERELuc
      mice, indicating enhanced estrogen response generated by human HSD17B1
      expression. An increased response after E1 administration was also evident in the
      Bi-TG mice, indicated by the increased uterus growth response and by the higher
      ERELuc reporter gene activity in the uterus. Moreover, a HSD17B1 inhibitor
      significantly reduced E1-induced increase in the uterus weight and uterine
      epithelial proliferation in the Bi-TG mice. Also the E1-induced ERELuc activity
      in the inhibitor-treated uterus was reduced by the HSD17B1 inhibitor in immature
      mice ex vivo, as well as in the liver of adult mice. The data, thus, demonstrate
      the potential use of the Bi-TG mice as a preclinical in vivo model for screening
      the efficacy of HSD17B1 inhibitors. As compared with the existing models, the Bi
      TG mice present with luciferase activity as an additional, easily quantitative
      endpoint for the estrogen action. 

PMID- 25617486
TI  - Organisation of in-hospital cardiac arrest teams - a nationwide study.
AB  - BACKGROUND: In-hospital cardiac arrests are treated by a team of health care
      providers. Improving team performance may increase survival. Currently, no
      international standards for cardiac arrest teams exist in terms of member
      composition and allocation of tasks. AIM: To describe the composition of in
      hospital cardiac arrest teams and review pre-arrest allocation of tasks. METHODS:
      A nationwide cross-sectional study was performed. Data on cardiac arrest teams
      and pre-arrest allocation of tasks were collected from protocols on resuscitation
      required for hospital accreditation in Denmark. Additional data were collected
      through telephone interviews and email correspondence. Psychiatric hospitals and
      hospitals serving outpatients only were excluded. RESULTS: Data on the cardiac
      arrest team were available from 44 of 47 hospitals. The median team size was 5
      (25th percentile; 75th percentile: 4; 6) members. Teams included a nurse
      anaesthetist (100%), a medical house officer (82%), an orderly (73%), an
      anaesthesiology house officer (64%) and a medical assistant (20%). Less likely to
      participate was a cardiology house officer (23%) or a cardiology specialist
      registrar (5%). Overall, a specialist registrar was represented on 20% of teams
      and 20% of cardiac arrest teams had a different team composition during nights
      and weekends. In total, 41% of teams did not define a team leader pre-arrest, and
      the majority of the teams did not define the tasks of the remaining team members.
      CONCLUSION: In Denmark, there are major differences among cardiac arrest teams.
      This includes team size, profession of team members, medical specialty and
      seniority of the physicians. Nearly half of the hospitals do not define a cardiac
      arrest team leader and the majority do not define the tasks of the remaining team
      members.

PMID- 25617487
TI  - Analysis of out-of-hospital cardiac arrest location and public access
      defibrillator placement in Metropolitan Phoenix, Arizona.
AB  - OBJECTIVES: Automated external defibrillators (AEDs) improve outcomes from out-of
      hospital cardiac arrest (OHCA) but are infrequently used. We sought to compare
      the locations of OHCAs and AEDs in metropolitan Phoenix, Arizona. METHODS: Public
      location OHCAs and AEDs were geocoded utilizing a statewide OHCA database (1/2010
      12/2012) and AED registry. OHCAs were mapped using kernel-density estimation and
      overlapped with AED placements. Spearman's rho was obtained to determine the
      correlation between OHCA incidents and AED locations. RESULTS: A total of 654
      consecutive public location OHCAs and all 1704 non-medical facility AEDs
      registered in the study area were included in the analysis. High OHCA incident
      areas lacking AEDs were identified in the kernel-density surface map. OHCA
      event/AED correlation analysis showed a weak correlation (Spearman's rho=0.283;
      p=0.002). Events occurred most frequently at locations categorized as "In
      Cars/Roads/Parking lots" (190/654, 29.1%) and there were no identified AEDs for
      these areas. AEDs were placed most frequently in "Public
      business/Office/Workplace" and cardiac arrests occurred with the second highest
      frequency in this location type. CONCLUSION: There was a weak correlation between
      OHCA events and deployed AEDs. It was possible to identify areas where OHCAs
      occurred frequently but AEDs were lacking. The ability to correlate the sites of
      OHCAs and AED locations is a necessary step toward improving the effectiveness of
      public access defibrillation.

PMID- 25617488
TI  - Response to the letter to the editor by Negrini et al.

PMID- 25617489
TI  - Comments to Bodega et al. (2015).

PMID- 25617490
TI  - Molecular phylogenetics and phylogeographic structure of Sorex bedfordiae based
      on mitochondrial and nuclear DNA sequences.
AB  - The southeastern margin of the Tibetan Plateau is characterized by complex
      topography and a discontinuous landscape, creating a sky island situation.
      However, the way topography shapes genetic structures and demographic histories
      of endemic species has not been well studied. We examined the phylogeographic
      pattern and demographic histories of Sorex bedfordiae, a dispersal-limited small
      mammal, using three nuclear genes [1977bp] and two mitochondrial genes [1794bp]
      with comprehensive molecular approaches. We recovered five well-supported clades
      whose distributions are along mountain ridges and roughly subdivided by large
      rivers. Demographic expansions in the middle Pleistocene were strongly supported
      by both nuclear and mitochondrial genes. Our results support the hypothesis that
      sky island topography and river systems strongly affect the genetic structure of
      non-aquatic terrestrial species. We further clarify that S. bedfordiae and S.
      cylindricauda are valid sibling species, whereas S. excelsus is most likely a
      geographic subspecies of S. bedfordiae. 

PMID- 25617491
TI  - Meprin alpha and meprin beta: Procollagen proteinases in health and disease.
AB  - Metalloproteases meprin alpha and meprin beta were recently discovered as
      procollagen proteinases, capable of cleaving off the globular C- and N-terminal
      prodomains of fibrillar collagen type I and type III. This proteolytic process is
      indeed sufficient to induce collagen fibril assembly as visualized by
      transmission electron microscopy. The biological relevance was demonstrated with
      the help of meprin alpha and meprin beta knock-out mice, which exhibit decreased
      collagen deposition in skin resulting in impaired tensile strength. On the other
      hand, overexpression of meprin metalloproteases was found under fibrotic
      conditions in the skin (keloids) and the lung (pulmonary hypertension). Thus,
      regulation of meprin activity by specific inhibition to reduce collagen
      maturation might be a suitable approach for the treatment of certain pathological
      conditions. 

PMID- 25617492
TI  - Matrix metalloproteinases in fish biology and matrix turnover.
AB  - Matrix metalloproteinases have important functions for tissue turnover in fish,
      with relevance both for the fish industry and molecular and cellular research on
      embryology, inflammation and tissue repair. These metalloproteinases have been
      studied in different fish types, subjected to both aquaculture and experimental
      conditions. This review highlights studies on these metalloproteinases in
      relation to both fish quality and health and further, the future importance of
      fish for basic research studies. 

PMID- 25617493
TI  - Matrix metalloproteinases in stem cell mobilization.
AB  - Hematopoietic stem cells (HSCs) have the capability to migrate back and forth
      between their preferred microenvironment in bone marrow niches and the peripheral
      blood, but under steady-state conditions only a marginal number of stem cells can
      be found in the circulation. Different mobilizing agents, however, which create a
      highly proteolytic milieu in the bone marrow, can drastically increase the number
      of circulating HSCs. Among other proteases secreted and membrane-bound matrix
      metalloproteinases (MMPs) are known to be involved in the induced mobilization
      process and can digest niche-specific extracellular matrix components and
      cytokines responsible for stem cell retention to the niches. Iatrogenic stem cell
      mobilization and stem cell homing to their niches are clinically employed on a
      routine basis, although the exact mechanisms of both processes are still not
      fully understood. In this review we provide an overview on the various roles of
      MMPs in the induced release of HSCs from the bone marrow. 

PMID- 25617494
TI  - Reassessing immune control of hepatitis A virus.
AB  - There is renewed interest in hepatitis A virus (HAV) pathogenesis and immunity
      after 2-3 decades of limited progress. From a public health perspective, the
      average age at infection has increased in developing countries, resulting in more
      severe hepatitis that is poorly understood mechanistically. More fundamentally,
      there is interest in comparing immunity to HAV and hepatitis C virus (HCV):
      small, positive-strand RNA viruses with very different infection outcomes. Here,
      we review evidence that circulating HAV virions are cloaked in membranes, with
      consequences for induction of innate immunity and antibody-mediated
      neutralization. We also consider the contribution of CD4+ helper versus CD8+
      cytotoxic T cells to antiviral immunity and liver injury, and present a model of
      non-cytotoxic immune control of HAV infection. 

PMID- 25617495
TI  - Repression of microRNA-130b by thyroid hormone enhances cell motility.
AB  - BACKGROUND & AIMS: Thyroid hormone (T3) and its receptor (TR) are involved in
      cell growth and cancer progression. Although deregulation of microRNA (miRNA)
      expression has been detected in many tumor types, the mechanisms underlying
      functional impairment and specific involvement of miRNAs in tumor metastasis
      remain unclear. In the current study, we aimed to elucidate the involvement of
      deregulated miRNA-130b (miR-130b) and its target genes mediated by T3/TR in
      cancer progression. METHODS: Quantitative reverse transcription-PCR, luciferase
      and chromatin immunoprecipitation assays were performed to identify the miR-130b
      transcript and the mechanisms implicated in its regulation. The effects of miR
      130b on hepatocellular carcinoma (HCC) invasion were further examined in vitro
      and in vivo. Clinical correlations among miR-130b, TRs and interferon regulatory
      factor 1 (IRF1) were examined in HCC samples using Spearman correlation analysis.
      RESULTS: Our experiments disclosed negative regulation of miR-130b expression by
      T3/TR. Overexpression of miR-130b led to marked inhibition of cell migration and
      invasion, which was mediated via suppression of IRF1. Cell migration ability was
      promoted by T3, but partially suppressed upon miR-130b overexpression.
      Furthermore, miR-130b suppressed expression of epithelial-mesenchymal transition
      (EMT)-related genes, matrix metalloproteinase-9, phosphorylated mammalian target
      of rapamycin (mTOR), p-ERK1/2, p-AKT and p-signal transducer and activator of
      transcription (STAT)-3. Notably, miR-130b was downregulated in hepatoma samples
      and its expression patterns were inversely correlated with those of TRalpha1 and
      IRF1. CONCLUSIONS: Our data collectively highlight a novel pathway interlinking
      T3/TR, miR-130b, IRF1, the EMT-related genes, p-mTOR, p-STAT3 and the p-AKT
      cascade, which regulates the motility and invasion of hepatoma cells.

PMID- 25617496
TI  - Epicardial fat in patients with non-alcoholic fatty liver disease.

PMID- 25617497
TI  - ECT2 regulates the Rho/ERK signalling axis to promote early recurrence in human
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Early recurrence is the major obstacle for improving the
      outcome of patients with hepatocellular carcinoma (HCC). Therefore, identifying
      key molecules contributing to early HCC recurrence can enable the development of
      novel therapeutic strategies for the clinical management of HCC. Epithelial cell
      transforming sequence 2 (ECT2) has been implicated in human cancers, but its
      function in HCC is largely unknown. METHODS: ECT2 expression was studied by
      microarrays, immunoblotting and immunohistochemistry in human HCC samples. siRNA-
      and lentiviral vector-mediated knockdown were employed to decipher the molecular
      functions of ECT2. RESULTS: The upregulation of ECT2 is significantly associated
      with early recurrent HCC disease and poor survival. Knockdown of ECT2 markedly
      suppressed Rho GTPases activities, enhanced apoptosis, attenuated oncogenicity
      and reduced the metastatic ability of HCC cells. Moreover, knockdown of ECT2 or
      Rho also suppressed ERK activation, while the silencing of Rho or ERK led to a
      marked reduction in cell migration. Stable knockdown of ECT2 in vivo resulted in
      significant retardation of tumour growth and the suppression of ERK activation.
      High expression of ECT2 correlates with high ERK phosphorylation and poor
      survival of HCC patients. Furthermore, ECT2 enhances the expression and stability
      of RACGAP1, accelerating ECT2-mediated Rho activation to promote metastasis.
      CONCLUSIONS: ECT2 is closely associated with the activation of the Rho/ERK
      signalling axis to promote early HCC recurrence. In addition, ECT2 can crosstalk
      with RACGAP1 to catalyse the GTP exchange involved in Rho signalling to further
      regulate tumour initiation and metastasis.

PMID- 25617498
TI  - Non-alcoholic fatty liver disease: severity of fibrosis and its relationships
      with clinical and biological variables.

PMID- 25617499
TI  - Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal
      endothelial cells enables control of autoimmunity in mice.
AB  - BACKGROUND & AIMS: It is well-known that the liver can induce immune tolerance,
      yet this knowledge could, thus far, not be translated into effective treatments
      for autoimmune diseases. We have previously shown that liver sinusoidal
      endothelial cells (LSECs) could substantially contribute to hepatic tolerance
      through their ability to induce CD4+ Foxp3+ regulatory T cells (Tregs). Here, we
      explored whether the Treg-inducing potential of LSECs could be harnessed for the
      treatment of autoimmune disease. METHODS: We engineered a polymeric nanoparticle
      (NP) carrier for the selective delivery of autoantigen peptides to LSECs in vivo.
      In the well-characterized autoimmune disease model of experimental autoimmune
      encephalomyelitis (EAE), we investigated whether administration of LSEC-targeting
      autoantigen peptide-loaded NPs could protect mice from autoimmune disease.
      RESULTS: We demonstrate that NP-based autoantigen delivery to LSECs could
      completely and permanently prevent the onset of clinical EAE. More importantly,
      in a therapeutic approach, mice with already established EAE improved rapidly and
      substantially following administration of a single dose of autoantigen peptide
      loaded NPs, whereas the control group deteriorated. Treatment efficacy seemed to
      depend on Tregs. The Treg frequencies in the spleens of mice treated with
      autoantigen peptide-loaded NPs were significantly higher than those in vehicle
      treated mice. Moreover, NP-mediated disease control was abrogated after Treg
      depletion by repeated administration of Treg-depleting antibody. CONCLUSION: Our
      findings provide proof of principle that the selective delivery of autoantigen
      peptides to LSECs by NPs can induce antigen-specific Tregs and enable effective
      treatment of autoimmune disease. These findings highlight the importance of Treg
      induction by LSECs for immune tolerance.

PMID- 25617502
TI  - Cell-autonomous decrease in proliferative competitiveness of the aged hepatocyte.
AB  - BACKGROUND & AIMS: The regenerative potential of the liver declines with age,
      this might be dependent on a decrease in the intensity of the stimulus and/or an
      increased refractoriness of the target. In the present study, we compared the in
      vivo growth capacity of young and old hepatocytes transplanted into the same
      host. METHODS: We utilized the retrorsine (RS)-based model for liver
      repopulation, which provides a specific and effective stimulus for transplanted
      hepatocytes. Rats of the dipeptidyl-peptidase type IV (DPP-IV)-deficient strain
      were given RS and were injected with a mix of hepatocytes isolated from either a
      2-month old or an 18-month old donor. To follow the fate of transplanted cells,
      they were each identified through a specific tag: young hepatocytes expressed the
      green fluorescent protein (GFP(+)), while those from old donors were DPP-IV
      positive. RESULTS: At 1 month post-transplantation, DPP-IV-positive clusters
      (derived from old donor) were consistently smaller than those GFP(+) (young
      donor); the cross sectional area of clusters was decreased by 50%, while the mean
      volume was reduced to 1/3. Furthermore, when 2/3 partial hepatectomy (PH) was
      performed, the S-phase response of old hepatocyte-derived clusters was only 30
      40% compared to that observed in cluster originating from young hepatocytes. No
      markers of cell senescence were expressed in clusters of transplanted
      hepatocytes. CONCLUSIONS: This is the first direct evidence in vivo that
      hepatocytes in the aged liver express a cell-autonomous decline in their
      replicative capacity and in their regenerative response to PH compared to those
      from a young animal.

PMID- 25617501
TI  - Epiplakin attenuates experimental mouse liver injury by chaperoning keratin
      reorganization.
AB  - BACKGROUND & AIMS: Epiplakin is a member of the plakin protein family and
      exclusively expressed in epithelial tissues where it binds to keratins. Epiplakin
      deficient (Eppk1(-/-)) mice displayed no obvious spontaneous phenotype, but their
      keratinocytes showed a faster keratin network breakdown in response to stress.
      The role of epiplakin in the stressed liver remained to be elucidated. METHODS:
      Wild-type (WT) and Eppk1(-/-) mice were subjected to common bile duct ligation
      (CBDL) or fed with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing
      diet. The importance of epiplakin during keratin reorganization was assessed in
      primary hepatocytes. RESULTS: Our experiments revealed that epiplakin is
      expressed in hepatocytes and cholangiocytes, and binds to keratin 8 (K8) and K18
      via multiple domains. In several liver stress models epiplakin and K8 genes
      displayed identical expression patterns and transgenic K8 overexpression resulted
      in elevated hepatic epiplakin levels. After CBDL and DDC treatment, Eppk1(-/-)
      mice developed a more pronounced liver injury and their livers contained larger
      amounts of hepatocellular keratin granules, indicating impaired disease-induced
      keratin network reorganization. In line with these findings, primary Eppk1(-/-)
      hepatocytes showed increased formation of keratin aggregates after treatment with
      the phosphatase inhibitor okadaic acid, a phenotype which was rescued by the
      chemical chaperone trimethylamine N-oxide (TMAO). Finally, transfection
      experiments revealed that Eppk1(-/-) primary hepatocytes were less able to
      tolerate forced K8 overexpression and that TMAO treatment rescued this phenotype.
      CONCLUSION: Our data indicate that epiplakin plays a protective role during
      experimental liver injuries by chaperoning disease-induced keratin
      reorganization.

PMID- 25617500
TI  - Prevalence of elevated ALT values, HBsAg, and anti-HCV in the primary care
      setting and evaluation of guideline defined hepatitis risk scenarios.
AB  - BACKGROUND & AIMS: Prevalence data for hepatitis B and C and an evaluation of a
      guideline based screening in the primary care setting are not yet available. We
      therefore implemented a hepatitis B surface antigen (HBsAg) and anti-hepatitis C
      virus (HCV) screening and developed guideline based screening strategies.
      METHODS: HBsAg, anti-HCV, and alanine aminotransferase (ALT) were included in a
      routine check-up together with a questionnaire covering 16 guideline adapted risk
      scenarios. Significant risk factors were identified by stepwise logistic
      regression. RESULTS: 51 private practices screened 21,008 patients. The HBsAg,
      anti-HCV, and HCV-RNA prevalence was 0.52%, 0.95%, and 0.43%, respectively.
      Infections were previously unknown in 85% and 65% of HBsAg and anti-HCV positive
      individuals, respectively. Sexual risk factors were under-reported, while the
      following scenarios were significantly associated with viral infections (Odds
      ratio [95% confidence interval]). HBV: Immigration (4.4 [2.9, 6.7]), infection in
      household (2.5 [1.2, 4.5]), male gender (1.6 [1.1, 2.4]). Male immigrants had a
      2.1% HBsAg prevalence and 80% were unaware of the infection. HCV: IV drug use
      (384 [233, 644]), blood transfusion before 1992 (5.3 [3.5, 7.9]), immigration
      (2.4 [1.5, 3.6]). Presence of either one of the HBV related guideline defined
      risk scenarios or elevated ALT identified 82% of previously undiagnosed patients.
      Presence of one of the three significant HCV risk factors or elevated ALT levels
      diagnosed 83% of unknown HCV-RNA positive cases by screening only 26% of the
      population. CONCLUSIONS: Undiagnosed hepatitis B and C infections frequently
      exist in the primary care setting. Easy to apply guideline defined risk scenarios
      help to diagnose previously unknown infections.

PMID- 25617503
TI  - Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile
      acid and lipid metabolism in morbid obesity.
AB  - BACKGROUND & AIMS: Bile acids (BAs) are major regulators of hepatic BA and lipid
      metabolism but their mechanisms of action in non-alcoholic fatty liver disease
      (NAFLD) are still poorly understood. Here we aimed to explore the molecular and
      biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross
      talk between liver and visceral white adipose tissue (vWAT) regarding BA and
      cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD
      patients. METHODS: In this randomized controlled pharmacodynamic study, we
      analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese
      patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to
      bariatric surgery. RESULTS: Short term UDCA administration stimulated BA
      synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X
      receptor (FXR) activation, resulting in cholesterol 7alpha-hydroxylase induction
      mirrored by elevated C4 and 7alpha-hydroxycholesterol. Enhanced BA formation
      depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme
      of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR
      anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the
      liver, thereby increasing hepatic triglyceride content. In addition, induced SCD
      activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic
      and more lipogenic monounsaturated fatty acids such as oleic acid. CONCLUSION:
      These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment
      in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces
      neutral lipid accumulation in both liver and vWAT.

PMID- 25617504
TI  - Disruption of a regulatory loop between DUSP1 and p53 contributes to
      hepatocellular carcinoma development and progression.
AB  - BACKGROUND & AIMS: Altered expression of dual specificity phosphatase 1 (DUSP1)
      is common in tumors including hepatocellular carcinoma (HCC), and is predictive
      of tumor progression and poor prognosis. However, the tumor suppressive role of
      DUSP1 has yet to be clearly elucidated. METHODS: The molecular mechanisms of
      tumor suppression that were investigated were induction of apoptosis, cell cycle
      inhibition, and regulation of p53. Additionally, the antitumor effect of DUSP1
      was assessed using a mouse model. Associated signaling pathways in HCC cells and
      tissues were examined. RESULTS: Downregulation of DUSP1 expression was
      significantly correlated with poor differentiation (p<0.001) and advanced HCC
      stage (p=0.023). DUSP1 expression resulted in HCC suppression and longer survival
      (p=0.0002) in a xenoplant mice model. DUSP1 inhibited p38 MAPK phosphorylation
      and subsequently suppressed HSP27 activation, resulting in enhanced p53
      phosphorylation at sites S15, S20, and S46 in HCC cells. Enhanced p53 activation
      induced the expression of target genes p21 and p27, which are linked to cell
      cycle arrest and apoptosis. Thus, DUSP1 was potentially linked to p53 activation
      via the p38 MAPK/HSP27 pathway. Wild-type but not mutant p53 transcriptionally
      upregulated DUSP1 via its DNA-binding domain. DUSP1 and p53 might collaborate to
      suppress tumors in hepatocarcinogenesis via a positive regulatory loop.
      CONCLUSIONS: Our results revealed that disruption of a positive regulatory loop
      between DUSP1 and p53 promoted HCC development and progression, providing a
      rationale for a therapeutic agent that restores DUSP1 in HCC.

PMID- 25617506
TI  - Hyperammonemia in ICU patients: a frequent finding associated with high
      mortality.

PMID- 25617505
TI  - Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac
      disease.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease is a common cause of chronic
      liver disease. Celiac disease alters intestinal permeability and treatment with a
      gluten-free diet often causes weight gain, but so far there are few reports of
      non-alcoholic fatty liver disease in patients with celiac disease. METHODS:
      Population-based cohort study. We compared the risk of non-alcoholic fatty liver
      disease diagnosed from 1997 to 2009 in individuals with celiac disease (n =
      26,816) to matched reference individuals (n = 130,051). Patients with any liver
      disease prior to celiac disease were excluded, as were individuals with a
      lifetime diagnosis of alcohol-related disorder to minimize misclassification of
      non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non
      alcoholic fatty liver disease were determined. RESULTS: During 246,559 person
      years of follow-up, 53 individuals with celiac disease had a diagnosis of non
      alcoholic fatty liver disease (21/100,000 person-years). In comparison, we
      identified 85 reference individuals diagnosed with non-alcoholic fatty liver
      disease during 1,488,413 person-years (6/100,000 person-years). This corresponded
      to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen
      in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after
      celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly
      elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5;
      95% CI 1.0-5.9). CONCLUSION: Individuals with celiac disease are at increased
      risk of non-alcoholic fatty liver disease compared to the general population.
      Excess risks were highest in the first year after celiac disease diagnosis, but
      persisted through 15 years after diagnosis with celiac disease.

PMID- 25617507
TI  - Efficacy of tranexamic acid on surgical bleeding in spine surgery: a meta
      analysis.
AB  - BACKGROUND CONTEXT: Spine surgery is usually associated with large amount of
      blood loss, necessitating blood transfusions. Blood loss-associated morbidity can
      be because of direct risks, such as hypotension and organ damage, or as a result
      of blood transfusions. The antifibrinolytic, tranexamic acid (TXA), is a lysine
      analog that inhibits activation of plasminogen and has shown to be beneficial in
      reducing surgical blood loss. PURPOSE: To consolidate the findings of randomized
      controlled trials (RCTs) investigating the use of TXA on surgical bleeding in
      spine surgery. STUDY DESIGN: A metaanalysis. STUDY SAMPLE: Randomized controlled
      trials investigating the effectiveness of intravenous TXA in reducing blood loss
      in spine surgery, compared with a placebo/no treatment group. METHODS: MEDLINE,
      Embase, Cochrane controlled trials register, and Google Scholar were used to
      identify RCTs published before January 2014 that examined the effectiveness of
      intravenous TXA on reduction of blood loss and blood transfusions, compared with
      a placebo/no treatment group in spine surgery. Metaanalysis was performed using
      RevMan 5. Weighted mean difference with 95% confidence intervals was used to
      summarize the findings across the trials for continuous outcomes. Dichotomous
      data were expressed as risk ratios with 95% confidence intervals. A p<.05 was
      considered statistically significant. RESULTS: Eleven RCTs were included for TXA
      (644 total patients). Tranexamic acid reduced intraoperative, postoperative, and
      total blood loss by an average of 219 mL ([-322, -116], p<.05), 119 mL ([-141, 
      98], p<.05), and 202 mL ([-299, -105], p<.05), respectively. Tranexamic acid led
      to a reduction in proportion of patients who received a blood transfusion (risk
      ratio 0.67 [0.54, 0.83], p<.05) relative to placebo. There was one myocardial
      infarction (MI) in the TXA group and one deep vein thrombosis (DVT) in placebo.
      CONCLUSIONS: Tranexamic acid reduces surgical bleeding and transfusion
      requirements in patients undergoing spine surgery. Tranexamic acid does not
      appear to be associated with an increased incidence of pulmonary embolism, DVT,
      or MI.

PMID- 25617510
TI  - Learning from others: international comparisons of death and dying.

PMID- 25617509
TI  - Manual segmentation qualification platform for the EADC-ADNI harmonized protocol
      for hippocampal segmentation project.
AB  - BACKGROUND: The use of hippocampal volumetry as a biomarker for Alzheimer's
      disease (AD) requires that tracers from different laboratories comply with the
      same segmentation method. Here we present a platform for training and qualifying
      new tracers to perform the manual segmentation of the hippocampus on magnetic
      resonance images (MRI) following the European Alzheimer's Disease Consortium and
      Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) Harmonized Protocol
      (HarP). Our objective was to demonstrate that the training process embedded in
      the platform leads to increased compliance and qualification with the HarP.
      METHOD: Thirteen new tracers' segmentations were compared with benchmark images
      with respect to: (a) absolute segmentation volume; (b) spatial overlap of contour
      with the reference using the Jaccard similarity index; and (c) spatial distance
      of contour with the reference. Point by point visual feedback was provided
      through three training phases on 10 MRI. Tracers were then tested on 10 different
      MRIs in the qualification phase. RESULTS: Statistical testing of training over
      three phases showed a significant increase of Jaccard (i.e. mean Jaccard overlap
      P < .001) between phases on average for all raters, demonstrating that training
      positively increased compliance with the HarP. Based on these results we defined
      qualification thresholds which all tracers were able to meet. CONCLUSIONS: This
      platform is an adequate infrastructure allowing standardized training and
      evaluation of tracers' compliance with the HarP. This is a necessary step
      allowing the use of hippocampal volumetry as a biomarker for AD in clinical and
      research centers.

PMID- 25617508
TI  - Comparison of mice with accelerated aging caused by distinct mechanisms.
AB  - Aging is the primary risk factor for numerous chronic, debilitating diseases.
      These diseases impact quality of life of the elderly and consume a large portion
      of health care costs. The cost of age-related diseases will only increase as the
      world's population continues to live longer. Thus it would be advantageous to
      consider aging itself as a therapeutic target, potentially stemming multiple age
      related diseases simultaneously. While logical, this is extremely challenging as
      the molecular mechanisms that drive aging are still unknown. Furthermore,
      clinical trials to treat aging are impractical. Even in preclinical models,
      testing interventions to extend healthspan in old age are lengthy and therefore
      costly. One approach to expedite aging studies is to take advantage of mouse
      strains that are engineered to age rapidly. These strains are genetically and
      phenotypically quite diverse. This review aims to offer a comparison of several
      of these strains to highlight their relative strengths and weaknesses as models
      of mammalian and more specifically human aging. Additionally, careful
      identification of commonalities among the strains may lead to the identification
      of fundamental pathways of aging. 

PMID- 25617511
TI  - "Frankly, my dear, I don't give a damn".
AB  - Four years ago, Michelle Holmes, Wendy Chen and collegues reported a significant
      negative correlation between aspirin use and breast cancer (Holmes et al. 2010).
      This summer, they noted that no randomized trials have been initiated that test
      this potentially important association. Why not? Pharmaceutical companies fund
      most drug research; there is no profit in aspirin. This explanation is
      incomplete. The deeper issue is a mismatch between the public interest in
      advancing research, and the interests of the institutions that governments
      subsidize in different ways for that purpose. In addition to patent protection,
      governments directly fund public granting agencies and provide the tax relief
      offered by private charities. Like pharmaceutical companies, these have their own
      "stakeholders" and objectives. Nobody, it appears, is interested in aspirin. 

PMID- 25617512
TI  - The drivers of overspending on prescription drugs in Quebec.
AB  - According to data from the most recent edition of the Canadian Rx Atlas, Quebec
      was the province with the highest total spending per capita on prescription
      drugs. The difference between Quebec and the rest of Canada was 35%, which
      translates into $1.5 billion dollars of extra spending. This analysis explores
      the economic cost drivers of the higher level of pharmaceutical spending in
      Quebec. While much of the additional spending was driven by a higher volume of
      drugs being prescribed overall, the factors contributing to higher spending
      differed greatly within particular therapeutic categories. The results and their
      implications are discussed in the context of pharmaceutical policy environment. 

PMID- 25617513
TI  - Supporting evidence-informed health policy making: the development and contents
      of an online repository of policy-relevant documents addressing healthcare
      renewal in Canada.
AB  - OBJECTIVES: (1) To develop an online repository of policy-relevant documents,
      other than and complementary to those from the peer-reviewed scientific
      literature, addressing healthcare renewal in Canada; and (2) to describe the
      distribution of document contents. METHODS: An iterative scoping review approach
      was undertaken. Documents were identified through website hand-searches and
      referrals from 19 Canadian health organizations. Descriptive frequencies were
      calculated, such as for document type. FINDINGS: In July 2014, 1," documents were
      in the Evidence-Informed Healthcare Renewal Portal. The top three types of
      documents were situation analyses (n = 390, 38%), health and health system data
      (n = 191, 18%) and jurisdictional reviews (n = 115, 11%). The top three national
      priority areas addressed were health human resources (n = 778, 75%), quality as a
      performance indicator (n = 502, 49%) and information technology (n = 385, 37%).
      CONCLUSION: The process of developing a systematic method for identifying these
      documents has yielded a new resource to support evidence-informed health policy
      making and has identified a large volume of policy-relevant documents addressing
      healthcare renewal priority areas in Canada.

PMID- 25617514
TI  - Choosing your partner for the PROM: a review of evidence on patient-reported
      outcome measures for use in primary and community care.
AB  - Patient-reported outcome measures (PROMs) are assessments of health status from
      the patient's perspective. The systematic and routine collection and use of PROMs
      in healthcare settings adds value in several ways, including quality improvement
      and service evaluation. We address the issue of instrument selection for use in
      primary and/or community settings. Specifically, from the large number of
      available PROMs, which instrument delivers the highest level of performance and
      validity? For selected generic PROMs, we reviewed literature on psychometric
      properties and other instrument features (e.g., health domains captured). Briefly
      we summarize key strengths of the three PROMs that received the most favourable
      psycho-metric and overall evaluation. The Short-Form 36 has a number of
      strengths, chiefly, its strong psychometric properties such as responsiveness.
      The PROMIS/Global Health Scale scored highly on most criteria and warrants
      serious consideration, especially as it is free to use. The EQ-5D scored
      satisfactorily on many criteria and, beneficially, it has a low response burden. 

PMID- 25617515
TI  - The primary-specialty care interface in chronic diseases: patient and practice
      characteristics associated with co-management.
AB  - OBJECTIVE: Specialist physicians may act either as consultants or co-managers for
      patients with chronic diseases along with their primary healthcare (PHC)
      physician. We assessed factors associated with specialist involvement. METHODS:
      We used questionnaire and administrative data to measure co-management and
      patient and PHC practice characteristics in 702 primary care patients with common
      chronic diseases. Analysis included multilevel logistic regressions. RESULTS: In
      all, 27% of the participants were co-managed. Persons with more severe chronic
      diseases and lower health-related quality of life were more likely to be co
      managed. Persons who were older, had a lower socioeconomic status, resided in
      rural regions and who were followed in a PHC practice with an advanced practice
      nurse were less likely to be co-managed. DISCUSSION: Co-management of patients
      with chronic diseases by a specialist is associated with higher clinical needs
      but demonstrates social inequalities. PHC practices more adapted to chronic care
      may help optimize specialist resources utilization.

PMID- 25617516
TI  - Understanding the research-policy divide for oral health inequality.
AB  - BACKGROUND: No studies exist of the congruence of research in oral health to
      policy. This study aimed to examine the broad congruence of oral health research
      to policy, and implications for developing oral health research that is more
      policy relevant, particularly for the wider challenge of addressing unequal oral
      health outcomes, rather than specific policy translation issues. METHODS:
      Bayesian-based software was used in a multi-layered method to compare the
      conceptual content of 127,193 oral health research abstracts published between
      2000-2012 with eight current oral health policy documents from Organisation for
      Economic Co-operation and Development countries. FINDINGS: Fifty-five concepts
      defined the research abstracts, of which only eight were policy-relevant, and six
      of which were minor research concepts. CONCLUSIONS: The degree of disconnection
      between clinical concepts and healthcare system and workforce development
      concepts was striking. This study shows that, far from being "lost in
      translation," oral health research and policy are so different as to raise doubts
      about the extent to which research is policy-relevant and policy is research
      based. The notion of policy relevance encompasses the lack of willingness of
      policy makers to embrace research, and the need for researchers to develop
      research that is, and is seen to be, policy-relevant.

PMID- 25617517
TI  - [Three types of brand name loyalty strategies set up by drug manufacturers].
AB  - The recent restructuring of the pharmaceutical industry has led to three new
      types of promotional strategies to build patient loyalty to brand name drugs:
      loyalty through rebates, patient support, and compassion programs. Loyalty
      through rebates seeks to keep patients on a brand name drug and prevent their
      switch to the generic equivalent. Loyalty through patient support provides
      aftersales services to help and support patients (by phone or home visits) in
      order to improve adherence to their treatments. Finally, compassion programs
      offer patients access to drugs still awaiting regulatory approval or
      reimbursement by insurers. When and if the approval process is successful, the
      manufacturer puts an end to the compassion program and benefits from a
      significant cohort of patients already taking a very expensive drug for which
      reimbursement is assured. The impact of these programs on public policies and
      patients' rights raises numerous concerns, among which the direct access to
      patients and their health information by drug manufacturers and upward pressure
      on costs for drug insurance plans.

PMID- 25617518
TI  - Biogenesis of mitochondria in cauliflower (Brassica oleracea var. botrytis) curds
      subjected to temperature stress and recovery involves regulation of the
      complexome, respiratory chain activity, organellar translation and
      ultrastructure.
AB  - The biogenesis of the cauliflower curd mitochondrial proteome was investigated
      under cold, heat and the recovery. For the first time, two dimensional
      fluorescence difference gel electrophoresis was used to study the plant
      mitochondrial complexome in heat and heat recovery. Particularly, changes in the
      complex I and complex III subunits and import proteins, and the partial
      disintegration of matrix complexes were observed. The presence of unassembled
      subunits of ATP synthase was accompanied by impairment in mitochondrial
      translation of its subunit. In cold and heat, the transcription profiles of
      mitochondrial genes were uncorrelated. The in-gel activities of respiratory
      complexes were particularly affected after stress recovery. Despite a general
      stability of respiratory chain complexes in heat, functional studies showed that
      their activity and the ATP synthesis yield were affected. Contrary to cold
      stress, heat stress resulted in a reduced efficiency of oxidative phosphorylation
      likely due to changes in alternative oxidase (AOX) activity. Stress and stress
      recovery differently modulated the protein level and activity of AOX. Heat stress
      induced an increase in AOX activity and protein level, and AOX1a and AOX1d
      transcript level, while heat recovery reversed the AOX protein and activity
      changes. Conversely, cold stress led to a decrease in AOX activity (and protein
      level), which was reversed after cold recovery. Thus, cauliflower AOX is only
      induced by heat stress. In heat, contrary to the AOX activity, the activity of
      rotenone-insensitive internal NADH dehydrogenase was diminished. The relevance of
      various steps of plant mitochondrial biogenesis to temperature stress response
      and recovery is discussed. 

PMID- 25617519
TI  - Low-dose Nociceptin/Orphanin FQ reduces anxiety-like performance in alcohol
      withdrawn, but not alcohol-naive, Male Wistar rats.
AB  - Alcohol withdrawal is associated with neuroadaptation of stress-regulatory
      systems, including transmission of neuropeptides that have been implicated in
      anxiety-like performance. Nociceptin/Orphanin FQ (N/OFQ), an endogenous
      neuropeptide ligand at the NOP receptor, has been implicated in stress and has
      previously been shown to attenuate or exacerbate anxiety-like performance in rats
      following a biphasic dose response function. In addition, divergent actions on
      anxiety-like performance have been observed in alcohol-withdrawn vs. control
      animals, suggesting alcohol-induced alteration of N/OFQ transmission. In order to
      differentiate between whether this divergence resulted from a "switch" in the
      actions of N/OFQ vs. increased sensitivity in N/OFQ transmission, we assessed the
      actions of low doses of N/OFQ (0, 0.125, 0.25, or 0.5 MUg) on two tests of
      anxiety, the shock-probe defensive burying and elevated plus maze tests, three
      weeks after the termination of a six-day regimen of alcohol or vehicle
      administration via intragastric intubation. Consistent with increased sensitivity
      in N/OFQ resulting from a history of alcohol intake, administration of a low dose
      of N/OFQ (0.25 MUg) selectively attenuated anxiety-like behaviors in animals with
      a history of alcohol intake while controls did not exhibit any changes in
      performance. The present results suggest that withdrawal from alcohol produces an
      enduring increase in sensitivity in N/OFQ transmission - a finding that is
      consistent with previous studies demonstrating altered transmission in related
      neuropeptide systems. 

PMID- 25617520
TI  - Polymorphisms in inhibin alpha gene promoter associated with male infertility.
AB  - Inhibins play important roles in normal gonadal function, including regulation of
      proliferation, differentiation, and steroidogenesis of Leydig and Sertoli cells
      via paracrine and autocrine processes. In adult males, circulating inhibin levels
      are correlated with fertility by regulating the number of Sertoli cells, total
      sperm count, and testicular volume. Given this important role, inhibin-alpha
      subunit (INHA) is a strong candidate gene in male fertility. However, limited
      data regarding the association of polymorphisms of INHA with male fertility are
      available. This study was based on the hypothesis that polymorphisms in the
      promoter of INHA are associated with male fertility. Han Chinese patients with
      non-normozoospermia (n=153) and normozoospermia (n=72) from Northern China were
      screened, and genotypes were analyzed by polymerase chain reaction-restriction
      fragment length polymorphism after INHA promoter was amplified. Statistical
      analysis results revealed a significant difference in the allele frequency of
      INHA promoter between males with non-normozoospermia and normozoospermia. For c.
      124G>A, males carrying c.-124GG genotype and c.-124GA genotype showed an
      increased risk of non-normozoospermic syndrome. For c.-16C>T polymorphism, no
      significant difference in allele frequency was observed between the two groups.
      Therefore, the haplotype AC possibly displayed a considerable reduced risk of non
      normozoospermic syndrome. 

PMID- 25617521
TI  - Co-occurrence of mosaic supernumerary isochromosome 18p and intermittent 2q13
      deletions in a child with multiple congenital anomalies.
AB  - The present study deals with karyotpye-phenotype correlations in a six month old
      child with multiple congenital abnormalities. Cytogenetic analysis revealed
      mosaicism of a small metacentric supernumerary marker chromosome with a karyotype
      mos 47,XY+mar[34]/46,XY[31]. Cytogenetic microarray result showed three copies of
      chromosome 18p (15,400 kb in size). Moreover, 255 kbp intermittent deletion of
      chromosome 2q13 involving RGPD5, RGPD6, LIMS3, and LIMS3-LOC440895 was also
      observed. Correlating microarray data with the mosaic karyotype, the marker
      chromosome was identified as mosaic isochromosome 18p and was found to be 32,600
      kbp in size. Baby resembled clinical characteristics of trisomy chromosome 18p,
      isochromosome 18p and trisomy chromosome 18. The present study suggested that
      deletion of evolutionarily conserved developmental genes (RGPD5, RGPD and LIMS3)
      in the 2q13 region might have contributed to more severity in phenotype as
      compared to so far such reported cases of 18p trisomy's, as these are involved in
      nuclear-cytoplasm trafficking, signaling for tissue patterning and
      differentiation.

PMID- 25617522
TI  - Transposable element-driven transcript diversification and its relevance to
      genetic disorders.
AB  - The human genome project and subsequent gene annotation projects have shown that
      the human genome contains 22,000-25,000 functional genes. Therefore, it is
      believed that the diversity of protein repertoire is achieved by the alternative
      splicing (AS) mechanism. Transposable elements (TEs) are mobile in nature and can
      therefore alter their position in the genome. The insertion of TEs into a new
      gene region can result in AS of a particular transcript through various
      mechanisms, including intron retention, and alternative donor or acceptor splice
      sites. TE-derived AS is thought to have played a part in primate evolution and in
      hominid radiation. However, TE-derived AS or genetic instability may sometimes
      result in genetic disorders. For the past two decades, numerous studies have been
      performed on TEs and their role in genomes. Accumulating evidence shows that the
      term 'junk DNA', previously used for TEs is a misnomer. Recent research has
      indicated that TEs may have clinical potential. However, to explore the
      feasibility of using TEs in clinical practice, additional studies are required.
      This review summarizes the available literature on TE-derived AS, alternative
      promoter, and alternative polyadenylation. The review covers the effects of TEs
      on coding genes and their clinical implications, and provides our perspectives
      and directions for future research. 

PMID- 25617523
TI  - Type I interferon receptors in goose: molecular cloning, structural
      identification, evolutionary analysis and age-related tissue expression profile.
AB  - The cDNAs encoding two distinct type I interferon receptors were firstly cloned
      from the spleen of white goose (the Chinese goose, Anser cygnoides). The cDNA of
      goose IFNAR1 consisted of 1616 bp and encoded 406 amino acids with a predicted
      molecular weight of 46.4 kDa, while the cDNA of goose IFNAR2 consisted of 1525 bp
      and encoded 294 amino acids with a predicted molecular weight of 32.6 kDa. The
      IFNAR1 shared 85.4% identity in deduced amino acid sequence with duck IFNAR1,
      while IFNAR2 amino acid sequence showed 86% identity with that of duck IFNAR2.
      The age-related analysis of gene expression revealed that goose IFNalpha and
      IFNARs were all highly transcribed in pancreas, which may due to a reasonable
      amount of dendritic cells aggregated in pancreas. And goose IFNalpha and its
      cognate receptors had different structural features and tissue expression
      patterns during the period from embryonic goose to adult goose, suggesting that
      IFNalpha and IFNARs may maintain a developmental dynamic immune competence in
      unstimulated states. The data provided in this study may contribute to future
      understanding of the interaction between interferon and interferon receptors in
      immune mechanism. And it also helps us to understand the age-related
      susceptibility to pathogens in birds better.

PMID- 25617524
TI  - Analysis of differential gene expression under low-temperature stress in Nile
      tilapia (Oreochromis niloticus) using digital gene expression.
AB  - Tilapia (Oreochromis niloticus) do not survive well at low temperatures.
      Therefore, improvement of the low-temperature resistance has become an important
      issue for aquaculture development of tilapia. The objective of this study was to
      construct a digital gene expression tag profile to identify genes potentially
      related to low temperature in tilapia. In this study, tilapia was treated at 30
      degrees C to lethal temperature 10 degrees C in decrement of 1 degrees CD(-1).
      Digital gene expression analysis was performed using the Illumina technique to
      investigate differentially expressed genes in tilapia cultured at different
      temperatures (30 degrees C, 26 degrees C, 20 degrees C, 16 degrees C, and 10
      degrees C). A total of 206,861, 188,082, 185,827, 188,067, and 214,171 distinct
      tags were obtained by sequencing these five libraries, respectively. Compared
      with the 30 degrees C library, there were 304, 407, 709, and 772 upregulated
      genes and 342, 793, 771, and 1466 downregulated genes in 26 degrees C, 20 degrees
      C, 16 degrees C, and 10 degrees C libraries, respectively. Trend analysis of
      these differentially expressed genes identified six statistically significant
      trends. Functional annotation analysis of the differentially expressed genes
      identified various functions associated with the response to low-temperature
      stress. When tilapia are subjected to low-temperature stress, expression changes
      were observed in genes associated with nucleic acid synthesis and metabolism,
      amino acid metabolism and protein synthesis, lipid and carbohydrate content and
      types, material transport, apoptosis, and immunity. The differentially expressed
      genes obtained in this study may provide useful insights to help further
      understand the effects of low temperature on tilapia.

PMID- 25617525
TI  - Estrogen receptor alphalpha gene (ESR1) PvuII and XbaI polymorphisms are
      associated to metabolic and proinflammatory factors in polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that
      involves multiple factors. Although the etiology of PCOS is unknown, there is an
      involvement of sex steroid hormones in the pathophysiology of this syndrome.
      Therefore, polymorphisms in genes involved in the action of estrogen may
      contribute to a woman's susceptibility to PCOS. AIM: This study aimed to evaluate
      the association between the polymorphisms PvuII and XbaI in the estrogen receptor
      alpha (ESR1) gene and the occurrence of PCOS. The study also aimed to assess the
      influence of these polymorphisms on the metabolic and inflammatory profiles of
      women with PCOS. MATERIAL AND METHODS: This case-control study included 99 women
      with PCOS, diagnosed according to the Rotterdam criteria, and 104 age-matched
      healthy women. The polymorphisms were evaluated using polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: No association between the
      ESR1 gene polymorphisms and the presence of PCOS was observed. However, we found
      associations between the PvuII polymorphism and C-reactive protein levels,
      testosterone levels, family history of diabetes, and waist circumference. The
      XbaI polymorphism was associated with fasting glucose and a family history of
      hypertension. CONCLUSION: These polymorphisms are not associated with PCOS
      development, but they are involved in the phenotype of complications of the
      syndrome. Therefore, prior knowledge of these genomic variants might contribute
      to taking preventive measures that could delay the metabolic and reproductive
      complications commonly seen in women with PCOS.

PMID- 25617526
TI  - Processes discriminating adaptive and maladaptive Internet use among European
      adolescents highly engaged online.
AB  - Today adolescents are highly engaged online. Contrary to common concern, not all
      highly engaged adolescents develop maladaptive patterns of internet use. The
      present qualitative study explored the experiences, patterns and impact of use of
      124 adolescents (M(age) = 16.0) reporting signs of internet addictive behaviors.
      The focus was to discern adaptive and maladaptive use patterns, which promote or
      interfere with adolescents' development, respectively. Semi-structured individual
      interviews were conducted in seven European countries (Greece, Spain, Poland,
      Germany, Romania, Netherlands and Iceland) and qualitatively analyzed using
      grounded theory. Considerable variability emerged in the way adolescents
      satisfied their personal needs online and offline, in the experienced impact from
      high online engagement and functional value ascribed to the internet, and in the
      self-regulatory processes underlying use. Variability in these discriminating
      processes was linked to adaptive or maladaptive adolescent internet use patterns.
      The emerged processes can provide direction for designing prevention and
      intervention programs promoting adaptive use.

PMID- 25617527
TI  - Clinical implication of leucine zipper/EF hand-containing transmembrane-1
      overexpression in the prognosis of triple-negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is a heterogeneous disease with higher rates
      of relapse and decreased overall survival in metastatic tumors. Due to its poor
      prognosis, it is necessary to identify effective biomarkers that are associated
      with tumor growth and metastasis. The leucine zipper/EF hand-containing
      transmembrane-1 (LETM1) protein, which is a mitochondrial inner membrane protein,
      can reduce mitochondrial biogenesis and ATP production. The expression levels of
      LETM1 were significantly increased in numerous human malignancies. However, the
      clinicopathological characteristics and prognostic value of LETM1 overexpression
      in TNBC remains unclear. LETM1 protein was detected in 107 TNBC, 42 ductal
      carcinoma in situ (DCIS) and 65 adjacent non-tumor breast tissues using
      immunohistochemical (IHC) staining. Immunofluorescence (IF) staining was also
      performed to detect the localization of LETM1 protein in MCF-7 BC cells. The
      correlations between LETM1 overexpression and clinicopathological features of
      TNBC were evaluated using Chi-squared test and Fisher's exact tests. The survival
      rate was calculated using the Kaplan-Meier method. LETM1 protein showed
      cytoplasmic staining patterns in TNBC. The strongly positive rate of LETM1 in
      TNBC was 69.2% (74/107), which was significantly higher than in both DCIS 35.7%
      (15/42) and adjacent non-tumor tissues 12.3% (8/65). High-level expression of
      LETM1 was positively correlated with late clinical stage, poor differentiation,
      lymph node metastasis, disease-free survival (DFS) and 10-year overall survival
      (OS) rates in TNBC. Further analysis showed that high LETM1 expression along with
      clinical stage emerged as significant independent risk factors in patients with
      TNBC. In conclusion, LETM1 protein overexpression is associated with TNBC
      progression, and may be a potential biomarker for poor prognostic evaluation of
      TNBC. 

PMID- 25617528
TI  - Downregulation of HTATIP2 expression is associated with promoter methylation and
      poor prognosis in glioma.
AB  - Glioma is an aggressive tumor with poor prognosis. Identification of precise
      prognostic marker and effective therapeutic target is important in the treatment
      of glioma. HTATIP2 is a novel tumor suppressor gene, which is frequently silenced
      by epigenetic mechanisms in many caners. However, the expression of HTATIP2 and
      how it is regulated in glioma are unknown. Hence, we assessed whether loss of
      HTATIP2 expression occurs in glioma, and, if so, what is the mechanism of such
      loss. We found that HTATIP2 expression was absent or diminished in primary
      gliomas compared with normal brain tissue. In vitro experiments showed that
      HTATIP2 expression could be restored via 5-aza-2'deoxycytidine treatment in U87
      and U251 cell lines. Methyl-specific PCR indicated that the two cell lines and
      60% primary gliomas carried aberrant methylated HTATIP2 alleles while normal
      brain tissue did not. Pyrosequencing confirmed these results and showed a higher
      density of methylation in the minimal promoter element, which contains four Sp1
      binding sites in primary gliomas, than in normal brain tissue. Finally, we found
      that the overall survival was significantly higher in patients with positive
      HTATIP2 expression than those with loss of HTATIP2 expression. Overexpression of
      HTATIP2 inhibited glioma proliferation and growth in vitro. Taken together, the
      present study showed that loss of HTATIP2 expression was a frequent event in
      glioma and is associated with poor prognosis. Promoter methylation may be an
      underlying mechanism. 

PMID- 25617529
TI  - Hemispheric asymmetries and the control of motor sequences.
AB  - Sequencing of finger positions reflects a prototype of skilled behaviour. In
      order to perform sequencing, cognitive control supports the requirements and
      postural transitions. In this electroencephalography (EEG) study, we evaluate the
      effects of hand dominance and assess the neural correlates of unimanual and
      bimanual sequencing in left- and right-handers. The behavioural measurements
      provided an index of response planning (response time to first key press) and
      response execution (time between successive key presses, taps/s and percentage of
      correct responses), whereas the neural dynamics was determined by means of EEG
      coherence, expressing the functional connectivity between brain areas.
      Correlations between brain activity and behaviour were calculated for exploring
      the neural correlates that are functionally relevant for sequencing. Brain
      behavioural correlations during response planning and execution revealed the
      significance of circuitry in the left hemisphere, underlining its significant
      role in the organisation of goal-directed behaviour. This lateralisation profile
      was independent of intrinsic constraints (hand dominance) and extrinsic demands
      (task requirements), suggesting essential higher-order computations in the left
      hemisphere. Overall, the observations highlight that the left hemisphere is
      specialised for sequential motor organisation in left- and right-handers,
      suggesting an endogenous hemispheric asymmetry for compound actions and the
      representation of skill; processes that can be separated from those that are
      involved in hand dominance.

PMID- 25617530
TI  - Differential effects of oxycodone, hydrocodone, and morphine on the responses of
      D2/D3 dopamine receptors.
AB  - Oxycodone and hydrocodone are opioids which are widely used for pain management
      and are also commonly misused and abused. The exposure to opioid analgesics has
      been associated with altered responses of D2-like dopamine receptors (D2DRs). Our
      recent results suggest that various opioids will differentially modulate the
      responses of D2DRs. The D2DRs are known to be involved in the pathology of
      addiction and other mental illnesses, indicating the need to improve our
      understanding of the effects of opioid analgesics on the responses of the D2DRs.
      Thus, in this study, we first established equianalgesic oral doses of oxycodone,
      hydrocodone, and morphine using the tail withdrawal assay. Then, mice were orally
      administered (gavage) with the various opioids or saline once daily for 6 days.
      Twenty-four hours later, the mice were tested for their locomotor response to
      quinpirole, a D2/D3 dopamine receptor agonist. Mice pretreated with oxycodone
      showed significantly greater locomotor supersensitivity to quinpirole than did
      morphine-pretreated mice, while hydrocodone-pretreated mice showed sensitivity in
      between that of mice treated with morphine and oxycodone. This finding suggests
      that various opioids differentially modulate the responses of D2DRs. It provides
      further evidence supporting of the notion that various opioids carry differential
      risks to the dopamine reward system. 

PMID- 25617531
TI  - Steroidogenesis and phase II conjugation during the gametogenesis of thicklip
      grey mullet (Chelon labrosus) from a population showing intersex condition.
AB  - Steroidogenesis, the process by which steroid hormones are synthesized, involves
      a vast number of enzymes and biochemical pathways that are susceptible to
      chemical modulation. Endocrine disrupting compounds (EDCs) are of special concern
      since they can alter hormone homeostasis by interfering with synthesis, transport
      and elimination of hormones. It is important to understand gender differences and
      the natural variation in steroid balance through gamete development in fish
      exposed to EDCs. The aim of this study was to determine mRNA levels of genes
      encoding for Steroidogenic Acute Regulatory (star) protein; the steroidogenic
      enzymes P450 11beta hydroxylase (cyp11b1) and P450 aromatase (cyp19a1a); as well
      as the phase II conjugation enzymes sulfotransferase (sult) and UDP
      glucuronosyltransferase (ugt), together with the activity of P450 aromatase and
      plasma levels of 17beta-estradiol (E2) and 11-ketotestosterone (11-KT), at
      different gametogenic stages and in intersex individuals of the thicklip grey
      mullet Chelon labrosus. Results demonstrated that the transcription levels of
      star, sult and ugt and levels of E2 and 11-KT in plasma significantly changed
      with the interaction between gender and reproductive stage. Cyp11b1 and cyp19a1a
      transcription levels were significantly different between genders while the
      activity of P450 aromatase varied significantly between genders and reproductive
      stages. Results from a multivariate assessment demonstrated that measured
      endpoints distinguished male, female and intersex mullets at immature gametogenic
      stage. Intersex distinction was based on sult, ugt and cyp19a1a transcript levels
      and P450 aromatase activity. The present work provides data to be used in future
      experimental designs with C. labrosus species, and gives new clues about the
      molecular events that lead to intersex occurrence in mullets. 

PMID- 25617532
TI  - [Fifth Jesus Culebras Lecture; Tree nuts: effects on health, obesity and
      metabolic syndrome].
AB  - Several epidemiological studies have shown that consumption of tree nuts is
      associated with lower cardiovascular risk, specific cause of mortality and total
      mortality. Clinical feeding trials have demonstrated that tree nuts protect from
      cardiovascular disease risk through different mechanisms: regulating inflammatory
      processes, oxidative stress and endothelial function, thereby improving various
      cardiovascular risk factors. In the context of meals high in carbohydrates, tree
      nuts reduce the postprandial glucose peaks, improving insulin resistance.
      Frequent consumption of nuts has been associated with a lower risk of diabetes in
      women, but the effect was not yet elucidated in men. Although tree nuts are
      energetically dense and they are high in fat, nut consumption does not imply
      appreciable weight gain nor has been associated with a higher risk of abdominal
      obesity. Tree nut consumption reduces LDL cholesterol levels, but its effects on
      atherogenic dyslipidemia associated to metabolic syndrome (MetS) are less clear.
      The effect of consumption of nuts on LDL cholesterol in subjects with MetS
      neither has been well established, but it seems that in these patients could
      lower plasma triglyceride levels. Some studies suggest an inverse association
      between tree nut consumption and blood pressure or endothelial function,
      especially in non-diabetic individuals. Nut consumption was inversely related to
      the prevalence and incidence of MetS. Including tree nuts in the context of a
      healthy dietary pattern way increase the health benefits. It has been observed a
      lower prevalence of MetS and a lower incidence of diabetes in people who adhered
      to a Mediterranean diet supplemented with nuts. Future nutrition intervention
      studies are needed on large samples of subjects and long follow-up to affirm that
      tree nut consumption has beneficial effects on the prevention and treatment of
      MetS. 

PMID- 25617533
TI  - Mechanisms used by inulin-type fructans to improve the lipid profile.
AB  - AIMS: The consumption of prebiotics has been associated with improvement in the
      lipid profile. Thus, this review aims to describe the main mechanisms by which
      inulin-type fructans improve the lipid profile and thereby reduce the
      cardiovascular risk. DATA SYNTHESIS: Inulin-type fructans have been demonstrated
      to improve the lipid profile through a number of mechanisms. These mechanisms
      include: decrease in gene expression of hepatic enzymes responsible for de novo
      synthesis of lipids; increase of muscle lipoprotein lipase enzyme activity,
      enhancing the production of short-chain fatty acids; altered production of
      polyamines which increases the production of satiogenic peptide; altered blood
      glucose and insulinemia; increase of fecal excretion of bile salts and
      cholesterol and increase of the Bifidobacterium population. CONCLUSIONS: The
      consumption of inulin-type fructans enhances lipid profile. Generally, the
      mechanisms vary according to the physiologic state of the individual and the type
      of diet to which the inulin-type fructans are added. Thus, inulin may be used for
      the prevention and/or treatment of cardiovascular diseases.

PMID- 25617534
TI  - [Effects of wine polyphenols on cancer prevention].
AB  - INTRODUCTION: Cancer has become in the recent decades one of the leading causes
      of death worldwide. The search for effective prevention has become a priority for
      the basic and clinical science. Wine polyphenols have been proposed as
      alternative therapy for induction and on maintaining remission of cancer.
      OBJECTIVE: To review current scientific evidence of cancer and the efficacy of
      dietary supplement therapy (especially wine polyphenols). MATERIALS AND METHODS:
      Extensive search of scientific publications was performed in specialized
      electronic databases: NBCI, Elsevier, Scielo, Scirus and Science Direct. RESULTS
      AND DISCUSSION: Results from in vitro and laboratory animals experiments
      demonstrate that wine polyphenols controls the cell apoptosis of different type
      of cancers through out the increase of reactive oxygen species, and decrease of
      cell growth. Different studies have shown that regular and moderate wine
      consumption (one or two glasses for day) is associated with decreased incidence
      of cardiovascular disease, hypertension, diabetes, and certain cancers, such as
      colon, breast, lung, or prostate. However, more scientific evidences are needed
      to strength the effect of resveratrol in controlling cancer. CONCLUSIONS: A
      better knowledge and understanding of the wine polyphenol role in cancer disease
      patients is possible with the current published results. The wine polyphenols
      plays a significant role as antioxidant and prooxidant in cancer, although more
      extensive studies are required to determine the clinical significance in humans.

PMID- 25617535
TI  - Review of complementary feeding practices in Mexican children.
AB  - BACKGROUND: The early introduction of food is consistent with a significant
      increase in the prevalence of overweight and obesity, particularly in children,
      partly because of the resulting changes in feeding patterns. The purpose of this
      study was to describe the complementary feeding practices of Mexican children
      younger than two years of age. METHODS: Medline, Lilacs and manual methods were
      used to search for studies that assessed feeding practices in children younger
      than two years of age in Mexico. The following terms were used: complementary
      feeding, supplementary feeding, Mexico and weaning. Data on complementary feeding
      practices, including the age of initiation, the type of foods eaten, the
      frequency of food intake and the reasons for starting complementary feeding, were
      collected. The information gathered was subjected to qualitative analysis, and
      the data are presented as proportions in the tables. RESULTS: The seven studies
      included in this evaluation revealed that children were introduced to
      complementary feeding before the age of 6 months. Although fruits were the foods
      most commonly provided when complementary feeding began, processed juices, soft
      drinks and fried snacks were also offered. The intake of these products increased
      as the children grew older and coincided with a low intake of foods containing
      high-biological value protein, particularly red meats. CONCLUSIONS: The results
      of the included studies showed that during complementary feeding, infants receive
      high-energy density foods, whereas the intake of foods that provide animal
      protein and iron in particular is low. In addition, common conditions associated
      with complementary feeding include overweight, obesity, malnutrition, and anemia,
      which may contribute to health problems.

PMID- 25617536
TI  - Clinical and molecular evidence of the consumption of broccoli, glucoraphanin and
      sulforaphane in humans.
AB  - INTRODUCTION: Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin
      (GRA), which is found in great amounts especially in broccoli. Its consumption
      has been reported to be associated with a lower risk of myocardial infarction and
      cancer development. Additionally, its effects have been studied in
      neurodegenerative diseases, diabetes, and atherosclerosis, most of the times
      using animal models and cell cultures. OBJECTIVES: Given the promising results of
      SFN, this review aimed to investigate evidence documented in human intervention
      studies with broccoli, GRA and SFN. METHODS: A search was performed on PubMed and
      Virtual Health Library databases by two independent researchers using the
      descriptors "broccoli" or "glucoraphanin" or "sulforaphane", which should appear
      on the study's title or abstract. This review included randomized clinical trials
      performed in humans that were published in English and Portuguese from 2003 to
      2013 and that considered clinical and molecular parameters of cell damage as
      outcomes of interest. RESULTS: Seventeen studies were selected, and the
      predominant type of intervention was broccoli sprouts. More consistent results
      were obtained for the clinical parameters blood glucose and lipid profile and for
      molecular parameters of oxidative stress, indicating that there was an
      improvement in these parameters after intervention. Less solid evidence was found
      with regard to decreased inflammation, Helicobacter pylori colonization, and
      protection against cancer. CONCLUSION: Although being relevant, the evidence for
      the use of broccoli, GRA and SFN in humans are limited; thus, further
      intervention studies are needed to evaluate outcomes more consistently and reach
      better grounded conclusions.

PMID- 25617537
TI  - Safety in the hypertriglyceridemia treatment with N-3 polyunsaturated fatty acids
      on glucose metabolism in subjects with type 2 diabetes mellitus.
AB  - INTRODUCTION: Type 2 diabetes mellitus increases the risk of hypertriglyceridemia
      and is an independent risk factor for cardiovascular diseases. Current literature
      reveals the beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFA) in
      hypertriglyceridemia treatment, however the safety for type 2 diabetic subjects
      are still debatable. This literature review discusses the safety on glucose
      metabolism of n-3 PUFA supplementation in the treatment of hypertriglyceridemia
      in subjects with type 2 diabetes mellitus. METHODS: A literature review was
      conducted on EMBASE and MEDLINE database to investigate clinical trials published
      since 1990 until June 2014 that investigated the effects of
      dietary/supplementation n-3 PUFA intake in hypertriglyceridemia treatment in
      subjects with type 2 diabetes mellitus. RESULTS AND DISCUSSION: Fourteen clinical
      trials (n = 2,105) were included in this review. All trials reported a reduction
      in triglycerides levels between 12 - 34% in intra- group and 15 - 36% in between
      groups analysis. Four trials showed a significant increase in LDL-c (6 - 18%) and
      another four in HDL-c levels (4 - 15%). No significant changes were found to
      total cholesterol, VLDL-c, fasting glucose, HbA1C, and insulin sensitivity index.
      CONCLUSIONS: The n-3 PUFA supplementation leads an improvement on TG levels and
      did not result in any impairment on glucose metabolism in hypertriglyceridemic
      patients with type 2 diabetes mellitus being a safe option to treat the diabetic
      population.

PMID- 25617538
TI  - [Effects of branched amino acids in endurance sports: a review].
AB  - INTRODUCTION: The report issued by the European Food Safety Agency (EFSA) in 2010
      on nutrition and health claims, shows that there is no scientific evidence to
      support supplementation with branched chain amino acids (BCAAs). The aim of this
      study is to analyze the effects of consumption of BCAAs in endurance sports.
      METHODS: A literature review on the current state of the effect of consumption of
      dietary supplements of BCAAs. We conducted a search in the PubMed database and
      snowball strategy. INCLUSION CRITERIA: Spanish / English randomized clinical
      trial related to the consumption of BCAAs, leucine, valine and isoleucine in
      endurance sports and its effects on muscle damage, athletic performance, central
      fatigue, anabolic signals during recovery and immune system response published in
      any country until May 2014. RESULTS: Out of 330 studies identified, 14 met the
      inclusion criteria. The mean of subjects participating in the study was (11.36+/
      7.43). Only two studies included a group of women. The sports that we found in
      the studies were: run, cycling, combining cycling and running, Olympic distance
      triathlon and one study included 2 groups of athletes (Olympic distance
      triathletes and runners). The effects of BCAAs and muscle damage, athletic
      performance, central fatigue, anabolic signals during recovery period and immune
      response were studied at different times: before, during and after training or a
      combination of these. DISCUSSION: It is observed that there is a lesser degree of
      pain and muscle damage, less perceived exertion and mental fatigue, greater
      anabolic response in recovery period and improved immune response when
      supplemented with BCAAs, notwithstanding its decision before or during physical
      activity does not improve athletic performance. No consensus was found in the
      dose and timing of the most effective decision, although it is more effective if
      there is 2-3/1/1g relationship between leucine / isoleucine and valine amino
      acids.

PMID- 25617539
TI  - [beta-hydroxy-beta-methylbutyrate as a dietary supplement (I): metabolism and
      toxicity].
AB  - INTRODUCTION: ?-hydroxy-?-methylbutyrate (HMB) is a leucine metabolite produced
      from ?-ketoisocaproic acid. HMB supplementation has been used as a dietary
      supplement in sports since 1997, with the aim of decreasing muscle proteolysis.
      In recent years, positive effects have been reported in different pathologies,
      which suggests potential health benefits. AIMS: The objectives of this review
      are: to know both HMB metabolism and toxicity, and to identify HMB cellular and
      molecular mechanisms of action when used as a dietary supplement. METHODS: A
      search was performed in the Web of Science, Pubmed and SportDiscus data bases.
      RESULTS were divided into two parts; this article presents the results about both
      HMB metabolism and possible toxicity. RESULTS: Studies show that HMB is related
      to cholesterol metabolism in skeletal muscle, which could reduce proteolysis,
      through hydroxy-methyl-glutaryl-coenzyme A and mevalonate as a precursor in the
      synthesis of cholesterol. However, HMB could also be transformed from
      acetoacetate to beta-hydroxybutyrate by beta-hydrozybutyrate dehydrogenase. The
      calcium salt of HMB is the most used chemical form in dietary supplements, being
      the most common dose 3 g of HMB/day. Studies in humans and animals provide
      evidence that there are no adverse effects associated with HMB supplementation.
      CONCLUSION: Metabolic effects and lack of toxicity of HMB make it an adequate
      compound to be used as a dietary supplement.

PMID- 25617540
TI  - [beta-hydroxy-beta-methylbutyrate as a dietary supplement (II): cell and
      molecular mechanism of action].
AB  - INTRODUCTION: In recent years, several investigations have related ?-hydroxy-?
      methylbutyrate (HMB) to a reduced muscle proteolysis and to an increase in muscle
      mass. Therefore, a number of studies focused on the cellular and molecular
      mechanisms regulating these effects have been carried out. AIMS: The objectives
      of this review are: to know both HMB metabolism and toxicity, and to identify HMB
      cellular and molecular mechanisms of action when used as a dietary supplement.
      METHODS: A search was performed in the Web of Science, Pubmed and SportDiscus
      data bases. RESULTS were divided into two parts; this article presents aspects
      referring to HMB mechanisms of action. RESULTS: There is insufficient evidence
      that HMB intake increases muscle cholesterol synthesis. It probably has positive
      effects on muscle metabolism through both the mTOR and ubiquitin-proteasome
      pathways, although the mechanism of action is unknown. HMB may increase blood
      levels of ?-hydroxybutyrate and this could explain the main effects of HMB on
      muscle proteolysis. CONCLUSION: According to these results, the possibility of
      justifying the action of HMB through the beta-hydroxybutyrate pathway opens an
      interesting line of research for future studies.

PMID- 25617541
TI  - [Breastfeeding for the prevention of overweight and obesity in children and
      teenagers; systematic review].
AB  - BACKGROUND: Breastfeeding is a recommended practice from national and
      international institutions due to the health benefits that it provides, both for
      the nursling and for the mother. Nowadays, overweight and obesity result in
      greater morbidity along different life periods. OBJECTIVE: The goal of this
      systematic review is to explore the characteristics of breastfeeding in the
      prevention of overweight and obesity during childhood. METHOD: A systematic
      search has been carried out and 113 papers have been selected: 20 meta-analysis
      and reviews, 6 original papers of clinical trials, 42 cohort or longitudinal
      studies, 19 correlational studies, 24 descriptive studies and 2 books. RESULTS:
      According to the analysed papers, there is a causal relationship between
      breastfeeding and the prevention of childhood obesity. DISCUSSION/CONCLUSION: In
      the various studies explored, it has been observed that the maximum benefits of
      breastfeeding are obtained when its duration is longer than 6 months and when it
      extends for two years, complemented with other foodstuffs. Other studies show
      that breastfeeding is effective in obesity prevention, even when its duration is
      limited. It is also important that complementary foods are introduced after the
      first six months of age, so as to reduce food allergy risk and to prevent
      obesity. Similarly, the weight of the mother during pregnancy has been associated
      with childhood obesity, as well as the weight of the child when he was born and
      other factors like maternal smoking and socioeconomic status.

PMID- 25617543
TI  - [Overweight and obesity in Colombian college students and its association with
      physical activity].
AB  - INTRODUCTION: Overweight, obesity and physical activity are considered modifiable
      factors related to development of chronic diseases. Taking into account physical
      activity patterns in college students, it is necessary to establish its
      association with the excessive weight in order to prevent and to decrease the
      prevalence of future chronic diseases. OBJECTIVE: The aim of this study was to
      determine the association between excessive weight and physical inactivity among
      college students. MATERIAL AND METHODS: An analytical cross sectional study was
      carried out in 2013 among college students from a private university of
      Bucaramanga, Colombia. Students (n=306) 18 to 25 years old were included using
      simple random sampling. An interview was realized using a survey that included
      the International Physical Activity Questionnaire (IPAQ), together with socio
      demographic variables. An assessment of body composition was realized in order to
      measure height, weight, body mass index (BMI), total fat percentage, and waist
      and hip circumferences. A trained professional in physical activity was in charge
      of data collection and anthropometric measurements. This study was approved by
      the university research and ethics committee. Participation was both voluntary
      and anonymous. All data were analyzed in compliance with the Helsinki
      Declaration. Written consent was signed by every participant of the study. A
      descriptive analysis of the studied population's general characteristics was
      realized. The association between excessive weight and physical inactivity was
      estimated using regression logistic models that allows estimate row and adjusted
      Odds Ratios (OR). RESULTS: An excessive weight was observed in 26.47% of the
      students, among which 20.26% were overweight and 6.21% obese, according to BMI
      cutoff. Taking into account the total fat percentage, 12.09% of the students were
      in risk of becoming obese and 10.13% were already obese. 50.56% of the students
      practiced very little weekly physical activity. The median of daily sedentary
      lifestyle was 12 hours, with an interquartile range of 4 hours. A statistically
      significant association was found between excessive weight and sedentary
      behavior, according to the total fat method (adjusted OR: 1.11, CI 95%: 1.01
      1.23). CONCLUSIONS: College students' health behavior is often inadequate in
      terms of physical activity and dietary habits. Our study observed an association
      between physical inactivity and excessive weight. Physical inactivity is an
      important lifestyle factor related to chronic diseases. Further research should
      focus on determinants to increase their physical activity and to improve their
      daily lifestyle in order to lower the risk of future diseases.

PMID- 25617542
TI  - Abdominal perimeter is associated with food intake, sociodemographic and
      behavioral factors among adults in southern Brazil: a population-based study.
AB  - OBJECTIVE: The aim of this study is to investigate the abdominal perimeter
      determinants in adults who live in the city of Lages, SC. DESIGN: A population
      based cross-sectional study in adults from 20 to 59 years-old of the urban area
      (n=2.022). The dependent variable is the abdominal perimeter, the independent
      variables are: age, skin color self-reported, marital status, number of children,
      per capita income, education, physical activity, smoking, nutrition, self
      reported diabetes mellitus, high blood pressure, body weight index. The
      differences between the mean perimeters were tested using ANOVA test and multiple
      linear regression for confounding adjustment. RESULTS: The response rate was
      98.2%, 52.3% were women. The mean abdominal perimeter for men was 93.66 cm (SD
      13.8) and for women 92.80 cm (SD 14.5). There was a positive association of
      abdominal circumference with age (p.

PMID- 25617544
TI  - Age group, menarche and regularity of menstrual cycles as efficiency predictors
      in the treatment of overweight.
AB  - OBJECTIVE: To evaluate if there is a relation between age groups, menarche,
      menstrual cycles and previous pregnancies with the success of weight loss in
      obese patients at a nutrition clinic. METHODS: A clinical intervention study was
      conducted among overweight and obese patients who consulted a nutrition clinic in
      Barranquilla (Colombia) for the purpose of nutritional assessment. They were
      subject to a personalized weekly follow-up consultation over the course of 16
      weeks in which food consumption patterns, anthropometric measures, body image and
      self-perception were registered. RESULTS: A total of 135 patients were evaluated.
      41 (30,4%) of whom did not complete the study. 69,6% patients did lose weight and
      83,7% did lose waist. These losses are lower in older ages (95,5% at.

PMID- 25617545
TI  - Resolution of type 2 diabetes and prediabetes following laparoscopic sleeve
      gastrectomy: medium term results.
AB  - PURPOSE: To determine the impact of Laparoscopic Sleeve Gastrectomy (LSG) on the
      resolution of type 2 diabetes (T2DM) and Prediabetes (PDM) in obese patients, as
      well as potential improvements in other comorbidities. MATERIAL AND METHODS:
      Observational retrospective study. We studied all patients with T2DM (n= 36) or
      PDM (n= 44) who underwent LSG in our hospital between years 2009 and 2012. PDM
      was defined as having at least 2 values of HbA1c between 5.7 and 6.4%. Follow-up
      period was 1-4 years (mean 17.5 months). T2DM remission criteria were fasting
      plasma glucose (FPG).

PMID- 25617546
TI  - [Validity and factorial invariance of the social ecological model in explaining
      fruit intake in Mexican schoolchildren].
AB  - OBJECTIVE: To test the goodness of fit of a Motivation-Ability-Opportunity model
      (MAO-model) to evaluate the observed variance in Mexican schoolchildren's
      preferences to eat fruit and daily fruit intake; also to evaluate the factorial
      invariance across the gender and type of population (urban and semi-urban) in
      which children reside. METHOD: A model with seven constructs was designed from a
      validated questionnaire to assess preferences, cognitive abilities, attitude,
      modelling, perceived barriers, accessibility at school, accessibility at home,
      and fruit intake frequency. The instrument was administered in a representative
      sample of 1434 schoolchildren of 5th and 6th grade of primary school in a cross
      sectional and ex post fact study conducted in 2013 in six cities of the State of
      Chihuahua, Mexico. RESULTS: The goodness of fit indexes was adequate for the MAO
      model and explained 39% of the variance in preference to eat fruit. The structure
      of the model showed very good factor structure stability and the dimensions of
      the scale were equivalent in the different samples analyzed. CONCLUSIONS: The
      model analyzed with structural equation modeling showed a parsimonious model that
      can be used to explain the variation in fruit intake of 10 to 12 year old Mexican
      schoolchildren. The structure of the model was strictly invariant in the
      different samples analyzed and showed evidence of cross validation. Finally,
      implications about the modification model to fit data from scholar settings and
      guidelines for future research are discussed.

PMID- 25617547
TI  - Anthropometric obesity indices in relation to age, educational level, occupation
      and physical activity in Bulgarian men.
AB  - OBJECTIVE: The objective of this study was to estimate the level of obesity and
      its relationship to age, educational level, occupation and physical activity in
      adult Bulgarian men. MATERIAL AND METHODS: The sample included 1010 men, aged 18
      50 years old, from town of Plovdiv, Bulgaria. The study was made in period 2004
      2008. The body height, weight and waist circumference were measured. Overweight
      and obesity were defined according to the international cut-off points of body
      mass index (BMI). The abdominal obesity was assess by the categories of waist
      height ratio (WHTR).The age, educational level, occupation and physical activity
      of each person were investigated through inquiry. For statistical analysis the
      SPSS package was used. RESULTS: The results shown that 42.1% of investigated men
      were overweight and 19.4% of them were with obesity.With irregular WHTR and
      central obesity were 66.1% of all cases. The percent of men with general and
      central obesity increases with age. In the case of both general and central
      obesity, the differences between physical and intellectual workers are
      significance, even after controlling the age.WHTR has a greater potential for
      differentiating persons with different occupations than BMI. The age and
      occupation were the most significant factors affecting the general and abdominal
      obesity. The educational level has a significant impact on abdominal accumulation
      of fat.The connection between level of physical activity and BMI and WHTR was
      lower. CONCLUSION: The study finds that the men working and living in that
      particular urban area have significant differences in terms of overweight and
      obesity. The educational level, occupation and age have a serious potential to
      influenced their body nutritional status.

PMID- 25617548
TI  - Ferritin in hypertensive and diabetic women before and after bariatric surgery.
AB  - In addition to its important role as marker of iron stores, serum ferritin is a
      marker of systemic inflammation, and obesity has been associated with chronic
      inflammation. OBJECTIVE: To verify, six months after surgery, the effect of
      bariatric surgery on the serum ferritin of women who were hypertensive, diabetic,
      or comorbidity free before surgery. SAMPLE AND METHODS: This retrospective study
      included 200 women aged 20 to 45 years, with a body mass index (BMI) equal to or
      greater than 35 kg/m2, submitted to Roux-en-Y gastric bypass (RYGB). Seventy of
      these women were hypertensive, forty had type 2 diabetes (T2D), and ninety were
      comorbidity free (CF). They were assessed before and six months after surgery.
      Anthropometric, laboratory (serum ferritin and hemoglobin), and comorbidity-
      related data were collected from their medical records. RESULTS: Before surgery,
      women with comorbidities were older, the hypertensives had higher BMI, and the
      diabetics had higher serum ferritin levels than the CF women. The study
      comorbidities had resolved in 68% of the hypertensive women and 86% of the
      diabetic women six months after RYGB. Also at this time, the serum ferritin of
      hypertensive women decreased from 110.1+/-86.3 to 88.7+/-80.5 ng/dL and of
      diabetic women, from 164.8+/-133.4 to 101.2+/-97.7 ng/dL (p0.05). CONCLUSION:
      High ferritin in premenopausal obese women was associated with the main obesity
      related comorbidities, and these comorbidities determined the reduction of serum
      ferritin after bariatric surgery.

PMID- 25617549
TI  - [Eating habits of patients with severe obesity].
AB  - INTRODUCTION: Severe obesity is a health problem that has medical, emotional and
      economic consequences. The etiology of severe obesity is multifactorial; however,
      it is known that the eating habits represent a major factor in the development of
      this disease. OBJECTIVE: This study aimed to identify eating patterns and
      specific habits that need to be changed to achieve weight loss. METHOD: An
      observational, descriptive, retrospective and cross-sectional study with 250
      candidates for bariatric surgery, 79.2% women and 20.8% men aged 37.7 +/- 10.2
      years and 44.3 +/- 7.7 kg/m2 BMI patients was performed. RESULTS: It was found
      that "drinking water", "eat faster than most people", "leave the plate empty",
      "have long fasts", "sweet cravings", and "drinking soda" were the most common
      habits in patients with severe obesity. The existence of significant differences
      between the habits of men and women and between BMI strata or groups are also
      discussed. "Snacking" and "eat until you feel uncomfortable" were significantly
      different between men and women and "eat by yourself because you feel ashamed of
      eating with others" was significant between BMI strata. DISCUSSION: It was
      concluded that it is important that the treatment of these patients includes
      assessment techniques and behavior modification aimed at these habits. It is
      recommended to include in future studies patients with normal weight and
      overweight as well as the use of instruments with adequate psychometric
      properties.

PMID- 25617550
TI  - [Weight-for-age percentile curves for the population of Catamarca province
      (Argentina)].
AB  - INTRODUCTION: The assessment of fetal development and birth weight is a priority
      in the field of nutritional epidemiology and public health. Nowadays, the World
      Health Organization (WHO) does not have specific birth weight curves for the
      distinct gestational weeks considering that socio-economic, ecological and ethnic
      characteristics of the different human groups are found influencing their own
      growth patterns. OBJECTIVE: This research develops centile curves for weight by
      gestational age concerning to resident populations in the province of Catamarca.
      METHODS: In order to process data, SPSS statistical program was used, as well as
      LMS Chart Maker pro program for the subsequent performing of centile curves. The
      sample ascended to a total of 22,576 childbirths between 1994 and 2003.
      DISCUSSION AND CONCLUSION: In the future, these curves make possible a better
      assessment of intrauterine development and birth weight in this region of
      Northwest of Argentina.

PMID- 25617551
TI  - Effectiveness of the Brazilian Conditional Cash Transfer Program--Bolsa
      Alimentacao--on the variation of linear and ponderal increment in children from
      northeast of Brazil.
AB  - BACKGROUND: Social programs can improve the conditions required for families
      provide sufficient care and attention for an adequate health and nutrition.
      OBJECTIVE: This study evaluates the effectiveness of the Brazilian's conditional
      cash transfer program - Bolsa Alimentacao (PBA) on children anthropometric
      status. METHODS: A cohort of 1847 children, followed for 12 months: 1615 PBA
      children; 232 non-PBA. There were 316 (14.6%) missing children during the study.
      A quasi- experimental study adopting the before-after strategy was applied and
      the effectiveness approach was used to assess the impact of the program on
      children nutritional status. Multilevel analysis with three levels was used in
      the statistical analysis. The mean increment variations of height-for-age and
      weight-for-age were the outcome variables and the participation in the PBA was
      the exposition. Four participation groups were established: children not exposed
      to the program (internal control group); exposed to the program throughout the 12
      months, exposed to the program only in the last 6 months; and exposed to the
      program only in the first 6 months. Repeated measures were obtained at baseline
      and at 12 months. RESULTS: It was found that the exposure to the program was
      associated to a mean variation in weight-for-age of 0.34 Z-score (IC=-0.44; 0.63)
      and height-for-age of 0.38 (IC=0.05; 0.70) for children who were regular program
      beneficiaries during the follow-up. The exposure to the program in other periods
      was not statistically associated with a mean variation in the indicators.
      CONCLUSIONS: Cash transfers direct to the family were associated to
      anthropometric deficits reduction in childhood.

PMID- 25617552
TI  - Body image and weight status of children from rural areas of Valparaiso, Chile.
AB  - OBJECTIVE: To determine the relation between the perceived and the real
      nutritional status in children from rural areas. PARTICIPANTS: The study
      comprehends 206 students from first to eighth year of primary school from rural
      institutions of the Valparaiso region, Chile (43% females). METHODS: The real
      nutritional status was measured using the Body Mass Index (BMI), and the
      perceived status by means of corporeal figures. The Socioeconomic Status (SES)
      was determined using the modified Graffar scale. The analysis was carried out
      using the concordance correlation coefficient kappa, and the chi-square test was
      used for the association of variables. RESULTS: The subjects are concentrated in
      the low SES (82% male; 72% female). 49.5% of the students present overweight and
      obesity. Boys show higher prevalence of obesity (29%) than girls (20%). 62.5% of
      the females underestimate their weight, which surpasses the percentage of males
      (52.5%). 98.10% of the obese individuals underestimate their weight, as well as
      the 100% of the evaluated children with an overweight condition. CONCLUSIONS:
      Boys and girls from rural areas in conditions of overweight and obesity present a
      higher prevalence rate of an inappropriate perception of body image
      (underestimation), which has an important impact when recognizing their own
      condition of over nutrition. This status can have significant repercussions in
      public health, since it can be maintained to adult life and develop non
      transmissible chronic diseases.

PMID- 25617553
TI  - [Reference values for cholesterol, triglycerides and glucose in a population of
      Hispanic children from 6 to 11 y, in the northern border of Mexico and the United
      States of America].
AB  - INTRODUCTION: Overweight and obesity in children in the Mexico-USA border have
      evolved differently to the rest of their respective countries. New reference
      values of cholesterol, triglycerides and glucose are required to treatment.
      OBJECTIVE: To determine the reference values of cholesterol, triglycerides and
      glucose in Hispanic children between 6 and 11 years in the Mexico-USA border.
      METHODS: A prospective, cross-sectional, descriptive and observational study. A
      population of Hispanic children between 6 and 11 years of both boys and girls,
      belonging to three public institutions in the cities of Ensenada and Chihuahua,
      randomly selected, were studied. The study variables were the levels of total
      cholesterol (TC), triglycerides (TG) and glucose (G). RESULTS: From 300 subjects
      studied just 54 children completed the study. Higher average values of TC (168.7
      +/- 27.2 mg / dl), TG (80.6 +/- 48.4 mg / dl) and G (88.3 +/- 8.9 mg / dl) were
      observed. An additional behavior was founded, never reported previously to the
      limit of the knowledge of the authors; glucose levels of the children studied
      decreased with increased of cholesterol and triglycerides. To discard a random
      relationship between the variables, the Pearson correlation coefficient was
      determined between waist circumference and BMI, verifying an inverse association
      with G and direct with the TG. CONCLUSION: The reference values for Hispanic
      children between 6 and 11 years living on the northern border of Mexico-USA
      differ with respect to the national average values of the countries studied.
      Further studies are needed in larger populations to confirm the trend ob served
      in glucose levels of normal children, overweight and obese.

PMID- 25617554
TI  - Association between TGFBR2 gene polymorphisms and congenital heart defects in Han
      Chinese population.
AB  - BACKGROUND: Transforming growth factor-beta receptor II (TGFBR2) is a key
      component of TGF-beta signaling pathway. TGFBR2 can be detected in the generation
      of heart. The mouse embryos of TGFBR2 gene knockout exhibited congenital heart
      defects. METHODS: We conducted a case-control study to investigate the
      association between TGFBR2 gene polymorphisms and congenital heart defects in Han
      Chinese population. 125 patients with congenital heart defects and 615 unrelated
      controls were recruited. Two tagging single nucleotide polymorphisms (tagSNPs) in
      5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/ G) were
      selected and genotyped by polymerase chain reaction (PCR)-restriction fragment
      length polymorphism (RFLP) assay. RESULTS: A significant difference was seen in
      the distribution of genotypes between patients with congenital heart defects and
      controls for SNP rs6785358 (P=0.043). For SNP rs6785358 the carrier of the G
      allele (AG/GG genotype) showed a significantly higher risk of congenital heart
      defects compared with AA homozygotes (OR=1.545, 95% CI: 1.013-2.356). Further
      analysis by sex stratification indicated that individuals carrying G allele
      (AG/GG genotype) for SNP rs6785358 have a higher susceptibility to congenital
      heart defects (OR=2.088, 95%CI: 1.123-3.883, P=0.019) in males, but not females
      (OR=1.195, 95%CI: 0.666-2.146, P=0.55). No statistical significance was detected
      in the distribution of genotypes and allele frequencies for SNP rs764522 between
      patients and controls. CONCLUSION: Our result suggested that SNP rs6785358 of
      TGFBR2 gene was associated with increased risk of congenital heart defects in Han
      Chinese men and further research would be warranted.

PMID- 25617555
TI  - [Effect of nutrition on growth and neurodevelopment in the preterm infant: a
      systematic review].
AB  - INTRODUCTION: The energy needs of preterm infants are high and more so when the
      body weight is lower; for this reason, and to safeguard the infant's future
      development, it is important to ensure an optimal caloric intake is obtained.
      AIM: To analyse leading research papers related to nutrition in the preterm
      newborn and its effects on growth and development. METHOD: Systematic review of
      relevant studies, based on the application of a search strategy, from March to
      September 2014. The literature search was conducted using document analysis and
      information synthesis to classify and compile the information extracted, followed
      by a comparative evaluation. The validity of the articles obtained was
      corroborated by the weight of findings obtained, by the citations received by the
      articles and by their applicability to our healthcare environment. RESULTS: The
      search process produced 61 studies that met the selection criteria. The research
      question addressed has been widely examined and many studies have reported
      findings related to the nutrition of preterm infants. The direct relationship
      between nutritional intake and the growth rate of preterm infants is well
      documented. CONCLUSIONS: Proper nutrition in the preterm infant has positive
      effects on its growth and neurodevelopment. It has been reported that a greater
      intake of proteins and lipids favours the growth of preterm infants, but not
      weight gain. Studies have demonstrated the beneficial effect of breast milk on
      the brain, the retina and the blood vessels; however, there is a negative
      correlation between adiposity and brain volume.

PMID- 25617556
TI  - [Relationship between body weight status and self-concept in schoolchildren].
AB  - Body weight status has been linked to other health parameters. The aim of this
      study was to evaluate the relationship between body weight status and self
      concept in a sample of 216 students (9.26 +/- 1.26 years) from schools of the
      Southeast of Spain. BMI (Body-mass index) was used to evaluate the body weight
      status. Subjects were classified into normal weight, overweight and obesity
      according to international standards. The six dimensions of self-concept
      (intellectual, behavioral, physical, lack of anxiety, social and life
      satisfaction) were assessed using the Piers-Harris Self-Concept Scale. The
      results showed significant associations between BMI and intellectual self
      concept, life satisfaction, global self-concept and physical self. Subjects
      categorized as overweight or obese were those who showed lower scores on the self
      concept scale. Interventions focused on improving the body weight status are
      needed in order to achieve better self-concept levels and health among young
      people. 

PMID- 25617557
TI  - [Nutritional status and health-related life quality in school children from the
      southeast of Spain].
AB  - INTRODUCTION AND OBJECTIVE: Analyze the level of Life Quality (LQ) in relation to
      nutritional status in a sample of primary school children. MATERIAL AND METHODS:
      Cross sectional study with 298 participants (53.35% female) of 8-12 years. LQ was
      assessed by the KIDSCREEN-10 questionnaire . Measures of weight and size were
      taken. The BMI (normal-weight, overweight and obesity) was categorized using
      standard criteria. To establish the relationship between the different
      statistical variables was performed the Kolmogorov- Smirnov test and analysis of
      variance. RESULTS: Nutritional status was significantly correlated with LQ (F =
      5.096; p =, 007). School children with a normal- weight state showed higher LQ
      levels compared to those overweight (p = .015) and obese (p =, 013). CONCLUSIONS:
      The results show that nutritional status acts as a differentiating factor in LQ.
      Adopting active lifestyle behaviours that promote a healthy nutritional status
      not only can have benefits over health biological parameters (such as physical
      condition) but can also contribute to improve other LQ indicators and mental
      health .

PMID- 25617558
TI  - [SNP-19 genotypic variants of CAPN10 gene and its relation to diabetes mellitus
      type 2 in a population of Ciudad Juarez, Mexico].
AB  - INTRODUCTION: Diabetes Mellitus (DM) type 2 is a common pathology with
      multifactorial etiology, which exact genetic bases remain unknown. Some studies
      suggest that single nucleotides polymorphisms (SNPs) in the CAPN10 gene (Locus
      2q37.3) could be associated with the development of this disease, including the
      insertion/deletion polymorphism SNP-19 (2R->3R). OBJECTIVE: The present study
      determined the association between the SNP-19 and the risk of developing DM type
      2 in Ciudad Juarez population. METHODOLOGY: For this study 107 participants were
      selected: 43 diabetics type 2 (cases) and 64 non diabetics with no family history
      of DM type 2 in first grade (control). Anthropometric studies were realized as
      well as lipids, lipoproteins and serum glucose biochemical profiles. The
      genotypification of SNP-19 was performed using peripheral blood lymphocytes DNA,
      polymerase chain reactions (PCR), and electrophoretic analysis in agarose gels.
      Once obtained the genotypic and allelic frequencies, the Hardy-Weinberg
      equilibrium test (GenAlEx 6.4) was also performed. RESULTS: Using the X2 analysis
      it was identified the genotypic differences between cases and control with higher
      frequency of the homozygous genotype 3R of SNP- 19 in the cases group (0.418)
      compared to control group (0.265). Also, it was observed an association between
      genotype 2R/3R with elevated weight, body mass index, and waist and hip
      circumferences, but only in the diabetic group (P=< 0.05). CONCLUSION: The
      findings in this study suggest that SNP-19 in CAPN10 may participate in the
      development of DM type 2 in the studied population.

PMID- 25617559
TI  - Nutritional and metabolic status of breast cancer women.
AB  - INTRODUCTION: The nutritional and metabolic status have been related to cancer
      risk factors as well as to cancer treatment morbimortality. Thus, its assessment
      is important for developing strategies for the promotion, maintenance and / or
      recovery of nutritional status and cancer outcome. MATERIAL AND METHODS: Several
      different methods for nutritional assessment in breast cancer patients undergoing
      adjuvant therapy were used, including subjective global assessment (SGA), body
      mass index (BMI), triceps skinfold (TSF), mid-arm circumference (MAC), adductor
      pollicis muscle thickness (APMT), hand grip strength (HGS) and bioelectrical
      impedance analysis (BIA). The presence of metabolic syndrome (MetS) was also
      evaluated. The occurrence of complications during cancer treatment versus the
      nutritional status was assessed. RESULTS: We followed 78 women with a mean age of
      53.2 ?} 11.6 years. Most patients were considered well nourished (80.8%).
      Excessive body fat mass by BIA and MetS were found in 80,8 % and 41.9% of the
      patients respectively. There were significant differences in BMI, TSF, WC (waist
      circumference) and % fat mass between patients with and without MetS. Most
      patients experienced complications during cancer treatment, but there was no
      association with nutritional or metabolic status. CONCLUSION: In breast cancer
      women undergoing adjuvant therapy, the prevalence of metabolic syndrome was high
      and, on the contrary, undernutrition was low. There were no short-term effects of
      metabolic syndrome or undernutrition on clinical outcomes.

PMID- 25617560
TI  - Clinical effects of a hypercaloric and hyperproteic oral suplemment enhanced with
      W3 fatty acids and dietary fiber in postsurgical ambulatory head and neck cancer
      patients.
AB  - BACKGROUND: Patients with head and neck cancer undergoing surgery have a high
      risk of nutritional complications. OBJECTIVE: The aim of our study was to
      investigate the influence of a hypercaloric and hyperproteic oral supplement
      enriched with w3 FATTY ACIDS and fiber in clinical parameters in head and neck
      tumor postsurgical ambulatory patients with or without radiotherapy. DESIGN: A
      population of 37 ambulatory postsurgical patients with oral and laryngeal cancer
      was enrolled. At Hospital discharge postsurgical head and neck cancer patients
      were asked to consume two units per day of a hypercaloric and hyperproteic oral
      supplement for a twelve week period. RESULTS: The mean age was 63.8+/-7.1 years
      (16 female/ 21 males). Duration of supplementation was 98.1+/-19.1 days. A
      significant increase of albumin and transferrin levels was observed, in total
      group and in patients undergoing radiotherapy and without it. No differences were
      detected in weight and other anthropometric parameters in total group and in
      patients with radiotherapy during the protocol. Nevertheless, patients without
      radiotherapy showed a significant improvement of BMI; weight, fat free mass and
      fat mass. CONCLUSIONS: An omega 3 and fiber enriched formula improved seric
      protein levels in ambulatory postoperative head and neck cancer patients.
      Improvement of weight, fat mass and fat free mass was observed in patients whom
      not received radiotherapy during the follow up.

PMID- 25617561
TI  - Effects of dietary supplementation with lemon verbena extracts on serum
      inflammatory markers of multiple sclerosis patients.
AB  - INTRODUCTION: Inflammation is one of the main contributory factors to the
      etiopathogenesis of multiple sclerosis (MS). Dietary interventions with Lipia
      citriadora (lemon verbena) extracts have been proved to be effective in the
      prevention of inflammatory diseases. OBJECTIVES: The aim of this study is to
      evaluate the effect of lemon verbena supplementation in pro- and anti-
      inflammatory serum biomarkers of patients with different clinical subtypes of
      multiple sclerosis. METHODS: The effect of lemon verbena supplementation (10% w/w
      verbascoside) was evaluated in a randomized, double-blinded placebo-controlled
      study with 30 participants classified in relapsing-remitting (n=10), primary
      progressive (n=5) and secondary progressive (n=15) MS presentations. Serum
      cytokine and C reactive protein levels were assessed in intervention and control
      groups for each MS clinical subtype after 28 days of dietary supplementation.
      RESULTS: Serum levels of C reactive protein and 8 cytokines/ inflammatory (IFN
      gamma, IL-12, IL-23, IL-6, TNF-alpha, TGF-beta, IL-4 and IL-10) markers were
      studied. Secondary progressive MS- supplemented patients showed C reactive
      protein concentrations significantly lower compared to the placebo group (p.

PMID- 25617562
TI  - Fructose intake: is there an association with uric acid levels in nondialysis
      dependent chronic kidney disease patients?
AB  - INTRODUCTION: Fructose intake has increased dramatically in consequence of the
      consumption of fructose-based sweetened foods and beverages. Research suggests
      that high fructose intake has a strong association with uric acid (UA) levels and
      worse prognosis of chronic kidney disease (CKD). OBJECTIVE: The aim of this study
      was to investigate the influence of fructose intake on plasma UA levels in
      nondialysis- dependent CKD patients. METHODS: Fifty-two patients on stages 3-5
      (64.2 +/- 9.6 years, 24 men, glomerular filtration rate of 30.5 +/- 10.3 ml/ min)
      were divided into two groups: high fructose intake (>50 g/d, n=29, 61.7 +/- 9.3
      years) and low fructose intake (

PMID- 25617563
TI  - The effect of Saccharomyces boulardii in patients eligible for liver
      transplantation.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of Saccharomyces
      boulardii on the intestinal permeability, laboratory parameters and MELD and
      Child-Pugh severity scores in cirrhotic patients eligible for liver
      transplantation. METHODS: Eighteen patients followed in a Transplant Outpatient
      Clinic were evaluated immediately before the beginning of treatment, after a 30
      day period of treatment period with probiotics and at the end of the second study
      month (after a thirty-day period without probiotics). Fifteen healthy controls
      also underwent the intestinal permeability test (lactulose/mannitol). RESULTS:
      Before the probiotic, the median lactulose/ mannitol ratio was greater in the
      cirrhotic patients (0.0209, range 0.0012-0.1984) compared to the healthy controls
      (0.0030, range 0.0020-0.0013) (p < 0.05). Eight of fifteen patients, half of whom
      had ascites, showed increased intestinal permeability above the higher value
      observed in the controls. No significant association was found between the
      severity scores for liver disease, age, presence of ascites and intestinal
      permeability immediately before the beginning of study. After treatment with S.
      boulardii, there was no improvement in intestinal permeability or significant
      differences in the laboratory parameters for the three evaluations. CONCLUSIONS:
      Patients eligible for liver transplants presented with increased intestinal
      permeability compared to healthy controls. A thirty-day treatment with S.
      boulardii did not improve this intestinal permeability or the severity scores,
      nor did it impact the laboratory parameters.

PMID- 25617564
TI  - [A lower adherence to Mediterranean diet is associated with a poorer self-rated
      health in university population].
AB  - INTRODUCTION AND OBJECTIVE: A higher adherence to Mediterranean diet is
      considered as a protective factor against the large number of deaths attributable
      to the main chronic degenerative diseases in developed countries. Self-rated
      health is established as a good indicator of population health status and as a
      predictor of mortality. Studies exploring the relationship between the adherence
      to Mediterranean diet and self-rated health are scarce, especially, in young
      adults. Our aim was to explore the factors related, specially the adherence to a
      priori-defined Mediterranean diet with self-rated health in a cohort of Spanish
      university students. METHODS: We analyzed data from 1110 participants of Spanish
      DiSA-UMH (Dieta, Salud y Antropometria en universitarios de la Universidad Miguel
      Hernandez) study. Diet was assessed using a validated food frequency
      questionnaire and the adherence to Mediterranean diet was calculated using the
      relative Mediterranean Diet Score (rMED; score range: 0-18) according to the
      consumption of 9 dietary components. Self-rated health was gathered from the
      question: "In general, how do you consider your health to be? (Excellent, good,
      fair, poor, very poor). Information on sociodemographic and lifestyle
      characteristics was also collected. Multinomial logistic regression (using
      relative risk ratio, RRR) was used to analyze the association between the
      adherence to Mediterranean diet (low rMED: 0-6 points; medium: 7-10 points; high:
      11-18 points) and self-rated health (Excellent (reference), good and fair/
      poor/very poor). RESULTS: A low, medium or high adherence to Mediterranean diet
      conformed to 26.8%, 58.7% and 14.4% of participants, which of them reported an
      excellent (23.1%), good (65.1%) and fair/poor or very poor health, respectively.
      In multivariate analysis, a lower adherence to Mediterranean diet was
      significantly (p.

PMID- 25617565
TI  - Ferritin levels in pregnant Colombian women.
AB  - OBJECTIVE: Ferritin deficiency is associated with many adverse health outcomes
      and is highly prevalent worldwide. The present study assesses the prevalence and
      socio-demographic factors associated with ferritin deficiency in a representative
      sample of pregnant women in Colombia. METHODS: We used data from the cross
      sectional, nationally representative survey National Nutritional Survey (ENSIN,
      2010). A total of 1,386, (13-49 years old) pregnant women were enrolled. Serum
      ferritin a concentration was determined by chemiluminescence and sociodemographic
      date (age, urbanicity geographic region, ethnicity and socioeconomic level
      SISBEN), was assessed by computer-assisted personal interview technology.
      Multivariate analyses using unordered binomial logistic regression models were
      conducted in the main analysis. RESULTS: The overall prevalence of ferritin
      deficiency (serum.

PMID- 25617566
TI  - The density and species of mite breeding in stored products in China.
AB  - OBJECTIVE: The aim of our study was to investigate the species and breeding
      density of acaroid mites in stored products in China. METHODS: We tentatively
      harvested the samples from the products stored in warehouses, commercial stores
      and civilian houses, and the products. RESULTS: The results suggested the mites
      varied a lot in species regarding their ecological habitus and habitat. Still,
      the breeding density in different samples was associated with the sampling
      conditions. CONCLUSIONS: These discrepancies may be associated with the samples
      collected in diverse environment for the mites, and the findings easily suggest
      that acaroid mites are in universal distribution.

PMID- 25617567
TI  - Gohieria fusca (Acari: Astigmata) found in the filter dusts of air conditioners
      in China.
AB  - OBJECTIVE: Gohieria fusca(Oudemans, 1902) is recognized to breed in wheat flour,
      rice, corn, feeds, wheat bran and herbal medicines as well as other stored
      products, and capable of having mild to moderate cross reactivity with allergens
      of house dust mites, an important source of indoor allergens associated with
      asthma and other allergic conditions. Air-conditioning systems are indispensable
      in public and civil buildings, and the screens of the air conditioners are the
      most places to accumulate dusts. In order to investigate whether Gohieria fusca
      can breed in the screens of air-conditioners equipped at either public spaces or
      civil dwellings in Wuhu city, Anhui province, China. METHODS: We collected 430
      dust samples from the filters of air-conditioning systems at the school
      cafeteria, marketplaces, hotels and civil buildings between June and September of
      2013, and isolated Gohieria fusca from the previous samples. RESULTS: The results
      suggested that Gohieria fusca was present in 98 of the 430 samples (22.79%), and
      the breeding rate was significant in the air-conditioning filters from different
      spaces (c2=18.294, P.

PMID- 25617568
TI  - Preliminary report on the intestinal parasites and their diversity in captive
      Chinese alligators.
AB  - OBJECTIVE: Although intestinal parasites are commonly detected in either wild or
      farmed crocodiles in other parts of the world, yet few reports have ever been on
      the captive bred Chinese alligators (Alligator sinensis) since they are only
      distributed in the southern areas of the Yangtze River. The current work was
      undertaken to investigate the intestinal parasites and their diversity in the
      Chinese crocodilian species. METHODS: In May and October of 2013, we randomly
      collected a total of 328 fecal samples of the captive Chinese alligators in a
      breeding centre in south Anhui province. RESULTS: Three genera of protozoa
      (Entaoeba, Eimeria and Isospora), five genera of nematodes (Ascaris,
      Dujardinascaris, Capillaria, Toxocara and Strongylus), two genera of trematodes
      (Echinostoma and Clonorchis) and two families of trematodes (Schistosomatidae and
      Cryptogonimidae) were identified, in which Dujardinascaris was the most prevalent
      and led to the highest infection rate (14.33%), and Entaoeba ranked the second
      (13.11%). The number of species, richness index, diversity index and evenness
      index were higher in July and August, and those indexes were relatively most in
      juvenile and subadult alligators. CONCLUSIONS: Our findings suggest that the
      intestinal parasites infection was prevalent in captive Chinese alligators, and
      this condition requires our attention, whatever it is for controlling or
      preventing the intestinal parasitic disease from spreading to humans or
      conservation of this endangered species.

PMID- 25617569
TI  - [Factors associated with mortality in patients with dysphagia help in making
      dietary and nutritional choices].
AB  - OBJECTIVE: To know what factors evaluated at the moment of admission are related
      with mortality among in-patients with dysphagia, during their stay in a longterm
      care hospital and may guide the dietary and nutritional intervention. MATERIAL
      AND METHODS: Retrospective, observational and descriptive cohort study over
      patients with dysphagia diagnosed by Volumen-Viscosity Clinical Exploration
      Method (VVCEM). Demographic and clinical variables were gathered, stay,
      mortality, when their dysphagia was re-evaluated and treatments. RESULTS: 182
      patients were included, medium age of 78 years old, 50% of them died. Following
      factors were significantly associate with death by univariant analysis: aged 85
      or older, previous diagnosis of dysphagia, oncological disease, high co-morbidity
      (Charlson between 2-5 and > 5 points), low functionality before hospitalization
      (Barthel Index < 40), MNA < 17 points, albumen < 3 g/ dl, high score in CONUT (5
      12 points), to be on opioids, neuroleptics, antidepressants while performing
      VVCEM, and the assistance aim when admission. Following factors had signification
      for risk to die by multi-variant analysis: age, oncological disease, co-morbidity
      and albumen, but taking antidepressants turned out to be a protective factor.
      Analysis of contrast was applied by curve ROC. The area under the curve was 0.740
      and the confidence interval (CI) 0.668-0.811. CONCLUSIONS: The above-mentioned
      information that may be evaluated in patients with dysphagia when admission, may
      help to define of more suitable and precocious form our welfare aims. In those
      cases with major risk of dying, it should prioritize comfort and safe swallowing.
      In those cases with low risk, in addition, should be effective improve to the
      maximum their nutritional condition.

PMID- 25617570
TI  - Stature estimation using the knee height measurement amongst Brazilian elderly.
AB  - INTRODUCTION: Stature is an important variable in several indices of nutritional
      status that are applicable to elderly persons. However, stature is difficult or
      impossible to measure in elderly because they are often unable to maintain the
      standing position. A alternative is the use of estimated height from measurements
      of knee height measure. AIMS: This study aimed to evaluate the accuracy of the
      formula proposed by Chumlea et al. (1985) based on the knee of a Caucasian
      population to estimate the height and its application in calculation of body mass
      index in community- dwelling older people residents in Vicosa, Minas Gerais,
      Brazil. METHODS: The sample included 621 elderly aged 60 years old and older,
      living in the community. Measures of weight, height and knee height (KH) were
      taken and Body Mass Index (BMI) was calculated with the measured weight and
      estimated. The Student's t-test was used for comparison of measurements of height
      between the genders. For the comparison of estimated and measured values it was
      used paired t-test and also the methodology proposed by Bland and Altman to
      compare the difference between measurements. To evaluate the agreement between
      the classifications for BMI was used Cohen's Kappa. RESULTS: The average values
      obtained from KH were higher than those measured in the whole sample and women.
      There underestimation of BMI in females and also in the whole. CONCLUSIONS: The
      present results suggest that the equation Chumlea was not adequate to estimate
      the height of the sample in question, especially for women.

PMID- 25617572
TI  - Alternative options for prescribing physical activity among obese children and
      adolescents: brisk walking supported by an exergaming platform.
AB  - BACKGROUND: Physical inactivity has been identified as an important public health
      concern for children. An increasing sedentary way of life is directly related to
      obesity; hence, prevention and management of childhood obesity are commonly based
      on lifestyle interventions wherein increasing physical activity is one of the
      main targets. The use of exergames can be useful in promoting physical activity,
      but it is necessary more research. This study analyzes the effects of an
      exergaming platform that involves brisk walking, on perceived exertion, self
      efficacy, positive expectations and satisfaction in a sample of clinically obese
      children, as compared with normal weight children. Physiological variables like
      heart rate, oxygen consumption and energy expenditure were also measured. METHOD:
      A total sample of 42 children was recruited. Children were randomized into those
      walking on a treadmill and those using a treadmill with the support of the
      exergaming platform (Wii-Fit). RESULTS: The obese children scored significantly
      higher in expectations and satisfaction in the exergame condition but not in self
      efficacy, perceived exertion or physiological measures. CONCLUSIONS: These
      results suggest that this exergaming platform could be a tool to assist obese
      children in the practice of brisk walking as part of a programme designed to
      treat obesity.

PMID- 25617571
TI  - [Determination of 2-hydroxyestrone /16alpha-hydroxyestrone ratio in urine of
      Mexican women as a risk indicator for breast cancer and its relationship with
      other risk factors].
AB  - The urinary ratio 2-hydroxyoestrone/16?-hydroxyoestrone (URME), has been proposed
      in various populations on the world as a risk indicator for breast cancer (BC),
      however in the Mexican population has never been determined. OBJECTIVE: To
      determine URME Mexican women and establish its relationship with risk factors for
      BC. MATERIAL AND METHODS: Cross-sectional study of 142 premenopausal and 42
      posmenopausal women. The URME was determined with the kit ESTRAMETTM and was
      related to risk factors for BC. Correlations and linear regressions were
      performed. RESULTS: The median URME was 0.90 (RIQ 0.64-1.18). The body mass index
      (BMI) and early menarche contribute 5.4% of their variability (F=5.17; p.

PMID- 25617573
TI  - Influence of anthropometric profile on physical performance in elite female
      volleyballers in relation to playing position.
AB  - INTRODUCTION: The anthropometric profile, specifically body composition, plays a
      crucial role in the physical performance of volleyballers. Since there are
      varying positions in volleyball, it is likely that differences exist in
      anthropometric and physical performance profiles among players due each role's
      specific physical requirements. OBJECTIVES: The aims of this study were to
      analyze the anthropometric and physical performance profiles of elite female
      volleyballers, to determine any differences in these features among different
      playing positions. A further aim was to examine any relationship between
      anthropometric measures and measures of performance. METHODS: This study assessed
      42 female professional volleyball players (Age: 27.2+/-5.4 years). Players were
      categorized according to playing position: middle blockers (n=12), opposite
      hitters (n=6), outside hitters (n=12), setters (n=8), and liberos (n=4).
      Anthropometric measurements assessed were: height, weight, fat mass (5 skinfolds)
      musculoskeletal mass (5 corrected girths). Additionally, the physical performance
      parameters examined were: jump tests (vertical-jump and spike-jump), speed,
      agility, and strength tests (crunches test and overhead medicine ball throw).
      RESULTS: In terms of height middle blockers were the tallest (186.5+/-1.4 cm),
      while liberos were the shortest (166.7+/-8.1 cm). There were significant
      differences in body mass among positions (p.

PMID- 25617574
TI  - The prevalence of barriers for Colombian college students engaging in physical
      activity.
AB  - OBJECTIVE: To investigate the prevalence of barriers and their association with
      Colombia college students engaging in PA. METHODS: A total of 5,663 students
      (3,348 male) from three cities in Colombia. In fall 2013, students voluntarily
      completed a demographic questionnaire, Barriers to Being Active Quiz. Logistic
      regression analysis of each barrier (adjusted for confusion variables: gender,
      age and BMI) was used for verifying such association. RESULTS: The most prevalent
      barriers in overweight individuals were "fear of injury" (87.0%), "lack of skill"
      (79.8%) and "lack of resources" (64.3%). The group of females revealed a
      protective association regarding "lack of time" (OR=0.53: 0.47-0.60 95%CI),
      "social influence" (OR=0.67: 0.60-0.75 95%CI), "lack of energy" (OR=0.54: 0.49
      0.61 95%CI), "lack of willpower" (OR=0.57: 0.51- 0.64 95%CI), "lack of skill"
      (OR=0.76: 0.66-0.87 95%CI) and "lack of resources" (OR=0.79: 0.71-0.89 95%CI).
      Such observation also appeared in the 20- to 23-yearold age group concerning
      "social influence" (OR=0.83: 0.74-0.94 95%CI) and in those aged over 23-years-old
      (OR=0.86: 0.74-0.99 95%CI) regarding "lack of energy". CONCLUSION: A significant
      prevalence was found regarding self-perception of barriers leading to students
      ceasing to engage in PA.

PMID- 25617575
TI  - High-protein diet induces oxidative stress in rat brain: protective action of
      high-intensity exercise against lipid peroxidation.
AB  - INTRODUCTION: It is well established that soy protein diets as well as aerobic
      exercise could promote antioxidant capacity and consequently reduce free radicals
      overproduction on brain. However, little is know regarding to the high-protein
      diets and high intensity exercise on oxidative stress production. The aim of this
      study was to analyse the effects of high-protein diets and high-intensity
      exercise (HIE) on brain oxidative stress markers. MATERIALS AND METHODS: A total
      of 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10):
      normal-protein or high-protein diets with or without HIE for an experimental
      period of 12 weeks. Main oxidative damage markers in brain such as thiobarbituric
      acid-reactive substances (TBARs) and protein carbonyl content (PCC) were
      assessed. In addition, brain manganese superoxide dismutase (Mn-SOD), cooper/
      zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) antioxidant enzymes
      activity, and protein level of Nuclear factor erythroid 2 related factor 2 (Nrf2)
      were measured. RESULTS AND DISCUSSION: Brain TBARs, PCC, tSOD, Mn-SOD, CuZn-SOD
      and CAT levels were higher in the high-protein compared to the normal-protein
      groups (all, p.

PMID- 25617576
TI  - Validity and reliability of the 1/4 mile run-walk test in physically active
      children and adolescents.
AB  - We investigated the criterion-related validity and the reliability of the 1/4
      mile run-walk test (MRWT) in children and adolescents. A total of 86 children
      (n=42 girls) completed a maximal graded treadmill test using a gas analyzer and
      the 1/4MRW test. We investigated the test-retest reliability of the 1/4MRWT in a
      different group of children and adolescents (n=995, n=418 girls). The 1/4MRWT
      time, sex, and BMI significantly contributed to predict measured VO2peak (R2=
      0.32). There was no systematic bias in the cross-validation group (P>0.1). The
      root mean sum of squared errors (RMSE) and the percentage error were 6.9
      ml/kg/min and 17.7%, respectively, and the accurate prediction (i.e. the
      percentage of estimations within +/-4.5 ml/kg/min of VO2peak) was 48.8%. The
      reliability analysis showed that the mean inter-trial difference ranged from 0.6
      seconds in children aged 6-11 years to 1.3 seconds in adolescents aged 12-17
      years (all P. 

PMID- 25617578
TI  - [Nutritional screening in heart failure patients: 5 methods review].
AB  - INTRODUCTION: Malnutrition increases mortality and hospital stay. Increasingly
      Sanitary institutions follow nutritional screening in order to detect early
      malnutrition or the risk of developing. There is not universally accepted method
      for nutritional assessment or screening. OBJECTIVE: Determine a fast and reliable
      method that doesn't require prior training, for the screening and nutritional
      assessment of heart failure's patients. METHOD: Observational study. The
      nutritional status have been evaluated by Subjective global assessment (SGA),
      Mini nutritional assesment (MNA) in his short form (MNA-SF) and in his evaluation
      form (MNA-LF), the nutritional Risk Screnning (NRS 2002), the controlling
      nutritional status or method Ulibarri's method(- CONUT), the Cardona's method and
      the Malnutrition Universal Screening Tool (MUST) the nutritional status of 242
      patients joined in a high complexity hospital with decompensation of chronic
      heart failure. There were analyzed the sensibility, specificity, the predictive
      values, the reasons of verisimilitude, the odds ratio diagnoses and the kappa
      correlation index, of the different methods compared with the subjective global
      valuation, which was considered like gold standard. RESULTS: The mean age was
      75+/-9. The 50,8%(n=123) were men. The kappa index was MNA -LF : 0,637; MNASF:
      0,556; NRS =0,483; MUST =0,197; Cardona =0,188; CONUT =0,076.75. Discusion: Mini
      Nutritional assessment (MNA) was the method that best value offered, both in its
      screening stage of assessment in relation with Subjetive global assesment.

PMID- 25617579
TI  - [Prevalence of malnutrition in a mid-long term stay unit].
AB  - INTRODUCTION: Malnutrition is a common health problem, especially in hospitalized
      patients, where it's associated with longer hospital stays and higher rates of
      morbidity and mortality. Furthermore, current scientific advances and life
      expectancy increase, have produced a progressive increase of mid- to long-term
      stay units (UMLE). AIMS: To determinate the prevalence of malnutrition on
      admission to a mid- to long-term stay unit, using MNA and VGS and to analyze the
      possible factors/clinical features associated with malnutrition and its
      consequences. METHODS: Descriptive and transversal study conducted with 201
      patients admitted consecutively for 12 months in an Universitary Hospital mid- to
      long-term stay unit (Valencia). Clinical, anthropometric, biochemical and
      nutritional history data were registered, as well as Charlson comorbidity scale,
      Pfeiffer cognitive scale, Barthel functional scale and presence of edema, ascitis
      and pressure ulcers. Nutritional status was evaluated in the first 24-72 hours of
      admission using MNA and VGS. Dysphagia was evaluated using EAT-10 and MECV-V
      questionnaires. RESULTS: The overall rate of malnutrition was 76,6%, being severe
      protein energy malnutrition the most common type (20,4%). Malnourished patients
      were older (p=0,002), presented greater dependence (p.

PMID- 25617580
TI  - [Composition and nutritional value of lunches and breakfasts purchased outside
      the households in urban Guatemala].
AB  - The National Survey of Family Income and Expenditure (ENIGFAM 2009-2010), showed
      that a third, and almost two thirds of Guatemalans purchased outside the home
      breakfast and lunch. OBJECTIVE: To determine the composition, nutritional value
      and price of breakfast and lunch menus purchased outside the home in urban areas
      of three departments. METHODOLOGY: A descriptive study. We got nutritional value
      of energy, carbohydrates, proteins and fats, by direct weight of a sample
      selected through convenience in Guatemala, San Marcos and Quetzaltenango. We
      evaluated the nutritional content of 159 breakfasts and 162 lunches, plus
      evaluate nutritional value of 10 complementary recipes by the triplicate recipe
      method. RESULTS: The menus were acquired from Monday to Friday in diners and
      street vendors. The median price was Q9.00 (U.S. $ 1.13) for breakfast and Q12.75
      (U.S. $ 1.59) for lunch. Breakfast ration weighted 425,4g breakfast with 5 or
      more preparations per menu. Lunch weighted 832,5g, with 5 or more preparations
      per menu. At 100 grams, the medians of the nutritional value of breakfast was
      127,5Kcal; 4,0g of protein; 4,2g of fat; 18,7g of carbohydrate; lunch was
      109,3Kcal; 3,8g of protein; fat and 17,3g; 2,7g carbohydrate. It was concluded
      that the menus correspond to the pattern of consumption (or purchase) of the
      Guatemalan population described in the National Basket of Goods and Services and
      in the Basic Food Basket, with high amounts of refined carbohydrates, saturated
      fat and little protein.

PMID- 25617577
TI  - Effect of alpha lipoic acid on the blood cell count and iron kinetics in
      hypertensive patients.
AB  - INTRODUCTION: The ?-lipoic acid (ALA) has been used as a treatment to reduce
      oxidative damage in Systemic Arterial Hypertension (SAH), but there are no in
      vivo studies reporting the effect of its mechanism of action on iron metabolism.
      OBJECTIVE: To evaluate the antioxidant effect of ?-lipoic acid on Blood cell
      count (CBC) and iron metabolism in hypertensive subjects with or without anemia.
      METHOD: Double-blind, randomized, placebo-controlled clinical trial. The sample
      consisted of 60 hypertensive patients that were randomly divided into treatment
      group (n = 32), receiving 600 mg / day of ALA for twelve weeks and control group
      (n = 28), receiving placebo for the same period. Blood cell count, serum iron,
      ferritin, Latent Iron-Binding Capacity (LIBC), Total Iron-Binding Capacity
      (TIBC), Transferrin Saturation Index (TSI) and transferrin were assessed before
      and after intervention. To assess changes between groups, the Student t-test and
      ANOVA were used, adopting a significance level of 5%. RESULTS: After
      intervention, ALA supplementation showed a statistically significant (p < 0.05)
      association with the reduction of total leukocytes, increase in the number of
      neutrophils and reductions in the serum levels of iron and TSI. CONCLUSION: Oral
      administration of ALA as a therapeutic adjuvant changes the hematologic response
      of white blood cells and reduces the absorption of iron. It is observed that the
      mechanism of metals chelation by lipoic acid may be responsible for these changes
      and, consequently, could trigger a condition of iron deficiency anemia in
      hypertensive individuals.

PMID- 25617581
TI  - Nutritional assessment in surgical oncology patients: a comparative analysis
      between methods.
AB  - BACKGROUND AND AIMS: The malnutrition found in oncology patients is the main
      responsible for the increase in morbimortality and worsening of their quality of
      life. Currently, the assessment of malnutrition is performed by subjective and
      objective methods, or the combination of them. Although these methods are
      routinely applied and their association is very common in clinical practice,
      there are few studies on the agreement between them. Thereby, this study aims to
      compare different methods for nutritional status assessment in surgical oncology
      patients. METHODS: 173 oncology patients, admitted for surgery, were submitted to
      an anthropometric evaluation and answered a SGA, PG-SGA and NRS-2002. Kappa test
      was used to evaluated the level of concordance between the methods. RESULTS: Poor
      concordance were observed between BMI and NRS-2002 (K=0,286), SGA (K=0,372) and
      PGSGA (K=0,173). Among the subjective methods, the best results were found for
      SGA and PG-SGA (K=0,690), and the lowest between NRS-2002 and both others (SGA:
      K=0,345; PG-SGA: K=0,322). CONCLUSIONS: The poor concordance found between
      objective and subjective methods reinforces the importance of associating
      indicators in the nutritional assessment of this population Despite of the poor
      concordance found between the nutritional status assessment methods investigated
      in this study, patients who had greater depletion of body stores were also
      diagnosed with a higher degree of malnutrition by subjective methods.

PMID- 25617582
TI  - [Applicability of BMI in adolescent students living at moderate altitude of
      Peru].
AB  - INTRODUCTION AND OBJECTIVES: The use of BMI is highly contested, especially in
      populations in which growth phase is characterized by short stature for his age.
      The aim is to verify if the BMI is applicable to a school sample of adolescents
      living in a region of moderate altitude of Peru. MATERIAL AND METHODS: A
      descriptive cross-sectional study in 319 adolescent students (181 men and 138
      women) from 12.0 to 17.9 years of age. Anthropometric variables of height and
      weight were evaluated. Body Mass Index (BMI) was calculated. The CDC -2000
      reference was used to compare weight and height from Z- score and BMI by mean
      difference. RESULTS: The Z - score showed body weight to small variations (from 
      0.3 to 0.3 kg). In stature negative values for both sexes (men between -0.3 to 
      1.3 cm and women between -0.5 to 1.3 cm) is observed. For BMI, there were
      significant differences in all ages and in both sexes (p.

PMID- 25617583
TI  - [Fatty acid profile of mero (Epinephelus morio) raw and processed oil captured in
      the Yucatan Peninsula, Mexico].
AB  - Unsaturated fatty acids are of current interest for their potential to reduce
      cardiovascular disease, the first cause of death worldwide. By its content of
      essential fatty acids, fish is one of the food products most in demand among the
      population. One of the most popular processes for fish consumption in Yucatan
      Peninsula, Mexico is frying. However, studies show that frying food causes
      changes in the composition generating trans fatty acids. The objective of this
      study was to evaluate the fatty acid profile of Mero (Epinephelus morio) crude
      and processed with different types of commercial oil. The results showed a fat
      content in raw E. morio of 1.68%. The percentage of oil extracted and absorbed by
      the product to be fried with corn oil, sunflower/canola, soybean and safflower
      was found in a range of 2.3-3.93 and 26.95-57.25%, respectively. The lipid
      profile obtained by GC-MS suggested the formation of trans fatty acids by
      isomerization and effect of temperature frying. However essential fatty acids
      such as oleic and linoleic acids were absorbed by E. morio being fried in
      sunflower oil and safflower/ canola, respectively. 

PMID- 25617584
TI  - Differences in food intake and nutritional habits between Spanish adolescents who
      engage in ski activity and those who do not.
AB  - BACKGROUND: Increasing obesity among adolescents in the industrialized world may
      result from poor nutritional habits and inadequate exercise. AIM: To determine
      differences in food intake, nutritional habits, and body mass index between
      Spanish adolescents who engage in ski activity and those who do not. METHODS: A
      socio-demographic survey, food frequency questionnaire, 24-hr dietary recall, and
      physical activity questionnaire were completed by 300 Spanish schoolchildren aged
      10 to 18 yrs. RESULTS were compared (Student's t, chi-square and Fisher's exact
      test) between adolescents engaged (SP) and not engaged (N-SP) in skiing according
      to their sex. RESULTS: SP adolescents devoted > 4 h/day to physical activity
      versus < 1 h for N-SP adolescents. No significant differences were found in
      nutrient intake or nutritional habits between SP and N-SP adolescents. Protein
      and fat intakes of both groups were above recommended levels. A higher proportion
      of N-SP than SP males were overweight. Logistic regression analysis showed that
      the maintenance of a normal weight was favored by the practice of skiing, the
      consumption of sugar-free drinks, and supplementation with vitamins/mineral salts
      and was negatively associated with body weight dissatisfaction, intake of
      nutritional supplements other than vitamins or minerals, and the consumption of
      snacks. CONCLUSIONS: The diet of this adolescent population was poorly balanced.
      Engagement in physical activity appears to be a key factor in maintaining a
      healthy body mass index.

PMID- 25617585
TI  - Mites and the implications on human health.
AB  - INTRODUCTION: The infestation by mites of stored products is of great economic
      importance and public health, with consequences to human health. OBJECTIVES: To
      describe the mite species associated to food and stored products that cause
      implications to human health as well as to analyze the loss of quality and
      nutritional composition of infested food. METHOD: Literature review in LILACS
      BIREME, SciELO and MEDLINE databases for publications in English, Portuguese and
      Spanish with the descriptors "mites", "foods", "storage mites", "store product
      mites", "dust mites", "quality control", "quality foods", "chemical composition",
      "chemistry", "allergens" and "health". There were identified 80 articles, but
      only 55 were related to the objectives of the study. Sixteen references were
      mentioned in the articles that were found after checked for relevance. RESULTS
      AND DISCUSSION: The activity of the mites causes loss of sanitary quality, weight
      and nutritional composition of the infested products, with great economic loss in
      the grain industry. Inhalation, ingestion or contact of mites, byproducts of
      metabolism and feces may sensitize susceptible individuals and cause asthma,
      allergic rhinitis, contact dermatitis, enteritis and lead to anaphylaxis. The
      monitoring of temperature and humidity is essential for the control of mites, as
      well as better conservation and hygiene of the units of grain storage.

PMID- 25617586
TI  - [Quality of life and its determinants in Spanish university students of health
      sciences factors].
AB  - INTRODUCTION: The quality of life of university students acquires special
      importance because it provides information about their life conditions and
      especially how they perceive it. OBJECTIVE: Evaluate the quality of life of
      students who are enrolled in health science studies and its relation with the
      following diverse factors: life and dietetic habits, anthropometric parameters
      and the influence of distinct variables on their perception. METHODS: Transversal
      study of a sample of 1753 health science degree students of nine Spanish
      universities with a randomized design and stratified by course and faculty for
      which we applied an ad hoc questionnaire that considered all study variables.
      RESULTS: The quality of life (QoL) perceived by the participants had a Median of
      75. The factors that were explored about the quality of life correlated
      significantly with their global perception of it (p.

PMID- 25617587
TI  - [Consumption of carbonated beverages with nonnutritive sweeteners in Latin
      American university students].
AB  - INTRODUCTION: Consumption of carbonated beverages with nonnutritive sweeteners
      (NNS) is increasingly common in order to maintain a healthy weight, but the
      effect of NNS on body weight is controversial. MATERIALS AND METHODS: University
      students (n=1,229) of both sexes aged 18 to 26, of which 472 were from Chile, 300
      of Panama, 253 from Guatemala and 204 of Peru. Each student was applied a
      frequency survey of weekly food consumption supported by photographs of beverages
      with NNS from each country to determine the intake of them. Also they underwent
      anthropometric measurements. RESULTS: 80% of these students consumed carbonated
      beverages with NNS, none of them exceeded the acceptable daily intake for
      sucralose, potassium acesulfame and aspartame. Increased consumption in both men
      and women was observed in chilean students (p.

PMID- 25617588
TI  - [Comparative study of habits in students before and during the university in
      northwest area of Madrid].
AB  - INTRODUCTION: In most Western countries young people adopt lifestyles that
      adversely affect their health, thus increasing the risk of premature onset of
      chronic diseases. Therefore, the aim of this study was to compare patterns of
      habits in pre-university and university students in west-central area of Madrid.
      MATERIALS AND METHODS: Descriptive longitudinal study with randomly selected
      students from Madrid in Madrid universities and schools-institutes. Accepting to
      participate 1590 students of both sex: 653 males (4,1%) and 937 women (58,9%). To
      facilitate the study were classified into <= 17 years (pre university) and >= 18
      years (university). RESULTS: BMI, physical activity, alcohol consumption and
      negative habits with regard to food consumption was studied. Almost 80% have
      normal weight, are more active pre-university. CONCLUSIONS: Gender differences
      were observed, which should guide the actions of intervention in terms of
      physical activity or habits. It seems essential to make nutritional programs as
      well as psychosocial intervention in adolescents and youth to prevent and / or
      reduce alcohol consumption.

PMID- 25617589
TI  - [The university stage does not favor the healthy life style in women students
      from Granada].
AB  - OBJECTIVE: The university stage involves a series of emotional, physiological and
      environmental changes that will determine consumer patterns that, in many cases,
      will be maintained and will affect their health. The aim of this study is to
      analyze the lifestyle (alcohol and tobacco consumption, and levels of physical
      activity) of female students at the University of Granada. Several authors have
      noted that the student population is particularly vulnerable to develop risk
      customs and habits, since the period of university studies is often the time when
      students take first responsibility for determining their own styles and customs,
      which in many cases will be maintained throughout its entire life. METHODOLOGY:
      This is a cross / descriptive and analytical study in which 55 students
      participated in two age groups (18-24 and 25-31 years). A lifestyle-questionnaire
      was applied to evaluate the type and frequency of alcohol consumption, number of
      cigarettes smoked daily and physical activity levels (sedentary, light, moderate
      and severe). RESULTS: Alcohol consumption is higher in the older group, and
      preferably drinks beer and wine; however the younger group shows a pattern of
      consumption centered on the weekends being preferably consumed distilled
      beverages. A third of the population smokes with an increase in the number of
      cigarettes as age increases. There is a positive correlation between snuff and
      alcohol. A direct positive correlation between tobacco and alcohol was observed.
      The 88.9% of lesser age group and 52.7% of higher age group show a sedentary-low
      physical activity. CONCLUSION: The need to sensitize the college female
      population on the benefits of no-consumption of alcohol and snuff, and regular
      physical exercise is suggested. It would also be advisable to develop protocols
      of educational intervention in universities promoting healthy living habits.

PMID- 25617590
TI  - [Nutritional care protocol proposal for patients living with HIV without
      antiretroviral therapy, treated at the center of diagnostic references of San
      Martin de Quillota Hospital, Chile].
AB  - BACKGROUND: The nutritional care for HIV patients in Chile is a challenge for
      public health due to the absence of ministerial guidelines to ensure standardized
      and timely nutritional care that helps to enhance immunity and delay
      immunological failure from a preventive approach. OBJECTIVE: To design a proposal
      of protocol for nutritional care to optimize the nutritional management in a
      group of patients living with HIV. METHODOLOGY: The design considered an initial
      diagnosis (patients and nutritional care characterization in a secondary public
      health service) to identify local needs, which was complemented with
      bibliographical precedents. Protocol content was validated by expert opinion,
      using a Likert questionnaire evaluating three variables: format, protocol's plan
      of nutritional care, and content quality. RESULTS: The proposed protocol consists
      of flowcharts care, nutritional care procedures and educational material. The
      validation process involved five experts, according to whom more time for patient
      care should be assigned, integration of the multidisciplinary team should be
      consider in the flowcharts and in short term reliability and applicability of the
      protocol should be assessed. DISCUSSION: This proposal is the first document
      oriented to nutritional management of outpatient with HIV from the early stages
      of the disease in Chile. Studies are needed to measure the impact of nutritional
      intervention in patients with HIV without antiretroviral therapy.

PMID- 25617591
TI  - [Hyperemesis gravidarum: management and nutritional implications; case report and
      review of literature].
AB  - INTRODUCTION: Hyperemesis gravidarum is a state of severe nausea and vomiting
      during pregnancy, leading to dehydration, electrolyte and acid-base disorders,
      malnutrition and weight loss (> 5%). The prevalence of hyperemesis gravidarum is
      0.3-2.3% of all pregnancies. OBJECTIVE: To demonstrate the effectiveness of
      nutritional support in a case of a complicated hyperemesis gravidarum. A case of
      a 25 years old woman with hyperemesis gravidarum, who had weight loss of 17.7%,
      dehydration, electrolyte disorders and arrhythmias, managed with enteral and
      parenteral nutrition at home until week 26 of gestation reaching to cover 70% of
      her caloric requirements orally, getting a healthy product and a stable
      nutritionally mother in late pregnancy. CONCLUSIONS: The multidisciplinary
      management and specialized nutritional management in such cases it is compulsory
      to carry the patient and the product at the end of pregnancy in optimal
      conditions.

PMID- 25617593
TI  - How big is this sound? Crossmodal association between pitch and size in infants.
AB  - We examined 4- and 6-month-old infants' sensitivity to the perceptual association
      between pitch and object size. Crossmodal correspondence effects were observed in
      6-month-old infants but not in younger infants, suggesting that experience and/or
      further maturation is needed to fully develop this crossmodal association. 

PMID- 25617592
TI  - The lipid peroxidation product 4-hydroxy-trans-2-nonenal causes protein synthesis
      in cardiac myocytes via activated mTORC1-p70S6K-RPS6 signaling.
AB  - Reactive oxygen species (ROS) are elevated in the heart in response to
      hemodynamic and metabolic stress and promote hypertrophic signaling. ROS also
      mediate the formation of lipid peroxidation-derived aldehydes that may promote
      myocardial hypertrophy. One lipid peroxidation by-product, 4-hydroxy-trans-2
      nonenal (HNE), is a reactive aldehyde that covalently modifies proteins thereby
      altering their function. HNE adducts directly inhibit the activity of LKB1, a
      serine/threonine kinase involved in regulating cellular growth in part through
      its interaction with the AMP-activated protein kinase (AMPK), but whether this
      drives myocardial growth is unclear. We tested the hypothesis that HNE promotes
      myocardial protein synthesis and if this effect is associated with impaired LKB1
      AMPK signaling. In adult rat ventricular cardiomyocytes, exposure to HNE (10 MUM
      for 1h) caused HNE-LKB1 adduct formation and inhibited LKB1 activity. HNE
      inhibited the downstream kinase AMPK, increased hypertrophic mTOR-p70S6K-RPS6
      signaling, and stimulated protein synthesis by 27.1 +/- 3.5%. HNE also stimulated
      Erk1/2 signaling, which contributed to RPS6 activation but was not required for
      HNE-stimulated protein synthesis. HNE-stimulated RPS6 phosphorylation was
      completely blocked using the mTOR inhibitor rapamycin. To evaluate if LKB1
      inhibition by itself could promote the hypertrophic signaling changes observed
      with HNE, LKB1 was depleted in adult rat ventricular myocytes using siRNA. LKB1
      knockdown did not replicate the effect of HNE on hypertrophic signaling or affect
      HNE-stimulated RPS6 phosphorylation. Thus, in adult cardiac myocytes HNE
      stimulates protein synthesis by activation of mTORC1-p70S6K-RPS6 signaling most
      likely mediated by direct inhibition of AMPK. Because HNE in the myocardium is
      commonly increased by stimuli that cause pathologic hypertrophy, these findings
      suggest that therapies that prevent activation of mTORC1-p70S6K-RPS6 signaling
      may be of therapeutic value.

PMID- 25617594
TI  - The joint influence of acquired capability for suicide and stoicism on over
      exercise among women.
AB  - We investigated longitudinal relationships among eating disorder behaviors,
      stoicism, and the acquired capability for suicide (ACS), which is a construct
      comprised of pain tolerance and fearlessness about death. University students
      (n=150) completed assessments measuring stoicism, ACS, and eating disorder
      behaviors at two time points approximately 30days apart. Among women, there was a
      quadratic relationship between ACS and over-exercise behaviors, such that as ACS
      increased the positive association between ACS and over-exercise became more
      pronounced. Further, among women, ACS moderated the relationship between stoicism
      and over-exercise, such that high levels of ACS in combination with stoicism
      predicted increases in over-exercise. Results suggest that ACS in combination
      with stoicism may lead women to engage in more eating disordered behaviors, like
      over-exercise. 

PMID- 25617595
TI  - Opposite effects of oxytocin on water intake induced by hypertonic NaCl or
      polyethylene glycol administration.
AB  - Oxytocin (OT), a neurohormone, has been related to natriuretic and diuretic
      effects and also to water intake and sodium appetite. The objective of the
      present study was to determine the effect of subcutaneous OT administration on
      water intake and urine-related measures induced by the administration of
      hypertonic NaCl (experiment 1) or polyethylene glycol (PEG) (experiment 2).
      Experiment 1 showed that OT administration increases the urine volume, urinary
      sodium concentration, and natriuresis and reduces the water intake, water and
      sodium balances, and estimated plasma sodium concentration induced by hypertonic
      NaCl administration. Conversely, experiment 2 showed that OT administration
      increases the water intake and the antidiuretic response induced by PEG
      administration. These results show that the opposite effects of OT on the water
      intake induced by hypertonic NaCl or PEG administration are accompanied by
      differential regulatory effects, enhancing a natriuretic response in the first
      experiment and generating an antidiuretic reaction in the second experiment. This
      study suggests a differential regulatory effect of OT during states of intra- and
      extracellular thirst. 

PMID- 25617596
TI  - Effects of microcystin-LR on bacterial and fungal functional genes profile in rat
      gut.
AB  - The short-term exposure to microcystin-LR (MC-LR, one of the most common and
      toxic variants generated by toxigenic cyanobacteria) induced gut dysfunction such
      as generation of reactive oxygen species, cell erosion and deficient intestinal
      absorption of nutrients. However, till now, little is known about its impact on
      gut microbial community, which has been considered as necessary metabolic
      assistant and stresses resistant entities for the host. This study was designed
      to reveal the shift of microbial functional genes in the gut of rat orally
      gavaged with MC-LR. GeoChip detected a high diversity of bacterial and fungal
      genes involved in basic metabolic processes and stress resistance. The results
      showed that the composition of functional genes was significantly changed in rat
      gut after one week of exposure to MC-LR, and we found some relatively enriched
      genes that are involved in carbon degradation including chitin, starch and
      limonene metabolism, and these genes were mainly derived from fungal and
      bacterial pathogens. In addition, we found large amounts of significantly
      enriched genes relevant to degradation of the specific carbon compounds,
      aromatics. The dysbiosis of bacterial and fungal flora gave an implication of
      pathogens invasion. The enriched gene functions could be linked to acute
      gastroenteritis induced by MC-LR. 

PMID- 25617597
TI  - Pharmacological characterization of conotoxin lt14a as a potent non-addictive
      analgesic.
AB  - Conotoxin lt14a is a small peptide consisting of 13 amino acids. It was
      originally identified from the cDNA of Conus litteratus in the South China Sea.
      Previous reports showed lt14a exhibited antinociceptive activity using a hot
      plate-induced pain mouse model and acted as an antagonist of neuronal nicotinic
      acetylcholine receptors. We confirmed that conotoxin lt14a administration
      resulted in antinociception activity using a mouse inflammatory pain model and a
      rat model of mechanically-induced pain. The mRNA expression of c-fos and NOS in
      the spinal cord of rats was suppressed by lt14a. Labeling of lt14a with an Alexa
      Fluor 488 ester showed that lt14a was bound to the surface of PC12 cells and that
      this binding was inhibited by pre-application of the nicotinic acetylcholine
      receptor (nAChR) antagonist tubocurarine chloride (TUB) and the nAChR blocker
      hexamethonium bromide (HB). These data confirm previous reports that showed lt14a
      binds to the surface of PC12 cells via nAChRs with patch clamp whole-cell
      recordings. Additional results showed that lt14a suppressed extracellular signal
      regulated kinase (ERK1/2) phosphorylation in PC12 cells activated by Ach. Our
      results showed that lt14a did not induce drug dependence but rather suppressed
      morphine withdrawal symptoms. Our work suggests that lt14a is a novel
      antinociceptive agent that targets the nAChR receptor without inducing drug
      dependence. 

PMID- 25617598
TI  - Targeting extrinsic apoptosis in cancer: Challenges and opportunities.
AB  - Apoptosis is a form of programmed cell death that plays a critical role in the
      regulation of various physiological and pathophysiological processes. Since
      apoptosis is typically disturbed in human cancers, therapeutic targeting of
      apoptosis represents a promising avenue for the development of novel therapeutic
      approaches. This strategy is particularly relevant, since many currently used
      anticancer therapies utilize apoptosis signaling pathways to exert their
      antitumor activities. A better understanding of these signaling networks and
      their deregulation in human cancers is anticipated to open new perspectives for
      the development of apoptosis-targeted therapies for the treatment of cancer. 

PMID- 25617599
TI  - Getting a handle on embryo limb development: Molecular interactions driving limb
      outgrowth and patterning.
AB  - Development of the vertebrate embryo involves multiple segmentation processes to
      generate a functional, articulated organism. Cell proliferation, differentiation
      and patterning involve spatially and temporally regulated gene expression and
      signal transduction mechanisms. The developing vertebrate limb is an excellent
      model to study such fine-tuned regulations, whereby cells proliferate and are
      differentially sculptured along the proximal-distal, anterior-posterior and
      dorsal-ventral axes to form a functional limb. Complementary experimental
      approaches in different organisms have enhanced our knowledge on the molecular
      events underlying limb development. Herein, we summarize the current knowledge of
      the main signaling mechanisms governing vertebrate limb initiation, outgrowth,
      specification of limb segments and termination. 

PMID- 25617601
TI  - Measuring personal heat exposure in an urban and rural environment.
AB  - Previous studies have linked heat waves to adverse health outcomes using ambient
      temperature as a proxy for estimating exposure. The goal of the present study was
      to test a method for determining personal heat exposure. An occupationally
      exposed group (urban groundskeepers in Birmingham, AL, USA N=21), as well as
      urban and rural community members from Birmingham, AL (N=30) or west central AL
      (N=30) wore data logging temperature and light monitors clipped to the shoe for 7
      days during the summer of 2012. We found that a temperature monitor clipped to
      the shoe provided a comfortable and feasible method for recording personal heat
      exposure. Ambient temperature ( degrees C) recorded at the nearest weather
      station was significantly associated with personal heat exposure [beta 0.37,
      95%CI (0.35, 0.39)], particularly in groundskeepers who spent more of their total
      time outdoors [beta 0.42, 95%CI (0.39, 0.46)]. Factors significantly associated
      with lower personal heat exposure include reported time indoors [beta -2.02,
      95%CI (-2.15, -1.89)], reported income>20K [beta -1.05, 95%CI (-1.79, -0.30)],
      and measured % body fat [beta -0.07, 95%CI (-0.12, -0.02)]. There were
      significant associations between income and % body fat with lower indoor and
      nighttime exposures, but not with outdoor heat exposure, suggesting modifications
      of the home thermal environment play an important role in determining overall
      heat exposure. Further delineation of the effect of personal characteristics on
      heat exposure may help to develop targeted strategies for preventing heat-related
      illness. 

PMID- 25617602
TI  - Zinc treatment prevents type 1 diabetes-induced hepatic oxidative damage,
      endoplasmic reticulum stress, and cell death, and even prevents possible
      steatohepatitis in the OVE26 mouse model: Important role of metallothionein.
AB  - Whether zinc is able to improve diabetes-induced liver injury remains unknown.
      Transgenic type 1 diabetic (OVE26) mice develop hyperglycemia at 3 weeks old;
      therefore therapeutic effect of zinc on diabetes-induced liver injury was
      investigated in OVE26 mice. Three-month old OVE26 and age-matched wild-type mice
      were treated by gavage with saline or zinc at 5mg/kg body-weight every other day
      for 3 months. Hepatic injury was examined by serum alanine aminotransferase (ALT)
      level with liver histopathological and biochemical changes. OVE26 mice at 6
      months old showed significant increases in serum ALT level and hepatic oxidative
      damage, endoplasmic reticulum stress and associated cell death, mild
      inflammation, and fibrosis. However, all these hepatic morphological and
      functional changes were significantly prevented in 3-month zinc-treated OVE26
      mice. Mechanistically, zinc treatment significantly increased hepatic
      metallothionein, a protein with known antioxidant activity, in both wild-type and
      OVE26 mice. These results suggest that there were significantly functional,
      structural and biochemical abnormalities in the liver of OVE26 diabetic mice at 6
      months old; however, all these changes could be prevented with zinc treatment,
      which was associated with the upregulation of hepatic metallothionein expression.

PMID- 25617600
TI  - Emerging trends in the pathophysiology of lymphatic contractile function.
AB  - Lymphatic contractile dysfunction is central to a number of pathologies that
      affect millions of people worldwide. Due to its critical role in the process of
      inflammation, a dysfunctional lymphatic system also compromises the immune
      response, further exacerbating a number of inflammation related diseases. Despite
      the critical physiological functions accomplished by the transport of lymph, a
      complete understanding of the contractile machinery of the lymphatic system lags
      far behind that of the blood vasculature. However, there has been a surge of
      recent research focusing on different mechanisms that underlie both physiological
      and pathophysiological aspects of lymphatic contractile function. This review
      summarizes those emerging paradigms that shed some novel insights into the
      contractile physiology of the lymphatics in normal as well as different disease
      states. In addition, this review emphasizes the recent progress made in our
      understanding of various contractile parameters and regulatory elements that
      contribute to the normal functioning of the lymphatics. 

PMID- 25617603
TI  - Evaluating degradation of hexachlorcyclohexane (HCH) isomers within a
      contaminated aquifer using compound-specific stable carbon isotope analysis
      (CSIA).
AB  - The applicability of compound-specific stable carbon isotope analysis (CSIA) for
      assessing biodegradation of hexachlorocyclohexane (HCH) isomers was investigated
      in a contaminated aquifer at a former pesticide processing facility. A CSIA
      method was developed and tested for efficacy in determining carbon isotope ratios
      of HCH isomers in groundwater samples using gas chromatography - isotope ratio
      mass spectrometry (GC-IRMS). The carbon isotope ratios of HCHs measured for
      samples taken from the field site confirmed contaminant source zones at former
      processing facilities, a storage depot and a waste dump site. The (13)C
      enrichment in HCHs provided evidence for biodegradation of HCHs especially
      downstream of the contaminant source zones. CSIA from monitoring campaigns in
      2008, 2009 and 2010 revealed temporal trends in HCH biodegradation. Thus, the
      impact and progress of natural attenuation processes could be evaluated within
      the investigated aquifer. Calculations based on the Rayleigh-equation approach
      yielded levels of HCH biodegradation ranging from 30 to 86 %. Moreover, time- and
      distance-dependent in situ first-order biodegradation rate constants were
      estimated with maximal values of 3 * 10(-3) d(-1) and 10 * 10(-3) m(-1) for alpha
      HCH, 11 * 10(-3) d(-1) and 37 * 10(-3) m(-1) for beta-HCH, and 6 * 10(-3) d(-1)
      and 19 * 10(-3) m(-1) for delta-HCH, respectively. This study highlights the
      applicability of CSIA for the assessment of HCH biodegradation within
      contaminated aquifers. 

PMID- 25617604
TI  - Letter to the Editor in response to "publication performance of women compared to
      men in German cardiology" by Boehm et al. (2014).
AB  - Based on their review of abstracts submitted to the German Cardiac Society, Boehm
      et al. (2014) report better success of female vs male cardiologists publishing in
      journals with an impact factor >=5. However, only 25% of conference abstracts
      were submitted by women, perhaps suggesting a paucity of women in academic
      cardiology. In this 'letter to the editor' we review gender statistics in the
      medical field using Germany and the US as examples. While women are well
      represented in early career stages, only fewfull professors are women. This
      reflects a wasted opportunity to benefit from the best of both genders. Recent
      gender research has shown that subtle gender bias may play a role. To change the
      gender statistics in academic medicine a multifaceted approach is necessary. This
      will ultimately lead to a more equal representation of women in senior roles, and
      bring science, medical care, and leadership to a new level. 

PMID- 25617605
TI  - Tumor necrosis factor-alpha antagonism with etanercept improves endothelial
      progenitor cell counts in patients with psoriasis: etanercept, vascular function
      and endothelial progenitor cells in psoriasis.

PMID- 25617606
TI  - Dual chamber cardioverter-defibrillator used for His bundle pacing in patient
      with chronic atrial fibrillation.

PMID- 25617607
TI  - Progression rates of apical aneurysm and dynamic obstruction in mid-ventricular
      hypertrophic cardiomyopathy: can we recognize a 'benign trend'?

PMID- 25617608
TI  - Myocardial viability for decision-making concerning revascularization in patients
      with left ventricular dysfunction and coronary artery disease: a meta-analysis of
      non-randomized and randomized studies.
AB  - BACKGROUND: Myocardial viability tests have been proposed as a key factor in the
      decision-making process concerning coronary revascularization procedures in
      patients with left ventricular dysfunction and coronary artery disease (LVD-CAD).
      METHODS: We performed a systematic review and meta-analysis of studies that
      compared medical treatment with revascularization in patients with viable and non
      viable myocardium and recorded mortality as outcome. RESULTS: Thirty-two non
      randomized (4328 patients) and 4 randomized (1079 patients) studies were
      analyzed. In non-randomized studies, revascularization provided a significant
      mortality benefit compared with medical treatment (p<0.05). Since the
      heterogeneity was significant (p<0.05) a viability subgroup analysis was
      performed, showing that revascularization provided a significant mortality
      benefit compared with medical treatment in patients with viable myocardium
      (p<0.05) but not in patients without (p=0.34). There was a significant subgroup
      effect (p<0.05) related to the intensity of the effect, but not to the direction.
      In randomized studies, revascularization did not provide a significant mortality
      benefit compared with medical treatment in either patients with viable myocardium
      or those without (p=0.21). There was no significant subgroup effect (p=0.72).
      Neither non-randomized nor randomized studies demonstrated any significant
      difference in outcomes between patients with and without viable myocardium.
      CONCLUSIONS: The available data are inconclusive regarding the usefulness of
      myocardial viability tests for the decision-making process concerning
      revascularization in LVD-CAD patients. Patients with viable myocardium appear to
      benefit from revascularization, but similar benefits were observed in patients
      without viable myocardium. Moreover, a neutral or adverse effect of
      revascularization cannot be excluded in either group of patients.

PMID- 25617609
TI  - Using comparative genomics to drive new discoveries in microbiology.
AB  - Bioinformatics looks to many microbiologists like a service industry. In this
      view, annotation starts with what is known from experiments in the lab, makes
      reasonable inferences of which genes match other genes in function, builds
      databases to make all that we know accessible, but creates nothing truly new.
      Experiments lead, then biocuration and computational biology follow. But the
      astounding success of genome sequencing is changing the annotation paradigm.
      Every genome sequenced is an intercepted coded message from the microbial world,
      and as all cryptographers know, it is easier to decode a thousand messages than a
      single message. Some biology is best discovered not by phenomenology, but by
      decoding genome content, forming hypotheses, and doing the first few rounds of
      validation computationally. Through such reasoning, a role and function may be
      assigned to a protein with no sequence similarity to any protein yet studied.
      Experimentation can follow after the discovery to cement and to extend the
      findings. Unfortunately, this approach remains so unfamiliar to most bench
      scientists that lab work and comparative genomics typically segregate to
      different teams working on unconnected projects. This review will discuss several
      themes in comparative genomics as a discovery method, including highly derived
      data, use of patterns of design to reason by analogy, and in silico testing of
      computationally generated hypotheses. 

PMID- 25617610
TI  - Fabrication of high specificity hollow mesoporous silica nanoparticles assisted
      by Eudragit for targeted drug delivery.
AB  - Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising
      carriers for effective drug delivery due to their large surface area, high volume
      for drug loading and excellent biocompatibility. However, the non-ionic
      surfactant templated HMSNs often have a broad size distribution and a defective
      mesoporous structure because of the difficulties involved in controlling the
      formation and organization of micelles for the growth of silica framework. In
      this paper, a novel "Eudragit assisted" strategy has been developed to fabricate
      HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self
      assembly of micelle organisation. Highly dispersed mesoporous silica spheres with
      intact hollow interiors and through pores on the shell were fabricated. The HMSNs
      have a high surface area (670 m(2)/g), small diameter (120 nm) and uniform pore
      size (2.5 nm) that facilitated the effective encapsulation of 5-fluorouracil
      within HMSNs, achieving a high loading capacity of 194.5 mg(5-FU)/g(HMSNs). The
      HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be
      bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell
      internalization. The high specificity and excellent targeting performance of EGF
      grafted HMSNs have demonstrated that they can become potential intracellular drug
      delivery vehicles for colorectal cancers via EGF-EGFR interaction.

PMID- 25617611
TI  - Cellulose nanofibrils for one-step stabilization of multiple emulsions (W/O/W)
      based on soybean oil.
AB  - Cellulose nanofibrils (CNF) were incorporated in water-in-oil (W/O)
      microemulsions and emulsions, as well as water-in-oil-in-water (W/O/W) multiple
      emulsions using soybean oil. The addition of CNF to the aqueous phase expanded
      the composition range to obtain W/O/W emulsions. CNF also increased the viscosity
      of the continuous phase and reduced the drop size both of which increased the
      stability and effective viscosity of the emulsions. The effects of oil type and
      polarity on the properties of the W/O/W emulsions were tested with limonene and
      octane, which compared to soybean oil produced a smaller emulsion drop size, and
      thus a higher emulsion viscosity. Overall, CNF are a feasible alternative to
      conventional polysaccharides as stability enhancers for normal and multiple
      emulsions that exhibit strong shear thinning behavior. 

PMID- 25617612
TI  - Control of particle size by feed composition in the nanolatexes produced via
      monomer-starved semicontinuous emulsion copolymerization.
AB  - Conventional batch and semicontinuous emulsion copolymerizations often produce
      large particles whose size cannot be easily correlated with the comonomer feed
      compositions, and are to some degree susceptible to composition drift. In
      contrast, we found that copolymer nanolatexes made via semicontinuous monomer
      starved emulsion copolymerizations are featured with an average nanoparticle size
      being controlled by the feed composition, a high conversion achieved, and a high
      degree of particle composition uniformity. This was achieved because the rate of
      particle growth, during nucleation, was controlled by the rate of comonomer
      addition, and the copolymer composition, surfactant parking area on the
      particles, and nucleation efficiency determined by the comonomer feed
      composition. Two model systems, methyl methacrylate/styrene and vinyl
      acetate/butyl acrylate, with significant differences in water solubility were
      studied. Monomers were added to the aqueous solution of sodium dodecylsulfate and
      potassium persulfate at a low rate to achieve high instantaneous conversions. 

PMID- 25617613
TI  - Preparation of nanoemulsions containing unsaturated fatty acid concentrate
      chitosan capsules.
AB  - HYPOTHESIS: Fish oil is rich in unsaturated fatty acids (omega-3), which are
      highly susceptible to oxidative degradation. The use of encapsulation process to
      retard the fatty acid oxidation is an interesting alternative. In this work,
      nanoemulsions containing capsules of unsaturated fatty acids concentrate (UFAC)
      using chitosan as wall material were prepared and characterized. EXPERIMENTS: The
      UFAC were obtained from carp viscera and chitosan was obtained from shrimp
      wastes. The nanocapsules were prepared by the emulsion method. Four formulations
      were tested, using different combinations of chitosan concentration and
      homogenization times. In the more suitable conditions, the emulsion was freeze
      dried to obtain a microstructure with capacity to increase the capsules
      stability. FINDINGS: The results showed that the nanocapsules presented a
      spherical shape. The use of low wall material concentration and high
      homogenization time provided nanocapsules with smallest size (332 nm) and lowest
      polydispersity index (0.214). The microstructure obtained by freeze drying was
      irregular and porous. The peroxide values demonstrated that the microstructure
      was able to protect the UFAC regarding to primary oxidation. The encapsulation
      efficiency was 74.1%, showing that chitosan has potential to be used as
      encapsulating agent for unsaturated fatty acid concentrate (UFAC).

PMID- 25617614
TI  - Enhanced capacitive deionization performance of graphene by nitrogen doping.
AB  - Nitrogen-doped graphene (NG) was fabricated via a simple thermal treatment of
      graphene oxide in an ammonia atmosphere. The morphology, structure and
      electrochemical performance of NG were characterized by scanning electron
      microscopy, Raman spectroscopy, nitrogen adsorption-desorption, X-ray
      photoelectron spectroscopy, cyclic voltammetry and electrochemical impedance
      spectroscopy. The electrosorption performance of NG in NaCl solution was studied
      and compared with pristine graphene (PG). The results show that due to its high
      specific surface area, increased specific capacitance and low charge transfer
      resistance, NG exhibits high electrosorption capacity of 4.81 mg g(-1) when the
      initial solution conductivity is 100 MUS cm(-1), which are much higher than those
      of PG (3.85 mg g(-1)).

PMID- 25617615
TI  - Total synthesis of isotopically enriched Si-29 silica NPs as potential spikes for
      isotope dilution quantification of natural silica NPs.
AB  - A new method was developed for the preparation of highly monodisperse
      isotopically enriched Si-29 silica nanoparticles ((29)Si-silica NPs) with the
      purpose of using them as spikes for isotope dilution mass spectrometry (IDMS)
      quantification of silica NPs with natural isotopic distribution. Si-29 tetraethyl
      orthosilicate ((29)Si-TEOS), the silica precursor was prepared in two steps
      starting from elementary silicon-29 pellets. In the first step Si-29 silicon
      tetrachloride ((29)SiCl4) was prepared by heating elementary silicon-29 in
      chlorine gas stream. By using a multistep cooling system and the dilution of the
      volatile and moisture-sensitive (29)SiCl4 in carbon tetrachloride as inert medium
      we managed to reduce product loss caused by evaporation. (29)Si-TEOS was obtained
      by treating (29)SiCl4 with absolute ethanol. Structural characterisation of
      (29)Si-TEOS was performed by using (1)H and (13)C nuclear magnetic resonance
      (NMR) spectroscopy and Fourier-transform infrared (FTIR) spectroscopy. For the NP
      preparation, a basic amino acid catalysis route was used and the resulting NPs
      were analysed using transmission electron microscopy (TEM), small angle X-ray
      scattering (SAXS), dynamic light scattering (DLS) and zeta potential
      measurements. Finally, the feasibility of using enriched NPs for on-line field
      flow fractionation coupled with multi-angle light scattering and inductively
      coupled plasma mass spectrometry (FFF/MALS/ICP-MS) has been demonstrated. 

PMID- 25617616
TI  - Molecular cloning and characterization of a beta-1,3-glucan recognition protein
      from Plutella xylostella (L.).
AB  - The beta-glucan recognition proteins (betaGRPs) play a significant role as
      important pattern recognition proteins (PRPs) for recognizing conserved surface
      determinants of pathogens and trigger complex signaling pathways in
      invertebrates. In the present study, a full-length cDNA 1793bp encoding 479 amino
      acids and betaGRP1 was obtained from Plutella xylostella by reverse transcription
      PCR (RT-PCR) (designed as P*betaGRP1) which showed significant similarities with
      other insect's betaGRPs. The transcription level was constitutively expressed and
      upregulated by microbial induction in all life stages of P. xylostella. Tissue
      distribution showed P*betaGRP1 to be mainly expressed in fat body as detected by
      quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Subsequent to
      knock down the P*betaGRP1 expression and the transcripts of Toll-like receptor,
      cecropin 1 and cecropin 2 decreased in P. xylostella. Meanwhile, the bacterial
      colonies increased and the expression of four AMP genes decreased on injection of
      anti-P*betaGRP1 into Bombyx mori. The results demonstrated that P*betaGRP1 can
      play a vital role in response to the expression of AMP genes in P. xylostella. 

PMID- 25617617
TI  - Investigations of blue light-induced reactive oxygen species from flavin
      mononucleotide on inactivation of E. coli.
AB  - The micronutrients in many cellular processes, riboflavin, flavin mononucleotide
      (FMN), and flavin adenine dinucleotide (FAD) are photo-sensitive to UV and
      visible light for generating reactive oxygen species (ROS). Produced from
      phosphorylation of riboflavin, FMN is more water-soluble and rapidly transformed
      into free riboflavin after ingestion. This study investigated the application of
      visible blue light with FMN to development of an effective antimicrobial
      treatment. The photosensitization of bacterial viability with FMN was
      investigated by light quality, intensity, time, and irradiation dosage. The blue
      light-induced photochemical reaction with FMN could inactivate Escherichiacoli by
      the generated ROS in damaging nucleic acids, which was validated. This novel
      photodynamic technique could be a safe practice for photo-induced inactivation of
      environmental microorganism to achieve hygienic requirements in food processing. 

PMID- 25617618
TI  - Serum visfatin concentration in acutely ill and weight-recovered patients with
      anorexia nervosa.
AB  - Visfatin is a recently described protein that is thought to regulate the process
      of adipocyte differentiation. Findings suggest that visfatin may be actively
      involved in the control of weight regulatory networks. However, to what extent
      and which role it plays in eating disorders is still poorly understood, as mixed
      results have been reported. The aim of the current study was to investigate serum
      visfatin concentrations on a cross sectional sample between acute anorexia
      nervosa patients (n=44), weight recovered patients (n=13) and healthy controls
      (n=46) and a longitudinal sample of acute patients (n=57) during weight recovery
      at three different time-points. Results did not show significant differences in
      visfatin between the three groups; however, acute patients showed a higher
      visfatin/BMI-SDS ratio than controls and recovered patients. Longitudinal results
      revealed an increase of visfatin levels during therapy. Our results suggest that
      high ratios of visfatin/BMI-SDS could be a state marker in acute anorexia
      nervosa, displaying a compensatory mechanism of the individual to maintain normal
      visfatin levels under malnourished conditions. 

PMID- 25617619
TI  - Operation performance and granule characterization of upflow anaerobic sludge
      blanket (UASB) reactor treating wastewater with starch as the sole carbon source.
AB  - Long-term performance of a lab-scale UASB reactor treating starch wastewater was
      investigated under different hydraulic retention times (HRT). Successful start-up
      could be achieved after 15days' operation. The optimal HRT was 6h with organic
      loading rate (OLR) 4g COD/Ld at COD concentration 1000mg/L, attaining 81.1-98.7%
      total COD removal with methane production rate of 0.33L CH4/g CODremoved.
      Specific methane activity tests demonstrated that methane formation via H2-CO2
      and acetate were the principal degradation pathways. Vertical characterizations
      revealed that main reactions including starch hydrolysis, acidification and
      methanogenesis occurred at the lower part of reactor ("main reaction zone");
      comparatively, at the up converting acetate into methane predominated ("substrate
      shortage zone"). Further reducing HRT to 3h caused volatile fatty acids
      accumulation, sludge floating and performance deterioration. Sludge floating was
      ascribed to the excess polysaccharides in extracellular polymeric substances
      (EPS). More efforts are required to overcome sludge floating-related issues. 

PMID- 25617620
TI  - Role of neuronal NADPH oxidase 1 in the peri-infarct regions after stroke.
AB  - The molecular mechanism underlying the selective vulnerability of neurons to
      oxidative damage caused by ischemia-reperfusion (I/R) injury remains unknown. We
      sought to determine the role of NADPH oxidase 1 (Nox1) in cerebral I/R-induced
      brain injury and survival of newborn cells in the ischemic injured region. Male
      Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO)
      followed by reperfusion. After reperfusion, infarction size, level of superoxide
      and 8-hydroxy-2'-deoxyguanosine (8-oxo-2dG), and Nox1 immunoreactivity were
      determined. RNAi-mediated knockdown of Nox1 was used to investigate the role of
      Nox1 in I/R-induced oxidative damage, neuronal death, motor function recovery,
      and ischemic neurogenesis. After I/R, Nox1 expression and 8-oxo-2dG
      immunoreactivity was increased in cortical neurons of the peri-infarct regions.
      Both infarction size and neuronal death in I/R injury were significantly reduced
      by adeno-associated virus (AAV)-mediated transduction of Nox1 short hairpin RNA
      (shRNA). AAV-mediated Nox1 knockdown enhanced functional recovery after MCAO. The
      level of survival and differentiation of newborn cells in the peri-infarct
      regions were increased by Nox1 inhibition. Our data suggest that Nox-1 may be
      responsible for oxidative damage to DNA, subsequent cortical neuronal
      degeneration, functional recovery, and regulation of ischemic neurogenesis in the
      peri-infarct regions after stroke. 

PMID- 25617621
TI  - The role of Latin America's land and water resources for global food security:
      environmental trade-offs of future food production pathways.
AB  - One of humanity's major challenges of the 21st century will be meeting future
      food demands on an increasingly resource constrained-planet. Global food
      production will have to rise by 70 percent between 2000 and 2050 to meet
      effective demand which poses major challenges to food production systems. Doing
      so without compromising environmental integrity is an even greater challenge.
      This study looks at the interdependencies between land and water resources,
      agricultural production and environmental outcomes in Latin America and the
      Caribbean (LAC), an area of growing importance in international agricultural
      markets. Special emphasis is given to the role of LAC's agriculture for (a)
      global food security and (b) environmental sustainability. We use the
      International Model for Policy Analysis of Agricultural Commodities and Trade
      (IMPACT)-a global dynamic partial equilibrium model of the agricultural sector-to
      run different future production scenarios, and agricultural trade regimes out to
      2050, and assess changes in related environmental indicators. Results indicate
      that further trade liberalization is crucial for improving food security
      globally, but that it would also lead to more environmental pressures in some
      regions across Latin America. Contrasting land expansion versus more intensified
      agriculture shows that productivity improvements are generally superior to
      agricultural land expansion, from an economic and environmental point of view.
      Finally, our analysis shows that there are trade-offs between environmental and
      food security goals for all agricultural development paths. 

PMID- 25617622
TI  - RNA-Seq reveals a role for NFAT-signaling in human retinal microvascular
      endothelial cells treated with TNFalpha.
AB  - TNFalpha has been identified as playing an important role in pathologic
      complications associated with diabetic retinopathy and retinal inflammation, such
      as retinal leukostasis. However, the transcriptional effects of TNFalpha on
      retinal microvascular endothelial cells and the different signaling pathways
      involved are not yet fully understood. In the present study, RNA-seq was used to
      profile the transcriptome of human retinal microvascular endothelial cells
      (HRMEC) treated for 4 hours with TNFalpha in the presence or absence of the NFAT
      specific inhibitor INCA-6, in order to gain insight into the specific effects of
      TNFalpha on RMEC and identify any involvement of NFAT signaling. Differential
      expression analysis revealed that TNFalpha treatment significantly upregulated
      the expression of 579 genes when compared to vehicle-treated controls, and
      subsequent pathway analysis revealed a TNFalpha-induced enrichment of transcripts
      associated with cytokine-cytokine receptor interactions, cell adhesion molecules,
      and leukocyte transendothelial migration. Differential expression analysis
      comparing TNFalpha-treated cells to those co-treated with INCA-6 revealed 10
      genes whose expression was significantly reduced by the NFAT inhibitor, including
      those encoding the proteins VCAM1 and CX3CL1 and cytokines CXCL10 and CXCL11.
      This study identifies the transcriptional effects of TNFalpha on HRMEC,
      highlighting its involvement in multiple pathways that contribute to retinal
      leukostasis, and identifying a previously unknown role for NFAT-signaling
      downstream of TNFalpha. 

PMID- 25617623
TI  - Aberrant gene expression in humans.
AB  - Gene expression as an intermediate molecular phenotype has been a focus of
      research interest. In particular, studies of expression quantitative trait loci
      (eQTL) have offered promise for understanding gene regulation through the
      discovery of genetic variants that explain variation in gene expression levels.
      Existing eQTL methods are designed for assessing the effects of common variants,
      but not rare variants. Here, we address the problem by establishing a novel
      analytical framework for evaluating the effects of rare or private variants on
      gene expression. Our method starts from the identification of outlier individuals
      that show markedly different gene expression from the majority of a population,
      and then reveals the contributions of private SNPs to the aberrant gene
      expression in these outliers. Using population-scale mRNA sequencing data, we
      identify outlier individuals using a multivariate approach. We find that outlier
      individuals are more readily detected with respect to gene sets that include
      genes involved in cellular regulation and signal transduction, and less likely to
      be detected with respect to the gene sets with genes involved in metabolic
      pathways and other fundamental molecular functions. Analysis of polymorphic data
      suggests that private SNPs of outlier individuals are enriched in the enhancer
      and promoter regions of corresponding aberrantly-expressed genes, suggesting a
      specific regulatory role of private SNPs, while the commonly-occurring regulatory
      genetic variants (i.e., eQTL SNPs) show little evidence of involvement.
      Additional data suggest that non-genetic factors may also underlie aberrant gene
      expression. Taken together, our findings advance a novel viewpoint relevant to
      situations wherein common eQTLs fail to predict gene expression when heritable,
      rare inter-individual variation exists. The analytical framework we describe,
      taking into consideration the reality of differential phenotypic robustness, may
      be valuable for investigating complex traits and conditions. 

PMID- 25617624
TI  - Endocardial tip cells in the human embryo - facts and hypotheses.
AB  - Experimental studies regarding coronary embryogenesis suggest that the
      endocardium is a source of endothelial cells for the myocardial networks. As this
      was not previously documented in human embryos, we aimed to study whether or not
      endothelial tip cells could be correlated with endocardial-dependent mechanisms
      of sprouting angiogenesis. Six human embryos (43-56 days) were obtained and
      processed in accordance with ethical regulations; immunohistochemistry was
      performed for CD105 (endoglin), CD31, CD34, alpha-smooth muscle actin, desmin and
      vimentin antibodies. Primitive main vessels were found deriving from both the
      sinus venosus and aorta, and were sought to be the primordia of the venous and
      arterial ends of cardiac microcirculation. Subepicardial vessels were found
      branching into the outer ventricular myocardium, with a pattern of recruiting
      alpha-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial
      sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within
      the inner myocardium, we found endothelial networks rooted from endocardium,
      guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip
      cells. The myocardial microcirculatory bed in the atria was mostly originated
      from endocardium, as well. Nevertheless, endocardial tip cells were also found in
      cardiac cushions, but they were not related to cushion endothelial networks. A
      general anatomical pattern of cardiac microvascular embryogenesis was thus
      hypothesized; the arterial and venous ends being linked, respectively, to the
      aorta and sinus venosus. Further elongation of the vessels may be related to the
      epicardium and subepicardial stroma and the intramyocardial network, depending on
      either endothelial and endocardial filopodia-guided tip cells in ventricles, or
      mostly on endocardium, in atria. 

PMID- 25617625
TI  - Improved inflammatory balance of human skeletal muscle during exercise after
      supplementations of the ginseng-based steroid Rg1.
AB  - The purpose of the study was to determine the effect of ginseng-based steroid Rg1
      on TNF-alpha and IL-10 gene expression in human skeletal muscle against exercise
      challenge, as well as on its ergogenic outcomes. Randomized double-blind placebo
      controlled crossover trials were performed, separated by a 4-week washout.
      Healthy young men were randomized into two groups and received capsule containing
      either 5 mg of Rg1 or Placebo one night and one hour before exercise. Muscle
      biopsies were conducted at baseline, immediately and 3 h after a standardized 60
      min cycle ergometer exercise. While treatment differences in glycogen depletion
      rate of biopsied quadriceps muscle during exercise did not reach statistical
      significance, Rg1 supplementations enhanced post-exercise glycogen replenishment
      and increased citrate synthase activity in the skeletal muscle 3 h after
      exercise, concurrent with improved meal tolerance during recovery (P<0.05). Rg1
      suppressed the exercise-induced increases in thiobarbituric acids reactive
      substance (TBARS) and reversed the increased TNF-alpha and decreased IL-10 mRNA
      of quadriceps muscle against the exercise challenge. PGC-1 alpha and GLUT4 mRNAs
      of exercised muscle were not affected by Rg1. Maximal aerobic capacity (VO2max)
      was not changed by Rg1. However, cycling time to exhaustion at 80% VO2max
      increased significantly by ~20% (P<0.05). CONCLUSION: Our result suggests that
      Rg1 is an ergogenic component of ginseng, which can minimize unwanted lipid
      peroxidation of exercised human skeletal muscle, and attenuate pro-inflammatory
      shift under exercise challenge.

PMID- 25617626
TI  - JAK2 exon 14 skipping in patients with primary myelofibrosis: a minor splice
      variant modulated by the JAK2-V617F allele burden.
AB  - BACKGROUND: Primary myelofibrosis (PMF) is an acquired clonal disease of the
      hematopoietic stem cell compartment, characterized by bone marrow fibrosis,
      anemia, splenomegaly and extramedullary hematopoiesis. About 60% of patients with
      PMF harbor a somatic mutation of the JAK2 gene (JAK2-V617F) in their
      hematopoietic lineage. Recently, a splicing isoform of JAK2, lacking exon 14
      (JAK2Delta14) was described in patients affected by myeloproliferative diseases.
      MATERIALS AND METHODS: By using a specific RT-qPCR method, we measured the ratio
      between the splicing isoform and the JAK2 full-length transcript (JAK2+14) in
      granulocytes, isolated from peripheral blood, of forty-four patients with PMF and
      nine healthy donors. RESULTS: We found that JAK2Delta14 was only slightly
      increased in patients and, at variance with published data, the splicing isoform
      was also detectable in healthy controls. We also found that, in patients bearing
      the JAK2-V617F mutation, the percentage of mutated alleles correlated with the
      observed increase in JAK2Delta14. Homozygosity for the mutation was also
      associated with a higher level of JAK2+14. Bioinformatic analysis indicates the
      possibility that the G>T transversion may interfere with the correct splicing of
      exon 14 by modifying a splicing regulatory sequence. CONCLUSIONS: Increased
      levels of JAK2 full-length transcript and a small but significant increase in
      JAK2 exon 14 skipping, are associated with the JAK2-V617F allele burden in PMF
      granulocytes. Our data do not confirm a previous claim that the production of the
      JAK2Delta14 isoform is related to the pathogenesis of PMF.

PMID- 25617627
TI  - Baicalein inhibits progression of gallbladder cancer cells by downregulating ZFX.
AB  - Baicalein, a widely used Chinese herbal medicine, has multiple pharmacological
      activities. However, the precise mechanisms of the anti-proliferation and anti
      metastatic effects of baicalein on gallbladder cancer (GBC) remain poorly
      understood. Therefore, the aim of this study was to assess the anti-proliferation
      and anti-metastatic effects of baicalein and the related mechanism(s) on GBC. In
      the present study, we found that treatment with baicalein induced a significant
      inhibitory effect on proliferation and promoted apoptosis in GBC-SD and SGC996
      cells, two widely used gallbladder cancer cell lines. Additionally, treatment
      with baicalein inhibited the metastasis of GBC cells. Moreover, we demonstrated
      for the first time that baicalein inhibited GBC cell growth and metastasis via
      down-regulation of the expression level of Zinc finger protein X-linked (ZFX). In
      conclusion, our studies suggest that baicalein may be a potential phytochemical
      flavonoid for therapeutics of GBC and ZFX may serve as a molecular marker or
      predictive target for GBC. 

PMID- 25617628
TI  - A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs
      immune response and reverses chronic cardiomyopathy.
AB  - Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical
      neglected tropical disease. Specific immunity promotes acute phase survival.
      Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy
      (CCC) associated with parasite persistence and immunological unbalance.
      Currently, the therapeutic management of patients only mitigates CCC symptoms.
      Therefore, a vaccine arises as an alternative to stimulate protective immunity
      and thereby prevent, delay progression and even reverse CCC. We examined this
      hypothesis by vaccinating mice with replication-defective human Type 5
      recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2
      (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic
      vaccination, naive C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using
      a homologous prime/boost protocol before challenge with the Colombian strain. For
      therapeutic vaccination, rAdVax administration was initiated at 120 days post
      infection (dpi), when mice were afflicted by CCC. Mice were analyzed for
      electrical abnormalities, immune response and cardiac parasitism and tissue
      damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb
      restricted cytotoxic and interferon (IFN)gamma-producing CD8+ T-cells, reduced
      acute heart parasitism and electrical abnormalities in the chronic phase.
      Therapeutic vaccination increased survival and reduced electrical abnormalities
      after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230
      dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities
      compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific
      IFNgamma-mediated immunity but reduced the response to polyclonal stimuli (anti
      CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO)
      levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as
      reduced the number of perforin+ cells, preserved the number of IFNgamma+ cells,
      increased the expression of IFNgamma mRNA but reduced inducible NO synthase mRNA.
      Vaccine-based immunostimulation with rAd might offer a rational alternative for
      re-programming the immune response to preserve and, moreover, recover tissue
      injury in Chagas' heart disease. 

PMID- 25617629
TI  - Validity of the age-adjusted charlson comorbidity index on clinical outcomes for
      patients with nasopharyngeal cancer post radiation treatment: a 5-year nationwide
      cohort study.
AB  - PURPOSE: To characterize the impact of comorbidity on survival outcomes for
      patients with nasopharyngeal carcinoma (NPC) post radiotherapy (RT). METHODS: A
      total of 4095 patients with NPC treated by RT or RT plus chemotherapy (CT) in the
      period from 2007 to 2011 were included through Taiwan's National Health Insurance
      Research Database. Information on comorbidity present prior to the NPC diagnosis
      was obtained and adapted to the Charlson Comorbidity Index (CCI), Age-Adjusted
      Charlson Comorbidity Index (ACCI) and a revised head and neck comorbidity index
      (HN-CCI). The prevalence of comorbidity and the influence on survival were
      calculated and analyzed. RESULTS: Most of the patients (75%) were male (age 51+/
      13 years) and 2470 of them (60%) had at least one comorbid condition. The most
      common comorbid condition was diabetes mellitus. According to these three
      different comorbidity index (CCI, ACCI and HN-CCI), higher scores were associated
      with worse overall survival (P< 0.001). The Receiver Operating Characteristic
      (ROC) curve was used to assess the discriminating ability of CCI, AACI and HN-CCI
      scores and it demonstrated the predictive ability for mortality with the ACCI
      (0.693, 95% CI 0.670-0.715) was superior to that of the CCI (0.619, 95% CI 0.593
      0.644) and HN-CCI (0.545, 95%CI 0.519-0.570). CONCLUSION: Comorbidities greatly
      influenced the clinical presentations, therapeutic interventions, and outcomes of
      patients with NPC post RT. Higher comorbidity index scores accurately was
      associated with worse survival. The ACCI seems to be a more appropriate
      prognostic indicator and should be considered in further clinical studies.

PMID- 25617630
TI  - Differential adipose tissue gene expression profiles in abacavir treated patients
      that may contribute to the understanding of cardiovascular risk: a microarray
      study.
AB  - OBJECTIVE: To compare changes in gene expression by microarray from subcutaneous
      adipose tissue from HIV treatment naive patients treated with efavirenz based
      regimens containing abacavir (ABC), tenofovir (TDF) or zidovidine (AZT). DESIGN:
      Subcutaneous fat biopsies were obtained before, at 6- and 18-24-months after
      treatment, and from HIV negative controls. Groups were age, ethnicity, weight,
      biochemical profile, and pre-treatment CD4 count matched. Microarray data was
      generated using the Agilent Whole Human Genome Microarray. Identification of
      differentially expressed genes and genomic response pathways was performed using
      limma and gene set enrichment analysis. RESULTS: There were significant
      divergences between ABC and the other two groups 6 months after treatment in
      genes controlling cell adhesion and environmental information processing, with
      some convergence at 18-24 months. Compared to controls the ABC group, but not AZT
      or TDF showed enrichment of genes controlling adherence junction, at 6 months and
      18-24 months (adjusted p<0.05) and focal adhesions and tight junction at 6 months
      (p<0.5). Genes controlling leukocyte transendothelial migration (p<0.05) and ECM
      receptor interactions (p = 0.04) were over-expressed in ABC compared to TDF and
      AZT at 6 months but not at 18-24 months. Enrichment of pathways and individual
      genes controlling cell adhesion and environmental information processing were
      specifically dysregulated in the ABC group in comparison with other treatments.
      There was little difference between AZT and TDF. CONCLUSION: After initiating
      treatment, there is divergence in the expression of genes controlling cell
      adhesion and environmental information processing between ABC and both TDF and
      AZT in subcutaneous adipose tissue. If similar changes are also taking place in
      other tissues including the coronary vasculature they may contribute to the
      increased risk of cardiovascular events reported in patients recently started on
      abacavir-containing regimens.

PMID- 25617633
TI  - Low-cost home-use light-emitting-diode phototherapy as an alternative to
      conventional methods.
AB  - BACKGROUND: The aim of our study was to evaluate whether a portable, light
      weight, light-emitting-diode phototherapy unit designed for home use is as
      effective as conventional blue-light fluorescent phototherapy (CFP) for treating
      hyperbilirubinemia in neonates. METHODS: A total of 50 patients were recruited
      sequentially for treatment using CFP (n = 25) and the home-type phototherapy unit
      (n = 25). RESULTS: The average rate of decrease in bilirubin levels was 0.17 +/-
      0.02 and 0.20 +/- 0.01 mg/dL/hours at the end of 24 hours in the groups receiving
      phototherapy by CFP and home-type phototherapy units, respectively. There was no
      statistically significant difference in the rate of the decrease in bilirubin
      levels between the groups (p = 0.104). CONCLUSIONS: It has been shown that the
      home-type phototherapy unit is as effective as CFP units in the treatment of
      neonatal hyperbilirubinemia and has the potential to become a standard of care
      for treatment of jaundiced neonates.

PMID- 25617631
TI  - Two novel alpha7 nicotinic acetylcholine receptor ligands: in vitro properties
      and their efficacy in collagen-induced arthritis in mice.
AB  - INTRODUCTION: The cholinergic anti-inflammatory pathway can downregulate
      inflammation via the release of acetylcholine (ACh) by the vagus nerve. This
      neurotransmitter binds to the alpha7 subunit of nicotinic acetylcholine receptors
      (alpha7nAChR), expressed on macrophages and other immune cells. We tested the
      pharmacological and functional profile of two novel compounds, PMP-311 and PMP
      072 and investigated their role in modulating collagen-induced arthritis (CIA) in
      mice. METHODS: Both compounds were characterized with binding,
      electrophysiological, and pharmacokinetic studies. For in vivo efficacy studies
      in the CIA model the compounds were administered daily by oral gavage from day 20
      till sacrifice at day 34. Disease progression was monitored by visual clinical
      scoring and measurement of paw swelling. Inflammation and joint destruction were
      examined by histology and radiology. RESULTS: Treatment with PMP-311 was
      effective in preventing disease onset, reducing clinical signs of arthritis, and
      reducing synovial inflammation and bone destruction. PMP-072 also showed a trend
      in arthritis reduction at all concentrations tested. The data showed that while
      both compounds bind to alpha7nAChR with high affinity, PMP-311 acts like a
      classical agonist of ion channel activity, and PMP-072 can actually act as an ion
      channel antagonist. Moreover, PMP-072 was clearly distinct from typical
      competitive antagonists, since it was able to act as a silent agonist. It
      synergizes with the allosteric modulator PNU-120596, and subsequently activates
      desensitized alpha7nAChR. However, PMP-072 was less efficacious than PMP-311 at
      both channel activation and desensitization, suggesting that both conducting and
      non-conducting states maybe of importance in driving an anti-inflammatory
      response. Finally, we found that the anti-arthritic effect can be observed
      despite limited penetration of the central nervous system. CONCLUSIONS: These
      data provide direct evidence that the alpha7nAChR in immune cells does not
      require typical ion channel activation to exert its antiinflammatory effects.

PMID- 25617634
TI  - Patterns of coping strategy use and relationships with psychosocial health in
      adolescents with spinal cord injury.
AB  - OBJECTIVE: To investigate patterns of coping among adolescents with spinal cord
      injury (SCI). METHODS: Youth aged 13-18 years with SCI completed measures of
      participation, quality of life (QOL), mental health symptoms, and coping. A
      hierarchical agglomerative cluster analysis using Ward's method was conducted.
      Subsequent analyses examined relationships between clusters and psychosocial
      functioning. RESULTS: 199 youth were an average of 15.95 years (SD = 1.71) at
      interview and 11.02 years (SD = 5.45) at injury. 56% percent were male, 64%
      White, and 62% had paraplegia. Four groups of "copers" emerged: ineffective,
      active, avoidant, and cognitive. Cognitive copers reported significantly less
      mental health symptomatology and higher QOL, followed by avoidant, active, and
      ineffective copers. Active copers showed significantly greater participation
      relative to ineffective, avoidant, and cognitive copers. CONCLUSIONS: These
      results suggest that coping profiles have meaningful relationships with
      adjustment. Reliance on cognitive strategies, with low endorsement of other
      strategies, may be associated with better psychosocial health.

PMID- 25617632
TI  - Probing conformational stability and dynamics of erythroid and nonerythroid
      spectrin: effects of urea and guanidine hydrochloride.
AB  - We have studied the conformational stability of the two homologous membrane
      skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric
      and tetrameric forms respectively during unfolding in the presence of urea and
      guanidine hydrochloride (GuHCl). Fluorescence and circular dichroism (CD)
      spectroscopy have been used to study the changes of intrinsic tryptophan
      fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1
      anilinonapthalene-8-sulfonic acid (ANS). Chemical unfolding of both proteins were
      reversible and could be described as a two state transition. The folded erythroid
      spectrin and non-erythroid spectrin were directly converted to unfolded monomer
      without formation of any intermediate. Fluorescence quenching, anisotropy, ANS
      binding and dynamic light scattering data suggest that in presence of low
      concentrations of the denaturants (up-to 1M) hydrogen bonding network and van der
      Waals interaction play a role inducing changes in quaternary as well as tertiary
      structures without complete dissociation of the subunits. This is the first
      report of two large worm like, multi-domain proteins obeying twofold rule which
      is commonly found in small globular proteins. The free energy of stabilization
      (DeltaGuH20) for the dimeric spectrin has been 20 kcal/mol lesser than the
      tetrameric from. 

PMID- 25617635
TI  - Exploring the utility of phylogenetic analysis of cytochrome oxidase gene subunit
      I as a complementary tool to classical taxonomical identification of phlebotomine
      sand fly species (Diptera, Psychodidae) from southern Europe.
AB  - Phlebotomine sand flies (Diptera, Psychodidae) are known to be vectors of several
      pathogens such as Leishmania and Phlebovirus genera. The identification of
      phlebotomine sand fly species is currently based on morphological characters, and
      requires considerable taxonomic expertise and skilfulness, but may be
      complemented by DNA-based analyses for (i) accurate species identification and
      (ii) for estimating sand fly diversity. The aim of this study was to evaluate the
      utility of mitochondrial cytochrome oxidase gene subunit I (cox1) sequence
      analysis as a complementary tool to classical taxonomical for the identification
      of the most prevalent phlebotomine sand fly species from southern Europe (i.e.
      Phlebotomus ariasi, P. perniciosus, P. sergenti and Sergentomyia minuta).
      Phylogenetic analyses of cox1 sequences allowed conclusive assignment of most of
      the sand flies into individual species, and revealed the genetic heterogeneity
      that characterizes some of the identified genetic clusters. Nevertheless, it
      showed some limitations, as it failed to (i) allocate correctly all of all
      species of a given subgenus to a single lineage, or (ii) conclusively identify
      sequences amplified from individuals classified morphologically as P. ariasi. A
      more extensive analysis of cox1 sequences together with morphometric
      characterization of specimens from different geographic areas/regions might be
      useful for the correct assessment of the phylogenetic relationship within the P.
      ariasi/P. chadlii cluster and/or help to ascertain the usefulness of cox1 for
      molecular taxonomy of sand flies.

PMID- 25617637
TI  - [In Process Citation].

PMID- 25617636
TI  - Occurrence of a mosquito vector in bird houses: Developmental consequences and
      potential epidemiological implications.
AB  - Even with continuous vector control, dengue is still a growing threat to public
      health in Southeast Asia. Main causes comprise difficulties in identifying
      productive breeding sites and inappropriate targeted chemical interventions. In
      this region, rural families keep live birds in backyards and dengue mosquitoes
      have been reported in containers in the cages. To focus on this particular
      breeding site, we examined the capacity of bird fecal matter (BFM) from the
      spotted dove, to support Aedes albopictus larval growth. The impact of BFM larval
      uptake on some adult fitness traits influencing vectorial capacity was also
      investigated. In serial bioassays involving a high and low larval density (HD and
      LD), BFM and larval standard food (LSF) affected differently larval development.
      At HD, development was longer in the BFM environment. There were no appreciable
      mortality differences between the two treatments, which resulted in similar
      pupation and adult emergence successes. BFM treatment produced a better gender
      balance. There were comparable levels of blood uptake and egg production in BFM
      and LSF females at LD; that was not the case for the HD one, which resulted in
      bigger adults. BFM and LSF females displayed equivalent lifespans; in males, this
      parameter was shorter in those derived from the BFM/LD treatment. Taken together
      these results suggest that bird defecations successfully support the development
      of Ae. albopictus. Due to their cryptic aspects, containers used to supply water
      to encaged birds may not have been targeted by chemical interventions.

PMID- 25617638
TI  - [Perioperative blood glucose levels and surgical site infections in patients
      undergoing colorectal cancer surgery: a feasibility study].
AB  - This study was carried out in the framework of a regional surveillance program of
      surgical site infections, to assess the feasibility of performing a longitudinal
      study to evaluate possible correlations between perioperative blood glucose
      levels and surgical site infections in patients undergoing colorectal cancer
      surgery. A convenience sample of patients aged 18 years and above, admitted to
      the University Hospital of Udine (Friuli Venezia Giulia region, Italy) from 1
      January to 31 March 2011, were invited to participate in the study. Patients
      admitted for recanalization surgery for obstructing carcinomas were excluded.
      Twenty-five patients participated in the study, 20% (n=5) of whom had a surgical
      site infection. No correlation was found between blood glucose levels and
      surgical site infections. The costs of performing a study of this kind would be
      mainly related to the number of persons involved in data collection and the
      estimated time required is 12 to 18 months. For the future conduct of the study,
      it is hoped that simpler operational methods may be agreed upon within the
      healthcare facility. 

PMID- 25617639
TI  - [Health risks associated with urban environmental pollution in Europe: results of
      the HEREPLUS multicentre study in Rome (Italy)].
AB  - Urban air pollution is known to cause numerous health problems. The HEREPLUS
      project aims to evaluate the association between environmental air pollution and
      health and to provide guidelines for the management and organization of the urban
      environment. Risk maps were developed by georeferentiation, using hospitalization
      data and concentration levels of ozone and pollution matter. Data for four
      European cities involved in the project (Rome, Madrid, Dresden, and Athens) were
      analysed for the period 2003-2004. In this article, we report results for Rome
      only. Study findings demonstrated that the green area in a city reduces pollution
      in a city reduces pollution levels in the atmosphere, thus reducing health risks.

PMID- 25617640
TI  - [The "Smoke-free hospital" project: prevalence of smokers in a large hospital in
      Pavia (Italy) from 2006 to 2010].
AB  - This study was conducted in the context of the "Smoke-free Hospital" project and
      its aims were to describe the prevalence of smokers among employees and patients
      of the Hospital of Pavia from 2006 to 2010, and to evaluate its determinants. The
      target population was represented by all employees (healthcare and other staff)
      and patients (inpatients and outpatients) of the Hospital of Pavia. Data
      collection took place by means of two self-administered and anonymous
      questionnaires (one for employees and one for patients). Overall, 3,996 employees
      and 2,301 patients completed the questionnaires. The prevalence of smokers among
      participating individuals remained largely unchanged in the observed period. The
      percentage of smokers among employees ranged from 21.88% in 2007 to 23% in 2006,
      while among patients it ranged from 16.67% in 2006 to 24.05% in 2008. Knowledge
      about tobacco-related issues was found to be poor and did not change over time.
      The low response rate did not allow us to generalize results to the entire target
      population. However, results indicate the need for health promotion campaigns
      both among hospital employees and among the general population, to raise
      awareness regarding the risks of tobacco smoking and to reduce the prevalence of
      smokers. 

PMID- 25617641
TI  - Parents' awareness and acceptance of HPV vaccination in Italy.
AB  - The aims of this study were to evaluate parents' awareness about HPV infection
      and vaccination and to identify reasons for not accepting vaccination and the
      type of health professionals involved in information campaigns. The study
      involved three schools. Overall, 1200 questionnaires were distributed to parents
      of female students born between 1993 and 2000 (age 12 to 19 years at the time of
      the study). The majority of students accepted to be vaccinated. Parents received
      information from different sources. 

PMID- 25617642
TI  - [The post-mortem external examination in Italy: critical issues and
      perspectives].
AB  - The purpose of the postmortem external examination is to ascertain death and
      authorize burial. Requirements regarding external postmortem examinations and the
      tasks of physicians having this specific duty, vary in different regions of
      Italy. In this study, we analyzed the rationale and role of physicians performing
      post mortem external examinations. The role of physicians ascertaining death
      should be enhanced and they should play a bigger role in the identification and
      verification of the cause of death. A reorganization of post-mortem procedures
      also appears necessary. 

PMID- 25617643
TI  - [Features and developments of Primary Care in a Public Health perspective].
AB  - In recent years, substantial changes of the population structure have occurred,
      both at the national and international levels, due to several factors, including
      demographic changes and technological progress. At the same time, an
      epidemiological transition is occurring, characterized by a shift from diseases
      with an acute onset and a rapid resolution, to chronic-degenerative conditions
      which require more long-term care solutions. This shift seems to contribute to an
      increased life expectancy of the population, and a larger proportion of elderly
      individuals having complex health needs. The above described changes of the
      population structure, in combination with the current economic and financial
      crisis, require a redefinition of health system priorities at different levels,
      and the identification of specific intervention approaches. Today Primary Care is
      generally considered to have a key role in the progress of health systems and
      governments and international agencies, including the World Bank and the World
      Health Organisation have already increased investments and introduced reforms of
      Primary Care. However, there still remains much to be done, particularly with
      regards to the definition of specific aspects related to Primary Care. In this
      article the characteristics and developments of two main concepts, Primary Care
      (PC), which describes the delivery of Primary Care services, and Primary Health
      Care (PHC), which is more broadly defined by a level of governance or
      stewardship, are described. The distinction between PC and PHC implies the need
      for a characterization of system governance or stewardship, and of governance for
      care delivery. The first entails decision-making mechanisms for protecting the
      health both of individuals and of communities, by setting health, appropriateness
      and economic sustainability goals. These decisionmaking mechanisms further take
      into account the consequent responsibilities and risks compared to the achieved
      results toward citizens. The second relates to decision-making mechanisms for the
      delivery of services. Some examples are given of the application of system
      governance for primary healthcare at the national level and of characteristics of
      aggregations of professionals and/or structures for PC delivery. Finally, ideas
      and proposals for the development of an integrated approach for the delivery of
      Primary Care and prevention services, in a Public Health perspective are
      presented. 

PMID- 25617644
TI  - [Communicating the benefits and risks of vaccination: a focus on the PFCC
      (Patient and Family Centered Care) approach].
AB  - In recent years an important reduction in the access to vaccination was noticed
      in Italy. Health care workers involved in health promotion must necessarily find
      new strategies to overcome the mistrust of the population. The application of
      some instruments of counselling in the vaccination field can improve the
      therapeutic alliance, making users to take the best decisions for their own
      wellness. The approach called Patient- and Family-Centered Care includes the
      relational processes within the skills of the health care worker. 

PMID- 25617645
TI  - Computation in dynamically bounded asymmetric systems.
AB  - Previous explanations of computations performed by recurrent networks have
      focused on symmetrically connected saturating neurons and their convergence
      toward attractors. Here we analyze the behavior of asymmetrical connected
      networks of linear threshold neurons, whose positive response is unbounded. We
      show that, for a wide range of parameters, this asymmetry brings interesting and
      computationally useful dynamical properties. When driven by input, the network
      explores potential solutions through highly unstable 'expansion' dynamics. This
      expansion is steered and constrained by negative divergence of the dynamics,
      which ensures that the dimensionality of the solution space continues to reduce
      until an acceptable solution manifold is reached. Then the system contracts
      stably on this manifold towards its final solution trajectory. The unstable
      positive feedback and cross inhibition that underlie expansion and divergence are
      common motifs in molecular and neuronal networks. Therefore we propose that very
      simple organizational constraints that combine these motifs can lead to
      spontaneous computation and so to the spontaneous modification of entropy that is
      characteristic of living systems. 

PMID- 25617646
TI  - Commentary: Vitamin A policies need rethinking.

PMID- 25617647
TI  - Cohort Profile: FAMILY Cohort.
AB  - The FAMILY Cohort is a longitudinal study of health, happiness and family harmony
      (the '3Hs') at individual, household and neighbourhood levels in Hong Kong. Using
      a family living in the same household as the sampling unit, the study (n = 20 279
      households and 46 001 participants) consists of a composite sample from several
      sources, including: a population-representative random core sample (n = 8115
      households and 19 533 participants); the first-degree relatives of this sample (n
      = 4658 households and 11 063 participants); and oversampling in three new towns
      (n = 2891 households and 7645 participants) and in three population subgroups
      with anticipated changes in family dynamics (n = 909 households and 2160
      participants). Two household visits and five telephone- or web-based follow-ups
      were conducted over 2009-14. Data collected include socio-demographics,
      anthropometrics, lifestyle and behavioural factors, measures of social capital,
      and standardized instruments assessing the 3Hs. We also intend to collect
      biomaterials in future. The analytical plan includes multilevel inter-relations
      of the 3Hs for individuals, households, extended families and neighbourhoods.
      With Hong Kong's recent history of socioeconomic development, the FAMILY Cohort
      is therefore relevant to global urban populations currently experiencing
      similarly rapid economic growth. The FAMILY Cohort is currently set up as a
      supported access resource.

PMID- 25617648
TI  - Response to: J Mason et al. Vitamin A policies need rethinking.

PMID- 25617649
TI  - Commentary: Migrant study designs for epigenetic studies of disease risk.

PMID- 25617650
TI  - Could child vitamin A supplementation have long-term health effects?

PMID- 25617651
TI  - Post-spike hyperpolarization participates in the formation of auditory behavior
      related response patterns of inferior collicular neurons in Hipposideros pratti.
AB  - To probe the mechanism underlying the auditory behavior-related response patterns
      of inferior collicular neurons to constant frequency-frequency modulation (CF-FM)
      stimulus in Hipposideros pratti, we studied the role of post-spike
      hyperpolarization (PSH) in the formation of response patterns. Neurons obtained
      by in vivo extracellular (N=145) and intracellular (N=171) recordings could be
      consistently classified into single-on (SO) and double-on (DO) neurons. Using
      intracellular recording, we found that both SO and DO neurons have a PSH with
      different durations. Statistical analysis showed that most SO neurons had a
      longer PSH duration than DO neurons (p<0.01). These data suggested that the PSH
      directly participated in the formation of SO and DO neurons, and the PSH elicited
      by the CF component was the main synaptic mechanism underlying the SO and DO
      response patterns. The possible biological significance of these findings
      relevant to bat echolocation is discussed. 

PMID- 25617652
TI  - Effect of synthetic steroids on GABAA receptor binding in rat brain.
AB  - Neuroactive steroids, like allopregnanolone (A) and pregnanolone (P), bind to
      specifics sites on the GABAA receptor complex and modulate receptor function.
      They are capable to inhibit or stimulate the binding of GABAA receptor-specific
      ligands, like t-butyl-bicyclophosphorothionate, flunitrazepam and muscimol. We
      have previously characterized a set of oxygen-bridged synthetic steroids (SS)
      analogs to A or P using synaptosomes. Considering that the subunit composition of
      the GABAA receptor throughout the central nervous system affects the magnitude of
      the modulation of the GABAA receptor by NAS, we evaluated the action of two
      selected SS, in brain sections containing the cerebral cortex (CC) and
      hippocampus (HC) using quantitative receptor autoradiography. Both SS affected
      the binding of the three ligands in a similar way to A and P, with some
      differences on certain CC layers according to the ligand used. One of the SS, the
      3alpha-hydroxy-6,19-epoxypregn-4-ene-20-one (compound 5), behaved similarly to
      the natural neuroactive steroids. However, significant differences with compound
      5 were observed on the HC CA2 region, making it steroid suitable for a specific
      action. Those differences may be related to structural conformation of the SS and
      the subunits' composition present on the receptor complex. 

PMID- 25617653
TI  - Oxytocin-induced membrane hyperpolarization in pain-sensitive dorsal root ganglia
      neurons mediated by Ca(2+)/nNOS/NO/KATP pathway.
AB  - Oxytocin (OT) plays an important role in pain modulation and antinociception in
      the central nervous system. However, little is known about its peripheral
      effects. This study was conducted to investigate the effect of OT on the
      electrical properties of neurons in the dorsal root ganglia (DRG) and the
      underlying mechanisms. DRG neurons from adult rats were acutely dissociated and
      cultured. Intracellular Ca(2+) was determined by fluorescent microscopy using an
      indicator dye. The electrical properties of DRG neurons were tested by patch
      clamp recording. The oxytocin receptor (OTR) and neuronal nitric oxide synthase
      (nNOS) on DRG neurons were assessed with immunofluorescence assays. OTR co
      localized with nNOS in most of Isolectin B4 (IB4)-binding cultured DRG neurons in
      rats. OT decreased the excitability, increased the outward current, and evoked
      the membrane hyperpolarization in cultured DRG neurons. Sodium nitroprusside
      (SNP), the donor of nitric oxide (NO), exerted similar effects as OT on the
      membrane potential of cultured DRG neurons. OT increased the production of NO in
      DRGs and cultured DRG neurons. Pre-treatment of the OTR antagonist atosiban or
      the selective nNOS inhibitor N-Propyl-l-arginine (NPLA) significantly attenuated
      the hyperpolarization effect evoked by OT. OT produced a concentration-dependent
      increase in intracellular Ca(2+) in DRG neurons that responds to capsaicin, which
      can be attenuated by atosiban, but not by NPLA. OT-evoked membrane
      hyperpolarization and increase of outward current were distinctly attenuated by
      glibenclamide, a blocker of ATP-sensitive K(+) (KATP) channel. OT might be an
      endogenous antinociceptive agent and the peripheral antinociceptive effects of OT
      are mediated by activation of the Ca(2+)/nNOS/NO/KATP pathway in DRG neurons. 

PMID- 25617655
TI  - The effect of anodal transcranial direct current stimulation on multi-limb
      coordination performance.
AB  - Motor coordination is the combination of body movements performed in a well
      planned and controlled manner based upon motor commands from the brain. Several
      interventions have been in practice to improve motor control. Transcranial direct
      current stimulation (tDCS) is getting a lot of attention these days for its
      effect in improving motor functions. Studies focusing on the ability of tDCS to
      improve motor control, inhibition and coordination are sparse. Therefore, the
      influence of tDCS stimulation at the right dorsolateral prefrontal cortex (DLPFC)
      on motor control and coordination was investigated, in a sham-controlled double
      blinded pseudo-randomized design, with a multi-limb coordination task in healthy
      young subjects. Number of errors and reaction time were used as outcome
      parameters. Our findings showed that, anodal tDCS reduced the number of errors
      only in the heterolateral coordination condition, however there was no change in
      reaction time. No changes were found for the homolateral and three-limb
      coordination conditions. 

PMID- 25617656
TI  - Environmental stimulation improves performance in the ox-maze task and recovers
      Na+,K+-ATPase activity in the hippocampus of hypoxic-ischemic rats.
AB  - In animal models, environmental enrichment (EE) has been found to be an efficient
      treatment for alleviating the consequences of neonatal hypoxia-ischemia (HI).
      However the potential for this therapeutic strategy and the mechanisms involved
      are not yet clear. The aim of present study is to investigate behavioral
      performance in the ox-maze test and Na+,K+-ATPase, catalase (CAT) and glutathione
      peroxidase (GPx) activities in the hippocampus of rats that suffered neonatal HI
      and were stimulated in an enriched environment. Seven-day-old rats were submitted
      to the HI procedure and divided into four groups: control maintained in standard
      environment (CTSE), control submitted to EE (CTEE), HI in standard environment
      (HISE) and HI in EE (HIEE). Animals were stimulated with EE for 9 weeks (1 h/day
      for 6 days/week) and then behavioral and biochemical parameters were evaluated.
      Present results indicate learning and memory in the ox-maze task were impaired in
      HI rats and this effect was recovered after EE. Hypoxic-ischemic event did not
      alter the Na+,K+-ATPase activity in the right hippocampus (ipsilateral to
      arterial occlusion). However, on the contralateral hemisphere, HI caused a
      decrease in this enzyme activity that was recovered by EE. The activities of GPx
      and CAT were not changed by HI in any group evaluated. In conclusion, EE was
      effective in recovering learning and memory impairment in the ox-maze task and
      Na+,K+-ATPase activity in the hippocampus caused by HI. The present data provide
      further support for the therapeutic potential of environmental stimulation after
      neonatal HI in rats.

PMID- 25617654
TI  - Activity-dependent degeneration of axotomized neuromuscular synapses in Wld S
      mice.
AB  - Activity and disuse of synapses are thought to influence progression of several
      neurodegenerative diseases in which synaptic degeneration is an early sign. Here
      we tested whether stimulation or disuse renders neuromuscular synapses more or
      less vulnerable to degeneration, using axotomy as a robust trigger. We took
      advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular
      junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of
      Wallerian degeneration-Slow (Wld(S)) mutant mice. First, we maintained ex vivo
      FDB and DL nerve-muscle explants at 32 degrees C for up to 48 h. About 90% of
      fibers from Wld(S) mice remained innervated, compared with about 36% in wild-type
      muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100
      Hz: 1s/100s) reduced synaptic protection in Wld(S) preparations by about 50%.
      This effect was abolished in reduced Ca(2+) solutions. Next, we assayed FDB and
      DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve
      conduction in vivo, followed by tibial nerve axotomy. Five days later, only about
      9% of motor endplates remained innervated in the paralyzed muscles, compared with
      about 50% in 5 day-axotomized muscles from saline-control-treated Wld(S) mice
      with no conditioning nerve block. Finally, we gave mice access to running wheels
      for up to 4 weeks prior to axotomy. Surprisingly, exercising Wld(S) mice ad
      libitum for 4 weeks increased about twofold the amount of subsequent axotomy
      induced synaptic degeneration. Together, the data suggest that vulnerability of
      mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may
      be enhanced bimodally, either by disuse or by hyperactivity.

PMID- 25617657
TI  - Streptococcus agalactiae infection in zebrafish larvae.
AB  - Streptococcus agalactiae (Group B Streptococcus, GBS) is an encapsulated, Gram
      positive bacterium that is a leading cause of neonatal pneumonia, sepsis and
      meningitis, and an emerging aquaculture pathogen. The zebrafish (Danio rerio) is
      a genetically tractable model vertebrate that has been used to analyze the
      pathogenesis of both aquatic and human bacterial pathogens. We have developed a
      larval zebrafish model of GBS infection to study bacterial and host factors that
      contribute to disease progression. GBS infection resulted in dose dependent
      larval death, and GBS serotype III, ST-17 strain was observed as the most
      virulent. Virulence was dependent on the presence of the GBS capsule, surface
      anchored lipoteichoic acid (LTA) and toxin production, as infection with GBS
      mutants lacking these factors resulted in little to no mortality. Additionally,
      interleukin-1beta (il1b) and CXCL-8 (cxcl8a) were significantly induced following
      GBS infection compared to controls. We also visualized GBS outside the brain
      vasculature, suggesting GBS penetration into the brain during the course of
      infection. Our data demonstrate that zebrafish larvae are a valuable model
      organism to study GBS pathogenesis. 

PMID- 25617658
TI  - The heart of the story: peripheral physiology during narrative exposure predicts
      charitable giving.
AB  - Emotionally laden narratives are often used as persuasive appeals by charitable
      organizations. Physiological responses to a narrative may explain why some people
      respond to an appeal while others do not. In this study we tested whether
      autonomic and hormonal activity during a narrative predict subsequent narrative
      influence via charitable giving. Participants viewed a brief story of a father's
      experience with his 2-year-old son who has terminal cancer. After the story,
      participants were presented with an opportunity to donate some of their study
      earnings to a related charity. Measures derived from cardiac and electrodermal
      activity, including HF-HRV, significantly predicted donor status. Time-series
      GARCH models of physiology during the narrative further differentiated donors
      from non-donors. Moreover, cardiac activity and experienced concern were found to
      covary from moment-to-moment across the narrative. Our findings indicate that the
      physiological response to a stimulus, herein a narrative, can predict influence
      as indexed by stimulus-related behavior. 

PMID- 25617660
TI  - Structure-fluctuation-function relationships of seven pro-angiogenic isoforms of
      VEGFA, important mediators of tumorigenesis.
AB  - Vascular endothelial growth factor A (VEGFA) has different biological activities
      and plays a central role in tumor proliferation, angiogenesis and metastasis.
      Different VEGFA isoforms are generated by alternative splice site selection of
      exons 6, 7 and 8. In this paper, we analyzed the physical and chemical properties
      of the VEGFA exon 6 sequence, and modeled the three-dimensional structures of the
      regions corresponding to exons 6, 7 and 8 of six different pro-angiogenic
      isoforms of VEGFA in comparison to the experimental structure of VEGFA_165 by a
      combined approach of fold recognition and comparative modeling strategies and
      molecular dynamics simulations. Our results showed that i) exon 6 is a very
      flexible polycation with high disordered propensity, features well conserved in
      all mammals, ii) the structures of all the isoforms are stabilized by H-bond sub
      networks organized around HUB residues and, iii) the charge content of exon 6
      modulates the intrinsic structural preference of its flexible backbone, which can
      be described as an ensemble of conformations. Moreover, complexes between NRP-1
      and VEGFA isoforms were modeled by molecular docking to study what isoforms are
      able to bind NRP-1. The analysis of complexes evidenced that VEGFA_121,
      VEGFA_145, VEGFA_183, VEGFA_189 and VEGFA_206, containing exons 7 and 8a, are
      able to interact with NRP-1 because they have the key regions of exons 7b and/or
      8a. An overview of the isoforms shows how the fluctuations are the main guidance
      of their biological function. MD simulations also provide insights into factors
      that stabilize the binding regions of isoforms. 

PMID- 25617659
TI  - Mass spectrometry-based characterization of endogenous peptides and metabolites
      in small volume samples.
AB  - Technologies to assay single cells and their extracellular microenvironments are
      valuable in elucidating biological function, but there are challenges. Sample
      volumes are low, the physicochemical parameters of the analytes vary widely, and
      the cellular environment is chemically complex. In addition, the inherent
      difficulty of isolating individual cells and handling small volume samples
      complicates many experimental protocols. Here we highlight a number of mass
      spectrometry (MS)-based measurement approaches for characterizing the chemical
      content of small volume analytes, with a focus on methods used to detect
      intracellular and extracellular metabolites and peptides from samples as small as
      individual cells. MS has become one of the most effective means for analyzing
      small biological samples due to its high sensitivity, low analyte consumption,
      compatibility with a wide array of sampling approaches, and ability to detect a
      large number of analytes with different properties without preselection. Having
      access to a flexible portfolio of MS-based methods allows quantitative,
      qualitative, untargeted, targeted, multiplexed, and spatially resolved
      investigations of single cells and their similarly scaled extracellular
      environments. Combining MS with on-line and off-line sample conditioning tools,
      such as microfluidic and capillary electrophoresis systems, significantly
      increases the analytical coverage of the sample's metabolome and peptidome, and
      improves individual analyte characterization/identification. Small volume assays
      help to reveal the causes and manifestations of biological and pathological
      variability, as well as the functional heterogeneity of individual cells within
      their microenvironments and within cellular populations. This article is part of
      a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and
      Neurology. 

PMID- 25617662
TI  - Chronic kidney disease prevalence in Rivas, Nicaragua: use of a field device for
      creatinine measurement.
AB  - OBJECTIVE: An epidemic of chronic kidney disease (CKD) has been identified in
      Pacific coastal regions of Central America, and screening in the field in these
      low income countries remains logistically problematic. We tested the performance
      characteristics of a point of care creatinine analyzer compared to standardized
      serum creatinine measurements. METHODS: Measurements were conducted in 100
      persons from a local health center (n=34) and hospital (n=66) in Rivas, Nicaragua
      using both a point-of-care analyzer (StatSensor Xpress, Nova Biomedical) and
      serum creatinine by Jaffe kinetic method with a Roche Cobas Integra 400 analyzer.
      Percent coefficient of variation, sensitivity and specificity of the StatSensor
      Xpress were determined. RESULTS: The average coefficient of variation (CV) was
      1.28% for the serum creatinine and CV for the StatSensor Xpress analyzer was
      6.8%. The median intra-individual creatinine results obtained with the StatSensor
      Xpress device were 0.32 mg/dL higher than those by serum creatinine by Jaffe
      kinetic method. The sensitivity and specificity of the StatSensor Xpress device
      for identifying subjects with abnormal creatinine (defined as >1.2 mg/dL) was
      100% and 79%, respectively. CONCLUSIONS: Point of care testing for creatinine
      demonstrated acceptable repeatability, excellent sensitivity (100%) and modest
      specificity (79%). Using the point of care testing will allow for generalized
      screening in the field in low income countries; however, confirmation for
      elevated levels >1.2 mg/dL will require a second laboratory test confirmation.

PMID- 25617661
TI  - Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker
      discovery.
AB  - Identification of reliable and robust biomarkers is crucial to enable early
      diagnosis of Parkinson disease (PD) and monitoring disease progression. While
      imperfect, the slow, chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced non-human primate animal model system of parkinsonism is an abundant
      source of pre-motor or early stage PD biomarker discovery. Here, we present a
      study of a MPTP rhesus monkey model of PD that utilizes complementary
      quantitative iTRAQ-based proteomic, glycoproteomics and phosphoproteomics
      approaches. We compared the glycoprotein, non-glycoprotein, and phosphoprotein
      profiles in the putamen of asymptomatic and symptomatic MPTP-treated monkeys as
      well as saline injected controls. We identified 86 glycoproteins, 163 non
      glycoproteins, and 71 phosphoproteins differentially expressed in the MPTP
      treated groups. Functional analysis of the data sets inferred the biological
      processes and pathways that link to neurodegeneration in PD and related
      disorders. Several potential biomarkers identified in this study have already
      been translated for their usefulness in PD diagnosis in human subjects and
      further validation investigations are currently under way. In addition to
      providing potential early PD biomarkers, this comprehensive quantitative
      proteomic study may also shed insights regarding the mechanisms underlying early
      PD development. This article is part of a Special Issue entitled:
      Neuroproteomics: Applications in neuroscience and neurology. 

PMID- 25617663
TI  - Use and interpretation of high sensitivity cardiac troponins in patients with
      chronic kidney disease with and without acute myocardial infarction.
AB  - It is well known that the population with chronic kidney disease (CKD) is at
      greater risk for cardiovascular disease and death than the general population.
      The use and interpretation of high sensitivity cardiac troponin (hs-cTn) assays
      have been particularly challenging in these patients with the majority having
      elevated levels at baseline. The diagnostic accuracy of acute myocardial
      infarction (AMI) may be decreased in patients with CKD when using these newer
      troponins. In order to improve the sensitivity and specificity for the diagnosis
      of AMI, one must look at the change in cTn and consider using higher cut-off
      values. In asymptomatic patients with CKD, research has shown increased
      prevalence of cardiovascular risk factors and underlying structural heart disease
      with increasing cTn levels. Prognostically, elevated cTn has been associated with
      adverse outcomes including incident heart failure and cardiovascular mortality.
      The purpose of the review is to evaluate hs-cTn in patients with CKD for the
      diagnosis of AMI and for the prognostic significance of elevated levels in CKD
      patients without AMI. Although the underlying etiology of persistently elevated
      cTn in the CKD population remains unclear, the review will also evaluate studies
      attempting to explain whether the source of cTn is from increased cardiac
      production versus decreased renal clearance. Further longitudinal studies are
      required in order to bridge the gap between the prognostic importance of elevated
      cTn and clinical management to prevent symptomatic cardiac disease. 

PMID- 25617664
TI  - Endocan--the new endothelial activation marker independently associated with
      soluble endothelial adhesion molecules in uraemic patients with cardiovascular
      disease.
AB  - OBJECTIVES: Endocan is a new marker of endothelial cell activation that mediates
      adhesion of leukocytes into endothelium. Soluble intercellular (sICAM-1) and
      vascular cellular (sVCAM-1) adhesion molecules play an important role in the
      prevalence of cardiovascular disease (CVD) in chronic kidney disease (CKD)
      patients. The aim of this study is to investigate whether endocan could affect
      the concentrations of sICAM-1 and sVCAM-1 in CKD patients, particularly in those
      with CVD. DESIGN AND METHODS: We evaluated plasma endocan, sICAM-1, sVCAM-1 and
      the markers of inflammation: high sensitivity C-reactive protein (hs CRP),
      interleukin-6, tumor necrosis factor-alpha (TNF-alpha) and their
      interrelationships in 53 CKD patients (both with and without CVD) and 29 healthy
      controls. RESULTS: Endocan, sICAM-1, sVCAM-1 and inflammatory markers were
      significantly higher in CKD patients than in controls, and patients with CVD had
      levels significantly higher (except interleukin-6 and TNF-alpha) than those
      without CVD. The presence of CVD, ferritin, TNF-alpha and SBP were the
      independent predictors of endocan levels in the whole CKD group. In this group,
      the weak relationship was between endocan and sICAM-1 and sVCAM-1, but age was
      the only independent predictor of these adhesion molecules. The strong
      association between endocan and sICAM-1 and sVCAM-1 was exclusively observed in
      subgroup with CVD, and the low % of lymphocytes followed by increased endocan was
      identified as the independent variables significantly associated with these
      soluble molecule levels. CONCLUSIONS: This study shows that plasma endocan is
      significantly increased and independently associated with sICAM-1 and sVCAM-1
      levels in CKD patients with cardiovascular complications.

PMID- 25617665
TI  - In vitro interference by acetaminophen, aspirin, and metamizole in serum
      measurements of glucose, urea, and creatinine.
AB  - OBJECTIVE: Here we aimed to investigate the in vitro effects of three analgesic
      antipyretic drugs frequently used in clinical practice in Mexico - acetaminophen
      (AAP), aspirin (ASA) and metamizole (MMZ) - on serum measurements of glucose,
      urea, and creatinine. DESIGN AND METHODS: Each analyte was measured in a base
      serum pool spiked with the drugs at subtherapeutic, therapeutic, and toxic doses.
      Serum glucose and urea were measured using the hexokinase/G-6PDH and urease/GLDH
      kinetic assays, respectively. Serum creatinine (SCr) was measured with a Jaffe
      procedure based on the alkaline-picrate reaction and with an enzymatic dry
      chemistry system. Measurements were carried out in IL-Monarch and Vitros DT60-II
      analyzers, respectively. Data were analyzed by the difference-paired interference
      test and by ANOVA. RESULTS: By the kinetic Jaffe/Monarch procedure, we found
      positive interference by the drugs on the SCr measurements and by only ASA for
      urea measurement. For creatinine measurements, the total errors (TEs) were 22
      51%, 18-105%, and 15-26% for AAP, ASA, and MMZ respectively, while for urea
      measurement the TE was 16-21% for ASA. A negative interference by MMZ on SCr (TE=
      47%), but no-interference for AAP or ASA, were found via the enzymatic/DT60-II
      system. CONCLUSIONS: In vitro positive interference induced by AAP, ASA, and MMZ
      (via the alkaline-picrate reaction), or negative interference by MMZ (via a dry
      chemistry system), on the SCr measurements highlights the importance of
      investigating all possible sources of variation that may alter the accuracy of
      the laboratory tests, in order to provide useful results for making medical
      decisions for optimal patient care.

PMID- 25617666
TI  - Gustatory insular cortex, aversive taste memory and taste neophobia.
AB  - Prior research indicates a role for the gustatory insular cortex (GC) in taste
      neophobia. Rats with lesions of the GC show much weaker avoidance to a novel and
      potentially dangerous taste than do neurologically intact animals. The current
      study used the retention of conditioned taste aversion (CTA) as a tool to
      determine whether the GC modulates neophobia by processing taste novelty or taste
      danger. The results show that GC lesions attenuate CTA retention (Experiment 1)
      and impair taste neophobia (Experiment 2). Given that normal CTA retention does
      not involve the processing of taste novelty, the pattern of results suggests that
      the GC is involved in taste neophobia via its function in processing the danger
      conveyed by a taste stimulus. 

PMID- 25617668
TI  - Inhibition of RANKL- and LPS-induced osteoclast differentiations by novel NF
      kappaB inhibitor DTCM-glutarimide.
AB  - We have isolated 9-methylstreptimidone from microorganism as a new NF-kappaB
      inhibitor. Later, we designed 3-[(dodecylthiocarbonyl) methyl]-glutarimide (DTCM
      glutarimide) as an analog of this compound, which shows anti-inflammatory
      activity in vivo. In the present research, we found that DTCM-glutarimide
      inhibited receptor activator of nuclear factor-kappaB ligand (RANKL)-induced
      osteoclast differentiation of mouse bone marrow-derived macrophages and RANKL- or
      lipopolysaccharide (LPS)-induced osteoclast differentiation of RAW 264.7 cells
      without any toxicity. It also inhibited the RANKL-induced NFATc1 expression.
      Upstream signaling involving phosphorylation of Akt and GSK-3beta was induced by
      RANKL, of which the signaling was inhibited by DTCM-glutarimide. Then DTCM
      glutarimide was confirmed to inhibit RANKL-induced NF-kappaB activity, possibly
      by inhibiting the Akt-mediated activation of IKK. Thus, DTCM-glutarimide
      inhibited osteoclastogenesis by blocking both the Akt-GSK3beta-NFATc1 and NF
      kappaB-NFATc1 pathways. DTCM-glutarimide may be a candidate as a chemotherapeutic
      agent for severe bone resorption diseases. 

PMID- 25617669
TI  - Can-Evo-Ens: Classifier stacking based evolutionary ensemble system for
      prediction of human breast cancer using amino acid sequences.
AB  - The diagnostic of human breast cancer is an intricate process and specific
      indicators may produce negative results. In order to avoid misleading results,
      accurate and reliable diagnostic system for breast cancer is indispensable.
      Recently, several interesting machine-learning (ML) approaches are proposed for
      prediction of breast cancer. To this end, we developed a novel classifier
      stacking based evolutionary ensemble system "Can-Evo-Ens" for predicting amino
      acid sequences associated with breast cancer. In this paper, first, we selected
      four diverse-type of ML algorithms of Naive Bayes, K-Nearest Neighbor, Support
      Vector Machines, and Random Forest as base-level classifiers. These classifiers
      are trained individually in different feature spaces using physicochemical
      properties of amino acids. In order to exploit the decision spaces, the
      preliminary predictions of base-level classifiers are stacked. Genetic
      programming (GP) is then employed to develop a meta-classifier that optimal
      combine the predictions of the base classifiers. The most suitable threshold
      value of the best-evolved predictor is computed using Particle Swarm Optimization
      technique. Our experiments have demonstrated the robustness of Can-Evo-Ens system
      for independent validation dataset. The proposed system has achieved the highest
      value of Area Under Curve (AUC) of ROC Curve of 99.95% for cancer prediction. The
      comparative results revealed that proposed approach is better than individual ML
      approaches and conventional ensemble approaches of AdaBoostM1, Bagging,
      GentleBoost, and Random Subspace. It is expected that the proposed novel system
      would have a major impact on the fields of Biomedical, Genomics, Proteomics,
      Bioinformatics, and Drug Development. 

PMID- 25617667
TI  - Novel non-calcemic secosteroids that are produced by human epidermal
      keratinocytes protect against solar radiation.
AB  - CYP11A1 hydroxylates the side chain of vitamin D3 (D3) in a sequential fashion
      [D3->20S(OH)D3->20,23(OH)2D3->17,20,23(OH)3D3], in an alternative to the
      classical pathway of activation [D3->25(OH)D3->1,25(OH)2D3]. The
      products/intermediates of the pathway can be further modified by the action of
      CYP27B1. The CYP11A1-derived products are biologically active with functions
      determined by the lineage of the target cells. This pathway can operate in
      epidermal keratinocytes. To further define the role of these novel secosteroids
      we tested them for protective effects against UVB-induced damage in human
      epidermal keratinocytes, melanocytes and HaCaT keratinocytes, cultured in vitro.
      The secosteroids attenuated ROS, H2O2 and NO production by UVB-irradiated
      keratinocytes and melanocytes, with an efficacy similar to 1,25(OH)2D3, while
      25(OH)D3 had lower efficacy. These attenuations were also seen to some extent for
      the 20(OH)D3 precursor, 20S-hydroxy-7-dehydrocholesterol. These effects were
      accompanied by upregulation of genes encoding enzymes responsible for defense
      against oxidative stress. Using immunofluorescent staining we observed that the
      secosteroids reduced the generation cyclobutane pyrimidine dimers in response to
      UVB and enhanced expression of p53 phosphorylated at Ser-15, but not at Ser-46.
      Additional evidence for protection against DNA damage in cells exposed to UVB and
      treated with secosteroids was provided by the Comet assay where DNA fragmentation
      was markedly reduced by 20(OH)D3 and 20,23(OH)2D3. In conclusion, novel
      secosteroids that can be produced by the action of CYP11A1 in epidermal
      keratinocytes have protective effects against UVB radiation. This article is part
      of a special issue entitled '17th Vitamin D Workshop'. 

PMID- 25617670
TI  - LGscore: A method to identify disease-related genes using biological literature
      and Google data.
AB  - Since the genome project in 1990s, a number of studies associated with genes have
      been conducted and researchers have confirmed that genes are involved in disease.
      For this reason, the identification of the relationships between diseases and
      genes is important in biology. We propose a method called LGscore, which
      identifies disease-related genes using Google data and literature data. To
      implement this method, first, we construct a disease-related gene network using
      text-mining results. We then extract gene-gene interactions based on co
      occurrences in abstract data obtained from PubMed, and calculate the weights of
      edges in the gene network by means of Z-scoring. The weights contain two values:
      the frequency and the Google search results. The frequency value is extracted
      from literature data, and the Google search result is obtained using Google. We
      assign a score to each gene through a network analysis. We assume that genes with
      a large number of links and numerous Google search results and frequency values
      are more likely to be involved in disease. For validation, we investigated the
      top 20 inferred genes for five different diseases using answer sets. The answer
      sets comprised six databases that contain information on disease-gene
      relationships. We identified a significant number of disease-related genes as
      well as candidate genes for Alzheimer's disease, diabetes, colon cancer, lung
      cancer, and prostate cancer. Our method was up to 40% more accurate than existing
      methods. 

PMID- 25617672
TI  - An analysis of FDA-approved drugs: natural products and their derivatives.
AB  - Natural products contribute greatly to the history and landscape of new molecular
      entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural
      products and their derivatives represent over one-third of all NMEs. Nearly one
      half of these are derived from mammals, one-quarter from microbes and one-quarter
      from plants. Since the 1930s, the total fraction of natural products has
      diminished, whereas semisynthetic and synthetic natural product derivatives have
      increased. Over time, this fraction has also become enriched with microbial
      natural products, which represent a significant portion of approved antibiotics,
      including more than two-thirds of all antibacterial NMEs. In recent years, the
      declining focus on natural products has impacted the pipeline of NMEs from
      specific classes, and this trend is likely to continue without specific
      investment in the pursuit of natural products. 

PMID- 25617671
TI  - Fusion-competent state induced by a C-terminal HIV-1 fusion peptide in
      cholesterol-rich membranes.
AB  - The replicative cycle of the human immunodeficiency virus type-1 begins after
      fusion of the viral and target-cell membranes. The envelope glycoprotein gp41
      transmembrane subunit contains conserved hydrophobic domains that engage and
      perturb the merging lipid bilayers. In this work, we have characterized the
      fusion-committed state generated in vesicles by CpreTM, a synthetic peptide
      derived from the sequence connecting the membrane-proximal external region (MPER)
      and the transmembrane domain (TMD) of gp41. Pre-loading cholesterol-rich vesicles
      with CpreTM rendered them competent for subsequent lipid-mixing with
      fluorescently-labeled target vesicles. Highlighting the physiological relevance
      of the lasting fusion-competent state, the broadly neutralizing antibody 4E10
      bound to the CpreTM-primed vesicles and inhibited lipid-mixing. Heterotypic
      fusion assays disclosed dependence on the lipid composition of the vesicles that
      acted either as virus or cell membrane surrogates. Lipid-mixing exhibited above
      all a critical dependence on the cholesterol content in those experiments. We
      infer that the fusion-competent state described herein resembles bona-fide
      perturbations generated by the pre-hairpin MPER-TMD connection within the viral
      membrane. 

PMID- 25617673
TI  - Does regulatory fit lead to more effective health communication? A systematic
      review.
AB  - Many of today's threats to public health arise from people's lifestyle. Hence,
      the public's compliance with advice given for health promotion and disease
      prevention has to be enhanced. Much research traces back the efficacy of health
      promotion messages to message qualities, while other work focuses on recipient
      qualities. Regulatory focus theory posits inter-individual differences in
      motivational orientation, namely a promotion or prevention focus, and offers a
      unique chance to look at message and recipient variables at the same time
      (Higgins, 1997). Whereas a promotion-focused individual tries to achieve desired
      end-states, someone with a prevention focus is rather vigilant. If individuals'
      goal pursuit strategies match their regulatory orientation, they experience
      regulatory fit, which increases the perceived persuasiveness of health messages
      (Higgins, 2000). Such a match can be evoked by particularly framed messages that
      highlight a person's regulatory orientation. Thus, the assumption of regulatory
      fit goes beyond the concept of gain- and loss-framing. To assess whether
      regulatory fit contributes to the effectiveness of health communication, a
      systematic review was conducted. An extensive systematic search led to the
      inclusion of 30 studies, for which data were extracted and quality appraised.
      Findings were summarized using narrative synthesis. Most studies (n = 23) were
      conducted in the USA and assessed the effects of regulatory fit on behavioral
      intention (n = 21). Nineteen experiments used samples of university students, and
      the health context chosen most often was a healthy diet (n = 7). Sixteen
      experiments manipulated regulatory orientation whereas chronic regulatory focus
      was measured ten times. The majority of studies confirmed that regulatory fit
      enhanced the effectiveness of health messages, which did not vary much across
      different health domains or outcomes. Regulatory fit is a promising approach for
      tailoring health messages as the synergy effects of regulatory fit increase their
      effectiveness.

PMID- 25617674
TI  - Innate immune sensing of HIV infection.
AB  - The ability to sense infections is primordial to preserve organisms. Immune cells
      express pathogen sensors that induct innate and adaptive immune responses.
      Understanding how HIV-1 infection defeats these responses in most individuals
      remains an outstanding challenge. Since HIV-1 targets immune cells, innate immune
      sensors are remarkably positioned at the nexus of viral replication and immunity.
      Here, we discuss recent studies that have revealed innate sensing mechanisms of
      HIV-1 infection in plasmacytoid dendritic cells, monocyte-derived dendritic
      cells, monocyte-derived macrophages, and CD4+ T cells. These studies help
      understand how HIV-1 avoids antiviral innate immune sensors and how it induces
      pathogenic processes. Ultimately, this may contribute to therapy and vaccines. 

PMID- 25617675
TI  - The importance of solidification stress on the redispersibility of solid
      nanocrystals loaded with harmine.
AB  - Due to limited understanding about effect of solidification stress on the
      redispersibility of drug nanocrystals, the impact of the different type and
      concentration of stabilizers and cryoprotectants, as well as the solidification
      temperature on the redispersibility of nanocrystals were systematically
      investigated. Harmine nanosuspensions were transformed into harmine solid
      nanocrystals (HAR-SNC) via different stress of solidification process including
      freezing, lyophilization and spray-drying. The effect of different concentrations
      of stabilizers and cryoprotectants on redispersibility of HAR-SNC was also
      investigated, respectively. The results showed that the redispersibility of HAR
      SNC at the aggressive freezing temperature stress was better more than those of
      conservative and moderate stress condition. The HPMC was effective enough to
      protect HAR-SNC from damage during lyophilization, which could homogeneously be
      adsorbed into the surface of nanocrystals to prevent the agglomerates. The
      sucrose and sorbitol achieved excellent performance that protected HAR-SNC from
      crystal growth during lyophilization. The CMS-Na played an outstanding role in
      protecting the HAR-SNC from breakage during spray-drying, due to the steric
      barrier effect of high viscosity polymeric stabilizers. It was concluded that HAR
      SNC was subjected to agglomeration or crystal growth during solidification, and
      the degree of agglomeration or crystal growth varied with the type and the
      amounts of stabilizers used, as well as stress conditions applied. The polymeric
      stabilizers were more effective to protect HAR-SNC from the damage during
      solidification process. 

PMID- 25617676
TI  - Inkjet printing of transdermal microneedles for the delivery of anticancer
      agents.
AB  - A novel inkjet printing technology is introduced as a process to coat metal
      microneedle arrays with three anticancer agents 5-fluororacil, curcumin and
      cisplatin for transdermal delivery. The hydrophilic graft copolymer Soluplus((r))
      was used as a drug carrier and the coating formulations consisted of drug-polymer
      solutions at various ratios. A piezoelectric dispenser jetted microdroplets on
      the microneedle surface to develop uniform, accurate and reproducible coating
      layers without any material losses. Inkjet printing was found to depend on the
      nozzle size, the applied voltage (mV) and the duration of the pulse (MUs). The
      drug release rates were determined in vitro using Franz type diffusion cells with
      dermatomed porcine skin. The drug release rates depended on the drug-polymer
      ratio, the drug lipophilicity and the skin thickness. All drugs presented
      increased release profiles (750 MUm skin thickness), which were retarded for 900
      MUm skin thickness. Soluplus assisted the drug release especially for the water
      insoluble curcumin and cisplatin due to its solubilizing capacity. Inkjet
      printing has been shown to be an effective technology for coating of metal
      microneedles which can then be used for further transdermal drug delivery
      applications.

PMID- 25617677
TI  - Development of a tumor tissue-mimicking model with endothelial cell layer and
      collagen gel for evaluating drug penetration.
AB  - The endothelial cells of vessels, the interstitial matrix and the distance
      between the tumor cells and vessels, are the major penetration barriers for
      intravenously administered anticancer drugs in reaching tumor cells after
      intravenous injection. The availability of a tumor tissue-mimicking model that
      includes both the endothelial cell layer and the extracellular matrix would be
      beneficial to assess drug penetration in early stages of drug development. Here,
      we propose a novel in vitro model for studying the above mentioned barriers.
      Human umbilical vein endothelial cells were cultured as a single layer on a
      collagen type-I coated permeable cell culture insert. After culturing for five
      days, the insert was superimposed on collagen type-I gel containing cancer cells.
      The system was evaluated for assessing penetration-enhancement by ultrasound
      triggered microbubble cavitation. Our model allowed visualization of the
      penetration distance of a model drug (fluorescein isothiocyanate - Dextran 500000
      conjugated, FD500) from the endothelial cell layer into the cancer cell
      containing collagen matrix upon different sonication treatments. Initial results
      showed that the model allows the visualization of drug penetration and that the
      endothelial cell layer is affecting this. The presented in vitro model aims to
      mimic vessels and stromal tissue in cancer, and thus can aid in the assessment of
      drug penetration in the case of tumor-targeted drug delivery, and in the
      reduction and refinement of animal studies. 

PMID- 25617678
TI  - Hidden persistence of salinity and productivity gradients shaping pelagic
      diversity in highly dynamic marine ecosystems.
AB  - While large-scale patterns of pelagic marine diversity are generally well
      described, they remain elusive at regional-scale given the high temporal and
      spatial dynamics of biological and local oceanographic processes. We here
      evaluated whether the main drivers of pelagic diversity can be more pervasive
      than expected at regional scale, using a meroplankton community of a frontal
      system in the Western Mediterranean. We evidence that regional biodiversity in a
      highly dynamic ecosystem can be summarized attending to both static (bathymetric)
      and ephemeral (biological and hydrographical) environmental axes of seascape.
      This pattern can be observed irrespectively of the regional hydroclimatic
      scenario with distance to coast, salinity gradient and chlorophyll a
      concentration being the main and recurrent drivers. By contrast, their effect is
      overridden in common analyses given that different non-linear effects are
      buffered between years of contrasting scenarios, emerging the influence of
      secondary effects on diversity. We conclude that community studies may reveal
      hidden persistent processes when they take into account different functional
      effects related to hydroclimatic variability. A better understanding of regional
      dynamics of the pelagic realm will improve our capability to forecast future
      responses of plankton communities as well as impacts of climate change on marine
      biodiversity. 

PMID- 25617679
TI  - Altered transcription levels of endocrine associated genes in two fisheries
      species collected from the Great Barrier Reef catchment and lagoon.
AB  - The Great Barrier Reef (GBR) is chronically exposed to agricultural run-off
      containing pesticides, many of which are known endocrine disrupting chemicals
      (EDCs). Here, we measure mRNA transcript abundance of two EDC biomarkers in wild
      populations of barramundi (Lates calcarifer) and coral trout (Plectropomus
      leopardus and Plectropomus maculatus). Transcription levels of liver vitellogenin
      (vtg) differed significantly in both species amongst sites with different
      exposures to agricultural run-off; brain aromatase (cyp19a1b) revealed some
      differences for barramundi only. Exposure to run-off from sugarcane that contains
      pesticides is a likely pathway given (i) significant associations between
      barramundi vtg transcription levels, catchment sugarcane land use, and river
      pesticide concentrations, and (ii) consistency between patterns of coral trout
      vtg transcription levels and pesticide distribution in the GBR lagoon. Given the
      potential consequences of such exposure for reproductive fitness and population
      dynamics, these results are cause for concern for the sustainability of fisheries
      resources downstream from agricultural land uses. 

PMID- 25617681
TI  - A novel method for preparation of MNP@CS-tethered coenzyme for coupled
      oxidoreductase system.
AB  - The immobilized cofactor NAD(H) is easily recovered from the reaction bulk, which
      is essential for repeated use of NAD(H) in the bioprocess catalyzed by NAD(H)
      dependent oxidoreductase. Here, a magnetic nanoparticle platform was designed to
      immobilize both of the NADH and the NAD(+). The design was based on chitosan
      coated magnetic nanoparticles (MNP@CS) which was activated by the EDC/NHS with
      the aid of azelaic acid as spacer. Interestingly, the succinimide group at the
      end of spacer arm catalyzed direct coupling of a carboxyl-terminal to the 6-amino
      group of the adenine residue of NAD(H). Our results indicated that 150 MUmol NADH
      and 50 MUmol NAD(+) was effectively attached to 1g MNP@CS at 25 degrees C in 120
      min and the prepared MNP@CS-NAD(H) showed good activity according to the coupling
      reaction of benzyl alcohol and acetaldehyde catalyzed by alcohol dehydrogenase.

PMID- 25617682
TI  - Bioactive fish collagen/polycaprolactone composite nanofibrous scaffolds
      fabricated by electrospinning for 3D cell culture.
AB  - One of the most challenging objectives of 3D cell culture is the development of
      scaffolding materials with outstanding biocompatibility and favorable mechanical
      strength. In this study, we fabricated a novel nanofibrous scaffold composed of
      fish collagen (FC) and polycaprolactone (PCL) blends by using the electrospinning
      method. Nanofibrous scaffolds were characterized using a scanning electron
      microscope (SEM), and it was revealed that the diameter of nanofibers decreased
      as FC content was increased in the FC/PCL composite nanofibers. The
      cytocompatibility of the FC/PCL scaffolds was evaluated by SEM, WST-1 assay,
      confocal microscopy, western blot, and RT-PCR. It was found that the scaffolds
      not only facilitated the adhesion, spreading, protrusions, and proliferation of
      thymic epithelial cells (TECs), but also stimulated the expression of genes and
      proteins involved in cell adhesion and T-cell development. Thus, these results
      suggest that the FC/PCL composite nanofibrous scaffolds will be a useful model of
      3D cell culture for TECs and may have wide applicability in the future for
      engineering tissues or organs. 

PMID- 25617680
TI  - Lipid domains in intact fiber-cell plasma membranes isolated from cortical and
      nuclear regions of human eye lenses of donors from different age groups.
AB  - The results reported here clearly document changes in the properties and the
      organization of fiber-cell membrane lipids that occur with age, based on electron
      paramagnetic resonance (EPR) analysis of lens membranes of clear lenses from
      donors of age groups from 0 to 20, 21 to 40, and 61 to 80 years. The physical
      properties, including profiles of the alkyl chain order, fluidity,
      hydrophobicity, and oxygen transport parameter, were investigated using EPR spin
      labeling methods, which also provide an opportunity to discriminate coexisting
      lipid domains and to evaluate the relative amounts of lipids in these domains.
      Fiber-cell membranes were found to contain three distinct lipid environments:
      bulk lipid domain, which appears minimally affected by membrane proteins, and two
      domains that appear due to the presence of membrane proteins, namely boundary and
      trapped lipid domains. In nuclear membranes the amount of boundary and trapped
      phospholipids as well as the amount of cholesterol in trapped lipid domains
      increased with the donors' age and was greater than that in cortical membranes.
      The difference between the amounts of lipids in domains uniquely formed due to
      the presence of membrane proteins in nuclear and cortical membranes increased
      with the donors' age. It was also shown that cholesterol was to a large degree
      excluded from trapped lipid domains in cortical membranes. It is evident that the
      rigidity of nuclear membranes was greater than that of cortical membranes for all
      age groups. The amount of lipids in domains of low oxygen permeability, mainly in
      trapped lipid domains, were greater in nuclear than cortical membranes and
      increased with the age of donors. These results indicate that the nuclear fiber
      cell plasma membranes were less permeable to oxygen than cortical membranes and
      become less permeable to oxygen with age. In clear lenses, age-related changes in
      the lens lipid and protein composition and organization appear to occur in ways
      that increase fiber cell plasma membrane resistance to oxygen permeation. 

PMID- 25617683
TI  - Production of lactate and acetate by Lactobacillus coryniformis subsp. torquens
      DSM 20004(T) in comparison with Lactobacillus amylovorus DSM 20531(T).
AB  - Lactobacillus coryniformis subsp. torquens DSM20004(T) is a d-lactate producer,
      with a portion of the d-lactate higher than 99.9% of total lactic acid produced.
      Acetate was identified as the second end-product that appeared at the end of the
      exponential growth phase in MRS medium when glucose concentration dropped to
      38.41mM (6.92g/L). The acetate production was prolonged to the stationary phase,
      while the concentration of d-lactate remained constant. Other end-products were
      not identified by HPLC method. The known metabolic pathways of glucose
      fermentation in lactic acid bacteria do not produce the particular combination of
      these two end-products, but besides lactate and acetate also formate, ethanol and
      CO2 are produced. For comparison, the production of lactate and acetate by a d-/l
      lactate producer Lactobacillus amylovorus DSM 20531(T) was also investigated.
      This strain produced equimolar quantities of d- and l-lactate in the MRS medium.
      Acetate was produced only when initial concentration of glucose was 55.51mM
      (10g/L) and production started in the exponential phase when concentration of
      glucose dropped to 35.52mM (6.40g/L). Similar behavior was observed with the
      initial concentration of maltose of 29.21mM (10g/L). An unstructured mathematical
      model was established for the bioprocess simulation. 

PMID- 25617684
TI  - Construction of the recombinant broad-host-range plasmids providing their
      bacterial hosts arsenic resistance and arsenite oxidation ability.
AB  - The plasmid pSinA of Sinorhizobium sp. M14 was used as a source of functional
      phenotypic modules, encoding proteins involved in arsenite oxidation and arsenic
      resistance, to obtain recombinant broad-host-range plasmids providing their
      bacterial hosts arsenic resistance and arsenite oxidative ability. An arsenite
      oxidation module was cloned into pBBR1MCS-2 vector yielding plasmid vector pAIO1,
      while an arsenic resistance module was cloned into pCM62 vector yielding plasmid
      pARS1. Both plasmid constructs were introduced (separately and together) into the
      cells of phylogenetically distant (representing Alpha-, Beta-, and
      Gammaproteobacteria) and physiologically diversified (unable to oxidize arsenite
      and susceptible/resistant to arsenite and arsenate) bacteria. Functional analysis
      of the modified strains showed that: (i) the plasmid pARS1 can be used for the
      construction of strains with an increased resistance to arsenite [up to 20mM of
      As(III), (ii) the presence of the plasmid pAIO1 in bacteria previously unable to
      oxidize As(III) to As(V), contributes to the acquisition of arsenite oxidation
      abilities by these cells, (iii) the highest arsenite utilization rate are
      observed in the culture of strains harbouring both the plasmids pAIO1 and pARS1,
      (iv) the strains harbouring the plasmid pAIO1 were able to grow on arsenic
      contaminated mine waters (~ 3.0 mg As L(-1)) without any supplementation.

PMID- 25617685
TI  - White matter alterations are associated with suicide attempt in patients with
      panic disorder.
AB  - BACKGROUND: Panic disorder (PD) is associated with an increased risk of suicide
      attempt (SA). However, no study has examined the neural correlates of SA in PD.
      The goal of this study was to evaluate alterations in white matter (WM) and gray
      matter (GM) in patients with PD with and without a history of SA. METHODS: Twelve
      patients with PD and a history of SA (PD+SA) and 24 patients with PD and no
      history of SA (PD-SA) underwent magnetic resonance imaging (MRI). All patients
      completed the Scale for Suicide Ideation (SSI), the Panic Disorder Severity Scale
      (PDSS), and the Beck Depression Inventory (BDI). The groups were matched for age,
      sex, and BDI and PDSS scores. Voxel-based morphometry and tract-based spatial
      statistics were used for the imaging analysis. RESULTS: Although no GM or WM
      volume differences were observed, increased fractional anisotropy (FA) values
      were found in the WM tracts of the PD+SA group compared with the PD-SA group. The
      regions with increased FA included the internal capsule, splenium of the corpus
      callosum, superior and posterior corona radiata, thalamic radiations, sagittal
      stratum, and superior longitudinal fasciculus. The FA values for the internal
      capsule and thalamic radiations were significantly correlated with the SSI scores
      in the PD+SA group. LIMITATIONS: The results should be considered preliminary due
      to the relatively small sample size. CONCLUSIONS: Our data suggest that the
      aberrant WM integrity of the internal capsule and thalamic radiations may be the
      significant neural correlate of SA in patients with PD.

PMID- 25617686
TI  - Suicide following self-harm: findings from the Multicentre Study of self-harm in
      England, 2000-2012.
AB  - BACKGROUND: Self-harm is a key risk factor for suicide and it is important to
      have contemporary information on the extent of risk. METHODS: Mortality follow-up
      to 2012 of 40,346 self-harm patients identified in the three centres of the
      Multicentre Study of Self-harm in England between 2000 and 2010. RESULTS:
      Nineteen per cent of deaths during the study period (N=2704) were by suicide,
      which occurred in 1.6% of patients (2.6% of males and 0.9% of females), during
      which time the risk was 49 times greater than the general population risk.
      Overall, 0.5% of individuals died by suicide in the first year, including 0.82%
      of males and 0.27% of females. While the absolute risk of suicide was greater in
      males, the risk relative to that in the general population was higher in females.
      Risk of suicide increased with age. While self-poisoning had been the most
      frequent method of self-harm, hanging was the most common method of subsequent
      suicide, particularly in males. The number of suicides was probably a
      considerable underestimate as there were also a large number of deaths recorded
      as accidents, the majority of which were poisonings, these often involving
      psychotropic drugs. LIMITATIONS: The study was focussed entirely on hospital
      presenting self-harm. CONCLUSIONS: The findings underline the importance of
      prevention initiatives focused on the self-harm population, especially during the
      initial months following an episode of self-harm. Estimates using suicide and
      open verdicts may underestimate the true risk of suicide following self-harm;
      inclusion of accidental poisonings may be warranted in future risk estimates.

PMID- 25617687
TI  - Allatotropin inhibits juvenile hormone biosynthesis by the corpora allata of
      adult Bombyx mori.
AB  - Juvenile hormone (JH) synthesis by the corpora allata (CA) does not occur during
      the pupal stage in both male and female Bombyx mori but begins shortly before
      adult ecdysis and thereafter only in females. JH biosynthesis in female adults
      was prevented by allatotropin (AT) through the corpora cardiaca (CC) and the
      tightly attached oesophagus before adult ecdysis, but after ecdysis, removal of
      the CC had little effect and only the oesophagus was necessary for AT to prevent
      JH synthesis. AT could not prevent JH synthesis by the CA alone in either stage.
      Short neuropeptide F (sNPF) acted directly on the CA, preventing JH biosynthesis
      without preventing the JH biosynthetic enzymes before adult ecdysis, but had
      little effect after ecdysis, indicating that the action of AT was not via sNPF.
      The inhibition of JH synthesis by AT was indirect. Both AT and a factor(s) from
      the AT-stimulated oesophagus through the CC were necessary for the inhibitory
      action, which was due to the prevention of some of the JH biosynthetic enzymes.
      These results clearly show that AT prevents JH synthesis in adult CA in B. mori,
      although AT stimulates JH biosynthesis by the CA in several insect species. 

PMID- 25617688
TI  - Characterization of Melanoplus sanguinipes oviposition stimulating protein
      expression and re-examination of its potential role in stimulating oviposition.
AB  - Melanoplussanguinipes oviposition stimulating protein (MsOSP) was characterized
      and its role in stimulating oviposition in virgin females was examined. A 967nt
      MsOSP mRNA sequence with homology to previously characterized N-terminal amino
      acid sequence data for MsOSP was identified in a RNAseq library generated from an
      mRNA pool from the long hyaline tubule (LHT) of the male accessory gland complex.
      This transcript contained a predicted 729nt open reading frame encoding the 242aa
      putative MsOSP protein and had the second highest read abundance in the library.
      The MsOSP transcript was detected exclusively in the LHT tissue of adult males
      and its abundance increased with time until 7 days post-eclosion. Western blot
      analysis using an anti-MsOSP antibody showed high levels of MsOSP protein in the
      LHT luminal secretions of virgin males and to a lesser degree was associated with
      the aedeagus and ejaculatory duct. MsOSP was shown to be a major protein
      component of the spermatophore packet transferred from the male to female during
      copulation. However, only minor amounts of MsOSP could be detected in the female
      bursa, spermatheca and oviduct. Intrahemocoelic injection of LHT luminal protein
      into mature virgin females stimulated oviposition in ~ 65% of females. A similar
      but non-significant trend was observed upon injection of purified recombinant
      MsOSP protein, and immunoprecipitation of LHT protein with anti-MsOSP antibody
      led to abrogation of oviposition stimulation upon injection of mature virgin
      females. Despite the demonstration of stimulation of oviposition upon
      intrahemocoelic injection of LHT-derived-MsOSP into mature virgin females, the
      potential mode of action of MsOSP in this process remains to be determined. MsOSP
      cannot be detected in the tissues other than the bursa, spermatheca and oviduct
      of female grasshoppers and relatively large quantities of MsOSP are required to
      stimulate oviposition upon injection.

PMID- 25617689
TI  - Molecular characterization and RNA interference analysis of vitellogenin receptor
      from Nilaparvata lugens (Stal).
AB  - Vitellogenin receptors (VgRs), members of the low-density lipoprotein receptor
      (LDLR) superfamily, are responsible for taking vitellogenin (Vg) into developing
      oocytes. Here the first full-length VgR cDNA from a hemipteran insect, the brown
      planthopper (Nilaparvata lugens), was cloned and sequenced. The complete mRNA
      sequence was 6174 bp in length with an open reading frame (ORF) of 5796 bp
      encoding 1931 amino acid residues. N. lugens VgR (NlVgR) contained two ligand
      binding domains with five LDLR Class A cysteine-rich repeats in the first domain
      and eight in the second domain, which was similar to other insect VgRs. NlVgR was
      specifically expressed in the ovary, and the mRNA level started to increase after
      adult female emergence, with a peak on day 7 in the adult stage, and then
      declined. Western blot analysis of NlVgR protein revealed an ovary-specific
      expression pattern, which was consistent with NlVgR transcript detection.
      Injection with NlVgR double-stranded RNA (dsRNA) significantly disturbed NlVgR,
      which led to a decrease in NlVg protein content in the ovaries, an accumulation
      of NlVg protein in the hemolymph, the arrested development of ovaries, and the
      failure of insects to reproduce. Besides, NlVgR expression was significantly
      upregulated after the topical application of juvenile hormone (JH) III. These
      results suggest that VgR is critical for Vg uptaking of oocytes and it plays an
      important role in insect fecundity.

PMID- 25617691
TI  - Identification of amino acids that are selectively involved in Gi/o activation by
      rat melanin-concentrating hormone receptor 1.
AB  - Many G-protein-coupled receptors (GPCRs) are known to functionally couple to
      multiple G-protein subfamily members. Although promiscuous G-protein coupling
      enables GPCRs to mediate diverse signals, only a few GPCRs have been identified
      with differential determinants for coupling to distinct Galpha proteins.
      Mammalian melanin-concentrating hormone receptor 1 (MCHR1) couples to dual G
      protein subfamilies. However, the selectivity mechanisms between MCHR1 and
      different subtypes of Galpha proteins are unclear. Our previous studies
      demonstrated that mammalian MCHR1 couples to both Gi/o and Gq, whereas goldfish
      MCHR1 exclusively couples to Gq. In this study, we analyzed multiple sequence
      alignments between rat and goldfish MCHR1s, and designed three multisubstituted
      mutants of rat MCHR1 by replacing corresponding residues with those in goldfish
      MCHR1, focusing on regions around the cytosolic intracellular loops. By
      measurement of intracellular Ca(2+) mobilization, we found that two MCHR1
      mutants, i2_6sub and i3_6sub, which contained six simultaneously substituted
      residues in the second intracellular loop or a combination of substituted
      residues in the third intracellular loop and fifth transmembrane domain,
      respectively, significantly reduced Gi/o-sensitive pertussis toxin responsiveness
      without altering Gq-mediated activity. Analyses of 10 other substitutions
      revealed that the multiple substitutions in i2_6sub and i3_6sub were necessary
      for Gi/o-selective responses. As judged by Gi/o-dependent GTPgammaS binding and
      cyclic AMP assays, i2_6sub and i3_6sub elicited phenotypes for impaired Gi/o
      mediated signaling. We also monitored the dynamic mass redistribution (DMR) in
      living cells, which reveals receptor activity as an optical trace containing
      activation of all GPCR coupling classes. Cells transfected with i2_6sub or
      i3_6sub exhibited reduced Gi/o-mediated DMR responses compared with those
      transfected with MCHR1. These data suggest that two different regions
      independently affect the Gi/o-protein preference, and that multiple residues
      comprise a conformation favoring Gi/o-protein coupling and subsequently result in
      Gi/o-selective signaling.

PMID- 25617690
TI  - A small molecule PAI-1 functional inhibitor attenuates neointimal hyperplasia and
      vascular smooth muscle cell survival by promoting PAI-1 cleavage.
AB  - Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of urokinase-and
      tissue-type plasminogen activators (uPA and tPA), is an injury-response gene
      implicated in the development of tissue fibrosis and cardiovascular disease. PAI
      1 mRNA and protein levels were elevated in the balloon catheter-injured carotid
      and in the vascular smooth muscle cell (VSMC)-enriched neointima of ligated
      arteries. PAI-1/uPA complex formation and PAI-1 antiproteolytic activity can be
      inhibited, via proteolytic cleavage, by the small molecule antagonist tiplaxtinin
      which effectively increased the VSMC apoptotic index in vitro and attenuated
      carotid artery neointimal formation in vivo. In contrast to the active full
      length serine protease inhibitor (SERPIN), elastase-cleaved PAI-1 (similar to
      tiplaxtinin) also promoted VSMC apoptosis in vitro and similarly reduced
      neointimal formation in vivo. The mechanism through which cleaved PAI-1 (CL-PAI
      1) stimulates apoptosis appears to involve the TNF-alpha family member TWEAK (TNF
      alpha weak inducer of apoptosis) and it's cognate receptor, fibroblast growth
      factor (FGF)-inducible 14 (FN14). CL-PAI-1 sensitizes cells to TWEAK-stimulated
      apoptosis while full-length PAI-1 did not, presumably due to its ability to down
      regulate FN14 in a low density lipoprotein receptor-related protein 1 (LRP1)
      dependent mechanism. It appears that prolonged exposure of VSMCs to CL-PAI-1
      induces apoptosis by augmenting TWEAK/FN14 pro-apoptotic signaling. This work
      identifies a critical, anti-stenotic, role for a functionally-inactive (at least
      with regard to its protease inhibitory function) cleaved SERPIN. Therapies that
      promote the conversion of full-length to cleaved PAI-1 may have translational
      implications.

PMID- 25617692
TI  - Telemedicine for patients with epilepsy: a pilot experience.
AB  - We aimed to describe our preliminary experience with the telemedicine (TM)
      seizure clinic. A retrospective database analysis for the TM seizure visits
      between January 2009 and January 2012 was performed. Each subject's age, gender,
      epilepsy syndrome, seizure types, and outcome were identified. The antiepileptic
      drug (AED) regimen at each visit was noted, as well as instances where surgical
      therapies and admission for monitoring were discussed. We identified a total of
      74 encounters with 24 patients. Fifteen subjects (62.5%) had focal epilepsy,
      whereas seven (29%) had generalized epilepsy. Seven patients (29%) experienced
      one seizure type, 14 (58.5%) had two seizure types, and five (12.5%) had three or
      more seizure types. Thirty-two out of the 74 encounters (43%) resulted in some
      change in the AED regimen. Surgical therapeutic options were discussed in 35% of
      the visits. Two-thirds of subjects were either seizure-free or improved by the
      last encounter. The no-show rate was only 11%. We were able to deliver follow-up
      care through a TM model to patients with epilepsy with a wide spectrum of
      syndromes and severity. We believe that TM improves access to specialized care
      for patients with epilepsy living in rural areas. 

PMID- 25617693
TI  - Understanding the importance of glycosylated threonine and stereospecific action
      of Drosocin, a Proline rich antimicrobial peptide.
AB  - Glycosylation is an essential post-translational modification for few
      antimicrobial peptides of Proline rich class. In the present study we have shown
      the importance of Thr glycosylation over Ser glycosylation in Drosocin.
      Difference of a methyl group makes glycosylated-Thr preferred over glycosylated
      Ser and renders higher activity to the peptide, probably due to the rigid
      conformation provided by the glycosylated-Thr. The structural rigidity provided
      by glycosylated-Thr to Drosocin backbone was mimicked by substituting
      glycosylated-Thr11, Ser7 and Ser12 with Pro residues. The designed non
      glycosylated analogue, P(7)P(11)P(12)-Drosocin, exhibited functional and
      structural properties similar to that of the native monoglycosylated peptide. The
      functional importance of stereospecificity of amino acids and sugar was further
      explored. Interestingly, (all D) p(7)p(11)p(12)-Drosocin failed to exhibit
      antimicrobial activity but had comparable binding affinity to DnaK, one of the
      proposed targets for Proline rich class of antibacterial peptides, as that of its
      L counterpart. However, Drosocin containing either L or D enantiomeric sugar,
      displayed antimicrobial activity and binding affinity to bacterial heat shock
      protein, DnaK. The flow cytometry (FACS) experiments revealed the internalization
      of Drosocins bearing enantiomeric sugars and P(7)P(11)P(12)-Drosocin but not of
      its d-enantiomer into bacteria suggesting the importance of stereospecificity of
      amino acids for membrane entry. Once internalized both enantiomeric peptides may
      behave similarly. This assumption was corroborated by in vitro activity of (all
      D) p(7)p(11)p(12)-Drosocin in cell free assay where it abrogated
      transcription/translation pathway similar to l-enantiomer but could not inhibit
      the same in whole cell assay. These research findings provide insights into the
      mode of action of Proline rich class of antibacterial peptides and guidelines for
      designing functionally equivalent non-glycosylated analogues of glycosylated
      antibacterial peptides. 

PMID- 25617695
TI  - Linear and branched alkyl-esters and amides of gallic acid and other (mono-, di-
      and tri-) hydroxy benzoyl derivatives as promising anti-HCV inhibitors.
AB  - Linear and branched compounds that contain two, three or five units of galloyl
      (3,4,5-trihydroxybenzoyl) or its isomer 2,3,4-trihydroxybenzoyl, as well as other
      mono- or dihydroxybenzoyl moieties have been synthesized. These molecules have
      been evaluated for their in vitro inhibitory effects against a wide panel of
      viruses showing preferential activity against HIV and HCV. Our structure-activity
      relationship studies demonstrated that the 2,3,4-trihydroxybenzoyl moiety
      provides better antiviral activities than the galloyl (3,4,5-trihydroxybenzoyl)
      moiety that is present in natural green tea catechins. This observation can be of
      interest for the further rational exploration of compounds with anti-HCV/HIV
      properties. The most notable finding with respect to HIV is that the tripodal
      compounds 43 and 45, with three 2,3,4-trihydroxybenzoyl moieties, showed higher
      activities than linear compounds with only one or two. With respect to HCV, the
      linear compounds, 52 and 41, containing a 12 polymethylene chain and two 2,3 di-
      or 2,3,4 tri-hydroxybenzoyl groups respectively at the ends of the molecule
      showed good antiviral efficiency. Furthermore, the anti-HCV activity of both
      compounds was observed at concentrations well below the cytotoxicity threshold. A
      representative member of these compounds, 41, showed that the anti-HCV activity
      was largely independent of the genetic make-up of the HCV subgenomic replicon and
      cell lines used. 

PMID- 25617694
TI  - Evolution in medicinal chemistry of ursolic acid derivatives as anticancer
      agents.
AB  - Currently, there is a renewed interest in common dietaries and plant-based
      traditional medicines for the prevention and treatment of cancer. In the search
      for potential anticancer agents from natural sources, ursolic acid (UA), a
      pentacyclic triterpenoid widely found in various medicinal herbs and fruits,
      exhibits powerful biological effects including its attractive anticancer activity
      against various types of cancer cells. However, the limited solubility, rapid
      metabolism and poor bioavailability of UA restricted its further clinical
      applications. In the past decade, with substantial progress toward the
      development of new chemical entities for the treatment of cancer, numerous UA
      derivatives have been designed and prepared to overcome its disadvantages.
      Despite extensive effort, discovery of effective UA derivatives has so far met
      with only limited success. This review summarizes the current status of the
      structural diversity and evolution in medicinal chemistry of UA analogues and
      provides a detailed discussion of future direction for further research in the
      chemical modifications of UA. 

PMID- 25617696
TI  - The successful application of systems approaches in plant biology.
AB  - Plant biology has had longstanding successes from applying mathematical models to
      plant systems. Of the >160 models that have been developed to date, a closer
      study is made of crop models and more recent plant models. The latter focus on
      hormone response networks, metabolism, circadian clock, biomechanics of growth
      and new organ development. The multicellular and multiscale models have provided
      important and novel insights into the regulation of hormone distribution, tissue
      development and environmental sensing. Finally, the challenges faced when
      establishing multidisciplinary teams are introduced along with successful
      management strategies and techniques to overcome them. 

PMID- 25617698
TI  - Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in
      Dahl rats.
AB  - BACKGROUND: The study was designed to explore the significance of endogenous H2S
      in the development of high-salt-induced hypertension in rats. METHODS: High-salt
      induced hypertension rat model was made by feeding Dahl rat high-salt diet
      containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure
      in rats were observed. Endogenous H2S content and expression of cystathionine
      beta-lyase (CBS), cystathionine gamma-lyase and mercaptopyruvate
      sulfurtransferase in renal tissues were detected. Mechanisms for the impact of
      high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1alpha pathway.
      The effect of H2S on RAS in serum and renal tissue of rats were tested. RESULTS:
      High-salt reduced endogenous H2S content and inhibited the expression of CBS in
      renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt
      sensitive hypertension, reversed aortic structural remodeling and inhibited
      activation of the RAS system in renal tissues in Dahl rats. Expression of HIF
      1alpha was decreased but expression of PHD2 was increased in renal tissue of Dahl
      rats with high-salt diet, whereas they did not alter in renal tissue of SD rats
      with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1alpha
      degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl
      rats with high-salt. In contrast, inhibitor of HIF-1alpha activity decreased the
      CBS/H2S pathway in the renal tissue of SD rats treated with high-salt.
      CONCLUSIONS: Down-regulated CBS/H2S pathway in renal tissues under high-salt
      insult might be an important pathogenesis of salt-sensitive hypertension.

PMID- 25617699
TI  - Assessing the concentrations and risks of toxicity from the antibiotics
      ciprofloxacin, sulfamethoxazole, trimethoprim and erythromycin in European
      rivers.
AB  - This study evaluated the potential concentrations of four antibiotics:
      ciprofloxacin (CIP), sulfamethoxazole (SUF), trimethoprim (TRI) and erythromycin
      (ERY) throughout the rivers of Europe. This involved reviewing national
      consumption rates together with assessing excretion and sewage treatment removal
      rates. From this information, it was possible to construct best, expected and
      worst case scenarios for the discharge of these antibiotics into rivers.
      Consumption data showed surprising variations, up to 200-fold in the popularity
      of different antibiotics across different European nations. Using the water
      resources model GWAVA which has a spatial resolution of approximately 6*9 km,
      river water concentrations throughout Europe were predicted based on 31-year
      climate data. The modelled antibiotic concentrations were within the range of
      measurements reported previously in European effluents and rivers. With the
      expected scenario, the predicted annual-average antibiotic concentrations ranged
      between 0 and 10 ng/L for 90% by length of surface waters. In the worst case
      scenario concentrations could reach between 0.1 and 1 MUg/L at the most exposed
      locations. As both predicted and observed sewage effluent concentrations were
      below reported effect levels for the most sensitive aquatic wildlife, no direct
      toxicity in rivers is expected. Predicted river concentrations for CIP and ERY
      were closest to effect levels in wildlife, followed by SUF which was 2-3 orders
      of magnitude lower. TRI appeared to be of the least concern with around 6 orders
      of magnitude difference between predicted and effect levels. However, mixture
      toxicity may elevate this risk and antibiotic levels of 0.1-1 MUg/L in hotspots
      may contribute to local environmental antibiotic resistance in microorganisms.

PMID- 25617697
TI  - Mathematical modeling of acid-base physiology.
AB  - pH is one of the most important parameters in life, influencing virtually every
      biological process at the cellular, tissue, and whole-body level. Thus, for
      cells, it is critical to regulate intracellular pH (pHi) and, for multicellular
      organisms, to regulate extracellular pH (pHo). pHi regulation depends on the
      opposing actions of plasma-membrane transporters that tend to increase pHi, and
      others that tend to decrease pHi. In addition, passive fluxes of uncharged
      species (e.g., CO2, NH3) and charged species (e.g., HCO3(-), [Formula: see text]
      ) perturb pHi. These movements not only influence one another, but also perturb
      the equilibria of a multitude of intracellular and extracellular buffers. Thus,
      even at the level of a single cell, perturbations in acid-base reactions,
      diffusion, and transport are so complex that it is impossible to understand them
      without a quantitative model. Here we summarize some mathematical models
      developed to shed light onto the complex interconnected events triggered by acids
      base movements. We then describe a mathematical model of a spherical cells-which
      to our knowledge is the first one capable of handling a multitude of buffer
      reactions-that our team has recently developed to simulate changes in pHi and pHo
      caused by movements of acid-base equivalents across the plasma membrane of a
      Xenopus oocyte. Finally, we extend our work to a consideration of the effects of
      simultaneous CO2 and HCO3(-) influx into a cell, and envision how future models
      might extend to other cell types (e.g., erythrocytes) or tissues (e.g., renal
      proximal-tubule epithelium) important for whole-body pH homeostasis. 

PMID- 25617700
TI  - Impact of papyrus wetland encroachment on spatial and temporal variabilities of
      stream flow and sediment export from wet tropical catchments.
AB  - During the past decades, land use change in the Lake Victoria basin has
      significantly increased the sediment fluxes to the lake. These sediments as well
      as their associated nutrients and pollutants affect the food and water security
      of millions of people in one of Africa's most densely populated regions. Adequate
      catchment management strategies, based on a thorough understanding of the factors
      controlling runoff and sediment discharge are therefore crucial. Nonetheless,
      studies on the magnitude and dynamics of runoff and sediment discharge are very
      scarce for the Lake Victoria basin and the African Rift region. We therefore
      conducted runoff discharge and sediment export measurements in the Upper Rwizi, a
      catchment in Southwest Uganda, which is representative for the Lake Victoria
      basin. Land use in this catchment is characterized by grazing area on the high
      plateaus, banana cropping on the slopes and Cyperus papyrus L. wetlands in the
      valley bottoms. Due to an increasing population pressure, these papyrus wetlands
      are currently encroached and transformed into pasture and cropland. Seven
      subcatchments (358 km2-2120 km2), with different degrees of wetland encroachment,
      were monitored during the hydrological year June 2009-May 2010. Our results
      indicate that, due to their strong buffering capacity, papyrus wetlands have a
      first-order control on runoff and sediment discharge. Subcatchments with intact
      wetlands have a slower rainfall-runoff response, smaller peak runoff discharges,
      lower rainfall-runoff ratios and significantly smaller suspended sediment
      concentrations. This is also reflected in the measured annual area-specific
      suspended sediment yields (SYs): subcatchments with encroached papyrus swamps
      have SY values that are about three times larger compared to catchments with
      intact papyrus vegetation (respectively 106-137 ton km(-2) y(-1) versus 34-37 ton
      km(-2) y(-1)). We therefore argue that protecting and (where possible)
      rehabilitating these papyrus wetlands should be a corner stone of catchment
      management strategies in the Lake Victoria basin.

PMID- 25617701
TI  - Development of eukaryotic zoospores within polycyclic aromatic hydrocarbon (PAH)
      polluted environments: a set of behaviors that are relevant for bioremediation.
AB  - In this study, we assessed the development (formation, taxis and settlement) of
      eukaryotic zoospores under different regimes of exposure to polycyclic aromatic
      hydrocarbons (PAHs), which imitated environmental scenarios of pollution and
      bioremediation. With this aim, we used an oomycete, Pythium aphanidermatum, as a
      source of zoospores and two PAH-degrading bacteria (Mycobacterium gilvum VM552
      and Pseudomonas putida G7). The oomycete and both bacteria were not antagonistic,
      and zoospore formation was diminished only in the presence of the highest
      bacterial cell density (10(8)-10(10) colony-forming units mL(-1)). A negative
      influence of PAHs on zoospore formation and taxis was observed when PAHs were
      exposed in combination with organic solutions and polar solvents. Co-exposure of
      PAHs with non-polar solvents [hexadecane (HD) and 2,2,4,4,6,8,8-heptamethylnonane
      (HMN)] did not affect zoospore settlement at the interfaces of the organic
      solvents and water. However, zoospores settled and created mycelial networks only
      at HD-water interfaces. Both bacteria diminished the toxic influence of PAHs on
      zoospore formation and taxis, and they did not interrupt zoospore settlement. The
      results suggest that zoospore development could be applicable for toxicity
      assessment of PAHs and enhancement of their bioavailability. Microbial
      interactions during both swimming modes and community formation at pollutant
      interfaces were revealed as major factors that have potential relevance to
      bioremediation.

PMID- 25617702
TI  - The composition, spatial patterns, and influencing factors of atmospheric wet
      nitrogen deposition in Chinese terrestrial ecosystems.
AB  - Atmospheric nitrogen (N) deposition is an important component of the global N
      cycle, and is a key source of biologically available N. Understanding the spatio
      temporal patterns and influencing factors of N deposition is essential to
      evaluate its ecological effects on terrestrial ecosystems, and to provide a
      scientific basis for global change research. In this study, we monitored the
      monthly atmospheric N deposition in rainfall at 41 stations from the Chinese
      Ecosystem Research Network through measuring total N (TN), total dissolved N
      (TDN), ammonium (NH4+-N), and nitrate (NO3--N). The results showed that the
      atmospheric wet deposition of TDN, NH4+-N, and NO3--N were 13.69, 7.25, and 5.93
      kg N ha(-1) yr(-1), respectively. The deposition of TN and total particulate N
      (TPN) was 18.02 and 4.33 kg N ha(-1) yr(-1) respectively, in 2013. TPN accounted
      for 24% of TN, while NH4+-N and NO3--N made up 40% and 33%, respectively,
      confirming the assumption that atmospheric wet N deposition would be
      underestimated without particulate N in rainfall. The N deposition was higher in
      Central and Southern China, and lower in North-west, North-east, Inner Mongolia,
      and Qinghai-Tibet regions. Precipitation, N fertilizer use, and energy
      consumption were significantly correlated with wet N deposition (all p<0.01).
      Models that included precipitation and N fertilizer can explain 80-91% of the
      variability in wet N deposition. Our findings reveal, for the first time, the
      composition of the wet N deposition in China at different scales and highlight
      the importance of TPN.

PMID- 25617703
TI  - Stanovich's arguments against the "adaptive rationality" project: An assessment.
AB  - This paper discusses Stanovich's appeal to individual differences in reasoning
      and decision-making to undermine the "adaptive rationality" project put forth by
      Gigerenzer and his co-workers. I discuss two different arguments based on
      Stanovich's research. First, heterogeneity in the use of heuristics seems to be
      at odds with the adaptationist background of the project. Second, the existence
      of correlations between cognitive ability and susceptibility to cognitive bias
      suggests that the "standard picture of rationality" (Stein, 1996, 4) is
      normatively adequate. I argue that, as matters stand, none of the arguments can
      be seen as fully compelling. Nevertheless, my discussion is not only critical of
      Stanovich's research, as I also show that (and how) his research can push forward
      the so-called "rationality debate" by encouraging greater theoretical and
      experimental work. 

PMID- 25617704
TI  - Risk Factors for Development of New or Worsened Pressure Ulcers Among Patients in
      Inpatient Rehabilitation Facilities in the United States: Data From the Uniform
      Data System for Medical Rehabilitation.
AB  - BACKGROUND: Documentation of a new or worsened pressure ulcer is a new, required
      quality indicator for all inpatient rehabilitation facilities (IRFs) in the
      United States; however, there is little research regarding risk factors for
      pressure ulcers among patients seen in IRFs. OBJECTIVE: To examine the risk
      factors for development of a new or worsened pressure ulcer among patients seen
      in IRFs. DESIGN: A retrospective cohort study. SETTING: IRFs in the United
      States. PARTICIPANTS: IRF patients more than 18 years of age, with documented new
      or worsened pressure ulcer during their rehabilitation stay (n = 2766) and IRF
      patients with no new or worsened pressure ulcer documented from admission to
      discharge (n = 190,996) discharged October 2008 to September 2011, included in
      the Uniform Data System for Medical Rehabilitation database. METHODS: Multiple
      logistic regression analysis was used to estimate risk factors for the
      development of a new or worsened pressure ulcer utilizing data captured in the
      Centers for Medicare and Medicaid Services (CMS) payment document. Examined were
      demographic variables, including age and gender, medical variables, including
      impairment type and presence of comorbidities, and functional status, as measured
      through the Functional Independence Measure (FIM) instrument. MAIN OUTCOME
      MEASURES: Development of a new or worsened pressure ulcer in patients during the
      rehabilitation stay compared to patients with no documented pressure ulcer or no
      worsened ulcer. RESULTS: Admission FIM total was strongly associated with
      development of a new or worsened pressure ulcer, P <.001 in analyses of all
      patients and for each of the 3 impairment-specific groups with the highest rate
      of ulcer development among spinal cord injury, orthopedic, and amputation cases.
      CMS comorbidity tier was also significantly associated with ulcers in all models.
      Other variables that entered one or more models included increased age, male
      gender, and use of a wheelchair. CONCLUSIONS: Admission FIM total and CMS
      comorbidity tier may be useful in the identification of patients at risk for
      development of new or worsened pressure ulcers in IRFs. Identification of
      pressure ulcer risk factors has important implications for individual plan-of
      care decisions as well as for resource provisions during the rehabilitation stay.

PMID- 25617705
TI  - An Appropriate Population for Acute Inpatient Rehabilitation? A Case Series of
      Three Patients With Advanced Heart Failure on Continuous Inotropic Support.
AB  - The number of individuals with heart failure and the treatment modalities
      available to manage heart failure are increasing. Continuous inotropic support is
      a treatment modality used in cases of severe heart failure. Although most
      patients initiated on continuous inotropic support are discharged home, those
      with greater functional compromise, comorbid conditions that cause disability, or
      other significant medical complexity may be referred to acute inpatient
      rehabilitation. The feasibility and benefits of acute inpatient rehabilitation in
      this population, however, has yet to be investigated. We report the functional
      progress and medical complications of 3 patients on continuous inotropic support
      who participated in acute inpatient rehabilitation. The patients demonstrated
      varying levels of success, highlighting a need for evidence-based, preadmission
      screening criteria for this population. 

PMID- 25617706
TI  - The test skeletal matrix of the black sea urchin Arbacia lixula.
AB  - In the field of biomineralization, the past decade has been marked by the
      increasing use of high throughput techniques, i.e. proteomics, for identifying in
      one shot the protein content of complex macromolecular mixtures extracted from
      mineralized tissues. Although crowned with success, this approach has been
      restricted so far to a limited set of key-organisms, such as the purple sea
      urchin Strongylocentrotus purpuratus, the pearl oyster or the abalone, leaving in
      the shadow non-model organisms. As a consequence, it is still unknown to what
      extent the calcifying repertoire varies, from group to group, at high (phylum,
      class), median (order, family) or low (genus, species) taxonomic rank. The
      present paper shows the first biochemical and proteomic characterization of the
      test matrix of the Mediterranean black sea urchin Arbacia lixula (Arbacioida).
      Our work suggests that the skeletal repertoire of A. lixula exhibits some
      similarities but also several differences with that of the few sea urchin species
      (S. purpuratus, Paracentrotus lividus), for which molecular data are already
      available. The differences may be attributable to the taxonomic position of the
      species considered: A. lixula belongs to an order - Arbacioida - that diverged
      more than one hundred million years ago from the Camarodonta, which includes the
      two species S. purpuratus and P. lividus. For the echinoid class, we suggest that
      large-scale proteomic screening should be performed in order to understand which
      molecular functions related to calcification are conserved and which ones have
      been co-opted for biomineralization in particular lineages. 

PMID- 25617707
TI  - Effect of rooibos extract (Aspalathus linearis) on lipid oxidation over time and
      the sensory analysis of blesbok (Damaliscus pygargus phillipsi) and springbok
      (Antidorcas marsupialis) droewors.
AB  - The study objective was to investigate the addition of rooibos extract (RBE) in
      blesbok and springbok droewors, a dried meat sausage with added beef fat, to
      improve oxidative stability. After a storage period of two weeks, inhibition of
      lipid oxidation showed to be successful with RBE 1.0% addition. No differences
      (P>0.05) in heme-iron results within the raw, dried or stored samples were seen.
      However, a positive correlation between lipid oxidation and heme-iron was noted.
      The fatty acid profiles suggest that after drying the decrease in polyunsaturated
      fats could be linked to the increase in lipid oxidation. Flavor and aroma
      differences between the varying RBE concentrations in the droewors were detected
      by the sensory panel. A droewors formulation using a combination of game meat and
      beef fat with the addition of RBE at a 1.0% concentration could be a successful
      addition to the processed meat market. 

PMID- 25617708
TI  - Application of the CIEMAT-NIST method to plastic scintillation microspheres.
AB  - An adaptation of the MICELLE2 code was used to apply the CIEMAT-NIST tracing
      method to the activity calculation for radioactive solutions of pure beta
      emitters of different energies using plastic scintillation microspheres (PSm) and
      (3)H as a tracing radionuclide. Particle quenching, very important in
      measurements with PSm, was computed with PENELOPE using geometries formed by a
      heterogeneous mixture of polystyrene microspheres and water. The results obtained
      with PENELOPE were adapted to be included in MICELLE2, which is capable of
      including the energy losses due to particle quenching in the computation of the
      detection efficiency. The activity calculation of (63)Ni, (14)C, (36)Cl and
      (90)Sr/(90)Y solutions was performed with deviations of 8.8%, 1.9%, 1.4% and
      2.1%, respectively. Of the different parameters evaluated, those with the
      greatest impact on the activity calculation are, in order of importance, the
      energy of the radionuclide, the degree of quenching of the sample and the packing
      fraction of the geometry used in the computation. 

PMID- 25617709
TI  - Measurements of the cross section for the (182)W(n,p)(182(m+g))Ta and
      (184)(n,p)(184)Ta reactions in the 14MeV energy range using the activation
      technique.
AB  - The cross section for the (182)W(n,p)(182(m+g))Ta and (184)W(n,p)(184)Ta
      reactions has been measured in the neutron energy range of 13.5-14.7MeV using the
      activation technique and a coaxial HPGe gamma-ray detector. In our experiment,
      the fast neutrons were produced by the T(d,n)(4)He reaction at the ZF-300-II
      Intense Neutron Generator at Lanzhou University. Natural wolfram foils of 99.9%
      purity were used as target materials. The neutron flux was determined using the
      monitor reaction (93)Nb(n,2n)(92m)Nb and the neutron energies were determined
      using the method of cross-section ratio measurements employing the
      (90)Zr(n,2n)(89)Zr to (93)Nb(n,2n)(92m)Nb reactions. The results of this work are
      compared with experimental data found in the literature and the estimates
      obtained from a published empirical formula based on the statistical model with Q
      value dependence and odd-even effects taken into consideration. 

PMID- 25617710
TI  - Interface behavior of Al2O3/Ti joints produced by liquid state bonding.
AB  - In this work we study brazing of Al2O3 to Ti with biocompatibility properties,
      using a Au-foil as joining element. Al2O3 was produced by sintering of powder at
      1550 degrees C. Al2O3 samples were coated with a 2 and 4MUm thick of Mo layer and
      then stacked with Ti. Al2O3-Mo/Au/Ti combinations were joined at 1100 degrees C
      in vacuum. Successful joining of Mo-Al2O3 to Ti was observed. Interface shows the
      formation of a homogeneous diffusion zone. Mo diffused inside Au forming a
      concentration line. Ti3Au and TiAu phases were observed. 

PMID- 25617711
TI  - Thermoresponsive polymer system based on poly(N-vinylcaprolactam) intended for
      local radiotherapy applications.
AB  - Brachytherapy represents effective local therapy of unresectable solid tumors
      with very few side effects. Radiolabeled thermoresponsive polymers offer almost
      noninvasive approach to brachytherapy applications. A radioiodinated, water
      soluble, thermosensitive poly(N-vinylcaprolactam) (PVCL) polymer was prepared
      using two approaches. The direct copolymerization with N-methacryloyl-l
      tyrosinamide, as well as end-capping of carboxy-terminated PVCL homopolymer with
      tyramine, were used. In both cases the product was successfully radiolabeled with
      (125)I. The obtained polymers demonstrate cloud-point temperature (TC) values in
      the range of 33-35 degrees C in all the studied solvent systems (water, PBS (pH
      7.4) and physiological saline solution). Above the cloud point temperature, the
      molecularly dissolved polymer is macroprecipitated from the solution. The TC
      values close to the human body temperature of this biocompatible poly(N
      vinylcaprolactam) polymer makes it a promising material intended for local
      therapy of solid tumors. 

PMID- 25617712
TI  - Attenuation correction for the collimated gamma ray assay of cylindrical samples.
AB  - The Hybrid Monte Carlo (HMC) method developed earlier for attenuation correction
      of non-collimated samples [Agarwal et al., 2008, Nucl. Instrum. Methods A 597,
      198], has been extended to the segmented gamma ray assay of cylindrical samples.
      The method has been validated both experimentally and theoretically. For
      experimental validation, the results of HMC calculation have been compared with
      the experimentally obtained attenuation correction factors. The HMC attenuation
      correction factors have also been compared with the results obtained from
      literature available near-field and far-field formulae at two sample-to-detector
      distances (10.3cm and 20.4cm). The method has been found to be valid at all
      sample-to-detector distances over a wide range of transmittance. On the other
      hand, the literature available near-field and far-field formulae have been found
      to work over a limited range of sample-to detector distances and transmittances.
      The HMC method has been further extended to circular collimated geometries where
      analytical formula for attenuation correction does not exist. 

PMID- 25617713
TI  - Intrinsic exercise capacity is related to differential monoaminergic activity in
      the rat forebrain.
AB  - Monoamines levels in central nervous system have been associated with exercise
      performance and fatigue. The present study investigated whether intrinsic
      exercise capacity is associated with differential activity of monoamines in the
      caudate-putamen (CPu) and accumbens (ACC) nucleus. Male Wistar rats were
      subjected to a progressive testing protocol. Based on the maximal time of
      exercise in the progressive testing protocol (TEPmax), the animals were divided
      into low-performance (LP), high-performance (HP), and standard-performance (SP)
      groups. After classification, eight animals in each group were chosen randomly
      and evaluated in two experimental situations: rest (n=8) or moderate exercise
      (ME) at 60% of maximal velocity (n=8). The CPu and ACC were dissected for
      analyses of monoamine levels. At rest, HP rats exhibited higher 3,4
      dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio and lower serotonin (5-HT)
      concentration compared other groups, and lower 5-hydroxyindoleacetic (5-HIAA)
      compared with the LP rats. The ME resulted in increased DOPAC/DA ratio in the CPu
      of all experimental groups. In both the CPu and ACC, ME increased 5-HIAA levels
      in SP and HP rats and 5-HIAA/5-HT ratio only in HP rats. Thus, our findings
      demonstrate that rats with natural intrinsic differences in performance to
      exercise exhibit alterations in dopaminergic and serotonergic systems at rest and
      after ME exercise until fatigue. 

PMID- 25617714
TI  - Genome-wide DNA methylation analysis in Graves' disease.
AB  - As an autoimmune disease, Graves' disease (GD) is associated with many genetic
      and environmental risk factors. Although the exact mechanism remains unclear,
      epigenetic determinants, such as DNA methylation, are thought to contribute to
      the pathogenesis of GD. Here, we for the first time reported the DNA methylation
      pattern in GD through a high-throughput analysis. In order to investigate genome
      wide DNA methylation profile of GD, methyl-DNA immunoprecipitation (MeDIP) and
      Nimblegen human DNA methylation 3 * 720 K promoter plus CpG island microarrays
      were used to identify differentially methylated regions (DMRs) from blood samples
      in GD patients. Quantitative methylation-specific PCR (qMSP) was used to validate
      the methylation state of candidate genes. Transcription level of each gene was
      estimated by quantitative real-time PCR (qRT-PCR). A total of 132 hypermethylated
      and 133 hypomethylated regions were identified in GD. The methylation of ICAM1 in
      GD patients and normal controls was significantly different (p<0.05). In the
      female group, significantly decreased methylation was observed in GD patients
      compared with normal controls (p<0.05). The transcription of ICAM1 at the mRNA
      level was significantly higher in GD patients compared with normal controls
      (p<0.05). Besides, the transcription of DNMT1 and MECP2 at the mRNA level was
      significantly decreased in GD patients compared with normal controls (p<0.05).
      Our findings revealed that the DNA methylation pattern in GD was distinct from
      that of controls. These results provided new molecular insights into the
      pathogenesis of GD.

PMID- 25617716
TI  - Functional histopathological markers of aldosterone producing adenoma and somatic
      KCNJ5 mutations.
AB  - The current pathological diagnosis of Aldosterone Producing Adenoma (APA) is
      limited to the description of nodules and/or hyperplasia in the resected adrenal
      gland, independent of their functional characteristics. The aim of our study was
      to characterize histopathological markers to confirm the presence and identify
      the sites of aldosterone production and to discriminate KCNJ5-related APA. We
      investigated 18 adrenals with APA and 15 with non-functioning adrenal
      incidentaloma (NFAI) for expression of Disabled-2 and GIRK4, two markers of zona
      glomerulosa (ZG), and 77 adrenals with APA with known mutational status for GIRK4
      expression. Two-thirds of APA and only one NFAI exhibited both GIRK4 and Disabled
      2 membrane staining, allowing to correctly classify 79% of adenomas. Remarkably,
      28/32 APA with KCNJ5 mutations exhibited lower GIRK4 expression in APA relative
      to peritumoral ZG. This was highly specific for KCNJ5 mutations, indicating that
      GIRK4 immunohistochemistry might be used for initial screening of the somatic
      mutation status.

PMID- 25617715
TI  - MicroRNAs-141 and 200a regulate the SVCT2 transporter in bone marrow stromal
      cells.
AB  - Vitamin C is a micro-nutrient which plays an important role in bone marrow
      stromal cell (BMSCs) differentiation to osteogenesis. This vitamin is transported
      into the BMSCs through the sodium dependent vitamin C transporter 2 (SVCT2). We
      previously reported that knockdown of the SVCT2 transporter decreases osteogenic
      differentiation. However, our understanding of the post-transcriptional
      regulatory mechanism of the SVCT2 transporter remains poor. MicroRNAs (miRNAs)
      are small non-coding RNAs that post-transcriptionally regulate the messenger RNAs
      of protein-coding genes. In this study, we aimed to investigate the impact of miR
      141 and miR-200a on SVCT2 expression. We found that mouse BMSCs expressed miR-141
      and miR-200a and repressed SVCT2 expression at the functional level by targeting
      the 3'-untranslated region of mRNA. We also found that miR-141 and miR-200a
      decreased osteogenic differentiation. Furthermore, miRNA inhibitors increased
      SVCT2 and osteogenic gene expression in BMSCs. Taken together, these results
      indicate that both miRNAs are novel regulators of the SVCT2 transporter and play
      an important role in the osteogenic differentiation of BMSCs. 

PMID- 25617717
TI  - The proteomic 2D-DIGE approach reveals the protein voltage-dependent anion
      channel 2 as a potential therapeutic target in epithelial thyroid tumours.
AB  - We investigated the role of VDAC2 in human epithelial thyroid tumours using
      proteomic 2D-DIGE analysis and qRT-PCR. We found a significant up-regulation of
      VDAC2 in thyroid tumours and in thyroid tumour cell lines (TPC-1 and CAL-62). We
      did not detect overexpression of VDAC2 in a normal thyroid cell line (Nthy-ori 3
      1). Silico analysis revealed that two proteins, BAK1 and BAX, had a strong
      relationship with VDAC2. BAK1 gene expression showed down-regulation in thyroid
      tumours (follicular and papillary tumours) and in TPC-1 and CAL-62 cell lines.
      Transient knockdown of VDAC2 in TPC-1 and CAL-62 promoted upregulation of the
      BAK1 gene and protein expression, and increased susceptibility to sorafenib
      treatment. Overexpression of the BAK1 gene in CAL-62 showed lower sorafenib
      sensitivity than VDAC2 knockdown cells. We propose the VDAC2 gene as a novel
      therapeutic target in these tumours. 

PMID- 25617718
TI  - SKIP Confers Osmotic Tolerance during Salt Stress by Controlling Alternative Gene
      Splicing in Arabidopsis.
AB  - Deciphering the mechanisms underlying plant responses to abiotic stress is key
      for improving plant stress resistance. Much is known about the regulation of gene
      expression in response to salt stress at the transcriptional level; however,
      little is known about this process at the posttranscriptional level. Recently, we
      demonstrated that SKIP is a component of spliceosome that interacts with clock
      gene pre-mRNAs and is essential for regulating their alternative splicing and
      mRNA maturation. In this study, we found that skip-1 plants are hypersensitive to
      both salt and osmotic stresses, and that SKIP is required for the alternative
      splicing and mRNA maturation of several salt-tolerance genes, including NHX1,
      CBL1, P5CS1, RCI2A, and PAT10. A genome-wide analysis revealed that SKIP mediates
      the alternative splicing of many genes under salt-stress conditions, and that
      most of the alternative splicing events in skip-1 involve intron retention and
      can generate a premature termination codon in the transcribed mRNA. SKIP also
      controls alternative splicing by modulating the recognition or cleavage of 5' and
      3' splice donor and acceptor sites under salt-stress conditions. Therefore, this
      study addresses the fundamental question of how the mRNA splicing machinery in
      plants contributes to salt-stress responses at the posttranscriptional level, and
      provides a link between alternative splicing and salt tolerance. 

PMID- 25617719
TI  - The miR156/SPL Module, a Regulatory Hub and Versatile Toolbox, Gears up Crops for
      Enhanced Agronomic Traits.
AB  - In the past two decades, members of the SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE
      (SPL) family of transcription factors, first identified in Antirrhinum majus,
      have emerged as pivotal regulators of diverse biological processes in plants,
      including the timing of vegetative and reproductive phase change, leaf
      development, tillering/branching, plastochron, panicle/tassel architecture, fruit
      ripening, fertility, and response to stresses. Transcripts of a subset of SPLs
      are targeted for cleavage and/or translational repression by microRNA156s
      (miR156s). The levels of miR156s are regulated by both endogenous developmental
      cues and various external stimuli. Accumulating evidence shows that the
      regulatory circuit around the miR156/SPL module is highly conserved among
      phylogenetically distinct plant species, and plays important roles in regulating
      plant fitness, biomass, and yield. With the expanding knowledge and a mechanistic
      understanding of their roles and regulatory relationship, we can now harness the
      miR156/SPL module as a plethora of tools to genetically manipulate crops for
      optimal parameters in growth and development, and ultimately to maximize yield by
      intelligent design of crops.

PMID- 25617720
TI  - Rice OsFLS2-Mediated Perception of Bacterial Flagellins Is Evaded by Xanthomonas
      oryzae pvs. oryzae and oryzicola.
AB  - Bacterial flagellins are often recognized by the receptor kinase FLAGELLIN
      SENSITIVE2 (FLS2) and activate MAMP-triggered immunity in dicotyledonous plants.
      However, the capacity of monocotyledonous rice to recognize flagellins of key
      rice pathogens and its biological relevance remain poorly understood. We
      demonstrate that ectopically expressed OsFLS2 in Arabidopsis senses the eliciting
      flg22 peptide and in vitro purified Acidovorax avenae (Aa) flagellin in an
      expression level-dependent manner, but does not recognize purified flagellins or
      derivative flg22(Xo) peptides of Xanthomonas oryzae pvs. oryzae (Xoo) and
      oryzicola (Xoc). Consistently, the flg22 peptide and purified Aa flagellin, but
      not Xoo/Xoc flagellins, induce various immune responses such as defense gene
      induction and MAPK activation in rice. Perception of flagellin by rice does
      induce strong resistance to Xoo infection, as shown after pre-treatment of rice
      leaves with Aa flagellin. OsFLS2 was found to differ from AtFLS2 in its
      perception specificities or sensitivities to different flg22 sequences. In
      addition, post-translational modification of Xoc flagellin was altered by
      deletion of glycosyltransferase-encoding rbfC, but this had little effect on Xoc
      motility and rpfC mutation did not detectably reduce Xoc virulence on rice.
      Deletion of flagellin-encoding fliC from Xoo/Xoc blocked swimming motility but
      also did not significantly alter Xoo/Xoc virulence. These results suggest that
      Xoo/Xoc carry flg22-region amino acid changes that allow motility while evading
      the ancient flagellin detection system in rice, which retains recognition
      capacity for other bacterial pathogens. 

PMID- 25617721
TI  - Evidence for intermediate mesoderm and kidney progenitor cell specification by
      Pax2 and PTIP dependent mechanisms.
AB  - Activation of the Pax2 gene marks the intermediate mesoderm shortly after
      gastrulation, as the mesoderm becomes compartmentalized into paraxial,
      intermediate, and lateral plate. Using an EGFP knock-in allele of Pax2 to
      identify and sort cells of the intermediate mesodermal lineage, we compared gene
      expression patterns in EGFP positive cells that were heterozygous or homozygous
      null for Pax2. Thus, we identified critical regulators of intermediate mesoderm
      and kidney development whose expression depended on Pax2 function. In cell
      culture models, Pax2 is thought to recruit epigenetic modifying complex to
      imprint activating histone methylation marks through interactions with the
      adaptor protein PTIP. In kidney organ culture, conditional PTIP deletion showed
      that many Pax2 target genes, which were activated early in renal progenitor
      cells, remained on once activated, whereas Pax2 target genes expressed later in
      kidney development were unable to be fully activated without PTIP. In Pax2
      mutants, we also identified a set of genes whose expression was up-regulated in
      EGFP positive cells and whose expression was consistent with a cell fate
      transformation to paraxial mesoderm and its derivatives. These data provide
      evidence that Pax2 specifies the intermediate mesoderm and renal epithelial cells
      through epigenetic mechanisms and in part by repressing paraxial mesodermal fate.

PMID- 25617723
TI  - Sustained drug release by contact lenses for glaucoma treatment-a review.
AB  - In the context of ocular pharmacology, there is a growing need for innovative
      delivery platforms for a convenient and sustained drug release into the eye,
      especially for chronic diseases that require the adoption of a strict
      insurmountable treatment regimen for a large part of the affected population, as
      in the case of glaucoma. Due to the large residence time of the contact lenses in
      the eye, its use for sustained drug delivery is quite promising. However, and
      despite the numerous therapeutic advantages arising from its use, the low
      affinity shown by most ophthalmic drugs for conventional contact lenses hinders
      the practical application of this technology. In this paper we elaborated a
      review of the various methods exploited so far to improve the contact lenses'
      characteristics as mechanisms for controlled and prolonged drug release for
      topical treatment of ocular diseases, with particular emphasis on the treatment
      of glaucoma. 

PMID- 25617722
TI  - RhoGAP68F controls transport of adhesion proteins in Rab4 endosomes to modulate
      epithelial morphogenesis of Drosophila leg discs.
AB  - Elongation and invagination of epithelial tissues are fundamental developmental
      processes that contribute to the morphogenesis of embryonic and adult structures
      and are dependent on coordinated remodeling of cell-cell contacts. The
      morphogenesis of Drosophila leg imaginal discs depends on extensive remodeling of
      cell contacts and thus provides a useful system with which to investigate the
      underlying mechanisms. The small Rho GTPase regulator RhoGAP68F has been
      previously implicated in leg morphogenesis. It consists of on an N-terminal Sec14
      domain and a C-terminal GAP domain. Here we examined the molecular function and
      role of RhoGAP68F in epithelial remodeling. We find that depletion of RhoGAP68F
      impairs epithelial remodeling from a pseudostratified to simple, while
      overexpression of RhoGAP68F causes tears of lateral cell-cell contacts and thus
      impairs epithelial integrity. We show that the RhoGAP68F protein localizes to
      Rab4 recycling endosomes and forms a complex with the Rab4 protein. The Sec14
      domain is sufficient for localizing to Rab4 endosomes, while the activity of the
      GAP domain is dispensable. RhoGAP68F, in turn, inhibits the scission and movement
      of Rab4 endosomes involved in transport the adhesion proteins Fasciclin3 and E
      cadherin back to cell-cell contacts. Expression of RhoGAP68F is upregulated
      during prepupal development suggesting that RhoGAP68F decreases the transport of
      key adhesion proteins to the cell surface during this developmental stage to
      decrease the strength of adhesive cell-cell contacts and thereby facilitate
      epithelial remodeling and leg morphogenesis. 

PMID- 25617724
TI  - Lipid prodrug nanocarriers in cancer therapy.
AB  - Application of nanotechnology in the medical field (i.e., nanomedicine) plays an
      important role in the development of novel drug delivery methods. Nanoscale drug
      delivery systems can indeed be customized with specific functionalities in order
      to improve the efficacy of the treatments. However, despite the progresses of the
      last decades, nanomedicines still face important obstacles related to: (i) the
      physico-chemical properties of the drug moieties which may reduce the total
      amount of loaded drug; (ii) the rapid and uncontrolled release (i.e., burst
      release) of the encapsulated drug after administration and (iii) the instability
      of the drug in biological media where a fast transformation into inactive
      metabolites can occur. As an alternative strategy to alleviate these drawbacks,
      the prodrug approach has found wide application. The covalent modification of a
      drug molecule into an inactive precursor from which the drug will be freed after
      administration offers several benefits such as: (i) a sustained drug release
      (mediated by chemical or enzymatic hydrolysis of the linkage between the drug
      moiety and its promoiety); (ii) an increase of the drug chemical stability and
      solubility and, (iii) a reduced toxicity before the metabolization occurs. Lipids
      have been widely used as building blocks for the design of various prodrugs.
      Interestingly enough, these lipid-derivatized drugs can be delivered through a
      nanoparticulate form due to their ability to self-assemble and/or to be
      incorporated into lipid/polymer matrices. Among the several prodrugs developed so
      far, this review will focus on the main achievements in the field of lipid-based
      prodrug nanocarriers designed to improve the efficacy of anticancer drugs.
      Gemcitabine (Pubchem CID: 60750); 5-fluorouracil (Pubchem CID: 3385); Doxorubicin
      (Pubchem CID: 31703); Docetaxel (Pubchem CID: 148124); Methotrexate (Pubchem CID:
      126941); Paclitaxel (Pubchem CID: 36314).

PMID- 25617725
TI  - Bispecific single-chain diabody-immunoliposomes targeting endoglin (CD105) and
      fibroblast activation protein (FAP) simultaneously.
AB  - Liposomes are well-established drug delivery systems with cancer chemotherapy as
      main focus. To increase the cellular drug delivery, liposomes can be endowed with
      ligands, e.g. recombinant antibody fragments, which ensure specific cell
      interaction. Multispecific immunoliposomes can be prepared to improve the
      liposome to cell interaction by targeting multiple different targets at the same
      time, for instance by coupling two or more different ligands to the liposomal
      surface, resulting in a synergistic or additive increase in binding. An
      alternative approach is the use of bispecific ligands to address at least two
      different targets. For this purpose we cloned a single-chain diabody fragment
      (scDb'), a bispecific molecule targeting two antigens, endoglin (CD105) and
      fibroblast activation protein (FAP), expressed on cells of the tumor
      microenvironment. As model cell system, a human fibrosarcoma cell line was used
      expressing endoglin and FAP simultaneously. Monospecific immunoliposomes directed
      either against endoglin or FAP were compared in vitro for cell binding and
      cytotoxic activity with bispecific dual-targeted scFv'-IL (bispecific
      scFv'FAP/CD105-IL) and bispecific single-chain diabody'-IL (scDb'CD105/FAP-IL)
      targeting endoglin and FAP simultaneously. In the underlying study, bispecific
      scFv'FAP/CD105-IL interacted stronger with cells expressing FAP and endoglin
      (both targets simultaneously) compared to the monospecific immunoliposomes.
      Furthermore, bispecific scDb'-immunoliposomes increased the cell interaction
      massively and showed enhanced cytotoxicity against target cells using doxorubicin
      loaded immunoliposomes. The use of recombinant bispecific ligands as scDb'
      molecules facilitates the generation of bispecific immunoliposomes by using the
      established post-insertion technique, enabling an extension of the ligand
      specificity spectrum via genetic modification. 

PMID- 25617726
TI  - Gut microbial and short-chain fatty acid profiles in adults with chronic
      constipation before and after treatment with lubiprostone.
AB  - Identifying specific gut microorganisms associated with chronic constipation may
      be useful for diagnostic and therapeutic purposes. The objective of this study
      was to evaluate whether or not the gut microbial community of constipated
      subjects had specific microbial signatures and to assess the effects of
      lubiprostone treatment on the gut microbial community. Stool diaries, breath H2
      and CH4 levels, and stool samples were collected from ten healthy subjects and
      nine patients meeting the Rome III criteria for chronic functional constipation.
      Constipated subjects received lubiprostone for four weeks, during which stool
      diaries were maintained. Stool samples were evaluated for gut microbial
      communities using pyrosequencing and quantitative real-time PCR (qPCR) targeting
      16S-rRNA gene, along with concentrations of short-chain fatty acids (SCFAs) using
      high-performance liquid chromatography. Prior to treatment, gut microbial
      profiles were similar between constipated subjects and healthy subjects, while
      iso-butyrate levels were significantly higher in constipated subjects compared
      with healthy subjects. Despite increases in stool frequency and improvements in
      consistency after lubiprostone treatment, gut microbial profiles and community
      diversity after treatment showed no significant change compared to before
      treatment. While we did not observe a significant difference in either breath
      methane or archaeal abundance between the stool samples of healthy and
      constipated subjects, we confirmed a strong correlation between archaeal
      abundance measured by qPCR and the amount of methane gas exhaled in the fasting
      breath. Butyrate levels, however, were significantly higher in the stool samples
      of constipated subjects after lubiprostone treatment, suggesting that
      lubiprostone treatment had an effect on the net accumulation of SCFAs in the gut.
      In conclusion, lubiprostone treatment improved constipation symptoms and
      increased levels of butyrate without substantial modification of the gut
      microbial structure. 

PMID- 25617727
TI  - Cystic adenomyosis spreading into subserosal-peduncolated myoma: How to explain
      it?
AB  - INTRODUCTION: Cystic adenomyosis is a rare variant of adenomyosis characterized
      by well- circumscribed cavitated endometrial gland and stroma located within the
      myometrium. The cysts usually measure>=1cm in diameter, contain a "chocolate
      colored" fluid and do not open into the overlaying endometrium. CASE
      PRESENTATION: We present a case of a peduncolated-subserosal cystic adenomyoma,
      namely cystic adenomyosis, correlated with pelvic MR imaging, laparoscopic
      surgery technique and histopathology findings. CONCLUSIONS: In this case, the
      peculiar growth pattern of cystic adenomyosis in a myoma represents a singular
      condition rarely reported in the medical literature. We therefore support the
      pathogenetic theory that the disease might have been caused by direct
      proliferation of endometrial cells within a peduncolated- subserosal myoma.

PMID- 25617728
TI  - Saved from a fatal flight: A ruptured splenic artery aneurysm in a pregnant
      woman.
AB  - INTRODUCTION: The reported prevalence of a SAA varies between 0.01 and 10.4% [1],
      and since SAAs often remain asymptomatic, the true prevalence is uncertain. The
      reported SAAs occur more frequently in younger patients, with 58% diagnosed in
      women of childbearing age; 95% of these are diagnosed during pregnancy.
      PRESENTATION OF CASE: A 26-year-old woman, thirty-one weeks pregnant, was about
      to board an airplane for a three hour flight from the Netherlands to Turkey. Just
      before entering the plane, she suddenly felt a severe abdominal pain. Ultrasound
      guided aspiration of the abdominal fluid showed blood and supported the decision
      to perform urgent laparotomy. A caesarean section was performed. After further
      inspection a ruptured SAA was encountered. The splenic artery was ligated
      proximally and distally to the rupture in order to stop the bleeding. As the
      hilar localization of the aneurysm interfered with a primary vascular
      reconstruction, a splenectomy was performed. The mother and baby survived.
      DISCUSSION: Although rupture of a SAA is rare, its consequences can be
      devastating for both mother and child. The literature shows a higher incidence of
      ruptured SAA in pregnant women, although there is a difficulty in recognizing
      hemodynamic instability in pregnancy due to the increase in circulating volume.
      CONCLUSION: In case of pregnant women with acute abdomen and hypovolemia,
      emergency physicians, surgeons, anesthesiologists, and gynecologists should be
      aware of the possibility of a ruptured SAA, apart from more common causes like
      placental abruption, placenta percreta, or uterine rupture. Early recognition and
      prompt multidisciplinary treatment might save the life of mother and child.

PMID- 25617729
TI  - Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and
      ER stress activation in a type 2 diabetes rat model.
AB  - Recent studies demonstrate an important role of protein kinase D (PKD) in the
      cardiovascular system. However, the potential role of PKD in the pathogenesis of
      diabetic cardiomyopathy (DCM) remains unclear. Irbesartan has beneficial effects
      against diabetes-induced heart damage, while the mechanisms were still poorly
      understood. Our present study was designed to investigate the effects of
      irbesartan in DCM and whether the cardioprotective effects of irbesartan were
      mediated by PKD and endoplasmic reticulum (ER) stress. We induced the type 2
      diabetic rat model by high fat diet and low dose streptozotocin injection. The
      characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography
      and histopathology. 8-weeks administration of irbesartan (15, 30 and 45mg/kg/day)
      was used to evaluate the effect irbesartan in DCM. Diabetic rats revealed severe
      metabolic abnormalities, left ventricular dysfunction, myocardial fibrosis and
      apoptosis. PKD and ER stress were excessive activated in the myocardium of
      diabetic rats. Furthermore, cardiac fibrosis, apoptosis, diastolic dysfunction
      and ER stress were all significantly related to PKD activation in diabetic rats.
      Irbesartan treatment attenuated the activation of PKD and ER stress, which
      paralleled its cardioprotective effects. Our study suggests that irbesartan could
      ameliorate cardiac remodeling and dysfunction in type 2 diabetes, and these
      beneficial effects were associated with its ability to suppress the activation of
      PKD and ER stress. 

PMID- 25617730
TI  - The effects of JM-20 on the glutamatergic system in synaptic vesicles,
      synaptosomes and neural cells cultured from rat brain.
AB  - JM-20 (3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido[2,3
      b][1,5]benzodiazepine) is a novel benzodiazepine dihydropyridine hybrid molecule,
      which has been shown to be a neuroprotective agent in brain disorders involving
      glutamate receptors. However, the effect of JM-20 on the functionality of the
      glutamatergic system has not been investigated. In this study, by using different
      in vitro preparations, we investigated the effects of JM-20 on (i) rat brain
      synaptic vesicles (L-[(3)H]-glutamate uptake, proton gradient built-up and
      bafilomycin-sensitive H(+)-ATPase activity), (ii) rat brain synaptosomes
      (glutamate release) and (iii) primary cultures of rat cortical neurons,
      astrocytes and astrocyte-neuron co-cultures (L-[(3)H]-glutamate uptake and
      glutamate release). We observed here that JM-20 impairs H(+)-ATPase activity and
      consequently reduces vesicular glutamate uptake. This molecule also inhibits
      glutamate release from brain synaptosomes and markedly increases glutamate uptake
      in astrocytes alone, and co-cultured neurons and astrocytes. The impairment of
      vesicular glutamate uptake by inhibition of the H(+)-ATPase caused by JM-20 could
      decrease the amount of the transmitter stored in synaptic vesicles, increase the
      cytosolic levels of glutamate, and will thus down-regulate neurotransmitter
      release. Together, these results contribute to explain the anti-excitotoxic
      effect of JM-20 and its strong neuroprotective effect observed in different in
      vitro and in vivo models of brain ischemia. 

PMID- 25617731
TI  - Integrated analysis of microRNA and mRNA expression profiles in the left atrium
      of patients with nonvalvular paroxysmal atrial fibrillation: Role of miR-146b-5p
      in atrial fibrosis.
AB  - BACKGROUND: Studies have reported that the integrated analysis of microRNA
      (miRNA)-messenger RNA (mRNA) expression is valuable in exploring gene regulation
      systemically. OBJECTIVES: The objectives of this study were to identify miRNAs
      and genes involved in atrial fibrillation and to explore the mechanisms
      underlying atrial fibrosis. METHODS: We used microarrays to compare the
      differences in both miRNA and mRNA expression profiles in the left atrial
      appendage of patients with nonvalvular paroxysmal atrial fibrillation and healthy
      controls. Furthermore, the quantitative real-time polymerase chain reaction was
      used to confirm the reliability of the microarray data, prediction of the adopted
      databases, and Ingenuity Pathway Analysis of miRNA-mRNA expression in order to
      identify the miRNA target genes, examine the functions and pathways in which the
      target genes are involved, and construct an miRNA-target gene regulatory network.
      We further investigated the roles of miRNA-146b-5p in the mechanisms of atrial
      fibrosis. RESULTS: We identified 10 differentially expressed miRNAs and 624
      differentially expressed mRNAs, among which only 1 miRNA-target gene pair miR
      146b-5p and tissue inhibitor of metalloproteinase 4 (TIMP-4) were constructed.
      The validated results revealed that miR-146b-5p, matrix metallopeptidase 9, and
      collagen content were upregulated whereas TIMP-4 was downregulated in patients
      with atrial fibrillation. After the transfection of miR-146b-5p into cardiac
      fibroblasts, TIMP-4 expression was markedly reduced and collagen content was
      increased. Moreover, luciferase results confirmed that TIMP-4 was a target of miR
      146b-5p. CONCLUSION: The identified miRNA and mRNA may represent a potentially
      novel molecular regulatory network, which may provide a better understanding of
      the molecular basis of remodeling in atrial fibrillation. miR-146b-5p probably
      acts as an intracellular mediator in the maladaptive remodeling in atrial
      fibrosis in atrial fibrillation.

PMID- 25617732
TI  - Can microRNA profiling in maternal blood identify women at risk for preterm
      birth?
AB  - OBJECTIVE: MicroRNAs (miRNAs), which are highly conserved single-stranded
      noncoding RNAs that play a crucial role in gene regulation, have now been
      identified as important players in many diseases states. MiRNAs have also been
      demonstrated to be reliable and useful biomarkers to identify those women who are
      at risk for specific adverse outcomes. The objective of this study was to
      determine whether miRNA profiles in maternal blood are different in women who are
      destined to have a preterm, compared with a term, birth. STUDY DESIGN: A nested
      case-control study was performed with maternal serum that was collected as part
      of a larger prospective cohort. MiRNA expression profiles in maternal serum were
      compared between women who ultimately had a preterm birth (n = 40) compared with
      term birth (n = 40). MiRNA expression profiles were created with the use of the
      Affymetrix GeneChip miRNA Array. The data were analyzed with the significance of
      analysis of microarrays and principle components analyses. A false discovery rate
      of 20% was used to determine the most differentially expressed miRNAs. RESULTS:
      Of the 5640 miRNAs that were analyzed on the array, 4 miRNAs were significantly
      different between cases and control subjects. Two of the 4 miRNAs were mature
      miRNAs. The fold difference in expression was <2 for all 4 miRNAs. CONCLUSION:
      MiRNA profiles in maternal blood were not significantly different in women who
      were destined to have a preterm, compared with a term, birth. MiRNAs in maternal
      blood are unlikely to become clinically useful biomarkers for the prediction of
      preterm birth.

PMID- 25617733
TI  - Correlation between viral loads performed at 34-36 weeks and in the immediate
      postpartum period in HIV-infected pregnant women using HAART.

PMID- 25617734
TI  - A novel Candida glabrata cell wall associated serine protease.
AB  - We set out to identify the Candida glabrata cell wall attached proteases which
      may play a role as virulence factors in candidosis, particularly in the
      immunocompromized host. We studied a clinical C. glabrata strain T-1639, which
      was isolated from a patient from the Helsinki University Central Hospital. With
      non-reducing 2-D electrophoresis using parallel fluorogenic gels and mass
      spectrometry we identified a novel appr. 25 kDa (192 aa in length) cell wall
      located protease with an estimated pI of 7.6. The LC-MS/MS peptides matched with
      the ORF of predicted C. glabrata CBS138 cell wall protein Cwp1.2p/pI 7.7/212 aa
      (http://cbi.labri.fr/Genolevures/[NCBI access 49525604, UniProt access Q6FTZ7]),
      which is an ortholog to Saccharomyces cerevisiae cell wall protein Cwp1p (UniProt
      access P28319). The novel serine protease was released by beta-1,3-glucanase
      treatment from the cell wall. In contrast to previous predictions this protease
      has an enzymatic function instead of being merely a structural cell wall protein.
      The protease showed gelatinolytic activity and was inhibited by PMSF, a known
      serine protease inhibitor. Further characterization of the protease may give
      insight to its role in infections caused by C. glabrata and possibly aid in the
      development of new kinds of antifungal drugs.

PMID- 25617735
TI  - Inhibition of STAT3/cyclinD1 pathway promotes chemotherapeutic sensitivity of
      colorectal caner.
AB  - BACKGROUND: Chemotherapeutic resistance indicated the poor prognosis of
      colorectal cancer. OBJECTIVE: Our study aimed to investigate the role of
      STAT3/cyclinD1 pathway in the chemotherapeutic resistance of colorectal cancer.
      METHODS: We firstly measured the expression of cyclinD1 in the colorectal cancer
      tissues using immunohistochemistry in tissue microarray. Then cell viability and
      apoptosis were investigated in the HT-29 cell lines dealing with recombinant
      lentivirus and shRNA to increase or decrease cyclinD1 expression. Furthermore,
      luciferase and ChIP assays were applied to investigate whether STAT3 regulated
      cyclinD1 expression by binding to its promoter. Finally, we determined whether
      inhibition of STAT3 could decrease cyclinD1 and increase the chemotherapy
      sensitivity. RESULTS: CyclinD1 expression was significantly increased in the
      cancer cells and high level of cyclinD1 indicated the poor prognosis. Inhibition
      of cyclinD1 decreased the cell viability assessed by MTT and increased rate of
      apoptosis when exposed to 5-FU treatment while overexpression of cyclinD1 showed
      the reverse effect. ChIP assay showed that STAT3 directly bind to cyclinD1
      promoter. Subclone of full promoter of cyclinD1 into pGL4 increased the
      luciferase activity while delete or mutation of any of STAT3 binding sites
      resulted in reductions of luciferase activity. Inhibition of STAT3 decreased
      cyclinD1 expression to decrease the cell viability and increase rate of apoptosis
      when exposed to 5-FU treatment. CONCLUSIONS: Inhibition of STAT3/cyclinD1 pathway
      increased the sensitivity of colorectal cancer cell to chemotherapy.

PMID- 25617737
TI  - Role of omega-3 PUFA-derived mediators, the protectins, in influenza virus
      infection.
AB  - Influenza A viruses are the causative agents of seasonal and pandemic infections.
      Influenza strains have recently emerged that show resistance to anti-viral drugs.
      Moreover, therapies in critically ill patients with severe influenza are limited,
      with the current anti-viral drugs showing disappointing results even in the
      absence of obvious viral resistance. Given the high mortality associated with
      avian H5N1 or H7N9 infections and the risk of pandemic potentials, effective
      drugs are needed for the treatment of severe influenza. A virus-host interaction
      is a multidimensional host response, in which not only genes and protein but also
      metabolites are up- or down-regulated, and cellular pathways and networks
      implicated in the viral pathogenesis are perturbed. Thus, it seems an attractive
      strategy to overcome influenza by targeting host metabolites and/or metabolic
      pathways involved in viral pathogenesis. Using lipidomics and lipid libraries
      screening, potectin D1 isomer (PDX) derived from the 15-lipoxygenase product 17S
      H(p)DHA and/or 17HDHA precursor, has recently been identified, which suppresses
      influenza virus replication by inhibiting the nuclear export of viral mRNA rather
      than regulating resolution of inflammation. Contribution of the protectins to
      control influenza virus replication and their therapeutic potentials are reviewed
      here. This article is part of a Special Issue entitled "Oxygenated metabolism of
      PUFA: analysis and biological relevance". 

PMID- 25617738
TI  - Extra-hepatic metabolism of 7-ketocholesterol occurs by esterification to fatty
      acids via cPLA2alpha and SOAT1 followed by selective efflux to HDL.
AB  - Accumulation of 7-ketocholesterol (7KCh) in tissues has been previously
      associated with various chronic aging diseases. Orally ingested 7KCh is readily
      metabolized by the liver and does not pose a toxicity threat. However, 7KCh
      formed in situ, usually associated with lipoprotein deposits, can adversely
      affect surrounding tissues by causing inflammation and cytotoxicity. In this
      study we have investigated various mechanisms for extra-hepatic metabolism of
      7KCh (e.g. hydroxylation, sulfation) and found only esterification to fatty
      acids. The esterification of 7KCh to fatty acids involves the combined action of
      cytosolic phospholipase A2 alpha (cPLA2alpha) and sterol O-acyltransferase
      (SOAT1). Inhibition of either one of these enzymes ablates 7KCh-fatty acid ester
      (7KFAE) formation. The 7KFAEs are not toxic and do not induce inflammatory
      responses. However, they can be unstable and re-release 7KCh. The higher the
      degree of unsaturation, the more unstable the 7KFAE (e.g.
      18:0>18:1>18:2>18:3?20:4). Biochemical inhibition and siRNA knockdown of SOAT1
      and cPLA2alpha ablated the 7KFAE synthesis in cultured ARPE19 cells, but had
      little effect on the 7KCh-induced inflammatory response. Overexpression of SOAT1
      reduced the 7KCh-induced inflammatory response and provided some protection from
      cell death. This effect is likely due to the increased conversion of 7KCh to
      7KFAEs, which reduced the intracellular 7KCh levels. Addition of HDL selectively
      increased the efflux of 7KFAEs and enhanced the effect of SOAT1 overexpression.
      Our data suggests an additional function for HDL in aiding extra-hepatic tissues
      to eliminate 7KCh by returning 7KFAEs to the liver for bile acid formation. 

PMID- 25617739
TI  - Effective and mild method for converting 3beta-hydroxysteroids to 3-keto steroids
      via DDQ/TEMPO.
AB  - A mild and efficient oxidation of 3beta-hydroxysteroids to the corresponding 3
      keto steroids can be carried out at room temperature, using DDQ in the presence
      of catalytic TEMPO. Oxidation of saturated 3beta-hydroxysteroids gave the
      corresponding ketones in excellent yield. The 5-unsaturated 3beta-hydroxysteroids
      are oxidized selectively to 4-en-3-one or 4,6-diene-3-one derivatives according
      to the amount of DDQ in reaction. This is a good method for the synthesis of 4,6
      diene-3-one from the corresponding 3beta-hydroxy-5-ene steroids. Meanwhile,
      configurations of the oxidation compounds 2a, 2b, 3b, 2c, 2f and 2g were
      identified by X-ray diffraction. A possible mechanism is presented and discussed.

PMID- 25617736
TI  - PIP kinases define PI4,5P2signaling specificity by association with effectors.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is an essential lipid messenger
      with roles in all eukaryotes and most aspects of human physiology. By controlling
      the targeting and activity of its effectors, PI4,5P2modulates processes, such as
      cell migration, vesicular trafficking, cellular morphogenesis, signaling and gene
      expression. In cells, PI4,5P2has a much higher concentration than other
      phosphoinositide species and its total content is largely unchanged in response
      to extracellular stimuli. The discovery of a vast array of PI4,5P2 binding
      proteins is consistent with data showing that the majority of cellular PI4,5P2is
      sequestered. This supports a mechanism where PI4,5P2functions as a localized and
      highly specific messenger. Further support of this mechanism comes from the de
      novo synthesis of PI4,5P2which is often linked with PIP kinase interaction with
      PI4,5P2effectors and is a mechanism to define specificity of PI4,5P2signaling.
      The association of PI4,5P2-generating enzymes with PI4,5P2effectors regulate
      effector function both temporally and spatially in cells. In this review, the
      PI4,5P2effectors whose functions are tightly regulated by associations with
      PI4,5P2-generating enzymes will be discussed. This article is part of a Special
      Issue entitled Phosphoinositides.

PMID- 25617740
TI  - Measurement of estradiol, estrone, and testosterone in postmenopausal human serum
      by isotope dilution liquid chromatography tandem mass spectrometry without
      derivatization.
AB  - BACKGROUND: A high-throughput, sensitive, specific, mass spectrometry-based
      method for quantitating estrone (E1), estradiol (E2), and testosterone (T) in
      postmenopausal human serum has been developed for clinical research. The method
      consumes 100MUl human serum for each measurement (triplicates consume 300MUl) and
      does not require derivatization. We adapted a commercially available 96-well
      plate for sample preparation, extraction, and introduction into the mass
      spectrometer on a single platform. METHODS: Steroid extraction from serum samples
      and mass spectrometer operational parameters were optimized for analysis of
      estradiol and subsequently applied to other analytes. In addition to determining
      the limit of detection (LOD) and limit of quantitation (LOQ) from standard
      curves, a serum LOQ (sLOQ) was determined by addition of known steroid quantities
      to serum samples. Mass spectrometric method quantitative data were compared to
      results using a state-of-the-art ELISA (enzyme-linked immunosorbent assay) using
      stored serum samples from menopausal women. RESULTS: The LOD, LOQ, sLOQ was
      (0.1pg, 0.3pg, 1pg/ml) for estrone, (0.3pg, 1pg, 3pg/ml) for estradiol, and
      (0.3pg, 1pg, 30pg/ml) for testosterone, respectively. Mass spectrometry
      accurately determined concentrations of E2 that could not be quantified by
      immunochemical methods. E1 concentrations measured by mass spectrometry were in
      all cases significantly lower than the ELISA measurements, suggesting
      immunoreactive contaminants in serum may interfere with ELISA. The testosterone
      measurements broadly agreed with each other in that both techniques could
      differentiate between low, medium and high serum levels. CONCLUSIONS: We have
      developed and validated a scalable, sensitive assay for trace quantitation of E1,
      E2 and T in human serum samples in a single assay using sample preparation method
      and stable isotope dilution mass spectrometry.

PMID- 25617741
TI  - Development and validation of liquid chromatography-tandem mass spectrometry
      method for simultaneous determination of six steroidal saponins in rat plasma and
      its application to a pharmacokinetics study.
AB  - A specific and reliable liquid chromatography-electrospray ionization-tandem mass
      spectrometry method was developed for the simultaneous determination of
      timosaponin H1 (TH1), timosaponin E1 (TE1), timosaponin E (TE), timosaponin B-II
      (TB-II), timosaponin B-III (TB-III) and anemarrhenasaponin I (AS-I) in rat
      plasma. After addition of internal standard (IS) ginsenoside Rh1, plasma samples
      were pretreated by protein precipitation with acetonitrile. Chromatographic
      separation was performed on a reverse phase ACQUITYTM BEH C18 column (100mm*2.1mm
      i.d., 1.7MUm) using a gradient mobile phase system of acetonitrile-water
      containing 0.05% formic acid and 5mM ammonium formate. The triple quadruple mass
      spectrometer was set in negative electrospray ionization mode and multiple
      reaction monitoring (MRM) was used for six steroidal saponins quantification. The
      precursors to produce ion transitions monitored for TH1, TE1, TE, TB-II, TB-III,
      AS-I and IS were m/z 1211.5>1079.6, 935.5>773.4, 935.4>773.5, 919.6>757.4,
      901.5>739.3, 757.4>595.3 and 637.3>475.3, respectively. The method validation was
      conducted over the curve range of 0.5-400ng/mL for the six saponins. The intra-
      and inter-day precisions (RSD%) were less than 9.4% and the average extraction
      recoveries ranged from 82.5% to 97.8% for each analyte. Six steroidal saponins
      were proved to be stable during sample storage, preparation and analytical
      procedures. The validated method was successfully applied for the first time to
      determine the concentrations of six main steroidal saponins in incurred rat
      plasma samples, after intragastric administration of the extract of Anemarrhena
      asphodeloides Bge. for a rat pharmacokinetic study. 

PMID- 25617742
TI  - The influence of handedness on hemispheric representation of tools: a survey.
AB  - An important debate exists in contemporary cognitive neuroscience about the
      innate or experience-dependent origin of the brain representation of conceptual
      categories. The 'domains of knowledge' hypothesis maintains that innate factors
      subsume the categorical organization at the brain level of animals, plant life
      and artefacts. On the other hand, the 'sensory-motor model of conceptual
      knowledge' and the embodied cognition theory attribute this categorical
      organization to experience-dependent factors. I tried to clarify this issue by
      surveying the influence that handedness could have on the lateralization of tools
      representation in the inferior fronto-parietal and posterior middle temporal
      cortices of the left hemisphere. The underlying assumption was that, if this
      lateralization results from innate mechanisms, then handedness should not
      influence this hemispheric asymmetry. If, on the other hand, this lateralization
      is due to the motor and somatosensory experiences made with the right dominant
      hand during the manipulation of tools and other artefacts, then this asymmetry
      should be inverted or strongly attenuated in left-handers. Results of the review
      strongly suggest that manual experience acquired during tool manipulation can
      influence the hemispheric representation of tools and other artefacts. They also
      suggest, however, that handedness-related embodiment is not fixed, but influenced
      by personal motor experiences (such as those made by left-handers who have been
      forced to use their right hand) and by social visual experiences (such as the
      fact that, living in a right-handed world, left-handers see more people in their
      environment who use the right rather than the left hand) during tool
      manipulation. 

PMID- 25617743
TI  - Characterization of the temporomandibular joint of the harbour porpoise (Phocoena
      phocoena) and Risso's dolphin (Grampus griseus).
AB  - OBJECTIVES: The temporomandibular joint (TMJ) in cetaceans is largely
      uncharacterized. This study aims to describe the macroscopic, microscopic,
      biochemical and biomechanical features of the TMJ of two species of the suborder
      Odontoceti: the harbour porpoise (Phocoena phocoena) and Risso's dolphin (Grampus
      griseus). Furthermore, we aim to elucidate the structure-function relationship of
      their TMJs and their possible role in echolocation. DESIGN: The TMJs from fresh
      cadaver heads of harbour porpoise (n=4) and Risso's dolphin (n=2) acquired from
      stranding were examined. Following macroscopical evaluation, the TMJs were
      investigated for their histological, mechanical and biochemical properties.
      RESULTS: The TMJs of the studied odontocetes were found to be fundamentally
      different from other mammals. Macroscopically, the TMJ lacks the typical joint
      cavity found in most mammals and is essentially a syndesmosis. Histological and
      microstructural analysis revealed that the TMJ discs were composed of haphazardly
      intersecting fibrous-connective tissue bundles separated by adipose tissue
      globules and various calibre blood vessels and nerve fibres. The collagen fibre
      composition was primarily collagen type I with lesser amounts of collagen type
      II. Sulphated glycosaminoglycan (sGAG) content was lower compared to other
      studied mammals. Finally, mechanical testing demonstrated the disc was stronger
      and stiffer in the dorsoventral direction than in the mediolateral direction.
      CONCLUSION: The spatial position of the TMJ, the absence of an articulating
      synovial joint, and the properties of the TMJ discs all reflect the unique
      suction-feeding mechanism adopted by the harbour porpoise and Risso's dolphin for
      underwater foraging. In addition, the presence of unique adipose globules, blood
      vessels and nerves throughout the discs may indicate a functional need beyond
      food apprehension. Instead, the disc may play a role in neurological sensory
      functions such as echolocation.

PMID- 25617744
TI  - A new role for wilms tumor protein 1: differential activities of + KTS and -KTS
      variants to regulate LHbeta transcription.
AB  - Luteinizing hormone (LH) is synthesized and secreted throughout the reproductive
      cycle from gonadotrope cells in the anterior pituitary, and is required for
      steroidogenesis and ovulation. LH contains an alpha-subunit common with FSH, and
      a unique LHbeta subunit that defines biological activity. Basal LHbeta
      transcription is low and stimulated by hypothalamic GnRH, which induces synthesis
      of early growth response protein-1 (Egr1), and stimulates binding of
      transcription factors Egr1 and steroidogenic factor-1 (SF1) on the promoter. WT1
      (Wilms tumor protein1) is a zinc finger transcription factor with an essential
      role in urogenital system development, and which regulates several reproductive
      genes via interactions with SF1 or binding to GC-rich elements such as Egr1
      binding sites. We investigated a potential role for WT1 in LHbeta transcription
      in clonal mouse gonadotrope LbetaT2 cells. WT1 was present in LbetaT2 and mouse
      pituitary cells, and protein bound to the endogenous LHbeta promoter.
      Interestingly, mRNAs for WT1(+KTS), which contains a three amino-acid insertion
      between the 3rd and 4th zinc fingers, and the WT1 (-KTS) variant were both
      expressed at significant levels. WT1 mRNAs and protein were decreased
      approximately 50% by GnRH treatment, under conditions where Egr1 mRNA and
      protein, and LHbeta transcription, were stimulated. Decreasing expression of mRNA
      for WT1 (-KTS) decreased stimulation of LHbeta and Egr1 by GnRH, whereas
      decreasing both WT1 (-KTS) and (+KTS) increased endogenous LHbeta transcription,
      and prevented LHbeta but not Egr1 stimulation by GnRH, suggesting differing
      biological activities for the WT1 isoforms. Overexpression of WT1 showed that
      WT1(-KTS) enhanced LHbeta promoter GnRH stimulation 2-to-3-fold and required the
      3'Egr1 site, but WT1(+KTS) repressed both basal and GnRH-stimulated LHbeta
      promoter activity by approximately 70%. Our data suggest that WT1 can modulate
      LHbeta transcription, with differential roles for the two WT1 variants; WT1 (
      KTS) enhances and WT1 (+KTS) suppresses transcription. 

PMID- 25617746
TI  - Anti-hyperuricemia effects of allopurinol are improved by Smilax riparia, a
      traditional Chinese herbal medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Smilax riparia are
      called "Niu-Wei-Cai" in traditional Chinese medicine (TCM). This botanical has
      been used in treating the symptoms of gout and other hyperuricemic-related
      conditions in TCM. Allopurinol is a commonly used medication to treat
      hyperuricemia and its complications. In this study, we evaluated whether Smilax
      riparia could enhance allopurinol's effects by decreasing the serum uric acid
      level in a hyperuricemic mouse model induced by potassium oxonate. MATERIALS AND
      METHODS: We examined the effects of allopurinol (5mg/kg) administration alone or
      in combination with Smilax riparia saponins (SRS, 500 mg/kg) on the serum uric
      acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a
      hyperuricemic mouse model. The effects of allopurinol alone or those of
      allopurinol plus SRS on the XOD activities were measured. Western blot analysis
      was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice. RESULTS:
      Compared with allopurinol alone, the combination of allopurinol and SRS
      significantly decreased the serum uric acid level and increased the urine uric
      acid level (both P<0.05), leading to the normalized serum and urine uric acid
      concentrations. Data on serum and urine creatinine and BUN supported these
      observations. The attenuation of hyperuricemia-induced renal dysfunction was
      linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the
      down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1.
      CONCLUSION: The anti-hyperuricemia effects of allopurinol are improved by Smilax
      riparia co-administration. The results were supported by the measurement of uric
      acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a
      potential value in clinical practice in the treatment of gout and other
      hyperuricemic conditions.

PMID- 25617745
TI  - A pathway-centric survey of somatic mutations in Chinese patients with colorectal
      carcinomas.
AB  - Previous genetic studies on colorectal carcinomas (CRC) have identified multiple
      somatic mutations in four candidate pathways (TGF-beta, Wnt, P53 and RTK-RAS
      pathways) on populations of European ancestry. However, it is under-studied
      whether other populations harbor different sets of hot-spot somatic mutations in
      these pathways and other oncogenes. In this study, to evaluate the mutational
      spectrum of novel somatic mutations, we assessed 41 pairs of tumor-stroma tissues
      from Chinese patients with CRC, including 29 colon carcinomas and 12 rectal
      carcinomas. We designed Illumina Custom Amplicon panel to target 43 genes,
      including genes in the four candidate pathways, as well as several known
      oncogenes for other cancers. Candidate mutations were validated by Sanger
      sequencing, and we further used SIFT and PolyPhen-2 to assess potentially
      functional mutations. We discovered 3 new somatic mutations in gene APC, TCF7L2,
      and PIK3CA that had never been reported in the COSMIC or NCI-60 databases.
      Additionally, we confirmed 6 known somatic mutations in gene SMAD4, APC, FBXW7,
      BRAF and PTEN in Chinese CRC patients. While most were previously reported in
      CRC, one mutation in PTEN was reported only in malignant endometrium cancer. Our
      study confirmed the existence of known somatic mutations in the four candidate
      pathways for CRC in Chinese patients. We also discovered a number of novel
      somatic mutations in these pathways, which may have implications for the
      pathogenesis of CRC. 

PMID- 25617747
TI  - Preventive treatment of calcium oxalate crystal deposition with immortal flowers.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A number of medicinal plants are used for their
      diuretic, urolithiatic and anti-inflammatory effects on urinary system problems
      in Turkey and the most common traditional remedy for kidney stones is the tea of
      immortal flowers. The aim of this study is to evaluate the preventive effect of
      infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG)
      and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney
      stones. MATERIALS AND METHOD: Sodium oxalate (Ox-70mg/kg intraperitoneally) was
      used to induce kidney stones on Wistar albino rats. At the same time, two
      different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and
      156mg/kg) were dissolved in the drinking water and administered to animals for 5
      days. Potassium citrate was used as positive control in the experiments. During
      the experiment, water intake, urine volume and body weights of the animals were
      recorded. At the end of the experiments, liver, kidney and body weights of the
      animals were determined; biochemical analysis were conducted on urine, blood and
      plasma samples. Histopathological changes in kidney tissues were examined and
      statistical analysis were evaluated. RESULTS: HS extract showed the highest
      preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a
      number of kidney stones were maximum in sodium oxalate group (stone formation
      score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels
      and increased citrate levels significantly. In addition, Helichrysum extracts
      regulated the negative changes in biochemical and hematological parameters
      occurred after Ox injection. CONCLUSIONS: We conclude that Helichrysum extracts
      could reduce the formation and growth of kidney stones in Ox-induced urolithiasis
      and can be beneficial for patients with recurrent stones. In addition, this is
      the first study on the preventive effect of immortal flowers.

PMID- 25617748
TI  - Ethnobotany of medicinal plants in the Thar Desert (Sindh) of Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of medicinal plants in health
      care practices among the rural communities provides the basis for natural drug
      discovery development. To the best of our knowledge, this is the first
      quantitative ethnobotanical investigation on the use of medicinal plants in the
      Thar Desert (Sindh) of Pakistan. METHODS: In total, 530 local informants and
      traditional healers were interviewed, using semistructured interviews. Various
      quantitative indices such as relative frequency of citation (RFC), use value
      (UV), informant consensus factor (ICF), fidelity level (FL), relative importance
      (RI), and the Jaccard Index (JI) were applied to the documented data. RESULTS:
      The traditional medical uses of 87 plant species belonging to 32 families were
      reported on. Amaranthaceae was the most-frequently cited (nine species), followed
      by Cucurbitaceae and Euphorbiaceae (six species each). The most dominant life
      form was herbs (73.56%). The most-used plant parts were leaves, with 65 reports
      (28.88%), followed by seeds (16%). The common mode of preparation reported was
      powder (25.75%), with 74% herbal medicines obtained from fresh plant materials.
      CONCLUSION: The ethnobotanical result documented in this study provides practical
      evidence about the use of medicinal plants among the inhabitants of the Thar
      Desert. Further, the findings revealed that the medicinal plants of the area are
      a major source of herbal drugs for primary health care used among the rural
      communities. This survey can be used as baseline information for further
      scientific investigation to develop new plant-based commercial drugs.

PMID- 25617749
TI  - Tradition of use on medicinal species in Valfurva (Sondrio, Italy).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the past Alpine populations were isolated from
      comforts of industrial and technological development present in large cities and,
      therefore, they were obliged to find in nature a source of sustenance and care.
      Traditional use of plant is a wealth of local knowledge that is likely to be
      lost. This work, carried out during 2012, aims to collect, analyze and process
      information on the species used for medicinal, veterinary, cosmetic, domestic,
      ritual and religious purposes by the inhabitants of Valfurva, in the Province of
      Sondrio (Italy). Furthermore it is a means for the preservation of local
      traditions regarding such uses and increases the ethnobotanical data from
      Northern Italy, till now poorly documented. METHODS: Our survey was conducted by
      semi-structered interviews. We interviewed 92 people, aged from 23 to 97 y.o.,
      born or resident in Valfurva. All information collected and concerning their use
      of plants, were analyzed using ethnobotanical indices such as Relative Frequency
      of Citation (RFC), Relative Importance (RI) and Factor Informant Consensus (FIC).
      RESULTS: Our study stated that people living in Valfurva use 126 species
      belonging to 48 families. Findings revealed that the most cited species is
      Achillea moschata Wulfen, with values of RFC and RI equal to 1.00 and 1.12
      respectively. Furthermore, 95 species were collected in the wild and 31 were
      cultivated. The most commonly used part plants were leaves, flowers, fruits,
      roots and complete aerial parts. The most frequent preparation methods were
      infusion, decoction and poultice. Among the recorded species, 91 of them are used
      for medicinal purposes, 72 for cooking, 19 for veterinary purposes, 10 for animal
      feed, 12 for cosmetic practices, 7 for religious or ritual purposes and 45 for
      domestic and various uses. The validity of the species use emerged in our survey
      is confirmed by scientific literature and research conducted on the same topics.
      CONCLUSIONS: This study increases ethnobotanical data coming from Italian Alps,
      whose regions have been so far hardly investigated. Our study confirms the
      interest in species already mentioned in previous surveys and placings. It also
      provides evidences which could be usefully exploited by new investigations aimed
      at knowing the active metabolites found responsible for plants use in traditional
      medicine.

PMID- 25617750
TI  - Determinants of anti-predator tactics in hatchling grass snakes (Natrix natrix).
AB  - Many organisms exhibit diverse anti-predator tactics, influenced by genetics and
      prior experience. In ectothermic taxa, offspring phenotypes are often sensitive
      to developmental temperatures. If the effectiveness of alternative anti-predator
      responses depends on thermally sensitive traits, then the temperatures
      experienced during embryonic life should also affect how offspring respond to an
      approaching predator. We incubated 16 clutches of Swedish grass snakes (Natrix
      natrix) at a range of developmental temperatures, and scored body size, colour
      pattern, locomotor performance and anti-predator responses of 213 hatchlings from
      those clutches. A hatchling snake's size and locomotor abilities were affected by
      its clutch of origin, its developmental temperature, and by an interaction
      between these two factors. Anti-predator tactics were strongly linked to
      locomotor ability, such that slower snakes tended to rely upon aggressive
      displays rather than flight. Incubation temperatures that generated slow (and
      thus aggressive) snakes also modified the colour of the snake's nuchal spot.
      Temperatures in the low to medium range generated mostly cream, white and orange
      spots, whereas medium to high temperatures generated more yellow spots.
      Incubation effects, and gene X environment interactions, thus may generate
      complex correlations between morphology, locomotor ability, and anti-predator
      tactics. 

PMID- 25617751
TI  - Liquid crystal-based glucose biosensor functionalized with mixed PAA and QP4VP
      brushes.
AB  - 4-Cyano-4'-pentylbiphenyl (5CB) in a transmission electron microscopy (TEM) grid
      was developed for glucose detection by coating with a monolayer of mixed polymer
      brushes using poly(acrylicacid-b-4-cynobiphenyl-4'-oxyundecylacrylate) (PAA-b
      LCP) and quaternized poly(4-vinylpyridine-b-4-cynobiphenyl-4'-oxyundecylacrylate)
      (QP4VP-b-LCP) (LCP stands for liquid crystal polymer) at the 5CB/aqueous
      interface. The resultant 5CB in TEM grid was functionalized with the PAA and
      QP4VP brushes, which were strongly anchored by the LCP block. The PAA brush
      rendered the 5CB/aqueous interface pH-responsive and the QP4VP brush immobilized
      glucose oxidase (GOx) through electrostatic interactions without the aid of
      coupling agents. The glucose was detected through a homeotropic-to-planar
      orientational transition of the 5CB observed through a polarized optical
      microscope (POM) under crossed polarizers. The optimum immobilization with a 0.78
      uM GOx solution on the dual-brush-coated TEM grid enabled glucose detection at
      concentrations higher than 0.5 mM with response times shorter than 180 s. This
      TEM grid glucose sensor provided a linear response of birefringence of the 5CB to
      glucose concentrations ranging from 0.5 to 11 mM with a Michaelis-Menten constant
      (Km) of 1.67 mM. This new and sensitive glucose biosensor has the advantages of
      low production cost, simple enzyme immobilization, high enzyme sensitivity and
      stability, and easy detection with POM, and may be useful for prescreening the
      glucose level in the human body.

PMID- 25617752
TI  - An amperometric nanobiosensor for the selective detection of K+-induced dopamine
      released from living cells.
AB  - A highly sensitive amperometric sensor has been studied for selective monitoring
      of K(+)-induced dopamine released from dopaminergic cells (PC12) which is based
      on an EDTA immobilized-poly(1,5-diaminonaphthalne) (poly-DAN) layer comprising
      graphene oxide (GO) and gold nanoparticles (GO/AuNPs). The integration of a
      negatively charged probe molecule on the poly-DAN/GO/AuNPs nanohybrid attained
      the signal enhancement to discriminate dopamine (DA) molecules from foreign
      species by catalytic effect and surface charge, and hydrogen bonding-based
      interactions with a probe molecule. The sensor performance and morphology were
      investigated using voltammetry, impedance spectrometry, SEM, and XPS.
      Experimental variables affecting the analytical performance of the sensor probe
      were optimized, and linear response was observed in the range of 10 nM-1 uM with
      a detection limit of 5.0 nM (+/-0.01) for DA. Then, the sensor was applied to
      monitor dopamine released from PC12 cells upon extracellular stimulation of K(+)
      ions. It was also confirmed that K(+)-induced dopamine release was inhibited by a
      calcium channel inhibitor (Nifidipine). The results demonstrated that the
      presented biosensor could be used as an excellent tool for monitoring the effect
      of exogenous agents on living cells and drug efficacy tests.

PMID- 25617753
TI  - Large-scale retrospective evaluation of regulated liquid chromatography-mass
      spectrometry bioanalysis projects using different total error approaches.
AB  - The current approach in regulated LC-MS bioanalysis, which evaluates the
      precision and trueness of an assay separately, has long been criticized for
      inadequate balancing of lab-customer risks. Accordingly, different total error
      approaches have been proposed. The aims of this research were to evaluate the
      aforementioned risks in reality and the difference among four common total error
      approaches (beta-expectation, beta-content, uncertainty, and risk profile)
      through retrospective analysis of regulated LC-MS projects. Twenty-eight projects
      (14 validations and 14 productions) were randomly selected from two GLP
      bioanalytical laboratories, which represent a wide variety of assays. The results
      show that the risk of accepting unacceptable batches did exist with the current
      approach (9% and 4% of the evaluated QC levels failed for validation and
      production, respectively). The fact that the risk was not wide-spread was only
      because the precision and bias of modern LC-MS assays are usually much better
      than the minimum regulatory requirements. Despite minor differences in magnitude,
      very similar accuracy profiles and/or conclusions were obtained from the four
      different total error approaches. High correlation was even observed in the width
      of bias intervals. For example, the mean width of SFSTP's beta-expectation is
      1.10-fold (CV=7.6%) of that of Saffaj-Ihssane's uncertainty approach, while the
      latter is 1.13-fold (CV=6.0%) of that of Hoffman-Kringle's beta-content approach.
      To conclude, the risk of accepting unacceptable batches was real with the current
      approach, suggesting that total error approaches should be used instead.
      Moreover, any of the four total error approaches may be used because of their
      overall similarity. Lastly, the difficulties/obstacles associated with the
      application of total error approaches in routine analysis and their desirable
      future improvements are discussed. 

PMID- 25617754
TI  - A study on the fundamental mechanism and the evolutionary driving forces behind
      aerobic fermentation in yeast.
AB  - Baker's yeast Saccharomyces cerevisiae rapidly converts sugars to ethanol and
      carbon dioxide at both anaerobic and aerobic conditions. The later phenomenon is
      called Crabtree effect and has been described in two forms, long-term and short
      term effect. We have previously studied under fully controlled aerobic conditions
      forty yeast species for their central carbon metabolism and the presence of long
      term Crabtree effect. We have also studied ten steady-state yeast cultures,
      pulsed them with glucose, and followed the central carbon metabolism and the
      appearance of ethanol at dynamic conditions. In this paper we analyzed those wet
      laboratory data to elucidate possible mechanisms that determine the fate of
      glucose in different yeast species that cover approximately 250 million years of
      evolutionary history. We determine overflow metabolism to be the fundamental
      mechanism behind both long- and short-term Crabtree effect, which originated
      approximately 125-150 million years ago in the Saccharomyces lineage. The
      "invention" of overflow metabolism was the first step in the evolution of aerobic
      fermentation in yeast. It provides a general strategy to increase energy
      production rates, which we show is positively correlated to growth. The
      "invention" of overflow has also simultaneously enabled rapid glucose consumption
      in yeast, which is a trait that could have been selected for, to "starve"
      competitors in nature. We also show that glucose repression of respiration is
      confined mainly among S. cerevisiae and closely related species that diverged
      after the whole genome duplication event, less than 100 million years ago. Thus,
      glucose repression of respiration was apparently "invented" as a second step to
      further increase overflow and ethanol production, to inhibit growth of other
      microbes. The driving force behind the initial evolutionary steps was most likely
      competition with other microbes to faster consume and convert sugar into biomass,
      in niches that were semi-anaerobic. 

PMID- 25617755
TI  - A truncated NLR protein, TIR-NBS2, is required for activated defense responses in
      the exo70B1 mutant.
AB  - During exocytosis, the evolutionarily conserved exocyst complex tethers Golgi
      derived vesicles to the target plasma membrane, a critical function for secretory
      pathways. Here we show that exo70B1 loss-of-function mutants express activated
      defense responses upon infection and express enhanced resistance to fungal,
      oomycete and bacterial pathogens. In a screen for mutants that suppress exo70B1
      resistance, we identified nine alleles of TIR-NBS2 (TN2), suggesting that loss-of
      function of EXO70B1 leads to activation of this nucleotide binding domain and
      leucine-rich repeat-containing (NLR)-like disease resistance protein. This NLR
      like protein is atypical because it lacks the LRR domain common in typical NLR
      receptors. In addition, we show that TN2 interacts with EXO70B1 in yeast and in
      planta. Our study thus provides a link between the exocyst complex and the
      function of a 'TIR-NBS only' immune receptor like protein. Our data are
      consistent with a speculative model wherein pathogen effectors could evolve to
      target EXO70B1 to manipulate plant secretion machinery. TN2 could monitor EXO70B1
      integrity as part of an immune receptor complex. 

PMID- 25617756
TI  - A novel phthalimide derivative, TC11, has preclinical effects on high-risk
      myeloma cells and osteoclasts.
AB  - Despite the recent advances in the treatment of multiple myeloma (MM), MM
      patients with high-risk cytogenetic changes such as t(4;14) translocation or
      deletion of chromosome 17 still have extremely poor prognoses. With the goal of
      helping these high-risk MM patients, we previously developed a novel phthalimide
      derivative, TC11. Here we report the further characterization of TC11 including
      anti-myeloma effects in vitro and in vivo, a pharmacokinetic study in mice, and
      anti-osteoclastogenic activity. Intraperitoneal injections of TC11 significantly
      delayed the growth of subcutaneous tumors in human myeloma-bearing SCID mice.
      Immunohistochemical analyses showed that TC11 induced apoptosis of MM cells in
      vivo. In the pharmacokinetic analyses, the Cmax was 2.1 MUM at 1 h after the
      injection of TC11, with 1.2 h as the half-life. TC11 significantly inhibited the
      differentiation and function of tartrate-resistant acid phosphatase (TRAP)
      positive multinucleated osteoclasts in mouse osteoclast cultures using M-CSF and
      RANKL. We also revealed that TC11 induced the apoptosis of myeloma cells
      accompanied by alpha-tubulin fragmentation. In addition, TC11 and lenalidomide,
      another phthalimide derivative, directly bound to nucleophosmin 1 (NPM1), whose
      role in MM is unknown. Thus, through multiple molecular interactions, TC11 is a
      potentially effective drug for high-risk MM patients with bone lesions. The
      present results suggest the possibility of the further development of novel
      thalidomide derivatives by drug designing. 

PMID- 25617757
TI  - Expression of digestive enzymes and nutrient transporters in Eimeria-challenged
      broilers.
AB  - Avian coccidiosis is a disease caused by the intestinal protozoa Eimeria. The
      site of invasion and lesions in the intestine is species-specific, for example E.
      acervulina affects the duodenum, E. maxima the jejunum, and E. tenella the ceca.
      Lesions in the intestinal mucosa cause reduced feed efficiency and body weight
      gain. The growth reduction may be due to changes in expression of digestive
      enzymes and nutrient transporters in the intestine. The objective of this study
      was to compare the expression of digestive enzymes, nutrient transporters and an
      antimicrobial peptide in broilers challenged with either E. acervulina, E. maxima
      or E. tenella. The genes examined included digestive enzymes (APN and SI),
      peptide and amino acid transporters (PepT1, ASCT1, b(0,+)AT/rBAT, B(0)AT, CAT1,
      CAT2, EAAT3, LAT1, y(+)LAT1 and y(+)LAT2), sugar transporters (GLUT1, GLUT2,
      GLUT5 and SGLT1), zinc transporter (ZnT1) and an antimicrobial peptide (LEAP2).
      Duodenum, jejunum, ileum and ceca were collected 7 days post challenge. E.
      acervulina challenge resulted in downregulation of various nutrient transporters
      or LEAP2 in the duodenum and ceca, but not the jejunum or ileum. E. maxima
      challenge produced both downregulation and upregulation of nutrient transporters
      and LEAP2 in all three segments of the small intestine and ceca. E. tenella
      challenge resulted in the downregulation and upregulation of nutrient
      transporters and LEAP2 in the jejunum, ileum and ceca, but not the duodenum. At
      the respective target tissue, E. acervulina, E. maxima and E. tenella infection
      caused common downregulation of APN, b(0,+)AT, rBAT, EAAT3, SI, GLUT2, GLUT5,
      ZnT1 and LEAP2. The downregulation of nutrient transporters would result in a
      decrease in the efficiency of protein and polysaccharide digestion and uptake,
      which may partially explain the weight loss. The downregulation of nutrient
      transporters may also be a cellular response to reduced expression of the host
      defense protein LEAP2, which would diminish intracellular pools of nutrients and
      inhibit pathogen replication. 

PMID- 25617758
TI  - Picornavirus IRES elements: RNA structure and host protein interactions.
AB  - Internal ribosome entry site (IRES) elements were discovered in picornaviruses.
      These elements are cis-acting RNA sequences that adopt diverse three-dimensional
      structures and recruit the translation machinery using a 5' end-independent
      mechanism assisted by a subset of translation initiation factors and various RNA
      binding proteins termed IRES transacting factors (ITAFs). Many of these factors
      suffer important modifications during infection including cleavage by
      picornavirus proteases, changes in the phosphorylation level and/or
      redistribution of the protein from the nuclear to the cytoplasm compartment.
      Picornavirus IRES are amongst the most potent elements described so far. However,
      given their large diversity and complexity, the mechanistic basis of its mode of
      action is not yet fully understood. This review is focused to describe recent
      advances on the studies of RNA structure and RNA-protein interactions modulating
      picornavirus IRES activity. 

PMID- 25617760
TI  - Normal table of embryonic development in the four-toed salamander, Hemidactylium
      scutatum.
AB  - We present a complete staging table of normal development for the lungless
      salamander, Hemidactylium scutatum (Caudata: Plethodontidae). Terrestrial egg
      clutches from naturally ovipositing females were collected and maintained at 15 
      degrees C in the laboratory. Observations, photographs, and time-lapse movies of
      embryos were taken throughout the 45-day embryonic period. The complete normal
      table of development for H. scutatum is divided into 28 stages and extends
      previous analyses of H. scutatum embryonic development (Bishop, 1920; Humphrey,
      1928). Early embryonic stage classifications through neurulation reflect criteria
      described for Xenopus laevis, Ambystoma maculatum and other salamanders. Later
      embryonic stage assignments are based on unique features of H. scutatum embryos.
      Additionally, we provide morphological analysis of gastrulation and neurulation,
      as well as details on external aspects of eye, gill, limb, pigmentation, and tail
      development to support future research related to phylogeny, comparative
      embryology, and molecular mechanisms of development. 

PMID- 25617759
TI  - New roles of glycosaminoglycans in alpha-synuclein aggregation in a cellular
      model of Parkinson disease.
AB  - The causes of Parkinson disease (PD) remain mysterious, although some evidence
      supports mitochondrial dysfunctions and alpha-synuclein accumulation in Lewy
      bodies as major events. The abnormal accumulation of alpha-synuclein has been
      associated with a deficiency in the ubiquitin-proteasome system and the autophagy
      lysosomal pathway. Cathepsin D (cathD), the major lysosomal protease responsible
      of alpha-synuclein degradation was described to be up-regulated in PD model. As
      glycosaminoglycans (GAGs) regulate cathD activity, and have been recently
      suggested to participate in PD physiopathology, we investigated their role in
      alpha-synuclein accumulation by their intracellular regulation of cathD activity.
      In a classical neuroblastoma cell model of PD induced by MPP+, the genetic
      expression of GAGs-biosynthetic enzymes was modified, leading to an increase of
      GAGs amounts whereas intracellular level of alpha-synuclein increased. The
      absence of sulfated GAGs increased intracellular cathD activity and limited alpha
      synuclein accumulation. GAGs effects on cathD further suggested that specific
      sequences or sulfation patterns could be responsible for this regulation. The
      present study identifies, for the first time, GAGs as new regulators of the
      lysosome degradation pathway, regulating cathD activity and affecting two main
      biological processes, alpha-synuclein aggregation and apoptosis. Finally, this
      opens new insights into intracellular GAGs functions and new fields of
      investigation for glycobiological approaches in PD and neurobiology. 

PMID- 25617761
TI  - Organic impurity profiling of 3,4-methylenedioxymethamphetamine (MDMA)
      synthesised from catechol.
AB  - This work examines the organic impurity profile of 3,4
      methylenedioxymethamphetamine (MDMA) that has been synthesised from catechol (1,2
      dihydroxybenzene), a common chemical reagent available in industrial quantities.
      The synthesis of MDMA from catechol proceeded via the common MDMA precursor
      safrole. Methylenation of catechol yielded 1,3-benzodioxole, which was brominated
      and then reacted with magnesium allyl bromide to form safrole. Eight organic
      impurities were identified in the synthetic safrole. Safrole was then converted
      to 3,4-methylenedioxyphenyl-2-propanone (MDP2P) using two synthetic methods:
      Wacker oxidation (Route 1) and an isomerisation/peracid oxidation/acid
      dehydration method (Route 2). MDMA was then synthesised by reductive amination of
      MDP2P. Thirteen organic impurities were identified in MDMA synthesised via Route
      1 and eleven organic impurities were identified in MDMA synthesised via Route 2.
      Overall, organic impurities in MDMA prepared from catechol indicated that
      synthetic safrole was used in the synthesis. The impurities also indicated which
      of the two synthetic routes was utilised. 

PMID- 25617762
TI  - Can a simple clinical test detect impairment of zopiclone and alcohol? - A
      randomized controlled trial.
AB  - PURPOSE: The risk of traffic accident involvement is increased among patients
      prescribed the z-hypnotic drug zopiclone. Clinical test observations able to
      indicate drug impairment are therefore essential. This study compared the
      findings of a simplified clinical test of impairment (SCTI) with those of a
      battery of computerized psychomotor tests of impairment (CPTI). METHODS: 16
      healthy young male volunteers attended a research unit on four different study
      days, receiving in randomized order either placebo, zopiclone 5mg, zopiclone
      10mg, or alcohol 50g. The SCTI was performed twice and the CPTI was performed
      three times on each study day, with blood samples being collected for drug
      analysis. RESULTS: The SCTI (and the CPTI) was able to demonstrate impairment at
      1.5h, but no major impairment was found at 7h with the SCTI, after intake of both
      zopiclone and ethanol. The CPTI detected a significantly higher proportion of
      impaired observations than the SCTI, both for zopiclone and for ethanol, at all
      concentration levels. The sensitivity of the clinical tests in detecting blood
      drug concentrations often associated with impairment, due to zopiclone (above
      23ng/ml) and alcohol (above 0.5g/l), was low, revealing 27 per cent and 18 per
      cent, respectively. The specificity, however, was higher, both for zopiclone (88
      per cent) and for alcohol (96 per cent). DISCUSSION: The SCTI may be a useful
      tool, especially during roadside investigation, when the police are in doubt as
      to whether the apprehended driver is impaired or not. A subject, who has consumed
      zopiclone or alcohol, tested with the SCTI, with one or more subtests diverging
      from a habitual result, is likely to have a blood zopiclone concentration above
      23ng/ml or a BAC above 0.5g/l. A negative result, however, is less helpful.

PMID- 25617764
TI  - Adhesion of several cell lines to Helicobacter pylori CagL is mediated by
      integrin alphaVbeta6 via an RGDLXXL motif.
AB  - The Helicobacter pylori type IV secretion system pilus protein CagL mediates
      interaction with host cells via its RGD motif. Here, we analyzed prerequisites
      for this interaction within CagL and on host cells. Various human cell lines were
      tested for adhesion to CagL. HT-29 and 23132/87 cells adhered to immobilized
      recombinant CagL in an RGD-dependent manner, while 293T (human embryonic kidney)
      and A549 cells did not. In a competitive ELISA, CagL competed with fibronectin
      for binding to the ectodomains of integrins alphaVbeta6 and alphaVbeta8 but not
      of alphaVbeta1, alphaVbeta3, alphaVbeta5 and alpha5beta1. Integrin alphaVbeta6
      acts as receptor for several viruses exposing an RGDLXXL motif. CagL also
      contains an RGDLXXL sequence. We individually mutated Leu79 and Leu82 of this
      motif to threonine, although both leucines are buried in the hydrophobic core.
      Surprisingly, the ability of CagL variants L79T and L82T to support adhesion was
      significantly reduced for 23132/87 cells and lost for MKN-45 and HT-29 cells. The
      role of integrin alphaVbeta6 in adhesion to CagL was investigated using SW480
      cells transfected with the integrin beta6 subunit (SW480beta6). These cells
      adhered to CagL in an RGD-dependent manner, while mock-transfected SW480 cells
      did not. The antibody 3G9 that blocks the function of integrin alphaVbeta6
      inhibited adhesion of SW480beta6, MKN-45, 23132/87 and HT-29 cells to CagL. In
      summary, CagL features an RGDLXXL motif facilitating adhesion of several human
      cell lines via integrin alphaVbeta6. The buried location of Leu79 and Leu82
      supports our previously published hypothesis that CagL partly unfolds upon
      integrin binding. 

PMID- 25617763
TI  - Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis
      are attenuated by neuroprotectin d1.
AB  - PURPOSE: Limbic epileptogenesis triggers molecular and cellular events that
      foster the establishment of aberrant neuronal networks that, in turn, contribute
      to temporal lobe epilepsy (TLE). Here we have examined hippocampal neuronal
      network activities in the pilocarpine post-status epilepticus model of limbic
      epileptogenesis and asked whether or not the docosahexaenoic acid (DHA)-derived
      lipid mediator, neuroprotectin D1 (NPD1), modulates epileptogenesis. METHODS:
      Status epilepticus (SE) was induced by intraperitoneal administration of
      pilocarpine in adult male C57BL/6 mice. To evaluate simultaneous hippocampal
      neuronal networks, local field potentials were recorded from multi-microelectrode
      arrays (silicon probe) chronically implanted in the dorsal hippocampus. NPD1 (570
      MUg/kg) or vehicle was administered intraperitoneally daily for five consecutive
      days 24 hours after termination of SE. Seizures and epileptiform activity were
      analyzed in freely-moving control and treated mice during epileptogenesis and
      epileptic periods. Then hippocampal dendritic spines were evaluated using Golgi
      staining. RESULTS: We found brief spontaneous microepileptiform activity with
      high amplitudes in the CA1 pyramidal and stratum radiatum in epileptogenesis.
      These aberrant activities were attenuated following systemic NPD1 administration,
      with concomitant hippocampal dendritic spine protection. Moreover, NPD1 treatment
      led to a reduction in spontaneous recurrent seizures. CONCLUSIONS: Our results
      indicate that NPD1 displays neuroprotective bioactivity on the hippocampal
      neuronal network ensemble that mediates aberrant circuit activity during
      epileptogenesis. Insight into the molecular signaling mediated by neuroprotective
      bioactivity of NPD1 on neuronal network dysfunction may contribute to the
      development of anti-epileptogenic therapeutic strategies.

PMID- 25617765
TI  - Functional analysis of duplicated Symbiosis Receptor Kinase (SymRK) genes during
      nodulation and mycorrhizal infection in soybean (Glycine max).
AB  - Association between legumes and rhizobia results in the formation of root
      nodules, where symbiotic nitrogen fixation occurs. The early stages of this
      association involve a complex of signalling events between the host and
      microsymbiont. Several genes dealing with early signal transduction have been
      cloned, and one of them encodes the leucine-rich repeat (LRR) receptor kinase
      (SymRK; also termed NORK). The Symbiosis Receptor Kinase gene is required by
      legumes to establish a root endosymbiosis with Rhizobium bacteria as well as
      mycorrhizal fungi. Using degenerate primer and BAC sequencing, we cloned
      duplicated SymRK homeologues in soybean called GmSymRKalpha and GmSymRKbeta.
      These duplicated genes have high similarity of nucleotide (96%) and amino acid
      sequence (95%). Sequence analysis predicted a malectin-like domain within the
      extracellular domain of both genes. Several putative cis-acting elements were
      found in promoter regions of GmSymRKalpha and GmSymRKbeta, suggesting a
      participation in lateral root development, cell division and peribacteroid
      membrane formation. The mutant of SymRK genes is not available in soybean;
      therefore, to know the functions of these genes, RNA interference (RNAi) of these
      duplicated genes was performed. For this purpose, RNAi construct of each gene was
      generated and introduced into the soybean genome by Agrobacterium rhizogenes
      mediated hairy root transformation. RNAi of GmSymRKbeta gene resulted in an
      increased reduction of nodulation and mycorrhizal infection than RNAi of
      GmSymRKalpha, suggesting it has the major activity of the duplicated gene pair.
      The results from the important crop legume soybean confirm the joint phenotypic
      action of GmSymRK genes in both mycorrhizal and rhizobial infection seen in model
      legumes. 

PMID- 25617766
TI  - Syndecan-3 and TFPI colocalize on the surface of endothelial-, smooth muscle-,
      and cancer cells.
AB  - BACKGROUND: Tissue factor (TF) pathway inhibitor (TFPI) exists in two isoforms;
      TFPIalpha and TFPIbeta. Both isoforms are cell surface attached mainly through
      glycosylphosphatidylinositol (GPI) anchors. TFPIalpha has also been proposed to
      bind other surface molecules, like glycosaminoglycans (GAGs). Cell surface
      TFPIbeta has been shown to exert higher anticoagulant activity than TFPIalpha,
      suggesting alternative functions for TFPIalpha. Further characterization and
      search for novel TFPI binding partners is crucial to completely understand the
      biological functions of cell associated TFPI. METHODS AND RESULTS: Potential
      association of TFPI to heparan sulphate (HS) proteoglycans in the syndecan family
      were evaluated by knock down studies and flow cytometry analysis. Cell surface
      colocalization was assessed by confocal microscopy, and native PAGE or
      immunoprecipitation followed by Western blotting was used to test for protein
      interaction. Heparanase was used to enzymatically degrade cell surface HS GAGs.
      Anticoagulant potential was evaluated using a factor Xa (FXa) activity assay.
      Knock down of syndecan-3 in endothelial,- smooth muscle- and breast cancer cells
      reduced the TFPI surface levels by 20-50%, and an association of TFPIalpha to
      syndecan-3 on the cell surface was demonstrated. Western blotting indicated that
      TFPIalpha was found in complex with syndecan-3. The TFPI bound to syndecan-3 did
      not inhibit the FXa generation. Removal of HS GAGs did not release TFPI antigen
      from the cells. CONCLUSIONS: We demonstrated an association between TFPIalpha and
      syndecan-3 in vascular cells and in cancer cells, which did not appear to depend
      on HS GAGs. No anticoagulant activity was detected for the TFPI associated with
      syndecan-3, which may indicate coagulation independent functions for this cell
      associated TFPI pool. This will, however, require further investigation.

PMID- 25617767
TI  - A nonlinear dynamics approach for incorporating wind-speed patterns into wind
      power project evaluation.
AB  - Wind-energy production may be expanded beyond regions with high-average wind
      speeds (such as the Midwest U.S.A.) to sites with lower-average speeds (such as
      the Southeast U.S.A.) by locating favorable regional matches between natural wind
      speed and energy-demand patterns. A critical component of wind-power evaluation
      is to incorporate wind-speed dynamics reflecting documented diurnal and seasonal
      behavioral patterns. Conventional probabilistic approaches remove patterns from
      wind-speed data. These patterns must be restored synthetically before they can be
      matched with energy-demand patterns. How to accurately restore wind-speed
      patterns is a vexing problem spurring an expanding line of papers. We propose a
      paradigm shift in wind power evaluation that employs signal-detection and
      nonlinear-dynamics techniques to empirically diagnose whether synthetic pattern
      restoration can be avoided altogether. If the complex behavior of observed wind
      speed records is due to nonlinear, low-dimensional, and deterministic system
      dynamics, then nonlinear dynamics techniques can reconstruct wind-speed dynamics
      from observed wind-speed data without recourse to conventional probabilistic
      approaches. In the first study of its kind, we test a nonlinear dynamics approach
      in an application to Sugarland Wind-the first utility-scale wind project proposed
      in Florida, USA. We find empirical evidence of a low-dimensional and nonlinear
      wind-speed attractor characterized by strong temporal patterns that match up well
      with regular daily and seasonal electricity demand patterns. 

PMID- 25617768
TI  - Implications of hybridization, NUMTs, and overlooked diversity for DNA Barcoding
      of Eurasian ground squirrels.
AB  - The utility of DNA Barcoding for species identification and discovery has
      catalyzed a concerted effort to build the global reference library; however, many
      animal groups of economical or conservational importance remain poorly
      represented. This study aims to contribute DNA barcode records for all ground
      squirrel species (Xerinae, Sciuridae, Rodentia) inhabiting Eurasia and to test
      efficiency of this approach for species discrimination. Cytochrome c oxidase
      subunit 1 (COI) gene sequences were obtained for 97 individuals representing 16
      ground squirrel species of which 12 were correctly identified. Taxonomic
      allocation of some specimens within four species was complicated by
      geographically restricted mtDNA introgression. Exclusion of individuals with
      introgressed mtDNA allowed reaching a 91.6% identification success rate.
      Significant COI divergence (3.5-4.4%) was observed within the most widespread
      ground squirrel species (Spermophilus erythrogenys, S. pygmaeus, S. suslicus,
      Urocitellus undulatus), suggesting the presence of cryptic species. A single
      putative NUMT (nuclear mitochondrial pseudogene) sequence was recovered during
      molecular analysis; mitochondrial COI from this sample was amplified following re
      extraction of DNA. Our data show high discrimination ability of 100 bp COI
      fragments for Eurasian ground squirrels (84.3%) with no incorrect assessments,
      underscoring the potential utility of the existing reference librariy for the
      development of diagnostic 'mini-barcodes'. 

PMID- 25617769
TI  - A novel tracking algorithm via feature points matching.
AB  - Visual target tracking is a primary task in many computer vision applications and
      has been widely studied in recent years. Among all the tracking methods, the mean
      shift algorithm has attracted extraordinary interest and been well developed in
      the past decade due to its excellent performance. However, it is still
      challenging for the color histogram based algorithms to deal with the complex
      target tracking. Therefore, the algorithms based on other distinguishing features
      are highly required. In this paper, we propose a novel target tracking algorithm
      based on mean shift theory, in which a new type of image feature is introduced
      and utilized to find the corresponding region between the neighbor frames. The
      target histogram is created by clustering the features obtained in the extraction
      strategy. Then, the mean shift process is adopted to calculate the target
      location iteratively. Experimental results demonstrate that the proposed
      algorithm can deal with the challenging tracking situations such as: partial
      occlusion, illumination change, scale variations, object rotation and complex
      background clutter. Meanwhile, it outperforms several state-of-the-art methods. 

PMID- 25617770
TI  - Cell cycle-independent phospho-regulation of Fkh2 during hyphal growth regulates
      Candida albicans pathogenesis.
AB  - The opportunistic human fungal pathogen, Candida albicans, undergoes
      morphological and transcriptional adaptation in the switch from commensalism to
      pathogenicity. Although previous gene-knockout studies have identified many
      factors involved in this transformation, it remains unclear how these factors are
      regulated to coordinate the switch. Investigating morphogenetic control by post
      translational phosphorylation has generated important regulatory insights into
      this process, especially focusing on coordinated control by the cyclin-dependent
      kinase Cdc28. Here we have identified the Fkh2 transcription factor as a
      regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a
      role distinct from its conserved function in cell cycle progression. In
      stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse
      pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before
      START in the cell cycle, the phosphorylation profile is transformed before
      reverting to the yeast profile. This transformation does not occur when
      stationary phase cells are reinoculated into fresh medium supporting yeast
      growth. Mass spectrometry and mutational analyses identified residues
      phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non
      phosphorylatable alanine altered the yeast phosphorylation profile and abrogated
      the characteristic transformation to the hyphal profile. Transcript profiling of
      the phosphorylation site mutant revealed that the hyphal phosphorylation profile
      is required for the expression of genes involved in pathogenesis, host
      interaction and biofilm formation. We confirmed that these changes in gene
      expression resulted in corresponding defects in pathogenic processes.
      Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3
      in a phosphorylation-dependent manner, thereby providing a possible mechanism by
      which the phosphorylation of Fkh2 regulates its specificity. Thus, we have
      discovered a novel cell cycle-independent phospho-regulatory event that subverts
      a key component of the cell cycle machinery to a role in the switch from
      commensalism to pathogenicity. 

PMID- 25617771
TI  - Impact of an immunohistochemistry-based universal screening protocol for Lynch
      syndrome in endometrial cancer on genetic counseling and testing.
AB  - OBJECTIVE: Evaluate effects of a Lynch syndrome universal screening protocol in
      newly diagnosed endometrial cancers on subsequent genetic counseling (GC) and
      germline testing (GT) referral and acceptance rates. METHODS: We performed a
      retrospective cohort study of women who underwent a hysterectomy for endometrial
      cancer at Barnes Jewish Hospital in St. Louis, MO between 1/1/2011 and 12/31/2013
      (n=637). An immunohistochemistry-based (IHC) universal screening protocol for
      Lynch syndrome was initiated on 12/17/2012. The cohorts consisted of women
      presenting prior to (Pre-Em-USP; n=395) and those presenting following (Em-USP;
      n=242) initiation of the universal screening protocol. GC and GT referrals were
      based on risk factors and/or IHC results. Comparisons were made using the
      Fisher's exact test and the Kruskal-Wallis test. RESULTS: A greater proportion of
      individuals in the Em-USP cohort underwent GT than in Pre-Em-USP (9.1% vs 4.8%,
      p<0.05). Of individuals with an IHC screening result suggestive of LS, those
      within the Em-USP cohort were significantly more likely to accept GC compared to
      those in the Pre-Em-USP cohort (95% vs 64%, p=0.02). Specifically within the Em
      USP cohort, patients referred to GC due to a concerning IHC screening result,
      versus those who were referred based on other risk factors, had a higher
      counseling acceptance rate (95% vs 61%, p=0.03) and underwent genetic testing
      more readily (76% vs 30%, p<0.001). CONCLUSIONS: Implementation of an IHC-based
      universal screening protocol for LS in endometrial cancer leads to higher
      acceptance of genetic counseling and higher rates of genetic testing compared to
      referral based on risk factors alone.

PMID- 25617772
TI  - Gynecologic Oncologist as surgical consultant: intraoperative consultations
      during general gynecologic surgery as an important focus of gynecologic oncology
      training.
AB  - OBJECTIVE: The aim of this study is to explore the previously unexamined role of
      the Gynecologic Oncologist as an intraoperative consultant during general
      gynecologic surgery. METHODS: Demographic and clinical data were collected on 98
      major gynecologic surgeries that included both a general Gynecologist and a
      Gynecologic Oncologist between October 2010 and August 2014. Data were analyzed
      using XLSTAT-Prov2014.2.02. RESULTS: Of 794 major gynecologic surgeries, 98
      (12.3%) cases that involved an intraoperative consultation were identified. There
      were 36 (37%) planned consults and 62 (63%) unplanned consults. Significantly
      more planned consults were during laparoscopy (100% v 58%; p<0.01) and
      significantly more unplanned consults were during laparotomy (42% v 0%; p<0.01).
      The majority of planned consults were for surgical training (86%) and the most
      common reasons for unplanned consults were adhesions (40%), bowel injury (19%),
      inability to identify ureter (19%), and cancer (11%). The most common
      interventions performed during unplanned consults were identification of anatomy
      (55%), lysis of adhesions (42%), and retroperitoneal dissection (27%). Average
      surgeon years in practice were significantly lower for unplanned consults (9 v
      15; p<0.01). A total of 25 major adverse events occurred in 15 cases with the
      majority occurring in cases with unplanned consults (23% v 3%; p<0.01). After
      controlling for laparotomy, unplanned consultation was not significantly
      associated with major events (OR=6.67, 95%CI 0.69-64.39; p=0.10). CONCLUSIONS:
      Gynecologic Oncologists play a pivotal role in the support of generalist
      colleagues during pelvic surgery. In this series, Gynecologic Oncologists were
      consulted frequently for complex major benign surgeries. It is important to
      incorporate the skills required of an intraoperative consultant into Gynecologic
      Oncology fellowship training.

PMID- 25617773
TI  - Aromatic catabolic pathway selection for optimal production of pyruvate and
      lactate from lignin.
AB  - Lignin represents an untapped feedstock for the production of fuels and
      chemicals, but its intrinsic heterogeneity makes lignin valorization a
      significant challenge. In nature, many aerobic organisms degrade lignin-derived
      aromatic molecules through conserved central intermediates including catechol and
      protocatechuate. Harnessing this microbial approach offers potential for lignin
      upgrading in modern biorefineries, but significant technical development is
      needed to achieve this end. Catechol and protocatechuate are subjected to
      aromatic ring cleavage by dioxygenase enzymes that, depending on the position,
      ortho or meta relative to adjacent hydroxyl groups, result in different products
      that are metabolized through parallel pathways for entry into the TCA cycle.
      These degradation pathways differ in the combination of succinate, acetyl-CoA,
      and pyruvate produced, the reducing equivalents regenerated, and the amount of
      carbon emitted as CO2-factors that will ultimately impact the yield of the
      targeted product. As shown here, the ring-cleavage pathways can be interchanged
      with one another, and such substitutions have a predictable and substantial
      impact on product yield. We demonstrate that replacement of the catechol ortho
      degradation pathway endogenous to Pseudomonas putida KT2440 with an exogenous
      meta-cleavage pathway from P. putida mt-2 increases yields of pyruvate produced
      from aromatic molecules in engineered strains. Even more dramatically, replacing
      the endogenous protocatechuate ortho pathway with a meta-cleavage pathway from
      Sphingobium sp. SYK-6 results in a nearly five-fold increase in pyruvate
      production. We further demonstrate the aerobic conversion of pyruvate to l
      lactate with a yield of 41.1 +/- 2.6% (wt/wt). Overall, this study illustrates
      how aromatic degradation pathways can be tuned to optimize the yield of a desired
      product in biological lignin upgrading.

PMID- 25617775
TI  - Virulence-associated gene pattern of porcine and human Yersinia enterocolitica
      biotype 4 isolates.
AB  - Yersinia enterocolitica 4/O:3 is the most important human pathogenic bioserotype
      in Europe and the predominant pathogenic bioserotype in slaughter pigs. Although
      many studies on the virulence of Y. enterocolitica strains have showed a broad
      spectrum of detectable factors in pigs and humans, an analysis based on a strict
      comparative approach and serving to verify the virulence capability of porcine Y.
      enterocolitica as a source for human yersiniosis is lacking. Therefore, in the
      present study, strains of biotype (BT) 4 isolated from Swiss slaughter pig
      tonsils and feces and isolates from human clinical cases were compared in terms
      of their spectrum of virulence-associated genes (yadA, virF, ail, inv, rovA,
      ymoA, ystA, ystB and myfA). An analysis of the associated antimicrobial
      susceptibility pattern completed the characterization. All analyzed BT 4 strains
      showed a nearly similar pattern, comprising the known fundamental virulence
      associated genes yadA, virF, ail, inv, rovA, ymoA, ystA and myfA. Only ystB was
      not detectable among all analyzed isolates. Importantly, neither the source of
      the isolates (porcine tonsils and feces, humans) nor the serotype (ST) had any
      influence on the gene pattern. From these findings, it can be concluded that the
      presence of the full complement of virulence genes necessary for human infection
      is common among porcine BT 4 strains. Swiss porcine BT 4 strains not only showed
      antimicrobial susceptibility to chloramphenicol, cefotaxime, ceftazidime,
      ciprofloxacin, colistin, florfenicol, gentamicin, kanamycin, nalidixic acid,
      sulfamethoxazole, streptomycin, tetracycline and trimethoprim but also showed
      100% antibiotic resistance to ampicillin. The human BT 4 strains revealed
      comparable results. However, in addition to 100% antibiotic resistance to
      ampicillin, 2 strains were resistant to chloramphenicol and nalidixic acid.
      Additionally, 1 of these strains was resistant to sulfamethoxazole. The results
      demonstrated that Y. enterocolitica BT 4 isolates from porcine tonsils, as well
      as from feces, show the same virulence-associated gene pattern and antibiotic
      resistance properties as human isolates from clinical cases, consistent with the
      etiological role of porcine BT 4 in human yersiniosis. Thus, cross-contamination
      of carcasses and organs at slaughter with porcine Y. enterocolitica BT 4 strains,
      either from tonsils or feces, must be prevented to reduce human yersiniosis. 

PMID- 25617774
TI  - Implementation and effectiveness of integrated trauma and addiction treatment for
      incarcerated men.
AB  - A controlled trial of Seeking Safety (SS) and Male-Trauma Recovery Empowerment
      Model (M-TREM) examined implementation and effectiveness of integrated group
      therapy for comorbid post-traumatic stress disorder (PTSD) and substance use
      disorder (SUD) on PTSD and mental health symptoms plus self-esteem and efficacy
      for incarcerated men. The study sample (n=230) was male inmates 18 years or older
      who were primarily non-white, high school graduates or equivalents, had childhood
      trauma histories, committed violent crimes, had serious mental illnesses, and
      resided in a maximum security prison. Incarcerated men, who screened positive for
      PTSD and SUD, were assigned randomly (n=142) or by preference (n=88) to receive
      SS or M-TREM, with a waitlist group of (n=93). Manualized interventions were
      group-administered for 14 weeks. Primary outcomes were PTSD and other mental
      health symptoms. Secondary outcomes were self-esteem, coping, and self-efficacy.
      SUD outcomes cannot be measured in a correctional setting. Implementation
      feasibility was exhibited by the ability to recruit, screen, assign, and retain
      participants. Effectiveness findings depended on sample, design, and method for
      analysis. Using a waitlist control group and no follow-up period, we found no
      aggregate effect of treatment on PTSD symptoms, although, when disaggregated, M
      TREM was found to improve PTSD severity and SS improved general mental health
      symptoms and psychological functioning. Using intent-to-treat and completer
      analyses, no significant differences were found in the relative performance
      between SS and M-TREM on primary or secondary outcomes. When longitudinal data
      were maximized and modeled in ways that reflect the hierarchical nature of the
      data, we found that SS and M-TREM performed better than no treatment on PTSD
      severity and secondary outcomes, and that treatment benefits endured. Findings
      cautiously support implementing either Seeking Safety or M-TREM to treat
      incarcerated men with co-morbid PTSD and addiction problems. 

PMID- 25617776
TI  - Investigation of shipping accident injury severity and mortality.
AB  - Shipping movements are operated in a complex and high-risk environment. Fatal
      shipping accidents are the nightmares of seafarers. With ten years' worldwide
      ship accident data, this study develops a binary logistic regression model and a
      zero-truncated binomial regression model to predict the probability of fatal
      shipping accidents and corresponding mortalities. The model results show that
      both the probability of fatal accidents and mortalities are greater for
      collision, fire/explosion, contact, grounding, sinking accidents occurred in
      adverse weather conditions and darkness conditions. Sinking has the largest
      effects on the increment of fatal accident probability and mortalities. The
      results also show that the bigger number of mortalities is associated with
      shipping accidents occurred far away from the coastal area/harbor/port. In
      addition, cruise ships are found to have more mortalities than non-cruise ships.
      The results of this study are beneficial for policy-makers in proposing efficient
      strategies to prevent fatal shipping accidents. 

PMID- 25617777
TI  - Development of a protocol to measure iron-55 in solid matrices in the
      environment.
AB  - The development of metrology of iron-55 in low-level radioactivity in
      environmental solid matrices was realised for conducting radioecological studies.
      A protocol was developed based on the adaptation of existing methods for the
      purification of iron-55 with selective chromatographic resin, which was then
      measured with liquid scintillation. The loss attached treatment chemical steps
      were quantified with elemental iron by Inductively Coupled Plasma Atomic Emission
      Spectrometry (ICP-AES). The tests were used to define the iron retention capacity
      of selective chromatographic resin, a key element in chemical treatment, and test
      sample size needed to reach the detection limit of 30 Bq kg(-1) dry. The solid
      samples were analysed with the developed protocol. The activities obtained from
      iron-55 were below the detection limit of 30 Bq kg(-1) dry.

PMID- 25617779
TI  - Documentation of time-scales for onset of natural attenuation in an aquifer
      treated by a crude-oil recovery system.
AB  - A pipeline transporting crude-oil broke in a nature reserve in 2009 and spilled
      5100 m(3) of oil that partly reached the aquifer and formed progressively a
      floating oil lens. Groundwater monitoring started immediately after the spill and
      crude-oil recovery by dual pump-and-skim technology was operated after oil lens
      formation. This study aimed at documenting the implementation of redox-specific
      natural attenuation processes in the saturated zone and at assessing whether
      dissolved compounds were degraded. Seven targeted water sampling campaigns were
      done during four years in addition to a routine monitoring of hydrocarbon
      concentrations. Liquid oil reached the aquifer within 2.5 months, and anaerobic
      processes, from denitrification to reduction of sulfate, were observable after 8
      months. Methanogenesis appeared on site after 28 months. Stable carbon isotope
      analyses after 16 months showed maximum shifts in delta(13)C of +4.9+/-0.220/00
      for toluene, +2.4+/-0.190/00 for benzene and +0.9+/-0.510/00 for ethylbenzene,
      suggesting anaerobic degradation of these compounds in the source zone.
      Estimations of fluxes of inorganic carbon produced by biodegradation revealed
      that, in average, 60% of inorganic carbon production was attributable to sulfate
      reduction. This percentage tended to decrease with time while the production of
      carbon attributable to methanogenesis was increasing. Within the investigation
      time frame, mass balance estimations showed that biodegradation is a more
      efficient process for control of dissolved concentrations compared to pumping and
      filtration on an activated charcoal filter.

PMID- 25617778
TI  - Deciphering the genetic programme triggering timely and spatially-regulated
      chitin deposition.
AB  - Organ and tissue formation requires a finely tuned temporal and spatial
      regulation of differentiation programmes. This is necessary to balance sufficient
      plasticity to undergo morphogenesis with the acquisition of the mature traits
      needed for physiological activity. Here we addressed this issue by analysing the
      deposition of the chitinous extracellular matrix of Drosophila, an essential
      element of the cuticle (skin) and respiratory system (tracheae) in this insect.
      Chitin deposition requires the activity of the chitin synthase Krotzkopf verkehrt
      (Kkv). Our data demonstrate that this process equally requires the activity of
      two other genes, namely expansion (exp) and rebuf (reb). We found that Exp and
      Reb have interchangeable functions, and in their absence no chitin is produced,
      in spite of the presence of Kkv. Conversely, when Kkv and Exp/Reb are co
      expressed in the ectoderm, they promote chitin deposition, even in tissues
      normally devoid of this polysaccharide. Therefore, our results indicate that both
      functions are not only required but also sufficient to trigger chitin
      accumulation. We show that this mechanism is highly regulated in time and space,
      ensuring chitin accumulation in the correct tissues and developmental stages.
      Accordingly, we observed that unregulated chitin deposition disturbs
      morphogenesis, thus highlighting the need for tight regulation of this process.
      In summary, here we identify the genetic programme that triggers the timely and
      spatially regulated deposition of chitin and thus provide new insights into the
      extracellular matrix maturation required for physiological activity. 

PMID- 25617780
TI  - Chemical speciation and source apportionment of fine particulate matter in
      Santiago, Chile, 2013.
AB  - Santiago is one of the largest cities in South America and has experienced high
      fine particulate matter (PM2.5) concentrations in fall and winter months for
      decades. To better understand the sources of fall and wintertime pollution in
      Santiago, PM2.5 samples were collected for 24 h every weekday from March to
      October 2013 for chemical analysis. Samples were analyzed for mass, elemental
      carbon (EC), organic carbon (OC), water soluble organic carbon (WSOC), water
      soluble nitrogen (WSTN), secondary inorganic ions, and particle-phase organic
      tracers for source apportionment. Selected samples were analyzed as monthly
      composites for organic tracers. PM2.5 concentrations were considerably higher in
      the coldest months (June-July), averaging (mean +/- standard deviation) 62+/-15
      MUg/m(3) in these two months. Average fine particle mass concentration during the
      study period was 40+/-20 MUg/m(3). Organic matter during the peak winter months
      was the major component of fine particles comprising around 70% of the particle
      mass. Source contributions to OC were calculated using organic molecular markers
      and a chemical mass balance (CMB) receptor model. The four combustion sources
      identified were wood smoke, diesel engine emission, gasoline vehicles, and
      natural gas. Wood smoke was the predominant source of OC, accounting for 58+/-42%
      of OC in fall and winter. Wood smoke and nitrate were the major contributors to
      PM2.5. In fall and winter, wood smoke accounted for 9.8+/-7.1 MUg/m(3) (21+/-15%)
      and nitrate accounted for 9.1+/-4.8 MUg/m(3) (20+/-10%) of fine PM. The sum of
      secondary inorganic ions (sulfate, nitrate, and ammonium) represented about 30%
      of PM2.5 mass. Secondary organic aerosols contributed only in warm months,
      accounting for about 30% of fine PM during this time.

PMID- 25617781
TI  - Estimating the contribution of photochemical particle formation to ultrafine
      particle number averages in an urban atmosphere.
AB  - Ultrafine particles (UFPs, diameter<100 nm) have gained major attention in the
      environmental health discussion due to a number of suspected health effects.
      Observations of UFPs in urban air reveal the presence of several, time-dependent
      particle sources. In order to attribute measured UFP number concentrations to
      different source type contributions, we analyzed observations collected at a
      triplet of observation sites (roadside, urban background, rural) in the city of
      Leipzig, Germany. Photochemical new particle formation (NPF) events can be the
      overwhelming source of UFP particles on particular days, and were identified on
      the basis of characteristic patterns in the particle number size distribution
      data. A subsequent segmentation of the diurnal cycles of UFP concentration
      yielded a quantitative contribution of NPF events to daily, monthly, and annual
      mean values. At roadside, we obtained source contributions to the annual mean UFP
      number concentration (diameter range 5-100 nm) for photochemical NPF events (7%),
      local traffic (52%), diffuse urban sources (20%), and regional background (21%).
      The relative contribution of NPF events rises when moving away from roadside to
      the urban background and rural sites (14 and 30%, respectively). Their
      contribution also increases when considering only fresh UFPs (5-20 nm) (21% at
      the urban background site), and conversely decreases when considering UFPs at
      bigger sizes (20-100 nm) (8%). A seasonal analysis showed that NPF events have
      their greatest importance on UFP number concentration in the months May-August,
      accounting for roughly half of the fresh UFPs (5-20 nm) at the urban background
      location. The simplistic source apportionment presented here might serve to
      better characterize exposure to ambient UFPs in future epidemiological studies.

PMID- 25617782
TI  - Variability in delta15N of intertidal brown algae along a salinity gradient:
      differential impact of nitrogen sources.
AB  - While it is generally agreed that delta(15)N of brown macroalgae can discriminate
      between anthropogenic and natural sources of nitrogen, this study provides new
      insights on net fractionation processes occurring in some of these species. The
      contribution of continental and marine sources of nitrogen to benthic macroalgae
      in the estuary-ria system of A Coruna (NW Spain) was investigated by analyzing
      the temporal (at a monthly and annual basis) and spatial (up to 10 km)
      variability of delta(15)N in the macroalgae Ascophyllum nodosum and three species
      of the genus Fucus (F. serratus, F. spiralis and F. vesiculosus). Total nitrate
      and ammonium concentrations and delta(15)N-DIN, along with salinity and
      temperature in seawater were also studied to address the sources of such
      variability. Macroalgal delta(15)N and nutrient concentrations decreased from
      estuarine to marine waters, suggesting larger dominance of anthropogenic nitrogen
      sources in the estuary. However, delta(15)N values of macroalgae were generally
      higher than those of ambient nitrogen at all temporal and spatial scales
      considered. This suggests that the isotopic composition of these macroalgae is
      strongly affected by fractionation during uptake, assimilation or release of
      nitrogen. The absence of correlation between macroalgal and water samples
      suggests that the delta(15)N of the species considered cannot be used for
      monitoring short-term changes. But their long lifespan and slow turnover rates
      make them suitable to determine the impact of the different nitrogen sources
      integrated over long-time periods.

PMID- 25617783
TI  - Characteristics of interventions targeting multiple lifestyle risk behaviours in
      adult populations: a systematic scoping review.
AB  - BACKGROUND: Modifiable lifestyle risk behaviours such as smoking, unhealthy diet,
      physical inactivity and alcohol misuse are the leading causes of major, non
      communicable diseases worldwide. It is increasingly being recognised that
      interventions which target more than one risk behaviour may be an effective and
      efficient way of improving people's lifestyles. To date, there has been no
      attempt to summarise the global evidence base for interventions targeting
      multiple risk behaviours. OBJECTIVE: To identify and map the characteristics of
      studies evaluating multiple risk behaviour change interventions targeted at adult
      populations in any country. METHODS: Seven bibliographic databases were searched
      between January, 1990, and January/ May, 2013. Authors of protocols, conference
      abstracts, and other relevant articles were contacted. Study characteristics were
      extracted and inputted into Eppi-Reviewer 4. RESULTS: In total, 220 studies were
      included in the scoping review. Most were randomised controlled trials (62%)
      conducted in the United States (49%), and targeted diet and physical activity
      (56%) in people from general populations (14%) or subgroups of general
      populations (45%). Very few studies had been conducted in the Middle East (2%),
      Africa (0.5%), or South America (0.5%). There was also a scarcity of studies
      conducted among young adults (1%), or racial and minority ethnic populations (4%)
      worldwide. CONCLUSIONS: Research is required to investigate the
      interrelationships of lifestyle risk behaviours in varying cultural contexts
      around the world. Cross-cultural development and evaluation of multiple risk
      behaviour change interventions is also needed, particularly in populations of
      young adults and racial and minority ethnic populations.

PMID- 25617784
TI  - Cytotoxic sesquiterpene lactone dimers isolated from Inula japonica.
AB  - Two new sesquiterpene lactone dimers, neojaponicone B (1) and inulanolide E (2)
      along with five known sesquiterpene lactone dimers (3-7, resp.) were isolated
      from the aerial parts of Inula japonica Thunb. The chemical structures of 1 and 2
      were elucidated by detailed spectroscopic analysis. The relative configuration of
      2 was confirmed by biomimetic transformation from the known sesquiterpene lactone
      dimer inulanolide A (3). The cytotoxicities of the isolated sesquiterpene lactone
      dimers were evaluated against 6T-CEM and Jurkat cell lines. All compounds showed
      potent cytotoxicities with IC50 value of 2.2-5.9MUm. 

PMID- 25617785
TI  - A fixed-bed column for phosphate removal from aqueous solutions using an andosol
      bagasse mixture.
AB  - It is difficult to eliminate phosphate from large volumes of water in batch mode
      using an adsorbent such as andosol. In a fixed-bed column, andosol has a very low
      permeability. In this study, andosol was mixed with bagasse to increase
      permeability. The mixture was then applied for the adsorption of phosphate in a
      fixed-bed column. Optimum and stable permeability was obtained with a 50/50
      mixture of andosol and bagasse. The maximum adsorption capacity obtained was 4.18
      mg/g for a column with a bed depth of 1.8 cm and a flow rate of 4 mL/min. The
      experimental data fit best to Thomas and Adam-Bohart models. These experimental
      results were applied in the treatment of natural phosphate-containing water from
      Yaounde Municipal Lake in Cameroon. Column performance increased by 60% due to
      the presence of Ca(2+) and Mg(2+) in the natural water. These cations form
      complexes with phosphate at the andosol surface. The standard enthalpy 15.964
      kj/mol indicated that phosphate adsorption on andosol-bagasse mixture was an
      endothermic process. Kinetic experiments demonstrated that phosphate adsorption
      fitted better with a pseudo-second-order model.

PMID- 25617786
TI  - Impact of water management practice scenarios on wastewater flow and contaminant
      concentration.
AB  - Due to frequent droughts and rapid population growth in urban areas, the adoption
      of practices to reduce the usage of fresh water is on the rise. Reduction in
      usage of fresh water can be achieved through various local water management
      practices (WMP) such as Water Demand Management (WDM) and use of alternative
      water sources such as Greywater Recycling (GR) and Rainwater Harvesting (RH).
      While the positive effects of WMPs have been widely acknowledged, the
      implementation of WMPs is also likely to lower the wastewater flow and increase
      the concentration of contaminants in sewage. These in turn can lead to increases
      in sewer problems such as odour and corrosion. This paper analyses impacts of
      various WMP scenarios on wastewater flow and contaminant load. The Urban Volume
      and Quality (UVQ) model was used to simulate wastewater flow and the associated
      wastewater contaminants from different WMP scenarios. The wastewater parameters
      investigated were those which influence odour and corrosion problems in sewerage
      networks due to the formation of hydrogen sulphide. These parameters are:
      chemical oxygen demand (COD), nitrate (NO3(-)), sulphate (SO4(2-)), sulphide (S(2
      )) and iron (Fe) that were contributed by the households (not including the
      biochemical process in sewer pipe). The results will help to quantify the impact
      of WMP scenarios on odour and corrosion in sewerage pipe networks. Results show
      that the implementation of a combination of WDM and GR had highly increased the
      concentration of all selected contaminant that triggered the formation of
      hydrogen sulphide, namely COD, sulphate and sulphide. On the other hand, the RH
      scenario had the least increase in the concentration of the contaminants, except
      iron concentrations. The increase in iron concentrations is actually beneficial
      because it inhibits the formation of hydrogen sulphide. 

PMID- 25617787
TI  - Reorienting land degradation towards sustainable land management: linking
      sustainable livelihoods with ecosystem services in rangeland systems.
AB  - This paper identifies new ways of moving from land degradation towards
      sustainable land management through the development of economic mechanisms. It
      identifies new mechanisms to tackle land degradation based on retaining critical
      levels of natural capital whilst basing livelihoods on a wider range of ecosystem
      services. This is achieved through a case study analysis of the Kalahari
      rangelands in southwest Botswana. The paper first describes the socio-economic
      and ecological characteristics of the Kalahari rangelands and the types of land
      degradation taking place. It then focuses on bush encroachment as a way of
      exploring new economic instruments (e.g. Payments for Ecosystem Services)
      designed to enhance the flow of ecosystem services that support livelihoods in
      rangeland systems. It does this by evaluating the likely impacts of bush
      encroachment, one of the key forms of rangeland degradation, on a range of
      ecosystem services in three land tenure types (private fenced ranches, communal
      grazing areas and Wildlife Management Areas), before considering options for more
      sustainable land management in these systems. We argue that with adequate policy
      support, economic mechanisms could help reorient degraded rangelands towards more
      sustainable land management. 

PMID- 25617788
TI  - Bioassessment of trace element contamination of Mediterranean coastal waters
      using the seagrass Posidonia oceanica.
AB  - A large scale survey of the trace element (TE) contamination of Mediterranean
      coastal waters was performed from the analysis of Ag, As, Cd, Cu, Hg, Ni and Pb
      in the bioindicator Posidonia oceanica, sampled at 110 sites differing by their
      levels of exposure to contaminants. The holistic approach developed in this
      study, based on the combined utilization of several complementary monitoring
      tools, i.e. water quality scale, pollution index and spatial analysis, accurately
      assessed the TE contamination rate of Mediterranean coastal waters. In
      particular, the mapping of the TE contamination according to a new proposed 5
      level water quality scale precisely outlined the contamination severity along
      Mediterranean coasts and facilitated interregional comparisons. Finally, the
      reliability of the use of P. oceanica as bioindicator species was again
      demonstrated through several global, regional and local detailed case studies.
      NB: The designations employed and the presentation of the information in this
      document do not imply the expression of any opinion whatsoever on the part of the
      authors concerning the legal status of any country, territory, city or area or of
      its authorities, or concerning the delimitation of its frontiers or boundaries. 

PMID- 25617789
TI  - Composite scaffolds for controlled drug release: role of the polyurethane
      nanoparticles on the physical properties and cell behaviour.
AB  - Localised delivery of appropriate biomolecule/drug(s) can be suitable to prevent
      postoperative infections and inflammation after scaffold implantation in vivo. In
      this study composite shell scaffolds, based on an internally produced bioactive
      glass and a commercial hydroxyapatite, were surface coated with a uniform
      polymeric layer, embedded with thermo-stable polyesterurethane (PU)-based
      nanoparticles (NPs), containing an anti-inflammatory drug (indomethacin; IDCM).
      The obtained functionalised scaffolds were subjected to physico-mechanical and
      biological characterisations. The results indicated that NPs incorporation into
      the gelatin coating of the composite scaffolds: 1) not changed significantly the
      micro-architecture of the scaffolds in terms of mean pore diameter and pore size
      distribution; 2) increased the compressive modulus; and 3) allowed to a sustained
      IDMC release (65-70% of the loaded-drug) within the first week of incubation in
      physiological solution. On the other hand, the NPs incorporation did not affect
      the biocompatibility of composite scaffolds, as evidenced by viability and
      alkaline phosphatase (ALP) activity of MG63 human osteoblast-like cells. 

PMID- 25617790
TI  - Strengthening of causality assessment of adverse events following immunization in
      the WHO South East Asia and Western Pacific regions: Lessons from the 2014 SEAR
      inter-country workshop.
AB  - BACKGROUND: Poorly managed AEFI undermine immunization programs. Improved
      surveillance in SEAR countries means more AEFIs but management varies. SEAR
      brought countries together to share AEFI experiences, and learn more about
      causality assessment. METHODS: Three day 10 country workshop (9 SEAR; 1 WPR).
      Participants outlined county AEFI experiences, undertook causality assessment for
      8 AEFIs using WHO methodology, critiqued the process by questionnaire and had a
      discussion. RESULTS: All 10 valued AEFI monitoring and causality assessment, and
      praised the opportunity to share experiences. Participants determined a range of
      AEFI and causality assessment needs in SEAR such as adapting WHO Algorithm,
      CIOMS/Brighton definitions, WHO verbal autopsy to fit context, requesting a
      practical guide--AEFI definition, time interval, rates of AEFI for different
      vaccines and evidence for vaccine related causes of death under 24h. CONCLUSIONS:
      LMIC need WHO AEFI tools adapted to better fit LMIC. Learning from each other
      builds capacity. Sharing AEFI experiences, case reviews help LMIC improve
      practices.

PMID- 25617791
TI  - Inference of other's internal neural models from active observation.
AB  - Recently, there have been several attempts to replicate theory of mind, which
      explains how humans infer the mental states of other people using multiple
      sensory input, with artificial systems. One example of this is a robot that
      observes the behavior of other artificial systems and infers their internal
      models, mapping sensory inputs to the actuator's control signals. In this paper,
      we present the internal model as an artificial neural network, similar to
      biological systems. During inference, an observer can use an active incremental
      learning algorithm to guess an actor's internal neural model. This could
      significantly reduce the effort needed to guess other people's internal models.
      We apply an algorithm to the actor-observer robot scenarios with/without prior
      knowledge of the internal models. To validate our approach, we use a physics
      based simulator with virtual robots. A series of experiments reveal that the
      observer robot can construct an "other's self-model", validating the possibility
      that a neural-based approach can be used as a platform for learning cognitive
      functions. 

PMID- 25617792
TI  - Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and
      phenyzoline in rats.
AB  - Although imidazoline I2 receptor ligands have been used as discriminative
      stimuli, the role of efficacy of I2 receptor ligands as a critical determinant in
      drug discrimination has not been explored. This study characterized the
      discriminative stimulus effects of selective imidazoline I2 receptor ligands
      BU224 (a low-efficacy I2 receptor ligand) and phenyzoline (a higher efficacy I2
      receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to
      discriminate 5.6mg/kg BU224 or 32mg/kg phenyzoline (i.p.) from their vehicle in a
      two-lever food-reinforced drug discrimination procedure, respectively. All rats
      acquired the discriminations after an average of 18 (BU224) and 56 (phenyzoline)
      training sessions, respectively. BU224 and phenyzoline completely substituted for
      one another symmetrically. Several I2 receptor ligands (tracizoline, CR4056,
      RS45041, and idazoxan) all occasioned>80% drug-associated lever responding in
      both discriminations. The I2 receptor ligand 2-BFI and a monoamine oxidase
      inhibitor harmane occasioned>80% drug-associated lever responding in rats
      discriminating BU224. Other drugs that occasioned partial or less substitution to
      BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and
      agmatine. Clonidine, methamphetamine and morphine also only produced partial
      substitution to phenyzoline cue. Naltrexone, dopamine D2 receptor antagonist
      haloperidol and serotonin (5-HT)2A receptor antagonist MDL100907 failed to alter
      the discriminative stimulus effects of BU224 or phenyzoline. Combined, these
      results are the first to demonstrate that BU224 and phenyzoline can serve as
      discriminative stimuli and that the low-efficacy I2 receptor ligand BU224 shares
      similar discriminative stimulus effects with higher-efficacy I2 receptor ligands
      such as phenyzoline and 2-BFI. 

PMID- 25617793
TI  - The synergistic antitumor effects of all-trans retinoic acid and C-phycocyanin on
      the lung cancer A549 cells in vitro and in vivo.
AB  - The anticancer effects and mechanism of all-trans retinoic acid (ATRA), C
      phycocyanin (C-PC) or ATRA+C-PC on the growth of A549 cells were studied in in
      vitro and in vivo experiments. The effects of C-PC and ATRA on the growth of A549
      cells were determined. The expression of CDK-4 and caspase-3, and the cellular
      apoptosis levels were detected. The tumor model was established by subcutaneous
      injection of A549 cells to the left axilla of the NU/NU mice. The weights of
      tumor and the spleen were tested. The viabilities of T-cells and spleen cells,
      TNF levels, the expression of Bcl-2 protein and Cyclin D1 gene were examined.
      Results showed both C-PC and ATRA could inhibit the growth of tumor cells in vivo
      and in vitro. ATRA+C-PC cooperatively showed a higher antitumor activity. The
      dosage of ATRA was reduced when it was administered with C-PC together, and the
      toxicity was reduced as well. ATRA+C-PC could decrease CDK-4 but increase caspase
      3 protein expression level and induce cell apoptosis. ATRA alone could lower the
      activities of T lymphocytes and spleen weights, but the combination with C-PC
      could effectively promote viability of T cells and spleen. C-PC+ATRA could up
      regulate TNF, and down-regulate Bcl-2 and Cyclin D1 gene. The combination might
      inhibit tumor growth by inhibiting the progress of cell cycle, inducing cell
      apoptosis and enhancing the body immunity. 

PMID- 25617794
TI  - Protective effects of friedelin isolated from Azima tetracantha Lam. against
      ethanol-induced gastric ulcer in rats and possible underlying mechanisms.
AB  - The current study was aimed to investigate the gastroprotective effects of
      friedelin isolated from the hexane extract of leaves of Azima tetracantha.
      Ethanol-induced gastric ulcer model was used to investigate the gastroprotective
      effects of friedelin. Antioxidant enzymes, lipid peroxidation, nitric oxide,
      gastric vascular permeability, pro and anti-inflammatory cytokines and apoptosis
      level have been investigated. Ethanol caused severe gastric damage and friedelin
      pretreatment protected against its deleterious role. Antioxidant enzyme
      activities, anti-inflammatory cytokines, prostaglandin E2 (PGE2), constitutive
      nitric oxide synthase (cNOS) and mucus weight have been increased significantly.
      However, the vascular permeability, pro-inflammatory cytokines, inducible nitric
      oxide synthase (iNOS), caspase-3 and apoptosis level have significantly been
      decreased after friedelin ingestion. The present study has clearly demonstrated
      the anti-ulcer potential of friedelin, these findings suggested that friedelin
      could be a new useful natural gastroprotective tool against gastric ulcer. 

PMID- 25617795
TI  - Involvement of alpha1B-adrenoceptors in the anti-immobility effect of imipramine
      in the tail suspension test.
AB  - Imipramine is a tricyclic antidepressant inhibitor of norepinephrine and
      serotonin neuronal reuptake. The roles of specific alpha1-adrenoceptor subtypes
      that might be targeted by the increased synaptic levels of noradrenaline induced
      by imipramine are not well understood. This study investigates the alpha1
      adrenoceptor subtypes involved in the anti-immobility effect of imipramine in the
      mouse tail suspension test. The anti-immobility effect of imipramine (32mg/kg,
      i.p.) was significantly antagonised by the non-subtype-selective alpha1
      adrenoceptor antagonist prazosin (0.5 and 1.0mg/kg, i.p.). Neither the selective
      alpha1A-adrenoceptor antagonist 5-methyl-3-[3-[3-[4-[2-(2,2,2,
      trifluroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H,3H)-pyrimidinedione (RS
      100329, 0.5 and 1.0mg/kg) nor the selective alpha1D-adrenoceptor antagonist 8-[2
      [4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione
      dihydrochloride, (BMY-7378, up to 1.0mg/kg, i.p.) affected the anti-immobility
      effect of imipramine. However, the anti-immobility effect of imipramine was
      significantly antagonised by the selective alpha1B-adrenoceptor antagonist (2S)-4
      (4-amino-6,7-dimethoxy-2-quinazolinyl)-2-[[(1,1-dimethylethyl)amino]carbonyl]-1
      piperazinecarboxylate (L-765,314). In addition, mice treated only with RS-100329
      or BMY-7378, but not with L-765,314, showed reduced immobility times in
      comparison to mice treated with vehicle. These results indicate that the
      selective antagonism of alpha1A- and alpha1D-adrenoceptors results in
      antidepressant-like effects and that the alpha1B-subtype is the main target for
      the increased levels of noradrenaline caused by imipramine. 

PMID- 25617796
TI  - W-7 inhibits voltage-dependent K(+) channels independent of calmodulin activity
      in rabbit coronary arterial smooth muscle cells.
AB  - We investigated the effect of W-7, a calmodulin inhibitor, on voltage-dependent
      K(+) (Kv) channels in freshly isolated coronary arterial smooth muscle cells
      using the whole-cell patch clamp technique. The amplitude of Kv currents was
      inhibited by W-7 in a concentration-dependent manner, with an IC50 value of
      3.38+/-0.47MUM and a Hill coefficient of 0.84+/-0.10. W-7 shifted the activation
      curve to a more positive potential but had no significant effect on the
      inactivation curve, which indicated that W-7 inhibited the Kv current in a closed
      state of the Kv channel. Another calmodulin inhibitor, W-13, had no significant
      effect on Kv currents and did not change the inhibitory effect of W-7 on Kv
      channels. From these results, we conclude that W-7 inhibited the Kv current in a
      dose-dependent manner, but this inhibition occurred independent of calmodulin
      activity and in a closed (inactivated) state of the Kv channels. 

PMID- 25617797
TI  - Thiazole derivatives as inhibitors of cyclooxygenases in vitro and in vivo.
AB  - Cyclooxygenases (COXs) are important membrane-bound heme containing enzymes
      important in platelet activation and inflammation. COX-1 is constitutively
      expressed in most cells whereas COX-2 is an inducible isoform highly expressed in
      inflammatory conditions. Studies have been carried out to evaluate thiazole
      derivatives as anti-inflammatory molecules. In this study, we investigated the in
      vitro and in vivo effects of two novel thiazole derivatives compound 1 (N-[4-(4
      hydroxy-3-methoxyphenyl)-1,3-thiazol-2-yl] acetamide) and compound 2 (4-(2-amino
      1,3-thiazol-4-yl)-2-methoxyphenol) on prostaglandin E2 (PGE2) production and COX
      activity in inflammatory settings. Our results reveal a potent inhibition of both
      compound 1 (IC50 9.01+/-0.01uM) and 2 (IC50 11.65+/-6.20uM) (Mean+/-S.E.M.) on
      COX-2-dependent PGE2 production. We also determined whether COX-1 activity was
      inhibited. Using cells stably over-expressing COX-1 and human blood platelets, we
      showed that compound 1 is a specific inhibitor of COX-1 with IC50 (5.56*10(-8)+/
      2.26*10(-8)uM), whereas compound 2 did not affect COX-1. Both compounds exhibit
      anti-inflammatory effect in the dorsal air pouch model of inflammation as shows
      by inhibition of PGE2 secretion. Modeling analysis of docking in the catalytic
      site of COX-1 or COX-2 further confirmed the difference in the effect of these
      two compounds. In conclusion, this study contributes to the design of new anti
      inflammatory agents and to the understanding of cyclooxygenase inhibition by
      thiazole. 

PMID- 25617798
TI  - Acute cytotoxicity of MIRA-1/NSC19630, a mutant p53-reactivating small molecule,
      against human normal and cancer cells via a caspase-9-dependent apoptosis.
AB  - Although numerous studies have focused on the mechanisms of action of the
      candidate chemotherapeutic drug MIRA-1/NSC19630, initially described as a mutant
      p53-reactivating small molecule, the issue of its toxicological evaluation
      remains open. Here, we devised a strategy to examine the effects of MIRA-1 on a
      variety of human normal cells and cancer cell lines. First, we demonstrated a
      massive and rapid (within 2 hours) MIRA-1 apoptotic effect on human normal
      primary epithelial cells as shown using an intestinal mucosa explant assay. MIRA
      1 was also cytotoxic to primary and subcultured human mesenchymal cells.
      Interestingly these effects were restricted to actively proliferating cells.
      Second, MIRA-1 acute toxicity was independent of p53, since it occurred in human
      normal cells with increased or silenced p53 expression level, in cancer cells
      derived from solid or liquid tumors, with either mutated or wt TP53, and in
      cancer cells devoid of p53. Third, combined pharmacological and genetic
      approaches showed that MIRA-1 acute cytotoxicity was mediated by a caspase-9
      dependent apoptosis. In conclusion, our strategy unveils the limitations of the
      targeted action of a small molecule designed to reactivate mutant p53. 

PMID- 25617799
TI  - PTP1B promotes cell proliferation and metastasis through activating src and
      ERK1/2 in non-small cell lung cancer.
AB  - Previous studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B)
      can promote tumor progression in breast cancer, colon cancer and prostate cancer.
      Additionally, PTP1B acts as a tumor suppressor in other cancers, such as
      esophageal cancer and lymphoma. These findings suggest that PTP1B functions as a
      double-facet molecule in tumors, and the role of PTP1B in non-small cell lung
      cancer (NSCLC) is unknown. The present study demonstrates that the expression of
      PTP1B in NSCLC tissue is significantly higher than its expression in benign lung
      disease and is associated with the stage and overall survival (OS) of NSCLC
      patients. In vitro studies have demonstrated that PTP1B promotes the
      proliferation and metastasis of NSCLC cells by reducing the expression of p-src
      (Tyr527), which activates src and ERK1/2. This study provides the first
      exploration of the role of PTP1B in the proliferation and metastasis of NSCLC and
      subsequently elucidates the role of PTP1B in cancer. Our study uncovered that
      PTP1B can promote NSCLC proliferation and metastasis by activating src and
      subsequently ERK1/2 and provides a theoretical basis for future applications of
      PTP1B inhibitors in the treatment of NSCLC. 

PMID- 25617800
TI  - Metabolic tumor burden: a new promising way to reach precise personalized therapy
      in PDAC.
AB  - Pancreatic cancer is currently one of the deadliest solid malignancies and
      pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic
      cancer. In the past decade, diagnostics and surgical techniques for PDAC have
      been evolving steadily; however, clinical outcomes of patients with PDAC have
      shown little, if any, improvement. Subgroup classification based on accurate
      prediction of prognosis in patients with pancreatic cancer is important for
      treatment selection and clinical decision-making. The traditional method to
      evaluate prognosis relies on the TNM staging system, but it may not reflect the
      true status of every patient due to individual biological differences.
      Metabolomics is a field of study that involves the identification and
      quantification of metabolites present in a biological system. Analysis of
      metabolic differences between cancerous and noncancerous tissues can provide
      novel insights into tumor biology that are closely associated with disease
      prognosis and diagnosis. Therefore, evaluation of metabolic tumor burden may
      improve the accuracy of the clinical decision-making process, thereby
      facilitating optimization of the treatment strategies for pancreatic cancer. 

PMID- 25617801
TI  - The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in
      serous ovarian cancer metastasis.
AB  - Complete resection is pivotal to improve survival to epithelial ovarian cancer
      (EOC). Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) is
      involved in multiple signaling pathways and it has opposite roles in different
      cancers. The present study aimed to identify C3G expression in ovarian tissue
      samples from patients with EOC and to explore its association with tumor grade.
      Eighty-seven archival paraffin-embedded, formalin-fixed, ovarian cancer tissues
      with serous histology were stained for C3G by immunohistochemistry. To evaluate
      the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer
      (SOC) were investigated. Additionally, C3G was knocked down in SKOV3 and HEY
      cells. C3G regulated Rap1 activity and high Rap1 activity was correlated with
      poor differentiation, advanced FIGO stage, and unsuccessful cytoreductive surgery
      of SOC. Knockdown of C3G suppressed cell invasion, intravasation and
      extravasation, and reduced Rap1 activity and secretion of matrix
      metalloproteinase (MMP)-2 and MMP-9. C3G-mediated activation of Rap1 could direct
      the tumor pattern of human SOC by promoting the secretion of MMP-2 and MMP-9.
      These results suggest that C3G is involved in the metastatic spread of EOC. 

PMID- 25617803
TI  - Sex-based differential regulation of oxidative stress in the vasculature by
      nitric oxide.
AB  - BACKGROUND: Nitric oxide ((*)NO) is more effective at inhibiting neointimal
      hyperplasia following arterial injury in male versus female rodents, though the
      etiology is unclear. Given that superoxide (O2(*-)) regulates cellular
      proliferation, and (*)NO regulates superoxide dismutase-1 (SOD-1) in the
      vasculature, we hypothesized that (*)NO differentially regulates SOD-1 based on
      sex. MATERIALS AND METHODS: Male and female vascular smooth muscle cells (VSMC)
      were harvested from the aortae of Sprague-Dawley rats. O2(*-) levels were
      quantified by electron paramagnetic resonance (EPR) and HPLC. sod-1 gene
      expression was assayed by qPCR. SOD-1, SOD-2, and catalase protein levels were
      detected by Western blot. SOD-1 activity was measured via colorimetric assay. The
      rat carotid artery injury model was performed on Sprague-Dawley rats +/-(*)NO
      treatment and SOD-1 protein levels were examined by Western blot. RESULTS: In
      vitro, male VSMC have higher O2(*-) levels and lower SOD - 1 activity at baseline
      compared to female VSMC (P < 0.05). (*)NO decreased O2(*-) levels and increased
      SOD - 1 activity in male (P<0.05) but not female VSMC. (*)NO also increased sod-
      1 gene expression and SOD - 1 protein levels in male (P<0.05) but not female
      VSMC. In vivo, SOD-1 levels were 3.7-fold higher in female versus male carotid
      arteries at baseline. After injury, SOD-1 levels decreased in both sexes, but
      (*)NO increased SOD-1 levels 3-fold above controls in males, but returned to
      baseline in females. CONCLUSIONS: Our results provide evidence that regulation of
      the redox environment at baseline and following exposure to (*)NO is sex
      dependent in the vasculature. These data suggest that sex-based differential
      redox regulation may be one mechanism by which (*)NO is more effective at
      inhibiting neointimal hyperplasia in male versus female rodents.

PMID- 25617802
TI  - Autophagy in lung disease pathogenesis and therapeutics.
AB  - Autophagy, a cellular pathway for the degradation of damaged organelles and
      proteins, has gained increasing importance in human pulmonary diseases, both as a
      modulator of pathogenesis and as a potential therapeutic target. In this pathway,
      cytosolic cargos are sequestered into autophagosomes, which are delivered to the
      lysosomes where they are enzymatically degraded and then recycled as metabolic
      precursors. Autophagy exerts an important effector function in the regulation of
      inflammation, and immune system functions. Selective pathways for autophagic
      degradation of cargoes may have variable significance in disease pathogenesis.
      Among these, the autophagic clearance of bacteria (xenophagy) may represent a
      crucial host defense mechanism in the pathogenesis of sepsis and inflammatory
      diseases. Our recent studies indicate that the autophagic clearance of
      mitochondria, a potentially protective program, may aggravate the pathogenesis of
      chronic obstructive pulmonary disease by activating cell death programs. We
      report similar findings with respect to the autophagic clearance of cilia
      components, which can contribute to airways dysfunction in chronic lung disease.
      In certain diseases such as pulmonary hypertension, autophagy may confer
      protection by modulating proliferation and cell death. In other disorders, such
      as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may
      contribute to pathogenesis. In lung cancer, autophagy has multiple consequences
      by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting
      tumor cell survival. In this review we highlight the multiple functions of
      autophagy and its selective autophagy subtypes that may be of significance to the
      pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

PMID- 25617804
TI  - Photoreactive interpenetrating network of hyaluronic acid and Puramatrix as a
      selectively tunable scaffold for neurite growth.
AB  - The reconstruction of soft tissue, such as that which is found in the nervous
      system, is governed by the mechanical cues of the growth microenvironment. The
      complexity of the nervous system, particularly in cases of nerve repair and
      reconstruction, necessitates the development of facile high-throughput
      investigational tools. This study assesses the hypothesis that a mechanically
      tunable photoreactive interpenetrating network (IPN) of hyaluronic acid and
      Puramatrix can be manipulated in order to demonstrate that 3-D environmental
      stiffness influences neurite growth and proliferation. For these studies we
      employed photocrosslinkable glycidyl methacrylate hyaluronic acid (GMHA) and
      Puramatrix, a self-assembling peptide scaffold, leading to a structurally
      adjustable IPN system. Our in vitro model provides us with a simple, reproducible
      environment to generate different properties in a single specimen. Mechanically
      manipulated IPN systems with different degrees of methacrylation were fabricated
      using a dynamic mask projection photolithography apparatus and characterized. To
      gauge the impact of IPN stiffness on neurite outgrowth, dorsal root ganglia (DRG)
      explants were cultured in the hydrogels. We found that neurite outgrowth in 3-D
      was more likely to happen in an environment with a lesser degree of
      methacrylation, which corresponded to structures that were more compliant and
      more porous. Overall, tuning the mechanical behavior of our IPN systems led to
      statistically significant (p<0.05) differences in cellular growth and extension
      that warrants further investigations. 

PMID- 25617805
TI  - Therapeutic-designed electrospun bone scaffolds: mesoporous bioactive
      nanocarriers in hollow fiber composites to sequentially deliver dual growth
      factors.
AB  - A novel therapeutic design of nanofibrous scaffolds, holding a capacity to load
      and deliver dual growth factors, that targets bone regeneration is proposed.
      Mesoporous bioactive glass nanospheres (MBNs) were used as bioactive nanocarriers
      for long-term delivery of the osteogenic enhancer fibroblast growth factor 18
      (FGF18). Furthermore, a core-shell structure of a biopolymer fiber made of
      polyethylene oxide/polycaprolactone was introduced to load FGF2, another type of
      cell proliferative and angiogenic growth factor, safely within the core while
      releasing it more rapidly than FGF18. The prepared MBNs showed enlarged mesopores
      of about 7 nm, with a large surface area and pore volume. The protein-loading
      capacity of MBNs was as high as 13% when tested using cytochrome C, a model
      protein. The protein-loaded MBNs were smoothly incorporated within the core of
      the fiber by electrospinning, while preserving a fibrous morphology. The
      incorporation of MBNs significantly increased the apatite-forming ability and
      mechanical properties of the core-shell fibers. The possibility of sequential
      delivery of two experimental growth factors, FGF2 and FGF18, incorporated either
      within the core-shell fiber (FGF2) or within MBNs (FGF18), was demonstrated by
      the use of cytochrome C. In vitro studies using rat mesenchymal stem cells
      demonstrated the effects of the FGF2-FGF18 loadings: significant stimulation of
      cell proliferation as well as the induction of alkaline phosphate activity and
      cellular mineralization. An in vivo study performed on rat calvarium defects for
      6 weeks demonstrated that FGF2-FGF18-loaded fiber scaffolds had significantly
      higher bone-forming ability, in terms of bone volume and density. The current
      design utilizing novel MBN nanocarriers with a core-shell structure aims to
      release two types of growth factors, FGF2 and FGF18, in a sequential manner, and
      is considered to provide a promising therapeutic scaffold platform that is
      effective for bone regeneration.

PMID- 25617807
TI  - Risk Factors for Steroid-Refractory Acute Graft-versus-Host Disease after
      Allogeneic Stem Cell Transplantation from Matched Related or Unrelated Donors.
AB  - We performed a retrospective study to identify pretransplantation risk factors
      for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after
      allogeneic stem cell transplantation from matched donors in 630 adult patients
      who underwent transplantation at our center between 2000 and 2012. The cumulative
      incidence (CI) of SR aGVHD was 11.3% +/- 2.3%. The identified independent risk
      factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female
      donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte
      globulin (HR, 2.02; P = .005). Three risk groups were defined according to the
      presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5%
      +/- 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% +/- 1.6% in the
      intermediate-risk group (1 risk factor, n = 323), and 19.3% +/- 2.9% in the high
      risk group (2 or 3 risk factors, n = 192). Our study suggests that
      pretransplantation characteristics might help identify patients at high risk for
      SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in
      those patients.

PMID- 25617806
TI  - Role of Donor Activating KIR-HLA Ligand-Mediated NK Cell Education Status in
      Control of Malignancy in Hematopoietic Cell Transplant Recipients.
AB  - Some cancers treated with allogeneic hematopoietic stem cell transplantation
      (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends
      on activating and inhibitory receptors and is modified by NK education/licensing
      effect and mediated by coexpression of inhibitory killer-cell immunoglobulin-like
      receptor (KIR) and its corresponding HLA I ligand. We assessed activating KIR
      (aKIR)-based HLA I-dependent education capacity in donor NKs in 285 patients with
      hematological malignancies after HSCT from unrelated donors. We found
      significantly adverse progression-free survival (PFS) and time to progression
      (TTP) in patients who received transplant from donors with NKs educated by
      C1:KIR2DS2/3, C2:KIR2DS1, or Bw4:KIR3DS1 pairs (for PFS: hazard ratio [HR], 1.70;
      P = .0020, Pcorr = .0039; HR, 1.54; P = .020, Pcorr = .039; HR, 1.51; P = .020,
      Pcorr = .040; and for TTP: HR, 1.82; P = .049, Pcorr = .096; HR, 1.72; P = .096,
      Pcorr = .18; and HR, 1.65; P = .11, Pcorr = .20, respectively). Reduced PFS and
      TTP were significantly dependent on the number of aKIR-based education systems in
      donors (HR, 1.36; P = .00031, Pcorr = .00062; and HR, 1.43; P = .019, Pcorr =
      .038). Furthermore, the PFS and TTP were strongly adverse in patients with
      missing HLA ligand cognate with educating aKIR-HLA pair in donor (HR, 3.25; P =
      .00022, Pcorr = .00045; and HR, 3.82; P = .027, Pcorr = .054). Together, these
      data suggest important qualitative and quantitative role of donor NK education
      via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection
      of transplant donors with high numbers of aKIR-HLA-based education systems,
      especially for recipients with missing cognate ligand, is advisable.

PMID- 25617808
TI  - Using fludarabine to reduce exposure to alkylating agents in children with sickle
      cell disease receiving busulfan, cyclophosphamide, and antithymocyte globulin
      transplant conditioning: results of a dose de-escalation trial.
AB  - High-dose busulfan, cyclophosphamide, and antithymocyte globulin (BU-CY-ATG) is
      the most commonly used conditioning regimen in HLA-matched related hematopoietic
      cell transplantation for children with sickle cell disease. Disease-free survival
      with this regimen is now approximately 95%; however, it produces significant
      morbidity. We hypothesized we could create a less toxic regimen by adding
      fludarabine (FLU) to BU-CY-ATG and reduce the dosages of busulfan and
      cyclophosphamide. We conducted a multicenter dose de-escalation trial with the
      objective of decreasing the doses of busulfan and cyclophosphamide by 50% and
      55%, respectively. Using day +28 donor-predominant chimerism as a surrogate
      endpoint for sustained engraftment, we completed the first 2 of 4 planned levels,
      enrolling 6 patients at each and reducing the total dose of cyclophosphamide from
      200 mg/kg to 90 mg/kg. On the third level, which involved a reduction of i.v.
      busulfan from 12.8 mg/kg to 9.6 mg/kg, the first 2 patients had host-predominant
      T cell chimerism, which triggered trial-stopping rules. All 14 patients survive
      disease-free. No patients suffered severe regimen-related toxicity. Our results
      suggest BU-FLU-CY-ATG using lower dose CY could be a less toxic yet effective
      regimen. Further evaluation of this regimen in a full-scale clinical trial is
      warranted.

PMID- 25617809
TI  - Developmental toxicity in rats of a hemoglobin-based oxygen carrier results from
      impeded function of the inverted visceral yolk sac.
AB  - HBOC-201 is a bovine-derived, cross-linked, and stabilized hemoglobin (250kDa) in
      physiological saline. Daily intravenous infusions of HBOC (1.95, 3.90, or
      5.85g/kg/day) during gestational days (GDs) 6-18 in Sprague-Dawley rats caused
      fetal mortality, reduced birth weight, and malformations. Subsequent single-day
      infusions (5.85g/kg/day) showed that developmental toxicity was limited to GDs 7
      9 when histiotrophic nutrition via the inverted visceral yolk sac (invVYS) is
      essential. Histiotrophic nutrition is receptor-mediated endocytosis of bulk
      maternal proteins and subsequent lysosomal degradation providing amino acids and
      other nutrients for embryonic growth. Controls for protein content, oncotic
      properties, and hemoglobin content indicated that toxicity was due to hemoglobin.
      Rat whole embryo cultures verified HBOC interference with invVYS transport
      capacity and resultant deficient embryonic nutrition. These mechanisms of action
      are not expected to impact human development based on differences in VYS
      morphology and function, although a complete understanding of early human
      embryonic nutrition is lacking. 

PMID- 25617810
TI  - Protective effect of olive oil and colocynth oil against cadmium-induced
      oxidative stress in the liver of Wistar rats.
AB  - Cadmium (Cd) is one of the most common heavy metal pollutants. It is accumulated
      particularly in liver and kidney. The present study examined the possible
      protective effect of olive oil and colocynth oil consumption against Cd-induced
      damage on plasma lipids and stress biochemical parameters of rats. Male albino
      Wistar rats were randomly divided into 6 groups of 5 animals each and treated
      orally with Cd (50 mg/l), olive oil and colocynth oil (4%) alone or in
      combination with cadmium for 8 weeks. It was shown that Cd exposure induced
      significant increases in the activities of serum alanine aminotransferase,
      aspartate aminotransferase, lipid peroxidation levels (MDA) and protein carbonyl
      contents in exposed groups of rats compared to control group while the
      antioxidant enzymes, reduced glutathione and vitamins (C, A and E) were
      significantly decreased. Co-treatment with olive oil or colocynth oil
      significantly improved the oxidative damage induced by Cd. The antioxidant
      potential in plasma and liver were markedly restored with a significant decline
      in MDA levels and activity of transaminases. In conclusion, these results suggest
      that olive oil or colocynth oil consumption could protect the rat liver against
      Cd-induced injury by increasing the activities of antioxidant enzymes and
      reducing oxidative stress. 

PMID- 25617811
TI  - Chemical allergens stimulate human epidermal keratinocytes to produce
      lymphangiogenic vascular endothelial growth factor.
AB  - Allergic contact dermatitis (ACD) is a cell-mediated immune response that
      involves skin sensitization in response to contact with various allergens.
      Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization
      process. Epidermal keratinocytes can produce vascular endothelial growth factor
      (VEGF) in response to UV irradiation and during wound healing. However, the
      effect of haptenic chemical allergens on the VEGF production of human
      keratinocytes, which is the primary contact site of toxic allergens, has not been
      thoroughly researched. We systematically investigated whether immune-regulatory
      cytokines and chemical allergens would lead to the production of VEGF in normal
      human keratinocytes (NHKs) in culture. VEGF production significantly increased
      when NHKs were treated with IFNgamma, IL-1alpha, IL-4, IL-6, IL-17A, IL-22 or
      TNFalpha. Among the human sensitizers listed in the OECD Test Guideline (TG) 429,
      we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2
      mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and
      nickel chloride all significantly upregulated VEGF production in NHKs. In
      addition, common human haptenic allergens such as avobenzone, formaldehyde and
      urushiol, also induced the keratinocyte-derived VEGF production. VEGF
      upregulation by pro-inflammatory stimuli, IFNgamma, DNCB or formaldehyde is
      preceded by the production of IL-8, an acute inflammatory phase cytokine.
      Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs
      were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A
      and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF
      upregulation is mainly due to the increase in lymphangiogenic VEGF-C
      transcription in NHKs. These results suggest that keratinocyte-derived VEGF may
      regulate the lymphangiogenic process during the skin sensitization process of
      ACD. 

PMID- 25617812
TI  - Conditioned placebo analgesia persists when subjects know they are receiving a
      placebo.
AB  - Belief in the effectiveness of a placebo treatment is widely thought to be
      critical for placebo analgesia. Many types of placebo responses--even those that
      depend on conditioning--appear to be mediated by expectations that are
      strengthened as treatment cues are reinforced with positive outcomes. However,
      placebo effects may occur even when participants are aware they are receiving a
      placebo. To address the question of whether conditioned placebo analgesia can
      persist in the absence of expectations, we studied the effects of long (4 days)
      versus short (1 day) conditioning to a placebo treatment. After an initial
      placebo test, a "reveal" manipulation convincingly demonstrated to participants
      that they had never received an active drug. Placebo analgesia persisted after
      the reveal in the long conditioning group only. These findings suggest that
      reinforcing treatment cues with positive outcomes can create placebo effects that
      are independent of reported expectations for pain relief. PERSPECTIVE: This
      article demonstrates a form of placebo analgesia that relies on prior
      conditioning rather than current expected pain relief. This highlights the
      importance of prior experience on pain relief and offers insight into the
      variability of placebo effects across individuals.

PMID- 25617813
TI  - Cryo-electron tomography of plunge-frozen whole bacteria and vitreous sections to
      analyze the recently described bacterial cytoplasmic structure, the Stack.
AB  - Cryo-electron tomography (CET) of plunge-frozen whole bacteria and vitreous
      sections (CETOVIS) were used to revise and expand the structural knowledge of the
      "Stack", a recently described cytoplasmic structure in the Antarctic bacterium
      Pseudomonas deceptionensis M1(T). The advantages of both techniques can be
      complementarily combined to obtain more reliable insights into cells and their
      components with three-dimensional imaging at different resolutions. Cryo-electron
      microscopy (Cryo-EM) and CET of frozen-hydrated P. deceptionensis M1(T) cells
      confirmed that Stacks are found at different locations within the cell cytoplasm,
      in variable number, separately or grouped together, very close to the plasma
      membrane (PM) and oriented at different angles (from 35 degrees  to 90 degrees )
      to the PM, thus establishing that they were not artifacts of the previous sample
      preparation methods. CET of plunge-frozen whole bacteria and vitreous sections
      verified that each Stack consisted of a pile of oval disc-like subunits, each
      disc being surrounded by a lipid bilayer membrane and separated from each other
      by a constant distance with a mean value of 5.2+/-1.3nm. FM4-64 staining and
      confocal microscopy corroborated the lipid nature of the membrane of the Stacked
      discs. Stacks did not appear to be invaginations of the PM because no continuity
      between both membranes was visible when whole bacteria were analyzed. We are
      still far from deciphering the function of these new structures, but a first
      experimental attempt links the Stacks with a given phase of the cell replication
      process. 

PMID- 25617814
TI  - A controlled examination of two coping skills for daily alcohol use and PTSD
      symptom severity among dually diagnosed individuals.
AB  - Investigations of targeted coping skills could help guide initial treatment
      decisions for individuals with co-occurring posttraumatic stress disorder (PTSD)
      and alcohol dependence (AD) who often endorse worse coping skills than those with
      AD but not PTSD. Although improvement in coping skills is associated with
      enhanced alcohol use outcomes, no study has evaluated the utility of teaching
      specific coping skills in the context of comorbid PTSD/AD. We compared the
      effects of teaching two coping skills (cognitive restructuring [CR] and
      experiential acceptance [EA]) or an attention control condition on drinking and
      PTSD symptoms among 78 men and women with comorbid PTSD/AD during a 5-week daily
      follow-up assessment. Both CR and EA skills were associated with decreased
      drinking compared to control, and that change in drinking over time did not
      significantly differ between those who received CR and EA. Individuals who
      received CR skills, however, consumed less alcohol on a given day than those who
      received EA skills. Neither CR nor EA was associated with a decrease in PTSD
      symptom severity. These results provide preliminary support for clinicians to
      prioritize CR and EA skills during initial treatment sessions when working with
      individuals with PTSD/AD, and offer ideas for continued investigation and
      intervention refinement. 

PMID- 25617815
TI  - Twenty-year brain magnetic resonance imaging follow-up study in Systemic Lupus
      Erythematosus: Factors associated with accrual of damage and central nervous
      system involvement.
AB  - To evaluate the long-term progression of cerebral MRI abnormalities in patients
      with longstanding SLE, 30 patients (age 53.5 +/- 11.3) underwent brain MRI at
      baseline (b-MRI) and after 19.4 +/- 3.7 years of follow-up (fu-MRI). Two
      neuroradiologists visually analyzed the MRIs comparing: 1) white matter
      hyperintensities (WMHIs), 2) cerebral volume, and 3) parenchymal defects; these
      outcomes were also built in a modified MRI scoring system (mMSS) to estimate the
      cumulative parenchymal damage. The independent risk factors for accrual of MRI
      brain damage, as well as the association between MRI abnormalities and the
      development of new neuropsychiatric (NP) manifestations classified according to
      the 1999 ACR case definition were also analyzed. Twenty-three patients (76.7%)
      showed worsening of mMSS; 19 (63.3%) had increased number and volume of WMHIs, 8
      (26.7%) had significant cerebral volume loss, and 6 (20%) showed new ischemic
      parenchymal lesions. Only 6 patients had normal MRI. Antimalarial agents
      (p=0.006; OR 0.08) were protective against worsening of WMHIs. High cumulative
      dose of corticosteroids (p=0.026; OR 8.8) and dyslipidemia (p=0.044; OR 10.1)
      were associated with increased mMSS and cerebral volume loss, respectively.
      Higher mMSS score at baseline was independently associated with worsening of
      WMHIs (p=0.001; OR 5.7) and development of new NP events (p=0.019; OR 2.0);
      higher load of deep WMHIs at b-MRI (p=0.018; OR 2.0) was independently associated
      with stroke risk. This study shows that MRI brain damage in SLE patients
      progresses independently from NP involvement as effect of potentially modifiable
      risk factors and it is associated with increased risk of new NP events.

PMID- 25617816
TI  - Guidance for the management of patients with latent tuberculosis infection
      requiring biologic therapy in rheumatology and dermatology clinical practice.
AB  - Since the introduction of biologics for the treatment of rheumatoid arthritis
      (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and psoriasis (Pso)
      an increased risk of tuberculosis (TB) reactivation in patients with latent
      tuberculosis infection (LTBI) has been recorded for anti-TNF agents, while a low
      or absent risk is associated with the non-anti-TNF targeted biologics. To reduce
      this risk several recommendation sets have been published over time, but in most
      of them the host-related risk, and the predisposing role to TB reactivation
      exerted by corticosteroids and by the traditional disease-modifying anti
      rheumatic drugs has not been adequately addressed. Moreover, the management of
      the underlying disease, and the timing of biologic restarting in patients with TB
      occurrence have been rarely indicated. A multidisciplinary expert panel, the
      Italian multidisciplinary task force for screening of tuberculosis before and
      during biologic therapy (SAFEBIO), was constituted, and through a review of the
      literature, an evidence-based guidance for LTBI detection, identification of the
      individualized level of risk of TB reactivation, and practical management of
      patients with TB occurrence was formulated. The literature review confirmed a
      higher TB risk associated with monoclonal anti-TNF agents, a low risk for soluble
      receptor etanercept, and a low or absent risk for non-anti-TNF targeted
      biologics. Considering the TB reactivation risk associated with host demographic
      and clinical features, and previous or current non-biologic therapies, a low,
      intermediate, or high TB reactivation risk in the single patient was identified,
      thus driving the safest biologic choice. Moreover, based on the underlying
      disease activity measurement and the different TB risk associated with non
      biologic and biologic therapies, practical indications for the treatment of RA,
      PsA, AS, and Pso in patients with TB occurrence, as well as the safest timing of
      biologic restarting, were provided.

PMID- 25617817
TI  - Atypical presentations of bullous pemphigoid: Clinical and immunopathological
      aspects.
AB  - Bullous pemphigoid may occur in extremely variegated manners, misleading even
      experienced dermatologists. Indeed the type and/or distribution of lesions may be
      unusual. Furthermore, there may be an atypical demographic profile of patients, a
      different clinical course and a different responsiveness to therapy. Up to 20% of
      the cases the onset is characterized by a non-bullous phase, lasting weeks,
      months or in particular cases remaining the only manifestation of the disease.
      During this early phase lesions are generally pruritic erythematous, eczematous
      or urticarial; however, lesions may also resemble polycyclic, targetoid, nodular
      or lichenoid lesions. These atypical lesions may also coexist with typical
      bullae. Other atypical presentations include a vesicular eruption and an
      erythroderma. Manifestations in children differ from adult forms, presenting an
      exclusive genital involvement in 50% of cases or a preponderant involvement of
      the face, the palms and the soles. Rarely bullous pemphigoid is confined to
      certain body areas, due to particular triggering factors or to a lower disease
      activity. Therefore, the need to formulate universally recognized diagnostic
      criteria is increasingly evident, especially for atypical bullous pemphigoid.
      Direct immunofluorescence of perilesional skin and detection of circulating
      autoantibodies are mandatory in the diagnosis, especially when the clinical
      presentation is doubtful.

PMID- 25617818
TI  - The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid
      syndrome: Data from a European multicenter retrospective study.
AB  - In European multicenter study, we aimed to describe the real-life
      hydroxychloroquine use in APS patients during pregnancy and determine its benefit
      in refractory obstetrical APS. We analyzed the outcome of pregnancies treated by
      hydroxychloroquine in patients with APS or asymptomatic antiphospholipid (aPL)
      antibodies carriers. Thirty patients with APS with 35 pregnancies treated by
      hydroxychloroquine were analyzed. Comparing the outcome of pregnancies treated by
      the addition of hydroxychloroquine to previous pregnancies under the conventional
      treatment, pregnancy losses decreased from 81% to 19% (p<0.05), without
      differences in the associated treatments. The univariate analysis showed that the
      previous intrauterine deaths and higher hydroxychloroquine amount (400mg per day)
      were the factors associated with pregnancy outcome. Considering 14 patients with
      previous refractory obstetrical APS (n=5 with obstetrical and thrombotic primary
      APS and n=9 with purely obstetrical APS), all with previous pregnancy losses
      under treatment (aspirin with LMWH in 11 cases and LMWH in 3 cases), the addition
      of hydroxychloroquine resulted in live born babies in 11/14 (78%) cases (p<0.05).
      Our study shows the benefit of hydroxychloroquine addition in patients with
      refractory obstetrical APS and raises the need of prospective studies to confirm
      our preliminary study.

PMID- 25617819
TI  - Seizing the clinical presentation in adult onset Still's disease. An extensive
      literature review.
AB  - Adult onset Still's disease is an inflammatory disorder with a wide clinical
      presentation ranging from arthralgia and arthritis to rash and high-grade fever.
      Etiology of this rare disorder remains a mystery. We present two cases at the
      extreme ends of clinical presentation diagnosed with AOSD along with literature
      review for the same. Case one was self limiting, requiring only NSAIDS as
      treatment. The other was an unusual central nervous system manifestation of
      repeated seizures that were only responsive to pulse dose of methylprednisolone.
      Both met Yamaguchi criteria for adult onset Still's disease.

PMID- 25617820
TI  - Neural indicators of emotion regulation via acceptance vs reappraisal in remitted
      major depressive disorder.
AB  - Mood disorders are characterized by impaired emotion regulation abilities,
      reflected in alterations in frontolimbic brain functioning during regulation.
      However, little is known about differences in brain function when comparing
      regulatory strategies. Reappraisal and emotional acceptance are effective in
      downregulating negative affect, and are components of effective depression
      psychotherapies. Investigating neural mechanisms of reappraisal vs emotional
      acceptance in remitted major depressive disorder (rMDD) may yield novel
      mechanistic insights into depression risk and prevention. Thirty-seven
      individuals (18 rMDD, 19 controls) were assessed during a functional magnetic
      resonance imaging task requiring reappraisal, emotional acceptance or no explicit
      regulation while viewing sad images. Lower negative affect was reported following
      reappraisal than acceptance, and was lower following acceptance than no explicit
      regulation. In controls, the acceptance > reappraisal contrast revealed greater
      activation in left insular cortex and right prefrontal gyrus, and less activation
      in several other prefrontal regions. Compared with controls, the rMDD group had
      greater paracingulate and right midfrontal gyrus (BA 8) activation during
      reappraisal relative to acceptance. Compared with reappraisal, acceptance is
      associated with activation in regions linked to somatic and emotion awareness,
      although this activation is associated with less reduction in negative affect.
      Additionally, a history of MDD moderated these effects. 

PMID- 25617821
TI  - Involvement of non-NMDA glutamate receptors of the hypothalamic paraventricular
      nucleus in the cardiovascular response to the microinjection of noradrenaline
      into the dorsal periaqueductal gray area of rats.
AB  - The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular
      modulation. In a previous study, we showed that noradrenaline (NA) microinjected
      into the dPAG caused a vasopressin-mediated pressor response, involving a relay
      in the hypothalamic paraventricular nucleus (PVN). In the present study, we
      evaluated the involvement of ionotropic glutamate receptors within the PVN in the
      cardiovascular response to NA microinjection into the dPAG of unanesthetized
      rats. Microinjection of the selective NMDA glutamate receptor antagonist LY235959
      (2nmol/100nL) unilaterally into the PVN did not affect the cardiovascular
      response evoked by microinjection of NA (15nmol/50nL) into the dPAG. On the other
      hand, unilateral PVN pretreatment with the non-NMDA glutamate receptor antagonist
      NBQX (2nmol/100nL) significantly reduced the pressor and cardiac response caused
      by microinjection of NA into the dPAG. In addition, bilateral PVN pretreatment
      with NBQX (2nmol/100nL) blocked the cardiovascular response to NA injected into
      the dPAG. In conclusion, the present results suggest that bilateral PVN
      activation of non-NMDA glutamate receptors mediates the vasopressin-related
      cardiovascular response to the microinjection of NA into the dPAG. 

PMID- 25617822
TI  - Neuroprotective effects of cilostazol are mediated by multiple mechanisms in a
      mouse model of permanent focal ischemia.
AB  - The phosphodiesterase (PDE) 3 inhibitor cilostazol, used as an anti-platelet
      drug, reportedly can also ameliorate ischemic brain injury. Here, we investigated
      the effects of cilostazol in a permanent focal ischemia mice model. Male Balb/c
      mice were subjected to permanent middle cerebral artery occlusion. Mice were then
      treated with either cilostazol (10 or 20mg/kg) or vehicle administered at 30min
      and 24h post-ischemia, and infarct volumes were assessed at 48h post-ischemia.
      Mice treated with 20mg/kg of cilostazol or vehicle were sacrificed at 6h or 24h
      post-ischemia and immunohistochemistry was used for brain sections. Treatment
      with 20mg/kg of cilostazol significantly reduced infarct volumes to 70.1% of
      those with vehicle treatment. Immunohistochemistry results for 8
      hydroxydeoxyguanosine (OHdG) expression showed that some neurons underwent
      oxidative stress around the ischemic boundary zone at 6h post-ischemia.
      Cilostazol treatment significantly reduced the percentage of 8-OHdG-positive
      neurons (65.8+/-33.5% with vehicle and 21.3+/-9.9% with cilostazol). Moreover,
      NADPH oxidase (NOX) 2-positive neurons were significantly reduced with cilostazol
      treatment. In contrast, immunohistochemistry results for phosphorylated cyclic
      AMP response element binding protein (pCREB) showed that there were significantly
      more pCREB-positive neurons around the ischemic boundary zone of cilostazol
      treated mice than in those of vehicle-treated mice at 24h post-ischemia. These
      results suggested that cilostazol might have multiple mechanisms of action to
      ameliorate ischemic tissue damage, by attenuating oxidative stress mediated by
      suppressing NOX2 expression by ischemic neurons and an anti-apoptotic effect
      mediated through the pCREB pathway. 

PMID- 25617823
TI  - An inexpensive replacement for dry ice in the laboratory.
AB  - A reusable inexpensive replacement for dry ice in laboratory use is presented.
      Commercially available small pellets of stone or metal can be stored in a -80 
      degrees C freezer and used for quickly freezing small samples with a freezing
      rate that is actually somewhat faster than with dry ice itself. Following use,
      the material is returned to the freezer to re-chill until the next usage.

PMID- 25617824
TI  - Structure and receptor binding preferences of recombinant human A(H3N2) virus
      hemagglutinins.
AB  - A(H3N2) influenza viruses have circulated in humans since 1968, and antigenic
      drift of the hemagglutinin (HA) protein continues to be a driving force that
      allows the virus to escape the human immune response. Since the major antigenic
      sites of the HA overlap into the receptor binding site (RBS) of the molecule, the
      virus constantly struggles to effectively adapt to host immune responses, without
      compromising its functionality. Here, we have structurally assessed the evolution
      of the A(H3N2) virus HA RBS, using an established recombinant expression system.
      Glycan binding specificities of nineteen A(H3N2) influenza virus HAs, each a
      component of the seasonal influenza vaccine between 1968 and 2012, were analyzed.
      Results suggest that while its receptor-binding site has evolved from one that
      can bind a broad range of human receptor analogs to one with a more restricted
      binding profile for longer glycans, the virus continues to circulate and transmit
      efficiently among humans.

PMID- 25617825
TI  - Adipose-derived stromal vascular fraction cells isolated from old animals exhibit
      reduced capacity to support the formation of microvascular networks.
AB  - Adipose-derived regenerative and stem cells, defined collectively as the stromal
      vascular fraction (SVF), support the formation of neovascular networks at the
      site of implantation. The effect of advancing age on SVF cell population
      effectiveness towards stimulated neovascularization was evaluated. METHODS: SVF
      was enzymatically isolated from adipose of young (ySVF, 4 months) or old (oSVF,
      24 months) Fisher-344 rats, combined with type I collagen and polymerized.
      Encapsulated SVF was implanted subcutaneously into young Rag1 mice for two or
      four weeks. Angiogenic function of age-dependent SVF was also extensively
      evaluated in vitro using standard assays. RESULTS: In vitro studies indicated no
      difference in angiogenic function between ySVF and oSVF (viability,
      proliferation, migration, and tube-formation). At two weeks post-implantation,
      there was no age-related difference in percent apoptosis in explanted constructs.
      By four weeks post-implantation, oSVF implants displayed 36% less total
      vessels/mm(2), 43% less perfused vessels/mm(2), and exhibited greater percent
      apoptosis compared to ySVF (n >= 12). Blocking thrombospondin-1 (Thbs-1), a
      protein found to be highly expressed in oSVF but not ySVF, increased the percent
      of perfused vascular volume and vessel diameters in oSVF constructs after two
      weeks compared to oSVF implants treated with control antibody. CONCLUSIONS:
      Advancing donor age reduces the potential of adipose-derived SVF to derive a
      mature microcirculation, but does not hinder initial angiogenesis. However,
      modulation of Thbs-1 may improve this outcome. This data suggests that greater
      pruning, dysfunctional structural adaptation and/or poor maturation with
      initiation of blood flow may occur in oSVF.

PMID- 25617826
TI  - Proper name anomia with preserved lexical and semantic knowledge after left
      anterior temporal lesion: a two-way convergence defect.
AB  - This article describes the case of a patient who, following herpes simplex
      encephalitis (HSE), retained the ability to access rich conceptual semantic
      information for familiar people whom he was no longer able to name. Moreover,
      this patient presented the very rare combination of name production and name
      comprehension deficits for different categories of proper names (persons and
      acronyms). Indeed, besides his difficulty to retrieve proper names, SL presented
      a severe deficit in understanding and identifying them. However, he was still
      able to recognize proper names on familiarity decision, demonstrating that name
      forms themselves were intact. We interpret SL's deficit as a rare form of two-way
      lexico-semantic disconnection, in which intact lexical knowledge is disconnected
      from semantic knowledge and face units. We suggest that this disconnection
      reflects the role of the left anterior temporal lobe in binding together
      different types of knowledge and supports the classical convergence-zones
      framework (e.g., Damasio, 1989) rather than the amodal semantic hub theory (e.g.,
      Patterson, Nestor, & Rogers, 2007). 

PMID- 25617827
TI  - The widespread role of non-enzymatic reactions in cellular metabolism.
AB  - Enzymes shape cellular metabolism, are regulated, fast, and for most cases
      specific. Enzymes do not however prevent the parallel occurrence of non-enzymatic
      reactions. Non-enzymatic reactions were important for the evolution of metabolic
      pathways, but are retained as part of the modern metabolic network. They divide
      into unspecific chemical reactivity and specific reactions that occur either
      exclusively non-enzymatically as part of the metabolic network, or in parallel to
      existing enzyme functions. Non-enzymatic reactions resemble catalytic mechanisms
      as found in all major enzyme classes and occur spontaneously, small molecule
      (e.g. metal-) catalyzed or light-induced. The frequent occurrence of non
      enzymatic reactions impacts on stability and metabolic network structure, and has
      thus to be considered in the context of metabolic disease, network modeling,
      biotechnology and drug design. 

PMID- 25617828
TI  - Artificial hydrogenase: biomimetic approaches controlling active molecular
      catalysts.
AB  - Hydrogenase catalyses reversible transformation of H2 to H(+) using an active
      site which includes an iron or nickel atom. Synthetic model complexes and
      molecular catalysts inspired by nature have unveiled the structural and
      functional basis of the active site with remarkable accuracy and this has led to
      the discovery of active synthetic catalysts. To further improve the activity of
      such molecular catalysts, both the first and outer coordination spheres should be
      well-organized and harmonized for an efficient shuttling of H(+), electrons, and
      H2. This article reviews recent advances in the design and catalytic properties
      of artificial enzymes that mimic the hydrogenase active site and the outer
      coordination sphere in combination with a peptide or protein scaffold. 

PMID- 25617829
TI  - N-glycosylation and disulfide bonding affects GPRC6A receptor expression,
      function, and dimerization.
AB  - Investigation of post-translational modifications of receptor proteins is
      important for our understanding of receptor pharmacology and disease physiology.
      However, our knowledge about post-translational modifications of class C G
      protein-coupled receptors and how these modifications regulate expression and
      function is very limited. Herein, we show that the nutrient-sensing class C G
      protein-coupled receptor GPRC6A carries seven N-glycans and that one of these
      sites modulates surface expression whereas mutation of another site affects
      receptor function. GPRC6A has been speculated to form covalently linked dimers
      through cysteine disulfide linkage in the extracellular amino-terminal domain and
      here we show that GPRC6A indeed is a homodimer and that a disulfide bridge
      between the C131 residues is formed. 

PMID- 25617830
TI  - Chemical characteristics and mutagenic activity of PM2.5 at a site in the Indo
      Gangetic plain, India.
AB  - Airborne fine particulate matter PM2.5 was collected from May 2010 to December
      2012 at Agra, a semi-urban site in north-central India. PM2.5 samples were
      chemically characterized for 16 polycyclic aromatic hydrocarbons by gas
      chromatography. PM2.5 values varied between 8.4 and 300 ug m(-3) with 55% of the
      values exceeding the 24h average NAAQ (National Ambient Air Quality) standard of
      65 ug m(-3). Particle associated total PAHs ranged between 8.9 and 2,065 ng m(-3)
      with a mean value of 880.8 ng m(-3) during the sampling period, indicated an
      alarming level of pollution in Agra. Strong relationship was observed between
      PM2.5 and total PAHs (r=0.88), suggesting an increasing PAHs concentration with
      increasing PM2.5 mass. On a mass basis 3-ring and 4-ring compounds were dominant.
      Seasonal variation in mass concentration of PAHs was observed with high
      concentration in winter followed by post monsoon, summer and monsoon. This
      seasonal pattern could be attributed to differences in source strength and
      climatic conditions. PAHs concentration were also observed to be negatively
      correlated with the meteorological parameters i.e. temperature, solar radiation,
      relative humidity and wind speed. Molecular diagnostic ratios revealed vehicular
      emissions and combustion of wood and coal as the probable sources. The estimated
      carcinogenicity of PAHs in terms of benzo(a)pyrene toxic equivalency (B[a]PTEQ)
      was assessed and confirmed that benzo[a]pyrene was the dominant PAH contributor
      (3.64%). Health risk of adults and children by way of PAHs was assessed by
      estimating the lifetime average daily dose (LADD) and corresponding incremental
      lifetime cancer risk (ILCR) using USEPA guidelines. The assessed cancer risk
      (ILCR) was found to be within the acceptable range (10(-6)-10(-4)). The
      particulate samples indicated the presence of both base pair and frame shift
      mutagens using TA98 and TA100 strains of Salmonella typhimurium. Enhanced
      mutagenic response was observed in the presence of enzyme activation.

PMID- 25617831
TI  - Assessment of polyaniline nanoparticles toxicity and teratogenicity in aquatic
      environment using Rhinella arenarum model.
AB  - With the rapid growth of nanotechnology and the applications of nanoparticles,
      environmental exposure to these particles is increasing. However, their impact in
      human and environmental health is not well studied. Anurans, with life stage
      comprising embryos, tadpoles and adults, have an extremely permeable skin which
      makes them excellent indicators of environmental health. This study evaluated the
      acute toxicity effects of polyaniline nanoparticles (PANI-Np) in different
      dispersant on embryos and larvae of Rhinella arenarum. The results showed that
      LC50 of PANI-Np dispersed in polyvinylpyrrolidone (PVP) were 1,500 mg/L, while
      LC50 by PANI-Np dispersed in PVP+PNIPAM (polyN-isopropylacrilamide) showed a
      highest toxicity (1,170 mg/L). The embryo teratogenicity increased with
      increasing exposure concentration in both kinds of PANI-Np although in PANI-Np1,
      there is an increased teratogenic effect associated with the polymer stabilizer
      PVP.

PMID- 25617832
TI  - The influence of residual water on the solid-state properties of freeze-dried
      fibrinogen.
AB  - The purpose of this work was to investigate the influence of residual water in
      freeze-dried protein powders on the dissolution behavior of the solid-state
      proteins. To that end, six freeze-dried fibrinogen powder lots were stored at
      four levels of relative humidity and analyzed with regard to the particle size
      and shape, the specific surface area, the solid state of protein and the inner
      surface. Furthermore, the dissolution behavior of the powders was investigated.
      We clearly identified differences in the specific surface area, specific inner
      surface area, crystallinity, particle size and shape, which we were able to
      correlate to the dissolution behavior. These differences were triggered due to
      the different levels of residual moisture during two weeks of storage. Thus, we
      were able to show that the storage conditions have significant impact on the
      processing of pharmaceutical protein materials. 

PMID- 25617833
TI  - Human DNA helicase B functions in cellular homologous recombination and
      stimulates Rad51-mediated 5'-3' heteroduplex extension in vitro.
AB  - Homologous recombination is involved in the repair of DNA damage and collapsed
      replication fork, and is critical for the maintenance of genomic stability. Its
      process involves a network of proteins with different enzymatic activities. Human
      DNA helicase B (HDHB) is a robust 5'-3' DNA helicase which accumulates on
      chromatin in cells exposed to DNA damage. HDHB facilitates cellular recovery from
      replication stress, but its role in DNA damage response remains unclear. Here we
      report that HDHB silencing results in reduced sister chromatid exchange, impaired
      homologous recombination repair, and delayed RPA late-stage foci formation
      induced by ionizing radiation. Ectopically expressed HDHB colocalizes with Rad51,
      Rad52, RPA, and ssDNA. In vitro, HDHB stimulates Rad51-mediated heteroduplex
      extension in 5'-3' direction. A helicase-defective mutant HDHB failed to promote
      this reaction. Our studies implicate HDHB promotes homologous recombination in
      vivo and stimulates 5'-3' heteroduplex extension during Rad51-mediated strand
      exchange in vitro. 

PMID- 25617834
TI  - Integrin alphaIIbbeta3 transmembrane domain separation mediates bi-directional
      signaling across the plasma membrane.
AB  - Integrins play an essential role in hemostasis, thrombosis, and cell migration,
      and they transmit bidirectional signals. Transmembrane/cytoplasmic domains are
      hypothesized to associate in the resting integrins; whereas, ligand binding and
      intracellular activating signals induce transmembrane domain separation. However,
      how this conformational change affects integrin outside-in signaling and whether
      the alpha subunit cytoplasmic domain is important for this signaling remain
      elusive. Using Chinese Hamster Ovary (CHO) cells that stably expressed different
      integrin alphaIIbbeta3 constructs, we discovered that an alphaIIb cytoplasmic
      domain truncation led to integrin activation but not defective outside-in
      signaling. In contrast, preventing transmembrane domain separation abolished both
      inside-out and outside-in signaling regardless of removing the alphaIIb
      cytoplasmic tail. Truncation of the alphaIIb cytoplasmic tail did not obviously
      affect adhesion-induced outside-in signaling. Our research revealed that
      transmembrane domain separation is a downstream conformational change after the
      cytoplasmic domain dissociation in inside-out activation and indispensable for
      ligand-induced outside-in signaling. The result implicates that the beta TM helix
      rearrangement after dissociation is essential for integrin transmembrane
      signaling. Furthermore, we discovered that the PI3K/Akt pathway is not essential
      for cell spreading but spreading-induced Erk1/2 activation is PI3K dependent
      implicating requirement of the kinase for cell survival in outside-in signaling. 

PMID- 25617835
TI  - Carpal tunnel syndrome assessment with ultrasonography: value of inlet-to-outlet
      median nerve area ratio in patients versus healthy volunteers.
AB  - OBJECTIVE: To evaluate the diagnostic value of the Inlet-to-outlet median nerve
      area ratio (IOR) in patients with clinically and electrophysiologically confirmed
      carpal tunnel syndrome (CTS). METHODS: Forty-six wrists in 46 consecutive
      patients with clinical and electrodiagnostic evidence of CTS and forty-four
      wrists in 44 healthy volunteers were examined with ultrasonography. The cross
      sectional area (CSA) of the median nerve was measured at the carpal tunnel inlet
      (the level of scaphoid-pisiform) and outlet (the level of the hook of the
      hamate), and the IOR was calculated for each wrist. Ultrasonography and
      electrodiagnostic tests were performed under blinded conditions.
      Electrodiagnostic testing combined with clinical symptoms were considered to be
      the gold standard test. Receiver operating characteristic (ROC) curves were used
      to evaluate the diagnostic value between the inlet CSA and IOR. RESULTS: The
      study population included 16 men and 30 women (mean age, 45.3 years; range, 18-83
      years). The control population included 18 men and 26 women (mean age, 50.4
      years; range, 18-79 years). The mean inlet CSA was 8.7 mm2 in healthy controls
      and 14.6mm2 in CTS group (P<0.001). The mean IOR in healthy volunteers (1.0) was
      smaller than that in patients (1.6, P<0.001). Receiver operating characteristic
      analysis revealed a diagnostic advantage to using the IOR rather than the inlet
      CSA (P<0.01). An IOR cutoff value of >= 1.3 would yield 93% specificity and 91%
      sensitivity in the diagnosis of CTS. CONCLUSION: The IOR of median nerve area
      promises to be an effective means in the diagnosis of CTS. A large-scale,
      randomized controlled trial is required to determine how and when this parameter
      will be used.

PMID- 25617837
TI  - Intensive care unit capacity in low-income countries: a systematic review.
AB  - PURPOSE: Access to critical care is a crucial component of healthcare systems. In
      low-income countries, the burden of critical illness is substantial, but the
      capacity to provide care for critically ill patients in intensive care units
      (ICUs) is unknown. Our aim was to systematically review the published literature
      to estimate the current ICU capacity in low-income countries. METHODS: We
      searched 11 databases and included studies of any design, published 2004-August
      2014, with data on ICU capacity for pediatric and adult patients in 36 low-income
      countries (as defined by World Bank criteria; population 850 million). Neonatal,
      temporary, and military ICUs were excluded. We extracted data on ICU bed numbers,
      capacity for mechanical ventilation, and information about the hospital,
      including referral population size, public accessibility, and the source of
      funding. Analyses were descriptive. RESULTS: Of 1,759 citations, 43 studies from
      15 low-income countries met inclusion criteria. They described 36 individual ICUs
      in 31 cities, of which 16 had population greater than 500,000, and 14 were
      capital cities. The median annual ICU admission rate was 401 (IQR 234-711; 24
      ICUs with data) and median ICU size was 8 beds (IQR 5-10; 32 ICUs with data). The
      mean ratio of adult and pediatric ICU beds to hospital beds was 1.5% (SD 0.9%; 15
      hospitals with data). Nepal and Uganda, the only countries with national ICU bed
      data, had 16.7 and 1.0 ICU beds per million population, respectively. National
      data from other countries were not available. CONCLUSIONS: Low-income countries
      lack ICU beds, and more than 50% of these countries lack any published data on
      ICU capacity. Most ICUs in low-income countries are located in large referral
      hospitals in cities. A central database of ICU resources is required to evaluate
      health system performance, both within and between countries, and may help to
      develop related health policy.

PMID- 25617836
TI  - New light on the systematics of fungi associated with attine ant gardens and the
      description of Escovopsis kreiselii sp. nov.
AB  - Since the formal description of fungi in the genus Escovopsis in 1990, only a few
      studies have focused on the systematics of this group. For more than two decades,
      only two Escovopsis species were described; however, in 2013, three additional
      Escovopsis species were formally described along with the genus Escovopsioides,
      both found exclusively in attine ant gardens. During a survey for Escovopsis
      species in gardens of the lower attine ant Mycetophylax morschi in Brazil, we
      found four strains belonging to the pink-colored Escovopsis clade. Careful
      examination of these strains revealed significant morphological differences when
      compared to previously described species of Escovopsis and Escovopsioides. Based
      on the type of conidiogenesis (sympodial), as well as morphology of conidiogenous
      cells (percurrent), non-vesiculated conidiophores, and DNA sequences, we describe
      the four new strains as a new species, Escovopsis kreiselii sp. nov. Phylogenetic
      analyses using three nuclear markers (Large subunit RNA; translation elongation
      factor 1-alpha; and internal transcribed spacer) from the new strains as well as
      available sequences in public databases confirmed that all known fungi infecting
      attine ant gardens comprise a monophyletic group within the Hypocreaceae family,
      with very diverse morphological characteristics. Specifically, Escovopsis
      kreiselii is likely associated with gardens of lower-attine ants and its
      pathogenicity remains uncertain. 

PMID- 25617838
TI  - Genetic characterization of Shigella flexneri isolates in Guizhou Province,
      China.
AB  - Shigella flexneri is one of the major etiologic causes of shigellosis in Guizhou
      Province, China. However, the genetic characteristics of circulating isolates are
      unknown. Phenotypic and molecular profiles of 60 S. flexneri isolates recovered
      in Guizhou between 1972 to 1982 and 2008 to 2010 were determined. Nine serotypes
      (1a, 2a, 3a, 1b, 2b, X, Y, 4av and Yv) were identified. Multi-locus sequence
      typing differentiated the isolates into 20 sequence types (STs); 18 were novel.
      Four STs, ST 129, ST 100, ST 126 and ST 18, were most abundant, accounting for
      65% of the isolates. Thirty-nine NotI-pulsed field gel electrophoresis patterns
      (pulsotypes, PTs) were observed; eight PTs were represented by more than one
      isolate with six isolates sharing the PT 13 profile. Multi-locus variable
      nucleotide tandem-repeat analysis recognized 44 different types (MTs); seven MTs
      were represented by more than one isolate and MT 1 was most commonly encountered.
      Correlation between genetic relationships and serotypes was observed among the
      isolates studied; the majority of isolates belonging to the same serotype from
      different years clustered together based on the molecular data. These clustered
      isolates were also from similar geographical origins. These results enhance our
      understanding of genetic relationships between S. flexneri in Guizhou Province
      and can be used to help understand the changing etiology of shigellosis in China.

PMID- 25617840
TI  - Aspergillus oryzae S2 alpha-amylase production under solid state fermentation:
      optimization of culture conditions.
AB  - Aspergillus oryzae S2 was assayed for alpha-amylase production under solid state
      fermentation (SSF). In addition to AmyA and AmyB already produced in monitored
      submerged culture, the strain was noted to produce new AmyB oligomeric forms, in
      particular a dominant tetrameric form named AmyC. The latter was purified to
      homogeneity through fractional acetone precipitation and size exclusion
      chromatography. SDS-PAGE and native PAGE analyses revealed that, purified AmyC
      was an approximately 172 kDa tetramer of four 42 kDa subunits. AmyC was also
      noted to display the same NH2-terminal amino acid sequence residues and
      approximately the same physico-chemical properties of AmyA and AmyB, to exhibit
      maximum activity at pH 5.6 and 60  degrees C, and to produce maltose and
      maltotriose as major starch hydrolysis end-products. Soyabean meal was the best
      substitute to yeast extract compared to fish powder waste and wheat gluten waste.
      AmyC production was optimized under SSF using statistical design methodology.
      Moisture content of 76.25%, C/N substrate ratio of 0.62, and inoculum size of
      10(6.87) spores allowed maximum activity of 22118.34 U/g of dried substrate,
      which was 33 times higher than the one obtained before the application of the
      central composite design (CCD).

PMID- 25617839
TI  - Ewing sarcoma ewsa protein regulates chondrogenesis of Meckel's cartilage through
      modulation of Sox9 in zebrafish.
AB  - Ewing sarcoma is the second most common skeletal (bone and cartilage) cancer in
      adolescents, and it is characterized by the expression of the aberrant chimeric
      fusion gene EWS/FLI1. Wild-type EWS has been proposed to play a role in mitosis,
      splicing and transcription. We have previously shown that EWS/FLI1 interacts with
      EWS, and it inhibits EWS activity in a dominant manner. Ewing sarcoma is a cancer
      that specifically develops in skeletal tissues, and although the above data
      suggests the significance of EWS, its role in chondrogenesis/skeletogenesis is
      not understood. To elucidate the function of EWS in skeletal development, we
      generated and analyzed a maternal zygotic (MZ) ewsa/ewsa line because the ewsa/wt
      and ewsa/ewsa zebrafish appeared to be normal and fertile. Compared with wt/wt,
      the Meckel's cartilage of MZ ewsa/ewsa mutants had a higher number of
      craniofacial prehypertrophic chondrocytes that failed to mature into hypertrophic
      chondrocytes at 4 days post-fertilization (dpf). Ewsa interacted with Sox9, which
      is the master transcription factor for chondrogenesis. Sox9 target genes were
      either upregulated (ctgfa, ctgfb, col2a1a, and col2a1b) or downregulated (sox5,
      nog1, nog2, and bmp4) in MZ ewsa/ewsa embryos compared with the wt/wt zebrafish
      embryos. Among these Sox9 target genes, the chromatin immunoprecipitation (ChIP)
      experiment demonstrated that Ewsa directly binds to ctgfa and ctgfb loci.
      Consistently, immunohistochemistry showed that the Ctgf protein is upregulated in
      the Meckel's cartilage of MZ ewsa/ewsa mutants. Together, we propose that Ewsa
      promotes the differentiation from prehypertrophic chondrocytes to hypertrophic
      chondrocytes of Meckel's cartilage through inhibiting Sox9 binding site of the
      ctgf gene promoter. Because Ewing sarcoma specifically develops in skeletal
      tissue that is originating from chondrocytes, this new role of EWS may provide a
      potential molecular basis of its pathogenesis. 

PMID- 25617841
TI  - Synthesis and in vitro antifungal efficacy of Cu-chitosan nanoparticles against
      pathogenic fungi of tomato.
AB  - Cu-chitosan nanoparticles were synthesized and evaluated for their growth
      promotory and antifungal efficacy in tomato (Solanum lycopersicum Mill). Physico
      chemical characterization of the developed Cu-chitosan nanoparticles was carried
      out by DLS, FTIR, TEM, SEM-EDS and AAS. The study highlighted the stability and
      porous nature of Cu-chitosan nanoparticles. Laboratory synthesized nanoparticles
      showed substantial growth promotory effect on tomato seed germination, seedling
      length, fresh and dry weight at 0.08, 0.10 and 0.12% level. At 0.12%
      concentration these nanoparticles caused 70.5 and 73.5% inhibition of mycelia
      growth and 61.5 and 83.0% inhibition of spore germination in Alternaria solani
      and Fusarium oxysporum, respectively, in an in vitro model. In pot experiments,
      0.12% concentration of Cu-chitosan nanoparticles was found most effective in
      percentage efficacy of disease control (PEDC) in tomato plants with the values of
      87.7% in early blight and 61.1% in Fusarium wilt. The overall results confirm the
      significant growth promotory as well as antifungal capabilities of Cu-chitosan
      nanoparticles. Our model demonstrated the synthesis of Cu-chitosan nanoparticles
      and open up the possibility to use against fungal disease at field level.
      Further, developed porous nanomaterials could be exploited for delivery of
      agrochemicals. 

PMID- 25617842
TI  - Gait variability before surgery and at discharge in patients who undergo total
      knee arthroplasty: a cohort study.
AB  - This study aimed to determine gait ability at hospital discharge in patients
      undergoing total knee arthroplasty (TKA) as an indicator of the risk of falling.
      Fifty-seven patients undergoing primary TKA for knee osteoarthritis participated
      in this study. Gait variability measured with accelerometers and physical
      function including knee range of motion (ROM), quadriceps strength, walking
      speed, and the Timed Up and Go (TUG) test were evaluated preoperatively and at
      discharge from the hospital (1 month before and 5 days after surgery). All
      patients were discharged directly home at 5 days after surgery. Knee flexion of
      ROM, quadriceps strength, walking speed, and the TUG test results were
      significantly worse at hospital discharge than preoperatively (p < 0.001).
      However, gait variability was not significantly different before and after TKA.
      This result indicated that patients following TKA surgery could walk at hospital
      discharge as stably as preoperatively regardless of the decrease in physical
      function, including knee ROM, quadriceps strength, and gait speed after surgery. 

PMID- 25617843
TI  - Prostacyclin receptor expression on platelets of humans with type 2 diabetes is
      inversely correlated with hemoglobin A1c levels.
AB  - Inappropriate platelet aggregation can result in thrombosis and tissue ischemia.
      When compared to healthy human platelets, those of humans with type 2 diabetes
      (DM2) exhibit increased aggregation when stimulated. Activation of the platelet
      prostacyclin receptor (IPR) results in cAMP accumulation and inhibition of
      platelet aggregation. We hypothesized that DM2 platelets express decreased IPR
      when compared to platelets of healthy humans, resulting in decreased IPR agonist
      induced cAMP accumulation. We measured IPR expression with radioligand binding of
      [(3)H]-iloprost, a stable prostacyclin analog, and with Western blotting of the
      IPR protein. Iloprost-stimulated platelet cAMP levels were used to identify the
      functional response to IPR activation. IPR binding, expression of the IPR protein
      and the levels of cAMP in platelets incubated with iloprost were significantly
      decreased in DM2 platelets when compared to platelets of healthy humans. IPR
      expression decreased in platelets as glycemic control of the subjects worsened,
      as indicated by increased hemoglobin A1c levels. Taken together, these findings
      suggest that reduced IPR expression in DM2 platelets may contribute to platelet
      hyperactivity in humans with type 2 diabetes. 

PMID- 25617844
TI  - ADHD and autistic traits, family function, parenting style, and social adjustment
      for Internet addiction among children and adolescents in Taiwan: a longitudinal
      study.
AB  - This longitudinal study investigated the prevalence, predictors, and related
      factors for Internet addiction among elementary and junior high school students
      in Taiwan. A convenient sample of grades 3, 5, and 8 students (n = 1153) was
      recruited from six elementary and one junior high schools. They were assessed
      during the beginning and the end of the spring semester of 2013. Internet
      addiction was examined by the Chen Internet Addiction Scale (CIAS). Other factors
      were screened using the Chinese version of the Autism Spectrum Quotient (AQ) for
      autistic trait, the Parental Bonding Instrument (PBI) for parenting, the Family
      APGAR for family support, the Social Adjustment Inventory for Children and
      Adolescents for social function, and the Swanson, Nolan, and Pelham, version IV
      scale (SNAP-IV) for ADHD symptoms. The prevalence of Internet addiction decreased
      from 11.4% to 10.6%. Male, low family support, poor social adjustment, and high
      ADHD-related symptoms were related to Internet addiction. However, there was an
      inverse relationship between autistic traits and Internet addiction. Further, its
      predictivity could be accounted by poor academic performance, male, and
      protective parenting style. Internet addiction is not uncommon among youths in
      Taiwan. The predictors identified in this study could be the specific measures
      for the development of a prevention program for Internet addiction in the youth
      population.

PMID- 25617845
TI  - Molecular identification of Anisakis and Hysterothylacium larvae in marine fishes
      from the East China Sea and the Pacific coast of central Japan.
AB  - Anisakiasis is a human disease caused by the accidental ingestion of larvae
      belonging to the family Anisakidae. Three fish species, the small yellow croaker
      Pseudosciaena polyactis, the mackerel Pneumatophorus japonicus and the hairtail
      Trichiurus haumela are important source for food products in the East China Sea.
      The prevalence and the identification of Anisakidae larvae in these fishes will
      benefit the prevention and control of anisakiasis. In this study, fish samples
      were obtained from fish markers in the East China Sea and the Pacific coast of
      central Japan during April 2011 and July 2013. For species identification, the
      PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis of the
      entire ITS region (ITS1, 5.8 S and ITS2) of nuclear ribosomal DNA (rDNA) was
      performed. In total, 2004 larvae were collected from 80 hairtail fish, 20 small
      yellow croaker, and 27 mackerel from the East China Sea and the Pacific coast of
      central Japan. High prevalence of Anisakidae larvae infection (116/122, 95.1%)
      was detected in the East China Sea. Seven species were identified belonging to
      the genera Anisakis (Nematoda: Anisakidae) and Hysterothylacium (Nematoda:
      Anisakidae). Anisakis pegreffii was the predominant species accounting for 84.8%
      of all larvae examined in East China Sea, while all Anisakidae larvae isolated
      from Japan were identified as Anisakis simplex sensu stricto (s.s.). In the East
      China Sea, A. simplex s.s. and Anisakis typica were 0.6% (4/619) and 1.5% (9/619)
      of the identified nematodes, respectively. Interestingly, one larva was
      identified as a recombinant genotype of A. simplex s.s. and A. pegreffii. In
      addition, four species of the genus Hysterothylacium, namely, Hysterothylacium
      amoyense (31/619, 5.0%), Hysterothylacium aduncum (10/619, 1.6%),
      Hysterothylacium fabri (21/619, 3.4%) and Hysterothylacium spp. (18/619, 2.9%)
      were also identified in the present study. This is a comprehensive
      epidemiological dataset for the family Anisakidae in the East China Sea. The
      identification of A. typica, recombinant genotype of A. simplex s.s. and A.
      pegreffii, H. amoyense and H. fabri is first reported in this area. The wide
      diversity and substantial geographical distributions of these nematodes will
      provide a foundation for future studies of Anisakidae family. The high prevalence
      of these nematodes in marine fishes off the East China Sea may pose considerable
      food safety problems, which is a potential cause of human anisakiasis. 

PMID- 25617846
TI  - Two-dimensional infrared spectroscopic study on the thermally induced structural
      changes of glutaraldehyde-crosslinked collagen.
AB  - The thermal stability of collagen solution (5 mg/mL) crosslinked by
      glutaraldehyde (GTA) [GTA/collagen (w/w)=0.5] was measured by differential
      scanning calorimetry and Fourier transform infrared spectroscopy (FTIR), and the
      thermally induced structural changes were analyzed using two-dimensional (2D)
      correlation spectra. The denaturation temperature (Td) and enthalpy change
      (DeltaH) of crosslinked collagen were respectively about 27 degrees C and 88 J/g
      higher than those of native collagen, illuminating the thermal stability
      increased. With the increase of temperature, the red-shift of absorption bands
      and the decreased AIII/A1455 value obtained from FTIR spectra indicated that
      hydrogen bonds were weakened and the unwinding of triple helix occurred for both
      native and crosslinked collagens; whereas the less changes in red-shifting and
      AIII/A1455 values for crosslinked collagen also confirmed the increase in thermal
      stability. Additionally, the 2D correlation analysis provided information about
      the thermally induced structural changes. In the 2D synchronous spectra, the
      intensities of auto-peaks at 1655 and 1555 cm(-1), respectively assigned to amide
      I band (CO stretching vibration) and amide II band (combination of NH bending and
      CN stretching vibrations) in helical conformation were weaker for crosslinked
      collagen than those for native collagen, indicating that the helical structure of
      crosslinked collagen was less sensitive to temperature. Moreover, the sequence of
      the band intensity variations showed that the band at 1555 cm(-1) moved backwards
      owing to the addition of GTA, demonstrating that the response of helical
      structure of crosslinked collagen to the increased temperature lagged. It was
      speculated that the stabilization of collagen by GTA was due to the reinforcement
      of triple helical structure.

PMID- 25617847
TI  - Optical and spectral studies on pure and europium doped olgite type Na(Sr,Ba)PO4
      ceramics.
AB  - Europium ion doped olgite type Na(Sr,Ba)PO4 ceramics, a new generation of light
      emitting bulb, was prepared by a high temperature solid-state reaction method.
      The synthesized materials were subjected to various characterizations such as X
      ray powder diffraction, Scanning electron microscopy and FT-IR spectra
      measurements. The EPR spectrum of the sample exhibits a well-resolved hyperfine
      structure of 151Eu2+ and 153Eu2+ isotopes and the g value has been calculated.
      Fluorescence spectra revealed that europium ions were present in divalent as well
      as in the trivalent oxidation states. The critical distance for energy transfer
      between Eu2+ and Eu2+ ion is calculated as 20A, which is in good agreement with
      that of experimental data. The FTIR analysis reveals all the vibrations of PO4(3
      ) ions.

PMID- 25617848
TI  - Spectroscopic studies on interaction of BSA and Eu(III) complexes with H5ph-dtpa
      and H5dtpa ligands.
AB  - An novel aromatic aminopolycarboxylic acid ligand, N-(2-N,N
      Dicarboxymethylaminophenyl) ethylenediamine-N,N',N'-triacetic acid (H5ph-dtpa),
      was synthesized by improving experimental method and its corresponding Eu(III)
      complex, Na2[EuIII(ph-dtpa)(H2O)].6H2O, was successfully prepared through heat
      refluxing method. As a comparison, the Eu(III) complex with diethylenetriamine
      N,N,N',N',N"-pentaacetic acid (H5dtpa) ligand, Na2[Eu(III)(dtpa)(H2O)].6H2O, was
      also prepared by the same method. And then, the interaction between prepared
      Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) and bovine
      serum albumin (BSA) in aqueous solution were studied by the combination of
      ultraviolet-visible (UV-vis), fluorescence and circular dichroism (CD)
      spectroscopies. In addition, the binding sites of Eu(III) complexes
      ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) to BSA molecules were also
      estimated by synchronous fluorescence. Moreover, the theoretical and experimental
      results show that the Van der Waals, hydrogen bond and pi-pi stacking
      interactions are the mainly impulse to the reaction. The binding distances (r)
      between Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) and
      BSA were obtained according to Forster's non-radiative energy transfer theory.
      Also, the determined UV-vis absorption spectroscopy, synchronous fluorescence and
      circular dichroism (CD) spectra showed that the conformation of BSA could be
      changed in the presence of Eu(III) complexes. The obtained results can help
      understand the action mode between rare earth metal complexes of
      aminopolycarboxylic acid ligands with BSA and they are also expected to provide
      important information of designs of new inspired drugs.

PMID- 25617849
TI  - Theoretical design of triphenylamine-based derivatives with asymmetric D-D-pi-A
      configuration for dye-sensitized solar cells.
AB  - The use of theoretical techniques in the structural development of dye-sensitized
      solar cells helps in the efficient screening of the dyes. To properly rationalize
      the dye's design process, benchmark calculations were conducted using long-range
      corrected exchange-correlation (xc) functionals with varying separation
      parameters to be able to predict the excited-state energies of triphenylamine
      based dyes, namely: PPS, PSP, and PSS, wherein they differ at the pi-conjugated
      bridge using thiophene and/or phenyl moieties. The results show that LC-omegaPBE
      xc functional with an optimized parameter provided better correlation with the
      experimental results compared to the other functionals. The relative shifts of
      the absorption spectra, light harvesting efficiency, normal dipole moments, as
      well as the ionization potentials and electron affinities of the dyes were well
      correlated with the experimental data. A new set of dyes was designed in an
      effort to increase its solar cell efficiency that was patterned after PSS with an
      additional donor moiety such as fluorene, cyclopentaindole, and pyrene attached
      asymmetrically at the triphenylamine ring. Among the newly designed dyes, analogs
      that contain 4-phenyl-1,2,3,4-tetrahydrocyclopenta[b]indole (I) and pyrido[2,3,4
      5-imn]phenanthridine-5,10(4H,9H)-dione (P2) as the additional donor moiety
      produced the best photophysical properties and charge-transfer characteristics
      for a promising dye for solar cell applications. 

PMID- 25617850
TI  - Impact of action planning on spatial perception: attention matters.
AB  - Previous research suggested that perception of spatial location is biased towards
      spatial goals of planned hand movements. In the present study I show that an
      analogous perceptual distortion can be observed if attention is paid to a spatial
      location in the absence of planning a hand movement. Participants judged the
      position of a target during preparation of a mouse movement, the end point of
      which could deviate from the target by a varying degree in Exp. 1. Judgments of
      target position were systematically affected by movement characteristics
      consistent with perceptual assimilation between the target and the planned
      movement goal. This effect was neither due to an impact of motor execution on
      judgments (Exp. 2) nor due to characteristics of the movement cues or of certain
      target positions (Exp. 3, Exp. 5A). When the task included deployment of
      attention to spatial positions (former movement goals) in preparation for a
      secondary perceptual task, an effect emerged that was comparable with the bias
      associated with movement planning (Exp. 4, Exp. 5B). These results indicate that
      visual distortions accompanying manipulations of variables related to action
      could be mediated by attentional mechanisms. 

PMID- 25617852
TI  - Environmental control on fish and macrocrustacean spring community-structure, on
      an intertidal sandy beach.
AB  - The inter-annual variability of the fish and macrocrustacean spring community on
      an intertidal sandy beach near the Canche estuary (North of France) was studied
      from 2000 to 2013 based on weekly spring sampling over an 11-year period. Twenty
      eight species representing 21 families were collected during the course of the
      study. The community was dominated by a few abundant species accounting for > 99%
      of the total species densities. Most individuals caught were young-of-the-year
      indicating the importance of this ecosystem for juvenile fishes and
      macrocrustaceans. Although standard qualitative community ecology metrics
      (species composition, richness, diversity, evenness and similarity) indicated
      notable stability over the study period, community structure showed a clear
      change since 2009. Densities of P. platessa, P. microps and A. tobianus decreased
      significantly since 2009, whereas over the period 2010-2013, the contribution of
      S. sprattus to total species density increased 4-fold. Co-inertia and generalised
      linear model analyses identified winter NAO index, water temperature, salinity
      and suspended particular matter as the major environmental factors explaining
      these changes. Although the recurrent and dense spring blooms of the
      Prymnesiophyte Phaeocystis globosa is one of the main potential threats in
      shallow waters of the eastern English Channel, no negative impact of its temporal
      change was detected on the fish and macrocrustacean spring community structure. 

PMID- 25617851
TI  - The effects of pleiotrophin in proliferative diabetic retinopathy.
AB  - Pleiotrophin (PTN), a secreted, multifunctional cytokine, is involved in
      angiogenic, fibrotic and neurodegenerative diseases. However, little is known
      about its effects on diabetic retinopathy, a neurovascular disease. To
      investigate the role of PTN in proliferative diabetic retinopathy (PDR), PTN
      concentration in the vitreous was evaluated in PDR patients and non-diabetic
      controls. PTN expression was observed in epiretinal membranes from patients. PTN
      knockdown was performed using small interfering (si)RNA, and the effects on
      retinal pigment epithelium (RPE) cells and human umbilical vascular endothelia
      cells (HUVECs) were observed in vitro under hyperglycemic and hypoxic conditions.
      Cell attachment, proliferation, migration, tube formation, cell cycle, apoptosis,
      extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, and VEGF
      levels were studied. The vitreous PTN concentration in PDR patients was higher
      than that in non-diabetic controls, and PTN was highly expressed in the
      fibrovascular membranes of PDR patients. Under hyperglycemic and hypoxic
      conditions, PTN knockdown reduced cell attachment, proliferation, migration, and
      tube formation and induced cell cycle arrest and apoptosis in vitro.
      Mechanically, PTN depletion decreased ERK 1/2 phosphorylation. Recombinant PTN up
      regulated the concentration of VEGF in vitro, which can be attenuated by the ERK
      1/2 inhibitor. Taken together, our results implied that elevated PTN in PDR
      patients might participate in the critical processes of the development of PDR,
      most likely playing roles in angiogenesis and proliferation, possibly by
      activating the ERK 1/2 pathway and regulating VEGF secretion. These findings
      provide new insight into the roles of PTN in PDR and suggest that PTN may become
      a new target for therapeutic intervention in PDR. 

PMID- 25617853
TI  - The preliminary study of 16alpha-[18F]fluoroestradiol PET/CT in assisting the
      individualized treatment decisions of breast cancer patients.
AB  - OBJECTIVE: To evaluate the clinical value of 16alpha-[18F]fluoroestradiol (18F
      FES) PET/CT in assisting the individualized treatment decisions of breast cancer
      patients. METHODS: Thirty-three breast cancer patients, who underwent both 18F
      FES and 18F-FDG PET/CT from July 2010 to March 2013 in our center, were enrolled
      in this preliminary study. All the patients used 18F-FES PET/CT as a diagnostic
      tool with a clinical dilemma. We used the maximum Standardized Uptake Value
      (SUVmax) to quantify ER expression and a cutoff value of 1.5 to dichotomize
      results into ER positive and negative lesions. All patients were clinically
      followed up at least 6 months. RESULTS: In evaluating equivocal lesions on
      conventional work-up group (n = 4), three lung lesions and another iliac lesion
      were enrolled. As for three lung lesions, 18F-FES PET/CT showed one lesion with
      high uptake, which suggested it was an ER positive metastasis. The other two
      lesions were 18F-FES negative, which meant an ER negative metastasis or secondary
      primary tumor. Additionally, one iliac lesion was detected by MRI. 18F-FDG uptake
      was high at the suspected lesion, whereas 18F-FES uptake was absent; In
      predicting origin of metastasis group (n = 2), two breast cancer patients had
      secondary primary tumors were collected. They were 18F-FES negative, which showed
      low possibility of metastasis from breast cancer and they were all confirmed by
      biopsy. In detecting ER status in metastasis group (n = 27), 18F-FES PET/CT
      showed increased 18F-FES uptake in all metastatic lesions in 11 patients; absent
      in all lesions in 13 patients; and the remaining 3 patients had both 18F-FES
      positive and negative lesions. Totally, on the basis of the 18F-FES PET/CT
      results, we found changes in the treatment plans in 16 patients (48.5%, 16/33).
      CONCLUSIONS: 18F-FES PET/CT could assess the entire tumor volume receptor status;
      therefore, it may be used to assist the individualized treatment decisions of
      breast cancer patients.

PMID- 25617854
TI  - Microplastics are taken up by mussels (Mytilus edulis) and lugworms (Arenicola
      marina) living in natural habitats.
AB  - We studied the uptake of microplastics under field conditions. At six locations
      along the French-Belgian-Dutch coastline we collected two species of marine
      invertebrates representing different feeding strategies: the blue mussel Mytilus
      edulis (filter feeder) and the lugworm Arenicola marina (deposit feeder).
      Additional laboratory experiments were performed to assess possible (adverse)
      effects of ingestion and translocation of microplastics on the energy metabolism
      (cellular energy allocation) of these species. Microplastics were present in all
      organisms collected in the field: on average 0.2 +/- 0.3 microplastics g(-1) (M.
      edulis) and 1.2 +/- 2.8 particles g(-1) (A. marina). In a proof of principle
      laboratory experiment, mussels and lugworms exposed to high concentrations of
      polystyrene microspheres (110 particles mL(-1) seawater and 110 particles g(-1)
      sediment, respectively) showed no significant adverse effect on the organisms'
      overall energy budget. The results are discussed in the context of possible risks
      as a result of the possible transfer of adsorbed contaminants.

PMID- 25617855
TI  - Levels and source apportionment of children's lead exposure: could urinary lead
      be used to identify the levels and sources of children's lead pollution?
AB  - As a highly toxic heavy metal, the pollution and exposure risks of lead are of
      widespread concern for human health. However, the collection of blood samples for
      use as an indicator of lead pollution is not always feasible in most cohort or
      longitudinal studies, especially those involving children health. To evaluate the
      potential use of urinary lead as an indicator of exposure levels and source
      apportionment, accompanying with environmental media samples, lead concentrations
      and isotopic measurements (expressed as (207)Pb/(206)Pb, (208)Pb/(206)Pb and
      (204)Pb/(206)Pb) were investigated and compared between blood and urine from
      children living in the vicinities of a typical coking plant and lead-acid battery
      factory. The results showed urinary lead might not be a preferable proxy for
      estimating blood lead levels. Fortunately, urinary lead isotopic measurements
      could be used as an alternative for identifying the sources of children's lead
      exposure, which coincided well with the blood lead isotope ratio analysis. 

PMID- 25617856
TI  - High serum uric acid is associated with increased cardio-ankle vascular index
      (CAVI) in healthy Japanese subjects: a cross-sectional study.
AB  - OBJECTIVE: To investigate the association of serum uric acid (SUA) with arterial
      stiffness assessed by cardio-ankle vascular index (CAVI). METHODS: We analyzed
      the cross-sectional data from 27,360 healthy Japanese subjects (12,910 males and
      14,450 females) aged between 20 and 74 years without a past history of heart
      disease, stroke, hypertension, diabetes, nephritis or gout. We investigated
      whether SUA was independently associated with CAVI in a gender-specific manner.
      RESULTS: BMI, CAVI, systolic/diastolic BP, GOT, GPT, gamma-GTP, triglyceride
      (TG), creatinine and SUA were higher and HDL-C was lower in males than in
      females. Next, they were stratified by SUA into 3 groups: lower tertile (T1),
      middle tertile (T2) and upper tertile (T3) and by gender. CAVI increased
      progressive with increasing SUA tertile, after adjusting for age, BMI and
      systolic BP (sBP) identified in multiple regression analysis for CAVI.
      Multivariate analysis showed that the odds ratios (95% CI) relative to T1 for
      high CAVI (>=90(th) percentile) were 1.233 (0.928-1.638) in T2 and 1.352 (1.031
      1.773) in T3 for males, and 1.133 (0.984-1.303) in T2 and 1.361 (1.098-1.687) in
      T3 for females, after adjusting for confounders. Furthermore, increase in
      adjusted CAVI was observed in a lower SUA range in females compared to that
      observed in males. CONCLUSION: We demonstrated an independent correlation between
      SUA and CAVI, and observed gender difference in the SUA range for increase in
      CAVI. These results may suggest the need to set different target SUA levels for
      men and women in anti-hyperuricemic treatment for atherosclerosis prevention.

PMID- 25617857
TI  - Carotid extra-media thickness in obesity and metabolic syndrome: a novel index of
      perivascular adipose tissue: extra-media thickness in obesity and metabolic
      syndrome.
AB  - OBJECTIVES: We aimed to evaluate the association between a novel ultrasound index
      extra-media thickness (EMT), obesity, and metabolic syndrome (MS) using several
      measures of adiposity. METHODS: Four hundred patients were included in the study
      (age: 60.95 +/- 7.3 years, F/M: 35/65%). Both common carotid arteries (CCA)
      indexes (EMT and intima-media thickness), anthropometric parameters, body fat
      percentage and ultrasound measures of different fat depots were obtained in all
      patients. MS was identified using three alternative definitions: International
      Diabetes Federation 2005 (IDF), National Cholesterol Education Program Adult
      Treatment Panel III 2001 (NCEP ATP III) and World Health Organization 1998 (WHO).
      RESULTS: The study group included patients with very high (80.2%) or high (19.8%)
      CV risk (IDF MS: 59.5%). Carotid EMT measures averaged from both sides (+/-SD)
      were as follows: mean EMT: 791 +/- 126 MUm, mean minimum EMT: 731 +/- 115 MUm and
      mean maximum EMT: 885 +/- 210 MUm. Patients with MS, irrespective of its
      definition and measures of obesity, displayed significantly thicker mean EMT
      compared to non-MS individuals: 819 +/- 129 MUm vs 747 +/- 113 MUm (p < 0.001;
      IDF), 824 +/- 131 MUm vs 751 +/- 112 MUm (p < 0.001; NCEP ATP III) and 825 +/-
      137 MUm vs 773 +/- 120 MUm (p < 0.001; WHO). Moreover, EMT was related to all
      major parameters of general obesity, abdominal fat distribution, regional neck
      subcutaneous fat with weaker association between EMT and epicardial fat
      thickness. Finally, EMT is associated with an increasing number of CV risk
      factors. CONCLUSIONS: This is the first study providing novel findings on the
      relationship between EMT, MS, and adiposity indexes. Our results suggest that EMT
      may be a new non-invasive index of perivascular adipose tissue corresponding to
      cardiometabolic risk.

PMID- 25617858
TI  - Palmolein and olive oil consumed within a high protein test meal have similar
      effects on postprandial endothelial function in overweight and obese men: A
      randomized controlled trial.
AB  - OBJECTIVE: This study assessed the postprandial effects of high fat, high protein
      meals containing either palmolein or olive oil on endothelial function in
      overweight/obese men. DESIGN: 28 men (32-65 yr; 25-35 kg/m(2)) consumed, in
      random order 1 wk apart, isocaloric high protein, high fat meals (2791 kJ, 40 g
      protein (~3 g l-arginine), 44 g fat, 21 g carbohydrate) prepared with either 40 g
      palmolein or 40 g olive oil after an overnight fast. The SFA:MUFA:PUFA ratio of
      the oils were: palmolein, 42:47:12; olive oil, 17:76:7. Brachial artery flow
      mediated dilatation (FMD), circulating endothelial function markers,
      nitrotyrosine (oxidative stress marker), triglycerides, glucose and insulin were
      assessed pre-meal and hourly for 5 h. Mixed model procedures were used to analyze
      the data. RESULTS: Meal consumption increased serum triglycerides (time effect, P
      < 0.001); with no meal differences (meal * time interaction, P = 0.93). Serum
      insulin peaked 1 h post-consumption and returned to pre-meal concentrations by 5
      h with both meals (time effect, P < 0.001; meal * time effect, P = 0.68). FMD,
      serum intercellular adhesion molecule-1 (ICAM-1) and E-selectin did not change
      (meal * time effect, P > 0.4). Olive oil transiently increased plasma
      nitrotyrosine after 1 h compared to palmolein (meal * time interaction, P =
      0.002) whereas both meals increased serum vascular cell adhesion molecule-1 (VCAM
      1) after 1 h (time effect, P < 0.001; meal * time interaction, P = 0.98). Both
      nitrotyrosine and VCAM-1 returned to pre-meal concentrations after 2 h.
      CONCLUSION: In the context of a high protein meal, palmolein similarly to olive
      oil did not affect postprandial endothelial function in overweight/obese men.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR)
      (http://www.anzctr.org.au/default.aspx). Trial ID: ACTRN12613000136707.

PMID- 25617859
TI  - Plasma endothelin-1 and cardiovascular risk among young and healthy adults.
AB  - OBJECTIVES: Endothelial dysfunction is a major precursor of atherosclerosis. The
      aim of this study was to assess the interrelationships between plasma endothelin
      1 (ET-1) levels and cardiovascular risk among young and healthy individuals.
      METHODS: We performed a population-based study among 2160 healthy adults aged
      between 25 and 41 years in the Principality of Liechtenstein. Individuals with
      prevalent cardiovascular disease, diabetes or a body mass index >35 kg/m(2) were
      excluded. Plasma ET-1 was measured using a novel high-sensitive, single-molecule
      counting technology. The relationships between plasma levels of ET-1 and various
      cardiovascular risk factors were assessed by multivariable regression analyses.
      RESULTS: Median age of our population was 37 years. Median ET-1 levels across ET
      1 quartiles were 1.86, 2.33, 2.76 and 3.48 pg/mL. After multivariable adjustment,
      there were significant correlations of ET-1 with systolic blood pressure (beta
      per 1-unit increase in log transformed ET-1 2.30 (95% confidence interval (CI)
      1.03; 3.58, p = 0.0004), C-reactive protein (beta 0.19 (95% CI 0.03; 0.34, p =
      0.021), glomerular filtration rate (beta -1.73 (95% CI -3.17; -0.29, p = 0.019),
      and current smoking (Odds ratio 1.94 (95% CI 1.39; 2.71, p < 0.0001). We also
      found a highly significant association between ET-1 levels and overall
      cardiovascular risk estimated by the "Prospective Cardiovascular Munster"
      (PROCAM) and the Framingham score (beta 0.18 (95% CI 0.06; 0.31, p = 0.004, and
      beta 0.11 (95% CI 0.05; 0.16), p < 0.0001, respectively). CONCLUSIONS: Plasma ET
      1 levels are easily measurable in healthy adults and correlate with major
      cardiovascular risk factors and global cardiovascular risk.

PMID- 25617860
TI  - A concise review of non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the
      metabolic syndrome and the incidence of which is rising rapidly due to the
      increasing epidemic of obesity in both adults and children. The initial
      accumulation of fat followed by subsequent inflammation is central to the
      development of liver damage, and is critically influenced by host factors
      including age, gender, presence of diabetes, genetic polymorphisms and more
      recently by the gut microbiome. An increasing body of data suggest that NAFLD is
      also an independent risk factor of cardiovascular disease, which remains the
      commonest cause of mortality in such patients. This review focusses on the
      pathogenesis of NAFLD, and the evolution of new approaches to the management and
      treatment of NAFLD. 

PMID- 25617861
TI  - Cue generation and memory construction in direct and generative autobiographical
      memory retrieval.
AB  - Theories of autobiographical memory emphasise effortful, generative search
      processes in memory retrieval. However recent research suggests that memories are
      often retrieved directly, without effortful search. We investigated whether
      direct and generative retrieval differed in the characteristics of memories
      recalled, or only in terms of retrieval latency. Participants recalled
      autobiographical memories in response to cue words. For each memory, they
      reported whether it was retrieved directly or generatively, rated its visuo
      spatial perspective, and judged its accompanying recollective experience. Our
      results indicated that direct retrieval was commonly reported and was faster than
      generative retrieval, replicating recent findings. The characteristics of
      directly retrieved memories differed from generatively retrieved memories:
      directly retrieved memories had higher field perspective ratings and lower
      observer perspective ratings. However, retrieval mode did not influence
      recollective experience. We discuss our findings in terms of cue generation and
      content construction, and the implication for reconstructive models of
      autobiographical memory. 

PMID- 25617862
TI  - Serial assessment of right ventricular function using tissue Doppler imaging in
      preterm infants within 7 days of life.
AB  - BACKGROUND: We aimed to evaluate right ventricular (RV) function longitudinally
      using tissue Doppler imaging (TDI) echocardiography in preterm infants. METHODS:
      We selected 101 very-low-birth-weight (VLBW) infants for the study.
      Echocardiographic examinations including TDI were performed serially within 7days
      of life. Pulsed-Doppler TDI waveforms were recorded at the tricuspid valve
      annulus, and peak systolic velocities (Sa), early diastolic velocities (Ea), and
      late diastolic velocities (Aa) were measured. RESULTS: Sa, Ea and Aa were all
      reduced significantly from 3h to 12h, and then increased gradually thereafter.
      These three velocities also increased with gestational age in the early neonatal
      period. The ratio of Ea to Aa (Ea/Aa) did not change significantly within the
      first week of life. The ratio of E to Ea (E/Ea) in VLBW infants also seemed to
      remain stable from birth to day 7. The values of Sa appeared to be associated
      with cardiac output in the early neonatal period. Both Sa and Aa in intubated
      infants were significantly higher than in non-intubated infants. CONCLUSION: RV
      TDI velocities of preterm infants in the early neonatal period are influenced by
      gestational age, postnatal age, and respiratory status, although the RV E/Ea
      ratio appears to be almost stable throughout the neonatal period. Our findings
      may provide some basis for assessment of RV function in critically ill preterm
      infants.

PMID- 25617863
TI  - Attention problems in relation to gestational age at birth and smallness for
      gestational age.
AB  - BACKGROUND: While it is well established that very preterm birth (gestational age
      at birth <32 weeks) is related to increased attention problems, there is still
      considerable uncertainty of the effects of moderate or late preterm birth or
      smallness for gestational age (SGA) on attention regulation. AIMS: To investigate
      the impact of gestational age at birth and SGA, birth on child attention
      problems. STUDY DESIGN: Prospective longitudinal cohort study. SUBJECTS: A total
      of 1435 children sampled from the Bavarian Longitudinal Study (BLS). OUTCOME
      MEASURES: Main outcome variables were parent-reported attention problems and
      examiner-reported attention skills at 6 and 8 years. Predictors were linked to
      attention outcomes using hierarchical regression analyses. RESULTS: Gestational
      age at birth ranged from 25 weeks to 41 weeks. We found a quadratic effect of
      gestational age on attention problems (beta6 years=0.161, 95% CI=0.085; 0.236;
      beta8 years=0.211, 95% CI=0.135; 0.287), and attention skills at 6 and 8 years
      (beta6 years=-0.178, 95% CI=-0.252; -0.104; beta8 years=-0.169, 95% CI=-0.243; 
      0.094). Elective caesarean birth did not predict child attention. In adjusted
      models, SGA was an additional risk factor for attention problems (beta=0.080, 95%
      CI=0.026; 0.134), and attention skills (beta=-0.091, 95% CI=-0.143; -0.039) at 6
      years but not at 8 years after adjusting for child sex and family SES.
      CONCLUSION: Adverse effects on attention are disproportionately higher at early
      gestations. In contrast, the impact of SGA status was found to be similar at all
      gestational ages but disappeared by 8 years.

PMID- 25617864
TI  - The neuropathology of stillbirth - correlation with apolipoprotein genotype in a
      Scottish population based study.
AB  - BACKGROUND: The neuropathology of stillbirths has been widely studied but rarely
      on a population basis. Whether foetal apolipoprotein E (APOE) genotype exerts any
      influence has been little investigated, despite well known effects in adult
      brains. AIMS: To establish the neuropathology of a population cohort of
      stillbirths and compare with the APOE genotype. STUDY DESIGN AND SUBJECTS: The
      brains of 191 stillbirths (>=24weeks of gestation) were recruited from a Scottish
      population cohort and grouped by clinical history. APOE genotype was available
      for 97%. RESULTS AND CONCLUSIONS: One or more neuropathological features, most
      appearing relatively recent, were found in 54% of 157 antepartum singletons, 44%
      of 9 abruption-associated stillbirths, 85% of 13 in multiple pregnancies but in
      only 19% of 12 intrapartum stillbirths. White matter injury (WMI) occurred in 36%
      of preterm and 21% mature stillbirths. Fresh petechial haemorrhages were common
      in all groups (29%) but germinal matrix haemorrhage (GMH) (7%) and
      periventricular leucomalacia (1%) were confined to preterm. GMH was significantly
      associated with WMI (p=0.003). Placental inflammation was common in intrapartum
      stillbirths (50%), compared with antepartum (15%), multiple pregnancy (23%) and
      abruption (0%). beta-Amyloid precursor protein (betaAPP) positive axons (36%
      stillbirths overall) correlated closely with WMI (p<0.0001), justifying future
      routine inclusion in foetal neuropathological investigation. This study
      highlights the paucity of brain damage in intrapartum stillbirths. While APOE2
      was significantly overrepresented in stillbirths, there was no correlation
      between APOE genotype and neuropathological findings. We conclude that APOE does
      not influence neuropathological outcomes in stillbirths.

PMID- 25617865
TI  - Identification of valid reference genes for the normalization of RT-qPCR
      expression studies in human breast cancer cell lines treated with and without
      transient transfection.
AB  - Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a
      powerful technique for examining gene expression changes during tumorigenesis.
      Target gene expression is generally normalized by a stably expressed endogenous
      reference gene; however, reference gene expression may differ among tissues under
      various circumstances. Because no valid reference genes have been documented for
      human breast cancer cell lines containing different cancer subtypes treated with
      transient transfection, we identified appropriate and reliable reference genes
      from thirteen candidates in a panel of 10 normal and cancerous human breast cell
      lines under experimental conditions with/without transfection treatments with two
      transfection reagents. Reference gene expression stability was calculated using
      four algorithms (geNorm, NormFinder, BestKeeper and comparative delta Ct), and
      the recommended comprehensive ranking was provided using geometric means of the
      ranking values using the RefFinder tool. GeNorm analysis revealed that two
      reference genes should be sufficient for all cases in this study. A stability
      analysis suggests that 18S rRNA-ACTB is the best reference gene combination
      across all cell lines; ACTB-GAPDH is best for basal breast cancer cell lines; and
      HSPCB-ACTB is best for ER+ breast cancer cells. After transfection, the stability
      ranking of the reference gene fluctuated, especially with Lipofectamine 2000
      transfection reagent in two subtypes of basal and ER+ breast cell lines.
      Comparisons of relative target gene (HER2) expression revealed different
      expressional patterns depending on the reference genes used for normalization. We
      suggest that identifying the most stable and suitable reference genes is critical
      for studying specific cell lines under certain circumstances. 

PMID- 25617866
TI  - Degradation of chlorpyrifos in tropical rice soils.
AB  - Chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinol) phosphorothioate] is
      used worldwide as an agricultural insecticide against a broad spectrum of insect
      pests of economically important crops including rice, and soil application to
      control termites. The insecticide mostly undergoes hydrolysis to diethyl
      thiophosphoric acid (DETP) and 3,5,6-trichloro-2-pyridinol (TCP), and negligible
      amounts of other intermediate products. In a laboratory-cum-greenhouse study,
      chlorpyrifos, applied at a rate of 10 mg kg(-1) soil to five tropical rice soils
      of wide physico-chemical variability, degraded with a half-life ranging from
      27.07 to 3.82 days. TCP was the major metabolite under both non-flooded and
      flooded conditions. Chlorpyrifos degradation had significant negative
      relationship with electrical conductivity (EC), cation exchange capacity (CEC),
      clay and sand contents of the soils under non-flooded conditions. Results
      indicate that degradation of chlorpyrifos was accelerated with increase in its
      application frequency, across the representative rice soils. Management regimes
      including moisture content and presence or absence of rice plants also influenced
      the process. Biotic factors also play an important role in the degradation of
      chlorpyrifos as demonstrated by its convincing degradation in mineral salts
      medium inoculated with non-sterile soil suspension. 

PMID- 25617867
TI  - Dark fermentation of complex waste biomass for biohydrogen production by
      pretreated thermophilic anaerobic digestate.
AB  - The Biohydrogen Potential (BHP) of six different types of waste biomass typical
      for the Campania Region (Italy) was investigated. Anaerobic sludge pre-treated
      with the specific methanogenic inhibitor sodium 2-bromoethanesulfonic acid (BESA)
      was used as seed inoculum. The BESA pre-treatment yielded the highest BHP in BHP
      tests carried out with pre-treated anaerobic sludge using potato and pumpkin
      waste as the substrates, in comparison with aeration or heat shock pre-treatment.
      The BHP tests carried out with different complex waste biomass showed average BHP
      values in a decreasing order from potato and pumpkin wastes (171.1 +/- 7.3 ml
      H2/g VS) to buffalo manure (135.6 +/- 4.1 ml H2/g VS), dried blood (slaughter
      house waste, 87.6 +/- 4.1 ml H2/g VS), fennel waste (58.1 +/- 29.8 ml H2/g VS),
      olive pomace (54.9 +/- 5.4 ml H2/g VS) and olive mill wastewater (46.0 +/- 15.6
      ml H2/g VS). The digestate was analyzed for major soluble metabolites to
      elucidate the different biochemical pathways in the BHP tests. These showed the
      H2 was produced via mixed type fermentation pathways. 

PMID- 25617868
TI  - Granular activated carbon for simultaneous adsorption and biodegradation of toxic
      oil sands process-affected water organic compounds.
AB  - Naphthenic acids (NAs) released into oil sands process-affected water (OSPW)
      during bitumen processing in Northern Alberta are problematic for oil sands
      industries due to their toxicity in the environment and resistance to degradation
      during conventional wastewater treatment processes. Granular activated carbon
      (GAC) has shown to be an effective media in removing biopersistent organics from
      wastewater using a combination of adsorption and biodegradation removal
      mechanisms. A simultaneous GAC (0.4 g GAC/L) adsorption and biodegradation
      (combined treatment) study was used for the treatment of raw and ozonated OSPW.
      After 28 days of batch treatment, classical and oxidized NAs removals for raw
      OSPW were 93.3% and 73.7%, and for ozonated OSPW were 96.2% and 77.1%,
      respectively. Synergetic effects of the combined treatment process were observed
      in removals of COD, the acid extractable fraction, and oxidized NAs, which
      indicated enhanced biodegradation and bioregeneration in GAC biofilms. A bacteria
      copy number >10(8) copies/g GAC on GAC surfaces was found using quantitative real
      time polymerase chain reaction after treatment for both raw and ozonated OSPW. A
      Microtox((r)) acute toxicity test (Vibrio fischeri) showed effective toxicity
      removal (>95.3%) for the combined treatments. Therefore, the simultaneous GAC
      adsorption and biodegradation treatment process is a promising technology for the
      elimination of toxic OSPW NAs. 

PMID- 25617869
TI  - A novel "wastes-treat-wastes" technology: role and potential of spent fluid
      catalytic cracking catalyst assisted ozonation of petrochemical wastewater.
AB  - Catalytic ozonation is a promising wastewater treatment technology. However, the
      high cost of the catalyst hinders its application. A novel "wastes-treat-wastes"
      technology was developed to reuse spent fluid catalytic cracking catalysts
      (sFCCc) for the ozonation of petrochemical wastewater in this study. Multivalent
      vanadium (V(4+) and V(5+)), iron (Fe(2+) and Fe(3+)) and nickel (Ni(2+)) oxides
      that are distributed on the surface of sFCCc and poisoned FCC catalysts are the
      catalytic components for ozonation. The sFCCc assisted catalytic ozonation (sFCCc
      O) of nitrobenzene indicated that the sFCCc significantly promoted hydroxyl
      radical mediated oxidation. The degradation rate constant of nitrobenzene in
      sFCCc-O (0.0794 min(-1) at 298 K) was approximately doubled in comparison with
      that in single ozonation (0.0362 min(-1) at 298 K). The sFCCc-O of petrochemical
      wastewater increased chemical oxygen demand removal efficiency by three-fold
      relative to single ozonation. The number of oxygen-containing (Ox) polar
      contaminants in the effluent (253) from sFCCc-O treatment decreased to about 70%
      of the initial wastewater (353). The increased oxygen/carbon atomic ratio and
      decreased number of Ox polar contaminants indicated a high degree of degradation.
      The present study showed the role and potential of sFCCc for catalytic ozonation
      of petrochemical wastewater, particularly in an advantage of the cost
      effectiveness through "wastes-treat-wastes". 

PMID- 25617870
TI  - The use of superporous p(3-acrylamidopropyl)trimethyl ammonium chloride cryogels
      for removal of toxic arsenate anions.
AB  - Poly((3-Acrylamidopropyl)trimethylammonium chloride) (p(APTMACl)) cryogels were
      used as a superporous polymer network for the removal of toxic arsenate anions
      from an aqueous medium. The fast swelling in water, in about 7 s, was shown to be
      very useful leading to fast arsenate adsorption by p(APTMACl) cryogels within 30
      min in comparison to 12 h for bulk common p(APTMACl) hydrogels. A maximum
      adsorption capacity of about 120 (mg/g) arsenate was obtained for p(APTMACl)
      cryogels. Both the Langmuir and Freundlich adsorption isotherms were applied for
      adsorption of arsenate anions by p(APTMACl) cryogels, and it was observed that
      the adsorption of arsenate anions by p(APTMACl) cryogels are represented better
      via Langmuir adsorption isotherm providing the R(2) value of 0.998. Furthermore,
      mag-p(APTMACl) cryogels were synthesized, and shown to be very useful in the fast
      removal of toxic arsenate anions. The mag-p(APTMACl) cryogels including the
      adsorbed arsenate were removed by an externally applied magnetic field, with some
      reduction in the arsenate ion adsorption capacity. It was also further
      demonstrated that p(APTMACl) cryogels can be reused in the adsorption of arsenate
      5 times from aqueous environments without significant loss of adsorption
      capacity, from 113.47 +/- 9 to 102.67 +/- 6 mg/g. 

PMID- 25617871
TI  - Co-digestion of molasses or kitchen waste with high-rate activated sludge results
      in a diverse microbial community with stable methane production.
AB  - Kitchen waste and molasses are organic waste streams with high organic content,
      and therefore are interesting substrates for renewable energy production by means
      of anaerobic digestion. Both substrates, however, often cause inhibition of the
      anaerobic digestion process, when treated separately, hence, co-digestion with
      other substrates is required to ensure stable methane production. In this
      research, A-sludge (sludge harvested from a high rate activated sludge system)
      was used to stabilize co-digestion with kitchen waste or molasses. Lab-scale
      digesters were fed with A-sludge and kitchen waste or molasses for a total period
      of 105 days. Increased methane production values revealed a stabilizing effect of
      concentrated A-sludge on kitchen waste digestion. Co-digestion of molasses with A
      sludge also resulted in a higher methane production. Volumetric methane
      production rates up to 1.53 L L(-1) d(-1) for kitchen waste and 1.01 L L(-1) d(
      1) for molasses were obtained by co-digestion with A-sludge. The stabilizing
      effect of A-sludge was attributed to its capacity to supplement various
      nutrients. Microbial community results demonstrated that both reactor conditions
      and substrate composition determined the nature of the bacterial community,
      although there was no direct influence of micro-organisms in the substrate
      itself, while the methanogenic community profile remained constant as long as
      optimal conditions were maintained. 

PMID- 25617872
TI  - Adsorptive removal of pharmaceuticals from water by commercial and waste-based
      carbons.
AB  - This work describes the single adsorption of seven pharmaceuticals
      (carbamazepine, oxazepam, sulfamethoxazole, piroxicam, cetirizine, venlafaxine
      and paroxetine) from water onto a commercially available activated carbon and a
      non-activated carbon produced by pyrolysis of primary paper mill sludge. Kinetics
      and equilibrium adsorption studies were performed using a batch experimental
      approach. For all pharmaceuticals, both carbons presented fast kinetics
      (equilibrium times varying from less than 5 min to 120 min), mainly described by
      a pseudo-second order model. Equilibrium data were appropriately described by the
      Langmuir and Freundlich isotherm models, the last one giving slightly higher
      correlation coefficients. The fitted parameters obtained for both models were
      quite different for the seven pharmaceuticals under study. In order to evaluate
      the influence of water solubility, log Kow, pKa, polar surface area and number of
      hydrogen bond acceptors of pharmaceuticals on the adsorption parameters, multiple
      linear regression analysis was performed. The variability is mainly due to log
      Kow followed by water solubility, in the case of the waste-based carbon, and due
      to water solubility in the case of the commercial activated carbon. 

PMID- 25617873
TI  - Reduction of volatile fatty acids and odor offensiveness by anaerobic digestion
      and solid separation of dairy manure during manure storage.
AB  - Volatile fatty acids (VFA) play an important role in the biodegradation of
      organic wastes and production of bioenergy under anaerobic digestion, and are
      related to malodors. However, little is known about the dynamics of VFA during
      dairy manure storage. This study evaluated the characteristics of VFA in dairy
      manure before and after anaerobic co-digestion in a laboratory experiment using
      eight lab-scale reactors. The reactors were loaded with four different types of
      dairy manure: (1) liquid dairy manure from a freestall barn, (2) mixture of dairy
      manure and co-digestion food processing wastes at the inlet of an anaerobic
      digester, (3) effluent from the digester outlet, and (4) the liquid fraction of
      effluent from a solid separator. Four VFA (acetic, propionic, butyric, and 2
      methylbutyric acids) were identified and quantified in weekly manure samples from
      all reactors. Results showed that the dominant VFA was acetic acid in all four
      manure sources. The off-farm co-digestion wastes significantly increased the
      total VFA concentrations and the proportions of individual VFA in the influent.
      The dairy manure under storage demonstrated high temporal and spatial variations
      in pH and VFA concentrations. Anaerobic digestion reduced the total VFA by 86%
      96%; but solid-liquid separation did not demonstrate a significant reduction in
      total VFA in this study. Using VFA as an indicator, anaerobic digestion exhibited
      an effective reduction of dairy manure odor offensiveness. 

PMID- 25617874
TI  - Kinetic, isotherm and thermodynamic studies of amaranth dye biosorption from
      aqueous solution onto water hyacinth leaves.
AB  - The present study explored the kinetics, equilibrium and thermodynamics of
      amaranth (acid red 27) anionic dye (AD) biosorption to water hyacinth leaves
      (LEC). The effect of LEC particle size, contact time, solution pH, initial AD
      concentration and temperature on AD biosorption was studied in batch experiments.
      AD biosorption increased with rising contact time and initial AD concentration,
      and with decreasing LEC particle size and solution pH. Pseudo-second-order
      chemical reaction kinetics provided the best correlation for the experimental
      data. Isotherm studies showed that the biosorption of AD onto LEC closely follows
      the Langmuir isotherm, with a maximum biosorption capacity of about 70 mg g(-1).
      The thermodynamic parameters confirm that AD biosorption by LEC is non
      spontaneous and endothermic in nature. Results indicate that LEC is a strong
      biosorbent capable of effective detoxification of AD-laden wastewaters. 

PMID- 25617875
TI  - Multi-component transport and transformation in deep confined aquifer during
      groundwater artificial recharge.
AB  - Taking an artificial groundwater recharge site in Shanghai, China as an example,
      this study employed a combination of laboratory experiment and numerical modeling
      to investigate the transport and transformation of major solutes, as well as the
      mechanism of associated water-rock interactions in groundwater during artificial
      groundwater recharge. The results revealed that: (1) Major ions in groundwater
      were mainly affected by mixing, ion exchanging (Ca(2+), Mg(2+), Na(+), K(+)), as
      well as dissolution of Calcite, Dolomite. Dissolution of carbonate minerals was
      not entirely dependent on the pattern of groundwater recharge, the reactivity of
      the source water itself as indicated by the sub-saturation with respect to the
      carbonate minerals is the primary factor. (2) Elemental dissolution of As, Cr and
      Fe occurred in aquifer was due to the transformation of subsurface environment
      from anaerobic to aerobic systems. Different to bank filtration recharge or pond
      recharge, the concentration of Fe near the recharge point was mainly controlled
      by oxidation dissolution of Siderite, which was followed by a release of As, Cr
      into groundwater. (3) Field modeling results revealed that the hydro chemical
      type of groundwater gradually changed from the initial Cl-HCO3-Na type to the Cl
      HCO3-Na-Ca type during the recharge process, and its impact radius would reach
      roughly 800 m in one year. It indicated that the recharge pressure (approx. 0.45
      Mpa) would enlarge the impact radius under deep well recharge conditions.
      According to different recharge modes, longer groundwater resident time will
      associate with minerals' fully reactions. Although the concentrations of major
      ions were changing during the artificial recharge process, it did not pose a
      negative impact on the environmental quality of groundwater. The result of trace
      elements indicated that controlling the environment factors (especially Eh, DO,
      flow rate) during the recharge was effective to reduce the potential threats to
      groundwater quality. 

PMID- 25617876
TI  - Evidence supporting a link between dental amalgams and chronic illness, fatigue,
      depression, anxiety, and suicide.
AB  - The purpose of this review is to examine the evidence for a relationship between
      mercury (Hg) exposure from dental amalgams and certain idiopathic chronic
      illnesses--chronic fatigue syndrome (CFS), fibromyalgia (FM), depression,
      anxiety, and suicide. Dental amalgam is a commonly used dental restorative
      material that contains approximately 50% elemental mercury (Hg0) by weight and
      releases Hg0 vapor. Studies have shown that chronic Hg exposure from various
      sources including dental amalgams is associated with numerous health complaints,
      including fatigue, anxiety, and depression--and these are among the main symptoms
      that are associated with CFS and FM. In addition, several studies have shown that
      the removal of amalgams is associated with improvement in these symptoms.
      Although the issue of amalgam safety is still under debate, the preponderance of
      evidence suggests that Hg exposure from dental amalgams may cause or contribute
      to many chronic conditions. Thus, consideration of Hg toxicity may be central to
      the effective clinical investigation of many chronic illnesses, particularly
      those involving fatigue and depression.

PMID- 25617877
TI  - Testosterone and explosive aggression in autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are a set of heterogeneous neurodevelopmental
      conditions, characterized by early-onset difficulties in social communication and
      unusually restricted, repetitive behavior and interests. Children with ASD have a
      high rate of irritability and aggressive symptoms which have significant impact
      on their lives, families and society. The etiology of aggression in humans is
      likely complex and includes both biological and behavioral causes. Biological
      approaches have focused on hormones and neurotransmitters that are hypothesized
      to contribute to the etiology and clinical manifestation of aggressive behavior
      in humans. Testosterone is a male sex hormone and some studies suggest that it
      can play a role in the complex etiology of aggressive behavior. Two specific
      subtypes of aggression have been identified: explosive and non-explosive.
      Explosive aggression is accompanied by a raged affect and is usually more
      dangerous and not immediately responsive to behavioral treatment. In our review
      we would like to provide current findings and discuss potential limitation of
      research in this area. We propose to determine bio-behavioral model of explosive
      aggression in children with ASD which will predict which children will be most
      responsive to potential antiandrogen therapy and behavioral therapy. 

PMID- 25617878
TI  - Sleep disturbances and post-traumatic stress disorder in women.
AB  - Sleep disturbances are found in a majority of individuals diagnosed with
      posttraumatic stress disorder (PTSD). The purpose of this literature review is to
      provide information about PTSD, in addition to assessing sleep quality. Current
      research observes that the lifetime prevalence of PTSD diagnosis in women is
      increasing. Although there are several studies that have been conducted to assess
      PTSD and sleep, there is a gap in the research that pertains to women, PTSD, and
      sleep quality. The current study will compile information on the subject to aid
      in decreasing the gender disparity in PTSD research, which is important for
      treating the entire PTSD population. Using the PubMed and PsycINFO databases, a
      comprehensive search was conducted to find relevant research about sleep
      difficulties and PTSD. Sleep disturbances such as insomnia, re-current
      nightmares, REM sleep dysfunction, and obstructive sleep apnea (OSA) affect sleep
      quality in PTSD patients. The implications of this study suggest that more
      research should be conducted pertaining to women and PTSD with sleep
      difficulties. This research is needed to decrease both PTSD symptoms and sleep
      related disorders. 

PMID- 25617879
TI  - Drug-induced gingival enlargement.
AB  - OBJECTIVES: Side effect of medicamentous treatment in hypertension therapy and
      angina pectoris with calcium channel blockers related to fibrotic gingival
      enlargement were examined. METHODS: In our study we deal with clinico
      histopathological and microbiological knowledge from this field underpinned by
      two case reports treated with antihypertensive therapy using calcium channel
      blockers. In the first case report we were largely concerned with microbiological
      findings from the area of periodontal pseudopockets diagnosed through a DNA
      analysis and appropriate antibiotic therapy. In a patient treated with a
      preparation from amlodipine group we proceeded to a complex treatment involving
      the change of hypertension therapy, introduction of professional and home oral
      hygiene and also following surgical and prosthetico-aesthetic rehabilitation.
      RESULTS: Case Report 1 who was for a long term medicated with a preparation from
      the nifedipine group of antihypertensives we detected the presence of periodontal
      pseudopockets with probing depth of 4 to 7 mm with positive BOP and with marked
      rigid fibrotic gingival enlargement accompanied with considerable foetor ex ore.
      In a patient from the Case Report 2 who was for a long term medicated with a
      preparation from the amlodipine group of antihypertensives with large gingival
      overgrowth angiogenesis was characterized by cuboidal endothelial cell lining. In
      the samples under a layer of stratified epithelium there was present dense
      fibrous connective tissue comprising largely of collagen fiber bundles.
      CONCLUSION: Bacterial composition in the patient with a high degree of gingival
      enlargement and periodontal pseudopockets 4 to 7 mm deep represented a typical
      spectrum of bacteria occuring in chronic forms of periodontitis. However, we
      cannot determine, if such distribution of bacteria was primary before the
      application of nifedipine antihypertensives, or it originated later after the
      formation of typical anaerobic setting of false periodontal pockets.

PMID- 25617880
TI  - Attenuation of autoimmune responses to oxidative specific epitopes, but not
      nitroso-adducts, is associated with a better clinical outcome in Myalgic
      Encephalomyelitis/chronic fatigue syndrome.
AB  - OBJECTIVES: There is evidence that inflammatory, oxidative and nitrosative stress
      (IO&NS) pathways participate in the pathophysiology of a subgroup of patients
      with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Increased IgM
      related autoimmune responses to oxidative specific epitopes (OSEs), including
      malondialdehyde (MDA), oleic acid and phosphatidyl inositol (Pi), and nitroso
      (NO)-adducts, including NO-tryptophan (NOW), NO-arginine and NO-cysteinyl, are
      frequently observed in ME/CFS. Autoimmune responses in ME/CFS may be driven by
      increased bacterial translocation as measured by IgM and IgA responses to LPS of
      gram negative bacteria. METHODS: The aim of this study is to examine whether IgM
      responses to OSEs and NO-adducts are related to a better outcome as measured by
      the Fibromyalgia and Fatigue Rating Scale (FF). 76 ME/CFS patients with initially
      abnormal autoimmune responses were treated with care-as-usual, including
      nutraceuticals with anti-IO&NS effects (NAIOS), such as L-carnitine, coenzyme
      Q10, taurine + lipoic acid, with or without curcumine + quercitine or N-acetyl
      cysteine, zinc + glutamine. RESULTS: We found that use of these NAIOS was
      associated with highly significant reductions in initially increased IgM-mediated
      autoimmune responses to OSEs and NO-adducts. A greater reduction in autoimmune
      responses to OSEs during intake of these NAIOS was associated with a lower FF
      score. Reductions in IgM responses to oleic acid, MDA and Pi, but not in any of
      the NO-adducts, were associated with reductions in severity of illness. These
      associations remained significant after adjusting for possible effects of
      increased bacterial translocation (leaky gut). CONCLUSIONS: Our results show that
      autoimmune responses to OSEs are involved in the pathophysiology of ME/CFS and
      that these pathways are a new drug target in a subgroup of ME/CFS patients.
      Although hypernitrosylation and nitrosative stress play a role in ME/CFS,
      reductions in these pathways are not associated with lowered severity of illness.
      Randomized controlled trials with NAIOS should be carried out in the subgroup of
      ME/CFS patients with initially increased autoimmune responses to OSEs.

PMID- 25617881
TI  - Selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in normal
      pressure hydrocephalus.
AB  - OBJECTIVES: Normal pressure hydrocephalus (NPH) is a treatable neurological
      syndrome developing in the elderly. It is characterized by balance impairment,
      urinary incontinence and dementia development caused by disorders in the
      cerebrospinal fluid (CSF) circulation. The diagnosis can be easily mistaken for
      other neurodegenerative diseases, which are often accompanied by inflammation and
      the production of cytokines. The aim of our study was to determine and compare
      selected CSF and plasma cytokines with respect to their informative value for
      laboratory diagnostics of NPH. METHODS: The levels of IL-1beta, IL-4, IL-6, IL
      10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-gamma, sCD40L
      and TNF-alpha were measured in the CSF and plasma in age-matched subjects with
      NPH (n=20) and controls (n=20) by multiplex assay. RESULTS: CSF IL-1beta, IL-6
      and IL-10 were significantly increased on the 1st day of lumbar drainage in NPH
      (p<0.01). No significant changes were observed in the plasma. The CSF cytokines
      were one to three orders of magnitude higher compared to the plasma. CONCLUSION:
      CSF can better show the neurodegenerative changes in the brain. The cytokines IL
      1beta, IL-6 and IL-10 may be helpful in NPH diagnostics.

PMID- 25617882
TI  - Why do some women prefer submissive men? Hierarchically disparate couples reach
      higher reproductive success in European urban humans.
AB  - OBJECTIVES: Equality between partners is considering a feature of the functional
      partnerships in westernized societies. However, the evolutionary consequences of
      how in-pair hierarchy influences reproduction are less known. Attraction of some
      high-ranking women towards low-ranking men represents a puzzle. METHODS: Young
      urban adults (120 men, 171 women) filled out a questionnaire focused on their
      sexual preference for higher or lower ranking partners, their future in-pair
      hierarchy, and hierarchy between their parents. RESULTS: Human pairs with a
      hierarchic disparity between partners conceive more offspring than pairs of
      equally-ranking individuals, who, in turn, conceive more offspring than pairs of
      two dominating partners. Importantly, the higher reproductive success of
      hierarchically disparate pairs holds, regardless of which sex, male or female, is
      the dominant one. In addition, the subjects preferring hierarchy disparity in
      partnerships were with greater probability sexually aroused by such disparity,
      suggesting that both the partnership preference and the triggers of sexual
      arousal may reflect a mating strategy. CONCLUSION: These results challenge the
      frequently held belief in within-pair equality as a trademark of functional
      partnerships. It rather appears that existence of some disparity improves within
      pair cohesion, facilitating both cooperation between partners and improving the
      pairs' ability to face societal challenges. The parallel existence of
      submissivity-dominance hierarchies within human sexes allows for the parallel
      existence of alternative reproductive strategies, and may form a background for
      the diversity of mating systems observed in human societies. Arousal of
      overemphasized dominance/submissiveness may explain sadomasochistic sex, still
      little understood from the evolutionary psychology point of view.

PMID- 25617883
TI  - Increased oxidative damage to membrane lipids following surgery for breast
      cancer.
AB  - OBJECTIVES: To evaluate the level of oxidative damage to membrane lipids due to
      the breast cancer surgery in the early postoperative period. PATIENTS AND
      METHODS: Blood samples were collected on the preoperative day and 24 hours
      postoperatively in 71 women operated for breast cancer, and preoperatively in 38
      female patients with benign breast tumour. Lipid peroxidation (LPO) in the blood
      samples was estimated by measuring the concentrations of malondialdehyde+4
      hydroxyalkenals (MDA+4-HDA) with spectrophotometry. CLINICAL DATA INCLUDED:
      tumour site, tumour histological findings, cancer stage, grade, tumour volume,
      state of lymph nodes, type of surgery for breast, type of surgery for axilla.
      RESULTS: Blood LPO level was similar in breast cancer patients and benign tumour
      patients (2.01+/-0.46 nmol/ml vs. 1.92+/-0.39 nmol/ml, respectively; p>0.05). In
      cancer patients, MDA+4-HDA increased on the first postoperative day, i.e. from
      2.01+/-0.46 nmol/ml to 2.58+/-0.98 nmol/ml (p=0.0001). In women with benign
      breast tumour, LPO did not relate to the histological finding (p=0.8915). In the
      breast cancer group, preoperative LPO did not correlate with age, tumour volume
      and number of metastatic lymph nodes. Level of MDA+4-HDA was similar in stages
      I/II (2.03+/-0.46 nmol/ml) compared to stages III/IV (1.69+/-0.26 nmol/ml,
      p=0.1521). Consequently, levels of MDA+4-HDA did not relate to disease stage
      (p=0.1364). CONCLUSIONS: Surgery for breast cancer causes peripheral increase in
      oxidative damage to macromolecules in the early postoperative period. Therefore,
      perioperative antioxidant supplementation should be considered.

PMID- 25617884
TI  - CT density decrease in water intoxication rat model of brain oedema.
AB  - OBJECTIVES: The aim of this study was to determine whether water intoxication
      affects the radiodensity of brain tissue in CT scan examination in the rat model
      of brain oedema. METHODS: A standard CT scan of the brain was obtained in a group
      of rats, first at control conditions (controls - CG) and then after
      hyperhydration (oedema model-EG) in the region of interest (ROI) corresponding to
      the area of coronary sections with pixel size 0.125 mm in position A (bregma
      +2.43 mm), position B (bregma -2.92 mm), position C (bregma -12.73 mm).
      Densitometrically determined mean values (MV), expressed in Hounsfield units (HU)
      were processed by standard statistical methods. RESULTS: The average MV density
      was 120.49+/-6.79 HU for the control measurement and 88.01+/-4.72 HU after the
      hyperhydration, which represents decrease in the density by 32.48 HU (p<0.001).
      In the control measurement the average value of HU for the position A was 121.98,
      for position B 112.4 and for position C 127.08. In conditions of hyperhydration,
      the average MV density in position A was 89.95 HU in position B 84.67 HU and in
      position C 89.43 HU. The differences between the CG and EG were in all positions
      A, B, C statistically significant (p<0.001). In the control measurement, the
      differences between position A*B (p<0.05) and B*C (p<0.001) were statistically
      significant. After hyperhydration no significant difference between the position
      A, B, C was found. CONCLUSION: water intoxication caused by hyperhydration in
      rats can induce diffuse brain oedema, which is reflected in the CT examination by
      the decrease of brain tissue density, expressed in HU. The value of the measured
      density depends on the location and size of the measured brain area.

PMID- 25617885
TI  - Complications of MRI-guided stereotactic biopsy of brain lymphoma.
AB  - OBJECTIVES: Stereotactic biopsy is a suitable method for sampling intrinsic brain
      lesions. Although this method is considered to be a safe procedure, some risk of
      complications still exists. The aim of the study was to retrospectively assess
      the morbidity and mortality of MRI-guided stereotactic biopsy of lesions which
      were histologically proven to be brain lymphoma. METHODS: We retrospectively
      studied all accessible medical records for patients who had undergone MRI-guided
      stereotactic biopsy of brain lesions with histologically proven brain lymphoma
      from January 2007 to December 2012. Our cohort included 45 patients, 27 males and
      18 females, aged 23-84 (63+/-14) years. RESULTS: Forty-nine biopsies were carried
      out on 45 patients; the average number of tissue specimens was 3+/-1. The
      diagnostic yield of the stereotactic biopsy was 92%. Overall major morbidity
      directly related to stereotactic biopsy of brain lymphoma was 6.1% (3 cases)
      including 4.1% mortality (2 cases). Both deaths after the stereotactic procedure
      were due to intracranial hemorrhage and subsequent complications and both these
      patients had a history of treatment of systemic lymphomas. In one patient the
      stereotactic biopsy was complicated by a brain abscess which was successfully
      treated. CONCLUSION: Stereotactic biopsy is still a mandatory diagnostic
      procedure for primary brain lymphomas, with an acceptable risk of complications.
      However, according to our results, the risk of complications can be higher in
      patients who have previously been treated for secondary lymphomas.

PMID- 25617886
TI  - Detection of methylation of the promoter region of the MAL and CADM1 genes by
      pyrosequencing in cervical carcinoma.
AB  - OBJECTIVE: Cervical cancer is the second most common cancer disease affecting the
      female population. A key factor in development of the disease is the human
      papillomavirus infection (HPV). The disease is also impacted by epigenetic
      changes such as DNA methylation, which causes activation or exclusion of certain
      genes, and simultaneously the hypermethylation of cytosines in the promoters and
      turn-off of previously active genes occur. In this study, we focused on the
      introduction of pyrosequencing for the detection of DNA methylation of the
      selected CADM1 and MAL genes. METHODS: DNA was isolated from cytological cervical
      smear of patients with different types of dysplasia [L-SIL (n=14), ASC-US (n=15),
      H-SIL (n=1)] and four control samples from healthy women. Prepared samples were
      further analyzed by bisulfite conversion and subsequent pyrosequencing (Pyromark
      Q96 ID, Qiagen, Germany). We examined the extent of methylation of CpG islands
      and as control samples of this method we used a fully methylated and unmethylated
      DNA. Methylation level (Met level) from each sample was quantified as the mean
      value [sum of all methylated CpG islands in %/total number of CpG islands (MAL
      n=4; CADM1 n=3)]. RESULTS: In total, 30 clinical samples and 4 control samples
      from healthy women were analyzed. By means of the analysis of the CADM1promoter
      region, the values of the Met level were obtained [fully methylated DNA (94.83
      and 88); completely unmethylated DNA (0 and 0); and control samples from healthy
      patients (6.825 and 0.825), L-SIL (2.107 and 2.778), ASC-US (7.313 and 3.626), H
      SIL (0 and 0)]. By means of the analysis of the MAL promoter region, the values
      of Met level were obtained [fully methylated DNA (53.25); completely unmethylated
      DNA (0.875); and control samples from healthy patients (2.925), L-SIL (1.517),
      ASC-US (2.833), and H-SIL (4)]. CONCLUSION: We introduced a pyrosequencing method
      for quantification of methylation of CADM1, MAL promoter regions, and detected
      methylations in clinical samples and also some basal methylation in healthy
      women.

PMID- 25617887
TI  - Self-stigma in psychiatric patients--standardization of the ISMI scale.
AB  - OBJECTIVE: Self-stigma in psychiatric patients is an issue deserving both
      research and therapeutic attention. The objective of the present study was to
      evaluate the psychometric properties of a Czech version of the Internalized
      Stigma of Mental Illness (ISMI) scale assessing the levels of self-stigma in
      individuals with mental disorders. METHODS: It consists of 29 items classified
      into 5 subscales, namely alienation, stereotype endorsement, perceived
      discrimination, social withdrawal and stigma resistance. The study group
      comprised 369 patients with a mean age of 41.5+/-13.3 years, of whom 210 (56.6%)
      were females. RESULTS: The most frequent diagnosis was neurotic disorders
      (46.1%), followed by affective disorders (18.4%), substance use disorders
      (13.3%), psychotic disorders (10.8%), personality disorders (9.5%) and organic
      disorders (1.6%). Reliability of the scale was evaluated by internal consistency
      analysis (alpha=0.91), the split-half method (Spearman-Brown coefficient: 0.93)
      and test-retest at 3 weeks from the first measurement (N=17; r=0.90, p<0.05).
      CONCLUSION: Exploratory factor analysis of the scale was performed, its validity
      was verified and norms were established that were based on T-scores and sten
      scores for the entire scale and individual subscales. The Czech translation of
      the ISMI has adequate psychometric properties.

PMID- 25617888
TI  - Knee joint muscles neuromuscular activity during load-carrying walking.
AB  - OBJECTIVE: To investigate the effects of increasing load on changes in the muscle
      activity ratio and onset of vastus medialis (VM), vastus lateralis (VL) and
      biceps femoris (BF) during load-carrying walking. MATERIALS AND METHODS: Sixteen
      strength-trained men performed an isometric test for knee flexion/extension using
      a dynamometer followed by walking with progressively increasing loads of up to
      75% of their body mass (BM). During the isometric tests and load-carrying
      walking, electromyography (EMG) data were collected from the VM, VL and BF in
      both legs together with 3D kinematics. RESULTS: Significant changes in the
      activity ratio were found for the VM/VL (F3,93=5.92, p=0.0001) and VL onset
      (F3,81=6.8, p=0.0004). Other parameters showed no significant differences. VM/VL
      was significantly reduced between the 50BM (mean+/-SD: 0.89+/-0.4) and the 75BM
      condition (0.81+/-0.3). VL onset was significantly accelerated between the BM
      (26.11+/-8) compare and the 25% BM (19.47+/-9), 50% BM (21.21+/-10) and 75% BM
      (15.45+/-6) conditions. CONCLUSION: Load-carrying walking is an exercise and
      movement activity that increases the activity of VL more than the activity of VM
      and accelerates the VL action together with the increased load, which can
      negatively influence knee stability. The VM/VL ratio and onset is equal when
      walking under weight-bearing conditions. The inter-muscular coordination is
      changed due to the increased load in complex movements even in individuals with
      high level of neuromuscular adaptation.

PMID- 25617889
TI  - Evaluation of adipocytokine levels and vascular functions in young aged to middle
      aged men with idiopathic hypogonadotrophic hypogonadism.
AB  - OBJECTIVE: Hypogonadism has major effects on the urogenital system, in addition
      to other systems, the cardiovascular system in particular. There have been few
      studies conducted on markers of atherosclerosis, such as flow mediated dilatation
      (% FMD), carotid intima-media thickness (CIMT) and adipocytokine levels in
      idiopatic hypogonadotropic hypogonadal (IHH) males mostly in adult patients. The
      aim of this study was to evaluate the relationship between androgens and
      adipocytokines and parameters of vascular functions in hypogonadal men. MATERIALS
      AND METHODS: The study population consisted of 11 treatment naive IHH patients
      (group 1) and 15 age-matched healthy control males (group 2). A fasting blood
      sample was obtained for leptin, adiponectin and resistin. The endothelial
      functions were evaluated by studying % FMD and CIMT by high resolution B-mode
      ultrasound. RESULTS: No significant differences in age, body mass index, systolic
      and diastolic blood pressure were recorded between the two groups. The leptin
      level was significantly higher in group 1, whereas adiponectin and resistin
      levels were same between two groups. There was a negative correlation between
      total testosterone and carotid intima-media thickness (r=-0.656, p=0.008), and a
      negative correlation between total testosterone and leptin level (r=-0.794,
      p<0.001). No correlation was found between leptin and CIMT (p=0.184). CONCLUSION:
      Testosterone deficiency in hypogonadal men is associated with vascular parameters
      of atherosclerosis. The findings may establish indications for testosterone
      replacement therapy in hypogonadal men.

PMID- 25617890
TI  - Self-stigma and adherence to medication in patients with psychotic disorders-
      cross-sectional study.
AB  - OBJECTIVE: Adherence to treatment of mental disorders is one of the key factors
      influencing its success and, secondarily, the patients' quality of life and
      social adaptation. The cross-sectional study of 90 outpatients diagnosed with
      psychotic disorders aimed at determining if there was a relationship between
      discontinuation of psychoactive drugs in the past, current adherence to treatment
      and self-stigma. METHODS: The assessment was made with the objective and
      subjective Clinical Global Impression - Severity scale, Drug Attitude Inventory,
      Internalized Stigma of Mental Illness (ISMI) scale and demographic data. The
      questionnaires were filled out by 79 patients, of whom 5 handed in incomplete
      questionnaires. Complete sets of data were obtained from 74 patients. RESULTS:
      The data analysis showed that the levels of self-stigma as assessed by the total
      ISMI scores was not statistically significantly correlated with most of the
      demographic factors (age, age of illness onset, gender, education, marital
      status, employment, duration of the illness, number of hospitalizations and
      antipsychotic dosage). However, there was a significant negative correlation with
      current adherence to treatment.

PMID- 25617891
TI  - Swelling/floating capability and drug release characterizations of
      gastroretentive drug delivery system based on a combination of hydroxyethyl
      cellulose and sodium carboxymethyl cellulose.
AB  - The aim of this study was to characterize the swelling and floating behaviors of
      gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose
      (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS
      to incorporate three model drugs with different solubilities (metformin,
      ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated,
      and their swelling and floating behaviors were characterized. Influences of media
      containing various NaCl concentrations on the swelling and floating behaviors and
      drug solubility were also characterized. Finally, release profiles of the three
      model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined.
      Results demonstrated when the GRDDS tablets were tested in simulated gastric
      solution, the degree of swelling at 6 h was decreased for each formulation that
      contained NaCMC in comparison to those in de-ionized water (DIW). Of note,
      floating duration was enhanced when in simulated gastric solution compared to
      DIW. Further, the hydration of tablets was found to be retarded as the NaCl
      concentration in the medium increased resulting in smaller gel layers and
      swelling sizes. Dissolution profiles of the three model drugs in media containing
      various concentrations of NaCl showed that the addition of NaCl to the media
      affected the solubility of the drugs, and also their gelling behaviors, resulting
      in different mechanisms for controlling a drug's release. The release mechanism
      of the freely water-soluble drug, metformin, was mainly diffusion-controlled,
      while those of the water-soluble drug, ciprofloxacin, and the slightly water
      soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results
      showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps
      possessed proper swelling extents and desired floating periods with sustained
      release characteristics. 

PMID- 25617892
TI  - How bees discriminate a pattern of two colours from its mirror image.
AB  - A century ago, in his study of colour vision in the honeybee (Apis mellifera),
      Karl von Frisch showed that bees distinguish between a disc that is half yellow,
      half blue, and a mirror image of the same. Although his inference of colour
      vision in this example has been accepted, some discrepancies have prompted a new
      investigation of the detection of polarity in coloured patterns. In new
      experiments, bees restricted to their blue and green receptors by exclusion of
      ultraviolet could learn patterns of this type if they displayed a difference in
      green contrast between the two colours. Patterns with no green contrast required
      an additional vertical black line as a landmark. Tests of the trained bees
      revealed that they had learned two inputs; a measure and the retinotopic position
      of blue with large field tonic detectors, and the measure and position of a
      vertical edge or line with small-field phasic green detectors. The angle between
      these two was measured. This simple combination was detected wherever it occurred
      in many patterns, fitting the definition of an algorithm, which is defined as a
      method of processing data. As long as they excited blue receptors, colours could
      be any colour to human eyes, even white. The blue area cue could be separated
      from the green receptor modulation by as much as 50 degrees . When some blue
      content was not available, the bees learned two measures of the modulation of the
      green receptors at widely separated vertical edges, and the angle between them.
      There was no evidence that the bees reconstructed the lay-out of the pattern or
      detected a tonic input to the green receptors. 

PMID- 25617893
TI  - Detrusor induction of miR-132/212 following bladder outlet obstruction:
      association with MeCP2 repression and cell viability.
AB  - The microRNAs (miRNAs) miR-132 and miR-212 have been found to regulate synaptic
      plasticity and cholinergic signaling and recent work has demonstrated roles
      outside of the CNS, including in smooth muscle. Here, we examined if miR-132 and
      miR-212 are induced in the urinary bladder following outlet obstruction and
      whether this correlates with effects on gene expression and cell growth. Three to
      seven-fold induction of miR-132/212 was found at 10 days of obstruction and this
      was selective for the detrusor layer. We cross-referenced putative binding sites
      in the miR-132/212 promoter with transcription factors that were predicted to be
      active in the obstruction model. This suggested involvement of Creb and Ahr in
      miR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the
      number of Ahr positive nuclei increased. Moreover, we found that serum
      stimulation and protein kinase C activation induced miR-132/212 in human detrusor
      cells. To identify miR-132/212 targets, we correlated the mRNA levels of
      validated targets with the miRNA levels. Significant correlations between miR
      132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels
      of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however
      closely matched a 90% reduction of synapse density arguing that its repression
      was unrelated to miR-132/212 induction. Importantly, transfection of antimirs and
      mimics in cultured detrusor cells increased and decreased, respectively, the
      number of cells and led to changes in MeCP2 expression. In all, these findings
      show that obstruction of the urethra increases miR-132 and miR-212 in the
      detrusor and suggests that this influences gene expression and limits cell
      growth. 

PMID- 25617894
TI  - N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in
      astroglia-like cells.
AB  - Cocaine has a short half-life of only about an hour but its effects,
      predominantly on the central nervous system (CNS), are fairly long-lasting. Of
      all cells within the CNS, astrocytes may be the first to display cocaine toxicity
      owing to their relative abundance in the brain. Cocaine entry could trigger
      several early response changes that adversely affect their survival, and
      inhibiting these changes could conversely increase their rate of survival. In
      order to identify these changes and the minimal concentrations of cocaine that
      can elicit them in vitro, rat C6 astroglia-like cells were treated with cocaine
      (2-4 mM for 1h) and assayed for alterations in gross cell morphology, cytoplasmic
      vacuolation, viability, reactive oxygen species (ROS) generation, glutathione
      (GSH) levels, cell membrane integrity, F-actin cytoskeleton, and histone
      methylation. We report here that all of the above identified features are
      significantly altered by cocaine, and may collectively represent the key
      pathology underlying acute toxicity-mediated death of astroglia-like cells.
      Pretreatment of the cells with the clinically available antioxidant N-acetyl
      cysteine (NAC, 5 mM for 30 min) inhibited these changes during subsequent
      application of cocaine and mitigated cocaine-induced toxicity. Despite repeated
      cocaine exposure, NAC pretreated cells remained highly viable and post NAC
      treatment also increased viability of cocaine treated cells to a smaller yet
      significant level. We show further that this alleviation by NAC is mediated
      through an increase in GSH levels in the cells. These findings, coupled with the
      fact that astrocytes maintain neuronal integrity, suggest that compounds which
      target and mitigate these early toxic changes in astrocytes could have a
      potentially broad therapeutic role in cocaine-induced CNS damage. 

PMID- 25617895
TI  - Common variants related to serum uric acid concentrations are associated with
      glucose metabolism and insulin secretion in a Chinese population.
AB  - BACKGROUND: Elevated serum uric acid concentration is an independent risk factor
      and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes
      have an impact on T2D remains unclear. We aimed to investigate the effects of the
      uric acid-associated genes on the risk of T2D as well as glucose metabolism and
      insulin secretion. METHOD: We recruited 2,199 normal glucose tolerance subjects
      from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the
      inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide
      polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2,
      LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum
      biochemical parameters related to uric acid and T2D were determined. RESULTS: SF1
      rs606458 showed strong association to T2D in both males and females (p = 0.034
      and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin
      secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin
      secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose
      (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations
      with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052
      and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated
      with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049,
      respectively). CONCLUSIONS: Our results indicated that the uric acid-associated
      genes have an impact on the risk of T2D, glucose metabolism and insulin secretion
      in a Chinese population.

PMID- 25617896
TI  - Usefulness of a fourth generation ELISA assay for the reliable identification of
      HCV infection in HIV-positive adults from Gabon (Central Africa).
AB  - BACKGROUND/OBJECTIVES: Guidelines for optimized HCV screening are urgently
      required in Africa, especially for patients infected with HIV, who sometimes show
      false positive or false negative reactivity in anti-HCV antibody assays. Here, we
      assessed the usefulness of a fourth-generation HCV Ag-Ab ELISA for the
      identification of active HCV infection in HIV-positive patients. METHODS: This
      cross-sectional study was conducted between 03/2010 and 01/2013 and included 762
      Gabonese HIV-positive adult patients. The results of ELISA (Monolisa HCV Ag-Ab
      ULTRA, Bio-Rad) were compared with those obtained by RT-PCR (gold standard). The
      optimal ELISA signal-to-cutoff (S/CO) ratio to identify patients with active
      hepatitis C (positive HCV RNA) was determined. Specimens were further tested by
      the INNO-LIA HCV Score assay (Innogenetics) and the Architect HCV Ag kit (Abbott)
      to define the best diagnostic strategy. RESULTS: Sixty-seven patients tested
      positive for HCV (S/CO ratio >= 1) by ELISA. Of these, 47 (70.1%) tested positive
      for HCV RNA. The optimal S/CO associated with active HCV infection was 1.7. At
      this threshold, the sensitivity of ELISA was 97.9% (95% confidence interval (CI)
      90.0-99.9%), its specificity was 91.3% (95% CI 85.0-95.5%), and HCV
      seroprevalence rate was 7.3% (56/762) (95% CI 5.6-9.4%). Among 57 HCV
      seropositive patients with available INNO-LIA results, false reactivity was
      identified in 14 (24.6%), resolved HCV infection in two (3.5%), possible acute
      HCV infections in nine (15.8%) and likely chronic HCV infections in 32 (56.1%)
      patients. HCV core Ag was undetectable in 14/15 (93.3%) specimens that tested
      negative for HCV RNA whereas it was quantified in 34 (out of 39, 87.2%) samples
      that tested positive for HCV RNA. CONCLUSIONS: Our study provides comprehensive
      guidance for HCV testing in Gabon, and will help greatly clinicians to improve
      case definitions for both the notification and surveillance of HCV in patients co
      infected with HIV.

PMID- 25617897
TI  - Dietary Enterococcus faecalis LAB31 improves growth performance, reduces
      diarrhea, and increases fecal Lactobacillus number of weaned piglets.
AB  - Lactic acid bacteria (LAB) have been shown to enhance performance of weaned
      piglets. However, few studies have reported the addition of LAB Enterococcus
      faecalis as alternatives to growth promoting antibiotics for weaned piglets. This
      study evaluated the effects of dietary E. faecalis LAB31 on the growth
      performance, diarrhea incidence, blood parameters, fecal bacterial and
      Lactobacillus communities in weaned piglets. A total of 360 piglets weaned at 26
      +/- 2 days of age were randomly allotted to 5 groups (20 pens, with 4 pens for
      each group) for a trial of 28 days: group N (negative control, without
      antibiotics or probiotics); group P (Neomycin sulfate, 100 mg/kg feed); groups L,
      M and H (supplemented with E. faecalis LAB31 0.5*109, 1.0*109, and 2.5*109 CFU/kg
      feed, respectively). Average daily gain and feed conversion efficiency were found
      to be higher in group H than in group N, and showed significant differences
      between group H and group P (P0 < 0.05). Furthermore, groups H and P had a lower
      diarrhea index than the other three groups (P0 < 0.05). Denaturing gradient gel
      electrophoresis (DGGE) showed that the application of probiotics to the diet
      changed the bacterial community, with a higher bacterial diversity in group M
      than in the other four groups. Real-time PCR revealed that the relative number of
      Lactobacillus increased by addition of probiotics, and was higher in group H than
      in group N (P0 < 0.05). However, group-specific PCR-DGGE showed no obvious
      difference among the five groups in Lactobacillus composition and diversity.
      Therefore, the dietary addition of E. faecalis LAB31 can improve growth
      performance, reduce diarrhea, and increase the relative number of Lactobacillus
      in feces of weaned piglets. 

PMID- 25617898
TI  - Mertk deficiency affects macrophage directional migration via disruption of
      cytoskeletal organization.
AB  - Mertk belongs to the Tyro3, Axl and Mertk (TAM) family of receptor tyrosine
      kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement
      during phagocytosis. Phagocytosis by either professional or non-professional
      phagocytes is impaired in the Mertk deficient individual. In the present study,
      we further investigated the effects of Mertk mutation on peritoneal macrophage
      morphology, attachment, spreading and movement. Mertk-mutated macrophages
      exhibited decreased attachment, weak spreading, loss of spindle-like body shape
      and lack of clear leading and trailing edges within the first few hours of
      culture, as observed by environmental scanning electron microscopy. Time-lapse
      video photography recording showed that macrophage without Mertk conducted mainly
      random movement with oscillating swing around the cell body, and lost the
      directional migration action seen on the WT cells. Western blotting showed a
      decreased phosphorylation of focal adhesion kinase (FAK). Immunocytochemistry
      revealed that actin filaments and dynamic protein myosin II failed to concentrate
      in the leading edge of migrating cells. Microtubules were localized mainly in one
      side of mutant cell body, with no clear MTOC and associated radially-distributed
      microtubule bundles, which were clearly evident in the WT cells. Our results
      suggest that Mertk deficiency affects not only phagocytosis but also cell shape
      and migration, likely through a common regulatory mechanism on cytoskeletons. 

PMID- 25617899
TI  - Enhanced amphiphilic profile of a short beta-stranded peptide improves its
      antimicrobial activity.
AB  - SB056 is a novel semi-synthetic antimicrobial peptide with a dimeric dendrimer
      scaffold. Active against both Gram-negative and -positive bacteria, its mechanism
      has been attributed to a disruption of bacterial membranes. The branched peptide
      was shown to assume a beta-stranded conformation in a lipidic environment. Here,
      we report on a rational modification of the original, empirically derived linear
      peptide sequence [WKKIRVRLSA-NH2, SB056-lin]. We interchanged the first two
      residues [KWKIRVRLSA-NH2, beta-SB056-lin] to enhance the amphipathic profile, in
      the hope that a more regular beta-strand would lead to a better antimicrobial
      performance. MIC values confirmed that an enhanced amphiphilic profile indeed
      significantly increases activity against both Gram-positive and -negative
      strains. The membrane binding affinity of both peptides, measured by tryptophan
      fluorescence, increased with an increasing ratio of negatively
      charged/zwitterionic lipids. Remarkably, beta-SB056-lin showed considerable
      binding even to purely zwitterionic membranes, unlike the original sequence,
      indicating that besides electrostatic attraction also the amphipathicity of the
      peptide structure plays a fundamental role in binding, by stabilizing the bound
      state. Synchrotron radiation circular dichroism and solid-state 19F-NMR were used
      to characterize and compare the conformation and mobility of the membrane bound
      peptides. Both SB056-lin and beta-SB056-lin adopt a beta-stranded conformation
      upon binding POPC vesicles, but the former maintains an intrinsic structural
      disorder that also affects its aggregation tendency. Upon introducing some
      anionic POPG into the POPC matrix, the sequence-optimized beta-SB056-lin forms
      well-ordered beta-strands once electro-neutrality is approached, and it
      aggregates into more extended beta-sheets as the concentration of anionic lipids
      in the bilayer is raised. The enhanced antimicrobial activity of the analogue
      correlates with the formation of these extended beta-sheets, which also leads to
      a dramatic alteration of membrane integrity as shown by 31P-NMR. These findings
      are generally relevant for the design and optimization of other membrane-active
      antimicrobial peptides that can fold into amphipathic beta-strands. 

PMID- 25617900
TI  - A novel therapy to attenuate acute kidney injury and ischemic allograft damage
      after allogenic kidney transplantation in mice.
AB  - Ischemia followed by reperfusion contributes to the initial damage to allografts
      after kidney transplantation (ktx). In this study we tested the hypothesis that a
      tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney
      function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia
      induced delayed graft function after allogenic kidney transplantation. IRI was
      induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for
      35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive
      days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already
      established. The treatment resulted in markedly improved survival in a dose
      dependent manner. Acute tubular injury two days after IRI was diminished and
      tubular epithelial cell proliferation was significantly enhanced by EA-230
      treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis,
      at four weeks after IRI was significantly less in EA-230 treated renal tissue. To
      learn more about these effects, we measured renal blood flow (RBF) and glomerular
      filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF
      significantly. Next, EA-230 treatment was tested in a model of ischemia-induced
      delayed graft function after allogenic kidney transplantation. The recipients
      were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal
      function and allograft survival by attenuating ischemic allograft damage. In
      conclusion, EA-230 is a novel and promising therapeutic agent for treating acute
      kidney injury and preventing IRI-induced post-transplant ischemic allograft
      injury. Its beneficial effect is associated with improved renal perfusion after
      IRI and enhanced regeneration of tubular epithelial cells. 

PMID- 25617901
TI  - Epidural sustained release ropivacaine prolongs anti-allodynia and anti
      hyperalgesia in developing and established neuropathic pain.
AB  - Ropivacaine is a local anesthetic widely used for regional anesthesia and
      epidural analgesia, but its relatively short duration limits its clinical use. A
      novel sustained release lipid formulation of ropivacaine has been recently
      developed to prolong its duration. We examined the epidural anti-hypersensitivity
      and preemptive effects of ropivacaine in mesylate injection and sustained release
      suspension forms in a rat model of neuropathy produced by peripheral nerve
      injury. Epidural administration of ropivacaine mesylate injection specifically
      blocked mechanical allodynia and thermal hyperalgesia by approximately 50% with a
      biological half-effective duration of approximately 3 hrs. The equivalent dose of
      ropivacaine free-base in sustained release suspension significantly prolonged the
      duration of anti-allodynia and anti-hyperalgesia by approximately 2 times.
      Multiple daily epidural injections of ropivacaine in both the mesylate injection
      and sustained-release suspension forms did not induce tolerance or potentiation
      to anti-allodynia or anti-hyperalgesia. Moreover, the single or multiple daily
      administration of ropivacaine mesylate injection before surgery in particular,
      markedly blocked the initiation and development of neuropathic pain, increasing
      the biological half-effective duration from less than 4 hrs up to 1 or 2 days.
      The single and multiple daily epidural injection of ropivacaine sustained release
      suspension further delayed the biological half-lives to 2 and 3 days,
      respectively. Our results indicate that the epidural administration of
      ropivacaine effectively blocks neuropathic pain without the induction of
      analgesic tolerance, and significantly delays the development of neuropathy
      produced by peripheral nerve injury. Epidural ropivacaine sustained release
      suspension produces much longer blockade effects of mechanical allodynia and heat
      hyperalgesia, and more significantly delays the development of neuropathic pain. 

PMID- 25617902
TI  - Arthritis induces early bone high turnover, structural degradation and mechanical
      weakness.
AB  - BACKGROUND: We have previously found in the chronic SKG mouse model of arthritis
      that long standing (5 and 8 months) inflammation directly leads to high collagen
      bone turnover, disorganization of the collagen network, disturbed bone
      microstructure and degradation of bone biomechanical properties. The main goal of
      the present work was to study the effects of the first days of the inflammatory
      process on the microarchitecture and mechanical properties of bone. METHODS:
      Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during
      22 days after disease induction for the inflammatory score, ankle perimeter and
      body weight. Healthy non-arthritic rats were used as controls for compar-ison.
      After 22 days of disease progression rats were sacrificed and bone samples were
      collected for histomorphometrical, energy dispersive X-ray spectroscopical
      analysis and 3-point bending. Blood samples were also collected for bone turnover
      markers. RESULTS: AIA rats had an increased bone turnover (as inferred from
      increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was
      paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p =
      0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and
      bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the
      arthritic group as compared with controls. In addition, bone mechanical tests
      showed evidence of fragility as depicted by diminished values of yield stress and
      ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the
      arthritic group. CONCLUSIONS: We have shown in an AIA rat model that arthritis
      induc-es early bone high turnover, structural degradation, mineral loss and
      mechanical weak-ness.

PMID- 25617903
TI  - PBT assessment and prioritization by PBT Index and consensus modeling: comparison
      of screening results from structural models.
AB  - The limited availability of comprehensive data for Persistence, Bioaccumulation
      and Toxicity (PBT) of chemicals is a serious hindrance to the assignment of
      compounds to the categories of PBT and vPvB; REACH regulation requires
      authorization for the use of such chemicals, and additionally plans for safer
      alternatives. In the context of screening and priority-setting tools for PBT
      assessment, the cumulative PBT Index model, implemented in QSARINS (QSAR
      INSUBRIA), new software tool for the development and validation of multiple
      linear regression QSAR models, offers a new holistic approach for the
      identification of chemicals with cumulative PBT properties directly from their
      molecular structure. In this study the Insubria PBT Index in QSARINS is applied
      to the screening and prioritization of various data sets, containing a large
      variety of chemicals of heterogeneous molecular structure, previously screened by
      various authors by different methods, for their potential PBT behavior.
      Particular attention is devoted to the model Applicability Domain, using
      different approaches such as Descriptor Range, Leverage, and Principal Component
      Analysis (PCA) of the modeling molecular descriptors, in order to discriminate
      between interpolated and extrapolated predictions. The results of this screening,
      which is based only on the molecular structure features and is not dependent on
      single threshold values for P, B and T, are compared with those obtained by the
      on-line US-EPA PBT Profiler. Good agreement between the various approaches is
      found, supporting the utility of a consensus approach in priority-setting
      studies. The main discrepancies are highlighted and commented on. Moreover, a
      priority list containing the most hazardous compounds identified in agreement
      between the two tools is drafted. The PBT Index, implemented in QSARINS, which
      was demonstrated to be a practical, precautionary and reliable screening tool for
      PBT-behavior directly from the molecular structure, can be usefully applied for
      focusing experimental studies, and even before chemical synthesis, in a "benign
      by design" approach of safer alternatives. 

PMID- 25617904
TI  - An observational study on adrenal insufficiency in a French tertiary centre: Real
      life versus theory.
AB  - BACKGROUND: Patients suffering from adrenal insufficiency, whether primary (PAI)
      or secondary (SAI) have an increased mortality risk and increased morbidity.
      There are no guidelines on hydrocortisone replacement therapy and little is known
      on patients' management in current practice. We described patients' profiles and
      treatment in a tertiary referral centre. METHODS: Data were collected
      retrospectively from medical charts. PAI and SAI patients were described and
      compared. RESULTS: Two hundred and one patients (79 PAI+122 SAI) were included.
      They had a mean duration of disease of 11.2years. Main causes of PAI were
      autoimmune diseases (31%) and adrenalectomy (26%). SAI was caused primarily by
      pituitary tumors (61%) and irradiation (20%). Mean dose of daily hydrocortisone
      (HC) was 27.5 and 19.9mg/day in PAI and SAI patients respectively, with a
      majority of patients dividing the dose into 2 intakes (46.8 and 72.2% in PAI and
      SAI groups, respectively). SAI patients exhibited more cardiovascular risk
      factors than PAI patients. The HC daily dose was slightly higher in patients with
      dyslipidemia (in both PAI and SAI groups) and in those with high blood pressure
      (in the SAI group only). One third of patients were out of work, due to
      unemployment, sick leaves, or disability. CONCLUSIONS: The management of AI is
      far from standardized, and individual tailorization is difficult with currently
      available means of treatment. Under- and overdose of hydrocortisone likely leads
      to complications, and altered quality of life reflected by a high rate of "out of
      work" patients.

PMID- 25617905
TI  - Evaluation of the measurement uncertainty in screening immunoassays in blood
      establishments: computation of diagnostic accuracy models.
AB  - The European Union regulation for blood establishments does not require the
      evaluation of measurement uncertainty in virology screening tests, which is
      required by ISO 15189 guideline following GUM principles. GUM modular approaches
      have been discussed by medical laboratory researchers but no consensus has been
      achieved regarding practical application. Meanwhile, the application of empirical
      approaches fulfilling GUM principles has gained support. Blood establishments'
      screening tests accredited by ISO 15189 need to select an appropriate model even
      GUM models are intended uniquely for quantitative examination procedures.
      Alternative (to GUM) models focused on probability have been proposed in medical
      laboratories' diagnostic tests. This article reviews, discusses and proposes
      models for diagnostic accuracy in blood establishments' screening tests. The
      output of these models is an alternative to VIM's measurement uncertainty
      concept. Example applications are provided for an anti-HCV test where
      calculations were performed using a commercial spreadsheet. The results show that
      these models satisfy ISO 15189 principles and that the estimation of clinical
      sensitivity, clinical specificity, binary results agreement and area under the
      ROC curve are alternatives to the measurement uncertainty concept. 

PMID- 25617906
TI  - [Multidisciplinary management of retinoblastoma: Experience in 37 eyes].
AB  - OBJECTIVE: To report the results of the multidisciplinary management of patients
      with retinoblastoma, including survival, enucleation rate, and systemic
      chemoreduction success. METHODS: A retrospective study was conducted on 27
      patients (37 eyes) diagnosed with retinoblastoma, and treated by a
      multidisciplinary team in San Juan de Dios Hospital. Demographic information,
      clinical characterization, survival, local and systemic treatments were included
      in the analysis. Patients treated with intra-arterial chemotherapy (IAC) were
      also reviewed. RESULTS: The study included14 male patients (52%). The median of
      age at presentation was 8 months (0.16-90). The median follow-up time was 33 +/-
      21 months. The diagnosis was made in 10 (37%) cases after 15 months old, with a
      median of 35 months (24-90). 17 (63%) patients had unilateral retinoblastoma, and
      10 (37%) bilateral retinoblastoma. Leukocoria, isolated or associated with other
      signs, was the most frequent reason for referral (63%). Global enucleation rate
      was 57% (n=21), being the primary treatment in 15 (55%) patients. Enucleation
      rate in unilateral retinoblastoma was 76.5%, and for bilateral retinoblastoma, it
      was 60% for one eye and 10% for both. Systemic chemotherapy was prescribed in 17
      (63%) patients, with a mean number of cycles of 5.3 +/- 2.1. The overall success
      of chemoreduction and focal therapy in order to avoid external radiotherapy
      and/or enucleation was 68%. Three patients were treated with IAC as a salvage
      therapy, controlling the tumor in 2 patients at 6 months of follow-up. These are
      the first cases reported in Chile. Survival rate was 100%. CONCLUSION:
      Multidisciplinary management of retinoblastoma led to a survival rate and
      morbidity comparable with international reports.

PMID- 25617908
TI  - Identifying and intervening on barriers to healthcare access among members of a
      small Korean community in the southern USA.
AB  - OBJECTIVE: We used community-based participatory research (CBPR) to explore
      barriers to healthcare access and utilization and identify potentially effective
      intervention strategies to increase access among members of the Korean community
      in North Carolina (NC). METHODS: Our CBPR partnership conducted 8 focus groups
      with 63 adult Korean immigrants in northwest NC and 15 individual in-depth
      interviews and conducted an empowerment-based community forum. RESULTS: We
      identified 20 themes that we organized into four domains, including practical
      barriers to health care, negative perceptions about care, contingencies for care,
      and provider misconceptions about local needs. Forum attendees identified four
      strategies to improve Korean community health. CONCLUSION: Despite the
      implementation of the Patient Protection and Affordable Care Act (ACA), many
      Korean community members will continue to remain uninsured, and among those who
      obtain insurance, many barriers will remain. It is imperative to ensure the
      health of this highly neglected and vulnerable community. PRACTICE IMPLICATIONS:
      Potential strategies include the development of (1) low-literacy materials to
      educate members of the Korean community about how to access healthcare services,
      (2) lay health advisor programs to support navigation of service access and
      utilization, (3) church-based programming, and (4) provider education to reduce
      misconceptions about Korean community needs.

PMID- 25617907
TI  - Provider communication quality: influence of patients' weight and race.
AB  - OBJECTIVE: To examine the relationship between patient weight and provider
      communication quality and determine whether patient race/ethnicity modifies this
      association. METHODS: We conducted a cross-sectional analysis with 2009-2010
      medical expenditures panel survey-household component (N=25,971). Our dependent
      variables were patient report of providers explaining well, listening, showing
      respect, and spending time. Our independent variables were patient weight status
      and patient weight-race/ethnicity groups. Using survey weights, we performed
      multivariate logistic regression to examine the adjusted association between
      patient weight and patient-provider communication measures, and whether patient
      race/ethnicity modifies this relationship. RESULTS: Compared to healthy weight
      whites, obese blacks were less likely to report that their providers explained
      things well (OR 0.78; p=0.02) or spent enough time with them (OR 0.81; p=0.04),
      and overweight blacks were also less likely to report that providers spent enough
      time with them (OR 0.78; p=0.02). Healthy weight Hispanics were also less likely
      to report adequate provider explanations (OR 0.74; p=0.04). CONCLUSION: Our study
      provides preliminary evidence that overweight/obese black and healthy weight
      Hispanic patients experience disparities in provider communication quality.
      PRACTICE IMPLICATION: Curricula on weight bias and cultural competency might
      improve communication between providers and their overweight/obese black and
      healthy weight Hispanic patients.

PMID- 25617909
TI  - Quality of survival assessment in European childhood brain tumour trials, for
      children aged 5 years and over.
AB  - INTRODUCTION: There is increasing recognition of the long-term sequelae of brain
      tumours treated in childhood. Five year survival rates now exceed 75% and
      assessing the quality of survival (QoS) in multiple domains is essential to any
      comparison of the benefits and harms of treatment regimens. AIM: The aim of this
      position statement is to rationalise assessments and facilitate collection of a
      common data set across Europe. Sufficient numbers of observations can then be
      made to enable reliable comparisons between outcomes following different tumour
      types and treatments. METHODS: This paper represents the consensus view of the
      QoS working group of the Brain Tumour group of the European Society of Paediatric
      Oncology regarding domains of QoS to prioritise for assessment in clinical
      trials. This consensus between clinicians and researchers across Europe has been
      arrived at by discussion and collaboration over the last eight years. RESULTS:
      Areas of assessment discussed include core medical domains (e.g. vision, hearing,
      mobility, endocrine), emotion, behaviour, adaptive behaviour and cognitive
      functioning. CONCLUSIONS: A 'core plus' approach is suggested in which core
      assessments (both direct and indirect tests) are recommended for all clinical
      trials. The core component is a relatively brief screening assessment that, in
      most countries, is a sub-component of routine clinical provision. The 'plus'
      components enable the addition of assessments which can be selected by individual
      countries and/or tumour-, age-, and location-specific groups. The implementation
      of a QoS protocol common to all European clinical studies of childhood brain
      tumours is also discussed.

PMID- 25617910
TI  - Neuropsychological short assessment of disease- and treatment-related
      intelligence deficits in children with brain tumours.
AB  - OBJECTIVE: The Wuerzburger Psychologische Kurz-Diagnostik (WUEP-KD) is a short
      screening battery for cognitive deficits in children with brain tumour. We report
      on its psychometric quality and testing efficiency. MATERIAL AND METHODS: WUEP-KD
      was founded on Cattell-Horn-Carroll (CHC) framework of cognitive abilities. We
      assessed the construct validity of the short battery by conducting factor
      analysis and the concurrent validity by multiple linear regressions with Kaufman
      Assessment Battery for Children (K-ABC). The concurrent validity was explored by
      multiple linear regressions with Wechsler Intelligence Scale for Children (WISC).
      The discriminant validity was examined by a reanalysis of harmful effects of
      brain tumour treatments in a medulloblastoma cohort. RESULTS: The construct
      validity assessment revealed three neuropsychological domains: cognitive
      operations, executive abilities, and psychomotor abilities. The retest
      reliabilities for individual testing and the convergent coefficients of the WUEP
      KD with K-ABC and WISC yielded satisfactory results. The cognitive effects of
      different treatment modalities in the medulloblastoma cohort matched exactly
      previously reported data on the decline of general intelligence scores and
      delivered the details for the harmful effects. An in-depth analysis based on
      Hedges' g effect sizes confirmed specific harmful late effects on all abilities
      of cognitive operations, on the executive ability of perceptual speed and on
      psychomotor ability of movement steadiness. CONCLUSION: WUEP-KD is a valid and
      efficient short test instrument, which may be especially useful in larger
      cohorts, multicenter settings or if patients do not tolerate longer tests. Due to
      its foundation on the CHC framework, our findings provide a rationale to create a
      common data set along with scores from other factor-based tests in international
      studies.

PMID- 25617911
TI  - [Geriatric medicine at the undergraduate level: students and elderly people they
      deserve it].

PMID- 25617912
TI  - Comparative study of living and deceased donor liver transplantation as a
      treatment for hepatocellular carcinoma.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) is an important treatment
      option for unresectable hepatocellular carcinoma (HCC), but whether recurrence
      and survival in LDLT differ from those in deceased donor liver transplantation
      (DDLT) remains controversial. STUDY DESIGN: A retrospective analysis was
      performed between patients with HCC who underwent LDLT in a Japanese institute (n
      = 133) and those who underwent DDLT in a United States institute (n = 362).
      RESULTS: Although there was a difference in patient background characteristics
      (eg, body mass index, donor age, Model for End-Stage Liver Disease [MELD] score),
      tumor aggressiveness represented by Milan criteria and microscopic vascular
      invasion were comparable between the 2 groups. The cumulative 5-year recurrence
      rates of the LDLT group and the DDLT group were similar (14.8% vs 19.0%, p =
      0.638), but overall survival in the LDLT group was significantly better than that
      in the DDLT group (84.2% vs 63.5%, p < 0.0001). Separate multivariate analysis
      identified different preoperative predictive factors for HCC recurrence (salvage
      transplantation and Des-gamma-carboxy prothrombin >300 in the LDLT group, beyond
      Milan criteria in the DDLT group). Combined multivariate analysis of the 2 groups
      identified recipient's body mass image >30 kg/m(2) as an independent risk factor
      for overall survival; the technique of transplantation (LDLT or DDLT) was not
      found to be a risk factor. CONCLUSIONS: When compared between the institutes
      where LDLT or DDLT were the first treatment choices for unresectable HCC,
      recurrence rates were comparable. Living donor liver trasplantation is a viable
      treatment option for unresectable HCC, providing recurrence rates similar to
      those achieved with DDLT.

PMID- 25617913
TI  - Chemotherapy-induced splenic volume increase is independently associated with
      major complications after hepatic resection for metastatic colorectal cancer.
AB  - BACKGROUND: In patients with colorectal cancer liver metastases (CRCLM),
      chemotherapy-induced hepatic injury is associated with increased splenic volume,
      thrombocytopenia, and decreased long-term survival. The current study
      investigates the relationship between change in splenic volume after preoperative
      chemotherapy and development of postoperative complications. STUDY DESIGN: The
      study group consisted of 80 patients who underwent resection of CRCLM; half
      received neoadjuvant chemotherapy for 6 months before resection (n = 40) and the
      other half did not (n = 40). The study group was compared with two control
      groups: a normal group composed of patients undergoing cholecystectomy for benign
      disease (n = 40) and a group of untreated, nonmetastatic colorectal cancer (CRC)
      patients (n = 40). Splenic volume was measured by CT/MRI volumetry. In the study
      group, the nontumoral liver was graded for steatosis and sinusoidal injury;
      operative and outcomes characteristics were also analyzed. RESULTS: Before
      chemotherapy, CRCLM patients had normalized spleen volumes of 3.2 +/- 1.1 mL/kg,
      significantly higher than normal (2.5 +/- 0.8 mL/kg; p < 0.001) and nonmetastatic
      CRC (2.6 +/- 1.3 mL/kg; p < 0.05) patients, with higher splenic volume after 6
      months of chemotherapy (4.2 +/- 1.7 mL/kg; p < 0.01). After chemotherapy, splenic
      volume increase was associated with any perioperative complication (p < 0.01) and
      major complications (p < 0.05). Patients with >=39% splenic volume increase
      (maximal chi-square test) were significantly more likely to have major
      complications (p < 0.01). Spleen volume changes were not correlated with change
      in platelet count (R(2) = 0.03; p = 0.301). CONCLUSIONS: In patients with CRCLM,
      the presence of liver metastases and chemotherapy are associated with higher
      splenic volume. Percent splenic volume increase after 6 months of chemotherapy
      can aid preoperative risk stratification, as it was an independent predictor of
      major postoperative complications.

PMID- 25617914
TI  - Use of the American College of Surgeons NSQIP Surgical Risk Calculator for
      Laparoscopic Colectomy: how good is it and how can we improve it?
AB  - BACKGROUND: The American College of Surgeons NSQIP risk calculator was developed
      from multi-institutional clinical data to estimate preoperative risk. The impact
      of outliers has the potential to greatly affect predictions. Although the effect
      of outliers is minimized in large series, their impact on the individual provider
      or institution could be profound. No previous study has assessed the risk
      calculator for a single institution or provider, including outliers. Our goal was
      to evaluate the accuracy of the predicted outcomes at a single institution. STUDY
      DESIGN: Laparoscopic colectomies performed by two colorectal surgeons at a
      tertiary referral center were prospectively evaluated using the risk calculator.
      Predicted outcomes were compared with actual outcomes for length of stay (LOS),
      complications, return to the operating room, and death. Main outcomes measures
      were differences in actual vs predicted outcomes. RESULTS: One hundred and
      sixteen patients were included. Actual LOS was higher than predicted (mean +/- SD
      4.22 +/- 5.49 days vs predicted 4.11 +/- 1.18 days; p = 0.0001). Four outliers
      with multiple complications had an LOS >3 SDs from the mean. After removing
      these, observed LOS was significantly shorter than predicted (adjusted LOS mean
      +/- SD 3.31 +/- 2.30 days vs predicted 4.05 +/- 1.14 days; p = 0.002). Occurrence
      of any complication was significantly lower than predicted (17.3% vs 19.4%; p =
      0.05). Rates of major complications (13.2% vs 19.4%; p = 0.009) and surgical site
      infections (9.8% vs 11.8%; p = 0.006) were also significantly lower than
      predicted. There were no significant differences in death, urinary tract
      infection, renal failure, and reoperation rates. CONCLUSIONS: Although the risk
      calculator was effective for evaluating average surgical-risk patients, it does
      not accurately predict outcomes in a small percentage of patients when one or
      more serious complications occur. Addition of surgeon- and patient-specific data
      via the American College of Surgeons case-logging system could better adjust for
      these areas.

PMID- 25617916
TI  - Was the French clinical surveillance system of bovine brucellosis influenced by
      the occurrence and surveillance of other abortive diseases?
AB  - The bovine brucellosis clinical surveillance system implemented in France aims to
      detect early any case of bovine brucellosis, a disease of which the country has
      been declared free since 2005. It relies on the mandatory notification of every
      bovine abortion. Following the spread of the Schmallenberg virus (SBV) in France
      in 2012 and 2013, and the implementation in 2012 of a clinical surveillance
      programme of Q fever based on abortion notifications in ten pilot departements,
      our objective was to study whether these two events influenced the brucellosis
      clinical surveillance system. The proportion of notifying farmers was analyzed
      over each semester from June 1, 2009 to June 30, 2013 according to the size and
      production type of herds, SBV status of departements and the implementation of
      the Q fever surveillance. Our analysis showed a slight increase in the proportion
      of notifying farmers as departements became infected by SBV, and after the
      implementation of Q fever surveillance (during the first semester of 2013). These
      variations might be explained by an increase in abortion occurrence (congenital
      deformities in newborns, due to SBV) and/or by an increase in farmers' and
      veterinarians' awareness (due to the spread of SBV and the implementation of the
      Q fever surveillance). These results highlight the difficulties in interpreting
      variations in the proportion of notifying farmers as a consequence of an increase
      in abortion occurrence. As bovine abortion surveillance can play an important
      role in the early warning for several diseases, there is a need to explore other
      ways to monitor abortions in cattle, such as syndromic surveillance using the
      dates of artificial insemination or calving data. 

PMID- 25617917
TI  - [The strength of endocrinology 2014].

PMID- 25617918
TI  - [Therapeutic issues concerning male fertility].
AB  - Men reproductive health has long been ignored although it is responsible for 50%
      of couple's infertility. However, in recent years, the understanding of endocrine
      physiology underlying testis development and spermatogenesis has enabled the
      development of new therapeutic strategies. Some concern the management of male
      infertility. Others are dealing with finding an effective male contraceptive. In
      this review, we first present the management of infertility, in patients with
      congenital hypogonadotropic hypogonadism. We then describe the major improvements
      for Klinefelter patient's infertility. Finally, we review the different hormonal
      and non-hormonal methods for male contraception, currently in development.
      Efficacy and safety of the some non-hormonal methods remain to be demonstrated so
      far in humans. 

PMID- 25617915
TI  - Self-expanding covered metallic stent as a bridge to surgery in esophageal
      cancer: impact on oncologic outcomes.
AB  - BACKGROUND: Self-expanding metallic stents (SEMSs) have been used as a bridge to
      surgery, relieving dysphagia and maintaining nutrition, in patients with operable
      but obstructive esophageal cancer (EC). However, the impact of SEMSs on oncologic
      outcomes is unknown. The aim of this study was to evaluate the impact of SEMS
      insertion before EC surgery on oncologic outcomes. STUDY DESIGN: From 2000 to
      2010, two thousand nine hundred and forty-four patients who underwent an
      operation for EC with a curative intent were included in a multicenter European
      cohort. Through propensity score analysis, patients who underwent SEMS insertion
      (SEMS group, n = 38) were matched 1:4 to control patients who did not undergo
      SEMS insertion (control group, n = 152). RESULTS: The SEMS and control groups
      were comparable according to age, sex, tumor location, clinical stage, American
      Society of Anesthesiologists score, dysphagia, malnutrition, neoadjuvant
      treatment administration, histology, and surgical procedure. Self-expanding
      metallic stent insertion was complicated by tumoral perforation in 2 patients.
      The in-hospital postoperative mortality and morbidity rates for the SEMS vs
      control groups were 13.2% vs 8.6% (p = 0.370) and 63.2% vs 59.2% (p = 0.658),
      respectively. The R0 resection rate (71.0% vs 85.5%; p = 0.041), median time to
      recurrence (6.5 vs 9.0 months; p = 0.040), and 3-year overall survival (25% vs
      44%; p = 0.023) were significantly reduced in the SEMS group, and the 3-year
      locoregional recurrence rate was increased (62% vs 34%; p = 0.049). The results
      remained significant after excluding SEMS-related esophageal perforations. After
      adjusting for confounding factors, SEMS insertion was a predictor of poor
      prognosis (hazard ratio = 1.6; p = 0.038). CONCLUSIONS: Self-expanding metallic
      stent insertion, as a bridge to surgery, has a negative impact on oncologic
      outcomes in EC. Clinicaltrials.gov ID: NCT 01927016.

PMID- 25617919
TI  - [What's new in follicular thyroid cancer management in 2014?].
AB  - The American Thyroid Association has presented new guidelines for the management
      of thyroid cancer. These guidelines tend to appreciate more accurately the
      individual risk of patients, to adapt accordingly the treatment and the follow
      up. The initial risk stratification has been completed, especially precising the
      risk of N1 patients, follicular thyroid cancers, and the prognostic impact of
      molecular markers. Indications, doses and modalities of radioiodine (RAI) have
      been reevaluated, restricting its utilization in order to avoid overtreatment of
      low risk patients. Moreover the response to initial treatment allows to
      restratify the risk of the patients, and to adapt the monitoring and the thyroid
      hormone therapy management. The risk of suppressive thyroid hormone therapy has
      also to be considered. Concerning advanced thyroid cancer, prognosis is mainly
      depending on its RAI sensitivity. The systemic treatment of progressive,
      threatening refractory cancers is nowadays based on targeted therapy. However
      none of these treatments has demonstrated an improvement in overall survival, and
      side effects are frequent. Fagin et al presented promising results concerning
      short term treatment with selective inhibitors of the MAPK pathway, able to
      partially restore RAI sensitivity of refractory lesions in murine models, and
      recently in human patients. 

PMID- 25617920
TI  - [Primary hyperparathyroidism: new concepts, new recommendations].
AB  - Today, primary hyperparathyroidism (PHPT) is frequently diagnosed at an
      asymptomatic stage. New international guidelines presented at the Endocrine
      Society congress update the management of this disease. Normocalcemic PHPT is
      part of the diagnostic spectrum of PHPT, its natural history is poorly known, and
      monitoring is proposed once secondary HPT has been eliminated. Bone involvement,
      classically predominant in cortical bone, also affects trabecular bone.
      Osteodensitometry is poorly effective at the vertebral level and new methods
      (trabecular bone score [TBS], vertebral fracture assessment [VFA]) should improve
      the assessment of the risk of fracture. The kidney is the most frequently
      symptomatic organ, and an imaging workup as well as urinary tests are recommended
      in all patients when searching for causes of lithiasis or nephrocalcinosis. More
      than 10% of PHPT cases are related to a germinal mutation: these patients should
      be identified to optimize their management and that of their relatives. Medical
      treatment is reserved for patients for whom surgery is not indicated or possible:
      cinacalcet is effective for calcemia, the bisphosphonates are effective for bone
      involvement. Vitamin D deficiency can be corrected as long as calcemia and
      creatinuria are monitored. Surgical treatment is recommended in case of
      pronounced hypercalcemia, bone or renal involvement, and age less than 50 years
      and in patients in whom monitoring is refused or impossible. Studies have shown
      that asymptomatic PHPT evolves little in monitored patients. 

PMID- 25617921
TI  - [New insights in adrenal Cushing syndrome].
AB  - The development of molecular biology tools has allowed major advances in the
      genetic determinism and the pathophysiology of pheochromocytomas and Conn's
      adenomas. However, the molecular pathophysiology of ACTH-independent Cushing's
      Syndrome was mostly unknown until recently. In 2014, major new insights
      concerning the physiopathology of ACTH-independent macronodular adrenal
      hyperplasias (AIMAH) and the cortisol-secreting adenomas have been published.
      Elsewhere, the cardiovascular consequences of the subclinical hypercortisolism
      due to adrenal incidentalomas, was described only in some cross-sectional
      studies. The natural history of these lesions has been documented in two large
      follow-up studies. These new data presented during the Endocrine Congress are
      summarized herein. 

PMID- 25617922
TI  - [Craniopharyngiomas: progress in pathogenesis and therapeutics].
AB  - This review focuses on new aspects in craniopharyngiomas with emphasis on
      pathogenic mechanisms and treatment strategies that were presented at the joined
      Endocrine Society/International Society of Endocrinology meeting in Chicago in
      June 2014. Craniopharyngiomas are benign epithelial tumors arising from the
      pituitary stalk or gland. Two subtypes could be distinguished: an adamatinomatous
      form that is more common in children, and a papillary form that is observed
      almost exclusively in adults. Besides these histological differences, these two
      variants differ in some molecular features that have been recently identified and
      could have important therapeutic implications. Despite its histologically benign
      nature, the morbidities related to the tumor itself or its treatment raise many
      concerns and excess mortality rates up to nine times higher than in the general
      population has been reported. Among the potential sequelae of craniopharyngiomas,
      obesity seems the most frequent. The difficulty in the management of this obesity
      lies in its complex underlying pathophysiological mechanisms. Complete resection
      of localized tumors should be attempted while a limited hypothalamus-sparing
      surgery followed or not by radiotherapy should be adopted in tumors involving the
      hypothalamus. A multidisciplinary approach including, in particular, a dedicated
      neurosurgeon, and a therapeutic strategy tailored to the individual presentation
      of the craniopharyngioma in any patient should be initiated at diagnosis for
      improving the prognosis of these tumors. 

PMID- 25617923
TI  - The big data revolution: from drug development to better health outcomes?

PMID- 25617924
TI  - Medicaid expansion choices mean different care for poor diabetics, depending on
      where they live.

PMID- 25617926
TI  - Stem cells create a therapeutic niche.

PMID- 25617925
TI  - The Yin and the Yang of CV risks in patients with diabetes.

PMID- 25617927
TI  - Cleveland clinic study: use of bariatric surgery beats medical therapy in
      diabetes management.

PMID- 25617928
TI  - Diet drinks linked to heart trouble for older women.

PMID- 25617929
TI  - Aims of ACA get better reviews than implementation at cardiologists' meeting.

PMID- 25617930
TI  - To treat or not to treat? Questions, controversies in prevention.

PMID- 25617931
TI  - Use of rivaroxaban could trim hospital spending in treating pulmonary embolism.

PMID- 25617932
TI  - Relationship between cardiac issues, diabetes gets plenty of attention.

PMID- 25617933
TI  - Study answers long-standing question about metformin after heart attack.

PMID- 25617934
TI  - The persistent complication of hypoglycemia in diabetics.

PMID- 25617935
TI  - Inhaled insulin's long journey to commercialization.

PMID- 25617936
TI  - A patient's opinion of unmet need.

PMID- 25617937
TI  - The role of bioinformatics in diabetes drug development--and precision medicine.

PMID- 25617938
TI  - The how and why of stress, diabetes, and the brain.

PMID- 25617939
TI  - Evidence builds on yoga, but no reimbursement yet.

PMID- 25617941
TI  - Two degree of freedom control scheme for unstable processes with small time
      delay.
AB  - In this work, a recently reported two degree of freedom control structure namely
      the Parallel Control Structure (PCS) is modified to achieve improved control
      performance for unstable processes. New tuning rules are proposed using a direct
      synthesis approach for unstable first order plus time delay (UFOPTD), unstable
      second order plus time delay (USOPTD) and integrating and unstable plus time
      delay (IUPTD) process models. The proposed method has two tuning parameters whose
      suitable values are recommended after studying their effect on the system
      performance and robustness. This is an advantage of the present work over the
      other reported control schemes where the authors provide suitable ranges of the
      tuning parameters values. Simulation examples show that the present scheme
      results in improved nominal and perturbed responses as compared to the recently
      reported methods. Also it is observed that satisfactory performance is achieved
      when the proposed tuning rules are applied on an isothermal chemical reactor
      which exhibits multiple steady state solutions. 

PMID- 25617940
TI  - Association of morphologic characteristics on optical coherence tomography and
      angiographic progression patterns of late restenosis after drug-eluting stent
      implantation.
AB  - OBJECTIVES: To gain insight into the pathophysiology of late drug-eluting stent
      (DES) restenosis. BACKGROUND: Restenosis of DES has a different time course from
      that of bare metal stents. METHODS: Patients who underwent follow-up coronary
      angiography (CAG) twice (six to nine months and 18 to 24 months) after DES
      implantation were examined using optical coherence tomography (OCT). All lesions
      with target lesion revascularization at first follow-up were excluded. Late catch
      up was defined as lesions that progressed from less than 50% diameter stenosis
      (DS) at the first CAG to more than 50% DS at the second CAG. Lesions with the
      late catch-up were further divided into two groups; lesions with jump-up (less
      than 25% DS at the first CAG) and lesions with gradual progression (25-50% DS at
      the first CAG). RESULTS: Of the 25 patients who had late ISR, 23 patients (10
      jump-up/13 gradual progression) were examined with OCT at late follow-up and
      enrolled in this study. In the qualitative OCT assessment, each ratio of
      homogeneous, layered, heterogeneous with or without attenuation tissue
      morphologies were in jump-up group, and gradual progression group were 0% and
      15%, 0% and 23%, and 60% and 8%, and 40% and 54%, respectively. All of jump-up
      group showed heterogeneous restenotic tissue, while 62% of gradual progression
      group showed heterogeneous restenotic tissue (P = .04). CONCLUSIONS: These
      findings suggest different pathophysiology of the late catch-up after DES
      implantation between the jump-up and gradual progression groups.

PMID- 25617942
TI  - Stability analysis of a class of fractional order nonlinear systems with order
      lying in (0, 2).
AB  - This paper investigates the stability of n-dimensional fractional order nonlinear
      systems with commensurate order 0 <alpha<2. By using the Mittag-Leffler function,
      Laplace transform and the Gronwall-Bellman lemma, one sufficient condition is
      attained for the local asymptotical stability of a class of fractional order
      nonlinear systems with order lying in (0, 2). According to this theory,
      stabilizing a class of fractional order nonlinear systems only need a linear
      state feedback controller. Simulation results demonstrate the effectiveness of
      the proposed theory. 

PMID- 25617943
TI  - A message from the editor - January 2015.

PMID- 25617944
TI  - Evaluating the effect of Japan's 2004 postgraduate training programme on the
      spatial distribution of physicians.
AB  - BACKGROUND: In 2004, the Japanese government permitted medical graduates for the
      first time to choose their training location directly through a national matching
      system. While the reform has had a major impact on physicians' placement,
      research on the impact of the new system on physician distribution in Japan has
      been limited. In this study, we sought to examine the determinants of physicians'
      practice location choice, as well as factors influencing their geographic
      distribution before and after the launch of Japan's 2004 postgraduate medical
      training programme. METHODS: We analyzed secondary data. The dependent variable
      was the change in physician supply at the secondary tier of medical care in
      Japan, a level which is roughly comparable to a Hospital Service Area in the US.
      Physicians were categorized into two groups according to the institutions where
      they practiced; specifically, hospitals and clinics. We considered the following
      predictors of physician supply: ratio of physicians per 1,000 population
      (physician density), age-adjusted mortality, as well as measures of residential
      quality. Ordinary least-squares regression models were used to estimate the
      associations. A coefficient equality test was performed to examine differences in
      predictors before and after 2004. RESULTS: Baseline physician density showed a
      positive association with the change in physician supply after the launch of the
      2004 programme (P-value < .001), whereas no such effect was found before 2004.
      Urban locations were inversely associated with the change in physician supply
      before 2004 (P-value = .026), whereas a positive association was found after 2004
      (P-value < .001). Urban location and area-level socioeconomic status were
      positively correlated with the change in hospital physician supply after 2004 (P
      values < .001 for urban centre, and .025 for area-level socioeconomic status),
      even though in the period prior to the 2004 training scheme, urban location was
      inversely associated with the change in physician supply (P-value = .015) and
      area-level socioeconomic status was not correlated. CONCLUSION: Following the
      introduction of the 2004 postgraduate training programme, physicians in Japan
      were more likely to move to areas with already high physician density and urban
      locations. These changes worsened regional inequality in physician supply,
      particularly hospital doctors.

PMID- 25617945
TI  - Nobody's children.

PMID- 25617946
TI  - I'll have what they're having.

PMID- 25617947
TI  - The frontline of the infectious diseases and diabetes battle.

PMID- 25617948
TI  - Body language.

PMID- 25617949
TI  - New traditions in Middle Eastern hospitality.

PMID- 25617950
TI  - Value of gadoxetic acid-enhanced and diffusion-weighted MR imaging in evaluation
      of hepatocellular carcinomas with atypical enhancement pattern on contrast
      enhanced multiphasic MDCT in patients with chronic liver disease.
AB  - OBJECTIVE: The purpose of this study was to investigate the value of enhancement
      kinetics and ancillary imaging findings on gadoxetic acid-enhanced and diffusion
      weighted (DW) MR imaging for diagnosing hepatocellular carcinomas (HCCs) without
      the typical enhancement pattern on contrast-enhanced multiphasic MDCT in patients
      with chronic liver disease. MATERIALS AND METHODS: Eighty-two surgically
      confirmed HCCs without the typical enhancement pattern (hypervascular in the
      arterial phase, followed by washout on the portal or equilibrium phases) on
      triple-phase MDCT were enrolled in this study. The patients were classified into
      four categories based on the CT density pattern of arterial and equilibrium
      phases (isodense-isodense, hypodense-hypodense, isodense-hypodense, and
      hyperdense-isodense) compared to liver parenchyma. Signal intensity of HCCs on T2
      weighted images (T2WI), arterial phase, 3 min late-phase, hepatobiliary phase
      (HBP) and DW images with a b value of 800 s/mm2 were qualitatively evaluated, and
      ADC values were measured. Fisher's exact test and Chi-square test were used to
      compare the frequency and trend of hyperintensity on T2WI, hypointensity on HBP
      images, hyperintensity on DW images, and histopathologic grades between groups
      with different CT density patterns. Kruskal-Wallis test was used to compare the
      ADC value between groups. RESULTS: Thirty and 52 HCCs were categorized as
      hypervascular (hyperdense-isodense) and non-hypervascular HCCs (3, isodense
      isodense; 37, hypodense-hypodense; 12, isodense-hypodense), respectively. Most
      HCCs showed hyperintensity on T2WI (77/82, 93.9%) and DW images (81/82, 98.8%)
      and hypointensity on HBP images (80/82, 97.6%). Thirty-eight HCCs (38/82, 46.3%)
      showed typical HCC enhancement pattern on dynamic MR images. There were no
      significant differences in the frequency and trend of signal intensity on T2WI,
      HBP images, DW images, and histopathologic grades with regard to the four CT
      density patterns (p<0.05). No significant difference in mean ADC values between
      groups was identified (p<0.05). CONCLUSION: Gadoxetic acid-enhanced and DW MR
      imaging can help diagnose HCCs with atypical enhancement patterns on multiphasic
      CT in patients with chronic liver disease.

PMID- 25617951
TI  - Ultrasound-guided injection into the lower joint space of the temporomandibular
      joint.
AB  - A procedure for ultrasound-guided injection into the lower joint space of the
      temporomandibular joint is presented. 

PMID- 25617952
TI  - Heterotopic bone formation in the musculus latissimus dorsi of sheep using beta
      tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on
      bone formation and matrix degeneration.
AB  - We previously generated viable heterotopic bone in living animals and found that
      3 months of intrinsic vascularization improved bone formation and matrix
      degeneration. In this study, we varied the pre-vascularization time to determine
      its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm
      long cylindrical beta-tricalcium phosphate scaffolds were filled intraoperatively
      with autogenous iliac crest bone marrow and implanted in the latissimus dorsi
      muscle in six sheep. To examine the effect of axial perfusion, one scaffold was
      surgically implanted with (group C) or without (group D) a central vascular
      bundle. All animals were sacrificed 6 months postoperatively and
      histomorphometric measurements were compared to previous results. All implanted
      scaffolds exhibited ectopic bone growth. However, bone growth was not
      significantly different between the 3-month (group A, 0.191+/-0.097 vs. group C,
      0.237+/-0.075; P=0.345) and 6-month (group B, 0.303+/-0.105 vs. group D, 0.365+/
      0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early
      differences between surgically and extrinsically vascularized constructs
      disappeared after 6 months. Here, we describe a reliable procedure for generating
      ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient
      and ceramic degradation proceeds in accordance with bone generation, supporting
      the hypothesis of cell-mediated resorption.

PMID- 25617953
TI  - Visfatin reduces hippocampal CA1 cells death and improves learning and memory
      deficits after transient global ischemia/reperfusion.
AB  - Visfatin is a novel adipocytokine with insulin-mimetic effect which plays a role
      in glucose-lowering effect of insulin and improves insulin sensitivity. It has
      been linked to a variety of cellular processes and its plays important roles in
      cell apoptosis and survival. Moreover, cerebral ischemia causes loss of
      hippocampus pyramidal cells, therefore, in this study; we investigated the
      neuroprotective effect of visfatin after global cerebral ischemia in male rats.
      Both common carotid arteries were occluded for 20 minutes followed by 4 days of
      reperfusion. Animals were treated with either the Visfatin (intracerebro
      ventricular; 100 ng) or saline vehicle (2 ul) at the time of reperfusion.
      Behavioral examination, apoptosis and necrosis assessment were performed 4 days
      after ischemia. Visfatin significantly reduced Caspase-3 activation (P < 0.001),
      TUNEL positive cells (P < 0.05) and necrotic cell death in the CA1 region of the
      hippocampus (P < 0.001). Moreover, treatment with visfatin significantly improved
      memory deficits of cerebral ischemia-reperfusion rats (P < 0.05). The results
      suggest that visfatin via its antiapoptotic properties has significant
      neuroprotective effects on cerebral ischemia reperfusion injury in rats.

PMID- 25617954
TI  - Biomechanical evaluation of 4-strand flexor tendon repair techniques, including a
      combined Kessler-Tsuge approach.
AB  - PURPOSE: To test the ultimate tensile strength and stiffness of 3 flexor tendon
      repair techniques using looped suture material. METHODS: Seventeen fresh porcine
      flexor tendons were randomized to a single-throw, 4-strand Kessler technique with
      a looped structure, a double-throw, 4-strand Tsuge technique with 2 looped
      structures, or a single-throw, 4-strand Kessler-Tsuge technique with a looped
      structure. Thirty additional fresh porcine flexor tendons were randomized to the
      same techniques but with a running epitendinous repair. We measured ultimate
      tensile strength to failure and stiffness and recorded the cause of failure.
      RESULTS: The Tsuge technique had the highest mean ultimate tensile strength at 75
      N (SD, 14 N) versus 63 N (SD, 13 N) for the Kessler-Tsuge method and 46 N (SD, 11
      N) for the Kessler technique. Differences between the Tsuge and Kessler-Tsuge,
      the Kessler-Tsuge and Kessler, and the Tsuge and Kessler techniques were
      significant. Mean suture stiffness was 6.8 N/mm for the Tsuge technique, 5.7 N/mm
      for the Kessler-Tsuge technique, and 4.6 N/mm for the Kessler technique. The
      difference between the Tsuge and Kessler techniques was significant. Analyzing
      the tests with or without an epitendinous suture separately did not affect the
      significance of the differences. CONCLUSIONS: The modified double-throw, 4-strand
      Tsuge was the strongest suture technique in this study. It may be a clinically
      acceptable, albeit slightly weaker alternative to the more complicated Tsuge
      method. CLINICAL RELEVANCE: A combined Kessler-Tsuge approach might be an option
      for flexor tendon repair.

PMID- 25617955
TI  - Functionality after arthroscopic debridement of central triangular fibrocartilage
      tears with central perforations.
AB  - PURPOSE: To investigate functional and subjective outcome parameters after
      arthroscopic debridement of central articular disc lesions (Palmer type 2C) and
      to correlate these findings with ulna length. METHODS: Fifty patients (15 men; 35
      women; mean age, 47 y) with Palmer type 2C lesions underwent arthroscopic
      debridement. Nine of these patients (3 men; 6 women; mean static ulnar variance,
      2.4 mm; SD, 0.5 mm) later underwent ulnar shortening osteotomy because of
      persistent pain and had a mean follow-up of 36 months. Mean follow-up was 38
      months for patients with debridement only (mean static ulnar variance, 0.5 mm;
      SD, 1.2 mm). Examination parameters included range of motion, grip and pinch
      strengths, pain (visual analog scale), and functional outcome scores (Modified
      Mayo Wrist score [MMWS] and Disabilities of the Arm, Shoulder, and Hand [DASH]
      questionnaire). RESULTS: Patients who had debridement only reached a DASH
      questionnaire score of 18 and an MMWS of 89 with significant pain reduction from
      7.6 to 2.0 on the visual analog scale. Patients with additional ulnar shortening
      reached a DASH questionnaire score of 18 and an MMWS of 88, with significant pain
      reduction from 7.4 to 2.5. Neither surgical treatment compromised grip and pinch
      strength in comparison with the contralateral side. We identified 1.8 mm or more
      of positive ulnar variance as an indication for early ulnar shortening in the
      case of persistent ulnar-sided wrist pain after arthroscopic debridement.
      CONCLUSIONS: Arthroscopic debridement was a sufficient and reliable treatment
      option for the majority of patients with Palmer type 2C lesions. Because reliable
      predictors of the necessity for ulnar shortening are lacking, we recommend
      arthroscopic debridement as a first-line treatment for all triangular
      fibrocartilage 2C lesions, and, in the presence of persistent ulnar-sided wrist
      pain, ulnar shortening osteotomy after an interval of 6 months. Ulnar shortening
      proved to be sufficient and safe for these patients. Patients with persistent
      ulnar-sided wrist pain after debridement who had preoperative static positive
      ulnar variance of 1.8 mm or more may be treated by ulnar shortening earlier in
      order to spare them prolonged symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 25617956
TI  - Transfer of the radial nerve branch to the extensor carpi radialis brevis to the
      anterior interosseous nerve to reconstruct thumb and finger flexion.
AB  - PURPOSE: To report our experiences reconstructing thumb and finger flexion in
      patients with extensive palsy of the upper limb by transferring the radial nerve
      branch to the extensor carpi radialis brevis (ECRB) to the anterior interosseous
      nerve (AIN). METHODS: Within 8 months after injury, 4 patients with either a
      combined high median/ulnar nerve palsy or C7-T1 brachial plexus root avulsion
      underwent surgical reconstruction for thumb and finger flexion. As part of the
      reconstructive procedure, the branch of the radial nerve to the ECRB was
      transferred to the AIN. RESULTS: At final evaluation, which averaged 13 months
      postoperatively, all patients had recovered full finger and thumb flexion,
      scoring M4 per Medical Research Council guidelines. Average grasp strength was 5
      kg, and pinch strength was 2 kg. Even in anesthetic fingers and with their eyes
      closed, patients could correctly identify passive extension of their distal
      interphalangeal joints. Wrist extension was preserved in all patients.
      CONCLUSIONS: In 4 patients, transfer of the branch of the radial nerve to the
      ECRB to the AIN predictably reconstructed thumb and finger flexion. Finger
      flexion also recovered in those fingers in which the flexor digitorum profundus
      was primarily innervated by the ulnar nerve. Despite extended sensory deficits,
      patients ultimately were able to use their hands regularly in daily life. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 25617957
TI  - Commentary on "biomechanical characteristics of hemi-hamate reconstruction versus
      volar plate arthroplasty in the treatment of dorsal fracture dislocations of the
      proximal interphalangeal joint".

PMID- 25617958
TI  - 2013-2014 sterling bunnell traveling fellowship report.
AB  - Since 1982, the American Society for Surgery of the Hand has sponsored a young
      member each year as its Bunnell Traveling Fellow. The Sterling Bunnell Traveling
      Fellowship enables young hand surgeons to foster national and international
      relationships that contribute to their pursuit of higher learning and advance the
      principles of scholarship by improving treatment of hand and upper extremity
      disorders. As the Sterling Bunnell Traveling Fellow for 2013 to 2014, I studied
      microvascular osteochondral reconstruction of the upper extremity. The year
      allowed me to pursue research abroad and participate in novel operations. These
      experiences have challenged how I approach common osteoarticular problems in hand
      surgery. Leaders in wrist surgery around the globe helped me reconsider the
      treatment of osteonecrotic, degenerative, and posttraumatic cartilage loss in
      radical new ways. 

PMID- 25617959
TI  - Nuts and bolts: dimensions of commonly utilized screws in upper extremity
      surgery.
AB  - A plethora of screw designs and sizes are available from multiple companies for
      use in upper extremity surgery. Knowing the dimensions of screws is critical in
      the treatment of bone of varying dimensions for fractures, osteotomies, or
      arthrodeses. Although many screws are named by their major thread diameter, this
      is not always true. Because of this confusing nomenclature and vast number of
      options, we sought to review the most commonly used screws and codify their
      dimensions into a readily available article and reference chart. This article
      highlights the basic dimensions of commonly used headless screws, stand-alone lag
      screws, non-locking and locking screws for plating, and biocomposite screws.
      Commonly described treatments using these screws include fixation of elbow,
      wrist, carpal, metacarpal, and phalangeal fractures and osteotomies, as well as
      arthrodeses of upper extremity joints. This article and its tables are by no
      means exhaustive of all commercially available implants. The focus is on the most
      commonly used implants in the United States as of 2014.

PMID- 25617960
TI  - Collagenase injections in patients on warfarin.

PMID- 25617961
TI  - Classification of congenital anomalies of the hand and upper limb.

PMID- 25617962
TI  - Clinical reports: the importance of reporting a surgeon's level of expertise.

PMID- 25617963
TI  - Prevalence of body dysmorphic disorder among Swedish women: a population-based
      study.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) is characterized by a highly
      distressing and impairing preoccupation with nonexistent or slight defects in
      appearance. Patients with BDD present to both psychiatric and non-psychiatric
      physicians. A few studies have assessed BDD prevalence in representative samples
      of the general population and have demonstrated that this disorder is relatively
      common. Our primary objective was to assess the prevalence of BDD in the Swedish
      population because no data are currently available. METHODS: In the current cross
      sectional study, 2891 randomly selected Swedish women aged 18-60 years
      participated. The occurrence of BDD was assessed using the Body Dysmorphic
      Disorder Questionnaire (BDDQ), which is a validated self-report measure derived
      from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria
      for BDD. In addition, symptoms of depression and anxiety were measured using the
      Hospital Anxiety and Depression Scale (HADS). RESULTS: The prevalence of BDD
      among Swedish women was 2.1%. The women with BDD had significantly more symptoms
      of depression and anxiety than the women without BDD. Depression (HADS depression
      score >= 8) and anxiety (HADS anxiety score >= 8) were reported by 42% and 72% of
      the women with BDD, respectively. CONCLUSIONS: The results of the present study
      indicate that BDD is relatively common among Swedish women (2.1%) and that it is
      associated with significant morbidity.

PMID- 25617964
TI  - Trajectories of medication attitudes and adherence behavior change in non
      adherent bipolar patients.
AB  - OBJECTIVES: While medication treatment is necessary for the successful management
      of bipolar disorder (BD), non-adherence rates are up to 60%. Although medication
      attitudes are believed to be relevant to adherence behavior, few studies have
      investigated the trajectories of adherence change. This study evaluated
      attitudinal correlates of adherence conversion in 86 poorly adherent individuals
      with BD. METHODS: This secondary analysis pooled data from two uncontrolled
      prospective trials of customized adherence enhancement (CAE), a psychosocial
      intervention delivered over 4-6 weeks. Poor adherence was defined as missing at
      least 20% of prescribed BD medication based on the self-reported Tablets Routine
      Questionnaire (TRQ). The sample was dichotomized into converters who achieved
      good adherence (N=44) and non-converters who remained poorly adherent (N=21).
      Converters vs. non-converters were compared on adherence, attitudes, and symptoms
      at baseline, 6 weeks and 3 months. RESULTS: At baseline, converters and non
      converters were similar demographically and clinically, but converters were less
      non-adherent (32% doses missed) than non-converters (59% missed). At 6 weeks,
      converters had better attitudes than non-converters. At 3 months, converters
      maintained improvements, but group differences were less pronounced due to some
      improvement in non-converters. Converters had better adherence at 3 months and
      trajectories differed for the groups on attitudes. Symptoms gradually improved
      for both converters and non-converters. CONCLUSIONS: Over two-thirds of poorly
      adherent BD patients who received CAE converted to good adherence. Improved
      medication attitudes may be a driver of improved adherence behavior and
      ultimately reduce BD symptoms.

PMID- 25617966
TI  - Improved transgene integration into the Chinese hamster ovary cell genome using
      the Cre-loxP system.
AB  - Genetic engineering of cellular genomes has provided useful tools for biomedical
      and pharmaceutical studies such as the generation of transgenic animals and
      producer cells of biopharmaceutical proteins. Gene integration using site
      specific recombinases enables precise transgene insertion into predetermined
      genomic sites if the target site sequence is introduced into a specific
      chromosomal locus. We previously developed an accumulative site-specific gene
      integration system (AGIS) using Cre and mutated loxPs. The system enabled the
      repeated integration of multiple transgenes into a predetermined locus of a
      genome. In this study, we explored applicable mutated loxP pairs for AGIS to
      improve the integration efficiency. The integration efficiencies of 52 mutated
      loxP sequences, including novel sequences, were measured using an in vitro
      evaluation system. Among mutated loxP pairs that exhibited a high integration
      efficiency, the applicability of the selected pairs to AGIS was confirmed for
      transgene integration into the Chinese hamster ovary cell genome. The newly found
      mutated loxP pairs should be useful for Cre-mediated integration of transgenes
      and AGIS.

PMID- 25617967
TI  - Ultrasonic cavitation erosion of high-velocity oxygen-fuel (HVOF) sprayed near
      nanostructured WC-10Co-4Cr coating in NaCl solution.
AB  - The high-velocity oxygen-fuel (HVOF) spraying process was used to prepare near
      nanostructured WC-10Co-4Cr coating. The cavitation erosion behavior and mechanism
      of the coating in 3.5 wt.% NaCl solution were analyzed in detail. The results
      showed that the amorphous phase and WC grain were present in the coating. The
      cavitation erosion resistance of the coating was about 1.27 times that of the
      stainless steel 1Cr18Ni9Ti under the same testing conditions. The effects of
      erosion time on the microstructural evolution were discussed. It was revealed
      that cracks initiated at the edge of pre-existing pores and propagated along the
      carbide-binder interface, leading to the pull-out of carbide particle and the
      formation of pits and craters on the surface. The main failure mechanism of the
      coating was erosion of the binder phases, brittle detachment of hard phases and
      formation of pitting corrosion products.

PMID- 25617965
TI  - Lenalidomide and cyclophosphamide immunoregulation in patients with metastatic,
      castration-resistant prostate cancer.
AB  - Lenalidomide (LEN) and metronomic cyclophosphamide (CTX) regulate angiogenesis
      and immunosuppressive cells linked to the progression of metastatic castration
      resistant prostate cancer (mCRPC). A phase-I/II, dose-escalation trial of LEN
      plus oral CTX was conducted in patients with previously treated mCRPC. In the
      phase-I study, CTX was given at 50 mg (day 1-28) and LEN at 10-25 mg (day 1-21)
      on a 28-day cycle using a "3+3" study design. In phase II, patients received LEN
      at 25 mg (day 1-21) with CTX at 50 mg PO QD (day 1-28) on a 28-day cycle.
      Nineteen patients in phase I were evaluable for toxicity. The maximum tolerated
      dose (MTD) was not observed at any of the dose levels (DLs) tested. Six patients
      received treatment in phase II before the trial was closed. A >= 50% reduction in
      PSA was observed in 31.7% evaluable patients. Radiographically, one patient had a
      partial response. Stable disease was documented in 68% of evaluable patients
      after two therapy cycles. Circulating tumor cells (CTCs) decreased in 22.7% and
      remained stable in 31.8% of patients. Baseline numbers of peripheral MDSCs (MDSC;
      Lin-DR(-)CD11b(+)) were significantly increased in patients versus normal donors,
      and were decreased by chemotherapy. At baseline, MDSCs correlated directly with
      CTCs, and inversely with T- and B cell frequency supporting their
      immunosuppressive activity. The combination of LEN and metronomic CTX can be
      safely administered, reversing cellular immunosuppression in this group of
      elderly patients with mCRPC. Further research is required to identify responsive
      subgroup(s) and validate the biomarkers.

PMID- 25617968
TI  - A prospective study of blood splatter in ENT.
AB  - Surgeons face an occupational risk of daily exposure to blood and body fluids.
      Potential sources of infection include sharps injuries and mucocutaneous contact.
      The transmission of blood-borne viruses, in particular human immunodeficiency
      virus (HIV), Hepatitis B and Hepatitis C from the patient to healthcare workers
      is well documented in the literature. We studied the incidence and degree of
      blood splash in all otolaryngology (ENT) procedures undertaken in a single unit
      over a 12 week period. In addition, we investigated which intraoperative factors
      might predict the degree of splash. We undertook a prospective, non-blinded study
      of 102 patients undergoing a range of 'routine' elective ENT within one
      department over 12 weeks. A surgical mask with visor attached was worn in all
      procedures. Following each procedure, all splatter masks were collected and
      examined macroscopically and microscopically for blood splash. In addition, the
      procedure performed, technique used, total blood loss, operating time and grade
      of surgeon was noted. 54% of procedures resulted in splash mask contamination.
      The median number of splash spots per mask was 4.7 (range 0-63). Tonsillectomy
      was the most commonly performed procedure, accounting for over one-third of total
      procedures investigated. Each mask had an average of 8.2 splash marks.
      Tonsillectomy had a splash rate of 76.9%. Although the risk of developing HIV is
      low the operating surgeon has a duty to take all precautions to protect
      themselves during a procedure and therefore a protective mask and visor or
      suitable goggles must be worn.

PMID- 25617969
TI  - Diagnosis of glossopharyngeal obstruction using nasopharyngeal tube versus CT
      scan in obstructive sleep apnea-hypopnea syndrome.
AB  - The polysomnography after nasopharyngeal tube insertion (NPT-PSG) was used to
      assess glossopharyngeal airway obstruction in patients with moderate-to-severe
      obstructive sleep apnea-hypopnea syndrome (OSAHS), and was compared with that
      obtained using spiral computed tomography (CT). A total of 125 patients diagnosed
      with moderate-to-severe OSAHS using PSG were subjected to PSG after NPT
      insertion, and spiral CT was used for continuous scan of the upper respiratory
      tract. The NPT-PSG and CT scan results were subjected to correlation analysis. In
      addition, the two sets of data were used separately to determine whether there
      was glossopharyngeal airway stenosis or obstruction, and the results were
      compared. Neither apnea hypopnea index (AHI) nor lowest oxygen saturation (LSaO2)
      obtained from the first PSG was significantly correlated with the cross-sectional
      area or the inner diameter of the glossopharyngeal airway. NPT-PSG AHI was
      significantly correlated with the cross-sectional area and anteroposterior
      diameter of the glossopharyngeal airway, with correlation coefficients of 0.264
      and 0.185, and P values of 0.003 and 0.039, respectively. NPT-PSG AHI was not
      significantly correlated with the left-right diameter of the airway, and NPT-PSG
      LSaO2 was not significantly correlated with the cross-sectional area or the inner
      diameter of the glossopharyngeal airway. With NPT-PSG, 52 patients showed obvious
      glossopharyngeal airway stenosis while 73 patients did not, and with CT scan 41
      patients showed obvious glossopharyngeal airway stenosis while 84 patients did
      not. The two methods reached the same diagnosis in 86 cases, with a consistency
      rate of 68.8 %. Spiral CT and NPT-PSG show certain degrees of consistency by
      assessing the presence of glossopharyngeal airway stenosis or obstruction, and
      there are also notable differences. Clinical assessment on glossopharyngeal
      airway obstruction should be based on a combination of multiple methods.

PMID- 25617970
TI  - Short-term outcomes for laparoscopy-assisted distal gastrectomy for body mass
      index >=30 patients with gastric cancer.
AB  - BACKGROUND: Obesity is known to be a preoperative risk factor for gastric cancer
      surgery. This study aimed to investigate the influence of obesity on the surgical
      outcomes of laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer.
      METHODS: The clinical data of 131 patients with gastric cancer from January 2010
      December 2013 were analyzed retrospectively. Perioperative outcomes were compared
      between 43 patients with a body mass index (BMI) >=30 kg/m(2) (obese group) and
      88 patients with a BMI <30 kg/m(2) (nonobese group) who underwent LADG. RESULTS:
      Operation times were significantly longer for the obese group than for the
      nonobese group (234.1 +/- 57.2 min versus 212.2 +/- 43.5 min, P = 0.026). There
      were no statistically significant differences between two groups in terms of
      intraoperative blood loss, the number of retrieved lymph nodes, postoperative
      recovery, and postoperative complications (P > 0.05). During the follow-up period
      of 5 mo-49 mo (average, 36 mo), the overall survival rates were not significantly
      different between the two groups (80.0% [32/40] versus 81.9% [68/83], P > 0.05).
      The differences in recurrence and metastasis between the two groups were not
      statistically significant. CONCLUSIONS: Our analysis revealed that LADG can be
      safely performed in patients with BMI >=30. The procedure was considered to be
      difficult but sufficiently feasible.

PMID- 25617971
TI  - Systemic administration of hemoglobin improves ischemic wound healing.
AB  - BACKGROUND: Oxygen plays multifaceted roles in wound healing, including effects
      on cell proliferation, collagen synthesis, angiogenesis, and bacterial killing.
      Oxygen deficit is a major factor in the pathogenesis of chronic wounds. MATERIALS
      AND METHODS: We present a novel mechanism for oxygen delivery to ischemic wounds
      by systemic administration of an oxygen carrier substitute derived from bovine
      hemoglobin (IKOR 2084) in our ischemic rabbit ear wound model. The wound healing
      indexes, including epithelial gap and neo-granulation tissue area, were
      histologically analyzed. In situ expression of endothelial cells (CD31+) and
      proliferative cells (Ki-67+) were examined by immunohistochemistry analysis. The
      messenger RNA expression of collagen I, III, and vascular endothelial growth
      factor was measured by quantitative RT-PCR. Sirius Red staining was implemented
      for detection of collagen deposition, and terminal deoxynucleotidyl transferase
      dUTP nick end labeling analysis was performed to examine dermal cellular
      apoptosis. RESULTS: Systemic administration of IKOR 2084 significantly improved
      oxygen tension of ischemic tissue. When compared with saline controls, IKOR 2084
      treatment enhanced wound repair as demonstrated by a reduced epithelial gap and
      increased granulation tissue area. The expression of Ki-67+, CD31+, vascular
      endothelial growth factor and collagen was also enhanced by IKOR 2084
      administration. Moreover, apoptosis analysis in the wounds showed that cell
      survival in the dermis was increased by systemic IKOR 2084 administration.
      CONCLUSIONS: Our study suggests that systemic delivery of IKOR 2084 ameliorates
      hypoxic state, subsequently promotes angiogenesis, cellular proliferation, and
      collagen synthesis, attenuates hypoxia-induced apoptosis, and improved ischemic
      wound healing.

PMID- 25617972
TI  - Ex vivo heart perfusion after cardiocirculatory death; a porcine model.
AB  - BACKGROUND: Donation after cardiocirculatory death (DCD) has lead to an increase
      in organ availability. However, because of medical, logistic, and ethical issues,
      the use of hearts from DCD donors for transplantation is not generally considered
      to be feasible. In this study, we investigated the feasibility of ex vivo
      resuscitation and assessment of the porcine heart after circulatory death using
      the organ care system (OCS). METHODS: Cardiocirculatory death was induced in five
      pigs by cessation of mechanical ventilation. No heparin was administered. The
      agonal time (AT) was calculated as the time between a reduction of blood pressure
      <50 mm Hg or a fall in saturation beneath 70% and the cessation of electrical
      activity. After a further 15 min of warm ischemia, hearts were procured and
      implanted into the OCS, mimicking the actual clinical scenario for other organs.
      Thus, procured grafts were assessed ex vivo over a period of 4 h. RESULTS: Four
      hearts were successfully resuscitated on the system (AT 8, 15, 20, and 34 min)
      Three grafts had excellent visual contractility and lactate trends and were
      considered to be transplantable. One graft (AT 34 min) had an increased lactate
      and abnormal contractility being unsuitable for transplantation. One heart with
      48-min AT could not be resuscitated. CONCLUSIONS: Our data show that hearts from
      nonheparinized DCD porcine donors can be successfully resuscitated using the OCS
      in a scenario, which closely simulates clinical conditions.

PMID- 25617973
TI  - Nanomagnetic levitation three-dimensional cultures of breast and colorectal
      cancers.
AB  - BACKGROUND: Innovative technologies for drug discovery and development, cancer
      models, stem cell research, tissue engineering, and drug testing in various cell
      based platforms require an application similar to the in vivo system. MATERIALS
      AND METHODS: We developed for the first time nanomagnetically levitated three
      dimensional (3-D) cultures of breast cancer (BC) and colorectal cancer (CRC)
      cells using carbon-encapsulated cobalt magnetic nanoparticles. BC and CRC
      xenografts grown in severe combined immunodeficient (SCID) mice were evaluated
      for N-cadherin and epidermal growth factor receptor expressions. These phenotypes
      were compared with two-dimensional and 3-D cultures grown in a gel matrix.
      RESULTS: The BC and CRC cells grown by magnetic levitation formed microtissues.
      The levitated cultures had high viability and were maintained in culture for long
      periods of time. It has been observed that N-cadherin and epidermal growth factor
      receptor activities were highly expressed in the levitated 3-D tumor spheres and
      xenografts of CRC and BC cells. CONCLUSIONS: Nanomagnetically levitated 3-D
      cultures tend to form stable microtissues of BC and CRC and maybe more feasible
      for a range of applications in drug discovery or regenerative medicine.

PMID- 25617974
TI  - Cardioprotective Effects of Total Flavonoids Extracted from Xinjiang Sprig Rosa
      rugosa against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated
      Rat Heart.
AB  - This study evaluated the antioxidative and cardioprotective effects of total
      flavonoids extracted from Xinjiang sprig Rosa rugosa on ischemia/reperfusion
      (I/R) injury using an isolated Langendorff rat heart model. The possible
      mechanism of Xinjiang sprig rose total flavonoid (XSRTF) against I/R injury was
      also studied. XSRTF (5, 10, and 20 ug/mL) dissolved in Krebs-Henseleit buffer was
      administered to isolated rat heart. The XSRTF showed remarkable scavenging
      effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide anion
      radicals in vitro. XSRTF pretreatment improved the heart rate, increased LVDP,
      and decreased CK and LDH levels in coronary flow. This pretreatment also
      increased SOD activity and GSH/GSSG ratio but decreased MDA, TNF-alpha, and CRP
      levels and IL-8 and IL-6 activities. The infarct size and cell apoptosis in the
      hearts from the XSRTF-treated group were lower than those in the hearts from the
      I/R group. Therefore, the cardioprotective effects of XSRTF may be attributed to
      its antioxidant, antiapoptotic, and anti-inflammatory activities.

PMID- 25617975
TI  - [Treatment of obesity in a hospital endocrinology clinic. Influence of parental
      body mass index].
AB  - INTRODUCTION: Parental obesity is a risk factor for childhood obesity. The aim of
      this study was to determine if parental obesity influences the adherence and
      success of obesity treatment in a hospital paediatric endocrinology clinic.
      MATERIAL AND METHODS: An analytical, prospective, longitudinal study was
      conducted on obese children aged 4-14. An initial body mass index (BMI), and
      again at 6 months after receiving health, hygiene and dietary recommendations.
      Success was considered as a decrease of 0.5 in the BMI Z-score, and adherence to
      attending the 6-month review. Parental BMI was determined to identify overweight.
      The chi(2) test was used for qualitative variables and the T-Student test for
      quantitative (significance, p<<.05). RESULTS: The study included 100 children (52
      male), 9.9+/-2.7 years old, BMI 28.1+/- 4.5kg/m(2) and BMI Z-Score 3.11+/-0.98.
      (85% had a BMI Z-score>3). More than half (59%) of the children had one or both
      parents obese (41 fathers and 37 mothers were obese). Treatment was not adhered
      to by 25 children. Adherence was worse if both parents were obese OR 3.65 (1.3 to
      10.5) (P<=.01) and adherence was better if the mother was not obese, although the
      father was (P=.01). The treatment had significant success in 40 patients. If the
      mother was the only obese one in the family, the possibility of treatment failure
      was greater OR 5.6 (1.4 to 22.4) (P<.01) CONCLUSIONS: A high percentage of
      children with severe obesity have obese parents. The mother has an important
      influence on adherence and response to treatment for the severely obese child.

PMID- 25617976
TI  - [Aneurysmal bone cyst].

PMID- 25617977
TI  - [Community acquired pneumonia in children: Treatment of complicated cases and
      risk patients. Consensus statement by the Spanish Society of Paediatric
      Infectious Diseases (SEIP) and the Spanish Society of Paediatric Chest Diseases
      (SENP)].
AB  - The incidence of community-acquired pneumonia complications has increased during
      the last decade. According to the records from several countries, empyema and
      necrotizing pneumonia became more frequent during the last few years. The optimal
      therapeutic approach for such conditions is still controversial. Both
      pharmacological management (antimicrobials and fibrinolysis), and surgical
      management (pleural drainage and video-assisted thoracoscopic surgery), are the
      subject of continuous assessment. In this paper, the Spanish Society of
      Paediatric Infectious Diseases and the Spanish Society of Paediatric Chest
      Diseases have reviewed the available evidence. Consensus treatment guidelines are
      proposed for complications of community-acquired pneumonia in children, focusing
      on parapneumonic pleural effusion. Recommendations are also provided for the
      increasing population of patients with underlying diseases and immunosuppression.

PMID- 25617978
TI  - Microwave combustion synthesis of Co1-xZnxFe2O4 (0?x?0.5): Structural, magnetic,
      optical and vibrational spectroscopic studies.
AB  - Nanostructured pure and zinc doped cobalt ferrites (Co1-xZnxFe2O4 where x
      fraction ranging from 0 to 0.5) were prepared by microwave combustion method
      employing urea as a fuel. The nanostructured samples were characterized by using
      various instrumental techniques such as X-ray powder diffractometry, high
      resolution scanning electron microscopy, energy dispersive X-ray analysis, UV
      visible diffuse reflectance spectroscopy, photoluminescence spectroscopy and
      Fourier transformed infrared (FT-IR) spectroscopy. Vibrating sample magnetometry
      at room temperature was recorded to study the magnetic behavior of the samples. X
      ray analysis and the FT-IR spectroscopy revealed the formation of cobalt ferrite
      cubic spinel-type structure. The average crystallite sizes for the samples were
      in the range of 3.07-11.30 nm. The direct band gap (Eg) was estimated using
      Kubelka-Munk method and is obtained from the UV-vis spectra. The band gap value
      decreased with an increase in zinc fraction (2.56-2.17 eV). The violet and green
      emission observed in the photoluminescence spectra revealed that cobalt ferrites
      are governed by defect controlled processes. The elemental analysis of zinc doped
      cobalt ferrites were obtained from energy dispersive X-ray (EDX) analysis. From
      the magnetic measurements, it is observed that cobalt ferrite and zinc doped
      cobalt ferrite systems fall under the soft ferrite category. The saturation
      magnetization (Ms) value of undoped cobalt ferrite is 14.26 emu/g, and it has
      reached a maximum of 29.61 emu/g for Co0.7Zn0.3Fe2O4.

PMID- 25617979
TI  - Spectroscopic characterization of magnetic Fe3O4@Au core shell nanoparticles.
AB  - The magnetic nanoparticles iron oxide (Fe3O4) nanoparticles and iron oxide/gold
      core-shell (Fe3O4/Au) nanoparticles were synthesized and their catalytic photo
      degradation activity towards malathion as example of organophosphorus pesticides
      were reported. Iron oxide (Fe3O4) magnetic nanoparticle was successfully prepared
      through co-precipitation method by the reduction of ferric chloride (FeCl3) using
      ascorbic acid. The morphology of the prepared nanoparticles was characterized by
      the TEM and XRD (X-ray diffraction) techniques. Degradation of 10 ppm of
      malathion in the presence of these nanoparticles under UV radiation was monitored
      using (HPLC) and UV-visible spectra. Fe3O4/Au nanoparticles showed higher
      efficiency in photo-degradation of malathion than Fe3O4 ones.

PMID- 25617980
TI  - Synthesis and electrochromic, acidochromic properties of Schiff bases containing
      triphenylamine and thiophene units.
AB  - A series of Schiff bases (SBs) were designed and prepared from 2
      thiophenecarboxaldehyde and different triphenylamine (TPA) derivatives. The
      structures of the compounds were characterized by Fourier transform infrared (FT
      IR), hydrogen nuclear magnetic resonance (1H NMR). The optical and
      electrochemical properties were tested by ultraviolet-visible (UV-vis)
      spectroscopy and cyclic voltammetry (CV) techniques. The SBs exhibited stable and
      reversible electrochromic properties. Furthermore, multiple reversible colors
      states were also observed with the change of pH. Consequently, the SBs can be
      used as electrochromic and acidochromic materials.

PMID- 25617981
TI  - New size-expanded RNA nucleobase analogs: a detailed theoretical study.
AB  - Fluorescent nucleobase analogs have attracted much attention in recent years due
      to their potential applications in nucleic acids research. In this work, four new
      size-expanded RNA base analogs were computationally designed and their
      structural, electronic, and optical properties are investigated by means of DFT
      calculations. The results indicate that these analogs can form stable Watson
      Crick base pairs with natural counterparts and they have smaller ionization
      potentials and HOMO-LUMO gaps than natural ones. Particularly, the electronic
      absorption spectra and fluorescent emission spectra are calculated. The
      calculated excitation maxima are greatly red-shifted compared with their parental
      and natural bases, allowing them to be selectively excited. In gas phase, the
      fluorescence from them would be expected to occur around 526, 489, 510, and 462
      nm, respectively. The influences of water solution and base pairing on the
      relevant absorption spectra of these base analogs are also examined.

PMID- 25617982
TI  - Single excitation-emission fluorescence spectrum (EEF) for determination of
      cetane improver in diesel fuel.
AB  - A highly sensitive spectrofluorimetric method has been developed for the
      determination of 2-ethylhexyl nitrate in diesel fuel. Usually, this compound is
      used as an additive in order to improve cetane number. The analytical method
      consists in building the chemometric model as a first step. Then, it is possible
      to quantify the analyte with only recording a single excitation-emission
      fluorescence spectrum (EEF), whose data are introduced in the chemometric model
      above mentioned. Another important characteristic of this method is that the fuel
      sample was used without any pre-treatment for EEF. This work provides an interest
      improvement to fluorescence techniques using the rapid and easily applicable EEF
      approach to analyze such complex matrices. Exploding EEF was the key to a
      successful determination, obtaining a detection limit of 0.00434% (v/v) and a
      limit of quantification of 0.01446% (v/v). 

PMID- 25617983
TI  - Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.
AB  - Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme
      replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include
      patients with worsening motor function. Whether higher doses of ERT improve
      skeletal function in these patients has not been systematically studied. This
      exploratory, randomized, open-label, 52-week study examined the safety and
      efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2
      weeks) in 13 patients with Pompe disease and clinical decline or a lack of
      improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross
      reactive immunologic material assay-negative patients were excluded. Eleven of 13
      patients completed the study. Trends for improvement were seen in total gross
      motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4)
      of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4;
      infantile-onset, 7) showed improvement in motor and/or mobility skills. No
      between-regimen differences in efficacy emerged. Two case studies highlight the
      benefits of increased ERT dose in patients with Pompe disease experiencing
      clinical decline. Both alternative regimens were generally well tolerated. This
      study was limited by the small sample size, which is not uncommon for small
      clinical studies of rare diseases. Additionally, the study did not include direct
      assessment of muscle pathology, which may have identified potential causes of
      decreased response to ERT. Results were inconclusive but suggest that increased
      ERT dose may be beneficial in some patients with Pompe disease experiencing motor
      decline. Controlled studies are needed to clarify the benefits and risks of this
      strategy. 

PMID- 25617984
TI  - Medical anticancer treatment of lung cancer associated with comorbidities: a
      review.
AB  - Comorbidities are frequent in patients with lung cancer, who are often treated
      with systemic anticancer therapy. The purpose of the present review is to report
      the adaptations recommended for the various drugs used in lung cancer treatment,
      in the context of a specific comorbidity. The literature was reviewed for
      neurologic, endocrine, hepatic, renal, digestive, cardiovascular, pulmonary,
      blood and systemic diseases. The comorbidities impact on the systemic anticancer
      treatment is poorly assessed. There are no good data with a high level of
      evidence and literature is often limited to experts' opinion and to case reports.
      We need to improve our knowledge about those patients by adequate multicentric
      and prospective studies and registries in order to offer them better care in term
      of evidence-based medicine. 

PMID- 25617985
TI  - Prognosis of synchronous and metachronous multiple primary lung cancers:
      systematic review and meta-analysis.
AB  - BACKGROUND: With the development of imaging technology, an increasing number of
      multiple primary lung cancers (MPLC) are diagnosed in recent years. However,
      there is still ambiguity in the stage classification rules for patients with
      MPLC. Our purpose was to access the prognosis of synchronous and metachronous
      MPLC. METHODS: A systematic literature search was performed on four databases
      (EBSCO, Pubmed, OVID and Springer) to obtain relevant articles. We used published
      hazard ratios (HRs) of overall survival (OS) if available or estimates from the
      published survival data. RESULTS: There were 1796 patients with MPLC in 22
      relevant studies, who were eligible for analysis. We found that the OS of
      patients with synchronous MPLC was inferior to the one of metachronous MPLC
      patients when starting from the diagnosis of the first metachronous tumor (HR
      3.36, 95% CI 2.39-4.74; p<0.001). However, there was no difference when starting
      from the diagnosis of the second metachronous tumor (HR 1.19, 95% CI 0.86-1.66;
      p=0.29). From further analysis we found the OS of patients with MPLC was superior
      to that of patients with intrapulmonary metastasis (HR 2.66, 95% CI 1.30-5.44;
      p=0.007). Besides, we found no difference in OS between synchronous (HR 1.39, 95%
      CI 0.98-1.96; p=0.06) and metachronous (HR 1.05, 95% CI 0.75-1.47; p=0.77)
      patients, in spite of the histology. In terms of unilateral and bilateral MPLC
      patients, the OS had no difference either (HR 1.30, 95% CI 1.00-1.69; p=0.05).
      CONCLUSION: We found that MPLC had better OS than the lung cancer patients with
      intrapulmonary metastasis. And despite the tumor-free interval, the OS for
      metachronous MPLC was as good as that for synchronous MPLC. Furthermore, there
      was no difference of OS in different subgroups, including histology and position.

PMID- 25617986
TI  - Expression of insulin-like growth factor 1 receptor (IGF-1R) predicts poor
      responses to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      in non-small cell lung cancer patients harboring activating EGFR mutations.
AB  - OBJECTIVES: Expression of insulin-like growth factor 1 receptor (IGF-1R) in non
      small cell lung cancer (NSCLC) is associated with poor prognosis. The IGF-1R
      pathway activates downstream targets that bypass dependency in signals from the
      epidermal growth factor receptor (EGFR), which mediates resistance to EGFR
      tyrosine kinase inhibitors (TKIs). The aim of the present study was to determine
      the predictive role of IGF-1R expression in the response to EGFR-TKIs of NSCLC
      patients harboring activating EGFR mutations. MATERIALS AND METHODS: We
      retrospectively studied 62 NSCLC patients who had activating EGFR mutations and
      received TKIs. Protein expression of IGF-1R, vascular endothelial growth factor
      (VEGF), and human epidermal growth factor receptor 2 (HER2) were measured by
      immunohistochemical staining. Univariate and multivariate analyses were performed
      to identify predictive factors associated with the responses to EGFR-TKIs. The
      relationship of progression-free survival (PFS) with IGF-1R expression and the
      presence of diabetes mellitus (DM) were examined. RESULTS: Of 62 EGFR mutation
      positive patients, 26 expressed IGF-1R, and 13 had DM. In the multivariate
      analysis, young age, squamous cell carcinoma, and IGF-1R expression were
      independently associated with a shorter PFS after treatment with EGFR-TKIs.
      Patients expressing IGF-1R showed a significantly shorter PFS in response to EGFR
      TKIs compared with those lacking IGF-1R expression (9.1 vs. 20.1 months,
      p=0.005). The 13 patients with DM were more likely to express IGF-1R (p=0.001)
      and had shorter PFS times when treated with first-line EGFR-TKIs (7.6 vs. 18.6
      months, p=0.005), compared with those without DM. CONCLUSION: IGF-1R expression
      was a negative predictive factor for a response to EGFR-TKIs in NSCLC patients
      harboring activating EGFR mutations. Moreover, patients with DM highly expressed
      IGF-1R in tumor tissues, which was associated with a poor response to first-line
      TKI therapy. Further studies aimed at overcoming EGFR-TKI resistance will need to
      also address IGF-1R pathways.

PMID- 25617987
TI  - Azoospermia with variable testicular histology after 7 months of treatment with a
      deslorelin implant in toms.
AB  - The main aim of the study was to assess whether the longer use of a GnRH-agonist
      implant (deslorelin 4.7 mg, Suprelorin) in toms would lead to the suppression of
      spermatogenesis comparable with histologic appearance in juvenile animals as was
      previously described in dogs. The other aims were to monitor the progression of
      the testes size decrease and development of azoospermia 5 to 7 months after
      treatment with a GnRH-agonist implant. In animals, 5, 6, and 7 months after GnRH
      agonist implant insertion, variable histological appearance of germinal
      epithelium was found, when tubules with elongating spermatids, round spermatids,
      spermatocytes, and spermatogonia as the most developed germinal cells were found
      in each group of toms. In all male cats, 5, 6, and 7 months after implant
      insertion, testosterone concentrations and testes size significantly differed
      between the first and the last visit. All animals, except one tom castrated 5
      months after implant insertion, developed complete azoospermia. However, in this
      tom, all spermatozoa were immotile. Treatment with the subcutaneous GnRH-agonist
      implant was well tolerated, and no treatment-related adverse effects were noted.
      These results reported the efficacy of 4.7-mg deslorelin implant (Suprelorin)
      during its 7 months of use. The complete azoospermia confirms its contraceptive
      effect. However, the histologic evaluation revealed a great individual
      variability in the degree of spermatogenic suppression. The question as to
      whether spermatogenesis in toms can be suppressed in all males to the level of
      spermatogonia/primary spermatocytes after prolonged exposure to deslorelin has
      yet to be answered.

PMID- 25617988
TI  - Dietary alpha-linolenic acid from flaxseed oil or eicosapentaenoic and
      docosahexaenoic acids from fish oil differentially alter fatty acid composition
      and characteristics of fresh and frozen-thawed bull semen.
AB  - Incorporation rates of dietary omega-3 (n-3) fatty acids (FAs) from different
      sources into bull plasma and sperm and the effects on physiological
      characteristics of fresh and frozen-thawed semen were determined. Fifteen fertile
      bulls were assigned to three treatment groups and supplemented for 13 weeks with
      encapsulated fat: (1) SFA-360 g/d per bull saturated FA; (2) FLX-450 g/d per bull
      providing 84.2 g/d C18:3n-3 (alpha-linolenic acid) from flaxseed oil; and (3) FO
      450 g/d per bull providing 8.7 g/d C20:5n-3 (eicosapentaenoic acid) and 6.5 g/d
      C22:6n-3 (docosahexaenoic acid, DHA) from fish oil. Blood samples were taken
      every 2 weeks and semen was collected weekly. With respect to the FA supplements,
      the proportion of alpha-linolenic acid in plasma increased in the FLX bulls,
      whereas that of DHA was increased in the FO bulls, within 2 weeks. However,
      changes in the sperm FA fraction were first expressed in the sixth week of
      supplementation: in the FO and FLX bulls the DHA proportion increased (P <
      0.001), whereas that of C22:5n-6 FAs (docosapentaenoic acid [DPA] n-6) decreased
      (P < 0.001). Sperm motility and progressive motility in fresh semen were higher
      (P < 0.05), and the fading rate tended to be lower in the FLX than in FO bulls (P
      < 0.06). Furthermore, sperm motility, progressive motility, and velocity in
      frozen-thawed semen were higher in FLX than in the other groups (P < 0.008).
      These findings indicate that the proportion of DHA in sperm can be increased at
      the expense of DPAn-6 by either FO or FLX supplementation, indicating de novo
      elongation and desaturation of short- into longer-chain n-3 FAs in testes.
      Furthermore, the moderate exchange of DHA and DPAn-6 in the FLX group's sperm was
      associated with changes in the characteristics of both fresh and frozen-thawed
      semen, suggesting the importance of the ratio between these two FAs for sperm
      structure and function.

PMID- 25617989
TI  - Genetic variants in glucocorticoid and mineralocorticoid receptors are associated
      with concentrations of plasma cortisol, muscle glycogen content, and meat quality
      traits in male Nellore cattle.
AB  - The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are key
      components in the regulation of the hypothalamic-pituitary-adrenal neuroendocrine
      axis and coordinate the physiological response to stress agents to reestablish
      homeostasis. Genetic variations of GR (NR3C1) and MR (NR3C2) genes could explain
      the alterations in animals to adapt to challenges, and therefore, their influence
      on production traits. The present study aimed to identify single-nucleotide
      polymorphisms (SNPs) in the bovine NR3C1 and NR3C2 genes and explore their
      associations to relevant traits of beef cattle production. Genotypes and
      phenotypes were collected from 241 male Nellore cattle (119 noncastrated and 122
      castrated surgically) with an average of 24 +/- 1.2 mo of age and live weight of
      508 +/- 39 kg. The traits evaluated were concentrations of plasma
      adrenocorticotropic hormone (ACTH) and cortisol, muscle glycogen and lactate
      content, and pH, color, cooking loss, and shear force of longissimus thoracis
      measured on the 1st, 7th, and 14th days postmortem. Five SNPs were identified, 2
      in the NR3C1 gene and 3 in the NR3C2 gene. There was an associative relationship
      between the SNP NR3C1_1 g.3293A>G and postmortem plasma concentration of cortisol
      (P = 0.0008). The SNPs NR3C2_1 g.115T>C and NR3C2_2 g.570T>C were associated with
      muscle glycogen content (P = 0.0306 and P = 0.0158), postmortem plasma
      concentration of ACTH (P = 0.0118 and P = 0.0095), and cooking loss of the steak
      aged 1 d (P = 0.0398 and P = 0.0423). Haplotype analysis showed associations of
      GR haplotypes with postmortem plasma concentrations of cortisol and MR haplotypes
      with meat color, cooking losses, muscle glycogen content, and plasma
      concentrations of ACTH. The associations observed in the present study show that
      SNPs in GR and MR genes are related with changes of hypothalamic-pituitary
      adrenal axis activity and metabolic profile in cattle, leading to individual
      variation in meat quality traits.

PMID- 25617990
TI  - Comparison of different criteria for periodontitis case definition in head and
      neck cancer individuals.
AB  - PURPOSE: Different periodontitis case definitions have been used in clinical
      research and epidemiology. The aim of this study was to determine more accurate
      criterion for the definition of mild and moderate periodontitis case to be
      applied to head and neck cancer individuals before radiotherapy. METHODS: The
      frequency of periodontitis in a sample of 84 individuals was determined according
      to different diagnostic criteria: (1) Lopez et al. (2002);(2) Hujoel et al.
      (2006); (3) Beck et al. (1990); (4) Machtei et al. (1992); (5) Tonetti and
      Claffey (2005); (6) and Page and Eke (2007). All diagnosis were based on the
      clinical parameters obtained by a single calibrated examiner (Kw = 0.71). The
      individuals were evaluated before radiotherapy. They received oral hygiene
      instructions, and the cases diagnosed with periodontitis (Page and Eke 2007) were
      treated. The gold standard was the definition 6, and the others were compared by
      means of agreement, sensitivity (SS), specificity (SP), and the area under ROC
      curve. The kappa test evaluated the agreement between definitions. RESULTS: The
      frequency of periodontitis at baseline was 53.6 % (definition 1), 81.0 %
      (definition 2), 40.5 % (definition 3), 26.2 % (definition 4), 13.1 % (definition
      5), and 70.2 % (definition 6). The kappa test showed a moderate agreement between
      definitions 6 and 2 (59.0 %) and definitions 6 and 1 (56.0 %). The criterion with
      higher SS (0.92) and SP (0.73) was definition 1. CONCLUSION: Definition 1 was the
      most accurate criterion to case periodontitis definition to be applied to head
      and neck cancer individuals.

PMID- 25617991
TI  - Age-associated differences in global and segmental control during dual-task
      walking under sub-optimal sensory conditions.
AB  - The ability to safely perform cognitive-motor dual-tasks is critical for
      independence of older adults. We compared age-associated differences in global
      and segmental control during dual-task walking in sub-optimal sensory conditions.
      Thirteen young (YA) and 13 healthy older (OA) adults walked a straight pathway
      with cognitive dual-task of walking-while-talking (WT) or no-WT under four
      sensory conditions. On randomly selected trials, visual and vestibular inputs
      were manipulated using blurring goggles (BV) and Galvanic Vestibular Stimulation
      (GVS), respectively. Gait speed decreased more in YA than OA during WT. Gait
      speed increased with GVS with normal vision but not BV. Step length considerably
      decreased with WT. Trunk roll significantly decreased only in OA with GVS in WT.
      Head roll significantly decreased with GVS regardless of age. Results indicate
      GVS-induced adaptations were dependent on available visual information. YA
      reduced their gait speed more than OA to achieve a similar pace to safely perform
      WT. GVS resulted in both age-groups to reduce head movement. However, with the
      addition of WT during GVS, OA also stiffened their trunk. Therefore, with
      increased attentional demands healthy OA employed different compensatory
      strategies than YA to maintain postural control. 

PMID- 25617992
TI  - The role of eye movements in motor sequence learning.
AB  - An experiment that utilized a 16-element movement sequence was designed to
      determine the impact of eye movements on sequence learning. The participants were
      randomly assigned to two experimental groups: a group that was permitted to use
      eye movements (FREE) and a second group (FIX) that was instructed to fixate on a
      marker during acquisition (ACQ). A retention test (RET) was designed to provide a
      measure of learning, and two transfer tests were designed to determine the extent
      to which eye movements influenced sequence learning. The results demonstrated
      that both groups decreased the response time to produce the sequence, but the
      participants in the FREE group performed the sequence more quickly than
      participants of the FIX group during the ACQ, RET and the two transfer tests.
      Furthermore, continuous visual control of response execution was reduced over the
      course of learning. The results of the transfer tests indicated that oculomotor
      information regarding the sequence can be stored in memory and enhances response
      production. 

PMID- 25617993
TI  - Relationship between BMI, waist circumference, physical activity and probable
      developmental coordination disorder over time.
AB  - BACKGROUND: Cross-sectional studies have shown that children with developmental
      coordination disorder (DCD) are less likely to be physically active and have
      excess weight gain. However, longitudinal studies examining the relationship
      between DCD and measures of body composition (BMI and waist circumference) over
      time are lacking. It is not known if sex and physical activity affect the
      relationship between DCD and measures of body composition over time. OBJECTIVE:
      (1) To examine if BMI and waist circumference in children with and without
      probable DCD (pDCD) remain constant over time or change as children age, and
      whether this relationship varies by sex. (2) To examine if differences in
      physical activity between children with and without pDCD account for differences
      in BMI and waist circumference over time. METHODS: Physical Health Activity Study
      Team (PHAST) data were used for this longitudinal analysis. At baseline, a total
      of 2,278 (pDCD=103) children aged 9-10 years were included in the analysis. The
      total follow-up period was five years. Mixed-effects modeling was used to
      estimate change in body composition measures in children over time. RESULTS:
      Children with pDCD have higher BMI and waist circumference compared to typically
      developing children, and this difference increased over the study period. The
      relationship between pDCD and BMI over time also varied by sex. A similar trend
      was observed for waist circumference. Boys with pDCD were found to have a more
      rapid increase in BMI and waist circumference compared to girls with pDCD.
      Physical activity had neither a mediating nor a moderating effect on the
      relationship between pDCD and measures of body composition. However, physical
      activity was independently and negatively associated with measures of body
      composition. CONCLUSIONS: pDCD is associated with higher body mass and waist
      circumference, both important risk factors for cardiovascular disease, type 2
      diabetes, and psychological problems and other health conditions.

PMID- 25617994
TI  - Psychophysiological response to cognitive workload during symmetrical,
      asymmetrical and dual-task walking.
AB  - Walking with a lower limb prosthesis comes at a high cognitive workload for
      amputees, possibly affecting their mobility, safety and independency. A
      biocooperative prosthesis which is able to reduce the cognitive workload of
      walking could offer a solution. Therefore, we wanted to investigate whether
      different levels of cognitive workload can be assessed during symmetrical,
      asymmetrical and dual-task walking and to identify which parameters are the most
      sensitive. Twenty-four healthy subjects participated in this study. Cognitive
      workload was assessed through psychophysiological responses, physical and
      cognitive performance and subjective ratings. The results showed that breathing
      frequency and heart rate significantly increased, and heart rate variability
      significantly decreased with increasing cognitive workload during walking
      (p<.05). Performance measures (e.g., cadence) only changed under high cognitive
      workload. As a result, psychophysiological measures are the most sensitive to
      identify changes in cognitive workload during walking. These parameters reflect
      the cognitive effort necessary to maintain performance during complex walking and
      can easily be assessed regardless of the task. This makes them excellent
      candidates to feed to the control loop of a biocooperative prosthesis in order to
      detect the cognitive workload. This information can then be used to adapt the
      robotic assistance to the patient's cognitive abilities. 

PMID- 25617995
TI  - [Macrophage activation syndrome and autoimmunity due to visceral leishmaniasis].
AB  - Hemophagocytic syndromes are a heterogeneous group of diseases characterized by
      an excessive immune response, mediated by activated cytotoxic T cells and
      macrophages. Among hemophagocytic syndromes, genetic and secondary forms can be
      distinguished. We report on the case of a male newborn who presented with
      macrophage activation syndrome associated with lymphoproliferation with favorable
      outcome under prednisone and cyclosporin. Hemopathy, infection, or genetic
      lymphohistiocytosis were initially ruled out. Severe autoimmunity was suspected
      because of positive antinuclear antibodies and Farr test associated with anemia
      and a positive Coombs test as well as cytolytic hepatitis with anti-liver, kidney
      microsome (LKM) antibodies. Treatment was therefore intensified by adding
      mycophenolate mofetil. This led to an unexpected deterioration of general health
      and lab exam results with recurrence of fever and inflammation. The initial
      investigations were revisited and completed by a liver biopsy, which revealed the
      presence of numerous leishmania parasites at the amastigote stage, enabling the
      diagnosis of visceral leishmaniasis. The patient's condition dramatically
      improved under liposomal amphotericin B treatment. Our observation shows that
      visceral leishmaniasis can present as lupus-like syndrome with
      lymphoproliferation. Moreover, the lack of leishmania on marrow aspiration cannot
      rule out the diagnosis of visceral leishmaniasis. Detection of leishmania by
      serological or molecular tests is mandatory in case of hepatosplenomegaly with
      hemophagocytic syndrome together with autoantibodies, in order to avoid useless
      and life-threatening exposure to immunosuppressive treatments. 

PMID- 25617996
TI  - Contamination features and health risk of soil heavy metals in China.
AB  - China faces a big challenge of environmental deterioration amid its rapid
      economic development. To comprehensively identify the contamination
      characteristics of heavy metals in Chinese soils on a national scale, data set of
      the first national soil pollution survey was employed to evaluate the pollution
      levels using several pollution indicators (pollution index, geoaccumulation index
      and enrichment factor) and to quantify their exposure risks posed to human health
      with the risk assessment model recommended by the US Environmental Protection
      Agency. The results showed that, due to the drastically increased industrial
      operations and fast urban expansion, Chinese soils were contaminated by heavy
      metals in varying degrees. As a whole, the exposure risk levels of soil metals in
      China were tolerable or close to acceptable. Comparatively speaking, children and
      adult females were the relatively vulnerable populations for the non-carcinogenic
      and carcinogenic risks, respectively. Cadmium and mercury have been identified as
      the priority control metals due to their higher concentrations in soils or higher
      health risks posed to the public, as well as, arsenic, lead, chromium and nickel.
      Spatial distribution pattern analysis implied that the soil metal pollutions in
      southern provinces of China were relatively higher than that in other provinces,
      which would be related to the higher geochemical background in southwest regions
      and the increasing human activities in southeast areas. Meanwhile, it should be
      noticed that Beijing, the capital of China, also has been labeled as the priority
      control province for its higher mercury concentration. These results will provide
      basic information for the improvement of soil environment management and heavy
      metal pollution prevention and control in China. 

PMID- 25617997
TI  - Historical trends of PBDEs and HBCDs in sediment cores from Sydney estuary,
      Australia.
AB  - This paper presents the first historical data on the occurrence of polybrominated
      diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDs) in estuarine sediment
      from Australia. Sediment cores and surficial sediment samples were collected from
      four locations within Sydney estuary, Australia. Large increases in
      concentrations were observed for all compounds between 1980 and 2014, especially
      for BDE-209 (representative usage of Deca-BDE commercial mixture), which was
      found in surficial sediment at an average concentration of 42 ng/g dry wt (21-65
      ng/g dry wt). PBDE congeners representative of both the Penta- and Octa-BDE
      commercial mixtures (?6PBDEs) were also found in their highest concentrations in
      surficial sediments (average: 1.3 ng/g dry wt; range: 0.65-2.5 ng/g dry wt). PBDE
      concentrations in surficial sediments were relatively high when compared with
      those presented in the available literature. This suggests that their input into
      the Sydney estuary has not decreased since their bans almost a decade earlier.
      After a sharp increase in the 1990s, HBCD concentrations peaked at an average of
      3.5 ng/g dry wt (1.8-5.3 ng/g dry wt) in surficial samples. With global
      legislation on HBCDs allowing its usage for the next 10 years, it is expected
      that its input into the estuary is likely to continue.

PMID- 25617998
TI  - Turnover and release of P-, N-, Si-nutrients in the Mexicali Valley (Mexico):
      interactions between the lower Colorado River and adjacent ground- and surface
      water systems.
AB  - A study on dissolved nitrate, ammonium, phosphate and silicate concentrations was
      carried out in various water compartments (rivers, drains, channels, springs,
      wetland, groundwater, tidal floodplains and ocean water) in the Mexicali Valley
      and the Colorado River delta between 2012 and 2013, to assess modern potential
      nutrient sources into the marine system after river damming. While nitrate and
      silicate appear to have a significant input into the coastal ocean, phosphate is
      rapidly transformed into a particulate phase. Nitrate is, in general, rapidly bio
      consumed in the surface waters rich in micro algae, but its excess (up to 2.02 mg
      L(-1) of N from NO3 in winter) in the Santa Clara Wetland represents a potential
      average annual source to the coast of 59.4*10(3)kg N-NO3. Despite such localized
      inputs, continuous regional groundwater flow does not appear to be a source of
      nitrate to the estuary and coastal ocean. Silicate is associated with
      groundwaters that are also geothermally influenced. A silicate receiving
      agricultural drain adjacent to the tidal floodplain had maximum silicate
      concentrations of 16.1 mg L(-1) Si-SiO2. Seepage of drain water and/or mixing
      with seawater during high spring tides represents a potential source of dissolved
      silicate and nitrate into the Gulf of California.

PMID- 25617999
TI  - Are we waking up to the effects of NEFA?
AB  - NEFA are mobilised from adipose tissues during fasting or stress. Under
      conditions of acute or chronic NEFA excess, skeletal muscle and hepatic insulin
      resistance may ensue. Hence, a wealth of literature has focused on the crosstalk
      between NEFA and glucose in the pathogenesis of insulin resistance. Sleep
      restriction has also been shown to acutely induce insulin resistance, and self
      reported short sleep duration is associated with diabetes. In this issue of
      Diabetologia (DOI: 10.1007/s00125-015-3500-4), Broussard and colleagues examine
      the impact of acute sleep restriction on detailed 24 h metabolic profiles,
      including plasma NEFA. Here, we address the potential clinical relevance of these
      findings and pose questions for further research.

PMID- 25618000
TI  - Sleep Medicine journal year in review.

PMID- 25618001
TI  - Vapor intrusion attenuation factors relative to subslab and source, reconsidered
      in light of background data.
AB  - The basis upon which recommended attenuation factors for vapor intrusion (VI)
      have been derived are reconsidered. By making a fitting curve to the plot showing
      the dependence of observed indoor air concentration (c(in)) on subslab
      concentration (c(ss)) for residences in EPA database, an analytical equation is
      obtained to identify the relationship among c(in), css and the averaged
      background level. The new relationship indicates that subslab measurements may
      serve as a useful guide only if c(ss) is above 500 MUg/m(3). Otherwise, c(in) is
      independent of c(ss), with a distribution in good agreements with other studies
      of background levels. Therefore, employing this screening value (500 MUg/m(3)),
      new contaminant concentration attenuation factors are proposed for VI, and the
      values for groundwater-to-indoor and subslab-to-indoor air concentration
      attenuation factors are 0.004 and 0.02, respectively. The former is applied to
      examining the reported temporal variations of c(in) obtained during a long-term
      monitoring study. The results show that using this new groundwater-to-indoor air
      concentration attenuation factor also provides a reasonably conservative estimate
      of c(in).

PMID- 25618002
TI  - Treatment-as-usual (TAU) is anything but usual: a meta-analysis of CBT versus TAU
      for anxiety and depression.
AB  - OBJECTIVES: There were three aims of this study, the first was to examine the
      efficacy of CBT versus treatment-as-usual (TAU) in the treatment of anxiety and
      depressive disorders, the second was to examine how TAU is defined in TAU control
      groups for those disorders, and the third was to explore whether the type of TAU
      condition influences the estimate of effects of CBT. METHOD: A systematic search
      of Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL was
      conducted. RESULTS: 48 studies of CBT for depressive or anxiety disorders
      (n=6926) that specified that their control group received TAU were identified.
      Most (n=45/48) provided an explanation of the TAU group however there was
      significant heterogeneity amongst TAU conditions. The meta-analysis showed medium
      effects favoring CBT over TAU for both anxiety (g=0.69, 95% CI 0.47-0.92,
      p<0.001, n=1318) and depression (g=0.70, 95% CI 0.49-0.90, p<0.001, n=5054), with
      differential effects observed across TAU conditions. CONCLUSIONS: CBT is superior
      to TAU and the size of the effect of CBT compared to TAU depends on the nature of
      the TAU condition. The term TAU is used in different ways and should be more
      precisely described. The four key details to be reported can be thought of as
      "who, what, how many, and any additional treatments?"

PMID- 25618003
TI  - Suicidality and its relationship with depression, alcohol disorders and childhood
      experiences of violence: results from the ESEMeD study.
AB  - BACKGROUND: Suicidality constitutes a major health concern in many countries. The
      aim of the present paper was to analyse 10 of its risk factors and their
      interdependence. METHODS: Data on suicidality, mental disorders and experience of
      childhood violence was collected from 8796 respondents in the European Study of
      the Epidemiology of Mental Disorders (ESEMeD). The CIDI was used to assess mental
      disorders. Individuals were randomly divided into two subgroups. In one, a
      Graphical Markov model to predict suicidality was constructed, in the second,
      predictors were cross-validated. RESULTS: Lifetime suicidality was predicted
      mainly by lifetime depression and early experiences of violence, with a pseudo R
      square of 12.8%. In addition, alcohol disorders predicted suicidality, but played
      a minor role compared with the other risk factors in this sample. CONCLUSION: In
      addition to depression, early experience of violence constitutes an important
      risk factor of suicidality. LIMITATIONS: This is a cross-sectional and
      retrospective study assessing risk factors for suicidality, not for suicide
      itself.

PMID- 25618004
TI  - The Impact of Suicide on Co-patients.
AB  - While there is a large literature on the impact of patient suicide on care
      providers and on family members, and a small literature on the impact of hospital
      suicide on inpatients and on surviving members of a therapy group, nothing has
      been written about the effect of a suicide on patients in a community mental
      health facility. This paper discusses the potential for ripple effects and the
      need for extra care and surveillance when a patient commits suicide in an
      outpatient program for the seriously mentally ill. The paper draws on related
      literature (suicide in groups, hospitals, schools, and college campuses) and,
      using examples from a clinic for women with psychosis, makes recommendations for
      psychiatric intervention post suicide. After the trauma of suicide, staff needs
      protected time to inform and support survivors, taking special care with those
      seen as most vulnerable. Following a trauma such as suicide, patients tend to
      stay near a source of comfort, and may require extra staff time. Survivors need
      to make sense of what happened and to honor the dead. This brings privacy
      concerns to the fore, as well as staff ambivalence about the respect due to a
      person who should be remembered, but should not serve as a role model to fellow
      patients who are susceptible to contagion effects. The review that follows a
      suicide can lead to closure for staff and patients and to the development of a
      protocol to follow should similar incidents recur. 

PMID- 25618005
TI  - Decreased face primary motor cortex (face-M1) excitability induced by noxious
      stimulation of the rat molar tooth pulp is dependent on the functional integrity
      of face-M1 astrocytes.
AB  - Acute inflammatory dental pain is a prevalent condition often associated with
      limited jaw movements. Mustard oil (MO, a small-fiber excitant/inflammatory
      irritant) application to the rat molar tooth pulp induces increased excitability
      (i.e., central sensitization) of trigeminal medullary dorsal horn (MDH)
      nociceptive neurons that can be modulated by MDH application of the astrocytic
      inhibitor methionine sulfoximine (MSO). The objectives of the study were to
      determine whether MO application to the rat right maxillary first molar tooth
      pulp affects left face-M1 excitability manifested as altered intracortical
      microstimulation thresholds for evoking electromyographic activity in the right
      anterior digastric (RAD, jaw-opening muscle), and whether MSO application to face
      M1 can modulate this MO effect. Under Ketamine general anesthesia, Sprague-Dawley
      male rats had a microelectrode positioned at a low-threshold (<=30 MUA) face-M1
      site. Then MO (n = 16) or control solution (n = 16) was applied to the previously
      exposed tooth pulp, and RAD threshold was monitored for 15 min. MSO (0.1 mM, n =
      8) or saline (n = 8) was then applied to the face-M1, and RAD thresholds were
      monitored every 15 min for 120 min. ANOVA followed by post hoc Bonferroni was
      used to analyze data (p < 0.05). Within 15 min of MO (but not control) pulp
      application, RAD thresholds increased significantly (p < 0.001) as compared to
      baseline. One hour following MSO (but not saline) application to the face-M1, RAD
      thresholds decreased significantly (p = 0.005) toward baseline. These novel
      findings suggest that acute inflammatory dental pain is associated with decreased
      face-M1 excitability that may be dependent on the functional integrity of face-M1
      astrocytes and related to mechanisms underlying limited jaw movements in acute
      orofacial pain conditions.

PMID- 25618006
TI  - Mere observation of body discontinuity affects perceived ownership and vicarious
      agency over a virtual hand.
AB  - The mental representation of one's body typically implies the continuity of its
      parts. Here, we used immersive virtual reality to explore whether mere
      observation of visual discontinuity between the hand and limb of an avatar could
      influence a person's sense of ownership of the virtual body (feeling of
      ownership, FO) and being the agent of its actions (vicarious agency, VA). In
      experiment 1, we tested whether placing different amounts of visual discontinuity
      between a virtual hand and limb differently modulate the perceived FO and VA.
      Participants passively observed from a first-person perspective four different
      versions of a virtual limb: (1) a full limb; a hand detached from the proximal
      part of the limb because of deletion of (2) the wrist; (3) the wrist and forearm;
      (4) and the wrist, forearm and elbow. After observing the static or moving
      virtual limb, participants reported their feeling of ownership (FO) and vicarious
      agency (VA) over the hand. We found that even a small visual discontinuity
      between the virtual hand and arm significantly decreased participants' FO over
      the hand during observation of the static limb. Moreover, in the same condition,
      we found that passive observation of the avatar's actions induced a decrease in
      both FO and VA. We replicated the same results in a second study (experiment 2)
      where we investigated the modulation of FO and VA by comparing the visual body
      discontinuity with a condition in which the virtual limb was partially occluded.
      Our data show that mere observation of limb discontinuity can change a person's
      ownership and agency over a virtual body observed from a first-person
      perspective, even in the absence of any multisensory stimulation of the real
      body. These results shed new light on the role of body visual continuity in
      modulating self-awareness and agency in immersive virtual reality. 

PMID- 25618007
TI  - On the bimanual integration of proprioceptive information.
AB  - Proprioception can be defined as the sense for body movement and position. While
      most sensory information can be successfully integrated across hemispheres,
      little is known about the bilateral integration of proprioceptive information. In
      two behavioural experiments, we investigated whether estimates of the position of
      one hand are influenced by simultaneous proprioceptive information from the other
      hand. We further investigated whether such putative bimanual proprioceptive
      integration would differ between expert dancers and non-dancer controls. Either
      one hand or both hands were passively moved to novel positions, and participants
      indicated the perceived location of the index finger tip of the designated target
      hand, by orienting a visible laser beam mounted on a cap. Synchronized bimanual
      movements compared to unimanual movements significantly improved proprioceptive
      position sense. In particular, we found a bias reduction to perceive the target
      hand's index finger tip as shifted away from the midline in the bimanual
      condition, compared to the unimanual condition. Expert dancers, in contrast, did
      not show this change in proprioceptive position sense after bimanual movements.
      We suggest that bimanual movements may improve proprioception due to
      interhemispheric integration in controls, but not in expert dancers.

PMID- 25618009
TI  - Developmentally distinct gaze processing systems: luminance versus geometric
      cues.
AB  - Two experiments examined how the different cues to gaze direction contribute to
      children's abilities to follow and make explicit judgements about gaze. In each
      study participants were shown blurred images of faces containing only luminance
      cues to gaze direction, line-drawn images containing only fine-grained detail
      supporting a geometric analysis of gaze direction, and unmanipulated images. In
      Experiment 1a, 2- and 3-year olds showed gaze-cued orienting of attention in
      response to unmanipulated and blurred faces, but not line-drawn faces. Adult
      participants showed cueing effects to line drawn faces as well as the other two
      types of face cue in Experiment 1b. In Experiment 2, 2-year-olds were poor at
      judging towards which of four objects blurred and line-drawn faces were gazing,
      whereas 3- and 4-year-olds performed above chance with these faces. All age
      groups performed above chance with unmanipulated images. These findings are
      consistent with an early-developing luminance-based mechanism, which supports
      gaze following, but which cannot initially support explicit judgements, and a
      later-developing mechanism, additionally using geometric cues in the eye, which
      supports explicit judgements about gaze. 

PMID- 25618008
TI  - The perception-action dynamics of action competency are altered by both physical
      and observational training.
AB  - Action competency is defined as the ability of an individual to self-evaluate
      their own performance capabilities. The current experiment demonstrated that
      physical and observational training with a motor skill alters action competency
      ratings in a similar manner. Using a pre-test and post-test protocol, the results
      revealed that action competency is constrained prior to training by the intrinsic
      dynamics of relative phase (phi), with in-phase (phi = 0 degrees ) and anti-phase
      (phi = 180 degrees ) patterns receiving higher competency ratings than other
      relative phase patterns. After 2 days of training, action competency ratings for
      two trained relative phase patterns, +60 degrees  and +120 degrees , increased
      following physical practice or observational practice. A transfer test revealed
      that both physical performance ability and action competency ability transferred
      to the symmetry partners (-60 degrees  and -120 degrees ) of the two trained
      relative phase patterns following physical or observational training. The
      findings also revealed that relative motion direction acts as categorical
      information that helps to organize action production and facilitate action
      competency. The results are interpreted based on the coordination dynamics theory
      of perception-action coupling, and extend this theory by showing that visual
      perception, action production, and action competency are all constrained in a
      consistent manner by the dynamics of the order parameter relative phase. As a
      whole, the findings revealed that relative motion, relative phase, and possibly
      relative amplitude information are all distinct sources of information that
      contribute to the emergence of a kinematic understanding of action in the nervous
      system.

PMID- 25618010
TI  - Generality and specificity in the effects of musical expertise on perception and
      cognition.
AB  - Performing musicians invest thousands of hours becoming experts in a range of
      perceptual, attentional, and cognitive skills. The duration and intensity of
      musicians' training - far greater than that of most educational or rehabilitation
      programs - provides a useful model to test the extent to which skills acquired in
      one particular context (music) generalize to different domains. Here, we asked
      whether the instrument-specific and more instrument-general skills acquired
      during professional violinists' and pianists' training would generalize to
      superior performance on a wide range of analogous (largely non-musical) skills,
      when compared to closely matched non-musicians. Violinists and pianists
      outperformed non-musicians on fine-grained auditory psychophysical measures, but
      surprisingly did not differ from each other, despite the different demands of
      their instruments. Musician groups did differ on a tuning system perception task:
      violinists showed clearest biases towards the tuning system specific to their
      instrument, suggesting that long-term experience leads to selective perceptual
      benefits given a training-relevant context. However, we found only weak evidence
      of group differences in non-musical skills, with musicians differing marginally
      in one measure of sustained auditory attention, but not significantly on auditory
      scene analysis or multi-modal sequencing measures. Further, regression analyses
      showed that this sustained auditory attention metric predicted more variance in
      one auditory psychophysical measure than did musical expertise. Our findings
      suggest that specific musical expertise may yield distinct perceptual outcomes
      within contexts close to the area of training. Generalization of expertise to
      relevant cognitive domains may be less clear, particularly where the task context
      is non-musical. 

PMID- 25618011
TI  - Parathyroid adenoma upstaging the lung cancer.
AB  - Mediastinal staging of NSCLC with noninvasive methods such as PET/CT can be
      misleading when a mediastinal disease accompany. Histopathologic confirmation
      should be made before any treatment plan. Herein, we presented a case of
      parathyroid adenoma upstaging the lung cancer. 

PMID- 25618012
TI  - High-uptake areas on positron emission tomography with the hypoxic radiotracer
      (18)F-FRP170 in glioblastomas include regions retaining proliferative activity
      under hypoxia.
AB  - OBJECTIVE: The aim was to evaluate the proliferative activity of high-uptake
      areas on positron emission tomography (PET) with the hypoxic cell radiotracer, 1
      (2-[(18)F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP170).
      METHODS: Thirteen patients with glioblastoma underwent FRP170 PET before tumor
      resection. During surgery, tumor specimens were stereotaxically obtained from
      regions corresponding to high (high-uptake areas, HUAs) and relatively low (low
      uptake areas, LUAs) accumulation of FRP170. We compared immunohistochemical
      staining for Ki-67 and hypoxia-inducible factor (HIF)-1alpha between HUA and LUA.
      RESULTS: HIF-1alpha index was significantly higher in HUAs than in LUAs. In
      contrast, mean Ki-67 indices did not differ significantly between HUAs and LUAs.
      CONCLUSIONS: Findings for HIF-1alpha index clearly indicated that HUAs on FRP170
      PET represented hypoxic regions in glioblastoma. However, findings of Ki-67 index
      suggest that HUAs on FRP170 PET include regions retaining proliferative activity
      regardless of tissue hypoxia.

PMID- 25618014
TI  - Indenopyrazole oxime ethers: synthesis and beta1-adrenergic blocking activity.
AB  - This paper reports the synthesis and cardiac activity of new beta-blockers
      derived from (Z/E)-indeno[1,2-c]pyrazol-4(1H)-one oximes (5a,b). The latter
      compounds were allowed to react with epichlorohydrin, followed by reacting the
      oxiranyl derivatives formed (6a,b) with some aliphatic amines to give the target
      compounds (Z/E)-1-phenyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3
      (substituted amino)propyl)oxime (7a-c) and (Z/E)-1-methyl-1H-indeno[1,2-c]pyrazol
      4-one O-((2-hydroxy-3-(substituted amino)propyl)oxime (8a-c). These final
      products 7a-c and 8a-c were evaluated for their ability to modulate the cardiac
      performance of a prototype mammalian heart. The results showed that, out of these
      molecules tested, 7b elicits a more potent depressant effect on contractility and
      relaxation, and competitively antagonizes beta1-adrenergic receptors. 

PMID- 25618013
TI  - Associations of objectively measured built-environment attributes with youth
      moderate-vigorous physical activity: a systematic review and meta-analysis.
AB  - BACKGROUND: Understanding attributes of the built environment that influence
      children's and adolescents' habitual physical activity can inform urban design.
      OBJECTIVE: To conduct a systematic review and meta-analysis of studies linking
      aspects of the built environment with youth moderate-vigorous activity, including
      walking. DATA SOURCES: The PubMed, Embase, and Cumulative Index to Nursing and
      Allied Health Literature (CINAHL) databases were searched using relevant key
      words for articles published between January 2000 and March 2013. STUDY
      SELECTION: The included articles reported associations between children's or
      adolescents' objectively measured physical activity and residential
      neighbourhoods or activity settings defined with geographical information systems
      (GIS), street audits or global positioning systems (GPS). Excluded articles did
      not delineate neighbourhoods by residential address or were not written in
      English. Of 320 potentially relevant articles, 31 met the inclusion criteria, but
      only 23 (with a total of 6,175 participants, aged 8-17 years) provided sufficient
      data to derive effects (associations) of built-environment features on child or
      adolescent habitual moderate-vigorous activity. STUDY APPRAISAL AND SYNTHESIS
      METHODS: Ten criteria were used to appraise the inclusion of studies. The effects
      were analysed as the difference in mean minutes of daily moderate-vigorous
      activity either between two levels of a dichotomous variable (e.g., neighbourhood
      park available or not within 800 m) or between predicted means corresponding to a
      difference of two standard deviations of a simple linear numeric variable (e.g.,
      housing density per square kilometre). The magnitude of the difference in means
      was evaluated via standardization. The meta-analysis was performed with the 14
      studies using GIS or street audits to relate a total of 58 specific built
      environment features to daily activity. Each feature was categorized with two
      dichotomous variables to indicate whether the feature promoted playing and/or
      walking, and these variables were included in the meta-analytic model as
      moderators interacting with age and proportion of males in the study as linear
      numeric covariates. RESULTS: The meta-analysed effects of built-environment
      features that encourage play (including sports and fitness) and/or walking on
      youth moderate-vigorous activity ranged between trivial and small. There was a
      moderate effect of age (15 versus 9 years) whereby play facilities, parks,
      playgrounds and features that facilitate walking had negative effects on
      children's activity but positive effects on adolescents' activity. In studies
      that located youth physical activity with GPS, walking to school produced small
      increases in activity compared with transport by car or bus, greater proportions
      of activity took place in streets and urban venues (40-80%) than in green spaces
      (20-50%), and more than half of children's outdoor activity occurred with a
      parent nearby. LIMITATIONS: The meta-analysis cannot quantify the additive effect
      when several built-environment features are provided in a given neighbourhood.
      CONCLUSIONS: Children do not benefit to the same extent as adolescents from built
      environment features that encourage walking and those designed or used for
      neighbourhood play.

PMID- 25618015
TI  - Synthesis, anticancer and radiosensitizing evaluation of some novel sulfonamide
      derivatives.
AB  - In this study, novel series of sulfonamide derivatives were synthesized starting
      from 2-cyanoacetyl)hydrazono)ethyl)phenyl)benzenesulfonamide 4a and 2
      cyanoacetyl)hydrazono)ethyl)phenyl)-4-methylbenzenesulfonamide 4b. Different
      biologically active moieties as pyrazol, thiophene, pyridine and pyrimidines were
      introduced in order to investigate their in-vitro anticancer activity, in
      addition to a novel series of sulfonamide chalcones were synthesized from the
      reported 4-acetyl-N-(P-tolyl) benzenesulfonamide 3b. The newly synthesized
      sulfonamide derivatives were characterized by FT-IR, (1)H NMR, (13)C NMR, mass
      spectroscopy and elemental analyses and were tested for their in-vitro anticancer
      activity against human tumor liver cell line (HEPG-2). The most potent compounds
      in this study were compounds 4a, 4b, 5a, 6a, 6b, 8, 9, 11, 13, 18 and 19 which
      showed higher activity than doxorubicin with IC50 ranging from 11.0 to 31.8 MUM.
      Additionally, eight compounds among the most potent were evaluated for their
      ability to enhance the cell killing effect of gamma-radiation. 

PMID- 25618017
TI  - Synthesis and antitumor activity of ring A modified 11-keto-beta-boswellic acid
      derivatives.
AB  - Beta-boswellic acids are interesting triterpenoic acids that show different
      biological activities. Their cytotoxic potential, as well as that of their
      derivates remained unexploited so far. In this study we were able to prepare
      derivatives of 11-keto-beta-boswellic acid that showed lower IC50 values as
      determined by a sulphorhodamine B (SRB) assay using several different human
      tumour cell lines. Thus, the introduction of an amino group at position C-2 led
      to a significantly improved cytotoxic activity of amine 18. An apoptotic effect
      of compound 18 was determined using DNA laddering and trypan blue staining
      experiments. 

PMID- 25618018
TI  - Microwave-assisted synthesis of certain pyrrolylpyridines, some derived ring
      systems and their evaluation as anticancer and antioxidant agents.
AB  - The synthesis of 18 novel pyrrolylpyridines and some derived bi-, tri- and
      tetracyclic ring systems using both the conventional heating and MW irradiation
      techniques is described. Fourteen compounds; 2-9, 10-12, 14, 17 and 18 were
      evaluated for their antitumor activity according to the National Cancer Institute
      (NCI), in vitro disease oriented antitumor screening. Distinctive antitumor
      activity was conjugated with compounds 3 and 7 (R = 3,4-di-OCH3-C6H3). The
      analogs 3, 6, 7, 9, 10, 11 and 12 which exhibited prominent antitumor activity,
      were further evaluated for their antioxidant potential using the DPPH radical
      scavenging assay. The substituted 6-(3,4-dimethoxyphenyl)pyridine-3-carbonitriles
      3 and 7 were nearly equipotent to BHT the standard antioxidant utilized in this
      assay (scavenging activity 31 and 33%, respectively, vs 36%). Accordingly,
      compounds 3 and 7 can be considered as lead structures for dual antitumor and
      antioxidant activities. 

PMID- 25618016
TI  - Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and
      resistant strains of Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is a major public health concern worldwide with over 2 billion
      people currently infected. The rise of strains of Mycobacterium tuberculosis
      (Mtb) that are resistant to some or all first and second line antibiotics,
      including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally
      drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are
      urgently needed. Curcumin, a natural product used in traditional medicine in
      India, exhibits anti-microbial activity that includes Mtb, however it is
      relatively unstable and suffers from poor bioavailability. To improve activity
      and bioavailability, mono-carbonyl analogs of curcumin were synthesized and
      screened for their capacity to inhibit the growth of Mtb and the related
      Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we
      found several analogs that inhibit in vitro growth of Mm and Mtb, including
      rifampicin-resistant strains. Structure activity analysis of the analogs
      indicated that Michael acceptor properties are critical for inhibitory activity.
      However, no synergistic effects were evident between the monocarbonyl analogs and
      rifampicin on inhibiting growth. Together, these data provide a structural basis
      for the development of analogs of curcumin with pronounced anti-mycobacterial
      activity and provide a roadmap to develop additional structural analogs that
      exhibit more favorable interactions with other anti-TB drugs.

PMID- 25618019
TI  - Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with
      antineoplastic compounds.
AB  - Antineoplastic compounds are used in the treatment of a variety of cancers. The
      effectiveness of an antineoplastic compound to exert its activity is largely
      dependent on transport proteins involved in the entry of the compound into the
      cells, and those which drive it out of the cell. Organic anion transporting
      polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3
      (OATP1B3), belonging to the SLCO family of proteins, are specifically expressed
      in the sinusoidal membranes of the liver, and are known to interact with a
      variety of drugs. The present study deals with the interaction of these proteins
      with antineoplastic compounds routinely used in cancer chemotherapy. The proteins
      OATP1B1 and OATP1B3 were functionally characterized in stably transfected human
      embryonic kidney cells using [(3)H] labeled estrone 3-sulfate and [(3)H] labeled
      cholecystokinin octapeptide (CCK-8) as substrates, respectively. Substrate uptake
      experiments performed in the presence of antineoplastic compounds showed that
      vinblastine and paclitaxel strongly interacted with the OATP1B1 with Ki values of
      10.2 MUM and 0.84 MUM, respectively. OATP1B3 showed highly significant
      interactions with a variety of antineoplastic compounds including chlorambucil,
      mitoxantrone, vinblastine, vincristine, paclitaxel and etoposide, with Ki values
      of 40.6 MUM, 3.2 MUM, 15.9 MUM, 30.6 MUM, 1.8 MUM and 13.5 MUM, respectively. We
      report several novel interactions of the transporter proteins OATP1B1 and OATP1B3
      highlighting the need to investigate their role in drug-drug interactions and
      cancer chemotherapy. 

PMID- 25618020
TI  - Design, synthesis, and antiviral activity of novel rutin derivatives containing
      1, 4-pentadien-3-one moiety.
AB  - Rutin (compound 5) and some compounds (compounds 1-4 and 6) were isolated from
      Artemisia princeps Pamp (A. princeps Pamp.) and a series of novel rutin
      derivatives containing 1,4-pentadien-3-one moiety were designed and synthesized.
      The target compounds were characterized by proton nuclear magnetic resonance
      spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C
      NMR), and ESI-MS. Bioassay results indicated that some of the compounds showed
      good to excellent antiviral activities against tobacco mosaic virus (TMV) and
      cucumber mosaic virus (CMV) at 500 MUg/mL in vivo. The 50% effective
      concentrations (EC50) of the compound 7r against CMV was 394.78 MUg/mL, which was
      better than that of Ningnanmycin (432.22 MUg/mL). These results indicated that
      novel rutin derivatives containing 1,4-pentadien-3-one moiety can effectively
      control CMV. 

PMID- 25618021
TI  - Rapid determination of polycyclic aromatic hydrocarbons in grilled meat using
      microwave-assisted extraction and dispersive liquid-liquid microextraction
      coupled to gas chromatography-mass spectrometry.
AB  - A simple and rapid analytical tech nique for the simultaneous determination of 16
      polycyclic aromatic hydrocarbons (PAHs) in grilled meat was developed using
      microwave-assisted extraction and dispersive liquid-liquid microextraction (MAE
      DLLME) followed by gas chromatography-mass spectrometry (GC-MS). The effective
      parameters in DLLME process were optimized. Good linear relationships were
      obtained for 16 PAHs in a range of 1-200 ng g(-1), with a correlation coefficient
      (R(2)) higher than 0.98. Limits of detection and limits of quantification were
      0.15-0.3 ng g(-1) and 0.47-1 ng g(-1), respectively. The relative standard
      deviations (RSD%) for seven analyses were less than 9%. The recoveries of those
      compounds in grilled meat were obtained from 85% to 104%. Low consumption of the
      solvent, high recovery, short extraction time, no matrix interference and good
      merit figures compared to other methods are advantages of the proposed method.
      The performance of the present method was evaluated for the determination of PAHs
      in various types of real grilled meat samples, and satisfactory results were
      obtained.

PMID- 25618022
TI  - Graph analysis of the anatomical network organization of the hippocampal
      formation and parahippocampal region in the rat.
AB  - Graph theory was used to analyze the anatomical network of the rat hippocampal
      formation and the parahippocampal region (van Strien et al., Nat Rev Neurosci
      10(4):272-282, 2009). For this analysis, the full network was decomposed along
      the three anatomical axes, resulting in three networks that describe the
      connectivity within the rostrocaudal, dorsoventral and laminar dimensions. The
      rostrocaudal network had a connection density of 12% and a path length of 2.4.
      The dorsoventral network had a high cluster coefficient (0.53), a relatively high
      path length (1.62) and a rich club was identified. The modularity analysis
      revealed three modules in the dorsoventral network. The laminar network contained
      most information. The laminar dimension revealed a network with high clustering
      coefficient (0.47), a relatively high path length (2.11) and four significantly
      increased characteristic network building blocks (structural motifs). Thirteen
      rich club nodes were identified, almost all of them situated in the
      parahippocampal region. Six connector hubs were detected and all of them were
      located in the entorhinal cortex. Three large modules were revealed, indicating a
      close relationship between the perirhinal and postrhinal cortex as well as
      between the lateral and medial entorhinal cortex. These results confirmed the
      central position of the entorhinal cortex in the (para)hippocampal network and
      this possibly explains why pathology in this region has such profound impact on
      cognitive function, as seen in several brain diseases. The results also have
      implications for the idea of strict separation of the "spatial" and the "non
      spatial" information stream into the hippocampus. This two-stream memory model
      suggests that the information influx from, respectively, the postrhinal-medial
      entorhinal cortex and the perirhinal-lateral entorhinal cortex is separate, but
      the current analysis shows that this apparent separation is not determined by
      anatomical constraints.

PMID- 25618023
TI  - Structure elucidation of a galactofuranose-rich heteropolysaccharide from
      aciduric fungus penicillium purpurogenum JS03-21.
AB  - The exopolysaccharide-producing fungus Penicillium purpurogenum JS03-21 from the
      acidic purple clay was screened to develop greater insights into microbial
      exopolysaccharide resources from extremophilic microorganisms. An
      exopolysaccharide JS1-1 was purified from the fermented broth of the aciduric
      fungus using a combination of ethanol precipitation, anion-exchange and size
      exclusion chromatography. JS1-1 was found to be a neutral heteropolysaccharide
      composed of galactose, mannose and glucose in the ratio of 7.9:2.1:1.0, with a
      molecular weight of about 26 kDa. JS1-1 was subjected to a series of methylation
      and partial acid hydrolysis reactions, as well as being analyzed by one- and two
      dimensional nuclear magnetic resonance, and the results of these analyses
      revealed JS1-1 to be a galactofuranose-rich polysaccharide. The main chain of JS1
      1 contained two regions, including a galactose part composed of a repeating
      trisaccharide unit [i.e., ->5)-beta-D-Galf(1 -> 5)-beta-D-Galf(1 -> 6)-beta-D
      Galf(1->], and a mannose section consisting of (1 -> 6)-linked alpha-D-Manp
      residues. Two further segments [i.e., alpha-D-Glcp(1 -> 2)-alpha-D-Galf (1 -> and
      alpha-D-Galf(1 -> 2)-alpha-D-Manp(1->] existed as branches that were linked to
      the O-2 atoms of the (1 -> 6)-beta-D-Galf and (1 -> 6)-alpha-D-Manp regions of
      the main chain, respectively. The results of the current study demonstrate that
      JS1-1 is a unique polysaccharide that is rich in both alpha and beta
      galactofuranose units and therefore different from most of the other known
      extracellular polysaccharides. The function of this polysaccharide is currently
      being researched in our laboratory. 

PMID- 25618024
TI  - A constitutive model for the time-dependent, nonlinear stress response of fibrin
      networks.
AB  - Blood clot formation is important to prevent blood loss in case of a vascular
      injury but disastrous when it occludes the vessel. As the mechanical properties
      of the clot are reported to be related to many diseases, it is important to have
      a good understanding of their characteristics. In this study, a constitutive
      model is presented that describes the nonlinear viscoelastic properties of the
      fibrin network, the main structural component of blood clots. The model is
      developed using results of experiments in which the fibrin network is subjected
      to a large amplitude oscillatory shear (LAOS) deformation. The results show three
      dominating nonlinear features: softening over multiple deformation cycles, strain
      stiffening and increasing viscous dissipation during a deformation cycle. These
      features are incorporated in a constitutive model based on the Kelvin-Voigt
      model. A network state parameter is introduced that takes into account the
      influence of the deformation history of the network. Furthermore, in the period
      following the LAOS deformation, the stiffness of the networks increases which is
      also incorporated in the model. The influence of cross-links created by factor
      XIII is investigated by comparing fibrin networks that have polymerized for 1 and
      2 h. A sensitivity analysis provides insights into the influence of the eight fit
      parameters. The model developed is able to describe the rich, time-dependent,
      nonlinear behavior of the fibrin network. The model is relatively simple which
      makes it suitable for computational simulations of blood clot formation and is
      general enough to be used for other materials showing similar behavior. 

PMID- 25618026
TI  - Exploring the 'Healthy Migrant Paradox' in Sweden. A Cross Sectional Study
      Focused on Perinatal Outcomes.
AB  - Evidence shows that in some contexts immigrants have better health than natives
      in spite of coming from poorer socioeconomic contexts and of facing socioeconomic
      disadvantages in the host country. However, this is a country or origin- and
      outcome-specific phenomenon. This study compares different health outcomes
      derived from birthweight and gestational age among different migrant groups
      residing in Sweden. Cross-sectional study based on the Swedish Medical Birth
      Register for years 1987-1993. Multinomial regression models were performed to
      obtain crude and adjusted Odd Ratios and their 95 % Confidence Intervals.
      Overall, immigrants show a higher risk of LBW and preterm and a lower risk of
      macrosomia and post-term. Moreover, some groups performed worse than natives even
      in indicators at the two ends of the distribution. The healthy migrant paradox is
      also outcome-specific within different perinatal indicators and the selection
      explanation cannot fully account for this phenomenon. 

PMID- 25618025
TI  - European Hernia Society guidelines on the closure of abdominal wall incisions.
AB  - BACKGROUND: The material and the surgical technique used to close an abdominal
      wall incision are important determinants of the risk of developing an incisional
      hernia. Optimising closure of abdominal wall incisions holds a potential to
      prevent patients suffering from incisional hernias and for important costs
      savings in health care. METHODS: The European Hernia Society formed a Guidelines
      Development Group to provide guidelines for all surgical specialists who perform
      abdominal incisions in adult patients on the materials and methods used to close
      the abdominal wall. The guidelines were developed using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) approach and
      methodological guidance was taken from Scottish Intercollegiate Guidelines
      Network (SIGN). The literature search included publications up to April 2014. The
      guidelines were written using the AGREE II instrument. An update of these
      guidelines is planned for 2017. RESULTS: For many of the Key Questions that were
      studied no high quality data was detected. Therefore, some strong recommendations
      could be made but, for many Key Questions only weak recommendations or no
      recommendation could be made due to lack of sufficient evidence. RECOMMENDATIONS:
      To decrease the incidence of incisional hernias it is strongly recommended to
      utilise a non-midline approach to a laparotomy whenever possible. For elective
      midline incisions, it is strongly recommended to perform a continuous suturing
      technique and to avoid the use of rapidly absorbable sutures. It is suggested
      using a slowly absorbable monofilament suture in a single layer aponeurotic
      closure technique without separate closure of the peritoneum. A small bites
      technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current
      recommended method of fascial closure. Currently, no recommendations can be given
      on the optimal technique to close emergency laparotomy incisions. Prophylactic
      mesh augmentation appears effective and safe and can be suggested in high-risk
      patients, like aortic aneurysm surgery and obese patients. For laparoscopic
      surgery, it is suggested using the smallest trocar size adequate for the
      procedure and closure of the fascial defect if trocars larger or equal to 10 mm
      are used. For single incision laparoscopic surgery, we suggest meticulous closure
      of the fascial incision to avoid an increased risk of incisional hernias.

PMID- 25618027
TI  - Evaluation of coronary adventitial vasa vasorum using 3D optical coherence
      tomography--animal and human studies.
AB  - OBJECTIVES: This study sought to evaluate adventitial vasa vasorum (VV) in vivo
      with novel imaging technique of optical coherence tomography (OCT). METHODS: To
      verify OCT methods for quantification of VV, we first studied 2 swine carotid
      arteries in a model of focal angiogenesis by autologous blood injection, and
      compared microchannel volume (MCV) by OCT and VV by m-CT, and counts of those. In
      OCT images, adventitial MC was identified as signal-voiding areas which were
      located within 1 mm from the lumen-intima border. After manually tracing
      microchannel areas and the boundaries of lumen-intima and media-adventitial in
      all slices, we reconstructed 3D images. Moreover, we performed with OCT imaging
      in 8 recipients referred for evaluation of cardiac allograft vasculopathy at 1
      year after heart transplantation. MCV and plaque volume (PV) were assessed with
      3D images in each 10-mm-segment. RESULTS: In the animal study, among the 16
      corresponding 1-mm-segments, there were significant correlations of count and
      volume between both the modalities (count r(2) = 0.80, P < 0.01; volume r(2) =
      0.50, P < 0.01) and a good agreement with a systemic bias toward underestimation
      with m-CT. In the human study, there was a significant positive correlation
      between MCV and PV (segment number = 24, r(2) = 0.63, P < 0.01). CONCLUSION: Our
      results suggest that evaluation of MCV with 3D OCT imaging might be a novel
      method to estimate the amount of adventitial VV in vivo, and further has the
      potential to provide a pathophysiological insight into a role of the VV in
      allograft vasculopathy.

PMID- 25618028
TI  - Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing
      sites of apolipoprotein B gene and review of the literature.
AB  - OBJECTIVE: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant
      disorder of lipoprotein metabolism characterized by low plasma levels of total
      cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein
      B (apoB) below the 5(th) percentile of the distribution in the population.
      Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely
      rare and few patients have been characterized at the molecular level. Here we
      report the medical history and the molecular characterization of one paediatric
      patient with clinical features of Ho-FHBL. METHODS: A one month old infant with
      failure to thrive, severe hypocholesterolemia and acanthocytosis was clinically
      and genetically characterized. Molecular characterization of the proband and her
      parents was performed by direct sequencing of the APOB gene and functional role
      of the identified mutations was assessed by the minigene methodology. RESULTS:
      The proband was found carrying two novel splicing mutations of the APOB gene
      (c.3696+1G > C and c.3697-1G > A). CHOK1H8 cells expressing minigenes harbouring
      the mutations showed that these two mutations were associated with the retention
      of intron 23 and skipping of exon 24, resulting in two truncated apoB fragments
      of approximate size of 26-28 % of ApoB-100 and the total absence of apoB.
      CONCLUSION: We describe the first case of Ho-FHBL due to two splicing mutations
      affecting both the donor and the acceptor splice sites of the same intron of the
      APOB gene occurring in the same patient. The clinical management of the proband
      is discussed and a review of the clinical and genetic features of the published
      Ho-FHBL cases is reported.

PMID- 25618029
TI  - Association of circulating sclerostin with vascular calcification in Afro
      Caribbean men.
AB  - OBJECTIVE: Sclerostin, a Wingless (Wnt) pathway antagonist, is an established
      regulator of bone mineralization in humans but its potential importance in the
      regulation of vascular calcification is less clear. Therefore, our objective was
      to assess the relationship of serum sclerostin levels with coronary and aortic
      artery calcification (CAC and AAC, respectively) in Afro-Caribbean men on the
      island of Tobago. METHODS: Serum sclerostin levels and computed tomography of CAC
      and AAC were measured in 191 men (age mean(SD): 62.9(8.0)years) recruited without
      regard to health status. Multivariable logistic regression models were used to
      assess the cross-sectional association of sclerostin with prevalent arterial
      calcification. RESULTS: Mean(SD) sclerostin was 45.2 pmol/L (15.6 pmol/L). After
      adjusting for risk factors including age, physical and lifestyle characteristics,
      comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level
      was associated with a 1.61-times (95%CI 1.02-2.53) greater odds of having CAC.
      Sclerostin was not associated with AAC in any model. CONCLUSIONS: This is the
      first study to show that, among Afro-Caribbean men, greater serum sclerostin
      concentrations were associated with prevalence and extent of CAC. Further studies
      are needed to better define the role of the Wnt signaling pathway in arterial
      calcification in humans.

PMID- 25618030
TI  - CD1d serves as a surface receptor for oxidized cholesterol induction of
      peroxisome proliferator-activated receptor-gamma.
AB  - OBJECTIVE: The cluster of differentiation-1d (CD1d) recognizes and presents the
      lipid antigens to NK-T lymphocytes. Atherosclerotic lesions contain atherogenic
      lipids, mainly cholesterol and its oxides. Peroxisome proliferator-activated
      receptor-gamma (PPARgamma) is also known to exist in atherosclerotic lesions,
      participating in regulation of lipid metabolism. The current study tested whether
      CD1d acts as a surface receptor that mediates induction and activation of
      PPARgamma by oxysterols commonly found in atherosclerotic lesions. METHODS AND
      RESULTS: CD1d overexpression in HEK 293 cells transfected with CD1d cDNA was
      confirmed by fluorescence, flow cytometry, Western blotting and mRNA expression.
      Tritiated ((3)H) 7-ketocholesterol (7K) was used for lipid binding assays.
      Radioactive assessment demonstrated an increased 7K-binding activity HEK 293
      cells with CD1d overexpression. The 7K binding could be blocked by another
      oxysterol, 25-hydroxycholesterol, but not by native free cholesterol. Addition of
      CD1d:IgG dimer protein or an anti-CD1d antibody, but not control IgG,
      significantly diminished 7K binding to CD1d-expressing HEK 293 cells. CD1d
      deficiency markedly diminished the 7K-binding in macrophages and smooth muscle
      cells. Western blot and gel shift assays demonstrated that CD1d-mediated 7K
      binding induced expression and activation of PPARgamma. The PPARgamma agonist
      PGJ2 enhances the 7K stimulatory effect on PPARgamma expression and activity but
      the antagonist GW9662 inhibits the 7K effect on the CD1d-expressing cells.
      CONCLUSIONS: CD1d acts as a cell surface receptor that recognizes and binds
      oxysterols and initializes a pathway connecting oxysterol binding to PPARgamma
      activation.

PMID- 25618032
TI  - Cost-effectiveness of statin treatment for primary prevention in conditions of
      real-world adherence--estimates from the Finnish prescription register.
AB  - OBJECTIVE: To estimate the cost-effectiveness of statin therapy for primary
      prevention of coronary heart disease (CHD) events under real-world adherence.
      METHODS: A cost-effectiveness model was applied to estimate the expected 10-year
      costs and health outcomes (in terms of quality-adjusted life-years, QALYs)
      associated with and without statin treatment (at defined adherence levels) among
      hypothetical cohorts of Finnish men and women who were initially without
      established CHD. Treatment efficacy, cost, and quality of life estimates were
      obtained from published sources. Long-term treatment adherence was measured based
      on data from the national prescription register. RESULTS: At an assumed
      willingness-to-pay threshold of ?20,000 per QALY gained, statin treatment with
      real-world adherence was cost-effective among the older patient groups when the
      patients' 10-year CHD risk was as high as 20% and did not seem cost-effective in
      the youngest age groups. Conversely, statin treatment with full adherence was
      cost-effective for almost all patient groups with a 10-year CHD risk of at least
      15%. CONCLUSIONS: Even though generic statins are now low-cost drugs, treatment
      adherence seems to have a major impact on the cost-effectiveness of statin
      treatment in primary prevention. This finding stresses the importance of making a
      concerted effort for improving adherence among patients on statin therapy to
      obtain full benefit of the investment in statins. Therefore, novel cost-effective
      approaches to improve treatment adherence are warranted.

PMID- 25618033
TI  - Repertoire and classification of non-song calls in Southeast Alaskan humpback
      whales (Megaptera novaeangliae).
AB  - On low-latitude breeding grounds, humpback whales produce complex and highly
      stereotyped songs as well as a range of non-song sounds associated with breeding
      behaviors. While on their Southeast Alaskan foraging grounds, humpback whales
      produce a range of previously unclassified non-song vocalizations. This study
      investigates the vocal repertoire of Southeast Alaskan humpback whales from a
      sample of 299 non-song vocalizations collected over a 3-month period on foraging
      grounds in Frederick Sound, Southeast Alaska. Three classification systems were
      used, including aural spectrogram analysis, statistical cluster analysis, and
      discriminant function analysis, to describe and classify vocalizations. A
      hierarchical acoustic structure was identified; vocalizations were classified
      into 16 individual call types nested within four vocal classes. The combined
      classification method shows promise for identifying variability in call
      stereotypy between vocal groupings and is recommended for future classification
      of broad vocal repertoires. 

PMID- 25618034
TI  - Automated acoustic localization and call association for vocalizing humpback
      whales on the Navy's Pacific Missile Range Facility.
AB  - Time difference of arrival (TDOA) methods for acoustically localizing multiple
      marine mammals have been applied to recorded data from the Navy's Pacific Missile
      Range Facility in order to localize and track humpback whales. Modifications to
      established methods were necessary in order to simultaneously track multiple
      animals on the range faster than real-time and in a fully automated way, while
      minimizing the number of incorrect localizations. The resulting algorithms were
      run with no human intervention at computational speeds faster than the data
      recording speed on over forty days of acoustic recordings from the range,
      spanning multiple years. Spatial localizations based on correlating sequences of
      units originating from within the range produce estimates having a standard
      deviation typically 10 m or less (due primarily to TDOA measurement errors), and
      a bias of 20 m or less (due primarily to sound speed mismatch). An automated
      method for associating units to individual whales is presented, enabling
      automated humpback song analyses to be performed.

PMID- 25618035
TI  - Compensating for the effects of site and equipment variation on delphinid species
      identification from their echolocation clicks.
AB  - A concern for applications of machine learning techniques to bioacoustics is
      whether or not classifiers learn the categories for which they were trained.
      Unfortunately, information such as characteristics of specific recording
      equipment or noise environments can also be learned. This question is examined in
      the context of identifying delphinid species by their echolocation clicks. To
      reduce the ambiguity between species classification performance and other
      confounding factors, species whose clicks can be readily distinguished were used
      in this study: Pacific white-sided and Risso's dolphins. A subset of data from
      autonomous acoustic recorders located at seven sites in the Southern California
      Bight collected between 2006 and 2012 was selected. Cepstral-based features were
      extracted for each echolocation click and Gaussian mixture models were used to
      classify groups of 100 clicks. One hundred Monte-Carlo three-fold experiments
      were conducted to examine classification performance where fold composition was
      determined by acoustic encounter, recorder characteristics, or recording site.
      The error rate increased from 6.1% when grouped by acoustic encounter to 18.1%,
      46.2%, and 33.2% for grouping by equipment, equipment category, and site,
      respectively. A noise compensation technique reduced error for these grouping
      schemes to 2.7%, 4.4%, 6.7%, and 11.4%, respectively, a reduction in error rate
      of 56%-86%. 

PMID- 25618031
TI  - Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on
      atherosclerotic plaque progression and stability.
AB  - OBJECTIVE: Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin
      (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been
      associated with a 2-3 fold increased incidence of atherothrombosis in individuals
      with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not
      homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated
      with the Hp 2-2 genotype has been shown to be prevented with vitamin E
      supplementation in man. We sought to determine if there was an interaction
      between the Hp genotype and vitamin E on atherosclerotic plaque growth and
      stability in a transgenic model of the Hp polymorphism. METHODS AND RESULTS:
      Brachiocephalic artery atherosclerotic plaque volume was serially assessed by
      high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-)
      background. Hp 2-2 mice had more rapid plaque growth and an increased incidence
      of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth
      in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction
      between the Hp genotype and vitamin E on plaque growth. CONCLUSIONS: These
      results may help explain why vitamin E supplementation in man can prevent CVD in
      Hp 2-2 DM but not in non Hp 2-2 DM individuals.

PMID- 25618036
TI  - Cross-correlation, triangulation, and curved-wavefront focusing of coral reef
      sound using a bi-linear hydrophone array.
AB  - A seven element, bi-linear hydrophone array was deployed over a coral reef in the
      Papahanaumokuakea Marine National Monument, Northwest Hawaiian Islands, in order
      to investigate the spatial, temporal, and spectral properties of biological sound
      in an environment free of anthropogenic influences. Local biological sound
      sources, including snapping shrimp and other organisms, produced curved-wavefront
      acoustic arrivals at the array, allowing source location via focusing to be
      performed over an area of 1600 m(2). Initially, however, a rough estimate of
      source location was obtained from triangulation of pair-wise cross-correlations
      of the sound. Refinements to these initial source locations, and source frequency
      information, were then obtained using two techniques, conventional and adaptive
      focusing. It was found that most of the sources were situated on or inside the
      reef structure itself, rather than over adjacent sandy areas. Snapping-shrimp
      like sounds, all with similar spectral characteristics, originated from
      individual sources predominantly in one area to the east of the array. To the
      west, the spectral and spatial distributions of the sources were more varied,
      suggesting the presence of a multitude of heterogeneous biological processes. In
      addition to the biological sounds, some low-frequency noise due to distant
      breaking waves was received from end-fire north of the array. 

PMID- 25618039
TI  - Uncertainty analysis of standardized measurements of random-incidence absorption
      and scattering coefficients.
AB  - This work presents an analysis of the effect of some uncertainties encountered
      when measuring absorption or scattering coefficients in the reverberation chamber
      according to International Organization for Standardization/American Society for
      Testing and Materials standards. This especially relates to the uncertainty due
      to spatial fluctuations of the sound field. By analyzing the mathematical
      definition of the respective coefficient, a relationship between the properties
      of the chamber and the test specimen and the uncertainty in the measured quantity
      is determined and analyzed. The validation of the established equations is
      presented through comparisons with measurement data. This study analytically
      explains the main sources of error and provides a method to obtain the product of
      the necessary minimum number of measurement positions and the band center
      frequency to achieve a given maximum uncertainty in the desired quantity. It is
      shown that this number depends on the ratio of room volume to sample surface area
      and the reverberation time of the empty chamber. 

PMID- 25618037
TI  - Sound localization in common vampire bats: acuity and use of the binaural time
      cue by a small mammal.
AB  - Passive sound-localization acuity and the ability to use binaural time and
      intensity cues were determined for the common vampire bat (Desmodus rotundus).
      The bats were tested using a conditioned suppression/avoidance procedure in which
      they drank defibrinated blood from a spout in the presence of sounds from their
      right, but stopped drinking (i.e., broke contact with the spout) whenever a sound
      came from their left, thereby avoiding a mild shock. The mean minimum audible
      angle for three bats for a 100-ms noise burst was 13.1 degrees -within the range
      of thresholds for other bats and near the mean for mammals. Common vampire bats
      readily localized pure tones of 20 kHz and higher, indicating they could use
      interaural intensity-differences. They could also localize pure tones of 5 kHz
      and lower, thereby demonstrating the use of interaural time-differences, despite
      their very small maximum interaural distance of 60 MUs. A comparison of the use
      of locus cues among mammals suggests several implications for the evolution of
      sound localization and its underlying anatomical and physiological mechanisms.

PMID- 25618038
TI  - Low frequency baleen whale calls detected on ocean-bottom seismometers in the Lau
      basin, southwest Pacific Ocean.
AB  - Ten months of broadband seismic data, recorded on six ocean-bottom seismographs
      located in the Lau Basin, were examined to identify baleen whale species. As the
      first systematic survey of baleen whales in this part of the southwest Pacific
      Ocean, this study reveals the variety of species present and their temporal
      occurrence in and near the basin. Baleen whales produce species-specific low
      frequency calls that can be identified by distinct patterns in data spectrograms.
      By matching spectrograms with published accounts, fin, Bryde's, Antarctic blue,
      and New Zealand blue whale calls were identified. Probable whale sounds that
      could not be matched to published spectrograms, as well as non-biologic sounds
      that are likely of volcanogenic origin, were also recorded. Detections of fin
      whale calls (mid-June to mid-October) and blue whale calls (June through
      September) suggest that these species migrate through the region seasonally.
      Detections of Bryde's whale calls (primarily February to June, but also other
      times of the year) suggest this species resides around the basin nearly year
      round. The discovery of previously unpublished call types emphasizes the limited
      knowledge of the full call repertoires of baleen whales and the utility of using
      seismic survey data to enhance understanding in understudied regions. 

PMID- 25618040
TI  - Perceptual thresholds for realistic double-slope decay reverberation in large
      coupled spaces.
AB  - Reverberation highly influences sound perception in enclosed spaces. The
      reverberation time (RT) metric, used to quantify reverberation in single volumes,
      is inappropriate for coupled spaces characterized by non-exponential double-slope
      energy decays. Previous research on reverberation perception of double-slope
      decays has been predominantly based on varying basic impulse response
      characteristics such as decay times corresponding to reverberation times of
      individual volumes presented as independent variables. Alternatively, several
      studies have employed geometrical room acoustic software simulations to generate
      collections of responses while varying architectural parameters such as coupling
      area and room volumes. To avoid issues related to geometrical acoustics
      simulations, such as position dependence and limitations of some software to
      properly simulate coupled volume behavior, this study examines perception of the
      variability of reverberation typical of a physical coupled volume system.
      Employing an established statistical model, the control parameter of coupling
      area aperture which acoustically connects the volumes serves as the independent
      variable. Two listening tests were conducted to determine perceptual thresholds
      using an ABX discrimination task. The range of tested values corresponded to
      physically realizable variations. Just noticeable differences (JNDs) were derived
      with an average JND of ~ 10% variation of the coupling aperture. No significant
      differences were found between different musical excerpts. 

PMID- 25618041
TI  - Chinese speech intelligibility and its relationship with the speech transmission
      index for children in elementary school classrooms.
AB  - The present study investigated Chinese speech intelligibility in 28 classrooms
      from nine different elementary schools in Guangzhou, China. The subjective
      Chinese speech intelligibility in the classrooms was evaluated with children in
      grades 2, 4, and 6 (7 to 12 years old). Acoustical measurements were also
      performed in these classrooms. Subjective Chinese speech intelligibility scores
      and objective speech intelligibility parameters, such as speech transmission
      index (STI), were obtained at each listening position for all tests. The
      relationship between subjective Chinese speech intelligibility scores and STI was
      revealed and analyzed. The effects of age on Chinese speech intelligibility
      scores were compared. Results indicate high correlations between subjective
      Chinese speech intelligibility scores and STI for grades 2, 4, and 6 children.
      Chinese speech intelligibility scores increase with increase of age under the
      same STI condition. The differences in scores among different age groups decrease
      as STI increases. To achieve 95% Chinese speech intelligibility scores, the STIs
      required for grades 2, 4, and 6 children are 0.75, 0.69, and 0.63, respectively. 

PMID- 25618042
TI  - Advantages of the incoherent uniform theory of diffraction for acoustic
      calculations in open-plan offices.
AB  - Sound prediction in open-plan offices is a real challenge for room acoustics
      models because of the large dimensions involved and because of the complexity of
      the interior layout. For these reasons, the geometrical theory, based on a high
      frequency hypothesis, is often cited as an advantageous solution. Two types of
      approaches are, in general, developed under this hypothesis: the phase-included
      approach and the energy-based or "incoherent" approach. In this paper,
      comparisons are presented between calculations performed using these two
      approaches and measurements conducted in the laboratory where workstations were
      separated by low dividers and placed under ceilings that were absorbent to
      various extents. Particular attention was paid to processing diffraction using
      the uniform theory of diffraction. Narrow-band comparisons between calculations
      and measurements show that the phase-included model is flawed at low frequencies
      whenever the characteristic dimensions of the elements of the room (desk, low
      divider, etc.) are of the same order of magnitude as the wavelength. Conversely,
      the incoherent formulation, which removes the part played by the interference,
      gives results at least as accurate, be it in octave band or overall. Boasting
      very short computation times, the incoherent approach opens up interesting
      prospects for acoustic predictions in large open-plan offices. 

PMID- 25618043
TI  - Experimental investigation of chair type, row spacing, occupants, and carpet on
      theatre chair absorption.
AB  - This paper examines how the individual variations of chair type, row spacing, as
      well as the presence of occupants and carpet, combine to influence the absorption
      characteristics of theater chairs as a function of sample perimeter-to-area (P/A)
      ratios. Scale models were used to measure the interactive effects of the four
      test variables on the chair absorption characteristics, avoiding the practical
      difficulties of full scale measurements. All of the test variables led to effects
      that could lead to important changes to auditorium acoustics conditions. At mid
      and higher frequencies, the various effects can usually be explained as due to,
      more or less, porous absorbing material. In the 125 and 250 Hz octave bands, the
      major changes were attributed to resonant absorbing mechanisms. The results
      indicate that for accurate predictions of the effective absorption of the chairs
      in an auditorium, one should use the P/A method and reverberation chamber tests
      of the chair absorption coefficients to predict the absorption coefficients of
      each block of chairs and use these results as input in a room acoustics computer
      model of the auditorium. The application of these results to auditorium acoustics
      design is described, more approximate approaches are considered, and relations to
      existing methods are discussed.

PMID- 25618044
TI  - Prediction of the niche effect for single flat panels with or without attached
      sound absorbing materials.
AB  - The sound transmission loss (STL) of a test sample measured in sound transmission
      facilities is affected by the opening in which it is located. This is called the
      niche effect. This paper uses a modal approach to study the STL of a rectangular
      plate with or without an attached porous material located inside a box-shaped
      niche. The porous material is modeled as a limp equivalent fluid. The proposed
      model is validated by comparison with finite element/boundary element
      computations. Using a condensation of the pressure fields in the niche, the niche
      effect is interpreted in terms of a modification of the modal blocked pressure
      fields acting on the panel induced by the front cavity and by a modification of
      the radiation efficiency of the panel modes due to the presence of the back
      cavity. The modal approach is then used to investigate the impact of (1) the
      presence of a porous material attached to the panel on the niche effect and (2)
      the niche effect on the assessment of the porous material insertion loss. A
      simplified model for the porous material based on a transfer matrix approach is
      also proposed to predict the STL of the system and its validity is discussed. 

PMID- 25618045
TI  - Equivalence of time and aperture domain additive noise in ultrasound coherence.
AB  - Ultrasonic echoes backscattered from diffuse media, recorded by an array
      transducer and appropriately focused, demonstrate coherence predicted by the van
      Cittert-Zernike theorem. Additive noise signals from off-axis scattering,
      reverberation, phase aberration, and electronic (thermal) noise can all
      superimpose incoherent or partially coherent signals onto the recorded echoes,
      altering the measured coherence. An expression is derived to describe the effect
      of uncorrelated random channel noise in terms of the noise-to-signal ratio.
      Equivalent descriptions are made in the aperture dimension to describe
      uncorrelated magnitude and phase apodizations of the array. Binary apodization is
      specifically described as an example of magnitude apodization and adjustments are
      presented to minimize the artifacts caused by finite signal length. The effects
      of additive noise are explored in short-lag spatial coherence imaging, an image
      formation technique that integrates the calculated coherence curve of acquired
      signals up to a small fraction of the array length for each lateral and axial
      location. A derivation of the expected contrast as a function of noise-to-signal
      ratio is provided and validation is performed in simulation. 

PMID- 25618046
TI  - Violin plate modes.
AB  - As the first step toward developing a generic model for the acoustically
      radiating vibrational modes of the violin and related instruments, the modes of
      both freely supported and edge-constrained top and back plates have been
      investigated as functions of shape, arching height, elastic anisotropy, the f
      holes and associated island area, thickness graduations, and the additional
      boundary constraints of the ribs, soundpost, and bass-bar present in the
      assembled instrument. Comsol shell structure finite element software has been
      used as a quasi-experimental tool, with physical and geometric properties varied
      smoothly, often over several orders of magnitude, allowing the development of the
      plate modes to be followed continuously from those of an initially square plate
      to those of doubly-arched, guitar-shaped, orthotropic plates and their dependence
      on all the above factors. 

PMID- 25618047
TI  - Sound propagation over soft ground without and with crops and potential for
      surface transport noise attenuation.
AB  - Growing demand on transportation, road, and railway networks has resulted in
      increased levels of annoyance from road traffic. Optimized use of green surfaces
      in combination with vegetation may be desirable as a method for reducing the
      noise impact of road traffic in urban and rural environments. Sound propagation
      over soft ground and through crops has been studied through outdoor measurements
      at short and medium ranges and through predictions. At lower frequencies, ground
      effect is dominant, and there is little or no attenuation due to crops. At higher
      frequencies above 3-4 kHz, the attenuation in crops is dominant. It was also
      found that the ground effects and the influence of crops can be treated
      independently and can be added to obtain the total effect. Sound attenuation by
      crops is the result of multiple scattering between the stems and leaves, loss of
      coherence, and viscous and thermal losses due to foliage. The major contribution
      is associated with viscous and thermal losses. A model for sound attenuation by
      vegetation is proposed. Insertion losses for a typical road traffic noise source
      have been calculated that result either by replacing hard ground with different
      types of acoustically soft ground or by growing crops along the road sides. 

PMID- 25618048
TI  - Longitudinal annoyance responses to a road traffic noise management strategy that
      reduced heavy vehicles at night.
AB  - A traffic management strategy was designed to reduce trucks using an urban
      corridor. The intervention had potential to affect night-time truck flows, but
      did not target truck traffic in the day, or vehicles other than trucks at any
      hour. A two-year long panel study measured the community's response to this
      intervention, using five repeated measurements of response. There were
      significant reductions in the panel's response to noise, both for night-time
      annoyance and for interference with activities. This was remarkable given that
      noise monitoring showed that the intervention produced no change in conventional
      traffic noise indicators. However, there were measureable changes in the number
      of articulated truck movements at night, and the benefit can be attributed to
      reduction in the number of noise events from heavy vehicles. The parallel
      tracking of changes in reported noise effects and the numbers of heavy vehicles
      in the night hours in this longitudinal study provides strong support to the
      notion that noise effects at night depend on the number of noise events
      experienced, not only on the overall level of traffic noise. The latter appear to
      be unresponsive indicators by which to assess the noise-effect benefit of heavy
      vehicle reduction strategies. 

PMID- 25618049
TI  - A survey of acoustic conditions and noise levels in secondary school classrooms
      in England.
AB  - An acoustic survey of secondary schools in England has been undertaken. Room
      acoustic parameters and background noise levels were measured in 185 unoccupied
      spaces in 13 schools to provide information on the typical acoustic environment
      of secondary schools. The unoccupied acoustic and noise data were correlated with
      various physical characteristics of the spaces. Room height and the amount of
      glazing were related to the unoccupied reverberation time and therefore need to
      be controlled to reduce reverberation to suitable levels for teaching and
      learning. Further analysis of the unoccupied data showed that the introduction of
      legislation relating to school acoustics in England and Wales in 2003
      approximately doubled the number of school spaces complying with current
      standards. Noise levels were also measured during 274 lessons to examine typical
      levels generated during teaching activities in secondary schools and to
      investigate the influence of acoustic design on working noise levels in the
      classroom. Comparison of unoccupied and occupied data showed that unoccupied
      acoustic conditions affect the noise levels occurring during lessons. They were
      also related to the time spent in disruption to the lessons (e.g., students
      talking or shouting) and so may also have an impact upon student behavior in the
      classroom. 

PMID- 25618051
TI  - Optimal virtual mechanical impedances for the vibroacoustic active control of a
      thin plate.
AB  - In order to reduce the acoustic power radiated by a flexible panel, dual
      colocated actuator / sensor pairs are used to modify its vibration. The control
      strategy implemented for harmonic disturbances leads to locally impose a virtual
      mechanical impedance to the structure, using the linear relation between the
      actuator input and the control output of each pair. This virtual mechanical
      impedance is computed in order to minimize the radiated acoustic power. The
      proposed approach consists in two steps: (1) the matrix of optimal virtual
      mechanical impedance is calculated by measuring the primary disturbance and the
      transfer functions between actuators and structural/acoustic sensors and (2) the
      virtual mechanical impedance objective is achieved using a real-time integral
      controller. It is shown that such an optimal control approach leads to better
      sound power reduction than a classical active damping strategy where the virtual
      mechanical impedance is defined as real positive. Theoretical and experimental
      results are compared, also showing that the method proposed here is robust
      regarding variations of the primary disturbance. 

PMID- 25618050
TI  - The subjective effect of low frequency content in road traffic noise.
AB  - Based on subjective listening trials, Torija and Flindell [J. Acoust. Soc. Am.
      135, 1-4 (2014)] observed that low frequency content in typical urban main road
      traffic noise appeared to make a smaller contribution to reported annoyance than
      might be inferred from its objective or physical dominance. This paper reports a
      more detailed study which was aimed at (i) identifying the difference in sound
      levels at which low frequency content becomes subjectively dominant over mid and
      high frequency content and (ii) investigating the relationship between loudness
      and annoyance under conditions where low frequency content is relatively more
      dominant, such as indoors where mid and high frequency content is reduced. The
      results suggested that differences of at least +30 dB between the low frequency
      and the mid/high frequency content are needed for changes in low frequency
      content to have as much subjective effect as equivalent changes in mid and high
      frequency content. This suggests that common criticisms of the A-frequency
      weighting based on a hypothesized excessive downweighting of the low frequency
      content may be relatively unfounded in this application area.

PMID- 25618052
TI  - Describing and classifying urban sound environments with a relevant set of
      physical indicators.
AB  - Categorization is a powerful method for describing urban sound environments.
      However, it has only been applied, until now, to discrete noise data collection,
      whereas sound environments vary continuously both in space and time. Therefore, a
      procedure is developed in this paper for describing the variations of urban sound
      environments. The procedure consists of mobile measurements, followed by a
      statistical clustering analysis that selects relevant noise indicators and
      classifies sound environments. Analysis are based on a 3 days + 1 night survey
      where geo-referenced noise measurements were collected over 19 1-h soundwalk
      periods in a district of Marseille, France. The clustering analysis showed that a
      limited subset of indicators is sufficient to discriminate sound environments.
      The three indicators that emerged from the clustering, namely, the Leq, A, the
      standard deviation sigmaL eq, A, and the sound gravity spectrum SGC[50 Hz-10
      kHz], are consistent with previous studies on sound environment classification.
      Moreover, the procedure proposed enables the description of the sound
      environment, which is classified into homogenous sound environment classes by
      means of the selected indicators. Thus, the procedure can be adapted to any urban
      environment, and can, for instance, favorably enhance perceptive studies by
      delimiting precisely the spatial extent of each typical sound environment.

PMID- 25618053
TI  - Optically excited nanoscale ultrasonic transducers.
AB  - In order to work at higher ultrasonic frequencies, for instance, to increase the
      resolution, it is necessary to fabricate smaller and higher frequency
      transducers. This paper presents an ultrasonic transducer capable of being made
      at a very small size and operated at GHz frequencies. The transducers are
      activated and read optically using pulsed lasers and without physical contact
      between the instrumentation and the transducer. This removes some of the
      practical impediments of traditional piezoelectric architectures (such as wiring)
      and allows the devices to be placed immediately on or within samples, reducing
      the significant effect of attenuation which is very strong at frequencies above 1
      GHz. The transducers presented in this paper exploit simultaneous optical and
      mechanical resonances to couple the optical input into ultrasonic waves and vice
      versa. This paper discusses the mechanical and optical design of the devices at a
      modest scale (a few MUm) and explores the scaling of the transducers toward the
      sub-micron scale. Results are presented that show how the transducers response
      changes depending on its local environment and how the resonant frequency shifts
      when the transducer is loaded by a printed protein sample.

PMID- 25618054
TI  - Subharmonic tonal noise from backflow vortices radiated by a low-speed ring fan
      in uniform inlet flow.
AB  - In order to highlight the mechanisms responsible for subharmonic tonal noise, a
      complete aeroacoustic study of a ring fan in presence of a uniform inlet flow is
      conducted. Unsteady RANS simulations with a compressible flow solver are used to
      compute the flow field and identify the acoustic sources on the rotor. The tip
      clearance recirculation shows upstream vortices that impinge the rotor blades and
      create the main source of unsteadiness on the fan. Since these vortices rotate at
      a lower speed than the rotor, the frequency of the impact is lower than the blade
      passing frequency. The acoustic signature is computed by propagating the noise
      sources located on the rotor surfaces using two methods: A Ffowcs-Williams and
      Hawkings analogy in the time-domain and an analytical model in the frequency
      domain based on the compact rotating dipole formulation. A comparison with
      experimental results confirms that the aeroacoustic phenomena responsible for the
      subharmonic tonal noise are well captured and properly propagated by the acoustic
      codes. 

PMID- 25618055
TI  - In-plane time-harmonic elastic wave motion and resonance phenomena in a layered
      phononic crystal with periodic cracks.
AB  - This paper presents an elastodynamic analysis of two-dimensional time-harmonic
      elastic wave propagation in periodically multilayered elastic composites, which
      are also frequently referred to as one-dimensional phononic crystals, with a
      periodic array of strip-like interior or interface cracks. The transfer matrix
      method and the boundary integral equation method in conjunction with the Bloch
      Floquet theorem are applied to compute the elastic wave fields in the layered
      periodic composites. The effects of the crack size, spacing, and location, as
      well as the incidence angle and the type of incident elastic waves on the wave
      propagation characteristics in the composite structure are investigated in
      details. In particular, the band-gaps, the localization and the resonances of
      elastic waves are revealed by numerical examples. In order to understand better
      the wave propagation phenomena in layered phononic crystals with distributed
      cracks, the energy flow vector of Umov and the corresponding energy streamlines
      are visualized and analyzed. The numerical results demonstrate that large energy
      vortices obstruct elastic wave propagation in layered phononic crystals at
      resonance frequencies. They occur before the cracks reflecting most of the energy
      transmitted by the incoming wave and disappear when the problem parameters are
      shifted from the resonant ones. 

PMID- 25618056
TI  - Aeroacoustic response of coaxial wall-mounted Helmholtz resonators in a low-speed
      wind tunnel.
AB  - The aeroacoustic response of coaxial wall-mounted Helmholtz resonators with
      different neck geometries in a low-speed wind tunnel has been investigated.
      Experimental test results of this system reveal a strong aeroacoustic response
      over a Strouhal number range of 0.25 to 0.1 for both increasing and decreasing
      the flow rate in the wind tunnel. Aeroacoustic response in the low-amplitude
      range O(10(-3)) < Vac/Vflow < O(10(-1)) has been successfully modeled by
      describing-function analysis. This analysis, coupled with a turbulent flow
      velocity distribution model, gives reasonable values for the location in the flow
      of the undulating stream velocity that drives vortex shedding at the resonator
      mouth. Having an estimate for the stream velocity that drives the flow-excited
      resonance is crucial when employing the describing-function analysis to predict
      aeroacoustic response of resonators.

PMID- 25618057
TI  - Ultrasonic reflectometry in air: errors of sample positioning.
AB  - The reflection coefficient of ultrasonic waves propagating in air and interacting
      with a plane surface of a solid is considered. The simulation of dependence of
      the reflection coefficient on errors of sample positioning is performed using a
      finite beam model along with an angular spectrum method, and next the results are
      validated experimentally. The simulations show that for the considered range of
      geometrical parameters, the role of the wave divergence for the reflection
      coefficient in air is insignificant. The important consequences of errors of the
      sample positioning are that the shift of the sample influences mostly the phase,
      while the errors of inclination of the sample mainly affect the magnitude of the
      reflection coefficient. The experiments confirm simulation results pointing out
      the necessity of high precision of measurements for ultrasonic reflectometry in
      air. The results can be used for assessment of precision, calibration, and
      reduction of errors in applications of the reflectometry tests. 

PMID- 25618058
TI  - Enhancing the absorption properties of acoustic porous plates by periodically
      embedding Helmholtz resonators.
AB  - This paper studies the acoustical properties of hard-backed porous layers with
      periodically embedded air filled Helmholtz resonators. It is demonstrated that
      some enhancements in the acoustic absorption coefficient can be achieved in the
      viscous and inertial regimes at wavelengths much larger than the layer thickness.
      This enhancement is attributed to the excitation of two specific modes: Helmholtz
      resonance in the viscous regime and a trapped mode in the inertial regime. The
      enhancement in the absorption that is attributed to the Helmholtz resonance can
      be further improved when a small amount of porous material is removed from the
      resonator necks. In this way the frequency range in which these porous materials
      exhibit high values of the absorption coefficient can be extended by using
      Helmholtz resonators with a range of carefully tuned neck lengths. 

PMID- 25618059
TI  - Mixing of two co-directional Rayleigh surface waves in a nonlinear elastic
      material.
AB  - The mixing of two co-directional, initially monochromatic Rayleigh surface waves
      in an isotropic, homogeneous, and nonlinear elastic solid is investigated using
      analytical, finite element method, and experimental approaches. The analytical
      investigations show that while the horizontal velocity component can form a shock
      wave, the vertical velocity component can form a pulse independent of the
      specific ratios of the fundamental frequencies and amplitudes that are mixed.
      This analytical model is then used to simulate the development of the
      fundamentals, second harmonics, and the sum and difference frequency components
      over the propagation distance. The analytical model is further extended to
      include diffraction effects in the parabolic approximation. Finally, the
      frequency and amplitude ratios of the fundamentals are identified which provide
      maximum amplitudes of the second harmonics as well as of the sum and difference
      frequency components, to help guide effective material characterization; this
      approach should make it possible to measure the acoustic nonlinearity of a solid
      not only with the second harmonics, but also with the sum and difference
      frequency components. Results of the analytical investigations are then confirmed
      using the finite element method and the experimental feasibility of the proposed
      technique is validated for an aluminum specimen. 

PMID- 25618060
TI  - Scattering of flexural waves from a hole in a thin plate with an internal beam.
AB  - The scattering of flexural waves by a hole in a thin plate traversed by a beam is
      modeled here by coupling the Kirchhoff-Love and the Euler-Bernoulli theories. A
      closed form expression is obtained for the transfer matrix (T-matrix) relating
      the incident wave to the scattered cylindrical waves. For this purpose, a general
      method has been developed, based on an analogous impedance method for acoustic
      waves, for calculating the T-matrix for flexural wave scattering problems. The T
      matrix for the problem considered displays a simple structure, composed of
      distinct sub-matrices which decouple the inside and the outside fields. The
      conservation of energy principle and numerical comparisons with a commercial
      finite element simulator have been used to prove the theory. 

PMID- 25618061
TI  - Simulation of sound propagation over porous barriers of arbitrary shapes.
AB  - A time-domain solver using an immersed boundary method is investigated for
      simulating sound propagation over porous and rigid barriers of arbitrary shapes.
      In this study, acoustic propagation in the air from an impulse source over the
      ground is considered as a model problem. The linearized Euler equations are
      solved for sound propagation in the air and the Zwikker-Kosten equations for
      propagation in barriers as well as in the ground. In comparison to the analytical
      solutions, the numerical scheme is validated for the cases of a single rigid
      barrier with different shapes and for two rigid triangular barriers. Sound
      propagations around barriers with different porous materials are then simulated
      and discussed. The results show that the simulation is able to capture the sound
      propagation behaviors accurately around both rigid and porous barriers. 

PMID- 25618062
TI  - Three-dimensional parabolic equation model for low frequency sound propagation in
      irregular urban canyons.
AB  - A three-dimensional wide-angle parabolic equation (3DPE) is used to model low
      frequency sound propagation in irregular urban canyons at low computational cost.
      This one-way wave equation is solved using the Alternating Direction Implicit
      method. A finite difference scheme adapted to the geometry of the urban
      environment is then developed. Abrupt variations of the street width are treated
      as a single scattering problem using the Kirchhoff approximation. Numerical
      results are compared with experimental data obtained on a scale model of a
      street. Comparisons show the ability of the 3DPE model to provide reliable
      transmitted fields even for large irregularities. 

PMID- 25618063
TI  - Contribution of double scattering in diffuse ultrasonic backscatter measurements.
AB  - Diffuse ultrasonic backscatter measurements are used to describe the effective
      grain scattering present during high frequency ultrasonic inspections. Accurate
      modeling of the backscatter is important for both flaw detection and
      microstructural characterization. Previous models have been derived under the
      assumption of single scattering for which the ultrasound is assumed to scatter
      only once in the time between excitation and detection. This assumption has been
      shown to be valid in many experiments for which the time scales are short or the
      frequency is sufficiently low. However, there are also many instances (e.g., for
      strongly scattering materials, unfocused beams, or long propagation paths) for
      which the single scattering assumption appears to break down. In this article, a
      model for the double scatter is developed within the previous formalism based on
      Wigner distribution functions. The final expression allows the effect of double
      scattering to be estimated for any combination of experimental parameters. The
      improved proposed model is anticipated to increase the capabilities of ultrasonic
      microstructural evaluation, especially in terms of probability of detection
      estimates. 

PMID- 25618065
TI  - A spatial compression technique for head-related transfer function interpolation
      and complexity estimation.
AB  - A head-related transfer function (HRTF) model employing Legendre polynomials
      (LPs) is evaluated as an HRTF spatial complexity indicator and interpolation
      technique in the azimuth plane. LPs are a set of orthogonal functions derived on
      the sphere which can be used to compress an HRTF dataset by transforming it into
      a lower dimensional space. The LP compression technique was applied to various
      HRTF datasets, both real and synthetic, to determine how much different HRTFs can
      be compressed with respect to their structural complexity and their spatial
      resolution. The spatial complexity of different datasets was evaluated
      quantitatively by defining an HRTF spatial complexity index, which considers the
      rate of change in HRTF power spectrum with respect to spatial position. The
      results indicate that the compression realized by the LP technique is largely
      independent of the number of spatial samples in the HRTF dataset, while
      compressibility tracks the HRTF spatial complexity index so that more LP
      coefficients are needed to represent an HRTF dataset with a larger complexity
      index. The slope of the complexity index with respect to sub-sampling density can
      be used as a predictor for high interpolation error. 

PMID- 25618064
TI  - Sensitivity to interaural envelope correlation changes in bilateral cochlear
      implant users.
AB  - Provision of bilateral cochlear implants (CIs) to people who are deaf is
      partially justified by improved abilities to understand speech in noise when
      comparing bilateral vs unilateral listening conditions. However, bilateral CI
      listeners generally show only monaural head shadow with little improvement in
      speech understanding due to binaural unmasking. Sensitivity to change in
      interaural envelope correlation, which is related to binaural speech unmasking,
      was investigated. Bilateral CI users were tested with bilaterally synchronized
      processors at single, pitch-matched electrode pairs. First, binaural masking
      level differences (BMLDs) were measured using 1000 pulse-per-second (pps)
      carriers, yielding BMLDs of 11.1 +/- 6.5 and 8.5 +/- 4.2 dB for 10- and 50-Hz
      bandwidth masking noises, respectively. Second, envelope correlation change just
      noticeable differences (JNDs) were measured. Stimuli presented at 1000 pps
      yielded lower JNDs than those presented at 100 pps. Furthermore, perfectly
      correlated reference stimuli produced lower JNDs than uncorrelated references,
      and uncorrelated references generally produced immeasurable JNDs. About 25% of
      JNDs measured in the CI listeners were in the range of JNDs observed in normal
      hearing listeners presented CI simulations. In conclusion, CI listeners can
      perceive changes in interaural envelope correlation, but the poor performance may
      be a major limiting factor in binaural unmasking tested to date in realistic
      listening environments.

PMID- 25618066
TI  - Audio-visual speech scene analysis: characterization of the dynamics of unbinding
      and rebinding the McGurk effect.
AB  - While audiovisual interactions in speech perception have long been considered as
      automatic, recent data suggest that this is not the case. In a previous study,
      Nahorna et al. [(2012). J. Acoust. Soc. Am. 132, 1061-1077] showed that the
      McGurk effect is reduced by a previous incoherent audiovisual context. This was
      interpreted as showing the existence of an audiovisual binding stage controlling
      the fusion process. Incoherence would produce unbinding and decrease the weight
      of the visual input in fusion. The present paper explores the audiovisual binding
      system to characterize its dynamics. A first experiment assesses the dynamics of
      unbinding, and shows that it is rapid: An incoherent context less than 0.5 s long
      (typically one syllable) suffices to produce a maximal reduction in the McGurk
      effect. A second experiment tests the rebinding process, by presenting a short
      period of either coherent material or silence after the incoherent unbinding
      context. Coherence provides rebinding, with a recovery of the McGurk effect,
      while silence provides no rebinding and hence freezes the unbinding process.
      These experiments are interpreted in the framework of an audiovisual speech scene
      analysis process assessing the perceptual organization of an audiovisual speech
      input before decision takes place at a higher processing stage. 

PMID- 25618069
TI  - Articulatory reduction and coarticulation in Catalan three-consonant sequences.
AB  - Electropalatographic and acoustic data on Catalan /Ck#C/ sequences where # is a
      word boundary and /k/ is preceded by /l, s, r/ and followed by /b, m, d, l, n, z,
      r, y/ were collected in order to test the hypothesis that the velar stop is most
      prone to be reduced and deleted next to consonants involving high articulatory
      and aerodynamic demands. Analysis results reveal the absence of a velar stop
      closure in about half of the sequence tokens, mostly so when /k/ occurs after /s/
      and before an oral stop presumably due to the high manner of articulation
      requirements involved. On the other hand, /Ck#C/ sequences where a /k/ closure
      period is available show a prominent realization of the velar stop mostly next to
      /s, z/. This scenario points to two different production mechanisms for three
      consonant sequences with contextual obstruents: articulatory reduction and
      elision, and a slowing down and an increase in articulatory salience, of the
      velar stop. /Ck#C/ sequences lacking an acoustic closure for /k/ were found to
      show a residual velar stop articulation which was implemented through an increase
      in cluster duration and in dorsopalatal contact at the approximate /k/ location
      in comparison to identical /C#C/ sequences with no /k/. 

PMID- 25618067
TI  - Musicians and non-musicians are equally adept at perceiving masked speech.
AB  - There is much interest in the idea that musicians perform better than non
      musicians in understanding speech in background noise. Research in this area has
      often used energetic maskers, which have their effects primarily at the auditory
      periphery. However, masking interference can also occur at more central auditory
      levels, known as informational masking. This experiment extends existing research
      by using multiple maskers that vary in their informational content and similarity
      to speech, in order to examine differences in perception of masked speech between
      trained musicians (n = 25) and non-musicians (n = 25). Although musicians
      outperformed non-musicians on a measure of frequency discrimination, they showed
      no advantage in perceiving masked speech. Further analysis revealed that non
      verbal IQ, rather than musicianship, significantly predicted speech reception
      thresholds in noise. The results strongly suggest that the contribution of
      general cognitive abilities needs to be taken into account in any investigations
      of individual variability for perceiving speech in noise.

PMID- 25618068
TI  - Age effects in discrimination of intervals within rhythmic tone sequences.
AB  - This study measured listener sensitivity to increments of a target inter-onset
      interval (IOI) embedded within tone sequences that featured different rhythmic
      patterns. The sequences consisted of six 50-ms 1000-Hz tone bursts separated by
      silent intervals that were adjusted to create different timing patterns. Control
      sequences were isochronous, with all tonal IOIs fixed at either 200 or 400 ms,
      while other patterns featured combinations of the two IOIs arranged to create
      different sequential tonal groupings. Duration difference limens in milliseconds
      for increments of a single sequence IOI were measured adaptively by adjusting the
      duration of an inter-tone silent interval. Specific target IOIs within sequences
      differed across discrimination conditions. Listeners included younger normal
      hearing adults and groups of older adults with and without hearing loss.
      Discrimination performance measured for each of the older groups of listeners was
      observed to be equivalent, with each group exhibiting significantly poorer
      discrimination performance than the younger listeners in each sequence condition.
      Additionally, the specific influence of variable rhythmic grouping on temporal
      sensitivity was found to be greatest among older listeners.

PMID- 25618070
TI  - The softest sound levels of the human voice in normal subjects.
AB  - Accurate measurement of the softest sound levels of phonation presents technical
      and methodological challenges. This study aimed at (1) reliably obtaining
      normative data on sustained softest sound levels for the vowel [a:] at
      comfortable pitch; (2) comparing the results for different frequency and time
      weighting methods; and (3) refining the Union of European Phoniatricians'
      recommendation on allowed background noise levels for scientific and equipment
      manufacturers' purposes. Eighty healthy untrained participants (40 females, 40
      males) were investigated in quiet rooms using a head-mounted microphone and a
      sound level meter at 30 cm distance. The one-second-equivalent sound levels were
      more stable and more representative for evaluating the softest sustained
      phonations than the fast-time-weighted levels. At 30 cm, these levels were in the
      range of 48-61 dB(C)/41-53 dB(A) for females and 49 - 64 dB(C)/35-53 dB(A) for
      males (5% to 95% quantile range). These ranges may serve as reference data in
      evaluating vocal normality. In order to reach a signal-to-noise ratio of at least
      10 dB for more than 95% of the normal population, the background noise should be
      below 25 dB(A) and 38 dB(C), respectively, for the softest phonation measurements
      at 30 cm distance. For the A-weighting, this is 15 dB lower than the previously
      recommended value.

PMID- 25618072
TI  - Reduction of non-native accents through statistical parametric articulatory
      synthesis.
AB  - This paper presents an articulatory synthesis method to transform utterances from
      a second language (L2) learner to appear as if they had been produced by the same
      speaker but with a native (L1) accent. The approach consists of building a
      probabilistic articulatory synthesizer (a mapping from articulators to acoustics)
      for the L2 speaker, then driving the model with articulatory gestures from a
      reference L1 speaker. To account for differences in the vocal tract of the two
      speakers, a Procrustes transform is used to bring their articulatory spaces into
      registration. In a series of listening tests, accent conversions were rated as
      being more intelligible and less accented than L2 utterances while preserving the
      voice identity of the L2 speaker. No significant effect was found between the
      intelligibility of accent-converted utterances and the proportion of phones
      outside the L2 inventory. Because the latter is a strong predictor of
      pronunciation variability in L2 speech, these results suggest that articulatory
      resynthesis can decouple those aspects of an utterance that are due to the
      speaker's physiology from those that are due to their linguistic gestures. 

PMID- 25618073
TI  - Numerical analysis of the vibroacoustic properties of plates with embedded grids
      of acoustic black holes.
AB  - The concept of an Acoustic Black Hole (ABH) has been developed and exploited as
      an approach for passively attenuating structural vibration. The basic principle
      of the ABH relies on proper tailoring of the structure geometrical properties in
      order to produce a gradual reduction of the flexural wave speed, theoretically
      approaching zero. For practical systems the idealized "zero" wave speed condition
      cannot be achieved so the structural areas of low wave speed are treated with
      surface damping layers to allow the ABH to approach the idealized dissipation
      level. In this work, an investigation was conducted to assess the effects that
      distributions of ABHs embedded in plate-like structures have on both vibration
      and structure radiated sound, focusing on characterizing and improving low
      frequency performance. Finite Element and Boundary Element models were used to
      assess the vibration response and radiated sound power performance of several
      plate configurations, comparing baseline uniform plates with embedded periodic
      ABH designs. The computed modal loss factors showed the importance of the ABH
      unit cell low order modes in the overall vibration reduction effectiveness of the
      embedded ABH plates at low frequencies where the free plate bending wavelengths
      are longer than the scale of the ABH. 

PMID- 25618071
TI  - The impact of musical training and tone language experience on talker
      identification.
AB  - Listeners can use pitch changes in speech to identify talkers. Individuals
      exhibit large variability in sensitivity to pitch and in accuracy perceiving
      talker identity. In particular, people who have musical training or long-term
      tone language use are found to have enhanced pitch perception. In the present
      study, the influence of pitch experience on talker identification was
      investigated as listeners identified talkers in native language as well as non
      native languages. Experiment 1 was designed to explore the influence of pitch
      experience on talker identification in two groups of individuals with potential
      advantages for pitch processing: musicians and tone language speakers. Experiment
      2 further investigated individual differences in pitch processing and the
      contribution to talker identification by testing a mediation model. Cumulatively,
      the results suggested that (a) musical training confers an advantage for talker
      identification, supporting a shared resources hypothesis regarding music and
      language and (b) linguistic use of lexical tones also increases accuracy in
      hearing talker identity. Importantly, these two types of hearing experience
      enhance talker identification by sharpening pitch perception skills in a domain
      general manner. 

PMID- 25618074
TI  - Active control of sound transmission through a rectangular panel using point
      force actuators and piezoelectric film sensors.
AB  - This study deals with the active control of sound transmission through a
      rectangular panel, based on single input, single output feedforward vibration
      control using point-force actuators and piezoelectric film sensors. It focuses on
      the phenomenon in which the sound power transmitted through a finite-sized panel
      drops significantly at some frequencies just below the resonance frequencies of
      the panel in the low-frequency range as a result of modal coupling cancellation.
      In a previous study, it was shown that when point-force actuators are located on
      nodal lines for the frequency at which this phenomenon occurs, a force equivalent
      to the incident sound wave can act on the panel. In this study, a practical
      method for sensing volume velocity using a small number of piezoelectric film
      strips is investigated. It is found that two quadratically shaped piezoelectric
      film strips, attached at the same nodal lines as those where the actuators were
      placed, can sense the volume velocity approximately in the low-frequency range.
      Results of simulations show that combining the proposed actuation method and the
      sensing method can achieve a practical control effect at low frequencies over a
      wide frequency range. Finally, experiments are carried out to demonstrate the
      validity and feasibility of the proposed method. 

PMID- 25618075
TI  - High frequency backscattering by a solid cylinder with axis tilted relative to a
      nearby horizontal surface.
AB  - The backscattering spectrum versus azimuthal angle, also called the "acoustic
      color" or "acoustic template," of solid cylinders located in the free water
      column have been previously studied. For cylinders lying proud on horizontal sand
      sediment, there has been progress in understanding the backscattering spectrum as
      a function of grazing angle and the viewing angle relative to the cylinder's
      axis. Significant changes in the proud backscattering spectrum versus the
      freefield case are associated with the interference of several multipaths
      involving the target and the surface. If the cylinder's axis has a vertical tilt
      such that one end is partially buried in the sand, the multipath structure is
      changed, thus modifying the resulting spectrum. Some of the changes in the
      template can be approximately modeled using a combination of geometrical and
      physical acoustics. The resulting analysis gives a simple approximation relating
      certain changes in the template with the vertical tilt of the cylinder. This
      includes a splitting in the azimuthal angle at which broadside multipath features
      are observed. A similar approximation also applies to a metallic cylinder
      adjacent to a flat free surface and was confirmed in tank experiments. 

PMID- 25618076
TI  - High-resolution bottom-loss estimation using the ambient-noise vertical coherence
      function.
AB  - The seabed reflection loss (shortly "bottom loss") is an important quantity for
      predicting transmission loss in the ocean. A recent passive technique for
      estimating the bottom loss as a function of frequency and grazing angle exploits
      marine ambient noise (originating at the surface from breaking waves, wind, and
      rain) as an acoustic source. Conventional beamforming of the noise field at a
      vertical line array of hydrophones is a fundamental step in this technique, and
      the beamformer resolution in grazing angle affects the quality of the estimated
      bottom loss. Implementation of this technique with short arrays can be hindered
      by their inherently poor angular resolution. This paper presents a derivation of
      the bottom reflection coefficient from the ambient-noise spatial coherence
      function, and a technique based on this derivation for obtaining higher angular
      resolution bottom-loss estimates. The technique, which exploits the (approximate)
      spatial stationarity of the ambient-noise spatial coherence function, is
      demonstrated on both simulated and experimental data. 

PMID- 25618077
TI  - Treatment of a sloping fluid-solid interface and sediment layering with the
      seismo-acoustic parabolic equation.
AB  - The parabolic equation method is extended to handle problems in seismo-acoustics
      that have multiple fluid and solid layers, continuous depth dependence within
      layers, and sloping interfaces between layers. The medium is approximated in
      terms of a series of range-independent regions, and a single-scattering
      approximation is used to compute transmitted fields across the vertical
      interfaces between regions. The approach is implemented in terms of a set of
      dependent variables that is well suited to piecewise continuous depth dependence
      in the elastic parameters, but one of the fluid-solid interface conditions in
      that formulation involves a second derivative that complicates the treatment of
      sloping interfaces. This issue is resolved by using a non-centered, four-point
      difference formula for the second derivative. The approach is implemented using a
      matrix decomposition that is efficient when the parameters of the medium have a
      general dependence within the upper layers of the sediment but only depend on
      depth in the water column and deep within the sediment. 

PMID- 25618078
TI  - Extraction of plate bending stiffness from coincidence angles of sound
      transmission measurements.
AB  - The bending stiffness in a homogeneous, isotropic, thin plate is experimentally
      derived from measurements of coincidence angles extracted from supercritical
      sound transmission versus frequency measurements. A computer controlled turn
      table rotates a plate sample and a receiver array, placed in the near field of
      the plate. The array is used to track the transmitted sound through the plate,
      generated by a far-field stationary source, using beam forming. The array
      technique enables measurement of plates measuring only one wavelength in width.
      Two examples are used for proof of concept, including an aluminum plate in air
      and an alumina plate under water. 

PMID- 25618079
TI  - Additional results for "joint entropy of continuously differentiable ultrasonic
      waveforms" [J. Acoust. Soc. Am. 133(1), 283-300 (2013)].
AB  - Previous results on the use of joint entropy for detection of targeted
      nanoparticles accumulating in the neovasculature of MDA435 tumors [Fig. 7 of M.
      S. Hughes et al., J. Acoust. Soc. Am. 133, 283-300 (2013)] are extended, with
      sensitivity improving by nearly another factor of 2. This result is obtained
      using a "quasi-optimal" reference waveform in the computation of the joint
      entropy imaging technique used to image the accumulating nanoparticles. 

PMID- 25618080
TI  - Sensitivity of odd-harmonic amplitudes to open quotient and skewing quotient in
      glottal airflow.
AB  - It is well known that a half-sinusoid has no odd harmonics other than the
      fundamental. If glottal flow in phonation were to approximate this exact
      waveshape, which is generally unlikely, some misperception of pitch and loss of
      vowel intelligibility would occur. The sensitivity of the glottal waveshape to
      this special shape is explored by systematically varying two parameters, open
      quotient and skewing quotient. Mild asymmetry (open quotient below 0.45 or above
      0.55 and/or skewing quotient greater than 2.0) equalizes the odd-even harmonic
      series. Singers and speakers avoid the exact symmetry by skewing the flow pulse
      with source-filter interaction. 

PMID- 25618081
TI  - The role of recovered envelope cues in the identification of temporal-fine
      structure speech for hearing-impaired listeners.
AB  - Narrowband speech can be separated into fast temporal cues [temporal fine
      structure (TFS)], and slow amplitude modulations (envelope). Speech processed to
      contain only TFS leads to envelope recovery through cochlear filtering, which has
      been suggested to account for TFS-speech intelligibility for normal-hearing
      listeners. Hearing-impaired listeners have deficits with TFS-speech
      identification, but the contribution of recovered-envelope cues to these deficits
      is unknown. This was assessed for hearing-impaired listeners by measuring
      identification of disyllables processed to contain TFS or recovered-envelope
      cues. Hearing-impaired listeners performed worse than normal-hearing listeners,
      but TFS-speech intelligibility was accounted for by recovered-envelope cues for
      both groups. 

PMID- 25618082
TI  - Acoustic behavior of porous ceiling absorbers based on local and extended
      reaction.
AB  - The acoustic behavior of ceiling absorbers can be predicted under different
      surface reaction assumptions: Local and extended reaction. This study aims to
      experimentally validate acoustic transfer functions near a ceiling absorber in an
      anechoic chamber based on the two surface reaction models. First, a ceiling
      absorber with two mounting conditions is modeled by equivalent fluid models, such
      as Delany-Bazley's, Miki's, and Komatsu's model, in various ways: (1) Local vs
      extended reaction and (2) plane-wave vs spherical-wave incidence. For a single
      absorber under anechoic conditions, the acoustic transfer functions for four
      source-receiver pairs are simulated using a pressure-based image source model,
      and then compared with measurements. For a rigid backing condition, both the
      local and extended reaction models agree well with the measurement. For an
      absorber backed by an air cavity, the extended reaction model agrees better at
      larger incidence angles at lower frequencies than the local reaction model.

PMID- 25618083
TI  - Erratum: Flow rate and duty cycle effects in lysis of Chlamydomonas reinhardtii
      using high-energy pulsed focused ultrasound [J. Acoust. Soc. Am. 135(6), 3632
      3638 (2014)].

PMID- 25618088
TI  - Dispersion curve recovery with orthogonal matching pursuit.
AB  - Dispersion curves characterize many propagation mediums. When known, many methods
      use these curves to analyze waves. Yet, in many scenarios, their exact values are
      unknown due to material and environmental uncertainty. This paper presents a fast
      implementation of sparse wavenumber analysis, a method for recovering dispersion
      curves from data. This approach, based on orthogonal matching pursuit, is
      compared with a prior implementation, based on basis pursuit denoising. In the
      results, orthogonal matching pursuit provides two to three orders of magnitude
      improvement in speed and a small average reduction in prediction capability. The
      analysis is demonstrated across multiple scenarios and parameters. 

PMID- 25618089
TI  - Propagation of time-reversed Lamb waves in bovine cortical bone in vitro.
AB  - The present study aims to investigate the propagation of time-reversed Lamb waves
      in bovine cortical bone in vitro. The time-reversed Lamb waves were successfully
      launched at 200 kHz in 18 bovine tibiae through a time reversal process of Lamb
      waves. The group velocities of the time-reversed Lamb waves in the bovine tibiae
      were measured using the axial transmission technique. They showed a significant
      correlation with the cortical thickness and tended to follow the theoretical
      group velocity of the lowest order antisymmetrical Lamb wave fairly well,
      consistent with the behavior of the slow guided wave in long cortical bones.

PMID- 25618090
TI  - Experimental characterization of vertical-axis wind turbine noise.
AB  - Vertical-axis wind turbines are wind-energy generators suitable for use in urban
      environments. Their associated noise thus needs to be characterized and
      understood. As a first step, this work investigates the relative importance of
      harmonic and broadband contributions via model-scale wind-tunnel experiments.
      Cross-spectra from a pair of flush-mounted wall microphones exhibit both
      components, but further analysis shows that the broadband dominates at
      frequencies corresponding to the audible range in full-scale operation. This
      observation has detrimental implications for noise-prediction reliability and
      hence also for acoustic design optimization. 

PMID- 25618091
TI  - Does restriction of pitch variation affect the perception of vocal emotions in
      Mandarin Chinese?
AB  - This study reports a finding about vocal expressions of emotion in Mandarin
      Chinese. Production and perception experiments used the same tone and mixed tone
      sequences to test whether pitch variation is restricted due to the presence of
      lexical tones. Results showed that the restriction of pitch variation occurred in
      all high level tone sequences (tone 1 group) with the expression of happiness but
      did not happen for other dynamic tone groups. However, perception analysis
      revealed that all the emotions in every tone group received high identification
      rates; this indicates that listeners used other cues for encoding happiness in
      the tone 1 group. This study demonstrates that the restriction of pitch variation
      does not affect the perception of vocal emotions. 

PMID- 25618092
TI  - Single-channel blind separation using L1-sparse complex non-negative matrix
      factorization for acoustic signals.
AB  - An innovative method of single-channel blind source separation is proposed. The
      proposed method is a complex-valued non-negative matrix factorization with
      probabilistically optimal L1-norm sparsity. This preserves the phase information
      of the source signals and enforces the inherent structures of the temporal codes
      to be optimally sparse, thus resulting in more meaningful parts factorization. An
      efficient algorithm with closed-form expression to compute the parameters of the
      model including the sparsity has been developed. Real-time acoustic mixtures
      recorded from a single-channel are used to verify the effectiveness of the
      proposed method. 

PMID- 25618093
TI  - High-frequency whistles of Guiana dolphins (Sotalia guianensis) in Guanabara Bay,
      southeastern Brazil.
AB  - Guiana dolphins produce whistles with a higher frequency and less complexity than
      most other delphinid species. The present study used a recording system with
      sampling rate of 192 kHz to describe the high-frequency whistles of Sotalia
      guianensis in Guanabara Bay, Rio de Janeiro. Eleven acoustic parameters (start,
      end, minimum, maximum, delta, center and peak frequency, duration, and frequency
      at 14, 12, and 34 of duration) were measured for all whistles. Whistles with a
      fundamental frequency up to 66.7 kHz were reported, thereby expanding the known
      frequency range of this species.

PMID- 25618094
TI  - Optimal integration of independent observations from Poisson sources.
AB  - The optimal integration of information from independent Poisson sources (such as
      neurons) was analyzed in the context of a two-interval, forced-choice detection
      task. When the mean count of the Poisson distribution is above 1, the benefit of
      integration is closely approximated by the predictions based on the square-root
      law of the Gaussian model. When the mean count falls far below 1, however, the
      benefit of integration clearly exceeds the predictions based on the square-root
      law. 

PMID- 25618095
TI  - Spectral loudness summation: shortcomings of current standards.
AB  - There are two competing national standards for the calculation of loudness of
      steady sounds, DIN 45631 and ANSI S3.4. Their different concepts of critical
      bands lead to different predictions for broadband sounds. As that discrepancy is
      neither constant nor linear but highly frequency-dependent, the present study
      investigates spectral loudness summation in three frequency regions, at various
      levels, and using two different methods. The results show that both algorithms
      overestimate loudness; however, DIN 45631 comes closer to the subjective
      evaluations and often falls within their interquartile range. The overestimation
      by the standards is particularly large in the frequency range from 2 to 5 kHz. 

PMID- 25618096
TI  - Laboratory measurements of high-frequency, acoustic broadband backscattering from
      sea ice and crude oil.
AB  - Recent decreases in summer sea ice cover are spurring interest in hydrocarbon
      extraction and shipping in Arctic waters, increasing the risk of an oil spill in
      ice covered waters. With advances in unmanned vehicle operation, there is an
      interest in identifying techniques for remote, underwater detection of oil spills
      from below. High-frequency (200-565 kHz), broadband acoustic scattering data
      demonstrate that oil can be detected and quantified under laboratory grown sea
      ice and may be of use in natural settings. A simple scattering model based on the
      reflection coefficients from the interfaces agrees well with the data. 

PMID- 25618097
TI  - Practical method for evaluating the sound field radiated from a waveguide.
AB  - This letter presents a simple and practical method for evaluating the sound field
      radiated from a waveguide. By using the proposed method, detailed information
      about the radiated sound field can be obtained by measuring the sound field in
      the mouth of the baffled waveguide. To examine this method's effectiveness, the
      radiated sound pressure distribution in space was first evaluated by using the
      proposed method, and then it was measured directly for comparison. Experiments
      using two different waveguides showed good agreement between the evaluated and
      the measured radiated sound pressure distributions. 

PMID- 25618098
TI  - Relationship between listeners' nonnative speech recognition and categorization
      abilities.
AB  - Enhancement of the perceptual encoding of talker characteristics (indexical
      information) in speech can facilitate listeners' recognition of linguistic
      content. The present study explored this indexical-linguistic relationship in
      nonnative speech processing by examining listeners' performance on two tasks:
      nonnative accent categorization and nonnative speech-in-noise recognition.
      Results indicated substantial variability across listeners in their performance
      on both the accent categorization and nonnative speech recognition tasks.
      Moreover, listeners' accent categorization performance correlated with their
      nonnative speech-in-noise recognition performance. These results suggest that
      having more robust indexical representations for nonnative accents may allow
      listeners to more accurately recognize the linguistic content of nonnative
      speech.

PMID- 25618099
TI  - Effect of stimulus bandwidth and duration on monaural envelope correlation
      perception.
AB  - Monaural envelope correlation perception is the ability to discriminate between
      stimuli composed of two or more bands of noise based on envelope correlation.
      Sensitivity decreases as stimulus bandwidth is reduced below 100 Hz. The present
      study manipulated stimulus bandwidth (25-100 Hz) and duration (25-800 ms) to
      evaluate whether performance of highly trained listeners is limited by the number
      of inherent modulation periods in each presentation. Stimuli were two bands of
      noise, separated by a 500-Hz gap centered on 2250 Hz. Performance improved
      reliably with increasing numbers of envelope modulation periods, although there
      were substantial individual differences.

PMID- 25618100
TI  - On distance dependence of pinna spectral patterns in head-related transfer
      functions.
AB  - The aim of this letter is to address a little understood question in sound source
      localization: Can the distance of a near sound source affect our own perception
      of its elevation? The issue is studied by means of an objective analysis of a
      database of distance-dependent head-related transfer functions (HRTFs) of a KEMAR
      (Knowles Electronic Manikin for Acoustic Research) mannequin with different
      pinnae on a dense spatial grid. Iso-directional HRTFs are compared through
      spectral error metrics; results indicate significant distance-dependent HRTF
      modifications due to the pinna occur when the source is close to the interaural
      axis. 

PMID- 25618101
TI  - Phoneme categorization relying solely on high-frequency energy.
AB  - Speech perception studies generally focus on the acoustic information present in
      the frequency regions below 6 kHz. Recent evidence suggests that there is
      perceptually relevant information in the higher frequencies, including
      information affecting speech intelligibility. This experiment examined whether
      listeners are able to accurately identify a subset of vowels and consonants in CV
      context when only high-frequency (above 5 kHz) acoustic information is available
      (through high-pass filtering and masking of lower frequency energy). The findings
      reveal that listeners are capable of extracting information from these higher
      frequency regions to accurately identify certain consonants and vowels. 

PMID- 25618102
TI  - Amplitude and phase equalization of stimuli for click evoked auditory brainstem
      responses.
AB  - Although auditory brainstem responses (ABRs), the sound-evoked brain activity in
      response to transient sounds, are routinely measured in humans and animals there
      are often differences in ABR waveform morphology across studies. One possible
      reason may be the method of stimulus calibration. To explore this hypothesis,
      click-evoked ABRs were measured from seven ears in four Mongolian gerbils
      (Meriones unguiculatus) using three common spectrum calibration strategies:
      Minimum phase filter, linear phase filter, and no filter. The results show
      significantly higher ABR amplitude and signal-to-noise ratio, and better waveform
      resolution with the minimum phase filtered click than with the other strategies. 

PMID- 25618104
TI  - A numerically stable formulation of the Green's function parabolic equation:
      Subtracting the surface-wave pole.
AB  - The original formulation of the Green's function parabolic equation (GFPE) can
      have numerical accuracy problems for large normalized surface impedances. To
      solve the accuracy problem, an improved form of the GFPE has been developed. The
      improved GFPE formulation is similar to the original formulation, but it has the
      surface-wave pole "subtracted." The improved GFPE is shown to be accurate for
      surface impedances varying over 2 orders of magnitude, with the largest having a
      magnitude exceeding 1000. Also, the improved formulation is slightly faster than
      the original formulation because the surface-wave component does not have to be
      computed separately. 

PMID- 25618103
TI  - Stimulus-frequency otoacoustic emissions in human newborns.
AB  - This study presents the first reported measurements of stimulus frequency
      emissions (SFOAEs) in 15 human newborns and compares their magnitudes and phase
      gradient delays to those reported in adults. SFOAEs in newborns were measured at
      stimulus levels as low as 15 dB sound pressure level (SPL). Responses were
      compared between adults and newborns at stimulus levels where SFOAEs in both age
      groups demonstrated approximately linear growth (<40 dB SPL for newborns, <25 dB
      SPL for adults). Neonates had adult-like SFOAE delays when compared in this
      fashion, which compensates for newborn middle ear inefficiencies.

PMID- 25618105
TI  - Method for generating realistic sound stimuli with given characteristics by
      controlled combination of audio recordings.
AB  - Audio recordings are often used to improve ecological validity of stimuli for
      laboratory research on effects of noise. In this paper a method is proposed for
      composing realistic environmental sound stimuli with (1) specified overall
      spectrum and (2) specified statistical distribution of sound event durations and
      semantic categories. The combination is addressed as a mixed integer linear
      programming problem. Objective measurements, for eight stimuli and a moderate
      size database, validate the method. The mean error in octave bands exposure level
      is 2.6 dB and the statistical distribution of sound event durations and semantic
      categories is perfectly matched.

PMID- 25618106
TI  - Overnight consolidation promotes generalization across talkers in the
      identification of nonnative speech sounds.
AB  - This investigation explored the generalization of phonetic learning across
      talkers following training on a nonnative (Hindi dental and retroflex) contrast.
      Participants were trained in two groups, either in the morning or in the evening.
      Discrimination and identification performance was assessed in the trained talker
      and an untrained talker three times over 24 h following training. Results suggest
      that overnight consolidation promotes generalization across talkers in
      identification, but not necessarily discrimination, of nonnative speech sounds.

PMID- 25618107
TI  - A free plate model can predict guided modes propagating in tubular bone-mimicking
      phantoms.
AB  - The goal of this work was to show that a non-absorbing free plate model can
      predict with a reasonable accuracy guided modes measured in bone-mimicking
      phantoms that have circular cross-section. Experiments were carried out on
      uncoated and coated phantoms using a clinical axial transmission setup.
      Adjustment of the plate model to the experimental data yielded estimates for the
      waveguide characteristics (thickness, bulk wave velocities). Fair agreement was
      achieved over a frequency range of 0.4 to 1.6 MHz. A lower accuracy observed for
      the thinnest bone-mimicking phantoms was caused by limitations in the wave number
      measurements rather than by the model itself.

PMID- 25618108
TI  - Effect of summer outdoor temperatures on work-related injuries in Quebec
      (Canada).
AB  - OBJECTIVE: To quantify the associations between occupational injury compensations
      and exposure to summer outdoor temperatures in Quebec (Canada). METHODS: The
      relationship between 374,078 injuries compensated by the Workers' Compensation
      Board (WCB) (between May and September, 2003-2010) and maximum daily outdoor
      temperatures was modelled using generalised linear models with negative binomial
      distributions. Pooled effect sizes for all 16 health regions of Quebec were
      estimated with random-effect models for meta-analyses for all compensations and
      by sex, age group, mechanism of injury, industrial sector and occupations (manual
      vs other) within each sector. Time lags and cumulative effect of temperatures
      were also explored. RESULTS: The relationship between daily counts of
      compensations and maximum daily temperatures reached statistical significance for
      three health regions. The incidence rate ratio (IRR) of daily compensations per 1
      degrees C increase was 1.002 (95% CI 1.002 to 1.003) for all health regions
      combined. Statistically significant positive associations were observed for men,
      workers aged less than 45 years, various industrial sectors with both indoor and
      outdoor activities, and for slips/trips/falls, contact with object/equipment and
      exposure to harmful substances/environment. Manual occupations were not
      systematically at higher risk than non-manual and mixed ones. CONCLUSIONS: This
      study is the first to quantify the association between work-related injury
      compensations and exposure to summer temperatures according to physical demands
      of the occupation and this warrants further investigations. In the context of
      global warming, results can be used to estimate future impacts of summer outdoor
      temperatures on workers, as well as to plan preventive interventions.

PMID- 25618109
TI  - New perspectives in the diagnostic of gingival recession.
AB  - Gingival recession (GR) is a common clinical situation observed in patient
      populations regardless of their age and ethnicity. It has been estimated that
      over 60% of the human population has gingival recession. It is the final effect
      of the interaction of multiple etiological factors. Identification and definition
      of the range of influence is often not possible, with the result that new methods
      for testing and elimination of potential etiological factors are still being
      sought. The aim of this study is to present the etiopathogenesis of gingival
      recessions with regard to the analysis of morphological and functional factors.
      For the assessment of the bone factors, we will describe the new cephalometric
      method for measuring sagital width of the bone in the central incisors area,
      places when GR are most commonly observed. Also, a review will be presented of
      modern methods of treatment; in particular classes recessions; usage substitute
      of autogenous tissue will be emphasized--collagen matrix, and primary culture
      fibroblasts on collagen net.

PMID- 25618110
TI  - ESBL-producing Escherichia coli isolated from bloodstream infections-
      antimicrobial susceptibility, conjugative transfer of resistance genes and
      phylogenetic origin.
AB  - BACKGROUND: The prevalence of bloodstream infections (BSIs) due to ESBL-producing
      Escherichia coli (ESBL-EC) strains has increased dramatically over the past
      years. OBJECTIVES: Characterization of ESBL-EC isolates collected from BSIs with
      regard to their antimicrobial susceptibility and phylogenetic background. The
      conjugative transfer of resistance determinants to the E. coli reference strain
      K12 C600 was also investigated. MATERIAL AND METHODS: A collection of forty-eight
      ESBL-EC strains recovered from BSIs was subjected to the study. These strains
      were obtained from the ICU (intensive care unit) of the Medical University
      Hospital, Wroclaw, Poland, during a four-year period (2009-2012). All the
      isolates were screened for ESBL production by the double disk synergy test
      (DDST). Transferability of plasmid-mediated resistance genes was performed by the
      conjugational broth method. Susceptibility to antibiotics and chemotherapeutics
      of clinical isolates and transconjugants was determined by the agar dilution
      method. PCR assay was used to detect the blaCTX-M gene in ESBL-EC tested and
      transconjugants. Affiliation to phylogenetic groups was done by the triplex PCR
      method. RESULTS: Conjugational transfer of plasmids responsible for ESBL to a
      recipient strain was successful for all the ESBL-EC analyzed (donors). The
      conjugation frequencies ranging from 2.3*10(-7) to 5.2*10(-1) per donor. In vitro
      susceptibility testing revealed that all the ESBL-EC isolates and their
      transconjugants were resistant to most of the antimicrobial agents tested with
      the exception of carbapenems, tigecycline, and beta-lactam-clavulanate
      combinations. Moreover, all the donor strains and their transconjugants were
      found to contain the blaCTX-M gene. The majority of the isolates analyzed
      belonged to phylogroups B2 (62.5%) and D (25%), whereas groups B1 and A were less
      frequently represented (8.3% and 4.2%, respectively). CONCLUSIONS: The results of
      the study confirm the need of antibiotic policies and effective infection control
      measures in hospital settings to minimize BSIs caused by multi-resistant ESBL
      producing pathogens.

PMID- 25618111
TI  - Bovine lactoferrin enhances proliferation of human peripheral blood lymphocytes
      and induces cytokine production in whole blood cultures.
AB  - BACKGROUND: Lactoferrin belongs to the immunoregulatory milk proteins involved in
      iron metabolism as well in providing innate immunity to newborns. The protein has
      been the subject of numerous clinical studies. OBJECTIVES: The aim of this
      investigation was to evaluate the effects of bovine lactoferrins (bLF), differing
      in source and iron content, on spontaneous proliferation of human peripheral
      blood mononuclear cells (PBMC) and cytokine production by human whole blood
      cultures. MATERIAL AND METHODS: The following bLF preparations were used:
      partially iron saturated or devoid of iron bLF from milk and bLF from colostrum.
      The study was conducted on 12 healthy volunteers (men, 20-24 years old). The
      effects of bLFs on the proliferation of PBMC in four-day cultures was studied at
      50-0.6 ug/mL concentration range and the rate of proliferation was determined
      using the MTT colorimetric method. TNF alpha and IL-6 levels, induced by the bLFs
      in 24 h whole blood cultures, were measured by ELISA. RESULTS: The lactoferrins
      stimulated autologous proliferation of human peripheral blood mononuclear cells
      (PBMC) in a dose-dependent manner, with a comparable efficacy. This stimulation
      occurred both in the constant presence of bLFs in the cultures and also upon
      preincubation of PBMC with bLFs with subsequent exhaustive wash of cells. Only
      bLF from colostrum induced production of tumor necrosis factor alpha (TNF-alpha)
      and interleukin-6 (IL-6) in cultures of whole blood cells. This phenomenon took
      place predominantly at concentration of 50 ug/mL. CONCLUSIONS: The results showed
      potent stimulation of the proliferative response of PBMC by bovine lactoferrin,
      associated with the induction of proinflammatory cytokines only in the case of
      colostral bLF. This observation may be of importance when high doses of bLF are
      used in therapy and by designing diet supplementation with this protein.

PMID- 25618112
TI  - Effect of different Bacillus Calmette-Guerin substrains on growth inhibition of
      T24 bladder cancer cells and cytokines secretion by BCG activated peripheral
      blood mononuclear cells of PBMCs.
AB  - BACKGROUND: Bladder carcinoma is the most common malignancy of the urinary tract.
      Approximately 75-85% of patients present non-muscle invasive bladder cancer
      (NMIBC). Standard primary treatment for NIMBC is transurethral resection (TUR)
      followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. BCG has
      been accepted as the most effective agent in clinical use against NMIBC. Various
      BCG substrains are used worldwide for bladder cancer immunotherapy although the
      impact of used BCG substrain on BCG antitumor capacity is a little investigated.
      OBJECTIVES: The aim of this study was to compare the antitumor capacity and the
      ability to trigger cytokines production of three BCG substrains by stimulation of
      the local innate immunity in vitro. MATERIAL AND METHODS: The human bladder
      cancer cell line T24 was co-cultured with each of the BCG substrains: Moreau,
      Tice and RIVM alone or with BCG pretreated DCs (dendric cells) and allogenic
      PBMCs derived from the same donor. The inhibition of T24 cell growth was
      evaluated by 3H-thymidine incorporation. Production of Th1 cytokines (IFN-gamma,
      TNF-alpha, IL-12) and Th2 cytokines (IL-10, IL-4) was measured in cultures of BCG
      activated PBMCs by ELISA test. RESULTS: An approximately two-fold inhibition of
      T24 cell proliferation was observed as a direct cytotoxic effect of tested BCG
      substrains on T24 cells. However, BCG inhibited the growth of tumor cells mainly
      by activating the effector cells of innate immunity. About a 10-fold inhibition
      of T24 cell proliferation was observed when T24 cells were co-cultured with
      allogenic BCG pretreated DCs and PBMCs derived from the same donor. The PBMCs
      activated by compared live BCG substrains secreted large amounts of TNF-alpha and
      IFN-gamma cytokines. CONCLUSIONS: Tested BCG substrains had little direct
      inhibitory effect on T24 cell proliferation. Moreau evolutionarily early BCG
      substrain showed similar strong, indirect antitumor effects as evolutionarily
      late BCG substrains Tice and RIVM.

PMID- 25618113
TI  - The effects of different intraabdominal pressure protocols in laparoscopic
      procedures on oxidative stress markers and morphology in rat ovaries.
AB  - BACKGROUND: To determine the effects of different intraabdominal pressure (IAP)
      on the ovaries in a laparoscopic rat model. OBJECTIVES: The aim of the study was
      to determine the effects on the ovaries of different intraabdominal pressures
      (IAP) in laparoscopic surgery in a rat model. MATERIAL AND METHODS: Thirty-two
      post-pubertal nonpregnant Sprague-Dawley rats were divided randomly into four
      groups. In the control group, no intraabdominal pressure (IAP) was applied. In
      Group Pp10 and Group Pp15, an IAP of 10 and 15 mm Hg, respectively, were applied
      by carbon dioxide insufflation for 60 min, and a 30-min desufflation was carried
      out. In Group IPp15, a 15 mm Hg IAP was applied for 10 min, and then CO2 was
      desufflated for 10 min. After this ischemic preconditioning, IAP was established
      at 15 mm Hg for 60 min, after which CO2 was desufflated for 30 min. Erythrocyte
      and ovarian tissue malondialdehyde (MDA) and histopathologic damage scores were
      evaluated. RESULTS: In Groups Pp10 and Pp15, ovarian tissue MDA values were
      significantly increased compared to the control group. In Groups Pp10 and Pp15,
      erythrocyte MDA values were significantly increased when compared to Group IPp15
      and the control group. Ovarian histopatological assesment scores were
      significantly higher in Group Pp15 than in Groups Pp10 and IPp15. CONCLUSIONS:
      Pneumoperitoneum causes injuries to abdominal organ such as the ovaries. The
      ischemic preconditioning method is more effective in reducing oxidative stress
      due to laparoscopic pneumoperitoneum than low-pressure pneumoperitoneum methods.

PMID- 25618114
TI  - BRAF overexpression induces rampant glioma proliferation independent of phospho
      EGFR expression.
AB  - BACKGROUND: The prognosis for gliomas is still dismal when treated with
      traditional approaches. Molecular targeted therapy has become a trend in treating
      tumors, including gliomas. However, molecular characteristics vary among
      different kinds of tumors and ethnic groups. OBJECTIVES: The aim of the research
      was to study the expression characteristics of key components in the EGFR pathway
      of gliomas in order to contribute new data for the molecular targeted treatment
      of gliomas. MATERIAL AND METHODS: EGFR, KRAS, BRAF, PI3K, phospho-EGFR and Ki67
      expression were detected with immunohistochemistry in 82 glioma specimens.
      RESULTS: The expression of EGFR was positively correlated with the patients' age.
      There were no significant differences in clinicopathological characteristics
      between gliomas with and without phospho-EGFR expression. EGFR overexpression was
      significantly correlated with phospho-EGFR expression. In gliomas with EGFR
      activation, overexpressions of EGFR, BRAF and PI3K were significantly correlated
      with proliferation. However, in gliomas without phospho-EGFR expression, only
      BRAF overexpression was significantly related to the proliferation of tumor
      cells. CONCLUSIONS: BRAF overexpression could be an independent factor causing
      tumorigenesis in gliomas regardless of phospho-EGFR expression. The molecular
      characteristics can vary with the increasing age of glioma patients.

PMID- 25618115
TI  - Association analysis of the functional MAOA gene promoter and MAOB gene intron 13
      polymorphisms in tension type headache patients.
AB  - BACKGROUND: Monoamine oxidase (MAO) enzymes play an important role in the
      etiology of many neurological diseases. Tension type headache (TTH) treatments
      contain inhibitors for selective re-uptake of serotonin and monoamine oxidase
      inhibitors. MAO (EC 1.4.3.4) has two isoenzymes known as MAOA and MAOB. A
      promoter polymorphism of a variable number of tandem repeats (VNTR) in the MAOA
      gene seems to affect MAOA transcriptional activity in vitro. Also, G/A
      polymorphism in intron 13 (rs1799836) of the MAOB gene have been previously found
      to be associated with the variability of MAOB enzyme activity. OBJECTIVES: The
      aim of our study was to investigate a possible association of monoamine oxidase
      (MAOA and MAOB) gene polymorphisms in tension type headache. MATERIAL AND
      METHODS: MAO gene polymorphisms were examined in a group of 120 TTH patients and
      in another 168 unrelated healthy volunteers (control group). MAOA promoter and
      MAOB intron 13 polymorphisms were genotyped using PCR-based methods. RESULTS: An
      overall comparison between the genotype of MAOA and MAOB genes and allele
      frequencies of the patients and the control group did not reveal any
      statistically significant difference between the patients and the control group
      (p=0.162). CONCLUSIONS: Factors like estrogen dosage, the limited number of male
      patients and other genes' neurotransmitters involved in the etiology of TTH could
      be responsible for our non-significant results.

PMID- 25618116
TI  - The role of metabolic syndrome and related clinical variables in determining CEA
      levels.
AB  - OBJECTIVES: The aim of the study was to investigate how metabolic syndrome (MetS)
      and related clinical variables correlate with high levels of carcinoembryonic
      antigen (CEA). MATERIAL AND METHODS: Variables related to MetS as well as the
      serum CEA levels of 366 subjects were assayed. Logistic regression analyses were
      used to determine the associations between various clinical variables and high
      CEA levels, which were defined as values greater than the median (i.e., 1.4
      ng/mL). RESULTS: MetS, as an entity, and diabetes were more prevalent in subjects
      with high CEA levels (for MetS: 64.2% in subjects with CEA>=1.4 vs. 51.1% in
      subjects with CEA<1.4 ng/mL, p<0.05; for diabetes: 72.6% vs. 59.1% respectively,
      p<0.05). Waist circumference, triglycerides, fasting plasma glucose (FPG),
      homeostasis-model assessment of insulin resistance index (HOMA-IR), and HbA1c as
      well as systolic and diastolic blood pressures were directly associated with CEA
      levels, after adjusting for age and sex (p<0.05). Subjects with a greater number
      of MetS components tended to have high CEA levels. Multivariate regression
      analysis revealed that the association of waist circumference and FPG with CEA is
      independent of other MetS components, age and sex. CONCLUSIONS: MetS and related
      clinical variables contribute to CEA values. Thus, the reference interval of CEA
      may differ according to the clinical status of the subjects.

PMID- 25618117
TI  - The effects of thyroid dysfunctions on insulin resistance in patients with
      hepatosteatosis.
AB  - BACKGROUND: Hepatosteatosis can develop due to insulin resistance. The effect of
      thyroid function status on insulin sensitivity and resistance is of great
      interest but the data is still conflicting. OBJECTIVES: The aim of this study was
      to evaluate the effects of thyroid dysfunctions on insulin resistance in patients
      with hepatosteatosis. MATERIAL AND METHODS: A total of 407 patients with
      hepatosteatosis were divided into three groups: 102 subjects with hypothyroidism,
      103 with hyperthyroidism and 202 with normal thyroid function (control group). We
      measured serum thyroid stimulating hormone (TSH), free T4 (FT4) and free T3 (FT3)
      concentrations, blood glucose and insulin levels, serum lipid levels, hepatic
      transaminases and the homeostasis model assessment of insulin resistance (HOMA
      IR). RESULTS: Neither hypothyroidism patients nor hyperthyroidism patients showed
      significant differences in HOMA IR, glucose and insulin levels (p>0.05 for each).
      The frequency of insulin resistance was similar in all groups (p>0.05).
      CONCLUSIONS: Based on our findings, hypothyroidism and hyperthyroidism are not
      correlated to insulin resistance in patients with hepatosteatosis. Different
      causes which are associated with insulin resistance should be investigated in
      patients with thyroid dysfunction and hepatosteatosis.

PMID- 25618118
TI  - The effect of sevoflurane vs. TIVA on cerebral oxygen saturation during
      cardiopulmonary bypass--randomized trial.
AB  - BACKGROUND: Neuropsychological and neurological deficits are still major causes
      of mortality and morbidity after cardiac surgery. These complications are thought
      to be caused by embolisms and cerebral hypoxia. Thus, continuous neuromonitoring
      is essential during cardiac surgery due to cerebral oxygen desaturation during
      different periods. Near-infrared spectrophotometry (NIRS), a non-invasive method,
      appears to offer many advantages for monitoring cerebral oxygenation and
      hemodynamics. Desaturation of cerebral oxygen may occur at the beginning of
      cardiopulmonary bypass (CPB) or during the low perfusion and rewarming stages if
      not corrected. OBJECTIVES: This study was designed to assess the effects of
      sevoflurane on cerebral protection during CPB. MATERIAL AND METHODS: Eighty
      patients were divided into two groups. Anesthesia was maintained either with
      fentanyl and midazolam (total intravenous anesthesia, TIVA) or with one minimum
      alveolar concentration of sevoflurane and fentanyl. Cerebral desaturation was
      defined as an absolute decrease in saturation of 20% from baseline cerebral
      saturation. When desaturation occurred, PaCO2, hematocrit and PaO2 levels were
      checked and corrected. If desaturation continued, anesthetic depth was increased
      to reserve saturation with 50-100 mg of propofol. NIRS values and hemodynamics
      were recorded at predetermined time intervals. RESULTS: Cerebral oxygen
      saturation values on the right side were higher in the sevoflurane group than in
      the TIVA group. The values on the left side were higher in the sevoflurane group
      than in the TIVA group, and meaningful differences were seen at the lowest
      temperature and at 36 degrees C. CONCLUSIONS: Oxygen saturation was higher in the
      sevoflurane group than in the TIVA group. Thus, the effect of sevoflurane was
      useful for maintaining cerebral oxygen saturation during CBP.

PMID- 25618119
TI  - Clinical factors in relapses of Wilms' tumor--results for the Polish Pediatric
      Solid Tumors Study Group.
AB  - BACKGROUND: The risk factors responsible for recurrences of Wilms' tumor
      (nephroblastoma) are still under discussion. The aim of the study was to analyze
      the relationship between relapses of Wilms' tumor and the patients' clinical
      history. MATERIAL AND METHODS: Clinical data from children registered in the
      Polish Pediatric Solid Tumors Study Group were analyzed. The clinical stages
      (CS), pathology variants (high risk: HR, intermediate risk: INT, and low risk:
      LOW) and chemotherapy regimens were correlated with the outcomes. RESULTS:
      Recurrences developed in 34 out of 288 (11.8%) patients with Wilms' tumor treated
      in accordance with International Society for Pediatric Oncology 2001 (SIOP 2001)
      protocols. Of these 34 patients, 11 initially had CS I, seven were at CS II, four
      were at CS III, 11 were at CS IV and one had CS V. There were eight patients with
      second recurrences; of these, seven were in the INT risk group and one in the
      high histological risk group. There was no correlation between age (p=0.256) or
      gender (p=0.538) and the risk of tumor recurrence. In the study group, seven out
      of 10 patients with local recurrences are alive; as are 13 out of 22 patients
      with distant recurrences (p=0.703). Those who died due to disease progression
      comprised six out of 26 patients with a first recurrence (four HR, two INT), and
      seven out of eight with a second recurrence (one HR, six INT). CONCLUSIONS: The
      prognosis after relapse in initially metastatic patients did not differ from that
      in patients who had primarily localized disease. The pathology variants probably
      had more significance.

PMID- 25618120
TI  - Serum and urinary MIP-1alpha and IP-10 levels in children with urinary tract
      infections.
AB  - OBJECTIVES: Urinary tract infection (UTI) is a common bacterial disease in
      infants and children, with potentially serious complications, including kidney
      damage. The aim of this study was to test whether serum and urinary levels of
      interleukin-6 (IL-6), macrophage inflammatory protein-1a (MIP-1a) and interferon
      gamma-inducible protein-10 (IP-10) can be used as biomarkers in children with
      urinary tract infections. MATERIAL AND METHODS: The study group consisted of 22
      children with UTI and 20 controls. Blood and urine samples were collected in the
      acute phase and the convalescent phase, on the eighth day after the onset of
      antibiotic therapy. Serum and urine levels of MIP-1a, IP-10 and IL-6 were
      measured. RESULTS: In children with UTI in the acute phase, serum MIP-1a and IL-6
      levels were significantly higher compared to the controls (p<0.05 and p<0.005,
      respectively). A correlation between the serum levels of the chemokines MIP-1a
      and IP-10 in the acute phase was found. CONCLUSIONS: The findings suggest that
      the chemokines MIP-1a or IP-10 respond to infection, but they cannot be used as
      biomarkers for UTI in childhood.

PMID- 25618121
TI  - Dietary supplementation during diabetes therapy and the potential risk of
      interactions.
AB  - BACKGROUND: The classification of dietary supplements as foodstuffs promotes
      widespread access to them and increases the possibility of patients using them
      without being monitored. Unreasonable or excessive consumption of these
      preparations poses risks to type-2 diabetes mellitus (T2DM) patients (among
      others) because it may induce disturbances in glycemic control. The aim of this
      study was to assess the frequency of dietary supplementation among patients using
      anti-diabetic drugs and such patients' nutrient intake in order to evaluate the
      potential risk of interactions. MATERIAL AND METHODS: The study participants were
      150 diabetic patients who were asked about the type of pharmacotherapy and
      dietary supplementation they used. The intake of minerals, vitamins, dietary
      fiber and long-chain polyunsaturated fatty acids (LC-PUFAs) from the patients'
      diets were also assessed, using the 24-h dietary recall method. RESULTS: The
      highest percentage of patients taking individual anti-diabetic drugs used
      supplements containing magnesium and herbs. They also often took antioxidant
      vitamins, B-group vitamins and omega-3 fatty acids. In the majority of patients
      (both those using supplements and those not), the dietary recall showed
      insufficient intake of potassium, calcium and magnesium, as well as of vitamin E,
      folic acid, vitamin D and LC-PUFAs. In addition, their diets provided high median
      amounts of iron, copper, vitamin A and beta-carotene. CONCLUSIONS: The level of
      dietary supplementation and the ill-balanced diets reported by the majority of
      the recruited T2DM patients indicate a high possible risk of interactions with
      the anti-diabetic drugs. Therefore, patients should always consult their
      physicians regarding dietary supplementation, and medically trained staff should
      routinely assess dietary intake to avoid hazardous changes in the activity of
      drugs.

PMID- 25618122
TI  - Gamma-glutamyl transpeptidase as the marker of kidney graft function.
AB  - BACKGROUND: Gamma-glutamyl transpeptidase (GGT) is a glycoprotein of the external
      surface of various cell types. The activity of GGT has been observed in cells and
      tissues with secretory activity, such as the proximal tubular cells in kidneys.
      GGT also plays an important pro-oxidant role, stimulating the generation of
      hydroxyl radicals, and increases membrane lipid peroxidation. OBJECTIVES: In this
      study we examined whether the monitoring of GGT activity in urine may be a
      prognostic factor of kidney allograft function. The study enrolled 107 Caucasian
      renal transplant recipients. MATERIAL AND METHODS: Urine samples were collected
      for GGT and creatinine analysis on the 1st day after transplantation, and then in
      the 3rd and 12th month. RESULTS: Higher urine GGT activity in the 3rd month after
      transplantation was associated with significantly higher risk of graft failure
      (HR=1.063 per each U/g creatinine; 95%Cl:1.004-1.127; p=0.037) in the Cox
      proportional hazards model. Moreover, there were positive correlations between
      urine GGT and the grade of interstitial fibrosis (Rs=0.64, p=0.01) and tubular
      atrophy (Rs=0.54, p=0.056) in specimens collected in the 3rd month after
      transplantation. CONCLUSIONS: Our results suggest that higher urine GGT activity
      in the 3rd month after transplantation may be a prognostic factor of graft
      failure.

PMID- 25618123
TI  - Effect of attending childbirth education classes on psychological distress in
      pregnant women measured by means of the General Health Questionnaire.
AB  - BACKGROUND: Pregnancy brings about many changes in a woman's life in somatic,
      psychological and social spheres. Therefore, many women decide to participate in
      childbirth education classes. The aim of study was to determine the differences
      in emotional distress between women who participated in childbirth education
      classes and these who did not. MATERIAL AND METHODS: Seventy first-time mothers
      after labor were examined. Based on a survey carried out, the women were divided
      into two equal groups. Group I consisted of women who had participated in
      childbirth education classes and Group II of women who had not. The data was
      gathered by means of the General Health Questionnaire (GHQ-12) adapted to Polish
      conditions. RESULTS: There were no differences either in age or in BMI rates
      among the examined women. The level of education and knowledge about labor was
      significantly higher among the participants of childbirth classes. The results of
      the GHQ-12 revealed that women from Group I had a better mental status than women
      from Group II. Significant differences were observed in terms of sleep
      deprivation, overcoming difficulties and in the ability to enjoy daily
      activities. CONCLUSIONS: Participation in childbirth classes has a significant
      influence on psychological well-being in pregnant women as measured by the GHQ
      12.

PMID- 25618124
TI  - Soluble urokinase-type plasminogen activator receptor and ferritin concentration
      in patients with advanced alimentary tract carcinoma. Relationship to
      localization, surgical treatment and the stage of the disease--preliminary
      report.
AB  - BACKGROUND: The urokinase plasminogen activation system is associated with
      metastatic potential of cancer in several tumors. Its specific membrane receptor
      (uPAR) is released from cancer cells and can be detected as the soluble fraction
      of the plasminogen activator receptor (suPAR). Ferritin (FRT) is a poor
      prognostic factor in various neoplasms. OBJECTIVES: We analyzed the serum
      concentrations of suPAR and FRT in patients with gastrointestinal cancer. Tumor
      localization, stage of the disease, possibility of surgery and histopathological
      diagnosis were considered. MATERIAL AND METHODS: The analysis involved 48
      patients (8 females/40 males) treated in the Department of Gastrointestinal and
      General Surgery, Wroclaw Medical University. Thirty two patients had esophageal,
      7-gastric, 9-colorectal cancer. Fifteen patients underwent resection surgery, 33
      palliative therapy. The control comprised 10 healthy donors. The serum
      concentration of suPAR was determined by enzyme-linked immunosorbent assay
      (ELISA), expressed in pg/mL. Concentration of the serum FRT was detected using
      immunonephelometry method, expressed in ug/L. RESULTS: Serum concentration of
      suPAR ranged from 1789-7320, x=3676.2, SD=1042 and was significantly higher
      (p=0.0002) than in the control group. In patients who underwent palliative
      therapy, the concentration of suPAR was significantly higher (p=0.05) than in
      those after resection, also in patients with esophageal cancer compared to those
      with colorectal one (p=0.02). Serum concentration of FRT in patients with
      gastrointestinal cancer was significantly higher than in control group. Serum FRT
      concentration was higher in patients with esophageal cancer compared to patients
      with gastric cancer (p=0.05), in persons with IV compared to patients with I-III
      stage of the disease, patients who underwent palliative compared to surgical
      therapy. CONCLUSIONS: In patients with gastrointestinal cancer the level of suPAR
      is high, with highest values in advances disease with remote metastases. The FRT
      concentration is sensitive indicator of the disease process: its level is highest
      in pts with IV stage who underwent palliative therapy.

PMID- 25618125
TI  - Comparison of high-frequency and MIST ultrasound therapy for the healing of
      venous leg ulcers.
AB  - BACKGROUND: Venous leg ulcers (VLUs) are a health problem in clinical care.
      Several options can be employed as adjuvant to standard treatment. OBJECTIVES: We
      have aimed to analyze the effect of standard ulcer care alone with high-frequency
      ultrasound (HFU) and MIST ultrasound therapy on VLUs. MATERIAL AND METHODS:
      Ninety patients with VLUs were assigned into the standard treatment, HFU and MIST
      ultrasound groups. All groups received the standard wound care. In the ultrasound
      groups, HFU and MIST ultrasound therapy was administered to wounds 3 times per
      week until the wound healed. Time of complete wound healing was recorded. Wound
      size, pain, and edema were assessed at baseline and after 2 and 4 months. Also,
      patients were instructed to contact our clinic monthly, and recurrence of VLUs
      was recorded for 6 months after complete wound healing. The data was analyzed
      using a Student's t-test, ANOVA, c2, or Fisher's exact test. P<0.05 was
      considered significant. RESULTS: Mean time duration of complete wound healing in
      the first, second and third groups was 8.13 (SD 1.40), 6.10 (SD 1.47) and 5.70
      (SD 1.57) months, respectively (p<0.0001). Size of ulcer, mean degree of pain and
      edema in ultrasound therapy was decreased after the 4-month visit in comparison
      to the standard-treatment group (p=0.01, p<0.0001 and p<0.0001, respectively).
      Also, our results don't show any significant differences between groups in the
      recurrence of VLUs during a 6-month follow up after complete wound healing
      (p=0.37). CONCLUSIONS: Our results in the present study show the significant
      effectiveness of ultrasound therapy in wound healing. Differences between the two
      ultrasound therapy groups were not statistically significant.

PMID- 25618126
TI  - The use of light-cured resin as an alternative method of occlusal splints
      manufacturing--in vitro study.
AB  - BACKGROUND: Temporomandibular disorders are very common nowadays. One of the
      methods to treat these problems is occlusal splint therapy. Modern materials
      should be introduced to this treatment. OBJECTIVES: The aim of this paper was to
      evaluate the properties of light-activated urethane dimethacrylate and the
      quality of the bonds it creates with thermoforming foils. MATERIAL AND METHODS:
      Thermoforming foils were covered with light-cured resin. A bond was formed
      between the materials using an adhesive. A coating lacquer was used on the resin
      as a final preparatory step. Three laboratory tests were run: dye penetrant
      inspection, a Vickers microhardness test and a linear polymerization shrinkage
      test. The materials were layered and then cured with a polymerizing lamp emitting
      light of a wavelength of 400 Nm, according to the manufacturer's instructions.
      All the occlusal splints were fitted to upper dental arch. The devices had been
      made in an articulator on specially prepared gypsum models. The results were
      analyzed statistically using a one-sided binomial test, Spearman's rank-order
      correlation coefficient and the Friedman ANOVA (p=0.05). RESULTS: In the dye
      penetrant inspection, only one sample out of sixty showed the effects of color
      penetration to the adhesive connection. The dye only penetrated the layer of
      lacquer coating the resin. The average value of the Vickers microhardness test
      with a load of F=50 g applied to the material surface for 30 s was HV0.05=7.43
      N/mm2. The average linear shrinkage of the resin observed after polymerization
      was 1.175%. CONCLUSIONS: Light-cured resin and an adhesive connection between the
      resin and thermoforming foil do not show susceptibility even to strong dye. The
      maximum polymerization shrinkage occurs immediately after curing. The light-cured
      resin that was tested seems to be a good alternative method for occlusal splints
      manufacturing.

PMID- 25618127
TI  - The lifetime prevalence of anxiety disorders among patients with irritable bowel
      syndrome.
AB  - BACKGROUND: The prevalence of irritable bowel syndrome (IBS), the most common
      functional gastrointestinal disorder, ranges from 10% to 20% in the general
      population. It is estimated that from 40% to 90% of persons with a diagnosis of
      IBS suffer from mental disorders, mainly anxiety and depressive disorders.
      OBJECTIVES: The aim of the study was to assess the lifetime prevalence of anxiety
      disorders in IBS patients and to compare it with the prevalence of these
      disorders in a control group of patients with gastroesophageal reflux disease
      (GERD). MATERIAL AND METHODS: The study included 106 patients with IBS and 53
      patients with GERD. IBS was diagnosed according to the Rome II criteria after a
      basic evaluation to exclude an organic disease. Anxiety disorders were diagnosed
      using the Composite International Diagnostic Interview (CIDI) in accordance with
      ICD-10 diagnostic criteria. RESULTS: Anxiety disorders during the patient's
      lifetime were diagnosed in 50 IBS patients (47%). Specific phobias occurred in
      23.5% of them, social phobias in 10.4%, generalized anxiety disorder in 10.4%,
      panic disorder in 3.8% and agoraphobia in 8.5%. In the control group with GERD,
      anxiety disorders during the subject's lifetime were diagnosed in 30% of the
      group. The difference in the prevalence of anxiety disorders between patients
      with IBS and GERD was statistically significant (p<0.05). CONCLUSIONS: The
      lifetime prevalence of anxiety disorders in IBS patients was higher than in the
      control group with GERD (47% vs. 30%). The prevalence rate of anxiety disorders
      in the control group with GERD was similar to the prevalence rate in the general
      population.

PMID- 25618128
TI  - The impact of combinations of non-steroidal anti-inflammatory drugs and anti
      hypertensive agents on blood pressure.
AB  - Nowadays NSAIDs are the most frequently used groups of drugs, especially because
      of their availability. Their consumption is high among older people, who are much
      more sensitive to the side effects, and who are often also taking other drugs
      which can interact with them. Moreover, the majority of the older population is
      suffering from hypertension. This could well explain the commonly encountered
      experience of drug interaction between NSAIDs and antihypertensive drugs, which
      is very common in clinical practice. The severity of this drug interaction is
      classified as class C, with a recommendation to monitor therapy. However, even a
      minor long-term increase in blood pressure can significantly increase the risk of
      cardiovascular mortality, while mortality rates can possibly be reduced by
      sufficiently effective treatment of hypertension. Therefore, in clinical
      practice, this type of interaction should not be overlooked as a major cause of
      failure of hypertension treatment in older patients, as well in many cases in
      general. The present article focusses on the mechanism and the degree of
      influence on the blood pressure of particular types of antihypertensive agents
      used in combination with NSAID. Not all groups of antihypertensive drugs are
      affected to the same degree; some are more affected, and others, such as calcium
      channel blockers, are not affected at all. Similarly, not every NSAID increases
      blood pressure. Many studies, some of which are analyzed in this article, present
      evidence of the degree of the influence NSAIDs have on blood pressure. 

PMID- 25618129
TI  - The use of central venous lines in the treatment of chronically ill children.
AB  - Treatment of chronic diseases in children is a special medical problem.
      Maintaining constant access to the central vascular system is necessary for long
      term hemato-oncological and nephrological therapies as well as parenteral
      nutrition. Providing such access enables chemotherapic treatment, complete
      parenteral nutrition, long-term antibiotic therapy, hemodialysis, treatment of
      intensive care unit patients, monitoring blood pressure in the pulmonary artery
      and stimulation of heart rate in emergency situations as well as treatment of
      patients suffering from complications, especially when chances of access into
      peripheral veins are exhausted. Continuous access to the central vascular system
      is desirable in the treatment of chronically ill children. Insertion of a central
      venous catheter line eliminates the unnecessary pain and stress to a child
      patient accompanying injection into peripheral vessels. In order to gain long
      term and secure access to the central venous system, respecting the guidelines of
      the Center for Disease Control and Prevention contained in the updated
      'Guidelines for the Prevention of Intravascular Catheter-Related Infections' is
      necessary. 

PMID- 25618130
TI  - The use of stem cells in plastic and reconstructive surgery.
AB  - As part of their clinical practice, plastic surgeons perform procedures in the
      fields of skin and adipose tissue grafting, the reconstruction of compound tissue
      loss and congenital malformations, the treatment of acute and chronic wounds and
      burns, as well as cosmetic surgery. On account of the great expectations
      associated with their use in therapy, stem cells (SCs) are increasingly
      frequently employed in in vitro experiments, animal models and clinical trials.
      The most commonly utilized SCs for these purposes are adult stem cells (AS),
      which are present in small amounts in every tissue; among these are two types of
      cells: bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived stem
      cells (ADSCs). The aim of this review is to present current findings in
      experimental research on the use of stem cells in the field of plastic and
      reconstructive surgery. Many studies have described the progress of trials using
      ADSCs and BM-MSCs mainly in the treatment of compound tissue loss and chronic
      wounds. The use of their paracrine, proangiogenic and osteogenic functions is
      emphasized. However, because of the very high harvesting and culturing expenses
      and the limited availability of data on their safety for human use, SCs are not a
      first-choice therapy. Further developments in SC research and gradually
      decreasing costs mean that along with commercial-scale SC culturing, the use of
      SCs will become a viable alternative to traditional surgical procedures. 

PMID- 25618131
TI  - Head and neck cancer patients' quality of life.
AB  - Patients suffering from head and neck cancers often require a multidisciplinary
      approach before and after surgery. Restoration of facial esthetics, speech,
      mastication and others often requires a long-lasting, divided rehabilitation.
      Quality of life (QOL) is measurable in a patient's life before and after surgery
      and complete treatment. The state of QOL has different parameters depending on
      the patient's clinical diagnosis, type of treatment and surgeries performed. In
      this paper, the authors are focusing on the quality of life of patients suffering
      from head and neck cancers and a proper multidisciplinary approach to achieving
      proper functions will be described. Also, the patient's self-esteem improvement
      and psychological evaluation is necessary. 

PMID- 25618132
TI  - Identification of Ancylostoma ceylanicum in children from a tribal community in
      Tamil Nadu, India using a semi-nested PCR-RFLP tool.
AB  - BACKGROUND: It is generally assumed that hookworm infections in humans are caused
      by Necator americanus and Ancylostoma duodenale. However, previous studies have
      also reported the presence of the animal hookworm A. ceylanicum in human stools.
      METHODS: We determined hookworm infections in children in a tribal community in
      Tamil Nadu, India, using a semi-nested PCR-RFLP approach. RESULTS: The results
      indicate that human species account for a majority of the hookworm infections (N.
      americanus 39/41 [95%]; A. duodenale 6/41 [15%]), whereas the animal hookworm A.
      ceylanicum only accounts for a minority of the infections (5%; 2/41).
      CONCLUSIONS: The results emphasize the need to consider zoonotic ancylostomiasis
      while developing strategies to control hookworm infections.

PMID- 25618133
TI  - Noncompaction cardiomyopathy: a substrate for a thromboembolic event.
AB  - BACKGROUND: Noncompaction cardiomyopathy (NCC) is a rare genetic cardiomyopathy
      characterized by a thin, compacted epicardial layer and an extensive noncompacted
      endocardial layer. The clinical manifestations of this disease include
      ventricular arrhythmia, heart failure, and systemic thromboembolism. CASE
      PRESENTATION: A 43-year-old male was anticoagulated by pulmonary thromboembolism
      for 1 year when he developed progressive dyspnea. Cardiovascular magnetic
      resonance imaging showed severe biventricular trabeculation with an ejection
      fraction of 15%, ratio of maximum noncompacted/compacted diastolic myocardial
      thickness of 3.2 and the presence of exuberant biventricular apical thrombus.
      CONCLUSION: Still under discussion is the issue of which patients and when they
      should be anticoagulated. It is generally recommended to those presenting
      ventricular systolic dysfunction, antecedent of systemic embolism, presence of
      cardiac thrombus and atrial fibrillation. In clinical practice the patients with
      NCC and ventricular dysfunction have been given oral anticoagulation, although
      there are no clinical trials showing the real safety and benefit of this
      treatment.

PMID- 25618134
TI  - Dementia in multiple sclerosis: why is it rarely discussed?
AB  - Cognitive deficits in multiple sclerosis (MS) have been well studied in decades
      of MS research. Severe deficits are acknowledged, but the frequency is minimized
      in the literature, and there is a striking lack of discussion of the presence of
      a dementia state in MS. Possible reasons for this omission are discussed, along
      with an argument to define the dementia state and to provide terminology that
      will be palatable to patients. 

PMID- 25618135
TI  - The role of processing speed in post-stroke cognitive dysfunction.
AB  - The association between speed of information processing and cognition has been
      extensively validated in normal aging and other neurocognitive disorders. Our aim
      was to determine whether such a relationship exists in stroke. Thirty patients
      and 30 age- and education-matched healthy individuals were administered a
      comprehensive battery of neuropsychological tests divided into the following six
      cognitive domains: processing speed (PS), verbal memory, visual memory,
      visuoperceptual function, language, and cognitive flexibility. The results
      demonstrate that stroke patients were characterized by cognitive deficits in
      almost all of these domains, but have the most pronounced deficits in PS. After
      adjusting for symbol digit modalities test score, all significant group
      differences in cognitive functioning disappeared. However, group differences
      remained significant after controlling for the influence of other cognitive
      factors. These findings suggest that decreased PS appears to underlie post-stroke
      cognitive dysfunction and may serve as a potential target for intervention. 

PMID- 25618136
TI  - Development of a wavelength-separated type scintillator with optical fiber (SOF)
      dosimeter to compensate for the Cerenkov radiation effect.
AB  - The scintillator with optical fiber (SOF) dosimeter consists of a miniature
      scintillator mounted on the tip of an optical fiber. The scintillator of the
      current SOF dosimeter is a 1-mm diameter hemisphere. For a scintillation
      dosimeter coupled with an optical fiber, measurement accuracy is influenced by
      signals due to Cerenkov radiation in the optical fiber. We have implemented a
      spectral filtering technique for compensating for the Cerenkov radiation effect
      specifically for our plastic scintillator-based dosimeter, using a wavelength
      separated counting method. A dichroic mirror was used for separating input light
      signals. Individual signal counting was performed for high- and low-wavelength
      light signals. To confirm the accuracy, measurements with various amounts of
      Cerenkov radiation were performed by changing the incident direction while
      keeping the Ir-192 source-to-dosimeter distance constant, resulting in a
      fluctuation of <5%. Optical fiber bending was also addressed; no bending effect
      was observed for our wavelength-separated SOF dosimeter. 

PMID- 25618138
TI  - Correction.

PMID- 25618137
TI  - A comparison of the dose distributions between the brachytherapy 125I source
      models, STM1251 and Oncoseed 6711, in a geometry lacking radiation equilibrium
      scatter conditions.
AB  - The purpose of this study was to estimate the uncertainty in the dose
      distribution for the (125)I source STM1251, as measured with a
      radiophotoluminescent glass rod dosimeter and calculated using the Monte Carlo
      code EGS5 in geometry that included the source structure reported by Kirov et al.
      This was performed at a range of positions in and on a water phantom 18 cm in
      diameter and 16 cm in length. Some dosimetry positions were so close to the
      surface that the backscatter margin was insufficient for photons. Consequently,
      the combined standard uncertainty (CSU) at the coverage factor k of 1 was 11.0
      11.2% for the measurement and 1.8-3.6% for the calculation. The calculation
      successfully reproduced the measured dose distribution within 13%, with CSU at k
      <= 1.6 (P > 0.3). Dose distributions were then compared with those for the (125)I
      source Oncoseed 6711. Our results supported the American Association of
      Physicists in Medicine Task Group No. 43 Updated Protocol (TG43U1) formalism, in
      which STM1251 dose distributions were more penetrating than those of Oncoseed
      6711. This trend was also observed in the region near the phantom surface lacking
      the equilibrium radiation scatter conditions. In this region, the difference
      between the TG43U1 formalism and the measurement and calculation performed in the
      present study was not significant (P > 0.3) for either of the source models.
      Selection of the source model based on the treatment plans according to the
      TG43U1 formalism will be practical. 

PMID- 25618139
TI  - Improving screening recall services for women with false-positive mammograms: a
      comparison of qualitative evidence with UK guidelines.
AB  - OBJECTIVES: To gain an understanding of the views of women with false-positive
      screening mammograms of screening recall services, their ideas for service
      improvements and how these compare with current UK guidelines. METHODS: Inductive
      qualitative content analysis of semistructured interviews of 21 women who had
      false-positive screening mammograms. These were then compared with UK National
      Health Service (NHS) guidelines. RESULTS: Participants' concerns about
      mammography screening recall services focused on issues of communication and
      choice. Many of the issues raised indicated that the 1998 NHS Breast Screening
      Programme guidelines on improving the quality of written information sent to
      women who are recalled, had not been fully implemented. This included being told
      a clear reason for recall, who may attend with them, the length of appointment,
      who they will see and what tests will be carried out. Additionally women voiced a
      need for: reassurance that a swift appointment did not imply they had cancer;
      choice about invasive assessment or watchful waiting; the offer of a follow-up
      mammogram for those uncertain about the validity of their all-clear and an
      extension of the role of the clinical nurse specialist, outlined in the 2012 NHS
      Breast Screening Programme (NHSBSP) guidelines, to include availability at the
      clinic after the all-clear for women with false-positive mammograms. CONCLUSIONS:
      It is time the NHSBSP 1998 recall information guidelines were fully implemented.
      Additionally, the further suggestions from this research, including extending the
      role of the clinical nurses from the 2012 NHSBSP guidelines, should be
      considered. These actions have the potential to reduce the anxiety of being
      recalled.

PMID- 25618140
TI  - Spatial dynamics of evolving dosage compensation in a young sex chromosome
      system.
AB  - The loss of Y-linked genes during sex chromosome evolution creates a potentially
      deleterious low gene dosage in males. Recent studies have reported different
      strategies of dosage compensation. Unfortunately, most of these studies
      investigated taxa with comparatively old sex chromosome systems, which may limit
      insights into the evolution of dosage compensation and thus into the causes of
      different compensation strategies. Using deep RNA sequencing, we investigate
      differential expression patterns along the young XY chromosomes of threespine
      sticklebacks. Our strata-specific analyses provide new insights into the spatial
      patterns during the early stages of the evolution of dosage compensation. In
      particular, our results indicate systematic upregulation of male gene expression
      in stratum II, which in turn causes female hypertranscription in the same
      stratum. These findings are consistent with theoretical predictions that
      selection during early stages of sex chromosome evolution is stronger for a
      compensating upregulation in males than for the countercompensation of female
      hyperexpression. In contrast, no elevated gene expression is detectable in
      stratum I. We argue that strata-specific differences in compensating male gene
      expression may evolve in response to differences in the prevailing mechanism of Y
      chromosome degeneration.

PMID- 25618142
TI  - A Coxiella-like endosymbiont is a potential vitamin source for the Lone Star
      tick.
AB  - Amblyomma americanum (Lone star tick) is an important disease vector in the
      United States. It transmits several human pathogens, including the agents of
      human monocytic ehrlichiosis, tularemia, and southern tick-associated rash
      illness. Blood-feeding insects (Class Insecta) depend on bacterial endosymbionts
      to provide vitamins and cofactors that are scarce in blood. It is unclear how
      this deficiency is compensated in ticks (Class Arachnida) that feed exclusively
      on mammalian blood. A bacterium related to Coxiella burnetii, the agent of human
      Q fever, has been observed previously within cells of A. americanum. Eliminating
      this bacterium (CLEAA, Coxiella-like endosymbiont of A. americanum) with
      antibiotics reduced tick fecundity, indicating that it is an essential
      endosymbiont. In an effort to determine its role within this symbiosis, we
      sequenced the CLEAA genome. While highly reduced (656,901 bp) compared with C.
      burnetii (1,995,281 bp), the CLEAA genome encodes most major vitamin and cofactor
      biosynthesis pathways, implicating CLEAA as a vitamin provisioning endosymbiont.
      In contrast, CLEAA lacks any recognizable virulence genes, indicating that it is
      not a pathogen despite its presence in tick salivary glands. As both C. burnetii
      and numerous "Coxiella-like bacteria" have been reported from several species of
      ticks, we determined the evolutionary relationship between the two bacteria.
      Phylogeny estimation revealed that CLEAA is a close relative of C. burnetii, but
      was not derived from it. Our results are important for strategies geared toward
      controlling A. americanum and the pathogens it vectors, and also contribute novel
      information regarding the metabolic interdependencies of ticks and their nutrient
      provisioning endosymbionts. 

PMID- 25618141
TI  - Highly constrained intergenic Drosophila ultraconserved elements are candidate
      ncRNAs.
AB  - Eukaryotes contain short (~80-200 bp) regions that have few or no substitutions
      among species that represent hundreds of millions of years of evolutionary
      divergence. These ultraconserved elements (UCEs) are candidates for containing
      essential functions, but their biological roles remain largely unknown. Here, we
      report the discovery and characterization of UCEs from 12 sequenced Drosophila
      species. We identified 98 elements >=80 bp long with very high conservation
      across the Drosophila phylogeny. Population genetic analyses reveal that these
      UCEs are not present in mutational cold spots. Instead we infer that they
      experience a level of selective constraint almost 10-fold higher compared with
      missense mutations in protein-coding sequences, which is substantially higher
      than that observed previously for human UCEs. About one-half of these Drosophila
      UCEs overlap the transcribed portion of genes, with many of those that are within
      coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For
      the remaining UCEs that are in nongenic regions, we find that many are
      potentially capable of forming RNA secondary structures. Among ten chosen for
      further analysis, we discovered that the majority are transcribed in multiple
      tissues of Drosophila melanogaster. We conclude that Drosophila species are rich
      with UCEs and that many of them may correspond to novel noncoding RNAs. 

PMID- 25618143
TI  - Genetic structure of Miscanthus sinensis and Miscanthus sacchariflorus in Japan
      indicates a gradient of bidirectional but asymmetric introgression.
AB  - Unilateral introgression from diploids to tetraploids has been hypothesized to be
      an important evolutionary mechanism in plants. However, few examples have been
      definitively identified, perhaps because data of sufficient depth and breadth
      were difficult to obtain before the advent of affordable high-density genotyping.
      Throughout Japan, tetraploid Miscanthus sacchariflorus and diploid Miscanthus
      sinensis are common, and occasionally hybridize. In this study, 667 M. sinensis
      and 78 M. sacchariflorus genotypes from Japan were characterized using 20 704
      SNPs and ten plastid microsatellites. Similarity of SNP genotypes between diploid
      and tetraploid M. sacchariflorus indicated that the tetraploids originated
      through autopolyploidy. Structure analysis indicated a gradient of introgression
      from diploid M. sinensis into tetraploid M. sacchariflorus throughout Japan; most
      tetraploids had some M. sinensis DNA. Among phenotypically M. sacchariflorus
      tetraploids, M. sinensis ancestry averaged 7% and ranged from 1-39%, with
      introgression greatest in southern Japan. Unexpectedly, rare (~1%) diploid M.
      sinensis individuals from northern Japan were found with 6-27% M. sacchariflorus
      ancestry. Population structure of M. sinensis in Japan included three groups, and
      was driven primarily by distance, and secondarily by geographic barriers such as
      mountains and straits. Miscanthus speciation is a complex and dynamic process. In
      contrast to limited introgression between diploid M. sacchariflorus and M.
      sinensis in northern China, selection for adaptation to a moderate maritime
      climate probably favoured cross-ploidy introgressants in southern Japan. These
      results will help guide the selection of Miscanthus accessions for the breeding
      of biomass cultivars. 

PMID- 25618144
TI  - Leaf expansion of soybean subjected to high and low atmospheric vapour pressure
      deficits.
AB  - Vapour pressure deficit (VPD) is considered an important environmental factor
      that might affect leaf expansion and transpiration rate (TR) in plants. Two slow
      wilting soybean (Glycine max (L.) Merr.) genotypes PI 416937 and PI 471938 along
      with commercial cultivar Hutcheson were subjected to low (1.2-1.6 kPa) and high
      VPD (2.8-3 kPa) environments to study their leaf expansion and TR over five days.
      Among the three genotypes, PI 416937 had the lowest increase in its TR (34%) at
      high VPD compared with low VPD and the greatest decrease in leaf area (31%). In
      contrast, Hutcheson had the highest increase in TR (87%) under high VPD and the
      lowest decrease in leaf expansion rate (18%). Expansin and extensin genes were
      isolated in PI 416937 to determine if changes in leaf expansion were associated
      with changes at the molecular level. The four studied genes were all suppressed
      after five days in the high VPD environment. 

PMID- 25618145
TI  - Metabolic profiling of Lolium perenne shows functional integration of metabolic
      responses to diverse subtoxic conditions of chemical stress.
AB  - Plant communities are confronted with a great variety of environmental chemical
      stresses. Characterization of chemical stress in higher plants has often been
      focused on single or closely related stressors under acute exposure, or
      restricted to a selective number of molecular targets. In order to understand
      plant functioning under chemical stress conditions close to environmental
      pollution conditions, the C3 grass Lolium perenne was subjected to a panel of
      different chemical stressors (pesticide, pesticide degradation compound,
      polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level
      or root-level subtoxic exposure. Physiological and metabolic profiling analysis
      on roots and shoots revealed that all of these subtoxic chemical stresses
      resulted in discrete physiological perturbations and complex metabolic shifts.
      These metabolic shifts involved stressor-specific effects, indicating multilevel
      mechanisms of action, such as the effects of glyphosate and its degradation
      product aminomethylphosphonic acid on quinate levels. They also involved major
      generic effects that linked all of the subtoxic chemical stresses with major
      modifications of nitrogen metabolism, especially affecting asparagine, and of
      photorespiration, especially affecting alanine and glycerate. Stress-related
      physiological effects and metabolic adjustments were shown to be integrated
      through a complex network of metabolic correlations converging on Asn, Leu, Ser,
      and glucose-6-phosphate, which could potentially be modulated by differential
      dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and
      glucose). Underlying metabolic, regulatory, and signalling mechanisms linking
      these subtoxic chemical stresses with a generic impact on nitrogen metabolism and
      photorespiration are discussed in relation to carbohydrate and low-energy
      sensing. 

PMID- 25618146
TI  - Erratum: Expression changes of ionic channels in early phase of cultured rat
      atrial myocytes induced by rapid pacing.

PMID- 25618147
TI  - Global trends in health research and development expenditures--the challenge of
      making reliable estimates for international comparison.
AB  - Better estimates of changes in the level and structure of national, regional, and
      global expenditures on health research and development (R&D) are needed as an
      important source of information for advancing countries' health research
      policies. However, such estimates are difficult to compile and comparison between
      countries needs careful calibration. We outline the steps that need to be taken
      to make reliable estimates of trends in countries' expenditures on health R&D,
      describe that an ideal approach would involve the use of international sets of
      deflators and exchange rates that are specific to health R&D activities, and
      explain which methods should be used given the current absence of such health R&D
      specific deflators and exchange rates. Finally, we describe what should be the
      way forward in improving our ability to make reliable estimates of trends in
      countries' health R&D expenditures. 

PMID- 25618149
TI  - Patient-centered physician selection: a necessary first step for accountable
      care.

PMID- 25618150
TI  - Reducing risk and improving efficacy of clinical trials: the adaptive design.

PMID- 25618148
TI  - A SelB/EF-Tu/aIF2gamma-like protein from Methanosarcina mazei in the GTP-bound
      form binds cysteinyl-tRNA(Cys.).
AB  - The putative translation elongation factor Mbar_A0971 from the methanogenic
      archaeon Methanosarcina barkeri was proposed to be the pyrrolysine-specific
      paralogue of EF-Tu ("EF-Pyl"). In the present study, the crystal structures of
      its homologue from Methanosarcina mazei (MM1309) were determined in the GMPPNP
      bound, GDP-bound, and apo forms, by the single-wavelength anomalous dispersion
      phasing method. The three MM1309 structures are quite similar (r.m.s.d. < 0.1 A).
      The three domains, corresponding to domains 1, 2, and 3 of EF-Tu/SelB/aIF2gamma,
      are packed against one another to form a closed architecture. The MM1309
      structures resemble those of bacterial/archaeal SelB, bacterial EF-Tu in the GTP
      bound form, and archaeal initiation factor aIF2gamma, in this order. The GMPPNP
      and GDP molecules are visible in their co-crystal structures. Isothermal
      titration calorimetry measurements of MM1309.GTP.Mg(2+), MM1309.GDP.Mg(2+), and
      MM1309.GMPPNP.Mg(2+) provided dissociation constants of 0.43, 26.2, and 222.2
      MUM, respectively. Therefore, the affinities of MM1309 for GTP and GDP are
      similar to those of SelB rather than those of EF-Tu. Furthermore, the switch I
      and II regions of MM1309 are involved in domain-domain interactions, rather than
      nucleotide binding. The putative binding pocket for the aminoacyl moiety on
      MM1309 is too small to accommodate the pyrrolysyl moiety, based on a comparison
      of the present MM1309 structures with that of the EF-Tu.GMPPNP.aminoacyl-tRNA
      ternary complex. A hydrolysis protection assay revealed that MM1309 binds
      cysteinyl (Cys)-tRNA(Cys) and protects the aminoacyl bond from non-enzymatic
      hydrolysis. Therefore, we propose that MM1309 functions as either a guardian
      protein that protects the Cys moiety from oxidation or an alternative translation
      factor for Cys-tRNA(Cys). 

PMID- 25618151
TI  - Studies see value of prostate cancer diagnostic test, but will CMS pay for it?

PMID- 25618152
TI  - Digital technologies gain popularity for smoking cessation: evidence strongly
      supports some.

PMID- 25618154
TI  - In New Jersey, focus in fight against cancer changes, and care comes closer to
      home.

PMID- 25618153
TI  - Robotic-assisted surgery: a question of value.

PMID- 25618155
TI  - FDA moves to regulate thousands of diagnostic tests.

PMID- 25618156
TI  - A new method to fight cancer: the body's own immune system.

PMID- 25618157
TI  - ASCO's initiative to define value in cancer care.

PMID- 25618158
TI  - How do you establish value in cancer care?

PMID- 25618159
TI  - MMRF efforts attack the disease from every angle; a transformation is on the
      horizon.

PMID- 25618160
TI  - AJMC panel: advances in multiple myeloma therapy extend survival for patients,
      raising cost concerns.

PMID- 25618161
TI  - AJMC panel asks: does it pay to use pathways?

PMID- 25618162
TI  - Progression of lower and higher-order aberrations: a longitudinal study.
AB  - BACKGROUND: The aim of the present study was to investigate the effect of near
      work on lower and higher-order aberrations, and its progression over a 9-month
      period during the school year. METHODS: Data from 24 young-adult myopic eyes, and
      24 non-myopic eyes were used in this investigation. The lower-order aberrations,
      coma, spherical aberration (SA), and total root mean square (RMS) of higher order
      aberrations (total HOA) were measured using an open-field iTrace aberrometer, at
      both the initial baseline evaluation, and then at the follow-up visits over a 9
      month period. Pupil size of 4 mm was used for the aberration measurements.
      RESULTS: The group mean (SD) of the subjects (mean age: 23.6 +/- 3.4 years) at
      the initial and follow-up visit was 0.47D (0.47D) and 0.31D (0.41D), in the non
      myopes and -3.58D (2.08D) and -3.86D (2.14D) in the myopes, respectively.
      Significant increases in myopic refraction were observed. The group mean (SD)
      total HOA at the initial and final visit was 0.12 (0.08) and 0.11 (0.06) microns,
      in the non-myopes, and 0.15 (0.08) and 0.15 (0.08) microns, in the myopes,
      respectively. The group mean RMS of the coma at the initial and final visit was
      0.06 (0.04) and 0.07 (0.05), in the non-myopes, and 0.08 (0.06) and 0.09 (0.06)
      microns, in the myopes, respectively. The group mean SA of the subjects at the
      initial and last visit was 0.04 (0.04) and 0.03 (0.03), in the non-myopes, and
      0.04 (0.04) and 0.04 (0.04) microns, in the myopes, respectively. CONCLUSIONS:
      There was a significant difference in myopic refraction, over the 9-month
      assessment period. However, no significant difference in total HOA, SA, and coma
      between the initial and follow-up visits in both the myopes and the non-myopes
      was observed.

PMID- 25618163
TI  - Familial impact and coping with child heart disease: a systematic review.
AB  - Families of children with congenital heart disease (CHD) cope differently
      depending on individual and familial factors beyond the severity of the child's
      condition. Recent research has shifted from an emphasis on the psychopathology of
      family functioning to a focus on the resilience of families in coping with the
      challenges presented by a young child's condition. The increasing number of
      studies on the relationship between psychological adaptation, parental coping and
      parenting practices and quality of life in families of children with CHD
      necessitates an in-depth re-exploration. The present study reviews published
      literature in this area over the past 25 years to generate evidence to inform
      clinical practice, particularly to better target parent and family interventions
      designed to enhance family coping. Twenty-five studies were selected for
      inclusion, using the PRISMA guidelines. Thematic analysis identified a number of
      themes including psychological distress and well-being, gender differences in
      parental coping, and variable parenting practices and a number of subthemes.
      There is general agreement in the literature that families who have fewer
      psychosocial resources and lower levels of support may be at risk of higher
      psychological distress and lower well-being over time, for both parent and the
      child. Moreover, familial factors such as cohesiveness and adaptive parental
      coping strategies are necessary for successful parental adaptation to CHD in
      their child. The experiences, needs and ways of coping in families of children
      with CHD are diverse and multi-faceted. A holistic approach to early psychosocial
      intervention should target improved adaptive coping and enhanced productive
      parenting practices in this population. This should lay a strong foundation for
      these families to successfully cope with future uncertainties and challenges at
      various phases in the trajectory of the child's condition.

PMID- 25618164
TI  - How Slow Can We Go? 4 Frames Per Second (fps) Versus 7.5 fps Fluoroscopy for
      Atrial Septal Defects (ASDs) Device Closure.
AB  - Radiation exposure remains a significant concern for ASD device closure. In an
      effort to reduce radiation exposure, the default fluoroscopy frame rate in our
      Siemens biplane pediatric catheterization laboratory was reduced to 4 fps in
      November 2013 from an earlier 7.5 fps fluoro rate. This study aims to evaluate
      the components contributing to total radiation exposure and compare the
      procedural success and radiation exposure during ASD device closure using 4
      versus 7.5 fps fluoroscopy rates. Twenty ASD device closures performed using 4
      fps fluoro rate were weight-matched to 20 ASD closure procedures using 7.5 fps
      fluoro rate. Baseline characteristics, procedure times and case times were
      similar in the two groups. Device closure was successful in all but one case in
      the 4 fps group. The dose area product (DAP), normalized DAP to body weight,
      total radiation time and fluoro time were lower in the 4 fps group but not
      statistically different than the 7.5 fps. The number of cine images and cine
      times were identical in both groups. Fluoroscopy and cineangiography contributed
      equally to radiation exposure. Fluoroscopy at 4 fps can be safe and effective for
      ASD device closure in children and adults. There was no increase in procedure
      time, cine time, fluoro time or complications at this slow fluoro rate. There was
      a trend toward decreased radiation exposure as measured by indexed DAP although
      not statistically significant in this small study. Further study with multiple
      operators using 4 fps fluoroscopy for simple interventional procedures is
      recommended.

PMID- 25618165
TI  - Age-related differences in human palatine tonsillar B cell subsets and
      immunoglobulin isotypes.
AB  - The tonsils provide defense of the upper aerodigestive tract against pathogens.
      Although long known to undergo functional changes with age, the precise changes
      occurring within tonsillar B cell populations remain undefined. In the present
      study, we investigated age-related changes in palatine tonsillar B cell subsets
      and immunoglobulin (Ig) isotypes. Palatine tonsils were obtained from forty-two
      tonsillectomy patients without tonsillitis who were divided into three groups:
      young children (4-9 years), adolescents (10-19 years), and adults (20-60 years).
      Tonsillar B cells were then analyzed by flow cytometry. Using expression of CD38
      and IgD to define B cell subsets, we found that the frequency of germinal center
      (GC) B cells in the tonsils was significantly higher, and the frequency of memory
      B cells lower, in young children as compared to adolescents and adults. Within
      the GC B cell subsets, adults had a higher frequency of IgA(+) cells and a lower
      frequency of IgM(+) cells as compared to individuals in the younger age groups.
      Moreover, young children had a higher frequency of IgG(+) cells in the GC B cell
      subsets than did individuals in the older age groups. We also observed an
      abundance of IgM(+) cells among memory B cells and plasmablasts in young children
      and IgA(+) cells in adults. In summary, the proportion of GC B cells in palatine
      tonsillar B cells decreases with age, while the proportion of memory B cells
      increases with age. In addition, Ig isotypes in tonsils preferentially switch
      from IgM to IgA as individuals age.

PMID- 25618166
TI  - In defense of (some) altered standards of care for Ebola infections in developed
      countries.
AB  - The current outbreak of Ebola virus infection in West Africa continues to spread.
      Several patients have now been treated in the United States and preparations are
      being made for more. Because of the strict isolation required for their care,
      questions have been raised about what diagnostic and therapeutic interventions
      should be available. I discuss the ethical challenges associated with caring for
      patients in strict isolation and personnel wearing bulky protective gear with
      reduced dexterity and flexibility, the limitations this may place on available
      treatments and the permissibility of consequent departures from the standards of
      care. Restricting access to some interventions such as surgery requiring an
      operating room, advanced imaging, etc. is reasonable due to concern for
      protecting other patients, visitors and staff. Cardiopulmonary resuscitation is a
      special case and the implications for withholding this intervention in situations
      where it may be desired is discussed, especially with respect to those patients
      who have suspected, but not proven, infection. These same restrictions are also
      considered under conditions where there are scarce resources and thus limited
      numbers of patients may receive care. While it is to be hoped that there is only
      limited and sporadic infection with Ebola virus in the US, careful thought must
      be given to the care of these patients under the unusual circumstances demanded
      by their isolation. I argue that an altered standard of care is reasonable and
      ethically acceptable under certain conditions. 

PMID- 25618167
TI  - Acute appendicitis revealing salpingiosis.

PMID- 25618168
TI  - Homeless Children and Their Families' Perspectives of Agency Services.
AB  - While numerous programs aim to mediate the risks for children experiencing
      homelessness, there is a lack of research representing the children's and
      parents' perspectives in supportive housing programs. With this phenomenological
      qualitative study, the authors share the voices of 22 participants, including
      children and their families, regarding their experiences while receiving services
      from a homeless agency. Participating parents perceived that the program provided
      resources to the children that they could not provide themselves, opportunities
      for exposure to positive new experiences, and improved psychosocial outcomes for
      their children. Participants also discussed desired program changes and the
      responsiveness of agency staff regarding unmet needs of the children.
      Implications for policies and programs are discussed. 

PMID- 25618169
TI  - Does Postgraduate Training in Community Mental Health Make a Difference to
      Primary Care Physicians' Attitudes to Depression and Schizophrenia?
AB  - This study investigated the differences in attitudes towards mental health
      patients between primary care physicians (PCPs) who have received postgraduate
      training in community mental health and those who have not. A questionnaire
      regarding the PCPs' attitudes towards mental health care in general, and
      specifically on depression and schizophrenia, was designed to compare the
      attitudes between the PCPs with postgraduate training in community mental health
      (CMH group) and those without (non-CMH group). Besides having greater confidence
      in management, PCPs in the CMH group had less stigmatizing opinions towards the
      mental health patients than those in the non-CMH group. Differences between the
      two groups were mostly shown in the case for depression but not for
      schizophrenia. The proportion of PCPs who liked to have depressed patients on
      their practice list was significantly higher in the CMH group (94 vs 71 %), and
      their satisfaction rate in looking after depressed patients was also
      significantly higher than the non-CMH group (87 vs 59 %). 

PMID- 25618170
TI  - Charles Lucas and medical legislation in eighteenth century Ireland.
AB  - INTRODUCTION: Charles Lucas, apothecary, physician and MP, was instrumental in
      facilitating legislation in Ireland in 1765 that established a nationwide network
      of hospitals in Ireland. This legislation was unique in contemporary Europe, and
      by the end of the century, there was a hospital in every county in the country.
      MATERIALS AND METHODS: His work as an apothecary provided him with the knowledge
      to attempt to address the problems in the apothecaries' trade, and his 1741
      pamphlet, Pharmacomastix, provided the framework for the 1761 Irish Apothecaries
      Act, which attempted to address these issues. It was, however, 1791 before
      nationwide regulation of the Irish apothecaries' trade was implemented following
      the establishment of the Apothecaries Hall, and this was 24 years before similar
      regulatory legislation was passed in Britain. Lucas sought enhanced regulation of
      the apothecaries' trade to provide better quality drugs and medicines for the
      general public, and he tried to ensure that untrained quacks did not practise as
      apothecaries, unbeknownst to their patients. He was aware that his proposals
      would meet with opposition, but he had the courage to pursue these without any
      element of personal gain. CONCLUSION: In medical terms, Charles Lucas was man
      ahead of his time.

PMID- 25618171
TI  - The Essay on waters and other medical writings of Charles Lucas.
AB  - In recent years, more attention has been given to Charles Lucas's medical career,
      in its own way just as interesting and important as his better-known political
      campaigns. Lucas's first concentrated period of medical activity was in the
      1730s, when he had qualified as an apothecary, the second in the 1750s, following
      his flight from Ireland and achievement of qualifications in medicine. Having
      been prominently involved in the campaign which led to the 1735 drugs regulation
      act, in 1741 Lucas published a pamphlet, Pharmacomastix, which detailed abuses
      common in the apothecary's trade and pressed for more radical controls. His most
      substantial medical work, An Essay on Waters, was published in London in 1756,
      being devoted to analysis of European spas and the promotion of hydrotherapy.
      Lucas was able to return to Ireland in 1761 and was elected MP for Dublin city.
      While politics occupied most of his time until his death in 1771, Lucas
      maintained his interest in matters medical, securing the passage of another drugs
      regulation act in 1761, which remarkably is still on the Irish statute book. 

PMID- 25618172
TI  - Driving under the influence of synthetic phenethylamines: a case series.
AB  - New psychoactive drugs, so-called legal highs, have gained more and more
      popularity during the last years. One of the most important groups of these legal
      high substances are the synthetic phenethylamines that share a common
      phenethylamine moiety. Based on certain structural characteristics, these
      synthetic phenethylamines can be divided into further subclasses, among which the
      synthetic cathinones ('bath salts') are particularly noteworthy. Synthetic
      cathinones are characterized by an additional carbonyl group attached at the beta
      position on the amino alkyl chain. Consumption of synthetic phenethylamines can
      lead to impairments similar to those observed after the use of, for instance,
      amphetamine or 3,4-methylenedioxy-N-methylamphetamine (MDMA, 'ecstasy'). These
      impairments include diverse neurological and psychological symptoms which can
      affect a safe driving behaviour. Although several reports on clinical symptoms
      and poisonings due to these substances have been published, most of these
      publications do not contain any analytical data. Additionally, there is still a
      lack of information concerning pharmacological and toxicological effects of these
      rather new psychoactive substances. In particular, the knowledge of the impact on
      the ability to drive following consumption of synthetic phenethylamines is
      relevant for the police as well as for forensic toxicologists. In this
      publication, several cases of individuals driving under the influence (DUI) of
      synthetic phenethylamines (4-fluoroamphetamine, mephedrone (4
      methylmethcathinone, 4-MMC), 2-DPMP (desoxypipradol), methylenedioxypyrovalerone
      (MDPV), benzedrone, N-ethylamphetamine (etilamfetamine), 3-methylmethcathinone (3
      MMC)) are presented, focusing on analytical results and signs of impairment. 

PMID- 25618173
TI  - The Clinical Evaluation of Tegafur Gimeracil Oteracil Combined with THP and DDP
      for Second-Line Treatment of Advanced Cardiac Carcinoma.
AB  - The aim of this study is to explore the clinical effect of tegafur gimeracil
      oteracil combined with pirarubicin hydrochloride (THP) and
      diamminedichloroplatinum (DDP) for second-line treatment of advanced cardiac
      carcinoma, and find the most effective method to improve its survival rate and
      decrease the adverse reactions. 70 patients with advanced cardiac carcinoma
      admitted during February 2010-March 2014 were selected and divided into two
      groups with 35 cases in each group. All patients were treated with THP and DDP,
      and tegafur gimeracil oteracil was added to the observation group. The
      differences of effective rate, life quality, and adverse reactions after
      treatment in observational group were observed. The result of total curative
      effect indicated that the occurrence rate of complete remission + partial
      remission (CR + PR) in the control group was 28.57 %, the total effective rate
      was 51.43 %, the occurrence rate of CR + PR in the observational group was 34.29
      %, and the total effective rate was 57.15 %; there was no statistical difference
      between the two groups (P > 0.05). The result of KPS scoring indicated that the
      improvement rate in the control group was 28.57 %, the total effective rate was
      62.86 %, the improvement rate in the observational group was 42.86 %, and the
      total effective rate was 80 %; there was statistical difference between two
      groups (P < 0.05); the occurrence rates of adverse reactions including leukocyte
      decrease, thrombocytopenia, anemia, nausea and vomiting, constipation, peripheral
      neurovirulence, hepatotoxicity, and renal toxicity were statistically different
      (P < 0.05). Tegafur gimeracil oteracil combined with THP and DDP in treating
      advanced cardiac carcinoma can improve the life quality and decrease the adverse
      reactions. 

PMID- 25618174
TI  - Transmission of Anaplasma phagocytophilum from endothelial cells to peripheral
      granulocytes in vitro under shear flow conditions.
AB  - Anaplasma phagocytophilum (Ap) is a tick-borne pathogen, which can cause
      granulocytic anaplasmosis in humans and animals. In vivo this obligate
      intracellular pathogen is primarily located in circulating mature granulocytes,
      but it also infects endothelial cells. In order to study the interaction between
      Ap-infected endothelial cells and human granulocytes under conditions similar to
      those found naturally in the infected host, an in vitro model that mimics
      physiological flow conditions in the microvasculature was established. Cell-to
      cell interactions were then visualized by microscopy, which showed that
      granulocytes adhered strongly to Ap-infected endothelial cells at a shear stress
      of 0.5 dyne/cm(2). In addition, Ap-transmission assays under flow conditions
      showed that the bacteria transferred from infected endothelial cells to
      circulating granulocytes and were able to establish infection in constantly
      moving granulocytes. Cell surface analysis showed that Ap induced up-regulation
      of the cell adhesion molecules ICAM-1 and VCAM-1 on infected endothelial cells in
      a dose-dependent manner. Furthermore, IL-8 secretion by endothelial cells
      indicated that the presence of Ap induced a pro-inflammatory response. In
      summary, the results of this study suggest that endothelial cells of the
      microvasculature (1) provide an excellent site for Ap dissemination to peripheral
      blood granulocytes under flow conditions and therefore may play a crucial role in
      the development of persistent infection, and (2) are stimulated by Ap to express
      surface molecules and cytokines that may lead to inflammatory responses at the
      site of the infection.

PMID- 25618176
TI  - [Give to Caesar what is Caesar's... The first modern obstetrical vacuum extractor
      is not Scandinavian but French! Tribute to Doctor Yves Couzigou (1910-1989)].

PMID- 25618175
TI  - Pain and difficulties performing valued life activities in women and men with
      rheumatoid arthritis.
AB  - This study aimed to examine the difficulties with performing valued life
      activities in relation to pain intensity in women and men with rheumatoid
      arthritis (RA). In total, 737 persons with RA (73 % women) from three
      rheumatology units in Sweden responded to a questionnaire measuring performance
      of 33 valued life activities and self-rated pain. The relationships between
      performance of valued life activities (VLAs) and pain (measured by visual
      analogue scale (VAS)) were analysed based on gender. Multiple linear regression
      analyses were conducted with the total VLA score as dependent variable. Women
      reported more pain and difficulties in performing valued life activities than
      men. Across genders, 85 % reported at least one valued life activity affected by
      RA. Significantly more women than men encountered difficulties in performing some
      activities such as cooking, gardening and meeting new people. Women reported
      higher pain intensity (35 mm) than men (31 mm). Almost all 33 difficulty ratings
      for valued life activities were higher among persons with high pain (>40 mm) than
      persons with lower pain. Difficulty ratings for valued life activities correlated
      positively with pain in persons with lower pain, but not among those with high
      pain. The results highlight the importance of addressing pain, especially among
      women with RA, as they reported pain to impact on their valued life activities.
      Interestingly, this was evident also in women with lower levels of pain.

PMID- 25618177
TI  - [ENTOG annual exchange program, Glasgow-Scotland, May 2014].

PMID- 25618178
TI  - [Using an ovarian drilling by hydrolaparoscopy or recombinant follicle
      stimulating hormone plus metformin to treat polycystic ovary syndrome: Why a
      randomized controlled trial fail?].
AB  - OBJECTIVES: To evaluate pregnancy rates after randomized controlled trial (RCT)
      between ovarian drilling by fertiloscopy or ovarian
      hyperstimulation+insemination+metformine after clomifene citrate (cc) treatment
      fails. PATIENTS AND METHODS: Randomized controlled trial with 126 patients in
      each arm in 9 university centers. After 6-9 months of stimulation by cc, 2 groups
      were randomized: group 1, ovarian drilling with bipolar energy versus group 2: 3
      months treatment by metformine followed by 3 hyperstimulation by
      FSH+insemination. The success rate was pregnancy rate above 12 weeks. RESULTS:
      RCT was stopped after the screening of 40 patients. In spite of the low number of
      patients, the pregnancy rate is significantly higher in medical group 8/16 versus
      3/18 (p=0.04). CONCLUSION: The causes of fail of RCT were in relationship with
      difficulties of inclusion, with absence of final agreement by team included.
      Moreover, RCT between medical and surgical management is often root of
      difficulties for patients who decline surgical strategy. However, medical
      treatment appeared better than drilling in this RCT.

PMID- 25618179
TI  - The expanding role of co-trimoxazole in developing countries.
AB  - Co-trimoxazole is an inexpensive, broad-spectrum antimicrobial drug that is
      widely used in developing countries. Before antiretroviral therapy (ART) scale
      up, co-trimoxazole prophylaxis reduced morbidity and mortality in adults and
      children with HIV by preventing bacterial infections, diarrhoea, malaria, and
      Pneumocystis jirovecii pneumonia, despite high levels of microbial resistance. Co
      trimoxazole prophylaxis reduces early mortality by 58% (95% CI 39-71) in adults
      starting ART. Co-trimoxazole provides ongoing protection against malaria and non
      malaria infections after immune reconstitution in ART-treated individuals in sub
      Saharan Africa, leading to a change in WHO guidelines, which now recommend long
      term co-trimoxazole prophylaxis for adults and children in settings with a high
      prevalence of malaria or severe bacterial infections. Co-trimoxazole prophylaxis
      is recommended for HIV-exposed infants from age 4-6 weeks; however, the risks and
      benefits of co-trimoxazole during infancy are unclear. Co-trimoxazole prophylaxis
      reduces anaemia and improves growth in children with HIV, possibly by reducing
      inflammation, either through direct immunomodulatory activity or through effects
      on the intestinal microbiota leading to reduced microbial translocation. Ongoing
      trials are now assessing the ability of adjunctive co-trimoxazole to reduce
      mortality in children after severe anaemia or severe acute malnutrition. In this
      Review, we discuss the mechanisms of action, benefits and risks, and clinical
      trials of co-trimoxazole in developing countries. 

PMID- 25618180
TI  - Stem cell therapy for inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) could be curable by "immune rest" and correction
      of the genetic predisposition inherent in allogeneic hematopoietic stem cell
      transplantation. However, balancing risks against benefits remains challenging.
      The application of mesenchymal stem cells (MSCs) serving as a site-regulated
      "drugstore" is a recent concept, which suggests the possibility of an alternative
      treatment for many intractable diseases such as IBD. Depending on the required
      function of MSC, such as a cell provider, immune moderator, and/or trophic
      resource, MSC therapy should be optimized to maximize its therapeutic benefit.
      Therapeutic effects do not always require full engraftment of MSCs. Therefore,
      optimization of pleiotropic gut trophic factors produced by MSCs, which favoring
      not only regulating immune responses but also promoting tissue repair, must
      directly enhance new drug discoveries for treatment of IBD. Stem cell biology
      holds great promise for a new era of cell-based therapy, sparking considerable
      interest among scientists, clinicians, and patients. However, the translational
      arm of stem cell science remains in a relatively primitive state. Although
      several clinical studies using MSCs have been initiated, early results suggest
      several inherent problems. In each study, optimization of MSC therapy appears to
      be the most urgent problem, and can be resolved only by scientifically unveiling
      the mechanisms of therapeutic action. In the present review, the authors outline
      how such information would facilitate the critical steps in the paradigm shift
      from basic research on stem cell biology to clinical practice of regenerative
      medicine for conquering IBD in the near future. 

PMID- 25618181
TI  - [Which is the role of cultures in the diagnosis of onychomycosis?].

PMID- 25618182
TI  - Disseminated cutaneous histoplasmosis in elderly patients. An uncommon
      presentation.

PMID- 25618183
TI  - Phenotypic characterization and adhesive properties of vaginal Candida spp.
      strains provided by the CHU Farhat Hached (Sousse, Tunisia).
AB  - BACKGROUND: Vulvovaginal candidiasis is a common infection among women worldwide,
      being Candida albicans the most commonly isolated species. Therefore, controlling
      this opportunistic yeast is one of the key factors for reducing nosocomial
      infection. AIMS: We investigated several virulence properties of 28 vaginal
      strains of Candida isolated from Tunisian women suffering from vulvovaginitis. We
      also analyzed the virulence properties of a clinical Candida krusei strain and
      five Candida reference strains. METHODS: Candida strains were subjected to
      microscopic analysis and culture in Candida ID2 chromogenic medium. The adhesive
      properties of these strains were estimated by the microtiter plate - the safranin
      staining - and the Congo red agar (CRA) methods, for determining yeast ability to
      form biofilms on biomaterials used in urinary catheter manufacturing. Their
      potency to produce hydrolytic enzymes was also studied. RESULTS: Our results
      showed that nine out of the total studied strains produced phospholipase. In
      addition, very high protease activity was detected in 23 Candida strains. All
      Candida strains were beta-hemolytic and adhered to polystyrene microtiter plates
      in varying degrees. Two vaginal C. albicans strains were strongly adhesive to
      polystyrene and glass slides. Also, our results showed that vaginal Candida
      strains were more adhesive to the three tested materials than the reference
      strains. CONCLUSIONS: This study shows the presence of a range of virulence and
      adhesion factors in clinical isolates of vaginal Candida. Consequently, control
      and treatment of vaginal candidiasis as a means to prevent biofilm formation on
      urinary catheters is of crucial importance.

PMID- 25618184
TI  - Enhanced production of lovastatin by Omphalotus olearius (DC.) Singer in solid
      state fermentation.
AB  - BACKGROUND: Although lovastatin production has been reported for different
      microorganism species, there is limited information about lovastatin production
      by basidiomycetes. AIMS: The optimization of culture parameters that enhances
      lovastatin production by Omphalotus olearius OBCC 2002 was investigated, using
      statistically based experimental designs under solid state fermentation. METHODS:
      The Plackett Burman design was used in the first step to test the relative
      importance of the variables affecting production of lovastatin. Amount and
      particle size of barley were identified as efficient variables. In the latter
      step, the interactive effects of selected efficient variables were studied with a
      full factorial design. RESULTS: A maximum lovastatin yield of 139.47mg/g
      substrate was achieved by the fermentation of 5g of barley, 1-2mm particle diam.,
      at 28 degrees C. CONCLUSIONS: This study showed that O. olearius OBCC 2002 has a
      high capacity for lovastatin production which could be enhanced by using solid
      state fermentation with novel and cost-effective substrates, such as barley.

PMID- 25618185
TI  - Adding measures of body composition to the CKD-EPI GFR estimating equation in
      Indigenous Australians: the eGFR study.

PMID- 25618187
TI  - Prevalence of hypercalcemia associated with rhabdomyolysis: a dual-center case
      series.

PMID- 25618188
TI  - Evaluation of Renal Blood Flow and Oxygenation in CKD Using Magnetic Resonance
      Imaging.
AB  - BACKGROUND: Animal studies suggest that progression of chronic kidney disease
      (CKD) is related to renal hypoxia. With renal blood supply determining oxygen
      delivery and sodium absorption being the main contributor to oxygen consumption,
      we describe the relationship between renal oxygenation, renal artery blood flow,
      and sodium absorption in patients with CKD and healthy controls. STUDY DESIGN:
      Cross-sectional study. SETTING & PARTICIPANTS: 62 stable patients with CKD stages
      3 to 4 (mean age, 61+/-13 [SD] years) and 24 age- and sex-matched controls.
      PREDICTORS: CKD versus control status. OUTCOMES: Renal artery blood flow, tissue
      oxygenation (relative changes in deoxyhemoglobin concentration of the renal
      medulla [MR2*] and cortex [CR2*]), and sodium absorption. MEASUREMENTS: Renal
      artery blood flow was determined by phase-contrast magnetic resonance imaging
      (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI.
      Ultrafiltered and reabsorbed sodium were determined from measured glomerular
      filtration rate (mGFR) and 24-hour urine collections. RESULTS: mGFR in patients
      was 37% that of controls (36+/-15 vs 97+/-23 mL/min/1.73 m(2); P < 0.001), and
      reabsorbed sodium was 37% that of controls (6.9 vs 19.1 mol/24 h; P < 0.001).
      Single-kidney patient renal artery blood flow was 72% that of controls (319 vs
      443 mL/min; P < 0.001). Glomerular filtration fraction was 9% in patients and 18%
      in controls (P < 0.001). Patients and controls had similar CR2* (13.4 vs 13.3 s(
      1)) and medullary MR2* (26.4 vs 26.5 s(-1)) values. Linear regression analysis
      demonstrated no associations between R2* and renal artery blood flow or sodium
      absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had
      very small effects on CR2*, but reduced MR2* in both groups. LIMITATIONS: Only
      renal artery blood flow was determined and thus regional perfusion could not be
      related to CR2* or MR2*. CONCLUSIONS: In CKD, reductions of mGFR and reabsorbed
      sodium are more than double that of renal artery blood flow, whereas cortical and
      medullary oxygenation are within the range of healthy persons. Reduction in
      glomerular filtration fraction may prevent renal hypoxia in CKD.

PMID- 25618186
TI  - Effect of ruboxistaurin on albuminuria and estimated GFR in people with diabetic
      peripheral neuropathy: results from a randomized trial.

PMID- 25618189
TI  - Hydrolysis of amphenicol and macrolide antibiotics: Chloramphenicol, florfenicol,
      spiramycin, and tylosin.
AB  - Antibiotics that enter the environment can present human and ecological health
      risks. An understanding of antibiotic hydrolysis rates is important for
      predicting their environmental persistence as biologically active contaminants.
      In this study, hydrolysis rates and Arrhenius constants were determined as a
      function of pH and temperature for two amphenicol (chloramphenicol and
      florfenicol) and two macrolide (spiramycin and tylosin) antibiotics. Antibiotic
      hydrolysis rates in pH 4-9 buffer solutions at 25 degrees C, 50 degrees C, and 60
      degrees C were quantified, and degradation products were characterized. All of
      the antibiotics tested remained stable and exhibited no observable hydrolysis
      under ambient conditions typical of aquatic ecosystems. Acid- and base-catalyzed
      hydrolysis occurred at elevated temperatures (50-60 degrees C), and hydrolysis
      rates increased considerably below pH 5 and above pH 8. Hydrolysis rates also
      increased approximately 1.5- to 2.9-fold for each 10 degrees C increase in
      temperature. Based on the degradation product masses found, the functional groups
      that underwent hydrolysis were alkyl fluoride, amide, and cyclic ester (lactone)
      moieties; some of the resultant degradation products may remain bioactive, but to
      a lesser extent than the parent compounds. The results of this research
      demonstrate that amphenicol and macrolide antibiotics persist in aquatic systems
      under ambient temperature and pH conditions typical of natural waters. Thus,
      these antibiotics may present a risk in aquatic ecosystems depending on the
      concentration present. 

PMID- 25618190
TI  - Application of biochar for the removal of pollutants from aqueous solutions.
AB  - In recent years, many studies have been devoted to investigate the application of
      biochar for pollutants removal from aqueous solutions. Biochar exhibits a great
      potential to efficiently tackle water contaminants considering the wide
      availability of feedstock, low-cost and favorable physical/chemical surface
      characteristics. This review provides an overview of biochar production
      technologies, biochar properties, and recent advances in the removal of heavy
      metals, organic pollutants and other inorganic pollutants using biochar.
      Experimental studies related to the adsorption behaviors of biochar toward
      various contaminants, key affecting factors and the underlying mechanisms
      proposed to explain the adsorption behaviors, have been comprehensively reviewed.
      Furthermore, research gaps and uncertainties that exist in the use of biochar as
      an adsorbent are identified. Further research needs for biochar and potential
      areas for future application of biochars are also proposed. 

PMID- 25618191
TI  - Polychlorinated biphenyl concentration changes in sewage sludge and organic
      municipal waste mixtures during composting and anaerobic digestion.
AB  - We determined the changes in polychlorinated biphenyl (PCB) concentrations in a
      mixture of sewage sludge and the organic fraction of municipal waste during
      composting and during anaerobic digestion. The processes were carried out on a
      laboratory scale. The PCBs were analyzed in the waste samples using gas
      chromatography-mass spectrometry. We evaluated the rates at which the PCB
      concentrations decreased during composting and during anaerobic digestion and
      compared the PCB degradation kinetics during these processes. The most important
      conclusion of this work is that anaerobic digestion is much more effective than
      composting at removing PCBs from a mixture of sewage sludge and the organic
      fraction of municipal waste. 

PMID- 25618192
TI  - An examination of the potential added value of water safety plans to the United
      States national drinking water legislation.
AB  - National and sub-national governments develop and enforce regulations to ensure
      the delivery of safe drinking water in the United States (US) and countries
      worldwide. However, periodic contamination events, waterborne endemic illness and
      outbreaks of waterborne disease still occur, illustrating that delivery of safe
      drinking water is not guaranteed. In this study, we examined the potential added
      value of a preventive risk management approach, specifically, water safety plans
      (WSPs), in the US in order to improve drinking water quality. We undertook a
      comparative analysis between US drinking water regulations and WSP steps to
      analyze the similarities and differences between them, and identify how WSPs
      might complement drinking water regulations in the US. Findings show that US
      drinking water regulations and WSP steps were aligned in the areas of describing
      the water supply system and defining monitoring and controls. However, gaps exist
      between US drinking water regulations and WSPs in the areas of team procedures
      and training, internal risk assessment and prioritization, and management
      procedures and plans. The study contributes to understanding both required and
      voluntary drinking water management practices in the US and how implementing
      water safety plans could benefit water systems to improve drinking water quality
      and human health. 

PMID- 25618193
TI  - Effect of prone positioning in mild to moderate obstructive sleep apnea syndrome.
AB  - BACKGROUND: Sleeping in prone position could be effective in the management of
      obstructive sleep apnea (OSA) syndrome by reducing the gravity effect on the
      upper airway and hence collapsibility. Effect of pure prone positioning (PPP)
      treatment was investigated in mild to moderate OSA. PATIENTS AND METHODS: Twenty
      nine mild to moderate OSA patients (17 males, 12 females) who gave informed
      consent were tested with polysomnography at diagnostic and PPP nights. PPP device
      consisted of a pillow mounted on a table with a hole in the middle keeping the
      neck 180 degrees  extended in prone position. Mean +/- SD of age and AHI were
      48.4 +/- 10.6 and 15.5 +/- 6.2, respectively. Patients did not have abdominal
      and/or truncalobesity, or any condition that could interfere with prone sleeping.
      RESULTS: AHI (mean difference: PPP treatment - diagnostic night: -5.2/h, 95%
      confidence interval [CI]: -0.1/h to -10.3/h, p = 0.04) and sleep oxygen
      saturation below 90% (mean difference: -1.80%, 95% CI: -0.22% to -3.37%, p =
      0.02) and sleep efficiency (81.0 +/- 21.2% and 88.1 +/- 7.1 %, respectively, p =
      0.02) were significantly lower in PPP than diagnostic night. Response to PPP
      treatment defined as AHI <5/h in the PPP night was observed in 15 (51.7%)
      patients, with a better rate in female than male patients (9/12 vs. 6/17,
      respectively, p = 0.03). CONCLUSIONS: To our knowledge, this is the first study
      to examine the effect of prone positioning in the treatment of mild to moderate
      OSA. Application of PPP with a more comfortable design in a randomized clinical
      trial is required to investigate its long term effect in the treatment of mild to
      moderate OSA.

PMID- 25618194
TI  - Identity, history, and education in Rwanda: Reflections on the 2014 Nobel Peace
      Prize.

PMID- 25618195
TI  - Patterns of maltreatment and diagnosis across levels of care in group homes.
AB  - Patterns of Axis I psychiatric diagnosis and maltreatment history were explored
      among youth in group homes, including match of clinical need to level or
      restrictiveness of care. Data on demographics, diagnoses, maltreatment, and group
      home level of care (Level I, II, or III homes, representing lower to higher
      intensity of supervision and treatment) were obtained from 523 youth who
      participated in a quasi-experimental study of group homes. Three quarters of
      youth had a diagnosis and two-thirds of youth had a maltreatment history. Youth
      in higher level homes had more diagnoses and higher rates of all disorders except
      adjustment disorders. Youth in Level I homes had a history of more maltreatment
      types, particularly high rates of neglect. Sexual abuse, physical abuse, and
      emotional abuse were most common among youth in higher level homes. Regardless of
      diagnosis history, comparable proportions of youth had a maltreatment history,
      and similar patterns were found across levels of care. Together, findings
      indicate that group homes with varying degrees of restrictiveness serve youth
      with different psychiatric diagnosis and maltreatment histories. Youth triaged to
      higher level homes had more diagnoses, while youth placed in the least
      restrictive homes had a history of more maltreatment subtypes. Further, distinct
      patterns of diagnosis types and maltreatment subtypes were seen across homes.
      Implications include the importance of assessing unique clinical needs of youth
      to promote an appropriate match to level of care and treatment plan. 

PMID- 25618196
TI  - Balance problems after traumatic brain injury.

PMID- 25618197
TI  - Cardiovascular comorbidities in obstructive sleep apnoea according to age: a
      sleep clinic population study.
AB  - PURPOSE: To describe the features of obstructive sleep apnoea (OSA) and its
      association with arterial hypertension (HT), coronary artery disease (CAD), and
      arrhythmias in elderly (>=65 years) versus younger patients. METHODS: All adult
      patients referred to our Sleep Research Unit for suspected OSA were included and
      underwent a thorough medical examination and an in-laboratory polysomnography.
      The severity of OSA was defined by the apnoea-hypopnoea index (AHI) as mild [5
      15/h), moderate [15-30/h), and severe (>=30/h). RESULTS: Elderly patients (n =
      136) and really old patients (>75 years) had higher prevalence of OSA (89 %) and
      severe OSA (36.8 %) as compared to younger patients (n = 439; 79.5 and 27.6 %,
      respectively, p < 0.05). In patients with OSA, the elderly group had a poorer
      sleep quality and more severe nocturnal oxygen desaturation than the younger
      group. Elderly patients presented higher percentages of HT (47.8 %), CAD (19.8
      %), and arrhythmias (16.2 %) as compared to younger patients (p < 0.01). The odds
      ratio (OR) for HT increased with OSA severity from 1.0 to 1.65 (95 % confidence
      interval 0.83-3.27), 1.0 to 2.5 (95 % CI 1.25-5.00), and 1.0 to 3.77 (1.95-7.29)
      in younger patients, but not in elderly ones where the OR increased from 1.0 to
      0.6 (0.17-2.04), 1.0 to 1.14 (0.34-3.82), and 1.0 to 1.46 (0.46-4.63),
      respectively. CONCLUSION: Stronger relation of HT and OSA severity in younger
      patients should encourage us to screen OSA in these patients at very young age.
      Increased OSA severity without obesity in very old patients needs to be confirmed
      and further studied.

PMID- 25618198
TI  - [The management of lung transplantation candidates. A case series].
AB  - INTRODUCTION: Lung transplantation (LT) is associated with an increased risk of
      infection, cancer, chronic renal failure, cardiovascular disease and
      osteoporosis. Some risk factors precede transplantation and could benefit for
      early diagnosis and optimised care. METHODS: The incidence of comorbidities and
      their treatment before referral were assessed in 157 consecutive lung transplant
      candidates between 2008 and 2011. RESULTS: The median age was 37years [25; 51].
      Fifty-six percent had a body mass index below 19kg/m(2). In the COPD group, only
      50 % had undergone a pulmonary rehabilitation program in the preceding 2 years.
      Osteoporosis was present in 42 %, of whom 36 % were on bisphophonate therapy.
      Vitamin D deficiency was present in 65 %. Previously undiagnosed cardiovascular
      risk factors were discovered during LT assessment: hypertension in one patient,
      hypercholesterolemia in 6 % and diabetes in 4 %. Poor dental condition
      necessitating extractions were found in 41 % of patients. Protective anti-HBs
      antibodies levels were present in 50 % of the patients at the time of referral.
      CONCLUSION: The assessment and early treatment of nutritional disorders,
      osteoporosis and risk factors for infection as well as addressing associated
      cardiovascular risk factors should be optimised in the care of patients with
      chronic respiratory insufficiency. The potential for becoming a lung transplant
      candidate in the future should be kept in mind early in the global management of
      those patients.

PMID- 25618199
TI  - [Deliberate interruptions and changes of dose of inhaled corticosteroids by
      asthma patients: "a community pharmacy study"].
AB  - BACKGROUND: Adherence to inhaled corticosteroids (ICS) remains a major issue for
      asthma management, even among patients receiving a regular prescription from
      their doctor. The frequency of deliberate interruption of ICS, and of spontaneous
      changes of dose, were studied in a population of asthma patients recruited in
      community pharmacies. METHODS: Asthma patients (aged 18-50) recruited in
      community pharmacies reported in self-administered questionnaires their
      spontaneous interruptions and changes of doses of ICS during the past 3 months.
      The characteristics of patients who interrupted their therapy or who modified the
      dose were compared with other patients. RESULTS: The studied population included
      252 patients (mean age 35 year-old, females: 59%), of whom 62% had inadequately
      controlled asthma. Among these patients, 25% had interrupted ICS therapy during
      the past 3 months, while 21% spontaneously changed the dose. The most reported
      reason for interrupting ICS was the cessation of symptoms (50%). In multivariate
      analysis, interrupting ICS was mainly associated with inadequate asthma control
      (OR=3.1, 95% CI 1.5-6.4), while the strongest association with changing ICS doses
      was the patients' perception of asthma as a concern in their lives (OR=3.2, 95%
      CI 1.2-8.4). CONCLUSION: These results underline a poor understanding of the
      purpose of ICS therapy by patients. They also highlight the need of therapeutic
      education to improve the management of the disease.

PMID- 25618200
TI  - [Attitude of private pharmacists in the dispensation of asthma drugs].
AB  - INTRODUCTION: Despite recommendations, asthma remains poorly controlled in many
      countries. Asthmatic patients see pharmacy staff regularly to obtain medications.
      The aim of this study was to evaluate the attitude of pharmacists in Burkina Faso
      about dispensing asthma drugs. METHOD: A self-administered anonymous
      questionnaire was used to collect data in a descriptive cross-sectional study
      related to pharmacists' attitudes in the management of asthma in the city of
      Ouagadougou (November 2010-June 2011). RESULTS: The rate of participation of
      pharmacists in the study was 82.4%. Of the pharmacists surveyed, 70.1% reported
      having received asthma patients both during acute asthma exacerbations and when
      stable. Only 9% of pharmacists insisted on a prescription when asthma patients
      came to the pharmacy without one. A total of 73.6% of pharmacists explained and
      demonstrated how to use the spray to the patients. Among pharmacists who
      demonstrated how to use devices, only 6.7% actually checked patients' technique.
      Inhaler technique demonstration was done verbally in 68.8% of case. Among
      pharmacists, 34.5% reported a good mastery of inhaler techniques. CONCLUSION: The
      techniques for dispensing asthma drugs are not well established among pharmacists
      and therefore the provision of continuous medical education to pharmacists is
      important.

PMID- 25618201
TI  - [Sensitization to Blomia tropicalis among asthmatic patients in Yaounde,
      Cameroon].
AB  - INTRODUCTION: The aim of this study was to determine the prevalence and
      investigate associated factors for Blomia tropicalis (BT) sensitization in
      adolescent and adult patients with asthma in Yaounde (Cameroon). METHODS: We
      performed a cross-sectional study of 18 months duration (January 2012 to June
      2013). All asthmatic patients who were seen for a consultation during the study
      period and who had a skin prick testing for perennial aeroallergens were included
      in the study. RESULTS: Two hundred and one asthmatic patients (132 female
      patients, 65.7%) with median age (1st-3rd quartiles) of 35 (20-51.5) years were
      included in the study. Ninety-six (47.8%) patients had positive skin tests to BT.
      BT sensitization was associated with sensitization to two other dust mites
      (Dermatophagoides pteronyssinus [DP] and Dermatophagoides farinae [DF]) in 75
      (86.2%) patients. The only clinical factor associated with BT sensitization was
      the presence of persistent rhinitis (odds ratio [confidence interval 95%]: 2.06
      [1.12-3.81]). The independent allergenic factors associated with BT sensitization
      were sensitization to DP (3.49 [CI 95%: 1.49-8.19]), to DF (4.88 [CI 95%: 2.10
      11.36]) and to German cockroach (4.16 [CI 95%: 1.72-10.09]). CONCLUSION: Blomia
      tropicalis sensitization is common in asthmatic patients in Yaounde. It occurs
      most often in the context of sensitization to multiple aeroallergens,
      particularly with sensitization to other dust mites and German cockroach.

PMID- 25618202
TI  - [Early detection of COPD in occupational medicine in the Alpes-Maritimes].
AB  - INTRODUCTION: This study evaluated a standardized procedure aiming at early
      detection of COPD in a consecutive population of employees visiting occupational
      medicine. METHODS: A total of 2818 employees were included by 22 occupational
      physicians in 5 centers. Respiratory symptoms, smoking status, occupational
      exposures and socioprofessional categories were collected. Subjects with at least
      one symptom and/or risk factor underwent spirometry. RESULTS: In this population
      aged 39+/-12 years, 2603 patients were free of known asthma or COPD. The presence
      of at least one symptom was observed in 23.6 % of employees and was significantly
      associated with smoking status, occupational exposure to organic dust, gas fumes
      and vapors, and agriculture (P<0.0001). Airflow obstruction (FEV1/FVC < 0.70) was
      detected in 1.7 % of 1605 employees who underwent spirometry. With the inclusion
      of known COPD subjects (n=22), the prevalence reached 2.38 %. COPD was
      significantly associated with smoking intensity. Information on subsequent
      diagnosis was obtained in only two cases. The quality of spirometry was
      inadequate in 30 % of cases. Thirty-three percent of detected COPD subjects did
      not report any respiratory symptoms. CONCLUSION: The strategy used in this study
      (specific questionnaire plus spirometry) allowed detection of a few cases of
      previously undiagnosed COPD. Occupational physicians need specific training in
      spirometry and a better follow-up of care pathways is required to obtain
      diagnostic confirmation.

PMID- 25618203
TI  - [Clinical manifestations in patients exposed to an environmental toxic accident
      (Abidjan, Ivory Coast 2006)].
AB  - INTRODUCTION: In 2006, 528 tons of petroleum toxic waste have been released in
      Abidjan (Ivory Coast) during a major environmental accident. This study was aimed
      to describe the clinical manifestations provoked by these toxic waste. METHODS:
      We have analysed the records of patients admitted to the university hospital of
      Cocody (Abidjan) following exposure to toxic waste. All the information were
      recorded on specific files or on notification files created by the physicians of
      the National Institute of Public Health, the authority charged with the
      supervision of this exercise. The files were completed by the physician in the
      course of the examination of the patient. RESULTS: Over a period of 3-month
      period, 10,598 patients were examined. The clinical manifestations affected all
      age groups. They were dominated by respiratory symptoms: pulmonary (74.5%) and
      upper respiratory (31.0%). Pulmonary symptoms included cough (48.8%), chest pain
      (37.9%), dyspnoea (9.5%) and a few cases of hemoptysis. Digestive symptoms mainly
      comprised abdominal pain (36.2%), diarrhea (23.0%), abdominal distension (19.9%)
      and vomiting (9.9%). The other symptoms were neurological, ophthalmic,
      cardiovascular and gynaecological. More than 96% of patients presented with at
      least two symptoms. The respiratory symptoms were significantly more frequent in
      patients over the age of 17 while diarrhea and vomiting were more often found in
      patients less than 17 years old. Chest pain was significantly more common in men
      while abdominal pain and vomiting predominated in women (P=0.001). CONCLUSION:
      The clinical consequences of toxic waste exposure were varied and sometimes
      serious. A medium- and long-term evaluation of the subjects is required.

PMID- 25618204
TI  - [Fixed drug eruption after taking ethambutol].
AB  - INTRODUCTION: Fixed drug eruption (FDE) is a specific skin reaction and the only
      exclusively medicinal dermatosis. Among the drugs usually responsible are the
      antituberculous antibiotics including rifampicin and, less often, isoniazid and
      pyrazinamide. FDE after taking ethambutol is rarely described. CASE REPORT: A 32
      year old HIV negative patient presented a FDE localized to the internal surface
      of the lips and the interdigital folds during the 4th month of antituberculous
      treatment comprising rifampicin, isoniazid and ethambutol. The diagnosis was
      supported by the characteristic appearances of the lesions of FDE and their early
      reappearance in the same areas after accidental reintroduction of antituberculous
      triple therapy including ethambutol. Double-agent therapy with rifamicin and
      isoniazid was tolerated well. CONCLUSION: Discovery of FDE requires a rigorous
      search for the responsible medicine. During antituberculous treatment, the
      practitioner has to bear in mind the potential role of ethambutol, which is
      possibly potentiated by rifampicin.

PMID- 25618205
TI  - [Severe hyponatremia during chemotherapy for small cell carcinoma].
AB  - INTRODUCTION: The small cell lung cancer (SCLC) is a rapidly progressive
      malignancy with a poor prognosis. Its chemosensitivity mandates prompt treatment.
      Hyponatremia occurs frequently in patients with small cell lung cancer due to the
      syndrome of inappropriate antidiuretic hormone (SIADH). We report a case of
      severe hyponatremia induced by chemotherapy that required management in intensive
      care. OBSERVATION: A 68-year-old patient was undergoing treatment for small cell
      cancer, invading the right lung. On the second day of the first cycle of
      treatment (cisplatine-vepeside), the patient became comatose and required
      transfer to an intensive care unit. The coma was due to severe hyponatremia (107
      mmol/L) and improved with specific treatment. The patient had similar episodes on
      the second day of each chemotherapy treatment but with less and less severe
      clinical manifestations. Hyponatremia due to chemotherapy in SCLC is not commonly
      known; a relation between hyponatremia intensity and the tumor size is suspected.
      CONCLUSION: This clinical case highlights the possibility of severe hyponatremia
      during small cell lung cancer chemotherapy. Hyponatremia may be related to the
      reduction in tumor size. Monitoring of electrolytes on day 2 of chemotherapy is
      advised.

PMID- 25618206
TI  - [Unilateral transudative pleural effusion and constritive pericarditis].
AB  - INTRODUCTION: Constrictive pericarditis is associated with thickening, fibrosis
      or inflammation of the pericardium which can lead to signs of right ventricle
      dysfunction. It is usually a chronic process which can present in a variety of
      ways. We present two cases of constrictive pericarditis discovered during the
      investigation of a left-sided pleural effusion. OBSERVATION: The cases represent
      two sorts of constrictive pericarditis, chronic and due to pericardial effusions.
      Their common feature was an increase in dyspnoea and a new pleural effusion on
      the left side. Their difference lies in the presence of a thickened calcified
      pericardium in one case and the presence of a pericardial effusion in the other.
      In both cases, non-invasive investigation failed to diagnose any cardiac disease.
      The presence of constrictive pericarditis was confirmed by right heart
      catheterization. Treatment by subtotal pericardectomy was effective. CONCLUSION:
      The thoracic manifestations of constrictive pericarditis are most commonly
      recurring bilateral pleural effusions. The mode of presentation may be an
      exudative, or transudative effusion. Unilateral pleural involvement, fibrosis,
      chylothorax or tumour like presentations may occur. A diagnosis of constrictive
      pericarditis should be considered in these clinical contexts and an examination
      of the pericardium performed. Cardiac catheterization can help in the
      differential diagnosis.

PMID- 25618207
TI  - [Assessment of a tool for decision making in case of worsening condition of
      cancer patients].
AB  - BACKGROUND: In response to questions regarding the appropriate intensity of care
      for some patients, "a decision support aid regarding the intensity of care in
      case of worsening condition of a patient with a chronic disease" has been
      established at the Grenoble university hospital. According to patient's wishes
      and the experience of the medical and paramedical team who are responsible for
      him, a level of intensity of care will be suggested. METHODS: We propose a
      prospective and multicenter study conducted in the Rhone-Alpes-Auvergne area. All
      lung cancer patients admitted to a pulmonology unit in 2014 would be included.
      This document would be used if a decision to withhold life-sustaining treatment
      exists. We would assess the relationship between the planned intensity of care
      and those established when the patient develops organ failure. Patient
      characteristics and factors associated with proposed levels and types of care
      would be analyzed. Patient and family opinions will be obtained at 3 months. The
      number of subjects to be included is 468. EXPECTED RESULTS: Therefore, we hope to
      be able to define the wishes of patients' and to propose an appropriate and
      adapted aid for decisions if they develop organ failure.

PMID- 25618208
TI  - [Asymptomatic tracheobronchial nodules].

PMID- 25618209
TI  - [A mediastinal mass].

PMID- 25618210
TI  - [A misleading abscess mass].

PMID- 25618211
TI  - [Dasatinib-related pneumonia? An example of pharmacovigilance survey].

PMID- 25618213
TI  - Comorbidity predicts poor prognosis in nasopharyngeal carcinoma: development and
      validation of a predictive score model.
AB  - BACKGROUND AND PURPOSE: The impact of comorbidity on prognosis in nasopharyngeal
      carcinoma (NPC) is poorly characterized. MATERIAL AND METHODS: Using the Adult
      Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of
      comorbidity and developed, validated and confirmed a predictive score model in a
      training set (n=658), internal validation set (n=658) and independent set (n=652)
      using area under the receiver operating curve analysis. RESULTS: Comorbidity was
      present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%).
      Compared to an ACE-27 score ?1, patients with an ACE-27 score >1 in the training
      set had shorter overall survival (OS) and disease-free survival (DFS) (both
      P<0.001), similar results were obtained in the other sets (P<0.05). In
      multivariate analysis, ACE-27 score was a significant independent prognostic
      factor for OS and DFS. The combined risk score model including ACE-27 had
      superior prognostic value to TNM stage alone in the internal validation set (0.70
      vs. 0.66; P=0.02), independent set (0.73 vs. 0.67; P=0.002) and all patients
      (0.71 vs. 0.67; P<0.001). CONCLUSIONS: Comorbidity significantly affects
      prognosis, especially in stages II and III, and should be incorporated into the
      TNM staging system for NPC. Assessment of comorbidity may improve outcome
      prediction and help tailor individualized treatment.

PMID- 25618214
TI  - Comments regarding the positive review of "A Dictionary of Epidemiology".

PMID- 25618212
TI  - Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder.
AB  - Autism spectrum disorder (ASD) is characterized by high rates of comorbid
      internalizing and externalizing disorders. One mechanistic account of these
      comorbidities is that ASD is characterized by impaired emotion regulation (ER)
      that results in deficits modulating emotional responses. We assessed neural
      activation during cognitive reappraisal of faces in high functioning adults with
      ASD. Groups did not differ in looking time, pupilometry, or subjective ratings of
      faces during reappraisal. However, instructions to increase positive and negative
      emotional responses resulted in less increase in nucleus accumbens and amygdala
      activations (respectively) in the ASD group, and both regulation instructions
      resulted in less change in dorsolateral prefrontal cortex activation in the ASD
      group. Results suggest a potential mechanistic account of impaired ER in ASD. 

PMID- 25618215
TI  - Development and validation of an open source quantification tool for DSC-MRI
      studies.
AB  - MOTIVATION: This work presents the development of an open source tool for the
      quantification of dynamic susceptibility-weighted contrast-enhanced (DSC)
      perfusion studies. The development of this tool is motivated by the lack of open
      source tools implemented on open platforms to allow external developers to
      implement their own quantification methods easily and without the need of paying
      for a development license. MATERIALS AND METHODS: This quantification tool was
      developed as a plugin for the ImageJ image analysis platform using the Java
      programming language. A modular approach was used in the implementation of the
      components, in such a way that the addition of new methods can be done without
      breaking any of the existing functionalities. For the validation process, images
      from seven patients with brain tumors were acquired and quantified with the
      presented tool and with a widely used clinical software package. The resulting
      perfusion parameters were then compared. RESULTS: Perfusion parameters and the
      corresponding parametric images were obtained. When no gamma-fitting is used, an
      excellent agreement with the tool used as a gold-standard was obtained (R(2)>0.8
      and values are within 95% CI limits in Bland-Altman plots). CONCLUSION: An open
      source tool that performs quantification of perfusion studies using magnetic
      resonance imaging has been developed and validated using a clinical software
      package. It works as an ImageJ plugin and the source code has been published with
      an open source license.

PMID- 25618217
TI  - The role of real-time in biomedical science: a meta-analysis on computational
      complexity, delay and speedup.
AB  - PURPOSE: The concept of real-time is very important, as it deals with the
      realizability of computer based health care systems. METHOD: In this paper we
      review biomedical real-time systems with a meta-analysis on computational
      complexity (CC), delay (Delta) and speedup (Sp). RESULTS: During the review we
      found that, in the majority of papers, the term real-time is part of the thesis
      indicating that a proposed system or algorithm is practical. However, these
      papers were not considered for detailed scrutiny. Our detailed analysis focused
      on papers which support their claim of achieving real-time, with a discussion on
      CC or Sp. These papers were analyzed in terms of processing system used,
      application area (AA), CC, Delta, Sp, implementation/algorithm (I/A) and
      competition. CONCLUSIONS: The results show that the ideas of parallel processing
      and algorithm delay were only recently introduced and journal papers focus more
      on Algorithm (A) development than on implementation (I). Most authors compete on
      big O notation (O) and processing time (PT). Based on these results, we adopt the
      position that the concept of real-time will continue to play an important role in
      biomedical systems design. We predict that parallel processing considerations,
      such as Sp and algorithm scaling, will become more important.

PMID- 25618216
TI  - Representing and extracting lung cancer study metadata: study objective and study
      design.
AB  - This paper describes the information retrieval step in Casama (Contextualized
      Semantic Maps), a project that summarizes and contextualizes current research
      papers on driver mutations in non-small cell lung cancer. Casama's representation
      of lung cancer studies aims to capture elements that will assist an end-user in
      retrieving studies and, importantly, judging their strength. This paper focuses
      on two types of study metadata: study objective and study design. 430 abstracts
      on EGFR and ALK mutations in lung cancer were annotated manually. Casama's
      support vector machine (SVM) automatically classified the abstracts by study
      objective with as much as 129% higher F-scores compared to PubMed's built-in
      filters. A second SVM classified the abstracts by epidemiological study design,
      suggesting strength of evidence at a more granular level than in previous work.
      The classification results and the top features determined by the classifiers
      suggest that this scheme would be generalizable to other mutations in lung
      cancer, as well as studies on driver mutations in other cancer domains. 

PMID- 25618218
TI  - Clinical significance of IPF% or RP% measurement in distinguishing primary immune
      thrombocytopenia from aplastic thrombocytopenic disorders.
AB  - The diagnosis of primary immune thrombocytopenia (ITP) is based on differential
      diagnosis. Although the measurement of percentages of reticulated platelets (RP%)
      by flow cytometry is useful as a supportive diagnostic test, this method is
      nonetheless a time-consuming, laboratory-based assay. To identify alternative
      assays that are useful in daily practice, we compared three methods in parallel,
      IPF% measured by XE-2100 [IPF% (XE), Sysmex Corp.], IPF% measured by new XN-1000
      [IPF% (XN)], and RP%. We examined 47 patients with primary ITP, 28 patients with
      aplastic thrombocytopenia (18 aplastic anemia and 10 chemotherapy-induced
      thrombocytopenia) and 80 healthy controls. In a selected experiment, we examined
      16 patients with paroxysmal nocturnal hemoglobinuria (PNH) to examine the effect
      of hemolysis. As compared with IPF% (XE), IPF% (XN) showed better within-run
      reproducibility. The sensitivity and specificity for the diagnosis of ITP were
      83.0 and 75.0 % for IPF% (XE), 85.1 and 89.3 % for IPF% (XN), and 93.6 and 89.3 %
      for RP%, respectively. Examination of PNH patients revealed that hemolysis and/or
      red blood cell fragments interfered with IPF% (XE) values, but not with IFP %
      (XN) values. Our results suggest that IPF% measured by XN-1000 may be of
      comparable value with RP% as a supportive diagnostic test for ITP. 

PMID- 25618219
TI  - TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on
      efficacy and toxicity.
AB  - Recent studies have shown that the range of affinities of T cell receptors (TCRs)
      against non-mutated cancer peptide/class I complexes are lower than TCR
      affinities for foreign antigens. Raising the affinity of TCRs for optimal
      activity of CD8 T cells, and for recruitment of CD4 T cell activity against a
      class I antigen, provides opportunities for more robust adoptive T cell
      therapies. However, TCRs with enhanced affinities also risk increased reactivity
      with structurally related self-peptides, and off-target toxicities. Careful
      selection of tumor peptide antigens, in silico proteome screens, and in vitro
      peptide specificity assays will be important in the development of the most
      effective, safe TCR-based adoptive therapies. 

PMID- 25618220
TI  - Data dependent random forest applied to screening for laryngeal disorders through
      analysis of sustained phonation: acoustic versus contact microphone.
AB  - Comprehensive evaluation of results obtained using acoustic and contact
      microphones in screening for laryngeal disorders through analysis of sustained
      phonation is the main objective of this study. Aiming to obtain a versatile
      characterization of voice samples recorded using microphones of both types, 14
      different sets of features are extracted and used to build an accurate classifier
      to distinguish between normal and pathological cases. We propose a new, data
      dependent random forests-based, way to combine information available from the
      different feature sets. An approach to exploring data and decisions made by a
      random forest is also presented. Experimental investigations using a mixed gender
      database of 273 subjects have shown that the perceptual linear predictive
      cepstral coefficients (PLPCC) was the best feature set for both microphones.
      However, the linear predictive coefficients (LPC) and linear predictive cosine
      transform coefficients (LPCTC) exhibited good performance in the acoustic
      microphone case only. Models designed using the acoustic microphone data
      significantly outperformed the ones built using data recorded by the contact
      microphone. The contact microphone did not bring any additional information
      useful for the classification. The proposed data dependent random forest
      significantly outperformed the traditional random forest.

PMID- 25618221
TI  - Development and validation of an accelerometer-based method for quantifying gait
      events.
AB  - An original signal processing algorithm is presented to automatically extract, on
      a stride-by-stride basis, four consecutive fundamental events of walking, heel
      strike (HS), toe strike (TS), heel-off (HO), and toe-off (TO), from wireless
      accelerometers applied to the right and left foot. First, the signals recorded
      from heel and toe three-axis accelerometers are segmented providing heel and toe
      flat phases. Then, the four gait events are defined from these flat phases. The
      accelerometer-based event identification was validated in seven healthy
      volunteers and a total of 247 trials against reference data provided by a force
      plate, a kinematic 3D analysis system, and video camera. HS, TS, HO, and TO were
      detected with a temporal accuracy +/- precision of 1.3 ms +/- 7.2 ms, -4.2 ms +/-
      10.9 ms, -3.7 ms +/- 14.5 ms, and -1.8 ms +/- 11.8 ms, respectively, with the
      associated 95% confidence intervals ranging from -6.3 ms to 2.2 ms. It is
      concluded that the developed accelerometer-based method can accurately and
      precisely detect HS, TS, HO, and TO, and could thus be used for the ambulatory
      monitoring of gait features computed from these events when measured concurrently
      in both feet.

PMID- 25618222
TI  - The Spanish Society of Neurology's official clinical practice guidelines for
      epilepsy. Special considerations in epilepsy: comorbidities, women of
      childbearing age, and elderly patients.
AB  - INTRODUCTION: The characteristics of some population groups (patients with
      comorbidities, women of childbearing age, the elderly) may limit epilepsy
      management. Antiepileptic treatment in these patients may require adjustments.
      DEVELOPMENT: We searched articles in Pubmed, clinical practice guidelines for
      epilepsy, and recommendations by the most relevant medical societies regarding
      epilepsy in special situations (patients with comorbidities, women of
      childbearing age, the elderly). Evidence and recommendations are classified
      according to the prognostic criteria of Oxford Centre of Evidence-Based Medicine
      (2001) and the European Federation of Neurological Societies (2004) for
      therapeutic interventions. CONCLUSIONS: Epilepsy treatment in special cases of
      comorbidities must be selected properly to improve efficacy with the fewest side
      effects. Adjusting antiepileptic medication and/or hormone therapy is necessary
      for proper seizure management in catamenial epilepsy. Exposure to antiepileptic
      drugs (AED) during pregnancy increases the risk of birth defects and may affect
      fetal growth and/or cognitive development. Postpartum breastfeeding is
      recommended, with monitoring for adverse effects if sedative AEDs are used.
      Finally, the elderly are prone to epilepsy, and diagnostic and treatment
      characteristics in this group differ from those of other age groups. Although
      therapeutic limitations may be more frequent in older patients due to
      comorbidities, they usually respond better to lower doses of AEDs than do other
      age groups.

PMID- 25618223
TI  - Cytologic evaluation of cervical lymph node metastases from cancers of unknown
      primary origin.
AB  - Fine-needle aspiration biopsy (FNAB) is often the first diagnostic procedure
      performed in patients with head and neck (HN) masses. Metastatic squamous cell
      carcinoma (SCC) to cervical lymph nodes is by far the most common malignancy
      aspirated in the HN, but in approximately 3-10% of patients, a primary tumor will
      not be found even after complete clinico-radiological workup. Several HN cancers
      are associated with oncogenic viruses, including HPV-associated SCC and EBV
      associated nasopharyngeal carcinoma (NPC). While the primary tumor is sometimes
      small or undetectable, patients often present initially with cervical lymph node
      metastases. HPV-associated SCC and EBV-associated NPC are typically non
      keratinizing carcinomas that can mimic several other poorly differentiated HN
      cancers by FNAB but have a significantly better prognosis. Therefore, the precise
      classification of the metastatic disease in the FNAB material is very useful
      since it can facilitate the subsequent location of the primary tumor, and it can
      provide prognostic and therapeutic information as well. In this review, we
      discuss the major entities that can present as a metastatic cancer of unknown
      primary in cervical lymph node other than supraclavicular, including their
      cytologic features and the role of ancillary studies. 

PMID- 25618225
TI  - In controlling diabetes and obesity, employers have opportunities.

PMID- 25618224
TI  - Fracture incidence in pre- and postmenopausal women after completion of adjuvant
      hormonal therapy for breast cancer.
AB  - INTRODUCTION: Although the effect of hormonal therapy (HT) on fracture risk
      during treatment of breast cancer is established, information about fracture
      incidence after completion of HT is scarce. In this hospital based observational
      study we evaluated fracture rates after completion of HT in pre- and
      postmenopausal women with breast cancer. METHODS: All women diagnosed with breast
      cancer in the VieCuri Medical Center between 1998 and 2005 who started adjuvant
      HT with aromatase inhibitors or tamoxifen were included (n = 289). Data on
      fracture rate, fracture type and risk factors for fracture after completion of HT
      were collected. RESULTS: The overall fracture rate was 12% in pre- and 15% in
      postmenopausal women respectively during an average follow-up of 3.1 +/- 2.9
      years. The number of patients with at least one fracture was 41 (14%). There was
      no difference in fracture rates between different types of HT (P = 0.15). The
      most common types of fractures were toe/finger fractures in premenopausal- and
      hip and major fractures in postmenopausal women. Median time to first fracture
      was shorter in premenopausal women (1.4 years, IQR 0.2-3.5) than in
      postmenopausal women (2.4 years, IQR 0.7-5.1, P = 0.01). A history of previous
      fracture was a significant risk factor for fracture in postmenopausal women (HR
      3.9, 95% CI 1.3-11.7). CONCLUSION: Fracture rates in the first years after
      cessation of HT for breast cancer were 12% and 15% for pre- and postmenopausal
      women respectively. The most common fractures in postmenopausal women were hip
      and major fractures.

PMID- 25618226
TI  - Nonincretin drugs in later-stage development.

PMID- 25618227
TI  - Understanding the role of big data in the CV risk calculator controversy.

PMID- 25618228
TI  - Attacking complications to kidney problems in diabetes: atrial fibrillation and
      resistant hypertension.

PMID- 25618229
TI  - Dietary guidelines panel to take input from public.

PMID- 25618230
TI  - The JNC 8 hypertension guidelines: an in-depth guide.

PMID- 25618231
TI  - Nutritional supplements and cardiovascular health.

PMID- 25618232
TI  - Dangerous liaisons: obesity and diabetes.

PMID- 25618233
TI  - Temporal variability of radon in a remediated tailing of uranium ore processing-
      the case of Urgeirica (central Portugal).
AB  - Radon monitoring at different levels of the cover of the Urgeirica tailings shows
      that the sealing is effective and performing as desired in terms of containing
      the strongly radioactive waste resulting from uranium ore processing. However,
      the analysis of the time series of radon concentration shows a very complex
      temporal structure, particularly at depth, including very large and fast
      variations from a few tens of kBq m(-3) to more than a million kBq m(-3) in less
      than one day. The diurnal variability is strongly asymmetric, peaking at 18 h/19
      h and decreasing very fast around 21 h/22 h. The analysis is performed for summer
      and for a period with no rain in order to avoid the potential influence of
      precipitation and related environmental conditions on the radon variability.
      Analysis of ancillary measurements of temperature, relative humidity, wind speed
      and wind direction, as well as atmospheric pressure reanalysis data shows that
      the daily averaged radon concentration in the taillings material is anti
      correlated with the atmospheric pressure and that the diurnal amplitude is
      associated with the magnitude of atmospheric pressure daily oscillations.

PMID- 25618234
TI  - Molecular analysis and susceptibility pattern of meticillin-resistant
      Staphylococcus aureus strains in emergency department patients and related risk
      factors in Iran.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) has become
      widespread in the hospital and in the community. Nasal colonization with MRSA has
      been identified as a risk factor for MRSA infection. AIM: To determine the
      prevalence of nasal colonization with MRSA among adult patients in the emergency
      department (ED) by considering the risk factors for MRSA carriage and antibiotic
      susceptibility patterns. METHODS: A cross-sectional study was conducted among 810
      patients in the ED in Kashan, Iran. A questionnaire concerning the risk factors
      for MRSA colonization was completed for each patient. Specimens were obtained
      from the anterior nares. A multiplex polymerase chain reaction (PCR) assay was
      used for SCCmec typing, and a PCR assay was used to detect Panton-Valentine
      leukocidin (PVL) genes. MRSA susceptibility to amikacin, clindamycin, gentamicin,
      ciprofloxacin, penicillin, trimethoprim/sulfamethoxazole, erythromycin,
      tetracycline, vancomycin and cefoxitin was determined by the disc diffusion
      method. FINDINGS: Two hundred and ninety-six (36.5%) and 26 (3.2%) out of 810
      patients were S. aureus and MRSA nasal carriers, respectively. Of these, nine
      (34.6%), seven (26.9%), two (7.7%), two (7.7%), two (7.7%), one (3.8%) and one
      (3.8%) MRSA isolates were classified as type V, III, I, IVb, IVh, II and IVa,
      respectively, and seven (26.9%) MRSA isolates were non-typeable. PVL genes were
      not detected. All MRSA isolates were multi-drug resistant. CONCLUSION: A
      significant association was found between previous hospitalization, use of
      urinary and/or venous catheters and MRSA colonization. Further work on the
      epidemiology and risk factors for MRSA nasal colonization may be useful to guide
      the treatment and prevention of MRSA infections.

PMID- 25618235
TI  - Limited retention of micro-organisms using commercialized needle filters.
AB  - A study was undertaken to compare a commercialized needle filter with a 0.2-MUm
      filtered epidural set and a non-filtered standard needle. No culturable bacteria
      were detected following filtration through the 0.2-MUm filter. Bacterial
      breakthrough was observed with the filtered needle (pore size 5 MUm) and the non
      filtered needle. Filtered systems (0.2 MUm) should be employed to achieve total
      bacterial retention. This highlights that filtration systems with different pore
      sizes will have varying ability to retain bacteria. Healthcare professionals need
      to know what type/capability of filter is implied on labels used by
      manufacturers, and to assess whether the specification has the desired
      functionality to prevent bacterial translocation through needles.

PMID- 25618237
TI  - Influence of supporting polyelectrolyte layers on the coverage and stability of
      silver nanoparticle coatings.
AB  - Deposition mechanisms of citrate-stabilized silver nanoparticles 15 nm in
      diameter on cationic polyelectrolyte supporting layers were evaluated. Initially,
      the bulk and the electrokinetic properties of cationic polyelectrolytes and their
      monolayers on mica were determined using in situ streaming potential
      measurements. Analogously, the size distribution, stability and electrokinetic
      properties of silver particles were studied using transmission electron
      microscopy (TEM) and microelectrophoretic measurements. Afterward, the kinetics
      of silver particle deposition was quantitatively evaluated by a direct
      enumeration procedure exploiting the atomic force microscopy (AFM) and scanning
      electron microscopy (SEM) micrographs. Using this method the kinetics of particle
      adsorption was determined for various polyelectrolyte supporting layers as a
      function of ionic strength. These experiments were interpreted in terms of the
      random sequential adsorption (RSA) model. It was found that the highest coverage
      of 0.35 was obtained for silver monolayers deposited on poly(allylamine
      hydrochloride) (PAH)-modified mica in the case of higher ionic strength. The
      release kinetics of nanoparticles was also studied using the SEM and AFM imaging
      method. Using these experimental data the equilibrium adsorption constant and the
      binding energy of nanoparticles were calculated by exploiting the RSA approach.
      The investigations showed that the most stable silver monolayers are obtained for
      the poly-L-lysine (PLL) supporting layers where the 50% of particle is released
      after 441h, whereas in the case of PEI the release time was only 9h. These
      results are consistent with the model of discrete electrostatic interactions
      among ion pairs. Additionally, the obtained results have practical implication
      indicating that it is feasible to regulate the rate of silver nanoparticle
      release by a proper choice of the polyelectrolyte forming the supporting layer.

PMID- 25618236
TI  - Italian standardization of the Apples Cancellation Test.
AB  - Hemispatial neglect due to right parieto-temporo-frontal lesions has a negative
      impact on the success of rehabilitation, resulting in poor functional gain.
      Recent research has shown that different types of neglect can impact in a
      different way on rehabilitation outcomes. The availability of a sensitive test,
      useful for distinguishing egocentric and allocentric forms of neglect, may be
      clinically important as all current clinical instruments fail to distinguish
      between these forms of disturbance, yet they differentially predict outcome. The
      Apples Test is a new instrument useful to evaluate both egocentric and
      allocentric forms of neglect. In order to establish Italian norms for this
      diagnostic instrument the test was administered to a sample of 412 healthy people
      of both genders (201 M and 211 F), aged from 20 to 80 years enrolled from 14
      different rehabilitation centers in Italy. Based on the data, we established
      pathological performance cut-offs for the accuracy score (total omission errors),
      the asymmetry score for egocentric neglect (omission error difference), the
      asymmetry score for allocentric neglect (commission error difference) and
      execution time. The usefulness of the Apples Test for diagnostic purposes is
      illustrated by presenting three patients with different forms of neglect
      (egocentric, allocentric and mixed neglect).

PMID- 25618238
TI  - Sorption of H3BO3/B(OH)4- on calcined LDHs including different divalent metals.
AB  - LDHs with different divalent metals (Zn-LDH, Mg-LDH and Ca-LDH) have been
      synthesized and produced calcined LDHs (Zn-CLDH, Mg-CLDH and Ca-CLDH) for borate
      removal. Based on XRD, SEM, BET, (27)Al NMR, CO2-TPD, and (11)B NMR, detailed
      characterization of different CLDHs before and after reaction with the boron
      species was systematically performed. The surface area, basicity and the particle
      charge of the different CLDHs, which are related to the hydration and
      regeneration, were markably influenced by the nature of the divalent metals.
      Transformation of crystal phases and the types of boron species adsorbed by the
      different CLDHs varied as time changed. The regeneration of Ca-CLDH required the
      shortest time. However, Ca-LDH decomposed to release Ca(2+) ions, forming
      ettringite with borate. Zn-CLDH also rapidly transformed into Zn-LDH. During this
      reconstruction, B(OH)4(-) was intercalated into the interlayer of Zn-LDHs, which
      is the predominant mechanism of borate removal by Zn-CLDH. Increase in the
      initial pH caused a competition between borate and OH(-) so that the removal
      efficiency of borate by Zn-CLDH decreased. For Mg-CLDH, surface complexation and
      electrostatic attraction were included in the first stage, immobilizing boric
      acid into Mg(OH)2 and attracting borate as interlayer anionic species into the
      new forming Mg-LDHs in the second stage. 

PMID- 25618239
TI  - A facile approach to prepare porous cup-stacked carbon nanotube with high
      performance in adsorption of methylene blue.
AB  - Novel porous cup-stacked carbon nanotube (P-CSCNT) with special stacked
      morphology consisting of many truncated conical graphene layers was synthesized
      by KOH activating CSCNT from polypropylene. The morphology, microstructure,
      textural property, phase structure, surface element composition and thermal
      stability of P-CSCNT were investigated by field-emission scanning electron
      microscope, transmission electron microscope (TEM), high-resolution TEM, N2
      sorption, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy
      and thermal gravimetric analysis. A part of oblique graphitic layers were etched
      by KOH, and many holes with a diameter of several to a doze of nanometers
      connecting inner tube with outside were formed, which endowed P-CSCNT with high
      specific surface area (558.7 m(2)/g), large pore volume (1.993 cm(3)/g) and
      abundant surface functional groups. Subsequently, P-CSCNT was used for adsorption
      of methylene blue (MB) from wastewater. Langmuir model closely fitted the
      adsorption results, and the maximum adsorption capacity of P-CSCNT was as high as
      319.1mg/g. This was ascribed to multiple adsorption mechanisms including pore
      filling, hydrogen bonding, pi-pi and electrostatic interactions. Pseudo second
      order kinetic model was more valid to describe the adsorption behavior. Besides,
      P-CSCNT showed good recyclablity and reusability. These results demonstrated that
      P-CSCNT had potential application in wastewater treatment.

PMID- 25618240
TI  - Free-standing, flexible, multifunctional, and environmentally stable
      superhydrophobic composite film made of self-assembled organic micro/super
      nanostructures through solution process.
AB  - A free-standing, flexible, transparent, and fluorescent superhydrophobic
      composite film is fabricated by drop-casting a layer of organic self-assembled
      flowerlike micro/super-nanostructures on top of a hydrophobic polyimide film. The
      solution process to grow the organic super-nanostructures, fabricate the
      composite film, and lift-off the film from the mother substrate, ensures the
      process simplicity, low-cost, and scalability. The water contact angle (CA) of
      the superhydrophobic composite films reaches as high as 159.6 degrees , and the
      sliding angle (SA) is less than 2 degrees  without any further low surface energy
      treatment. The as-prepared film shows superhydrophobicity with a CA above 150
      degrees  covering the entire pH range. Moreover, the composite film exhibits good
      environmental stability against both organic solvent treatment and being exposed
      to acidic and aqueous solutions. The fluorescence from the composite film extends
      the potential application of the film into the optoelectronic field. The results
      may open up an avenue to prepare smart and intelligent superhydrophobic films for
      application. 

PMID- 25618242
TI  - Ebola crisis: the unequal impact on women and children's health.

PMID- 25618241
TI  - TGF-beta and EGF induced HLA-I downregulation is associated with epithelial
      mesenchymal transition (EMT) through upregulation of snail in prostate cancer
      cells.
AB  - Human leukocyte antigen class I antigens (HLA-I) is essential in immune response
      by presenting antigenic peptides to cytotoxic T lymphocytes. Downregulation of
      HLA-I is observed in primary and metastatic prostate cancers, which facilitates
      them escape from immune surveillance, thereby promotes prostate cancer
      progression. In addition, elevated level of growth factors like TGF-beta or EGF
      in microenvironment is related to the prostate cancer deterioration. Thus, we
      wondered whether TGF-beta or EGF was involved in the regulation of HLA-I during
      the development of prostate cancer cells. In this study, we demonstrated that TGF
      beta and EGF both downregulated the expression of HLA-I, thereby attenuated the
      cytotoxic T cell mediated lysis of prostate cancer cells. Next, we revealed that
      TGF-beta and EGF induced downregulation of HLA-I is associated with classical
      epithelial-mesenchymal transition (EMT) morphological changes and expression
      profiles. We further illustrated that overexpression of Snail is crucial for HLA
      I downregulation and its association with EMT. At last, we discussed that NF
      kappaB/p65 is the plausible target for Snail to induce HLA-I downregulation.
      Taken together, this is the first evidence to reveal that both TGF-beta and EGF
      can induce HLA-I downregulation which is then proven to be associated with EMT in
      prostate cancer cells. These discoveries provide a deeper understanding of growth
      factors induced immune escape and introduce potential therapeutic targets for
      prostate cancers. 

PMID- 25618243
TI  - Ebola interventions: listen to communities.

PMID- 25618244
TI  - Cloning, heterologous expression and biochemical characterization of plastidial
      sn-glycerol-3-phosphate acyltransferase from Helianthus annuus.
AB  - The acyl-[acyl carrier protein]:sn-1-glycerol-3-phosphate acyltransferase (GPAT;
      E.C. 2.3.1.15) catalyzes the first step of glycerolipid assembly within the
      stroma of the chloroplast. In the present study, the sunflower (Helianthus
      annuus, L.) stromal GPAT was cloned, sequenced and characterized. We identified a
      single ORF of 1344base pairs that encoded a GPAT sharing strong sequence homology
      with the plastidial GPAT from Arabidopsis thaliana (ATS1, At1g32200). Gene
      expression studies showed that the highest transcript levels occurred in green
      tissues in which chloroplasts are abundant. The corresponding mature protein was
      heterologously overexpressed in Escherichia coli for purification and biochemical
      characterization. In vitro assays using radiolabelled acyl-ACPs and glycerol-3
      phosphate as substrates revealed a strong preference for oleic versus palmitic
      acid, and weak activity towards stearic acid. The positional fatty acid
      composition of relevant chloroplast phospholipids from sunflower leaves did not
      reflect the in vitro GPAT specificity, suggesting a more complex scenario with
      mixed substrates at different concentrations, competition with other acyl-ACP
      consuming enzymatic reactions, etc. In summary, this study has confirmed the
      affinity of this enzyme which would partly explain the resistance to cold
      temperatures observed in sunflower plants. 

PMID- 25618245
TI  - Gerald M. Siegel (1932-2014) - a tribute.

PMID- 25618246
TI  - Erratum to "Experts' saliency ratings of speech-language dimensions associated
      with cluttering" [J. Fluen. Disord. 42 (2014) 35-42].

PMID- 25618249
TI  - Viral factors involved in plant pathogenesis.
AB  - Plant viruses must usurp host factors/routes for their survival. Disturbances
      derived from this extreme dependence for host resources, together with
      physiological alterations associated with defensive responses, can cause, in some
      virus-host combinations, acute or chronic plant diseases. As the coding capacity
      of these biotrophic pathogens is limited, viral-encoded proteins must essentially
      be multifunctional proteins involved in very different steps of their life cycle,
      and are usually elicitors of defensive responses. Thus, most, if not all, viral
      encoded proteins can act as pathogenicity determinants. Indeed, the viral
      proteins involved in the essential processes of their life cycle, such as
      replication, movement, encapsidation and transmission can be critical players of
      the pathogenesis process through direct or indirect interactions. This review
      updates our knowledge on how viral factors affect plant physiology and contribute
      to the development of symptomatology. 

PMID- 25618248
TI  - Study of viral pathogenesis in humanized mice.
AB  - Many of the viral pathogens that cause infectious diseases in humans have a
      highly restricted species tropism, making the study of their pathogenesis and the
      development of clinical therapies difficult. The improvement of humanized mouse
      models over the past 30 years has greatly facilitated researchers' abilities to
      study host responses to viral infections in a cost effective and ethical manner.
      From HIV to hepatotropic viruses to Middle East Respiratory Syndrome coronavirus,
      humanized mice have led to the identification of factors crucial to the viral
      life cycle, served as an outlet for testing candidate therapies, and improved our
      abilities to analyze human immune responses to infection. In tackling both new
      and old viruses as they emerge, humanized mice will continue to be an
      indispensable tool. 

PMID- 25618247
TI  - Crucial roles of canonical Runx2-dependent pathway on Wnt1-induced osteoblastic
      differentiation of human periodontal ligament fibroblasts.
AB  - Canonical Wnt signaling is thought to enhance osteogenic differentiation of human
      periodontal ligament fibroblasts (hPLFs). However, the mechanism of this
      enhancement has not yet been defined. We investigated the effects of Wnt1 on
      osteoblast differentiation of hPLFs and explored the mechanisms of the effects.
      Treating hPLFs with Wnt1 induced cytosolic accumulation and nuclear translocation
      of beta-catenin with concomitant increases in alkaline phosphatase (ALP) activity
      and calcium content in a time-dependent and dose-dependent manner. Wnt1
      stimulated differentiation of hPLFs was accompanied by augmented phosphorylation
      of glycogen synthase kinase (GSK)-3beta and expression of the bone-specific
      factors runt-related transcription factor 2 (Runx2), osterix2 (Osx2), ALP, type I
      collagen, osteopontin, and osteocalcin. Pretreatment with Dickkopf-1 inhibited
      Wnt1-stimulated differentiation of hPLFs by suppressing GSK-3beta
      phosphorylation, nuclear translocation of beta-catenin, and expression of the
      bone-specific factors. Small interfering (si) RNA-mediated knockdown of beta
      catenin, or pretreatment with FH535, markedly prevented Wnt1-stimulated
      differentiation of cells by blocking Runx2 and its downstream factors at the mRNA
      and protein levels. siRNA-mediated silencing of Runx2 also inhibited Wnt1
      stimulated mineralization of cells, accompanied by a reduction in the levels of
      Osx2 and other early and late bone-formation regulatory factors. However, Wnt1
      mediated nuclear translocation of beta-catenin and GSK-3beta phosphorylation were
      not inhibited by knockdown of Runx2 or FH535. Collectively, our findings
      suggested that Wnt1 stimulates osteogenic differentiation and mineralization of
      hPLFs, mainly by activating the canonical Wnt/beta-catenin pathway, in which
      Runx2 is a key downstream regulator. 

PMID- 25618250
TI  - Development of a more specific and accurate multiple reaction monitoring method
      based on GC-EI/MS/MS for simultaneously monitoring and determining 34 kinds of
      pesticides in Qianjinzhidai pills.
AB  - A rapid and accurate multi-residue method was developed for simultaneously
      monitoring and determining 34 kinds of pesticides by GC-EI/MS/MS, successfully
      applied in Qianjinzhidai pills. Precision, repeatability, stability, limit of
      detection (LOD), limit of quantification (LOQ), linearity range and accuracy
      tests were used to validate this method. The results, precision (RSD<2%, n=6),
      repeatability (RSD<2%, n=6) and stability (RSD<2%, n=6), LOD (lower than
      0.02mg/kg), LOQ (lower than 0.067mg/kg), linearity range (0.016-39.270MUg/mL),
      recoveries (90-110%, RSD<15%, n=6), indicated that the method was feasible. This
      paper provided an optimization method about ion transitions which can improve the
      specificity of mass spectrum monitoring and the accuracy of content
      determination. This method can be also used to monitor and determine pesticide
      residues of other traditional Chinese medicine, but it was worth noting that the
      ion transitions should been again optimized according to the sample matrix. 

PMID- 25618251
TI  - Simultaneous derivatization and solid-based disperser liquid-liquid
      microextraction for extraction and preconcentration of some antidepressants and
      an antiarrhythmic agent in urine and plasma samples followed by GC-FID.
AB  - The present work is based on a one-step method including derivatization and solid
      based disperser liquid-liquid microextraction followed by gas chromatography
      flame ionization detection (GC-FID) for the determination of four antidepressants
      (fluoxetine, fluvoxamine, tranylcypromine, and nortriptyline) and an
      antiarrhythmic agent (mexiletine) in human urine and plasma samples. In this
      method, a mixture of 1,1,2,2-tetrachloroethane (extraction solvent) and
      butylchloroformate (derivatizing reagent) is added on a sugar cube (solid
      disperser) and it is introduced into an aqueous sample containing the analytes
      and a catalyst, e.g. 3-methylpyridine (picoline). During dissolving the sugar
      cube by manual shaking, the extractant and derivatization agent are gradually
      released into the sample as very fine droplets. Then the resulted cloudy solution
      is centrifuged and the sedimented phase is analyzed by GC-FID. The influence of
      several variables on the efficiency of derivatization/microextraction procedure
      such as kind and volume of extraction solvent, type and amount of disperser,
      amount of derivatization agent, and catalyst volume are optimized. Under the
      optimum conditions the calibration curves are linear in the range of 8
      100,000MUgL(-1) (coefficient of determination >=0.994). The relative standard
      deviations are obtained in the range of 3.0-6.0% for all compounds. Moreover, the
      detection limits and enrichment factors of the target analytes are obtained in
      the ranges 1-15MUgL(-1) and 228-268, respectively, for both plasma and urine
      samples. The relative recoveries obtained for the spiked plasma and urine samples
      are between 70 and 91%. The results show that the proposed method is simple,
      reliable, low cost, and applicable to determine trace amounts of the studied
      drugs in biological samples. 

PMID- 25618252
TI  - Development and validation of an LC-MS/MS method for the determination of
      pelubiprofen and its active metabolite, trans-alcohol, in human plasma and its
      application to pharmacokinetic study.
AB  - A suitable liquid chromatography tandem mass spectrometry (LC-MS/MS) method is
      required to determine pelubiprofen and its active metabolite, trans-alcohol (M
      D), in human plasma for pharmacokinetic studies of pelubiprofen preparations.
      After one-step liquid-liquid extraction (LLE) using methyl tert-butyl ether
      (MTBE), pelubiprofen, M-D, and tolbutamide (the internal standard, IS) were
      eluted from a Capcellpak C18 ACR column using a gradient mobile phase consisting
      of 0.1% formic acid in water and acetonitrile at a flow rate 0.35mL/min. The
      achieved lower limits of quantitation (LLOQ) of pelubiprofen and M-D were both
      15ng/mL (S/N>10) and the standard calibration curves for pelubiprofen and M-D
      were linear (correlation coefficients >0.99) over the studied concentration range
      (15-2000ng/mL). Intra- and inter-day precisions were within 7.62% for all
      analytes and the deviation of assay accuracies was within +/-13.23%. The
      developed method was successfully applied to a pharmacokinetic study of
      pelubiprofen in healthy Korean male volunteers. 

PMID- 25618253
TI  - The association of visual impairment and 3-year mortality among the elderly in
      Taiwan: the Shihpai Eye Study.
AB  - BACKGROUND: The association between visual impairment and mortality has been
      controversial. Moreover, literature on the relationship was very limited in the
      Asian population. The purpose of this study was to investigate whether visual
      impairment increases the 3-year risk of mortality in a cohort of urban Chinese
      elderly individuals. METHODS: Participants in the Shihpai Eye Study, who were
      aged >=65 years, with a baseline examination conducted between July 1, 1999 and
      December 31, 2000, were recruited for the current study. The total number of
      possible participants identified was 4750. Of those, 3746 persons were eligible,
      and 2045 persons were randomly selected to be invited to participate in the
      study. Of those 2045 individuals, 1361 (66.6%) participated in both the
      questionnaire and eye examination. A follow-up of a fixed cohort was also
      conducted after 3 years. The death of any participants was confirmed through the
      household registration system. RESULTS: Of the 1361 participants included at
      baseline, 54 (3.97%) died before the 3-year follow-up. Multiple logistic
      regression analysis showed that mortality was significantly associated with a
      fall history [relative risk (RR): 2.12; 95% confidence intervals (CI): 1.08-3.98]
      and a history of diabetes (RR: 2.06; 95% CI: 1.03-3.95). Visual impairment was
      not a significant predictor of mortality after adjustment for confounders.
      CONCLUSION: After adjustments were made for age, sex, education, marital status,
      lifestyle factors, depression symptoms, fall history, and history of systemic
      diseases, visual impairment was not a significant predictor of 3-year mortality
      in elderly persons.

PMID- 25618254
TI  - Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a
      prospective observational study.
AB  - Weight loss is increasingly considered as a negative prognostic marker in
      amyotrophic lateral sclerosis (ALS). Despite the critical importance of
      nutritional issues in ALS, and the common use of percutaneous endoscopic
      gastrostomy (PEG), there is a general lack of knowledge on peri-interventional
      treatment, optimal parameters of enteral nutrition, its timing during disease
      progression and its potential disease-modifying effects in ALS patients. Here we
      report the results of a multi-center prospective study of percutaneous endoscopic
      gastrostomy (PEG) in ALS. In this observational clinical trial, 89 ALS patients
      were prospectively enrolled over a 3-year period and longitudinal data were
      collected over 18 months. PEG was a safe procedure even in patients with low
      forced vital capacity, and prophylactic single-shot antibiosis as well as slow
      increase of caloric nutrition via PEG was beneficial to avoid complications. No
      signs of refeeding syndrome were observed. High-caloric intake (>1,500 kcal/d)
      via PEG in patients that lived at least 12 months after PEG insertion was
      correlated with prolonged survival. Additional oral food intake was not
      associated with a worse prognosis. Our results suggest that peri-interventional
      PEG management should include prophylactic single-shot antibiosis, slow increase
      of caloric intake, and long-term high-caloric nutrition. Although our results
      indicate that PEG might be more beneficial when applied early, we believe that it
      can also be performed safely in patients with far advanced disease. Because of
      its explorative and observational character, most of our results have to be
      confirmed by a randomized interventional trial.

PMID- 25618255
TI  - VCP mutations are not a major cause of familial amyotrophic lateral sclerosis in
      the UK.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing loss
      of motor neurons in the spinal cord, brain stem and cerebral cortex. Mutations in
      the Valosin containing protein (VCP) gene have recently been identified in
      Familial ALS (FALS) patients, accounting for ~1% of all FALS cases. In order to
      study the frequency of VCP mutations in UK FALS patients, we have screened the
      exons known to harbour mutations together with 3' and 5' UTR sequences. No coding
      changes were identified in this UK cohort and no common polymorphisms were
      associated with FALS. However, we identified an imperfect hexanucleotide
      expansion (8 repeats), c.-221_-220insCTGCCACTGCCACTGCCG, in the 5'UTR of a FALS
      case and a 7-repeat hexanucleotide repeat in a Sporadic ALS case (SALS) that were
      not present in 219 UK controls. Subsequent screening of sequence data from 1844
      controls (1000 genomes Phase 3) revealed the presence of the 7-repeat (0.3%) and
      a single individual with an 8-repeat containing a homogeneous insert [CTGCCG]3
      but no individuals with the heterogeneous insert found in FALS
      ([CTGCCA]2[CTGCCG]). Two novel single base pair substitutions, c.-360G>C and
      c.2421+94C>T, were found in FALS cases in the 5' and 3' UTRs respectively. The
      hexanucleotide expansion and c.-360G>C were predicted to be pathogenic and were
      found in FALS cases harbouring C9orf72 expansions. The SALS case with a 7 repeat
      lacked a C9orf72 expansion. We conclude that VCP mutations are not a major cause
      of FALS in the UK population although novel rare variations in the 5' UTR of the
      VCP gene may be pathogenic. 

PMID- 25618256
TI  - Feasibility of Recruiting Peer Educators to Promote HIV Testing Using Facebook
      Among Men Who have Sex with Men in Peru.
AB  - A peer leader-based intervention using social media can be an effective means to
      encourage Peruvian gay men to test for HIV. The objective was to explore the
      feasibility of recruiting and training leaders to deliver a peer intervention via
      Facebook to promote HIV testing. Training consisted of three sessions focused on
      HIV epidemiology, consequences of stigma associated with HIV, and ways to use
      Facebook. We performed pre- and post-training evaluations to assess HIV knowledge
      and comfort using Facebook. We trained 34 peer leaders. At baseline, the majority
      of peer leaders were already qualified and knowledgeable about HIV prevention and
      use of social media. We found a significant increase in proportion of peer
      leaders who were comfortable using social media to discuss about sexual partners
      and about STIs. It is feasible to recruit peer leaders who are qualified to
      conduct a social media based HIV prevention intervention in Peru.

PMID- 25618257
TI  - Prevalence and Frequency of Heterosexual Anal Intercourse Among Young People: A
      Systematic Review and Meta-analysis.
AB  - We aim to assess if heterosexual anal intercourse (AI) is commonly practiced and
      how frequently it is practiced by young people. We searched PubMed for articles
      published 1975 to July 2014 reporting data on the proportion of young people
      (mean age <25) practicing heterosexual AI (AI prevalence) and on number of AI
      acts (AI frequency). Stratified random-effects meta-analysis and meta-regression
      were used to produce summary estimates and assess the influence of participant
      and study characteristics on AI prevalence. Eighty-three and thirteen of the 136
      included articles reported data on lifetime AI prevalence and monthly AI
      frequency, respectively. Estimates were heterogenous. Overall summary estimates
      of lifetime AI prevalence were 22 % (95 % confidence interval 20-24) among
      sexually active young people, with no statistically significant differences by
      gender, continent or age. Prevalence increased significantly with confidentiality
      of interview method and, among males and in Europe, by survey year. Prevalence
      did not significantly differ by recall period. An estimated 3-24 % of all
      reported sex acts were AI. Reported heterosexual AI is common but variable among
      young people worldwide. To fully understand its impact on STI spread, more and
      better quality data on frequency of unprotected AI, and trends over time are
      required. 

PMID- 25618258
TI  - Local expression of complement factor I in breast cancer cells correlates with
      poor survival and recurrence.
AB  - Tumor cells often evade killing by the complement system by overexpressing
      membrane-bound complement inhibitors. However, production of soluble complement
      inhibitors in cells other than hepatocytes was rarely reported. We screened
      several breast cancer cell lines for expression of soluble complement inhibitor,
      complement factor I (FI). We also analyzed local production of FI in tissue
      microarrays with tumors from 130 breast cancer patients by in situ hybridization
      and immunohistochemistry. We found expression of FI in breast adenocarcinoma cell
      line MDA-MB-468 and confirmed its functional activity. Expression of FI at mRNA
      and protein levels was also confirmed in tumor cells and tumor stroma, both in
      fibroblasts and infiltrating immune cells. Multivariate Cox regression analyses
      revealed that high expression of FI protein in tumor cells was correlated with
      significantly shorter cancer-specific survival (HR 2.8; 95 % CI 1.0-7.5; p =
      0.048) and recurrence-free survival (HR 3.4; 95 % CI 1.5-7.4; p = 0.002). High FI
      expression was positively correlated with tumor size (p < 0.001), and Nottingham
      histological grade (p = 0.015) and associated with estrogen and progesterone
      receptor status (p = 0.03 and p = 0.009, respectively). Our data show that FI is
      expressed in breast cancer and is associated with unfavorable clinical outcome.

PMID- 25618259
TI  - Radial artery applanation tonometry for continuous noninvasive arterial blood
      pressure monitoring in the cardiac intensive care unit.
AB  - BACKGROUND: Hemodynamic monitoring plays a pivotal role in the treatment of
      patients in the cardiac intensive care unit (CICU). The innovative radial artery
      applanation tonometry technology allows for continuous noninvasive arterial blood
      pressure (AP) measurement. By closing the gap between continuous invasive AP
      monitoring (arterial catheter) and intermittent noninvasive AP monitoring
      (oscillometry) this technology might improve CICU patient monitoring. We
      therefore aimed to evaluate the measurement performance of radial artery
      applanation tonometry in comparison with a radial arterial catheter in CICU
      patients. METHODS: In this prospective method comparison study, we simultaneously
      recorded AP noninvasively with radial artery applanation tonometry (T-line 200
      pro device; Tensys Medical Inc., San Diego, CA, USA) and invasively with an
      arterial catheter (criterion standard) in 30 patients treated in the CICU of a
      German university hospital. We statistically analyzed 7,304 averaged 10-beat
      epochs of measurements of mean AP, systolic AP, and diastolic AP by using Bland
      Altman analysis for repeated measurements. RESULTS: Our study revealed a mean
      difference +/- standard deviation (95% limits of agreement; percentage error)
      between radial artery applanation tonometry and the criterion standard method
      (radial arterial catheter) of +2 +/- 6 mmHg (-10 to +14 mmHg; 17%) for mean AP, 
      6 +/- 11 mmHg (-28 to +15 mmHg; 20%) for systolic AP, and +4 +/- 7 mmHg (-9 to
      +17 mmHg; 23%) for diastolic AP. CONCLUSIONS: In CICU patients, continuous
      noninvasive measurement of AP using radial artery applanation tonometry is
      feasible. The technology showed reasonable accuracy and precision in comparison
      with radial arterial catheter-derived AP values.

PMID- 25618260
TI  - Post-cataract endophthalmitis caused by multidrug-resistant Stenotrophomonas
      maltophilia: clinical features and risk factors.
AB  - BACKGROUND: To report clinical features and risk factors of post-cataract surgery
      endophthalmitis (PE) due to Stenotrophomonas maltophilia. METHODS: A
      retrospective case review from December 10, 2010 to April 7, 2011 was performed
      at the Eye & ENT Hospital, Fudan University. Data were collected for surgical
      details, disease characteristics, antibiotic sensitivity of the pathogen, and
      treatment response. Visual outcomes were examined with a minimum follow-up of 12
      months. RESULTS: Fourteen cases of S. maltophilia endophthalmitis were
      identified. The onset of infection occurred from 1-56 days postoperatively
      (median, 13.5 days). Obvious cellular reactions were found in all patients in the
      anterior chamber, along with the absence of pupil synechia. Retinal periphlebitis
      was an early sign of PE. S. maltophilia was positive in eight patients (57.1%).
      The fluids from aspiration tubes revealed the same bacteria, which were resistant
      to multiple drugs (e.g., amino glycosides, most of the beta-lactams, aztreonam,
      imipenem, and ciprofloxacin), except levofloxacin. Compared with the culture
      negative group, the infection was more rapid, more severe, and more difficult to
      control in the culture-positive group. Among 14 patients, 11 patients (78.6%)
      underwent pars plana vitrectomy (PPV) with intravitreal injection. Three patients
      had PPV twice, and three patients had intraocular lens and capsular bag removal.
      A final visual acuity of >=20/100 was achieved by 13/14 patients (92.9%).
      Complications included retinal detachment in three cases (21.4%) and recurrence
      of infection in two cases (14.8%). Statistical analysis showed that age over 90
      years and posterior capsule rupture were risk factors of infection (P=0.034 and
      P=0.034, respectively). The phacoemulsifier allowed potential contamination
      between the aspiration and irrigation tubes. CONCLUSIONS: S. maltophilia should
      be considered a pathogenic organism of PE. The infection often occurs in older
      patients with posterior capsule rupture. Intravitreal or systemic administration
      of effective antibiotics and earlier initial PPV may contribute to better
      clinical outcomes. Tubes with connections between aspiration and irrigation
      should be avoided during surgery.

PMID- 25618261
TI  - Emendation of the family Chlamydiaceae: proposal of a single genus, Chlamydia, to
      include all currently recognized species.
AB  - The family Chlamydiaceae (order Chlamydiales, phylum Chlamydiae) comprises
      important, obligate intracellular bacterial pathogens of humans and animals.
      Subdivision of the family into the two genera Chlamydia and Chlamydophila has
      been discussed controversially during the past decade. Here, we have revisited
      the current classification in the light of recent genomic data and in the context
      of the unique biological properties of these microorganisms. We conclude that
      neither generally used 16S rRNA sequence identity cut-off values nor parameters
      based on genomic similarity consistently separate the two genera. Notably, no
      easily recognizable phenotype such as host preference or tissue tropism is
      available that would support a subdivision. In addition, the genus Chlamydophila
      is currently not well accepted and not used by a majority of research groups in
      the field. Therefore, we propose the classification of all 11 currently
      recognized Chlamydiaceae species in a single genus, the genus Chlamydia. Finally,
      we provide emended descriptions of the family Chlamydiaceae, the genus Chlamydia,
      as well as the species Chlamydia abortus, Chlamydia caviae and Chlamydia felis. 

PMID- 25618262
TI  - A study of lipid- and water-soluble arsenic species in liver of Northeast Arctic
      cod (Gadus morhua) containing high levels of total arsenic.
AB  - In the present study liver samples (n=26) of Northeast Arctic cod (Gadus morhua),
      ranging in total arsenic concentrations from 2.1 to 240mg/kg liver wet weight
      (ww), were analysed for their content of total arsenic and arsenic species in the
      lipid-soluble and water-soluble fractions. The arsenic concentrations in the
      lipid fractions ranged from 1.8 to 16.4mg As/kg oil of liver, and a linear
      correlation (r(2)=0.80, p<0.001) was observed between the total arsenic
      concentrations in liver and the total arsenic concentrations in the respective
      lipid fractions of the same livers. The relative proportion of arsenolipids was
      considerably lower in liver samples with high total arsenic levels (33-240mg/kg
      ww), which contained from 3 to 7% of the total arsenic in the lipid-soluble
      fraction. In contrast liver samples with low arsenic concentrations (2.1-33mg/kg
      ww) contained up to 50% of the total arsenic as lipid-soluble species. Arsenic
      speciation analysis of the lipid-soluble fractions of the livers, using reversed
      phase high performance liquid chromatography coupled to inductively coupled
      plasma mass spectrometry (HPLC-ICP-MS), revealed the presence of several
      arsenolipids. Three major arsenic-containing hydrocarbons (C17H39AsO, C19H41AsO
      and C23H37AsO) and five arsenic-containing fatty acids (C17H35AsO3, C19H39AO3,
      C19H37AsO3, C23H37AsO3 and C24H37AsO3) were identified using HPLC coupled to
      quadrupole time-of-flight mass spectrometry (qTOF-MS). Arsenobetaine was the
      major arsenic species in the water-soluble fraction of the livers, while
      dimethylarsinate, arsenocholine and inorganic arsenic were minor constituents.
      Inorganic arsenic accounted for less than 0.1% of the total arsenic in the liver
      samples. 

PMID- 25618263
TI  - A novel c.290G>A mutation in the Factor 11 gene in a Dutch Caucasian family with
      a Factor XI deficiency.

PMID- 25618264
TI  - Life-threatening complications and outcomes in patients with malignancies and
      severe pulmonary embolism.
AB  - BACKGROUND: Data are scarce about ICU patients with malignancy and severe
      pulmonary embolism. Here, our main objective was to identify risk factors for
      life-threatening complications, organ failures, and death in ICU patients with
      severe pulmonary embolism, with special attention to the impact of malignancy. We
      also described the clinical features of PE in patients with and without
      malignancies. METHODS: Data from consecutive adults admitted to our ICU in 2002
      2011 with severe pulmonary embolism were collected retrospectively. Multivariate
      analysis was performed to look for factors associated with death, organ failures,
      or life-threatening complications (major bleeding, recurrent PE, and cardiac
      arrest). RESULTS: Of 119 included patients (42 [35%] with bilateral pulmonary
      embolism), 41 had solid malignancies, 27 hematological malignancies, and 51 no
      malignancies. The most common symptoms were syncope (40%) and hemoptysis (18%) in
      patients with solid and hematological malignancies, respectively. Life
      threatening complications occurred in 23 (19%) patients; risk factors were
      obesity (OR, 13.22; 1.93-90.70), disseminated intravascular coagulation/ischemic
      hepatitis (OR, 27.06; 5.14-142.46), fluid load >=1000 mL/24 h (OR, 6.42; 1.60
      25.76), and solid malignancy (OR, 5.45; 1.15-25.89). Inhospital mortality was
      27/119 (23%) and respiratory or circulatory failure developed in 36 (30%)
      patients. Risk factors for these adverse outcomes were older age (OR, 1.04/year;
      1.01-1.07), higher oxygen flow rate (OR, 1.28/L; 1.13-1.45); and renal failure
      (OR, 8.08; 2.50-26.11); whereas chest pain was protective (OR, 0.13; 0.04-0.48).
      CONCLUSION: In this study, solid malignancy was a risk factor for life
      threatening complications but not for death.

PMID- 25618265
TI  - Molecular characterization of p.Asp77Gly and the novel p.Ala163Val and
      p.Ala163Glu mutations causing protein C deficiency.
AB  - INTRODUCTION: Protein C (PC) is a major anticoagulant and numerous distinct
      mutations in its coding gene result in quantitative or qualitative PC deficiency
      with high thrombosis risk. Homozygous or compound heterozygous PC deficiency
      usually leads to life-threatening thrombosis in neonates. PATIENTS AND METHODS:
      The molecular consequences of 3 different missense mutations of two patients have
      been investigated. The first patient suffered from neonatal purpura fulminans and
      was a compound heterozygote for p.Asp77Gly and p.Ala163Glu mutations. The second
      patient had severe deep venous thrombosis in young adulthood and carried the
      p.Ala163Val mutation. The fate of mutant proteins expressed in HEK cells was
      monitored by ELISA, by Western blotting, by investigation of polyubiquitination
      and by functional assays. Their intracellular localization was examined by
      immunostaining and confocal laser scanning microscopy. Molecular modeling and
      dynamics simulations were also carried out. RESULTS AND CONCLUSIONS: The 163Val
      and 163Glu mutants had undetectable levels in the culture media, showed
      intracellular co-localization with the 26S proteasome and were polyubiquitinated.
      The 77Gly mutant was secreted to the media showing similar activity as the wild
      type. There was no difference among intracellular PC levels of wild type and
      mutant proteins. The 163Val and 163Glu mutations caused significant changes in
      the relative positions of the EGF2 domains suggesting misfolding with the
      consequence of secretion defect. No major structural alteration was observed in
      case of 77Gly mutant; it might influence the stability of protein complexes in
      which PC participates and may have an impact on the clearance of PC requiring
      further research.

PMID- 25618266
TI  - Establishment of a canine model of acute pulmonary embolism with definite right
      ventricular dysfunction through introduced autologous blood clots.
AB  - PURPOSE: To establish a canine model of acute pulmonary embolism (PE) with right
      ventricular (RV) dysfunction using autologous blood clots and evaluate by
      echocardiography and contrast-enhanced Computed Tomography (CT). MATERIALS AND
      METHODS: Autologous blood clots formed in vitro were introduced sequentially into
      the pulmonary arteries of eight healthy mixed-breed dogs while monitoring
      pulmonary and systemic hemodynamic function. Blood clots were injected until the
      mean pulmonary artery pressure (MPAP) reached two-three times the baseline
      pressure, which was maintained up to 1 hour. The RV function was assessed by
      echocardiography and ECG-gated dual-source contrast CT. RESULTS: All animals
      survived the imaging procedure. The post-injection pulmonary angiograms showed
      extensive PE, and MPAP increased from 16.50+/-2.45 mmHg to 43.13+/-4.91 mmHg
      (P<0.001). On echocardiography, the RV fractional area change decreased from
      42.06+/-3.36 to 27.96+/-3.54 (P<0.001), and the RV myocardial performance
      increased from 0.20+/-0.05 to 0.63+/-0.16 (P<0.001). On CT, the RV end-systolic
      volume increased from 11.11+/-1.81 ml to 24.71+/-4.60 ml (P<0.001), RV end
      diastolic volume from 20.73+/-2.83 ml to 34.63+/-5.76 ml (P<0.001), and the four
      chamber RV/left ventricular diameter ratio from 0.38+/-0.07 to 0.81+/-0.14
      (P<0.001). CONCLUSION: Acute PE with RV dysfunction was established in a large
      animal model through controlled injection of autologous blood clots, which may be
      useful for developing and evaluating new therapeutic approaches for acute PE with
      RV dysfunction.

PMID- 25618267
TI  - Liver injury may increase the risk of diazoxide toxicity: a case report.
AB  - Stress-related hyperinsulinism (HI) may lead to recalcitrant hypoglycemia for
      weeks or months following perinatal stress, often in premature newborn infants.
      Diazoxide is an effective and usually safe medication to treat this type and
      other types of neonatal HI. We report a male infant born at 35-week gestation
      with severe respiratory distress who developed prolonged hypoglycemia requiring
      high glucose infusion rates. He also had abnormal liver function tests, including
      hypoalbuminemia. Laboratory tests were consistent with HI, which responded to
      diazoxide treatment (10 mg/kg/day started at 10 days of age). The patient
      developed cardiorespiratory failure, hepatomegaly, worsening liver function
      tests, and hyperglycemia 7 weeks after the initiation of therapy. Diazoxide was
      discontinued with rapid resolution of the cardiorespiratory failure and without
      recurrence of hypoglycemia. CONCLUSION: We hypothesize that low albumin level may
      increase the toxicity of diazoxide, possibly by increasing the free diazoxide
      concentration, as this compound is typically >90% bound to plasma proteins. WHAT
      IS KNOWN: Diazoxide binds to plasma proteins >90% and excreted in urine. Dose
      adjustment is recommended in patients with impaired kidney functions. What is
      New: Literature is not available regarding diazoxide dose adjustment in patients
      with liver injury. Diazoxide toxicity is not dose-dependent.

PMID- 25618268
TI  - Effect of sleep quality on hemodynamic response to exercise and heart rate
      recovery in apparently healthy individuals.
AB  - PURPOSE: Poor sleep quality has an unfavorable impact on autonomic nervous system
      activity, especially that of the cardiovascular (CV) system. The heart rate (HR)
      and blood pressure (BP) at rest and during exercise, along with the heart rate
      recovery (HRR), were examined in poor sleepers and compared with individuals with
      good sleep quality. METHODS: A total of 113 healthy individuals were enrolled to
      the study. All participants performed treadmill stress testing. Sleep quality of
      participants was assessed by using the Pittsburgh Sleep Quality Index (PSQI)
      questionnaire: 48 subjects were categorized as 'poor sleepers' (PSQI score > 6
      points), and the rest were grouped as 'good sleepers'. RESULTS: The poor sleepers
      showed higher resting HR (p <0.001), higher diastolic BP (p=0.006), similar
      systolic BP (p=0.095), more frequent hypertensive response to exercise (p=0.046)
      and less HR increase with exercise (chronotropic incompetence) (p=0.002) compared
      with individuals who reported good sleep quality. In addition, the poor sleepers
      demonstrated reduced heart rate recovery at the 1st and 3rd minute of recovery
      (p=0.005 and 0.037, respectively) compared with good sleepers. Multivariate
      logistic regression analysis revealed that only resting diastolic BP was the
      independent predictor of HRE. The PSQI score was positively correlated with
      resting HR; while it was negatively correlated with HR response to exercise, HRR1
      and HRR index-1. CONCLUSION: This cross-sectional study emphasizes the effect of
      poor sleep quality on unfavorable cardiovascular outcome indicators of the
      treadmill stress test.

PMID- 25618269
TI  - Metabolomics in critical care medicine: a new approach to biomarker discovery.
AB  - PURPOSE: To present an overview and comparison of the main metabolomics
      techniques (1H NMR, GC-MS, and LC-MS) and their current and potential use in
      critical care medicine. SOURCE: This is a focused review, not a systematic
      review, using the PubMed database as the predominant source of references to
      compare metabolomics techniques. PRINCIPAL FINDINGS: 1H NMR, GC-MS, and LC-MS are
      complementary techniques that can be used on a variety of biofluids for
      metabolomics analysis of patients in the Intensive Care Unit (ICU). These
      techniques have been successfully used for diagnosis and prognosis in the ICU and
      other clinical settings; for example, in patients with septic shock and community
      acquired pneumonia. CONCLUSION: Metabolomics is a powerful tool that has strong
      potential to impact diagnosis and prognosis and to examine responses to treatment
      in critical care medicine through diagnostic and prognostic biomarker and
      biopattern identification.

PMID- 25618270
TI  - Evaluation of the urinary kidney injury molecule-1 levels in patients with
      diabetic nephropathy.
AB  - PURPOSE: Kidney Injury Molecule-1 is a protein that increases in urine following
      tubular damage. Kidney Injury Molecule-1 levels were correlated with the level of
      chronic kidney disease secondary to diabetic nephropathy in patients with type 2
      Diabetes Mellitus. METHODS: Clinical and laboratory findings of 142 patients with
      diabetic nephropathy and 34 control subjects were analysed. Creatinine and HbA1c
      levels in blood samples and albumin, creatinine and Kidney Injury Molecule-1
      levels in urine samples were assessed. RESULTS: Urinary Kidney Injury Molecule-1
      levels were significantly increased both in subgroups of diabetic nephropathy
      (normo-/micro-/macro-albuminuria) and in chronic kidney disease (stage 2-4)
      compared with controls. Urinary Kidney Injury Molecule-1 levels in stage 2
      chronic kidney disease patients were significantly higher than those of the
      patients with stage 3-4 chronic kidney disease. Urinary Kidney Injury Molecule-1
      levels, along with urinary albumin excretion and the duration of diabetes, were
      found to be independent risk factors associated with low glomerular filtration
      rates. CONCLUSION: Urinary Kidney Injury Molecule-1 levels seems to predict renal
      injury secondary to diabetic nephropathy in early period independent of
      albuminuria, because urinary Kidney Injury Molecule-1 was elevated despite normal
      urinary albumin excretion in the normoalbuminuric subgroup. Urinary Kidney Injury
      Molecule-1 levels, which are elevated in primarily in stage 2, shows a gradual
      decrease in patients with chronic kidney disease stages 3 and 4; thus, urinary
      Kidney Injury Molecule-1 levels may be useful in tracking the progression of
      kidney disease.

PMID- 25618271
TI  - Up-regulation of ITCH is associated with down-regulation of LATS1 during
      tumorigenesis and progression of cervical squamous cell carcinoma.
AB  - PURPOSE: The molecular basis for the normal cervical squamous epithelium advance
      to cervical intraepithelial neoplasia (CIN I, CIN II, CIN III) and ultimately to
      invasive carcinoma has not yet been defined. We explored the abnormal expression
      of ITCH (AIP4) and its degrading substrate Large Tumor Suppressor 1 (LATS1) in
      CINs and cervical cancers, which might disrupt the normal differentiation of the
      cervical epithelia and contribute to the tumorigenesis of the cervix. METHODS: A
      series of 110 samples, comprising 24 cases of normal cervical tissues, 20 cases
      of CIN I, 26 cases of CIN II/ III and 40 cases of squamous cancer of the cervix
      (SCC) were used for analysis. The expression of ITCH and LATS1 was assessed in
      the tissues by immunohistochemistry, and statistically analyzed by SPSS13.0.
      RESULTS: The increased nuclear and cytoplasmic expression levels of ITCH and the
      low membrane expression of LATS1 were strongly associated with the malignant
      transformation of the cervical epithelium and the histological progression of
      SCC. Moreover, the high nuclear and cytoplasmic expression levels of ITCH were
      significantly correlated with clinical stage (P=0.036, P=0.003, respectively) and
      tumor size (P=0.046,P=0.039, respectively); the low membrane expression of LATS1
      was significantly correlated with clinical stage (P=0.036)and tumor size
      (P=0.023). Both the nuclear and cytoplasmic expression levels of ITCH were
      inversely associated with the membrane expression of LATS1 in cervical tissues
      (P<0.001, P<0.001, respectively). CONCLUSIONS: ITCH up-regulation and LATS1 down
      regulation were closely associated with tumorigenesis and progression of SCC;
      therefore, inhibiting the expression of ITCH may serve as a novel therapeutic
      strategy for impeding the progression of precancerous neoplasm to SCC.

PMID- 25618272
TI  - A new rapamycin-abluminally coated chitosan/heparin stent system accelerates
      early re-endothelialisation and improves anti-coagulant properties in porcine
      coronary artery models.
AB  - PURPOSE: Drug-eluting stents (DES) in percutaneous coronary intervention are more
      effective in preventing in-stent restenosis compared with bare metal stents
      (BMS); however, DES may cause late stent thrombosis, which has limited its use.
      In this study, the functional properties of a newly developed DES (RAP/CS/HEP),
      in which rapamycin was abluminally-loaded onto a chitosan/heparin coating stent
      (CS/HEP), were investigated in large animal artery injury models. METHODS: The
      effectiveness of BMS, RAP (the traditional version of rapamycin DES), CS/HEP and
      RAP/CS/HEP stents in preventing coagulation and promoting re-endothelialisation
      was examined and compared in the porcine coronary artery models with
      arteriovenous shunt, high load thrombus and coronary balloon injury at day 7 and
      28, respectively, after stent implantation. The re-endothelialisation on these
      stents was further evaluated in terms of endothelial gene expression using
      quantitative RT-PCR. RESULTS: In the porcine coronary artery injury models, both
      RAP and RAP/CS/HEP stents were potent in reducing neointimal thickness, thus
      enlarging lumen area efficiently in the stented artery region compared with BMS
      and CS/HEP. RAP/CS/HEP stents facilitated re-endothelialisation and inhibited
      thrombosis more efficiently than BMS and RAP. Consistent with this, the
      expression of endothelial genes, such as CD31, CD34, eNOS and VEGF, was
      significantly elevated with RAP/CS/HEP stents compared with RAP and BMS stents.
      CONCLUSION: Abluminal coating of rapamycin onto the endothelialisation
      accelerated CS/HEP stent and may prove to be an efficient treatment for tackling
      the late stent thrombosis associated with the traditionally circumferential RAP
      stent. This new RAP/CS/HEP stent system exhibits considerably improved
      therapeutic activity.

PMID- 25618273
TI  - Hair cortisol as a biomarker of stress in the 2011 Libyan war.
AB  - PURPOSE: There is a substantial body of research that utilizes saliva cortisol
      levels to examine wartime stress; however, there is a paucity of literature that
      utilizes hair cortisol levels, which allows for long-term assessment of chronic
      stress, to investigate the stress of war. The present study aimed to evaluate
      changes in hair cortisol concentrations before, during, and after the 2011 Libyan
      war. METHODS: This study examined hair cortisol concentrations of young adult
      women who were living in Tripoli, Libya during the 2011 war. The participants
      were recruited at the campus of Tripoli University. Participants needed to have
      at least 24 cm of hair and to have resided in Tripoli before, during and after
      the 2011 Libyan war. Hair was sectioned to reflect 3 month windows of cortisol
      exposure corresponding to periods before, during and after the war. Hair cortisol
      concentrations were quantified using a modified salivary ELISA test. The women
      were also asked to complete the Perceived Stress Scale pertaining to the post-war
      period. RESULTS: Median hair cortisol concentrations in the post-war period
      (226.11 ng/g; range 122.95-519.85 ng/g) were significantly higher than both the
      pre-war (180.07 ng/g; 47.13-937.85 ng/g) and wartime (186.65 ng/g; 62.97-771.79
      ng/g) periods (P<0.05). The mean PSS score (24) was in the range of "much higher
      than the mean" for this test and the vast majority of participants were either in
      the "much higher than the mean" or "slightly higher than the mean" ranges. Hair
      cortisol determination suggests that in Tripoli, the post-war period appears to
      have been more stressful than the war itself. This is consistent with the fact
      that during the war the civilian participants were not directly involved with
      warfare, nor were they targeted by the international coalition fighting Gaddafi.
      In contrast, the post-war period was characterized by chaos and total lack of
      authority, with the participants exposed to injury, lack of food and destruction.
      CONCLUSION: This study documents the utility of hair cortisol levels to
      retrospectively assess stress before, during, and after an armed conflict.

PMID- 25618274
TI  - CSCI/RCPSC Henry Friesen lecture: controlling infectious diseases through
      vaccination.
AB  - Infectious diseases continue to cause significant morbidity and mortality in both
      animals and humans. Indeed, every year infectious diseases cost the global
      economy billions of dollars in losses and are responsible for approximately one
      third of all human deaths. These deaths occur from routine infections, hospital
      acquired infections (approximately 100,000 deaths occur annually in North America
      due to hospital-acquired infections), occasional pandemics or regional outbreaks.
      The most recent regional outbreak is Ebola in West Africa. This infection has
      caused significant challenges for the regional health care community and has had
      a global impact. The challenge in the control of infectious diseases is not only
      due to routine infections but also to the continued emergence and re-emergence of
      infectious diseases. These new threats occur on a regular basis with
      approximately thirty new emerging or re-emerging diseases recorded in the last
      thirty years. The majority of these emerging diseases are zoonotic (over 70%)
      causing even greater challenges to their control in humans and animals. 

PMID- 25618275
TI  - Joe Doupe lecture: emerging strategies for the preservation of pancreatic beta
      cell function in early type 2 diabetes.
AB  - A fundamental problem in the clinical management of type 2 diabetes is the
      inability to prevent the ongoing deterioration of pancreatic beta-cell function
      over time that underlies the chronic progressive nature of this condition.
      Importantly, beta-cell dysfunction has both reversible and irreversible
      components. Furthermore, the amelioration of reversible beta-cell dysfunction
      through the early institution of short-term insulin-based therapy has emerged as
      a strategy that can yield temporary remission of type 2 diabetes. In this
      context, we have forwarded a novel therapeutic paradigm consisting of initial
      induction therapy to improve beta-cell function early in the course of diabetes
      followed by maintenance therapy aimed at preserving this beneficial beta-cell
      effect. Ultimately, this approach may yield an optimized therapeutic strategy for
      the durable preservation of beta-cell function and consequent modification of the
      natural history of type 2 diabetes. 

PMID- 25618276
TI  - Femoro-acetabular impingement clinical research: is a composite outcome the
      answer?
AB  - Femoro-acetabular impingement (FAI) is increasingly recognized as an important
      cause of hip pain in the young adult. However, the methods of evaluating the
      efficacy of surgical intervention are often not validated and/or inconsistently
      reported. Important clinical, gait, radiographic and biomarker outcomes are
      discussed. This article (1) presents the rationale for considering a composite
      outcome for FAI patients; (2) examines a variety of important end points
      currently used to evaluate FAI surgery; (3) discusses a strategy to generate a
      composite outcome by combining these end points; and (4) highlights the
      challenges and current areas of controversy that such an approach to evaluating
      symptomatic FAI patients may present. 

PMID- 25618277
TI  - Iatrogenic medial patellar instability following lateral retinacular release of
      the knee joint.
AB  - PURPOSE: Iatrogenic medial patellar instability (IMPI) is a disabling but easily
      missed condition that is most often seen as a late complication of lateral
      retinacular release (LRR) procedures. The purposes of this study were (1) to
      summarize the available diagnostic methods and (2) to explore the contributing
      factors of IMPI following LRR procedures. METHODS: The MEDLINE, PubMed, EMBASE
      and Cochrane Library databases were searched for studies including diagnosed IMPI
      cases following LRR procedures. All patients were first divided into IMPI group
      and non-IMPI group based on the diagnostic methods of IMPI collected from
      studies. Univariate analysis was performed by comparing the two groups with
      regard to individual patient data (age at initial LRR, gender) and surgical
      details (type, releasing scope, combined surgeries and indication) of LRR
      procedures. Multivariate logistic regression was carried out to identify
      independent contributing factors for IMPI and to calculate odds ratios (ORs).
      RESULTS: Eight studies with 274 patients (300 knees) were finally included. Of
      those, 161 patients (171 knees, 57.0 %) had IMPI and 113 patients (129 knees,
      43.0 %) had no IMPI. Univariate analysis revealed a statistically significant
      difference between both groups for releasing scope (P 1 < 0.001) and indication
      of LRR procedures (P 2 < 0.001), with releasing lateral retinaculum (LR) + vastus
      lateralis (VL) tendon and absence of tight LR during the initial LRR procedures
      being more common in patients with IMPI. The independent contributing factors for
      IMPI identified in the multivariate logistic regression analysis were releasing
      LR + VL (OR1 = 16.49) and absence of tight LR (OR2 = 14.37). CONCLUSIONS: The
      IMPI was more common in patient with an over-released LRR and patient who was
      absent of tight LR during the initial LRR procedures. Aggressive surgical
      corrections and inappropriate indications of initial LRR were two contributing
      factors for the late complications of IMPI. This study suggests that the IMPI may
      occur as a major complication of LRR, especially when the VL tendon is
      extensively released or when there is no confirmative clinical evidence of a
      tight LR preoperatively. LEVEL OF EVIDENCE: IV.

PMID- 25618278
TI  - The inclination to evil and the punishment of crime - from the bible to
      behavioral genetics.
AB  - The evolving field of behavioral genetics is gradually elucidating the complex
      interplay between genes and environment. Scientific data pertaining to the
      behavioral genetics of violent behavior provides a new context for an old dilemma
      regarding criminal responsibility and punishment: if the inclination to violent
      behavior is inherent in someone's nature, how should it affect punishment for
      crime? Should it be considered as a mitigating or an aggravating factor? Given
      psychiatrists' increasing involvement in providing testimony on behavioral
      genetics in the criminal justice system, this paper first provides the necessary
      background required for understanding how this question arises and reviews the
      relevant literature. Then, we address this question from the perspective of the
      Bible and its commentators, in the belief that their insights may enrich the
      contemporary discussion of this question. 

PMID- 25618279
TI  - Voting rights for psychiatric patients: compromise of the integrity of elections,
      or empowerment and integration into the community?
AB  - BACKGROUND: Participation of the mentally-ill in elections promotes integration
      into the community. In many countries, individuals with compromised mental
      incompetence who have legal guardians are denied the right to vote. In Israel,
      mental health consumers are eligible to vote. We evaluated the capacity of
      psychiatric inpatients with and without legal guardians to understand the nature
      and effect of voting. METHODS: Fifty-six inpatients with/without legal guardians
      were recruited to the study. Participants completed the Competency AssessmentTool
      for Voting (CAT-V), Brief Psychiatric Rating Scale and the Mini-Mental State
      Exam. RESULTS: Cluster analysis determined voting capacity using CAT-V as a
      continuous variable. Subjects who scored >1.6 on the CAT-V (59%) had high
      capacity to vote. Subjects without guardians revealed significantly higher
      capacity to vote. Voting capacity positively correlated with cognitive state and
      negatively correlated with severity of illness. Among patients with legal
      guardians those who scored >1.6 on the CAT-V maintained the capacity to vote.
      CONCLUSIONS: The right to vote is an important basic right for individuals coping
      with mental disorders.However, it is important to evaluate the capacity to
      understand the voting process among individuals with mental disorders who have
      legal guardians. Thus, the integrity of the elections would be preserved by
      eliminating the risk of undue influence or manipulation of individuals who lack
      the capacity to understand the nature and meaning of voting, while preserving the
      right to vote for those with the capacity to do so, whether or not they have
      guardians.

PMID- 25618280
TI  - Examining the ethical boundaries of harm reduction: from addictions to general
      psychiatry.
AB  - Harm reduction is a general term for pragmatic interventions aimed at reducing
      problematic behaviors. Emerging from addiction treatments, it is based on the
      understanding that people will continue to behave in ways that pose a risk to
      them and their communities, and that an important goal of any treatment program
      is to minimize the harm associated with these behaviors. Despite its evidence
      based background, harm reduction is not readily applied in general psychiatry.
      This is mainly due to the complex ethical dilemmas arising within harm reduction
      practices, as well as a lack of scientific knowledge and theoretical frameworks
      essential for dealing with such ethical dilemmas. In this paper we introduce the
      fundamental theoretical and scientific base of harm reduction strategies, and
      present three clinical examples of the complex ethical dilemmas arising when
      working within a harm reduction practice. We finally present a theoretical
      framework for dealing with the ethical dilemmas and argue this may make harm
      reduction strategies more accessible in general psychiatry. 

PMID- 25618281
TI  - Using placebo medications in the clinical setting - an intellectual game or a
      possible reality?
AB  - Prior to the development of the pharmaceutical industry and the advocacy of
      evidence based medicine in the late 20th century, placebo treatments were
      commonly used by physicians. In current clinical practice, neither a physician's
      confidence in the efficacy of a specific treatment nor his personal ethical norms
      are any longer sufficient to initiate a given therapy. We will discuss whether
      placebo treatments can be ethically used in clinical practice as an alternative
      to standard therapy, and propose an innovative conceptualization of the factors
      involved in the exclusion of placebo treatments from the clinical setting.
      Patient-related ethical and interpersonal arguments and physician-related legal
      and ideological arguments concerning placebo usage are presented. We describe
      current use of placebo treatments in the healthcare system and suggest that
      placebo therapy thrives and that its therapeutic efficacy is widely acknowledged.
      There is currently "underground" use of placebo medication, open label placebo
      trials, and innovative approaches to informed consent to facilitate ethical
      prescription of placebo therapy. Finally, using the specific example of treatment
      for depression, we demonstrate how the arguments against placebo use might be
      undermined, to retrieve the legitimacy of placebo therapy. 

PMID- 25618282
TI  - Enhancing the use of institutional ethics committees in mental health care in
      Israel.
AB  - Institutional ethics committees were established and functioned in Israel prior
      to the application of the Patients Rights Act of 1996. These committees were
      voluntary and comprised of multidisciplinary teams in order to obtain numerous
      viewpoints stemming from various different fields. This intent was based on an
      understanding that the issue of ethics and the process of making ethical
      decisions inherently address moral and social considerations which are beyond the
      realm of medical practice. In contrast to the voluntary institutional ethics
      committees, the Patients Rights Act of 1996 instituted statutory ethics
      committees. These committees were mandated to investigate defined areas and, in
      contrast to the former committees that were considered to be valuable as advisory
      and enlightening entities, their decisions are binding. However, it appears that
      the utilization of these ethics committees within the domain of mental health
      facilities is limited in scope and their use varies greatly between institutions.
      The employment of these committees in mental health institutions focuses mainly
      around issues that relate to information management and mentally ill patients'
      refusal of medical treatment. Several explanations exist for this phenomenon.
      Suggestions as to how the situation may be remedied are addressed as well as the
      complementary role that these ethics committees may play in modern day clinical
      practice. 

PMID- 25618283
TI  - Patient suicide.
AB  - A series of studies reveals that patient suicide is experienced by most
      psychiatrists, particularly adult psychiatrists in the public sector.
      Psychiatrists respond to patient suicide with symptoms of grief, with an
      intensity in 25-50% of cases similar to those who have lost a parent and sought
      help, although the duration is more brief. Patient suicide usually results in
      psychiatrists becoming more defensive in their practice: extra careful to ask
      about suicidal ideation, more likely to suggest hospitalization and compulsory
      care, and seek colleagues' consultation. The frequency of patient suicide and its
      emotional and professional impact have lead to recommendations that the
      psychiatrist is supported during the early phase of shock and grief, and receives
      ongoing support for a period after the suicide. Most families of suicide patients
      would wish to have contact with the psychiatrist after the event. While distress
      and fear of litigation may influence the psychiatrist's actions, meeting with the
      family should be seen as part of care, and the psychiatrist should receive
      guidance and support in this process. 

PMID- 25618284
TI  - Real-life decision making of Serious Mental Illness patients: Opt-in and opt-out
      research participation.
AB  - BACKGROUND: Patients' decisions in relation to participation in clinical research
      depend on individual values and relevant outcomes. Presenting possible decisions
      by way of defaults (opt-in or opt-out) has been used to achieve desired outcomes.
      Our objective was to characterize patients willing to participate in clinical
      research and to assess the impact of defaults on patients with Serious Mental
      Illness (schizophrenia, schizoaffective disorder, major depression and bipolar
      disorder; SMI) during the decision process. METHODS: Patients with SMI were
      requested to accept or reject participation in a novel drug treatment study using
      either the (1) opt-in condition, wherein they were told that our center's policy
      is not to include them in drug studies; (2) the opt-out condition, wherein they
      were told that our center's policy is to include them in drug studies; and the
      (3) neutral condition that required patients to state their preference with no
      prior information. RESULTS: 311 patients with SMI completed the brief
      questionnaire within 48 hours of admission to a psychiatric ward. There were 227
      (73%) patients suffering from schizophrenia and schizoaffective disorder, 40
      (13%) suffering from bipolar disorder and 44 (14%) suffering from major
      depressive disorder. There were 156 men (50%) and 155 women in the sample, mean
      age 47.8+/-16.2 years. In the opt-in condition, 58% abstained, while 42% opted-in
      (p=0.003). In the opt-out condition, 58% participated, while 42% opted-out. In
      the neutral condition 51% indicated willingness to participate, 33% refused and
      16% were undecided. The "willing" patient was characterized by younger age,
      previous hospitalizations, affective illness and more comorbid physical
      disorders. CONCLUSION: Taken together these findings reveal the "profile" of
      patients with SMI willing to participate in clinical research and demonstrate an
      increase in participation preferences through the use of defaults.

PMID- 25618285
TI  - Ethics and the psychiatry journal editor: responsibilities and dilemmas.
AB  - An array of potential ethical stumbling blocks awaits the editors of scientific
      journals. There are issues of particular relevance to mental health journals, and
      others unique to local journals with a relatively small circulation and low
      impact factor. The blind review system, conflict of interests, redundant
      publication, fraud and plagiarism, guest and ghost authorship and ghost writing,
      advertising, language and stigma, patient consent, and "rigging" the Impact
      Factor are all issues of importance. It is critical that editors are aware and
      informed of these important issues, and have an accessible forum for evaluating
      problems as they arise. 

PMID- 25618286
TI  - Presenting problems and treatment expectations among service users accessing
      psychiatric outpatient care: are there gender differences?
AB  - BACKGROUND: Community-based studies have documented gender differences in mental
      health problems and service utilization. This mixed methods study explored gender
      differences in severity of emotional distress, referral paths, presenting
      problems and care expectations among service users upon accessing outpatient
      psychiatric care. METHODS: Consecutive service users (N=284, 64% women) who
      presented for a new or repeated episode of care in adult outpatient clinics
      completed questionnaires on a measure of emotional distress, treatment history
      and referral path. These variables were quantitatively analyzed. Also, users
      completed two open-ended questionnaires on reasons for seeking care and
      expectations from the services. These variables were qualitatively analyzed using
      thematic analyses. RESULTS: No significant gender differences emerged on any of
      the variables examined among new and repeated users. The main reasons for seeking
      care were psychiatric symptoms as well as non-specific psychopathology. The most
      frequent expectations from the services were receiving psychotherapy and specific
      tools to better manage life problems. LIMITATIONS: The sample of new male service
      users was relatively small. CONCLUSIONS: Once care is initiated, men and women
      showed similar clinical presentation and care expectations.

PMID- 25618287
TI  - Negative Emotional Eating among Obese Individuals with and without Binge Eating
      Behavior and Night Eating Syndrome.
AB  - OBJECTIVE: To assess and compare negative emotional eating among individuals with
      and without Night Eating Syndrome (NES) and Binge Eating behavior (BE). METHOD:
      The sample consisted of 76 obese participants, who were divided into four groups:
      the NES Only group; the BEOnly group; the BE and NES group; and the overweight
      control group with neither BE or NES. RESULTS: RESULTS showed significantly
      higher negative emotional eating among the BEOnly group, whereas those with NES
      Only did not report eating in direct response to negative emotions and
      situations. DISCUSSION: RESULTS suggest that individuals with BE may be using
      food as a maladaptive coping mechanism, while individuals with NES eat in the
      evening hours as a way to avoid the experience of negative emotions.

PMID- 25618288
TI  - Antenatal group therapy improves worry and depression symptoms.
AB  - INTRODUCTION: Antenatal anxiety and depression occur in approximately 20% of
      pregnant women with potentially deleterious effects to mother and child. While
      effective in reducing symptoms, some pregnant women are often reluctant to take
      psychotropic medications. We tested the effectiveness of group therapy to provide
      worry and depression symptom relief. METHODS: Women (N=38) in 15-28 weeks of
      gestation were recruited to antenatal Psychotherapy Groups using either
      interpersonal or mindfulness based therapy. We collected data at three times,
      upon intake to and at completion of the group and at four weeks postpartum.
      Descriptive, Chi-square, and GEE analyses were used to compare depression and
      worry symptoms with a matched control group of pregnant women (N=68).
      LIMITATIONS: Small sample size in both groups required a matched control group
      with no randomization. RESULTS: Attending group therapy significantly reduced
      worry and depression symptoms over pregnancy into the postpartum compared to
      women receiving no therapy. There was no difference in symptom reduction between
      different types of groups attended. DISCUSSION: Engaging pregnant women in group
      therapy can significantly improve worry and depression symptoms, with lasting
      effects.

PMID- 25618289
TI  - Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping.
AB  - Clinical response to tamoxifen varies widely among women treated with this drug
      for hormone receptor-positive breast cancer. The principal active metabolite -
      endoxifen - is generated through hepatic metabolism of tamoxifen, with key roles
      for cytochrome P450 (CYP) CYP2D6 and CYP3A. By influencing endoxifen formation,
      genetic variants of CYP2D6 may affect response to tamoxifen. After a decade of
      research, examining the effects of CYP2D6 genetic variants on tamoxifen efficacy,
      there is still no agreement on the clinical utility of CYP2D6 genotype as
      biomarker for the prediction of breast cancer outcome, because studies revealed
      conflicting results. However, tamoxifen metabolism is complex and involves
      several other drug-metabolizing enzymes. Genetic variants of other CYP enzymes,
      including CYP3A4 and CYP2C9/19, as well as co-medication interfering with the
      metabolic activity of CYP2D6 and CYP3A4 have been shown to affect endoxifen
      concentrations and may also contribute to the variability in response to
      tamoxifen. Phenotyping strategies can predict endoxifen exposure more accurately
      than CYP2D6 genotype, but do not take into account all factors influencing
      endoxifen exposure. Therapeutic drug monitoring (TDM) is likely to be the optimal
      strategy for individualization of tamoxifen treatment. According to a growing
      amount of literature, endoxifen concentration seems to be a predictor of clinical
      outcome. The relationship between endoxifen levels and breast cancer outcomes has
      to be replicated and confirmed and the value of TDM should be evaluated in
      prospective clinical trials. Caution is advised regarding the concomitant use of
      medications which could interact with tamoxifen, including inhibitors and
      inducers of CYP enzymes. 

PMID- 25618290
TI  - Treatment adherence: can fixed-dose combinations help?

PMID- 25618291
TI  - Can the metabolic syndrome be explained by a unifying concept?

PMID- 25618292
TI  - The proliferation of irrational metformin fixed-dose combinations in India.

PMID- 25618293
TI  - History written on the heart.

PMID- 25618294
TI  - Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived
      Endothelial Cells.
AB  - INTRODUCTION: The differentiated cell lineages from human embryonic stem cells
      (hESCs) and human induced pluripotent stem cells (hiPSCs) have shown their
      potential in regenerative medicine. However, the functional and transcriptional
      microRNA (miRNA) expression pattern during endothelial differentiation has yet to
      be characterized. METHODS: In this study, hESCs and hiPSCs were differentiated
      into endothelial cells (ECs). Then the endothelial-related gene profiling and
      miRNA profiling of hiPSCs, hESCs, hiPSCs derived endothelial cells (hiPSC-ECs),
      hESC derived endothelial cells (hESC-ECs) and human umbilical vein endothelial
      cells (HUVECs) were compared using RT-PCR Array. The data was analyzed using the
      data analysis system on QIAGEN's website. RESULTS: Our analysis demonstrated that
      the endothelial differentiation was triggered after EB formation and the EC
      associated genes were up-regulated swiftly in both hESC-EBs and hiPSC-EBs; hiPSC
      ECs and hESC-ECs had the similar EC-associated gene expression patterns.
      Moreover, we report here the first miRNA profiling study of hiPSC-ECs. Analyzing
      376 unique miRNAs, we have identified several interesting miRNAs, including miR
      20a, miR-20b, miR-222, miR-210, which have been previously reported to be
      involved in endothelial differentiation and show surprising expression patterns
      across our samples. We also identified novel miRNAs, such as miR-125a-5p, miR
      149, miR-296-5p, miR-100, miR-27b, miR-181a and miR-137, which were up-regulated
      in both hiPSC-ECs and hESC-ECs during endothelial differentiation. CONCLUSION:
      hiPSC-ECs and hESC-ECs exhibited a high degree of similarity with HUVECs in EC
      associated genes expression. And the miRNA profiling analysis revealed
      significant differences between hiPSCs and hESCs, but a high degree of similarity
      between hiPSC-ECs and hESC-ECs.

PMID- 25618295
TI  - Synergistic effects of hypoxia and morphogenetic factors on early chondrogenic
      commitment of human embryonic stem cells in embryoid body culture.
AB  - Derivation of articular chondrocytes from human stem cells would advance our
      current understanding of chondrogenesis, and accelerate development of new stem
      cell therapies for cartilage repair. Chondrogenic differentiation of human
      embryonic stem cells (hESCs) has been studied using supplemental and cell
      secreted morphogenetic factors. The use of bioreactors enabled insights into the
      effects of physical forces and controlled oxygen tension. In this study, we
      investigated the interactive effects of controlled variation of oxygen tension
      and chondrocyte-secreted morphogenetic factors on chondrogenic differentiation of
      hESCs in the embryoid body format (hESC-EB). Transient hypoxic culture (2 weeks
      at 5 % O2 followed by 1 week at 21 % O2) of hESC-EBs in medium conditioned with
      primary chondrocytes up-regulated the expression of SOX9 and suppressed
      pluripotent markers OCT4 and NANOG. Pellets derived from these cells showed
      significant up-regulation of chondrogenic genes (SOX9, COL2A1, ACAN) and enhanced
      production of cartilaginous matrix (collagen type II and proteoglycan) as
      compared to the pellets from hESC-EBs cultured under normoxic conditions. Gene
      expression profiles corresponded to those associated with native cartilage
      development, with early expression of N-cadherin (indicator of cell condensation)
      and late expression of aggrecan (ACAN, indicator of proteoglycan production).
      When implanted into highly vascularized subcutaneous area in immunocompromised
      mice for 4 weeks, pellets remained phenotypically stable and consisted of
      cartilaginous extracellular matrix (ECM), without evidence of dedifferentiation
      or teratoma formation. Based on these results, we propose that chondrogenesis in
      hESC can be synergistically enhanced by a control of oxygen tension and
      morphogenetic factors secreted by chondrocytes. 

PMID- 25618296
TI  - Increased expression of L-selectin (CD62L) in high-grade urothelial carcinoma: A
      potential marker for metastatic disease.
AB  - INTRODUCTION: L-Selectin (CD62L) is a vascular adhesion molecule constitutively
      expressed on leukocytes with a primary function of directing leukocyte migration
      and homing of lymphocytes to lymph nodes. In a gene expression microarray study
      comparing laser-captured microdissected high-grade muscle-invasive bladder cancer
      (MIBC) without prior treatment and low-grade bladder cancer (LGBC) human samples,
      we found CD62L to be the highest differentially expressed gene. We sought to
      examine the differential expression of CD62L in MIBCs and its clinical relevance.
      METHODS: Unfixed fresh and formalin-fixed paraffin-embedded human bladder cancer
      specimens and serum samples were obtained from the University of Connecticut
      Health Center tumor bank. Tumor cells were isolated from frozen tumor tissue
      sections by laser-captured microdissected followed by RNA isolation. Quantitative
      polymerase chain reaction was used to validate the level of CD62L transcripts.
      Immunohistochemistry and enzyme-linked immunosorbent assay were performed to
      evaluate the CD62L protein localization and expression level. Flow cytometry was
      used to identify the relative number of cells expressing CD62L in fresh tumor
      tissue. In silico studies were performed using the Oncomine database. RESULTS:
      Immunostaining showed a uniformly higher expression of CD62L in MIBC specimens
      vs. LGBCs specimens. Further, CD62L localization was seen in foci of metastatic
      tumor cells in lymph node specimens from patients with high-grade MIBC and known
      nodal involvement. Up-regulated expression of CD62L was also observed by flow
      cytometric analysis of freshly isolated tumor cells from biopsies of high-grade
      cancers vs. LGBC specimens. Circulating CD62L levels were also found to be higher
      in serum samples from patients with high-grade metastatic vs. high-grade
      nonmetastatic MIBC. In addition, in silico analysis of Oncomine Microarray
      Database showed a significant correlation between CD62L expression and tumor
      aggressiveness and clinical outcomes. CONCLUSION: These data confirm the
      expression of CD62L on urothelial carcinoma cells and suggest that CD62L may
      serve as biomarker to predict the presence of or risk for developing metastatic
      disease in patients with bladder cancer.

PMID- 25618297
TI  - Matrix metalloproteinase-9 is required for vasculogenic mimicry by clear cell
      renal carcinoma cells.
AB  - BACKGROUND: Vasculogenic mimicry (VM), a new pattern of tumor microcirculation
      system, has been proved to be important for tumor growth and progression and may
      be one of the causes of antiangiogenesis resistance. Matrix metalloproteinase-9
      (MMP9) was shown to correlate with VM formation in some other cancers. However,
      the relationship between VM formation and MMP9 in renal cell carcinoma (RCC) has
      not been determined. METHODS: The VM formation and MMP9 expressions were analyzed
      by CD34/periodic acid-Schiff dual staining and immunohistochemistry in 119 RCC
      specimens. We used a well-established 3-dimention culture model to compare VM
      formation in 786-O, 769-P, and HK-2 cell lines in vitro. MMP9 expressions on
      either messenger RNA or protein levels were compared among the cell lines by
      quantitative polymerase chain reaction or Western blot. To determine further the
      relationship between MMP9 and VM in RCC, 786-O and 769-P were treated with
      specific MMP9 inhibitor or small interfering RNA. VM formation, cell migration,
      and invasion were subsequently assessed by 3-dimention culture, wound-healing,
      and transwell assays. RESULTS: Immunohistochemistry demonstrated both VM
      formation and MMP9 overexpression were positively associated with clinical
      staging, pathological grade, and metastasis (P<0.01). VM formation was closely
      correlated with MMP9 overexpression in RCC (r = 0.602, P<0.01). Lower MMP9
      expression level was observed in normal kidney cell line HK-2, which was unable
      to form VM on Matrigel, whereas higher expression of MMP9 was found in VM-forming
      cancer cell lines 786-O and 769-P. Inhibition of MMP9 not only disrupted VM
      formation in 786-O and 769-P but also reduced cell migration and invasion.
      CONCLUSIONS: These results indicate an intimate relationship between MMP9
      overexpression and VM formation in RCC. Treatments targeting VM formation by
      inhibiting the activity of MMP9 could be beneficial in RCC therapy.

PMID- 25618298
TI  - Significance of 4E-binding protein 1 as a therapeutic target for invasive
      urothelial carcinoma of the bladder.
AB  - BACKGROUND: To evaluate the expression of multiple molecular markers involved in
      the mammalian target of rapamycin (mTOR) signaling pathway in human muscle
      invasive bladder cancer (BC) and to assess the therapeutic efficacies of mTOR
      inhibitors in human BC KoTCC-1 cells. METHODS: Expression levels of 5 markers,
      including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p
      4E-binding protein 1 (4E-BP1), were measured in radical cystectomy specimens from
      49 patients with muscle-invasive BC by immunohistochemical staining. We then
      analyzed the effects of treatment with temsirolimus or Ku-0063794, a dual
      inhibitor of mTOR complex 1 (C1) and mTOR complex 2 (C2), on changes in the
      growth and expression profiles of 5 mTOR-associated markers in KoTCC-1 cells.
      RESULTS: During the follow-up period of this study, disease recurred in 27
      patients (55.1%), and of several factors examined, the expression level of p-4E
      BP1 in addition to the pathological T stage was independently related to
      recurrence-free survival on multivariate analysis. Although the growth of KoTCC-1
      cells was inhibited by both temsirolimus and Ku-0063794 in dose-dependent
      manners, treatment with Ku-0063794 resulted in a marked decrease in the
      expression of p-4E-BP1 in KoTCC-1 cells compared with that with temsirolimus.
      Furthermore, the growth-inhibitory effect of both mTOR inhibitors was shown to be
      proportional to the expression levels of p-4E-BP1. CONCLUSIONS: The
      phosphorylation status of 4E-BP1 appeared to be correlated with the prognosis of
      patients with muscle-invasive BC following radical cystectomy as well as the
      sensitivities of BC cells to mTOR inhibitors; therefore, the inactivation of 4E
      BP1 using Ku-0063794 may be a promising novel approach for muscle-invasive BC.

PMID- 25618299
TI  - The association between cognitive deficits and depressive symptoms in at-risk
      mental state: a comparison with first-episode psychosis.
AB  - Cognitive deficits and a high prevalence of depressive symptoms have been
      reported in at-risk mental state (ARMS) for psychosis, but the relationships
      between these variables remain unclear. The Brief Assessment of Cognition in
      Schizophrenia (BACS) was administered to 50 individuals with ARMS, 50 with first
      episode psychosis (FEP), and 30 healthy controls (HC). Clinical symptoms were
      assessed by the Positive and Negative Syndrome Scale (PANSS) and the Beck
      Depression Inventory-2nd edition (BDI-II). Composite z-scores in BACS were
      compared between the three groups. Pearson correlations between composite z
      scores on the BACS and indices of clinical symptoms were compared in the ARMS and
      FEP groups. The mean composite z-scores on the BACS for the ARMS (-2.82) and FEP
      (-2.85) groups were significantly lower than the HC group (P<0.001); no
      differences between the ARMS and FEP groups emerged (P=0.995). Cognitive deficits
      and depressive symptoms were significantly correlated in the ARMS group (PANSS
      depression: r=-0.36, P=0.010; BDI-II: r=-0.34, P=0.02), while the correlation
      between cognitive deficits and negative symptoms was significant in the FEP group
      (r=-0.46, P=0.001) and approached significance in the ARMS group (r=-0.25,
      P=0.08). The correlation between cognitive deficits and depressive symptoms
      significantly differed between the ARMS and FEP groups (PANSS depression: Z=2.50,
      P=0.012; BDI-II: Z=1.96, P=0.0499). Thus, a relationship between cognitive
      deficits and depression appears to be specific to ARMS compared to FEP. 

PMID- 25618300
TI  - Effect of variation in BDNF Val(66)Met polymorphism, smoking, and nicotine
      dependence on symptom severity of depressive and anxiety disorders.
AB  - BACKGROUND: Smoking, especially nicotine dependence is associated with more
      severe symptoms of depression and anxiety disorders. However, the mechanisms
      underlying this association are unclear. We investigated the effect of brain
      derived neurotrophic factor (BDNF) Val(66)Met polymorphism on the severity of
      depressive and anxiety symptoms in never-smokers, former smokers, non-dependent,
      and nicotine-dependent smokers with a current diagnosis of depression and/or
      anxiety. METHODS: Patients with depressive or anxiety disorders and with
      available BDNF Val(66)Met polymorphism data (N=1271) were selected from
      Netherlands Study of Depression and Anxiety (NESDA). Dependent variables were
      severity of symptoms. Independent variables were smoking status and BDNF
      genotype. Age, sex, education, recent negative life events, alcohol use, body
      mass index, and physical activity were treated as covariates. RESULTS: After
      controlling for covariates, nicotine-dependent smokers had more severe depressive
      symptoms than non-dependent smokers, former and never-smokers. The latter three
      groups did not differ in severity of depression. In Val(66)Val carriers, nicotine
      dependent smokers had more severe symptoms of depression and anxiety than the
      other three groups, which were comparable in symptom severity. In Met(66)
      carriers, there were no group differences on severity of depression and anxiety.
      Nicotine dependence was the strongest predictor of severity of symptoms only in
      Val(66)Val carriers. CONCLUSIONS: In patients with a current diagnosis of
      depression or anxiety, the relationship between nicotine dependence and symptom
      severity may be moderated by BDNF Val(66)Met. These results suggest that inherent
      genetic differences may be crucial for the worse behavioral outcome of nicotine,
      and that Val(66)Val carriers may benefit most in mental health from smoking
      cessation.

PMID- 25618302
TI  - Chest pain characteristics and gender in the early diagnosis of acute myocardial
      infarction.
AB  - Acute myocardial infarction is one of the leading causes of cardiovascular
      disease mortality in both men and women. Chest pain, which is often described as
      chest pressure, tightness, or a squeezing sensation, is the most frequent symptom
      in patients presenting with acute myocardial infarction. Although the diagnosis
      of acute myocardial infarction is often based on typical changes on a surface
      electrocardiogram and on changes in cardiac biomarkers, there is a need to better
      recognize and understand the impact of sex on symptoms among patients presenting
      with acute coronary syndrome or acute myocardial infarction. We briefly review
      the pathophysiology of ischemic symptoms, discuss potential mechanisms for
      variation in ischemic symptoms by sex, and summarize recent publications that
      have addressed sex differences in ischemic symptoms. 

PMID- 25618301
TI  - Managing hypertension with ambulatory blood pressure monitoring.
AB  - There has been a dramatic shift in the manner in which blood pressure (BP) is
      measured to provide far more comprehensive clinical information than that
      provided by a single set of office BP readings. Extensive clinical and
      epidemiological research shows an important role of ambulatory BP monitoring
      (ABPM) in the management of hypertensive patients. A 24-h BP profile helps to
      determine the absence of nocturnal dipping status and evaluate BP control in
      patients on antihypertensive therapy. The ability to detect white-coat or masked
      hypertension is enhanced by ambulatory BP monitoring. In 2001, the Center for
      Medicare and Medicaid Services approved ABPM for reimbursement for the
      identification of patients with white-coat hypertension. In 2011, the National
      Institute for Health and Clinical Excellence (NICE) in the UK published
      guidelines that recommended the routine use of ABPM in all patients suspected of
      having hypertension. The European Society of Hypertension (ESH) 2013 guidelines
      also support greater use of ABPM in clinical practice. While the advantages of
      ABPM are apparent from a clinical perspective, its use should be considered in
      relation to its cost, the complexity of data evaluation, as well as patient
      inconvenience. In this review, we evaluate the clinical importance of ABPM,
      highlighting its role in the current management of hypertension. 

PMID- 25618303
TI  - Bypass grafting versus percutaneous intervention in multivessel coronary disease:
      the current state.
AB  - Whether stenting or coronary artery bypass grafting (CABG) is the best
      revascularization strategy in patients with multivessel disease has been a
      heavily debated controversy. The trials comparing the two methods were
      unfortunately underpowered for mortality. Moreover, results of clinical trials
      appeared to contradict with each other. Because CABG is unequivocally a more
      cumbersome method, stenting became commonly preferred in the absence of evidence
      for mortality difference. Meta-analysis is a powerful tool, especially when
      several high-quality randomized trials are available on the same issue. In these
      instances, meta-analyses can overcome the power limitation of the individual
      trials. Our recent meta-analysis reveals that, as compared to stenting, CABG
      leads to unequivocal reductions in mortality and myocardial infarctions in
      patients with multivessel disease. These benefits are seen regardless of whether
      patients are diabetic or not and also do not depend on whether bare-metal or drug
      eluting stents are used. 

PMID- 25618304
TI  - Statins and cognitive function: an updated review.
AB  - Ischemic heart disease remains the leading cause of death in the USA. Statins
      have substantially contributed to the decline in mortality due to heart disease.
      Historically, statins are hypothesized to be neuroprotective and beneficial in
      dementia, but recent reports have suggested an association with transient
      cognitive decline. We have critically appraised the relationship between statins
      and cognitive function in this review. Most of the data are observational and
      reported a protective effect of statins on dementia and Alzheimer's disease in
      patients with normal cognition at baseline. Few studies, including two randomized
      control trials, were unable to find a statistically significant decrease in the
      risk or improvement in patients with established dementia or decline in cognitive
      function with statin use. As more randomized control trials are required to
      definitively settle this, cardiovascular benefits of statins must be weighed
      against the risks of cognitive decline on an individual basis. 

PMID- 25618305
TI  - The role of echocardiography in hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a disease with a constellation of unique
      clinical, hemodynamic and echocardiographic features. Over the past decades,
      echocardiography has played a pivotal role in our understanding of the
      epidemiology, pathophysiology and prognosis of the condition. Recent advances in
      echocardiographic techniques have not only expanded our knowledge base but have
      also extrapolated the role of imaging from that of diagnosis, screening and non
      invasive serial assessment to identification of poor prognostic markers,
      differentiation from phenocopies of HCM and guidance of intraprocedural decision
      making in both septal ethanol ablation and surgical myectomy. This article
      summarizes the recent advances in echocardiography pertaining to HCM. 

PMID- 25618306
TI  - Echocardiographic evaluation of left ventricular diastolic function: an update.
AB  - Echocardiographic evaluation of diastolic properties and assessment of
      hemodynamic status of the right and the left ventricle have been traditionally
      applied for many years in clinical practice. Establishment of diagnosis of
      diastolic dysfunction, grading, and estimation of filling pressures noninvasively
      adds prognostic information to the clinician, which may affect treatment
      management. Novel methods, including left atrium strain, left ventricular
      diastolic strain rate, and left ventricular untwisting rate, have been imported
      in clinical practice attempting to provide a more comprehensive and more accurate
      understanding of the mechanisms and diagnosis of diastolic dysfunction. 

PMID- 25618307
TI  - Urban inclusion as wellbeing: Exploring children's accounts of confronting
      diversity on inner city streets.
AB  - The diversity of people living in a city is often most visible on inner city
      streets. These streets are also the neighbourhood environment of children who
      live in the central city. In the past, the wellbeing and sensibilities of
      children have been marginalised in planning practices in western cities but this
      is beginning to change with child-friendly and inclusive city discourses now more
      common. In this paper we report on children's experiences confronting diversity
      in inner-city Auckland. In 2012, 40 inner-city children, 9-12 years, participated
      in walking interviews in their local streets and school-based focus group
      discussions. As the children talked about their lives, moving and playing around
      neighbourhood streets, many described distress and discomfort as they confronted
      homelessness, drunkenness, and signs of the sex industry. A few older children
      also described strategies for coping with these encounters, an emerging
      acceptance of difference and pride in becoming streetwise. New Zealand (NZ) has a
      history of progressive social policy. In 2003, it became the first country in the
      world to decriminalise all forms of prostitution. Securing the health and human
      rights of sex workers were the primary drivers of the reforms. Similar concerns
      for health and rights underpin broadly inclusive local policies towards
      homelessness. To promote the health and wellbeing of inner city children their
      presence on city streets, alongside those of other marginalised groups, needs to
      be at the forefront of planning concerns. However we conclude that there are
      inherent tensions in promoting a child-friendly city in which diversity and
      inclusiveness are also valued. 

PMID- 25618308
TI  - Methane and CO2 emissions from China's hydroelectric reservoirs: a new
      quantitative synthesis.
AB  - Controversy surrounds the green credentials of hydroelectricity because of the
      potentially large emission of greenhouse gases (GHG) from associated reservoirs.
      However, limited and patchy data particularly for China is constraining the
      current global assessment of GHG releases from hydroelectric reservoirs. This
      study provides the first evaluation of the CO2 and CH4 emissions from China's
      hydroelectric reservoirs by considering the reservoir water surface and drawdown
      areas, and downstream sources (including spillways and turbines, as well as river
      downstream). The total emission of 29.6 Tg CO2/year and 0.47 Tg CH4/year from
      hydroelectric reservoirs in China, expressed as CO2 equivalents (eq), corresponds
      to 45.6 Tg CO2eq/year, which is 2-fold higher than the current GHG emission (ca.
      23 Tg CO2eq/year) from global temperate hydropower reservoirs. China's average
      emission of 70 g CO2eq/kWh from hydropower amounts to 7% of the emissions from
      coal-fired plant alternatives. China's hydroelectric reservoirs thus currently
      mitigate GHG emission when compared to the main alternative source of electricity
      with potentially far great reductions in GHG emissions and benefits possible
      through relatively minor changes to reservoir management and design. On average,
      the sum of drawdown and downstream emission including river reaches below dams
      and turbines, which is overlooked by most studies, represents the equivalent of
      42% of the CO2 and 92% of CH4 that emit from hydroelectric reservoirs in China.
      Main drivers on GHG emission rates are summarized and highlight that water depth
      and stratification control CH4 flux, and CO2 flux shows significant negative
      relationships with pH, DO, and Chl-a. Based on our finding, a substantial
      revision of the global carbon emissions from hydroelectric reservoirs is
      warranted.

PMID- 25618310
TI  - The changing faces of eosinophilic esophagitis: the impact of consensus
      guidelines at the University of South Florida.
AB  - BACKGROUND AND AIMS: Prior to the consensus guideline conference in 2007,
      eosinophilic esophagitis (EoE) was uncommon dominated by the fibrostenotic
      phenotype, but over the past decade has become a common cause of dysphagia with
      more inflammatory phenotypes diagnosed. We assessed the impact of guideline
      definitions on the characteristics of EoE phenotypes over the past 26 years at
      our institution. METHODS: We reviewed the electronic health record of 75
      consecutive patients meeting guideline definition EoE from 1/1988 to 5/2014. We
      separated groups based on 5-year intervals of diagnosis and phenotype. For
      continuous data, results were summarized as mean difference and standard
      deviation with 95 % confidence intervals. RESULTS: Five groups based on 5-year
      intervals of diagnosis were identified: group 1-1988-1993 (n = 7), group 2-1994
      1999 (n = 7), group 3-2000-2005 (n = 4), group 4-2006-2011 (n = 35), and group 5
      2012-2014 (n = 22). Prior to 2000, all patients were diagnosed with fibrostenotic
      EoE. After the initial 2007 guideline conference, inflammatory EoE has
      predominated with only one-third diagnosed with fibrostenotic EoE. Prior to 2011,
      only two were diagnosed with PPI-REE. In the last 3 years, 8 out of 22 patients
      (32 %) had PPI-REE. Overall, 8 out of 10 (80 %) PPI-REE were the inflammatory
      phenotype. When comparing pre- (n = 18) and post (n = 57)-consensus definitions,
      there was a significant difference between age of diagnosis (30.710.2 vs. 41.3 +/
      14.3; p = 0.001), age of symptom onset (18.4 +/15.2 vs. 32.4 +/- 15.5), and
      initial esophageal diameter (10.5 +/- 2.7 vs. 14.3 +/- 4.2; p < 0.0001),
      respectively. CONCLUSIONS: Fibrostenotic EoE has steadily decreased, and
      inflammatory EoE is now the most recognized form. Across our 26-year experience,
      there was a decrease in delay in diagnosis and severity of esophageal stricture.
      The pivotal change occurred around 2007 corresponding to the first EoE guideline
      emphasizing the impact and importance of early detection of disease.

PMID- 25618309
TI  - Changes of benthic bacteria and meiofauna assemblages during bio-treatments of
      anthracene-contaminated sediments from Bizerta lagoon (Tunisia).
AB  - Sediments from Bizerta lagoon were used in an experimental microcosm setup
      involving three scenarios for the bioremediation of anthracene-polluted
      sediments, namely bioaugmentation, biostimulation, and a combination of both
      bioaugmentation and biostimulation. In order to investigate the effect of the
      biotreatments on the benthic biosphere, 16S rRNA gene-based T-RFLP bacterial
      community structure and the abundance and diversity of the meiofauna were
      determined throughout the experiment period. Addition of fresh anthracene
      drastically reduced the benthic bacterial and meiofaunal abundances. The
      treatment combining biostimulation and bioaugmentation was most efficient in
      eliminating anthracene, resulting in a less toxic sedimentary environment, which
      restored meiofaunal abundance and diversity. Furthermore, canonical
      correspondence analysis showed that the biostimulation treatment promoted a
      bacterial community favorable to the development of nematodes while the treatment
      combining biostimulation and bioaugmentation resulted in a bacterial community
      that advantaged the development of the other meiofauna taxa (copepods,
      oligochaetes, polychaetes, and other) restoring thus the meiofaunal structure.
      The results highlight the importance to take into account the bacteria/meiofauna
      interactions during the implementation of bioremediation treatment.

PMID- 25618311
TI  - Systematic Review with Meta-Analysis: Alcohol Consumption and Risk of Colorectal
      Serrated Polyp.
AB  - BACKGROUND: Alcohol intake is closely related to colorectal cancer, which remains
      inconsistent with studies on the relation between alcohol consumption and risk of
      colorectal serrated polyp (SP) which was proven to have potential of developing
      into malignant serrated neoplasm. AIM: A meta-analysis investigating the
      association between alcohol intake and colorectal SP with the dose-response of
      alcohol intake was conducted. METHODS: The literature search was performed on
      PubMed to identify pertinent articles presenting results for at least three
      categories of alcohol consumption dated up to October 2014. Summarized relative
      risks (RRs) with 95 % confidence intervals (CIs) were estimated using random or
      fixed effects models based on statistical heterogeneity. RESULTS: A total of ten
      observational studies were identified in this meta-analysis. All drinkers were
      associated with 24 % increased risk of colorectal SP compared with non
      /occasional drinkers. In particular, the light alcohol intake was not related to
      an increased risk of colorectal SP (RR 1.05, 95 % CI 0.93-1.18), whereas the RRs
      were 1.19 (95 % CI 1.02-1.40) for moderate alcohol intake and 1.60 (95 % CI 1.35
      1.91) for heavy alcohol intake. The risks were consistent in further dose
      response analysis. Meanwhile, subgroup analyses demonstrated that patients in
      America had more increased risk of SP with respect to those in Europe and Asia.
      In terms of subtype of colorectal SP, alcohol consumption had a greater influence
      on SSA than HP. CONCLUSIONS: This is the first meta-analysis that demonstrated
      the relationship between moderate and heavy alcohol consumption and increasing
      risks of colorectal SP.

PMID- 25618312
TI  - Reversing Advanced Hepatic Fibrosis in NASH: Clearly Possible, but Widely at
      Hand?

PMID- 25618313
TI  - A diagnosis for L55: what is the cost of government initiatives in dementia case
      finding.

PMID- 25618315
TI  - Ageism as a Risk Factor for Chronic Disease.
AB  - Ageism is one of the most socially condoned and institutionalized forms of
      prejudice in the United States. Older adults are discriminated against in
      employment, health care, and other domains. Exposure to unfavorable stereotypes
      adversely affects the attitudes, cognitions, and behavior of older adults.
      Recurrent experiences with negative stereotypes combined with discrimination may
      make ageism a chronic stressor in the lives of older adults. The way stress
      influences physical health is gaining increasing support. The weathering
      hypothesis (Geronimus, A. T. (1992) The weathering hypothesis and the health of
      African-American women and infants: Evidence and speculations. Ethnicity and
      Disease, 2, 207-221) posits that the cumulative effects of chronic objective and
      subjective stressors and high-effort coping cause deterioration of the body,
      premature aging, and associated health problems such as chronic diseases.
      Researchers have found empirical support for the weathering hypothesis as well as
      its theorized contribution to racial and ethnic health disparities. Although
      ageism is not experienced over the entire life course, as racism typically is,
      repeated exposure to chronic stressors associated with age stereotypes and
      discrimination may increase the risk of chronic disease, mortality, and other
      adverse health outcomes. I conclude with implications for practice in the helping
      professions and recommendations for future research. Ageism warrants greater
      recognition, social condemnation, and scientific study as a possible social
      determinant of chronic disease.

PMID- 25618314
TI  - Predictive factors of myasthenic crisis after extended thymectomy for patients
      with myasthenia gravis.
AB  - OBJECTIVES: Postoperative myasthenic crisis (POMC) is one of the serious
      complications after extended thymectomy for patients with myasthenia gravis (MG).
      This study aims to clarify the risk factors of POMC occurrence. METHODS: The
      clinical data of 55 MG patients (25 male, 30 female; median age, 51 years) who
      underwent extended thymectomy at Kyoto University from 2000 to 2013 were
      retrospectively reviewed. Surgical outcomes and pre- and perioperative predictive
      factors of POMC were analysed. RESULTS: The preoperative Myasthenia Gravis
      Foundation of America stage was I, II, III and IV in 24, 22, 8 and 1 patients,
      respectively. Ten patients (18.2%) developed POMC; 6 required prolonged
      intubation over 24 h and 4 required reventilatory support. All patients were
      weaned after 5.6 (2-26) days of ventilator support, and were discharged.
      Univariate analysis revealed a correlation with a high preoperative anti
      acetylcholine receptor antibody titre (P = 0.009), history of myasthenic crisis
      (MC) (P = 0.0004) and unstable MG after preoperative medical therapy (P = 0.003).
      Multivariate logistic regression analysis showed history of MC (odds ratio,
      11.84; 95% confidential interval, 1.05-372; P = 0.045) and unstable MG (odds
      ratio, 29.45; 95% confidential interval, 2.00-1063; P = 0.013) independently
      predicted POMC. The surgical response rate was not significantly different
      between the two groups (66.7% with POMC, 85.4% without POMC; P = 0.334).
      CONCLUSIONS: POMC occurred more frequently in unstable MG before surgery or in
      patients with a history of MC. Adequate preoperative medical therapy and
      perioperative care should be provided to these patients.

PMID- 25618316
TI  - Short-term mortality of adult inpatients with community-acquired pneumonia:
      external validation of a modified CURB-65 score.
AB  - OBJECTIVE: The management of community-acquired pneumonia (CAP) continues to be a
      challenge, especially in older people. To enable better risk stratification, a
      variation of the severity scores CRB-65 and CURB-65, called CURB-age, has been
      suggested. We compared the association between risk groups as defined by the
      scores and 30-day mortality for a cohort of mainly older inpatients with CAP.
      METHODS: We retrospectively analysed data from the CAP database from the years
      2005 to 2009 of a single centre in Herne, Germany. Patient characteristics,
      criteria values within the severity scores CURB-65, CRB-65 and CURB-age, and 30
      day mortality were assessed. We compared the association between score points and
      score-defined risk groups and mortality. Sensitivity and specificity with
      corresponding 95% CIs were calculated, and receiver operating characteristic
      (ROC) curve analysis was performed. RESULTS: Data from 559 patients were analysed
      (mean age 74.1 years, 55.3% male). Mortality at day 30 was 10.9%. CURB-age
      included more patients in the low-risk category than CRB-65 (195 vs 89), and the
      patient group had a lower mortality (2.6% vs 3.4%). When compared with CURB-65,
      CURB-age included slightly fewer patients (195 vs 214) with lower mortality (2.6%
      vs 4.2%). CURB-age sorted the most patients who died within 30 days into the high
      risk CAP group (CURB-age, 32; CURB-65, 28; CRB-65, 9), which had the highest
      mortality (CURB-age, 26.4%; CURB-65, 19.4%; CRB-65, 21.4%). Advantages of CURB
      age categories were depicted through ROC curve analysis (area under the curve
      0.73 (95% CI 0.67 to 0.79) for CURB-age categories, 0.67 (95% CI 0.60 to 0.74)
      for CURB-65 categories, and 0.59 (95% CI 0.52 to 0.66) for CRB-65 categories).
      CONCLUSIONS: In comparison with CRB-65 and CURB-65, risk stratification as
      defined by CURB-age showed the closest association with 30-day mortality in our
      sample. Further prospective studies are needed to assess the potential of CURB
      age for better risk prediction, especially in older patients with CAP.

PMID- 25618317
TI  - Medication adherence and attrition to biologic treatment in rheumatoid arthritis
      patients.
AB  - PURPOSE: The objectives of this study were to assess medication adherence rate
      and attrition rate in first-time adalimumab (ADA) or etanercept (ETA) users in
      rheumatoid arthritis (RA) patients. This study also identified the risk factors
      associated with nonadherence and treatment abandonment. METHODS: This was a
      retrospective study with a 2-year follow-up. A total 2151 adult RA patients (18
      years of age and older) who initiated ADA or ETA treatment in the Kaiser
      Permanente Southern California health plan between 2002 and 2009 were identified.
      Among those on treatment in the first year, continuous treatment receipt was
      determined by having at least 1 medication refill in the second year; otherwise
      treatment was considered as abandoned. Medication adherence was measured through
      proportion of days covered (PDC) and compared between patients continuously on
      treatment and those abandoning treatment. Risk factors of nonadherence (PDC <80%)
      and treatment abandonment were estimated by a multinomial logistic regression
      model. FINDINGS: Patients who abandoned treatment had significantly lower PDC
      (37.3%) and lower average number of refills (5.1) than adherers (PDC = 88.8%;
      average number of refills = 12.4) and nonadherers (PDC = 53.3%; average refills =
      8.2). Age, African Americans (odds ratio [OR], 1.49; 95% CI, 1.03-2.17),
      corticosteroids use (OR, 0.80; 95% CI, 0.63-0.98), and history of
      physical/occupational therapy (OR = 0.66; 95% CI, 0.46-0.93) were associated with
      nonadherence, whereas having a comorbidity (OR, 1.24; 95% CI, 1.01-1.57) was
      associated with treatment abandonment. The difference in PDC between ADA and ETA
      was no longer statistically significant after excluding the treatment abandonment
      group. A higher proportion of ADA users abandoned treatment than ETA users (42.9%
      vs 32.2%). IMPLICATIONS: Taking into account treatment abandonment when measuring
      medication adherence in ADA and ETA use in RA patients can provide a fair and
      clinically meaningful view of patients' medication-taking behavior.

PMID- 25618318
TI  - An assessment of the pharmacokinetics of a sustained-release formulation of a
      tramadol/acetaminophen combination in healthy subjects.
AB  - PURPOSE: To provide consistent pain relief and improve convenient sustained
      release (SR), a fixed-dose combination tramadol/acetaminophen tablet was
      formulated. This study aimed to evaluate the pharmacokinetic profiles of an SR 75
      mg tramadol/650-mg acetaminophen formulation after a single dose compared with an
      immediate release (IR) 37.5-mg tramadol/325-mg acetaminophen formulation after 2
      doses and at steady state and to assess the effect of food on the pharmacokinetic
      SR formulation profile after a single dose. METHODS: Two clinical trials were
      conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study
      to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen
      combination tablet) formulation profiles after a single dose and IR (one 37.5-mg
      tramadol/325-mg acetaminophen combination tablet q6h for 2 doses) formulation
      profiles after 2 doses and the effect of food intake on healthy male subjects and
      (2) an open, randomized, 2-period, 2-treatment multiple dose crossover study to
      evaluate the steady-state pharmacokinetic SR and IR formulation profiles. Safety
      assessments were performed. FINDINGS: Forty-three subjects completed each study
      protocol. The SR combination tramadol/acetaminophen formulation was clinically
      and statistically equivalent to the IR combination formulation in the fasting
      state. When tramadol and acetaminophen tablets were administered with food, the
      time to peak plasma concentrations and the tramadol/acetaminophen absorption were
      unaffected. There was no serious adverse event reported. IMPLICATIONS: The SR
      combination tramadol/acetaminophen tablet exhibited similar exposure and
      absorption rates compared with those of the IR formulation of tramadol, O
      desmethyltramadol, and acetaminophen. The SR formulation may be more convenient
      for patients and has the potential to enhance compliance and pain control.
      ClinicalTrials.gov identifier: NCT01880125.

PMID- 25618320
TI  - Maintenance of certification: Good intentions gone awry.

PMID- 25618319
TI  - Factors affecting viability of Bifidobacterium bifidum during spray drying.
AB  - BACKGROUND: There is substantial clinical data supporting the role of
      Bifidobacterium bifidum in human health particularly in benefiting the immune
      system and suppressing intestinal infections. Compared to the traditional
      lyophilization, spray-drying is an economical process for preparing large
      quantities of viable microorganisms. The technique offers high production rates
      and low operating costs but is not usually used for drying of substances prone to
      high temperature. The aim of this study was to establish the optimized
      environmental factors in spray drying of cultured bifidobacteria to obtain a
      viable and stable powder. METHODS: The experiments were designed to test
      variables such as inlet air temperature, air pressure and also maltodextrin
      content. The combined effect of these variables on survival rateand moisture
      content of bacterial powder was studied using a central composite design (CCD).
      Sub-lethal heat-adaptation of a B. bifidum strain which was previously adapted to
      acid-bile-NaCl led to much more resistance to high outlet temperature during
      spray drying. The resistant B. bifidum was supplemented with cost friendly
      permeate, sucrose, yeast extract and different amount of maltodextrin before it
      was fed into a Buchi B-191 mini spray-dryer. RESULTS: Second-order polynomials
      were established to identify the relationship between the responses andthe three
      variables. Results of verification experiments and predicted values from fitted
      correlations were in close agreement at 95% confidence interval. The optimal
      values of the variables for maximum survival and minimum moisture content of B.
      bifidum powder were as follows: inlet air temperature of 111.15 degrees C, air
      pressure of 4.5 bar and maltodextrin concentration of 6%. Under optimum
      conditions, the maximum survival of 28.38% was achieved while moisture was
      maintained at 4.05%. CONCLUSION: Viable and cost effective spray drying of
      Bifidobacterium bifidum could be achieved by cultivating heat and acid adapted
      strain into the culture media containing nutritional protective agents.

PMID- 25618321
TI  - My approach to patients with acute pericarditis.

PMID- 25618322
TI  - Dying with cardiovascular disease, not of it.

PMID- 25618323
TI  - Olfactory specialization in Drosophila suzukii supports an ecological shift in
      host preference from rotten to fresh fruit.
AB  - It has been demonstrated that Drosophila suzukii is capable of attacking ripening
      fruit, making it a unique species within a fly family named for their attraction
      towards the fermentation products associated with rotten fruits, vinegar, and
      yeast. It also has been hypothesized that D. suzukii is more attracted to the
      volatiles associated with the earlier ripening stages of fruit development, and
      in turn, that D. suzukii is less attracted to fermented food resources,
      especially when compared with D. melanogaster. Here, we demonstrate that D.
      suzukii and its close relative D. biarmipes are in fact more sensitive to
      volatiles associated with the fruit-ripening process; however, in choice-assays,
      both spotted-wing species are more attracted to fermented fruit than to earlier
      stages of fruit development, which is similar to the behavioral preferences of D.
      melanogaster, and thus, fruit developmental stage alone does not explain the
      ecological niche observed for D. suzukii. In contrast, we show that both D.
      suzukii and D. biarmipes are more attracted to leaf odors than D. melanogaster in
      behavioral trials. For D. suzukii, this differential behavioral preference
      towards leaves appears to be linked to beta-cyclocitral, a volatile isoprenoid
      that we show is most likely a novel ligand for the "ab3A" neuron. In addition,
      this compound is not detected by either of the other two tested fly species. 

PMID- 25618324
TI  - A new lavandulol-related monoterpene in the sex pheromone of the grey pineapple
      mealybug, Dysmicoccus neobrevipes.
AB  - The grey pineapple mealybug, Dysmicoccus neobrevipes, is a serious pest that
      attacks a variety of crops in tropical regions. Recently, it was recorded on an
      island in southwestern Japan, suggesting that its distribution is expanding. As a
      measure against this expansion, a monitoring tool is urgently needed. In this
      study we determined the structure of the sex pheromone of D. neobrevipes in order
      to develop an efficient lure for monitoring traps. Volatiles collected from
      virgin adult females were fractionated by high performance liquid chromatography
      (HPLC) and gas chromatography, and fractions were tested for attractiveness to
      males in a laboratory bioassay. A single compound was isolated which was as
      attractive to males as the crude collections, and this was proposed to be the
      main, if not the only, component of the female-produced sex pheromone. The
      structure of this was determined to be (E)-2-isopropyl-5-methylhexa-3,5-dienyl
      acetate by gas chromatography/mass spectrometry and nuclear magnetic resonance
      analyses. This compound was synthesized through four steps, and the synthetic
      chemical was as attractive as the natural product in a greenhouse bioassay. The
      enantiomers of the synthetic acetate were obtained by enantioselective HPLC
      fractionation of the corresponding alcohols, and the natural pheromone was shown
      to be the (+)-isomer. The carbon skeleton of this novel compound is related to
      lavandulol, a monoterpene with an unusual non-head-to-tail connection of isoprene
      units that is often found in mealybug pheromones. 

PMID- 25618325
TI  - Neural substrate of cognitive theory of mind impairment in amyotrophic lateral
      sclerosis.
AB  - We now know that amyotrophic lateral sclerosis (ALS) is not restricted to the
      motor system. Indeed, a large proportion of patients with ALS exhibit cognitive
      impairment, especially executive dysfunction or language impairment. Although
      researchers have recently turned their attention to theory of mind (ToM) in ALS,
      only five studies have been performed so far, and they reported somewhat
      contradictory results. Moreover, the neural basis of the potential ToM deficit in
      ALS remains largely unknown. The present study was therefore designed to clarify
      whether a cognitive ToM deficit is indeed associated with ALS, specify the
      putative link between cognitive ToM deficits and executive dysfunction in ALS,
      and identify the dysfunctional brain regions responsible for any social cognition
      deficits. We investigated cognitive ToM and executive functions in a group of 23
      patients with ALS and matched healthy controls, using an original false-belief
      task and a specially designed battery of executive tasks. We also performed an
      (18)F-fluorodeoxyglucose positron emission tomography examination. Results
      confirmed the presence of cognitive ToM deficits in patients compared with
      controls, and revealed significant correlations between ToM and executive
      functions, although the cognitive ToM deficit persisted when a composite
      executive function score was entered as a covariate. Using statistical parametric
      mapping, we calculated positive correlations between tracer uptake and false
      belief scores on a voxel-by-voxel basis in the patient sample. Results showed
      that the cognitive ToM deficit correlated with the dorsomedial and dorsolateral
      prefrontal cortices, as well as the supplementary motor area. Our findings
      provide compelling clinical and imaging evidence for the presence of a genuine
      cognitive ToM deficit in patients with ALS. 

PMID- 25618326
TI  - Fast, but not slow, familiarity is preserved in patients with amnestic mild
      cognitive impairment.
AB  - Recognition memory--affected early in the course of Alzheimer Disease (AD)--is
      supposed to rely on two processes: recollection (i.e., retrieval of details from
      the encoding episode) and familiarity (i.e., acontextual sense of prior
      exposure). Recollection has repeatedly been shown to be impaired in patients with
      amnestic Mild Cognitive Impairment (aMCI)--known to be at high risk for AD.
      However, studies that evaluated familiarity in these patients have reported
      conflicting results. Here, we assessed familiarity in single-domain aMCI patients
      (n = 19) and healthy matched controls (n = 22). All participants underwent a
      classic yes/no recognition memory paradigm with confidence judgements, allowing
      an estimation of familiarity and recollection similar to the approach used in
      previous studies. In addition, they underwent a novel speeded recognition memory
      task, the Speed and Accuracy Boosting procedure, based on the idea that
      familiarity is fast and hence that fast answers rely on familiarity. On the
      classic yes/no task, aMCI patients were found to have impaired performance,
      reaction times, recollection and familiarity. However, performance and reaction
      times of aMCI patients did not differ from that of controls in the speeded task.
      This is noteworthy since this task was comparatively difficult for control
      subjects. This dissociation within familiarity suggests that a very basic
      component of declarative memory, probably at the interface between implicit and
      explicit memory, may be preserved, or possibly released, in patients with aMCI.
      It is suggested that early subprocesses (e.g., fluency based familiarity) could
      be preserved in aMCI patients, while delayed ones (e.g., conceptual fluency, post
      retrieval monitoring, confidence assessment, or even access to awareness) may be
      impaired. These findings may provide support for recent suggestions that
      familiarity may result from the combination of a set of subprocesses, each with
      its specific temporal signature.

PMID- 25618327
TI  - Selective reorienting response of the left hemisphere to invalid visual targets
      in the right side of space: relevance for the spatial neglect syndrome.

PMID- 25618328
TI  - Ciliary ectosomes: transmissions from the cell's antenna.
AB  - The cilium is the site of function for a variety of membrane receptors, enzymes
      and signal transduction modules crucial for a spectrum of cellular processes.
      Through targeted transport and selective gating mechanisms, the cell localizes
      specific proteins to the cilium that equip it for the role of sensory antenna.
      This capacity of the cilium to serve as a specialized compartment where specific
      proteins can be readily concentrated for sensory reception also makes it an ideal
      organelle to employ for the regulated emission of specific biological material
      and information. In this review we present and discuss an emerging body of
      evidence centered on ciliary ectosomes - bioactive vesicles released from the
      surface of the cilium. 

PMID- 25618330
TI  - A comparative study on the expression profile of MCTs and HSPs in Ghungroo and
      Large White Yorkshire breeds of pigs during different seasons.
AB  - Thermal stress has a significant adverse effect on commercial swine production
      but it is not easy to measure. Animals may adapt to stress conditions by an
      alteration in the expression of stress-related genes such as heat shock proteins
      (HSPs) and monocarboxylate transporters (MCTs). The present study presents a
      comparative analysis of seasonally varied effects on the expression profiles of
      HSPs (27, 70, and 90) and MCTs (1, 2, and 4) transcripts in thigh muscle and
      colon tissue of Ghungroo and Large White Yorkshire (LWY) breeds of pig. By real
      time polymerase chain reaction, the mRNA expression of HSP27 and HSP90 genes was
      found to be higher in both thigh muscle and colon tissue in Ghungroo compared to
      Large White Yorkshire pigs during the summer. However, the relative expression of
      HSP70 was significantly higher (P < 0.01) in Ghungroo compared to Large White
      Yorkshire pigs during both seasons in both thigh muscle and colon tissue. The
      expression of HSP90 was higher in Ghungroo when compared to LWY though the
      variation was non-significant (P > 0.05) in the colon during different seasons.
      However, in Ghungroo, the mRNA expression of MCT1 was found to be significantly
      (P < 0.05) higher in thigh muscle and colon regions during the summer compared to
      LWY, whereas MCT2 was expressed more in the colon in LWY compared to Ghungroo
      during the summer. The relative expression of mRNA of MCT4 was found to be
      significantly (P < 0.05) higher in thigh region in both summer and winter in
      Ghungroo compared with LWY. Thus, the study demonstrated that both HSPs and MCTs
      gene expression during thermal stress suggests the possible involvement of these
      genes in reducing the deleterious effect of thermal stress, thus maintaining
      cellular integrity and homeostasis in pigs. These genes could be used as suitable
      markers for the assessment of stress in pigs. 

PMID- 25618332
TI  - Identification of therapeutic small-molecule leads in cultured cells using
      multiplexed pathway reporter readouts.
AB  - The rapid expansion of molecular screening libraries in size and complexity in
      the last decade has outpaced the discovery rate of cost-effective strategies to
      single out reagents with sought-after cellular activities. In addition to
      representing high-priority therapeutic targets, intensely studied cell signaling
      systems encapsulate robust reference points for mapping novel chemical activities
      given our deep understanding of the molecular mechanisms that support their
      activity. In this chapter, we describe strategies for using transcriptional
      reporters of several well-interrogated signal transduction pathways coupled with
      high-throughput biochemical assays to fingerprint novel compounds for drug target
      identification agendas. 

PMID- 25618329
TI  - IQGAPs choreograph cellular signaling from the membrane to the nucleus.
AB  - Since its discovery in 1994, recognized cellular functions for the scaffold
      protein IQGAP1 have expanded immensely. Over 100 unique IQGAP1-interacting
      proteins have been identified, implicating IQGAP1 as a critical integrator of
      cellular signaling pathways. Initial research established functions for IQGAP1 in
      cell-cell adhesion, cell migration, and cell signaling. Recent studies have
      revealed additional IQGAP1 binding partners, expanding the biological roles of
      IQGAP1. These include crosstalk between signaling cascades, regulation of nuclear
      function, and Wnt pathway potentiation. Investigation of the IQGAP2 and IQGAP3
      homologs demonstrates unique functions, some of which differ from those of
      IQGAP1. Summarized here are recent observations that enhance our understanding of
      IQGAP proteins in the integration of diverse signaling pathways. 

PMID- 25618331
TI  - Genetic manipulation of cardiac Hsp72 levels does not alter substrate metabolism
      but reveals insights into high-fat feeding-induced cardiac insulin resistance.
AB  - Heat shock protein 72 (Hsp72) protects cells against a variety of stressors, and
      multiple studies have suggested that Hsp72 plays a cardioprotective role. As
      skeletal muscle Hsp72 overexpression can protect against high-fat diet (HFD)
      induced insulin resistance, alterations in substrate metabolism may be a
      mechanism by which Hsp72 is cardioprotective. We investigated the impact of
      transgenically overexpressing (Hsp72 Tg) or deleting Hsp72 (Hsp72 KO) on various
      aspects of cardiac metabolism. Mice were fed a normal chow (NC) or HFD for 12
      weeks from 8 weeks of age to examine the impact of diet-induced obesity on
      metabolic parameters in the heart. The HFD resulted in an increase in cardiac
      fatty acid oxidation and a decrease in cardiac glucose oxidation and insulin
      stimulated cardiac glucose clearance; however, there was no difference in Hsp72
      Tg or Hsp72 KO mice in these rates compared with their respective wild-type
      control mice. Although HFD-induced cardiac insulin resistance was not rescued in
      the Hsp72 Tg mice, it was preserved in the skeletal muscle, suggesting tissue
      specific effects of Hsp72 overexpression on substrate metabolism. Comparison of
      two different strains of mice (BALB/c vs. C57BL/6J) also identified strain
      specific differences in regard to HFD-induced cardiac lipid accumulation and
      insulin resistance. These strain differences suggest that cardiac lipid
      accumulation can be dissociated from cardiac insulin resistance. Our study finds
      that genetic manipulation of Hsp72 does not lead to alterations in metabolic
      processes in cardiac tissue under resting conditions, but identifies mouse strain
      specific differences in cardiac lipid accumulation and insulin-stimulated glucose
      clearance. 

PMID- 25618333
TI  - Applying the logic of genetic interaction to discover small molecules that
      functionally interact with human disease alleles.
AB  - Despite rapid advances in the genetics of complex human diseases, understanding
      the significance of human disease alleles remains a critical roadblock to
      clinical translation. Here, we present a chemical biology approach that uses
      perturbation with small molecules of known mechanism to reveal mechanistic and
      therapeutic consequences of human disease alleles. To maximize human
      applicability, we perform chemical screening on multiple cell lines isolated from
      individual patients, allowing the effects of disease alleles to be studied in
      their native genetic context. Chemical screen analysis combines the logic of
      traditional genetic interaction screens with analytic methods from high
      dimensionality gene expression analyses. We rank compounds according to their
      ability to discriminate between cell lines that are mutant versus wild type at a
      disease gene (i.e., the compounds induce phenotypes that differ the most across
      the two classes). A technique called compound set enrichment analysis (CSEA),
      modeled after a widely used method to identify pathways from gene expression
      data, identifies sets of functionally or structurally related compounds that are
      statistically enriched among the most discriminating compounds. This
      chemical:genetic interaction approach was applied to patient-derived cells in a
      monogenic form of diabetes and identified several classes of compounds (including
      FDA-approved drugs) that show functional interactions with the causative disease
      gene, and also modulate insulin secretion, a critical disease phenotype. In
      summary, perturbation of patient-derived cells with small molecules of known
      mechanism, together with compound-set-based pathway analysis, can identify small
      molecules and pathways that functionally interact with disease alleles, and that
      can modulate disease networks for therapeutic effect. 

PMID- 25618334
TI  - Construction and application of a photo-cross-linked chemical array.
AB  - Chemical array technology is a powerful tool for high-throughput screening of
      small-molecule ligand-protein interactions. A chemical array is a collection of
      small-molecule compounds spotted and immobilized on a glass slide surface,
      providing a multiplex platform to identify small-molecule compounds binding to a
      protein of interest in high-throughput screening. Several research groups have
      developed a variety of methods for the immobilization of small molecules onto a
      solid matrix. We have developed a unique photo-cross-linked chemical array for
      immobilizing small molecules in a functional-group-independent manner. In this
      chapter, we describe in detail a protocol for the construction of a photo-cross
      linked chemical array and its application for ligand screening by using a tag
      fused protein. 

PMID- 25618335
TI  - High content screening for modulators of cardiac differentiation in human
      pluripotent stem cells.
AB  - Chemical genomics has the unique potential to expose novel mechanisms of complex
      cellular biology through screening of small molecules in in vitro assays of a
      biological phenotype of interest, followed by target identification. In the case
      of disease-specific assays, the cellular proteins identified might constitute
      novel drug targets, and the small molecules themselves might be developed as drug
      leads. In cardiovascular biology, a chemical genomics approach to study the
      formation of cardiomyocyte, vascular endothelial, and smooth muscle lineages
      might contribute to therapeutic regeneration. Here, we describe methods used to
      develop high content screening assays implementing multipotent cardiovascular
      progenitors derived from human pluripotent stem cells and have identified novel
      compounds that direct cardiac differentiation. 

PMID- 25618337
TI  - Fission yeast-based high-throughput screens for PKA pathway inhibitors and
      activators.
AB  - Features of the fission yeast Schizosaccharomyces pombe cAMP/PKA pathway make S.
      pombe particularly amenable for heterologous expression of cAMP pathway proteins
      such as GalphaS subunits and their cognate adenylyl cyclases, PKA catalytic and
      regulatory subunits, and cyclic nucleotide phosphodiesterases. We have
      constructed two PKA-repressed reporters for use in high-throughput screens to
      detect compounds that elevate or reduce PKA activity, thus facilitating the
      discovery of both inhibitors and activators of these target proteins. Here, we
      describe steps to construct screening strains and to optimize and conduct these
      screens. 

PMID- 25618338
TI  - A method for high-throughput analysis of chronological aging in
      Schizosaccharomyces pombe.
AB  - The measurement of chronological life span (CLS) in Schizosaccharomyces pombe is
      traditionally performed by plating back aliquots of aging liquid cultures on
      solid medium and counting the number of colony-forming units (CFU). However, this
      method is labor and cost intensive and therefore not amenable to high-throughput
      screening. Here, we describe a simple method for CLS measurement using aging
      minicultures in microtiter plates and batch plate-back for the determination of
      culture viability. This assay can be used to screen a large number of strains,
      conditions, or compounds in parallel for effects on aging. 

PMID- 25618336
TI  - Small-molecule high-throughput screening utilizing Xenopus egg extract.
AB  - Screens for small-molecule modulators of biological pathways typically utilize
      cultured cell lines, purified proteins, or, recently, model organisms (e.g.,
      zebrafish, Drosophila, C. elegans). Herein, we describe a method for using
      Xenopus laevis egg extract, a biologically active and highly tractable cell-free
      system that recapitulates a legion of complex chemical reactions found in intact
      cells. Specifically, we focus on the use of a luciferase-based fusion system to
      identify small-molecule modulators that affect protein turnover. 

PMID- 25618339
TI  - Protocols for the routine screening of drug sensitivity in the human parasite
      Trichomonas vaginalis.
AB  - Trichomonas vaginalis is a sexually transmitted protozoan parasite of humans.
      Treatment of trichomoniasis is almost completely dependent on the old drug
      metronidazole and is hampered by resistance. New drug development, like routine
      screening for drug resistance, has however been hampered by the lack of reliable
      screening protocols with sufficient throughput. Here we report on two separate in
      vitro protocols that use fluorescent dyes and allow for standardized drug
      sensitivity testing on the required scale. 

PMID- 25618340
TI  - Chemical genetic screens using Arabidopsis thaliana seedlings grown on solid
      medium.
AB  - Genetic screening has been a powerful tool in identifying new genes in a pathway
      of interest (forward genetics) or attributing function to a particular gene via
      mutagenesis (reverse genetics). Small molecule-based chemical genetics is
      increasingly adapted in Arabidopsis research as a tool for similar purposes,
      i.e., to identify genes involved in certain biological processes and to dissect
      the biological roles of a gene. Chemical genetic screens have been successful in
      circumventing genetic redundancy to assign biological roles to a gene family as
      well as novel functions for well-known genes. Here, we describe how to screen
      Arabidopsis seedlings grown on solid medium with chemical compounds. 

PMID- 25618341
TI  - Small-molecule screening using Drosophila models of human neurological disorders.
AB  - Within the last decade, Drosophila has emerged as a premiere model system for the
      study of human neurodegenerative diseases, due to the realization that flies and
      humans share many structurally and functionally related gene families.
      Development of such disease models in the fly allows genetic approaches to be
      applied to address specific hypotheses concerning disease progression and to test
      candidate modifier genes. More recently these fly models have also been used for
      drug discovery. Here, we describe how to utilize the existing fruit fly models of
      human neurological disorders to identify small-molecule leads that could
      potentially be further developed for therapeutic use. 

PMID- 25618342
TI  - High-throughput small-molecule screening in Caenorhabditis elegans.
AB  - Chemical compounds, which modulate enzymatic activities or those which induce
      specific phenotypes of interest, are valuable probes to study biological
      phenomena, as they allow modulation of enzymatic activities and temporal control
      of protein action. Here, we describe the methodology to conduct large-scale
      screens for chemical compounds that induce a desired phenotype in the roundworm
      Caenorhabditis elegans (C. elegans) using 96- or 384-well microtiter plates. 

PMID- 25618343
TI  - Whole-organism screening for modulators of fasting metabolism using transgenic
      zebrafish.
AB  - Organismal energy homeostasis is maintained by complex interorgan communications
      making the discovery of novel drugs against metabolic diseases challenging using
      traditional high-throughput approaches in vitro. Here, we describe a method that
      rapidly identifies small molecules with an impact on organismal energy balance in
      vivo. Specifically, we developed a whole-organism screen for modulators of
      fasting metabolism using transgenic bioluminescence-reporter zebrafish for the
      gluconeogenic gene phosphoenolpyruvate-carboxykinase 1 (pck1). 

PMID- 25618344
TI  - High content screening for modulators of cardiovascular or global developmental
      pathways in zebrafish.
AB  - Major developmental pathways play critical roles in wide array of human
      pathologies. Chemical genomic screening allows for the discovery of novel tools
      not only to target known pathway interactors but also to discover new, chemically
      tractable targets for known pathways. The zebrafish has emerged as a useful model
      for developmental biology and has been well characterized. The zebrafish
      represents a hardy conglomerate of totipotent cells that are massively and
      simultaneously assessing all significant pathways in parallel in an endogenous
      context. This represents a gold standard for biological assays, chemically
      targeting select pathways without causing pleiotropic effects. Here, we describe
      methods used to develop high content screening assays implementing transgenic
      zebrafish to assess phenotypic changes that have identified several classes of
      novel compounds that effect developmental pathways. 

PMID- 25618345
TI  - Extraction methods of natural products from Traditional Chinese medicines.
AB  - In recent years, many research activities have focused on Natural Products (NPs)
      derived from Traditional Chinese medicines (TCMs), thus making a renaissance in
      the drug discovery process of TCMs. Maximizing the diversity of extracts from
      those plants is the key for the chemical biology process. Methods for the
      preparation and pretreatment of plant extracts are very important for further
      purification and discovery of active compounds present in minor quantities. In
      this chapter, two methods of extraction, including one of the most broadly
      applicable method (solvent extraction) and one newly developed technique
      (supercritical fluid extraction), have been described in detail. 

PMID- 25618346
TI  - Bioassay-guided identification of bioactive molecules from traditional Chinese
      medicines.
AB  - Traditional Chinese medicines (TCMs) serve as a major source of a variety of drug
      lead compounds. In the process of natural products development, bioassay-guided
      isolation is a rapid and validated method for isolation of compounds with
      bioactivities. This chapter describes bioassay-guided separation and purification
      of compounds from the crude extracts of TCMs. Two approaches including size
      exclusion chromatography (SEC) and high performance liquid chromatography (HPLC)
      are described in detail. 

PMID- 25618347
TI  - NMR screening in fragment-based drug design: a practical guide.
AB  - Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS)
      to find hits and elaboration of these hits to lead compounds. Typical fragment
      hits have lower molecular weight (<300-350 Da) and lower initial potency but
      higher ligand efficiency when compared to those from high-throughput screening.
      NMR spectroscopy has been widely used for FBDD since it identifies and localizes
      the binding site of weakly interacting hits on the target protein. Here we
      describe ligand-based NMR methods for hit identification from fragment libraries
      and for functional cross-validation of primary hits. 

PMID- 25618348
TI  - Practical strategies for small-molecule probe development in chemical biology.
AB  - The effective identification, selection, and implementation of small molecules
      for the interrogation of biological systems require an intricate understanding of
      the chemical principles underlying their cellular activities. While much has been
      published regarding the use of screening techniques in forward chemical genetics
      platforms and on small-molecule target identification, less emphasis has been
      placed on detailed strategies for evaluating, selecting, and optimizing screening
      hits. This chapter provides practical tools for identifying and developing
      promising screening hit compounds into effective tools for biological discovery. 

PMID- 25618349
TI  - Principal component analysis as a tool for library design: a case study
      investigating natural products, brand-name drugs, natural product-like libraries,
      and drug-like libraries.
AB  - Principal component analysis (PCA) is a useful tool in the design and planning of
      chemical libraries. PCA can be used to reveal differences in structural and
      physicochemical parameters between various classes of compounds by displaying
      them in a convenient graphical format. Herein, we demonstrate the use of PCA to
      gain insight into structural features that differentiate natural products,
      synthetic drugs, natural product-like libraries, and drug-like libraries, and
      show how the results can be used to guide library design. 

PMID- 25618350
TI  - Small-molecule library screening by docking with PyRx.
AB  - Virtual molecular screening is used to dock small-molecule libraries to a
      macromolecule in order to find lead compounds with desired biological function.
      This in silico method is well known for its application in computer-aided drug
      design. This chapter describes how to perform small-molecule virtual screening by
      docking with PyRx, which is open-source software with an intuitive user interface
      that runs on all major operating systems (Linux, Windows, and Mac OS). Specific
      steps for using PyRx, as well as considerations for data preparation, docking,
      and data analysis, are also described. 

PMID- 25618351
TI  - Fluorous photoaffinity labeling to probe protein-small molecule interactions.
AB  - Identifying cellular targets of bioactive small molecules is essential for their
      applications as chemical probes or drug candidates. Of equal importance is to
      determine their "off-target" interactions, which usually account for unwanted
      properties including toxicity. Among strategies to profile small molecule
      interacting proteins, photoaffinity labeling has been widely used because of its
      distinct advantages such as sensitivity. When combined with mass spectrometry,
      this approach can provide additional structural and mechanistic information, such
      as drug-target stoichiometry and exact interacting amino acid residues. We have
      described a novel fluorous photoaffinity labeling approach, in which a fluorous
      tag is incorporated into the photoaffinity labeling reagent to enable the
      enrichment of the labeled species from complex mixtures for analysis. This new
      feature likely makes the fluorous photoaffinity labeling approach suitable to
      identify transient interactions, and low-abundant, low-affinity interacting
      proteins in a cellular environment. 

PMID- 25618352
TI  - Identification of the targets of biologically active small molecules using
      quantitative proteomics.
AB  - Currently, cell-based screenings yield a multitude of small molecule modulators
      of diverse biological processes. The most demanding step in the course of
      elucidation of the mode of action of biologically active compounds is the
      identification of the target proteins. Although there is no generic approach
      available, affinity-based chemical proteomics is the most widely applied
      methodology. Particularly, quantitative chemical proteomics has proven very
      powerful in the identification of the putative targets of small molecules. Here
      we describe the procedure for identification of target proteins for small
      molecules employing affinity chromatography and the stable isotope labeling in
      cell culture (SILAC) for quantitative proteomics. 

PMID- 25618353
TI  - Drug affinity responsive target stability (DARTS) for small-molecule target
      identification.
AB  - Drug affinity responsive target stability (DARTS) is a relatively quick and
      straightforward approach to identify potential protein targets for small
      molecules. It relies on the protection against proteolysis conferred on the
      target protein by interaction with a small molecule. The greatest advantage of
      this method is being able to use the native small molecule without having to
      immobilize or modify it (e.g., by incorporation of biotin, fluorescent,
      radioisotope, or photoaffinity labels). Here we describe in detail the protocol
      for performing unbiased DARTS with complex protein lysates to identify binding
      targets of small molecules and for using DARTS-Western blotting to test, screen,
      or validate potential small-molecule targets. Although the ideas have mainly been
      developed from studying molecules in areas of biology that are currently of
      interest to us and our collaborators, the general principles should be applicable
      to the analysis of all molecules in nature. 

PMID- 25618354
TI  - Chemical genomic profiling via barcode sequencing to predict compound mode of
      action.
AB  - Chemical genomics is an unbiased, whole-cell approach to characterizing novel
      compounds to determine mode of action and cellular target. Our version of this
      technique is built upon barcoded deletion mutants of Saccharomyces cerevisiae and
      has been adapted to a high-throughput methodology using next-generation
      sequencing. Here we describe the steps to generate a chemical genomic profile
      from a compound of interest, and how to use this information to predict molecular
      mechanism and targets of bioactive compounds. 

PMID- 25618355
TI  - Image-based prediction of drug target in yeast.
AB  - Discovering the intracellular target of drugs is a fundamental challenge in
      biomedical research. We developed an image-based technique with which we were
      able to identify intracellular target of the compounds in the yeast Saccharomyces
      cerevisiae. Here, we describe the rationale of the technique, staining of yeast
      cells, image acquisition, data processing, and statistical analysis required for
      prediction of drug targets. 

PMID- 25618356
TI  - Chromatographic adsorption of serum albumin and antibody proteins in cryogels
      with benzyl-quaternary amine ligands.
AB  - The preparation and characterization of mixed-mode adsorbents for a typical
      separation purpose are of great importance in bioseparation areas. In this work,
      we prepared a new monolithic cryogel with a combination of ion-exchange and
      hydrophobic functions by employing benzyl-quaternary amine groups. The
      fundamental cryogel properties, protein equilibrium adsorption isotherm and
      chromatographic adsorption in the cryogel were measured experimentally. The
      results showed that, by using bovine serum album as the model protein, the dual
      functional cryogel has protein binding capability even in salt solution and the
      buffer with pH close or below the protein isoelectric point due to both the
      electrostatic and hydrophobic interactions. A capillary-based adsorption model
      was developed, which provided satisfied insights of the microstructure, axial
      dispersion, mass transfer as well as protein adsorption characteristics within
      the cryogel bed. The chromatographic isolation of bioactive proteins from rabbit
      blood serum was carried out by the cryogel. Immunoglobulin G antibody with a
      purity of 98.2% and albumin with a purity of 96.8% were obtained, indicating that
      the cryogel could be an interesting and promising adsorbent in bioseparation
      areas. 

PMID- 25618357
TI  - The role of protein and peptide separation before mass spectrometry analysis in
      clinical proteomics.
AB  - The purpose of clinical proteomics is to characterise protein profiles of a
      plethora of diseases with the aim of finding specific biomarkers. These are
      particularly valuable for early diagnosis, and represent key molecules suitable
      to elucidate pathogenic mechanisms. Samples deriving from patients (i.e. blood,
      urine, cerebrospinal fluid, biopsies) are the sources for clinical proteomics.
      Due to the complexity of the extracted samples their direct analysis is
      unachievable. Any analytical clinical proteomics study should start with the
      choice of the optimal combination of strategies with respect to both sample
      preparations and MS approaches. Protein or peptide fractionation (off-line or on
      line) is essential to reduce complexity of biological samples and to achieve the
      most complete and reproducible analysis. The aim of this review is to introduce
      the readers to a functional range of strategies to help scientists in their
      proteomics set up. In particular, the separation approaches of proteins or
      peptides (both gel-based and gel-free) are reviewed with special attention paid
      to their advantages and limitations, and to the different liquid chromatography
      techniques used to peptide fractionation after protein enzymatic digestion and
      before their detection. Finally, the role of mass spectrometry (MS) for protein
      identification and quantification is discussed including emerging MS data
      acquisition strategies. 

PMID- 25618358
TI  - Quantification of furanic derivatives in fortified wines by a highly sensitive
      and ultrafast analytical strategy based on digitally controlled microextraction
      by packed sorbent combined with ultrahigh pressure liquid chromatography.
AB  - An improved, reliable and powerful analytical strategy based on digitally
      controlled microextraction by packed sorbent (MEPS) combined with ultrahigh
      pressure liquid chromatography (UHPLC) was validated for the simultaneous
      identification and quantification of major furanic derivatives, namely 5
      hydroxymethyl-2-furaldehyde (5HMF), 5-methyl-2-furaldehyde (5MF), 2-furaldehyde
      (2F) and 2-furyl methyl ketone (2FMK), in fortified wines. To enhance the
      extraction efficiency of the target furanic derivates, several influencing
      extraction parameters, such as number of loading cycles, nature of elution
      solvent and elution volume, were evaluated and optimized. In addition the ability
      of different MEPS sorbent materials, namely C2, C8, C18, SIL, M1, R-AX, R-CX and
      PGC, were also tested. The optimal analytical conditions involved loading 3*200
      MUL of wine samples through a C8 sorbent in a MEPS syringe placed in the semi
      automatic eVolH syringe followed by elution using 200 MUL MeOH:H2O (95:5, v/v).
      The furanic derivates separation was achieved using a CORTECS UPLC((r)) C18
      analytical column in an ultrafast chromatographic run (within 4 min). The method
      performance was assessed for dry/medium dry (D/MD) and sweet/medium sweet (S/MS)
      model wines in terms of selectivity, linearity, limit of detection (LOD), limit
      of quantitation (LOQ), accuracy, precision and matrix effect, using model wine
      matrix-matched calibration. Good linearity was obtained with a regression
      coefficient (r(2)) higher than 0.992. A good precision was attained (RSD<5%) and
      low LODs were achieved for D/MD (4.5-129.3 ng L(-1)) and S/MS (6.9-285.2 ng L(
      1)) model wines. The quantification limits (LOQ) for D/MD model wines ranged from
      14.9 to 431.0 ng L(-1), whereas for S/MS model wines range from 23.1 to 950.5 ng
      L(-1). The method also afforded satisfactory results in terms of accuracy,
      ranging from 74 to 97% for D/MD wines and between 84 and 99% for S/MS wines. The
      MEPS(C8)/UHPLC-PDA analytical strategy was successfully applied to analyze
      furanic derivates in 26 fortified Madeira wines from different types (D/MD, S/MS)
      and ages. The obtained results revealed the analytical strategy as a suitable
      tool which combines sensitivity, effectiveness, reduced analysis time and simple
      analytical procedure. Principal component analysis (PCA) suggested that fortified
      wines can be organized based on their age on PC1, which are mainly characterized
      by 5HMF.

PMID- 25618359
TI  - A comprehensive molecular dynamics approach to protein retention modeling in ion
      exchange chromatography.
AB  - In downstream processing, the underlying adsorption mechanism of biomolecules to
      adsorbent material are still subject of extensive research. One approach to more
      mechanistic understanding is simulating this adsorption process and hereby the
      possibility to identify the parameters with strongest impact. So far this method
      was applied with all-atom molecular dynamics simulations of two model proteins on
      one cation exchanger. In this work we developed a molecular dynamics tool to
      simulate protein-adsorber interaction for various proteins on an anion exchanger
      and ran gradient elution experiments to relate the simulation results to
      experimental data. We were able to show that simulation results yield similar
      results as experimental data regarding retention behavior as well as binding
      orientation. We could identify arginines in case of cation exchangers and
      aspartic acids in case of anion exchangers as major contributors to binding. 

PMID- 25618360
TI  - Editorial to "The many faces of packed-column supercritical fluid chromatography-
      a critical review" by Eric Lesellier and Caroline West.

PMID- 25618361
TI  - Nanoscale-supported heteropoly acid as a new fiber coating for solid-phase
      microextraction coupled with gas chromatography-mass spectrometry.
AB  - In the present study, 12-tungstophosphoric (PW) acid as heteropoly acid,
      supported on silica-coated gamma-Fe2O3 nanoparticles (NPs), was used as a new
      fiber coating for solid-phase microextraction (SPME). The gamma-Fe2O3@SiO2-PW
      nanocomposite with high surface area was synthesized and characterized by SEM and
      FT-IR. The prepared nanocomposite was immobilized on a stainless steel wire for
      fabrication of the SPME fiber. The fiber was evaluated for the extraction of some
      phenolic compounds (PCs) from water sample in combination with gas chromatography
      mass spectrometry (GC-MS). A one-at-a-time optimization strategy was applied for
      optimizing the important extraction parameters such as extraction temperature,
      extraction time, ionic strength, stirring rate, pH, and desorption temperature
      and time. In optimum conditions, the repeatability for one fiber (n=3), expressed
      as relative standard deviation (R.S.D. %), was between 4.8% and 9.6% for the test
      compounds. The detection limits for the studied compounds were between 0.004 and
      0.05 pg mL(-1). The developed method offers the advantage of being simple to use,
      with shorter analysis time, lower cost of equipment, thermal stability of fiber
      and high relative recovery in comparison to conventional methods of analysis.

PMID- 25618362
TI  - Estimation of the phase ratio in reversed-phase high-performance liquid
      chromatography.
AB  - Phase ratio Phi for an HPLC column is a common parameter being defined as the
      ratio between the volume of the stationary phase V(st) and the void volume of the
      column V0. Although apparently simple, the evaluation of phase ratio presents
      difficulties because there is no sharp boundary between the mobile phase and the
      stationary phase, and different mobile phases lead to different "effective" phase
      ratios. A considerable number of studies have been dedicated to the evaluation of
      V(st) and V0 with the goal of obtaining the value for Phi. However, the parameter
      is seldom reported for common commercially available columns and key information
      for its calculation (e.g. the weight of column packing) is not typically reported
      by the vendors. Present study describes a novel procedure for the evaluation of
      phase ratio for a chromatographic column when used with a given mobile phase. The
      procedure allows the calculation of Phi only from the measurements of retention
      factors k' for two hydrocarbons i and j, for which the octanol/water partition
      coefficients log K(ow) are known. A theoretical support for this procedure based
      on solvophobic theory of interactions in solution is presented, and several
      experimental results reported in the literature are used to demonstrate the
      validity of the procedure.

PMID- 25618363
TI  - Review of hexabromocyclododecane (HBCD) with a focus on legislation and recent
      publications concerning toxicokinetics and -dynamics.
AB  - In this paper, we review recent publications regarding the toxicokinetics and 
      dynamics of the flame retardant Hexabromocyclododecane (HBCD). HBCD has recently
      been listed as a persistent organic pollutant, which therefore influenced the
      legislation concerning its manufacturing and formulation. However, under specific
      circumstances it may still be used until 2024. Early toxicity studies have only
      focussed on HBCD itself, which is a mixture of different isomers with different
      physical and toxicological characteristics. Here we take a more differentiated
      look at the three diastereomers alpha-, beta- and gamma-HBCD. We also address the
      different enantiomers to give an overview of the toxicity of HBCD to identify
      present gaps in our knowledge about this chemical, especially with respect to its
      possible formulation until 2024. 

PMID- 25618364
TI  - Long-chain perfluoroalkyl carboxylic acids in Pacific cods from coastal areas in
      northern Japan: a major source of human dietary exposure.
AB  - This study investigates perfluoroalkyl carboxylic acids (PFCAs) contamination of
      edible fish muscle from Japanese coastal waters. The concentrations of PFCAs with
      8-14 carbon atoms (C8-C14) in Pacific cods in Hokkaido, Japan were 51 (median:
      pg/g-wet weight) for C8, 93 for C9, 99 for C10, 746 for C11, 416 for C12, 404 for
      C13, and 93 for C14. The levels of C9-C14 PFCAs in fish were strongly correlated
      to each other, but not to C8 and the other chlorinated persistent organic
      pollutants, indicating that C9-C14 PFCAs have a different emission source and/or
      bioaccumulation mechanism. The relative ratios between estimated PFCAs intake
      through fish consumption and the reported total dietary exposure of PFCAs were
      less than 1 for C8 to C9, but were more than 1 for C10 to C14. This result
      strongly suggests that fish consumption is a significant source of human dietary
      exposure to C10-C14 PFCAs. 

PMID- 25618365
TI  - Ground-level O3 pollution and its impacts on food crops in China: a review.
AB  - Ground-level ozone (O3) pollution has become one of the top environmental issues
      in China, especially in those economically vibrant and densely populated regions.
      In this paper, we reviewed studies on the O3 concentration observation and O3
      effects on food crops throughout China. Data from 118 O3 monitoring sites
      reported in the literature show that the variability of O3 concentration is a
      function of geographic location. The impacts of O3 on food crops (wheat and rice)
      were studied at five sites, equipped with Open Top Chamber or O3-FACE (free-air
      O3 concentration enrichment) system. Based on exposure concentration and stomatal
      O3 flux-response relationships obtained from the O3-FACE experimental results in
      China, we found that throughout China current and future O3 levels induce wheat
      yield loss by 6.4-14.9% and 14.8-23.0% respectively. Some policies to reduce
      ozone pollution and impacts are suggested. 

PMID- 25618366
TI  - Effects of silver nanoparticles to soil invertebrates: oxidative stress
      biomarkers in Eisenia fetida.
AB  - Silver nanoparticles (Ag-NPs) are among the most produced NPs worldwide having
      several applications in consumer products. Ag-NPs are known to cause oxidative
      stress in several organisms and cell lines, however comparatively less
      information is available regarding their effects on soil living invertebrates.
      The purpose of this study was to investigate if Ag-NPs cause oxidative stress on
      soil invertebrates. The model soil species Eisenia fetida was used. Our results
      showed that total glutathione (TG) is the first mechanism triggered by Ag-NPs,
      followed by glutathione peroxidase (GPx) and glutathione reductase (GR), however
      oxidative damage was observed for higher doses and exposure time (increased lipid
      peroxidation, LPO). AgNO3 exposure caused impairment in GPx and glutathione-S
      transferase (GST), probably as result of the higher bioavailability of Ag in the
      salt-form. The current results indicate that effects are partly caused by Ag ions
      released from Ag-NPs, but specific particle effects cannot be excluded. 

PMID- 25618367
TI  - A distributed network of low-cost continuous reading sensors to measure
      spatiotemporal variations of PM2.5 in Xi'an, China.
AB  - Fine particulate matter (PM2.5) is a growing public health concern especially in
      industrializing countries but existing monitoring networks are unable to properly
      characterize human exposures due to low resolution spatiotemporal data. Low-cost
      portable monitors can supplement existing networks in both developed and
      industrializing regions to increase density of sites and data. This study tests
      the performance of a low-cost sensor in high concentration urban environments.
      Seven Portable University of Washington Particle (PUWP) monitors were calibrated
      with optical and gravimetric PM2.5 reference monitors in Xi'an, China in December
      2013. Pairwise correlations between the raw PUWP and the reference monitors were
      high (R(2) = 0.86-0.89). PUWP monitors were also simultaneously deployed at eight
      sites across Xi'an alongside gravimetric PM2.5 monitors (R(2) = 0.53). The PUWP
      monitors were able to identify the High-technology Zone site as a potential PM2.5
      hotspot with sustained high concentrations compared to the city average
      throughout the day.

PMID- 25618368
TI  - Characterizing the parent and alkyl polycyclic aromatic hydrocarbons in the Pearl
      River Estuary, Daya Bay and northern South China Sea: influence of riverine
      input.
AB  - Distributions of 31 parent polycyclic aromatic hydrocarbons (PAHs) and 29 alkyl
      PAHs in surface sediments of the Pearl River Estuary (PRE), Daya Bay (DYB) and
      northern South China Sea (SCS) were examined to study the influence of riverine
      input. It was found that the contributions of riverine input to sediment PAHs in
      PRE was much higher than other areas. However, higher proportion of alkyl PAHs
      and low molecular weight PAHs in DYB and the northern SCS was observed,
      indicating their different sources. Nevertheless, the sediment PAHs in PRE were
      heterogeneous and affected by the hydrodynamic conditions. The high molecular
      weight PAHs were dominant in PRE and enriched in the depositional area of
      suspended particular matter (SPM). Moreover, the concentration of PAHs in SPM was
      similar to those in surface sediments and dominated in water columns. Therefore,
      SPM played a very important role in transportation and distribution of PAHs in
      PRE. 

PMID- 25618369
TI  - [Two decades of bridging activities between pharmacology, epidemiology and public
      health in Spain].
AB  - Unsurprisingly, disciplines such as epidemiology, public health and pharmacology
      have points of confluence. Consequently, in Spain, both professionals and
      organizations from these disciplines have collaborated on many different
      activities altogether. This article compiles two decades of shared initiatives
      among these fields, coordinated by the Esteve Foundation. We discuss 20
      collaborations, including face-to-face activities and joint publications. These
      activities involved numerous institutions and over 1,000 professionals. Among
      other activities, we would like to stress the training activities in scientific
      writing and editing. In particular, we highlight the 32 editions of a training
      workshop on how to write a scientific article, which has been running since 2004
      to the present day. We conclude that collaborations between different
      institutions and professionals have acted and will continue to act as a bridge
      between disciplines and to contribute to scientific progress from a
      multidisciplinary perspective. 

PMID- 25618370
TI  - Temporal bone fractures: sequelae and their impact on quality of life.
AB  - PURPOSE: To present a prospective temporal bone fracture database, and study
      facial and cochleovestibular sequelae and their impact on quality of life.
      MATERIALS AND METHODS: Prospective study of consecutive cases of 39 patients with
      45 temporal bone fractures over 11-month period in a university tertiary referral
      center. Based on epidemiological data, clinical and imaging findings, treatment
      modalities and outcome of patients with follow-up of one year, the present study
      focused on facial and cochleovestibular sequelae and their impact on quality of
      life after one-year period. RESULTS: After 12 months, 44% of patients present
      with balance problems, 56% with hypoacusis, 56% with tinnitus, and 15% with
      facial paralysis. In 75%-80% of patients, the cochleovestibular sequelae are
      described as disabling. Post-trauma quality of life was significantly impaired
      compared with pre-trauma quality of life, even after 12 months. Long-term
      cochleovestibular sequelae were significantly associated with poor long-term
      quality of life. CONCLUSIONS: The study demonstrates the need to focus on
      prevention of temporal bone fractures, notably by promoting the use of helmets
      and improvements in helmet design. The rapid diagnosis of temporal bone fracture
      is crucial as it enables effective initial management aimed at avoiding sequelae.
      The frequency of cochleovestibular sequelae after temporal bone fracture and
      their impact on quality of life demonstrate the importance of, and need for,
      ongoing follow-up by a local medical team who can diagnose and manage these long
      term sequelae.

PMID- 25618372
TI  - An integrated microfluidic system for measurement of glycated hemoglobin levels
      by using an aptamer-antibody assay on magnetic beads.
AB  - Blood glycated hemoglobin (HbA1c), reflecting the average blood glucose level in
      the proceeding 2-3 months, is recommended for screening/diagnosing and patient
      management of diabetes. However, accurate measurement of the HbA1c level at the
      point of care is hampered by costly, large-scale instruments (such as high
      performance liquid chromatography) or reagent instability of classical
      immunologic methods, which involve antibody-based immunoturbidimetry. In this
      work, an integrated microfluidic system using aptamer-based testing to measure
      HbA1c in blood samples is therefore presented. This measuring system used nucleic
      acid aptamers that exhibited high sensitivity and high specificity for hemoglobin
      and HbA1c to perform a stable and robust testing. The compact microfluidic system
      consumed less samples and reagents and significantly shortened the detection
      time. Combining the advantages of microfluidics and aptamers, this integrated
      microsystem presents a promising tool for accurate and point-of-case HbA1c
      detection. To demonstrate its clinical utility, whole blood samples with
      clinically-relevant concentrations of HbA1c and Hb were automatically measured on
      the integrated microfluidic system. Experimental data showed that the developed
      aptamer-based microfluidic system is capable of detecting HbA1c and Hb with a
      good linear response. The entire process was completed within 25 min. The aptamer
      antibody on-chip sandwich immunoassay may be further refined to allow diabetes
      screening and diagnosis at lower cost and earlier phase to minimize the risk of
      diabetic complications.

PMID- 25618371
TI  - Recurrent amplification of MYC and TNFRSF11B in 8q24 is associated with poor
      survival in patients with gastric cancer.
AB  - BACKGROUND: Gastric cancer (GC) is an aggressive malignancy whose mechanisms of
      development and progression are poorly understood. The identification of
      prognosis-related genomic loci and genes may suffer from the relatively small
      case numbers and a lack of systematic validation in previous studies. METHODS:
      Array-based comparative genomic hybridization (aCGH) coupled with patient
      clinical information was applied to identify prognosis-related loci and genes
      with high-frequency recurrent gains in 129 GC patients. The candidate loci and
      genes were then validated using an independent cohort of 384 patients through
      branched DNA signal amplification analysis (QuantiGene assays). RESULTS: In the
      129 patients, a copy number gain of three chromosome regions-namely, 8q22
      (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13
      (including SRC, MMP9, and CSE1L)--conferred poor survival for patients. In
      addition, the correlation between the branched DNA signal amplification analysis
      results and the aCGH results was analyzed in 73 of these 129 patients, and MYC,
      TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further
      validation using an independent cohort (n = 384) verified that only MYC and
      TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC
      and TNFRSF11B had poorer survival than those with no gains, particularly those
      with noncardia GC. Gains in both of these genes were also a significant
      independent prognostic indicator. CONCLUSIONS: Our results revealed that copy
      number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in
      GC, particularly noncardia GC.

PMID- 25618373
TI  - Paper-based electrochemiluminescence origami device for protein detection using
      assembled cascade DNA-carbon dots nanotags based on rolling circle amplification.
AB  - In this work, we developed a cascade signal amplification strategy for detection
      of IgG antigen by combining the rolling circle amplification (RCA) technique with
      oligonucleotide functionalized carbon dots (CDs), based on a paper-based
      electrochemiluminescence (ECL) origami device (PECLOD) for the first time. In
      this PECLOD, three-dimensional (3D) macroporous Au-paper electrode was fabricated
      and employed as the working electrode for specific and efficient antibodies
      capture. The RCA product containing tandem-repeat sequences could serve as an
      excellent template for periodic assembly of CDs, which presented per protein
      recognition event to numerous CDs tags for ECL readout. Under the optimal
      conditions, the proposed strategy showed remarkable amplification efficiency,
      very little nonspecific adsorption with good stability, reproducibility, and
      accuracy. Using human IgG (H-IgG) as a model protein, the designed strategy was
      successfully demonstrated for the ultrasensitive detection of protein target. The
      results revealed that the strategy exhibited a dynamic response to H-IgG range
      from 1.0 fM to 25 pM with a limit of detection as low as 0.15 fM. Importantly,
      the methodology can be further extended to the detection of other proteins or
      biomarkers.

PMID- 25618374
TI  - Cyclodextrin functionalized graphene-gold nanoparticle hybrids with strong
      supramolecular capability for electrochemical thrombin aptasensor.
AB  - We demonstrate a facile one-pot synthetic strategy for controlled synthesis of
      thio-beta-cyclodextrin functionalized graphene/gold nanoparticles (SH-beta-CD
      Gr/AuNPs) composites using SH-beta-CD as both the dispersant and linker. The
      obtained SH-beta-CD-Gr/AuNPs integrate the excellent electrical properties and
      large surface area of graphene and AuNPs with supramolecular recognition ability
      of CD, which show more effective electron transfer and higher enriched ability
      for the ferrocene probe via the host-guest interaction between CD and ferrocene
      than SH-beta-CD-Gr. In the presence of target, the stronger interaction between
      aptamer and target makes the ferrocene move closer to the electrode surface, thus
      facilitating the electron transfer. Based on this sensing mechanism, a new and
      highly sensitive biosensing concept by the use of SH-beta-CD-Gr/AuNPs as
      enhancing materials is demonstrated for "signal-on" detection of targets
      (thrombin as a model target). This biosensor exhibits a wide linear range for
      thrombin from 1.6*10(-17) M to 8.0*10(-15) M and a very low limit of detection
      5.2*10(-18) M, which is two-order magnitude better than those of SH-beta-CD-Gr
      (the detection linear range from 1.6*10(-15) M to 8.0*10(-13) M and detection
      limit of 1.0*10(-15) M). Our proposed electrochemical aptasensor based on SH-beta
      CD-Gr/AuNPs shows good selectivity against other proteins such as human serum
      albumin, lysozyme and insulin. To the best of our knowledge, the present SH-beta
      CD-Gr/AuNPs hybrids are the most efficient graphene-based electrochemical active
      probes ever reported for biosensors.

PMID- 25618375
TI  - Selective immobilization and detection of DNA on biopolymer supports for the
      design of microarrays.
AB  - DNA immobilization for the manufacturing of microarrays requires sufficient probe
      density, low unspecific binding and high interaction efficiency with
      complementary strands that are detected from solutions. Many of these important
      parameters are affected by the surface chemistry and the blocking steps conducted
      during DNA spotting and hybridization. This work describes an alternative method
      to selectively immobilize probes and to detect DNA on biocompatible, hydrophilic
      cellulose coated supports with low unspecific binding, high selectivity and
      appropriate sensitivity. It takes advantage of a relatively selective adsorption
      of water soluble polysaccharides on a solid cellulose matrix. Single strands of
      DNA were conjugated to this soluble polysaccharide and subsequently micro-spotted
      on solid cellulose thin films that were coated on glass and polymer slides. This
      resulted in adsorptively bound DNA-probes that were used to detect complementary,
      labelled DNA strands with different lengths and sequences by hybridization. The
      interaction of the DNA-conjugates with cellulose surfaces and the selectivity of
      hybridization were investigated by a quartz crystal microbalance with dissipation
      monitoring (QCM-D) and fluorescence scanning. The method of non-covalent
      immobilization of DNA probes on an uncharged, non-reactive, hydrophilic support
      lowers the unspecific binding and the number of handling steps required to
      conduct the experiments for the detection of DNA on microarrays. Simultaneously
      selectivity, hybridization efficiency and detection limits are maintained. 

PMID- 25618376
TI  - An ultrasensitive electrochemical DNA biosensor based on graphene/Au
      nanorod/polythionine for human papillomavirus DNA detection.
AB  - An ultrasensitive electrochemical DNA biosensor for human papillomavirus (HPV)
      detection was developed by electrochemical impedance spectroscopy and
      differential pulse voltammetry. A capture probe was immobilized on a glassy
      carbon electrode modified with graphene/Au nanorod/polythionine (G/Au NR/PT). Two
      auxiliary probes were designed and used to long-range self-assemble DNA
      nanostructure. The target DNA can connect DNA structure to the capture probe on
      the electrode surface. [Ru(phen)3](2+) was selected as a redox indicator for
      amplifying electrochemical signal significantly. Enhanced sensitivity was
      obtained through combining the excellent electric conductivity of G/Au NR/PT
      architecture and the long-range self-assembly DNA nanostructure with the multi
      signal amplification. The DNA biosensor displayed excellent performance for HPV
      DNA detection over the range from 1.0*10(-13) to 1.0*10(-10) mol/L with a
      detection limit of 4.03*10(-14) mol/L. Furthermore, the proposed method can also
      be used for the detection of HPV DNA in human serum samples and provides a
      potential application of DNA detection in clinic research.

PMID- 25618377
TI  - Validation of constitutively expressed bioluminescent Pseudomonas aeruginosa as a
      rapid microbiological quantification tool.
AB  - Whole cell biosensors have been extensively used for monitoring toxicity and
      contamination of various compounds and xenobiotics in environmental biology and
      microbial ecology; their application in the pharmaceutical and cosmetics
      industries has been limited. According to several pharmacopoeias, pharmaceutical
      products must be tested for microbial activity using traditional viable count
      techniques; the use of whole cell microbial biosensors potentially provides an
      alternative, fast, and efficient method. However there is a lack of a validated
      bioluminescence method. Prototype whole cell microbial biosensors have already
      been developed in Pseudomonas aeruginosa ATCC 9027. Validation of the
      bioluminescent strains was performed in accordance with the pharmacopoeia,
      Parenteral Drug Association and International Organisation of Standardisation.
      These strains demonstrated that the bioluminescent method was accurate, precise
      and equivalent, as compared with plate counting at a range of 10(3)-10(7) CFU/mL.
      Percentage recoveries using the bioluminescent method were between 70% and 130%
      for all bioluminescent strains and therefore the bioluminescent method was
      accurate according to the criteria set in PDA technical report 33. The method was
      also more precise (relative standard deviation less than 15%) than the
      traditional plate counting method or the ATP bioluminescent method. The lower
      limit of detection was 10(3) CFU/mL. Two-way ANOVA showed no significant
      difference between the traditional plate counting and the novel bioluminescent
      method for all bioluminescent strains. The bioluminescent constructs
      passed/exceeded pharmacopoeia-specified criteria for range, limit of detection,
      accuracy, precision and equivalence.

PMID- 25618378
TI  - A novel pungency biosensor prepared with fixing taste-bud tissue of rats.
AB  - A novel taste biosensor based on ligand-receptor interaction was developed
      through fixing taste-bud tissues of SD rats to a glassy carbon electrode. Using
      the sodium alginate-starch gel as a fixing agent, taste-bud tissues of SD rats
      were fixed between two nuclear microporous membranes to make a sandwich-type
      sensing membrane. With the taste biosensor, the response current induced by
      capsaicin and gingerol stimulating the corresponding receptors was measured. The
      results showed that the lowest limit of detection of this biosensor to capsaicin
      was 1*10(-13) mol/L and the change rate of response current was the highest at
      the concentration of 9*10(-13) mol/L, indicating that the capsaicin receptor was
      saturated at this point. The lowest limit of detection of this biosensor to
      gingerol was 1*10(-12) mol/L, and the gingerol receptor was saturated when the
      concentration of gingerol was 3*10(-11) mol/L. It was demonstrated that the
      interaction curves of capsaicin and gingerol with their respective receptors
      exhibited high correlation (R(2): 0.9841 and 0.9904). The binding constant and
      dissociation constant of gingerol with its receptor were 1.564*10(-11) and
      1.815*10(-11) respectively, which were all higher than those of capsaicin with
      its receptor (1.249*10(-12) and 2.078*10(-12)). This study, for the first time,
      made it possible to quantitatively determine the interaction of the taste
      receptor and pungent substances with a new biosensor, thus providing a simple
      approach for monitoring pungent substances and investigating the mechanism of
      ligand-receptor interaction.

PMID- 25618379
TI  - One-step synthesis of potassium ferricyanide-doped polyaniline nanoparticles for
      label-free immunosensor.
AB  - A novel, label-free and inherent electroactive redox immunosensor for
      ultrasensitive detection of carcinoembryonic antigen (CEA) was proposed based on
      gold nanoparticles (AuNPs) and potassium ferricyanide-doped polyaniline (FC-PANI)
      nanoparticles. FC-PANI composite was synthesized via oxidative polymerization of
      aniline, using potassium ferricyanide (K3[Fe(CN)6]) as both oxidant and dopant.
      FC-PANI acting as the signal indicator was first fixed on a gold electrode (GE)
      to be the signal layer. Subsequently, the negatively charged AuNPs could be
      adsorbed on the positively charged FC-PANI modified GE surface by electrostatic
      adsorption, and then to immobilize CEA antibody (anti-CEA) for the assay of CEA.
      The CEA concentration was measured through the decrease of amperometric signals
      in the corresponding specific binding of antigen and antibody. The wide linear
      range of the immunosensor was from 1.0 pg mL(-1) to 500.0 ng mL(-1) with a low
      detection limit of 0.1 pg mL(-1) (S/N=3). The proposed method would have a
      potential application in clinical immunoassays with the properties of facile
      procedure, stability, high sensitivity and selectivity.

PMID- 25618380
TI  - Spatial and numerical processing in children with high and low visuospatial
      abilities.
AB  - In the literature on numerical cognition, a strong association between numbers
      and space has been repeatedly demonstrated. However, only a few recent studies
      have been devoted to examine the consequences of low visuospatial abilities on
      calculation processing. In this study, we wanted to investigate whether
      visuospatial weakness may affect pure spatial processing as well as basic
      numerical reasoning. To do so, the performances of children with high and low
      visuospatial abilities were directly compared on different spatial tasks (the
      line bisection and Simon tasks) and numerical tasks (the number bisection, number
      to-position, and numerical comparison tasks). Children from the low visuospatial
      group presented the classic Simon and SNARC (spatial numerical association of
      response codes) effects but showed larger deviation errors as compared with the
      high visuospatial group. Our results, therefore, demonstrated that low
      visuospatial abilities did not change the nature of the mental number line but
      rather led to a decrease in its accuracy. 

PMID- 25618381
TI  - A test to prevent repeat prostate biopsies? Perhaps if the bar of 'clinical
      utility' can be met.

PMID- 25618382
TI  - Sorting out what makes sense in diagnosing, treating prostate cancer.

PMID- 25618383
TI  - Immunotherapy in cancer care: understanding the impact of shifting treatment
      paradigms in the managed care setting.

PMID- 25618384
TI  - Fine print of budget deal does not bode well for SGR overhaul.

PMID- 25618385
TI  - Adjuvant pre- or post-operative chemotherapy does not improve survival in rectal
      cancer.

PMID- 25618386
TI  - Is Medicare ready for oncology clinical pathways?

PMID- 25618387
TI  - Defining, measuring, and paying for the work of oncology patient navigators.

PMID- 25618388
TI  - In cancer and beyond, Washington state making the transition to value-based care.

PMID- 25618389
TI  - Nitrate addition to groundwater impacted by ethanol-blended fuel accelerates
      ethanol removal and mitigates the associated metabolic flux dilution and
      inhibition of BTEX biodegradation.
AB  - A comparison of two controlled ethanol-blended fuel releases under monitored
      natural attenuation (MNA) versus nitrate biostimulation (NB) illustrates the
      potential benefits of augmenting the electron acceptor pool with nitrate to
      accelerate ethanol removal and thus mitigate its inhibitory effects on BTEX
      biodegradation. Groundwater concentrations of ethanol and BTEX were measured 2 m
      downgradient of the source zones. In both field experiments, initial source-zone
      BTEX concentrations represented less than 5% of the dissolved total organic
      carbon (TOC) associated with the release, and measurable BTEX degradation
      occurred only after the ethanol fraction in the multicomponent substrate mixture
      decreased sharply. However, ethanol removal was faster in the nitrate amended
      plot (1.4 years) than under natural attenuation conditions (3.0 years), which led
      to faster BTEX degradation. This reflects, in part, that an abundant substrate
      (ethanol) can dilute the metabolic flux of target pollutants (BTEX) whose
      biodegradation rate eventually increases with its relative abundance after
      ethanol is preferentially consumed. The fate and transport of ethanol and benzene
      were accurately simulated in both releases using RT3D with our general substrate
      interaction module (GSIM) that considers metabolic flux dilution. Since source
      zone benzene concentrations are relatively low compared to those of ethanol (or
      its degradation byproduct, acetate), our simulations imply that the initial focus
      of cleanup efforts (after free-product recovery) should be to stimulate the
      degradation of ethanol (e.g., by nitrate addition) to decrease its fraction in
      the mixture and speed up BTEX biodegradation.

PMID- 25618390
TI  - Oropharyngeal suctioning in neonates immediately after delivery: influence on
      cerebral and peripheral tissue oxygenation.
AB  - BACKGROUND: Routine oropharyngeal suctioning in term vigorous neonates
      immediately after birth is a questionable practice. Current recommendations favor
      suctioning only in the presence of considerable obstruction due to secretions,
      blood or other matter. We aimed to analyze the influence of oropharyngeal
      suctioning on cerebral and peripheral muscle oxygenation in term neonates during
      transition immediately after birth. METHODS: We included term neonates after
      elective cesarean section for this prospective observational study. Oropharyngeal
      suctioning was performed based on the clinicians' judgment of threatening airway
      obstruction. From a total of 138 enrolled neonates, 36 were suctioned and then
      compared to 36 controls matched for gestational age. Heart rate (HR) and
      pre/postductal arterial oxygen saturation (SpO2pre/SpO2post) were measured by
      pulse oximetry. Cerebral (rSO2brain) and pre/postductal peripheral muscle tissue
      oxygenation (rSO2pre/rSO2post) were measured by near infrared spectroscopy during
      the first 15min of life. RESULTS: All neonates in both groups experienced normal
      postnatal transition with normal Apgar scores (Apgar 9/10/10) and with no events
      of apnea or bradycardia induced by suctioning. SpO2pre values were slightly lower
      at 2 and 4min after birth. Suctioning had no main and interaction effect on HR,
      SpO2post, rSO2brain, rSO2pre and rSO2post in the first 15min after birth.
      CONCLUSION: In the present study we were able to show that, in term neonates,
      when correctly indicated, immediate postnatal oropharyngeal suctioning does not
      compromise cerebral and peripheral muscle tissue oxygenation. However, any
      suction maneuver must be performed with caution and strict indication during
      neonatal transition.

PMID- 25618391
TI  - Functional and structural recovery of the injured spinal cord in rats treated
      with gonadotropin-releasing hormone.
AB  - Several studies have shown that gonadotropin-releasing hormone (GnRH) have extra
      pituitary roles, including neurotrophic effects. This study was to evaluate the
      effects of GnRH treatment on the spinal cord injury (SCI) of rats. Ovariectomized
      rats were divided into: sham SCI surgery (Sham), SCI treated with saline solution
      (SCI + SS), and SCI treated with GnRH (SCI + GnRH). The SCI was induced by
      compression. One day after the lesion, SCI + GnRH group was injected with GnRH
      (60 ug/kg/twice/day; i.m.) for 15 days and the other groups with saline solution.
      To kinematic gait analysis, length and velocity of the stride were measured. In
      spinal cord, axonal morphometry and spared white and gray matter were analyzed by
      histochemistry. Protein expression of spinophilin was evaluated by western blot.
      The results showed that, 5 weeks after the injury, the group of animals treated
      with GnRH, significantly increased the length and velocity of the stride compared
      to SCI + SS group and they were similar to Sham group. In spinal cord, GnRH
      treatment increased the number and caliber of nerve axons and in the case of
      white matter, spared tissue was significantly higher than those animals treated
      with saline solution. The expression of spinophilin in spinal cord of SCI + GnRH
      group was slightly increased with respect to those not treated. In conclusion,
      GnRH treatment improves recovery of gait and decreases histopathological damage
      in the injured spinal cord of rat. These findings suggest that GnRH acts as a
      neurotrophic factor and can be used as a potential therapeutic agent for
      treatment of SCI.

PMID- 25618392
TI  - The kinetic theory of active particles as a biological systems approach: comment
      on "On the interplay between mathematics and biology, hallmarks toward a new
      systems biology" by N. Bellomo et al.

PMID- 25618393
TI  - We need more empirical investigations and model validation for a better
      understanding of crime: comment on "Statistical physics of crime: a review" by
      M.R. D'Orsogna and M. Perc.

PMID- 25618394
TI  - Nonlocal models of biological phenomena: comment on "On the interplay between
      mathematical and biology, hallmarks towards a new system biology" by Bellomo,
      Elaiw, Althiabi and Alghamdi.

PMID- 25618395
TI  - Multi-scale problems in complex domains - a mathematical framework for systems
      biology: comment on "On the interplay between mathematics and biology, hallmarks
      toward a new systems biology" by N. Bellomo, A. Elaiw, A.M. Althiabi and M.A.
      Alghamdi.

PMID- 25618396
TI  - From systems biology to analytic problems: comment on the paper "On the interplay
      between mathematics and biology, hallmarks toward a new systems biology" by N.
      Bellomo et al.

PMID- 25618397
TI  - Toward computational crime prediction: comment on "Statistical physics of crime:
      a review" by M.R. D'Orsogna and M. Perc.

PMID- 25618398
TI  - Inference and representations of hand actions through grasping synergies: comment
      on "Grasping synergies: a motor-control approach to the mirror neuron mechanism"
      by D'Ausilio, Bartoli, and Maffongelli.

PMID- 25618399
TI  - Emergency right hepatectomy after laparoscopic tru-cut liver biopsy.
AB  - BACKGROUND: Liver biopsy is a common procedure usually required for final
      pathologic diagnosis of different liver diseases. Morbidity following tru-cut
      biopsy is uncommon, with bleeding complications generally self-limited. Few cases
      of major hemorrhage after liver biopsies have been reported, but to our
      knowledge, no cases of emergency hepatectomy following a tru-cut liver biopsy
      have been reported previously. PRESENTATION OF CASE: We report the case of a 38
      years-old woman who presented with an intrahepatic arterial bleeding after a tru
      cut liver biopsy under direct laparoscopic visualization, initially controlled by
      ligation of the right hepatic artery and temporary liver packing. On tenth
      postoperative day, she developed a pseudo-aneurysm of the anterior branch of the
      right hepatic artery, evolving with massive bleeding that was not amenable to
      control by endovascular therapy. Therefore, an emergency right hepatectomy had to
      be performed in order to stop the bleeding. The patient achieved hemodynamic
      stabilization, but developed a biliary fistula from the liver surface, refractory
      to non-operative treatment. In consequence, a Roux-Y hepatico-jejunostomy was
      performed at third month, with no further complications. DISCUSSION: Bleeding
      following tru-cut biopsy is a rare event. To our knowledge, this is the first
      report of an emergency hepatectomy due to hemorrhage following liver biopsy.
      Risks and complications of liver biopsy are revised. CONCLUSION: Care must be
      taken when performing this kind of procedures and a high level of suspicion
      regarding this complication should be taken in count when clinical/hemodynamic
      deterioration occurs after these procedures.

PMID- 25618400
TI  - Treatment of an aneurysm of the celiac artery arising from a celiomesenteric
      trunk. Report of a case.
AB  - INTRODUCTION: Visceral artery aneurysms (VAA) are rare, frequently present as a
      life-threatening emergency and are often fatal. The celiacomesenteric trunk
      (CMT), a common origin of the celiac trunk (CT) and the superior mesenteric
      artery (SMA) from abdominal aorta, is quite rare. Aneurysms that involve this
      celiomesenteric anomaly are even rarer and in the last 32 years have been
      reported in only 20 cases in the literature. PRESENTATION OF CASE: We describe a
      case with 30mm aneurysm arising from a CMT. In general, an aneurysm that is 20mm
      or greater in size is considered to be significant enough to warrant treatment.
      Abdominal VAA sometimes can be treated with low-invasive procedures: our patient
      required open surgical repair with the celiac artery replanted on to the aorta.
      DISCUSSION: The clinical course was complicated only by an increase of hepatic
      cytolysis enzymes, and by a low output pancreatic fistula, treated
      conservatively. The patient was discharged on the fifteenth postoperative day.
      One month after discharge, imaging revealed a good patency of all reconstructed
      arteries. In the subsequent 36-month follow-up period, the patient reported no
      clinical episodes. CONCLUSION: Our finding of a very rare case of a
      celiomesenteric anomaly with a concurrent aneurysm is extremely rare (20 cases in
      word literature in the last 32 years). The feasibility of the endovascular
      approach for aneurysms originating from the common celiomesenteric trunk depends
      mainly on aneurysmal location, diameter and neck size. In case of specific unfit
      anatomy, a careful surgical treatment can ensure the best results.

PMID- 25618401
TI  - Quetiapine attenuates glial activation and proinflammatory cytokines in APP/PS1
      transgenic mice via inhibition of nuclear factor-kappaB pathway.
AB  - BACKGROUND: In Alzheimer's disease, growing evidence has shown that uncontrolled
      glial activation and neuroinflammation may contribute independently to
      neurodegeneration. Antiinflammatory strategies might provide benefits for this
      devastating disease. The aims of the present study are to address the issue of
      whether glial activation and proinflammatory cytokine increases could be
      modulated by quetiapine in vivo and in vitro and to explore the underlying
      mechanism. METHODS: Four-month-old amyloid precursor protein (APP) and presenilin
      1 (PS1) transgenic and nontransgenic mice were treated with quetiapine (5mg/kg/d)
      in drinking water for 8 months. Animal behaviors, total Abeta levels, and glial
      activation were evaluated by behavioral tests, enzyme-linked immunosorbent assay,
      immunohistochemistry, and Western blot accordingly. Inflammatory cytokines and
      the nuclear factor kappa B pathway were analyzed in vivo and in vitro. RESULTS:
      Quetiapine improves behavioral performance, marginally affects total Abeta40 and
      Abeta42 levels, attenuates glial activation, and reduces proinflammatory
      cytokines in APP/PS1 mice. Quetiapine suppresses Abeta1-42-induced activation of
      primary microglia by decresing proinflammatory cytokines. Quetiapine inhibits the
      activation of nuclear factor kappa B p65 pathway in both transgenic mice and
      primary microglia stimulated by Abeta1-42. CONCLUSIONS: The antiinflammatory
      effects of quetiapine in Alzheimer's disease may be involved in the nuclear
      factor kappa B pathway. Quetiapine may be an efficacious and promising treatment
      for Alzheimer's disease targeting on neuroinflammation.

PMID- 25618402
TI  - Cannabidiol attenuates sensorimotor gating disruption and molecular changes
      induced by chronic antagonism of NMDA receptors in mice.
AB  - BACKGROUND: Preclinical and clinical data suggest that cannabidiol (CBD), a major
      non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like
      effects. However, the antipsychotic properties of repeated CBD treatment have
      been poorly investigated. Behavioral changes induced by repeated treatment with
      glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as
      an animal model of schizophrenia-like signs. In the present study, we evaluated
      if repeated treatment with CBD would attenuate the behavioral and molecular
      modifications induced by chronic administration of one of these antagonists, MK
      801. METHODS: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1,
      0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last
      injection, animals were submitted to the prepulse inhibition (PPI) test. After
      that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would
      attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28
      days). CBD treatment began on the 6th day after the start of MK-801
      administration and continued until the end of the treatment. Immediately after
      the PPI, the mice brains were removed and processed to evaluate the molecular
      changes. We measured changes in FosB/DeltaFosB and parvalbumin (PV) expression, a
      marker of neuronal activity and a calcium-binding protein expressed in a subclass
      of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR
      GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those
      induced by the atypical antipsychotic clozapine. RESULTS: MK-801 administration
      at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with
      CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased
      FosB/DeltaFosB expression and decreased PV expression in the medial prefrontal
      cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All
      the molecular changes were attenuated by CBD. CBD by itself did not induce any
      effect. Moreover, CBD effects were similar to those induced by repeated clozapine
      treatment. CONCLUSIONS: These results indicate that repeated treatment with CBD,
      similar to clozapine, reverses the psychotomimetic-like effects and attenuates
      molecular changes observed after chronic administration of an NMDAR antagonist.
      These data support the view that CBD may have antipsychotic properties.

PMID- 25618403
TI  - Induction of cannabinoid- and N-methyl-D-aspartate receptor-mediated long-term
      depression in the nucleus accumbens and dorsolateral striatum is region and age
      dependent.
AB  - BACKGROUND: The adolescent brain is sensitive to experience-dependent plasticity
      and might be more vulnerable than the adult brain to the effects of some drugs of
      abuse. The factors that contribute to these differences are not fully identified.
      We have examined the ability of cannabinoids to induce a form of synaptic
      plasticity, long-term depression, in the nucleus accumbens and dorsolateral
      striatum of adolescent and adult mice. METHODS: We measured field excitatory
      postsynaptic potentials/population spikes in brain slices. RESULTS: We found that
      the cannabinoid receptor agonist WIN 55,212-2 (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      mesylate) induced long-term depression in the nucleus accumbens of adolescent but
      not adult mice and failed to induce long-term depression in the dorsolateral
      striatum of adolescent or adult mice. Similar results were obtained with the
      group I metabotropic glutamate receptor agonist (S)-3,5- dihydroxyphenylglycine,
      which has previously been shown to promote the release of endocannabinoids. These
      age-related differences were associated with reduced protein levels of the
      cannabinoid type 1 receptor and metabotropic glutamate receptor 1 in adult
      nucleus accumbens and dorsolateral striatum and with an increased tone of
      endocannabinoids in the dorsolateral striatum of adult mice. We also found that N
      methyl-D-aspartate receptor-dependent long-term depression, which was induced in
      the nucleus accumbens of adolescent mice, was blunted in adult mice, possibly
      because of decreased levels of GluN1, the obligatory subunit of N-methyl-D
      aspartate receptors. CONCLUSIONS: This study identifies region- and age-specific
      differences in the ability of endogenous and exogenous cannabinoids, and of N
      methyl-D-aspartate receptors, to induce long-term depression in the striatal
      complex. These observations might contribute to a better understanding of the
      increased sensitivity of the adolescent brain to drug induced-plasticity.

PMID- 25618405
TI  - Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for
      Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or
      to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure.
AB  - BACKGROUND: Chronic amphetamine treatment decreases cocaine consumption in
      preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine
      is an amphetamine prodrug in which L-lysine is conjugated to the terminal
      nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active
      metabolites due to slower onsets and longer durations of action; however,
      lisdexamfetamine treatment's efficacy in decreasing cocaine consumption is
      unknown. METHODS: This study compared lisdexamfetamine and d-amphetamine effects
      in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination
      procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus
      food choice self-administration procedure. RESULTS: In the cocaine-discrimination
      procedure, lisdexamfetamine (0.32-3.2mg/kg, i.m.) substituted for cocaine with
      lower potency, slower onset, and longer duration of action than d-amphetamine
      (0.032-0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an
      inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was
      related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In
      the choice procedure, cocaine (0-0.1mg/kg/injection, i.v.) and food (1g banana
      flavored pellets) were concurrently available, and cocaine maintained a dose
      dependent increase in cocaine choice under baseline conditions. Treatment for 7
      consecutive days with lisdexamfetamine (0.32-3.2mg/kg/day, i.m.) or d-amphetamine
      (0.032-0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in
      cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection
      cocaine. CONCLUSIONS: Lisdexamfetamine has a slower onset and longer duration of
      action than amphetamine but retains amphetamine's efficacy to reduce the choice
      of cocaine in rhesus monkeys. These results support further consideration of
      lisdexamfetamine as an agonist-based medication candidate for cocaine addiction.

PMID- 25618404
TI  - Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence
      for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution
      of the Endocannabinoid System.
AB  - BACKGROUND: Inducible or neuronal nitric oxide synthase gene deletion increases
      or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and
      endocannabinoids interact to modulate defensive behavior, the former effect could
      involve a compensatory increase in basal brain nitric oxide synthase activity
      and/or changes in the endocannabinoid system. Thus, we investigated the
      expression and extinction of contextual fear conditioning of inducible nitric
      oxide knockout mice and possible involvement of endocannabinoids in these
      responses. METHODS: We evaluated the effects of a preferential neuronal nitric
      oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and
      mRNA changes of nitrergic and endocannabinoid systems components in the medial
      prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of
      URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes
      the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist,
      and AM281, a selective CB1 antagonist, on contextual fear conditioning were also
      evaluated. RESULTS: Contextual fear conditioning expression was similar in wild
      type and knockout mice, but the latter presented extinction deficits and
      increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7
      Nitroindazol decreased fear expression and facilitated extinction in wild-type
      and knockout mice. URB597 decreased fear expression in wild-type and facilitated
      extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild
      type mice. Nonconditioned knockout mice showed changes in the mRNA expression of
      nitrergic and endocannabinoid system components in the medial prefrontal cortex
      and hippocampus that were modified by fear conditioning. CONCLUSION: These data
      reinforce the involvement of the nitric oxide and endocannabinoids (anandamide)
      in stress-related disorders and point to a deregulation of the endocannabinoid
      system in situations where nitric oxide signaling is increased.

PMID- 25618406
TI  - Tetramethylpyrazine Produces Antidepressant-Like Effects in Mice Through
      Promotion of BDNF Signaling Pathway.
AB  - BACKGROUND: Current antidepressants are clinically effective only after several
      weeks of administration. Tetramethylpyrazine (TMP) is an identified component of
      Ligusticum wallichii with neuroprotective effects. Here, we investigated the
      antidepressant effects of TMP in mice models of depression. METHODS:
      Antidepressant effects of TMP were first detected in the forced swim test (FST)
      and tail suspension test (TST), and further assessed in the chronic social defeat
      stress (CSDS) model. Changes in the brain-derived neurotrophic factor (BDNF)
      signaling pathway and in hippocampal neurogenesis after CSDS and TMP treatment
      were then investigated. A tryptophan hydroxylase inhibitor and BDNF signaling
      inhibitors were also used to determine the mechanisms of TMP. RESULTS: TMP
      exhibited potent antidepressant effects in the FST and TST without affecting
      locomotor activity. TMP also prevented the CSDS-induced symptoms. Moreover, TMP
      completely restored the CSDS-induced decrease of BDNF signaling pathway and
      hippocampal neurogenesis. Furthermore, a blockade of the BDNF signaling pathway
      prevented the antidepressant effects of TMP, while TMP produced no influence on
      the monoaminergic system. CONCLUSIONS: In conclusion, these data provide the
      first evidence that TMP has antidepressant effects, and this was mediated by
      promoting the BDNF signaling pathway.

PMID- 25618408
TI  - PI3Kalpha is essential for the recovery from Cre/tamoxifen cardiotoxicity and in
      myocardial insulin signalling but is not required for normal myocardial
      contractility in the adult heart.
AB  - AIMS: Genetic mouse models have yielded conflicting conclusions about the role of
      PI3Kalpha in heart physiology: specifically, the question of whether PI3Kalpha
      has a direct role in regulating myocardial contractility. This has led to
      concerns that PI3K inhibitors currently in clinical trials for cancer may
      potentiate cardiotoxicity. Here we seek to clarify the role of PI3Kalpha in
      normal heart physiology and investigate changes in related signalling pathways.
      METHODS AND RESULTS: Targeted deletion of PI3Kalpha and PI3Kbeta in the heart
      with a tamoxifen-dependent Cre recombinase transgene caused transient heart
      dysfunction in all genotypes, but only PI3Kalpha deletion prevented functional
      recovery. Reduction in tamoxifen dosing allowed for maintained gene deletion
      without any cardiomyopathy, possibly through activation of survival signalling
      through the related ERK pathway. Similarly, mice with PI3Kalpha deletion induced
      by constitutively active Cre recombinase had normal heart function. Insulin
      mediated activation of Akt, a marker of PI3Kalpha activity, was impaired with
      increased ERK1/2 activation in PI3Kalpha mutant hearts. Pharmacological
      inhibition of PI3Kalpha with BYL-719 also caused impaired insulin signalling in
      murine and human cardiomyocytes as well as in vivo in mice, with increased
      fasting blood glucose levels, but did not affect myocardial contractility as
      determined by echocardiography and invasive pressure-volume loop analysis.
      CONCLUSION: Our results show that PI3Kalpha does not directly regulate myocardial
      contractility, but is required for recovery from tamoxifen/Cre toxicity. The
      important role for PI3Kalpha in insulin signalling and recovery from
      tamoxifen/Cre toxicity justifies caution when using PI3Kalpha inhibitors in
      combination with other cardiovascular comorbidities and cardiotoxic compounds in
      cancer patients.

PMID- 25618407
TI  - Telomerase dysregulation in the hippocampus of a rat model of depression:
      normalization by lithium.
AB  - BACKGROUND: Telomeres are protective DNA-protein complexes at the ends of each
      chromosome, maintained primarily by the enzyme telomerase. Shortening of the
      blood leukocyte telomeres is associated with aging, several chronic diseases, and
      stress, eg, major depression. Hippocampus is pivotal in the regulation of
      cognition and mood and the main brain region of telomerase activity. Whether
      there is telomere dysfunction in the hippocampus of depressed subjects is
      unknown. Lithium, used in the treatment and relapse prevention of mood disorders,
      was found to protect against leukocyte telomere shortening in humans, but the
      mechanism has not been elucidated. To answer the questions whether telomeres are
      shortened and the telomerase activity changed in the hippocampus and whether
      lithium could reverse the process, we used a genetic model of depression, the
      Flinders Sensitive Line rat, and treated the animals with lithium. METHODS:
      Telomere length, telomerase reverse transcriptase (Tert) expression, telomerase
      activity, and putative mediators of telomerase activity were investigated in the
      hippocampus of these animals. RESULTS: The naive Flinders Sensitive Line had
      shorter telomere length, downregulated Tert expression, reduced brain-derived
      neurotrophic factor levels, and reduced telomerase activity compared with the
      Flinders Resistant Line controls. Lithium treatment normalized the Tert
      expression and telomerase activity in the Flinders Sensitive Line and upregulated
      beta-catenin. CONCLUSION: This is the first report showing telomere dysregulation
      in hippocampus of a well-defined depression model and restorative effects of
      lithium treatment. If replicated in other models of mood disorder, the findings
      will contribute to understanding both the telomere function and the mechanism of
      lithium action in hippocampus of depressed patients.

PMID- 25618409
TI  - Cardiomyocyte-specific expression of CYP2J2 prevents development of cardiac
      remodelling induced by angiotensin II.
AB  - AIMS: Cardiac remodelling is one of the key pathological changes that occur with
      cardiovascular disease. Previous studies have demonstrated the beneficial effects
      of CYP2J2 expression on cardiac injury. In the present study, we investigated the
      effects of cardiomyocyte-specific CYP2J2 expression and EET treatment on
      angiotensin II-induced cardiac remodelling and sought to determine the underlying
      molecular mechanisms involved in this process. METHODS AND RESULTS: Eight-week
      old mice with cardiomyocyte-specific CYP2J2 expression (alphaMHC-CYP2J2-Tr) and
      wild-type (WT) control mice were treated with Ang-II. Ang-II treatment of WT mice
      induced changes in heart morphology, cardiac hypertrophy and dysfunction, as well
      as collagen accumulation; however, cardiomyocyte-specific expression of CYP2J2
      attenuated these effects. The cardioprotective effects observed in alpha-MHC
      CYP2J2-Tr mice were associated with peroxisome proliferator-activated receptor
      (PPAR)-gamma activation, reduced oxidative stress, reduced NF-kappaB p65 nuclear
      translocation, and inhibition of TGF-beta1/smad pathway. The effects seen with
      cardiomyocyte-specific expression of CYP2J2 were partially blocked by treatment
      with PPAR-gamma antagonist GW9662. In in vitro studies, 11,12-EET(1 MUmol/L)
      treatment attenuated cardiomyocyte hypertrophy and remodelling-related protein
      (collagen I, TGF-beta1, TIMP1) expression by inhibiting the oxidative stress
      mediated NF-kappaB pathway via PPAR-gamma activation. Furthermore, conditioned
      media from neonatal cardiomyocytes treated with 11,12-EET inhibited activation of
      cardiac fibroblasts and TGF-beta1/smad pathway. CONCLUSION: Cardiomyocyte
      specific expression of CYP2J2 or treatment with EETs protects against cardiac
      remodelling by attenuating oxidative stress-mediated NF-kappaBp65 nuclear
      translocation via PPAR-gamma activation.

PMID- 25618411
TI  - Real-time assessment of intestinal viability using indocyanine green fluorescent
      imaging (with video).

PMID- 25618412
TI  - PTRF is associated with caveolin 1 at the time of receptivity: but SDPR is absent
      at the same time.
AB  - The plasma membrane of uterine epithelial cells undergoes a number of changes
      during early pregnancy. The changes in the basolateral membrane at the time of
      implantation in particular change from being smooth to highly tortuous in
      morphology, along with a dramatic increase in the number of morphological
      caveolae at this time. The major protein of caveolar membranes is caveolin, and
      previous studies have shown that RNA pol I transcription factor (PTRF) and serum
      deprivation protein response (SDPR) are the two members of the cavin protein
      family. These proteins are known to be involved in caveolae biogenesis, where
      they directly bind to cholesterol and lipids and have been reported to promote
      membrane curvature. As there is an increase in membrane tortuosity and caveolae
      at the time of implantation, this study investigated PTRF and SDPR to explore the
      possible roles that they play in the morphology of the uterine epithelium during
      early pregnancy. PTRF protein abundance did not change in uterine epithelial
      cells during early pregnancy or in response to ovarian hormones. At the time of
      implantation in uterine epithelial cells, PTRF co-immunoprecipitated with
      caveolin 1, thereby demonstrating an association with caveolin-1 at the basal
      plasma membrane in caveolae. SDPR protein was observed to be present only at the
      time of fertilisation, and also under the influence of oestrogen alone, where a
      cytoplasmic localisation in uterine epithelial cells was observed. The
      localisation and expression PTRF and SDPR in uterine epithelial cells during
      early pregnancy suggest that they have roles in the maintenance of lipids and
      cholesterol in the plasma membrane. PTRF and lack of SDPR may contribute not only
      to the morphology of the basal plasma membrane as observed at the time of
      implantation, but also to the maintenance of epithelial polarity during early
      pregnancy.

PMID- 25618413
TI  - Matrix metalloproteinases and bronchiolitis obliterans: Wrapping the enigma in a
      riddle.

PMID- 25618410
TI  - Modelling sarcomeric cardiomyopathies in the dish: from human heart samples to
      iPSC cardiomyocytes.
AB  - One of the obstacles to a better understanding of the pathogenesis of human
      cardiomyopathies has been poor availability of heart-tissue samples at early
      stages of disease development. This has possibly changed by the advent of patient
      derived induced pluripotent stem cell (hiPSC) from which cardiomyocytes can be
      derived in vitro. The main promise of hiPSC technology is that by capturing the
      effects of thousands of individual gene variants, the phenotype of differentiated
      derivatives of these cells will provide more information on a particular disease
      than simple genotyping. This article summarizes what is known about the 'human
      cardiomyopathy or heart failure phenotype in vitro', which constitutes the
      reference for modelling sarcomeric cardiomyopathies in hiPSC-derived
      cardiomyocytes. The current techniques for hiPSC generation and cardiac myocyte
      differentiation are briefly reviewed and the few published reports of hiPSC
      models of sarcomeric cardiomyopathies described. A discussion of promises and
      challenges of hiPSC-modelling of sarcomeric cardiomyopathies and individualized
      approaches is followed by a number of questions that, in the view of the authors,
      need to be answered before the true potential of this technology can be
      evaluated. 

PMID- 25618414
TI  - Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1
      Vpr and SIVagm Vpr.
AB  - Vpr and Vpx are a group of highly related accessory proteins from primate
      lentiviruses. Despite the high degree of amino acid homology within this group,
      these proteins can be highly divergent in their functions. In this work, we
      constructed chimeric and mutant proteins between HIV-1 and SIVagm Vpr in order to
      better understand the structure-function relationships. We tested these
      constructs for their abilities to induce G2 arrest in human cells and to degrade
      agmSAMHD1 and Mus81. We found that the C-terminus of HIV-1 Vpr, when transferred
      onto SIVagm Vpr, provides the latter with the de novo ability to induce G2 arrest
      in human cells. We confirmed that HIV-1 Vpr induces degradation of Mus81
      although, surprisingly, degradation is independent and genetically separable from
      Vpr's ability to induce G2 arrest.

PMID- 25618415
TI  - Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine
      alone in metastatic pancreatic cancer: a randomized phase II study.
AB  - BACKGROUND: Single-agent gemcitabine (GEM) has been considered for many years as
      the standard first-line treatment for advanced pancreatic cancer. However,
      recently, several studies reported encouraging activity and good tolerability for
      some combination regimens. Considering the apparently non-overlapping toxicity
      and the proved individual efficacy of GEM, oxaliplatin (L-OHP), and capecitabine
      (CAP), this randomized phase II study compared the activity and safety of the
      combination GEM, L-OHP, and CAP (GEMOXEL) versus GEM alone, in patients with
      metastatic pancreatic cancer. MATERIALS AND METHODS: The treatment in GEMOXEL arm
      consisted of GEM 1,000 mg/m(2) as a 30-min intravenous infusion on days 1, 8, 15,
      22, L-OHP 100 mg/m(2) i.v. on day 2, and CAP 1,500 mg/m(2)/day in two divided
      doses on days 1-14, every 21 days (one cycle). In both treatment groups, GEM was
      administered weekly for seven consecutive weeks followed by 1-week rest for the
      first 8 weeks, and thereafter, GEM was continued on days 1, 8, 15, every 28 days.
      Chemotherapy was administered until disease progression or unacceptable toxicity.
      RESULTS: Sixty-seven patients were enrolled in the study. Thirty-four were
      randomly assigned to GEMOXEL and 33 to GEM. At 4 months, disease control rate was
      79.4% with GEMOXEL versus 45.4 % with GEM (p = 0.004). The median progression
      free survival was 6.8 months (95% CI 5.3-7.3 months) in GEMOXEL arm and 3.7
      months (95% CI 2.9-4.7 months) in GEM arm (p < 0.001). The median OS was 11.9
      months (95% CI 10.6-12.9 months) in GEMOXEL arm and 7.1 months (95% CI 5.5-9.1
      months) in GEM arm (p < 0.001). Hematologic and non-hematologic toxicity was more
      severe with combination chemotherapy, yet still tolerable. No grade 4 adverse
      events were observed with either regimen. CONCLUSION: GEMOXEL regimen seemed to
      be safe and more efficient than the standard therapy with GEM alone in the
      treatment of metastatic pancreatic cancer.

PMID- 25618416
TI  - Biological evaluation of 4,5-diarylimidazoles with hydroxamic acid appendages as
      novel dual mode anticancer agents.
AB  - PURPOSE: New (4-aryl-1-methylimidazol-5-yl)cinnamoylhydroxamic acids were
      prepared as potential dual mode anticancer agents combining the antivascular
      effect of the 4,5-diarylimidazole moiety and the histone deacetylases (HDAC)
      inhibition by the cinnamoyl hydroxamate. METHODS: Their antiproliferative
      activity against a panel of primary cells and cancer cell lines was determined by
      MTT assays and their apoptosis induction by caspase-3 activation. Their ability
      to reduce the activity of HDAC was measured by enzymatic assays and Western blot
      analyses of cellular HDAC substrates. Additional effects on cancer cell migration
      were ascertained via immunofluorescence staining of cytoskeleton components and
      three-dimensional migration assays. The chorioallantoic membrane assay was used
      as an in vivo model to assess their antiangiogenic properties. RESULTS: The 4
      phenyl- and 4-(p-methoxyphenyl)-imidazole derivatives had a greater
      antiproliferative and apoptosis inducing effect in a variety of cancer cell lines
      when compared with the approved HDAC inhibitor SAHA, and most distinctly so in
      non-malignant human umbilical vein endothelial cells. Like SAHA, both compounds
      acted as pan-HDAC inhibitors. In 518A2 melanoma cells, they led to
      hyperacetylation of histones and of the cytoplasmic HDAC6 substrate alpha
      tubulin. As a consequence, they inhibited the migration and invasion of these
      cells in transwell invasion assays. In keeping with its pronounced impact on
      endothelial cells, the 4-phenyl-imidazole derivative also inhibited the growth
      and sprouting of blood vessels in the chorioallantoic membrane of fertilized hen
      eggs. CONCLUSIONS: The 4-phenyl- and 4-(p-methoxyphenyl)-imidazole compounds
      combine the antivascular effects of 4,5-diarylimidazoles with HDAC inhibition by
      cinnamoyl hydroxamates and show additional antimetastatic activity. They are
      promising candidates for pleiotropic HDAC inhibitors.

PMID- 25618417
TI  - A novel killer protein from Pichia kluyveri isolated from an Algerian soil:
      purification and characterization of its in vitro activity against food and
      beverage spoilage yeasts.
AB  - A novel killer protein (Pkkp) secreted by a Pichia kluyveri strain isolated from
      an Algerian soil was active against food and beverage spoilage yeasts of the
      genera Dekkera, Kluyveromyces, Pichia, Saccharomyces, Torulaspora,
      Wickerhamomyces and Zygosaccharomyces. After purification by gel filtration
      chromatography Pkkp revealed an apparent molecular mass of 54 kDa with SDS-PAGE.
      Minimum inhibitory concentrations (MICs) of purified Pkkp exhibited a high in
      vitro activity against Dekkera bruxellensis (MICs from 64,000- to 256,000-fold
      lower than that exhibited by potassium metabisulphite) and Saccharomyces
      cerevisiae (MICs from 32,000- to 64,000- fold lower than potassium sorbate). No
      in vitro synergistic interactions (calculated by FIC index - Sigma FIC) were
      observed when Pkkp was used in combination with potassium metabisulphite,
      potassium sorbate, or ethanol. Pkkp exhibited a dose-response effect against D.
      bruxellensis and S. cerevisiae in a low-alcoholic drink and fruit juice,
      respectively. The results of the present study suggest that Pkkp could be
      proposed as a novel food-grade compound useful for the control of food and
      beverage spoilage yeasts. 

PMID- 25618418
TI  - Effects of increased wholegrain consumption on immune and inflammatory markers in
      healthy low habitual wholegrain consumers.
AB  - PURPOSE: Wholegrain (WG) consumption is associated with reduced risk of
      cardiovascular disease, but clinical data on inflammation and immune function is
      either conflicting or limited. The objective of this study was to assess the
      impact of increasing WG consumption to at least 80 g/day on markers of
      inflammation and glucose metabolism and on phenotypic and functional aspects of
      the immune system, in healthy, middle-aged adults with low habitual WG intake.
      METHODS: Subjects consumed a diet high in WG (>80 g/day) or low in WG (<16 g/day,
      refined grain diet) in a crossover study, with 6-week intervention periods,
      separated by a 4-week washout. Adherence to the dietary regimes was achieved by
      dietary advice and provision of a range of food products, with compliance
      verified by analysis of plasma alkylresorcinols (ARs). RESULTS: On the WG
      intervention, WG consumption reached 168 g/day (P < 0.001), accompanied by an
      increase in plasma ARs (P < 0.001) and fibre intake (P < 0.001), without
      affecting other aspects of dietary intake. On the WG arm, there were trends for
      lower ex vivo activation of CD4(+) T cells and circulating concentrations of IL
      10, C-reactive protein, C-peptide, insulin and plasminogen activator inhibitor-1.
      The percentage of CD4(+) central memory T cells and circulating levels of adipsin
      tended to increase during the WG intervention. CONCLUSIONS: Despite the dramatic
      increase in WG consumption, there were no effects on phenotypic or functional
      immune parameters, markers of inflammation or metabolic markers.

PMID- 25618419
TI  - Vector analysis of low to moderate astigmatism with small incision lenticule
      extraction (SMILE): results of a 1-year follow-up.
AB  - BACKGROUND: To evaluate the refractive outcomes for the correction of low to
      moderate astigmatism up to 1 year following small incision lenticule extraction
      (SMILE) surgery. METHODS: This retrospective study enrolled 98 eyes from 98
      patients who underwent SMILE surgery for the correction of myopia and
      astigmatism. Only right eyes were included in this study to avoid the bias of
      orientation errors. The vector method was used to analyze the outcomes of
      astigmatism at 1 month, 6 months and 12 months after the procedure, including the
      double-angle plots, correction index (CI), index of success (IOS), angle of error
      (AofE) and magnitude of error (MofE). The effectiveness, safety, stability and
      predictability were also investigated during the 12-month follow-up. RESULTS: The
      preoperative cylinder ranged from -2.75 D to -0.25 D (average of -0.90+/-0.68 D),
      and the mean postoperative cylinder values were -0.24+/-0.29 D, -0.24+/-0.29 D,
      and -0.20+/-0.27 D at 1 month, 6 months, and 12 months, respectively. The mean
      astigmatism in vector form was -0.14 D*27.19 degrees  at 1 month, -0.13 D*27.29
      degrees  at 6 months, and -0.10 D*28.63 degrees  at 12 months after surgery. The
      CI was 1.00+/-0.32 and IOS was 0.29+/-0.44 at the 12-month follow-up. Significant
      negative correlations were found between the CI and absolute target induced
      astigmatism (TIA) value, and positive correlations were found between the IOS and
      absolute AofE value (P<0.05). The MofE was limited within +/-1.00 D at the 12
      month follow-up. Fifty-six eyes (57.1%) gained one line in corrected distance
      visual acuity (CDVA) and five eyes (5.1%) gained two lines. There were no
      significant differences observed in the refractive outcomes among time points.
      CONCLUSIONS: SMILE surgery was effective and safe in correcting low to moderate
      astigmatism, and stable refractive outcomes were observed at the long-term follow
      up. The undercorrection of astigmatism could possibly be influenced by attempted
      astigmatism correction preoperatively, the axis rotation during the surgery or
      wound healing postoperatively. This study suggested that nomograms should be
      adjusted in correcting astigmatism with SMILE surgery.

PMID- 25618421
TI  - Update of the telavancin activity in vitro tested against a worldwide collection
      of Gram-positive clinical isolates (2013), when applying the revised
      susceptibility testing method.
AB  - A revised broth microdilution susceptibility testing method for telavancin was
      approved by the Food and Drug Administration (FDA). Telavancin activity was
      assessed against Gram-positive pathogens collected worldwide (2013) using the
      revised method. A total of 12,346 isolates from 90 sites were included as part of
      the Telavancin International Surveillance Program for the Americas, Europe, and
      Asia-Pacific. Telavancin had MIC50 and MIC90 values of 0.03 and 0.06 MUg/mL,
      respectively, against staphylococci, regardless of methicillin susceptibility,
      and inhibited all Staphylococcus aureus at <=0.12 MUg/mL (revised FDA
      breakpoint). Telavancin was 8-fold more active than daptomycin (MIC50/90,
      0.25/0.5 MUg/mL) and 16- to 32-fold more active than vancomycin (MIC50/90, 1/1
      MUg/mL) and linezolid (MIC50/90, 1/1 MUg/mL) against methicillin-resistant S.
      aureus. All 692 vancomycin-susceptible Enterococcus faecalis were inhibited by
      telavancin (MIC50/90, 0.12/0.12 MUg/mL) at <=0.25 MUg/mL (FDA breakpoint), except
      for 1 strain (MIC, 0.5 MUg/mL). All Enterococcus faecium and E. faecalis with
      telavancin MIC values of >=0.5 and >=1 MUg/mL, respectively, had a VanA
      phenotype. A comparison data analysis based on the MIC90 demonstrated that
      telavancin was at least 8-fold more potent than comparators against vancomycin
      susceptible enterococci. Streptococci showed telavancin MIC50 values of <=0.015
      MUg/mL, except for Streptococcus agalactiae (MIC50, 0.03 MUg/mL). These in vitro
      results obtained by the recently approved susceptibility testing method establish
      a new benchmark of telavancin activity worldwide.

PMID- 25618420
TI  - Early cytokine and antibody responses against Coxiella burnetii in aerosol
      infection of BALB/c mice.
AB  - Coxiella burnetii, a Gram-negative intracellular bacterium, can give rise to Q
      fever in humans and is transmitted mainly by inhalation of infected aerosols from
      animal reservoirs. Serology is commonly used to diagnose Q fever, but the early
      cellular immune response-i.e., C. burnetii-specific interferon gamma (IFN-gamma)
      production in response to antigen challenge-might be an additional diagnostic.
      Detection of IFN-gamma responses has been used to identify past and chronic Q
      fever infections, but the IFN-gamma response in acute Q fever has not been
      described. By challenging immunocompetent BALB/c mice with aerosols containing
      phase I C. burnetii, the timing and extent of IFN-gamma recall responses were
      evaluated in an acute C. burnetii infection. Other cytokines were also measured
      in an effort to identify other potential diagnostic markers. The data show that
      after initial expansion of bacteria first in lungs and then in other tissues, the
      infection was cleared from day 10 onwards as reflected by the decreasing number
      of bacteria. The antigen-induced IFN-gamma production by splenocytes coincided
      with emergence of IgM phase II antibodies at day 10 postinfection and preceded
      appearance of IgG antibodies. This was accompanied by the production of
      proinflammatory cytokines including interleukin (IL) 6, keratinocyte-derived
      cytokine, and IFN-gamma-induced protein 10, followed by monocyte chemotactic
      protein 1, but not by IL-1beta and tumor necrosis factor alpha, and only very low
      production of the anti-inflammatory cytokine IL-10. These data suggest that
      analysis of antigen-specific IFN-gamma responses could be a useful tool for
      diagnosis of acute Q fever. Moreover, the current model of C. burnetii infection
      could be used to give new insights into immunological factors that predispose to
      development of persistent infection.

PMID- 25618422
TI  - Distribution of serotonin and dopamine in the central nervous system of the
      female mud crab, Scylla olivacea (Herbst).
AB  - In crustaceans serotonin (5-HT) and dopamine (DA) are neurotransmitters that play
      roles in the modulation of numerous physiological functions, including
      reproduction. However, in the mud crab, Scylla olivacea, the distributions of 5
      HT and DA in the CNS have not yet been investigated. The aim of our study was to
      map the distributions of these two neurotransmitters in the central nervous
      system (CNS) of the female of this crab during the late stage of ovarian
      development. We found 5-HT immunoreactivity (-ir) and DA-ir in many parts of the
      CNS, including the eyestalk, brain, and thoracic ganglia. In the eyestalk, 5-HT
      ir was localized in the medulla terminalis (MT), hemi-ellipsoid body (HB), and
      protocerebral tract (PT), whereas DA-ir was present in neuronal cluster 1, the LG
      neuropils, and PT. In the brain, 5-HT-ir and DA-ir were detected in cells and
      fibers of neuronal clusters 6, 7, 8, 9, 10, 11, 14, and 15. In the ventral nerve
      cord, 5-HT-ir was present in neurons of the abdominal ganglia, whereas DA was
      only present in fibers. These spatial distributions of 5-HT and DA suggest that
      they may be involved in the neuromodulation of important physiological functions,
      including ovarian maturation, as shown in other non-crab decapods. 

PMID- 25618423
TI  - Characterization and stress-induced expression analysis of Alfin-like
      transcription factors in Brassica rapa.
AB  - The Alfin-like (AL) transcription factors (TFs) family is involved in many
      developmental processes, including the growth and development of roots, root hair
      elongation, meristem development, etc. However, stress resistance-related
      function and the regulatory mechanism of these TFs have yet to be elucidated.
      This study identified 15 Brassica rapa AL (BrAL) TFs from BRAD database, analyzed
      the sequences and profiled their expression first time in response to Fusarium
      oxysporum f. sp. conglutinans and Pectobacterium carotovorum subsp. carotovorum
      in fection, cold, salt and drought stresses in B. rapa. Structural and
      phylogenetic analyses of 15 BrAL TFs revealed four distinct groups (groups I-IV)
      with AL TFs of Arabidopsis thaliana. In the expression analyses, ten BrAL TFs
      showed responsive expression after F. oxysporum f. sp. conglutinans infection,
      while all BrAL TFs showed responses under cold, salt and drought stresses in B.
      rapa. Interestingly, ten BrAL TFs showed responses to both biotic and abiotic
      stress factors tested here. The differentially expressed BrAL TFs thus represent
      potential resources for molecular breeding of Brassica crops resistant against
      abiotic and biotic stresses. Our findings will also help to elucidate the complex
      regulatory mechanism of AL TFs in stress resistance and provide a foundation for
      further functional genomics studies and applications.

PMID- 25618424
TI  - Immunosuppressive therapy and cancer risk in ocular inflammation patients: fresh
      evidence and more questions.

PMID- 25618425
TI  - Optical coherence tomography, fluorescein angiography, and the management of
      neovascular age-related macular degeneration.

PMID- 25618426
TI  - Oculoplastic and orbital surgery: millennia in the making.

PMID- 25618427
TI  - Author reply: To PMID 24326107.

PMID- 25618428
TI  - Re: Rudnisky et al.: antibiotic choice for the prophylaxis of post-cataract
      extraction endophthalmitis (Ophthalmology 2014;121:835-41).

PMID- 25618429
TI  - Re: Mwanza et al.: diagnostic performance of optical coherence tomography
      ganglion cell-inner plexiform layer thickness measurements in early glaucoma
      (Ophthalmology 2014;121:849-54).

PMID- 25618430
TI  - Author reply: To PMID 24393348.

PMID- 25618431
TI  - Author reply: To PMID 24869467.

PMID- 25618432
TI  - Re: Charlson et al.: nocturnal systemic hypotension increases the risk of
      glaucoma progression (Ophthalmology 2014;121:2004-10).

PMID- 25618433
TI  - Re: Kessel et al.: post-cataract prevention of inflammation and macular edema by
      steroid and nonsteroidal anti-inflammatory eye drops: a systematic review
      (Ophthalmology 2014;121:1915-24).

PMID- 25618434
TI  - Author reply: To PMID 24935281.

PMID- 25618435
TI  - Proteolytic activity and cytokine up-regulation by non-albicans Candida albicans.
AB  - Mouth is an important source of infections and oral infections such as Candida
      infections increase the risk of mortality. Our purpose was to investigate
      differences in proteolytic activity of non-albicans Candida albicans (non
      albicans Candida) between clinical isolates and laboratory samples. The second
      aim was to assess the concentration of pro- and anti-inflammatory cytokine levels
      IL-1beta, IL-10, and TNF-alpha in saliva of patients with the non-albicans
      Candida and Candida-negative saliva samples. Clinical yeast samples from our
      laboratory were used for analyses. Candida strains were grown in YPG at 37 
      degrees C for 24 h in water bath with shaking. The activity of Candida
      proteinases of cell and cell-free fractions were analyzed by MDPF-gelatin
      zymography. The levels of IL-1beta, IL-10, and TNF-alpha were measured from
      saliva with ELISA. The study showed differences in the proteolytic activity among
      the non-albicans Candida strains. C. tropicalis had higher proteolytic activity
      when compared to the other strains. Significant difference was found in salivary
      IL-1beta levels between the non-albicans Candida and control strains (P < 0.002).
      The present findings showed differences in proteolytic activity among the non
      albicans Candida strains. The increased IL-1beta concentration may be one of the
      host response components associated with non-albicans Candida infection. 

PMID- 25618436
TI  - The changing epidemiology of bacteraemic osteoarticular infections in the early
      21st century.
AB  - Osteoarticular infections (OAI), which are often associated with bacteraemia,
      seem to be increasing. We studied all patients with bacteraemia and concomitant
      OAI: septic arthritis (SA), vertebral osteomyelitis (VOM) or peripheral
      osteomyelitis (POM), which were seen at our institution (1985-2011). Data were
      extracted from a prospective protocol of bacteraemia cases recorded. Trends in
      main findings were considered in five periods. Major antibiotic resistance
      patterns were studied. A total of 601 cases of bacteraemic OAI, accounting for
      1.8% of total bactaeremias, were studied: SA (48%), VOM (40%) and POM (17%). When
      comparing the 1985-91 and 2007-11 periods, the incidence of bacteraemic OAI
      increased from 2.34 to 5.78 episodes/100 000 inhabitants per year (p <0.001); and
      nosocomial and healthcare-related cases increased from 18% to 30% (p <0.001) and
      from 10% to 25% (p <0.001), respectively. Also, there was an increase of age
      (median, from 49 to 65 years, p <0.001), patients with comorbidities (23% to 59%,
      p <0.001), and device-related OAI (7% to 28%, p <0.001). Patterns of OAI were
      changing over time. Compared with younger patients, older adults (>= 65 years)
      had more VOM, prosthetic-joint infections and enterococcal OAI. The percentage of
      OAI caused by methicillin-susceptible Staphylococcus aureus decreased, while
      those caused by methicillin-resistant S. aureus, streptococci, enterococci, and
      Gram-negative bacilli increased. There was a link between certain microorganisms
      with specific OAI and age of patients. Over the past three decades, bacteraemic
      OAI increased in association with aging and use of orthopaedic devices.
      Nosocomial and healthcare-related OAI increased, with a rise in multidrug
      resistant bacteria. These trends should be considered when planning diagnostic
      and therapeutic guidelines for OAI. 

PMID- 25618437
TI  - Self-immolation and its adverse life-events risk factors: results from an Iranian
      population.
AB  - BACKGROUND: Despite considerable loss of life by deliberate self-burning in low
      and middle-income countries, few scholars have examined psychiatric factors such
      as adverse life events that may be related to self-immolation. METHODS: This case
      control study investigated adverse life-events as risk factors for self
      immolation patients admitted to a burn center serving the western region of Iran.
      Variables investigated included the following adverse life-events: unplanned
      pregnancy, infertility, homelessness, financial hardship, problems with friends,
      intimate relationship break-up , school or university failure, anxiety about
      school/university performance, problems at work, personal history of suicide
      attempts, family history of suicide attempts, individual history of mental
      disorders, and malignant disease. RESULTS: Financial hardship (OR=3.35, 95%
      CI=1.19-9.90), intimate relationship break-up (OR=5.45, 95% CI=1.20-11.99), and
      personal history of suicide attempts (OR=7.00, 95% CI=1.38-35.48) were associated
      with increased risk of self-immolation. CONCLUSIONS: This study suggests that
      financial hardship, intimate relationship break-ups, and personal history of
      suicide attempts are risk factors for self-immolation. Other variables studied
      did not play a role as individually protective or risk factors for self
      immolation. Further study is needed to substantiate findings of this study and
      direct research toward tailoring culturally sensitive, empirically-supported
      interventions for prevention of self-immolation.

PMID- 25618438
TI  - Acute kidney injury.
AB  - Acute kidney injury is a frequent and serious complication in hospitalized
      patients. Mortality rates have not substantially been decreased during the last
      20 years. In most patients AKI results from transient renal hypoperfusion or
      ischemia. The consequences include tubular cell dysfunction/damage, inflammation
      of the organ, and post-ischemic microvasculopathy. The two latter events
      perpetuate kidney damage in AKI. Clinical manifestations result from diminished
      excretion of water, electrolytes, and endogenous / exogenous waste products.
      Patients are endangered by cardiovascular complications such as hypertension,
      heart failure, and arrhythmia. In addition, the whole organism may be affected by
      systemic toxification (uremia). The diagnostic approach in AKI involves several
      steps with renal biopsy inevitable in some patients. The current therapy focuses
      on preventing further kidney damage and on treatment of complications. Different
      pharmacological strategies have failed to significantly improve prognosis in AKI.
      If dialysis treatment becomes mandatory, intermittent and continuous renal
      replacement therapies are equally effective. Thus, new therapies are urgently
      needed in order to reduce short- and long-term outcome in AKI. In this respect,
      stem cell-based regimens may offer promising perspectives.

PMID- 25618440
TI  - A comprehensive ap-proach to reduce sickness absenteeism.

PMID- 25618439
TI  - The potential role of regenerative medicine in the man-agement of traumatic
      patients.
AB  - Traumatic injury represents the most common cause of death in ages 1 to 44 years
      and asignificant proportion of patients treated in hospital emergency wards each
      year. Unfortunately, for patients who survive their injuries, survival is not
      equal to complete recovery. Many traumatic injuries are difficult to treat with
      conventional therapy and result in permanent disability. In such situations,
      regenerative medicine has the potential to play an important role in recovery of
      function. Regenerative medicine is a field that seeks to maintain or restore
      function with the development of biological substitutes for diseased or damaged
      tissues. Several regenerative approaches are currently under investigation, with
      a few achieving clinical application. For example, engineered skin has gained FDA
      approval, and more than 20 tissue engineered skin substitutes are now
      commercially available. Other organ systems with promising animal models and
      small human series include the central and peripheral nervous systems, the
      musculoskeletal system, the respiratory and genitourinary tracts, and others.
      This paper will be a clinically oriented review of the regenerative approaches
      currently under investigation of special interest to those caring for traumatic
      patients.

PMID- 25618441
TI  - TCDD-induced activation of aryl hydrocarbon receptor regulates the skin stem cell
      population.
AB  - The environmental toxin 2,3,7,8 tetrachlorodibenzo p-dioxin (TCDD) plays an
      important role in the development of chloracne. Chloracne is characterized by
      hyperkeratosis of the interfollicular squamous epithelium and metaplasia of
      sebaceous glands. Dysregulation of keratinocyte terminal differentiation leading
      to accelerated formation of the cornified envelope as a result of TCDD-mediated
      aryl hydrocarbon receptor (AHR) activation has been implicated as one of the
      molecular pathogenic mechanisms contributing to the development of chloracne. In
      addition, chloracne is characterized by altered skin stem cell characteristics,
      and it has been speculated that the phenotype of chloracne closely matches that
      of c-Myc overexpressing transgenic mice. Therefore, we sought to determine
      whether TCDD plays a role in regulation of the skin stem cell population. We have
      proposed in this report that TCDD may directly or indirectly (via AHR receptor
      cross-talk) upregulate c-Myc via epidermal growth factor receptor-extracellular
      signal regulated kinase (EGFR-ERK) axis stimulation, which may correspond with an
      increase in human epidermal stem cell activation and differentiation of EPSCs
      into keratinocytes, with eventual depletion of the epidermal stem cell
      compartment of the skin. Thus, TCDD may cause increased epidermal stem cell
      turnover during chloracne. 

PMID- 25618442
TI  - MIR210 as a potential molecular target to block invasion and metastasis of
      gastric cancer.
AB  - The epithelial-mesenchymal transition (EMT) is a process driving invasion,
      recurrence, and metastasis of gastric cancer, and EMT is triggered by specific
      physiological factors that arise during tumorigenesis, such as hypoxia.
      Identifying the molecular mechanisms underlying EMT will potentially yield
      insight into the pathways fueling cancer recurrence and metastasis and thus, lead
      to novel molecular targets that will improve treatment of the disease. The
      microRNA210 (MIR210) is such a candidate molecule mediating EMT in gastric cancer
      based on a number of observations. First, MIR210 is often highly overexpressed in
      gastric cancer. Second, MIR210 is a hypoxia-specific miRNA, and its expression is
      significantly increased in hypoxic environments where EMT develops. Third, MIR210
      is regulated by hypoxia inducible factor 1alpha (HIF-1alpha), a key transcription
      factor mediating important tumor associated processes such as EMT and
      angiogenesis in response to hypoxia during tumorigenesis. Finally, MIR210 has
      been intriguingly associated with Helicobacterpylori infection, which typically
      develops in an anaerobic environment and is known to have a causal role in the
      development of gastric cancer. Although studies have shown that MIR210 is often
      highly expressed in gastric cancer and associated with specific pathological
      conditions, functional experiments have not yet been performed to determine the
      role of MIR210 and downstream mediators in the development and progression of
      gastric cancer. Here, MIR210 is proposed as a viable molecular target in the
      treatment of gastric cancer, specifically for the inhibition of invasion and
      metastasis. 

PMID- 25618443
TI  - A possible relationship between Takotsubo cardiomyopathy and female sex steroid
      related modulation of functional cerebral asymmetry.
AB  - Takotsubo cardiomyopathy (Tc) is a transient left ventricular apical ballooning
      syndrome, with symptoms and signs of acute myocardial infarction. Tc syndrome,
      which occurs predominantly in postmenopausal women, is characterized by increase
      of sympathetic activity. Studies on the gender-specific differences in sympatho
      vagal regulation and functional cerebral asymmetry (FCA) imply that female
      pattern of dominance is characterized by the left hemisphere, which is believed
      to have parasympathetic predominance, whereas male pattern indicates dominance of
      the right hemisphere, which is believed to have sympathetic predominance.
      Fluctuating levels of female sex steroids are supposed to change FCA, modulating
      transcallosal inter-hemispheric inhibition across the menstrual cycle. The
      findings suggest that FCA is enhanced during the low steroid phase (menstrual
      phase), whereas, during high estrogen and/or progesterone phases (follicular and
      luteal phase) FCA is reduced. This theory is in line with concept of decreased
      magnitude of inter-hemispheric cortical lateralization in premenopausal women
      compared to men and postmenopausal women. Therefore, if postmenopausal women are
      more lateralized for a variety of cerebral functions, they have less balanced
      equilibrium between the right-sided sympathetic and left-sided parasympathetic
      predominance. Decrease of endogenous female sex steroid levels in postmenopausal
      women leads to reduced influence of estrogens to the left hemisphere, which is
      believed to have parasympathetic predominance. If both of these mechanisms result
      in sympatho-vagal imbalance, increasing sympathetic system activity in
      postmenopausal women, it seems reasonable why postmenopausal women became more
      susceptible to sympathetically-mediated syndromes such as Takotsubo
      cardiomyopathy. 

PMID- 25618444
TI  - Enhancement of a solar photo-Fenton reaction with ferric-organic ligands for the
      treatment of acrylic-textile dyeing wastewater.
AB  - Literature describes a kinetic mineralization profile for most of acrylic-textile
      dyeing wastewaters using a photo-Fenton reaction characterized by a slow
      degradation process and high reactants consumption. This work tries to elucidate
      that the slow decay on DOC concentration is associated with the formation of
      stable complexes between Fe(3+) and textile auxiliary products, limiting the
      photoreduction of Fe(3+). This work also evaluates the enhancement of a solar
      photo-Fenton reaction through the use of different ferric-organic ligands applied
      to the treatment of a simulated acrylic-textile dyeing wastewater, as a pre
      oxidation step to enhance its biodegradability. The photo-Fenton reaction was
      negatively affected by two dyeing auxiliary products: i) Sera((r)) Tard A-AS, a
      surfactant mainly composed of alkyl dimethyl benzyl ammonium chloride and ii)
      Sera((r)) Sperse M-IW, a dispersing agent composed of polyglycol solvents. The
      catalytic activity of the organic ligands toward the ferrous-catalysed system
      followed this order: Fe(III)-Oxalate > Fe(III)-Citrate > Fe(III)-EDDS, and all
      were better than the traditional photo-Fenton reaction. Different design
      parameters such as iron concentration, pH, temperature, flow conditions, UV
      irradiance and H2O2 addition strategy and dose were evaluated. The ferrioxalate
      induced photo-Fenton process presented the best results, achieving 87%
      mineralization after 9.3 kJUV L(-1) and allowing to work until near neutral pH
      values. As expected, the biodegradability of the textile wastewater was
      significantly enhanced during the photo-Fenton treatment, achieving a value of
      73%, consuming 32.4 mM of H2O2 and 5.7 kJUV L(-1). 

PMID- 25618445
TI  - Early psychological reactions in parents of children with a life threatening
      illness within a pediatric hospital setting.
AB  - RESEARCH IN CONTEXT: Parents of children with life threatening illness or
      injuries are at elevated risk of distress reactions, involving symptoms of acute
      stress disorder, depression and anxiety. Currently, the impact of child illness
      factors is unclear, and to date research systematically examining the prevalence
      of these psychological reactions across different illness groups with an acute
      life threat is sparse. This is important to explore given that studies show that
      parent functioning impacts on the psychological adjustment and recovery of the
      ill child. WHAT DOES THIS STUDY ADD?: At four weeks following a child's diagnosis
      of a serious illness, 49-54% of parents met DSM-IV criteria for acute stress
      disorder, across a number of illness groups, whereas 15-27% of parents were in
      the moderate/severe range for depression and anxiety, and 25-31% for stress.
      Results from this study demonstrate that rates and severity of these
      psychological reactions in parents of seriously ill children do not vary
      according to illness type. BACKGROUND: A life threatening childhood
      illness/injury can lead to significant distress reactions in parents, with
      independent studies finding such reactions in several different illness groups.
      To date, there is limited research systematically comparing the prevalence of
      adverse parental psychological reactions across different childhood illness
      groups with an acute life threat. This study aimed to investigate the frequency
      and severity of symptoms of acute traumatic stress, depression, anxiety and
      general stress in parents, following admission of their child to hospital for a
      life threatening illness. The study also aimed to explore the relationship
      between these symptoms, and to determine whether they differ according to
      illness/injury. METHODS: Cross-sectional data from a prospective, longitudinal
      study are reported. Participants were 194 parents of 145 children (49 couples),
      admitted to cardiology (n=53), oncology (n=40) and pediatric intensive care units
      (n=52), for serious illnesses/injuries. Parents completed self-report
      questionnaires within four weeks of hospital admission. RESULTS: Rates of acute
      traumatic stress (P=0.262), depression (P=0.525), anxiety (P=0.453) and general
      stress symptoms (P=0.720) in parents were comparable across illness type, with 49
      54% reaching criteria for acute stress disorder, 15-27% having clinical levels of
      depression and anxiety, and 25-31% for general stress. Anxiety was most strongly
      associated with acute traumatic stress (r=0.56), closely followed by stress
      (r=0.52) and depression (r=0.49), with all correlations highly significant
      (P<0.001). CONCLUSIONS: These findings provide evidence that the child's medical
      condition is not associated with parents' experience of clinically significant
      psychological symptoms, and emphasize the importance for health care providers to
      be aware of these potential psychological reactions in parents, regardless of the
      type of illness.

PMID- 25618447
TI  - Comment on: infants of opioid-dependent mothers: neurodevelopment at six months.

PMID- 25618446
TI  - Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to
      Marijuana Cannabinoids and its Long Term Consequences in Offspring.
AB  - Use of marijuana during pregnancy is fairly commonplace and can be expected
      increase in frequency as more states legalize its recreational use. The
      cannabinoids present in marijuana have been shown to be immunosuppressive, yet
      the effect of prenatal exposure to cannabinoids on the immune system of the
      developing fetus, its long term consequences during adult stage of life, and
      transgenerational effects have not been well characterized. Confounding factors
      such as co-existing drug use make the impact of cannabis use on progeny
      inherently difficult to study in a human population. Data from various animal
      models suggests that in utero exposure to cannabinoids results in profound T cell
      dysfunction and a greatly reduced immune response to viral antigens. Furthermore,
      evidence from animal studies indicates that the immunosuppressive effects of
      cannabinoids can be mediated through epigenetic mechanisms such as altered
      microRNA, DNA methylation and histone modification profiles. Such studies support
      the hypothesis that that parental or prenatal exposure to cannabis can trigger
      epigenetic changes that could have significant immunological consequences for
      offspring as well as long term transgenerational effects. 

PMID- 25618448
TI  - Copeptin (C-terminal pro arginine-vasopressin) is an independent long-term
      prognostic marker in heart failure with reduced ejection fraction.
AB  - BACKGROUND: The level of copeptin, a stable fragment of pro-arginine-vasopressin
      (AVP), correlates with disease severity. It is an established, short-term
      prognostic marker for patients with heart failure with reduced ejection fraction
      (HFREF). We aimed to examine the association between copeptin and long-term
      mortality. We also studied the clinical usefulness of copeptin as a prognostic
      biomarker by analysing the improvement of net reclassification. METHODS: Copeptin
      concentrations were measured in a cohort of 195 consecutive patients with HFREF.
      Disease severity and clinical parameters were determined at baseline, and all
      cause mortality was recorded after five-year follow-up. RESULTS: One hundred and
      ten patients died during the five-year follow-up (five-year mortality rate:
      0.56). Univariate analysis identified copeptin (HR 2.168 [95% CI 1.740-2.700]) as
      a predictor of mortality. The final, multivariable Cox survival model identified
      a number of independent predictors of death. These included higher NHYA
      functional class, previous MI, at least one hospitalisation for worsening HF
      (within the two years before inclusion into the study), elevated blood urea
      nitrogen, NT-proBNP-, and copeptin levels, as well as increased red blood cell
      distribution width, and decreased GFR. The addition of copeptin alone to the
      baseline predictive model (NT-proBNP only) resulted in a minor (8.21%)
      improvement, whereas the final, multivariable model showed a significant increase
      in net reclassification (10.26%, p=0.015). CONCLUSIONS: These data indicate that
      copeptin is an independent long-term prognostic marker in HFREF, with possible
      clinical relevance for multimarker risk prediction algorithms.

PMID- 25618449
TI  - Age-specific gender differences in long-term recurrence and mortality following
      incident myocardial infarction: a population-based study.
AB  - BACKGROUND: Higher mortality following myocardial infarction (MI) is reported in
      women compared with men with short-term follow-up. Our study aim was to compare
      long-term gender- and age-specific outcomes following incident MI. METHODS: 30
      day survivors of incident MI from 2003-2009 were identified from linked
      administrative data in Western Australia. Outcomes identified were recurrent MI,
      and cardiovascular and all-cause mortality. Follow-up data was available until
      30(th) June 2011. Unadjusted risk out to eight-years was estimated from Kaplan
      Meier survival curves, and multivariate Cox regression models were used to
      estimate relative risk in women compared with men by age group. RESULTS: There
      were 12,420 30-day survivors of incident MI from 2003-2009 (males 71.2%). Women
      had higher levels of comorbidities across all age groups compared with men.
      Unadjusted event risks were higher in women than men overall, underpinned by
      higher risk of recurrent MI in 55-69 year-old women and of cardiovascular
      mortality across all age groups in women. Gender differences were generally
      attenuated after adjustment for demographic factors and comorbidities.
      CONCLUSIONS: This study highlights the elevated risk of cardiovascular events in
      women compared with men with long-term follow-up, and demonstrates the need for
      improved long-term secondary prevention in this patient group.

PMID- 25618450
TI  - Pattern visual evoked potentials for identifying malingering.
AB  - PURPOSE: To investigate the efficacy of pattern visual evoked potentials (VEPs)
      in evaluating objective visual acuity (VA) and discriminating malingerers.
      METHODS: Two hundred and forty-nine eyes of 249 patients aged 20-65 years were
      included. There were 147 eyes with macular diseases (group 1) and 102 eyes with
      optic nerve diseases (group 2). Amplitudes and latencies were analyzed and
      correlated with best-corrected visual acuity by a regression analysis. We found
      the best-correlated mode of pattern VEP, determined the relations, and then
      calculated the pattern VEP-estimated VA (PVEP-VA) of all 249 eyes, another 30
      malingering eyes, 13 eyes with macular diseases, and 17 eyes with optic nerve
      diseases, and used a receiver operating characteristic (ROC) curve to determine a
      cutoff for acceptable variance between PVEP-VA and subjective VA to discriminate
      malingerers. RESULTS: The best correlation was between the amplitude of 50'
      checkerboard size (Amp50') and VA in every group. Significant correlation was
      between Amp50' and VA, where p < 0.0001 in group 1 and p = 0.020 in group 2. A
      logarithmic curve best fitted the correlation in the regression analysis, where y
      = 1.731 - 1.569x (R(2) = 0.611, p < 0.0001) in group 1 and y = 2.413 - 2.169x
      (R(2) = 0.531, p < 0.0001) in group 2 [x: log(Amp50'), y: PVEP-VA (logMAR)]. By
      using the relations and ROC curve, we determined a variance value of 0.4041
      (logMAR) with 100% sensitivity and 94.0% specificity in group 1 and 0.3658 with
      70.6% sensitivity and 50.5% specificity in group 2 to discriminate malingerers.
      CONCLUSIONS: The pattern VEP amplitude of 50' checkerboard size was useful to
      assess VA and can be helpful in discriminating malingering from real disability.

PMID- 25618451
TI  - Radiological evaluation of anterior lumbar fusion using PEEK cages with adjacent
      vertebral autograft in spinal deformity long fusion surgeries.
AB  - PURPOSE: The aim of this study was to evaluate the radiographic characteristics
      of polyetheretherketone (PEEK) cages packed with adjacent vertebral autograft
      material in lumbar anterior lumbar interbody fusion (ALIF) in spinal deformity
      long fusion surgeries. METHODS: This is a retrospective radiographic study. From
      April 2008 to April 2012, 40 patients (5 males and 35 females, mean age 67 +/- 9
      years) with coronal and/or sagittal spine deformities underwent staged corrective
      surgery combined with lumbar ALIF using PEEK cages at the L3-L4, L4-L5 or L5-S1
      segment with posterior long (>= 4 levels) instrumentation. The mean follow-up
      time was 27.5 months (13-49 months). We examined the interbody fusion rate and
      cage subsidence at 3 months postoperatively and final follow-up. Additionally, we
      evaluated the distance of cage migration at final follow-up and the improvement
      in lumbar lordosis. The rate of "collapse" of the adjacent vertebra where the
      autograft was harvested was assessed at the final follow-up. Finally, we examined
      the cage-related postoperative complications in this series. RESULTS: Solid
      interbody fusion was achieved in 96.4 % (81/84) of the levels at the final follow
      up. A mild forward cage migration was observed, and the mean migration distance
      at final follow-up was 0.83 mm in L3/4, 0.36 mm in L4/5 and 0.55 mm in L5/S1.
      There was cage subsidence observed in 8.3 % (7/84) of the levels. In all
      patients, the PEEK cage maintained a significant increase in segmental lordosis
      at all postoperative visits. However, a mild reduction in segmental lordosis
      still occurred with time. The adjacent lumbar vertebral bodies where the
      autografts were harvested appeared to be intact in height radiologically at the
      final follow-up. There were no postoperative complications due to bone harvesting
      or cage insertion. Proximal junctional kyphosis was found in one patient who
      underwent a subsequent revision surgery. CONCLUSIONS: The use of lumbar ALIF with
      PEEK cages and adjacent vertebral autografts in spinal deformity long fusion
      surgeries is an effective and safe procedure. The allograft filler is safe and
      effective in maintaining the shape of harvested vertebrae. Additional long-term
      follow-up studies are needed to further justify its use.

PMID- 25618452
TI  - An evaluation of multimodal spinal cord monitoring in scoliosis surgery: a single
      centre experience of 354 operations.
AB  - PURPOSE: To evaluate the effectiveness of multimodal intraoperative
      neuromonitoring in the early detection of impending spinal cord injury during
      surgery for spinal deformity. METHOD: A retrospective review of prospectively
      collected data in 354 consecutive spinal deformity operations from June 2003 to
      October 2013. Patients were sub-grouped according to demographics, diagnosis and
      operative features. Post-operative neurological deficit was defined as either
      spinal cord, nerve root or transient deficit. RESULTS: Combined monitoring with
      SSEPs and MEPs was possible in 315 cases. The overall incidence of significant
      alerts was 7.1 % and overall permanent neurological deficit was 1.6 %. When
      results were collated, the overall combined sensitivity of multimodal monitoring
      was 100 % with a specificity of 99.3 %. CONCLUSIONS: Multimodal monitoring allows
      early detection of impending neurological deficit that is superior to a single
      monitoring modality. To achieve optimal use of monitoring, continuous
      communication between surgical, anaesthetic and neurophysiology teams are
      required. As a result of our experience we have incorporated in our consent
      procedure the discussion of monitoring and the possibility of needing to abandon
      the procedure, and completing in a staged fashion at a later date. We believe
      multimodal monitoring is the current gold standard for complex spinal deformity
      surgery.

PMID- 25618453
TI  - Assessing the quality of available patient reported outcome measures for
      intermittent claudication: a systematic review using the COSMIN checklist.
AB  - OBJECTIVE: The aim was to critically appraise, compare, and summarize the quality
      of the measurement properties of all available disease specific patient reported
      outcome measures (PROMs) on health related quality of life and functional status
      validated in patients with intermittent claudication (IC). METHODS: A systematic
      search was carried out in Embase and Medline (last search November 18, 2013). The
      quality of the identified studies was assessed per measurement property according
      to the COnsensus-based Standards for the selection of health Measurements
      Instruments (COSMIN) checklist. Data on the measurement properties were extracted
      to determine a level of evidence per measurement property per instrument.
      RESULTS: Forty three studies were found evaluating 10 health related quality of
      life and two functional status PROMs. Evidence for the existence of subscales
      (structural validity) and for internal consistency (interrelatedness of items
      within subscales) for PROMs was generally poor. Evidence for construct validity
      was limited. Accuracy and reproducibility of PROMs were often uncertain, since
      reliability studies were mostly performed in small patient samples.
      Responsiveness, or the ability of PROMs to detect change over time, was hardly
      ever studied. CONCLUSION: The quality of the validation of most disease specific
      PROMs for IC is alarming, hampering all conclusion based on these PROMs.
      Considering the results, the PAD quality of life questionnaire (PADQOL),
      Intermittent claudication questionnaire (ICQ) and the Vascular quality of life
      questionnaire (VascuQol) might be appropriate PROMs for health related quality of
      life, while the Walking impairment questionnaire (WIQ) and Estimate ambulation
      capacity by history questionnaire (EACH-Q) appear suitable PROMs for functional
      status. However, all PROMs require further validation studies to fill the gaps in
      their measurement properties. The shortcomings highlighted in this review should
      be taken into account when interpreting PROM results.

PMID- 25618454
TI  - Stenosing esophageal carcinoma diagnosed by endobronchial ultrasound.

PMID- 25618455
TI  - Variability in home mechanical ventilation prescription.
AB  - INTRODUCTION: Few studies have analyzed the prevalence and accessibility of home
      mechanical ventilation (HMV). The aim of this study was to characterize the
      prevalence of HMV and variability in prescriptions from administrative data.
      METHODS: Prescribing rates of HMV in the 37 healthcare sectors of the Catalan
      Health Service were compared from billing data from 2008 to 2011. Crude
      accumulated activity rates (per 100,000 population) were calculated using
      systematic component of variation (SCV) and empirical Bayes (EB) methods.
      Standardized activity ratios (SAR) were described using a map of healthcare
      sectors. RESULTS: A crude rate of 23 HMV prescriptions per 100,000 population was
      observed. Rates increase with age and have increased by 39%. Statistics measuring
      variation not due to chance show a high variation in women (CSV=0.20 and EB=0.30)
      and in men (CSV=0.21 and EB=0.40), and were constant over time. In a multilevel
      Poisson model, hospitals with a chest unit were associated with a greater number
      of cases (beta=0.68, P<.0001). CONCLUSIONS: High variability in prescribing HMV
      can be explained, in part, by the attitude of professionals towards treatment and
      accessibility to specialist centers with a chest unit. Analysis of administrative
      data and variability mapping help identify unexplained variations and, in the
      absence of systematic records, are a feasible way of tracking treatment.

PMID- 25618456
TI  - Use of computational fluid dynamics in respiratory medicine.
AB  - Computational Fluid Dynamics (CFD) is a computer-based tool for simulating fluid
      movement. The main advantages of CFD over other fluid mechanics studies include:
      substantial savings in time and cost, the analysis of systems or conditions that
      are very difficult to simulate experimentally (as is the case of the airways),
      and a practically unlimited level of detail. We used the Ansys-Fluent CFD program
      to develop a conducting airway model to simulate different inspiratory flow rates
      and the deposition of inhaled particles of varying diameters, obtaining results
      consistent with those reported in the literature using other procedures. We hope
      this approach will enable clinicians to further individualize the treatment of
      different respiratory diseases. 

PMID- 25618457
TI  - Collateral Resistance and Sensitivity Modulate Evolution of High-Level Resistance
      to Drug Combination Treatment in Staphylococcus aureus.
AB  - As drug-resistant pathogens continue to emerge, combination therapy will
      increasingly be relied upon to treat infections and to help combat further
      development of multidrug resistance. At present a dichotomy exists between
      clinical practice, which favors therapeutically synergistic combinations, and the
      scientific model emerging from in vitro experimental work, which maintains that
      this interaction provides greater selective pressure toward resistance
      development than other interaction types. We sought to extend the current
      paradigm, based on work below or near minimum inhibitory concentration levels, to
      reflect drug concentrations more likely to be encountered during treatment. We
      performed a series of adaptive evolution experiments using Staphylococcus aureus.
      Interestingly, no relationship between drug interaction type and resistance
      evolution was found as resistance increased significantly beyond wild-type
      levels. All drug combinations, irrespective of interaction types, effectively
      limited resistance evolution compared with monotreatment. Cross-resistance and
      collateral sensitivity were found to be important factors in the extent of
      resistance evolution toward a combination. Comparative genomic analyses revealed
      that resistance to drug combinations was mediated largely by mutations in the
      same genes as single-drug-evolved lineages highlighting the importance of the
      component drugs in determining the rate of resistance evolution. Results of this
      work suggest that the mechanisms of resistance to constituent drugs should be the
      focus of future resistance evolution work. 

PMID- 25618458
TI  - Assortative mating drives linkage disequilibrium between sperm and egg
      recognition protein loci in the sea urchin Strongylocentrotus purpuratus.
AB  - Sperm and eggs have interacting proteins on their surfaces that influence their
      compatibility during fertilization. These proteins are often polymorphic within
      species, producing variation in gamete affinities. We first demonstrate the
      fitness consequences of various sperm bindin protein (Bindin) variants in the sea
      urchin Strongylocentrotus purpuratus, and assortative mating between males and
      females based on their sperm Bindin genotype. This empirical finding of
      assortative mating based on sperm Bindin genotype could arise by linkage
      disequilibrium (LD) between interacting sperm and egg recognition loci. We then
      examine sequence variation in eight exons of the sea urchin egg receptor for
      sperm Bindin (EBR1). We find little evidence of LD among the eight exons of EBR1,
      yet strong evidence for LD between sperm Bindin and EBR1 overall, and varying
      degrees of LD between sperm Bindin among the eight exons. We reject the alternate
      hypotheses of LD driven by shared evolutionary histories, population structure,
      or close physical linkage between these interacting loci on the genome. The most
      parsimonious explanation for this pattern of LD is that it represents selection
      driven by assortative mating based on interactions among these sperm and egg
      loci. These findings indicate the importance of ongoing sexual selection in the
      maintenance of protein polymorphisms and LD, and more generally highlight how LD
      can be used as an indication of current mate choice, as opposed to historic
      selection. 

PMID- 25618459
TI  - [Ecthyma gangrenosum associated with infection involving a methicillin-sensitive,
      Panton-Valentine-negative strain of Staphylococcus aureus].
AB  - BACKGROUND: Ecthyma gangrenosum (EG) is an anatomoclinical syndrome commonly
      associated with Pseudomonas aeruginosa cutaneous infection. Other microorganisms
      have also been incriminated on occasion, with other viral, fungal and bacterial
      agents potentially causing EG. In this report, we present an extremely rare case
      of an EG caused by methicillin-sensitive Staphylococcus aureus (MSSA) infection.
      This case, highly characteristic of EG both clinically and histologically, calls
      into question the physiopathological mechanisms of the disease and provides a
      reminder that it may be caused by a variety of organisms. PATIENTS AND METHODS: A
      62-year-old woman, followed for HIV seropositivity at the AIDS stage, developed a
      painful purpuric skin rash evolving towards necrotic nodules characteristic of
      ecthyma gangrenosum. Skin biopsy confirmed the diagnosis of EG due to methicillin
      sensitive S. aureus (MSSA) infection without toxins or bacteraemia. DISCUSSION:
      To the best of our knowledge, this is the first case in the literature in which
      MSSA is reported as the underlying cause of such lesions.

PMID- 25618460
TI  - Language of perfectionistic parents predicting child anxiety diagnostic status.
AB  - Previous research has identified parental perfectionism as a risk factor for
      child anxiety. Yet few studies investigated why parental perfectionism may play
      such a role. Based on research suggesting parental verbal information and
      language use are associated with increased child fear beliefs and anxiety, the
      current study investigated the linguistic style of perfectionistic mothers and
      its relation to child anxiety. Participants were 71 mother-child dyads. Children
      were 3-12 years old, 57.7% female, and 30 were diagnosed with an anxiety
      disorder. Analyses showed that parental perfectionism was associated with
      increased second person pronouns, decreased adverbs, negative emotion words, and
      anger words. Second person pronouns and negative emotion words predicted child
      anxiety diagnostic status and mediated the relation between maternal
      perfectionism and child anxiety. These findings suggest that parental
      perfectionism may be associated with a specific language style that is related to
      child anxiety. Implications and future directions are discussed. 

PMID- 25618461
TI  - Fatal aluminum phosphide poisonings in Tirana (Albania), 2009 - 2013.
AB  - BACKGROUND: Acute poisonings particularly through pesticides have become a major
      public health concern in Albania during the last decade. FINDINGS: The number of
      fatalities due to aluminum phosphide intoxications was more than doubled during a
      five year-period from 2009 to 2013, and a cluster of suicides perpetrated with
      Phostoxin was registered. Several factors are accountable for such a phenomenon,
      including the fact that aluminum phosphide agents are freely available in the
      Albanian market, their price is extremely low and they are sold without any legal
      restriction. The mass media unfortunately warranted an emulating effect to
      dramatic intoxications, which gained by such means the notoriety of a secure
      lethal weapon. CONCLUSIONS: Our experience with more than three hundred
      intoxications with aluminum phosphide agents in the last five years, showed that
      a considerable delay from the moment of exposure (mainly through ingestion) to
      specialized medical help seeking, created a considerable obstacle for a
      successful treatment of cases, and eventually for the survival of patients. The
      lack of a specific antidote adds further challenges to all these exposures. The
      need for public health policies aiming at prevention, awareness, and possibly the
      substitution of Phostoxin or other aluminum phosphide pesticides with less
      dangerous agents is formulated.

PMID- 25618462
TI  - Rapid fluorescence spectroscopic characterization of salivary DNA of normal
      subjects and OSCC patients using ethidium bromide.
AB  - Recently, deoxyribonucleic acid (DNA) based biomarker(s) detection has been
      employed for cancer diagnosis. Earlier reports have suggested the presence of
      more DNA in the saliva of oral squamous cell carcinoma (OSCC) than normal by
      electrophoresis technique. Based on these, steady state and excited state
      kinetics of salivary DNA has been performed with 27 normal subjects and 67 OSCC
      patients saliva using ethidium bromide as a probe to look for the possibility in
      discrimination between them. On statistical analysis the sensitivity and
      specificity of 88.9 and 94.0 % has been achieved from the fluorescence emission
      spectra and 88.9 and 92.5 % with that of fluorescence excitation.

PMID- 25618463
TI  - Structural and photophysical properties of (2E)-3-[4-(dimethylamino) phenyl]-1
      (naphthalen-1-yl) prop-2-en-1-one (DPNP) in different media.
AB  - The spectral and photophysical properties of a new chalcone derivative (2E)-3-[4
      (dimethylamino) phenyl]-1-(naphthalen-1-yl) prop-2-en-1-one (DPNP) containing
      donor-acceptor group has been synthesized and characterized on the basis of the
      spectral (IR, (1)HNMR & (13)C NMR) and X- ray crystallographic data. The effect
      of solvents on photophysical parameters such as singlet absorption, molar
      absorptivity, oscillator strength, dipole moment, fluorescence spectra, and
      fluorescence quantum yield of DPNP have been investigated comprehensively.
      Significant red shift was observed in the emission spectrum of DPNP compared to
      the absorption spectrum upon increasing the solvent polarity, indicating a higher
      dipole moment in the excited state than in the ground state. The difference
      between the excited and ground state dipole moments (DeltaMU) were obtained from
      Lippert-Mataga and Reichardts correlations by means of solvatochromic shift
      method. The effects of medium acidity on the electronic absorption and emission
      spectra of DPNP were studied. The interaction of DPNP with colloidal silver
      nanoparticles (AgNPs) was also studied in ethanol and ethylene glycol using
      steady state fluorescence quenching measurements. The fluorescence quenching data
      reveal that dynamic quenching and energy transfer play a major role in the
      fluorescence quenching of DPNP by Ag NPs. 

PMID- 25618464
TI  - In vivo analysis of acromioclavicular joint motion after hook plate fixation
      using three-dimensional computed tomography.
AB  - BACKGROUND: The clavicle hook plate can be used to treat acromioclavicular and
      coracoclavicular ligament injury or distal clavicular fracture with comminution.
      However, the hook plate can induce subacromial impingement, resulting in
      discomfort from the hardware. METHODS: Our inclusion criteria were (1) men and
      women aged older than 20 years and (2) the presence of comminuted distal
      clavicular fractures (Neer type IIB) fixed with a hook plate (Synthes, Oberdorf,
      Switzerland). Three-dimensional computed tomography was obtained before removal
      of the hook plate. Seven patients were enrolled prospectively. The mean age was
      42 years (range, 24-60 years). Zero degree images and abduction images were
      obtained. The sagittal cut surface was obtained 5 mm medial from the distal
      clavicle. The equator of the cut surface of the clavicle was compared with the
      full abduction model to analyze rotation. The center of the cut surface of the
      clavicle was compared with the full abduction model to analyze translation.
      RESULTS: The average difference in rotation of the distal clavicle between both
      shoulders was 16 degrees  (range, 3 degrees -22 degrees ; P = .001). The mean
      difference in anterior translation of the distal clavicle was 2.2 mm (range, -0.7
      to 5.6 mm; P = .030). CONCLUSION: Hook plate fixation at the acromioclavicular
      joint causes decreased internal rotation and increased anterior translation of
      the distal clavicle with respect to the medial acromion, indicating that the
      scapula relative to the thorax has decreased posterior tilting and increased
      external rotation in shoulders fixed using a hook plate.

PMID- 25618465
TI  - Posterior augmented glenoid designs preserve more bone in biconcave glenoids.
AB  - BACKGROUND AND HYPOTHESIS: Total shoulder arthroplasty is recommended treatment
      for severe osteoarthritis of the glenohumeral joint, which often results in
      excessive posterior wear. Two recent glenoid components with posterior augments
      have been designed to correct excessive posterior wear and retroversion. Our
      primary hypothesis was that posterior augmented glenoid designs require less bone
      removal than a standard glenoid design. METHODS: Ten arthritic scapulae
      classified as Walch B2 glenoids were virtually implanted with standard, stepped,
      and wedged components. The volume of surgical bone removal, the maximum reaming
      depth, and the portion of the implant surface in contact with cancellous vs.
      cortical bone were calculated for each implant. RESULTS: The neoglenoid made up
      an average of 65% +/- 12% of the glenoid width. Mean surgical bone volume removed
      was least for the wedged (2857 +/- 1618 mm(3)) compared with the stepped (4307 +/
      1485 mm(3); P < .001) and standard (5385 +/- 2348 mm(3); P < .001) designs.
      Maximum bone depth removed for the wedged (4.2 +/- 2.0 mm) was less than for the
      stepped (7.6 +/- 1.2 mm; P < .001) and standard (9.9 +/- 3.2 mm; P < .001). The
      mean percentage of the implant's back surface supported by cancellous bone was
      18.2% for the standard, 8.8% for the stepped (P = .02), and 4.3% for the wedged
      (P = .01). DISCUSSION: Both augmented components corrected glenoid version to
      neutral and required less bone removal, required less reaming depth, and were
      supported by more cortical bone than in the standard implant. The least amount of
      bone removed was with the wedged design.

PMID- 25618466
TI  - An investigation of attributional style, theory of mind and executive functioning
      in acute paranoia and remission.
AB  - This study assessed associations between attributional style and ToM measures in
      patients with paranoid symptoms and non-clinical controls, as well associations
      between these aspects of social cognition and executive skills. Using a
      longitudinal design, we further assessed performance on measures following the
      remission of paranoid symptoms. Patients and controls completed the Internal
      Personal and Situational Attributions Questionnaire (IPSAQ), ToM tasks, the
      Stroop, the modified Wisconsin Card Sorting Test (WCST) and a measure of
      premorbid IQ at time one. Following the remission of paranoid symptoms, the
      patient group repeated the assessment process. Patients had a higher
      personalising bias for negative events and impairments in second order false
      belief and executive skills compared to control participants. Personalising bias
      for negative events was associated with poorer IQ, a tendency to make
      perseverative errors, a poorer performance on the second order false belief task
      and more severe symptoms. Personalising bias for negative events, performance on
      the second order false belief task or the tendency to make perseverative errors
      did not significantly change following symptom remission. The findings increase
      understanding of the mechanisms that potentially underpin the development and
      maintenance of paranoia. Specifically targeting personalising attributions for
      negative events in remitted patients may be an important goal of psychological
      therapy. 

PMID- 25618467
TI  - The impact of neuropsychological functioning and coping style on perceived stress
      in individuals with first-episode psychosis and healthy controls.
AB  - Stress is implicated in the development and course of psychotic illness, but the
      factors that influence stress levels are not well understood. The aim of this
      study was to examine the impact of neuropsychological functioning and coping
      styles on perceived stress in people with first-episode psychosis (FEP) and
      healthy controls (HC). Thirty-four minimally treated FEP patients from the Early
      Psychosis Prevention and Intervention Centre, Melbourne, Australia, and 26 HC
      participants from a similar demographic area participated in the study.
      Participants completed a comprehensive neuropsychological test battery as well as
      the Coping Inventory for Stressful Situations (task-, emotion- and avoidance
      focussed coping styles) and Perceived Stress Scale (PSS). Linear regressions were
      used to determine the contribution of neuropsychological functioning and coping
      style to perceived stress in the two groups. In the FEP group, higher levels of
      emotion-focussed and lower levels of task-focussed coping were associated with
      elevated stress. Higher premorbid IQ and working memory were also associated with
      higher subjective stress. In the HC group, higher levels of emotion-focussed
      coping, and contrary to the FEP group, lower premorbid IQ, working memory and
      executive functioning, were associated with increased stress. Lower intellectual
      functioning may provide some protection against perceived stress in FEP. 

PMID- 25618468
TI  - Depression status as a predictor of quit success in a real-world effectiveness
      study of nicotine replacement therapy.
AB  - To provide population-level evidence of the role of current depression on smoking
      cessation treatment success, we conducted a secondary analysis of data obtained
      from a large cessation study conducted in over 13,000 smokers. On the basis of
      self-reported history of depression diagnoses at baseline, participants were
      divided into four mutually exclusive groups: current/recent depression, recurrent
      depression, past depression and no depression history. Cessation outcomes were
      compared among the four groups at 6-month follow-up. Of the 6261 individuals who
      were consented and attempted to be contacted for follow-up, 4648 (74.2%) had no
      diagnostic history of depression, 591 (9.4%) had a past history of depression,
      759 (12.1%) had a current/recent depression diagnoses, and 263 (4.2%) had
      recurrent depression (both current and history). Those with recurrent depression
      were significantly less likely to quit smoking compared to those with no history
      of depression. In unadjusted analyses, recurrent depression was associated with
      significantly lower odds of quitting compared to those with either no history or
      a past history of depression. Current/recent depression was also associated with
      poorer quit outcomes compared to those with no history of depression. Depressed
      smokers may benefit from more individualized, in-person approaches to smoking
      cessation. 

PMID- 25618469
TI  - Psychiatrist attitudes towards pharmacogenetic testing, direct-to-consumer
      genetic testing, and integrating genetic counseling into psychiatric patient
      care.
AB  - Psychiatric treatment has not historically included genetic counseling or genetic
      testing. It has been shown that psychiatric patients and their families benefit
      from genetic counseling and pharmacogenetic testing for pharmacological
      treatment. To date, no study has investigated psychiatrists' attitudes towards
      incorporating pharmacogenetic testing and genetic counseling into patient
      treatment. This study employed a five item survey to solicit the opinions of
      psychiatrists on the benefit of pharmacogenetic data, direct to consumer (DTC)
      genetic testing, and genetic counseling. A total of 113 psychiatrists responded
      to the surveys. The vast majority (94.6%) indicated that genetic data would be
      useful in making pharmaceutical decisions, and 86% felt that pharmacogenetic
      testing would become standard of care. Attitudes were split towards the benefit
      of direct to consumer genetic testing; 55.8% of respondents would refer a patient
      for DTC genetic testing that might help with treatment decisions. The majority
      (72.6%) believed that it would be beneficial to include genetic counselors in
      psychiatric patient care. The results of our study suggest there is potential for
      collaboration between psychiatrists and genetic counselors to enhance patient
      care.

PMID- 25618470
TI  - The Body Image Psychological Inflexibility Scale: development and psychometric
      properties.
AB  - Body image disturbance and body dysmorphic disorder (BDD) have been researched
      from a variety of psychological approaches. Psychological inflexibility, or
      avoidance of one's own cognitive and affective states at a cost to personal
      values, may be a useful construct to understand these problems. In an effort to
      clarify the role of psychological inflexibility in body image disturbance and
      BDD, a measure was created based on the principles of Acceptance and Commitment
      Therapy (ACT). The scale was developed by generating new items to represent the
      construct and revising items from an existing scale measuring aspects of body
      image psychological inflexibility. The study was conducted with an ethnically
      diverse undergraduate population using three samples during the validation
      process. Participants completed multiple assessments to determine the validity of
      the measure and were interviewed for BDD. The 16-item scale has internal
      consistency (alpha = 0.93), a single factor solution, convergent validity, and
      test re-test reliability (r = 0.90). Data demonstrate a relationship between
      psychological inflexibility and body image disturbance indicating empirical
      support for an ACT conceptualization of body image problems and the use of this
      measure for body image disturbance and BDD.

PMID- 25618471
TI  - Higher total cholesterol level is associated with suicidal ideation in first
      episode schizophrenia females.
AB  - There are inconsistent reports showing that the relationship between total
      cholesterol (TC) level and suicidality might be gender-specific. We compared 30
      first-episode schizophrenia (FES) patients reporting suicidal ideation based on
      the Operational Criteria for Psychotic Illness (OPCRIT) checklist with 70 FES
      patients, who have never experienced suicidal ideation. After controlling for
      potential confounders, higher TC was associated with suicidal ideation only in
      FES females. Future studies should disentangle biological underpinnings of this
      gender-specific association. 

PMID- 25618472
TI  - Portuguese version of the PTSD Checklist-Military Version (PCL-M)-I: Confirmatory
      Factor Analysis and reliability.
AB  - The PTSD Checklist-Military Version (PCL-M) is a brief self-report instrument
      widely used to assess Post-traumatic Stress Disorder (PTSD) symptomatology in war
      Veterans, according to DSM-IV. This study sought out to explore the factor
      structure and reliability of the Portuguese version of the PCL-M. A sample of 660
      Portuguese Colonial War Veterans completed the PCL-M. Several Confirmatory Factor
      Analyses were conducted to test different structures for PCL-M PTSD symptoms.
      Although the respecified first-order four-factor model based on King et al.'s
      model showed the best fit to the data, the respecified first and second-order
      models based on the DSM-IV symptom clusters also presented an acceptable fit. In
      addition, the PCL-M showed adequate reliability. The Portuguese version of the
      PCL-M is thus a valid and reliable measure to assess the severity of PTSD
      symptoms as described in DSM-IV. Its use with Portuguese Colonial War Veterans
      may ease screening of possible PTSD cases, promote more suitable treatment
      planning, and enable monitoring of therapeutic outcomes.

PMID- 25618473
TI  - The impact of tics, obsessive-compulsive symptoms, and impulsivity on global
      functioning in Tourette syndrome.
AB  - This study investigated the relationships between tics, obsessive-compulsive
      symptoms (OCS), and impulsivity, and their effects on global functioning in
      Japanese patients with Tourette syndrome (TS), using the dimensional approach for
      OCS. Fifty-three TS patients were assessed using the Yale Global Tic Severity
      Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Impulsivity
      Rating Scale, and the Global Assessment of Functioning Scale. Although tic
      severity scores were significantly and positively correlated with OCS severity
      scores, impulsivity severity scores were not significantly correlated with
      either. The global functioning score was significantly and negatively correlated
      with tic and OCS severity scores. Of the 6 dimensional OCS scores, only
      aggression scores had a significant negative correlation with global functioning
      scores. A stepwise multiple regression analysis showed that only OCS severity
      scores were significantly associated with global functioning scores. Despite a
      moderate correlation between tic severity and OCS severity, the impact of OCS on
      global functioning was greater than that of tics. Of the OCS dimensions, only
      aggression had a significant impact on global functioning. Our findings suggest
      that it is important to examine OCS using a dimensional approach when analyzing
      global functioning in TS patients. 

PMID- 25618474
TI  - Effects of sub-clinical psychosis and cognitive insight on psychological well
      being: a structural equation model.
AB  - Psychological well-being has been widely researched along the psychosis spectrum,
      and increased psychotic symptoms are generally associated with worse well-being.
      Additionally, the construct of insight has been extensively studied in
      schizophrenia. While having greater insight has many benefits for those with
      schizophrenia, a paradox exists in which greater insight is also associated with
      poorer psychological well-being. However, it is unclear whether the link between
      insight and poor well-being occurs only once serious psychopathology has been
      established, or whether this is a more universal process seen even at lower
      levels on the psychosis spectrum. We used a structural modeling approach in an
      ethnically diverse, non-clinical sample of 420 undergraduates to evaluate the
      association between sub-clinical psychosis, cognitive insight and psychological
      well-being. As hypothesized, results indicated that sub-clinical psychotic
      symptoms were negatively associated with psychological well-being. The insight
      paradox was also substantiated, as greater cognitive insight was associated with
      worse psychological well-being. However, cognitive insight did not moderate the
      association between symptoms and well-being. The link between sub-clinical
      psychotic symptoms and psychological well-being as well as the insight paradox
      appears to emerge even before reaching threshold for a psychotic disorder.
      Research and clinical implications are discussed. 

PMID- 25618475
TI  - Neurocognitive functioning in the premorbid stage and in the first episode of
      bipolar disorder: a systematic review.
AB  - It is well known that patients with bipolar disorder (BD) have cognitive
      impairments even during periods of euthymia. However, to date it remains unclear
      the moment when these deficits onset. Therefore, the aim of this study was to
      review the evidence focusing on the cognitive status of patients with BD in their
      premorbid stage and in their first episode. An extensive search was conducted
      through the online databases Pubmed/PsychInfo, covering the period between 1980
      and 2014. A total of 23 studies were selected for the review (nine studies
      explored premorbid stage of people who lately develop BD and 14 examined first
      episodes in bipolar patients). There is evidence that general intelligence is not
      impaired in the premorbid stage. Impairments in verbal memory, attention, and
      executive functions tend to be present during and after the first episode.
      Preliminary evidence suggests that these deficits in specific cognitive domains
      might precede the onset of illness. 

PMID- 25618476
TI  - Assignment refusal and its relation to outcome in a randomized controlled trial
      comparing Cognitive Therapy and Fluvoxamine in treatment-resistant patients with
      obsessive compulsive disorder.
AB  - The effectiveness of Fluvoxamine was compared to that of Cognitive Therapy (CT)
      in a 12-week randomized controlled trial (RCT) in 48 patients with obsessive
      compulsive disorder (OCD), who were treatment-resistant to a previous behavior
      therapy (BT). A considerable amount of patients did not comply with the assigned
      treatment and switched treatments. The aim of this study was to identify patient
      characteristics predictive of assignment compliance and to study whether these
      characteristics were related to outcome. A logistic model, based on psychological
      and social patient characteristics, in addition to or in interaction with the
      assignment, was used for the explanation of compliance with treatment assignment.
      Especially patients who have a higher score on the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) tend to comply with the effective Fluvoxamine
      treatment. The same set of variables was related to both compliance and outcome
      of therapy received. Therefore, the logistic model of compliance could be used to
      reduce the positive bias of As-Treated analysis (AT). The difference between the
      results of Fluvoxamine and Cognitive Therapy remained statistically significant
      after correcting for the positive bias as the result of assignment refusal and
      after applying the assumption that two drop-out patients needed imputation of
      lesser results. 

PMID- 25618477
TI  - Toward new sensitive measures to evaluate gait stability in focal cerebellar
      lesion patients.
AB  - The evident ataxic characteristics of gait in patients with cerebellar damage
      suggest that the cerebellum plays an important role in the neural control of
      gait. Ataxic features, such as increased gait variability and increased step
      width, are often related to gait stability. However, the link between these
      measures and gait stability is not straightforward. Therefore, to gain more
      insights into relations between gait stability, gait variability and gait ataxia,
      we quantified gait stability using the short-term maximum Lyapunov exponent. This
      is a more valid measure of gait stability, derived from dynamical systems theory.
      Eighteen patients with focal cerebellar lesions after tumor resection walked on
      an instrumented treadmill at 1.0m/s for 3min. The patients displayed relatively
      mild functional deficits (ICARS=6.9+/-6.4, range 0-20) and had a lower overground
      walking speed as compared to healthy controls (1.12m/s versus 1.31m/s). During
      treadmill walking, the short-term maximum Lyapunov exponent was higher in
      cerebellar patients, indicating reduced gait stability. Furthermore, step width
      was increased in the patient group while other spatio-temporal gait parameters
      were similar. Patients with the largest lesions in the vermis displayed the least
      stable gait pattern. These observations imply that the short-term maximum
      Lyapunov exponent is a sensitive measure of gait deficits in mildly ataxic
      cerebellar patients.

PMID- 25618478
TI  - Reporting nuclear cardiology: a joint position paper by the European Association
      of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging
      (EACVI).
AB  - The report of an imaging procedure is a critical component of an examination,
      being the final and often the only communication from the interpreting physician
      to the referring or treating physician. Very limited evidence and few
      recommendations or guidelines on reporting imaging studies are available;
      therefore, an European position statement on how to report nuclear cardiology
      might be useful. The current paper combines the limited existing evidence with
      expert consensus, previously published recommendations as well as current
      clinical practices. For all the applications discussed in this paper (myocardial
      perfusion, viability, innervation, and function as acquired by single photon
      emission computed tomography and positron emission tomography or hybrid imaging),
      headings cover laboratory and patient demographics, clinical indication, tracer
      administration and image acquisition, findings, and conclusion of the report. The
      statement also discusses recommended terminology in nuclear cardiology, image
      display, and preliminary reports. It is hoped that this statement may lead to
      more attention to create well-written and standardized nuclear cardiology reports
      and eventually lead to improved clinical outcome. 

PMID- 25618480
TI  - Surfing the continuous and walking amongst molecules to unravel the mechanical
      properties of biomembranes.

PMID- 25618479
TI  - Pathology of gallbladder carcinoma: current understanding and new perspectives.
AB  - Gallbladder carcinoma is a rare and highly lethal malignancy. It stands out from
      amongst the other GI tract malignancies for its unique epidemiological profile,
      proclivity for female gender, definitional ambiguities, ability to escape early
      diagnosis, and absence of effective treatment. Pathobiology of gallbladder
      carcinoma continues to remain poorly understood. Recently, better
      characterization of the precursor lesions and elucidation of underlying molecular
      pathways has enhanced our understanding of gallbladder tumorigenesis. Proposal of
      a unified terminology and evolving consensus in classifying gallbladder pre
      invasive neoplasia offers hope of better assimilation of rare data from diverse
      parts of the world. Identifying biomarkers and cancer specific cellular targets
      that will pave the way for novel therapeutic approaches for gallbladder carcinoma
      is urgently needed. In this review we delve into the epidemiologic, genetic and
      pathologic characteristics of this enigmatic disease with a special focus on the
      recent advancements in the field of gallbladder pathology.

PMID- 25618481
TI  - Determinants of aortic bioprosthetic valve calcification assessed by
      multidetector CT.
AB  - BACKGROUND: Cusp calcification is the main mechanism leading to bioprosthetic
      heart valve (BPV) failure. Recent studies suggest that BPV calcification is an
      active rather than passive process probably modulated by several mechanisms
      including lipid-mediated inflammation and dysfunctional phosphocalcic metabolism.
      OBJECTIVE: To identify the clinical and metabolic determinants of BPV
      calcification assessed by multidetector CT (MDCT). METHODS AND RESULTS: Presence
      of BPV calcification was assessed by MDCT in 194 patients who had undergone
      aortic valve replacement. A calcification score was individually calculated and
      expressed in mm(3). Patients also underwent a clinical evaluation, a Doppler
      echocardiographic exam, and a plasma lipid and phosphocalcic profile. 46 patients
      (24%) had BPV calcification (cusp calcification score >0 mm(3)). After adjustment
      for age, gender, and time interval since BPV implantation, increased calcium
      phosphorus product (OR 1.11, 95% CI 1.01 to 1.23 per 1 unit; p=0.02) and the
      presence of prosthesis-patient mismatch (OR 3.67, 95% CI 1.25 to 10.6; p=0.01)
      were the strongest independent factors associated with BPV calcification. Calcium
      supplement intake, age and female gender were independently associated with
      increased calcium-phosphorus product. CONCLUSIONS: This study suggests that
      higher calcium-phosphorus product and prosthesis-patient mismatch promote BPV
      calcification. Furthermore, this study reports that calcium supplements, which
      are extensively prescribed in elderly patients, are independently associated with
      higher calcium-phosphorus product.

PMID- 25618482
TI  - Prosthetic rehabilitation for older dysvascular people following a unilateral
      transfemoral amputation.
AB  - BACKGROUND: Dysvascularity accounts for 75% of all lower limb amputations in the
      UK. Around 37% of these are at transfemoral level (mid-thigh), with the majority
      of people being over the age of 60 and having existing co-morbidities. A
      significant number of these amputees will be prescribed a lower limb prosthesis
      for walking. However, many amputees do not achieve a high level of function
      following prosthetic rehabilitation. This is the second update of the review
      first published in 2005. OBJECTIVES: We aimed to identify and summarise the
      evidence from randomised controlled trials evaluating rehabilitation
      interventions for prosthetic ambulation following unilateral transfemoral
      amputation in older dysvascular people, whether community dwelling or
      institutionalised. SEARCH METHODS: For this update the Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised
      Register (last searched July 2014) and Cochrane Register of Studies (CRS) (last
      searched 2014 Issue 6). No language restrictions were applied. SELECTION
      CRITERIA: Randomised and quasi-randomised controlled trials testing prosthetic
      rehabilitation interventions following a unilateral transfemoral or
      transgenicular amputation in older (aged 60 years or above) dysvascular people.
      DATA COLLECTION AND ANALYSIS: Two authors independently scanned the search
      results for potentially eligible studies and on obtaining full reports of these,
      selected studies for inclusion and exclusion. Two authors independently assessed
      methodological quality and extracted data. No data pooling was possible. MAIN
      RESULTS: No new studies were identified for inclusion in this update. Of the full
      reports obtained for consideration, one trial was included and four excluded. The
      included trial was a short-term crossover randomised trial which tested the
      effects of adding three seemingly identical prosthetic weights (150 g versus 770
      g versus 1625 g) to the prostheses of 10 participants with unilateral dysvascular
      transfemoral amputation. Eight participants were over 60 years of age. The trial
      found that four participants preferred the lightest weight (150 g), five
      preferred the middle weight (770 g) and one preferred the addition of the
      heaviest weight (1625 g). AUTHORS' CONCLUSIONS: There is a lack of evidence from
      randomised controlled trials to inform the choice of prosthetic rehabilitation,
      including the optimum weight of prosthesis, after unilateral transfemoral
      amputation in older dysvascular people. A programme of research, including
      randomised controlled trials to examine key interventions, is urgently required
      in this area.

PMID- 25618483
TI  - Should medicolegal medicine be part of the medical school curriculum?

PMID- 25618484
TI  - Plastic surgery spin: suppressing clarity.

PMID- 25618485
TI  - Smoking, food, and alcohol cues on subsequent behavior: a qualitative systematic
      review.
AB  - Although craving is a frequent phenomenon in addictive behaviors, and laboratory
      paradigms have robustly established that presentation of cues can elicit self
      reported craving responses, extant work has not established whether cue exposure
      influences subsequent behavior. We systematically review extant literature
      assessing the effects of cue exposure to smoking, food, and alcohol cues on
      behavioral outcomes framed by three questions: (1) Is there value in
      distinguishing between the effects of cue exposure on behavior from the responses
      to cues (e.g., self-reported craving) predicting behavior?; (2) What are the
      effect of cues on behavior beyond lapse, such as broadly considering both target
      syntonic (e.g., do cigarette cues predict smoking-related behaviors) and target
      dystonic behaviors (e.g., do cigarette cues predict other outcomes besides
      smoking)?; (3) What are the lessons to be learned from examining cue exposure
      studies across smoking, food and alcohol domains? Evidence generally indicates an
      effect of cue exposure on both target-syntonic and target-dystonic behavior, and
      that self-report cue-reactivity predicts immediate target-syntonic outcomes.
      Effects of smoking, food and alcohol cues on behavior are compared to elucidate
      generalizations about the effects of cue exposure as well as methodological
      differences that may serve the study of craving in the future. 

PMID- 25618486
TI  - Capillary migration of microdisks on curved interfaces.
AB  - The capillary energy landscape for particles on curved fluid interfaces is
      strongly influenced by the particle wetting conditions. Contact line pinning has
      now been widely reported for colloidal particles, but its implications in
      capillary interactions have not been addressed. Here, we present experiment and
      analysis for disks with pinned contact lines on curved fluid interfaces. In
      experiment, we study microdisk migration on a host interface with zero mean
      curvature; the microdisks have contact lines pinned at their sharp edges and are
      sufficiently small that gravitational effects are negligible. The disks migrate
      away from planar regions toward regions of steep curvature with capillary
      energies inferred from the dissipation along particle trajectories which are
      linear in the deviatoric curvature. We derive the curvature capillary energy for
      an interface with arbitrary curvature, and discuss each contribution to the
      expression. By adsorbing to a curved interface, a particle eliminates a patch of
      fluid interface and perturbs the surrounding interface shape. Analysis predicts
      that perfectly smooth, circular disks do not migrate, and that nanometric
      deviations from a planar circular, contact line, like those around a weakly
      roughened planar disk, will drive migration with linear dependence on deviatoric
      curvature, in agreement with experiment. 

PMID- 25618487
TI  - [Response to the letter from N. Nocart and J. Nizard].

PMID- 25618488
TI  - [Protein-losing enteropathy].
AB  - Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss.
      The primary causes can be classified into lymphatic leakage due to increased
      interstitial pressure and increased leakage of protein-rich fluids due to erosive
      or non-erosive gastrointestinal disorders. The diagnosis of protein-losing
      enteropathy should be considered in patients with chronic diarrhea and peripheral
      oedema. The diagnosis of protein-losing enteropathy is most commonly based on the
      determination of fecal alpha-1 antitrypsin clearance. Most protein-losing
      enteropathy cases are the result of either lymphatic obstruction or a variety of
      gastrointestinal disorders and cardiac diseases, while primary intestinal
      lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing
      enteropathy targets the underlying disease but also includes dietary
      modification, such as high-protein and low-fat diet along with medium-chain
      triglyceride supplementation. 

PMID- 25618489
TI  - No difference in revision rates between single- and double-bundle anterior
      cruciate ligament reconstruction: a comparative study of 16,791 patients from the
      Swedish national knee ligament register.
AB  - PURPOSE: The purpose was to compare revision rates and patient-reported outcomes
      between single- and double-bundle anterior cruciate ligament (ACL)
      reconstructions. METHODS: All patients from the Swedish National Knee Ligament
      Register from 2005 through 2011 who underwent primary ACL reconstruction with
      hamstring autografts were included. Patients with concomitant injuries, except
      meniscal and chondral injuries, were excluded. By December 31, 2011, 16,791
      primary isolated ACL reconstructions had been registered, of which 16,281 were
      single-bundle and 510 were double-bundle. Cumulative revision rates were
      estimated using Kaplan-Meier analysis. The Knee injury and Osteoarthritis Outcome
      Score (KOOS) and EQ-5D were calculated at 1- and 2-year follow-ups. RESULTS: The
      revision rate showed no statistically significant differences between the groups
      (P = .30). Over the 7-year observation period, 347 single-bundle (2.1%) and 8
      double-bundle (1.6%) ACL reconstructions were revised. No significant differences
      in the KOOS or EQ-5D were found between the groups postoperatively. In addition,
      there were no differences in postoperative improvements in the KOOS or EQ-5D at 1
      and 2-year follow-ups. CONCLUSIONS: Revision rates after single- and double
      bundle ACL reconstructions were low. No differences were found in revision rates,
      KOOS, and EQ-5D between the 2 techniques. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 25618490
TI  - Muscle and tendon injuries: the role of biological interventions to promote and
      assist healing and recovery.
AB  - PURPOSE: To summarize clinical studies after platelet-rich plasma (PRP) therapy
      for tendinopathy, plantar fasciopathy, and muscle injuries; to review PRP
      formulations used across studies; and to identify knowledge deficits that require
      further investigation. METHODS: After a systematic review in PubMed, we
      identified clinical studies assessing PRP efficacy in tendon and muscle during
      the past decade. We standardized data extraction by grouping studies based on
      anatomic location; summarized patient populations, PRP formulations, and clinical
      outcomes; and identified knowledge deficits that require further investigation.
      RESULTS: Overall, 1,541 patients had been treated with PRP in 58 clinical
      studies; of these, 26 addressed upper limb tendinopathies and 32 addressed the
      lower limb (810 patients and 731 patients treated with PRP, respectively). The
      quality of research is higher for the upper limb than for the lower limb (23
      controlled studies, of which 17 are Level I, v 19 controlled studies, of which 6
      are Level I, respectively). Patients have been treated mostly with leukocyte
      platelet-rich plasma, except in the arthroscopic management of the rotator cuff.
      The safety and efficacy of PRP for muscle injuries has been addressed in 7
      studies including 182 patients. Differences across results are mainly attributed
      to dissimilarities between tissues and different stages of degeneration, numbers
      of PRP applications, and protocols. CONCLUSIONS: Given the heterogeneity in
      tendons and tendinopathies, currently, we are not able to decide whether PRP
      therapies are useful. Despite advances in PRP science, data are insufficient and
      there is a clear need to optimize protocols and obtain more high-quality clinical
      data in both tendinopathies and muscle injuries before making treatment
      recommendations. LEVEL OF EVIDENCE: Level IV, systematic review of Level I
      through IV studies.

PMID- 25618491
TI  - Tissue engineering of ligaments for reconstructive surgery.
AB  - PURPOSE: The use of musculoskeletal bioengineering and regenerative medicine
      applications in orthopaedic surgery has continued to evolve. The aim of this
      systematic review was to address tissue-engineering strategies for knee ligament
      reconstruction. METHODS: A systematic review of PubMed/Medline using the terms
      "knee AND ligament" AND "tissue engineering" OR "regenerative medicine" was
      performed. Two authors performed the search, independently assessed the studies
      for inclusion, and extracted the data for inclusion in the review. Both
      preclinical and clinical studies were reviewed, and the articles deemed most
      relevant were included in this article to provide relevant basic science and
      recent clinical translational knowledge concerning "tissue-engineering"
      strategies currently used in knee ligament reconstruction. RESULTS: A total of
      224 articles were reviewed in our initial PubMed search. Non-English-language
      studies were excluded. Clinical and preclinical studies were identified, and
      those with a focus on knee ligament tissue-engineering strategies including stem
      cell-based therapies, growth factor administration, hybrid biomaterial, and
      scaffold development, as well as mechanical stimulation modalities, were
      reviewed. CONCLUSIONS: The body of knowledge surrounding tissue-engineering
      strategies for ligament reconstruction continues to expand. Presently, various
      tissue-engineering techniques have some potential advantages, including faster
      recovery, better ligamentization, and possibly, a reduction of recurrence.
      Preclinical research of these novel therapies continues to provide promising
      results. There remains a need for well-designed, high-powered comparative
      clinical studies to serve as a foundation for successful translation into the
      clinical setting going forward. LEVEL OF EVIDENCE: Level IV, systematic review of
      Level IV studies.

PMID- 25618492
TI  - Magnetic resonance imaging findings of the lateral collateral ligament and
      popliteus tendon in symptomatic knees without instability.
AB  - PURPOSE: To describe normative values of the thicknesses of the lateral
      collateral ligament (LCL) and popliteus tendon in patients who underwent knee
      surgery but had no evidence of knee instability and identify factors associated
      with the variations, and to estimate the prevalence and associated factors of
      abnormal magnetic resonance imaging (MRI) findings of the LCL and popliteus
      tendon. METHODS: MRI scans in 120 patients without knee instability were
      evaluated to measure the thicknesses of the LCL and popliteus tendon and estimate
      the prevalence of signal alteration and abnormal thickening and thinning. We then
      investigated the factors associated with the thicknesses and abnormal MRI
      findings. RESULTS: The mean thicknesses of the LCL and popliteus tendon were 5.3
      +/- 1.0 mm and 3.8 +/- 0.6 mm, respectively. Elderly, heavier patients and
      patients with more varus alignment had thicker LCLs, whereas taller, heavier, and
      male patients had thicker popliteus tendons. Signal alterations of the LCL and
      popliteus tendon were found in 33% and 23%, respectively, of the knees; abnormal
      thickening was found in 33% and 8%, respectively. Regression analyses found the
      mechanical tibiofemoral angle (more varus angle) to be the only predictor for
      abnormal MRI findings of the LCL (odds ratio of 0.81 [95% confidence interval,
      0.66 to 0.98] for signal alteration and odds ratio of 0.73 [95% confidence
      interval, 0.59 to 0.90] for abnormal thickening); however, no predictors were
      found for abnormal MRI findings of the popliteus tendon. CONCLUSIONS: Even in
      patients without varus and posterolateral rotary instability, signal alteration
      and thickening of the LCL and/or popliteus tendon can be frequently found with
      MRI. In particular, abnormal MRI findings of the LCL were likely to be more
      frequent in the patients with more varus knee alignment. These findings may be
      considered when interpreting MRI evaluation to diagnose patients with chronic
      posterolateral corner injury. LEVEL OF EVIDENCE: Level III, diagnostic study of
      nonconsecutive patients.

PMID- 25618493
TI  - Novel prediction model of renal function after nephrectomy from automated renal
      volumetry with preoperative multidetector computed tomography (MDCT).
AB  - BACKGROUND AND PURPOSE: The predictive model of postoperative renal function may
      impact on planning nephrectomy. To develop the novel predictive model using
      combination of clinical indices with computer volumetry to measure the preserved
      renal cortex volume (RCV) using multidetector computed tomography (MDCT), and to
      prospectively validate performance of the model. PATIENTS AND METHODS: Total 60
      patients undergoing radical nephrectomy from 2011 to 2013 participated, including
      a development cohort of 39 patients and an external validation cohort of 21
      patients. RCV was calculated by voxel count using software (Vincent, FUJIFILM).
      Renal function before and after radical nephrectomy was assessed via the
      estimated glomerular filtration rate (eGFR). Factors affecting postoperative eGFR
      were examined by regression analysis to develop the novel model for predicting
      postoperative eGFR with a backward elimination method. The predictive model was
      externally validated and the performance of the model was compared with that of
      the previously reported models. RESULTS: The postoperative eGFR value was
      associated with age, preoperative eGFR, preserved renal parenchymal volume (RPV),
      preserved RCV, % of RPV alteration, and % of RCV alteration (p < 0.01). The
      significant correlated variables for %eGFR alteration were %RCV preservation (r =
      0.58, p < 0.01) and %RPV preservation (r = 0.54, p < 0.01). We developed our
      regression model as follows: postoperative eGFR = 57.87 - 0.55(age) - 15.01(body
      surface area) + 0.30(preoperative eGFR) + 52.92(%RCV preservation). Strong
      correlation was seen between postoperative eGFR and the calculated estimation
      model (r = 0.83; p < 0.001). The external validation cohort (n = 21) showed our
      model outperformed previously reported models. CONCLUSIONS: Combining MDCT renal
      volumetry and clinical indices might yield an important tool for predicting
      postoperative renal function.

PMID- 25618494
TI  - Embolization of ruptured renal artery aneurysms.
AB  - BACKGROUND: Renal artery aneurysm (RAA) is a relatively rare vascular entity.
      Treatment of ruptured RAA could be either surgical or via an endovascular route
      with variable prognosis and remain controversial. To evaluate the results of
      ruptured renal artery aneurysms treated by endovascular treatment and explore the
      efficacy of selective embolization in ruptured RAAs, controlling hemorrhage, and
      preserving renal function. METHODS: From January 2001 to May 2011, 6 patients
      presented with gross hematuria or sudden onset severe abdominal or flank pain.
      This included a number in whom the aneurysm leaked, causing hematuria. Color
      Doppler ultrasonography (CDU) and contrasted computed tomography (CT) or computed
      tomography angiography (CTA) demonstrated 6 cases, and all cases were performed
      emergency angiography and 5 cases treated with selective coil embolization, and
      one case with trunk artery occlusion. RESULTS: All cases with a follow-up for
      mean 25 months (range 12-64 months),4 cases with selective coil embolization with
      complete durable occlusion was achieved in all aneurysms without relapse,
      patients' renal function was not significantly deteriorated. The case with trunk
      occlusion underwent subsequent ischemic parenchymal loss and post-embolization
      syndrome and with mild kidney atrophy. CONCLUSIONS: Superselective coil
      embolization provides a good therapeutic option for the ruptured RAAs with low
      mortality rates and good long-term outcome. RAAs have a probability of bilateral
      and multiple lesions,so attention for the presence of the contralateral RAA is
      important for medical choice.

PMID- 25618495
TI  - Antithrombotic treatment in elderly patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) in the elderly is a complex condition due to the high
      number of frequently associated comorbidities, such as cardiovascular and kidney
      disease, cognitive disorders, falls and polypharmacy. Except when
      contraindicated, anticoagulation is necessary for preventing thromboembolic
      events in this population. Both vitamin K antagonists and direct oral
      anticoagulants (dabigatran, rivaroxaban and apixaban) are indicated in this
      context. Renal function should be closely monitored for this age group when these
      drugs are used. In recent years, various clinical practice guidelines have been
      published on patients with AF. The majority of these guidelines make specific
      recommendations on the clinical characteristics and treatment of elderly
      patients. In this update, we review the specific comments on the recommendations
      concerning antithrombotic treatment in elderly patients with nonvalvular AF. 

PMID- 25618496
TI  - Effect of enzymatic pretreatment on anaerobic co-digestion of sugar beet pulp
      silage and vinasse.
AB  - Results of sugar beet pulp silage (SBPS) and vinasse (mixed in weight ratios of
      3:1, 1:1 and 1:3, respectively) co-fermentation, obtained in this study, provide
      evidence that addition of too high amount of vinasse into the SBPS decreases
      biogas yields. The highest biogas productivity (598.1mL/g VS) was achieved at the
      SBPS-vinasse ratio of 3:1 (w/w). Biogas yields from separately fermented SBPS and
      vinasse were by 13% and 28.6% lower, respectively. It was found that enzymatic
      pretreatment of SBPS before methane fermentation that caused partial degradation
      of component polysaccharides, considerably increased biogas production. The
      highest biogas yield (765.5mL/g VS) was obtained from enzymatic digests of SBPS
      vinasse (3:1) blend (27.9% more than from fermentation of the counterpart blend,
      which was not treated with enzymes). The simulation of potential biogas
      production from all the aforementioned mixtures using the Gompertz equation
      showed fair fit to the experimental results. 

PMID- 25618497
TI  - Fed-batch strategy for enhancing cell growth and C-phycocyanin production of
      Arthrospira (Spirulina) platensis under phototrophic cultivation.
AB  - The C-phycocyanin generated in blue-green algae Arthrospira platensis is gaining
      commercial interest due to its nutrition and healthcare value. In this study, the
      light intensity and initial biomass concentration were manipulated to improve
      cell growth and C-phycocyanin production of A.platensis in batch cultivation. The
      results show that low light intensity and high initial biomass concentration led
      to increased C-phycocyanin accumulation. The best C-phycocyanin productivity
      occurred when light intensity and initial biomass concentration were
      300MUmol/m(2)/s and 0.24g/L, respectively. The fed-batch cultivation proved to be
      an effective strategy to further enhance C-phycocyanin production of A.platensis.
      The results indicate that C-phycocyanin accumulation not only requires nitrogen
      sufficient condition, but also needs other nutrients. The highest C-phycocyanin
      content (16.1%), production (1034mg/L) and productivity (94.8mg/L/d) were
      obtained when using fed-batch strategy with 5mM medium feeding. 

PMID- 25618498
TI  - Thermogravimetric analysis of co-combustion between microalgae and textile dyeing
      sludge.
AB  - The synergistic interaction and kinetics of microalgae, textile dyeing sludge and
      their blends were investigated under combustion condition by thermogravimetric
      analysis. The textile dyeing sludge was blended with microalgae in the range of
      10-90wt.% to investigate their co-combustion behavior. Results showed that the
      synergistic interaction between microalgae and textile dyeing sludge improved the
      char catalytic effect and alkali metals melt-induced effect on the decomposition
      of textile dyeing sludge residue at high temperature of 530-800 degrees C. As the
      heating rate increasing, the entire combustion process was delayed but the
      combustion intensity was enhanced. The lowest average activation energy was
      obtained when the percentage of microalgae was 60%, which was 227.1kJ/mol by OFW
      and 227.4kJ/mol by KAS, respectively. 

PMID- 25618499
TI  - Effect of limited air exposure and comparative performance between thermophilic
      and mesophilic solid-state anaerobic digestion of switchgrass.
AB  - Switchgrass is an attractive feedstock for biogas production via anaerobic
      digestion (AD). Many studies have used switchgrass for liquid anaerobic digestion
      (L-AD), but few have used switchgrass for solid-state anaerobic digestion (SS
      AD). Limited air exposure to the reactor headspace has been adopted in commercial
      scale anaerobic digesters for different applications. However, little research
      has examined the effect of limited air exposure on biogas production during SS
      AD. In this study, the effects of air exposure and total solids (TS) content on
      SS-AD performance were evaluated under mesophilic (36+/-1 degrees C) and
      thermophilic (55+/-0.3 degrees C) conditions. Limited air exposure did not
      significantly influence the methane yield during SS-AD. Thermophilic SS-AD had
      greater methane yields (102-145LCH4kg(-1)VSadded) than mesophilic SS-AD (88
      113LCH4kg(-1)VSadded). Both mesophilic SS-AD (73-136GJ) and thermophilic SS-AD (2
      95GJ) produced positive net energy based on a theoretical 'garage-type' SS-AD
      digester operating in a temperate climate. 

PMID- 25618501
TI  - Dietary patterns, and effect on population health, get attention from advisory
      panel.

PMID- 25618500
TI  - Periconceptional folic acid supplementation among pregnant women with epilepsy in
      a developing country: a retroprospective survey in China.
AB  - OBJECTIVE: The aims of this study were to investigate the implementation of
      guidelines on periconceptional folic acid supplementation among pregnant women
      with epilepsy (WWE) in China and to identify its potential correlations with
      selected sociodemographic and clinical factors. METHODS: A detailed investigation
      was conducted in China using a structured questionnaire from December 2013 to May
      2014. Data on the awareness and use of folic acid supplementation, as well as
      sociodemographic and clinical characteristics, were collected from 153 pregnant
      WWE. Descriptive analysis, followed by univariate and multivariate logistic
      regression analyses, was applied to the data from this survey. RESULTS: Among the
      enrolled subjects, 67.3% became pregnant after the promulgation of the relevant
      guidelines. Only 26.2% of them knew the exact effects of folic acid, and 73.8%
      had taken folic acid at some point during periconception. In addition, the folic
      acid intake of most of these women (67.1%) did not exceed that of the average
      pregnant woman. The prevalence of folic acid supplementation for pregnant WWE
      three months before pregnancy was only 15.5%. There has been almost no
      improvement in the level of additional awareness and use of folic acid
      supplementation for WWE since the relevant guidelines were established in China.
      Pregnant WWE with higher education levels, those with a planned pregnancy, or
      those who live in urban areas were more likely to know about and implement folic
      acid supplementation during periconception. Moreover, pregnant WWE with a planned
      pregnancy or those living in cities seemed to have a higher folic acid intake and
      started folic acid supplementation earlier before conception. CONCLUSION: The
      extent of awareness and use of folic acid supplementation in pregnant WWE remains
      low in China. More efforts are needed to promote periconceptional folic acid
      supplementation for WWE, especially those with low education levels and those who
      live in rural areas. Planned pregnancy should be encouraged for WWE.

PMID- 25618502
TI  - The continuing evolution of employer-based intervention in diabetes disease
      management.

PMID- 25618503
TI  - Study on protective gene mutations for T2DM appears to have strong implications
      for drug development.

PMID- 25618504
TI  - A big step forward in treating chronic diabetic foot ulcers.

PMID- 25618505
TI  - New studies affirm Mediterranean diet's potential for patient self-management,
      prevention of T2DM.

PMID- 25618506
TI  - Evidence shows taking part in school nutrition programs helps students make
      better dietary choices.

PMID- 25618507
TI  - The link between a common type of bariatric surgery and increased alcohol use.

PMID- 25618508
TI  - My initial impressions of Medtronic's new pump.

PMID- 25618509
TI  - What is the place of new SGLT-2 inhibitors in therapy and on the formulary?

PMID- 25618510
TI  - Evidence-based diabetes protocol development: approaches and a case study.

PMID- 25618511
TI  - Managing the transition to adulthood with type 1 diabetes mellitus; an interview
      with Robert Kritzler, MD.

PMID- 25618512
TI  - New orphan drug in the T1DM realm: another immunotherapy success story?

PMID- 25618513
TI  - OSH officials discuss how 50th anniversary report highlights link between
      smoking, diabetes.

PMID- 25618514
TI  - Germination induction of dormant Avena fatua caryopses by KAR(1) and GA(3)
      involving the control of reactive oxygen species (H2O2 and O2(.-)) and enzymatic
      antioxidants (superoxide dismutase and catalase) both in the embryo and the
      aleurone layers.
AB  - Avena fatua L. caryopses did not germinate at 20  degrees C in darkness because
      they were dormant. However, they were able to germinate in the presence of
      karrikinolide (KAR1), a key bioactive compound present in smoke, and also in the
      presence of gibberellin A3 (GA3), a commonly known stimulator of seed
      germination. The aim of this study was to collect information on a possible
      relationship between the above regulators and abscisic acid (ABA), reactive
      oxygen species (ROS) and ROS scavenging antioxidants in the regulation of dormant
      caryopses germination. KAR1 and GA3 caused complete germination of dormant A.
      fatua caryopses. Hydrogen peroxide (H2O2), compounds generating the superoxide
      (O2(.-)), i.e. menadione (MN), methylviologen (MV) and an inhibitor of catalase
      activity, aminotriazole (AT), induced germination of dormant caryopses. KAR1,
      GA3, H2O2 and AT decreased ABA content in embryos. Furthermore, KAR1, GA3, H2O2,
      MN, MV and AT increased alpha-amylase activity in caryopses. The effect of KAR1
      and GA3 on ROS (H2O2, O2(.-)) and activities of the superoxide dismutase (SOD)
      and catalase (CAT) were determined in caryopses, embryos and aleurone layers. SOD
      was represented by four isoforms and catalase by one. In situ localization of ROS
      showed that the effect of KAR1 and GA3 was associated with the localization of
      hydrogen peroxide mainly on the coleorhiza. However, the superoxide was mainly
      localized on the surface of the scutellum. Superoxide was also detected in the
      protruding radicle. Germination induction of dormant caryopses by KAR1 and GA3
      was related to an increasing content of H2O2, O2(.-)and activities of SOD and CAT
      in embryos, thus ROS homeostasis was probably required for the germination of
      dormant caryopses. The above regulators increased the content of ROS in aleurone
      layers and decreased the activities of SOD and CAT, probably leading to the
      programmed cell death. The presented data provide new insights into the
      germination induction of A. fatua dormant caryopses by KAR1 and also by GA3. In
      A. fatua, KAR1 or GA3 is included in the induction germination of dormant
      caryopses through regulation level of ABA in embryos and ROS-antioxidant status
      both in embryos and aleurone layers.

PMID- 25618515
TI  - Left Ventricular Systolic Dysfunction in Asymptomatic Black Hypertensive
      Subjects.
AB  - BACKGROUND: Hypertension has been established as one of the commonest causes of
      heart failure especially in sub-Saharan Africa. We have previously observed a
      high prevalence of left ventricular (LV) systolic dysfunction in hypertensive
      heart failure patients in Nigeria despite a low prevalence of ischemic heart
      disease. The present study was, therefore, undertaken to assess the prevalence of
      asymptomatic LV systolic dysfunction in hypertensive black African subjects with
      no history of heart failure. METHODS: One thousand nine hundred forty-seven
      hypertensive subjects without heart failure presenting to the Cardiology Unit,
      Department of Medicine, University of Abuja Teaching Hospital, Nigeria, from
      April 2006 to August 2013 had clinical and echocardiographic evaluation. RESULTS:
      Nine hundred fifty-three (48.9%) were males and 994 (51.1%) were females. One
      thousand eight hundred seventeen (93.3%) had normal LV systolic function (LV
      ejection fraction (LVEF) >= 54%), 68 (3.5%) had mild LV systolic dysfunction
      (LVEF 45-54%), 43 (2.3%) had moderate LV systolic dysfunction (LVEF 30-44%), and
      16 (0.9%) had severe LV systolic dysfunction (LVEF < 30%). Male subjects had
      worse LV systolic function compared to women (mean LVEF 73.2% vs. 75.6%, P value
      < 0.0001) and diabetic subjects had worse LV systolic function compared to
      nondiabetic subjects (LVEF 72.3% vs. 75.7%, P = 0.02). In multivariate regression
      analysis, lower LVEF as a continuous variable was associated with older age, male
      sex, diabetes mellitus, LV mass indexed for body surface area, diastolic blood
      pressure, posterior wall thickness in diastole, left atrial diameter, and LV
      internal diameter in diastole. CONCLUSIONS: In a cohort of asymptomatic Black
      hypertensive subjects, 6.7% had LV systolic dysfunction, which was associated
      with male gender, diabetes mellitus, and larger LV mass.

PMID- 25618516
TI  - Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher
      Body Mass Index.
AB  - BACKGROUND: The objective of this study was to investigate the genetic
      association of 4 candidate variants with blood pressure and test the modifying
      effects of environmental factors including age, sex, and body mass index (BMI).
      METHODS: We used a linear mixed-effects model to test for variant main effects
      and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic
      (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition
      Survey (CHNS). We attempted to replicate our significant interaction findings in
      1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey
      (FAMHES). RESULTS: Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5)
      were significantly associated (P < 0.00625 = 0.05/8) with both SBP and DBP in
      CHNS. Variant rs1378942 near CSK was nominally associated with SBP (P = 0.01).
      The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood
      pressure (P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with
      the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038
      also showed stronger effects on SBP and DBP among men with the highest BMI.
      CONCLUSIONS: Our findings suggest high BMI increases the effect of the blood
      pressure-increasing allele at rs1458038 near FGF5, further highlighting the
      importance of obesity prevention in reducing hypertension risk.

PMID- 25618517
TI  - Prevalence of Prehypertension in Mexico and Its Association With Hypomagnesemia.
AB  - BACKGROUND: Prehypertension (preHTN) increases the risk of developing
      hypertension. The objectives of this study were to estimate the prevalence of
      preHTN in the Mexican adult population and evaluate the association between
      hypomagnesemia and preHTN. METHODS: This study was a 2-phase, population-based
      study. In the first phase, 4,272 Mexican adults (aged 20-65 years) were enrolled
      to determine the prevalence of preHTN. In the second phase, a cross-sectional
      analysis was performed to evaluate the association between hypomagnesemia and
      preHTN. The exclusion criteria were chronic diarrhea, malignancy, hepatic and
      renal diseases, chronic inflammatory disease, and the intake of magnesium
      supplements. PreHTN was defined as a systolic blood pressure (BP) of 120-139 mm
      Hg and/or diastolic BP of 80-89 mm Hg, and hypomagnesemia was defined as a serum
      magnesium concentration <1.8 mg/dl. RESULTS: The prevalence of preHTN was 37.5%
      (95% confidence interval (CI): 36.0-39.0): 46.7% were men (95% CI: 44.1-49.4) and
      33.2% (95% CI: 31.5-5.0) were women. The serum magnesium data were available for
      921 participants. Hypomagnesemia was identified in 276 (30.0%; 95% CI: 27.1-33.0)
      subjects; of them, 176 (63.8%; 95% CI: 58.3-69.6) had preHTN. Individuals with
      preHTN exhibited lower magnesium levels than individuals without preHTN (1.78+/
      0.36 vs. 1.95+/-0.37, P < 0.0005). A multiple logistic regression analysis
      (adjusted for age, sex, smoking, body mass index, waist circumference, fasting
      glucose, total cholesterol, high-density lipoprotein cholesterol, and
      triglycerides levels) indicated a significant association between hypomagnesemia
      and preHTN (odds ratio = 1.78; 95% CI: 1.5-4.0, P < 0.0005). CONCLUSIONS: The
      prevalence of preHTN in the Mexican population is 37.5%, and hypomagnesemia is
      strongly associated with preHTN.

PMID- 25618519
TI  - Long-term monitoring of molecular markers can distinguish different seasonal
      patterns of fecal indicating bacteria sources.
AB  - Elevated levels of fecal indicator bacteria (FIB) have been observed at Topanga
      Beach, CA, USA. To identify the FIB sources, a microbial source tracking study
      using a dog-, a gull- and two human-associated molecular markers was conducted at
      10 sites over 21 months. Historical data suggest that episodic discharge from the
      lagoon at the mouth of Topanga Creek is the main source of bacteria to the beach.
      A decline in creek FIB/markers downstream from upper watershed development and a
      sharp increase in FIB/markers at the lagoon sites suggest sources are local to
      the lagoon. At the lagoon and beach, human markers are detected sporadically, dog
      marker peaks in abundance mid-winter, and gull marker is chronically elevated.
      Varied seasonal patterns of FIB and source markers were identified showing the
      importance of applying a suite of markers over long-term spatial and temporal
      sampling to identify a complex combination of sources of contamination. 

PMID- 25618518
TI  - Antidepressant-like effect of sodium butyrate is associated with an increase in
      TET1 and in 5-hydroxymethylation levels in the Bdnf gene.
AB  - BACKGROUND: Epigenetic drugs like sodium butyrate (NaB) show antidepressant-like
      effects in preclinical studies, but the exact molecular mechanisms of the
      antidepressant effects remain unknown. While research using NaB has mainly
      focused on its role as a histone deacetylase inhibitor (HDACi), there is also
      evidence that NaB affects DNA methylation. METHODS: The purpose of this study was
      to examine NaB's putative antidepressant-like efficacy in relation to DNA
      methylation changes in the prefrontal cortex of an established genetic rat model
      of depression (the Flinders Sensitive Line [FSL]) and its controls (the Flinders
      Resistant Line). RESULTS: The FSL rats had lower levels of ten-eleven
      translocation methylcytosine dioxygenase 1 (TET1), which catalyzes the conversion
      of DNA methylation to hydroxymethylation. As indicated by the behavioral despair
      test, chronic administration of NaB had antidepressant-like effects in the FSL
      and was accompanied by increased levels of TET1. The TET1 upregulation was also
      associated with an increase of hydroxymethylation and a decrease of methylation
      in brain-derived neurotrophic factor (Bdnf), a gene associated with neurogenesis
      and synaptic plasticity. These epigenetic changes were associated with a
      corresponding BDNF overexpression. CONCLUSIONS: Our data support the
      antidepressant efficacy of HDACis and suggest that their epigenetic effects may
      also include DNA methylation changes that are mediated by demethylation
      facilitating enzymes like TET1.

PMID- 25618520
TI  - Fungal diversity and presence of potentially pathogenic fungi in a hospital hot
      water system treated with on-site monochloramine.
AB  - Currently, our knowledge of fungal ecology in engineered drinking water systems
      is limited, despite the potential for these systems to serve as a reservoir for
      opportunistic pathogens. In this study, hot water samples were collected both
      prior to and following the addition of monochloramine as an on-site disinfectant
      in a hospital hot water system. Fungal ecology was then analyzed by high
      throughput sequencing of the fungal ITS1 region. The results demonstrate that the
      genera Penicillium, Aspergillus, Peniophora, Cladosporium and Rhodosporidium
      comprised the core fungal biome of the hospital hot water system. Penicillium
      dominated the fungal community with an average relative abundance of 88.89% (+/
      6.37%). ITS1 sequences of fungal genera containing potential pathogens such as
      Aspergillus, Candida, and Fusarium were also detected in this study. No
      significant change in fungal community structure was observed before and after
      the initiation of on-site monochloramine water treatment. This work represents
      the first report of the effects of on-site secondary water disinfection on fungal
      ecology in premise plumbing system, and demonstrates the necessity of considering
      opportunistic fungal pathogens during the evaluation of secondary premise
      plumbing disinfection systems. 

PMID- 25618521
TI  - Effect of bacterial communities on the formation of cast iron corrosion tubercles
      in reclaimed water.
AB  - To understand the role bacterial communities play in corrosion scale development,
      the morphological and physicochemical characteristics of corrosion scales in raw
      and disinfected reclaimed water were systematically investigated. Corrosion
      tubercles were found in raw reclaimed water while thin corrosion layers formed in
      disinfected reclaimed water. The corrosion tubercles, composed mainly of alpha
      FeOOH, gamma-FeOOH, and CaCO3, consisted of an top surface; a shell containing
      more magnetite than other layers; a core in association with stalks produced by
      bacteria; and a corroded layer. The thin corrosion layers also had layered
      structures. These had a smooth top, a dense middle, and a corroded layer. They
      mostly consisted of the same main components as the tubercles in raw reclaimed
      water, but with different proportions. The profiles of the dissolved oxygen (DO)
      concentration, redox potential, and pH in the tubercles were different to those
      in the corrosion layers, which demonstrated that these parameters changed with a
      shift in the microbial processes in the tubercles. The bacterial communities in
      the tubercles were found to be dominated by Proteobacteria (56.7%), Bacteroidetes
      (10.0%), and Nitrospira (6.9%). The abundance of sequences affiliated to iron
      reducing bacteria (IRB, mainly Geothrix) and iron-oxidizing bacteria (mainly
      Aquabacterium) was relatively high. The layered characteristics of the corrosion
      layers was due to the blocking of DO transfer by the development of the scales
      themselves. Bacterial communities could at least promote the layering process and
      formation of corrosion tubercles. Possible mechanisms might include: (1)
      bacterial communities mediated the pH and redox potential in the tubercles (which
      helped to form shell-like and core layers), (2) the metabolism of IRB and
      magnetic bacteria (Magnetospirillum) might contribute to the presence of Fe3O4 in
      the shell-like layer, while IRB contributed to green rust in the core layer, and
      (3) the diversity of the bacterial community resulted in the complex composition
      of the core layer, and gas producing bacteria (sulfate-reducing bacteria and
      methanogenic bacteria) played a role in the formation of the porous core layer. 

PMID- 25618522
TI  - Novel regeneration method for phosphate loaded granular ferric (hydr)oxide--a
      contribution to phosphorus recycling.
AB  - At a progressive rate, small wastewater treatment plants in rural areas need to
      be equipped with an additional phosphorus removal stage in order to achieve a
      good chemical status in the receiving natural water bodies. A conventional
      regeneration method for ferric (hydr)oxides such as phosphate specific
      adsorbents, which can be applied to remove and recover phosphorus in fixed bed
      filters, was investigated and improved. It was shown that a loss of up to 85% of
      the initial capacity can be observed when regeneration with 1 M NaOH is
      implemented. The losses are caused by surface blocking with different calcium
      containing compounds as revealed by an EDX analysis. These blocking compounds
      could be removed completely with an additional acidic regeneration step at pH =
      2.5. During the alkaline desorption that followed, complete phosphorus removal
      and a full recovery of the adsorption capacity were achieved for goethite-rich
      Bayoxide((r)) E 33 HC (E33HC) and akaganeite-rich GEH((r)) 104 (GEH). The
      regeneration procedure was repeated up to eight times without any signs of
      further decline in the phosphate adsorption capacity or any changes in the
      specific surface area or pore size distribution of the adsorbent. In contrast to
      GEH and E33HC, ferric hydroxide- and calcite-rich FerroSorp((r)) Plus (FSP) was
      partly dissolved during acid treatment. 

PMID- 25618523
TI  - Polycyclic aromatic hydrocarbons in sediments at dredged material disposal sites
      around England: concentrations in 2013 and time trend information at selected
      sites 2008-2013.
AB  - The maintenance of navigation channels to ports and the development of their
      facilities present a need to conduct dredging operations, and the subsequent
      disposal of dredged material at sea. Contaminant concentrations in candidate
      dredged material are determined and their possible impacts considered during the
      licensing process, which can result in the exclusion of some material from sea
      disposal. Monitoring of disposal sites is conducted in order to ensure that no
      undesirable impacts are occurring. In this study we consider the levels of
      polycyclic aromatic hydrocarbons (PAHs) in sediments at a number of disposal
      sites monitored in 2013 and variations in concentrations over time at three sites
      during the period 2008-2013. These were assessed using established sediment
      quality guidelines. Elevated PAH concentrations were generally observed only
      within the boundaries of the disposal sites studied. 

PMID- 25618524
TI  - Coordinative modulation of human zinc transporter 2 gene expression through
      active and suppressive regulators.
AB  - Zinc transporter 2 (ZnT2) is one of the cellular factors responsible for Zn
      homeostasis. Upon Zn overload, ZnT2 reduces cellular Zn by transporting it into
      excretory vesicles. We investigated the molecular mechanism that regulates human
      ZnT2 (hZnT2) gene expression. Zn induces hZnT2 expression in dose- and time
      dependent manners. Overexpression of metal-responsive transcription factor 1 (MTF
      1) increases hZnT2 transcription, whereas depletion of MTF-1 reduces hZnT2
      expression. There are five putative metal response elements (MREs) within 1kb
      upstream of the hZnT2 gene. A serial deletion of the hZnT2 promoter region (from
      5' to 3') shows that the two MREs proximal to the gene are essential for Zn
      induced promoter activity. Further mutation analysis concludes that the
      penultimate MRE (MREb) supports the metal-induced promoter activity. The hZnT2
      promoter has also a zinc finger E-box binding homeobox (ZEB) binding element.
      Mutation or deletion of this ZEB binding element elevates the basal and Zn
      induced hZnT2 promoter activities. Knockdown of ZEB1 mRNA enhances the hZnT2
      transcript level in HEK-293 cells. In MCF-7 (ZEB-deficient) cells, expression of
      ZEB proteins attenuates the Zn-induced hZnT2 expression. However, expressions of
      MTF-1 target genes such as human ZnT1 and metallothionein IIA were not affected.
      Our study shows the expression of the hZnT2 gene is coordinately regulated via
      active and suppressive modulators. 

PMID- 25618525
TI  - Appendectomy and resection of the terminal ileum with secondary severe necrotic
      changes in acute perforated appendicitis.
AB  - BACKGROUND: Resectional procedures for advanced and complicated appendicitis are
      performed infrequently. Their extent can vary: cecal resection, ileocecectomy,
      and even right hemicolectomy. We present a very rare case of appendectomy that
      was combined with partial ileal resection for severe necrotic changes and small
      perforation of the ileum. CASE REPORT: A 19-year-old female patient was
      hospitalized with right iliac fossa pain and fever 10 days after the onset of
      symptoms. On laparoscopy, a large mass in a right iliac fossa was found. The
      ultrasound-guided drainage of the suspected appendiceal abscess was unavailable.
      After conversion using McBurney's incision, acute perforated appendicitis was
      diagnosed. It was characterized by extension of severe necrotic changes onto the
      ileal wall and complicated by right iliac fossa abscess. A mass was bluntly
      divided, and a large amount of pus with fecaliths was discharged and evacuated.
      Removal of necrotic tissues from the ileal wall led to the appearance of a small
      defect in the bowel. A standard closure of this defect was considered as very
      unsafe due to a high risk of suture leakage or bowel stenosis. We perform a
      resection of the involved ileum combined with appendectomy and drainage/tamponade
      of an abscess cavity. Postoperative recovery was uneventful. The patient was
      discharged on the 15th day. CONCLUSIONS: In advanced appendicitis, the involved
      bowel resection can prevent possible complications (e.g., ileus, intestinal
      fistula, peritonitis, and intra-abdominal abscess). Our case may be the first
      report of an appendectomy combined with an ileal resection for advanced and
      complicated appendicitis.

PMID- 25618526
TI  - Caseous calcification of the mitral annulus associated with stroke: report of two
      cases.
AB  - OBJECTIVE: Caseous calcification of the mitral annulus (CCAM) is a rare
      complication of mitral annulus calcification (MAC). Whether CCAM should be
      considered as a cardiac source of stroke or a simple marker of atherosclerosis
      remains a matter of debate. METHOD: Herein, we report two patients with stroke
      and CCAM. RESULTS: The first one was associated with extensive aortic arch
      atheroma, while CCAM was the only potential cause in the second case.
      Transthoracic echocardiography was normal in both cases and CCAM was diagnosed on
      transesophageal echocardiography. CONCLUSION: These observations suggest that
      CCAM should be added to the list of minor cardioembolic sources of stroke but
      also requires a perfect control of vascular risk factors.

PMID- 25618527
TI  - [A case of "CLIPPERS" cured by immunotherapy five years before the description of
      the syndrome].

PMID- 25618529
TI  - Bridge to recovery and myocardial cell division: a paradigm shift?

PMID- 25618528
TI  - Physiological and pathophysiological functions of cell cycle proteins in post
      mitotic neurons: implications for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder for
      which no effective treatment is available. Increased insight into the disease
      mechanism in early stages of pathology is required for the development of a
      successful therapy. Over the years, numerous studies have shown that cell cycle
      proteins are expressed in neurons of AD patients. Traditionally, neurons are
      considered to be post-mitotic, which means that they permanently retract from the
      cell cycle. The expression of cell cycle proteins in adult neurons of AD patients
      has therefore been suggested to promote or even instigate pathomechanisms
      underlying AD. Interestingly, expression of cell cycle proteins is detected in
      post-mitotic neurons of healthy controls as well, albeit to a lesser extent than
      in AD patients. This indicates that cell cycle proteins may serve important
      physiological functions in differentiated neurons. Here, we provide an overview
      of studies that support a role of cell cycle proteins in DNA repair and
      neuroplasticity in post-mitotic neurons. Aberrant control of these processes
      could, in turn, contribute to cell cycle-mediated neurodegeneration. The balance
      between regenerative and degenerative effects of cell cycle proteins in post
      mitotic neurons might change throughout the different stages of AD. In the early
      stages of AD pathology, cell cycle protein expression may primarily occur to aid
      in the repair of sublethal double-strand breaks in DNA. With the accumulation of
      pathology, cell cycle-mediated neuroplasticity and neurodegeneration may become
      more predominant. Understanding the physiological and pathophysiological role of
      cell cycle proteins in AD could give us more insight into the neurodegenerative
      process in AD.

PMID- 25618531
TI  - You say you want a (food) revolution.

PMID- 25618530
TI  - Human ventricular unloading induces cardiomyocyte proliferation.
AB  - BACKGROUND: The adult mammalian heart is incapable of meaningful regeneration
      after substantial cardiomyocyte loss, primarily due to the inability of adult
      cardiomyocytes to divide. Our group recently showed that mitochondria-mediated
      oxidative DNA damage is an important regulator of postnatal cardiomyocyte cell
      cycle arrest. However, it is not known whether mechanical load also plays a role
      in this process. We reasoned that the postnatal physiological increase in
      mechanical load contributes to the increase in mitochondrial content, with
      subsequent activation of DNA damage response (DDR) and permanent cell cycle
      arrest of cardiomyocytes. OBJECTIVES: The purpose of this study was to test the
      effect of mechanical unloading on mitochondrial mass, DDR, and cardiomyocyte
      proliferation. METHODS: We examined the effect of human ventricular unloading
      after implantation of left ventricular assist devices (LVADs) on mitochondrial
      content, DDR, and cardiomyocyte proliferation in 10 matched left ventricular
      samples collected at the time of LVAD implantation (pre-LVAD) and at the time of
      explantation (post-LVAD). RESULTS: We found that post-LVAD hearts showed up to a
      60% decrease in mitochondrial content and up to a 45% decrease in cardiomyocyte
      size compared with pre-LVAD hearts. Moreover, we quantified cardiomyocyte nuclear
      foci of phosphorylated ataxia telangiectasia mutated protein, an upstream
      regulator of the DDR pathway, and we found a significant decrease in the number
      of nuclear phosphorylated ataxia telangiectasia mutated foci in the post-LVAD
      hearts. Finally, we examined cardiomyocyte mitosis and cytokinesis and found a
      statistically significant increase in both phosphorylated histone H3-positive,
      and Aurora B-positive cardiomyocytes in the post-LVAD hearts. Importantly, these
      results were driven by statistical significance in hearts exposed to longer
      durations of mechanical unloading. CONCLUSIONS: Prolonged mechanical unloading
      induces adult human cardiomyocyte proliferation, possibly through prevention of
      mitochondria-mediated activation of DDR.

PMID- 25618532
TI  - Melatonin implants do not alter estrogen feedback or advance puberty in gilts.
AB  - Puberty in pigs is often delayed during late summer and autumn, with long
      daylength the most likely cause. We hypothesised (1) that gilts born around the
      shortest day would have a later release from the negative feedback actions of
      estradiol than gilts born around the spring equinox and (2) melatonin treatment
      would result in an earlier release from estradiol negative feedback and advance
      the onset of puberty in gilts born around the spring equinox. We first determined
      the optimal number of estradiol implants required to monitor the release from
      estradiol negative feedback in ovariectomised gilts. Secondly we determined
      whether melatonin implants altered negative feedback in 4 cohorts of
      ovariectomised gilts born between the winter solstice and spring equinox, and in
      the following year whether melatonin altered the time of the first ovulation in 5
      cohorts of intact gilts born between the winter solstice and spring equinox.
      Plasma LH and FSH increased between 126 and 210d of age (P<0.001) in each cohort
      (season), but there was no effect of cohort, melatonin treatment or interactions
      (P>0.05). Age at first detection of elevated plasma progesterone in untreated,
      intact gilts decreased across the 4 cohorts (P<0.05). Melatonin treatment of
      intact gilts failed to advance the age of puberty irrespective of their season of
      birth (P>0.05). In conclusion, while we confirmed that estradiol sensitivity is
      decreased as gilts age, we failed to demonstrate any effects of season or
      melatonin on estradiol feedback or melatonin on puberty. 

PMID- 25618533
TI  - Relationship between the size of the dominant follicle, vaginal electrical
      resistance, serum concentrations of oestradiol and progesterone and sexual
      receptivity during the follicular phase of the dromedary camel (Camelus
      dromedarius).
AB  - Thirteen dromedaries were used to study the relationship between the size of the
      dominant follicle, vaginal electrical resistance (VER), sexual receptivity, and
      serum concentrations of oestradiol-17beta (E2) and progesterone (P4) throughout
      the follicular phase. On a daily basis, the animals experienced teasing with a
      vasectomised camel, trans-rectal ultrasound examination of the ovaries, and
      measurement of VER and blood collection for serum E2 and P4. Results revealed no
      significant differences between the mean VER in the animals that had a follicle
      of 5-10mm (group I, n=11), 11-15mm (group II, n=12) and 16-20mm (group III,
      n=13). The VER did not correlate with the follicular size. The E2 concentrations
      in the animals in groups II (60.14pg/ml) and III (66.52pg/ml) were significantly
      (P<0.05) higher than those of animals in group I (48.31pg/ml). E2 was positively
      correlated (r=0.50; P<0.05) with the overall size of the follicles. The P4
      concentration was significantly (P<0.05) lower in the animals of group II than in
      those in groups I and III. Serum P4 concentrations were inversely correlated (r=
      0.40; P<0.05) with the overall size of the follicles. Complete sexual receptivity
      was reported in 63.64%, 16.67% and 76.92% of the animals in groups I, II and III,
      respectively. In group III, significant (P<0.05) complete sexual receptivity was
      confirmed. However, 23.08% of the animals were incompletely receptive. In
      conclusion, impedometric characteristics of the vaginal mucosa were not a
      reliable method for predicting the dominant follicular size during the follicular
      phase in dromedary camels. 

PMID- 25618534
TI  - World Health Organization strong recommendations based on low-quality evidence
      (study quality) are frequent and often inconsistent with GRADE guidance.
AB  - OBJECTIVES: In 2007 the World Health Organization (WHO) adopted the GRADE system
      for development of public health guidelines. Previously we found that many strong
      recommendations issued by WHO are based on evidence for which there is only low
      or very low confidence in the estimates of effect (discordant recommendations).
      GRADE guidance indicates that such discordant recommendations are rarely
      appropriate but suggests five paradigmatic situations in which discordant
      recommendations may be warranted. We sought to provide insight into the many
      discordant recommendations in WHO guidelines. STUDY DESIGN AND SETTING: We
      examined all guidelines that used the GRADE method and were approved by the WHO
      Guideline Review Committee between 2007 and 2012. Teams of reviewers
      independently abstracted data from eligible guidelines and classified
      recommendations either into one of the five paradigms for appropriately
      formulated discordant recommendations or into three additional categories in
      which discordant recommendations were inconsistent with GRADE guidance: 1) the
      evidence warranted moderate or high confidence (a misclassification of evidence)
      rather than low or very low confidence; 2) good practice statements; or 3)
      uncertainty in the estimates of effect would best lead to a conditional (weak)
      recommendation. RESULTS: The 33 eligible guidelines included 160 discordant
      recommendations, of which 98 (61.3%) addressed drug interventions and 132 (82.5%)
      provided some rationale (though not entirely explicit at times) for the strong
      recommendation. Of 160 discordant recommendations, 25 (15.6%) were judged
      consistent with one of the five paradigms for appropriate recommendations; 33
      (21%) were based on evidence warranting moderate or high confidence in the
      estimates of effect; 29 (18%) were good practice statements; and 73 (46%)
      warranted a conditional, rather than a strong recommendation. CONCLUSION: WHO
      discordant recommendations are often inconsistent with GRADE guidance, possibly
      threatening the integrity of the process. Further training in GRADE methods for
      WHO guideline development group members may be necessary, along with further
      research on what motivates the formulation of such recommendations.

PMID- 25618535
TI  - [Pudendal nerve block for perineo-vulvar surgery: monocentered prospective and
      randomised study].
AB  - OBJECTIVES: Evaluation of pudendal nerve block on the quality of analgesia in
      perineal or vulvar surgery. PATIENTS AND METHODS: We realised a monocentered,
      prospective and randomised study of all patients undergoing perineo-vulvar
      surgery. Two groups of patients were evaluated: general anaesthesia alone (GA
      group, 41 patients) and both general anaesthesia and bilateral nerve stimulator
      guided pudendal nerve block (15 mL of Ropivacaine 5 mg.mL(-1)+0,5 MUg.kg(-1) of
      Clonidine) (PB group, 42 patients). Evaluation of pain was realised with per- and
      post-surgical prescription of hypnotics and antalgics was noted. The primary
      outcome measure was the Visual Analogic Scale (VAS) pain means scores in the
      first postoperative 24 hours. RESULTS: There was no difference in the VAS pain
      means scores in the first 24 hours, but it seemed to have a decrease in VAS pain
      at 2 hours in the PB group. Analgesic consumption during surgery was decreased in
      the same group. No complication of the pudendal block has been reported.
      DISCUSSION AND CONCLUSION: The nerve stimulator-guided pudendal nerve block is a
      simple and useful method which can, when associated with general anesthesia,
      reduce per-operative antalgics consumption and a decrease in the immediate
      postoperative pain in perineal or vulvar surgery, without complication or
      lengthening operating time. Further studies are needed to confirm the
      effectiveness of this technique and evaluate the costs and potential
      complications.

PMID- 25618536
TI  - [Age of puberty and western young women sexuality].
AB  - The onset of menarche and age of first sexual experience have both lowered over
      the past century. Does the age of puberty influence the sexuality of the
      girl/young occidental woman? If so, to what degree? Besides, is the acquisition
      of reproductive function, regardless of age, a sign of sufficient maturity to
      engage in sexual activity? Studies show that early puberty, early sex,
      unprotected sexual intercourse in adolescence and number of sexual partners in
      early adulthood are closely related. These early sexual experiences could be
      stimulated by early drug use as well as by depressive disorders. The age of
      puberty has a real influence on sexuality but this link will be modulated by a
      number of social behavioral factors and it is not sustainable. The age of puberty
      is not a good indicator of maturity for teenage sexuality; early maturation and
      early sexual activity are usually associated with risky behaviors. However, other
      studies on the subject are required, including a consideration of the issues
      associated with delayed puberty, a subject virtually absent from the literature. 

PMID- 25618537
TI  - [The four-valve vaginal speculum: a new device to manage post-partum hemorrhage].

PMID- 25618538
TI  - [How I do... extraperitoneal laparoscopy with constant pressure technique].

PMID- 25618539
TI  - Neural network pattern recognition of lingual-palatal pressure for automated
      detection of swallow.
AB  - We describe a novel device and method for real-time measurement of lingual
      palatal pressure and automatic identification of the oral transfer phase of
      deglutition. Clinical measurement of the oral transport phase of swallowing is a
      complicated process requiring either placement of obstructive sensors or sitting
      within a fluoroscope or articulograph for recording. Existing detection
      algorithms distinguish oral events with EMG, sound, and pressure signals from the
      head and neck, but are imprecise and frequently result in false detection. We
      placed seven pressure sensors on a molded mouthpiece fitting over the upper teeth
      and hard palate and recorded pressure during a variety of swallow and non-swallow
      activities. Pressure measures and swallow times from 12 healthy and 7 Parkinson's
      subjects provided training data for a time-delay artificial neural network to
      categorize the recordings as swallow or non-swallow events. User-specific neural
      networks properly categorized 96 % of swallow and non-swallow events, while a
      generalized population-trained network was able to properly categorize 93 % of
      swallow and non-swallow events across all recordings. Lingual-palatal pressure
      signals are sufficient to selectively and specifically recognize the initiation
      of swallowing in healthy and dysphagic patients. 

PMID- 25618540
TI  - A new start from ground zero?
AB  - It is pointed out that one of the main reasons of lack of real conceptual
      progress in the field may lie in the fact that questions concerning the
      biogenesis of macromolecules have never been asked or addressed in a proper way.
      We should start again research on the origin of life starting from "ground zero"
      and focusing on the prebiotic synthesis of ordered sequences of proteins and
      nucleic acids. 

PMID- 25618541
TI  - The problems of replication in the early stages of evolution: enumeration of
      variants and spatial configurations of replicators.
AB  - Two main problems of replication in the early stages of evolution are discussed:
      the problem of exponentially large number of conformational degrees of freedom
      and the problem of enumeration of variants. 

PMID- 25618542
TI  - Erratum to: Papers from EANA 2013.

PMID- 25618543
TI  - The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update.
AB  - Apoptosis is a critically important biological process that plays an essential
      role in cell fate and homeostasis. An important component of the apoptotic
      pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl
      2). The primary role of Bcl-2 family members is the regulation of apoptosis.
      Although the structure of Bcl-2 family of proteins was reported nearly 10 years
      ago, however, it still surprises us with its structural and functional complexity
      and diversity. A number of studies have demonstrated that Bcl-2 family influences
      many other cellular processes beyond apoptosis which are generally independent of
      the regulation of apoptosis, suggesting additional roles for Bcl-2. The
      disruption of the regulation of apoptosis is a causative event in many diseases.
      Since the Bcl-2 family of proteins is the key regulator of apoptosis, the
      abnormalities in its function have been implicated in many diseases including
      cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the
      past few years, our understanding of the mechanism of action of Bcl-2 family of
      proteins and its implications in various pathological conditions has enhanced
      significantly. The focus of this review is to summarize the current knowledge on
      the structure and function of Bcl-2 family of proteins in apoptotic cellular
      processes. A number of drugs have been developed in the past few years that
      target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of
      various diseases and their pharmacological significance as effective molecular
      therapeutic targets is also discussed. 

PMID- 25618544
TI  - Drug-induced liver injury: an overview over the most critical compounds.
AB  - There has been a substantial interest in drug-induced liver injury (DILI)
      recently. National Institutes of Health has sponsored a multicenter study in the
      USA for the last 10 years, which has collected valuable information in this
      context. Idiosyncratic DILI is like other adverse effects of drugs underestimated
      and underreported in most epidemiological studies. A recent prospective
      population-based study from Iceland found a crude incidence of approximately 19
      cases per 100,000 and year. Antibiotic is the class of drugs most commonly
      implicated in patients with DILI. Amoxicillin-clavulanate continues to be the
      most commonly implicated agent occurring in approximately 1 out of 2,300 users.
      Drugs with the highest risk of DILI in the Icelandic study were azathioprine and
      infliximab. Although rare, statin-induced hepatotoxicity has been well
      documented. Liver injury associated with the use of herbal medicines and dietary
      supplements seems to be increasing. Information on the documented hepatotoxicity
      of drugs has recently been made easier by a website available in the public
      domain: LiverTox ( http://livertox.nlm.nih.gov ). Unfortunately, at the current
      time, pre-therapy risk assessment for DILI in the individual patient is difficult
      but previous well-documented hepatotoxicity is usually a contraindication for a
      subsequent treatment with the same drug. 

PMID- 25618545
TI  - The role of DNA damage responses in p53 biology.
AB  - The tumour suppressor p53 is a central player in cellular DNA damage responses.
      P53 is upregulated and activated by genotoxic stress and induces a
      transcriptional programme with effectors promoting apoptosis, cell cycle arrest,
      senescence and DNA repair. For the best part of the last three decades, these DNA
      damage-related programmes triggered by p53 were unequivocally regarded as the
      major if not sole mechanism by which p53 exerts its tumour suppressor function.
      However, this interpretation has been challenged by a number of recent in vivo
      studies, demonstrating that mice which are defective in inducing p53-dependent
      apoptosis, cell cycle arrest and senescence suppress thymic lymphoma as well as
      wild-type p53 expressing animals. Consequently, the importance of DNA damage
      responses for p53-mediated tumour suppression has been questioned. In this
      review, I summarize current knowledge on p53-controlled DNA damage responses and
      argue that these activities, while their role has certainly changed, remain an
      important feature of p53 biology with relevance for cancer therapy and tumour
      suppression. 

PMID- 25618546
TI  - Effect of particle agglomeration in nanotoxicology.
AB  - The emission of engineered nanoparticles (ENPs) into the environment in
      increasing quantity and variety raises a general concern regarding potential
      effects on human health. Compared with soluble substances, ENPs exhibit
      additional dimensions of complexity, that is, they exist not only in various
      sizes, shapes and chemical compositions but also in different degrees of
      agglomeration. The effect of the latter is the topic of this review in which we
      explore and discuss the role of agglomeration on toxicity, including the fate of
      nanomaterials after their release and the biological effects they may induce. In
      depth investigations of the effect of ENP agglomeration on human health are still
      rare, but it may be stated that outside the body ENP agglomeration greatly
      reduces human exposure. After uptake, agglomeration of ENPs reduces translocation
      across primary barriers such as lungs, skin or the gastrointestinal tract,
      preventing exposure of "secondary" organs. In analogy, also cellular ENP uptake
      and intracellular distribution are affected by agglomeration. However,
      agglomeration may represent a risk factor if it occurs after translocation across
      the primary barriers, and ENPs are able to accumulate within the tissue and thus
      reduce clearance efficiency.

PMID- 25618547
TI  - Developmental neurotoxicity of persistent organic pollutants: an update on
      childhood outcome.
AB  - Organohalogens are persistent organic pollutants that have a wide range of
      chemical application. There is growing evidence that several of these chemical
      compounds interfere with human development in various ways. The aim of this
      review is to provide an update on the relationship between various persistent
      organic pollutants and childhood neurodevelopmental outcome from studies from the
      past 10 years. This review focuses on exposure to polychlorinated biphenyls
      (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs) and
      dichlorodiphenyldichloroethylene (DDE), and in addition on exposure to
      phthalates, bisphenol A, and perfluorinated compounds and their associations with
      neurodevelopmental outcome in childhood, up to 18 years of age. This review shows
      that exposure to environmental chemicals affects neurodevelopmental outcome in
      children. Regarding exposure to PCBs and OH-PCBs, most studies report no or
      inverse associations with neurodevelopmental outcomes. Regarding exposure to
      PBDEs, lower mental development, psychomotor development and IQ were found at
      preschool age, and poorer attention at school age. Regarding exposure to DDE,
      most studies reported inverse associations with outcome, while others found no
      associations. Significant relations were particularly found at early infancy on
      psychomotor development, on attention and ADHD, whereas at school age, no adverse
      relationships were described. Additionally, several studies report gender-related
      vulnerability. Future research should focus on the long-term effects of prenatal
      and childhood exposure to these environmental chemicals, on sex-specific and
      combined exposure effects of environmental chemicals, and on possible mechanisms
      by which these chemicals have their effects on neurodevelopmental and behavioral
      outcomes.

PMID- 25618549
TI  - The protozoan Toxoplasma gondii: neurotoxicological relevance beyond the typical
      clinical pictures.

PMID- 25618548
TI  - International STakeholder NETwork (ISTNET): creating a developmental
      neurotoxicity (DNT) testing road map for regulatory purposes.
AB  - A major problem in developmental neurotoxicity (DNT) risk assessment is the lack
      of toxicological hazard information for most compounds. Therefore, new approaches
      are being considered to provide adequate experimental data that allow regulatory
      decisions. This process requires a matching of regulatory needs on the one hand
      and the opportunities provided by new test systems and methods on the other hand.
      Alignment of academically and industrially driven assay development with
      regulatory needs in the field of DNT is a core mission of the International
      STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held
      in Zurich on 23-24 January 2014 in order to explore the concept of adverse
      outcome pathway (AOP) to practical DNT testing. AOPs were considered promising
      tools to promote test systems development according to regulatory needs.
      Moreover, the AOP concept was identified as an important guiding principle to
      assemble predictive integrated testing strategies (ITSs) for DNT. The
      recommendations on a road map towards AOP-based DNT testing is considered a
      stepwise approach, operating initially with incomplete AOPs for compound
      grouping, and focussing on key events of neurodevelopment. Next steps to be
      considered in follow-up activities are the use of case studies to further apply
      the AOP concept in regulatory DNT testing, making use of AOP intersections
      (common key events) for economic development of screening assays, and addressing
      the transition from qualitative descriptions to quantitative network modelling. 

PMID- 25618550
TI  - Long-term and low-dose malathion exposure causes cognitive impairment in adult
      mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and
      apoptotic events.
AB  - The organophosphorus (OP) pesticide malathion is a neurotoxic compound whose
      acute toxicity is primarily caused by the inhibition of acetylcholinesterase
      (AChE), leading to cholinergic syndrome-related symptoms. Some lines of evidence
      indicate that long-term exposure to low levels of OP may produce neuropsychiatric
      and/or neurobehavioral signs that do not necessarily involve the AChE inhibition.
      This study evaluated the effects of a repeated (15-day period) and low-dose
      malathion exposure on spatial memory and discrimination (object location task),
      as well as on biochemical parameters in the hippocampus of mice [AChE and
      mitochondrial chain complexes activities; levels of proapoptotic proteins (Bax
      and Bak) and cholinergic neuronal and astroglial markers (ChAT and GFAP,
      respectively)]. Malathion treatments (30 and 100 mg/kg, s.c.) did not affect the
      body weight of animals and caused no evident signs of cholinergic toxicity
      throughout the treatment, although the highest dose (100 mg/kg) was associated
      with inhibition of AChE activity. Malathion-exposed animals showed a significant
      impairment on spatial memory and discrimination, which was correlated with a
      decrease in the mitochondrial complex I activity in the hippocampus. Moreover,
      malathion increased the levels of proapoptotic proteins and induced astroglial
      activation. The results show that long-term malathion exposure, at a dose that
      does not affect hippocampal AChE activity (30 mg/kg), caused impaired spatial
      memory and discrimination in mice that was related to hippocampal mitochondrial
      dysfunctional, astrogliosis and apoptosis. When extrapolated to humans, such
      results shed light on noncholinergic mechanisms likely related to the
      neurobehavioral and cognitive deficits observed in individuals chronically
      exposed to this pesticide.

PMID- 25618551
TI  - Antioxidant and anti-genotoxic properties of cerium oxide nanoparticles in a
      pulmonary-like cell system.
AB  - Cerium oxide nanoparticles (CeO2-NP) present two different oxidation states what
      can suppose an auto-regenerative redox cycle. Potential applications of CeO2-NP
      to quench reactive oxygen species (ROS) in biological systems are currently being
      investigated. In this context, CeO2-NP may represent a novel agent to protect
      cells and tissues against oxidative damage by its regenerative free radical
      scavenging properties. In this study, we have used a human epithelial lung cell
      line, BEAS-2B, as a model to study the possible antioxidant and anti-genotoxic
      effect of CeO2-NP in a pulmonary-like system. We have assessed the protective
      effect of CeO2-NP pre-treatment in front of a well-defined oxidative stress
      inducing agent (KBrO3). Different endpoints like toxicity, intracellular ROS
      induction, genotoxicity and DNA oxidative damage (comet assay), and gene
      expression alterations have been evaluated. The obtained results confirmed the
      antioxidant properties of CeO2-NP. Thus, its pre-treatment significantly reduced
      the intracellular production of ROS induced by KBrO3. Similarly, a reduction in
      the levels of DNA oxidative damage, as measured with the comet assay complemented
      with formamidopyrimidine DNA glycosylase enzyme, was also observed. Pre-treatment
      of BEAS-2B cells with CeO2-NP (at 2.5 ug/mL) slightly increased the viability of
      cells treated with KBrO3 as well as down-regulated the expression of the Ho1 and
      Sod2 genes involved in the oxidative Nrf2 pathway. Our finding would support the
      potential usefulness of CeO2-NP as a pharmacological agent to be used against
      diseases caused by oxidative stress. 

PMID- 25618552
TI  - Kindlin-2: a novel prognostic biomarker for patients with hepatocellular
      carcinoma.
AB  - The association of aberrant expression of Kindlin-2 with tumor progression has
      been reported in recent years. The purpose of this study was to investigate the
      expression of Kindlin-2 in hepatocellular carcinoma (HCC), and to evaluate its
      clinical and prognostic significance. The mRNA and protein levels of Kindlin-2 in
      HCC and adjacent non-cancerous tissues were examined by real-time PCR and western
      blotting. The relationships between Kindlin-2 expression, clinicopathological
      features and postoperative survival of HCC patients were also evaluated. Kindlin
      2 expression was higher in HCC tissues as compared to adjacent non-cancerous
      tissues at both mRNA and protein levels (P<0.05, respectively). Positive
      expression of Kindlin-2 was significantly correlated with larger tumor size
      (P=0.034), capsular invasion (P=0.009), microvascular invasion (P=0.028) and poor
      prognosis of HCC patients (P<0.001). Moreover, multivariate survival analysis
      identified Kindlin-2 as an independent prognostic factor for overall and disease
      free survival of HCC patients (P=0.018 and 0.001, respectively). Taken together,
      our findings suggested that Kindlin-2 was highly expressed in HCC tissues and was
      closely related to clinical progression. Therefore, Kindlin-2 protein could be a
      potential biomarker for predicting poor prognosis of HCC patients after surgery. 

PMID- 25618553
TI  - Orofacial granulomatosis in children: think about Crohn's disease.
AB  - BACKGROUND: The term orofacial granulomatosis is conventionally used to describe
      patients with granulomatous lesions affecting the orofacial tissues, in absence
      of intestinal lesions. Lip swelling and facial swelling are the most common
      clinical signs. Despite the fact that histologically it is not distinguishable
      from Crohn's disease, and that both diseases have a chronic/recurrent course, the
      relationship between orofacial granulomatosis and Crohn's disease is still
      debated. METHODS: Herein we present five cases of orofacial granulomatosis.
      RESULTS: All patients presented concomitant Crohn's disease, supporting the
      hypothesis that orofacial granulomatosis and Crohn's disease may be one single
      disease. Thalidomide was effective in inducing remission of oral and intestinal
      symptoms in all five cases and could be considered a valid treatment opportunity
      for these patients. CONCLUSIONS: Orofacial granulomatosis and Crohn's disease may
      be part of the same disease; both may respond to thalidomide.

PMID- 25618554
TI  - Sarcopenia is a risk factor for elevated aminotransferase in men independently of
      body mass index, dietary habits, and physical activity.
AB  - BACKGROUND: Aminotransferase activity is a surrogate marker of liver injury
      showing strong correlations with obesity and metabolic syndrome. However,
      elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic
      patients in clinical practice. AIM: To examine the relationship between
      sarcopenia and aminotransferase activity in a large population-based cohort.
      METHODS: Data from the Korean National Health and Nutrition Examinations were
      used. A total of 13,431 subjects were included. A whole-body dual X-ray
      absorptiometry scan was performed on each patient to measure total and regional
      muscle mass. Appendicular skeletal muscle mass indices were also obtained.
      RESULTS: The prevalence of sarcopenia was significantly higher in the group with
      elevated aminotransferase levels than in the normal liver enzyme group (males:
      26.5% vs. 16.9%; females: 38.3% vs. 22.1%, p<0.05). The skeletal muscle index was
      negatively correlated with most cardiometabolic risk factors, including fasting
      glucose and cholesterol levels. The frequency of elevated aminotransferase
      increased in male patients with sarcopenia after adjusting for potential
      confounding factors including age, body mass index, fasting glucose level,
      dietary, and exercise habits. However, the correlation was no longer observed in
      women after adjusting for body mass index. CONCLUSION: Sarcopenia is a risk
      factor for elevated aminotransferase in men, independently of body mass index,
      dietary habits, and physical activity.

PMID- 25618555
TI  - Malnutrition assessed through phase angle and its relation to prognosis in
      patients with compensated liver cirrhosis: a prospective cohort study.
AB  - BACKGROUND: Malnutrition is a frequent complication of cirrhosis and it has been
      associated to more severe disease and development of complications. Phase angle
      is a bedside reliable tool for nutritional assessment based on conductivity
      properties of body tissues. AIM: To evaluate the association between malnutrition
      assessed through phase angle and mortality in patients with liver cirrhosis.
      METHODS: We performed a prospective cohort study in a tertiary care centre; 249
      patients were enrolled with 48 months of follow-up. Clinical, nutritional
      (malnutrition = phase angle <= 4.9 degrees ) and biochemical evaluations were
      performed. Student's t-test and chi(2) method were used as appropriate. Kaplan
      Meier curves and multivariate Cox regression were used to evaluate mortality.
      RESULTS: Mean follow-up was 33.5 months. Survival analysis showed higher
      mortality in the malnourished group compared to the well-nourished group (p =
      0.076), Kaplan-Meier curves were further stratified according to compensated and
      decompensated status showing higher mortality in compensated patients according
      to Child-Pugh (p = 0.002) and Model for End-Stage Liver Disease score (p = 0.008)
      when malnutrition was present. Multivariate analysis showed that malnutrition was
      independently associated with mortality (HR = 2.15, 1.18-3.92). CONCLUSIONS: In
      our cohort, malnutrition was independently associated with mortality. This is the
      first study showing higher mortality in malnourished compensated cirrhotic
      patients.

PMID- 25618556
TI  - Gastric pseudopolyposis formed after recovery from gastric gangrene.

PMID- 25618557
TI  - Early Revisit to the Emergency Department: An Integrative Review.

PMID- 25618558
TI  - A perivesical mass in a 79-year-old with a treated adenocarcinoma of the
      prostate.

PMID- 25618559
TI  - Patients with urinary bladder paragangliomas: a compiled case series from a
      literature review for clinical management.

PMID- 25618560
TI  - Neuroprotective effects of intravitreally transplanted adipose tissue and bone
      marrow-derived mesenchymal stem cells in an experimental ocular hypertension
      model.
AB  - BACKGROUND AIMS: The purpose of this study was to investigate the neuroprotective
      effects of bone marrow bone marrow-derived and adipose tissue-derived mesenchymal
      stromal cells (MSCs) that were intravitreally transplanted in an experimental
      ocular hypertension (OHT) model. METHODS: An OHT rat model was generated by means
      of intracameral injection of hyaluronic acid into the anterior chamber. MSCs
      labeled with green fluorescence protein were transplanted intravitreally 1 week
      after OHT induction. At the end of the second and fourth weeks, retinal ganglion
      cells were visualized with the use of a flat-mount retina method and were
      evaluated by means of immunofluorescence staining against green fluorescence
      protein, vimentin, CD105, and cytokines (interleukin [IL]-1Ra, prostaglandin E2
      receptor, IL-6, transforming growth factor-beta1, interferon-gamma and tumor
      necrosis factor-alpha). RESULTS: The retinal ganglion cell numbers per area were
      significantly improved in stem cell-treated OHT groups compared with that in the
      non-treated OHT group (P < 0.05). The results of immunohistochemical analyses
      indicated that a limited number of stem cells had integrated into the ganglion
      cell layer and the inner nuclear layer. The number of cells expressing
      proinflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha)
      decreased in the MSC-transferred group compared with that in the OHT group after
      4 weeks (P < 0.01). On the other hand, IL-1Ra and prostaglandin E2 receptor
      expressions were increased in the rat bone marrow-derived MSC group but were more
      significant in the rat adipose tissue-derived MSC group (P < 0.01). CONCLUSIONS:
      After intravitreal transplantation, MSCs showed a neuroprotective effect in the
      rat OHT model. Therefore, MSCs promise an alternative therapy approach for
      functional recovery in the treatment of glaucoma.

PMID- 25618561
TI  - Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase
      expressing umbilical cord mesenchymal stromal cells.
AB  - BACKGROUND AIMS: Acute radiation syndrome (ARS) leads to pancytopenia and multi
      organ failure. Transplantation of hematopoietic stem cells provides a curative
      option for radiation-induced aplasia, but this therapy is limited by donor
      availability. METHODS: We examined an alternative therapeutic approach to ARS
      with the use of human extracellular superoxide dismutase (ECSOD)-modified
      umbilical cord mesenchymal stromal cells (UCMSCs). This treatment combines the
      unique regenerative role of UCMSCs with the anti-oxidative activity of ECSOD.
      RESULTS: We demonstrated that systemically administered ECSOD-UCMSCs are able to
      protect mice from sub-lethal doses of radiation and improve survival by promoting
      multilineage hematopoietic recovery. The therapeutic effect of this treatment is
      related to the decrease in radiation-induced O(2)(-) and apoptosis. CONCLUSIONS:
      Our data highlight the clinical potential of this two-pronged approach to the
      treatment of ARS, thereby serving as a rapid and effective first-line strategy to
      combat the hematopoietic failure resulting from a radiation accident, nuclear
      terrorism and other radiologic emergencies.

PMID- 25618562
TI  - Effective gene delivery into adipose-derived stem cells: transfection of cells in
      suspension with the use of a nuclear localization signal peptide-conjugated
      polyethylenimine.
AB  - BACKGROUND AIMS: Adipose-derived stem cells have the ability to turn into several
      clinically important cell types. However, it is difficult to transfect these
      cells with the use of conventional cationic lipid-based reagents.
      Polyethylenimine (PEI) is considered to be an inexpensive and effective tool for
      delivery of nucleic acids into mammalian cells. METHODS: We used a linear PEI
      conjugated with the nuclear localization signal (NLS) peptide of Simian
      vacuolating virus 40 large T antigen (PEI-NLS) for transfection of plasmid DNA
      into adipose-derived cells. We also tested if transfection of cells in suspension
      might improve the degree and duration of exogenous gene expression. RESULTS:
      Transfection of cells in suspension with the use of a PEI conjugated with an NLS
      peptide resulted in high levels of reporter gene expression for an extended
      period of time in clonal 3T3-L1 preadipocytes and native human adipose-derived
      stem cells. The reporter gene expression increased for 3 days after the addition
      of the PEI-NLS peptide-DNA mixture in cell suspension and remained significant
      for at least 7 days. Cell density did not influence the level of reporter gene
      expression. Thus, the suspension method with the use of an NLS peptide-conjugated
      PEI leads to a robust and sustained expression of exogenous genes in adipose
      derived cells. CONCLUSIONS: The devised transfection method may be useful for
      reprogramming of adipose-derived stem cells and cell-based therapy.

PMID- 25618563
TI  - Leptin Reference Values and Cutoffs for Identifying Cardiometabolic Abnormalities
      in the Spanish Population.
AB  - INTRODUCTION AND OBJECTIVES: Estimate leptin reference values and calculate
      leptinemia cutoff values for identifying cardiometabolic abnormalities in Spain.
      METHODS: Cross-sectional study carried out between 2008 and 2010 in 11 540
      individuals representing the Spanish population aged >= 18 years. Data were
      obtained by standardized physical examination and analyses were performed at a
      central laboratory. Leptinemia was measured using ELISA. Cardiometabolic
      abnormality was defined as the presence of at least two of the following: high
      blood pressure, high triglycerides, reduced high density lipoprotein cholesterol,
      high insulin resistance values, and elevated C-reactive protein and glucose.
      RESULTS: Leptin values were higher in women than men (geometric mean, 21.9 and
      6.6 ng/mL; P<.001). The median [interquartile range] was 24.5 [14.1-37.0] ng/mL
      in women, and 7.2 [3.3-14.3] ng/mL in men. In the multivariate analysis, leptin
      was significantly associated with anthropometric measures, insulin, and C
      reactive protein, and inversely associated with age, smoking, and physical
      activity in women (r(2)=0.53; P<.001) and in men (r(2)=0.61; P<.001). The leptin
      values that identified cardiometabolic abnormality were 23.75 ng/mL in women
      (area under the curve, 0.722; sensitivity, 72.3%; specificity, 58.7%) and 6.45
      ng/mL in men (area under the curve, 0.716; sensitivity, 71.4%; specificity,
      60.2%). CONCLUSIONS: These results facilitate the interpretation of leptin values
      in clinical and population studies. Leptin has moderate sensitivity and
      specificity for identifying cardiometabolic abnormalities.

PMID- 25618564
TI  - Regeneration, relocation and health behaviours in deprived communities.
AB  - In the UK, recent regeneration programmes have aimed to improve the health of
      those who remain in their neighbourhood (Remainers) and those who are relocated
      (Outmovers); thus, as part of the 10-year GoWell study (2006-2015) of the effects
      of demolition, rebuilding and housing improvements on residents and communities,
      we examined associations of health behaviours with residential conditions and
      location status in deprived neighbourhoods of Glasgow. Better internal dwelling
      conditions were associated with several better health behaviours; in relation to
      neighbourhood conditions, the results were more mixed. Outmovers often exhibited
      worse health behaviours than Remainers, perhaps because environmental and social
      conditions were little altered by relocation, and because personal support
      mechanisms were missing. Health behaviours were relatively good among Remainers,
      indicating that in situ changes might stimulate life-changing improvements, but
      relocation less so. 

PMID- 25618565
TI  - Exposure to neighborhood immigrant concentration from adolescence to young
      adulthood and immune function among Latino young adults.
AB  - The immune system plays a critical role in the prevention of infectious and
      chronic disease. We investigate associations between exposure to neighborhood
      immigrant concentration across the transition from adolescence to adulthood and
      immune function among Latino young adults, including moderation by nativity. Data
      from the National Longitudinal Study of Adolescent Health (1994-2008) were
      analyzed. Immune function was measured via Epstein-Barr virus (EBV) antibody
      levels (higher levels indicate impaired immune function) among EBV-positive
      Latino adults (N=1130). Results indicated the averaged individual exposure to
      immigrant concentration (mean % of foreign-born residents in the census tract
      across waves 1-4) was associated with immune function for foreign-born Latinos
      only (b=-0.37, P<0.05). For waves of exposure, only the cumulative measure of
      living in an immigrant enclave (census tracts with >=40% foreign-born residents)
      across all waves was associated with immune function and only for foreign-born
      Latinos (b=-0.22, P<0.05). Research on the mechanisms through which neighborhood
      immigrant concentration confers salubrious physiological outcomes for foreign
      born Latinos is needed. 

PMID- 25618566
TI  - Effect of transcranial direct current stimulation (tDCS) on MMN-indexed auditory
      discrimination: a pilot study.
AB  - Membrane potentials and brain plasticity are basic modes of cerebral information
      processing. Both can be externally (non-invasively) modulated by weak
      transcranial direct current stimulation (tDCS). Polarity-dependent tDCS-induced
      reversible circumscribed increases and decreases in cortical excitability and
      functional changes have been observed following stimulation of motor and visual
      cortices but relatively little research has been conducted with respect to the
      auditory cortex. The aim of this pilot study was to examine the effects of tDCS
      on auditory sensory discrimination in healthy participants (N = 12) assessed with
      the mismatch negativity (MMN) brain event-related potential (ERP). In a
      randomized, double-blind, sham-controlled design, participants received anodal
      tDCS over the primary auditory cortex (2 mA for 20 min) in one session and 'sham'
      stimulation (i.e., no stimulation except initial ramp-up for 30 s) in the other
      session. MMN elicited by changes in auditory pitch was found to be enhanced after
      receiving anodal tDCS compared to 'sham' stimulation, with the effects being
      evidenced in individuals with relatively reduced (vs. increased) baseline
      amplitudes and with relatively small (vs. large) pitch deviants. Additional
      studies are needed to further explore relationships between tDCS-related
      parameters, auditory stimulus features and individual differences prior to
      assessing the utility of this tool for treating auditory processing deficits in
      psychiatric and/or neurological disorders.

PMID- 25618567
TI  - Dispersive liquid-liquid microextraction of lead(II) as 5-(4
      dimethylaminobenzylidene) rhodanine chelates from food and water samples.
AB  - A dispersive liquid-liquid microextraction procedure for lead(II) as its 5-(4
      dimethylaminobenzylidene) rhodanine complex has been established prior to its
      microsampling flame atomic absorption spectrometric determination. The influences
      of various analytical parameters including pH, solvent type and volume,
      dispersive solvent type and volume, 5-(4-dimethylaminobenzylidene) rhodanine
      amount, salt effect, and centrifugation time and speed were investigated. The
      effects of certain alkali, alkaline earth, and transition metal ions on the
      quantitative extraction of lead(II) were also studied. Quantitative recoveries
      were obtained at pH 6. The enrichment factor was calculated as 125. The detection
      limit for lead is 1.1 MUg/L. The accuracy of the method was tested with the
      additions recovery test and analysis of the standard reference materials (SPS-WW2
      waste water, NIST SRM 1515 apple leaves, and TMDA-51.3 fortified water).
      Applications of the present procedure were tested by analyzing water and food
      samples.

PMID- 25618568
TI  - Correlation of aluminum and manganese concentration in scalp hair samples of
      patients having neurological disorders.
AB  - Neurodegenerative diseases are thought to be multifactorial, while metals
      (aluminum and manganese) can be involved as cofactors in abnormalities or
      suspected of being risk factors for this disorder. The aim of our study was to
      assess the aluminum (Al) and manganese (Mn) concentrations in scalp hair samples
      of 397 patients having different types of neurological disorder diseases. For
      comparative purpose, scalp hair samples of 201 control subjects does not have any
      neuro-disorders of same age group (30-60 years) and were selected as referents.
      The Al and Mn in scalp hair samples were assessed by the electrothermal atomic
      absorption spectrophotometry after microwave-assisted acid digestion. The
      validity of methodology was checked by the certified human hair reference
      material (NCS ZC81002). The results of this study showed that the mean values of
      Al and Mn were significantly higher in scalp hair samples of all types of
      neurological disorder patients as compared to controls (p = 0.01-0.001). The high
      levels of Al and Mn may play a role in the development of neurological disorders.
      However, further work is suggested to examine the precise correlation between
      trace elemental level and the degree of disorders in neurological patients.

PMID- 25618569
TI  - Study of the Interaction of 1,4- and 1,5-Benzodiazepines with GABAA Receptors of
      Rat Cerebellum Granule Cells in Culture.
AB  - The effects of a classical 1,4-benzodiazepine agonist, such as diazepam, its
      catabolite N-desmethyl-diazepam (nordiazepam), and 1,5-benzodiazepines such as
      clobazam and RL 214 (a triazolobenzodiazepine previously synthesized in our labs)
      were evaluated on native GABAA receptors of cerebellar granule cells in culture.
      The parameter studied was the increase of GABA-activated chloride currents caused
      by these substances. The contributions of alpha6 beta2/3 gamma2 and alpha1 alpha6
      beta2/3 gamma2 receptor subtypes to the increase of GABA-activated chloride
      current were investigated by comparing the effects of such substances in the
      presence vs. the absence of furosemide. Furosemide is in fact able to block such
      receptors. It was found that the percent enhancement of peak GABA-activated
      current doubled for diazepam, clobazam, and RL 214. However, it did not change
      for N-desmethyl-diazepam. These results indicate that diazepam, clobazam, and RL
      214 interact exclusively with alpha1 beta2/3 gamma2 receptors, while N-desmethyl
      diazepam seems to interact with not only alpha1- but also alpha6-containing
      receptors. 

PMID- 25618570
TI  - Childhood extravasation injuries: improved outcome following the introduction of
      hospital-wide guidelines.
AB  - INTRODUCTION: Extravasation is an iatrogenic injury that may produce soft tissue
      necrosis requiring surgical reconstruction (Rose et al., 2008) and (Goon et al.,
      2006). Previous review of extravasation injuries within our hospital showed that
      early referral to plastic surgeons and washout of high-risk cases lead to
      favourable outcome in 86% of patients (Gault, 1993). Hospital-wide guidelines
      were introduced in 2005. This paper closes the audit loop by evaluating
      extravasation injuries outcome following the introduction of these guidelines.
      METHODS: All patients referred to the plastic surgery department for
      extravasation injuries between October 2008 and October 2009 were reviewed. A
      favourable outcome was defined as resolution without tissue loss requiring
      surgical reconstruction. Patients were excluded if they sustained the
      extravasation in other institution. RESULTS: A total of 82 extravasation injuries
      in 78 patients were reviewed during the audit period. Mean age was 3.2 years
      (Median 0.2 years, Minimum 0 day, and maximum 16.7 years). The injuries were more
      frequent on the left half of the body (52%) and involving the upper limbs (59%).
      Mean time to referral was 8 h, with 60% of patients referred within 6 h of the
      injury, 30% in 6-12 h, and 10% referred after more than 12 h 26% of the injuries
      required washout treatment - the rest was treated conservatively. Tissue necrosis
      occurred in 3 cases (4%) but required no surgical intervention due to the small
      area affected. CONCLUSION: Our audit showed an improved outcome of extravasation
      injury following introduction of hospital-wide guidelines of early referral to
      specialist team and washout of high-risk cases.

PMID- 25618571
TI  - Rheumatic symptoms in autoimmune thyroiditis.
AB  - Autoimmune thyroiditis (ATD) is generally regarded as a classic example of single
      organ autoimmunity with a high association with endocrine thyroid disorders.
      However, it is closely associated with several autoimmune diseases including
      rheumatologic syndromes and has long been known to have several rheumatic
      manifestations particularly in association with hypothyroidism. More recently, it
      has also been implicated in rheumatologic syndromes in the absence of
      hypothyroidism or subclinical hypothyroidism. There is also an emerging body of
      evidence that ATD is highly linked to chronic generalized pain syndromes
      including fibromyalgia. This review examines the rheumatic symptoms of ATD
      described in the current literature and discusses the clinical relevance of ATD
      in general rheumatology. 

PMID- 25618572
TI  - Giant cell arteritis and polymyalgia rheumatica: an update.
AB  - Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely
      related diseases in people aged 50 years and older, which are more frequently
      observed in Western countries. Despite being common entities, concern still
      exists about the epidemiology, pathogenesis, and diagnosis of both entities. New
      imaging techniques, such as 18 fluorodeoxyglucose-positron emission tomography,
      have proved to be useful in detecting large-vessel involvement in GCA.
      Corticosteroids are the cornerstone of the therapy in GCA and PMR. Relapses are
      frequent in these conditions. Unlike methotrexate and tumor necrosis factor-alpha
      antagonists, anti-interleukin-6 receptor therapy appears to be useful in patients
      with GCA and PMR who are refractory to corticosteroids. This review summarizes
      recent studies on GCA and PMR. 

PMID- 25618573
TI  - The challenge of bleeding in antiphospholipid antibody-positive patients.
AB  - Antiphospholipid antibody-positive patients can develop bleeding due to
      capillaritis, microthrombosis, antiprothrombin antibodies, thrombocytopenia,
      and/or excessive antithrombotic therapy. Clinical characteristics of patients,
      e.g., renal impairment, elderly, or concomitant medications, are closely related
      to the risk of bleeding. The management of bleeding in antiphospholipid antibody
      (aPL)-positive patients is challenging due to the baseline increased risk of
      thrombosis. If anticoagulation is stopped, it should be restarted as soon as
      possible once the acute bleeding is controlled; the continuation of
      anticoagulation despite active bleeding may be required in selected cases. High
      dose corticosteroid is the mainstay treatment for diffuse alveolar hemorrhage,
      lupus anticoagulant-hypoprothrombinemia syndrome, and severe thrombocytopenia;
      immunosuppressive drugs are also required to improve the long-term outcomes.
      Hydrocortisone is critical in adrenal hemorrhage patients due to concomitant
      adrenal insufficiency; despite bleeding, anticoagulation should be maintained as
      much as possible. Plasma exchange should be considered in catastrophic
      antiphospholipid syndrome patients with concurrent bleeding. This article will
      review the causes of bleeding in aPL-positive patients as well as the management
      strategies. 

PMID- 25618574
TI  - Biosimilars: clinical interpretation and implications for drug development.
AB  - The European Medicines Agency's recent approval of biosimilars and their sudden
      appearance on the market will revolutionize the way physicians treat the severe
      conditions for which biologics have had a major impact. In the field of
      rheumatology, these agents are especially important because most new treatments
      are based on this kind of medication and because patents on the original drugs
      are expiring. To use these new medications, the treating physician must read and
      understand the clinical trials related to biosimilars. These studies are not the
      typical superiority trials in which new agents are compared with standard
      treatment; rather, they evaluate different formulas to determine whether they are
      no better or worse. This article summarizes the clinical aspects of drug
      development with regard to the efficacy and safety of these new medications. 

PMID- 25618575
TI  - Development of the headache activities of daily living index: initial validity
      study.
AB  - PURPOSE: The purpose of this study was to develop a novel instrument for
      assessing headache-related disability focusing solely on important activities of
      daily living. METHODS: Part 1: A literature search was conducted in PubMed and
      Google Scholar, supplemented by hand searches in bibliographies to retrieve the
      original article for any instrument for the assessment of headache-related
      disability. Each instrument was evaluated for item categories, specific item
      content, measurement scale format for each item, and instructions to users.
      Together, these features constituted the construct validity of these instruments.
      Qualitative evaluations of these results were summarized with respect to the
      adequacy of each component. Psychometric features such as reliability and
      validity were not assessed. Part 2: An existing instrument for assessing self
      rated disability, the Neck Disability Index, was modified for content and format
      and subjected to 2 rounds of clinician and patient review. Item contents and
      formats received final consensus, resulting in a 9-item instrument: the Headache
      Activities of Daily Living Index (HADLI). This instrument was tested in a sample
      of headache patients. Cronbach alpha and individual item correlations were
      obtained. Principal Components Analysis was performed. RESULTS: Part 1: The
      search identified 6 reports on 5 preexisting instruments for self-rating of
      headache-related disability. Problems in content were found in all instruments,
      especially relating to the lack of items for specific activities of daily living.
      Problems were noted in most of the instruments for scaling and instructions with
      respect to the effect of headache on activities of daily living. Part 2: The
      authors first identified suitable items from an existing instrument for self
      rating of disability. These were supplemented by items drawn from the literature.
      A panel of 3 clinicians and 2 laypersons evaluated these items. Two more focus
      groups of 7 headache sufferers each reviewed the new instrument. After this, a 9
      item instrument for assessing activities of daily living in headache sufferers,
      the HADLI, was finalized. After this, 53 participants were recruited to study the
      face validity of the instrument. The sample consisted of 41 women and 12 men with
      a mean age of 37.3 (12) years; mean duration of headaches was 7.4 (8.3) years;
      mean frequency of headaches per week was 3.4 (2.4); and the intensity was 6
      (2.4). The mean HADLI score was 26.2 (13.4), or 52%. There were no floor or
      ceiling effects for total score. The total Index Cronbach alpha was 0.96. The
      Principal Components Analysis identified one component which accounted for 75% of
      the variance. CONCLUSIONS: The HADLI was created using theory and empirical-based
      methods. Face validity was assessed by focus group input and by first-level
      psychometrics. The HADLI has good face validity and is suitable for further
      reliability and validity testing.

PMID- 25618576
TI  - Acute bilateral mass-occupying lesions in non-penetrating traumatic brain injury:
      a retrospective study.
AB  - BACKGROUND: Traumatic acute bilateral mass-occupying lesions (TABML) is a common
      entity in head injury, with high morbidity and mortality. Our aim in this study
      was to evaluate the benefits of different treatment options and the outcome
      predictors in patients with TABML. METHODS: From October 2010 to November 2012, a
      consecutive cohort of patients aged 16-70 years with TABML were retrospectively
      analyzed based on the clinical and radiological characteristics. Patients with
      TABML were included if admitted within 24 h after injury and were excluded if
      they presented with infratentorial lesions, unilateral lesions within the first
      24 h after injury, or penetrating head injury. According to their treatment
      option, patients were divided into three groups: a conservative treatment group,
      a unilateral surgery group, and a bilateral surgery group. Outcomes were assessed
      using the Glasgow Outcome Scale (GOS). Binary logistic regression analysis was
      applied to determine the outcome predictors. RESULTS: Forty-seven patients
      (58.8%) had severe injuries (Glasgow Coma Scale score (GCS), 3-8) upon admission,
      and the overall mortality was 31.3% at 6 months post-injury. The mortality was
      55.6% in patients who underwent conservative treatment (N = 18), 17.9% in
      unilateral surgery patients (N = 39), and 34.8% in the bilateral surgery group (N
      = 23). In the surgical group, the mortality was 53.3% (8 of 15) in those with a
      GCS of 3-5, which decreased steeply to 14.9% (7 of 47) of those with GCS >= 6. On
      logistic regression analysis, the absence of pupillary reactivity, disappearances
      of basal cisterns and conservative treatment were related to higher mortality. A
      lower initial GCS score was associated with an unfavorable outcome. Midline shift
      tended to be associated with mortality and an unfavorable outcome, although
      statistical analysis did not show a significant difference. CONCLUSIONS: TABML is
      suggestive of severe brain injury. As conservative treatment is always associated
      with a poorer outcome, surgery is advocated, especially in patients with a GCS
      score of >= 6. Whereas the prognostic value of midline shift might be limited
      because of the counter-mass effect in TABML, the GCS score, the pupillary
      reactivity, and particularly, the compression of basal cisterns should be
      emphasized.

PMID- 25618578
TI  - Recreational Drowning Prevention Interventions for Adults, 1990-2012: A Review.
AB  - Drowning is a frequently occurring and preventable public health issue.
      Internationally, drowning literature has focussed on children under 5 years,
      however, evidence based interventions to prevent adult drowning are needed to
      reduce deaths on a global scale. The aim of this paper is to systematically
      identify and analyse the evidence for drowning interventions with an adult focus.
      A systematic search was undertaken for peer-reviewed articles which were
      published in English between 1990 and 2012, focused on adults and described a
      drowning intervention. After quality appraisal by expert reviewers using a
      purposively tailored checklist, a final total of six studies were included for
      review. The six studies were all conducted in high income countries. Four were
      drowning interventions, two were retrospective analyses. The drowning
      interventions duration ranged from 10 days to 5 years, the analysis studies from
      6 to 21 years. Two of the studies reviewed used behaviour change theory to inform
      development, and two reported formative evaluation. Prevention strategies
      included education (n = 3), technology (n = 1) and environmental (n = 1).
      Positive short term effects and significant behaviour change in life jacket use
      was reported (n = 2). A mixed effect was observed in the six studies. The
      complexity of the issues surrounding drowning requires the collection of robust
      data and evaluation of preventative measures to support the development of
      targeted and tailored prevention interventions. This review reinforces the need
      for a genuine and sustained global approach to addressing adult drowning
      prevention. Drowning is a serious public health issue and should receive the same
      attention as other public health priorities .

PMID- 25618577
TI  - Assessment of coronary atherosclerosis in patients with familial
      hypercholesterolemia by coronary computed tomography angiography.
AB  - The aims of this study were (1) to determine whether the accumulation of coronary
      plaque burden assessed with coronary computed tomography angiography (CCTA) can
      predict future events and (2) to estimate the onset and progression of coronary
      atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive
      101 Japanese patients with heterozygous FH (men = 52, mean age 56 +/- 16 years,
      mean low-density lipoprotein cholesterol 264 +/- 58 mg/dl) who underwent 64
      detector row CCTA without known coronary artery disease were retrospectively
      evaluated by assigning a score (0 to 5) to each of 17 coronary artery segments
      according to the Society of Cardiovascular Computed Tomography guidelines. Those
      scores were summed and subsequently natural log transformed. The periods to major
      adverse cardiac events (MACE) were estimated using multivariable Cox proportional
      hazards models. During the follow-up period (median 941 days), 21 MACE had
      occurred. Receiver operating characteristic curve analyses identified a plaque
      burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a
      worse prognosis. Multivariate Cox regression analysis identified the presence of
      a plaque score >=3.35 as a significant independent predictor of MACE (hazard
      ratio = 3.65; 95% confidence interval 1.32 to 25.84, p <0.05). The regression
      equations were Y = 0.68X - 15.6 (r = 0.54, p <0.05) in male and Y = 0.74X - 24.8
      (r = 0.69, p <0.05) in female patients with heterozygous FH. In conclusion,
      coronary plaque burden identified in a noninvasive, quantitative manner was
      significantly associated with future coronary events in Japanese patients with
      heterozygous FH and that coronary atherosclerosis may start to develop, on
      average, at age 23 and 34 years in male and female patients with heterozygous FH,
      respectively.

PMID- 25618579
TI  - Comparison of hospitalization among German coastal and deep sea fishermen.
AB  - PURPOSE: This study aims to compare the hospitalization of German fishermen
      employed on German-flagged fishing vessels with that of the general German
      population in consideration of differences between coastal and deep sea fishery.
      METHODS: By means of a database from the health insurance company for seafarers,
      diagnoses of German fishermen treated in German hospitals were determined from
      January 1997 to December 2007. Compared with the general German population, the
      fishermen's risk for specific diseases leading to hospitalization was calculated
      as standardized hospitalization ratio (SHR). RESULTS: Compared with the German
      reference population, German fishermen showed a considerably high SHR for
      malignant neoplasms at all sites (SHR 1.46; 95% CI 1.37-1.56), for respiratory
      cancer, and for non-Hodgkin lymphoma (NHL). Furthermore, they had more often been
      hospitalized due to diabetes mellitus, diseases of the respiratory and digestive
      systems as well as due to injury and poisoning. The risk for respiratory cancer
      and NHL among coastal fishermen exceeded that of deep sea fishermen, whereas the
      latter displayed a considerably higher SHR for diabetes mellitus, diseases of the
      respiratory system and metabolic and nutritional disorders. In contrast, the SHR
      for hypertensive and ischemic heart diseases was decreased among deep sea
      fishermen. Less qualified deep sea fishermen displayed a considerably higher SHR
      for malignant neoplasms at all sites than more highly qualified ones.
      CONCLUSIONS: Fishery is still an occupation which poses a high risk for malignant
      neoplasms and injuries. This is likely due to lifestyle and work-related factors.
      Further studies are needed to evaluate the different working and living
      conditions of coastal and deep sea fishermen.

PMID- 25618580
TI  - Possible involvement of membrane lipids peroxidation and oxidation of
      catalytically essential thiols of the cerebral transmembrane sodium pump as
      component mechanisms of iron-mediated oxidative stress-linked dysfunction of the
      pump's activity.
AB  - The precise molecular events defining the complex role of oxidative stress in the
      inactivation of the cerebral sodium pump in radical-induced neurodegenerative
      diseases is yet to be fully clarified and thus still open. Herein we investigated
      the modulation of the activity of the cerebral transmembrane electrogenic enzyme
      in Fe(2+)-mediated in vitro oxidative stress model. The results show that Fe(2+)
      inhibited the transmembrane enzyme in a concentration dependent manner and this
      effect was accompanied by a biphasic generation of aldehydic product of lipid
      peroxidation. While dithiothreitol prevented both Fe(2+) inhibitory effect on the
      pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not
      inhibition of the pump. Besides, malondialdehyde (MDA) inhibited the pump by a
      mechanism not related to oxidation of its critical thiols. Apparently, the low
      activity of the pump in degenerative diseases mediated by Fe(2+) may involve
      complex multi-component mechanisms which may partly involve an initial oxidation
      of the critical thiols of the enzyme directly mediated by Fe(2+) and during
      severe progression of such diseases; aldehydic products of lipid peroxidation
      such as MDA may further exacerbate this inhibitory effect by a mechanism that is
      likely not related to the oxidation of the catalytically essential thiols of the
      ouabain-sensitive cerebral electrogenic pump. 

PMID- 25618583
TI  - Incidence of severe combined immunodeficiency through newborn screening in a
      Chinese population.
AB  - BACKGROUND/PURPOSE: In order to know the true incidence of severe combined
      immunodeficiency (SCID) in a Chinese population, we conducted and implemented
      SCID newborn screening in Taiwan. METHODS: Between May 1, 2010 and December 31,
      2011, the National Taiwan University Hospital Newborn Screening Center screened
      all newborns for T-cell lymphopenia by measuring the copy number of T-cell
      receptor excision circles (TRECs) and RNase P. Newborns with low TREC values were
      subjected to complete blood cell counts and flow cytometry. RESULTS: A total of
      106,391 newborns were screened using the TREC assay over a period of 19 months.
      Five newborns were immediately referred for confirmatory tests, including two
      SCID patients and two patients with persistent T-cell lymphopenia; a third SCID
      patient was found 2 months after the study period. All three SCID cases received
      stem cell transplantation at the age of 2-5 months. We also identified five cases
      of 22q11.2 microdeletion syndrome. During this period, two SCID patients from
      among the unscreened newborns were reported, and they died at ages 3 months and 4
      months, respectively. CONCLUSION: Newborn screening to measure the number of TREC
      copies successfully identifies newborns with T-cell lymphopenia, 22q11.2
      microdeletion syndrome, and other high-risk conditions. Taken together, the
      incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in
      11,821, and further attention to their immune functions is warranted.

PMID- 25618584
TI  - Effects of chlorhexidine on stem cells from exfoliated deciduous teeth.
AB  - BACKGROUND/PURPOSE: Chlorhexidine (CHX) is a type of chemical antiseptic that is
      widely used in dental practice. Stem cells from human exfoliated deciduous teeth
      (SHED) are multipotent cells. However, there is little knowledge about the
      effects of chlorhexidine on SHED cells. The purpose of this study is to
      investigate the effects of CHX on SHED. METHODS: SHED cells were treated with
      0.1%, 0.01%, 0.001%, and 0.0001% CHX for 10 seconds to test the effects of
      different concentrations of CHX on SHED cells. The cells were also treated with
      0.01% CHX for 10 seconds, 1 minute, and 5 minutes to test the time effects of CHX
      on SHED cells. Cell proliferation was investigated by a 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and an autonomously replicating
      sequence (ARS) assay was used for the evaluation of the mineralization potential.
      RESULTS: This study demonstrated that different concentrations of CHX had
      cytotoxic effects on SHED cells in a dose- and time-dependent manner. The
      proliferation of SHED cells was inhibited by approximately 50% by the use of
      0.01% CHX. It was also found that the cell proliferation and mineralization
      potential of SHED cells were inhibited to some degree by different concentrations
      of CHX. CONCLUSION: Different concentrations of CHX can inhibit SHED cell
      proliferation in a dose- and time-dependent manner. In addition, the
      mineralization potential of SHED cells is inhibited to some degree by different
      concentrations of CHX.

PMID- 25618581
TI  - Teaching the basics of autophagy and mitophagy to redox biologists--mechanisms
      and experimental approaches.
AB  - Autophagy is a lysosomal mediated degradation activity providing an essential
      mechanism for recycling cellular constituents, and clearance of excess or damaged
      lipids, proteins and organelles. Autophagy involves more than 30 proteins and is
      regulated by nutrient availability, and various stress sensing signaling
      pathways. This article provides an overview of the mechanisms and regulation of
      autophagy, its role in health and diseases, and methods for its measurement.
      Hopefully this teaching review together with the graphic illustrations will be
      helpful for instructors teaching graduate students who are interested in grasping
      the concepts and major research areas and introducing recent developments in the
      field. 

PMID- 25618585
TI  - The modulation of hypoxia-inducible factor-1alpha/plasminogen activator inhibitor
      1 axis in human gingival fibroblasts stimulated with cyclosporine A.
AB  - BACKGROUND/PURPOSE: The prominent side effect of the immunosuppressive drug
      cyclosporine A (CsA) is gingival overgrowth. Hypoxia-inducible factor (HIF)
      1alpha regulates a wide variety of profibrogenic genes, which are closely
      associated with tissue fibrosis. The aim of this study was to compare HIF-1alpha
      expression in normal gingival tissues and CsA-induced gingival overgrowth
      specimens and further explore the potential mechanisms that may lead to induction
      of HIF-1alpha expression. METHODS: Fifteen CsA-induced gingival overgrowth
      specimens and five normal gingival tissues were examined by immunohistochemistry.
      Western blot was used to investigate the effects of CsA on the expression of HIF
      1alpha in cultured human gingival fibroblasts. The effects of CsA on plasminogen
      activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia.
      RESULTS: HIF-1alpha staining in gingival tissue was stronger in CsA-induced
      gingival overgrowth group than normal gingival group (p < 0.05). The expression
      of HIF-1alpha was significantly higher in CsA-induced gingival overgrowth
      specimens with higher levels of inflammatory infiltrates (p = 0.041). CsA was
      found to upregulate HIF-1alpha protein in a dose-dependent manner (p < 0.05).
      Hypoxia increased CsA-induced PAI-1 protein expression than normoxic conditions
      (p < 0.05). CONCLUSION: These results suggest that HIF-1alpha expression is
      significantly upregulated in CsA-induced gingival overgrowth specimens. The
      activation of HIF-1alpha may promote fibrogenesis by an increase of PAI-1
      expression and a subsequent elevation of extracellular matrix production in
      gingival tissues.

PMID- 25618586
TI  - Managing emergency department overcrowding via ambulance diversion: a discrete
      event simulation model.
AB  - BACKGROUND/PURPOSE: Ambulance diversion (AD) is considered one of the possible
      solutions to relieve emergency department (ED) overcrowding. Study of the
      effectiveness of various AD strategies is prerequisite for policy-making. Our aim
      is to develop a tool that quantitatively evaluates the effectiveness of various
      AD strategies. METHODS: A simulation model and a computer simulation program were
      developed. Three sets of simulations were executed to evaluate AD initiating
      criteria, patient-blocking rules, and AD intervals, respectively. The crowdedness
      index, the patient waiting time for service, and the percentage of adverse
      patients were assessed to determine the effect of various AD policies. RESULTS:
      Simulation results suggest that, in a certain setting, the best timing for
      implementing AD is when the crowdedness index reaches the critical value, 1.0 -
      an indicator that ED is operating at its maximal capacity. The strategy to divert
      all patients transported by ambulance is more effective than to divert either
      high-acuity patients only or low-acuity patients only. Given a total allowable AD
      duration, implementing AD multiple times with short intervals generally has
      better effect than having a single AD with maximal allowable duration.
      CONCLUSION: An input-throughput-output simulation model is proposed for
      simulating ED operation. Effectiveness of several AD strategies on relieving ED
      overcrowding was assessed via computer simulations based on this model. By
      appropriate parameter settings, the model can represent medical resource
      providers of different scales. It is also feasible to expand the simulations to
      evaluate the effect of AD strategies on a community basis. The results may offer
      insights for making effective AD policies.

PMID- 25618582
TI  - Interdependence of tetrapyrrole metabolism, the generation of oxidative stress
      and the mitigative oxidative stress response.
AB  - Tetrapyrroles are involved in light harvesting and light perception, electron
      transfer reactions, and as co-factors for key enzymes and sensory proteins. Under
      conditions in which cells exhibit stress-induced imbalances of photosynthetic
      reactions, or light absorption exceeds the ability of the cell to use
      photoexcitation energy in synthesis reactions, redox imbalance can occur in
      photosynthetic cells. Such conditions can lead to the generation of reactive
      oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS
      accumulation can result in cellular damage and detrimental effects on organismal
      fitness, or ROS molecules can serve as signals to induce a protective or damage
      mitigating oxidative stress signaling response in cells. Induced oxidative stress
      responses include tetrapyrrole-dependent and -independent mechanisms for
      mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be
      contributors to oxidative stress, but are also essential in the oxidative stress
      response to protect cells by contributing to detoxification of ROS. In this
      review, we highlight the interconnection and interdependence of tetrapyrrole
      metabolism with the occurrence of oxidative stress and protective oxidative
      stress signaling responses in photosynthetic organisms. 

PMID- 25618587
TI  - An isodicentric X chromosome with gonadal dysgenesis in a lady without prominent
      somatic features of Turner's syndrome. A case report.
AB  - Isodicentric X chromosomes in general have phenotypes characteristic of the
      resultant X deletions. Gonadotropin levels in Turner's syndrome (TS) girls are
      high, but have a normal biphasic pattern. Here, we report a 21-year-old lady with
      primary amenorrhea. Clinical examination revealed a short neck but no other
      typical stigmata of Turner's syndrome. The levels of gonadotropin were not raised
      to post-menopausal levels. A chromosome study showed a 45,X/46,X,idic(X)(q22)
      karyotype. She was diagnosed as having Turner's syndrome. 

PMID- 25618588
TI  - Prenatal detection and characterization of a psu idic(8)(p23.3) which likely
      derived from nonallelic homologous recombination between two MYOM2-repeats.
AB  - Mosaicism with an isodicentric 8 with a breakpoint at p23.3 [idic(8)(p23.3)] is
      very rare. We report the first prenatal case on a male fetus, in which obstetric
      ultrasound revealed multiple congenital anomalies at 28 weeks of gestation.
      Cytogenetic analysis of amniocytes showed mos 45,XY,-8,psu
      idic(8)(p23.3)[16]/46,XY,psu idic(8)(p23.3)[4], and that of cord blood
      lymphocytes revealed mos 46,XY, psu idic(8)(p23.3)[37]/45,XY,-8,psu
      idic(8)(p23.3)[13]. Fluorescence in situ hybridization studies revealed that the
      break-reunion occurred at the cytoband 8p23.3 within the physical position 2.08
      Mb from the 8p telomere. Chromosomal microarray analyses further assigned the
      duplication/deletion breakpoint at 2.16 Mb (Agilent 244K) and at 2.19 Mb
      (Affymetrix SNP6.0). Analysis of microsatellite DNA indicated that the psu
      idic(8)(p23.3) was derived from the maternal chromosome 8. Together, these
      findings indicate that the fetus was nullisomic for ~2.2 Mb from 8pter, trisomic
      for the rest of chromosome 8 in mosaic condition, and likely had breaks in MYOM2
      repeats of the maternal chromosome 8.

PMID- 25618589
TI  - Expression profiles of antiviral response genes in chicken bursal cells
      stimulated with Toll-like receptor ligands.
AB  - Cells of the adaptive immune system express Toll-like receptors (TLRs) and are
      able to respond to TLR ligands. With this in mind, the goal of the current study
      was to determine the expression of antiviral response genes in the cells of the
      chicken bursa of Fabricius (BF) to stimulation with TLR ligands. We investigated
      initially the response of bursal B cells to CpG-ODN, lipopolysaccharide (LPS) and
      poly(I:C) treatment. The expression level of type I interferons (IFNs) and
      interferon regulatory factor 7 (IRF7) did not differ between CpG-ODN and LPS
      treated groups compared to the non-stimulated cells. Poly(I:C) was the only TLR
      ligand, which has induced significant expression of antiviral innate immune
      response genes from bursal cells. Further in vitro and in vivo studies need to
      examine the efficacy of these antiviral responses against avian viruses. 

PMID- 25618590
TI  - Increased expression of the regulatory T cell-associated marker CTLA-4 in bovine
      leukemia virus infection.
AB  - Regulatory T cells (Tregs) play a critical role in the maintenance of the host's
      immune system. Tregs, particularly CD4(+)CD25(+)Foxp3(+) T cells, have been
      reported to be involved in the immune evasion mechanism of tumors and several
      pathogens that cause chronic infections. Recent studies showed that a Treg
      associated marker, cytotoxic T-lymphocyte antigen 4 (CTLA-4), is closely
      associated with the progression of several diseases. We recently reported that
      the proportion of Foxp3(+)CD4(+) cells was positively correlated with the number
      of lymphocytes, virus titer, and virus load but inversely correlated with IFN
      gamma expression in cattle infected with bovine leukemia virus (BLV), which
      causes chronic infection and lymphoma in its host. Here the kinetics of CTLA-4(+)
      cells were analyzed in BLV-infected cattle. CTLA-4 mRNA was predominantly
      expressed in CD4(+) T cells in BLV-infected cattle, and the expression was
      positively correlated with Foxp3 mRNA expression. To test for differences in the
      protein expression level of CTLA-4, we measured the proportion of CTLA-4
      expressing cells by flow cytometry. In cattle with persistent lymphocytosis (PL),
      mean fluorescence intensities (MFIs) of CTLA-4 on CD4(+) and CD25(+) T cells were
      significantly increased compared with that in control and aleukemic (AL) cattle.
      The percentage of CTLA-4(+) cells in the CD4(+) T cell subpopulation was
      positively correlated with TGF-beta mRNA expression, suggesting that CD4(+)CTLA
      4(+) T cells have a potentially immunosuppressive function in BLV infection. In
      the limited number of cattle that were tested, the anti-CTLA-4 antibody enhanced
      the expression of CD69, IL-2, and IFN-gamma mRNA in anti-programmed death ligand
      1 (PD-L1) antibody-treated peripheral blood mononuclear cells from BLV-infected
      cattle. Together with previous findings, the present results indicate that Tregs
      may be involved in the inhibition of T cell function during BLV infection. 

PMID- 25618591
TI  - The link between testosterone and amygdala-orbitofrontal cortex connectivity in
      adolescent alcohol use.
AB  - Alcohol consumption is one of the most problematic and widespread forms of risk
      taking in adolescence. It has been hypothesized that sex hormones such as
      testosterone play an important role in risk taking by influencing the development
      of brain networks involved in emotion and motivation, particularly the amygdala
      and its functional connections. Connectivity between the amygdala and the
      orbitofrontal cortex (OFC) may be specifically related to alcohol use, given the
      association of this tract with top-down control over behavioral approach
      tendencies. In line with this, prior studies in adults indicate a link between
      alcohol use and functional connectivity between the amygdala and the
      orbitofrontal cortex (OFC), as well as between testosterone and amygdala-OFC
      connectivity. We consolidated these research lines by investigating the
      association between alcohol use, testosterone and resting state functional brain
      connectivity within one large-scale adolescent sample (n=173, aged 12-25 years).
      Mediation analyses demonstrated an indirect effect of testosterone levels on
      alcohol use through amygdala-OFC intrinsic functional connectivity, but only in
      boys. That is, increased testosterone in boys was associated with reduced
      amygdala-OFC connectivity, which in turn was associated with increased alcohol
      intake. This study is the first to demonstrate the interplay between adolescent
      alcohol use, sex hormones and brain mechanisms, thus taking an important step to
      increase our understanding of the mechanisms behind this form of adolescent risk
      taking. 

PMID- 25618592
TI  - In a rat model of panic, corticotropin responses to dorsal periaqueductal gray
      stimulation depend on physical exertion.
AB  - Panic disorder patients are exquisitely and specifically sensitive to
      hypercapnia. The demonstration that carbon dioxide provokes panic in fear
      unresponsive amygdala-calcified Urbach-Wiethe patients emphasizes that panic is
      not fear nor does it require the activation of the amygdala. This is consonant
      with increasing evidence suggesting that panic is mediated caudally at midbrain's
      dorsal periaqueductal gray matter (DPAG). Another startling feature of the
      apparently spontaneous clinical panic is the counterintuitive lack of increments
      in corticotropin, cortisol and prolactin, generally considered 'stress hormones'.
      Here we show that the stress hormones are not changed during DPAG-evoked panic
      when escape is prevented by stimulating the rat in a small compartment. Neither
      did the corticotropin increase when physical exertion was statistically adjusted
      to the same degree as non-stimulated controls, as measured by lactate plasma
      levels. Conversely, neuroendocrine responses to foot-shocks were independent from
      muscular effort. Data are consonant with DPAG mediation of panic attacks. 

PMID- 25618593
TI  - Hydrocortisone accelerates the decay of iconic memory traces: on the modulation
      of executive and stimulus-driven constituents of sensory information maintenance.
AB  - A substantial amount of research documents the impact of glucocorticoids on
      higher-order cognitive functioning. By contrast, surprisingly little is known
      about the susceptibility of basic sensory processes to glucocorticoid exposure
      given that the glucocorticoid receptor density in the human visual cortex exceeds
      those observed in prefrontal and most hippocampal brain regions. As executive
      tasks also rely on these sensory processes, the present study investigates the
      impact of glucocorticoid exposure on different performance parameters
      characterizing the maintenance and transfer of sensory information from iconic
      memory (IM; the sensory buffer of the visual system) to working memory (WM).
      Using a crossover factorial design, we administered one out of three doses of
      hydrocortisone (0.06, 0.12, or 0.24mg/kg bodyweight) and a placebo to 18 healthy
      young men. Thereafter participants performed a partial report task, which was
      used to assess their individual ability to process sensory information. Blood
      samples were concurrently drawn to determine free and total cortisol
      concentrations. The compiled pharmacokinetic and psychophysical data demonstrates
      that free cortisol specifically accelerated the decay of sensory information
      (r=0.46) without significantly affecting the selective information transfer from
      IM to WM or the capacity limit of WM. Specifically, nonparametric regression
      revealed a sigmoid dose-response relationship between free cortisol levels during
      the testing period and the IM decay rates. Our findings highlight that
      glucocorticoid exposure may not only impact on the recruitment of top-down
      control for an active maintenance of sensory information, but alter their passive
      (stimulus-driven) maintenance thereby changing the availability of information
      prior to subsequent executive processing. 

PMID- 25618594
TI  - Oxytocin enhances the expression of morphine-induced conditioned place preference
      in rats.
AB  - Drug addiction is characterized by drug-seeking and drug-taking and has
      devastating consequences on addicts as well as on society. Environmental contexts
      previously associated with drug use can elicit continued drug use and facilitate
      relapse. Accumulating evidence suggests that the neuropeptide oxytocin might be a
      potential treatment for behavioral disorders, including drug addiction. Here, we
      investigated the effects of central oxytocin administration on the acquisition
      and expression of morphine-induced conditioned place preference (CPP), a model
      for measuring the rewarding effects of drugs of abuse, in male Wistar rats.
      Intracerebroventricular (ICV) administration of oxytocin (0.2MUg) or the specific
      oxytocin receptor antagonist (OTA), desGly-NH2, d(CH2)5[Tyr(Me)(2), Thr(4)] OVT,
      (0.75MUg), on the conditioning days did not affect the acquisition of morphine
      induced CPP. By contrast, ICV oxytocin, but not OTA, administration immediately
      prior to the post-conditioning session enhanced the expression of morphine
      induced CPP, possibly by activation of oxytocin receptors in the nucleus
      accumbens shell (NAcSh). The oxytocin enhancement of morphine-induced CPP was not
      associated with any changes in the locomotor activity of morphine-conditioned
      rats. Together, these data suggest that central administration of exogenous
      oxytocin enhances the expression of morphine-induced CPP, at least in part, via
      activation of oxytocin receptors within the NAcSh. 

PMID- 25618595
TI  - Design and synthesis of new bioisosteres of spirooxindoles (MI-63/219) as anti
      breast cancer agents.
AB  - We report herein the design and synthesis of bioisosteres of spirooxindole (MI
      63/219), a small-molecule inhibitors of the MDM2-p53 interaction as anti-breast
      cancer agents. Compound 5b has been exhibiting significant anti-proliferative
      activity in nude mice bearing MCF-7 xenograft tumor. The compound 5b was found to
      act via modulation of MDM2 and p53 expression in breast cancer cells expressing
      wild type p53. Compound 5b stimulated p53 activation, caused modulation of
      downstream effectors p21, pRb, and cyclin D1 which regulate cell cycle. Thus,
      compound triggered G1-S phase cell cycle arrest, which was evident by flow
      cytometric analysis of treated breast cancer cells. Thus, compound 5b restores
      the p53 function, which triggers molecular events consistent with cell cycle
      arrest at G1/S phase. 

PMID- 25618596
TI  - Docking model of the nicotinic acetylcholine receptor and nitromethylene
      neonicotinoid derivatives with a longer chiral substituent and their biological
      activities.
AB  - In the present study, nitromethylene neonicotinoid derivatives possessing
      substituents that contain a sulfur atom, oxygen atom or aromatic ring at position
      5 on the imidazolidine ring were synthesized to evaluate their affinity for the
      nicotinic acetylcholine receptor (nAChR) and their insecticidal activity against
      adult female houseflies. Comparing the receptor affinity of the alkylated
      derivative with the receptor affinity of compounds possessing either ether or
      thioether groups revealed that conversion of the carbon atom to a sulfur atom did
      not influence the receptor affinity, whereas conversion to an oxygen atom was
      disadvantageous for the receptor affinity. The receptor affinity of compounds
      possessing a benzyl or phenyl group was lower than that of the unsubstituted
      compound. Analysis of the three-dimensional quantitative structure-activity
      relationship using comparative molecular field analysis demonstrated that steric
      hindrance of the receptor should exist around the C3 of an n-butyl group attached
      at position 5 on the imidazolidine ring. A docking study of the nAChR-ligand
      model suggested that the ligand-binding region expands as the length of the
      substituent increases by brushing against the amino acids that form the binding
      region. The insecticidal activity of the compounds was positively correlated with
      the receptor affinity by considering logP and the number of heteroatoms,
      including sulfur and oxygen atoms, in the substituents, suggesting that the
      insecticidal activity is influenced by the receptor affinity, hydrophobicity, and
      metabolic stability of the compounds. 

PMID- 25618597
TI  - Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase
      inhibitors.
AB  - A series of novel beta-diketo derivatives which combined the virtues of
      dihydroxypyrimidine carboxamide derived from the evolution of DKA and
      polyhydroxylated aromatics moieties, were designed and synthesized as potential
      HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand
      transfer process of HIV-1 integrase and anti-HIV-1 activity. The result indicates
      that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1
      integrase, but dihydroxylated aromatic derivatives appear little inhibition to
      HIV-1 integrase. In addition, the preliminary structure-activity relationship
      (SAR) of these new derivatives was rationalized by docking studies. 

PMID- 25618598
TI  - Glucose-regulated protein 78 mediates the therapeutic efficacy of 17-DMAG in
      colon cancer cells.
AB  - Glucose-regulated protein 78 (GRP78) is expressed as part of the molecular
      response to endoplasmic reticulum (ER) stress and mediates protein folding within
      the cell. GRP78 is also an important biomarker of cancer progression and the
      therapeutic response of patients with different cancer types. However, the role
      of GRP78 in the cytotoxic effect of 17-DMAG in colon cancer cells remains
      unclear. GRP78 expression was knocked down by small interfering RNA (siRNA). The
      anticancer effects of 17-DMAG were assessed by an 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell-cycle
      analysis, and an Annexin V-propidium iodide (PI) apoptotic assay. We found that
      HT-29 cells expressed a lower level of GRP78 compared with DLD-1 cells. The MTT
      assay revealed that HT-29 cells were more sensitive to 17-DMAG treatment than DLD
      1 cells. GRP78 knock down (GRP78KD) cells demonstrated an increased sensitivity
      to 17-DMAG treatment compared with the scrambled control cells. Based on the cell
      cycle analysis and Annexin V-PI apoptotic assay, apoptosis dramatically increased
      in GRP78KD cells compared with scrambled control DLD-1 cells after these cells
      were treated with 17-DMAG. Finally, we observed a decrease in the level of Bcl-2
      and an increase in the levels of Bad and Bax in GRP78KD cells treated with 17
      DMAG. These results are consistent with an increased sensitivity to 17-DMAG after
      knock down of GRP78. The level of GRP78 expression may determine the therapeutic
      efficacy of 17-DMAG against colon cancer cells.

PMID- 25618599
TI  - Circulating miR-375 and miR-199a-3p as potential biomarkers for the diagnosis of
      hepatocellular carcinoma.
AB  - Aiming to find novel non-invasive biomarkers with high accuracy for the detention
      of early-stage hepatocellular carcinoma (HCC), we examined the predictive power
      of two microRNAs (miR; miR-375 and miR-199a-3p) as potential biomarkers in early
      stage HCC. A total of 234 serum samples (78 samples from HCC patients, 156
      samples from healthy controls) were collected. We measured the levels of the two
      mature microRNAs (miRNAs) (miR-375 and miR-199a-3p) with probe-based stem-loop
      quantitative reverse-transcriptase PCR (RT-qPCR) in all subjects. In addition,
      the correlation between the expression levels of two miRs and clinicopathological
      factors was explored. Receiver operating characteristic curve (ROC) analyses
      revealed that the two serum miRs could be promising biomarkers for HCC, with
      relatively high area under the curve (AUC) values as follows: miR-375, 0. 637
      with 95 % confidence interval (CI) of 0.560-0.741; miR-199a-3p, 0. 883 with 95 %
      CI of 0.827-0.938. Stratified analyses indicated that circulating miR-199a-3p
      showed better predictive value in patients with long-term drinking. Our data
      suggested that circulating miR-375 and miR-199a-3p could be a novel serum
      biomarker for HCC. Nevertheless, further validating and improving study with
      larger sample should be conducted to confirm our results.

PMID- 25618600
TI  - RANK pathway in giant cell tumor of bone: pathogenesis and therapeutic aspects.
AB  - Giant cell tumor is a relatively uncommon but painful tumor of bone, which can
      metastasize to the lungs. The RANK pathway is often reported to be involved in
      the pathogenesis of giant cell tumor of bone (GCTB). This pathway is a key
      signaling pathway of bone remodeling that plays a critical role in
      differentiation of precursors into multinucleated osteoclasts, and activation of
      osteoclasts leading to bone resorption. Dysregulation of RANK ligand (RANKL)-RANK
      osteoprotegerin (OPG) signaling cascade induces the imbalance between bone
      formation and bone resorption, which leads to the changes in bone mass, increases
      osteoclast-mediated bone destruction, bone metastasis, and the progression of
      existing skeletal tumors. Recent evidences have shown that targeting the
      components of RANKL-RANK-OPG signaling pathway is a promising approach in the
      treatment of GCTB. This review study has focused on the association of RANKL-RANK
      OPG pathway in the pathogenesis and progression of GCTB as well as discussed the
      possible therapeutic strategies by targeting this pathway. 

PMID- 25618602
TI  - MU-Opioid receptor gene (OPRM1) polymorphism in patients with breast cancer.
AB  - Structure-dependent MU-opioid receptor (MOR) activity is an important element in
      cancer opioid analgesic effectiveness. It is widely accepted that guanine (G)
      substitution for adenine (A) at OPRM1 gene sequence position 118 changes receptor
      glycosylation pattern. This is associated with decreased binding ability in both
      exogenous and endogenous opioids, resulting in increased human pain resistance.
      The endogenous opioid system's function in body homeostasis maintenance is
      considered mainly regulatory, so its participation in breast tumor formation and
      progression is identified herein. We examine the association of the most frequent
      MOR (A118G) gene polymorphism on breast cancer risk in a Northeastern Polish
      population by PCR-RFLP comparison of A and G allele frequency at OPRM1 gene A118G
      polymorphic site in breast cancer-diagnosed patients with healthy control group
      frequencies. Our results highlight a strong association between G allele presence
      at MU-opioid receptor A118G and increased breast cancer incidence (OR = 3.3, 95 %
      CI 2.2-5.0, p < 0.0001) and female gender (OR = 2.0, 95 % CI 1.4-2.9, p =
      0.0004). Consequently, OPRM1 G allele presence at that site is a highly
      significant risk factor in breast cancer development.

PMID- 25618601
TI  - Post-transcriptional regulation of long noncoding RNAs in cancer.
AB  - It is a great surprise that the genomes of mammals and other eukaryotes harbor
      many thousands of long noncoding RNAs (lncRNAs). Although these long noncoding
      transcripts were once considered to be simply transcriptional noise or cloning
      artifacts, multiple studies have suggested that lncRNAs are emerging as new
      players in diverse human diseases, especially in cancer, and that the molecular
      mechanisms of lncRNAs need to be elucidated. More recently, evidence has begun to
      accumulate describing the complex post-transcriptional regulation in which
      lncRNAs are involved. It was reported that lncRNAs can be implicated in
      degradation, translation, pre-messenger RNA (mRNA) splicing, and protein
      activities and even as microRNAs (miRNAs) sponges in both a sequence-dependent
      and sequence-independent manner. In this review, we present an updated vision of
      lncRNAs and summarize the mechanism of post-transcriptional regulation by
      lncRNAs, providing new insight into the functional cellular roles that they may
      play in human diseases, with a particular focus on cancers. 

PMID- 25618604
TI  - Gaps in knowledge: tracking and explaining gender differences in health
      information seeking.
AB  - Self-directed health information seeking has become increasingly common in recent
      years, yet there is a substantial body of evidence suggesting that females are
      more likely to engage in information seeking than males. Previous research has
      largely ignored the significance of this difference as both an empirical and a
      theoretical finding. The current study has two goals, seeking to track this sex
      gap over time and to test explanations for its existence. The three explanations
      tested are based in past findings of gendered division of childcare labor,
      gendered reactivity to illness, and gendered perceived risk of illness. These
      were tested using multiple dependent variables from both repeated cross sectional
      data and 2012 data from the Health Information Trends Survey (HINTS). Results
      show that females are significantly more likely to look for cancer information,
      information in general, and information over the Internet over time than males,
      though the gap may be closing in the case of cancer information. The three
      explanations also received little clear support though perceived risk of getting
      cancer acted as a mediator through which men may be less likely to look for
      cancer information. Based on this analysis it is clear that a sex gap in
      information seeking is present and theories of masculinity and health may hold
      promise in some contexts but additional explanations are needed. 

PMID- 25618603
TI  - Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced
      BNIP3 expression.
AB  - Baicalein, a flavonoid compound, is one of the active constituents of the root of
      Scutellariae Radix. Its antitumor effects have attracted widespread attention
      worldwide. One of its major functions is to induce the apoptosis of tumor cells,
      but the antitumor mechanism is currently unclear. In the present study, we found
      that baicalein increased MG-63 cell mortality in a dose-dependent manner.
      Meanwhile, baicalein activated apoptosis through induced intracellular reactive
      oxygen species (ROS) generation, and that ROS scavenger N-acetyl-cysteine (NAC),
      glutathione (GSH), and superoxide dismutase (SOD) apparently inhibited
      intracellular ROS production, consequently attenuating the baicalein-induced
      apoptosis. Baicalein also induce the mitochondrial fragmentation which precedes
      the cell apoptosis. This morphological alteration is accompanied by an increase
      in the expression of the protein BNIP3 as well as Mul1 and Drp1. Furthermore, we
      show that the inhibition of BNIP3 expression can inhibit cell apoptosis by
      baicalein treatment. Taken together, our results bring the evidence of a
      mechanism that links apoptosis and ROS-induced BNIP3 expression in MG-63 cells
      with bacalein treatment and suggest that baicalein has a good potential as an
      anti-osteosarcoma drug.

PMID- 25618605
TI  - Resilience in the face of post-election violence in Kenya: the mediating role of
      social networks on wellbeing among older people in the Korogocho informal
      settlement, Nairobi.
AB  - Older people in slum settings are a vulnerable sub-group during crises, yet have
      received minimal attention in the development discourse. This paper examines the
      protective role of different types of social networks for older slum dwellers'
      wellbeing during adversity by investigating the relationship between social
      networks, the Kenyan 2007/08 post-election violence, and dimensions of wellbeing
      namely self-rated health, life satisfaction and happiness amongst older people in
      the Korogocho slum, Nairobi. The analyses are based on conditional change
      logistic regression models using data from a unique longitudinal survey of the
      health and wellbeing of older people. The results show that maintaining or
      increasing formal local networks reduced the detrimental effects of the post
      election violence for older people's wellbeing, whilst household environment and
      informal local and non-local networks did not influence the relationship.
      Consequently, the paper provides evidence that supporting inclusive community
      organisations which are accessible to older people can be valuable in promoting
      the resilience of this population group. 

PMID- 25618606
TI  - The moderating effect of self-efficacy on normal-weight, overweight, and obese
      children's math achievement: a longitudinal analysis.
AB  - Increased body weight is associated with decreased cognitive function in school
      aged children. The role of self-efficacy in shaping the connection between
      children's educational achievement and obesity-related comorbidities has not been
      examined to date. Evidence of the predictive ability of self-efficacy in children
      is demonstrated in cognitive tasks, including math achievement scores. This study
      examined the relationship between self-efficacy and math achievement in normal
      weight, overweight, and obese children. I hypothesized that overweight and obese
      children with higher self-efficacy will be less affected in math achievement than
      otherwise comparable children with lower self-efficacy. I tested this prediction
      with multilevel growth modeling techniques using the ECLS-K 1998-1999 survey
      data, a nationally representative sample of children. Increased self-efficacy
      moderates the link between body weight and children's math achievement by
      buffering the risks that increased weight status poses to children's cognitive
      function. My findings indicate that self-efficacy moderates math outcomes in
      overweight, but not obese, children. 

PMID- 25618607
TI  - Social determinants and psychological distress among Aboriginal and Torres Strait
      islander adults in the Australian state of Victoria: a cross-sectional population
      based study.
AB  - Aboriginal and Torres Strait Islander adults in the Australian state of Victoria
      have a higher prevalence of psychological distress than their non-Aboriginal and
      Torres Strait Islander counterparts. We sought to explain this inequality,
      focussing on the social determinants of health. We used population-based survey
      data from the 2008 Victorian Population Health Survey; a cross-sectional landline
      computer-assisted telephone survey of 34,168 randomly selected adults. We defined
      psychological distress as a score of 22 or more on the Kessler 10 Psychological
      Distress scale. We used logistic regression to identify socio-demographic
      characteristics and social capital indicators that were associated with
      psychological distress. We then created multivariable models to explore the
      association between psychological distress and Aboriginal and Torres Strait
      Islander status that incorporated all significant socioeconomic status (SES) and
      social capital variables, adjusting for all non-SES socio-demographic
      characteristics. Aboriginal and Torres Strait Islander Victorians (24.5%) were
      more than twice as likely than their non-Aboriginal and Torres Strait Islander
      counterparts (11.3%) to have psychological distress (odds ratio (OR) = 2.56, 95%
      confidence interval; 1.67-3.93). Controlling for SES, negative perceptions of the
      residential neighbourhood, lack of social support from family, social and civic
      distrust, and all non-SES socio-demographic variables (age, sex, marital status,
      household composition, and rurality), rendered the previously statistically
      significant inequality in the prevalence of psychological distress, between
      Aboriginal and Torres Strait Islander Victorians and their non-Aboriginal and
      Torres Strait Islander counterparts, insignificant at the p = 0.05 level (OR =
      1.50; 0.97-2.32). Psychological distress is an important health risk factor for
      Aboriginal and Torres Strait Islander adults that has yet to be widely
      acknowledged and addressed. Addressing the underlying inequalities in SES and
      social capital may be the key to addressing the inequality in psychological
      distress.

PMID- 25618608
TI  - Determinants and disparities: a simulation approach to the case of child health
      care.
AB  - Though there is much agreement on the importance of the social determinants of
      health, debate continues on suitable empirically-based models to underpin efforts
      to tackle health and health care disparities. We demonstrate an approach that
      uses a dynamic micro-simulation model of the early life course, based on
      longitudinal data from a New Zealand cohort of children born in 1977, and
      counterfactual reasoning applied to a range of outcomes. The focus is on health
      service use with a comparison to outcomes in non-health domains, namely
      educational attainment and antisocial behaviour. We show an application of the
      model to test scenarios based on modifying key determinants and assessing the
      impact on putative outcomes. We found that appreciable improvement was only
      effected by modifying multiple determinants; structural determinants were
      relatively more important than intermediary ones as potential policy levers;
      there was a social gradient of effect; and interventions bestowed the greatest
      benefit to the most disadvantaged groups with a corresponding reduction in
      disparities between the worst-off and the best-off. Our findings provide evidence
      on how public policy initiatives might be more effective acting broadly across
      sectors and across social groups, and thus make a real difference to the most
      disadvantaged. 

PMID- 25618609
TI  - The evaluation of the compatibility of electronic patient record (EPR) system
      with nurses' management needs in a developing country.
AB  - INTRODUCTION: In a developing country like Iran, wasting economic resources has a
      number of negative consequences. Therefore, it is crucial that problems of
      introducing new electronic systems be identified and addressed early to avoid
      failure of the programs. The purpose of this study was to evaluate head nurses'
      and supervisors' perceptions about the efficiency of the electronic patient
      record (EPR) system and its impact on nursing management tasks in order to
      provide useful recommendations. METHODS: This descriptive study was performed in
      teaching hospitals affiliated to Semnan University of Medical Sciences, Iran. An
      anonymous self-administered questionnaire was developed. Head nurses and
      supervisors were included in this study. RESULTS: It was found that the EPR
      system was immature and was not proportionate to the operational level. Moreover,
      few head nurses and supervisors agreed on the benefits of the EPR system on the
      performance of their duties such as planning, organizing, budgeting, and
      coordinating. CONCLUSION: It is concluded that in addition to the technical
      improvements, the social and cultural factors should be considered to improve the
      acceptability of electronic systems through social marketing in the different
      aspects of nursing management. It is essential that health information technology
      managers emphasize on training head nurses and supervisors to design technology
      corresponding to their needs rather than to accept poorly designed technology.

PMID- 25618610
TI  - Clinical supervisors' perspectives on delivering work integrated learning: a
      survey study.
AB  - BACKGROUND: Previous research has indicated a disconnect between academic nursing
      programmes and workplace learning environments. Nurse supervisors and clinical
      practitioners have reported inadequate information and training on how to support
      students of nursing to learn in the clinical setting. OBJECTIVE: This study aimed
      to investigate the level of confidence that clinical supervisors have in relation
      to specific components of supporting student learning in the work place. DESIGN:
      Survey of clinical nurse supervisors. SETTING: Simulation-based clinical
      reasoning workshops. PARTICIPANTS: Sixty participants: fifty nine registered
      nurses, including nurse managers and clinical nurse educators, and one allied
      health professional. METHODS: Survey using Likert scales and free-text questions.
      RESULTS: The findings indicated that clinicians were confident in sharing their
      knowledge and experience with students and making them feel welcome in the work
      place, they were less confident about what were the significant learnings in
      relation to students' academic programme. Registered nurses supervising students
      were experienced clinicians with many role responsibilities, which were perceived
      as barriers to the role of clinical supervisor. Participants reported that they
      would like tools to assist them with developing links to the academic programme.
      They considered that these tools would support student learning and remediation
      in the work place. CONCLUSIONS: This study found that the abilities of
      supervisors to support student learning is an identified gap impacting on work
      integrated learning. The results indicated the need for a professional
      development workshop, to enable clinical supervisors to move beyond promoting a
      supervision model, towards a theoretical framework for assisting and guiding
      students to learn. Addressing this deficit will improve growth and change in
      student learning in the work place.

PMID- 25618612
TI  - PENS position statement on linear growth measurement of children.

PMID- 25618611
TI  - Appropriate use of vancomycin in a pediatric emergency department through the use
      of a standardized electronic guideline.
AB  - OBJECTIVES: (a) Compare utilization of vancomycin in the ED prior to and after
      implementation of standardized treatment guideline and order template (STGOT);
      (b) assess the appropriate use as initial therapy based on indication versus
      admitting diagnosis. METHODS: Chart audits on all patients who received
      vancomycin and were admitted. Overall utilization and appropriateness of starting
      therapy were compared pre-and post-STGOT implementation. RESULTS: Overall
      utilization of vancomycin was 4% pre-STGOT compared to 3% post-STGOT; 98% of
      patients pre-STGOT compared to 99% post-STGOT received vancomycin appropriately.
      CONCLUSION: There was no difference in vancomycin utilization and appropriateness
      of initiating therapy after STGOT implementation.

PMID- 25618613
TI  - On universality of scaling law describing roughness of triple line.
AB  - The fine structure of the three-phase (triple) line was studied for different
      liquids, various topographies of micro-rough substrates and various wetting
      regimes. Wetting of porous and pillar-based micro-scaled polymer surfaces was
      investigated. The triple line was visualized with the environmental scanning
      electron microscope and scanning electron microscope for the "frozen" triple
      lines. The value of the roughness exponent zeta for water (ice)/rough polymer
      systems was located within 0.55-0.63. For epoxy glue/rough polymer systems
      somewhat lower values of the exponent, 0.42 < zeta < 0.54, were established. The
      obtained values of zeta were close for the Cassie and Wenzel wetting regimes,
      different liquids, and different substrates' topographies. Thus, the above values
      of the exponent are to a great extent universal. The switch of the exponent, when
      the roughness size approaches to the correlation length of the defects, is also
      universal.

PMID- 25618614
TI  - Brownian motion of optically anisotropic spherical particles in polymeric
      suspensions.
AB  - We studied the rotational and translational diffusion of optically anisotropic
      liquid crystal particles embedded in semidiluted polymer solutions of Poly
      Ethylene-Oxide (PEO) at different concentrations and different molecular weights.
      The polymer radius of gyration was chosen to be similar to the size of the probe
      particles and the polymer concentrations used are just above the crossover
      concentration. Thus, the system consists of solid probe particles moving in a sea
      of overlapping particles of similar size. We found that the behavior of both
      particle dynamics, rotational and translational, is similar in the range of
      concentrations considered here. In both cases, two linear diffusive regimes are
      observed, separated by a subdiffusive time interval. The spatial scale at which
      this intermediate regime appears shows a dependence on both the polymer
      concentration and molecular weight, and has a value similar to the thickness of
      the polymer-depleted layer usually found in this kind of systems. Additionally,
      we observe that the colloidal dynamic scales with the overlapping degree of the
      polymer particles. 

PMID- 25618615
TI  - Hemoglobin, hematocrit, and changes in cerebral blood flow: the Second
      Manifestations of ARTerial disease-Magnetic Resonance study.
AB  - Hemoglobin and hematocrit are important determinants of blood viscosity and
      arterial oxygen content and may therefore influence cerebral blood flow (CBF). We
      examined cross-sectional and prospective associations of hemoglobin and
      hematocrit with CBF in 569 patients with manifest arterial disease (mean age 57
      +/- 10 years) with available data on magnetic resonance angiography to measure
      parenchymal CBF. Mean (SD) parenchymal CBF at baseline was 52.3 (9.8) mL/min/100
      mL and decreased with 1.5 (11.0) mL/min/100 mL after on average 3.9 years of
      follow-up. Linear regression analyses showed that greater hemoglobin and
      hematocrit values were associated with lower baseline parenchymal CBF and more
      decline in parenchymal CBF over time, independent of cardiovascular risk factors,
      use of antiplatelet drugs, anticoagulants, or diuretics, and brain measures:
      adjusted mean differences (95% confidence interval [CI]) in decline in
      parenchymal CBF between patients in the lower and upper quartiles of hemoglobin
      and hematocrit were -2.48 (95% CI -3.70 to -1.25) and -3.69 (95% CI -5.45 to 
      1.94) mL/min/100 mL. Higher hemoglobin and hematocrit were associated with lower
      baseline parenchymal CBF and a greater decline in parenchymal CBF over time,
      possibly as a result of physiological compensating mechanisms.

PMID- 25618616
TI  - Sleep-dependent motor memory consolidation in older adults depends on task
      demands.
AB  - It is often suggested that sleep-dependent consolidation of motor learning is
      impaired in older adults. The current study challenges this view and suggests
      that the degree of motor consolidation seen with sleep in older age groups
      depends on the kinematic demands of the task. We show that, when tested with a
      classic sequence learning task, requiring individuated finger movements, older
      adults did not show sleep-dependent consolidation. By contrast, when tested with
      an adapted sequence learning task, in which movements were performed with the
      whole hand, sleep-dependent motor improvement was observed in older adults. We
      suggest that age-related decline in fine motor dexterity may in part be
      responsible for the previously described deficit in sleep-dependent motor
      consolidation with aging. 

PMID- 25618619
TI  - A new concept to broaden access to molecular testing.

PMID- 25618618
TI  - Immunotherapy in cancer care: understanding the impact of shifting treatment
      paradigms in the managed care setting.

PMID- 25618617
TI  - Whole genome sequences of 2 octogenarians with sustained cognitive abilities.
AB  - Although numerous genetic variants affecting aging and mortality have been
      identified, for example, apolipoprotein E epsilon4, the genetic component
      influencing cognitive aging has not been fully defined yet. A better knowledge of
      the genetics of aging will prove helpful in understanding the underlying
      biological processes. Here, we describe the whole genome sequences of 2 female
      octogenarians. We provide the repertoire of genomic variants that the 2
      octogenarians have in common. We also describe the overlap with the previously
      reported genomes of 2 supercentenarians-individuals aged >=110 years. We assessed
      the genetic disease propensities of the octogenarians and non-aged control
      genomes and could not find support for the hypothesis that long-lived healthy
      individuals might exhibit greater genetic fitness than the general population.
      Furthermore, there is no evidence for an accumulation of previously described
      variants promoting longevity in the 2 octogenarians. These findings suggest that
      genetic fitness, as currently defined, is not the sole factor enabling an
      increased life span. We identified a number of healthy-cognitive-aging candidate
      genetic loci awaiting confirmation in larger studies.

PMID- 25618620
TI  - USPSTF recommends BRCA testing in women based on familial history.

PMID- 25618621
TI  - Controversial findings on the value of mammography to be 'dissected?? at Miami
      Breast Cancer Conference.

PMID- 25618622
TI  - Dietary patterns, and effect on cancer, get attention from advisory panel.

PMID- 25618623
TI  - FDA grants accelerated approval for ibrutinib for CLL.

PMID- 25618624
TI  - Ramucirumab combination improves OS and PFS in NSCLC.

PMID- 25618625
TI  - Physician practices, healthcare organizations see own staff as source of security
      breaches.

PMID- 25618626
TI  - Nivolumab provides favorable results in patients with advanced melanoma.

PMID- 25618627
TI  - Understanding and addressing barriers to recruitment.

PMID- 25618628
TI  - Proteomic advances hold promise for precision medicine.

PMID- 25618629
TI  - QOPI, the ASCO initiative, improves compliance and promotes quality of patient
      care.

PMID- 25618630
TI  - Targeted programmed cell death in lung cancer treatment.

PMID- 25618631
TI  - 50th anniversary report: even more known about smoking, cancer connections.

PMID- 25618632
TI  - Effects of heavy metals on ultrastructure and Hsp70 induction in Lemna minor L.
      exposed to water along the Sarno River, Italy.
AB  - The effects of freshwater pollution in the highly contaminated river Sarno
      (Campania, Southern Italy) have been evaluated using bags containing the aquatic
      plant Lemna minor (Lemnacee, Arales), in order to determine morpho-physiological
      modifications as a response to pollutants. The exposition of Lemna bags for 7
      days on three different sites along the river path showed alterations in
      chloroplasts and vacuoles shape and organization. Moreover, some specimens were
      exposed in vitro at the same heavy metal (HM) concentrations measured in the
      polluted sites of the river, and compared with data from the bag experiment; to
      verify the dose and time dependent effects, samples were exposed to HM in vitro
      at concentrations ranging from 10(-6) to 10(-4)M up to 7 days. Transmission
      electron microscopy (TEM) observations on in vitro plants confirmed that
      ultrastructural alterations affected most of plastids and the shape of different
      subcellular structures, namely vacuoles; in in vitro stressed specimens, Heat
      Shock Proteins 70 (Hsp70) levels changed, in dependence of changing levels of HM
      measured in different sites along the river path. Thus L. minor exhibited a
      possible correlation between the levels of HM pollution and Hsp70 occurrence;
      interestingly, the data presented showed that copper specifically increased Hsp70
      levels at concentrations detected in polluted river waters, whereas cadmium and
      lead did not; on the other side, the latter represent highly toxic elements when
      specimens were exposed to higher levels in vitro. The effects of specific
      elements in vitro are compared to those observed in bags exposed along the river
      path; thus results are examined in order to propose L. minor as an organism able
      to be utilized to monitor heavy metals pollution; the possibility of using Hsp70s
      as specific markers of HM pollution is discussed. 

PMID- 25618633
TI  - Molecularly imprinted solid phase extraction of fluconazole from pharmaceutical
      formulations.
AB  - This work encompasses a direct and coherent strategy to synthesise a molecularly
      imprinted polymer (MIP) capable of extracting fluconazole from its sample. The
      MIP was successfully prepared from methacrylic acid (functional monomer),
      ethyleneglycoldimethacrylate (crosslinker) and acetonitrile (porogenic solvent)
      in the presence of fluconazole as the template molecule through a non-covalent
      approach. The non-imprinted polymer (NIP) was prepared following the same
      synthetic scheme, but in the absence of the template. The data obtained from
      scanning electronic microscopy, infrared spectroscopy, thermogravimetric and
      nitrogen Brunauer-Emmett-Teller plot helped to elucidate the structural as well
      as the morphological characteristics of the MIP and NIP. The application of MIP
      as a sorbent was demonstrated by packing it in solid phase extraction cartridges
      to extract fluconazole from commercial capsule samples through an offline
      analytical procedure. The quantification of fluconazole was accomplished through
      UPLC-MS, which resulted in LOD<=1.63*10(-10) mM. Furthermore, a high percentage
      recovery of 91+/-10% (n=9) was obtained. The ability of the MIP for selective
      recognition of fluconazole was evaluated by comparison with the structural
      analogues, miconazole, tioconazole and secnidazole, resulting in percentage
      recoveries of 51, 35 and 32%, respectively.

PMID- 25618634
TI  - Determination of imidacloprid in water samples via photochemically induced
      fluorescence and second-order multivariate calibration.
AB  - This paper presents a new method for the determination of imidacloprid in water
      samples; one of the most widely used neonicotinoid pesticides in the farming
      industry. The method is based on the measurement of excitation-emission spectra
      of photo-induced fluorescence (PIF-EEMs) associated with second-order
      multivariate calibration with a parallel factor analysis (PARAFAC) and unfolded
      partial least squares coupled to residual bilinearization (U-PLS/RBL). The second
      order advantage permitted the determination of imidacloprid in the presence of
      potential interferences, which also shows photo-induced fluorescence (other
      pesticides and/or unexpected compounds of the real samples). The photoreaction
      was performed in 100-MUl disposable micropipettes. As a preliminary step, solid
      phase extraction on C18 (SPE-C18) was applied to concentrate the analyte and
      diminish the limit of detection. The LOD was approximately 1 ng mL(-1), which is
      suitable for detecting imidacloprid in water according to the guidelines
      established in North America and Europe. The PIF-EEMs coupled to PARAFAC or U
      PLS/RBL was successfully applied for the determination of imidacloprid in
      different real water samples, with an average recovery of 101+/-10%.

PMID- 25618635
TI  - Synthesis of polyethyleneimine capped carbon dots for preconcentration and slurry
      sampling analysis of trace chromium in environmental water samples.
AB  - Carbon dots capped with polyethyleneimine (CD-PEI) were synthesized and applied
      in selective separation and preconcentration of trace Cr(VI). Dispersed particle
      extraction (DPE) slurry sampling with flame atomic absorption spectrometry (FAAS)
      was used to selectively and sensitively determine Cr(VI) in water samples. The as
      synthesized CD-PEI was confirmed by Fourier transform infrared spectroscopy, high
      resolution transmission electron microscopy, elemental analysis, fluorescence and
      zeta potential measurement. The adsorption of Cr(VI) on CD-PEI was evaluated. Its
      isothermal adsorption was studied and fitted in the Langmuir model. Nearly 85% of
      Cr(VI) was adsorbed within 10 min showed that the CD-PEI exhibited fairly fast
      kinetics for the sorption of Cr(VI). Experimental conditions, including the
      content and size of CD-PEI, sample pH, adsorption time, sample volume, slurry
      volume and interfering ions, were further optimized to obtain efficient
      preconcentration and high-precision determination of Cr(VI). CD-PEI with small
      size turned to be a good candidate for the preparation of slurry. CD-PEI served
      not only as a promising adsorbent for separation and preconcentration of Cr, but
      also a signal-enhancing agent in FAAS. The method achieved an enhancement factor
      of 30 and a detection limit (S/N=3) of 0.21 ug L(-1) Cr(VI) with a consumption of
      14.0 mL sample and an adsorption time of 5 min, which provided two times of
      signal enhancement. The RSD for 11 replicate measurements of 5.0 ug L(-1) Cr(VI)
      was 2.8%. The possible signal enhancement mechanism was proposed. The developed
      method has been applied to determine trace Cr(VI) in a variety of water samples.

PMID- 25618636
TI  - Determination of fungicide carbendazim in water and soil samples using dispersive
      liquid-liquid microextraction and microvolume UV-vis spectrophotometry.
AB  - This article presents a new and sensitive method for the determination of trace
      amounts of fungicide carbendazim by dispersive liquid-liquid microextraction
      (DLLME) combined with UV-vis spectrophotometry. The method is based on the
      reduction of Fe(III) to Fe(II) by carbendazim, its reaction with potassium
      ferricynide to form a blue product and extraction into CCL4 by DLLME technique
      using methyltrioctylammonium chloride (Aliquat 336) as a disperser agent. Under
      the established optimum conditions, the calibration graph was linear in the range
      of 5-600 ng mL(-1) of carbendazim with a limit of detection of 2.1 ng mL(-1). The
      relative standard deviations for eight replicate determinations of 50 and 300 ng
      mL(-1) of carbendazim were 3.9% and 1.0%, respectively. The proposed method was
      successfully applied to determination of carbendazim in soil and water samples.

PMID- 25618637
TI  - Diagnostic applications of gastric carcinoma cell aptamers in vitro and in vivo.
AB  - Gastric carcinoma is the most malignant tumor. Due to lacking of efficient means
      to diagnose the cancer at the early stage, it is necessary to develop effective
      molecular probes for early diagnosis and treatment. We have selected aptamers
      with high specificity and affinity against SGC7901 cells by cell-SELEX
      (Systematic Evolution of Ligands by Exponential Enrichment) method, which shown
      important clinical applications: (1) Specific recognize human gastric tumor
      tissues compared to the normal tissues. (2)When used to capture cancerous cells,
      the aptamer-functionalized fluorescent-magnetic nanospheres (FMNS) could
      specifically capture 93% target cancer cells and about 70% target cells can be
      released. (3) The aptamer probe displayed a quenched fluorescence in the absence
      of target cancer cells and went through a conformational transformation upon
      binding to target cancer cells that induced fluorescence. (4) The aptamer probe
      could target gastric tumors transplanted into mice with obvious fluorescence. The
      newly generated aptamers hold great potential in early cancer diagnosis.

PMID- 25618638
TI  - Fluorometric flow-immunoassay for alkylphenol polyethoxylates on a microchip
      containing a fluorescence detector comprised of an organic light emitting diode
      and an organic photodiode.
AB  - A compact fluorescence detector was constructed on a microchip from an organic
      light emitting diode (OLED) as the light source and an organic photodiode (OPD)
      as the photo-detector and was used in an immunoassay for alkylphenol
      polyethoxylates (APE). The OLED based on a terbium complex emitted a sharp light
      at the main wavelength of 546 nm with a full width at half maximum of 9 nm. The
      incident photo-to-current conversion efficiency (IPCE) of the OPD fabricated with
      Fullerene 70 (C70) and tris[4-(5-phenylthiopen-2-yl)phenyl]-amine (TPTPA) was
      approximately 44% for light at a wavelength of 586 nm. The performance of the
      fluorescence detector was evaluated for the determination of resorufin
      (lambda(em)=586 nm) and the photocurrent of the OPD due to the fluorescence of
      resorufin was proportional to the concentration of resorufin in the range from 0
      to 18 uM with a detection limit (S/N=3) of 0.6 uM. The fluorescence detector was
      successfully utilized in a competitive enzyme-linked immunosorbent assay for APE,
      where an anti-APE antibody was immobilized on the surface of the channel of the
      Polydimethylsiloxane (PDMS) microchip or on the surface of magnetic microbeads.
      After an immunoreaction with a sample solution of APE containing a horse radish
      peroxidase (HRP)-labeled APE, the fluorescence of resorufin generated just after
      introduction of a mixed solution of Amplex Red and H2O2 was measured using the
      fluorescence detector. The calibration curve for the photocurrent signals of the
      OPD due to the fluorescence of resorufin against the logarithmic concentration of
      APE was sigmoidal in shape. The detection limits defined as IC80 were ca. 1 ppb
      and ca. 2 ppb, respectively, for the methods using the anti-APE antibody
      immobilized on the surface of the microchannel and in the case where the antibody
      was immobilized on the surface of magnetic microbeads.

PMID- 25618639
TI  - Detection of biomarkers for inflammatory diseases by an electrochemical
      immunoassay: the case of neopterin.
AB  - An electrochemical immunoassay for neopterin was developed using recently
      produced specific antibodies immobilized to protein A-coated magnetic beads in
      combination with differential pulse voltammetry and screen-printed array of
      electrodes. Neopterin-alkaline phosphatase conjugate was used as label in a
      competitive assay format. Multiplexed analysis of neopterin was demonstrated by
      replacing the traditional ELISA with electrochemical detection and the
      traditional plastic wells with screen-printed array of electrodes. The optimized
      electrochemical method, based on polyclonal antibodies, reached a limit of
      detection of 0.008 ng/mL with an average RSD %=10. Serum samples collected from
      patients with sepsis, healthy volunteers and other patients without a confirmed
      clinical diagnosis were also analyzed. The obtained results, compared with those
      of a commercial ELISA kit, had a significant correlation, showing the possibility
      to distinguish among the serum samples from ill or healthy subjects.

PMID- 25618640
TI  - One-pot synthesis of gold nanoclusters with bright red fluorescence and good
      biorecognition abilities for visualization fluorescence enhancement detection of
      E. coli.
AB  - A facile one-pot strategy was developed for the synthesis of lysozyme
      functionalized fluorescence gold nanoclusters (AuNCs). The lysozymes added to
      reduce Au(3+) ions and stabilize the AuNCs during the synthesis were coated on
      the AuNCs surface and retained their specific recognition ability for bacteria
      such as Escherichia coli (E. coli). Based on such ability, these AuNCs were
      specifically attached onto the surface of E. coli, which resulted in great red
      fluorescence enhancement. Nevertheless, the bovine serum albumin (BSA) stabilized
      AuNCs could not recognize E. coli and no fluorescence enhancement was observed.
      Upon the addition of E. coli, the red fluorescence intensity of lysozyme-AuNCs
      was enhanced linearly over the range of 2.4*10(4) -6.0*10(6) CFU/mL of E. coli
      with high sensitivity (LOD=2.0*10(4) CFU/mL, S/N=3). The visualization
      fluorescence evolution may enable the rapid and real-time detection of bacteria.
      This study may be extended to other functional proteins such as antibody, enzyme,
      and peptide functionalized nanoclusters while retaining the bioactivity of
      coating proteins and find wide applications in the fields of biochemistry and
      biomedicine.

PMID- 25618641
TI  - Electrochemical determination of the anticancer drug taxol at a ds-DNA modified
      pencil-graphite electrode and its application as a label-free electrochemical
      biosensor.
AB  - In this study a novel biosensor for determination of taxol is described. The
      interaction of taxol with salmon-sperm double-stranded DNA (ds-DNA) based on the
      decreasing of the oxidation signals of guanine and adenine bases was studied
      electrochemically with a pencil-graphite electrode (PGE) using a differential
      pulse voltammetry (DPV) method. The decreases in the intensity of the guanine and
      adenine oxidation signals after interaction with taxol were used as indicator
      signals for the sensitive determination of taxol. DPV exhibits a linear dynamic
      range of 2.0*10(-7)-1.0*10(-5) M for taxol with a detection limit of 8.0*10(-8)
      M. Finally, this modified electrode was used for determination of taxol in some
      real samples.

PMID- 25618642
TI  - Analysis of the polymeric fractions of scrap from mobile phones using laser
      induced breakdown spectroscopy: chemometric applications for better data
      interpretation.
AB  - Because of their short life span and high production and consumption rates,
      mobile phones are one of the contributors to WEEE (waste electrical and
      electronic equipment) growth in many countries. If incorrectly managed, the
      hazardous materials used in the assembly of these devices can pollute the
      environment and pose dangers for workers involved in the recycling of these
      materials. In this study, 144 polymer fragments originating from 50 broken or
      obsolete mobile phones were analyzed via laser-induced breakdown spectroscopy
      (LIBS) without previous treatment. The coated polymers were mainly characterized
      by the presence of Ag, whereas the uncoated polymers were related to the presence
      of Al, K, Na, Si and Ti. Classification models were proposed using black and
      white polymers separately in order to identify the manufacturer and origin using
      KNN (K-nearest neighbor), SIMCA (Soft Independent Modeling of Class Analogy) and
      PLS-DA (Partial Least Squares for Discriminant Analysis). For the black polymers
      the percentage of correct predictions was, in average, 58% taking into
      consideration the models for manufacturer and origin identification. In the case
      of white polymers, the percentage of correct predictions ranged from 72.8% (PLS
      DA) to 100% (KNN). 

PMID- 25618643
TI  - Screening and confirmation capabilities of liquid chromatography-time-of-flight
      mass spectrometry for the determination of 200 multiclass sport drugs in urine.
AB  - In this article, a screening method for the determination of 200 sport drugs in
      human urine has been developed using liquid-chromatography electrospray time-of
      flight mass spectrometry (LC-TOFMS). The chromatographic separation of the
      targeted doping agents was carried out by fast liquid chromatography using a C18
      column (4.6*50 mm) with 1.8 MUm particle size. Accurate mass measurements of the
      selected ion (typically [M+H](+) and [M-H](-)) along with retention time matching
      was used for the screening and detection of the targeted species. The proposed
      methodology comprised also a simple sample treatment stage based on solid-phase
      extraction (SPE) with polymeric cartridges. The SPE method displayed satisfactory
      recoveries rates (between 70 and 120%) for the majority of the compounds at both
      concentration levels tested (2.5 and 25 MUg L(-1)). The overall performance of
      the method was satisfactory with all 200 compounds fulfilling WADA minimum
      required performance levels (MRPLs), with limits of quantitation lower than 1 MUg
      L(-1) for 80% of the compounds, and showing an appropriate linearity (r(2)>0.99)
      in most cases. Additionally, the ability of "in-source" collision induced
      dissociation (CID) for confirmatory purposes was examined using as criterion the
      presence of two high-resolution ions with relevant abundances for unambiguous
      confirmation. This stringent criterion was fulfilled for 75% of the species using
      in-source CID fragmentation. The use of an improved approach based on CID
      performed on a dedicated collision cell without precursor ion selection (using a
      Q-TOF) provided at least two ions in all cases with the exception of 2
      aminoheptane. Finally, based on the use of diagnostic fragment ions, a workflow
      for the comprehensive screening and identification of non-targeted compounds
      (viz. compounds with no primary standards or retention time information
      available, such as metabolites) has been also examined using rat urine samples.
      The proposed screening method has proved to be effective for the analysis of
      targeted compounds, and also for the identification of metabolites, expanding
      easily the search for doping agents not only limited to specific banned parent
      compounds but also to derivate compounds with similar structure as well as
      metabolites.

PMID- 25618644
TI  - Sensitive monitoring of trace nitrophenols in water samples using multiple
      monolithic fiber solid phase microextraction and liquid chromatographic analysis.
AB  - In this work, a simple, efficient and environmentally friendly method-multiple
      monolithic fiber solid-phase microextraction (MMF-SPME) combining with high
      performance liquid chromatography (HPLC) was first established for the
      determination of six trace nitrophenols in water samples. In order to prepare MMF
      SPME, 1-allyl-3-methylimidazolium bis [(trifluoro methyl) sulfonyl] imide was co
      polymerized with ethylene dimethacrylate to get single thin fiber (0.5 mm in
      diameter). Subsequently, four thin fibers were bound together to obtain the MMF
      SPME. The effect of preparation conditions of MMF-SPME on the extraction
      performance was investigated in detail. In order to obtain the optimal extraction
      conditions of MMF-SPME for nitrophenols, several extractive parameters, including
      desorption solvent, extraction and desorption time, pH values and ionic strength
      in sample matrix were optimized. Under the optimum conditions, the linear ranges
      of 4-nitrophenol, 2,4-dinitrophenol, 5-methyl-2-nitrophenol, 5-methoxyl-2
      nitrophenol were 0.5-200 ug/L and 1.0-200 ug/L for 2-nitrophenol and 4-tertbutyl
      2-nitrophenol. The limits of detection (S/N=3) for the target analytes were 0.075
      0.27 ug/L. At the same time, excellent method reproducibility was achieved in
      terms of intra- and inter-day precisions, indicated by the RSDs of both <10.0%,
      respectively. Finally, the proposed method was successfully used to detect
      nitrophenols in different environmental water samples. Satisfactory recoveries
      ranged from 82.6% to 116% and the RSDs for reproducibility were less than 10% for
      target analytes in all real samples.

PMID- 25618645
TI  - Application of dispersive liquid-liquid microextraction coupled with vortex
      assisted hydrophobic magnetic nanoparticles based solid-phase extraction for
      determination of aflatoxin M1 in milk samples by sensitive micelle enhanced
      spectrofluorimetry.
AB  - An efficient, simple and fast low-density solvent based dispersive liquid-liquid
      microextraction (LDS-DLLME) followed by vortex-assisted dispersive solid phase
      extraction (VA-D-SPE) has been developed as a new approach for extraction and
      preconcentration of aflatoxin M1 in milk samples prior to its micelle enhanced
      spectrofluorimetic determination. In this LDS-DLLME coupled VA-D-SPE method, milk
      samples were first treated with methanol/water (80:20, v/v) after removing the
      fat layer. This solvent was directly used as the dispersing solvent in DLLME
      along with using 1-heptanol (as a low-density solvent with respect to water) as
      the extracting solvent. In VA-D-SPE approach, hydrophobic oleic acid modified
      Fe3O4 nanoparticles were used to retrieve the analyte from the DLLME step. It is
      considerably that the target of VA-D-SPE was 1-heptanol rather than the aflatoxin
      M1 directly. The main parameters affecting the efficiency of LDS-DLLME and VA-D
      SPE procedures and signal enhancement of aflatoxin M1 were investigated and
      optimized. Under the optimum conditions, the method was linear in the range from
      0.02 to 200 ug L(-1) with the correlation coefficient (R(2)) of 0.9989 and
      detection limit of 13 ng L(-1). The intra-day precision was 2.9 and 4.3% and the
      inter-day precision was 2.1 and 3.3% for concentration of 2 and 50 ug L(-1)
      respectively. The developed method was applied for extraction and
      preconcentration of AFM1 in three commercially available milk samples and the
      results were compared with the official AOAC method.

PMID- 25618646
TI  - A quick responding quartz crystal microbalance sensor array based on molecular
      imprinted polyacrylic acids coating for selective identification of aldehydes in
      body odor.
AB  - In present work, a novel quartz crystal microbalance (QCM) sensor array has been
      developed for prompt identification of primary aldehydes in human body odor.
      Molecularly imprinted polymers (MIP) are prepared using the polyacrylic acid
      (PAA) polymer matrix and three organic acids (propenoic acid, hexanoic acid and
      octanoic acid) as template molecules, and utilized as QCM surface coating layer.
      The performance of MIP films is characterized by 4-element QCM sensor array
      (three coated with MIP layers and one with pure PAA for reference) dynamic and
      static responses to target aldehydes: hexanal, heptanal, and nonanal in single,
      binary, and tertiary mixtures at distinct concentrations. The target aldehydes
      were selected subsequent to characterization of body odor samples with solid
      phase-micro extraction gas chromatography mass spectrometer (SPME-GC-MS). The
      hexanoic acid and octanoic acid imprinted PAA exhibit fast response, and better
      sensitivity, selectivity and reproducibility than the propenoic acid, and non
      imprinted PAA in array. The response time and recovery time for hexanoic acid
      imprinted PAA are obtained as 5 s and 12 s respectively to typical concentrations
      of binary and tertiary mixtures of aldehydes using the static response. Dynamic
      sensor array response matrix has been processed with principal component analysis
      (PCA) for visual, and support vector machine (SVM) classifier for quantitative
      identification of target odors. Aldehyde odors were identified successfully in
      principal component (PC) space. SVM classifier results maximum recognition rate
      79% for three classes of binary odors and 83% including single, binary, and
      tertiary odor classes in 3-fold cross validation.

PMID- 25618647
TI  - Silica-coated liposomes loaded with quantum dots as labels for multiplex
      fluorescent immunoassay.
AB  - This manuscript describes synthesis and followed application of silica-coated
      liposomes loaded with quantum dots as a perspective label for immunoaasay. The
      hollow spherical structure of liposomes makes them an attractive package material
      for encapsulation of multiple water-insoluble quantum dots and amplifying the
      analytical signal. Silica coverage ensures the stability of the loaded liposomes
      against fusion and internal leakage during storage, transporting, application and
      also provides groups for bioconugation. For the first time these nanostructures
      were employed for the sensitive multiplex immunochemical determination of two
      analytes. As a model system mycotoxins zearalenone and aflatoxin B1 were detected
      in cereals. For simplification of multiassay results' evaluation the silanized
      liposomed loaded with QDs of different colors were used. The IC50 values for the
      simultaneous determination of zearalenone and aflatoxin B1 were 16.2 and 18 ug
      kg(-1) for zearalenone and 2.2 and 2.6 ug kg(-1) for aflatoxin B1 in wheat and
      maize, respectively. As confirmatory method, liquid chromatography coupled to
      tandem mass spectrometry (LC-MS/MS) was used.

PMID- 25618648
TI  - Rapid discrimination of Klebsiella pneumoniae carbapenemase 2-producing and non
      producing Klebsiella pneumoniae strains using near-infrared spectroscopy (NIRS)
      and multivariate analysis.
AB  - Klebsiella pneumoniae Carbapenemase (KPC-2)-producing and non-producing
      Klebsiella pneumoniae (KP) have rapidly disseminated worldwide, challenging the
      diagnostics of Gram-negative infections. We evaluate the potential of a novel non
      destructive and rapid method based on Near-Infrared Spectroscopic (NIRS) and
      multivariate analysis for distinguishing KPC-2-producing and non-producing KP.
      Thirty-nine NIRS spectra (24 KPC-2-producing KP, 15 KPC-2 non-producing KP) were
      acquired; different pre-processing methods such as baseline correction,
      derivative and Savitzky-Golay smoothing were performed. A spectral region
      fingerprint was achieved after using genetic algorithm-linear discriminant
      analysis (GA-LDA) and successive projection algorithm (SPA-LDA) algorithms for
      variable selection. The variables selected were then used for discriminating the
      microorganisms.Accuracy test results including sensitivity and specificity were
      determined. Sensitivity in KPC-2 producing and non-producing KP categories was
      66.7% and 75%, respectively, using a SPA-LDA model with 66 wavenumbers. The
      resulting GA-LDA model successfully classified both microorganisms with respect
      to their "fingerprints" using only 39 wavelengths. Sensitivity in KPC-2 producing
      category was moderate(~66.7%) using a GA-LDA model. However, sensitivity in KPC-2
      non-producing category using GA-LDA accurately predicted the correct class (with
      100% accuracy). As100% accuracy was achieved, this novel approach identifies
      potential biochemical markers that may have a relation with microbial functional
      roles and means of rapid identification of KPC-2 producing and non-producing KP
      strains.

PMID- 25618649
TI  - Dual-functional Pt-on-Pd supported on reduced graphene oxide hybrids: peroxidase
      mimic activity and an enhanced electrocatalytic oxidation characteristic.
AB  - In this study, a facile hydrothermal method was developed to synthesize Pt-on-Pd
      supported on reduced graphene oxide (Pt-on-Pd/RGO) hybrids. Because of the
      synergistic effect between Pt-on-Pd and RGO, the obtained Pt-on-Pd/RGO had
      superior peroxidase-mimic activities in H2O2 reduction and TMB oxidation. The
      reaction medium was optimized and a sensing approach for H2O2 was developed with
      a linear range from 0.98 to 130.7 MUM of H2O2. In addition, the characteristic of
      electrocatalytic oxidation of methanol was investigated. The peak current density
      value, j(f), for the Pt-on-Pd/RGO hybrid (328 mA mg(Pt)(-1)) was about 1.85 fold
      higher than that of commercial Pt black (177 mA mg(Pt)(-1)) and, also, more
      durable electrocatalytic activity could be obtained. For the first time, the dual
      functional Pt-on-Pd/RGO with peroxidase-mimic activity and an enhanced
      electrocatalytic oxidation characteristic was reported.

PMID- 25618650
TI  - Anodic stripping voltammetry of gold nanoparticles at boron-doped diamond
      electrodes and its application in immunochromatographic strip tests.
AB  - Anodic stripping voltammetry (ASV) of colloidal gold-nanoparticles (AuNPs) was
      investigated at boron-doped diamond (BDD) electrodes in 50 mM HClO4. A deposition
      time of 300 s at-0.2 V (vs. Ag/AgCl) was fixed as the condition for the ASV. The
      voltammograms showed oxidation peaks that could be attributed to the oxidation of
      gold. These oxidation peaks were then investigated for potential application in
      immunochromatographic strip tests for the selective and quantitative detection of
      melamine, in which AuNPs were used as the label for the antibody of melamine.
      Linear regression of the oxidation peak currents appeared in the concentration
      range from 0.05-0.6 MUg/mL melamine standard, with an estimated LOD of 0.069
      MUg/mL and an average relative standard deviation of 8.0%. This indicated that
      the method could be considered as an alternative method for selective and
      quantitative immunochromatographic applications. The validity was examined by the
      measurements of melamine injected into milk samples, which showed good recovery
      percentages during the measurements.

PMID- 25618651
TI  - A novel dispersive micro solid phase extraction using PCX as the sorbent for the
      determination of melamine and cyromazine in milk and milk powder by UHPLC
      HRMS/MS.
AB  - A novel dispersive micro solid phase extraction (DMSPE) cleanup method based on
      the PCX sorbent (a kind of cation exchange polymer material) was applied to the
      analysis of melamine and cyromazine residues in milk and milk powder, and ultra
      high performance liquid chromatography-high resolution mass spectrometry (UHPLC
      HRMS) was used as instrument detection. Milk powder samples were first extracted
      with 1% formic acid in acetonitrile/water (1:1 v/v), and milk samples were
      cleaned up directly without any pre-extraction. Then, melamine and cyromazine in
      the extracts or milk were adsorbed to the PCX powder. Subsequently, the analytes
      in PCX sorbent were eluted with ammonium hydroxide/acetonitrile (2.5:97.5 v/v)
      through a simple unit device equipped with 1 mL syringe and 0.22 MUm nylon
      syringe filter. All the samples were analyzed by UHPLC-HRMS/MS on a Waters
      Acquity BEH HILIC column with 0.1% formic acid and 4mM ammonium formate in
      water/acetonitrile as the mobile phase with gradient elution. The matrix effect,
      recovery, and repeatability, within laboratory reproducibility, CCalpha and
      CCbeta of the DMSPE cleanup method were investigated. The proposed method
      provided a significant improvement for the determination of melamine and
      cyromazine in milk and milk powder in terms of efficient, rapid, economical, and
      miniaturized sample preparation methods, which yielded fewer matrix effects
      compared with SPE method. The established cleanup method is expected to be widely
      applied for the sample preparation of alkaline contaminants at trace levels in
      the future.

PMID- 25618652
TI  - Diffusive gradient in thin films technique for assessment of cadmium and copper
      bioaccessibility to radish (Raphanus sativus).
AB  - The aim of this study was to assess cadmium and copper uptake by radish (Raphanus
      sativus) and to test the capability of the diffusive gradient in thin films (DGT)
      technique to predict bioaccessibility of the metals for this plant. Radish plants
      were grown in pots filled with uncontaminated control and artificially
      contaminated soils differing in cadmium and copper contents. Metal concentrations
      in plants were compared with free ion metal concentrations in soil solution, and
      concentrations measured by DGT. Significant correlation was found between metal
      fluxes to plant and metal fluxes into DGT. Pearson correlation coefficient for
      cadmium was 0.994 and for copper 0.998. The obtained results showed that DGT
      offers the possibility of simple test procedure for soils and can be used as a
      physical surrogate for plant uptake. 

PMID- 25618653
TI  - 3D-nanostructured Au electrodes for the event-specific detection of MON810
      transgenic maize.
AB  - In the present work, the development of a genosensor for the event-specific
      detection of MON810 transgenic maize is proposed. Taking advantage of
      nanostructuration, a cost-effective three dimensional electrode was fabricated
      and a ternary monolayer containing a dithiol, a monothiol and the thiolated
      capture probe was optimized to minimize the unspecific signals. A sandwich format
      assay was selected as a way of precluding inefficient hybridization associated
      with stable secondary target structures. A comparison between the analytical
      performance of the Au nanostructured electrodes and commercially available screen
      printed electrodes highlighted the superior performance of the nanostructured
      ones. Finally, the genosensor was effectively applied to detect the transgenic
      sequence in real samples, showing its potential for future quantitative analysis.

PMID- 25618654
TI  - A simple dried blood spot method for therapeutic drug monitoring of the tricyclic
      antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their
      active metabolites using LC-MS/MS.
AB  - Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCAs) is
      considered useful in patients with major depressive disorder, since these drugs
      display large individual differences in clearance, and the therapeutic windows of
      these drugs are relatively small. We developed an assay for determination of
      amitriptyline (ATP), nortriptyline (NTP), imipramine (IMP), desipramine (DSP)
      clomipramine (CMP) and desmethyl-clomipramine (DCMP) in dried blood spots (DBS).
      A fast and robust LC-MS/MS method was developed and analytically validated for
      simultaneous determination of ATP, NTP, IMP, DSP, CMP, and DCMP in DBS. Six mm
      circles were punched out from DBS collected on Whatman DMPK-C paper and mixed
      with acetonitrile: methanol 1:3 containing the internal standard. The extract was
      analyzed by LC-MS/MS. Total LC-MS/MS runtime was 4.8 min. The assay was linear in
      the range 20-500 ug/L for all compounds. Overall-assay accuracy and precision
      were<20% for the lower limit of quantification (LLOQ), except for CMP (CV=22.3%),
      and <15% at other concentrations. The initial LLOQ was 20 ug/L however for CMP
      and DMCP it was increased to 40 ug/L. The blood volume per spot did not influence
      the results, but a low hematocrit (<= 30%) was associated with a >15% negative
      bias for all compounds. Punching at the perimeter of the blood spot instead of
      the center was associated with a positive bias. A good correlation was found
      between patients plasma and DBS samples of ATP, NTP and DMCP, but not for CMP. In
      addition, proportional differences were found. This LC-MS/MS method was
      analytically validated for determination of TCAs in DBS. Future validation will
      focus on the clinical application of the method.

PMID- 25618655
TI  - Competitive metal-ligand binding between CdTe quantum dots and EDTA for free Ca2+
      determination.
AB  - In this work, a fluorometric approach for the selective determination of calcium
      by using CdTe nanocrystals as chemosensors, was developed. The quantum dots
      interacted not with the metal, but with a ligand that also bonded the metal. The
      fluorescence response was modulated by the extension of the competitive metal
      ligand binding, and therefore the amount of free ligand. CdTe quantum dots (QDs)
      with different capping layers were evaluated, as the QDs surface chemistry and
      capping nature affected recognition, thus the magnitude of the ensuing
      fluorescence quenching. The developed procedure was automated by using a
      multipumping flow system. Upon optimization, thioglycolic acid (TGA) and EDTA
      were selected as capping and ligand, respectively, providing a linear working
      range for calcium concentrations between 0.80-3.20 mg L(-1), and a detection
      limit of 0.66 mg L(-1). A quenching mechanism relying on nanocrystal
      destabilization upon detachment of surface Cd by the ligand was proposed.

PMID- 25618656
TI  - A versatile, stability-indicating and high-throughput ultra-fast liquid
      chromatography method for the determination of isoflavone aglycones in soybeans,
      topical formulations, and permeation assays.
AB  - There is a growing interest in the pharmaceutical field concerning isoflavones
      topical delivery systems, especially with regard to their skin care properties
      and antiherpetic activity. In this context, the present work describes an ultra
      fast liquid chromatography method (UFLC) for determining daidzein, glycitein, and
      genistein in different matrices during the development of topical systems
      containing isoflavone aglycones (IA) obtained from soybeans. The method showed to
      be specific, precise, accurate, and linear (0.1 to 5 ug mL(-1)) for IA
      determination in soybean acid extract, IA-rich fraction obtained after the
      purification process, IA loaded-nanoemulsions, and topical hydrogel, as well as
      for permeation/retention assays in porcine skin and porcine esophageal mucosa.
      The matrix effect was determined for all complex matrices, demonstrating low
      effect during the analysis. The stability indicating UFLC method was verified by
      submitting IA to acidic, alkaline, oxidative, and thermal stress conditions, and
      no interference of degradation products was detected during analysis. Mass
      spectrometry was performed to show the main compounds produced after acid
      hydrolysis of soybeans, as well as suggest the main degradation products formed
      after stress conditions. Besides the IA, hydroxymethylfurfural and
      ethoxymethylfurfural were produced and identified after acid hydrolysis of the
      soybean extract and well separated by the UFLC method. The method's robustness
      was confirmed using the Plackett-Burman experimental design. Therefore, the new
      method affords fast IA analysis during routine processes, extract purification,
      products development, and bioanalytical assays.

PMID- 25618657
TI  - Amperometric measurements of ethanol on paper with a glucometer.
AB  - Recent advances in electrochemical analysis on filter paper exemplify the
      versatility of this substrate for high performance testing. Its low-cost, light
      weight, and environmentally friendly properties make it particularly attractive
      for applications in addressing health and environmental safety needs in low
      resource settings and developing countries. However, the main drawback to
      sensitive electrochemical testing is the use of a potentiostat, a bench-top
      instrument that is extremely expensive, thereby negating the some of the benefits
      of paper-based devices. Hence there is a need to develop paper-devices for use
      with handheld, portable device readers that can extract quantitative readouts. In
      this study, we developed a method to use micro-paper electrochemical devices, or
      uPEDs, with a glucose meter, which are used for personal monitoring of blood
      glucose levels. Ethanol was chosen as a model target analyte due to its
      importance in the global issue of road safety. uPEDs were simple in design and
      could be tested with a potentiostat. We observed that inclusion of the stabilizer
      trehalose was critical to preparing uPEDs for later analysis. In addition, an
      NAD(+)-dependent enzyme was used to impart selectivity to the biosensor, which
      also represents a class of enzymes with targets relevant to the health and food
      industry. 

PMID- 25618658
TI  - Graphene coating bonded onto stainless steel wire as a solid-phase
      microextraction fiber.
AB  - A graphene coating bonded onto stainless steel wire was fabricated and
      investigated as a solid-phase microextraction fiber. The coating was
      characterized by scanning electron microscopy and energy-dispersive X-ray
      spectrometer. The coating with rough and crinkled structure was about 1 MUm.
      These characteristics were helpful for promoting extraction. Using five n-alkanes
      (n-undecane, n-dodecane, n-tridecane, n-tetradecane and n-hexadecane) as
      analytes, the fiber was evaluated in direct-immersion mode by coupling with gas
      chromatography (GC). Through optimizing extraction and desorption conditions, a
      sensitive SPME-GC analytical method was established. SPME-GC method provided wide
      linearity range (0.2-150 MUg L(-1)) and low limits of determination (0.05-0.5 MUg
      L(-1)). It was applied to analyze rain water and a soil sample, and analytes were
      quantified in the range of 0.85-1.96 MUg L(-1) and 0.09-3.34 MUg g(-1),
      respectively. The recoveries of samples spiked at 10 MUg L(-1) were in the range
      of 90.1-120% and 80.6-94.2%, respectively. The fiber also exhibited high thermal
      and chemical stability, due to the covalent bonds between graphene coating and
      wire, and the natural resistance of graphene for thermal, acid and basic
      conditions.

PMID- 25618659
TI  - Copper-zinc alloy nanoparticle based enzyme-free superoxide radical sensing on a
      screen-printed electrode.
AB  - In this paper, amperometric enzyme-free sensors using superoxide dismutase (SOD)
      enzyme as a catalyst for the dismutation reaction of superoxides into oxygen and
      hydrogen peroxide, enabling superoxide radical detection have been described. For
      this purpose, the surfaces of screen-printed platinum electrodes have been
      modified with gelatin composites of CuO, ZnO and CuZn nanoparticles with the
      expectation of an increase in catalytic effect toward the dismutation reaction.
      SOD containing electrodes were also prepared for comparative studies in which
      glutaraldehyde was used as a cross-linker for the immobilization of SOD to the
      nanocomposite materials. Electrochemical measurements were carried out using a
      screen-printed electrochemical system that included potassiumferrocyanide
      (K4[Fe(CN)6]) and potassiumferricyanide (K3[Fe(CN)6]) as the redox probes. The
      results revealed that the enzyme-free detection method using CuZn nanoparticles
      can determine superoxide radicals with high performance compared to other
      detection methods prepared with different nanoparticles by mimicking the active
      region of superoxide dismutase enzyme. The anodic (ks(a)) and cathodic (ks(c))
      electron transfer rate constants and the anodic (alpha(a)) and cathodic
      (alpha(c)) transfer coefficients were evaluated and found to be ks(a)=6.31 s(-1)
      and alpha(a)=0.81, ks(c)=1.48 s(-1) and alpha(c)=0.19 for the gelatin-CuZn-SOD
      electrode; ks(a)=6.15 s(-1) and alpha(a)=0.79, ks(c)=1,63 s(-1) and alpha(c)=0.21
      for the enzyme-free gelatin-CuZn electrode. The enzyme-free electrode showed
      nearly 80% amperometric performance with respect to the enzyme containing
      electrode indicating the superior functionality of enzyme-free electrode for the
      detection of superoxide radicals.

PMID- 25618660
TI  - Green analytical determination of emerging pollutants in environmental waters
      using excitation-emission photoinduced fluorescence data and multivariate
      calibration.
AB  - An eco-friendly strategy for the simultaneous quantification of three emerging
      pharmaceutical contaminants is presented. The proposed analytical method, which
      involves photochemically induced fluorescence matrix data combined with second
      order chemometric analysis, was used for the determination of carbamazepine,
      ofloxacin and piroxicam in water samples of different complexity without the need
      of chromatographic separation. Excitation-emission photoinduced fluorescence
      matrices were obtained after UV irradiation, and processed with second-order
      algorithms. Only one of the tested algorithms was able to overcome the strong
      spectral overlapping among the studied pollutants and allowed their successful
      quantitation in very interferent media. The method sensitivity in superficial and
      underground water samples was enhanced by a simple solid-phase extraction with
      C18 membranes, which was successful for the extraction/preconcentration of the
      pollutants at trace levels. Detection limits in preconcentrated (1:125) real
      water samples ranged from 0.04 to 0.3 ng mL(-1). Relative prediction errors
      around 10% were achieved. The proposed strategy is significantly simpler and
      greener than liquid chromatography-mass spectrometry methods, without
      compromising the analytical quality of the results.

PMID- 25618661
TI  - Direct solid sample analysis with graphite furnace atomic absorption spectrometry
      a fast and reliable screening procedure for the determination of inorganic
      arsenic in fish and seafood.
AB  - Direct solid sample analysis with graphite furnace atomic absorption spectrometry
      (SS-GF AAS) was investigated initially with the intention of developing a method
      for the determination of total As in fish and other seafood. A mixture of 0.1%
      Pd+0.06% Mg+0.06% Triton X-100 was used as the chemical modifier, added in
      solution over the solid samples, making possible the use of pyrolysis and
      atomization temperatures of 1200  degrees C and 2400  degrees C, respectively.
      The sample mass had to be limited to 0.25 mg, as the integrated absorbance did
      not increase further with increasing sample mass. Nevertheless, the recovery of
      As from several certified reference materials was of the order of 50% lower than
      the certified value. Strong molecular absorption due to the phosphorus monoxide
      molecule (PO) was observed with high-resolution continuum source AAS (HR CS AAS),
      which, however, did not cause any spectral interference. A microwave-assisted
      digestion with HNO3/H2O2 was also investigated to solve the problem; however, the
      results obtained for several certified reference materials were statistically not
      different from those found with direct SS-GF AAS. Accurate values were obtained
      using inductively coupled plasma mass spectrometry (ICP-MS) to analyze the
      digested samples, which suggested that organic As compounds are responsible for
      the low recoveries. HPLC-ICP-MS was used to determine the arsenobetaine (AB)
      concentration. Accurate results that were not different from the certified values
      were obtained when the AB concentration was added to the As concentration found
      by SS-GF AAS for most certified reference materials (CRM) and samples, suggesting
      that SS-GF AAS could be used as a fast screening procedure for inorganic As
      determination in fish and seafood.

PMID- 25618662
TI  - Polymer monolithic methacrylate base modified with tosylated-polyethylene glycol
      monomethyl ether as a stationary phase for capillary liquid chromatography.
AB  - A polyethylene glycol (PEG) monolithic column was successfully prepared in situ
      for the separation of inorganic anions in ion exchange capillary chromatography.
      By attaching PEG-groups into the methacrylate-based polymer, the number of
      theoretical plates was improved from 1433 to 3346 plates/m (when nitrate was used
      as the analyte). The retention behavior of iodate, bromate, nitrite, bromide and
      nitrate was observed under various salt aqueous solutions. The retention was
      based on cations trapped among PEG chain and the positively charged pyridine that
      work as the anion exchange sites in the PEG monolith. The relative standard
      deviations (RSDs, for n=7) of retention time, peak height and peak area were less
      than 2.27% for all the analyte anions. The PEG monoliths showed satisfactory
      mechanical stability and did not swell or shrink significantly with swelling
      propensity value of 0.34 and 0.64 for methanol and THF, respectively. This
      stationary phase was successfully applied to the determination of these anions in
      seawater as well as public drinking water samples.

PMID- 25618663
TI  - Proposal of a procedure for the analysis of atmospheric polycyclic aromatic
      hydrocarbons in mosses.
AB  - A useful analytical procedure for the analysis of 19 polycyclic aromatic
      hydrocarbons (PAHs) in moss samples using microwave assisted extraction and
      programmed temperature vaporization-gas chromatography-tandem mass spectrometry
      (PTV-GC-MS/MS) determination is proposed. The state of art in PAHs analysis in
      mosses was reviewed. All the steps of the analysis were optimized regarding not
      only to the analytical parameters, but also the cost, the total time of analysis
      and the labour. The method was validated for one moss species used as moss
      monitor in ambient air, obtaining high recoveries (between 83-108%), low
      quantitation limits (lower than 2 ng g(-1)), good intermediate precision
      (relative standard deviation lower than 10%), uncertainties lower than 20%.
      Finally, the method was checked for other species, demonstrating its suitability
      for the analysis of different moss species. For this reason the proposed method
      can be helpful in air biomonitoring studies.

PMID- 25618664
TI  - Microextraction with polyethersulfone for bisphenol-A, alkylphenols and hormones
      determination in water samples by means of gas chromatography-mass spectrometry
      and liquid chromatography-tandem mass spectrometry analysis.
AB  - In the present work, the suitability of polyethersulfone (PES) tube was assessed
      for the simultaneous sorptive microextraction of commonly found endocrine
      disrupting compounds in natural waters such as bisphenol-A (BPA), nonylphenol
      technical mixture (NP mix), 4-tert-octylphenol (4tOP), 4-n-octylphenol (4-nOP),
      17beta-estradiol (E2) and 17alpha-ethynilestradiol (EE2). After the concentration
      of target compounds in the PES polymer, the analytes were recovered soaking the
      polymer with a suitable solvent (ethyl acetate or methanol), derivatized using
      N,O-bis(trimethylsilyl)trifluoroacetamide with 1% of trimethylchlorosilane
      (BSTFA+1% TMCS) and determined by gas chromatography-mass spectrometry (GC-MS).
      The analysis was also performed without derivatization step by means of liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Extraction parameters
      (addition of MeOH, ionic strength, extraction speed and time and desorption time)
      were evaluated and the optimum conditions were fixed as follows: 150 mL water
      samples containing a 10% (w/v) of sodium chloride and using 5 tubular PES sorbent
      fibers (1.5 cm length*0.7 mm o.d.). Equilibrium conditions were achieved after 9
      h, with absolute extraction efficiencies ranging from 27 to 56%. On the whole,
      good apparent recoveries were achieved (68-103% and 81-122% for GC-MS and LC
      MS/MS, respectively) using deuterated analogues as surrogates. Achieved
      quantification limits (LOQs) varied between 2-154 ng/L and 2-63 ng/L for all the
      compounds using GC-MS and LC-MS/MS, respectively. The effect of organic matter
      was evaluated previous to apply the final method to the analysis of estuarine and
      wastewater real samples. The comparison of both methods showed that overall, PES
      LC-MS/MS provided shorter sample preparation time and better LODs, but PES
      silylation-GC-MS allowed the simultaneous determination of all the studied
      compounds with adequate repeatability and accuracy.

PMID- 25618665
TI  - Use of multivariate statistical techniques to optimize the separation of 17
      capsinoids by ultra performance liquid chromatography using different columns.
AB  - In this work a multivariate statistical tool (Derringer and Suich optimization)
      was proposed for the separation of seventeen capsinoids (natural and synthetic)
      using the UHPLC-DAD chromatography. Capsinoids were analyzed at 280 nm. The
      variables optimized were the mobile phase (water (0.1% acetic acid as solvent A)
      and acetonitrile (0.1% as solvent B)), gradient time and flow rate. Two columns
      with different length (50 and 100 mm) were used for the chromatographic
      separation. The two columns used properly separated the seventeen capsinoids,
      however the 100 mm column length showed a better chromatographic separation with
      a shorter run time and smaller peak widths. These results provided better values
      of limit of detection and quantification for the 100 mm column length. The better
      conditions of separation with the 100 mm column length were established with:
      initial mobile phase with 41.8% of solvent B; 3.96 min of linear gradient time to
      reach 100% of solvent B; flow rate of 0.679 mL min(-1). A validation of the
      method has been done with excellent values of repeatability (RSD<1.92) and
      intermediate precision (RSD<3.92). The developed method has been applied to real
      samples. Capsiate has been identified and quantified in some varieties of
      peppers.

PMID- 25618666
TI  - Paper-based microfluidic sensing device for label-free immunoassay demonstrated
      by biotin-avidin binding interaction.
AB  - Efficient diagnosis is very important for the prevention and treatment of
      diseases. Rapid disease screening in ambulatory environment is one of the most
      pressing needs for disease control. Despite there are many methods to detect the
      results of immunoassays, quantitative measurement for rapid disease screening is
      still a great challenge for point-of-care applications. In this study, a
      fabrication method for depositing carbon nanotube bundles has been successfully
      developed for realization of functional paper-based microfluidic sensing device.
      Quantitative detection of label-free immunoassay, i.e., biotin-avidin binding
      interaction, was demonstrated by direct measurement of the current change of the
      biosensor after single application of the target analyte. Sensitivity of 0.33
      MUA/ng mL(-1) and minimal detectable analyte concentration of 25 ng/mL were
      achieved. The time necessary for the detection was 500 s which is a large
      reduction compared with the conventional immunoassay. Such paper-based biosensor
      has the benefits of portability, fast response, simple operation, and low cost
      and has the potential for the development of rapid disease screening devices.

PMID- 25618667
TI  - Assembly-line manipulation of droplets in microfluidic platform for fluorescence
      encoding and simultaneous multiplexed DNA detection.
AB  - In this article, a new mode of droplets manipulation is presented and applied for
      simultaneous multiplexed DNA detection. We call this droplets manipulation,
      "assembly-line manipulation of droplets (ALMD)". Firstly, multiple droplets
      containing the same target mixtures are generated in the microchannel, and then
      fused with later generated different droplets containing corresponding probes,
      respectively. Finally, all the fused droplets were fluorescence imaged on-line
      and real-time. The successful implementation of droplets fluorescence encoding
      based on ALMD shows the reproducibility and accuracy of this manipulation mode.
      As a proof-of-concept application, the simultaneous multiplexed DNA detection was
      carried out through the model of human immunodeficiency virus (HIV) gene sequence
      and variola virus (small pox, VV) gene sequence based on ALMD in the microfluidic
      system. It is proved that this method achieves simultaneous multiplexed DNA
      measurements with a significantly time-saving way and without different dye
      labelled probes or complex operation procedures. In addition, it reveals the
      possibility of high-throughput biosensing with simple chip design and detection
      equipment. 

PMID- 25618668
TI  - Laser-induced breakdown spectroscopy (LIBS) combined with hyperspectral imaging
      for the evaluation of printed circuit board composition.
AB  - In this study, laser-induced breakdown spectroscopy (LIBS) was combined with
      chemometric strategies (PCA, Principal Component Analysis) and scanning electron
      microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS) to investigate the
      metal composition of a printed circuit board (PCB) sample from a mobile phone.
      Scanning electron microscopy-EDS was used for two main reasons: it was possible
      at the same time to visualize the sample surface, craters (made by the laser
      pulses) and also the chemical composition of the samples. A 30 mm*40 mm area of
      the mobile phone PCB sample, which was manufactured in 2011, was investigated. In
      this case, a matrix with 30 rows and 40 columns (1200 points) was analyzed, and
      10 pulses were performed at each point. A total of 12,000 emission spectra were
      recorded in the wavelength range from 186 to 1040 nm. After an initial
      exploratory investigation using PCA, 18 emission lines were selected
      (representing the elements Al, Au, Ba, Ca, Co, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Sb,
      Si, Sn, Ti and Zn) and then normalized by the relative intensities, and a new PCA
      was calculated with the autoscaled data. For example, Au and Si were mainly
      observed in the superficial electrical contacts and in the bulk of the PCB,
      respectively. A second sample (a mouse PCB) was also analyzed and Pb (emission
      lines 357.273, 363.956, 368.346, 373.994 and 405.780 nm) was identified in the
      solders. In addition, this element was determined using FAAS (flame atomic
      absorption spectrometry) and the Pb concentration was around 25% (w/w). This
      study opens the possibility for improved recycling processes and the chemical
      investigation of solid samples measuring a few millimeters in dimension without
      sample preparation.

PMID- 25618669
TI  - Roles of chemical metrology in electronics industry and associated environment in
      Korea: a tutorial.
AB  - Chemical metrology is gaining importance in electronics industry that
      manufactures semiconductors, electronic displays, and microelectronics. Extensive
      and growing needs from this industry have raised the significance of accurate
      measurements of the amount of substances and material properties. For the first
      time, this paper presents information on how chemical metrology is being applied
      to meet a variety of needs in the aspects of quality control of electronics
      products and environmental regulations closely associated with electronics
      industry. For a better understanding of the roles of the chemical metrology
      within electronics industry, the recent research activities and results in
      chemical metrology are presented using typical examples in Korea where electronic
      industry is leading a national economy. Particular attention is paid to the
      applications of chemical metrology for advancing emerging electronics technology
      developments. Such examples are a novel technique for the accurate quantification
      of gas composition at nano-liter levels within a MEMS package, the surface
      chemical analysis of a semiconductor device. Typical metrological tools are also
      presented for the development of certified reference materials for fluorinated
      greenhouse gases and proficiency testing schemes for heavy metals and chlorinated
      toxic gas in order to cope properly with environmental issues within electronics
      industry. In addition, a recent technique is presented for the accurate
      measurement of the destruction and removal efficiency of a typical greenhouse gas
      scrubber. 

PMID- 25618670
TI  - Magnetic solid phase extraction for the determination of trace antimony species
      in water by inductively coupled plasma mass spectrometry.
AB  - A new magnetic solid phase extraction (MSPE) method using octyl-immobilized
      silica-coated magnetic Fe3O4 (C8-Fe3O4@SiO2) nanoparticles as the MSPE adsorbent
      combined with inductively coupled plasma mass spectrometry (ICP-MS) has been
      developed for speciation analysis of Sb(III) and Sb(V). At pH 5.0, Sb(III) forms
      a hydrophobic complex with ammonium pyrrolidine dithiocarbamate (APDC) and is
      retained on C8-Fe3O4@SiO2 nanoparticles, whereas Sb(V) remains as free species in
      aqueous solution. At pH 2.0, both Sb species (total Sb) form hydrophobic APDC
      complexes, being retained on the adsorbent. Thus, sensitive speciation analysis
      of Sb(III) and Sb(V) could be achieved by selective SPE of either Sb(III) or
      total Sb under different pH on C8-Fe3O4@SiO2 nanoparticles. The experimental
      parameters, such as pH of solution, concentration of APDC, eluent type and sample
      volume were optimized in detail. The limits of detection (LOD, 3delta, n=10) of
      this MSPE method was 0.001 MUg L(-1) and 0.004 MUg L(-1), respectively, for
      Sb(III) and Sb(V). The precision of the method (Relative standard deviation, RSD,
      n=6) for Sb(III) and Sb(V) at 1.0 MUg L(-1) was 3.4% and 4.6%, respectively. In
      order to verify the accuracy of the method, certified reference material (GSB 07
      1376-2001) of environmental water was analyzed and the result obtained was in
      good agreement with the certified values. This proposed method is simple,
      accurate and sensitive, and can be applied to the speciation of Sb(III) and Sb(V)
      in environmental waters without any pre-reduction or pre-oxidation operation.

PMID- 25618671
TI  - G-quadruplex DNA/protoporphyrin IX-based synergistic platform for targeted
      photodynamic cancer therapy.
AB  - Photodynamic therapy (PDT) is an emerging technique to induce cancer cell death.
      However, the tumor specificity, cellular uptake and biodistribution of many
      photosensitizers urgently need to be improved. In this regard, we show here that
      the integrated nanoassemblies based on G-quadruplex DNAs (GQDs)/protoporphyrin IX
      (PPIX) can serve as a synergistic platform for targeted high-performance PDT. In
      the nanoassemblies, GQDs function as carriers of sensitiser PPIX and confers the
      system cancer cell targeting ability. After nucleolin-mediated efficient binding
      and cellular uptake of GQDs/PPIX assemblies, the strong red fluorescence of
      GQDs/PPIX complex provides a powerful tool for biological imaging. Moreover, the
      reactive oxygen species (ROS) generated by GQDs/PPIX under light illumination can
      effectively kill cancer cells. The present approach is simply composed by DNA and
      photosensitizers, thereby avoiding any complicated and time-consuming covalent
      modification or chemical labeling procedure. 

PMID- 25618672
TI  - Sandwich-type electrochemical immunosensor using dumbbell-like nanoparticles for
      the determination of gastric cancer biomarker CA72-4.
AB  - A novel and sensitive nonenzymatic sandwich-type electrochemical immunosensor for
      the detection of gastric cancer biomarker CA72-4 was fabricated using dumbbell
      like PtPd-Fe3O4 nanoparticles (NPs) as a novel kind of label. The signal
      amplification strategy, using the synergetic effect present in PtPd-Fe3O4 to
      increase the reduction ability of the NPs toward H2O2, improved the sensitivity
      of the immunosensor. The immunosensor was constructed by modifying glassy carbon
      electrode with reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) for
      effective immobilization of primary anti-CA72-4 antibody (Ab1). Secondary anti
      CA72-4 antibody (Ab2) was adsorbed onto the PtPd-Fe3O4 NPs. The proposed
      immunosensor displayed a wide linear range (0.001-10 U/mL) with the low detection
      limit (0.0003 U/mL). The immunosensor was evaluated for serum samples, receiving
      satisfactory results. Therefore, the immunosensor possesses excellent clinical
      value in cancer screening as well as convenient point-of-care diagnostics.

PMID- 25618673
TI  - Highly selective and automated online SPE LC-MS3 method for determination of
      cortisol and cortisone in human hair as biomarker for stress related diseases.
AB  - Hair analysis has been increasingly used to establish long-term biomarkers of
      exposure to both endogenous and exogenous substances, with a special emphasis on
      steroidal hormones. Hair cortisol and cortisone have been associated to
      physiological and psychological strains, anxiety and depression. Hair is a very
      complex matrix, which might jeopardize analyte detection at low concentrations. A
      new, highly selective and sensitive method based on fragments of second order,
      MS(3) (MS/MS/MS), was developed and validated for the analysis of hair cortisol
      and cortisone. An online solid phase extraction was performed on a C8 restricted
      access material (RAM) phase following by separation on a reversed-phase C18
      column using methanol and 0.02% ammonium hydroxide as mobile phase. The developed
      method required minimal sample preparation and the injection of only 50 uL of
      sample leading to a LOQ of 2 pg mg(-1). Good linear responses were observed in
      the range 2-200 pg mg(-1) (R(2)>0.99) and extraction recoveries ranged between 77
      125% and 70-123% for cortisol and cortisone, respectively. Intra- and inter-assay
      coefficients of variation were between 1.4 and 14%. In order to evaluate the
      applicability of the method, preliminary tests (N=33) were conducted in 3 cm hair
      samples (close to scalp) of healthy volunteers with an age range of 4-63. Average
      concentrations in hair were 12.7+/-14 pg mg(-1) and 41.6+/-42 pg mg(-1) for
      cortisol and cortisone, respectively. Further investigations on cortisol and
      cortisone as biomarkers for chronic psychological strain will be assessed as a
      next step.

PMID- 25618674
TI  - ZnS:Mn nanoparticles functionalized by PAMAM-OH dendrimer based fluorescence
      ratiometric probe for cadmium.
AB  - We report a nanocomposite of ZnS:Mn quantum dots and a third generation PAMAM-OH
      dendrimer (ZnS:Mn@PAMAM-OH(G=3)) which was rationalized to be used as ratiometric
      nanosensor for Cd(2+) in aqueous solution. The nanoparticles exhibited a bright
      yellow-orange emission with peaks at 448 and 595 nm. The structure of ZnS:Mn was
      not changed after coupling with PAMAM-OH, which was evidenced by the analysis of
      the emission spectra of the compounds. The results confirm that the prepared
      fluorescence nanoparticles could selectively detect Cd(2+) in aqueous solution
      with a limit of detection of 24.34 MUM and RSD 4.07%, obtained by using the ratio
      I448/I595. The method was applied to different water samples.

PMID- 25618675
TI  - Enantioselective determination of representative profens in wastewater by a
      single-step sample treatment and chiral liquid chromatography-tandem mass
      spectrometry.
AB  - This manuscript describes, for the first time, the simultaneous enantioselective
      determination of ibuprofen, naproxen and ketoprofen in wastewater based on liquid
      chromatography tandem mass spectrometry (LC-MS/MS). The method uses a single-step
      sample treatment based on microextraction with a supramolecular solvent made up
      of hexagonal inverted aggregates of decanoic acid, formed in situ in the
      wastewater sample through a spontaneous self-assembly process. Microextraction of
      profens was optimized and the analytical method validated. Isotopically labeled
      internal standards were used to compensate for both matrix interferences and
      recoveries. Apparent recoveries for the six enantiomers in influent and effluent
      wastewater samples were in the interval 97-103%. Low method detection limits
      (MDLs) were obtained (0.5-1.2 ng L(-1)) as a result of the high concentration
      factors achieved in the microextraction process (i.e. actual concentration
      factors 469-736). No analyte derivatization or evaporation of extracts, as it is
      required with GC-MS, was necessary. Relative standard deviations for enantiomers
      in wastewater were always below 8%. The method was applied to the determination
      of the concentrations and enantiomeric fractions of the targeted analytes in
      influents and effluents from three wastewater treatment plants. All the values
      found for profen enantiomers were consistent with those previously reported and
      confirmed again the suitability of using the enantiomeric fraction of ibuprofen
      as an indicator of the discharge of untreated or poorly treated wastewaters. Both
      the analytical and operational features of this method make it applicable to the
      assessment of the enantiomeric fate of profens in the environment.

PMID- 25618676
TI  - Development of a ratiometric fluorescent urea biosensor based on the urease
      immobilized onto the oxazine 170 perchlorate-ethyl cellulose membrane.
AB  - In this work, the oxazine 170 perchlorate (O17)-ethyl cellulose (EC) membrane was
      successfully applied in the fabrication of a urea-sensing membrane. The urea
      sensing membrane was a double layer consisting of the O17-EC membrane and a layer
      of the enzyme urease entrapped into EC matrix. The sensing principle of urea was
      based on the hydrolysis reaction of urea under the catalysis of the urease to
      produce ammonia in water and also on the binding of ammonia with the dye O17 to
      create the shift in the emission wavelength from lambda(em)=630 nm to
      lambda(em)=565 nm. The data collected from the ratio of the fluorescence
      intensities at lambda(em)=630 nm and lambda(em)=565 nm was proportional to urea
      concentration. The urea-sensing membrane with the ratiometric method was used to
      measure the concentrations of urea in the range of 0.01-0.1 M with a limit of
      detection (LOD) of 0.027 mM and 0.1-1.0 M with LOD of 0.224 mM. It showed fast
      response time, high reversibility and long-term stability in this concentration
      range. The recovery percentage of urea concentrations of the urea-sensing
      membrane for two kinds of biological urine solutions (BU1, BU2) was around 85
      118%. The measured results were in good agreement with standard urea
      concentrations in the range of 0.06 M to 1.0 M.

PMID- 25618677
TI  - Molecularly imprinted sol-gel nanofibers based solid phase microextraction
      coupled on-line with high performance liquid chromatography for selective
      determination of acesulfame.
AB  - Sol-gel based molecularly imprinted polymer (MIP) nanofiber was successfully
      fabricated by electrospinning technique on the surface of a stainless steel bar.
      The manufactured tool was applied for on-line selective solid phase
      microextraction (SPME) and determination of acesulfame (ACF) as an artificial
      sweetener with high performance liquid chromatography (HPLC). The selective
      ability of method for the extraction of ACF was investigated in the presence of
      some selected sweeteners such as saccharine (SCH), aspartame (ASP) and caffeine
      (CAF). Electrospinning of MIP sol-gel solution on the stainless steel bar
      provided an unbreakable sorbent with high thermal, mechanical, and chemical
      stability. Moreover, application of the MIP-SPME tool revealed a unique approach
      for the selective microextraction of the analyte in beverage samples. In this
      work, 3-(triethoxysilyl)-propylamine (TMSPA) was chosen as a precursor due to its
      ability to imprint the analyte by hydrogen bonding, Van der Walls, and dipole
      dipole interactions. Nylon 6 was also added as a backbone and support for the
      precursor in which sol could greatly growth during the sol-gel process and makes
      the solution electrospinable. Various effective parameters in the extraction
      efficiency of the MIP-SPME tool such as loading time, flow rate, desorption time,
      selectivity, and the sample volume were evaluated. The linearity for the ACF in
      beverage sample was in the range of 0.78-100.5 ng mL(-1). Limit of detection
      (LOD) and quantification (LOQ) were 0.23 and 0.78 ng mL(-1) respectively. The RSD
      values (n=5) were all below 3.5%at the 20 ng mL(-1) level.

PMID- 25618678
TI  - Sensing and inhibition of amyloid-beta based on the simple luminescent aptamer
      ruthenium complex system.
AB  - Aggregation of amyloid-beta (Abeta) peptide has been known to be pathologically
      associated with Alzheimer and dementia diseases. Amyloid-beta fibrils serve as an
      important target for the drugs development and diagnosis of neurodegenerative
      diseases. Herein, we report a new [Ru(dmbpy)(dcbpy)dppz)] complex (dmbpy; 4,4'
      dimethyl-2,2'-bipyridine, dcbpy; 4,4'-dicorboxy-2,2'-bipyridine, dppz;
      dipyridophenazine) intercalated aptamer based recognition of amyloid-beta.
      Interestingly, aforementioned Ru(II) complex shows weak luminescence intensity in
      the aqueous medium but it shows strong luminescence intensity in the presence of
      RNA aptamer. Upon addition of amyloid-beta monomers, the luminescence intensity
      of Ru(II) complex is reduced due to the strong interaction of aptamer with
      amyloid-beta monomer/small oligomers. Furthermore, present study implies that our
      system has ability to inhibit the formation of amyloid-beta fibrils, which is
      confirmed from the AFM morphological structures in the absence and presence of
      aptamer. This work may contribute the rapid diagnosis and inhibition of amyloid
      beta aggregation in the clinical applications. 

PMID- 25618679
TI  - Determination of guanine and adenine by high-performance liquid chromatography
      with a self-fabricated wall-jet/thin-layer electrochemical detector at a glassy
      carbon electrode.
AB  - A sensitive wall-jet/thin-layer amperometric electrochemical detector (ECD)
      coupled to high-performance liquid chromatography (HPLC) was developed for
      simultaneous determination of guanine (G) and adenine (A). The analytes were
      detected at a glassy carbon electrode (GCE) and the HPLC-ECD calibration curves
      showed good linearity (R(2)>0.997) under optimized conditions. Limits of
      detection for G and A are 0.6 nM and 1.4 nM (S/N=3), respectively, which are
      lower than those obtained with an UV-vis detector and a commercial
      electrochemical detector. We have successfully applied this HPLC-ECD to assess
      the contents of G and A in hydrochloric acid-digested calf thymus double-stranded
      DNA. In addition, we compared in detail the analysis of G and A by cyclic
      voltammetry (CV) and by the HPLC-ECD system on both bare GCE and electroreduced
      graphene oxide (ERGO) modified GCE. We found that the adsorption of G and A on
      the electrode surfaces can vary their anodic CV peaks and the competitive
      adsorption of G and A on the limited sites of the electrode surfaces can cause
      crosstalk effects on their anodic CV peak signals, but the HPLC-ECD system is
      insensitive to such electrode-adsorption and can give more reliable analytical
      results.

PMID- 25618680
TI  - Determination and speciation of trace and ultratrace selenium ions by energy
      dispersive X-ray fluorescence spectrometry using graphene as solid adsorbent in
      dispersive micro-solid phase extraction.
AB  - A dispersive micro-solid phase extraction (DMSPE) with graphene as a solid
      adsorbent and ammonium pyrrolidinedithiocarbamate (APDC) as a chelating agent was
      proposed for speciation and detemination of inorganic selenium by the energy
      dispersive X-ray fluorescence spectrometry (EDXRF). In developed DMSPE, graphene
      particles are dispersed throughout the analyzed solution, therefore reaction
      between Se(IV)-APDC complexes and graphene nanoparticles occurs immediately. The
      concentration of Se(VI) is calculated as the difference between the concentration
      of selenite after and before prereduction of selenate. A central composite face
      centered design with 3 center points was performed in order to optimize
      conditions and to study the effect of four variables (pH of the sample,
      concentration of APDC, concentration of Triton-X-100, and sample volume). The
      best results were obtained when suspension consisting of 200 ug of graphene
      nanosheets, 1.2 mg of APDC and 0.06 mg of Triton-X-100 was rapidly injected to
      the 50 mL of the analyzed solution. Under optimized conditions Se ions can be
      determined with a very good recovery (97.7+/-5.0% and 99.2+/-6.6% for Se(IV) and
      Se(VI), respectively) and precision (RSD=5.1-6.6%). Proposed DMSPE/EDXRF
      procedure allowed to obtain low detection limits (0.032 ng mL(-1)) and high
      enrichment factor (1013+/-15). The proposed methodology was successfully applied
      for the determination of Se in mineral, tap, lake and sea water samples as well
      as in biological materials (Lobster Hepatopancreas and Pig Kidney).

PMID- 25618681
TI  - Integrated microwave processing system for the extraction of organophosphorus
      pesticides in fresh vegetables.
AB  - A simple and efficient integrated microwave processing system (IMPS) was firstly
      assembled and validated for the extraction of organophosphorus pesticides in
      fresh vegetables. Two processes under microwave irradiation, dynamic microwave
      assisted extraction (DMAE) and microwave-accelerated solvent elution (MASE), were
      integrated for simplifying the pretreatment of the sample. Extraction,
      separation, enrichment and elution were finished in a simple step. The
      organophosphorus pesticides were extracted from the fresh vegetables into hexane
      with DMAE, and then the extract was directly introduced into the enrichment
      column packed with active carbon fiber (ACF). Subsequently, the organophosphorus
      pesticides trapped on the ACF were eluted with ethyl acetate under microwave
      irradiation. No further filtration or cleanup was required before analysis of the
      eluate by gas chromatography-mass spectrometry. Some experimental parameters
      affecting extraction efficiency were investigated and optimized, such as
      microwave output power, kind and volume of extraction solvent, extraction time,
      amount of sorbent, elution microwave power, kind and volume of elution solvent,
      elution solvent flow rate. Under the optimized conditions, the recoveries were in
      the range of 71.5-105.2%, and the relative standard deviations were lower than
      11.6%. The experiment results prove that the present method is a simple and
      effective sample preparation method for the determination of pesticides in solid
      samples. 

PMID- 25618682
TI  - Chiral on-line solid phase extraction coupled to liquid chromatography-tandem
      mass spectrometry assay for quantification of (R) and (S) enantiomers of
      methadone and its main metabolite in plasma.
AB  - The authors aimed at developing a liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method with online extraction to determine (R)- and (S)- methadone
      enantiomers and its main metabolite 2-ethylidine-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP) in plasma. The analysis combined straightforward
      sample preparation, consisting of protein precipitation with acetonitrile, and an
      online enrichment by a flush/back-flush cycle before the second dimension
      chromatography. Using D3-deuterated internal standards allows overcoming
      significant relative matrix effect. Our method was linear up to 2000 ng/mL. This
      simple sample preparation provides sensitive (the limit of quantitation is 25
      ng/mL for (R,S)-methadone and EDDP and 12.5 ng/mL for (R)- and (S)- methadone),
      accurate and precise (the intra-day and inter-day imprecision and inaccuracy are
      lower than 15%) quantification of the plasma concentration of these drugs. We
      have developed a reliable LC-MS/MS method for both routine therapeutic drug
      monitoring and pharmacokinetics studies and for toxicology analysis in the
      setting of methadone treatment or intoxication.

PMID- 25618683
TI  - Fourier transform infrared spectroscopy and near infrared spectroscopy for the
      quantification of defects in roasted coffees.
AB  - The coffee strip-picking harvesting method, preferred in Brazil, results in high
      percentages of immature and overripe beans, as the fruits in a single tree branch
      do not reach ripeness at the same time. This practice, together with
      inappropriate processing and storage conditions, contribute to the production of
      high amounts of defective coffee beans in Brazil, which upon roasting will impart
      negative sensory aspects to the beverage. Therefore, the development of
      analytical methodologies that will enable the discrimination and quantification
      of defective and non-defective coffees after roasting is rather desirable. Given
      that infrared spectroscopy has been successfully applied to coffee analysis, the
      objective of this work was to evaluate and to compare the performances of Fourier
      transform infrared (FTIR) and near infrared (NIR) spectroscopies for the
      quantification of defective beans in roasted coffees. Defective and non-defective
      Arabica coffee beans were manually selected, roasted, ground and sieved. Mixtures
      of defective and non-defective roasted and ground coffees were produced and
      analyzed, with % defects ranging from 0% to 30%. FTIR and NIR spectra were
      recorded, respectively, within a range of 3100-800 cm(-1) and 1200-2400 nm and
      submitted to mathematical processing. Quantitative models were developed by
      partial least squares regression (PLSR). Excellent predictive results were
      obtained indicating that defective coffees could be satisfactorily quantified.
      The correlation coefficients and the root mean squared errors of validation for
      the FTIR and NIR models developed to quantify the amount of defective roasted
      coffees mixed with non-defective ones were, respectively, as high as 0.891 and as
      low as 0.032, and as high as 0.953 and as low as 0.026. A comparison between the
      two techniques indicated that NIR provided more robust models.

PMID- 25618684
TI  - Magnetic solid phase extraction of gemfibrozil from human serum and
      pharmaceutical wastewater samples utilizing a beta-cyclodextrin grafted graphene
      oxide-magnetite nano-hybrid.
AB  - A magnetic solid phase extraction method based on beta-cyclodextrin (beta-CD)
      grafted graphene oxide (GO)/magnetite (Fe3O4) nano-hybrid as an innovative
      adsorbent was developed for the separation and pre-concentration of gemfibrozil
      prior to its determination by spectrofluorometry. The as-prepared beta
      CD/GO/Fe3O4 nano-hybrid possesses the magnetism property of Fe3O4 nano-particles
      that makes it easily manipulated by an external magnetic field. On the other
      hand, the surface modification of GO by beta-CD leads to selective separation of
      the target analyte from sample matrices. The structure and morphology of the
      synthesized adsorbent were characterized using powder X-ray diffraction, Fourier
      transform infrared spectroscopy, and field emission scanning electron microscopy.
      The experimental factors affecting the extraction/pre-concentration and
      determination of the analyte were investigated and optimized. Under the optimized
      experimental conditions, the calibration graph was linear in the range between 10
      and 5000 pg mL(-1) with a correlation coefficient of 0.9989. The limit of
      detection and enrichment factor for gemfibrozil were 3 pg mL(-1) and 100,
      respectively. The maximum sorption capacity of the adsorbent for gemfibrozil was
      49.8 mg g(-1). The method was successfully applied to monitoring gemfibrozil in
      human serum and pharmaceutical wastewaters samples with recoveries in the range
      of 96.0-104.0% for the spiked samples.

PMID- 25618685
TI  - Validation of SPME-GCMS method for the analysis of virgin olive oil volatiles
      responsible for sensory defects.
AB  - Volatile compounds are responsible for the aroma of virgin olive oil and also for
      its quality. The high number and different nature of volatile compounds drive to
      the need of a reliable analytical method that allows their proper quantification
      to explain the standard method of panel test. Although there are some analytical
      solutions available, they have not been validated and the regulatory bodies are
      reluctant to adopt them since they can be subjected to unknown errors. In this
      regards, the European Union has encouraged the validation of these analytical
      tools through the research program Horizon2020, which involves gaining knowledge
      from the analytical properties of the chemical methods for sensory assessment.
      This work is focused on the analytical validation of the methodology used to
      determine the actual concentration of volatiles in virgin olive oils when
      applying SPME-GCMS. The validation process includes the calibration curves for 29
      volatile compounds responsible for the most common sensory perceptions in virgin
      olive oils, the determination of their working ranges with linear response, the
      detection and quantification limits, the sensitivity, the accuracy estimated as
      trueness and precision and the selectivity. Sixty-seven percent of the compounds
      presented a relative standard deviation in repeatability lower than 10%, and this
      percentage rises to 95% in lampante virgin olive oils. The accuracy was
      established in 97% of the studied volatile compounds. Finally, an empirical
      example of the ability of the method to discriminate virgin olive oils of
      different categories (extra virgin, virgin, ordinary and lampante) by the
      quantification of their volatiles is provided. 

PMID- 25618686
TI  - Protocols for finding the most orthogonal dimensions for two-dimensional high
      performance liquid chromatography.
AB  - The selection of two high performance liquid chromatography (HPLC) columns with
      vastly different retention mechanisms is vital for performing effective two
      dimensional (2D-) HPLC. This paper reports on a systematic method to select a
      pair of HPLC columns that provide the most different separations for a given
      sample. This was completed with the aid of a HPLC simulator that predicted
      retention profiles on the basis of real experimental data, which is difficult
      when the contents of sample matrices are largely-or completely-unknown. Peaks
      from the same compounds must first be matched between chromatograms to compare
      the retention profiles and optimised 2D-HPLC column selection. In this work, two
      methods of matching peaks between chromatograms were explored and an optimal pair
      of chromatography columns was selected for 2D-HPLC. First, a series of 17
      antioxidants were selected as an analogue for a coffee extract. The predicted
      orthogonality of the standards was 39%, according to the fractional surface
      coverage 'bins' method, which was close to the actual space utilisation of the
      standard mixture, 44%. Moreover, the orthogonality for the 2D-HPLC of coffee
      matched the predicted value of 38%. The second method employed a complex sample
      matrix of urine to optimise the column selections. Seven peaks were confidently
      matched between chromatograms by comparing relative peak areas of two detection
      strategies: UV absorbance and potassium permanganate chemiluminescence. It was
      found that the optimal combinations had an orthogonality of 35% while the actual
      value was closer to 30%. 

PMID- 25618687
TI  - Use of green coating (cork) in solid-phase microextraction for the determination
      of organochlorine pesticides in water by gas chromatography-electron capture
      detection.
AB  - A novel method for the determination of organochlorine pesticides in water
      samples with extraction using cork fiber and analysis by gas chromatography with
      electron capture detector was developed. Also, the procedure to extract these
      pesticides with DVB/Car/PDMS fiber was optimized. The optimization of the
      variables involved in the extraction of organochlorine pesticides using the
      aforementioned fibers was carried out by multivariate design. The optimum
      extraction conditions were sample temperature 75  degrees C, extraction time 60
      min and sodium chloride concentration 10% for the cork fiber and sample
      temperature 50  degrees C and extraction time 60 min (without salt) for the
      DVB/Car/PDMS fiber. The quantification limits for the two fibers varied between
      1.0 and 10.0 ng L(-1). The linear correlation coefficients were >0.98 for both
      fibers. The method applied with the use of the cork fiber provided recovery
      values between 60.3 and 112.7 and RSD<=25.5 (n=3). The extraction efficiency
      values for the cork and DVB/Car/PDMS fibers were similar. The results show that
      cork is a promising alternative as a coating for SPME.

PMID- 25618688
TI  - Validation and application of micro flow liquid chromatography-tandem mass
      spectrometry for the determination of pesticide residues in fruit jams.
AB  - In this study, a very sensitive method was validated to determine pesticides
      residues in fruit jams using micro flow liquid chromatography-tandem mass
      spectrometry (uLC-MS/MS). A slurry of the fruit jams and water was prepared to
      yield homogeneous samples. Because of the high sensitivity achieved with the uLC
      MS/MS equipment and to minimize matrix effects, the QuEChERS extracts were
      diluted 30-fold before the analysis. The validation was performed analyzing
      spiked samples at 9 and 45 ug kg(-1) (n=5). The method met validation criteria of
      70-120% recovery and RSD<=20% for 92% of the 107 pesticides evaluated. The
      reporting limit (RL) was 9 and 45 ug kg(-1) for respectively 66% and 26% of the
      analytes, 5% of the compounds did not fulfill the requirements for validation and
      3% were not detected at the studied concentrations. The validated method was
      applied to the analysis of 51 different fruit jam samples from Brazil and Spain
      and pesticide residues were detected in 41 samples, 26 of which contained at
      least one pesticide at concentration >10 ug kg(-1).

PMID- 25618689
TI  - One-step synthesis of sub-2 MUm vinyl functionalized silica sphere as stationary
      phase for liquid chromatography.
AB  - Vinyl-functionalized silica spheres (VFSS) were synthesized through the one-step
      method. The effects of reactant ratio, temperature, reaction time and ammonium
      hydroxide dripping speed were investigated. The diameter of the spheres reached
      sub-2 MUm magnitude by controlling the reaction conditions, which is suitable for
      high performance liquid chromatography (HPLC) packing material. The vinyl groups
      in the silica spheres were further successfully modified by octadecyl (C18)
      groups through a "thiol-ene" click reaction. Raw VFSS and C18modified VFSS (C
      VFSS) were used as HPLC stationary phases to separate benzene homologs (benzene,
      toluene, and meta-xylene) and nonpolar compounds with different ring contents
      (benzene, phenantherene and fluoranthene). Both VFSS and C-VFSS exhibited
      hydrophobic retention behavior. Additionally, vinyl groups in the silica spheres
      may offer a pi-pi electron-donor-acceptor (EDA) retention mechanism for
      chromatographic separation.

PMID- 25618690
TI  - Development and application of tetrabromobisphenol A imprinted electrochemical
      sensor based on graphene/carbon nanotubes three-dimensional nanocomposites
      modified carbon electrode.
AB  - A novel imprinted electrochemical sensor based on graphene/carbon nanotubes three
      dimensional (3D) nanocomposites modified carbon electrode was developed for the
      determination of tetrabromobisphenol A. The imprinted film was prepared by one
      step electrodeposition technique with pyrrole as the functional monomer and
      tetrabromobisphenol A as the template molecule. The imprinted sensor was used for
      the determination of tetrabromobisphenol A with differential pulse voltammetry. A
      linear relationship between the response currents and the negative logarithm of
      tetrabromobisphenol A concentrations was obtained in the concentrations range of
      1.0*10(-11)-1.0*10(-8) mol L(-1) with a detection limit of 3.7*10(-12) mol L(-1)
      (S/N=3). The proposed imprinted sensor showed excellent selectivity towards
      tetrabromobisphenol A. With good reproducibility and stability, the imprinted
      electrochemical sensor was used to detect tetrabromobisphenol A in fish samples
      successfully with the recoveries of 93.3-107.7%.

PMID- 25618692
TI  - "Signal on" electrochemiluminescence pentachlorophenol sensor based on luminol
      MWCNTs@graphene oxide nanoribbons system.
AB  - A "signal on" electrochemiluminescence (ECL) sensor for pentachlorophenol (PCP)
      detection was constructed based on the amplified ECL of luminol at a multiwalled
      carbon nanotubes@graphene oxide nanoribbons (MWCNTs@GONRs) modified electrode.
      Due to the good electrocatalytic activity of MWCNTs@GONRs toward luminol system,
      the oxidation peak current of luminol at the MWCNTs@GONRs modified electrode was
      enhanced for ~6-fold than that of the bare electrode; and the ECL intensity of
      luminol was amplified for ~5.3-fold correspondingly. Furthermore, the amplified
      ECL signal of luminol was linear with the concentration of PCP in the range
      between 2 pg mL(-1) and 10 ng mL(-1) with a detection limit of 0.7 pg mL(-1)
      (S/N=3). With the merits of good reproducibility, acceptable stability, wide
      linear range, low detection limit and simplicity, the proposed luminol ECL sensor
      showed great potential in the field of analytical applications.

PMID- 25618691
TI  - Rapid prototyping of pneumatically actuated hydrocarbon gel valves for
      centrifugal microfluidic devices.
AB  - A novel, easy to prototype hydrocarbon gel-based active valve was developed for
      use in centrifugal microfluidic devices. The valve has been demonstrated to
      restrict flow by an additional 1000 revolutions per minute (RPM) when compared to
      a passive capillary valve of the same size located at the same radius. Opening of
      the valve is accomplished in a contactless manner using a stream of focused
      compressed air. The ease of fabrication, low cost and small dimensions of the gel
      valve offer the potential for integration of multiple valves of this type into
      multi-process centrifugal microfluidic systems. 

PMID- 25618693
TI  - The use of solid-phase fluorescence spectroscopy in the characterisation of
      organic matter transformations.
AB  - Given its high sensitivity and non-destructive nature, fluorescence excitation
      emission matrix (EEM) spectroscopy is widely used to differentiate changes and
      transformations of dissolved or water-extracted organic matter (OM) in natural
      environments. The same technique applied directly on solid samples (solid-phase
      fluorescence spectroscopy, SPF-EEM) provides accurate results when used with
      pharmaceutical products or food samples, but only a few studies have considered
      natural OM. This study reports on the use of SPF-EEM on solid compost samples and
      emphasises the way the different maturation phases can be distinguished with
      fluorophores closely resembling those found in dissolved samples. A very good
      correlation has been found with data from Rock-Eval pyrolysis, nuclear magnetic
      resonance ((13)C CPMAS NMR), and humic-fulvic acid ratios determined by
      conventional NaOH-extraction. SPF-EEM appears as a much simpler method than the
      conventional ones to detect transformations in natural OM samples with low
      mineral contents. However, direct application to soil samples requires some
      additional studies. 

PMID- 25618694
TI  - Comprehensive two-dimensional gas chromatography and three-dimensional
      fluorometry for detection of volatile and bioactive substances in some berries.
AB  - The volatile fractions of Cape gooseberry and blueberry were determined by
      headspace solid-phase microextraction coupled with comprehensive two-dimensional
      gas chromatography with time-of-flight mass spectrometry (HS-SPME/GC*GC-TOFMS).
      The highest amount of alcohol (51.8%), ester (32.8%) and carboxylic acid (6.9%)
      was in blueberry in comparison with gooseberry and oppositely ketones (14.7%),
      aldehydes (9.9%) and terpenes (8%) were found in gooseberry. The bioactive
      compounds and antioxidant capacities were higher in blueberries than in
      gooseberries. Three dimensional fluorescence emission spectrometry (3D-FL) was
      applied to determine and to compare experimentally found binding parameters of
      berries extracts with human serum albumin (HSA). The fluorescence quenching of
      HSA by polyphenols from berries was a result of the formation of a polyphenol-HSA
      complex. The binding abilities of berries were highly correlated with the
      bioactivity of polyphenols and volatile substances. The cluster analysis (CA) and
      linear discriminant analysis (LDA) was applied to differentiate the berries
      samples according to their type. 

PMID- 25618695
TI  - Novel approach for labeling of biopolymers with DOTA complexes using in situ
      click chemistry for quantification.
AB  - In this work, we present a two-step labeling approach for the efficient tagging
      with lanthanide-containing complexes. For this purpose, derivatization of the
      cysteine residues with an alkyne group acting as linker was done before the DOTA
      complex was introduced using in situ click chemistry. The characterization of
      this new methodology is presented including the optimization of the labeling
      process, demonstration of the quantitative capabilities using both electrospray
      ionization mass spectrometry (ESI-MS) and inductively coupled plasma mass
      spectrometry (ICP-MS) detection, and study of the fragmentation behavior of the
      labeled peptides by collision-induced dissociation (CID) for identification
      purposes. The results show that, in terms of labeling efficiency, this new
      methodology improves previously developed DOTA-based label strategies, such as
      MeCAT-maleimide (metal-coded affinity tag, MeCAT-Mal) and MeCAT-iodoacetamide
      (MeCAT-IA) reagents. The goal of reducing the steric hindrance caused by the
      voluminous DOTA complex was fulfilled allowing both, quantification and
      identification of labeled biopolymers. 

PMID- 25618696
TI  - A novel ligandless-dispersive liquid-liquid microextraction method for matrix
      elimination and the preconcentration of rare earth elements from natural waters.
AB  - A new, simple, efficient and rapid separation method based on ligandless
      dispersive liquid-liquid microextraction (LL-DLLME) was developed for the
      preconcentration of rare earth elements (REEs) (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb,
      Dy, Ho, Er, Tm, Yb, Lu) in natural water samples, followed by inductively coupled
      plasma mass spectrometry (ICP-MS) detection. Carbon tetrachloride and acetone
      were used as extraction solvent and disperser solvent, respectively. The
      experimental parameters affecting the extraction efficiency such as sample pH,
      volume of extraction/disperser solvent and concentration of NaCl were
      investigated and optimized. Under the optimum conditions, detection limits
      between 0.68 and 26.6 ng L(-1) for a 5 mL sample volume were determined. The
      developed method was successfully applied to samples such as tap water, river
      water and seawater. Satisfactory recoveries were obtained with the percentage
      recovery values of the REEs for spiked water samples being between 94 and 111 for
      tap water, between 89 and 118 for river water and between 92 and 124 for
      seawater.

PMID- 25618697
TI  - Rhodium nanoparticle-modified screen-printed graphite electrodes for the
      determination of hydrogen peroxide in tea extracts in the presence of oxygen.
AB  - In this work we describe the fabrication of nanostructured electrocatalytic
      surfaces based on polyethyleneimine (PEI)-supported rhodium nanoparticles (Rh-NP)
      over graphite screen-printed electrodes (SPEs) for the determination of hydrogen
      peroxide in the presence of oxygen. Rh-NP, electrostatically stabilized by
      citrate anions, were immobilized over graphite SPEs, through coulombic attraction
      on a thin film of positively charged PEI. The functionalized sensors, polarized
      at 0.0 V vs. Ag/AgCl/3 M KCl, exhibited a linear response to H2O2 over the
      concentration range from 5 to 600 MUmol L(-1) H2O2 in the presence of oxygen. The
      3sigma limit of detection was 2 MUmol L(-1) H2O2, while the reproducibility of
      the method at the concentration level of 10 MUmol L(-1) H2O2 (n=10) and between
      different sensors (n=4) was lower than 3 and 5%, respectively. Most importantly,
      the sensors showed an excellent working and storage stability at ambient
      conditions and they were successfully applied to the determination of H2O2
      produced by autooxidation of polylphenols in tea extracts with ageing. Recovery
      rates ranged between 97 and 104% suggesting that the as-prepared electrodes can
      be used for the development of small-scale, low-cost chemical sensors for use in
      on-site applications.

PMID- 25618698
TI  - Amperometric uric acid biosensor based on poly(vinylferrocene)-gelatin
      carboxylated multiwalled carbon nanotube modified glassy carbon electrode.
AB  - In this study, a new uric acid biosensor was constructed based on ferrocene
      containing polymer poly(vinylferrocene) (PVF), carboxylated multiwalled carbon
      nanotubes (c-MWCNT) and gelatin (GEL) modified glassy carbon electrode (GCE).
      Uricase enzyme (UOx) was immobilized covalently through N-ethyl-N'-(3
      dimethyaminopropyl) carbodiimide (EDC) and N-hydroxyl succinimide (NHS) chemistry
      onto c-MWCNT/GEL/PVF/GCE. The c-MWCNT/GEL/PVF composite was characterized by
      scanning electron microscopy, cyclic voltammetry and electrochemical impedance
      spectroscopy. Various experimental parameters such as pH, applied potential,
      enzyme loading, PVF and c-MWCNT concentration were investigated in detail. Under
      the optimal conditions the dynamic linear range of uric acid was 2.0*10(-7) M
      7.1*10(-4) M (R=0.9993) with the detection limit low to 2.3*10(-8) M. With good
      selectivity and sensitivity, the biosensor was successfully applied to determine
      the uric acid in human serum. The results of the biosensor were in good agreement
      with those obtained from standard method. Therefore, the presented biosensor
      could be a good promise for practical applications in real samples.

PMID- 25618699
TI  - Ultrasensitive photoelectrochemical immunoassay through tag induced exciton
      trapping.
AB  - The development of photoelectrochemical (PEC) sensors with novel principles is of
      significance in realizing sensitive and low-cost detection. This work uses CuO
      NPs labeled antibody to construct a simple and sensitive sandwich-type
      immunobiosensor for the detection of protein. The detection signal is produced by
      dissolving the CuO NPs to release copper ions, which are then added on a quantum
      dots (QDs) modified F-doped tin oxide to quench the photocurrent of QDs via
      copper ion-induced formation of exciton trapping. The formed exciton trapping
      blocks the escape of photoelectron and thus leads to a "signal off" PEC method
      for sensitive immunoassay. The proposed method shows a detectable range from 0.05
      to 500 ng/mL for alpha-fetoprotein (AFP) with a detection limit (LOD) of 0.038
      ng/mL. This work further extends the application of exciton trapping-based PEC
      biosensing strategy in bioanalysis. The sensitive analytical performance of the
      designed route implies a promising potential of the PEC sensing in clinical
      diagnosis.

PMID- 25618700
TI  - Doxorubicin-tethered fluorescent silica nanoparticles for pH-responsive
      anticancer drug delivery.
AB  - The therapeutic potential of doxorubicin hydrochloride (DOX), an anticancer drug,
      is limited by its dose-related side effects and non-selective delivery to healthy
      and cancerous cells. Here we show a drug delivery system based on doxorubicin
      tethered fluorescent silica nanoparticles (DOX-Hyd@FSiNPs). The DOX was
      conjugated to the FSiNPs through a hydrazone linkage. After uptake into the
      acidic environment of cancer cells, DOX was released from the FSiNPs' surfaces
      because of the breakage of the pH-sensitive hydrazine bond. The decreased
      viability of cells in the HeLa cancer cell line indicates that DOX-Hyd@FSiNPs are
      potential candidates for cancer therapy. Nuclear staining and Z-axis scanning
      with confocal laser scanning microscopy demonstrated that DOX-Hyd@FSiNPs were
      effectively delivered into the cytoplasm of HeLa cells; the released DOX
      accumulating in the nucleus. The fluorescence of the FSiNPs also allowed the live
      tracking of the nanoparticles in the cell. 

PMID- 25618701
TI  - A new one-step antigen heterologous homogeneous fluorescence immunoassay for
      progesterone detection in serum.
AB  - A new homogeneous immunoassay for the detection of progesterone was developed to
      measure its concentration in human serum. We utilized the weak cross-reactivity
      of a monoclonal anti-progesterone antibody to an analog molecule (in this case
      beta-estradiol) to create a mixture, in which the fluorescence-labeled antibody
      (AbF) and quencher-labeled BSA-estradiol (eBSAq) were at optimized equilibrium.
      At this stage, most antibodies were bound to eBSAq and the fluorescence of AbF
      was quenched. After adding samples containing free progesterone to the system,
      these would replace the eBSAq at the antigen-binding site. The fluorescence would
      be released. In contrast to conventional competitive immunoassays, the
      fluorescence signal increases with increasing progesterone concentration, greatly
      simplifying detection and calibration. The performance of the assay was very
      simple; there was only one mixing step; and other hormones like testosterone,
      estradiol or dehydroepiandrosterone (DHEA) do not interfere the assay. A wide
      linear range from 0.1 ug/L to 100 ug/L was achieved in buffer, with a LOD of 0.1
      ug/L. In human serum the LOD was 5 ug/L, and the linear range was 5-500 ug/L. For
      this assay it is important to find the right combination of antibody and cross
      reactive antigen. If such a combination could be defined, it is conceivable to
      apply this assay to a wide range of analytes.

PMID- 25618702
TI  - Fourier transform spectral imaging microscopy (FT-SIM) and scanning Raman
      microscopy for the detection of indoor common contaminants on the surface of
      dental implants.
AB  - Endosteal dental implants are used routinely with high success rates to
      rehabilitate the integrity of the dentition. However if implant surfaces become
      contaminated by foreign material, osseointegration may not occur and the dental
      implant will fail because of the lack of mechanical stability. Detection and
      characterization of dental implant surface contaminants is a difficult task. In
      this article we investigate the application of several spectral microscopy
      methods to detect airborne contaminants on dental implant surfaces. We found that
      Fourier Transform Spectral Imaging Microscopy (FT-SIM) and scanning Raman
      microscopy provided the most useful information. Some implants possess weak and
      homogeneous auto-fluorescence and are best analyzed using FT-SIM methods, while
      others are Raman inactive and can be analyzed using scanning Raman microscopy. 

PMID- 25618703
TI  - Determination of tiopronin based on the enhancement of Ru(bpy)52+ co-reactant
      electrochemiluminescence.
AB  - It was found that tiopronin could strongly enhance the electrochemiluminescence
      of tris(2,2'-bipyridine) ruthenium(II) (Ru(bpy)3(2+)) in alkaline solution on a
      bare Pt electrode, based on which a sensitive, simple and rapid method for the
      determination of tiopronin was established. Under the optimal conditions, the
      logarithm of ECL enhancement has a linear relationship with the logarithm of
      tiopronin concentration in the range from 2.0*10(-7) to 2.0*10(-4) mol L(-1) with
      a detection limit of 1.0*10(-8) mol L(-1) (S/N= 3), and the relative standard
      deviation of 1.6% (n=7, c=5.0*10(-6) mol L(-1)). The proposed method has been
      applied to the determination of tiopronin in pharmaceutical preparations and the
      results were satisfactory with recoveries of 91.7+/-1.7%, 98.3+/-1.0% and 100.8+/
      0.5%, respectively, for three different concentration levels (0.61 MUmol L(-1),
      6.1 MUmol L(-1) and 12.2 MUmol L(-1)). According to the study of electrochemical
      behavior, ECL behavior and ECL emission spectrum of Ru(bpy)3(2+)/tiopronin
      system, a possible ECL mechanism was proposed.

PMID- 25618704
TI  - Evaluation and modelling of dissolved organic matter reactivity toward As(III)
      and As(V) - implication in environmental arsenic speciation.
AB  - Many studies have been carried out to identify dissolved organic matter-trace
      metals interactions, as organic matter (OM) was demonstrated to be a governing
      parameter of metals speciation. Concerning arsenic (As), such OM-As studies are
      scarce and concluded that, when As binding occurred, it was probably through
      cationic bridges or, in some cases, directly. Yet, analytical proofs remained
      complex to obtain. In this work, As binding with Suwanee River Humic Acid (SRHA),
      as an example of dissolved organic matter, was studied, considering both As(III)
      and As(V), at various pH and in absence/presence of Na and Ca. Dialysis,
      fluorescence measurements and PHREEQC modelling were performed to identify and
      characterize the mechanisms at work for the various performed experiments. It was
      observed that As(III) binding on SRHA occurred through direct SRHA-As(III)
      binding and that neither Na nor Ca presence modify this mechanism. As(V) appeared
      to be also bound by SRHA through direct interaction, but suffered from the
      competition of Na for the SRHA binding sites. Oppositely, in presence of Ca, the
      overall As(V)-SRHA binding was significantly enhanced, Ca acting as an efficient
      cationic bridge through the formation of an SRHA-Ca-As(V) ternary complex. All
      the obtained data were satisfactorily simulated using a unique set of binding
      parameters which can therefore be implemented in any speciation code to better
      address As behaviour in environmental conditions. 

PMID- 25618705
TI  - Effect of template ion-ligand complex stoichiometry on selectivity of ion
      imprinted polymers.
AB  - In order to highlight the importance of the complex stoichiometry during ion
      imprinted polymer (IIP) synthesis, we investigated the effect of the complex
      structure on IIPs selectivity by adjusting the complex stoichiometry before
      polymerization. 2-(aminomethyl)pyridine monomer (amp) was chosen as a
      functionalized ligand for nickel(II) ions and a polymerizable vinylbenzyl
      derivative (Vbamp) was prepared. Complex formation was studied by varying the
      nickel/Vbamp ratio and recording absorption spectra of the complexes at the
      polymerization conditions. Using a least-squares minimization scheme, the complex
      species distribution was successfully established. From these results, it was
      possible to choose the metal/ligand stoichiometry in the complex (1:1; 1:2 or
      1:3) by adjusting the initial metal/ligand ratio. IIPs were then prepared by
      inverse suspension copolymerization of Vbamp with ethyleneglycol dimethacrylate
      (EDMA). Highly porous particles with good nickel binding capacity and good Ni/Zn
      selectivity even at acidic conditions were obtained. Equilibrium uptake of Ni(II)
      at pH 7 ranged from 0.12 to 0.2 mmol g(-1) and relative selective coefficient was
      as high as 260 for the IIP prepared using the Ni(Vbamp)2 complex.

PMID- 25618706
TI  - Surface morphology changes of polymer membrane and carbon paste sertraline
      sensors.
AB  - Polymer membrane and chemically modified carbon paste (CMCP) sensors for
      determination of sertraline HCl (Ser-Cl) incorporating sertraline
      tetraphenylborate (Ser-TPB) as an electro-active material were constructed. They
      showed a rapid and linear response for Ser-ion over the concentration range 0.01
      10.00 mmol L(-1). The limits of detection were 2.80 and 9.55 MUmol L(-1), and
      Nernastian slopes were 56.60, 59.60 mV decade(-1) for membrane and CMCP sensors
      for batch method. In flow injection analysis (FIA), the electrodes revealed
      comparatively good selectivity for Ser-ion with regard to a wide variety of
      different cations, sugars, and amino acids. The addition of different anionic
      additives, namely sodium tetraphenylborate (NaTPB), potassium tetraphenylborate
      (KTPB), potassium tetrakis[3,5-bis-(triflouromethyl)phenyl]borate (KTFMPB), and
      sodium tetrakis[3,5-bis(trifluoro-methyl)phenyl]borate (NaTFMPB), to the prepared
      mixture improved their response characteristics. The surface morphologies of
      membrane films containing PVC only (blank), plasticizer+PVC, Ser
      TPB+plasticizer+PVC, and Ser-TPB +plasticizer+PVC+additive were studied using
      scanning and atomic force electron microscopes. These sensors had been used in
      the potentiometric titration of Ser-ion against NaTPB. Standard addition method
      for the pure raw material and some of its pharmaceutical tablets was used for Ser
      Cl determination. The obtained results were tested for their repeatability and
      reproducibility and were statistically treated by F- and t- tests.

PMID- 25618707
TI  - Fullerene-C60-MWCNT composite film based ultrasensitive electrochemical sensing
      platform for the trace analysis of pyruvic acid in biological fluids.
AB  - We propose development of a novel electrochemical sensor based on fullerene-multi
      walled carbon nanotubes composite film for the sensitive determination of the
      pyruvic acid in biological fluids. The developed sensor was characterized by
      cyclic voltammetry. The nanocomposite film of C60-MWCNTs on GCE exhibits
      electrocatalytic activity towards pyruvic acid reduction and also decreases the
      reduction overpotential. The influence of the optimization parameters such as pH
      and effect of loading of composite mixture of C60 and MWCNTs on the
      electrochemical performance of the sensor were evaluated. Various kinetic
      parameters such as electron transfer number (n=2), proton transfer number (m=2)
      and charge transfer coefficient (alpha=0.56) were also calculated. Under
      optimized conditions, the squarewave reduction peak current was linear over the
      concentration range of 2.0-55 nM with the detection and quantification limit of
      0.1 nM and 0.8 nM respectively. The fabricated sensor was successfully applied to
      the detection of pyruvic acid in biological samples with good recovery ranging
      from 97.6% to 103.6%.

PMID- 25618708
TI  - Determination of phenolic compounds in air by using cyclodextrin-silica hybrid
      microporous composite samplers.
AB  - An analytical method for the determination of phenolic compounds in air samples
      based on the use of cyclodextrin-silica hybrid microporous composite samplers is
      proposed. The method allows the determination of phenol, guaiacol, cresol
      isomers, eugenol, 4-ethylphenol and 4-ethylguaiacol in workplaces according to
      the Norm UNE-EN 1076:2009 for active sampling. Therefore, the proposed method
      offers an alternative for the assessment of the occupational exposure to phenol
      and cresol isomers. The detection limits of the proposed method are lower than
      those for the NIOSH Method 2546. Storage time of samples almost reaches 44 days.
      Recovery values for phenol, guaiacol, o-cresol, m-cresol, p-cresol, 4
      ethylguaiacol, eugenol and 4-ethylphenol are 109%, 99%, 102%, 94%, 94%, 91%, 95%
      and 102%, respectively with a coefficient of variation below 6%. The method has
      been applied to the assessment of exposure in different areas of a farm and
      regarding the quantification of these compounds in the vapors generated by
      burning incense sticks and an essential oil marketed as air fresheners. The
      acquired results are comparable with those provided from a reference method for a
      95% of confidence level. The possible use of these samplers for the sampling of
      other toxic compounds such as phthalates is evaluated by qualitative analysis of
      extracts from incense sticks and essential oil samples. 

PMID- 25618709
TI  - Plasmonic detection of Cd2+ ions using surface-enhanced Raman scattering active
      core-shell nanocomposite.
AB  - The present study was structured to address development of an efficient devise
      for sensing of toxic Cd(2+) ions at trace level in aqueous media. In order to
      achieve this objective, the speckled core-shell nanocomposites (NCs) of silica
      gold (SiO2@Au) using ~30 nm diameter of spherical gold nanoparticles (Au NPs)
      with 420 nm diameter of silica cores was synthesized. Au NPs showed the surface
      plasmon resonance (SPR) peak at 522 nm and spherical core-shell particles at 541
      nm. Both Au NPs and SiO2@Au solutions were found to be sensitive to Cd(2+) ions
      in aqueous sample. The colour change occurred in presence of SiO2@Au at 0.1 ppm
      (100 ppb) of Cd(2+) ions whereas 2 ppm (2000 ppb) concentration of Cd(2+) ions
      was necessary for the colour change in Au NPs solution confirmed that SERS active
      SiO2@Au core-shell NCs 20 times more sensitive compared to Au NPs. The technique
      using SiO2@Au NCs is quantitative between 100 and 2000 ppb (0.1 to 2 ppm) while
      effective but non-quantitative above upto 10 ppm, the maximum concentration
      studied in present investigation. The detection limit using SiO2@Au NCs is 100
      ppb (0.1 ppm) while Au NPs is able to detect Cd(2+) as low as 2000 ppb (2 ppm).
      The scanning electron microscopy (SEM) of Au NPs and SiO2@Au particles showed
      aggregation of Au NPs and SiO2@Au NCs in the presence of Cd(2+) ions. The surface
      enhanced Raman spectroscopy (SERS) was used to compare sensitivities of Au NPs
      and SiO2@Au towards Cd(2+) ions and confirmed that SiO2@Au core-shell NCs is 20
      times more sensitive than Au NPs.

PMID- 25618710
TI  - Experimental design for TBT quantification by isotope dilution SPE-GC-ICP-MS
      under the European water framework directive.
AB  - In Europe the maximum allowable concentration for tributyltin (TBT) compounds in
      surface water has been regulated by the water framework directive (WFD) and
      daughter directive that impose a limit of 0.2 ng L(-1) in whole water (as
      tributyltin cation). Despite the large number of different methodologies for the
      quantification of organotin species developed in the last two decades,
      standardised analytical methods at required concentration level do not exist. TBT
      quantification at picogram level requires efficient and accurate sample
      preparation and preconcentration, and maximum care to avoid blank contamination.
      To meet the WFD requirement, a method for the quantification of TBT in mineral
      water at environmental quality standard (EQS) level, based on solid phase
      extraction (SPE), was developed and optimised. The quantification was done using
      species-specific isotope dilution (SSID) followed by gas chromatography (GC)
      coupled to inductively coupled plasma mass spectrometry (ICP-MS). The analytical
      process was optimised using a design of experiment (DOE) based on a factorial
      fractionary plan. The DOE allowed to evaluate 3 qualitative factors (type of
      stationary phase and eluent, phase mass and eluent volume, pH and analyte
      ethylation procedure) for a total of 13 levels studied, and a sample volume in
      the range of 250-1000 mL. Four different models fitting the results were defined
      and evaluated with statistic tools: one of them was selected and optimised to
      find the best procedural conditions. C18 phase was found to be the best
      stationary phase for SPE experiments. The 4 solvents tested with C18, the pH and
      ethylation conditions, the mass of the phases, the volume of the eluents and the
      sample volume can all be optimal, but depending on their respective combination.
      For that reason, the equation of the model conceived in this work is a useful
      decisional tool for the planning of experiments, because it can be applied to
      predict the TBT mass fraction recovery when the experimental conditions are
      drawn. This work shows that SPE is a convenient technique for TBT pre
      concentration at pico-trace levels and a robust approach: in fact (i) number of
      different experimental conditions led to satisfactory results and (ii) the
      participation of two institutes to the experimental work did not impact the
      developed model.

PMID- 25618711
TI  - A systematic study on the influencing parameters and improvement of quantitative
      analysis of multi-component with single marker method using notoginseng as
      research subject.
AB  - A new quantitative analysis of multi-component with single marker (QAMS) method
      for 11 saponins (ginsenosides Rg1, Rb1, Rg2, Rh1, Rf, Re and Rd; notoginsenosides
      R1, R4, Fa and K) in notoginseng was established, when 6 of these saponins were
      individually used as internal referring substances to investigate the influences
      of chemical structure, concentrations of quantitative components, and purities of
      the standard substances on the accuracy of the QAMS method. The results showed
      that the concentration of the analyte in sample solution was the major
      influencing parameter, whereas the other parameters had minimal influence on the
      accuracy of the QAMS method. A new method for calculating the relative correction
      factors by linear regression was established (linear regression method), which
      demonstrated to decrease standard method differences of the QAMS method from
      1.20%+/-0.02% - 23.29%+/-3.23% to 0.10%+/-0.09% - 8.84%+/-2.85% in comparison
      with the previous method. And the differences between external standard method
      and the QAMS method using relative correction factors calculated by linear
      regression method were below 5% in the quantitative determination of Rg1, Re, R1,
      Rd and Fa in 24 notoginseng samples and Rb1 in 21 notoginseng samples. And the
      differences were mostly below 10% in the quantitative determination of Rf, Rg2,
      R4 and N-K (the differences of these 4 constituents bigger because their contents
      lower) in all the 24 notoginseng samples. The results indicated that the contents
      assayed by the new QAMS method could be considered as accurate as those assayed
      by external standard method. In addition, a method for determining applicable
      concentration ranges of the quantitative components assayed by QAMS method was
      established for the first time, which could ensure its high accuracy and could be
      applied to QAMS methods of other TCMs. The present study demonstrated the
      practicability of the application of the QAMS method for the quantitative
      analysis of multi-component and the quality control of TCMs and TCM
      prescriptions. 

PMID- 25618712
TI  - A rapid, one step preparation for measuring selected free plus SO2-bound wine
      carbonyls by HPLC-DAD/MS.
AB  - Carbonyl compounds are produced during fermentation and chemical oxidation during
      wine making and aging, and they are important to wine flavor and color stability.
      Since wine also contains these compounds as alpha-hydroxysulfonates as a result
      of their reaction with sulfur dioxide, an alkaline pre-treatment requiring oxygen
      exclusion has been used to release these bound carbonyls for analysis. By
      modifying the method to hydrolyze the hydroxysulfonates with heating and acid in
      the presence of 2,4-dinitrophenylhydrazine (DNPH), the carbonyl compounds are
      simultaneously and quickly released and derivatized, resulting in a simpler and
      more rapid method. In addition, the method avoids air exclusion complications
      during hydrolysis by the addition of sulfur dioxide. The method was optimized for
      temperature, reaction time, and the concentrations of DNPH, sulfur dioxide and
      acid. The hydrazones were shown to be stable for 10 h, adequate time for
      chromatographic analysis by HPLC-DAD/MS. This method is demonstrated for 2
      ketoglutaric acid, pyruvic acid, acetoin and acetaldehyde, wine carbonyls of very
      different reactivities, and it offers good specificity, high recovery and low
      limits of detection. This new rapid, simple method is demonstrated for the
      measurement of carbonyl compounds in a range of wines of different ages and grape
      varieties.

PMID- 25618713
TI  - A non-aggregation spectrometric determination for mercury ions based on gold
      nanoparticles and thiocyanuric acid.
AB  - We provide a highly sensitive and selective colorimetric assay to detect mercury
      ions (Hg(2+)) in aqueous environment using thiocyanuric acid (TCA) molecule
      functionalized gold nanoparticles (AuNPs). This method is based on the
      thiophilicity of Hg(2+) and AuNPs as well as the unique optical properties of TCA
      functionalized AuNPs. In the presence of TCA, AuNPs aggregate due to the strong
      attraction between thiol groups of TCA and surface-bounded AuCl4(-)/AuCl2(-)
      ions, which induces the visible color change from red to blue. With the addition
      of Hg(2+), Hg(2+) is more apt to interact with thiols than AuNPs. Thus, Hg(2+)
      can remove the AuNPs of the TCA-functionalized AuNPs and trigger AuNP aggregation
      redisperse again. This assay can selectively detect Hg(2+) with the detection
      limits as low as 0.5 nM in aqueous solution.

PMID- 25618714
TI  - Generation of non-multilinear three-way voltammetric arrays by an
      electrochemically oxidized glassy carbon electrode as an efficient electronic
      device to achieving second-order advantage: challenges, and tailored
      applications.
AB  - For the first time, several second-order calibration models based on artificial
      neural network-residual bilinearization (ANN-RBL), unfolded-partial least squares
      RBL (U-PLS/RBL), multidimensional-partial least squares-RBL (N-PLS/RBL),
      multivariate curve resolution-alternating least squares (MCR-ALS), and parallel
      factor analysis 2 (PARAFAC2) were used to exploiting second-order advantage to
      identify which technique offers the best predictions for the simultaneous
      quantification of norepinephrine (NE), paracetamol (AC), and uric acid (UA) in
      the presence of pteroylglutamic acid (FA) as an uncalibrated interference at an
      electrochemically oxidized glassy carbon electrode (OGCE). Three-way differential
      pulse voltammetric (DPV) arrays were obtained by recording the DPV signals at
      different pulse heights. The recorded three-way arrays were both non-bilinear and
      non-trilinear therefore, the observed shifts in the recorded DPV data were
      corrected using correlation optimised warping (COW) algorithm. All the algorithms
      achieved the second-order advantage and were in principle able to overcome the
      problem of the presence of unexpected interference. Comparison of the performance
      of the applied second-order chemometric algorithms confirmed the more superiority
      of U-PLS/RBL to resolve complex systems. The results of applying U-PLS/RBL for
      the simultaneous quantification of the studied analytes in human serum samples
      were also encouraging. 

PMID- 25618715
TI  - Ionic liquids for improving the extraction of NSAIDs in water samples using
      dispersive liquid-liquid microextraction by high performance liquid
      chromatography-diode array-fluorescence detection.
AB  - A rapid, sensitive and efficient analytical method based on the use of ionic
      liquids for determination of non-steroidal anti-inflammatory drugs (NSAIDs) in
      water samples was developed. High-performance liquid chromatography equipped with
      a diode array and fluorescence detector was used for quantification of
      ketoprofen, ibuprofen and diclofenac in tap and river water samples. This new
      method relies on the use of two ionic liquids with multiple functionalities: one
      functions as an extraction solvent (1-butyl-3-methylimidazolium
      hexafluorophosphate ([BMIM][PF6]), and the other changes the polarity in the
      aqueous medium (1-butyl-3-methylimidazolium tetrafluoroborate, ([BMIM][BF4]).
      Factors such as the type and volume of the ILs and dispersive solvent, sample
      volume, and centrifugation time were investigated and optimized. The optimized
      method exhibited good precision, with relative standard deviation values between
      2% and 3%, for the three NSAIDs. Limits of detection achieved for all of the
      analytes were between 17 and 95 ng mL(-1), and the recoveries ranged from 89% to
      103%. Furthermore, the enrichment factors ranged from 49 to 57. The proposed
      method was successfully applied to the analysis of NSAIDs in tap and river water
      samples.

PMID- 25618716
TI  - Unveiling the identity of distant targets through advanced Raman-laser-induced
      breakdown spectroscopy data fusion strategies.
AB  - Data fusion is the process of combining data gathered from two or more sensors to
      produce a more specific, comprehensive and unified dataset of the inspected
      target. On this basis, much has been said about the possible benefits resulting
      from the use of molecular and atomic information for the detection of explosives.
      The orthogonal nature of the spectral and compositional information provided by
      Raman spectroscopy and laser-induced breakdown spectroscopy (LIBS) makes them
      suitable candidates for an optimal combination of their data, thus achieving
      inferences that are not feasible using a single sensor. The present manuscript
      evaluates several architectures for the combination of spectral outputs from
      these two sensors in order to compare the benefits and drawbacks of data fusion
      for improving the overall identification performance. From the simple assembling
      (concatenation or addition) of Raman and LIBS spectra to signals' processing on
      the basis of linear algebra (either the outer product or the outer sum),
      different identification patterns of several compounds (explosives, potential
      confusants and supports) have been built. The efficiency on target
      differentiation by using each of the architectures has been evaluated by
      comparing the identification yield obtained for all the inspected targets from
      correlation and similarity measurements. Additionally, a specific code integrated
      by several of these patterns to identify each compound has also been evaluated.
      This approach permits to obtain a better knowledge about the identity of an
      interrogated target, mainly in those decisive cases in which LIBS or Raman cannot
      be effective separately to reach a decision. 

PMID- 25618717
TI  - Trace level voltammetric determination of lead and cadmium in sediment pore water
      by a bismuth-oxychloride particle-multiwalled carbon nanotube composite modified
      glassy carbon electrode.
AB  - Two multiwalled carbon nanotubes-based composites modified with bismuth and
      bismuth-oxychloride particles were synthesized and attached to the glassy carbon
      electrode substrate. The resultant configurations, Bi/MWCNT-GCE and BiOCl/MWNT
      GCE, were then characterized with respect to their physicochemical properties and
      electroanalytical performance in combination with square-wave anodic stripping
      voltammetry (SWASV). Further, some key experimental conditions and instrumental
      parameters were optimized; namely: the supporting electrolyte composition,
      accumulation potential and time, together with the parameters of the SWV-ramp.
      The respective method with both electrode configurations has then been examined
      for the trace level determination of Pb(2+) and Cd(2+) ions and the results
      compared to those obtained with classical bismuth-film modified GCE. The
      different intensities of analytical signals obtained at the three electrodes for
      Pb(2+) and Cd(2+) vs. the saturated calomel reference electrode had indicated
      that the nature of the modifiers and the choice of the supporting electrolyte
      influenced significantly the corresponding stripping signals. The most promising
      procedure involved the BiOCl/MWCNT-GCE and the acetate buffer (pH 4.0) offering
      limits of determination of 4.0 MUg L(-1) Cd(2+) and 1.9 MUg L(-1) Pb(2+) when
      accumulating for 120 s at a potential of -1.20 V vs. ref. The BiOCl/MWCNT
      electrode was tested for the determination of target ions in the pore water of a
      selected sediment sample and the results agreed well with those obtained by
      graphite furnace atomic absorption spectrometry.

PMID- 25618719
TI  - Determination of benzophenone-UV filters in human milk samples using ultrasound
      assisted extraction and clean-up with dispersive sorbents followed by UHPLC-MS/MS
      analysis.
AB  - A new sample preparation method for the determination of five benzophenone UV
      filters in human breast milk has been developed. The procedure involves the
      lyophilization of the sample, and its subsequent extraction by ultrasound
      sonication using acetonitrile. In order to reduce matrix effects produced by milk
      components that are coextracted, mainly proteins, sugars and lipids, a further
      clean-up step with a mixture of dispersive-SPE sorbents, C18 and PSA, was
      applied. Extraction parameters were optimized using experimental design, and the
      compounds were detected and quantified by ultrahigh performance liquid
      chromatography tandem mass spectrometry (UHPLC-MS/MS) in positive ESI mode.
      Analytes were separated in 10 min. BP-d10 was used as internal standard. The
      limits of detection (LODs) were between 0.1 and 0.2 ng mL(-1), and the limits of
      quantification (LOQs) were between 0.3 and 0.6 ng mL(-1) for the target analytes.
      The inter- and intra-day variability was <12%. The method was validated using
      matrix-matched calibration and recovery assays with spiked samples. Recovery
      rates were between 90.9 and 109.5%. The method was successfully applied for the
      determination of these compounds in human milk samples collected from volunteers
      lactating mothers with no known occupational exposure to these compounds who live
      in the province of Granada (Spain). The analytical method developed here may be
      useful for the development of more in-depth studies on the prenatal exposure and
      biomonitoring of these commonly used UV-filters.

PMID- 25618718
TI  - Magnetic molecularly imprinted polymer for the selective extraction of
      quercetagetin from Calendula officinalis extract.
AB  - A new magnetic molecularly imprinted polymers (MMIPs) for quercetagetin was
      prepared by surface molecular imprinting method using super paramagnetic core
      shell nanoparticle as the supporter. Acrylamide as the functional monomer,
      ethyleneglycol dimethacrylate as the crosslinker and acetonitrile as the porogen
      were applied in the preparation process. Fourier transform infrared spectrometer
      (FT-IR), X-ray diffraction (XRD) and Vibrating sample magnetometer (VSM) were
      applied to characterize the MMIPs, and High performance liquid chromatography
      (HPLC) was utilized to analyze the target analytes. The selectivity of
      quercetagetin MMIPs was evaluated according to their recognition to template and
      its analogues. Excellent binding for quercetagetin was observed in MMIPs
      adsorption experiment, and the adsorption isotherm models analysis showed that
      the homogeneous binding sites were distributed on the surface of the MMIPs. The
      MMIPs were employed as adsorbents in solid phase extraction for the determination
      of quercetagetin in Calendula officinalis extracts. Furthermore, this method is
      fast, simple and could fulfill the determination and extraction of quercetagetin
      from herbal extract. 

PMID- 25618720
TI  - Development of a method to screen and isolate potential xanthine oxidase
      inhibitors from Panax japlcus var via ultrafiltration liquid chromatography
      combined with counter-current chromatography.
AB  - Panax japlcus var is a typical Chinese herb with a large number of saponins
      existing in all parts of it. The common methods of screening and isolating
      saponins are mostly labor-intensive and time-consuming. In this study, a new
      assay based on ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS)
      was developed for the rapid screening and identifying of the ligands for xanthine
      oxidase from the extract of P. japlcus. Six saponins were identified as xanthine
      oxidase inhibitors from the extract. Subsequently, the specific binding ligands,
      namely, 24 (R)-majoroside R1, chikusetsusaponin IVa, oleanolic acid-28-O-beta-D
      glucopyranoside, notoginsenoside Fe, ginsenoside Rb2 and ginsenoside Rd (the
      purities of them were 95.74%, 96.12%, 93.19%, 94.83%, 95.07% and 94.62%,
      respectively) were separated by high-speed counter-current chromatography
      (HSCCC). The component ratio of the solvent system of HSCCC was calculated with
      the help of a multiexponential function model was optimized. The partition
      coefficient (K) values of the target compounds and resolutions of peaks were
      employed as the research indicators, and exponential function and binomial
      formulas were used to optimize the solvent system and flow rate of the mobile
      phases in a two-stage separation. An optimized two-phase solvent system composed
      of ethyl acetate, isopropanol, 0.1% aqueous formic acid (1.9:1.0:1.3, v/v/v, for
      the first-stage) and that composed of methylene chloride, acetonitrile,
      isopropanol, 0.1% aqueous formic acid (5.6:1.0:2.4:5.2, v/v/v/v, for the second
      stage) were used to isolate the six compounds from P. japlcus. The targeted
      compounds isolated, collected and purified by HSCCC were analyzed by high
      performance liquid chromatography (UPLC), and the chemical structures of all the
      six compounds were identified by UV, MS and NMR. The results demonstrate that UF
      LC-MS combined with HSCCC might provide not only a powerful tool for screening
      and isolating xanthine oxidase inhibitors in complex samples but also a useful
      platform for discovering bioactive compounds for the prevention and treatment of
      gout.

PMID- 25618721
TI  - Uranium monitoring tool for rapid analysis of environmental samples based on
      automated liquid-liquid microextraction.
AB  - A fully automated in-syringe (IS) magnetic stirring assisted (MSA) liquid-liquid
      microextraction (LLME) method for uranium(VI) determination was developed,
      exploiting a long path-length liquid waveguide capillary cell (LWCC) with
      spectrophotometric detection. On-line extraction of uranium was performed within
      a glass syringe containing a magnetic stirrer for homogenization of the sample
      and the successive reagents: cyanex-272 in dodecane as extractant, EDTA as
      interference eliminator, hydrochloric acid to make the back-extraction of U(VI)
      and arsenazo-III as chromogenic reagent to accomplish the spectrophotometric
      detection at 655 nm. Magnetic stirring assistance was performed by a specially
      designed driving device placed around the syringe body creating a rotating
      magnetic field in the syringe, and forcing the rotation of the stirring bar
      located inside the syringe. The detection limit (LOD) of the developed method is
      3.2 ug L(-1). Its good interday precision (Relative Standard Deviation, RSD
      3.3%), and its high extraction frequency (up to 6 h(-1)) makes of this method an
      inexpensive and fast screening tool for monitoring uranium(VI) in environmental
      samples. It was successfully applied to different environmental matrices: channel
      sediment certified reference material (BCR-320R), soil and phosphogypsum
      reference materials, and natural water samples, with recoveries close to 100%.

PMID- 25618722
TI  - Determination of five antiarrhythmic drugs in human plasma by dispersive liquid
      liquid microextraction and high-performance liquid chromatography.
AB  - A fast and sensitive high-performance liquid chromatography (HPLC) method with
      ultraviolet (UV) detection was developed and validated for the simultaneous
      quantitation of five antiarrhythmic drugs (metoprolol, propranolol, carvedilol,
      diltiazem, and verapamil) in human plasma samples. It involves dispersive liquid
      liquid microextraction (DLLME) of the desired drugs from 660 uL plasma and
      separation using isocratic elution with UV detection at 200 nm. The complete
      separation of all analytes was achieved within 7 min. Acetonitrile (as disperser
      solvent) resulting from the protein precipitation procedure was mixed with 100 uL
      dichloromethane (as an extraction solvent) and rapidly injected into 5 mL aqueous
      solution (pH 11.5) containing 1% (w/v), NaCl. After centrifugation, the
      sedimented phase containing enriched analytes was collected and evaporated to
      dryness. The residue was re-dissolved in 50 uL de-ionized water (acidified to pH
      3) and injected into the HPLC system for analysis. Under the optimal conditions,
      the enrichment factors and extraction recoveries ranged between 4.4-10.8 and 33
      82%, respectively. The suggested method was linear (r(2) >=0.997) over a dynamic
      range of 0.02-0.80 ug mL(-1) in plasma. The intra- and inter-days relative
      standard deviation (RSD%) and relative error (RE%) values of the method were
      below 20%, which shows good precision and accuracy. Finally, this method was
      applied to the analysis of real plasma samples obtained from the patients treated
      with these drugs.

PMID- 25618723
TI  - Influence of pre-treatment process on matrix effect for the determination of musk
      fragrances in fish and mussel.
AB  - Musk compounds are widely used as fragrances in personal care products. On
      account of their widespread use and their low biodegradation, they can be found
      in environmental samples. In our study two extraction methodologies were compared
      and different clean-up strategies were also studied in order to develop a
      reliable analytical method, with minimum matrix effect and good detection limits,
      to determine synthetic musk fragrances- six polycyclic musks, three nitro musks
      and the degradation product of one polycyclic musk- in fish and mussel samples.
      The first extraction technique involves a QuEChERS extraction, a consolidate
      extraction methodology in the field of food analysis of growing interest over
      recent years, followed by a dispersive solid-phase extraction (dSPE) as clean-up
      strategy. The second extraction technique consists of a conventional pressurised
      liquid extraction (PLE) with dichloromethane and an in-cell clean-up to decrease
      the matrix effect and remove the undesired components(*)present in PLE extracts.
      Large volume injection (LVI) followed by gas chromatography-ion trap-tandem mass
      spectrometry (GC-IT-MS/MS) was chosen as the separation and detection technique.
      Validation parameters, such as method detection limits and method quantification
      limits were found at ng g(-1) levels for both fish and mussel matrices. Good
      levels of intra-day and inter-day repeatabilities were obtained analysing fish
      and mussel samples spiked at 50 ng g(-1) (d.w.) (n=5, RSDs<17%). The developed
      PLE/GC-IT-MS/MS method was successfully applied to determine the target musk
      fragrances present in fish and mussel samples from the local market in Tarragona
      and fish samples from the Ebro River. The results showed the presence of
      galaxolide (2.97-18.04 ng g(-1) (d.w.)) and tonalide (1.17-8.42 ng g(-1) (d.w.))
      in all the samples analysed, while the remaining polycyclic musks such as
      cashmeran, celestolide and phantolide, were only detected in some of the fish
      samples analysed. None of the samples analysed contained detectable traces of the
      nitro musks studied.

PMID- 25618724
TI  - A new electrochemical aptasensor based on electrocatalytic property of graphene
      toward ascorbic acid oxidation.
AB  - Based on the superior electrocatalytic property of graphene (GN) toward ascorbic
      acid (AA) oxidation, a new electrochemical aptasensor has been developed. Here,
      adenosine triphosphate (ATP) is used as the model to demonstrate the performance
      of the developed aptasensor. Briefly, GN is attached to the thiolated ATP binding
      aptamer (ABA) modified gold electrode through pi-pi stacking interaction,
      resulting in a significant oxidation signal of AA. In the presence of ATP, the
      formation of ATP-ABA complex leads to the release of GN from sensing interface,
      resulting in a sharp decrease of the oxidation peak current of AA and an
      obviously positive shift of the related peak potential. Taking both the change
      values of the peak current and peak potential of AA oxidation as the response
      signals, ATP can be detected sensitively. This is the first time to demonstrate
      the application of GN as the nanocatalyst in an amplified aptasensor. It can be
      expected that GN, as nanocatalyst, should become the very promising amplifying
      elements in DNA-based electrochemical biosensors. 

PMID- 25618725
TI  - Label-free detection microarray for novel peptide ligands screening base on MS
      SPRi combination.
AB  - Peptides ligands with high affinity and high specificity towards specific targets
      is catching a good deal of interests in biomedical field. Traditional peptide
      screening procedure involves selection, sequencing and characterization and each
      step is time-consuming and labor-intensive. The combination between different
      analytical methods could provide an integrated plan for efficient peptide
      screening. We report herein a label-free detection microarray system to
      facilitate the whole one-bead-one-compound (OBOC) peptide screening process. A
      microwell array chip with two identical units can trap the candidate peptide
      beads in one-well-one-bead manner. Peptides on beads were photo-released in situ
      in the well and partly transferred to two identical chips for Surface Plasmon
      Resonance imaging (SPRi), and peptide left in the bi-unit microwell array chip
      was remain for in situ single bead sequencing by matrix-assisted laser desorption
      ionization time of flight mass spectrometry (MALDI-TOF-MS). Using the bi-unit
      imprinted chip system, affinity peptides towards AD protein were efficiently
      screened out both qualitatively and quantitatively from 10(4) candidates. The
      method provides a universal solution for high efficiency and high throughput
      ligands screening. 

PMID- 25618726
TI  - Colorimetric detection of hydrogen peroxide and glucose using the magnetic
      mesoporous silica nanoparticles.
AB  - In this work, we synthesized a type of magnetic mesoporous silica nanoparticle
      (denoted as Fe3O4@MSN) with Fe3O4 as the core and mesoporous silica the shell.
      The superparamagnetic Fe3O4-core provides high peroxidase-mimic activity and
      makes the artificial enzymatic system easily recyclable. Furthermore, Fe3O4
      nanoparticles are encapsulated in MSN shells to hinder the aggregation and keep
      them stable even under harsh conditions. Meanwhile, small active molecules are
      allowed to diffuse in and out of the MSN shells. Based on these functional units,
      the Fe3O4@MSN as robust nanoreactors can catalyze a self-organized cascade
      reaction, which includes oxidation of glucose by oxygen to yield gluconic acid
      and H2O2, and the latter further oxidizes 3,3,5,5-tetramethylbenzidine (TMB) to
      produce a color change. The Fe3O4@MSN, whose catalytic efficiency was not
      strongly dependent on pH and temperature, was successfully used for the detection
      of glucose and showed excellent sensitivity with a detection limit of 0.4*10(-5)
      mol/L. Nevertheless, the assay is also highly selective toward the glucose
      detection.

PMID- 25618727
TI  - Non-destructive detection of fish spoilage using a wireless basic volatile
      sensor.
AB  - A hydrogel-pH-electrode based near-field passive volatile sensor is described for
      real-time monitoring of fish spoilage. The sensor employs a varactor-based LC
      resonator that can be interrogated remotely using inductive coupling. The
      sensor's resonant frequency varies in response to the basic volatile spoilage
      compounds (total volatile basic nitrogen, TVB-N) in the headspace of packaged
      fish. The sensor is shown to have a linear response to logarithm of the ammonia
      gas concentration with a detection limit of 0.001 mg L(-1) (1.5 ppm). Trials on
      tilapia at 24  degrees C and 4  degrees C, employing direct comparison of sensor
      measurements with microbial analysis, indicate that the sensor response is
      correlated with the bacterial growth pattern in fish samples. It is shown that
      the sensor can distinctly identify when the product rejection level (10(7) cfu g(
      1) bacterial population) occurs for both 24  degrees C and 4  degrees C storage
      conditions. This demonstrates a potential for real-time monitoring of fish
      spoilage. The wireless sensor is suited to embedding in packaging material and
      does not require an integrated circuit, making it amenable to inexpensive mass
      production using printed electronic technology.

PMID- 25618728
TI  - Negative corona discharge-ion mobility spectrometry as a detection system for low
      density extraction solvent-based dispersive liquid-liquid microextraction.
AB  - This paper deals with a method based on negative corona discharge ionization ion
      mobility spectrometry (NCD-IMS) for the analysis of ethion (as an
      organophosphorus pesticide). The negative ions such as O2(-) and NO(x)(-) were
      eliminated from the background spectrum to increase the instrument sensitivity.
      The method was used to specify the sample extracted via dispersive liquid-liquid
      microextraction (DLLME) based on low density extraction solvent. The ion mobility
      spectrum of ethion in the negative mode and the reduced mobility value for its
      ion peak are firstly reported and compared with those of the positive mode. In
      order to combine the low density solvent DLLME directly with NCD-IMS, cyclohexane
      was selected as the extraction solvent, helping us to have a direct injection up
      to 20 uL solution, without any signal interference. The method was exhaustively
      validated in terms of sensitivity, enrichment factor, relative recovery, and
      repeatability. The linear dynamic range of 0.2-100.0 ug L(-1), detection limit of
      0.075 ug L(-1), and the relative standard deviation (RSD) of about 5% were
      obtained for the analysis of ethion through this method. The average recoveries
      were calculated about 68% and 92% for the grape juice and underground water,
      respectively. Finally, some real samples were analyzed and the feasibility of the
      proposed method was successfully verified by the efficient extraction of the
      analyte using DLLME before the analysis by NCD-IMS.

PMID- 25618729
TI  - Rapid detection of TNT in aqueous media by selective label free surface enhanced
      Raman spectroscopy.
AB  - We report rapid and ultra-sensitive detection system for 2,4,6-trinitrotoluene
      (TNT) using unmodified gold nanoparticles and surface-enhanced Raman spectroscopy
      (SERS). First, Meisenheimer complex has been formed in aqueous solution between
      TNT and cysteamine in less than 15 min of mixing. The complex formation is
      confirmed by the development of a pink colour and a new UV-vis absorption band
      around 520 nm. Second, the developed Meisenheimer complex is spontaneously self
      assembled onto unmodified gold nanoparticles through a stable Au-S bond between
      the cysteamine moiety and the gold surface. The developed mono layer of
      cysteamine-TNT is then screened by SERS to detect and quantify TNT. Our
      experimental results demonstrate that the SERS-based assay provide an ultra
      sensitive approach for the detection of TNT down to 22.7 ng/L. The unambiguous
      fingerprint identification of TNT by SERS represents a key advantage for our
      proposed method. The new method provides high selectivity towards TNT over 2,4
      DNT and picric acid. Therefore it satisfies the practical requirements for the
      rapid screening of TNT in real life samples where the interim 24-h average
      allowable concentration of TNT in waste water is 0.04 mg/L.

PMID- 25618730
TI  - Speciation of inorganic arsenic in drinking water by wavelength-dispersive X-ray
      fluorescence spectrometry after in situ preconcentration with miniature solid
      phase extraction disks.
AB  - A rapid and simple method using wavelength-dispersive X-ray fluorescence (WDXRF)
      spectrometry after in situ solid-phase extraction (SPE) was developed for the
      speciation and evaluation of the concentration of inorganic arsenic (As) in
      drinking water. The method involves the simultaneous collection of As(III) and
      As(V) using 13 mm phi SPE miniature disks. The removal of Pb(2+) from the sample
      water was first conducted to avoid the overlapping PbLalpha and AsKalpha spectra
      on the XRF spectrum. To this end, a 50 mL aqueous sample (pH 5-9) was passed
      through an iminodiacetate chelating disk. The filtrate was adjusted to pH 2-3
      with HCl, and then ammonium pyrrolidine dithiocarbamate solution was added. The
      solution was passed through a hydrophilic polytetrafluoroethylene filter placed
      on a Zr and Ca loaded cation-exchange disk at a flow rate of 12.5 mL min(-1) to
      separate As(III)-pyrrolidine dithiocarbamate complex and As(V). Each SPE disk was
      affixed to an acrylic plate using adhesive cellophane tape, and then examined by
      WDXRF spectrometry. The detection limits of As(III) and As(V) were 0.8 and 0.6
      MUg L(-1), respectively. The proposed method was successfully applied to
      screening for As speciation and concentration evaluation in spring water and well
      water.

PMID- 25618731
TI  - A new electrochemical sensor for the simultaneous determination of acetaminophen
      and codeine based on porous silicon/palladium nanostructure.
AB  - A porous silicon/palladium nanostructure was prepared and used as a new electrode
      material for the simultaneous determination of acetaminophen (ACT) and codeine
      (COD). Palladium nanoparticles were assembled on porous silicon (PSi)
      microparticles by a simple redox reaction between the Pd precursor and PSi in an
      aqueous solution of hydrofluoric acid. This novel nanostructure was characterized
      by different spectroscopic and electrochemical techniques including scanning
      electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy,
      fourier transform infrared spectroscopy and cyclic voltammetry. The high
      electrochemical activity, fast electron transfer rate, high surface area and good
      antifouling properties of this nanostructure enhanced the oxidation peak currents
      and reduced the peak potentials of ACT and COD at the surface of the proposed
      sensor. Simultaneous determination of ACT and COD was explored using differential
      pulse voltammetry. A linear range of 1.0-700.0 umol L(-1) was achieved for ACT
      and COD with detection limits of 0.4 and 0.3 umol L(-1), respectively. Finally,
      the proposed method was used for the determination of ACT and COD in blood serum,
      urine and pharmaceutical compounds.

PMID- 25618732
TI  - Effects of (R)- and (S)-propranolol hydrochloride enantiomers on the resonance
      Rayleigh scattering spectra with erythrosine B as probe and their analytical
      applications.
AB  - Propranolol, a chiral drug with two configurations, i.e., (R)-propranolol
      hydrochloride (RPH) and (S)-propranolol hydrochloride (SPH), has racemes that can
      be used in clinical diagnosis due to their synergistic effects. SPH has a beta
      receptor blocking effect, and RPH has an antiarrhythmic effect. In pH 4.6 Britton
      Robinson (BR) buffer solution, both RPH and SPH can react with erythrosine B to
      form 1:1 ion-association complexes. In the SPH-Ery B reaction system, a
      remarkable enhancement of the resonance Rayleigh scattering (RRS) signal located
      at 338 nm was observed. However, a similar phenomenon was not obvious and was
      unstable in the RPH-Ery B reaction system. Based on this result, a simple, novel
      and sensitive method for the determination of SPH was proposed based on the RRS
      technique. The linear range and limit of detection were 0.0680~4.0 ug mL(-1) and
      20.6 ng mL(-1), respectively. Additionally, the spectroscopic approaches of
      frequency doubling scattering (FDS) and second-order scattering (SOS) were also
      proposed for SPH detection in this article. The interaction information regarding
      the mechanism of the reaction, suitable reaction conditions, influencing factors
      and the effects of mixed solutions were our investigation aims. The method had
      been applied to the determination of SPH in fresh serum and urine samples of
      healthy human subjects with satisfactory results.

PMID- 25618733
TI  - Preparation of molecularly imprinted polymer with double templates for rapid
      simultaneous determination of melamine and dicyandiamide in dairy products.
AB  - In this study, a rapid and accurate determination strategy was established for
      simultaneous measurement of melamine (MLM) and dicyandiamide (DCD) directly in
      powdered milk by coupling molecularly imprinted solid-phase extraction (MISPE)
      with high performance liquid chromatography (HPLC). A novel double-template
      technique was adopted for preparing SPE packing agent and the obtained double
      templated (MLM and DCD) molecularly imprinted polymers (MD-MIPs) was
      characterized by Fourier-transform infrared spectroscopy and scanning electron
      microscope (SEM). The molecular recognition ability and the binding capability of
      the as-prepared polymers towards MLM and DCD were evaluated via static and
      dynamic binding tests, and it was found that the MD-MIPs showed better affinity
      and selectivity for both templates compared with single-templated MIPs and non
      imprinted polymers (NIPs). An approach based on MISPE and HPLC was then developed
      and optimized to detect MLM and DCD in powdered milk. The detection limit of the
      method (S/N=3) were 0.13 MUg/g for MLM and 0.07 MUg/g for DCD, and the relative
      standard deviation (RSD) of intra-day and inter-day determination for MLM was
      3.3% and 4.7%, and 3.5% and 5.9% for DCD. The recoveries in MLM and DCD analysis
      at three spiked levels were 93.1-100.1% and 75.7-82.5%, respectively, with all
      RSD less than 5.2%.

PMID- 25618734
TI  - Determination of sulfonamide antibiotics and metabolites in liver, muscle and
      kidney samples by pressurized liquid extraction or ultrasound-assisted extraction
      followed by liquid chromatography-quadrupole linear ion trap-tandem mass
      spectrometry (HPLC-QqLIT-MS/MS).
AB  - Sulfonamides are widely used in human and veterinary medicine. The presence of
      sulfonamides residues in food is an issue of great concern. Throughout the
      present work, a method for the targeted analysis of 16 sulfonamides and
      metabolites residue in liver of several species has been developed and validated.
      Extraction and clean-up has been statistically optimized using central composite
      design experiments. Two extraction methods have been developed, validated and
      compared: i) pressurized liquid extraction, in which samples were defatted with
      hexane and subsequently extracted with acetonitrile and ii) ultrasound-assisted
      extraction with acetonitrile and further liquid-liquid extraction with hexane.
      Extracts have been analyzed by liquid chromatography-quadrupole linear ion trap
      tandem mass spectrometry. Validation procedure has been based on the Commission
      Decision 2002/657/EC and included the assessment of parameters such as decision
      limit (CCalpha), detection capability (CCbeta), sensitivity, selectivity,
      accuracy and precision. Method's performance has been satisfactory, with CCalpha
      values within the range of 111.2-161.4 ug kg(-1), limits of detection of 10 ug
      kg(-1) and accuracy values around 100% for all compounds.

PMID- 25618735
TI  - Identifying clusters of falls-related hospital admissions to inform population
      targets for prioritising falls prevention programmes.
AB  - BACKGROUND: There has been limited research investigating the relationship
      between injurious falls and hospital resource use. The aims of this study were to
      identify clusters of community-dwelling older people in the general population
      who are at increased risk of being admitted to hospital following a fall and how
      those clusters differed in their use of hospital resources. METHODS: Analysis of
      routinely collected hospital admissions data relating to 45 374 fall-related
      admissions in Victorian community-dwelling older adults aged >=65 years that
      occurred during 2008/2009 to 2010/2011. Fall-related admission episodes were
      identified based on being admitted from a private residence to hospital with a
      principal diagnosis of injury (International Classification of Diseases (ICD)-10
      AM codes S00 to T75) and having a first external cause of a fall (ICD-10-AM codes
      W00 to W19). A cluster analysis was performed to identify homogeneous groups
      using demographic details of patients and information on the presence of
      comorbidities. Hospital length of stay (LOS) was compared across clusters using
      competing risks regression. RESULTS: Clusters based on area of residence,
      demographic factors (age, gender, marital status, country of birth) and the
      presence of comorbidities were identified. Clusters representing hospitalised
      fallers with comorbidities were associated with longer LOS compared with other
      cluster groups. Clusters delineated by demographic factors were also associated
      with increased LOS. CONCLUSIONS: All patients with comorbidity, and older women
      without comorbidities, stay in hospital longer following a fall and hence consume
      a disproportionate share of hospital resources. These findings have important
      implications for the targeting of falls prevention interventions for community
      dwelling older people.

PMID- 25618737
TI  - Method for determining individual deposition velocities of radon progeny.
AB  - The deposition velocity of radon progeny is used to model the removal of progeny
      from the air by surfaces in assessing indoor air quality. It can also be used to
      assess radon-induced background in sensitive, low-background experiments. A
      single value of the deposition velocity is typically used for all radon progeny
      for modeling purposes. This paper presents a method for uniquely determining the
      individual deposition velocities of radon progeny. Measurements demonstrating the
      method were carried out. 

PMID- 25618736
TI  - Synthesis, micellisation and interaction of novel quaternary ammonium compounds
      derived from l-Phenylalanine with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine as
      model membrane in relation to their antibacterial activity, and their selectivity
      over human red blood cells.
AB  - A series of quaternary ammonium compounds (QUATS) derived from l-Phenylalanine
      have been synthesized and their antibacterial efficiencies were determined
      against various strains of Gram-positive and Gram-negative bacteria. The
      antibacterial activity increased with increasing chain length, exhibiting a cut
      off effect at C14 for Gram-positive and C12 for Gram-negative bacteria. The l
      Phenylalanine QUATS displayed enhanced antibacterial properties with a higher cut
      off point compared to their corresponding l-Phenylalanine ester hydrochlorides.
      The CMC was correlated with the MIC, inferring that micellar activity contributes
      to the cut-off effect in antibacterial activity. The hemolytic activities (HC50)
      of the QUATS against human red blood cells were also determined to illustrate the
      selectivity of these QUATS for bacterial over mammalian cells. In general, the
      MIC was lower than the HC50, and assessment of the micellar contribution to the
      antibacterial and hemolytic evaluation in TBS as a common medium confirmed that
      these QUATS can act as antibacterial, yet non-toxic molecules at their monomer
      concentrations. The interaction of the QUATS with the phospholipid vesicles (1,2
      dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8
      naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as
      fluorescence probes showed that the presence of the quaternary ammonium moiety
      causes an increase in hydrophobic interactions, thus causing an increase in
      antibacterial activity. 

PMID- 25618738
TI  - [Reply].

PMID- 25618739
TI  - [Concurrent lymphoid and Philadelphia chromosome-negative myeloproliferative
      neoplasms].

PMID- 25618740
TI  - Essential role of TNF-alpha in development of spleen fibroblastic reticular
      cells.
AB  - TNF-alpha plays an important role in the development of secondary lymphoid
      tissues. Earlier studies showed that fibroblastic reticular cells express TNF
      alpha receptor, suggesting that TNF-alpha may affect the development of FRCs. To
      test this, we analyzed the development and function of FRCs in wild-type or TNF
      alpha knockout mice. We found that GP38 expression was down-regulated in the
      spleen of TNF-alpha knockout mice. Chemokines, mainly secreted by GP38(+) FRCs,
      were also down-regulated. Additionally, we found that absence of TNF-alpha
      decreased the homing ability to direct T cells to the spleen. However, absence of
      TNF-alpha did not affect the development of lymph nodes FRCs. These data reveal
      that TNF-alpha plays an important role in the development of spleen FRCs. Absence
      of TNF-alpha could cause abnormality of spleen FRCs, thereby weakening the homing
      ability of T cells to localize to the spleen T cell zone. 

PMID- 25618741
TI  - High rate of durable pulmonary vein isolation after second-generation cryoballoon
      ablation: analysis of repeat procedures.
AB  - AIMS: Pulmonary vein isolation (PVI) using the first-generation cryoballoon (CB1)
      was characterized by a high rate of recovered pulmonary vein (PV) conduction
      along with a typical conduction gap pattern in patients with recurrent atrial
      tachyarrhythmia (ATa). Second generation (CB2) enables more uniform freezing.
      However, the rate of chronic PVI and PV conduction gap pattern is unknown.
      METHODS AND RESULTS: All patients with ATa recurrence undergoing a second
      procedure after CB2 or (historical) CB1 PVI (28 mm) were enrolled. In all
      patients, a left atrial three-dimensional electronatomic reconstruction was
      performed. The rates of chronic PVI and localization of PV conduction gaps were
      determined and compared between CB1 and CB2. Antral PV re-isolation was performed
      using irrigated-tip radiofrequency current energy ablation. Of 206 patients
      (CB2), 18 patients underwent the repeat procedure after 192 (75:245) days. In 6
      of 18 (33%) patients, all PVs were electrically isolated whereas in the remaining
      12 patients (66%) at least one PV demonstrated PV reconduction. Of 71 PVs [1 left
      common PV (LCPV)], 55 PVs (77%) were chronically isolated. The right superior PV
      (RSPV) was characterized by the lowest rate of chronic PVI (RSPV: 56%, LSPV: 76%,
      RIPV: 83%, LIPV: 94%, LCPV: 100%). Compared with CB1, CB2 ablation resulted in a
      significantly higher rate of chronic PVI (CB2: 77% vs. CB1: 32%; P < 0.0001) with
      the greatest improvement along both inferior PVs. CONCLUSION: Second-generation
      cryoballoon atrial fibrillation ablation is associated with a high rate of
      durable PVI in patients with ATa recurrence. The RSPV represents the PV with the
      greatest risk for left atrium-pulmonary vein reconnection.

PMID- 25618742
TI  - Low contact force and force-time integral predict early recovery and dormant
      conduction revealed by adenosine after pulmonary vein isolation.
AB  - AIM: After pulmonary vein isolation (PVI), dormant conduction (DC) is present in
      at least one vein in a substantial number of patients. The present study seeks to
      determine whether there is a relationship between poor contact forces (CF) and
      the presence of DC after PVI. METHODS AND RESULTS: This prospective, operator
      blinded, non-randomized dual-centre trial enrolled 34 consecutive patients with
      paroxysmal atrial fibrillation who were candidates for PVI. Radiofrequency (RF)
      energy was delivered by using an irrigated-tip force-sensing ablation catheter
      (Tacticath, St Jude Medical) at pre-defined target power. The operators were
      blinded to the CF data at all times. A total of 1476 RF applications were
      delivered in 743 pre-defined PV segments. For each application, the precise
      location of the catheter was registered and the following data were extracted
      from the Tacisys unit: application duration, minimum contact force, maximum
      contact force, average contact force (CF), and force-time integral (FTI). Sixty
      minutes after PVI, spontaneous early recovery (ER) of the left atrium (LA) to PV
      conduction was evaluated. In the absence of ER, the presence of a DC was
      evaluated by using intravenous adenosine (ATP). In the 34 patients recruited (23
      males; mean age: 62 +/- 9 years), all PVs were successfully isolated. At the end
      of the 60 min waiting period, 22 patients demonstrated at least one spontaneous
      ER or DC under ATP. The mean CF and FTI per PV segment differed significantly
      among the different veins but the sites of ER and DC were evenly distributed.
      However, both the minimum, the first and the mean CF and FTI per PV segment were
      significantly lower in the PV segments presenting either ER or DC as compared
      with those without ER or DC (mean CF: 4.9 +/- 4.8 vs. 12.2 +/- 1.65 g and mean
      FTI: 297 +/- 291 vs. 860 +/- 81 g s, P < 0.001 for both). Using multivariate
      analysis, both the mean CF and the FTI per lesion remained significantly
      associated with the risk of ER or DC. Moreover, a CF < 5 g per PV segment
      predicted ER+ and DC+ with a sensitivity of 71% and specificity of 82%. In
      contrast, ER and DC were very unlikely if RF application was performed with a
      mean CF > 10 g (negative predictive value: 98.7%). CONCLUSION: Both a low CF and
      a low FTI are associated with the ER of the PVI and DC after PVI.

PMID- 25618743
TI  - Simultaneous isolation of superior and inferior pulmonary veins on both the left
      and right sides could yield better outcomes in patients with paroxysmal atrial
      fibrillation.
AB  - AIMS: This study investigated whether disappearance patterns of pulmonary vein
      (PV) potentials (PVPs) during PV isolation (PVI) affect the outcome of catheter
      ablation (CA) in patients with paroxysmal atrial fibrillation (PAF). METHODS AND
      RESULTS: Extensive PVI was performed in 1149 PAF patients (age, 61 +/- 10 years).
      Clinical and demographic characteristics, ablation data, and follow-up outcomes
      were prospectively collected. During an initial CA, simultaneous disappearance of
      superior and inferior PVPs in both right and left PVs was observed in 464 (40.4%)
      patients (Group S). Atrial fibrillation-recurrence free rates at 1, 3, and 5
      years after the initial CA in Group S were 78.9, 71.9, and 68.1%, respectively,
      which were higher than those in Group Non-S (P = 0.004). However, those were
      similar after the final CA between both groups. The incidence of PV-left atrium
      (LA) electrical reconnection was significantly lower in Group S than in Group Non
      S in the second (Group S, 65.6% vs. Group Non-S, 82.1%; P = 0.004) and third
      (Group S, 8.3% vs. Group Non-S, 47.6%; P = 0.03) CAs. Furthermore, the
      reconnections more frequently occurred on the side of PVs where simultaneous PVP
      elimination had not been achieved at the initial CA. Simultaneous disappearance
      of superior and inferior PVPs in both right and left PVs independently reduced
      the risk of AF recurrence after the initial CA by 26%. CONCLUSIONS: The
      simultaneous disappearance of superior and inferior PVPs in both right and left
      PVs is associated with less frequent PV-left atrium reconnection and may yield a
      better clinical outcome after the initial CA.

PMID- 25618744
TI  - Nuclear quadrupole coupling parameters and structural nature of the nonlinear
      optical material Li2B4O7 by NMR.
AB  - The structural nature underlying the nonlinear optical (NLO) properties of
      Li2B4O7 is characterized by nuclear magnetic resonance (NMR). The rotation
      patterns of (11)B NMR were measured. We observed sixteen different spectra which
      were divided into two groups, corresponding to two types of boron atoms, 4
      coordinated B(1) and 3-coordinated B(2), which have different boron-oxygen rings
      and lie at chemically inequivalent sites. From these results, the quadrupole
      parameter and the principal axis of the electric field gradient (EFG) tensor were
      determined for the two borons. 

PMID- 25618745
TI  - Psychometric properties of dual-task balance assessments for older adults: a
      systematic review.
AB  - BACKGROUND: The ability to maintain balance while simultaneously performing a
      cognitive task is essential for daily living and has been implicated as a risk
      factor of falls in older adults. AIMS: To evaluate the evidence related to the
      psychometric properties of dual-task balance assessments in older adults.
      METHODS: An extensive literature search of electronic databases was conducted.
      Articles were included if they evaluated the psychometric properties of dual-task
      balance assessment tools in older adults. The data were extracted by two
      independent researchers and confirmed with the principal investigator. The
      methodology quality of each study was rated by using the Consensus-based
      Standards for the Selection of Health Measurement Instruments (COSMIN) checklist.
      RESULTS: Twenty-six articles were included in this systematic review. For dual
      task static standing balance assessments, the center of pressure-related
      parameters (displacement, velocity) and reaction time measurements were reliable
      but not useful for prediction of falls. For walking balance assessments, the gait
      outcomes derived generally demonstrated good to excellent reliability (intraclass
      correlation coefficient >0.75), but their ability to predict falls varied.
      Outcomes derived from the cognitive tasks and the dual-task cost (dual-task
      performance minus single-task performance) mostly demonstrated low to fair
      reliability. The methodological quality of majority of studies was poor to fair,
      mainly due to small sample size. CONCLUSIONS: Among the dual-task balance
      assessments examined, the reliability and validity varied. The findings of this
      review should be useful in guiding the selection of dual-task balance measures in
      future research.

PMID- 25618746
TI  - 3D surgical planning in patients affected by lipodystrophy.
AB  - Lipodystrophy is a pathological condition characterized by the focal or general
      absence of adipose tissue. Surgeons reset the patient's surface contours using
      injectable materials to recreate a normal physical appearance. However, due to
      difficulties in preoperative planning and intraoperative assessment, about 15% of
      the surgical procedures involved are reinterventions to improve volume or
      symmetry. This increases the need for an available, efficient tool capable of
      providing the surgeon with a good estimation of the volumes to be injected before
      the intervention proper begins. This work describes a virtual reality-based
      application for the surgical planning of facial lipodystrophy correction (FLIC).
      The tool uses points selected interactively by the surgeon to compute a curve
      that delimits the surface area to be operated on. It then automatically computes
      an estimated natural reconstructed surface and the quantity of volume that needs
      to be implanted during the intervention. Experiments have been carried out in
      which the filling volumes estimated using FLIC and ZBrush software were compared
      with the real volumes injected by the surgeon. ICCs higher than 0.97 indicate
      that there were no significant differences between the respective measurements,
      thus validating the tool proposed in this paper. 

PMID- 25618748
TI  - Allele sharing at 12/15 STR loci between full siblings.

PMID- 25618747
TI  - Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2
      months predates and predicts atopic dermatitis at 1 year.
AB  - BACKGROUND: Loss-of-function mutations in the skin barrier protein filaggrin
      (FLG) are a major risk for atopic dermatitis (AD). The pathogenic sequence of
      disturbances in skin barrier function before or during the early development of
      AD is not fully understood. A more detailed understanding of these events is
      needed to develop a clearer picture of disease pathogenesis. A robust,
      noninvasive test to identify babies at high risk of AD would be important in
      planning early intervention and/or prevention studies. OBJECTIVES: To ascertain
      whether a noninvasive measurement of skin barrier function at day 2 after birth
      and at 2 months predicts the development of AD at 1 year. Furthermore, to
      determine whether increases in transepidermal water loss (TEWL) predate the
      development of clinical AD. METHODS: A total of 1903 infants were enrolled in the
      Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological
      and Nutritional Endpoints Birth Cohort study from July 2009 to October 2011.
      Measurements of TEWL were made at birth (day 2) and at 2 and 6 months. The
      presence of AD was ascertained at 6 and 12 months, and disease severity was
      assessed by using the SCORing Atopic Dermatitis clinical tool at 6 months and by
      using both the SCORing Atopic Dermatitis clinical tool and Nottingham Severity
      Score at 12 months. A total of 1300 infants were genotyped for FLG mutations.
      RESULTS: At 6 months, 18.7% of the children had AD, and at 12 months, 15.53%. In
      a logistic regression model, day 2 upper quartile TEWL measurement was
      significantly predictive of AD at 12 months (area under the receiver operating
      characteristic curve, 0.81; P < .05). Lowest quartile day 2 TEWL was protective
      against AD at 12 months. An upper quartile 2 month TEWL was also strongly
      predictive of AD at 12 months (area under the receiver operating characteristic
      curve, 0.84; P < .05). At both ages, this effect was independent of parental
      atopy, FLG status, or report of an itchy flexural rash at 2 months. Associations
      were increased when parental atopy status or child FLG mutation status was added
      into the linear regression model. CONCLUSIONS: Impairment of skin barrier
      function at birth and at 2 months precedes clinical AD. In addition to providing
      important mechanistic insights into disease pathogenesis, these findings have
      implications for the optimal timing of interventions for the prevention of AD.

PMID- 25618749
TI  - Experimental comparison of properties of natural and synthetic osmotic dilators.
AB  - PURPOSE: The in vitro study compares natural and synthetic osmotic dilators in
      selected parameters influencing their clinical efficacy. METHODS: Diameters of
      Laminaria and synthetic dilators (Dilapan-S and Dilasoft) were measured in dry
      state, during free swelling in isotonic solution and during swelling against a
      force. Three aspects were evaluated-diameter increase, speed of action and
      consistency of action. RESULTS: The maximum diameter increase of 3 and 4-mm
      Dilapan-S was 3.6 and 3.3 times, of Dilasoft 3.2 and 3.1 times, respectively. For
      Laminaria, it was 2.9 and 2.7 times. The difference between synthetic dilators
      and Laminaria was statistically significant (p < 0.01). Synthetic dilators also
      swelled faster. Under applied counter force, synthetic dilators increased their
      diameter more than Laminaria (+3.6 mm for Dilapan-S, +3.8 mm for Dilasoft, +1.2
      mm for Laminaria; p < 0.01) and achieved faster expansion. Synthetic dilators
      also showed significantly higher consistency between samples in all experiments.
      CONCLUSIONS: Synthetic dilators compared to Laminaria reached higher maximum
      diameters, acted faster, were more consistent and were able to expand against
      force three times more. The results support clinical observations that synthetic
      dilators are more suitable and preferable for same-day D&E procedure and that
      fewer synthetic dilators are needed to achieve the same effect.

PMID- 25618750
TI  - Prophylactic vitamin D supplementation in ovarian hyperstimulation syndrome: an
      animal study.
AB  - PURPOSE: To investigate the effect of vitamin D in ovarian hyperstimulation
      syndrome (OHSS). METHODS: In this animal study, 28 immature female Wistar rats
      were divided into four groups: group 1 (control); group 2 (ovarian stimulation);
      group 3 (OHSS group); group 4 (OHSS + vitamin D group). All groups were killed 48
      h after hCG administration and were compared in terms of vascular permeability,
      ovarian weight, ovarian diameter, vascular endothelial growth factor (VEGF)
      expression (immunohistochemistry) in ovarian tissue and pigment epithelium
      derived factor (PEDF) level in the serum (ELISA test) with the Kruskal-Wallis and
      Mann-Whitney U tests. RESULTS: VEGF expression in the vitamin D group was similar
      to that in the OHSS group. However, the PEDF level was significantly higher in
      the vitamin D group (p = 0.013). CONCLUSIONS: Prophylactic vitamin D
      supplementation is not sufficiently effective in preventing OHSS. Vitamin D
      effectively increases PEDF, which has an opposing effect on VEGF, which plays a
      key role in OHSS. Thus, the protective effect of Vitamin D on OHSS should be
      investigated with a vitamin D deficient model in the study group.

PMID- 25618751
TI  - Green biochemistry approach for synthesis of silver and gold nanoparticles using
      Ficus racemosa latex and their pH-dependent binding study with different amino
      acids using UV/Vis absorption spectroscopy.
AB  - Simple and eco-friendly biosynthesis approach was developed to synthesize silver
      nanoparticles (SNPs) and gold nanoparticles (GNPs) using Ficus racemosa latex as
      reducing agent. The presence of sunlight is utilized with latex and achieved the
      nanoparticles whose average size was in the range of 50-120 nm for SNPs and 20-50
      nm for GNPs. The synthesized nanoparticles were characterized by UV/Visible
      absorption spectroscopy, X-ray diffraction, and field emission-scanning electron
      microscopy techniques toget understand the obtained nanoparticles. The pH
      dependent binding studies of SNPs and GNPs with four amino acids, namely L
      lysine, L-arginine, L-glutamine and glycin have been reported. 

PMID- 25618752
TI  - Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine
      interrelationships in rheumatoid arthritis, coronary artery disease and
      peripheral artery occlusion disease.
AB  - Elevated circulating concentrations of total L-homocysteine (thCys) and free
      asymmetric dimethylarginine (ADMA) are long-established cardiovascular risk
      factors. Low circulating L-homoarginine (hArg) concentrations were recently found
      to be associated with increased cardiovascular morbidity and mortality. The
      biochemical pathways of these amino acids overlap and share the same cofactor S
      adenosylmethionine (SAM). In the present study, we investigated potential
      associations between hArg, L-arginine (Arg), ADMA and thCys in plasma of patients
      suffering from rheumatoid arthritis (RA), coronary artery disease (CAD) or
      peripheral artery occlusive disease (PAOD). In RA, we did not find any
      correlation between ADMA or hArg and thCys at baseline (n = 100) and after (n =
      83) combined add-on supplementation of omega-3 fatty acids, vitamin E, vitamin A,
      copper, and selenium, or placebo (soy oil). ADMA correlated with Arg at baseline
      (r = 0.446, P < 0.001) and after treatment (r = 0.246, P = 0.03). hArg did not
      correlate with ADMA, but correlated with Arg before (r = 0.240, P = 0.02) and
      after treatment (r = 0.233, P = 0.03). These results suggest that hArg, ADMA and
      Arg are biochemically familiar with each other, but unrelated to hCys in RA. In
      PAOD and CAD, ADMA and thCys did not correlate.

PMID- 25618753
TI  - Synthesis, resolution, and determination of absolute configuration of protected
      alpha-ethynylphenylalanine enantiomers.
AB  - Racemic-protected alpha-ethynylphenylalanine was synthesized from DL-2
      benzylserine using alpha-benzylserinal as key intermediate and was successfully
      resolved by HPLC on a chiral stationary phase at a semipreparative scale. The
      absolute configuration of both enantiomers was determined by vibrational circular
      dichroism.

PMID- 25618754
TI  - A (14)C-leucine absorption, distribution, metabolism and excretion (ADME) study
      in adult Sprague-Dawley rat reveals beta-hydroxy-beta-methylbutyrate as a
      metabolite.
AB  - Leucine is an essential branched-chain amino acid that acts as a substrate for
      protein synthesis and as a signaling molecule. Leucine not incorporated into
      muscle protein is ultimately oxidized through intermediates such as beta-hydroxy
      beta-methylbutyrate (HMB) which itself is reported to enhance muscle mass and
      function in rats and humans. HMB has been reported in the plasma following oral
      leucine administration in sheep and pigs but not in Sprague-Dawley rats, the
      standard preclinical model. Therefore, we conducted radiolabeled absorption,
      distribution, metabolism and excretion (ADME) studies in rats using a low (3
      mg/kg) or high dose (1,000 mg/kg) of (14)C-leucine. Blood, tissue, and urine
      samples were analyzed for (14)C-leucine and its metabolites by HPLC-MS. Our
      results show for the first time that (14)C-HMB appears in plasma and urine of
      rats following an oral dose of (14)C-leucine. (14)C-leucine appears in plasma as
      (14)C-alpha-ketoisocaproic acid (KIC) with a slower time course than (14)C-HMB, a
      putative product of KIC. Further, two novel metabolites of leucine were detected
      in urine, N-acetyl leucine and glycyl leucine. Mass balance studies demonstrate
      that excretory routes accounted for no more than 0.9 % of the radiolabel and
      approximately 61 % of the dose was recovered in the carcass. Approximately 65 %
      of the dose was recovered in total, suggesting that approximately one-third of
      the leucine dose is oxidized to CO2. In conclusion, this study demonstrates
      endogenous production of HMB from leucine in adult rats, a standard preclinical
      model used to guide design of clinical trials in nutrition.

PMID- 25618755
TI  - Continuous dry fermentation of swine manure for biogas production.
AB  - A down plug-flow anaerobic reactor (DPAR) was designed for the feasibility study
      on continuous dry fermentation of swine manure without any additional stirring.
      Using fresh swine manure as the feedstock with TS concentration (w/w) of 20%,
      25%, 30%, and 35%, stable volumetric biogas production rates of 2.40, 1.92,
      0.911, and 0.644L . (Ld)(-1) and biogas yields of 0.665, 0.532, 0.252, and 0.178
      L g(-)(1)VS were obtained respectively, and the TS degradation rates were 46.5%,
      45.4%, 53.2%, and 55.6%, respectively. With the increase of feedstock TS
      concentration, the concentration of ammonia nitrogen grew up to the maximum value
      of 3500 mg L(-1). Biogas production was obviously inhibited when the
      concentration of ammonia nitrogen was above 3000 mg L(-1). The maximal volumetric
      biogas production rate of 2.34 L .(Ld)(-1) and biogas yield of 0.649 L g(-1)VS
      were obtained with TS concentration of 25% at 25 degrees C without inhibition.
      Liquidity experiments showed that TS concentration of digestate could be less
      than 15.8%, and the flow rate of digestate more than 0.98 m s(-1) when the
      feedstock TS concentration was less than 35%, which indicated the digestate could
      be easily discharged from a DPAR. Therefore, it is feasible to conduct a
      continuous dry fermentation in a DPAR using fresh swine manure as the feedstock
      with TS concentration less than 35%, whereas the feedstock TS concentration
      should not exceed 30% to achieve the maximal biogas production rate and biogas
      yield.

PMID- 25618756
TI  - Dredged sediments as a resource for brick production: possibilities and barriers
      from a consumers' perspective.
AB  - A possible solution for the oversupply of dredged sediments is their use as a raw
      material in brick production. Despite the fact that several examples (e.g.,
      Agostini et al., 2007; Hamer and Karius, 2002; Xu et al., 2014) show that this
      application is feasible, some economic, technical and social limitations
      interfere with the development of a market of dredged materials in brick
      production in Flanders. While we describe the main characteristics of the supply
      side, we focus on the limitations and barriers from the demand side in the
      present study. Based on a consumers survey we analyze consumers' risk perceptions
      and attitudes towards bricks produced from dredged sediments. Consumers in
      Flanders are rather suspicious with respect to bricks produced from dredged
      sediments and their risk perception is mainly determined by the possibility of a
      bad bargain (brick of inferior quality) and the connotation with chemical
      contamination. The willingness to pay for bricks made from dredged sediments is
      mainly influenced by the age of the respondents, as well environmental awareness,
      and the respondents' belief in their ability to influence environmental problems.
      Sensitization and information of customers seems to be of primary importance to
      make dredged-sediment-derived bricks a successful product. 

PMID- 25618757
TI  - Erratum to: Prevalence and predictors of low bone density and fragility fractures
      in women with systemic lupus erythematosus in a Mediterranean region.

PMID- 25618759
TI  - A shotgun approach for the identification of platinum-protein complexes.
AB  - A shotgun approach including peptide-based OFFGEL-isoelectric focusing (IEF)
      fractionation has been developed with the aim of improving the identification of
      platinum-binding proteins in biological samples. The method is based on a filter
      aided sample preparation (FASP) tryptic digestion under denaturing and reducing
      conditions of cisplatin-, oxaliplatin-, and carboplatin-protein complexes,
      followed by OFFGEL-IEF separation of the peptides. Any risk of platinum loss is
      minimized throughout the procedure due to the removal of the reagents used after
      each stage of the FASP method and the absence of thiol-based reagents in the
      focusing buffer employed in the IEF separation. The platinum-peptide complexes
      stability after the FASP digestion and the IEF separation was confirmed by size
      exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP
      MS). The suitability of peptide-based OFFGEL-IEF fractionation for reducing the
      sample complexity for further nano-liquid chromatography-electrospray ionization
      tandem mass spectrometry (nLC-ESI-MS/MS) analysis has been demonstrated, allowing
      the detection of platinum-containing peptides, with significantly lower abundance
      and ionization efficiency than unmodified peptides. nLC-MS/MS analysis of
      selected OFFGEL-IEF fractions from tryptic digests with different complexity
      degrees: standard human serum albumin (HSA), a mixture of five proteins (albumin,
      transferrin, carbonic anhydrase, myoglobin, and cytochrome-c) and human blood
      serum allowed the identification of several platinum-peptides from cisplatin-HSA.
      Cisplatin-binding sites in HSA were elucidated from the MS/MS spectra and
      assessed considering the protein three-dimensional structure. Most of the
      potential superficial binding sites available on HSA were identified for all the
      samples, including a biologically relevant cisplatin-cross-link of two protein
      domains, demonstrating the capabilities of the methodology. 

PMID- 25618758
TI  - The impact of C677T and A1298C MTHFR polymorphisms on methotrexate therapeutic
      response in East Bohemian region rheumatoid arthritis patients.
AB  - Some single-nucleotide polymorphisms (SNPs) might be predictive of methotrexate
      (MTX) therapeutic outcome in rheumatoid arthritis (RA). The aim of this study was
      to determine whether SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene
      are predictive of MTX response. Comparison was made using EULAR response criteria
      and according to the change of DAS28 (?DAS28) after a 6-month MTX treatment in RA
      patient cohort. The two SNPs C677T (rs1801133) and A1298C (rs1801131) have been
      genotyped. A total of 120 patients were enrolled in the study, and all of them
      fulfilled the American College of Rheumatology 1987 RA criteria and are currently
      or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a
      combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping
      was performed using qPCR allelic discrimination. We did not found any association
      of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR
      1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0,
      respectively), or in recessive and codominant models. However, when ?DAS28 after
      a 6-month therapy was used as a measure of treatment efficacy, the 677CT and
      1298AC genotypes were found to be significantly associated with less favorable
      response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower
      ?DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means
      that a synergistic effect of 677CT and 1298AC genotypes was observed.
      Nevertheless, the DAS28 baseline was lower here comparing to other genotypes.
      Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in
      genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because
      these double-mutated homozygotes are known for their low MTHFR-specific activity.
      Global significance was P = 0.013, eta (2) = 0.160-i.e., large-size effect. Thus,
      our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to
      respond to MTX treatment. 

PMID- 25618760
TI  - Quantitative lysophospholipidomics in human plasma and skin by LC-MS/MS.
AB  - Lysophospholipids (LPLs) are an essential family of lipids, which serve as
      bioactive molecules and as precursors and intermediates of the
      glycerophospholipid and sphingolipid metabolisms. In this work we primarily
      focused on the subgroup lysoglycerophospholipids that comprise a polar headgroup
      at the sn-3 position and a fatty acyl group at either the sn-1 or sn-2 position
      of the glycerol backbone giving rise to the two potential regioisomers 1-acyl-2
      LPL and 2-acyl-1-LPL, respectively. We established a quantitative
      lysophospholipidomics method combining hydrophilic interaction chromatography
      (HILIC) with the scheduled multiple reaction monitoring (sMRM) algorithm for
      profiling a vast number of LPLs simultaneously, including the 1-acyl-2-LPL and 2
      acyl-1-LPL regioisomers. This approach facilitates baseline separation of
      monitored lipid classes and regioisomers, including sufficient separation of
      species having a different degree of unsaturation overcoming the overlapping
      effect of M + 2 isotopes. The lipid class-based separation improves the
      quantification of each molecular species as the internal standard elutes together
      with the endogenous species. The potential of this method is illustrated by
      analyzing LPLs from human plasma and skin samples. Altogether, 68 molecular lipid
      species, consisting of 110 regioisomers, were detected in plasma and 43 molecular
      lipids, consisting of 67 regioisomers, in skin samples. The novel skin LPL
      profile reveals that most of the lipid species exist as 2-acyl-1-LPL, in
      comparison to plasma where 1-acyl-2-LPLs are the dominant species.

PMID- 25618761
TI  - Subcellular-level resolution MALDI-MS imaging of maize leaf metabolites by MALDI
      linear ion trap-Orbitrap mass spectrometer.
AB  - A significant limiting factor in achieving high spatial resolution for matrix
      assisted laser desorption ionization-mass spectrometry (MALDI-MS) imaging is the
      size of the laser spot at the sample surface. Here, we present modifications to
      the beam-delivery optics of a commercial MALDI-linear ion trap-Orbitrap
      instrument, incorporating an external Nd:YAG laser, beam-shaping optics, and an
      aspheric focusing lens, to reduce the minimum laser spot size from ~50 MUm for
      the commercial configuration down to ~9 MUm for the modified configuration. This
      improved system was applied for MALDI-MS imaging of cross sections of juvenile
      maize leaves at 5-MUm spatial resolution using an oversampling method. A variety
      of different metabolites including amino acids, glycerolipids, and defense
      related compounds were imaged at a spatial resolution well below the size of a
      single cell. Such images provide unprecedented insights into the metabolism
      associated with the different tissue types of the maize leaf, which is known to
      asymmetrically distribute the reactions of C4 photosynthesis among the mesophyll
      and bundle sheath cell types. The metabolite ion images correlate with the
      optical images that reveal the structures of the different tissues, and
      previously known and newly revealed asymmetric metabolic features are observed. 

PMID- 25618762
TI  - Application of hydrostatic CCC-TLC-HPLC-ESI-TOF-MS for the bioguided
      fractionation of anticholinesterase alkaloids from Argemone mexicana L. roots.
AB  - A rapid hydrostatic counter-current chromatography-thin-layer chromatography
      electrospray-ionization time-of-flight mass spectrometry (CCC-TLC-ESI-TOF-MS)
      technique was established for use in seeking potent anti-Alzheimer's drugs among
      the acethylcholinesterase inhibitors in Argemone mexicana L. underground parts,
      with no need to isolate components in pure form. The dichloromethane extract from
      the roots of Mexican prickly poppy that was most rich in secondary metabolites
      was subjected to hydrostatic-CCC-based fractionation in descending mode, using a
      biphasic system composed of petroleum ether-ethyl acetate-methanol-water at the
      ratio of 1.5:3:2.1:2 (v/v). The obtained fractions were analyzed in a TLC-based
      AChE-inhibition "Fast Blue B" test. All active components in the fractions,
      including berberine, protopine, chelerithrine, sanguinarine, coptisine,
      palmatine, magnoflorine, and galanthamine, were identified in a direct TLC-HPLC
      ESI-TOF-MS assay with high accuracy. This is the first time galanthamine has been
      reported in the extract of Mexican prickly poppy and the first time it has been
      identified in any member of the Papaveraceae family, in the significant quantity
      of 0.77%.

PMID- 25618763
TI  - Hip resurfacing arthroplasty in treatment of avascular necrosis of the femoral
      head.
AB  - BACKGROUND: Hip resurfacing is a conservative type of total hip arthroplasty but
      its use is controversial, especially in patients with osteonecrosis. The aim of
      this study was analysis of the clinical and radiographic outcomes of hip
      resurfacing in patients with osteonecrosis. MATERIAL/METHODS: Between 2007 and
      2008, 30 hip resurfacing arthroplasties were performed due to osteoarthritis
      secondary to avascular necrosis of femoral head staged as Ficat III and IV.
      Patients were qualified to resurfacing arthroplasty when the extent of avascular
      necrosis using Kerboul's method was <200 degrees  and the angle between avascular
      necrosis and head-neck junction was >20 degrees . All patients were evaluated
      clinically and radiologically before and 60 months after the operation. RESULTS:
      The mean Harris Hip Score (HHS) score increased from 47.8 to 94.25 (p<0.05).
      Physical activity level (University of California, Los Angeles activity score-
      UCLA activity score) improved from 3.7 to 7.55 (p<0.05). No implant migration was
      observed. CONCLUSIONS: Management of osteonecrosis of the hip with resurfacing
      arthroplasty seems to be effective in strictly-selected patients.

PMID- 25618764
TI  - Dual-source computed tomography may define cardiac contusion in patients with
      blunt chest trauma in ED.
AB  - We report a 20-year-old woman with blunt chest trauma because of a motor vehicle
      injury who has traumatic asphyxia and hypotension. The diagnosis of blunt cardiac
      injury was put by using dual-energy computed tomography in the emergency
      department because other laboratory and imaging modalities were useless. After
      hospitalization in intensive care unit, she was treated with supportive and
      antiedema therapy. The patient was extubated on the fifth day and discharged on
      the ninth day without any sequel. Coexistence of traumatic asphyxia with blunt
      cardiac injury is rare. Several imaging techniques such as transthoracic and
      transesophageal echocardiography, contrast-enhanced multislice thorax computed
      tomography or initial electrocardiogram, and troponin I levels are used to detect
      the myocardial damage, but diagnostic capability is low. Dual-energy computed
      tomography is a promising new technology with the ability of defining blunt
      cardiac injuries and may have an indication in the emergency setting in patients
      with hemodynamic instability to rule in traumatic cardiac complications
      especially when electrocardiogram and transthoracic echocardiography are useless
      in the emergency department.

PMID- 25618765
TI  - An unusual complication of morbid obesity: epidural lipomatosis.

PMID- 25618766
TI  - "Right" ventricular assessment by cardiac magnetic resonance in Takotsubo
      cardiomyopathy.

PMID- 25618767
TI  - Parafalcine empyema, a tricky infectious cause of headache: a case report.
AB  - Headache caused by subdural empyema is usually associated with fever and symptoms
      and/or clinical signs of meningeal irritation and increased intracranial
      pressure. We describe a patient with headache with absence of these signs or
      symptoms of meningeal irritation or intracranial pressure, who turned out to have
      a parafalcine subduralempyema. A 28-year-old man had headache for 2 weeks, which
      had started with visual symptoms with duration of 5 minutes. Two days later, he
      developed fever. During these 2 weeks, he had recurrence of visual symptoms for 4
      times, with duration of several minutes.Neurologic examination at presentation on
      the emergency department showed no meningeal irritation or papilledema. However,
      on closer examination, a limited homonymous hemianopsia on the left side and a
      drift of the left leg were found. Magnetic resonance imaging showed parafalcine
      subdural empyema on the right side of the falx and a small brain abscess right
      occipitally. Neuronavigated craniotomy was performed, which confirmed the
      presence of empyema and allowed culture of the specimens. Streptococcus milleri
      group was cultured,which allowed narrowing of the antibiotic therapy to
      Benzylpenicillin12 million entities per 24 hours. Headache and subdural empyema
      diminished during treatment, and at follow-up 12 weeks after start of treatment,
      patient had no remaining complaints. Parafalcine-located subdural empyema can
      present without presence of clear localizing symptoms or signs like meningeal
      irritation and increased intracranial pressure. When headache is accompanied with
      fever, one should extensively question neurologic symptoms, and a thorough
      neurologic examination should be done.

PMID- 25618768
TI  - Timeliness of interfacility transfer for ED patients with ST-elevation myocardial
      infarction.
AB  - OBJECTIVES: Most US hospitals lack primary percutaneous coronary intervention
      (PCI) capabilities to treat patients with ST-elevation myocardial infarction
      (STEMI) necessitating transfer to PCI-capable centers. Transferred patients
      rarely meet the 120-minute benchmark for timely reperfusion, and referring
      emergency departments (EDs) are a major source of preventable delays. We sought
      to use more granular data at transferring EDs to describe the variability in
      length of stay at referring EDs. METHODS: We retrospectively analyzed a secondary
      data set used for quality improvement for patients with STEMI transferred to a
      single PCI center between 2008 and 2012. We conducted a descriptive analysis of
      the total time spent at each referring ED (door-in-door-out [DIDO] interval),
      periods that comprised DIDO (door to electrocardiogram [EKG], EKG-to-PCI
      activation, and PCI activation to exit), and the relationship of each period with
      overall time to reperfusion (medical contact-to-balloon [MCTB] interval).
      RESULTS: We identified 41 EDs that transferred 620 patients between 2008 and
      2012. Median MCTB was 135 minutes (interquartile range [IQR] 114,172). Median
      overall ED DIDO was 74 minutes (IQR 56,103) and was composed of door to EKG, 5
      minutes (IQR 2,11); EKG-to-PCI activation, 18 minutes (IQR 7,37); and PCI
      activation to exit, 44 minutes (IQR 34,56). Door-in door-out accounted for the
      largest proportion (60%) of overall MCTB and had the largest variability
      (coefficient of variability, 1.37) of these intervals. CONCLUSIONS: In this
      cohort of transferring EDs, we found high variability and substantial delays
      after EKG performance for patients with STEMI. Factors influencing ED decision
      making and transportation coordination after PCI activation are a potential
      target for intervention to improve the timeliness of reperfusion in patients with
      STEMI.

PMID- 25618769
TI  - Acoustic rhinometry in mouth breathing patients: a systematic review.
AB  - INTRODUCTION: When there is a change in the physiological pattern of nasal
      breathing, mouth breathing may already be present. The diagnosis of mouth
      breathing is related to nasal patency. One way to access nasal patency is by
      acoustic rhinometry. OBJECTIVE: To systematically review the effectiveness of
      acoustic rhinometry for the diagnosis of patients with mouth breathing. METHODS:
      Electronic databases LILACS, MEDLINE via PubMed and Bireme, SciELO, Web of
      Science, Scopus, PsycInfo, CINAHL, and Science Direct, from August to December
      2013, were consulted. 11,439 articles were found: 30 from LILACS, 54 from MEDLINE
      via Bireme, 5558 from MEDLINE via PubMed, 11 from SciELO, 2056 from Web of
      Science, 1734 from Scopus, 13 from PsycInfo, 1108 from CINAHL, and 875 from
      Science Direct. Of these, two articles were selected. RESULTS: The heterogeneity
      in the use of equipment and materials for the assessment of respiratory mode in
      these studies reveals that there is not yet consensus in the assessment and
      diagnosis of patients with mouth breathing. CONCLUSION: According to the
      articles, acoustic rhinometry has been used for almost twenty years, but
      controlled studies attesting to the efficacy of measuring the geometry of nasal
      cavities for complementary diagnosis of respiratory mode are warranted.

PMID- 25618770
TI  - Exploring culturally and linguistically diverse consumer needs in relation to
      medicines use and health information within the pharmacy setting.
AB  - BACKGROUND: Low health literacy may result in adverse health outcomes for
      patients and is a problem faced by countries with multi-ethnic demography. For
      those of culturally and linguistically diverse (CALD) backgrounds, this problem
      can be compounded by language barriers such as low English proficiency (LEP). The
      pharmacy is often the last point of health-care provider contact before patients
      begin taking their medicines and the first point of care for minor ailments.
      There is a paucity of data exploring or establishing the needs of this population
      with respect to general medicine use/health information and pharmacist
      assistance. OBJECTIVE: This study aimed to investigate the needs of CALD
      Australians with low or negligible English proficiency, specifically in regards
      to their understanding of health and medicines and the role of pharmacy in
      achieving best medicine use outcomes for this population. METHODS: A qualitative
      method was employed. Semi-structured interviews were conducted with individuals
      of CALD backgrounds with a self-reported low or negligible English proficiency.
      The interviews explored past experiences with medicines use and interaction with
      health care professionals. A grounded theory approach with the method of constant
      comparison was undertaken for analyzing the data. Interviews were conducted until
      there was a saturation of themes. RESULTS: Thirty-one interviews were conducted,
      and data analyses identified themes relating to medicine use of CALD community
      members which were broadly categorized into: (1) health information, (2)
      interactions with health care professionals, (3) social networks and (4)
      perceptions and beliefs influencing health-related behavior. CONCLUSIONS: In CALD
      communities there are significant barriers to patient understanding and optimal
      use of medicines. There is significant potential for pharmacy to facilitate in
      addressing these issues as currently pharmacy is largely playing the role of
      dispenser of medicines. Whilst timely access of medicines is being ensured, there
      seems to be ample room for improvement in terms of pharmacy's role in
      facilitating appropriate and efficacious use of medicines with such CALD
      community members.

PMID- 25618771
TI  - Efficacy of transcutaneous interferential electrical stimulation in treatment of
      children with primary nocturnal enuresis: a randomized clinical trial.
AB  - BACKGROUND: Electrical stimulation has been used as an alternative therapy for
      adult urinary syndromes and for children with constipation. We have evaluated the
      safety and efficacy of interferential (IF) electrical stimulation in children
      with nocturnal enuresis (NE). METHODS: This was a randomized clinical trial in
      which 54 children (23 girls, 31 boys) aged 6-14 years with primary NE were
      recruited and randomly divided into two groups. Children in the control group
      underwent standard urotherapy only (hydration, scheduled voiding, toilet
      training, diet), whereas children in the IF group (cases) were treated with
      standard urotherapy + 15 sessions of IF electrical stimulation for 20 min twice
      per week. An improvement score was calculated to identify relative decrease in
      wet nights after the treatment for each child. All children were followed for 1
      year. RESULTS: Overall, 15/27 (55.5%) and 6/27 (22%) of children in the IF and
      control groups responded to treatment at the 1-year follow-up (P = 0.01). The
      mean number of wet nights per week in the control and IF groups decreased from
      5.4 +/- 2 and 5.7 +/- 2 to 3.3 +/- 3 and 1.1 +/- 2, respectively, at first
      evaluation (P = 0.003). The mean improvement score in the IF group was
      significantly higher than that of the control group after 1 year (78 vs. 46%,
      respectively; P = 0.004). CONCLUSION: Interferential therapy can be applied as a
      safe, effective and well-tolerable alternative therapy in the treatment of
      children with NE.

PMID- 25618773
TI  - Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus.
AB  - Much research in reproductive immunology is preoccupied with maternal tolerance
      of the semi-allogeneic fetus. This inevitably leads to the assumption that the
      maternal immune system should be suppressed, similarly to the immunosuppression
      needed to avoid rejection of an allograft. However, the parallels with
      transplantation immunology are misleading, and we discuss how interactions
      between variable immune system genes expressed on maternal natural killer (NK)
      cells and on the fetal trophoblast modulate fetal growth. Exaggerated suppression
      or activation of maternal NK cells associates with both extremes of birth weight.

PMID- 25618772
TI  - Interactions of vitamin D and the proximal tubule.
AB  - Severe vitamin D deficiency (reduction in serum 25(OH)D concentration) in infants
      and children can cause features of the Fanconi syndrome, including phosphaturia,
      glycosuria, aminoaciduria, and renal tubular acidosis. This indicates that
      vitamin D and its metabolites influence proximal tubule function. Filtered
      25(OH)D bound to vitamin D binding protein (DBP) is endocytosed by megalin
      cubilin in the apical membrane. Intracellular 25(OH)D is metabolized to
      1,25(OH)2D or calcitroic acid by 1-alpha-hydroxylase or 24-hydroxylase in tubule
      cell mitochondria. Bone-produced fibroblast growth factor 23 (FGF23) bound to
      Klotho in tubule cells and intracellular phosphate concentrations are regulators
      of 1-alpha-hydroxylase activity and cause proximal tubule phosphaturia.
      Aminoaciduria occurs when amino acid transporter synthesis is deficient, and
      1,25(OH)2D along with retinoic acid up-regulate transporter synthesis by a
      vitamin D response element in the promoter region of the transporter gene. This
      review discusses evidence gained from studies in animals or cell lines, as well
      as from human disorders, that provide insight into vitamin D-proximal tubule
      interactions. 

PMID- 25618774
TI  - Molecular drivers of cellular metabolic reprogramming in melanoma.
AB  - The development of metastatic melanoma is accompanied by distinct changes in
      cellular metabolism, most notably a change in strategy for energy production from
      mitochondrial oxidative phosphorylation to cytoplasmic aerobic glycolysis. This
      bioenergetic switch occurs at the expense of less-efficient utilization of
      glucose, but is required for melanoma cells to meet their bioenergetic and
      biosynthetic demands. Recent work has implicated well-established melanoma
      drivers such as BRAF, PTEN, MITF, and ARF in the regulation of cellular energy
      metabolism. The metabolic changes in melanoma cells offer new opportunities for
      therapeutic intervention. However, inter- and intratumor bioenergetic
      heterogeneity caused by variation in genetic driver profiles and mitochondrial
      performance may impact on the effectiveness of treatment. 

PMID- 25618775
TI  - Noninvasive fetal genomic, methylomic, and transcriptomic analyses using maternal
      plasma and clinical implications.
AB  - The discovery of cell-free fetal DNA in maternal plasma opened up new
      possibilities for noninvasive prenatal testing (NIPT). Conceptual advances in
      single-molecule counting have resulted in robust methods for the NIPT of fetal
      chromosomal aneuploidies and subchromosomal aberrations. Such methods are
      employed worldwide and are among the most rapidly adopted genomic tests.
      Furthermore, approaches for fetal whole-genome sequencing from maternal plasma,
      as well as for targeted detection of many single-gene disorders, have been
      reported. Recently, fetal methylome and transcriptome sequencing from maternal
      plasma have also been achieved, potentially allowing fetal physiological and
      pathological processes to be monitored noninvasively using maternal blood. These
      advances herald exciting future applications in prenatal medicine. 

PMID- 25618776
TI  - Nationwide survey of the development of drug resistance in the pediatric field in
      2007, 2010, and 2012: drug sensitivity of Haemophilus influenzae serotype b
      strain in Japan.
AB  - Based on the results of surveillance in the pediatric field conducted in 2007,
      2010, and 2012, we examined the frequency of Haemophilus influenzae serotype b
      (Hib) strains, the susceptibility for Hib strains to various types of
      antimicrobial agent, and the relations to patients' background factors. Among all
      of Haemophilus influenzae, the frequency of Hib strains was 3.6% (14/386 strains)
      in 2007, 4.8% (23/484 strains) in 2010, 1.2% (5/411 strains) in 2012, and
      decreasing in 2012. Hib strains were isolated in patients with the following
      infections: nine patients with respiratory tract infections (upper respiratory
      tract infection, bronchitis, and pneumonia), three patients with sepsis, one
      patient with meningitis, and one patient with purulent inflammation of a tendon
      sheath in 2007; 11 patients with respiratory tract infections (upper respiratory
      tract infection, bronchitis, and pneumonia), four patients with sepsis, and eight
      patients with meningitis in 2010, demonstrating a relatively high frequency in
      patients with invasive infections. However, in 2012, Hib strains were isolated in
      only four patients with respiratory tract infections (upper respiratory tract
      infection) and one patient with bronchial asthma. Evaluation of background
      factors with pediatric patients in whom Hib strains were isolated showed that
      approximately 70% were male; majority was children under three years of age; and
      higher detection rates were also related to the background of patients who were
      attendant to daycare center, had siblings, had received no antimicrobial agents
      within the previous one month before collecting specimens. Throughout the
      surveillance between 2007 and 2012, antimicrobial agents with all phases' MICs <=
      1 MUg/mL were cefditoren, cefcapene, and cefteram in the oral beta-lactams;
      tazobactam/piperacillin, ceftriaxone, cefotaxime, and meropenem in the injectable
      beta-lactams; azithromycin in the macrolide; and levofloxacin in the quinolone.
      After 2010, MIC ranges were evaluated for tebipenem in the oral beta-lactam (<=
      0.063-0.25 MUg/mL), doripenem in the injectable beta-lactam (<= 0.063-0.5
      MUg/mL), and tosufloxacin in the quinolone (<= 0.063 MUg/mL). Throughout the
      surveillance, Hib strains were highly susceptible to the above mentioned
      antimicrobial agents, and there was no significant change in the susceptibility.

PMID- 25618777
TI  - The change of macrolide resistance rates in group A Streptococcus isolates from
      children between 2002 and 2013 in Asahikawa city.
AB  - This study targeted patients in the Department of Pediatrics, Asahikawa Kosei
      Hospital, between January 2002 and December 2013. In patients suspected of having
      hemolytic streptococcal infection, Group A Streptococcus (GAS) strains isolated
      from a throat swab were examined for antimicrobial susceptibility testing. The
      MICs were measured by the broth microdilution method. The annual number of GAS
      strains examined for antimicrobial susceptibility testing ranged from 28 to 65
      strains, for a total of 574 strains. Some of the isolates obtained from 2006 to
      2009 and from 2011 to 2013 were analyzed to determine their emm types. An
      erythromycin (EM) resistant strain was not detected until 2004, but one EM
      resistant strain appeared in 2005. Subsequently, EM-resistant strains rapidly
      increased, and 48 of 65 strains (73.8%) examined in 2009 were resistant. In 2010,
      the number of EM-resistant strains decreased to 12 of 36 strains (33.3%).
      However, it gradually increased afterwards, and 37 of 60 strains (61.7%) were
      resistant in 2013. Out of 574 strains examined, 184 exhibited EM-resistance, and
      the overall resistance rate was 31.9%. Partitioning the 124 strains examined
      between 2006 and 2008 according to emm types, only emm28 strains, which exhibited
      a high resistance rate, and emm12 strains demonstrated resistance. For the 142
      strains examined between 2011 and 2013, the resistance rate of emm28 strains was
      similarly high; the resistance of emm12 strains significantly increased, and emm1
      strains exhibited a high resistance rate. The number of emm types associated with
      the resistant strains increased. 

PMID- 25618778
TI  - Ezrin-related Phosphoinositide pathway modifies RhoA and Rac1 in human
      osteosarcoma cell lines.
AB  - Selected Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes occupy the
      convergence point of the broad range of pathways that promote Rho and Ras GTPase
      mediated signalling, which also regulate the activation of ezrin, a member of the
      ezrin-radixin-moesin (ERM) proteins family involved in the metastatic
      osteosarcoma spread. Previous studies described that in distinct human
      osteosarcoma cell lines ezrin networks the PI-PLC with complex interplay
      controlling the expression of the PLC genes, which codify for PI-PLC enzymes. In
      the present study, we analyzed the expression and the sub-cellular distribution
      of RhoA and Rac1 respectively after ezrin silencing and after PI-PLC epsilon
      silencing, in order to investigate whether ezrin-RhoGTPAses signalling might
      involve one or more specific PI-PLC isoforms in cultured 143B and Hs888 human
      osteosarcoma cell lines. In the present experiments, both ezrin and PLCE gene
      silencing had different effects upon RhoA and Rac1 expression and sub-cellular
      localization. Displacements of Ezrin and of RhoA localization were observed,
      probably playing functional roles. 

PMID- 25618779
TI  - Clinical usefulness and economic implications of continuation/maintenance
      electroconvulsive therapy in a Spanish National Health System public hospital: A
      case series.
AB  - INTRODUCTION: Continuation/maintenance electroconvulsive therapy has been shown
      to be effective for prevention of relapse in affective and psychotic disorders.
      However, there is a limited nubber of studies that investigate clinical
      management, associated costs, and perceived quality variables. MATERIAL AND
      METHODS: A series of 8 cases included during the first 18 months of the
      Continuation/Maintenance Electroconvulsive Therapy Program of the Psychiatry
      Department at 12 de Octubre University Hospital is presented. Clinical variables
      (Clinical Global Impression-Improvement Scale, length of hospitalization, number
      of Emergency Department visits, number of urgent admissions) before and after
      inclusion in the continuation/maintenance electroconvulsive therapy program were
      compared for each patient, as well as associated costs and perceived quality.
      RESULTS: After inclusion in the program, 50.0% of patients reported feeling "
      much better " and 37.5% " moderately better " in the Clinical Global Impression
      Improvement Scale. In addition, after inclusion in the continuation/maintenance
      electroconvulsive therapy program, patients were hospitalized for a total of 349
      days, visited the Emergency Department on 3 occasions, and had 2 urgent
      admissions, compared to 690 days of hospitalization (P = .012), 26 Emergency
      Department visits (P = .011) and 22 urgent admissions (P = .010) during the same
      period before inclusion in the program. Associated direct costs per day of
      admission were reduced to 50.6% of the previous costs, and costs associated with
      Emergency Department visits were reduced to 11.5% of the previous costs. As
      regards perceived quality, 87.5% of patients assessed the care and treatment
      received as being " very satisfactory ", and 12.5% as " satisfactory ".
      CONCLUSIONS: This continuation/maintenance electroconvulsive therapy program has
      shown to be clinically useful and to have a favourable economic impact, as well
      as high perceived quality.

PMID- 25618780
TI  - Laparoscopic hand-sewn revisional gastrojejunal plication for weight loss failure
      after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Revisional surgery has become a widely accepted alternative for
      weight loss failure/regain after bariatric surgery. However, it is associated to
      higher morbi-mortality and lesser weight loss than primary bariatric procedure.
      Our aims are to present a novel technique for weight loss treatment after failed
      laparoscopic Roux-en-Y gastric bypass (LRYGB) and to report its short-term
      results. METHODS: This is a retrospective analysis of patients submitted to a
      revisional hand-sewn double-layer gastrojejunal plication (GJP) for treatment of
      weight loss failure/regain after LRYGB. Analysis of demographics, body mass index
      (BMI), and percentage of excess weight loss (%EWL) at the 6th month
      complications, and financial costs involved was included. RESULTS: Four patients
      were submitted to revisional GJP. Three patients were female and the mean age at
      revision was 30 +/- 9 years (21-44). The median time interval between LRYGB and
      GJP was 51 months (24-120). The median BMI at the moment of GJP and the 3rd and
      6th month was 35.6 kg/m2 (32.0-37.8), 32.2 kg/m2 (29.7-34.1), and 30.7 kg/m2
      (28.1-32.1), respectively. The median %EWL at the 3rd and 6th month was 35.4%
      (13.6-38.9) and 46.2 % (45.1-55.5), respectively, reaching a cumulative (combined
      surgeries) %EWL of 62.9% (16.5-67.9) and 71.7% (65.1-77.6), respectively. There
      were no complications or mortality. Financial costs were significantly lower
      compared to revisional gastrojejunal stapled reduction (US $1400 cheaper).
      CONCLUSION: Revisional GJP is a feasible, safe, and cost-effective novel
      procedure for treatment of weight loss failure/regain after LRYGB. Mid- and long
      term results are necessary in order to establish its real effectiveness.

PMID- 25618781
TI  - Airway Hyperresponsiveness to Mannitol in Obesity Before and After Bariatric
      Surgery.
AB  - BACKGROUND: The relationship between airway hyperresponsiveness (AHR) and
      obesity, a low-grade systemic inflammatory condition, remains largely unknown. It
      is established that AHR to indirect stimuli is associated with active airway
      inflammation. The objectives were to investigate the rate of AHR to mannitol in
      obese subjects and its changes 1 year after bariatric surgery (BS). METHODS: We
      enrolled 58 candidates to BS severely obese (33 nonsmokers and 25 smokers)
      without history of asthma and 20 healthy, nonobese participants and related AHR
      to functional findings and serum and exhaled biomarkers. RESULTS: Before surgery,
      AHR was observed in 16 (28 %) obese with the provocation doses of mannitol to
      induce a 15 % fall in FEV1 (PD15) of (geometric mean [95 % CI]) 83 (24-145) mg.
      Compared to control participants, obese participants had lower spirometric values
      and higher serum and exhaled biomarkers (p < 0.05 each). After surgery, AHR was
      abolished (p < 0.01) in all but four obese subjects. CONCLUSIONS: Weight loss
      induced by BS was the key independent factor associated to AHR improvement. AHR
      to mannitol is highly prevalent in obesity, and it is largely abolished by BS.

PMID- 25618782
TI  - Dynamic collimator angle adjustments during volumetric modulated arc therapy to
      account for prostate rotations.
AB  - PURPOSE: Rotations of the prostate gland induce considerable geometric
      uncertainties in prostate cancer radiation therapy. Collimator and gantry angle
      adjustments can correct these rotations in intensity modulated radiation therapy.
      Modern volumetric modulated arc therapy (VMAT) treatments, however, include a
      wide range of beam orientations that differ in modulation, and corrections
      require dynamic collimator rotations. The aim of this study was to implement a
      rotation correction strategy for VMAT dose delivery and validate it for left
      right prostate rotations. METHODS AND MATERIALS: Clinical VMAT treatment plans of
      5 prostate cancer patients were used. Simulated left-right prostate rotations
      between +15 degrees  and -15 degrees  were corrected by collimator rotations. We
      compared corrected and uncorrected plans by dose volume histograms, minimum dose
      (Dmin) to the prostate, bladder surface receiving >=78 Gy (S78) and rectum
      equivalent uniform dose (EUD; n=0.13). Each corrected plan was delivered to a
      phantom, and its deliverability was evaluated by gamma-evaluation between planned
      and delivered dose, which was reconstructed from portal images acquired during
      delivery. RESULTS: On average, clinical target volume minimum dose (Dmin)
      decreased up to 10% without corrections. Negative left-right rotations were
      corrected almost perfectly, whereas Dmin remained within 4% for positive
      rotations. Bladder S78 and rectum EUD of the corrected plans matched those of the
      original plans. The average pass rate for the corrected plans delivered to the
      phantom was 98.9% at 3% per 3 mm gamma criteria. The measured dose in the
      planning target volume approximated the original dose, rotated around the
      simulated left-right angle, well. CONCLUSIONS: It is feasible to dynamically
      adjust the collimator angle during VMAT treatment delivery to correct for
      prostate rotations. This technique can safely correct for left-right prostate
      rotations up to 15 degrees .

PMID- 25618783
TI  - Role of coherent vibrations in energy transfer and conversion in photosynthetic
      pigment-protein complexes.
AB  - Oscillatory features of two-dimensional spectra of photosynthetic pigment-protein
      complexes during few picoseconds after electronic excitations of chlorophylls in
      various pigment-proteins were recently related to the coherent nuclear
      vibrations. It has been also speculated that the vibrations may assist the
      excitonic energy transfer and charge separation, hence contributing to energy
      transport and energy conversion efficiency. Here, we consider three theoretical
      approaches usually used for characterization of the excitation dynamics and
      charge separation, namely Redfield, Forster, and Marcus model descriptions,
      regarding this question. We show that two out of the three mechanisms require
      explicit resonances of excitonic splittings and the nuclear vibration
      frequencies. However, the third one related to the electron transfer is in
      principle off resonant. 

PMID- 25618785
TI  - Disulfiram and the Zenalyser(r): teaching an old dog new tricks.

PMID- 25618786
TI  - Streptomyces violaceoruber phospholipase A2: expression in Pichia pastoris,
      properties, and application in oil degumming.
AB  - The phospholipase A2 (PLA2) from Streptomyces violaceoruber was successfully
      expressed in the methylotrophic yeast Pichia pastoris GS115 under the control of
      AOX1 promoter for the first time. The maximum activity of the recombinant PLA2
      (rPLA2) reached 34.7 +/- 0.2 U/mL, and specific activity was 170 +/- 4 U/mg after
      purification. On the sodium dodecyl sulfate polyacrylamide gel electrophoresis of
      the culture supernatants, three bands of 21, 18, and 14.3 kDa were observed. The
      peptide mass fingerprinting analysis showed that all of these three bands were
      rPLA2 from S. violaceoruber. By the treatment with Endo H and PNGase F, it
      indicated that the rPLA2 occurred N-glycosylation. The enzymatic properties of
      this enzyme were determined. The rPLA2 exhibited a lower optimum pH (pH = 6.0)
      compared to the wild-type enzyme, which was a desirable property in the
      application of oil degumming. In the enzymatic degumming process, the phosphorus
      content decreased from 261.77 +/- 3.51 mg/kg to 20.74 +/- 0.23 mg/kg, which is
      very promising for the industrial application.

PMID- 25618787
TI  - Effect of esomeprazole on gastroduodenal erosions in patients at increased
      gastrointestinal risk treated with low-dose acetylsalicylic acid: a post-hoc
      analysis of the OBERON trial.

PMID- 25618784
TI  - Potential contributions of the tobacco nicotine-derived nitrosamine ketone (NNK)
      in the pathogenesis of steatohepatitis in a chronic plus binge rat model of
      alcoholic liver disease.
AB  - AIMS: Alcoholic liver disease (ALD) is linked to binge drinking and cigarette
      smoking. Heavy chronic +/- binge alcohol, or low-level exposures to dietary
      nitrosamines cause steatohepatitis with insulin resistance and oxidative stress
      in animal models. This study examines hepatotoxic effects of sub-mutagenic
      exposures to tobacco-specific nitrosamine (NNK) in relation to ALD. METHODS: Long
      Evans rats were fed liquid diets containing 0 or 26% (caloric) ethanol (EtOH) for
      8 weeks. In Weeks 3 through 8, rats were treated with NNK (2 mg/kg) or saline by
      i.p. injection, 3*/week, and in Weeks 7 and 8, EtOH-fed rats were binge
      administered 2 g/kg EtOH 3*/week; controls were given saline. RESULTS: EtOH +/-
      NNK caused steatohepatitis with necrosis, disruption of the hepatic cord
      architecture, ballooning degeneration, early fibrosis, mitochondrial cytopathy
      and ER disruption. Severity of lesions was highest in the EtOH+NNK group. EtOH
      and NNK inhibited insulin/IGF signaling through Akt and activated pro
      inflammatory cytokines, while EtOH promoted lipid peroxidation, and NNK increased
      apoptosis. O(6)-methyl-Guanine adducts were only detected in NNK-exposed livers.
      CONCLUSION: Both alcohol and NNK exposures contribute to ALD pathogenesis,
      including insulin/IGF resistance and inflammation. The differential effects of
      EtOH and NNK on adduct formation are critical to ALD progression among alcoholics
      who smoke.

PMID- 25618789
TI  - Balance Sheets Versus Decision Dashboards to Support Patient Treatment Choices: A
      Comparative Analysis.
AB  - BACKGROUND: Growing recognition of the importance of involving patients in
      preference-driven healthcare decisions has highlighted the need to develop
      practical strategies to implement patient-centered shared decision-making. The
      use of tabular balance sheets to support clinical decision-making is well
      established. More recent evidence suggests that graphic, interactive decision
      dashboards can help people derive deeper a understanding of information within a
      specific decision context. We therefore conducted a non-randomized trial
      comparing the effects of adding an interactive dashboard to a static tabular
      balance sheet on patient decision-making. METHODS: The study population consisted
      of members of the ResearchMatch registry who volunteered to participate in a
      study of medical decision-making. Two separate surveys were conducted: one in the
      control group and one in the intervention group. All participants were instructed
      to imagine they were newly diagnosed with a chronic illness and were asked to
      choose between three hypothetical drug treatments, which varied with regard to
      effectiveness, side effects, and out-of-pocket cost. Both groups made an initial
      treatment choice after reviewing a balance sheet. After a brief "washout" period,
      members of the control group made a second treatment choice after reviewing the
      balance sheet again, while intervention group members made a second treatment
      choice after reviewing an interactive decision dashboard containing the same
      information. After both choices, participants rated their degree of confidence in
      their choice on a 1 to 10 scale. RESULTS: Members of the dashboard intervention
      group were more likely to change their choice of preferred drug (10.2 versus
      7.5%; p = 0.054) and had a larger increase in decision confidence than the
      control group (0.67 versus 0.075; p < 0.03). There were no statistically
      significant between-group differences in decisional conflict or decision aid
      acceptability. CONCLUSION: These findings suggest that clinical decision
      dashboards may be an effective point-of-care decision-support tool. Further
      research to explore this possibility is warranted.

PMID- 25618790
TI  - The Predictive Value of Discrete Choice Experiments in Public Health: An
      Exploratory Application.
AB  - OBJECTIVE: The objective of this study was to assess the predictive value of a
      discrete choice experiment (DCE) in public health by comparing stated preferences
      to actual behavior. METHODS: 780 Type 2 diabetes mellitus (T2DM) patients
      received a questionnaire, containing a DCE with five attributes related to T2DM
      patients' willingness to participate in a combined lifestyle intervention. Panel
      mixed-multinomial-logit models were used to estimate the stated preferences based
      on 206 completed DCE questionnaires. Actual participation status was retrieved
      for 54 respondents based on patients' medical records and a second questionnaire.
      Predicted and actual behavior data were compared at population level and at
      individual level. RESULTS: Based on the estimated utility function, 81.8% of all
      answers that individual respondents provided on the choice tasks were predicted
      correctly. The actual participation rate at the aggregated population level was
      minimally underestimated (70.1 vs. 75.9%). Of all individual choices, 74.1% were
      predicted correctly with a positive predictive value of 0.80 and a negative
      predictive value of 0.44. CONCLUSION: Stated preferences derived from a DCE can
      adequately predict actual behavior in a public health setting.

PMID- 25618791
TI  - Three months of strictly controlled daily endurance exercise reduces thrombin
      generation and fibrinolytic risk markers in younger moderately overweight men.
AB  - PURPOSE: Physical activity is associated with a decreased risk of cardiovascular
      disease, but dose dependency of long-term physical exercise on biomarkers within
      coagulation and fibrinolysis is unknown. We aimed to investigate effects of two
      doses of daily endurance exercise on biomarkers of the haemostatic balance in
      overweight men. METHODS: Haemostatic variables were investigated in 53 healthy,
      younger (20-40 years), moderately overweight (BMI 25-30 kg/m(2)) men randomly
      assigned to 3 months of strictly controlled endurance exercise at two different
      doses corresponding to an energy expenditure of 600 kcal/day (HIGH), 300 kcal/day
      (MOD), or to maintain their habitual lifestyle (CON). Fasting blood samples were
      collected before and after the intervention and analysed for thrombin generation
      (endogenous thrombin potential, ETP) and concentrations of tissue-type
      plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and
      von Willebrand factor (vWF). RESULTS: We observed significant within-group
      decreases in ETP (MOD 7 %; HIGH 6 %) and in t-PA (MOD 22 %; HIGH 21 %) and PAI-1
      (MOD 16 %; HIGH 32 %) in both training groups, and no changes in the CON group.
      At 3 months, between-group differences were observed for ETP (p = 0.016) and t-PA
      (p = 0.012) due to significantly lower values in MOD and HIGH compared with CON.
      Borderline significant between-group differences were observed for PAI-1 (p =
      0.082). A significant increase was observed in vWF in HIGH, but with no between
      group differences. CONCLUSIONS: Our results demonstrate an effect of 3 months of
      daily endurance exercise on biomarkers of the haemostatic balance in the
      direction of reduced cardiovascular risk, independent of exercise dose.

PMID- 25618793
TI  - Oligomers, protofibrils and amyloid fibrils from recombinant human lysozyme
      (rHL): fibrillation process and cytotoxicity evaluation for ARPE-19 cell line.
AB  - Amyloid-associated diseases, such Alzheimer's, Huntington's, Parkinson's, and
      type II diabetes, are related to protein misfolding and aggregation. Herein, the
      time evolution of scattered light intensity, hydrophobic properties, and
      conformational changes during fibrillation processes of rHL solutions at 55 
      degrees C and pH 2.0 were used to monitor the aggregation process of recombinant
      human lysozyme (rHL). Dynamic light scattering (DLS), thioflavin T (ThT)
      fluorescence, and surface tension (ST) at the air-water interface were used to
      analyze the hydrophobic properties of pre-amyloid aggregates involved in the
      fibrillation process of rHL to find a correlation between the hydrophobic
      character of oligomers, protofibrils and amyloid aggregates with the gain in
      cross-beta-sheet structure, depending on the increase in the incubation periods.
      The ability of the different aggregates of rHL isolated during the fibrillation
      process to be adsorbed at the air-water interface can provide important
      information about the hydrophobic properties of the protein, which can be related
      to changes in the secondary structure of rHL, resulting in cytotoxic or non
      cytotoxic species. Thus, we evaluated the cytotoxic effect of oligomers,
      protofibrils and amyloid fibrils on the cell line ARPE-19 using the MTT reduction
      test. The more cytotoxic protein species arose after a 600-min incubation time,
      suggesting that the hydrophobic character of pre-amyloid fibrils, in addition to
      the high prevalence of the cross-beta-sheet conformation, can become toxic for
      the cell line ARPE-19.

PMID- 25618792
TI  - Blood lipids and colorectal polyps: testing an etiologic hypothesis using
      phenotypic measurements and Mendelian randomization.
AB  - PURPOSE: Studies linking cholesterol levels to the development of colorectal
      neoplasia are inconsistent, and Mendelian randomization has been suggested as a
      way to help avoid problems with confounding and reverse causation. METHODS: We
      genotyped individuals who received a colonoscopy at Group Health (1998-2007) for
      96 of 102 single-nucleotide polymorphisms identified by the Global Lipids
      Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non
      advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free
      controls. All had at least one available pre-colonoscopy lipid measurement from
      electronic records maintained by Group Health. RESULTS: Advanced adenoma cases
      were more likely than controls to have higher pre-colonoscopy zenith low-density
      lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR
      per 20 mg/dL LDL increase: 1.16, 95 % confidence interval, CI 1.03-1.30; per 40
      mg/dL TG increase: 1.09, 1.03-1.16; and per 20 mg/dL TC increase: 1.09, 1.02
      1.18). For these traits, genotype-polyp ORs using weighted allele scores were not
      statistically significant (OR per increase in score scaled to a 20 mg/dL LDL
      increase: 1.17, 0.78-1.75; a 40 mg/dL TG increase: 1.12, 0.91-1.38; a 20 mg/dL TC
      increase: 0.99, 0.71-1.38). CONCLUSIONS: Cholesterol levels may be associated
      with advanced adenomas, but larger studies are warranted to determine whether
      this association can be attributed to genetics.

PMID- 25618794
TI  - Psychometric properties of the Gambling Related Cognitions Scale (GRCS) in young
      Italian gamblers.
AB  - INTRODUCTION: The involvement in gambling activities is increasing among
      adolescents, together with the risk of developing gambling problems. Given the
      important role of erroneous beliefs on adolescent problematic gambling behavior,
      the aim of this study was to investigate the adequacy of the Gambling Related
      Cognitions Scale (GRCS; Raylu & Oei, 2004) to assess gambling-related distortions
      among youth in Italy. METHODS: The scale was administered to 1656 Italian high
      school students (65% males, mean age=16.15 years, SD=1.44), and analyses were
      carried out with respondents who have gambled during the previous year (N=1224).
      RESULTS: The adequacy of the five-factor model was confirmed (both among male and
      female adolescent gamblers), as well as the reliability of the total scale and
      subscales. Evidence for the validity of the GRCS among adolescents was provided
      confirming the relationship between gambling-related cognitions and problem
      gambling found in previous studies. Research on the validity of the scale was
      also extended by investigating the relationship between cognitive distortions
      about gambling and the frequency of engaging in different gambling activities.
      CONCLUSIONS: Our results confirm that the GRCS is an effective multidimensional
      instrument which accurately measures young gamblers' cognitive distortions
      relating to gambling. As such, it can be used as a useful tool in the assessment
      and treatment of juvenile gambling.

PMID- 25618795
TI  - Implicit alcohol-relaxation associations in frequently drinking adolescents with
      high levels of neuroticism.
AB  - INTRODUCTION: Most individuals start drinking during adolescence, a period in
      which automatically activated or implicit cognitive processes play an important
      role in drinking behavior. The aim of this study was to examine personality
      related antecedents of implicit associations between alcohol and positive or
      negative reinforcement motives in adolescents. It was hypothesized that frequent
      alcohol consumption in combination with specific personality traits (neuroticism
      for negative reinforcement and extraversion for positive reinforcement) could
      predict specific implicit alcohol-relaxation and arousal associations. METHODS:
      Participants completed a brief Big Five Questionnaire and alcohol use questions
      at T1. Approximately eight months later (T2), two Brief Implicit Association
      Tests were completed to assess alcohol-relaxation (negative reinforcement, n=222)
      and alcohol-arousal (positive reinforcement, n=248) associations. RESULTS:
      Results indicated that frequently drinking adolescents who scored high on
      neuroticism had the strongest alcohol-relaxation associations eight months later.
      No significant predictors were observed for alcohol-arousal associations.
      CONCLUSIONS: The current study identified precursors of strong implicit alcohol
      relaxation associations (i.e., high levels of neuroticism in combination with
      frequent alcohol consumption) which can inform future prevention and intervention
      studies.

PMID- 25618796
TI  - 18F-fluoromethylcholine or 18F-fluoroethylcholine pet for prostate cancer
      imaging: which is better? A literature revision.
AB  - INTRODUCTION: The present review was conceived for describing the differences in
      biodistribution and diagnostic performance of two types of (18)F-radiolabeled
      choline for positron emission tomography (PET) imaging in prostate cancer (PCa),
      such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC). MATERIALS AND
      METHODS: A collection of published data about two radiopharmaceutical agents was
      made by using PubMed, Web of Knowledge databases and Trip Database, and then a
      critical revision was discussed. RESULTS: FCH was injected in 338 and 1164
      patients, while FEC was injected in 20 and 139 patients, respectively for basal
      staging and re-staging. The diagnostic performances of FCH and FEC for the
      detection of lymph node metastasis before the surgical approach are typically
      around 50% or less and between 0% and 39%, respectively. Conversely, both the
      tracers appear useful for the detection of recurrent PCa in case of increase in
      absolute PSA value or in case of high levels of PSA velocity and PSA doubling
      time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7%
      for FEC). CONCLUSIONS: In according with the available information, FCH appears
      to be a more appropriate radiocompound as compared to FEC, although more
      comparative data are mandatory. A well designed and prospective trial for the
      evaluation of biokinetic data and diagnostic performance of both
      radiopharmaceutical agents seems essential. ADVANCES IN KNOWLEDGE AND IMPLICATION
      FOR PATIENT CARE: FCH seems to be an appropriate radiopharmaceutical agent as
      compared to FEC. Anyway both the radiocompounds are useful in the evaluation of
      recurrent disease in case of a serial increase in PSA value and their performance
      improves when a correct preparation and acquisition protocol is employed.

PMID- 25618797
TI  - Comment to "Comparison between retrograde intrarenal surgery and extracorporeal
      shock wave lithotripsy in the treatment of lower pole kidney stones up to 15 mm.
      Prospective,randomized study".

PMID- 25618798
TI  - The effect of body temperature, melatonin and cortisol on obesity in women: A
      biochemical evaluation?

PMID- 25618799
TI  - Risk factors for decreased bone mineral density in inflammatory bowel disease: A
      cross-sectional study.
AB  - BACKGROUND & AIM: Although inflammatory bowel disease (IBD) patients are at risk
      for metabolic bone disease, studies analyzing this correlation have identified
      various risk factors, including disease phenotype, age, sex and steroid therapy.
      Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD
      patients. This study analyzed risk factors for metabolic bone disease in Japanese
      IBD patients. METHODS: This cross-sectional study assessed 388 patients with IBD
      aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's
      disease (CD). Bone mineral density of the femoral neck, total femur and lumbar
      spine was quantified by dual-energy X-ray absorptiometry. The blood
      concentrations of bone metabolism markers were measured. History of smoking and
      bone fracture, and nutritional intake were assessed using questionnaires.
      RESULTS: Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had
      osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T
      score. Bone mineral density of the lumbar vertebrae was lower in males than in
      females. Multivariate regression analysis showed that risk factors for bone loss
      in UC patients were male sex, low body mass index (BMI), high steroid dose and
      disease location. Risk factors for bone loss in CD patients were male sex and low
      BMI. CONCLUSION: Among Japanese patients with IBD, male sex and low BMI were
      associated with increased risk for metabolic bone disease. In addition, Steroid
      therapy shouldn't be indiscriminate in UC patients. These findings may help
      identify patients at particularly high risk of metabolic bone disease and may
      help implement appropriate therapies in a timely manner and improve long-term
      quality of life.

PMID- 25618801
TI  - College commences clinical consensus statement development.

PMID- 25618800
TI  - Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in
      subjects with metabolic syndrome: A randomized controlled trial and an updated
      meta-analysis.
AB  - BACKGROUND: Oxidative stress and inflammation have been proposed as emerging
      components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols
      with strong antioxidant and anti-inflammatory properties. OBJECTIVE: To study the
      effectiveness of supplementation with a bioavailable curcuminoid preparation on
      measures of oxidative stress and inflammation in patients with MetS. Our
      secondary aim was to perform a meta-analysis of data from all randomized
      controlled trials in order to estimate the effect size of curcuminoids on plasma
      C-reactive protein (CRP) concentrations. METHODS: In this randomized double-blind
      placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII
      diagnostic criteria) were randomly assigned to curcuminoids (n = 59; drop-outs =
      9) or placebo (n = 58; drop-outs = 8) for eight weeks. Curcuminoids were
      administered at a daily dose of 1 g, and were co-supplemented with piperine (10
      mg/day) in order to boost oral bioavailability. Serum activities of superoxide
      dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured
      at baseline and at study end. Regarding the importance of CRP as a risk marker
      and risk factor of cardiovascular disease, a random-effects meta-analysis of
      clinical trials was performed to estimate the overall impact of curcuminoid
      therapy on circulating concentrations of CRP. The robustness of estimated effect
      size was evaluated using leave-one-out sensitivity analysis. RESULTS:
      Supplementation with curcuminoid-piperine combination significantly improved
      serum SOD activities (p < 0.001) and reduced MDA (p < 0.001) and CRP (p < 0.001)
      concentrations compared with placebo. Quantitative data synthesis revealed a
      significant effect of curcuminoids vs. placebo in reducing circulating CRP
      concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval
      [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis.
      CONCLUSIONS: Short-term supplementation with curcuminoid-piperine combination
      significantly improves oxidative and inflammatory status in patients with MetS.
      Curcuminoids could be regarded as natural, safe and effective CRP-lowering
      agents.

PMID- 25618802
TI  - Nonoperative, dynamic treatment of acute achilles tendon rupture: influence of
      early weightbearing on biomechanical properties of the plantar flexor muscle
      tendon complex-a blinded, randomized, controlled trial.
AB  - Acute Achilles tendon rupture alters the biomechanical properties of the plantar
      flexor muscle-tendon complex that can affect functional performance and the risk
      of repeat injury. The purpose of the present study was to compare the
      biomechanical properties of the plantar flexor muscle-tendon complex in patients
      randomized to early weightbearing or non-weightbearing in the nonoperative
      treatment of Achilles tendon rupture. A total of 60 patients were randomized to
      full weightbearing from day 1 of treatment or non-weightbearing for 6 weeks.
      After 6 and 12 months, the peak passive torque at 20 degrees  dorsiflexion, the
      stiffness during slow stretching, and the maximal strength were measured in both
      limbs. The stiffness of the plantar flexor muscle-tendon complex in the terminal
      part of dorsiflexion was significantly increased (p = .024) in the non
      weightbearing group at 12 months. The peak passive torque was significantly lower
      for the affected limb at 6 months (91%; p = .01), and the stiffness was
      significantly lower for the affected limb during the early part of dorsiflexion
      at 6 (67%; p < .001) and 12 (77%; p < .001) months. In conclusion, an increased
      stiffness of the plantar flexor muscle-tendon complex in the terminal part of
      dorsiflexion was found in the non-weightbearing group. The altered stiffness and
      strength in the affected limb could affect the coordination of gait and running.

PMID- 25618803
TI  - Medial malleolar stress fracture in an adolescent athlete.
AB  - A stress fracture of the medial malleolus in adolescent athletes is a rare
      condition with poorly defined outcomes. Proper management requires early
      recognition, with treatment directed toward the athlete's safe return to their
      sport. Failure to assess and manage the fracture properly can result in
      significant complications, including fracture progression, delayed healing,
      nonunion, and chronic pain. We present the case of a medial malleolar stress
      fracture in a 14-year-old football player, who was successfully able to return to
      competition 4 weeks after surgical treatment. We have also provided a review of
      the published data regarding the management of these injuries and recommendations
      for returning athletes to competition. 

PMID- 25618804
TI  - Repair of the acute deltoid ligament complex rupture associated with ankle
      fractures: a multicenter clinical study.
AB  - Controversy exists concerning the need for operative repair of the deltoid
      ligament during management of acute ankle fractures. The purpose of our report
      was to identify the indications for surgical intervention for deltoid ligament
      injury in the setting of ankle fractures. Furthermore, we aimed to elucidate the
      clinical outcomes after deltoid ligament repair in this setting. This was a
      multicenter study, involving 4 clinical institutions. From January 2006 to
      December 2011, 1533 ankle fractures underwent surgical intervention. Of this
      group, 131 deltoid ligament ruptures (8.55%) were identified and repaired
      operatively. Of the 131 patients, 74 were male (56.5%) and 57 were female
      (43.5%), with a mean age of 33.2 (range 16 to 63) years. The outcome measures
      included the clinical examination findings, radiographic findings, American
      Orthopaedic Foot and Ankle Society ankle-hindfoot scores, visual analog scale
      (VAS) scores, and Medical Outcomes Study Short Form 36-item questionnaire scores.
      All incisions healed primarily. A total of 106 patients were followed up for a
      minimum of 12 (range 12 to 72) months, with an average follow-up period of 27
      months. The mean interval to fracture union was 14.5 (range 9 to 16) weeks. The
      mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score at the
      latest follow-up visit was 91.4 (range 83 to 100) points. The mean visual analog
      scale score was 1.2 (range 0 to 6) points. The mean Short Form-36 score was 91.2
      (range 80 to 96) points. Compared with the preoperative scores, all the 3 outcome
      measures had improved significantly postoperatively (p < .05). The postoperative
      stress radiographs did not reveal any ankle instability. None had evidence of
      post-traumatic arthritis of the ankle from the clinical examination and
      radiographs. A reasonable clinical evaluation and surgical repair was executed,
      with an appropriate repair technique chosen according to the site of deltoid
      ligament rupture. The results of the present multicenter study have shown that
      deltoid ligament rupture can be repaired in patients with an unstable medial
      ankle after fracture fixation and prevent ankle stabilization-related
      complications. 

PMID- 25618805
TI  - Irreducible ankle fracture-dislocation due to tibialis anterior subluxation: a
      case report.
AB  - Irreducible ankle fracture-dislocations are rare. Several cases of irreducible
      ankle fracture-dislocation have been reported in published studies secondary to
      the tibialis posterior tendon, deltoid ligament, or extensor digitorum longus
      tendon blocking the reduction. We report a case of irreducible ankle fracture
      dislocation resulting from posteromedial subluxation of the tibialis anterior
      tendon around a medial malleolar fracture fragment. Ultimately, the ankle
      required open reduction of the incarcerated tendon to reduce the joint and
      proceed with internal fixation of the associated fracture. The patient's
      postoperative course was uncomplicated, and the tibialis anterior tendon was
      functioning at 10 months postoperatively, after which he did not return for
      follow-up examinations. To our knowledge, this is the first reported case of the
      tibialis anterior tendon blocking closed reduction of an ankle fracture
      dislocation.

PMID- 25618806
TI  - White papers, position papers, clinical consensus statements, and clinical
      practice guidelines: future directions for ACFAS.

PMID- 25618807
TI  - Multiple choice answers: what to do when you have too many questions.
AB  - Carrying out too many statistical tests in a single study throws results into
      doubt, for reasons statistical and ethical. I discuss why this is the case and
      briefly mention ways to handle the problem. 

PMID- 25618808
TI  - Surgical outcomes after excision of pigmented villonodular synovitis localized to
      the ankle and hindfoot without adjuvant therapy.
AB  - Although a benign disorder, pigmented villonodular synovitis (PVNS) has a high
      rate of recurrence. Because of the high incidence of recurrence and concern about
      destruction of the affected joint, several adjuvant therapies have been promoted
      without a clear standard treatment strategy. We reviewed cases of PVNS affecting
      the ankle and hindfoot joints (ankle and/or subtalar joints) treated with
      surgical resection without adjuvant therapy in an effort to identify the
      incidence of PVNS recurrence after excision without adjuvant therapy. Of the 10
      cases with a mean follow-up duration of 33.2 +/- 19.8 months, 4 (40%) developed a
      recurrence, with a mean interval of 6 (range 3 to 14) months. At the final follow
      up visit, the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot
      score was 86.6 +/- 12. The clinical outcomes of PVNS affecting the ankle and
      hindfoot joints are associated with a relatively high incidence of recurrence,
      and additional clinical investigation comparing the incidence of recurrence in
      patients undergoing excision versus excision with adjuvant therapy is needed for
      us to better understand this condition and provide more informed recommendations
      to our patients. 

PMID- 25618809
TI  - Complications of metatarsal suture techniques for bunion correction: a systematic
      review of the literature.
AB  - To better understand the safety of suture techniques to reduce the
      intermetatarsal angle in patients with hallux valgus deformity, we undertook a
      systematic review of the complications associated with the use of this technique.
      The suture procedures of 197 patients were analyzed for complications. The number
      of complications in the total group (n = 197) at a pooled mean follow-up period
      of 23.2 months was 39 (19.8%) and included 21 fractures (10.7%), 11 cases of
      hardware failure (5.6%), and 7 cases of hallux varus (3.6%). The cohort of
      patients was further categorized by the specific procedure technique. The number
      of complications in the Mini TightRope((r)) group (n = 132) at a pooled mean
      follow-up period of 16.2 months was 33 (25%) and included 18 fractures (13.6%),
      10 cases of hardware failure (7.6%), and 5 cases of hallux varus (3.8%). The
      number of complications in the syndesmosis technique group (n = 65) at a pooled
      mean follow-up period of 56.1 months was 6 (9.2%) and included 3 fractures (5%),
      1 case of hardware failure (1.5%), and 2 cases of hallux varus (3%). From our
      review of the published experience with this technique, a high complication rate
      can be expected.

PMID- 25618810
TI  - Prenatal factors associated with the neonatal line thickness in human deciduous
      incisors.
AB  - The neonatal line (NNL) is used to distinguish developmental events observed in
      enamel which occurred before and after birth. However, there are few studies
      reporting relationship between the characteristics of the NNL and factors
      affecting prenatal conditions. The aim of the study was to determine prenatal
      factors that may influence the NNL thickness in human deciduous teeth. The
      material consisted of longitudinal ground sections of 60 modern human deciduous
      incisors obtained from full-term healthy children with reported birth histories
      and prenatal factors. All teeth were sectioned in the labio-lingual plane using
      diamond blade (Buechler IsoMet 1000). Final specimens were observed using
      scanning electron microscopy at magnifications 320*. For each tooth, linear
      measurements of the NNL thickness were taken on its labial surface at the three
      levels from the cemento-enamel junction. The difference in the neonatal line
      thickness between tooth types and between males and females was statistically
      significant. A multiple regression analyses confirmed influence of two variables
      on the NNL thickness standardised on tooth type and the children's sex (z-score
      values). These variables are the taking of an antispasmodic medicine by the
      mother during pregnancy and the season of the child's birth. These two variables
      together explain nearly 17% of the variability of the NNL. Children of mothers
      taking a spasmolytic medicine during pregnancy were characterised by a thinner
      NNL compared with children whose mothers did not take such medication. Children
      born in summer and spring had a thinner NNL than children born in winter. These
      results indicate that the prenatal environment significantly contributes to the
      thickness of the NNL influencing the pace of reaching the post-delivery
      homeostasis by the newborn's organism.

PMID- 25618811
TI  - Continuous sagittal radiological evaluation of stair-climbing in cruciate
      retaining and posterior-stabilized total knee arthroplasties using image-matching
      techniques.
AB  - In this study, we evaluated the in vivo kinematics of stair-climbing after
      posterior stabilized (PS) and cruciate retaining (CR) total knee arthroplasty
      (TKA) using radiographic-based image-matching techniques. Mid-flexion
      anteroposterior stability was demonstrated in all knees after CR TKA. However,
      paradoxical femoral translation at low flexion angles was seen in both designs.
      The post-cam mechanism did not function after PS TKA. Larger posterior tibial
      slope in PS TKA was linked to forward sliding of the femur at mid-flexion and
      unintended anterior tibial post impingement at knee extension. CR TKA is more
      sagittally stable in mid-flexion during stair climbing and attention must be
      given to minimize posterior tibial slope when using late cam-post engaging PS TKA
      designs. 

PMID- 25618812
TI  - Primary Repair of Iatrogenic Medial Collateral Ligament Injury During TKA: A
      Modified Technique.
AB  - Intraoperative injury to the medial collateral ligament (MCL) is a rare but
      important complication of total knee arthroplasty (TKA). While described
      treatment methods are mainly primary repair and revision with a more constrained
      implant, a few studies have investigated the outcomes of primary repair without
      constrained implants. A retrospective study was performed to evaluate the
      prevalence of iatrogenic injury to the MCL during primary TKA and determine the
      clinical outcomes of MCL repair augmented with synthetic material without the use
      of a constrained device. The incidence of intraoperative tear of the MCL was
      0.43% (15/3432). No patient demonstrated instability during the follow-up period.
      Primary repair of iatrogenic MCL injury without the use of constrained implants
      appears to be a potential alternative that warrants further investigation. 

PMID- 25618813
TI  - Synthesis, DNA binding and photocleavage, and cellular uptake of an alkyl chain
      linked dinuclear ruthenium(II) complex.
AB  - A dinuclear ruthenium(II) complex [(bpy)2Ru(L(1))Ru(bpy)2]Cl4 {bpy=2,2'
      bipyridine, L(1)=1,6-bis(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-9H
      carbazol-9-yl)hexane} was synthesised and characterized. The calf thymus DNA (ct
      DNA) binding properties of the complex were investigated by means of UV-Visible
      absorption and emission spectrophotometric titrations, ethidium bromide
      competitive binding, steady-state emission quenching with ferrocyanide, DNA
      viscosity measurements, and DNA thermal denaturation. The results indicated that
      the complex avidly binds to ct-DNA most probably through a threading bis
      intercalative mode. The complex was also evidenced to act as an efficient DNA
      photocleaver, and an effective luminescent stain for cytoplasmic of HeLa cells
      with low cytotoxicity. 

PMID- 25618814
TI  - Spectroscopy, calorimetry and molecular simulation studies on the interaction of
      catalase with copper ion.
AB  - In this research, the binding mechanism of Cu(2+) to bovine liver catalase (BLC)
      was studied by fluorescence spectroscopy, ultraviolet-visible (UV-vis) absorption
      spectroscopy, circular dichroism (CD) spectroscopy, isothermal titration
      calorimetry (ITC) and molecular docking methods. The cellar experiment was
      firstly carried out to investigate the inhibition effect of catalase. During the
      fluorescence quenching study, after correcting the inner filter effect (IFE), the
      fluorescence of BLC was found to be quenched by Cu(2+). The quenching mechanism
      was determined by fluorescence lifetime measurement, and was confirmed to be the
      dynamic mode. The secondary structure content of BLC was changed by the addition
      of Cu(2+), as revealed by UV-vis absorption and CD spectra, which further induces
      the decrease in BLC activity. Molecular simulation study indicates that Cu(2+) is
      located between two beta-sheets and two random coils of BLC near to the heme
      group, and interacts with His 74 and Ser 113 residues near a hydrophilic area.
      The decrease of alpha-helix and the binding of His 74 are considered to be the
      major reason for the inhibition of BLC activity caused by Cu(2+). The ITC results
      indicate that the binding stoichiometry of Cu(2+) to catalase is 11.4. Moreover,
      the binding of Cu(2+) to BLC destroyed H-bonds, which was confirmed by the CD
      result. 

PMID- 25618815
TI  - Comparing the diel vertical migration of Karlodinium veneficum (dinophyceae) and
      Chattonella subsalsa (Raphidophyceae): PSII photochemistry, circadian control,
      and carbon assimilation.
AB  - Diel vertical migration (DVM) is thought to provide an adaptive advantage to some
      phytoplankton, and may help determine the ecological niche of certain harmful
      algae. Here we separately compared DVM patterns between two species of harmful
      algae isolated from the Delaware Inland Bays, Karlodinium veneficum and
      Chattonella subsalsa, in laboratory columns. We interpreted the DVM patterns of
      each species with Photosystem II (PSII) photochemistry, rates of carbon
      assimilation, and specific growth rates. Each species migrated differently,
      wherein K. veneficum migrated closer to the surface each day with high population
      synchrony, while C. subsalsa migrated near to the surface from the first day of
      measurements with low population synchrony. Both species appeared to downregulate
      PSII in high light at the surface, but by different mechanisms. C. subsalsa grew
      slower than K. veneficum in low light intensities (~bottom of columns), and
      exhibited maximal rates of C-assimilation (Pmax) at surface light intensities,
      suggesting this species may prefer high light, potentially explaining this
      species' rapid surface migration. Contrastingly, K. veneficum showed declines in
      carbon assimilation at surface light intensities, and exhibited a smaller
      reduction in growth at low (bottom) light intensities (compared to C. subsalsa),
      suggesting that this species' step-wise migration was photoacclimative and
      determined daily migration depth. DVM was found to be under circadian control in
      C. subsalsa, but not in K. veneficum. However, there was little evidence for
      circadian regulation of PSII photochemistry in either species. Migration
      conformed to each species' physiology, and the results contribute to our
      understanding each alga's realized environmental niche. 

PMID- 25618816
TI  - Novel cyanine dyes and homodimeric styryl dyes as fluorescent probes for
      assessment of lactic acid bacteria cell viability.
AB  - Innovations in labeling techniques and in the design and synthesis of dye
      structures are closely related to the development of service equipment such as
      light sources and detection methods. Novel styryl homodimers and monomethine
      cyanine dyes were synthesized and their staining abilities for discrimination
      between live and dead lactic acid bacterial cells were investigated. The dyes
      were combined in pairs based on their excitation and emission maxima and the
      capacity to penetrate through cell membranes of viable bacterial cells. The
      absorption maxima in the same region and the large Stocks shifts of the styryl
      derivatives allowed viability analysis to be done with epifluorescent microscope
      with a very basic configuration - one light source about 480nm and one filter for
      the fluorescent emissions. A staining protocol was developed and applied for
      live/dead analysis of Bulgarian yoghurt starters. The live cells quantification
      by the fluorescence dyes coincided well with the results of the much more time
      consuming tests by plate counting. Thus, the proposed dye combinations are
      appropriate for rapid viability estimation in small laboratories that may have
      conventional equipment. 

PMID- 25618817
TI  - Does performance management affect nurses' well-being?
AB  - AIM: This article focuses on employee performance-management practices in the
      healthcare sector. We specifically aim to contribute to a better understanding of
      the impact of employee performance-management practices on affective well-being
      of nurses in hospitals. Theory suggests that the features of employee-performance
      management (planning and evaluation of individual performances) predict affective
      well-being (in this study: job satisfaction and affective commitment). METHODS:
      Performance-management planning and evaluation and affective well-being were
      drawn from a survey of nurses at a Flemish hospital. Separate estimations were
      performed for different aspects of affective well-being. RESULTS: Performance
      planning has a negative effect on job satisfaction of nurses. Both vertical
      alignment and satisfaction with the employee performance-management system
      increase the affective well-being of nurses; however, the impact of vertical
      alignment differs for different aspects of affective well-being (i.e. job
      satisfaction and affective commitment). CONCLUSION: Performance-management
      planning and evaluation of nurses are associated with attitudinal outcomes. The
      results indicate that employee performance-management features have different
      impacts on different aspects of well-being.

PMID- 25618818
TI  - A long-term study of new particle formation in a coastal environment:
      meteorology, gas phase and solar radiation implications.
AB  - New particle formation (NPF) was investigated at a coastal background site in
      Southwest Spain over a four-year period using a Scanning Particle Mobility Sizer
      (SMPS). The goals of the study were to characterise the NPF and to investigate
      their relationship to meteorology, gas phase (O3, SO2, CO and NO2) and solar
      radiation (UVA, UVB and global). A methodology for identifying and classifying
      the NPF was implemented using the wind direction and modal concentrations as
      inputs. NPF events showed a frequency of 24% of the total days analysed. The mean
      duration was 9.2+/-4.2 h. Contrary to previous studies conducted in other
      locations, the NPF frequency reached its maximum during cold seasons for
      approximately 30% of the days. The lowest frequency took place in July with 10%,
      and the seasonal wind pattern was found to be the most important parameter
      influencing the NPF frequency. The mean formation rate was 2.2+/-1.7 cm(-3) s(
      1), with a maximum in the spring and early autumn and a minimum during the summer
      and winter. The mean growth rate was 3.8+/-2.4 nm h(-1) with higher values
      occurring from spring to autumn. The mean and seasonal formation and growth rates
      are in agreement with previous observations from continental sites in the
      Northern Hemisphere. NPF classification of different classes was conducted to
      explore the effect of synoptic and regional-scale patterns on NPF and growth. The
      results show that under a breeze regime, the temperature indirectly affects NPF
      events. Higher temperatures increase the strength of the breeze recirculation,
      favouring gas accumulation and subsequent NPF appearance. Additionally, the role
      of high relative humidity in inhibiting the NPF was evinced during synoptic
      scenarios. The remaining meteorological variables (RH), trace gases (CO and NO),
      solar radiation, PM10 and condensation sink, showed a moderate or high connection
      with both formation and growth rates.

PMID- 25618819
TI  - Do sediment type and test durations affect results of laboratory-based,
      accelerated testing studies of permeable pavement clogging?
AB  - Previous studies have attempted to quantify the clogging processes of Permeable
      Interlocking Concrete Pavers (PICPs) using accelerated testing methods. However,
      the results have been variable. This study investigated the effects that three
      different sediment types (natural and silica), and different simulated rainfall
      intensities, and testing durations had on the observed clogging processes (and
      measured surface infiltration rates) of laboratory-based, accelerated PICP
      testing studies. Results showed that accelerated simulated laboratory testing
      results are highly dependent on the type, and size of sediment used in the
      experiments. For example, when using real stormwater sediment up to 1.18 mm in
      size, the results showed that neither testing duration, nor stormwater
      application rate had any significant effect on PICP clogging. However, the study
      clearly showed that shorter testing durations generally increased clogging and
      reduced the surface infiltration rates of the models when artificial silica
      sediment was used. Longer testing durations also generally increased clogging of
      the models when using fine sediment (<300 MUm). Results from this study will help
      researchers and designers better anticipate when and why PICPs are susceptible to
      clogging, reduce maintenance and extend the useful life of these increasingly
      common stormwater best management practices.

PMID- 25618820
TI  - Ambient air benzene at background sites in China's most developed coastal
      regions: exposure levels, source implications and health risks.
AB  - Benzene is a known human carcinogen causing leukemia, yet ambient air quality
      objectives for benzene are not available in China. The ambient benzene levels at
      four background sites in China's most developed coastal regions were measured
      from March 2012 to February 2013. The sites are: SYNECP, in the Northeast China
      Plain (NECP); YCNCP, in the North China Plain (NCP); THYRD, in the Yangtze River
      Delta (YRD) and DHPRD, in the Pearl River Delta (PRD). It was found that the mean
      annual benzene levels (578-1297 ppt) at the background sites were alarmingly
      higher, especially when compared to those of 60-480 pptv monitored in 28 cities
      in the United States. Wintertime benzene levels were significantly elevated at
      both sites (SYNECP and YCNCP) in northern China due to heating with
      coal/biofuels. Even at these background sites, the lifetime cancer risks of
      benzene (1.7-3.7E-05) all exceeded 1E-06 set by USEPA as acceptable for adults.
      At both sites in northern China, good correlations between benzene and CO or
      chloromethane, together with much lower toluene/benzene (T/B) ratios, suggested
      that benzene was largely related to coal combustion and biomass/biofuel burning.
      At the DHPRD site in the PRD, benzene revealed a highly significant correlation
      with methyl tert-butyl ether (MTBE), indicating that its source was predominantly
      from vehicle emissions. At the THYRD site in the YRD, higher T/B ratios and
      correlations between benzene and tetrachloroethylene, or MTBE, implied that
      benzene levels were probably affected by both traffic-related and industrial
      emissions.

PMID- 25618821
TI  - WITHDRAWN: Correlation of Volume Control Parameters With Health-Related Quality
      of Life in Renal Transplant Patients.

PMID- 25618822
TI  - Co-delivery of doxorubicin and siRNA by a simplified platform with
      oligodeoxynucleotides as a drug carrier.
AB  - The greatest challenge in combining chemotherapy and gene therapy is the
      construction of a suitable platform for the co-delivery of the drug and the
      therapeutic gene. In this study, a simplified and effective system for the co
      loading and intracellular co-delivery of doxorubicin (Dox) and siRNA was
      developed. Oligodeoxynucleotides with CGA repeating units (CGA-ODNs) were
      introduced to load Dox. The loading mechanism was based on the ability of Dox to
      intercalate within double-stranded 5'-GC-3' or 5'-CG-3' sequences.
      Poly(ethyleneimine) (PEI) was used to condense siRNA and Dox loaded CGA-ODNs (CGA
      ODNs-Dox) to obtain Dox and siRNA co-loaded nanocomplexes (PEI/CGA-ODNs
      Dox&siRNA, PDR). The cellular uptake of PDR in A549 and HepG2 cells was 39.52%
      and 36.78%, respectively, indicating that the co-loading and co-delivery effect
      was achieved through the mono-loading method. An in vitro drug release study
      indicated that CMCS-poly(ethylene glycol) (PEG)-NGR (CPN) modified PDR (CPN-PDR)
      displayed a pH-triggered drug release property due to the reversed surface charge
      of CMCS in an acidic environment. Cellular uptake studies also confirmed that the
      disassembly of CPN-PDR was induced by an acidic pH in the extracellular matrix.
      Moreover, lysosomal escape of both Dox and siRNA was observed. Successful
      accumulation of Dox in the cell nucleus and siRNA in the cytoplasm was also
      demonstrated. Consequently, the novel construction of a simplified loading method
      and high co-delivery efficiency was proven to be a promising platform for the co
      delivery of drug and siRNA. 

PMID- 25618823
TI  - Identification of Arabidopsis MYB56 as a novel substrate for CRL3(BPM) E3
      ligases.
AB  - Controlled stability of proteins is a highly efficient mechanism to direct
      diverse processes in living cells. A key regulatory system for protein stability
      is given by the ubiquitin proteasome pathway, which uses E3 ligases to mark
      specific proteins for degradation. In this work, MYB56 is identified as a novel
      target of a CULLIN3 (CUL3)-based E3 ligase. Its stability depends on the presence
      of MATH-BTB/POZ (BPM) proteins, which function as substrate adaptors to the E3
      ligase. Genetic studies have indicated that MYB56 is a negative regulator of
      flowering, while BPMs positively affect this developmental program. The
      interaction between BPMs and MYB56 occurs at the promoter of FLOWERING LOCUS T
      (FT), a key regulator in initiating flowering in Arabidopsis, and results in
      instability of MYB56. Overall the work establishes MYB transcription factors as
      substrates of BPM proteins, and provides novel information on components that
      participate in controlling flowering time in plants. 

PMID- 25618824
TI  - BEACH-domain proteins act together in a cascade to mediate vacuolar protein
      trafficking and disease resistance in Arabidopsis.
AB  - Membrane trafficking to the protein storage vacuole (PSV) is a specialized
      process in seed plants. However, this trafficking mechanism to PSV is poorly
      understood. Here, we show that three types of Beige and Chediak-Higashi (BEACH)
      domain proteins contribute to both vacuolar protein transport and effector
      triggered immunity (ETI). We screened a green fluorescent seed (GFS) library of
      Arabidopsis mutants with defects in vesicle trafficking and isolated two allelic
      mutants gfs3 and gfs12 with a defect in seed protein transport to PSV. The gene
      responsible for the mutant phenotype was found to encode a putative protein
      belonging to group D of BEACH-domain proteins, which possess kinase domains.
      Disruption of other BEACH-encoding loci in the gfs12 mutant showed that BEACH
      homologs acted in a cascading manner for PSV trafficking. The epistatic genetic
      interactions observed among BEACH homologs were also found in the ETI responses
      of the gfs12 and gfs12 bchb-1 mutants, which showed elevated avirulent bacterial
      growth. The GFS12 kinase domain interacted specifically with the pleckstrin
      homology domain of BchC1. These results suggest that a cascade of multiple BEACH
      domain proteins contributes to vacuolar protein transport and plant defense. 

PMID- 25618826
TI  - Developing performance indicators for clinical governance in dimensions of risk
      management and clinical effectiveness.
AB  - OBJECTIVE: This study has been designed and conducted to develop domestic
      indicators for evaluating the performance of clinical governance in dimensions of
      risk management and clinical effectiveness. DESIGN: This study implemented a 5
      stage process including conducting a comprehensive literature review, expert
      panel (~ 1000 h per person per session, 11 experts), semi-structured interviews,
      a 2-round Delphi study (33 experts were in attendance) and a final expert panel
      (8 experts were in attendance). SETTING: East Azerbaijan-Iran Province.
      PARTICIPANTS: Fifty-six specialists and experts in different fields of medical
      sciences. MAIN OUTCOME MEASURES: Importance and applicability of indicators.
      RESULTS: Using a thorough literature review, 361 indicators (129 risk management
      indicators in 4 dimensions and 232 clinical effectiveness indicators in 18
      dimensions) were found. After conducting expert panels and interviews, the number
      of indicators decreased to 168 cases (65 risk management indicators in 4
      dimensions and 103 clinical effectiveness indicators in 12 dimensions). Two
      rounds of Delphi identified four indicators that were omitted. The members of the
      final expert panel agreed on 113 indicators (43 risk management indicators in 4
      dimensions and 70 clinical effectiveness indicators in 11 dimensions).
      CONCLUSION: In this study, indicators for assessing clinical governance in
      domains of risk management and clinical effectiveness were designed that can be
      used by policy-makers and other authorities for improving the quality of services
      and evaluating the performance of clinical governance. Those indicators can be
      used with slight modifications in other countries having healthcare systems
      similar to that of Iran.

PMID- 25618825
TI  - Administration of embryonic stem cell-derived thymic epithelial progenitors
      expressing MOG induces antigen-specific tolerance and ameliorates experimental
      autoimmune encephalomyelitis.
AB  - Tolerance induction, and thus prevention or treatment of autoimmune disease, is
      not only associated with the persistent presence of self-antigen in the thymus,
      but also relies on a functional thymus; however, the thymus undergoes profound
      age-dependent involution. Thymic epithelial cells (TECs) are the major component
      of the thymic microenvironment for T cell development. We have reported that
      mouse embryonic stem cells (mESCs) can be induced in vitro to generate thymic
      epithelial progenitors (TEPs) that further develop into functional TECs in vivo.
      We show here that transplantation of mESC-TEPs expressing self-antigen myelin
      oligodendrocyte glycoprotein (MOG) in mice results in enhanced T cell
      regeneration, long-term expression of MOG in the thymus, prevention of
      experimental autoimmune encephalomyelitis (EAE) development, and remission of
      established EAE. Our findings indicate that transplantation of ESC-TEPs
      expressing disease-causative self-antigen(s) may provide an effective approach
      for the prevention and treatment of autoimmune disease.

PMID- 25618827
TI  - The elevated C-reactive protein level is associated with poor prognosis in
      prostate cancer patients treated with radiotherapy.
AB  - BACKGROUND: C-reactive protein (CRP) is a sensitive marker of inflammation that
      has been linked with prognosis in various solid tumours. In the present study, we
      analysed the prognostic relevance of elevated plasma CRP levels in prostate
      cancer patients treated with radiotherapy. METHODS: A total of 261 prostate
      cancer patients treated with 3D-conformal radiotherapy were evaluated
      retrospectively. Cancer specific survival (CSS), overall survival (OS) and
      clinical disease-free survival (DFS) were assessed using Kaplan-Meier analysis.
      To evaluate the independent prognostic significance of CRP plasma levels,
      multivariate Cox regression models were applied. RESULTS: The median follow-time
      was 80months. Applying receiver operating characteristics (ROC) analysis, the
      optimal cut-off level for the plasma CRP was 8.6mgl(-1). An elevated CRP level
      was associated with decreased CSS in univariate (hazard ratio (HR) 3.36, 95%
      confidence interval (CI) 1.42-7.91; p=0.006) and multivariate analysis (HR 4.31,
      95% CI 1.22-15.1; p=0.023). Furthermore, a significant association with OS was
      detected in univariate (HR 2.69, 95% CI 1.57-4.59; p<0.001) and multivariate
      analyses (HR 3.24, 95% CI 1.84-5.71, p<0.001). Multivariate analysis also showed
      a significant association between plasma CRP and clinical DFS (HR 2.07, 95% CI
      1.02-4.17; p=0.043). CONCLUSIONS: In the present study, an elevated plasma CRP
      (?8.6mgl(-1)) has been identified as a prognostic factor for poor CSS, OS and DFS
      in prostate cancer patients undergoing radiotherapy. The association between
      elevated CRP levels and poor prognosis was independent of other measures of
      prognosis such as tumour stage, Gleason grading and prostate specific antigen
      (PSA) level at diagnosis. If confirmed by additional studies, our findings may
      contribute to future individual risk assessment in prostate cancer patients.

PMID- 25618828
TI  - Phase II study of pazopanib as second-line treatment after sunitinib in patients
      with metastatic renal cell carcinoma: a Southern China Urology Cancer Consortium
      Trial.
AB  - This multicentre, single arm, phase II study was aimed to assess the efficacy and
      safety of pazopanib as second-line treatment after failure of sunitinib in
      patients with metastatic renal cell carcinoma (mRCC) and explore biomarkers for
      pazopanib response. Patients received pazopanib 800mgperday. The primary end
      point was progression-free survival (PFS). Secondary end-points included
      objective response rate (ORR), overall survival (OS) and safety. Serum proteins
      (Delta-like ligand (DLL4), Notch1, hypoxia inducible factor-1alpha (HIF-1alpha),
      HIF-2alpha, vascular endothelial growth factor A (VEGFA) and platelet-derived
      growth factor receptor beta (PDGFRB)) levels were measured using enzyme-linked
      immunosorbent assay (ELISA). 86 patients with clear cell mRCC were enrolled from
      December 2009 to March 2012 from three centres in Southern China. Of 85 evaluable
      patients, the median PFS was 5.6months (95% confidence interval (CI), 4.1
      6.7months) by independent review. No complete response (CR) was observed in all
      patients. 13 (15.3%; 95% confidence interval [CI], 11.2-23.9%) patients achieved
      partial responses (PR) (ORR 15.3%). Median OS was 18.1months (95% CI, 13.2
      19.8months). The most common adverse events (AEs) were mild to moderate and
      clinically manageable, including hypertension (37.6%), diarrhoea (36.5%),
      increased AST (51.8%), and anaemia (60%). AEs resulted in dose reduction in 24.7%
      of patients. Multivariable analysis showed that higher baseline levels of DLL4
      and VEGFA and lower baseline level of HIF-2alpha were associated with shorter
      PFS; only lower baseline level of HIF-2alpha was correlated with shorter OS. The
      lower expression level of DLL4 after pazopanib treatment was associated with
      higher response rate probability. In conclusion, pazopanib was clinically active
      and well tolerated as second-line treatment after sunitinib in mRCC patients.
      Baseline levels of serum DLL4, VEGFA and HIF-2alpha may have potential utility as
      biomarkers of clinical efficacy in this setting (chiCTR-TRC-13004016). 

PMID- 25618829
TI  - Development and validation of fast and simple flow injection analysis-tandem mass
      spectrometry (FIA-MS/MS) for the determination of metformin in dog serum.
AB  - A simple, fast and sensitive quantification method for the drug metformin in dog
      serum was developed using flow injection analysis (FIA)-tandem mass spectrometry
      (MS/MS). The method was fully validated according to industry standards. It is
      the first time that FIA-MS/MS for metformin was developed surpassing all existing
      methods in terms of time of analysis. The quantification method was dependent on
      the formation of [M+H](+) using electrospray ionization (ESI) and employing
      multiple reaction monitoring (MRM) using quadrupole-linear ion trap (4000
      QTRAP((r))) instrument. A deuterated internal standard (IS) of metformin bearing
      six deuterium atoms was used to compensate for matrix effects and for variation
      in ion current within the ESI source. The ion transitions that were monitored
      were m/z 130.1->m/z 71.0 and m/z 130.1->m/z 60.1 for metformin and m/z 136.0->m/z
      77.0 for the internal standard. A linear response (r=0.9966) was established for
      a range of concentrations of 5-2340 ng/mL. The inter- and intra-day variations
      were within the acceptable criteria for all quality control samples. The method
      was successfully applied for measurement of serum metformin concentration in dogs
      after intravenous injection.

PMID- 25618830
TI  - Might extended education decrease inequalities in health?-a meta-analysis.
AB  - BACKGROUND: Health is substantially worse in less educated people, and extended
      education might potentially improve their health. A prerequisite for a beneficial
      health effect of education is that the effect is absolute. An absolute effect of
      education means that the health effect comes about independently of any effect on
      other persons. A relative effect, on the other hand, only contributes to
      individual competitiveness in relation to others. Studies of natural experiments
      of extended compulsory education, and other educational-policy changes, provide
      an option for the analysis of absolute effects of education. Published studies,
      however, present conflicting results. METHODS: A meta-analysis was performed of
      European studies where the health effects of extended compulsory or secondary
      level education on low-educated individuals were investigated. RESULTS: Twenty
      two relevant publications were identified. The meta-analysis indicated
      statistically significant favourable effects of educational reforms on rates of
      mortality, self-reported poor health and obesity. The effects were, however,
      small, 1-4%. CONCLUSIONS: An educational reform that typically added one
      educational year in the least educated group was associated with a mean 2.1%
      reduction in mortality in men before age 40. This effect might be compared with
      the total educational gradients of mortality rates in Swedish men at ages 30-64.
      One extra year of education after compulsory education corresponds to a 41%
      reduction in mortality, which is 20 times more than the absolute effect of
      education found in this meta-analysis. Thus, it unlikely that extended compulsory
      education will substantially improve the health of the least educated
      individuals.

PMID- 25618831
TI  - Biosynthesis and Biotechnology of High-Value p-Menthane Monoterpenes, Including
      Menthol, Carvone, and Limonene.
AB  - Monoterpenes of the p-menthane group are volatile secondary (or specialized)
      metabolites found across the plant kingdom. They are dominant constituents of
      commercially important essential oils obtained from members of the genera Mentha
      (Lamiaceae), Carum (Apiaceae), Citrus (Rutaceae), and Eucalyptus (Myrtaceae). p
      Menthane monoterpenes have also attracted interest as chiral specialty chemicals,
      and the harvest from natural sources is therefore supplemented by chemical
      synthesis. More recently, microbial and plant-based platforms for the high-level
      accumulation of specific target monoterpenes have been developed. In this review
      chapter, I discuss the properties of the genes and enzymes involved in p-menthane
      biosynthesis and provide a critical assessment of biotechnological production
      approaches.

PMID- 25618832
TI  - Agreement between resident and faculty emergency physicians in the application of
      NEXUS criteria for suspected cervical spine injuries.
AB  - BACKGROUND: The National Emergency X-Radiography Utilization Study (NEXUS)
      developed a decision rule for when cervical spine radiographs are required in the
      setting of trauma. To our knowledge, inter-rater reliability between resident and
      faculty emergency physicians has not been studied. OBJECTIVE: This study seeks to
      compare the inter-rater agreement of postgraduate year (PGY) 2-4 emergency
      medicine (EM) residents vs. EM faculty physicians. METHODS: A convenience sample
      of patients presenting to an urban, academic, Level II emergency department (ED)
      with complaints of cervical spine pain after trauma were enrolled. All subjects
      received separate examinations by an EM faculty physician and by a PGY 2-4 EM
      resident in a blinded fashion. Eighty subjects were enrolled in the study.
      RESULTS: Agreement for each of the NEXUS components were: posterior midline
      tenderness (PMT) 85.0% and kappa = 0.70, intoxication (TOX) 95.0% and kappa =
      0.72, altered mental status (AMS) 87.5% and kappa = 0.22, focal neurologic
      deficit (FND) 92.5% and kappa = 0.21, and presence of a distracting injury (DIS)
      88.8% and kappa = 0.13. Overall agreement for need for radiographs was 77.5% and
      kappa = 0.53. Sixty of the subjects received radiography (28 computed tomography,
      40 plain films, 8 both). One fracture (C1 lamina) was detected in this dataset.
      Two of the five NEXUS criteria (PMT, TOX) demonstrated substantial agreement, two
      (AMS, FND) fair agreement, and one (DIS) slight agreement. CONCLUSIONS: Based on
      our findings, there was considerable difference in agreement between staff
      physicians and residents. This could be due to the level of experience of the
      provider or the subjectiveness of components the criteria.

PMID- 25618833
TI  - An uncommon cause of acute back pain: spinal subarachnoid hemorrhage progressing
      to spinal cord compression.
AB  - BACKGROUND: Spinal subarachnoid hemorrhage (SSH) is an uncommon occurrence
      responsible for <1% of all cases of subarachnoid hemorrhage (SAH). CASE REPORT:
      We present the case of a 53-year-old man who presented to the emergency
      department (ED) with acute onset of "tearing" back pain that began during
      activity, and who was diagnosed with an SSH that ultimately progressed to spinal
      cord compression. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although
      uncommon, the consequences of SSH are potentially devastating, yet reversible,
      making awareness of this condition critical. Several rare yet potentially
      devastating causes of acute back pain are deserving of consideration when
      approaching back pain in the ED setting; SSH is among them. Pain that is
      described as "tearing" or that is unresponsive to ordinary analgesic dosages
      should prompt strong consideration of vascular or other serious pathology,
      including arterial dissection or spinal cord compression.

PMID- 25618834
TI  - The contributions of emergency physicians to out-of-hospital cardiopulmonary
      arrest: an analysis of the national Utstein Registry data.
AB  - BACKGROUND: Emergency physicians are likely to play an important role in the
      "chain of survival." The relationship between the number of emergency physicians
      and out-of-hospital cardiopulmonary arrest (OHCA) prognosis is not well
      understood. OBJECTIVE: We assessed the impact of the number of emergency
      physicians on the outcomes of OHCA. METHODS: In a nationwide, population-based,
      observational study, we enrolled 120,721 adults aged >= 18 years with OHCA, from
      January 1, 2010 to December 31, 2010. We used the countrywide Utstein Registry
      database coupled with health statistics data surveyed by the Ministry of Health,
      Labour and Welfare. The primary endpoint was favorable neurological outcomes 1
      month after OHCA. RESULTS: During the study period, OHCA occurred in 25,580
      people (21.2%) in an area with the number of emergency physicians/100,000
      population < 1.5, in 62,299 people (51.6%) in an area with >= 1.5 and < 3.0
      emergency physicians/100,000 population, in 30,948 people (25.6%) in an area with
      >= 3.0 and < 4.5 emergency physicians/100,000 population, and in 1894 people
      (1.6%) in an area with >= 4.5 emergency physicians/100,000 population. Patient
      prognosis became more favorable as the number of emergency physicians increased
      (1-month survival: 5.08% vs. 5.81% vs. 5.90% vs. 8.82%, p < 0.0001; and favorable
      neurological outcomes: 2.64% vs. 2.84% vs. 3.23% vs. 3.54%, p < 0.0001; for
      emergency physicians/100,000 population of < 1.5, >= 1.5 and < 3.0, >= 3.0 and <
      4.5, and >= 4.5, respectively). The adjusted odds ratio for favorable
      neurological outcomes per increase of one emergency physician/100,000 population
      was 1.06 (95% confidence interval 1.01-1.11, p = 0.0163). CONCLUSION: An
      increased number of emergency physicians/100,000 population is likely to be
      associated with improved outcomes.

PMID- 25618835
TI  - Increasing off-service resident productivity while on their emergency department
      rotation using shift cards.
AB  - BACKGROUND: Differences in productivity between off-service residents rotating in
      the emergency department (ED) and their emergency medicine (EM) resident
      counterparts have never been directly quantified. OBJECTIVES: We sought to
      quantify the difference between off-service residents rotating in the ED and
      their EM resident counterparts. We also sought to find whether shift cards could
      be used to increase the productivity of off-service residents rotating in the ED.
      METHODS: This is a prospective cohort study conducted at an urban, tertiary,
      Level I trauma center. We implemented the use of shift cards for off-service
      residents during their EM rotation. Completion of the shift card involved
      recording patients seen and their dispositions, procedures done, and documenting
      a learned bedside teaching point from their shift that day. Productivity was
      measured in terms of patients seen per hour (PPH) and relative value units per
      hour (RVU/h). RESULTS: Off-service residents showed a productivity of 0.529 PPH
      (95% confidence interval [CI] 0.493-0.566) and 1.40 RVU/h (95% CI 1.28-1.53)
      prior to implementation of shift cards. With the introduction of shift cards,
      productivity increased to 0.623 PPH (95% CI 0.584-0.663, p = 0.001) and 1.77
      RVU/h (95% CI 1.64-1.91, p = 0.001). In comparison, first year EM resident
      productivity was 0.970 PPH (95% CI 0.918-1.02) and 3.01 RVU/h (95% CI 2.83-3.19).
      CONCLUSIONS: Shift cards can be used to foster motivation for off-service
      residents rotating in the ED, and is a simple and cost-effective method to
      improve system-based practices and utilization of resources.

PMID- 25618836
TI  - Factors associated with early cessation of breastfeeding in women with
      gestational diabetes mellitus.
AB  - AIM: To determine factors associated with early cessation of breastfeeding (<= 3
      months) in women with recent gestational diabetes mellitus (GDM). METHODS: A
      cross-sectional online survey of women aged >= 18 years, diagnosed with GDM in
      2010 and registered with the National Diabetes Services Scheme in Australia. The
      59 questions examined breastfeeding duration, intention, attitudes, exclusivity
      and support. RESULTS: 738 women completed the survey (15% response rate). Data
      was analysed for 729 eligible respondents. Of these 97% reported 'ever'
      breastfeeding and 19% had breastfed for <= 3 months. Cessation of breastfeeding
      at or before 3 months was associated with breastfeeding problems at home
      [adjusted odds ratio 8.01, 95% confidence interval (4.57, 14.05)], return to work
      prior to three months [OR 3.39 (95% CI 1.53, 7.55)], inadequate breastfeeding
      support [OR 1.88 (95% CI 1.10, 3.22)], caesarean delivery [OR 1.70 (95% CI 1.04,
      2.76)], low socioeconomic status (SEIFA 1 unit increase) [OR 0.89 (95% CI 0.81,
      0.97)] and BMI (2 unit increase) [OR 1.08 (95% CI 1.01, 1.57)]. Being married or
      de facto [OR 0.14 (95% CI 0.03, 0.62)] was a protective against early cessation
      of breastfeeding. CONCLUSION: Strategies to improve breastfeeding duration in
      women with GDM need to address those most at risk of early cessation and provide
      appropriate postpartum breastfeeding support in this group.

PMID- 25618837
TI  - Aboriginal women in rural Australia; a small study of infant feeding behaviour.
AB  - BACKGROUND: Aboriginal women in rural areas have lower rates of breastfeeding
      than Australian averages. The reasons for this are poorly understood. Aboriginal
      people experience higher morbidity and increased rates of chronic disease
      throughout the life cycle. The protective effects of sustained breastfeeding
      could benefit rural Aboriginal communities. OBJECTIVE: To explore the factors
      impacting upon infant feeding choices in a rural Aboriginal Community. METHODS:
      Semi-structured interviews were conducted with eight Aboriginal rural dwelling
      first time mothers. These women received a continuity of midwife and Aboriginal
      Health Worker model of care. Interviews were also undertaken with five Aboriginal
      Health Workers and two Aboriginal community breastfeeding champions. The analysis
      was integrated with a conventional literature review and was further developed
      and illustrated with historical literature. Indigenist methodology guided the
      study design, analysis and the dissemination of results. RESULTS: Three key
      themes were identified. These were "I'm doing the best thing for..." which
      encompasses the motivations underpinning infant feeding decisions; "this is what
      I know..." which explores individual and community knowledge regarding infant
      feeding; and "a safe place to feed" identifying the barriers that negative
      societal messages pose for women as they make infant feeding decisions. It
      appears loss of family and community breastfeeding knowledge resulting from
      colonisation still influences the Aboriginal women of today. DISCUSSION:
      Aboriginal women value and trust knowledge which is passed to them from extended
      family members and women within their Community. Cultural, historical and
      socioeconomic factors all strongly influence the infant feeding decisions of
      individuals in this study. CONCLUSIONS: Efforts to normalise breastfeeding in the
      culture of rural dwelling Aboriginal women and their supporting community appear
      to be necessary and may promote breastfeeding more effectively than optimal
      professional care of individuals can do.

PMID- 25618838
TI  - Tracking nutrient transfer at the human maternofetal interface from 4 weeks to
      term.
AB  - INTRODUCTION: In this study we have tracked glycogen and glycoprotein flux
      associated with nutrient uptake into trophoblast in early deciduochorial and
      later haemochorial placenta. METHODS: alpha-amylase, glycogen synthase and
      glycogen phosphorylase were immunohistochemically localised in 6-14 week and term
      placenta and first trimester decidua. Placentae of 4-18 weeks' gestation and term
      were also stained with 22 biotinylated lectins. RESULTS: Histochemical data were
      consistent with glycogenolysis in decidual gland epithelium and placental cyto-
      and syncytiotrophoblast; alpha-amylase was present in decidual secretions but
      absent in placenta. Glycogen and glycogen synthase were both apparent in villous
      cytotrophoblast cells and columns. Profound changes were observed in placental
      glycosylation during gestation. Syncytial microvilli were richly glycosylated as
      were first trimester vacuoles but, by term, syncytiotrophoblast showed little
      lectin binding except in microvillous and basal membranes. Cytotrophoblast Golgi
      bodies were active in the first trimester; at term the cells were generally more
      glycosylated than syncytiotrophoblast. DISCUSSION: We deduce that decidual cell
      glycogen is broken down for transport into the placenta where the products may be
      reassembled into glycogen or used for metabolic processes. First trimester
      histiotrophe is internalised by syncytiotrophoblast, then broken down in apical
      vacuoles containing lysosomal markers. This process declines after haemotrophic
      nutrition commences. Transition from histiotrophic to haemotrophic nutrition
      involves reduced amounts of uterine secretory derivatives reaching the placenta,
      and reduction in internalisation of glycoprotein by syncytiotrophoblast,
      presumably reflecting the shift to low molecular weight nutrients. Glycogen
      accumulates in cytotrophoblast from early pregnancy and is mobilised for
      utilisation by fetoplacental tissues.

PMID- 25618839
TI  - Integrated metabolomics for abiotic stress responses in plants.
AB  - Plants are considered to biosynthesize specialized (traditionally called
      secondary) metabolites to adapt to environmental stresses such as biotic and
      abiotic stresses. The majority of specialized metabolites induced by abiotic
      stress characteristically exhibit antioxidative activity in vitro, but their
      function in vivo is largely yet to be experimentally confirmed. In this review,
      we highlight recent advances in the identification of the role of abiotic stress
      responsive specialized metabolites with an emphasis on flavonoids. Integrated
      'omics' analysis, centered on metabolomics with a series of plant resources
      differing in their flavonoid accumulation, showed experimentally that flavonoids
      play a major role in antioxidation in vivo. In addition, the results also suggest
      the role of flavonoids in the vacuole. To obtain more in-depth insights, chemical
      and biological challenges need to be addressed for the identification of unknown
      specialized metabolites and their in vivo functions. 

PMID- 25618840
TI  - Intraoperative neurophysiological monitoring for intradural extramedullary
      tumors: why not?
AB  - BACKGROUND: While intraoperative neurophysiological monitoring (IOM) for
      intramedullary tumors has become a standard in neurosurgical practice, IOM for
      intradural extramedullary tumors (IDEMs) is still under debate. The aim of this
      study is to evaluate the role of IOM during surgery for IDEMs. METHODS: From
      March 2008 to March 2013, 68 patients had microsurgery with IOM for IDEMs (31
      schwannomas, 25 meningiomas, 6 ependymomas of the cauda/filum terminalis, 4
      dermoid cysts and 2 other lesions). The IOM included somatosensory evoked
      potentials (SEPs), motor evoked potentials (MEPs), and--in selected cases--D
      waves. Also preoperative and postoperative neurophysiological assessment was
      performed with SEPs and MEPs. All patients were evaluated at admission and at
      follow up (minimum 6 months) with the Modified McCormick Scale (mMCs). RESULTS:
      Three different IOM patterns were observed during surgery: no change in evoked
      potentials (63 cases), transitory evoked potentials change (3 cases) and loss of
      evoked potentials (2 cases). In the first setting surgery was never stopped and a
      radical tumor removal was achieved (no stop surgery group). In 3 cases of
      transitory evoked potentials change, surgery was temporarily halted but the
      tumors were at the end completely removed (stop and go surgery group). In 2 more
      patients the loss of evoked potentials led to an incomplete resection (stop
      surgery group). No patients presented a worsening of the pre-operative clinical
      conditions (at admission 47 patients presented mMCs 1-2 and 21 patients mMCs 3-5,
      while at follow up 62 patients are mMCS 1-2 and 6 patients mMCs 3-5).
      CONCLUSIONS: In our series significant IOM changes occurred in 5 out of 68
      patients with IDEMs (7.35%), and it is conceivable that the modification of the
      surgical strategy - induced by IOM - prevented or mitigated neurological injury
      in these cases. Vice versa, in 63 patients (92.65%) IOM invariably predicted a
      good neurological outcome. Furthermore this technique allowed a safer tumor
      removal in IDEMs placed in difficult locations as cranio-vertebral junction or in
      antero/antero-lateral position (where rotation of spinal cord can be monitored)
      and even in case of tumor adherent to the spinal cord without a clear cleavage
      plane.

PMID- 25618841
TI  - Upper extremity acute compartment syndrome during tissue plasminogen activator
      therapy for pulmonary embolism in a morbidly obese patient.
AB  - INTRODUCTION: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are more
      frequently observed in morbidly obese patients. Tissue plasminogen activator
      (tPA) is a thrombolytic agent which dissolves the thrombus more rapidly than
      conventional heparin therapy and reduces the mortality and morbidity rates
      associated with PE. Compartment syndrome is a well-known and documented
      complication of thrombolytic treatment. In awake, oriented and cooperative
      patients, the diagnosis of compartment syndrome is made based on clinical
      findings including swelling, tautness, irrational and continuous pain, altered
      sensation, and severe pain due to passive stretching. These clinical findings may
      not be able to be adequately assessed in unconscious patients. PRESENTATION OF
      CASE: In this case report, we present compartment syndrome observed, for which
      fasciotomy was performed on the upper right extremity of a 46-year old morbidly
      obese, conscious female patient who was receiving tPA due to a massive pulmonary
      embolism. DISCUSSION: Compartment syndrome had occurred due to the damage caused
      by the repeated unsuccessful catheterisation attempts to the brachial artery and
      the accompanying tPA treatment. Thus, the bleeding that occurred in the volar
      compartment of the forearm and the anterior compartment of the arm led to acute
      compartment syndrome (ACS). After relaxation was brought about in the volar
      compartment of the forearm and the anterior compartment of the arm, the
      circulation in the limb was restored. CONCLUSION: As soon as the diagnosis of
      compartment syndrome is made, an emergency fasciotomy should be performed. Close
      follow-up is required to avoid wound healing problems after the fasciotomy.

PMID- 25618842
TI  - Dynamic UCLA for single tilted implant in an aesthetic region.
AB  - INTRODUCTION: The aim of this paper was to present a rehabilitation of a patient
      with a dynamic universal castable long abutment (UCLA) for a single tilted
      implant in the anterior maxillary area. PRESENTATION OF CASE: A 57-year-old male
      patient attended the dentistry college clinic complaining of a vertical fracture
      of a residual root of the dental element 22. The tooth extraction was indicated
      for the implant installation. Due to the socket buccal wall thickness, the
      implant was installed with an inclination to the palate. It was done in a two
      stage surgical protocol, and an external hexagon implant (3.75*11.5mm) was
      placed. After a six-month healing period to correct the implant position, a
      dynamic UCLA was set in place, rectifying the implant emergence profile at 20
      degrees . The ceramic structure fitting was performed and, after the patient's
      consent, the prosthesis was finalized and installed. DISCUSSION: After a follow
      up period of twenty months, no complications were observed. CONCLUSION: The
      installation of tilted implants with a dynamic UCLA may be a viable option,
      faster and less invasive than bone grafts.

PMID- 25618843
TI  - Extranodal lymphoma originating in the gluteal muscle with adjacent bone
      involvement and mimicking a soft tissue sarcoma.
AB  - INTRODUCTION: Extranodal lymphoma (ENL) in the muscles is a rare manifestation of
      non-Hodgkin lymphoma (NHL). The aim of this case report is to describe and
      evaluate the clinical presentation and important radiologic features of ENL
      affecting the musculoskeletal system. PRESENTATION OF CASE: We present a 52-year
      old female with a 3-week history of left gluteal pain. Computed tomography (CT)
      showed a non-uniformly early enhancing mass in the left gluteal muscle, the tumor
      demonstrating central necrosis and adjacent bone involvement. Fluorine-18
      fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)/CT showed areas
      of increased (18)F-FDG uptake in the left gluteal musculature, pelvic bones, para
      aortic and mediastinal lymph nodes and both lungs. Histopathological examination
      showed a diffuse large B cell lymphoma (DLBCL). After 8 cycles of R-CHOP
      chemotherapy, the mass in the left gluteal muscle has completely disappeared
      DISCUSSION: Although destructive tumor originating in the gluteal muscle with
      adjacent bone involvement is more common in soft tissue sarcoma, lymphoma should
      be regularly included in the differential diagnosis. While CT is a useful
      modality for assessing soft tissue masses, disruption and injury of the
      surrounding tissues, PET/CT fusion is superior for the detection of unexpected
      extranodal sites of disease, or for exclusion of disease in the presence of
      nonspecific extranodal CT findings. CONCLUSION: A rapid growth pattern and
      destructive masses that invade adjacent structures on CT are key findings of
      DLBCL, and (18)F-FDG PET/CT is a useful imaging modality to accurately determine
      the disease stage and disease aggressiveness of NHL.

PMID- 25618844
TI  - Incidence and reasons for hardware removal following operative fixation of distal
      radius fractures.
AB  - PURPOSE: To determine the incidence and reasons for hardware removal after
      operative fixation of distal radius fractures. METHODS: We retrospectively
      reviewed 33 patients who underwent removal of a volar distal radius plate from
      2007 to 2013. We recorded the primary reason for plate removal, patient sex, body
      mass index, AO fracture type, and plate manufacturer. The total number of both
      distal radius plating procedures and implant removals was analyzed. RESULTS: Of
      the 33 patients who underwent implant removal, the most common reasons for
      removal were pain (30%), tenosynovitis (27%), malunion (24%), infection (12%),
      nonunion (6%), and tendon rupture (3%). The most common AO fracture types
      requiring plate removal were A2, C2, and C3 (7 each). A total of 517 distal
      radius fractures received plate fixation at our institution from 2007 to 2009, a
      number that rose to 610 from 2010 to 2012. The number of distal radius plate
      removals over that same time was relatively constant at 17 and 16, respectively.
      CONCLUSIONS: We advise continued review of reasons for implant removal to limit
      future hardware complications related to volar plating of distal radius
      fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25618845
TI  - Macrolides for diffuse panbronchiolitis.
AB  - BACKGROUND: Diffuse panbronchiolitis (DPB) is a chronic airways disease
      predominantly affecting East Asians. Macrolides, a class of antibiotics, have
      been used as the main treatment for DPB, based on evidence from retrospective and
      non-randomised studies. OBJECTIVES: To assess the efficacy and safety of
      macrolides for DPB. SEARCH METHODS: We searched CENTRAL (2014, Issue 6), MEDLINE
      (1966 to July week 1, 2014), EMBASE (1974 to July 2014), Chinese Biomedical
      Literature Database (CBM) (1978 to July 2014), China National Knowledge
      Infrastructure (CNKI) (1974 to July 2014), KoreaMed (1997 to July 2014) and
      Database of Japana Centra Revuo Medicina (1983 to July 2014). SELECTION CRITERIA:
      Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of
      macrolides for DPB. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed study quality and subsequent risk of bias according to The
      Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes
      were five-year survival rate, lung function and clinical response. We used risk
      ratios (RR) for individual trial results in the data analysis and measured all
      outcomes with 95% confidence intervals (CI). MAIN RESULTS: Only one RCT (19
      participants) with significant methodological limitations was included in this
      review. It found that the computerised tomography images of all participants
      treated with a long-term, low-dose macrolide (erythromycin) improved from
      baseline, while the images of 71.4% of participants in the control group (with no
      treatment) worsened and 28.6% remained unchanged. Adverse effects were not
      reported. This review was previously published in 2010 and 2013. For this 2014
      update, we identified no new trials for inclusion or exclusion. AUTHORS'
      CONCLUSIONS: There is little evidence for macrolides in the treatment of DPB. We
      are therefore unable to make any new recommendations. It may be reasonable to use
      low-dose macrolides soon after diagnosis is made and to continue this treatment
      for at least six months, according to current guidelines.

PMID- 25618846
TI  - Structural insight into how the human helicase subunit MCM2 may act as a histone
      chaperone together with ASF1 at the replication fork.
AB  - MCM2 is a subunit of the replicative helicase machinery shown to interact with
      histones H3 and H4 during the replication process through its N-terminal domain.
      During replication, this interaction has been proposed to assist disassembly and
      assembly of nucleosomes on DNA. However, how this interaction participates in
      crosstalk with histone chaperones at the replication fork remains to be
      elucidated. Here, we solved the crystal structure of the ternary complex between
      the histone-binding domain of Mcm2 and the histones H3-H4 at 2.9 A resolution.
      Histones H3 and H4 assemble as a tetramer in the crystal structure, but MCM2
      interacts only with a single molecule of H3-H4. The latter interaction exploits
      binding surfaces that contact either DNA or H2B when H3-H4 dimers are
      incorporated in the nucleosome core particle. Upon binding of the ternary complex
      with the histone chaperone ASF1, the histone tetramer dissociates and both MCM2
      and ASF1 interact simultaneously with the histones forming a 1:1:1:1 heteromeric
      complex. Thermodynamic analysis of the quaternary complex together with
      structural modeling support that ASF1 and MCM2 could form a chaperoning module
      for histones H3 and H4 protecting them from promiscuous interactions. This
      suggests an additional function for MCM2 outside its helicase function as a
      proper histone chaperone connected to the replication pathway. 

PMID- 25618847
TI  - Detecting riboSNitches with RNA folding algorithms: a genome-wide benchmark.
AB  - Ribonucleic acid (RNA) secondary structure prediction continues to be a
      significant challenge, in particular when attempting to model sequences with less
      rigidly defined structures, such as messenger and non-coding RNAs. Crucial to
      interpreting RNA structures as they pertain to individual phenotypes is the
      ability to detect RNAs with large structural disparities caused by a single
      nucleotide variant (SNV) or riboSNitches. A recently published human genome-wide
      parallel analysis of RNA structure (PARS) study identified a large number of
      riboSNitches as well as non-riboSNitches, providing an unprecedented set of RNA
      sequences against which to benchmark structure prediction algorithms. Here we
      evaluate 11 different RNA folding algorithms' riboSNitch prediction performance
      on these data. We find that recent algorithms designed specifically to predict
      the effects of SNVs on RNA structure, in particular remuRNA, RNAsnp and SNPfold,
      perform best on the most rigorously validated subsets of the benchmark data. In
      addition, our benchmark indicates that general structure prediction algorithms
      (e.g. RNAfold and RNAstructure) have overall better performance if base pairing
      probabilities are considered rather than minimum free energy calculations.
      Although overall aggregate algorithmic performance on the full set of
      riboSNitches is relatively low, significant improvement is possible if the
      highest confidence predictions are evaluated independently. 

PMID- 25618848
TI  - Solid-phase cloning for high-throughput assembly of single and multiple DNA
      parts.
AB  - We describe solid-phase cloning (SPC) for high-throughput assembly of expression
      plasmids. Our method allows PCR products to be put directly into a liquid handler
      for capture and purification using paramagnetic streptavidin beads and conversion
      into constructs by subsequent cloning reactions. We present a robust automated
      protocol for restriction enzyme based SPC and its performance for the cloning of
      >60 000 unique human gene fragments into expression vectors. In addition, we
      report on SPC-based single-strand assembly for applications where exact control
      of the sequence between fragments is needed or where multiple inserts are to be
      assembled. In this approach, the solid support allows for head-to-tail assembly
      of DNA fragments based on hybridization and polymerase fill-in. The usefulness of
      head-to-tail SPC was demonstrated by assembly of >150 constructs with up to four
      DNA parts at an average success rate above 80%. We report on several applications
      for SPC and we suggest it to be particularly suitable for high-throughput efforts
      using laboratory workstations. 

PMID- 25618849
TI  - CODEX: a normalization and copy number variation detection method for whole exome
      sequencing.
AB  - High-throughput sequencing of DNA coding regions has become a common way of
      assaying genomic variation in the study of human diseases. Copy number variation
      (CNV) is an important type of genomic variation, but detecting and characterizing
      CNV from exome sequencing is challenging due to the high level of biases and
      artifacts. We propose CODEX, a normalization and CNV calling procedure for whole
      exome sequencing data. The Poisson latent factor model in CODEX includes terms
      that specifically remove biases due to GC content, exon capture and amplification
      efficiency, and latent systemic artifacts. CODEX also includes a Poisson
      likelihood-based recursive segmentation procedure that explicitly models the
      count-based exome sequencing data. CODEX is compared to existing methods on a
      population analysis of HapMap samples from the 1000 Genomes Project, and shown to
      be more accurate on three microarray-based validation data sets. We further
      evaluate performance on 222 neuroblastoma samples with matched normals and focus
      on a well-studied rare somatic CNV within the ATRX gene. We show that the cross
      sample normalization procedure of CODEX removes more noise than normalizing the
      tumor against the matched normal and that the segmentation procedure performs
      well in detecting CNVs with nested structures.

PMID- 25618850
TI  - A basal level of DNA damage and telomere deprotection increases the sensitivity
      of cancer cells to G-quadruplex interactive compounds.
AB  - Here, with the aim of obtaining insight into the intriguing selectivity of G
      quadruplex (G4) ligands toward cancer compared to normal cells, a genetically
      controlled system of progressive transformation in human BJ fibroblasts was
      analyzed. Among the different comparative evaluations, we found a progressive
      increase of DNA damage response (DDR) markers throughout the genome from normal
      toward immortalized and transformed cells. More interestingly, sensitivity to G4
      ligands strongly correlated with the presence of a basal level of DNA damage,
      including at the telomeres, where the chromosome ends were exposed to the DDR
      without concurrent induction of DNA repair activity, as revealed by the lack of
      53BP1 recruitment and telomere aberrations. The link between telomere uncapping
      and the response to G4 stabilization was directly assessed by showing that a
      partial TRF2 depletion, causing a basal level of telomere localized DDR, rendered
      telomerized fibroblasts prone to G4-induced telomere damage and anti
      proliferative defects. Taken together these data strongly indicate that the
      presence of a basal level of telomere-associated DDR is a determinant of
      susceptibility to G4 stabilization. 

PMID- 25618851
TI  - Engineered ribosomal RNA operon copy-number variants of E. coli reveal the
      evolutionary trade-offs shaping rRNA operon number.
AB  - Ribosomal RNA (rrn) operons, characteristically present in several copies in
      bacterial genomes (7 in E. coli), play a central role in cellular physiology. We
      investigated the factors determining the optimal number of rrn operons in E. coli
      by constructing isogenic variants with 5-10 operons. We found that the total RNA
      and protein content, as well as the size of the cells reflected the number of rrn
      operons. While growth parameters showed only minor differences, competition
      experiments revealed a clear pattern: 7-8 copies were optimal under conditions of
      fluctuating, occasionally rich nutrient influx and lower numbers were favored in
      stable, nutrient-limited environments. We found that the advantages of quick
      adjustment to nutrient availability, rapid growth and economic regulation of
      ribosome number all contribute to the selection of the optimal rrn operon number.
      Our results suggest that the wt rrn operon number of E. coli reflects the
      natural, 'feast and famine' life-style of the bacterium, however, different copy
      numbers might be beneficial under different environmental conditions.
      Understanding the impact of the copy number of rrn operons on the fitness of the
      cell is an important step towards the creation of functional and robust genomes,
      the ultimate goal of synthetic biology. 

PMID- 25618852
TI  - Domain organization within the nuclear export factor Mex67:Mtr2 generates an
      extended mRNA binding surface.
AB  - The Mex67:Mtr2 complex is the principal yeast nuclear export factor for bulk mRNA
      and also contributes to ribosomal subunit export. Mex67 is a modular protein
      constructed from four domains (RRM, LRR, NTF2-like and UBA) that have been
      thought to be joined by flexible linkers like beads on a string, with the RRM and
      LRR domains binding RNAs and the NTF2-like and UBA domains binding FG
      nucleoporins to facilitate movement through nuclear pores. Here, we show that the
      NTF2-like domain from Saccharomyces cerevisiae Mex67:Mtr2 also contributes to RNA
      binding. Moreover, the 3.3 A resolution crystal structure of the
      Mex67(DeltaUBA):Mtr2 complex, supplemented with small angle X-ray scattering
      data, indicated that the LRR domain has a defined spatial relationship to the
      Mex67(NTF2L):Mtr2 region. Conversely, the RRM domain and especially the UBA
      domain are more mobile. The conformation assumed by the LRR and NTF2-like domains
      results in clusters of positively-charged residues on each becoming arranged to
      form a continuous interface for binding RNA on the opposite side of the complex
      to the region that interacts with FG-nucleoporins to facilitate passage through
      nuclear pores. 

PMID- 25618853
TI  - Identification of novel Arabidopsis thaliana upstream open reading frames that
      control expression of the main coding sequences in a peptide sequence-dependent
      manner.
AB  - Upstream open reading frames (uORFs) are often found in the 5'-leader regions of
      eukaryotic mRNAs and can negatively modulate the translational efficiency of the
      downstream main ORF. Although the effects of most uORFs are thought to be
      independent of their encoded peptide sequences, certain uORFs control translation
      of the main ORF in a peptide sequence-dependent manner. For genome-wide
      identification of such peptide sequence-dependent regulatory uORFs, exhaustive
      searches for uORFs with conserved amino acid sequences have been conducted using
      bioinformatic analyses. However, whether the conserved uORFs identified by these
      bioinformatic approaches encode regulatory peptides has not been experimentally
      determined. Here we analyzed 16 recently identified Arabidopsis thaliana
      conserved uORFs for the effects of their amino acid sequences on the expression
      of the main ORF using a transient expression assay. We identified five novel
      uORFs that repress main ORF expression in a peptide sequence-dependent manner.
      Mutational analysis revealed that, in four of them, the C-terminal region of the
      uORF-encoded peptide is critical for the repression of main ORF expression.
      Intriguingly, we also identified one exceptional sequence-dependent regulatory
      uORF, in which the stop codon position is not conserved and the C-terminal region
      is not important for the repression of main ORF expression. 

PMID- 25618854
TI  - Function of the N-terminal segment of the RecA-dependent nuclease Ref.
AB  - The bacteriophage P1 Ref (recombination enhancement function) protein is a RecA
      dependent, HNH endonuclease. It can be directed to create targeted double-strand
      breaks within a displacement loop formed by RecA. The 76 amino acid N-terminal
      region of Ref is positively charged (25/76 amino acid residues) and inherently
      unstructured in solution. Our investigation of N-terminal truncation variants
      shows this region is required for DNA binding, contains a Cys involved in
      incidental dimerization and is necessary for efficient Ref-mediated DNA cleavage.
      Specifically, Ref N-terminal truncation variants lacking between 21 and 47 amino
      acids are more effective RecA-mediated targeting nucleases. We propose a more
      refined set of options for the Ref-mediated cleavage mechanism, featuring the N
      terminal region as an anchor for at least one of the DNA strand cleavage events. 

PMID- 25618855
TI  - Serum folate, cobalamin, homocysteine and methylmalonic acid concentrations in
      pigs with acute, chronic or subclinical Lawsonia intracellularis infection.
AB  - Lawsonia intracellularis is the causative agent of porcine proliferative
      enteropathy. The clinical presentation can be acute (i.e. proliferative
      hemorrhagic enteropathy, PHE), chronic (i.e. porcine intestinal adenomatosis,
      PIA) or subclinical. In humans with chronic enteropathies, low serum folate
      (vitamin B(9)) and cobalamin (vitamin B(12)) concentrations have been associated
      with increased serum concentrations of homocysteine and methylmalonic acid (MMA),
      which reflect the availability of both vitamins at the cellular level. The aim of
      this study was to evaluate serum folate, cobalamin, homocysteine and MMA
      concentrations in serum samples from pigs with PHE, PIA or subclinical L.
      intracellularis infection, and in negative controls. Serum folate, cobalamin,
      homocysteine and MMA concentrations differed significantly among pigs in the PHE,
      PIA, subclinical and negative control groups. Serum folate concentrations in the
      PHE and PIA groups were lower than in the subclinical and negative control
      groups, while serum cobalamin concentrations were lower in the PIA group than in
      other groups. Serum concentrations of homocysteine were higher in the PHE, PIA
      and subclinical groups than in the negative control group. Serum concentrations
      of MMA were higher in the subclinical and PIA groups than in the control group.
      These data suggest that pigs infected with L. intracellularis have altered serum
      cobalamin, folate, homocysteine and MMA concentrations.

PMID- 25618856
TI  - Epigenetic mechanisms contribute to enhanced expression of immune response genes
      in the liver of cows after experimentally induced Escherichia coli mastitis.
AB  - Endotoxins, such as lipopolysaccharide (LPS), are released during infection with
      Gram-negative bacteria, which can result in excessive activation of toll-like
      receptor (TLR) signalling. The aim of the present study was to investigate
      whether epigenetic mechanisms are involved in controlling the onset and
      progression of the systemic inflammatory response. Using chromatin accessibility
      by real-time (CHART) PCR to assess livers from cows with experimentally induced
      Escherichia coli mastitis, this study demonstrated that the chromatin at the site
      of the promoters of the genes encoding TLR2, TLR4, lipopolysaccharide binding
      protein (LBP) and haptoglobin (HP) was opened up 24 h after infection,
      accompanied by enhanced mRNA expression by these genes. Such modulation did not
      occur in the same samples for the alphaS1-casein promoter, which served as a
      negative control. Demethylation of the TLR4 promoter accompanied opening up of
      chromatin. These data suggest that modulation of epigenetic factors might offer a
      novel approach to treating adverse systemic reactions elicited in cows with E.
      coli mastitis. 

PMID- 25618857
TI  - [The role of chromogranin-A and its derived peptide, WE-14 in the development of
      type 1 diabetes mellitus].
AB  - Chromogranin-A is a member of the granine protein family. It is produced in
      neuroendocrine cells via secretory granules. Many cleavage proteins are formed
      from chromogranin-A, from which some have well known biological activity, while
      the function of others is not yet fully known. Serum chromogranin-A levels are
      used in neuroendocrine tumour diagnostics. Recent studies showed that one of its
      cleavage protein, WE-14 may also play a role in the development of type 1
      diabetes. WE-14 may function as an autoantigen for T-cells involved in the
      destruction of beta-cells. This mechanism was previously observed only in non
      obese diabetic mice. Novel results show that WE-14 also serves as a target for
      autoreactive cells in newly diagnosed type 1 diabetic patients as well, which
      reaction can be increased with transglutaminase. In this paper the authors
      summarize the recent knowledge about chromogranin-A and its potential role in the
      pathomechanism of type 1 diabetes mellitus.

PMID- 25618858
TI  - [Molecular genetics of familial tumour syndromes of the central nervous system].
AB  - Although most of the central nervous system tumours are sporadic, rarely they are
      associated with familial tumour syndromes. These disorders usually present with
      an autosomal dominant inheritance and neoplasia develops at younger age than in
      sporadic cases. Most of these tumours are bilateral, multiplex or multifocal. The
      causative mutations occur in genes involved in cell cycle regulation, cell
      growth, differentiation and DNA repair. Studying these hereditary cancer
      predisposition syndromes associated with nervous system tumours can facilitate
      the deeper understanding of the molecular background of sporadic tumours and the
      development of novel therapeutic agents. This review is an update on hereditary
      tumour syndromes with nervous system involvement with emphasis on molecular
      genetic characteristics and their clinical implications.

PMID- 25618859
TI  - [Role of antihypertensive drugs in the treatment of migraine].
AB  - The treatment of migraine depends on the frequency, severity and concomitant
      diseases. There are several specific drugs developed for migraine prevention in
      addition to the additive antimigraine effects of some other non-specific drugs.
      The aim of this literature-based review is to summarize the possible antimigraine
      properties of different antihypertensive agents (beta-blockers, calcium channel
      blockers, angiotensin converting enzyme inhibitors, angiotensin receptor
      blockers, etc.) focusing on the possible side effects (avoidance of beta blockers
      in the absence of heart disease, possible antiparkinson effect of calcium channel
      blockers, additive effect of drugs modifying the renin-angiotensin system
      activity, etc.). Current evidence supports the use of angiotensin converting
      enzyme inhibitors (mainly lisinopril) and angiotensin receptor blockers (mainly
      candesartan) for long-term migraine prevention and blood pressure control. Long
      term beta-blocker treatment should be avoided in the absence of ischemic heart
      disease due to possible unfavourable cardiovascular effects.

PMID- 25618860
TI  - [Pneumococcal vaccination in general practice].
AB  - INTRODUCTION: The prevalence of invasive pneumococcal disease, which is depending
      on risk factors and comorbidities, is increasing over the age of 50 years. Most
      developed countries have recommendations but vaccination rates remain low. AIM:
      To assess the general practitioners' daily practice in relation to pneumococcal
      vaccination and analyse the effect of informing the subjects about the importance
      of pneumococcal vaccination on vaccination routine. METHOD: Subjects over 50
      years of age vaccinated against influenza during the 2012/2013 campaign were
      informed about the importance of pneumococcal vaccination and asked to fill in a
      questionnaire. RESULTS: Of the 4000 subjects, 576 asked for a prescription of
      pneumococcal vaccine (16.5% of females and 11.6% of males, OR 1.67 CI 95% 1.37
      2.04, p<0.001) and 310 were vaccinated. The mean age of females and males was
      70.95 and 69.8 years, respectively (OR 1.01; CI 95% 1.00-1.02; p<0.05).
      Information given by physicians resulted in 33,6% prescription rate, while in
      case it was 8% when nurses provided information (OR 6.33; CI 95% 5.23-7.67;
      p<0.001). As an effect of this study the vaccination rate was 6.3 times higher
      than in the previous year campaign (p<0.001). CONCLUSIONS: General practitioners
      are more effective in informing subjects about the importance of vaccination than
      nurses. Campaign can raise the vaccination rate significantly.

PMID- 25618861
TI  - [Laser treatment for retinopathy of prematurity in neonatal intensive care units.
      Premature Eye Rescue Program].
AB  - INTRODUCTION: Retinopathy of prematurity is a leading cause of childhood
      blindness around the world. AIM: The Department of Ophthalmology at the
      Semmelweis University and the Peter Cerny Neonatal Emergency and Ambulance
      Service started an innovative Premature Eye Rescue Program to reduce the non
      essential transport of premature babies suffering from retinopathy of
      prematurity. METHOD: During the first 5 years 186 eyes of 93 premature babies
      were treated at the bedside with stage 3 retinopathy of prematurity in the
      primary hospitals. RESULTS: In this first 5-years period the authors reduced the
      number of transports of premature babies for laser treatment; 93 children avoided
      the unnecessary transport, saving altogether a distance of 21,930 kilometers for
      children, as well as the ambulance service. CONCLUSIONS: The Premature Eye Rescue
      Program offers a good and effective alternative for treatment of retinopathy in
      the primary hospitals. The authors propose the national extension of this
      program.

PMID- 25618863
TI  - bbcontacts: prediction of beta-strand pairing from direct coupling patterns.
AB  - MOTIVATION: It has recently become possible to build reliable de novo models of
      proteins if a multiple sequence alignment (MSA) of at least 1000 homologous
      sequences can be built. Methods of global statistical network analysis can
      explain the observed correlations between columns in the MSA by a small set of
      directly coupled pairs of columns. Strong couplings are indicative of residue
      residue contacts, and from the predicted contacts a structure can be computed.
      Here, we exploit the structural regularity of paired beta-strands that leads to
      characteristic patterns in the noisy matrices of couplings. The beta-beta
      contacts should be detected more reliably than single contacts, reducing the
      required number of sequences in the MSAs. RESULTS: bbcontacts predicts beta-beta
      contacts by detecting these characteristic patterns in the 2D map of coupling
      scores using two hidden Markov models (HMMs), one for parallel and one for
      antiparallel contacts. beta-bulges are modelled as indel states. In contrast to
      existing methods, bbcontacts uses predicted instead of true secondary structure.
      On a standard set of 916 test proteins, 34% of which have MSAs with < 1000
      sequences, bbcontacts achieves 50% precision for contacting beta-beta residue
      pairs at 50% recall using predicted secondary structure and 64% precision at 64%
      recall using true secondary structure, while existing tools achieve around 45%
      precision at 45% recall using true secondary structure. AVAILABILITY AND
      IMPLEMENTATION: bbcontacts is open source software (GNU Affero GPL v3) available
      at https://bitbucket.org/soedinglab/bbcontacts .

PMID- 25618864
TI  - Prediction of potential disease-associated microRNAs based on random walk.
AB  - MOTIVATION: Identifying microRNAs associated with diseases (disease miRNAs) is
      helpful for exploring the pathogenesis of diseases. Because miRNAs fulfill
      function via the regulation of their target genes and because the current number
      of experimentally validated targets is insufficient, some existing methods have
      inferred potential disease miRNAs based on the predicted targets. It is difficult
      for these methods to achieve excellent performance due to the high false-positive
      and false-negative rates for the target prediction results. Alternatively,
      several methods have constructed a network composed of miRNAs based on their
      associated diseases and have exploited the information within the network to
      predict the disease miRNAs. However, these methods have failed to take into
      account the prior information regarding the network nodes and the respective
      local topological structures of the different categories of nodes. Therefore, it
      is essential to develop a method that exploits the more useful information to
      predict reliable disease miRNA candidates. RESULTS: miRNAs with similar functions
      are normally associated with similar diseases and vice versa. Therefore, the
      functional similarity between a pair of miRNAs is calculated based on their
      associated diseases to construct a miRNA network. We present a new prediction
      method based on random walk on the network. For the diseases with some known
      related miRNAs, the network nodes are divided into labeled nodes and unlabeled
      nodes, and the transition matrices are established for the two categories of
      nodes. Furthermore, different categories of nodes have different transition
      weights. In this way, the prior information of nodes can be completely exploited.
      Simultaneously, the various ranges of topologies around the different categories
      of nodes are integrated. In addition, how far the walker can go away from the
      labeled nodes is controlled by restarting the walking. This is helpful for
      relieving the negative effect of noisy data. For the diseases without any known
      related miRNAs, we extend the walking on a miRNA-disease bilayer network. During
      the prediction process, the similarity between diseases, the similarity between
      miRNAs, the known miRNA-disease associations and the topology information of the
      bilayer network are exploited. Moreover, the importance of information from
      different layers of network is considered. Our method achieves superior
      performance for 18 human diseases with AUC values ranging from 0.786 to 0.945.
      Moreover, case studies on breast neoplasms, lung neoplasms, prostatic neoplasms
      and 32 diseases further confirm the ability of our method to discover potential
      disease miRNAs. AVAILABILITY AND IMPLEMENTATION: A web service for the prediction
      and analysis of disease miRNAs is available at http://bioinfolab.stx.hk/midp/.

PMID- 25618865
TI  - Context-specific metabolic network reconstruction of a naphthalene-degrading
      bacterial community guided by metaproteomic data.
AB  - MOTIVATION: With the advent of meta-'omics' data, the use of metabolic networks
      for the functional analysis of microbial communities became possible. However,
      while network-based methods are widely developed for single organisms, their
      application to bacterial communities is currently limited. RESULTS: Herein, we
      provide a novel, context-specific reconstruction procedure based on metaproteomic
      and taxonomic data. Without previous knowledge of a high-quality, genome-scale
      metabolic networks for each different member in a bacterial community, we propose
      a meta-network approach, where the expression levels and taxonomic assignments of
      proteins are used as the most relevant clues for inferring an active set of
      reactions. Our approach was applied to draft the context-specific metabolic
      networks of two different naphthalene-enriched communities derived from an
      anthropogenically influenced, polyaromatic hydrocarbon contaminated soil, with
      (CN2) or without (CN1) bio-stimulation. We were able to capture the overall
      functional differences between the two conditions at the metabolic level and
      predict an important activity for the fluorobenzoate degradation pathway in CN1
      and for geraniol metabolism in CN2. Experimental validation was conducted, and
      good agreement with our computational predictions was observed. We also
      hypothesize different pathway organizations at the organismal level, which is
      relevant to disentangle the role of each member in the communities. The approach
      presented here can be easily transferred to the analysis of genomic,
      transcriptomic and metabolomic data.

PMID- 25618866
TI  - The enigma that is Dupuytren's contracture.

PMID- 25618868
TI  - Commentary on Larson et al. Genetic and environmental influences in Dupuytren's
      disease: a study of 30,330 Danish twin pairs.

PMID- 25618867
TI  - A review of the classification of Dupuytren's disease.
AB  - Although much has been published about the treatment of Dupuytren's disease,
      there is no clear consensus regarding the most effective form of treatment. Part
      of this uncertainty may result from the absence of a universal method of
      assessing this condition. We undertook a review of the literature in order to
      summarize the various methods by which Dupuytren's disease has been measured and
      quantified. We included all articles that offered a classification or assessment
      system for the disease. We excluded articles that dealt solely with surgical
      technique (although inevitably there was some overlap). We conclude that there
      are many methods of assessment, but that none of them is perfect and that further
      work is needed in the field. 

PMID- 25618869
TI  - Commentary on Akarsu et al. Single versus repetitive injection of lignocaine in
      the management of carpal tunnel syndrome--a randomized controlled trial.

PMID- 25618870
TI  - Commentary on Ecker et al. Supraretinacular endoscopic carpal tunnel release:
      surgical technique with prospective case series.

PMID- 25618871
TI  - Involvement of hand surgeons in research on the genetics and pathogenesis of
      congenital upper limb anomalies.

PMID- 25618872
TI  - Ring D. The future of hand surgery. J Hand Surg Eur. 2014, 39: 1016-7.

PMID- 25618873
TI  - Re: Zyluk A, Szlosser Z. The results of carpal tunnel release for carpal tunnel
      syndrome diagnosed on clinical grounds, with or without electrophysiological
      investigations: a randomized study. J Hand Surg Eur. 2013, 38: 44-9.

PMID- 25618874
TI  - Synchronously detected secondary signet ring cell urinary bladder malignancy from
      the stomach masquerading as genitourinary tuberculosis.
AB  - Secondary bladder neoplasms are very rare and represent 1% of all malignant
      bladder tumours. Among secondary bladder tumours, metastasis from the stomach
      accounts for about 4% of cases. These secondary tumours are generally detected
      during follow-up of patients already treated for gastric cancer. We report a case
      of metastatic adenocarcinoma of the urinary bladder from an occult primary poorly
      differentiated signet ring cell type gastric carcinoma masquerading clinically as
      genitourinary tuberculosis. Our case illustrates the importance of obtaining a
      bladder biopsy in suspected chronic inflammatory conditions such as urinary tract
      tuberculosis before starting medical management to avoid the serious consequences
      of missing a bladder malignancy. 

PMID- 25618875
TI  - What to look for on a breast specimen radiograph: lessons learnt.
AB  - Two women underwent stereotactic sampling of mammographically detected lesions
      with insertion of breast biopsy markers. Localisation of the malignant lesions
      was performed using iodine 125 seeds, with bracketing of the edges of the larger
      lesion. The seeds/lesions were located and excised using a gamma probe. Liga
      clips attached to peripheral sutures at the edges of the specimen enabled
      radiographic orientation. Surgeon and radiologist found the specimen radiographs
      difficult to interpret. In one case the surgeon thought the lesion had been
      removed, mistaking the iodine seed for the biopsy marker. The radiologist noted
      absence of the biopsy marker and marginal calcifications but was concerned the
      seed was absent. Widening the window level allowed seed identification, revealing
      a characteristic rectangular radiolucent area in what had been interpreted as a
      Liga clip. Correct interpretation of the findings helped guide lesion removal,
      intraoperative margin re-excision and confirmed (125)I seed retrieval. 

PMID- 25618876
TI  - Unexplained weight loss in an 80-year-old woman.
AB  - An 80-year-old woman presented with long-standing history of weight loss and
      malnutrition, which had caused her to become reliant on the use of a wheelchair.
      Her symptoms were initially attributed to her medical comorbidities, however,
      during admission it became apparent that she had been suffering from depression
      and had gone on to develop an eating disorder. Eating disorders are most common
      in young adults but can affect all age groups, including the elderly population.
      The diagnosis is rarely considered in such patients and easily overlooked,
      especially when in the presence of chronic conditions and cognitive decline. A
      pre-existing psychiatric issue, most often depression, may also be present in
      this age group. There are no current treatment methods targeting patients in this
      population, who may not respond as effectively to the available strategies
      directed at young adults. It is important to always consider an eating disorder
      as a contributor or direct cause of unexplained weight loss in elderly patients. 

PMID- 25618877
TI  - Galactosaemia: an unusual cause of chronic bilirubin encephalopathy.
AB  - Galactosaemia is a disorder of galactose metabolism in which raised levels of
      galactose and galactose-1-phosphate damage various organs. Although galactosaemia
      is a common metabolic liver disease in childhood, it is a rare cause of neonatal
      hyperbilirubinemia requiring intervention. We report an unusual case of neonatal
      galactosaemia that at presentation had features of acute bilirubin encephalopathy
      requiring exchange transfusion and at discharge had features of chronic bilirubin
      encephalopathy. This case report emphasises the need for timely suspicion and
      diagnosis of this disease for prevention of chronic morbidity. 

PMID- 25618878
TI  - Peripapillary astrocytic hamartomas evolve from the optic nerve.
AB  - Astrocytic hamartomas are rare benign tumours. Spectral domain optical coherence
      tomography (SD-OCT) with advanced visualisation (optic disc cube 200*200) was
      performed on a 27-year-old man with peripapillary astrocytic hamartomas in the
      right eye. En face (OCT scan) view (CT scan) of the optic nerve at the level of
      retinal pigment epithelium revealed optic nerve fibres along with three
      associated areas showing optical shadowing corresponding with astrocytic
      hamartomas in continuum. An area of optical shadowing was also observed
      superiorly in the retinal tissue corresponding with another astrocytic hamartoma.
      Astrocytes in diffusely vascularised rat retina have been reported to be
      immigrants from the optic nerve. En face SD-OCT-based in vivo histology for the
      first time provides strong evidence that peripapillary astrocytic hamartomas are
      derived from optic nerve astrocytes. 

PMID- 25618879
TI  - Hyponatraemic encephalopathy: an unusual stroke mimic.
AB  - We present a case of a 74-year-old man who was admitted to our stroke unit with
      symptoms and signs suggestive of a left total anterior circulation stroke.
      Subsequent MRI failed to support this diagnosis and, furthermore, correction of
      an incidental finding of hyponatraemia due to syndrome of inappropriate
      antidiuretic hormone secretion led to a complete recovery of symptoms.
      Investigation and subsequent exclusion of other potential differential diagnoses
      confirmed the diagnosis of hyponatraemia mimicking acute stroke. 

PMID- 25618880
TI  - Systemic inflammatory disease resolution following cosmetic silicone breast
      implant removal.
AB  - A 37-year-old Caucasian woman presented with subacute, symmetrical inflammatory
      arthralgia, which was affecting her work. Apart from fatigue, she had no other
      constitutional symptoms. She had undergone cosmetic bilateral silicone breast
      implant surgery in 2008. Blood tests revealed erythrocyte sedimentation rate 53
      mm/h, weakly positive antinuclear antibodies and IgG cardiolipin antibody, while
      breast ultrasound revealed a ruptured left silicone implant. The working
      diagnosis was systemic inflammatory disease of uncertain origin. She decided to
      have replacement, rather than removal, of her silicone breast implants privately,
      but her symptoms persisted postoperatively with a new erythema multiforme-like
      rash despite treatment with methotrexate and moderate dose prednisolone.
      Following further consultation with a National Health Service breast surgeon, her
      silicone implants were removed. Within 10 weeks of surgery, all immunomodulatory
      treatment was discontinued with complete symptom and inflammatory response
      resolution. This case illustrates that implant silicone can induce clinically
      significant systemic inflammatory disease and implant removal is essential for
      disease resolution.

PMID- 25618881
TI  - Page kidney due to a renal pseudocyst in a setting of pancreatitis.
AB  - Pancreatic pseudocysts are notorious for their extension beyond the normal
      confines of the pancreatic bed due to dissection of the enzymatic pseudocyst
      fluid along fascial planes. Such collections of pancreatic juice may compress the
      kidney. Extension of the pseudocyst into the perirenal space is, however,
      uncommon. We report a case of pseudocyst of pancreas lying in the subcapsular
      plane of the left kidney with a patent communication with the pancreatic duct
      (pancreaticorenal fistula). The compressive effect of the pseudocyst on the
      kidney compromised intrarenal perfusion as evidenced by a faint nephrogram but a
      normal renal artery. This led to renin-angiotensin-aldosterone mediated
      hypertension-the Page kidney phenomenon. Extensive literature search revealed our
      case to be the only one to describe such an occurrence. 

PMID- 25618882
TI  - ECG phasic voltage changes associated with spontaneous pneumothorax in a patient
      with vanishing lung syndrome.
AB  - Alternating or phasic ECG voltage changes are most commonly associated with
      intrinsic myocardial electrophysiological perturbations or mechanical oscillation
      within a pericardial effusion. Rare descriptions of electrical alternation have
      been reported with pneumothorax. We present a case of a 53-year-old woman with
      vanishing lung syndrome who presented with spontaneous left pneumothorax and
      phasic ECG voltage changes that resolved after re-expansion of the lung. 

PMID- 25618883
TI  - Patient self-demonstration of the anterior drawer test in an ACL deficient knee.

PMID- 25618884
TI  - Spinal cysticercosis: an unusual presentation.
AB  - Spinal intramedullary cysticercosis is an uncommon clinical condition that may
      mimic an intramedullary tumour and can lead to irreversible neurological deficits
      if untreated. We report a case of a 35-year-old man who clinically presented as
      Brown-Sequard syndrome, having thoracic cord cysticercosis at T11 level. MRI of
      the spine revealed a well-defined round intramedullary inflammatory lesion with
      scolex and perilesional oedema at D11 level. 

PMID- 25618885
TI  - A unique cause of interosseous membrane calcification.

PMID- 25618886
TI  - Fatal endotracheal tube obstruction due to the ball valve effect.
AB  - In patients suffering from pulmonary haemorrhage, or in patients who recently
      received a tracheostomy, acute occlusion of the endotracheal tube due to a blood
      clot is a rare, but well-known complication. Acute and complete occlusion of the
      tube is easily recognisable. There are various methods of removing the
      obstructive clot, such as using a bronchoscope with forceps, topical
      thrombolysis, saline lavage and suctioning. There are no guidelines concerning
      preventive routine bronchoscopic lavage. When there is a partial obstruction of
      the endotracheal tube, ventilation is possible, although high inspiratory
      pressures are necessary. If the clot functions as a ball valve ventil, raised
      intrathoracic pressure will cause right-sided heart failure or tension
      pneumothorax. It is important to recognise a partially obstructed tube in time
      and remove the obstruction. 

PMID- 25618887
TI  - Tuberous sclerosis complex: multisystem hamartomas.

PMID- 25618888
TI  - Warfarin therapy for atrial fibrillation in haemodialysis patients: mind the
      (evidence) gap.

PMID- 25618889
TI  - Sex differences in injury during top-level international athletics championships:
      surveillance data from 14 championships between 2007 and 2014.
AB  - BACKGROUND: Injury incidence has been reported for international athletics
      championships from 2007 to 2012. However, it is unclear whether male or female
      athletes differ in risk and/or characteristics of injuries. OBJECTIVE: To compare
      the incidences and characteristics of injuries that occurred during international
      athletics championships between female and male athletes. METHODS: The national
      medical team and the local organising committee physicians reported all injuries
      daily on a standardised injury report form during 14 international championships
      from 2007 to 2014. Relative risks (RR) of injury, 95% CI and magnitude thresholds
      were calculated. RESULTS: The rate of injuries per 1000 registered athletes was
      significantly higher in male (110.3+/-6.8) than in female (88.5+/-6.7) athletes
      (RR=1.25; 95% CI 1.13 to 1.37, small effect size). Male athletes incurred
      significantly more injuries in the thigh (RR=1.64; 95% CI 1.32 to 2.05, small),
      lower leg (RR=1.36; 95% CI 1.05 to 1.75, small) and hip/groin injuries (RR=2.26;
      95% CI 1.31 to 3.88, moderate), more muscle strains (RR=1.64; 95% CI 1.33 to
      2.04, small), cramps (RR=1.81; 95% CI 1.35 to 2.43, small), and especially more
      thigh strains (RR=1.66; 95% CI 1.25 to 2.19, small), but fewer stress fractures
      (RR=0.32; 95% CI 0.12 to 0.81, moderate) than female athletes. A higher injury
      risk of male than of female athletes was observed in sprints (RR=1.32; 95% CI
      1.06 to 1.66, small), middle distance runs (RR=1.48; 95% CI 1.06 to 2.06, small),
      race walks (RR=2.55; 95% CI 1.27 to 5.10, moderate) and jumps (RR=2.13; 95% CI
      1.53 to 2.97, moderate). No sex difference was found for cause and severity of
      injury. CONCLUSIONS: Injury risk during international athletics championships
      differed between female and male athletes for location, type and event groups.
      Injury prevention strategies should be sex-specific, regarding the differences in
      injury location and type.

PMID- 25618890
TI  - Cognitive functional approach to manage low back pain in male adolescent rowers:
      a randomised controlled trial.
AB  - BACKGROUND: Low back pain (LBP) is prevalent among adolescent rowers. This study
      evaluated the efficacy of a cognitive functional approach to reduce LBP in this
      population. METHODS: Thirty-six adolescent male rowers reporting LBP
      participated. Nineteen were randomly allocated to the intervention group to
      receive a cognitive functional approach targeting cognitions, movement patterns,
      conditioning and lifestyle factors relevant to each rower for 8 weeks. The active
      control group (n=17) received usual care from their coaches (rowing skills and
      conditioning exercises). The primary outcome of the study was pain intensity as
      measured by the Numeric Pain Rating Scale during a 15 min ergometer trial
      preintervention and postintervention. Disability (Patient Specific Functional
      Scale and Roland Morris Disability Questionnaire) was measured
      preintervention/postintervention and at 12 weeks follow-up. Isometric muscle
      endurance of the back extensors and lower limb muscles, usual sitting posture and
      regional lumbar kinematic data during a 15 min ergometer row were measured
      preintervention/postintervention. RESULTS: Compared with the control group, the
      intervention group reported significantly less pain during ergometer rowing
      (Numeric Pain Rating Scale -2.4, p=0.008) and reduced disability (Patient
      Specific Functional Scale (4.1, p=0.01); Roland Morris Disability Questionnaire (
      1.7, p=0.003)) following the intervention, and at 12 weeks follow-up. They also
      demonstrated greater lower limb muscle endurance (20.9 s, p=0.03) and postured
      their lower lumbar spine in greater extension during static sitting (-9.6 degrees
      , p=0.007). No significant differences were reported in back muscle endurance and
      regional lumbar kinematics during ergometer rowing. CONCLUSION: Cognitive
      functional approach was more effective than usual care in reducing pain and
      disability in adolescent male rowers. CLINICAL TRIAL REGISTRY NUMBER: Australian
      and New Zealand Clinical Trial Registry Number 12609000565246.

PMID- 25618891
TI  - Electrophysiological Evidence for Impaired Control of Motor Output in
      Schizophrenia.
AB  - Previous research has demonstrated pervasive deficits in response-related
      processing in people with schizophrenia (PSZ). The present study used behavioral
      measures and event-related potentials (ERPs) to test the hypothesis that
      schizophrenia involves specific impairment in the ability to exert control over
      response-related processing. Twenty-two PSZ and 22 matched control participants
      completed a choice response task in counterbalanced testing sessions that
      emphasized only accuracy (the unspeeded condition) or emphasized speed and
      accuracy equally (the speeded condition). Control participants successfully
      modulated behavioral and ERP indices of response-related processing under speed
      pressure, as evidenced by faster and less variable reaction times (RTs) and an
      earlier onset and increased amplitude lateralized readiness potential (LRP). By
      contrast, PSZ were unable to improve RT speed or variability or to modulate the
      LRP under speed pressure, despite showing a decrease in accuracy. Notably,
      response-related deficits in PSZ emerged only in the speeded condition;
      behavioral and ERP measures did not differ between groups in the unspeeded
      condition. Together, these results indicate that impairment in the ability to
      exert control over response-related processing may underlie response-related
      deficits in schizophrenia. 

PMID- 25618893
TI  - Ten years of a national law covering smoke-free school grounds: a brief review.

PMID- 25618892
TI  - Regulatory T cells are not a strong predictor of survival for patients with
      glioblastoma.
AB  - BACKGROUND: Regulatory T cells (Tregs) are potentially prognostic indicators in
      patients with glioblastoma. If differences in frequency of Tregs in tumor or
      blood account for substantial variation in patient survival, then reliably
      measuring Tregs may enhance treatment selection and improve outcomes. METHODS: We
      measured Tregs and CD3+ T cells in tumors and blood from 25 patients with newly
      diagnosed glioblastoma. Tumor-infiltrating Tregs and CD3+ T cells, measured by
      quantitative DNA demethylation analysis (epigenetic qPCR) and by
      immunohistochemistry, and peripheral blood Treg proportions measured by flow
      cytometry were correlated with patient survival. Additionally, we analyzed data
      from The Cancer Genome Atlas (TCGA) to correlate the expression of Treg markers
      with patient survival and glioblastoma subtypes. RESULTS: Tregs, as measured in
      tumor tissue and peripheral blood, did not correlate with patient survival.
      Although there was a correlation between tumor-infiltrating Tregs expression by
      epigenetic qPCR and immunohistochemistry, epigenetic qPCR was more sensitive and
      specific. Using data from TCGA, mRNA expression of Forkhead box protein 3 (FoxP3)
      and Helios and FoxP3 methylation level did not predict survival. While the
      classical glioblastoma subtype corresponded to lower expression of Treg markers,
      these markers did not predict survival in any of the glioblastoma subtypes.
      CONCLUSIONS: Although immunosuppression is a hallmark of glioblastoma, Tregs as
      measured in tissue by gene expression, immunohistochemistry, or demethylation and
      Tregs in peripheral blood measured by flow cytometry do not predict survival of
      patients. Quantitative DNA demethylation analysis provides an objective,
      sensitive, and specific way of identifying Tregs and CD3+ T cells in
      glioblastoma.

PMID- 25618894
TI  - The waterpipe: an emerging global epidemic in need of action.

PMID- 25618896
TI  - Force and aspiration analysis of the ADAPT technique in acute ischemic stroke
      treatment.
AB  - INTRODUCTION: The development of new revascularization devices has significantly
      improved recanalization rates and time to reperfusion. A direct aspiration first
      pass (ADAPT) technique for stroke thrombectomy was recently shown to be an
      effective and rapid way to achieve revascularization. The technique focuses on
      engaging and removing a clot without the use of a separator or retriever by
      relying on the force and aspiration generated by the catheter. We sought to
      compare the physical and fluid dynamic properties (force and aspiration) of
      commercially available catheters to determine the most effective catheter for the
      ADAPT technique. METHODS: Benchtop models were employed to compare aspiration for
      each catheter by submersing the catheter into a graduated cylinder and aspirating
      water. The volume of fluid aspirated and flow rates were calculated. Force of
      aspiration at the tip of each catheter was measured using a vacuum pressure gauge
      while the catheter was attached to a standard aspiration pump. Force was then
      calculated. RESULTS: The Penumbra 5MAX ACE catheter had the greatest aspiration
      rate of all the catheters at 245 mL/min. The Penumbra 5 MAX catheter aspirated
      212 mL/min, followed by the Navien 058 and DAC 057 with 198 mL/min and 197
      mL/min, respectively. The Penumbra 5MAX ACE generated the greatest tip force
      (18.25 g) and the 5MAX had the least amount of force (14.77 g). CONCLUSIONS: The
      physical and fluid dynamic properties of currently available catheters suggest
      that the 5MAX ACE is the optimal catheter to use in direct aspiration for stroke
      therapy.

PMID- 25618897
TI  - Simulating nectarine tree transpiration and dynamic water storage from responses
      of leaf conductance to light and sap flow to stem water potential and vapor
      pressure deficit.
AB  - For isohydric trees mid-day water uptake is stable and depends on soil water
      status, reflected in pre-dawn leaf water potential (Psipd) and mid-day stem water
      potential (Psimd), tree hydraulic conductance and a more-or-less constant leaf
      water potential (Psil) for much of the day, maintained by the stomata.
      Stabilization of Psil can be represented by a linear relationship between canopy
      resistance (Rc) and vapor pressure deficit (D), and the slope (BD) is
      proportional to the steady-state water uptake. By analyzing sap flow (SF),
      meteorological and Psimd measurements during a series of wetting and drying (D/W)
      cycles in a nectarine orchard, we found that for the range of Psimd relevant for
      irrigated orchards the slope of the relationship of Rc to D, BD is a linear
      function of Psimd. Rc was simulated using the above relationships, and its
      changes in the morning and evening were simulated using a rectangular hyperbolic
      relationship between leaf conductance and photosynthetic irradiance, fitted to
      leaf-level measurements. The latter was integrated with one-leaf, two-leaf and
      integrative radiation models, and the latter gave the best results. Simulated Rc
      was used in the Penman-Monteith equation to simulate tree transpiration, which
      was validated by comparing with SF from a separate data set. The model gave
      accurate estimates of diurnal and daily total tree transpiration for the range of
      Psimds used in regular and deficit irrigation. Diurnal changes in tree water
      content were determined from the difference between simulated transpiration and
      measured SF. Changes in water content caused a time lag of 90-105 min between
      transpiration and SF for Psimd between -0.8 and -1.55 MPa, and water depletion
      reached 3 l h(-1) before noon. Estimated mean diurnal changes in water content
      were 5.5 l day(-1) tree(-1) at Psimd of -0.9 MPa and increased to 12.5 l day(-1)
      tree(-1) at -1.45 MPa, equivalent to 6.5 and 16.5% of daily tree water use,
      respectively. Sixteen percent of the dynamic water volume was in the leaves.
      Inversion of the model shows that Psimd can be predicted from D and Rc, which may
      have some importance for irrigation management to maintain target values of
      Psimd. That relationship will be explored in future research. 

PMID- 25618898
TI  - Dinitrogen fixation by legume shade trees and direct transfer of fixed N to
      associated cacao in a tropical agroforestry system.
AB  - Natural abundance of (15)N (delta (15)N) was determined in bulk soil,
      rhizospheric soil and vegetation in an organically managed cacao (Theobroma cacao
      L.) plantation with Inga edulis Mart. legume trees (inga) as the principal shade
      for studying the nitrogen (N) cycle in the system. Cacao without contact with
      legumes in an adjacent plantation was used as the reference for N2 fixation and
      direct N transfer calculations. Bulk and rhizospheric soils contained 72 and 20%,
      respectively, of whole- system N. No vegetation effect on delta (15)N in
      rhizospheric soil was detected, probably due to the high native soil N pool. Fine
      roots of the cacaos associated with inga contained ~35% of N fixed from the
      atmosphere (Nf) out of the total N. Leaves of all species had significantly
      higher delta (15)N than fine roots. Twenty percent of system Nf was found in
      cacao suggesting direct N transfer from inga via a common mycelial network of
      mycorrhizal fungi or recycling of N-rich root exudates of inga. Inga had
      accumulated 98 kg [Nf] ha(-1) during the 14-year history of the plantation. The
      conservative estimate of current N2 fixation rate was 41 kg [Nf] ha(-1) year(-1)
      based on inga biomass only and 50 kg [Nf] ha(-1) year(-1) based on inga and
      associated trees. 

PMID- 25618895
TI  - The allure of the waterpipe: a narrative review of factors affecting the epidemic
      rise in waterpipe smoking among young persons globally.
AB  - OBJECTIVE: The objective of this narrative review is to highlight the
      determinants of the epidemic rise in waterpipe tobacco smoking (WTS) among youth
      globally. The Ecological Model of Health Promotion (EMHP) was the guiding
      framework for the review. DATA SOURCES: The following electronic databases were
      searched: Cochrane library, MEDLINE, EMBASE, PsycINFO, Web of Science and CINAHL
      Plus with Full Text. Search terms included waterpipe and its many variant terms.
      STUDY SELECTION: Articles were included if they were published between 1990 and
      2014, were in English, were available in full text and included the age group 10
      29 years. DATA EXTRACTION: Articles which analysed determinants of WTS at any of
      the levels of the EMHP were retained regardless of methodological rigour: 131
      articles are included. Articles were coded in a standard template that abstracted
      methods as well as results. DATA SYNTHESIS: The review found that methodologies
      used to assess determinants of WTS among youth were often conventional and lacked
      rigor: 3/4 of the studies were cross-sectional surveys and most enrolled non
      representative samples. Within the framework, the review identified determinants
      of WTS at the intrapersonal, interpersonal, organisational, community and policy
      levels. CONCLUSIONS: The review suggests potential interventions to control WTS
      among youth, with emphasis on creative utilisation of social media, and tobacco
      control policies that include the specificities of WTS. The review further
      suggests the need for rigorous qualitative work to better contextualise
      determinants, and prospective observational and experimental studies that track
      and manipulate them to assess their viability as intervention targets.

PMID- 25618899
TI  - Relationship between surgical oncologic outcomes and publically reported hospital
      quality and satisfaction measures.
AB  - BACKGROUND: Hospital-level measures of patient satisfaction and quality are now
      reported publically by the Centers for Medicare and Medicaid Services. There are
      limited metrics specific to cancer patients. We examined whether publically
      reported hospital satisfaction and quality data were associated with surgical
      oncologic outcomes. METHODS: The Nationwide Inpatient Sample was utilized to
      identify patients with solid tumors who underwent surgical resection in 2009 and
      2010. The hospitals were linked to Hospital Compare, which collects data on
      patient satisfaction, perioperative quality, and 30-day mortality for medical
      conditions (pneumonia, myocardial infarction [MI], and congestive heart failure
      [CHF]). The risk-adjusted hospital-level rates of morbidity and mortality were
      calculated for each hospital and the means compared between the highest and
      lowest performing hospital quartiles and reported as absolute reduction in risk
      (ARR), the difference in risk of the outcome between the two groups. All
      statistical tests were two-sided. RESULTS: A total of 63197 patients treated at
      448 hospitals were identified. For patients at high vs low performing hospitals
      based on Hospital Consumer Assessment of Healthcare Providers and Systems scores,
      the ARR in perioperative morbidity was 3.1% (95% confidence interval [CI] = 0.4%
      to 5.7%, P = .02). Similarly, the ARR for mortality based on the same measure was
      -0.4% (95% CI = -1.5% to 0.6%, P = .40). High performance on perioperative
      quality measures resulted in an ARR of 0% to 2.2% for perioperative morbidity (P
      > .05 for all). Similarly, there was no statistically significant association
      between hospital-level mortality rates for MI (ARR = 0.7%, 95% CI = -1.0% to
      2.5%), heart failure (ARR = 1.0%, 95% CI = -0.6% to 2.7%), or pneumonia (ARR =
      1.6%, 95% CI = -0.3% to 3.5%) and complications for oncologic surgery patients.
      CONCLUSION: Currently available measures of patient satisfaction and quality are
      poor predictors of outcomes for cancer patients undergoing surgery. Specific
      metrics for long-term oncologic outcomes and quality are needed.

PMID- 25618901
TI  - Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of
      prospective observational studies.
AB  - BACKGROUND: Adiposity, measured by body mass index, is implicated in
      carcinogenesis. While adult weight gain has diverse advantages over body mass
      index in measuring adiposity, systematic reviews on adult weight gain in relation
      to adiposity-related cancers are lacking. METHODS: PubMed and Embase were
      searched through September 2014 for prospective observational studies
      investigating the relationship between adult weight gain and the risk of 10
      adiposity-related cancers. Dose-response meta-analyses were performed using a
      random-effects model to estimate summary relative risk (RR) and 95% confidence
      interval (CI) for each cancer type. All statistical tests were two-sided.
      RESULTS: A total of 50 studies were included. For each 5kg increase in adult
      weight gain, the summary relative risk was 1.11 (95% CI = 1.08 to 1.13) for
      postmenopausal breast cancer among no- or low-hormone replacement therapy (HRT)
      users, 1.39 (95% CI = 1.29 to 1.49) and 1.09 (95% CI = 1.02 to 1.16) for
      postmenopausal endometrial cancer among HRT nonusers and users, respectively,
      1.13 (95% CI = 1.03 to 1.23) for postmenopausal ovarian cancer among no or low
      HRT users, 1.09 (95% CI = 1.04 to 1.13) for colon cancer in men. The relative
      risk of kidney cancer comparing highest and lowest level of adult weight gain was
      1.42 (95% CI = 1.11 to 1.81). Adult weight gain was unrelated to cancers of the
      breast (premenopausal women, postmenopausal HRT users), prostate, colon (women),
      pancreas, and thyroid. An increase in risk associated with adult weight gain for
      breast cancer was statistically significantly greater among postmenopausal women
      (P heterogeneity = .001) and HRT nonusers (P heterogeneity = .001); that for
      endometrial cancer was alike among HRT nonusers (P heterogeneity = .04).
      CONCLUSIONS: Avoiding adult weight gain itself may confer protection against
      certain types of cancers, particularly among HRT nonusers.

PMID- 25618900
TI  - Adjuvant therapy in lymph node-positive vulvar cancer: the AGO-CaRE-1 study.
AB  - BACKGROUND: Women with node-positive vulvar cancer have a high risk for disease
      recurrence. Indication criteria for adjuvant radiotherapy are controversial. This
      study was designed to further understand the role of adjuvant therapy in node
      positive disease. METHODS: Patients with primary squamous-cell vulvar cancer
      treated at 29 gynecologic cancer centers in Germany from 1998 through 2008 were
      included in this retrospective exploratory multicenter cohort study. Of 1618
      documented patients, 1249 had surgical groin staging and known lymph node status
      and were further analyzed. All statistical tests were two-sided. RESULTS: Four
      hundred forty-seven of 1249 patients (35.8%) had lymph node metastases (N+). The
      majority of N+ patients had one (172 [38.5%]) or two (102 [22.8%]) positive
      nodes. The three-year progression-free survival (PFS) rate of N+ patients was
      35.2%, and the overall survival (OS) rate 56.2% compared with 75.2% and 90.2% in
      node-negative patients (N-). Two hundred forty-four (54.6%) N+ patients had
      adjuvant therapy, of which 183 (40.9%) had radiotherapy directed at the groins
      (+/-other fields). Three-year PFS and OS rates in these patients were better
      compared with N+ patients without adjuvant treatment (PFS: 39.6% vs 25.9%, hazard
      ratio [HR] = 0.67, 95% confidence interval [CI[= 0.51 to 0.88, P = .004; OS:
      57.7% vs 51.4%, HR = 0.79, 95% CI = 0.56 to 1.11, P = .17). This effect was
      statistically significant in multivariable analysis adjusted for age, Eastern
      Cooperative Oncology Group, Union internationale contre le cancer stage, grade,
      invasion depth, and number of positive nodes (PFS: HR = 0.58, 95% CI = 0.43 to
      0.78, P < .001; OS: HR = 0.63, 95% CI = 0.43 to 0.91, P = .01). CONCLUSION: This
      large multicenter study in vulvar cancer observed that adjuvant radiotherapy was
      associated with improved prognosis in node-positive patients and will hopefully
      help to overcome concerns regarding adjuvant treatment. However, outcome after
      adjuvant radiotherapy remains poor compared with node-negative patients. Adjuvant
      chemoradiation could be a possible strategy to improve therapy because it is
      superior to radiotherapy alone in other squamous cell carcinomas.

PMID- 25618902
TI  - Patient satisfaction, outcomes, and the need for cancer-specific quality metrics.

PMID- 25618903
TI  - Validation of biomarkers in subcortical ischaemic vascular disease of the
      Binswanger type: approach to targeted treatment trials.
AB  - OBJECTIVES: Vascular cognitive impairment (VCI) is a heterogeneous group of
      cerebrovascular diseases secondary to large and small vessel disease. We
      hypothesised that biomarkers obtained early in the disease could identify a
      homogeneous subpopulation with small vessel disease. METHODS: We obtained disease
      markers in 62 patients with VCI that included neurological findings,
      neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of
      albumin ratio, matrix metalloproteinases (MMPs), amyloid-beta1-42 and
      phosphorylated-tau181. Proton MR spectroscopic imaging showed ischaemic white
      matter and permeability of the blood-brain barrier (BBB) was measured with
      dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score
      (BDS) with subjective and objective disease markers. In addition, an objective
      set of biomarkers was used for an exploratory factor analysis (EFA) to select
      patients with BD. Patients were followed for an average of 2 years to obtain
      clinical consensus diagnoses. RESULTS: An initial BDS of 6 or greater was
      significantly correlated with a final diagnosis of BD (p<0.05; area under the
      curve (AUC)=0.79). EFA reduced nine objective biomarkers to four factors. The
      most predictive of BD was the factor containing the inflammatory biomarkers of
      increased BBB permeability, elevated albumin index and reduced MMP-2 index
      (factor 2; AUC=0.78). Both measures independently predicted a diagnosis of BD,
      and combining them improved the diagnostic accuracy. CONCLUSIONS: Biomarkers
      predicted the diagnosis of the BD type of subcortical ischaemic vascular disease.
      Using pathophysiological biomarkers to select homogeneous groups of patients
      needs to be tested in targeted treatment trials.

PMID- 25618905
TI  - Primary care practice transformation: start with roles and relationships.

PMID- 25618904
TI  - Psychiatric diagnoses underlying the phenocopy syndrome of behavioural variant
      frontotemporal dementia.
AB  - INTRODUCTION: The frontotemporal dementia (FTD) consortium criteria (2011)
      emphasise the importance of distinguishing possible and probable behavioural
      variant FTD (bvFTD). A significant number of possible patients with bvFTD do not
      show functional decline and remain with normal neuroimaging over time, thus
      exhibiting the bvFTD phenocopy syndrome. A neurodegenerative nature is unlikely
      but an alternative explanation is missing. Our aim was to detect psychiatric
      conditions underlying the bvFTD phenocopy syndrome after extensive evaluation.
      METHODS: We included patients with the bvFTD phenocopy syndrome whereby patients
      with probable bvFTD served as a control group. Patients had to have undergone
      both neurological and psychiatric evaluation. Their charts were reviewed
      retrospectively. Using both qualitative and quantitative methods, psychiatric and
      psychological conditions associated with the clinical syndrome were determined in
      both groups and their relative frequencies were compared. RESULTS: Of 181
      suspected bvFTD cases, 33 patients with bvFTD phenocopy syndrome and 19 with
      probable bvFTD were included. Recent life events, relationship problems and
      cluster C personality traits were the most prevalent psychiatric/psychological
      conditions. The frequency of these conditions was higher in the group of patients
      with the bvFTD phenocopy syndrome (n=28) compared to the probable bvFTD group
      (n=9) (chi(2) p<0.05). CONCLUSIONS: This is the first study thoroughly exploring
      psychiatric causes of the bvFTD phenocopy syndrome, revealing that in most cases
      multiple factors played a contributory role. Our study gives arguments for
      neurological and psychiatric collaboration when diagnosing bvFTD. Prompt
      diagnosis of treatable psychiatric conditions is to be gained.

PMID- 25618906
TI  - Differential obesity indices identify the metabolic syndrome in Black men and
      women in Cape Town: the CRIBSA study.
AB  - AIMS: To determine the obesity indices, specifically waist circumference (WC),
      that identified >=2 other metabolic syndrome (MS) components (2009 criteria) in
      25- to 74-year-old Africans in Cape Town. METHODS: Data were collected from a
      cross-sectional sample by administered questionnaires, clinical measurements and
      biochemical analyses. The obesity cut points were estimated by the Youden Index.
      Logistic regression analyses determined whether obesity cut points identifying
      >=2 MS components occurred at true inflection points. RESULTS: Among the 1099
      participants, the calculated cut points and 95% confidence intervals (CI) were:
      men, WC 83.9 cm (81.6-86.2), waist-to-hip ratio (WHR) 0.89 (0.87-0.90), waist-to
      height ratio (WHtR) 0.50 (0.48-0.52) and body mass index (BMI) 24.1 kg/m(2) (22.0
      26.1); women, WC 94.0 cm (92.6-95.3), WHR 0.85 (0.83-0.87), WHtR 0.59 (0.57-0.60)
      and BMI 32.1 kg/m(2) (29.7-34.6). Raised WC was significantly associated with >=2
      MS components in men: WC 84.0-93.9 cm (odds ratio (OR): 3.19, 95% confidence
      interval (CI): 1.73-5.85) and WC >=94.0 cm (OR: 8.50, 95% CI: 4.44-16.25)
      compared with WC <84.0 cm, and in women: WC 80.0-93.9 cm (OR: 2.93, 95% CI: 1.32
      6.54) and WC >=94.0 cm (OR: 5.33, 95% CI: 2.40-11.85) compared with WC <80.0 cm.
      In the logistic model with BMI for women, obesity (OR: 3.60, 95% CI: 1.82-7.10)
      but not overweight (P = 0.063) was significantly associated with >=2 MS
      components. CONCLUSIONS: Obesity cut points for Africans should be re-evaluated
      and adjusted accordingly.

PMID- 25618907
TI  - Do we need to think beyond BMI for estimating population-level health risks?

PMID- 25618909
TI  - Professor Dr. Sergiu Duca -- a pathbreaker.

PMID- 25618908
TI  - Deep endometriosis infiltrating the recto-sigmoid: critical factors to consider
      before management.
AB  - BACKGROUND: Deep endometriosis invading the bowel constitutes a major challenge
      for the gynecologist. In addition to the greater impact on pain, the high
      incidence of surgical morbidity involved with bowel endometriosis poses a
      therapeutic dilemma for the surgeon. Intestinal involvement by deep endometriotic
      nodules has been estimated to occur in 8-12% of women with endometriosis.
      Individual and clinical factors, pre-operative morphologic characteristics from
      imaging, surgical considerations and impact on quality of life are critical
      variables that should be considered in determining the best therapeutic strategy
      for a patient with deep endometriosis involving the sigmoid and/or the rectum.
      Pre-operative planning is fundamental for defining the optimal therapeutic
      strategy; patient counseling of treatment options, and when surgery is indicated,
      involvement of a multidisciplinary surgical team is required. METHODS: The PubMed
      and Cochrane database were searched for all original and review articles
      published in English, French and Italian, until June 2014. Search terms included
      'deep endometriosis', 'surgical and clinical approach', 'bowel disease', 'quality
      of life', 'management of deep endometriosis'. Special attention was paid to
      articles comparing features of discoid and segmental resection. RESULTS: The
      rationale for the best therapeutic options for patients with deep endometriosis
      has been shown and an evidence-based treatment algorithm for determining when and
      which surgical intervention may be required is proposed. In deciding the best
      treatment option for patients with deep endometriosis involving the sigmoid and
      rectum, it is important to understand how the different clinical factors and pre
      operative morphologic imaging affect the algorithm. Surgery is not indicated in
      all patients with deep endometriosis, but, when surgery is chosen, a complete
      resection by the most appropriate surgical team is required in order to achieve
      the best patient outcome. CONCLUSION: In women with deep endometriosis, surgery
      is the therapy of choice for symptomatic patients when deep lesions do not
      improve with a medical treatment.

PMID- 25618911
TI  - Saturated fat vs. sugar.  A British scientist says sugar's the culprit, not fat,
      and the Mediterranean diet may be the antidote.

PMID- 25618910
TI  - Global Advisory Committee  on Vaccine Safety,  3-4 December 2014.

PMID- 25618912
TI  - New improved CDC Ebola guidance.

PMID- 25618913
TI  - [Surgery of aortic aneurysm of the distal arch combined with CABG under left
      thoracotomy using retrograde cerebral perfusion].

PMID- 25618914
TI  - [Imaging diagnosis Q & A. Infectious endocarditis of the mitral valve, cerebral
      aneurysm and multiple infarction (brain, bilateral kidneys and fundus oculi)].

PMID- 25618915
TI  - Rising oceans, climate change, food aid, and human rights in the Marshall
      Islands.
AB  - Climate change impacts are expected to produce more frequent, longer and
      unpredictable drought periods with further saltwater intrusion in the Marshall
      Islands. As a result, a significant return to traditional food cropping is
      unlikely. This will lead to an increased dependence on food aid, especially in
      the outer atoll populations. An examination of the nutritional content of food
      aid suggests it is likely to lead to poor health outcomes. Dependence on food aid
      has gradually increased over the past 70 years in the Marshall Islands, starting
      with population relocation because of war and nuclear testing and most recently
      because of climate change. The authors argue that the health impacts of the
      supplemental imported diet, combined with migration to population centers, may
      result in an even greater prevalence of chronic diseases, and exert pressures
      that lead to more communicable disease, further exacerbating the syndemics in the
      Marshall Islands. The authors conclude that food aid donors and the Republic of
      the Marshall Islands (RMI) government have human rights obligations to ensure
      that the people in the Marshall Islands have access to adequate nutrition.
      Accordingly, donors and the government should re-examine the content of food and
      ensure it is of sufficient quality to meet the right to health obligations.

PMID- 25618916
TI  - [Clamshell section].

PMID- 25618917
TI  - [Innovation in extending a surgical field in the superior mediastinum during
      surgery of esophageal cancer under thoracoscopy while the patient in a prone
      position].

PMID- 25618918
TI  - [Imaging diagnosis Q & A. Symptomatic mitral valve insufficiency].

PMID- 25618919
TI  - JFHC goes digital.

PMID- 25618920
TI  - Fight flu on all fronts, say nursing leads.

PMID- 25618921
TI  - Troubled families need co-ordinated early help.

PMID- 25618922
TI  - National audit shows care for diabetic mothers is poor.

PMID- 25618923
TI  - Inadequate post-natal care under the spotlight.

PMID- 25618924
TI  - A new era for nursing?

PMID- 25618925
TI  - Supporting teenage mothers through the FNP programme: Part 1.

PMID- 25618926
TI  - Good breakfast habits start early.

PMID- 25618927
TI  - Can we improve our brain health?

PMID- 25618928
TI  - Pre-conceptual care for women with pre-existing diabetes.

PMID- 25618929
TI  - Navigating the learning disability landscape.

PMID- 25618931
TI  - Clarifying nursing titles.

PMID- 25618930
TI  - Nursing voice lacking in euthanasia debate.

PMID- 25618932
TI  - Improving mental health care.

PMID- 25618933
TI  - Paediatric nurses needed.

PMID- 25618934
TI  - Tribute to nursing 'Mumz'.

PMID- 25618935
TI  - The President comments.

PMID- 25618936
TI  - Staffing changes/developments at NZNO.

PMID- 25618937
TI  - Gender equity on agenda at ICN workforce forum.

PMID- 25618939
TI  - Challenges for Health Workforce New Zealand.

PMID- 25618938
TI  - Pilot has 'mixed results'.

PMID- 25618940
TI  - High dependence on overseas doctors.

PMID- 25618941
TI  - NZ nurses respond to Ebola crisis.

PMID- 25618942
TI  - Study reveals challenges of ageing with an intellectual disability.

PMID- 25618944
TI  - Te Kakano nurse-led clinics aim to improve access for Maori.

PMID- 25618943
TI  - Janet Maloney-Moni leaves a lasting legacy.

PMID- 25618945
TI  - New graduate's life comes full circle.

PMID- 25618946
TI  - Nurses championing change.

PMID- 25618947
TI  - Continuing NZNO's advocacy.

PMID- 25618948
TI  - Campaigning the key to achieving change.

PMID- 25618950
TI  - How to achieve 'the perfect health system'.

PMID- 25618949
TI  - Protecting workers' health and safety.

PMID- 25618951
TI  - Award winner praises Northland Maori nurses.

PMID- 25618952
TI  - Mitigating against shift work hazards.

PMID- 25618953
TI  - TPPA could threaten the public health agenda.

PMID- 25618954
TI  - A neglected discipline.

PMID- 25618955
TI  - Providing secure care for those with an intellectual disability.

PMID- 25618956
TI  - Global Trigger Tool aims to keep patients safe.

PMID- 25618957
TI  - TrendCare and CCDM--nurse managers respond.

PMID- 25618958
TI  - Scrutinising the quality and validity of TrendCare data.

PMID- 25618959
TI  - Empowering staff to make changes.

PMID- 25618960
TI  - Balancing rights with responsibilities.

PMID- 25618961
TI  - College/section day: facing the questions.

PMID- 25618962
TI  - Nurse practitioners: focus on prescribing.

PMID- 25618963
TI  - DHB members decide on issues for negotiations.

PMID- 25618964
TI  - Primary health care: proposed MECA reached.

PMID- 25618965
TI  - Clinical curative effect of electric acupuncture on acute cerebral infarction: a
      randomized controlled multicenter trial.
AB  - OBJECTIVE: To examine whether electric acupuncture can improve the daily life of
      patients with ischemic cerebral apoplexy at acute stage. METHODS: A stratified
      block randomized controlled multicenter trial was designed for this study.
      Totally 340 patients with acute ischemic cerebral apoplexy were randomly divided
      into an electric acupuncture group and a control group. In the electric
      acupuncture group, 170 patients were treated with electric acupuncture and
      routine therapy, and 170 patients in the control group with routine therapy
      alone. Major indexes for judging curative effect were Barthel index at 3- and 6-
      months follow-up visits and number of re-hospitalized patients. Minor indexes for
      judging curative effect were change in the score for nervous dysfunction at 4 and
      12 weeks follow-up visits and number of patients persisting in rehabilitation
      treatment with acupuncture during follow-up visit. RESULTS: Baseline data at the
      time of case selection between the two groups were similar. The odds ratio (OR)
      was 0.92, and the 95% confidence interval (CI) was 0.49-1.73 in disabled rate and
      0.73 and 0.51-1.05 in the number of re-hospitalized patients in the electric
      acupuncture group at 6-month follow up visit compared with the control group.
      There was no difference in the score for nervous dysfunction at the end of 12
      week follow-up visit between the two groups. The score for nervous dysfunction at
      the end of 4-week treatment in the electric acupuncture group was significantly
      higher than that in the control group (P < 0.05). The number of patients
      discharged from hospital who persisted in rehabilitation treatment with
      acupuncture in the acupuncture group was significantly higher than that in the
      control group. CONCLUSION: Using electric acupuncture to treat patients with
      acute ischemic cerebral apoplexy can effectively improve the nervous dysfunction
      scores after 4-week treatment and their ability to deal with daily life after 6
      month follow-up visit. Systematic treatment with acupuncture may also reduce the
      number of patients with secondary apoplexy.

PMID- 25618966
TI  - Effect of ginseng polysaccharides and dendritic cells on the balance of Th1/Th2 T
      helper cells in patients with non-small cell lung cancer.
AB  - OBJECTIVE: To investigate the effect of thorascopic administration.of ginseng
      polysaccharides (GPS) plus dendritic cells (DC) on T helper cell type 1/T helper
      cell type 2 (Th1/Th2) balance in patients with non-small cell lung cancer
      (NSCLC). METHODS: A total of 96 NSCLC patients were divided evenly into two
      groups. The control group was treated with DCs alone and the treatment group was
      treated with DCs plus GPS. After DCs and GPS were administered thoracoscopically,
      once a week, 4 times for 30 days, the patients' quality of life was measured with
      the Functional Assessment of Cancer Treatment-Lung (FACT-L) questionnaire before
      and after treatment. Serum interferon-gamma (INF-gamma), interleukin-4 (IL-4), IL
      2 and IL-5 were examined before and after treatments. RESULTS: The level of Th1
      cytokines (INF-gamma, IL-2) and the ratio of Th1/Th2 cytokines (INF-gamma/IL-4,
      IL-2/ IL-5) increased in both treatment groups, while Th2 cytokines (IL-4, IL-5)
      and FACT-L scores decreased (P < 0.01). Furthermore, after treatment Th1
      cytokines (INF-gamma, IL-2) and the ratio of Th1/Th2 cytokines (INF-gamma/IL-4,
      IL-2/IL-5) were higher in the DCs + GPS group than in the control group (P <
      0.05). Conversely, FACT-L scores and Th2 cytokines (IL-4, IL-5) were higher in
      the control group than in the DCs + GPS group (P < 0.05). CONCLUSION: The
      treatment regime of DCs plus GPS had a greater effect on NSCLC patients' immune
      function as compared with DCs alone. This was evident by increased expression of
      Th1 cytokines (INF-gamma, IL-2) and the ratio of Th1/Th2 (INF-gamma/IL-4, IL-2/IL
      5), as well as by decreased FACT-L scores and the expression of Th2 cytokines (IL
      4, IL-5).

PMID- 25618967
TI  - Clinical study on treatment of chronic viral cholestatic hepatitis with
      chishaodanpi decoction.
AB  - OBJECTIVE: To observe the therapeutic effect of Chishaodanpi decoction (CSDPD) on
      chronic viral cholestatic hepatitis. METHODS: A total of 107 subjects with
      chronic viral cholestatic hepatitis were enrolled in our hospital from March 2007
      to November 2012. Patients were randomly divided into treatment (54 cases) and
      control groups (53 cases). The control group was treated with potassium magnesium
      aspartate, diammonium glycyrrhizinate, glucurolactone, vitamin C, and lamivudine,
      once a day. The treatment group was treated with modified CSDPD, 100 mL a time,
      twice a day, in addition to the treatment given to the control group. The
      patients in both groups were treated for 8 weeks. The main symptoms and signs
      were recorded every day throughout the clinical trial. Before and after the
      trial, changes in liver function including total bilirubin (TBil), direct
      bilirubin (DBil), total bile acid (TBA), and the activities of alkaline
      phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), and gamma-glutamyl transferase (gamma-GT), were all detected. Adverse
      reactions were also recorded. RESULTS: There were no differences in gender, age,
      disease duration, symptoms, signs, or laboratory findings between the two groups
      (P > 0.05). After an 8-week treatment, improvements in jaundice, weakness, poor
      appetite, abdominal distention, and skin itching were significantly better in the
      treatment group than in the control group (P < 0.05). In the treatment group, 43
      patients had a significant response to the treatment, seven patients had a
      response, and four patients had no response, with 21, 12, and 20 patients in the
      control group, respectively. The total effective rate was 92.6% in the treatment
      group and 62.3% in the control group, which was a significant difference (P <
      0.05). The levels of TBil, DBil, TBA, ALP, ALT, AST, and gamma-GT in both groups
      were significantly lower after treatment, and were significantly different
      between the two groups (P < 0.05). A few patients in the treatment group had mild
      adverse effects such as increased bowel movement frequency and mild stomach-ache.
      No other adverse reactions were observed in either group.

PMID- 25618968
TI  - Clinical treatment of depressive patients with anshendingzhi decoction.
AB  - OBJECTIVE: To determine the effects of Anshendingzhi decoction (ASDZD) on
      depression, to compare ASDZD with Danzhixiaoyao pill (DZXYP), and to provide
      evidence for the clinical treatment of depression with Traditional Chinese
      Medicine. METHODS: Seventy-eight patients with depression were enrolled from 2011
      to 2013 in this double-blinded study. Patients were randomly divided into two
      groups: ASDZD (treatment group, n = 39) and DZXYP (control group, n = 39).
      Hamilton Depressive Scale and TCM Syndrome Differentiation Scale were used to
      assess depression and efficacy before treatment and 2, 4, and 6 weeks after
      treatment. The Treatment Emergent Symptoms Scale (TESS) was used to evaluate
      adverse reactions, observe, and record treatment outcomes. RESULTS: ASDZD was
      significantly more effective than DZXYP. There were significant differences
      between the two groups in terms of recovered patients, overall response rate, and
      TESS score (all P < 0.05). CONCLUSION: ASDZD is an effective treatment for
      depression. ASDZD could improve clinical symptoms and warrants further clinical
      research and application.

PMID- 25618969
TI  - Xinfeng capsule improves pulmonary function in ankylosing spondylitis patients
      via NF-KappaB-iNOS-NO signaling pathway.
AB  - OBJECTIVE: To study changes in the nuclear factor-kappaB p65 (NF-kappaB p65)
      inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling pathway and
      the effects of Xinfeng capsules (XFC) in patients with ankylosing spondylitis
      (AS). METHODS: One hundred twenty patients with AS were randomly divided into an
      XFC group and a Salazopyrin group. Sixty health subjects were included as a
      normal control group. In the two treatment groups, pulmonary functional
      parameters, forced vital capacity (FVC), forced expiratory volume in 1 second
      (FEV1), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), forced
      expiratory flow at 25% of forced vital capacity (FEF25), forced expiratory flow
      at 50% of forced vital capacity (FEF50), and forced expiratory flow at 75% of
      forced vital capacity (FEF75) were determined. Enzyme linked immunosorbent assays
      were used for detection of the serum oxidative stress indexes, NF-kappaB p65,
      iNOS, NO, reactive oxygen species (ROS), reactive nitrogen species (RNS),
      malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total
      antioxidative capacity (TAOC) and interleukin-4 (IL-4), IL-10, IL-1beta, and
      tumor necrosis factor-alpha (TNF-alpha) contents. Westergren's method was used
      for determination of erythrocyte sedimentation rate (ESR). High-sensitivity C
      reactive protein (Hs-CRP) was detected with a 7060 full-automatic biochemical
      analyzer (Hitachi, Japan). RESULTS: The clinical therapeutic effect in the XFC
      group was significantly superior to that in the Salazopyrin group (P < 0.01).
      Compared with the normal control group, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT,
      TAOC, IL-4, IL-10 were significantly lower, and NF-kappaB p65, iNOS, NO, ROS,
      RNS, MDA, IL-1beta, TNF-alpha, ESR, and Hs-CRP significantly higher in patients
      with AS (P < 0.01 or P < 0.05). Compared with before treatment, FEV1, MVV, PEF,
      FEF50, FEF75, SOD, CAT, TAOC, IL-4, and IL-10 were significantly increased, and
      NF-kappaB p65, iNOS, NO, ROS, RNS, MDA, IL-1beta, TNF-alpha, ESR, CRP, visual
      analog scales (VAS), Bath ankylosing spondylitis disease active index, Bath
      ankylosing spondylitis functional index, and Bath ankylosing spondylitis global
      index significantly decreased in the two treatment groups after treatment (P <.
      0.01 or P < 0.05), with significant differences between the XFC and Salazopyrin
      groups (P < 0.01 or P < 0.05). Spearman correlation analysis indicated that FEV1,
      MWVV, PEF, FEF50, and FEF75 were positively correlated with SOD, CAT, TAOC, IL-4,
      and IL-10, and were negatively correlated with NF-kappaB p65, iNOS, NO, ROS, RNS,
      MDA, IL-13, TNF-alpha, ESR, and CRP. CONCLUSION: Patients with AS have local
      pathologic changes in the spinal cord and other joints. They also have decreased
      pulmonary function, which is negatively correlated with the NF-kappaB-iNOS-NO
      signaling pathway, oxidative indexes, and inflammatory factors. XFC improves
      rigidity and pain in spinal joints and other symptoms, laboratory indexes, and
      pulmonary function. The mechanism is possibly related to inhibition of the NF-KB
      iNOS-NO signaling pathway.

PMID- 25618970
TI  - Effect of a comprehensive therapy plus gushenyutai plaster administered at
      guanyuan (CV 4) on male infertility associated with semen non-liquefaction.
AB  - OBJECTIVE: To observe the clinical effect of Gushenyutai plaster administered at
      the Guanyuan (CV 4) acupoint on male infertility associated with semen non
      liquefaction. METHODS: Sixty-two male patients with infertility caused by semen
      non-liquefaction were randomized into a treatment and control group. The control
      group received comprehensive therapy, which included oral administration of
      clarithromycin sustained release tablets, hip bath with Zhongyaoxiaoyan granules,
      prostate massage, and transurethral microwave treatment. The treatment group was
      administered Gushenyutai plaster in addition to the comprehensive therapy. Both
      groups were treated for 8 weeks. After treatment, the clinical effect and
      pregnancy rate were assessed and compared between the two groups. RESULTS: The
      effective rate of the treatment group was significantly higher than that of the
      control group (96.77% vs 70.97%, P < 0.05) and the pregnancy rates of the
      treatment group and control groups were 38.71% and 16.13%, respectively (P <
      0.05). CONCLUSION: The effect of Gushenyutai plaster plus comprehensive therapy
      was better than that of the comprehensive therapy alone on male infertility
      induced by semen non-liquefaction.

PMID- 25618971
TI  - Effect of pulsatile perfusion during cardiopulmonary bypass in terms of radial
      artery sphygmogram.
AB  - OBJECTIVE: To investigate a quantitative method for using radial artery pulse
      waveforms to assess the effect of pulsatile flow during cardiopulmonary bypass
      (CPB). METHODS: A total of 34 adults with heart disease who underwent open-heart
      surgery between April 2010 and January 2011 were randomized into a pulsatile
      perfusion group (n = 17) and a non-pulsatile perfusion group (n = 17). Radial
      arterial pulse waveforms of pulsatile and non-pulsatile perfusion patients were
      observed and compared before and during CDB. RESULTS: No pulse waveform could be
      detected at patients' radial artery in both groups when the aorta was cross
      clamped. Pulse waveforms could be detected at pulsatile perfusion patients'
      radial artery, but could not be detected at non-pulsatile perfusion patients'
      radial artery during CPB. Additionally, patients' pulse waveforms during
      pulsatile perfusion were lower than those before the operation. CONCLUSION: Our
      findings indicate that radial artery sphygmogram can be used as a valid indicator
      to evaluate the effectiveness of pulsatile perfusion during CPB.

PMID- 25618972
TI  - Reversal effect of bufalin on multidrug resistance in K562/VCR vincristine
      resistant leukemia cell line.
AB  - OBJECTIVE: To probe insights into the reversal effect of bufalin on vincristine
      acquired multidrug resistance (MDR) in human leukemia cell line K562/VCR.
      METHODS: Proliferative inhibition rate and the reversal index (RI) of bufalin
      were determined by Methyl thiazolyl tetrazolium assay. The uptake of Adriamycin
      (ADM) in K562/VCR cells, cell cycle and apoptosis rate were determined by flow
      cytometry (FCM). Cell morphologic changes were observed with Wright-Giemsa
      staining. The expression of P-glycoprotein (P-gp), multidrug-associated protein-1
      (MRP1), Bcl-xL and Bax protein were measured by immunocytochemistry. RESULTS: The
      human leukemia multidrug resistant K562/VCR cells showed no cross-resistance to
      bufalin. The RIs of bufalin at concentrations of 0.0002, 0.001 and 0.005 MUmol/L
      were 4.85, 6.94 and 14.77, respectively. Preincubation of 0.001 MUmol/L bufalin
      for 2 h could increase intracellular ADM fluorescence intensity to 28.07% (P <
      0.05) and down-regulate MRP1 expression simultaneously, but no remarkable effect
      was found on P-gp protein. Cell cycle analysis indicated increased apoptosis rate
      and apparent decreased G2/M phase proportion after treatment with bufalin. When
      exposed to 0.01 MUmol/L bufalin, typical morphological changes of apoptosis could
      be observed. Down-regulation of Bcl-xL and up-regulation of Bax expression in
      K562/VCR cells could be detected by immunocytochemistry. CONCLUSION: Bufalin
      could partly reverse the MDR of K562/VCR cells, with a possible mechanism of down
      regulating MRP1 expression and activating apoptosis pathway by altering Bcl
      xL/Bax ratio.

PMID- 25618973
TI  - Electroacupuncture inhibits annulus fibrosis cell apoptosis in vivo via TNF-alpha
      TNFR1-caspase-8 and integrin beta1/Akt signaling pathways.
AB  - OBJECTIVE: To examine whether electroacupuncture (EA) treatment inhibited cell
      apoptosis of intervertebral annulus fibrosis (AF) via tumor necrosis factor-alpha
      (TNF-alpha)-tumor necrosis factor receptor 1 (TNFR1)-caspase-8 and integrin
      beta1/Akt signaling pathways in a rat model of cervical intervertebral disc
      degeneration caused by unbalanced dynamic and static forces. METHODS: Thirty-two
      Sprague-Dawley rats were included in this study, of which 24 rats underwent
      surgery to induce cervical intervertebral disc degeneration, while eight rats
      received EA treatment at Dazhui (GV 14). Immunohistochemical staining was used to
      detect TNF-alpha, TNFR1, and caspase-8. Apoptosis of AF cells was examined with
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) staining. The mRNA and protein expression levels of integrin beta1 and
      Akt were evaluated with real-time polymerase chain reaction and western blot
      analysis, respectively. RESULTS: Treatment with EA decreased TUNEL-positive AF
      cells and lowered TNF-alpha, TNFR1 and caspase-8 positive cells compared with
      control groups. EA treatment also increased integrin beta1 and Akt mRNA and
      protein levels compared with controls. CONCLUSION: Treatment with EA inhibits AF
      cell apoptosis through suppression of the TNF-alpha-TNFR1-caspase-8 signal
      pathway and increases the expression of integrin beta1 and Akt. EA may be a good
      alternative therapy for treating cervical spondylosis.

PMID- 25618974
TI  - Pituitary transcriptome profile of liver cancer mice with different syndromes
      reveals the relevance of pituitary to the cancer and syndromes.
AB  - OBJECTIVE: To investigate the relevance of the pituitary to liver syndromes and
      cancer by studying the pituitary transcriptome profile in liver cancer mice with
      different syndromes. METHODS: The quantitative four diagnosis and syndrome
      differentiation methods were used to screen normal control mice without syndromes
      (NC), liver cancer mice with poisonous pathogenic factors syndrome (PPFS), and Qi
      deficiency syndrome mice (QDS). An Affymetrix GeneChip Mouse Exon 1.0 ST Array
      was performed to detect the gene expression of different groups. Gene clustering
      was applied to analyze the gene expression patterns of the PPFS and QDS groups
      compared with the NC group. The transcriptional networks analysis tool, FunNet,
      was used to enrich the biological categories of differentially expressed genes in
      the PPFS and QDS groups. RESULTS: Biological categories of differentially
      expressed genes showed that excessive metabolism and extracellular matrix
      interaction, insufficient communication of cells (especially nerve cells), and
      the bidirectional regulation of genetic information processing were enriched in
      both syndromes. However, the degree of excessive metabolism in the PPFS group was
      higher than that in the QDS group. The hyperfunction of cancer and infection, and
      the hypofunction of the nervous and endocrine systems were obvious in the QDS
      group. CONCLUSION: The pituitary plays an important role in the development of
      liver cancer and syndromes. This study further studied the role of the pituitary
      in the combination of disease and syndromes.

PMID- 25618975
TI  - Protective effects of yindanxinnaotong capsule in a rat model of myocardial
      ischemia/reperfusion injury.
AB  - OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule (YDXNTC) and
      main components compatibility and ratios on myocardium against
      ischemia/reperfusion injury and the effect's underlying mechanism. METHODS:
      Myocardial ischemia/reperfusion injury (MIRI) was induced by ischemia for 30 min
      and reperfusion for 30 min. Electrocardiogram data and coronary flow were
      recorded, and superoxide dismutase (SOD), malondialdehyde (MDA), lactate
      dehydrogenase, creatine kinase-MB, cardiac troponin T and I (cTnT, cTnI) and
      interleukin-1beta, interleukin-8, interleukin-18 (IL-1beta, IL-8, IL-18) in
      myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide (H2O2)
      injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 MUM H2O2
      for 1 h, respectively, in vitro rat myocardial cells (H9c2). Cell viability, SOD,
      MDA, cTnT and inflammatory factors (IL-1beta, IL-8 and IL-18) were determined,
      and Toll-like receptor 4 (TLR-4) expression was measured by western blotting.
      RESULTS: In the isolated heart experiment, elevated heart function, coronary flow
      and SOD levels, and decreased MDA levels and inflammatory factors were noted in
      the YDXNTC, main components and main components compatibility groups. Ventricular
      tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba
      extract (GBE), and GBE and salvia miltiorrhiza ethanol extract compatibility (SM
      E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous
      extract of salvia miltiorrhiza (SM-H) groups. Creatine kinase-MB decreased with
      GBE, SM-E, SM-H and GSEC treatment, and cTnI and cTnT levels decreased with GSEC.
      In the in vitro cell study, YDXNTC and main components ratios improved cell
      viability and SOD levels, and suppressed MDA, cTnT and inflammatory factors. TLR
      4 expression was down-regulated. CONCLUSION: YDXNTC and main components
      compatibility showed protective effects on MIRI in this rat model and in vitro
      study. Regulating the Toll-like receptor signaling pathway may affect the
      mechanism.

PMID- 25618976
TI  - Electroacupuncture of neiguan (PC 6) inhibits enhanced voltage-gated sodium
      currents in ischemic ventricular myocytes.
AB  - OBJECTIVE: To examine the effect of electroacupuncture (EA) at bilateral Neiguan
      (PC 6) on voltage-gated Na+ currents (I(Na)) and channels (Na(v)) in ischemic
      ventricular myocytes. METHODS: EA serum was prepared from six male adult Sprague
      Dawley rats that had received EA at bilateral Neiguan (PC 6). Eighteen
      ventricular myocytes were prepared from six SD rats using an enzymolysis
      approach. Myocardial ischemia was mimicked by perfusion of ischemic solution.
      Whole-cell patch-clamping was used to record three currents evoked from isolated
      cells. The first current was the control, and recorded in absence of ischemic
      solution current. The second was the ischemic current, and recorded after
      perfusion of ischemic solution for 5 min, while the EA current was last, and
      recorded after perfusion of EA serum for 5 min. Na(v) kinetic curves were fitted
      using related formulas. RESULTS: Compared with those in controls, in the presence
      of ischemic solution, peak amplitudes of I(Na) significantly increased from - 40
      mV to +30 mV, and half-maximal inactivation potentials of Na(v) increased
      significantly, while half-maximal activation potentials, slope factors and the
      recovery time from inactivation to activation of Na(v) were unchanged. Compared
      with those in the ischemic solution, in the presence of EA serum, peak ischemic
      current amplitudes significantly reduced from - 40 mV to +40 mV, and half-maximal
      inactivation potentials were restored, while half-maximal activation potentials,
      slope factors and the recovery time from inactivation to activation of Na(v) were
      unchanged. CONCLUSION: EA at bilateral Neiguan (PC 6) can reduce enhanced I(Na)
      via restoration of delayed Na(v) inactivation in ischemic ventricular myocytes.

PMID- 25618977
TI  - Effect of volatile oil from Blumea Balsamifera (L.) DC. leaves on wound healing
      in mice.
AB  - OBJECTIVE: To assess the effectiveness of violate oil from Blumea Balsamifera
      (L.) DC. leaves (BB oil) on wound healing in mice. METHODS: Undiluted BB oil and
      its diluted solutions with olive oil to 1/5 and 1/10 to yield BB oil1/5 and BB
      oil1/10 were applied to the wounded skin before wound healing conditions were
      assessed by healing rate, histopathology, and contents of collagen,
      hydroxyproline, and Neuropeptide Substance P (SP). All above results were
      compared with the efficacies of the control, pure olive oil, basic fibroblast
      growth factor (BFGF), and cream of Jing Wan Hong (JWH). RESULTS: BB oil1/5 and BB
      oil1/10 improved wound contraction and closure. Histopathology study further
      confirmed a desirable histological organization of wound tissues. BB oil1/5 and
      BB oil1/10 reduced the number of inflammatory cells, increased wound-healing
      rates, and significantly increased the hydroxyproline content. Both BB oil1/5 and
      BB oil1/10 improved formation of collagen, and reduced the frequency of
      fibroblasts. Moreover, BB oil1/5 and BB oil1/10 markedly promoted SP expression.
      However, undiluted BB oil may induce skin thickening and hardening, inhibite
      collagen synthesis and delay complete skin wound healing. CONCLUSION: The BB
      oil1/5 and BB oil1/10 promoted capillary regeneration, blood circulation,
      collagen deposition, granular tissue formation, epithelial deposition, and wound
      contraction. The mechanism underlying the action might be related to induction of
      SP secretion, and the proliferation and differentiation of mesenchymal cells.

PMID- 25618978
TI  - Effect of tongluojiunao injection made from sanqi (Radix Notoginseng) and zhizi
      (Fructus Gardeniae) on brain microvascular endothelial cells and astrocytes in an
      in vitro ischemic model.
AB  - OBJECTIVE: To explore the effect of Tongluojiunao injection (TLJN) prepared with
      Sanqi (Radix Notoginseng) and Zhizi (Fructus Gardeniae) on the interaction
      between brain microvascular endothelial cells (BMECs) and astrocytes in an in
      vitro ischemic model. METHODS: First, an in vitro model of cerebral ischemia in
      BMECs or astrocytes was established by oxygen-glucose deprivation (OGD). TLJN was
      used as a medicine of intervention. The OGD-injured BMECs were cultured in
      various astrocyte-conditioned media. Cell activity, alkaline phosphatase (AKP)
      and gamma-glutamyl transpeptidase (gamma-GT) activity, interleukin-1 beta (IL
      1beta), and tumor necrosis factor alpha (TNF-alpha) content in BMECs were
      determined. Additionally, OGD-injured astrocytes were cultured in various BMEC
      conditioned media. Cell activity, as well as expression of brain-derived
      neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in
      astrocytes, were detected. RESULTS: The results of paracrine signaling of normal
      BMECs or astrocytes showed a protective effect on each other: conditioned media
      from normal astrocytes improved cell viability, AKP, and gamma-GT activity, and
      reduced IL-1beta and TNF-alpha content of injured BMECs; conditioned media from
      normal BMECs improved cell viability and expression of BDNF and GDNF in injured
      astrocytes. However, once the BMECs or astrocytes were injured by OGD, the
      protective effect decreased or disappeared. The above-mentioned protective
      induction was effectively recovered by TLJN intervention. CONCLUSION: The
      therapeutic benefit of TLJN was achieved by recovering two-way induction between
      BMECs and astrocytes, enhancing activity of injured BMECs and astrocytes,
      stabilizing enzymatic barriers, promoting expression of neurotrophic factors, and
      inhibiting inflammatory cytokines.

PMID- 25618979
TI  - Antioxidant and immunomodulatory activities of a polysaccharide from Flammulina
      velutipes.
AB  - OBJECTIVE: To evaluate the antioxidant and immunomodulatory activities of a
      unique polysaccharide from the medicinal fungus Flammulina velutipes in vitro.
      METHODS: Using water extraction and alcohol precipitation, crude polysaccharides
      were obtained. After purification by DEAE-cellulose 52 ion exchange
      chromatography and Sephacryl S-300 HR gel filtration chromatography, High
      performance liquid chromatography equipped with evaporative light-scattering
      detector, Infrared radiation and Nuclear magnetic resonance were used to evaluate
      the structure of the polysaccharide. Its immunomodulatory activity was measured
      by examining the production of nitric oxide (NO) and cytokine secretion, and via
      lymphocyte proliferation experiments. Its effects on the scavenging activities of
      hydroxyl radical, superoxide anion and reducing power were also measured.
      RESULTS: A water-soluble polysaccharide, Flammulina velutipes polysaccharide I-A
      (FVP I-A), was obtained with a molecular mass of 8.14 x 10(4) Da determined by
      high performance gel permeation chromatography. An in vitro antioxidant assay
      indicated that FVP I-A could scavenge hydroxyl radical, superoxide anion and
      possessed reducing power and could largely promote NO production and augment the
      interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha secretion by
      RAW264.7 macrophages (P < 0.05). Moreover, FVP I-A could promote lymphocyte
      proliferation (P < 0.05), and synergistically enhance the augmentation of the
      proliferation of mouse lymphocytes by concanavalin A and lipopolysaccharides (P <
      0.01, P < 0.05). CONCLUSION: The FVP I-A obtained from Flammulina velutipes
      possessed antioxidant activity and could enhance non-specific and specific immune
      responses in vitro.

PMID- 25618980
TI  - Gas chromatography-mass spectrometry analysis of essential oils from five parts
      of Chaihu (Radix Bupleuri Chinensis).
AB  - OBJECTIVE: To analyze the essential oils from flowers, leaves, stems, roots, and
      fruits of Chaihu (Radix Bupleuri Chinensis). METHODS: We extracted essential oils
      from different parts of Chaihu (Radix Bupleuri Chinensis) using a steam
      distillation method. The essential oils were analyzed by gas chromatography-mass
      spectrometry (GC-MS). Data were collected in full scan mode (m/z 60-600).
      Volatile components were identified based on their retention indices and by
      comparing their mass spectra with those in the National Institute of Standards
      and Technology 2005 database, assisted by tandem mass spectrometry information.
      The relative content of each constituent was determined by area normalization.
      RESULTS: We identified 111 components, of which 12 were common to all 5 parts, 30
      were found only in roots, 14 were found only in flowers, 6 were found only in
      leaves, 4 were found only in stems, and 17 were found only in fruits. CONCLUSION:
      Our results show that the stems, flowers, leaves, and fruits of Chaihu (Radix
      Bupleuri Chinensis) contain a high concentration of essential oils, and that the
      exact composition of the essential oils differs among the plant parts. To develop
      new medicines and make full use of the Chaihu (Radix Bupleuri Chinensis)
      resource, it is important to characterize the essential oils from different parts
      of the plant. In future research, it will be important to determine the
      pharmacological effects of the various components and the essential oil mixtures.

PMID- 25618981
TI  - Postmarketing safety evaluation: depside salt injection made from Danshen (Radix
      Salviae Miltiorrhizae).
AB  - OBJECTIVE: To systematically examine the post-marketing safety of depside salt
      injection made from Danshen (Radix Salviae Miltiorrhizae), identify the potential
      risk factors, and ensure its clinical safety. METHODS: We examined a
      comprehensive series of studies on the production process, quality standards,
      pharmacology, population pharmacokinetics, and safety evaluation of depside salt
      injection made from Danshen (Radix Salviae Miltiorrhizae). Data from I-IV
      clinical drug trials, hospital information systems (HIS), and spontaneous
      reporting systems (SRS) were also analyzed. RESULTS: The effective components of
      salvianolic acid salt content reached almost 100%, and the magnesium
      lithospermate B content reached more than 80%. The median lethal dose (LD50)
      calculated by the Bliss method was 1.49 g/kg, with 95% confidence intervals of
      1.29-1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than
      80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions
      (ADRs) included digestive disorders; drug-induced erythrocyte deformation in
      lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and
      other tissues; megakaryocytes in lung, liver, and spleen resulting from mild
      hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other
      studies indicated no irritative effect of the injection on local tissues and
      blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis.
      SRS data showed that the most common ADRs were headache, head distention,
      dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility
      of elevated Aspartate transaminase. HIS data indicated no damage to renal
      function from using depside salt injection made from Danshen (Radix Salviae
      Miltiorrhizae) at a dosage higher than the recommended dose. CONCLUSION: This
      study analyzes the clinical characteristics of ADRs from depside salt injection
      made from Danshen (Radix Salviae Miltiorrhizae), and discusses the factors
      influencing such reactions. It provides scientific reference and recommendations
      for clinically safe medication of the Danshen injection.

PMID- 25618982
TI  - Different manual manipulations and electrical parameters exert different
      therapeutic effects of acupuncture.
AB  - Acupuncture is an important component part of Traditional Chinese Medicine (TCM).
      The therapeutic effects may be influenced by a variety of factors. Stimulation
      quantity is one of the factors for achieving good therapeutic effects in
      acupuncture practice. With the development of science and technology, besides the
      influence of manual manipulations, the parameters adopted for electroacupuncture
      have become the benchmark of stimulation quantity. This study, by referring to
      the related literatures, is designed to explore the influence of manual
      manipulations and electrical parameters on therapeutic effects of acupuncture.
      The results from the present study show that different manual manipulations and
      electrical parameters may exert different therapeutic effects of acupuncture,
      which are closely related to the characteristics of diseases. Different manual
      manipulations and electrical parameters should be adopted according to syndrome
      differentiation of TCM. This is very important in acupuncture treatment.

PMID- 25618983
TI  - Realist identification of group-level latent variables for perinatal social
      epidemiology theory building.
AB  - We have previously reported in this journal on an ecological study of perinatal
      depressive symptoms in South Western Sydney. In that article, we briefly reported
      on a factor analysis that was utilized to identify empirical indicators for
      analysis. In this article, we report on the mixed method approach that was used
      to identify those latent variables. Social epidemiology has been slow to embrace
      a latent variable approach to the study of social, political, economic, and
      cultural structures and mechanisms, partly for philosophical reasons. Critical
      realist ontology and epistemology have been advocated as an appropriate
      methodological approach to both theory building and theory testing in the health
      sciences. We describe here an emergent mixed method approach that uses
      qualitative methods to identify latent constructs followed by factor analysis
      using empirical indicators chosen to measure identified qualitative codes.
      Comparative analysis of the findings is reported together with a limited
      description of realist approaches to abstract reasoning.

PMID- 25618984
TI  - Distinguishing the race-specific effects of income inequality and mortality in
      U.S. metropolitan areas.
AB  - In the United States, the association between income inequality and mortality has
      been fairly consistent. However, few studies have explicitly examined the impact
      of race. Studies that have either stratified outcomes by race or conducted
      analyses within race-specific groups suggest that the income inequality/mortality
      relation may differ for blacks and whites. The factors explaining the association
      may also differ for the two groups. Multivariate ordinary least squares
      regression analysis was used to examine associations between study variables. We
      used three measures of income inequality to examine the association between
      income inequality and age-adjusted all-cause mortality among blacks and whites
      separately. We also examined the role of racial residential segregation and
      concentrated poverty in explaining associations among groups. Metropolitan areas
      were included if they had a population of at least 100,000 and were at least 10
      percent black. There was a positive income inequality/mortality association among
      blacks and an inverse association among whites. Racial residential segregation
      completely attenuated the income inequality/mortality relationship for blacks,
      but was not significant among whites. Concentrated poverty was a significant
      predictor of mortality rates in both groups but did not confound associations.
      The implications of these findings and directions for future research are
      discussed.

PMID- 25618985
TI  - All things being equal: does it matter for equity how you organize and pay for
      health care? A review of the international evidence.
AB  - Over the last 25 years, the health care systems of most high-income countries
      have experienced extensive--usually market-based--organizational and financial
      reforms. The impact of these system changes on health equity has been hotly
      debated. Examining evidence from systematic reviews of the effects of health care
      system organizational and financial reforms will add empirical information to
      this debate, identify any evidence gaps, and help policy development. Systematic
      review methodology was used to locate and evaluate published systematic reviews
      of quantitative intervention studies (experimental and observational) of the
      effects on equity in health care access and/or health status of health care
      system organizational and financial reforms (system financing, funding
      allocations, direct purchasing arrangements, organization of service provision,
      and health and social care system integration) in high-income countries. Nine
      systematic reviews were identified. Private insurance and out-of-pocket payments
      as well as the marketization and privatization of services have either negative
      or inconclusive equity effects. The evidence base on the health equity effects of
      managed care programs or integrated partnerships between health and social
      services is inconclusive. There were no relevant studies located that related to
      resource allocation reforms. The systematic review-level evidence base suggests
      that financial and organizational health care system reforms have had either
      inconclusive or negative impacts on health equity both in terms of access
      relative to need and in terms of health outcomes.

PMID- 25618986
TI  - Quality check: does it matter for quality how you organize and pay for health
      care? A review of the international evidence.
AB  - Health systems in high-income countries have experienced significant
      organizational and financial reforms over the last 25 years. The implications of
      these changes for the effectiveness of health care systems need to be examined,
      particularly in relation to their effects on the quality of health services (a
      pertinent issue in the United Kingdom in light of the Francis Report). Systematic
      review methodology was used to locate and evaluate published systematic reviews
      of quantitative intervention studies (experimental and observational) on the
      effects of health system organizational and financial reforms (system financing,
      funding allocations, direct purchasing arrangements, organization of service
      provision, and service integration) on quality of care in high-income countries.
      Nineteen systematic reviews were identified. The evidence on the payment of
      providers and purchaser-provider splits was inconclusive. In contrast, there is
      some evidence that greater integration of services can benefit patients. There
      were no relevant studies located relating to funding allocation reforms or direct
      purchasing arrangements. The systematic review-level evidence base suggests that
      the privatization and marketization of health care systems does not improve
      quality, with most financial and organizational reforms having either
      inconclusive or negative effects.

PMID- 25618987
TI  - Why public health services? Experiences from profit-driven health care reforms in
      Sweden.
AB  - Market-oriented health care reforms have been implemented in the tax-financed
      Swedish health care system from 1990 to 2013. The first phase of these reforms
      was the introduction of new public management systems, where public health
      centers and public hospitals were to act as private firms in an internal health
      care market. A second phase saw an increase of tax-financed private for-profit
      providers. A third phase can now be envisaged with increased private financing of
      essential health services. The main evidence-based effects of these markets and
      profit-driven reforms can be summarized as follows: efficiency is typically
      reduced but rarely increased; profit and tax evasion are a drain on resources for
      health care; geographical and social inequities are widened while the number of
      tax-financed providers increases; patients with major multi-health problems are
      often given lower priority than patients with minor health problems;
      opportunities to control the quality of care are reduced; tax-financed private
      for-profit providers facilitate increased private financing; and market forces
      and commercial interests undermine the power of democratic institutions. Policy
      options to promote further development of a nonprofit health care system are
      highlighted.

PMID- 25618988
TI  - Public insurance is increasingly crucial to American families even as employer
      sponsored health insurance coverage ends its steady decline.
AB  - Americans under age 65 rely on a healthy labor market for almost all facets of
      economic security. While 2012 marked the first year in more than a decade that
      the employer-sponsored health insurance (ESI) coverage rate for the under-65
      population did not decline, employer-sponsored health insurance continues to fail
      American families. If the coverage rate had not fallen 10.8 percentage points as
      it did from 2000 to 2012, as many as 29 million more people under age 65 would
      have had ESI in 2012. Even with the end of its longstanding decline, ESI coverage
      rates among men and women, white and non-white, high and low income, white and
      blue collar, young and old remain far lower than they were in 2000. Over this
      period, the increase in uninsured Americans was not as steep as the fall in ESI
      because of increases in public coverage, including Medicaid, the Children's
      Health Insurance Program, and Medicare. These programs were particularly
      effective in reducing the share of children uninsured over the 2000s.
      Additionally, key components in the Patient Protection and Affordable Care Act
      shielded young adults from further coverage losses.

PMID- 25618989
TI  - Using comparative analysis to address health system caricatures.
AB  - To learn from health care systems abroad, we must move beyond simplistic
      characterizations and compare different systems with respect to salient
      performance measures. Despite findings from recent cross-national studies
      suggesting that many health care systems outperform the United States, claims by
      U.S. public officials often fail to acknowledge the actual accomplishments of
      health care systems abroad. We document significant variation among the United
      States and France, Germany, and England, which provide universal coverage, albeit
      in different ways. As previously documented, the United States has the highest
      rate of mortality amenable to health care. We extend this work by adding two
      indicators: (a) access to timely and effective primary care as measured by
      hospital discharges for avoidable hospital conditions; and (b) use of specialty
      services as indicated by coronary revascularization (bypass surgery and
      angioplasty), adjusted for the burden of coronary artery disease. Our findings
      indicate that: (a) the United States suffers the gravest consequences of
      financial barriers to primary care; (b) in all four countries, older people (65+)
      receive fewer revascularizations than their younger counterparts once we account
      for disease burden; and (c) in France, patients receive the most
      revascularizations, after adjusting for the burden of disease.

PMID- 25618990
TI  - Enhancing physician engagement: an international perspective.
AB  - The purpose of this article is to provide specific recommendations to enhance
      physician engagement in health care organizations. It summarizes the evidence on
      physician engagement, drawing on peer-reviewed articles and reports from the gray
      literature, and suggests an integrative framework to help health care managers
      better understand and improve physician engagement. While we examine some other
      international examples and experiences, we mainly focus on physician engagement
      in Canada, the United States, and the United Kingdom. Physician engagement can be
      conceptualized as an ongoing two-way social process in which both the individual
      and organizational/cultural components are considered. Building on several
      frameworks and examples, we propose a new integrative framework for enhancing
      physician engagement in health care organizations. We suggest that in order to
      enhance physician engagement, organizations should focus on the following
      strategies: developing clear and efficient communication channels with
      physicians; building trust, understanding, and respect with physicians; and
      identifying and developing physician leaders. We propose that the time is now for
      health care managers to set aside traditional differences and historical
      conflicts and to engage their physicians for the betterment of their
      organizations.

PMID- 25618991
TI  - Perceptions of Turkish dentists of their professional identity in a market
      orientated system.
AB  - This study explores the perceptions of Turkish dentists of their professional
      identity and of the effects of market orientation in dentistry. This
      phenomenological study used a qualitative approach using a group of Turkish
      dentists, who were selected based on the principle of maximum variation. Four
      focus groups and 31 in-depth interviews were conducted. Forty-nine dentists were
      interviewed using a semi-structured form. The data analysis yielded three themes:
      (a) dentistry as a business; (b) dentistry as a profession; and (c) professional
      status of dentistry in the health care system and in the community. The
      participants' statements reflected that the dominance of market mechanisms in
      dentistry inevitably forces dentists to adopt the characteristics of a business
      person and prevents them from fulfilling the basic requirements of
      professionalism. All participants explained that with the transformation of the
      dental care market, dentists have become a cheap labor force and have lost their
      professional autonomy. Our study has confirmed previous reports pointing out the
      conflict between dentistry as a profession and dentistry as a commercial
      operation. The study also showed that in Turkey, as a country experiencing rapid
      reform processes, dentists' control over their professional practices and
      identities has decreased.

PMID- 25618993
TI  - Louis van der Heide: 1933-2014.

PMID- 25618992
TI  - Failing ethics 101: psychologists, the U.S. military establishment, and human
      rights.
AB  - The American Psychological Association (APA) has long maintained a close, even
      symbiotic, relationship with the Department of Defense (DOD) and the Veterans
      Administration (VA). Herein we highlight these close ties and describe
      psychologists' participation in interrogations by U.S. military and intelligence
      entities. We then review the APA's statements about the permissibility of
      psychologist participation in the interrogation and torture of suspected
      terrorists. These issues are significant in and of themselves and because the VA
      and DOD have been described as "growth careers" for psychologists of the future
      (1). Additionally, the Health Care Personnel Delivery System allows the drafting
      of civilian clinical psychologists into military service even in the absence of a
      general draft. In light of psychologists' extensive involvement in the
      interrogation process of suspected terrorists, and the possibility that
      psychologists without prior military experience may be drafted, we wondered how
      much psychologists have been taught about their ethical duties should they find
      themselves in military settings. The results of our pilot study of U.S.
      psychology graduate students, which assessed their knowledge of military ethics,
      raise concerns that psychologists receive inadequate formal training in these
      matters. This may leave psychologists vulnerable to misinformation about proper
      ethical conduct in their future work.

PMID- 25618994
TI  - Salmonella Enteritidis infection slows steroidogenesis and impedes cell growth in
      hen granulosa cells.
AB  - Infection by Salmonella Enteritidis (SE) causes decreased egg production in
      laying hens. Immunoresponse, steroidogenesis, and cell proliferation by chicken
      granulosa cells (cGCs) are of particular interest because these changes are
      involved in follicular growth, atresia, and ovulation. To elucidate the possible
      mechanisms underlying these changes, transcriptional alterations in cGCs at
      distinct stages of follicular maturity were studied. Luteinizing hormone (LH)-and
      follicle-stimulating hormone (FSH) were applied to the cGCs isolated from
      hierarchical and prehierarchical follicles, respectively, to imitate the effects
      of gonadotropin during in vitro SE infection. Results showed that the expression
      of Toll-like receptor 15 was dependent on the follicular maturity, with mature
      cells having a more significant and progressively stronger immunoresponse.
      Attenuated responses to LH and FSH as well as retardant steroidogenesis due to
      down-regulated LH receptor, FSH receptor, and the P450 side-chain cleavage system
      were observed and may have led to delayed hierarchical follicular growth.
      Deteriorated cell viability of prehierarchical follicles may occur, as the
      proliferation of stimulator heparin-binding epidermal growth factor was reduced
      significantly. Furthermore, the infection led to a higher probability of cGCs
      from the smaller follicles undergoing apoptosis than those from F1 follicles.
      Collectively, the data provide evidence of a tendency toward pathogen elimination
      in F1 follicles by induction of a strong immune response and cell apoptosis in
      smaller follicles to avoid bacterial transovarian infection. It is our
      speculation that slowed steroidogenesis and impeded follicular growth may play
      essential roles in decreased ovulation rate as well as further decreased egg
      production during SE infection.

PMID- 25618995
TI  - Hemorrhagic nephritis and enteritis in a goose flock in Poland--disease course
      analysis and characterization of etiologic agent.
AB  - Hemorrhagic nephritis enteritis of geese (HNEG) is an epizootic viral disease
      caused by infection with goose hemorrhagic polyomavirus (GHPV) that affects
      domestic geese. This study describes the epizootic analysis, laboratory
      diagnosis, and molecular characterization of GHPV isolates associated with HNEG
      cases in Poland. HNEG symptoms persisted in infected flocks for 2 wk with a 32%
      mortality rate. Primary gross lesions included hemorrhaging of the kidneys,
      intestines, and lungs. Histopathologic examination confirmed HNEG and identified
      that the causative agent was similar to other GHPV isolates and identical to the
      Toulouse 2008 isolate.

PMID- 25618996
TI  - Experimental infection of different species of birds with pigeon paramyxovirus
      type 1 virus--evaluation of clinical outcomes, viral shedding, and distribution
      in tissues.
AB  - The virulence of pigeon paramyxovirus type 1 (PPMV-1) for different species of
      birds was investigated in two independent sets of experiments in which groups of
      pigeons, chickens, turkeys, quails, and geese (10 birds per group) were
      inoculated with 10(6) median embryo infectious doses of PPMV-1 isolate: 1)
      nonpassaged (nPPMV-1, intracerebral pathogenicity [ICPI] value = 1.27) and 2)
      after six passages in specific-pathogen-free chickens (pPPMV-1, ICPI = 1.46) via
      the oculonasal route. Naive birds were placed in contact with infected birds (two
      birds per group) to monitor virus transmission. Clinical observation was
      performed daily. Additionally, cloacal swabs, oropharyngeal swabs, and selected
      organ samples were collected on days 2, 4, 7, 10, and 14 postinfection and tested
      by real-time reverse transcriptase-PCR for estimation of viral shedding and
      distribution in tissues. Infected pigeons exhibited nervous and digestive tract
      symptoms, mortality, shedding, and transmission to contact birds. Chickens,
      turkeys, quails, and geese did not exhibit any clinical signs regardless of the
      PPMV-1 strain used for inoculation. However, in contrast to quails and geese,
      chickens and turkeys shed the virus via the oral cavity and cloaca, and
      transmission to contact birds was also observed. Viral RNA was identified in
      tissues collected from all pPPMV-1-infected birds, whereas negative results were
      obtained in the case of tissues taken from nPPMV-1-infected quails and geese. We
      conclude that the PPMV-1 used in this study was most virulent to pigeons,
      followed by chickens and turkeys, while quails and geese seem to have the highest
      level of innate resistance to this strain. However, passaging of PPMV-1 in
      chickens resulted in the increase of ICPI and noticeable but sometimes
      contrasting changes in the replication capacities of the virus.

PMID- 25618997
TI  - Avian influenza virus prevalence in migratory waterfowl in the United States,
      2007-2009.
AB  - We analyzed 155,535 samples collected for surveillance of avian influenza viruses
      (AIVs), in the United States from 2007 to 2009, from migratory waterfowl (ducks,
      geese, and swans). The goal was to elucidate patterns of prevalence by flyway and
      functional groups to determine targets for future surveillance. Apparent
      prevalence of AIV was highest in the Pacific Flyway in 2007-2008 (14.2% and
      14.1%, respectively), in the Mississippi Flyway in 2009 (16.8%), and lowest each
      year in the Atlantic Flyway (range, 7.3%-8.9%). Dabbling ducks had higher
      apparent prevalence of AIV (12.8%-18.8%) than diving ducks (3.9%-6.0%) or geese
      and swans (3.6%-3.9%). We observed highest apparent prevalence in hatch-year
      waterfowl (15.6%-18.9%). We further analyzed 117,738 of the 155,535 samples to
      test the hypothesis mallard (Anasplatyrhynchos) had highest prevalence of AIV. We
      compared apparent prevalence and odds ratios for seven species of ducks and one
      species of goose commonly collected across the United States. Mallards had
      highest apparent prevalence (15%-26%) in half of comparisons made, whereas
      American green- winged teal (Anas creeca, 12%-13%), blue-winged teal (Anas
      discors, 13%-23%), northern pintail (Anas acuta, 16%-22%), or northern shoveler
      (Anas clypeata, 15%) had higher apparent prevalence in the remaining comparisons.
      The results of our research can be used to tailor future surveillance that
      targets flyways, functional groups, and species with the highest probability of
      detecting AIV.

PMID- 25618998
TI  - Expression, purification, and in vitro comparative characterization of avian beta
      defensin-2, -6, and -12.
AB  - The mature peptides of avian beta-defensin-2 (AvBD-2), AvBD-6, and AvBD-12 were
      expressed as 6xHis-tagged recombinant proteins using the Escherichia coli
      BL21(DE3)pLysS system. The yields of rAvBD-2, rAvBD-6, and rAvBD-12 were
      approximately 0.92 mg/L, 1.24 mg/L, and 1.52 mg/L, respectively, of bacterial
      culture. The antimicrobial activities of rAvBDs were characterized under
      different salt, nutrient, and pH conditions. At concentrations of 8 MUg/ml, 16
      MUg/ml, and 32 MUg/ml, rAvBDs inhibited the growth of Staphylococcus aureus, E.
      coli, and Salmonella enterica serovar Typhimurium. While no synergistic
      inhibitory activity was found, a significant antagonistic effect was detected
      between rAvBD-2 and rAvBD-12. Treatment of E. coli and Salmonella Typhimurium
      with rAvBDs diminished their natural resistance to bile salts. Under the
      nonreplicating low-nutrient condition, rAvBDs at a concentration of 16 MUg/ml
      were able to kill E. coli and S. aureus within 30 min of contact. The
      antimicrobial activities of rAvBDs were enhanced by lowering salt concentration
      and pH from 7 to 6. The antimicrobial potency against S. aureus and E. coli could
      be characterized as rAvBD-6 > rAvBD-2 > rAvBD-12, which coincided with the net
      positive charges of these peptides. In conclusion, data from the current study
      warrant the investigation of the potential use of rAvBD-2, -6, and -12 as
      therapeutic and prophylactic antimicrobial agents against common bacterial
      pathogens.

PMID- 25618999
TI  - Molecular evolution of Marek's disease virus (MDV) field strains in a 40-year
      time period.
AB  - Marek's disease (MD) presents a serious threat in poultry production. The disease
      has been limited for over 40 yr by protective vaccination. The widely applied
      vaccination against MD is also one of the factors causing evolutionary pressure
      onto field Marek's disease virus (MDV) virulent strains. Molecular evolution of
      MDV genes involved in oncogenesis may increase the pathogenicity of MDV virulent
      strains. The goal of the presented study was to sum up the molecular evolution of
      MDV field strains isolated in the last 40 yr in Poland. In total, 85 field MDV
      strains collected between 1974 and 2012 were propagated in chicken embryo
      fibroblasts. After DNA extraction, three sets of primers were designed for PCR
      complementary to the MDV076 (RLORF7) region encoding the meq oncogene as well to
      the MDV077 (23 kDa protein binding alpha-enolase) and MDV077.5 (RLORF6) genes.
      The obtained 85 MDV076, 60 MDV077, and 58 MDV077.5 cloned fragments were
      sequenced and aligned with the sequences of reference MDV strains showing
      different pathogenicity levels. The retrieved nucleotide (nt) and deduced amino
      acid sequences of RLORF7, 23 kDa protein, and LORF6 of Polish field strains
      showed several mutations and substitutions homologous to those observed in
      reference strains with a determined pathogenicity. The observed changes indicated
      the continuous evolution of field MDV strains. The RLORF7 nt sequence of analyzed
      MDV isolates showed similarity to virulent and very virulent MDV reference
      strains. The obtained 23 kDa and LORF6 nt sequences provided more important data
      and were more similar to mildly pathogenic strains than to virulent and very
      virulent MDV. The specific nt motifs in all three genes may indicate an increase
      of MDV virulence and were found in strains starting from 2006. According to the
      obtained results, the strains isolated in 2012 are similar to the very virulent
      plus MDV group. The study showed that RLORF7, 23 kDa protein, and RLORF6
      fragments harbor sequence motifs that may have some association with MDV
      pathogenicity level. However, the exact role of the investigated regions in
      pathogenicity should be further examined by knock-out MDV strains. Also, the true
      MDV pathotype may only be determined by traditional in vivo experiments.

PMID- 25619000
TI  - Spatial and temporal epidemiology of infectious laryngotracheitis in central
      California: 2000-2012.
AB  - In October of 2005 an outbreak of a vaccine-like strain of infectious
      laryngotracheitis (ILT), indistinguishable from the chicken embryo origin (CEO)
      like vaccine strains, was detected by routine passive surveillance in the Central
      Valley of California, U. S. A. In response, a highly coordinated industry effort
      by two companies led to a significant decrease in the incidence of ILT over the
      same geographic region between 2008-2012. In order to understand the geographic
      and temporal spread of ILT in California before and after the outbreak, Global
      Information Systems (GIS) mapping coupled with spatial, temporal, and spatial-
      temporal statistics were used to identify retrospective and prospective low-rate
      clustering (i.e., less ILT than statistically expected) and high-rate clustering
      (i.e., more ILT than statistically expected) of ILT spatially and temporally.
      Results showed two high-rate retrospective spatial-temporal clusters and one low
      rate prospective spatial-temporal cluster which were all statistically
      significant (P < 0.05). Overall, spatial-temporal clustering accounted for 36.9%
      of the positive ILT cases, while temporal clustering and spatial clustering done
      separately each accounted for 0% of the ILT cases, respectively. This
      demonstrates the utility of combining spatial and temporal clustering for ILT
      surveillance. Due to the risk of reversion to virulence and spread to
      immunologically naive broilers, future application of the CEO-based vaccine in
      the identified high rate spatial-temporal clusters should be avoided and other
      vaccine alternatives considered in order to avoid repeat outbreaks in those
      areas. This should especially be followed during the winter months of December,
      January, and February, which were found to have the highest prevalence of ILT (P
      < 0.05). Analysis of GIS data within the high-rate clusters showed that wind
      direction and farm density were minor factors in the spread of ILT. Shared roads
      may have played a role in the spread of ILT in one of the two high rate spatial
      temporal clusters.

PMID- 25619001
TI  - A noncytolytic alpha toxin recombinant protein protects turkeys against
      Clostridium septicum challenge.
AB  - Clostridium septicum and its associated cytolytic alpha toxin, along with several
      other clostridial species, has been implicated as the causative agent of
      gangrenous dermatitis. A recombinant noncytolytic C. septicum alpha toxin (NCAT)
      peptide was developed for use as a vaccine and demonstrated to be safe at
      concentrations as high as 1 mg/ml. NCAT, used as a purified antigen, partially
      purified antigen, or in combination with native antigens, was compared to salt
      fractionated alpha toxin combined with denatured C septicum bacteria (native) in
      a vaccination trial. Three-day-old poults were placed into one of five groups and
      received two, 0.2-ml vaccinations 5 wk apart. Subcutaneous challenge with 3.2 x
      10(7) log phase C. septicum resulted in 78% to 95% of the vaccinated birds
      surviving challenge compared to 48% of sham-injected controls. By ELISA analysis
      on NCAT-coated plates, birds receiving vaccines containing the recombinant NCAT
      peptide showed significantly higher blood serum antibody concentrations than did
      birds receiving vaccines containing native antigens or alum controls.
      Additionally, high levels of maternally transferred antibodies reactive to NCAT
      purified antigens found in the pre-immune sera from naive 3-day-old poults
      suggest that the tertiary structure of the NCAT peptide has a high homology to
      the native protein structure. In conclusion, our study showed that the use of a
      vaccine comprised of a noncytolytic recombinant alpha toxin peptide antigen
      provided clinical protection equal to the use of vaccines formulated with
      inactivated native proteins at a reduced overall cost.

PMID- 25619002
TI  - Effects of vitamin D and yeast extract supplementation on turkey mortality and
      clostridial dermatitis incidence in a dexamethasone immunosuppression model.
AB  - Clostridial dermatitis (CD) is a production disease of commercial turkeys that is
      characterized by sudden mortality in market-aged male birds and by lesions that
      include fluid and air bubbles under the skin of the thigh, breast, and tail area.
      We have developed a model for CD using dexamethasone (Dex) injection that
      suggests this disease may be related to stressors during the last stages of
      turkey production. Male turkeys were provided with control feed and water or with
      feed supplemented with a commercial yeast extract (YE) product, water
      supplemented with vitamin D (VD), or the combination. At 6, 11, and 15 wk of age
      birds were treated with three intramuscular injections of Dex over a 5-day
      period. Both YE and VD, but not the combination, decreased early mortality. At
      week 7 mortality was increased by VD, and cellulitis lesions were seen in 7/8
      mortalities. Mortality at week 12 was decreased by both YE and the combination of
      YE and VD, and cellulitis lesions were seen in 8/17 mortalities. There were no
      significant differences in mortality at week 16. Total mortality was 66 birds,
      and 23 of these had cellulitis lesions (38%). There were no YE-treated birds with
      CD lesions; however, 67% of VD-treated birds had CD lesions. This study suggests
      that feed supplementation with YE may improve the ability of turkeys to withstand
      the stressors during late production and provide protection against the
      development of CD; however, high levels of VD supplementation may be detrimental.

PMID- 25619003
TI  - Effects of challenge with very virulent infectious bursal disease virus
      reassortants in commercial chickens.
AB  - Pathogenicity and immune responses were characterized in commercial broilers and
      layers challenged with very virulent infectious bursal disease virus (vvIBDV)
      reassortants (vvIBDV segment A + serotype 2 segment B and vvIBDV segment A +
      classic virulent segment B) at 7 days of age. In addition, functional
      immunosuppression was evaluated after challenge with infectious bronchitis virus
      (IBV) at 15 days of age. Layers showed higher levels and increased persistence of
      IBDV- and IBV-specific maternal antibodies than broilers at 1, 13, and 28 days of
      age. Cytokine gene expression was evaluated, after IBDV challenge, as an
      indicator of the innate immune function. Similar results were detected between
      the groups inoculated with vvIBDV reassortants. Interleukin-1beta (IL-1beta) in
      the bursa of layers demonstrated down-regulation at 1 day postinfection (DPI; 8
      days of age), and no changes at 4 DPI (11 days of age) compared with controls. In
      broilers, IL-6 expression in the bursa was down-regulated 1 DPI (8 days of age)
      and up-regulated at 4 DPI (11 days of age). A significant lymphoid depletion was
      detected at 21 DPI (28 days of age) in broilers exposed to a reassortant of
      vvIBDV segment A and classic virulent IBDV segment B. Finally, reduced specific
      antibodies against IBV measured 13 days after challenge were detected in layer
      and broiler chickens inoculated with a reassortant serotype 2 IBDV in segment B,
      suggesting functional immunosuppression. These results provide evidence
      indicating that current IBDV vaccination of breeders does not completely protect
      progeny chickens from challenge with reassortant vvIBDV.

PMID- 25619004
TI  - Comparison of diagnostic tools for the detection of aspergillosis in blood
      samples of experimentally infected falcons.
AB  - Antemortem diagnosis of avian aspergillosis is very challenging. Diagnostic
      assays using blood samples would aid in an early and more definitive diagnosis.
      In the current study, detection of anti-Aspergillus antibodies, Aspergillus
      antigen, and Aspergillus toxin (fumigaclavine A), protein electrophoresis and
      measurement of acute-phase protein concentrations were performed on serum of 18
      adult and plasma of 21 juvenile gyr-saker hybrid falcons (Falco rusticolus x
      Falco cherrug). Adult (n = 15) and juvenile (n = 18) falcons were experimentally
      inoculated with different dosages of the same strain of Aspergillus fumigatus and
      an additional three falcons from each age group were used as uninfected control
      animals. Blood samples were collected prior to inoculation and at 28 days
      postinoculation. Of the 33 inoculated falcons, 16 demonstrated clinical signs
      (vomiting, greenish urates, dyspnea, ruffled feathers) commonly associated with
      aspergillosis and in 14 falcons necropsy revealed aspergillosis granulomas
      confirmed by mycology and histopathology. Positive galactomannan results were
      rare, with only 3/15 positive samples from adult falcons and none in the juvenile
      birds. Most of the inoculated falcons showed an increase of serum amyloid A
      (66.7%) and haptoglobin (70.4%), but fumigaclavine A was not detected in the
      blood from any of the experimental animals. Elevated antibody indices were
      detected in 96.7% of the inoculated birds, but also in 66.7% of the controls.
      Significant decreases in albumin:globulin ratio were obvious in 81.5% of the
      inoculated birds, including 100% of the birds with granulomas. Blood from falcons
      with granulomas demonstrated significantly increased concentration values of
      alpha 2 and beta globulins, decreased percentages of prealbumin and albumin, and
      increased percentages of alpha 2 and beta globulins compared to inoculated
      falcons without granulomas. In conclusion, acute-phase proteins and the
      electrophoretic profile of birds challenged with A. fulmigatus show significant
      alterations, which in combination with other diagnostic procedures, assist in the
      early diagnosis of avian aspergillosis.

PMID- 25619005
TI  - Prevalence and distribution of avian influenza a(H5N1) virus clade variants in
      live bird markets of Vietnam, 2011-2013.
AB  - Active surveillance for avian influenza (Al) viruses in poultry sold at live bird
      markets (LBMs) was conducted in 44 of 63 provinces throughout Vietnam over two
      periods from September 2011 to February 2012 and October 2012 to June 2013. The
      study objectives were to assess the prevalence of avian influenza type A, H5, and
      H5N1 subtype viruses and characterize the geographical and temporal distribution
      of H5N1 virus genetic variants across the country. Monthly sampling was conducted
      in 394 LBMs located in 372 communes. A total of 9790 oropharyngeal swabs from
      poultry were screened for influenza A virus by real-time reverse-transcriptase
      PCR Virus isolation was attempted on all positive samples in embryonated chicken
      eggs, and the HA1 region of each H5 virus isolate was sequenced. Market
      prevalence of H5 subtype virus was 32.2% (127/394) over the cumulative 15 mo of
      surveillance. Phylogenetic analyses indicated that clade 1.1 viruses persisted in
      the south, whereas three genetically distinct subgroups of dade 2.3.2.1 were
      found simultaneously in northern, central, and southern Vietnam. Clade 2.3.2.1c
      viruses first appeared in July 2012 and spread rapidly to the center and south of
      Vietnam in late 2012, where they were predominant among clade 2.3.2.1 viruses and
      were detected in both active LBM surveillance and poultry outbreaks. Given the
      overlapping geographic distribution of dade variants and the antigenic divergence
      previously described for these dades, current AI poultry vaccines used in Vietnam
      may require bivalent formulations containing representatives of both dade 1.1 and
      dade 2.3.2.1 viruses.

PMID- 25619006
TI  - Antibody response and protective immunity of chickens vaccinated with booster
      dose of recombinant oil-adjuvanted Leucocytozoon caulleryi subunit vaccine.
AB  - Leucocytozoon caulleryi is an economically important poultry pathogen that causes
      subclinical to fatal disease in chickens. Because of limited preventive and
      treatment options against this disease, an oil-adjuvanted recombinant vaccine (O
      rR7) targeting the R7 protein of L. caulleryi second-generation schizonts was
      developed. Different vaccination programs, namely, single vaccination at 45 days
      (0.1-ml dose), single vaccination at 130 days (0.25 ml), and initial vaccination
      at 45 days (0.1 ml) followed by a booster dose at 130 days (0.25 ml) were
      explored to compare the effects of single and booster vaccination on antibody
      response, duration of protective immunity, and degree of clinical signs after
      experimental L. caulleryi infection. Of the three treatments groups, initial
      vaccination at 45 days followed by a booster vaccination at 130 days of age
      resulted to rapid increase in antibody titers, which persisted for up to 182
      days. Antibody titers reached peak values 35 days and 14 days after initial and
      booster vaccination, respectively. In comparison, single vaccination at 45 days
      of age resulted in production of antibodies above 1600 ELISA units for 56 days
      postvaccination, and single vaccination at 130 days of age produced peak antibody
      titers 35 days postvaccination, which remained above 1600 ELISA units for 126
      days. Experimental infection of L. caulleryi at 256 days, when antibody titers
      had waned, did not result to severe clinical disease in chickens that received
      booster vaccination, whereas mild to severe disease was observed in chickens that
      received a single vaccination. Evaluation of immune response at 15 and 21 days
      postinfection showed that chickens that received booster vaccination had a
      twofold increase (P < 0.01) in antibody titers as compared to those receiving a
      single vaccination. Administering booster shots of O-rR7 is therefore
      recommended, especially in farms located in areas where Leucocytozoon is endemic.

PMID- 25619007
TI  - Isolation and identification of Duck tembusu virus strain lH and development of
      latex-agglutination diagnostic method for rapid detection of antibodies.
AB  - SUMMARY. An outbreak of egg-drop syndrome occurred on a Sheldrake duck farm in
      Longhai in Fujian Province, China, in 2012. The main clinical symptoms were
      sharply reduced egg production, crooked necks, and death. We isolated the virus
      from the sick ducks, identified it, and observed the histopathologic changes
      after viral infection. We detected viral RNA in the blood and feces of the
      infected ducks and developed a latex-agglutination diagnostic method to detect
      anti-Tembusu-virus antibodies. Our results show that the pathogenic virus is a
      Tembusu virus. The histopathologic changes included follicular cell degeneration
      and necrosis, follicular cavity filled with blood cells, massive necrosis in the
      brain, and degeneration and necrosis of the nerve and glial cells. When the
      transmission of the virus in the infected ducks was studied, the duck blood was
      positive for viral nucleic acid for up to 29 days, and the feces were positive
      for viral nucleic acid for up to 13 days. We successfully established a simple,
      rapid, and easy- to-use latex-agglutination diagnostic method for the detection
      of antibodies against duck Tembusu virus.

PMID- 25619008
TI  - High seroprevalence of respiratory pathogens in hobby poultry.
AB  - Seroprevalence studies on respiratory pathogens have been done extensively in
      commercial laying hens, broilers, and, to a lesser extent, backyard poultry. In
      Europe, seroprevalence studies in backyard and fancy breed poultry flocks are
      scarce and limited to a few pathogens, such as Mycoplasma gallisepticum (MG);
      others, such as Ornithobacterium rhinotracheale (ORT), are missing. A commercial
      ELISA for detection of antibodies against six selected pathogens was performed on
      460 serum samples from chickens across Flanders. Anti-ORT antibodies were, by
      far, the most prevalent, with a prevalence of 95.4%. Infectious bronchitis virus,
      Mycoplasma synoviae, and avian metapneumovirus antibodies were found in 75.6%,
      76.3%, and 63.5% of the animals, respectively. Antibodies against MG and
      infectious laryngotracheitis virus were found in 36.7% and 30% of the animals,
      respectively. These data demonstrate the high seroprevalence of respiratory
      pathogens among hobby poultry; therefore, it is possible that this group could
      act as a reservoir for commercially kept poultry.

PMID- 25619009
TI  - Taqman real-time PCR assays for rapid detection of avian pathogenic Escherichia
      coli isolates.
AB  - Avian pathogenic Escherichia coli (APEC) isolates are currently differentiated
      from nonpathogenic strains by classical PCR of virulence genes. This study
      improves the detection of the five main virulence genes used for APEC detection
      with the development of duplex and single Taqman real-time PCR to these targets.
      Primers and probes targeted to ompT, hlyF, iroN, iutA, and iss genes were
      designed and used in the implementation of single (iss) and duplex (hlyF/ompT and
      iroN/iutA) Taqman PCR assays. All five virulence genes of E coli strains were
      successfully detected by classical and Taqman real-time (single and duplex) PCR.
      A panel of 111 E coli isolates, obtained from avian samples collected in
      different Brazilian regions between 2010 and 2011, were further tested by both
      assays. Complete agreement was observed in the detection of four genes, ompT,
      hlyF, iron, iutA, but not for iss. This issue was addressed by combining the
      forward primer of the classical PCR to the new iss reverse primer and probe,
      resulting in complete agreement for all five genes. In total, 61 (55%) Brazilian
      E. coli isolates were detected as APEC, and the remaining 50 (45%) as avian fecal
      E. coli (AFEC). In conclusion, classical and Taqman real-time PCR presented
      exactly the same analytical performance for the differentiation of APEC and AFEC
      isolates. The developed real-time Taqman PCR assays could be used for the
      detection and differentiation of APEC isolates.

PMID- 25619010
TI  - Phylogenetic and pathogenic analysis of a novel H6N2 avian influenza virus
      isolated from a green peafowl in a wildlife park.
AB  - H6 subtype avian influenza virus, which has been circulating among different
      species, causes considerable concern for both veterinary medicine and public
      health. We isolated a strain of H6N2 avian influenza virus from healthy green
      peafowl (Pavo muticus) in Qinghuangdao Wildlife Park in Hebei Province, China, in
      2012. A phylogenetic analysis indicated that the isolated H6N2 strain had the
      same gene constellation as southern China strains, which were predominantly
      isolated from waterfowl distributed in Shantou, Guangxi, and Hunan in 2001-2010.
      The isolate showed no and low pathogenicity in chickens and ducks, respectively.
      However, it replicated efficiently in the lungs and turbinate of infected mice,
      resulting in thickened alveolar septa and moderate interstitial pneumonia. This
      finding raises concerns that the H6N2 subtype maybe evolve into a novel endemic
      avian influenza virus. Therefore, periodical surveillance of avian influenza
      viruses must be undertaken to monitor the advent of novel viruses.

PMID- 25619011
TI  - Isolation of Actinobacillus pleuropneumoniae from layer hens showing clinical
      signs of infectious coryza.
AB  - Actinobacillus pleuropneumoniae is the causal agent of porcine pleuropneumonia,
      which is a highly contagious respiratory disease that affects swine nearly
      exclusively. An isolate with characteristics of some Pasteurellaceae family
      members (Gram-negative bacterium, pleomorphic, and NAD-dependent) was isolated
      from layer hens showing clinical signs of infectious coryza. This bacterium
      presented hemolysis on rabbit red blood cell agar plates, and PCR amplification
      and sequencing of its 16S rDNA gene indicated 99% identity with A.
      pleuropneumoniae serotypes 3 and 7. The presence of a putative apxIIA gene was
      also determined by PCR. A single, smooth colony of this bacterium inoculated in
      five, 7-day-old chicken embryos via the yolk sac route induced 100% mortality.
      However, inoculation into 10-wk-old, specific-pathogen-free chickens induced only
      light facial swelling, and reisolation of the inoculated bacterium was negative.

PMID- 25619012
TI  - Tribasic copper chloride toxicosis in commercial broiler chicks.
AB  - Two broiler chicken houses containing 17,500 chicks each experienced an extreme
      elevation in chick mortality beginning on day 3 after placement. Clinical signs
      observed upon farm visit included numerous small chicks for their age; depressed,
      lethargic, and comatose chicks; and chicks huddling near feed pans and under
      heaters. Necropsied chicks were markedly pale and had atrophy of the thymus and
      bursa, swollen and edematous proventriculus, erosions in the koilin and in the
      proventricular-ventricular junction, pale kidneys, and yellowish to brownish
      orange liver often with linear pale areas. The chicks had watery blood and
      hematocrits measured from 9.5% to 18%. Chicken infectious anemia was initially
      suspected based on the clinical signs and gross lesions. Histopathology revealed
      multifocal acute hepatic degeneration and necrosis with golden-brown pigment in
      the cytoplasm of hepatocytes and Kupffer cells, moderate to severe koilin
      degeneration and fragmentation, multifocal mild to moderate proventricular
      necrosis, mild to moderate necrosis and loss of enterocytes, blunting of small
      intestinal villi, lymphoid depletion in the thymus and bursa, erythrophagocytosis
      in the liver and spleen, and acute renal tubular degeneration and necrosis.
      Special stains revealed mild to abundant accumulation of copper pigment in the
      cytoplasm of hepatocytes and iron pigment in the cytoplasm of Kupffer cells. Feed
      analysis revealed 2140 to 2393 parts per million of copper in the starter ration,
      and heavy metal analysis detected markedly elevated copper levels in formalin
      fixed samples of the liver. Excessive amounts of tribasic copper chloride in the
      starter ration caused copper toxicosis in these chicks. Similar clinical signs
      and lesions were reproduced when the suspect feed was used in an experimental pen
      trial.

PMID- 25619013
TI  - Clostridium perfringens type A enteritis in blue and yellow macaw (Ara ararauna).
AB  - This study describes an outbreak of necrotic enteritis caused by Clostridium
      perfringens type A in captive macaws (Ara ararauna). Two psittacine birds
      presented a history of prostration and died 18 hr after manifestation of clinical
      signs. The necropsy findings and histopathologic lesions were indicative of
      necrotic enteritis. Microbiologic assays resulted in the growth of large gram
      positive bacilli that were identified as C. perfringens. PCR was used to identify
      clostridium toxinotypes and confirmed the identification of isolated strains as C
      pefringens type A, positive to gene codifying beta 2 toxin. The infection source
      and predisposing factors could not be ascertained.

PMID- 25619014
TI  - Enterococcus cecorum infection in a racing pigeon.
AB  - Until now, Enterococcus cecorum (EC) has been known as a pathogen for broilers,
      broiler breeders, and Pekin ducks. In the present report, we describe a fatal
      systemic EC infection in a young racing pigeon (Columba livia forma domestica).
      EC was isolated from the heart, liver, spleen, and intestine of the bird in pure
      culture. In the pathologic examination, the pigeon showed enteritis and an
      ulcerative gastritis, which may have been predisposing factors for the
      development of the generalized EC infection. An accumulation of gram-positive
      cocci in spleen tissue was found in the histopathologic examination and confirms
      the presence of a systemic EC infection in the pigeon. Additionally, EC was
      isolated from cloacal swabs of other pigeons in the same loft, but no additional
      pigeons were submitted for necropsy. All EC isolates tested were negative by PCR
      for the enterococcal virulence factors cytolysin, enterococcal surface protein,
      aggregation substance, hyaluronidase, and gelatinase. Therefore, the reason for
      the enhanced virulence of the EC isolate remains unknown. Our report confirms EC
      as a disease-causing agent in pigeons and presents the first data concerning the
      analysis of EC for virulence factors.

PMID- 25619015
TI  - Postvaccinal reovirus infection with high mortality in breeder chicks.
AB  - A broiler breeder flock was subcutaneously vaccinated at the hatchery with a live
      avian orthoreovirus (ARV) vaccine against viral arthritis. Chicks began to die at
      3 days of age and postmortem examination revealed massive subcutaneous
      hemorrhages and edema on the dorsal aspect of the neck at the site of
      vaccination, a severe necrotic hepatitis, and pulmonary edema. Microscopically,
      the main lesion was a multifocal vacuolar degeneration and necrosis of randomly
      distributed small groups of hepatocytes with presence of apoptotic and
      multinucleated syncytial cells. Necrotic foci were also found in the lungs as
      well as a hemorrhagic, granulomatous, and heterophilic cellulitis and myositis of
      the neck and a generalized depletion and lymphocytolysis of lymphoid organs. At 8
      days of age, birds also began to show hock swelling histologically characterized
      by a fibrinoleucocytic inflammation of the articulation and tendon sheaths, with
      hyperplasia of the synovial membrane, and lymphoplasmocytic infiltration. PCR and
      viral culture of livers were positive for ARV. Partial sequencing of the S1 gene
      from the virus isolate showed 99.2% to 99.8% homology with three vaccinal strains
      (ARV S1133, 1733, and 2408). Viral particles compatible with reovirus virions
      were observed at transmission electron microscopy. Investigation at the hatchery
      revealed that chicks were inadvertently administered an S1133 reovirus vaccine
      labeled for water administration in 10- to 17-week-old chickens. This human error
      is most likely the reason for this unusually severe viremic reovirus infection
      that affected this flock at such an early age.

PMID- 25619016
TI  - Occurrence of avian botulism in Korea during the period from June to September
      2012.
AB  - Botulism is a paralytic disease caused by the botulinum neurotoxin produced by
      Clostridium botulinum. In the summer season in Korea, intensive outbreaks of
      avian botulism were reported in both poultry and wild birds, including five
      Korean native chicken farms (HanHyup NO.3), one pheasant (Phasianus colchicus
      karpowi) farm, and one community of spot-billed ducks (Anas poecilorhyncha). The
      affected domestic birds showed 24.5% to 58.3% mortality, with specific clinical
      signs including ataxia, limber neck, and diarrhea. To confirm the botulinum
      toxin, neutralization tests were performed on sera (four Korean native chicken
      farms and one pheasant farm) or culture supernatant (spot-billed ducks).
      Additionally, the contents of the cecum and liver from poultry presenting signs
      suggestive of botulism were inoculated to isolate the pathogen. The toxin genes
      were then detected by polymerase chain reaction (PCR). Through the neutralization
      tests, it was possible to diagnose the botulism and, except in the case of one
      Korean native chicken farm, to identify the type of pathogen. Using detection by
      PCR, except in two cases of the Korean native chicken farms, the botulinum toxin
      gene was found. Additionally, in four cases, it was possible to identify the C/D
      mosaic type using PCR. This paper reports the first occurrence of avian botulism
      in domestic birds and the first detection of botulism caused by this mosaic type
      in Korea.

PMID- 25619017
TI  - Nursing professionalism.

PMID- 25619018
TI  - DATA BITS. What is a fall safety agreement and does it work?

PMID- 25619020
TI  - Prestigious recognition for environmental health professionals.

PMID- 25619019
TI  - Nurses play valuable roles in diabetes multidisciplinary team caring for children
      with diabetes in Louisville, Kentucky.

PMID- 25619021
TI  - Consuming untreated water in four southwestern Alaska Native communities: reasons
      revealed and recommendations for change.
AB  - In this article, the authors provide the first in-depth account of why some
      Alaska Native people drink untreated water when treated water is available. Their
      qualitative research was conducted in four Alaska Native village communities that
      have treated water available from a centralized distribution point. Most
      respondents (n = 172; 82%) reported that some of their household's drinking water
      came from an untreated source. Motives for drinking untreated water emerged from
      analysis of open-ended questions about drinking water practice and could be
      categorized into six themes: chemicals, taste, health, access, tradition, and
      cost. Importantly, some residents reported consuming untreated water because they
      both liked untreated water and disliked treated water. As such, interventions to
      increase safe water consumption should address this dichotomy by providing
      education about the benefits of treated water alongside the risks involved with
      drinking untreated water. Based on the findings, the authors provide specific
      recommendations for developing behavior change interventions that address
      influences at multiple social-ecological levels.

PMID- 25619022
TI  - Biomonitoring for perfluorochemicals in a Minnesota community with known drinking
      water contamination.
AB  - Perfluorochemicals (PFCs) are pervasive and persistent environmental contaminants
      with uncertain public health implications. Following the discovery of PFC
      contamination in public and private drinking water supplies in Washington County,
      Minnesota, the authors conducted a pilot biomonitoring study. Serum samples from
      196 residents of two communities were analyzed for seven PFCs. Perfluorooctanoic
      acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexanesulfonate
      (PFHxS) were detected in all serum samples collected. Perfluorobutanoic acid
      (PFBA) and perfluorobutane sulfonate (PFBS) were found in 28% and 3% of the
      samples, respectively. The geometric mean for PFOA was 15.4 ng/mL (range: 1.6-177
      ng/mL), PFOS was 35.9 ng/mL (range: 3.2-448 ng/mL), and PFHxS was 8.4 ng/mL
      (range 0.32-316 ng/mL). Mean levels for PFOA, PFOS, and PFHxS were higher in
      males and increased with age. Mean PFC serum levels for three PFCs were
      significantly elevated when compared to levels found in the U.S. population.

PMID- 25619023
TI  - Communicating about biomonitoring and the results of a community-based project: a
      case study on one state's experience.
AB  - Communicating biomonitoring results is a challenge. This article describes the
      communication strategies used by the Minnesota Department of Health (MDH) to
      support a biomonitoring project in communities exposed to perfluorochemicals
      through contamination of their drinking water. Using archival documents, media
      reports, and informant interviews, the case study described here elucidates MDH's
      successes, challenges, and lessons learned with communicating biomonitoring
      results characterized by uncertainty about health effects and risk levels. MDH's
      communication approach focused on engaging audiences and repeating key messages.
      Despite the repeated message that the biomonitoring project was an exposure study
      and not a health study, lay audiences generally expressed lingering discontent
      with the results while others expressed satisfaction and understanding. This
      outcome highlights the importance of implementing carefully developed
      communication plans with well-defined goals, objectives, and intended audiences,
      and with evaluation guiding the entire process.

PMID- 25619024
TI  - The environmental health workforce in the 21st century.

PMID- 25619025
TI  - The first edition of the Model Aquatic Health Code is now available: what's next?

PMID- 25619027
TI  - The great barrier backlash.

PMID- 25619026
TI  - Disease detective applies skills to surveillance evaluation.

PMID- 25619028
TI  - In memoriam Joe Beck.

PMID- 25619029
TI  - New Year's resolution: get to know Chikungunya.

PMID- 25619030
TI  - Hazardous metals in vintage plastic toys measured by a handheld X-ray
      fluorescence spectrometer.
AB  - Over 100 plastic toys from the 1970s and 1980s, both polyvinyl chloride ("vinyl")
      and nonvinyl, were analyzed in the study described here using a handheld X-ray
      fluorescence spectrometer to quantify hazardous metal content. A sampling of
      recent vinyl toys was also tested. The majority of nonvinyl samples were Fisher
      Price brand toys. The vinyl toys consisted largely of Barbie dolls and other
      dolls. Overall, lead or cadmium was found in 67% of vintage plastic toys,
      frequently at concentrations exceeding current U.S. and European limits. Arsenic
      was detected at levels of concern in 16% of the samples. In the nonvinyl toys,
      heavy metal content was found to correlate with certain colors of plastic. The
      likely sources of the detected metals are discussed. None of the contemporary
      vinyl toys contained detectable cadmium, lead, or arsenic. Given that vintage
      toys remain in widespread use by children in homes and other locations, the
      results illuminate a potential source of heavy metal exposure for children.

PMID- 25619031
TI  - Florida county health department, environmental health 2006 survey: do rural
      counties know "what to do' in a chemical or all-hazards event?
AB  - The objective of the study described here was to determine basic plans and
      collaboration with first responder stakeholders and to identify perceived roles
      and responsibilities in preparing for and responding to a chemical disaster. A
      survey was developed and provided to environmental health personnel at county
      health departments (CHDs) in Florida. Most of the counties had good collaborative
      relationships with first responder stakeholders. A little more than half of the
      respondents had access to a resource manual with contact information and had
      developed and maintained a chemical plan. Rural counties were less likely to know
      "what to do" or their responsibility in a chemical disaster; however, both rural
      and nonrural counties were equally likely not to have a written plan. Public
      health agencies at the local CHD must be the communicators of public health
      messages in coordination with the incident commander and the state communications
      office in a chemical disaster, so it is important to strengthen collaboration and
      cooperation with chemical response stakeholders.

PMID- 25619032
TI  - Bisphenol A: a threat to human health?
AB  - All of us now carry in our bodily tissues a virtual stew of heavy metals and
      hundreds of synthetic chemicals: persistent ones, which can have a "half-life" in
      the body of several years; and nonpersistent compounds, which may pass through
      the body in a matter of hours. Bisphenol A (BPA) is a nonpersistent compound that
      can alter the reproductive system of laboratory animals even at extremely low
      exposure levels. This is relevant because BPA is chronically present in our
      environment with the potential for constant exposure, making it functionally
      equivalent to a persistent compound. In this review the authors emphasize
      particular outcomes that occur in response to the relevant dose of BPA exposure
      that causes developmental effects on reproductive systems, brain and metabolic
      processes, and the male germ line. At a specific dose level, BPA exposure also
      shows oxidative toxicity and carcinogenic effects.

PMID- 25619034
TI  - A study of the antimicrobial resistance and transfer of resistance among
      organisms isolated from lettuce (Lactuca sativa) leaves in three localities in
      southwest Nigeria.
AB  - The bacterial flora of lettuce from western Nigeria were investigated for their
      identity, antimicrobial resistance, and ability to transfer such resistance to
      other organisms. The isolated contaminants were mostly Gram-negative organisms of
      the Enterobacteriaceae family, which included Enterobacter species and E. coli.
      The organisms were resistant to a wide range of antimicrobials and they exhibited
      multiple antimicrobial resistance phenotypes. Common resistance phenotypes
      observed included those to beta lactam antibiotics, trimethoprim, and
      streptomycin. A majority of the isolates had minimum inhibitory concentration of
      trimethoprim over 1,000 mg/L and they were shown to possess the ability to
      transfer their resistance to a plasmidless E. coli strain. The results of the
      authors' study underscore the contributory role of lettuce in the dissemination
      of antimicrobial resistance in the Nigerian community.

PMID- 25619033
TI  - Comparative study of heavy metals in "soil-wheat" systems between sewage
      irrigated areas and clean-water-irrigated areas in suburban Beijing.
AB  - After years of irrigating farmland with wastewater, concern is increasing about
      health risks from heavy metals contaminating wheat grown in sewage-irrigated
      soils in suburban areas of Beijing, China. The study discussed in this article
      aimed to compare the characteristics of heavy metal distribution in a sewage
      irrigated "soil-wheat" system with those from a clean-water-irrigated area by
      collecting and analyzing samples from both areas. The results indicated that the
      average concentrations of copper, chromium, lead, and zinc in sewage-irrigated
      soil were higher than the values in the clean-water-irrigated region. Irrigation
      with wastewater could lead to increased bioconcentration factors. Therefore,
      issues of food contamination caused by sewage irrigation deserve more attention.

PMID- 25619036
TI  - Hand washing among Palestinians in the West Bank and Gaza Strip: attitudes and
      practices.
AB  - Regular and proper hand washing is a low-cost and effective intervention to
      prevent the spread of infectious diseases. The authors' study aimed to assess the
      socioeconomic and demographic characteristics associated with attitudes and
      practices of hand washing before eating in the West Bank and Gaza Strip. It also
      assessed parents' participation in the personal hygiene of their children.
      Results revealed that almost all participants believed that it is always
      necessary to wash one's hands before eating. Females had higher rates than males
      for washing hands before eating as well as for helping with child hygiene. Not
      surprisingly, a positive relationship existed between educational level and
      attitudes and practice of washing hands before eating. The authors recommend that
      governments, ministries, and different nongovernmental organizations have an
      active role in developing and implementing programs in order to improve the
      health of their communities. Such programs should be conducted in all localities
      and at all levels including homes, schools, and public domains.

PMID- 25619035
TI  - A study on exposure to cyanide among a community living near a gold mine in
      Malaysia.
AB  - Cyanidation in gold extraction has detrimental impacts on the ecosystem and the
      population in surrounding areas. The research described in this article aimed to
      assess the health effects of environmental exposure to cyanide in a community
      near a gold mining area in Malaysia. A total of 255 members of the exposed
      community and 117 members of the control community answered questionnaires on
      their exposure to a gold mine and health outcomes. Urine samples were collected
      for biomarker assessment (i.e., urinary thiocyanate). The authors found that the
      mean level of urinary thiocyanate was significantly higher among the exposed
      community (0.30 +/- 0.26 mg/dL) than the control community (0.24 +/- 0.23 mg/dL)
      (p = .0021). The exposed community had a significantly higher prevalence of
      headaches (prevalence odds ratio [pOR] = 2.6, p = .001), dizziness (pOR = 3.7, p
      < .001), skin irritation (pOR = 2.1, p = .040), and eye irritation (pOR = 5.1, p
      = .004). No association occurred between dietary exposure and urinary biomarkers.
      Smokers living near a gold mine had a higher urinary thiocyanate level (0.56
      mg/dL) than smokers in the control community (0.49 mg/dL).

PMID- 25619037
TI  - Isolation of Legionella pneumophila from cooling towers, public baths, hospitals,
      and fountains in Seoul, Korea, from 2010 to 2012.
AB  - Legionnaire's disease is associated with a high mortality rate. The authors
      collected 3,495 water samples in Seoul, Korea, between 2010 and 2012 from public
      facilities (cooling towers, public baths, hospitals, and decorative fountains),
      which are considered the major habitats of Legionella pneumophila. In all, 527
      (15.1%) isolates of L. pneumophila were obtained by microbial culture and
      polymerase chain reaction. Serological diagnosis and pulsed-field gel
      electrophoresis (PFGE) analysis were performed for the samples. The authors
      categorized the samples into four groups (A-D) on the basis of PFGE results. The
      analysis revealed that cooling towers containing the most samples with L.
      pneumophila serogroup 1 constituted the highest proportion of isolate. Samples
      from public facilities and serogroups could be distinctively classified by PFGE
      patterns. Thus, it is expected that source-specific features revealed through
      PFGE and serological analyses could serve as the basis for effectively coping
      with future outbreaks of L. pneumophila.

PMID- 25619038
TI  - Association between PM10 and respiratory hospital admissions in different seasons
      in heavily polluted Lanzhou City.
AB  - Exposure-response relationship between particulate matter less than 10 MUm in
      diameter (PM10) and human health in different seasons from 2001 to 2005 was
      examined based on hospital admissions data of respiratory system diseases from
      four major hospitals in Lanzhou, China. To quantify associations of respiratory
      system diseases with multiple air pollutants and meteorological conditions, a
      semiparametric generalized additive model was used in the authors' study by
      implementing daily ambient sulfur dioxide, nitrogen dioxide, and PM10 data
      collected from the Lanzhou Environmental Monitoring Station and daily
      meteorological data from Lanzhou Meteorological Bureau. Results showed that daily
      averaged PM10 increased per interquartile range the hospital admissions number of
      respiratory diseases by 3.3% in spring, 1.4% in summer, 3.6% in autumn, and 4.0%
      in winter from a single-pollutant model, or 3.1%, 1.4%, 3.0%, and 4.0% from a
      multi-pollutant model, respectively. The effect of PM10 on respiratory hospital
      admissions was lowest in summer and highest in winter. The relative risks of PM10
      on female or the elderly (>= 65 yrs.) were higher, showing a stronger association
      of PM10 with respiratory diseases in female and elderly groups than in males and
      people younger than 65.

PMID- 25619039
TI  - Boys, not girls, are negatively affected on cognitive tasks by lead exposure: a
      pilot study.
AB  - The study described in this article provides behavioral evidence that boys
      experience the deleterious cognitive effects of lead more than girls do. In fact,
      girls with elevated blood lead levels (BLLs - 10 MUg/dL) performed as well as
      girls without elevated BLLs on behavioral measures of cognition. This was shown
      by testing executive function and reading readiness skills of 40 young children
      (aged three to six years; 23 with elevated blood lead levels, 17 without)
      residing within a U.S. Environmental Protection Agency-designated lead Superfund
      site. The results also indicate that elevated BLLs are related to a more
      pronounced negative impact on executive function than on reading readiness. These
      findings support recent research on adults indicating that lead exposure is
      related to atrophy within the prefrontal cortex and other work suggesting that
      estrogen and estradiol may act as neuroprotectants against the negative impact of
      neurotoxins.

PMID- 25619040
TI  - Evaluation of HACCP system implementation on the quality of mixed fresh-cut salad
      prepared in a university canteen: a case study.
AB  - The increasing awareness that foods can represent vehicles for health risk
      factors has caused scientists and public authorities to multiply their efforts to
      reduce these risks to within acceptable limits. Nevertheless, some challenging
      issues still remain unsolved and new ones have recently emerged, such as the
      increase in outbreaks of foodborne diseases originating from the consumption of
      meals at catering facilities. The study described in this article was aimed at
      evaluating the microbiological quality of mixed fresh-cut salads at an Italian
      university canteen operating in conformity with the hazard analysis and critical
      control point (HACCP) system. The effectiveness of the preventive and corrective
      measures taken was also assessed with respect to the frequency of unsatisfactory
      salad samples. During the investigation, E. coli, Salmonella spp., and Listeria
      monocytogenes were never detected. By contrast, a high number of samples exceeded
      the mandatory or suggested limits for food processing hygiene (in terms of
      mesophilic aerobes, coliforms, Staphylococcus aureus, Bacillus cereus, and
      sulfite-reducing clostridia counts). Despite the introduction of a series of
      preventive and corrective actions, the results were only partially satisfactory;
      this was most likely due to the impossibility of having available an adequate
      level of human resources that are indispensable to correctly putting the HACCP
      procedures into daily practice.

PMID- 25619041
TI  - Geostatistical analysis of the relationship between heavy metals in drinking
      water and cancer incidence in residential areas in the Black Sea region of
      Turkey.
AB  - In the study described in this article, the authors examined the relationship
      between heavy metals in the drinking water and cancer densities in residential
      areas. The Turkish cities of Trabzon, Rize, and Giresun in the eastern Black Sea
      region were chosen as the study areas. Cancer registry data, population
      information, heavy metal chemical analysis results for drinking water, and other
      spatial information for the region were collected in a database designed in GIS.
      Information on a total of 13,012 registered cancer cases from the years 2000-2007
      was obtained from a cancer record center and depicted spatially on a map. The
      incidence values explaining cancer density in residential units were calculated.
      Chemical analyses were then conducted to determine the presence of 17 different
      heavy metals by collecting a total of 541 drinking water samples. It was
      determined that among the 17 analyzed heavy metals, beryllium, nickel, antimony,
      and molybdenum had a significant relationship with cancer incidence values in the
      residential units.

PMID- 25619042
TI  - Needs assessment survey for Master's of Science training in environmental health
      science in Swaziland.
AB  - A needs assessment survey research was carried out for Master's of Science
      training in environmental health in Swaziland. The objective of the survey was to
      acquire information on training needs, gaps, options of specializations, program
      structure, courses, topics, and research areas that are relevant to the needs of
      the stakeholders and sector organizations related to environmental health. A
      document study, focus group discussion with key informants, stakeholder forum
      workshop, and needs assessment questionnaire to the wider stakeholders were used
      for the study described here. The findings of the authors' study point to a
      shortage of qualified personnel in environmental health; lack of capacity in
      strategy planning and project management; and lack of capacity in research, data
      collection, and environmental monitoring skills, among other things. A program
      structure that takes into account the multidisciplinary nature of environmental
      health with provisions for specialization was favored. Suggestions on course
      content, mode of delivery, and research topics to be addressed were also given.

PMID- 25619043
TI  - GIS builds capacity to reclaim brownfields and respond to public requests:
      Elkhart County, Indiana.

PMID- 25619044
TI  - The road towards environmental justice from a multifaceted lens.

PMID- 25619045
TI  - [Intra-articular use of sodium hyaluronate (2,2,-2,7 MDa) in the treatment of
      Moroccan patients with knee osteoarthritis: randomized controlled trial].
AB  - OBJECTIVE: To assess the efficacy of intra-articular sodium hyaluronate,
      administred once weekly for 3 weeks (3 injections) in Moroccan patients with knee
      osteoarthritis over 6-month period. MATERIAL AND METHODS: We prospectively
      studied the outcome of 75 patients with painful knee osteoarthritis in grade 1, 2
      and 3 on ACR radiological criteria in our rheumatology clinic in Morocco. Group
      1: 45 patients were treated with 3-weekly injections of intra-articular sodium
      hyaluronate (1%; 2,2-2,7 MDa). Group 2 : 30 patients treated with symptomatic
      slow-acting drugs for osteoarthritis (SYSADOA). The efficacy parameters were
      Visual Analogue Scale (VAS) and Lequesne index. RESULTS: In group 1: 35/45 were
      female, a mean age of patients was 57.2 (+/- 8.2) years, and a mean Body Mass
      Index (BMI) was 28 (+/- 1.4) kg/m2. In group 2: 23/30 were female, a mean age of
      patients was 58.6 (+/- 2.8) years, and a mean of BMI was 27.8 (+/- 1.4) kg/m2.
      Before treatment in group 1, the mean of VAS was 6.5 cm (+/- 1), and of Lequesne
      index 10.5 (+/- 2.1). At 3 and 6 months after the third injection of sodium
      hyaluronate, there was a significant improvement from baseline of Lequesne index
      and VAS (P = 0.001). In group 2 before treatment, the mean of VAS was 7 cm (+/-
      0,7), and of Lequesne index 8 (+ 1.1), but the improvement from baseline at 3 and
      6 months of treatment was lower than group 1. CONCLUSION: The results of this
      prospective study, showed the efficacy of 3-weekly injections of sodium
      hyaluronate in the treatment of knee osteoarthritis in Moroccan patients over a 6
      month period.

PMID- 25619046
TI  - [Analysis of health policies to prevent non communicable diseases in the Wallonie
      Brussels Federation].
AB  - Because of their high prevalence and constant increase, and their impact in terms
      of human and financial costs, non-communicable diseases (NCD) represent an
      important public health issue. Recognizing this alarming situation, the
      international Community took decisive commitments to reduce the spread of this
      epidemic of the 21st century. These commitments have been translated in the
      national prevention and care policies. In the Wallonie-Brussels Federation (WBF),
      a set of health policies to prevent non communicable diseases was initiated. The
      objectives of the study were to describe, explore promotion and primary and
      secondary prevention against NCDs policies in WBF, to highlight the main
      challenges and issues, and to provide some recommendations to concerned actors.
      To achieve the objectives of this study, a literature review and a qualitative
      approach were used. Semi-structured interviews of key stakeholders were conducted
      in WBF. It involved 14 actors selected for their involvement in the formulation
      and implementation of these policies. It appears that the Belgian institutional
      complexity, the lack of willingness of policymakers in prevention and health
      promotion, the lack of a comprehensive structured policy of prevention and health
      promotion and an absence of any coordination structure are the main obstacles
      facing the formulation and implementation of these policies.

PMID- 25619047
TI  - [BOUGE-fitness test battery: health-related field-based fitness tests assessment
      in children and adolescents].
AB  - Physical fitness is an important determinant of global health in children and
      adolescents. Key components of physical fitness include cardiorespiratory
      fitness, flexibility, speed, and muscular and endurance strength. The school
      environment provides a great opportunity to assess the physical fitness level in
      children and adolescents. The french national program "Bouge... Une priorite pour
      ta sante! "(Move ... A priority for your health!) aims to assess the physical
      fitness of children and adolescents aged 6 to 18 years old in French schools. The
      aim of this paper is to describe the interest to assess different health-related
      physical fitness components. It presents the chosen tests within said battery for
      children and adolescents and explains how the battery was conceived. The health
      related physical fitness tests included in "BOUGE" were chosen for their
      validity, reliability, low cost and feasibility for all schools.

PMID- 25619048
TI  - [Simulation training in the management of obstetric emergencies. A review of the
      literature].
AB  - To assess the value of simulation based training in the management of obstetric
      emergencies. METHOD: A search by keywords: obstetrics, gynecology, simulation,
      drills, emergency training restricted to randomized trials led to a selection of
      eight articles. RESULTS: Shoulder dystocia simulation unmasked deficiencies in
      performing Mc Robert maneuver in nearly 20% of doctors in training as well as
      ineffective and potentially harmful maneuver such as pressure on the uterine
      fundus. Delivery of the impacted shoulder improved from 42.9% to 83.3% after
      simulation training leading to a shorter head to body delivery interval. In
      postpartum haemorrhage simulation, lack of knowledge on prostaglandins and
      alkaloids of ergot, delay to transfer the patient to the operating room (82% of
      cases) and a poor communication between different professionals were identified.
      Post simulation improvement was seen in knowledge, technical skills, team spirit
      and structured communication. In severe preeclampsia simulation, mistakes such as
      injection of undiluted magnesium sulphate, caesarean section on an unstable
      patient were identified and reduced by 75%. Management of magnesium sulphate
      toxicity was also improved after simulation training. CONCLUSION: This review
      confirms the potential of simulation in training health professionals on
      management of obstetrics emergencies. Although the integration of this training
      modality into the curriculum of health care professionals in obstetrics and
      gynaecology seems beneficial, questions on the cost, the minimum standard of
      facilities, type of mannequins, human resources and frequency of drills required
      to achieve the learning objectives remain unanswered.

PMID- 25619049
TI  - [Cardiac metastase of a soft tissue sarcoma: a case report and a review of the
      literature].
AB  - Soft tissue sarcomas represent rare tumors. They recur most often locally and in
      the lungs. We report the case of a 58-year woman who was treated for awith
      chemotherapy and then surgery. About a year after the end of the treatment an
      intracardiac mass was identified during a follow up chest CT-scan. The patient
      underwent a surgical resection of that mass found to bel myxoid chondrosarcoma
      metastasis. Only 2 cases of cardiac dissemination of extraskeletal myxoid
      chondrosarcoma have been described. The differential diagnosis of intracardiac
      masses is discussed. In some carefully selected cases atrisks of obstructive
      shock or embolization and unique metastatic location, cardiac surgery should be
      considered.

PMID- 25619050
TI  - [Rare complication of a late abortion: a case report].
AB  - We report the case of a young woman who presented with acute abdomen at our
      hospital. The control revealed the presence of fetal parts in extra-uterin and
      intra-abdominal place after a late abortion. The patient was succesfully operated
      by celioscopy.

PMID- 25619051
TI  - [The teaching of anatomy in Brussels before the founding of the Universite libre
      de Bruxelles].
AB  - Between 1733 and 1788, a "College of Medicine" assured the training of the
      students of Brussels. The lessons of anatomy were successively given by Adrien
      Charles Joseph Van Rossum, Paul Ignace De Bavay and Francois Du Rondeau. From
      1788 and until 1797, the Faculty of Medicine of the University of Louvain was
      displaced in Brussels, and the anatomical lessons were given by Pierre Corneille
      de Brabant. Under French domination, the College and the University were closed,
      and replaced with a School of Surgery, which became Medical School under Dutch
      regime. Anatomy was taught by Jean-Baptiste Terrade, Francois Antoine Curtet,
      then Pierre-Joseph Graux, who became the first professor of anatomy of ULB when
      the young university absorbed the school during its foundation.

PMID- 25619052
TI  - [15th annual workshop of thoracic oncology (JAOT)].

PMID- 25619054
TI  - Contribute to making things better.

PMID- 25619055
TI  - 'Troubled Families' scheme extended to under-fives.

PMID- 25619053
TI  - [ A welcomed low TSH].

PMID- 25619056
TI  - Earlier screening for life-threatening conditions in babies.

PMID- 25619057
TI  - Tooth brushing advice 'unacceptably inconsistent'.

PMID- 25619059
TI  - Parents burn, bleach and shave hair to 'treat' head lice at home.

PMID- 25619058
TI  - Older low-risk mums likely to need emergency support.

PMID- 25619060
TI  - Community pharmacies have a 'vital role' in public health.

PMID- 25619061
TI  - NMC consults on fee instalment plan.

PMID- 25619062
TI  - What does the new SEN code of practice mean for health visitors and school
      nurses?

PMID- 25619063
TI  - Preventing a child maltreatment epidemic.

PMID- 25619064
TI  - More than just the 'baby blues.

PMID- 25619065
TI  - School nurse 121 campaign.

PMID- 25619066
TI  - Delivery of CBT to treat postnatal depression: health visitors' perceptions.
AB  - The most extensively researched form of psychotherapy over the last 10 years,
      cognitive behavioural therapy (CBT), has recently been promoted in health
      visiting practice. Health visitors, frontline practitioners for the majority of
      women with postnatal depression (PND), stand between the use of antidepressants
      for PND on the one hand where compliance is not good and the potential to offer a
      practical alternative using cognitive behavioural techniques on the other. The
      aim of this study was to examine how health visitors understand the concept of
      CBT and envisage its implementation in practice with regard to the treatment and
      management of PND. A qualitative research methodology using a phenomenological
      approach was adopted to analyse transcripts from two semi-structured focus group
      interviews with nine health visitors about their work with PND and CBT. The
      findings demonstrated that health visitors do not want to be known as 'frontline'
      professionals in the delivery of CBT to treat PND as this would imply
      'counsellor'--a diversion from their professional identity and unique role.
      However, they wanted to be equipped with more than just introductory basic
      assessment and treatment techniques in CBT to deliver a pragmatic, psycho
      educational approach to PND in four to eight home sessions.

PMID- 25619067
TI  - Is there a need for placement evaluations for specialist practice students? A
      proposal.
AB  - This paper outlines a recent proposal justifying the initiation of standardised
      placement evaluations across specialist community public health nursing and
      specialist community nursing students while they undertake their educational
      programme. Within one approved education institute (AEI) it was identified that
      there was no standardised tool currently being used across the West Midlands,
      making the process of quality assurance extremely difficult. A clear rationale is
      provided for the use of such a tool, including supporting evidence from
      professional, statutory and regulatory bodies, health and education policies and
      quality assurance agencies. Placement evaluations are critical to students'
      learning, ensuring a safe and conducive environment, while providing a continuous
      cyclical process in conjunction with educational audits to allow the opportunity
      of regular assessment of the learning environment conforming to the Nursing
      Midwifery Council's risk-based approach. In light of the recent recommendations
      from the Francis report, it is pivotal that organisations such as the NHS and
      AEIs engage proactively together, fostering an open and transparent relationship
      to ensure standards of care are of the highest quality. Aspects of leadership
      theory are also discussed to enable the planned change to be successful.

PMID- 25619068
TI  - The process of consultation to a health visiting team based on the Solihull
      Approach: a critical reflection.
AB  - This paper aims to provide a critical reflection of the process of consultation
      offered by a child and adolescent mental health service (CAMHS) to a health
      visiting team. The consultation process followed two days of training in the
      Solihull Approach and took place over five 90-minute sessions at six-weekly
      intervals. In this paper, the Solihull Approach is used as a framework for
      understanding the consultation process, and the concepts of containment and
      reciprocity are explored within this context. The challenges and successes of the
      process are shared and the importance of providing a containing space for
      frontline practitioners is highlighted.

PMID- 25619069
TI  - Operation Smile: screening for birth defects.

PMID- 25619070
TI  - Keep calm and get yourself heard: Unite/CPHVA Student HV Question Time.

PMID- 25619071
TI  - Improving care for people with dementia in Devon.

PMID- 25619072
TI  - A clear message: delivering public health advice.

PMID- 25619073
TI  - [We are all participants in quality care!].

PMID- 25619074
TI  - [An historical mobilization of professionals].

PMID- 25619075
TI  - [Modifications of nursing student evaluation].

PMID- 25619076
TI  - [New pricing for infusions].

PMID- 25619077
TI  - [Authority given to nurses to discuss blood donation].

PMID- 25619079
TI  - [Healthcare law, bills of the Ministry of Health].

PMID- 25619078
TI  - [The cost of Prado in the hot seat].

PMID- 25619080
TI  - [A smoking cessation program].

PMID- 25619081
TI  - [A future institute for public health prevention, monitoring and intervention].

PMID- 25619082
TI  - [Digital territory project].

PMID- 25619083
TI  - [Nurse-patient relations in question].

PMID- 25619084
TI  - [A new translation of NANDA, Nursing Outcomes Classification, and Nursing
      Interventions Classification].

PMID- 25619085
TI  - [Medication advice from the Ministry of Health].

PMID- 25619087
TI  - [Obesity and cancer].

PMID- 25619086
TI  - [Chronic obstructive pulmonary disease, three suggestions by the Ministry of
      Health].

PMID- 25619088
TI  - [900,000 people are suffering from Alzheimer disease in France].

PMID- 25619089
TI  - [Access to care for vulnerable populations].
AB  - Accessing hospital care is a privilege for a growing proportion of the population
      in situations of economic and social precarity. It is therefore important that
      caregivers understand these difficulties in order to adapt their nursing
      approach.

PMID- 25619090
TI  - [The secondary nurse manager; a strategic role in the evolution of clinical
      practices].
AB  - Nurse clinicians still rarely base their practices on scientific knowledge.
      However, in order for them to be actively engaged in practice change, they must
      have constant and effective support from key players of trust within the
      organisation.

PMID- 25619091
TI  - [Job satisfaction and happy caregivers].

PMID- 25619092
TI  - [The concept of well-being in the workplace].
AB  - The concept of wellbeing in the workplace. The concept of wellbeing in the
      workplace has been highlighted in different countries to promote actions relating
      to occupational health. Theories arising from positive psychology help to improve
      understanding of the issues surrounding wellbeing at work, notably in the
      framework of team management.

PMID- 25619093
TI  - [Quality of life at work and quality of work].
AB  - Quality of life at work initiatives centred on the quality of work lead us to
      focus on the company and the contribution of each individual to its performance.
      The consequences of such an approach must be assessed in the light of the work
      published by sociologists and occupational psychologists, together with
      institutional studies on the prevention of psychosocial risks, which have been
      particularly numerous since the 2000s.

PMID- 25619094
TI  - [Work, identity and social ties].
AB  - When a management organisation ruins identity and social cohesion, the work it
      prescribes can be likened to that requested by instinct, which enslaves the
      animal. Wellbeing in the workplace is encouraged by recognition of the actual
      work carried out, a source of self-fulfillment.

PMID- 25619095
TI  - [Work collectives, challenges for employees and management].
AB  - Collectives play an important role in resolving work-related difficulties.
      However, they were significantly destabilised by managerial policies which saw
      them as a hotbed for opposition. Now, management is seeking to recreate the
      collective to improve cooperation and efficiency.

PMID- 25619096
TI  - [Job satisfaction, a collective collaboration].
AB  - Pleasure at work must not be understood as a personal variable or as the
      automatic consequence of a pleasant environment. On the contrary, it is a case of
      constructing, as a group, the conditions for pleasure at work, linked to the
      quality of social relations, the feeling of accomplishment and recognition.

PMID- 25619097
TI  - [A support unit and relaxation area for caregivers].
AB  - A confidential and anonymous support unit, led by a nurse and a psychologist, has
      been created for caregivers within a hospital. It also has a relaxation area
      where they can learn different relaxation techniques. The aim of these places is
      to promote workers' wellbeing and prevent psychosocial risks.

PMID- 25619098
TI  - [Job satisfaction for fulfilled caregivers].
AB  - Pleasure at work for fulfilled caregivers. The notion of pleasure at work is
      linked to the concept of wellbeing. A caregiver who is happy in their activity
      will be a fulfilled professional carrying out their work with compassion and
      rigour. Helping others and making oneself useful by providing care remain sources
      of satisfaction for professionals, as a number of people in the field testify.

PMID- 25619099
TI  - [The coffee break, beneficial for occupational health].
AB  - The coffee break has beneficial effects on health. A form of support for
      healthcare professionals and a way of bringing together the nursing team, it
      boosts the quality of support given to patients and their families, for the
      benefit of the patient's health.

PMID- 25619100
TI  - [Striking the work-life balance].
AB  - Solutions for finding a satisfactory balance between home life and work lie in
      the organisation of work and the work environment. Line managers in particular
      have a key role to play in helping their staff maintain this balance.

PMID- 25619101
TI  - [Quality of care and quality of life at work].
AB  - A criterion concerning quality of life at work was introduced into the V2010
      French National Authority for Health (HAS) certification handbook. The HAS has
      developed programmes to ensure this dimension is included in projects for
      developing healthcare institutions and in the organisation of care.

PMID- 25619102
TI  - [A favorable workplace for nurses].

PMID- 25619103
TI  - [Bibliography. Job satisfaction and well-being at work].

PMID- 25619105
TI  - [E-learning, distance education and continuing professional education].

PMID- 25619104
TI  - [The benefits of systematic reviews for decision-making in clinical practice].
AB  - Information consolidation plays an essential role in providing clinical
      practitioners quick access to reliable information. In this respect, systematic
      reviews help to establish a link between the information arising from research
      and the decision-making regarding patient care. They are significantly beneficial
      for nursing and allied healthcare clinical practices.

PMID- 25619106
TI  - Root nodule bacteria from Clitoria ternatea L. are putative invasive nonrhizobial
      endophytes.
AB  - In this study, bacteria (8 species and 5 genera) belonging to the classes
      Betaproteobacteria, Gammaproteobacteria, and Sphingobacteria were isolated from
      root nodules of the multipurpose legume Clitoria ternatea L. and identified on
      the basis of partial 16S rRNA sequencing. The root nodule bacteria were subjected
      to phenotypic clustering and diversity studies using biochemical kits, including
      Hi-Media CarbokitTM, EnterobacteriaceaeTM identification kit, ERIC-PCR, and 16S
      ARDRA. All the strains showed growth on Ashby's N-free media over 7 generations,
      indicative of presumptive nitrogen fixation and further confirmed by
      amplification of the nifH gene. None of the strains showed the capability to
      renodulate the host plant, neither alone nor in combination with standard
      rhizobial strains, which was further confirmed by the absence of nodC bands in
      PCR assay. The results clearly indicate the common existence of nonrhizobial
      microflora inside the root nodules of legumes, which were thought to be colonized
      only by rhizobia and were responsible for N2 fixation in leguminous crops.
      However, with the recent discovery of nodule endophytes from a variety of
      legumes, as also observed here, it can be assumed that symbiotic rhizobia are not
      all alone and that these invasive endophytes belonging to various bacterial
      genera are more than just opportunistic colonizers of specialized nodule niche. 

PMID- 25619107
TI  - Abstracts of the 8th Annual Congress of the European Association for Haemophilia
      and Allied Disorders, 11-13 February 2015, Helsinki, Finland.

PMID- 25619108
TI  - Decompressing posthaemorrhagic ventricular dilatation significantly improves
      regional cerebral oxygen saturation in preterm infants.
AB  - AIM: This study aimed to delineate the impact of posthaemorrhagic ventricular
      dilatation (PHVD) on regional cerebral oxygen saturation (rcSO2) in preterm
      infants before and after ventricular decompression using near-infrared
      spectroscopy (NIRS). METHODS: rcSO2 values were recorded, fractional tissue
      oxygen extraction (FTOE) was calculated, cerebral ultrasound scans were
      performed, and resistive indices and ventricular width were collected before and
      after decompression. Where possible, amplitude-integrated electroencephalography
      (aEEG) and visual evoked potentials (VEPs) were recorded before and after
      decompression. RESULTS: We included nine preterm infants: nine with cranial
      ultrasound scan data, eight with NIRS data, seven with aEEG data and four with
      VEPs. The resistive index was stable and remained unchanged after decompression
      in all patients. Before decompression, the mean rcSO2 value was 42.6 +/- 12.9%
      and increased to 55 +/- 12.2% after decompression. With increasing ventricular
      width, FTOE showed a mean value of 0.51 +/- 0.05 and decreased to a mean of 0.39
      +/- 0.12 after decompression. Amplitude-integrated electroencephalography showed
      a more continuous pattern, and VEPs showed delayed latencies in all patients
      before intervention, improving afterwards. CONCLUSION: Near-infrared spectroscopy
      may be of additional clinical value in progressive PHVD to determine the optimal
      time point for ventricular decompression.

PMID- 25619109
TI  - Fetal cytomegalovirus infection manifesting as transient pancytopenia.
AB  - We encountered a patient with a fetal cytomegalovirus infection manifesting as
      pancytopenia and thoracic hypoplasia. The fetal anemia was treated by transfusion
      via the umbilical cord, and did not progress after 22 weeks' gestation. The
      neutropenia resolved spontaneously, and only thrombocytopenia was persistent at
      birth. The severe thoracic hypoplasia led to pulmonary hypertension and required
      intensive postnatal respiratory management. Our experience suggests that
      pancytopenia is a possible manifestation in fetuses infected with
      cytomegalovirus. This may be transient, resolving spontaneously during fetal
      life; however, caution should be taken with blood counts, particularly platelet
      counts, after delivery. In addition, clinicians should carefully follow the
      thoracic volume in cytomegalovirus-infected fetuses and consider the possibility
      of postnatal severe respiratory insufficiency. 

PMID- 25619111
TI  - Comparative reevaluation of FASP and enhanced FASP methods by LC-MS/MS.
AB  - Filter-aided sample preparation is a proteomic technique for the preparation and
      on column proteolysis of proteins. Recently an enhanced FASP protocol was
      developed that uses deoxycholic acid (DCA) and that reportedly enhances trypsin
      proteolysis, resulting in increases cytosolic and membrane protein
      representation. FASP and eFASP were re-evaluated by ultra-high-performance liquid
      chromatography coupled to a quadrupole mass filter Orbitrap analyzer (Q
      Exactive). Although there was no difference in trypsin activity, 14,099 and
      13,414 peptides, describing 1723 and 1793 protein groups, from Escherichia coli
      K12 were identified using FASP and eFASP, respectively. Characterization of the
      physicochemical properties of identified peptides showed no significant
      differences other than eFASP extracting slightly more basic peptides. At the
      protein level, both methods extracted essentially the same number of hydrophobic
      transmembrane helix-containing proteins as well as proteins associated with the
      cytoplasm or the cytoplasmic and outer membranes. By employing state-of-the-art
      LC-MS/MS shot gun proteomics, our results indicate that FASP and eFASP showed no
      significant differences at the protein level. However, because of the slight
      differences in selectivity at the physicochemical level of peptides, these
      methods can be seen to be somewhat complementary for analyses of complex peptide
      mixtures.

PMID- 25619110
TI  - Long-term mortality, remission, criminality and psychiatric comorbidity of heroin
      dependence: 11-year findings from the Australian Treatment Outcome Study.
AB  - AIMS: To determine the long-term mortality, remission, criminality and
      psychiatric comorbidity during 11 years among heroin-dependent Australians.
      DESIGN: Longitudinal cohort study. SETTING: Sydney, Australia. PARTICIPANTS: A
      total of 615 participants were recruited and completed baseline interviews
      between 2001 and 2002. Participants completed follow-up interviews at 3, 12, 24
      and 36 months post-baseline, and again at 11 years post-baseline; 431 (70.1%) of
      the original 615 participants completed the 11-year follow-up. MEASUREMENTS:
      Participants were administered the Australian Treatment Outcome Study (ATOS)
      structured interview, addressing demographics, treatment history, drug use,
      heroin overdose, criminality, health and mental health at all interviews.
      Overall, 96.1% of the cohort completed at least one follow-up interview.
      FINDINGS: At 11 years, 63 participants (10.2%) were deceased. The proportion of
      participants who reported using heroin in the preceding month decreased
      significantly from baseline (98.7%) to 36-month follow-up (34.0%; odds ratio =
      0.01; 95% confidence interval = 0.00, 0.01) with further reductions evident
      between 36 months and 11 years (24.8%). However, one in four continued to use
      heroin at 11 years, and close to one-half (46.6%) were in current treatment. The
      reduction in current heroin use was accompanied by reductions in risk-taking,
      crime and injection-related health problems, and improvements in general physical
      and mental health. The relationship with treatment exposure was varied. Major
      depression was associated consistently with poorer outcome. CONCLUSIONS: In an 11
      year follow-up of patients undergoing treatment for heroin dependence, 10.2% had
      died and almost half were still in treatment; the proportion still using heroin
      fell to a quarter, with major depression being a significant predictor of
      continued use.

PMID- 25619112
TI  - Cyclosporine A increases hair follicle growth by suppressing apoptosis-inducing
      factor nuclear translocation: a new mechanism.
AB  - Cyclosporine A (CsA) enhances hair growth through caspase-dependent pathways by
      retarding anagen-to-catagen phase transition in the hair follicle growth cycle.
      Whether apoptosis-inducing factor (AIF), a protein that induces caspase
      independent apoptosis, can regulate the hair follicle cycle in response to CsA is
      currently unclear. Here, we show that the pro-hair growth properties of CsA are
      in part due to blockage of AIF nuclear translocation. We first isolate hair
      follicles from murine dorsal skin. We then used Western blot,
      immunohistochemistry and immunofluorescence to evaluate the expression and
      localization of AIF in hair follicles. We also determined whether modulation of
      AIF was responsible for the effects of CsA at the anagen-to-catagen transition.
      AIF was expressed in hair follicles during the anagen, catagen and telogen
      phases. There was significant nuclear translocation of AIF as hair follicles
      transitioned from anagen to late catagen phase; this was inhibited by CsA, likely
      due to reduced cyclophilin A expression and attenuated AIF release from
      mitochondria. However, we note that AIF translocation was not completely
      eliminated, which likely explains why the transition to catagen phase was
      severely retarded by CsA, rather than being completely inhibited. We speculate
      that blockade of the AIF signalling pathway is a critical event required for CsA
      dependent promotion of hair growth in mice. The study of AIF-related signalling
      pathways may provide insight into hair diseases and suggest potential novel
      therapeutic strategies. 

PMID- 25619113
TI  - Ambiguous Loss Experienced by Transnational Mexican Immigrant Families.
AB  - In this study, an ambiguous loss framework as described by Boss (1999, Ambiguous
      loss: Learning to live with unresolved grief, First Harvard University Press,
      Cambridge, MA) was used to examine and understand the family experiences of
      Mexican immigrant agricultural workers in Minnesota. Transcripts from interviews
      with 17 workers in Minnesota and 17 family members in Mexico were analyzed using
      qualitative methodology to identify experiences of ambiguous loss in the
      participants' narratives. Key dimensions of ambiguous loss identified in the
      transcripts include: psychological family, feelings of chronic/recurring loss,
      finding support, and meaning making. In the category of psychological family,
      participants in both Mexico and the United States mourned the physical absence of
      their family members and experienced ambiguity regarding family responsibilities,
      but worked to maintain their psychological roles within the family. In the
      category of chronic/recurring loss, participants in both countries experienced
      chronic worry from not knowing if family members were safe, ambiguity regarding
      when the immigrant would return, and chronic stressors that compounded these
      feelings of loss. Participants in both countries coped with both real and
      ambiguous losses by accessing family support and by using ambiguous communication
      to minimize worry. Participants in Mexico also accessed work and community-based
      support. Participants in both countries made meaning of the ambiguous loss by
      identifying ways their lives were improved and goals were met as a result of the
      immigration for agricultural work in Minnesota.

PMID- 25619114
TI  - Activation of the mouse odorant receptor 37 subsystem coincides with a reduction
      of novel environment-induced activity within the paraventricular nucleus of the
      hypothalamus.
AB  - Within the main olfactory system of mammals, a unique subsystem exists that is
      comprised of sensory neurons expressing odorant receptors (ORs) of the OR37
      subfamily. These receptors are exclusive for mammals and are highly conserved
      across species. The mouse OR37 receptor subtypes A, B and C were shown to be
      activated by the long-chain aliphatic aldehydes pentadecanal, hexadecanal and
      heptadecanal, respectively. The search for biological sources of these compounds
      showed that bodily secretions from conspecifics activated the OR37A, B and C
      glomerulus. At the same time, the activity of cells in a target region of
      projection neurons from OR37 glomeruli, the paraventricular nucleus of the
      hypothalamus (PVN), was reduced compared with controls (clean test box). A large
      number of the activated cells in the PVN of mice that were placed into a clean
      test box were corticotropin-releasing hormone cells, indicating an induction of
      the stress axis due to the novel environment. The much lower number of activated
      cells of mice in a box enriched with bodily secretions from conspecifics
      indicated a reduced stress response. As bodily secretions from conspecifics
      activated the OR37 system and simultaneously reduced stress-induced activation of
      the PVN, it was tested whether the ligands for OR37 receptors could induce this
      effect. Indeed, a similarly reduced activity in the PVN was found in mice kept in
      a clean test box and exposed to a mixture of the OR37 ligands delivered via an
      air stream. These data indicate that the OR37 system may play a role in mediating
      a phenomenon called social buffering. 

PMID- 25619115
TI  - Adenomas with high-grade dysplasia and early adenocarcinoma are more likely to be
      sessile in the proximal colon.
AB  - AIM: Size and the sessile morphology of an adenoma may explain why colonoscopy is
      less effective in preventing proximal colonic cancer than distal cancers. We
      wanted to determine if advanced polypoid neoplasms (APNs, i.e. adenoma with high
      grade dysplasia or early adenocarcinoma) are more likely to be sessile and/or
      smaller in the proximal colon. METHOD: We searched our institution's pathology
      database from 2004 to 2012 and identified patients with APNs. Polyps were
      categorized by size, morphology and location in the colon. Average polyp size and
      morphology were determined for each location. RESULTS: During the study period,
      564 patients with APNs were identified. Of these, adenocarcinoma was noted in
      21.6% and high-grade dysplasia in 78.4%. The average patient age was 64.4 years
      and 54.9% were men. The proportion of APNs that were <= 5 mm was 1.7%, <= 10 mm
      19.3% and <= 15 mm 39%. APNs in the proximal colon were larger than those in the
      distal colon, but the difference was not statistically significant (27 vs 24 mm;
      P = 0.06). Eighty-three per cent of APNs in the proximal colon were sessile vs
      57% in the distal colon (P = 0.001). APNs in the proximal colon were almost four
      times more likely to be sessile than in the distal colon (OR = 3.7). A similar
      association was noted for polyps <= 20 mm or polyps with high-grade dysplasia.
      CONCLUSION: APNs in the proximal colon were almost four-times more likely to be
      sessile than those in the distal colon. No difference in the size of polyps was
      noted.

PMID- 25619117
TI  - Characterization of the Immunogenicity and Allergenicity of Two Cow's Milk
      Hydrolysates--A Study in Brown Norway Rats.
AB  - Hypoallergenic infant formulas based on hydrolysed milk proteins are used in the
      diet for cow's milk allergic infants. For a preclinical evaluation of the
      immunogenicity and allergenicity of new protein ingredients for such
      hypoallergenic infant formulas as well as for the investigation of which
      characteristics of hydrolysates that contribute to allergenicity, in vivo models
      are valuable tools. In this study, we examine the immunogenicity and
      allergenicity of two hydrolysates in a Brown Norway (BN) rat model, using i.p.
      dosing, which allows for the use of small quantities. Intact BLG, hydrolysed BLG
      and a hydrolysed whey product suitable for use in extensively hydrolysed formulas
      were thoroughly characterized for protein chemical features and administered to
      BN rats by i.p. immunization with or without adjuvant. Sera were analysed for
      specific IgG and IgE for evaluation of sensitizing capacity, immunogenicity and
      antibody-binding capacity. For evaluation of eliciting capacity a skin test was
      performed. The study showed that the hydrolysates had no residual allergenicity,
      lacking the capacity to sensitize and elicit reactions in the BN rats. Dosing
      with or without adjuvant induced a large difference in immunogenicity. Only
      antibodies from rats sensitized to intact BLG with adjuvant were able to bind the
      hydrolysates, and the whey-based hydrolysate only showed immunogenicity when
      dosed with adjuvant. This study showed that hydrolysates can be evaluated by an
      i.p. animal model, but that the choice of in vitro tests used for evaluation of
      antibody responses may greatly influence the result as well as may the use of
      adjuvant. 

PMID- 25619116
TI  - Phosphorylated and unphosphorylated serine 13 of CDC37 stabilize distinct
      interactions between its client and HSP90 binding domains.
AB  - Folding and maturation of most protein kinases require chaperone assistance. In
      higher eukaryotes, CDC37 is the predominant cochaperone that facilitates the
      transfer of kinase clients to HSP90. Kinase recognition is thought to occur
      through the N-terminal domain, which has, thus far, eluded structure
      determination. Client processing also requires the phosphorylation of the N
      terminal tail at Ser13 by protein kinase CK2 (casein kinase 2). How
      phosphorylation alters the molecular properties of CDC37 is not understood. We
      show that the phosphorylation at Ser13 induces a large shift toward a more
      compact structure, based on ANS fluorescence, while modestly increasing secondary
      structure. Moreover, this transition requires interactions of the N-terminal
      domain and the remainder of CDC37. The stabilizing property of the
      phosphorylation event can be recreated in trans by a (phospho-Ser13) peptide
      derived from the N-terminal tail. However, the phosphorylation-induced transition
      is not dependent on the transferred phosphate group but rather the loss of serine
      like properties at position 13. The complete absence of the N-terminal tail
      results in reduced secondary structure and unresponsiveness to subsequent
      addition of peptides. The N-terminal tail may therefore serve as an
      intramolecular chaperone that ensures that CDC37 assumes one of two readily
      interconvertible states in a manner that impacts the interaction of the client
      binding N-domain and the MC-domains, involved in dimerization and HSP90 binding. 

PMID- 25619118
TI  - Covalent cross-linking of cell-wall polysaccharides through esterified
      diferulates as a maize resistance mechanism against corn borers.
AB  - There is strong evidence to suggest that cross-linking of cell-wall polymers
      through ester-linked diferulates has a key role in plant resistance to pests;
      however, direct experimentation to provide conclusive proof is lacking. This
      study presents an evaluation of the damage caused by two corn borer species on
      six maize populations particularly selected for divergent diferulate
      concentrations in pith stem tissues. Maize populations selected for high total
      diferulate concentration had 31% higher diferulates than those selected for low
      diferulates. Stem tunneling by corn borer species was 29% greater in the
      population with the lowest diferulates than in the population with the highest
      diferulates (31.7 versus 22.6 cm), whereas total diferulate concentration was
      negatively correlated with stem tunneling by corn borers. Moreover, orthogonal
      contrasts between groups of populations evaluated showed that larvae fed in
      laboratory bioassays on pith stem tissues from maize populations with higher
      diferulates had 30-40% lower weight than larvae fed on the same tissues from
      maize populations with lower diferulates. This is the first report that shows a
      direct relationship between diferulate deposition in maize cell walls and corn
      borer resistance. Current findings will help to develop adapted maize varieties
      with an acceptable level of resistance against borers and be useful in special
      kinds of agriculture, such as organic farming. 

PMID- 25619119
TI  - Effective qPCR methodology to quantify the expression of virulence genes in
      Aeromonas salmonicida subsp. salmonicida.
AB  - AIMS: This study aimed to select and validate different methodological strategies
      to quantify the expression of the virulence genes ascC and ascV by qPCR in
      Aeromonas salmonicida subsp. salmonicida (Aer. salmonicida). METHODS AND RESULTS:
      Using the geNorm, Normfinder and BestKeeper algorithms, reference genes for the
      qPCR were selected based on their in vitro expression stabilities in three Aer.
      salmonicida strains. Gene amplification efficiency was calculated by Real-time
      PCR Miner and LinReg PCR programmes, which have not been used previously in the
      analysis of bacterial gene expression. The expression of the ascC and ascV
      virulence genes in a virulent Aer. salmonicida strain was evaluated by three
      quantification models, including single (least or most stable) or three most
      stable reference genes, combined with constant or specific gene amplification
      efficiency. The most stable reference genes were gyrB, proC and rpoC, while rpoD
      and fabD were the least stable. Quantification models showed different expression
      patterns. CONCLUSIONS: The optimal strategy to quantify mRNA expression was to
      use a combination of the three algorithms and the quantification model including
      the three most stable reference genes. Real-time PCR Miner or LinReg PCR were
      valuable tools to estimate amplification efficiency. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The methods used in this study gave more reliable expression data
      using qPCR than previously published methods. The quantification and expression
      dynamics of virulence genes will contribute to a better understanding of how Aer.
      salmonicida interacts with its host and the environment, and therefore to the
      prevention of epizootics due to this pathogen.

PMID- 25619120
TI  - The synergistic effects of dissolved oxygen and pH on N2O production in
      biological domestic wastewater treatment under nitrifying conditions.
AB  - Nitrous oxide (N2O) is a potent greenhouse gas, which is produced during
      nitrifying and denitrifying processes. Some factors and mechanisms affecting N2O
      emission have been reported in previous literature, but wastewater biological
      nitrification is accompanied by a dynamic process of dissolved oxygen (DO)
      consumption and pH reduction, it is more meaningful to study the synergistic
      effects between DO and pH on N2O production. In this study, the synergistic
      effects between DO and pH on N2O production were investigated with real domestic
      wastewater. The results showed that high DO levels and a high pH could improve
      the oxidation ratio of NH4+-N and the production ratio of NO2--N, while
      effectively reducing the accumulation ratio of N2O. The NH4+-N was a prerequisite
      for nitrifier denitrification; when NH4+-N was oxidized completely, there would
      be no N2O production and an even higher concentration of NO2- The pH factor is
      shown to directly affect N2O emission, although free ammonia and free nitrous
      acid which changed with pH had no correlation with N2O emission. There were two
      reasons: (1) pH can influence the flow direction of electrons afforded by NH2OH
      oxidation; at high pH, electrons were mainly used for combining H+ and O2
      (O2+4H++4e-=2H2O), the accumulation of NO2- cannot be a result of
      denitrification, and a higher DO can get more electrons to prefer NO2- and (2)
      NH4+ was the prerequisite for NH2OH oxidation, since NH2OH oxidation process was
      the way to provide electrons for nitrifier denitrification.

PMID- 25619121
TI  - Neuropeptide FF inhibits LPS-mediated osteoclast differentiation of RAW264.7
      cells.
AB  - Neuropeptide FF (NPFF) has been implicated in many physiological processes.
      Previously, we have reported that NPFF modulates the viability and nitric oxide
      (NO) production of RAW264.7 macrophages. In this study, we investigated the
      influence of NPFF on lipopolysaccharide (LPS)-mediated osteoclast formation of
      RAW264.7 cells. Our results suggest that, NPFF dose-dependently (1 nM, 10 nM and
      100 nM) inhibited osteoclast formation, TRAP enzyme activity and bone resorption
      in osteoclasts induced by LPS respectively. Moreover, LPS-provoked NO release was
      also inhibited by NPFF treatment, indicating a NO-dependent pathway is mainly
      involved. Furthermore, the alterations of osteoclast marker genes were also
      assessed including TRAP, Cathepsin K, MMP-9, NFATc1 and Runx2. NPFF downregulated
      LPS-caused gene augmentations of TRAP, Cathepsin K and MMP-9, whereas showed no
      influences on NFATc1 and Runx2. In addition, NPFF receptor 2 (NPFFR2) mRNA
      expression was also augmented in response to NPFF treatment, hinting the
      involvement of NPFFR2 pathway. It should be mentioned that RF9 (1 u M), a
      reported pharmacological inhibitor for NPFF receptors, exerted NPFF-like agonist
      properties as to attenuate osteoclastogenesis. Collectively, our findings provide
      new evidence for the in vitro activity of NPFF on osteoclasts, which may be
      helpful to extend the scope of NPFF functions. 

PMID- 25619122
TI  - Analysis of Interactions and Dissection of Interfaces Involved in RNA-Protein
      Recognition.
AB  - RNA-protein recognition is an important component of many cellular processes,
      such as gene expression, protein synthesis, replication of many viruses, etc.
      Primary to the understanding of the functional implications of RNA-protein
      interactions is an in-depth analysis of the molecular mechanisms by which
      proteins identify and discriminate between specific RNA molecules. To gain some
      insight into the structural and physicochemical interactions that happen when a
      protein binds to RNA, an analysis of a non-redundant dataset of 61 RNA-protein
      complexes is presented. Between the two components, 2056 A2 of surface area is
      buried and the larger interfaces tend to be made up of multiple patches. The
      interfaces can be dissected into core and rim regions and distinct preferences of
      residues in the two regions are evident. The residues in the core have smaller
      sequence entropy as compared to the rim, indicating greater sequence
      conservation. Interfaces have been classified based on the composition of the
      secondary structural elements found therein. Various physicochemical parameters
      have been used to compare the protein-RNA interfaces with those found in protein
      protein and protein- DNA complexes. 

PMID- 25619123
TI  - Ancient DNA and human evolution.

PMID- 25619124
TI  - Centchroman vs tamoxifen for regression of mastalgia: a randomized controlled
      trial.
AB  - INTRODUCTION: Several agents have been tried in the management of mastalgia.
      Centchroman (Ormeloxifene), a novel non-steroidal selective estrogen receptor
      modulator (SERM), has also been recently used in the management of mastalgia.
      METHODS: Eligible patients, who had mastalgia for more than 3 months, were
      randomized into two groups - Group A received centchroman 30 mg daily and Group B
      received tamoxifen 10 mg daily. Treatment was continued for a total of 12 weeks;
      thereafter, patients were followed for another 12 weeks without medication to
      assess the continuum of relief. Pain severity was measured with VAS score.
      Patients were considered to have complete pain relief if their VAS score
      decreased to 3 or less. RESULTS: Patients, in both the groups, showed gradual
      improvement in mastalgia with passage of time up to 12 weeks. Following cessation
      of treatment at 12 weeks, partial relapse of pain was observed at 24 weeks. There
      was no significant difference between Group A and Group B in terms of mean VAS
      Score and proportion of women reporting pain relief at 4, 8, 12, and 24 weeks.
      Fifteen patients in Group A had side effects namely dizziness, menstrual
      irregularities and development of ovarian cysts. There was no side effect noted
      in group B. CONCLUSION: Centchroman and tamoxifen were found to be of similar
      effectiveness in providing pain relief in mastalgia. High frequency of side
      effects, particularly development of ovarian cyst, in patients receiving
      centchroman is a matter of concern.

PMID- 25619125
TI  - Inverse relationship of bleeding risk with clot burden during pulmonary embolism
      treatment with LMW heparin.
AB  - INTRODUCTION: Clinically relevant bleeding occurs three times as frequently as
      recurrent venous thromboembolism in the modern early treatment of pulmonary
      embolism (PE) with fixed-dose, unmonitored anticoagulants. Unfractionated heparin
      (UFH) is monitored and adjusted to assure efficacy and minimize bleeding risk,
      but low molecular weight heparin (LMWH) is not. PE requires more anticoagulant
      than isolated deep venous thrombosis. Speculating that PE with low clot burden
      could lead to excess bleeding with unadjusted LMWH treatment but not with UFH, we
      compared PE patients receiving either UFH or LMWH with high and low clot burden
      for clinically significant bleeding in an observational study. MATERIALS AND
      METHODS: Patients with acute PE at multiple Chinese teaching hospitals had been
      randomized to UFH or LMWH for initial treatment. These treatment cohorts had
      baseline measurement of pulmonary artery obstruction (PAO) score, which was
      prospectively separated into quartiles, lowest to highest PAO. All patients were
      followed for bleeding episodes, which were subsequently analyzed by quartile of
      PAO. RESULTS: Two hundred seventy-four patients divided between the two groups
      had similar efficacy and safety outcomes (12 clinically significant bleeds in the
      UFH group vs 15 in the LMWH group). LMWH recipients with the smallest clot
      burdens (lowest PAO quartiles) had highest bleeding rates (Cochran-Armitage trend
      test, P trend = 0.048), but there was no such trend for UFH recipients.
      CONCLUSIONS: For UFH, excess anticoagulant pro-hemorrhagic potential is down
      adjusted via activated partial thromboplastin time monitoring, but for LMWH it is
      not. For PE patients at high bleeding risk, UFH may be safer if the clot burden
      is small.

PMID- 25619126
TI  - Hydrometallurgical recovery of metal values from sulfuric acid leaching liquor of
      spent lithium-ion batteries.
AB  - Environmentally hazardous substances contained in spent Li-ion batteries, such as
      heavy metals and nocuous organics, will pose a threat to the environment and
      human health. On the other hand, the sustainable recycling of spent lithium-ion
      batteries may bring about environmental and economic benefits. In this study, a
      hydrometallurgical process was adopted for the comprehensive recovery of nickel,
      manganese, cobalt and lithium from sulfuric acid leaching liquor from waste
      cathode materials of spent lithium-ion batteries. First, nickel ions were
      selectively precipitated and recovered using dimethylglyoxime reagent. Recycled
      dimethylglyoxime could be re-used as precipitant for nickel and revealed similar
      precipitation performance compared with fresh dimethylglyoxime. Then the
      separation of manganese and cobalt was conducted by solvent extraction method
      using cobalt loaded D2EHPA. And McCabe-Thiele isotherm was employed for the
      prediction of the degree of separation and the number of extraction stages needed
      at specific experimental conditions. Finally, cobalt and lithium were
      sequentially precipitated and recovered as CoC2O4 ? 2H2O and Li2CO3 using
      ammonium oxalate solution and saturated sodium carbonate solution, respectively.
      Recovery efficiencies could be attained as follows: 98.7% for Ni; 97.1% for Mn,
      98.2% for Co and 81.0% for Li under optimized experimental conditions. This
      hydrometallurgical process may promise a candidate for the effective separation
      and recovery of metal values from the sulfuric acid leaching liquor.

PMID- 25619127
TI  - Pollution control up in the air.

PMID- 25619128
TI  - Epichloae infection in a native South African grass, Festuca costata Nees.
AB  - Fungal endophytes have been documented in almost all terrestrial plant groups.
      Although the endophyte infection syndrome in agronomic cultivars is well studied,
      relatively little work addresses questions of spatial ecology and fire effects on
      epichloae endophyte infection in native grasses, and none, to our knowledge, in
      sub-Saharan Africa. We sampled seven populations of the native Festuca costata
      Nees along the spline of the Drakensberg range in South Africa at several spatial
      scales, including both recently burned and unburned stands. We tested epichloae
      presence and prevalence with immunoblot assays, PCR and genetic sequencing. We
      found epichloae endophytes were present and prevalent (38-98% infection rates
      depending on location). Variation in infection rates occurred primarily among
      locations, but also among bunches. There was little evidence that endophyte
      infection rates varied with fire. Novel evidence of epichloae infection of a
      native Festuca in South Africa opens the door to several new research questions,
      from the phylogenetic relationship between epichloae of sub-Saharan Africa and
      other continents to the ecological advantages or disadvantages that endophytes
      confer upon their hosts, especially in a fire-prone ecosystem vulnerable to
      global environmental change. 

PMID- 25619129
TI  - Absence of system xc- in mice decreases anxiety and depressive-like behavior
      without affecting sensorimotor function or spatial vision.
AB  - There is considerable preclinical and clinical evidence indicating that abnormal
      changes in glutamatergic signaling underlie the development of mood disorders.
      Astrocytic glutamate dysfunction, in particular, has been recently linked with
      the pathogenesis and treatment of mood disorders, including anxiety and
      depression. System xc- is a glial cystine/glutamate antiporter that is
      responsible for nonvesicular glutamate release in various regions of the brain.
      Although system xc- is involved in glutamate signal transduction, its possible
      role in mediating anxiety or depressive-like behaviors is currently unknown. In
      the present study, we phenotyped adult and aged system xc- deficient mice in a
      battery of tests for anxiety and depressive-like behavior (open field, light/dark
      test, elevated plus maze, novelty suppressed feeding, forced swim test, tail
      suspension test). Concomitantly, we evaluated the sensorimotor function of system
      xc- deficient mice, using motor and sensorimotor based tests (rotarod, adhesive
      removal test, nest building test). Finally, due to the presence and potential
      functional relevance of system xc- in the eye, we investigated the visual acuity
      of system xc- deficient mice (optomotor test). Our results indicate that loss of
      system xc- does not affect motor or sensorimotor function, in either adult or
      aged mice, in any of the paradigms investigated. Similarly, loss of system xc-
      does not affect basic visual acuity, in either adult or aged mice. On the other
      hand, in the open field and light/dark tests, and forced swim and tail suspension
      tests respectively, we could observe significant anxiolytic and antidepressive
      like effects in system xc- deficient mice that in certain cases (light/dark,
      forced swim) were age-dependent. These findings indicate that, under
      physiological conditions, nonvesicular glutamate release via system xc- mediates
      aspects of higher brain function related to anxiety and depression, but does not
      influence sensorimotor function or spatial vision. As such, modulation of system
      xc- might constitute the basis of innovative interventions in mood disorders. 

PMID- 25619130
TI  - Is the ICH score a valid predictor of mortality in intracerebral hemorrhage?
AB  - PURPOSE: The intracerebral hemorrhage (ICH) score utilizes a 0- to 6-point
      scoring system to predict 30-day mortality in ICH patients. The purpose of this
      analysis was to (a) validate the ICH score in an international, heterogeneous
      population of ICH patients; and (b) assess the usefulness of a 72-h ICH score.
      DATA SOURCES: Analyses were based on data from 399 patients in the Novo Nordisk
      trial F7ICH-1371. The ICH score's ability to predict mortality was determined by
      calculating the sensitivity, specificity, and positive predictive value (PPV).
      CONCLUSIONS: Both the baseline and 72-h ICH score had high specificity but low
      sensitivity resulting in an overall PPV of 57%-76%. Specificity of the ICH score
      was higher in the baseline ICH score (95%) as compared to the 72-h score (89%).
      Sensitivity of the ICH score was higher in the 72-h ICH score (75%) as compared
      to the baseline score (36%). IMPLICATIONS FOR PRACTICE: The baseline ICH score
      provides reasonable PPV while the 72-h score provides higher sensitivity. ICH
      scores obtained at baseline and/or 72 h are valid and may help practitioners to
      more accurately predict 30-day mortality in ICH patients.

PMID- 25619131
TI  - Muscle spindles exhibit core lesions and extensive degeneration of intrafusal
      fibers in the Ryr1(I4895T/wt) mouse model of core myopathy.
AB  - Muscle spindles from the hind limb muscles of adult Ryr1(I4895T/wt) (IT/+) mice
      exhibit severe structural abnormalities. Up to 85% of the spindles are separated
      from skeletal muscle fascicles by a thick layer of connective tissue. Many
      intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and
      collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and
      pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this
      animal model and of core myopathy patients. Spindle abnormalities precede those
      in extrafusal fibers, indicating that they are a primary pathological feature in
      this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed
      for human core myopathy patients, would provide an explanation for an array of
      devastating clinical features characteristic of these diseases and provide novel
      insights into the pathology of RYR1-related myopathies. 

PMID- 25619132
TI  - S-nitrosylation of mouse galectin-2 prevents oxidative inactivation by hydrogen
      peroxide.
AB  - Galectins are a group of animal lectins characterized by their specificity for
      beta-galactosides. Galectin-2 (Gal-2) is predominantly expressed in the
      gastrointestinal tract. A proteomic analysis identified Gal-2 as a protein that
      was S-nitrosylated when mouse gastric mucosal lysates were reacted with S
      nitrosoglutathione, a physiologically relevant S-nitrosylating agent. In the
      present study, recombinant mouse (m)Gal-2 was S-nitrosylated using
      nitrosocysteine (CysNO), which had no effect on the sugar-binding specificity and
      dimerization capacity of the protein. On the other hand, mGal-2 oxidation by H2O2
      resulted in the loss of sugar-binding ability, while S-nitrosylation prevented
      H2O2-inducted inactivation, presumably by protecting the Cys residue(s) in the
      protein. These results suggest that S-nitrosylation by nitric oxides protect Gal
      2 from oxidative stress in the gastrointestinal tract.

PMID- 25619133
TI  - The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells
      in ovarian cancer.
AB  - While an increase in progression free survival time is seen when an angiogenesis
      inhibitor is used in the treatment of high-relapse rate ovarian cancer, it has
      little effect on overall survival. A possible cause of treatment-resistance to
      angiogenesis inhibitors is the growth of stem cells in a hypoxic microenvironment
      built inside the tumor tissue by angiogenesis inhibition. In this study, we
      examined the possible suppression of stem cell and cancer stem cell (CSC)
      expansion by hypoxic cytotoxin, TX-402. TX-402, an analogue of tirapazamine, has
      been developed as a hypoxia selective prodrug with inhibitory effects of HIF-1
      and angiogenesis. We considered TX-402 as a possible molecular-target drug
      candidate for ovarian cancer due to its inhibition of CSC expansion. In this
      study, we found that the expressions of HIF-1alpha and HIF-2alpha were increased
      under hypoxia in serous ovarian cancer cell lines. The expressions of HIF-1alpha
      and HIF-2alpha induced under hypoxia were repressed by TX-402 in a dose-dependent
      manner. Next, we investigated the effects of hypoxia on the expression levels of
      stem cell factors, Oct4, Nanog, Sox2 and Lin28, and showed that their expressions
      were induced by hypoxia. It was also observed that the expressions of putative
      ovarian cancer stem cell markers, CD133 and CD44 were induced under hypoxia.
      Furthermore, TX-402 was found to dose-dependently inhibit the expressions of CSC
      markers and stem cell factors. Oct4 expression was repressed by HIF-2alpha
      silencing, but not by HIF-1alpha silencing, indicating that TX-402 may repress
      the expression of Oct4 by inhibiting HIF-2alpha. We constructed CaOV3 spheroids
      as a 3-dimensional hypoxia model, in which the internal hypoxic region contained
      CSC-like cells expressing Oct4. The internal hypoxic region, which contained Oct4
      expressing cells, disappeared following TX-402 treatment. In conclusion, hypoxia
      promoted the expansion of CSCs expressing CD133 and CD44 accompanied by an
      increase of stem cell factors. Its inhibition of hypoxia-induced CSC expansion
      makes TX-402 promising agent usable in combination for ovarian cancer therapy.

PMID- 25619135
TI  - Structural changes of linear DNA molecules induced by cisplatin.
AB  - Interaction between long DNA molecules and activated cisplatin is believed to be
      crucial to anticancer activity. However, the exact structural changes of long DNA
      molecules induced by cisplatin are still not very clear. In this study,
      structural changes of long linear double-stranded DNA (dsDNA) and short single
      stranded DNA (ssDNA) induced by activated cisplatin have been investigated by
      atomic force microscopy (AFM). The results indicated that long DNA molecules
      gradually formed network structures, beads-on-string structures and their large
      aggregates. Electrostatic and coordination interactions were considered as the
      main driving forces producing these novel structures. An interesting finding in
      this study is the beads-on-string structures. Moreover, it is worth noting that
      the beads-on-string structures were linked into the networks, which can be
      ascribed to the strong DNA-DNA interactions. This study expands our knowledge of
      the interactions between DNA molecules and cisplatin. 

PMID- 25619134
TI  - 17beta-estradiol ameliorates oxygen-induced retinopathy in the early hyperoxic
      phase.
AB  - Retinopathy of prematurity (ROP) is a major and leading cause of blindness in
      premature infants. It has been realized that early treatment for ROP is
      important. However, all the early treatments of ROP are focusing on peripheral
      retinal ablation which does not surmount the limit of extinguishing retinal
      neovascularization and protecting the retinas of children with ROP from the
      injury of ablation. In this study, we investigated the morphological changes of
      retina and oxidative stress alterations in the early phase of oxygen-induced
      retinopathy (OIR) and tested the effects of 17beta-estradiol (17beta-E2), a
      nonselective estrogen receptor (ER) agonist, on early phase OIR development. We
      found that large central capillary-free areas were induced in the retinas of pups
      exposed to hyperoxia on postnatal day 9 (P9), whereas vascularization was almost
      complete in the retinas of pups exposed to normoxia at the same age. The
      concentrations of malondiadehyde (MDA), an end-product of oxidative stress, and
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a major enzyme
      producing free radicals, as well as the activity of NADPH oxidase were
      significantly elevated in the retinas of pups exposed to hyperoxia on P9 and
      postnatal day 13 (P13) compared to those in age matched pups exposed to normoxia.
      Treatment with 17beta-E2 decreased not only the percentage of the central
      capillary-free area to total retina area but also the concentrations of MDA and
      NADPH oxidase as well as the activity of NADPH oxidase in a dose-dependent manner
      in pups exposed to hyperoxia on p9 and P13. The concentration of VEGF was
      significantly decreased on P9 but increased on P14 in the retinas of pups exposed
      to hyperoxia, whereas it was significantly elevated on P9 but decreased on P14 in
      the retinas of pups treated with 17beta-E2. The effect of 17beta-E2 could be
      reversed by the co-treatment with ICI182780, a high affinity estrogen receptor
      antagonist, which suggested that 17beta-E2 might exert its effect on early
      hyperoxic phase of OIR through estrogen receptor. Our results suggest that
      treatment with antioxidant drugs at early hyperoxic phase of ROP even before the
      appearance of retinal neovascularization may be more effective than their
      application to ROP at late phase, which may abolish the deleterious factors that
      contribute to retinal neovascularization and promote retinal blood vessels to
      develop healthily. 

PMID- 25619136
TI  - Type I collagen gel protects murine fibrosarcoma L929 cells from TNFalpha-induced
      cell death.
AB  - Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory
      cytokine TNFalpha. In the present study, we reported on protective effect of type
      I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on
      collagen gel. However, the L929 cells exhibited cobblestone-like morphology which
      was much different from the spread fusiform shape when cultured on conventional
      cell dishes as well as the cells tended to aggregate. On conventional cell
      culture dishes, the cells treated with TNFalpha became round in shape and
      eventually died in a necroptotic manner. The cells cultured on collagen gel,
      however, were completely unaffected. TNFalpha treatment was reported to induce
      autophagy in L929 cells on the plastic dish, and therefore we investigated the
      effect of collagen gel on induction of autophagy. The results indicated that
      autophagy induced by TNFalpha treatment was much reduced when the cells were
      cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell
      from TNFalpha-induced cell death. 

PMID- 25619137
TI  - Depletion of the cereblon gene activates the unfolded protein response and
      protects cells from ER stress-induced cell death.
AB  - Previous studies showed that cereblon (CRBN) binds to various cellular target
      proteins, implying that CRBN regulates a wide range of cell responses. In this
      study, we found that deletion of the Crbn gene desensitized mouse embryonic
      fibroblast cells to various cell death-promoting stimuli, including endoplasmic
      reticulum stress inducers. Mechanistically, deletion of Crbn activates pathways
      involved in the unfolded protein response prior to ER stress induction. Loss of
      Crbn activated PKR-like ER kinase (PERK) with enhanced phosphorylation of
      eIF2alpha. Following ER stress induction, loss of Crbn delayed dephosphorylation
      of eIF2alpha, while reconstitution of Crbn reversed enhanced phosphorylation of
      PERK and eIF2alpha. Lastly, we found that activation of the PERK/eIF2alpha
      pathway following Crbn deletion is caused by activation of AMP-activated protein
      kinase (AMPK). We propose that CRBN plays a role in cellular stress signaling,
      including the unfolded protein response, by controlling the activity of AMPK. 

PMID- 25619139
TI  - Measuring food availability and accessibility among adolescents: Moving beyond
      the neighbourhood boundary.
AB  - Geographic methods have provided insight about food location availability and
      accessibility in understanding neighbourhood variations in health. However,
      quantifying exposure to food locations within a pre-defined range of an
      individual's residence ignores locations outside of the residential neighbourhood
      encountered in daily life. Global positioning system (GPS) data enables
      exploration of multiple contextual influences on health. This study defines place
      in relation to behaviour, employing GPS data to 1) describe adolescent food
      environments within and outside of the residential buffer, 2) quantify actual
      food location visits, and 3) explore associations between availability and
      accessibility of food locations and dietary intake. Adolescents (N = 380; ages 12
      16), wore GPS loggers for up to seven days. Availability and accessibility of
      food locations were defined by counts and distances to food locations within a 15
      min walk (1 km) of home, as well as within 50 m of an adolescent's GPS track. We
      compared the proportion of food locations within the residential buffer to the
      proportion outside but within the GPS buffer. These proportions were compared to
      counts and distances to food locations actually visited. We explored associations
      between food location availability and accessibility with dietary intake
      variables. Food location availability and accessibility was greater and visits
      occurred more commonly outside of the residential buffer than within it. Food
      location availability and accessibility was greater for urban than suburban and
      rural adolescents. There were no associations between home-based measures of
      availability and accessibility and dietary intake and only one for GPS-based
      measures, with greater distance to convenience stores associated with greater
      fruit and vegetable consumption. This study provides important descriptive
      information about adolescent exposure to food locations. Findings confirm that
      traditional home-based approaches overestimate the importance of the
      neighbourhood food environment, but provide only modest evidence of linkages
      between the food environment beyond the residential neighbourhood boundary and
      dietary intake. 

PMID- 25619138
TI  - Human aqueous humor exosomes.
AB  - Aqueous humor (AH) is a dynamic intraocular fluid that supports the vitality of
      tissues that regulate intraocular pressure. We recently discovered that
      extracellular nanovesicles called exosomes are a major constituent of AH.
      Exosomes function in extracellular communication and contain proteins and small
      RNA. Our goal was to characterize the physical properties of AH exosomes and
      their exosomal RNA (esRNA) content. We isolated exosomes from human AH collected
      during cataract surgery from five patients using serial ultracentrifugation. We
      measured the size and concentration of AH exosomes in solution using nanoparticle
      tracking analysis. We found a single population of vesicles having a mean size of
      121 +/- 11 nm in the unprocessed AH. Data show that centrifugation does not
      significantly affect the mean particle size (121 +/- 11 nm versus 124 +/- 21 nm),
      but does impact the final number of exosomes in solution (87% loss from the
      unprocessed AH; n = 5). We extracted esRNA from the pooled human AH samples using
      miRCURY RNA isolation kit from Exiqon. The quality of extracted esRNA was
      evaluated using Agilent Bioanalyzer 2100 and was used to generate a sequencing
      library for small RNA sequencing with Illumina MiSeq sequencer. More than 10
      different miRNAs were identified; abundant species included miR-486-5p, miR-204,
      and miR-184. We found that the majority of extracellular vesicles in the AH were
      in the exosome size range, suggesting that miRNAs housed within exosomes may
      function in communication between AH inflow and outflow tissues. 

PMID- 25619140
TI  - Sex differences and estrogen regulation of miRNAs in lupus, a prototypical
      autoimmune disease.
AB  - Unique dysregulated expression patterns of microRNAs (miRNAs) have been reported
      in many disease conditions including autoimmune diseases such as systemic lupus
      erythematosus (SLE). We have recently reported that miRNAs are differentially
      expressed not only between autoimmune and control mice, but also between male and
      female lupus-prone mice. This important observation is of potential clinical and
      experimental significance since females have higher incidence, earlier expression
      or severity of lupus when compared to their male counterparts. Further, estrogen
      administration to orchiectomized males accelerates the expression of lupus
      related miRNAs and induces unique miRNA signature profile. Understanding the
      basis of altered miRNAs in autoimmune diseases offers a new paradigm to
      understand autoimmune diseases, including sex-differential susceptibility. In
      this review, we summarize miRNA biogenesis and function, and focus on miRNA
      dysregulation in SLE in the context of sexual bias. Furthermore, the effect of
      estrogen on epigenetic miRNA regulation in relation to SLE is highlighted. 

PMID- 25619141
TI  - A dissociation between selective attention and conscious awareness in the
      representation of temporal order information.
AB  - Previous electrophysiological studies have shown that attentional selection
      processes are highly sensitive to the temporal order of task-relevant visual
      events. When two successively presented colour-defined target stimuli are
      separated by a stimulus onset asynchrony (SOA) of only 10 ms, the onset latencies
      of N2pc components to these stimuli (which reflect their attentional selection)
      precisely match their objective temporal separation. We tested whether such small
      onset differences are accessible to conscious awareness by instructing
      participants to report the category (letter or digit) of the first of two target
      colour items that were separated by an SOA of 10, 20, or 30 ms. Performance was
      at chance level for the 10 ms SOA, demonstrating that temporal order information
      which is available to attentional control processes cannot be utilized for
      conscious temporal order judgments. These results provide new evidence that
      selective attention and conscious awareness are functionally separable, and
      support the hypothesis that attention and awareness operate at different stages
      of cognitive processing.

PMID- 25619143
TI  - Tailoring the amphiphilicity and self-assembly of thermosensitive polymers: end
      capped PEG-PNIPAAM block copolymers.
AB  - In this work we report on the synthesis and self-assembly of a thermo-sensitive
      block copolymer system of n-octadecyl-poly(ethylene glycol)-block-poly(N
      isopropylacrylamide), abbreviated as C18-PEGn-b-PNIPAAMm. We present a facile
      synthetic strategy for obtaining highly tunable thermo-responsive block
      copolymers starting from commercial PEG-based surfactants (Brij(r)) or a C18
      precursor and conjugating with PNIPAAM via an Atom Transfer Radical
      Polymerization (ATRP) protocol. The self-assembly and detailed nanostructure were
      thoroughly investigated in aqueous solutions using both small-angle X-ray and
      neutron scattering (SAXS/SANS) combined with turbidity measurements. The results
      show that the system forms rather well defined classical micellar structures at
      room temperature that first undergo a collapse, followed by inter-micellar
      aggregation upon increasing the temperature. For the pure C18-PNIPAAM system,
      however, rather ill-defined micelles were formed, demonstrating the important
      role of PEG in regulating the nanostructure and the stability. It is found that
      the PEG content can be used as a convenient parameter to regulate the
      thermoresponse, i.e., the onset of collapse and aggregation. A detailed
      theoretical modeling analysis of the SAXS/SANS data shows that the system forms
      typical core-shell micellar structures. Interestingly, no evidence of back
      folding, where PEG allows PNIPAAM to form part of the C18 core, can be found upon
      crossing the lower critical solution temperature (LCST). This might be attributed
      to the entropic penalty of folding a polymer chain and/or enthalpic
      incompatibility between the blocks. The results show that by appropriately
      varying the balance between the hydrophobic and hydrophilic content, i.e. the
      amphiphilicity, tunable thermoresponsive micellar structures can be effectively
      designed. By means of SAXS/SANS we are able to follow the response on the
      nanoscale. These results thus give considerable insight into thermo-responsive
      micellar systems and provide guidelines as to how these systems can be tailor
      made and designed. This is expected to be of considerable interest for potential
      applications such as in nanomedicine where an accurate and tunable thermoresponse
      is required. 

PMID- 25619142
TI  - Revealing mechanisms of selective, concentration-dependent potentials of 4
      hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of
      membrane-associated catalase.
AB  - Tumor cells generate extracellular superoxide anions and are protected against
      superoxide anion-mediated intercellular apoptosis-inducing signaling by the
      expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a
      versatile second messenger generated during lipid peroxidation, has been shown to
      induce apoptosis selectively in malignant cells. The findings described in this
      paper reveal the strong, concentration-dependent potential of 4-HNE to
      specifically inactivate extracellular catalase of tumor cells both indirectly and
      directly and to consequently trigger apoptosis in malignant cells through
      superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4
      HNE caused apoptosis selectively in NOX1-expressing tumor cells through
      inactivation of their membrane-associated catalase, thus reactivating subsequent
      intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed
      by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 uM and
      higher directly inactivated membrane-associated catalase of tumor cells, whereas
      at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on
      initial singlet oxygen formation through H2O2 and peroxynitrite interaction.
      Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased
      superoxide anion generation by NOX1 and amplification of singlet oxygen
      generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4
      HNE and singlet oxygen cooperate in complex autoamplificatory loops during this
      process. The finding of these novel anticancer pathways may be useful for
      understanding the role of 4-HNE in the control of malignant cells and for the
      optimization of ROS-dependent therapeutic approaches including antioxidant
      treatments.

PMID- 25619144
TI  - Diet and colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most common diagnosed cancer in
      men and the second in women. Dietary factors and lifestyle may contribute to the
      increasing CRC incidence, making these issues interesting for both the general
      population and the medical oncology community. OBJECTIVE: The aim of this report
      is to present a review of the published epidemiologic research to date reflecting
      the most current scientific evidence related to diet and CRC risk. DESIGN: EMBASE
      and PubMed-NCBI were searched for relevant articles up to November 2014 that
      identified potential interactions between foods or dietary patterns and CRC risk.
      RESULTS: Obesity increases the risk of CRC by 19%. Regular physical activity
      reduces this risk by 24%. CRC risk derived from red meat intake is influenced by
      both total intake and its frequency. Fish consumption may decrease CRC risk by
      12% whereas garlic intake is not significantly associated with reduced CRC risk.
      Intakes of more than 20g/day of fiber are associated with a 25% reduction of CRC
      risk and 525mL/day of milk reduces colon cancer risk by 26% in men. Moderate
      amounts of alcohol (25-30g/day) increase CRC risk. CONCLUSIONS: CRC is a
      preventable disease through the modification of associated risk factors,
      including physical inactivity, obesity and overweight, excessive meat intake,
      smoking and alcoholic beverage consumption. Nonetheless, epidemiological evidence
      in this regard is not conclusive so further research is warranted.

PMID- 25619145
TI  - A salen-type Dy4 single-molecule magnet with an enhanced energy barrier and its
      analogues.
AB  - Four isomorphic tetranuclear lanthanide complexes, namely
      [Ln4(L)2(HL)2(NO3)2(OH)2](NO3)2.4H2O (Ln = Dy (1); Tb (2); Ho (3); Er (4)),
      constructed using hexadentate salen-type ligand N,N'-bis(3-methoxy
      salicylidene)cyclohexane-1,2-diamine, have been isolated. X-ray crystallographic
      analysis reveals that all of the complexes 1-4 are of discrete tetranuclear
      structure with a unique {Ln4O8} core in which four lanthanide ions are coplanar
      in a rhombic frame. There are two crystallographically unequivalent lanthanide
      ions, that is the Ln1(III) ion which is nine-coordinated in a monocapped square
      antiprismatic geometry of the C(4v) point group and the Ln2(III) ion which is
      eight-coordinated in a distorted bicapped trigonal-prismatic geometry of the
      C(2v) point group. Magnetic analysis reveals that complex 1 exhibits two slow
      magnetic relaxations with the highest energy barrier among the reported
      tetranuclear salen-type dysprosium SMMs. This further extends the available SMMs
      of salen-type lanthanide complexes.

PMID- 25619146
TI  - Prognostic significance of YY1 protein expression and mRNA levels by
      bioinformatics analysis in human cancers: a therapeutic target.
AB  - Conventional therapeutic treatments for various cancers include chemotherapy,
      radiotherapy, hormonal therapy and immunotherapy. While such therapies have
      resulted in clinical responses, they were coupled with non-tumor specificity,
      toxicity and resistance in a large subset of the treated patients. During the
      last decade, novel approaches based on scientific knowledge on the biology of
      cancer were exploited and led to the development of novel targeted therapies,
      such as specific chemical inhibitors and immune-based therapies. Although these
      targeted therapies resulted in better responses and less toxicity, there still
      remains the problem of the inherent or acquired resistance. Hence, current
      studies are seeking additional novel therapeutic targets that can overcome
      several mechanisms of resistance. The transcription factor Yin Yang 1 (YY1) is a
      ubiquitous protein expressed in normal and cancer tissues, though the expression
      level is much higher in a large number of cancers; hence, YY1 has been considered
      as a potential novel prognostic biomarker and therapeutic target. YY1 has been
      reported to be involved in the regulation of drug/immune resistance and also in
      the regulation of EMT. Several excellent reviews have been published on YY1 and
      cancer (see below), and, thus, this review will update recently published reports
      as well as report on the analysis of bioinformatics datasets for YY1 in various
      cancers and the relationship between reported protein expression and mRNA levels.
      The potential clinical significance of YY1 is discussed.

PMID- 25619147
TI  - Ab initio calculation of anion proton affinity and ionization potential for
      energetic ionic liquids.
AB  - Developing a better understanding of the bulk properties of ionic liquids
      requires accurate measurements of the underlying molecular properties that help
      to determine the bulk behavior. Two computational methods are used in this work:
      second-order perturbation theory (MP2) and completely renormalized coupled
      cluster theory [CR-CC(2,3)], to calculate the proton affinity and ionization
      potential of a set of anions that are of interest for use in protic, energetic
      ionic liquids. Compared with experimental values, both methods predict similarly
      accurate proton affinities, but CR-CC(2,3) predicts significantly more accurate
      ionization potentials. It is concluded that more time intensive methods like CR
      CC(2,3) are required in calculations involving open shell states like the
      ionization potential.

PMID- 25619148
TI  - What transmission trees reveal about Ebola.

PMID- 25619150
TI  - Can proteomics-based diagnostics aid clinical psychiatry?
AB  - Despite major advances in infrastructure and instrumentation, proteomics-driven
      translational applications have not yet yielded the results that the scientific
      community has envisaged. In this viewpoint, the perspective of proteomics-based
      diagnostics in the field of clinical psychiatry is explored. The challenges that
      proteomics faces in the context of translational approaches are outlined and
      directions toward a successful clinical implementation are provided. Additional
      challenges that psychiatric disorders pose for clinical proteomics are
      highlighted and the potential of proteomics-based, blood tests for psychiatric
      disorders is being assessed. Proteomics offers a valuable toolkit for clinical
      translation that needs to be handled in a pragmatic manner and with realistic
      expectations. 

PMID- 25619149
TI  - Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in
      2014: an observational study.
AB  - BACKGROUND: An epidemic of Ebola virus disease of unprecedented size continues in
      parts of west Africa. For the first time, large urban centres such as Conakry,
      the capital of Guinea, are affected. We did an observational study of patients
      with Ebola virus disease in three regions of Guinea, including Conakry, aiming to
      map the routes of transmission and assess the effect of interventions. METHODS:
      Between Feb 10, 2014, and Aug 25, 2014, we obtained data from the linelist of all
      confirmed and probable cases in Guinea (as of Sept 16, 2014), a laboratory
      database of information about patients, and interviews with patients and their
      families and neighbours. With this information, we mapped chains of transmission,
      identified which setting infections most probably originated from (community,
      hospitals, or funerals), and computed the context-specific and overall
      reproduction numbers. FINDINGS: Of 193 confirmed and probable cases of Ebola
      virus disease reported in Conakry, Boffa, and Telimele, 152 (79%) were positioned
      in chains of transmission. Health-care workers contributed little to
      transmission. In March, 2014, individuals with Ebola virus disease who were not
      health-care workers infected a mean of 2.3 people (95% CI 1.6-3.2): 1.4 (0.9-2.2)
      in the community, 0.4 (0.1-0.9) in hospitals, and 0.5 (0.2-1.0) at funerals.
      After the implementation of infection control in April, the reproduction number
      in hospitals and at funerals reduced to lower than 0.1. In the community, the
      reproduction number dropped by 50% for patients that were admitted to hospital,
      but remained unchanged for those that were not. In March, hospital transmissions
      constituted 35% (seven of 20) of all transmissions and funeral transmissions
      constituted 15% (three); but from April to the end of the study period, they
      constituted only 9% (11 of 128) and 4% (five), respectively. 82% (119 of 145) of
      transmission occurred in the community and 72% (105) between family members. Our
      simulations show that a 10% increase in hospital admissions could have reduced
      the length of chains by 26% (95% CI 4-45). INTERPRETATION: In Conakry,
      interventions had the potential to stop the epidemic, but reintroductions of the
      disease and poor cooperation of a few families led to prolonged low-level spread,
      showing the challenges of Ebola virus disease control in large urban centres.
      Monitoring of chains of transmission is crucial to assess and optimise local
      control strategies for Ebola virus disease. FUNDING: Labex IBEID, Reacting,
      PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar.

PMID- 25619151
TI  - Sugar recognition: designing artificial receptors for applications in biological
      diagnostics and imaging.
AB  - At the cellular level, numerous processes ranging from protein folding to disease
      development are mediated by a sugar-based molecular information system that is
      much less well known than its DNA- or protein-based counterparts. The subtle
      structural diversity of such sugar tags nevertheless offers an excellent, if
      challenging, opportunity to design receptors for the selective recognition of
      biorelevant sugars. Over the past 40 years, growing interest in the field of
      sugar recognition has led to the development of several promising artificial
      receptors, which could soon find widespread use in medical diagnostics and cell
      imaging. 

PMID- 25619152
TI  - The (un)coupling between action execution and observation: comment on "Grasping
      synergies: a motor-control approach to the mirror neuron mechanism" by D'Ausilio,
      Bartoli and Maffongelli.

PMID- 25619153
TI  - New trends in mathematical biology: from the subcellular scale to cell
      populations and tissues: comment on "On the interplay between mathematics and
      biology. Hallmarks toward a new systems biology" by N. Bellomo et al.

PMID- 25619154
TI  - Primary Sjogren's syndrome at a glance today.

PMID- 25619155
TI  - Flare in spondyloarthritis: Thresholds of disease activity variations.
AB  - There is no definition of flare in spondyloarthritis (SpA). The aim of this study
      was to evaluate thresholds of disease activity variations using validated
      composite indexes. METHODS: SpA patients (ASAS criteria) prospectively followed
      with at least two visits, were evaluated. Patients and physician answered at each
      visit the question: "do you consider your SpA/patient in a state of flare?".
      Variations of BASDAI and ASDAS between visits were assessed and associated to the
      change of perception of a flare (yes/no). ROC curves were built to assess
      thresholds of variation in BASDAI and ASDAS associated with the change flare
      between visits. RESULTS: The patients were issued from a prospective series of
      250 SpA. Ninety-nine cases with at least 2 visits were analysed. They were: 67%
      men, mean age 45+/-12 years; disease duration: 16+/-10 years; 84% HLA-B27
      positive; purely axial SpA: 81%; PASS at baseline: 56%; mean CRP: 8.6+/-13.5mg/l.
      Mean BASDAI and ASDAS-CRP at baseline were 4.3+/-2.2 and 2.5+/-1.1, respectively.
      The kappa coefficient of agreement between patient and physician for considering
      a flare was 0.68. The main results of the ROC curves are: a variation >=2.1 units
      in BASDAI (sensitivity 59%, specificity 83%), 0.8 units in ASDAS-ESR (sen 56%,
      spe 91%) or 1.3 units in ASDAS-CRP (sen 47%, spe 100%) is associated to a flare.
      CONCLUSION: We propose thresholds of variations of BASDAI, ASDAS-ESR, and ASDAS
      CRP associated to (and that may define) a flare, as considered by the patient and
      the physician.

PMID- 25619156
TI  - Obesity reduces the drug survival of second line biological drugs following a
      first TNF-alpha inhibitor in rheumatoid arthritis patients.
AB  - OBJECTIVES: The aim of this study was to assess whether body mass index (BMI)
      affects clinical outcomes in rheumatoid arthritis (RA) patients starting a second
      line biological drug after failure of a first TNF-alpha blocker. METHODS: From a
      longitudinal cohort, we analyzed 292 RA patients (66 obese, 109 overweight, and
      117 normal-weight) treated with a first ever anti-TNF-alpha drug. Patients
      discontinuing the therapy were followed-up if began a second biological drug.
      Drug survival, by Kaplan-Meier life analysis, and 12 months disease remission
      based on the 28-joint Disease Activity Score (DAS28) were assessed for either
      course of biologics. The baseline predictors of clinical outcomes were assessed
      by Cox regression analysis. RESULTS: Survival of the first anti-TNF-alpha drug
      was lower in obese (39.4%) than in normal-weight (49.1%) patients, but the
      difference was not statistically significant. Obese patients had the highest
      hazard to discontinue the first anti-TNF-alpha drug (HR 1.64, 1.02-2.62 95% IC,
      P=0.04), and the lowest percentage of DAS28-based disease remission at 12 months
      (P=0.04). In 97 (37 normal-weight, 36 overweight, 24 obese) patients who started
      a second non-anti-TNF-alpha biological drug, persistence on therapy was
      significantly lower in obese (43.5%) than in normal-weight (80%, P=0.04) group,
      and again obesity significantly predicted drug discontinuation (HR 2.9, 1.08-8.45
      95% IC, P=0.04). Significantly, less obese patients attained a disease remission
      (12%, P=0.004) at 12 months. CONCLUSION: Our study provides evidence that obese
      RA patients poorly respond to second line non-anti-TNF-alpha drugs after failure
      of a first TNF-alpha inhibitor.

PMID- 25619157
TI  - Assessment of the educational impact of an information leaflet on the knowledge
      of complications in systemic sclerosis.

PMID- 25619158
TI  - Influence of conversion material morphology on electrochemistry studied with
      operando X-ray tomography and diffraction.
AB  - X-ray diffraction and X-ray tomography are performed on intermetallic particles
      undergoing lithiation in a porous electrode. Differences between ensemble phase
      evolution and that at a single-particle level are explored. It is found that all
      particles evidence core-shell lithiation; however, particles with internal
      porosity are more mechanically robust and exhibit less fracture. 

PMID- 25619159
TI  - Polyoxometalates-based heterometallic organic-inorganic hybrid materials for
      rapid adsorption and selective separation of methylene blue from aqueous
      solutions.
AB  - A series of LnCu-polyoxometalates (POMs) were used for dye-wastewater treatment
      with rapid (within 1 min) and large-scale adsorption (up to 391.3 mg g(-1)) as
      well as excellent selective separation of cationic dyes. Furthermore, the
      adsorbed dyes can be easily desorbed, and the POMs still work very efficiently
      even after three cycles. 

PMID- 25619160
TI  - PPARgamma upregulation induced by vagus nerve stimulation exerts anti
      inflammatory effect in cerebral ischemia/reperfusion rats.
AB  - BACKGROUND: It is well known that peroxisome proliferator-activated receptor
      gamma (PPARgamma), a ligand-activated transcription factor, plays a protective
      role in anti-inflammatory responses in both acute and chronic central nerve
      system (CNS) insults. Emerging evidence in rats suggests that vagus nerve
      stimulation (VNS), while restraining inflammatory cytokine production in the
      peripheral nervous system, also exerts a significant CNS neuroprotective function
      against ischemic stroke injury. The aim of this study was to explore the role of
      PPARgamma in VNS-mediated anti-inflammatory protection against ischemic stroke
      damage. MATERIAL/METHODS: Adult male Sprague-Dawley rats (total n=160)
      preconditioned through transfection with either PPARgamma small interfering RNA
      (siRNA) or lentiviral vector without siRNA and surgically subjected to middle
      cerebral artery occlusion and reperfusion subsequently received VNS treatment at
      30 min post-occlusion. The expression of PPARgamma after VNS treatment was
      measured by real-time PCR and Western blotting, also supported by
      immunofluorescence staining. Subsequently, the neurological deficits scores, the
      infarct volume, and the brain histopathology were all evaluated. Additionally,
      the influence on the pro-inflammatory cytokines expression and neuro-immune cells
      activation was determined by ELISA and immunofluorescence staining. RESULTS: We
      found that VNS upregulated expression of PPARgamma in ischemia penumbra,
      diminished the extent of ischemic infarct, alleviated neuronal injury, and
      suppressed pro-inflammatory cytokine expression and immune cell activation
      (P<0.05). However, rats with PPARgamma silencing failed to manifest significant
      neuroprotection and anti-inflammatory effect induced by VNS treatment (p>0.05).
      CONCLUSIONS: PPARgamma may participate in the process by which VNS modulates the
      neuro-inflammatory response following ischemia/reperfusion in rats.

PMID- 25619161
TI  - Lithium and sexual dysfunction: an under-researched area.
AB  - OBJECTIVE: Lithium treatment remains an important part of the management of many
      patients with bipolar disorder, but the incidence of treatment-emergent sexual
      dysfunction with lithium is uncertain, and little is known about how it might be
      managed. METHOD: Systematic computerised literature search of preclinical and
      clinical studies. RESULTS: Thirteen relevant papers were identified. Preclinical
      studies suggest lithium can reduce testosterone levels and impair nitric oxide
      mediated relaxation of cavernosal tissue. Clinical reports suggest lithium may
      reduce sexual thoughts and desire, worsen erectile function and reduce sexual
      satisfaction. Concomitant benzodiazepine prescription with lithium is associated
      with an increased risk of sexual dysfunction. Sexual dysfunction during lithium
      treatment appears significantly associated with a lower level of overall
      functioning and may reduce compliance. CONCLUSION: The findings of this
      systematic review reveal the paucity of information about the incidence,
      associated factors and management of sexual dysfunction with lithium treatment
      and highlight the need for well-designed studies in this area.

PMID- 25619162
TI  - On the pH dependence of class-1 RF-dependent termination of mRNA translation.
AB  - We have studied the pH dependence of the rate of termination of bacterial protein
      synthesis catalyzed by a class-1 release factor (RF1 or RF2). We used a classical
      quench-flow technique and a newly developed stopped-flow technique that relies on
      the use of fluorescently labeled peptides. We found the termination rate to
      increase with increasing pH and, eventually, to saturate at about 70 s(-1) with
      an apparent pKa value of about 7.6. From our data, we suggest that class-1 RF
      termination is rate limited by the chemistry of ester bond hydrolysis at low pH
      and by a stop-codon-dependent and pH-independent conformational change of RFs at
      high pH. We propose that RF-dependent termination depends on the participation of
      a hydroxide ion rather than a water molecule in the hydrolysis of the ester bond
      between the P-site tRNA and its peptide chain. We provide a simple explanation
      for why the rate of termination saturated at high pH in our experiments but not
      in those of others.

PMID- 25619163
TI  - Palliative care and decision making in advanced heart failure.
AB  - OPINION STATEMENT: The diagnosis of advanced heart failure (HF) is established in
      patients for whom symptoms are refractory to guideline-directed therapies.
      Palliative care (PC) is based on symptom management and support of the patient
      and family, making its integration into the care of those with advanced HF
      essential. Comorbidities including frailty, cognitive dysfunction, and depression
      are often under-recognized in patients with advanced HF and may correlate with
      outcomes. Decisions should be based on the patient's values, goals agreed upon by
      the clinician with the patient, and what is medically reasonable. Palliative Care
      should be integrated to help with both palliation of symptoms and support for
      families and patients.

PMID- 25619166
TI  - Swelling-induced surface instability patterns guided by pre-introduced
      structures.
AB  - Swelling-induced, spontaneously generated surface instability patterns in
      substrate-attached hydrogel films can be harnessed for advanced applications,
      however, methods to control their formation and morphology are missing. Here we
      propose that their generation may be guided by intentionally pre-introduced line
      structures. While uniform gel films produce irregular polygonal instability
      patterns, instability patterns generated in pre-patterned films with hexagonal
      line structures are regular hexagons with long-range order. The pre-introduced
      line structures act as defects in the generation of the surface instability
      patterns, which determine the position of the creases, regulate their
      rearrangement and determine their final morphology. The contrast between the pre
      introduced structures and the surrounding area should be high enough for the pre
      introduced structures to act as defects. Only when the characteristic wavelength
      of the pre-introduced pattern matches with the one of the gel film, perfect
      hexagonal patterns can be obtained. The gel films with uniform topographic
      features may find various advanced applications. 

PMID- 25619165
TI  - [Shock-induced anterior ischemic optic neuropathy from hemorrhagic anemia].
AB  - A 51-year-old diabetic and overweight male presented to our eye clinic with right
      sided impairment of visual acuity and scotoma. A thorough work-up had been
      carried out at our institute 9 months prior to this event due to left-sided
      nonarteriitic anterior ischemic optic neuropathy (NAION). Despite the similarity
      of visual symptoms in the currently and previously affected eyes microcystic
      anemia (Hb 81 g/dl) associated with severe hemorrhoidal bleeding was diagnosed.
      The patient underwent surgical hemorrhoidectomy and received two red blood cell
      concentrates. Therefore, this article reports on an extraordinarily rare case of
      shock-induced anterior ischemic optic neuropathy (SIAION) caused by hemorrhoidal
      bleeding. 

PMID- 25619167
TI  - High-performance supercapacitors using graphene/polyaniline composites deposited
      on kitchen sponge.
AB  - We in this study used a commercial grade kitchen sponge as the scaffold where
      both graphene platelets (GnPs) and polyaniline (PANi) nanorods were deposited.
      The high electrical conductivity of GnPs (1460 S cm(-1)) enhances the pseudo
      capacitive performance of PANi grown vertically on the GnPs basal planes; the
      interconnected pores of the sponge provide sufficient inner surface between the
      GnPs/PANi composite and the electrolyte, which thus facilitates ion diffusion
      during charge and discharge processes. When the composite electrode was used to
      build a supercapacitor with two-electrode configuration, it exhibited a specific
      capacitance of 965.3 F g(-1) at a scan rate of 10 mV s(-1) in 1.0 M H2SO4
      solution. In addition, the composite Nyquist plot showed no semicircle at high
      frequency corresponding to a low equivalent series resistance of 0.35 Omega. At
      100 mV s(-1), the supercapacitor demonstrated an energy density of 34.5 Wh kg(-1)
      and a power density of 12.4 kW kg(-1) based on the total mass of the active
      materials on both electrodes. To demonstrate the performance, we built an array
      consisting of three cells connected in series, which lit up a red light emitting
      diode for five minutes. This simple method holds promise for high-performance yet
      low-cost electrodes for supercapacitors. 

PMID- 25619164
TI  - CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future
      considerations.
AB  - Melanoma remains a critical public health problem worldwide. Patients with stage
      IV disease have very poor prognosis and their 1-year survival rate is only 25%.
      Until recently, systemic treatments with a positive impact on overall survival
      (OS) had remained elusive. In recent years, the United States Food and Drug
      Administration (FDA) - approved several novel agents targeting the
      RAS/RAF/MEK/ERK pathway (vemurafenib, dabrafenib, and trametinib) - critical in
      cell division and proliferation of melanoma, and an immune checkpoint inhibitor
      (ipilimumab) directed against the cytotoxic T lymphocyte Antigen - (CTLA-4).
      Moreover, recent reports of clinical trials studying other immune checkpoint
      modulating agents will most likely result in their FDA approval within the next
      months. This review focuses on ipilimumab, its safety and efficacy, and future
      considerations. Ipilimumab has demonstrated a positive OS impact after a several
      year follow-up. It is also recognized that due to its mechanism of action, the
      response patterns to ipilimumab can differ from those observed in patients
      following treatment with conventional cytotoxic agents and even the most recently
      approved BRAF inhibitors. Most patients (84.8%) experience drug-related adverse
      events (AEs) of any grade; most of these are mild to moderate and immune
      mediated. However, a minority of patients may also experience severe and life
      threatening AEs. In clinical studies, AEs were managed according to guidelines
      that emphasized close clinical monitoring and early use of corticosteroids when
      appropriate. Preliminary results have taught us the potential greater toxicity
      when in combination with vemurafenib, and the greater antitumor efficacy when
      combined with nivolumab, a monoclonal antibody directed against programmed death
      receptor-1 (PD-1), another immune checkpoint inhibitor. Future challenges include
      the optimization of dosing and toxicities when used as a single agent, and
      studying the safety and efficacy of combinations with targeted small molecules
      and other monoclonal antibodies to treat patients with melanoma and other
      malignancies. 

PMID- 25619168
TI  - Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the
      Framingham Heart Study.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes mellitus in parents is a strong determinant of
      diabetes risk in their offspring. We hypothesise that offspring diabetes risk
      associated with parental diabetes is mediated by metabolic risk factors. METHODS:
      We studied initially non-diabetic participants of the Framingham Offspring Study.
      Metabolic risk was estimated using beta cell corrected insulin response (CIR),
      HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score
      [MSS]). Dietary risk and physical activity were estimated using questionnaire
      responses. Genetic risk score (GRS) was estimated as the count of 62 type 2
      diabetes risk alleles. The outcome of incident diabetes in offspring was examined
      across levels of parental diabetes exposure, accounting for sibling correlation
      and adjusting for age, sex and putative mediators. The proportion mediated was
      estimated by comparing regression coefficients for parental diabetes with (beta
      adj) and without (beta unadj) adjustments for CIR, HOMA-IR, MSS and GRS
      (percentage mediated = 1 - beta adj / beta unadj). RESULTS: Metabolic factors
      mediated 11% of offspring diabetes risk associated with parental diabetes,
      corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS
      mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from
      2.13 to 1.99. CONCLUSIONS/INTERPRETATION: Metabolic risk factors partially
      mediated offspring type 2 diabetes risk conferred by parental diabetes to a
      similar magnitude as genetic risk. However, a substantial proportion of offspring
      diabetes risk associated with parental diabetes remains unexplained by metabolic
      factors, genetic risk, diet and physical activity, suggesting that important
      familial influences on diabetes risk remain undiscovered.

PMID- 25619169
TI  - An intestinal Trojan horse for gene delivery.
AB  - The intestinal epithelium forms an essential element of the mucosal barrier and
      plays a critical role in the pathophysiological response to different enteric
      disorders and diseases. As a major enteric dysfunction of the intestinal tract,
      inflammatory bowel disease is a genetic disease which results from the
      inappropriate and exaggerated mucosal immune response to the normal constituents
      in the mucosal microbiota environment. An intestine targeted drug delivery system
      has unique advantages in the treatment of inflammatory bowel disease. As a new
      concept in drug delivery, the Trojan horse system with the synergy of
      nanotechnology and host cells can achieve better therapeutic efficacy in specific
      diseases. Here, we demonstrated the feasibility of encapsulating DNA
      functionalized gold nanoparticles into primary isolated intestinal stem cells to
      form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel
      disease. This proof-of-concept intestinal Trojan horse will have a wide variety
      of applications in the diagnosis and therapy of enteric disorders and diseases. 

PMID- 25619170
TI  - Low-dose hydrocortisone reduces norepinephrine duration in severe burn patients:
      a randomized clinical trial.
AB  - INTRODUCTION: The aim of this study was to assess the effect of low-dose
      corticosteroid therapy in reducing shock duration after severe burn. METHODS: A
      placebo-controlled, double-blind, randomized clinical trial (RCT) was performed
      on two parallel groups in the burn intensive care unit (ICU). Patients were
      randomized to receive either low-dose corticosteroid therapy or placebo for seven
      days. A corticotropin test was performed at the time of randomization, before the
      administration of the treatment dose. Thirty-two severely burned patients with
      refractory shock (>0.5 MUg/kg/min of norepinephrine) were prospectively included
      in the study. RESULTS: We included 12 patients in the hydrocortisone-treated
      group and 15 patients in the placebo group in the final analysis. Among these
      patients, 21 were nonresponders to the corticotropin test. Median norepinephrine
      treatment duration (primary objective) was significantly lower in the
      corticosteroid-treated versus the placebo group (57 hours versus 120 hours, P =
      0.035). The number of patients without norepinephrine 72 hours after inclusion
      was significantly lower in the treated group (P = 0.003, log-rank test analysis).
      The total quantities of norepinephrine administered to patients were lower in the
      hydrocortisone-treated versus the placebo group (1,205 MUg/kg (1,079 to 2,167)
      versus 1,971 MUg/kg (1,535 to 3,893), P = 0.067). There was no difference in
      terms of ICU or hospital length of stay, sepsis incidence, cicatrization or
      mortality. CONCLUSIONS: In this placebo-controlled, randomized, double-blind
      clinical trial, we show for the first time that the administration of low-dose
      hydrocortisone in burn patients with severe shock reduces vasopressor
      administration. TRIAL REGISTRATION: Clinicaltrial.gov NCT00149123 . Registered 6
      September 2005.

PMID- 25619171
TI  - Evaluation of strategies to control Fab light chain dimer during mammalian
      expression and purification: A universal one-step process for purification of
      correctly assembled Fab.
AB  - Fabs are an important class of antibody fragment as both research reagents and
      therapeutic agents. There are a plethora of methods described for their
      recombinant expression and purification. However, these do not address the issue
      of excessive light chain production that forms light chain dimers nor do they
      describe a universal purification strategy. Light chain dimer impurities and the
      absence of a universal Fab purification strategy present persistent challenges
      for biotechnology applications using Fabs, particularly around the need for
      bespoke purification strategies. This study describes methods to address light
      chain dimer formation during Fab expression and identifies a novel CH 1 affinity
      resin as a simple and efficient one-step purification for correctly assembled
      Fab.

PMID- 25619172
TI  - Structure of mycobacterial maltokinase, the missing link in the essential GlgE
      pathway.
AB  - A novel four-step pathway identified recently in mycobacteria channels trehalose
      to glycogen synthesis and is also likely involved in the biosynthesis of two
      other crucial polymers: intracellular methylglucose lipopolysaccharides and
      exposed capsular glucan. The structures of three of the intervening enzymes -
      GlgB, GlgE, and TreS - were recently reported, providing the first templates for
      rational drug design. Here we describe the structural characterization of the
      fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a
      eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and
      aminoglycoside phosphotransferases. The 1.15 A structure of Mak in complex with a
      non-hydrolysable ATP analog reveals subtle structural rearrangements upon
      nucleotide binding in the cleft between the N- and the C-terminal lobes.
      Remarkably, this new family of ELKs has a novel N-terminal domain topologically
      resembling the cystatin family of protease inhibitors. By interfacing with and
      restraining the mobility of the phosphate-binding region of the N-terminal lobe,
      Mak's unusual N-terminal domain might regulate its phosphotransfer activity and
      represents the most likely anchoring point for TreS, the upstream enzyme in the
      pathway. By completing the gallery of atomic-detail models of an essential
      pathway, this structure opens new avenues for the rational design of alternative
      anti-tubercular compounds. 

PMID- 25619173
TI  - A case study using the PrOACT-URL and BRAT frameworks for structured benefit risk
      assessment.
AB  - While benefit-risk assessment is a key component of the drug development and
      maintenance process, it is often described in a narrative. In contrast,
      structured benefit-risk assessment builds on established ideas from decision
      analysis and comprises a qualitative framework and quantitative methodology. We
      compare two such frameworks, applying multi-criteria decision-analysis (MCDA)
      within the PrOACT-URL framework and weighted net clinical benefit (wNCB), within
      the BRAT framework. These are applied to a case study of natalizumab for the
      treatment of relapsing remitting multiple sclerosis. We focus on the practical
      considerations of applying these methods and give recommendations for visual
      presentation of results. In the case study, we found structured benefit-risk
      analysis to be a useful tool for structuring, quantifying, and communicating the
      relative benefit and safety profiles of drugs in a transparent, rational and
      consistent way. The two frameworks were similar. MCDA is a generic and flexible
      methodology that can be used to perform a structured benefit-risk in any common
      context. wNCB is a special case of MCDA and is shown to be equivalent to an
      extension of the number needed to treat (NNT) principle. It is simpler to apply
      and understand than MCDA and can be applied when all outcomes are measured on a
      binary scale. 

PMID- 25619174
TI  - Diabetic cystopathy: A review.
AB  - Herein we review and discuss epidemiological, clinical, and experimental studies
      on diabetic cystopathy, a common chronic complication of diabetes mellitus with a
      variety of lower urinary tract symptoms, providing directions for future
      research. A search of published epidemiological, clinical, or preclinical trial
      literature was performed using the key words "diabetes", "diabetic cystopathy",
      "diabetic bladder dysfunction", "diabetic lower urinary tract dysfunction",
      "diabetic detrusor instability". The classic symptoms of diabetic cystopathy are
      decreased bladder sensation, increased bladder capacity, and impaired bladder
      emptying with resultant increased post-void residual volume. However, recent
      clinical evidence indicates a presence of storage symptoms, such as overactive
      bladder symptoms. The pathophysiology of diabetic cystopathy is multifactorial,
      including disturbances of the detrusor, neuron, urothelium, and urethra.
      Hyperglycemia, oxidative stress, and polyuria play important roles in inducing
      voiding dysfunction in diabetic individuals. Treatment choice depends on clinical
      symptoms and urodynamic abnormalities. Urodynamic evaluation is the cornerstone
      of diagnosis and determines management strategies. Diabetes mellitus could cause
      a variety of lower urinary tract symptoms, leading to diabetic cystopathy with
      broadly varied estimates of the prevalence rates. The exact prevalence and
      pathogenesis of diabetic cystopathy remains to be further investigated and
      studied in multicenter, large-scaled, or randomized basic and clinical trials,
      and a validated and standardized workup needs to be made, improving diabetic
      cystopathy management in clinical practice. Further studies involving only female
      diabetics are recommended. 

PMID- 25619175
TI  - Correlation between Membrane Partitioning and Functional Activity in a Single
      Lipid Vesicle Assay Establishes Design Guidelines for Antiviral Peptides.
AB  - The nanometer-scale discrimination of virus-rupturing peptides is tested using
      lipid membrane platforms. In combination with single-vesicle analysis of peptide
      induced vesicle rupture, a correlation between membrane partitioning and
      biologically relevant activities is established. Taken together, the findings
      support that the degree of rupture activity should be balanced by membrane
      curvature-selectivity for optimal therapeutic properties of antiviral peptides. 

PMID- 25619176
TI  - Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: a
      systematic review and meta-analysis of randomized-controlled trials.
AB  - Limited options are available for clozapine-resistant schizophrenia and
      intolerable side effects of clozapine. We conducted a systematic review of
      randomized-controlled trials (RCTs) to determine the efficacy and safety of
      aripiprazole augmentation of clozapine for schizophrenia. Electronic databases
      searched included PubMed, Scopus, Cochrane Central Register of Controlled Trials,
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of
      Science. This review synthesized the data of four short-term (8-24 weeks),
      placebo-controlled trials (N = 347). The overall relative risk (RR, 95%
      confidence interval) of discontinuation rates was not significantly different
      between groups (RR = 1.41, 95% CI = 0.78 to 2.56). The pooled standardized mean
      differences (SMDs, 95% CIs) (Z-test; number of study; I(2)-index) suggested
      trends of aripiprazole augmentation benefits on overall psychotic [-0.40 (-0.87
      to 0.07) (n = 3; Z = 1.68, p = 0.09; I(2) = 68%)], positive [-1.05 (-2.39 to
      0.29) (n = 3; Z = 1.54, p = 0.12; I(2) = 94%)], and negative [-0.36 (-0.77 to
      0.05) (n = 3; Z = 1.74, p = 0.08; I(2) = 54%)] symptoms. Despite of no benefit on
      three cardiometabolic indices (i.e., fasting plasma glucose, triglyceride, and
      high-density lipoprotein), aripiprazole augmentation was superior for weight
      change with a mean difference (95% CI) of -1.36 kg (-2.35 to -0.36) (n = 3; Z =
      2.67, p = 0.008; I(2) = 39%) and LDL-cholesterol with a mean difference of -11.06
      mg/dL (-18.25 to -3.87) (n = 3; Z = 3.02, p = 0.003; I(2) = 31%). Aripiprazole
      augmentation was not correlated with headache and insomnia but significantly
      associated with agitation/akathesia (RR = 7.59, 95% CI = 1.43 to 40.18) (n = 3; Z
      = 2.38, p = 0.02; I(2) = 0%) and anxiety (RR = 2.70, 95% CI = 1.02 to 7.15) (n =
      1; Z = 2.00, p = 0.05). The limited short-term data suggested that aripiprazole
      augmentation of clozapine can minimize the cardiometabolic risk, causes
      agitation/akathesia, and may be effective in attenuating psychotic symptoms.

PMID- 25619177
TI  - [Work hard to develop neuro-ophthalmology in China].
AB  - Neuro-ophthalmology is a crossing discipline. Optic neuritis and ischemic optic
      neuropathy are the hot points of this field. Currently, studies of optic neuritis
      epidemiology, etiology and clinical features have already been done in china. And
      the expert consensus of optic neuritis therapy was published. The pathogenesis
      and treatment of ischemic optic neuropathy is another hot point. We have embarked
      on the epidemiological study of ischemic optic neuropathy in china. We also
      appeal the ophthalmologists to pay more attention on the therapy of posterior
      visual pathway. 

PMID- 25619178
TI  - [Establishment of diagnosis and treatment patterns of holistic integrated
      medicine for neuro-ophthalmology].
AB  - Neuro-ophthalmology, as an interdisciplinary, covers at least three disciplines-
      ophthalmology, neurology and neurosurgery. With limited knowledge in each
      discipline, doctors often make misdiagnoses for neuro-ophthalmology diseases.
      Therefore, it is imperative to abandon the distinction between disciplines and
      combine all the knowledge to diagnose and treat patients in patterns of holistic
      integrated medicine in order to effectively improve the diagnosis and treatment
      of neuro-ophthalmology. 

PMID- 25619179
TI  - [Clinical feature of chronic compressive optic neuropathy without optic atrophy].
AB  - OBJECTIVE: To investigate the clinical feature of the chronic compressive optic
      neuropathy without optic atrophy. METHODS: Retrospective cases series study. The
      clinical data of 25 patients (37 eyes) with chronic compressive optic neuropathy
      without optic atrophy, treated in Beijing Tongren Eye Center, Beijing Tongren
      Hospital, Capital Medical University, from October, 2005 to March, 2014, were
      collected. Those patients had been showing visual symptoms for 6 months or
      longer, but missed diagnosed or misdiagnosed as other eye diseases due to their
      normal or slightly changed fundi. The collected data including visual acuities,
      visual fields, neuroimaging and/or pathologic diagnosis were analyzed. RESULTS:
      Among the 25 patients, there were 5 males and 20 females, and their ages range
      from 9 to 74 years [average (47.5 +/- 13.4) years]. All patients suffered
      progressive impaired vision in single eye or both eyes, without exophthalmos or
      abnormal eye movements. Except one patient had a headache, other patients did not
      show systemic symptoms. The corrected visual acuities were between HM to 1.0, and
      their appearances of optic discs and colors of fundi were normal. After
      neuroimaging and/or pathological examination, it was proven that 14 patients
      suffered tuberculum sellae meningiomas, 5 patients with hypophysoma, 3 patient
      with optic nerve sheath meningioma in orbital apex, 1 patient with cavernous
      hemangioma, 1 patient with vascular malformation in orbital apex and 1 patient
      with optic nerve glioma. Among the 19 patients whose suffered occupied lesions of
      saddle area, 14 patients underwent visual field examinations, and only 4 patients
      showed classic visual field defects caused by optic chiasmal lesions. CONCLUSION:
      Occult progressive visual loss was the most important clinical feature of the
      disease.

PMID- 25619180
TI  - [Evaluating the risk of ischemic cerebral vascular disease with ocular
      hemodynamics in carotid artery stenosis patients].
AB  - OBJECTIVE: To evaluate the association between the ocular hemodynamic and the
      incidence of ischemic cerebral vascular diseases in carotid artery stenosis
      patients. METHODS: Case-control study. Seventy-two cases patients with carotid
      artery stenosis including 22 cases of cerebral infarction group, 14 cases of
      lacunar cerebral infarction group and the control group of the other 36 patients
      without cerebral infarction were recruited. All patients were measured with
      hemodynamic parameters of the ophthalmic artery, central retinal artery and
      posterior ciliary artery. PSV, EDV, PI and RI were also measured. The other risk
      ischemic cerebral vascular factors were obtained through the questionnaire and
      venous blood sampling. The differences of 3 groups and the influences of the
      other risk factor of hemodynamic were calculated. RESULTS: PSV of ophthalmic
      artery was (25.96 +/- 12.63)cm/s in cerebral infarction group, (32.63 +/- 13.25)
      cm/s in lacunar infarction group and (39.46 +/- 14.97) cm/s in control group. EDV
      of ophthalmic artery was(6.09 +/- 3.10) cm/s in cerebral infarction group, (6.57
      +/- 2.85) cm/s in lacunar infarction group and (9.73 +/- 5.02) cm/s in control
      group. PSV of central retinal artery was (8.06 +/- 2.98) cm/s in cerebral
      infarction group, (8.91 +/- 2.76) cm/s in lacunar infarction group and (9.71 +/-
      2.60) cm/s in control group. The differences were statistically significant (F =
      13.393, 12.609, 5.027, P < 0.01). EDV of central retinal artery was (2.46 +/-
      0.77) cm/s in cerebral infarction group, (2.35 +/- 0.89) cm/s in lacunar
      infarction group and (2.73 +/- 0.86) cm/s in control group. There was no
      statistical difference of EDV of CRA in three group (F = 2.405, P = 0.094).
      CONCLUSIONS: There was association between the ocular hemodynamic parameters and
      the incidence of ischemic cerebrovascular disease in the carotid artery stenosis
      patients. Increased level of PSV and EDV of the ophthalmic artery raised the risk
      of the incidence of ischemic cerebrovascular disease.

PMID- 25619181
TI  - [Clinical investigation of optic coherence tomography in evaluating the
      impairment of optic nerve secondary to multiple sclerosis].
AB  - OBJECTIVE: To evaluate the impairment of optic nerve of different types of
      multiple sclerosis (MS) by optic coherence tomography (OCT). METHODS: Cross
      sectional study. 52 eyes of 30 patients who diagnosed as MS up to the 2010
      Mcdonald criteria were included. 13 eyes of 13 healthy people matched with sex
      and age were set as the control group. Patients with MS were divided into 3
      subgroups based on the history of optic neuritis (ON): 22 eyes of MS patients
      with the history of ON were in MS-ON group, 16 eyes of MS patients without ON
      were in MS-NON group and 14 contralateral eyes of MS-ON patients were in MS-ON
      Contra group. Fourier domain OCT was used to examine. The protocol included
      macula scanning, retinal nerve fiber layer (RNFL) analysis and ganglion cell
      complex (GCC) and optic nerve head (ONH) scanning. Visual acuity (VA) and visual
      field (VF) were also compared. The major measurements were RNFL and GCC
      thickness. ANOVA was used to compare the overall difference of RNFL and GCC
      thickness among all the groups. LSD method was used to compare the difference
      between every two groups. RESULTS: The thickness of average GCC, superior GCC and
      inferior GCC of MS-ON group is (80.65 +/- 16.03) um, (81.50 +/- 14.56) um, (79.83
      +/- 17.65) um. Compared with the MS-NON group which is (99.65 +/- 9.35) um,
      (99.26 +/- 9.73) um, (100.06 +/- 9.31) um correspondingly, MS-ON contra group
      (99.36 +/- 8.25) um, (100.39 +/- 8.97) um, (98.34 +/- 7.88) um correspondingly
      and the control group (104.87 +/- 8.71) um, (105.36 +/- 8.21) um, (103.96 +/-
      10.33) um correspondingly, they decreased significantly (P < 0.05). While the GCC
      thickness has no significantly difference among the MS-NON, MS-ON Contra and the
      control group. The average RNFL thickness and nasal inferior quadrant RNFL
      thickness in MS-ON group was (83.68 +/- 29.91) um, (92.26 +/- 35.97) um. And they
      were significantly thinner than that in the MS-NON group which was (108.83 +/-
      15.33) um, (120.85 +/- 35.96) um correspondingly and that in the control group
      which was (111.60 +/- 14.90) um, (139.95 +/- 7.77) um correspondingly (P < 0.05).
      The RNFL thickness in temporal inferior quadrant in MS-ON group was (109.63 +/-
      44.54) um and it was (60.47 +/- 26.94) um in the temporal quadrant. And they
      decreased significantly compared with that in the MS-NON which was (149.92 +/-
      18.51) um, (90.64 +/- 16.15) um correspondingly, and in the MS-ON Contra group
      which was (135.70 +/- 28.66) um, (77.30 +/- 23.40) um correspondingly and in the
      control group which was (172.72 +/- 15.29) um,( 90.90 +/- 6.15) um
      correspondingly (P < 0.05). The RNFL thickness in nasal inferior, temporal
      inferior and temporal quadrant in the MS-ON Contra group was (106.60 +/- 44.07)
      um, (135.70 +/- 28.66) um, (77.30 +/- 23.40) um respectively which was
      significantly thinner than that in the control group which was (139.95 +/- 7.77)
      um, (172.72 +/- 15.29) um, (90.90 +/- 6.15) um correspondingly (P < 0.05).
      CONCLUSIONS: GCC and RNFL thickness of OCT test can be used to evaluate the
      impairment of optic nerve of MS patients, and the RNFL scanning can reflect the
      early and latent lesion of optic nerve in MS.

PMID- 25619182
TI  - [Citation analysis of the ocular ischemic syndrome literature].
AB  - OBJECTIVE: To characterize the literature associated with the ocular ischemic
      syndrome (OIS) field from January 1, 2000 to December 1, 2013. METHODS:
      Literature analysis. Articles related to OIS between January 1, 2000 and December
      1, 2013 were found by advanced search using Google Scholar. All results underwent
      visual inspection to ensure that the final results included only literature
      associated with OIS in some way. All the results including the publication year,
      authors, organizations, nations and the source journals were listed and analyzed.
      RESULTS: There were 322 literatures which cited 2 798 times totally. The h-index
      of literature associated with OIS was 28. There were only 6 articles published in
      2000, while 54 articles in 2013 which was significant different. The largest
      number of author is from US, then China and Japan. The most frequent cited
      article was a review which summarized retinal vascular occlusive disorders
      written by Sohan Singh Hayreh. And the other top 10 articles talked about
      intravitreal injection, hemodynamics and its pathogenesis. The hightest h-index
      of author, orgnization, country, and source title was Sohan Singh Hayreh,
      University of Iowa and Utrecht University, United States, and Investigative
      Ophthalmology and Visual Science respectively. CONCLUSIONS: The quantity of the
      articles about OIS growed every year. OIS research is getting more attention
      gradually, particularly in intravitreal injection, hemodynamics and its
      pathogenesis.

PMID- 25619183
TI  - [Radiographic observation of nasolacrimal canal in congenital nasolacrimal canal
      agenesis].
AB  - OBJECTIVE: To explore the radiographic characteristics of nasolacrimal canals in
      congenital nasolacrimal canal agenesis. METHODS: Retrospective case series study.
      The images of Computed Tomography of 18 children with unilateral congenital
      nasolacrimal canal agenesis who were treated in Beijing Children's Hospital from
      January 2009 to June 2013 were studied. The common features of abnormal lacrimal
      canals were analyzed. The heights of bilateral lacrimal canals, anterioposterior
      and transverse diameters at the original level of lacrimal canal were measured.
      The traverse diameters, anteroposterior diameters, heights of bony nasolacrimal
      duct between affected side and normal side were compared using paired t tests.
      RESULTS: The initial segment of abnormal nasolacrimal canal showed no obvious
      abnormalities, but it became significant stenosis or even atresia at the middle
      and terminal segments. The transverse (4.72 +/- 0.79) mm and anterioposterior
      diameters (5.45 +/- 1.07) mm of affected sides were larger than the values of
      normal sides (3.42 +/- 0.67) mm, (4.35 +/- 1.01) mm at the original level of
      nasolacrimal canal with statistically significance (t = 5.665, P = 0.000; t =
      6.610, P = 0.000). However, the height of nasolacrimal canal of normal sides were
      larger than the affected sides (t = 5.931, P = 0.000). CONCLUSIONS: Atresia
      position of congenital nasolacrimal canal agenesis always located in the terminal
      segment. High pressure in the nasolacrimal duct caused by bony obstruction leaded
      to the enlargement of nasolacrimal canal in affected side.

PMID- 25619184
TI  - [Top ten progression of neuro-ophthalmology research in China in the latest five
      years].
AB  - Ten researches that represent the most advanced neuro-ophthalmology related
      studies in china were voted by specialists from Chinese Neuro-ophthalmology
      Society. These researches were concentrated in the following fields: clinical and
      basic researches of optic neuritis, studies of ischemic optic neuropathy, and
      clinical present of Leber's hereditary optic neuropathy. These researches
      represented the level of neuro-ophthalmology in China and also showed the focus
      of our Chinese neuro-ophthalmologists in recent years. 

PMID- 25619185
TI  - [Current status and progress in diagnosis and treatments of pediatric optic
      neuritis].
AB  - Pediatric optic neuritis (ON) is different from its adult counterpart in terms of
      epidemiology, etiology, clinical manifestations, and prognosis. Although adult
      optic neuritis was well described in treatments by the Optic Neuritis Treatment
      Trial (ONTT), there is no universal agreement on the treatments in a pediatric
      population. Since there is an inadequate knowledge about pediatric ON in our
      nation, we compared the clinical manifestations of pediatric ON with its adult
      population, reviewed the existing understanding of the relationship between
      pediatric ON and various diseases of CNS, and summarized the current treatments,
      expecting to provide useful reference in clinic. 

PMID- 25619186
TI  - [Progression of drug delivery system for glaucoma].
AB  - Reduction of intraocular pressure (IOP) by drugs is a major treatment for
      glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP
      through different mechanisms.However, due to limitations of traditional form of
      eye drops, the bioavailability of the drug and the patient compliance is lowered,
      the clinical efficacy is not good and also some toxic and side-effects come
      out.Otherwise, traditional medication is not suitable for neuroprotective drugs
      to work on both retina and optic nerve. Drug delivery system has the potential to
      improve the bioavailability of the drug, prolong the time of drug action,
      decrease the dosage and frequency of drugs, reduce the side-effects, and improve
      the patient compliance and efficacy.It is one of the most important studies in
      glaucoma medication development because it is valuable for patients'
      neuroprotection.Nowadays, several novel delivery systems have been designed. This
      review will focus on the progressions of some of the sustained-release
      antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled
      drug delivery system, ocular implants, and transscleral drug delivery systems. 

PMID- 25619187
TI  - [Research progress of vascular endothelial tip cells in diabetic retinopathy].
AB  - Tip cells are one kind of vascular endothelial cells. Migration and sprouting of
      tip cells is the first step of angiogenesis. In recent years, researchers found a
      large number of tip endothelial cells in new blood vessels of diabetic
      retinopathy patients and animal models. Vascular endothelial growth factor (VEGF)
      regulates the migration and budding of tip cells and dissolves the extracellular
      matrix. Pericyte recruitment guided by the VEGF-DLL-Notch signal pathway is
      necessary for neovascularization. The change of miRNA in tip cells is also
      involved in the regulation of angiogenesis. This paper focuses on the mechanism
      of endothelial tip cells in diabetic retinopathy and prospects for the future
      research of anti-angiogenesis drug targets. 

PMID- 25619189
TI  - Near infrared autofluorescence findings in diffuse subretinal fibrosis syndrome.

PMID- 25619188
TI  - The ectomycorrhizas of Lactarius cuspidoaurantiacus and Lactarius herrerae
      associated with Alnus acuminata in Central Mexico.
AB  - Two pure Alnus acuminata stands established in a montane forest in central Mexico
      (Puebla State) were monitored between 2010 and 2013 to confirm and recognize the
      ectomycorrhizal (EcM) systems of A. acuminata with Lactarius cuspidoaurantiacus
      and Lactarius herrerae, two recently described species. Through comparison of
      internal transcribed spacer (ITS) of nuclear ribosomal DNA sequences from
      basidiomes and ectomycorrhizas sampled in the forest stands, we confirmed their
      ectomycorrhizal association. The phytobiont was corroborated by comparing ITS
      sequences obtained from EcM root tips and leaves collected in the study site and
      from other sequences of A. acuminata available in Genbank. Detailed morphological
      and anatomical descriptions of the ectomycorrhizal systems are presented and
      complemented with photographs. 

PMID- 25619191
TI  - Racial disparities in prostate cancer incidence rates by census division in the
      United States, 1999-2008.
AB  - BACKGROUND: Black men have a higher incidence of prostate cancer than white men
      in the U.S., but little is known whether incidence or racial differences vary
      geographically. Understanding these differences may assist future studies on
      causes of prostate cancer. To address such, we leverage the unique resource of
      the National Program of Cancer Registries (NPCR) combined with Surveillance,
      Epidemiology and End Results (SEER). METHODS: Prostate cancer counts and
      population denominators by race (black, white), age, calendar year, and U.S.
      census division, for the period 1999-2008, were extracted from NPCR and SEER. We
      calculated age-standardized incidence rates (ASR) and estimated annual percent
      changes (EAPC) by race and census division. We assessed black-to-white incidence
      rate ratios (BWIRR) by census division and by calendar period. RESULTS: This
      analysis included 1,713,471 prostate cancer cases and 1,217 million person-years.
      Black ASRs ranged from 176 per 100,000 person-years in Mountain division to 259
      in Middle Atlantic. BWIRRs ranged from 1.20 in Western divisions to 1.72 in
      Southeastern divisions. EAPCs indicated that prostate cancer incidence is not
      decreasing in East South Central, unlike all other divisions. White EAPCs
      displayed similar variations by census division, resulting in modest temporal
      changes in BWIRRs. CONCLUSIONS: Within the U.S., there exists significant
      geographic variability in prostate cancer incidence rates. Although there are
      large geographic differences in BWIRRs, temporal trends are fairly stable. This
      may indicate that primary factors affecting prostate cancer incidence rates vary
      geographically but affect both black and white men to a similar degree.

PMID- 25619192
TI  - Directional learning and the provisioning of public goods.
AB  - We consider an environment where players are involved in a public goods game and
      must decide repeatedly whether to make an individual contribution or not.
      However, players lack strategically relevant information about the game and about
      the other players in the population. The resulting behavior of players is
      completely uncoupled from such information, and the individual strategy
      adjustment dynamics are driven only by reinforcement feedbacks from each player's
      own past. We show that the resulting "directional learning" is sufficient to
      explain cooperative deviations away from the Nash equilibrium. We introduce the
      concept of k-strong equilibria, which nest both the Nash equilibrium and the
      Aumann-strong equilibrium as two special cases, and we show that, together with
      the parameters of the learning model, the maximal k-strength of equilibrium
      determines the stationary distribution. The provisioning of public goods can be
      secured even under adverse conditions, as long as players are sufficiently
      responsive to the changes in their own payoffs and adjust their actions
      accordingly. Substantial levels of public cooperation can thus be explained
      without arguments involving selflessness or social preferences, solely on the
      basis of uncoordinated directional (mis)learning. 

PMID- 25619193
TI  - ABC triblock copolymer micelles: spherical versus worm-like micelles depending on
      the preparation method.
AB  - Well-defined ABC triblock copolymers based on two hydrophilic blocks, A and C,
      and a hydrophobic block B are synthesized and their self-assembly behavior is
      investigated. Interestingly, at the same solvent, concentration, pH, and
      temperature, different shape micelles are observed, spherical and worm-like
      micelles, depending on the preparation method. Specifically, spherical micelles
      are observed with bulk rehydration while both spherical and worm-like micelles
      are observed with film rehydration. 

PMID- 25619194
TI  - Recruiting Chinese- and Korean-Americans in Cancer Survivorship Research:
      Challenges and Lessons Learned.
AB  - This paper describes Asian-American recruitment experiences using data from the
      cancer survivorship study involving Chinese- and Korean-American breast cancer
      survivors specifically. The article discusses challenges to the successful
      recruitment of Asian-American populations for cancer survivorship research and
      provides recommendations for future recruitment efforts. The study investigated
      the role of family communication in coping and quality of life for survivors from
      Chinese- and Korean-American groups diagnosed with breast cancer. Participants
      were primarily recruited through cancer registries and community outreach. A
      total of 157 breast cancer survivors (86 Chinese-Americans and 71 Korean
      Americans) completed the final survey, yielding a final response rate of 62.8 %
      of the accessible samples. Chinese-Americans were more likely to agree to
      participate but less frequently completed the survey, and Korean-Americans were
      more likely to refuse to participate. Common reasons for refusal were "too busy
      or too painful to recall," followed by "not interested," "too old," "distrust of
      the research," or "health issue." Participants were more likely to be young and
      Korean-American compared to non-participants. Cultural and linguistic barriers,
      distrust, and lack of awareness about cancer research should be considered to
      recruit more Asian-American cancer survivors. Community participatory research is
      required to ensure participation by sufficient numbers of ethnic minorities in
      cancer survivorship research.

PMID- 25619195
TI  - Health Information Seeking and Cancer Screening Adherence Rates.
AB  - Effective screening tools are available for many of the top cancer killers in the
      USA. Searching for health information has previously been found to be associated
      with adhering to cancer screening guidelines, but Internet information seeking
      has not been examined separately. The current study examines the relationship
      between health and cancer Internet information seeking and adherence to cancer
      screening guidelines for breast, cervical, and colorectal cancer in a large
      nationally representative dataset. The current study was conducted using data
      from the Health Information National Trends Survey from 2003 and 2007. The study
      examined age-stratified models which correlated health and cancer information
      seeking with getting breast, cervical, and colorectal cancer screening on
      schedule, while controlling for several key variables. Internet health and cancer
      information seeking was positively associated with getting Pap screening on
      schedule, while information seeking from any sources was positively associated
      with getting colorectal screening on schedule. People who look for health or
      cancer information are more likely to get screened on schedule. Some groups of
      people, however, do not exhibit this relationship and, thus, may be more
      vulnerable to under-screening. These groups may benefit more from targeted
      interventions that attempt to engage people in their health care more actively. 

PMID- 25619196
TI  - Patient Beliefs About Colon Cancer Screening.
AB  - Only about half of eligible individuals undergo colon cancer screening. We have
      limited knowledge about the patient beliefs that adversely affect screening
      decisions and about which beliefs might be amenable to change through education.
      As part of a clinical trial, 641 rural Iowans, aged 52 to 79 years, reported
      their beliefs about colon cancer screening in response to a mailed questionnaire.
      Consenting subjects were randomized into four groups, which were distinguished by
      four levels of increasingly intensive efforts to promote screening. Two of the
      groups received mailed educational materials and completed a follow-up
      questionnaire, which allowed us to determine whether their beliefs about
      screening changed following the education. We also completed a factor analysis to
      identify underlying (latent) factors that might explain the responses to 33
      questions about readiness, attitudes, and perceived barriers related to colon
      cancer screening. The strongest predictors of a patient's stated readiness to be
      screened were a physician's recommendation to be screened (1 point difference on
      10-point Likert scale, 95 % confidence interval [CI], 0.5 to 1.6 point
      difference), a family history of colon cancer (0.85-point Likert scale
      difference, 95 % CI, 0.1 to 1.6), and a belief that health-care decisions should
      be mostly left to physicians rather than patients (Spearman correlation
      coefficient 0.21, P < .001). Of the 33 questionnaire items about screening
      beliefs, 11 (33 %) changed favorably following the educational intervention. In
      the factor analysis, the 33 items were reduced to 8 underlying factors, such as
      being too busy to undergo screening and worries about screening procedures. We
      found a limited number of underlying factors that may help explain patient
      resistance to colon cancer screening.

PMID- 25619197
TI  - Circulating microRNAs in heart failure with reduced and preserved left
      ventricular ejection fraction.
AB  - AIM: The potential diagnostic utility of circulating microRNAs in heart failure
      (HF) or in distinguishing HF with reduced vs. preserved left ventricular ejection
      fraction (HFREF and HFPEF, respectively) is unclear. We sought to identify
      microRNAs suitable for diagnosis of HF and for distinguishing both HFREF and
      HFPEF from non-HF controls and HFREF from HFPEF. METHODS AND RESULTS: MicroRNA
      profiling performed on whole blood and corresponding plasma samples of 28
      controls, 39 HFREF and 19 HFPEF identified 344 microRNAs to be dysregulated among
      the three groups. Further analysis using an independent cohort of 30 controls, 30
      HFREF and 30 HFPEF, presented 12 microRNAs with diagnostic potential for one or
      both HF phenotypes. Of these, miR-1233, -183-3p, -190a, -193b-3p, -193b-5p, -211
      5p, -494, and -671-5p distinguished HF from controls. Altered levels of miR-125a
      5p, -183-3p, -193b-3p, -211-5p, -494, -638, and -671-5p were found in HFREF while
      levels of miR-1233, -183-3p, -190a, -193b-3p, -193b-5p, and -545-5p distinguished
      HFPEF from controls. Four microRNAs (miR-125a-5p, -190a, -550a-5p, and -638)
      distinguished HFREF from HFPEF. Selective microRNA panels showed stronger
      discriminative power than N-terminal pro-brain natriuretic peptide (NT-proBNP).
      In addition, individual or multiple microRNAs used in combination with NT-proBNP
      increased NT-proBNP's discriminative performance, achieving perfect intergroup
      distinction. Pathway analysis revealed that the altered microRNAs expression was
      associated with several mechanisms of potential significance in HF. CONCLUSIONS:
      We report specific microRNAs as potential biomarkers in distinguishing HF from
      non-HF controls and in differentiating between HFREF and HFPEF.

PMID- 25619199
TI  - Characterization of solid lipid nanoparticles containing caffeic acid and
      determination of its effects on MCF-7 cells.
AB  - Many anticancer drugs that are currently used in cancer treatment are natural
      products or their analogues by structural modification. Caffeic acid (3, 4
      dihydroxycinnamic acid; CA) is classified as hydroxycinnamic acid and has a
      variety of potential pharmacological effects, including antioxidant,
      immunomodulatory and anti-inflammatory activities. As a drug carrier, solid lipid
      nanoparticles (SLNs) introduced to improve stability, provide controlled drug
      release, avoid organic solvents and are obtained in small sizes. In this study,
      we developed solid lipid nanoparticles incorporating with caffeic acid using hot
      homogenization method. Caffeic acid loaded solid lipid nanoparticles were
      characterized regarding particle size, zeta potential, drug entrapment
      efficiency, drug release, scanning electron microscopy (SEM) and FT-IR. The
      effects of caffeic acid loaded solid lipid nanoparticles on MCF-7 cells were
      determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide
      (MTT) test and Annexin V-PI analysis. As a result, solid lipid nanoparticles
      could potentially be used for the delivery of caffeic acid and solid lipid
      nanoparticles formulation enhanced the effects of caffeic acid on MCF-7 cells.
      Some relevant patents are also referred in this article. 

PMID- 25619198
TI  - Pioneers in pediatric psychology: integrating nutrition and child development
      interventions.
AB  - As part of the Pioneers in Pediatric Psychology series, this article provides a
      brief personal account of Maureen Black's career as a pediatric psychologist. It
      traces the transition of the Society of Pediatric Psychology (SPP) from a section
      of the Division of Clinical Psychology of the American Psychological Association
      (APA) to an independent division of APA, which occurred during my presidency of
      SPP. The article addresses three aspects of pediatric psychology that have been
      central to my career: pediatric nutritional problems, global child development,
      and the advancement of children's health and development through policy-related
      strategies. The article concludes with Lessons Learned and Recommendations for
      the future of pediatric psychology. 

PMID- 25619200
TI  - The current health of the signing Deaf community in the UK compared with the
      general population: a cross-sectional study.
AB  - OBJECTIVES: To assess the current health of the Deaf community in the UK and
      compare with the general population. DESIGN: A quota sample of adult Deaf British
      Sign Language (BSL) users underwent a health assessment and interview in 2012
      2013. Comparative data were obtained from the Health Survey for England (HSE)
      2011 and the Quality Outcomes Framework (QOF) 2012. SETTING: Participants
      completed a structured interview and health assessment at seven Bupa centres
      across the UK, supported in BSL by Deaf advisers and interpreters. PARTICIPANTS:
      298 Deaf people, 20-82 years old, 47% male, with 12% from ethnic minorities. MAIN
      OUTCOME MEASURES: Self-reported health conditions, medication usage, tobacco and
      alcohol consumption; measured blood pressure (BP), body mass index, fasting blood
      sugar and lipid profile. RESULTS: Rates of obesity in the Deaf sample were high,
      especially in those over 65 years, and 48% were in a high risk group for serious
      illness. High BP readings were obtained in 37% of Deaf people (21% in HSE): 29%
      were unaware of this (6% in HSE). Only 42% of Deaf people being treated for
      hypertension had adequate control, compared with 62% of the general population.
      Deaf people with self-reported cardiovascular disease (CVD) were significantly
      less than the general population. One-third of Deaf participants had total
      cholesterol >5 mmol/L but although control rates were high compared with HSE,
      treatment rates for self-reported CVD were half the general population rate.
      Eleven per cent of Deaf participants had blood sugar at prediabetic or diabetic
      levels, and 77% of those at prediabetic levels were unaware of it. Deaf
      respondents self-reported more depression (31% of women, 14% of men), but less
      smoking (8%) and alcohol intake (2-8 units/week). CONCLUSIONS: Deaf people's
      health is poorer than that of the general population, with probable
      underdiagnosis and undertreatment of chronic conditions putting them at risk of
      preventable ill health.

PMID- 25619202
TI  - Performance characteristics of seven bilevel mechanical ventilators in pressure
      support mode with different cycling criteria: a comparative bench study.
AB  - BACKGROUND: Pressure support ventilation from a bilevel device is a standard
      technique for non-invasive home ventilation. A bench study was designed to
      compare the performance and patient-ventilator synchronization of 7 bilevel
      ventilators, in the presence of system leaks. MATERIAL/METHODS: Ventilators were
      connected to a Hans Rudolph Series 1101 lung simulator (compliance, 50 mL/cmH2O;
      expiratory resistance, 20 cmH2O/L/s; respiratory rate, 15 breaths/min;
      inspiratory time, 1.0 s). All ventilators were set at 15 cmH2O pressure support
      and 5 cmH2O positive end-expiratory pressure. Tests were conducted at 2 system
      leaks (12-15 and 25-28 L/min). The performance characteristics and patient
      ventilator asynchrony were assessed, including flow, airway pressure, time, and
      workload. RESULTS: The Breas Vivo30 could not synchronize with the simulator
      (frequent auto-triggering) at a leak of 25-28 L/min, but provided stable assisted
      ventilation when the leak was 12-15 L/min. Missed efforts and back-up ventilation
      occurred for the Weinmann VENTImotion and Airox Smartair Plus, requiring
      adjustment of trigger effort. All ventilators had a short trigger delay time
      (<200 ms), but significant differences between devices were found in triggering
      workload, pressurization appearance, tidal volume, and peak inspiratory flow.
      Premature cycling was frequent when the inspiratory termination criteria were at
      the highest sensitivity. Cycling synchronization was considerably improved by
      modifying expiratory triggering sensitivity settings, when available.
      CONCLUSIONS: Performance and triggering workload varied significantly between
      bilevel ventilators, possibly due to software algorithm differences. Adjusting
      the cycling criteria settings can alter the shape of the inspiratory phase and
      peak expiratory flow, and improve patient-ventilator synchrony.

PMID- 25619201
TI  - Statistical methods for modeling repeated measures of maternal environmental
      exposure biomarkers during pregnancy in association with preterm birth.
AB  - BACKGROUND: It is of critical importance to evaluate the role of environmental
      chemical exposures in premature birth. While a number of studies investigate this
      relationship, most utilize single exposure measurements during pregnancy in
      association with the outcome. The studies with repeated measures of exposure
      during pregnancy employ primarily cross-sectional analyses that may not be fully
      leveraging the power and additional information that the data provide. METHODS:
      We examine 9 statistical methods that may be utilized to estimate the
      relationship between a longitudinal exposure and a binary, non-time-varying
      outcome. To exemplify these methods we utilized data from a nested case-control
      study examining repeated measures of urinary phthalate metabolites during
      pregnancy in association with preterm birth. RESULTS: The methods summarized may
      be useful for: 1) Examining sensitive windows of exposure in association with an
      outcome; 2) Summarizing repeated measures to estimate the relationship between
      average exposure and an outcome; 3) Identifying acute exposures that may be
      relevant to the outcome; and 4) Understanding the contribution of temporal
      patterns in exposure levels to the outcome of interest. In the study of
      phthalates, changes in urinary metabolites over pregnancy did not appear to
      contribute significantly to preterm birth, making summary of average exposure
      across gestation optimal given the current design. CONCLUSIONS: The methods
      exemplified may be of great use in future epidemiologic research projects
      intended to: 1) Elucidate the complex relationships between environmental
      chemical exposures and preterm birth; 2) Investigate biological mechanisms in
      prematurity using repeated measures of maternal factors throughout pregnancy; and
      3) More generally, address the relationship between a longitudinal predictor and
      a binary, non-time-varying outcome.

PMID- 25619203
TI  - Exercise improves endothelial function: a local analysis of production of nitric
      oxide and reactive oxygen species.
AB  - This study aimed at investigating the acute effects of aerobic exercise on
      endothelium-dependent vasomotor function of rat aorta, as well as mechanisms
      involved in endothelial nitric oxide (NO) bioactivity. Wistar rats were assigned
      to either a resting control (C, n = 21) or acutely exercised (E, n = 21) groups
      (60 min, 55-60% of maximum speed). After exercise, thoracic aorta was excised and
      cut into rings. Two rings were promptly applied to evaluate vasomotor function
      and the rest of aorta was used for additional measurements. Acute exercise
      significantly improved maximum ACh-induced relaxation (C, 91.6 +/- 1.2 vs. E,
      102.4 +/- 1.7%, p < 0.001) and sensitivity to ACh (C, -7.3 +/- 0.06 vs. E, -7.3
      +/- 0.02 log M, p < 0.01), and was accompanied by significantly increases on
      serine1177 eNOS phosphorylation, reflecting its enhanced activation. However,
      acute exercise also enhanced both superoxide and hydrogen peroxide production, as
      assayed by dihydroethidium oxidation, lucigenin chemiluminescence and Amplex Red
      assays. We also provided evidence for Nox2 NADPH oxidase (Nox) activation through
      gp91dstat-mediated inhibition of superoxide signals. Enhanced arterial
      relaxations associated with acute exercise were nearly-completely prevented by
      catalase, suggesting a role for paracrine hydrogen peroxide. Despite increased
      detectable oxidant generation, cellular oxidative stress was not evident, as
      suggested by unaltered GSH:GSSG ratio and lipid hydroperoxides. Collectively,
      these results demonstrate that one bout of moderate aerobic exercise improves
      endothelial function by increasing NO bioavailability, while superoxide and
      hydrogen peroxide are generated in a controlled fashion.

PMID- 25619204
TI  - Structural insights into the broad substrate specificity of carboxypeptidase T
      from Thermoactinomyces vulgaris.
AB  - The crystal structures of carboxypeptidase T (CpT) complexes with phenylalanine
      and arginine substrate analogs - benzylsuccinic acid and (2
      guanidinoethylmercapto)succinic acid - were determined by the molecular
      replacement method at resolutions of 1.57 A and 1.62 A to clarify the broad
      substrate specificity profile of the enzyme. The conservative Leu211 and Leu254
      residues (also present in both carboxypeptidase A and carboxypeptidase B) were
      shown to be structural determinants for recognition of hydrophobic substrates,
      whereas Asp263 was for recognition of positively charged substrates. Mutations of
      these determinants modify the substrate profile: the CpT variant Leu211Gln
      acquires carboxypeptidase B-like properties, and the CpT variant Asp263Asn the
      carboxypeptidase A-like selectivity. The Pro248-Asp258 loop interacting with
      Leu254 and Tyr255 was shown to be responsible for recognition of the substrate's
      C-terminal residue. Substrate binding at the S1' subsite leads to the ligand
      dependent shift of this loop, and Leu254 side chain movement induces the
      conformation rearrangement of the Glu277 residue crucial for catalysis. This is a
      novel insight into the substrate selectivity of metallocarboxypeptidases that
      demonstrates the importance of interactions between the S1' subsite and the
      catalytic center. 

PMID- 25619205
TI  - Incidental lesions found in veterans referred to dermatology: the value of a
      dermatologic examination.
AB  - BACKGROUND: Few studies have evaluated the detection of incidental skin cancers.
      OBJECTIVE: We sought to evaluate the rate of incidental cutaneous malignancies in
      routine dermatology consults. METHODS: This was a retrospective chart review of
      all dermatology consults at the Minneapolis Department of Veterans Affairs
      Medical Center over 8.25 years. Inclusion criteria included an in-person clinic
      visit within 18 months of the initial consult date. Patients with an in-person
      skin examination by a dermatologist in the 18 months before consult date were
      excluded. RESULTS: Of 28,405 consults sent during the study period, 17,174 met
      inclusion criteria. In all, 2257 (13.1%) patients had 1 or more biopsied
      incidental lesions. Half (50.3%; n = 1674) of the 3328 biopsied incidental
      lesions were malignant, which included 1187 patients. The per-person detection
      rate for an incidental malignant lesion was 6.9% (1187/17,174). There were 87
      incidental melanomas identified in 84 patients. The per-person detection rate for
      an incidental melanoma was 0.5% (84/17,174). The most frequent anatomical
      location for biopsied incidental malignancies was the head and neck (53.9%).
      Incidental melanomas were most frequently located on the back (33.3%).
      LIMITATIONS: Nondiverse patient population and conservative detection rate
      estimates are limitations. CONCLUSION: An in-person skin examination by a trained
      dermatologist is important for detection of skin malignancies. This may have
      implications for teledermatology.

PMID- 25619206
TI  - Does wound eversion improve cosmetic outcome?: Results of a randomized, split
      scar, comparative trial.
AB  - BACKGROUND: Wound edge eversion has been hypothesized to improve aesthetic
      outcomes after cutaneous wound closure. Data supporting this assertion are
      sparse. OBJECTIVE: We sought to determine if wound eversion, achieved with
      interrupted subcuticular sutures, improves aesthetic outcome compared with planar
      closures. METHODS: We undertook a prospective, randomized, split-scar
      intervention in patients who underwent cutaneous surgery. Half of the wound was
      randomized to an everted or planar repair; the other side received the opposite
      one. At 3- and 6-month follow-up, both the patient and 2 blinded observers
      evaluated the wound using the Patient Observer Self-Assessment Scale (POSAS).
      RESULTS: The total observer POSAS score for the everted (13.59, 12.26) and planar
      (12.91, 12.98) sides did not differ significantly at 3 or 6 months, respectively.
      Similarly, there was not a significant difference in patient assessment between
      the everted (16.23, 12.84) and planar (15.07, 12.79) sides at 3 or 6 months,
      respectively. Finally, there was no significant difference between the 2 closure
      methods in terms of scar height or width at follow-up. LIMITATIONS: This was a
      single-center trial, which used a validated but still subjective scar assessment
      instrument. CONCLUSION: Wound eversion was not significantly associated with
      improved overall scar assessments by blinded observers or patient assessment.

PMID- 25619207
TI  - Development of modularity in the neural activity of children's brains.
AB  - We study how modularity of the human brain changes as children develop into
      adults. Theory suggests that modularity can enhance the response function of a
      networked system subject to changing external stimuli. Thus, greater cognitive
      performance might be achieved for more modular neural activity, and modularity
      might likely increase as children develop. The value of modularity calculated
      from functional magnetic resonance imaging (fMRI) data is observed to increase
      during childhood development and peak in young adulthood. Head motion is
      deconvolved from the fMRI data, and it is shown that the dependence of modularity
      on age is independent of the magnitude of head motion. A model is presented to
      illustrate how modularity can provide greater cognitive performance at short
      times, i.e. task switching. A fitness function is extracted from the model.
      Quasispecies theory is used to predict how the average modularity evolves with
      age, illustrating the increase of modularity during development from children to
      adults that arises from selection for rapid cognitive function in young adults.
      Experiments exploring the effect of modularity on cognitive performance are
      suggested. Modularity may be a potential biomarker for injury, rehabilitation, or
      disease. 

PMID- 25619209
TI  - [Adopting and implementing a One Health approach for solving complex health
      problems].

PMID- 25619208
TI  - The natural history of conducting and reporting clinical trials: interviews with
      trialists.
AB  - BACKGROUND: To investigate the nature of the research process as a whole, factors
      that might influence the way in which research is carried out, and how
      researchers ultimately report their findings. METHODS: Semi-structured
      qualitative telephone interviews with authors of trials, identified from two
      sources: trials published since 2002 included in Cochrane systematic reviews
      selected for the ORBIT project; and trial reports randomly sampled from 14,758
      indexed on PubMed over the 12-month period from August 2007 to July 2008.
      RESULTS: A total of 268 trials were identified for inclusion, 183 published since
      2002 and included in the Cochrane systematic reviews selected for the ORBIT
      project and 85 randomly selected published trials indexed on PubMed. The response
      rate from researchers in the former group was 21% (38/183) and in the latter
      group was 25% (21/85). Overall, 59 trialists were interviewed from the two
      different sources. A number of major but related themes emerged regarding the
      conduct and reporting of trials: establishment of the research question;
      identification of outcome variables; use of and adherence to the study protocol;
      conduct of the research; reporting and publishing of findings. Our results reveal
      that, although a substantial proportion of trialists identify outcome variables
      based on their clinical experience and knowing experts in the field, there can be
      insufficient reference to previous research in the planning of a new trial. We
      have revealed problems with trial recruitment: not reaching the target sample
      size, over-estimation of recruitment potential and recruiting clinicians not
      being in equipoise. We found a wide variation in the completeness of protocols,
      in terms of detailing study rationale, outlining the proposed methods, trial
      organisation and ethical considerations. CONCLUSION: Our results confirm that the
      conduct and reporting of some trials can be inadequate. Interviews with
      researchers identified aspects of clinical research that can be especially
      challenging: establishing appropriate and relevant outcome variables to measure,
      use of and adherence to the study protocol, recruiting of study participants and
      reporting and publishing the study findings. Our trialists considered the
      prestige and impact factors of academic journals to be the most important
      criteria for selecting those to which they would submit manuscripts.

PMID- 25619210
TI  - [Emerging adenovirus threats: should China develop a vaccine-oriented prevention
      strategy?].

PMID- 25619211
TI  - [The epidemic situation and prevention countermeasures of brucellosis in China].

PMID- 25619212
TI  - [Prevalent status of heamorrhage fever with renal syndrome and immunization
      strategy in China].

PMID- 25619213
TI  - [Antibody persistence following booster vaccination with three doses of hepatitis
      B vaccines among low-response adults in Zhangqiu county of Shandong province: 24
      month of follow-up from 2009].
AB  - OBJECTIVE: To assess the 24-month efficacy after booster vaccination with 3 doses
      of hepatitis B vaccine among low-response adults in Zhangqiu county of Shandong
      province. METHODS: A total of 24 237 adults aged 18-49 years old, never received
      HepB vaccination, without HBV infection history, and had been living at 3 towns
      of Zhangqiu county in Shandong province for more than half a year in september,
      2009, were collected blood samples of 3-5 ml. A total of 11 590 adults who were
      negative for hepatitis B virus (HBV) surface antigen (HBsAg) , antibody to HBsAg
      (Anti-HBs) and antibody to HBV core antigen (Anti-HBc), were divided into four
      groups randomly and were vaccinated following the schedule of 0-1-6 with 20 ug
      hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in
      Saccharomyces cerevisiae (HepB-SC), 20 ug hepatitis B vaccine made by Chinese
      hamster ovary cell (HepB-CHO), 10 ug HepB-SC and 10 ug hepatitis B vaccine made
      by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB
      HP), respectively. The adults who were low-response to the primary hepatitis B
      vaccination (10 mU/ml <= anti-HBs<100 mU/ml) were divided into four groups by
      cluster random sampling. These groups were revaccinated with 3-dose of above
      mentioned four kinds of HepB respectively. Blood samples were drawn from 1 month
      (T1) and 24 month (T24) after the 3 dose revaccination, respectively. Anti-HBs
      and anti-HBc was detected by Chemiluminescence Microparticle Imunoassay (CMIA).
      RESULTS: Out of the 8 592 adults who have accepted the primary vaccination of
      hepatitis B and been collected the blood samples, 1 306 subjects showed low
      response. A total of 718 low-response subjects were collected blood samples after
      T1 and T24 following 3 doses of booster vaccination. The proportion of the four
      groups was 32.3% (232/718), 25.8% (185/718) , 19.3% (139/718) , 22.6% (162/718) ,
      respectively. The average proportion of anti-HBs >= 100 mIU/ml were decreased
      from 77.58% after T1 to 35.63% after T24 (chi2 = 256.87, P < 0.01). The
      proportion of anti-HBs >= 100 mIU/ml in T24 were 38.8% (90/177), 39.5% (73/185),
      25.2% (35/139) and 35.8% (58/162) in four groups, respectively. The proportion of
      anti-HBs>100 mIU/ml in T24 was significantly different among groups (chi2 = 8.81,
      P = 0.032). The average geometric mean concentration (GMC) was significantly
      reduced from 443.53 mIU/ml after T1 to 48.98 mIU/ml after T24 (F = 439.41, P <
      0.01). The GMC was 60.26 (45.71-77.62), 1.29 (38.90-69.18) , 35.48 (25.70-48.98)
      and 46.77 (33.88-6.07) mIU/ml in four groups, respectively (F = 1.97, P = 0.117)
      . Compared with vaccinated 20 ug HepB-SC, the proportion of anti-HBs >= 100
      mIU/ml and GMC was 0.56 (0.35-0.91) and -0.20 (-0.39--0.02) times. The positive
      of HBsAg was not found and the positive rate of anti-HBc was 2.6% (18/692) in
      T24. CONCLUSION: Protective antibody following booster vaccination with three
      doses of hepatitis B vaccines among low-response adults after 2 years fade
      faster. Antibody level of anti-HBs in T24 was corrected with the booster vaccine
      type and age. 20 ugHepB-SC seemed better than 10 ug HepB-SC.

PMID- 25619214
TI  - [Analysis of protective effect of using chickenpox live attenuated vaccine among
      4-17 years old children in Minhang district, Shanghai].
AB  - OBJECTIVES: To survey on the vaccination of varicella live attenuated vaccine
      among 4-17 children in Minhang District, and analyze the protective effect
      against varicella. METHODS: We collected outbreak chickenpox cases reported from
      infectious disease report system and surveillance units in Minhang district from
      1st May in 2012 to 30th Apr in 2013. The 1: 3 matched case-control study was
      conducted to questionnaire the legal guardian of the cases and control group, and
      calculate the protective effect and effective term of protection. The survey
      included vaccination, chickenpox exposure history, previous history of varicella
      illness, suffering from the symptoms of chickenpox, the vaccinations brand, etc.
      The criteria of accepted case were those healthy students who were in the same
      class with those chickenpox cases. The accepted matched controlling data were
      those children who were from the same class with outbreak chickenpox cases
      without varicelliform eruption, similar live condition, the closest house, the
      same gender, the closest age. This study investigated 390 cases of patients and
      the control group included 1 170 cases. Chi-square test was used to compare the
      vaccination of cases and controls, as well as the incidence of chickenpox
      vaccination different brands VarV, Mantel-Haenzel chi-square test was applied to
      compare the protective effect of the two groups. RESULTS: VarV overall
      vaccination rate was 68.3% (1 065/1 560), among them, the case group coverage was
      45.1% (176/390), significantly lower than the control group (76.0% (889/1 170))
      (chi2 = 128.55, P < 0.01). The coverage in children of 4-10 years old group was
      88.4% (375/424), significantly higher than the 11-17 years old group (60.7%
      (690/1 136)) (chi2 = 109.40, P < 0.01). The overall protective effect of VarV was
      78.10% (71.82%-82.98%).Vaccinated group incidence ratio was 16.5% (176/1 065),
      significantly lower than the unvaccinated group (43.2% (214/495)) (chi2 = 128.55,
      P < 0.01). The chickenpox risk of the children who were vaccinated was lower than
      those who were not, and the OR (95%CI) was 0.22(0.17-0.28) . Proportion of the
      fever and the typical symptoms of varicella zoster were 26.1% (46/176), 8.0%
      (14/176) in the children vaccinated VarV, significantly lower than children
      without VarV vaccination history (54.7% (117/214) , 18.2% (39/214) ) (chi2 values
      were 32.33 and 8.67, respectively. P values both <0.01). The varicella incidence
      was 17.4% (139/797) in children vaccinated domestic VarV, and it was 13.8%
      (37/268) in the group of imported VarV (chi2 = 1.92, P = 0.184) . The average
      duration of effective protection period for domestic and imported VarV was (6.2
      +/- 2.7), (6.3 +/- 3.4) years (F = 2.24, P = 0.136). CONCLUSIONS: The risk of
      varicella incidence and the proportion of fever or typical varicella zoster were
      lower in the one dose of VarV vaccinated; Effective protective effect was
      consistent in the children with domestic or imported VarV vaccination.

PMID- 25619215
TI  - [A study on the epidemic of pneumonia among children in Ningbo City, Zhejiang
      province, 2009-2012].
AB  - OBJECTIVE: To analyze the epidemiological characteristics and the bacterial
      pathogen composition of pneumonia among children under 5 years old in Ningbo.
      METHODS: In 2013 February-April, we selected pediatric ward in three hospitals
      according to stratified cluster random sampling, and from which we collected all
      57 556 hospitalized cases in January 2009-December 2012 period of children under
      5 years old. A total of 16 740 medical records and bacterial spectrum records of
      pneumonia or bronchial pneumonia cases among children under 5 years old were
      described to calculate the proportions of children pneumonia or bronchial
      pneumonia hospitalized cases accounted for hospitalized children over the same
      period(referred to as proportions of pneumonia incidence), the detection rate of
      bacterial pathogens, proportions of bacterial spectrum, and to analyze the
      characteristics and bacterial pathogen composition of pneumonia among children
      under 5 years. RESULTS: The proportions of children pneumonia in 2009-2012 were
      26.16% (2 882/11 017), 31.23% (4 004/12 819), 29.35% (4 898/16 689) and 29.10% (4
      956/17 031)(Z = 3.13, P < 0.01), and were in a downward trend by the increasing
      of age(Z = -113.74, P < 0.01). The proportions of children pneumonia of 0-5 age
      group were 50.71% (6 756/13 318), 26.60% (3 159/11 877), 24.17% (2 574 /10 648),
      22.36% (2 509 /11 223) and 16.63% (1 745 /10 490). The proportions of children
      pneumonia with different season were 26.90% (3 725/13 850), 26.51% (3 788/14
      287), 29.59% (4 442/15 011) and 33.21% (4 785 /14 408) (chi2 = 198.77, P < 0.01).
      The proportions of severe children pneumonia of 0-5 age group were 1.10% (74/6
      753), 0.47% (15/3 159), 0.19% (5 /2 574),0.08% (2 /2 509) and 0.06% (1 /1 745),
      with a downward trend by the age(F = 57.62, P < 0.01). The detection rate of
      Klebsiella pneumoniae, Haemophilus influenzae,Acinetobacter baumannii,
      Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae was 19.3%
      (540/2 805), 16.4% (460/2 805), 13.6% (381/2 805), 11.9% (335/2 805), 11.5%
      (323/2 805) and 6.8% (192/2 805). CONCLUSION: In 2009-2012, the proportions of
      children pneumonia under 5 year old constituted a relatively high proportion in
      Ningbo city. Children under 1 year old were the major suffering group of
      pneumonia and severe pneumonia, which should be the key prevention group. The
      major bacterial pathogens of children's pneumonia in Ningbo are gram-negative
      bacteria.

PMID- 25619216
TI  - [An analysis of high risk behaviors among female sex workers in Yunnan province
      in 2013].
AB  - OBJECTIVE: To understand the high risk behaviors of female sex workers (FSWs) in
      Yunnan province in 2013. METHODS: A cross-sectional investigation was conducted
      during April to June, 2013 in Yunnan province, census was used to the
      investigation where the number of FSWs was close to 200, while probability
      sampling was used where the number of FSWs was obviously over 200. A total of 25
      574 cases were investigated, and data on demography and risk behaviors were
      obtained by questionnaires one by one. RESULTS: A total of 25 574 cases were
      investigated, AIDS awareness among FSWs in high-level places, middle-level places
      and low-level place were 98.8% (92/7 401), 98.6% (150/10 995), and 96.0% (281/6
      655). FSWs from low-level place had a lower rate than those from the other two
      types of places (P < 0.01). The rate of condom use each time when having sex with
      clients within the recent one month among FESs from high-level places, middle
      level places and low-level place were 93.4% (6 307/6 755), 93.8% (10 109/10 782)
      and 90.4% (6 053/6 697), and the FSWs working in low-level place had a lower rate
      than those from the other two types of places(P < 0.01). Multi-factor logistic
      regression analysis showed that the following had a lower rate of condom use: the
      FSWs working in low-level place (OR = 1.56, 95% CI:1.36-1.79; OR = 1.36, 1.16
      1.59), over 30 years old (OR = 0.77, 95%CI:0.69-0.85), Yunnan citizen (OR = 0.88,
      95% CI:0.77-1.00), minority (OR = 1.32, 95% CI:1.16-1.50), under senior high
      school (OR = 0.61, 95%CI:0.49-0.75), married (OR = 0.81, 95% CI:0.71-0.92),
      living together (OR = 0.70, 95% CI:0.51-0.96), divorced or lost spouses (OR =
      0.81, 95% CI:0.65-1.02), worked less than 6 months in local areas (OR = 1.74, 95%
      CI:1.34-2.27), drug users (OR = 1.65, 95% CI:1.11-2.46), had not accepted HIV
      interventions (OR = 2.91, 95% CI:2.36-3.58), had no knowledge about AIDS (OR =
      4.50, 95% CI:3.48-5.82). The main reasons for not using condoms were the clients'
      unwilling to use, which accounted for 47.62% (270/567). The total rate of drug
      use was 1.0% (264/25 567) and the FSWs working in middle-level places had the
      highest rate of injecting drugs, which accounted for 0.6% (70/11 141). The FSWs
      working in low-level places had a higher rate than those who worked in high-level
      places and middle-level places in venereal diseases, which accounted for 1.2%
      (85/6 934) (P < 0.01). The rate of receiving effective interventions was 96.7%
      (24 717/25 574), the rate of accepting treatment and clean needles among drug
      users was 21.6% (57/264). CONCLUSION: High risk behaviors were serious among the
      FSWs who worked in low-level places, especially among the olders, the minorities,
      people who had lower educational level, the new-comer and drug users, which
      indicated that more attention needs to be paid among these populations.

PMID- 25619217
TI  - [Compare the application of flexible spatial statistics and kulldorff scanning
      window statistics to spatial aggregation of Hepatitis A].
AB  - OBJECTIVE: To compare the application valuable of flexible spatial scan
      statistics and kulldorff scanning window in the cluster detection and early
      warning of hepatitis A. METHODS: The case numbers and incidence data of hepatitis
      A in 2012 for all the counties (cities, districts)in Yunnan province were
      collected from China Information System for Disease Control and Prevention and
      the total number was 1 335. By extracting the time length by month, the flexible
      spatial scan statistics was tested by retrospective analyses of hepatitis A data
      in Yunnan in 2012 and compared the results with the Kulldorff circular scan
      statistic analyses. RESULTS: The results of flexible scanning window showed that
      there were fifteen hepatitis A spatial clusters in Yunnan province in 2012 and in
      July, these areas including Gejiu county, Mengzi county and Wenshan county had
      the strongest clusters (the log likelihood ratio (LLR) = 52.66, P = 0.001). The
      results of Kulldorff scanning window showed that there were twenty hepatitis A
      spatial clusters and these areas including Gejiu county, Hekou county, Maguan
      county, Mengzi county, Pingbian county, Wenshan county had the strongest clusters
      (LLR = 47.82, P = 0.001). The results of the flexible scanning window were the
      same as the actual monitoring results. But the results of Kulldorff scanning
      window showed that in May and June some areas without incidence had the clusters.
      CONCLUSION: Flexible scanning window can detect the monthly clusters of the
      Hepatitis A. Flexible scanning window had a higher accuracy than Kulldorff
      irregular circular scanning window. Flexible spatial scan statistics had the
      value in the use of spatial aggregation detecting on hepatitis A.

PMID- 25619218
TI  - [Levels for toxaphene in three categories of animal originated food in Pearl
      River Delta area].
AB  - OBJECTIVE: To explore the present contamination status and profile of toxaphene
      in fish, chicken and meat samples in Pearl River Delta area. METHODS: Totally 60
      independent samples including fish, chicken, meat were collected from
      Huizhou,Guangzhou,Dongguan,Jiangmen of Pearl River Delta area in Guangdong by
      purposive sampling from Oct 2010 to Jun 2011. Toxaphene monomer Parlar26,
      Parlar50 and Parlar62 levels in three various categories of foods were
      quantitatively and qualitatively analyzed referencing international authoritative
      standard methods by utilizing isotope dilution high-resolution gas
      chromatography/high-resolution double-focusing magnetic mass spectrometry (HRGC
      HRMS). The levels of pollution and characteristics were compared. RESULTS: The
      concentration of toxaphene median(M) in fish, chicken and meat were 12.87, 5.8
      and 1.89 ng/kg (gross weight) , respectively and the difference was significant(H
      = 14.29, P = 0.001). The toxaphene level in seafish (M = 32.07 ng/kg) was
      significantly higher than that in freshwater fish (M = 10.63 ng/kg, Z = -2.52, P
      = 0.012). The profile analysis showed that Parlar50 and Parlar26 were the
      predominant characteristic monomers in fish, which contributed about 44%
      (9.91/22.60, ng/kg) and 39% (8.89/22.60, ng/kg) to total concentration, and
      Parlar62 and Parlar26 were the two predominant congeners in poultry products, the
      two congeners accounted for 42% (5.03/11.90, ng/kg) and 38% (4.58/11.90, ng/kg).
      Furthermore Parlar26 and Parlar62 made up about 57% (3.45/6.08, ng/kg) and 26%
      (1.58/6.08, ng/kg) of total concentration in livestock meat respectively.
      CONCLUSION: Toxaphene levels in all tested food samples are far lower than the
      limited standard stipulated by the European Food Safety Authority (EFSA) in 2002,
      which was 0.1 mg/kg. The congener characteristic difference in the three
      categories food indicated that the different enrichment ability in Toxaphene in
      different animal species.

PMID- 25619219
TI  - [The association study between Eppin gene polymorphisms and idiopathic male
      infertility].
AB  - OBJECTIVE: To explore the correlation between four tagSNPs of Eppin gene
      (rs6124715, rs2231829, rs2227290 and rs11594) and the risk of idiopathic male
      infertility in the Chinese Han population. METHODS: A total of 473 confirmed
      infertile patients (from March 2005 to March 2007) and 198 fertile male controls
      (March 2005 to February 2009) were selected from two hospitals in Nanjing. All
      the subjects were Han Chinese and came from Nanjing or its surrounding areas. 5
      ml peripheral blood was drawn from each subject with informed consent. Four
      tagSNPs (rs6124715, rs2231829, rs2227290 and rs11594) in Eppin gene were analyzed
      by the PCR-restriction fragment length polymorphisms (PCR-RFLP) method. The serum
      testosterone level was evaluated by radioimmunoassay (RIA). RESULTS: The genotype
      frequencies of AA,AC and CC at rs11594 were 76.3% (361/473), 20.1% (95/473) and
      3.6% (17/473) respectively in the case group, while the frequencies in the
      control group were 75.3% (149/198), 24.2% (48/198), 0.5% (1/198) respectively,
      the differences were statistically significant (chi2 = 7.73, P = 0.021), the CC
      genotype carriers had an increased risk of male infertility (OR = 7.02, 95%
      CI:0.93-53.19). In the combined genotype analysis, the haplotype CTGA carriers
      has significantly lower onset risk (OR = 0.18, 95% CI:0.06-0.53). In the two
      groups, the frequencies and the risk of male infertility were no statistically
      significant in rs6124715, rs2231829 and rs2227290 genotype. CONCLUSIONS: The
      Eppin gene polymorphisms were correlated to the susceptibility to idiopathic male
      infertility. Among them, CC genotype at rs11594 could increase the risk of
      idiopathic male infertility.

PMID- 25619220
TI  - [The differences between three distinct locations of colorectal cancers based on
      clinicopathological characteristics and molecular features].
AB  - OBJECTIVE: To investigate the differences of clinical characteristics and
      molecular features among colorectal cancer subsides and provide evidence for
      colorectal cancer protection, diagnosis and treatment. METHODS: All of 4 316
      colorectal patients from Shanghai cancer center were selected for clinical
      character analysis, among which, 2 224 subjects for molecular feature analysis.
      Clinic pathological characteristics like age, gender, tumor types, histological
      types, differentiation and T-stage, as well as molecular features like hMLH1,
      hMSH2, CD44, p21, p53, COX2,E-cadherin, Her2 and Ki-67, were involved into this
      research. RESULTS: It showed that compared with left-sided colon and rectal
      cancers, right-sided cancers occurred more in women (46.0% (541/1 176); 39.2%
      (424/1 083); 41.2% (848/2 057), respectively, chi2 = 11.85, P < 0.01), had more
      mucinous or signet-ring carcinoma (12.0% (128/1 064), 5.8% (56/960), 4.0% (75/1
      859), respectively, chi2 = 31.27, P < 0.01), poor differentiated carcinoma (32.1%
      (343/1 069), 19.5% (201/1 033), 19.3% (380/1 967), respectively, chi2 = 72.66, P
      < 0.01) , and advanced T stage (87.9% (992/1 129), 83.2% (869/1 045), 72.2% (1
      486/2 057), respectively, chi2 = 121.44, P < 0.01). Meanwhile, the rates of hMLH1
      were higher in right-sided colon cancers when compared with rectal cancers (13.4%
      (59/439) vs 8.5% (88/1 035), OR (95%CI): 1.67 (1.18-2.37)), as well as the rates
      of hMSH2 negative expression (4.9% (22/452) vs 2.4% (26/1 083), OR (95% CI):
      2.08(1.17-3.71)). The rates of p53 positive expression were higher in right-sided
      colon cancers when compared with rectal cancers (76.2% (321/421) vs 68.4%, (776/1
      134), OR (95% CI): 0.68 (0.52-0.87)). Compared with right-sided colon cancers,
      the rates of Her2 positive expression were higher in rectal cancers (19.3%
      (176/913) vs 13.2% (45/340), OR (95% CI): 1.57 (1.10-2.23)) , as well as the
      rates of Ki-67 expression which was positive in more than 50% cells (73.6% (840/1
      141) vs 65.6% (299/456), OR (95% CI): 0.68 (0.54-0.86)). CONCLUSION: There are
      specific characteristics in right-sided colon cancers. The difference of
      molecular features between right-sided colon and rectal cancers are more
      significant.

PMID- 25619222
TI  - [The association between eating out of home and overweight/obesity among Chinese
      adults].
AB  - OBJECTIVE: To investigate the association between out-of-home eating (OH eating)
      and overweight/obesity among adults in China. METHODS: A total of 33 828 subjects
      aged 18-60 years old from the 2002 China National Nutrition and Health Survey
      were selected to calculate their daily consumption of food and nutrition, when
      people eating at home or out-of-home. The 24-hour dietary recall method for 3
      consecutive days was used to collect food intake information ( not including the
      condiment intake). The logistic regression method was used to analyze the
      relationship between OH eating and overweight/obesity. RESULTS: The prevalence of
      OH eating among Chinese adults aged 18-60 years old was 28.3% (9 562/33 828) in
      2002. Overall, the prevalence of OH eating was significantly greater among men
      compared to women (P < 0.05) , and the rate for men was 32.4% (5 117/15 805), and
      the rate for women was 24.7% (4 445/18 023). Besides, men who ate out of home
      showed a higher prevalence of overweight and obesity than those who ate at home
      (P < 0.05) , and the prevalence of overweight and obesity among them were 38.9%
      (1 991/5 117) and 31.7% (3 389/10 684), respectively. While women who ate at home
      showed a higher prevalence of overweight and obesity than those who ate out of
      home, and the prevalence of overweight and obesity among them were 38.1% (5
      174/13 571) and 35.6% (1 581/4 445), respectively. Compared with at-home eating
      group, 130.4 kJ energy, 12.2 g fat, 6.2 g protein and 67.1 mg sodium were
      excessively consumed per day for men, and 102.5 kJ energy, 8.6 g fat, 3.4 g
      protein and 60.6 mg sodium were excessively consumed per day for women. To sum
      up, OH eating was positively associated with overweight and obesity among men (OR
      = 1.18, 95% CI:1.09-1.27) , but not among women (OR = 0.94, 95% CI:0.87-1.01).
      CONCLUSION: OH eating was positively associated with overweight and obesity among
      men in China.

PMID- 25619221
TI  - [Case-control studies of the relevant factors among Ningxia Hui and Han prostate
      cancer groups].
AB  - OBJECTIVE: To explore the relationship between the relevant factors and prostate
      cancer among Hui and Han populations. METHODS: The study involved 267 prostate
      cancer patients as cases (214 cases from Han population and 53 cases from Hui
      population) and 534 prostatic hyperplasia patients as controls (428 cases from
      Han population and 106 cases from Hui population). All the patients were
      collected from the General Hospital of Ningxia Medical University during January
      of 2007 to September of 2013. The level of fasting blood glucose (FBG), total
      cholesterol (TC), triglyceride (TG), total prostate specific antigen (T-PSA),
      free prostate specific antigen (F-PSA) and free/total prostate specific antigen
      (F/T-PSA) were collected from the clinical medical records of the patients. Data
      were analyzed by the conditional logistic regression method, and attributable
      risk proportion(ARP) was calculated. RESULTS: In Hui population, the risk of
      prostate cancer for drinkers was 20.48 times higher than the non-drinkers (35.8%
      (19/53) to 5.7% (6/106), OR = 20.48, 95% CI: 4.95-84.66). The high level of F-PSA
      significantly increased the risk of prostate cancer for Hui group (83.0% (44/53)
      to 55.7% (59/106), OR = 4.27, 95%CI: 1.18-15.43). In contrast, the high TG level
      decreased the risk of prostate cancer for Hui group (18.9% (10/53) to 20.8%
      (22/106), OR = 0.24, 95% CI: 0.07-0.83). In Han population, the risk of prostate
      cancer for smokers was 1.89 times higher than the non-smokers (55.1% (118/214) to
      39.7% (170/428), OR = 1.89, 95% CI: 1.28-2.78). Either high level of T-PSA or F
      PSA increased the risk of prostate cancer for Han group (86.4% (185/214) to 53.7%
      (230/428),OR = 2.34, 95%CI:1.22-4.52;85.5% (183/214) to 56.1% (240/428), OR =
      2.43, 95% CI:1.29-4.59). However, the high TG level or high ratio of F/T-PSA
      decreased the risk of prostate cancer (15.4% (33/214) to 18.7% (80/428), OR =
      0.59, 95% CI:0.36-0.98; 53.3% (114/214) to 73.4% (314/428), OR = 0.53, 95%
      CI:0.36-0.78). The APRs of drinking and high level of F-PSA in Han populations
      were 66.6%, 62.4% in Hui populations , and the APRs of smoking and high level of
      T-PSA, high level of F-PSA were 33.8%, 71.3%, 67.3% in Han populations.
      CONCLUSION: Both drinking and high level of F-PSA might be the risky factors of
      prostate cancer while the high TG level might be protective factor for Hui group.
      However, for Han population, smoking, high T-PSA level, and high F-PSA level
      might be risky factors for prostate cancer while the high TG level and high ratio
      of F/T-PSA might be protective factors. In summary, the clinical relevant factors
      of prostate cancer may play different roles between Hui and Han populations in
      Ningxia region.

PMID- 25619223
TI  - [Comparison of dietary survey, frequency and 24 hour urinary Na methods in
      evaluation of salt intake in the population].
AB  - OBJECTIVE: To compare the difference and correlation between dietary salt intakes
      assessed by 24 hours urinary Na method, food weighted record method and food
      frequency questionnaire method. METHODS: All 2 184 subjects aged 18 to 69 were
      selected by multi stage stratified cluster random sampling method in Shandong
      province in June to September, 2011. Dietary salt intakes were measured by 24
      hours urinary Na method, food weighted record method and food frequency
      questionnaire method. The information on gender, age, dining locations and labour
      intensity of members dining at home for 3 days were recorded. And the dietary
      habits were surveyed by questionnaire. RESULTS: Salt intakes were 14.0, 12.0 and
      10.5 g/d assessed by 24 hours urinary Na method, food weighted record method and
      food frequency questionnaire, respectively. Comparing with 24 hours urinary Na
      method, salt intakes assessed by food weighted record method and food frequency
      questionnaire method were 2.0 g (14.3% undervalued) and 3.4 g (24.3% undervalued)
      less, respectively. Comparing with 24 hours urinary Na method, the proportion of
      individuals with salt intake over-reported and under-reported were 42.4% (856/2
      020) and 55.3% (1 117/2 020) by food weighted record method, and were 20.7%
      (418/2 020) and 16.3% (329/2 020) by food frequency questionnaire method,
      respectively; the proportion of individuals with salt intakes within +/- 25% of
      24 hours urinary Na method were 36.9% (745/2 020) and 28.4% (574/2 020),
      respectively. Salt intakes assessed by 24 hours urinary method correlated
      significantly with both salt intakes assessed by food weighted record method and
      food frequency questionnaire method; the correlation coefficients were 0.13 and
      0.07, respectively. With the increasing of salt intakes by subjects' self
      judgment, salt intakes were all rising significantly using three survey methods.
      Salt intakes of three group population of light, moderate and partial taste salty
      were 13.6, 13.6 and 14.7 g/d by 24 hours urinary Na method (F = 0.47, P < 0.05);
      11.0, 12.0 and 12.7 g/d by food weighted record method (F = 5.83, P < 0.05), and
      9.3, 10.2 and 11.9 g/d by food frequency questionnaire method (F = 5.83, P <
      0.05), respectively. CONCLUSION: Comparing with 24 hours urinary method, food
      weighted record method and food frequency questionnaire method would undervalue
      dietary salt intake. Salt intake status can be more accurately assessed by
      adjusting the underestimation rate.

PMID- 25619224
TI  - [Study on the pulmonary inflammatory effects induced by inhalation exposure to
      nanoscale carbon black aerosol in mice].
AB  - OBJECTIVE: To explore the carbon black induced effects of lung morphology and pro
      inflammation in mice, based on the carbon black aerosol dynamic inhalation
      exposure model. METHODS: The carbon black aerosol generated by dynamic inhalation
      device was imported exposure chamber to mice. Scanning electron microscopy (SEM)
      and transmission electron microscopy (TEM) were used to observe the characters of
      carbon black. Sixty 9-week-old male BALB/c mice were randomly divided into two
      control groups, 7 d exposure group and 14 d exposure group. The numbers of four
      groups of animals were 15, respectively. Mice were exposed to carbon black in the
      inhalation chamber at (29.33 +/- 9.10) mg/m(3) for 6 h/d for continuous exposure
      7 d and 14 d, respectively. After 7 d and 14 d exposure, the mice were sacrificed
      after the last exposure for 24 h. Control mice were killed at 7 d and 14 d. The
      trachea, lungs, liver, kidneys, and spleen tissues were separated and weighted.
      Hematoxylin and eosin (HE) staining was used to observe pathological changes of
      lung by light microscopy. Pulmonary interleukin-8 (IL-8) expression was analyzed
      by immunohistochemistry. Transmission electron microscopy was used to observe the
      ultra structure of lung tissue. RESULTS: After 14 d exposure carbon black, the
      lung coefficient was increased in exposure group compared with control (0.61 +/-
      0.03 vs 0.79 +/- 0.06, t = 6.26, P < 0.01). The spleen coefficient were higher
      than control(0.39 +/- 0.04 vs 0.51 +/- 0.06, t = 4.23, P < 0.01) . Other organ
      coefficients were no significant difference between CB group and control
      group.Histopathology displayed carbon black particles were deposited in the
      alveoli and lung bronchial wall in 7 d and 14 d groups. The black carbon
      particles were deposited within the lung tissue of mice in 14 d group. There were
      cilia damage, serious damage to the alveolar wall, inflammatory cell infiltration
      and more hyperemia in 14 d group. Immunohistochemistry showed the level of IL-8
      in 7 d (0.272 +/- 0.011) and 14 d (0.422 +/- 0.065) exposure group were higher
      than control group in 14 d (0.188 +/- 0.041) , F = 31.89, P < 0.01. TEM showed
      that the lung tissue vision was clear and organelle integrity in the control
      group. The particles appeared in lung tissue macrophage lysosomes in exposure
      group, the electron density was consistent with the carbon black particles.
      CONCLUSION: The dynamic carbon black particles exposure can affect the lung and
      spleen coefficient, damage integrity of lung morphology and induce inflammation
      in mice.

PMID- 25619225
TI  - High-Resolution Metal Nanopatterning by Means of Switchable Block Copolymer
      Templates.
AB  - In this review, recent developments in the fabrication of hexagonal and parallel
      ordered arrays of metallic nanodomains on a substrate are described. We focus on
      the nanopatterning approach by means of switchable block copolymer thin films.
      This approach is highly advantageous, because it can lead to extremely regular
      patterns with metal subunits of only a few nanometers in diameter and center-to
      center distances of tens of nanometers. Hence, the resulting 1D or 2D periodic
      arrays of metal nanodots and nanowires on silicon substrates can be fabricated
      with extremely high unit densities and on very large areas. The templated
      deposition of presynthesized metal nanoparticles on functional block copolymers
      is described in detail. Current challenges are discussed and an outlook for
      further developments is given. 

PMID- 25619227
TI  - Spherical LDH-Ag degrees -montmorillonite heterocoagulated system with a pH
      dependent sol-gel structure for controlled accessibility of AgNPs immobilized on
      the clay lamellae.
AB  - Aqueous suspensions of spherical ZnMgAl-layered double hydroxides [LDH(sph)] and
      antibacterial silver nanoparticles (AgNPs) deposited on the lamellae of
      montmorillonite were used for the synthesis of composites, which behave like
      coherent gels at low pH (?4.5) and incoherent sols at higher pH (?4.5). The
      composition of the composite was chosen as LDH(sph)/Ag degrees -montm. = 25:75 wt
      % in order to ensure a sol-gel transition that can also be characterized by
      viscometry. This pH-sensitive heterocoagulated system consisting of oppositely
      charged colloid particles was suitable for the release of antimicrobial AgNPs
      immobilized on the clay lamellae via a pH-controlled gel-sol transition. The
      heterocoagulation process was also characterized by surface charge titration
      measurements. Spherical LDH/Ag degrees -montmorillonite composite samples were
      identified by X-ray diffraction (XRD) measurements. The morphological properties
      of the composites were studied, and the presence of the heterocoagulated
      structure was confirmed by scanning electron microscopy (SEM). The nanoscale
      structure of the LDH(sph)-Ag degrees -montmorillonite composite obtained was also
      verified by small-angle X-ray scattering (SAXS), and the rheological
      characteristics were studied at various pH values. The viscosity and yield value
      of the composite decreased by an order of magnitude upon increasing the pH from
      3.0 to 5.5. The sol-gel transition of the composite suspension was reversible in
      the previously mentioned pH range. 

PMID- 25619228
TI  - Water mobility and microstructure evolution in the germinating Medicago
      truncatula seed studied by NMR relaxometry. A revisited interpretation of
      multicomponent relaxation.
AB  - The water status of Medicago truncatula Gaertn. seed was followed by low-field
      NMR relaxometry during germination with and without oryzalin or fusicoccin used
      as growth modulators. T1 and T2 relaxation times and proportions P1 and P2 were
      determined on fresh, frozen, and freeze-thawed samples to characterize changes in
      water dynamics and compartmentation and in the nonfreezing water fraction. The
      results demonstrate that low-field NMR relaxometry allowed differentiating
      germination phases and events occurring during them as well as perturbations
      related to the presence of growth modulators. The results provide clear evidence
      that the classical multicomponent relaxation interpretation cannot directly
      relate T2 components and morphological compartments in biological tissue. 

PMID- 25619229
TI  - Effect of interior loop length on the thermal stability and pK(a) of i-motif DNA.
AB  - The four-stranded i-motif (iM) conformation of cytosine-rich DNA is important in
      a wide variety of biochemical systems ranging from its use in nanomaterials to a
      potential role in oncogene regulation. An iM is stabilized by acidic pH that
      allows hemiprotonated cytidines to form a C.C(+) base pair. Fundamental studies
      that aim to understand how the lengths of loops connecting the protonated C.C(+)
      pairs affect intramolecular iM physical properties are described here. We
      characterized both the thermal stability and the pK(a) of intramolecular iMs with
      differing loop lengths, in both dilute solutions and solutions containing
      molecular crowding agents. Our results showed that intramolecular iMs with longer
      central loops form at pHs and temperatures higher than those of iMs with longer
      outer loops. Our studies also showed that increases in thermal stability of iMs
      when molecular crowding agents are present are dependent on the loop that is
      lengthened. However, the increase in pK(a) for iMs when molecular crowding agents
      are present is insensitive to loop length. Importantly, we also determined the
      proton activity of solutions containing high concentrations of molecular crowding
      agents to ascertain whether the increase in pK(a) of an iM is caused by
      alteration of this activity in buffered solutions. We determined that crowding
      agents alone increase the apparent pK(a) of a number of small molecules as well
      as iMs but that increases to iM pK(a) were greater than that expected from a
      shift in proton activity.

PMID- 25619231
TI  - Clonal expansion of hepatocytes with a selective advantage occurs during all
      stages of chronic hepatitis B virus infection.
AB  - Hepatocyte clone size was measured in liver samples of 21 patients in various
      stages of chronic hepatitis B virus (HBV) infection and from 21 to 76 years of
      age. Hepatocyte clones containing unique virus-cell DNA junctions formed by the
      integration of HBV DNA were detected using inverse nested PCR. The maximum
      hepatocyte clone size tended to increase with age, although there was
      considerable patient-to-patient variation in each age group. There was an upward
      trend in maximum clone size with increasing fibrosis, inflammatory activity and
      with seroconversion from HBV e-antigen (HBeAg)-positive to HBeAg-negative, but
      these differences did not reach statistical significance. Maximum hepatocyte
      clone size did not differ between patients with and without a coexisting
      hepatocellular carcinoma. Thus, large hepatocyte clones containing integrated HBV
      DNA were detected during all stages of chronic HBV infection. Using laser
      microdissection, no significant difference in clone size was observed between
      foci of HBV surface antigen (HBsAg)-positive and HBsAg-negative hepatocytes,
      suggesting that expression of HBsAg is not a significant factor in clonal
      expansion. Laser microdissection also revealed that hepatocytes with normal
      appearing histology make up a major fraction of the cells undergoing clonal
      expansion. Thus, preneoplasia does not appear to be a factor in the clonal
      expansion detected in our assays. Computer simulations suggest that the large
      hepatocyte clones are not produced by random hepatocyte turnover but have an as
      yet-unknown selective advantage that drives increased clonal expansion in the HBV
      infected liver.

PMID- 25619232
TI  - Education and imaging. Gastrointestinal: multiple inflammatory myoglandular
      polyps in a single patient.

PMID- 25619233
TI  - Education and imaging. Gastrointestinal: botulinum toxin effective in refractory
      gastroparesis in paediatric practice.

PMID- 25619234
TI  - Education and imaging. Gastrointestinal: breast cancer metastasis to the
      esophagus diagnosed using endoscopic ultrasound-guided fine-needle aspiration.

PMID- 25619235
TI  - Education and imaging. Hepatology: "central dot sign" of Caroli syndrome.

PMID- 25619236
TI  - Education and imaging. Hepatology: pancreatic lymphoepithelial cyst mimicking
      mucinous cystic neoplasm.

PMID- 25619237
TI  - Mismatch in the distribution of floral ecotypes and pollinators: insights into
      the evolution of sexually deceptive orchids.
AB  - Plants are predicted to show floral adaptation to geographic variation in the
      most effective pollinator, potentially leading to reproductive isolation and
      genetic divergence. Many sexually deceptive orchids attract just a single
      pollinator species, limiting opportunities to experimentally investigate
      pollinator switching. Here, we investigate Drakaea concolor, which attracts two
      pollinator species. Using pollinator choice tests, we detected two
      morphologically similar ecotypes within D. concolor. The common ecotype only
      attracted Zaspilothynnus gilesi, whereas the rare ecotype also attracted an
      undescribed species of Pogonothynnus. The rare ecotype occurred at populations
      nested within the distribution of the common ecotype, with no evidence of
      ecotypes occurring sympatrically. Surveying for pollinators at over 100 sites
      revealed that ecotype identity was not correlated with wasp availability, with
      most orchid populations only attracting the rare Z. gilesi. Using microsatellite
      markers, genetic differentiation among populations was very low (GST = 0.011)
      regardless of ecotype, suggestive of frequent gene flow. Taken together, these
      results may indicate that the ability to attract Pogonothynnus has evolved
      recently, but this ecotype is yet to spread. The nested distribution of ecotypes,
      rather than the more typical formation of ecotypes in allopatry, illustrates that
      in sexually deceptive orchids, pollinator switching could occur throughout a
      species' range, resulting from multiple potentially suitable but unexploited
      pollinators occurring in sympatry. This unusual case of sympatric pollinators
      highlights D. concolor as a promising study system for further understanding the
      process of pollinator switching from ecological, chemical and genetic
      perspectives.

PMID- 25619238
TI  - Are nilotinib-associated vascular adverse events an under-estimated problem?
AB  - Vascular adverse events have been reported with nilotinib, a tyrosine kinase
      inhibitor prescribed for chronic myeloid leukaemia. However, few data specify
      their incidence, or whether they occur in predisposed patients. Hence, we
      prospectively studied 30 consecutive patients to assess the frequency of such
      adverse reactions and determine whether the patients presenting with these
      adverse events bear predisposing factors. From 3 to 73 months after nilotinib
      initiation, 10 of the 30 patients experienced vascular events. Three patients of
      these 10 were devoid of any patent cardiovascular risk factor, except for age.
      This study points out an occurrence more frequent than expected of vascular
      adverse events associated with nilotinib (> 30% vs. < 1% in summary of product
      characteristics), and particularly of vascular events of late onset in patients
      with no pre-existing risk factors. 

PMID- 25619239
TI  - Decoding genomes.
AB  - The primary sequence of DNA can be decoded a million times faster and cheaper
      than it could 20 years ago. This capability is transforming our understanding of
      biology and has stimulated efforts to influence modern medicine through routine
      sequencing of human genomes. I describe how Solexa-Illumina sequencing originated
      from our laboratory and was developed into widely used commercial sequencing
      platforms. I also discuss examples of how this approach is being employed to
      exploit genome sequencing for medicine. 

PMID- 25619240
TI  - Spatial gradients controlling spindle assembly.
AB  - The mitotic spindle is the macromolecular machine utilized to accurately
      segregate chromosomes in cells. How this self-organized structure assembles is a
      key aspect of understanding spindle morphogenesis. In the present review, we
      focus on understanding mechanisms of spindle self-assembly and address how
      subcellular signalling gradients, such as Ran-GTP and Aurora B, contribute to
      spindle organization and function. 

PMID- 25619230
TI  - Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body
      Donation Program.
AB  - The Brain and Body Donation Program (BBDP) at Banner Sun Health Research
      Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain
      only donations and currently has banked more than 1600 brains. More than 430
      whole-body donations have been received since this service was commenced in 2005.
      The collective academic output of the BBDP is now described as the Arizona Study
      of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are
      enrolled as cognitively normal volunteers residing in the retirement communities
      of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed
      at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median
      age at death is 82. Subjects receive standardized general medical, neurological,
      neuropsychological and movement disorders assessments during life and more than
      90% receive full pathological examinations by medically licensed pathologists
      after death. The Program has been funded through a combination of internal,
      federal and state of Arizona grants as well as user fees and pharmaceutical
      industry collaborations. Subsets of the Program are utilized by the US National
      Institute on Aging Arizona Alzheimer's Disease Core Center and the US National
      Institute of Neurological Disorders and Stroke National Brain and Tissue Resource
      for Parkinson's Disease and Related Disorders. Substantial funding has also been
      received from the Michael J. Fox Foundation for Parkinson's Research. The Program
      has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval
      for the entire collection. The median RNA Integrity Number (RIN) for frozen brain
      and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have
      been served and currently about 200 are served annually. These requests have been
      made by more than 400 investigators located in 32 US states and 15 countries.
      Tissue from the BBDP has contributed to more than 350 publications and more than
      200 grant-funded projects. 

PMID- 25619241
TI  - Centrosomes and mitotic spindle poles: a recent liaison?
AB  - Centrosomes comprise two cylindrical centrioles embedded in the pericentriolar
      material (PCM). The PCM is an ordered assembly of large scaffolding molecules,
      providing an interaction platform for proteins involved in signalling,
      trafficking and most importantly microtubule nucleation and organization. In
      mitotic cells, centrosomes are located at the spindle poles, sites where spindle
      microtubules converge. However, certain cell types and organisms lack
      centrosomes, yet contain focused spindle poles, highlighting that despite their
      juxtaposition in cells, centrosomes and mitotic spindle poles are distinct
      physical entities. In the present paper, we discuss the origin of centrosomes and
      summarize their contribution to mitotic spindle assembly and cell division. We
      then describe the key molecular players that mediate centrosome attachment to
      mitotic spindle poles and explore why co-segregation of centrosomes and spindle
      poles into daughter cells is of potential benefit to organisms. 

PMID- 25619242
TI  - Sharpening the anaphase switch.
AB  - The segregation of sister chromatids during mitosis is one of the most easily
      visualized, yet most remarkable, events during the life cycle of a cell. The
      accuracy of this process is essential to maintain ploidy during cell duplication.
      Over the past 20 years, substantial progress has been made in identifying
      components of both the kinetochore and the mitotic spindle that generate the
      force to move mitotic chromosomes. Additionally, we now have a reasonable, albeit
      incomplete, understanding of the molecular and biochemical events that are
      involved in establishing and dissolving sister-chromatid cohesion. However, it is
      less well-understood how this dissolution of cohesion occurs synchronously on all
      chromosomes at the onset of anaphase. At the centre of the action is the anaphase
      promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that, in association
      with its activator cell-division cycle protein 20 homologue (Cdc20), is
      responsible for the destruction of securin. This leads to the activation of
      separase, a specialized protease that cleaves the kleisin-subunit of the cohesin
      complex, to relieve cohesion between sister chromatids. APC/C-Cdc20 is also
      responsible for the destruction of cyclin B and therefore inactivation of the
      cyclin B-cyclin-dependent kinase 1 (Cdk1). This latter event induces a change in
      the microtubule dynamics that results in the movement of sister chromatids to
      spindle poles (anaphase A), spindle elongation (anaphase B) and the onset of
      cytokinesis. In the present paper, we review the emerging evidence that multiple,
      spatially and temporally regulated feedback loops ensure anaphase onset is rapid,
      co-ordinated and irreversible. 

PMID- 25619243
TI  - Functionality of the chromosomal passenger complex in cancer.
AB  - The evolutionary conserved chromosomal passenger complex (CPC) is essential for
      faithful transmission of the genome during cell division. Perturbation of this
      complex in cultured cells gives rise to chromosome segregation errors and
      cytokinesis failure and as a consequence the ploidy status of the next generation
      of cells is changed. Aneuploidy and chromosomal instability (CIN) is observed in
      many human cancers, but whether this may be caused by deregulation of the CPC is
      unknown. In the present review, we discuss if and how a dysfunctional CPC could
      contribute to CIN in cancer. 

PMID- 25619244
TI  - Retromer and sorting nexins in endosomal sorting.
AB  - The evolutionarily conserved endosomal retromer complex rescues transmembrane
      proteins from the lysosomal degradative pathway and facilitates their recycling
      to other cellular compartments. Retromer functions in conjunction with numerous
      associated proteins, including select members of the sorting nexin (SNX) family.
      In the present article, we review the molecular architecture and cellular roles
      of retromer and its various functional partners. The endosomal network is a
      crucial hub in the trafficking of proteins through the cellular endomembrane
      system. Transmembrane proteins, here termed cargos, enter endosomes by
      endocytosis from the plasma membrane or by trafficking from the trans-Golgi
      network (TGN). Endosomal cargo proteins face one of the two fates: retention in
      the endosome, leading ultimately to lysosomal degradation or export from the
      endosome for reuse ('recycling'). The balance of protein degradation and
      recycling is crucial to cellular homoeostasis; inappropriate sorting of proteins
      to either fate leads to cellular dysfunction. Retromer is an endosome-membrane
      associated protein complex central to the recycling of many cargo proteins from
      endosomes, both to the TGN and the plasma membrane (and other specialized
      compartments, e.g. lysosome-related organelles). Retromer function is reliant on
      a number of proteins from the SNX family. In the present article, we discuss this
      inter-relationship and how defects in retromer function are increasingly being
      linked with human disease. 

PMID- 25619245
TI  - Regulation of processive motion and microtubule localization of cytoplasmic
      dynein.
AB  - The cytoplasmic dynein complex is the major minus-end-directed microtubule motor.
      Although its directionality is evolutionary well conserved, differences exist
      among cytoplasmic dyneins from different species in their stepping behaviour,
      maximum velocity and force production. Recent experiments also suggest
      differences in processivity regulation. In the present article, we give an
      overview of dynein's motile properties, with a special emphasis on processivity
      and its regulation. Furthermore, we summarize recent findings of different
      pathways for microtubule plus-end loading of dynein. The present review
      highlights how distinct functions in different cell types or organisms appear to
      require different mechanochemical dynein properties and localization pathways. 

PMID- 25619246
TI  - Myosin tails and single alpha-helical domains.
AB  - The human genome contains 39 myosin genes, divided up into 12 different classes.
      The structure, cellular function and biochemical properties of many of these
      isoforms remain poorly characterized and there is still some controversy as to
      whether some myosin isoforms are monomers or dimers. Myosin isoforms 6 and 10
      contain a stable single alpha-helical (SAH) domain, situated just after the
      canonical lever. The SAH domain is stiff enough to be able to lengthen the lever
      allowing the myosin to take a larger step. In addition, atomic force microscopy
      and atomistic simulations show that SAH domains unfold at relatively low forces
      and have a high propensity to refold. These properties are likely to be important
      for protein function, enabling motors to carry cargo in dense actin networks, and
      other proteins to remain attached to binding partners in the crowded cell. 

PMID- 25619249
TI  - Kinesins in cell migration.
AB  - Human cells express 45 kinesins, microtubule motors that transport a variety of
      molecules and organelles within the cell. Many kinesins also modulate the tracks
      they move on by either bundling or sliding or regulating the dynamic assembly and
      disassembly of the microtubule polymer. In migrating cells, microtubules control
      the asymmetry between the front and rear of the cell by differentially regulating
      force generation processes and substrate adhesion. Many of these functions are
      mediated by kinesins, transporters as well as track modulators. In this review,
      we summarize the current knowledge on kinesin functions in cell migration. 

PMID- 25619248
TI  - Plant cytokinesis: a tale of membrane traffic and fusion.
AB  - Cytokinesis separates the forming daughter cells. Higher plants have lost the
      ability to constrict the plasma membrane (PM) in the division plane. Instead,
      trans-Golgi network (TGN)-derived membrane vesicles are targeted to the centre of
      the division plane and generate, by homotypic fusion, the partitioning membrane
      named cell plate (CP). The CP expands in a centrifugal fashion until its margin
      fuses with the PM at the cortical division site. Mutant screens in Arabidopsis
      have identified a cytokinesis-specific syntaxin named KNOLLE and an interacting
      Sec1/Munc18 (SM) protein named KEULE both of which are required for vesicle
      fusion during cytokinesis. KNOLLE is only made during M-phase, targeted to the
      division plane and degraded in the vacuole at the end of cytokinesis. Here we
      address mechanisms of KNOLLE trafficking and interaction of KNOLLE with different
      soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP)
      receptor (SNARE) partners and with SM-protein KEULE, ensuring membrane fusion in
      cytokinesis. 

PMID- 25619247
TI  - The myosin mesa and a possible unifying hypothesis for the molecular basis of
      human hypertrophic cardiomyopathy.
AB  - No matter how many times one explores the structure of the myosin molecule, there
      is always something new to discover. Here, I describe the myosin mesa, a
      structural feature of the motor domain that has the characteristics of a binding
      domain for another protein, possibly myosin-binding protein C (MyBP-C).
      Interestingly, many well-known hypertrophic cardiomyopathy (HCM) mutations lie
      along this surface and may affect the putative interactions proposed here. A
      potential unifying hypothesis for the molecular basis of human hypertrophic
      cardiomyopathy is discussed here. It involves increased power output of the
      cardiac muscle as a result of HCM mutations causing the release of inhibition by
      myosin binding protein C. 

PMID- 25619250
TI  - Pushing with actin: from cells to pathogens.
AB  - Actin polymerization is harnessed by cells to generate lamellipodia for movement
      and by a subclass of pathogens to facilitate invasion of their infected hosts.
      Using electron tomography (ET), we have shown that lamellipodia are formed via
      the generation of subsets of actin filaments joined by branch junctions. Image
      averaging produced a 2.9 nm resolution model of branch junctions in situ and
      revealed a close fit to the electron density map of the actin-related protein 2/3
      (Arp2/3)-actin complex in vitro. Correlated live-cell imaging and ET was also
      used to determine how actin networks are created and remodelled during the
      initiation and inhibition of protrusion in lamellipodia. Listeria, Rickettsia and
      viruses, such as vaccinia virus and baculovirus, exploit the actin machinery of
      host cells to generate propulsive actin comet tails to disseminate their
      infection. By applying ET, we have shown that baculovirus generates at its rear a
      fishbone-like array of subsets of branched actin filaments, with an average of
      only four filaments engaged in pushing at any one time. In both of these studies,
      the application of ET of negatively stained cytoskeletons for higher filament
      resolution and cryo-ET for preserving overall 3D morphology was crucial for
      obtaining a complete structure-function analysis of actin-driven propulsion. 

PMID- 25619251
TI  - Ypt1 and COPII vesicles act in autophagosome biogenesis and the early secretory
      pathway.
AB  - The GTPase Ypt1, Rab1 in mammals functions on multiple intracellular trafficking
      pathways. Ypt1 has an established role on the early secretory pathway in
      targeting coat protein complex II (COPII) coated vesicles to the cis-Golgi.
      Additionally, Ypt1 functions during the initial stages of macroautophagy, a
      process of cellular degradation induced during periods of cell stress. In the
      present study, we discuss the role of Ypt1 and other secretory machinery during
      macroautophagy, highlighting commonalities between these two pathways. 

PMID- 25619252
TI  - SEC16 in COPII coat dynamics at ER exit sites.
AB  - Protein export from the endoplasmic reticulum (ER), the first step in protein
      transport through the secretory pathway, is mediated by coatomer protein II
      (COPII)-coated vesicles at ER exit sites. COPII coat assembly on the ER is well
      understood and the conserved large hydrophilic protein Sec16 clearly has a role
      to play in COPII coat dynamics. Sec16 localizes to ER exit sites, its loss of
      function impairs their functional organization in all species where it has been
      studied, and it interacts with COPII coat subunits. However, its exact function
      in COPII dynamics is debated, as Sec16 is proposed to act as a scaffold to
      recruit COPII components and as a device to regulate the Sar1 activity in
      uncoating, in such a way that the coat is released only when the vesicle is fully
      formed and loaded with cargo. Furthermore, Sec16 has been shown to respond to
      nutrient signalling, thus coupling environmental stimuli to secretory capacity. 

PMID- 25619253
TI  - Procollagen export from the endoplasmic reticulum.
AB  - Collagens are secreted into the extracellular space where they assemble into a
      large complex protein network to form basement membrane and extracellular matrix.
      Collagens are therefore essential for cell attachment, tissue organization and
      the overall survival of all multicellular organisms. Collagens are synthesized in
      the endoplasmic reticulum (ER) but they are too big to fit into a conventional
      coat protein complex II (COPII) transport carrier of 60-90 nm average diameter.
      How are these molecules exported from the ER and then transported along the
      secretory pathway? We describe here the involvement of special packing machinery
      composed of hetero oligomers of transport and Golgi organization 1 (TANGO1) and
      cutaneous T-cell lymphoma-associated antigen 5 (cTAGE5) in the export of
      procollagen VII from the ER. 

PMID- 25619254
TI  - A small GTPase involved in mitochondrial morphology and function.
AB  - Mitochondria are the powerhouse of cells as they produce the bulk of ATP which is
      consumed by the cell. They form a highly interconnected network that is governed
      by fission and fusion processes. In addition, mitochondria and the endoplasmic
      reticulum (ER) are found in close proximity to each other and it is thought that
      they maintain contact sites to exchange molecules. The regulation and the
      function of these contact sites need to be further explored. The small GTPase
      Arf1 (ADP-ribosylation factor 1), which is best known for its essential role in
      the generation of coatomer protein I (COPI)-coated vesicles at the Golgi complex
      appears to be also essential for the dynamics and maintenance of mitochondrial
      function, presumably at ER-mitochondrial contact sites. 

PMID- 25619255
TI  - Function and interactions of the Ysc84/SH3yl1 family of actin- and lipid-binding
      proteins.
AB  - Understanding how actin filaments are nucleated, polymerized and disassembled in
      close proximity to cell membranes is an area of growing interest. Protrusion of
      the plasma membrane is required for cell motility, whereas inward curvature or
      invagination is required for endocytic events. These morphological changes in
      membrane are often associated with rearrangements of actin, but how the many
      actin-binding proteins of eukaryotes function in a co-ordinated way to generate
      the required responses is still not well understood. Identification and analysis
      of proteins that function at the interface between the plasma membrane and actin
      regulatory networks is central to increasing our knowledge of the mechanisms
      required to transduce the force of actin polymerization to changes in membrane
      morphology. The Ysc84/SH3yl1 proteins have not been extensively studied, but work
      in both yeast and mammalian cells indicate that these proteins function at the
      hub of networks integrating regulation of filamentous actin (F-actin) with
      changes in membrane morphology. 

PMID- 25619256
TI  - The roles of the oncoprotein GOLPH3 in contractile ring assembly and membrane
      trafficking during cytokinesis.
AB  - Cytokinesis is an intricate process that requires an intimate interplay between
      actomyosin ring constriction and plasma membrane remodelling at the cleavage
      furrow. However, the molecular mechanisms involved in coupling the cytoskeleton
      dynamics with vesicle trafficking during cytokinesis are poorly understood. The
      highly conserved Golgi phosphoprotein 3 (GOLPH3), functions as a
      phosphatidylinositol 4-phosphate (PI4P) effector at the Golgi. Recent studies
      have suggested that GOLPH3 is up-regulated in several cancers and is associated
      with poor prognosis and more aggressive tumours. In Drosophila melanogaster,
      GOLPH3 localizes at the cleavage furrow of dividing cells, is required for
      successful cytokinesis and acts as a key molecule in coupling phosphoinositide
      (PI) signalling with actomyosin ring dynamics. Because cytokinesis failures have
      been linked with pre-malignant disease and cancer, the novel connection between
      GOLPH3 and cytokinesis imposes new fields of investigation in cancer biology and
      therapy. 

PMID- 25619258
TI  - Drink or drive: competition between macropinocytosis and cell migration.
AB  - The cytoskeleton is utilized for a variety of cellular processes, including
      migration, endocytosis and adhesion. The required molecular components are often
      shared between different processes, but it is not well understood how the cells
      balance their use. We find that macropinocytosis and cell migration are
      negatively correlated. Heavy drinkers move only slowly and vice versa, fast cells
      do not take big gulps. Both processes are balanced by the lipid
      phosphatidylinositol 3,4,5-trisphosphate (PIP3). Elevated PIP3 signalling causes
      a shift towards macropinocytosis and inhibits motility by redirecting the
      SCAR/WAVE complex, a major nucleator of actin filaments. High resolution
      microscopy shows that patches with high levels of PIP3 recruit SCAR/WAVE on their
      periphery, resulting in circular ruffle formation and engulfment. Results shed
      new light on the role of PIP3, which is commonly thought to promote cell
      motility. 

PMID- 25619257
TI  - Fibronectin remodelling: cell-mediated regulation of the microenvironment.
AB  - The biophysical, mechanical and chemical characteristics of extracellular
      matrixes influence many cellular functions to control tissue homoeostasis and
      drive progression of cancer and inflammatory diseases. To maintain normal tissue
      function, fibronectin-rich matrixes are subject to dynamic cell-mediated
      structural and chemical modification. In this article, we discuss how localized
      application of mechanical force, heterodimer-specific integrin engagement and
      matrix proteolysis regulate fibronectin assembly and turnover. We also speculate
      that recently identified integrin trafficking, syndecan signalling and adhesion
      receptor-growth factor receptor cross-talk mechanisms might dynamically control
      the function, assembly and mechanical properties of a viable, and
      mechanoresponsive, fibronectin network. 

PMID- 25619259
TI  - Salt-inducible kinase 3 deficiency exacerbates lipopolysaccharide-induced
      endotoxin shock accompanied by increased levels of pro-inflammatory molecules in
      mice.
AB  - Macrophages play important roles in the innate immune system during infection and
      systemic inflammation. When bacterial lipopolysaccharide (LPS) binds to Toll-like
      receptor 4 on macrophages, several signalling cascades co-operatively up-regulate
      gene expression of inflammatory molecules. The present study aimed to examine
      whether salt-inducible kinase [SIK, a member of the AMP-activated protein kinase
      (AMPK) family] could contribute to the regulation of immune signal not only in
      cultured macrophages, but also in vivo. LPS up-regulated SIK3 expression in
      murine RAW264.7 macrophages and exogenously over-expressed SIK3 negatively
      regulated the expression of inflammatory molecules [interleukin-6 (IL-6), nitric
      oxide (NO) and IL-12p40] in RAW264.7 macrophages. Conversely, these inflammatory
      molecule levels were up-regulated in SIK3-deficient thioglycollate-elicited
      peritoneal macrophages (TEPM), despite no impairment of the classical signalling
      cascades. Forced expression of SIK3 in SIK3-deficient TEPM suppressed the levels
      of the above-mentioned inflammatory molecules. LPS injection (10 mg/kg) led to
      the death of all SIK3-knockout (KO) mice within 48 hr after treatment, whereas
      only one mouse died in the SIK1-KO (n = 8), SIK2-KO (n = 9) and wild-type (n = 8
      or 9) groups. In addition, SIK3-KO bone marrow transplantation increased LPS
      sensitivity of the recipient wild-type mice, which was accompanied by an
      increased level of circulating IL-6. These results suggest that SIK3 is a unique
      negative regulator that suppresses inflammatory molecule gene expression in LPS
      stimulated macrophages.

PMID- 25619261
TI  - Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses.
AB  - Citrate, a central component of cellular metabolism, is a widely used anti
      coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)
      citrate lyase, which metabolizes citrate, has been shown to be essential for
      inflammation, but the ability of exogenous citrate to impact inflammatory
      signalling cascades remains largely unknown. We hypothesized that citrate would
      modulate inflammatory responses as both a cellular metabolite and calcium
      chelator, and tested this hypothesis by determining how clinically relevant
      levels of citrate modulate monocyte proinflammatory responses to
      lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1).
      In normal medium (0.4 mM calcium), citrate inhibited LPS-induced tumour necrosis
      factor (TNF)-alpha and interleukin (IL)-8 transcripts, whereas in medium
      supplemented with calcium (1.4 mM), TNF-alpha and IL-8 levels increased and
      appeared independent of calcium chelation. Using an IL-8-luciferase plasmid
      construct, the same increased response was observed in the activation of the IL-8
      promoter region, suggesting transcriptional regulation. Tricarballylic acid, an
      inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF
      alpha, linking citrate's augmentation effect with its metabolism by ATP-citrate
      lyase. In the presence of citrate, increased histone acetylation was observed in
      the TNF-alpha and IL-8 promoter regions of THP-1 cells. We observed that citrate
      can both augment and inhibit proinflammatory cytokine production via modulation
      of inflammatory gene transactivation. These findings suggest that citrate anti
      coagulation may alter immune function through complex interactions with the
      inflammatory response.

PMID- 25619262
TI  - NADPH oxidase p22phox C242T polymorphism and ischemic cerebrovascular disease: an
      updated meta-analysis.
AB  - BACKGROUND: A growing number of studies on the associations between nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and
      risk of ischemic cerebrovascular disease have recently been published, but the
      results remain inconsistent. MATERIAL/METHODS: We performed an updated meta
      analysis to evaluate this association. Eight case-control studies were included,
      involving 2045 cases and 2102 controls. Heterogeneity was assessed by the Q test
      and the I2 statistic. Begg and Egger's tests were conducted to evaluate
      publication bias. Odds ratio (OR) was tested to identify the associations.
      RESULTS: Significant associations between p22phox gene C242T polymorphism and
      ischemic cerebrovascular disease (ICVD) risk were observed in the allelic genetic
      model (OR=1.33, 95% confidence interval [CI] 1.00-1.77, p=0.048). No statistical
      significant association was found in the dominant model (OR=0.74, 95% CI 0.54
      1.02, p=0.064) and recessive model (OR=1.40, 95% CI 0.89-2.19, p=0.146). Subgroup
      analysis showed an association in European populations for recessive model
      (OR=2.13, 95% CI 1.06-4.26, p=0.034) and no significant evidence of association
      in Asian populations was found (dominant model: OR=0.64, 95% CI 0.41-1.00,
      p=0.05; recessive model: OR=0.98, 95% CI 0.53-1.81, p=0.948; allelic model:
      OR=1.51, 95% CI 0.98-2.32, p=0.061). CONCLUSIONS: p22phox gene C242T polymorphism
      was associated with ICVD risk in the allelic genetic model, as well as in
      European populations for recessive model. No evidence showed association between
      p22phox gene C242T polymorphism and ICVD risk in the dominant model and recessive
      model. Furthermore, no association existed in Asian populations for any of the 3
      genetic models and European populations in the dominant model and allelic model.

PMID- 25619263
TI  - The SALOME study: recruitment experiences in a clinical trial offering injectable
      diacetylmorphine and hydromorphone for opioid dependency.
AB  - BACKGROUND: The Study to Assess Long-term Opioid Medication Effectiveness
      (SALOME) is a two-stage phase III, single site (Vancouver, Canada), randomized,
      double blind controlled trial designed to test if hydromorphone is as effective
      as diacetylmorphine for the treatment of long-term illicit opioid injection.
      Recruiting participants for clinical trials continues to be a challenge in
      medical and addiction research, with many studies not being able to reach the
      planned sample size in a timely manner. The aim of this study is to describe the
      recruitment strategies in SALOME, which offered appealing treatments but had
      limited clinic capacity and no guaranteed post-trial continuation of the
      treatments. METHODS: SALOME included chronic opioid-dependent, current illicit
      injection opioid users who had at least one previous episode of opioid
      maintenance treatment. Regulatory approvals were received in June 2011 and
      recruitment strategies were implemented over the next 5 months. Recruitment
      strategies included ongoing open communication with the community, a consistent
      and accessible team and participant-centered screening. All applicants completed
      a pre-screening checklist to assess prerequisites. Applicants meeting these
      prerequisites were later contacted to commence the screening process. RESULTS: A
      total of 598 applications were received over the two-year recruitment period; 130
      were received on the first day of recruitment. Of these applicants, 485 met
      prerequisites; however, many could not be found or were not reached before
      recruitment ended. For the 253 candidates who initiated the screening process,
      the average time lapse between application and screening date was 8.3 months
      (standard deviation [SD] = 4.44) and for the 202 randomized to the study, the
      average processing time from initial screen to randomization was 25.9 days (SD =
      37.48; Median = 15.0). CONCLUSIONS: As in prior trials offering injectable
      diacetylmorphine within a supervised model, recruiting participants for this
      study took longer than planned. The recruitment challenges overcome in SALOME
      were due to the high number of applicants compared with the limited number that
      could be randomized and treated. Our study emphasizes the value of integrating
      these strategies into clinical addiction research to overcome study-specific
      barriers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01447212.

PMID- 25619264
TI  - Expression of NK cell and monocyte receptors in critically ill patients-
      potential biomarkers of sepsis.
AB  - Sepsis is characterized by activation of both the innate and adaptive immune
      systems as a response to infection. During sepsis, the expression of surface
      receptors expressed on immune competent cells, such as NKG2D and NKp30 on NK
      cells and TLR4 and CD14 on monocytes, is partly regulated by pro- and anti
      inflammatory mediators. In this observational study, we aimed to explore whether
      the expression of these receptors could be used as diagnostic and/or prognostic
      biomarkers in sepsis. Patients with severe sepsis or septic shock (n = 21) were
      compared with critically ill non-septic patients (n = 15). Healthy volunteers (n
      = 15) served as controls. To elucidate variations over time, all patients were
      followed for 4 days. Cell surface expression of NKG2D, NKp30, TLR4 and CD14 and
      serum levels of IL-1beta, IL-6, IFN-gamma, TNF-alpha, IL-4 and IL-10 was
      estimated by flow cytometry. We found that NK cell expression of NKG2D and
      monocyte expression of CD14 were lower in the septic patients compared with the
      non-septic patients, both at ICU admission and during the observation period (P <
      0.01 for all comparisons). Both at ICU admission, and during the observation
      period, levels of IL-6 and IL-10 were higher in the septic patients compared with
      the non-septic patients (P < 0.001 for all comparisons). CONCLUSION: As both
      NKG2D and CD14 levels appear to distinguish between septic and non-septic
      patients, both NKG2D and CD14 may be considered potential diagnostic biomarkers
      of severe sepsis and septic shock.

PMID- 25619266
TI  - Acute pulmonary embolism: risk assessment, risk stratification and treatment
      options.
AB  - INTRODUCTION: Pulmonary embolism (PE) is a potentially life-threatening
      cardiovascular emergency with a high mortality rate. Rapid diagnosis and
      treatment are important in optimising clinical outcomes in patients with PE, and
      anticoagulants are the mainstay of treatment. Traditionally, anticoagulant
      therapy involves parenteral anticoagulants, overlapping with and followed by oral
      vitamin K antagonists. Direct oral anticoagulants (DOACs), including the factor
      Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin
      inhibitor dabigatran etexilate, have been developed to address limitations
      associated with traditional anticoagulant therapy. Apixaban, dabigatran and
      rivaroxaban have recently been approved for the treatment of acute deep vein
      thrombosis (DVT) and PE and prevention of recurrent DVT or PE. Edoxaban is
      approved in the United States but not currently in the European Union for the
      treatment of DVT and PE; approval of edoxaban in Europe is anticipated in the
      near future. OBJECTIVE: To summarise the management of patients with suspected PE
      in accordance with recent guidelines, and to discuss the evidence behind the
      recent approvals of the DOACs for the treatment of PE. DISCUSSION: Diagnosis and
      treatment of PE is guided by clinical probability scoring systems and tools for
      prognostic stratification and early mortality risk evaluation. Anticoagulants
      remain the mainstay of treatment. Successful phase III trials have demonstrated
      the efficacy of the DOACs for the treatment of DVT and PE, with a potentially
      improved safety profile, leading to their recent approval in this indication, and
      giving the clinician greater choice of anticoagulant therapies in this setting.
      CONCLUSIONS: DOACs offer an alternative and potentially simplified option for
      anticoagulation therapy in patients with PE compared with traditional
      anticoagulants and are likely to assist physicians in optimising management of
      patients with PE and improve clinical outcomes.

PMID- 25619265
TI  - Optimal duration of pre-liver transplantation anti-hepatitis C virus treatment
      with direct-acting agent sofosbuvir.

PMID- 25619267
TI  - Sinus arrest as a result of rivastigmine in an elderly dementia with Lewy bodies
      patient.

PMID- 25619268
TI  - Use of tigecycline in elderly patients for Clostridium difficile infection.

PMID- 25619269
TI  - Cognitive examination in older adults living in temporary apartments after the
      Great East Japan Earthquake.

PMID- 25619270
TI  - Development of conversion formulae between 4-m, 5-m and 6-m gait speed.

PMID- 25619271
TI  - Predictors of death among nursing home patients: a 5-year prospective study.

PMID- 25619272
TI  - Degree of physical activity in elderly disaster victims during the acute phase of
      the Great East Japan Earthquake.

PMID- 25619273
TI  - Re: Growing research on sarcopenia in Asia.

PMID- 25619274
TI  - Small Group Teaching in a psychiatric hospital for dementia patients.

PMID- 25619275
TI  - Incidence of type 2 diabetes and number of events attributable to abdominal
      obesity in China: A cohort study.
AB  - BACKGROUND: The aim of the present study was to estimate the incidence of type 2
      diabetes (T2D) and the number of diabetes events attributable to abdominal
      obesity in China. METHODS: A cohort study was conducted in a sample of 24,996
      Chinese adults aged 35-74 years, with 19.9% of subjects lost to follow-up. Waist
      circumference (WC) was measured at baseline in 1998 and 2000-01, and abdominal
      obesity was defined as WC >= 90 cm in men and >=80 cm in women. Information on
      incident diabetes was collected during follow-up in 2007-08. We estimated the
      number of T2D events attributed to abdominal obesity using confounder-adjusted
      population-attributable risk, incidence of diabetes, and the population size of
      China in 2010. RESULTS: After a mean follow-up of 8.0 years, the age-standardized
      incidence of T2D was 9.6 and 9.2 per 1000 person-years in men and women,
      respectively. Abdominal obesity accounted for 28.1% (95% confidence interval [CI]
      14.8%, 40.5%) of incident diabetes among men and 41.2% (95% CI 28.3%, 52.6%)
      among women using the diagnostic criteria of abdominal obesity recommended by the
      International Diabetes Federation. We estimated that, in 2010, 2.4 (95% CI 1.5,
      3.2) million diabetes events were attributable to abdominal obesity: 1.0 (95% CI
      0.5, 1.4) million in men and 1.4 (95% CI 1.0, 1.8) million in women. CONCLUSIONS:
      Abdominal obesity is a major risk factor for T2D. Strengthening programs and
      initiatives for preventing and controlling obesity focusing on lifestyle changes
      should be a priority in the national strategy to reduce diabetes burden in China.

PMID- 25619276
TI  - Dynamical analysis of mCAT2 gene models with CTN-RNA nuclear retention.
AB  - As an experimentally well-studied nuclear-retained RNA, CTN-RNA plays a
      significant role in many aspects of mouse cationic amino acid transporter 2
      (mCAT2) gene expression, but relevant dynamical mechanisms have not been
      completely clarified. Here we first show that CTN-RNA nuclear retention can not
      only reduce pre-mCAT2 RNA noise but also mediate its coding partner noise. Then,
      by collecting experimental observations, we conjecture a heterodimer formed by
      two proteins, p54(nrb) and PSP1, named p54(nrb)-PSP1, by which CTN-RNA can
      positively regulate the expression of nuclear mCAT2 RNA. Therefore, we construct
      a sequestration model at the molecular level. By analyzing the dynamics of this
      model system, we demonstrate why most nuclear-retained CTN-RNAs stabilize at the
      periphery of paraspeckles, how CTN-RNA regulates its protein-coding partner, and
      how the mCAT2 gene can maintain a stable expression. In particular, we obtain
      results that can easily explain the experimental phenomena observed in two cases,
      namely, when cells are stressed and unstressed. Our entire analysis not only
      reveals that CTN-RNA nuclear retention may play an essential role in indirectly
      preventing diseases but also lays the foundation for further study of other
      members of the nuclear-regulatory RNA family with more complicated molecular
      mechanisms. 

PMID- 25619277
TI  - How pyridoxal 5'-phosphate differentially regulates human cytosolic and
      mitochondrial serine hydroxymethyltransferase oligomeric state.
AB  - Adaptive metabolic reprogramming gives cancer cells a proliferative advantage.
      Tumour cells extensively use glycolysis to sustain anabolism and produce serine,
      which not only refuels the one-carbon units necessary for the synthesis of
      nucleotide precursors and for DNA methylation, but also affects the cellular
      redox homeostasis. Given its central role in serine metabolism, serine
      hydroxymethyltransferase (SHMT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme,
      is an attractive target for tumour chemotherapy. In humans, the cytosolic isoform
      (SHMT1) and the mitochondrial isoform (SHMT2) have distinct cellular roles, but
      high sequence identity and comparable catalytic properties, which may complicate
      development of successful therapeutic strategies. Here, we investigated how
      binding of the cofactor PLP controls the oligomeric state of the human isoforms.
      The fact that eukaryotic SHMTs are tetrameric proteins while bacterial SHMTs
      function as dimers may suggest that the quaternary assembly in eukaryotes
      provides an advantage to fine-tune SHMT function and differentially regulate
      intertwined metabolic fluxes, and may provide a tool to address the specificity
      problem. We determined the crystal structure of SHMT2, and compared it to the apo
      enzyme structure, showing that PLP binding triggers a disorder-to-order
      transition accompanied by a large rigid-body movement of the two cofactor-binding
      domains. Moreover, we demonstrated that SHMT1 exists in solution as a tetramer,
      both in the absence and presence of PLP, while SHMT2 undergoes a dimer-to
      tetramer transition upon PLP binding. These findings indicate an unexpected
      structural difference between the two human SHMT isoforms, which opens new
      perspectives for understanding their differing behaviours, roles or regulation
      mechanisms in response to PLP availability in vivo. 

PMID- 25619278
TI  - Absorption and intermediary metabolism of purines and pyrimidines in lactating
      dairy cows.
AB  - About 20 % of ruminal microbial N in dairy cows derives from purines and
      pyrimidines; however, their intermediary metabolism and contribution to the
      overall N metabolism has sparsely been described. In the present study, the
      postprandial patterns of net portal-drained viscera (PDV) and hepatic metabolism
      were assessed to evaluate purine and pyrimidine N in dairy cows. Blood was
      sampled simultaneously from four veins with eight hourly samples from four multi
      catheterised Holstein cows. Quantification of twenty purines and pyrimidines was
      performed with HPLC-MS/MS, and net fluxes were estimated across the PDV, hepatic
      tissue and total splanchnic tissue (TSP). Concentration differences between veins
      of fifteen purine and pyrimidine nucleosides (NS), bases (BS) and degradation
      products (DP) were different from zero (P<= 0.05), resulting in the net PDV
      releases of purine NS (0.33-1.3 mmol/h), purine BS (0.0023-0.018 mmol/h), purine
      DP (7.0-7.8 mmol/h), pyrimidine NS (0.30-2.8 mmol/h) and pyrimidine DP (0.047
      0.77 mmol/h). The hepatic removal of purine and pyrimidine was almost equivalent
      to the net PDV release, resulting in no net TSP release. One exception was uric
      acid (7.9 mmol/h) from which a large net TSP release originated from the
      degradation of purine NS and BS. A small net TSP release of the pyrimidine DP
      beta-alanine and beta-aminoisobutyric acid (-0.032 to 0.37 mmol/h) demonstrated
      an outlet of N into the circulating N pool. No effect of time relative to feeding
      was observed (P>0.05). These data indicate that considerable amounts of N are
      lost in the dairy cow due to prominent intermediary degradation of purines, but
      that pyrimidine N is reusable to a larger extent.

PMID- 25619280
TI  - Influence of source and drain contacts on the properties of indium-gallium-zinc
      oxide thin-film transistors based on amorphous carbon nanofilm as barrier layer.
AB  - Amorphous indium-gallium-zinc-oxide thin film transistors (alpha-IGZO TFTs) with
      damage-free back channel wet-etch (BCE) process were achieved by introducing a
      carbon nanofilm as a barrier layer. We investigate the effects of different
      source-and-drain (S/D) materials on TFT performance. We find the TFT with Ti/C
      S/D electrodes exhibits a superior performance with higher output current, lower
      threshold voltage, and higher effective electron mobility compared to that of
      Mo/C S/D electrodes. Transmittance electron microscopy (TEM) and X-ray
      photoelectron spectroscopy (XPS) are employed to analysis the interfacial
      interaction between S/D metal/C/alpha-IGZO layers. The results indicate that the
      better performance of TFTs with Ti/C electrodes should be attributed to the
      formations of Ti-C and Ti-O at the Ti/C-contact regions, which lead to a lower
      contact resistance, whereas Mo film is relatively stable and does not react
      easily with C nanofilm, resulting in a nonohmic contact behavior between Mo/C and
      alpha-IGZO layer. However, both kinds of alpha-IGZO TFTs show good stability
      under thermal bias stress, indicating that the inserted C nanofilms could avoid
      the impact on the alpha-IGZO channel regions during S/D electrodes formation.
      Finally, we successfully fabricated a high-definition active-matrix organic
      lighting emitting diode prototype driven by alpha-IGZO TFTs with Ti/C electrodes
      in a pilot line. 

PMID- 25619281
TI  - Successful delivery in a patient with clinically amyopathic dermatomyositis
      during pregnancy despite first-trimester acute exacerbation of interstitial lung
      disease.
AB  - A 37-year-old woman with rheumatoid arthritis and interstitial lung disease (ILD)
      developed clinically amyopathic dermatomyositis (CADM) after achieving pregnancy
      through in vitro fertilization. She was given oral prednisolone, which improved
      her respiratory status, and delivered a healthy baby at 35 weeks' gestation.
      There are few reports of successful outcomes for CADM during pregnancy; to the
      best of our knowledge, this is the first report of successful delivery in a
      patient with both CADM and ILD.

PMID- 25619283
TI  - Chronological changes in baseline disease activity of patients with rheumatoid
      arthritis who received biologic DMARDs between 2003 and 2012.
AB  - BACKGROUND/PURPOSE: The use of biologic disease-modifying anti-rheumatic drugs
      (DMARDs) for rheumatoid arthritis (RA) has been increasing since 2003. In this
      study, we evaluated changes in the characteristics of patients receiving biologic
      DMARDs daily, in Japan. METHODS: The characteristics of all RA patients who
      received any biologic DMARD at the Institute of Rheumatology, Tokyo Women's
      Medical University, within 1 year after its approval in Japan, were
      retrospectively evaluated. The periods of patient enrollment for each biologic
      agent were: infliximab (IFX), 2003-2004; etanercept (ETN), 2005-2006; tocilizumab
      (TCZ), 2008-2009; adalimumab (ADA), 2008-2009; abatacept (ABT), 2010-2011; and
      golimumab (GLM), 2011-2012. We retrospectively collected individual patient
      characteristics, concomitant medication usage, and disease activity assessed by
      disease activity score 28 (DAS28) at the time of administration, from the medical
      records. The retention rate for each agent at 6 months after treatment initiation
      was also assessed. RESULTS: The numbers of patients who received each biologic
      DMARD at our institute within 1 year after its approval were: IFX, 49; ETN, 50;
      TCZ, 62; ADA, 52; ABT, 40; and GLM, 77. From 2003 to 2012, the proportion of
      patients with prior use of any biologic DMARD increased, as did concomitant use
      and dose of methotrexate (MTX); however, corticosteroid use and doses decreased.
      DAS28, at the time of treatment initiation, gradually decreased. At the time of
      IFX administration, 75% and 25% of patients had high and moderate disease
      activity respectively, compared to 25% and 58% respectively, of patients who
      received GLM. No significant difference was observed in the retention rate of
      biologic DMARDs at 6 months (range, 75.0% to 89.6%). CONCLUSION: Baseline disease
      activity of RA patients who received biologic DMARDs between 2003 and 2012 has
      changed from high to moderate in daily practice in Japan.

PMID- 25619282
TI  - Successful treatment with humanized anti-interleukin-6 receptor antibody
      (tocilizumab) in a case of AA amyloidosis complicated by familial Mediterranean
      fever.
AB  - Familial Mediterranean fever (FMF) is a well-known cause of secondary AA
      amyloidosis. Colchicine is generally considered to be the most effective
      treatment for FMF and FMF-associated amyloidosis, but the management of patients
      who are refractory to colchicine remains controversial. We encountered a 51-year
      old Japanese man with suspected FMF, who had periodic fever with abdominal pain,
      polyarthritis, and nephropathy (serum creatinine of 1.9 mg/dL and 24-h protein
      excretion of 3.8 g). FMF was diagnosed by mutation analysis of the Mediterranean
      fever (MEFV) gene, which revealed that the patient was compound heterozygous for
      the marenostrin/pyrin variant E148Q/M694I. AA amyloidosis was diagnosed by renal
      and gastric biopsy. Colchicine was administered, but his arthritis persisted, and
      serum creatinine increased to 2.4 mg/dL. Therefore, a humanized anti-interleukin
      6 receptor antibody (tocilizumab) was administered at a dose of 8 mg/kg on a
      monthly basis. Both arthritis and abdominal pain subsided rapidly, and C-reactive
      protein (CRP) decreased from 2.5 to 0.0 mg/dL. After 2 years, his serum
      creatinine was decreased to 1.5 mg/dL and proteinuria was improved to 0.3 g
      daily. In addition, repeat gastric biopsy showed a marked decrease of AA
      amyloidosis. This case suggests that tocilizumab could be a new therapeutic
      option for patients with FMF-associated AA amyloidosis if colchicine is not
      effective. 

PMID- 25619284
TI  - Nodules in patients with rheumatoid arthritis and methotrexate treatment.

PMID- 25619285
TI  - Impact of the imaginary part of the surface dilatational modulus on the splashing
      behavior of drops.
AB  - The relation between the complex surface dilatational modulus E of aqueous
      surfactant solutions and the splashing behavior of their drops on liquid surfaces
      was investigated. The surface dilatational modulus E of selected surfactant
      systems has been determined in the frequency range of 3 to 500 Hz by means of the
      oscillating bubble technique. According to the functional dependence of the phase
      phi of the complex modulus E(omega, c)exp[iphi(omega, c)] at higher frequencies,
      adsorption layers can be classified as surface elastic or surface viscoelastic.
      Each behavior shows pronounced differences in drop splashing experiments. The
      impact of a drop on the liquid was monitored with a high-speed camera. The splash
      of a drop is a rather complex phenomenon, so the focus of this article is to
      establish a relationship between the imaginary part of the surface dilatational
      modulus E and the height of the drop rebound. These findings may be of importance
      for formulations in crop protection, introducing a chemical way to influence the
      impact of drops on solid and liquid interfaces. 

PMID- 25619286
TI  - [Bottleneck effects of cleft lip and palate research].

PMID- 25619287
TI  - [Discussion of the surgical treatment influence on the growth and development of
      maxillofacial bone in patients with cleft lip and palate].

PMID- 25619288
TI  - [How to enhance the impact of charity program for clefts quickly].

PMID- 25619289
TI  - [Duration of speech therapy in patients with or without velopharyngeal
      insufficency after palatoplasty].
AB  - OBJECTIVE: To investigate the duration of speech therapy of patients with or
      without velopharyngeal insufficency after palatoplasty. METHODS: One hundred and
      one cleft-palate patients with velopharyngeal incompetence (VPI) and eighty-seven
      without VPI were selected in the study. The treatment times of the patients who
      completed the speech therapy were counted and analyzed. RESULTS: The mean
      treatment frequency in VPI group was 17 times, and in the group without VPI this
      number was 13 (P < 0.05). In 39 VPI patients with signs of velocardiofaical
      syndrome, the mean treatment frequency was 19 times, and the mean treatment
      frequency of the other 62 patents with nonsyndromic VPI was 15 times (P < 0.05).
      CONCLUSIONS: The duration of speech therapy in VPI patients is longger than that
      in patients without VPI after palatoplasy, but individualized treatment is
      necessary.

PMID- 25619290
TI  - [Tetrachlorodibenzo-p-dioxin-induced cleft palate because of partial loss of cell
      polarity to interfere with apoptosis during early developmental stage].
AB  - OBJECTIVE: In this study, folic acid (FA) was tested for antiteratogenic effects
      on Tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate in fetal mice.
      METHODS: In the present study, pregnant mice were dosed with TCDD 24 ug/kg and
      with or without FA 5 mg/kg body weight on gestation day 10. Control group mice
      received sesame oil 50 ml/kg body weight on gestation day(GD)10. The mice were
      sacrificed on GD12.5, GD13.5, GD14.5, GD15.5 and GD16.5. From each pregnant mouse
      on GD16.5, embryos were obtained to examine under a dissecting microscope, and
      routine histology was performed for detection and classification of palatal
      clefts. The fetuses were prepared for histologic examination, scanning electron
      microscope and TdT-mediated X-dUTP nick and labeling (TUNEL). On GD12.5, GD13.5,
      GD14.5 and GD15.5. Meanwhile, real-time (RT)-PCR was employed to detect the mRNA
      expression levels about arylhydrocarbon receptor (AHR) and transforming growth
      factor (TGF)beta3 in this animal model. RESULTS: Total frequencies of clefts were
      70.2% in TCDD group(group B) and 66.3% in TCDD+FA group(group C) in relation to
      control fetuses(group A). Filopodia disappeared completely at the medial edge
      epithelia surface on GD15.5 (group A), GD12.5 (group B) and GD14.5 (group C). the
      RT-PCR results showed that TGF -beta3 expression was down-regulated on GD13.5 and
      GD14.5 compared to the control. CONCLUSIONS: It is found that folic acid has no
      protects agaist 2.3.7.8-TCDD-indued cleft palate in the experiment. Meanwhile,
      TCDD repressed the TGF-beta3 expression during the palatal development. Anormal
      apoptosis was induced by 2, 3, 7, 8-TCDD at the medial edge epithelia (MEE)
      during the early development stage.

PMID- 25619291
TI  - [Inconformity between soft tissue defect and bony defect in incomplete cleft
      palate].
AB  - OBJECTIVE: To evaluate the inconformity between soft tissue defect and bony
      defect by observing the cleft extent of palate with complete secondary palate
      bony cleft in incomplete cleft palate patient. METHODS: The patients with
      incomplete cleft palate treated in Hospital of Stomatology Peking University from
      July 2012 to June 2013 were reviewed, of which 75 cases with complete secondary
      palate bony cleft were selected in this study. The CT scan and intraoral
      photograph were taken before operation. The patients were classified as four
      types according to the extent of soft tissue defect. Type 1: soft tissue defect
      reached incisive foremen region, Type 2 was hard and soft cleft palate, Type 3
      soft cleft palate and Type 4 submucous cleft palate. Type 1 was defined as
      conformity group (CG). The other three types were defined as inconformity group
      (ICG) and divided into three subgroups (ICG-I), (ICG-II) and (ICG-III). RESULTS:
      Fifty-seven patients were in ICG group, and the rate of inconformity was 76%
      (57/75). The percentage of ICG-I, ICG-II and ICG-III was 47% (27/57), 23% (13/57)
      and 30% (17/57), respevtively. CONCLUSIONS: There are different types of soft
      tissue deformity with complete secondary palate bony cleft. The inconformity
      between soft tissue and hard tissue defect exits in 3/4 of isolated cleft palate
      patients.

PMID- 25619292
TI  - [7-Dehydrocholesterol reductase regulated the palatal development by the sonic
      hedgehog-bone morphogenetic protein 2 signal pathway].
AB  - OBJECTIVE: To investigate the effect of 7- dehydrocholesterol reductas (Dhcr-7)
      gene silencing on the palatal development by sonic hedgehog (Shh)-bone
      morphogenetic protein2(BMP-2) signal pathway in vitro. METHODS: A total of 60
      pairs of palatal shelves fromgestation day (GD) 13.5 mouse embryos were divided
      into three groups (A, B, C) of 20 randomly. In group A (control), palatal shelves
      were cultured with medium containing no cholesterol.In group B (Dhcr-7-siRNA),
      palatal shelves were cultured without cholesterol medium but containing Dhcr-7
      siRNA adenovirus. After 48h, the culture medium of groups A and B were changed
      with medium without cholesterol. In group C (cholesterol), palatal shelves were
      cultured without cholesterol medium but containing Dhcr-7 siRNA adenovirus. After
      48h, the culture medium of group C was changed with medium containing 600 mg/L
      cholesterol. After 72h again, tissues dyeing and scanning electron microscope
      (SEM) technique were used to observe morphological changes of palates. Both RT
      PCR and Western blottingtechniques were used to measure mRNA and protein
      expressions for Dhcr-7, Shh, and BMP-2, respectively. RESULTS: The tissues dyeing
      and SEM showedthat the palates fusedin groups A and Candthe palates did not fuse
      in group B eventually. The expression of both mRNA and proteins for Shh and BMP-2
      in group B wasdecreased with the Dhcr-7 reduction. In group B, the mRNA and
      protein expression of Shh was separately 0.063+/-0.018 and 0.092+/-0.065;the mRNA
      and protein expression quantity of BMP- 2 was separately 0.054+/-0.018 and
      0.049+/-0.021. In group A, the mRNA and protein expression of Shh was separately
      0.667+/-0.093 and 0.639+/-0.078;the mRNA and protein expression of BMP-2 was
      separately 0.591 +/- 0.043 and 0.569 +/- 0.081. The difference of Shh and BMP- 2
      mRNA and protein expression between A and B group were statistically significant
      separately (P < 0.05). The expression of both mRNA and protein for Dhcr-7
      (0.074+/-0.034 and 0.075+/-0.028) did not changebasicallyin group C, compared
      with the Dhcr- 7expression of mRNA and protein (0.083+/-0.045; 0.067+/-0.065) in
      group B, the difference wasnot statistically significant(P > 0.05). In group C,
      the mRNA and protein expressionof Shh (0.649+/-0.085 and 0.608+/-0.092) and BMP-2
      (0.578+/-0.062 and 0.548+/-0.065) were significantly increased. The difference of
      Shh and BMP-2 mRNA and protein expression between B and C group were
      statistically significant separately (P < 0.05). CONCLUSIONS: Dhcr-7 could
      influence the expression of Shh and BMP-2. Dhcr-7 reductase regulated the palatal
      development by the Shh-BMP-2 signal pathway.

PMID- 25619293
TI  - [Association between gingival crevicular fluid leptin level and periodontal
      parameters in patients with aggressive periodontitis].
AB  - OBJECTIVE: To determine the level of leptin in gingival crevicular fluid (GCF) of
      patients with aggressive periodontitis (AgP) and to analyze the relationship
      between leptin and periodontal cilinical parameters. METHODS: Fifty-four patients
      with AgP and 30 healthy controls were recruited. Detailed clinical examinations
      were conducted, and clinical parameters such as bleeding index (BI), probing
      depth (PD), attachment loss (AL) were recorded. Two teeth were selected as test
      teeth in each subject, one from posterior area and the other from anterior
      region. The level of GCF leptin was measured by enzyme linked immunosorbent
      assay. RESULTS: The level of GCF leptin in AgP patients was significantly lower
      than that of control subjects [(16.5+/-4.6) ng vs.(26.0+/-6.0) ng, P < 0.05]. The
      level of GCF leptin was negatively related to BI (-0.306, P < 0.01), PD (-0.346,
      P < 0.01) and AL (-0.250, P < 0.01). CONCLUSIONS: AgP patients have significantly
      decreased level of GCF leptin and the level of leptin was negatively related to
      BI, PD and AL.

PMID- 25619294
TI  - [Effect of high glucose on the secretion of cytokines induced by Porphyromonas
      gingivalis lipopolysaccharide].
AB  - OBJECTIVE: To investigate the influence of high glucose on
      Porphyromonasgingivalis (Pg) lipopolysaccharide (LPS) stimulating human gingival
      fibroblasts (HGF) to secret the cytokines. METHODS: HGF were obtained from the
      primary culture of the tissue explants. Cells were divided into four groups, low
      glucose (5.5 mmol/L) + 1 mg/L Pg LPS (group A);low glucose + 10 mg/L Pg LPS
      (group B); high glucose (25 mmol/L) +1 mg/L Pg LPS(group C); high glucose+10 mg/L
      Pg LPS (group D). The levels of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) in cell supernatants were detected by enzyme- linked
      immunosorbent assay at 6 h and 12 h. The expressions of toll-like receptor 2, 4
      (TLR-2, 4) were examined by real-time polymerase chain reaction. After
      pretreatment with anti-TLR2 and anti-TLR4 monoclonal antibody in HGF, TNF-alpha
      and L-1beta levels were detected. RESULTS: TNF-alpha concentration increased
      obviously in high glucose 6 h and 12 h after Pg LPS stimulation (P < 0.01). IL
      1beta secretion increased (P < 0.01). Meanwhile, TLR2, 4 mRNA expression
      increased, especially in high glucose+10 mg/L Pg LPS (P < 0.01). After inhibition
      of the TLR2, 4 in high glucose + 10 mg/L Pg LPS respectively, TNF-alpha level
      [(297.16+/-11.49), (390.01+/-12.81) ng/L] decreased (F = 166.02, P < 0.01), and
      IL-1beta level [(49.90+/-4.08), (99.35+/-5.01) ng/L] also decreased (F = 153.51,
      P < 0.01). CONCLUSIONS: High glucose may promote Pg LPS to stimulate the
      secretion of TNF-alpha and IL-1beta through regulating TLR2, 4 expression, which
      suggests that the elevating blood glucose precipitate in aggravating the process
      of periodontal disease.

PMID- 25619295
TI  - [Analysis of microbial diversity of supra-gingival plaque in dental caries].
AB  - OBJECTIVE: To investigate the microbial composition and differences in dental
      plaque of caries and caries-free adults. METHODS: Caries-active (n = 16) was
      defined as an individual who had at least three untreated decayed tooth and
      decayed-missing-filled-tooth (DMFT) score greater than 6. Caries-free (n = 16)
      was defined as an individual who had a DMFT score equal to zero. The patients
      were 18-35 years old. Samples from supra-gingival plaque were obtained and PCR
      denaturing gel electrophoresis cloning and sequencing of caries pathogens were
      used to catch the core microbial of dental caries. RESULTS: Six phylum, 28 genus
      and 88 species were detected. In caries group, Prevotella, Capnocytophaga,
      Actinomyces, Veillonella and Corynebacterium were predominant, accounting for
      56.2% (334/594) of the total cloning number of caries group. Caries-free group
      contained more predonminant genus than caries group. Prevotella, Veillonella,
      Capnocytophaga, Corynebacterium, Streptococcus, Actinomyces, Aggregatibacter and
      Neisseria were predominant, accounting for 65.2% (354/543) of the total cloning
      number of caries-free group. Caries group had less diversity than the caries-free
      group. The difference was statistically significant (P < 0.05). CONCLUSIONS:
      Caries might be caused by potentially pathogenic microbial communities rather
      than a single pathogen. In the progress of dental caries, the microbial diversity
      decreased.

PMID- 25619296
TI  - [Changes of protein kinases Mzeta expression in the anterior cingulate cortex
      after applying three different magnitude of orthodontic force].
AB  - OBJECTIVE: To investigate the regulatory effect of central synaptic plasticity on
      pain induced by experimental tooth movement and to analyzethe expression of
      protein kinases Mzeta (PKMzeta) in the anterior cingulate cortex (ACC) after
      applying different magnitude of orthodontic force. METHODS: One hundred and
      thirty-six male Sprague-Dawley (SD) rats (200-250 g) were used in this study.
      Orthodontic tooth movement devices were placed on the teeth in the experimental
      group, and different orthodontic forces (0.39, 0.78, 1.17 N) were applied to move
      the maxillary first molars, respectively. The same mechanical devices were placed
      on the teeth in sham-treated group and no orthodontic force was applied. No
      orthodontic procedure was applied in blank control group. The average time spent
      on mouth- wiping behavior in each group was recorded after experimental tooth
      movement. Brain tissue of the anterior cingulate cortex was isolated on day 3
      after experiment, and the expression level of PKMzeta was analyzed with the
      method of immunohistochemistry and enzyme-linked immune sorbent assay. zeta
      pseudosubstrate inhibitory peptide (ZIP), a selective inhibitor for PKMzeta, was
      injected into ACC on day 3 after experimental tooth movement, and the effects of
      ZIP on mouth-wiping behavior were evaluated. RESULTS: No statistical difference
      was found between the blank control group and the sham- treated group in the
      average time spent on mouth-wiping, value of A and expression level of PKMzeta (P
      > 0.05). Compared with the sham-treated group and blank control group, the
      average time of mouth-wiping behavior [(58.6+/-6.9), (66.3+/-7.8), (78.9+/-8.7)
      s], value of A (4 569+/-454, 6 850+/-365, 8 294+/-558) and expression level of
      PKMzeta [(0.32+/-0.02), (0.34+/-0.02), (0.36+/-0.02) mg/L] in 0.39, 0.78, 1.17 N
      force group were found to be up-regulated with the increase of orthodontic force
      (P < 0.05). LSD test in three experimental sub-group showed statistical
      difference (P < 0.05). After microinjection of ZIP, the average time spent on
      mouth-wiping behavior significantly decreased (P < 0.01), while microinjecting
      saline did not change rats' mouth-wiping behavior (P > 0.05). CONCLUSIONS: More
      pain caused by increased orthodontic force maybe due to the up-regulation of
      PKMzeta in the anterior cingulate cortex.

PMID- 25619297
TI  - [Effect of dentin proteoglycans on the bonding properties of dentin].
AB  - OBJECTIVE: To investigate the potential effect of proteoglycan (PG) and
      glycosaminoglycan (GAG) on the bonding of etch and rinse adhesive to dentin, in
      order to improve the bonding effect of dentin. METHODS: Forty-two extracted
      molars were used to obtain standard dentin bonding surface, and the specimens
      were etched for 15 s with 37% phosphoric acid and divided into three groups using
      a table of random numbers. Then the three groups undergone different incubating
      procedures as follow: specimens in chondroitinase ABC (C-ABC) group were
      incubated with C-ABC at 37  degrees C for 48 h in vibrator. Specimens in trypsin
      (TRY) group were incubated with trypsin, and specimens in the control group were
      incubated with deionized water for 48 h in the oscillators. Then specimens in
      each group were randomly assigned into two subgroups, A (Adper(TM) Single Bond 2)
      and B (Prime & Bond NT) (n = 7). The microtensile bond strength (uTBS), fracture
      mode and bonding interface morphology of the specimens were evaluated via
      microtensile testing, stereo microscope and field emission scanning electron
      microscopy (FE-SEM) respectively after specimens being incubated in 37  degrees C
      water for 24 h. RESULTS: The immediate uTBS of C-ABC group bonding with adhesive
      A and B [(32.9+/-2.5) and (26.8+/-2.2) MPa] were significantly lower than that of
      the control group [(40.7+/-3.3) and (34.6+/-3.7) MPa] (P < 0.05). While the
      immediate uTBS of TRY group [(49.0 +/- 3.6) and (44.5 +/- 3.0) MPa] were
      significantly higher than that of the control group(P < 0.05). CONCLUSIONS:
      Dentin PG participates in the dentin bonding process. Removal of PG increased the
      immediate uTBS of dentin and total etching adhesives, while removal of GAG
      decreased the immediate uTBS.

PMID- 25619298
TI  - [Study on construction and biological effects of lipopolysaccharide-amine
      nanopolymersomes/hyaluronic acid polyelectrolyte multilayer films on titanium
      surface].
AB  - OBJECTIVE: To provide a basis for surface modification of polyelectrolyte
      multilayer films (PEM) on implants by exploring the effects of immobilization of
      PEM on titanium surfaces on their cell biological effects. METHODS: By using
      plasmid of bone morphogenetic protein-2 (pBMP-2)-loaded lipopolysaccharide-amine
      nanopolymersomes (pLNP) as cationic polyelectrolytes and hyaluronic acid (HA) as
      anionic polyelectrolytes. PEM were constructed on alkaline-heat treated titanium
      surfaces via layer by layer self-assembly(LbL) technique. A successive deposition
      of HA and pLNP on titanium surfaces was defined as one cycle of assembly. The
      morphology of titanium surface before and after assembly treatment was observed
      by scanning electron microscopy (SEM). The ultraviolet (UV) spectra and surface
      contact angles of PEM with different self-assembly cycles were measured. The
      adhesion and proliferation of mesenchymal stem cell (BMSC) on surfaces of group A
      (4 cycles of assembly, with outermost layer of pLNP), group B (4.5 cycles of
      assembly, with outermost layer of HA), blank control (polished titanium, Ti
      group) and alkaline-heat treated titanium (Ti-OH group) were investigated. Cell
      differentiation indexed by alkaline phosphatase activity (ALP) and in situ
      transfection of BMSC on surfaces of group A, Ti, negative control [4 cycles of
      assembly without pBMP- 2] were evaluated. RESULTS: Self assembly of PEM made the
      titanium surface become relatively smooth. DNA absorption peaked appear at 260 nm
      in UV spectra, and the absorption intensity increased with assembly, suggesting
      the successful construction of PEM. After alkali- heat treatment, the surface
      contact angle of titanium decreased from (62.6+/-4.9)  degrees  to (8.1+/-2.2) 
      degrees . During LbL, with alternately introducing pLNP and HA, the contact angle
      increased in a jagged mode at a gradually decreased rate, which further proved
      the success of assembly. Cell adhesion for group A at 0.5 and 1 h was 0.415+/
      0.085 and 0.426+/-0.048, which was significantly higher than those for group B
      (0.299+/-0.012, 0.355+/-0.022), Ti-OH group (0.225+/-0.007, 0.260+/-0.010) and Ti
      group (0.302+/-0.056, 0.339+/-0.028) (P < 0.01). Cell proliferation for group A
      and B at 3, 5 and 7 d were significantly higher than those for Ti and Ti-OH group
      (P < 0.01). ALP in group A at day 7 was 261+/-58, which was significantly higher
      than those in group B and Ti group. Group A had in situ transfection capability
      for BMSC. CONCLUSIONS: PEM with good cell biological effects can be constructed
      successfully on titanium surfaces using gene- loaded lipopolysaccharide- amine
      nanopolymersomes and hyaluronic acid.

PMID- 25619299
TI  - [Debate on several hot issues of occlusion].

PMID- 25619300
TI  - [Emergency of common critical events in dental clinic].

PMID- 25619301
TI  - [Research progress in FadA from Fusobacterium nucleatum].

PMID- 25619302
TI  - [Allergy caused by the cobalt element inside a cobalt-chromium alloy porcelain
      full crown: a case report].

PMID- 25619303
TI  - UV Sunscreens of Microbial Origin: Mycosporines and Mycosporine- like Aminoacids.
AB  - Exposure to ultraviolet radiation (UVR) is harmful to living organisms, causing
      damage to macromolecules such as DNA, RNA, proteins and lipids. Depending on the
      wavelength, the injury could be direct or indirect through reactive oxygen
      intermediates, so it is desirable to find compounds that can reduce both. Many
      organic chemicals used in commercial sunscreen possess estrogenic activity in
      vivo. In this report we analyzed recent patents related to UV sunscreens of
      microbial origin, in particular mycosporines (MYC) and mycosporine-like
      aminoacids (MAA). Both are promising natural alternatives for both direct (UV
      absorption) and indirect (antioxidant) protection, given they show strong
      photostability and absence of cytotoxicity. It becomes clear that although the
      search for natural photoprotective molecules is relatively recent, efforts have
      been invested mainly in marine environments, remaining still many potential
      photoprotective molecules to find in other type of habitats. Furthermore,
      unicellular microorganisms have several advantages for the production of
      metabolites of interest, since they improve the production costs due to its
      simplicity of culture and easy genetic manipulation. The knowledge of the
      biosynthesis pathway of MYC and MAA is essential to improve rationally their
      expression levels. Currently, only the MAA pathway in bacteria has been reported,
      remaining the MYC pathway unclear. Future perspectives include the heterologous
      expression of MYC and/or MAA in industrially friendly microorganisms (bacteria
      and yeast) in order to co-produce different UV-protective molecules and thus
      cover a broader UV spectrum and simplify the production process. 

PMID- 25619304
TI  - Molecular dynamics of spider dragline silk fiber investigated by 2H MAS NMR.
AB  - The molecular dynamics of the proteins that comprise spider dragline silk were
      investigated with solid-state (2)H magic angle spinning (MAS) NMR line shape and
      spin-lattice relaxation time (T1) analysis. The experiments were performed on
      (2)H/(13)C/(15)N-enriched N. clavipes dragline silk fibers. The silk protein side
      chain and backbone dynamics were probed for Ala-rich regions (beta-sheet and 31
      helical domains) in both native (dry) and supercontracted (wet) spider silk. In
      native (dry) silk fibers, the side chains in all Ala containing regions undergo
      similar fast methyl rotations (>10(9) s(-1)), while the backbone remains
      essentially static (<10(2) s(-1)). When the silk is wet and supercontracted, the
      presence of water initiates fast side-chain and backbone motions for a fraction
      of the beta-sheet region and 31-helicies. beta-Sheet subregion 1 ascribed to the
      poly(Ala) core exhibits slower dynamics, while beta-sheet subregion 2 present in
      the interfacial, primarily poly(Gly-Ala) region that links the beta-sheets to
      disordered 31-helical motifs, exhibits faster motions when the silk is
      supercontracted. Particularly notable is the observation of microsecond backbone
      motions for beta-sheet subregion 2 and 31-helicies. It is proposed that these
      microsecond backbone motions lead to hydrogen-bond disruption in beta-sheet
      subregion 2 and helps to explain the decrease in silk stiffness when the silk is
      wet and supercontracted. In addition, water mobilizes and softens 31-helical
      motifs, contributing to the increased extensibility observed when the silk is in
      a supercontracted state. The present study provides critical insight into the
      supercontraction mechanism and corresponding changes in mechanical properties
      observed for spider dragline silks. 

PMID- 25619305
TI  - Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV
      replication in chronic hepatitis.
AB  - Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the
      3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability
      and HLA-G protein level variation. We evaluated the association between the HLA-G
      14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV)
      infection in a case-control study. Genomic DNA was extracted from 263 patients
      with chronic HBV hepatitis and 246 control subjects and was examined for the HLA
      G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in
      chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis
      stages and in a control population. There was no statistical significant
      association between the 14-bp Ins/Del polymorphism and increased susceptibility
      to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The
      stratification of HBV patients based on HBV DNA levels revealed an association
      between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV
      DNA levels. In particular, the Ins allele was significantly associated with high
      HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was
      associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility
      to high HBV replication compared with the Del/Del and Ins/Del genotypes. This
      susceptibility is linked to the presence of two Ins alleles. No association was
      observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV
      infection. We observed an association between the 14-bp Ins/Del polymorphism and
      high HBV replication characterized by high HBV DNA levels in chronic HBV
      patients. These results suggest a potential prognostic value for disease outcome
      evaluation.

PMID- 25619306
TI  - Resemblance between two relatives - animal and plant breeding.

PMID- 25619307
TI  - Sequence diversity and molecular evolutionary rates between buffalo and cattle.
AB  - Identification of genes of importance regarding production traits in buffalo is
      impaired by a paucity of genomic resources. Choice to fill this gap is to exploit
      data available for cow. The cross-species application of comparative genomics
      tools is potential gear to investigate the buffalo genome. However, this is
      dependent on nucleotide sequences similarity. In this study, gene diversity
      between buffalo and cattle was determined using 86 gene orthologues. There was
      approximately 3% difference in all genes in terms of nucleotide diversity and
      0.267 +/- 0.134 in amino acids, indicating the possibility for successfully using
      cross-species strategies for genomic studies. There were significantly higher non
      synonymous substitutions both in cattle and buffalo; however, there was similar
      difference in terms of dN- dS (4.414 versus 4.745) in buffalo and cattle,
      respectively. Higher rate of non-synonymous substitutions at similar level in
      buffalo and cattle indicated a similar positive selection pressure. Results for
      relative rate test were assessed with the chi-squared test. There was no
      significance difference on unique mutations between cattle and buffalo lineages
      at synonymous sites. However, there was a significance difference on unique
      mutations for non-synonymous sites, indicating ongoing mutagenic process that
      generates substitutional mutation at approximately the same rate at silent sites.
      Moreover, despite of common ancestry, our results indicate a different divergent
      time among genes of cattle and buffalo. This is the first demonstration that
      variable rates of molecular evolution may be present within the family Bovidae.

PMID- 25619308
TI  - Non-alcoholic fatty liver disease comorbid with major depressive disorder: The
      pathological features and poor therapeutic efficacy.
AB  - BACKGROUND AND AIM: Major depressive disorder (MDD) is an important public health
      problem, and it is often comorbid with many chronic diseases. The purpose of this
      study was to identify the clinical features of non-alcoholic fatty liver disease
      (NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the
      effect of treatment in patients with NAFLD. METHODS: A total of 258 patients with
      biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of
      the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text
      revision. The patients were followed up for 48 weeks under standard care for
      NAFLD, which consisted mainly of lifestyle modification. RESULTS: There were 32
      patients comorbid with MDD. They were characterized by more severe histological
      steatosis and higher NAFLD activity score, and also significantly higher levels
      of serum aminotransferase, gamma-glutamyl transpeptidase and ferritin, than age
      and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD
      showed poor response to the standard care for NAFLD, in body weight loss and in
      other parameters. Particularly, NAFLD patients with unstable MDD (not in
      full/partial remission) showed severe resistance to the treatment. CONCLUSION:
      This is the first study to demonstrate the clinical features and response to
      therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was
      associated with more severe histological liver steatosis and worse treatment
      outcomes in patients with NAFLD. Further investigations are required to develop
      new lifestyle modification programs that enable NAFLD patients with MDD to
      achieve the treatment goal.

PMID- 25619309
TI  - PVC-Induced Second Tachycardia.

PMID- 25619310
TI  - Enhancement on reactive oxygen species and COX-1 mRNA levels modulate the
      vascular relaxation induced by sodium nitroprusside in denuded mice aorta.
AB  - This study aimed to investigate the modulation of nitric oxide/reactive oxygen
      species in sodium nitroprusside relaxation in mice aorta. Sodium nitroprusside
      induced relaxation in endothelium-intact (e+) and endothelium-denuded (e-) aortas
      with greater potency in e+ than in e-. The nitric oxide synthase inhibitor did
      not alter the sodium nitroprusside relaxation in both e+ and e- aortas. However,
      the superoxide anion scavenger abolished the difference in sodium nitroprusside
      potency between e+ and e-. Sodium nitroprusside reduced dihydroethidium-derived
      fluorescent products in both groups; however, the difference between intact and
      denuded mice aorta remains. The glutathione levels and basal antioxidant activity
      of superoxide dismutase were reduced in e- aorta when compared with e+, and these
      values were not altered by sodium nitroprusside. Confirming these results, the
      levels of lipid peroxidation in e+ were significantly lower when compared to e-,
      and these values were not altered by sodium nitroprusside. The sodium
      nitroprusside potency in the presence of a nonselective COX inhibitor or the
      EP/DP prostaglandin receptor antagonist in endothelium denuded was similar to
      that in intact mice aorta. Based on these results, we performed the COX-1 and COX
      2 mRNA level studies, and in denuded mice aorta, there was an upregulation in COX
      1 mRNA levels. Taken together, our findings show that in the absence of
      endothelium, there is an enhancement of superoxide levels, leading to GSH
      consumption and higher levels of lipid peroxidation, showing an intense redox
      status. Furthermore, in denuded mice aorta, there was an upregulation of COX-1
      mRNA expression, leading to vasoconstrictor prostanoids synthesis. The
      interaction of vasoconstrictor prostanoids with its receptors EP/DP negatively
      modulates the vascular relaxation induced by SNP in denuded mice aorta. 

PMID- 25619312
TI  - Morphological and molecular variation in the least madtom Noturus hildebrandi
      (Siluriformes: Ictaluridae), a Mississippi Embayment endemic: evidence for a
      cryptic lineage in the Hatchie River.
AB  - Sheared principal component analysis of 40 morphometric characteristics measured
      for 146 individuals and relative frequencies of pigmentation patterns scored for
      980 individuals of the least madtom Noturus hildebrandi, a diminutive catfish
      endemic to eastern lowland drainages of the Mississippi Embayment region of North
      America, suggested a clinal pattern of morphological variation extending across
      the range from north to south. DNA sequence data representing 90 individuals from
      the mitochondrial gene cytochrome b (cytb) analysed using Bayesian phylogenetic
      methods recovered four major haplotype clades, suggestive of a high degree of
      isolation by drainage. Individual gene trees of cytb and four additional nuclear
      loci as well as trees based on concatenated datasets of these genes consistently
      recovered a cryptic lineage of individuals from the Hatchie River drainage that
      is morphologically indistinguishable from surrounding populations. Gene-tree
      analyses failed to recover a monophyletic N. hildebrandi with respect to Noturus
      baileyi. A coalescence-based species tree analysis, however, did recover N.
      hildebrandi monophyly with high support, suggesting that relationships reflected
      in individual gene trees and concatenated datasets are in part artefacts of
      incomplete lineage sorting or an ancient introgressive event. Results are
      consistent with the hypothesis of an ancient connection between the Hatchie and
      Tennessee River systems. Current subspecific designations are of limited utility
      as they reflect morphological variation and are not entirely consistent with
      phylogeny. Discrepancies between the pattern of variation observed in the
      morphological and molecular data may be explained by recent local adaptation to
      individual stream conditions that masks deeper evolutionary divergences.

PMID- 25619313
TI  - Association between CYP1B1 gene polymorphisms and risk factors and susceptibility
      to laryngeal cancer.
AB  - BACKGROUND: The aim of this study was to investigate the association between
      polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene,
      and the susceptibility to laryngeal cancer among the Chinese Han population.
      MATERIAL/METHODS: In a case-control study, we investigated polymorphisms in the
      CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative
      polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300
      Chinese Han patients with laryngeal cancer and 300 healthy Chinese Han subjects
      in a control group. We also studied the interactions between genetic polymorphism
      and risk factors such as smoking and alcohol consumption in the pathogenesis of
      laryngeal cancer. RESULTS: There were statistically significant differences in
      the distributions of the rs1056827 and rs1056836 genotypes between the 2 groups.
      Regarding rs1056827, carriers of the T allele had a significantly higher risk of
      laryngeal cancer than the G-allele carriers (OR=1.4339, 95% CI: 1.1268-1.8247;
      P=0.0034). The difference was still statistically significant after adjusting for
      factors such as age, sex, smoking, and drinking (adjusted OR=1.743, 95% CI: 1.124
      3.743, P<0.001). However, regarding rs1056836, the G allele carriers had a
      significantly lower risk of laryngeal cancer than the C allele carriers
      (OR=0.5557, 95% CI: 0.3787-0.8154; P=0.0027). The difference was statistically
      significant even after adjusting for factors such as age, sex, smoking, and
      drinking (adjusted OR=0.5641, 95% CI: 0.3212-0.8121, P=0.001). Subjects who carry
      the C-T-C haplotype have a significantly increased incidence of laryngeal cancer.
      We also found that CYP1B1 rs1056827 polymorphism had synergistic effects with
      smoking or alcohol consumption regarding the risk of laryngeal cancer.
      CONCLUSIONS: CYP1B1 gene polymorphism is closely related to the onset of
      laryngeal cancer. There is a mutually synergistic effect between smoking, alcohol
      consumption, and CYP1B1 gene polymorphisms regarding laryngeal cancer.

PMID- 25619314
TI  - High light-induced hydrogen peroxide production in Chlamydomonas reinhardtii is
      increased by high CO2 availability.
AB  - The production of reactive oxygen species (ROS) is an unavoidable part of
      photosynthesis. Stress that accompanies high light levels and low CO2
      availability putatively includes enhanced ROS production in the so-called Mehler
      reaction. Such conditions are thought to encourage O2 to become an electron
      acceptor at photosystem I, producing the ROS superoxide anion radical (O2.-) and
      hydrogen peroxide (H2 O2 ). In contrast, here it is shown in Chlamydomonas
      reinhardtii that CO2 depletion under high light levels lowered cellular H2 O2
      production, and that elevated CO2 levels increased H2 O2 production. Using
      various photosynthetic and mitochondrial mutants of C. reinhardtii, the
      chloroplast was identified as the main source of elevated H2 O2 production under
      high CO2 availability. High light levels under low CO2 availability induced
      photoprotective mechanisms called non-photochemical quenching, or NPQ, including
      state transitions (qT) and high energy state quenching (qE). The qE-deficient
      mutant npq4 produced more H2 O2 than wild-type cells under high light levels,
      although less so under high CO2 availability, whereas it demonstrated equal or
      greater enzymatic H2 O2 -degrading capacity. The qT-deficient mutant stt7-9
      produced the same H2 O2 as wild-type cells under high CO2 availability.
      Physiological levels of H2 O2 were able to hinder qT and the induction of state
      2, providing an explanation for why under high light levels and high CO2
      availability wild-type cells behaved like stt7-9 cells stuck in state 1. 

PMID- 25619315
TI  - Clinical associations of host genetic variations in the genes of cytokines in
      critically ill patients.
AB  - Host genetic variations may influence a changing profile of biochemical markers
      and outcome in patients with trauma/injury. The objective of this study was to
      assess clinical associations of single nucleotide polymorphisms (SNPs) in the
      genes of cytokines in critically ill patients. A total of 430 patients were
      genotyped for SNPs in the genes of pro- (IL1B, IL6, IL8) and anti-inflammatory
      (IL4, IL10, IL13) cytokines. The main end-points were sepsis, mortality and adult
      respiratory distress syndrome (ARDS). We evaluated the dynamic levels of
      bilirubin, blood urea nitrogen, creatine kinase, creatinine and lactate
      dehydrogenase in five points of measurements (between 1 and 14 days after
      admission) and correlated them with SNPs. High-producing alleles of
      proinflammatory cytokines protected patients against sepsis (IL1B -511A and IL8 
      251A) and mortality (IL1B -511A). High-producing alleles of anti-inflammatory
      cytokines IL4 -589T and IL13 431A (144Gln) were less frequent in ARDS patients.
      The carriers of IL6 -174C/C genotypes were prone to the increased levels of
      biochemical markers and acute kidney and liver insufficiency. Genotype-dependent
      differences in the levels of biochemical indicators gradually increased to a
      maximal value on the 14th day after admission. These findings suggest that
      genetic variability in pro- and anti-inflammatory cytokines may contribute to
      different clinical phenotypes in patients at high risk of critical illness.

PMID- 25619316
TI  - A multidisciplinary approach to an unusual medical case of locally advanced
      gastric cancer: a case report.
AB  - INTRODUCTION: Complete abdominal wall infiltration with neoplastic
      gastrocutaneous fistula is an unexpected and out of the ordinary presentation of
      locally advanced gastric cancer. It is very rare to encounter case reports
      presenting diffuse abdominal wall invasion, but a complete parietal destruction
      is an exceptional event. CASE PRESENTATION: Here we describe the case of an 81
      year-old Caucasian woman presenting a carcinoma perforating her anterior gastric
      wall and infiltrating all layers of her abdominal wall. The gastric tumor
      infiltrated her transverse mesocolon, the rectus abdominis muscles bilaterally
      and overran them anteriorly, causing a large parietal deficit and a complete
      external fistula. Treatment consisted of a complex surgical procedure requiring
      general and reconstructive surgery cooperation in order to perform an en bloc
      gastric resection including colon and abdominal wall, followed by a parietal
      reconstruction through positioning of prosthesis and reverse abdominoplasty.
      CONCLUSIONS: Clinical presentation, histology and therapeutic options are
      discussed. The importance of a multidisciplinary approach when encountering
      extremely rare clinical presentations is emphasized.

PMID- 25619318
TI  - Non-invasive evaluation of liver fibrosis: More well-validated tests available
      for patient management.

PMID- 25619317
TI  - Adverse drug reactions in special populations - the elderly.
AB  - The International Conference on Harmonization considers older people a 'special
      population', as they differ from younger adults in terms of comorbidity,
      polypharmacy, pharmacokinetics and greater vulnerability to adverse drug
      reactions (ADRs). Medical practice is often based on single disease guidelines
      derived from clinical trials that have not included frail older people or those
      with multiple morbidities. This presents a challenge caring for older people, as
      drug doses in trials may not be achievable in real world patients and risks of
      ADRs are underestimated in clinical trial populations. The majority of ADRs in
      older people are Type A, potentially avoidable and associated with commonly
      prescribed medications. Several ADRs are particularly associated with major
      adverse consequences in the elderly and their reduction is therefore a clinical
      priority. Falls are strongly associated with benzodiazepines, neuroleptics,
      antidepressants and antihypertensives. There is good evidence for medication
      review as part of a multifactorial intervention to reduce falls risk in community
      dwelling elderly. Multiple medications also contribute to delirium, another
      multifactorial syndrome resulting in excess mortality particularly in frail older
      people. Clostridium difficile associated with use of broad spectrum antibiotics
      mainly affects frail older people and results in prolonged hospital stay with
      substantial morbidity and mortality. Antipsychotics increase the risk of stroke
      by more than three-fold in patients with dementia. Inappropriate prescribing can
      be reduced by adherence to prescribing guidelines, suitable monitoring and
      regular medication review. Given the heterogeneity within the older population,
      providing individualized care is pivotal to preventing ADRs. 

PMID- 25619319
TI  - Association between smoking and depression in patients with type 2 diabetes: A
      Response.

PMID- 25619320
TI  - The tracheobronchial foreign body in welder without the history of allotriophagy
      and foreign body aspiration.
AB  - The typical chest computed tomography (CT) finding of the arc welders is ill
      defined micronodules diffusely distributed in the lung. We report a rare case of
      tracheobronchial foreign body in welder without the history of allotriophagy and
      foreign body aspiration. We used the CT and mineralogical analysis in diagnosis
      and the flexible fiberoptic bronchoscope in therapy. The CT showed bronchiectasis
      with pulmonary infiltration of the right lower lobe and high-density shadow in
      the basal bronchus of the right lower lobe. The foreign bodies were removed by a
      fibreoptic bronchoscope. Semiquantitative chemical analyses showed that the
      constituent of foreign body was similar to the dregs which were collected in the
      same garage. This is an unusual case of the welding-related respiratory diseases,
      which is different from Welder's siderosis and broncholith. 

PMID- 25619322
TI  - Acute shear stress direction dictates adherent cell remodeling and verifies shear
      profile of spinning disk assays.
AB  - Several methods have been developed to quantify population level changes in cell
      attachment strength given its large heterogeneity. One such method is the
      rotating disk chamber or 'spinning disk' in which a range of shear forces are
      applied to attached cells to quantify detachment force, i.e. attachment strength,
      which can be heterogeneous within cell populations. However, computing the exact
      force vectors that act upon cells is complicated by complex flow fields and
      variable cell morphologies. Recent observations suggest that cells may remodel
      their morphology and align during acute shear exposure, but contrary to
      intuition, shear is not orthogonal to the radial direction. Here we theoretically
      derive the magnitude and direction of applied shear and demonstrate that cells,
      under certain physiological conditions, align in this direction within minutes.
      Shear force magnitude is also experimentally verified which validates that for
      spread cells shear forces and not torque or drag dominate in this assay, and
      demonstrates that the applied force per cell area is largely independent of
      initial morphology. These findings suggest that direct quantified comparison of
      the effects of shear on a wide array of cell types and conditions can be made
      with confidence using this assay without the need for computational or numerical
      modeling. 

PMID- 25619323
TI  - Aboriginal deaths: the gap persists in surgical mortality.

PMID- 25619324
TI  - First-day nerves.

PMID- 25619325
TI  - Response to Re: Enhanced recovery after surgery and laparoscopic colorectal
      surgery: where to now?

PMID- 25619326
TI  - Re: Enhanced recovery after surgery and laparoscopic colorectal surgery: where to
      now?

PMID- 25619327
TI  - Prevalence of duplicate gallbladder in cholecystectomy patients.

PMID- 25619328
TI  - Re: Lateral cervical cysts: an Australian perspective.

PMID- 25619329
TI  - Case of necrotizinig fasciitis in thigh after transobturator tape procedure,
      treated by vacuum-assisted closure.

PMID- 25619331
TI  - Hierarchical ZnO nanorods on Si micropillar arrays for performance enhancement of
      piezoelectric nanogenerators.
AB  - Enhanced output power from a ZnO nanorod (NR)-based piezoelectric nanogenerator
      (PNG) is demonstrated by forming a heterojunction with Si micropillar (MP) array.
      The length of the SiMP array, which was fabricated by electrochemical etching,
      was increased systematically from 5 to 20 MUm by controlling the etching time.
      Our structural and optical investigations showed that the ZnO NRs were grown
      hierarchically on the SiMPs, and their crystalline quality was similar regardless
      of the length of the underlying SiMPs. The peak output voltage from the ZnO NR
      based PNG was greatly increased by ~5.7 times, from 0.7 to 4.0 V, as the length
      of the SiMP arrays increased from 0 (flat substrate) to 20 MUm. The enhancement
      mechanism was explained based on the series connection of the ZnO NRs regarded as
      a single source of piezoelectric potential by creating a heterojunction onto the
      SiMP arrays. 

PMID- 25619330
TI  - Rationally engineered flavin-dependent oxidase reveals steric control of dioxygen
      reduction.
AB  - The ability of flavoenzymes to reduce dioxygen varies greatly, and is controlled
      by the protein environment, which may cause either a rapid reaction (oxidases) or
      a sluggish reaction (dehydrogenases). Previously, a 'gatekeeper' amino acid
      residue was identified that controls the reactivity to dioxygen in proteins from
      the vanillyl alcohol oxidase superfamily of flavoenzymes. We have identified an
      alternative gatekeeper residue that similarly controls dioxygen reactivity in the
      grass pollen allergen Phl p 4, a member of this superfamily that has glucose
      dehydrogenase activity and the highest redox potential measured in a flavoenzyme.
      A substitution at the alternative gatekeeper site (I153V) transformed the enzyme
      into an efficient oxidase by increasing dioxygen reactivity by a factor of
      60,000. An inverse exchange (V169I) in the structurally related berberine bridge
      enzyme (BBE) decreased its dioxygen reactivity by a factor of 500. Structural and
      biochemical characterization of these and additional variants showed that our
      model enzymes possess a cavity that binds an anion and resembles the 'oxyanion
      hole' in the proximity of the flavin ring. We showed also that steric control of
      access to this site is the most important parameter affecting dioxygen reactivity
      in BBE-like enzymes. Analysis of flavin-dependent oxidases from other
      superfamilies revealed similar structural features, suggesting that dioxygen
      reactivity may be governed by a common mechanistic principle. DATABASE:
      Structural data are available in PDB database under the accession numbers 4PVE,
      4PVH, 4PVJ, 4PVK, 4PWB, 4PWC and 4PZF.

PMID- 25619332
TI  - Recurrence prediction in oral cancers: a serum Raman spectroscopy study.
AB  - High mortality rates associated with oral cancers can be primarily attributed to
      the failure of current histological procedures in predicting recurrence.
      Identifying recurrence related factors can lead to improved prognosis, optimized
      treatment and enhanced overall outcomes. Serum Raman spectroscopy has previously
      shown potential in the diagnosis of cancers, such as head and neck, cervix,
      breast, oral cancers, and also in predicting treatment response. In the present
      study, serum was collected from 22 oral cancer subjects [with recurrence (n = 10)
      and no-recurrence (n = 12)] before and after surgery and spectra were acquired
      using a Raman microprobe coupled with a 40* objective. Spectral acquisition
      parameters were as follows: lambdaex = 785 nm, laser power = 30 mW, integration
      time: 12 s and averages: 3. Data was analyzed in a patient-wise approach using
      unsupervised PCA and supervised PC-LDA, followed by LOOCV. PCA and PC-LDA
      findings suggest that recurrent and non-recurrent cases cannot be classified in
      before surgery serum samples; an average classification efficiency of ~78% was
      obtained in after-surgery samples. Mean and difference spectra and PCA loadings
      indicate that DNA and protein markers may be potential spectral markers for
      recurrence. RS of post surgery serum samples may have the potential to predict
      the probability of recurrence in clinics, after prospective large-scale
      validation. 

PMID- 25619334
TI  - Switching of the photophysical properties of Bodipy-derived trans
      bis(tributylphosphine) Pt(II) bisacetylide complexes with rhodamine as the acid
      activatable unit.
AB  - A rhodamine moiety was used for the preparation of trans bis(tributylphosphine)
      Pt(II) bisacetylide complexes (RH-BDPY-Pt-1 and RH-BDPY-Pt-2, with two different
      Bodipy acetylide ligands), which show acid/base-switchable photophysical
      properties. The rhodamine moiety undergoes reversible spirolactam <-> opened
      amide structure transformation in the presence of an acid/base. Bodipy ligands
      are responsible for strong visible light-harvesting. The photophysical properties
      of the Pt(II) complexes were studied with steady state UV-Vis absorption,
      luminescence spectra, nanosecond transient absorption spectroscopy,
      electrochemical characterization and DFT/TDDFT computations. In the absence of an
      acid, the complexes show the absorption of Bodipy ligands at 580 nm and 500 nm,
      respectively. Both complexes show fluorescence. A minor phosphorescence band was
      observed for RH-BDPY-Pt-1. In the presence of trifluoroacetic acid (TFA), the
      spirolactam -> opened amide transformation occurred and the absorption of the
      rhodamine moiety at 570 nm appeared; colour changes were observed for the
      solutions of the complexes. Moreover, the fluorescence of the complexes was
      switched on. Long-lived triplet excited states were observed for the two
      complexes (35 MUs and 423 MUs, respectively, in dichloromethane). Upon the
      addition of TFA, the triplet state lifetime of RH-BDPY-Pt-1 was substantially
      prolonged to 80 MUs from 35 MUs (the triplet state of RH-BDPY-Pt-1 is localized
      on the Bodipy moiety); for RH-BDPY-Pt-2, however, the triplet state is switched
      from the Bodipy-confined triplet state to a triplet state delocalized on the
      Bodipy and rhodamine moiety. Thus both the singlet excited state and the triplet
      state of the Pt(II) complexes were switched upon the addition of an acid. The
      photophysical properties were rationalized with DFT/TDDFT calculations. These
      results on tuning of the photophysical properties of Pt(II) complexes with a
      rhodamine moiety may be useful for designing external stimuli-activatable
      transition metal complexes.

PMID- 25619333
TI  - Essential nurse practitioner business knowledge: An interprofessional
      perspective.
AB  - PURPOSE: To describe business practice knowledge from the perspectives of nurse
      practitioners (NPs) who are practicing clinicians, academic instructors, and
      clinic managers. DATA SOURCE: Using the eight domains of business practice
      attitudes identified by the Medical Group Management Associations Body of
      Knowledge (MGMA), which are supported by the American Association of Colleges of
      Nursing (AACN), a study-specific survey was developed. Data, which describe the
      knowledge and attitudes with respect to business practices, were obtained from
      370 participants. CONCLUSION: Regardless of their job classification, these
      participants described (1) quality management, (2) risk management, and (3)
      patient care systems as critical business practice knowledge. Consensus was also
      achieved when ranking the content for business practice knowledge: (1) patient
      care systems, (2) business operation, and (3) financial management. IMPLICATIONS
      FOR PRACTICE: These data identify gaps in business practice knowledge and content
      that should be included in educational programs. Business practice knowledge is
      essential for a successful clinical practice and should be a professional
      practice skill for the NP.

PMID- 25619335
TI  - Sequential analysis of the normal fetal fissures with three-dimensional
      ultrasound: a longitudinal study.
AB  - OBJECTIVE: To perform a sequential analysis of the main cortical fissures in
      normal fetuses using 3D ultrasound. METHODS: A cohort of patients with
      uncomplicated singleton pregnancies underwent three consecutive transabdominal
      scans at 19-21, 26-28 and 30-34 weeks. Volumes of the fetal head were acquired
      and searched in the multiplanar mode for the following cortical fissures:
      sylvian, parieto-occipital, calcarine, hippocampus and cingulate. A qualitative
      analysis of these sulci was performed in each volume by an experienced operator
      (A) and a trainee (B). By placing the dot on the sulcus in one plane, it was
      evaluated whether it was visible also in other planes. RESULTS: Fifty patients
      were included in the study. At 19-21 weeks, the sylvian and parieto-occipital
      sulci were visualized on at least one plane by both operators in all cases. At 26
      28 weeks, all fissures were visualized by both operators on at least one plane,
      with no significant difference between the performances of the two operators. At
      30-34 weeks, a mild overall decline in the accuracy of identification of all the
      cerebral fissures was observed. CONCLUSIONS: 3D multiplanar mode allows a
      systematic evaluation of the cortical fissures in normal fetuses since
      midtrimester.

PMID- 25619336
TI  - Activatable photodynamic destruction of cancer cells by NIR dye/photosensitizer
      loaded liposomes.
AB  - The phototoxicity of Chlorin e6 (Ce6) for photodynamic therapy (PDT) was found to
      be effectively suppressed by indocyanine green (ICG), a near infrared (NIR) dye.
      Upon NIR laser irradiation at 808 nm, ICG in the liposomes containing ICG and Ce6
      could be degraded, while the phototoxicity of Ce6 could be recovered. In
      addition, we demonstrate that this newly developed liposomal component can be
      successfully used for activatable PDT to destroy cancer cells in vitro. 

PMID- 25619337
TI  - Hollow mesoporous carbon cubes with high activity towards the electrocatalytic
      reduction of oxygen.
AB  - Hollow-structured mesoporous carbon cubes (HMCCs) have been successfully
      synthesized from carbon dioxide by a facile approach based on thermal reduction
      of magnesium. The approach is economical and applicable to large-scale synthesis.
      Notably, pyrrole-type nitrogen species are doped into the HMCCs during the
      synthesis in situ, that is, without introducing a nitrogen-containing precursor.
      A formation mechanism of the HMCCs is proposed, and formation of the structure is
      attributed to MgO templates generated in situ. Furthermore, the HMCCs are
      demonstrated to be a promising alternative to commercial Pt/C fuel-cell catalysts
      for the electrochemical oxygen reduction reaction. 

PMID- 25619338
TI  - Emerging enzymes for ATP regeneration in biocatalytic processes.
AB  - Adenosine-5'-triphosphate-dependent enzyme catalysed reactions are widespread in
      nature. Consequently, the enzymes involved have an intrinsic potential for use in
      syntheses of high value products. Although regeneration systems for ATP starting
      from adenosine-5'-diphosphate are available, certain limitations exist for both
      in vitro and in vivo applications requiring ATP regeneration from adenosine-5'
      monophosphate, or adenosine. Following a short overview of the chemical and
      thermodynamic background, this Minireview focuses on emerging enzymes and
      methodologies for ATP regeneration. A large range of as yet unexploited reactions
      will be accessible with new, powerful, multistep ATP regeneration systems that
      use cheap phosphate donors and provide high longevity, compatibility, and
      robustness under process conditions. Their potential might go far beyond the
      direct use of ATP in enzymatic reactions; enzyme discovery, and engineering, as
      well as immobilisation strategies, will help to realise such systems. 

PMID- 25619339
TI  - Differential response of cholesterol based pyrimidine systems with oxyethylene
      type spacers to gelation and mesogen formation in the presence of alkali metal
      ions.
AB  - A new series of lipophilic cholesteryl derivatives of 2,4,6-trichloro-pyrimidine
      5-carbaldehyde has been synthesized. Oxyethylene spacers of variable lengths were
      inserted between the hydrogen bonding promoting pyrimidine core and the
      cholesteryl tail in order to understand their effect on the self-assembly of
      these compounds. Only compound 1a with the shortest spacer formed a gel in
      organic solvents such as n-butanol and n-dodecane. While other members (1b and c)
      having longer spacers led to sol formation and precipitation in n-butanol and n
      dodecane respectively. The self-assembly phenomena associated with the gelation
      process were investigated using temperature-dependent UV-Vis and CD-spectroscopy.
      The morphological features of the freeze-dried gels obtained from different
      organic solvents were examined by scanning electron microscopy (SEM) and atomic
      force microscopy (AFM). The solid phase behaviours of these molecules and their
      associated alkali metal ion complexes were explored using polarized optical
      microscopy (POM) and differential scanning calorimetry (DSC). The molecular
      arrangements in the xerogel and in the solid state were further probed using a
      wide-angle X-ray diffraction (WAXD) technique. Analysis of the wide-angle X-ray
      diffraction data reveals that this class of molecules adopts a hexagonal columnar
      organization in the gel and in the solid state. Each slice of these hexagonal
      columnar structures is composed of a dimeric molecular-assembly as a building
      block. Significant changes in the conformation of the oxyethylene chains could be
      triggered via the coordination of selected alkali metal ions. This led to the
      production of interesting metal ion promoted mesogenic behaviour.

PMID- 25619340
TI  - Diagnostic accuracy of Narrow Band Imaging for the detection of oral potentially
      malignant disorders.
AB  - OBJECTIVE: To determine the clinical diagnostic accuracy of Narrow Band
      Imaging(TM) for the detection of oral potentially malignant disorders in a
      prospective series of patients. MATERIALS AND METHODS: New and existing patients
      referred to an oral medicine and pathology specialist clinic for assessment of at
      least one white, red or red-white oral mucosal lesion underwent conventional oral
      examination, followed by examination with the white light mode and then narrow
      band imaging mode of a Narrow Band Imaging(TM) system. The clinical presentation,
      microvascular architecture and relevant histopathology of all lesions were
      recorded. RESULTS: A total of 272 lesions from 95 patients were observed. The
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy for the detection of oral potentially malignant disorders or worse
      by Narrow Band Imaging(TM) were 100%, 74.63%, 92.38%, 100% and 93.77%,
      respectively, when compared with conventional oral examination. Narrow Band
      Imaging(TM) aided the detection of 24 lesions undetected by conventional oral
      examination and 13 lesions undetected by white light endoscopy. CONCLUSION:
      Narrow Band Imaging(TM) demonstrates great utility as a visualisation adjunct for
      detecting and monitoring oral potentially malignant diseases, particularly
      lesions not identified by conventional oral examination or white light
      examination alone.

PMID- 25619342
TI  - [New interpretation of autoinflammatory diseases].

PMID- 25619341
TI  - [Primary immunodeficiency diseases: challenges and opportunities for Chinese
      pediatrician].

PMID- 25619343
TI  - [Clinical characteristics and treatment responses of X-linked thrombocytopenia].
AB  - OBJECTIVE: To analyze the clinical and molecular characteristics of patients with
      X-linked thrombocytopenia (XLT) and their responsiveness to treatment with
      various doses of corticosteroids or intravenous immunoglobulin (IVIG) separately.
      METHOD: Data from 15 XLT patients who were hospitalized in Children's Hospital
      Affiliated to Chongqing Medical University from March 2010 to July 2014 were
      analyzed retrospectively, including clinical manifestations, scores, peripheral
      blood, immunological functions, responses to IVIG and steroid treatment with
      various doses and duration. RESULT: All 15 XLT patients met the inclusion
      criteria and showed microthrombocytopenia with or without mild-to-moderate eczema
      or minor infections. Platelet counts ranged from (8-80) * 109/L. The platelet
      volume value ranged between 5.6 and 10.9 fl (normal range: 9.4-12.5 fl). Raised
      serum IgG was found in 5 cases, while low serum IgG was found in 2 cases. WAS
      gene analysis revealed missense mutations in 14 patients, including 4 hotspots
      (V75M, R86C, R86H, R86L) and 1 novel mutation (Y107C). Flow cytometer analysis of
      13 patients showed various amounts of WAS protein (WASP) expression, 2 patients
      had normal amounts of WASP expression, 5 had reduced amounts, and 6 had absent
      WASP expression. Their responses to individual steroid and IVIG treatment with
      various doses and duration were also reviewed. Fourteen patients who were
      misdiagnosed as immune thrombocytopenic purpura at first received 28 courses of
      steroids and (or) 47 courses of IVIG treatment. The post-treatment platelet
      counts of 1 000-2 000 mg/(kg * d) IVIG(25 courses) at 2-7 d and 8-14 d time
      points were (60 +/- 10) * 109/L and (41 +/- 7) * 109/L, which indicate a
      significantly better responsiveness than those by [(31 +/- 7) * 109/L, (21 +/- 2)
      * 109/L] of 400-500 mg/(kg.d) IVIG(22 courses) (Z = -4.419, -1.592;P =
      0.002,0.011). However, there were no significant differences between the
      responsiveness of 3 doses [1-2 mg/(kg.d)(8 courses), 3-6 mg/(kg.d) (11 courses)
      and 20-30 mg/(kg * d)(9 courses)] of steroids (F = 0.387,0.252;P = 0.980,0.761)
      at 2-7 d and 8-14 d time points. The platelet counts gradually decreased to the
      primary level at 15-30 d after any doses of steroids and (or) IVIG treatment. The
      effective rate of 1 000-2 000 mg/(kg * d) IVIG treatment was 18/25, which was
      significantly higher than that (2/22) of 400-500 mg/(kg * d) (chi2 = 9.836, P =
      0.008). The effective rate of 20-30 mg/(kg * d) steroids treatment (7/9) was
      relatively higher than 1-2 mg/(kg * d) (4/8) and 3-6 mg/(kg * d) (6/11) with no
      significant difference (chi9 = 3.235, P = 0.581). After the treatment with
      steroids and /or IVIG 14 cases with hemorrhage were all improved. CONCLUSION: The
      clinical characteristics of X-linked thrombocytopenia were microthrombocytopenia
      with or without mild-to-moderate eczema or minor infections. WAS gene and WASP
      analysis were diagnostic methods. There were no significant differences between
      the responsiveness of 3 doses of steroids; 1 000-2 000 mg/(kg.d) IVIG had a
      significantly better responsiveness. However, IVIG and steroids with any dose and
      duration may only transiently increase peripheral platelet level of XLT patients.

PMID- 25619344
TI  - [Mutations of NOD2 gene and clinical features in Chinese Blau syndrome patients].
AB  - OBJECTIVE: Blau syndrome (BS), an autosomal dominant inherited autoinflammatory
      disease, is caused by NOD2 mutations. This study aimed to analyze NOD2 gene of
      suspected BS patients to make definite diagnosis, find NOD2 mutation types and
      clinical features of Chinese BS cases, and find some clinical indications to
      identify BS by comparing BS and non-BS cases. METHOD: Eighteen suspected BS
      children (7 boys and 11 girls, age of first visit was from 1 y 8 m to 9 y 6 m)
      who visited Peking Union Medical College Hospital from 2006 to 2014 and their
      parents's DNA were extracted from 4 ml blood specimens. PCR was performed for
      exon 4 of NOD2 and PCR products were purified by 2% gel electrophoresis and
      sequenced directly. Role of novel missense mutations in pathogenicity was
      analyzed by SIFT and sequencing NOD 2 of fifty normal controls. Clinical data of
      BS children diagnosed by NOD2 analysis were summarized and compared with the data
      of non-BS group. RESULT: (1) Twelve of eighteen suspected BS children were
      diagnosed as BS by NOD2 analysis, and the remaining 6 were excluded. Seven
      missense mutations were detected, 4 were reported before: c.1000C>T, p. Arg
      334Trp; c.1001G>A, p. Arg334Gln; c.1538T>C, p. Met513Thr; c.1759C>T, p.
      Arg587Cys. Three novel mutations were found: c. 1147 G>C, p.Glu383Gln; c.1471A>T,
      p. Met491Leu; c.2006A>G, p.His669Arg. (2) Chronic symmetric arthritis and multi
      joints periarticular hydatoncus, which were painless with fluctuation, were found
      in all 12 BS children with NOD2 mutations. Skin rash, chronic symmetric
      arthritis, and recurrent uveitis were identified in 7 patients. Three patients
      had no skin rash, while 1 had no uveitis, 1 only had symmetric arthritis and
      multi-joints periarticular hydatoncus. Four children inherited the disease from
      father. (3) Compared with other 6 non-BS children, BS children had such different
      clinical characteristic (P < 0.05): All the BS cases had multiple periarticular
      hydatoncus, which always had no persistent fever, most had no elevated CRP, while
      non-BS group always had no hydatoncus, most had persistent fever, all had
      elevated CRP. CONCLUSION: The 12 BS children were diagnosed by NOD2 analysis; 7
      missense mutations were detected, 3 were novel mutations, adding new findings to
      human NOD2 mutations. Although classic BS was characterized by skin rash,
      arthritis, and eye involvement, some presented with less than 3 of the classic
      features. Chronic symmetric arthritis and multi-joints periarticular hydatoncus
      were the most comment fetures. Comparing with non-BS group, all BS cases had
      multi hydatoncus surrounding multi-joints, always had no persistent fever, most
      had no elevated CRP. Those features may distinguish BS in clinical settings.

PMID- 25619345
TI  - [Clinical characteristics of children with Langerhans cell histiocytosis with
      pulmonary involvement].
AB  - OBJECTIVE: To improve the recognition of the clinical presentation and radiologic
      manifestation of children with Langerhans cell histiocytosis (LCH) with pulmonary
      involvement. METHOD: A retrospective analysis was conducted on children who
      presented with respiratory symptoms or abnormal lung radiologic findings, and
      finally diagnosed with LCH in Ward 2 of Divison of Respiratory Diseases, Beijing
      Children's Hospital during the last 4 years. RESULT: Fourteen children (10 boys
      and 4 girls) were included in this study. Male to female ratio was 2.5: 1. The
      median age was 1.3 years. Pulmonary involvements were coexisted with other
      involved organs in all the patients, such as skin (10 cases, 71%), liver (8
      cases, 57%), and bone involvement (7 cases, 50%). The most common symptoms were
      cough and fever (7 cases, 50%). Respiratory symptoms were nonspecific, and 3
      children had no respiratory symptom but abnormal findings on lung high-resolution
      CT (HRCT). The most common HRCT finding was the coexistence of nodules and cysts
      (6 cases, 43%). Other findings include cysts only (5 cases, 36%), nodules only (1
      case), and with neither nodule nor cyst (2 cases, 14%). Pneumothorax was found in
      7% of children. CONCLUSION: Pulmonary involvement in children with LCH is easily
      misdiagnosed, and often coexisted with other involved tissues/organs such as skin
      and liver. Rash, which is easily missed in physical examination is very important
      for the diagnosis of LCH. The characteristic findings of lung HRCT (nodules
      and/or cysts) are helpful for diagnosis.

PMID- 25619346
TI  - [Clinical advance of atypical severe combined immunodeficiency].

PMID- 25619347
TI  - [Thinking of bronchopulmonary dysplasia from "classic" to the "new"
      transformation].

PMID- 25619348
TI  - [Current situation of pediatric emergency in tertiary and teaching hospitals in
      15 provinces, municipalities and autonomous regions in China Mainland].
AB  - OBJECTIVE: Pre-hospital care, emergency department and critical care medicine are
      the key components of emergency medical service system. Two investigations about
      the pediatric critical care medicine in China mainland showed great progress. In
      recent years, most hospitals in China mainland have established emergency
      department, hardware configuration and staff status were gradually standardized.
      But most of the emergency departments mainly provide service to adult patients
      and pediatric emergency medicine lags behind. The purpose of this investigation
      was to understand the current situation and main problems of pediatric emergency
      in China mainland. METHOD: A questionnaire developed by the Subspecialty Group of
      Pediatrics, Chinese Society of Emergency Medicine and the Subspecialty Group of
      Emergency Medicine, Chinese Society of Pediatrics was e-mailed to the members of
      the above-mentioned two subspecialty groups. The contents of the questionnaire
      included 46 items which were divided into 5 categories: the general situation of
      the hospital, the pediatric emergency setting and composition, key equipments and
      techniques, staff status, training program and running data from 2011 to 2012.
      RESULT: Sixty-three questionnaires were delivered and 27 (42.9%) hospitals
      responded which located in 15 different provinces, municipalities and autonomous
      regions. Among the 27 hospitals, 10 (37.0%) had no pediatric resuscitation room;
      25 (92.6%) had no equipments for cardiac output monitor and gastric lavage; 13
      (48.1%) had no bedside fibrolaryngoscope or fiberbronchoscope; 5 (18.5%) had no
      blood gas analyzer; 4 (14.8%) without respirator, defibrillator, bedside
      radiography or ultrasonic equipment; 2 (7.4%) had no neonatal incubator; 9
      (33.3%) could not do intraossous infusion. The average ratio of professional
      emergency pediatricians to all physicians was 43.5%. Twenty hospitals
      incompletely filled in the pediatric emergency running data. CONCLUSION: The main
      problems existing in pediatric emergency include: imperfect pediatric emergency
      settings; short of key equipment; key rescue techniques are not popularized,
      acute shortage of emergency pediatricians and inadequate monitoring and
      management of pediatric emergency. The major ways to solve the predicament in
      pediatric emergency should include: the policy and financial support from
      national and local government; training pediatricians, especially urgent training
      of emergency pediatricians; improving pediatric emergency development and
      management.

PMID- 25619349
TI  - [Central venous-to-arterial carbon dioxide difference in critically ill pediatric
      patients with septic shock].
AB  - OBJECTIVE: To assess the value of central venous-to-arterial carbon dioxide
      difference [ P( cv-a) CO2] in evaluation of disease severity and prognosis in
      children with septic shock who already had central venous oxygen saturation
      (ScvO2) higher than 70% after early resuscitation. METHOD: In this prospective
      study, 48 septic shock children seen in Shanghai Children's Hospital, Shanghai
      Jiao Tong University were enrolled from Jun 2012 to May 2014. 36(75.0%) were
      male, 12 (25.0%) were female, the average age was (31.9 +/- 24.5) months. The
      critically ill patients with septic shock were treated to achieve ScvO2greater
      than 70% depending on early goal-directed therapy (EGDT). All patients were
      divided into two groups, based on P(cv-a)CO2, low P(cv-a)CO2group with P(cv
      a)CO2< 6 mmHg (1 mmHg = 0.133 kPa) and high P(cv-a)CO2group with P(cv-a)CO2>= 6
      mmHg. The parameters of hemodynamics including mean blood pressure (MAP), heart
      rate (HR), central venous pressure (CVP), perfusion-related parameters [ScvO2,
      P(cv-a)CO2, serum lactate (Lac), Lac clearance rate], pediatric critical illness
      score, PRISMIII score, and 28 days in-hospital mortality were recorded for all
      patients. RESULT: Of the 48 cases with septic shock whose ScvO2was higher than
      70%, 17 patients (35.4%) had high P(cv-a)CO2( >= 6 mmHg) and 31 (65.6%) had lower
      P(cv-a)CO2(<6 mmHg). There were no significant differences between the 2 groups
      of patients in age, PRISMIII score and PCIS (P > 0.05 ), but Lac and P(cv
      a)CO2values were significantly different ( P < 0.05). Low P(cv-a) CO2group
      patients had lower 28 days mortality than high P(cv-a) CO2group[11/17 vs. 32.3%
      (10/31), P < 0.05]; 24 h after resuscitation, compared with high P(cv-a)
      CO2group, low P(cv-a) CO2group patients had lower Lac values [(2.0 +/- 1.3) vs.(
      2.7 +/- 1.2) mmol/L, P < 0.05]. Low P(cv-a) CO2group patients had shorter
      duration of vasoactive drugs use [(16 +/- 14) vs. (44 +/- 21)h, P < 0.05], 24 h
      Lac clearance rate was significantly higher for low P(cv-a) CO2group than for
      high P(cv-a) CO2group[ (31 +/- 10) % vs. (26 +/- 6)%, P < 0.05]. CONCLUSION: When
      ScvO2> 70% was achieved after early resuscitation in septic shock children, P(cv
      a) CO2is a sensitive biomarker to assess tissue perfusion, and high P(cv-a)
      CO2group patients had poor outcome.

PMID- 25619350
TI  - [A case of autoimmune lymphoproliferactive syndrome and literature review].
AB  - OBJECTIVE: To summarize the clinical characteristics, diagnosis and treatment of
      a case with autoimmune lymphoproliferative syndrome (ALPS) . METHOD: The patient
      was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being
      admitted to the Department of Rheumatism and Immunology of Tianjin Children's
      Hospital in February 20, 2014. The clinical characteristics, physical
      examination, laboratory tests, gene tests, and treatment process were analyzed
      and related literature was reviewed. RESULT: The patient was a 16-month- old
      boy.Since the first month of life, he started to have repeatedly fever, diarrhea,
      shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L)
      and thrombocytopenia (min 35 * 109/L) . But multiple exams showed a normal
      peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1
      710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow
      cytometric measures showed that CD3+ CD4- CD8- T lymphocytes significantly
      increased ( > 10%) at four times. The count of CD3+ TCRalphabeta+ CD4- CD8-T
      lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed
      that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as
      ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He
      was treated with prednisone 15 mg once daily and immunomodulator 150 mg three
      times a day, while in maintaining period with normal levels of hemoglobin and
      platelet, the dose of prednisone was reduced gradually. Till now, the patient has
      been treated and observed for 8 months. We retrieved the reports of ALPS in the
      databases at home and abroad published in recent 10 years, more than 400 cases
      reported from foreign countries, but there were only 5 domestic cases. Among
      those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented
      servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with
      hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent
      infection, one of them had glomerulonephritis. All patient with significant high
      level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of
      them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5
      cases CD3+ CD4- CD8-T cells > 10%, and in 2 case DNTs were 8.9% and 15.7%
      respectively (the other 3 cases missed the exam). Three cases were clearly
      detected with FAS mutations. All patients were treated with corticosteroid, 2 of
      them were added with mycophenolate mofetil. The therapy presented effective
      result in early 1-3 months, but no long-term follow-up reports were available.
      CONCLUSION: ALPS is a disorder of disrupted lymphocyte homeostasis caused by
      defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency
      diseases. The onset of the disease occurs during infancy mainly. Clinical
      lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be
      associated with frequent infections and allergies. The level of serum vitamin B12
      > 1.5 pg/L and the count of CD3+ CD4- CD8- T cell show important significance.
      Exact diagnosis should depend on detecting DNTs and FAS gene.

PMID- 25619351
TI  - [Role of Th17/Treg imbalance in the immune pathogenesis and treatment of children
      with aplastic anemia].
AB  - OBJECTIVE: To study the role of Th17/Treg imbalance in the immune pathogenesis
      and therapeutic significance in childhood aplastic anemia (AA). METHOD: We
      analyzed data from 43 children (male: female = 14: 29) with AA, all the cases
      were at the age of 2 to 14 years at diagnosis, and were hospitalized at our
      department of pediatrics between January 2012 and October 2013 in the Second
      Hospital of Anhui Medical University. All these patients were divided into 2
      groups, severe AA (SAA) group (n = 25, male: female = 8: 17, 2-14 years old) and
      non-severe AA (NSAA) group (n = 18, male: female = 6: 12, 2-14 years old),
      depending on the severity at first diagnosis. As to the treatment, we analyzed
      data at 3 phases of treatment, diagnosis (n = 43, male: female = 14: 29, 2-14
      years old), transfusion-indenpendence (n = 8, male: female = 5: 3, 2-11 years
      old), complete response (n = 6, male: female = 3: 3, 2-11 years old); at the same
      time, AA children who did not respond to the treatments were considered as failed
      treatment control (transfusion-indenpendence with failed treatment group, n = 5,
      male: female = 1: 4, 3-8 years old; complete response failed treatment group, n =
      4, male: female = 2: 2, 4-11 years old). The ratio of Treg and Th17 cells in
      CD4(+) T cells were tested by flow cytometry. The levels of IL-6 and IL-17 in
      plasma were determined by ELISA. During the same period, 25 age-matched healthy
      children (male: female = 12: 13, 3-14 years old) were recruited as normal
      control, 9 cases (male: female = 5: 3, 2-11 years old) of AA children induced by
      chemotherapy as diagnosis control group. Differences in variables were analyzed
      using ANOVA and t-tests or the Kruskal-Wallis and Mann-Whitney U-tests, as
      appropriate. Correlation analysis was evaluated by the Spearman rank correlation
      test. RESULT: (1) The ratio of Th17 cells in newly diagnosed AA patients were
      higher than that of normal group or diagnosis control group [1.63% (1.27%, 2.48%)
      vs. 0.4% (0.35%, 0.51%) or 0.50% (0.45%, 0.75%), both P < 0.01] while the ratio
      of Treg cells was lower [4.24% (3.10%, 5.29%) vs. 7.03% (6.56%, 7.48%) or 7.50%
      (6.60%, 8.30%), both P < 0.01] and the proportion of Th17/Treg were significantly
      higher [0.53(0.34, 0.69) vs. 0.06 (0.05, 0.07) or 0.09 (0.08,0.11), both P <
      0.01]. (2) The levels of IL-6 and IL-17 in newly diagnosed AA patients were
      higher than in normal group [ (223 +/- 92) vs. (116 +/- 18) ng/L, (26.2 +/- 12.0)
      ng/L vs. (10.6 +/- 2.1) ng/L, P both < 0.01]. There was a positive correlation
      between Th17 cells and some Th17 cells related cytokines such as IL-17 and IL-6
      (r = 0.62, 0.64, P both < 0.01). (3) The ratio of Th17, Th17/Treg, and the levels
      of IL-6 and IL-17 in children with SAA were also higher than in normal group
      [1.80% (1.25%, 2.61%) vs. 0.40% (0.35%, 0.51%), 0.57% (5.10%,0.82%) vs. 0.06%
      (0.05%, 0.07%), (225 +/- 108) vs. (116 +/- 18) ng/L, (25.9 +/- 12.6) vs. (10.6 +/
      2.1)ng/L, all P < 0.01]. NSAA also higher than normal group. The ratio of Treg
      in children with SAA and NSAA was less than that in normal group (P all < 0.01).
      However, the ratio of Th17, Treg, Th17/Treg, and the levels of IL-6 and IL-17 had
      no significant difference between SAA and NSAA (all P > 0.05). (4) In different
      stages of treatment, such as diagnosis, transfusion-indenpendence, complete
      response, there were significant differences in the ratio of Th17 and Th17/Treg
      (both P < 0.05) but not in Treg (P > 0.05). CONCLUSION: The imbalance of
      Th17/Treg cells and abnormally increased cytokines related to Th17 cells exist in
      peripheral blood of AA children, but did not significantly affect the severity of
      AA in preliminary diagnosis. After treatment with immunosuppression, AA was
      gradually relieved as the imbalance of Th17/Treg was corrected.

PMID- 25619352
TI  - [Report of a child with neonatal-onset multisystem inflammatory disease and
      review of the literature].
AB  - OBJECTIVE: Neonatal-onset multisystem inflammatory disease (NOMID) is not widely
      recognized in China. This study aimed to investigate the diagnosis and treatment
      of NOMID. METHOD: To analyze the clinical characteristics and laboratory results
      including skin biopsy, gene analysis and serum interleukin 1beta of a boy
      admitted to Peking University First Hospital in November of 2013. Reports on
      NOMID were searched and the clinical and laboratory characteristics of reported
      cases were summarized. RESULT: The patient was a 1-year-old boy. He had urticaria
      since 2 days after birth, and presented with episodes of fever, aseptic
      meningitis, symptoms of joints, short statue, hearing loss, abnormal fundus
      findings, and leucocytosis, high level of c-reactive protein (CRP) and abnormal
      findings of head MRI including ventriculomegaly and white matter dysplasia.
      Urticaria was confirmed by skin biopsy. Gene analysis showed T1702T/A in exon 4
      of NLRP3 gene, which causes Phe568lle. Serum interleukin 1beta increased
      dramatically. The boy was diagnosed as NOMID. He did not respond to antibiotic
      therapy and anti-allergy therapy. Corticosteroid therapy induced normalization of
      body temperature, and alleviation of rash, but not improvement in cerebrospinal
      fluid cell numbers. After searching reports of NOMID at PubMed, and Chinese
      literature published before November 2013, we summarized cases from 8 reports and
      reviewed 148 cases. The results showed that fever, urticaria, meningitis and
      arthropathy are the most common manifestations of NOMID, only 57% (69/122) of
      patients had mutation of NLRP3. CONCLUSION: This is a rare report of NOMID in
      children in China. Fever, urticaria, aseptic meningitis and persistently high
      level of CRP are characteristics of NOMID. Gene analysis and serum interleukin
      1beta detection can aid in diagnosis.

PMID- 25619353
TI  - [Diagnosis of MECP2 duplication syndrome with molecular genetic techniques].
AB  - OBJECTIVE: To investigate whether the four boys with delayed motor development
      and intellectual disability suffer from MECP 2 duplication syndrome. METHOD:
      Blood specimens and clinical data of four patients and mothers of patient 2 and
      patient 4 were collected. Genomic DNA was extracted from peripheral blood using
      DNA extraction kit. At first multiplex ligation-dependent probe amplification
      (MLPA) was employed in 4 patients, two distinct kits SALSA P036 and P070 for sub
      telomere screening, and SALSA P245 for the 22 common microdeletion and
      microduplication syndromes. Then array-CGH analysis was carried out. Two mothers
      of patients were tested by array- comparative genomic hybridization (CGH) and X
      chromosome inactivation analysis. RESULT: All the 4 patients presented with
      severe hypotonia, delayed motor development, intellectual disability and absent
      or limited language. Three patients manifested recurrent pneumonia in infancy
      except patient 2. Four patients had duplication on chromosome Xq28 with MLPA kit
      SALSA P245. Array-CGH identified the size of each duplication on Xq28. The
      precise size of each duplication was different in the four patients: patient 1,
      14.931 Mb, patient 2, 0.393 Mb, patient 3, 0.482 Mb and patient 4, 0.299 Mb. To
      compare Xq28 duplications with UCSC database (http://genome.ucsc.edu/) revealed
      that each duplication harbors the MECP 2 and HCFC 1 gene. Mothers of patient 2
      and patient 4 also carried microduplication on Xq28. X chromosome inactivation
      analysis demonstrated completely skewed inactivation (0: 100) and it is the
      inactive allele that passed on to the patients. CONCLUSION: For patients that
      present with delayed motor development, intellectual disability, hypotonia,
      absent or limited language and recurrent infection, combination of MLPA and array
      CGH is effective and specific diagnostic methods of MECP 2 duplication syndrome.

PMID- 25619354
TI  - [Children with idiopathic hypogonadotropic hypogonadism: clinical data analysis
      and mutations analysis of KAL1 and FGFR1 gene].
AB  - OBJECTIVE: To summarize the clinical features of idiopathic hypogonadotropic
      hypogonadism (IHH) diagnosed during childhood, and detect mutations in KAL1 and
      FGFR1, acting as key clues for diagnoses. METHOD: We collected and analyzed
      clinical data of 21 cases (including demographic data, chief complaint, history
      of present illness, family history, physical examination, laboratory tests and
      imaging studies, etc.) diagnosed with IHH from December 2008 to February 2013.
      Polymerase chain reaction and gene sequencing was applied to detect mutations on
      KAL1 and FGFR1. Fifty healthy unrelated individuals were choosen as controls.
      RESULT: Of 21 patients with IHH, 19 were males and 2 females, they visited us
      initially from 8-17 years old, with an average of (13.58 +/- 2.38) years old.
      Sixteen cases were KS patients (76%). One boy reported abnormal sense of smelling
      but having olfactory perfect picture on MRI; 2/19 male cases had no puberty when
      they were over 13-14 years old without abnormal external genitalia. 8/19 cases
      only had small penis, 8/19 had both of cryptorchidism and small penis, and the
      Case 2 also had hypospadias. One boy had cryptorchidism combined with a normal
      penis. Only 2 girls diagnosed as IHH who visited us because of no puberty signs
      when they were 13 and 16 years old, respectively. Other clinical manifestations
      included: one with gynecomastia, 2 had mental retardation, and one was deaf; one
      with high palatal arch; one with mirror-movement and one with left renal agenesis
      but normal renal function respectively. Laboratory tests showed that the basic
      testosterone (T) is low and with inappropriately low or normal gonadotropin
      hormones. The results of cases of standard human chorionic gonadotropin (HCG)
      test of 7 cases out of 19 male children's were normal (testosterone>1 100 ng/L),
      and another nine cases continued to complete the extended HCG test, and the
      testosterone levels of two of them (cases 6, 8) were still lower than 1 000 ng/L.
      Family history: the parents in 9/21 family had delayed puberty, involving only
      one parent in 6 families, involving both in 2 families and the other one was an
      uncle having micropenis with a child. Among these 21 cases, only one boy's father
      had hyposmia and his first emission age was 14-15 years. Eleven patients
      accompanied abnormal sense of smelling and the olfactory organ abnormalities on
      MRI, 4 had olfactory organ abnormalities on MRI while they had good smelling
      function self-reportedly. We got 15 samples (12 KS and 3 nIHH cases) to screen
      the mutation of KAL1 (14 exons) and FGFR1 (18 exons). A splicing mutation
      c.1062+1G>A in KAL1 is identified in case 17 with IHH. One novel heterozygous
      FGFR1 mutation, a single base deletion mutation on the exon 1 c.27delC is
      identified in case 14. This mutation causes the premature termination codons.
      CONCLUSION: This pilot research showed that IHH/KS diagnosis in children depends
      on clinical manifestation rather than gene analysis. Small penis or
      cryptorchidism, smelling abnormality and positive familial history may contribute
      to the KS/HH diagnosis. MRI of olfactory bulb acts as important proof for
      diagnosis of KS. Mutations in KAL1 and FGFR1 gene are not main causes of Kallmann
      syndrome.

PMID- 25619355
TI  - [A novel homozygous mutation p.E25X in the HSD3B2 gene causing salt wasting 3beta
      hydroxysteroid dehydrogenases deficiency in a Chinese pubertal girl: a delayed
      diagnosis until recurrent ovary cysts].
AB  - OBJECTIVE: 3beta- hydroxysteroid dehydrogenase deficiency (3betaHSD), a rare form
      of congenital adrenal hyperplasia (CAH) resulted from mutations in the HSD3B2
      gene that impair steroidogenesis in both adrenals and gonads. We report clinical
      features and the results of HSD3B2 gene analysis of a Chinese pubertal girl with
      salt wasting 3betaHSD deficiency. METHOD: We retrospectively reviewed clinical
      presentations and steroid profiles of the patient diagnosed in Guangzhou Women
      and Children's Medical Center in 2013. PCR and direct sequencing were used to
      identify any mutation in the HSD3B2 gene. RESULT: A 13-year-old girl was
      diagnosed as CAH after birth because of salt-wasting with mild clitorimegaly and
      then was treated with glucocorticoid replacement. Breast and pubic hair
      development were normal, and menarche occurred at 12 yr, followed by menstrual
      bleeding about every 45 days. In the last one year laparoscopic operation and
      ovariocentesis were performed one after another for recurrent ovary cysts. Under
      corticoid acetate therapy, ACTH 17.10 pmol/L (normal 0-10.12), testosterone 1.31
      nmol/L (normal <0.7), dehydroepiandrosterone sulfate 13.30 umol/L (normal 0.95 -
      11.67), cortisol 720 nmol/L (normal 130-772.8), androstenedione, 17
      hydroxyprogesterone and progesterone were normal. Estradiol 461 pmol/L, follicle
      stimulating hormone 3.04 IU/L, luteinizing hormone 8.52 IU/L in follicular phase.
      A pelvic ultrasound showed lateral ovaries cysts (58 mm * 50 mm * 35 mm) and a
      midcycle-type endometrium. A novel nonsense mutation c.73G >T (p.E25X) was
      identified in HSD3B2 gene. The girl was homozygous and her mother was
      heterozygous, while her father was not identified with this mutation. CONCLUSION:
      A classic 3betaHSD deficiency is characterized by salt wasting and mild
      virilization in female. Ovary cysts may be the one of features of gonad phenotype
      indicating ovary 3betaHSD deficiency. A novel homozygous mutation c.73G
      >T(p.E25X) was related to the classical phenotype.

PMID- 25619356
TI  - [Measles pneumonitis in pediatric liver transplant recipients-case report].

PMID- 25619357
TI  - [Minute of congress of the sixth national pediatric clinical virology symposium].

PMID- 25619358
TI  - Nanomaterial-enabled stretchable conductors: strategies, materials and devices.
AB  - Stretchable electronics are attracting intensive attention due to their promising
      applications in many areas where electronic devices undergo large deformation
      and/or form intimate contact with curvilinear surfaces. On the other hand, a
      plethora of nanomaterials with outstanding properties have emerged over the past
      decades. The understanding of nanoscale phenomena, materials, and devices has
      progressed to a point where substantial strides in nanomaterial-enabled
      applications become realistic. This review summarizes recent advances in one such
      application, nanomaterial-enabled stretchable conductors (one of the most
      important components for stretchable electronics) and related stretchable devices
      (e.g., capacitive sensors, supercapacitors and electroactive polymer actuators),
      over the past five years. Focusing on bottom-up synthesized carbon nanomaterials
      (e.g., carbon nanotubes and graphene) and metal nanomaterials (e.g., metal
      nanowires and nanoparticles), this review provides fundamental insights into the
      strategies for developing nanomaterial-enabled highly conductive and stretchable
      conductors. Finally, some of the challenges and important directions in the area
      of nanomaterial-enabled stretchable conductors and devices are discussed. 

PMID- 25619359
TI  - Size and nanocrystallinity controlled gold nanocrystals: synthesis, electronic
      and mechanical properties.
AB  - The influence of nanocrystallinity on the electronic and mechanical properties of
      metal nanoparticles is still poorly understood, due to the difficulty in
      synthesizing nanoparticles with a controlled internal structure. Here, we report
      on a new method for the selective synthesis of Au nanoparticles in either a
      single-domain or a polycrystalline phase maintaining the same chemical
      environment. We obtain quasi-spherical nanoparticles whose diameter is tunable
      from 6 to 13 nm with a resolution down to ~0.5 nm and narrow size distribution (4
      5%). The availability of such high-quality samples allows the study of the impact
      of the particle size and nanocrystallinity on a number of parameters, such as
      plasmon dephasing time, electron-phonon coupling, period and damping time of the
      radial breathing modes. 

PMID- 25619360
TI  - Chronic red eye due to amelanotic conjuctival melanoma masquerading as pyogenic
      granuloma. More than meets the eye.

PMID- 25619361
TI  - Biodegradable protein nanocontainers.
AB  - The application of synthetic polymers for drug delivery often requires tremendous
      efforts to ensure biocompatibility and -degradation. To use the body's own
      substances can help to overcome these problems. Herein, we present the first
      synthesis of nanocontainers entirely composed of albumin proteins. These protein
      nanocontainers (PNCs) were loaded with hydrophilic compounds and release of the
      payload is triggered through natural lysis in vitro in human monocyte-derived
      dendritic cells (moDCs). No aggregation of PNCs in human blood plasma was
      observed, indicating stability for blood circulation. As the PNCs were readily
      taken up by moDCs, they are considered as a promising delivery platform for
      vaccination strategies and could minimize the risk of side effects caused by
      foreign carrier substances. 

PMID- 25619362
TI  - ULTRASONOGRAPHIC ELASTOGRAPHY OF THE LIVER, SPLEEN, KIDNEYS, AND PROSTATE IN
      CLINICALLY NOR-MAL BEAGLE DOGS [corrected].
AB  - Standard ultrasonography is often insensitive for distinguishing normal vs.
      diseased states for canine abdominal organs. Ultrasonographic elastography is a
      new technique that is becoming increasingly available and may help to improve
      sensitivity. This study evaluated the feasibility, repeatability, and
      reproducibility of strain elastography of the liver, spleen, kidneys, and
      prostate in healthy dogs and described the elasticity of each organ using strain
      values and strain ratios. The reproducibility of strain elastography was
      excellent, and intraobserver repeatability was moderate to excellent. The strain
      value of each organ was not significantly different among dogs (liver = 143.38 +/
      7.41, spleen = 141.04 +/- 9.03, left renal cortex = 141.26 +/- 7.50, right renal
      cortex = 145.80 +/- 7.79, and prostate = 135.46 +/- 5.80), except for the renal
      medulla (left = 51.19 +/- 4.54 and right = 51.93 +/- 5.09) (P < 0.05). The strain
      ratios for the liver, spleen, renal cortex, and prostate were similar with no
      significant difference (liver = 10.20 +/- 1.47, spleen = 8.40 +/- 1.53, left
      renal cortex = 9.62 +/- 1.56, right renal cortex = 8.29 +/- 1.63, and prostate =
      8.20 +/- 1.21), except for the renal medulla (left = 3.48 +/- 0.68 and right =
      2.95 +/- 0.63) (P < 0.05). Our results indicated that strain elastography was
      feasible for estimating tissue stiffness in the canine liver, spleen, kidneys,
      and prostate. This study provides basic information for strain values and strain
      ratios for the liver, spleen, kidneys, and prostate in clinically normal dogs. 

PMID- 25619364
TI  - Mourning in the psychoanalytic situation and in Shakespeare's The Tempest.
AB  - Recognizing that mourning builds psychic structure, the author highlights the
      ubiquitous and essential nature of mourning in the psychoanalytic situation.
      Reality testing is intimately connected to mourning and is the warp on which
      psychic structure is woven in the analytic situation. Reality testing necessarily
      involves opportunities for mourning and thus will be present in every analytic
      hour. The confrontation with reality is the basis for all processes of mourning,
      or for creating defenses against this painful experience. The author views
      mourning as fundamentally a transformational process, and Shakespeare's The
      Tempest is used to illustrate this aspect of mourning. 

PMID- 25619365
TI  - The texture of traumatic attachment: presence and ghostly absence in
      transgenerational transmission.
AB  - Work on the transgenerational transmission of trauma refers to unspoken stories
      across generations, but the actual mode of transmission has remained somewhat
      mysterious. Utilizing examples from her own life, the author illustrates how
      attachment patterns are a primary mode of transmission of trauma. When trauma
      revisits a person transgenerationally through dysregulated and disrupted
      attachment patterns, it is within the child's empathic attunement and search for
      a parental bond that the mode of transmission can be found. This will become the
      texture of traumatic attachment: how it feels to this child to feel connected to
      the parent. 

PMID- 25619363
TI  - Epigenetic changes in the CDKN2A locus are associated with differential
      expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell
      carcinoma.
AB  - Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC)
      is recognized as a distinct disease entity associated with improved survival. DNA
      hypermethylation profiles differ significantly by HPV status suggesting that a
      specific subset of methylated CpG loci could give mechanistic insight into HPV
      driven OPSCC. We analyzed genome-wide DNA methylation of primary tumor samples
      and adjacent normal mucosa from 46 OPSCC patients undergoing treatment at
      Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27
      beadchip. For each matched tissue set, we measured differentially methylated CpG
      loci using a change in methylation level (M value). From these analyses, we
      identified a 22 CpG loci panel for HPV+ OPSCC that included four CDKN2A loci
      downstream of the p16(INK4A) and p14(ARF) transcription start sites. This panel
      was significantly associated with overall HPV detection (P < 0.05; ROC area under
      the curve = 0.96, 95% CI: 0.91-1.0) similar to the subset of four CDKN2A-specific
      CpG loci (0.90, 95% CI: 0.82-0.99) with equivalence to the full 22 CpG panel. DNA
      hypermethylation correlated with a significant increase in alternative open
      reading frame (ARF) expression in HPV+ OPSCC primary tumors, but not to the other
      transcript variant encoded by the CDKN2A locus. Overall, this study provides
      evidence of epigenetic changes to the downstream region of the CDKN2A locus in
      HPV+ oropharyngeal cancer that are associated with changes in expression of the
      coded protein products.

PMID- 25619366
TI  - The elusiveness of masculinity: primordial vulnerability, lack, and the
      challenges of male development.
AB  - Reaching beyond the Oedipus prototype to address the unrepresentable
      vulnerability founded on the boy's infantile helplessness in contact with the
      mother's body, the author aims to identify the inherent tensions and enigmas of
      being male. He proposes that both the repudiation of femininity and the
      overvaluation of phallicity are unconsciously constructed to withstand the
      fundamental deficiency grounded in the asymmetry of the boy's prephallic relation
      with his primary object. This bodily based primordial vulnerability, marked by
      absence and lack, remains elusive-an unsymbolizable experience that provides the
      archaic matrix for adaptive and defensive phallicism, the oedipal complex, and
      genital progression. A clinical vignette is presented to illustrate these
      concepts. 

PMID- 25619367
TI  - Max Eitingon's rise and decline: the Berlin years.
AB  - Max Eitingon's main achievement was the foundation of the Berlin psychoanalytic
      Poliklinik that served both as an outpatient center and a training institute.
      Another area of his responsibility was the Verlag, the International
      Psychoanalytic Press. By 1926, he occupied several leading positions, including
      presidency of the International Psychoanalytical Association and editorship of
      the major psychoanalytic journal of the time. The basis of his power was his
      personal relationship with Freud, as well as his monetary wealth, which he put
      into the service of the Freudian cause. By 1932, he had suffered an overall
      setback, however, with the Berlin Institute losing its best teachers, the Verlag
      barely escaping bankruptcy, and the journal's editorship returning to Vienna. 

PMID- 25619368
TI  - O'Neill's journey.
AB  - This paper considers some of the processes through which Eugene O'Neill (1888
      1953) dramatically shaped his inner life and through which he created his plays.
      These processes at their finest are evident in his composition of Long Day's
      Journey into Night (1941a). During its 21-month composition, the play went
      through three different versions, as evidenced by the playwright's handwritten
      and typed materials (O'Neill, unpublished, a, b, c, d). This paper posits that
      each version reflects O'Neill's changing state of mind as he began to master his
      instinctual life, developing increasingly rich characters and creating a painful,
      deeply tragic vision. Thus, this paper shows that O'Neill's great artistic
      achievement reflected a great psychological one. 

PMID- 25619369
TI  - On the dream of convenience.

PMID- 25619370
TI  - Insight as defiance: a neglected aspect of self-awareness.

PMID- 25619371
TI  - Creativity and change in psychoanalysis: Jungian perspectives.

PMID- 25619372
TI  - Grief and reason: a response to Eric Kandel's Age of Insight.

PMID- 25619373
TI  - Working psychoanalytically with nonneurotic patients: theory and technique.

PMID- 25619381
TI  - Monensin, a small molecule ionophore, can be used to increase high mannose levels
      on monoclonal antibodies generated by Chinese hamster ovary production cell
      lines.
AB  - Asparagine-linked glycosylation of the constant region of monoclonal antibodies
      (mAbs) plays an important role in their stability and efficacy and is a critical
      product quality attribute that needs to be consistent between various process
      changes and production lots. Exact product quality match is also of the utmost
      importance for the development of biosimilar protein therapeutics. This poses a
      process development challenge since mAb glycosylation profiles can fluctuate
      easily with changes in process parameters. Therefore, there is a need to identify
      methods to modulate glycosylation levels on therapeutic antibodies during a
      production run in order to maintain consistent product quality profiles between
      different drug lots. Here, we demonstrate the use of a small molecule ionophore,
      monensin, to increase high mannose levels on multiple therapeutic human
      immunoglobulins (IgGs) in both plate-based small scale production models as well
      as in production bioreactors. This method is simple to implement and readily
      applicable for multiple production cell lines. Moreover, high mannose levels can
      be increased without significant negative impact on titer or cell culture
      performance. As such, monensin gives us a manipulable product quality lever.

PMID- 25619382
TI  - Increased risk of severe vaso-occlusive episodes after initial acute chest
      syndrome in children with sickle cell anemia less than 4 years old: Sleep and
      asthma cohort.
AB  - Previous studies have shown that the highest incidence of acute chest syndrome
      (ACS) in sickle cell disease occurs in children <4 years old, and a history of
      ACS at this age is a risk factor for future ACS episodes. However, the interval
      associated with the highest risk of subsequent ACS or severe pain is not known.
      Through this mixed retrospective-prospective observational study, the Sleep and
      Asthma Cohort, we sought to determine the interval after an initial ACS episode
      during which the majority of children <4 years old are rehospitalized for ACS or
      severe pain. The cumulative prevalence of rehospitalization for ACS or severe
      pain within 6 months, 1 years, and 2 years was calculated for children with an
      initial ACS episode <4 years old and compared to children with an initial ACS
      episode >=4 years old. A total of 44.8% and 55.2% of participants had an initial
      ACS episode <4 years and >=4 years old (Range: 4-17.7 years), respectively. At 1
      year following the initial ACS episode, children <4 years old had a significantly
      higher cumulative prevalence of rehospitalizations for ACS or pain as compared to
      children >=4 years of age, 62.5 and 39.1%, respectively (P = 0.009). After
      initial ACS episodes, the majority of children <4 years old will be
      rehospitalized for ACS or severe pain within one year, suggesting the need for a
      therapeutic intervention for this high-risk group.

PMID- 25619383
TI  - Gender-specific plasma proteomic biomarkers in patients with Anderson-Fabry
      disease.
AB  - AIMS: Anderson-Fabry disease (AFD) is an important X-linked metabolic disease
      resulting in progressive end-organ involvement, with cardiac disease being the
      dominant determinant of survival in a gender-dependent manner. Recent
      epidemiological screening for AFD suggests the prevalence is much higher than
      previously recognized, with estimates of 1:3000. Our aim was to discover novel
      plasma biomarker signatures in adult patients with AFD. METHODS AND RESULTS: We
      used an unbiased proteomic screening approach to discover novel plasma biomarker
      signatures. In the discovery cohort of 46 subjects, 14 healthy controls and 32
      patients with AFD, we used a mass spectrometry iTRAQ proteomic approach followed
      by multiple reaction monitoring (MRM) assays to identify biomarkers. Of the 38
      protein groups discovered by iTRAQ, 18 already had existing MRM assays. Based on
      MRM, we identified an eight-protein biomarker panel (22 kDa protein, afamin,
      alpha1 antichymotrypsin, apolipoprotein E, beta-Ala His dipeptidase, haemoglobin
      alpha-2, isoform 1 of sex hormone-binding globulin, and peroxiredoxin 2) that was
      very specific and sensitive for male AFD patients. In female AFD patients, we
      identified a nine-marker panel of proteins with only three proteins,
      apolipoprotein E, haemoglobin alpha-2, and peroxiredoxin 2, common to both
      genders, suggesting a gender-specific alteration in plasma biomarkers in patients
      with AFD. The biomarkers were validated in plasma samples from 48 subjects using
      MRM, and they performed inferiorly in patients with heart failure. CONCLUSIONS:
      We have identified gender-specific plasma protein biomarker panels that are
      specific and sensitive for the AFD phenotype. The gender-specific panels offer
      important insight into potential differences in pathophysiology and prognosis
      between males and females with AFD.

PMID- 25619384
TI  - PEG-imbedded PEO membrane developed by a novel highly efficient strategy toward
      superior gas transport performance.
AB  - Low-molecular-weight poly(ethylene glycol) (PEG) is deliberately incorporated
      into synthesized swellable poly(ethylene oxide) (PEO) membranes via a facile post
      treatment strategy. The membranes exhibit both larger fractional free volume
      (FFV) and a higher content of CO2-philic building units, resulting in significant
      increments in both CO2 permeability and CO2/H2 selectivity. The separation
      performance correlates nicely with the microstructure of the membranes. This
      study may provide useful insights in the formation and mass transport behavior of
      highly efficient polymeric membranes applicable to clean energy purification and
      CO2 capture, and possibly bridge the material-induced technology gap between
      academia and industry.

PMID- 25619385
TI  - Vertebrate spinal commissural neurons: a model system for studying axon guidance
      beyond the midline.
AB  - For bilaterally symmetric organisms, the transfer of information between the left
      and right side of the nervous system is mediated by commissures formed by neurons
      that project their axons across the body midline to the contralateral side of the
      central nervous system (CNS). After crossing the midline, many of these axons
      must travel long distances to reach their targets, including those that extend
      from spinal commissural neurons. Owing to the highly stereotyped trajectories of
      spinal commissural neurons that can be divided into several segments as these
      axons project to their targets, it is an ideal system for investigators to ask
      fundamental questions related to mechanisms of short- and long-range axon
      guidance, fasciculation, and choice point decisions at the midline intermediate
      target. In addition, studies of patterning genes of the nervous system have
      revealed complex transcription factor codes that function in a combinatorial
      fashion to specify individual classes of spinal neurons including commissural
      neurons. Despite these advances and the functional importance of spinal
      commissural neurons in mediating the transfer of external sensory information
      from the peripheral nervous system (PNS) to the CNS, only a handful of studies
      have begun to elucidate the mechanistic logic underlying their long-range
      pathfinding and the characterization of their synaptic targets. Using in vitro
      assays, in vivo labeling methodologies, in combination with both loss- and gain
      of-function experiments, several studies have revealed that the molecular
      mechanisms of long-range spinal commissural axon pathfinding involve an interplay
      between classical axon guidance cues, morphogens and cell adhesion molecules. For
      further resources related to this article, please visit the WIREs website.

PMID- 25619386
TI  - Co-targeting EGFR and Autophagy Impairs Ovarian Cancer Cell Survival during
      Detachment from the ECM.
AB  - Ovarian cancer (OC) remains the most aggressive and lethal gynecological tumor
      characterized by massive intraperitoneal dissemination and malignant ascites. The
      carcinoma cells exfoliated from the primary tumor and were further transformed in
      the ascites microenvironment. During this suspension process, multi-cellular
      spheroids are formed and these aggregates represent an invasive and
      chemoresistant cellular population fundamental to metastatic dissemination.
      Activation of EGFR signaling is involved in increased cell metastasis and
      decreased apoptosis of ovarian cancer. The application of EGFR Inhibition in
      ovarian cancer was hampered for its limited benefit as a solitary therapy. In
      this work, our results primarily indicated that autophagy was induced in response
      to EGFR specific inhibitor AG1478 in OC cell lines generated spheres and ascites
      primary spheroids, characterized by the elevation of LC3-II, Beclin1 and Atg5.
      Blockage of autophagy with 3MA notably promoted spheroid death in suspension as
      well as AG1478-induced cell apoptosis, suggesting a protective autophagy
      contribution during tumor cells in suspension or under EGFR inhibition.
      Consequently, inhibiting autophagy with 3MA significantly enhanced the inhibitory
      effect of AG1478 on tumor cell peritoneal propagation in SKOV3 i.p. xenografts
      model. In addition, elevated EGFR, Beclin1, and Atg5 mRNA levels were associated
      with decreased ovarian cancer patient survival. Together, our findings suggested
      that targeting autophagy held the potential to improve EGFR inhibition benefit in
      the treatment of ovarian cancer cells during detachment from the extra-cellular
      matrix (ECM), and that this combination strategy might provide a new treatment
      option in controlling peritoneal metastasis of ovarian cancer. 

PMID- 25619387
TI  - Involvement of mesenchymal stem cells in cancer progression and metastases.
AB  - Mesenchymal stem/stromal cells (MSCs) are known to be the helpers for the healing
      of tissue damage, often referred to as ambulatory cells. However, MSCs are also
      recruited by cancer cells to similarly aid in tumor growth and progression. In
      this review, some of the key steps in cancer progression and metastases are
      described including the various steps in which MSCs participate and may play
      important roles. MSCs aid in cancer cells' ability to evade immune attack, while
      promoting tumor angiogenesis, even being counter-acting against chemotherapeutics
      and other drugs used to fight various cancers. Furthermore, MSCs participate in
      many of the crucial steps in invasion and metastasis, including stimulating the
      epithelial-mesenchymal transition (EMT) and induction of stem-like properties
      that allow cancer stem cells to increase their survivability through the
      circulation. These steps are described in detail. Differences between circulating
      tumor cells (CTCs) and cancer stem cells (CSCs) are discussed, along with
      descriptions of the formation of a pre-metastatic niche, the role of exosomes
      from both cancer cells and MSCs in metastasis and tumor reseeding (self-seeding).
      More and more, MSCs are being proposed as a promising tumor targeting drug
      delivery tool. In order to fulfill this promise, further understanding of the
      precise roles that MSCs play in the process of cancer metastases must be
      achieved, in attempting to create remedies that will improve the outcome of
      available therapeutics. 

PMID- 25619388
TI  - gamma-Oryzanol reduces caveolin-1 and PCGEM1 expression, markers of
      aggressiveness in prostate cancer cell lines.
AB  - BACKGROUND: Prostate cancer is a leading cause of death among men due to the
      limited number of treatment strategies available for advanced disease. gamma
      oryzanol is a component of rice bran, rich in phytosterols, known for its
      antioxidant, anti-carcinogenic and endocrinological effects. It is known that
      gamma-oryzanol may affect prostate cancer cells through the down regulation of
      the antioxidant genes and that phytosterols have anti-proliferative and apoptotic
      effects. There are evidences showing that some of the components of gamma
      oryzanol can modulate genes involved in the development and progression of
      prostate cancer, as caveolin-1 (Cav-1) and prostate specific androgen-regulated
      gene (PCGEM1). METHODS: To determine the effects of gamma-oryzanol on prostate
      cancer cell survival we evaluated the cell viability and biomass by MTT and
      sulforhodamine B assays, respectively. Cell death, cell cycle and pERK1/2
      activity were assessed by flow cytometry. The changes in gene expression involved
      in the survival and progression of prostate cancer cav-1 and PCGEM1 genes were
      evaluated by quantitative real time reverse transcriptase polymerase chain
      reaction (RT-PCR) and cav-1 protein by immunofluorescence followed by confocal
      microscopy analysis. RESULTS: We found that gamma-oryzanol decreases cell
      viability and culture biomass by apoptosis and/or necrosis death in androgen
      unresponsive (PC3 and DU145) and responsive (LNCaP) cell lines, and signals
      through pERK1/2 in LNCaP and DU145 cells. gamma-oryzanol also appears to block
      cell cycle progression at the G2/M in PC3 and LNCaP cells and at G0/G1 in DU145
      cells. These effects were accompanied by a down regulation in the expression of
      the cav-1 in both androgen unresponsive cell lines and PCGEM1 gene in DU145 and
      LNCaP cells. CONCLUSION: In summary, we used biochemical and genetics approaches
      to demonstrate that gamma-oryzanol show a promising adjuvant role in the
      treatment of prostate cancer.

PMID- 25619389
TI  - Piperlongumine induces apoptotic and autophagic death of the primary myeloid
      leukemia cells from patients via activation of ROS-p38/JNK pathways.
AB  - AIM: To investigate the effects of piperlongumine (PL), an anticancer alkaloid
      from long pepper plants, on the primary myeloid leukemia cells from patients and
      the mechanisms of action. METHODS: Human BM samples were obtained from 9 patients
      with acute or chronic myeloid leukemias and 2 patients with myelodysplastic
      syndrome (MDS). Bone marrow mononuclear cells (BMMNCs) were isolated and
      cultured. Cell viability was determined using MTT assay, and apoptosis was
      examined with PI staining or flow cytometry. ROS levels in the cells were
      determined using DCFH-DA staining and flow cytometry. Expression of apoptotic and
      autophagic signaling proteins was analyzed using Western blotting. RESULTS: PL
      inhibited the viability of BMMNCs from the patients with myeloid leukemias (with
      IC50 less than 20 MUmol/L), but not that of BMMNCs from a patient with MDS.
      Furthermore, PL (10 and 20 MUmol/L) induced apoptosis of BMMNCs from the patients
      with myeloid leukemias in a dose-dependent manner. PL markedly increased ROS
      levels in BMMNCs from the patients with myeloid leukemias, whereas pretreatment
      with the antioxidant N-acetyl-L-cysteine abolished PL-induced ROS accumulation
      and effectively reduced PL-induced cytotoxicity. Moreover, PL markedly increased
      the expression of the apoptotic proteins (Bax, Bcl-2 and caspase-3) and
      autophagic proteins (Beclin-1 and LC3B), and phosphorylation of p38 and JNK in
      BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the
      specific p38 inhibitor SB203580 or the specific JNK inhibitor SP600125 partially
      reversed PL-induced ROS production, apoptotic/autophagic signaling activation and
      cytotoxicity. CONCLUSION: Piperlongumine induces apoptotic and autophagic death
      of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK
      pathways.

PMID- 25619390
TI  - Matrine pretreatment improves cardiac function in rats with diabetic
      cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.
AB  - AIM: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a
      variety of pharmacological activities and potential therapeutic value in
      cardiovascular diseases. In this study we examined the protective effects of
      matrine against diabetic cardiomyopathy (DCM) in rats. METHODS: Male SD rats were
      injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was
      pretreated with matrine (200 mg.kg(-1).d(-1), po) for 10 consecutive days before
      STZ injection. Left ventricular function was evaluated using invasive hemodynamic
      examination, and myocardiac apoptosis was assessed. Primary rat myocytes were
      used for in vitro experiments. Intracellular ROS generation, MDA content and GPx
      activity were determined. Real-time PCR and Western blotting were performed to
      detect the expression of relevant mRNAs and proteins. RESULTS: DCM rats exhibited
      abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ
      injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM
      rats showed markedly increased apoptosis, excessive ROS production, and
      activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with
      matrine significantly decreased non-fasting blood glucose levels and improved LV
      function in DCM rats, which were associated with reducing apoptosis and ROS
      production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac
      tissues. Incubation in a high-glucose medium induced oxidative stress and
      activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were
      significantly attenuated by pretreatment with N-acetylcysteine. CONCLUSION:
      Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting
      in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac
      function via suppressing ROS/TLR-4 signaling pathway.

PMID- 25619391
TI  - Liraglutide reduces the body weight and waist circumference in Chinese overweight
      and obese type 2 diabetic patients.
AB  - AIM: To investigate the effects of liraglutide, a glucagon-like peptide-1 (GLP-1)
      receptor activator, on body weight and waist circumference in Chinese overweight
      and obese type 2 diabetic patients. METHODS: A total of 328 Chinese overweight
      and obese type 2 diabetic patients were included in this multi-center, open
      labeled and self-controlled clinical study. The patients were subcutaneously
      injected with liraglutide once daily for 24 weeks as add-on therapy to their
      previous hypoglycemic treatments. Statistical analyses were performed using SPSS
      software package version 11.5 for Windows. RESULTS: Liraglutide treatment caused
      significant reduction of the mean body weight (from 86.61+/-14.09 to 79.10+/
      13.55 kg) and waist circumference (from 101.81+/-13.96 to 94.29+/-14.17 cm),
      resulting in body weight lose of 5%-10% in 43.67% patients, and body weight loss
      above 10% in 34.06% patients, who had significant lower plasma creatinine levels.
      Baseline waist circumference, BMI and HOMA-IR were independently correlated with
      the body weight loss. Furthermore, liraglutide treatment significantly decreased
      HbA1c levels (from 8.66%+/-2.17% to 6.92%+/-0.95%) with HbA1c<7.0% in 35.37%
      patients, who had a significantly lower baseline level of HbA1c, but higher
      baseline levels of C peptide and glucagon. Moreover, liraglutide treatment
      resulted in greater body weight loss in patients with a long duration of
      diabetes, and better glycemic control in patients with a short duration of
      diabetes. CONCLUSION: Liraglutide significantly reduces body weight and waist
      circumference in Chinese overweight and obese type 2 diabetic patients. Patients
      with apparent visceral obesity, insulin resistance and a long duration of
      diabetes may have greater body weight loss; whereas patients with high insulin
      secreting ability, hyperglucagonemia, and short-duration diabetes may obtain
      better glycemic control with liraglutide.

PMID- 25619392
TI  - Resveratrol induces apoptosis of human chronic myelogenous leukemia cells in
      vitro through p38 and JNK-regulated H2AX phosphorylation.
AB  - AIM: The phosphorylation of histone H2AX, a novel tumor suppressor protein, is
      involved in regulation of cancer cell apoptosis. The aim of this study was to
      examine whether H2AX phosphorylation was required for resveratrol-induced
      apoptosis of human chronic myelogenous leukemia (CML) cells in vitro. METHODS:
      K562 cells were tested. Cell apoptosis was analyzed using flow cytometry, and the
      phosphorylation of H2AX and other signaling proteins was examined with Western
      blotting. To analyze the signaling pathways, the cells were transfected with
      lentiviral vectors encoding H2AX-wt or specific siRNAs. RESULTS: Treatment of
      K562 cells with resveratrol (20-100 MUmol/L) induced apoptosis and
      phosphorylation of H2AX at Ser139 in time- and dose-dependent manners, but
      reduced phosphorylation of histone H3 at Ser10. Resveratrol treatment activated
      two MAPK family members p38 and JNK, and blocked the activation of another MAPK
      family member ERK. Pretreatment with the p38 inhibitor SB202190 or the JNK
      inhibitor SP600125 dose-dependently reduced resveratrol-induced phosphorylation
      of H2AX, which were also observed when the cells were transfected with p38- or
      JNK-specific siRNAs. Overexpression of H2AX in K562 cells markedly increased
      resveratrol-induced apoptosis, whereas overexpression of H2AX-139m (Ser139 was
      mutated to block phosphorylation) inhibited resveratrol-induced apoptosis. K562
      cells transfected with H2AX-specific siRNAs were resistant to resveratrol-induced
      apoptosis. CONCLUSION: H2AX phosphorylation at Ser139 in human CML cells, which
      is regulated by p38 and JNK, is essential for resveratrol-induced apoptosis.

PMID- 25619393
TI  - Bigelovin inhibits STAT3 signaling by inactivating JAK2 and induces apoptosis in
      human cancer cells.
AB  - AIM: To study the function and mechanism of bigelovin, a sesquiterpene lactone
      from the flower of Chinese herb Inula hupehensis, in regulating JAK2/STAT3
      signaling and cancer cell growth. METHODS: HepG2 cells stably transfected with
      the STAT3-responsive firefly luciferase reporter plasmid (HepG2/STAT3 cells), and
      a panel of human cancer cell lines were used to identify active compounds. Cell
      viability was measured using MTT assay. Western blotting was used to detect
      protein expression and phosphorylation. Kinase assays were performed and the
      reaction between bigelovin and thiol-containing compounds was analyzed with LC
      MS. RESULTS: Bigelovin (1-50 MUmol/L) dose-dependently inhibited the IL-6-induced
      STAT3 activation in HepG2/STAT3 cells (IC50=3.37 MUmol/L) and the constitutive
      STAT3 activation in A549 and MDA-MB-468 cells. Furthermore, bigelovin dose
      dependently inhibited JAK2 phosphorylation in HeLa and MDA-MB-468 cells, as well
      as the enzymatic activity of JAK2 in vitro (IC50=44.24 MUmol/L). Pretreatment of
      the cells with DTT (500 MUmol/L) or GSH (500 MUmol/L) eliminated the inhibitory
      effects of bigelovin on the IL-6-induced and the constitutive STAT3 activation.
      The results in LC-MS analysis suggested that bigelovin might react with cysteine
      residues of JAK2 leading to inactivation of JAK2. Bigelovin (5 and 20 MUmol/L)
      had no effects on the signaling pathways of growth factors EGF, PDGF or insulin.
      Finally, bigelovin suppressed the cell viability and induced apoptosis in 10
      different human cancer cell lines, particularly those with constitutively
      activated STAT3. CONCLUSION: Bigelovin potently inhibits STAT3 signaling by
      inactivating JAK2, and induces apoptosis of a variety of human cancer cells in
      vitro.

PMID- 25619394
TI  - Modulation of the pentose phosphate pathway alters phase I metabolism of
      testosterone and dextromethorphan in HepG2 cells.
AB  - AIM: The pentose phosphate pathway (PPP) is involved in the activity of glucose-6
      phosphate dehydrogenase (G6PD) and generation of NADPH, which plays a key role in
      drug metabolism. The aim of this study was to investigate the effects of
      modulation of the PPP on drug metabolism capacity in vitro. METHODS: A pair of
      hepatic cell lines, ie, the cancerous HepG2 cells and normal L02 cells, was used.
      The expression of CYP450 enzymes, p53 and G6PD in the cells were analyzed. The
      metabolism of testosterone (TEST, 10 MUmol/L) and dextromethorphan (DEM, 1
      MUmol/L), the two typical substrates for CYP3A4 and CYP2D6, in the cells was
      examined in the presence of different agents. RESULTS: Both the expression and
      metabolic activities of CYP3A4 and CYP2D6 were considerably higher in HepG2 cells
      than in L02 cells. The metabolism of TEST and DEM in HepG2 cells was dose
      dependently inhibited by the specific CYP3A4 inhibitor ketoconazole and CYP2D6
      inhibitor quinidine. Addition of the p53 inhibitor cyclic PFT-alpha (5, 25
      MUmol/L) in HepG2 cells dose-dependently enhanced the metabolism of DEM and TEST,
      whereas addition of the p53 activator NSC 66811 (3, 10, 25 MUmol/L) dose
      dependently inhibited the metabolism. Furthermore, addition of the G6PD inhibitor
      6-aminonicotinamide (5, 15 MUmol/L) in HepG2 cells dose-dependently inhibited the
      metabolism of DEM and TEST, whereas addition of the PPP activity stimulator
      menadione (1, 5, 15 MUmol/L) dose-dependently enhanced the metabolism.
      CONCLUSION: Modulation of p53 and the PPP alters the metabolism of DEM and TEST,
      suggesting that the metabolic flux pattern of PPP may be closely involved in drug
      metabolism and the individual variance.

PMID- 25619395
TI  - The PPARgamma agonist, rosiglitazone, attenuates airway inflammation and
      remodeling via heme oxygenase-1 in murine model of asthma.
AB  - AIM: Rosiglitazone is one of the specific PPARgamma agonists showing potential
      therapeutic effects in asthma. Though PPARgamma activation was considered
      protective in inhibiting airway inflammation and remodeling in asthma, the
      specific mechanisms are still unclear. This study was aimed to investigate
      whether heme oxygenase-1 (HO-1) related pathways were involved in rosiglitazone
      activated PPARgamma signaling in asthma treatment. METHODS: Asthma was induced in
      mice by multiple exposures to ovalbumin (OVA) in 8 weeks. Prior to every OVA
      challenge, the mice received rosiglitazone (5 mg/kg, p.o.). After the mice were
      sacrificed, the bronchoalveolar lavage fluid (BALF), blood samples and lungs were
      collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue
      were assessed, and the expression of PPARgamma, HO-1 and p21 proteins was also
      examined. RESULTS: Rosiglitazone administration significantly attenuated airway
      inflammation and remodeling in mice with OVA-induced asthma, which were evidenced
      by decreased counts of total cells, eosinophils and neutrophils, and decreased
      levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer
      thickness and reduced airway collagen deposition. Furthermore, rosiglitazone
      administration significantly increased PPARgamma, HO-1 and p21 expression and HO
      1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the
      therapeutic effects of rosiglitazone were significantly impaired by co
      administration of the HO-1 inhibitor ZnPP. CONCLUSION: Rosiglitazone effectively
      attenuates airway inflammation and remodeling in OVA-induced asthma of mice by
      activating PPARgamma/HO-1 signaling pathway.

PMID- 25619396
TI  - Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat
      experimental membranous nephropathy.
AB  - AIM: SM934 is a novel water-soluble artemisinin derivative with immunoregulatory
      activities that has been used to treat murine lupus nephritis. In the current
      study, we investigated the effects of SM934 on rat experimental membranous
      nephropathy. METHODS: Passive Heymann nephritis (PHN) was induced in SD rats by
      intraperitoneal injection of anti-Fx1A serum. The rats were orally administered
      SM934 (12.5 and 25 mg.kg(-1).d(-1)) or prednisolone (5 mg.kg(-1).d(-1)) for 28 d.
      Blood and urine sample, and kidney tissue were collected for analyses. Human
      complement C3a-induced injury of HK-2 cells was used for in vitro experiments.
      RESULTS: Treatment of PHN rats with SM934 or prednisolone attenuated the
      progression of glomerulonephritis and renal fibrosis, as evidenced by the reduced
      level of proteinuria and circulating antibodies, as well as by the reduced immune
      complex deposition, reversed podocyte injuries, and attenuated tubulointerstitial
      fibrosis in the kidneys. Furthermore, the two drugs suppressed TGF-beta1
      expression and Smad2/3 phosphorylation, and increased Smad7 expression in the
      kidneys. The two doses of SM934 produced almost identical therapeutic effects on
      PHN rats. Pretreatment with SM934 or a C3a receptor antagonist blocked the C3a
      induced epithelial-mesenchymal transition in HK-2 cells in vitro. CONCLUSION:
      SM934 ameliorates kidney injury and attenuates the tubulointerstitial fibrosis in
      PHN rats by down-regulation of the TGF-beta1/Smad signaling pathway.

PMID- 25619397
TI  - Galectin isolated from parasite inhibits remission of experimental autoimmune
      encephalomyelitis by up-regulating autoantibody.
AB  - Recently, parasite infections or parasite-derived products have been suggested as
      a therapeutic strategy with suppression of immunopathology, which involves the
      induction of regulatory T cells or/and T helper type 2 (Th2) responses. In a
      recent study, researchers reported that constructed recombinant galectin (rTl
      gal) isolated from an adult worm of the gastrointestinal nematode parasite
      Toxascaris leonina attenuated clinical symptoms of inflammatory bowel disease in
      mice treated with dextran sulphate sodium. Noting the role of rTl-gal in
      inflammatory disease, we attempted to investigate the effect of the parasite via
      its rTl-gal on neuronal autoimmune disease using experimental autoimmune
      encephalomyelitis (EAE), a mouse inflammatory and demyelinating autoimmune
      disease model of human multiple sclerosis. In this model, rTl-gal-treated
      experimental autoimmune encephalomyelitis (EAE) mice failed to recover after the
      peak of the disease, leading to persistent central nervous system (CNS) damage,
      such as demyelination, gliosis and axonal damage. Further, rTl-gal-treated EAE
      mice markedly increased the number of CD45R/B220(+) B cells in both infiltrated
      inflammation and the periphery, along with the increased production of
      autoantibody [anti-myelin oligodendrocyte glycoprotein (MOG)35-55 ] in serum at
      chronic stage. Upon antigen restimulation, rTl-gal treatment affected the release
      of overall cytokines, especially interferon (IFN)-gamma and tumour necrosis
      factor (TNF)-alpha. Our results suggest that galectin isolated from a
      gastrointestinal parasite can deliver a harmful effect to EAE contrary to its
      beneficial effect on inflammatory bowel disease. 

PMID- 25619399
TI  - Sox2 is the faithful marker for pluripotency in pig: evidence from embryonic
      studies.
AB  - BACKGROUND: Mammalian first lineage segregation generates trophectoderm (TE) and
      pluripotent inner cell mass (ICM), which provides an ideal model for studying the
      mechanisms of maintenance and loss of pluripotency. In mouse, the transcription
      factor OCT4 restricts to ICM and plays a key role in TE/ICM specification and
      pluripotent regulatory networks. However, in pig, OCT4 does not restrict to ICM
      cells, suggesting a different molecular basis in TE/ICM specification and
      pluripotent regulatory networks. RESULTS: To explore molecular basis of porcine
      TE/ICM specification and pluripotent regulatory networks, we examined expression
      pattern of pluripotency factors, including SOX2, REX1, SALL4, ESG1, NANOG, TBX3,
      LIN28, KLF2, and KLF5, in porcine blastocysts. We found that SOX2 is a faithful
      pluripotent marker that anchored to the pluripotent cells including embryonic
      part cells, ICM cells and newly EPI cells along with developmental progress,
      whereas OCT4 expressed in almost all the cells at the same time. Consistently,
      analysis of spatiotemporal distribution of SOX2 and the TE marker CDX2 revealed
      an exclusive expression pattern in D6 blastocysts, whereas no correlation was
      observed between OCT4 and CDX2 at the same stage. CONCLUSIONS: Our results
      provide a molecular basis in porcine embryonic patterning and a clue for further
      studying porcine pluripotent regulatory networks.

PMID- 25619398
TI  - Observational infant exploratory [(14)C]-paracetamol pharmacokinetic
      microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.
AB  - AIMS: The aims of the study were to compare [(14)C]-paracetamol ([(14)C]-PARA)
      paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose
      or an isolated microdose and to develop further and validate accelerator mass
      spectrometry (AMS) bioanalysis in the 0-2 year old age group. METHODS: [(14)C]
      PARA concentrations in 10-15 ul plasma samples were measured after enteral or
      i.v. administration of a single [(14)C]-PARA microdose or mixed in with
      therapeutic dose in infants receiving PARA as part of their therapeutic regimen.
      RESULTS: Thirty-four infants were included in the PARA PK analysis for this
      study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6)
      and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in
      parentheses) for these dosed groups were 1.46 (1.00) l h(-1), 1.76 (1.07) l h(
      1), 2.93 (2.08) l h(-1) and 2.72 (3.10) l h(-1), t(1/2) values 2.65 h, 2.55 h,
      8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l(-1) h) values were 0.90
      (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). CONCLUSIONS: All necessary
      ethical, scientific, clinical and regulatory procedures were put in place to
      conduct PK studies using enteral and systemic microdosing in two European
      centres. The pharmacokinetics of a therapeutic dose (mg kg(-1)) and a microdose
      (ng kg(-1)) in babies between 35 to 127 weeks post-menstrual age. [(14)C]-PARA
      pharmacokinetic parameters were within a two-fold range after a therapeutic dose
      or a microdose. Exploratory studies using doses significantly less than
      therapeutic doses may offer ethical and safety advantages with increased
      bionalytical sensitivity in selected exploratory paediatric pharmacokinetic
      studies.

PMID- 25619400
TI  - Early development of the neural plate: new roles for apoptosis and for one of its
      main effectors caspase-3.
AB  - Despite its tremendous complexity, the vertebrate nervous system emerges from a
      homogenous layer of neuroepithelial cells, the neural plate. Its formation relies
      on the time- and space-controlled progression of developmental programs.
      Apoptosis is a biological process that removes superfluous and potentially
      dangerous cells and is implemented through the activation of a molecular pathway
      conserved during evolution. Apoptosis and an unconventional function of one of
      its main effectors, caspase-3, contribute to the patterning and growth of the
      neuroepithelium. Little is known about the intrinsic and extrinsic cues
      controlling activities of the apoptotic machinery during development. The BarH
      like (Barhl) proteins are homeodomain-containing transcription factors. The
      observations in Caenorhabditis elegans, Xenopus, and mice document that Barhl
      proteins act in cell survival and as cell type-specific regulators of a caspase-3
      function that limits neural progenitor proliferation. In this review, we discuss
      the roles and regulatory modes of the apoptotic machinery in the development of
      the neural plate. We focus on the Barhl2, the Sonic Hedgehog, and the Wnt
      pathways and their activities in neural progenitor survival and proliferation.

PMID- 25619401
TI  - Revisiting the origin and diversification of vascular plants through a
      comprehensive Bayesian analysis of the fossil record.
AB  - Plants have a long evolutionary history, during which mass extinction events
      dramatically affected Earth's ecosystems and its biodiversity. The fossil record
      can shed light on the diversification dynamics of plant life and reveal how
      changes in the origination-extinction balance have contributed to shaping the
      current flora. We use a novel Bayesian approach to estimate origination and
      extinction rates in plants throughout their history. We focus on the effect of
      the 'Big Five' mass extinctions and on estimating the timing of origin of
      vascular plants, seed plants and angiosperms. Our analyses show that plant
      diversification is characterized by several shifts in origination and extinction
      rates, often matching the most important geological boundaries. The estimated
      origin of major plant clades predates the oldest macrofossils when considering
      the uncertainties associated with the fossil record and the preservation process.
      Our findings show that the commonly recognized mass extinctions have affected
      each plant group differently and that phases of high extinction often coincided
      with major floral turnovers. For instance, after the Cretaceous-Paleogene
      boundary we infer negligible shifts in diversification of nonflowering seed
      plants, but find significantly decreased extinction in spore-bearing plants and
      increased origination rates in angiosperms, contributing to their current
      ecological and evolutionary dominance. 

PMID- 25619403
TI  - Dusky damselfish Stegastes fuscus relational learning: evidences from associative
      and spatial tasks.
AB  - This study investigated the ability of the dusky damselfish Stegastes fuscus to
      associate conditioned and unconditioned stimuli (single CS-US) and to find a
      specific place in a clueless ambiece (spatial learning). After tested for colour
      preference and showing no specific colour attractively, the fish were trained to
      associate a colour cue with a stimulus fish (conspecific). Fish were then
      challenged to locate the exact place where the stimulus fish was presented.
      Stegastes fuscus spent most time close to the zone where stimulus was presented,
      even without obvious marks for orientation. The results confirm that S. fuscus
      show single CS-US learning and suggest the fish ability for spatial orientation.
      Stegastes fuscus appears to use multiple senses (sight and lateral line) for cues
      association and recall, and appear to perform relational learning similar to
      mammals. These data suggest the importance of cognitive skill for reef fishes
      that may have contributed to their establishment and evolutionary success in such
      complex environment.

PMID- 25619402
TI  - Modification of endoscopic medial maxillectomy: a novel approach for inverted
      papilloma of the maxillary sinus.
AB  - OBJECTIVE: To describe modification to endoscopic medial maxillectomy for
      treating extensive Krouse stage II or III inverted papilloma of the nasal and
      maxillary sinus. METHOD: Ten patients with inverted papilloma arising from the
      nasoantral area underwent diagnostic nasal endoscopy, contrast-enhanced computed
      tomography scanning of the paranasal sinus and pre-operative biopsy of the nasal
      mass. They were all managed using endoscopic medial maxillectomy and followed up
      for seven months to three years without recurrence. RESULTS: Most patients were
      aged 41-60 years at presentation, and most were male. Presenting symptoms were
      nasal obstruction, mass in the nasal cavity and epistaxis. In each case, computed
      tomography imaging showed a mass involving the nasal cavity and maxillary sinus,
      with bony remodelling. The endoscopic medial maxillectomy approach was modified
      by making an incision in the pyriform aperture and removing part of the
      anterolateral wall of the maxilla bone en bloc. CONCLUSION: Modified endoscopic
      medial maxillectomy providing full access to the maxillary and ethmoid sinuses is
      described in detail. This effective, reproducible technique is associated with
      reduced operative time and morbidity.

PMID- 25619404
TI  - Reconstructed metagenomes reveal changes of microbial functional profiling during
      PAHs degradation along a rice (Oryza sativa) rhizosphere gradient.
AB  - AIMS: The response of microbial metagenome to polycyclic aromatic hydrocarbons
      (PAHs) degradation in the rice rhizosphere remains poorly understood. We
      investigated the spatial and temporal variations of microbial communities and
      reconstructed metagenomes along the rice rhizosphere gradient during PAHs
      degradation. METHODS AND RESULTS: The experiment was performed in rhizoboxes, in
      which the rhizosphere region was divided into five 1-mm thick layers. Based on
      denaturant gradient gel electrophoresis profiling and sequencing of bacterial and
      archaeal 16S rRNA genes, predicted metagenomes were reconstructed. The microbial
      communities in the rice rhizosphere were influenced by the PAHs concentration and
      distance from the root surface during PAHs degradation. Correlation network
      analysis showed that archaea played an important role in PAHs degradation.
      Predicted metagenomes can be clustered into two groups with high and low PAHs
      degrading potential, respectively. The relative abundance of genes for defense
      mechanisms, replication, recombination and reparation was significantly higher in
      samples with high PAHs degrading potentials. The relative abundance of the
      dioxygenase gene was greater near the root surface of the rice. However, the
      abundance of aldolase and dehydrogenase was constant in rhizosphere soils at
      different distances from the root surface. CONCLUSIONS: Distance from root
      surface and PAH concentrations affected the microbial communities and metagenomes
      in rice rhizosphere. The abundance of dioxygenase genes relating to PAH
      degradation in metagenomes mirrored the PAH degradation potential in rice
      rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings suggested that
      the predicted metagenomes reconstructed from 16S rRNA marker gene sequences
      provide further insights into the spatial variation and dynamics of microbial
      functioning that occur during bioremediation.

PMID- 25619405
TI  - The Arabidopsis ceramidase AtACER functions in disease resistance and salt
      tolerance.
AB  - Ceramidases hydrolyze ceramide into sphingosine and fatty acids. In mammals,
      ceramidases function as key regulators of sphingolipid homeostasis, but little is
      known about their roles in plants. Here we characterize the Arabidopsis
      ceramidase AtACER, a homolog of human alkaline ceramidases. The acer-1 T-DNA
      insertion mutant has pleiotropic phenotypes, including reduction of leaf size,
      dwarfing and an irregular wax layer, compared with wild-type plants. Quantitative
      sphingolipid profiling showed that acer-1 mutants and the artificial microRNA
      mediated silenced line amiR-ACER-1 have high ceramide levels and decreased long
      chain bases. AtACER localizes predominantly to the endoplasmic reticulum, and
      partially to the Golgi complex. Furthermore, we found that acer-1 mutants and
      AtACER RNAi lines showed increased sensitivity to salt stress, and lines
      overexpressing AtACER showed increased tolerance to salt stress. Reduction of
      AtACER also increased plant susceptibility to Pseudomonas syringae. Our data
      highlight the key biological functions of ceramidases in biotic and abiotic
      stresses in plants. 

PMID- 25619406
TI  - Assessing the utility of whole genome amplified DNA for next-generation molecular
      ecology.
AB  - DNA quantity can be a hindrance in ecological and evolutionary research
      programmes due to a range of factors including endangered status of target
      organisms, available tissue type, and the impact of field conditions on
      preservation methods. A potential solution to low-quantity DNA lies in whole
      genome amplification (WGA) techniques that can substantially increase DNA yield.
      To date, few studies have rigorously examined sequence bias that might result
      from WGA and next-generation sequencing of nonmodel taxa. To address this
      knowledge deficit, we use multiple displacement amplification (MDA) and double
      digest RAD sequencing on the grey mouse lemur (Microcebus murinus) to quantify
      bias in genome coverage and SNP calls when compared to raw genomic DNA (gDNA). We
      focus our efforts in providing baseline estimates of potential bias by following
      manufacturer's recommendations for starting DNA quantities (>100 ng). Our results
      are strongly suggestive that MDA enrichment does not introduce systematic bias to
      genome characterization. SNP calling between samples when genotyping both de-novo
      and with a reference genome are highly congruent (>98%) when specifying a minimum
      threshold of 20X stack depth to call genotypes. Relative genome coverage is also
      similar between MDA and gDNA, and allelic dropout is not observed. SNP
      concordance varies based on coverage threshold, with 95% concordance reached at
      ~12X coverage genotyping de-novo and ~7X coverage genotyping with the reference
      genome. These results suggest that MDA may be a suitable solution for next
      generation molecular ecological studies when DNA quantity would otherwise be a
      limiting factor. 

PMID- 25619407
TI  - Standards of practice for the adult mental health workforce: meeting the needs of
      families where a parent has a mental illness.
AB  - This article outlines the development of practice standards for the adult mental
      health workforce for addressing the needs of families where a parent has a mental
      illness (FaPMI). The practice standards recommended here were formulated using a
      modified cooperative inquiry process with a group of senior clinical leaders in
      adult mental health services in Australia, following consultation with the
      available literature and policy documents. The aim of the project was to
      generate, align, and operationalize family-inclusive practice standards within
      the core activities of the adult mental health workforce and integrate into the
      continuum of care and recovery for service users who are parents of dependent
      children. As part of a modified Delphi method, the standards were also ranked by
      the senior clinical leaders to determine what they believe to be essential and
      recommended practices for the adult mental health workforce they manage. We argue
      that developing practice standards that provide practical and realistic
      expectations of the adult mental health service workforce enable services and
      workers to better adapt practice to respond to FaPMI. 

PMID- 25619409
TI  - Chondroid hamartoma of the lung presenting as cavern.

PMID- 25619410
TI  - Safety, tolerability, and efficacy of azilsartan medoxomil with or without
      chlorthalidone during and after 8 months of treatment for hypertension.
AB  - A phase 3, 26-week, open-label, titrate-to-target study (n=418) assessed the
      safety of azilsartan medoxomil (AZL-M) alone and with chlorthalidone (CLD),
      followed by a 6-week, double-blind, placebo-controlled reversal phase with change
      in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood
      pressure (BP) was <140/90 mm Hg (<130/80 mm Hg with diabetes/chronic kidney
      disease). AZL-M was initiated at 40 mg once a day (QD), force-titrated to 80 mg
      at week 4. CLD 25 mg QD could be added (weeks 8-22), if required, to reach
      target, followed by additional antihypertensives from week 12. At the end of the
      open-label phase, mean change in systolic BP (SBP)/DBP from baseline was -23/-16
      mm Hg. The most common adverse events, irrespective of treatment, were dizziness
      (8.9%) and headache (7.2%). Serious AEs were reported in eight patients (1.9%).
      Consecutive creatinine elevations >=50% with values exceeding the upper limit of
      normal (ULN) were reported in nine (2.2%) patients. All returned to below the 50%
      threshold; most also returned to below the ULN after drug discontinuation. Mean
      DBP was maintained through the reversal phase in patients receiving AZL-M, but
      increased with placebo (difference: -7.8 mm Hg, 95% confidence interval, -9.8 to 
      5.8; P<.001). AZL-M alone or with CLD showed good long-term safety and stable BP
      improvements in a titrate-to-target approach. BP improvements caused by AZL-M
      therapy were safely reversible upon AZL-M withdrawal.

PMID- 25619411
TI  - Non-contact low-frequency ultrasound therapy compared with UK standard of care
      for venous leg ulcers: a single-centre, assessor-blinded, randomised controlled
      trial.
AB  - 'Hard-to-heal' wounds are those which fail to heal with standard therapy in an
      orderly and timely manner and may warrant the use of advanced treatments such as
      non-contact low-frequency ultrasound (NLFU) therapy. This evaluator-blinded,
      single-site, randomised controlled trial, compared NLFU in addition to UK
      standard of care [SOC: (NLFU + SOC)] three times a week, with SOC alone at least
      once a week. Patients with chronic venous leg ulcers were eligible to
      participate. All 36 randomised patients completed treatment (17 NLFU + SOC, 19
      SOC), and baseline demographics were comparable between groups. NLFU + SOC
      patients showed a -47% (SD: 38%) change in wound area; SOC, -39% (38%) change;
      and difference, -7.4% [95% confidence intervals (CIs) -33.4-18.6; P = 0.565]. The
      median number of infections per patient was two in both arms of the study and
      change in quality of life (QoL) scores was not significant (P = 0.490). NLFU +
      SOC patients reported a substantial mean (SD) reduction in pain score of -14.4
      (14.9) points, SOC patients' pain scores reduced by -5.3 (14.8); the difference
      was -9.1 (P = 0.078). Results demonstrated the importance of high-quality wound
      care. Outcome measures favoured NLFU + SOC over SOC, but the differences were not
      statistically significant. A larger sample size and longer follow-up may reveal
      NLFU-related improvements not identified in this study. 

PMID- 25619412
TI  - Effect of hematocrit on blood dynamics on a compact disc platform.
AB  - We investigate blood flow dynamics on a rotationally actuated lab-on-a-compact
      disk (LOCD) platform, as a function of the hematocrit level of the blood sample.
      In particular, we emphasize the resultant implications on the critical fluidic
      parameters, such as on burst frequency and volumetric flow rate. Our results can
      be utilized as a characteristic guideline to predict the hematological parameters
      of a given small amount of blood sample from the observed flow characteristics,
      and can give rise to a new paradigm of medical diagnostics driven by interactions
      between blood rheology and rotational forces on an inexpensive platform, with
      minimal sample consumption. 

PMID- 25619413
TI  - Fast-response room temperature hydrogen gas sensors using platinum-coated spin
      capable carbon nanotubes.
AB  - We report the properties of a hydrogen (H2) gas sensor based on platinum (Pt)
      coated carbon nanotubes (CNTs) in this paper. To fabricate the Pt-CNT composite
      sensor, a highly aligned CNT sheet was prepared on a glass substrate from a spin
      capable CNT forest, followed by electrobeam (e-beam) deposition of Pt layers onto
      the CNT sheet. To investigate the effect of Pt on the response of the sensor, Pt
      layers of different thicknesses were deposited on the CNT sheets. A Pt thickness
      of 6 nm yielded the highest response for H2 detection, whereas Pt layers thinner
      or thicker than 6 nm led to a reduction of the surface area for gas adsorption
      and, consequently, decreased response. The Pt-CNT composite sensor detects H2
      concentrations of 3-33% at room temperature and shows reproducible behavior with
      fast response and recovery times. 

PMID- 25619414
TI  - Situs Inversus With Pulmonary Atelectasis.

PMID- 25619415
TI  - Pleural effusion formation in the course of myeloma.

PMID- 25619416
TI  - Pneumomediastinum and subcutaneous emphysema: A rare complication of dental
      extraction.

PMID- 25619417
TI  - Multiple Giant Diverticula of the Bronchus.

PMID- 25619418
TI  - Peripheral Intrapulmonary Lipoma: A Case Report.

PMID- 25619419
TI  - Tampering with cell division by using small-molecule inhibitors of CDK-CKS
      protein interactions.
AB  - Cyclin-dependent kinases (CDKs) control many cellular processes and are
      considered important therapeutic targets. Large collections of inhibitors
      targeting CDK active sites have been discovered, but their use in chemical
      biology or drug development has been often hampered by their general lack of
      specificity. An alternative approach to develop more specific inhibitors is
      targeting protein interactions involving CDKs. CKS proteins interact with some
      CDKs and play important roles in cell division. We discovered two small-molecule
      inhibitors of CDK-CKS interactions. They bind to CDK2, do not inhibit its
      enzymatic activity, inhibit the proliferation of tumor cell lines, induce an
      increase in G1 and/or S-phase cell populations, and cause a decrease in CDK2,
      cyclin A, and p27(Kip1) levels. These molecules should help decipher the complex
      contributions of CDK-CKS complexes in the regulation of cell division, and they
      might present an interesting therapeutic potential. 

PMID- 25619423
TI  - meso-Salicylaldehyde substituted BODIPY as a chemodosimetric sensor for cyanide
      anions.
AB  - The meso-salicylaldehyde substituted BODIPY was synthesized over a sequence of
      steps and characterized by X-ray crystallography, mass, NMR, absorption,
      fluorescence and electrochemical techniques. The crystal structure showed the
      presence of strong intramolecular hydrogen bonding between hydroxyl and formyl
      groups, which induces rigidity in the BODIPY core and makes the BODIPY relatively
      more fluorescent than the meso-phenyl BODIPY. Our studies showed that the meso
      salicylaldehyde BODIPY can be used as a specific chemidosimetric sensor for CN(-)
      ions. The presence of a hydroxyl group adjacent to a formyl group helps in
      activating the formyl group for a nucleophilic attack. Upon addition of the CN(-)
      ion to the meso-salicylaldehyde BODIPY, the CN(-) ion attacks the formyl group
      and converts it to the cyanohydrin group. This irreversible reaction was
      monitored by following the changes in absorption, fluorescence and
      electrochemical properties and the results support the view that the meso
      salicylaldehyde substituted BODIPY can be used as a specific chemodosimetric
      sensor for CN(-) ions. To substantiate the role of the hydroxyl group, we also
      prepared the meso(m-formylphenyl) BODIPY which contains only the formyl group on
      meso-phenyl, and our studies indicated that the meso(m-formylphenyl) BODIPY
      cannot be used as a chemodosimetric sensor for CN(-) ions, as verified by
      absorption and emission studies. 

PMID- 25619422
TI  - Protection of vascular endothelial cells from high glucose-induced cytotoxicity
      by emodin.
AB  - Induction of endothelial cytotoxicity by hyperglycemia in diabetes has been
      widely accepted. Emodin is a natural anthraquinone in rhubarb used for treatment
      of diabetes, but its mechanism of action is not fully understood. This study
      aimed to examine the potential beneficial effects of emodin on endothelial
      cytotoxicity caused by high glucose milieu. Culture of human umbilical vein
      endothelial cells (HUVECs) with high concentrations of glucose resulted in damage
      to the cells, leading to decreased formazan products by 14-27%, reduced DNA
      contents by 12-19%, and increased hypodiploid apoptosis by 40-109%. These adverse
      effects of high glucose could be prevented to a large extent by co-culture with 3
      MUM of emodin which per se did not affect HUVECs viability. In addition, CCL5
      expression of HUVECs cultured in high glucose medium was significantly elevated
      at both mRNA and protein levels, an effect abolished after treatment with emodin.
      Moreover, the enhanced adhesion of monocytes to HUVECs (2.1-2.2 fold over
      control) and elevated chemotaxis activities (2.3-2.4 fold over control) in HUVECs
      cultured in high glucose medium were completely reversed by emodin. Emodin also
      suppressed activation of p38 MAPK and ERK1/2 due to high glucose. Our data
      demonstrated that endothelial cytotoxicity occurred clearly when HUVECs were
      exposed to high glucose milieu and emodin was able to alleviate the impairments.
      The protective effects of emodin might be related to the inhibition of CCL5
      expression and subsequent cell stress/inflammatory events possibly mediated by
      activation of MAPK signaling pathways.

PMID- 25619424
TI  - Complete switch from alpha-2,3- to alpha-2,6-regioselectivity in Pasteurella
      dagmatis beta-D-galactoside sialyltransferase by active-site redesign.
AB  - Structure-guided active-site redesign of a family GT-80 beta-D-galactoside
      sialyltransferase (from Pasteurella dagmatis) to change enzyme regioselectivity
      from alpha-2,3 in the wild type to alpha-2,6 in a P7H-M117A double mutant is
      reported. Biochemical data for sialylation of lactose together with protein
      crystal structures demonstrate highly precise enzyme engineering.

PMID- 25619425
TI  - Non-union in 3 of 15 osteotomies of the distal radius without bone graft.
AB  - BACKGROUND AND PURPOSE: Open-wedge osteotomies of the distal radius create a void
      that is usually filled with either iliac crest bone graft or bone substitute.
      Previous studies have suggested that this is unnecessary. We investigated the
      safety of omitting the filling procedure. PATIENTS AND METHODS: We included 15
      patients with a dorsal malunion of a distal radius fracture. A palmar approach
      and angle-stable plates were used. The patients were followed until there was
      radiographic and clinical healing. RESULTS: Non-union occurred in 3 of the 15
      patients. The study, which had been planned to include 25 patients, was then
      discontinued. 6 osteotomies created a trapezoid void (no cortical contact); 3 of
      these did not unite after the index procedure (p = 0.04), but did subsequently,
      after autogenous bone grafting. A trapezoid void was significantly associated
      with non-union (p = 0.04). INTERPRETATION: When a trapezoid defect is created,
      one should consider bone substitute or autogenous bone graft. This has been shown
      to be safe in other studies.

PMID- 25619426
TI  - Phytanic acid induces Neuro2a cell death via histone deacetylase activation and
      mitochondrial dysfunction.
AB  - Phytanic acid is a branched fatty acid that is a metabolic intermediate of
      chlorophyll. In this study, the effects of phytanic acid on Histone deacetylase
      (Hdac) activity were examined in an in vitro enzyme assay and in neuronal Neuro2a
      cells. Several fatty acids have been shown to be Hdac inhibitors, but phytanic
      acid enhanced the enzyme activity in vitro. In Neuro2a cells, phytanic acid
      significantly reduced histone acetylation and induced cell death, which was
      inhibited by an Hdac inhibitor, sodium butyrate. Theophylline, a common Hdac
      activator, had a similar effect on Neuro2a cell viability, and this effect was
      also inhibited by sodium butyrate. Phytanic acid decreased the level of
      intracellular active mitochondria, while butyrate increased this level. The
      cytotoxic effect of phytanic acid was also abolished by a caspase-9 inhibitor.
      Apicidin, a Hdac2- and 3-specific inhibitor, reduced the cellular toxicity, which
      suggests that the toxicity of phytanic acid depends on activation of the Hdac2
      and 3 subtypes. Overall, these results show that phytanic acid induces
      mitochondrial abnormality and cell death via activation of Hdac2, 3 in Neuro2a
      cells. This effect of Hdac activation by phytanic acid may produce neuronal
      damage in Refsum disease and other peroxisomal disorders, which is caused by
      accumulation of phytanic acid. 

PMID- 25619427
TI  - Self-crack-filled graphene films by metallic nanoparticles for high-performance
      graphene heterojunction solar cells.
AB  - Graphene, with cracks filled with gold nanoparticles, is grown by chemical vapor
      deposition on a Cu substrate. The crack-filled graphene not only exhibits
      superior electrical properties but also forms a better junction with other
      semiconductors. A high-quality crack-filled graphene/Si Schottky junction solar
      cell is achieved, demonstrating the highest fill factor (0.79) and best
      efficiency (12.3%). 

PMID- 25619428
TI  - Synthesis of double-shelled SnO2 nano-polyhedra and their improved gas sensing
      properties.
AB  - A new type of non-spherical SnO2 hollow structure with double-shelled and
      mesoporous shells was prepared via a sacrifice template strategy in the case of
      SnO2, which shows high response and good selectivity to toluene. 

PMID- 25619429
TI  - The illumination characteristics of operative microscopes.
AB  - PURPOSE: Modern operative microscopes use light sources which possess the power
      to severely damage underlying tissue. Currently, manufacturers provide a safety
      warning of this possibility. However, they are unable to suggest specific
      settings due to a stated "lack of scientific publications on this topic". We aim
      to radiometrically evaluate multiple otologic microscopes at variables which
      effect irradiance in order to determine reference emissions levels and provide
      guidelines for improved intraoperative safety. MATERIALS AND METHODS: The optical
      radiance of four otologic microscopes was evaluated at variable field
      illumination sizes (spot size), intensity settings and working distances. The
      spectral emission of each microscope was separately measured. The energy absorbed
      in skin with representative properties was then calculated as a function of time
      for each microscope by accounting for the emission spectrum of the microscope and
      the absorption spectrum of skin. RESULTS: Microscopes showed a wide range of
      optical radiance based on model, spots size, intensity setting and working
      distances. Spectral emission of all four microscopes was centered in the visible
      spectrum with minimal ultraviolet or infrared contribution. A large amount of
      energy is absorbed by skin during usage of operative microscopes. The highest
      calculated absorption at 200 min of use was 736.26 J/cm(2). CONCLUSIONS:
      Operative microscopes have the ability to cause patient morbidity secondary to
      the energy they impart. In an effort to decrease potential injury we recommend
      that physicians be aware of their microscopes properties and how to control
      variables which effect irradiance of the skin.

PMID- 25619430
TI  - Hypothalamic-pituitary-adrenal axis activity in patients with pathological
      gambling and internet use disorder.
AB  - Alterations in secretion of stress hormones within the hypothalamic-pituitary
      adrenal (HPA) axis have repeatedly been found in substance-related addictive
      disorders. It has been suggested that glucocorticoids might contribute to the
      development and maintenance of substance use disorders by facilitatory effects on
      behavioral responses to substances of abuse. The objective of this pilot study
      was to investigate HPA axis activity in patients with non-substance-related
      addictive disorders, i.e. pathological gambling and internet use disorder. We
      measured plasma levels of copeptin, a vasopressin surrogate marker,
      adrenocorticotropic hormone (ACTH) and cortisol in male patients with
      pathological gambling (n=14), internet use disorder (n=11) and matched healthy
      controls for pathological gambling (n=13) and internet use disorder (n=10).
      Plasma levels of copeptin, ACTH and cortisol in patients with pathological
      gambling or internet use disorder did not differ among groups. However, cortisol
      plasma levels correlated negatively with the severity of pathological gambling as
      measured by the PG-YBOCS. Together with our findings of increased serum levels of
      brain-derived neurotrophic factor (BDNF) in pathological gambling but not
      internet use disorder, these results suggest that the pathophysiology of
      pathological gambling shares some characteristics with substance-related
      addictive disorders on a neuroendocrinological level, whereas those similarities
      could not be observed in internet use disorder. 

PMID- 25619431
TI  - The many faces of oxytocin: implications for psychiatry.
AB  - Oxytocin is known as the 'love hormone' due its role in promoting mother-child
      and pair bonding. More recent research indicates that oxytocin may have broader
      pro-social effects on behavior and cognition, which points towards oxytocin's
      potential as an agent to help improve social cognition and functioning in
      psychiatric disorders such as schizophrenia and autism. However, new research on
      oxytocin has also uncovered a 'darker side', including oxytocin's possible role
      in social out-grouping and envy. Instead of a simple view of oxytocin as 'good'
      or 'bad', a more accurate depiction of oxytocin's role in social processing
      likely involves the presence of moderating factors. We review moderation effects
      in oxytocin and their implications for psychiatry. One implication is that,
      across diagnostic categories, oxytocin administration may have positive effects
      for patients with social cognitive deficits but negative effects for patients
      with social cognitive bias. We conclude that future intervention studies should
      use methods such as signal detection to measure both deficit and bias parameters
      of social cognition and to evaluate potential individual and contextual
      moderators both within and between psychiatric diagnoses in order to determine
      for whom oxytocin treatment may be beneficial and for whom it may actually be
      harmful.

PMID- 25619432
TI  - Effects of remission speed and improvement of cognitive functions of depressed
      patients.
AB  - Major depressive disorder (MDD) presents neuropsychological alterations which
      improve after the treatment, but it might be mediated by clinical variables. Our
      goal is to study whether the speed of remission of MDD bears any relation to the
      improvement of the patients' cognitive functioning after a successful treatment.
      We carried out clinical and neuropsychological assessments of 51 patients with
      MDD. After these procedures they underwent a 24-week treatment with fluoxetine,
      and were assessed again with the same battery used prior to treatment. They were
      arranged into three groups according to how rapid their symptoms remitted. The
      patients with a rapid remission presented improvements in working memory, speed
      of information processing, and some executive functions, unlike the other groups.
      Rapid remitters also improved in episodic memory and executive functions more
      than the other patients.

PMID- 25619433
TI  - Delay in initiation of clozapine: a retrospective study from a tertiary care
      hospital in North India.
AB  - This study aimed to assess the delay in initiation of clozapine, number of
      adequate antipsychotic trials prior to starting clozapine and practice of
      polypharmacy prior to starting clozapine. A retrospective study design was
      followed. Treatment records of 200 patients started on clozapine during the
      period of January 2006-June 2014 were reviewed. The mean delay in clozapine
      initiation was 1.93 (S.D. 1.82) years and median was 1.5 years. Mean of 3 (S.D.
      1.18) adequate antipsychotic trials was given prior to considering clozapine and
      27.5% patients had received polypharmacy prior to clozapine. Factors related to
      delay in starting of clozapine included higher age, longer duration of illness,
      age more than 20 years of age, polypharmacy, use of an adequate trial of typical
      antipsychotic medication, patients from urban locality and those with onset of
      illness prior to introduction of clozapine into Indian market. Findings of the
      present study suggest that there is a delay of 1.5-2 years in starting of
      clozapine and about one-fourth of patients receive polypharmacy prior to
      receiving clozapine. These finding suggests that there is a need to change the
      prescribing habits to reduce the delay in starting of clozapine. 

PMID- 25619435
TI  - Differences in the internal structure of hallucinatory experiences between
      clinical and nonclinical populations.
AB  - We investigated differential patterns of hallucinatory experiences between
      nonclinical and clinical samples. A total of 223 nonclinical individuals (108
      females) and 111 subjects with schizophrenia (54 females) completed the Launay
      Slade Hallucination Scale-Revised (LSHS-R) and Perceptual Aberration Scale (PAS).
      The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) was used for the
      nonclinical group, and the Positive and Negative Syndrome Scale (PANSS)
      hallucination item was used for the clinical group. Cronbach's alpha values
      showed good internal consistency for the LSHS-R. In the two groups, significant
      associations were found between LSHS-R and PAS scores. Two factors were extracted
      through a principal component analysis (PCA) in the nonclinical group, and three
      factors were identified in the clinical group. The results of a hierarchical
      cluster analysis (HCA) revealed that a perception-cognition dimension was clear
      cluster discriminating element for the nonclinical group, whereas alterations in
      perception-cognition dimension were characteristic in cluster structure of the
      clinical group. Our findings suggest that the nature of hallucinatory experiences
      may differ qualitatively between a nonclinical population and subjects with
      schizophrenia. Perceptual or cognitive aberrations may add a psychopathologic
      dimension to hallucinatory experiences. Exploring the internal structure of
      hallucinatory experiences may provide explanatory insight into these experiences
      in the general population.

PMID- 25619434
TI  - Abnormal movements in first-episode, nonaffective psychosis: dyskinesias,
      stereotypies, and catatonic-like signs.
AB  - Motor abnormalities represent a neurobehavioral domain of signs intrinsic to
      schizophrenia-spectrum disorders, though they are commonly attributed to
      medication side effects and remain understudied. Individuals with first-episode
      psychosis represent an ideal group to study innate movement disorders due to
      minimal prior antipsychotic exposure. We measured dyskinesias, stereotypies, and
      catatonic-like signs and examined their associations with: (1) age at onset of
      psychotic symptoms and duration of untreated psychosis; (2) positive, negative,
      and disorganized symptoms; (3) neurocognition; and (4) neurological soft signs.
      Among 47 predominantly African American first-episode psychosis patients in a
      public-sector hospital, the presence and severity of dyskinesias, stereotypies,
      and catatonic-like features were assessed using approximately 30-min video
      recordings. Movement abnormalities were rated utilizing three scales (Dyskinesia
      Identification System Condensed User Scale, Stereotypy Checklist, and Catatonia
      Rating Scale). Correlational analyses were conducted. Scores for each of three
      movement abnormality types were modestly inter-correlated (r=0.29-0.40).
      Stereotypy score was significantly associated with age at onset of psychotic
      symptoms (r=0.32) and positive symptom severity scores (r=0.29-0.41). There were
      no meaningful or consistent associations with negative symptom severity,
      neurocognition, or neurological soft signs. Abnormal movements appear to
      represent a relatively distinct phenotypic domain deserving of further research. 

PMID- 25619436
TI  - Disordered eating attitudes, alexithymia and suicide probability among Turkish
      high school girls.
AB  - We aimed to examine association between disordered eating attitudes (DEAs),
      alexithymia and suicide probability among adolescent females and to explore
      potential link between alexithymia and suicide probability in subjects with DEAs.
      381 female students completed Eating Attitude Test (EAT-26), Toronto Alexithymia
      Scale (TAS-20) and Suicide Probability Scale (SPS). It was found that 13.2%
      (n=52) of the subjects have DEAs. Results indicated that total TAS-20 score and
      scores of Difficulty in Identifying Feelings (DIF) and Difficulty in Describing
      Feelings (DDF) subscales were significantly higher in DEAs group than in those
      non DEAs group (p<0.05). Additionally, total SPS score (p<0.001), Hopelessness
      (p=0.001), Suicide Ideation (p<0.001) and Hostility (p=0.003) subscales scores of
      SPS were significantly higher in the alexithymic DEAs than the non-alexithymic
      DEAs group. In order to control potential effect of depression, SPS subscales
      were used as covariate factors in ANCOVA. Negative Self-Evaluation subscale
      yielded a statistically significant difference between groups, other subscales
      did not. Results point out these; DEAs are relatively frequent phenomenon among
      female students in Turkey and presence of alexithymia was associated with an
      increased suicide probability in adolescents with DEAs. The results should be
      evaluated taking into account that depressive symptomatology was not assessed
      using a depression scale. 

PMID- 25619439
TI  - Risk factors for idiopathic sudden sensorineural hearing loss and their
      association with clinical outcome.
AB  - BACKGROUND: Sudden sensorineural hearing loss (ISSHL) is idiopathic in 85% of
      cases and cochlear micro-thrombosis has been hypothesized as pathogenic
      mechanism. The role of thrombophilia and cardiovascular risk factors in ISSHL is
      controversial and whether these risk factors influence the clinical outcome of
      ISSHL is unknown. METHODS: and patients To investigate the role of thrombophilia
      and cardiovascular risk factors in ISSHL and to evaluate their influence on
      clinical outcome of the disease, 118 patients with a first episode of ISSHL and
      415 healthy controls were investigated. Thrombophilia screening included
      measurements of antithrombin, protein C, protein S, factor V Leiden, prothrombin
      G20210A, antiphospholipid antibodies, fibrinogen, factor VIII and homocysteine.
      RESULTS: Deficiencies of antithrombin, protein C or S taken together, high factor
      VIII and hyperhomocysteinemia were significantly associated with ISSHL (OR
      [95%CI]: 7.55 [1.05-54.47], 2.91 [1.31-6.44] and 2.69 [1.09-6.62], respectively),
      whereas no association was found with the remaining thrombophilia markers. A 2
      fold increased risk of poor clinical outcome was observed for every 5 MUmol/L
      increase of fasting homocysteine levels (adjusted OR [95%CI]) 2.13 [1.02-4.44])
      until levels of approximately 15 MUmol/L, then the risk increased slowly.
      Cardiovascular risk factors (arterial hypertension, hyperlipidemia, diabetes and
      smoking) were associated with an increased risk of ISSHL (OR [95%CI] 1.88 [1.17
      3.03]) and with a poor clinical outcome (OR [95%CI] 2.22 [0.93-5.26]).
      CONCLUSIONS: Hyperhomocysteinemia, high factor VIII and, with more uncertainty,
      deficiencies of antithrombin, protein C or S and cardiovascular risk factors
      increase the risk of ISSHL. Hyperhomocysteinemia and cardiovascular risk factors
      are associated with a poor clinical outcome of ISSHL.

PMID- 25619437
TI  - Age- and pregnancy-associated DNA methylation changes in mammary epithelial
      cells.
AB  - Postnatal mammary gland development and differentiation occur during puberty and
      pregnancy. To explore the role of DNA methylation in these processes, we
      determined the genome-wide DNA methylation and gene expression profiles of
      CD24(+)CD61(+)CD29(hi), CD24(+)CD61(+)CD29(lo), and CD24(+)CD61(-)CD29(lo) cell
      populations that were previously associated with distinct biological properties
      at different ages and reproductive stages. We found that pregnancy had the most
      significant effects on CD24(+)CD61(+)CD29(hi) and CD24(+)CD61(+)CD29(lo) cells,
      inducing distinct epigenetic states that were maintained through life. Integrated
      analysis of gene expression, DNA methylation, and histone modification profiles
      revealed cell-type- and reproductive-stage-specific changes. We identified p27
      and TGFbeta signaling as key regulators of CD24(+)CD61(+)CD29(lo) cell
      proliferation, based on their expression patterns and results from mammary gland
      explant cultures. Our results suggest that relatively minor changes in DNA
      methylation occur during luminal differentiation compared with the effects of
      pregnancy on CD24(+)CD61(+)CD29(hi) and CD24(+)CD61(+)CD29(lo) cells. 

PMID- 25619440
TI  - Correlation of coagulation markers and 4F-PCC-mediated reversal of rivaroxaban in
      a rabbit model of acute bleeding.
AB  - INTRODUCTION: Rivaroxaban is an oral, selective direct factor Xa inhibitor
      approved for several indications in patients at risk of thrombotic events. One
      limitation of its clinical use is the lack of data pertaining to its reversal in
      situations where urgent response is critical (e.g. acute bleeding events or
      emergency surgery). MATERIALS AND METHODS: This study assessed the effectiveness
      of a four-factor prothrombin complex concentrate (4F-PCC;
      Beriplex((r))/Kcentra((r))) for the reversal of rivaroxaban-associated bleeding
      in an in vivo rabbit model, and evaluated the correlations between in vitro
      coagulation parameters and haemostasis in vivo. RESULTS: Administration of single
      intravenous doses of rivaroxaban (150-450 MUg/kg) resulted in increased and
      prolonged bleeding following standardised kidney incision. Pre-incision treatment
      with 4F-PCC (25-100 IU/kg) resulted in a dose-dependent reversal of rivaroxaban
      (150 and 300 MUg/kg)-associated increases in time to haemostasis and blood loss;
      no reversal was seen at the highest rivaroxaban dose (450 MUg/kg). Of the in
      vitro biomarkers tested, thrombin generation and whole-blood clotting time
      correlated well with in vivo measures of 4F-PCC-mediated effects. Thrombin
      generation was highly reagent-dependent, with the assay initiated using the
      phospholipid-only reagent being the most predictive of effective haemostasis in
      vivo. CONCLUSIONS: In summary, in a rabbit model of acute bleeding, treatment
      with 4F-PCC reduced bleeding to control levels following rivaroxaban 150 MUg/kg
      and 300 MUg/kg administration.

PMID- 25619441
TI  - Fully automatic rhythm analysis during chest compression pauses.
AB  - AIM: Chest compression artefacts impede a reliable rhythm analysis during
      cardiopulmonary resuscitation (CPR). These artefacts are not present during
      ventilations in 30:2 CPR. The aim of this study is to prove that a fully
      automatic method for rhythm analysis during ventilation pauses in 30:2 CPR is
      reliable an accurate. METHODS: For this study 1414min of 30:2 CPR from 135 out-of
      hospital cardiac arrest cases were analysed. The data contained 1942 pauses in
      compressions longer than 3.5s. An automatic pause detector identified the pauses
      using the transthoracic impedance, and a shock advice algorithm (SAA) diagnosed
      the rhythm during the detected pauses. The SAA analysed 3-s of the ECG during
      each pause for an accurate shock/no-shock decision. RESULTS: The sensitivity and
      PPV of the pause detector were 93.5% and 97.3%, respectively. The sensitivity and
      specificity of the SAA in the detected pauses were 93.8% (90% low CI, 90.0%) and
      95.9% (90% low CI, 94.7%), respectively. Using the method, shocks would have been
      advanced in 97% of occasions. For patients in nonshockable rhythms, rhythm
      reassessment pauses would be avoided in 95.2% (95% CI, 91.6-98.8) of occasions,
      thus increasing the overall chest compression fraction (CCF). CONCLUSION: An
      automatic method could be used to safely analyse the rhythm during ventilation
      pauses. This would contribute to an early detection of refibrillation, and to
      increase CCF in patients with nonshockable rhythms.

PMID- 25619442
TI  - Comparison of out-of-hospital cardiac arrest occurring before and after paramedic
      arrival: epidemiology, survival to hospital discharge and 12-month functional
      recovery.
AB  - BACKGROUND: Despite immediate resuscitation, survival rates following out-of
      hospital cardiac arrests (OHCA) witnessed by emergency medical service (EMS) are
      reportedly low. We sought to compare survival and 12-month functional recovery
      outcomes for OHCA occurring before and after EMS arrival. METHODS: Between 1st
      July 2008 and 30th June 2013, we included 8648 adult OHCA cases receiving an EMS
      attempted resuscitation from the Victorian Ambulance Cardiac Arrest Registry, and
      categorised them into five groups: bystander witnessed cases+/-bystander CPR,
      unwitnessed cases+/-bystander CPR, and EMS witnessed cases. The main outcomes
      were survival to hospital and survival to hospital discharge. Twelve-month
      survival with good functional recovery was measured in a sub-group of patients
      using the Extended Glasgow Outcome Scale (GOSE). RESULTS: Baseline and arrest
      characteristics differed significantly across groups. Unadjusted survival
      outcomes were highest among bystander witnessed cases receiving bystander CPR and
      EMS witnessed cases, however outcomes differed significantly between these
      groups: survival to hospital (46.0% vs. 53.4% respectively, p<0.001); survival to
      hospital discharge (21.1% vs. 34.9% respectively, p<0.001). When compared to
      bystander witnessed cases receiving bystander CPR, EMS witnessed cases were
      associated with a significant improvement in the risk adjusted odds of survival
      to hospital (OR 2.02, 95% CI: 1.75-2.35), survival to hospital discharge (OR
      6.16, 95% CI: 5.04-7.52) and survival to 12 months with good functional recovery
      (OR 5.56, 95% CI: 4.18-7.40). CONCLUSION: When compared to OHCA occurring prior
      to EMS arrival, EMS witnessed arrests were associated with significantly higher
      survival to hospital discharge rates and favourable neurological recovery at 12
      month post-arrest.

PMID- 25619443
TI  - Sinus bradycardia during hypothermia in comatose survivors of out-of-hospital
      cardiac arrest - a new early marker of favorable outcome?
AB  - BACKGROUND: Bradycardia is a common finding in patients undergoing therapeutic
      hypothermia (TH) following out-of-hospital cardiac arrest (OHCA), presumably as a
      normal physiological response to low body temperature. We hypothesized that a
      normal physiological response with sinus bradycardia (SB) indicates less
      neurological damage and therefore would be associated with lower mortality.
      METHODS: We studied 234 consecutive comatose survivors of OHCA with presumed
      cardiac etiology and shockable primary rhythm, who underwent a full 24-h TH
      protocol (33 degrees C) at a tertiary heart center (years: 2004-2010). Primary
      endpoint was 180-day mortality; secondary endpoint was favorable neurological
      outcome (180-day cerebral performance category: 1-2). RESULTS: SB, defined as
      sinus rhythm <50 beats per minute during TH, was present in 115 (49%) patients.
      Baseline characteristics including sex, witnessed arrest, bystander
      cardiopulmonary resuscitation and time to return of spontaneous circulation were
      not different between SB- and no-SB patients. However, SB-patients were younger,
      57+/-14 vs. 63+/-14 years, p<0.001 and less frequently had known heart failure
      (7% vs. 20%, p<0.01). Patients experiencing SB during the hypothermia phase of TH
      had a 17% 180-day mortality rate compared to 38% in no-SB patients (p<0.001),
      corresponding to a 180-day hazard ratio (HRadjusted=0.45 (0.23-0.88, p=0.02)) in
      the multivariable analysis. Similarly, SB during hypothermia was directly
      associated with lower odds of unfavorable neurological outcome (ORunadjusted=0.42
      (0.23-0.75, p<0.01). CONCLUSION: Sinus bradycardia during therapeutic hypothermia
      is independently associated with a lower 180-day mortality rate and may thus be a
      novel, early marker of favorable outcome in comatose survivors of OHCA.

PMID- 25619444
TI  - Outcome prediction and temperature dependency of MR-proANP and Copeptin in
      comatose resuscitated patients.
AB  - OBJECTIVE: To evaluate the prognostic potential of serum C-terminal
      provasopressin (CT-proAVP or Copeptin) and midregional pro-A-type natriuretic
      peptide (MR-proANP) to predict neurological outcome following resuscitation from
      cardiac arrest. METHODS: In this prospective observational study, we employed
      novel ultra sensitive immunoassay technology to examine serial serum samples from
      134 cardiac arrest patients. Patients were either allocated to mild therapeutic
      hypothermia using an endovascular device or normothermia. Serial blood samples
      were obtained from resuscitated cardiac arrest survivors during their first 7
      days in an intensive care unit, and serum Copeptin and MR-proANP were measured.
      Cerebral function assessments were made using cerebral performance categorization
      (CPC) at discharge from hospital. Copeptin and MR-proANP data were analyzed using
      dichotomized CPC scores (1-2 versus 3-5). RESULTS: Sixty-nine patients (51%) had
      a poor outcome (CPC 3-5) at hospital discharge. MR-proANP and Copeptin peaked on
      day 1 (i.e. 0-24h) with the medians being 249.3pmol/L and 77.2pmol/L,
      respectively. In the first 48h maximum levels of MR-proANP and Copeptin showed an
      AUC in the ROC of 0.743 (95% CI: 0.658-0.828) and 0.677 (95% CI: 0.583-0.771).
      Binary logistic regression revealed MR-proANP and Copeptin within 48h after ROSC
      being significantly associated with functional outcome (p<0.05). Copeptin within
      48h was also associated with outcome in the hypothermia group (p<0.05).
      CONCLUSION: Systemic levels of MR-proANP and Copeptin peak early in cardiac
      arrest patients in the 48h post-resuscitation period. MR-proANP and Copeptin were
      highly predictive for poor outcome in comatose resuscitated patients.

PMID- 25619446
TI  - The impact of early gut microbiota modulation on the risk of child disease: alert
      to accuracy in probiotic studies.
AB  - The composition of the gut microbiota, and thus also the modification of the gut
      microbiota by specific probiotics or prebiotics early in life, may have an impact
      on the risk of disease in the child. Above the impact on gut microecology,
      probiotic effects have been attributed to restoration to normal of increased
      intestinal permeability, improvement of the intestine's immunological barrier
      functions, alleviation of the intestinal inflammatory response, and reduced
      generation of proinflammatory cytokines characteristic of local and systemic
      allergic inflammation. Recent demonstrations from experimental and clinical
      studies suggest that the gut microbiota is also involved in the control of body
      weight and energy metabolism, affecting the two main causes of obesity: energy
      acquisition and storage, and contributing to insulin resistance and the
      inflammatory state characterising obesity. Current research focuses both on
      characterising specific probiotic strains and on how the food matrix and the
      dietary content interacts with the most efficient probiotic strains. It is
      important to characterise each probiotic to species and strain level and to
      select strains with documented properties, the probiotic potential being strain
      specific. As any proof of causality requires clinical intervention studies in
      humans in different populations, rigorous and detailed documentation will enhance
      reproducibility and circumvent confusion. 

PMID- 25619445
TI  - The relative clinical effectiveness and cost-effectiveness of three contrasting
      approaches to partner notification for curable sexually transmitted infections: a
      cluster randomised trial in primary care.
AB  - BACKGROUND: Partner notification is the process of providing support for,
      informing and treating sexual partners of individuals who have been diagnosed
      with sexually transmitted infections (STIs). It is traditionally undertaken by
      specialist sexual health services, and may involve informing a partner on a
      patient's behalf, with consent. With an increasing proportion of STIs diagnosed
      in general practice and other community settings, there is a growing need to
      understand the best way to provide partner notification for people diagnosed with
      a STI in this setting using a web-based referral system. OBJECTIVE: We aimed to
      compare three different approaches to partner notification for people diagnosed
      with chlamydia within general practice. DESIGN: Cluster randomised controlled
      trial. SETTING: General practices in England and, within these, patients tested
      for and diagnosed with genital chlamydia or other bacterial STIs in that setting
      using a web-based referral system. INTERVENTIONS: Three different approaches to
      partner notification: patient referral alone, or the additional offer of either
      provider referral or contract referral. MAIN OUTCOME MEASURES: (1) Number of main
      partners per index patient treated for chlamydia and/or gonorrhoea/non-specific
      urethritis/pelvic inflammatory disease; and (2) proportion of index patients
      testing negative for the relevant STI at 3 months. RESULTS: As testing rates for
      chlamydia were far lower than expected, we were unable to scale up the trial,
      which was concluded at pilot stage. We are not able to answer the original
      research question. We present the results of the work undertaken to improve
      recruitment to similar studies requiring opportunistic recruitment of young
      people in general practice. We were unable to standardise provider and contract
      referral separately; however, we also present results of qualitative work aimed
      at optimising these interventions. CONCLUSIONS: External recruitment may be
      required to facilitate the recruitment of young people to research in general
      practice, especially in sensitive areas, because of specific barriers experienced
      by general practice staff. Costs need to be taken into account together with
      feasibility considerations. Partner notification interventions for bacterial STIs
      may not be clearly separable into the three categories of patient, provider and
      contract referral. Future research is needed to operationalise the approaches of
      provider and contract partner notification if future trials are to provide
      generalisable information. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN24160819. FUNDING: This project was funded by the National Institute for
      Health Research Health Technology Assessment programme and will be published in
      full in Health Technology Assessment; Vol. 19, No. 5. See the NIHR Journals
      Library website for further project information.

PMID- 25619447
TI  - A granulocytosis associated with rufinamide: A case report.
AB  - BACKGROUND: Rufinamide, a triazole derivative, is a novel antiepileptic drug
      (AED) chemically unrelated to other current AEDs. Previous studies on pediatric
      epilepsy treatment with rufinamide have demonstrated a frequency of leukopenia as
      an adverse event of 0.5%, and there has been no report of the development of
      agranulocytosis. Here, we report a patient with Lennox-Gastaut syndrome (LGS) who
      developed agranulocytosis associated with fever and skin rash with rufinamide. To
      the best of our knowledge, this is the first reported case of agranulocytosis
      induced by rufinamide. PATIENT: A 10-year-old boy with a history of herpes
      encephalitis at the age of 1 year developed LGS, and was administered rufinamide
      as add-on therapy to valproate, lamotrigine, and clonazepam because of
      difficulties in controlling tonic seizures. Eighteen days after initiation of
      rufinamide, agranulocytosis developed associated with high fever and skin rash,
      all of which resolved after withdrawal of rufinamide. Bone marrow aspiration
      demonstrated normocellular marrow with selective decrease of mature myeloid
      series, and suggested that agranulocytosis was not related to malignancy or
      serious infection. CONCLUSION: This case suggests that rufinamide may induce the
      potentially serious adverse effect of agranulocytosis. Patients should be
      monitored for clinical signs of agranulocytosis and consideration should be given
      to routine blood count determination for early detection of this.

PMID- 25619448
TI  - From lignocellulosic biomass to furans via 5-acetoxymethylfurfural as an
      alternative to 5-hydroxymethylfurfural.
AB  - A facile pathway to furan derivatives from lignocellulosic biomass via 5
      acetoxymethylfurfural (AMF) was developed. AMF possesses advantageous properties
      due to its less-hydrophilic acetoxymethyl group relative to the hydroxymethyl
      group of 5-hydroxymethylfurfural (HMF). The hydrophobicity and chemical stability
      of AMF allowed practical isolation and purification to afford a highly pure
      product of up to 99.9 %. AMF was produced in good to excellent yields under mild
      conditions from 5-chloromethylfurfural (CMF) and alkylammonium acetates, both of
      which could be obtained directly from lignocellulosic biomass. Heterogeneous
      reactions with polymer-supported alkylammonium acetates were also established;
      this showed the feasibility of a continuous process for this pathway. AMF could
      be transformed into various promising furanic compounds, such as 2,5
      furandicarboxylic acid (FDCA), 2,5-furandimethanol (FDM), and 5-hydroxymethyl-2
      furanoic acid (HFA), in high yields. 

PMID- 25619449
TI  - StimDuino: an Arduino-based electrophysiological stimulus isolator.
AB  - BACKGROUND: Electrical stimulus isolator is a widely used device in
      electrophysiology. The timing of the stimulus application is usually automated
      and controlled by the external device or acquisition software; however, the
      intensity of the stimulus is adjusted manually. Inaccuracy, lack of
      reproducibility and no automation of the experimental protocol are disadvantages
      of the manual adjustment. To overcome these shortcomings, we developed StimDuino,
      an inexpensive Arduino-controlled stimulus isolator allowing highly accurate,
      reproducible automated setting of the stimulation current. NEW METHOD: The
      intensity of the stimulation current delivered by StimDuino is controlled by
      Arduino, an open-source microcontroller development platform. The automatic
      stimulation patterns are software-controlled and the parameters are set from
      Matlab-coded simple, intuitive and user-friendly graphical user interface. The
      software also allows remote control of the device over the network. RESULTS:
      Electrical current measurements showed that StimDuino produces the requested
      current output with high accuracy. In both hippocampal slice and in vivo
      recordings, the fEPSP measurements obtained with StimDuino and the commercial
      stimulus isolators showed high correlation. COMPARISON WITH EXISTING METHODS:
      Commercial stimulus isolators are manually managed, while StimDuino generates
      automatic stimulation patterns with increasing current intensity. The pattern is
      utilized for the input-output relationship analysis, necessary for assessment of
      excitability. In contrast to StimuDuino, not all commercial devices are capable
      for remote control of the parameters and stimulation process. CONCLUSIONS:
      StimDuino-generated automation of the input-output relationship assessment
      eliminates need for the current intensity manually adjusting, improves
      stimulation reproducibility, accuracy and allows on-site and remote control of
      the stimulation parameters.

PMID- 25619451
TI  - Modification of foaming properties of soy protein isolate by high ultrasound
      intensity: Particle size effect.
AB  - The effect of high intensity ultrasound (HIUS) may produce structural
      modifications on proteins through a friendly environmental process. Thus, it can
      be possible to obtain aggregates with a determined particle size, and altering a
      defined functional property at the same time. The objective of this work was to
      explore the impact of HIUS on the functionality of a denatured soy protein
      isolate (SPI) on foaming and interfacial properties. SPI solutions at pH 6.9 were
      treated with HIUS for 20 min, in an ultrasonic processor at room temperature, at
      75, 80 and 85 degrees C. The operating conditions were: 20 kHz, 4.27 +/- 0.71 W
      and 20% of amplitude. It was determined the size of the protein particles, before
      and after the HIUS treatment, by dynamic light scattering. It was also analyzed
      the interfacial behavior of the different systems as well as their foaming
      properties, by applying the whipping method. The HIUS treatment and HIUS with
      temperature improved the foaming capacity by alteration of particle size whereas
      stability was not modified significantly. The temperature of HIUS treatment (80
      and 85 degrees C) showed a synergistic effect on foaming capacity. It was found
      that the reduction of particle size was related to the increase of foaming
      capacity of SPI. On the other hand, the invariable elasticity of the interfacial
      films could explain the stability of foams over time.

PMID- 25619452
TI  - Clinical management in hard times.

PMID- 25619450
TI  - Honokiol confers immunogenicity by dictating calreticulin exposure, activating ER
      stress and inhibiting epithelial-to-mesenchymal transition.
AB  - Peritoneal dissemination is a major clinical obstacle in gastrointestinal cancer
      therapy, and it accounts for the majority of cancer-related mortality.
      Calreticulin (CRT) is over-expressed in gastric tumors and has been linked to
      poor prognosis. In this study, immunohistochemistry studies revealed that the up
      regulation of CRT was associated with lymph node and distant metastasis in
      patients with gastric cancer specimens. CRT was significantly down-regulated in
      highly metastatic gastric cancer cell lines and metastatic animal by Honokiol
      treated. Small RNA interference blocking CRT by siRNA-CRT was translocated to the
      cells in the early immunogenic response to Honokiol. Honokiol activated
      endoplasmic reticulum (ER) stress and down-regulated peroxisome proliferator
      activated receptor-gamma (PPARgamma) activity resulting in PPARgamma and CRT
      degradation through calpain-II activity, which could be reversed by siRNA-calpain
      II. The Calpain-II/PPARgamma/CRT axis and interaction evoked by Honokiol could be
      blocked by gene silencing or pharmacological agents. Both transforming growth
      factor (TGF)-beta1 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced cell
      migration, invasion and reciprocal down-regulation of epithelial marker E
      cadherin, which could be abrogated by siRNA-CRT. Moreover, Honokiol significantly
      suppressed MNNG-induced gastrointestinal tumor growth and over-expression of CRT
      in mice. Knockdown CRT in gastric cancer cells was found to effectively reduce
      growth ability and metastasis in vivo. The present study provides insight into
      the specific biological behavior of CRT in epithelial-to-mesenchymal transition
      (EMT) and metastasis. Taken together, our results suggest that the therapeutic
      inhibition of CRT by Honokiol suppresses both gastric tumor growth and peritoneal
      dissemination by dictating early translocation of CRT in immunogenic cell death,
      activating ER stress, and blocking EMT. 

PMID- 25619453
TI  - Evaluation of a preventive surgical site infection bundle in colorectal surgery.
AB  - OBJECTIVE: To assess the effectiveness of a protocol for prevention of surgical
      site infection (SSI) in colorectal surgery. PATIENTS AND METHODS: Evaluation of 2
      cohorts of patients undergoing colon and rectal surgery in a tertiary public
      hospital: A historical cohort (2008-2011) and a prospective one (after the
      implementation of the program in 2012). The main measures established were:
      Adequacy of preoperative antimicrobial prophylaxis, maintaining patient
      normothermia and appropriate glove change during the intervention. Comparability
      of the two cohorts was determined by a bivariate analysis of age, sex, NNIS
      index, ASA index, surgical time, perioperative transfusion, diagnosis, diabetes
      and renal failure. RESULTS: We assessed 342 patients (256 underwent colon surgery
      and 86 rectal surgery), divided into 2 cohorts: prior period (218), and post
      implementation period (124). The cumulative incidence of SSI in the first cohort
      was 27.5% (95% CI, 21.6- 33.4), and in the post-intervention cohort 16.9% (95%
      CI, 10.3-23.5, P=.03). Postoperative mortality was 9.2% (95% CI, 5.4-13) in the
      first cohort and 3.2% (95% CI, 0.1-6.3) in the post-intervention cohort (P=.04).
      The inadequacy of prophylaxis decreased from 37.4% (95% CI, 30.4-44.6) to 18.9%
      (95% CI, 11.9- 26.1) (P=.001). CONCLUSION: A significant decrease in the
      frequency of SSI, post-surgical mortality and inadequate antimicrobial
      prophylaxis is verified after the implementation of a protocol in colorectal
      surgery.

PMID- 25619454
TI  - Early drastic decrease in white blood count can predict uroseptic shock induced
      by upper urinary tract endoscopic lithotripsy: a translational study.
AB  - PURPOSE: Uroseptic shock is a life threatening complication after upper urinary
      tract endoscopic lithotripsy. Prompt diagnosis and treatment are paramount for
      patient survival. We identified a practical predictor of upper urinary tract
      endoscopic lithotripsy induced uroseptic shock in an animal model. We validated
      the results by retrospectively reviewing multicenter clinical records. MATERIALS
      AND METHODS: We ligated the rabbit ureter and injected Escherichia coli solution
      in the renal pelvis to create a uroseptic shock model. White blood count and
      other parameters were measured at different intervals and bacterial
      concentrations. Results were compared with clinical findings in 48 patients who
      experienced uroseptic shock after upper urinary tract endoscopic lithotripsy at a
      total of 8 medical centers. We used a ROC curve to evaluate the predictive value
      of parameters for uroseptic shock. RESULTS: We established a stable rabbit model
      by injecting 9.0 * 10(8) cfu/ml E. coli in the renal pelvis at a dose of 2 ml/kg.
      In patients and rabbits with uroseptic shock the white blood count decreased in
      the first 2 hours after the procedure. The ROC curve showed that the white blood
      count threshold within the first 2 hours of uroseptic shock was 2.85 * 10(9)/L.
      Sensitivity and specificity for predicting uroseptic shock were 95.9% and 92.7%,
      respectively. CONCLUSIONS: The white blood count decreased drastically within the
      first 2 hours during the development of uroseptic shock. This could be an ideal
      predictor of uroseptic shock after upper urinary tract endoscopic lithotripsy. In
      patients with high risk factors for uroseptic shock the white blood count should
      be measured within 2 hours after upper urinary tract endoscopic lithotripsy.

PMID- 25619455
TI  - Clear cell chondrosarcoma calcaneum - a case report and review of literature.
AB  - Chondrosarcoma is the second most common primary bone malignancy accounting for
      20-25% of all bone sarcomas. However chondrosarcoma of the foot is rare with just
      a handful of cases being described. Among the subtypes clear cell variant is the
      rarest and has never been documented in the foot. We present a rare case of clear
      cell chondrosarcoma of the calcaneum with multiple metastases that was treated at
      our institute. The patient was a 62-year old male who presented to us with pain
      and mass in the left hindfoot with difficulty in walking for 2 years and a
      discharging ulcer over the lateral aspect for 4 months. Radiography showed
      aggressive, destructive, lytic lesion in the calcaneum with cortical breach and
      soft tissue invasion. Bone scan and PET-CT revealed multiple bony metastases and
      lung metastasis. After initial biopsy, patient underwent below knee amputation
      and has been in remission since the last 18 months. Given the rarity of this
      tumor in the calcaneum, this report highlights the importance to consider the
      possibility of this tumor in the calcaneum as an early diagnosis; complete
      metastatic workup and expeditious management can thus significantly improve
      prognosis. 

PMID- 25619456
TI  - Multiple osteocartilaginous exostoses of the lower extremity: a case report.
AB  - An osteochrondoma is a benign osseous tumor capped by cartilage. Osteochondromas
      occurring at the distal tibia and fibula are uncommon and even more so when
      occurring at the first metatarsal head. Osteochondromas usually occur at the
      metaphysis of long bones; however, they can occur at other cortical bone
      metaphyses. This is a case report of a 54-year-old male with incidental
      radiographic findings of multiple osteochondromas around his ankles as well as a
      solitary osteochondromatous lesion growing proximally off the left first
      metatarsal head. The multiple osteochrondomas were evident on multiple views, and
      subsequent histological analysis of the solitary osteochondromatous lesion via
      total surgical excision confirmed a diagnosis of multiple hereditary
      osteochrondromatosis. 

PMID- 25619457
TI  - Bone marrow CD11b(+)F4/80(+) dendritic cells ameliorate collagen-induced
      arthritis through modulating the balance between Treg and Th17.
AB  - Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive
      function. In this study we determine the therapeutic effects and potential
      mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen
      induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated
      under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+)
      F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and
      indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to
      CIA mice by intravenous injections. The histopathology of joint and spleen were
      evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The
      expressions of Foxp3, Helios and RORgammat in T lymphocytes co-cultured with BM
      CD11b(+)F4/80(+) DCs were measured in vitro. We found that BM CD11b(+)F4/80(+)
      DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and
      IDO. BM CD11b(+)F4/80(+) DCs significantly reduced the pathologic scores in
      joints and spleens, which correlated significantly with the reduced T lymphocyte
      proliferation and Th17 cell number, and with the increased Tregs number. In
      vitro, OVA-pulsed BM CD11b(+)F4/80(+) DCs promoted Treg cell expansion, enhanced
      IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression,
      and inhibited RORgammat and IL-17 mRNA expression. Taken together, BM
      CD11b(+)F4/80(+) DCs are able to ameliorate the development and severity of CIA,
      at least partly by inducing Foxp3(+) Treg cell expansion and suppressing Th17
      function. The BM CD11b(+)F4/80(+) DCs might have a promising immunotherapeutic
      potential for autoimmune arthritis. 

PMID- 25619458
TI  - Ulcerative Colitis: What is the Optimal Treatment Goal and How Do We Achieve It?
AB  - OPINION STATEMENT: The treatment paradigms and therapeutic options for ulcerative
      colitis (UC) have rapidly evolved during the past decade. Traditionally, the
      treatment target has focused on achieving successful induction and maintenance of
      steroid-free clinical remission. This has been shown to provide a better quality
      of life and a reduction in complications, hospitalizations, and surgery. Recent
      studies, however, suggest that achieving "mucosal healing" or endoscopic
      remission may be the optimal treatment endpoint. In this review, we will examine
      the treatment goals for UC and the efficacy of each therapy to reach these
      targets. We will also review the therapeutic options available for UC:
      mesalamines, steroids, immunomodulators, and biologics, including the first anti
      integrin inhibitor, approved in May 2014, for the treatment of UC. Therapeutic
      drug monitoring, which measures serum drug level and anti-drug antibody
      concentrations, is emerging as an important clinical decision tool in patients on
      tumor necrosis factor (TNF)-antagonists. These evolving treatment strategies
      allow gastroenterologists to optimize control of the disease and offer patients a
      better quality of life.

PMID- 25619460
TI  - The cerebellum on cocaine: plasticity and metaplasticity.
AB  - Despite the fact that several data have supported the involvement of the
      cerebellum in the functional alterations observed after prolonged cocaine use,
      this brain structure has been traditionally ignored and excluded from the
      circuitry affected by addictive drugs. In the present study, we investigated the
      effects of a chronic cocaine treatment on molecular and structural plasticity in
      the cerebellum, including BDNF, D3 dopamine receptors, DeltaFosB, the Glu2 AMPA
      receptor subunit, structural modifications in Purkinje neurons and, finally, the
      evaluation of perineuronal nets (PNNs) in the projection neurons of the medial
      nucleus, the output of the cerebellar vermis. In the current experimental
      conditions in which repeated cocaine treatment was followed by a 1-week
      withdrawal period and a new cocaine challenge, our results showed that cocaine
      induced a large increase in cerebellar proBDNF levels and its expression in
      Purkinje neurons, with the mature BDNF expression remaining unchanged. Together
      with this, cocaine-treated mice exhibited a substantial enhancement of D3
      receptor levels. Both DeltaFosB and AMPA receptor Glu2 subunit expressions were
      enhanced in cocaine-treated animals. Significant pruning in Purkinje dendrite
      arborization and reduction in the size and density of Purkinje boutons contacting
      deep cerebellar projection neurons accompanied cocaine-dependent increase in
      proBDNF. Cocaine-associated effects point to the inhibitory Purkinje function
      impairment, as was evidenced by lower activity in these cells. Moreover, the
      probability of any remodelling in Purkinje synapses appears to be decreased due
      to an upregulation of extracellular matrix components in the PNNs surrounding the
      medial nuclear neurons. 

PMID- 25619459
TI  - Atf3 negatively regulates Ptgs2/Cox2 expression during acute inflammation.
AB  - By generating prostaglandins, cyclooxygenase-2 (Cox-2/Ptgs2) plays a critical
      role in regulating inflammatory responses. While several inflammatory stimuli
      have been shown to increase Ptgs2 expression, less is known about how the
      transcription of this gene is terminated. Here we show that stimulation of
      macrophages with yeast zymosan, a TLR2/6 and dectin-1 agonist, causes a transient
      increase in the expression of Ptgs2 accompanied by a simultaneous increase in the
      expression of the transcriptional repressor, activating transcription factor-3
      (Atf3). The expression of Ptgs2 was significantly higher in resident peritoneal
      macrophages isolated from Atf3(-/-) mice than that from Atf3(+/+) mice and was
      associated with higher prostaglandin production upon stimulation with zymosan. In
      activated macrophages, Atf3 accumulated in the nucleus and chromatin
      immunoprecipitation analysis showed that Atf3 is recruited to the Ptgs2 promoter
      region. In acute peritonitis and in cutaneous wounds, there was increased
      leukocyte accumulation and higher levels of prostaglandins (PGE2/PGD2) in
      inflammatory exudates of Atf3(-/-) mice compared with WT mice. Collectively,
      these results demonstrate that during acute inflammation Atf3 negatively
      regulates Ptgs2 and therefore dysregulation of this axis could potentially
      contribute to aberrant Ptgs2 expression in chronic inflammatory diseases.
      Moreover, this axis could be a new therapeutic target for suppressing Ptgs2
      expression and the resultant inflammatory responses. 

PMID- 25619461
TI  - Prognostic value of miR-106b expression in breast cancer patients.
AB  - BACKGROUND: The aim of the present study was to evaluate whether the level of
      expression of tissue or plasma miR-106b can be used to predict clinical outcomes
      in breast cancer patients. METHODS: Both tissue and plasma samples were collected
      and analyzed from 173 patients with primary breast cancer and a set of 50 women
      with fibroadenoma. The relative expression levels of miR-106b were determined
      using real-time quantitative reverse transcription polymerase chain reaction and
      in situ hybridization. RESULTS: The levels of miR-106b were upregulated in both
      tissue and plasma samples from breast cancer patients. The expression levels
      showed a linear correlation (rs = 0.748, P < 0.001) and were significantly
      correlated with tumor size, Ki67 expression, and lymph node metastasis (all P <
      0.05). Patients with high miR-106b expression levels tended to have shorter
      disease-free survival times and overall survival times (P < 0.001). In a Cox
      regression model, high-level tissue and plasma miR-106b expression were
      unfavorable prognostic factors, and receiver-operating characteristic analysis
      revealed that the tissue and plasma miR-106b levels provided considerable
      diagnostic accuracy, yielding an area under the ROC curve of 0.785 and 0.856,
      respectively. CONCLUSIONS: MiR-106b was found to be associated with a high risk
      of recurrence of breast cancer, and miR-106b is a putative plasma marker for risk
      assessment in patients with breast cancer.

PMID- 25619462
TI  - Impact of body mass index on perioperative outcomes and survival after resection
      for gastric cancer.
AB  - BACKGROUND: Among patients undergoing resection for gastric cancer, the impact of
      body mass index (BMI) on outcomes is not well understood. We sought to define the
      impact of non-normal BMI on short- and long-term outcomes after gastric cancer
      resection. METHODS: We identified 775 patients who underwent gastrectomy for
      adenocarcinoma between 2000 and 2012 from the multi-institutional US Gastric
      Cancer Collaborative. Clinicopathologic characteristics, operative details, and
      oncologic outcomes were collected, and patients were stratified according to BMI.
      RESULTS: Most patients in the cohort were classified as having normal BMI (n =
      338, 43.6%), followed by overweight (n = 229, 29.6%), obese (n = 153, 19.7%), and
      underweight (n = 55, 7.1%). After stratifying by BMI, there were no significant
      differences in the incidence of postoperative blood transfusions, perioperative
      morbidity, postoperative infectious complications, length of stay, perioperative
      30-d in-hospital death, or readmission across groups (all P > 0.05). BMI did not
      impact overall or recurrence-free survival after stratifying by stage (all P >
      0.05). However, underweight patients with low preoperative albumin levels had
      worse overall survival (OS) compared with that of patients of normal BMI.
      CONCLUSIONS: BMI did not impact perioperative morbidity, recurrence-free, or OS
      in patients undergoing gastric resection for adenocarcinoma. Underweight patients
      with BMI <18.5 kg/m(2) and low preoperative albumin levels, however, had a
      significantly decreased OS after gastrectomy for cancer. These high-risk patients
      should have their nutritional status optimized both before and after gastrectomy
      in an attempt to modify this risk factor and, in turn, achieve better outcomes.

PMID- 25619463
TI  - Electroacupuncture ST36 prevents postoperative intra-abdominal adhesions
      formation.
AB  - BACKGROUND: We have recently proved electroacupuncture (EA) ST36 exerted an anti
      inflammatory effect in the early phase of intra-abdominal adhesion formation.
      Evidences indicate that the anti-inflammatory effect of EA ST36 involves a
      cholinergic anti-inflammatory pathway-dependent mechanism via the vagus nerve.
      However, the exact effects and accurate vagal modulation of acupuncture in
      prevention of postoperative intra-abdominal adhesion formation has not been
      thoroughly evaluated. MATERIALS AND METHODS: Sprague-Dawley rats subjected to
      abdominal adhesion lesions operation at the cecum and abdominal wall were
      randomly divided into six groups as follows: (a) EAN: EA non-channel acupoints;
      (b) EA: EA ST36 after abdominal lesions; (c) VGX/EA: vagotomy (VGX) after
      abdominal lesions, then EA ST36; (d) VGX/EAN: VGX after abdominal lesions, then
      EAN; (e) alpha-BGT/EA: intraperitoneal injection of alpha-bungarotoxin (alpha
      BGT, an antagonist of alpha7 subunit of cholinergic nicotinic receptor) before EA
      ST36, and (f) alpha-BGT/EAN group: alpha-BGT injection before EAN. Seven days
      after abdominal surgical lesions, the levels of tumor necrosis factor-alpha (TNF
      alpha) and vascular endothelial growth factor (VEGF) in the adhesive tissue were
      evaluated, macroscopic observation and histopathologic evaluation of adhesion
      formation and assessment of angiogenesis by immunohistochemical staining of
      platelet endothelial cell adhesion molecule-1 (CD31) were performed. RESULTS: EA
      ST36 reduced TNF-alpha and VEGF levels in adhesive tissue homogenates 7 d after
      surgery, whereas vagotomy or intraperitoneal injection of alpha-BGT before EA
      ST36 reversed its suppressive effects. EA at non-channel acupoints with or
      without vagotomy or intraperitoneal injection of alpha-BGT before EA had no
      suppressive effects on TNF-alpha and VEGF levels. EA ST36 alleviated the adhesion
      formation, with both of macroscopic and histopathologic adhesion scores
      significantly lower than those of the EAN group (1.56 +/- 0.29 versus 3.00 +/-
      0.82, 1.35 +/- 0.4 versus 3.91 +/- 0.8, respectively, both P < 0.05). Compared
      with the EAN group, EA ST36 significantly decreased angiogenesis evidenced by
      reduced CD31 positive microvessel density in adhesive tissue. CONCLUSIONS: EA
      ST36 might reduce the postoperative local inflammatory response, attenuate the
      angiogenesis, and alleviate the adhesion formation partly via activating the
      cholinergic anti-inflammatory mechanism.

PMID- 25619464
TI  - Home electrical stimulation for women with fecal incontinence: a preliminary
      randomized controlled trial.
AB  - PURPOSE: The purpose of this study is to compare the effectiveness and cost of
      home electrical stimulation and standardized biofeedback training in females with
      fecal incontinence METHODS: Thirty-six females suffering from fecal incontinence
      were randomized into two groups, matched for mean age (67.45 +/- 7.2 years), mean
      body mass index (kg/m2) (26.2 +/- 3.9), mean disease duration (4.1 +/- 0.8
      years), mean number of births (2.7 +/- 1.3), and reports of obstetric trauma
      (25%). Questionnaires were used to evaluate their demographics, medical, and
      childbearing history. Subjects were randomized to home electrical stimulation or
      standardized biofeedback training for a period of 6 weeks. Subjective outcome
      measures included the frequency of fecal, urine, and gas incontinence by visual
      analog scale, Vaizey incontinence score, and subjects' levels of fecal
      incontinence related anxiety. Objective outcome measures included pelvic floor
      muscle strength assessed by surface electromyography. We also compared the cost
      of each treatment modality. RESULTS: Only females who received home electrical
      stimulation (HES) reported a significant improvement in Vaizey incontinence score
      (p = 0.001), anxiety (p = 0.046), and in frequency of leaked solid stool (p =
      0.013). A significant improvement in pelvic floor muscle strength was achieved by
      both groups. HES was much cheaper compared to the cost of standardized
      biofeedback training (SBT) (US $100 vs. US $220, respectively). Our study
      comprised a small female population, and the study endpoints did not include
      objective measures of anorectal function test, such as anorectal manometry,
      before and after treatment. CONCLUSIONS: Home electrical stimulation may offer an
      alternative to standardized biofeedback training as it is effective and generally
      well-tolerated therapy for females with fecal incontinence.

PMID- 25619465
TI  - Voice Problems in New Zealand Teachers: A National Survey.
AB  - OBJECTIVE: This study determined the prevalence and nature of voice problems in
      New Zealand (NZ) teachers using a national self-report questionnaire. STUDY
      DESIGN: Epidemiological cross-sectional survey. METHODS: Participants were 1879
      primary and secondary teachers (72.5% females). Three prevalence timeframes were
      estimated. Severity of voice problems, recovery time, days away from work,
      symptoms, health assistance, and voice education were also investigated. RESULTS:
      Prevalence of self-reported vocal problems was 33.2% during their teaching
      career, 24.7% over the teaching year, and 13.2% on the day of the survey. Primary
      teachers (P<0.001; odds ratio [OR]=1.74; confidence interval [CI]=1.33-2.40),
      females (P=0.008; OR=1.63; CI=1.13-2.37), and those aged 51-60 years (P=0.010;
      OR=1.45; CI=1.11-3.00) were more likely to report problems. Among teachers
      reporting voice problems during the year, 47% were moderate or severe; for 30%,
      voice recovery took more than 1 week. Approximately 28% stayed away from work 1-3
      days owing to a vocal problem and 9% for more than 3 days. Women reported longer
      recovery times and more days away. Symptoms associated with voice problems
      (P<0.001) were voice quality alteration (OR=4.35; CI=3.40-5.57), vocal effort
      (OR=1.15; CI=0.96-1.37), voice breaks (OR=1.55; CI=1.30-1.84), voice projection
      difficulty (OR=1.25; CI=1.04-1.50), and throat discomfort (OR=1.22; CI=1.02
      1.47). Of the teachers reporting voice problems, only 22.5% consulted a health
      practitioner. Only 38% of the teachers with chronic voice problems visited an
      otolaryngologist. Higher hours of voice training/education were associated with
      fewer self-reported voice problems. CONCLUSIONS: Voice problems are of concern
      for NZ teachers, as has been reported for teachers in other countries. There is
      still limited awareness among teachers about vocal health, potential risks, and
      specialized health services for voice problems.

PMID- 25619466
TI  - Parent and Child Responses to the Pediatric Voice-Related Quality-of-Life
      Questionnaire.
AB  - OBJECTIVES: When assessing pediatric dysphonia, there are different approaches
      that can be taken in gathering a subjective view of the impact voice difficulties
      have on a child. Most valid questionnaires require parent-proxy reporting,
      although it has become increasingly important to gather the views of children
      themselves. This study reports a pilot study of an adaptation to the Pediatric
      Voice-Related Quality-of-Life Questionnaire (PVRQoL). METHODS: A total of 24
      parent and child dyads were recruited from a tertiary pediatric voice clinic.
      Children were aged between 3 years and 8 months and 15 years and 3 months.
      Parents completed the existing PVRQoL questionnaire, whereas their children were
      given a child-adapted version. Follow-up completion of the child questionnaire
      was conducted after a 2-week period. RESULTS: There was a good correlation
      between the two time periods when children completed the adapted PVRQoL and also
      between parent and child responses. Of particular interest, however, was the
      different ratings on individual items by parents and their children with parents
      tending to overestimate the extent to which their children may be emotionally
      affected by their voice disorder. CONCLUSIONS: This study shows that children
      have much to tell about their own voice-related quality of life, so our
      conclusion is that they should also be self-assessed. The PVRQoL when adapted for
      use with children offers an additional insight that can be gathered in a
      relatively short timeframe and be considered with other assessments of vocal
      function.

PMID- 25619467
TI  - Aerodynamic measures and biofeedback as management in persistent paradoxical
      vocal fold motion and reverse phonation.
AB  - OBJECTIVES: Paradoxical vocal fold motion (PVFM) and reverse phonation are
      characterized by aberrant vocal fold adduction. To date, there have been no
      studies examining the aerodynamic events during reverse phonation. We present an
      unusual case of persistent reverse phonation secondary to respiratory distress
      associated with PVFM. STUDY DESIGN: Case report. METHODS: We present the case of
      a 42-year-old female with sudden onset of respiratory distress associated with
      PVFM and persistent reverse phonation. She underwent baseline aerodynamic
      measurements followed by trial therapy. Through the use of instrumental and
      tactile aerodynamic biofeedback, the patient was able to coordinate exhalatory
      breath pressure flow during phonation, which resulted in immediately improved
      voice quality from highly dysphonic to nearly normal voice quality. CONCLUSIONS:
      Patients with reverse phonation seldom undergo aerodynamic testing as part of the
      initial diagnostic and management program. Our case study demonstrates the
      effectiveness of aerodynamic technology to enable a patient with aberrant glottic
      function to recognize inspiratory phonation events and to reestablish consistent
      expiratory flow/pressure egress in speech tasks. Instrumental and tactile
      biofeedback is effective for reinforcement of normal flow patterns during speech
      tasks.

PMID- 25619468
TI  - The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant
      therapy in the treatment of recurrent respiratory papilloma.
AB  - OBJECTIVE: To examine the effect of the quadrivalent human papillomavirus
      vaccine, Gardasil, on the disease course of patients with recurrent respiratory
      papillomatosis (RRP). METHODS: A retrospective chart review of patients with RRP
      was conducted and 20 patients were selected who had received the Gardasil vaccine
      as part of their treatment. Efficacy was assessed by calculating the
      intersurgical interval (ISI) before and after receiving the vaccine, as well as
      number of complete and partial remissions. RESULTS: Analysis of all patients
      found a significant increase in the ISI of 3.1 months (95% confidence interval
      [CI]: 1.02-5.19, P=0.0061). Male patients experienced an increase in the ISI of
      4.2 months (95% CI: 1.6-6.7, P=0.0048). Female patients had a nonsignificant
      increase in ISI of 1.2 months (95% CI: 3.1-5.4, P=0.51). Eight patients (40%; six
      male and two female) experienced complete remission. Five patients (25%) overall
      (three male and two female) experienced partial remission. In total, complete or
      partial remission was achieved in a total of 13 (65%) patients (nine male and
      four female). CONCLUSIONS: The Gardasil vaccine can modulate the severity of RRP
      and induce remission in some patients. The effect was much greater in males and
      in females in low estrogen states.

PMID- 25619469
TI  - Characterizing liquid redistribution in a biphasic vibrating vocal fold using
      finite element analysis.
AB  - OBJECTIVES: Vocal fold tissue is biphasic and consists of a solid extracellular
      matrix skeleton swelled with interstitial fluid. Interactions between the liquid
      and solid impact the material properties and stress response of the tissue. The
      objective of this study was to model the movement of liquid during vocal fold
      vibration and to estimate the volume of liquid accumulation and stress
      experienced by the tissue near the anterior-posterior midline, where benign
      lesions are observed to form. METHODS: A three-dimensional biphasic finite
      element model of a single vocal fold was built to solve for the liquid velocity,
      pore pressure, and von Mises stress during and just after vibration using the
      commercial finite element software COMSOL Multiphysics (Version 4.3a, 2013,
      Structural Mechanics and Subsurface Flow Modules). Vibration was induced by
      applying direct load pressures to the subglottal and intraglottal surfaces.
      Pressure ranges, frequency, and material parameters were chosen based on those
      reported in the literature. Postprocessing included liquid velocity, pore
      pressure, and von Mises stress calculations as well as the frequency-stress and
      amplitude-stress relationships. RESULTS: Resulting time-averaged velocity vectors
      during vibration indicated liquid movement toward the midline of the fold, as
      well as upward movement in the inferior-superior direction. Pore pressure and von
      Misses stresses were higher in this region just after vibration. A linear
      relationship was found between the amplitude and pore pressure, whereas a
      nonlinear relationship was found between the frequency and pore pressure.
      CONCLUSIONS: Although this study had certain computational simplifications, it is
      the first biphasic finite element model to use a realistic geometry and
      demonstrate the ability to characterize liquid movement due to vibration. Results
      indicate that there is a significant amount of liquid that accumulates at the
      midline; however, the role of this accumulation still requires investigation.
      Further investigation of these mechanical factors may lend insight into the
      mechanism of benign lesion formation.

PMID- 25619470
TI  - The Safety of Antithrombotic Therapy During In-office Laryngeal Procedures-A
      Preliminary Study.
AB  - INTRODUCTION: In-office laryngeal procedures present an alternative to the risks
      and costs associated with general anesthesia. However, the inherent control
      afforded by the operative theater is decreased potentially increasing the risk of
      complications. Many patients undergoing these procedures have traditional
      surgical risk factors, such as antithrombotic (AT) medical therapy. We sought to
      quantify complication rates for in-office procedures as a function of AT therapy.
      METHODS: A retrospective review of 127 diverse, in-office laryngeal procedures
      was performed and patients were then stratified based on AT medication status and
      type of procedure. The primary dependent variables were intraoperative and
      postoperative complications. Additionally, in those patients undergoing
      procedures with the goal of voice improvement, Voice Handicap Index (VHI)-10
      scores were used to quantify the success of the procedure as a function of AT
      therapy. RESULTS: Of the 127 procedures, 27 procedures (21.2%) involved patients
      on some form of AT agent that was not ceased for the procedure. Across all
      patients, no intraoperative complications were encountered, irrespective of
      therapeutic status. Three postoperative complications were noted; all in patients
      not on AT therapy. A statistically significant improvement in VHI-10 scores was
      noted across all patients, irrespective of AT status. CONCLUSIONS: AT medications
      do not appear to increase the risk of complications associated with in-office
      laryngeal procedures. Furthermore, AT therapy seemed to have no negative impact
      on the voice outcomes of patients undergoing procedures for voice improvement.

PMID- 25619471
TI  - Integrating voice evaluation: correlation between acoustic and audio-perceptual
      measures.
AB  - OBJECTIVES/HYPOTHESIS: This article aims to establish correlations between
      acoustic and audio-perceptual measures using the GRBAS scale with respect to four
      different voice analysis software programs. STUDY DESIGN: Exploratory,
      transversal. METHODS: A total of 90 voice records were collected and analyzed
      with the Dr. Speech (Tiger Electronics, Seattle, WA), Multidimensional Voice
      Program (Kay Elemetrics, NJ, USA), PRAAT (University of Amsterdam, The
      Netherlands), and Voice Studio (Seegnal, Oporto, Portugal) software programs. The
      acoustic measures were correlated to the audio-perceptual parameters of the GRBAS
      and rated by 10 experts. RESULTS: The predictive value of the acoustic
      measurements related to the audio-perceptual parameters exhibited magnitudes
      ranging from weak (R(2)a=0.17) to moderate (R(2)a=0.71). The parameter exhibiting
      the highest correlation magnitude is B (Breathiness), whereas the weaker
      correlation magnitudes were found to be for A (Asthenia) and S (Strain). The
      acoustic measures with stronger predictive values were local Shimmer, harmonics
      to-noise ratio, APQ5 shimmer, and PPQ5 jitter, with different magnitudes for each
      one of the studied software programs. CONCLUSIONS: Some acoustic measures are
      pointed as significant predictors of GRBAS parameters, but they differ among
      software programs. B (Breathiness) was the parameter exhibiting the highest
      correlation magnitude.

PMID- 25619472
TI  - Quality of life in patients submitted to total laryngectomy.
AB  - BACKGROUND: Laryngeal carcinoma accounts for about 80 000 deaths annually
      worldwide. Despite its aggressiveness, total laryngectomy (TL) is a treatment
      option with curative intent. This article aims to evaluate its impact on these
      patients quality of life (QoL). MATERIAL AND METHODS: Thirty-four patients who
      underwent TL with bilateral neck dissection between 2003 and 2012 responded to
      the European Organization for Research and Treatment of Cancer QoL Core
      Questionnaire, the Self-Evaluation of Communication Experiences after Laryngeal
      Cancer Questionnaire, and the Hospital Anxiety and Depression Scale. RESULTS:
      Data revealed that QoL is lower in these patients compared with general
      population. Regarding alaryngeal speech modalities, esophageal speech is
      associated with a significantly higher physical functional capacity. CONCLUSIONS:
      TL results in a permanent disability with decreased functional capacity and
      psychological distress. Close monitoring of these patients and investing in
      speech rehabilitation are essential to preserve their QoL.

PMID- 25619473
TI  - Electroglottography in fasting subjects.
AB  - OBJECTIVE: To make a comparative analysis on the closed quotient (CQ) of the
      sustained vowel /e/ while fasting and nonfasting. STUDY DESIGN: Cross-sectional
      study. METHODS: A total of 20 male subjects were enrolled. The mean age was 30.45
      +/- 8.79 years with a range of 20-48 years. The mean weight while nonfasting was
      79.66 +/- 12.91 kg and while fasting was 78.51 +/- 12.70 kg. Demographic data
      included age, history of smoking, and weight. All subjects were evaluated while
      fasting and nonfasting. All subjects underwent laryngeal electroglottography
      while phonating the vowel /e/ at a comfortable pitch and loudness. The mean CQ,
      range, and standard deviations were computed while fasting and nonfasting. The
      degree of phonatory effort and vocal fatigue was also reported on a scale of 0-3.
      RESULTS: The difference in weight while fasting and nonfasting was statistically
      significant (P=0.001). There was no significant difference between the mean CQ
      while fasting versus nonfasting (44.49 +/- 1.15 and 44.30 +/- 1.41, P=0.94). The
      difference in the mean grade of phonatory effort was borderline significant
      (P=0.059) with 40% of the subjects having an increase in effort. With respect to
      vocal fatigue, there was an increase in the average while fasting by 0.25, which
      was statistically nonsignificant (P=0.109). CONCLUSIONS: The mean CQ during
      sustained /e/ is not affected by fasting. The presence of increased vocal effort
      and vocal fatigue could be secondary either to dehydration or respiratory muscle
      fatigue accompanying the weight loss.

PMID- 25619474
TI  - The Arg399Gln polymorphism in the XRCC1 gene is associated with increased risk of
      hematological malignancies.
AB  - The associations between the Arg399Gln polymorphism in X-ray repair cross
      complementing gene 1 (XRCC1) gene and the risk of hematological malignancies have
      been extensively investigated. However, the results were inconsistent. The
      objective of the current study is to investigate the association by meta
      analysis. We searched PubMed database, Embase database, CNKI database, Wanfang
      database, and Weipu database, covering all studies until August 7, 2013.
      Statistical analysis was performed by using the Revman4.2 software and the
      Stata10.0 software. A total of 27 case-control studies concerning the Arg399Gln
      polymorphism were included from 26 articles. The results suggested that the
      Arg399Gln polymorphism was not associated with an increased/decreased risk of
      hematological malignancies in total analysis (OR = 1.15, 95 % confidence interval
      (CI) = 0.97-1.35, P = 0.10 for Arg/Gln + Gln/Gln vs. Arg/Arg). In the subgroup
      analysis by ethnicity and cancer types, significant association was found in
      Asians (OR = 1.35, 95 % CI = 1.04-1.75, P = 0.03) but not in Europeans (OR =
      1.07, 95 % CI = 0.86-1.33, P = 0.56), and in leukemia (OR = 1.25, 95 % CI = 1.02
      1.54, P = 0.03) but not in lymphoma (OR = 0.98, 95 % CI = 0.80-1.20, P = 0.84) or
      myeloma (OR = 1.13, 95 % CI = 0.23-5.69, P = 0.88). The current meta-analysis
      indicated that the Arg399Gln polymorphism in the XRCC1 gene might be a risk
      factor for hematological malignancies in Asians or for leukemia. In future, more
      large-scale case-control studies are needed to validate these results.

PMID- 25619475
TI  - Overexpression of CUGBP1 is associated with the progression of non-small cell
      lung cancer.
AB  - The multifunctional RNA-binding protein CUGBP1 regulates multiple aspects of
      nuclear and cytoplasmic messenger RNA (mRNA) processing, including splicing,
      stabilization, and translation of mRNAs. Previous studies have shown that CUGBP1
      is overexpressed in non-small-cell lung cancer (NSCLC) tissues, but the
      pathological functions of CUGBP1 in tumorigenesis and development are unknown.
      Here, we provide the first evidence demonstrating the clinicopathological
      significance of CUGBP1 in NSCLC. Using immunohistochemistry, the levels of CUGBP1
      expression in NSCLC tissues and adjacent non-cancerous tissues were examined and
      determined to be associated with differentiation. Short hairpin RNA-induced
      downregulation of CUGBP1 promoted apoptosis and decreased proliferation in the
      A549 NSCLC cell line. Moreover, Western blot analysis indicated that the
      depletion of CUGBP1 increased the protein levels of cyclin D1, BAD, BAX, Jun D,
      and E-cadherin, while the cyclin B1 level decreased. Knockdown of CUGBP1
      decreased beta-catenin and vimentin levels and increased E-cadherin expression,
      suggesting that CUGBP1 may contribute significantly to epithelial to mesenchymal
      transition (EMT) progression. These results demonstrate the importance of CUGBP1
      in the biological and pathological functions of NSCLC and indicate its potential
      as a therapeutic target for NSCLC.

PMID- 25619476
TI  - Relation of glypican-3 and E-cadherin expressions to clinicopathological features
      and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.
AB  - Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate
      proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a
      tumor suppressor gene. Many studies had investigated E-cadherin expressions in
      colorectal carcinoma (CRC) while only one study had investigated GPC3 expression
      in CRC. This study aims to investigate expression of GCP3 and E-cadherin in
      colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using
      manual tissue microarray technique. Tumor tissue specimens are collected from 75
      cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to
      Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their
      clinicopathological parameters and survival data were revised and analyzed using
      established statistical methodologies. High-density manual tissue microarrays
      were constructed using modified mechanical pencil tip technique and
      immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher
      expression of GPC3 than MA with no statistically significant relation. NMA showed
      a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin
      positivity rates were significantly interrelated in NMA, but not in MA, group. In
      NMA group, there was no significant relation between either GPC3 or E-cadherin
      expression and the clinicopathological features. In a univariate analysis,
      neither GPC3 nor E-cadherin expression showed a significant impact on disease
      free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are
      not independent prognostic factors in CRC. However, expressions of both are
      significantly interrelated in NMA patients, suggesting an excellent interplay
      between both, in contrast to MA. Further molecular studies are needed to further
      explore the relationship between GCP3 and E-cadherin in colorectal
      carcinogenesis.

PMID- 25619477
TI  - Significantly inhibitory effects of low molecular weight heparin (Fraxiparine) on
      the motility of lung cancer cells and its related mechanism.
AB  - Low molecular weight heparin (LMWH) improving the cancer survival has been
      attracting attention for many years. Our previous study found that LMWH
      (Fraxiparine) strongly downregulated the invasive, migratory, and adhesive
      ability of human lung adenocarcinoma A549 cells. Here, we aimed to further
      identify the antitumor effects and possible mechanisms of Fraxiparine on A549
      cells and human highly metastatic lung cancer 95D cells. The ability of cell
      invasion, migration, and adhesion were measured by Transwell, Millicell, and MTT
      assays. FITC-labeled phalloidin was used to detect F-actin bundles in cells.
      Chemotactic migration was analyzed in a modified Transwell assay. Measurement of
      protein expression and phosphorylation activity of PI3K, Akt, and mTOR was
      performed with Western blot. Our studies found that Fraxiparine significantly
      inhibited the invasive, migratory, and adhesive characteristics of A549 and 95D
      cells after 24 h incubation and showed a dose-dependent manner. Fraxiparine
      influenced the actin cytoskeleton rearrangement of A549 and 95D cells by
      preventing F-actin polymerization. Moreover, Fraxiparine could significantly
      inhibit CXCL12-mediated chemotactic migration of A549 and 95D cells in a
      concentration-dependent manner. Furthermore, Fraxiparine might destroy the
      interaction between CXCL12-CXCR4 axis, then suppress the PI3K-Akt-mTOR signaling
      pathway in lung cancer cells. For the first time, our data indicated that
      Fraxiparine could significantly inhibit the motility of lung cancer cells by
      restraining the actin cytoskeleton reorganization, and its related mechanism
      might be through inhibiting PI3K-Akt-mTOR signaling pathway mediated by CXCL12
      CXCR4 axis. Therefore, Fraxiparine would be a potential drug for lung cancer
      metastasis therapy.

PMID- 25619478
TI  - miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1.
AB  - Accumulating evidence has shown that microRNAs are involved in multiple processes
      in cancer development and progression. Recent studies have shown that miR-23a
      functions as an oncogene in various human cancer types, but its role in
      osteosarcoma remains poorly understood. Here, we demonstrated that miR-23a is
      frequently downregulated in osteosarcoma specimens and cell lines compared with
      adjacent noncancerous tissues and cell line. Bioinformatics analysis further
      revealed SATB1 as a potential target of miR-23a. Data from luciferase reporter
      assays showed that miR-23a directly binds to the 3'UTR of SATB1 messenger RNA
      (mRNA). Furthermore, we found that expression patterns of miR-23a were inversely
      correlated with those of SATB1 in osteosarcoma tissues and cell lines, and
      overexpression of miR-23a suppressed SATB1 expression at both transcriptional and
      translational levels in osteosarcoma cell lines. In functional assays, miR-23a
      inhibited osteosarcoma cell proliferation, which could be reversed by
      overexpression of SATB1. Furthermore, knockdown of SATB1 reduced osteosarcoma
      cell proliferation, which resembled the inhibitory effects of miR-23a
      overexpression. Taken together, our data provide compelling evidence that miR-23a
      functions as a tumor suppressor in osteosarcoma, and its inhibitory effect on
      tumor are mediated chiefly through downregulation of SATB1.

PMID- 25619479
TI  - Finite element simulation of ultrasonic wave propagation in a dental implant for
      biomechanical stability assessment.
AB  - Dental implant stability, which is an important parameter for the surgical
      outcome, can now be assessed using quantitative ultrasound. However, the
      acoustical propagation in dental implants remains poorly understood. The
      objective of this numerical study was to understand the propagation phenomena of
      ultrasonic waves in cylindrically shaped prototype dental implants and to
      investigate the sensitivity of the ultrasonic response to the surrounding bone
      quantity and quality. The 10-MHz ultrasonic response of the implant was
      calculated using an axisymetric 3D finite element model, which was validated by
      comparison with results obtained experimentally and using a 2D finite difference
      numerical model. The results show that the implant ultrasonic response changes
      significantly when a liquid layer is located at the implant interface compared to
      the case of an interface fully bounded with bone tissue. A dedicated model based
      on experimental measurements was developed in order to account for the evolution
      of the bone biomechanical properties at the implant interface. The effect of a
      gradient of material properties on the implant ultrasonic response is determined.
      Based on the reproducibility of the measurement, the results indicate that the
      device should be sensitive to the effects of a healing duration of less than one
      week. In all cases, the amplitude of the implant response is shown to decrease
      when the dental implant primary and secondary stability increase, which is
      consistent with the experimental results. This study paves the way for the
      development of a quantitative ultrasound method to evaluate dental implant
      stability. 

PMID- 25619481
TI  - DEVELOPING A TECHNIQUE FOR ULTRASOUND-GUIDED INJECTION OF THE ADULT CANINE HIP.
AB  - An accurate method for guiding injections into the canine hip would facilitate
      diagnostic localization of lameness and targeted treatments. Ultrasound-guided
      hip injections are commonly used in humans and large animals. Aims of this
      prospective study were to describe ultrasound (US) anatomy of the adult canine
      hip and determine the feasibility and accuracy of intra-articular placement of
      injectate using US-guidance. Seven adult dogs were used to describe US anatomy,
      five dog cadavers were used to assess the feasibility of the injection technique
      and 11 dog cadavers were used to assess accuracy of injections. For the accuracy
      test, 22 joints were injected with iodinated contrast medium by three operators
      with different experience. With dogs in lateral recumbency, the hyperechoic
      femoral head surface was identified by following the femoral neck from the
      greater trochanter or the acetabular rim was localized by following caudally the
      ilium from the iliac wing. An anechoic gap between the femoral head and
      acetabular surface represented the joint. The capsule was visible as a triangular
      echoic structure and the femoral head articular cartilage appeared as an anechoic
      band. The needle was inserted axial to the greater trochanter and directed in a
      dorsolateral-ventromedial direction toward the joint space and then pushed
      through the capsule. Based on postinjection radiography, accuracy was 81.8% at
      first attempt and 100% at second attempt. This study indicated that US-guided
      injection is a feasible and accurate technique for injecting the adult canine
      hip. Future studies in live dogs are needed to assess safety and efficacy.

PMID- 25619482
TI  - Multipathogen real-time PCR system adds benefit for my patients: no.

PMID- 25619480
TI  - The role of gut microbiota in the development of type 1, type 2 diabetes mellitus
      and obesity.
AB  - Diabetes is a group of metabolic disorders characterized by persistent
      hyperglycemia and has become a major public health concern. Autoimmune type 1
      diabetes (T1D) and insulin resistant type 2 diabetes (T2D) are the two main
      types. A combination of genetic and environmental factors contributes to the
      development of these diseases. Gut microbiota have emerged recently as an
      essential player in the development of T1D, T2D and obesity. Altered gut
      microbiota have been strongly linked to disease in both rodent models and humans.
      Both classic 16S rRNA sequencing and shot-gun metagenomic pyrosequencing analysis
      have been successfully applied to explore the gut microbiota composition and
      functionality. This review focuses on the association between gut microbiota and
      diabetes and discusses the potential mechanisms by which gut microbiota regulate
      disease development in T1D, T2D and obesity. 

PMID- 25619483
TI  - What's new in post-ICU cognitive impairment?

PMID- 25619484
TI  - Multi-pathogen real-time PCR system adds benefit for my patients: yes.

PMID- 25619485
TI  - Comparison of different equations to assess glomerular filtration in critically
      ill patients.
AB  - PURPOSE: To evaluate equations for estimation of glomerular filtration rate (GFR)
      and measured urinary creatinine clearance, compared to measured GFR in critically
      ill patients. METHODS: GFR was measured using inulin clearance. Multiple blood
      samples were collected per patient for determination of serum creatinine,
      cystatin C and inulin. GFR was estimated by the use of the following estimation
      equations (eGFR): four commonly used creatinine-based equations [Cockcroft-Gault,
      Modification of Diet in Renal Disease (both the short and long formula) and
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)], five cystatin C
      based estimation equations (Hoek, Larsson, Filler, Le Bricon, CKD-EPIcys) and one
      equation combining cystatin C and serum creatinine (CKD-EPIcr-cys). In addition
      we measured urinary creatinine clearance. Bias, precision and accuracy of all
      estimates were compared to those of the inulin clearance. RESULTS: Data were
      collected from 83 patients, of whom 68 were considered evaluable. The median age
      was 58 years [interquartile range (IQR) 39-68]. The median inulin clearance was
      80 mL/min/1.73 m(2) (IQR 31-114). Equations based on creatinine had much bias and
      poor precision and accuracy. Measured urinary creatinine clearances overestimated
      GFR. Equations based on cystatin C were free of bias, but also had limited
      precision and accuracy. CONCLUSIONS: In this cohort of patients, estimates of GFR
      had low accuracy and precision. Cystatin C based formulas, especially CKD-EPIcr
      cys, showed limited bias; however, the accuracy and precision of these estimates
      were still insufficient. Measured urinary creatinine clearance overestimates GFR,
      but may provide a cheap alternative, when this is taken into account.

PMID- 25619486
TI  - Severe infections as the leading complication after the Lushan earthquake.

PMID- 25619487
TI  - Improving donor management and transplantation success: more research is needed.

PMID- 25619488
TI  - How to wean a patient from veno-arterial extracorporeal membrane oxygenation.

PMID- 25619489
TI  - Salvage of failed odontoid fixation through anterior C1/C2 transarticular screws.
AB  - Odontoid fracture fixation allows for early mobilisation out of orthosis. Both
      anterior and posterior fixation techniques have been described but anterior
      surgery has less post-operative morbidity through the use of natural cleavage
      planes. We described the use of anterior transarticular stabilisation as a
      salvage procedure following a failed odontoid screw fixation. 

PMID- 25619490
TI  - Acute Effects of Oral Tofisopam on Plasma Concentration and Urinary Excretion of
      Uric Acid and Oxypurinol "Preliminary Communication".
AB  - The effects of tofisopam, a GABA-receptor agonist, following oral administration
      (300mg) with and without allopurinol pretreatment on the plasma concentration and
      renal transport of uric acid and oxypurinol were investigated in 5 healthy
      subjects. Fractional and urinary excretions of uric acid were both significantly
      increased at 2-3 hours after tofisopam administration (559% and 459%,
      respectively), while plasma uric acid concentration was significantly decreased
      (36%) at 2.5 hours, suggesting that tofisopam affects uric acid metabolism via
      the tubular transport system. The hypouricemic effect of tofisopam was comparable
      to or greater than that of losartan and/or fenofibrate, which also have uric acid
      lowering activity. In addition, with prior administration of allopurinol, the
      fractional and urinary excretions of oxypurinol were increased at 2-3 hours after
      tofisopam administration (51% and 33%, respectively), while the plasma oxypurinol
      concentration was significantly decreased at 1.5 and 2.5 hours (15% and 21%,
      respectively). Accordingly, tofisopam may be an attractive compound for treatment
      of hyperuricemia and/or gout, especially in patients complicated with autonomic
      dysfunction symptoms, though it is possible that the uric acid-lowering effect of
      oxypurinol is attenuated by tofisopam.

PMID- 25619495
TI  - The sonographic features of malignant mediastinal lymph nodes and a proposal for
      an algorithmic approach for sampling during endobronchial ultrasound.
AB  - INTRODUCTION: There are several papers on the sonographic features of mediastinal
      lymph nodes affected by several diseases, but none gives the importance and
      clinical utility of the features. OBJECTIVE: In order to find out which lymph
      node should be sampled in a particular nodal station during endobronchial
      ultrasound, we investigated the diagnostic performances of certain sonographic
      features and proposed an algorithmic approach. METHODS: We retrospectively
      analyzed 1051 lymph nodes and randomly assigned them into a preliminary
      experimental and a secondary study group. The diagnostic performances of the
      sonographic features (gray scale, echogeneity, shape, size, margin, presence of
      necrosis, presence of calcification and absence of central hilar structure) were
      calculated, and an algorithm for lymph node sampling was obtained with decision
      tree analysis in the experimental group. Later, a modified algorithm was applied
      to the patients in the study group to give the accuracy. RESULTS: The demographic
      characteristics of the patients were not statistically significant between the
      primary and the secondary groups. All of the features were discriminative between
      malignant and benign diseases. The modified algorithm sensitivity, specificity,
      and positive and negative predictive values and diagnostic accuracy for detecting
      metastatic lymph nodes were 100%, 51.2%, 50.6%, 100% and 67.5%, respectively.
      CONCLUSIONS: In this retrospective analysis, the standardized sonographic
      classification system and the proposed algorithm performed well in choosing the
      node that should be sampled in a particular station during endobronchial
      ultrasound.

PMID- 25619494
TI  - Differences in IGF-axis protein expression and survival among multiethnic breast
      cancer patients.
AB  - There is limited knowledge about the biological basis of racial/ethnic
      disparities in breast cancer outcomes. Aberrations in IGF signaling induced by
      obesity and other factors may contribute to these disparities. This study
      examines the expression profiles of the insulin-like growth factor (IGF)-axis
      proteins and the association with breast cancer survival across a multiethnic
      population. We examined the expression profiles of the IGF1, IGF1R, IGFBP2 (IGF
      binding proteins), and IGFBP3 proteins in breast tumor tissue and their
      relationships with all-cause and breast cancer-specific survival up to 17 years
      postdiagnosis in a multiethnic series of 358 patients in Hawaii, USA. Native
      Hawaiians, Caucasians, and Japanese were compared. Covariates included
      demographic and clinical factors and ER/PR/HER2 (estrogen receptor/progesterone
      receptor/human epidermal growth factor receptor-2) status. In Native Hawaiian
      patients, IGFBP2 and IGFBP3 expression were each independently associated with
      overall and breast cancer mortality (IGFB2: HR(mort) = 10.96, 95% CI: 2.18-55.19
      and HR(mort) = 35.75, 95% CI: 3.64-350.95, respectively; IGFBP3: HR(mort) = 5.16,
      95% CI: 1.27-20.94 and HR(mort) = 8.60, 95% CI: 1.84-40.15, respectively). IGF1R
      expression was also positively associated with all-cause mortality in Native
      Hawaiians. No association of IGF-axis protein expression and survival was
      observed in Japanese or Caucasian patients. The interaction of race/ethnicity and
      IGFBP3 expression on mortality risk was significant. IGF-axis proteins may have
      variable influence on breast cancer progression across different racial/ethnic
      groups. Expression of binding proteins and receptors in breast tumors may
      influence survival in breast cancer patients by inducing aberrations in IGF
      signaling and/or through IGF-independent mechanisms. Additional studies to
      evaluate the role of the IGF-axis in breast cancer are critical to improve
      targeted breast cancer treatment strategies.

PMID- 25619496
TI  - Filling polymersomes with polymers by peroxidase-catalyzed atom transfer radical
      polymerization.
AB  - Polymersomes that encapsulate a hydrophilic polymer are prepared by conducting
      biocatalytic atom transfer radical polymerization (ATRP) in these hollow
      nanostructures. To this end, ATRPase horseradish peroxidase (HRP) is encapsulated
      into vesicles self-assembled from poly(dimethylsiloxane)-block-poly(2-methyl-2
      oxazoline) (PDMS-b-PMOXA) diblock copolymers. The vesicles are turned into
      nanoreactors by UV-induced permeabilization with a hydroxyalkyl phenone and used
      to polymerize poly(ethylene glycol) methyl ether acrylate (PEGA) by enzyme
      catalyzed ATRP. As the membrane of the polymersomes is only permeable for the
      reagents of ATRP but not for macromolecules, the polymerization occurs inside of
      the vesicles and fills the polymersomes with poly(PEGA), as evidenced by (1) H
      NMR. Dynamic and static light scattering show that the vesicles transform from
      hollow spheres to filled spheres during polymerization. Transmission electron
      microscopy (TEM) and cryo-TEM imaging reveal that the polymersomes are stable
      under the reaction conditions. The polymer-filled nanoreactors mimic the membrane
      and cytosol of cells and can be useful tools to study enzymatic behavior in
      crowded macromolecular environments. 

PMID- 25619497
TI  - Bilirubin provides perforator flap protection from ischaemia-reperfusion injury
      in a rat model: a preliminary result.
AB  - The use of bilirubin, a well-known and powerful antioxidant, has gained
      popularity in recent years because of its role in the prevention of ischaemic
      heart disease in patients with Gilbert's syndrome. We investigate the effects of
      bilirubin on ischaemia-reperfusion (I/R) injury using a rat perforator flap
      model. Forty-eight rats were randomly divided into two groups: experimental
      (bilirubin) group (n = 24) and control group (n = 24). In each group, elevated
      bilateral deep inferior epigastric perforator (DIEP) flaps were created. The
      right (no ischaemia side) and left (ischaemia side) DIEP flaps were separated
      according to the presence of ischaemia induction. Ischaemia was induced in
      anaesthetised rats by perforator clamping for 15 or 30 minutes. After surgery,
      the flap survival was assessed daily on postoperative days 0 to 5, and overall
      histological changes of DIEP flaps above the perforator were analysed at
      postoperative day 5. The flap survival rate in the bilirubin group was
      significantly higher than that in the control group at the ischaemia side
      following perforator clamping for 15 or 30 minutes (93.42 +/- 4.48% versus 89.63
      +/- 3.98%, P = 0.002; and 83.96 +/- 4.23% versus 36.46 +/- 6.38%, P < 0.001,
      respectively). The difference in flap survival between the two groups was the
      most prominent on the ischaemic side following 30 minutes of perforator clamping.
      From a morphologic perspective, pre-treatment with bilirubin was found to
      alleviate perforator flap necrosis caused by I/R injury in this experimental rat
      model. 

PMID- 25619498
TI  - Near-infrared excited ultraviolet emitting upconverting phosphors as an internal
      light source in dry chemistry test strips for glucose sensing.
AB  - Upconverting phosphors are inorganic crystals with interesting optical
      properties, including the ability to convert infrared radiation to emission at
      shorter wavelengths. In this paper we present the utilization of nanosized beta
      NaYF4:Yb(3+),Tm(3+), synthesized in the presence of K(+), emitting at 365 nm
      under 980 nm excitation as an internal light source in glucose sensing dry
      chemistry test strips. The feasibility of the nanoparticles as an internal UV
      light source was compared to the use of an external broadband lamp. The results
      obtained from glucose measurements using UCNPs were in agreement with the
      traditional method based on measuring reflectance using an external UV light
      source. In addition the multiple emission peaks of UCNPs offered the possibility
      of using them as a control signal to account for various sources of error arising
      in the assay. The high penetration depth of the NIR-excitation made it also
      possible to excite the UCNPs through a layer of whole blood, giving more freedom
      to the design of the optical setup. 

PMID- 25619499
TI  - Oncological outcome following anastomotic leak in rectal surgery.
AB  - BACKGROUND: The influence of anastomotic leak on local recurrence and survival
      remains debated in rectal cancer. METHODS: This was a multicentre observational
      study using data from the Spanish Rectal Cancer Project database. Demographics,
      American Society of Anesthesiologists classification, tumour location, stage, use
      of defunctioning stoma, administration of neoadjuvant and adjuvant treatment,
      invasion of circumferential resection margin, quality of mesorectal excision and
      anastomotic leakage were recorded. Anastomotic leak was defined as an anastomotic
      event requiring surgical intervention or interventional radiology, including
      pelvic abscesses without radiological evidence of leakage and early rectovaginal
      fistulas. Variables associated with oncological outcome were assessed by
      multivariable Cox regression analysis. RESULTS: A total of 1181 consecutive
      patients were included. Rates of anastomotic leak and 30-day postoperative
      mortality were 9.4 and 2.4 per cent respectively. Data from 1153 patients were
      analysed after a median follow-up of 5 years. Cumulative rates of local
      recurrence, overall recurrence, overall survival and cancer-specific survival
      were 4.9, 19.4, 77.5 and 84.7 per cent respectively. In the multivariable
      regression analysis, anastomotic leakage was not associated with local recurrence
      (hazard ratio (HR) 0.80, 95 per cent c.i. 0.28 to 2.26; P = 0.669), overall
      recurrence (HR 1.14, 0.70 to 1.85; P = 0.606), overall survival (HR 1.10, 0.73 to
      1.65; P = 0.648) or cancer-specific survival (HR 1.23, 0.75 to 2.02; P = 0.421).
      CONCLUSION: Anastomotic leak after low anterior resection did not affect
      oncological outcomes in these patients.

PMID- 25619500
TI  - Bisphenol A exposure induces metabolic disorders and enhances atherosclerosis in
      hyperlipidemic rabbits.
AB  - Bisphenol A (BPA) is an artificial environmental endocrine disrupter. Excess
      exposure to BPA may induce many disorders in the metabolism and cardiovascular
      system. However, the underlying toxicological mechanisms remain largely unknown.
      In this study, we administered genetically hyperlipidemic Watanabe heritable
      hyperlipidemic (WHHL-MI) rabbits (male, 14 week old), which have more common
      features with humans than the mouse and rat especially in the metabolism and
      cardiovascular system, with BPA at 40 mg kg(-1)  day(-1) for 8 weeks by gavage
      and compared their plasma lipids, glucose and insulin response with those of the
      vehicle group. All of the rabbits were sacrificed, and their pancreas, liver,
      adipose tissue, heart and aorta were analyzed using histological and morphometric
      methods. Furthermore, we treated human hepatoma HepG2 cells and human umbilical
      cord vein endothelial cells (HUVECs), with different doses of BPA based on the
      serum BPA levels in the WHHL rabbits for 6 h to investigate the possible
      molecular mechanisms. Our results showed that BPA-treated rabbits showed insulin
      resistance, prominent adipose accumulation and hepatic steatosis. Additionally,
      BPA exposure also caused myocardial injury and enhanced the development of
      atherosclerosis in the aortic arch with increased macrophage number (86%) and
      advanced lesion areas (69%). Increased expression of inflammatory genes found in
      the liver of BPA-treated rabbits along with the up-regulation of ER stress, lipid
      and glucose homeostasis and inflammatory genes in the cultured HepG2 cells and
      HUVECs suggest that BPA may induce metabolic disorders and enhance
      atherosclerosis through regulating above molecular pathways in the liver and
      endothelium.

PMID- 25619501
TI  - Therapeutic plasma exchange as treatment for propofol infusion syndrome.
AB  - Propofol infusion syndrome (PRIS), a rare complication of propofol sedation, is
      associated with high mortality. There is no specific therapy. A 16-year-old with
      head injury and status epilepticus is described. Three days after seizure
      resolution, whilst receiving propofol, he developed severe lactic acidosis,
      rhabdomyolysis, and hemodynamic instability. Suspected PRIS was treated with a
      single session of therapeutic plasma exchange (TPE). This was associated with
      immediate improvement in hemodynamic status, resolution of lactic acidosis within
      24 h, normalization of CPK over 10 days, and a subsequent full recovery. TPE is
      suggested as a novel therapy for PRIS.

PMID- 25619502
TI  - Shear-wave elastography and immunohistochemical profiles in invasive breast
      cancer: evaluation of maximum and mean elasticity values.
AB  - PURPOSE: To evaluate the correlations of maximum stiffness (Emax) and mean
      stiffness (Emean) of invasive carcinomas on shear-wave elastography (SWE) with
      St. Gallen consensus tumor phenotypes. METHODS: We used an ultrasound system with
      SWE capabilities to prospectively study 190 women with 216 histologically
      confirmed invasive breast cancers. We obtained one elastogram for each lesion. We
      correlated Emax and Emean with tumor size, histologic type and grade, estrogen
      and progesterone receptors, HER2 expression, the Ki67 proliferation index, and
      the five St. Gallen molecular subtypes: luminal A, luminal B without HER2
      overexpression (luminal B HER2-), luminal B with HER2 overexpression (luminal B
      HER2+), HER2, and triple negative. RESULTS: Lesions larger than 20 mm had
      significantly higher Emax (148.04 kPa) and Emean (118.32 kPa) (P=0.005) than
      smaller lesions. We found no statistically significant correlations between
      elasticity parameters and histologic type and grade or molecular subtypes,
      although tumors with HER2 overexpression regardless whether they expressed
      hormone receptors (luminal B HER2+ and HER2 phenotypes) and triple-negative
      tumors had lower Emax and Emean than the others. We assessed the B-mode
      ultrasound findings of the lesions with some of the Emax or Emean values less
      than or equal to 80 kPa; only four of these had ultrasound findings suggestive of
      a benign lesion (two with luminal A phenotype and two with HER2 phenotype).
      CONCLUSIONS: We were unable to demonstrate statistically significant differences
      among the subtypes of invasive tumors, although there appears to be a trend
      toward lower Emax and Emean in the aggressive phenotypes.

PMID- 25619503
TI  - Incremental value of secretin-enhanced magnetic resonance
      cholangiopancreatography in detecting ductal communication in a population with
      high prevalence of small pancreatic cysts.
AB  - PURPOSE: We investigated the incremental diagnostic yield of S-MRCP in a
      population with high prevalence of small pancreatic cysts. METHODS: Standard MRCP
      protocol was performed with and without secretin using 1.5 T units in subjects
      undergoing pancreatic screening because of a strong family history of pancreatic
      cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS
      3). All studies were reviewed prospectively by two independent readers who
      recorded the presence and number of pancreatic cysts, the presence of visualized
      ductal communication before and after secretin, and the degree of confidence in
      the diagnoses. RESULT: Of 202 individuals enrolled (mean age 56 years, 46%
      males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre
      and post-secretin MRCP images available for comparison. Data from the 128
      readings show that 6 (6/128=4.7%) had ductal communication visualized only on the
      secretin studies compared to pre-secretin studies (odds ratio 1.28, p=0.04). In
      addition, there was a statistically significant increase in confidence in
      reporting ductal communication after secretin compared to before secretin
      (p<0.0005). CONCLUSION: At 1.5 T MRI, the use of secretin can improve the
      visualization of ductal communication of cystic pancreatic lesions.

PMID- 25619504
TI  - A study of room-temperature LixMn1.5Ni0.5O4 solid solutions.
AB  - Understanding the kinetic implication of solid-solution vs. biphasic reaction
      pathways is critical for the development of advanced intercalation electrode
      materials. Yet this has been a long-standing challenge in materials science due
      to the elusive metastable nature of solid solution phases. The present study
      reports the synthesis, isolation, and characterization of room-temperature
      LixMn1.5Ni0.5O4 solid solutions. In situ XRD studies performed on pristine and
      chemically-delithiated, micron-sized single crystals reveal the thermal behavior
      of LixMn1.5Ni0.5O4 (0 <= x <= 1) cathode material consisting of three cubic
      phases: LiMn1.5Ni0.5O4 (Phase I), Li0.5Mn1.5Ni0.5O4 (Phase II) and Mn1.5Ni0.5O4
      (Phase III). A phase diagram capturing the structural changes as functions of
      both temperature and Li content was established. The work not only demonstrates
      the possibility of synthesizing alternative electrode materials that are
      metastable in nature, but also enables in-depth evaluation on the physical,
      electrochemical and kinetic properties of transient intermediate phases and their
      role in battery electrode performance. 

PMID- 25619506
TI  - alphabeta T cell receptors as predictors of health and disease.
AB  - The diversity of antigen receptors and the specificity it underlies are the
      hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes
      are indeed truly unique in their ability to generate receptors capable of
      recognizing virtually any pathogen. It has been known for several decades that T
      lymphocytes recognize short peptides derived from degraded proteins presented by
      major histocompatibility complex (MHC) molecules at the cell surface. Interaction
      between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both
      thymic selection and peripheral antigen recognition. It is widely assumed that
      TCR diversity is required, or at least highly desirable, to provide sufficient
      immune coverage. However, a number of immune responses are associated with the
      selection of predictable, narrow, or skewed repertoires and public TCR chains.
      Here, we summarize the current knowledge on the formation of the TCR repertoire
      and its maintenance in health and disease. We also outline the various molecular
      mechanisms that govern the composition of the pre-selection, naive and antigen
      specific TCR repertoires. Finally, we suggest that with the development of high
      throughput sequencing, common TCR 'signatures' raised against specific antigens
      could provide important diagnostic biomarkers and surrogate predictors of disease
      onset, progression and outcome.

PMID- 25619507
TI  - Emergence of neuronal diversity from patterning of telencephalic progenitors.
AB  - During central nervous system (CNS) development, hundreds of distinct neuronal
      subtypes are generated from a single layer of multipotent neuroepithelial
      progenitor cells. Within the rostral CNS, initial regionalization of the
      telencephalon marks the territories where the cerebral cortex and the basal
      ganglia originate. Subsequent refinement of the primary structures determines the
      formation of domains of differential gene expression, where distinct fate
      restricted progenitors are located. To understand how diversification of neural
      progenitors and neurons is achieved in the telencephalon, it is important to
      address early and late patterning events in this context. In particular,
      important questions include: How does the telencephalon become specified and
      regionalized along the major spatial axes? Within each region, are the
      differences in neuronal subtypes established at the progenitor level or at the
      postmitotic stage? If distinct progenitors exist that are committed to subtype
      specific neuronal lineages, how does the diversification emerge? What is the
      contribution of positional and temporal cues and how is this information
      integrated into the intrinsic programs of cell identity? WIREs For further
      resources related to this article, please visit the WIREs website.

PMID- 25619508
TI  - Young Chinese children's beliefs about the implications of subtypes of social
      withdrawal: A first look at social avoidance.
AB  - The goal of this study was to examine young Chinese children's beliefs about the
      implications of different subtypes of social withdrawal (e.g., shyness,
      unsociability), including for the first time, social avoidance. Participants were
      133 children in kindergarten (n = 58, Mage  = 70.85 months) and grade 1 (n = 75,
      Mage  = 83.49 months). Children were presented with vignettes describing
      hypothetical peers displaying shy, unsociable, avoidant, and socially competent
      behaviours and were then asked a series of questions to assess their beliefs
      about the implications of these different behaviours. Young children made
      distinctions between social withdrawal subtypes in terms of underlying
      motivations and emotions. Children also appeared to hold differential beliefs
      about the implications of different forms of social withdrawal: Of note, they
      anticipated that socially avoidant peers would experience the most negative
      outcomes. These findings provide some of the first evidence to suggest that
      social avoidance represents a distinct form of social withdrawal among young
      Chinese children. Results are discussed in terms of the importance of
      distinguishing between different subtypes of social withdrawal in Chinese
      culture. 

PMID- 25619510
TI  - Reply: A novel TUBB4A mutation suggests that genotype-phenotype correlation of H
      ABC syndrome needs to be revisited.

PMID- 25619509
TI  - White matter neuroanatomical differences in young children who stutter.
AB  - The ability to express thoughts through fluent speech production is a most human
      faculty, one that is often taken for granted. Stuttering, which disrupts the
      smooth flow of speech, affects 5% of preschool-age children and 1% of the general
      population, and can lead to significant communication difficulties and negative
      psychosocial consequences throughout one's lifetime. Despite the fact that
      symptom onset typically occurs during early childhood, few studies have yet
      examined the possible neural bases of developmental stuttering during childhood.
      Here we present a diffusion tensor imaging study that examined white matter
      measures reflecting neuroanatomical connectivity (fractional anisotropy) in 77
      children [40 controls (20 females), 37 who stutter (16 females)] between 3 and 10
      years of age. We asked whether previously reported anomalous white matter
      measures in adults and older children who stutter that were found primarily in
      major left hemisphere tracts (e.g. superior longitudinal fasciculus) are also
      present in younger children who stutter. All children exhibited normal speech,
      language, and cognitive development as assessed through a battery of assessments.
      The two groups were matched in chronological age and socioeconomic status. Voxel
      wise whole brain comparisons using tract-based spatial statistics and region of
      interest analyses of fractional anisotropy were conducted to examine white matter
      changes associated with stuttering status, age, sex, and stuttering severity.
      Children who stutter exhibited significantly reduced fractional anisotropy
      relative to controls in white matter tracts that interconnect auditory and motor
      structures, corpus callosum, and in tracts interconnecting cortical and
      subcortical areas. In contrast to control subjects, fractional anisotropy changes
      with age were either stagnant or showed dissociated development among major
      perisylvian brain areas in children who stutter. These results provide first
      glimpses into the neuroanatomical bases of early childhood stuttering, and
      possible white matter developmental changes that may lead to recovery versus
      persistent stuttering. The white matter changes point to possible structural
      connectivity deficits in children who stutter, in interrelated neural circuits
      that enable skilled movement control through efficient sensorimotor integration
      and timing of movements. 

PMID- 25619511
TI  - P-glycoprotein mediated drug interactions in animals and humans with cancer.
AB  - Drug-drug interactions can cause unanticipated patient morbidity and mortality.
      The consequences of drug-drug interactions can be especially severe when
      anticancer drugs are involved because of their narrow therapeutic index.
      Veterinary clinicians have traditionally been taught that drug-drug interactions
      result from alterations in drug metabolism, renal excretion or protein binding.
      More recently, drug-drug interactions resulting from inhibition of P-glycoprotein
      mediated drug transport have been identified in both human and veterinary
      patients. Many drugs commonly used in veterinary patients are capable of
      inhibiting P-glycoprotein function and thereby causing an interaction that
      results in severe chemotherapeutic drug toxicity. The intent of this review is to
      describe the mechanism and clinical implications of drug-drug interactions
      involving P-glycoprotein and anticancer drugs. Equipped with this information,
      veterinarians can prevent serious drug-drug interactions by selecting alternate
      drugs or adjusting the dose of interacting drugs. 

PMID- 25619512
TI  - Evaluation and diagnostic potential of serum ghrelin in feline hypersomatotropism
      and diabetes mellitus.
AB  - BACKGROUND: Ghrelin is a growth hormone secretagogue. It is a potent regulator of
      energy homeostasis. Ghrelin concentration is down-regulated in humans with
      hypersomatotropism (HS) and increases after successful treatment. Additionally,
      ghrelin secretion seems impaired in human diabetes mellitus (DM). HYPOTHESIS:
      Serum ghrelin concentration is down-regulated in cats with HS-induced DM (HSDM)
      compared to healthy control cats or cats with DM unrelated to HS and increases
      after radiotherapy. ANIMALS: Cats with DM (n = 20) and with HSDM (n = 32), 13 of
      which underwent radiotherapy (RT-group); age-matched controls (n = 20). METHODS:
      Retrospective cross-sectional study. Analytical performance of a serum total
      ghrelin ELISA was assessed and validated for use in cats. Differences in serum
      ghrelin, fructosamine, IGF-1 and insulin were evaluated. RESULTS: Ghrelin was
      significantly higher (P < .001) in control cats (mean +/- SD: 12.9 +/- 6.8 ng/mL)
      compared to HSDM- (7.9 +/- 3.3 ng/mL) and DM-cats (6.7 +/- 2.3 ng/mL), although
      not different between the HSDM- and DM-cats. After RT ghrelin increased
      significantly (P = .003) in HSDM-cats undergoing RT (from 6.6 +/- 1.9 ng/mL to
      9.0 +/- 2.2 ng/mL) and the after RT ghrelin concentrations of HSDM cats were no
      longer significantly different from the serum ghrelin concentration of control
      cats. Serum IGF-1 did not significantly change in HSDM-cats after RT, despite
      significant decreases in fructosamine and insulin dose. CONCLUSION AND CLINICAL
      IMPORTANCE: Ghrelin appears suppressed in cats with DM and HSDM, although
      increases after RT in HSDM, suggesting possible presence of a direct or indirect
      negative feedback system between growth hormone and ghrelin. Serum ghrelin might
      therefore represent a marker of treatment effect.

PMID- 25619513
TI  - Complication rates associated with transvenous pacemaker implantation in dogs
      with high-grade atrioventricular block performed during versus after normal
      business hours.
AB  - BACKGROUND: Transvenous pacemaker implantation in dogs is associated with a
      relatively high complication rate. At our institution, pacemaker implantation in
      dogs with high-grade atrioventricular block (HG-AVB) frequently is performed as
      an after-hours emergency. HYPOTHESIS: Among dogs with HG-AVB, the rate of major
      complications is higher when pacemakers are implanted after hours (AH) compared
      to during business hours (BH). ANIMALS: Client-owned dogs with HG-AVB that
      underwent transvenous pacemaker implantation between January 2002 and December
      2012 at the North Carolina State University Veterinary Teaching Hospital.
      METHODS: Retrospective medical record review. Two-year follow-up was required for
      complications analysis. RESULTS: Major complications occurred in 14/79 dogs (18%)
      and included lead dislodgement, lead or generator infection, lead or generator
      migration, and pacing failure. Incidence of major complications was significantly
      higher AH (10/36, 28%) compared to BH (4/43, 9%; P = .041), and all infectious
      complications occurred AH. Median survival time for all dogs was 27 months and
      did not differ between AH and BH groups for either all-cause (P = .70) or cardiac
      (P = .40) mortality. AH dogs were younger than BH dogs (P = .010), but there were
      no other clinically relevant differences between BH and AH groups in terms of
      demographic, clinical, or procedural variables. CONCLUSIONS AND CLINICAL
      IMPORTANCE: At our institution, AH transvenous pacemaker placement is associated
      with a higher rate of major complications (especially infections) compared to BH
      placement. This difference may be because of a variety of human factor
      differences AH versus BH.

PMID- 25619514
TI  - Serum cardiac troponin I concentrations in dogs with systemic inflammatory
      response syndrome.
AB  - BACKGROUND: Myocardial injury can be detected by cardiac troponin I (cTnI)
      concentration, which appears to be a predictor of short-term death in critically
      ill patients. It is unknown if the best prognostic indicator of short-term
      survival is cTnI measurement at admission or at later time points.
      HYPOTHESIS/OBJECTIVES: Measuring cTnI with a high-sensitivity (HS) test at
      different time points after admission may be a better short-term prognostic
      indicator than a single cTnI measurement at admission in dogs with systemic
      inflammatory response syndrome (SIRS). ANIMALS: Prospective, observational
      clinical study of 60 dogs with SIRS. METHODS: Cardiac troponin I concentration
      was measured in 133 serum samples, collected at days 1, 2, 3, and 5.
      Additionally, the acute patient physiologic and laboratory evaluation (APPLE)
      fast score was evaluated at admission. Prognostic capabilities of cTnI
      measurement and APPLE fast score for 28-day mortality were assessed by receiver
      operating characteristic curve analysis. RESULTS: Forty-one dogs with SIRS that
      survived 28 days had significantly lower serum cTnI concentrations at admission
      (median, 0.09 ng/mL; P = .004) and at the peak time point (median, 0.23 ng/mL; P
      = .01) compared to 19 nonsurvivors (median at admission, 0.63 ng/mL; median at
      peak, 1.22 ng/mL). Area under the curve to predict survival, using cTnI was
      similar at admission (0.732) and at peak (0.708), and was 0.754 for the APPLE
      fast score. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased cTnI concentration in
      dogs with SIRS is associated with poor outcome. Daily follow-up measurement of
      cTnI concentration provides no additional prognostic information for short-term
      mortality.

PMID- 25619515
TI  - Treatment of ionized hypercalcemia in 12 cats (2006-2008) using PO-administered
      alendronate.
AB  - BACKGROUND: Long-term treatment of cats with ionized hypercalcemia using
      alendronate has not been evaluated. HYPOTHESIS/OBJECTIVES: Alendronate is well
      tolerated in treatment of ionized hypercalcemia in cats. ANIMALS: A total of 12
      cats with ionized hypercalcemia. METHODS: Prospective study of 12 cats with
      ionized hypercalcemia of idiopathic origin was identified by telephone and email
      communication with a convenience sample of consulting veterinarians. Cats were
      treated with alendronate at a dose of 5-20 mg per feline PO q7d. Serum ionized
      calcium concentration (iCa) was measured before beginning treatment with
      alendronate, and after 1, 3, and 6 months of treatment. Alendronate dosage was
      adjusted according to iCa. Evaluation included physical examination, CBC,
      biochemistry profile, and diagnostic imaging. The owners and referring
      veterinarians were questioned about any observed adverse effects. The Wilcoxon
      matched-pairs signed rank test was used to compare baseline iCa to iCa at
      different time periods. RESULTS: Alendronate treatment resulted in a decrease in
      iCa in all 12 cats. The median percentage change in iCa was -13.2%, -15.9%, and 
      18.1% (range, -29.6 to +7.6; -30.5 to -1.9; -45.8 to +1.5%) at the 1, 3, and 6
      month time points, respectively. Baseline iCa was significantly different from 1
      month (P = .0042), 3 months (P = .0005), and 6 months (P = .0015). No adverse
      effects were reported for any of the cats. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Alendronate was well tolerated and decreased iCa in most cats for the 6-month
      period of observation.

PMID- 25619516
TI  - Insulin-like growth factor--phosphatidylinositol 3 kinase signaling in canine
      cortisol-secreting adrenocortical tumors.
AB  - BACKGROUND: Hypercortisolism is a common endocrine disorder in dogs, caused by a
      cortisol-secreting adrenocortical tumor (AT) in approximately 15% of cases. In
      adrenocortical carcinomas of humans, activation of the phosphatidylinositol 3
      kinase (PI3K) signaling pathway by insulin-like growth factor (IGF) signaling
      represents a promising therapeutic target. OBJECTIVES: To investigate the
      involvement of PI3K signaling in the pathogenesis of ATs in dogs and to identify
      pathway components that may hold promise as future therapeutic targets or as
      prognostic markers. ANIMALS: Analyses were performed on 36 canine cortisol
      secreting ATs (11 adenomas and 25 carcinomas) and 15 normal adrenal glands of
      dogs. METHODS: mRNA expression analysis was performed for PI3K target genes, PI3K
      inhibitor phosphatase and tensin homolog (PTEN), IGFs, IGF receptors, IGF binding
      proteins and epidermal growth factor receptors. Mutation analysis was performed
      on genes encoding PTEN and PI3K catalytic subunit (PIK3CA). RESULTS: Target gene
      expression indicated PI3K activation in carcinomas, but not in adenomas. No amino
      acid-changing mutations were detected in PTEN or PIK3CA and no significant
      alterations in IGF-II or IGFR1 expression were detected. In carcinomas, ERBB2
      expression tended to be higher than in normal adrenal glands, and higher
      expression of inhibitor of differentiation 1 and 2 (ID1 and ID2) was detected in
      carcinomas with recurrence within 2.5 years after adrenalectomy. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Based on these results, ERBB2 might be a promising
      therapeutic target in ATs in dogs, whereas ID1 and 2 might be valuable as
      prognostic markers and therapeutic targets.

PMID- 25619517
TI  - Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with
      surgically resected extraparenchymal spinal cord hematomas.
AB  - BACKGROUND: Extraparenchymal spinal cord hematoma has been described in
      veterinary medicine in association with neoplasia, intervertebral disk disease,
      and snake envenomation. There are rare reports of spontaneous extraparenchymal
      spinal cord hematoma formation with no known cause in human medicine. Multiple
      cases of spontaneous extraparenchymal spinal cord hematoma have not been
      described previously in veterinary medicine. OBJECTIVES: To describe the
      signalment, clinical findings, magnetic resonance imaging (MRI) features, and
      surgical outcomes in histopathologically confirmed extraparenchymal spinal cord
      hematomas in dogs with no identified underlying etiology. ANIMALS: Six dogs had
      MRI of the spinal cord, decompressive spinal surgery, and histopathologic
      confirmation of extraparenchymal spinal cord hematoma not associated with an
      underlying cause. METHODS: Multi-institutional retrospective study. RESULTS: Six
      patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI
      showed normal signal within the spinal cord parenchyma in all patients. All
      hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast
      enhancement. All dogs underwent surgical decompression and most patients (5/6)
      returned to normal or near normal neurologic function postoperatively. Follow-up
      of the patients (ranging between 921 and 1,446 days) showed no progression of
      neurologic clinical signs or any conditions associated with increased bleeding
      tendency. CONCLUSIONS AND CLINICAL IMPORTANCE: Before surgery and histopathology
      confirming extraparenchymal hematoma, the primary differential in most cases was
      neoplasia, based on the MRI findings. This retrospective study reminds clinicians
      of the importance of the combination of advanced imaging combined with
      histopathologic diagnosis. The prognosis for spontaneous spinal cord
      extraparenchymal hematoma with surgical decompression appears to be favorable in
      most cases.

PMID- 25619518
TI  - Randomized phase III trial of piroxicam in combination with mitoxantrone or
      carboplatin for first-line treatment of urogenital tract transitional cell
      carcinoma in dogs.
AB  - BACKGROUND: Reported response rates of transitional cell carcinoma (TCC) in dogs
      to piroxicam in combination with either mitoxantrone or carboplatin are similar;
      however, it is unknown whether either drug might provide superior duration of
      response. HYPOTHESIS/OBJECTIVES: To determine if the progression-free interval
      (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than
      that of dogs receiving carboplatin and piroxicam. The hypothesis was that the
      efficacy of mitoxantrone is no different from carboplatin. ANIMALS: Fifty dogs
      with TCC without azotemia. METHODS: Prospective open-label phase III randomized
      study. Either mitoxantrone or carboplatin was administered every 3 weeks
      concurrently with piroxicam with restaging at 6-week intervals. Twenty-four dogs
      received carboplatin and 26 received mitoxantrone. RESULTS: Response was not
      different between groups (P = .56). None of the dogs showed complete response. In
      the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%)
      dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%)
      and 13 (54%) dogs with SD. The PFI was not significantly different between groups
      (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86;
      95% confidence interval 0.47-1.56). Dogs with prostatic involvement experienced a
      shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or
      apically located tumors; this difference was significant (median 300, 190, and
      645 days, respectively; P = .005). CONCLUSIONS AND CLINICAL IMPORTANCE: This
      study did not detect a different in outcome in dogs with TCC treated with either
      mitoxantrone or carboplatin in combination with piroxicam.

PMID- 25619519
TI  - Effect of synthetic colloid administration on coagulation in healthy dogs and
      dogs with systemic inflammation.
AB  - BACKGROUND: Synthetic colloids are often used during fluid resuscitation and
      affect coagulation. OBJECTIVE: To compare the effects of an isotonic crystalloid
      and synthetic colloid on coagulation in healthy dogs and dogs with systemic
      inflammation. ANIMALS: Sixteen adult purpose-bred Beagles. METHODS: Randomized,
      placebo-controlled, blinded study. Dogs were randomized into one of two groups
      receiving fluid resuscitation with either 40 mL/kg IV 0.9% NaCl or tetrastarch
      after administration of lipopolysaccharide or an equal volume of placebo. After a
      14-day washout period, the study was repeated such that dogs received the
      opposite treatment (LPS or placebo) but the same resuscitation fluid. Blood
      samples were collected at 0, 1, 2, 4, and 24 hours for measurement of coagulation
      variables. RESULTS: Administration of either fluid to healthy dogs and dogs with
      systemic inflammation resulted in similar increases in prothrombin time and
      activated clotting time. In comparison to saline administration, tetrastarch
      administration resulted in significantly decreased R (P = .017) in healthy dogs,
      as well as significantly increased activated partial thromboplastin time (P <=
      .016), CL30% (P <= .016), and K (P < .001) and significantly decreased platelet
      count (P = .019), alpha (P <= .001), MA (P < .001), and von Willebrand factor
      antigen (P < .001) and collagen binding activity (P <= .003) in both healthy dogs
      and dogs with systemic inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Tetrastarch bolus administration to dogs with systemic inflammation resulted in a
      transient hypocoagulability characterized by a prolonged activated partial
      thromboplastin time, decreased clot formation speed and clot strength, and
      acquired type 1 von Willebrand disease.

PMID- 25619520
TI  - Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.
AB  - BACKGROUND: Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of
      the most common allergic diseases in horses in the northern hemisphere.
      Hypersensitivity reactions to environmental antigens cause an allergic
      inflammatory response in the equine airways. Cytosine-phosphate-guanosine
      oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a
      Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin
      nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug
      delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary
      studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown
      promising results. OBJECTIVES: The aim of this study was to evaluate the clinical
      and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo
      controlled, prospective, randomized clinical trial and to verify a sustained
      effect post-treatment. ANIMALS AND METHODS: Twenty-four RAO-affected horses
      received 1 inhalation every 2 days for 5 consecutive administrations. Horses were
      examined for clinical, endoscopic, cytological, and blood biochemical variables
      before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post
      treatment (III). RESULTS: At time points I and II, administration of treatment
      rather than placebo corresponded to a statistically significant decrease in
      respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and
      neutrophil percentage, and an increase in arterial oxygen pressure. CONCLUSION
      AND CLINICAL IMPORTANCE: Administration of a GNP-bound CpG-ODN formulation caused
      a potent and persistent effect on allergic and inflammatory-induced clinical
      variables in RAO-affected horses. This treatment, therefore, provides an
      innovative, promising, and well-tolerated strategy beyond conventional
      symptomatic long-term therapy and could serve as a model for asthma treatment in
      humans.

PMID- 25619521
TI  - Efficacy of gamithromycin for the treatment of foals with mild to moderate
      bronchopneumonia.
AB  - BACKGROUND: Gamithromycin is active in vitro against the bacterial agents most
      commonly associated with bronchopneumonia in older foals. However, the clinical
      efficacy and safety of this drug have not been investigated. HYPOTHESIS:
      Gamithromycin is effective for the treatment of bronchopneumonia in foals.
      ANIMALS: One hundred and twenty-one foals on a farm endemic for infections caused
      by Rhodococcus equi. METHODS: In a controlled, randomized, and double blinded
      clinical trial, foals with ultrasonographic evidence of pulmonary abscesses
      (abscess score 8.0-20 cm) were randomly allocated in 3 treatment groups: (1)
      gamithromycin IM q7 days (n = 40); (2) azithromycin with rifampin, PO q24h (n =
      40); or (3) no antimicrobial treatment (controls; n = 41). Physical examination
      and thoracic ultrasonography were performed by individuals unaware of treatment
      group assignment. Foals that worsened were removed from the study. RESULTS: The
      proportion of foals that recovered without the need to be removed from the study
      was significantly higher for foals treated with gamithromycin (38 of 40) or
      azithromycin with rifampin (39 of 40) than for controls (32 of 41). Treatment
      with gamithromycin or with azithromycin-rifampin resulted in a significantly
      faster decrease in the clinical score and abscess score compared to the controls.
      Adverse reactions characterized by colic (n = 18) and hind limb lameness (n = 14)
      were observed only in foals treated with gamithromycin. CONCLUSION AND CLINICAL
      IMPORTANCE: Gamithromycin was noninferior to azithromycin with rifampin for the
      treatment of bronchopneumonia in the study population but had a higher frequency
      of adverse reactions.

PMID- 25619522
TI  - Cardiac troponin I as compared to troponin T for the detection of myocardial
      damage in horses.
AB  - BACKGROUND: Different cardiac troponin I (cTnI) assays give different results.
      Only 1 manufacturer has marketed troponin T (cTnT) assays. Therefore, cTnT often
      is preferred for detection of myocardial infarction in human patients. Studies of
      cTnT in horses are limited. OBJECTIVES: To compare a cTnI and a high-sensitive
      cTnT assay (hs-cTnT) in horses. ANIMALS: Cardiac troponin I and cTnT were
      determined in 35 healthy horses (group 1), 23 horses suspected to have primary
      myocardial damage (group 2a), and 41 horses with secondary myocardial damage
      caused by structural heart disease (group 2b). METHODS: All cTnI samples were
      analyzed at laboratory A (limit of detection [LOD]: 0.03 ng/mL), whereas cTnT
      samples were analyzed at 2 laboratories with the same hs-cTnT assay (laboratory
      B, LOD: 10.0 pg/mL; laboratory C, LOD: 4.0 pg/mL). RESULTS: The median cTnI
      concentration in group 2a (0.90 ng/mL; range, 0.03-58.27 ng/mL) was significantly
      higher (P < .001) than in group 1 (0.03 ng/mL; range, 0.03-0.09 ng/mL) or group
      2b (0.05 ng/mL; range, 0.03-30.92 ng/mL), and the optimal cut-off for detection
      of primary myocardial damage was 0.095 ng/mL (sensitivity: 90.5%, specificity:
      100%). Using an LOD of 10.0 pg/mL for all cTnT samples, a cut-off value of 10.5
      pg/mL was found, but sensitivity was low (42.9%). When only samples analyzed at
      laboratory C (n = 58) were included, a cut-off of 6.6 pg/mL was found
      (sensitivity: 81%, specificity: 100%). CONCLUSIONS AND CLINICAL IMPORTANCE:
      Despite large quantitative differences, cTnI and cTnT are both useful for
      detection of myocardial damage in horses.

PMID- 25619523
TI  - Brainstem auditory evoked responses in foals: reference values, effect of age,
      rate of acoustic stimulation, and neurologic deficits.
AB  - BACKGROUND: Age and rate of acoustic stimulation affect peak latencies in
      brainstem auditory evoked responses (BAER) in humans. Those effects are unknown
      in foals. HYPOTHESIS/OBJECTIVES: Our goals were to (1) establish reference values
      for BAER in foals by using 3 different stimulation protocols, (2) evaluate the
      effects of age and stimulation frequencies on BAER tracing in foals up to 6
      months old, and (3) compare the data with BAER obtained from foals with central
      nervous system (CNS) disorders. ANIMALS: Thirty-nine neurologically normal foals
      and 16 foals with neurologic diseases. METHODS: Prospective observational
      clinical study. BAER recorded by using 3 protocols of stimulation (11.33
      repetitions per second [Hz]/70 decibel normal hearing level [dBNHL]; 11.33 Hz/90
      dBNHL; 90 Hz/70 dBNHL). RESULTS: No effect of age was observed in normal foals (P
      > .005). No significant difference was observed for latencies and interpeak
      latencies (IPL) when comparing foals with neurologic diseases and normal foals (P
      > .05), but 78.6% of foals with neurologic diseases had an asymmetry in their
      tracing, reflecting a difference in conduction time between the left and right
      side of the brainstem. Increasing the stimulation rate did not improve detection
      of CNS disorders. CONCLUSIONS AND CLINICAL IMPORTANCE: We propose BAER reference
      values for foals up to 6 months of age by using 3 protocols. Most foals with
      neurologic deficits had abnormal BAER tracing.

PMID- 25619524
TI  - Respiratory pathogens in Quebec dairy calves and their relationship with clinical
      status, lung consolidation, and average daily gain.
AB  - BACKGROUND: Bovine respiratory disease (BRD) is 1 of the 2 most important causes
      of morbidity and mortality in dairy calves. Surprisingly, field data are scant
      concerning the prevalence of respiratory pathogens involved in BRD in preweaned
      dairy calves, especially in small herds. OBJECTIVES: To identify the main
      respiratory pathogens isolated from calves in Quebec dairy herds with a high
      incidence of BRD, and to determine if there is an association between the
      presence of these pathogens and clinical signs of pneumonia, lung consolidation,
      or average daily gain. ANIMALS: Cross-sectional study using a convenience sample
      of 95 preweaned dairy calves from 11 dairy herds. METHODS: At enrollment, calves
      were weighed, clinically examined, swabbed (nasal and nasopharyngeal), and lung
      ultrasonography was performed. One month later, all calves were reweighed.
      RESULTS: Twenty-two calves had clinical BRD and 49 had ultrasonographic evidence
      of lung consolidation. Pasteurella multocida, Mannheimia haemolytica, and
      Histophilus somni were isolated in 54, 17, and 12 calves, respectively.
      Mycoplasma bovis was identified by PCR testing or culture in 19 calves, and 78
      calves were found to be positive for Mycoplasma spp. Bovine coronavirus was
      detected in 38 calves and bovine respiratory syncytial virus in 1. Only the
      presence of M. bovis was associated with higher odds of clinical signs, lung
      consolidation, and lower average daily gain. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Results suggested that nasopharyngeal carriage of M. bovis was detrimental to
      health and growth of dairy calves in small herds with a high incidence of BRD.

PMID- 25619525
TI  - Reliability of the i-STAT for the determination of blood electrolyte (K+, Na+,
      and CI-) concentrations in cattle.
AB  - BACKGROUND: Rapid determination of blood electrolyte concentrations can help
      determine electrolyte status and delivery of effective volume of electrolyte
      solutions in field conditions. OBJECTIVE: To evaluate reliability of the i-STAT,
      a point-of-care (POC) device, in measuring blood K(+), Na(+), and CI(-)
      concentrations in cattle. ANIMALS: Ninety-eight cattle with various diseases.
      METHODS: In this prospective study, blood samples collected from the jugular vein
      were processed for determination of K(+), Na(+), and CI(-) concentrations in
      blood and plasma using the i-STAT and auto-analyzer (Cobas C501), respectively.
      Blood and plasma electrolyte data were subjected to student t-test for
      comparison, the concordance analysis for agreement, accuracy, and precision, the
      Passing-Bablok regression and the Bland-Altman plot for reliability, and receiver
      operating characteristics curves for sensitivity (Se) and specificity (Sp).
      RESULTS: Plasma concentrations of K(+) (4.39 versus 4.2 mmol/L; P < .0001) and
      CI(-) (100.30 versus 99.4 mmol/L; P < .04) were greater than their concentrations
      in blood. Plasma and blood Na(+) concentrations were similar (136.95 versus 136.8
      mmol/L). The i-STAT results were highly correlated with the Cobas C501 results (r
      = 0.970, 0.922, and 0.866 for K(+), Na(+), and CI(-), respectively). Regression
      equations fitting blood (Y) and plasma (X) concentration did not deviate from the
      identity line for K(+) (Y = -0.10 + 0.98 * X), Na(+) (Y = X), and CI(-) (Y = 3.04
      + 0.96 * X). The mean bias (blood concentration - plasma concentration) was -0.20
      for K(+) (P = .03), -0.16 for Na(+) (P = .12), and -0.87 for CI(-) (P = .93). The
      i-STAT had 76-100% Se and 87.7-100% Sp for assessing electrolyte statuses.
      CONCLUSIONS AND CLINICAL IMPORTANCE: The i-STAT yielded results that were in
      agreement with the auto-analyzer, with negligible biases in measurement of plasma
      K(+), Na(+), and CI(-) concentrations. The i-STAT is a reliable POC device and
      can be used in field condition to assess electrolyte status in cattle.

PMID- 25619526
TI  - Apparent resolution of canine primary hypoparathyroidism with immunosuppressive
      treatment.

PMID- 25619527
TI  - Hemolytic anemia in horses associated with ingestion of Pistacia leaves.

PMID- 25619528
TI  - Synergistic binding of the leader and core peptides by the lantibiotic synthetase
      HalM2.
AB  - Lanthipeptides are a class of ribosomally produced and post-translationally
      modified peptides (RiPPs) that possess a variety of biological activities but
      typically act as antimicrobial agents (lantibiotics). Haloduracin is a
      lantibiotic that is composed of two post-translationally modified peptides,
      Halalpha and Halbeta, which are biosynthesized from the precursor peptides HalA1
      and HalA2 by their cognate lanthipeptide synthetases, HalM1 and HalM2,
      respectively. Coexpression studies of HalM1 and HalM2 with chimeric peptides
      consisting of the leader peptide of HalA1 and the core peptide of HalA2 (or vice
      versa) showed that the synthetases require both the cognate leader and core
      peptides for efficient processing. Investigation of the affinity in vitro showed
      that binding of the N-terminal leader peptide by HalM2 increases its affinity for
      the C-terminal core peptide. Thus, the two segments of the precursor peptide
      HalA2 synergistically bind to HalM2. 

PMID- 25619529
TI  - Multidisciplinary residential treatment can improve perceptual-motor function in
      obese children.
AB  - AIM: This study evaluated the effects of a 10-month multidisciplinary residential
      treatment programme on the perceptual-motor function of obese children and
      compared them to children with a healthy weight. METHODS: We studied 26 obese
      Belgian children (10 girls and 16 boys) with a mean age of 10.1 years (+/-1.4
      years), who followed a residential treatment programme consisting of moderate
      dietary restriction, psychological support and physical activity. The results
      were compared with 26 healthy weight children matched for age and gender. The
      anthropometrics and performance of both groups were assessed on two occasions, 10
      months apart, based on simple and choice reaction time tasks and a tracking task
      using a stylus and tablet. Time by body mass index group interactions were
      investigated using repeated measure ANCOVAs, with age included as a covariate.
      RESULTS: No significant interaction effect occurred in either task. In contrast,
      the obese participants showed a significant improvement in tracking performance
      over time during the stylus and tablet tests, demonstrating mean deviation from
      the ideal curve. No difference in performance between baseline and follow-up was
      observed in the healthy weight controls. CONCLUSION: Taking part in a
      multidisciplinary residential treatment programme improved the perceptual-motor
      function of obese children.

PMID- 25619531
TI  - Prevalence of Simkania negevensis in chlorinated water from spa swimming pools
      and domestic supplies.
AB  - AIMS: This study aimed to investigate the prevalence of Simkania negevensis in
      the chlorinated water of spa swimming pools and domestic network systems. METHODS
      AND RESULTS: A total of 10 and 36 samples were collected from two domestic water
      supplies and four spa facilities, respectively. Simkania negevensis was isolated
      in Acanthamoeba castellanii monolayers and detected by Gimenez staining and
      immunofluorescence test. Simkania negevensis DNA, extracted from the positive
      samples, was confirmed by a nested PCR assay followed by sequencing. Simkania
      negevensis was detected in 41.3% of samples (domestic water: 50%; untreated spa
      supply water: 25%; chlorinated spa pool water: 42.9%) from all the examined water
      systems in successive samplings performed in 1 year. The presence of S.
      negevensis was not correlated with the counts of Heterotrophic Bacteria and
      Pseudomonas aeruginosa. Unlike Legionella spp., which were never isolated from
      the swimming-pool water samples, S. negevensis was also detected in chlorinated
      spa water. CONCLUSIONS: This investigation shows that Simkania is widespread in
      natural and man-made aquatic environments, which may represent possible sources
      of infection: in the swimming pools, in particular, the aerosol generated by the
      water movement could increase the risk of inhalation of infected particles.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents the first evidence of
      the presence of S. negevensis in spa pool water. Sero-epidemiological surveys on
      spa users could help to clarify its transmission in this environment.

PMID- 25619530
TI  - An overview on adverse drug reactions to traditional Chinese medicines.
AB  - The safe use of Chinese materia medica (CMM) and products in traditional Chinese
      medicine (TCM) practice conventionally relies on correct pharmacognostic
      identification, good agricultural and manufacturing practices based on
      pharmacopoeia standards and rational/correct CMM combinations with TCM-guided
      clinical prescribing. These experience-based principles may not absolutely ensure
      safety without careful toxicological investigations when compared with
      development of new pharmaceutical drugs. Clinically observed toxicity reports
      remain as guidance for gathering toxicological evidence, though essential as
      pharmacovigilance, but are considered as late events for ensuring safety. The
      overview focuses on the following factors: global development of TCM that has
      affected conventional healthcare; examples of key toxic substances in CMM;
      reported adverse drug reactions (ADRs) consequential to taking CMM and TCM
      products; and proposals on rational approaches to integrate the knowledge of
      biomedical science and the principles of TCM practice for detecting early ADRs if
      both TCM products and orthodox drugs are involved. It is envisaged that good
      control of the quality and standards of CMM and proprietary Chinese medicines can
      certainly reduce the incidence of ADRs in TCM practice when these medications are
      used. 

PMID- 25619532
TI  - Indium-catalyzed, novel route to beta,beta-disubstituted indanones via tandem
      Nakamura addition-hydroarylation-decarboxylation sequence.
AB  - A novel method for the construction of beta,beta-disubstituted indanones has been
      developed via tandem Nakamura addition-hydroarylation-decarboxylation process.
      Indium(III) triflate was demonstrated as a versatile multitasking catalyst, which
      catalyzes three different chemical transformations under one-pot conditions.

PMID- 25619533
TI  - The effectiveness and cost-effectiveness of diversion and aftercare programmes
      for offenders using class A drugs: a systematic review and economic evaluation.
AB  - BACKGROUND: The societal costs of problematic class A drug use in England and
      Wales exceed L15B; drug-related crime accounts for almost 90% of costs. Diversion
      plus treatment and/or aftercare programmes may reduce drug-related crime and
      costs. OBJECTIVES: To assess the effectiveness and cost-effectiveness of
      diversion and aftercare for class A drug-using offenders, compared with no
      diversion. POPULATION: Adult class A drug-using offenders diverted to treatment
      or an aftercare programme for their drug use. INTERVENTIONS: Programmes to
      identify and divert problematic drug users to treatment (voluntary, court
      mandated or monitored services) at any point within the criminal justice system
      (CJS). Aftercare follows diversion and treatment, excluding care following prison
      or non-diversionary drug treatment. DATA SOURCES: Thirty-three electronic
      databases and government online resources were searched for studies published
      between January 1985 and January 2012, including MEDLINE, PsycINFO and ISI Web of
      Science. Bibliographies of identified studies were screened. The UK Drug Data
      Warehouse, the UK Drug Treatment Outcomes Research Study and published statistics
      and reports provided data for the economic evaluation. METHODS: Included studies
      evaluated diversion in adult class A drug-using offenders, in contact with the
      CJS. The main outcomes were drug use and offending behaviour, and these were
      pooled using meta-analysis. The economic review included full economic
      evaluations for adult opiate and/or crack, or powder, cocaine users. An economic
      decision analytic model, estimated incremental costs per unit of outcome gained
      by diversion and aftercare, over a 12-month time horizon. The perspectives
      included the CJS, NHS, social care providers and offenders. Probabilistic
      sensitivity analysis and one-way sensitivity analysis explored variance in
      parameter estimates, longer time horizons and structural uncertainty. RESULTS:
      Sixteen studies met the effectiveness review inclusion criteria, characterised by
      poor methodological quality, with modest sample sizes, high attrition rates,
      retrospective data collection, limited follow-up, no random allocation and
      publication bias. Most study samples comprised US methamphetamine users. Limited
      meta-analysis was possible, indicating a potential small impact of diversion
      interventions on reducing drug use [odds ratio (OR) 1.68, 95% confidence interval
      (CI) 1.12 to 2.53 for reduced primary drug use, and OR 2.60, 95% CI 1.70 to 3.98
      for reduced use of other drugs]. The cost-effectiveness review did not identify
      any relevant studies. The economic evaluation indicated high uncertainty because
      of variance in data estimates and limitations in the model design. The primary
      analysis was unclear whether or not diversion was cost-effective. The sensitivity
      analyses indicated some scenarios where diversion may be cost-effective.
      LIMITATIONS: Nearly all participants (99.6%) in the effectiveness review were
      American (Californian) methamphetamine users, limiting transfer of conclusions to
      the UK. Data and methodological limitations mean it is unclear whether or not
      diversion is effective or cost-effective. CONCLUSIONS: High-quality evidence for
      the effectiveness and cost-effectiveness of diversion schemes is sparse and does
      not relate to the UK. Importantly this research identified a range of
      methodological limitations in existing evidence. These highlight the need for
      research to conceptualise, define and develop models of diversion programmes and
      identify a core outcome set. A programme of feasibility, pilot and definitive
      trials, combined with process evaluation and qualitative research is recommended
      to assess the effectiveness and cost-effectiveness of diversionary interventions
      in class A drug-using offenders. FUNDING DETAILS: The National Institute for
      Health Research Health Technology Assessment programme.

PMID- 25619534
TI  - Vision concerns after mild traumatic brain injury.
AB  - OPINION STATEMENT: Mild traumatic brain injury (mTBI) can manifest with visual
      dysfunction including deficits in accommodation, vergence movements, versions,
      and field of vision as well increased photosensitivity and a decline in ocular
      and overall health. Patients with incomitant strabismus should be referred to an
      ophthalmologist for intervention. Patients with mTBI who experience
      photosensitivity, or deficits in accommodation, versions, vergences, or field of
      vision may benefit from vision rehabilitation. These therapies may include
      spectacles with tinting and a variety of prism combinations. Patients with
      chronic visual dysfunction following mTBI may benefit from occupational,
      vestibular, cognitive, and other forms of physical therapy.

PMID- 25619535
TI  - Decompressive craniectomy in neurocritical care.
AB  - OPINION STATEMENT: Decompressive craniectomy (DC) involves the removal of a
      portion of the skull in the setting of life threatening brain edema or
      potentially uncontrollable intracranial pressures. Often performed on an emergent
      basis, evaluation and arrangement for DC should be swift and decisive. However,
      the evidence base for DC in the wide range of conditions for which it is
      currently performed is still developing. The procedure is associated with a
      number of complications and ethical considerations; thus, its place in
      contemporary practice remains controversial. While randomized trials conducted in
      the last decade have provided valuable data on the indications, eligibility
      criteria, and outcomes for DC in the treatment of traumatic brain injury and
      malignant middle cerebral artery infarction, important outstanding issues
      continue to complicate the decision to pursue DC on an individual case basis and
      in the number of other clinical settings presenting with brain edema and
      intracranial hypertension. In this review, we present the existing evidence and
      remaining questions regarding DC in various neurologic conditions including
      traumatic brain injury, ischemic stroke, subarachnoid hemorrhage, spontaneous
      intracerebral hemorrhage, encephalitis, and others. We also discuss perioperative
      considerations and ethical issues likely to be encountered by clinicians caring
      for patients and families who are considering or have undergone DC.

PMID- 25619536
TI  - Imaging selection for reperfusion therapy in acute ischemic stroke.
AB  - OPINION STATEMENT: Neuroimaging is essential in the evaluation of the acute
      stroke patient. Computed tomography (CT) or magnetic resonance imaging (MRI)
      should be used to confirm the diagnosis of acute stroke, exclude stroke mimics,
      and triage patients for intravenous tissue plasminogen activator and endovascular
      revascularization therapies. Advanced neuroimaging techniques, including CT
      angiography, MR-angiography, CT-perfusion, and MR-perfusion should be used to
      further inform acute stroke treatment decisions. Patients considered for
      endovascular stroke therapy should have (1) a vascular occlusion that can be
      reached by an endovascular approach; (2) a small area of core cerebral
      infarction; and (3) viable tissue at risk of infarction if prompt
      revascularization is not achieved (penumbra).

PMID- 25619537
TI  - Treatment options for optic pathway gliomas.
AB  - OPINION STATEMENT: Gliomas that affect the optic pathways are for the most part
      low-grade neoplasms that often, but not always, have good prognoses. Optimal
      treatment and management of optic pathway gliomas remains unclear and the
      decision hinges upon several factors including patient age, tumor location, and
      visual symptoms. We favor a treatment approach that is dependent on the location
      of tumor within anterior, chiasmal or posterior/hypothalamic visual pathways. In
      children who are minimally or not symptomatic, we recommend observation rather
      than early treatment intervention. Most of these patients will have
      neurofibromatosis type 1 (NF1) based on the natural history and their pilocytic
      astrocytoma histology. Serial magnetic resonance imaging studies and formal neuro
      ophthalmology testing should enable close observation of these patients, with
      intervention being reserved for when tumor progression results in significant
      visual loss or proptosis. Chemotherapy is an accepted first line treatment, and a
      number of effective medications are available, although no agent has proven
      clearly superior. If progression is accompanied by the complete loss of vision,
      surgery can be utilized to help alleviate structural issues (ie, proptosis).
      Minimally symptomatic chiasmal or hypothalamic tumors that arise in the setting
      of NF1 can also be observed initially because of their favorable prognosis.
      Children with NF1 and chiasmal or posterior visual tumors who progress either on
      imaging or clinical grounds (ie, development of significant visual deficits)
      should be treated first with chemotherapy rather than radiation therapy to
      minimize the effects on the developing central nervous system. Individuals
      without NF1 presenting with a chiasmal or hypothalamic mass are candidates for
      biopsy to determine the underlying pathology of the lesion. Symptomatic patients
      with pilocytic astrocytoma should first receive chemotherapy. In contrast, other
      histologies including malignant optic pathway gliomas should be treated similar
      to other gliomas that occur in other locations with appropriate doses of
      radiation and chemotherapy.

PMID- 25619538
TI  - Opposite selection on behavioural types by active and passive fishing gears in a
      simulated guppy Poecilia reticulata fishery.
AB  - This study assessed whether fishing gear was selective on behavioural traits,
      such as boldness and activity, and how this was related with a productivity
      trait, growth. Female guppies Poecilia reticulata were screened for their
      behaviour on the shy-bold axis and activity, and then tested whether they were
      captured differently by passive and active fishing gear, here represented by a
      trap and a trawl. Both gears were selective on boldness; bold individuals were
      caught faster by the trap, but escaped the trawl more often. Boldness and gear
      vulnerability showed weak correlations with activity and growth. The results draw
      attention to the importance of the behavioural dimension of fishing: selective
      fishing on behavioural traits will change the trait composition of the
      population, and might eventually affect resilience and fishery productivity.

PMID- 25619539
TI  - Cystoscopic findings: a video tutorial.
AB  - INTRODUCTION AND HYPOTHESIS: Cystoscopy is frequently performed by gynecologists
      to ensure ureteral patency and to prevent bladder injury when performing
      concomitant gynecological procedures. Generally, there are no additional findings
      on cystoscopy; however, when abnormalities arise, they may require either
      observation or intervention. Our aim was to create a visual library of benign,
      malignant, and foreign-body pathological conditions incidentally encountered on
      cystoscopy. METHOD: Cystoscopic findings were videotaped at the time of routine
      surgical care. Regarding Institutional Review Board approval, individual consent
      was waived as the videos were de-identified and collected for educational
      purposes. RESULTS: Benign pathological conditions: squamous metaplasia,
      duplicated ureteral orifice, ureterocele, Hutch diverticulum, bladder
      trabeculation, urachal cyst, interstitial cystitis with and without Hunner's
      lesion, endometriosis in the bladder, port-wine stain due to Klippel-Trenaunay
      Weber syndrome, nephrogenic (mesonephric) metaplasia, and cystitis glandularis
      (intestinal metaplasia). Malignant pathological conditions: papillary urothelial
      neoplasm of low malignant potential (PUNLMP), carcinoma in situ (CIS), high-grade
      urothelial carcinoma, and urachal cancer. Foreign-body pathological conditions:
      edema from ureteral stents and stone-encrusted mesh. CONCLUSION: This video is
      intended to educate the audience on some incidental bladder findings seen on
      female cystoscopy. Many pathological conditions can be biopsied or treated
      immediately during the procedure; hence, early urology consultation is encouraged
      for most abnormalities.

PMID- 25619540
TI  - Is type 2 diabetes mellitus a predisposal cause for developing hepatocellular
      carcinoma?
AB  - Hepatic cancer stands as one of the frontier causes of cancer related mortality
      worldwide. Among the several risk factors already established, type 2 diabetes is
      now considered as one of the important risks in progression of liver cancer.
      Studies have shown that likelihood of occurrence of liver cancer is many folds
      higher in patients diagnosed with type II diabetes compared to patients without
      diabetes. Liver plays an important role in metabolism of glucose in our body, so
      may be type II diabetes as it is an important epiphenomenon of hepatic diseases
      such as liver cirrhosis, liver failure, fatty liver, chronic hepatitis and
      hepatocellular carcinoma. Some reports suggested that extensive change in enzyme
      structures in molecular level in diabetic patients may lead to liver function
      damage and hence accelerate hepatic cancer. Other strong links between these two
      diseases are "non alcoholic fatty liver diseases" and "nonalcoholic
      steatohepatitis" which are metabolic disorders caused by type II diabetes and
      eventually develops hepatocellular carcinoma. However, it still remains
      unanswered whether prevention of diabetes would effectively lower the chances of
      developing liver cancer or eliminating diabetes from the population would
      effectively reduce the liver cancer incidence. In this review, we will primarily
      focus on the molecular link between type2 diabetes and hepatic cancer and
      investigate underlying mechanism to establish type II diabetes as predisposed
      cause of hepatic cancer. 

PMID- 25619541
TI  - Predictive factors of follow-up non-attendance and mortality among adults with
      type 2 diabetes mellitus- an analysis of the Malaysian diabetes registry 2009.
AB  - This study examined the factors associated with follow-up non-attendance (FUNA)
      and mortality among the adult patients with type 2 diabetes mellitus (T2DM). Data
      on 57780 T2DM patients from the 2009 diabetes registry were analyzed using
      multinomial logistic mixed model. Out of 57780 patients, 3140 (5.4%) were lost to
      follow-up and 203 (0.4%) patients had died. Compared with patients who were under
      active follow-up, men (OR 1.37), neither on insulin (OR 1.72), nor on
      antiplatelet agents (OR 1.47), having higher HbA1c (OR 1.15), higher LDL-C (OR
      1.18) and complications (OR 1.33) were associated with FUNA. Older age (OR 1.09)
      and higher LDL-C (OR 2.27) have higher mortality. Across the four different
      health facilities, medication use (insulin and anti-platelet agents) to achieve
      better disease control in the younger age when diabetes complication is absent
      would not cause FUNA and might reduce mortality. 

PMID- 25619542
TI  - Complement activation and expression during chronic relapsing experimental
      autoimmune encephalomyelitis in the Biozzi ABH mouse.
AB  - Chronic relapsing experimental autoimmune encephalomyelitis (crEAE) in mice
      recapitulates many of the clinical and histopathological features of human
      multiple sclerosis (MS), making it a preferred model for the disease. In both,
      adaptive immunity and anti-myelin T cells responses are thought to be important,
      while in MS a role for innate immunity and complement has emerged. Here we sought
      to test whether complement is activated in crEAE and important for disease.
      Disease was induced in Biozzi ABH mice that were terminated at different stages
      of the disease to assess complement activation and local complement expression in
      the central nervous system. Complement activation products were abundant in all
      spinal cord areas examined in acute disease during relapse and in the progressive
      phase, but were absent in early disease remission, despite significant residual
      clinical disease. Local expression of C1q and C3 was increased at all stages of
      disease, while C9 expression was increased only in acute disease; expression of
      the complement regulators CD55, complement receptor 1-related gene/protein y
      (Crry) and CD59a was reduced at all stages of the disease compared to naive
      controls. These data show that complement is activated in the central nervous
      system in the model and suggest that it is a suitable candidate for exploring
      whether anti-complement agents might be of benefit in MS. 

PMID- 25619543
TI  - Differential contributions of plant Dicer-like proteins to antiviral defences
      against potato virus X in leaves and roots.
AB  - Members of the plant Dicer-like (DCL) protein family are the critical components
      of the RNA-silencing pathway that mediates innate antiviral defence. The distinct
      antiviral role of each individual DCL protein has been established with mostly
      based on observations of aerial parts of plants. Thus, although the roots are
      closely associated with the life cycle of many plant viruses, little is known
      about the antiviral activities of DCL proteins in roots. We observed that
      antiviral silencing strongly inhibits potato virus X (PVX) replication in roots
      of some susceptible Solanaceae species. Silencing of the DCL4 homolog in
      Nicotiana benthamiana partially elevated PVX replication levels in roots. In
      Arabidopsis thaliana, which was originally considered a non-host plant of PVX,
      high levels of PVX accumulation in inoculated leaves were achieved by
      inactivation of DCL4, while in the upper leaves and roots, it required the
      additional inactivation of DCL2. In transgenic A. thaliana carrying the PVX
      amplicon with a green fluorescent protein (GFP) gene insertion in the chromosome
      (AMP243 line), absence of DCL4 enabled high levels of PVX-GFP accumulation in
      various aerial organs but not in the roots, suggesting that DCL4 is critical for
      intracellular antiviral silencing in shoots but not in roots, where it can be
      functionally compensated by other DCL proteins. Together, the high level of
      functional redundancies among DCL proteins may contribute to the potent antiviral
      activities against PVX replication in roots. 

PMID- 25619544
TI  - From cage-in-cage MOF to N-doped and Co-nanoparticle-embedded carbon for oxygen
      reduction reaction.
AB  - By one-step pyrolysis of a unique "cage-in-cage" cobalt metal-organic framework,
      nitrogen-doped carbon cubes embedded with numerous metallic Co nanoparticles were
      obtained. A considerable amount of Co particles was encapsulated in thin carbon
      shells and formed the core-shell-like Co@C structure. With about 60 wt% Co
      particles in the prepared sample, the nanocomposites of Co nanoparticles and
      nitrogen-doped carbon show electrocatalytic activity for the oxygen reduction
      reaction (ORR) with an efficiency comparable to the commercial Pt/C catalyst, but
      with better durability and methanol-tolerance performance. The metallic Co
      nanoparticles were found to play an important role in enhancing the ORR activity
      of the nanocomposites. This simple one-step pyrolysis method provides a novel
      synthetic route for the synthesis of core-shell-like Co@C nano-composites. The
      synthesized material represents a highly active non-precious metal catalyst for
      ORR. 

PMID- 25619545
TI  - Prevalence, awareness, treatment, and control of hypertension in Lebanon.
AB  - The prevalence and factors related to hypertension (HTN) treatment and control
      are well investigated in the Western world but remain poorly understood in the
      Middle East and in middle-income countries such as Lebanon. In order to measure
      the prevalence, awareness, treatment, and control rates of HTN in Lebanon, the
      authors measured blood pressure (BP) in 1697 adults. The prevalence of optimal BP
      (<120/80 mm Hg) was 33% and that of pre-HTN (BP >=120/80 mm Hg but <140/90 mm Hg)
      was 30%. The prevalence, awareness, treatment, and control (among treated
      hypertensive) rates of HTN were 36.9%, 53%, 48.9%, and 54.2%, respectively.
      Overall, only 27% of patients with HTN had their BP under control. Awareness was
      the most important predictor of treatment. No predictor of control could be
      identified. The authors concluded that HTN is prevalent in Lebanon and its
      overall control is low. Improving awareness is the most important target for
      intervention. 

PMID- 25619546
TI  - Hiporfin-mediated photodynamic therapy in preclinical treatment of osteosarcoma.
AB  - This study was carried out to investigate the anti-tumor effect and mechanism of
      hiporfin-mediated photodynamic therapy (hiporfin-PDT) in osteosarcoma. We found
      that hiporfin accumulated mainly in the cytoplasm of osteosarcoma cells in a time
      and concentration-dependent manner. Hiporfin-PDT inhibited the proliferation,
      induced apoptosis and produced cell cycle arrest at G2M in osteosarcoma cell
      lines. Hiporfin-PDT increased the expression of cleaved-caspase-3, cleaved PARP
      1, Bax and RIP1 while it decreased the expression of Bcl-2; in addition, low
      concentration of hiporfin increased LC3 conversion. Furthermore, cell death
      caused by hiporfin-PDT could be rescued by Nec-1 but not by Z-VAD-FMK. Production
      of reactive oxygen species was increased after hiporfin-PDT. In vivo studies
      showed a significant decrease in tumor volume and weight after hiporfin-PDT in
      all three tumor mouse models investigated (subcutaneous and orthotopic).
      Histological analysis showed widespread cell apoptosis and necrosis after
      treatment. Immunohistochemistry also showed upregulation of cleaved-caspase-3 and
      downregulation of Bcl-2 after hiporfin-PDT. These results indicate that hiporfin
      PDT exhibits a killing effect in osteosarcoma both in vitro and in vivo, which is
      associated with apoptosis and necroptosis, while autophagy plays a protective
      role. All these findings shed light on a potential future clinical use for
      hiporfin in the treatment of osteosarcoma. 

PMID- 25619547
TI  - Lyme disease: sudden hearing loss as the sole presentation.
AB  - BACKGROUND: Lyme disease is an uncommon tick-borne multisystemic infection caused
      by Borrelia burgdorferi. The most common clinical manifestation is erythema
      migrans. In this report, a very unusual presentation of this condition is
      described, in which sudden onset sensorineural hearing loss was the sole
      presenting symptom. METHODS: Case report and review of English-language
      literature. RESULTS: A patient presented with sensorineural hearing loss, with no
      other symptoms or signs. Acute Lyme infection was detected by laboratory tests.
      Magnetic resonance imaging showed signs of labyrinthitis of the same inner ear.
      After hyperbaric oxygen and systemic antibiotic treatment, the patient showed
      total hearing recovery, and magnetic resonance imaging showed complete resolution
      of the labyrinthitis. CONCLUSION: To our knowledge, this is the first reported
      case of Lyme disease presenting only with sensorineural hearing loss. Borreliosis
      should be considered as an aetiological factor in sensorineural hearing loss.
      Adequate treatment may provide total recovery and prevent more severe forms of
      Lyme disease.

PMID- 25619548
TI  - Dialing torque preferences of people with diabetes when using insulin pens: a
      pilot study.
AB  - INTRODUCTION: Ergonomic dialing torque may enhance safety and comfort when
      setting doses with insulin pens. Limited data are available on the correlation of
      dialing torque and dialing comfort. METHODS: Three studies were performed with
      SoloSTAR((r)) (SS; Sanofi), FlexPen((r)) (FP; Novo Nordisk), KwikPen((r)) (KP;
      Eli Lilly) and FlexTouch((r)) (FT; Novo Nordisk) pens. Dialing behavior was
      examined with 20 pen-experienced people with diabetes. Participants dialed up to
      the maximum dose and back down to "zero" with each pen. Hand and pen movements
      were recorded by video camera and rotational speeds and angles calculated for
      each pen. In a laboratory study, dialing torque was measured discontinuously at a
      speed of 120 degrees /s, reflecting typical patient behavior. Sixteen pen
      experienced people with diabetes participated in a pilot preference study. Using
      a Likert scale, subjective dialing comfort rankings and ratings were obtained for
      each pen type and matched to their dialing torque. SS, FP, KP, and FT1 were
      investigated at 0-20 U each and at 60-80 U for FT2. RESULTS: SS was ranked most
      comfortable for up-dialing by 8 and down-dialing by 6 of the 16 participants,
      respectively; FP, 5 and 8; FT1, 2 and 1; and KP, 1 and 1. FT2 was ranked least
      comfortable by 12 and 10 participants. Comfort for up- and down-dialing was rated
      "very comfortable" for SS by 15 participants each, followed by FP (12 and 14), KP
      (10 each), and FT1 (9 and 7); FT2 was rated "less" or "not" comfortable by 10 and
      11 people, respectively. CONCLUSION: In this pilot study, subjective ratings of
      dialing comfort for different insulin pens by participants appear to concur with
      previous laboratory dialing torque study results. There appears to be a "torque
      comfort zone." Torques above 50 N mm reduced subjective handling comfort.
      Further, larger scale studies are needed to establish that dialing torque affects
      pen users' comfort.

PMID- 25619549
TI  - Loop diuretic dose adjustments after a hospitalization for heart failure:
      insights from ASCEND-HF.
AB  - AIMS: Loop diuretics are a cornerstone of heart failure (HF) treatment, but data
      regarding diuretic dose adjustments after a HF hospitalization and the
      association with subsequent outcomes are limited. This study was therefore
      conducted to determine these factors. METHODS AND RESULTS: We analysed data from
      6119 patients enrolled in ASCEND-HF, examining the association between loop
      diuretic use at the time of discharge, compared with admission, and the composite
      outcome of 30-day HF re-hospitalization or all-cause mortality. The majority of
      patients, 3921 (64%), were taking a loop diuretic on admission. At discharge,
      3411 (56%) patients were prescribed higher doses compared with admission,
      including 1867 (31%) initiating daily outpatient diuretics; 1912 (31%) had no
      dose change and 795 (13%) were prescribed lower doses compared with admission.
      Initiation of an oral loop diuretic at discharge was independently associated
      with better 30-day outcomes compared with no dose change [adjusted odds ratio
      (OR) 0.51, 95% confidence interval (CI) 0.37-0.68]. However, for patients that
      were already established on a loop diuretic prior to admission, change in the
      dose at discharge was not associated with improved outcomes compared with no dose
      change (adjusted OR 0.92, 95% CI 0.79-1.07). CONCLUSIONS: In a large
      multinational clinical trial, 56% of patients hospitalized with HF were either
      initiated on a daily loop diuretic at discharge or discharged on higher doses
      compared with admission. In patients established on diuretics prior to
      hospitalization, we found no association between changes to chronic doses at
      discharge and improved outcomes, whereas initiation of loop diuretic therapy was
      associated with better outcomes compared with no dose change.

PMID- 25619550
TI  - Telencephalic neurocircuitry and synaptic plasticity in rodent spatial learning
      and memory.
AB  - Spatial learning and memory in rodents represent close equivalents of human
      episodic declarative memory, which is especially sensitive to cerebral aging,
      neurodegeneration, and various neuropsychiatric disorders. Many tests and
      protocols are available for use in laboratory rodents, but Morris water maze and
      radial-arm maze remain the most widely used as well as the most valid and
      reliable spatial tests. Telencephalic neurocircuitry that plays functional roles
      in spatial learning and memory includes hippocampus, dorsal striatum and medial
      prefrontal cortex. Prefrontal-hippocampal circuitry comprises the major
      associative system in the rodent brain, and is critical for navigation in
      physical space, whereas interconnections between prefrontal cortex and dorsal
      striatum are probably more important for motivational or goal-directed aspects of
      spatial learning. Two major forms of synaptic plasticity, namely long-term
      potentiation, a lasting increase in synaptic strength between simultaneously
      activated neurons, and long-term depression, a decrease in synaptic strength,
      have been found to occur in hippocampus, dorsal striatum and medial prefrontal
      cortex. These and other phenomena of synaptic plasticity are probably crucial for
      the involvement of telencephalic neurocircuitry in spatial learning and memory.
      They also seem to play a role in the pathophysiology of two brain pathologies
      with episodic declarative memory impairments as core symptoms, namely Alzheimer's
      disease and schizophrenia. Further research emphasis on rodent telencephalic
      neurocircuitry could be relevant to more valid and reliable preclinical research
      on these most devastating brain disorders. This article is part of a Special
      Issue entitled SI: Brain and Memory. 

PMID- 25619551
TI  - Animacy-based predictions in language comprehension are robust: contextual cues
      modulate but do not nullify them.
AB  - Couldn't a humble coconut hurt a gardener? At least in the first instance, the
      brain seems to assume that it should not: we perceive inanimate entities such as
      coconuts as poor event instigators ("Actors"). Ideally, entities causing a change
      in another entity should be animate and this assumption not only influences event
      perception but also carries over to language comprehension. We present three
      auditory event-related brain potential (ERP) studies on the processing of
      inanimate and animate subjects and objects in simple transitive sentences in
      Tamil. ERP responses were measured at the second argument (event participant) in
      all three studies. Experiment 1 employed all possible animacy combinations of
      Actors and Undergoers (affected participants) in Actor- and Undergoer-initial
      verb-final orders. Experiments 2 and 3 employed a fairly novel context design
      that enabled us to compare ERPs evoked by identical auditory material to
      differing contextual expectations: Experiment 2 focussed on constructions in
      which an inanimate Actor acts upon an inanimate Undergoer, whereas Experiment 3
      examined whether and how a preceding context modulates the prediction for an
      ideal Actor. Results showed an N400 effect when the prediction for an ideal
      (animate) Actor following an Undergoer was not met, thus further supporting the
      cross-linguistically robust nature of animacy preferences. In addition, though
      specific contextual cues that are indicative of a forthcoming non-ideal Actor may
      reduce this negativity in comparison to when such cues are not available, they
      nevertheless do not nullify it, suggesting that animacy-based predictions are
      stronger than contextual cues in online language comprehension. 

PMID- 25619553
TI  - Inhibition of adenosine monophosphate-activated protein kinase reduces glial cell
      mediated inflammation and induces the expression of Cx43 in astroglias after
      cerebral ischemia.
AB  - We investigated the protective effect of adenosine monophosphate-activated
      protein kinase (AMPK) inhibition on cerebral ischemic injury of mice, and
      characterized the role of AMPK inhibition on astrocytes, microglias, and
      neuroinflammation. Focal cerebral ischemia was induced by middle cerebral artery
      occlusion (MCAO) in male Kunming mice, and Compound C was used to inhibit AMPK
      activity. The neurobehavioral scores, infarct volumes, phosphorylation of AMPK,
      activation of the glial cells, levels of connexin 43 (Cx43), and related
      inflammatory mediators were affected by the presence or absence of AMPK inhibitor
      Compound C. AMPK was activated after cerebral ischemia. AMPK inhibition reduced
      infarct size and improved neurological outcomes after 24h reperfusion of mice.
      Furthermore, our study revealed that the mechanisms of neuroprotection of AMPK
      inhibition may be as follows: (1) inhibiting the excessive activation of
      astrocyte and microglia cells, (2) stabilizing the expression of protective
      proteins such as Cx43 in astroglias, and (3) inhibiting the release of microglial
      pro-inflammatory factors. These results demonstrated that AMPK inhibition
      attenuated cerebral ischemic injury, at least in part, by glial cell-mediated
      protective effects in mice. 

PMID- 25619552
TI  - Long-term potentiation and the role of N-methyl-D-aspartate receptors.
AB  - N-methyl-D-aspartate receptors (NMDARs) are known for their role in the induction
      of long-term potentiation (LTP). Here we start by reviewing the early evidence
      for their role in LTP at CA1 synapses in the hippocampus. We then discuss more
      recent evidence that NMDAR dependent synaptic plasticity at these synapses can be
      separated into mechanistically distinct components. An initial phase of the
      synaptic potentiation, which is generally termed short-term potentiation (STP),
      decays in an activity-dependent manner and comprises two components that differ
      in their kinetics and NMDAR subtype dependence. The faster component involves
      activation of GluN2A and GluN2B subunits whereas the slower component involves
      activation of GluN2B and GluN2D subunits. The stable phase of potentiation,
      commonly referred to as LTP, requires activation of primarily triheteromeric
      NMDARs containing both GluN2A and GluN2B subunits. In new work, we compare STP
      with a rebound potentiation (RP) that is induced by NMDA application and conclude
      that they are different phenomena. We also report that NMDAR dependent long-term
      depression (NMDAR-LTD) is sensitive to a glycine site NMDAR antagonist. We
      conclude that NMDARs are not synonymous for either LTP or memory. Whilst
      important for the induction of LTP at many synapses in the CNS, not all forms of
      LTP require the activation of NMDARs. Furthermore, NMDARs mediate the induction
      of other forms of synaptic plasticity and are important for synaptic
      transmission. It is, therefore, not possible to equate NMDARs with LTP though
      they are intimately linked. This article is part of a Special Issue entitled SI:
      Brain and Memory.

PMID- 25619554
TI  - Reducing patient posture variability using the predicted couch position.
AB  - A method is presented in which the couch position is predicted before the
      treatment instead of obtaining a reference position at the first treatment
      fraction. This prevents systematic differences in patient posture between
      preparation and treatment. In literature, only limited data are available on
      couch positioning. We position our patients at the planned couch position,
      allowing a small difference between skin marks and lasers, followed by online
      imaging. For a 3-month period, our standard deviations (mm) in couch position in
      the vertical, longitudinal, and lateral directions were head and neck-1.6, 2.8,
      and 2.5; thorax-2.9, 5.5, and 4.5; breast-3.0, 4.1, and 4.0; and pelvis-3.5, 4.0,
      and 4.7, respectively. We have improved the reproducibility of patient posture in
      our institute by using the predicted couch position. Our data may serve as a
      reference for other institutes because the couch position variation is less than
      that published in literature. 

PMID- 25619555
TI  - Radiation treatment for the right naris in a pediatric anesthesia patient using
      an adaptive oral airway technique.
AB  - Radiation therapy for pediatric patients often includes the use of intravenous
      anesthesia with supplemental oxygen delivered via the nasal cannula. Here, we
      describe the use of an adaptive anesthesia technique for electron irradiation of
      the right naris in a preschool-aged patient treated under anesthesia. The need
      for an intranasal bolus plug precluded the use of standard oxygen
      supplementation. This novel technique required the multidisciplinary expertise of
      anesthesiologists, radiation therapists, medical dosimetrists, medical
      physicists, and radiation oncologists to ensure a safe and reproducible treatment
      course. 

PMID- 25619556
TI  - Encapsulation of alpha-Fe2O3 nanoparticles in graphitic carbon microspheres as
      high-performance anode materials for lithium-ion batteries.
AB  - A novel "spray drying-carbonization-oxidation" strategy has been developed for
      the fabrication of alpha-Fe2O3-graphitic carbon (alpha-Fe2O3@GC) composite
      microspheres, in which alpha-Fe2O3 nanoparticles with sizes of 30-50 nm are well
      encapsulated by onion-like graphitic carbon shells with a thickness of 5-10 nm.
      In the constructed composite, the alpha-Fe2O3 nanoparticles act as the primary
      active material, providing a high capacity. Meanwhile, the graphitic carbon
      shells serve as the secondary active component, structural stabilizer,
      interfacial stabilizer, and electron-highway. As a result, the synthesized alpha
      Fe2O3@GC nanocomposite exhibits a superior lithium-ion battery performance with a
      high reversible capacity (898 mA h g(-1) at 400 mA g(-1)), outstanding rate
      capability, and excellent cycling stability. Our product, in terms of the facile
      and scalable preparation process and excellent electrochemical performance,
      demonstrates its great potential as a high-performance anode material for lithium
      ion batteries. 

PMID- 25619557
TI  - Patient awareness of need for hepatitis a vaccination (prophylaxis) before
      international travel.
AB  - INTRODUCTION: Although hepatitis A virus (HAV) infection is preventable through
      vaccination, cases associated with international travel continue to occur. The
      purpose of this study was to examine the frequency of international travel and
      countries visited among persons infected with HAV and assess reasons why
      travelers had not received hepatitis A vaccine before traveling. METHODS: Using
      data from sentinel surveillance for HAV infection in seven US counties during
      1996 to 2006, we examined the role of international travel in hepatitis A
      incidence and the reasons for patients not being vaccinated. RESULTS: Of 2,002
      hepatitis A patients for whom travel history was available, 300 (15%) reported
      traveling outside of the United States. Compared to non-travelers, travelers were
      more likely to be female [odds ratio (OR) = 1.74 (95% confidence interval [95%
      CI], 1.35, 2.24)], aged 0 to 17 years [OR = 3.30 (1.83, 5.94)], Hispanic [OR =
      3.69 (2.81, 4.86)], Asian [OR = 2.00 (1.06, 3.77)], and were less likely to be
      black non-Hispanic [OR = 0.30 (0.11, 0.82)]. The majority, 189 (61.6%), had
      traveled to Mexico. The most common reason for not getting pre-travel vaccination
      was "Didn't know I could [or should] get shots" [100/154 (65%)]. CONCLUSION: Low
      awareness of HAV vaccination was the predominant reason for not being protected
      before travel. Different modes of traveler education could improve prevention of
      hepatitis A. To highlight the risk of infection before traveling to endemic
      countries including Mexico, travel and consulate websites could list reminders of
      vaccine recommendations.

PMID- 25619558
TI  - OntoMate: a text-mining tool aiding curation at the Rat Genome Database.
AB  - The Rat Genome Database (RGD) is the premier repository of rat genomic, genetic
      and physiologic data. Converting data from free text in the scientific literature
      to a structured format is one of the main tasks of all model organism databases.
      RGD spends considerable effort manually curating gene, Quantitative Trait Locus
      (QTL) and strain information. The rapidly growing volume of biomedical literature
      and the active research in the biological natural language processing (bioNLP)
      community have given RGD the impetus to adopt text-mining tools to improve
      curation efficiency. Recently, RGD has initiated a project to use OntoMate, an
      ontology-driven, concept-based literature search engine developed at RGD, as a
      replacement for the PubMed (http://www.ncbi.nlm.nih.gov/pubmed) search engine in
      the gene curation workflow. OntoMate tags abstracts with gene names, gene
      mutations, organism name and most of the 16 ontologies/vocabularies used at RGD.
      All terms/ entities tagged to an abstract are listed with the abstract in the
      search results. All listed terms are linked both to data entry boxes and a term
      browser in the curation tool. OntoMate also provides user-activated filters for
      species, date and other parameters relevant to the literature search. Using the
      system for literature search and import has streamlined the process compared to
      using PubMed. The system was built with a scalable and open architecture,
      including features specifically designed to accelerate the RGD gene curation
      process. With the use of bioNLP tools, RGD has added more automation to its
      curation workflow. Database URL: http://rgd.mcw.edu. 

PMID- 25619560
TI  - A solid-state effect responsible for an organic quintet state at room temperature
      and ambient pressure.
AB  - A stable organic diradicaloid with an intermolecular quintet at room temperature
      as a polycrystalline solid is studied. The conclusion is supported by the
      observation of the DeltaMs = +/-2 forbidden transition, electron spin resonance
      (ESR) simulations, and density functional theory (DFT) calculations. In addition,
      the molecule, as the active component of a device, is an outstanding near
      infrared photodetector with detectivity over 10(11) cm Hz(1/2) W(-1) at 1200 nm. 

PMID- 25619559
TI  - Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens
      for locally advanced squamous cell carcinoma of the head and neck.
AB  - We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and
      concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent
      survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease
      specific survival (DSS) and overall survival (OS) between patients given nab
      paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical
      controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C).
      Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n
      = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin
      concurrent with definitive radiotherapy. T and N classification and smoking
      history were similar between the two groups and within p16-positive and p16
      negative subsets. The median duration of follow-up for living patients in the APF
      C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C.
      The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval
      (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004).
      Disease progression that resulted in death was more frequent in the TPF-C group
      (39%) compared with the APF-C group (3%) when adjusted for competing risks of
      death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2
      year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P =
      0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C
      was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS
      for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%)
      (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel
      based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16
      positive OPSCC.

PMID- 25619561
TI  - Enhancing the cross-cultural adaptation and validation process: linguistic and
      psychometric testing of the Brazilian-Portuguese version of a self-report measure
      for dry eye.
AB  - OBJECTIVES: To provide a reliable, validated, and culturally adapted instrument
      that may be used in monitoring dry eye in Brazilian patients and to discuss the
      strategies for the enhancement of the cross-cultural adaptation and validation
      process of a self-report measure for dry eye. METHODS: The cross-cultural
      adaptation process (CCAP) of the original Ocular Surface Disease Index (OSDI)
      into Brazilian-Portuguese was conducted using a 9-step guideline. The synthesis
      of translations was tested twice, for face and content validity, by different
      subjects (focus groups and cognitive interviews). The expert committee
      contributed on several steps, and back translations were based on the final
      rather than the prefinal version. For validation, the adapted version was applied
      in a prospective longitudinal study to 101 patients from the Dry Eye Clinic at
      the General Hospital of the University of Sao Paulo, Brazil. Simultaneously to
      the OSDI, patients answered the short form-36 health survey (SF-36) and the 25
      item visual function questionnaire (VFQ-25) and underwent clinical evaluation.
      Internal consistency, test-retest reliability, and measure validity were
      assessed. RESULTS: Cronbach's alpha value of the cross-culturally adapted
      Brazilian-Portuguese version of the OSDI was 0.905, and the intraclass
      correlation coefficient was 0.801. There was a statistically significant
      difference between OSDI scores in patients with dry eye (41.15 +/- 27.40) and
      without dry eye (17.88 +/- 17.09). There was a negative association between OSDI
      and VFQ-25 total score (P < 0.01) and between the OSDI and five SF-36 domains.
      OSDI scores correlated positively with lissamine green and fluorescein staining
      scores (P < 0.001) and negatively with Schirmer test I and tear break-up time
      values (P < 0.001). CONCLUSION: Although most of the reviewed guidelines on CCAP
      involve well-defined steps (translation, synthesis/reconciliation, back
      translation, expert committee review, pretesting), the proposed methodological
      steps have not been applied in a uniform way. The translation and adaptation
      process requires skill, knowledge, experience, and a considerable investment of
      time to maximize the attainment of semantic, idiomatic, experiential, and
      conceptual equivalence between the source and target questionnaires. A well
      established guideline resulted in a culturally adapted Brazilian-Portuguese
      version of the OSDI, tested and validated on a sample of Brazilian population,
      and proved to be a valid and reliable instrument for assessing patients with dry
      eye syndrome in Brazil.

PMID- 25619562
TI  - Systematic reviews examining implementation of research into practice and impact
      on population health are needed.
AB  - OBJECTIVES: To examine the research translation phase focus (T1-T4) of systematic
      reviews published in the Cochrane Database of Systematic Reviews (CDSR) and
      Database of Abstracts of Reviews of Effects (DARE). Briefly, T1 includes reviews
      of basic science experiments; T2 includes reviews of human trials leading to
      guideline development; T3 includes reviews examining how to move guidelines into
      policy and practice; and T4 includes reviews describing the impact of changing
      health practices on population outcomes. STUDY DESIGN AND SETTING: A cross
      sectional audit of randomly selected reviews from CDSR (n = 500) and DARE (n =
      500) was undertaken. The research translation phase of reviews, overall and by
      communicable disease, noncommunicable disease, and injury subgroups, were coded
      by two researchers. RESULTS: A total of 898 reviews examined a communicable,
      noncommunicable, or injury-related condition. Of those, 98% of reviews within
      CDSR focused on T2, and the remaining 2% focused on T3. In DARE, 88% focused on
      T2, 8.7% focused on T1, 2.5% focused on T3, and 1.3% focused on T4. Almost all
      reviews examining communicable (CDSR 100%, DARE 93%), noncommunicable (CDSR 98%,
      DARE 87%), and injury (CDSR 95%, DARE 88%) were also T2 focused. CONCLUSION: Few
      reviews exist to guide practitioners and policy makers with implementing evidence
      based treatments or programs.

PMID- 25619563
TI  - The comparative performance of PMI estimation in skeletal remains by three
      methods (C-14, luminol test and OHI): analysis of 20 cases.
AB  - When estimating post-mortem interval (PMI) in forensic anthropology, the only
      method able to give an unambiguous result is the analysis of C-14, although the
      procedure is expensive. Other methods, such as luminol tests and histological
      analysis, can be performed as preliminary investigations and may allow the
      operators to gain a preliminary indication concerning PMI, but they lack
      scientific verification, although luminol testing has been somewhat more
      accredited in the past few years. Such methods in fact may provide some help as
      they are inexpensive and can give a fast response, especially in the phase of
      preliminary investigations. In this study, 20 court cases of human skeletonized
      remains were dated by the C-14 method. For two cases, results were
      chronologically set after the 1950s; for one case, the analysis was not possible
      technically. The remaining 17 cases showed an archaeological or historical
      collocation. The same bone samples were also screened with histological
      examination and with the luminol test. Results showed that only four cases gave a
      positivity to luminol and a high Oxford Histology Index (OHI) score at the same
      time: among these, two cases were dated as recent by the radiocarbon analysis.
      Thus, only two false-positive results were given by the combination of these
      methods and no false negatives. Thus, the combination of two qualitative methods
      (luminol test and microscopic analysis) may represent a promising solution to
      cases where many fragments need to be quickly tested.

PMID- 25619564
TI  - Fracture mode control: a bio-inspired strategy to combat catastrophic damage.
AB  - The excellent mechanical properties of natural biomaterials have attracted
      intense attention from researchers with focus on the strengthening and toughening
      mechanisms. Nevertheless, no material is unconquerable under sufficiently high
      load. If fracture is unavoidable, constraining the damage scope turns to be a
      practical way to preserve the integrity of the whole structure. Recent studies on
      biomaterials have revealed that many structural biomaterials tend to be
      fractured, under sufficiently high indentation load, through ring cracking which
      is more localized and hence less destructive compared to the radial one. Inspired
      by this observation, here we explore the factors affecting the fracture mode of
      structural biomaterials idealized as laminated materials. Our results suggest
      that fracture mode of laminated materials depends on the coating/substrate
      modulus mismatch and the indenter size. A map of fracture mode is developed,
      showing a critical modulus mismatch (CMM), below which ring cracking dominates
      irrespective of the indenter size. Many structural biomaterials in nature are
      found to have modulus mismatch close to the CMM. Our results not only shed light
      on the mechanics of inclination to ring cracking exhibited by structural
      biomaterials but are of great value to the design of laminated structures with
      better persistence of structural integrity. 

PMID- 25619565
TI  - miR-375 regulates the canonical Wnt pathway through FZD8 silencing in arthritis
      synovial fibroblasts.
AB  - Whether the rheumatoid arthritis (RA) pathogenesis is regulated by microRNA
      (miRNA) is not entirely clear. In this study, we found that miR-375 was down
      regulated significantly in fibroblast-like synoviocytes (FLS) in adjuvant-induced
      arthritis (AIA) rat model compared with control. Because the web-based software
      TargetScan and PicTar predict Frizzled 8 (FZD8) as the target of miR-375, we
      investigated whether up-regulated miR-375 plays a role in the activation of the
      canonical Wnt signaling by targeting the FZD8. Furthermore, the purpose of the
      present experiments was also to determine the role of miR-375 in the pathogenesis
      of AIA rat model and to ascertain the effects of FZD8 in this process. Real time
      qPCR, Western blotting, ELISA and ChIP assay were used to assess the inhibited
      role of miR-375 in the pathogenesis of AIA rat model and the canonical Wnt
      signaling. RNA interference was also used to detect the role of knockdown of
      dephosphorylated beta-catenin. Luciferase reporter gene and related methods were
      performed to determine the FZD8 as the target of miR-375. The increased miR-375
      inhibited the pathogenesis of AIA rat model as indicated by decreases in the
      several disease markers, such as MMP3 and fibronectin. Interestingly, miR-375
      also inhibited the canonical Wnt signaling, and the stabilized form of beta
      catenin blocked the miR-375 effects. FZD8 was identified as the target of miR-375
      in AIA rat model by the firefly luciferase reporter gene. In summary, our results
      demonstrate that miR-375 regulates the pathogenesis of AIA rat model through the
      canonical Wnt signaling pathway. This discovery may provide new targets for
      therapeutic intervention to benefit RA patients. 

PMID- 25619566
TI  - Older adults' favorite activities are resoundingly active: findings from the
      NHATS study.
AB  - Activity is associated with health among older adults yet older adults' favorite
      activities have rarely been investigated. We analyzed the community dwelling,
      cognitively-intact sample of NHATS, a nationally representative sample of adults
      >= 65, who had named their favorite activities (N = 5247). Logistic regression
      models estimated the odds of choosing a physical activity controlling for
      demographics, self-rated health, and disability. For all ages, four of the top
      five most common favorite activities were active: walking/jogging (14%), outdoor
      maintenance (13%), playing sports (8.9%), and other physical activity (8.7%).
      These findings sustain in 65-75 year olds. Even in 80-84 year olds, 3 of the top
      five activities are active. These findings vary by self-rated health (OR = 0.71,
      p < 0.001), disability (OR = 0.72, p < 0.001) and gender (OR = 0.52, p < 0.001).
      Policy makers, clinicians, and urban planners can use these results in their
      work.

PMID- 25619568
TI  - The role of Mott-Schottky heterojunctions in Ag-Ag8SnS6 as counter electrodes in
      dye-sensitized solar cells.
AB  - Well-defined uniform pyramidal Ag-Ag8SnS6 heterodimers are prepared via a one-pot
      method. A plausible formation mechanism for the unique structures based on a seed
      growth process and an etching effect due to oleylamine is proposed. The formed
      metal-semiconductor Mott-Schottky heterojunction promotes electron transfer from
      semiconducting Ag8 SnS6 to metallic Ag, which catalyzes the reduction of I3 (-)
      to I(-). When used as counter electrode in dye-sensitized solar cells, the
      heterodimers show comparable performance to platinum.

PMID- 25619567
TI  - Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen
      antibody-induced arthritis.
AB  - Dual-specificity phosphatase 2 (Dusp2; also called phosphatase of activated cells
      1, PAC1) is highly expressed in activated immune cells. We examined whether a
      potential inhibitor of Dusp2, salubrinal, prevents inflammatory cytokine
      expression in immune cells and arthritic responses in a mouse model of anti
      collagen antibody-induced arthritis (CAIA). Salubrinal is a synthetic chemical
      that inhibits de-phosphorylation of eukaryotic translation initiation factor 2
      alpha (eIF2alpha). In this study, we examined the effects of salubrinal on
      expression of inflammation linked genes as well as a family of DUSP genes using
      genome-wide microarrays, qPCR, and RNA interference. We also evaluated the
      effects of salubrinal on arthritic responses in CAIA mice using clinical and
      histological scores. The results revealed that salubrinal decreased inflammatory
      gene expression in macrophages, T lymphocytes, and mast cells. Dusp2 was
      suppressed by salubrinal in LPS-activated macrophages as well as PMA/ionomycin
      activated T lymphocytes and mast cells. Furthermore, a partial silencing of Dusp2
      downregulated IL1beta and Cox2, and the inflammatory signs of CAIA mice were
      significantly suppressed by salubrinal. Collectively, this study presents a novel
      therapeutic possibility of salubrinal for inflammatory arthritis such as RA
      through inhibition of Dusp2. 

PMID- 25619569
TI  - Post-thrombolysis haemostasis changes after rt-PA treatment in acute cerebral
      infarct. Correlations with cardioembolic aetiology and outcome.
AB  - BACKGROUND: Little is known, in man, in the post-thrombolytic molecular dynamics
      of haemostasis, particularly the effect of rt-PA on antifibrinolytic components
      such as alpha2 anti-plasmin and Factor XIII. AIMS AND HYPOTHESIS: The purpose of
      this study was to systematically determine changes in coagulation and
      fibrinolytic parameters after thrombolysis with rt-PA during 24h. We also aimed
      to correlate these parameters with different acute ischemic stroke subtypes and
      global outcome. METHODS: Eighty consecutive patients with cerebral infarcts
      treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2
      antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers
      measured at baseline (h0), 2 (h2) and 24h (h24) after initiation of thrombolysis.
      Correlations between the variations of these components were statistically
      studied, using the Spearman rank test or the Pearson test. These haemostatic
      parameters were also compared with cardioembolic and non cardioembolic patients,
      as well as between poor and favourable outcome patients. RESULTS: Between h0 and
      h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII
      was observed, while an increase in FDP and D-Dimers took place. These values
      returned to the initial levels at h24. At 2h, the decrease in fibrinogen was
      significantly correlated with that of plasminogen (0.48, p=0.01), alpha2
      antiplasmin (0.48, p=0.004), and factor XIII (0.44, p=0.01); the decrease in
      plasminogen was significantly correlated with those of antifibrinolytic
      components, factor XIII (0.47, p=0.02) and alpha2-antiplasmin (r=0.77, p<0.001).
      These variations were independent of NIHSS. Cardioembolic infarcts showed a
      statistically significant greater h0-h2 decrease in plasminogen (p=0.04) and an
      h0-h2 increase in FDP (p=0.02). Poor outcome was linked to low plasminogen values
      at 2 and 24h. CONCLUSIONS: Supposed to be fibrin-specific, rt-PA induces a
      decrease in circulating fibrinogen, significantly linked to a decrease in
      plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII
      and alpha2-antiplasmin is also observed. At 2h, a significant decrease in
      plasminogen and a significant increase in fibrin(ogen) degradation products (FDP)
      are observed in cardioembolic infarcts, and appear as early independent
      predictors of this aetiology. A low plasminogen value at 2h is potentially
      predictive of poor prognosis at 3months.

PMID- 25619570
TI  - Morphometric and high resolution scanning electron microscopy analysis of low
      level laser therapy and latex protein (Hevea brasiliensis) administration
      following a crush injury of the sciatic nerve in rats.
AB  - This study evaluated the effect of low-level laser therapy (LLLT; 15 J/cm(2)) and
      a latex protein (F1) on a crush injury of the sciatic (ischiadicus) nerve.
      Seventy-two rats (male, 250 g) were divided into 6 groups: CG, control; EG,
      exposed nerve; IG, injured nerve without treatment; LG, injured nerve with LLLT;
      HG, injured nerve with F1; and LHG, injured nerve with LLLT and F1. After 4 or 8
      weeks, the animals were euthanized and samples of the sciatic nerve were
      collected for morphometric and high-resolution scanning electron microscopy
      (HRSEM) analysis. After 4 weeks, the morphometry revealed improvements in the
      treated animals, and the HG appeared to be the most similar to the CG; after 8
      weeks, the injured groups showed improvements compared to the previous period,
      and the results of the treatment groups were more similar to one another. At
      HRSEM after 4 weeks, the treated groups were similar and showed improvement
      compared to the IG; after 8 weeks, the LHG and HG had the best results. In
      conclusion, the treatments resulted in improvement after the nerve injury, and
      this recovery was time-dependent. In addition, the use of the F1 resulted in the
      best morphometric and ultrastructural findings.

PMID- 25619571
TI  - Putaminal hypointensity on T2*-weighted MR imaging is the most practically useful
      sign in diagnosing multiple system atrophy: A preliminary study.
AB  - OBJECTIVE: To identify useful MRI abnormalities in the putamen for diagnosing
      multiple system atrophy. METHODS: Patients with multiple system atrophy (n=15),
      Parkinson's disease (n=16), or progressive supranuclear palsy (n=9) and healthy
      controls (n=10) were enrolled. Using a visual analog scale, 4 examiners
      independently rated high-intensity signals along the lateral putamen on T2
      weighted and T2*-weighted images, low-intensity signals within the putamen on T2
      weighted and T2*-weighted images, and putaminal atrophy. Receiver operating
      characteristic analyses were performed, and the area under the receiver operating
      characteristic curve was calculated. RESULTS: For differentiating multiple system
      atrophy from progressive supranuclear palsy, Parkinson's disease, and healthy
      controls, the mean area under the curve values was the highest for low-intensity
      signals within the putamen on T2*-weighted images (0.797, 0.867, 0.896,
      respectively). Variations in the area under the curve values among the 4
      examiners were the smallest in low-intensity signals within the putamen on T2*
      weighted images. Good inter-rater reliability was achieved for low-intensity
      signals within the putamen on T2*-weighted images and high-intensity signals
      along the lateral putamen on T2*-weighted images. CONCLUSION: Low-intensity
      signals within the putamen on T2*-weighted images is the most useful MRI
      abnormality for diagnosing multiple system atrophy.

PMID- 25619572
TI  - DNA-encapsulated chain and wire-like beta-MnO2 organosol for oxidative
      polymerization of pyrrole to polypyrrole.
AB  - A DNA-encapsulated chain and wire-like beta-MnO2 organosols have been synthesized
      utilizing a two-phase water-toluene extraction procedure at room temperature
      (RT). The beta-MnO2 organosol was prepared by transferring KMnO4 and DNA from
      aqueous solution separately to an organic solvent (toluene) using a phase
      transfer catalyst, mixing both organic solutions together, and subsequent
      reduction with NaBH4. The eventual diameters of the MnO2 particles in chain-like
      and wire-like morphologies were ~1-2 nm and ~1.8 +/- 0.2 nm, respectively,
      whereas the nominal length of the DNA-MnO2 chains was ~2-3 MUm. Different
      morphologies of the MnO2 organosol were synthesized by simply tuning the DNA to
      KMnO4 molar ratio. The synthesized particles were successfully re-dispersed in
      different organic solvents for application in various organic reactions. The
      potential of the DNA-MnO2 organosol as a catalyst has been tested in the organic
      catalytic reaction for the oxidative polymerization of pyrrole to polypyrrole,
      using the DNA-MnO2 organosol as a potential catalyst. The synthesis process was
      simple, reproducible and robust. In future, the present process might be utilized
      for the formation of other nanomaterials in organic solvents, with specific
      morphologies and uses in a variety of catalytic reactions and energy storage
      applications. 

PMID- 25619573
TI  - Discussion.

PMID- 25619574
TI  - Twelve-year results of fenestrated endografts for juxtarenal and group IV
      thoracoabdominal aneurysms.
AB  - OBJECTIVE: The practice of using fenestrated endografts to treat juxtarenal and
      group IV thoracoabdominal aortic aneurysms (TAAAs) has become more accepted, but
      long-term outcomes are still unknown. We report long-term survival,
      complications, and branch-related outcomes from a single-center experience.
      METHODS: The study included consecutive patients enrolled prospectively into a
      physician-sponsored investigational device exemption classified as undergoing
      group IV TAAA or juxtarenal aneurysm repair by the treating surgeon using
      fenestrated endografts. Device morphology was used to subclassify this group of
      patients. Long-term survival and a composite outcome of secondary intervention,
      branch occlusion, stent migration, endoleak, aneurysm growth, or spinal cord
      injury were calculated. Descriptive analysis of branch-related outcomes and need
      for any reintervention was performed. Univariate and multivariate analysis of
      mortality and the composite outcome was performed to determine associative risks.
      RESULTS: Long-term survival for patients with juxtarenal and group IV TAAA
      aneurysms treated with fenestrated stent grafts was 20% at 8 years. Multivariate
      analysis showed long-term survival for this patient population was negatively
      associated with increasing age, congestive heart failure, cancer, and previous
      aneurysm repair. The risk of spinal cord ischemia (SCI) in this group was 1.2%
      and of aortic-related mortality was 2%. The risk of a spinal event increased with
      coverage above the celiac artery (52 mm of coverage above the celiac artery in
      patients with SCI vs 33 mm without SCI; P = .099). More complex device
      configurations were more likely to require an increased rate of reinterventions,
      and patients with celiac fenestrations were more likely to experience celiac
      occlusion over time (3.5% vs 0.5%; P = .019). However, less complex designs were
      complicated by an increased risk of type I endoleak over time (10.4% for renal
      fenestrations only vs 1.9% for others; P < .01). As experience evolved, there was
      a trend to increase the number of fenestrations in devices treating the same
      anatomy. CONCLUSIONS: The use of fenestrated devices to treat juxtarenal and
      group IV TAAA is safe and effective in long-term follow-up. Mortality in this
      patient population is largely not aortic-related. Devices designed for
      fenestrated repair of juxtarenal and group IV thoracoabdominal aneurysms within a
      physician sponsored investigational device exemption have changed over time.
      Further research is needed to determine the best configuration to treat aneurysms
      requiring coverage proximal to the celiac artery.

PMID- 25619575
TI  - Discussion.

PMID- 25619576
TI  - A rare type of supra-aortic branches variation.

PMID- 25619577
TI  - Posterior nutcracker syndrome in a child.

PMID- 25619578
TI  - Obligations and frustrations with high-risk patients: ethics of physicians'
      evaluations.
AB  - A surgeon, Dr A. Droit, has been following a 97-year-old male with a type IV
      thoracoabdominal aneurysm, which became symptomatic this morning and is leaking.
      The patient is frail but active with no important comorbidities. The anatomy
      demands an open procedure. The patient is a former renowned physician who has
      been a longtime family friend of Dr Droit-like a grandfather. He presented
      incoherent with sagging blood pressure. A complicating factor is that Dr D. Rag,
      the chief anesthesiologist, decided that neither he nor any of his staff would
      provide anesthesia. Dr Droit knows an anesthesiologist who handles high-risk
      patients at another hospital in the medical center. The patient has worsened over
      the last hour, is becoming more unstable, and is unable to respond but his wife
      wishes to consent for surgery. What should Dr Droit do? 

PMID- 25619579
TI  - Kinematics effectively delineate accomplished users of endovascular robotics with
      a physical training model.
AB  - OBJECTIVE: Endovascular robotics systems, now approved for clinical use in the
      United States and Europe, are seeing rapid growth in interest. Determining who
      has sufficient expertise for safe and effective clinical use remains elusive. Our
      aim was to analyze performance on a robotic platform to determine what defines an
      expert user. METHODS: During three sessions, 21 subjects with a range of
      endovascular expertise and endovascular robotic experience (novices <2 hours to
      moderate-extensive experience with >20 hours) performed four tasks on a training
      model. All participants completed a 2-hour training session on the robot by a
      certified instructor. Completion times, global rating scores, and motion metrics
      were collected to assess performance. Electromagnetic tracking was used to
      capture and to analyze catheter tip motion. Motion analysis was based on
      derivations of speed and position including spectral arc length and total number
      of submovements (inversely proportional to proficiency of motion) and duration of
      submovements (directly proportional to proficiency). RESULTS: Ninety-eight
      percent of competent subjects successfully completed the tasks within the given
      time, whereas 91% of noncompetent subjects were successful. There was no
      significant difference in completion times between competent and noncompetent
      users except for the posterior branch (151 s:105 s; P = .01). The competent users
      had more efficient motion as evidenced by statistically significant differences
      in the metrics of motion analysis. Users with >20 hours of experience performed
      significantly better than those newer to the system, independent of prior
      endovascular experience. CONCLUSIONS: This study demonstrates that motion-based
      metrics can differentiate novice from trained users of flexible robotics systems
      for basic endovascular tasks. Efficiency of catheter movement, consistency of
      performance, and learning curves may help identify users who are sufficiently
      trained for safe clinical use of the system. This work will help identify the
      learning curve and specific movements that translate to expert robotic
      navigation.

PMID- 25619580
TI  - Debate: whether endovascular repair offers a survival advantage over open repair
      for ruptured abdominal aortic aneurysms.
AB  - During the last decade, new information and reports have been published regularly
      describing endovascular and open repair of ruptured abdominal aortic aneurysms,
      but despite this, disagreement persists over which therapy is best. At the root
      of the problem is the discrepancy between the findings of multiple well-performed
      observational studies and a smaller number of randomized controlled trials. Our
      debaters do an excellent job of summarizing the current status of the world
      literature and describing their conflicting interpretations. 

PMID- 25619581
TI  - Editors' commentary.

PMID- 25619582
TI  - Family history of aortic aneurysm is an independent risk factor for more rapid
      growth of small abdominal aortic aneurysms in Japan.

PMID- 25619583
TI  - Regarding "Comparison of treatment strategies for thoracic endograft infection".

PMID- 25619584
TI  - Reply: To PMID 25135872.

PMID- 25619585
TI  - Regarding "The influence of contralateral occlusion on results of carotid
      interventions from the Society for Vascular Surgery Vascular Registry".

PMID- 25619586
TI  - Female obesity and infertility.
AB  - Infertility affects one in seven couples, and its rate is on the increase.
      Ovulatory defects and unexplained causes account for >50% of infertile
      aetiologies. It is postulated that a significant proportion of these cases are
      either directly or indirectly related to obesity. The prevalence of overweight
      and obese men and women has topped 50% in some developed countries. Obesity is on
      the increase worldwide; in turn, the consequences in terms of the associated
      morbidity and mortality have also been increasing. Obesity is associated with
      various reproductive sequelae including anovulation, subfertility and
      infertility, increased risk of miscarriage and poor neonatal and maternal
      pregnancy outcomes. Thus, the combination of infertility and obesity poses some
      very real challenges in terms of both the short- and long-term management of
      these patients. The mechanism with which obesity impacts female reproductive
      function is summarised in this review. 

PMID- 25619587
TI  - Characterization of the in situ immunological responses to vaccine adjuvants.
AB  - Adjuvants are included with many inactivated and some modified live vaccines to
      enhance immune responses to specific antigens. While early vaccines relied
      exclusively upon aluminum salts, still the major adjuvant used in human vaccines,
      other adjuvant products are used in veterinary medicine. In addition to enhancing
      antigen presentation, adjuvants can also enhance the development of specific
      immune responses. Thus, alum adjuvants often preferentially stimulate humoral
      immune responses. By contrast, lipid-based adjuvants are often more effective at
      stimulating cell-mediated immune responses. Metastim((r)) is a lipid-based
      adjuvant reported to elicit both humoral and cellular immune responses, though
      the mechanism responsible for this activity remains unclear. In this study, we
      compared the ability of equine influenza virus vaccines containing either saline
      or Metastim((r)) or an aluminum phosphate adjuvant to stimulate antigen
      presenting cell function in vivo. Six ponies were intradermally inoculated with
      inactivated equine influenza (KY97) mixed with either adjuvant or saline.
      Multiple sites were injected so that biopsies could be collected at different
      times post injection. The 4mm punch biopsies were formalin-fixed, paraffin
      embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated
      from 2mm punch biopsies for the determination of gene expression by real-time
      PCR. H&E staining revealed a variety of cells recruited to the injection sites,
      including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR
      analysis of the injection site confirmed this cellular infiltration and
      identified increased expression of activation markers. Both vaccines also
      stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing
      Metastim((r)) elicited significantly higher gene expression of interferon-gamma,
      IL-12, CD4 and CD83 compared to alum (p<0.05). While the greater induction of
      IFNgamma-related gene expression indicates that Metastim((r)) can elicit Th-1
      immune responses more effectively than the aluminum salt, there was also evidence
      of Th2 cytokine induction.

PMID- 25619588
TI  - Soluble CD36 in plasma and urine: a plausible prognostic marker for diabetic
      nephropathy.
AB  - AIMS: This study was designed to analyze the level of soluble CD36 (sCD36) in
      both plasma and urine of type 2 diabetic patients with and without
      microalbuminuria/macroalbuminuria. METHODS: Study subjects (n=20 each) comprised
      of those with normal glucose tolerance, type 2 diabetes (T2DM) with
      normoalbuminiria, T2DM with microalbuminuria and T2DM with macroalbuminuria. The
      biochemical parameters were analyzed using auto-analyzer, and the level of sCD36
      was estimated using an in-house Sandwich ELISA. RESULTS: The presence of sCD36
      has been identified for the first time in the urine sample. Significant increase
      in the level of sCD36 was observed in both plasma and urine of diabetic patients
      with microalbuminuria (P<0.01) and macroalbuminuria (P<0.001). Positive
      correlation of sCD36 with the kidney markers such as urea, creatinine and eGFR
      confirmed the association of sCD36 with kidney damage in diabetic patients.
      Microalbuminuria, which is clinically used as a biomarker for nephropathy showed
      a strong positive correlation with urine sCD36 (r=0.642; P<0.001) and plasma
      sCD36 (r=0.498; P<0.001) in Pearson correlation analysis, which was further
      substantiated in stepwise multiple regression analysis. CONCLUSIONS: Our study
      implies a plausible prognostic/adjuvant biomarker role of soluble CD36 for
      diabetic nephropathy.

PMID- 25619589
TI  - The fate of siderophores: antagonistic environmental interactions in exudate
      mediated micronutrient uptake.
AB  - Organisms acquire metals from the environment by releasing small molecules that
      solubilize and promote their specific uptake. The best known example of this
      nutrient uptake strategy is the exudation of siderophores, which are a
      structurally-diverse class of molecules that are traditionally viewed as being
      integral to iron uptake. Siderophores have been proposed to act through a variety
      of processes, but their effectiveness can be mitigated by a variety of chemical
      and physical processes of both biotic and abiotic origin. Processes that occur at
      the surface of minerals can degrade or sequester siderophores, preventing them
      from fulfilling their function of returning metals to the organism. In addition,
      biotic processes including enzymatic degradation of the siderophore and piracy of
      the metal or of the siderophore complex also disrupt iron uptake. Some organisms
      have adapted their nutrient acquisition strategies to address these potential
      pitfalls, producing multiple siderophores and other exudates that take advantage
      of varying kinetic and thermodynamic factors to allow the continued uptake of
      metals. A complete understanding of the factors that contribute to metal uptake
      in nature will require a concerted effort to study processes identified in
      laboratory systems in the context of more complicated environmental systems. 

PMID- 25619590
TI  - Regulation of a maize HD-ZIP IV transcription factor by a non-conventional RDR2
      dependent small RNA.
AB  - Small non-coding RNAs are versatile riboregulators that control gene expression
      at the transcriptional or post-transcriptional level, governing many facets of
      plant development. Here we present evidence for the existence of a 24 nt small
      RNA (named small1) that is complementary to the 3' UTR of OCL1 (Outer Cell
      Layer1), the founding member of the maize HD-ZIP IV gene family encoding plant
      specific transcription factors that are mainly involved in epidermis
      differentiation and specialization. The biogenesis of small1 depends on DICER
      like 3 (DCL3), RNA-dependent RNA polymerase 2 (RDR2) and RNA polymerase IV,
      components that are usually required for RNA-dependent DNA-methylation.
      Unexpectedly, GFP sensor experiments in transient and stable transformation
      systems revealed that small1 may regulate its target at the post-transcriptional
      level, mainly through translational repression. This translational repression is
      attenuated in an rdr2 mutant background in which small1 does not accumulate. Our
      experiments further showed the possible involvement of a secondary stem-loop
      structure present in the 3' UTR of OCL1 for efficient target repression,
      suggesting the existence of several regulatory mechanisms affecting OCL1 mRNA
      stability and translation. 

PMID- 25619591
TI  - The phenotypic and molecular genetic spectrum of Alstrom syndrome in 44 Turkish
      kindreds and a literature review of Alstrom syndrome in Turkey.

PMID- 25619592
TI  - Simultaneous determination of six active components by a single standard to
      determine multicomponents combined with fingerprint analysis for the quality
      control of Rhizoma Chuanxiong.
AB  - To control the quality of Rhizoma Chuanxiong, a method based on high-performance
      liquid chromatography method coupled with diode array detection was developed for
      the quantitative analysis of six active ingredients using a single standard to
      determine multi-components and chemical fingerprint analysis for the first time.
      The separation was performed on an Agilent Zorbax SB-C18 column by gradient
      elution with methanol and aqueous phase (containing 0.5% glacial acetic acid) at
      a flow rate of 1.0 mL/min. The UV wavelength was set at 274 nm. This assay was
      fully validated with respect to precision, repeatability, and accuracy. All
      calibration curves showed good linearity (R(2) > 0.9994) within test ranges. The
      limit of detection and limit of quantification were lower than 0.01 and 0.03
      MUg/mL, respectively. The relative standard deviation for repeatability and the
      intermediate precision of six analytes were less than 1.6 and 2.5%, respectively,
      the overall recovery was 96.1-103.1%. In addition, fingerprint chromatography
      using hierarchical clustering analysis and similarity analysis was performed to
      differentiate and classify the samples. The method described here could provide a
      more comprehensive and reasonable scientific assessment of the quality of Rhizoma
      Chuanxiong. Therefore, the strategy is feasible, credible, and is easily and
      effectively adapted for evaluating the quality control of Rhizoma Chuanxiong. 

PMID- 25619593
TI  - Synthesis of pyrazines from rhodium-catalyzed reaction of 2H-Azirines with N
      sulfonyl 1,2,3-triazoles.
AB  - An efficient synthetic route to a wide range of trisubstituted pyrazines is
      developed from Rh-catalyzed reaction of 2H-azirines with N-sulfonyl-1,2,3
      triazoles through the elimination of nitrogen molecule and arylsulfinic acid. The
      present reaction proceeds through formation of in situ generated
      dihydropyrazines. 

PMID- 25619595
TI  - CCDC40 mutation as a cause of primary ciliary dyskinesia: a case report and
      review of literature.
AB  - BACKGROUND AND AIMS: Primary ciliary dyskinesia (PCD) is a rare, genetically
      heterogeneous disorder. Genetic defects affecting motility of cilia and flagella
      cause chronic destructive airway disease, situs inversus and, frequently, male
      infertility in PCD. To date, although several genes have been implicated in PCD,
      the genetic bases of most cases of PCD remain elusive. METHODS: By applying a
      whole-exome sequencing strategy, we reported a case of PCD carrying a novel
      mutant alleles in CCDC40 gene, and did literature review. RESULTS: A 36-year-old
      nonsmoking Chinese man suffered from chronic cough since childhood and an 8-year
      history of primary infertility. Lung biopsy showed respiratory bronchiolitis.
      Chest images showed bronchiectasis and situs inversus. Semen analysis showed high
      sperm counts and poor sperm motility. Transmission electron microscopy (TEM) of
      cilia cross-sections showed ultrastructural defects, including inner dynein arms
      (IDA) defect and axonemal disorganization. To identify gene mutations that cause
      PCD, we performed exome sequencing to analyze genome of this patient, and
      discovered a previously uncharacterized mutant alleles (NM_001243342.1:c.2609G>A;
      p. R870H) in CCDC40 gene. In addition, we summarize the PCD disease-causing genes
      and CCDC40 mutant sites based on current literature. CONCLUSIONS: We identified a
      novel mutant alleles in CCDC40 gene, which altered the protein sequence and
      resulted in the ultrastructural defects in the microtubule structure of cilia.
      Thereby, these defects lead to the patient with bronchiectasis, bronchiolitis and
      infertility.

PMID- 25619594
TI  - Asymmetric cell division in the Drosophila bristle lineage: from the polarization
      of sensory organ precursor cells to Notch-mediated binary fate decision.
AB  - Asymmetric cell division (ACD) is a simple and evolutionary conserved process
      whereby a mother divides to generate two daughter cells with distinct
      developmental potentials. This process can generate cell fate diversity during
      development. Fate asymmetry may result from the unequal segregation of molecules
      and/or organelles between the two daughter cells. Here, I will review how fate
      asymmetry is regulated in the sensory bristle lineage in Drosophila and focus on
      the molecular mechanisms underlying ACD of the sensory organ precursor cells
      (SOPs). For further resources related to this article, please visit the WIREs
      website.

PMID- 25619596
TI  - The first small-molecule inhibitors of members of the ribonuclease E family.
AB  - The Escherichia coli endoribonuclease RNase E is central to the processing and
      degradation of all types of RNA and as such is a pleotropic regulator of gene
      expression. It is essential for growth and was one of the first examples of an
      endonuclease that can recognise the 5'-monophosphorylated ends of RNA thereby
      increasing the efficiency of many cleavages. Homologues of RNase E can be found
      in many bacterial families including important pathogens, but no homologues have
      been identified in humans or animals. RNase E represents a potential target for
      the development of new antibiotics to combat the growing number of bacteria that
      are resistant to antibiotics in use currently. Potent small molecule inhibitors
      that bind the active site of essential enzymes are proving to be a source of
      potential drug leads and tools to dissect function through chemical genetics.
      Here we report the use of virtual high-throughput screening to obtain small
      molecules predicted to bind at sites in the N-terminal catalytic half of RNase E.
      We show that these compounds are able to bind with specificity and inhibit
      catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also
      inhibit the activity of RNase G, a paralogue of RNase E. 

PMID- 25619597
TI  - Impaired autophagy in hilar mossy cells of the dentate gyrus and its implication
      in schizophrenia.
AB  - Schizophrenia (SCZ) is a complex disease that has been regarded as a
      neurodevelopmental, synaptic or epigenetic disorder. Here we provide evidence
      that neurodegeneration is implicated in SCZ. The DTNBP1 (dystrobrevin-binding
      protein 1) gene encodes dysbindin-1 and is a leading susceptibility gene of SCZ.
      We previously reported that the dysbindin-1C isoform regulates the survival of
      the hilar glutamatergic mossy cells in the dentate gyrus, which controls the
      adult hippocampal neurogenesis. However, the underlying mechanism of hilar mossy
      cell loss in the dysbindin-1-deficient sandy (sdy) mice (a mouse model of SCZ) is
      unknown. In this study, we did not observe the apoptotic signals in the hilar
      mossy cells of the sdy mice by using the TUNEL assay and immunostaining of
      cleaved caspase-3 or necdin, a dysbindin-1- and p53-interacting protein required
      for neuronal survival. However, we found that the steady-state level of LC3-II, a
      marker of autophagosomes, was decreased in the hippocampal formation in the mice
      lacking dysbindin-1C. Furthermore, we observed a significant reduction of the
      cytosolic LC3-II puncta in the mossy cells of sdy mice. In addition,
      overexpression of dysbindin-1C, but not 1A, in cultured cells increased LC3-II
      level and the LC3 puncta in the transfected cells. These results suggest that
      dysbindin-1C deficiency causes impaired autophagy, which is likely implicated in
      the pathogenesis of SCZ. 

PMID- 25619598
TI  - EGFR/MAPK signaling regulates the proliferation of Drosophila renal and nephric
      stem cells.
AB  - Tissue homeostasis, accomplished through the self-renewal and differentiation of
      resident stem cells, is critical for the maintenance of adult tissues throughout
      an animal's lifetime. Adult Drosophila Malpighian tubules (MTs or fly kidney) are
      maintained by renal and nephric stem cells (RNSCs) via self-renewing divisions,
      however, it is unclear how RNSC proliferation and differentiation are regulated.
      Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but
      required for RNSC proliferation in vivo. Inactivation of the EGFR/MAPK pathway
      blocks or greatly retards RNSC cell cycle progression; conversely, over
      activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts
      the normal differentiation of renablasts (RBs), the immediate daughters of RNSC
      divisions. Our data further suggest that EGFR/MAPK signaling functions
      independently of JAK/STAT signaling and that dMyc and CycE partially mediate
      EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of
      EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important
      clues for understanding mammalian kidney repair and regeneration following
      injury. 

PMID- 25619599
TI  - TaSCL14, a novel wheat (Triticum aestivum L.) GRAS gene, regulates plant growth,
      photosynthesis, tolerance to photooxidative stress, and senescence.
AB  - Rates of photosynthesis, tolerance to photooxidative stress, and senescence are
      all important physiological factors that affect plant development and thus
      agricultural productivity. GRAS proteins play essential roles in plant growth and
      development as well as in plant responses to biotic and abiotic stresses. So far
      few GRAS genes in wheat (Triticum aestivum L.) have been characterized. A
      previous transcriptome analysis indicated that the expression of a GRAS gene
      (TaSCL14) was induced by high-light stress in Xiaoyan 54 (XY54), a common wheat
      cultivar with strong tolerance to high-light stress. In this study, TaSCL14 gene
      was isolated from XY54 and mapped on chromosome 4A. TaSCL14 was expressed in
      various wheat organs, with high levels in stems and roots. Our results confirmed
      that TaSCL14 expression was indeed responsive to high-light stress. Barley stripe
      mosaic virus (BSMV)-based virus-induced gene silencing (VIGS) of TaSCL14 in wheat
      was performed to help characterize its potential functions. Silencing of TaSCL14
      resulted in inhibited plant growth, decreased photosynthetic capacity, and
      reduced tolerance to photooxidative stress. In addition, silencing of TaSCL14 in
      wheat promoted leaf senescence induced by darkness. These results suggest that
      TaSCL14 may act as a multifunctional regulator involved in plant growth,
      photosynthesis, tolerance to photooxidative stress, and senescence. 

PMID- 25619600
TI  - Nocturnal to diurnal transition in the common ancestor of haplorrhines: evidence
      from genomic-scan for positively selected genes.

PMID- 25619601
TI  - Biolistic genetic transformation of a wide range of Chinese elite wheat (Triticum
      aestivum L.) varieties.

PMID- 25619602
TI  - First complete genome sequence of a probiotic Enterococcus faecium strain T-110
      and its comparative genome analysis with pathogenic and non-pathogenic
      Enterococcus faecium genomes.

PMID- 25619603
TI  - HIV and schistosomiasis in rural Zimbabwe: the association of retinol-binding
      protein with disease progression, inflammation and mortality.
AB  - BACKGROUND: Vitamin A has widespread effects on immune function and is therefore
      interesting in HIV-infection. Retinol-binding protein (RBP or RBP4) is a negative
      acute-phase protein and a marker of vitamin A status. Our aim was to investigate
      the association of RBP with HIV progression, infection with schistosomiasis,
      inflammatory cytokines, and mortality. METHODS: The study included 192 HIV
      infected and 177 HIV-uninfected individuals from Mupfure in rural Zimbabwe. Of
      these, 208 were infected with Schistosoma haematobium, 27 with S. mansoni and 48
      with both. Plasma RBP, HIV-RNA, CD4 cell count, haemoglobin, cytokines, clinical
      staging (CDC category), self-reported level of function (Karnoffsky Performance
      Score, KPS) and schistosomiasis status were assessed at baseline. Participants
      were followed up for survival 3-4 years post-enrolment. RESULTS: RBP levels were
      lower in HIV-infected individuals(p<0.0001). Among HIV-infected individuals,
      multivariable analysis showed RBP to be positively correlated with CD4 cell
      count(p=0.050), KPS(p=0.003), and haemoglobin(p<0.0001) and negatively correlated
      with HIV-RNA(p<0.0001), CDC category(p<0.0001), tumor necrosis factor-receptor
      II(p<0.0001) and interleukin(IL)-6(p=0.004), as well as with IL-8(p=0.005) and IL
      10(p=0.003) for HIV-infected men. Furthermore, among HIV-infected individuals RBP
      correlated negatively with schistosomiasis(p=0.038) and intensity of infection:
      circulating anodic antigen(p=0.014), circulating cathodic antigen(p<0.0001) and
      faecal egg output(p=0.004). CONCLUSIONS: In HIV-infected individuals, RBP was
      negatively associated with levels of inflammatory markers, markers of HIV
      progression, infection with schistosomiasis and markers of schistosomal
      intensity.

PMID- 25619604
TI  - Effects of soy beverage and soy-based formula on growth, weight, and fecal
      moisture: experimental study in rats.
AB  - OBJECTIVE: To compare body growth, weight, and fecal moisture in recently weaned
      rats fed exclusively on infant soy formula and soy-based beverage. METHODS: Three
      similar groups were formed (n=10/group) consisting of weanling Wistar rats,
      maintained in metabolic cages. One group was fed soy protein-based beverage,
      another with soy-based infant formula, and another with cow's milk infant formula
      (control group). Water and diet were offered ad libitum. Body weight and length
      were measured. Stool was collected for three consecutive days. RESULTS: Weight
      and length were lower (p = 0.001; p = 0.001) in the groups receiving soy protein
      based beverage (73.16 +/- 5.74 g; 23.94 +/- 1.04 cm) and soy-based formula (71.11
      +/- 5.84 g; 24.74 +/- 0.60 cm) in relation to the group receiving cow's milk
      formula (84.88 +/- 9.75 g; 26.01 +/- 0.91 cm). Fresh fecal weight was greater (p
      < 0.001) in the soy-based beverage (3.44 +/- 0.48 g) than in the soy-based
      formula (0.79 +/- 0.20 g) and cow's milk-based formula (0.42 +/- 0.17 g). Fecal
      moisture was higher (p < 0.001) in the group receiving soy protein-based beverage
      (47.28 +/- 9.02%) and soy-based formula (37.21 +/- 13.20%) than in the group
      receiving cow's milk formula (22.71 +/- 10.86%). CONCLUSION: The growth of rats
      fed soy protein-based beverage and soy-based formula was lower than those fed
      cow's milk-based formula. The soy protein-based beverage resulted in significant
      increase in fecal weight and moisture.

PMID- 25619605
TI  - Television viewing habits and their influence on physical activity and childhood
      overweight.
AB  - OBJECTIVES: To assess the prevalence of television (TV) viewing habits and their
      association with childhood sedentary lifestyle and overweight in 8-year-old
      children, from a cohort in a city in Southern Brazil. METHODS: A prospective
      cohort study with hospital screening of all births that occurred from September
      of 2002 to May of 2003. This study refers to a cross-sectional analysis of data
      collected during the cohort's follow-up conducted at 8 years of age. To evaluate
      the level of physical activity, a physical activity questionnaire for children
      and adolescents was used (PAQ-C), during the consultation at 8 years of age.
      RESULTS: Of the 616 interviewed children, a prevalence of sedentary lifestyle>70%
      was found, as well as the habit of watching TV for more than two hours a day in
      60% of the sample, regardless of gender (p=0.30), income (p=0.57), or family
      socioeconomic level (p=0.90). The daily time spent watching TV was inversely
      associated with physical activity (p<0.05) and positively associated with excess
      weight (p<0.01). Regarding physical activity, running was the most frequently
      practiced sports modality among the population. CONCLUSIONS: Considering the high
      prevalence of sedentary lifestyle and children who watch TV for an excessive
      period of time, it is necessary to motivate such individuals to perform
      interactive activities, as well as promote a more active lifestyle, by decreasing
      the time children spend in front of the TV.

PMID- 25619606
TI  - Fast-track pathway for reduction of dislocated hip arthroplasty reduces surgical
      delay and length of stay.
AB  - BACKGROUND AND PURPOSE: Dislocation is one of the most common complications
      following hip arthroplasty. Delay until reduction leads to pain for the patient,
      and may increase the risk of complications. We investigated the safety aspect of
      a fast-track pathway for dislocated hip arthroplasties and evaluated its effect
      on surgical delay and length of stay (LOS). PATIENTS AND METHODS: 402 consecutive
      and unselected dislocations (253 patients) were admitted at our institution
      between May 10, 2010 and September 31, 2013. The fast-track pathway for early
      reduction was introduced on January 9, 2011. Fast-track patients with a suspected
      dislocation (with no radiographic verification) were moved directly to the post
      anesthesia care unit and then straight to the operating room. Dislocation was
      confirmed under fluoroscopy with reduction under general anesthesia. Surgical
      delay (in hours), LOS (in hours), perioperative complications, and complications
      during the hospital stay were recorded. Dislocation status for fast-track
      patients (confirmed or unconfirmed by fluoroscopy) was also recorded. RESULTS:
      Both surgical delay (2.5 h vs. 4.1 h; p < 0.001) and LOS (26 h vs. 31 h; p <
      0.05) were less in patients admitted through the fast-track pathway than in
      patients on regular pathway. Perioperative complications (1.6% vs. 3.7%) and
      complications during the hospital stay (11% vs. 15%) were also less, but not
      statistically significantly so. Only 1 patient admitted through fast-track
      pathway had a fracture instead of a dislocation; all the other fast-track
      patients with suspected dislocation actually had dislocations. INTERPRETATION:
      The fast-track pathway for reduction of dislocated hip arthroplasty results in
      less surgical delay and in reduced LOS, without increasing perioperative
      complications or complications during the patient's stay.

PMID- 25619607
TI  - Conjugated polymer-porphyrin complexes for organic electronics.
AB  - We present the synthesis of novel conjugated polymer-porphyrin complexes for use
      in organic electronics. Linear and star-shaped platinated porphyrins were
      attached to regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT) arms to
      investigate whether porphyrin stacking and increased dimensionality can be used
      to control polymer morphology. The novel materials display similar optical
      properties to P3HT, but give higher mobilities when used in organic field-effect
      transistors. Atomic force microscopy measurements show that incorporation of only
      a small amount of porphyrin into the conjugated polymer backbone leads to
      increased aggregation. These materials demonstrate that polymer morphology and
      performance can be tuned and enhanced effectively through the use of
      conjugatively linked porphyrins. 

PMID- 25619608
TI  - Generic flux coupling analysis.
AB  - Flux coupling analysis (FCA) has become a useful tool for aiding metabolic
      reconstructions and guiding genetic manipulations. Originally, it was introduced
      for constraint-based models of metabolic networks that are based on the steady
      state assumption. Recently, we have shown that the steady-state assumption can be
      replaced by a weaker lattice-theoretic property related to the supports of
      metabolic fluxes. In this paper, we further extend our approach and develop an
      efficient algorithm for generic flux coupling analysis that works with any kind
      of qualitative pathway model. We illustrate our method by thermodynamic flux
      coupling analysis (tFCA), which allows studying steady-state metabolic models
      with loop-law thermodynamic constraints. These models do not satisfy the lattice
      theoretic properties required in our previous work. For a selection of genome
      scale metabolic network reconstructions, we discuss both theoretically and
      practically, how thermodynamic constraints strengthen the coupling results that
      can be obtained with classical FCA. A prototype implementation of tFCA is
      available at http://hoverboard.io/L4FC. 

PMID- 25619609
TI  - Synthesis and characterization of the rare-earth Dion-Jacobson layered
      perovskites, APrNb2O7 (A = Rb, Cs and CuCl).
AB  - The new double-layered perovskites, APrNb(2)O(7) (A = Rb, Cs) have been prepared
      by a high temperature ceramic method. Rietveld refinement of X-ray powder
      diffraction data confirmed the orthorhombic and tetragonal structures,
      respectively; RbPrNb(2)O(7) was refined in space group Imma (a = 5.4534(7) A, b =
      22.012(1) A, c = 5.4549(7) A) and CsPrNb(2)O(7) in P4/mmm (a = 3.8668(2) A, c =
      11.163(1) A). (CuCl)PrNb(2)O(7), topochemically prepared by replacement of
      Rb(+)/Cs(+) with CuCl(+), contains a 2D Cu-Cl network between the PrNb(2)O(7)
      slabs (orthorhombic space group Pbam, a = 7.7328(6) A, b = 7.7113(4) A and c =
      11.6706(3) A). The parent compounds both show paramagnetic behavior MU(eff) (Rb)
      = 3.34(1)MU(B) and MU(eff) (Cs) = 3.60(2)MU(B) while the (CuCl)PrNb(2)O(7),
      paramagnetic (MU(eff) = 4.020(8)MU(B)) down to 20 K, exhibits antiferromagnet
      like behavior below 20 K.

PMID- 25619611
TI  - Waterjet cutting of periprosthetic interface tissue in loosened hip prostheses:
      an in vitro feasibility study.
AB  - Waterjet cutting technology is considered a promising technology to be used for
      minimally invasive removal of interface tissue surrounding aseptically loose hip
      prostheses. The goal of this study was to investigate the feasibility of waterjet
      cutting of interface tissue membrane. Waterjets with 0.2 mm and 0.6 mm diameter,
      a stand-off distance of 5 mm, and a traverse speed of 0.5 mm/s were used to cut
      interface tissue samples in half. The water flow through the nozzle was
      controlled by means of a valve. By changing the flow, the resulting waterjet
      pressure was regulated. Tissue sample thickness and the required waterjet
      pressures were measured. Mean thickness of the samples tested within the 0.2 mm
      nozzle group was 2.3 mm (SD 0.7 mm) and within the 0.6 mm nozzle group 2.6 mm (SD
      0.9 mm). The required waterjet pressure to cut samples was between 10 and 12 MPa
      for the 0.2 mm nozzle and between 5 and 10 MPa for the 0.6 mm nozzle. Cutting
      bone or bone cement requires about 3 times higher waterjet pressure (30-50 MPa,
      depending on used nozzle diameter) and therefore we consider waterjet cutting as
      a safe technique to be used for minimally invasive interface tissue removal.

PMID- 25619612
TI  - Principal component analysis of atrial fibrillation: inclusion of posterior ECG
      leads does not improve correlation with left atrial activity.
AB  - BACKGROUND: Lead V1 is routinely analysed due to its large amplitude AF waveform.
      V1 correlates strongly with right atrial activity but only moderately with left
      atrial activity. Posterior lead V9 correlates strongest with left atrial
      activity. AIMS: (1) To establish whether surface dominant AF frequency (DAF)
      calculated using principal component analysis (PCA) of a modified 12-lead ECG
      (including posterior leads) has a stronger correlation with left atrial activity
      compared to the standard ECG. (2) To assess the contribution of individual ECG
      leads to the AF principal component in both ECG configurations. METHODS: Patients
      were assigned to modified or standard ECG groups. In the modified ECG, posterior
      leads V8 and V9 replaced V4 and V6. AF waveform was extracted from one-minute
      surface ECG recordings using PCA. Surface DAF was correlated with intracardiac
      DAF from the high right atrium (HRA), coronary sinus (CS) and pulmonary veins
      (PVs). RESULTS: 96 patients were studied. Surface DAF from the modified ECG did
      not have a stronger correlation with left atrial activity compared to the
      standard ECG. Both ECG configurations correlated strongly with HRA, CS and right
      PVs but only moderately with left PVs. V1 contributed most to the AF principal
      component in both ECG configurations.

PMID- 25619613
TI  - A robust real-time gait event detection using wireless gyroscope and its
      application on normal and altered gaits.
AB  - Gait events detection allows clinicians and biomechanics researchers to determine
      timing of gait events, to estimate duration of stance phase and swing phase and
      to segment gait data. It also aids biomedical engineers to improve the design of
      orthoses and FES (functional electrical stimulation) systems. In recent years,
      researchers have resorted to using gyroscopes to determine heel-strike (HS) and
      toe-off (TO) events in gait cycles. However, these methods are subjected to
      significant delays when implemented in real-time gait monitoring devices,
      orthoses, and FES systems. Therefore, the work presented in this paper proposes a
      method that addresses these delays, to ensure real-time gait event detection. The
      proposed algorithm combines the use of heuristics and zero-crossing method to
      identify HS and TO. Experiments involving: (1) normal walking; (2) walking with
      knee brace; and (3) walking with ankle brace for overground walking and treadmill
      walking were designed to verify and validate the identified HS and TO. The
      performance of the proposed method was compared against the established gait
      detection algorithms. It was observed that the proposed method produced detection
      rate that was comparable to earlier reported methods and recorded reduced time
      delays, at an average of 100 ms.

PMID- 25619614
TI  - An advanced compliance monitor for patients undergoing brace treatment for
      idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis is a spinal deformity affecting 2-3% of
      adolescents. Brace treatment, the most common non-surgical treatment, uses a hard
      plastic orthotic shell to prevent progression of the deformity. Previous studies
      have found association between treatment outcome and patients' compliance with
      the prescribed brace-wear regimen. However, the exact relationship between
      compliance and treatment outcome has yet to be elucidated. Current compliance
      monitoring techniques may not be providing enough information about patients'
      brace-wear habits. Building on previous work, we present a new compliance monitor
      which records both temperature and force applied to the patient's body. The
      combination of temperature and force readings shows both how often and how
      tightly the brace is worn. The new monitor is designed for minimal size and power
      consumption, measuring 5.2 cm * 2.5 cm * 0.8 cm, with a battery life of
      approximately one year. Seven patients wore the monitor in this pilot study. The
      temperature-based compliance estimate differed significantly from the force-based
      estimate in four out of seven cases. This suggests that some patients may wear
      their braces very loosely, and that existing temperature-only or force-only
      compliance monitors may not be giving a complete picture of brace-wear habits. 

PMID- 25619615
TI  - Quantitative evaluation of the pulmonary microdistribution of TiO2 nanoparticles
      using X-ray fluorescence microscopy after intratracheal administration with a
      microsprayer in rats.
AB  - The unevenness of pulmonary nanoparticle (NP) distribution, which hinders the
      establishment of an absolute dose-response relationship, has been described as
      one of the limitations of intratracheal administration techniques for
      toxicological assessment of inhaled NPs. Quantification of the NP
      microdistribution would facilitate the establishment of a concentration-response
      relationship in localized regions of the lung; however, such quantitative methods
      have not been reported. Here, we established a quantitative method for evaluating
      pulmonary TiO2 NP microdistribution in rats using X-ray fluorescence microscopy.
      Ti intensity in lung sections from rats intratracheally administered 10 mg kg(-1)
      TiO2 NPs with a microsprayer was measured using X-ray fluorescence with a 100 um
      beam size. Ti reference samples were prepared by dropping different
      concentrations of Ti solutions on glass slide or lung sections of untreated rat.
      Ti intensity increased linearly with Ti content in the reference samples on both
      substrates. The detection limit of TiO2 was estimated to be 6.3 ng mm(-2) . The
      reproducibility was confirmed for measurements done in the short- (2 weeks) and
      long-term (6 months). The quantitative results of TiO2 NP microdistribution
      suggested that more TiO2 NPs were distributed in the right caudal and accessory
      lobes, which are located downstream of the administration direction of the NP
      suspension, and the lower portion of each lobe. The detection rates of TiO2 NPs
      were 16.6-25.0%, 5.19-15.6%, 28.6-39.2%, 21.4-38.7% and 10.6-23.2% for lung
      sections from the right cranial, middle, caudal, accessory and left lobes,
      respectively.

PMID- 25619616
TI  - The late positive potential: a neural marker of the regulation of emotion-based
      approach-avoidance actions?
AB  - The ability to regulate our emotional responses is crucial to effective
      functioning in daily life. Whilst there has been extensive study of the brain
      potentials related to valenced stimuli, the neural basis of the ability to
      regulate actions elicited by these remains to be clarified. To address this, 40
      volunteers undertook an approach-avoidance paradigm. In the congruent condition,
      participants approached pleasant and avoided unpleasant stimuli. In the
      incongruent condition, the opposite was the case, requiring the regulation of
      natural emotional response tendencies. Both behavioural and electrophysiological
      indices of emotional regulation were recorded. Congruency effects were observed
      at both the behavioural and electrophysiological level. Reaction times were
      faster and the LPP larger, when performing emotionally congruous relative to
      incongruous actions. Moreover, neural and behavioural effects were correlated.
      The current results suggest that the LPP congruency effect can be considered a
      neural marker of individual differences in emotion-driven action tendencies. We
      discuss whether this reflects emotion regulation, effort allocation, or correct
      mapping of stimulus response tendencies. 

PMID- 25619617
TI  - The early visual encoding of a face (N170) is viewpoint-dependent: a parametric
      ERP-adaptation study.
AB  - Visual representations of faces are extracted shortly after 100 ms in the human
      brain, leading to an occipito-temporal cortex N170 event-related potential (ERP).
      To understand the nature of this early visual representation, a full-front
      adapting face preceded a different or identical target face identity. The target
      face varied parametrically in head orientation from the adapting face (0-90
      degrees , 15 degrees  steps). The N170 elicited by the target face increased
      progressively from 0 degrees  up to 30 degrees  head orientation, with no further
      increase until 90 degrees . The N170 decreased for repeated face identities, this
      effect being stable between 0 degrees  and 30 degrees  changes of viewpoint, and
      no effect beyond that angle. These observations suggest that a face is encoded in
      a view-dependent manner, being matched to either a full-front or a profile face
      view. Yet, individual face representations activated as early as the peak of the
      N170 generalize partially across views.

PMID- 25619619
TI  - Current Diabetes Reviews in its 11th year of publication.

PMID- 25619618
TI  - Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots.
AB  - BACKGROUND: Ultrasound accelerates tissue-type plasminogen activator (t-PA)
      induced fibrinolysis of clots in vitro and in vivo. OBJECTIVE: To identify
      mechanisms for the enhancement of t-PA-induced fibrinolysis of clots. METHODS:
      Turbidity is an accurate and convenient method, not previously used, to follow
      the effects of ultrasound. Deconvolution microscopy was used to determine changes
      in structure, while fluorescence recovery after photobleaching was used to
      characterize the kinetics of binding/unbinding and transport. RESULTS: The
      ultrasound pulse repetition frequency affected clot lysis times, but there were
      no thermal effects. Ultrasound in the absence of t-PA produced a slight but
      consistent decrease in turbidity, suggesting a decrease in fibrin diameter due
      solely to the action of the ultrasound, likely caused by an increase in
      protofibril tension because of vibration from ultrasound. Changes in fibrin
      network structure during lysis with ultrasound were visualized in real time by
      deconvolution microscopy, revealing that the network becomes unstable when 30-40%
      of the protein in the network was digested, whereas without ultrasound, the
      fibrin network was digested gradually and retained structural integrity.
      Fluorescence recovery after photobleaching during lysis revealed that the off
      rate of oligomers from digesting fibers was little affected, but the number of
      binding/unbinding sites was increased. CONCLUSIONS: Ultrasound causes a decrease
      in the diameter of the fibers due to tension as a result of vibration, leading to
      increased binding sites for plasmin(ogen)/t-PA. The positive feedback of this
      structural change together with increased mixing/transport of t-PA/plasmin(ogen)
      is likely to account for the observed enhancement of fibrinolysis by ultrasound.

PMID- 25619621
TI  - Characterizing prefrontal cortical activity during inhibition task in
      methamphetamine-associated psychosis versus schizophrenia: a multi-channel near
      infrared spectroscopy study.
AB  - Methamphetamine abuse and dependence, frequently accompanied by schizophrenia
      like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a
      serious public health problem worldwide. Few studies, however, have characterized
      brain dysfunction associated with MAP, nor investigated similarities and
      differences in brain dysfunction between MAP and schizophrenia. We compared
      prefrontal cortical activity associated with stop-signal inhibitory task in 21
      patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched
      healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system.
      Both the MAP and the schizophrenia groups showed significantly reduced activation
      in the bilateral ventrolateral prefrontal cortex compared with controls; however,
      only the MAP group showed reduced activation in the frontopolar prefrontal
      cortex. The MAP group demonstrated significant positive correlations between task
      performance and hemodynamic responses in the bilateral ventrolateral, polar and
      left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia
      groups demonstrated a significant difference in the relationship of impulsivity
      to hemodynamic changes in the bilateral premotor cortex. These findings
      characterize similarities and differences in prefrontal cortical dysfunction
      between psychosis associated with methamphetamine and schizophrenia. The reduced
      hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a
      common underlying pathophysiology of MAP and schizophrenia, whereas those in the
      frontopolar prefrontal cortex point to an impaired state that is either inherent
      or caused specifically by methamphetamine use. 

PMID- 25619622
TI  - Synthesis and Evaluation of a CBZ-AAN-Dox Prodrug and its in vitro Effects on
      SiHa Cervical Cancer Cells Under Hypoxic Conditions.
AB  - Although doxorubicin (Dox) is widely used in clinical treatment for solid tumors,
      it causes many side-effects such as heart and kidney damage, bone marrow
      suppression, and drug resistance. Legumain is a lysosomal protease that is
      elevated and associated with an invasive and metastatic phenotype in a number of
      solid tumors. In this study, we designed and synthesized a Dox prodrug, N
      benzyloxycarbonyl-Ala-Ala-Asn-Doxorubicin (CBZ-AAN-Dox), with 94% purity. Single
      substrate kinetic assays demonstrated hLegumain-specific enzymatic cleavage and
      activation of the prodrug in vitro, and this enzymatic cleavage of the prodrug
      substrate was more sensitive in acidic conditions, releasing more than 70% of Dox
      after 24 h. Treatment of tumor cells with our prodrug demonstrated a much higher
      IC50 value, significantly enhanced uptake of the prodrug, and considerably less
      cellular toxicity compared to Dox treatment alone. Our study presents a novel
      prodrug, CBZ-AAN-Dox, to potentially increase both the safety and efficacy of
      clinical treatment of tumors by exploiting the tumor's innate expression of
      legumain. 

PMID- 25619624
TI  - A comparative study of the characteristics of French fries produced by deep fat
      frying and air frying.
AB  - Air frying is being projected as an alternative to deep fat frying for producing
      snacks such as French fries. In air frying, the raw potato sections are
      essentially heated in hot air containing fine oil droplets, which dehydrates the
      potato and attempts to impart the characteristics of traditionally produced
      French fries, but with a substantially lower level of fat absorbed in the
      product. The aim of this research is to compare: (1) the process dynamics of air
      frying with conventional deep fat frying under otherwise similar operating
      conditions, and (2) the products formed by the 2 processes in terms of color,
      texture, microstructure, calorimetric properties, and sensory characteristics.
      Although, air frying produced products with a substantially lower fat content but
      with similar moisture contents and color characteristics, it required much longer
      processing times, typically 21 min in relation to 9 min in the case of deep fat
      frying. The slower evolution of temperature also resulted in lower rates of
      moisture loss and color development reactions. Differential scanning calorimetry
      (DSC) studies revealed that the extent of starch gelatinization was also lower in
      the case of air fried product. In addition, the 2 types of frying also resulted
      in products having significantly different texture and sensory characteristics. 

PMID- 25619623
TI  - Biodegradable micelles capable of mannose-mediated targeted drug delivery to
      cancer cells.
AB  - A targeted micellar drug delivery system is developed from a biocompatible and
      biodegradable amphiphilic polyester, poly(Lac-OCA)-b-(poly(Tyr(alkynyl)-OCA)-g
      mannose) (PLA-b-(PTA-g-mannose), that is synthesized via controlled ring-opening
      polymerization of O-carboxyanhydride (OCA) and highly efficient "Click"
      chemistry. Doxorubicin (DOX), a model lipophilic anticancer drug, can be
      effectively encapsulated into the micelles, and the mannose moiety allows active
      targeting of the micelles to cancer cells that specifically express mannose
      receptors, which thereafter enhances the anticancer efficiency of the drug.
      Comprised entirely of biodegradable and biocompatible polyesters, this micellar
      system demonstrates promising potentials for targeted drug delivery and cancer
      therapy. 

PMID- 25619625
TI  - Determination of sevoflurane and isopropyl alcohol in exhaled breath by thermal
      desorption gas chromatography-mass spectrometry for exposure assessment of
      hospital staff.
AB  - Volatile anaesthetics and disinfection chemicals pose ubiquitous inhalation and
      dermal exposure risks in hospital and clinic environments. This work demonstrates
      specific non-invasive breath biomonitoring methodology for assessing staff
      exposures to sevoflurane (SEV) anaesthetic, documenting its metabolite
      hexafluoroisopropanol (HFIP) and measuring exposures to isopropanol (IPA) dermal
      disinfection fluid. Methods are based on breath sample collection in Nalophan
      bags, followed by an aliquot transfer to adsorption tube, and subsequent analysis
      by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Ambient
      levels of IPA were also monitored. These methods could be generalized to other
      common volatile chemicals found in medical environments. Calibration curves were
      linear (r(2)=0.999) in the investigated ranges: 0.01-1000 ppbv for SEV, 0.02-1700
      ppbv for IPA, and 0.001-0.1 ppbv for HFIP. The instrumental detection limit was
      10 pptv for IPA and 5 pptv for SEV, both estimated by extracted ion-TIC
      chromatograms, whereas the HFIP minimum detectable concentration was 0.5 pptv as
      estimated in SIM acquisition mode. The methods were applied to hospital staff
      working in operating rooms and clinics for blood draws. SEV and HFIP were present
      in all subjects at concentrations in the range of 0.7-18, and 0.002-0.024 ppbv
      for SEV and HFIP respectively. Correlation between IPA ambient air and breath
      concentration confirmed the inhalation pathway of exposure (r=0.95, p<0.001) and
      breath-borne IPA was measured as high as 1500 ppbv. The methodology is easy to
      implement and valuable for screening exposures to common hospital chemicals.
      Although the overall exposures documented were generally below levels of health
      concern in this limited study, outliers were observed that indicate potential for
      acute exposures.

PMID- 25619626
TI  - Functional analysis of the GlcP promoter in Streptomyces peucetius var. caesius.
AB  - In Streptomyces, carbon utilization is of significant importance for the
      expression of genes involved in morphological differentiation and antibiotic
      production. Glucose is mainly transported by GlcP, a membrane protein encoded by
      glcp. In Streptomyces coelicolor, this protein is encoded by sco5578. However,
      there is little information about the physiology of the GlcP promoter in
      Streptomyces. The aim of the present work was to clone and perform a functional
      analysis of the sp7066 promoter (ortholog of sco5578) from Streptomyces peucetius
      var. caesius. Hydrophobicity and cellular location analysis of the putative amino
      acid sequence of the cloned gene predicted SP7066 would be a membrane protein
      with a topology of six plus six transmembrane segments interrupted by a large
      cytoplasmic loop. In silico analysis of the upstream region of the sp7066
      transcription initiation site predicted the sequences 5'-AGGAATAGT-3' and 5'
      TTGACT-3' for regions -10 and -35 of sp7066 promoter. To reflect sp7066
      expression, the promoter sequence was amplified, subcloned, and fused to the egfp
      reporter gene. Immunoblot analysis revealed that D-glucose and its analog 2
      deoxyglucose were able to induce sp7066 expression. This effect was not modified
      by the presence of equimolar concentrations of D-galactose or N
      acetylglucosamine. No expression of egfp was detected with the use of other
      carbon sources such as L-arabinose, D-fructose, and glycerol. Based on these
      analyses, we conclude that D-glucose is a preferred carbon source in S. peucetius
      var. caesius and that the sp7066 expression product, a putative non-PTS glucose
      permease, likely is a H+/symporter, localized to the membrane, and shows a strong
      specificity for D-glucose for inducing expression. 

PMID- 25619627
TI  - PhenoFluorMix: practical chemoselective deoxyfluorination of phenols.
AB  - A practical deoxyfluorination with novel deoxyfluorinating reagent PhenoFluorMix,
      a mixture of N,N'-1,3-bis(2,6-diisopropylphenyl)chloroimidazolium chloride and
      CsF, is presented. PhenoFluorMix overcomes the challenges associated with
      hydrolysis of PhenoFluor. PhenoFluorMix does not hydrolyze, is readily available
      on decagram scale, and is storable in air. In this paper, we demonstrate the
      practicality of the reagent and exhibit the deoxyfluorination of a variety of
      phenols and heterocycles. 

PMID- 25619628
TI  - Microencapsulation of probiotic bacteria Lactobacillus plantarum 15HN using
      alginate-psyllium-fenugreek polymeric blends.
AB  - AIMS: Investigation on the use of herbal-based biopolymers for probiotic
      Lactobacillus plantarum 15HN-encapsulation is presented. The objectives are to
      enhance its oral delivery, colonic release and survival rate of these probiotic
      cultures in gastrointestinal environment. METHODS AND RESULTS: Nine types of
      herbal-based polymers blend with different concentration of alginate alone or
      mixed with psyllium and fenugreek was used as candidate for encapsulation matrix
      by applying a simple extrusion method. All the blend formulations recorded high
      encapsulation efficiency at value >98%. The survival rate of viable probiotic
      cells under both low pH and high bile salt conditions was also high with value
      above 80% in 2% (w/v) alginate, alginate+psyllium (1.5 + 0.5%) blend and
      alginate+fenugreek (1.5 + 0.5%) blend as compared to other polymer formulations
      and nonencapsulated cells. Their release occurred after 2 h in colonic condition
      and sustained until the 12th hour incubation period. A value added prebiotic
      effect was observed in (1.5 + 0.5%) alginate-psyllium formulation. CONCLUSIONS:
      The high encapsulation efficiency, high viability of cell in low pH, high bile
      salt and the sustained release rates of probiotic cells in colonic condition
      during storage time was also observed for these herbal gel formulations.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Herbal-based biopolymers offer added
      advantages of being prebiotic towards the enhancement of probiotic bacterial
      growth in the gastrointestinal environment.

PMID- 25619629
TI  - Does systemic clarithromycin therapy have an inhibitory effect on
      tympanosclerosis? An experimental animal study.
AB  - OBJECTIVE: To demonstrate the inhibitory effects of clarithromycin on in vitro
      tympanosclerosis. METHOD: Twenty-eight rats were divided into three groups: a
      clarithromycin group, a non-clarithromycin group and a negative control group.
      Those in the first two groups were injected with Streptococcus pneumoniae
      following a myringotomy, and tympanosclerosis was experimentally induced. Oral
      clarithromycin therapy was administered in the clarithromycin group. The other
      groups received no medical treatment. RESULTS: All eardrums in the clarithromycin
      and non-clarithromycin groups developed myringosclerosis, but there was only one
      eardrum, in the clarithromycin group, with very severe myringosclerosis. In the
      clarithromycin group, 11 ears showed no inflammation and there were no ears with
      severe inflammation. In the non-clarithromycin group, there were 11 ears with
      severe inflammation. The mean eardrum thickness in the clarithromycin group was
      20.93 um and in the non-clarithromycin group it was 42.71 um. CONCLUSION: Acute
      otitis media and myringotomies induced tympanosclerosis, but clarithromycin
      reduced the severity of tympanosclerosis.

PMID- 25619631
TI  - Children in family foster care have greater health risks and less involvement in
      Child Health Services.
AB  - AIM: This study investigated the impact of being in family foster care on
      selected health determinants and participation in Child Health Services (CHS).
      METHODS: Two groups of 100 children, born between 1992 and 2008, were studied
      using data from Swedish Child Health Services for the preschool period up to the
      age of six. The first group had been in family foster care, and the controls,
      matched for age, sex and geographic location, had not. Descriptive statistics
      were used to describe differences in health determinants and participation in
      Child Health Services between the two groups. RESULTS: The foster care group had
      higher health risks, with lower rates of breastfeeding and higher levels of
      parental smoking. They were less likely to have received immunisations and
      attended key nurse or physician visits and speech and vision screening. Missing
      data for the phenylketonuria test were more common in children in family foster
      care. CONCLUSION: Children in family foster care were exposed to more health
      risks than the control children and had lower participation in the universal
      child health programme during the preschool period. These results call for secure
      access to high-quality preventive health care for this particularly vulnerable
      group of children.

PMID- 25619630
TI  - Spectrum of myeloid neoplasms and immune deficiency associated with germline
      GATA2 mutations.
AB  - Guanine-adenine-thymine-adenine 2 (GATA2) mutated disorders include the recently
      described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex
      infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial
      MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms),
      congenital neutropenia, congenital lymphedema (Emberger's syndrome),
      sensorineural deafness, viral warts, and a spectrum of aggressive infections seen
      across all age groups. While considerable efforts have been made to identify the
      mutations that characterize this disorder, pathogenesis remains a work in
      progress with less than 100 patients described in current literature. Varying
      clinical presentations offer diagnostic challenges. Allogeneic stem cell
      transplant remains the treatment of choice. Morbidity, mortality, and social
      costs due to the familial nature of the disease are considerable. We describe our
      experience with the disorder in three affected families and a comprehensive
      review of current literature. 

PMID- 25619632
TI  - The relationship between the spinopelvic balance and the incidence of adjacent
      vertebral fractures following percutaneous vertebroplasty.
AB  - We evaluated the relationship between sagittal spinopelvic parameters and the
      occurrence of adjacent vertebral fractures (AVF) and determined the possible risk
      factor. The most important factors for AVFs are the degree of osteoporosis and
      altered biomechanics due to the spinopelvic imbalance in the fractured area of
      the spine. INTRODUCTION: We intend to evaluate the relationship between sagittal
      spinopelvic parameters and the occurrence of adjacent vertebral fractures
      following the initial compression fracture and to determine the possible dominant
      risk factor associated with new compression fractures. METHODS: From March 2010
      to May 2012, 240 consecutive patients with painful vertebral compression
      fractures (VCFs) were enrolled in a retrospective study. Ninety-one patients with
      VCFs underwent percutaneous vertebroplasty (VP) at 112 levels. The sagittal
      vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope
      (SS), pelvic tilt (PT), pelvic incidence (PI), and segmental kyphotic angle on
      sagittal standing radiographs were used to evaluate radiologic outcomes. RESULTS:
      In 2 years, 15 out of 134 patients (11.1%) treated with conservative treatment,
      and 12 out of 91 patients (13.1%) treated with VP sustained adjacent level
      fracture. More patients with the BMD higher or equal to 3.0 experienced a new
      fracture than those with a BMD less than 3.0 (p = 0.019), and the risk for
      adjacent level fractures decreased significantly when segmental kyphotic angle
      was less than 11 degrees  (p = 0.001), SVA was less than 6 cm (p = 0.001), SS was
      higher or equal to 25 degrees  (p = 0.004), and LL was higher or equal to 25
      degrees  (p = 0.020). CONCLUSIONS: The most important factors for new VCFs after
      the initial compression fractures are the degree of osteoporosis and altered
      biomechanics due to the spinopelvic imbalance in the fractured area of the spine.
      Regarding the spinopelvic alignment to investigate the relationship with a
      subsequent AVF, segmental kyphotic angle, SS, LL, and SVA may be a potential
      predictor.

PMID- 25619633
TI  - Sex-specific differences in progressive glucose intolerance and hip geometry: the
      Baltimore Longitudinal Study of Aging.
AB  - Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre
      diabetes and T2DM on bone macroarchitecture and strength has not been well
      investigated. In this study, we show that in women only, both pre-diabetes and
      T2DM are associated with decreased hip bending strength and mineralization which
      might lead to skeletal weakness. INTRODUCTION: Older men and women with T2DM are
      at increased risk for fracture despite normal bone mineral density (BMD). The
      discordance between bone quantity and skeletal fragility has driven investigation
      into additional determinants of fracture resistance in T2DM. Additionally, the
      effect of pre-diabetes on bone strength has not been well described. The aim of
      this study was to determine differences in bone macroarchitecture and strength,
      measured by hip geometry, in persons with normal glucose tolerance (NGT),
      impaired glucose tolerance (IGT), and T2DM. METHODS: We performed cross-sectional
      analyses of older (age >55 years) men (n = 472) and women (n = 473) participating
      in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or
      T2DM based on oral glucose tolerance testing. Bone strength measures included the
      hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and
      buckling ratio (BR). Sex-stratified analyses were conducted using adjusted
      stepwise regression models. RESULTS: In women, IGT and T2DM were negatively
      associated with hip geometry parameters including mineralization in cross section
      (CSA, beta -0.076 and -0.073, respectively; both p < 0.05) and hip bending
      strength (Z, beta -0.097 and -0.09, respectively; both p < 0.05); conversely, IGT
      and T2DM were associated with improved compressive strength (BR, beta -0.31 and 
      0.29, respectively; both p < 0.05). There was no significant association between
      glycemic status and hip geometry in men. CONCLUSIONS: In women only, both IGT and
      T2DM were inversely associated with bone macroarchitecture and measures of bone
      mineralization and bending strength. The same association between worsening
      glycemic status and bone strength was not observed in men. These data suggest a
      differential effect of sex on hip geometry with evolving glucose intolerance.

PMID- 25619634
TI  - Improving adherence to and persistence with oral therapy of osteoporosis.
AB  - Osteoporosis treatment has low adherence and persistence. This study evaluated if
      greater patient involvement could improve them. At 12 months, only 114 out of 344
      participants were "fully adherent and persistent" (all drug doses taken
      throughout the study). Only frequency of drug administration had a significant
      influence on adherence. INTRODUCTION: Osteoporosis affects millions of
      individuals worldwide. There are now several effective drugs, but adherence to
      and persistence with treatment are low. This 12-month multicenter, prospective,
      randomized study evaluated the efficacy of two different methods aimed at
      improving adherence and persistence through greater patient involvement, compared
      with standard clinical practice. METHODS: Three hundred thirty-four post
      menopausal women, receiving an oral prescription for osteoporosis for the first
      time, were recruited and randomized into three groups: group 1 (controls, managed
      according to standard clinical practice) and groups 2 and 3 (managed with greater
      patient and caregiver involvement and special reinforcements: group 2, instructed
      to use several different "reminders"; group 3, same "reminders" as group 2, plus
      regular phone calls from and meetings at the referring Center). All enrolled
      women had two visits (baseline and 12 months). RESULTS: Of 334 enrolled women,
      247 (74%) started the prescribed therapy. Of those who started, 219 (88.7%)
      persisted in therapy for at least 10 months. At final evaluation, only 114 women
      were considered as "fully adherent and persistent" (all doses taken throughout
      the 12 months). There were no significant differences regarding "full adherence"
      among the three randomized groups. The frequency of drug administration had a
      significant influence: weekly administration had a >5-fold higher adherence and
      monthly administration an 8-fold higher adherence (p < 0.0001) than daily
      administration. CONCLUSIONS: The special effort of devising and providing
      additional reminders did not prove effective. Additional interventions during the
      follow-up, including costly interventions such as phone calls and educational
      meetings, did not provide significant advantages.

PMID- 25619635
TI  - Design, synthesis and pharmacological evaluation of N-[4-(4
      (alkyl/aryl/heteroaryl)-piperazin-1-yl)-phenyl]-carbamic acid ethyl ester
      derivatives as novel anticonvulsant agents.
AB  - A series of alkyl/aryl/heteroaryl piperazine derivatives (37-54) were designed
      and synthesized as potential anticonvulsant agents. The target compounds are
      endowed with satisfactory physicochemical as well as pharmacokinetic properties.
      The synthesized compounds were screened for their in vivo anticonvulsant activity
      in maximal electroshock (MES) and subcutaneous pentylenetetrazole (sc-PTZ)
      seizure tests. Further, neurotoxicity evaluation was carried out using rotarod
      method. Structure activity relationship studies showed that compounds possessing
      aromatic group at the piperazine ring displayed potent anticonvulsant activity.
      Majority of the compounds showed anti-MES activity whereas compounds 39, 41, 42,
      43, 44, 50, 52, and 53 exhibited anticonvulsant activity in both seizure tests.
      All the compounds except 42, 46, 47, and 50 did not show neurotoxicity. The most
      active derivative, 45 demonstrated potent anticonvulsant activity in MES test at
      the dose of 30mg/kg (0.5h) and 100mg/kg (4h) and also delivered excellent
      protection in sc-PTZ test (100mg/kg) at both time intervals. Therefore, compound
      45 was further assessed in PTZ-kindling model of epilepsy which is widely used
      model for studying epileptogenesis. This compound was effective in delaying onset
      of PTZ-evoked seizures at the dose of 5mg/kg in kindled animals and significantly
      reduced oxidative stress better than standard drug phenobarbital (PB). In result,
      compound 45 emerged as a most potent and safer anticonvulsant lead molecule. 

PMID- 25619636
TI  - Computer-aided identification of novel anticancer compounds with a possible dual
      HER1/HER2 inhibition mechanism.
AB  - HER1 and HER2 are frequently overexpressed in human tumors where they drive
      cellular proliferation. For this reason they are considered important targets in
      anticancer therapy with dual HER1/HER2 inhibitors being recently approved and
      marketed. In this paper we report the identification of a series of compounds
      with anticancer activity by a combined virtual screening approach on the kinase
      domains of HER1 and HER2. 6 hit compounds that present a sub- or low-micromolar
      activity in two cell-based assays, were initially identified and a subsequent
      design cycle led to the synthesis of a compound with nanomolar activity in the
      cell-based assays. 

PMID- 25619637
TI  - Quantification of proteins using (13)C7-labeled and unlabeled iodoacetanilide by
      nano liquid chromatography/nanoelectrospray ionization and by selected reaction
      monitoring mass spectrometry.
AB  - The combination of cysteine-specific modifiers, iodoacetanilide (IAA) and (13)C7
      labeled iodoacetanilide ((13)C7-IAA), has been applied to absolute quantification
      of proteins. The selected reaction monitoring (SRM) with the use of nano liquid
      chromatography/nanoelectrospray ionization ion trap mass spectrometry (nano
      LC/nano-ESI-IT-MS) analysis was applied to precise quantification of three
      commercial proteins. Good correlation was observed between the theoretical ratios
      and observed ratios for all these proteins both in a simple buffer solution and
      in a complex protein environment. Due to efficient tagging, this method does not
      require separate synthesis of isotope-labeled peptides for the SRM studies.
      Therefore, this method is expected to be a useful tool for proteomics research. 

PMID- 25619638
TI  - Synthesis of oolongtheanins and their inhibitory activity on micellar cholesterol
      solubility in vitro.
AB  - The synthesis of oolongtheanins (1a-d) was accomplished from EGC and/or EGCg in
      three steps. Oolongtheanin-3'-O-gallate (1b) showed more potent inhibitory
      activity on micellar cholesterol solubility than did EGCg. 

PMID- 25619639
TI  - Graphene/enzyme-encrusted three-dimensional carbon micropillar arrays for
      mediatorless micro-biofuel cells.
AB  - Two-dimensional graphene is a promising candidate material for use in high
      performance enzymatic biofuel cells (EBFCs). In this work, graphene/enzyme has
      been integrated onto three-dimensional (3D) micropillar arrays in order to obtain
      efficient enzyme immobilisation and enhanced enzyme loading and facilitate direct
      electron transfer. The fabrication process of this system combines top-down
      carbon microelectromechanical systems (C-MEMS) to fabricate the 3D micropillar
      array platform and bottom-up electrophoretic deposition (EPD) to deposit the
      graphene/enzyme onto the electrode surface. The amperometric response of the
      graphene-based bioelectrode exhibited excellent electrochemical activity, which
      indicated the successful co-deposition of graphene with the enzymes. The
      developed 3D graphene/enzyme network-based EBFC generated a maximum power density
      of 136.3 MUW cm(-2) at 0.59 V, which is almost seven times the maximum power
      density of the bare 3D carbon micropillar array-based EBFC. 

PMID- 25619640
TI  - 6-Shogaol enhances renal carcinoma Caki cells to TRAIL-induced apoptosis through
      reactive oxygen species-mediated cytochrome c release and down-regulation of c
      FLIP(L) expression.
AB  - 6-Shogaol, a potent bioactive compound in ginger (Zingiber officinale Roscoe),
      has been reported for anti-inflammatory and anti-cancer activity. In this study,
      we investigated the effect of 6-shogaol to enhance tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The combined treatment with
      6-shogaol and TRAIL markedly induces apoptosis in various cancer cells (renal
      carcinoma Caki cells, breast carcinoma MDA-MB-231 cells and glioma U118MG cells),
      but not in normal mesangial cells and normal mouse kidney cells. 6-Shogaol
      reduced the mitochondrial membrane potential (MMP) and released cytochrome c from
      mitochondria to cytosol via Bax activation. Furthermore, we found that 6-shogaol
      induced down-regulation of c-FLIP(L) expression at the post-translational levels
      and the overexpression of c-FLIP(L) markedly inhibited 6-shogaol plus TRAIL
      induced apoptosis. Moreover, 6-shogaol increased reactive oxygen species (ROS)
      production in Caki cells. Pretreatment with ROS scavengers attenuated 6-shogaol
      plus TRAIL-induced apoptosis through inhibition of MMP reduction and down
      regulation of c-FLIP(L) expression. In addition, 6-gingerol, another phenolic
      alkanone isolated from ginger, did not enhance TRAIL-induced apoptosis and down
      regulate c-FLIP(L) expression. Taken together, our results demonstrated that 6
      shogaol enhances TRAIL-mediated apoptosis in renal carcinoma Caki cells via ROS
      mediated cytochrome c release and down-regulation of c-FLIP(L) expression. 

PMID- 25619641
TI  - Plasma lipidomics reveal profound perturbation of glycerophospholipids, fatty
      acids, and sphingolipids in diet-induced hyperlipidemia.
AB  - Hyperlipidemia is a major risk factor for coronary heart disease and has emerged
      as an important public health problem. Lipidomics is a powerful technology for
      assessment of global lipid metabolites in a biological system and for biomarker
      discovery. In the present study, hyperlipidemia was induced by feeding rats a
      high fat diet. A sensitive ultra-performance liquid chromatography coupled with
      quadrupole time-of-flight synapt high-definition mass spectrometry method was
      used for the analysis of plasma lipids. Orthogonal partial least squares
      discriminant analysis, correlation analysis and heatmap analysis were performed
      to investigate the metabolic changes in rats with diet-induced hyperlipidemia.
      Potential biomarkers were detected using S-plot and were identified by accurate
      mass data, isotopic pattern and MS(E) fragments information. Significantly
      increased total cholesterol, triglycerides and low-density lipoprotein
      cholesterol as well as decreased high-density lipoprotein cholesterol were
      observed in diet-induced hyperlipidemic rats. Combined with standard serum
      biochemical results, significant differences in plasma lipid compounds including
      eleven glycerophospholipids, six fatty acids, two sphingolipids, one eicosanoid,
      one sterol lipid and one glycerolipid were observed, highlighting the
      perturbation of lipid metabolism in diet-induced hyperlipidemia. These findings
      provide further insights into the lipid profile across a wide range of
      biochemical pathways in diet-induced hyperlipidemia. 

PMID- 25619642
TI  - Xanthine oxidase inhibitory properties and anti-inflammatory activity of 2-amino
      5-alkylidene-thiazol-4-ones.
AB  - Thirty 2-amino-5-alkylidene-thiazol-4-ones were assayed for inhibitory activity
      against commercial enzyme xanthine oxidase (XO) in vitro and XO in rat liver
      homogenate as well as for anti-inflammatory response on human peripheral blood
      mononuclear cells (PBMCs). 4-((2-Benzylamino-4-oxothiazol-5(4H)-ylidene)
      methyl)benzonitrile showed the most potent inhibitory effect against commercial
      XO (IC50 = 17.16 MUg/mL) as well as against rat liver XO (IC50 = 24.50 MUg/mL).
      All compounds containing the 4-cyanobenzylidene group or (indol-3-yl)methylene
      group at the position 5 of thiazol-4-one moiety were moderately potent inhibitors
      of commercial XO. The assayed compounds were docked into the crystal structures
      of XO enzyme complexes with three diverse inhibitors (PDB codes: 1FIQ, 1VDV, and
      1V97) using OEDocking software. Our results strongly point to a correlation
      between the data on inhibitory activity against commercial XO and data on
      antioxidant activity of studied compounds, screened using a lipid peroxidation
      (LP) method. 2-(Benzylamino)-5-((thiophen-2-yl)methylene)thiazol-4(5H)-one showed
      the highest anti-inflammatory response on PBMCs, exerted most probably through
      the NF-kappaB inhibition. Studied 2-amino-5-alkylidene-thiazol-4-ones obey the
      "Rule of five" and meet all criteria for good solubility and permeability.

PMID- 25619643
TI  - Human prostaglandin reductase 1 (PGR1): Substrate specificity, inhibitor analysis
      and site-directed mutagenesis.
AB  - Prostaglandins (PGs) are lipid compounds derived from arachidonic acid by the
      action of cyclooxygenases, acting locally as messenger molecules in a wide
      variety of physiological processes, such as inflammation, cell survival,
      apoptosis, smooth muscle contraction, adipocyte differentiation, vasodilation and
      platelet aggregation inhibition. In the inactivating pathway of PGs, the first
      metabolic intermediates are 15-keto-PGs, which are further converted into 13,14
      dihydro-15-keto-PGs by different enzymes having 15-keto-PG reductase activity.
      Three human PG reductases (PGR), zinc-independent members of the medium-chain
      dehydrogenase/reductase (MDR) superfamily, perform the first irreversible step of
      the degradation pathway. We have focused on the characterization of the
      recombinant human enzyme prostaglandin reductase 1 (PGR1), also known as
      leukotriene B4 dehydrogenase. Only a partial characterization of this enzyme,
      isolated from human placenta, had been previously reported. In the present work,
      we have developed a new HPLC-based method for the determination of the 15-keto-PG
      reductase activity. We have performed an extensive kinetic characterization of
      PGR1, which catalyzes the NADPH-dependent reduction of the alpha,beta-double bond
      of aliphatic and aromatic aldehydes and ketones, and 15-keto-PGs. PGR1 also shows
      low activity in the oxidation of leukotriene B4. The best substrates in terms of
      kcat/Km were 15-keto-PGE2, trans-3-nonen-2-one and trans-2-decenal. Molecular
      docking simulations, based on the three-dimensional structure of the human enzyme
      (PDB ID 2Y05), and site-directed mutagenesis studies were performed to pinpoint
      important structural determinants, highlighting the role of Arg56 and Tyr245 in
      15-keto-PG binding. Finally, inhibition analysis was done using non-steroidal
      anti-inflammatory drugs (NSAIDs) as potential inhibitors. 

PMID- 25619645
TI  - Determination of phase stability of elemental boron.
AB  - Boron is an important element, used in applications from superhard materials to
      superconductors. Boron exists in several forms (allotropes) and, surprisingly, it
      was not known which form (alpha or beta) is stable at ambient conditions. Through
      experiment, we quantify the relative stability of alpha-boron and beta-boron as a
      function of temperature. The ground-state energies of alpha-boron and beta-boron
      are nearly identical. For all temperatures up to 2000 K, the complicated beta
      boron structure is more stable than the simpler alpha-boron structure at ambient
      pressure. Below 1000 K, beta-boron is entropically stabilized with respect to
      alpha-boron owing to its partially occupied sites, whereas at higher temperatures
      beta-boron is enthalpically stabilized with respect to alpha-boron. We show that
      alpha-boron only becomes stable on application of pressure. 

PMID- 25619646
TI  - Sexual and contraceptive behavior among female university students in Sweden -
      repeated surveys over a 25-year period.
AB  - OBJECTIVE: To study female students' sexual and contraceptive behavior and
      compare these results with earlier surveys. DESIGN: Comparative, repeated cross
      sectional surveys, started in 1989 and repeated every fifth year. SETTING:
      Contraceptive counseling delivered at a Student Health Center in Sweden.
      POPULATION: Female university students (n = 359). METHODS: Multiple-choice
      waiting-room questionnaire. MAIN OUTCOME MEASURES: Sexual and contraceptive
      behavior. RESULTS: In 1989, age at first intercourse was 17.6 years vs. 16.7
      years in 2014, number of lifetime sexual partners was 4.0 vs. 12.1 in 2014, and
      number of sexual partners during the previous 12 months was 1.0 vs. 2.8 in 2014.
      Condom use during first intercourse with the latest partner decreased from 49% to
      41% (n = 172 in 2009 vs. n = 148 in 2014: p < 0.001), and experience of anal sex
      increased from 39% to 46% (n = 136 in 2009 vs. n = 165 in 2014: p = 0.038), and
      25% (n = 41 in 2014) always used a condom during anal sex. A total of 70% (n =
      251) made use of pornography, and 48% (n = 121) considered their sexual behavior
      affected by pornography. Eighty-nine percent (n = 291) wanted two to three
      children and 9% (n = 33) had thought about freezing eggs for the future. The
      female students' knowledge about increasing age being correlated with decreased
      fertility varied. CONCLUSIONS: Sexual behavior among female university students
      has gradually changed during the last 25 years and behavior appears more risky
      today. As this may have consequences on future reproductive health, it is vital
      to inform women about consistent and correct condom use and about the limitations
      of the fertile window.

PMID- 25619644
TI  - Making quantitative morphological variation from basic developmental processes:
      Where are we? The case of the Drosophila wing.
AB  - One of the aims of evolutionary developmental biology is to discover the
      developmental origins of morphological variation. The discipline has mainly
      focused on qualitative morphological differences (e.g., presence or absence of a
      structure) between species. Studies addressing subtle, quantitative variation are
      less common. The Drosophila wing is a model for the study of development and
      evolution, making it suitable to investigate the developmental mechanisms
      underlying the subtle quantitative morphological variation observed in nature.
      Previous reviews have focused on the processes involved in wing differentiation,
      patterning and growth. Here, we investigate what is known about how the wing
      achieves its final shape, and what variation in development is capable of
      generating the variation in wing shape observed in nature. Three major
      developmental stages need to be considered: larval development, pupariation, and
      pupal development. The major cellular processes involved in the determination of
      tissue size and shape are cell proliferation, cell death, oriented cell division
      and oriented cell intercalation. We review how variation in temporal and spatial
      distribution of growth and transcription factors affects these cellular
      mechanisms, which in turn affects wing shape. We then discuss which aspects of
      the wing morphological variation are predictable on the basis of these
      mechanisms. Developmental Dynamics 244:1058-1073, 2015. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25619647
TI  - Is lower zone mediastinal nodal dissection always mandatory for lung cancer in
      the lower lobe?
AB  - PURPOSE: Dissection of the lower zone mediastinal nodes is mandatory during
      systematic nodal dissection for lung cancer. However, the significance of lower
      zone lymph node metastasis (LZM) in lung cancer remains unclear. Therefore, we
      aimed to identify the predictive factors for LZM in patients with lower lobe lung
      cancer. METHODS: A retrospective study was conducted on 257 patients with lower
      lobe lung cancer, in whom pulmonary resection and mediastinal nodal dissection
      were performed between 2009 and 2013. The radiological factors on thin-section
      computed tomography scans (TSCT) and several conventional clinical factors were
      evaluated as possible predictors of LZM. RESULTS: Twenty (7.8 %) patients
      exhibited LZM. The majority of the tumors were especially located in segment 10
      (50 %). All patients showed a solid appearance on TSCT. In a univariate analysis,
      the tumor location, a solid appearance and the clinical T factor significantly
      predicted LZM (p = 0.011, 0.005, 0.018). Furthermore, based on a multivariate
      analysis, the tumor location in segment 10 significantly predicted LZM in
      patients with lower lobe solid lung cancer (p = 0.031). CONCLUSION: The
      appropriate surgical strategy for lower zone lymph node dissection should be
      selected based on the tumor location and the findings of TSCT, due to the high
      frequency of LZM (19.6 %), especially in patients with pure solid lung cancer in
      segment 10.

PMID- 25619648
TI  - Zebrafish Rnf111 is encoded by multiple transcripts and is required for epiboly
      progression and prechordal plate development.
AB  - Arkadia (also known as RING finger 111) encodes a nuclear E3 ubiquitin ligase
      that targets intracellular effectors and modulators of TGFbeta/Nodal-related
      signaling for polyubiquitination and proteasome-dependent degradation. In the
      mouse, loss of Arkadia results in early embryonic lethality, with defects
      attributed to compromised Nodal signaling. Here, we report the isolation of
      zebrafish arkadia/rnf111, which is represented by 5 transcript variants.
      arkadia/rnf111 is broadly expressed during the blastula and gastrula stages, with
      eventual enrichment in the anterior mesendoderm, including the prechordal plate.
      Morpholino knockdown experiments reveal an unexpected role for Arkadia/Rnf111 in
      both early blastula organization and epiboly progression. Using a splice junction
      morpholino, we present additional evidence that arkadia/rnf111 transcript
      variants containing a 3' alternative exon are specifically required for epiboly
      progression in the late gastrula. This result suggests that arkadia/rnf111
      transcript variants encode functionally relevant protein isoforms that provide
      additional intracellular flexibility and regulation to the Nodal signaling
      pathway. 

PMID- 25619649
TI  - Is tolvaptan indicated for refractory oedema in nephrotic syndrome?
AB  - Tolvaptan is useful for correcting dilutional hyponatraemia because of its
      aquaretic effect. On the other hand, there is a distinct lack of data regarding
      tolvaptan-induced natriuresis, although previous studies have demonstrated
      improvement of congestive symptoms and signs in heart failure patients following
      tolvaptan treatment. Here, we report the case of a 47-year-old man diagnosed with
      minimal change nephrotic syndrome and whose refractory oedema was immediately
      controlled by tolvaptan before steroid response was induced. With tolvaptan
      treatment, patient urine output increased dramatically to approximately 5.5 L/day
      and body weight decreased by 9 kg over 5 days. Interestingly, urine sodium
      concentration, fractional excretion of sodium and urine osmolality all increased
      in response to tolvaptan administration. However, serum sodium concentration was
      maintained within the normal range, and mild azotaemia was corrected. Tolvaptan
      was discontinued after 11 days when heavy proteinuria and generalized oedema had
      been resolved. We discuss the potential mechanisms by which V2 receptor
      antagonists may stimulate natriuresis in the kidney. In conclusion, tolvaptan may
      be useful as an adjunctive treatment for oedematous disorders. 

PMID- 25619650
TI  - Is renal tissue oxygen desaturation during severe hypoxia underestimated? An
      observational study in term newborn piglets.
AB  - The kidney is an organ highly susceptible to injury by regional tissue oxygen
      desaturation during hypoxic episodes. Transcutaneous monitoring of renal tissue
      oxygen saturation is therefore of increasing interest. The aim of the present
      study was to compare renal tissue oxygen saturation measured by near-infrared
      spectroscopy (NIRS) during acute hypoxia in neonates directly on the kidney and
      transcutaneously. We hypothesized that transcutaneous renal tissue oxygen
      saturation measurements would be influenced by superficial tissue. Five term
      newborn piglets were anesthetized, instrumented and exposed to normocapnic
      hypoxia at an inspired oxygen concentration of 0.14. Regional tissue oxygen
      saturation (rSO2) was simultaneously measured for comparison with the sensor of
      NIRS (Invos 5100, Somanetics Corp., Troy, MI, USA) applied directly on the left
      kidney (renaldirect rSO2) and on the skin of right flank above the right kidney
      (renalskin rSO2). Cerebral regional tissue oxygenation (cerebralskin rSO2),
      arterial oxygen saturation, heart rate (HR) and mean arterial pressure (MAP) were
      also monitored. NIRS parameters were analyzed in 5 s intervals during first 2 min
      of hypoxia. Hypoxia was achieved with an arterial oxygen desaturation from median
      (range) 95.3% (86.8-98.0) to 23.5% (13.0-41.0) after 2 min. HR and MAP did not
      change significantly during hypoxia. There were pronounced and lower renaldirect
      rSO2 readings when compared with those of renalskin rSO2 with significant
      differences from 25 to 55 s after initiation of hypoxia. Changes of cerebralskin
      rSO2 and renalskin rSO2 were similar. Transcutaneous monitoring of renal tissue
      oxygen saturation may underestimate acute oxygen desaturation of the kidney
      during hypoxia in neonates.

PMID- 25619651
TI  - Is there a role for intervention in the management of atherosclerotic renal
      artery stenosis?

PMID- 25619652
TI  - Stress, burnout, and job satisfaction in 470 health professionals in 98 apheresis
      units in Italy: A SIdEM collaborative study.
AB  - AIMS: In Italian and international background, there are no studies focusing on
      stress, burnout indicators, and job satisfaction in health professionals working
      in the apheresis units. This study aims to fill this void both for scientific and
      clinical reasons. METHODS: The participants were 470 health professionals (220
      physicians, 250 nurses), mostly female (73.4%), with an average age of 48.09
      (with the 5 degrees  percentile under 32 years and the 95 degrees  percentile
      over 60), working in the Apheresis Units in the North (228), in the Center (131)
      and in the Southern-islands of Italy (111). The health professionals' years on
      the job were principally between one and 10 years (40.2%) or from 11 to 20 years
      (33.2%). The prevalent activity was therapeutic apheresis (48.5%). The self
      report questionnaires were proposed electronically by a protected online site.
      RESULTS: Important stress levels were identified in the health professionals.
      Physicians principally showed medium (47.5%) and high (35.8%) stress levels.
      Stress levels of nurses were mostly low (57.7%) or medium (25.7%). Female gender
      in nurses [t(268) = -3.29; P = 0.001] and in physician professions [t(217) = 
      3.01; P = 0.03] was a risk factor for stress. Both job categories were placed at
      a high risk level for burnout syndrome comparing with normative scales,
      especially the health professionals working in the center of Italy for the scales
      "Emotional exhaustion" [F(2) = 4.39; P = 0.013] and "Professional inefficacy"
      [F(2) = 4.38; P = 0.013]. CONCLUSIONS: Health professionals working in the
      apheresis unit show high stress levels and burnout risk. New preventive programs
      and specific clinical interventions should be constructed.

PMID- 25619653
TI  - IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and
      worsening cognitive behavior.
AB  - Anti-inflammatory strategies are proposed to have beneficial effects in
      Alzheimer's disease. To explore how anti-inflammatory cytokine signaling affects
      Abeta pathology, we investigated the effects of adeno-associated virus (AAV2/1)
      mediated expression of Interleukin (IL)-10 in the brains of APP transgenic mouse
      models. IL-10 expression resulted in increased Abeta accumulation and impaired
      memory in APP mice. A focused transcriptome analysis revealed changes consistent
      with enhanced IL-10 signaling and increased ApoE expression in IL-10-expressing
      APP mice. ApoE protein was selectively increased in the plaque-associated
      insoluble cellular fraction, likely because of direct interaction with aggregated
      Abeta in the IL-10-expressing APP mice. Ex vivo studies also show that IL-10 and
      ApoE can individually impair glial Abeta phagocytosis. Our observations that IL
      10 has an unexpected negative effect on Abeta proteostasis and cognition in APP
      mouse models demonstrate the complex interplay between innate immunity and
      proteostasis in neurodegenerative diseases, an interaction we call
      immunoproteostasis.

PMID- 25619654
TI  - Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology.
AB  - The impact of inflammation suppressor pathways on Alzheimer's disease (AD)
      evolution remains poorly understood. Human genetic evidence suggests involvement
      of the cardinal anti-inflammatory cytokine, interleukin-10 (IL10). We crossed the
      APP/PS1 mouse model of cerebral amyloidosis with a mouse deficient in Il10
      (APP/PS1(+)Il10(-/-)). Quantitative in silico 3D modeling revealed activated
      Abeta phagocytic microglia in APP/PS1(+)Il10(-/-) mice that restricted cerebral
      amyloidosis. Genome-wide RNA sequencing of APP/PS1(+)Il10(-/-) brains showed
      selective modulation of innate immune genes that drive neuroinflammation. Il10
      deficiency preserved synaptic integrity and mitigated cognitive disturbance in
      APP/PS1 mice. In vitro knockdown of microglial Il10-Stat3 signaling endorsed
      Abeta phagocytosis, while exogenous IL-10 had the converse effect. Il10
      deficiency also partially overcame inhibition of microglial Abeta uptake by human
      Apolipoprotein E. Finally, the IL-10 signaling pathway was abnormally elevated in
      AD patient brains. Our results suggest that "rebalancing" innate immunity by
      blocking the IL-10 anti-inflammatory response may be therapeutically relevant for
      AD.

PMID- 25619655
TI  - Simultaneous encoding of odors by channels with diverse sensitivity to
      inhibition.
AB  - Odorant receptors in the periphery map precisely onto olfactory glomeruli
      ("coding channels") in the brain. However, the odor tuning of a glomerulus is not
      strongly correlated with its spatial position. This raises the question of
      whether lateral inhibition between glomeruli is specific or nonspecific. Here we
      show that, in the Drosophila brain, focal activation of even a single glomerulus
      recruits GABAergic interneurons in all glomeruli. Moreover, the relative level of
      interneuron activity in different glomeruli is largely odor invariant. Although
      interneurons are recruited nonspecifically, glomeruli differ dramatically in
      their sensitivity to interneuron activity, and this is explained by their varying
      sensitivity to GABA. Interestingly, a stimulus is typically encoded in parallel
      by channels having high and low sensitivity to inhibition. Because lateral
      inhibition confers both costs and benefits, the brain might rely preferentially
      on "high" and "low" channels in different behavioral contexts. 

PMID- 25619656
TI  - Local postsynaptic voltage-gated sodium channel activation in dendritic spines of
      olfactory bulb granule cells.
AB  - Neuronal dendritic spines have been speculated to function as independent
      computational units, yet evidence for active electrical computation in spines is
      scarce. Here we show that strictly local voltage-gated sodium channel (Nav)
      activation can occur during excitatory postsynaptic potentials in the spines of
      olfactory bulb granule cells, which we mimic and detect via combined two-photon
      uncaging of glutamate and calcium imaging in conjunction with whole-cell
      recordings. We find that local Nav activation boosts calcium entry into spines
      through high-voltage-activated calcium channels and accelerates postsynaptic
      somatic depolarization, without affecting NMDA receptor-mediated signaling.
      Hence, Nav-mediated boosting promotes rapid output from the reciprocal granule
      cell spine onto the lateral mitral cell dendrite and thus can speed up recurrent
      inhibition. This striking example of electrical compartmentalization both adds to
      the understanding of olfactory network processing and broadens the general view
      of spine function.

PMID- 25619657
TI  - Orbitofrontal cortex uses distinct codes for different choice attributes in
      decisions motivated by curiosity.
AB  - Decision makers are curious and consequently value advance information about
      future events. We made use of this fact to test competing theories of value
      representation in area 13 of orbitofrontal cortex (OFC). In a new task, we found
      that monkeys reliably sacrificed primary reward (water) to view advance
      information about gamble outcomes. While monkeys integrated information value
      with primary reward value to make their decisions, OFC neurons had no systematic
      tendency to integrate these variables, instead encoding them in orthogonal
      manners. These results suggest that the predominant role of the OFC is to encode
      variables relevant for learning, attention, and decision making, rather than
      integrating them into a single scale of value. They also suggest that OFC may be
      placed at a relatively early stage in the hierarchy of information-seeking
      decisions, before evaluation is complete. Thus, our results delineate a circuit
      for information-seeking decisions and suggest a neural basis for curiosity.

PMID- 25619658
TI  - Neural population tuning links visual cortical anatomy to human visual
      perception.
AB  - The anatomy of cerebral cortex is characterized by two genetically independent
      variables, cortical thickness and cortical surface area, that jointly determine
      cortical volume. It remains unclear how cortical anatomy might influence neural
      response properties and whether such influences would have behavioral
      consequences. Here, we report that thickness and surface area of human early
      visual cortices exert opposite influences on neural population tuning with
      behavioral consequences for perceptual acuity. We found that visual cortical
      thickness correlated negatively with the sharpness of neural population tuning
      and the accuracy of perceptual discrimination at different visual field
      positions. In contrast, visual cortical surface area correlated positively with
      neural population tuning sharpness and perceptual discrimination accuracy. Our
      findings reveal a central role for neural population tuning in linking visual
      cortical anatomy to visual perception and suggest that a perceptually
      advantageous visual cortex is a thinned one with an enlarged surface area.

PMID- 25619659
TI  - High salt intake increases blood pressure via BDNF-mediated downregulation of
      KCC2 and impaired baroreflex inhibition of vasopressin neurons.
AB  - The mechanisms by which dietary salt promotes hypertension are unknown. Previous
      work established that plasma [Na(+)] and osmolality rise in proportion with salt
      intake and thus promote release of vasopressin (VP) from the neurohypophysis.
      Although high levels of circulating VP can increase blood pressure, this effect
      is normally prevented by a potent GABAergic inhibition of VP neurons by aortic
      baroreceptors. Here we show that chronic high salt intake impairs baroreceptor
      inhibition of rat VP neurons through a brain-derived neurotrophic factor (BDNF)
      dependent activation of TrkB receptors and downregulation of KCC2 expression,
      which prevents inhibitory GABAergic signaling. We show that high salt intake
      increases the spontaneous firing rate of VP neurons in vivo and that circulating
      VP contributes significantly to the elevation of arterial pressure under these
      conditions. These results provide the first demonstration that dietary salt can
      affect blood pressure through neurotrophin-induced plasticity in a central
      homeostatic circuit.

PMID- 25619660
TI  - Striatal long noncoding RNA Abhd11os is neuroprotective against an N-terminal
      fragment of mutant huntingtin in vivo.
AB  - A large number of gene products that are enriched in the striatum have ill
      defined functions, although they may have key roles in age-dependent
      neurodegenerative diseases affecting the striatum, especially Huntington disease
      (HD). In the present study, we focused on Abhd11os, (called ABHD11-AS1 in human)
      which is a putative long noncoding RNA (lncRNA) whose expression is enriched in
      the mouse striatum. We confirm that despite the presence of 2 small open reading
      frames (ORFs) in its sequence, Abhd11os is not translated into a detectable
      peptide in living cells. We demonstrate that Abhd11os levels are markedly reduced
      in different mouse models of HD. We performed in vivo experiments in mice using
      lentiviral vectors encoding either Abhd11os or a small hairpin RNA targeting
      Abhd11os. Results show that Abhd11os overexpression produces neuroprotection
      against an N-terminal fragment of mutant huntingtin, whereas Abhd11os knockdown
      is protoxic. These novel results indicate that the loss lncRNA Abhd11os likely
      contribute to striatal vulnerability in HD. Our study emphasizes that lncRNA may
      play crucial roles in neurodegenerative diseases.

PMID- 25619661
TI  - Tau immunization: a cautionary tale?
AB  - The amyloid beta (Abeta)-protein and microtubule-associated protein, tau, are the
      major components of the amyloid plaques and neurofibrillary tangles that typify
      Alzheimer's disease (AD) pathology. As such both Abeta and tau have long been
      proposed as therapeutic targets. Immunotherapy, particularly targeting Abeta, is
      currently the most advanced clinical strategy for treating AD. However, several
      Abeta-directed clinical trials have failed, and there is concern that targeting
      this protein may not be useful. In contrast, there is a growing optimism that tau
      immunotherapy may prove more efficacious. Here, for the first time, we studied
      the effects of chronic administration of an anti-tau monoclonal antibody (5E2) in
      amyloid precursor protein transgenic mice. For our animal model, we chose the J20
      mouse line because prior studies had shown that the cognitive deficits in these
      mice require expression of tau. Despite the fact that 5E2 was present and active
      in the brains of immunized mice and that this antibody appeared to engage with
      extracellular tau, 5E2-treatment did not recover age-dependent spatial reference
      memory deficits. These results indicate that the memory impairment evident in J20
      mice is unlikely to be mediated by a form of extracellular tau recognized by 5E2.
      In addition to the lack of positive effect of anti-tau immunotherapy, we also
      documented a significant increase in mortality among J20 mice that received 5E2.
      Because both the J20 mice used here and tau transgenic mice used in prior tau
      immunotherapy trials are imperfect models of AD our results recommend extensive
      preclinical testing of anti-tau antibody-based therapies using multiple mouse
      models and a variety of different anti-tau antibodies. 

PMID- 25619662
TI  - L-type calcium channel blockers and substance P induce angiogenesis of cortical
      vessels associated with beta-amyloid plaques in an Alzheimer mouse model.
AB  - It is well established that L-type calcium channels (LTCCs) are expressed in
      astroglia. However, their functional role is still speculative, especially under
      pathologic conditions. We recently showed that the alpha1 subunit-like
      immunoreactivity of the CaV1.2 channel is strongly expressed in reactive
      astrocytes around beta-amyloid plaques in 11-month-old Alzheimer transgenic (tg)
      mice with the amyloid precursor protein London and Swedish mutations. The aim of
      the present study was to examine the cellular expression of all LTCC subunits
      around beta-amyloid plaques by in situ hybridization using (35)S-labeled
      oligonucleotides. Our data show that messenger RNAs (mRNAs) of the LTCC CaV1.2
      alpha1 subunit as well as all auxiliary beta and alpha2delta subunits, except
      alpha2delta-4, were expressed in the hippocampus of age-matched wild-type mice.
      It was unexpected to see, that cells directly located in the plaque core in the
      cortex expressed mRNAs for CaV1.2 alpha1, beta2, beta4, and alpha2delta-1,
      whereas no expression was detected in the halo. Furthermore, cells in the plaque
      core also expressed preprotachykinin-A mRNA, the precursor for substance P. By
      means of confocal microscopy, we demonstrated that collagen-IV-stained brain
      vessels in the cortex were associated with the plaque core and were
      immunoreactive for substance P. In cortical organotypic brain slices of adult
      Alzheimer mice, we could demonstrate that LTCC blockers increased angiogenesis,
      which was further potentiated by substance P. In conclusion, our data show that
      brain vessels associated with beta-amyloid plaques express substance P and an
      LTCC and may play a role in angiogenesis. 

PMID- 25619663
TI  - Cognitive reserve modulates ERPs associated with verbal working memory in healthy
      younger and older adults.
AB  - Although many epidemiological studies suggest the beneficial effects of higher
      cognitive reserve (CR) in reducing age-related cognitive decline and dementia
      risk, the neural basis of CR is poorly understood. To our knowledge, the present
      study represents the first electrophysiological investigation of the relationship
      between CR and neural reserve (i.e., neural efficiency and capacity).
      Specifically, we examined whether CR modulates event-related potentials
      associated with performance on a verbal recognition memory task with 3 set sizes
      (1, 4, or 7 letters) in healthy younger and older adults. Neural data showed that
      as task difficulty increased, the amplitude of the parietal P3b component during
      the probe phase decreased and its latency increased. Notably, the degree of these
      neural changes was negatively correlated with CR in both age groups, such that
      individuals with higher CR showed smaller changes in P3b amplitude and less
      slowing in P3b latency (i.e., smaller changes in the speed of neural processing)
      with increasing task difficulty, suggesting greater neural efficiency. These CR
      related differences in neural efficiency may underlie reserve against
      neuropathology and age-related burden. 

PMID- 25619664
TI  - Aspiration dynamics in structured population acts as if in a well-mixed one.
AB  - Understanding the evolution of human interactive behaviors is important. Recent
      experimental results suggest that human cooperation in spatial structured
      population is not enhanced as predicted in previous works, when payoff-dependent
      imitation updating rules are used. This constraint opens up an avenue to shed
      light on how humans update their strategies in real life. Studies via simulations
      show that, instead of comparison rules, self-evaluation driven updating rules may
      explain why spatial structure does not alter the evolutionary outcome. Though
      inspiring, there is a lack of theoretical result to show the existence of such
      evolutionary updating rule. Here we study the aspiration dynamics, and show that
      it does not alter the evolutionary outcome in various population structures.
      Under weak selection, by analytical approximation, we find that the favored
      strategy in regular graphs is invariant. Further, we show that this is because
      the criterion under which a strategy is favored is the same as that of a well
      mixed population. By simulation, we show that this holds for random networks.
      Although how humans update their strategies is an open question to be studied,
      our results provide a theoretical foundation of the updating rules that may
      capture the real human updating rules. 

PMID- 25619665
TI  - Relationship between choroidal blood flow velocity and choroidal thickness during
      systemic corticosteroid therapy for Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To investigate the relationship between circulation hemodynamics and
      morphology in the choroid during systemic corticosteroid therapy for patients
      with Vogt-Koyanagi-Harada (VKH) disease. METHODS: This retrospective case series
      includes 18 eyes of nine patients with VKH disease (two men and seven women;
      average age, 40.8 years) who received systemic corticosteroid therapy. Laser
      speckle flowgraphy (LSFG) and enhanced-depth imaging optical coherence tomography
      (EDI-OCT) were performed before treatment and at 1 week and 1 and 3 months after
      treatment. The average values of the mean blur rate (MBR) at the macula and the
      central choroidal thickness (CCT) were compared at each stage. RESULTS: The
      changing rates of the average MBR significantly increased at all examinations
      after the start of treatment compared with the pre-treatment value with
      resolution of serous retinal detachment (SRD) (P = 0.0002 for all). The CCT
      decreased significantly at all examinations after the start of treatment compared
      with the pre-treatment value (P = 0.0002 for all). Changes in MBR and CCT during
      the 3-month follow-up period correlated significantly (R = -0.5913, P = 0.0097).
      The best-corrected visual acuity at pre-treatment correlated significantly with
      the changing rate of the MBR from 0 to 3 months (R = 0.5944, P = 0.0093) but not
      with CCT. CONCLUSIONS: Our data suggest that circulatory disturbances and
      increased thickness of the choroid relate to the pathogenesis of VKH disease with
      link mutually. LSFG is useful as an index for evaluating the choroiditis activity
      of VKH disease as well as EDI-OCT.

PMID- 25619666
TI  - Conjunctival amyloidosis -- clinical and histopathologic features.
AB  - PURPOSE: Conjunctival amyloidosis is a rare disorder. It is often clinically not
      suspected or diagnosed. This study intended to demonstrate the clinical and
      histopathologic features of this infrequent disease, including an
      immunohistochemical search for amyloidotic proteins. METHODS: Retrospective case
      series of the clinical and histopathologic characteristics of six patients with
      conjunctival amyloidosis. Immunohistochemical analysis with respect to possible
      amyloidotic components of the conjunctival deposits was performed. RESULTS: The
      diagnosis of amyloidosis was not suspected in all six cases presenting with an
      amelanotic conjunctival lesion. In three patients a conjunctival tumor of unknown
      origin, in one case each a papillomatous alteration of the conjunctiva, a
      conjunctival granulomatous inflammation, and a lymphoma were assumed
      respectively. The diagnosis of amyloidosis was made by histopathology.
      Immunohistochemical examination found lambda and kappa light chains as well as
      prealbumin within the amyloid deposits in one of the six specimens. CONCLUSIONS:
      The diagnosis of amyloidosis has to be kept in mind in cases with an unclear
      conjunctival mass or inflammatory process. Only a tissue biopsy is able to prove
      the diagnosis. A possible underlying systemic disease has to be ruled out.

PMID- 25619667
TI  - The natural history of polypoidal choroidal vasculopathy: a multi-center series
      of untreated Asian patients.
AB  - PURPOSE: We aimed to evaluate the long-term natural history of polypoidal
      choroidal vasculopathy (PCV) in untreated patients. METHODS: This is a
      retrospective observational case series. Patients with symptomatic PCV who did
      not receive any treatment for at least 12 months were included from the records
      of three ophthalmic clinics in Asia. The medical records and imaging data were
      reviewed. Visual outcomes at month 12 and at last follow-up were analyzed. The
      influence of demographics and presenting features on visual outcome was analyzed.
      RESULTS: A total of 32 eyes (32 patients) were included in this analysis. The
      mean follow-up was 59.9 months (range, 18-119 months), the mean age was 65.7
      years and 21 (65.6 %) patients were male. The mean presenting logMAR visual
      acuity was 0.79 (Standard deviation [SD] 0.49). The center of the fovea was
      involved by the PCV complex in 25 eyes (78.1 %). The mean greatest linear
      dimension (GLD) of the PCV complex was 2584 MUm (SD 880). Twenty-three eyes (71.9
      %) had a cluster-of-grapes configuration on indocyanine green angiography.
      Leakage of fluorescein angiography was present in 29 eyes (90.6 %). The mean
      logMAR vision deteriorated from 0.79 at baseline to 0.88 at month 12 (p = 0.11),
      and further to 1.14 (p = 0.003) at the last follow-up. The proportion of eyes
      that improved, remained unchanged and worsened was 21.9 %, 31.3 % and 46.9 %,
      respectively, at month 12; and 28.1 %, 9.4 % and 62.5 %, respectively, at last
      follow-up. The proportion of eyes with logMAR vision worse than 1.0 was 28.1 % at
      presentation, and increased to 31.3 % at month 12 and further to 53.1 % at last
      follow-up. Reasons for poor vision were due to retinal, subretinal or vitreous
      hemorrhage, and retinal pigment epithelium (RPE) atrophy and scarring. None of
      the presenting features were found to significantly influence visual outcome.
      CONCLUSIONS: Half of eyes presenting with symptomatic PCV had a relatively benign
      course without treatment and some even had vision improvement. However, in the
      remaining eyes, vision deteriorated significantly, mainly due to hemorrhage and
      scarring. There may be subtypes of PCV with divergent natural history.

PMID- 25619669
TI  - Psychiatric care of deaf patients in the general hospital: an overview.
AB  - BACKGROUND: While the number of Deaf and hard-of-hearing patients worldwide is
      estimated at six hundred million, few specialized psychiatric services or
      training resources exist to support the provision of mental health care to this
      population. This presents a particularly acute problem in the general hospital,
      where the consultant psychiatrist is likely to be confronted with the challenges
      of providing comprehensive psychiatric evaluation, diagnosis and treatment to
      patients with whom he or she may have limited experience or confidence. METHOD:
      We review critical considerations in the work-up, differential diagnosis, and
      management of commonly-presenting psychiatric disorders among Deaf patients in
      the general hospital setting.

PMID- 25619668
TI  - Outcomes of phacoemulsification in patients with chronic ocular graft-versus-host
      disease.
AB  - PURPOSE: The purpose of this study was to evaluate the outcomes of
      phacoemulsification in patients with ocular graft-versus-host disease (GVHD).
      METHODS: The occurrence of cataracts, cataract surgery, and its outcomes were
      analyzed in the medical records of 229 patients (458 eyes) with ocular GVHD.
      Outcome measures included pre- and postoperative corrected distance visual acuity
      (CDVA) and the rate of postoperative complications. RESULTS: Of the 458 eyes
      evaluated, 58 were pseudophakic; from the 400 phakic eyes, 238 (59 %) presented
      with cataracts and 62 (26 %) underwent cataract surgery. Analysis of
      postoperative complications and visual outcomes at 1 month was performed in 51
      eyes in which detailed surgical and immediate postoperative records were
      available. Preoperatively, the mean CDVA was 0.67 +/- 0.57 LogMAR (Snellen
      20/93), improving postoperatively to 0.17 +/- 0.18 (Snellen 20/29) at 1 month (P
      < 0.0001), and to 0.13 +/- 0.14 (Snellen 20/26) by the final follow-up visit (P <
      0.0001). Postoperative complications included corneal epithelial defects (8 %),
      filamentary keratitis (6 %), worsening of corneal epitheliopathy (16 %),
      posterior capsular opacification (18 %), and cystoid macular edema (4 %). A
      corrected distance visual acuity of 20/30 or better was achieved in 87 % of the
      eyes; suboptimal CDVA improvement was attributable to severe ocular surface
      disease, pre-existing advanced glaucoma, and prior macular surgery. CONCLUSIONS:
      Phacoemulsification in patients with chronic ocular GVHD is a safe and
      efficacious procedure resulting in significant visual improvement. Overall,
      postoperative adverse events responded well to timely management.

PMID- 25619670
TI  - Neuropsychiatric scurvy.
AB  - BACKGROUND: Scurvy is a disease with well-known peripheral symptoms, such as
      bleeding and pain. METHODS: The clinical and historical evidence for a distinct
      form of scurvy affecting the central nervous system, called neuropsychiatric
      scurvy, is reviewed. Pathophysiologic factors are described, as well as its
      diagnosis and management.

PMID- 25619671
TI  - Risk factors for alcohol relapse following orthotopic liver transplantation: a
      systematic review.
AB  - BACKGROUND: Each year, 5000-6000 individuals undergo orthotopic liver
      transplantation (OLT) in the United States, and of these, nearly 18% have
      alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients
      with OLT for alcoholic liver disease. OBJECTIVES: We sought to identify factors
      that predict relapse to alcohol or medication nonadherence following OLT in
      patients with alcoholic liver disease and to review what randomized clinical
      interventions have addressed these factors following OLT. Our hypothesis was that
      there would be factors before and after OLT that predict relapse to alcohol
      following OLT, and that these, if targeted, might improve sobriety and associated
      outcomes of adherence with medications and appointments. METHODS: We performed a
      review (focusing on articles published since 2004) with PubMed and MEDLINE
      searches using the following search terms: liver transplantation, recidivism,
      alcohol relapse, and predictors of alcohol relapse. We supplemented the online
      searches with manual reviews of article reference lists and selected relevant
      articles for further review by author consensus. RESULTS: In largely white
      populations, prospective studies document that shorter length of
      pretransplantation sobriety is a significant predictor of time to first drink and
      time to binge use. Presence of psychiatric comorbidity, high score on
      standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and
      Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are
      predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use
      history variables (e.g., family history of alcoholism) reliably discriminate
      between complete abstainers and those who drink, while medical and psychosocial
      characteristics at early post-liver transplantation period (e.g., more bodily
      pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with
      early-onset, rapidly accelerating moderate use and early-onset, continuously
      increasing heavy use have more than double the prevalence of steatohepatitis or
      rejection on biopsy and graft failure and more frequent mortality resulting from
      recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest
      drinking at 6y posttransplantation) alcohol users do. Fortunately,
      pretransplantation screening combined with a structured pretransplantation
      management program and a 12-step program attendance reduced recidivism. No
      randomized clinical trials have been performed that target pretransplantation
      risk factors in individuals with alcoholic liver disease before or after OLT to
      improve post-OLT outcomes. CONCLUSIONS: Recent research findings suggest that
      screening can reveal individuals who are vulnerable to alcohol relapse and
      targeted intervention can prevent their relapse to alcohol. Based on existing
      addiction treatments (e.g., relapse prevention plan construction), randomized
      clinical trials tailored to post-OLT patients should be conducted to improve
      their survival and quality of life.

PMID- 25619672
TI  - Citalopram, QTc Prolongation, and Torsades de Pointes.
AB  - OBJECTIVES: The aim of this systematic review is to identify case reports of
      citalopram use resulting in QTc prolongation, torsades de pointes, or both, in
      the medical literature. METHODS: A literature search was conducted of PubMed,
      MEDLINE, EMBASE, Scopus, and PsycINFO databases for case reports published in any
      language that reported the relationship between citalopram use and the
      development of QTc prolongation or torsades de pointes or both. In addition,
      bibliographic databases of published articles were searched for additional cases.
      RESULTS: A total of 18 case reports of citalopram use resulting in QTc
      prolongation were identified. Of these, 10 cases were also associated with the
      development of torsades de pointes. A total of 14 cases occurred in women and 4
      in men. There were 7 cases involving an overdose with citalopram. Of the 18
      cases, 12 occurred in individuals who were aged <60 years and 6 were in
      individuals aged >60 years. In 8 of the 18 cases, the individuals were taking a
      dose between 20 and 60mg of citalopram in a day. Hypertension was the most common
      comorbid medical condition, as seen in 5 of the cases. CONCLUSIONS: QTc
      prolongation or torsades de pointes are infrequently reported adverse effects
      associated with citalopram use.

PMID- 25619673
TI  - Thoughts of death and self-harm in patients with epilepsy or multiple sclerosis
      in a tertiary care center.
AB  - BACKGROUND: Patients with epilepsy or multiple sclerosis (MS) have high risks of
      depression and increased risks of suicide, but little is known about their risks
      of suicidal ideation. OBJECTIVE: We sought to (1) estimate the prevalence of
      thoughts of being better off dead or of self-harm among patients with epilepsy or
      MS, (2) identify risk factors for such thoughts, and (3) determine whether any
      risk factors interact with depression to predict such thoughts. METHODS: A
      Cleveland Clinic database provided information on 20,734 visits of 6586
      outpatients with epilepsy or MS. Outcome measures were thoughts of death or self
      harm (Patient Health Questionnaire [PHQ] item-9), and total score >=10 for the 8
      remaining PHQ items (probable major depression). Generalized estimating equations
      accounted for repeat visits in tests of associations of PHQ item-9 responses with
      depression, age, sex, race, household income, disease severity, and quality of
      life. RESULTS: Prevalence of thoughts of death or self-harm averaged 14.4%
      overall (epilepsy, 14.0% and MS, 14.7%). Factors associated with positive PHQ
      item-9 responses in epilepsy were depression and male sex, modified by poor
      quality of life. Factors associated with positive PHQ item-9 in MS were
      depression, male sex, medical comorbidity, and poor quality of life; the effect
      of depression was worse with greater MS severity and being unmarried.
      CONCLUSIONS: Among patients with common neurologic disorders (epilepsy or MS),
      14%-15% reported thoughts of death or self-harm associated with illness severity,
      depression, quality of life, male sex, and being unmarried. Such patients require
      further evaluation of clinical outcomes and effects of treatment.

PMID- 25619674
TI  - Psychosomatic medicine training as a bridge to practice: training and
      professional practice patterns of early career psychosomatic medicine
      specialists.
AB  - BACKGROUND: The number of interested candidates for psychosomatic medicine (PM)
      training programs has not matched the growing need for psychiatrists trained to
      care for complex medically ill patients. The reasons for this lack of growth may
      be found in the experience of new entrants into the subspecialty. OBJECTIVE: To
      investigate this issue, we conducted a survey of early career psychiatrists
      (ECPs) practicing PM to identify the personal and professional characteristics of
      ECP PM specialists and to examine the relevance of PM training to professional
      practice. METHODS: ECPs who attended the 2012 Academy of Psychosomatic Medicine
      annual meeting or who were registered members of the Academy of Psychosomatic
      Medicine completed a survey on training and work experiences. Decisional factors
      associated with pursuit of subspecialty fellowship education and professional
      practice patterns were identified using descriptive statistics and chi-square
      tests. RESULTS: A total of 102 ECPs completed the survey. Of the respondents, 67
      (67%) had completed a PM fellowship. Motivating factors for pursuing fellowship
      training included (1) obtaining additional clinical training, (2) developing a
      special interest in PM training, and (3) improving job candidacy. Overall, 80% of
      ECPs desired inpatient consultation-liaison positions at the time of fellowship
      graduation. Overall, 22% reported difficulty in obtaining employment in PM after
      training. Chi-square tests between subjects who pursued a PM fellowship and those
      who did not proved nonsignificant. CONCLUSIONS: PM fellowship training remains
      relevant and important to ECPs in this sample. The survey results can be used to
      shape institutional and professional supports to better meet early career
      transition needs for PM psychiatrists.

PMID- 25619675
TI  - Interplay of anxiety and depression with quality of life in endstage renal
      disease.
AB  - BACKGROUND: Endstage renal disease (ESRD) is increasingly being recognized as a
      major public health issue globally. Planning of intervention measures is
      preferably hinged on what is known about outcome parameters. OBJECTIVES: This
      study investigated the influence of anxiety with depression and psychosocial- and
      treatment-related correlates on quality of life (QOL) in ESRD. METHODOLOGY:
      Overall, 100 eligible individuals with ESRD were recruited by systematic random
      sampling technique. They were initially interviewed using the
      sociodemographic/clinical profile questionnaire, followed by assessment with the
      Hospital Anxiety and Depression Scale. Subsequently, subjective QOL of
      participants was assessed using the World Health Organization QOL-BREF. RESULTS:
      The mean age of participants was 41.9 +/- 10.9 years, and males (55.0%) were
      preponderant. A total of 29 (29.0%) participants had diagnosable anxiety with
      depression psychopathology based on Hospital Anxiety and Depression Scale scores
      >= 8. Different degrees of impairment across domains of QOL were observed.
      Factors like being employed, married status, younger age, and spending less on
      treatment correlated positively with good QOL across specific domains, whereas
      comorbid anxiety with depression, history of dialysis, monthly income less than
      ?50,000 ($300), and having up to 50 dialysis sessions correlated negatively with
      good outcome in specific domains of QOL (p < 0.05). However, only age,
      anxiety/depression, employment, and history of dialysis were independently
      related to QOL following logistic regression analyses. CONCLUSION: The care of
      ESRD should be matched with need-based mental health services, and psychosocial
      support across important illness trajectories is indicated for best outcome.
      Further research among people with ESRD is also warranted.

PMID- 25619676
TI  - Psychogenic nonepileptic seizure patterns in patients with epilepsy.
AB  - BACKGROUND: Psychogenic nonepileptic seizures (PNESs) clinically resemble
      epileptic seizures (ESs) without concomitant electroencephalograph (EEG) changes.
      Although most studies focus on the differences between ESs and PNESs in different
      groups of patients, few studies have focused on patients with a comorbidity of
      PNESs and ESs. OBJECTIVES: The aim of this study, was to establish the pattern of
      relationships between PNESs and ESs in patients who had both types of events
      during long-term video EEG monitoring, expecting to find that PNESs would be
      longer, more frequent, and more dramatic than ESs. METHODS: This retrospective
      study included only patients who had both ESs and PNESs during long-term video
      EEG monitoring. RESULTS: 12 patients with both types of seizures during long-term
      video EEG monitoring were recruited. Taking into account the hypothesized
      differentiating pattern (number of PNESs >= ESs, duration of PNESs >= ESs, and
      semiology of PNESs >= ESs), in 8 patients, all 3 conditions were fulfilled; in 3,
      2 conditions were fulfilled; and in only 1, none of the conditions were
      fulfilled. CONCLUSION: Although there are semiological similarities between PNESs
      and ESs in the PNES + ES group of patients, there is still a recognizable pattern
      of differences between these 2 states, with characteristics of PNESs resembling
      those of PNESs in patients with PNESs alone-dramatic and prolonged seizures.
      Provoking PNESs during long-term video EEG monitoring can cause diversion from
      the pattern, raising the suspicion of provoking pseudo-PNESs. Although this
      finding needs to be further investigated provocation should be used cautiously.

PMID- 25619677
TI  - Phantom shocks and automated implantable cardioverter defibrillators.

PMID- 25619678
TI  - Depersonalization/derealization disorder after exposure to mefloquine.

PMID- 25619679
TI  - Organic depersonalization as a chronic sequela of mefloquine intoxication.

PMID- 25619680
TI  - Native fold and docking pose discrimination by the same residue-based scoring
      function.
AB  - Structure prediction and quality assessment are crucial steps in modeling native
      protein conformations. Statistical potentials are widely used in related
      algorithms, with different parametrizations typically developed for different
      contexts such as folding protein monomers or docking protein complexes. Here, we
      describe BACH-SixthSense, a single residue-based statistical potential that can
      be successfully employed in both contexts. BACH-SixthSense shares the same
      approach as BACH, a knowledge-based potential originally developed to score
      monomeric protein structures. A term that penalizes steric clashes as well as the
      distinction between polar and apolar sidechain-sidechain contacts are crucial
      novel features of BACH-SixthSense. The performance of BACH-SixthSense in
      discriminating correctly the native structure among a competing set of decoys is
      significantly higher than other state-of-the-art scoring functions, that were
      specifically trained for a single context, for both monomeric proteins (QMEAN,
      Rosetta, RF_CB_SRS_OD, benchmarked on CASP targets) and protein dimers (IRAD,
      Rosetta, PIE*PISA, HADDOCK, FireDock, benchmarked on 14 CAPRI targets). The
      performance of BACH-SixthSense in recognizing near-native docking poses within
      CAPRI decoy sets is good as well.

PMID- 25619681
TI  - Hsp90 is involved in the regulation of cytosolic precursor protein abundance in
      tomato.
AB  - Cytosolic chaperones are involved in the regulation of cellular protein
      homeostasis in general. Members of the families of heat stress proteins 70
      (Hsp70) and 90 (Hsp90) assist the transport of preproteins to organelles such as
      chloroplasts or mitochondria. In addition, Hsp70 was described to be involved in
      the degradation of chloroplast preproteins that accumulate in the cytosol.
      Because a similar function has not been established for Hsp90, we analyzed the
      influences of Hsp90 and Hsp70 on the protein abundance in the cellular context
      using an in vivo system based on mesophyll protoplasts. We observed a
      differential behavior of preproteins with respect to the cytosolic chaperone
      dependent regulation. Some preproteins such as pOE33 show a high dependence on
      Hsp90, whereas the abundance of preproteins such as pSSU is more strongly
      dependent on Hsp70. The E3 ligase, C-terminus of Hsp70-interacting protein
      (Chip), appears to have a more general role in the control of cytosolic protein
      abundance. We discuss why the different reaction modes are comparable with the
      cytosolic unfolded protein response. 

PMID- 25619682
TI  - Injection scheme for intravitreal bevacizumab therapy for macular oedema due to
      central retinal vein occlusion: results of a multicenter study.

PMID- 25619683
TI  - Dietary protein and amino acids intake and its relationship with blood pressure
      in adolescents: the HELENA STUDY.
AB  - OBJECTIVE: To analyze the association between dietary protein and amino acids
      intake and systolic (SBP) and diastolic (DBP) blood pressure in European
      adolescents. METHODS: Participants were from the cross-sectional study performed
      in Europe, Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA study;
      n = 1605; 12.5-17.5 years; 833 girls) selected by complex sampling. The
      associations between dietary protein and amino acids intake and SBP/DBP were
      examined by multilevel linear regression models (context variable by school); the
      analysis being stratified by sex. Cities, seasonality, age, socioeconomic level,
      parental education level, body mass index, waist circumference, Tanner stage and
      physical activity were used as covariates. RESULTS: In boys, we found an inverse
      association between protein (animal and vegetable) intake and DBP; and a positive
      association between histidine and SBP. In girls, we observed a positive
      association among tryptophan, histidine with SBP and methionine with DBP. On the
      other hand, we observed an inverse association between tyrosine and both SBP and
      DBP levels in girls. CONCLUSIONS: The association between amino acids and BP
      levels is controversial and depends on the type of amino acids, and protein
      intake can help control the DBP in boys.

PMID- 25619684
TI  - A longitudinal study on intrinsic connectivity of hippocampus associated with
      positive symptom in first-episode schizophrenia.
AB  - Hippocampal pathology has been considered to underlie clinical, functional and
      cognitive impairments in schizophrenia. While longitudinal magnetic resonance
      imaging (MRI) studies have demonstrated progressive gray matter reduction of the
      hippocampus during the early phases of schizophrenia (SCZ), very little is known
      about whether functional connectivity (FC) between the hippocampus and other
      brain regions also exhibit progressive changes. In this study, resting state
      functional MRI (fMRI) was used to examine changes in hippocampal connectivity at
      baseline and follow-up scans comparing 68 patients with first episode SCZ and 62
      matched controls. At baseline and follow-up, in the bilateral hippocampal
      network, SCZ mainly showed decreased FC with bilateral cerebellum posterior lobe,
      frontal gyrus temporal gyrus, precuneus, and cingulate cortex compared to
      controls. Furthermore, in the bilateral hippocampus, there was a significant
      interaction effect of group and time for FC with cerebellum posterior lobe,
      temporal gyrus, frontal gyrus, and posterior cingulate cortex. Interestingly,
      longitudinal changes of bilateral hippocampal connectivity with right middle
      frontal gyrus negatively correlated with positive symptom scores in SCZ. These
      results provide novel evidence for the progressive changes of FC between
      hippocampus and other brain regions in SCZ. It further suggests that longitudinal
      changes of bilateral hippocampal connectivity with right middle frontal gyrus can
      contribute to the formation and emergence of positive symptom of SCZ.

PMID- 25619685
TI  - Cholinergic modulation of stimulus-driven attentional capture.
AB  - Distraction is one of the main problems encountered by people with degenerative
      diseases that are associated with reduced cortical cholinergic innervations. We
      examined the effects of donepezil, a cholinesterase inhibitor, on stimulus-driven
      attentional capture. Reflexive attention shifts to a distractor are usually
      elicited by abrupt peripheral changes. This bottom-up shift of attention to a
      salient item is thought to be the result of relatively inflexible hardwired
      mechanisms. Thirty young male participants were randomly allocated to one of two
      groups: placebo first/donepezil second session or the opposite. They were asked
      to locate a target appearing above and below fixation whilst a peripheral
      distractor moved abruptly (motion-jitter attentional capture condition) or not
      (baseline condition). A classical attentional capture effect was observed under
      placebo: moving distractors interfered with the task in slowing down response
      times as compared to the baseline condition with fixed distractors. Increased
      interference from moving distractors was found under donepezil. We suggest that
      attentional capture in our paradigm likely involved low level mechanisms such as
      automatic reflexive orienting. Peripheral motion-jitter elicited a rapid
      reflexive orienting response initiated by a cholinergic signal from the brainstem
      pedunculo-pontine nucleus that activates nicotinic receptors in the superior
      colliculus.

PMID- 25619686
TI  - Three-Arm Randomized Phase III Trial: Quality Aloe and Placebo Cream Versus
      Powder as Skin Treatment During Breast Cancer Radiation Therapy.
AB  - BACKGROUND: The efficacy of aloe extract in reducing radiation-induced skin
      injury is controversial. The purpose of the present 3-arm randomized trial was to
      test the efficacy of quality-tested aloe extract in reducing the severity of
      radiation-induced skin injury and, secondarily, to examine the effect of a moist
      cream versus a dry powder skin care regimen. MATERIALS AND METHODS: A total of
      248 patients with breast cancer were randomized to powder, aloe cream, or placebo
      cream. Acute skin toxicity was scored weekly and after treatment at weeks 1, 2,
      and 4 using a modified 10-point Catterall scale. The patients scored their
      symptom severity using a 6-point Likert scale and kept an acute phase diary.
      RESULTS: The aloe formulation did not reduce acute skin toxicity or symptom
      severity. Patients with a greater body mass index were more likely to develop
      acute skin toxicity. A similar pattern of increased skin reaction toxicity
      occurred with both study creams compared with the dry powder regimen. CONCLUSION:
      No evidence was found to support prophylactic application of quality aloe extract
      or cream to improve the symptoms or reduce the skin reaction severity. Our
      results support a dry skin care regimen of powder during radiation therapy.

PMID- 25619687
TI  - Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2+ leak
      in cardiomyocytes: Role of adenine nucleotide translocase.
AB  - Long chain fatty acids bind to carnitine and form long chain acyl carnitine
      (LCAC), to enter into the mitochondria. They are oxidized in the mitochondrial
      matrix. LCAC accumulates rapidly under metabolic disorders, such as acute cardiac
      ischemia, chronic heart failure or diabetic cardiomyopathy. LCAC accumulation is
      associated with severe cardiac arrhythmia including ventricular tachycardia or
      fibrillation. We thus hypothesized that palmitoyl-carnitine (PC), alters
      mitochondrial function leading to Ca(2+) dependent-arrhythmia. In isolated
      cardiac mitochondria from C57Bl/6 mice, application of 10MUM PC decreased adenine
      nucleotide translocase (ANT) activity without affecting mitochondrial
      permeability transition pore (mPTP) opening. Mitochondrial reactive oxygen
      species (ROS) production, measured with MitoSOX Red dye in isolated ventricular
      cardiomyocytes, increased significantly under PC application. Inhibition of ANT
      by bongkrekic acid (20 MUM) prevented PC-induced mitochondrial ROS production. In
      addition, PC increased type 2 ryanodine receptor (RyR2) oxidation, S
      nitrosylation and dissociation of FKBP12.6 from RyR2, and therefore increased
      sarcoplasmic reticulum (SR) Ca(2+) leak. ANT inhibition or anti-oxidant strategy
      (N-acetylcysteine) prevented SR Ca(2+) leak, FKBP12.6 depletion and RyR2
      oxidation/S-nitrosylation induced by PC. Finally, both bongkrekic acid and NAC
      significantly reduced spontaneous Ca(2+) wave occurrences under PC. Altogether,
      these results suggest that an elevation of PC disturbs ANT activity and alters
      Ca(2+) handling in a ROS-dependent pathway, demonstrating a new pathway whereby
      altered FA metabolism may contribute to the development of ventricular arrhythmia
      in pathophysiological conditions.

PMID- 25619688
TI  - Disease-specific alterations in the enteric virome in inflammatory bowel disease.
AB  - Decreases in the diversity of enteric bacterial populations are observed in
      patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known
      about the virome in these diseases. We show that the enteric virome is abnormal
      in CD and UC patients. In-depth analysis of preparations enriched for free
      virions in the intestine revealed that CD and UC were associated with a
      significant expansion of Caudovirales bacteriophages. The viromes of CD and UC
      patients were disease and cohort specific. Importantly, it did not appear that
      expansion and diversification of the enteric virome was secondary to changes in
      bacterial populations. These data support a model in which changes in the virome
      may contribute to intestinal inflammation and bacterial dysbiosis. We conclude
      that the virome is a candidate for contributing to, or being a biomarker for,
      human inflammatory bowel disease and speculate that the enteric virome may play a
      role in other diseases.

PMID- 25619689
TI  - Reduced expression of MYC increases longevity and enhances healthspan.
AB  - MYC is a highly pleiotropic transcription factor whose deregulation promotes
      cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit
      increased lifespan. They show resistance to several age-associated pathologies,
      including osteoporosis, cardiac fibrosis, and immunosenescence. They also appear
      to be more active, with a higher metabolic rate and healthier lipid metabolism.
      Transcriptomic analysis reveals a gene expression signature enriched for
      metabolic and immune processes. The ancestral role of MYC as a regulator of
      ribosome biogenesis is reflected in reduced protein translation, which is
      inversely correlated with longevity. We also observe changes in nutrient and
      energy sensing pathways, including reduced serum IGF-1, increased AMPK activity,
      and decreased AKT, TOR, and S6K activities. In contrast to observations in other
      longevity models, Myc(+/-) mice do not show improvements in stress management
      pathways. Our findings indicate that MYC activity has a significant impact on
      longevity and multiple aspects of mammalian healthspan.

PMID- 25619690
TI  - Cancer-associated protein kinase C mutations reveal kinase's role as tumor
      suppressor.
AB  - Protein kinase C (PKC) isozymes have remained elusive cancer targets despite the
      unambiguous tumor promoting function of their potent ligands, phorbol esters, and
      the prevalence of their mutations. We analyzed 8% of PKC mutations identified in
      human cancers and found that, surprisingly, most were loss of function and none
      were activating. Loss-of-function mutations occurred in all PKC subgroups and
      impeded second-messenger binding, phosphorylation, or catalysis. Correction of a
      loss-of-function PKCbeta mutation by CRISPR-mediated genome editing in a patient
      derived colon cancer cell line suppressed anchorage-independent growth and
      reduced tumor growth in a xenograft model. Hemizygous deletion promoted anchorage
      independent growth, revealing that PKCbeta is haploinsufficient for tumor
      suppression. Several mutations were dominant negative, suppressing global PKC
      signaling output, and bioinformatic analysis suggested that PKC mutations
      cooperate with co-occurring mutations in cancer drivers. These data establish
      that PKC isozymes generally function as tumor suppressors, indicating that
      therapies should focus on restoring, not inhibiting, PKC activity.

PMID- 25619692
TI  - Surgical treatment of displaced middle-third clavicular fractures: a prospective,
      randomized trial in a working compensation population.
AB  - BACKGROUND: Surgical treatment with open reduction and internal fixation (ORIF)
      of displaced middle-third clavicular fractures resulted in shorter complete
      return to work periods with earlier consolidation documented on computed
      tomography (CT) scans in this prospective, randomized controlled trial. METHODS:
      The study randomized 76 consecutive patients with displaced fractures (2B1-2B2
      according to Robinson) to conservative (C, n = 42) and surgical (S, n = 34)
      treatment with plates and screws. Bone union was documented with CT scans at 6
      and 12 weeks. RESULTS: Risk factors known to increase the risk of nonunion were
      similar between groups. Time until discharge for complete return to work was 3.7
      +/- 1.1 months for C and 2.9 +/- 0.8 months for S (P = .003). On the CT scan at 6
      weeks, 24.1% of the patients presented advanced bone union in S vs 5.3% in C (P =
      .05). At 12 weeks, 81% of the patients presented advanced bone union in S vs
      16.7% in C (P = .005). At final follow-up, 4 nonunions were present in the C
      group that required surgery; in the S group, 4 patients underwent revision
      surgery for plate removal. At 6 and 12 months of follow-up, Constant scores were
      higher for the S group. CONCLUSIONS: Surgical treatment with ORIF of displaced
      middle-third clavicular fractures achieved good and excellent functional results,
      shorter time to complete return to work, earlier bone union, and fewer cases of
      nonunions in a working population under injury compensation.

PMID- 25619694
TI  - Theoretical studies on POM-based organic-inorganic hybrids containing double D-A1
      pi-A2 chains for high-performance p-type, dye-sensitized solar cells (DSSCs).
AB  - Polyoxometalate (POM)-based organic-inorganic hybrid systems are designed as p
      type dyes containing double D-A1-pi-A2 chains. The A1 spacers are thiophene,
      1,2,3-triazole, 1,3,4-oxadlazole, thienothiadiazole units or their combinations
      and the A2 spacer is hexamolybdate. The electronic structures, absorption
      spectra, and electronic transition characteristics of systems were systematically
      studied on the basis of density functional theory (DFT) and time-dependent DFT
      (TDDFT). The highest occupied molecular orbital (HOMO) levels of systems were
      below the valence bond (VB) of NiO and the lowest unoccupied molecular orbital
      (LUMO) levels of studied systems were higher than the I2/I3(-) redox level, which
      benefit hole injection and dye regeneration. The HOMOs of systems were
      predominantly delocalized over the organic groups and Mo[triple bond, length as m
      dash]N, which are more helpful to hole injection than systems . Introduction of
      thienothiadiazole units is an effective way to improve the light absorption
      ability of dyes, and inserting thiophene and 1,2,3-triazole as A1 spacers can
      increase the efficiency of dye in dye-sensitized solar cells (DSSC). 

PMID- 25619691
TI  - Ligand-dependent enhancer activation regulated by topoisomerase-I activity.
AB  - The discovery that enhancers are regulated transcription units, encoding eRNAs,
      has raised new questions about the mechanisms of their activation. Here, we
      report an unexpected molecular mechanism that underlies ligand-dependent enhancer
      activation, based on DNA nicking to relieve torsional stress from eRNA synthesis.
      Using dihydrotestosterone (DHT)-induced binding of androgen receptor (AR) to
      prostate cancer cell enhancers as a model, we show rapid recruitment, within
      minutes, of DNA topoisomerase I (TOP1) to a large cohort of AR-regulated
      enhancers. Furthermore, we show that the DNA nicking activity of TOP1 is a
      prerequisite for robust eRNA synthesis and enhancer activation and is kinetically
      accompanied by the recruitment of ATR and the MRN complex, followed by additional
      components of DNA damage repair machinery to the AR-regulated enhancers.
      Together, our studies reveal a linkage between eRNA synthesis and ligand
      dependent TOP1-mediated nicking-a strategy exerting quantitative effects on eRNA
      expression in regulating AR-bound enhancer-dependent transcriptional programs. 

PMID- 25619693
TI  - HOS1 regulates Argonaute1 by promoting transcription of the microRNA gene MIR168b
      in Arabidopsis.
AB  - Proper accumulation and function of miRNAs is essential for plant growth and
      development. While core components of the miRNA biogenesis pathway and miRNA
      induced silencing complex have been well characterized, cellular regulators of
      miRNAs remain to be fully explored. Here we report that High Expression Of
      Osmotically Responsive Genes1 (HOS1) is a regulator of an important miRNA,
      mi168a/b, that targets the Argonaute1 (AGO1) gene in Arabidopsis. HOS1 functions
      as an ubiquitin E3 ligase to regulate plant cold-stress responses, associates
      with the nuclear pores to regulate mRNA export, and regulates the circadian clock
      and flowering time by binding to chromatin of the flowering regulator gene
      Flowering Locus C (FLC). In a genetic screen for enhancers of sic-1, we isolated
      a loss-of-function Arabidopsis mutant of HOS1 that is defective in miRNA
      biogenesis. Like other hos1 mutant alleles, the hos1-7 mutant flowered early and
      was smaller in stature than the wild-type. Dysfunction in HOS1 reduced the
      abundance of miR168a/b but not of other miRNAs. In hos1 mutants, pri-MIR168b and
      pre-MIR168b levels were decreased, and RNA polymerase II occupancy was reduced at
      the promoter of MIR168b but not that of MIR168a. Chromatin immunoprecipitation
      assays revealed that HOS1 protein is enriched at the chromatin of the MIR168b
      promoter. The reduced miR168a/b level in hos1 mutants results in an increase in
      the mRNA and protein levels of its target gene, AGO1. Our results reveal that
      HOS1 regulates miR168a/b and AGO1 levels in Arabidopsis by maintaining proper
      transcription of MIR168b.

PMID- 25619695
TI  - Altitudinal variation of soil organic carbon stocks in temperate forests of
      Kashmir Himalayas, India.
AB  - Soil organic carbon stocks were measured at three depths (0-10, 10-20, and 20-30
      cm) in seven altitudes dominated by different forest types viz. Populus
      deltoides, 1550-1800 m; Juglans regia, 1800-2000 m; Cedrus deodara, 2050-2300 m;
      Pinus wallichiana, 2000-2300 m; mixed type, 2200-2400 m; Abies pindrow, 2300-2800
      m; and Betula utilis, 2800-3200 m in temperate mountains of Kashmir Himalayas.
      The mean range of soil organic carbon (SOC) stocks varied from 39.07 to 91.39 Mg
      C ha(-1) in J. regia and B. utilis forests at 0-30 cm depth, respectively. Among
      the forest types, the lowest mean range of SOC at three depths (0-10, 10-20, and
      20-30 cm) was observed in J. regia (18.55, 11.31, and 8.91 Mg C ha(-1),
      respectively) forest type, and the highest was observed in B. utilis (54.10,
      21.68, and 15.60 Mg C ha(-1), respectively) forest type. SOC stocks showed
      significantly (R (2) = 0.67, P = 0.001) an increasing trend with increase in
      altitude. On average, the percentages of SOC at 0-10-, 10-20-, and 20-30-cm
      depths were 53.2, 26.5, and 20.3 %, respectively. Bulk density increased
      significantly with increase in soil depth and decreased with increase in
      altitude. Our results suggest that SOC stocks in temperate forests of Kashmir
      Himalaya vary greatly with forest type and altitude. The present study reveals
      that SOC stocks increased with increase in altitude at high mountainous regions.
      Climate change in these high mountainous regions will alter the carbon
      sequestration potential, which would affect the global carbon cycle.

PMID- 25619696
TI  - Spatial variability of available soil microelements in an ecological functional
      zone of Beijing.
AB  - Understanding the spatial variability of soil microelements and its influencing
      factors is of importance for a number of applications such as scientifically
      formulated fertilizer and environmental protection. This study used descriptive
      statistics and geostatistics to investigate the spatial variability of available
      soil Fe, Mn, Cu, and Zn contents in agricultural topsoil (0-20 cm) in an
      ecological functional zone located at Yanqing County, Beijing, China. Kriging
      method was applied to map the spatial patterns of available soil Fe, Mn, Cu, and
      Zn contents. Results showed that the available soil Cu had a widest spatial
      correlation distance (e.g., 9.6 km), which for available soil Fe, Mn, and Zn were
      only 1.29, 2.58, and 0.99 km, respectively. The values of C 0/sill for available
      soil Fe and Zn were 0.12 and 0.11, respectively, demonstrating that the spatial
      heterogeneity was mainly due to structural factors. The available soil Mn and Cu
      had the larger values of C 0/sill (i.e., 0.50 and 0.44 for Mn and Cu,
      respectively), which showed a medium spatial correlation. Mapping of the spatial
      patterns of the four microelements showed that the decrease trend of available
      soil Fe and Mn were from northeast to southwest across the study area. The
      highest amount of available soil Cu was distributed in the middle of the study
      area surrounding urban region which presented as a "single island". The highest
      amount of available soil Zn was mainly distributed in the north and south of the
      study area. One-way analysis of variance for the influencing factors showed that
      the lithology of parental materials, soil organic matter, and pH were important
      factors affecting spatial variability of the available microelements. The
      topography only had a significant influence on the spatial variability of
      available soil Fe and Mn contents, parental materials, and the land use types had
      little influence on the spatial variability.

PMID- 25619697
TI  - Anthropogenic impact on water chemistry and benthic macroinvertebrate associated
      changes in a southern Nigeria stream.
AB  - The Ogba River in southern Nigeria is an important water resource for its
      riparian communities. This study evaluates impact of anthropogenic influences on
      the Ogba River using water chemistry and macroinvertebrate data sets obtained
      over a period of 6 months between January and June 2012. Four stations, stations
      1-4, characterised by various human activities were chosen along the river.
      Organic wastes from domestic and industrial sources were the major point sources
      of pollutants. Station 2 where the municipal wastewater drains into the river had
      elevated values of flow velocity, BOD5, sulphate, phosphate, nitrate and sodium.
      Based on the canonical correspondence analysis (CCA), 5-day biochemical oxygen
      demand (BOD5), sulphate, nitrate and phosphate were the main factors that help to
      shape the macroinvertebrate assemblage structure of the Ogba River.
      Macroinvertebrates clustered strongly by stations than by seasons indicating that
      water quality differences between the stations were responsible for the observed
      differences in the biotic assemblage. The preponderance of naidid oligochaetes,
      baetid nymphs and certain tolerant dipteran taxa including chironomids and
      ceratopogonids at all four stations was an indication that the entire water body
      was stressed. The odonates were the single most abundant taxa; their dominance
      could be attributed to the vegetative nature of the stream, favouring odonate
      colonisation. Overall, the responses of macroinvertebrates to stress were
      reflected by the different assemblage structures recorded at the four study
      stations. Substrate and microhabitat obliteration and poor water quality appeared
      to be the factors responsible for the observed assemblage structure in the Ogba
      River.

PMID- 25619698
TI  - Identifying best methods for routine ELISA detection of microcystin in seafood.
AB  - Ingestion of water contaminated with the cyanotoxin, microcystin (MC), can pose
      serious health risks to humans. MC is also known to accumulate in seafood;
      however, this exposure pathway is much less understood. A fundamental element of
      this uncertainty is related to analytical difficulties. Commercially available
      enzyme-linked immunosorbent assays (ELISAs) offer one of the best options for
      routine MC detection, but methods of detecting MC in tissue are far from
      standardized. We spiked freshwater finfish and marine mussel tissues with MC,
      then compared recovery rates using four different preparation protocols and two
      ELISA types (polyclonal anti-MC-ADDA/direct monoclonal (DM)). Preparation
      protocol, type of ELISA, and seafood tissue variety significantly affected MC
      detection. This is the first known study to use DM ELISA for tissue analyses, and
      our findings demonstrate that DM ELISA combined with a short solvent extraction
      results in fewer false positives than other commonly used methods. This method
      can be used for rapid and reliable MC detection in seafood. 

PMID- 25619699
TI  - You...can be a millionaire.

PMID- 25619700
TI  - Can the deadman be killed?

PMID- 25619701
TI  - Author's reply: The "deadman" concept in practice: should we believe a
      mathematical theory or accept the experimental evidence?

PMID- 25619702
TI  - Authors' reply.

PMID- 25619703
TI  - Health care cost consciousness: testing triceps strength instead of routinely
      ordering imaging procedures.

PMID- 25619704
TI  - In memorium: Donald Raymond Buhler (1925-2014).

PMID- 25619705
TI  - What do changes in concentrations of serum surfactant proteins A and D in OSA
      mean?
AB  - PURPOSE: Previous studies have shown that surfactant proteins are affected by
      oxygen concentration and mechanic stretches, although the alteration of serum
      surfactant proteins in individuals with obstructive sleep apnea (OSA) is still
      unclear. Therefore, the aim of this study is to examine whether serum
      concentrations of surfactant proteins A and D are altered and related to hypopnea
      index (HI) in OSA. METHODS: This is a cross-sectional study. Consecutive 140
      males, suspicious of OSA, were studied. OSA was determined by PSG and
      polysomnographic data examined. Subjects with HI >= 10.1/h were classified as
      higher HI group and those with HI < 10.1/h as lower HI group. Hs-CRP, HbA1C, and
      FBG were determined by standard methods and Krebs von den Lungen-6 (KL-6),
      surfactant protein-A (SP-A), and surfactant protein-D (SP-D) by ELISA. RESULTS:
      OSA was diagnosed in 110 patients (78.5%). Mild, moderate, and severe OSA
      constitutes 26.4, 27.8, and 24.3%, respectively. Mean age was 44.6 +/- 7.65
      years. Subjects with higher HI had lower SP-A (139.54. +/- 32.94 vs 158.2 +/-
      38.9 ng/L, p = 0.005) and SP-D (16.54 +/- 3.67 vs 18.10 +/- 3.48 ng/L, p = 0.014)
      compared to those with lower HI. Nocturnal HI was strongly correlated with serum
      levels of SP-A (r = 0.343, p = 0.012) and SP-D (r = 0.504, p < 0.001) and are
      inversely associated with circulating SP-A and SP-D levels, even after adjusting
      for age and body mass index in nonsmoking subjects. CONCLUSIONS: Circulating SP-A
      and SP-D levels are decreased in some individuals with higher HI in OSA, possibly
      reflecting severity of hypoxia in OSA.

PMID- 25619706
TI  - Risk of insomnia with non-vitamin K oral anticoagulants: systematic review and
      meta-analysis.
AB  - PURPOSE: Insomnia is an important adverse event of mechanical thromboprophylaxis.
      This sleep disorder has been reported as one of the commonest adverse events of
      the new oral anti-Xa anticoagulant darexaban, with similar rates to mechanical
      thromboprophylaxis in a randomized controlled trial (RCT). However, the perceived
      effect could have been biased because it was an open-label RCT. Therefore, we
      aimed to review the incidence of insomnia with non-vitamin K antagonist oral
      anticoagulants (NOACs). METHODS: We performed a systematic review and meta
      analysis of Phase III RCTs. Electronic databases MEDLINE and CENTRAL (inception
      to September 2013) were searched as well as review articles and references of
      included studies. We included phase III RCTs which compared NOACs with any other
      control group. Data were analyzed and pooled to estimate risk ratio (RR) with 95%
      confidence intervals (95%CI) for insomnia using inverse variance method.
      Statistical heterogeneity was evaluated with I(2) test. RESULTS: We included
      seven studies (two apixaban RCTs, two dabigatran RCTs, one darexaban RCTs, and
      two rivaroxaban RCTs), enrolling a total of 23,023 patients. Overall, NOACs were
      not associated to an increased risk of insomnia: RR 0.94 (95%CI 0.83-1.08; I(2) =
      0%). In blinded studies (six studies), NOACs also did not show increased risk of
      insomnia (RR 0.94, 95%CI 0.83-1.08; I(2) = 0%). Results were similar irrespective
      of the comparators. CONCLUSIONS: NOACs (apixaban, dabigatran, darexaban,
      rivaroxaban) did not show increased risk of insomnia. Results according to study
      design (blinded vs. open-label trials) overlap the main analysis.

PMID- 25619707
TI  - Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a
      study in 1744 patients.
AB  - OBJECTIVE: We analyze a large population of patients to determine whether gamma
      glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome
      (OSA) and whether these levels are related to clinical characteristics or
      polygraphic indexes. METHODS: A cross-sectional study in a population of 1744
      patients referred for OSA suspicion was conducted. The following variables were
      determined: glucose, cholesterol, triglycerides, aspartate aminotransferase
      (GOT), alanine aminotransferase (GPT), GGT, body mass index, waist-hip ratio
      (WHR), and overnight sleep study. RESULTS: The 483 patients with GGT >=40 IU/l
      were younger and more obese, and had a pattern of more centrally distributed fat
      than the 1261 with GGT <40 IU/l. Patients with high levels of GGT also consumed
      more alcohol, had a poorer biochemical profile, and had more respiratory and
      oximetric alterations during sleep. GGT levels were significantly correlated with
      AHI, DI, and CT90. In the binary regression test, WHR, glucose, cholesterol,
      triglycerides, and grams of alcohol consumed per day predicted GGT levels >=40
      IU/l, while none of the polygraphic variables had predictive value. CONCLUSIONS:
      High GGT levels were associated with the severity of OSA. However, this
      relationship seems to be due to the coexistence of other associated factors,
      mainly central obesity, rather than to the respiratory disorders found in this
      disease.

PMID- 25619708
TI  - Chiral conductive polymers as spin filters.

PMID- 25619709
TI  - Severe measles pneumonia in adults with respiratory failure: role of ribavirin
      and high-dose vitamin A.
AB  - Although measles is usually considered a benign viral disease of childhood,
      adults may be affected at any age and may experience severe respiratory or
      neurologic consequences. We present three adult cases (one of whom was pregnant)
      admitted to our University Hospital who were diagnosed to have measles and who
      had uncommon clinical features such as hepatitis and hyponatremia. All patients
      were markedly hypoxic; one required mechanical ventilation. Two patients received
      therapy with intravenous ribavirin and all patients received high-dose vitamin A
      for 3 days. Therapy with intravenous ribavirin and vitamin A were well tolerated
      by our patients except one patient who developed acute renal failure and were
      associated with reversal of respiratory compromise. Life-threatening measles
      pneumonitis in adults may be more common than previously appreciated, regardless
      of the patient's immune status, and ribavirin and high-dose vitamin A might be a
      treatment option. 

PMID- 25619712
TI  - Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine
      tumors.
AB  - Over the past few years, knowledge regarding the molecular pathology of sporadic
      pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a
      number of targeted agents have been tested in clinical trials in this tumor type.
      For some of these agents there is a strong biological rationale. Among them, the
      mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent
      Sunitinib have both been approved for the treatment of PNETs. However, there is
      lack of knowledge regarding biomarkers able to predict their efficacy, and
      mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib,
      inhibitors of Src, Hedgehog or of PI3K might all be useful in association or
      sequence with approved agents. On the other hand, the clinical significance, and
      potential for treatment of the most common mutations occurring in sporadic PNETs,
      in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper
      reviews the main molecular changes occurring in PNETs and how they might be
      linked with treatment options. 

PMID- 25619713
TI  - Simultaneous determination of tebuconazole, trifloxystrobin, and its metabolite
      trifloxystrobin acid residues in gherkin under field conditions.
AB  - A rapid, simple, and selective analytical method for the simultaneous
      determination of tebuconazole, trifloxystrobin, and its metabolite
      trifloxystrobin acid residues in gherkin and soil was developed and validated by
      gas chromatography coupled with mass spectrometry. The samples were extracted
      with acetonitrile and cleaned up by dispersive solid-phase extraction with
      primary secondary amine sorbent. The limit of quantification of the method was
      0.05 mg/kg for all three compounds. The method was validated using blank samples
      spiked at three levels and recoveries ranged from 83.5 to 103.8% with a relative
      standard deviation of 1.2 to 4.8%. The developed method was validated and applied
      for the analysis of a degradation study sample. The residues of trifloxystrobin
      and tebuconazole were found to dissipate following first-order kinetics with half
      life ranging between 3.31-3.38 and 3.0-3.04 days, respectively, for two different
      dosages. Pesticide residues were below the European Union maximum residue level
      after seven days for trifloxystrobin (0.2 mg/kg) and ten days for tebuconazole
      (0.05 mg/kg), which suggested the use of this fungicide mixture to be safe to
      humans. These results can be utilized in formulating the spray schedule and
      safety evaluation on trifloxystrobin and tebuconazole in gherkin crop.

PMID- 25619715
TI  - New insights into antimetastatic and antiangiogenic effects of cannabinoids.
AB  - Cannabinoids exert antitumorigenic effects via multiple mechanisms. Of these,
      antimetastatic and antiangiogenic actions have attracted considerable interest in
      the past years. Regarding the underlying antimetastatic mechanism, several
      studies revealed cannabinoids to alter the gene expression of cancer cells toward
      a less-aggressive phenotype and to modulate their secretomic profile.
      Cannabinoids likewise modulate the release of factors from tumor cells that
      subsequently suppress the chemoattraction of vessel cells thereby conferring
      antiangiogenesis. Among the diverse mediators of cannabinoids' antitumorigenic
      action, the tissue inhibitor of matrix metalloproteinases-1, which is released
      from cancer cells upon cannabinoid treatment, has been implicated as a pivotal
      factor conferring both anti-invasive properties of cancer cells as well as
      antiangiogenic capacities of endothelial cells. In addition, cannabinoids have
      been shown to inhibit angiogenic capacities of endothelial cells directly via
      suppressing their proliferation, tube formation, and migration. This chapter
      reviews the cell- and substance-specific antitumorigenic mechanisms of
      cannabinoids with particular consideration of their antimetastatic/anti-invasive
      and antiangiogenic actions. In addition, beneficial interactions of cannabinoids
      with currently used chemotherapeutics as well as the influence of cannabinoids on
      tumor-immune surveillance are addressed. Collectively, the currently available
      data suggest cannabinoids as a potential tool in modern cancer pharmacotherapy.

PMID- 25619716
TI  - Insight into the role of Wnt5a-induced signaling in normal and cancer cells.
AB  - Wnt5a is involved in the activation of noncanonical Wnt signaling, including
      planar cell polarity (PCP) and Wnt-Ca(2+) pathways. The Ror-family of receptor
      tyrosine kinases is composed of Ror1 and Ror2 in mammals. Ror2 acts as a receptor
      or coreceptor for Wnt5a and regulates Wnt5a-induced activation of PCP pathway,
      and Wnt5a-Ror2 axis indeed plays critical roles in the developmental
      morphogenesis by regulating cell polarity and migration. Furthermore, Wnt5a-Ror2
      axis is constitutively activated in cancer cells and confers highly motile and
      invasive properties on cancer cells through the expression of matrix
      metalloproteinase genes and enhanced formation of invadopodia. Meanwhile, Wnt5a
      also exhibits a tumor-suppressive function in certain cancers, including breast
      and colorectal carcinomas. Thus, it is of great importance to understand the
      respective molecular mechanisms governing Wnt5a-mediated tumor-progressive and
      tumor-suppressive functions, in order to develop novel and proper diagnostic and
      therapeutic strategies targeting Wnt5a signaling for human cancers. 

PMID- 25619717
TI  - New insight into cancer aneuploidy in zebrafish.
AB  - Aneuploidy is one of the most common genetic alterations in cancer cell genomes.
      It greatly contributes to the heterogeneity of cancer cell genomes, and its roles
      in tumorigenesis are attracting more and more attentions. Zebrafish is emerging
      as a new genetic model for many human diseases including cancer. The zebrafish
      cancer model has shown an equivalent degree of aneuploidy as found in
      corresponding human cancers, thus it provides a great tool for us to study cancer
      aneuploidy and, in general, cancer biology. Here, we discuss some new advances of
      aneuploidy and the potential usages of this cancer model system. 

PMID- 25619714
TI  - Epidermal growth factor signaling in transformed cells.
AB  - Members of the epidermal growth factor receptor (EGFR/ErbB) family play a
      critical role in normal cell growth and development. However, many ErbB family
      members, especially EGFR, are aberrantly expressed or deregulated in tumors and
      are thought to play crucial roles in cancer development and metastatic
      progression. In this chapter, we provide an overview of key mechanisms
      contributing to aberrant EGFR/ErbB signaling in transformed cells, which results
      in many phenotypic changes associated with the earliest stages of tumor
      formation, including several hallmarks of epithelial-mesenchymal transition
      (EMT). These changes often occur through interaction with other major signaling
      pathways important to tumor progression, causing a multitude of transcriptional
      changes that ultimately impact cell morphology, proliferation, and adhesion, all
      of which are crucial for tumor progression. The resulting mesh of signaling
      networks will need to be taken into account as new regimens are designed for
      targeting EGFR for therapeutic intervention. As new insights are gained into the
      molecular mechanisms of cross talk between EGFR signaling and other signaling
      pathways, including their roles in therapeutic resistance to anti-EGFR therapies,
      a continual reassessment of clinical therapeutic regimes and strategies will be
      required. Understanding the consequences and complexity of EGF signaling and how
      it relates to tumor progression is critical for the development of clinical
      compounds and establishing clinical protocols for the treatment of cancer. 

PMID- 25619718
TI  - The amazing ubiquitin-proteasome system: structural components and implication in
      aging.
AB  - Proteome quality control (PQC) is critical for the maintenance of cellular
      functionality and it is assured by the curating activity of the proteostasis
      network (PN). PN is constituted of several complex protein machines that under
      conditions of proteome instability aim to, firstly identify, and then, either
      rescue or degrade nonnative polypeptides. Central to the PN functionality is the
      ubiquitin-proteasome system (UPS) which is composed from the ubiquitin
      conjugating enzymes and the proteasome; the latter is a sophisticated multi
      subunit molecular machine that functions in a bimodal way as it degrades both
      short-lived ubiquitinated normal proteins and nonfunctional polypeptides. UPS is
      also involved in PQC of the nucleus, the endoplasmic reticulum and the
      mitochondria and it also interacts with the other main cellular degradation axis,
      namely the autophagy-lysosome system. UPS functionality is optimum in the young
      organism but it is gradually compromised during aging resulting in increasing
      proteotoxic stress; these effects correlate not only with aging but also with
      most age-related diseases. Herein, we present a synopsis of the UPS components
      and of their functional alterations during cellular senescence or in vivo aging.
      We propose that mild UPS activation in the young organism will, likely, promote
      antiaging effects and/or suppress age-related diseases. 

PMID- 25619720
TI  - Multiple myeloma as a model for the role of bone marrow niches in the control of
      angiogenesis.
AB  - Bone marrow (BM) contains hematopoietic stem cells (HSCs) and nonhematopoietic
      cells. HSCs give rise to all types of mature blood cells, while the
      nonhematopoietic component includes osteoblasts/osteoclasts, endothelial cells
      (ECs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs).
      These cells form specialized "niches" which are close to the vasculature
      ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular
      niche", rich in blood vessels where ECs and mural cells (pericytes and smooth
      muscle cells), create a microenvironment affecting the behavior of several stem
      and progenitor cells. The vessel wall acts as an independent niche for the
      recruitment of EPCs and MSCs. This chapter will focus on the description of the
      role of BM niches in the control of angiogenesis occurring during multiple
      myeloma progression.

PMID- 25619719
TI  - Biogenesis and function of the NGF/TrkA signaling endosome.
AB  - Target-derived neurotrophin nerve growth factor (NGF) and its receptor TrkA are
      well known for retrograde signaling to promote survival and innervation of
      sympathetic and sensory neurons. In recent years, the signaling endosome model
      has been used to describe the sustained NGF/TrkA retrograde signaling as a
      process of endocytosis and retrograde transport of NGF/TrkA-containing endosomes
      from the axon terminal to the cell body for activation of NGF-inducible gene
      expression responsible for neuronal survival and development. Here, we review the
      biogenesis and function of NGF, TrkA, and the signaling endosome and discuss
      possible roles of Rab GTPases in the biogenesis and trafficking of signaling
      endosomes. 

PMID- 25619721
TI  - Enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA on human
      brain metastatic breast cancer.
AB  - Novel molecularly targeted agents that block the development and metastasis of
      human brain metastatic breast cancer hold great promise for their translational
      value. In this study, we constructed a novel targeting composite peptide BRBP1
      TAT-KLA comprising of three elements: a brain metastatic breast carcinoma cell
      (231-BR)-binding peptide BRBP1, a cell penetrating peptide TAT, and a
      proapoptotic peptide KLA. This composite peptide efficiently internalized in 231
      BR cells and consequently induced mitochondrial damage and cellular apoptosis.
      Exposure of 231-BR cells to BRBP1-TAT-KLA significantly decreased cell viability
      and increased apoptosis compared with the cells treated with the control
      peptides. In vivo relevance of these findings was further corroborated in the 231
      BR tumor-bearing mice that demonstrated significantly delayed tumor development
      and metastasis following administration of BRBP1-TAT-KLA compared with those
      treated with TAT-KLA alone. Interestingly, BRBP1-TAT-KLA inhibited the formation
      of both large and micro-metastases, while TAT-KLA alone failed to significantly
      reduce micro-metastases in the breast cancer brain metastasis mice. BRBP1-TAT-KLA
      selectively homed to the tumors in vivo where it induced cellular apoptosis
      without significant toxicity on non-tumor tissues. Our findings therefore
      demonstrated the enhanced antitumor effects of the BRBP1 compound peptide BRBP1
      TAT-KLA, providing insights toward development of a potential therapeutic
      strategy for brain metastatic breast cancer. 

PMID- 25619722
TI  - Pulmonary tumor embolus with high (18)FDG uptake mimicking lung metastasis from
      renal-cell cancer.

PMID- 25619723
TI  - Paracrine factors of human fetal MSCs inhibit liver cancer growth through reduced
      activation of IGF-1R/PI3K/Akt signaling.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      in the world. The multikinase inhibitor sorafenib only demonstrated marginal
      improvement in overall survival for advanced disease prompted the search for
      alternative treatment options. Human mesenchymal stem cells (MSCs) have the
      ability to home to tumor cells. However, its functional roles on the tumor
      microenvironment remain controversial. Herein, we showed that conditioned media
      derived from human fetal MSC (CM-hfMSCs) expressed high level of the insulin
      growth factor binding proteins IGFBPs and can sequester free insulin-like growth
      factors (IGFs) to inhibit HCC cell proliferation. The inhibitory effect of IGFBPs
      on IGF signaling was further evident from the reduction of activated IGF-1R and
      PI3K/Akt, leading eventually to the induction of cell cycle arrest. We also
      demonstrated that CM-hfMSCs could enhance the therapeutic efficacy of sorafenib
      and sunitinib. To the best of our knowledge, this is the first report to show
      that CM-hfMSCs has a tumor-specific, antiproliferative effect that is not
      observed with normal human hepatocyte cells and patient-derived matched normal
      tissues. Our results thus suggest that CM-hfMSCs can provide a useful tool to
      design alternative/adjuvant treatment strategies for HCC, especially in related
      function to potentiate the effects of chemotherapeutic drugs. 

PMID- 25619724
TI  - BRAF- and MEK-Targeted Small Molecule Inhibitors Exert Enhanced Antimelanoma
      Effects in Combination With Oncolytic Reovirus Through ER Stress.
AB  - Reovirus type 3 (Dearing) (RT3D) infection is selective for cells harboring a
      mutated/activated RAS pathway. Therefore, in a panel of melanoma cell lines
      (including RAS mutant, BRAF mutant and RAS/BRAF wild-type), we assessed
      therapeutic combinations that enhance/suppress ERK1/2 signaling through use of
      BRAF/MEK inhibitors. In RAS mutant cells, the combination of RT3D with the BRAF
      inhibitor PLX4720 (paradoxically increasing ERK1/2 signaling in this context) did
      not enhance reoviral cytotoxicity. Instead, and somewhat surprisingly, RT3D and
      BRAF inhibition led to enhanced cell kill in BRAF mutated cell lines. Likewise,
      ERK1/2 inhibition, using the MEK inhibitor PD184352, in combination with RT3D
      resulted in enhanced cell kill in the entire panel. Interestingly, TCID50 assays
      showed that BRAF and MEK inhibitors did not affect viral replication. Instead,
      enhanced efficacy was mediated through ER stress-induced apoptosis, induced by
      the combination of ERK1/2 inhibition and reovirus infection. In vivo, combined
      treatments of RT3D and PLX4720 showed significantly increased activity in BRAF
      mutant tumors in both immune-deficient and immune-competent models. These data
      provide a strong rationale for clinical translation of strategies in which RT3D
      is combined with BRAF inhibitors (in BRAF mutant melanoma) and/or MEK inhibitors
      (in BRAF and RAS mutant melanoma). 

PMID- 25619725
TI  - Repair of rhodopsin mRNA by spliceosome-mediated RNA trans-splicing: a new
      approach for autosomal dominant retinitis pigmentosa.
AB  - The promising clinical results obtained for ocular gene therapy in recent years
      have paved the way for gene supplementation to treat recessively inherited forms
      of retinal degeneration. The situation is more complex for dominant mutations, as
      the toxic mutant gene product must be removed. We used spliceosome-mediated RNA
      trans-splicing as a strategy for repairing the transcript of the rhodopsin gene,
      the gene most frequently mutated in autosomal dominant retinitis pigmentosa. We
      tested 17 different molecules targeting the pre-mRNA intron 1, by transient
      transfection of HEK-293T cells, with subsequent trans-splicing quantification at
      the transcript level. We found that the targeting of some parts of the intron
      promoted trans-splicing more efficiently than the targeting of other areas, and
      that trans-splicing rate could be increased by modifying the replacement
      sequence. We then developed cell lines stably expressing the rhodopsin gene, for
      the assessment of phenotypic criteria relevant to the pathogenesis of retinitis
      pigmentosa. Using this model, we showed that trans-splicing restored the correct
      localization of the protein to the plasma membrane. Finally, we tested our best
      candidate by AAV gene transfer in a mouse model of retinitis pigmentosa that
      expresses a mutant allele of the human rhodopsin gene, and demonstrated the
      feasibility of trans-splicing in vivo. This work paves the way for trans-splicing
      gene therapy to treat retinitis pigmentosa due to rhodopsin gene mutation and,
      more generally, for the treatment of genetic diseases with dominant transmission.

PMID- 25619726
TI  - Phase 1 Trial of Bi-shRNA STMN1 BIV in Refractory Cancer.
AB  - Stathmin1 (STMN1) is a microtubule modulator that is expressed in multiple
      cancers and correlates with poor survival. We previously demonstrated in vivo
      safety of bifunctional (bi) shRNA STMN1 bilamellar invaginated vesicle (BIV) and
      that systemic delivery correlated with antitumor activity. Patients with
      superficial advanced refractory cancer with no other standard options were
      entered into trial. Study design involved dose escalation (four patients/cohort)
      using a modified Fibonacci schema starting at 0.7 mg DNA administered via single
      intratumoral injection. Biopsy at baseline, 24/48 hours and resection 8 days
      after injection provided tissue for determination of cleavage product using next
      generation sequencing (NGS) and reverse transcription quantitative polymerase
      chain reaction (RT-qPCR), 5' RLM rapid amplification of cDNA ends (RACE) assay.
      Serum pharmacokinetics of circulating plasmid was done. Twelve patients were
      entered into three dose levels (0.7, 1.4, 7.0 mg DNA). No >= grade 3 toxic
      effects to drug were observed. Maximum circulating plasmid was detected at 30
      seconds with less than 10% detectable in all subjects at 24 hours. No toxic
      effects were observed. Predicted cleavage product was detected by both NGS (n =
      7/7 patients analyzed, cohorts 1, 2) and RLM RACE (n = 1/1 patients analyzed
      cohort 3). In conclusion, bi-shRNA STMN1 BIV is well tolerated and detection of
      mRNA target sequence-specific cleavage product confirmed bi-shRNA BIV mechanism
      of action. 

PMID- 25619727
TI  - Facts and myths of cerebrospinal fluid pressure for the physiology of the eye.
AB  - The orbital cerebrospinal fluid pressure (CSFP) represents the true counter
      pressure against the intraocular pressure (IOP) across the lamina cribrosa and
      is, therefore, one of the two determinants of the trans-lamina cribrosa pressure
      difference (TLPD). From this anatomic point of view, an elevated TLPD could be
      due to elevated IOP or abnormally low orbital CSFP. Both experimental and
      clinical studies have suggested that a low CSFP could be associated with
      glaucomatous optic neuropathy in normal-pressure glaucoma. These included monkey
      studies with an experimental long-term reduction in CSFP, and clinical
      retrospective and prospective studies on patients with normal-pressure glaucoma.
      Since the choroidal blood drains via the vortex veins through the superior
      ophthalmic vein into the intracranial cavernous sinus, anatomy suggests that the
      CSFP could influence choroidal thickness. A population-based study revealed that
      thicker subfoveal choroidal thickness was associated with higher CSFP. Since the
      central retinal vein passes through the orbital CSF space, anatomy suggests that
      the retinal venous pressure should be at least as high as the orbital CSFP. Other
      experimental, clinical or population-based studies suggested an association
      between higher CSFP and higher retinal venous pressure and wider retinal veins.
      Consequently, a higher estimated CSFP was associated with arterial hypertensive
      retinopathy (with respect to the dilated retinal vein diameter and higher
      arterial-to-venous diameter) and with the prevalence, severity and incidence of
      diabetic retinopathy. Physiologically, CSFP was related with higher IOP. The
      influence of the CSFP on the episcleral venous pressure and/or a regulation of
      both CSFP and IOP by a center in the dorsomedial/perifornical hypothalamus may be
      responsible for this. In summary, the CSFP may be an overlooked parameter in
      ocular physiology and pathology. Abnormal changes in the CSFP, in particular in
      relationship to the IOP, may have pathophysiologic importance. 

PMID- 25619728
TI  - Bone augmentation for revision total ankle arthroplasty with large bone defects.

PMID- 25619729
TI  - Misfit-layered Bi1.85 Sr2 Co1.85 O7.7-delta for the hydrogen evolution reaction:
      beyond van der Waals heterostructures.
AB  - Recent research on stable 2D nanomaterials has led to the discovery of new
      materials for energy-conversion and energy-storage applications. A class of
      layered heterostructures known as misfit-layered chalcogenides consists of well
      defined atomic layers and has previously been applied as thermoelectric materials
      for use as high-temperature thermoelectric batteries. The performance of such
      misfit-layered chalcogenides in electrochemical applications, specifically the
      hydrogen evolution reaction, is currently unexplored. Herein, a misfit-layered
      chalcogenide consisting of CoO2 layers interleaved with an SrO-BiO-BiO-SrO rock
      salt block and having the formula Bi1.85 Sr2 Co1.85 O7.7-delta is synthesized and
      examined for its structural and electrochemical properties. The hydrogen
      evolution performance of misfit-layered Bi1.85 Sr2 Co1.85 O7.7-delta , which has
      an overpotential of 589 mV and a Tafel slope of 51 mV per decade, demonstrates
      the promising potential of misfit-layered chalcogenides as electrocatalysts
      instead of classical carbon. 

PMID- 25619730
TI  - Coupling carbon nanotube film microextraction with desorption corona beam
      ionization for rapid analysis of Sudan dyes (I-IV) and Rhodamine B in chilli oil.
AB  - A rapid analysis method by coupling carbon nanotube film (CNTF) microextraction
      with desorption corona beam ionization (DCBI) was developed for the determination
      of Sudan dyes (I-IV) and Rhodamine B in chilli oil samples. Typically, CNTF was
      immersed into the diluted solution of chilli oil for extraction, which was then
      placed directly under the visible plasma beam tip of the DCBI source for
      desorption and ionization. Under optimized conditions, five dyes were
      simultaneously determined using this method. Results showed that the analytes
      were enriched by the CNTF through the pi-pi interactions, and the proposed method
      could significantly improve the sensitivities of these compounds, compared to the
      direct analysis by DCBI-MS/MS. The method with a linear range of 0.08-12.8 MUg g(
      1) and good linear relationships (R(2) > 0.93) in a multiple reaction monitoring
      (MRM) mode was developed. Satisfactory reproducibility was achieved. Relative
      standard deviations (RSDs) were less than 20.0%. The recoveries ranged from 80.0
      to 110.0%, and the limits of detection (LODs) were in the range of 1.4-21 ng g(
      1). Finally, the feasibility of the method was further exhibited by the
      determination of five illegal dyes in chilli powder. These results demonstrate
      that the proposed method consumes less time and solvent than conventional HPLC
      based methods and avoids the contamination of chromatographic column and ion
      source from non-volatile oil. With the help of a 72-well shaker, multiple samples
      could be treated simultaneously, which ensures high throughput for the entire
      pretreatment process. In conclusion, it provides a rapid and high-throughput
      approach for the determination of such illicit additions in chilli products. 

PMID- 25619732
TI  - 6-Methoxy-5-phosphaphenanthrene: a molecule with an unreactive P=C double bond.
AB  - A multi-step synthesis of the title compound has been devised. In spite of its
      P=C double bond, the compound does not react at 100  degrees C with methanol and
      2,3-dimethyl-1,3-butadiene. DFT calculations indicate a planar core, a long P=C
      double bond at 1.725 A and a high-lying LUMO. Complexation can force the methoxy
      substituent to rotate out of the plane, thus restoring partly the double bond
      character of the P=C bond.

PMID- 25619731
TI  - Dopamine depletion of the striatum causes a cell-type specific reorganization of
      GluN2B- and GluN2D-containing NMDA receptors.
AB  - The GluN2B subunit of NMDA receptors (NMDARs) is an attractive drug target for
      therapeutic intervention in Parkinson's disease (PD). We have used whole-cell
      patch clamp recordings in brain slices to examine the contribution of GluN2B and
      GluN2D to functional NMDARs in the striatum of the unilateral 6-hydroxydopamine
      lesioned mouse model of PD. We found that current/voltage relationships of NMDAR
      mediated excitatory post synaptic currents were altered in a population of medium
      spiny projection neurons (MSNs) in the dopamine-depleted striatum. Using
      antagonists for GluN2B- and GluN2D-containing NMDARs, we found that GluN2B
      contributes to functional NMDARs in MSNs in the intact striatum and in the
      striatum of control mice. The function of GluN2B-containing NMDARs is however
      reduced in MSNs from the dopamine-depleted striatum. GluN2D is absent in MSNs
      from intact striatum and from control mice, but the contribution of this subunit
      to functional NMDARs is increased in the dopamine-depleted striatum. These
      changes in the subunit composition of NMDARs are associated with a decreased
      protein level of GluN2B and an increased level of GluN2D in the dopamine-depleted
      striatum. In cholinergic interneurons from the intact striatum and control mice,
      both GluN2B and GluN2D contribute to functional NMDARs. The functions of GluN2D,
      and to some extent GluN2B, are reduced in the dopamine-depleted striatum. Our
      findings demonstrate a cell-type specific reorganization of GluN2B and GluN2D in
      a mouse model of PD and suggest GluN2D as a potential target for the management
      of the disease. 

PMID- 25619733
TI  - Effects of homocysteine on mesenchymal cell proliferation and differentiation
      during chondrogenesis on limb development.
AB  - High levels of homocysteine (Hcy) are related to an increased risk of the
      occurrence of congenital anomalies, including limb defects. However, few
      evaluations about how toxic levels of Hcy affect limb development have been
      reported. We investigated whether Hcy can affect the cell cycle proteins and
      proteins involved in mesenchymal cell differentiation during limb development, in
      a chicken embryo model. Embryos were treated with 20 umol d-l Hcy/50 ul saline at
      embryonic day 2 and analyzed at embryonic day 6. Untreated control embryos
      received exclusively 50 ul saline solution. To identify cells in proliferation
      and cell cycle proteins, as well as Pax1/9 and Sox9 proteins, we performed
      immunolocalization and flow cytometry analyses using the antibodies anti
      phosphohistone H3, anti-p53, anti-p21, anti-proliferating cell nuclear antigen,
      anti-Pax1, anti-Pax9 and anti-Sox9. No significant differences in cell
      proliferation were observed between Hcy-treated and untreated embryos. We
      observed a decrease of the proliferating cell nuclear antigen and p21 proteins,
      both involved in the G1 phase of cell cycle progression. On the other hand, in
      mesenchymal cells of the limbs, Hcy induces an increase of p53 protein, which can
      be activated by DNA damage. In cell differentiation, Hcy induced an increase
      mainly of Pax9 and Sox9 proteins. Our data indicate that the treatment with Hcy
      changes the mesenchymal cell dynamics during limb development, but does not
      change the morphology of the cartilage molds. These findings provide information
      to understand better the cellular basis of the toxicity of Hcy on chondrogenesis
      during limb development.

PMID- 25619734
TI  - Trends in head and neck cancers in England from 1995 to 2011 and projections up
      to 2025.
AB  - BACKGROUND: The magnitude of the growing burden of oropharyngeal cancers (OPC), a
      sub-set of head and neck cancers (HNC), is unknown in England. METHODS: Data were
      extracted from population-based cancer registries in England. The burden of HNC
      overall and by anatomic site was described from 1995 to 2011. Projections of
      future rates up to 2025 were estimated using flexible age-period-cohort
      modelling. RESULTS: HNC increased by 59% between 1995 and 2011 in England.
      Projections indicate that the number of HNC cases will increase by 55% from 2011,
      totalling 11,748 new cases in 2025, ranking HNC as the sixth most common cancer.
      Of the anatomic sites, OPC is projected to account for 35% of HNC with the
      largest rate increase (annual percentage change, +7.3% for men and +6.2% for
      women between 2011 and 2025), predominantly affecting males <60years. This
      projected burden is equivalent to a 239% increase in number of OPC cases.
      Incidence of the oral cavity, salivary glands and palate are projected to rise at
      lower rates, whereas rates of the nasopharynx, hypopharynx and larynx remain
      relatively stable or decreasing. CONCLUSION: The substantial recent and predicted
      future significant increase in OPC highlights the need for prioritising the
      provision of cancer services for the considerable burden of OPC patients and
      survivors and cancer control strategies.

PMID- 25619735
TI  - (18)FDG-PET/CT for the detection of regional nodal metastasis in patients with
      head and neck cancer: a meta-analysis.
AB  - We performed a meta-analysis to evaluate the role of (18)FDG-PET/CT for detection
      of regional nodal metastasis in patients with head and neck cancer (HNC). Studies
      about (18)FDG-PET/CT were systematically searched in the MEDLINE and EMBASE
      databases. The Stata software was used to obtain pooled estimates of sensitivity,
      specificity, positive likelihood ratio, and negative likelihood ratio for (18)FDG
      PET/CT. We also compared the performance of (18)FDG-PET/CT with that of
      conventional imaging (CT, MRI, and CT/MRI) by analyzing studies that had also
      used conventional imaging on the same patients. 24 articles bulled all inclusion
      criteria (1270 patients). The pooled per-patient, per-neck-side, and per-neck
      level sensitivities/specificities for (18)FDG-PET/CT were 0.91/0.87, 0.84/0.83,
      and 0.80/0.96, respectively. Across 13 studies (3460 neck levels) with per-neck
      level data, the sensitivity and specificity of PET-CT were 0.84 and 0.96, and of
      conventional imaging were 0.63 and 0.96, respectively. (18)FDG-PET/CT has good
      diagnostic performance for the detection of regional nodal metastasis in HNC
      patients. Compared with conventional imaging, (18)FDG-PET/CT may have higher per
      neck-level sensitivity.

PMID- 25619737
TI  - Non-equilibrium thermodynamical description of rhythmic motion patterns of active
      systems: a canonical-dissipative approach.
AB  - We derive explicit expressions for the non-equilibrium thermodynamical variables
      of a canonical-dissipative limit cycle oscillator describing rhythmic motion
      patterns of active systems. These variables are statistical entropy, non
      equilibrium internal energy, and non-equilibrium free energy. In particular, the
      expression for the non-equilibrium free energy is derived as a function of a
      suitable control parameter. The control parameter determines the Hopf bifurcation
      point of the deterministic active system and describes the effective pumping of
      the oscillator. In analogy to the equilibrium free energy of the Landau theory,
      it is shown that the non-equilibrium free energy decays as a function of the
      control parameter. In doing so, a similarity between certain equilibrium and non
      equilibrium phase transitions is pointed out. Data from an experiment on human
      rhythmic movements is presented. Estimates for pumping intensity as well as the
      thermodynamical variables are reported. It is shown that in the experiment the
      non-equilibrium free energy decayed when pumping intensity was increased, which
      is consistent with the theory. Moreover, pumping intensities close to zero could
      be observed at relatively slow intended rhythmic movements. In view of the Hopf
      bifurcation underlying the limit cycle oscillator model, this observation
      suggests that the intended limit cycle movements were actually more similar to
      trajectories of a randomly perturbed stable focus. 

PMID- 25619736
TI  - Persistent DNA damage-induced premature senescence alters the functional features
      of human bone marrow mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) are adult multipotent stem cells located in
      various tissues, including the bone marrow. In contrast to terminally
      differentiated somatic cells, adult stem cells must persist and function
      throughout life to ensure tissue homeostasis and repair. For this reason, they
      must be equipped with DNA damage responses able to maintain genomic integrity
      while ensuring their lifelong persistence. Evaluation of hMSC response to
      genotoxic insults is of great interest considering both their therapeutic
      potential and their physiological functions. This study aimed to investigate the
      response of human bone marrow MSCs to the genotoxic agent Actinomycin D (ActD), a
      well-known anti-tumour drug. We report that hMSCs react by undergoing premature
      senescence driven by a persistent DNA damage response activation, as hallmarked
      by inhibition of DNA synthesis, p21 and p16 protein expression, marked Senescent
      Associated beta-galactosidase activity and enlarged gammaH2AX foci co-localizing
      with 53BP1 protein. Senescent hMSCs overexpress several senescence-associated
      secretory phenotype (SASP) genes and promote motility of lung tumour and
      osteosarcoma cell lines in vitro. Our findings disclose a multifaceted
      consequence of ActD treatment on hMSCs that on the one hand helps to preserve
      this stem cell pool and prevents damaged cells from undergoing neoplastic
      transformation, and on the other hand alters their functional effects on the
      surrounding tissue microenvironment in a way that might worsen their tumour
      promoting behaviour. 

PMID- 25619740
TI  - Re: Benign and malignant disease of the clivus.

PMID- 25619739
TI  - Targeted therapy for chronic lymphocytic leukemia: current status and future
      directions.
AB  - The majority of patients with chronic lymphocytic leukemia (CLL) respond to chemo
      immunotherapy. However, long-term remission remains elusive and the majority of
      patients will die of complications related to CLL. In this review we discuss the
      recent developments in targeted therapy for CLL. Targeted therapy has evolved
      beyond the cell surface targeting of CD20 with rituximab. Our review focuses on
      the evolution of antibody therapy in CLL, strategies to target effector T cells
      to the tumor, inhibition of the B-cell receptor signaling pathway, and finally
      targeting the mediators of apoptosis. With our improved understanding of the
      biology of CLL, the evolution of targeted therapy has resulted in significant
      clinical responses in patients who are refractory to traditional treatment
      options and holds the potential for a future where we can manage this disease
      without chemotherapy. 

PMID- 25619742
TI  - Design and Biological Evaluation of Furan/Pyrrole/Thiophene-2-carboxamide
      Derivatives as Efficient DNA GyraseB Inhibitors of Staphylococcus aureus.
AB  - DNA topoisomerases are well-validated targets in micro-organisms. DNA gyraseB is
      one of the most important enzymes among them as per their clinical importance. In
      earlier study, a novel lead 4-((4-(furan-2-carboxamido)phenyl)amino)-4
      oxobutanoic acid was identified as inhibitor against DNA gyraseB with an IC50 of
      12.88 +/- 1.39 MUm. Subsequently, analogues of this lead were developed and
      evaluated through in vitro assays and in vivo studies. Among the 24 analogues,
      compound 22 was found to be the top hit with an improved DNA gyraseB activity of
      5.35 +/- 0.61 MUm, and the binding affinity of this compound was further
      ascertained biophysically through differential scanning fluorimetry. The most
      potent ligand did not show any signs of cardiotoxicity in zebra fish ether-ago-go
      related gene, ascertaining the safety profile of this series a breakthrough among
      the previously reported cardiotoxic gyraseB inhibitors. 

PMID- 25619743
TI  - Definition of the transcription factor TdIF1 consensus-binding sequence through
      genomewide mapping of its binding sites.
AB  - TdIF1 was originally identified as a protein that directly binds to terminal
      deoxynucleotidyltransferase, TdT. Through in vitro selection assays (SELEX), we
      recently showed that TdIF1 recognizes both AT-tract and a specific DNA sequence
      motif, 5'-TGCATG-3', and can up-regulate the expression of RAB20 through the
      latter motif. However, whether TdIF1 binds to these sequences in the cells has
      not been clear and its other target genes remain to be identified. Here, we
      determined in vivo TdIF1-binding sequences (TdIF1-invivoBMs) on the human
      chromosomes through ChIP-seq analyses. The result showed a 160-base pair cassette
      containing 'AT-tract~palindrome (inverted repeat)~AT-tract' as a likely target
      sequence of TdIF1. Interestingly, the core sequence of the palindrome in the
      TdIF1-invivoBMs shares significant similarity to the above 5'-TGCATG-3' motif
      determined by SELEX in vitro. Furthermore, spacer sequences between AT-tract and
      the palindrome contain many potential transcription factor binding sites. In
      luciferase assays, TdIF1 can up-regulate transcription activity of the promoters
      containing the TdIF1-invivoBM, and this effect is mainly through the palindrome.
      Clusters of this motif were found in the potential target genes. Gene ontology
      analysis and RT-qPCR showed the enrichment of some candidate targets of TdIF1
      among the genes involved in the regulation of ossification. Potential modes of
      transcription activation by TdIF1 are discussed. 

PMID- 25619744
TI  - Fabrication of multicomponent polymer nanostructures containing PMMA shells and
      encapsulated PS nanospheres in the nanopores of anodic aluminum oxide templates.
AB  - Multi-component polymer nanomaterials have attracted great attention because of
      their applications in areas such as biomedicine, tissue engineering, and organic
      solar cells. The precise control over the morphologies of multi-component polymer
      nanomaterials, however, is still a great challenge. In this work, the fabrication
      of poly(methyl methacrylate)(PMMA)/poly-styrene (PS) nanostructures that contain
      PMMA shells and encapsulated PS nanospheres is studied. The nanostructures are
      prepared using a triple solution wetting method with anodic aluminum oxide (AAO)
      templates. The nanopores of the templates are wetted sequentially by PS solutions
      in dimethylformamide (DMF), PMMA solutions in acetic acid, and water. The
      compositions and morphologies of the nanostructures are controlled by the
      interactions between the polymers, solvents, and AAO walls. This work not only
      presents a feasible method to prepare multi-component polymer nanomaterials, but
      also leads to a better understanding of polymer-solvent interactions in confined
      geometries. 

PMID- 25619745
TI  - Lethal sepsis and malignant transformation in severe congenital neutropenia:
      report from the Italian Neutropenia Registry.

PMID- 25619746
TI  - Rapid turbidimetric assay to potency evaluation of tigecycline in lyophilized
      powder.
AB  - Tigecycline, a first-in-class glycylcycline and an analog of the semisynthetic
      antibiotic minocycline, is a potent, broad-spectrum antibiotic that acts by the
      inhibition of protein translation in bacteria. This glycylcycline inhibits Gram
      positive, Gram-negative, atypical, anaerobic and antibiotic-resistant organisms.
      There is no microbiological analytical method for tigecycline in lyophilized
      powder reported yet. Thus, this paper reports the development and validation of a
      simple, sensitive, accurate and reproducible turbidimetric method to quantify
      tigecycline in lyophilized powder, using Staphylococcus aureus as microorganism
      test and 3*3 parallel line assay design, with twenty tubes for each assay. The
      validated method showed good results of linearity in the concentration range from
      3 to 4.32MUg/mL (r(2)=0.9999), selectivity, precision, robustness and accuracy of
      99.74%. The results demonstrated the validity of the proposed bioassay, which
      allows reliable quantitation of tigecycline in pharmaceutical samples and
      therefore can be used as a useful alternative methodology for the routine quality
      control of this medicine. 

PMID- 25619747
TI  - Physicochemical characterization of pure persimmon juice: nutritional quality and
      food acceptability.
AB  - Technological process for production of non-astringent persimmon (Diospyros kaki
      Thunb. cv. "Rojo Brillante") juice was described. The degree of fruit ripening
      expressed as color index (CI) varied between 12.37 and 16.33. Persimmon juice was
      characterized by determining physicochemical quality parameters as yield, total
      soluble solids (TSS), pH, titratable acidity (TA), organic acids, and main
      sugars. A thermal treatment of 90 oC for 10 s was effective in controlling
      naturally occurring microorganisms for at least 105 d of storage without
      significantly affecting production of soluble brown pigments (BPs) and 5
      hydroxymethyl furfural (5-HMF), total phenolic compounds (TPC), antioxidant
      capacity and acceptability of juice by panelists. Storage time affected all and
      each of the above parameters, reducing BPs, TPC and antioxidant capacity but
      increasing 5-HMF content. Refrigerated storage enhanced the acceptability of the
      juices. This information may be used by the juice industry as a starting point
      for production of pure persimmon juices. 

PMID- 25619748
TI  - Impact of the contamination level and the background flora on the growth of
      Listeria monocytogenes in ready-to-eat diced poultry.
AB  - The food safety criteria that have been incorporated in European regulation (EC)
      No2073/2005 (Official Journal of the European Union L, 338, 2005, 1), for
      Listeria monocytogenes in ready-to eat (RTE) foods, specify a maximum allowable
      concentration of 100 CFU g(-1) or ml(-1) . Some factors such as pH, salt and
      modified atmosphere packaging (MAP) are used to prevent the growth of L.
      monocytogenes in order to comply with the limit. Interactions between background
      microflora (BM) and L. monocytogenes may limit the growth of L. monocytogenes.
      The aim of this study was to investigate the mechanisms behind the observed
      inhibition by natural BM of the growth of L. monocytogenes in ready-to-eat diced
      poultry meat whose pH and water activity were favourable to its growth. The
      dynamics of L. monocytogenes and natural BM were therefore monitored in mono
      culture and co-culture experiments with various combinations of contamination
      levels. In the absence of BM, the growth potential of L. monocytogenes depended
      only on the initial inoculum. With both BM and L. monocytogenes, whatever the
      combination of concentrations studied, the growth potentials of L. monocytogenes
      were lower than in a mono-culture through a partial Jameson effect. Thus, the use
      by date of this product can be optimized by using models that take into account
      interactions with BM. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of the
      growth of Listeria monocytogenes in a diced poultry meat, a matrix whose pH and
      water activity characteristics are favourable to L. monocytogenes growth, showed
      that it was inhibited by natural background microflora. This highlights the
      importance of knowing the product's composition, and in particular the natural
      background microflora, which can impact the use-by date.

PMID- 25619749
TI  - Withdrawn: Aplastic Anemia: Alternative Immunosuppressive Treatments and
      Eltrombopag. A report from the 2014 EBMT Educational Meeting from the Severe
      Aplastic Anaemia and Infectious Diseases Working Parties.
AB  - Withdrawn by the publisher.

PMID- 25619750
TI  - The Role of JNK Signalling in Responses to Oxidative DNA Damage.
AB  - The production of reactive oxygen species is a normal part of cell physiology,
      but many internal and external stimuli are able to trigger the production of
      excess levels of oxidants that are potentially damaging. The threat of oxidative
      damage is particularly significant to DNA, as damaged bases can interfere with
      replication to generate lasting mutations. Signalling through the JNK pathway is
      a key cellular response to oxidative damage. Depending on the intensity and
      duration of the damage signal, JNK signalling can lead to distinct alternative
      responses including DNA repair, anti-oxidant production or cell death. These
      responses are highly relevant to cancer therapy, as tumours are often under
      oxidative stress that produces elevated JNK levels and therapy often involves
      inducing DNA damage with the intention of driving cell death. In this review we
      examine the causes and consequences of JNK activation that relate to oxidative
      DNA damage, with a focus on the potential therapeutic implications. 

PMID- 25619751
TI  - Oncotargets in different renal cancer subtypes.
AB  - Renal cell cancer is a heterogeneous group of cancers with different histologic
      subtypes. The majority of renal tumors in adults are clear cell renal cell
      carcinomas, which are characterized by von Hippel- Lindau (VHL) gene alterations.
      Recent advances in defining the genetic landscape of renal cancer has shown the
      genetic heterogeneity of clear cell renal cell carcinomas (ccRCC) and the
      presence of at least 3 additional ccRCC tumor suppressor genes on chromosome 3p.
      Due to inactivation of VHL, renal cancer cells produce the HIF-responsive growth
      factor VEGF. The PI3K--mTORC1 signaling axis also represents a target for
      therapy. The new systemic therapies, including tyrosine kinase inhibitors,
      monoclonal antibodies, and mTOR inhibitors, aim to suppress angiogenesis with
      vascular endothelial growth factor as a target. Various VEGF-inhibitors are
      approved for the treatment of ccRCC and we discuss recent advancements in the
      treatment of metastatic ccRCC. Other gene alterations have been identified in
      hereditary cancer syndromes, e.g. FLCN, TSC1, TSC2, TFE3, TFEB, MITF, FH, SDHB,
      SDHD, MET, and PTEN and we review their role in renal tumor carcinogenesis,
      prognosis, and targeted therapy. By reviewing the associations between
      morphologic features and molecular genetics of renal cancer we provide insight
      into the basis for targeted renal cancer therapy.

PMID- 25619752
TI  - Cardioprotection by Targeting the Pool of Resident and Extracardiac Progenitors.
AB  - The adult heart has the capacity to generate new myocytes that are markedly
      enhanced in acute and chronic heart failure of ischemic and non-ischemic origin.
      In addition, a pool of blood trafficking progenitor cells able to sense
      myocardial damage may home to the sites of injury participating to cardiac
      repair. This new view of myocardial biology leads to an expanding long-term
      research and therapeutic goals for cardioprotection. A fundamental concept to be
      analyzed is whether cardiac diseases are influenced by changes in the properties
      of tissue specific and circulating progenitors. Loss of self-renewal capacity,
      impaired growth or increased susceptibility to death may lead to a reduction of
      progenitors and leave myocardial damage unrepaired. Cardiac progenitors generate
      all myocardial cell lineages, thus impairment in their growth is expected to be
      critically involved in the structural and functional modifications of the heart.
      The fact that, in addition to well known effects of anthracyclines, also new
      drugs that target molecular pathways implicated in cell death and growth can be
      cardiotoxic further supports our hypothesis. Understanding the role of resident
      and extracardiac progenitors in the pathogenesis of cardiomyopathies of different
      etiology will provide not only a better comprehension of cardiac homeostasis but
      will also open new avenues for therapeutic interventions. The progress toward
      effective myocardial regeneration based on exploiting the self-renewal potential
      of the myocardium and the systemic pool of cardiogenic cells should advance the
      likelihood of efficient cardioprotection and restoration of cardiac function. 

PMID- 25619754
TI  - Isolation of Ralstonia solanacearum-infecting bacteriophages from tomato fields
      in Chiang Mai, Thailand, and their experimental use as biocontrol agents.
AB  - AIMS: To isolate and characterize novel bacteriophages infecting the
      phytopathogen, Ralstonia solanacearum, and to evaluate them as resources with
      potential uses in the biocontrol of bacterial wilt. METHODS AND RESULTS: Fourteen
      phages infecting R. solanacearum were isolated from soil samples collected in
      Chiang Mai, Thailand. The phages showed different host ranges when tested against
      59 R. solanacearum strains isolated from Thailand and Japan. These phages were
      characterized as nine podoviruses and five myoviruses based on their morphology.
      Podovirus J2 in combination with another podovirus (phiRSB2) lysed host cells
      very efficiently in contaminated soil. J2 treatment prevented wilting of tomato
      plants infected with a highly virulent R. solanacearum strain. CONCLUSIONS:
      Treatment with J2 effectively reduced the amount of the bacterial wilt pathogen
      in contaminated soil and prevented bacterial wilt of tomato in pot experiments.
      Myovirus J6 possessed jumbo phage features, giving a unique opportunity to study
      its utilization as a biocontrol agent. SIGNIFICANCE AND IMPACT OF THE STUDY: As
      exemplified by J2, the phages isolated in this study represent valuable resources
      with potential uses in biocontrol of bacterial wilt. A rare jumbo phage J6 served
      as a valuable subject to understand and utilize this new group of phages.

PMID- 25619753
TI  - Superantigens in Staphylococcus aureus isolated from prosthetic joint infection.
AB  - Staphylococcus aureus is a common cause of prosthetic joint infection (PJI). The
      prevalence of superantigens (SAgs) among PJI-associated S. aureus is unknown.
      Eighty-four S. aureus isolates associated with PJI isolated between 1999 and 2006
      were studied. SAg genes, sea, seb, sec, sed, see, seg, seh, sei, and tst, were
      assayed by PCR. Seventy-eight (92.9%) isolates carried at least 1 SAg gene
      studied, with 61 (72.6%) harboring more than 1. seg was most commonly (70.2%),
      and seh was least frequently (4.8%) detected. tst-positive isolates were
      associated with early infection and increased erythrocyte sedimentation rate at
      diagnosis (P=0.006 and P=0.021, respectively). seg and sei were associated with
      methicillin resistance (P=0.008 and P=0.002, respectively). A majority of PJI
      associated isolates studied produced biologically active SAgs in both planktonic
      and biofilm growth modes. SAg genes are prevalent in S. aureus causing PJI. 

PMID- 25619755
TI  - Electrospun polycaprolactone matrices with tensile properties suitable for soft
      tissue engineering.
AB  - The extracellular environment is a complex network of functional and structural
      components that impart chemical and mechanical stimuli that affect cellular
      function and fate. Cell differentiation on three dimensional scaffolds is also
      determined by the modulus of the substrate. Electrospun PCL nanofibers, which
      mimic the extra cellular matrix, have been developed with a wide variety of
      solvents and their combinations. The various studies have revealed that the
      solvents used influence the physical and mechanical properties, resulting in
      scaffolds with Young's modulus in the range of 1.8-15.4 MPa, more suitable for
      engineering of hard tissue like bone. The current study describes the use of
      benign binary solvent-generated fibrous scaffolds with a Young's modulus of 36.05
      +/- 13.08 kPa, which is almost 50 times lower than that of scaffolds derived from
      the commonly used solvents, characterized with myoblast, which can be further
      explored for applications in muscle and soft tissue engineering. 

PMID- 25619756
TI  - pH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol)
      and carboxymethyl cellulose for controlled release of the nonsteroidal anti
      inflammatory drug ketorolac tromethamine.
AB  - In this study, we aimed to produce pH-sensitive microspheres for the controlled
      release of the nonsteroidal anti-inflammatory drug, ketorolac tromethamine (KT).
      For this purpose, an interpenetrating polymer network (IPN) of microspheres of
      poly(vinyl alcohol) (PVA)/sodium carboxymethyl cellulose (NaCMC) were prepared,
      based on different formulations using glutaraldehyde (GA) (0.66 M) and
      hydrochloric acid (HCl) (3%, v/v). The preparation conditions of the microspheres
      were optimized by considering the percentage of entrapment efficiency and
      swelling capacity of the microspheres, and their release data. The effects of PVA
      and NaCMC ratio on the release of KT for over a period of 6 h, at three pH values
      (1.2, 6.8, and 7.4), have been discussed. 

PMID- 25619757
TI  - Sequence-specific label-free nucleic acid biosensor for the detection of the
      hepatitis C virus genotype 1a using a disposable pencil graphite electrode.
AB  - In this paper, we demonstrate a simple, sensitive, inexpensive, disposable and
      label-free electrochemical nucleic acid biosensor for the detection of the
      hepatitis C virus genotype 1a (HCV1a). The nucleic acid biosensor was designed
      with the amino-linked inosine-substituted 20-mer probes, which were immobilized
      onto a disposable pencil graphite electrode (PGE) by covalent linking. The
      proposed nucleic acid biosensor was linear in the range of 0.05 and 0.75 MUM,
      exhibiting a limit of detection of 54.9 nM. The single-stranded synthetic PCR
      product analogs of HCV1a were also detected with satisfactory results under
      optimal conditions, showing the potential application of this biosensor. 

PMID- 25619758
TI  - Development and validation of the functional assessment of cancer therapy
      antiangiogenesis subscale.
AB  - The Functional Assessment of Cancer Therapy (FACT)-Antiangiogenesis (AntiA)
      Subscale was developed and validated to enhance treatment decision-making and
      side effect management for patients receiving anti-angiogenesis therapies. Side
      effects related to anti-angiogenesis therapies were identified from the
      literature, clinician input, and patient input. Fifty-nine possible patient
      expressions of side effects were generated. Patient and clinician ratings of the
      importance of these expressions led us to develop a 24-item questionnaire with
      clinical and research potential. To assess the scale's reliability and validity,
      167 patients completed the AntiA Subscale, the Functional Assessment of Cancer
      Therapy-general (FACT-G), the FACT-Kidney Symptom Index (FKSI), the FACIT-Fatigue
      Subscale, the Global Rating of Change Scale (GRC), and the PROMIS Global Health
      Scale. Patient responses to the AntiA were analyzed for internal consistency,
      test-retest reliability, convergent and discriminant validity, and responsiveness
      to change in clinical status. All tested scales were found to have good internal
      consistency reliability (Cronbach's alpha 0.70-0.92). Test-retest reliability was
      also good (0.72-0.88) for total and subscale scores and lower for individual
      items. The total score, subscale scores, and all single items (except nosebleeds)
      significantly differentiated between groups defined by level of side effect
      bother. Evaluation of responsiveness to change in this study was not conclusive,
      suggesting an area for further research. The AntiA is a reliable and valid
      measure of side effects from anti-angiogenesis therapy. 

PMID- 25619759
TI  - Safe patient monitoring is challenging but still feasible in a neonatal intensive
      care unit with single family rooms.
AB  - AIM: Patient monitoring generates a large number of alarms. The aim of this study
      was to evaluate the rate, type and management of alarms and to determine the
      risks of a distributed alarm system in a neonatal intensive care unit (NICU) with
      single family rooms. METHODS: A risk analysis was performed before
      implementation. Alarms from patient monitors recorded for a year were identified,
      classified and counted. The first alarms, which went to the nurse responsible for
      the patient, were distinguished from the repeat alarms that were generated if the
      nurse failed to respond within 45 sec. RESULTS: The alarm handling protocol was
      changed as staff felt they needed a greater overview of the NICU alarms to avoid
      risks. In 1 year, 222 751 critical alarms including 12 309 repeat alarms were
      generated by patient monitors, equivalent to two alarms per patient per hour.
      Most of the alarms were oxygen desaturation alarms, followed by bradycardia
      alarms. About 3% of the desaturation alarms and 0.2% of the bradycardia alarms
      were repeated. CONCLUSION: Safe patient monitoring was challenging in a NICU with
      single family rooms, but possible by employing a distributed alarm system. The
      low number of repeat alarms indicated quick response times.

PMID- 25619760
TI  - Sec24 is a coincidence detector that simultaneously binds two signals to drive ER
      export.
AB  - BACKGROUND: Incorporation of secretory proteins into ER-derived vesicles involves
      recognition of cytosolic signals by the COPII coat protein, Sec24. Additional
      cargo diversity is achieved through cargo receptors, which include the
      Erv14/Cornichon family that mediates export of transmembrane proteins despite the
      potential for such clients to directly interact with Sec24. The molecular
      function of Erv14 thus remains unclear, with possible roles in COPII binding,
      membrane domain chaperoning, and lipid organization. RESULTS: Using a targeted
      mutagenesis approach to define the mechanism of Erv14 function, we identify
      conserved residues in the second transmembrane domain of Erv14 that mediate
      interaction with a subset of Erv14 clients. We further show that interaction of
      Erv14 with a novel cargo-binding surface on Sec24 is necessary for efficient
      trafficking of all of its clients. However, we also determine that some Erv14
      clients also directly engage an adjacent cargo-binding domain of Sec24,
      suggesting a novel mode of dual interaction between cargo and coat. CONCLUSIONS:
      We conclude that Erv14 functions as a canonical cargo receptor that couples
      membrane proteins to the COPII coat, but that maximal export requires a bivalent
      signal that derives from motifs on both the cargo protein and Erv14. Sec24 can
      thus be considered a coincidence detector that binds simultaneously to multiple
      signals to drive packaging of polytopic membrane proteins. This mode of dual
      signal binding to a single coat protein might serve as a general mechanism to
      trigger efficient capture, or may be specifically employed in ER export to
      control deployment of nascent proteins.

PMID- 25619761
TI  - Current-oriented swimming by jellyfish and its role in bloom maintenance.
AB  - Cross-flows (winds or currents) affect animal movements [1-3]. Animals can
      temporarily be carried off course or permanently carried away from their
      preferred habitat by drift depending on their own traveling speed in relation to
      that of the flow [1]. Animals able to only weakly fly or swim will be the most
      impacted (e.g., [4]). To circumvent this problem, animals must be able to detect
      the effects of flow on their movements and respond to it [1, 2]. Here, we show
      that a weakly swimming organism, the jellyfish Rhizostoma octopus, can orientate
      its movements with respect to currents and that this behavior is key to the
      maintenance of blooms and essential to reduce the probability of stranding. We
      combined in situ observations with first-time deployment of accelerometers on
      free-ranging jellyfish and simulated the behavior observed in wild jellyfish
      within a high-resolution hydrodynamic model. Our results show that jellyfish can
      actively swim countercurrent in response to current drift, leading to significant
      life-history benefits, i.e., increased chance of survival and facilitated bloom
      formation. Current-oriented swimming may be achieved by jellyfish either directly
      detecting current shear across their body surface [5] or indirectly assessing
      drift direction using other cues (e.g., magnetic, infrasound). Our coupled
      behavioral-hydrodynamic model provides new evidence that current-oriented
      swimming contributes to jellyfish being able to form aggregations of hundreds to
      millions of individuals for up to several months, which may have substantial
      ecosystem and socioeconomic consequences [6, 7]. It also contributes to improve
      predictions of jellyfish blooms' magnitude and movements in coastal waters.

PMID- 25619762
TI  - The lamprey pallium provides a blueprint of the mammalian motor projections from
      cortex.
AB  - BACKGROUND: The frontal lobe control of movement in mammals has been thought to
      be a specific function primarily related to the layered neocortex with its
      efferent connections. In contrast, we now show that the same basic organization
      is present even in one of the phylogenetically oldest vertebrates, the lamprey.
      RESULTS: Stimulation of specific sites in the pallium/cortex evokes eye, trunk,
      locomotor, or oral movements. The pallial projection neurons target brainstem
      motor centers and basal ganglia subnuclei and have prominent dendrites extending
      into the outer molecular layer. They exhibit the characteristic features of
      pyramidal neurons and elicit monosynaptic glutamatergic excitatory postsynaptic
      potentials in output neurons of the optic tectum, reticulospinal neurons, and, as
      shown earlier, basal ganglia neurons. CONCLUSIONS: Our results demonstrate marked
      similarities in the efferent functional connectivity and control of motor
      behavior between the lamprey pallium and mammalian neocortex. Thus, the lamprey
      motor pallium/cortex represents an evolutionary blueprint of the corresponding
      mammalian system.

PMID- 25619763
TI  - A rotary motor drives Flavobacterium gliding.
AB  - Cells of Flavobacterium johnsoniae, a rod-shaped bacterium devoid of pili or
      flagella, glide over glass at speeds of 2-4 MUm/s [1]. Gliding is powered by a
      protonmotive force [2], but the machinery required for this motion is not known.
      Usually, cells move along straight paths, but sometimes they exhibit a reciprocal
      motion, attach near one pole and flip end over end, or rotate. This behavior is
      similar to that of a Cytophaga species described earlier [3]. Development of
      genetic tools for F. johnsoniae led to discovery of proteins involved in gliding
      [4]. These include the surface adhesin SprB that forms filaments about 160 nm
      long by 6 nm in diameter, which, when labeled with a fluorescent antibody [2] or
      a latex bead [5], are seen to move longitudinally down the length of a cell,
      occasionally shifting positions to the right or the left. Evidently, interaction
      of these filaments with a surface produces gliding. To learn more about the
      gliding motor, we sheared cells to reduce the number and size of SprB filaments
      and tethered cells to glass by adding anti-SprB antibody. Cells spun about fixed
      points, mostly counterclockwise, rotating at speeds of 1 Hz or more. The torques
      required to sustain such speeds were large, comparable to those generated by the
      flagellar rotary motor. However, we found that a gliding motor runs at constant
      speed rather than at constant torque. Now, there are three rotary motors powered
      by protonmotive force: the bacterial flagellar motor, the Fo ATP synthase, and
      the gliding motor.

PMID- 25619764
TI  - Targeted conservation to safeguard a biodiversity hotspot from climate and land
      cover change.
AB  - Responses of biodiversity to changes in both land cover and climate are
      recognized [1] but still poorly understood [2]. This poses significant challenges
      for spatial planning as species could shift, contract, expand, or maintain their
      range inside or outside protected areas [2-4]. We examine this problem in Borneo,
      a global biodiversity hotspot [5], using spatial prioritization analyses that
      maximize species conservation under multiple environmental-change forecasts.
      Climate projections indicate that 11%-36% of Bornean mammal species will lose >=
      30% of their habitat by 2080, and suitable ecological conditions will shift
      upslope for 23%-46%. Deforestation exacerbates this process, increasing the
      proportion of species facing comparable habitat loss to 30%-49%, a 2-fold
      increase on historical trends. Accommodating these distributional changes will
      require conserving land outside existing protected areas, but this may be less
      than anticipated from models incorporating deforestation alone because some
      species will colonize high-elevation reserves. Our results demonstrate the
      increasing importance of upland reserves and that relatively small additions
      (16,000-28,000 km(2)) to the current conservation estate could provide
      substantial benefits to biodiversity facing changes to land cover and climate. On
      Borneo, much of this land is under forestry jurisdiction, warranting targeted
      conservation partnerships to safeguard biodiversity in an era of global change.

PMID- 25619766
TI  - Complementary contributions of spike timing and spike rate to perceptual
      decisions in rat S1 and S2 cortex.
AB  - When a neuron responds to a sensory stimulus, two fundamental codes [1-6] may
      transmit the information specifying stimulus identity--spike rate (the total
      number of spikes in the sequence, normalized by time) and spike timing (the
      detailed millisecond-scale temporal structure of the response). To assess the
      functional significance of these codes, we recorded neuronal responses in primary
      (S1) and secondary (S2) somatosensory cortex of five rats as they used their
      whiskers to identify textured surfaces. From the spike trains evoked during
      whisker contact with the texture, we computed the information that rate and
      timing codes carried about texture identity and about the rat's choice. S1 and S2
      spike timing carried more information about stimulus and about choice than spike
      rates; the conjunction of rate and timing carried more information than either
      code alone. Moreover, on trials when our spike-timing-decoding algorithm
      extracted faithful texture information, the rat was more likely to choose
      correctly; when our spike-timing-decoding algorithm extracted misleading texture
      information, the rat was more likely to err. For spike rate information, the
      relationship between faithfulness of the message and correct choice was
      significant but weaker. These results indicate that spike timing makes crucial
      contributions to tactile perception, complementing and surpassing those made by
      rate. The language by which somatosensory cortical neurons transmit information,
      and the readout mechanism used to produce behavior, appears to rely on
      multiplexed signals from spike rate and timing.

PMID- 25619765
TI  - The CENP-A N-tail confers epigenetic stability to centromeres via the CENP-T
      branch of the CCAN in fission yeast.
AB  - In most eukaryotes, centromeres are defined epigenetically by presence of the
      histone H3 variant CENP-A [1-3]. CENP-A-containing chromatin recruits the
      constitutive centromere-associated network (CCAN) of proteins, which in turn
      directs assembly of the outer kinetochore to form microtubule attachments and
      ensure chromosome segregation fidelity [4-6]. Whereas the mechanisms that load
      CENP-A at centromeres are being elucidated, the functions of its divergent N
      terminal tail remain enigmatic [7-12]. Here, we employ the well-studied fission
      yeast centromere [13-16] to investigate the function of the CENP-A (Cnp1) N-tail.
      We show that alteration of the N-tail does not affect Cnp1 loading at
      centromeres, outer kinetochore formation, or spindle checkpoint signaling but
      nevertheless elevates chromosome loss. N-tail mutants exhibited synthetic
      lethality with an altered centromeric DNA sequence, with rare survivors harboring
      chromosomal fusions in which the altered centromere was epigenetically
      inactivated. Elevated centromere inactivation was also observed for N-tail
      mutants with unaltered centromeric DNA sequences. N-tail mutants specifically
      reduced localization of the CCAN proteins Cnp20/CENP-T and Mis6/CENP-I, but not
      Cnp3/CENP-C. Overexpression of Cnp20/CENP-T suppressed defects in an N-tail
      mutant, suggesting a link between reduced CENP-T recruitment and the observed
      centromere inactivation phenotype. Thus, the Cnp1 N-tail promotes epigenetic
      stability of centromeres in fission yeast, at least in part via recruitment of
      the CENP-T branch of the CCAN.

PMID- 25619767
TI  - Olfactory neuromodulation of motion vision circuitry in Drosophila.
AB  - It is well established that perception is largely multisensory; often served by
      modalities such as touch, vision, and hearing that detect stimuli emanating from
      a common point in space; and processed by brain tissue maps that are spatially
      aligned. However, the neural interactions among modalities that share no spatial
      stimulus domain yet are essential for robust perception within noisy environments
      remain uncharacterized. Drosophila melanogaster makes its living navigating food
      odor plumes. Odor acts to increase the strength of gaze-stabilizing optomotor
      reflexes to keep the animal aligned within an invisible plume, facilitating odor
      localization in free flight. Here, we investigate the cellular mechanism for
      cross-modal behavioral interactions. We characterize a wide-field motion
      selective interneuron of the lobula plate that shares anatomical and
      physiological similarities with the "Hx" neuron identified in larger flies.
      Drosophila Hx exhibits cross-modal enhancement of visual responses by paired
      odor, and presynaptic inputs to the lobula plate are required for behavioral odor
      tracking but are not themselves the target of odor modulation, nor is the
      neighboring wide-field "HSE" neuron. Octopaminergic neurons mediating increased
      visual responses upon flight initiation also show odor-evoked calcium modulations
      and form connections with Hx dendrites. Finally, restoring synaptic vesicle
      trafficking within the octopaminergic neurons of animals carrying a null mutation
      for all aminergic signaling is sufficient to restore odor-tracking behavior.
      These results are the first to demonstrate cellular mechanisms underlying visual
      olfactory integration required for odor localization in fruit flies, which may be
      representative of adaptive multisensory interactions across taxa.

PMID- 25619768
TI  - A docking interface in the cyclin Cln2 promotes multi-site phosphorylation of
      substrates and timely cell-cycle entry.
AB  - BACKGROUND: Eukaryotic cell division is driven by cyclin-dependent kinases
      (CDKs). Distinct cyclin-CDK complexes are specialized to drive different cell
      cycle events, though the molecular foundations for these specializations are only
      partly understood. In budding yeast, the decision to begin a new cell cycle is
      regulated by three G1 cyclins (Cln1-Cln3). Recent studies revealed that some CDK
      substrates contain a novel docking motif that is specifically recognized by Cln1
      and Cln2, and not by Cln3 or later S- or M-phase cyclins, but the responsible
      cyclin interface was unknown. RESULTS: Here, to explore the role of this new
      docking mechanism in the cell cycle, we first show that it is conserved in a
      distinct cyclin subtype (Ccn1). Then, we exploit phylogenetic variation to
      identify cyclin mutations that disrupt docking. These mutations disrupt binding
      to multiple substrates as well as the ability to use docking sites to promote
      efficient, multi-site phosphorylation of substrates in vitro. In cells where the
      Cln2 docking function is blocked, we observed reductions in the polarized
      morphogenesis of daughter buds and reduced ability to fully phosphorylate the
      G1/S transcriptional repressor Whi5. Furthermore, disruption of Cln2 docking
      perturbs the coordination between cell size and division, such that the G1/S
      transition is delayed. CONCLUSIONS: The findings point to a novel substrate
      interaction interface on cyclins, with patterns of conservation and divergence
      that relate to functional distinctions among cyclin subtypes. Furthermore, this
      docking function helps ensure full phosphorylation of substrates with multiple
      phosphorylation sites, and this contributes to punctual cell-cycle entry.

PMID- 25619769
TI  - Olfactory proxy detection of dietary antioxidants in Drosophila.
AB  - BACKGROUND: Dietary antioxidants play an important role in preventing oxidative
      stress. Whether animals in search of food or brood sites are able to judge the
      antioxidant content, and if so actively seek out resources with enriched
      antioxidant content, remains unclear. RESULTS: We show here that the vinegar fly
      Drosophila melanogaster detects the presence of hydroxycinnamic acids (HCAs)
      potent dietary antioxidants abundant in fruit-via olfactory cues. Flies are
      unable to smell HCAs directly but are equipped with dedicated olfactory sensory
      neurons detecting yeast-produced ethylphenols that are exclusively derived from
      HCAs. These neurons are housed on the maxillary palps, express the odorant
      receptor Or71a, and are necessary and sufficient for proxy detection of HCAs.
      Activation of these neurons in adult flies induces positive chemotaxis,
      oviposition, and increased feeding. We further demonstrate that fly larvae also
      seek out yeast enriched with HCAs and that larvae use the same ethylphenol cues
      as the adults but rely for detection upon a larval unique odorant receptor
      (Or94b), which is co-expressed with a receptor (Or94a) detecting a general yeast
      volatile. We also show that the ethylphenols act as reliable cues for the
      presence of dietary antioxidants, as these volatiles are produced--upon
      supplementation of HCAs--by a wide range of yeasts known to be consumed by flies.
      CONCLUSIONS: For flies, dietary antioxidants are presumably important to
      counteract acute oxidative stress induced by consumption or by infection by
      entomopathogenic microorganisms. The ethylphenol pathway described here adds
      another layer to the fly's defensive arsenal against toxic microbes.

PMID- 25619770
TI  - Colloidal nanocrystals of orthorhombic Cu2ZnGeS4: phase-controlled synthesis,
      formation mechanism and photocatalytic behavior.
AB  - The orthorhombic polymorph of Cu2ZnGeS4 (CZGS) is a metastable wurtzite-derived
      phase that can only be prepared in the bulk form by extensive heating at high
      temperatures (>=790  degrees C) when using the conventional solid-state reaction
      route. By employing a facile solution-based synthetic strategy, we were able to
      obtain phase-pure orthorhombic CZGS in nanocrystalline form at a much lower
      reaction temperature. Prior to this work, the colloidal synthesis of single-phase
      orthorhombic CZGS on the nanoscale has never been reported. We find that the use
      of an appropriate combination of coordinating solvents and precursors is crucial
      to the sole formation of this metastable phase in solution. A possible formation
      mechanism is proposed on the basis of our experimental results. Because CZGS
      consists of environmentally benign metal components, it is regarded as a
      promising alternative material to the technologically useful yet toxic cadmium
      containing semiconductors. The orthorhombic CZGS nanocrystals display strong
      photon absorption in the visible spectrum and are photocatalytically active in
      dye degradation under visible-light illumination. 

PMID- 25619771
TI  - Apolipoprotein E epsilon4 modulates functional brain connectome in Alzheimer's
      disease.
AB  - The apolipoprotein E (APOE) E4 allele is a well-established genetic risk factor
      for Alzheimer's disease (AD). Recent research has demonstrated an APOE E4
      mediated modulation of intrinsic functional brain networks in cognitively normal
      individuals. However, it remains largely unknown whether and how APOE E4 affects
      the brain's functional network architecture in patients with AD. Using resting
      state functional MRI and graph-theory approaches, we systematically investigated
      the topological organization of whole-brain functional networks in 16 APOE E4
      carriers and 26 matched noncarriers with AD at three levels: global whole-brain,
      intermediate module, and regional node/connection. Neuropsychological analysis
      showed that the APOE E4 carriers performed worse on delayed memory but better on
      a late item generation of a verbal fluency task (associated with executive
      function) than noncarriers. Whole-brain graph analyses revealed that APOE E4
      significantly disrupted whole-brain topological organization as characterized by
      (i) reduced parallel information transformation efficiency; (ii) decreased
      intramodular connectivity within the posterior default mode network (pDMN) and
      intermodular connectivity of the pDMN and executive control network (ECN) with
      other neuroanatomical systems; and (iii) impaired functional hubs and their rich
      club connectivities that primarily involve the pDMN, ECN, and sensorimotor
      systems. Further simulation analysis indicated that these altered connectivity
      profiles of the pDMN and ECN largely accounted for the abnormal global network
      topology. Finally, the changes in network topology exhibited significant
      correlations with the patients' cognitive performances. Together, our findings
      suggest that the APOE genotype modulates large-scale brain networks in AD and
      shed new light on the gene-connectome interaction in this disease.

PMID- 25619772
TI  - Ferrocene-based planar chiral imidazopyridinium salts for catalysis.
AB  - Planar chirality remains an underutilized control element in asymmetric
      catalysis. Factors that have limited its broader application in catalysis include
      poor catalyst performance and difficulties associated with the economical
      production of enantiopure planar chiral compounds. The construction of planar
      chiral azolium salts that incorporate a sterically demanding iron sandwich
      complex is now reported. Applications of this new N-heterocyclic carbene as both
      an organocatalyst and a ligand for transition-metal catalysis demonstrate its
      unprecedented versatility and potential broad utility in asymmetric catalysis. 

PMID- 25619773
TI  - DNA mismatch repair enzymes: genetic defects and autoimmunity.
AB  - DNA mismatch repair (MMR) is one of the several DNA repair pathways conserved
      from bacteria to humans. The primary function of MMR is to eliminate the mismatch
      of base-base insertions and deletions that appear as a consequence of DNA
      polymerase errors at DNA synthesis. The genes encoding the DNA MMR enzymes
      (MMREs) are highly conserved throughout evolution. In humans, there are two sets
      of MMREs, corresponding to homologues of the bacterial MutLS systems. The human
      MutS enzymes consist of MSH2, MSH3 and MSH6, and the human MutL enzymes include
      MLH1, MLH3, PMS1 and PMS2. Since the beginning of this century, a few reports on
      autoantibodies to some MMREs have been reported in autoimmune inflammatory
      myopathy, cancer and hematological disorders. This review charts the functional
      structures of MMREs, their genetic defects and associated disorders, and
      autoimmunity to MMREs, including our recent data that was the first to analyze
      autoantibodies against all seven kinds of MMREs in systemic autoimmune diseases,
      including idiopathic inflammatory myopathies. 

PMID- 25619774
TI  - Novel Nanomonitor ultra-sensitive detection of troponin T.
AB  - BACKGROUND: Troponin is the preferred biomarker for diagnosing myocardial
      infarction. Point of care devices have not matched the sensitivity of laboratory
      based methods for measuring troponin. The Nanomonitor is a novel point-of-care
      device that uses the change in electrical impedance that occurs when a biomarker
      binds to its antibody, which is then correlated to the concentration of the
      target biomarker. METHODS: Performance characteristics of the Nanomonitor were
      evaluated and compared to a standard laboratory-based method. RESULTS: The limit
      of detection of the Nanomonior for troponin T was 0.0088ng/l. Total imprecission
      was 2.38% and 0.85% at troponin T concentrations of 73ng/l and 1800ng/l. The
      functional sensitivity (10% coeffecient of variation) was 0.329ng/l. The linear
      regression had a slope of 0.996 (95% confidence interval, 0.991, 1.002), r=1.00,
      and an intercept of 15.88ng/l (95% confidence interval, -68.39ng/l, 100.15ng/l).
      The mean difference between the assays was -7.54ng/l, determined by Bland-Altman
      analysis. CONCLUSION: The Nanomonitor preliminary results have favorable
      performance characteristics for detecting troponin T in patient blood, provide
      results in 15min, and are portable. More research is needed.

PMID- 25619775
TI  - Guiding protractor for accurate freehand placement of ventricular catheter in
      ventriculoperitoneal shunting.
AB  - BACKGROUND: While frameless stereotaxis can be used for shunt ventricular
      catheter placement in patients with smaller ventricles, the ventricular catheter
      is still commonly placed based on the surface anatomy of the head for patients
      with larger ventricles. Thus, surgical techniques and guides facilitating
      accurate and reliable freehand placement of the ventricular catheter still need
      to be devised. METHODS: With the patient in a supine position and the axis of
      their head maintained horizontally, the guiding protractor is placed horizontally
      in the frontal burrhole at Kocher's point. Using the guiding angle between the
      head axis and the frontal horn of the lateral ventricle based on coronal head
      computed tomography (CT) or magnetic resonance (MR) images, the ventricular
      catheter is then placed in the catheter guide within the guiding protractor.
      RESULTS: In 20 hydrocephalic patients with a bicaudate index >0.2 or bifrontal
      distance >25 mm, the ideal guiding angle ranged from 17 to 23 degrees  (mean +/-
      standard deviation [SD], 19.6 degrees  +/- 1.6 degrees ). In all these patients,
      ventricular catheterization was successfully achieved with only one pass of the
      catheter, and postoperative CT scans showed satisfactory placement of the
      catheter in the ipsilateral frontal horn of the lateral ventricles. CONCLUSIONS:
      The proposed surgical technique using a guiding protractor facilitates accurate
      freehand placement of a ventricular catheter for patients with a bicaudate index
      >0.2 or bifrontal distance >25 mm.

PMID- 25619776
TI  - Quantitative ultrasound measurements at the heel: improvement of short- and mid
      term speed of sound precision.
AB  - Calcaneal quantitative ultrasound can be used to predict osteoporotic fracture
      risk, but its ability to monitor therapy is unclear possibly because of its
      limited precision. We developed a quantitative ultrasound device (foot ultrasound
      scanner) that measures the speed of sound at the heel with the aim of minimizing
      common error sources like the position and penetration angle of the ultrasound
      beam, as well as the soft tissue temperature. To achieve these objectives, we
      used a receiver array, mechanics to adjust the beam direction and a foot
      temperature sensor. In a group of 60 volunteers, short-term precision was
      evaluated for the foot ultrasound scanner and a commercial device (Achilles
      Insight, GE Medical, Fairfield, CT, USA). In a subgroup of 20 subjects, mid-term
      precision (1-mo follow-up) was obtained. Compared with measurement of the speed
      of sound with the Achilles Insight, measurement with the foot ultrasound scanner
      reduced precision errors by half (p < 0.05). The study indicates that improvement
      of the precision of calcaneal quantitative ultrasound measurements is feasible.

PMID- 25619777
TI  - Cancer therapy-induced cardiotoxicity: role of ultrasound deformation imaging as
      an aid to early diagnosis.
AB  - In the last decade, ultrasound deformation imaging, based on both Doppler and
      speckle tracking echocardiography techniques, has emerged as a more sensitive
      tool to identify subtle and subclinical left ventricular systolic dysfunction in
      several clinical settings compared with ejection fraction. In this article, we
      review the evidence relative to the application of ultrasound deformation imaging
      to the oncologic field for detection of left ventricular systolic dysfunction
      induced by cardiotoxic treatments with the aim of verifying whether this approach
      may actually help in early diagnosis of chemotherapy-induced cardiotoxicity.

PMID- 25619779
TI  - Reply regarding Virtual navigation and fusion imaging in percutaneous ablations
      in the neck.

PMID- 25619778
TI  - Non-invasive in vivo characterization of human carotid plaques with acoustic
      radiation force impulse ultrasound: comparison with histology after
      endarterectomy.
AB  - Ischemic stroke from thromboembolic sources is linked to carotid artery
      atherosclerotic disease with a trend toward medical management in asymptomatic
      patients. Extent of disease is currently diagnosed by non-invasive imaging
      techniques that measure luminal stenosis, but it has been suggested that a better
      biomarker for determining risk of future thromboembolic events is plaque
      morphology and composition. Specifically, plaques that are composed of
      mechanically soft lipid/necrotic regions covered by thin fibrous caps are the
      most vulnerable to rupture. An ultrasound technique that non-invasively
      interrogates the mechanical properties of soft tissue, called acoustic radiation
      force impulse (ARFI) imaging, has been developed as a new modality for
      atherosclerotic plaque characterization using phantoms and atherosclerotic pigs,
      but the technique has yet to be validated in vivo in humans. In this preliminary
      study, in vivo ARFI imaging is presented in a case study format for four patients
      undergoing clinically indicated carotid endarterectomy and compared with
      histology. In two type Va plaques, characterized by lipid/necrotic cores covered
      by fibrous caps, mean ARFI displacements in focal regions were high relative to
      the surrounding plaque material, suggesting soft features were covered by stiffer
      layers within the plaques. In two type Vb plaques, characterized by heavy
      calcification, mean ARFI peak displacements were low relative to the surrounding
      plaque and arterial wall, suggesting stiff tissue. This pilot study illustrates
      the feasibility and challenges of transcutaneous ARFI for characterizing the
      material and structural composition of carotid atherosclerotic plaques via
      mechanical properties, in humans, in vivo.

PMID- 25619780
TI  - Phyllodes tumor diagnosed after ultrasound-guided vacuum-assisted excision:
      should it be followed by surgical excision?
AB  - Our aim was to retrospectively evaluate the results of ultrasound (US)-guided
      vacuum-assisted excision (US-VAE) of phyllodes tumors (PTs). A total of 41 PTs
      diagnosed at US-VAE followed by surgery (n = 27) or at least 2 y of US monitoring
      (n = 14) were included. By comparison of US-VAE pathology with surgical histology
      or follow-up US results, cases were divided into upgraded (malignant) and non
      upgraded (benign) groups. These two groups were compared with respect to
      clinical, procedural and US features. Among 27 surgical cases, 2 (8.7%) of 23
      benign PTs were upgraded to malignant PTs. The Breast Imaging Reporting and Data
      System category was retrospectively assigned as 4a (50%) or 4b (50%) in the
      upgraded group (n = 2) and 3 (64%) or 4a (36%) in the non-upgraded group (n = 39)
      (p = 0.018). Residual tumor was observed at the site of US-VAE in 15 of 27
      surgical cases and 0 of 14 US follow-up cases (36.6%, 15/41). Given the rates of
      upgrade to malignancy (8.7%) and residual tumor (36.6%), PTs diagnosed after US
      VAE should be surgically excised.

PMID- 25619782
TI  - Multiple extracorporeal shock wave therapy degrades capsular fibrosis after
      insertion of silicone implants.
AB  - Capsular fibrosis is the most frequent long-term complication after insertion of
      silicone devices. Today, mainly direct immunostimulation and subclinical
      infection are held responsible for inducing and maintaining inflammatory
      reactions, which lead to overwhelming extracellular matrix formation.
      Extracorporeal shock waves (ESWs) are capable of inhibiting inflammatory
      processes and revealing antibacterial capacity. In our previous study, we
      observed decelerated capsule development after application of a single shock wave
      immediately after surgery. The purpose of this study was to evaluate the effects
      of multiple ESWT after insertion of silicone implants in the same rodent model.
      Therefore, silicone prostheses were inserted into a submuscular pocket in 12
      additional male Lewis rats, and shock waves were administered over a 14-d
      interval. At 35 d (n = 6) and 100 d (n = 6) after insertion, silicone implants
      and surrounding capsule tissue were removed and prepared for histologic and
      immunohistochemical analysis, as well as polymerase chain reaction (Ccl2, CD68,
      transforming growth factor beta1, matrix metalloproteinase 2). Compared with the
      control group, multiple ESWT had no effect on day 35, but resulted in a
      significantly thinner capsule on day 100 (825.8 +/- 313.2 vs. 813.3 +/- 47.9, p =
      0.759, and 1062.3 +/- 151.9 vs. 495.4 +/- 220.4, p < 0.001, respectively). The
      capsule was even thinner than after a single shock wave application, which had
      been found to result in thinner capsules at every time point in our previous
      study. This active degradation of the fibrous envelope caused by multiple ESWs
      was accompanied by synergistic alterations in pro- and anti-fibrotic proteins
      (transforming growth factor beta1 and matrix metalloproteinase 2, respectively).
      In conclusion, after insertion of silicone devices, single ESWT is capable of
      decelerating capsule formation in contrast to multiple ESWT, which degrades
      fibrotic tissue. These findings seem to be associated with inhibition of
      inflammation and beneficial effects on pro- and anti-fibrotic proteins.

PMID- 25619781
TI  - Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low
      boiling-point nanoscale phase-change perfluorocarbon agents.
AB  - Many studies have explored phase-change contrast agents (PCCAs) that can be
      vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and
      therapy. However, few investigations have been published on the utility and
      characteristics of PCCAs as contrast agents in vivo. In this study, we examine
      the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare
      data with those for conventional microbubbles with respect to contrast generation
      and circulation properties. To do this, we develop a custom pulse sequence to
      vaporize and image PCCAs using the Verasonics research platform and a clinical
      array transducer. Results indicate that droplets can produce contrast enhancement
      similar to that of microbubbles (7.29 to 18.24 dB over baseline, depending on
      formulation) and can be designed to circulate for as much as 3.3 times longer
      than microbubbles. This study also reports for the first time the ability to
      capture contrast washout kinetics of the target organ as a measure of vascular
      perfusion.

PMID- 25619783
TI  - Contrast-enhanced ultrasound in the diagnosis of patients suspected of having
      active Crohn's disease: meta-analysis.
AB  - This meta-analysis was aimed at assessing the performance of oral/microbubble
      contrast-enhanced ultrasound (CEUS) in the detection of active Crohn's disease
      (CD). A literature search of PubMed, Medline, the China National Knowledge
      Infrastructure and the Cochrane Library was conducted. Published articles that
      evaluated the diagnostic potency of CEUS in CD were included in the study. A
      total of eight articles, which included 428 patients, were finally analyzed.
      Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio
      and area under the curve were calculated to examine the diagnostic accuracy of
      CEUS. The pooled sensitivity and specificity of CEUS for active CD were 93% (95%
      confidence interval: 89%-95%) and 87% (81%-91%), respectively. The summary
      diagnostic odds ratio was 80.35 (30.93-208.73), and the area under the curve was
      0.9633. In conclusion, this meta-analysis pooled results from previous studies to
      evaluate the accuracy of CEUS in the detection of CD. We found that CEUS has high
      accuracy in the detection of active CD using endoscopy/biopsy or clinical index
      as the reference standard. In the future, CEUS may also be widely used in other
      diseases, reducing the necessity for invasive diagnostic procedure. 

PMID- 25619784
TI  - Comparison of 2-D and 3-D estimates of placental volume in early pregnancy.
AB  - Ultrasound estimation of placental volume (PlaV) between 11 and 13 wk has been
      proposed as part of a screening test for small-for-gestational-age babies. A semi
      automated 3-D technique, validated against the gold standard of manual
      delineation, has been found at this stage of gestation to predict small-for
      gestational-age at term. Recently, when used in the third trimester, an estimate
      obtained using a 2-D technique was found to correlate with placental weight at
      delivery. Given its greater simplicity, the 2-D technique might be more useful as
      part of an early screening test. We investigated if the two techniques produced
      similar results when used in the first trimester. The correlation between PlaV
      values calculated by the two different techniques was assessed in 139 first
      trimester placentas. The agreement on PlaV and derived "standardized placental
      volume," a dimensionless index correcting for gestational age, was explored with
      the Mann-Whitney test and Bland-Altman plots. Placentas were categorized into
      five different shape subtypes, and a subgroup analysis was performed. Agreement
      was poor for both PlaV and standardized PlaV (p < 0.001 and p < 0.001), with the
      2-D technique yielding larger estimates for both indices compared with the 3-D
      method. The mean difference in standardized PlaV values between the two methods
      was 0.007 (95% confidence interval: 0.006-0.009). The best agreement was found
      for regular rectangle-shaped placentas (p = 0.438 and p = 0.408). The poor
      correlation between the 2-D and 3-D techniques may result from the heterogeneity
      of placental morphology at this stage of gestation. In early gestation, the
      simpler 2-D estimates of PlaV do not correlate strongly with those obtained with
      the validated 3-D technique.

PMID- 25619785
TI  - Ultrasound modulates skeletal muscle cytokine levels in rats with heart failure.
AB  - Heart failure is a multisystemic disorder that leads to an imbalance between pro-
      and anti-inflammatory cytokines. Therapeutic ultrasound (TU) has been reported to
      modulate the inflammatory process. The aim of this study was to evaluate the
      effect of TU on pro- and anti-inflammatory cytokine levels in soleus muscle and
      plasma of rats with heart failure. Thirty male Wistar rats (230-260 g) were
      submitted to ligation of the left coronary artery or sham surgery. Six weeks
      after surgery, TU was administered directly to the right lower limb. The results
      indicate that TU promotes reduction of pro-inflammatory cytokine levels (tumor
      necrosis factor alpha, interleukin-6) and increases anti-inflammatory cytokine
      levels (interleukin-10) in the soleus muscle of rats with heart failure. This is
      the first study to find that TU can modulate cytokine levels in rats with heart
      failure. Additionally, this is a first report that TU can modulate interleukin-10
      levels in the soleus muscle.

PMID- 25619786
TI  - Virtual navigation and fusion imaging in percutaneous ablations in the neck.

PMID- 25619787
TI  - Effects of extracorporeal shock wave therapy on functional recovery and
      neurotrophin-3 expression in the spinal cord after crushed sciatic nerve injury
      in rats.
AB  - The study described here investigated the effects of extracorporeal shock wave
      therapy (ESWT) on functional recovery and neurotrophin-3 expression in the spinal
      cord after sciatic nerve injury in rats. Forty-five 8-wk-old rats were used and
      randomly divided into three groups: An experimental group, a control group and a
      sham group. The experimental group received ESWT after the nerve-crushing damage.
      The sciatic functional index and Dartfish Software were used to determine the
      effect of sciatic nerve damage on functional changes. A 1-cm length of spinal
      cord encompassing the L4-6 level was removed for Western blot analysis. The
      sciatic functional index significantly changed in both the ESWT and control
      groups after impairment. In the time course evaluation of the ankle angle in the
      toe off, the ESWT group had statistically significant increases from day 21
      onward. There was a significant difference in neurotrophin-3 expression between
      the groups on days 1, 7 and 14 after impairment. Early application of ESWT
      increased the expression of neurotrophin-3 and neurotrophin-3 mRNA, and daily
      therapy facilitated the activity of macrophages and Schwann cells, which affect
      the survival and regeneration of neurons.

PMID- 25619788
TI  - Detecting median nerve strain changes with cyclic compression apparatus: a
      comparison of carpal tunnel syndrome patients and healthy controls.
AB  - The objective of this study was to detect differences in median nerve strain
      between patients with carpal tunnel syndrome and healthy controls using cyclic
      compression apparatus. Twenty-eight patients with idiopathic carpal tunnel
      syndrome and 30 normal patients were examined by ultrasound elastography. Median
      nerve strain, strain ratio of reference coupler and median nerve area and
      perimeter were measured. The areas under receiver operating characteristic curves
      were compared among the parameters. Median nerve strains of the patients were
      significantly smaller than those of the controls (p < 0.001). Strain ratios,
      areas and perimeters were significantly larger in the patients than in the
      controls (p < 0.001). The areas under curves were 0.963, 0.917, 0.759 and 0.706
      for strain, strain ratio, area and perimeter, respectively. The median nerve
      strain had the highest area under the curve. The ultrasonic strain measurements
      of the median nerve provided by the cyclic compression apparatus were superior to
      morphologic assessment in diagnosing carpal tunnel syndrome.

PMID- 25619789
TI  - Real-time tissue elastography for the detection of vulnerable carotid plaques in
      patients undergoing endarterectomy: a pilot study.
AB  - We examined the utility of ultrasonic real-time tissue elastography (RTE) and
      conventional B-mode ultrasound (US) in the detection of vulnerable carotid
      atherosclerotic plaques. This prospective study comprised 19 patients scheduled
      for carotid endarterectomy. Results obtained from pre-operative RTE and B-mode US
      and post-operative pathology were compared. RTE encoded low, average and high
      deformability as blue, green and red, respectively. Tissue hardness was scored on
      a 5-point scale, and relative strains were calculated. The relative strain was
      1.12 +/- 0.14 for fibrous plaques (n = 4), 0.28 +/- 0.07 for atherosclerotic
      plaques (n = 5), 0.47 +/- 0.31 for intraplaque hemorrhage/thrombosis (n = 5) and
      0.98 +/- 1.04 for complex plaques (n = 5). The sensitivity, specificity and
      accuracy of detection of vulnerable plaques were 25%, 100% and 84.2% for B-mode
      US, 50%, 100% and 89.4% for RTE and 62.5%, 100% and 94.7% for the combination.
      Ultrasonic RTE is a potential candidate for a non-invasive and effective approach
      to identify vulnerable atherosclerotic plaques in the carotid artery.

PMID- 25619790
TI  - Ratio of urine and blood urea nitrogen concentration predicts the response of
      tolvaptan in congestive heart failure.
AB  - AIM: This study was conducted to evaluate the performance of the ratio of urine
      and blood urea nitrogen concentration (UUN/BUN) as a new predictive factor for
      the response of an arginine vasopressin receptor 2 antagonist tolvaptan (TLV) in
      decompensated heart failure patients. METHODS: This study enrolled 70
      decompensated heart failure patients who were administered TLV at University of
      Tokyo Hospital. We collected the data of clinical parameters including UUN/BUN
      before administering TLV. Two different outcomes were defined as follows: having
      over 300 mL increase in urine volume on the first day (immediate urine output
      response) and having any decrease in body weight within one week after starting
      TLV treatment (subsequent clinical response). RESULTS: Among the 70 enrolled
      patients, 37 patients (52.9%) showed immediate urine output response; 51 patients
      (72.9%) showed a subsequent clinical response of body weight decrease. Receiver
      operating characteristics (ROC) analysis showed good prediction by UUN/BUN for
      the immediate response (AUC-ROC 0.86 [0.75-0.93]) and a significantly better
      prediction by UUN/BUN for the subsequent clinical response compared with urinary
      osmolality (AUC-ROC 0.78 [0.63-0.88] vs. 0.68 [0.52-0.80], P < 0.05).
      CONCLUSIONS: We demonstrated that a clinical parameter of UUN/BUN can predict the
      response of TLV even when measured before TLV administration. UUN/BUN might
      enable identification of good responders for this new drug.

PMID- 25619791
TI  - HPC-A dose prediction on the optia(r) cell separator based on a benchmark CE2
      collection efficiency: Promoting clinical efficiency, minimizing toxicity, and
      allowing quality control.
AB  - It has been shown that it is possible to predict the CD 34+ hematopoietic
      progenitor cell dose from collection procedures on TerumoBCT COBE Spectra(r) cell
      separator platform using simple variables available at the start of the
      procedure. In this article, we demonstrate that this can be done simply and
      reliably using TerumoBCT Spectra Optia(r) ("Optia") cell separator platform with
      a very close correlation between predicted and actual results (correlation
      coefficient 0.956). This knowledge can be used to optimize apheresis sessions and
      to minimize harmful effects and costs. In addition, we have shown differences in
      collection efficiency between healthy donors and cancer patients undergoing
      autologous donation. Finally, we have shown a small but significant improvement
      in collection efficiency for the Optia platform compared with the COBE Spectra
      platform.

PMID- 25619792
TI  - Annexin-A1 restricts Th17 cells and attenuates the severity of autoimmune
      disease.
AB  - Annexin-A1 (Anx-A1) is an endogenous anti-inflammatory molecule and while
      described as a repressor of innate immune responses, the role of Anx-A1 in
      adaptive immunity, and in particular in T helper (Th) cell responses, remains
      controversial. We have used a T-cell mediated mouse model of retinal autoimmune
      disease to unravel the role of Anx-A1 in the development of autoreactive Th cell
      responses and pathology. RBP1-20-immunized C57BL/6 Anx-A1(-/-) mice exhibit
      significantly enhanced retinal inflammation and pathology as a result of an
      uncontrolled proliferation and activation of Th17 cells. This is associated with
      a limited capacity to induce SOCS3, resulting in un-restricted phosphorylation of
      STAT3. RBP1-20-specific CD4(+) cells from immunized Anx-A1(-/-) animals generated
      high levels of Th17 cells-associated cytokines. Following disease induction,
      daily systemic administration of human recombinant Anx-A1 (hrAnx-A1), during the
      afferent phase of disease, restrained autoreactive CD4(+) cell proliferation,
      reduced expression of pro-inflammatory cytokines IL-17, IFN-gamma and IL-6 and
      attenuated autoimmune retinal inflammatory disease. Furthermore, in man, Anx-A1
      serum levels when measured in active uveitis patient sera were low and associated
      with the detection of IgM and IgG anti-Anx-A1 antibodies when compared to healthy
      individuals. This data supports Anx-A1 as an early and critical regulator of Th17
      cell driven autoimmune diseases such as uveitis. 

PMID- 25619793
TI  - Nonuniform gene expression pattern detected along the longitudinal axis in the
      matured rice leaf.
AB  - Rice (Oryza sativa) is a staple crop that supports half the world's population
      and an important monocot model system. Monocot leaf matures in a basipetal
      manner, and has a well-defined developmental gradient along the longitudinal
      axis. However, little is known about its transcriptional dynamics after leaf
      maturation. In this study, we have reconstructed a high spatial resolution
      transcriptome for the matured rice leaf by sectioning the leaf into seven 3-cm
      fragments. We have performed strand-specific Illumina sequencing to generate gene
      expression profiles for each fragment. We found that the matured leaf contains a
      longitudinal gene expression gradient, with 6.97% (2,603) of the expressed genes
      showing differentially expression along the seven sections. The leaf
      transcriptome showed a gradual transition from accumulating transcripts related
      to primary cell wall and basic cellular metabolism at the base to those involved
      in photosynthesis and energy production in the middle, and catabolic metabolism
      process toward the tip. 

PMID- 25619796
TI  - Conformational and connotational heterogeneity: a surprising relationship between
      protein structural flexibility and puns.
AB  - Protein structures are often thought of as static objects, and indeed, the bulk
      of a protein's sequence forms alpha-helices, beta-sheets, and other generally
      well-ordered substructures. These portions of the molecule pre-pay the entropic
      price of maintaining a globally unique fold, freeing other regions to adopt
      multiple alternative conformations. In many cases, this localized flexibility is
      biologically interesting: it may be important for catalytic turnover or for
      conformational selection before forming an intermolecular complex, for example.
      Similarly, most of written language is carefully tuned to avoid ambiguity and
      convey a singular meaning, a cohesive message. This linguistic scaffolding in
      some sense pre-pays a rhetorical price, paving the way for punctuated instances
      in which a given word or phrase can simultaneously adopt multiple alternative
      connotations-in other words, for puns.

PMID- 25619795
TI  - Is there a limit for the laparoscopic approach of a retroperitoneal residual mass
      postchemotherapy?
AB  - OBJECTIVES: Rescue lymphadenectomy for testicular cancer is a complex surgery,
      with a high number of complications. The laparoscopic approach appears to offer
      faster recovery and improved quality of life compared with open surgery. The aim
      of our study is to report on our experience and to define whether there is a
      limit (oncological, anatomical or technical) for laparoscopic management.
      MATERIAL AND METHODS: A retrospective study was conducted of 15 patients who
      underwent laparoscopic retroperitoneal lymphadenectomy after chemotherapy. In
      addition to epidemiological and oncologic variables, we analyzed the mean
      surgical time, intraoperative and postoperative complications, the mean hospital
      stay and the mean follow-up time. RESULTS: The mean surgical time was 294 minutes
      (range, 180-240). There were 4 large-vessel vascular lesions, all of which were
      large-volume retroperitoneal masses, with diameters >7 cm. The rate of
      postoperative complications was 33%; there was only 1 case of Clavien >III. The
      mean hospital stay was 5.38 days (range, 2-9), and the mean patient follow-up was
      28.9 months (range, 1-79). There was no recurrence in any of the cases.
      CONCLUSIONS: The laparoscopic approach is an oncologically safe option for the
      rescue treatment of testicular cancer. The complex location of these masses
      entails the onset of severe intraoperative complications. We have observed a
      clear relationship between vascular complications and large masses (>7 cm). We
      therefore believe that it would be appropriate to establish a limit on the size
      for laparoscopic treatment.

PMID- 25619794
TI  - The hidden hand of chloride in hypertension.
AB  - Among the environmental factors that affect blood pressure, dietary sodium
      chloride has been studied the most, and there is general consensus that increased
      sodium chloride intake increases blood pressure. There is accruing evidence that
      chloride may have a role in blood pressure regulation which may perhaps be even
      more important than that of Na(+). Though more than 85 % of Na(+) is consumed as
      sodium chloride, there is evidence that Na(+) and Cl(-) concentrations do not go
      necessarily hand in hand since they may originate from different sources. Hence,
      elucidating the role of Cl(-) as an independent player in blood pressure
      regulation will have clinical and public health implications in addition to
      advancing our understanding of electrolyte-mediated blood pressure regulation. In
      this review, we describe the evidence that support an independent role for Cl(-)
      on hypertension and cardiovascular health.

PMID- 25619797
TI  - [Acceptability of human papillomavirus vaccine in mothers from Valencia (Spain)].
AB  - INTRODUCTION: In October 2008, Valencian Community started its human
      papillomavirus (HPV) vaccination schedules for 14 year-old girls. The aim of this
      study is to assess knowledge about HPV infection and its vaccine among the
      mothers of these girls, and to identify factors associated with the willingness
      to vaccinate their daughters. MATERIAL AND METHODS: Cross-sectional study by
      means of a questionnaire to mothers of girls born in 1995, and attending
      secondary schools in the province of Valencia during 2010-2011. Cluster
      stratified random sample (n=1279). STATISTICAL ANALYSIS: percentages, confidence
      intervals, OR, Chi-squared and multivariate logistic regression contrasts.
      RESULTS: A total of 833 (65.1%) questionnaires were completed. The results
      obtained showed that, 76.6% of mothers had vaccinated their daughters against
      HPV; 93.8% knew about the vaccine, particularly through television (71.5%); and
      78.5% received positive advice from a health professional which increased the
      vaccination of their daughters (OR: 2.4). There was low overall knowledge about
      HPV infection and vaccination. Confidence of the mothers in vaccines as a
      preventative method increases the HPV vaccination (OR: 3.8). The first reason for
      refusal was the fear of adverse events (45.6%). CONCLUSIONS: Apparently, the
      media does not influence the willingness to vaccinate. It would be desirable to
      minimize the perception of risk of the vaccine. Positive health advice from a
      health professional can have a positive effect on vaccination. There is a gap
      between the level of knowledge and decision-making to vaccinate.

PMID- 25619799
TI  - Gene expression of ABC transporters in Cooperia oncophora after field and
      laboratory selection with macrocyclic lactones.
AB  - The most widespread helminth parasites of grazing cattle in northern Europe are
      the gastrointestinal nematodes Ostertagia ostertagi and Cooperia oncophora. Heavy
      reliance on the use of macrocyclic lactone (ML) in cattle has led to world-wide
      emergence of resistance to this drug class in C. oncophora. There is evidence
      that members of the ATP-binding cassette (ABC) transporter family, such as P
      glycoproteins (P-gp) and multidrug-resistant proteins (MRP), play a role in
      resistance to ML. In this study gene expression of Con-pgp9, Con-pgp11, Con
      pgp12, Con-pgp16 and Con-mrp1 was examined in two isolates of C. oncophora
      sharing the same genetic background but exposed to ML differently. For isolate
      one (Laboratory-selected), adult worms were recovered before and after treatment
      with ML in vivo. For isolate two (Field-selected), adult worms were collected
      from tracer animals that had never received anthelmintics themselves. One group
      grazed together with untreated animals and one group grazed with animals that
      received suppressive prophylactic treatment with ML at monthly intervals for up
      to two consecutive grazing seasons. Real-time PCR data demonstrated differences
      in gene expression after ML selection, with the highest constitutive expression
      levels for Con-pgp16 and Con-mrp1. Remarkably, the same pattern of increasing
      expression levels of the ABC transport genes was observed in both Laboratory- and
      Field-selected isolates, despite the Field-selected isolate not being directly
      exposed to ML. The higher expression levels of ABC transporters observed in the
      Field-selected isolate was thus not a response to direct exposure to ML, but
      rather appeared to reflect a genetic characteristic inherited from worms in the
      previous generation which had survived exposure to ML in the co-grazing treated
      animals. 

PMID- 25619798
TI  - Ameliorating treatment-refractory depression with intranasal ketamine: potential
      NMDA receptor actions in the pain circuitry representing mental anguish.
AB  - This article reviews the antidepressant actions of ketamine, an N-methyl-D
      aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural
      mechanism for intranasal ketamine's ultra-rapid actions based on the key role of
      NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous
      ketamine infusions can lift mood within hours, the current review describes how
      intranasal ketamine administration can have ultra-rapid antidepressant effects,
      beginning within minutes (5-40 minutes) and lasting hours, but with repeated
      treatments needed for sustained antidepressant actions. Research in rodents
      suggests that increased synaptogenesis in PFC may contribute to the prolonged
      benefit of ketamine administration, beginning hours after administration.
      However, these data cannot explain the relief that occurs within minutes of
      intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of
      intranasal administration in humans may be due to ketamine blocking the NMDAR
      circuits that generate the emotional representations of pain (eg, Brodmann Areas
      24 and 25, insular cortex), cortical areas that can be overactive in depression
      and which sit above the nasal epithelium. In contrast, NMDAR blockade in the
      dorsolateral PFC following systemic administration of ketamine may contribute to
      cognitive deficits. This novel view may help to explain how intravenous ketamine
      can treat the symptoms of depression yet worsen the symptoms of schizophrenia. 

PMID- 25619800
TI  - Conditional removal of selectable markers in Trypanosoma cruzi using a site
      specific recombination tool: proof of concept.
AB  - The scarcity of molecular tools for genetic manipulation is a critical obstacle
      for functional genomics studies on Trypanosoma cruzi. The current study adapted
      an inducible site-specific recombination system based on Dimerizable CRE
      recombinase (DiCRE). Two vectors for stable transfection were created, a first
      one to express inactive portions of DiCRE recombinase, and a second plasmid
      containing the loxP sites to test DiCRE activity. After integrating both
      constructs into the T. cruzi genome, it was shown that DiCRE recombinase can be
      efficiently used to manipulate its genome by allowing the removal of selectable
      markers thus generating homogeneous populations. The DiCRE recombinase success
      allows conditional knockout and the removal of selectable markers without prior
      parasite modification, which also facilitate the transferring of DiCRE
      recombinase to different T. cruzi strains. 

PMID- 25619801
TI  - Validity of the temporal-to-nasal macular ganglion cell-inner plexiform layer
      thickness ratio as a diagnostic parameter in early glaucoma.
AB  - PURPOSE: To evaluate the diagnostic validity of temporal-to-nasal macular
      ganglion cell-inner plexiform layer thickness (TNM) ratio using Cirrus high
      definition-optical coherence tomography (HD-OCT) in patients with early
      glaucomatous damage. METHODS: Enrolled participants included 130 normal controls,
      50 patients with preperimetric glaucoma and 106 patients with early glaucoma. The
      patients with early glaucoma were classified into two subgroups according to the
      pattern of the visual field (VF) defects: the paracentral scotoma (PCS, n = 54)
      and the peripheral scotoma (PPS, n = 52). The thickness of the macular ganglion
      cell-inner plexiform layer (mGCIPL) and circumpapillary retinal nerve fibre layer
      (cpRNFL) was measured by Cirrus HD-OCT, and the average, superior and inferior
      TNM ratio was calculated. The average TNM ratio is a sum of superotemporal and
      inferotemporal mGCIPL thicknesses divided by the sum of superonasal and
      inferonasal mGCIPL thicknesses. Area under the receiver operating characteristic
      curve (AROC) of each parameter was compared between the groups. RESULTS: The
      parameter with the best AROC was the average TNM ratio and inferotemporal mGCIPL
      thickness in the PCS group and average cpRNFL thickness in the PPS group. The
      AROCs of the average, superior and inferior TNM ratio (p < 0.001, p = 0.007 and p
      < 0.001, respectively), minimum, average, inferotemporal and inferior mGCIPL
      thickness (p = 0.004, p = 0.003, p = 0.002 and p = 0.001, respectively) of the
      PCS were significantly higher than those of the PPS. However, the AROCs of the
      all cpRNFL thickness parameters did not show statistically significant
      differences between two subgroups. CONCLUSION: Asymmetry of temporal-to-nasal
      mGCIPL thickness could be an important parameter in the diagnosis of early
      glaucoma with paracentral VF defects.

PMID- 25619802
TI  - Quercetin Induces Antiproliferative Activity Against Human Hepatocellular
      Carcinoma (HepG2) Cells by Suppressing Specificity Protein 1 (Sp1).
AB  - Preclinical Research Quercetin, found in red onions and red apple skin can induce
      apoptosis insome malignant cells. However, the apoptotic effect of quercetin in
      hepatocellular carcinoma HepG2 cells via regulation of specificity protein 1
      (Sp1) has not been studied. Here, we demonstrated that quercetin decreased cell
      growth and induce apoptosis in HepG2 cells via suppression of Sp1 using 3-(4,5
      dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner
      salt (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V, and
      Western blot analysis, an effect that was dose- and time-dependent manner.
      Treatment of HepG2 cells with quercetin reduced cell growth and induced
      apoptosis, followed by regulation of Sp1 and Sp1 regulatory protein. Taken
      together, the results suggest that quercetin can induce apoptotic cell death by
      regulating cell cycle and suppressing antiapoptotic proteins. Therefore,
      quercetin may be useful for cancer prevention. Drug Dev Res 76 : 9-16, 2015.

PMID- 25619803
TI  - Little things matter.

PMID- 25619804
TI  - Bronchopleural fistula after bilateral sequential lobar lung transplantation:
      Technical details of a successful repair.

PMID- 25619805
TI  - Prognostic Value of Molecular Detection of Lymph Node Metastases After Curative
      Resection of Stage II Colon Cancer: A Systematic Pooled Data Analysis.
AB  - BACKGROUND: We aimed to clarify the prognostic value of guanylyl cyclase C (GCC)
      lymph node ratio (LNR) status as a predictor of recurrence in untreated stage IIA
      colon cancer on the basis of pooled individual data from previous studies.
      METHODS: Patients were classified according to predefined GCC LNR risk groups
      (low, LNR <= 0.1; intermediate, 0.1 < LNR <= 0.2; high, LNR > 0.2). Outcomes
      included time to recurrence, disease-free survival, and overall survival.
      Stratified log-rank tests and multivariate Cox models assessed the association
      between outcomes and GCC lymph node status. RESULTS: The final data set contained
      553 patients with stage IIA colon cancer with a median of 18 lymph nodes examined
      after resection; 65 patients (11.8%) had recurrence. Overall, 109 patients
      (19.7%) were classified high risk on the basis of GCC LNR. In multivariate
      analysis, high GCC LNR value (> 0.2) was a significant predictor of cancer
      recurrence (hazard ratio [HR], 3.18; 95% confidence interval [CI], 1.77-5.71; P <
      .001) and lower disease-free survival (HR, 2.40; 95% CI, 1.60-3.62; P < .001) and
      overall survival (HR, 2.12; 95% CI, 1.35-3.33; P = .001). CONCLUSION: Patients
      considered at high risk on the basis of their GCC LNR status have significantly
      inferior outcomes compared to those with low GCC LNR values, particularly among
      those traditionally considered to be at low risk for recurrence.

PMID- 25619806
TI  - Skin intervention of fullerene-integrated nanoemulsion in structural and collagen
      regeneration against skin aging.
AB  - Despite the fact that intrinsic oxidative stress is inevitable, the extrinsic
      factor such as ultraviolet radiation enhances reactive oxygen species (ROS)
      generation resulting in premature skin aging. Nanoemulsion was loaded with
      fullerene, a strong free radical scavenger, and its efficacy to provide
      protection and regenerative effect against ROS-induced collagen breakdown in
      human skin was studied. Stable fullerene nanoemulsions were formulated using high
      shear homogenization and ultrasonic dispersion technique. An open trial was
      conducted using fullerene nanoemulsion on skin twice a day for 28 days. The mean
      collagen score significantly increased (P<0.05) from 36.53+/-4.39 to 48.69+/-5.46
      with 33.29% increment at the end of the treatment. Biophysical characteristics of
      skin revealed that skin hydration was increased significantly (P<0.05) from
      40.91+/-7.01 to 58.55+/-6.08 corneometric units (43.12% increment) and the water
      was able to contain within the stratum corneum without any increased in
      transepidermal water loss. In the in vitro safety evaluation, fullerene
      nanoemulsion showed no acute toxicity on 3T3 fibroblast cell line for 48h and no
      indication of potential dermal irritation. Hence, the fullerene nanoemulsion may
      assist in protecting collagen from breakdown with cosmeceutical benefit. 

PMID- 25619807
TI  - Effect of circulating progesterone concentration during synchronization for fixed
      time artificial insemination on ovulation and fertility in Bos indicus (Nelore)
      beef cows.
AB  - Four experiments were designed to evaluate the effect of different circulating
      progesterone (P4) concentrations during a synchronization of ovulation protocol
      for the timed artificial insemination (TAI) of Bos indicus (Nelore) beef cattle.
      In the first trial, 13 ovariectomized Nelore heifers were randomly allocated into
      one of three groups using new P4 devices (New; 1.0 g P4), previously used P4
      devices for 8 days (Used1x), and previously used P4 devices for 16 days (Used2x),
      in a crossover experimental design. The circulating P4 concentrations during the
      P4 device treatment were lower for Used1x (2.3 +/- 0.1 ng/mL) and Used2x (2.0 +/-
      0.1 ng/mL) than those for New (3.8 +/- 0.2 ng/mL; P = 0.001). In the second
      trial, the ovarian follicular dynamics of 60 anestrous cows were evaluated after
      the cows received the treatments described previously (New [n = 20], Used1x [n =
      20], and Used2x [n = 20]). During the insertion of the P4 device, the cows were
      administered 2.0-mg estradiol benzoate. Eight days later, the P4 device was
      removed, and the cows were administered 0.53-mg sodium cloprostenol, 300 IU eCG,
      and 1-mg estradiol cypionate. There were no differences among the groups during
      the interval from P4 device removal to ovulation (73.7 +/- 2.9 vs. 69.8 +/- 2.4
      vs. 68.4 +/- 2.3 hours) or regarding the ovulation rate (70.0% vs. 80.0% vs.
      85.0%). However, the maximum diameter of the largest follicle was greater (P =
      0.06) in the Used2x (15.3 +/- 0.4 mm) than that of New (13.5 +/- 0.8 mm) and
      Used1x (14.9 +/- 0.5 mm). In experiment 3, 443 anestrous cows were randomly
      assigned into one of the three treatments (New [n = 144] vs. Used1x [n = 167] vs.
      Used2x [n = 132]) and received a TAI 48 hours after the P4 device removal. The
      diameter of the largest follicle during the device removal (10.7 +/- 0.3 vs. 11.2
      +/- 0.2 vs. 11.3 +/- 0.3 mm) and the 30-day pregnancy rates (51.4% vs. 53.9% vs.
      43.2%) did not differ among the experimental groups. In experiment 4, a field
      trial with 593 B indicus (Nelore) cows was conducted to evaluate the pregnancy
      per AI using different levels of P4 in a TAI protocol (New [n = 189] vs. Used1x
      [n = 203] vs. Used2x [n = 201]). The pregnancy per AI was similar between the
      treatment groups (63.5% vs. 57.6% vs. 62.7%). In conclusion, the low circulating
      P4 concentrations that were released from a used P4 device efficiently controlled
      the ovarian follicular growth and exhibited no detrimental effects on the
      pregnancy rates of the B indicus (Nelore) beef cattle. 

PMID- 25619808
TI  - Clinical use of deslorelin implants for the long-term contraception in
      prepubertal bitches: effects on epiphyseal closure, body development, and time to
      puberty.
AB  - Long-acting GnRH agonists have been used both for canine estrus induction and
      prevention. The objective of the study was to investigate the use of a deslorelin
      implant as a long-term and reversible contraceptive in prepubertal bitches with
      special regard to the time of epiphyseal closure. Thirteen healthy, crossbreed,
      medium-sized prepubertal female dogs were used in this study. An implant
      containing 9.4 mg (G1, n = 5) and 4.7 mg (G2, n = 4) deslorelin acetate
      (Suprelorin) or a placebo (sodium chloride 0.9%; G3, n = 4) was inserted
      subcutaneously in the interscapular region. Estrus was monitored once daily by
      physical and sexual behavioral changes. Body development, vaginal cytology, and
      serum progesterone and estradiol 17beta concentration were monitored weekly for
      the first 5 weeks, and then every 3 weeks throughout the treatment period.
      Radiographic examinations were performed monthly to determine the epiphyseal
      closure. Half of the deslorelin-treated bitches (G1: n = 2 and G2: n = 2) came
      into estrus during the 83-week observation period. All animals in the control
      group showed estrus between the 39th and 64th weeks of observation. Time to
      puberty averaged 82.7 +/- 8.9 and 61.9 +/- 9.7 weeks in the deslorelin-treated
      (G1 and G2) and the control bitches, respectively (P < 0.02). Both deslorelin
      implants (9.4 and 4.7 mg) can be used efficiently for the long-term prevention of
      estrus in prepubertal bitches; however, epiphyseal closure is clearly delayed
      which was without any clinical effect in the present study.

PMID- 25619809
TI  - Weber C ankle fractures: a retrospective audit of screw number, size,
      complications, and retrieval rates.
AB  - Tibiofibular transfixation of Weber C injuries using a diastasis screw is the
      current method of fixation. However, controversy remains regarding the screw size
      and number, number of cortices engaged, and the interval to screw removal. The
      present study reviewed the current practice in the Wellington Region. A
      retrospective audit of patients with documented Weber C injuries in the Capital &
      Coast District Health Board from June 2012 to December 2013 was performed. The
      clinical medical records and radiographs were reviewed, and the patient
      demographics, surgeon details, screw number, size, cortices engaged, screw
      removal period, and documented complications were recorded. A total of 36
      operations were documented, of which 27 (75%) cases also required fibula plating.
      Of the 36 cases, 25 (69.44%) used a single diastasis screw, 33 (91.67%) used 4.5
      mm screws, and 18 (50%) engaged 3 cortices. Surgical practice did not vary with
      the experience level. Of the 36 patients, 29 (80.56%) underwent routine screw
      removal at a median of 20 (25th to 75th quartile range 16 to 22) weeks. Also, 9
      (25%) cases of screw fracture occurred, with a median documented interval to
      fracture of 18 (25th to 75th quartile range 15 to 20) weeks. The surgical
      management of Weber C injuries is consistent with current practice. The routine
      removal of diastasis screws by 20 weeks postoperatively was not different from
      the documented interval of screw removal when screw fractures had occurred. The
      timing of screw removal needs to be weighed against the fracture risk, patient
      symptoms, and the risk of secondary procedure complications.

PMID- 25619810
TI  - Distraction arthroplasty with arthroscopic microfracture in a patient with
      rheumatoid arthritis of the ankle joint.
AB  - We treated a 39-year-old female who had experienced destruction of her ankle
      joint owing to rheumatoid arthritis. This relatively young patient wished to
      avoid ankle fusion and joint replacement. Therefore, distraction arthroplasty
      with arthroscopic microfracture was performed to improve her symptoms and
      preserve motion. A microfracture procedure specifically for cartilage defects of
      the tibial plafond and talar dome was performed with the arthroscope, after which
      a hinged external fixator was applied to distract the ankle joint. The ankle
      joint space was enlarged by the external device and joint movement allowed. After
      3 months, removal of the external device and repeat arthroscopy revealed newly
      formed fibrocartilage on the surfaces of both the tibia and the talus. At 2 years
      after the surgery, a radiograph showed that the joint space enlargement of the
      ankle had been maintained. The American Orthopaedic Foot and Ankle Society score
      improved from 37 points preoperatively to 82 points at 2 years postoperatively.
      Our findings suggest that good clinical results can be achieved with distraction
      arthroplasty and arthroscopic microfracture in a relatively young patient with
      rheumatoid arthritis. 

PMID- 25619811
TI  - Safety of achilles detachment and reattachment using a standard midline approach
      to insertional enthesophytes.
AB  - Detachment with reattachment of the Achilles tendon is a common surgery for
      debridement of retrocalcaneal exostosis, bursitis, and other insertional
      pathologic entities. The technique involves a midline skin incision on the
      posterior Achilles to the tendon. The distal Achilles attachment is removed in a
      U-shaped manner, leaving the medial and lateral flares, but exposing the
      posterior spur. This midline approach provides excellent exposure and allows for
      rapid and efficient surgical debridement. The tendon is reapproximated and
      repaired with a suture anchor to facilitate fixation to the posterior calcaneus.
      Some surgeons have expressed concerned that the rupture risk could be increased
      in the postoperative period using this technique. The present study was a
      retrospective medical record review of 98 patients (100 feet) who had undergone a
      midline approach with Achilles reattachment after insertional Achilles
      debridement during a 3-year period. The demographic and comorbidity data were
      collected and analyzed. The outcome measures were postoperative rupture and the
      need for revision surgery. The mean age was 51.9 years, and the patients included
      59 females (60.2%) and 39 males (39.8%). The complications included 4 rupture or
      avulsion revisions (4.0%) and 2 recurrent pain and tendinitis revisions (2.0%).
      The most common repeat repair procedure included hardware removal and a flexor
      hallucis longus transfer or augmentation. Nine patients (9.0%) had wound
      complications, 7 (77.8%) of which necessitated incision and drainage. The midline
      approach with Achilles detachment and reattachment is a safe and effective method
      of surgical treatment of insertional Achilles pathologic entities. The low
      reoperation rate of 4.0% will allow foot and ankle surgeons to safely rely on
      this approach. 

PMID- 25619812
TI  - An examination of anatomic variants and incidental peroneal tendon pathologic
      features: a comprehensive MRI review of asymptomatic lateral ankles.
AB  - Intraoperatively, foot and ankle surgeons will encounter peroneal pathologic
      features in patients with asymptomatic lateral ankles. The purpose of the present
      study was to review the ankle magnetic resonance imaging (MRI) scans of patients
      without a history of ankle trauma or lateral ankle pain to determine which
      anatomic variants correlate with peroneal tendon pathologic features and noted
      pathophysiology. A total of 500 MRI scans were screened, 108 (41.90 +/- 20.42) of
      which met the inclusion criteria. The peroneus brevis tendon was intact in 104
      MRI scans (96.30%), and the peroneus longus tendon was intact in 108 (100.00%).
      The results of the present study have confirmed statistically significant
      correlations between the presence of an os perineum and tendinopathy of the
      peroneus longus [rs(106) = 0.27], undulating peroneal grooves and the severity of
      peroneal brevis tears [rs(106) = 0.32], a boomerang-shaped peroneus brevis tendon
      and increasing tendinopathy of the peroneal tendons [brevis (rs(106) = 0.37;
      longus rs(106) = 0.33], and low-lying muscle bellies and chronic injuries of the
      superior peroneal retinaculum (rphi = 0.19). However, the present study did not
      find evidence to support the presumed correlations between peroneal tendon
      pathologic findings and hypertrophied peroneal tubercles, low-lying muscle
      bellies, or the peroneus quartus muscle. Adding to the published data, the
      present study found a statistically significant correlation between undulating
      peroneal grooves and an increasing prevalence of osteophytes within the peroneal
      groove [rs(106) = 0.32]. MRI findings of anatomic variants or peroneal pathologic
      features might be useful for injury prevention; however, we advise caution from
      using the findings alone to advocate surgical intervention. To definitively
      assess causation, prospective, long-term cohort studies are warranted. 

PMID- 25619813
TI  - The Alfin-like homeodomain finger protein AL5 suppresses multiple negative
      factors to confer abiotic stress tolerance in Arabidopsis.
AB  - Plant homeodomain (PHD) finger proteins affect processes of growth and
      development by changing transcription and reading epigenetic histone
      modifications, but their functions in abiotic stress responses remain largely
      unclear. Here we characterized seven Arabidopsis thaliana Alfin1-like PHD finger
      proteins (ALs) in terms of the responses to abiotic stresses. ALs localized to
      the nucleus and repressed transcription. Except AL6, all the ALs bound to G-rich
      elements. Mutations of the amino acids at positions 34 and 35 in AL6 caused loss
      of ability to bind to G-rich elements. Expression of the AL genes responded
      differentially to osmotic stress, salt, cold and abscisic acid treatments. AL5
      over-expressing plants showed higher tolerance to salt, drought and freezing
      stress than Col-0. Consistently, al5 mutants showed reduced stress tolerance. We
      used ChIP-Seq assays to identify eight direct targets of AL5, and found that AL5
      binds to the promoter regions of these genes. Knockout mutants of five of these
      target genes exhibited varying tolerances to stresses. These results indicate
      that AL5 inhibits multiple signaling pathways to confer stress tolerance. Our
      study sheds light on mechanisms of AL5-mediated signaling in abiotic stress
      responses, and provides tools for improvement of stress tolerance in crop plants.

PMID- 25619814
TI  - Prospects for plasmonic hot spots in single molecule SERS towards the chemical
      imaging of live cells.
AB  - Single molecule surface enhanced Raman scattering (SM-SERS) is a highly local
      effect occurring at sharp edges, interparticle junctions and crevices or other
      geometries with a sharp nanoroughness of plasmonic nanostructures ("hot spots").
      The emission of an individual molecule at SM-SERS conditions depends on the local
      enhancement field of the hot spots, as well as the binding affinity and
      positioning at a hot spot region. In this regard, the stability of near-field
      nano-optics at hot spots is critical, particularly in a biological milieu. In
      this perspective review, we address recent advances in the experimental and
      theoretical approaches for the successful development of SM-SERS. Significant
      progress in the understanding of the interaction between the excitation
      electromagnetic field and the surface plasmon modes at the metallic or
      metallic/dielectric interface of various curvatures are described. New knowledge
      on methodological strategies for positioning the analytes for SM-SERS and Raman
      assisted SERS or the SERS imaging of live cells has been acquired and displayed.
      In the framework of the extensive development of SM-SERS as an advancing
      diagnostic analytical technique, the real-time SERS chemical imaging of
      intracellular compartments and tracing of individual analytes has been achieved.
      In this context, we highlight the tremendous potential of SERS chemical imaging
      as a future prospect in SERS and SM-SERS for the prediction and diagnosis of
      diseases. 

PMID- 25619816
TI  - Predatory journals: when outcome is valued over quality.

PMID- 25619815
TI  - Role of Mast Cells and C-Sensory Fibers in Concanavalin A-Induced Paw Edema in
      Two Rat Strains.
AB  - This study investigated a putative contribution of mast cells and C-sensory
      fibers to differences in the development of inflammatory edema following the
      injection of concanavalin A (Con A) into the hind paws of Dark Agouti (DA) and
      Albino Oxford (AO) rats. The treatment of adult rats with mast cell-depletor
      compound 48/80 and neonatal depletion of C-sensory fibers independently revealed
      that leukocyte composition of the inflamed paws and lymph nodes during local
      inflammatory response to Con A was generally regulated in a similar way in DA and
      AO rat strains. However, in DA and AO rats, the decrease and the increase of Con
      A-induced plasma extravasation were associated with mast cell depletion and
      activation, respectively, whereas neonatal capsaicin treatment activated dermal
      mast cells and potentiated inflammatory plasma extravasation only in adult rats
      of DA strain. Hence, strain differences in the development of the inflammatory
      response to Con A are probably controlled by the differences in the interplay
      between mast cells and C-sensory fibers in DA and AO rats. 

PMID- 25619817
TI  - The health status of the elderly population of Iran in 2012.
AB  - BACKGROUND: With advancing age comes dramatic increase in the incidence of
      chronic diseases, disabilities, and mental problems. This study was conducted to
      epidemiologically describe the health status of the elderly population of Iran.
      MATERIAL AND METHODS: People aged >=60 were selected. Mini-nutritional
      assessment, activity of daily living, geriatric depression scale questionnaires
      were administered. Physical diseases and risk factors were also investigated. For
      the purpose of this study, 1350 elderly individuals were randomly selected.
      RESULTS: The mean age of sample was 69.1+/-7.3 and 65.9% were illiterate. From
      total, 727 (53.8%) had vision problems. The most common problem was cataracts
      with a prevalence of 305 (22.6%) patients who were either suffering from
      cataracts or had undergone a surgery for it. From 634 individuals who used
      dentures, 446 (70.3%) wore the same first denture for over 10 years, without
      being examined. 524 (38.8%) of our seniors spent their free time alone at home.
      13.2% of women and 12.6% of men were dependent on others for at least one daily
      activity. In terms of nutrition, 70 (5.5%) of the elderly (46 women and 24 men)
      were severely malnourished with 554 (41.3%) (243 men and 311 women) at risk of
      malnutrition. CONCLUSION: The health status of the elderly in Iran was similar to
      other countries in the world. However there continues to be room for improvement.
      Taking into account the rapidly aging population of Iran, health providers, and
      policy makers are required to take steps at a national level and direct more
      resources into supporting the elderly population.

PMID- 25619818
TI  - Effects of fish community on occurrences of Yangtze finless porpoise in
      confluence of the Yangtze and Wanhe Rivers.
AB  - The Yangtze finless porpoise is a subspecies of narrow-ridged finless porpoise
      endemic to the middle and lower reaches of the Yangtze River and the adjoining
      Poyang and Dongting Lakes. With the depletion of fish stocks in the Yangtze River
      in recent decades, food availability has become the most important factor
      affecting the survival of this subspecies. Despite this, the relationships
      between fish community and occurrences of porpoise are far from being fully
      understood. Therefore, during September 2013 to August 2014, the occurrences of
      porpoise were investigated in confluence of the Yangtze and Wanhe Rivers; fish
      community was also surveyed synchronously in confluence and two adjacent
      transects. The results showed that (1) the confluence had maximum fish species
      richness, and the main dominant species was upper fish, while the other two
      transects were mainly dominated by demersal fish. ANOVA analyses showed that
      individual number and yield of upper fish which can be eaten by porpoise (upper
      edible fish) in the confluence were significantly higher than other two
      transects. (2) Average group size of the porpoise was 3.7 +/- 1.8 individuals.
      The occurrences of porpoise in different seasons had great differences, and the
      porpoise was more likely to be detected in autumn and winter. (3) Fish community
      had significant effects on occurrences of porpoise, and the main influencing
      factors were fish species richness, individual number, and yield of edible fish,
      especially the upper edible fish. The results of this study will have important
      implications for the conservation of porpoise.

PMID- 25619819
TI  - Broad hexagonal columnar mesophases formation in bioinspired transition-metal
      complexes of simple fatty acid meta-octaester derivatives of meso-tetraphenyl
      porphyrins.
AB  - A series of meta-substituted fatty acid octaester derivatives and their
      transition-metal complexes of meso- tetraphenyl porphyrins (TPP-8OOCR, with R =
      C(n-1)H(2n-1), n = 8, 12, or 16) have been prepared through very simple synthesis
      protocols. The thermotropic phase behavior and the liquid crystalline (LC)
      organization structures of the synthesized porphyrin derivatives were
      systematically investigated by a combination of differential scanning calorimetry
      (DSC), polarized optical microscopy (POM), and variable-temperature small-angle X
      ray scattering/wide-angle X-ray scattering (SAXS/WAXS) techniques. The shorter
      octanoic acid ester substituted porphyrin (C8-TPP) did not show liquid
      crystallinity and its metal porphyrins exhibited an uncommon columnar mesophase.
      The lauric acid octaester (C12-TPP) and the palmitic acid octaester (C16-TPP)
      series porphyrins generated hexagonal columnar mesophase Colh. Moreover, the
      metal porphyrins C12-TPPM and C16-TPPM with M = Zn, Cu, or Ni, exhibited well
      organized Colh mesophases of broad LC temperature ranges increasing in the order
      of TPPNi<TPPCu<=TPPZn with their increased effective ionic radii in the square
      planar coordination. The simplicity in synthesis, the well intercolumnar
      organization of Colh mesophase, the broadness of the discotic LC range, and the
      specific UV/Vis absorption and fluorescence emission behaviors make the
      symmetrically substituted fatty acid octaester porphyrins and their metal
      complexes very attractive for variant applications.

PMID- 25619820
TI  - A review of key challenges of electrospun scaffolds for tissue-engineering
      applications.
AB  - Tissue engineering holds great promise to develop functional constructs
      resembling the structural organization of native tissues to improve or replace
      biological functions, with the ultimate goal of avoiding organ transplantation.
      In tissue engineering, cells are often seeded into artificial structures capable
      of supporting three-dimensional (3D) tissue formation. An optimal scaffold for
      tissue-engineering applications should mimic the mechanical and functional
      properties of the extracellular matrix (ECM) of those tissues to be regenerated.
      Amongst the various scaffolding techniques, electrospinning is an outstanding one
      which is capable of producing non-woven fibrous structures with dimensional
      constituents similar to those of ECM fibres. In recent years, electrospinning has
      gained widespread interest as a potential tissue-engineering scaffolding
      technique and has been discussed in detail in many studies. So why this review?
      Apart from their clear advantages and extensive use, electrospun scaffolds
      encounter some practical limitations, such as scarce cell infiltration and
      inadequate mechanical strength for load-bearing applications. A number of
      solutions have been offered by different research groups to overcome the above
      mentioned limitations. In this review, we provide an overview of the limitations
      of electrospinning as a tissue-engineered scaffolding technique, with emphasis on
      possible resolutions of those issues. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25619821
TI  - Initial empirical treatment based on clinical feature of chronic cough.
AB  - BACKGROUND: An empirical therapy based on the clinical characteristics of cough
      had not been reported. We evaluated this strategy of empirical therapy on chronic
      cough. METHODS: Patients with chronic cough were initially diagnosed with
      corticosteroid-responsive cough (CRC), postnasal drip syndrome (PNDS) and
      gastroesophageal reflux-related cough (GERC) based on their medical history and
      clinical presentation, and received a sequential three-step empirical therapy. A
      successful response was required for final diagnosis. RESULTS: A total of 96
      patients were recruited with a median duration of cough for 4 months (range, 2
      100). The primary diagnosis based on history and clinical presentation was CRC in
      53 patients (55.2%), PNDS in 36 (37.5%) and GERC in 7 (7.3%). Cough improved in
      60 patients (62.5%) at the first step with mean time of 6.2 +/- 3.3 days. Three
      step empirical therapy was beneficial in 78 of 96 (81.2%) patients at last. The
      final spectrum and frequency of causes of cough based on therapeutic response
      were as follows: CRC (46.7%), PNDS (27.5%) and GERC (10.8%). Eighteen cases
      (18.8%) were not responsive to empirical treatment, seven of whom were identified
      as other causes by diagnostic tests. CONCLUSIONS: The empirical therapy aimed at
      primary diagnosis on the basis of history and clinical characteristics is a more
      targeted approach, and leads to improvement of chronic cough more quickly in most
      patients. CRC is the most common cause of chronic cough.

PMID- 25619822
TI  - Synthesis and biological evaluation of ferrocenylquinoline as a potential
      antileishmanial agent.
AB  - The emergence of resistance against antileishmanial drugs in current use
      necessitates the search for new classes of antileishmanial compounds. Herein we
      report the design, synthesis, and evaluation of a novel ferrocenylquinoline for
      activity against Leishmania donovani. 7-Chloro-N-[2-(1H-5-ferrocenyl-1,2,3
      triazol-1-yl)ethyl]quinolin-4-amine (1) was generated by coupling an iron(II)
      ethynylferrocene species with 4-(2-ethylazido)amino-7-chloroquinoline using click
      chemistry. The synthesized compound 1 was tested for its antileishmanial activity
      using both promastigote and amastigote stages of L. donovani. Compound 1 showed
      promising anti-promastigote activity, with an IC50 value of 15.26 MUM and no
      cytotoxicity toward host splenocytes. From the battery of tests conducted in this
      study, it appears that this compound induces parasite death by promoting
      oxidative stress and depolarizing the mitochondrial membrane potential, thereby
      triggering apoptosis. These results suggest that ferrocenylquinoline 1 is a
      suitable lead for the development of new antileishmanial drugs. 

PMID- 25619823
TI  - Application of the unified singlet and triplet electron-pair extrapolation scheme
      with basis set rehierarchization to tensorial properties.
AB  - A method previously suggested to calculate the correlation energy at the complete
      one-electron basis set limit by reassigning the basis hierarchical numbers and
      using the unified singlet- and triplet-pair extrapolation scheme is here utilized
      to extrapolate tensorial properties, with specific use for the polarizabilities
      of eight molecules whose raw values are obtained with second-order Moller-Plesset
      perturbation theory and coupled-cluster singles and doubles excitation methods,
      both without and with inclusion of the perturbative triples correction. Good
      agreement is obtained with the best available estimates even when the (d, t) pair
      of hierarchical numbers is utilized to perform the extrapolations. This
      conceivably reinforces our previous finding that there is no good reason to
      exclude double-zeta results in extrapolations, especially if the basis is
      calibrated to comply with the theoretical model. 

PMID- 25619824
TI  - Evolutionary Divergence of Plant Borate Exporters and Critical Amino Acid
      Residues for the Polar Localization and Boron-Dependent Vacuolar Sorting of
      AtBOR1.
AB  - Boron (B) is an essential micronutrient for plants but is toxic when accumulated
      in excess. The plant BOR family encodes plasma membrane-localized borate
      exporters (BORs) that control translocation and homeostasis of B under a wide
      range of conditions. In this study, we examined the evolutionary divergence of
      BORs among terrestrial plants and showed that the lycophyte Selaginella
      moellendorffii and angiosperms have evolved two types of BOR (clades I and II).
      Clade I includes AtBOR1 and homologs previously shown to be involved in efficient
      transport of B under conditions of limited B availability. AtBOR1 shows polar
      localization in the plasma membrane and high-B-induced vacuolar sorting,
      important features for efficient B transport under low-B conditions, and rapid
      down-regulation to avoid B toxicity. Clade II includes AtBOR4 and barley Bot1
      involved in B exclusion for high-B tolerance. We showed, using yeast
      complementation and B transport assays, that three genes in S. moellendorffii,
      SmBOR1 in clade I and SmBOR3 and SmBOR4 in clade II, encode functional BORs.
      Furthermore, amino acid sequence alignments identified an acidic di-leucine motif
      unique in clade I BORs. Mutational analysis of AtBOR1 revealed that the acidic di
      leucine motif is required for the polarity and high-B-induced vacuolar sorting of
      AtBOR1. Our data clearly indicated that the common ancestor of vascular plants
      had already acquired two types of BOR for low- and high-B tolerance, and that the
      BOR family evolved to establish B tolerance in each lineage by adapting to their
      environments. 

PMID- 25619825
TI  - Determination of thermodynamic pKa values of pharmaceuticals from five different
      groups using capillary electrophoresis.
AB  - A determination of the thermodynamic acid dissociation constants (pKa) of 22
      frequently used pharmaceuticals using capillary electrophoresis in aqueous media
      is presented in this work. The investigated pharmaceuticals belong to different
      pharmacological groups: macrolides, fluoroquinolones, sulfonamides, beta-lactams,
      tetracyclines, and other miscellaneous pharmaceuticals. The electrophoretic
      mobilities of the investigated analytes were monitored in a pH range from 2.00 to
      10.82. The data were fitted with an appropriate mathematical model using a
      nonlinear regression analysis to obtain pKa values. Experimentally obtained data
      were well described by the mathematical model chosen for each analyte that was
      confirmed by r(2) values higher than 0.99 for most of the investigated analytes.
      Extrapolations to zero ionic strength were used to determine the thermodynamic
      pKa values. Experimentally obtained acid dissociation constants were interpreted
      using structural formulae of investigated analytes and the moieties corresponding
      to specific pKa were identified.

PMID- 25619826
TI  - Reactive short-chain leaf volatiles act as powerful inducers of abiotic stress
      related gene expression.
AB  - Abiotic stresses cause serious damage to plants; therefore, plants undergo a
      complicated stress response through signal transduction originating from
      environmental stimuli. Here we show that a subset of short-chain leaf volatiles
      with an alpha, beta-unsaturated carbonyl bond in their structure (reactive short
      chain leaf volatiles, RSLVs) like (E)-2-hexenal and (E)-2-butenal can act as
      signal chemicals that strongly induce the gene expression of abiotic-related
      transcription factors, such as heat stress-related transcription factors (HSFA2,
      MBF1c) and other abiotic stress-related transcription factors (DREB2A, ZATs).
      RSLV-induced expression of HSFA2 and MBF1c was eliminated in HSFA1s-, known as
      heat stress response master regulators, knockout mutant, whereas those of DREB2A
      and ZATs were not, suggesting that the RSLV signaling pathway is composed of
      HSFA1-dependent and -independent pathways. RSLV treatment induced production of
      chaperon proteins, and the RSLV-treated Arabidopsis thus demonstrated enhanced
      abiotic stress tolerance. Because oxidative stress treatment enhanced RSLV
      production, we concluded that commonly found RSLVs produced by environmental
      stresses are powerful inducer of abiotic stress-related gene expression as
      oxidative stress signals. 

PMID- 25619827
TI  - Molecular analysis of Dirofilaria repens removed from a subcutaneous nodule in a
      Japanese woman after a tour to Europe.
AB  - A premature female Dirofilaria species, subsequently identified as Dirofilaria
      repens by its morphological features and mitochondrial 12S ribosomal RNA (12S
      rRNA) gene sequence, was removed from a subcutaneous nodule of the right temporal
      region of the head in a Japanese woman 2 years after she noticed swelling of her
      left calf following an insect sting during a tour to Europe; headache symptoms
      were noticed a few months later. The sequences of the mitochondrial 12S rRNA and
      cytochrome c oxidase subunit I genes from the organism were almost identical to
      those of sequences AM779772 (100% homology, 337/337) and AM749233 (99.8%
      homology, 536/537) of D. repens isolated from humans in Italy. However, the
      phylogenetic position of the 18S rRNA-internal transcribed spacer 1-5.8S rRNA
      region was in the same cluster as that of sequence JX290195 of Dirofilaria sp.
      "hongkongensis" (96.7% homology, 348/360), which was recently reported from Hong
      Kong as a novel Dirofilaria species. Information on regional genetic variation in
      D. repens isolated from animals and humans remains scarce. We report the detailed
      genetic features of this filaria as a reference isolate from a specific endemic
      area, to enrich the genetic database of D. repens.

PMID- 25619828
TI  - IFNg-induced Irgm1 promotes tumorigenesis of melanoma via dual regulation of
      apoptosis and Bif-1-dependent autophagy.
AB  - Interferon gamma (IFNg) has been known as the regulator for both tumor immune
      surveillance and tumorgenesis. However, mechanisms underlying the resistance of
      tumor cell to IFNg have yet been fully understood. In the current study, we
      showed that immunity-related GTPase family member 1 (mouse: Irgm1; human: IRGM)
      is essential for IFNg-mediated regulation of tumor cell growth in melanoma.
      IRGM/Irgm1 was highly expressed in human and mouse melanoma. IFNg and starvation
      synergistically induced Irgm1 expression in melanoma B16 cells. In vivo,
      injection of Irgm1-siRNA-treated cells significantly reduced the number of tumor
      nodules and prolonged the mice survival. In vitro, knockdown endogenous or IFNg
      induced Irgm1 significantly decreases the proliferation and increases apoptosis
      of B16 cells. In addition, suppressing Irgm1 decreased the IFNg/starvation
      induced autophagy, while overexpressing Irgm1 significantly increased autophagy
      and rescued starvation-challenged cells. Moreover, IFNg and starvation-induced
      the co-localization of Irgm1 with Bax-interacting factor 1 (Bif-1). Knockdown of
      Bif-1 decreased Irgm1-mediated tumor cell autophagy. Taken together, these data
      reveal an Irgm1-dependent mechanism that promotes the tumorigenesis of melanoma
      via dual regulation of apoptosis and Bif-1-dependent autophagy. 

PMID- 25619829
TI  - A novel recurrent CHEK2 Y390C mutation identified in high-risk Chinese breast
      cancer patients impairs its activity and is associated with increased breast
      cancer risk.
AB  - Certain predisposition factors such as BRCA1/2 and CHEK2 mutations cause familial
      breast cancers that occur early. In China, breast cancers are diagnosed at
      relatively younger age, and higher percentage of patients are diagnosed before 40
      years, than that in Caucasians. However, the prevalence for BRCA1/2 mutations and
      reported CHEK2 germline mutations is much lower or absent in Chinese population,
      arguing for the need to study other novel risk alleles among Chinese breast
      cancer patients. In this study, we searched for CHEK2 mutations in young, high
      risk breast cancer patients in China and detected a missense variant Y390C (1169A
      > G) in 12 of 150 patients (8.0%) and 2 in 250 healthy controls (0.8%, P =
      0.0002). Four of the Y390C carriers have family history of breast and/or ovarian
      cancer. In patients without family history, Y390C carriers tend to develop breast
      cancer early, before 35 years of age. The codon change at Y390, a highly
      conserved residue located in CHEK2's kinase domain, appeared to significantly
      impair CHEK2 activity. Functional analysis suggested that the CHEK2 Y390C
      mutation is deleterious as judged by the mutant protein's inability to inactivate
      CDC25A or to activate p53 after DNA damage. Cells expressing the CHEK2 Y390C
      variant showed impaired p21 and Puma expression after DNA damage, and the
      deregulated cell cycle checkpoint and apoptotic response may help conserve
      mutations and therefore contribute to tumorigeneisis. Taken together, our results
      not only identified a novel CHEK2 allele that is associated with cancer families
      and confers increased breast cancer risk, but also showed that this allele
      significantly impairs CHEK2 function during DNA damage response. Our results
      provide further insight on how the function of such an important cancer gene may
      be impaired by existing mutations to facilitate tumorigenesis. It also offers a
      new subject for breast cancer monitoring, prevention and management.

PMID- 25619830
TI  - Mast cells induce epithelial-to-mesenchymal transition and stem cell features in
      human thyroid cancer cells through an IL-8-Akt-Slug pathway.
AB  - There is increasing evidence that mast cells (MCs) and their mediators are
      involved in the remodeling of the tumor microenvironment and promote tumor
      growth, angiogenesis and metastasis. We have found that an increased density of
      MCs in thyroid cancer (TC) correlates with enhanced invasiveness. However, the MC
      derived factors responsible for this activity and the mechanisms by which they
      enhance TC invasiveness remain unidentified. Here, we report that MCs, when
      activated by TC cells, produce soluble factors that induce epithelial-to
      mesenchymal transition (EMT) and stemness features of TC cells. We identified
      CXCL8/interleukin (IL)-8 as the main mediator contained in activated MC
      conditioned media (CM) capable of inducing both EMT and stemness of TC cells.
      Mechanistically, MC CM or exogenous IL-8 stimulated Akt phosphorylation and Slug
      expression in TC cells. The inhibition of the Akt pathway or depletion of the
      Slug transcription factor by RNA interference, reverted EMT and stemness
      responses. TC cells stably transfected with exogenous IL-8 underwent EMT,
      displayed increased stemness and enhanced tumorigenicity with respect to control
      cells. The analysis of TC surgical specimens by immunohistochemical analysis
      demonstrated a positive correlation between MC density (Tryptase(+) cells) and
      stemness features (OCT4 staining). Taken together, our data identify an MC
      dependent IL-8-Akt-Slug pathway that sustains EMT/stemness of TC cells. The
      blockade of this circuit might be exploited for the therapy of advanced TC.

PMID- 25619831
TI  - The P2X7 receptor is a key modulator of the PI3K/GSK3beta/VEGF signaling network:
      evidence in experimental neuroblastoma.
AB  - Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of
      cancer-related deaths in childhood, lacking an effective treatment in its
      advanced stages. The P2X7 receptor for extracellular ATP was associated to NB
      cell proliferation and recently emerged as a promoter of tumor engraftment,
      growth and vascularization. In an effort to identify new therapeutic options for
      neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first
      analyzed the effect of P2X7 activation or down-modulation of the main biochemical
      ways involved in NB progression: the PI3K/Akt/GSK3beta/MYCN and the
      HIF1alpha/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced
      PI3K/Akt, while decreasing GSK3beta activity. In the same model, P2X7 silencing
      or antagonist administration reduced the activity of PI3K/Akt and increased that
      of GSK3beta, leading to a decrease in cellular glycogen stores. Similarly, P2X7
      downmodulation caused a reduction in HIF1alpha levels and vascular endothelial
      growth factor (VEGF) secretion. Systemic administration of two different P2X7
      antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor
      growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic
      immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice.
      Together with tumor regression, treatment with P2X7 antagonists caused
      downmodulation of the Akt/HIF1alpha axis, leading to reduced VEGF content and
      decreased vessel formation. Interestingly, in both experimental models, P2X7
      antagonists strongly reduced the expression of the probably best-accepted
      oncogene in NB: MYCN. Finally, we associated P2X7 overexpression with poor
      prognosis in advanced-stage NB patients. Taken together, our data suggest that
      P2X7 receptor is an upstream regulator of the main signaling pathways involved in
      NB growth, metabolic activity and angiogenesis, and a promising therapeutic
      target for neuroblastoma treatment. 

PMID- 25619832
TI  - Cell death by autophagy: emerging molecular mechanisms and implications for
      cancer therapy.
AB  - Autophagy is a tightly-regulated catabolic process of cellular self-digestion by
      which cellular components are targeted to lysosomes for their degradation. Key
      functions of autophagy are to provide energy and metabolic precursors under
      conditions of starvation and to alleviate stress by removal of damaged proteins
      and organelles, which are deleterious for cell survival. Therefore, autophagy
      appears to serve as a pro-survival stress response in most settings. However, the
      role of autophagy in modulating cell death is highly dependent on the cellular
      context and its extent. There is an increasing evidence for cell death by
      autophagy, in particular in developmental cell death in lower organisms and in
      autophagic cancer cell death induced by novel cancer drugs. The death-promoting
      and -executing mechanisms involved in the different paradigms of autophagic cell
      death (ACD) are very diverse and complex, but a draft scenario of the key
      molecular targets involved in ACD is beginning to emerge. This review provides an
      up-to-date and comprehensive report on the molecular mechanisms of drug-induced
      autophagy-dependent cell death and highlights recent key findings in this
      exciting field of research. 

PMID- 25619833
TI  - CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and
      angiogenesis.
AB  - In the present study, we have assessed whether a putative calcium channel
      alpha2delta2 auxiliary subunit (CACNA2D2 gene) could be involved in prostate
      cancer (PCA) progression. We therefore carried out experiments to determine
      whether this protein is expressed in PCA LNCaP cells and in PCA tissues, and
      whether its expression may be altered during cancer development. In addition, we
      evaluated the influence on cell proliferation of overexpressing or downregulating
      this subunit. In vitro experiments show that alpha2delta2 subunit overexpression
      is associated with increased cell proliferation, alterations of calcium
      homeostasis and the recruitment of a nuclear factor of activated T-cells pathway.
      Furthermore, we carried out in vivo experiments on immuno-deficient nude mice in
      order to evaluate the tumorigenic potency of the alpha2delta2 subunit. We show
      that alpha2delta2-overexpressing PCA LNCaP cells are more tumorigenic than
      control LNCaP cells when injected into nude mice. In addition, gabapentin, a
      ligand of alpha2delta2, reduces tumor development in LNCaP xenografts. Finally,
      we show that the action of alpha2delta2 on tumor development occurs not only
      through a stimulation of proliferation, but also through a stimulation of
      angiogenesis, via an increased secretion of vascular endothelial growth factor in
      cells overexpressing alpha2delta2. 

PMID- 25619834
TI  - KLHL39 suppresses colon cancer metastasis by blocking KLHL20-mediated PML and
      DAPK ubiquitination.
AB  - Cullin 3 (Cul3)-family ubiquitin ligases use the BTB-domain-containing proteins
      for the recruitment of substrates, but the regulation of this family of ubiquitin
      ligases has not been completely understood. KLHL20 is a BTB-family protein and
      targets tumor suppressor promyelocytic leukemia protein (PML) and death
      associated protein kinase (DAPK) to its kelch-repeat domain for ubiquitination
      and degradation. Here, we show that another BTB-kelch protein KLHL39 is recruited
      to the substrate-binding domain of KLHL20 but is not a substrate of Cul3-KLHL20
      complex. Interestingly, KLHL39 does not bind Cul3 because of the absence of
      certain conserved residues in the BTB domain. Instead, KLHL39 blocks KLHL20
      mediated ubiquitination of PML and DAPK by disrupting the binding of these
      substrates to KLHL20 as well as the binding of KLHL20 to Cul3. Through the two
      mechanisms, KLHL39 increases the stability of PML and DAPK. In human colon
      cancers, downregulations of KLHL39, PML and DAPK are associated with metastatic
      progression. Furthermore, preclinical data indicate that KLHL39 promotes colon
      cancer migration, invasion and survival in vitro and metastasis in vivo through a
      PML- and DAPK-dependent mechanism. Our study identifies KLHL39 as a negative
      regulator of Cul3-KLHL20 ubiquitin ligase and reveals a role of KLHL39-mediated
      PML and DAPK stabilization in colon cancer metastasis.

PMID- 25619835
TI  - Understanding the Polo Kinase machine.
AB  - The Polo Kinase is a central regulator of cell division required for several
      events of mitosis and cytokinesis. In addition to a kinase domain (KD), Polo-like
      kinases (Plks) comprise a Polo-Box domain (PBD), which mediates protein
      interactions with targets and regulators of Plks. In all organisms that contain
      Plks, one Plk family member fulfills several essential functions in the
      regulation of cell division, and here we refer to this conserved protein as Polo
      Kinase (Plk1 in humans). The PBD and the KD are capable of both cooperation and
      mutual inhibition in their functions. Crystal structures of the PBD, the KD and,
      recently, a PBD-KD complex have helped understanding the inner workings of the
      Polo Kinase. In parallel, an impressive array of molecular mechanisms has been
      found to mediate the regulation of the protein. Moreover, the targeting of Polo
      Kinase in the development of anti-cancer drugs has yielded several molecules with
      which to chemically modulate Polo Kinase to study its biological functions. Here
      we review our current understanding of the protein function and regulation of
      Polo Kinase as a fascinating molecular device in control of cell division. 

PMID- 25619837
TI  - A stress-induced early innate response causes multidrug tolerance in melanoma.
AB  - Correction to: Oncogene (2015) 34, 4448-4459; doi:10.1038/onc.2014.372; published
      online 24 November 2014. In this article, published online 24 November 2014, the
      authors have noticed that the latest supplementary information was not used. The
      corrected supplementary information (Supplementary Materials) appears online
      together with this corrigendum. The authors would like to apologise for any
      inconvenience this may cause

PMID- 25619836
TI  - Three-dimensional microenvironment confers enhanced sensitivity to doxorubicin by
      reducing p53-dependent induction of autophagy.
AB  - Preclinical studies of anticancer drugs are typically performed using cancer cell
      lines maintained in two-dimensional (2D) cultures, ignoring the influences of the
      extracellular matrix (ECM) and three-dimensional (3D) microenvironment. In this
      study, we evaluated the microenvironmental control of human breast cancer cells
      responses to doxorubicin (DOXO) using the 3D laminin-rich ECM (3D lrECM) cell
      culture model. Under 3D culture conditions, MCF-7 cells displayed drastic
      morphological alterations, a decrease in proliferation and elevated sensitivity
      to DOXO. Interestingly, the chemotherapy-mediated activation of autophagy was
      compromised in the 3D matrix, suggesting an association between the increased
      cytotoxicity of DOXO and hindered autophagy induction. Indeed, while chloroquine
      or ATG5 knockdown potentiated DOXO-induced cell death under the 2D culture
      conditions, the autophagy inducer rapamycin improved the resistance of 3D
      cultured cells to this drug. Moreover, in the monolayer-cultured cells, DOXO
      treatment led to increases in p53 and DRAM-1 expression, which is a p53-dependent
      activator of autophagy that functions in response to DNA damage. Conversely, p53
      and DRAM-1 expression was impaired in 3D-cultured cells. The knockdown of p53 by
      shRNA blocked DRAM-1 activation, impaired autophagy induction and sensitized only
      those cells maintained under 2D conditions to DOXO. In addition, 2D-cultured MDA
      MB-231 cells (a p53-mutated breast cancer cell line) not only showed increased
      sensitivity to DOXO compared with MCF-7 cells but also failed to induce DRAM-1
      expression or autophagy. Similar to p53 silencing, DRAM-1 knockdown potentiated
      DOXO cytotoxicity only in 2D-cultured cells. These results suggest that the 3D
      tissue microenvironment controls tumor cell sensitivity to DOXO treatment by
      preventing p53-DRAM-autophagy axis activation. 

PMID- 25619838
TI  - SHP-1 is a negative regulator of epithelial-mesenchymal transition in
      hepatocellular carcinoma.
AB  - Epithelial-to-mesenchymal transition (EMT) is well known to involve in tumor
      invasion and metastasis. Src homology region 2 domain-containing phosphatase 1
      (SHP-1) functions as a potent tumor suppressor and also acts as a negative
      regulator of p-STAT3(Tyr705) oncogenic signaling. However, little is known about
      the molecular mechanism(s) through which SHP-1 regulates EMT during
      hepatocellular carcinoma (HCC) progression. Here we first reported that
      endogenous SHP-1 protein levels were significantly downregulated in cells with
      mesenchymal characteristics and negatively correlated with p-STAT3(Tyr705) and
      vimentin but positively correlated with E-cadherin. SHP-1 overexpression
      abolished transforming growth factor-beta1 (TGF-beta1)-induced p-STAT3(Tyr705)
      and EMT, as well inhibited migration and invasion but further rescued by signal
      transducer and activator of transcription factor 3 (STAT3) overexpression.
      Depletion of SHP-1 could induce a more increase in TGF-beta1-induced p-STAT3(Tyr
      705) and EMT characteristics, further supporting the mechanism that suppression
      of TGF-beta1-induced EMT is dependent on SHP-1-mediated STAT3 inactivation.
      Constitutively overexpressed SHP-1 tyrosine phosphatase activity by D61A-mutated
      SHP-1 markedly reduced TGF-beta1-induced p-STAT3(Tyr705) and EMT features but was
      not altered by C453S catalytic-dead mutant SHP-1. Consequently, SHP-1 acted as a
      powerful suppressor in preventing EMT by exerting its tyrosine phosphatase
      activity that directly downregulated p-STAT3(Tyr705). Most notably, we discovered
      a novel SHP-1 agonist SC-43 better than sorafenib to exert more potent anti-EMT
      effects in vitro as well as anti-metastatic growth in vivo. In conclusion, SHP-1
      is a potent suppressor of HCC EMT and metastasis, thus highlighting that SC-43
      SHP-1 axis may serve as a potential therapeutic target that antagonized p
      STAT3(Tyr705) and thereby prevented HCC EMT and metastasis. 

PMID- 25619840
TI  - C-Jun N-terminal kinases are required for oncolytic adenovirus-mediated
      autophagy.
AB  - Oncolytic adenoviruses, such as Delta-24-RGD (Delta24RGD), are replication
      competent viruses that are genetically engineered to induce selective cancer cell
      lysis. In cancer cells, Delta24RGD induces massive autophagy, which is required
      for efficient cell lysis and adenoviral spread. Understanding the cellular
      mechanisms underlying the regulation of autophagy in cells treated with oncolytic
      adenoviruses may provide new avenues to improve the therapeutic effect. In this
      work, we showed that cancer cells infected with Delta24RGDundergo autophagy
      despite the concurrent activation of the AKT/mTOR pathway. Moreover, adenovirus
      replication induced sustained activation of JNK proteins in vitro. ERK1/2
      phosphorylation remained unchanged during adenoviral infection, suggesting
      specificity of JNK activation. Using genetic ablation and pharmacological
      inactivation of JNK, we unequivocally demonstrated that cells infected with
      Delta24RGD required JNK activation. Thus, genetic co-ablation of JNK1 and JNK2
      genes or inhibition of JNK kinase function rendered Delta24RGD-treated cells
      resistant to autophagy. Accordingly, JNK activation induced phosphorylation of
      Bcl-2 and prevented the formation of Bcl-2/Beclin 1 autophagy suppressor
      complexes. Using an orthotopic model of human glioma xenograft, we showed that
      treatment with Delta24RGD induced phosphorylation and nuclear translocation of
      JNK, as well as phosphorylation of Bcl-2. Collectively, our data identified JNK
      proteins as an essential mechanistic link between Delta24RGD infection and
      autophagy in cancer cells. Activation of JNK without inactivation of the AKT/mTOR
      pathway constitutes a distinct molecular signature of autophagy regulation that
      differentiates Delta24RGD adenovirus from the mechanism used by other oncolytic
      viruses to induce autophagy and provides a new rationale for the combination of
      oncolytic viruses and chemotherapy. 

PMID- 25619839
TI  - Junk DNA and the long non-coding RNA twist in cancer genetics.
AB  - The central dogma of molecular biology states that the flow of genetic
      information moves from DNA to RNA to protein. However, in the last decade this
      dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as
      microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted
      much attention due to their large number and biological significance. Many
      lncRNAs have been identified as mapping to regulatory elements including gene
      promoters and enhancers, ultraconserved regions and intergenic regions of protein
      coding genes. Yet, the biological function and molecular mechanisms of lncRNA in
      human diseases in general and cancer in particular remain largely unknown. Data
      from the literature suggest that lncRNA, often via interaction with proteins,
      functions in specific genomic loci or use their own transcription loci for
      regulatory activity. In this review, we summarize recent findings supporting the
      importance of DNA loci in lncRNA function and the underlying molecular mechanisms
      via cis or trans regulation, and discuss their implications in cancer. In
      addition, we use the 8q24 genomic locus, a region containing interactive SNPs,
      DNA regulatory elements and lncRNAs, as an example to illustrate how single
      nucleotide polymorphism (SNP) located within lncRNAs may be functionally
      associated with the individual's susceptibility to cancer. 

PMID- 25619841
TI  - Targeting HER3 by interfering with its Sec61-mediated cotranslational insertion
      into the endoplasmic reticulum.
AB  - There is increasing evidence implicating human epidermal growth factor receptor 3
      (HER3) in several types of cancer. However, the development of targeted therapies
      to inactivate HER3 function has been a challenging endeavor. Its kinase domain
      functions in allostery not catalysis, and the classical ATP-analog class of
      tyrosine kinase inhibitors fail to inactivate it. Here we describe a novel
      approach that eliminates HER3 expression. The small-molecule cotransin CT8 binds
      the Sec61 translocon and prevents the signal peptide of the nascent HER3 protein
      from initiating its cotranslational translocation, resulting in the degradation
      of HER3 but not the other HER proteins. CT8 treatment suppresses the induction of
      HER3 that accompanies lapatinib treatment of HER2-amplified cancers and
      synergistically enhances the apoptotic effects of lapatinib. The target
      selectivities of cotransins are highly dependent on their structure and the
      signal sequence of targeted proteins and can be narrowed through structure
      function studies. Targeting Sec61-dependent processing identifies a novel
      strategy to eliminate HER3 function. 

PMID- 25619843
TI  - Differential modulation of macrophage response elicited by
      glycoinositolphospholipids and lipophosphoglycan from Leishmania (Viannia) shawi.
AB  - In this work, some aspects of the glycobiology of Leishmania shawi were examined,
      as it is a causative agent of cutaneous leishmaniasis in the New World.
      Additionally, the interaction of L. shawi's main glycoconjugates
      [lipophosphoglycan (LPG) and glycoinositolphospholipids (GIPLs)] with macrophages
      was evaluated in vitro. L. shawi LPG was devoid of side-chains in its repeat
      units, whereas monosaccharide analysis showed that GIPLs were suggestive of
      mannose-rich (type I or hybrid). In order to evaluate the biological roles of
      those molecules, BALB/c resident peritoneal macrophages were incubated with these
      glycoconjugates for 24h, and the levels of nitric oxide (NO), tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-12p70 and IL-10, were determined. In
      general, the GIPLs exhibited a greater proinflammatory role than the LPGs did.
      However, for the first time, the GIPLs from this species were able to trigger the
      production of IL-10, an anti-inflammatory cytokine. In conclusion, L. shawi
      glycoconjugates were able to interact with the innate immune compartment. These
      data reinforce the role of parasite glycoconjugates during parasite and host cell
      interactions. 

PMID- 25619845
TI  - Evaluation of synthesized lipid tethered ligands for surface functionalization of
      polypropylene capillary-channeled polymer fiber stationary phases.
AB  - Polypropylene (PP) capillary-channeled polymer (C-CP) fibers have been used in
      this laboratory as stationary phases for high performance liquid chromatography
      and solid phase extraction of proteins. Greater selectivity has been realized
      through the functionalization of the PP fibers through the physical adsorption of
      commercially available head group-modified poly(ethylene glycol) lipids (PEG
      lipids), where the head group is chosen to affect affinity separations. We refer
      to this general surface modification methodology as lipid tethered ligands
      (LTLs). In this study, LTLs were synthesized by solid phase synthesis. In
      comparison to the commercial PEG-lipids, the synthesized LTLs contain no
      chemically labile phosphate groups. Instead of an ester linkage in the commercial
      lipids, amide functionality was used in the synthesized LTLs to attach the lipids
      and ligands. By use of fluorescence imaging of FITC-labeled LTLs, the synthesized
      LTL was shown to be superior to the commercial LTL in terms of the adsorption
      efficiency to PP C-CP fibers, the resistance to solvent wash from the PP C-CP
      fibers, and their chemical stability under acidic, neutral and basic conditions.
      The PP C-CP fibers functionalized with a synthesized LTL that was biotinylated at
      the head group are shown to be capable of capturing streptavidin from E. coli
      cell lysate more efficiently than the PP C-CP fibers functionalized with the
      commercial biotinylated PEG-lipid. The functionalization of PP C-CP fibers with
      the synthesized LTLs is a simple, but highly efficient, method to generate novel
      stationary phases with a variety of functionalities for solid phase extraction
      and liquid chromatography. 

PMID- 25619842
TI  - SREBP maintains lipid biosynthesis and viability of cancer cells under lipid- and
      oxygen-deprived conditions and defines a gene signature associated with poor
      survival in glioblastoma multiforme.
AB  - Oxygen and nutrient limitation are common features of the tumor microenvironment
      and are associated with cancer progression and induction of metastasis. The
      inefficient vascularization of tumor tissue also limits the penetration of other
      serum-derived factors, such as lipids and lipoproteins, which can be rate
      limiting for cell proliferation and survival. Here we have investigated the
      effect of hypoxia and serum deprivation on sterol regulatory element-binding
      protein (SREBP) activity and the expression of lipid metabolism genes in human
      glioblastoma multiforme (GBM) cancer cells. We found that SREBP transcriptional
      activity was induced by serum depletion both in normoxic and hypoxic cells and
      that activation of SREBP was required to maintain the expression of fatty acid
      and cholesterol metabolism genes under hypoxic conditions. Moreover, expression
      of stearoyl-CoA desaturase, the enzyme required for the generation of mono
      unsaturated fatty acids, and fatty acid-binding protein 7, a regulator of glioma
      stem cell function, was strongly dependent on SREBP function. Inhibition of SREBP
      function blocked lipid biosynthesis in hypoxic cancer cells and impaired cell
      survival under hypoxia and in a three-dimensional spheroid model. Finally, gene
      expression analysis revealed that SREBP defines a gene signature that is
      associated with poor survival in glioblastoma.

PMID- 25619846
TI  - Motor resonance meets motor performance.
AB  - The aim of the present work is to explore which of two different models better
      explains facilitation/interference effects when participants have to
      conditionally react to an observed action with a movement. The Dimensional
      Overlap model assumes two parallel routes, an automatic route and a rule-based
      one, that interact only when the stimulus-set and the response-set share some
      dimensions. In the alternative model, a motor resonance for rule-based reaction,
      the automatic visuo-motor transformation is always an obligatory step that
      provides the correct categorization of the observed action as the input for the
      rule-based route, thus linking the two routes in a serial fashion. We explicitly
      tested which of the hypotheses fits better the data by asking participants to
      perform one of two different actions in a two-choice reaction paradigm. In one
      condition participants were required to perform the opposite action compared to
      the one they saw (COUNTER task: see A->do B, see B->do A), while in the other
      they were required to perform two actions that did not share any dimension with
      the stimulus-set (NEUTRAL task: see A->do C, see B->do D). We predicted an
      advantage for the NEUTRAL task if the Dimensional Overlap model was correct,
      while a similar performance was foreseen if the motor resonance-based model was
      correct. Since the interpretation of these results was not straightforward, we
      conducted a distributional analysis of participants' response accuracies in order
      to understand whether a serial or a general parallel model explained better the
      data. We found clear evidence that participants responded above chance before the
      motor representation of the action observed was activated. We conclude that two
      separate systems in the human brain can transform observed actions in own motor
      representations. One is stimulus-driven, while the second is rule-driven. Likely,
      their activity is mutually independent along parallel pathways. 

PMID- 25619847
TI  - Vestibular contributions to a right-hemisphere network for bodily awareness:
      combining galvanic vestibular stimulation and the "Rubber Hand Illusion".
AB  - An altered sense of one's own body is a common consequence of vestibular damage,
      and also of damage to vestibular networks in the right hemisphere. However, few
      experimental studies have investigated whether vestibular signals contribute to
      bodily awareness. We addressed this issue by combining an established
      experimental model of bodily awareness (Rubber Hand Illusion -RHI) with galvanic
      vestibular stimulation (GVS) in healthy participants. Brief left anodal and right
      cathodal GVS (which predominantly activates vestibular networks in the right
      hemisphere), or right anodal and left cathodal GVS, or sham stimulation were
      delivered at random, while participants experienced either synchronous or
      asynchronous visuo-tactile stimulation of a rubber hand and their own hand. The
      drift in the perceived position of the participant's hand towards the rubber hand
      was used as a proxy measure of the resulting multisensory illusion of body
      ownership. GVS induced strong polarity-dependent effects on this measure of RHI:
      left anodal and right cathodal GVS produced significantly lower proprioceptive
      drift than right anodal and left cathodal GVS. We suggest that vestibular inputs
      influence the multisensory weighting functions that underlie bodily awareness:
      the right hemisphere vestibular projections activated by the left anodal and
      right cathodal GVS increased the weight of intrinsic proprioceptive signals about
      hand position, and decreased the weight of visual information responsible for
      visual capture during the RHI. 

PMID- 25619848
TI  - Distinct functional connectivity of the hippocampus during semantic and phonemic
      fluency.
AB  - Verbal fluency tasks are typically used in neuropsychological practice for
      assessment of language function in a variety of neurological disorders. Recently,
      it has been shown that the hippocampus, a region thought to be exclusive to the
      domain of memory, is also involved in tests of semantic fluency. The present
      study further explores hippocampal contribution to verbal fluency using
      functional Magnetic Resonance Imaging (fMRI) and examining mean activity and
      inter-regional functional connectivity with known task-related brain regions.
      Given the clear lateralization of brain areas involved in language,
      lateralization of hippocampal involvement in semantic and phonemic word fluency
      was also investigated. Different hippocampal recruitment during semantic and
      phonemic fluency was found: greater change in activity was seen during semantic
      fluency, as compared with phonemic fluency. This pattern was obtained in the
      right and the left hippocampus, with no lateralization effects. Functional
      connectivity analyses corroborate the notion of selective contribution of the
      hippocampus to semantic fluency. During the semantic fluency task, connectivity
      levels between the hippocampi and components of the semantic network did not
      differ from connectivity levels within the semantic network. In contrast, during
      the phonemic fluency task, the hippocampi were less correlated with components of
      the phonemic network, as compared to the within phonemic network connectivity.
      Importantly, hippocampal connectivity with the semantic network was task
      dependent and restricted to periods of semantic fluency performance. Altogether,
      results suggest that the right and the left hippocampus are integral components
      of the brain network that selectively supports verbal semantic fluency, but not
      phonemic fluency. 

PMID- 25619849
TI  - Holmes and Horrax (1919) revisited: impaired binocular fusion as a cause of "flat
      vision" after right parietal brain damage - a case study.
AB  - The complete loss of binocular depth perception ("flat vision") was first
      thoroughly described by Holmes and Horrax (1919), and has been occasionally
      reported thereafter in patients with bilateral posterior-parietal lesions. Though
      partial spontaneous recovery occurred in some cases, the precise cause(s) of this
      condition remained obscure for almost a century. Here, we describe a unique
      patient (EH) with a large right-sided occipito-parietal hemorrhage showing a
      complete loss of visual depth perception for several months post-stroke. EH could
      well simultaneously describe multiple visual objects - hence did not show
      simultanagnosia - but at the same time was completely unable to estimate their
      distance from him. In every 3-D visual scene objects appeared equidistant to him,
      thus experiencing a total loss of depth perception ("flat vision"). Neurovisual
      assessments revealed normal functions of the eyes. EH showed bilateral lower
      field loss and a severely impaired binocular convergent fusion, but preserved
      stereopsis. Perceptual re-training of binocular fusion resulted in a progressive
      and finally complete recovery of objective binocular fusion values and subjective
      binocular depth perception in a far-to-near-space, gradient-like manner. In
      parallel, visual depth estimation of relative distances improved, whereas
      stereopsis remained unchanged. Our results show that a complete loss of 3-D depth
      perception can result from an isolated impairment in binocular fusion. On a
      neuroanatomical level, this connection could be explained by a selective lesion
      of area V6/V6A in the medial occipito-parietal cortex that has been associated
      with the integration of visual space coordinates and sustained eye-positions into
      a cyclopean visual 3-D percept. 

PMID- 25619851
TI  - Variability of behavioural responses to transcranial magnetic stimulation:
      Origins and predictors.
AB  - Transcranial magnetic stimulation (TMS) may modulate the excitability of local
      cortical stimulation sites and distant functionally interconnected regions for
      minutes, hours or even days. The effects of TMS suggest that it not only acts on
      activity of the stimulated area, but also on its connections with remote areas.
      Due to these properties one of the main rationales for the application of TMS in
      stroke patients is to improve imbalance in interhemispheric inhibition. However,
      given that TMS may have excitatory or inhibitory effects the impact of
      stimulation is not easy to predict. In this review, we discuss the different
      factors that determine the magnitude and quality of physiological and behavioural
      responses to TMS. Whether TMS is mainly excitatory or inhibitory not only depends
      on the parameters of stimulation such as pulse frequency and duration, but also
      on baseline activity of neural tissue before stimulation, or even on cognitive
      factors such as attention. A major challenge for the application of TMS as
      therapy method is to identify predictors of positive effects in individual
      patients. Neuroimaging studies measuring hemodynamic or electrophysiological
      responses show that changes in interhemispheric competition or adaptations of
      functional networks in patients with focal brain lesions may predict the
      individual response to brain stimulation. Such techniques have the potential to
      select the most appropriate among different intervention methods for an
      individual patient. 

PMID- 25619850
TI  - Getting on the same page: the neural basis for social coordination deficits in
      behavioral variant frontotemporal degeneration.
AB  - For social interactions to be successful, individuals must establish shared
      mental representations that allow them to reach a common understanding and "get
      on the same page". We refer to this process as social coordination. While
      examples of social coordination are ubiquitous in daily life, relatively little
      is known about the neuroanatomic basis of this complex behavior. This is
      particularly true in a language context, as previous studies have used overly
      complex paradigms to study this. Although traditional views of language
      processing and the recent interactive-alignment account of conversation focus on
      peri-Sylvian regions, our model of social coordination predicts prefrontal
      involvement. To test this hypothesis, we examine the neural basis of social
      coordination during conversational exchanges in non-aphasic patients with
      behavioral variant frontotemporal degeneration (bvFTD). bvFTD patients show
      impairments in executive function and social comportment due to disease in
      frontal and anterior temporal regions. To investigate social coordination in
      bvFTD, we developed a novel language-based task that assesses patients' ability
      to convey an object's description to a conversational partner. Experimental
      conditions manipulated the amount of information shared by the participant and
      the conversational partner, and the associated working memory demands. Our
      results indicate that, although patients did not have difficulty identifying the
      features of the objects, they did produce descriptions that included insufficient
      or inappropriate adjectives and thus struggled to communicate effectively.
      Impaired performance was related to gray matter atrophy particularly in medial
      prefrontal and orbitofrontal cortices. Our findings suggest an important role for
      non-language brain areas that belong to a large-scale neurocognitive network for
      social coordination. 

PMID- 25619852
TI  - In situ characterization of Cu-Co oxides for catalytic application.
AB  - In situ emission and absorption FTIR methods were employed to characterize the
      spatially resolved structure of binary Co-Cu oxides for low-temperature oxidation
      of CO and propene. Co-Cu oxide catalysts were controllably synthesized by pulsed
      spray evaporation chemical vapor deposition. XRD, FTIR, XPS, UV-vis and helium
      ion microscopy (HIM) were employed to characterize the as-prepared thin films in
      terms of structure, composition, optical and thermal properties as well as
      morphology. In situ emission FTIR spectroscopy indicates that Co3O4, CuCo2O4 and
      CuO are thermally stable at 650, 655 and 450  degrees C, respectively. The
      catalytic tests with absorption FTIR display that the involvement of Co-Cu oxides
      can initiate CO and C3H6 oxidation at lower temperatures. The results indicate
      that in situ emission and absorption FTIR are useful techniques to explore the
      thermal properties and catalytic performance of functional materials, allowing
      many potential applications in tailoring their temporally and spatially resolved
      structure-property relationships. 

PMID- 25619854
TI  - Explorative and targeted neuroproteomics in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain
      regions involved in memory consolidation and other higher brain functions.
      Neuropathologically, the disease is characterized by accumulation of a 42 amino
      acid peptide called amyloid beta (Abeta42) in extracellular senile plaques,
      intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary
      tangles, and neuronal and axonal degeneration and loss. Biomarker assays
      capturing these pathologies have been developed for use on cerebrospinal fluid
      samples but there are additional molecular pathways that most likely contribute
      to the neurodegeneration and full clinical expression of AD. One way of learning
      more about AD pathogenesis is to identify novel biomarkers for these pathways and
      examine them in longitudinal studies of patients in different stages of the
      disease. Here, we discuss targeted proteomic approaches to study AD and AD
      related pathologies in closer detail and explorative approaches to discover novel
      pathways that may contribute to the disease. This article is part of a Special
      Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. 

PMID- 25619853
TI  - Lactate production by the mammalian blastocyst: manipulating the microenvironment
      for uterine implantation and invasion?
AB  - The mammalian blastocyst exhibits a high capacity for aerobic glycolysis, a
      metabolic characteristic of tumours. It has been considered that aerobic
      glycolysis is a means to ensure a high carbon flux to fulfil biosynthetic
      demands. Here, alternative explanations for this pattern of metabolism are
      considered. Lactate creates a microenvironment of low pH around the embryo to
      assist the disaggregation of uterine tissues to facilitate trophoblast invasion.
      Further it is proposed that lactate acts as a signalling molecule (especially at
      the reduced oxygen tension present at implantation) to elicit bioactive VEGF
      recruitment from uterine cells, to promote angiogenesis. Finally it is suggested
      that the region of high lactate/low pH created by the blastocyst modulates the
      activity of the local immune response, helping to create immune tolerance.
      Consequently, the mammalian blastocyst offers a model to study the role of
      microenvironments, and how metabolites and pH are used in signalling. 

PMID- 25619855
TI  - Multidimensional electrostatic repulsion-hydrophilic interaction chromatography
      (ERLIC) for quantitative analysis of the proteome and phosphoproteome in clinical
      and biomedical research.
AB  - Quantitative proteomics and phosphoproteomics have become key disciplines in
      understanding cellular processes. Fundamental research can be done using cell
      culture providing researchers with virtually infinite sample amounts. In
      contrast, clinical, pre-clinical and biomedical research is often restricted to
      minute sample amounts and requires an efficient analysis with only micrograms of
      protein. To address this issue, we generated a highly sensitive workflow for
      combined LC-MS-based quantitative proteomics and phosphoproteomics by refining an
      ERLIC-based 2D phosphoproteomics workflow into an ERLIC-based 3D workflow
      covering the global proteome as well. The resulting 3D strategy was successfully
      used for an in-depth quantitative analysis of both, the proteome and the
      phosphoproteome of murine cytomegalovirus-infected mouse fibroblasts, a model
      system for host cell manipulation by a virus. In a 2-plex SILAC experiment with
      150 MUg of a tryptic digest per condition, the 3D strategy enabled the
      quantification of ~75% more proteins and even ~134% more peptides compared to the
      2D strategy. Additionally, we could quantify ~50% more phosphoproteins by non
      phosphorylated peptides, concurrently yielding insights into changes on the
      levels of protein expression and phosphorylation. Beside its sensitivity, our
      novel three-dimensional ERLIC-strategy has the potential for semi-automated
      sample processing rendering it a suitable future perspective for clinical, pre
      clinical and biomedical research.

PMID- 25619856
TI  - Synthesis, spectroscopic, thermal and structural properties of [M(3
      aminopyridine)2Ni(MU-CN)2(CN)2]n (M(II)=Co and Cu) heteropolynuclear cyano
      bridged complexes.
AB  - Two novel cyano-bridged heteropolynuclear complexes, [Co(3-aminopyridine)2Ni(MU
      CN)2(CN)2]n and [Cu(3-aminopyridine)2Ni(MU-CN)2(CN)2]n have been synthesized and
      characterized by elemental, thermal, FT-IR and FT-Raman spectroscopies. The
      structures of complexes have been determined by X-ray powder diffraction. The FT
      IR and FT-Raman spectra of complexes have been recorded in the region of 3500
      400cm(-1) and 3500-100cm(-1), respectively. General information was acquired
      about structural properties of these complexes from FT-IR and FT-Raman spectra by
      considering changes at characteristic peaks of the cyano group and 3AP. The
      splitting of the nu(CN) stretching bands in the FT-IR spectra for complexes
      indicates the presence of terminal and bridging cyanides. The thermal behaviors
      of these complexes have been also investigated in the range of 25-950 degrees C
      using TG and DTG methods. Magnetic susceptibility measurements were made at room
      temperature using Gouy-balance.

PMID- 25619857
TI  - Alteration of methotrexate binding to human serum albumin induced by oxidative
      stress. Spectroscopic comparative study.
AB  - Changes of oxidative modified albumin conformation by comparison of non-modified
      (HSA) and modified (oHSA) human serum albumin absorption spectra, Red Edge
      Excitation Shift (REES) effect and fluorescence synchronous spectra were
      investigated. Studies of absorption spectra indicated that changes in the value
      of absorbance associated with spectral changes in the region from 200 to 250nm
      involve structural alterations related to variations in peptide backbone
      conformation. Analysis of the REES effect allowed for the observation of changes
      caused by oxidation in the region of the hydrophobic pocket containing the
      tryptophanyl residue. Synchronous fluorescence spectroscopy confirmed changes of
      the position of the tryptophanyl and tyrosil residues fluorescent band. Effect of
      oxidative stress on binding of methotrexate (MTX) was investigated by
      spectrofluorescence, UV-VIS and (1)HNMR spectroscopy. MTX caused the fluorescence
      quenching of non-modified (HSA) and modified (oHSA) human serum albumin molecule.
      The values of binding constants, Hill's coefficients and a number of binding
      sites in the protein molecule in the high affinity binding site were calculated
      for the binary MTX-HSA and MTX-oHSA systems. For these systems, qualitative
      analysis in the low affinity binding sites was performed with the use of the
      (1)HNMR technique. 

PMID- 25619858
TI  - Optical luminescence studies of the ethyl xanthate adsorption layer on the
      surface of sphalerite minerals.
AB  - In this work we propose optical luminescence measurements as a method to evaluate
      the kinetics of adsorption processes. Measurement of the intensity of the
      integral optical radiation obtained from the mineral-xanthate interface layer,
      stimulated with a monochromatic pulsating optical signal, as a function of time
      were made. The luminescence radiation was obtained from the thin interface layer
      formed at the separation surface between the sphalerite natural mineral and
      potassium ethyl xanthate solution, for different solution concentrations and pH
      es at the constant industry standard temperature. This method enabled us to
      determine the time to achieve dynamic equilibrium in the formation of the
      interface layer of approximately 20min, gaining information on the adsorption
      kinetics in the case of xanthate on mineral surface and leading to the
      optimization of the industrial froth flotation process.

PMID- 25619859
TI  - FT-IR spectroscopy and multivariate analysis as an auxiliary tool for diagnosis
      of mental disorders: Bipolar and schizophrenia cases.
AB  - In this study, a methodology based on Fourier-transform infrared spectroscopy and
      principal component analysis and partial least square methods is proposed for the
      analysis of blood plasma samples in order to identify spectral changes correlated
      with some biomarkers associated with schizophrenia and bipolarity. Our main goal
      was to use the spectral information for the calibration of statistical models to
      discriminate and classify blood plasma samples belonging to bipolar and
      schizophrenic patients. IR spectra of 30 samples of blood plasma obtained from
      each, bipolar and schizophrenic patients and healthy control group were
      collected. The results obtained from principal component analysis (PCA) show a
      clear discrimination between the bipolar (BP), schizophrenic (SZ) and control
      group' (CG) blood samples that also give possibility to identify three main
      regions that show the major differences correlated with both mental disorders
      (biomarkers). Furthermore, a model for the classification of the blood samples
      was calibrated using partial least square discriminant analysis (PLS-DA),
      allowing the correct classification of BP, SZ and CG samples. The results
      obtained applying this methodology suggest that it can be used as a complimentary
      diagnostic tool for the detection and discrimination of these mental diseases.

PMID- 25619861
TI  - GnRH agonist reduces estrogen receptor dimerization in GT1-7 cells: evidence for
      cross-talk between membrane-initiated estrogen and GnRH signaling.
AB  - 17beta-estradiol (E2), a key participant on the initiation of the LH surge,
      exerts both positive and negative feedback on GnRH neurons. We sought to
      investigate potential interactions between estrogen receptors alpha (ERalpha) and
      beta (ERbeta) and gonadotropin releasing hormone receptor (GnRH-R) in GT1-7
      cells. Radioligand binding studies demonstrated a significant decrease in
      saturation E2 binding in cells treated with GnRH agonist. Conversely, there was a
      significant reduction in GnRH binding in GT1-7 cells treated with E2. In BRET(1)
      experiments, ERalpha-ERalpha dimerization was suppressed in GT1-7 cells treated
      with GnRH agonist (p < 0.05). There was no evidence of direct interaction between
      ERs and GnRH-R. This study provides the first evidence of reduced ERalpha
      homodimerization by GnRH agonist. Collectively, these findings demonstrate
      significant cross-talk between membrane-initiated GnRH and E2 signaling in GT1-7
      cells. 

PMID- 25619862
TI  - Caries recurrence after treatment under general anaesthesia for early childhood
      caries: a retrospective cohort study.
AB  - AIM: To evaluate rates of caries relapse and explore factors affecting relapse
      rates after comprehensive dental treatment under general anaesthesia (GA).
      METHODS: A retrospective cohort study of children <=6 years of age at the time of
      reference GA (RGA) who were in an anaesthetic low risk category [American Society
      of Anesthesiologists (ASA) classification 1 or 2], and had completed 36 months
      follow-up period was conducted. Patients' demographics and dental records were
      collected. Associations between relapse rate and different factors affecting
      relapse rates were evaluated. RESULTS: A total of 278 children with mean age of
      47 +/- 14 months were included. Over 8 % of children had more than one GA, 88 %
      attended their post-operative follow-up appointment and 45 % returned for all
      recall appointments over 3 years. During the 3-year follow-up, the relapse rate
      was 22 %. ASA-2 children and those with less than full primary dentition present
      at the RGA were more than twice as likely to experience caries relapse as
      compared to ASA-1 children (OR = 2.46, 95 % CI 1.33-4.56) and those with mixed
      dentition present at the RGA (OR = 2.74, 95 % CI 1.27-5.91). CONCLUSION: ASA-2
      health status and having less than a full primary dentition were major predictors
      of caries relapse after dental treatment under GA.

PMID- 25619863
TI  - A systematic review on the patient perception of periodontal treatment using air
      polishing devices.
AB  - OBJECTIVES: Air polishing devices are used as an alternative to traditional
      instrumentation of the root surface. The objective of the systematic review was
      to analyse patient perception, that is pain and discomfort during treatment with
      air polishing devices in periodontal therapy. METHODS: The electronic databases
      MEDLINE, EMBASE and the Cochrane library were screened for studies published
      through 18th November 2013. Patient perception served as primary outcome.
      RESULTS: Of the 1266 abstracts screened, nine studies reporting data on patient
      perception using a visual analogue scale or a patient interview were included in
      the analysis. Different air polishing powders consisting of sodium bicarbonate,
      glycine or erythritol were used. Reported discomfort of non-surgical periodontal
      therapy was consistently equal or lower when air polishing powders consisting of
      glycine or erythritol were applied compared with root surface instrumentation
      using hand instruments or ultrasonic devices. CONCLUSION: Air polishing with
      powders consisting of glycine seems to be associated with less discomfort during
      non-surgical periodontal therapy, that is supra- and subgingival air polishing.

PMID- 25619865
TI  - Effect of caffeine on intrinsic mechanical properties of normal and malignant
      hyperthermia-susceptible muscle.
AB  - INTRODUCTION: Malignant hyperthermia (MH) is a potentially lethal anesthesic
      complication. Pathological symptoms develop after exposure to triggering
      substances. It remains uncertain whether cellular alterations pre-exist.
      Mechanical properties of isolated muscle bundles were examined before and after
      exposure to a triggering substance. METHODS: With prior written consent, muscle
      bundles of 12 MH-susceptible (MHS) and 56 MH-nonsusceptible (MHN) individuals
      were examined before and after exposure to incremental doses of caffeine.
      Mechanical properties (baseline tension, peak tension, time to peak tension, and
      relaxation time) were measured. Contraction and relaxation derivatives and
      contraction-relaxation coupling were calculated and analyzed. RESULTS: Mechanical
      properties were not different between the groups before caffeine application.
      Caffeine increased peak tension in both groups and baseline tension only in MHS
      muscle bundles; relaxation time/derivative and contraction-relaxation coupling
      were prolonged. CONCLUSIONS: Cellular changes seen in MH are not pre-existing.
      Exposure to triggering substance impairs relaxation in MHS muscle.

PMID- 25619867
TI  - Inhibition of the enhancement of infection of human immunodeficiency virus by
      semen-derived enhancer of virus infection using amyloid-targeting polymeric
      nanoparticles.
AB  - The semen-derived enhancer of virus infection (SEVI) is a natural amyloid
      material that has been shown to substantially increase viral attachment and
      infectivity of HIV in cells. We previously reported that synthetic monomeric and
      oligomeric amyloid-targeting molecules could form protein-resistive coatings on
      SEVI and inhibit SEVI- and semen-mediated enhancement of HIV infectivity. While
      oligomeric amyloid-binding compounds showed substantial improvement in apparent
      binding to SEVI compared to monomeric compounds, we observed only a modest
      correlation between apparent binding to SEVI and activity for reducing SEVI
      mediated HIV infection. Here, we synthesized amyloid-binding polyacrylate-based
      polymers and polymeric nanoparticles of comparable size to HIV virus particles
      (~150 nm) to assess the effect of sterics on the inhibition of SEVI-mediated
      enhancement of HIV infectivity. We show that these polymeric materials exhibit
      excellent capability to reduce SEVI-mediated enhancement of HIV infection, with
      the nanoparticles exhibiting the greatest activity (IC50 value of ~4 MUg/mL, or
      59 nM based on polymer) of any SEVI-neutralizing agent reported to date. The
      results support that the improved activity of these nanomaterials is likely due
      to their increased size (diameters = 80-200 nm) compared to amyloid-targeting
      small molecules and that steric interactions may play as important a role as
      binding affinity in inhibiting viral infection mediated by SEVI amyloids. In
      contrast to the previously reported SEVI-neutralizing, amyloid-targeting
      molecules (which required concentrations at least 100-fold above the Kd to
      observe activity), the approximate 1:1 ratio of apparent Kd to IC50 for activity
      of these polymeric materials suggests the majority of polymer molecules that are
      bound to SEVI contribute to the inhibition of HIV infectivity enhanced by SEVI.
      Such size-related effects on physical inhibition of protein-protein interactions
      may open further opportunities for the use of targeted nanomaterials in disease
      intervention. 

PMID- 25619868
TI  - Consensus guidelines on plasma cell myeloma minimal residual disease analysis and
      reporting.
AB  - BACKGROUND: Major heterogeneity between laboratories in flow cytometry (FC)
      minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome.
      Cytometry societies such as the International Clinical Cytometry Society and the
      European Society for Clinical Cell Analysis recognize a strong need to establish
      minimally acceptable requirements and recommendations to perform such complex
      testing. METHODS: A group of 11 flow cytometrists currently performing FC testing
      in MM using different instrumentation, panel designs (>= 6-color) and analysis
      software compared the procedures between their respective laboratories and
      reviewed the literature to propose a consensus guideline on flow-MRD analysis and
      reporting in MM. RESULTS/CONCLUSION: Consensus guidelines support i) the use of
      minimum of five initial gating parameters (CD38, CD138, CD45, forward, and
      sideward light scatter) within the same aliquot for accurate identification of
      the total plasma cell compartment; ii) the analysis of potentially aberrant
      phenotypic markers and to report the antigen expression pattern on neoplastic
      plasma cells as being reduced, normal or increased, when compared to a normal
      reference plasma cell immunophenotype (obtained using the same instrument and
      parameters); and iii) the percentage of total bone marrow plasma cells plus the
      percentages of both normal and neoplastic plasma cells within the total bone
      marrow plasma cell compartment, and over total bone marrow cells. Consensus
      guidelines on minimal current and future MRD analyses should target a lower limit
      of detection of 0.001%, and ideally a limit of quantification of 0.001%, which
      requires at least 3 * 10(6) and 5 * 10(6) bone marrow cells to be measured,
      respectively.

PMID- 25619869
TI  - Preparation of molecule-responsive microsized hydrogels via photopolymerization
      for smart microchannel microvalves.
AB  - Microdevices designed for practical environmental pollution monitoring need to
      detect specific pollutants such as dioxins. Bisphenol A (BPA) has been widely
      used as a monomer for the synthesis of polycarbonate and epoxy resins. However,
      the recent discovery of its high potential ability to disrupt human endocrine
      systems has made the development of smart systems and microdevices for its
      detection and removal necessary. Molecule-responsive microsized hydrogels with
      beta-cycrodextrin (beta-CD) as ligands are prepared by photopolymerization using
      a fluorescence microscope. The molecule-responsive micro-hydrogels show ultra
      quick shrinkage in response to target BPA. Furthermore, the flow rate of a
      microchannel is autonomously regulated by the molecule-responsive shrinking of
      their hydrogels as smart microvalves. 

PMID- 25619870
TI  - Physical matching of metals: grain orientation association at fracture edge.
AB  - The objective of this study was to examine whether surface crystal orientation
      can be used to associate or differentiate metal fracture fragments. The
      orientations of individual crystals and crystals across the fracture plane were
      measured on polished steel and iron alloy surfaces using Electron Backscattered
      Diffraction/ Orientation Imaging Microscopy (EBSD/OIM). This investigation
      examined crystallographic characteristics within a metal. This study showed that
      for transgranular fracture, it is feasible that pieces of grains could be
      associated across the fracture surface with the difference in orientation between
      grains (misorientation) along a length sequence of grain orientations on one side
      of the fracture surface to associate the other side of a fracture surface.
      Regarding pair comparisons of crystals on fracture surfaces, it was estimated
      that the probability for an ordered sequence of six distinct oriented grains
      along a fracture surface to occur again is about 1 in 4.82 (10)(30) or 2.07 (10)(
      31).

PMID- 25619871
TI  - Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with
      chronic hepatitis C virus genotype 1 infection.
AB  - BACKGROUND: An all-oral, pegylated interferon (pegIFN)-free and ribavirin (RBV)
      free single-tablet of ledipasvir (LDV) and sofosbuvir (SOF) is now approved for
      the treatment of patients infected with hepatitis C virus (HCV) genotype 1. AIM:
      To estimate the health economic outcomes for LDV/SOF compared with current
      treatments in US patients infected with HCV genotype 1. METHODS: A hybrid
      decision-tree and Markov state-transition model was developed. For a cohort of
      10,000 patients, the model captured outcomes for several pairings of LDV/SOF with
      comparators, including long-term health outcomes, number need to treat, life
      years gained, quality-adjusted life-years (QALYS) gained, incremental cost
      effectiveness ratios and costs per sustained virologic response (SVR). Patients
      with different levels of treatment experience and different cirrhosis stages were
      included. RESULTS: LDV/SOF decreased the number of advanced liver disease cases
      by 0-93% compared with current regimens or no treatment in treatment-naive
      patients. In treatment-experienced [pegIFN plus ribavirin (PR) or protease
      inhibitor (PI) + PR] patients, treatment with LDV/SOF decreased the incidence of
      advanced liver disease complications in most of the cases analysed, except SOF +
      SMV. For all patient sub-cohorts, LDV/SOF was associated with the lowest 1-year
      costs per SVR and, with regard to lifetime incremental costs per QALY gained, was
      either dominant or the most cost-effective treatment. Overall, treatment
      initiation at earlier stages of liver fibrosis resulted in improved health
      economic outcomes. CONCLUSION: LDV/SOF is associated with more favourable short-
      and long-term health economic outcomes compared with current therapies for
      patients across all levels of treatment experience and cirrhosis stages.

PMID- 25619873
TI  - Pulmonary embolism in a patient of tetralogy of Fallot: a diagnostic challenge.
AB  - A 46-year-old male patient with tetralogy of Fallot presented to the emergency
      department with progressive dyspnea for 3 days. The dyspnea was refractory to
      treatment for tet spells. Pulmonary embolism (PE) was subsequently diagnosed by
      computed tomography, and the patient was successfully treated with
      heparinization. Chronic hypoxemia-induced secondary polycythemia and the
      consequent increase in blood hyperviscosity predisposed this patient to PE. This
      case reminds us of the similarity in clinical presentation between PE and tet
      spells.

PMID- 25619872
TI  - IL-35 and Autoimmunity: a Comprehensive Perspective.
AB  - Interleukin 35 (IL-35) is the most recently identified member of the IL-12 family
      of cytokines and offers the potential to be a target for new therapies for
      autoimmune, inflammatory, and infectious diseases. Similar to other members of
      the IL-12 family including IL-12, IL-23, and IL-27, IL-35 is composed of a
      heterodimer of alpha and beta chains, which in the case of IL-35 are the p35 and
      Epstein-Barr virus-induced gene 3 (EBI3) proteins. However, unlike its
      proinflammatory relatives, IL-35 has immunosuppressive effects that are mediated
      through regulatory T and B cells. Although there are limited data available
      regarding the role of IL-35 in human autoimmunity, several murine models of
      autoimmunity suggest that IL-35 may have potent effects in regulating
      immunoreactivity via IL-10-dependent mechanisms. We suggest that similar effects
      are operational in human disease and IL-35-directed therapies hold significant
      promise. In particular, we emphasize that IL-35 has immunosuppressive ability
      that are mediated via regulatory T and B cells that are IL-10 dependent. Further,
      although deletion of IL-35 does not result in spontaneous breach of tolerance,
      recombinant IL-35 can improve autoimmune responses in several experimental
      models. 

PMID- 25619874
TI  - Daily fluid intake and outcomes in kidney recipients: post hoc analysis from the
      randomized ABCAN trial.
AB  - Generous and even excessive fluid intake is routinely recommended to kidney
      transplant recipients despite minimal evidence to support this practice. We
      hypothesized that increased fluid intake, ascertained by 24-h urine volume
      output, may adversely affect graft outcomes as it would impose an extra workload
      on a limited number of nephrons. Kidney transplant recipients who were randomized
      to losartan vs. placebo in the Angiotensin II Blockade for Chronic Allograft
      Nephropathy (ABCAN) trial (n = 153) underwent baseline, five-yr biopsies, and
      annual iothalamate glomerular filtration rate assessment. Recipients with higher
      urine volume at randomization had higher urinary sodium and also higher urinary
      protein. The proportion using diuretics or CNI based regimens were similar across
      urinary volume tertiles. The highest urinary volume tertile (>2.56 L/d) did not
      predict the development of interstitial volume doubling or end-stage renal
      disease (ESRD) from interstitial fibrosis/tubular atrophy (OR = 3.52, 95% CI 0.4,
      31.24, p = 0.26), interstitial volume doubling or all-cause ESRD (OR = 7.04, 95%
      CI 0.66, 74.87, p = 0.11), and was not associated with the conventional endpoint
      of doubling serum creatinine, all-cause ESRD, or death (OR = 0.89, 95% CI 0.21,
      3.71, p = 0.87). These results suggest that the current practice of liberal fluid
      intake may not be beneficial in low risk and mostly Caucasian transplant
      recipients.

PMID- 25619875
TI  - Application of "hydrogen bonding interaction" in new drug development: design,
      synthesis, antiviral activity, and SARs of thiourea derivatives.
AB  - A series of simple thiourea derivatives were designed based on the structure of
      natural product harmine and lead compound and synthesized from amines in one
      step. The antiviral activity of these thiourea derivatives was evaluated. Most of
      them exhibited significantly higher anti-TMV activity than commercial plant
      virucides ribavirin, harmine, and lead compound. The hydrogen bond was found to
      be important but not the more the better. The optimal compound (R,R)-20 showed
      the best anti-TMV activity in vitro and in vivo (in vitro activity, 75%/500
      MUg/mL and 39%/100 MUg/mL; inactivation activity, 71%/500 MUg/mL and 35%/100
      MUg/mL; curative activity, 73%/500 MUg/mL and 37%/100 MUg/mL; protection
      activity, 69%/500 MUg/mL and 33%/100 MUg/mL), which is significantly higher than
      that of Ningnanmycin. The systematic study provides strong evidence that these
      simple thiourea derivatives could become potential TMV inhibitors.

PMID- 25619876
TI  - Pseudoepitheliomatous hyperplasia mimicking invasive squamous cell carcinoma in
      extranodal natural killer/T-cell lymphoma: a report of 34 cases.
AB  - AIMS: Pseudoepitheliomatous hyperplasia (PEH) is defined as a pattern of
      epidermal reaction. However, it has not yet been extensively documented in
      extranodal natural killer/T-cell lymphoma (ENKTL). The aim of our study was to
      analyse a series of ENKTLs concomitant with PEH mimicking squamous cell carcinoma
      (SCC). METHODS AND RESULTS: We analysed 34 cases of ENKTL with PEH. In our study,
      the incidence of PEH was 3.8% in ENKTLs diagnosed over a 13-year period. All 34
      cases presented with PEH, appearing as tongue-like projections of squamous
      epithelium into the underlying submucosa/dermis with variable depths and jagged
      borders. The keratinocytes sometimes showed a minor degree of cytological atypia,
      mostly in the stratum basale, and keratinocyte necrosis was absent. Atypical
      mitoses and a high nuclear/cytoplasmic ratio were absent. The submucosa and the
      squamous cell cords were also permeated by atypical lymphocytes. CONCLUSIONS:
      ENKTL can be associated with PEH, and the atypical lymphoid cell population can
      be highly subtle, and therefore may be easily mistaken for SCC, leading to
      inappropriate therapy. A correct diagnosis requires awareness and recognition of
      this pitfall by recognizing the associated conditions listed above, which
      distinguish PEH from SCC.

PMID- 25619878
TI  - Elevated transaminases are common in children on prophylactic treatment for
      tuberculosis.
AB  - AIM: The aim of this study was to assess the prevalence of elevated transaminase
      levels in children undergoing prophylactic treatment for tuberculosis (TB)
      infection. METHODS: All children living in a geographically defined area, who
      started TB prophylaxis during 2009-2011, were included. Data on background
      factors, treatment regimes and transaminase levels at baseline and follow-up were
      collected retrospectively. RESULTS: Of the 277 children who were treated, 113
      (41%) had elevated transaminase levels. Of these, 97 (35%) had levels that were
      less than three times the upper limit of the normal range and 16 (6%) had levels
      that were more than three times the normal range. Four patients had to
      discontinue isoniazid treatment and were successfully switched to rifampicin. In
      17 patients, the highest transaminase peak did not occur until after 6 months of
      treatment. Elevated transaminases were significantly more common in patients
      below 9 years of age (62%) than in those aged 10-18 years (28%). Transaminases
      were elevated in 44% of all boys and 36% of all girls (p = 0.17). CONCLUSION:
      Transaminase elevation was common in children receiving prophylactic treatment
      for TB and started at different points throughout the treatment period. Younger
      patients faced an increased risk. Regular blood tests are recommended throughout
      treatment.

PMID- 25619877
TI  - Was a decision made? An assessment of patient-clinician discordance in medical
      oncology encounters.
AB  - BACKGROUND: Shared decision making is promoted to improve cancer care quality.
      Patients and clinicians may have different ideas about what constitutes a cancer
      care decision, which may limit the validity of self-reported measures of shared
      decision making. We sought to estimate the extent to which patients and
      clinicians agree on whether a cancer care decision was made during an outpatient
      encounter. METHODS: We surveyed patients and clinicians immediately after an
      oncology encounter at a large, tertiary medical centre and calculated agreement
      in response to the single-item question, 'Was a specific decision about cancer
      care made during the appointment today?' Answer options were 'yes' and 'no'.
      Participants were 315 oncology patients, with any solid tumour malignancy and at
      any stage of management, and their clinicians (22 staff oncologists, nine senior
      fellows and five nurse practitioners). RESULTS: Patients and clinicians reported
      having made a cancer care decision in 184 (58%) and 174 (55%) of encounters,
      respectively. They agreed on whether a cancer care decision was made in 213 (68%)
      of encounters (chance-adjusted agreement was 0.34); in 56 of the 102 discordant
      encounters, the patient reported making a decision while the clinician did not.
      We found no significant correlates with discordance. CONCLUSIONS: Patients and
      clinicians do not always agree on whether a cancer care decision was made. As
      such, measures that ask patients and/or clinicians to evaluate a decision-making
      process or outcome may be methodologically insufficient when they do not
      explicitly orient respondents towards the thing they are being asked to assess.

PMID- 25619880
TI  - S-adenosylmethionine blocks osteosarcoma cells proliferation and invasion in
      vitro and tumor metastasis in vivo: therapeutic and diagnostic clinical
      applications.
AB  - Osteosarcoma (OS) is an aggressive and highly metastatic form of primary bone
      cancer affecting young children and adults. Previous studies have shown that
      hypomethylation of critical genes is driving metastasis. Here, we examine whether
      hypermethylation treatment can block OS growth and pulmonary metastasis. Human OS
      cells LM-7 and MG-63 were treated with the ubiquitous methyl donor S
      adenosylmethionine (SAM) or its inactive analog S-adenosylhomocystine (SAH) as
      control. Treatment with SAM resulted in a dose-dependent inhibition of tumor cell
      proliferation, invasion, cell migration, and cell cycle characteristics.
      Inoculation of cells treated with 150 MUmol/L SAM for 6 days into tibia or via
      intravenous route into Fox Chase severe combined immune deficient (SCID) mice
      resulted in the development of significantly smaller skeletal lesions and a
      marked reduction in pulmonary metastasis as compared to control groups. Epigenome
      wide association studies (EWAS) showed differential methylation of several genes
      involved in OS progression and prominent signaling pathways implicated in bone
      formation, wound healing, and tumor progression in SAM-treated LM-7 cells. Real
      time polymerase chain reaction (qPCR) analysis confirmed that SAM treatment
      blocked the expression of several prometastatic genes and additional genes
      identified by EWAS analysis. Immunohistochemical analysis of normal human bone
      and tissue array from OS patients showed significantly high levels of expression
      of one of the identified gene platelet-derived growth factor alpha (PDGFA). These
      studies provide a possible mechanism for the role of DNA demethylation in the
      development and metastasis of OS to provide a rationale for the use of
      hypermethylation therapy for OS patients and identify new targets for monitoring
      OS development and progression.

PMID- 25619882
TI  - EMT blockage strategies: Targeting Akt dependent mechanisms for breast cancer
      metastatic behaviour modulation.
AB  - Epithelial Mesenchymal Transition (EMT) is an event where epithelial cells
      acquire mesenchymal-like phenotype. EMT can occur as a physiological phenomenon
      during tissue development and wound healing, but most importantly, EMT can confer
      highly invasive properties to epithelial carcinoma cells. The impairment of E
      cadherin expression, an essential cell-cell adhesion protein, together with an
      increase in the expression of mesenchymal markers, such as N-cadherin, vimentin,
      and fibronectin, characterize the EMT process and are usually correlated with
      tumor migration, and metastization. A wide range of micro-environmental and
      intracellular factors regulate tumor development and progression. The dynamic
      cross-talk between the adhesion-related proteins such as E-cadherin and the EMT
      related transcription factors, with special focus on TWIST, will be discussed
      here, with the aim of finding a suitable biological pathway to be used as
      potential target for cancer therapy. Emerging concepts such as the role of the
      PI3K/AKT/TWIST pathway in the regulation of the E-cadherin expression will be
      highlighted, since it seems to be consistently involved in cells EMT. The well
      known efficacy of the RNA interference as a tool to silence the expression of
      specific proteins has come into focus as a strategy to control different tumor
      sub-populations. Despite the oligonucleotides enormous sensitivity and low in
      vivo stability, new (nano)technological solutions are expected to enable RNAi
      clinical application in cancer therapy.

PMID- 25619883
TI  - T cell tuning for tumour therapy: Enhancing effector function and memory
      potential of therapeutic T cells.
AB  - The genetic engineering of T cells can lead to enhanced immune-mediated tumour
      destruction and harbors a great potential for the treatment of cancer. Recent
      efforts have centered on the design of receptors to re-direct the specificity of
      T cells towards tumour antigens by means of viral gene transfer. This strategy
      has shown great success in a number of phase one clinical trials. However, there
      are still challenges to overcome. On the one hand, T cell function can be further
      improved to optimize the therapeutic outcome. On the other hand, so called safety
      switches are required to deal with possible on and off target toxicities. In this
      review, we will give a brief summary of the success and risks of T cell gene
      therapy before discussing in detail current strategies to enhance effector
      function, persistence and safety of adoptively transferred T cells. 

PMID- 25619881
TI  - Effects of ceftriaxone on GLT1 isoforms, xCT and associated signaling pathways in
      P rats exposed to ethanol.
AB  - RATIONALE: Several studies have demonstrated a correlation between extracellular
      glutamate concentration in the mesolimbic reward pathway and alcohol craving.
      Extracellular glutamate concentration is regulated by several glutamate
      transporters. Glial glutamate transporter 1 (GLT1) is one of them that regulates
      the majority of extracellular glutamate concentration. In addition,
      cystine/glutamate antiporter (xCT) is another transporter that regulates
      extracellular glutamate. OBJECTIVES: We focus in this study to determine the
      effects of ceftriaxone, beta-lactam antibiotic, on glial proteins such as GLT1
      isoforms, xCT, glutamate aspartate transporter (GLAST), and several associated
      signaling pathways as well as ethanol intake in P rats. Additionally, to examine
      the onset of signaling pathways associated with GLT1 upregulation following
      ceftriaxone treatment, we tested 2- versus 5-day daily dosing of ceftriaxone.
      RESULTS: Ceftriaxone treatment (100 mg/kg), 2 and 5 days, resulted in about five
      fold reduction in ethanol intake by P rats. The reduction in ethanol intake was
      associated with significantly enhanced expression of GLT1, GLT1a, GLT1b, and xCT
      in the nucleus accumbens (NAc) and prefrontal cortex (PFC) of 5-day ceftriaxone
      treated P rats. Two-day-treated P rats showed marked changes in expression of
      these glutamate transporters in the PFC but not in the NAc. Importantly,
      ceftriaxone-treated P rats (2 and 5 days) demonstrated enhanced phosphorylation
      of Akt and nuclear translocation of nuclear factor kappaB (NFkappaB) in the NAc
      and PFC compared to control animals. CONCLUSIONS: These findings demonstrate that
      ceftriaxone treatment induced upregulation of GLT1, GLT1 isoforms, and xCT in
      association with activation of the Akt-NFkappaB signaling pathway.

PMID- 25619884
TI  - In vivo bacterial imaging without engineering; A novel probe-based strategy
      facilitated by endogenous nitroreductase enzymes.
AB  - The feasibility of utilising bacteria as vectors for gene therapy is becoming
      increasingly recognised. This is primarily due to a number of intrinsic
      properties of bacteria such as their tumour targeting capabilities, their ability
      to carry large genetic or protein loads and the availability of well-established
      genetic engineering tools for a range of common lab strains. However, a number of
      issues relating to the use of bacteria as vectors for gene therapy need to be
      addressed in order for the field to progress. Amongst these is the need for the
      development of non-invasive detection/imaging systems for bacteria within a
      living host. In vivo optical imaging has advanced preclinical research greatly,
      and typically involves engineering of bacteria with genetic expression constructs
      for luminescence (e.g. the lux operon) or fluorescent proteins (GFP etc.). This
      requirement for genetic modification can be restrictive, where engineering is not
      experimentally appropriate or technologically feasible (e.g. due to lack of
      suitable engineering tools). We describe a novel strategy exploiting endogenous
      bacterial enzymatic activity to specifically activate an exogenously administered
      fluorescent imaging probe. The red shifted, quenched fluorophore CytoCy5S is
      reduced to a fluorescent form by bacterial-specific nitroreductase (NTR) enzymes.
      NTR enzymes are present in a wide range of bacterial genera and absent in
      mammalian systems, permitting highly specific detection of Gram-negative and Gram
      positive bacteria in vivo. In this study, dose-responsive bacterial-specific
      signals were observed in vitro from all genera examined - E. coli, Salmonella,
      Listeria, Bifidobacterium and Clostridium difficile. Examination of an NTR
      knockout strain validated the enzyme specificity of the probe. In vivo whole-body
      imaging permitted specific, dose-responsive monitoring of bacteria over time in
      various infection models, and no toxicity to bacteria or host was observed. This
      study demonstrates the concept of exploiting innate NTR activity as a reporting
      strategy for wild-type bacteria using optical imaging, while the concept may also
      be extended to NTR-specific probes for use with other imaging modalities.

PMID- 25619885
TI  - Symptomatic improvement, increased life-span and sustained cell homing in
      amyotrophic lateral sclerosis after transplantation of human umbilical cord blood
      cells genetically modified with adeno-viral vectors expressing a neuro-protective
      factor and a neural cell adhesion molecule.
AB  - Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro
      degenerative disease characterized by progressive loss of moto-neurons and
      paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest
      investigation utilizing various approaches. Here we present an innovative gene
      cell construct aimed at reviving inert structure and function. Human umbilical
      cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human
      VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models.
      Significant improvement in behavioral performance (open-field and grip-strength
      tests), as well as increased life-span was observed in rodents treated with NCAM
      VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in
      the spinal cord of ALS mice 10 weeks after delivering genetically modified
      hUCBCs, and cells were detectable even 5 months following transplantation. Our
      gene-cell therapy model yielded prominent symptomatic control and prolonged life
      time in ALS. Incredible survivability of xeno-transpanted cells was also observed
      without any immune-suppression. These results suggest that engineered hUCBCs may
      offer effective gene-cell therapy in ALS.

PMID- 25619886
TI  - The sleeping beauty transposon vector system for treatment of rare genetic
      diseases: an unrealized hope?
AB  - Rare genetic diseases account for a considerable amount of fatalities and even
      their 'mild' or 'non-lethal' forms can produce drastic and undesirable discomfort
      to affected individuals. Various gene therapeutic approaches were tested for
      developing novel therapeutic concepts to treat these genetic diseases. Sleeping
      Beauty (SB) transposase represents one of these gene therapeutic systems which
      can be utilized for stable phenotypic correction. It is a transposable element
      which was resurrected and optimized for transposing genetic elements resulting in
      somatic integration of the transgene. Because of its versatile activity in many
      different organs, SB transposase has been explored for ex-vivo gene delivery and
      in vivo gene delivery including recently launched clinical trials based on
      engineered T-cells for tumor therapy and approaches to treat retinal
      degenerations. Here we will provide a state-of-the-art overview of preclinical
      studies for treatment of rare genetic diseases based on the SB transposase system
      for stable correction of the genetic defect. In this review, diseases affecting
      the blood system, the connective tissue, the immune system, the metabolism, and
      the nervous system and their treatment utilizing the SB transposase system will
      be discussed. Moreover, advantages and disadvantages of SB transposase-based gene
      therapeutic approaches will be mentioned. Although improvements of the SB
      transposase systems regarding genotoxicity and efficient delivery especially for
      applications in large mammals are desirable, the SB transposase system remains to
      hold great promise for curing rare genetic disease.

PMID- 25619887
TI  - Novel self-inactivating vectors for reconstitution of Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is a life-threatening disorder characterized by
      immunodeficiency, thrombocytopenia and eczema. Hematopoietic stem cell gene
      therapy can cure WAS but remains associated with the risk of leukemogenesis. In
      an effort to decrease the risk of gene-therapy induced leukemia associated with
      the use of first generation gamma-retroviral vectors, we have developed a series
      of codon-optimized WASP-expressing alpha-, gammaretro- and lentiviral self
      inactivating vectors and have performed comparative studies with regard to
      expression, vector dose and genotoxicity in vitro. In comparison to the
      conventional LTR-driven gammaretroviral vector, the self-inactivating (SIN)
      Elongation Factor 1 short form (EFS) - driven vectors presented decreased
      expression potency per vector copy. However, the safety profile of SIN vectors
      was superior, as evidenced by decreased genotoxicity in a murine hematopoietic
      progenitor cell - based in vitro immortalization assay. Using an in vitro OP9
      stroma cell - based co-culture system, we provide evidence that a codon-optimized
      lentiviral vector improves the B-cell differentiation block characteristic of
      WAS. Taken together, our studies represent a further step towards the development
      of a novel codon-optimized coWASP SIN vector for ex-vivo HSC gene therapy for
      Wiskott-Aldrich syndrome.

PMID- 25619888
TI  - Endoglin silencing has significant antitumor effect on murine mammary
      adenocarcinoma mediated by vascular targeted effect.
AB  - New targets and therapeutic approaches for vascular targeted strategies in
      oncology are continuously explored. Endoglin, a co-receptor of TGF-beta, is a
      known target, however, its silencing with vector-based RNA interference
      technology has not been evaluated yet. Therefore, in our study, we assembled
      plasmid DNA coding for shRNA against endoglin, and used gene electrotransfer as a
      delivery method to determine its antitumor and vascular targeted effects. In
      vitro and in vivo data provide evidence of vascular targeted effects of endoglin
      silencing. The vascular targeted action of endoglin silencing could be described
      as a result of two separated effect; antiangiogenic and vascular disrupting
      effect. This was first supported by in vitro data; predominantly by reduction of
      proliferation and tube formation of endothelial cells. In the TS/A murine mammary
      carcinoma model, in which the tumor cells do not express endoglin, reduced tumor
      growth and number of vessels were observed. Quick destruction of existing
      activated blood vessels at the site of tumor cells' injection and sustained
      growth of tumors afterwards was observed in tumors that were growing in dorsal
      window chamber by intravital microscopy. This observation supports both vascular
      disrupting and antiangiogenic action. In conclusion, the results of our study
      provide evidence of endoglin as a valid target for cancer therapy and support
      further development of plasmid shRNA delivery, which have prolonged antitumor
      effect, especially in combined schedules.

PMID- 25619889
TI  - Foxf1 siRNA delivery to hepatic stellate cells by DBTC lipoplex formulations
      ameliorates fibrosis in livers of bile duct ligated mice.
AB  - Activation of hepatic stellate cells (HSCs) is a key event in pathogenesis of
      liver fibrosis and represents an orchestral interplay of inhibiting and
      activating transcription factors like forkhead box f1 (Foxf1), being described to
      stimulate pro-fibrogenic genes in HSCs. Here, we evaluated a lipidbased liver
      specific delivery system (DBTC) suitable to transfer Foxf1 siRNA specifically to
      HSCs and examined its antifibrotic potential on primary HSCs and LX-2 cells as
      well as in a murine model of bile duct ligation (BDL)-induced secondary
      cholestasis. Foxf1 silencing reduced proliferation capacity and attenuated
      contractility of HSCs. Systemic administration of DBTC-lipoplexes in mice was
      sufficient to specifically silence genes expressed in different liver cell types.
      Using intravital and immunofluorescence microscopy we confirmed the specific
      delivery of Cy3-labeled DBTC to the liver, and particularly to HSCs. Repeated
      treatment with DBTC-lipoplexes resulted in siRNA-mediated silencing of Foxf1
      early after BDL and finally attenuated progression of the fibrotic process.
      Decreased HSC activation in-effect ameliorated liver injury as shown by
      substantial reduction of necrotic area and deposition of extracellular matrix.
      Our findings suggest that Foxf1 may serve as a target gene to disrupt progression
      of liver fibrosis and DBTC might provide a potentially feasible and effective
      tool for HSC-specific delivery of therapeutic RNA.

PMID- 25619890
TI  - Pentacene on Ni(111): room-temperature molecular packing and temperature
      activated conversion to graphene.
AB  - We investigate, using scanning tunnelling microscopy, the adsorption of pentacene
      on Ni(111) at room temperature and the behaviour of these monolayer films with
      annealing up to 700  degrees C. We observe the conversion of pentacene into
      graphene, which begins from as low as 220  degrees C with the coalescence of
      pentacene molecules into large planar aggregates. Then, by annealing at 350 
      degrees C for 20 minutes, these aggregates expand into irregular domains of
      graphene tens of nanometers in size. On surfaces where graphene and nickel
      carbide coexist, pentacene shows preferential adsorption on the nickel carbide
      phase. The same pentacene to graphene transformation was also achieved on
      Cu(111), but at a higher activation temperature, producing large graphene domains
      that exhibit a range of moire superlattice periodicities. 

PMID- 25619892
TI  - Structure determination of [Au18(SR)14].
AB  - Unravelling the atomic structures of small gold clusters is the key to
      understanding the origin of metallic bonds and the nucleation of clusters from
      organometallic precursors. Herein we report the X-ray crystal structure of a
      charge-neutral [Au18(SC6H11)14] cluster. This structure exhibits an unprecedented
      bi-octahedral (or hexagonal close packing) Au9 kernel protected by staple-like
      motifs including one tetramer, one dimer, and three monomers. Until the present,
      the [Au18(SC6H11)14] cluster is the smallest crystallographically characterized
      gold cluster protected by thiolates and provides important insight into the
      structural evolution with size. Theoretical calculations indicate charge transfer
      from surface to kernel for the HOMO-LUMO transition.

PMID- 25619893
TI  - Branching cascades provide access to two amino-oxazoline compound libraries.
AB  - An efficient synthetic access to two amino-oxazoline compound libraries was
      developed employing the branching cascades approach. A common precursor, that is,
      chromonylidene beta-ketoester was transformed into two different ring-systems,
      that is, the pyridine and the benzopyrane substituted hydroxyphenones. In further
      two steps, the ketone moiety in two ring-systems was transformed into an amino
      oxazoline ring. The functional groups on the two amino-oxazoline scaffolds were
      exploited further to generate, a compound collection of ca. 600 amino-oxazolines
      which are being exposed to various biological screenings within the European Lead
      Factory consortium. 

PMID- 25619891
TI  - Determination of the posterior boundary of Wernicke's area based on multimodal
      connectivity profiles.
AB  - Wernicke's area is one of the most important language regions and has been widely
      studied in both basic research and clinical neurology. However, its exact anatomy
      has been controversial. In this study, we proposed to address the anatomy of
      Wernicke's area by investigating different connectivity profiles. First, the
      posterior superior temporal gyrus (STG), traditionally called "Wernicke's area",
      was parcellated into three component subregions with diffusion MRI. Then, whole
      brain anatomical connectivity, resting-state functional connectivity (RSFC) and
      meta-analytic connectivity modeling (MACM) analyses were used to establish the
      anatomical, resting-state and task-related coactivation network of each subregion
      to identify which subregions participated in the language network. In addition,
      behavioral domain analysis, meta-analyses of semantics, execution speech, and
      phonology and intraoperative electrical stimulation were used to determine which
      subregions were involved in language processing. Anatomical connectivity, RSFC
      and MACM analyses consistently identified that the two anterior subregions in the
      posterior STG primarily participated in the language network, whereas the most
      posterior subregion in the temporoparietal junction area primarily participated
      in the default mode network. Moreover, the behavioral domain analyses, meta
      analyses of semantics, execution speech and phonology and intraoperative
      electrical stimulation mapping also confirmed that only the two anterior
      subregions were involved in language processing, whereas the most posterior
      subregion primarily participated in social cognition. Our findings revealed a
      convergent posterior anatomical border for Wernicke's area and indicated that the
      brain's functional subregions can be identified on the basis of its specific
      structural and functional connectivity patterns.

PMID- 25619894
TI  - Synthesis and anticancer cell potential of steroidal 16,17-seco-16,17a
      dinitriles: identification of a selective inhibitor of hormone-independent breast
      cancer cells.
AB  - We report the synthesis of steroidal 16,17-seco-16,17a-dinitriles and investigate
      their antitumor cell properties. Compounds were evaluated for anticancer
      potential by in vitro antiproliferation studies, molecular docking and virtual
      screening. Several compounds inhibit the growth of breast and prostate cancer
      cell lines (MCF-7, MDA-MB-231 and PC3), and/or cervical cancer cells (HeLa).
      Supporting this, molecular docking predicts that steroidal 16,17-seco-16,17a
      dinitriles could bind with high affinity to multiple molecular targets of breast
      and prostate cancer treatment (aromatase, estrogen receptor alpha, androgen
      receptor and 17alpha-hydroxylase) facilitated by D-seco flexibility and nitrile
      mediated contacts. Thus, 16,17-seco-16,17a-dinitriles may be useful for the
      design of inhibitors of multiple steroidogenesis pathways. Strikingly, 10, a 1,4
      dien-3-on derivative, displayed selective submicromolar antiproliferative
      activity against hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast
      cancer cells (IC50 0.52, 0.11MUM, respectively). Ligand-based 3D similarity
      searches suggest AKR1C, 17beta-HSD and/or 3beta-HSD subfamilies as responsible
      for this antiproliferative activity, while fast molecular docking identified
      AKR1C and ERbeta as potential binders-both targets in the treatment of hormone
      independent breast cancers. 

PMID- 25619895
TI  - Light-modulated seminal wavy roots in rice mediated by nitric oxide-dependent
      signaling.
AB  - Rice (Oryza sativa L.) seminal roots from germinated seeds help establish
      seedlings, but the seminal root growth and morphology are sensitive to
      environmental factors. Our previous research showed that several indica-type rice
      varieties such as Taichung native 1 (TCN1) showed light-induced wavy roots. Also,
      auxin and oxylipins are two signaling factors regulating the wavy root
      photomorphology. To investigate the signaling pathway, here, we found that nitric
      oxide (NO) was a second messenger triggering the signal transduction of light
      stimuli to induce the wavy morphology of seminal roots in rice. Moreover,
      interactions between oxylipins and phytohormones such as ethylene and auxin
      participating in the NO-dependent regulatory pathway of light-induced wavy roots
      were examined. The order of action of signaling components in the pathway was NO,
      oxylipins, ethylene, and auxin. 

PMID- 25619896
TI  - Laboratory challenges in primary aldosteronism screening and diagnosis.
AB  - BACKGROUND AND OBJECTIVE: The laboratory has a critical role to play in the
      screening and diagnosis of primary aldosteronism. This review highlights some of
      the important analytical considerations and the new developments in the
      determination of aldosterone and renin. METHODS: The review considered the
      published literature and clinical practice guidelines in the area of primary
      aldosteronism. RESULTS: A brief introduction to primary aldosteronism is
      provided. A detailed description of the pre-analytical, analytical and post
      analytical considerations for the laboratory determination of aldosterone, renin
      and the aldosterone to renin ratio follows. CONCLUSIONS: The lack of
      internationally accepted standardized methodologies and standard reference
      material has impeded screening and diagnosis of primary aldosteronism. The
      development of more accurate and sensitive methods by LC-MS/MS has improved the
      reliability of aldosterone and renin testing and the availability of commercial
      chemiluminescent assays may improve the standardization of reporting.
      Laboratorians need to understand the strengths and weaknesses of their analytical
      approach and ensure that their interpretative reports are appropriate to their
      assays.

PMID- 25619897
TI  - Rough-and-tumble play as a window on animal communication.
AB  - Rough-and-tumble play (RT) is a widespread phenomenon in mammals. Since it
      involves competition, whereby one animal attempts to gain advantage over another,
      RT runs the risk of escalation to serious fighting. Competition is typically
      curtailed by some degree of cooperation and different signals help negotiate
      potential mishaps during RT. This review provides a framework for such signals,
      showing that they range along two dimensions: one from signals borrowed from
      other functional contexts to those that are unique to play, and the other from
      purely emotional expressions to highly cognitive (intentional) constructions.
      Some animal taxa have exaggerated the emotional and cognitive interplay aspects
      of play signals, yielding admixtures of communication that have led to complex
      forms of RT. This complexity has been further exaggerated in some lineages by the
      development of specific novel gestures that can be used to negotiate playful mood
      and entice reluctant partners. Play-derived gestures may provide new mechanisms
      by which more sophisticated communication forms can evolve. Therefore, RT and
      playful communication provide a window into the study of social cognition,
      emotional regulation and the evolution of communication systems. 

PMID- 25619898
TI  - Automated red blood cell exchange for acute drug removal in a patient with
      sirolimus toxicity.
AB  - Sirolimus is an immunosuppressant used to prevent graft versus host disease in
      allogeneic hematopoietic stem cell transplant recipients. It has a large volume
      of distribution (12 +/- 7.5 l/kg) and within the intravascular space ~95% of it
      is bound to red blood cells. Because of potential toxic effects at high trough
      levels, therapeutic drug monitoring is recommended for sirolimus. We present a
      case of severe hepatic dysfunction due to Hepatitis B and sirolimus toxicity, in
      a 51-year-old male stem cell transplant recipient. An automated red cell exchange
      decreased his blood sirolimus level from 22.6 to 10.3 ng/ml (55% reduction) and
      improved his liver enzymes. Re-equilibration of sirolimus from other compartments
      to the blood necessitated a series of four red cell exchanges, after which the
      sirolimus level was 4.7 ng/ml. Although the patient ultimately succumbed to
      multiorgan failure, red cell exchange may be considered for acute removal of
      sirolimus in selected patients.

PMID- 25619899
TI  - Towards a quantitative model of kidney morphogenesis.
AB  - Kidney growth is dependent on functional interactions between mesenchymal nephron
      progenitors, the ureteric epithelium and surrounding stroma, which together make
      up the nephrogenic niche. Signalling between these populations regulates nephron
      progenitor maintenance, branching morphogenesis and nephron induction. Nephron
      endowment is sensitive to changes in the size of the nephron progenitor pool and
      to decreases in factors that promote branching morphogenesis. However,
      determining the morphogenic consequences of these disruptions in vivo has been
      challenging as quantitating kidney morphogenesis is hampered by the size, opacity
      and three-dimensional complexity of the tissue. The recent application of whole
      mount immunofluorescence and tissue clearing, coupled with multiscale imaging and
      quantitative analysis, has begun to give insights into the dynamics of kidney
      formation. This review focuses on how the quantitative nature of this approach
      has enabled mathematical modelling of cell cycle lengths, growth rates, cell
      number and branching rates and is advancing our understanding of kidney
      organogenesis. 

PMID- 25619901
TI  - [Stimulated urinary copper excretion in the diagnosis of Wilson's disease].

PMID- 25619902
TI  - [Chemical proctitis due to ergotamine: "not always an ulcerative colitis"].

PMID- 25619900
TI  - Manganese superoxide dismutase is required to maintain osteoclast differentiation
      and function under static force.
AB  - Bone homeostasis is maintained by the balance of osteoblasts (OBs) and
      osteoclasts (OCs). Increased activity of OCs not only contributes to pathological
      bone resorption, such as osteoporosis and periodontitis, but also is responsible
      for physiological conditions like orthodontic tooth movement (OTM). However, the
      detailed mechanism by which orthodontic force promotes the formation of OCs is
      still poorly understood. In this study, we confirmed that static force promoted
      the differentiation of human cord monocytes (HMNCs) into OCs depending on loading
      time and magnitude. Protein expression profiles among HMNCs, HMNCs subjected to
      static force and mature OCs were established via 2-DE and MALDI-TOF-MS analyses.
      Total respective protein spot numbers of 549 +/- 13, 612 +/- 19 and 634 +/- 16
      were detected in each of the gels by image analysis. The five proteins identified
      were plasminogen activator inhibitor 2 (PAI-2, Spot 1), peroxiredoxin-6 (PRD-6,
      Spot 3), manganese superoxide dismutase (SOD2, Spot 6), Rho GDP-dissociation
      inhibitor 2 (Rho-GDI2, Spot 11) and L-lactate dehydrogenase B chain (L-LDH, Spot
      15). More importantly, we revealed that SOD2 was required to maintain monocyte
      differentiation into functional OCs and may become a potential target for
      regulating the efficiency of OTM in the future. 

PMID- 25619903
TI  - [Vedolizumab in the treatment of Crohn's disease].
AB  - The anti-TNFalpha agents, infliximab and adalimumab, are effective in the
      treatment of Crohn's disease. Nevertheless, approximately one-third of patients
      do not initially respond to treatment and a substantial proportion experience
      loss of efficacy or intolerance to these drugs. Therefore, new drugs are
      obviously required, aimed at therapeutic targets other than TNFalpha. Notable
      among the therapeutic alternatives are drugs targeting integrins. Vedolizumab is
      a humanized monoclonal antibody that binds specifically to the alpha4beta7
      integrin, inhibiting T lymphocytes from binding to adhesion molecules (MAdCAM-1),
      which are expressed mainly in the small bowel and colon. Consequently, and unlike
      natalizumab, vedolizumab can be considered a specific intestinal
      immunosuppressant, making it especially attractive. The present article reviews
      the role of vedolizumab in Crohn's disease, paying special attention to its
      pharmacokinetic/pharmacodynamic properties, indications, effectiveness, and
      safety. 

PMID- 25619904
TI  - The Role of Potassium Channels in the Vasodilatation Induced by Resveratrol and
      Naringenin in Isolated Human Umbilical Vein.
AB  - Preclinical Research Potassium (K+ ) channels have a key role in the maintenance
      of smooth muscle tone; a variety of agonists can modify the tone by altering K+ 
      channel activity. The aim of this study was assess the effects of the phenols,
      resveratrol, and naringenin on K+ -channels of the vascular smooth muscle.
      Segments of human umbilical vein (HUV) without endothelium were precontracted
      using serotonin (100 MUM) or 100 mM K+ to derive cumulative concentration
      response curves using increasing concentrations of resveratrol or naringenin. K+ 
      channel inhibitors were added in the bath before resveratrol (1-100 MUM) or
      naringenin (0.01-1 mM) in assess the role of K+ -channels in their effects on HUV
      precontracted by serotonin. 4-Aminopiridine (4-AP; 1 mM), a nonselective blocker
      of voltage-dependent, tetraethylammonium (TEA; 1 mM) and barium chloride (1 mM),
      a nonselective blocker of Ca2+ -dependent and inward rectifier K+ -channels
      (respectively) induced significant shifts to the right (P < 0.05) of resveratrol.
      concentration-response curves. The effect of naringenin was antagonized by 4-AP
      (1 mM). 4-AP-, TEA-, and barium chloride-sensitive K+ -channels are probably
      involved in the resveratrol vasodilatatory effect, while naringenin seems to
      affect 4-AP-sensitive K+ -channels. However, other mechanisms of vasodilation
      induced by polyphenols could not be excluded. Drug Dev Res, 2015. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25619905
TI  - An effective method, composed of LAMP and dCAPS, to detect different mutations in
      fenoxaprop-P-ethyl-resistant American sloughgrass (Beckmannia syzigachne Steud.)
      populations.
AB  - The decreased susceptibility of Beckmannia syzigachne to fenoxaprop-P-ethyl is
      due to the reliance on it to control grass weeds since the 1990s. Loop-mediated
      isothermal amplification (LAMP), which is a proven simple, rapid, specific,
      sensitive and inexpensive assay method, has been used to detect the I1781L
      mutation in B. syzigachne. In the present study, four sets of primers detected
      four mutations in B. syzigachne, W2027C, I2041A, D2078G and G2096A, using the
      LAMP method. Additionally, five newly derived cleaved amplified polymorphic
      sequence (dCAPS) markers were developed to detect five different mutations. With
      a method composed of LAMP and dCAPS, 19 fenoxaprop-P-ethyl-resistant B.
      syzigachne populations collected in 2013 were studied. An effective method,
      composed of LAMP and dCAPS, to detect five mutations, I1781L, W2027C, I2041A,
      D2078G and G2096A, in B. syzigachne populations was developed. With this method,
      a B. syzigachne population resistant to fenoxaprop-P-ethyl can be studied to
      confirm its constitution. And we determined that the resistance level might be
      relevant to the mutation type and mutation frequency. The type of mutation and
      its frequency in fenoxaprop-P-ethyl-resistant B. syzigachne populations can be
      confirmed to provide appropriate herbicide management. 

PMID- 25619906
TI  - Triazophos-induced oxidative stress and histomorphological changes in ovary of
      female Wistar rats.
AB  - Triazophos (TZ), a non-systemic broad spectrum organophosphate (OP), is being
      extensively used against a wide range of pests in agricultural practices. The
      present study was carried out to investigate the toxic effects of triazophos (TZ)
      in female Wistar rats. Three sub-chronic dose levels of TZ corresponding to
      1/10th, 1/20th and 1/40th of LD50 were given for 30 days to adult female Wistar
      rats through oral intubation. During the treatment period estrous cycle was
      significantly altered. Activity levels of different oxidative stress (OS)
      parameters viz. catalase (CAT), superoxide dismutase (SOD), glutathione-S
      transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and
      lipid peroxidation (LPO) were differentially altered in the ovary of treated
      rats. Estradiol levels were significantly high while progesterone levels were
      significantly reduced in plasma of 1/10th and 1/20th of LD50 TZ-treated rats.
      Histomorphological studies of ovary revealed increased follicular atresia and
      increased ovarian surface epithelial height in 1/10th and 1/20th of LD50 TZ
      treated rats. Enhanced apoptosis and necrosis were also observed in ovarian
      granulosa cells at dose-dependent manner. Results infer that TZ exposure may lead
      to the number of pathophysiological conditions in female rats and severity
      increases at high doses.

PMID- 25619907
TI  - Physiological and biochemical characteristics of laboratory induced mutants of
      Botrytis cinerea with resistance to fluazinam.
AB  - Botrytis cinerea is a necrotrophic and filamentous fungus with a high risk of
      developing resistance to fungicides. The pyridinamine fungicide fluazinam has
      been reported to have excellent activity against B. cinerea and better effect on
      controlling gray mold. In this study, the physiological and biochemical
      characteristics of laboratory-induced mutants of B. cinerea with resistance to
      fluazinam has been investigated. Compared to the wild-type strains, the fluazinam
      resistant mutants had a significant decrease in respiratory rate, glycerol,
      oxalate, and ATP contents, and an increase in ATPase activity and sensitivity to
      osmotic pressure, but did not differ in cell membrane permeability. Sequencing
      indicated that two parental strains and four resistant mutants were identical in
      the nucleotide sequence of F-ATPase gene. These results will enrich our
      understanding of the resistance mechanism of B. cinerea to fluazinam. 

PMID- 25619908
TI  - Tolerance of ARPE 19 cells to organophosphorus pesticide chlorpyrifos is limited
      to concentration and time of exposure.
AB  - Age related macular degeneration is a blinding disease common in elder adults.
      The prevalence of age related macular degeneration has been found to be 1.8% in
      the Indian population. Organophosphates are widely used insecticides with well
      documented neurological effects, and the persistent nature of these compounds in
      the body results in long term health effects. Farmers exposed to organophosphorus
      pesticides in USA had an earlier onset of age related macular degeneration when
      compared to unexposed controls. A recent study found significant levels of an
      organophosphate, termed chlorpyrifos, in the blood samples of Indian farmers.
      Therefore, in understanding the link between age related macular degeneration and
      chlorpyrifos, the need for investigation is important. Our data show that ARPE-19
      (retinal pigment epithelial cells) exhibit a cytoprotective response to
      chlorpyrifos as measured by viability, mitochondrial membrane potential,
      superoxide dismutase activity, and increased levels of glutathione peroxidase and
      reduced glutathione, after 24 h exposure to chlorpyrifos. However, this
      cytoprotective response was absent in ARPE-19 cells exposed to the same range of
      concentrations of chlorpyrifos for 48 h. These results have physiological
      significance, since HPLC analysis showed that effects of chlorpyrifos were
      mediated through its entry into ARPE-19 cells. HPLC analysis also showed that
      chlorpyrifos remained stable, as we recovered up to 80% of the chlorpyrifos added
      to 6 different ocular tissues.

PMID- 25619909
TI  - A novel Pro197Glu substitution in acetolactate synthase (ALS) confers broad
      spectrum resistance across ALS inhibitors.
AB  - Water chickweed (Myosoton aquaticum L.), a competitive broadleaf weed, is
      widespread in wheat fields in China. Tribenuron and pyroxsulam failed to control
      water chickweed in the same field in Qiaotian Village in 2011 and 2012,
      respectively. An initial tribenuron resistance confirmation test identified a
      resistant population (AH02). ALS gene sequencing revealed a previously unreported
      substitution of Glu for Pro at amino acid position 197 in resistant individuals.
      A purified subpopulation (WRR04) that was individually homozygous for the
      Pro197Glu substitution was generated and characterized in terms of its response
      to different classes of ALS inhibitors. A whole-plant experiment showed that the
      WRR04 population exhibited broad-spectrum resistance to tribenuron (SU, 318
      fold), pyrithiobac sodium (PTB, > 197-fold), pyroxsulam (TP, 81-fold), florasulam
      (TP, > 36-fold) and imazethapyr (IMI, 11-fold). An in vitro ALS assay confirmed
      that the ALS from WRR04 showed high resistance to all the tested ALS inhibitors.
      These results established that the Pro197Glu substitution endows broad-spectrum
      resistance across ALS inhibitors in water chickweed. In addition, molecular
      markers were developed to rapidly identify the Pro197Glu mutation.

PMID- 25619910
TI  - Effects of phenazine-1-carboxylic acid on the biology of the plant-pathogenic
      bacterium Xanthomonas oryzae pv. oryzae.
AB  - Xanthomonas oryzae pv. oryzae (Xoo) is the casual agent of bacterial blight,
      which is one of the most serious diseases of rice. The antibiotic phenazine-1
      carboxylic acid (PCA), which is primarily produced by Pseudomonas spp., was found
      and previously reported very effective against Xoo. However, the biological
      effects of PCA on Xoo remain unclear. In this study, we found that PCA increased
      the accumulation of reactive oxygen species (ROS) and reduced the activities of
      catalase (CAT) and superoxide dismutase (SOD) in Xoo. Xoo was more sensitive to
      H2O2 than Xanthomonas oryzae pv. oryzicola (Xoc), and had a much lower expression
      of CAT genes. In addition, proteomic analysis indicated that PCA inhibited
      carbohydrate metabolism and nutrient uptake in Xoo, and analysis of carbon source
      utilization further confirmed that carbohydrate metabolism in Xoo was repressed
      by PCA. In conclusion, PCA acted as a redox-cycling agent that disturbed the
      redox balance in Xoo and reduced CAT and SOD activities, resulting in higher
      accumulation of ROS, altered carbohydrate metabolism, and lower energy production
      and nutrient uptake. Moreover, a deficient antioxidant system in Xoo made it very
      sensitive to PCA. 

PMID- 25619911
TI  - Differentially expressed genes in the fat body of Bombyx mori in response to
      phoxim insecticide.
AB  - The silkworm, Bombyx mori, is an economically important insect. However,
      poisoning of silkworms by organophosphate pesticides causes tremendous loss to
      the sericulture. The fat body is the major tissue involved in detoxification and
      produces antimicrobial peptides and regulates hormones. In this study, a
      microarray system comprising 22,987 oligonucluotide 70-mer probes was employed to
      examine differentially expressed genes in the fat body of B. mori exposed to
      phoxim insecticide. The results showed that a total of 774 genes were
      differentially expressed upon phoxim exposure, including 500 up-regulated genes
      and 274 down-regulated genes. The expression levels of eight detoxification
      related genes were up-regulated upon phoxim exposure, including six cytochrome
      P450s and two glutathione-S-transferases. It was firstly found that eight
      antimicrobial peptide genes were down-regulated, which might provide important
      references for studying the larvae of B. mori become more susceptible to
      microbial infections after phoxim treatment. In addition, we firstly detected the
      expression level of metamorphosis-related genes after phoxim exposure, which may
      lead to impacted reproduction. Our results may facilitate the overall
      understanding of the molecular mechanism of multiple pathways following exposure
      to phoxim insecticide in the fat body of B. mori.

PMID- 25619912
TI  - Resistance selection and molecular mechanisms of cypermethrin resistance in red
      hairy caterpillar (Amsacta albistriga walker).
AB  - Amsacta albistriga is one of the important pests of oilseed crops in India. This
      pest has developed high resistance to organophosphate (OP) insecticide in field.
      Therefore, cypermethrin insecticide was used as an alternative for this pest.
      After 20 generations of selection with cypermethrin, the LD50 value for A.
      albistriga was increased by 21.5-folds. The synergism ratio of piperonyl butoxide
      (PBO) and triphenyl phosphate (TPP) was increased by 10- and 9.6-fold in
      resistant strains and comparatively, 3.9 and 4.2-fold in susceptible strains.
      Detoxification enzyme analysis and native PAGE electrophoresis of esterase
      isoenzyme further revealed that esterase and mixed function oxidase may be
      involved in cypermethrin resistance in CypRes strain. In addition to enzyme
      analysis overexpression of CYP4M44, CYP9A77 and CYP6B47 (ortholog) can confer
      metabolic resistance in the CypRes strain. These data provide a foundation for
      further study of cypermethrin resistance mechanism observed in A. albistriga. 

PMID- 25619913
TI  - Identification of polymorphisms in Cyrtorhinus lividipennis RDL subunit
      contributing to fipronil sensitivity.
AB  - As one of the most important predatory enemies, the miridbug, Cyrtorhinus
      lividipennis, plays an important role in rice planthoppers control, such as
      Nilaparvata lugens (brown planthopper). In order to compare insecticide
      selectivity between C. lividipennis and N. lugens, the contact acute toxicities
      of six insecticides (diazoxon, paraoxon, carbaryl, fenobucarb, fipronil and
      ethofenprox) were monitored. The results showed that all tested insecticides were
      more toxic to C. lividipennis than to N. lugens and fipronil had the biggest
      difference. The RDL subunit (Cl-RDL) was cloned from C. lividipennis and a RDL
      isoform (Cl-RDL-In) was also found with 31 amino acids insertion in RDL
      intracellular region. In order to understand the role of the insertion on
      insecticide sensitivities, three subunits (Nl-RDL, Cl-RDL and Cl-RDL-In) were
      constructed to obtain the functional receptors in Xenopus oocytes and the
      fipronil sensitivities were detected by the voltage-clamp technique. Nl-RDL
      (IC50=32.36 +/- 4.07 uM) was more insensitive to fipronil than Cl-RDL (IC50=6.47
      +/- 1.12 uM). The insertion in Cl-RDL significantly reduced fipronil sensitivity
      with IC50 value in Cl-RDL-In of 16.83 +/- 2.30 uM. Interestingly, after the
      elution of fipronil, the current response of Cl-RDL-In appeared obvious recovery,
      which were not observed in Cl-RDL and Nl-RDL. It might imply that the insertion
      played a special role in fipronil sensitivity.

PMID- 25619914
TI  - Tribenuron-methyl resistance and mutation diversity of Pro197 in flixweed
      (Descurainia Sophia L.) accessions from China.
AB  - Flixweed (Descurainia Sophia L.) is a problematic weed in winter wheat fields in
      China, which causes great loss of wheat yield. A total of 46 flixweed accessions
      from winter wheat-planting areas were collected and used for the survey of
      resistance to tribenuron-methyl and Pro197 mutation diversity. According to the
      "R" resistance rating system, 16 flixweed accessions have evolved resistance to
      tribenuron-methyl, 13 accessions have high risk of developing resistance to this
      herbicide and 17 accessions are susceptible. The mutation of Pro197 codon (CCT)
      changed proline (Pro) into leucine (Leu) (homozygous, RR), serine (Ser, RR),
      histidine (His, RR), threonine (Thr, RR), Pro/Leu (heterozygous, RS), Pro/Ser
      (RS), Pro/His, Pro/Thr (RS) and Pro/Tyr (RS). Among these amino acid changes, a
      Pro197-Pro/Tyr (heterozygous, RS) substitution caused by the mutation of two
      successive nucleotides was identified for the first time in resistant weed
      species. In addition, the Pro197-His and Pro197-Pro/His mutations have not been
      reported previously in flixweed. Finally, a CPAS marker was developed to identify
      flixweed plants with or without Pro197 mutation. 

PMID- 25619915
TI  - NF023 binding to XIAP-BIR1: searching drugs for regulation of the NF-kappaB
      pathway.
AB  - Inhibitor of Apoptosis Proteins (IAPs) are the target of extensive research in
      the field of cancer therapy since they regulate apoptosis and cell survival. Smac
      mimetics, the most promising IAP-targeting compounds specifically recognize the
      IAP-BIR3 domain and promote apoptosis, competing with caspases for IAP binding.
      Furthermore, Smac-mimetics interfere with the NF-kappaB survival pathway,
      inducing cIAP1 and cIAP2 degradation through an auto-ubiquitination process. It
      has been shown that the XIAP-BIR1 (X-BIR1) domain is involved in the interaction
      with TAB1, an upstream adaptor for TAK1 kinase activation, which in turn couples
      with the NF-kappaB survival pathway. Preventing X-BIR1 dimerization abolishes
      XIAP-mediated NF-kappaB activation, thus implicating a proximity-induced
      mechanism for TAK1 activation. In this context, in a systematic search for a
      molecule capable of impairing X-BIR1/TAB1 assembly, we identified the compound
      NF023. Here we report the crystal structure of the human X-BIR1 domain in the
      absence and in the presence of NF023, as a starting concept for the design of
      novel BIR1-specific compounds acting synergistically with existing pro-apoptotic
      drugs in cancer therapy.

PMID- 25619916
TI  - Cutaneous carcinosarcoma and the EMT: to transition, or not to transition? That
      is the question.

PMID- 25619917
TI  - Pediatricians' responses to printed clinical reminders: does highlighting prompts
      improve responsiveness?
AB  - OBJECTIVE: Physicians typically respond to roughly half of the clinical decision
      support prompts they receive. This study was designed to test the hypothesis that
      selectively highlighting prompts in yellow would improve physicians'
      responsiveness. METHODS: We conducted a randomized controlled trial using the
      Child Health Improvement Through Computer Automation clinical decision support
      system in 4 urban primary care pediatric clinics. Half of a set of electronic
      prompts of interest was highlighted in yellow when presented to physicians in 2
      clinics. The other half of the prompts was highlighted when presented to
      physicians in the other 2 clinics. Analyses compared physician responsiveness to
      the 2 randomized sets of prompts: highlighted versus not highlighted.
      Additionally, several prompts deemed high priority were highlighted during the
      entire study period in all clinics. Physician response rates to the high-priority
      highlighted prompts were compared to response rates for those prompts from the
      year before the study period, when they were not highlighted. RESULTS: Physicians
      did not respond to prompts that were highlighted at higher rates than prompts
      that were not highlighted (62% and 61%, respectively; odds ratio 1.056, P = .259,
      NS). Similarly, physicians were no more likely to respond to high-priority
      prompts that were highlighted compared to the year before, when the prompts were
      not highlighted (59% and 59%, respectively, chi(2) = 0.067, P = .796, NS).
      CONCLUSIONS: Highlighting reminder prompts did not increase physicians'
      responsiveness. We provide possible explanations why highlighting did not improve
      responsiveness and offer alternative strategies to increasing physician
      responsiveness to prompts.

PMID- 25619918
TI  - Organic pollution in surficial sediments of Tripoli harbour, Lebanon.
AB  - Tripoli harbour is among the most important ports on the Mediterranean Sea
      eastern basin. The persistent organic pollutants (POPs) were monitored (28 PCBs,
      16 PAHs and 18 Me-PAHs) in 15 stations of Tripoli harbour basins, which are
      influenced by anthropogenic activities. Total PAHs concentrations ranged from 243
      to 2965 MUg kg(-1)dw, total Me-PAH concentrations ranged from 54 to 1638 MUg kg(
      1)dw, while total PCB levels ranged from 18 to 302 MUg kg(-1)dw. PCBs profiles
      were dominated by four and six-chlorinated congeners while the PAHs were
      dominated by four and five rings. For identifying pollution emission sources of
      PAHs, different ratios were used. The results show that the pollution origin was
      predominated by pyrogenic process related to the deposition of coal dust and the
      combustion of biomass and coal. Based on Sediments Quality Guidelines the
      biological adverse effects on aquatic ecosystems were expected rarely to
      occasionally for PAHs and PCBs contamination.

PMID- 25619919
TI  - Development of a model for robust and exploratory analysis of the rodent brief
      access taste aversion data.
AB  - The rodent brief-access taste aversion (BATA) model is an efficient in vivo
      screening tool for taste assessment. A new E(max) (maximum effect attributable to
      the drug) model was developed and further investigated in comparison with three
      previously published models for analysing the rodent BATA data; the robustness of
      all the models was discussed. The rodent BATA data were obtained from a series of
      experiments conducted with a bitter reference compound, quinine hydrochloride
      dihydrate (QHD). A new E(max) model that could be applied to both "lick numbers"
      and "lick ratios" was built and three published models that used lick ratios were
      employed for analysing the BATA data. IC50, the concentration that inhibits 50%
      of the maximum lick numbers, quantified the oral aversiveness of QHD. One
      thousand bootstrap datasets were generated from the original data. All models
      were applied to estimate the confidence intervals of the IC50s without symmetric
      assumption. The IC50 value obtained from the new E(max) model was 0.0496 mM (95%
      CI 0.0297-0.0857) using the lick numbers for analysis, while an IC50 of 0.0502 mM
      (95% CI 0.0267-0.0859) was acquired with the lick ratios. Except one published
      model, the IC50 values have a similar range for the 95% CI. The new E(max) model
      enabled the analysis of both "lick numbers" and "lick ratios" whereas other
      models could only handle data presented as "lick ratios". IC50s obtained with
      these two types of datasets showed similarity among all models thereby justified
      the robustness of the new E(max) model.

PMID- 25619920
TI  - Bromelain nanoparticles protect against 7,12-dimethylbenz[a]anthracene induced
      skin carcinogenesis in mouse model.
AB  - Conventional cancer chemotherapy leads to severe side effects, which limits its
      use. Nanoparticles (NPs) based delivery systems offer an effective alternative.
      Several evidences highlight the importance of Bromelain (BL), a proteolytic
      enzyme, as an anti-tumor agent which however has been limited due to the
      requirement of high doses at the tumor site. Therefore, we illustrate the
      development of BL loaded poly (lactic-co-glycolic acid) NPs that show enhanced
      anti-tumor effects compared to free BL. The formulated NPs with a mean particle
      size of 130.4 +/- 8.81 nm exhibited sustained release of BL. Subsequent
      investigation revealed enhanced anti-tumor ability of NPs in 2-stage skin
      tumorigenesis mice model. Reduction in average number of tumors (~ 2.3 folds),
      delay in tumorigenesis (~ 2 weeks), percent tumorigenesis (~ 4 folds), and
      percent mortality rate as well as a reduction in the average tumor volume (~ 2.5
      folds) in mice as compared to free BL were observed. The NPs were found to be
      superior in exerting chemopreventive effects over chemotherapeutic effects at 10
      fold reduced dose than free BL, validated by the enhanced ability of NPs (~ 1.8
      folds) to protect the DNA from induced damage. The effects were also supported by
      histopathological evaluations. NPs were also capable of modulating the expression
      of pro-apoptotic (P53, Bax) and anti-apoptotic (Bcl2) proteins. Therefore, our
      findings demonstrate that developed NPs formulation could be used to improve the
      efficacy of chemotherapy by exerting chemo-preventive effects against induced
      carcinogenesis at lower dosages.

PMID- 25619921
TI  - Differential effects of ambient or diminished CO2 and O2 levels on thylakoid
      membrane structure in light-stressed plants.
AB  - Over-reduction of the photosynthetic electron transport chain may severely damage
      the photosynthetic apparatus as well as other constituents of the chloroplast and
      the cell. Here, we exposed Arabidopsis leaves to saturating light either under
      normal atmospheric conditions or under CO2--and O2 -limiting conditions, which
      greatly increase excitation and electron pressures by draining terminal electron
      acceptors. The two treatments were found to have very different, often opposing,
      effects on the structure of the thylakoid membranes, including the width of the
      granal lumenal compartment. Modulation of the latter is proposed to be related to
      movements of ions across the thylakoid membrane, which alter the relative
      osmolarity of the lumen and stroma and affect the partitioning of the proton
      motive force into its electrical and osmotic components. The resulting changes in
      thylakoid organization and lumenal width should facilitate the repair of
      photodamaged photosystem II complexes in response to light stress under ambient
      conditions, but are expected to inhibit the repair cycle when the light stress
      occurs concurrently with CO2 and O2 depletion. Under the latter conditions, the
      changes in thylakoid structure are predicted to complement other processes that
      restrict the flow of electrons into the high-potential chain, thus moderating the
      production of deleterious reactive oxygen species at photosystem I.

PMID- 25619922
TI  - Beliefs of teachers versus non-teachers about people who stutter.
AB  - PURPOSE: Although prior research has investigated teachers' beliefs about people
      who stutter (PWS), this work has not indicated how these beliefs compare with
      those of the general public or taken into account key demographic variables that
      may be related to these beliefs. The main purpose of this study was to evaluate
      whether beliefs about PWS in teachers are different from those in the general
      public. The second purpose of this study was to examine whether gender is related
      to beliefs about PWS for teachers, who are more frequently women. METHODS:
      Analyses were based on questionnaire responses regarding beliefs about PWS from
      269 teachers and 1388 non-teachers in the United States. Due to their potential
      link to beliefs about PWS, familiarity with PWS and sociodemographic variables
      were included in the statistical model for this study. RESULTS: Teachers' beliefs
      about PWS are no different than those of people in non-teaching professions.
      Findings also indicated that, regardless of whether respondents were teachers,
      women had more accurate beliefs about PWS than men. The statistical model tested
      indicated that beliefs about PWS were more accurate when the respondents were
      older, had more education, and had familiarity with a PWS. CONCLUSION: In the
      first study to compare teachers' beliefs about PWS to the general public,
      findings indicated that teachers are no more accurate than the public in their
      beliefs about PWS. Associations found between these beliefs and several variables
      may indicate some promising mechanisms for improving beliefs, such as increased
      familiarity with individuals who stutter. EDUCATIONAL OBJECTIVES: Readers should
      be able to: (a) describe stuttering's potential effects on children's
      participation in the school setting; (b) identify actions teachers can take to
      improve the school experience of their students who stutter; (c) summarize
      findings regarding teachers' beliefs about people who stutter (PWS); (d) identify
      key variables that are associated with beliefs about PWS.

PMID- 25619923
TI  - Effects of preventive home visits by district nurses on self-reported health of
      75-year-olds.
AB  - AIM: The aim of this study was to analyse the effects of preventive home visits
      (PHVs) by district nurses (DNs) on the self-reported health of 75-year-olds,
      including changes in self-reported health after the visits. The study also
      investigated whether or not the participants believed the visit was useful.
      BACKGROUND: There is a need for methods that promote health among older persons
      so that they can remain healthy as long as possible. One such method is PHVs. In
      Sweden, the Stockholm County Council decided to implement such visits to 75-year
      olds. METHODS: The study was a cluster-controlled trial carried out in Stockholm.
      Sixteen healthcare centres (HCCs) were randomly selected from five geographic
      medical areas in the county. Eight were assigned to the study group (SG) and
      eight to the control group (CG). The 75-year-olds registered at these centres (SG
      n=176, CG n=262) filled in a questionnaire before and after the intervention.
      Each SG member received a PHV from a DN, and the CG was treated as usual.
      FINDINGS: At follow-up, both the groups reported decreased health and well-being.
      However, the SG reported a significant reduction in pain as an effect of the PHV.
      Participants in the SG reported increased knowledge of local community and county
      council services, more contacts with their HCCs and increased use of medication.
      The PHV had no effect on health behaviour. The CG reported significantly more
      problems in the categories of activities of daily living (ADL) and
      breathing/circulation. Eighty-four per cent of the participants reported that the
      PHV was somewhat useful, useful or very useful.

PMID- 25619924
TI  - Hypoxia-induced relaxation of porcine retinal arterioles in vitro depends on
      inducible NO synthase and EP4 receptor stimulation in the perivascular retina.
AB  - PURPOSE: Hypoxia-induced relaxation of porcine retinal arterioles has been shown
      to be reduced during inhibition of prostaglandin synthesis and nitric oxide
      synthase (NOS). The purpose of this study was to identity the specific
      prostaglandin receptor(s) and source(s) of NO mediating this effect. METHODS:
      Porcine retinal arterioles with preserved perivascular retinal tissue were
      mounted in a myograph and were exposed to hypoxia in the presence of one of the
      following: the general NO synthase inhibitor L-NAME, the selective iNOS inhibitor
      1400W, the selective nNOS inhibitor 7-nitroindazole, the general cyclooxygenase
      (COX) inhibitor ibuprofen or an antagonist to the FP- (AL 8810), DP- (BWA868C),
      EP1 - (SC-19220), EP2 - (PF-044189) or EP4 receptors (GW627368X). The experiments
      were repeated after removal of the perivascular retinal tissue. RESULTS: Hypoxia
      induced relaxation of retinal arterioles with preserved perivascular retinal
      tissue. This relaxation was significantly reduced in the presence of L-NAME,
      1400W, ibuprofen and the EP4 receptor antagonist GW627368X. The simultaneous
      addition of L-NAME or 1400W in combination with ibuprofen, but not GW627368X,
      reduced hypoxia-induced vasorelaxation additively as compared to the effect of
      the compounds individually. CONCLUSION: Hypoxia-induced vasorelaxation of porcine
      retinal arterioles is mediated by inducible NOS and stimulation of EP4 receptors
      acting through separate pathways, but mechanisms unrelated to the studied
      prostaglandin receptors and NOS products are also involved.

PMID- 25619925
TI  - Endocytosis of Hedgehog through dispatched regulates long-range signaling.
AB  - The proteins of the Hedgehog (Hh) family are secreted proteins exerting short-
      and long-range control over various cell fates in developmental patterning. The
      Hh gradient in Drosophila wing imaginal discs consists of apical and basolateral
      secreted pools, but the mechanisms governing the overall establishment of the
      gradient remain unclear. We investigated the relative contributions of
      endocytosis and recycling to control the Hh gradient. We show that, upon its
      initial apical secretion, Hh is re-internalized. We examined the effect of the
      resistance-nodulation-division transporter Dispatched (Disp) on long-range Hh
      signaling and unexpectedly found that Disp is specifically required for apical
      endocytosis of Hh. Re-internalized Hh is then regulated in a Rab5- and Rab4
      dependent manner to ensure its long-range activity. We propose that Hh-producing
      cells integrate endocytosis and recycling as two instrumental mechanisms
      contributing to regulate the long-range activity of Hh. 

PMID- 25619926
TI  - A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division.
AB  - Recent evidence suggests that endoplasmic reticulum (ER) tubules mark the sites
      where the GTPase Drp1 promotes mitochondrial fission via a largely unknown
      mechanism. Here, we show that the SNARE protein syntaxin 17 (Syn17) is present on
      raft-like structures of ER-mitochondria contact sites and promotes mitochondrial
      fission by determining Drp1 localization and activity. The hairpin-like C
      terminal hydrophobic domain, including Lys-254, but not the SNARE domain, is
      important for this regulation. Syn17 also regulates ER Ca(2+) homeostasis and
      interferes with Rab32-mediated regulation of mitochondrial dynamics. Starvation
      disrupts the Syn17-Drp1 interaction, thus favoring mitochondrial elongation
      during autophagy. Because we also demonstrate that Syn17 is an ancient SNARE, our
      findings suggest that Syn17 is one of the original key regulators for ER
      mitochondria contact sites present in the last eukaryotic common ancestor. As
      such, Syn17 acts as a switch that responds to nutrient conditions and integrates
      functions for the ER and autophagosomes with mitochondrial dynamics. 

PMID- 25619927
TI  - Mechanisms of Behavioral and Affective Treatment Outcomes in a Cognitive
      Behavioral Intervention for Boys.
AB  - Evidence for effective treatment for behavioral problems continues to grow, yet
      evidence about the effective mechanisms underlying those interventions has lagged
      behind. The Stop Now and Plan (SNAP) program is a multicomponent intervention for
      boys between 6 and 11. This study tested putative treatment mechanisms using data
      from 252 boys in a randomized controlled trial of SNAP versus treatment as usual.
      SNAP includes a 3 month group treatment period followed by individualized
      intervention, which persisted through the 15 month study period. Measures were
      administered in four waves: at baseline and at 3, 9 and 15 months after baseline.
      A hierarchical linear modeling strategy was used. SNAP was associated with
      improved problem-solving skills, prosocial behavior, emotion regulation skills,
      and reduced parental stress. Prosocial behavior, emotion regulation skills and
      reduced parental stress partially mediated improvements in child aggression.
      Improved emotion regulation skills partially mediated treatment-related child
      anxious-depressed outcomes. Improvements in parenting behaviors did not differ
      between treatment conditions. The results suggest that independent processes may
      drive affective and behavioral outcomes, with some specificity regarding the
      mechanisms related to differing treatment outcomes.

PMID- 25619928
TI  - Common Etiological Sources of Anxiety, Depression, and Somatic Complaints in
      Adolescents: A Multiple Rater twin Study.
AB  - Somatic complaints in children and adolescents may be considered part of a
      broader spectrum of internalizing disorders that include anxiety and depression.
      Previous research on the topic has focused mainly on the relationship between
      anxiety and depression without investigating how common somatic symptoms relate
      to an underlying factor and its etiology. Based on the classical twin design with
      monozygotic and dizygotic twins reared together, our study aimed to explore the
      extent to which the covariation between three phenotypes in adolescent girls and
      boys can be represented by a latent internalizing factor, with a focus on both
      common and specific etiological sources. A population-based sample of twins aged
      12-18 years and their mothers and fathers (N = 1394 families) responded to
      questionnaire items measuring the three phenotypes. Informants' ratings were
      collapsed using full information maximum likelihood estimated factor scores.
      Multivariate genetic analyses were conducted to examine the etiological structure
      of concurrent symptoms. The best fitting model was an ACE common pathway model
      without sex limitation and with one substantially heritable (44%) latent factor
      shared by the phenotypes. Concurrent symptoms also resulted from shared (25%) and
      non-shared (31%) environments. The factor loaded most on depression symptoms and
      least on somatic complaints. Trait-specific influences explained 44% of
      depression variance, 59% of anxiety variance, and 65% of somatic variance. Our
      results suggest the presence of a general internalizing factor along which
      somatic complaints and mental distress can be modeled. However, specific
      influences make the symptom types distinguishable.

PMID- 25619929
TI  - Preparation of a silver nanoparticle-based dual-functional sensor using a
      complexation-reduction method.
AB  - A dual-functional sensor based on silver nanoparticles was synthesized by a two
      stage procedure consisting of a low-temperature chitosan-Ag(+) complexation
      followed by a high-temperature reduction of the complex to form chitosan-capped
      silver nanoparticles (CS-capped Ag NPs). The surface plasmon resonance (SPR)
      absorption and fluorescence emission of the silver nanoparticles were influenced
      by the concentration and degradation time of chitosan, and the temperatures of
      the complexation and reduction reactions. The SPR absorption band was blue
      shifted while the intensities of emission and absorption were decreased after
      reacting the silver nanoparticles with Hg(2+) ions. The silver nanoparticles
      reacted with Hg(2+) were characterized by high resolution transmission electron
      microscopy (HRTEM), energy dispersive spectroscopy (EDS), X-ray photoelectron
      spectroscopy (XPS), and surface-enhanced Raman scattering spectroscopy (SERS).
      The results suggested that the particle growth and aggregation of the silver
      nanoparticles were caused by the adsorption of Hg(2+) and deposition of Hg(0) on
      the nanoparticle surface. Direct correlations of the SPR absorption and
      fluorescence emission with the concentration of Hg(2+) were useful for
      quantitative analysis of Hg(2+). It was possible to use the dual-functional
      silver nanoparticles as a colorimetric and fluorescent sensor for sensitive and
      selective detection of Hg(2+) ions. 

PMID- 25619931
TI  - Electron transfer in peptides.
AB  - In this review, we discuss the factors that influence electron transfer in
      peptides. We summarize experimental results from solution and surface studies and
      highlight the ongoing debate on the mechanistic aspects of this fundamental
      reaction. Here, we provide a balanced approach that remains unbiased and does not
      favor one mechanistic view over another. Support for a putative hopping mechanism
      in which an electron transfers in a stepwise manner is contrasted with
      experimental results that support electron tunneling or even some form of
      ballistic transfer or a pathway transfer for an electron between donor and
      acceptor sites. In some cases, experimental evidence suggests that a change in
      the electron transfer mechanism occurs as a result of donor-acceptor separation.
      However, this common understanding of the switch between tunneling and hopping as
      a function of chain length is not sufficient for explaining electron transfer in
      peptides. Apart from chain length, several other factors such as the extent of
      the secondary structure, backbone conformation, dipole orientation, the presence
      of special amino acids, hydrogen bonding, and the dynamic properties of a peptide
      also influence the rate and mode of electron transfer in peptides. Electron
      transfer plays a key role in physical, chemical and biological systems, so its
      control is a fundamental task in bioelectrochemical systems, the design of
      peptide based sensors and molecular junctions. Therefore, this topic is at the
      heart of a number of biological and technological processes and thus remains of
      vital interest. 

PMID- 25619930
TI  - Class III PI 3-kinase is the main source of PtdIns3P substrate and membrane
      recruitment signal for PIKfyve constitutive function in podocyte endomembrane
      homeostasis.
AB  - The evolutionarily conserved PIKfyve, which synthesizes PtdIns5P from PtdIns, and
      PtdIns(3,5)P2 from PtdIns3P, requires PtdIns3P as both an enzyme substrate and a
      membrane recruitment signal. Whereas the PtdIns3P source is undetermined, class
      III PI3K (Vps34), the only evolutionarily conserved of the eight mammalian PI3Ks,
      is presumed as a main candidate. A hallmark of PIKfyve deficiency is formation of
      multiple translucent cytoplasmic vacuoles seen by light microscopy in cells
      cultured in complete media. Such an aberrant phenotype is often observed in cells
      from conditional Vps34 knockout (KO) mice. To clarify the mechanism of Vps34 KO
      triggered vacuolation and the PtdIns3P source for PIKfyve functionality, here we
      have characterized a podocyte cell type derived from Vps34fl/fl mice, which, upon
      Cre-mediated gene KO, robustly formed cytoplasmic vacuoles resembling those in
      PikfyveKO MEFs. Vps34wt, expressed in Vps34KO podocytes restored the normal
      morphology, but only if the endogenous PIKfyve activity was intact. Conversely,
      expressed PIKfyvewt rescued completely the vacuolation only in PikfyveKO MEFs but
      not in Vps34KO podocytes. Analyses of phosphoinositide profiles by HPLC and
      localization patterns by a PtdIns3P biosensor revealed that Vps34 is the main
      supplier of localized PtdIns3P not only for PIKfyve activity but also for
      membrane recruitment. Concordantly, Vps34KO podocytes had severely reduced steady
      state levels of both PtdIns(3,5)P2 and PtdIns5P, along with PtdIns3P. We further
      revealed a plausible physiologically-relevant Vps34-independent PtdIns3P supply
      for PIKfyve, operating through activated class I PI3Ks. Our data provide the
      first evidence that the vacuolation phenotype in Vps34KO podocytes is due to
      PIKfyve dysfunction and that Vps34 is a main PtdIns3P source for constitutive
      PIKfyve functionality.

PMID- 25619932
TI  - Small molecule inhibitors of Clostridium difficile toxin B-induced cellular
      damage.
AB  - Clostridium difficile causes life-threatening diarrhea through the actions of its
      homologous toxins TcdA and TcdB on human colonocytes. Therapeutic agents that
      block toxin-induced damage are urgently needed to prevent the harmful
      consequences of toxin action that are not addressed with current antibiotic-based
      treatments. Here, we developed an imaging-based phenotypic screen to identify
      small molecules that protected human cells from TcdB-induced cell rounding. A
      series of structurally diverse compounds with antitoxin activity were identified
      and found to act through one of a small subset of mechanisms, including direct
      binding and sequestration of TcdB, inhibition of endosomal maturation, and
      noncompetitive inhibition of the toxin glucosyltransferase activity. Distinct
      classes of inhibitors were used further to dissect the determinants of the toxin
      mediated necrosis phenotype occurring at higher doses of toxin. These findings
      validate and inform novel targeting strategies for discovering small molecule
      agents to treat C. difficile infection. 

PMID- 25619933
TI  - Combined mitigation of the gastrointestinal and hematopoietic acute radiation
      syndromes by an LPA2 receptor-specific nonlipid agonist.
AB  - Pharmacological mitigation of injuries caused by high-dose ionizing radiation is
      an unsolved medical problem. A specific nonlipid agonist of the type 2 G protein
      coupled receptor for lysophosphatidic acid (LPA2) 2-[4-(1,3-dioxo-1H,3H
      benzoisoquinolin-2-yl)butylsulfamoyl]benzoic acid (DBIBB) when administered with
      a postirradiation delay of up to 72 hr reduced mortality of C57BL/6 mice but not
      LPA2 knockout mice. DBIBB mitigated the gastrointestinal radiation syndrome,
      increased intestinal crypt survival and enterocyte proliferation, and reduced
      apoptosis. DBIBB enhanced DNA repair by augmenting the resolution of gamma-H2AX
      foci, increased clonogenic survival of irradiated IEC-6 cells, attenuated the
      radiation-induced death of human CD34(+) hematopoietic progenitors and enhanced
      the survival of the granulocyte/macrophage lineage. DBIBB also increased the
      survival of mice suffering from the hematopoietic acute radiation syndrome after
      total-body irradiation. DBIBB represents a drug candidate capable of mitigating
      acute radiation syndrome caused by high-dose gamma-radiation to the hematopoietic
      and gastrointestinal system. 

PMID- 25619935
TI  - Generating site-specifically modified proteins via a versatile and stable
      nucleophilic carbon ligation.
AB  - There is a need for facile chemistries that allow for chemo- and regioselectivity
      in bioconjugation reactions. To address this need, we are pioneering site
      specific bioconjugation methods that use formylglycine as a bioorthogonal handle
      on a protein surface. Here we introduce aldehyde-specific bioconjugation
      chemistry, the trapped-Knoevenagel ligation. The speed and stability of the
      trapped-Knoevenagel ligation further advances the repertoire of aldehyde-based
      bioconjugations and expands the toolbox for site-specific protein modifications.
      The trapped-Knoevenagel ligation reaction can be run at near neutral pH in the
      absence of catalysts to produce conjugates that are stable under physiological
      conditions. Using this new ligation, we generated an antibody-drug conjugate that
      demonstrates excellent efficacy in vitro and in vivo. 

PMID- 25619934
TI  - Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for
      treatment of chronic viral infection.
AB  - Inhibition of host-encoded targets, such as the cyclophilins, provides an
      opportunity to generate potent high barrier to resistance antivirals for the
      treatment of a broad range of viral diseases. However, many host-targeted agents
      are natural products, which can be difficult to optimize using synthetic
      chemistry alone. We describe the orthogonal combination of bioengineering and
      semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a
      known cyclophilin inhibitor of mixed nonribosomal peptide/polyketide origin, to
      generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor
      of hepatitis B virus, hepatitis C virus (HCV), and HIV-1 replication, shows
      minimal inhibition of major drug transporters, and has a high barrier to
      generation of both HCV and HIV-1 resistance. 

PMID- 25619936
TI  - CRISPR-Cas9-based photoactivatable transcription system.
AB  - Targeted endogenous gene activation is necessary for understanding complex gene
      networks and has great potential in medical and industrial applications. The
      CRISPR-Cas system offers simple and powerful tools for this purpose. However,
      these CRISPR-Cas-based tools for activating user-defined genes are unable to
      offer precise temporal control of gene expression, despite the fact that many
      biological phenomena are regulated by highly dynamic patterns of gene expression.
      Here we created a light-inducible, user-defined, endogenous gene activation
      system based on CRISPR-Cas9. We demonstrated that this CRISPR-Cas9-based
      transcription system can allow rapid and reversible targeted gene activation by
      light. In addition, using this system, we have exemplified photoactivation of
      multiple user-defined endogenous genes in mammalian cells. The present CRISPR
      Cas9-based transcription system offers simple and versatile approaches for
      precise endogenous gene activation in basic biological research and biotechnology
      applications. 

PMID- 25619937
TI  - Role of topological charge stabilization in protomeric tautomerism.
AB  - Protomeric tautomerism is analyzed in view of the topological charge
      stabilization rules. Based on Huckel molecular orbital considerations and modern
      DFT calculations, it was found that the branching of amino or hydroxyl groups
      significantly contributes to the stability of major species through the first-
      and second-order perturbations with respect to the isoelectronic hydrocarbon.
      While amino-imino tautomerism is almost completely dominated by topological
      charge stabilization, hydroxyl-oxo tautomerism is affected by changes in the
      resonance integral of C-O/C?O bonds. Nevertheless, apart from side effects such
      as hydrogen bonds or solvent effects, a quantitative preference rule for the
      prediction of the tautomeric stability can be developed using topological pi
      electron energetics. As well as the analyses of simple bases, applications to
      complex or extended systems are exemplified analyzing purine bases, polyguanide,
      and polyuret. The present approach can be useful in conjunction with chemical
      intuition that comes from conventional valence bond theory. 

PMID- 25619938
TI  - Preparation of 17beta-estradiol-imprinted material by surface-initiated atom
      transfer radical polymerization and its application.
AB  - A novel 17beta-estradiol molecularly imprinted polymer was grafted onto the
      surface of initiator-immobilized silica by surface-initiated atom transfer
      radical polymerization. The resulting molecularly imprinted polymer was
      characterized by elemental analysis and thermogravimetric analysis. The binding
      property of molecularly imprinted polymer for 17beta-estradiol was also studied
      with both static and dynamic methods. The results showed that the molecularly
      imprinted polymer possessed excellent recognition capacity for 17beta-estradiol
      (180.65 mg/g at 298 K), and also exhibited outstanding selectivity for 17beta
      estradiol over the other competitive compounds (such as testosterone and
      progesterone). Then, the determination of trace 17beta-estradiol in beef samples
      was successfully developed by using molecularly imprinted polymer solid-phase
      extraction coupled with high-performance liquid chromatography. The limit of
      detection was 0.25 ng/mL, and the amount of 17beta-estradiol in beef samples was
      detected at 2.83 ng/g. This work proposed a sensitive, rapid, reliable, and
      convenient approach for the determination of trace 17beta-estradiol in
      complicated beef samples. 

PMID- 25619939
TI  - Identification of suitable genes contributes to lung adenocarcinoma clustering by
      multiple meta-analysis methods.
AB  - BACKGROUND: With the widespread application of high-throughput technology,
      numerous meta-analysis methods have been proposed for differential expression
      profiling across multiple studies. OBJECTIVES: We identified the suitable
      differentially expressed (DE) genes that contributed to lung adenocarcinoma (ADC)
      clustering based on seven popular multiple meta-analysis methods. METHODS: Seven
      microarray expression profiles of ADC and normal controls were extracted from the
      ArrayExpress database. The Bioconductor was used to perform the data preliminary
      preprocessing. Then, DE genes across multiple studies were identified.
      Hierarchical clustering was applied to compare the classification performance for
      microarray data samples. The classification efficiency was compared based on
      accuracy, sensitivity and specificity. RESULTS: Across seven datasets, 573 ADC
      cases and 222 normal controls were collected. After filtering out unexpressed and
      noninformative genes, 3688 genes were remained for further analysis. The
      classification efficiency analysis showed that DE genes identified by sum of
      ranks method separated ADC from normal controls with the best accuracy,
      sensitivity and specificity of 0.953, 0.969 and 0.932, respectively. The gene set
      with the highest classification accuracy mainly participated in the regulation of
      response to external stimulus (P = 7.97E-04), cyclic nucleotide-mediated
      signaling (P = 0.01), regulation of cell morphogenesis (P = 0.01) and regulation
      of cell proliferation (P = 0.01). CONCLUSIONS: Evaluation of DE genes identified
      by different meta-analysis methods in classification efficiency provided a new
      perspective to the choice of the suitable method in a given application. Varying
      meta-analysis methods always present varying abilities, so synthetic
      consideration should be taken when providing meta-analysis methods for particular
      research.

PMID- 25619940
TI  - Schwannoma of the Tongue.

PMID- 25619941
TI  - Defects in silicene: vacancy clusters, extended line defects, and Di-adatoms.
AB  - Defects are almost inevitable during the fabrication process, and their existence
      strongly affects thermodynamic and (opto)electronic properties of two-dimensional
      materials. Very recent experiments have provided clear evidence for the presence
      of larger multi-vacancies in silicene, but their structure, stability, and
      formation mechanism remain largely unexplored. Here, we present a detailed
      theoretical study of silicene monolayer containing three types of defects:
      vacancy clusters, extended line defects (ELDs), and di-adatoms. First-principles
      calculations, along with ab initio molecular dynamics simulations, revealed the
      coalescence tendency of small defects and formation of highly stable vacancy
      clusters. The 5|8|5 ELD - the most favorable extended defect in both graphene and
      silicene sheets - is found to be easier to form in the latter case due to the
      mixed sp(2)/sp(3) hybridization of silicon. In addition, hybrid functional
      calculations that contain part of the Hatree-Fock exchange energy demonstrated
      that the introduction of single and double silicon adatoms significantly enhances
      the stability of the system, and provides an effective approach on tuning the
      magnetic moment and band gap of silicene. 

PMID- 25619942
TI  - Specioside ameliorates oxidative stress and promotes longevity in Caenorhabditis
      elegans.
AB  - Specioside (6-O-coumaroylcatalpol) is an iridoid glucoside which possesses
      multifunctional activities viz. analgesic, antidyspeptic, astringent, liver
      stimulating and wound healing properties. The present study for the first time
      delineates stress alleviating and lifespan prolonging action of specioside (SPC),
      isolated from Stereospermum suaveolens in the free living, multicellular nematode
      model Caenorhabditis elegans. A strong correlation between lifespan extension and
      stress modulation in adult worms was established in a dose dependent manner. The
      dietary intake of this phytomolecule elevated juglone induced oxidative and heat
      induced thermal stress tolerance in C. elegans. On evaluation, it was found that
      25 MUM dose of SPC significantly extended lifespan by 15.47% (P<=0.0001) with
      reduction in stress level. Furthermore, SPC enhanced mean survival in mev-1
      mutant suggesting its oxidative stress reducing potential. Furthermore, SPC
      augmented stress modulatory enzymes superoxide dismutase (SOD) and catalase (CAT)
      level in C. elegans. Altogether, these findings broaden current perspectives
      concerning stress alleviating potentials of SPC and have implications in
      development of therapeutics for curing age related disorders.

PMID- 25619943
TI  - Thermal stability, antioxidant, and anti-inflammatory activity of curcumin and
      its degradation product 4-vinyl guaiacol.
AB  - Curcumin is a secondary plant metabolite present in Curcuma longa L. Since
      curcumin is widely used as a food colorant in thermally processed food it may
      undergo substantial chemical changes which in turn could affect its biological
      activity. In the current study, curcumin was roasted at 180  degrees C up to 70
      minutes and its kinetic of degradation was analyzed by means of HPLC-PDA and LC
      MS, respectively. Roasting of curcumin resulted in the formation of the
      degradation products vanillin, ferulic acid, and 4-vinyl guaiacol. In cultured
      hepatocytes roasted curcumin as well as 4-vinyl guaiacol enhanced the
      transactivation of the redox-regulated transcription factor Nrf2, known to be
      centrally involved in cellular stress response and antioxidant defense
      mechanisms. The antioxidant enzyme paraoxonase 1 was induced by roasted curcumin
      and 4-vinyl guaiacol. Furthermore, roasted curcumin and 4-vinyl guaiacol
      decreased interleukin-6 gene expression in lipopolysaccharide stimulated murine
      macrophages. Current data suggest that curcumin undergoes degradation due to
      roasting and its degradation product exhibit significant biological activity in
      cultured cells. 

PMID- 25619944
TI  - Cross-sectional study of brucellosis in Jordan: Prevalence, risk factors and
      spatial distribution in small ruminants and cattle.
AB  - Brucellosis is considered endemic in many Middle Eastern countries including
      Jordan. To determine the frequency, risk factors and spatial distribution of
      ruminant brucellosis in Jordan, a nationwide cross-sectional study was conducted.
      Small ruminant flocks (n=333) and cattle herds (n=204) were randomly selected,
      and their disease status was ascertained by testing individual serum samples
      using the Rose Bengal Test and a competitive ELISA (sheep and goats) and milk
      samples using an indirect ELISA (cattle). Information on putative risk factors
      was collected using standardized questionnaires. A logistic model with a binomial
      outcome was built to identify risk factors for being seropositive. The estimated
      true seroprevalence values were 18.1% (95% CI: 11-25.3) (cattle-only herds),
      22.2% (95% CI: 16.5-28.8) (sheep flocks), 45.4% (95% CI: 30.3-61.6) (goat herds),
      70.4% (95% CI: 55.5-84.9) (mixed sheep-goat flocks), 34.3% (95% CI: 28.4, 40.4)
      (all small ruminant flocks) and 38.5% (95% CI: 24.3-51.8) (mixed herds of cattle
      and small ruminants). Only 1.5% of small ruminant flocks were vaccinated. The
      seroprevalence was higher in northern areas, where livestock density is also
      higher. The logistic model fitted the data well and had a very high predictive
      ability. In the small ruminant model, five variables were significantly
      associated with a higher odds of seropositivity: lending/borrowing rams (OR=8.9,
      95% CI: 3.0-26.1), feeding aborted material to dogs (OR=8.0, 95% CI: 3.5-18.1)
      the presence of goats (OR=6.9, 95% CI: 3.1-15.4), introducing new animals to the
      flock (OR=5.8, 95% CI: 2.5-13.6), and a large flock size (OR=2.2, 95% CI: 1.0
      4.6). Conversely, separating newly introduced animals (OR=0.16, 95% CI: 0.05
      0.47), separating animals that had aborted (OR=0.19, 95% CI: 0.08-0.46) and using
      disinfectants to clean pens (OR=0.37, 95% CI: 0.16-0.83) were significantly
      associated with a lower odds of being seropositive. The main risk factor for
      cattle herds being seropositive was the introduction of new animals (OR=11.7, 95%
      CI: 2.8-49.4); while separation of newly introduced animals (OR=0.09, 95% CI:
      0.03-0.29), herd disinfection (OR=0.04, 95% CI: 0.01-0.15) and having calving
      pens (OR=0.14, 95% CI: 0.05-0.43) significantly reduced the odds of infection.
      Brucellosis is endemic at high levels across Jordan, and the current vaccination
      programme, which is limited to small ruminants, has very low coverage. A revised
      brucellosis control programme is required in Jordan. Given the high baseline
      prevalence, it should be based on vaccination accompanied by measures to promote
      hygiene and husbandry practices that minimize the risk of introduction and
      maintenance of Brucella spp., and thereby the risk of human infection. 

PMID- 25619945
TI  - A silk-based encapsulation platform for pancreatic islet transplantation improves
      islet function in vivo.
AB  - The success of pancreatic islet (PI) transplantation is challenged by PI
      functional damage during the peritransplantation period. A silk-based
      encapsulation platform including mesenchymal stromal cells (MSCs) was evaluated
      for islet cell delivery in vivo. Islet equivalents (IEQs) were transplanted into
      the epididymal fat pads of mice with streptozotocin-induced diabetes. Three PI
      combinations were tested: (A) co-encapsulated in silk with MSCs; (b) encapsulated
      in silk alone; or (c) pelleted. Blood glucose levels were monitored and
      intraperitoneal glucose tolerance test (IPGTT) was performed upon return to
      euglycaemia. Grafts were removed for histology and cytokine content analysis.
      Mice with PI grafts in silk showed a prompt return to euglycaemia. IPGTT was
      significantly improved with PI in silk with MSCs, compared to PI in silk alone or
      pelleted. Both Th1 and Th2 cytokines were increased in PI grafts in silk, but Th1
      cytokines were decreased significantly with PI and MSC co-encapsulation.
      Histological analysis showed osteogenesis and chondrogenesis in the silk grafts
      containing MSCs. Future studies will evaluate MSC stability and function in vivo
      and improve silk biocompatibility for applications in islet transplantation.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25619946
TI  - Mobilization of endothelial progenitor cells in acute cardiovascular events in
      the PROCELL study: time-course after acute myocardial infarction and stroke.
AB  - The mobilization pattern and functionality of endothelial progenitor cells after
      an acute ischemic event remain largely unknown. The aim of our study was to
      characterize and compare the short- and long-term mobilization of endothelial
      progenitor cells and circulating endothelial cells after acute myocardial
      infarction or atherothrombotic stroke, and to determine the relationship between
      these cell counts and plasma concentrations of vascular cell adhesion molecule
      (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial
      damage and inflammation. In addition, we assessed whether endothelial progenitor
      cells behave like functional endothelial cells. We included 150 patients with
      acute myocardial infarction or atherothrombotic stroke and 145 controls.
      Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating
      endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in
      controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and
      180 days after the event. Myocardial infarction patients had higher counts of
      endothelial progenitor cells and circulating endothelial cells than the controls
      (201.0/mL vs. 57.0/mL; p<0.01 and 181.0/mL vs. 62.0/mL; p<0.01). Endothelial
      progenitor cells peaked at 30 days post-infarction (201.0/mL vs. 369.5/mL;
      p<0.01), as did VCAM-1 (573.7 ng/mL vs. 701.8 ng/mL; p<0.01). At 180 days post
      infarction, circulating endothelial cells and VWF decreased, compared to
      baseline. In stroke patients, the number of endothelial progenitor cells - but
      not circulating endothelial cells - was higher than in controls (90.0/mL vs.
      37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however,
      VCAM-1 peaked (628.1/mL vs. 869.1/mL; p<0.01) but there was no significant change
      in endothelial progenitor cells (90/mL vs. 78/mL; p<0.34). At 180 days after
      stroke, circulating endothelial cells and VWF decreased, compared to baseline.
      Cultured endothelial progenitor cells from controls and myocardial infarction
      patients had endothelial phenotype characteristics and exhibited functional
      differences in adhesion and Ca(2+) influx, but not in proliferation and
      vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization
      of endothelial progenitor cells peaked at 30 days after the ischemic event.
      Although a similar VCAM-1 kinetic was observed in stroke patients, endothelial
      progenitor cells did not increase. Endothelial progenitor cells had mature
      endothelial capabilities in vitro.

PMID- 25619947
TI  - Alveolar rhabdomyosarcoma masquerading as Burkitt's lymphoma in bone marrow.

PMID- 25619948
TI  - Transcriptomic analysis reveals the roles of microtubule-related genes and
      transcription factors in fruit length regulation in cucumber (Cucumis sativus
      L.).
AB  - Cucumber (Cucumis sativus L.) fruit is a type of fleshy fruit that is harvested
      immaturely. Early fruit development directly determines the final fruit length
      and diameter, and consequently the fruit yield and quality. Different cucumber
      varieties display huge variations of fruit length, but how fruit length is
      determined at the molecular level remains poorly understood. To understand the
      genes and gene networks that regulate fruit length in cucumber, high throughout
      RNA-Seq data were used to compare the transcriptomes of early fruit from two near
      isogenic lines with different fruit lengths. 3955 genes were found to be
      differentially expressed, among which 2368 genes were significantly up-regulated
      and 1587 down-regulated in the line with long fruit. Microtubule and cell cycle
      related genes were dramatically activated in the long fruit, and transcription
      factors were implicated in the fruit length regulation in cucumber. Thus, our
      results built a foundation for dissecting the molecular mechanism of fruit length
      control in cucumber, a key agricultural trait of significant economic importance.

PMID- 25619949
TI  - Social cues are unlikely to be the single cause for early reproduction in urban
      European blackbirds (Turdus merula).
AB  - Despite urban ecology being an established field of research, there is still
      surprisingly little information about the relative contribution of specific
      environmental factors driving the observed changes in the behavior and physiology
      of city dwellers. One of the most reported effects of urbanization is the
      advanced phenology observed in birds. Many factors have been suggested to
      underline such effect, including warmer microclimate, anthropogenic food supply
      and light pollution. Since social stimuli are known to affect reproductive timing
      and breeding density is usually higher in urban populations compared to rural
      ones, we experimentally tested whether social interactions could advance the
      onset of reproduction in European blackbirds (Turdus merula). We housed male
      blackbirds of rural and urban origins with or without a conspecific female, and
      recorded their seasonal variation in gonadal size and production of luteinizing
      hormone (LH). Paired and unpaired males of both urban and rural origins did not
      significantly differ in their timing of gonadal growth. Moreover, rural and urban
      birds did not differ in their response to the social stimuli, rather they became
      reproductively active at the same time, a result that confirms previous studies
      that attributed the difference in reproductive timing observed in the field to
      phenotypic plasticity. We conclude that social stimuli do not contribute
      substantially to the observed early onset of reproductive physiology in urban
      bird species, rather other factors such as light pollution are likely to be
      stronger drivers of these physiological changes.

PMID- 25619950
TI  - Olfactory and gustatory functions and its relation to body weight.
AB  - In the present study we investigated the influence of body weight as defined by
      BMI on gustatory and olfactory perception. A total of 66 healthy adults (41
      females; 25 males) participated in psychophysical measurements using the
      "Sniffin' Sticks" test and "Taste Strips" test. Odor thresholds as well as
      discrimination and identification performance were determined. Tests of gustatory
      function involved the identification and thresholds of sweet, sour, salty, or
      bitter taste. In this study, all subjects were healthy participants in a middle
      age range (between 20 and 56 years of age). Persons with an extreme BMI value
      were excluded. Subjects were classified according to their BMI in four groups:
      (1) 15-19.9 kg/m, (2) 20-24.9 kg/m, (3) 25-29.9 kg/m, and (4) >30 kg/m. We did
      not observe an overall effect of BMI on general sensory sensitivity. There was a
      significant influence of BMI on olfactory thresholds (F(3,62)=2.79; p<0.047)
      which increased with increasing BMI. In a similar line, the gustatory thresholds
      for "salty" were significantly higher with higher BMI (F(3,62)=3.06; p<0.035).
      Olfactory discrimination and identification was not affected by BMI. Thresholds
      for odor and sweet or salty taste were also correlated. Our data show that body
      weight influences gustatory and olfactory perception in healthy adults.
      Increasing BMI is associated with a decrease in olfactory and taste sensitivity.
      These findings may have implications for the understanding of pathophysiological
      mechanisms in patients.

PMID- 25619951
TI  - Severe maternal undernutrition and post-weaning behavior of rabbits.
AB  - The objective of the present experiment was to investigate the implications of
      severe maternal undernutrition on the post-weaning behavior of rabbits. Thirty
      two does were randomly assigned to four groups: the control group (C) that was
      fed 100% of the recommended energy maintenance requirements throughout pregnancy
      and lactation and the U1, U2 and U3 groups that were fed 50% of the recommended
      energy maintenance requirements between the 6th and the 19th day of pregnancy,
      between the 20th and the 27th day of pregnancy and between the 3rd and the 10th
      day of lactation, respectively. At the age of 50 and 65 days, behavior of rabbits
      in cages was recorded and rabbits were further subjected to an open-field test; a
      paradigm used as an indicator of fear and emotional distress. Significant
      differences were found between the U2 and the other experimental groups for the
      duration of eating and drinking, and duration of locomotory and investigatory
      behaviors (P<0.05). At the age of 65 days, duration of comfort behaviors was also
      lower in the U2 compared to the other groups (P<0.05). On the other hand,
      duration of resting appeared to be the highest in the group of rabbits born from
      undernourished does between the 20th and the 27th day of pregnancy (P<0.05).
      Duration of resting was significantly increased, although frequency and duration
      of eating and drinking were significantly decreased at the age of 65 days
      (P<0.05). Male rabbits had greater values for locomotory and investigatory
      behaviors, and duration of eating and drinking compared to the females (P<0.01).
      A decreased activity of rabbits during the light period was observed (as
      expected), whereas an increase in duration of locomotory and investigatory
      behaviors was observed during the first four and the last 4h of the light and
      dark periods, respectively (P<0.05). Rabbits born from the U1 and U2 group of
      does displayed increased rates of latency to leave the start position compared to
      the other groups during the implementation of the open-field test (P<0.05). No
      other significant differences in the exhibition of the examined behaviors were
      found between the treatment groups, with the exception of 'moving forelegs'
      activity that had the lowest value in the U3 group of rabbits. It is concluded
      that severe maternal undernutrition (50% of the recommended maintenance
      requirements) especially between the 20th and the 27th day of pregnancy has
      significant effects on the exhibition of rabbits' post-weaning behavior, since
      the offspring from the U2 undernourished does were significantly less active
      compared to the other experimental groups.

PMID- 25619952
TI  - The novelty-seeking phenotype modulates the long-lasting effects of adolescent
      MDMA exposure.
AB  - Exposure to drugs such as ethanol or cocaine during adolescence induces
      alterations in the central nervous system that are modulated by the novelty
      seeking trait. Our aim was to evaluate the influence of this trait on the long
      term effects of MDMA administration during adolescence on spontaneous behavior
      and conditioned rewarding effects in adulthood. Adolescent mice were classified
      as high or low novelty seekers (HNS or LNS) according to the hole-board test and
      received either MDMA (0, 10 or 20mg/kg PND 33-42) or saline. Three weeks later,
      having entered adulthood (PND>68), one set of mice performed the elevated plus
      maze and social interaction tests, while another set performed the conditioning
      place preference (CPP) test induced by cocaine-(1mg/kg) or MDMA-(1mg/kg). Only
      HNS mice treated with MDMA during adolescence acquired CPP in adulthood with a
      non-effective dose of cocaine or MDMA. Although it did not produce changes in
      motor activity, exposure to MDMA during adolescence was associated with more
      aggressive behaviors (threat and attack) and increased social contacts in HNS
      mice, while an anxiolytic effect was noted in LNS mice pre-treated with the
      highest dose of MDMA (20mg/kg). Administration of MDMA (10 or 20mg/kg) induced a
      decrease in DA levels in the striatum in LNS mice only and lower striatal
      serotonin levels in mice treated with the highest MDMA dose. Our findings show
      that adolescent MDMA exposure results in higher sensitivity to the conditioned
      reinforcing properties of MDMA and cocaine in adult HNS mice, which suggests that
      the relationship between exposure to MDMA in adolescence and a higher probability
      of substance is a feature of high novelty seekers only. 

PMID- 25619953
TI  - Effect of low-level laser therapy on dental root cementum remodeling in rats.
AB  - OBJECTIVE: To investigate the amount of the cementum layer formed over the rat's
      dental root surfaces by daily application of low-level laser therapy (LLLT) for 2
      weeks. METHODS: Twelve female Sprague-Dawley (SD) rats were divided into two
      groups: six rats received daily LLLT (Ga-Al-As, 830 nm), and six rats received no
      treatment (control). The treatment lasted 2 weeks. In vivo Micro-CT imaging
      analyzed the root's hard tissue volumetric changes. The cementum thickness was
      evaluated histologically. RESULTS: Total cementum thicknesses in the LLLT group
      increased significantly (p = 0.015) compared to the control group. This
      significant increase in the cementum thickness, verified histologically, was not
      detectable during in vivo Micro-CT imaging, which showed no significant
      difference between the groups regarding the root hard tissues volumetric changes
      over the 2-week evaluation period. CONCLUSION: Two weeks of daily application of
      LLLT significantly increased rat's dental root cementum thickness as determined
      histologically. However, in vivo Micro-CT imaging failed to accurately reveal
      this cementum growth as it was not possible to differentiate dentinal changes.

PMID- 25619954
TI  - A novel water-soluble sulfonated porphyrin fluorescence sensor for sensitive
      assays of H2O2 and glucose.
AB  - Water soluble porphyrins have many perfect analytical figures of merit. A water
      soluble sulfonated porphyrin (H2TEHPPS) was used to build a novel platform for
      sensitive assays of hydrogen peroxide and glucose based on the different effects
      of Fe(2+) and Fe(3+) on H2TEHPPS. H2O2 or Fe(2+) alone cannot induce a
      fluorescence change in H2TEHPPS, but Fe(3+) can quench the fluorescence of
      H2TEHPPS significantly. Interestingly, glucose is oxidized to gluconolactone by
      GOD and generates an equivalent hydrogen peroxide, and the produced H2O2 also
      oxidizes Fe(2+) to Fe(3+) and causes the fluorescence quenching of H2TEHPPS.
      According to this, a sensitive sensor for hydrogen peroxide and glucose has been
      demonstrated, which can determine H2O2 and glucose in a relative simple and
      sensitive way. The detection limits were 1.3 * 10(-7) M and 3.2 * 10(-7) M for
      H2O2 and glucose, respectively. In addition, the glucose in serum samples was
      determined successfully using this sensing platform. It is also noteworthy that
      H2O2 can be released in almost all oxidations catalyzed by oxidases, which
      suggests that this newly proposed H2O2 probe can be readily extended to sense
      other oxidases and their specific substrates. 

PMID- 25619955
TI  - Candidate gene analysis of BRCA1/2 mutation-negative high-risk Russian breast
      cancer patients.
AB  - Twenty one DNA repair genes were analyzed in a group of 95 BC patients, who
      displayed clinical features of hereditary disease predisposition but turned out
      to be negative for mutations in BRCA1 and BRCA2 entire coding region as well as
      for founder disease-predisposing alleles in CHEK2, NBN/NBS1 and ATM genes. Full
      length sequencing of CHEK2 and NBN/NBS1 failed to identify non-founder mutations.
      The analysis of TP53 revealed a woman carrying the R282W allele; further testing
      of additional 108 BC patients characterized by a very young age at onset (35
      years or earlier) detected one more carrier of the TP53 germ-line defect. In
      addition, this study confirmed non-random occurrence of PALB2 truncating
      mutations in Russian hereditary BC patients. None of the studied cases carried
      germ-line defects in recently discovered hereditary BC genes, BRIP1, FANCC,
      MRE11A and RAD51C. The analysis of genes with yet unproven BC-predisposing
      significance (BARD1, BRD7, CHEK1, DDB2, ERCC1, EXO1, FANCG, PARP1, PARP2, RAD51,
      RNF8, WRN) identified single women carrying a protein-truncating allele, WRN
      R1406X. DNA sequencing of another set of 95 hereditary BC cases failed to reveal
      additional WRN heterozygous genotypes. Since WRN is functionally similar to the
      known BC-predisposing gene, BLM, it deserves to be analyzed in future hereditary
      BC studies. Furthermore, this investigation revealed a number of rare missense
      germ-line variants, which are classified as probably protein-damaging by online
      in silico tools and therefore may require further consideration. 

PMID- 25619956
TI  - Investigations into distribution of lidocaine in human autopsy material.
AB  - With screening methods in the legal medicine drugs were often detected in autopsy
      material. In this study the antiarrhythmic and the local anesthetic drug
      lidocaine could be proved in fifty-one cases and determined in different autopsy
      materials. For the first time the comparison of so many distribution patterns of
      lidocaine in human compartments was possible. A liquid-liquid extraction
      procedure, a standard addition method and LC/MS/MS were used for analytics. The
      measured concentrations in blood were in the therapeutic range or lower. The time
      between lidocaine application and death was given in twenty-nine cases. These
      data were very helpful to estimate and interpret the distribution process of
      lidocaine between application and death. This time exerted a crucial influence on
      the distribution of lidocaine in the compartments. Most of the intravenous
      applicated lidocaine was found in heart blood after a very short time of
      distribution. Afterwards the highest concentrations were measured in brain. Later
      the highest concentration was found in the kidney samples or in urine. If the
      time between lidocaine application and death is known, the results of this study
      can be used to deepen the knowledge of its pharmacokinetics. If this time is
      unknown, the circumstances and the causes of death can be better explained.

PMID- 25619957
TI  - Diversity and prevalence of gastrointestinal parasites in seven non-human
      primates of the Tai National Park, Cote d'Ivoire.
AB  - Parasites and infectious diseases are well-known threats to primate populations.
      The main objective of this study was to provide baseline data on fecal parasites
      in the cercopithecid monkeys inhabiting Cote d'Ivoire's Tai National Park. Seven
      of eight cercopithecid species present in the park were sampled: Cercopithecus
      diana, Cercopithecus campbelli, Cercopithecus petaurista, Procolobus badius,
      Procolobus verus, Colobus polykomos, and Cercocebus atys. We collected 3142
      monkey stool samples between November 2009 and December 2010. Stool samples were
      processed by direct wet mount examination, formalin-ethyl acetate concentration,
      and MIF (merthiolate, iodine, formalin) concentration methods. Slides were
      examined under microscope and parasite identification was based on the morphology
      of cysts, eggs, and adult worms. A total of 23 species of parasites was recovered
      including 9 protozoa (Entamoeba coli, Entamoeba histolytica/dispar, Entamoeba
      hartmanni, Endolimax nana, Iodamoeba butschlii, Chilomastix mesnili, Giardia sp.,
      Balantidium coli, and Blastocystis sp.), 13 nematodes (Oesophagostomum sp.,
      Ancylostoma sp., Anatrichosoma sp., Capillariidae Gen. sp. 1, Capillariidae Gen.
      sp. 2, Chitwoodspirura sp., Subulura sp., spirurids [cf Protospirura muricola],
      Ternidens sp., Strongyloides sp., Trichostrongylus sp., and Trichuris sp.), and 1
      trematode (Dicrocoelium sp.). Diversity indices and parasite richness were high
      for all monkey taxa, but C. diana, C. petaurista, C. atys, and C. campbelli
      exhibited a greater diversity of parasite species and a more equitable
      distribution. The parasitological data reported are the first available for these
      cercopithecid species within Tai National Park. 

PMID- 25619958
TI  - CKD in disadvantaged populations.

PMID- 25619960
TI  - Correction: Programmable microfluidic synthesis of spectrally encoded
      microspheres.
AB  - Correction for 'Programmable microfluidic synthesis of spectrally encoded
      microspheres' by R. E. Gerver et al., Lab Chip, 2012, 12, 4716-4723. 

PMID- 25619962
TI  - Childhood onset of acquired neuromyotonia: association with a ganglioneuroma.

PMID- 25619959
TI  - Functional role of cellular senescence in biliary injury.
AB  - Cellular senescence is a state of irreversible cell cycle arrest that has been
      involved in many gastrointestinal diseases, including human cholestatic liver
      disorders. Senescence may play a role in biliary atresia, primary sclerosing
      cholangitis, cellular rejection, and primary biliary cirrhosis, four liver
      diseases affecting cholangiocytes and the biliary system. In this review, we
      examine proposed mechanisms of senescence-related biliary diseases, including
      hypotheses associated with the senescence-associated phenotype, induction of
      senescence in nearby cells, and the depletion of stem cell subpopulations.
      Current evidence for the molecular mechanisms of senescence in the previously
      mentioned diseases is discussed in detail, with attention to recent advances on
      the role of pathways associated with senescence-associated phenotype, stress
      induced senescence, telomere dysfunction, and autophagy. 

PMID- 25619963
TI  - Analysis of temporal and spatial trends of hydro-climatic variables in the Wei
      River Basin.
AB  - The Wei River is the largest tributary of the Yellow River in China. The
      relationship between runoff and precipitation in the Wei River Basin has been
      changed due to the changing climate and increasingly intensified human
      activities. In this paper, we determine abrupt changes in hydro-climatic
      variables and identify the main driving factors for the changes in the Wei River
      Basin. The nature of the changes is analysed based on data collected at twenty
      one weather stations and five hydrological stations in the period of 1960-2010.
      The sequential Mann-Kendall test analysis is used to capture temporal trends and
      abrupt changes in the five sub-catchments of the Wei River Basin. A non
      parametric trend test at the basin scale for annual data shows a decreasing trend
      of precipitation and runoff over the past fifty-one years. The temperature
      exhibits an increase trend in the entire period. The potential evaporation was
      calculated based on the Penman-Monteith equation, presenting an increasing trend
      of evaporation since 1990. The stations with a significant decreasing trend in
      annual runoff mainly are located in the west of the Wei River primarily
      interfered by human activities. Regression analysis indicates that human activity
      was possibly the main cause of the decline of runoff after 1970. 

PMID- 25619964
TI  - Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles
      established by multimodal imaging.
AB  - Atherosclerosis is a major cause of global morbidity and mortality that could
      benefit from novel targeted therapeutics. Recent studies have shown efficient and
      local drug delivery with nanoparticles, although the nanoparticle targeting
      mechanism for atherosclerosis has not yet been fully elucidated. Here we used in
      vivo and ex vivo multimodal imaging to examine permeability of the vessel wall
      and atherosclerotic plaque accumulation of fluorescently labeled liposomal
      nanoparticles in a rabbit model. We found a strong correlation between
      permeability as established by in vivo dynamic contrast enhanced magnetic
      resonance imaging and nanoparticle plaque accumulation with subsequent
      nanoparticle distribution throughout the vessel wall. These key observations will
      enable the development of nanotherapeutic strategies for atherosclerosis. 

PMID- 25619967
TI  - If I had a name like that... I would probably change it.

PMID- 25619965
TI  - Abnormal immunophenotype of the T-cell-receptor beta Chain in follicular-helper T
      cells of angioimmunoblastic T-cell lymphoma.
AB  - OBJECTIVE: Analysis for 24 variable regions of the T-cell-receptor beta chain by
      flow cytometry (Vbeta) is a new technique to detect clonal alpha-beta T
      lymphocytes and is characteristically performed on peripheral blood.
      Angioimmunoblastic T-cell lymphoma (AITL) has increased neoplastic follicular
      helper T cells (FHT), which often express CD10; but nonneoplastic, CD10-positive
      T cells may be associated with reactive lymphadenopathy and with B-cell
      lymphomas. This study documents the utility of Vbeta analysis of FHT in specimens
      of AITL from blood, from marrow, and from lymph nodes. METHODS: The electronic
      medical record in the flow cytometry laboratory was searched for specimens that
      were analyzed by flow cytometry for Vbeta and that were involved by AITL. Flow
      cytometry was performed for the following antigens: T-cell-associated proteins,
      CD10, CD56, CD94, CD161, killer-cell immunoglobulin-like receptors, alpha-beta T
      cell receptor, gamma-delta T-cell receptor, and Vbeta. RESULTS: Five patients had
      six specimens of blood (two), of bone marrow (one), or of lymph nodes (three).
      Immunophenotypic aberrances were detected for antigens: CD2 (2/6), CD3 (6/6), CD4
      (1/6), CD5 (1/6), CD7 (5/6), and CD45 (2/6). All abnormal T-cell populations
      expressed CD4, and most expressed CD10 (5/6). Four specimens were clonally
      restricted for Vbeta. Two specimens lacked the alpha-beta T-cell receptor and
      Vbeta. CONCLUSIONS: Vbeta analysis by flow cytometry can be used to detect clonal
      alpha-beta FHT in AITL, which may be difficult to diagnose with early
      involvement. Abnormal Vbeta expression on CD10-positive T cells confirms that FHT
      are the neoplastic cells.

PMID- 25619969
TI  - The use of CT scans in estimating age at death by examining the extent of
      ectocranial suture closure.
AB  - We examined the utility of CT scans in the evaluation of degree of ectocranial
      suture closure. Five cranial points (left and right midcoronal positions, left
      and right midlambdoidal positions, and the lambda) were evaluated in 231 CT scans
      using a three-point scoring system (open, partial closed, and closed). The slice
      increment and thickness varied between three groups of the scans. The results
      showed a good correlation between degree of suture closure and increasing age in
      each group. Young individuals (<40 years) and old individuals (>60 years) could
      be clearly distinguished from the middle-aged individuals. ANOVA test revealed no
      difference between two groups of scans and between left and right sides (p >
      0.05). Interobserver agreement was good, especially considering the score by
      sides. The results of this study create the base for developing a robust and
      simple method to estimate the age at death using CT scans. 

PMID- 25619970
TI  - Properties and functions of the storage sites of glycogen phosphorylase.
AB  - Glycogen phosphorylase (GP) is biologically active as a dimer of identical
      subunits. Each subunit has two distinct maltooligosaccharide binding sites: a
      storage site and a catalytic site. Our characterization of the properties of
      these sites suggested that GP activity consists of two activities: (i) binding to
      the glycogen molecule and (ii) phosphorolysis of the non-reducing-end glucose
      residues. Activity (i) is mainly due to the activities of the two storage sites,
      which depended on the ionic strength of the medium and were directly inhibited by
      cyclodextrins (CDs). Activity (i) is of benefit to GP because a high
      concentration of non-reducing-end glucose residues is localized on the surface of
      the glycogen molecule. Activity (ii), the total activity of the two catalytic
      sites, exhibited relatively little ionic strength dependence. Because the
      combined activity of (i) and (ii) is deduced using glycogen as an assay
      substrate, the sole activity of (ii) must be measured using small maltooligosyl
      substrates. By using a very low concentration of pyridylaminated maltohexaose, we
      demonstrated that the GP catalytic sites are active even in the presence of CDs,
      and that the actions of the catalytic site and the storage site are independent
      of each other. 

PMID- 25619971
TI  - A highly effective and adjustable dual plasmid system for O-GlcNAcylated
      recombinant protein production in E. coli.
AB  - O-GlcNAcylation is a ubiquitous, dynamic and reversible post-translational
      protein modification in metazoans, and it is catalysed and removed by O-GlcNAc
      transferase (OGT) and O-GlcNAcase, respectively. Prokaryotes lack endogenous OGT
      activity. It has been reported that coexpression of mammalian OGT with its target
      substrates in Escherichia coli produce O-GlcNAcylated recombinant proteins, but
      the plasmids used were not compatible, and the expression of both OGT and its
      target protein were induced by the same inducer. Here, we describe a compatible
      dual plasmid system for coexpression of OGT and its target substrate for O
      GlcNAcylated protein production in E. coli. The approach was validated using the
      CKII and p53 protein as control. This compatible dual plasmid system contains an
      arabinose-inducible OGT expression vector with a pUC origin and an isopropyl beta
      d-thiogalactopyranoside-inducible OGT target substrate expression vector bearing
      a p15A origin. The dual plasmid system produces recombinant proteins with varying
      O-GlcNAcylation levels by altering the inducer concentration. More importantly,
      the O-GlcNAcylation efficiency was much higher than the previously reported
      system. Altogether, we established an adjustable compatible dual plasmid system
      that can effectively yield O-GlcNAcylated proteins in E. coli. 

PMID- 25619972
TI  - What is your diagnosis? Synovial fluid from a dog.

PMID- 25619974
TI  - Immunological characterization of the gluten fractions and their hydrolysates
      from wheat, rye and barley.
AB  - Gluten proteins in wheat, rye and barley cause celiac disease, an autoimmune
      disorder of the small intestine, which affects approximately 1% of the world
      population. Gluten is comprised of prolamin and glutelin. Since avoidance of
      dietary gluten is the only option for celiac patients, a sensitive gluten
      detection and quantitation method is warranted. Most regulatory agencies have set
      a threshold of 20 ppm gluten in foods labeled gluten-free, based on the currently
      available ELISA methods. However, these methods may exhibit differences in gluten
      quantitation from different gluten-containing grains. In this study, prolamin and
      glutelin fractions were isolated from wheat, rye, barley, oats and corn. Intact
      and pepsin-trypsin (PT)-digested prolamin and glutelin fractions were used to
      assess their immunoreactivity and gluten recovery by three sandwich and two
      competitive ELISA kits. The Western blots revealed varied affinity of ELISA
      antibodies to gluten-containing grain proteins and no reactivity to oat and corn
      proteins. ELISA results showed considerable variation in gluten recoveries from
      both intact and PT-digested gluten fractions among different kits. Prolamin
      fractions showed higher gluten recovery compared to their respective glutelin
      fractions. Among prolamins, barley exhibited higher recovery compared to wheat
      and rye with most of the ELISA kits used. Hydrolysis resulted in reduced gluten
      recovery of most gluten fractions. These results suggest that the suitability of
      ELISA for accurate gluten quantitation is dependent upon various factors, such as
      grain source, antibody specificity, gluten proteins and the level of their
      hydrolysis in foods. 

PMID- 25619973
TI  - Succinobucol, a Lipid-Lowering Drug, Protects Against 3-Nitropropionic Acid
      Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Cells via
      Upregulation of Glutathione Levels and Glutamate Cysteine Ligase Activity.
AB  - Succinobucol (succinyl ester of probucol) is a lipid-lowering compound with anti
      inflammatory and antioxidant properties. Recent experimental evidence has
      highlighted the potential neuroprotective effects of succinobucol. In the present
      study, cultured neuroblastoma (SH-SY5Y) cells were used to investigate mechanisms
      mediating the potential protective effect of succinobucol against mitochondrial
      metabolic impairment and oxidative stress induced by 3-nitropropionic acid (3
      NP), a succinate dehydrogenase inhibitor that has been used in experimental
      models of the Huntington disease (HD). 3-NP decreased cellular viability after 24
      h of incubation. This decline in cellular viability was preceded by (i) reduced
      mitochondrial complex II activity, (ii) increased reactive species generation,
      (iii) decreased mitochondrial membrane potential (DeltaPsim), and (iv) diminished
      glutathione (GSH) levels. Succinobucol pretreatment (6 days) significantly
      prevented 3-NP-induced loss of cellular viability, generation of reactive oxygen
      species, and decrease of DeltaPsim. However, succinobucol pretreatment did not
      protect against 3-NP-induced inhibition of mitochondrial complex II activity,
      pointing to the mitigation of secondary events resultant from mitochondrial
      complex II inhibition. Succinobucol pretreatment (6 days) significantly increased
      (50 %) the levels of GSH in SH-SY5Y cells, and this event was paralleled by
      significant increases in glutamate cysteine ligase messenger RNA (mRNA)
      expression and activity (GCL; the first enzyme in the GSH biosynthesis). The
      present findings are the first to show that succinobucol increases GSH levels via
      upregulation of GCL activity (possibly through the activation of the nuclear
      (erythroid-derived 2)-related factor (Nrf2)/antioxidant response element (ARE)
      pathway), displaying protective effects against mitochondrial dysfunction-derived
      oxidative stress.

PMID- 25619975
TI  - Self-management support from the perspective of patients with a chronic
      condition: a thematic synthesis of qualitative studies.
AB  - BACKGROUND: Receiving adequate support seems to be crucial to the success of self
      management. Although different empirical studies separately examined patients'
      preferences for self-management support (SMS), an overview is lacking. OBJECTIVE:
      The aim of this qualitative review was to identify patients' needs with respect
      to SMS and to explore by whom this support is preferably provided. SEARCH
      STRATEGY: Qualitative studies were identified from Embase, MEDLINE OvidSP, Web of
      science, PubMed publisher, Cochrane central, the Cumulative Index to Nursing and
      Allied Health Literature (CINAHL) and PsycINFO. INCLUSION CRITERIA: Articles
      needed to meet all of the following criteria: (i) focuses on self-management,
      (ii) concerns adult patients with rheumatic diseases (rheumatoid arthritis and
      fibromyalgia), a variant of cancer or chronic kidney disease, (iii) explores
      support needs from the patients' perspective, (iv) uses qualitative methods and
      (v) published in English. DATA EXTRACTION AND SYNTHESIS: A thematic synthesis,
      developed by Thomas and Harden, was conducted of the 37 included studies. MAIN
      RESULTS: Chronic patients need instrumental support, psychosocial support and
      relational support from health-care professionals, family/friends and fellow
      patients to manage the chronic condition. Relational support is at the centre of
      the support needs and fuels all other types of support. DISCUSSION AND
      CONCLUSIONS: Patients do not self-manage on their own. Patients expect health
      care professionals to fulfil a comprehensive role. Support needs can be knitted
      together only when patients and professionals work together on the basis of
      collaborative partnership. Dynamics in support needs make it important to
      regularly assess patient needs.

PMID- 25619977
TI  - Moderate and extended neonatal resuscitations occur in one in 10 births and
      require specialist cover 24 hours a day.
AB  - AIM: Neonatal resuscitation requires minimal equipment, but the immediate
      availability of expert staff accounts for the largest proportion of the costs.
      Despite this, staff requirements and timetables are currently planned without
      comprehensive epidemiologic data. The aim of this study was to evaluate the
      staffing required for neonatal resuscitations in the delivery room. METHODS: We
      measured attendance for each specific role in a tertiary university-affiliated
      hospital and for four possible intervention levels: preparation time, basic
      paediatric care, moderate resuscitation and extended resuscitation. RESULTS:
      Between 2005 and 2012, resuscitation staff attended 11 561 of the 32 799 births:
      27.2% for preparation time, 17.7% for basic paediatric care, 6.4% for moderate
      resuscitation and 3.5% for extended resuscitation. Moderate and extended
      resuscitations occurred in roughly 10% of births and evenly during 24-h periods.
      Basic paediatric care levels were higher during weekday mornings, and extended
      resuscitations were uniformly distributed. However, there was a drop in all types
      of interventions around 7 a.m. to 8 a.m., when staff were changing shifts.
      CONCLUSION: Moderate and extended resuscitations occurred evenly over 24 h in
      roughly 10% of births, stressing the importance of having a highly competent
      neonatal team constantly available. All activities associated with resuscitation
      were lower during morning shift changes.

PMID- 25619978
TI  - Intracranial cystic meningiomas: A rare type of tumours.
AB  - INTRODUCTION: Intracranial cystic meningiomas are rare and preoperative diagnosis
      is difficult. The present study was performed to assess the clinical and
      radiological outcome of intracranial cystic meningiomas. METHODS: We performed a
      retrospective analysis of 13 patients (mean age: 49.9 years) who underwent
      surgical resection of intracranial cystic meningiomas from January 2006 to
      February 2014. There were 5 male and 8 female patients. The Glasgow Outcome Scale
      was used to assess the clinical outcome at 6 months. RESULTS: Headache was the
      main presenting clinical feature. Most of the tumours were located on the right
      side. The frontal convexity was the most common site. Gross total resection was
      performed in 10 patients. The most common histopathological type was
      meningothelial variety. CONCLUSION: Intracranial cystic meningiomas are usually
      benign that occur in relatively young patients. Resection of cysts that show
      contrast enhancement is essential to reduce recurrence.

PMID- 25619976
TI  - Handling and reporting of orchidectomy specimens with testicular cancer: areas of
      consensus and variation among 25 experts and 225 European pathologists.
AB  - AIMS: The handling and reporting of testicular tumours is difficult due to their
      rarity. METHODS AND RESULTS: A survey developed by the European Network of Uro
      Pathology (ENUP) and sent to its members and experts to assess the evaluation of
      testicular germ cell tumours. Twenty-five experts and 225 ENUP members replied.
      Areas of disagreement included immaturity in teratomas, reported by 32% of
      experts but 68% of ENUP. Although the presence of rete testis invasion was
      reported widely, the distinction between pagetoid and stromal invasion was made
      by 96% of experts but only 63% of ENUP. Immunohistochemistry was used in more
      than 50% of cases by 68% of ENUP and 12% of experts. Staging revealed the
      greatest areas of disagreement. Invasion of the tunica vaginalis without vascular
      invasion was interpreted as T1 by 52% of experts and 67% of ENUP, but T2 by the
      remainder. Tumour invading the hilar adipose tissue adjacent to the epididymis
      without vascular invasion was interpreted as T1: 40% of experts, 43% of ENUP; T2:
      36% of experts, 30% of ENUP; and T3: 24% of experts, 27% of ENUP. CONCLUSIONS:
      There is remarkable consensus in many areas of testicular pathology. Significant
      areas of disagreement included staging and reporting of histological types, both
      of which have the potential to impact on therapy.

PMID- 25619979
TI  - Deep brain stimulation of the subthalamic nucleus in Parkinson's disease 2003
      2013: Where are we another 10 years on?
AB  - High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is
      now ending its second decade as an established modality for treating Parkinson's
      disease (PD). Knowledge of the pathophysiology of PD and clinical applications
      for STN DBS is burgeoning. Despite this, the mechanism of how STN DBS works
      remains an enigma. Furthermore, motor symptoms have been seen as a focus for
      improved quality of life after STN DBS yet non-motor symptoms also play an
      integral role in determining treatment outcome. In this paper, new evidence for
      the mechanisms of action of STN DBS is discussed and the impact of the therapy on
      motor and non-motor symptoms of PD is analysed. Future directions of treatment
      and emerging technologies are also reviewed. 

PMID- 25619981
TI  - Liquid chromatography coupled with tandem mass spectrometry to characterise trace
      levels of cyanobacteria and dinoflagellate toxins in suspended solids and
      sediments.
AB  - Microcystins, anatoxins and okadaic acid are toxins produced by freshwater
      cyanobacteria and marine dinoflagellates. These toxins have been the responsible
      for the illness and death of biota and humans. To determine their presence in
      water during blooms, sensitive analytical methods are needed. In this study, we
      have developed a new liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method for fast multiresidue determination of five toxins in suspended material
      and sediment samples. For each target compound, two selected reaction monitoring
      (SRM) transitions were optimised. Chromatographic conditions were optimised
      considering that the compounds analysed had different chemical structure and
      chromatographic behaviour. Using a Luna C18 column and specific SRM transitions,
      five phytotoxins were resolved. Method detection limits (MDL) for anatoxin-a,
      microcystins RR, LR and YR and okadaic acid were 7.1, 3.3, 81.7, 102.8 and 28.8
      ng g(-1) dry weight in sediment, respectively. The developed analytical method
      was successfully applied to analyse the presence of toxins in suspended solids
      and sediment from Ebro River (NE Spain) and Ebro delta-associated lagoons.
      Anatoxin-a was detected downstream of the Riba-Roja reservoir with levels ranging
      from 20 to 1120 ng g(-1) dry weight of suspended solids. Okadaic acid was only
      detected in three samples collected in the Alfacs Bay (Ebro delta, Spain)
      affected by Dinophysis blooms in 2012. 

PMID- 25619982
TI  - Direct genotyping of C3435T single nucleotide polymorphism in unamplified human
      MDR1 gene using a surface plasmon resonance imaging DNA sensor.
AB  - Optical genotyping of C3435T single nucleotide polymorphisms (SNPs) in
      unamplified human multidrug resistance (MDR1) gene was here performed by a
      surface plasmon resonance imaging (SPRi) dual-targeting DNA assay, allowing its
      selective detection down to 0.18 fM of the whole genomic DNA. The result was
      achieved by the combination of the rational selection of the DNA probe and an
      optimized sample pretreatment (i.e., ultrasound fragmentation and thermal
      denaturation). Some assay developments and tunings were reported in a previously
      published research, but here, for the first time, the biosensor reliability and
      its analytical performance were directly tested on the unamplified human DNA
      extracted from lymphocytes. The assay resulted to be able to differentiate among
      all the possible genotypes of C3435T (homozygote and heterozygote) in the diluted
      genomic samples using a label-free approach and by bypassing the classical PCR
      amplification of the target sequences. Moreover, the reusability of the DNA-based
      chip allowed up to 40 subsequent measuring cycles, opening new horizons in multi
      SNP genotyping based on cheap and daily routine clinical monitoring by optical
      biosensing.

PMID- 25619980
TI  - Xenograft assessment of predictive biomarkers for standard head and neck cancer
      therapies.
AB  - Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to
      treat with overall 5-year survival on the order of 50-60%. Therefore, predictive
      biomarkers for this disease would be valuable to provide more effective and
      individualized therapeutic approaches for these patients. While prognostic
      biomarkers such as p16 expression correlate with outcome; to date, no predictive
      biomarkers have been clinically validated for HNSCC. We generated xenografts in
      immunocompromised mice from six established HNSCC cell lines and evaluated
      response to cisplatin, cetuximab, and radiation. Tissue microarrays were
      constructed from pre- and posttreatment tumor samples derived from each xenograft
      experiment. Quantitative immunohistochemistry was performed using a semiautomated
      imaging and analysis platform to determine the relative expression of five
      potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho
      EGFR, phospho-Akt, phospho-ERK, and excision repair cross-complementation group 1
      (ERCC1). Biomarker levels were compared between xenografts that were sensitive
      versus resistant to a specific therapy utilizing a two-sample t-test with equal
      standard deviations. Indeed the xenografts displayed heterogeneous responses to
      each treatment, and we linked a number of baseline biomarker levels to response.
      This included low ERCC1 being associated with cisplatin sensitivity, low phospho
      Akt correlated with cetuximab sensitivity, and high total EGFR was related to
      radiation resistance. Overall, we developed a systematic approach to identifying
      predictive biomarkers and demonstrated several connections between biomarker
      levels and treatment response. Despite these promising initial results, this work
      requires additional preclinical validation, likely involving the use of patient
      derived xenografts, prior to moving into the clinical realm for confirmation
      among patients with HNSCC. 

PMID- 25619983
TI  - Towards optoelectronic urea biosensors.
AB  - Integration of immobilized enzymes with light-emitting diodes (LEDs) leads to the
      development of optoelectronic enzyme-based biosensors. In this work, urease, used
      as a model enzyme, immobilized in the form of an open-tubular microbioreactor or
      biosensing membrane that has been integrated with two red LEDs. It forms
      complete, fiberless, miniaturized, and extremely economic biooptoelectronic
      devices useful for nonstationary measurements under flow analysis conditions.
      Both enzyme-based biodevices, operating according to the paired emitter detector
      diode (PEDD) principle, allow relatively fast, highly sensitive, and well
      reproducible urea detection in the millimolar range of concentrations. Potential
      analytical applications of the developed urea bioPEDDs have been announced. Both
      presented constructions will be easily adapted for the development of other
      optoelectronic biosensors exploring various enzyme-based schemes of biodetection.

PMID- 25619984
TI  - S1 certification of alpha-endosulfan, beta-endosulfan, and endosulfan sulfate in
      a candidate certified reference material (organochlorine pesticides in tea) by
      isotope dilution gas chromatography-mass spectrometry.
AB  - This paper presents the certification of alpha-endosulfan, beta-endosulfan, and
      endosulfan sulfate in a candidate tea certified reference material (code: GLHK-11
      03) according to the requirements of the ISO Guide 30 series. Certification of
      GLHK-11-03 was based on an analytical method purposely developed for the accurate
      measurement of the mass fraction of the target analytes in the material. An
      isotope dilution mass spectrometry (IDMS) method involving determination by (i)
      gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI-MS) and
      (ii) gas chromatography-electron ionization-high-resolution mass spectrometry (GC
      EI-HRMS) techniques was employed. The performance of the described method was
      demonstrated through participation in the key comparison CCQM-K95 "Mid-Polarity
      Analytes in Food Matrix: Mid-Polarity Pesticides in Tea" organized by the
      Consultative Committee for Amount of Substance-Metrology in Chemistry in 2012,
      where the study material was the same as the certified reference material (CRM).
      The values reported by using the developed method were in good agreement with the
      key comparison reference value (KCRV) assigned for beta-endosulfan (727 +/- 14
      MUg kg(-1)) and endosulfan sulfate (505 +/- 11 MUg kg(-1)), where the degree of
      equivalence (DoE) values were 0.41 and 0.40, respectively. The certified values
      of alpha-endosulfan, beta-endosulfan, and endosulfan sulfate in dry mass fraction
      in GLHK-11-03 were 350, 730, and 502 MUg kg(-1), respectively, and the respective
      expanded uncertainties, due to sample inhomogeneity, long-term and short-term
      stability, and variability in the characterization procedure, were 27 MUg kg(-1)
      (7.8 %), 48 MUg kg(-1) (6.6 %), and 33 MUg kg(-1) (6.6 %). 

PMID- 25619985
TI  - Turn-on sensing for Ag+ based on AIE-active fluorescent probe and cytosine-rich
      DNA.
AB  - An aggregation-induced-emission (AIE)-active molecule, 4,4'-(1E,1'E)-2,2'
      (anthracene-9,10-diyl) bis (ethene-2,1-diyl) bis (N,N,N-trimethylbenzenaminium
      iodide) (DSAI), used as a label-free and turn-on fluorescent probe, was developed
      for Ag(+) sensing. The cytosine-rich DNA (oligo-C) chosen as a base could be
      induced to form a hairpin structure in the presence of Ag(+). To improve the
      sensitivity of Ag(+) detection, we selected nuclease S1 to reduce the
      fluorescence intensity of DSAI via its strong ability to hydrolyze oligo-C. In
      the solution containing oligo-C, DSAI, and nuclease S1, in the absence of Ag(+),
      oligo-C was broken into fragments by nuclease S1; this meant DSAI could not
      aggregate, leading to non-emission of the solution. In the presence of Ag(+),
      oligo-C was induced to form a hairpin structure via the C-Ag(+)-C base pair and
      DSAI could aggregate on the surface of the hairpin structure to produce a strong
      emission. On increasing the amount of Ag(+) in the solution containing oligo-C,
      DSAI, and nuclease S1, the fluorescence intensity of DSAI gradually increased,
      and the highest intensity was nearly 16-fold higher than the original intensity.
      The detection limit at a signal-to-noise ratio (S/N) of 3 was estimated to be 155
      nmol L(-1). The new sensing method provides simplicity, easy operation, and good
      sensitivity and selectivity for Ag(+) detection. 

PMID- 25619986
TI  - Multiresidue analysis of 213 pesticides in leek and garlic using QuEChERS-based
      method and gas chromatography-triple quadrupole mass spectrometry.
AB  - A simple and sensitive multiresidue pesticide analysis method was developed and
      validated for 213 pesticides in leek and garlic based on QuEChERS (quick, easy,
      cheap, effective, rugged, and safe) procedure combined with gas chromatography
      triple quadrupole mass spectrometry. In the QuEChERS method, commercial
      extraction salt packet, dispersive solid-phase extraction adsorbent packet, and
      ceramic homogenizer were used to simplify the extraction procedure. The gas
      chromatography-tandem mass spectrometry (GC-MS/MS) parameters were optimized for
      analysis of 213 pesticides within a 38-min run time with a limit of
      quantification for most of the pesticides at 2 MUg kg(-1). The coefficient of
      determination (r(2)) was >0.99 within the calibration linearity range of 2-400
      MUg kg(-1). Most recoveries at 2, 5, 10, 20, 50, 100, and 200 MUg kg(-1) were in
      the range of 70-120% (n = 6) with associated relative standard deviations (RSDs)
      of <20%, indicating satisfactory precision. Real leek and garlic samples were
      analyzed for method application.

PMID- 25619987
TI  - Analysis of paralytic shellfish toxins using high-field asymmetric waveform ion
      mobility spectrometry with liquid chromatography-mass spectrometry.
AB  - The analysis of paralytic shellfish toxins (PSTs) by liquid chromatography-mass
      spectrometry remains a challenge because of their high polarity, large number of
      analogues and the complex matrix in which they occur. Here we investigate the
      potential utility of high-field asymmetric waveform ion mobility spectrometry
      (FAIMS) as a gas-phase ion separation tool for analysis of PSTs by mass
      spectrometry. We investigate the separation of PSTs using FAIMS with two
      divergent goals: using FAIMS as a primary separation tool for rapid screening by
      electrospray ionization (ESI)-FAIMS-MS or combined with LC in a multidimensional
      LC-ESI-FAIMS-MS separation. First, a survey of the parameters that affect the
      sensitivity and selectivity of PST analysis by FAIMS was carried out using ESI
      FAIMS-MS. In particular, the use of acetonitrile as a gas additive in the carrier
      gas flow offered good separation of all PST epimeric pairs. A second set of FAIMS
      conditions was also identified, which focussed PSTs to a relatively narrow CV
      range allowing development of an LC-ESI-FAIMS-MS method for analysis of PST
      toxins in complex mussel tissue extracts. The quantitative capabilities of this
      method were evaluated by analysing a PST containing mussel tissue matrix
      material. Results compared favourably with analysis by an established LC-post
      column oxidation-fluorescence method with recoveries ranging from 70 to 106%,
      although sensitivity was somewhat reduced. The current work represents the first
      successful separation of PST isomers using ion mobility and shows the promise of
      FAIMS as a tool for analysis of algal biotoxins in complex samples and outlines
      some critical requirements for its future improvement.

PMID- 25619989
TI  - The role of the salience network in processing lexical and nonlexical stimuli in
      cochlear implant users: an ALE meta-analysis of PET studies.
AB  - Previous positron emission tomography (PET) studies have shown that various
      cortical areas are activated to process speech signal in cochlear implant (CI)
      users. Nonetheless, differences in task dimension among studies and low
      statistical power preclude from understanding sound processing mechanism in CI
      users. Hence, we performed activation likelihood estimation meta-analysis of PET
      studies in CI users and normal hearing (NH) controls to compare the two groups.
      Eight studies (58 CI subjects/92 peak coordinates; 45 NH subjects/40 peak
      coordinates) were included and analyzed, retrieving areas significantly activated
      by lexical and nonlexical stimuli. For lexical and nonlexical stimuli, both
      groups showed activations in the components of the dual-stream model such as
      bilateral superior temporal gyrus/sulcus, middle temporal gyrus, left posterior
      inferior frontal gyrus, and left insula. However, CI users displayed additional
      unique activation patterns by lexical and nonlexical stimuli. That is, for the
      lexical stimuli, significant activations were observed in areas comprising
      salience network (SN), also known as the intrinsic alertness network, such as the
      left dorsal anterior cingulate cortex (dACC), left insula, and right
      supplementary motor area in the CI user group. Also, for the nonlexical stimuli,
      CI users activated areas comprising SN such as the right insula and left dACC.
      Previous episodic observations on lexical stimuli processing using the dual
      auditory stream in CI users were reconfirmed in this study. However, this study
      also suggests that dual-stream auditory processing in CI users may need supports
      from the SN. In other words, CI users need to pay extra attention to cope with
      degraded auditory signal provided by the implant.

PMID- 25619988
TI  - Conditional Tat protein brain expression in the GT-tg bigenic mouse induces
      cerebral fractional anisotropy abnormalities.
AB  - Cerebral white matter changes including tissue water diffusion abnormalities
      detected with diffusion tensor magnetic resonance imaging (DTI) are commonly
      found in humans with Human Immunodeficiency Virus (HIV) infection, as well as in
      animal models of the disorder. The severities of some of these abnormalities have
      been reported to correlate with measures of disease progression or severity, or
      with the degree of cognitive dysfunction. Accordingly, DTI may be a useful
      translational biomarker. HIV-Tat protein appears to be an important factor in the
      viral pathogenesis of HIV-associated neurotoxicity. We previously reported
      cerebral gray matter density reductions in the GT-tg bigenic mouse treated with
      doxycycline (Dox) to conditionally induce Tat protein expression. Presently, we
      administered intraperitoneal (i.p.) Dox (100 mg/kg/day) for 7 days to GT-tg mice
      to determine whether induction of conditional Tat expression led to the
      development of cerebral DTI abnormalities. Perfused and fixed brains from eight
      GT-tg mice administered Dox and eight control mice administered saline i.p. were
      extracted and underwent DTI scans on a 9.4 Tesla scanner. A whole brain analysis
      detected fractional anisotropy (FA) reductions in several areas including insular
      and endopiriform regions, as well as within the dorsal striatum. These findings
      suggest that exposure to Tat protein is sufficient to induce FA abnormalities,
      and further support the use of the GT-tg mouse to model some effects of HIV. 

PMID- 25619990
TI  - Directional self-assembly of permanently magnetised nanocubes in quasi two
      dimensional layers.
AB  - To design modern materials with a specific response, the consequences of
      directionally dependent interactions on the self-assembly of constituent
      nanoparticles need to be properly understood. Directionality arises in the study
      of anisometric nanoparticles, where geometry has a drastic effect on the
      properties observed. Given the fact that magnetic interactions are inherently
      anisotropic, if one constructs these particles from a magnetic medium, an
      interesting interplay between the two sources of directionality will occur. We
      have investigated this scenario by exploring systems of dipolar nanocube
      monolayers. Using an applied analytical approach, in combination with molecular
      dynamics simulations, we have determined the ground state structures of
      individual monolayer clusters. Taking inspiration from experiments, two different
      fixed dipole orientations for the permanent magnetisation of the nanocubes were
      considered: the first aligned along the [001] crystallographic axis of each cube,
      and the second along the [111] axis. We discovered that the structure of the
      ground state is distinctly different for the two systems of permanently
      magnetised nanocubes; [001] cubes form dipolar chains in the ground state,
      whereas those with [111] orientation adopt square lattice structures. The
      discovered configurations in the ground state represent two different structural
      motifs, as yet unobserved in the ground state of other magnetic nanoparticle
      systems. 

PMID- 25619992
TI  - Polymeric ionic liquid and carbon black composite as a reusable supporting
      electrolyte: modification of the electrode surface.
AB  - One of the major impediments to using electroorganic synthesis is the need for
      large amounts of a supporting electrolyte to ensure the passage of charge.
      Frequently this causes separation and waste problems. To address these issues, a
      polymeric ionic liquid-Super P carbon black composite has been formulated. The
      system enables electrolyses to be performed without adding an additional
      supporting electrolyte, and its efficient recovery and reuse. In addition, the
      ability of the composite to modify the electrode surface in situ leads to
      improved kinetics. A practical consequence is that one can decrease catalyst
      loading without sacrificing efficiency. 

PMID- 25619991
TI  - Median Modified Wiener Filter for nonlinear adaptive spatial denoising of protein
      NMR multidimensional spectra.
AB  - Denoising multidimensional NMR-spectra is a fundamental step in NMR protein
      structure determination. The state-of-the-art method uses wavelet-denoising,
      which may suffer when applied to non-stationary signals affected by Gaussian
      white-noise mixed with strong impulsive artifacts, like those in multi
      dimensional NMR-spectra. Regrettably, Wavelet's performance depends on a
      combinatorial search of wavelet shapes and parameters; and multi-dimensional
      extension of wavelet-denoising is highly non-trivial, which hampers its
      application to multidimensional NMR-spectra. Here, we endorse a diverse
      philosophy of denoising NMR-spectra: less is more! We consider spatial filters
      that have only one parameter to tune: the window-size. We propose, for the first
      time, the 3D extension of the median-modified-Wiener-filter (MMWF), an adaptive
      variant of the median-filter, and also its novel variation named MMWF*. We test
      the proposed filters and the Wiener-filter, an adaptive variant of the mean
      filter, on a benchmark set that contains 16 two-dimensional and three-dimensional
      NMR-spectra extracted from eight proteins. Our results demonstrate that the
      adaptive spatial filters significantly outperform their non-adaptive versions.
      The performance of the new MMWF* on 2D/3D-spectra is even better than wavelet
      denoising. Noticeably, MMWF* produces stable high performance almost invariant
      for diverse window-size settings: this signifies a consistent advantage in the
      implementation of automatic pipelines for protein NMR-spectra analysis. 

PMID- 25619993
TI  - The assembly of miRNA-mRNA-protein regulatory networks using high-throughput
      expression data.
AB  - MOTIVATION: Inference of gene regulatory networks from high throughput
      measurement of gene and protein expression is particularly attractive because it
      allows the simultaneous discovery of interactive molecular signals for numerous
      genes and proteins at a relatively low cost. RESULTS: We developed two score
      based local causal learning algorithms that utilized the Markov blanket search to
      identify direct regulators of target mRNAs and proteins. These two algorithms
      were specifically designed for integrated high throughput RNA and protein data.
      Simulation study showed that these algorithms outperformed other state-of-the-art
      gene regulatory network learning algorithms. We also generated integrated miRNA,
      mRNA, and protein expression data based on high throughput analysis of primary
      trophoblasts, derived from term human placenta and cultured under standard or
      hypoxic conditions. We applied the new algorithms to these data and identified
      gene regulatory networks for a set of trophoblastic proteins found to be
      differentially expressed under the specified culture conditions.

PMID- 25619994
TI  - ENVIRONMENTS and EOL: identification of Environment Ontology terms in text and
      the annotation of the Encyclopedia of Life.
AB  - The association of organisms to their environments is a key issue in exploring
      biodiversity patterns. This knowledge has traditionally been scattered, but
      textual descriptions of taxa and their habitats are now being consolidated in
      centralized resources. However, structured annotations are needed to facilitate
      large-scale analyses. Therefore, we developed ENVIRONMENTS, a fast dictionary
      based tagger capable of identifying Environment Ontology (ENVO) terms in text. We
      evaluate the accuracy of the tagger on a new manually curated corpus of 600
      Encyclopedia of Life (EOL) species pages. We use the tagger to associate taxa
      with environments by tagging EOL text content monthly, and integrate the results
      into the EOL to disseminate them to a broad audience of users. AVAILABILITY AND
      IMPLEMENTATION: The software and the corpus are available under the open-source
      BSD and the CC-BY-NC-SA 3.0 licenses, respectively, at
      http://environments.hcmr.gr.

PMID- 25619995
TI  - Bayesian feature selection for high-dimensional linear regression via the Ising
      approximation with applications to genomics.
AB  - MOTIVATION: Feature selection, identifying a subset of variables that are
      relevant for predicting a response, is an important and challenging component of
      many methods in statistics and machine learning. Feature selection is especially
      difficult and computationally intensive when the number of variables approaches
      or exceeds the number of samples, as is often the case for many genomic datasets.
      RESULTS: Here, we introduce a new approach--the Bayesian Ising Approximation
      (BIA)-to rapidly calculate posterior probabilities for feature relevance in L2
      penalized linear regression. In the regime where the regression problem is
      strongly regularized by the prior, we show that computing the marginal posterior
      probabilities for features is equivalent to computing the magnetizations of an
      Ising model with weak couplings. Using a mean field approximation, we show it is
      possible to rapidly compute the feature selection path described by the posterior
      probabilities as a function of the L2 penalty. We present simulations and
      analytical results illustrating the accuracy of the BIA on some simple regression
      problems. Finally, we demonstrate the applicability of the BIA to high
      dimensional regression by analyzing a gene expression dataset with nearly 30 000
      features. These results also highlight the impact of correlations between
      features on Bayesian feature selection. AVAILABILITY AND IMPLEMENTATION: An
      implementation of the BIA in C++, along with data for reproducing our gene
      expression analyses, are freely available at
      http://physics.bu.edu/~pankajm/BIACode.

PMID- 25619996
TI  - protr/ProtrWeb: R package and web server for generating various numerical
      representation schemes of protein sequences.
AB  - Amino acid sequence-derived structural and physiochemical descriptors are
      extensively utilized for the research of structural, functional, expression and
      interaction profiles of proteins and peptides. We developed protr, a
      comprehensive R package for generating various numerical representation schemes
      of proteins and peptides from amino acid sequence. The package calculates eight
      descriptor groups composed of 22 types of commonly used descriptors that include
      about 22 700 descriptor values. It allows users to select amino acid properties
      from the AAindex database, and use self-defined properties to construct
      customized descriptors. For proteochemometric modeling, it calculates six types
      of scales-based descriptors derived by various dimensionality reduction methods.
      The protr package also integrates the functionality of similarity score
      computation derived by protein sequence alignment and Gene Ontology semantic
      similarity measures within a list of proteins, and calculates profile-based
      protein features based on position-specific scoring matrix. We also developed
      ProtrWeb, a user-friendly web server for calculating descriptors presented in the
      protr package. AVAILABILITY AND IMPLEMENTATION: The protr package is freely
      available from CRAN: http://cran.r-project.org/package=protr, ProtrWeb, is freely
      available at http://protrweb.scbdd.com/.

PMID- 25619997
TI  - Cooperative development of logical modelling standards and tools with CoLoMoTo.
AB  - The identification of large regulatory and signalling networks involved in the
      control of crucial cellular processes calls for proper modelling approaches.
      Indeed, models can help elucidate properties of these networks, understand their
      behaviour and provide (testable) predictions by performing in silico experiments.
      In this context, qualitative, logical frameworks have emerged as relevant
      approaches, as demonstrated by a growing number of published models, along with
      new methodologies and software tools. This productive activity now requires a
      concerted effort to ensure model reusability and interoperability between tools.
      Following an outline of the logical modelling framework, we present the most
      important achievements of the Consortium for Logical Models and Tools, along with
      future objectives. Our aim is to advertise this open community, which welcomes
      contributions from all researchers interested in logical modelling or in related
      mathematical and computational developments.

PMID- 25619998
TI  - The molecular basis for histone H4- and H2A-specific amino-terminal acetylation
      by NatD.
AB  - N-terminal acetylation is among the most common protein modifications in
      eukaryotes and is mediated by evolutionarily conserved N-terminal
      acetyltransferases (NATs). NatD is among the most selective NATs; its only known
      substrates are histones H4 and H2A, containing the N-terminal sequence SGRGK in
      humans. Here we characterize the molecular basis for substrate-specific
      acetylation by NatD by reporting its crystal structure bound to cognate
      substrates and performing related biochemical studies. A novel N-terminal segment
      wraps around the catalytic core domain to make stabilizing interactions, and the
      alpha1-alpha2 and beta6-beta7 loops adopt novel conformations to properly orient
      the histone N termini in the binding site. Ser1 and Arg3 of the histone make
      extensive contacts to highly conserved NatD residues in the substrate binding
      pocket, and flanking glycine residues also appear to contribute to substrate
      specific binding by NatD, together defining a Ser-Gly-Arg-Gly recognition
      sequence. These studies have implications for understanding substrate-specific
      acetylation by NAT enzymes.

PMID- 25619999
TI  - Local error estimates dramatically improve the utility of homology models for
      solving crystal structures by molecular replacement.
AB  - Predicted structures submitted for CASP10 have been evaluated as molecular
      replacement models against the corresponding sets of structure factor amplitudes.
      It has been found that the log-likelihood gain score computed for each prediction
      correlates well with common structure quality indicators but is more sensitive
      when the accuracy of the models is high. In addition, it was observed that using
      coordinate error estimates submitted by predictors to weight the model can
      improve its utility in molecular replacement dramatically, and several groups
      have been identified who reliably provide accurate error estimates that could be
      used to extend the application of molecular replacement for low-homology cases. 

PMID- 25620000
TI  - Comparison of Saccharomyces cerevisiae F-BAR domain structures reveals a
      conserved inositol phosphate binding site.
AB  - F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell
      signaling. Although they are generally thought to bind curved membranes
      containing negatively charged phospholipids, numerous functional studies argue
      that differences in lipid-binding selectivities of F-BAR domains are functionally
      important. Here, we compare membrane-binding properties of the Saccharomyces
      cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such
      as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR
      domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We
      determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the
      latter bound to an inositol phosphate. The structures explain phospholipid
      binding selectivity differences and reveal an F-BAR phosphoinositide binding site
      that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained
      in certain other F-BAR domains. Our findings reveal previously unappreciated
      determinants of F-BAR domain lipid-binding specificity and provide a basis for
      its prediction from sequence.

PMID- 25620002
TI  - Fifty years of chasing lizards: new insights advance optimal escape theory.
AB  - Systematic reviews and meta-analyses often examine data from diverse taxa to
      identify general patterns of effect sizes. Meta-analyses that focus on
      identifying generalisations in a single taxon are also valuable because species
      in a taxon are more likely to share similar unique constraints. We conducted a
      comprehensive phylogenetic meta-analysis of flight initiation distance in
      lizards. Flight initiation distance (FID) is a common metric used to quantify
      risk-taking and has previously been shown to reflect adaptive decision-making.
      The past decade has seen an explosion of studies focused on quantifying FID in
      lizards, and, because lizards occur in a wide range of habitats, are ecologically
      diverse, and are typically smaller and differ physiologically from the better
      studied mammals and birds, they are worthy of detailed examination. We found that
      variables that reflect the costs or benefits of flight (being engaged in social
      interactions, having food available) as well as certain predator effects
      (predator size and approach speed) had large effects on FID in the directions
      predicted by optimal escape theory. Variables that were associated with
      morphology (with the exception of crypsis) and physiology had relatively small
      effects, whereas habitat selection factors typically had moderate to large effect
      sizes. Lizards, like other taxa, are very sensitive to the costs of flight. 

PMID- 25620001
TI  - Structural plasticity of helical nanotubes based on coiled-coil assemblies.
AB  - Numerous instances can be seen in evolution in which protein quaternary
      structures have diverged while the sequences of the building blocks have remained
      fairly conserved. However, the path through which such divergence has taken place
      is usually not known. We have designed two synthetic 29-residue alpha-helical
      peptides, based on the coiled-coil structural motif, that spontaneously self
      assemble into helical nanotubes in vitro. Using electron cryomicroscopy with a
      newly available direct electron detection capability, we can achieve near-atomic
      resolution of these thin structures. We show how conservative changes of only one
      or two amino acids result in dramatic changes in quaternary structure, in which
      the assemblies can be switched between two very different forms. This system
      provides a framework for understanding how small sequence changes in evolution
      can translate into very large changes in supramolecular structure, a phenomenon
      that may have significant implications for the de novo design of synthetic
      peptide assemblies.

PMID- 25620003
TI  - Natural abundance 15N NMR by dynamic nuclear polarization: fast analysis of
      binding sites of a novel amine-carboxyl-linked immobilized dirhodium catalyst.
AB  - A novel heterogeneous dirhodium catalyst has been synthesized. This stable
      catalyst is constructed from dirhodium acetate dimer (Rh2(OAc)4) units, which are
      covalently linked to amine- and carboxyl-bifunctionalized mesoporous silica (SBA
      15-NH2-COOH). It shows good efficiency in catalyzing the cyclopropanation
      reaction of styrene and ethyl diazoacetate (EDA) forming cis- and trans-1
      ethoxycarbonyl-2-phenylcyclopropane. To characterize the structure of this
      catalyst and to confirm the successful immobilization, heteronuclear solid-state
      NMR experiments have been performed. The high application potential of dynamic
      nuclear polarization (DNP) NMR for the analysis of binding sites in this novel
      catalyst is demonstrated. Signal-enhanced (13)C CP MAS and (15)N CP MAS
      techniques have been employed to detect different carboxyl and amine binding
      sites in natural abundance on a fast time scale. The interpretation of the
      experimental chemical shift values for different binding sites has been
      corroborated by quantum chemical calculations on dirhodium model complexes.

PMID- 25620004
TI  - Flexibility in the N-terminal actin-binding domain: clues from in silico
      mutations and molecular dynamics.
AB  - Dystrophin is a long, rod-shaped cytoskeleton protein implicated in muscular
      dystrophy (MDys). Utrophin is the closest autosomal homolog of dystrophin. Both
      proteins have N-terminal actin-binding domain (N-ABD), a central rod domain and C
      terminal region. N-ABD, composed of two calponin homology (CH) subdomains joined
      by a helical linker, harbors a few disease causing missense mutations. Although
      the two proteins share considerable homology (>72%) in N-ABD, recent structural
      and biochemical studies have shown that there are significant differences
      (including stability, mode of actin-binding) and their functions are not
      completely interchangeable. In this investigation, we have used extensive
      molecular dynamics simulations to understand the differences and the similarities
      of these two proteins, along with another actin-binding protein, fimbrin. In
      silico mutations were performed to identify two key residues that might be
      responsible for the dynamical difference between the molecules. Simulation points
      to the inherent flexibility of the linker region, which adapts different
      conformations in the wild type dystrophin. Mutations T220V and G130D in
      dystrophin constrain the flexibility of the central helical region, while in the
      two known disease-causing mutants, K18N and L54R, the helicity of the region is
      compromised. Phylogenetic tree and sequence analysis revealed that dystrophin and
      utrophin genes have probably originated from the same ancestor. The investigation
      would provide insight into the functional diversity of two closely related
      proteins and fimbrin, and contribute to our understanding of the mechanism of
      MDys.

PMID- 25620005
TI  - Robust methods to create ex vivo minimum deformation atlases for brain mapping.
AB  - Highly detailed ex vivo 3D atlases of average structure are of critical
      importance to neuroscience and its current push to understanding the global
      microstructure of the brain. Multiple single slice histology sections can no
      longer provide sufficient detail of inter-slice microstructure and lack out of
      plane resolution. Two ex vivo methods have emerged that can create such detailed
      models. High-field micro MRI with the addition of contrast media has allowed
      intact whole brain microstructure imaging with an isotropic resolution of 15 MUm
      in mouse. Blockface imaging has similarly evolved to a point where it is now
      possible to image an entire brain in a rigorous fashion with an out of plane
      resolution of 10 MUm. Despite the destruction of the tissue as part of this
      process it allows a reconstructed model that is free from cutting artifacts. Both
      of these methods have been utilised to create minimum deformation atlases that
      are representative of the respective populations. The MDA atlases allow us
      unprecedented insight into the commonality and differences in microstructure in
      cortical structures in specific taxa. In this paper we provide an overview of how
      to create such MDA models from ex vivo data.

PMID- 25620006
TI  - Physical methods for gene transfer.
AB  - The key impediment to the successful application of gene therapy in clinics is
      not the paucity of therapeutic genes. It is rather the lack of nontoxic and
      efficient strategies to transfer therapeutic genes into target cells. Over the
      past few decades, considerable progress has been made in gene transfer
      technologies, and thus far, three different delivery systems have been developed
      with merits and demerits characterizing each system. Viral and chemical methods
      of gene transfer utilize specialized carrier to overcome membrane barrier and
      facilitate gene transfer into cells. Physical methods, on the other hand, utilize
      various forms of mechanical forces to enforce gene entry into cells. Starting in
      1980s, physical methods have been introduced as alternatives to viral and
      chemical methods to overcome various extra- and intracellular barriers that limit
      the amount of DNA reaching the intended cells. Accumulating evidence suggests
      that it is quite feasible to directly translocate genes into cytoplasm or even
      nuclei of target cells by means of mechanical force, bypassing endocytosis, a
      common pathway for viral and nonviral vectors. Indeed, several methods have been
      developed, and the majority of them share the same underlying mechanism of gene
      transfer, i.e., physically created transient pores in cell membrane through which
      genes get into cells. Here, we provide an overview of the current status and
      future research directions in the field of physical methods of gene transfer. 

PMID- 25620007
TI  - Nonviral gene delivery systems by the combination of bubble liposomes and
      ultrasound.
AB  - The combination of therapeutic ultrasound (US) and nano/microbubbles is an
      important system for establishing a novel and noninvasive gene delivery system.
      Genes are delivered more efficiently using this system compared with a
      conventional nonviral vector system such as the lipofection method, resulting in
      higher gene expression. This higher efficiency is due to the gene being delivered
      into the cytosol and bypassing the endocytosis pathway. Many in vivo studies have
      demonstrated US-mediated gene delivery with nano/microbubbles, and several gene
      therapy feasibility studies for various diseases have been reported. In addition,
      nano/microbubbles can deliver genes site specifically by the control of US
      exposure site. In the present review, we summarize the gene delivery systems by
      the combination of nano/microbubbles and US, describe their properties, and
      assess applications and challenges of US theranostics. 

PMID- 25620009
TI  - Hydrodynamic delivery.
AB  - Hydrodynamic delivery (HD) is a broadly used procedure for DNA and RNA delivery
      in rodents, serving as a powerful tool for gene/protein drug discovery, gene
      function analysis, target validation, and identification of elements in
      regulating gene expression in vivo. HD involves a pressurized injection of a
      large volume of solution into a vasculature. New procedures are being developed
      to satisfy the need for a safe and efficient gene delivery in clinic. Here, we
      summarize the fundamentals of HD, its applications, and future perspectives for
      clinical use. 

PMID- 25620010
TI  - Sustained expression from DNA vectors.
AB  - DNA vectors have the potential to become powerful medical tools for treatment of
      human disease. The human body has, however, developed a range of defensive
      strategies to detect and silence foreign or misplaced DNA, which is more
      typically encountered during infection or chromosomal damage. A clinically
      relevant human gene therapy vector must overcome or avoid these protections
      whilst delivering sustained levels of therapeutic gene product without
      compromising the vitality of the recipient host. Many non-viral DNA vectors
      trigger these defense mechanisms and are subsequently destroyed or rendered
      silent. Thus, without modification or considered design, the clinical utility of
      a typical DNA vector is fundamentally limited due to the transient nature of its
      transgene expression. The development of safe and persistently expressing DNA
      vectors is a crucial prerequisite for its successful clinical application and
      subsequently remains, therefore, one of the main strategic tasks of non-viral
      gene therapy research. In this chapter we will describe our current understanding
      of the mechanisms that can destroy or silence DNA vectors and discuss strategies,
      which have been utilized to improve their sustenance and the level and duration
      of their transgene expression. 

PMID- 25620011
TI  - Noncoding oligonucleotides: the belle of the ball in gene therapy.
AB  - Gene therapy carries the promise of cures for many diseases based on manipulating
      the expression of a person's genes toward the therapeutic goal. The relevance of
      noncoding oligonucleotides to human disease is attracting widespread attention.
      Noncoding oligonucleotides are not only involved in gene regulation, but can also
      be modified into therapeutic tools. There are many strategies that leverage
      noncoding oligonucleotides for gene therapy, including small interfering RNAs,
      antisense oligonucleotides, aptamers, ribozymes, decoys, and bacteriophage phi 29
      RNAs. In this chapter, we will provide a broad, comprehensive overview of gene
      therapies that use noncoding oligonucleotides for disease treatment. The
      mechanism and development of each therapeutic will be described, with a
      particular focus on its clinical development. Finally, we will discuss the
      challenges associated with developing nucleic acid therapeutics and the prospects
      for future success. 

PMID- 25620008
TI  - Electroporation-mediated gene delivery.
AB  - Electroporation has been used extensively to transfer DNA to bacteria, yeast, and
      mammalian cells in culture for the past 30 years. Over this time, numerous
      advances have been made, from using fields to facilitate cell fusion, delivery of
      chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug
      delivery in living tissues from rodents to man. Electroporation uses electrical
      fields to transiently destabilize the membrane allowing the entry of normally
      impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate
      field strengths, the application of these fields to tissues results in little, if
      any, damage or trauma. Indeed, electroporation has even been used successfully in
      human trials for gene delivery for the treatment of tumors and for vaccine
      development. Electroporation can lead to between 100 and 1000-fold increases in
      gene delivery and expression and can also increase both the distribution of cells
      taking up and expressing the DNA as well as the absolute amount of gene product
      per cell (likely due to increased delivery of plasmids into each cell). Effective
      electroporation depends on electric field parameters, electrode design, the
      tissues and cells being targeted, and the plasmids that are being transferred
      themselves. Most importantly, there is no single combination of these variables
      that leads to greatest efficacy in every situation; optimization is required in
      every new setting. Electroporation-mediated in vivo gene delivery has proven
      highly effective in vaccine production, transgene expression, enzyme replacement,
      and control of a variety of cancers. Almost any tissue can be targeted with
      electroporation, including muscle, skin, heart, liver, lung, and vasculature.
      This chapter will provide an overview of the theory of electroporation for the
      delivery of DNA both in individual cells and in tissues and its application for
      in vivo gene delivery in a number of animal models. 

PMID- 25620012
TI  - Self-amplifying mRNA vaccines.
AB  - This chapter provides a brief introduction to nucleic acid-based vaccines and
      recent research in developing self-amplifying mRNA vaccines. These vaccines
      promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and
      safety. The key to realizing the full potential of these vaccines is efficient
      delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and
      express the encoded antigenic protein. The hydrophilicity and strong net negative
      charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic
      complexation with cationic lipids or polymers and physical delivery using
      electroporation or ballistic particles to improve cellular uptake has been
      evaluated. This chapter highlights the rapid progress made in using nonviral
      delivery systems for RNA-based vaccines. Initial preclinical testing of self
      amplifying mRNA vaccines has shown nonviral delivery to be capable of producing
      potent and robust innate and adaptive immune responses in small animals and
      nonhuman primates. Historically, the prospect of developing mRNA vaccines was
      uncertain due to concerns of mRNA instability and the feasibility of large-scale
      manufacturing. Today, these issues are no longer perceived as barriers in the
      widespread implementation of the technology. Currently, nonamplifying mRNA
      vaccines are under investigation in human clinical trials and can be produced at
      a sufficient quantity and quality to meet regulatory requirements. If the
      encouraging preclinical data with self-amplifying mRNA vaccines are matched by
      equivalently positive immunogenicity, potency, and tolerability in human trials,
      this platform could establish nucleic acid vaccines as a versatile new tool for
      human immunization. 

PMID- 25620013
TI  - Gene electrotransfer clinical trials.
AB  - Plasmid or non-viral gene therapy offers an alternative to classic viral gene
      delivery that negates the need for a biological vector. In this case, delivery is
      enhanced by a variety of approaches including lipid or polymer conjugation,
      particle-mediated delivery, hydrodynamic delivery, ultrasound or electroporation.
      Electroporation was originally used as a laboratory tool to deliver DNA to
      bacterial and mammalian cells in culture. Electrode development allowed this
      technique to be modified for in vivo use. After preclinical therapeutic studies,
      clinical delivery of cell impermeant chemotherapeutic agents progressed to
      clinical delivery of plasmid DNA. One huge benefit of this delivery technique is
      its malleability. The pulse protocol used for plasmid delivery can be fine-tuned
      to control the levels and duration of subsequent transgene expression. This fine
      tuning allows transgene expression to be tailored to each therapeutic
      application. Effective and appropriate expression induces the desired clinical
      response that is a critical component for any gene therapy. This chapter focuses
      on clinical trials using in vivo electroporation or electrotransfer as a plasmid
      delivery method. The first clinical trial was initiated in 2004, and now more
      than fifty trials use electric fields for gene delivery. Safety and tolerability
      has been demonstrated by several groups, and early clinical efficacy results are
      promising in both cancer therapeutic and infectious disease vaccine applications.

PMID- 25620014
TI  - Prone 18F-FDG PET/CT changes diagnostic and surgical intervention in a breast
      cancer patient: some considerations about PET/CT imaging acquisition protocol.
AB  - We report a case study demonstrating the value of prone positioning in positron
      emission tomography (PET) of a woman with diagnosed breast cancer (BC) addressed
      to lumpectomy. Surgeon required (18)F-fluorodeoxiglucose ((18)F-FDG) PET study
      for staging and assessment of lymphnode involvement/metastasis prior to
      lumpectomy: a whole-body supine study and a prone acquisition of breast. Supine
      study revealed one lesion, while prone study revealed two lesions. Prone PET
      findings changed diagnosis and therapeutic intervention for patient who was
      subsequently subjected to quadrantectomy. 

PMID- 25620015
TI  - An unexpected double Diels-Alder reaction of (E)-2-bromo-4-aryl-1,3-pentadiene
      involving [1,5]-hydrogen migration and HBr elimination: synthesis of
      bicyclo[2.2.2]octene derivatives.
AB  - An unexpected double Diels-Alder (DDA) reaction of (E)-2-bromo-4-aryl-1,3
      pentadiene was developed and resulted in a series of "butterfly-like"
      bicyclo[2.2.2]octene derivatives in moderate to good yields without the need for
      a metal catalyst. The proposed mechanism involves a [1,5]-sigmatropic hydrogen
      migration and HBr elimination. Through this decisive [1,5]-hydrogen shift step,
      the electronic properties and steric hindrance of the conjugated diene substrate
      are completely altered and the DDA reaction of this potential diene synthon is
      successfully achieved. 

PMID- 25620017
TI  - Central arteriovenous anastomosis in resistant hypertension?

PMID- 25620018
TI  - Novel multiplex format of an extended multilocus variable-number-tandem-repeat
      analysis of Clostridium difficile correlates with tandem repeat sequence typing.
AB  - Subtyping of Clostridium difficile is crucial for outbreak investigations. An
      extended multilocus variable-number tandem-repeat analysis (eMLVA) of 14 variable
      number tandem repeat (VNTR) loci was validated in multiplex format compatible
      with a routine typing laboratory and showed excellent concordance with tandem
      repeat sequence typing (TRST) and high discriminatory power. 

PMID- 25620016
TI  - Central arteriovenous anastomosis for the treatment of patients with uncontrolled
      hypertension (the ROX CONTROL HTN study): a randomised controlled trial.
AB  - BACKGROUND: Hypertension contributes to cardiovascular morbidity and mortality.
      We assessed the safety and efficacy of a central iliac arteriovenous anastomosis
      to alter the mechanical arterial properties and reduce blood pressure in patients
      with uncontrolled hypertension. METHODS: We enrolled patients in this open-label,
      multicentre, prospective, randomised, controlled trial between October, 2012, and
      April, 2014. Eligible patients had baseline office systolic blood pressure of 140
      mm Hg or higher and average daytime ambulatory blood pressure of 135 mm Hg or
      higher systolic and 85 mm Hg or higher diastolic despite antihypertensive
      treatment. Patients were randomly allocated in a 1:1 ratio to undergo
      implantation of an arteriovenous coupler device plus current pharmaceutical
      treatment or to maintain current treatment alone (control). The primary endpoint
      was mean change from baseline in office and 24 h ambulatory systolic blood
      pressure at 6 months. Analysis was by modified intention to treat (all patients
      remaining in follow-up at 6 months). This trial is registered with
      ClinicalTrials.gov, number NCT01642498. FINDINGS: 83 (43%) of 195 patients
      screened were assigned arteriovenous coupler therapy (n=44) or normal care
      (n=39). Mean office systolic blood pressure reduced by 26.9 (SD 23.9) mm Hg in
      the arteriovenous coupler group (p<0.0001) and by 3.7 (21.2) mm Hg in the control
      group (p=0.31). Mean systolic 24 h ambulatory blood pressure reduced by 13.5
      (18.8) mm Hg (p<0.0001) in arteriovenous coupler recipients and by 0.5 (15.8) mm
      Hg (p=0.86) in controls. Implantation of the arteriovenous coupler was associated
      with late ipsilateral venous stenosis in 12 (29%) of 42 patients and was
      treatable with venoplasty or stenting. INTERPRETATION: Arteriovenous anastomosis
      was associated with significantly reduced blood pressure and hypertensive
      complications. This approach might be a useful adjunctive therapy for patients
      with uncontrolled hypertension. FUNDING: ROX Medical.

PMID- 25620019
TI  - Effects of bacterial inactivation methods on downstream proteomic analysis.
AB  - Inactivation of pathogenic microbial samples is often necessary for the
      protection of researchers and to comply with local and federal regulations. By
      its nature, biological inactivation causes changes to microbial samples,
      potentially affecting observed experimental results. While inactivation-induced
      damage to materials such as DNA has been evaluated, the effect of various
      inactivation strategies on proteomic data, to our knowledge, has not been
      discussed. To this end, we inactivated samples of Yersinia pestis and Escherichia
      coli by autoclave, ethanol, or irradiation treatment to determine how
      inactivation changes liquid chromatography-tandem mass spectrometry data quality
      as well as apparent protein content of cells. Proteomic datasets obtained from
      aliquots of samples inactivated by different methods were highly similar, with
      Pearson correlation coefficients ranging from 0.822 to 0.985 and 0.816 to 0.985
      for E. coli and Y. pestis, respectively, suggesting that inactivation had only
      slight impacts on the set of proteins identified. In addition, spectral quality
      metrics such as distributions of various database search algorithm scores
      remained constant across inactivation methods, indicating that inactivation does
      not appreciably degrade spectral quality. Though overall changes resulting from
      inactivation were small, there were detectable trends. For example, one-sided
      Fischer exact tests determined that periplasmic proteins decrease in observed
      abundance after sample inactivation by autoclaving (alpha=1.71*10(-2) for E.
      coli, alpha=4.97*10(-4) for Y. pestis) and irradiation (alpha=9.43*10(-7) for E.
      coli, alpha=1.21*10(-5) for Y. pestis) when compared to controls that were not
      inactivated. Based on our data, if sample inactivation is necessary, we recommend
      inactivation with ethanol treatment with secondary preference given to
      irradiation. 

PMID- 25620020
TI  - [Role of acetylsalicylic acid for preventing recurrent venous thromboembolism].

PMID- 25620021
TI  - Multiple sclerosis (MS) for the urologist: What should urologists know about MS?
AB  - Multiple sclerosis (MS) is a unique central nervous system (CNS) inflammatory
      disease with a broad spectrum of clinical presentations, which are time- and
      disease progression-related. It usually affects young adults, with a female
      predominance of 3:1. Men are more likely to develop symptoms at a slightly older
      age with a more progressive disease course. Diagnosis relies on a combination of
      clinical, radiological, and laboratory investigations, with a central role of
      magnetic resonance imaging (MRI). Although the exact etiology is still obscure,
      the leading hypothesis behind MS relapses is acute inflammatory attacks on CNS
      myelin and axons. This complex process involves B and T cells together with
      macrophages and microglia. Genetic and environmental factors are thought to be
      major contributors to the disease's evolution. MS therapies consist of long-term
      (immunomodulatory) management, focusing on disease modification, and short-term
      symptomatic control. Symptomatic treatment includes pharmacological and non
      pharmacological methods to protect function and restore quality of life (QoL).
      The introduction and development of disease-modifying medications provide
      opportunities to change the face of this disease, enhancing QoL over the long
      term. Interferon (INF) and Glatiramer acetate (GLAT) represent first line
      medications with limited effect and relatively fair safety profile. Newer
      medications with improved efficacy along with a more hazardous side effect
      profile are now considered second line therapy. CONCLUSIONS: The present review
      summarizes current knowledge of this frequent disease. Urologists must acquire a
      deeper understanding for better integration of practice recommendations.

PMID- 25620022
TI  - Expression and intracytoplasmic distribution of staufen and calreticulin in
      maturing human oocytes.
AB  - PURPOSE: In this study we hypothesized that the mRNA vector Staufen mediates RNA
      relocalization during meiotic maturation, and by virtue of its interactions with
      endoplasmic reticulum, provides a possible mechanism by which protein synthesis
      is regulated. METHODS: We assessed the expression of staufen (STAU) and
      calreticulin (CALR), the latter adopted as a marker of the endoplasmic reticulum,
      in human oocytes at different stages of maturation: GV, metaphase MI and MII.
      Oocytes were subjected to polymerase chain reaction in order to investigate the
      expression of STAU and CALR. The corresponding protein products were identified
      by immunofluorescence and confocal laser scanning microscopy. RESULTS: STAU and
      CALR were constantly expressed and selectively localized during oocyte
      maturation. At the GV stage the both proteins displayed a dispersed distribution
      localization throughout the cytoplasm. Progressing to the MII stage, STAU tended
      to compartmentalize towards the cortical area of the oocyte clustering in
      granules of larger sizes. At the MII stage, CALR assumed a pattern reminiscent
      and possibly coincident with the position of the meiotic spindle. CONCLUSIONS:
      The changing pattern of STAU distribution during meiotic maturation of human
      oocytes implicates a novel mechanism for the regulation of protein synthesis
      based on mRNA localization. Moreover, the unique disposition of CALR at the MII
      spindle uncovers a physical interaction with endoplasmic reticulum that may
      mediate cytoskeletal remodelling during oocyte maturation.

PMID- 25620023
TI  - Thalidomide Inhibits Adhesion Molecules in Experimental Acute Pancreatitis
      Associated Lung Injury.
AB  - Preclinical Research The study evaluated the effect of thalidomide on adhesion
      molecule expression in acute pancreatitis-associated lung injury in rats. Acute
      pancreatitis was induced in rats by retrograde infusion of 5% sodium taurocholate
      into the bile-pancreatic duct, and thalidomide (100 mg/kg) was given daily by
      intragastric route for 8 days before this treatment. Serum lipase (LPS), protein
      levels in bronchoalveolar lavage fluid (BALF), superoxide dismutase (SOD),
      glutathione peroxidase (GSHpx), and malondialdehyde (MDA) levels in lung were
      measured. Compared with the acute pancreatitis- group, lung histopathology, serum
      LPS, protein levels in BALF, SOD, GSHpx, and MDA levels, and the expression
      levels of intercellular adhesion molecule-1 and E-selectin mRNA and protein in
      rats given thalidomide were improved (P < 0.01). Thus, thalidomide may reduce the
      expression of adhesion molecules via inhibition of oxidative stress to alleviate
      acute pancreatitis-associated lung injury in a rat model. Drug Dev Res, 2014. (c)
      2014 Wiley Periodicals, Inc.

PMID- 25620024
TI  - ENO2 activity is required for the development and reproductive success of plants,
      and is feedback-repressed by AtMBP-1.
AB  - Enolases are key glycolytic enzymes that are highly conserved in prokaryotic and
      eukaryotic organisms, and are among the most abundant cytosolic proteins. In this
      study we provide evidence that activity of the enolase ENO2 is essential for the
      growth and development of plants. We show that Arabidopsis plants with
      compromised ENO2 function, which were generated by mutating the LOS2/ENO2 locus,
      have severe cellular defects, including reduced cell size and defective cell
      differentiation with restricted lignification. At the tissue and organ level
      LOS2/ENO2-deficient plants are characterized by the reduced growth of shoots and
      roots, altered vascular development and defective secondary growth of stems,
      impaired floral organogenesis and defective male gametophyte function, resulting
      in embryo lethality as well as delayed senescence. These phenotypes correlate
      with reduced lignin and increased salicylic acid contents as well as altered
      fatty acid and soluble sugar composition. In addition to an enolase the LOS2/ENO2
      locus encodes the transcription factor AtMBP-1, and here we reveal that this
      bifunctionality serves to maintain the homeostasis of ENO2 activity. In summary,
      we show that in plants enolase function is required for the formation of
      chorismate-dependent secondary metabolites, and that this activity is feedback
      inhibited by AtMBP-1 to enable the normal development and reproductive success of
      plants. 

PMID- 25620025
TI  - [Clinical interpretation of high sensitivity troponin T].
AB  - Determination of cardiac troponin (cTn) is necessary for the diagnosis of acute
      myocardial infarction without ST segment elevation. However Tnc can be released
      in other clinical situations. The development of high-sensitive cTn T assays (hs
      cTnT) improves the management of patients with suspected acute coronary syndrome.
      Here, we provide an overview of the diverse causes of hs-cTnT elevation and
      recommend strategies for the clinical interpretation of the test result. 

PMID- 25620026
TI  - Simultaneous determination of three herbicides in wheat, wheat straw, and soil
      using a quick, easy, cheap, effective, rugged, and safe method with ultra high
      performance liquid chromatography and tandem mass spectrometry.
AB  - In this study, a sensitive and effective analytical method for the extraction and
      detection of three herbicide residues (florasulam, fluroxypyr, and halauxifen
      methyl) in wheat and soil was developed. Samples were extracted with
      acetonitrile/water followed by salting out, dispersive solid-phase extraction
      cleanup, and detection using ultra high performance liquid chromatography coupled
      with tandem mass spectrometry. The target analytes were detected within a 5 min
      runtime using an ultra high performance liquid chromatography high-strength
      silica trifunctional column connected to an electrospray ionization source in
      positive mode. The method was validated in five replicates at three fortification
      concentrations in each matrix. Adequate pesticide quantification and identity
      confirmation were attained, even at the lowest concentration levels. The method
      showed very good accuracy and precision. Good recoveries were observed for the
      three herbicides and mostly ranged between 75.8 and 114.6%, with intraday
      relative standard deviations <6.01% and interday relative standard deviations
      <4.02%. The limits of quantification ranged between 0.14 and 7.68 MUg/kg for each
      herbicide. The method was successfully applied for the simultaneous analysis of
      the three herbicides in actual trial samples, and the results proved that the
      proposed method was effective in detecting these three herbicides. 

PMID- 25620027
TI  - Reply to the correspondence letter by Szarpak L et al. "Can Glidescope(r)
      videolaryngoscope be an alternative to direct laryngoscopy for child and infant
      tracheal intubation during chest compression?".

PMID- 25620028
TI  - Effectiveness and safety of the posterior approach with soft tissue repair for
      primary total hip arthroplasty: a meta-analysis.
AB  - BACKGROUND: Repair of soft tissue in favour of the posterior approach for total
      hip arthroplasty is still under discussion and few studies are assessing this
      issue. Therefore, we performed a meta-analysis to compare the effectiveness and
      safety of the posterior approach for total hip arthroplasty with and without soft
      tissue repair. We focused on these questions as follows: does primary posterior
      approach for total hip arthroplasty with soft tissue repair has better result
      regarding dislocation rate, Harris hip score and the sciatic nerve palsy rate
      compared with posterior approach without soft tissue repair. PATIENTS AND
      METHODS: We conducted electronic literature searches using CENTRAL (Issue 1 of
      12, Jan 2014), PUBMED (1980 to Jan 2014), and EMBASE (1980 to Jan 2014). Clinical
      studies evaluating the posterior approach for total hip arthroplasty with and
      without soft tissue repair were collected. After independent study selection by 2
      authors, data were collected and extracted independently. The methodological
      quality of the studies was assessed by the Cochrane Collaboration's tool for
      assessing risk of bias and the Newcastle-Ottawa Scale. RESULT: Seven clinical
      trials with 4594 hips using the posterior approach for total hip arthroplasty
      were included. The pooled data indicated a lower rate of dislocation (OR: 0.14,
      95% CI: 0.08-0.26, P<0.00001) and higher Harris hip score (1.75, 95% CI: 1.19 to
      2.32, P<0.00001, I(2)=26%) after the posterior approach to total hip arthroplasty
      using soft tissue repair than without using soft tissue repair. There was no
      statistical difference in sciatic nerve palsy between the use of soft tissue
      repair and without it in posterior approach to total hip arthroplasty (OR: 5.34,
      95% CI: 0.25-112.25, P=0.28). DISCUSSION: Our meta-analysis included data from
      more studies than were previously available and demonstrated that the use of soft
      tissue repair and without it in posterior approach to total hip arthroplasty are
      similar in safety. Using repair resulted in a lower dislocation rate and higher
      Harris hip score than without repair. LEVELS OF EVIDENCE: Level 2 meta-analysis
      of low-powered prospective randomised trial.

PMID- 25620029
TI  - Adverse tissue reaction to corrosion at the neck-stem junction after modular
      primary total hip arthroplasty.
AB  - Complications related to the neck-stem junction of modular stems used for total
      hip arthroplasty (THA) are generating increasing concern. A 74-year-old male had
      increasing pain and a cutaneous reaction around the scar 1 year after THA with a
      modular neck-stem. Imaging revealed osteolysis of the calcar and a pseudo-tumour
      adjacent to the neck-stem junction. Serum cobalt levels were elevated. Revision
      surgery to exchange the stem and liner and to resect the pseudo-tumour was
      performed. Analysis of the stem by scanning electron microscopy and by energy
      dispersive X-ray and white light interferometry showed fretting corrosion at the
      neck-stem junction contrasting with minimal changes at the head-neck junction.
      Thus, despite dry assembly of the neck and stem on the back table at primary THA,
      full neck-stem contact was not achieved, and the resulting micromotion at the
      interface led to fretting corrosion. This case highlights the mechanism of
      fretting corrosion at the neck-stem interface responsible for adverse local
      tissue reactions. Clinical and radiological follow-up is mandatory in patients
      with dual-modular stems. 

PMID- 25620031
TI  - Validation of two accelerometers to determine mechanical loading of physical
      activities in children.
AB  - The purpose of this study was to assess the validity of accelerometers using
      force plates (i.e., ground reaction force (GRF)) during the performance of
      different tasks of daily physical activity in children. Thirteen children (10.1
      (range 5.4-15.7) years, 3 girls) wore two accelerometers (ActiGraph GT3X+ (ACT),
      GENEA (GEN)) at the hip that provide raw acceleration signals at 100 Hz.
      Participants completed different tasks (walking, jogging, running, landings from
      boxes of different height, rope skipping, dancing) on a force plate. GRF was
      collected for one step per trial (10 trials) for ambulatory movements and for all
      landings (10 trials), rope skips and dance procedures. Accelerometer outputs as
      peak loading (g) per activity were averaged. ANOVA, correlation analyses and
      Bland-Altman plots were computed to determine validity of accelerometers using
      GRF. There was a main effect of task with increasing acceleration values in tasks
      with increasing locomotion speed and landing height (P < 0.001). Data from ACT
      and GEN correlated with GRF (r = 0.90 and 0.89, respectively) and between each
      other (r = 0.98), but both accelerometers consistently overestimated GRF. The new
      generation of accelerometer models that allow raw signal detection are reasonably
      accurate to measure impact loading of bone in children, although they
      systematically overestimate GRF. 

PMID- 25620030
TI  - Glutathione and thioredoxin antioxidant pathways synergize to drive cancer
      initiation and progression.
AB  - Controversy over the role of antioxidants in cancer has persisted for decades.
      Here, we demonstrate that synthesis of the antioxidant glutathione (GSH), driven
      by GCLM, is required for cancer initiation. Genetic loss of Gclm prevents a
      tumor's ability to drive malignant transformation. Intriguingly, these findings
      can be replicated using an inhibitor of GSH synthesis, but only if delivered
      prior to cancer onset, suggesting that at later stages of tumor progression GSH
      becomes dispensable potentially due to compensation from alternative antioxidant
      pathways. Remarkably, combined inhibition of GSH and thioredoxin antioxidant
      pathways leads to a synergistic cancer cell death in vitro and in vivo,
      demonstrating the importance of these two antioxidants to tumor progression and
      as potential targets for therapeutic intervention. 

PMID- 25620032
TI  - Reliability and validity of the Head and Neck Cancer Inventory (HNCI) in Japanese
      patients.
AB  - OBJECTIVE: This project evaluated the psychometric properties of a translated
      version of the Head and Neck Cancer Inventory (HNCI) for use with Japanese
      patients. The HNCI is a measure for assessing the quality of life (QoL) of head
      and neck cancer patients and survivors. The present study was aimed at
      investigating the reliability and validity of this translated instrument. METHOD:
      Some 165 patients with head and neck cancer (HNC) were enrolled at the Tokyo
      Medical and Dental University Hospital. The instrument's internal consistency and
      test-retest reliability were evaluated. Criterion-related validity was assessed
      by correlations between the HNCI and the Functional Assessment of Cancer Therapy
      Head and Neck (FACT-H&N) scales. RESULTS: Some 29 of the 30 items in the original
      version were selected to comprise the Japanese version of the HNCI (Japanese
      HNCI). Investigation of criterion-related validity using the FACT-H&N
      demonstrated significant correlations (Spearman's rho = 0.47-0.63). The value of
      Cronbach's alpha for each subscale ranged from 0.84 to 0.87. Test-retest
      reliability showed an intraclass correlation coefficient (ICC) of 0.62-0.79.
      SIGNIFICANCE OF RESULTS: The reliability and validity of the Japanese HNCI were
      evaluated. Although its classification is different from the original U.S.
      version, the Japanese HNCI is a self-administered questionnaire that can assess
      quality of life (QoL) in patients with head and neck cancer.

PMID- 25620033
TI  - Geometry of the magic number H(+)(H2O)21 water cluster by proxy.
AB  - Abundance mass spectra, obtained upon carefully electrospraying solutions of tert
      butanol (TB) in water into a mass spectrometer, display a systematic series of
      peaks due to mixed H(+)(TB)m(H2O)n clusters. Clusters with m + n = 21 have higher
      abundance (magic number peaks) than their neighbours when m <= 9, while for m > 9
      they have lower abundance. This indicates that the mixed TB-H2O clusters retain a
      core hydrogen bonded network analogous to that in the famous all-water
      H(+)(H2O)21 cluster up to the limit m = 9. The limiting value corresponds to the
      number of dangling O-H groups pointing out from the surface of the degenerated
      pentagonal dodecahedral, considered to be the lowest energy form of H(+)(H2O)21;
      the experimental findings therefore support this geometry. The experimental
      findings are supported by ab initio quantum chemical calculations to provide a
      consistent framework for the interpretation of these kinds of experiments. 

PMID- 25620034
TI  - Deep breathing exercises with positive expiratory pressure in patients with
      multiple sclerosis - a randomized controlled trial.
AB  - INTRODUCTION: Breathing exercises with positive expiratory pressure are often
      recommended to patients with advanced neurological deficits, but the potential
      benefit in multiple sclerosis (MS) patients with mild and moderate symptoms has
      not yet been investigated in randomized controlled trials. OBJECTIVES: To study
      the effects of 2 months of home-based breathing exercises for patients with mild
      to moderate MS on respiratory muscle strength, lung function, and subjective
      breathing and health status outcomes. METHODS: Forty-eight patients with MS
      according to the revised McDonald criteria were enrolled in a randomized
      controlled trial. Patients performing breathing exercises (n = 23) were compared
      with a control group (n = 25) performing no breathing exercises. The breathing
      exercises were performed with a positive expiratory pressure device (10-15 cmH2
      O) and consisted of 30 slow deep breaths performed twice a day for 2 months.
      Respiratory muscle strength (maximal inspiratory and expiratory pressure at the
      mouth), spirometry, oxygenation, thoracic excursion, subjective perceptions of
      breathing and self-reported health status were evaluated before and after the
      intervention period. RESULTS: Following the intervention, there was a significant
      difference between the breathing group and the control group regarding the
      relative change in lung function, favoring the breathing group (vital capacity: P
      < 0.043; forced vital capacity: P < 0.025). There were no other significant
      differences between the groups. CONCLUSION: Breathing exercises may be beneficial
      in patients with mild to moderate stages of MS. However, the clinical
      significance needs to be clarified, and it remains to be seen whether a
      sustainable effect in delaying the development of respiratory dysfunction in MS
      can be obtained.

PMID- 25620035
TI  - Prodifferentiation, anti-inflammatory and antiproliferative effects of
      delphinidin, a dietary anthocyanidin, in a full-thickness three-dimensional
      reconstituted human skin model of psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disorder of skin and joints for
      which conventional treatments that are effective in clearing the moderate-to
      severe disease are limited due to long-term safety issues. This necessitates
      exploring the usefulness of botanical agents for treating psoriasis. We
      previously showed that delphinidin, a diet-derived anthocyanidin endowed with
      antioxidant and anti-inflammatory properties, induces normal epidermal
      keratinocyte differentiation and suggested its possible usefulness for the
      treatment of psoriasis [1]. OBJECTIVES: To investigate the effect of delphinidin
      (0-20 MUM; 2-5 days) on psoriatic epidermal keratinocyte differentiation,
      proliferation and inflammation using a three-dimensional reconstructed human
      psoriatic skin equivalent (PSE) model. METHODS: PSEs and normal skin equivalents
      (NSEs) established on fibroblast-contracted collagen gels with respective
      psoriatic and normal keratinocytes and treated with/without delphinidin were
      analyzed for histology, expression of markers of differentiation, proliferation
      and inflammation using histomorphometry, immunoblotting, immunochemistry, qPCR
      and cultured supernatants for cytokine with a Multi-Analyte ELISArray Kit.
      RESULTS: Our data show that treatment of PSE with delphinidin induced (1)
      cornification without affecting apoptosis and (2) the mRNA and protein expression
      of markers of differentiation (caspase-14, filaggrin, loricrin, involucrin). It
      also decreased the expression of markers of proliferation (Ki67 and proliferating
      cell nuclear antigen) and inflammation (inducible nitric oxide synthase and
      antimicrobial peptides S100A7-psoriasin and S100A15-koebnerisin, which are often
      induced in psoriatic skin). ELISArray showed increased release of psoriasis
      associated keratinocyte-derived proinflammatory cytokines in supernatants of the
      PSE cultures, and this increase was significantly suppressed by delphinidin.
      CONCLUSIONS: These observations provide a rationale for developing delphinidin
      for the management of psoriasis.

PMID- 25620036
TI  - Automated breast volume scanning versus conventional ultrasound in breast cancer
      screening.
AB  - RATIONALE AND OBJECTIVES: To assess the diagnostic value of automated breast
      volume scanning (ABVS) versus conventional ultrasound (US) in breast cancer
      screening. MATERIALS AND METHODS: This study retrospectively analyzed the ABVS
      and US images from 200 women who underwent breast examination and were
      recommended for biopsy in our health management centers between July 22, 2011,
      and October 20, 2013. We retrospectively assessed whether breast lesions from 200
      women, which were detected and classified by US, could be detected and classified
      by an independent examiner using only ABVS findings. The sensitivity and
      specificity of ABVS versus US in determining lesion malignancy were calculated
      using biopsy as the gold standard. RESULTS: In the 200 cases, 273 and 194
      individual lesions were detected by ABVS and US, respectively. All 194 US
      detected lesions were detected by ABVS. Pathologic examination determined that,
      of the 273 total lesions, 251 lesions were benign and 22 lesions were malignant.
      US detected 21 of the 22 malignant lesions and ABVS detected all 22 malignant
      lesions. The sensitivity and specificity of ABVS relative to biopsy (gold
      standard) were 28.95% and 100%, whereas the sensitivity and specificity of US
      relative to biopsy were 43.06% and 98.36%. CONCLUSIONS: US displays superior
      sensitivity to ABVS across all Breast Imaging Reporting and Data System (BI-RADS)
      density categories while displaying equivalent specificity with the exception of
      BI-RADS density category 1, in which ABVS displayed a slightly superior
      specificity. As ABVS possesses several advantages and limitations with respect to
      US, ABVS may serve as an effective, adjunct, screening tool to mammography and
      conventional sonography.

PMID- 25620037
TI  - Meta-analysis of net long-term benefit of different therapeutic strategies in
      patients with cryptogenic stroke and patent foramen ovale.
AB  - We pooled available data on follow-up events in patients with patent foramen
      ovale and cryptogenic stroke to evaluate the net clinical benefit of different
      therapeutic strategies (percutaneous closure vs antiplatelet vs anticoagulant
      therapy). MEDLINE/PubMed and Cochrane databases and reviewed cited references to
      identify relevant studies were used; 3,311 patients from 21 clinical studies,
      both observational and randomized, with follow-up >=12 months were overall
      included. Net clinical benefit was evaluated considering the cumulative incidence
      of both stroke and/or transient ischemic attack and major bleeding events.
      Anticoagulant therapy was more effective than antiplatelet therapy in preventing
      recurrent stroke and/or transient ischemic attack (event rates: 7.7% vs 9.8%,
      respectively, p = 0.03), but at the price of more than sixfold greater risk of
      major bleeding (7.1% vs 1.3%; odds ratio 6.49, 95% confidence interval 3.25 to
      12.99, p <0.00001). Patent foramen ovale closure was associated over the long
      term with significant net clinical benefit versus both antiplatelet and
      anticoagulant therapy; such benefit was driven by 50% relative reduction of
      stroke and/or transient ischemic attack versus antiplatelet therapy and by 82%
      relative reduction of major bleeding versus anticoagulant therapy. In conclusion,
      results of this large study-level meta-analysis may influence practice patterns
      in patients with patent foramen ovale and cryptogenic stroke; an individualized
      approach tailored on both the risk of recurrent cerebral events and the bleeding
      risk should be used to identify the best therapeutic option (percutaneous closure
      vs antiplatelet therapy vs anticoagulant therapy).

PMID- 25620038
TI  - Optical coherence tomographic evaluation of the effect of cigarette smoking on
      vascular healing after sirolimus-eluting stent implantation.
AB  - Cigarette smoking is known to be deleterious to patients with coronary artery
      disease; however, the effect of smoking on vascular responses after coronary drug
      eluting stent implantation is unknown. We sought to examine vascular response
      after sirolimus-eluting stent implantation in patients with ongoing smoking using
      optical coherence tomography, compared with former smokers and nonsmokers. We
      identified 181 sirolimus-eluting stents in 140 subjects who underwent follow-up
      optical coherence tomography imaging. Subjects were divided into 3 groups:
      current smokers (n = 28), former smokers (n = 35), and nonsmokers (n = 77). Stent
      strut coverage, neointimal characteristics, and strut malapposition were
      evaluated. The incidence of uncovered stent struts was significantly higher in
      nonsmokers compared with current smokers (13.3 +/- 13.3% vs 6.7 +/- 8.3%; p =
      0.001). On qualitative evaluation of neointimal morphology, the prevalence of
      heterogeneous neointima was higher in current smokers (71.9%) than in former
      smokers (36.0%) or nonsmokers (10.1%) (p = 0.004 and p <0.001, respectively).
      There was no difference in the incidence of malapposition among the 3 groups.
      Multivariate modeling showed that current smoking was negatively associated with
      the presence of uncovered struts (odds ratio 0.33; 95% confidence interval 0.14
      to 0.79; p = 0.013) and positively associated with the presence of heterogeneous
      neointima (odds ratio 9.47; 95% confidence interval 3.79 to 23.72; p <0.001). In
      conclusion, the incidence of strut coverage was higher in current smokers
      compared with nonsmokers. However, the pattern of neointima was more
      heterogeneous in current smokers.

PMID- 25620039
TI  - Comparison of balloon-expandable versus self-expandable valves for transcatheter
      aortic valve implantation in patients with low-gradient severe aortic stenosis
      and preserved left ventricular ejection fraction.
AB  - A relevant proportion of patients, classified as severe aortic stenosis on the
      basis of valve area <=1 cm(2), have a mean transvalvular gradient <=40 mm Hg,
      despite a preserved left ventricular ejection fraction (LGSAS). We assessed the
      clinical and hemodynamic impact of transcatheter aortic valve implantation in
      patients with symptomatic LGSAS at high risk for surgery or inoperable, according
      to the type of percutaneous valve implanted. Ninety-five patients received an
      Edwards SAPIEN valve (Edwards Lifesciences, Irvine, California) and 51 received a
      Medtronic CoreValve (Medtronic, Inc., Minneapolis, Minnesota). The hemodynamic
      performance of the 2 valves was similar in term of final transvalvular gradients
      (10 mm Hg, p = 0.069). Early mortality rate was 7% and was not different between
      the 2 valves (p = 0.73). During follow-up, cardiovascular mortality rate was
      similar between groups, and valve type was not a predictor of outcome (p = 0.72).
      Estimated survival by Kaplan-Meier at 2 years was 70%. At multivariate analysis,
      life-threatening or major bleeding, postprocedural aortic insufficiency, and
      acute kidney injury were the major predictors of an adverse outcome. In patients
      with LGSAS treated by transcatheter aortic valve implantation, the use of balloon
      expandable versus self-expandable valves resulted in similar hemodynamic, early,
      and long-term clinical outcomes. 

PMID- 25620040
TI  - Slow wave sleep in the chronically fatigued: Power spectra distribution patterns
      in chronic fatigue syndrome and primary insomnia.
AB  - OBJECTIVES: To investigate slow wave sleep (SWS) spectral power proportions in
      distinct clinical conditions sharing non-restorative sleep and fatigue complaints
      without excessive daytime sleepiness (EDS), namely the chronic fatigue syndrome
      (CFS) and primary insomnia (PI). Impaired sleep homeostasis has been suspected in
      both CFS and PI. METHODS: We compared perceived sleep quality, fatigue and
      sleepiness symptom-intensities, polysomnography (PSG) and SWS spectral power
      distributions of drug-free CFS and PI patients without comorbid sleep or mental
      disorders, with a good sleeper control group. RESULTS: Higher fatigue without EDS
      and impaired perceived sleep quality were confirmed in both patient groups. PSG
      mainly differed in sleep fragmentation and SWS durations. Spectral analysis
      revealed a similar decrease in central ultra slow power (0.3-0.79Hz) proportion
      during SWS for both CFS and PI and an increase in frontal power proportions of
      faster frequencies during SWS in PI only. The latter was correlated to affective
      symptoms whereas lower central ultra slow power proportions were related to
      fatigue severity and sleep quality impairment. CONCLUSIONS: In combination with
      normal (PI) or even increased SWS durations (CFS), we found consistent evidence
      for lower proportions of slow oscillations during SWS in PI and CFS.
      SIGNIFICANCE: Observing normal or increased SWS durations but lower proportions
      of ultra slow power, our findings suggest a possible quantitative compensation of
      altered homeostatic regulation.

PMID- 25620041
TI  - Functional characterisation of a TRPM2 orthologue from the sea anemone
      Nematostella vectensis in human cells.
AB  - The human non-selective cation channel TRPM2 represents a mediator of apoptosis
      triggered by oxidative stress. The principal agonist ADP-ribose binds to the
      cytosolic domain of TRPM2, which is homologous to the human ADP-ribose
      pyrophosphatase NUDT9. To further elucidate the structure-function relationship
      of this channel, we characterised a TRPM2 orthologue from the cnidarian
      Nematostella vectensis, after its expression in a human cell line. This far
      distant relative shows only 31% total sequence similarity to hTRPM2, while its C
      terminal domain has a greater resemblance to the NUDT9 enzyme. Current through
      nvTRPM2 was induced by ADPR, with a more pronounced sensitivity and faster
      kinetics than in hTRPM2. In contrast to hTRPM2, there was no response to H2O2 and
      hardly any modulatory effect by intracellular Ca(2+). The deletion of a stretch
      of 15 residues from the NUDT9 domain of nvTRPM2, which is absent in hTRPM2, did
      not change the response to ADPR but enabled activation of the channel by H2O2 and
      increased the effects of intracellular Ca(2+). These findings shed new light on
      the evolution of TRPM2 and establish nvTRPM2 as a promising tool to decipher its
      complex gating mechanisms. 

PMID- 25620042
TI  - Hypoglycemic and hypolipidemic effects of neohesperidin derived from Citrus
      aurantium L. in diabetic KK-A(y) mice.
AB  - The present study is to investigate the possible hypoglycemic and hypolipidemic
      effects of neohesperidin (NHP) derived from Citrus aurantium L. in vivo. KK-A(y)
      mice were used as the diabetic experimental model, whereas C57BL/6 mice were used
      as normal control for a 6-week study. Treatment of NHP significantly decreased
      fasting glucose, serum glucose, and glycosylated serum protein (GSP) in KK-A(y)
      mice. It significantly elevated oral glucose tolerance and insulin sensitivity
      and decreased insulin resistance in the diabetic mice. In addition, NHP
      significantly decreased serum triglycerides (TG), total cholesterol (TCH), leptin
      level, and liver index in the KK-A(y) mice. NHP also inhibited lipid accumulation
      in the liver and decreased the size of epididymal adipocyte in the KK-A(y) mice.
      Gene expression of stearoyl-CoA desaturase 1 (SCD-1) and fatty acid synthase
      (FAS) were significantly inhibited, whereas the expression of acyl-CoA oxidase
      (ACOX) was significantly induced by NHP treatment in the liver of KK-A(y) mice.
      In addition, elevated level of phosphorylation of hepatic AMPK was observed in
      NHP-treated mice. Therefore, the activation of the AMPK pathway and regulation of
      its target genes, including SCD-1, FAS, and ACOX, may play important roles in the
      hypoglycemic and hypolipidemic effects of NHP in vivo, and NHP may have great
      potential in the prevention of diabetes and its complications. 

PMID- 25620043
TI  - Initial orthodontic tooth movement of a multirooted tooth: a 3D study of a rat
      molar.
AB  - OBJECTIVE: To elucidate the 3D interactions in the tooth-PDL-bone complex
      immediately after application of orthodontic forces and their implications on
      tooth movement and function. METHODS: A special visualization method using
      microCT allows us to directly image in 3D the movements of a multirooted molar
      tooth inside the alveolar bone as well as the collagenous network of the PDL.
      Using fresh, unstained rat mandibular 1st molar under mesial loads of 0.5-1 N, we
      address basic concepts in orthodontics during the initial stages of orthodontic
      movement. RESULTS: We show that immediately after the application of orthodontic
      load, direct distinct contacts between the tooth and the bone form in the
      furcation area. These contacts limit tooth movement and interfere with whole body
      translation. Only localized sites of highly compressed PDL between the root
      surfaces and the bone were observed. In general, the collagenous network of the
      PDL appeared loose and not densely packed in the compressed side. On the tension
      side, the fibers maintained their overall orientation without any significant
      extension of the fibers. CONCLUSIONS: Localized direct contact areas between the
      tooth roots and the bone at the furcation already form within a few minutes of
      orthodontic tooth movement. This direct and localized bone involvement guides the
      movement trajectory and provides a mechanism for the miscorrelation found between
      force levels and tooth movement during the initial stages of an orthodontic tooth
      movement.

PMID- 25620044
TI  - Optical coherence tomography versus intravascular ultrasound in the evaluation of
      observer variability and reliability in the assessment of stent deployment: the
      OCTIVUS study.
AB  - OBJECTIVES: To compare the variability in the assessment of coronary stents among
      interventional cardiologists (readers) using optical coherence tomography (OCT)
      and intravascular ultrasound (IVUS). BACKGROUND: IVUS is established and
      validated in the evaluation of coronary stent. For cardiologists without core lab
      expertise, the utility of IVUS is limited by image quality. OCT yields higher
      image resolution; however, the consistency with which these readers interpret OCT
      images has not been fully evaluated or compared with IVUS. METHODS: OCT and IVUS
      image sets (five pairs) obtained after stent placement were reviewed by readers
      with clinical experience in both modalities. Parameters assessed included stent
      expansion and symmetry, reference vessel and in-stent cross-sectional area (CSA)
      and diameter, and stent strut apposition as well as Multicenter Ultrasound
      Stenting in Coronaries criteria. These interpretations were compared with core
      lab readings and examined for interobserver variability. RESULTS: The
      interobserver variability for measurement of in-stent CSA was 1.34 mm(2) using
      IVUS compared with 0.85 mm(2) using OCT (P = 0.024). Variation in the deviation
      from core lab measurement of in-stent CSA for IVUS was 1.48 mm(2) compared with
      0.87 mm(2) for OCT (P = 0.042). The interobserver agreement for obtaining the
      Multicenter Ultrasound Stenting in Coronaries criteria using IVUS was 80.4%
      compared with 81.1% using OCT (P = 0.78). Compared with the corelab measurement,
      the readers obtained an agreement of 72.7% using IVUS vs. 67.3% using OCT (P =
      0.43). CONCLUSION: In the assessment of deployed coronary stents by practicing
      cardiologists, OCT images are interpreted more consistently compared with IVUS
      and can be used to assess stent deployment using IVUS-validated metrics.

PMID- 25620045
TI  - Iatrogenic hypoglycemia and quality of life in patients with type 2 diabetes
      mellitus.

PMID- 25620046
TI  - Single-molecule tracking and super-resolution imaging shed light on cholera toxin
      transcription activation.
AB  - Because of their small size, bacterial cells have long kept details about their
      inner workings a secret. We are starting to decipher their mechanistic secrets,
      in no small part due to the development of single-molecule and super-resolution
      fluorescence imaging, the subject of the 2014 Nobel Prize in Chemistry. These new
      methods have yielded a surge of discoveries about the subcellular organization
      and dynamics inside microbes. One example is an increased understanding of the
      virulence pathway within the cholera-causing microbe, Vibrio cholerae. Here,
      expression of the cholera toxin is regulated by an unusual step: transcription is
      activated by two inner-membrane proteins. Relating potential cooperative
      mechanisms between these two membrane-bound proteins and transcription activation
      is difficult using ensemble methods, which could obfuscate any underlying
      heterogeneity. Recent efforts using single-molecule tracking and super-resolution
      imaging have begun to unravel the heterogeneity. The results support a mechanism
      in which one membrane protein recruits the other in order to activate
      transcription. The study helps to explain the relationship between the two
      proteins in cholera replication and also sheds light on the broader process of
      membrane-bound transcription activation which, although uncommon, has been
      observed in other organisms. 

PMID- 25620047
TI  - Inappropriate ICD shocks in pediatrics and congenital heart disease patients:
      Risk factors and programming strategies.
AB  - BACKGROUND: Inappropriate implantable cardioverter-defibrillator (ICD) shocks are
      a common and significant problem in pediatric patients and patients with
      congenital heart disease (CHD). OBJECTIVE: The purpose of this study was to
      evaluate the effect of programming high detection rates and long detection
      duration on inappropriate shocks in this population. METHODS: We performed a
      retrospective review of all patients with ICDs at a single pediatric center.
      Inappropriate shocks were defined as a shock for any rhythm except ventricular
      tachycardia or fibrillation. RESULTS: A total of 144 patients were included, 63
      (44%) with CHD. At implant, mean age and weight were 17 +/- 10 years and 57 +/-
      23 kg. ICDs were single chamber in 35 (24%), dual chamber in 97 (67%), and
      biventricular in 12 (8%). The mean follow-up duration was 42 +/- 39 months.
      Appropriate shocks occurred in 29 (20.1%) and inappropriate shocks in 14 (9.7%).
      Causes of inappropriate shocks were supraventricular tachycardia (n = 6), lead
      malfunction (n = 4), sinus tachycardia (n = 3), and T-wave oversensing (n = 1).
      The mean ventricular fibrillation detection rate was 222 +/- 15 beats/min, and
      the detection duration was 18 +/- 12 beats. Patients with shocks programmed in
      the ventricular tachycardia zone were more likely to receive an inappropriate
      shock (P = .03). There were no associations between inappropriate shocks and age
      or weight at implant, presence of CHD, dual-chamber vs single-chamber device,
      history of supraventricular tachycardia, or antiarrhythmic use. There were no
      adverse events as a result of programming. CONCLUSION: Programming high detection
      rates and long detection duration resulted in a low rate of inappropriate shocks
      without associated adverse events in this large cohort of pediatric and CHD
      patients with ICDs.

PMID- 25620048
TI  - Selective activation of heteromeric SK channels contributes to action potential
      repolarization in mouse atrial myocytes.
AB  - BACKGROUND: Activation of small conductance calcium-activated potassium (SK)
      channels is proposed to contribute to repolarization of the action potential in
      atrial myocytes. This role is controversial, as these cardiac SK channels appear
      to exhibit an uncharacteristic pharmacology. OBJECTIVES: The objectives of this
      study were to resolve whether activation of SK channels contributes to atrial
      action potential repolarization and to determine the likely subunit composition
      of the channel. METHODS: The effect of 2 SK channel inhibitors was assessed on
      outward current evoked in voltage clamp and on action potential duration in
      perforated patch and whole-cell current clamp recording from acutely isolated
      mouse atrial myocytes. The presence of SK channel subunits was assessed using
      immunocytochemistry. RESULTS: A significant component of outward current was
      reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed
      a sensitivity indicating that this current was carried by homomeric SK2 channels.
      Action potential duration was significantly prolonged by UCL1684, but not by
      apamin. This effect was accompanied by an increase in beat-to-beat variability
      and action potential triangulation. This pharmacology was matched by that of
      expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry
      showed that atrial myocytes express both SK2 and SK3 channels with an overlapping
      expression pattern. CONCLUSION: Only proposed heteromeric SK2-SK3 channels are
      physiologically activated to contribute to action potential repolarization, which
      is indicated by the difference in pharmacology of evoked outward current and
      prolongation of atrial action potential duration. The effect of blocking this
      channel on the action potential suggests that SK channel inhibition during
      cardiac function has the potential to be proarrhythmic.

PMID- 25620049
TI  - Sexual dimorphism and brain lateralization impact behavioral and histological
      outcomes following hypoxia-ischemia in P3 and P7 rats.
AB  - Neonatal cerebral hypoxia-ischemia (HI) is a major cause of neurological
      disorders and the most common cause of death and permanent disability worldwide,
      affecting 1-2/1000 live term births and up to 60% of preterm births. The Levine
      Rice is the main experimental HI model; however, critical variables such as the
      age of animals, sex and hemisphere damaged still receive little attention in
      experimental design. We here investigated the influence of sex and hemisphere
      injured on the functional outcomes and tissue damage following early (hypoxia
      ischemia performed at postnatal day 3 (HIP3)) and late (hypoxia-ischemia
      performed at postnatalday 7 (HIP7)) HI injury in rats. Male and female 3- (P3) or
      7-day-old (P7) Wistar rats had their right or left common carotid artery occluded
      and exposed to 8% O2 for 1.5h. Sham animals had their carotids exposed but not
      occluded nor submitted to the hypoxic atmosphere. Behavioral impairments were
      assessed in the open field arena, in the Morris water maze and in the inhibitory
      avoidance task; volumetric extent of tissue damage was assessed using cresyl
      violet staining at adult age, after completing behavioral assessment. The overall
      results demonstrate that: (1) HI performed at the two distinct ages cause
      different behavioral impairments and histological damage in adult rats (2)
      behavioral deficits following neonatal HIP3 and HIP7 are task-specific and
      dependent on sex and hemisphere injured (3) HIP7 animals presented the expected
      motor and cognitive deficits (4) HIP3 animals displayed discrete but significant
      cognitive impairments in the left hemisphere-injured females (5) HI brain injury
      and its consequences are determined by animal's sex and the damaged hemisphere,
      markedly in HIP3-injured animals. 

PMID- 25620050
TI  - Ontogeny of the Early Triassic Cynodont Thrinaxodon liorhinus (Therapsida):
      Cranial Morphology.
AB  - The cranial morphology of 68 Thrinaxodon liorhinus specimens, ranging in size
      from 30 to 96 mm in basal skull length, is investigated using both qualitative
      and quantitative analyses. From this comprehensive survey, we determined that
      nine cranial features, including five in the temporal region, separated the
      sample into four ontogenetic stages. A bivariate analysis of 60 specimens
      indicated that the skull generally increased in size isometrically, with the
      exception of four regions. The orbit had negative allometry, a result consistent
      with other ontogenetic studies of tetrapods, whereas the length of the snout,
      palate, and temporal region showed positive allometry. The last trend had strong
      positive allometry indicating that during ontogeny the length of the sagittal
      crest increased at a much faster rate than the rest of the skull. The large
      number of changes in the temporal region of the skull of Thrinaxodon may indicate
      a greater development of the posterior fibres of the temporalis musculature from
      an early ontogenetic stage. For example, the posterior sagittal crest developed
      much earlier in ontogeny than the anterior crest that formed in adults, and bone
      was deposited dorsally creating a unified posterior sagittal crest rather than
      having a suture that spanned the entire depth of the skull roof. In combination
      with the isometric height of the zygomatic arch and the almost complete absence
      of the zygomatic arch angulation, these ontogenetic changes suggest that there
      was greater development of the temporalis relative to the masseter muscles,
      indicating a strong posterodorsal movement of the mandible in Thrinaxodon.

PMID- 25620051
TI  - Spin and field squeezing in a spin-orbit coupled Bose-Einstein condensate.
AB  - Recently, strong spin-orbit coupling with equal Rashba and Dresselhaus strength
      has been realized in neutral atomic Bose-Einstein condensates via a pair of Raman
      lasers. In this report, we investigate spin and field squeezing of the ground
      state in spin-orbit coupled Bose-Einstein condensate. By mapping the spin-orbit
      coupled BEC to the well-known quantum Dicke model, the Dicke type quantum phase
      transition is presented with the order parameters quantified by the spin
      polarization and occupation number of harmonic trap mode. This Dicke type quantum
      phase transition may be captured by the spin and field squeezing arising from the
      spin-orbit coupling. We further consider the effect of a finite detuning on the
      ground state and show the spin polarization and the quasi-momentum exhibit a step
      jump at zero detuning. Meanwhile, we also find that the presence of the detuning
      enhances the occupation number of harmonic trap mode, while it suppresses the
      spin and the field squeezing. 

PMID- 25620052
TI  - SlyD-dependent nickel delivery limits maturation of [NiFe]-hydrogenases in late
      stationary phase Escherichia coli cells.
AB  - Fermentatively growing Escherichia coli cells have three active [NiFe]
      hydrogenases (Hyd), two of which, Hyd-1 and Hyd-2, contribute to H2 oxidation
      while Hyd-3 couples formate oxidation to H2 evolution. Biosynthesis of all Hyd
      involves the insertion of a Fe(CN)2CO group and a subsequent insertion of nickel
      ions through the HypA/HybF, HypB and SlyD proteins. With high nickel
      concentrations the presence of none of these proteins is required, but under
      normal growth conditions and during late stationary growth SlyD is important for
      hydrogenase activities. The slyD mutation reduced H2 production during
      exponential phase growth by about 50%. Assaying stationary phase grown cells for
      the coupling of Hyd activity to the respiratory chain or formate-dependent H2
      evolution showed that SlyD is essential for both H2 evolution and H2 oxidation.
      Although introduction of plasmid-coded slyD resulted in an overall decrease of
      Hyd-2 polypeptides in slyD and hypA slyD mutants, processing and dye-reducing
      activity of the Hyd-2 enzyme was nevertheless restored. Similarly, introduction
      of the slyD plasmid restored only some H2 evolution in the slyD mutant while Hyd
      3 polypeptides and dye-reducing activity were fully restored. Taken together,
      these results indicate an essential role for SlyD in the generation of the fully
      cofactor-equipped hydrogenase large subunits in the stationary phase where the
      level of each Hyd enzyme is finely tuned by SlyD for optimal enzyme activity. 

PMID- 25620053
TI  - Simultaneous determination of senkyunolide I and senkyunolide H in rat plasma by
      LC-MS: application to a comparative pharmacokinetic study in normal and
      migrainous rats after oral administration of Chuanxiong Rhizoma extract.
AB  - A selective liquid chromatographic-mass spectrometric method has been developed
      and validated for simultaneous determination of senkyunolide I (SEI) and
      senkyunolide H (SEH) from Chuanxiong Rhizoma in rat plasma. Plasma samples were
      extracted by liquid-liquid extraction with ethyl acetate and separated on a
      Kromasil C18 column (250 * 4.6 mm, 5 um), with methanol-water (55:45, v/v) as
      mobile phase. The linear range was 0.05-25 ug/mL for SEI and 0.01-5.0 ug/mL for
      SEH, with lower limits of quantitation of 0.05 and 0.01 ug/mL, respectively.
      Intra- and inter-day precision were within 10.0 and 9.8%, and the accuracies
      (relative errors) were <9.6 and 5.9%, with the mean extraction recoveries 81.0
      86.6 and 80.5-85.0% for the two anayltes, respectively. The validated method was
      successfully applied to a comparative pharmacokinetic study of SEI and SEH in
      normal and migrainous rats after oral administration of Chuanxiong Rhizoma
      extract. The results indicated that there were obvious differences between normal
      and migrainous rats in the pharmacokinetic behavior after oral administration of
      Chuanxiong Rhizoma extract. The absorption of SEI and SEH were significantly
      increased in migrainous rats compared with normal rats.

PMID- 25620054
TI  - Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant
      chemicals.
AB  - Diesel exhaust particles (DEPs) are a major component of diesel emissions,
      responsible for a large portion of their toxicity. In this study, we examined the
      toxic effects of DEPs on endothelial cells and the role of DEP-induced heme
      oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were
      treated with an organic extract of DEPs from an automobile engine (A-DEP) or a
      forklift engine (F-DEP) for 1 and 4h. ROS generation, cell viability, lactate
      dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion
      molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression
      and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and
      enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to
      25MUg/ml of A-DEP and F-DEP significantly induced ROS production, cellular
      toxicity and greater levels of inflammatory and cellular adhesion molecules but
      to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and
      silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further
      decreased cell viability and increased expression of inflammatory and cell
      adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA
      3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell
      survival and decreased the expression of inflammatory genes. HO-1 expression
      protected HMECs from DEP-induced prooxidative and proinflammatory effects.
      Modulation of HO-1 expression could potentially serve as a therapeutic target in
      an attempt to inhibit the cardiovascular effects of ambient PM.

PMID- 25620056
TI  - Changes in cholesterol homeostasis and acute phase response link pulmonary
      exposure to multi-walled carbon nanotubes to risk of cardiovascular disease.
AB  - Adverse lung effects following pulmonary exposure to multi-walled carbon
      nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are
      less understood. Epidemiological studies have shown increased cardiovascular
      disease risk after pulmonary exposure to airborne particles, which has led to
      concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed
      parameters related to cardiovascular disease, including plasma acute phase
      response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a
      single intratracheal instillation of 0, 18, 54 or 162MUg/mouse of small,
      entangled (CNTSmall, 0.8+/-0.1MUm long) or large, thick MWCNTs (CNTLarge, 4+/
      0.4MUm long). Liver tissues and plasma were harvested 1, 3 and 28days post
      exposure. In addition, global hepatic gene expression, hepatic cholesterol
      content and liver histology were used to assess hepatic effects. The two MWCNTs
      induced similar systemic responses despite their different physicochemical
      properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low
      density/very low-density lipoprotein were significantly increased following
      exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary
      Saa3 levels. Analysis of global gene expression revealed perturbation of the same
      biological processes and pathways in liver, including the HMG-CoA reductase
      pathway. Both MWCNTs induced similar histological hepatic changes, with a
      tendency towards greater response following CNTLarge exposure. Overall, we show
      that pulmonary exposure to two different MWCNTs induces similar systemic and
      hepatic responses, including changes in plasma APR, lipid composition, hepatic
      gene expression and liver morphology. The results link pulmonary exposure to
      MWCNTs with risk of cardiovascular disease. 

PMID- 25620055
TI  - 24-hour human urine and serum profiles of bisphenol A: Evidence against
      sublingual absorption following ingestion in soup.
AB  - Extensive first-pass metabolism of ingested bisphenol A (BPA) in the gastro
      intestinal tract and liver restricts blood concentrations of bioactive BPA to <1%
      of total BPA in humans and non-human primates. Absorption of ingested BPA through
      non-metabolizing tissues of the oral cavity, recently demonstrated in dogs, could
      lead to the higher serum BPA concentrations reported in some human biomonitoring
      studies. We hypothesized that the extensive interaction with the oral mucosa by a
      liquid matrix, like soup, relative to solid food or capsules, might enhance
      absorption through non-metabolizing oral cavity tissues in humans, producing
      higher bioavailability and higher serum BPA concentrations. Concurrent serum and
      urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were
      measured over a 24hour period in 10 adult male volunteers following ingestion of
      30MUg d6-BPA/kg body weight in soup. Absorption of d6-BPA was rapid (t1/2=0.45h)
      and elimination of the administered dose was complete 24h post-ingestion,
      evidence against any tissue depot for BPA. The maximum serum d6-BPA concentration
      was 0.43nM at 1.6h after administration and represented <0.3% of total d6-BPA.
      Pharmacokinetic parameters, pharmacokinetic model simulations, and the
      significantly faster appearance half-life of d6-BPA-glucuronide compared to d6
      BPA (0.29h vs 0.45h) were evidence against meaningful absorption of BPA in humans
      through any non-metabolizing tissue (<1%). This study confirms that typical
      exposure to BPA in food produces picomolar to subpicomolar serum BPA
      concentrations in humans, not nM concentrations reported in some biomonitoring
      studies. 

PMID- 25620057
TI  - Molecular basis of carcinogenicity of tungsten alloy particles.
AB  - The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91-6-3) induces
      rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether
      this effect is species-specific human HSkMc primary muscle cells were exposed to
      WNC 91-6-3 particles and responses were compared with those from a rat skeletal
      muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay
      and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was
      measured and oligonucleotide microarrays were used for transcriptional profiling.
      WNC 91-6-3 particles caused toxicity in cells adjacent to the particles and also
      increased DNA strand breaks. Inhibition of caspase 3 by WNC 91-6-3 occurred in
      rat but not in human cells. In both rat and human cells, the transcriptional
      response to WNC 91-6-3 showed repression of transcripts encoding muscle-specific
      proteins with induction of glycolysis, hypoxia, stress responses and transcripts
      associated with DNA damage and cell death. In human cells, genes encoding
      metallothioneins were also induced, together with genes related to angiogenesis,
      dysregulation of apoptosis and proliferation consistent with pre-neoplastic
      changes. An alloy containing iron, WNF 97-2-1, which is non-carcinogenic in vivo
      in rats, did not show these transcriptional changes in vitro in either species
      while the corresponding cobalt-containing alloy, WNC 97-2-1 elicited similar
      responses to WNC 91-6-3. Tungsten alloys containing both nickel and cobalt
      therefore have the potential to be carcinogenic in man and in vitro assays
      coupled with transcriptomics can be used to identify alloys, which may lead to
      tumour formation, by dysregulation of biochemical processes. 

PMID- 25620059
TI  - Genistein modulates the expression of NF-kappaB and MAPK (p-38 and ERK1/2),
      thereby attenuating d-Galactosamine induced fulminant hepatic failure in Wistar
      rats.
AB  - Genistein is an isoflavanoid abundantly found in soy. It has been found to play
      an important role in the prevention of various chronic diseases including cancer.
      In this study, we evaluated potential therapeutic properties of Genistein against
      d-Galactosamine (d-GalN) induced inflammation and hepatotoxicity in male Wistar
      rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal
      injection of d-GalN (700mg/kgBW). Genistein (5mg/kgBW/day) was given as pre
      treatment for 30days via intra-gastric route followed by d-GalN (700mg/kgBW)
      injection. The hepatoprotective and curative effects of Genistein were evident
      from a significant decrease in the serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) levels as well as prevention of histological
      damage by pre-treatment of Genistein. Genistein pre-treatment significantly
      inhibited the increased protein levels of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and
      prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly
      suppressed the production of d-GalN-induced proinflammatory cytokines, including
      tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. These
      inhibitory effects were associated with the suppression of nuclear factor-kappa B
      (NF-KB) activation, IKKalpha/beta and Mitogen activated protein kinase (MAPK)
      phosphorylation by Genistein in d-GalN-treated animals. In conclusion, our
      results suggest that Genistein may serve as a potential supplement in the
      prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to
      maintain the redox potential and strengthens the antioxidant defense system of a
      cell. 

PMID- 25620060
TI  - Derivation from first principles of the statistical distribution of the mass peak
      intensities of MS data.
AB  - Despite the widespread use of mass spectrometry (MS) in a broad range of
      disciplines, the nature of MS data remains very poorly understood, and this
      places important constraints on the quality of MS data analysis as well as on the
      effectiveness of MS instrument design. In the following, a procedure for
      calculating the statistical distribution of the mass peak intensity for MS
      instruments that use analog-to-digital converters (ADCs) and electron multipliers
      is presented. It is demonstrated that the physical processes underlying the data
      generation process, from the generation of the ions to the signal induced at the
      detector, and on to the digitization of the resulting voltage pulse, result in
      data that can be well-approximated by a Gaussian distribution whose mean and
      variance are determined by physically meaningful instrumental parameters. This
      allows for a very precise understanding of the signal-to-noise ratio of mass peak
      intensities and suggests novel ways of improving it. Moreover, it is a
      prerequisite for being able to address virtually all data analytical problems in
      downstream analyses in a statistically rigorous manner. The model is validated
      with experimental data. 

PMID- 25620058
TI  - Tunicamycin-induced unfolded protein response in the developing mouse brain.
AB  - Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER)
      causes ER stress, resulting in the activation of the unfolded protein response
      (UPR). ER stress and UPR are associated with many neurodevelopmental and
      neurodegenerative disorders. The developing brain is particularly susceptible to
      environmental insults which may cause ER stress. We evaluated the UPR in the
      brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was
      administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25.
      Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice
      of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p
      eIF2alpha, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25
      mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4
      mice, tunicamycin-induced caspase-3 activation was observed in layer II of the
      parietal and optical cortex, CA1-CA3 and the subiculum of the hippocampus, the
      cerebellar external germinal layer and the superior/inferior colliculus.
      Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much
      lesser degree and mainly located in the dentate gyrus of the hippocampus, deep
      cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain
      of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons
      were sensitive to tunicamycin-induced cell death in culture, but became resistant
      as they matured in vitro. These results suggest that the UPR is developmentally
      regulated and the immature brain is more susceptible to ER stress. 

PMID- 25620061
TI  - Percutaneous ethanol injection or percutaneous acetic acid injection for early
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common global
      cancer. When HCC is diagnosed early, interventions such as percutaneous ethanol
      injection (PEI), percutaneous acetic acid injection (PAI), or radiofrequency
      (thermal) ablation (RF(T)A) may have curative potential and represent less
      invasive alternatives to surgery. OBJECTIVES: To evaluate the beneficial and
      harmful effects of PEI or PAI in adults with early HCC defined according to the
      Milan criteria, that is, one cancer nodule up to 5 cm in diameter or up to three
      cancer nodules up to 3 cm in diameter compared with no intervention, sham
      intervention, each other, other percutaneous interventions, or surgery. SEARCH
      METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register
      (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014,
      Issue 6), MEDLINE (1946 to July 2014), EMBASE (1976 to July 2014), and Science
      Citation Index Expanded (1900 to July 2014). We handsearched meeting abstracts of
      six oncological and hepatological societies and references of articles to July
      2014. We contacted researchers in the field. SELECTION CRITERIA: We considered
      randomised clinical trials comparing PEI or PAI versus no intervention, sham
      intervention, each other, other percutaneous interventions, or surgery for the
      treatment of early HCC regardless of blinding, publication status, or language.
      We excluded studies comparing RFA or combination of different interventions as
      such interventions have been or will be addressed in other Cochrane Hepato
      Biliary Group systematic reviews. DATA COLLECTION AND ANALYSIS: Two review
      authors independently selected trials for inclusion, and extracted and analysed
      data. We calculated the hazard ratios (HR) for median overall survival and
      recurrence-free survival using the Cox regression model with Parmar's method. We
      reported type and number of adverse events descriptively. We assessed risk of
      bias by The Cochrane Collaboration domains to reduce systematic errors and risk
      of play of chance by trial sequential analysis to reduce random errors. We
      assessed the methodological quality with GRADE. MAIN RESULTS: We identified three
      randomised trials with 261 participants for inclusion. The risk of bias was low
      in one and high in two trials.Two of the randomised trials compared PEI versus
      PAI; we included 185 participants in the analysis. The overall survival (HR 1.47;
      95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42;
      95% CI 0.68 to 2.94) were not statistically significantly different between the
      intervention groups of the two trials. Trial sequential analysis for the
      comparison PEI versus PAI including two trials revealed that the number of
      participants that were included in the trials were insufficient in order to judge
      a relative risk reduction of 20%. Data on the duration of hospital stay were
      available from one trial for the comparison PEI versus PAI showing a
      significantly shorter hospital stay for the participants treated with PEI (mean
      1.7 days; range 2 to 3 days) versus PAI (mean 2.2 days; range 2 to 5 days).
      Quality of life was not reported. There were only mild adverse events in
      participants treated with either PEI or PAI such as transient fever, flushing,
      and local pain.One randomised trial compared PEI versus surgery; we included 76
      participants in the analyses. There was no significant difference in the overall
      survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35;
      95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group
      while three postoperative deaths occurred in the surgery group.In addition to the
      three randomised trials, we identified one quasi-randomised study comparing PEI
      versus PAI. Due to methodological flaws of the study, we extracted only the data
      on adverse events and presented them in a narrative way.We found no randomised
      trials that compared PEI or PAI versus no intervention, best supportive care,
      sham intervention, or other percutaneous local ablative therapies excluding RFTA.
      We found also no randomised clinical trials that compared PAI versus other
      interventional treatments or surgery. We identified two ongoing randomised
      clinical trials. One of these two trials compares PEI versus surgery and the
      other PEI versus transarterial chemoembolization. To date, it is unclear whether
      the trials will be eligible for inclusion in this meta-analysis as the data are
      not yet available. This review will not be updated until new randomised clinical
      trials are published and can be used for analysis. AUTHORS' CONCLUSIONS: PEI
      versus PAI did not differ significantly regarding benefits and harms in people
      with early HCC, but the two included trials had only a limited number of
      participants and one trial was judged a high risk of bias. Thus, the current
      evidence precludes us from making any firm conclusions.There was also
      insufficient evidence to determine whether PEI versus surgery (segmental liver
      resection) was more effective, because conclusions were based on a single
      randomised trial. While some data from this single trial suggested that PEI was
      safer, the high risk of bias and the lack of any confirmatory evidence make a
      reliable assessment impossible.We found no trials assessing PEI or PAI versus no
      intervention, best supportive care, or sham intervention.There is a need for more
      randomised clinical trials assessing interventions for people with early stage
      HCC. Such trials should be conducted with low risks of systematic errors and
      random errors.

PMID- 25620062
TI  - Preparation of pediatric patients for treatment with proton beam therapy.
AB  - PURPOSE: Anesthesia is often used in proton beam therapy (PBT) for pediatric
      patients and this may prolong the treatment time. The aim of the study was to
      examine preparation of pediatric patients to allow smooth performance of PBT.
      MATERIAL AND METHODS: Preparation was initiated 1-2days before treatment planning
      CT and continued for 10days. The patient first visited the facility to become
      familiar with the treatment room and staff. As the second step, the patient
      stayed in the treatment bed for a certain time with their mother, and then stayed
      on the treatment bed alone. Special fixtures painted with characters, music, and
      gifts were also prepared. RESULTS: From 2010 to 2014, 111 pediatric patients
      underwent PBT. These patients were divided into 3 groups: 40 who could follow
      instructions well (group A, median age: 13.6years old), 60 who could communicate,
      but found it difficult to stay alone for a long time (group B, median age:
      4.6years old), and 11 who could not follow instructions (group C, median age:
      1.6years old). Preparation was used for patients in group B. The mean treatment
      times in groups A, B and C were 13.6, 17.1, and 15.6min, respectively, on PBT
      treatment days 2-6, and 11.8, 13.0, and 16.9min, respectively, for the last 5days
      of PBT treatment. The time reduction was significant in group B (p=0.003).
      CONCLUSION: Preparation is useful for pediatric patients who can communicate.
      This approach allows PBT to be conducted more smoothly over a shorter treatment
      time.

PMID- 25620063
TI  - A new method to estimate doses to the normal tissues after past extended and
      involved field radiotherapy for Hodgkin lymphoma.
AB  - INTRODUCTION: Reconstruction of radiotherapy (RT) performed decades ago is
      challenging, but is necessary to address dose-response questions from
      epidemiological data and may be relevant in re-irradiation scenarios. Here, a
      novel method to reconstruct extended and involved field RT for patients with
      Hodgkin lymphoma was used. MATERIALS AND METHODS: For 46 model patients, 29
      organs at risk (OARs) were contoured and seven treatment fields reconstructed
      (mantle, mediastinal, right/left neck, right/left axillary, and spleen field).
      Extended and involved field RT were simulated by generating RT plans by
      superpositions of the seven individual fields. The mean (standard deviation) of
      the 46 individual mean organ doses were extracted as percent of prescribed dose
      for each field superposition. RESULTS: The estimated mean doses to the OARs from
      17 field combinations were presented. The inter-patient variability was found to
      be a larger contributor to the uncertainty than the field simulation process. The
      inter-patient variability depended on the OAR and primarily affected the
      estimates for OARs located at the edge of the RT field. CONCLUSIONS: Dose
      estimates for 29 OARs were reported from extended and involved field RT. These
      estimates could be employed when individual reconstruction is not feasible and
      estimated doses from past treatments are needed.

PMID- 25620065
TI  - Nerve ultrasound in a case of multifocal motor neuropathy without conduction
      block.
AB  - INTRODUCTION: Multifocal nerve enlargements and ultrastructural changes either
      corresponding or not to sites of existing conduction blocks have been described
      in demyelinating polyneuropathies using multiple imaging techniques. METHODS:
      Using the emerging technique of peripheral nerve ultrasonography we investigated
      the peripheral nerves of a patient with multifocal motor neuropathy (MMN) without
      conduction block. RESULTS: In this case of MMN without conduction blocks we found
      multifocal nerve enlargements in the ultrasonography and electrodiagnostic signs
      of acute and chronic denervation associated with positive anti-GM1 IgM
      antibodies. CONCLUSIONS: This case shows that nerve ultrasound can be a
      complementary tool for diagnosing multifocal motor neuropathy without typical
      electrodiagnostic features.

PMID- 25620066
TI  - Lymphovascular invasion and nodal metastasis in intramucosal adenocarcinoma of
      the esophagus and esophagogastric junction.
AB  - OBJECTIVE: To evaluate the tumor parameters predictive of lymphovascular invasion
      (LVI) and nodal metastases in intramucosal adenocarcinoma (IMAC) of the esophagus
      and esophagogastric junction. METHODS: In all, 171 cases of IMAC from
      esophagectomy database (1986-2009) were reviewed. LVI was evaluated on HE and by
      immunohistochemistry stain for D2-40 (in selected cases). Univariate analysis was
      performed to identify predictors for LVI (in this cohort) and nodal metastasis
      (for pooled data from literature review). RESULTS: Altogether 150 IMAC were
      included in the study after histology review; 7 (4.7%) showed LVI and one (0.7%)
      had nodal metastasis. LVI-positive IMAC were thicker (tumor thickness 3.0 +/- 2.8
      mm vs 1.3 +/- 1.2 mm, P = 0.01), and more likely to invade the outer muscularis
      mucosae (M3) (P = 0.004), be poorly differentiated (P < 0.001), and to show a
      nodular or plaque-like lesion (P = 0.04) compared with LVI-negative IMAC.
      Patients' age, gender, the frequency of tumor multifocality, ulceration and tumor
      size were not significantly different between these two groups. The pooled rates
      of LVI and nodal metastases in IMAC from five published studies and this cohort
      were 6.0% (range 2.9-16.7%) and 3.4% (range 0-10.0%), respectively. Pooled
      analysis of studies with histology review showed that LVI in IMAC was associated
      with a nodal metastases rate of 27.3%. CONCLUSION: For IMAC of the esophagus and
      esophagogastric junction, LVI is associated with tumor thickness, M3 invasion,
      poor differentiation and the presence of nodular or plaque-like lesion; by pooled
      analysis, it is associated with a risk of nodal metastasis of 27.3%.

PMID- 25620067
TI  - Self-assembled nanoscale coordination polymers carrying oxaliplatin and
      gemcitabine for synergistic combination therapy of pancreatic cancer.
AB  - Gemcitabine has long been the standard of care for treating pancreatic ductal
      adenocarcinoma (PDAC), despite its poor pharmacokinetics/dynamics and rapid
      development of drug resistance. In this study, we have developed a novel
      nanoparticle platform based on nanoscale coordination polymer-1 (NCP-1) for
      simultaneous delivery of two chemotherapeutics, oxaliplatin and gemcitabine
      monophosphate (GMP), at 30 wt.% and 12 wt.% drug loadings, respectively. A strong
      synergistic therapeutic effect of oxaliplatin and GMP was observed in vitro
      against AsPc-1 and BxPc-3 pancreatic cancer cells. NCP-1 particles effectively
      avoid uptake by the mononuclear phagocyte system (MPS) in vivo with a long blood
      circulation half-life of 10.1 +/- 3.3h, and potently inhibit tumor growth when
      compared to NCP particles carrying oxaliplatin or GMP alone. Our findings
      demonstrate NCP-1 as a novel nanocarrier for the co-delivery of two
      chemotherapeutics that have distinctive mechanisms of action to simultaneously
      disrupt multiple anticancer pathways with maximal therapeutic efficacy and
      minimal side effects.

PMID- 25620069
TI  - Hollow fiber based liquid-liquid-liquid microextraction combined with sweeping
      micellar electrokinetic chromatography for the sensitive determination of second
      generation antidepressants in human fluids.
AB  - An effective dual preconcentration method involving off-line hollow fiber liquid
      liquid-liquid microextraction (HF-LLLME) and on-line sweeping micellar
      electrokinetic chromatography (sweeping-MEKC) was proposed for the determination
      of five second-generation antidepressants, including fluoxetine, sertraline,
      paroxetine, fluvoxamine and citalopram. In HF-LLLME, the analytes were extracted
      from the sample solution into phenetole impregnated in the pores of the hollow
      fiber and then back-extracted into 10 MUL 0.1 mol L(-1) HAc inside the hollow
      fiber. Then, the acceptor phase was spiked with 2.8 MUL isopropanol (IPA) and
      introduced into CE for sweeping. In the sweeping-MEKC process, five target
      analytes were separated in less than 15 min with a background electrolyte
      consisting of 76% (v/v) 50 mmol L(-1) citric acid (pH 2.2) containing 100 mmol L(
      1) sodium dodecyl sulfate (SDS) and 24% (v/v) IPA. The hydrodynamic injection was
      performed at 50 mbar for 140 s. Under optimized conditions, the limits of
      detection were in the range of 0.40-1.55 MUg L(-1) with enrichment factors of
      1897- to 5952-fold for target analytes, with a dynamic linear range of 0.6/5.0
      200 MUg L(-1). The developed method demonstrated excellent clean-up ability and
      high enrichment factors and was successfully applied to the analysis of target
      analytes in human urine and plasma samples. 

PMID- 25620068
TI  - Solid microparticles based on chitosan or methyl-beta-cyclodextrin: a first
      formulative approach to increase the nose-to-brain transport of deferoxamine
      mesylate.
AB  - We propose the formulation and characterization of solid microparticles as nasal
      drug delivery systems able to increase the nose-to-brain transport of
      deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain
      barrier and inducing negative peripheral impacts. Spherical chitosan chloride and
      methyl-beta-cyclodextrin microparticles loaded with DFO (DCH and MCD,
      respectively) were obtained by spray drying. Their volume-surface diameters
      ranged from 1.77 +/- 0.06 MUm (DCH) to 3.47 +/- 0.05 MUm (MCD); the aerodynamic
      diameters were about 1.1 MUm and their drug content was about 30%. In comparison
      with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes,
      similarly as shown by ex vivo permeation studies across porcine nasal mucosa.
      Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12
      cells (neuron-like), but like DCH, it did not modify the DFO permeation pattern
      across Caco-2 monolayers (epithelial-like). Nasal administration to rats of 200
      MUg DFO encapsulated in the microparticles resulted in its uptake into the
      cerebrospinal fluid (CSF) with peak values ranging from 3.83 +/- 0.68 MUg/mL
      (DCH) to 14.37 +/- 1.69 MUg/mL (MCD) 30 min after insufflation of microparticles.
      No drug CSF uptake was detected after nasal administration of a DFO water
      solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD
      nasal administration were 6% and 15%, respectively. Chitosan chloride and methyl
      beta-cyclodextrins appear therefore suitable to formulate solid microparticles
      able to promote the nose to brain uptake of DFO and to limit its systemic
      exposure.

PMID- 25620074
TI  - Health literacy in the "oral exchange": an important element of patient-provider
      communication.
AB  - OBJECTIVE: Oral communication between health care providers and patients--the
      "oral exchange"--greatly impacts patient health outcomes; however, only recently
      have health literacy inquiries been incorporated into this field. This review
      examines the intersection between oral and aural literacy and the oral exchange.
      METHODS: A systematic literature search was carried out. Papers published in
      English since 2003 that specifically examine oral/aural literacy and oral patient
      provider communication were included. RESULTS: The search yielded 999 articles,
      12 of which were included in this review. Three tools have been developed to
      measure either patient or provider oral/aural literacy. There is a discrepancy
      between patient and provider oral/aural literacy levels, and high literacy demand
      is associated with reduced patient learning. Low patient oral/aural literacy is
      associated with poor health outcomes. Two interventions have been developed to
      reduce literacy demand. CONCLUSION: This review demonstrates the critical role of
      oral and aural literacy in the oral exchange, the importance of reducing literacy
      demand, and the need for future research in this field. PRACTICE IMPLICATIONS:
      Recommendations include the use of plain language and teach-back by providers, as
      well as incorporation of awareness of oral and aural literacy into community
      programs and health care provider education and training.

PMID- 25620073
TI  - Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin
      resistance, and hepatic gluconeogenesis in mice.
AB  - SCOPE: Moringa oleifera (moringa) is tropical plant traditionally used as an
      antidiabetic food. It produces structurally unique and chemically stable moringa
      isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo.
      METHODS AND RESULTS: C57BL/6L mice fed very high fat diet (VHFD) supplemented
      with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat
      mass, had improved glucose tolerance and insulin signaling, and did not develop
      fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced
      plasma insulin, leptin, resistin, cholesterol, IL-1beta, TNFalpha, and lower
      hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at
      low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs
      and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in
      adipose tissue in vivo argued these are not likely primary targets for the anti
      obesity and anti-diabetic effects observed. CONCLUSION: Data suggest that MICs
      are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert
      their effects by inhibiting rate-limiting steps in liver gluconeogenesis
      resulting in direct or indirect increase in insulin signaling and sensitivity.
      These conclusions suggest that MC may be an effective dietary food for the
      prevention and treatment of obesity and type 2 diabetes.

PMID- 25620075
TI  - Development and usability evaluation of the mHealth Tool for Lung Cancer (mHealth
      TLC): a virtual world health game for lung cancer patients.
AB  - OBJECTIVE: To test the feasibility and usability of mHealth TLC, an interactive,
      immersive 3-dimensional iPad health game that coaches lung cancer patients toward
      assertive communication strategies during first-person virtual clinics visits.
      METHOD: We observed players and conducted semi-structured interviews. Research
      questions focused on scenario believability, the impact of technical issues,
      transparency of game goals, and potential of mHealth TLC to decrease lung cancer
      stigma (LCS) and improve patient-clinician communication. RESULTS: Eight users
      confirmed mHealth TLC to be: (1) believable, (2) clinic-appropriate, and (3)
      helpful in support of informed healthcare consumers. Concerns were expressed
      about emotionally charged content and plans to use mHealth TLC in clinic settings
      as opposed to at home. CONCLUSIONS: Although the dialog and interactions
      addressed emotionally charged issues, players were able to engage, learn, and
      benefit from role-play in a virtual world. Health games have the potential to
      improve patient-clinician communication, and mHealth TLC specifically may
      decrease LCS, and promote optimal self-management. PRACTICE IMPLICATIONS: Process
      reflection revealed the need for health games to be created by experienced game
      developers in collaboration with health care experts. To prepare for this best
      practice, research institutions and game developers interested in health games
      should proactively seek out networking and collaboration opportunities.

PMID- 25620077
TI  - Preliminary validation of handheld X-ray fluorescence spectrometry:
      distinguishing osseous and dental tissue from nonbone material of similar
      chemical composition.
AB  - One of the tasks of a forensic anthropologist is to sort human bone fragments
      from other materials, which can be difficult when dealing with highly fragmented
      and taphonomically modified material. The purpose of this research is to develop
      a method using handheld X-ray fluorescence (HHXRF) spectrometry to distinguish
      human and nonhuman bone/teeth from nonbone materials of similar chemical
      composition using multivariate statistical analyses. The sample materials were
      derived primarily from previous studies: human bone and teeth, nonhuman bone,
      nonbiological materials, nonbone biological materials, and taphonomically
      modified materials. The testing included two phases, testing both the reliability
      of the instrument and the accuracy of the technique. The results indicate that
      osseous and dental tissue can be distinguished from nonbone material of similar
      chemical composition with a high degree of accuracy (94%). While it was not
      possible to discriminate rock apatite and synthetic hydroxyapatite from
      bone/teeth, this technique successfully discriminated ivory and octocoral. 

PMID- 25620076
TI  - Egg yolks inhibit activation of NF-kappaB and expression of its target genes in
      adipocytes after partial delipidation.
AB  - How composition of egg yolk (EY) influences NF-kappaB, a key transcription
      pathway in inflammation, remains unclear. We performed partial delipidation of EY
      that removed 20-30% of cholesterol and triglycerides. The resulting polar and
      nonpolar fractions were termed EY-P and EY-NP. NF-kappaB activation in response
      to EY from different suppliers and their fractions was examined in 3T3-L1
      adipocytes using a NF-kappaB response element reporter assay and by analyzing
      expression of 248 inflammatory genes. Although EY-P and EY contained similar
      level of vitamins, carotenoids, and fatty acids, only delipidated EY-P fraction
      suppressed NF-kappaB via down-regulation of toll like receptor-2 and up
      regulation of inhibitory toll interacting protein (Tollip) and lymphocyte antigen
      96 (Ly96). Our data suggest that anti-inflammatory activity of lutein and retinol
      were blunted by nonpolar lipids in EY, likely via crosstalk between SREBP and NF
      kappaB pathways in adipocytes. Thus, moderate delipidation may improve the
      beneficial properties of regular eggs. 

PMID- 25620079
TI  - MicroRNA-mRNA interactions in colorectal cancer and their role in tumor
      progression.
AB  - MicroRNAs (miRNA/miR) play an important role in gene regulatory networks through
      targeting mRNAs. They are involved in diverse biological processes such as cell
      proliferation, differentiation, angiogenesis, and apoptosis. Due to their pivotal
      effects on multiple genes and pathways, dysregulated miRNAs have been reported to
      be associated with different diseases, including colorectal cancer (CRC). Recent
      evidence indicates that aberrant miRNA expression is tightly linked with the
      initiation and progression of CRC. To elucidate the influence of miRNA regulation
      in CRC, it is critical to identify dysregulated miRNAs, their target mRNA genes
      and their involvement in gene regulatory and signaling networks. Various
      experimental and computational studies have been conducted to decipher the
      function of miRNAs involved in CRC. Experimental studies that are used for this
      purpose can be classified into two categories: direct/individual and
      indirect/high-throughput gene expression studies. Here we review miRNA target
      identification studies related to CRC with an emphasis on experimental data based
      on Luciferase reporter assays. Recent advances in determining the function of
      miRNAs and the signaling pathways they are involved in have also been summarized.
      The review helps bioinformaticians and biologists to find extensive information
      about downstream targets of dysregulated miRNAs, and their pro-/anti-CRC effects.

PMID- 25620078
TI  - Targeting osteopontin suppresses glioblastoma stem-like cell character and
      tumorigenicity in vivo.
AB  - Osteopontin (OPN) is a secreted protein involved in most aspects of tumor
      progression and metastasis development. Elevated OPN expression has been reported
      in multiple types of cancer including glioblastoma (GBM), the highest grade and
      most aggressive brain tumor. GBMs contain a subpopulation of glioma-initiating
      cells (GICs) implicated in progression, therapeutic resistance and recurrence. We
      have previously demonstrated that OPN silencing inhibited GBM cell growth in
      vitro and in vivo. Moreover, activation of CD44 signaling upon OPN ligation has
      been recently implicated in the acquisition of a stem cell phenotype by GBM
      cells. The present study is aimed to explore OPN autocrine function using shRNA
      silencing strategy in GICs enriched from GBM cell lines and a human primary GBM
      grown in EGF and bFGF defined medium. The removal of these growth factors and
      addition of serum induced a significant loss of OPN expression in GICs. We showed
      that OPN-silenced GICs were unable to grow as spheres and this capacity was
      restored by exogenous OPN. Importantly, the expression of Sox2, Oct3/4 and Nanog,
      key stemness transcription factors, was significantly decreased in GICs upon OPN
      targeting. We identified Akt/mTOR/p70S6K as the main signaling pathway triggered
      following OPN-mediated EGFR activation in GICs. Finally, in an orthotopic
      xenograft mouse model, the tumorigenic potential of U87-MG sphere cells was
      completely abrogated upon OPN silencing. Our demonstration of endogenous OPN
      major regulatory effects on GICs stemness phenotype and tumorigenicity implies a
      greater role than anticipated for OPN in GBM pathogenesis from initiation and
      progression to probable recurrence. 

PMID- 25620080
TI  - Human leukocyte antigen-G polymorphisms influence the clinical outcome in diffuse
      large B-cell lymphoma.
AB  - The role of HLA-G is extensively studied in cancer due to its inhibition of the
      immune response. Several polymorphisms in the HLA-G gene have been reported to
      significantly affect its expression. We, therefore, investigated whether
      functionally relevant HLA-G polymorphisms, HLA-G-725C/G/T, and HLA-G 14-base
      pair, have any influence on the susceptibility to diffuse large B-cell lymphoma
      (DLBCL) and its clinical course. The polymorphisms were genotyped in 207
      previously untreated patients with DLBCL and 150 unrelated controls. A
      significant difference in genotype distribution of HLA-G polymorphic genotypes
      between the patients and controls was found. The frequencies of the HLA-G-725GG
      or the HLA-G-725GC genotype were lower, and those of the HLA-G ins/ins genotype
      were higher in the patients compared with the controls. Patients carrying the HLA
      G-725CC genotype presented a higher probability of overall survival (OS) than
      subjects with other genotype combinations of HLA-G-725C/G/T (P = 0.003). The
      homozygous HLA-G del/del had a lower probability of OS than subjects carrying the
      HLA-G deletion/insertion (del/ins) or the HLA-G ins/ins genotype (P = 0.009). Two
      HLA-G genotype-based risk groups were defined according to the genotype
      distribution. The high-risk (HR) group presented a shorter OS than low-risk (LR)
      patients (P = 0.001). In a multivariate analysis adjusted for International
      Prognostic Index (IPI) factors, both the intermediate high/high IPI-risk group (P
      < 0.0001) and the HR genotype group (P = 0.004) independently increased the risk
      of death. This is the first study indicating an important role of HLA-G
      polymorphisms for the clinical course of DLBCL. The potential influence of HLA-G
      polymorphisms on the susceptibility to DLBCL thus deserves further study.

PMID- 25620082
TI  - Adolescents with cystic fibrosis: take the door, not the window.

PMID- 25620081
TI  - COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes
      among coal workers: a case-control study.
AB  - This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A)
      and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of
      chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76
      COPD cases and 48 age-matched healthy controls from a group of coal workers were
      included. The case group consisted of 35 COPD patients whose condition was
      complicated with coal workers' pneumoconiosis (CWP) and 41 COPD patients without
      CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA
      and flow cytometry, respectively. Multiple logistic regression models were
      applied to estimate the association between Hsp levels and COPD risk. Our results
      showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher
      and plasma Hsp27 levels were significantly lower in COPD cases than in controls
      (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found
      between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds
      ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7-33.5) and lower plasma
      Hsp27 levels (OR = 4.6, 95 % CI = 2.0-10.5) were significantly associated with an
      increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27
      levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95
      % CI = 2.0-22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95
      % CI = 0.9-8.9). Additionally, there were strong joint effects of different Hsps
      on COPD risk. These results showed that higher levels of plasma Hsp70 and lower
      levels of plasma Hsp27 might be associated with an increased risk of COPD among
      coal workers. They may have the potential to serve as monitoring markers for COPD
      in coal workers. 

PMID- 25620083
TI  - Pediatric solid organ transplantation and end stage disease: a slow journey
      towards understanding neurocognitive outcomes and their ramifications for
      clinical care.

PMID- 25620085
TI  - Lymph node granulomas in immunoglobulin G4-related disease.
AB  - AIMS: Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an increasingly
      recognized fibroinflammatory condition that commonly exhibits multisystem
      involvement, with localized (e.g. inflammatory pseudotumours that can mimic
      malignancy) or diffuse (leading to organ dysfunction) patterns of tissue
      involvement. The 2012 Boston criteria have standardized the histopathological
      approach to the diagnosis of IgG4-RD and require one or more of the cardinal
      morphological features with prominence of IgG4(+) plasma cells and an IgG4(+)
      /IgG(+) plasma cell ratio of at least 40%. The relative prevalence of the
      morphological criteria varies between anatomical sites, but granulomas are rarely
      found and, indeed, their presence would usually deter a pathologist from making
      this diagnosis. The aim was to characterize two cases of IgG4-RD in which
      granulomas were present and to highlight this as an unusual feature of the
      condition. METHODS AND RESULTS: We describe two cases in which the features of
      IgG4-RD were present within lymph nodes, together with granulomas. This is a
      recognized but rare morphological pattern of IgG4-RD. CONCLUSIONS: While an
      unusual finding, the presence of granulomas should not preclude a diagnosis of
      IgG4-RD in the appropriate clinicopathological context.

PMID- 25620084
TI  - Predictors of interleukin-33 and thymic stromal lymphopoietin levels in cord
      blood.
AB  - BACKGROUND: The fetal immune system is a critical window of development. The
      epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and
      interleukin-33 (IL-33) have received attention for their role in allergic
      responses but not been studied during this critical window. The objectives were
      to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples
      and identify prenatal predictors of these biomarkers. METHODS: This study
      utilized data and banked cord blood collected in the Maternal-Infant Research on
      Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001
      pregnant women. Our analytic sample comprised the 1254 women with a singleton,
      term birth with a cord blood sample. Spearman correlation coefficients (SCC) and
      logistic regression models were used to examine associations between biomarkers
      and identify potential predictors of elevated biomarker levels. RESULTS: Thymic
      stromal lymphopoietin and IL-33 were more strongly correlated with each other
      (SCC = 0.75, p < 0.0001) than with IgE (IL-33 SCC = 0.14, TSLP SCC = 0.21).
      Maternal allergy, heavy street traffic, and elevated birth weight were
      significantly associated with jointly elevated TSLP and IL-33 levels, whereas
      maternal age and female infant sex were inversely associated with elevated IgE.
      CONCLUSIONS: In this population of Canadian women and infants, TSLP and IL-33
      were detectable in cord blood, more strongly correlated with each other than with
      IgE, and associated with maternal characteristics indicative of inflammatory
      responses. This study motivates investigation into the value of cord blood IL-33
      and TSLP levels as childhood allergy predictors and raises interesting questions
      regarding in utero coordinated regulation of these cytokines.

PMID- 25620086
TI  - Prematurity reduces the severity and need for treatment of neonatal abstinence
      syndrome.
AB  - AIM: This study determined the influence of prematurity on the manifestation and
      treatment of neonatal abstinence syndrome (NAS). METHODS: This was a medical
      record review of Australian infants exposed to opiates in 2004 and 2007. Finnegan
      scores were obtained for 215 of 361 (59%) preterm infants under 37-week gestation
      and 694 of 1178 (59%) term infants. RESULTS: The mean and standard deviation (SD)
      gestational ages were 34 (3) and 38 (3) weeks for preterm and term infants,
      respectively. Maternal daily methadone doses were similar for the preterm and
      term infants with a mean (SD) of 79 mg (39) versus 72 mg (38) (p = 0.06). Maximum
      Finnegan scores were significantly lower in preterm infants (10 versus 11, p =
      0.01), scores were positively correlated with gestation and fewer preterm infants
      were medicated for NAS (40% versus 48% p = 0.05). Maximum median daily and
      interquartile range morphine doses were lower for preterm than term infants (0.5
      mg/kg/day (0.3-0.6) versus 0.5 mg/kg/day (0.4-0.7), p = 0.02). CONCLUSION:
      Preterm infants were just as likely to be monitored for withdrawal as term
      infants, but their Finnegan scores were lower and fewer preterm infants were
      treated for NAS. Whether this indicates decreased NAS severity or physiological
      immaturity is uncertain. Other means of evaluating NAS in preterm infants are
      warranted, especially long-term outcomes.

PMID- 25620087
TI  - Recording stereoscopic 3D neurosurgery with a head-mounted 3D camera system.
AB  - Stereoscopic three-dimensional (3D) imaging can present more information to the
      viewer and further enhance the learning experience over traditional two
      dimensional (2D) video. Most 3D surgical videos are recorded from the operating
      microscope and only feature the crux, or the most important part of the surgery,
      leaving out other crucial parts of surgery including the opening, approach, and
      closing of the surgical site. In addition, many other surgeries including complex
      spine, trauma, and intensive care unit procedures are also rarely recorded. We
      describe and share our experience with a commercially available head-mounted
      stereoscopic 3D camera system to obtain stereoscopic 3D recordings of these
      seldom recorded aspects of neurosurgery. The strengths and limitations of using
      the GoPro((r)) 3D system as a head-mounted stereoscopic 3D camera system in the
      operating room are reviewed in detail. Over the past several years, we have
      recorded in stereoscopic 3D over 50 cranial and spinal surgeries and created a
      library for education purposes. We have found the head-mounted stereoscopic 3D
      camera system to be a valuable asset to supplement 3D footage from a 3D
      microscope. We expect that these comprehensive 3D surgical videos will become an
      important facet of resident education and ultimately lead to improved patient
      care. 

PMID- 25620088
TI  - Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK
      pathway in esophageal squamous cell carcinoma.
AB  - Tumor-associated macrophages (TAMs) are known to be involved in the progression
      of various human malignancies. We previously demonstrated that CD204 was a useful
      marker for TAMs contributing to the angiogenesis, progression, and prognosis of
      human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned
      media of ESCC cell lines induced CD204 expression in THP-1 human monocytic
      leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells
      stimulated with TPA (macrophage [MPhi]-like THP-1 cells) treated with and without
      conditioned medium of ESCC cell line to clarify the molecular characteristics of
      TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in
      CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC
      microenvironment, not only cancer cells but also TAMs expressed Cyr61.
      Interestingly, the expression levels of Cyr61 showed a significant positive
      correlation with the number of CD204-positive macrophages in ESCCs by
      immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration
      and induced the expression of CD204 along with the activation of the MEK/ERK
      pathway in MPhi-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor
      significantly inhibited not only the Cyr61-mediated migration but also the CD204
      expression in the MPhi-like THP-1 cells. These results suggest that Cyr61 may
      contribute to the expression of CD204 and the promotion of cell migration via the
      MEK/ERK pathway in TAMs in the ESCC microenvironment. 

PMID- 25620090
TI  - Facial dynamics and emotional expressions in facial aging treatments.
AB  - Facial expressions convey emotions that form the foundation of interpersonal
      relationships, and many of these emotions promote and regulate our social
      linkages. Hence, the facial aging symptomatological analysis and the treatment
      plan must of necessity include knowledge of the facial dynamics and the emotional
      expressions of the face. This approach aims to more closely meet patients'
      expectations of natural-looking results, by correcting age-related negative
      expressions while observing the emotional language of the face. This article will
      successively describe patients' expectations, the role of facial expressions in
      relational dynamics, the relationship between facial structures and facial
      expressions, and the way facial aging mimics negative expressions. Eventually,
      therapeutic implications for facial aging treatment will be addressed. 

PMID- 25620089
TI  - A pharmacometric pulmonary model predicting the extent and rate of distribution
      from plasma to epithelial lining fluid and alveolar cells--using rifampicin as an
      example.
AB  - PURPOSE: The purpose of the study was to develop a drug-unspecific approach to
      pharmacometric modeling for predicting the rate and extent of distribution from
      plasma to epithelial lining fluid (ELF) and alveolar cells (AC) for data
      emanating from studies involving bronchoalveolar lavage (BAL) sampling, using
      rifampicin (RIF) as an example. METHODS: Data consisting of RIF plasma
      concentrations sampled at approximately 2 and 4 h postdose and ELF and AC
      concentrations quantified from one BAL sample, taken at approximately 4 h
      postdose, in 40 adult subjects without tuberculosis was used as an example for
      model development. RESULTS: This study emphasized the usage of drug-specific
      plasma pharmacokinetics (PK) for a correct characterization of plasma to
      pulmonary distribution. As such, RIF PK was described using absorption transit
      compartments and a one compartment distribution model coupled with an enzyme turn
      over model. The ELF and AC distribution model consisted of characterization of
      the rate of distribution of drug from plasma to ELF and AC by two distribution
      rate constant, k ELF and k AC, respectively. The extent of distribution to ELF
      and AC was described by unbound ELF/plasma concentration ratio (R ELF/unbound
      plasma) and unbound AC/plasma concentration ratio (R AC/unbound-plasma) which
      typical values were predicted to be 1.28 and 5.5, respectively. CONCLUSIONS: The
      model together with a drug-specific plasma PK description provides a tool for
      handling data from both single and multiple BAL sampling designs and directly
      predicts the rate and extent of distribution from plasma to ELF and AC. The model
      can be further used to investigate design aspects of optimized BAL studies.

PMID- 25620091
TI  - Morphological Awareness and Its Role in Compensation in Adults with Dyslexia.
AB  - This study examines the role of morphological awareness (MA) in literacy
      achievement and compensation in word reading of adults with dyslexia through an
      exploration of three questions: (1) Do adult dyslexics demonstrate a deficit in
      MA, and how is this potential deficit related to phonological awareness (PA)? (2)
      Does MA contribute independently to literacy skills equally in dyslexics and
      control readers? and (3) Do MA and PA skills differ in compensated and
      noncompensated dyslexics? A group of dyslexic and normal reading university
      students matched for age, education and IQ participated in this study. Group
      analysis demonstrated an MA deficit in dyslexics; as well, MA was found to
      significantly predict a greater proportion of word reading and spelling within
      the dyslexic group compared with the controls. Compensated dyslexics were also
      found to perform significantly better on the morphological task than
      noncompensated dyslexics. Additionally, no statistical difference was observed in
      MA between the normal reading controls and the compensated group (independent of
      PA and vocabulary). Results suggest that intact and strong MA skills contribute
      to the achieved compensation of this group of adults with dyslexia. Implications
      for MA based intervention strategies for people with dyslexia are discussed.

PMID- 25620092
TI  - Loss-of-function variants of the filaggrin gene are associated with clinical
      reactivity to foods.
AB  - The aim of this study was to assess the genetic association of Filaggrin loss-of
      function (FLG LOF) genetic variants with food allergy, and to investigate the
      added value of this test in diagnosing food allergy. Clinical reactivity to foods
      was diagnosed by the gold standard, the double-blind, placebo-controlled food
      challenge. Of 155 children, 33 (21.3%) children had at least one FLG LOF variant,
      and of these, 29 (87.9%) were clinically reactive to at least one food, compared
      to 73 of 122 children (59.8%) carrying wild-type alleles. The odds ratio for
      having at least one FLG LOF variant and clinical reactivity to at least one food
      was 4.9 (CI = 1.6-14.7, P = 0.005), corresponding to a relative risk of 1.5,
      compared to carriers of wild-type alleles. Prediction of food allergy improved
      when FLG LOF variants were included in the model. Therefore, genetic markers may
      be useful as an addition to clinical assessment in the diagnosis of food allergy.

PMID- 25620094
TI  - Tubulin colchicine binding site inhibitors as vascular disrupting agents in
      clinical developments.
AB  - Tumor vasculature is an important target in cancer treatment. Two distinct
      vasculartargeting therapeutic strategies are applied to attack cancer cells
      indirectly. The antiangiogenic approach intervenes in the neovascularization
      processes and blocks the formation of new blood vessels, while th e antivascular
      approach targets the established tumor blood vessels, making vascular shutdown
      and resulting in rapid haemorrhagic necrosis and tumor cell death. A number of
      compounds with diverse structural scaffolds have been designed to target tumor
      vasculature and they are called vascular disrupting agents (VDAs). The biological
      or ligand-directed VDAs utilize antibodies, peptides or growth factors to deliver
      toxins or pro-coagulants or proapoptotic affectors to tumor-related blood
      vessels, while the small-molecule VDAs selectively target tumor blood vessels and
      have little effects on the normal endothelium. Among the small-molecule VDAs, the
      tubulin colchicine binding site inhibitors have been extensively studied and many
      of them have entered the clinical trials, including CA-4P, CA-1P, AVE8062,
      OXi4503, CKD-516, BNC105P, ABT-751, CYT- 997, ZD6126, NPI-2358, MN-029 and
      EPC2407. This review makes a summary of the small-molecule VDAs in clinical
      developments and highlights some potential VDA leads or candidates for the
      treatment of tumors. 

PMID- 25620093
TI  - Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy.
AB  - Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds
      used with success in the clinical practice of innumerous diseases. Although there
      are many advancements in cancer therapy, microtubules remain as one of the few
      macromolecular targets validated for planning active anti-cancer compounds, and
      the design of drugs that modulate microtubule dynamics in unknown sites of
      tubulin is one of the goals of the medicinal chemistry. The discussion of the
      role of new and commercially available imidazole and benzimidazole derivatives as
      tubulin modulators is scattered throughout scientific literature, and indicates
      that these compounds have a tubulin modulation mechanism different from that of
      tubulin modulators clinically available, such as paclitaxel, docetaxel,
      vincristine and vinblastine. In fact, recent literature indicates that these
      derivatives inhibit microtubule formation binding to the colchicine site, present
      good pharmacokinetic properties and are capable of overcoming multidrug
      resistance in many cell lines. The understanding of the mechanisms involved in
      the imidazoles/benzimidazoles modulation of microtubule dynamics is very
      important to develop new strategies to overcome the resistance to anti-cancer
      drugs and to discover new biomarkers and targets for cancer chemotherapy. 

PMID- 25620095
TI  - Sigma-2 receptor ligands: neurobiological effects.
AB  - Sigma-2 receptor is a widely distributed protein, which can modulate cell
      proliferation and involved in the pathogenesis of tumor. Photoaffinity labelling
      techniques testified that its molecular size is about 18 kDa. Recent studies
      indicated that sigma-2 receptor modulates the cytosolic Ca2+ concentration,
      dopaminergic transmission, and cocaine-induced addiction behavior. Some sigma-2
      receptor ligands (ditolylguanidine, afobazole, etc) display the neuroprotective
      effect. Although sigma-2 receptor hasn't been cloned, tens of sigma-2 receptor
      ligands, which demonstrate high affinity and selectivity, have been identified in
      the past decade. In this review, we mainly focus on these series of selective
      sigma-2 receptor ligands, their neuropsychological effects, and molecular probes
      for tracing sigma-2 receptors in central nervous system.

PMID- 25620096
TI  - Dipeptidyl-peptidase IV (DPP IV/CD26)-activated prodrugs: a successful strategy
      for improving water solubility and oral bioavailability.
AB  - In the search of novel enzyme-based prodrug approaches to improve pharmacological
      properties of therapeutic drugs such as solubility and bioavailability,
      dipeptidyl-peptidase IV (DPP IV, also termed as CD26) enzyme activity provides a
      previously unexplored successful prodrug strategy. This review covers key aspects
      of the enzyme useful for the design of CD26-directed prodrugs. The proof-of
      concept of this prodrug technology is provided for amine-containing agents by
      directly linking appropriate di- (or oligo)peptide moieties to a free amino group
      of a non-peptidic drug through an amide bond which is specifically hydrolized by
      DPP IV/CD26. Special emphasis is also made in discussing the design and synthesis
      of more elaborated tripartite prodrug systems, for further extension of the
      strategy to hydroxy-containing drugs. The application of this technology to
      improve water solubility and oral bioavailability of prominent examples of
      antiviral nucleosides is highlighted. 

PMID- 25620097
TI  - A promising future for peptides in ophthalmology: work effectively and smartly.
AB  - Despite progress in pharmacological modalities, treatments for ocular diseases
      are inconvenient, traumatic, costly and often end in poor final visual results.
      Peptides, considered as protein fragments, can adequately mimic protein binding
      and thus are used as therapeutic agents. Chemical modifications and
      bioengineering techniques are being frequently introduced to improve efficacy and
      stability of peptides, thereby improving their druggability. Cell-penetrating
      peptides (CPPs), peptides characterized by penetrating plasma membrane, are
      famous barrier- passers. They are good candidates for carrying drugs through
      ocular barriers. Therapeutic peptide and CPP perfectly complement each other.
      Once united, they may form an optimal formula for ocular topical administration,
      which can work both effectively and smartly. The consequent noninvasive delivery
      and economical cost would actualize prophylactic intervention, early treatment
      and long-term therapy to avoid chronic irreversible vision loss. The aim of the
      current review is a) to summarize recent therapeutic peptides, both anti
      angiogenic and anti-inflammation, evidenced by animal experiments in vivo; b) to
      discuss the discovery strategies for therapeutic peptide; c) to present current
      delivery strategies for ophthalmic therapeutic peptide; and d) to introduce CPPs
      which are capable to deliver cargos to intraocular space via ocular surface
      administration. 

PMID- 25620098
TI  - A Direct Interaction Between Mitochondrial Proteins and Amyloid-beta Peptide and
      its Significance for the Progression and Treatment of Alzheimer's Disease
AB  - The amyloid-beta peptide (Abeta) has been associated with Alzheimer's disease
      (AD) for decades. The original amyloid cascade hypothesis declared that the
      insoluble extracellular plaques were responsible for Abeta toxicity. Later, this
      hypothesis has been updated and soluble intracellular Abeta forms and their
      effects within the cell have come into focus.Mitochondrial dysfunction plays an
      important role in the pathophysiology of AD. Abeta was detected inside
      mitochondria and several mitochondrial proteins were found to interact directly
      with Abeta. Such interactionscan affecta protein's function and cause damage to
      the mitochondria and finally to the whole cell.This review summarizes the current
      knowledge of mitochondrial proteins directly interacting with Abeta and discusses
      their significance for the development of therapeutics in the treatment of AD.

PMID- 25620099
TI  - Neuroprotective mechanisms of oxygen and ethanol: a potential combination therapy
      in stroke.
AB  - Currently, stroke researchers are racing to develop neuroprotective strategies
      that shield the brain from ischemia-induced injury. To date, neuroprotective
      agents that have shown promise in animal studies have failed in clinical trials.
      Since the pathophysiology of ischemic stroke exploits numerous pathways leading
      to cellular injury, a combination of neuroprotective agents may offer
      substantially better results than a single agent alone - by intervening in
      multiple mechanisms. In this paper, we consider an approach using combination
      therapy with normobaric oxygen (NBO) and ethanol. Studies indicate that NBO
      therapy improves tissue oxygenation, thereby reducing the extent of hypoxic
      injury and decelerating the development of tissue necrosis when administered
      early after stroke onset. Studies have also demonstrated that low to moderate
      levels of ethanol not only decrease the risk of stroke, but also reduce post
      ischemic sequelae. This article reviews the history of NBO and ethanol therapies,
      their mechanisms of action, the results of key clinical trials, and the rationale
      for their use as a combination therapy in the context of stroke treatment. 

PMID- 25620101
TI  - Erythropoietin in stroke therapy: friend or foe.
AB  - Recombinant human erythropoietin (rhEPO), over the past decade, was hailed as an
      auspicious therapeutic strategy for various types of brain injuries. The
      promising results from experiments conducted in animal models of stroke led to a
      hurried clinical trial that was swiftly aborted in Phase II. The multiple
      neuroprotective modalities of rhEPO failed to translate smoothly to human adult
      ischemic brain injury and provided limited aid to neonates. In light of the
      antithetical results, several questions were raised as to why and how this
      clinical trial failed. There was bolstering evidence from the preliminary studies
      that pointed to a bright future. Therefore, the objective of this review is to
      address these questions by discussing the signaling pathways of rhEPO that are
      reported to mediate the neuroprotective effect in various animal models of brain
      injury. Major biomedical bibliographical databases (MEDLINE, ISI, PubMed, and
      Cochrane Library) were searched with the use of keywords such as erythropoietin,
      stroke, neonatal hypoxia ischemia, intracerebral hemorrhage, etc. This article
      will discuss the confounding factors that influence the efficacy of rhEPO
      treatment hence challenging its clinical translatability. Lastly, rhEPO may still
      be a promising therapeutic candidate for neonates in spite of its shortcoming in
      clinical trial if caution is taken with the dose and duration of its
      administration. 

PMID- 25620103
TI  - Catalpol: a potential therapeutic for neurodegenerative diseases.
AB  - Neurodegenerative disorders, e.g., Alzheimer's disease (AD) and Parkinson's
      disease (PD) are characterized by the progressive loss of neurons and subsequent
      cognitive decline. They are mainly found in older populations. Due to increasing
      life expectancies, the toll inflicted upon society by these disorders continues
      to become heavier and more prominent. Despite extensive research, however, the
      exact etiology of these disorders is still unknown, though the pathophysiological
      mechanisms have been attributed to oxidative, inflammatory and apoptotic injury
      in the brain. Moreover, there is currently no promising therapeutic agent against
      these neurodegenerative changes. Catalpol, an iridoid glucoside contained richly
      in the roots of the small flowering plant species Rehmannia glutinosa Libosch,
      has been shown to have antioxidation, anti-inflammation, anti-apoptosis and other
      neuroprotective properties and plays a role in neuroprotection against
      hypoxic/ischemic injury, AD and PD in both in vivo and in vitro models. It may
      therefore represent a potential therapeutical agent for the treatment of
      hypoxic/ischemic injury and neurodegenerative diseases. Based on our studies and
      those of others in the literature, here we comprehensively review the role of
      Catalpol in neuroprotection against pathological conditions, especially in
      neurodegenerative states and the potential mechanisms involved. 

PMID- 25620104
TI  - Structure and Function of Prokaryotic UDP-Glucose Pyrophosphorylase, A Drug
      Target Candidate.
AB  - UDP-glucose is an essential metabolite for a variety of processes in the cell
      physiology in all organisms. In prokaryotes, it is involved in the synthesis of
      trehalose, an osmoprotectant, in galactose utilization via the Leloir pathway and
      it plays a key role in the synthesis of the components of the bacterial envelope,
      particularly the lipopolysaccharide and the capsule, which represent necessary
      virulence factors of many bacterial pathogens. UDP-glucose is synthesized in
      bacteria by the prokaryotic UDP-glucose pyrophosphorylase (UGP, EC 2.7.7.9), an
      enzyme belonging to the family of sugar:nucleotidyl transferases. Despite the
      ubiquitous distribution of UGP activity in all domains of life, prokaryotic UGPs
      are evolutionarily unrelated to their eukaryotic counterparts. Taken together,
      these features make of bacterial UGP an attractive target candidate for the
      discovery and development of new generation antibiotics. This review summarizes
      the current knowledge on structure and function of bacterial UGPs, underlying
      their potential as drug target candidates. 

PMID- 25620105
TI  - Facile and generalized encapsulations of inorganic nanocrystals with nitrogen
      doped carbonaceous coating for multifunctionality.
AB  - A simple strategy toward versatile encapsulations of inorganic nanocrystals,
      through a green hydrothermal treatment of commercial polyurethane sponge, was
      developed. This approach enables us to realize a general method to form a surface
      adherent, N-doped coating with a controllable thickness for well-defined
      structures. These composites exhibit active properties in optical applications
      and energy storage. For example, N-doped carbon encapsulated Fe2O3 nanoboxes show
      a very high discharge capacity and outstanding cyclability, and the capacity
      still remained at 1086 mA h g(-1) at a current density of 400 mA g(-1) after 200
      cycles. Our results described here provide a simple surface coating technique to
      design various functional nanostructures. 

PMID- 25620102
TI  - Ion transporters in brain tumors.
AB  - Ion transporters are important in regulation of ionic homeostasis, cell volume,
      and cellular signal transduction under physiological conditions. They have
      recently emerged as important players in cancer progression. In this review, we
      discussed two important ion transporter proteins, sodium-potassium-chloride
      cotransporter isoform 1 (NKCC-1) and sodium-hydrogen exchanger isoform 1 (NHE-1)
      in Glioblastoma multiforme (GBM) and other malignant tumors. NKCC-1 is a Na(+)-
      dependent Cl(-) transporter that mediates the movement of Na(+), K(+), and Cl(-)
      ions across the plasma membrane and maintains cell volume and intracellular K(+)
      and Cl(-) homeostasis. NHE-1 is a ubiquitously expressed cell membrane protein
      which regulates intracellular pH (pH(i)) and extracellular pH (pH(e)) homeostasis
      and cell volume. Here, we summarized recent pre-clinical experimental studies on
      NKCC-1 and NHE-1 in GBM and other malignant tumors, such as breast cancer,
      hepatocellular carcinoma, and lung cancer cells. These studies illustrated that
      pharmacological inhibition or down-regulation of these ion transporter proteins
      reduces proliferation, increases apoptosis, and suppresses migration and invasion
      of cancer cells. These new findings reveal the potentials of these ion
      transporters as new targets for cancer diagnosis and/or treatment.

PMID- 25620106
TI  - Venous thromboembolism associated with lower limb fractures after trauma: dilemma
      and management.
AB  - BACKGROUND: Trauma patients have the highest risk of developing venous
      thromboembolism (VTE) among hospitalised patients, with a reported 13-fold
      greater risk of developing VTE over non-trauma patients. This study examines the
      incidence of VTE and associated complications in trauma patients with lower limb
      fractures or injuries. METHODS: We retrospectively analysed 6,227 trauma patients
      and classified them according to injury severity score (ISS). The minor trauma
      group (ISS <=15) contained 5,637 patients and the major trauma group (ISS >15)
      contained 590 patients. RESULTS: In the minor trauma group, VTE incidence was
      1.17 %: 0.67 % were diagnosed with deep vein thrombosis (DVT) and 0.5 % with
      pulmonary embolism (PE). The readmission rate in the following 3-month period was
      11 %, of which 2.8 % were subsequently rediagnosed with VTE. The 30-day mortality
      rate was 2.2 %. Seven patients died from PE following their initial admission and
      treatment, and another patient died from PE within three months after discharge.
      In the major trauma group, the VTE incidence was 6.8 %: 5.1 % with diagnosed with
      DVT and 1.7 % with PE. The readmission rate during the following three-month
      period was 6.6 %, of which 5 % were readmitted because of VTE and two cases were
      readmitted because of DVT. The overall 30-day mortality rate was 9.7 %, but no
      patients were formally diagnosed with a fatal case of PE. CONCLUSION: This study
      found that major trauma patients have an approximate six-fold increased risk of
      developing VTE during admission compared with minor trauma patients (relative
      risk: 5.79; 95 % confidence interval: 3.94-8.49). Our findings support the use of
      extended prophylaxis to treat minor trauma patients.

PMID- 25620107
TI  - Expression and functional characterization of human lysosomal acid lipase gene
      (LIPA) mutation responsible for cholesteryl ester storage disease (CESD)
      phenotype.
AB  - Lysosomal acid lipase (LAL) is a serine hydrolase which hydrolyzes cholesteryl
      ester and triglycerides delivered to the lysosomes into free cholesterol and free
      fatty acids. Mutations in the LAL gene (LIPA) result in accumulation of
      triglycerides and cholesterol esters in various tissues of the body, leading to
      pathological conditions such as Wolman's disease (WD) and cholesteryl ester
      storage disease (CESD). CESD patients homozygous for His295Tyr (H295Y) mutation
      have less than 5% of normal LAL activity. To shed light on the molecular basis
      for this loss-of-function phenotype, we have generated the recombinant H295Y
      enzyme and studied its biophysical and biochemical properties. No significant
      differences were observed in the expression levels or glycosylation patterns
      between the mutant and the wild type LAL. However, the H295Y mutant displayed
      only residual enzymatic activity (<5%) compared to the wild type. While wild type
      LAL is mostly a monomer at pH 5.0, the vast majority H295Y exists as a high
      molecular soluble aggregate. Besides, the H295Y mutant has a 20 degrees C lower
      melting temperature compared to the wild type. Transient expression studies in WD
      fibroblasts showed that mutation of His295 to other amino acids resulted in a
      significant loss of enzymatic activity. A homology model of LAL revealed that
      His295 is located on an alpha-helix of the cap domain and could be important for
      tethering it to its core domain. The observed loss-of-function phenotype in CESD
      patients might arise from a combination of protein destabilization and the shift
      to a non-functional soluble aggregate. 

PMID- 25620109
TI  - Preventing a Bakri balloon from sliding out during "holding the cervix": "fishing
      for the balloon shaft" technique (Matsubara).

PMID- 25620108
TI  - The structure and optical properties of the [Au18(SR)14] nanocluster.
AB  - Decreasing the core size is one of the best ways to study the evolution from
      Au(I) complexes into Au nanoclusters. Toward this goal, we successfully
      synthesized the [Au18(SC6H11)14] nanocluster using the [Au18(SG)14] (SG=L
      glutathione) nanocluster as the starting material to react with cyclohexylthiol,
      and determined the X-ray structure of the cyclohexylthiol-protected
      [Au18(C6H11S)14] nanocluster. The [Au18(SR)14] cluster has a Au9 bi-octahedral
      kernel (or inner core). This Au9 inner core is built by two octahedral Au6 cores
      sharing one triangular face. One transitional gold atom is found in the Au9 core,
      which can also be considered as part of the Au4(SR)5 staple motif. These findings
      offer new insight in terms of understanding the evolution from [Au(I)(SR)]
      complexes into Au nanoclusters.

PMID- 25620100
TI  - Neonatal brain hemorrhage (NBH) of prematurity: translational mechanisms of the
      vascular-neural network.
AB  - Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of
      preterm birth. Complications result in shunt dependence and long-term structural
      changes such as posthemorrhagic hydrocephalus, periventricular leukomalacia,
      gliosis, and neurological dysfunction. Several animal models are available to
      study this condition, and many basic mechanisms, etiological factors, and outcome
      consequences, are becoming understood. NBH is an important clinical condition, of
      which treatment may potentially circumvent shunt complication, and improve
      functional recovery (cerebral palsy, and cognitive impairments). This review
      highlights key pathophysiological findings of the neonatal vascular-neural
      network in the context of molecular mechanisms targeting the posthemorrhagic
      hydrocephalus affecting this vulnerable infant population. 

PMID- 25620110
TI  - Incidence and clinical predictors of endobronchial tuberculosis in patients with
      pulmonary tuberculosis.
AB  - BACKGROUND AND OBJECTIVE: Incidence and predictors of endobronchial tuberculosis
      (EBTB) remain unknown because of the lack of prospective studies. Our objective
      was to assess the incidence and predictors of concomitant EBTB in patients with
      active pulmonary tuberculosis (PTB). METHODS: We prospectively performed routine
      bronchoscopic examination in all patients with PTB to detect EBTB. Clinical and
      bronchoscopic findings were analyzed to elucidate predictors of EBTB. RESULTS:
      Bronchoscopies of 429 PTB patients were performed at a tertiary referral hospital
      in Korea. Among those, 233 patients (54.3%) had EBTB. Female gender (odds ratio
      (OR) 4.35, 95% confidence interval (CI) 1.78-10.63), longer symptom duration (>4
      weeks; OR 1.86, 95% CI 1.05-5.46), and no previous history of tuberculosis (OR
      4.16, 95% CI 1.22-14.18) were found to be the independent predictors of
      concomitant EBTB in patients with active PTB. Most of the EBTB/PTB patients had
      mild stenosis, and more than 20% of them had severe stenosis at the time of
      diagnosis. Patients with EBTB had follow-up bronchoscopy to evaluate persistent
      airway stenosis. Persistent bronchostenosis with the lumen narrowed by more than
      one third occurred in 20.7% (30/145) of patients. The involvement length and
      decreased forced expiratory volume in 1 s were the risk factors for persistent
      bronchostenosis. CONCLUSIONS: In patients with active PTB, 50% or more have EBTB.
      Female gender and longer duration of symptoms are the main predictors of
      concomitant EBTB. Immediate diagnostic bronchoscopy in patients with active PTB
      should be considered in selected patients for detection of brocnhostenosis.

PMID- 25620111
TI  - Highly fluorinated tris(indazolyl)borate silylamido complexes of the heavier
      alkaline earth metals: synthesis, characterization, and efficient catalytic
      intramolecular hydroamination.
AB  - Heteroleptic silylamido complexes of the heavier alkaline earth elements calcium
      and strontium containing the highly fluorinated 3-phenyl
      hydrotris(indazolyl)borate {F12-Tp(4Bo, 3Ph)}(-) ligand have been synthesized by
      using salt metathesis reactions. The homoleptic precursors [Ae{N(SiMe3)2}2] (Ae =
      Ca, Sr) were treated with [Tl(F12-Tp(4Bo, 3Ph))] in pentane to form the
      corresponding heteroleptic complexes [(F12-Tp(4Bo, 3Ph))Ae{N(SiMe3)2}] (Ae = Ca
      (1); Sr (3)). Compounds 1 and 3 are inert towards intermolecular redistribution.
      The molecular structures of 1 and 3 have been determined by using X-ray
      diffraction. Compound 3 exhibits a Sr???MeSi agostic distortion. The synthesis of
      the homoleptic THF-free compound [Ca{N(SiMe2H)2}2] (4) by transamination reaction
      between [Ca{N(SiMe3)2}2] and HN(SiMe2H)2 is also reported. This precursor
      constitutes a convenient starting material for the subsequent preparation of the
      THF-free complex [(F12-Tp(4Bo, 3Ph))Ca{N(SiMe2H)2}] (5). Compound 5 is stabilized
      in the solid state by a Ca???beta-Si-H agostic interaction. Complexes 1 and 3
      have been used as precatalysts for the intramolecular hydroamination of 2,2
      dimethylpent-4-en-1-amine. Compound 1 is highly active, converting completely 200
      equivalents of aminoalkene in 16 min with 0.50 mol % catalyst loading at 25 
      degrees C.

PMID- 25620112
TI  - Developing genome-wide microsatellite markers of bamboo and their applications on
      molecular marker assisted taxonomy for accessions in the genus Phyllostachys.
AB  - Morphology-based taxonomy via exiguously reproductive organ has severely
      limitation on bamboo taxonomy, mainly owing to infrequent and unpredictable
      flowering events of bamboo. Here, we present the first genome-wide analysis and
      application of microsatellites based on the genome of moso bamboo (Phyllostachys
      edulis) to assist bamboo taxonomy. Of identified 127,593 microsatellite repeat
      motifs, the primers of 1,451 microsatellites were designed and 1,098 markers were
      physically mapped on the genome of moso bamboo. A total of 917 markers were
      successfully validated in 9 accessions with ~39.8% polymorphic potential.
      Retrieved from validated microsatellite markers, 23 markers were selected for
      polymorphic analysis among 78 accessions and 64 alleles were detected with an
      average of 2.78 alleles per primers. The cluster result indicated the majority of
      the accessions were consistent with their current taxonomic classification,
      confirming the suitability and effectiveness of the developed microsatellite
      markers. The variations of microsatellite marker in different species were
      confirmed by sequencing and in silico comparative genome mapping were
      investigated. Lastly, a bamboo microsatellites database
      (http://www.bamboogdb.org/ssr) was implemented to browse and search large
      information of bamboo microsatellites. Consequently, our results of
      microsatellite marker development are valuable for assisting bamboo taxonomy and
      investigating genomic studies in bamboo and related grass species. 

PMID- 25620113
TI  - Fetus absorbed dose evaluation in head and neck radiotherapy procedures of
      pregnant patients.
AB  - In this work the head and neck cancer treatment of a pregnant patient was
      experimentally simulated. A female anthropomorphic Alderson phantom was used and
      the absorbed dose to the fetus was evaluated protecting the patient's abdomen
      with a 7cm lead layer and using no abdomen shielding. The target volume dose was
      50Gy. The fetus doses evaluated with and without the lead shielding were,
      respectively, 0.52+/-0.039 and 0.88+/-0.052cGy. 

PMID- 25620114
TI  - Assessment of protocols in cone-beam CT with symmetric and asymmetric beams
      usingeffective dose and air kerma-area product.
AB  - This study aims to evaluate and compare protocols with similar purposes in a cone
      beam CT scanner using thermoluminescent dosimeter (TLD) and the air kerma-area
      product (PKA) as the kerma index. The measurements were performed on two
      protocols used to obtain an image of the maxilla-mandible using the equipment
      GENDEX GXCB 500: Protocol [GX1] extended diameter and asymmetric beam (14cm*8.5cm
      maxilla/mandible) and protocol [GX2] symmetrical beam (8.5cm*8.5cm
      maxillary/mandible). LiF dosimeters inserted into a female anthropomorphic
      phantom were used. For both protocols, the value of PKA was evaluated using a PTW
      Diamentor E2 meter and the multimeter Radcal Rapidose system. The results
      obtained for the effective dose/PKA were separated by protocol image. [GX1]:
      44.5uSv/478mGycm(2); [GX2]: 54.8uSv/507mGycm(2). Although the ratio of the
      diameters (14cm/8.5cm)=1.65, the ratio of effective dose values
      (44.5uSv/54.8uSv)=0.81, that is, the effective dose of the protocol with extended
      diameter is 19% smaller. The PKA values reveal very similar results between the
      two protocols. For the cases where the scanner uses an asymmetric beam to obtain
      images with large diameters that cover the entire face, there are advantages from
      the point of view of reducing the exposure of patients when compared to the use
      of symmetrical beam and/or to FOV images with a smaller diameter. 

PMID- 25620115
TI  - Altered subcellular distribution of the 75-kDa DISC1 isoform, cAMP accumulation,
      and decreased neuronal migration in schizophrenia and bipolar disorder:
      implications for neurodevelopment.
AB  - BACKGROUND: DISC1 (Disrupted-In-Schizophrenia-1) is considered a genetic risk
      factor for schizophrenia (SZ) and bipolar disorder (BD). DISC1 regulates
      microtubule stability, migration, and cAMP signaling in mammalian cell lines and
      mouse brain tissue. cAMP is a regulator of microtubule organization and migration
      in neurons. Aberrant microtubule organization has been observed in olfactory
      neuronal precursors (ONP) derived from patients with SZ and BD, which suggests
      involvement of DISC1 and cAMP. However, the biology of DISC1 in the
      physiopathology of psychiatric conditions remains elusive. AIMS: Herein,
      utilizing ONP obtained from SZ, BD patients and healthy subjects, we have studied
      DISC1 expression, protein levels, and subcellular distribution by qRT-PCR,
      immunoblotting, subcellular fractionation, and confocal microscopy. Cell
      migration and cAMP accumulation were assessed by Transwell and PKA competition
      assays. RESULTS: We found increased levels of the 75-kDa DISC1 isoform in total
      cell extracts of ONP from patients with SZ and BD compared with controls.
      Subcellular distribution showed a significant decrease of cytoplasmic DISC1
      concomitant with its augmented levels in transcription sites. Moreover,
      significant cAMP accumulation and diminished migration were also observed in
      patients' cells. CONCLUSION: Alterations of DISC1 levels and its cellular
      distribution, which negatively modify cAMP homeostasis, microtubule organization,
      and cell migration, in ONP from patients with SZ and BD, suggest that their
      presence in early stages of brain development may impact brain maturation and
      function.

PMID- 25620116
TI  - Systematic solution to homo-oligomeric structures determined by NMR.
AB  - Protein structure determination by NMR has predominantly relied on simulated
      annealing-based conformational search for a converged fold using primarily
      distance constraints, including constraints derived from nuclear Overhauser
      effects, paramagnetic relaxation enhancement, and cysteine crosslinkings.
      Although there is no guarantee that the converged fold represents the global
      minimum of the conformational space, it is generally accepted that good
      convergence is synonymous to the global minimum. Here, we show such a criterion
      breaks down in the presence of large numbers of ambiguous constraints from NMR
      experiments on homo-oligomeric protein complexes. A systematic evaluation of the
      conformational solutions that satisfy the NMR constraints of a trimeric membrane
      protein, DAGK, reveals 9 distinct folds, including the reported NMR and crystal
      structures. This result highlights the fundamental limitation of global fold
      determination for homo-oligomeric proteins using ambiguous distance constraints
      and provides a systematic solution for exhaustive enumeration of all satisfying
      solutions.

PMID- 25620117
TI  - Obesity in China: its characteristics, diagnostic criteria, and implications.

PMID- 25620118
TI  - Analysis of risk factors for schizophrenia with two different case definitions: a
      nationwide register-based external validation study.
AB  - Different case definitions of schizophrenia have been used in register based
      research. However, no previous study has externally validated two different case
      definitions of schizophrenia against a wide range of risk factors for
      schizophrenia. We investigated hazard ratios (HRs) for a wide range of risk
      factors for ICD-10 DCR schizophrenia using a nationwide Danish sample of
      2,772,144 residents born in 1955-1997. We compared one contact only (OCO) (the
      case definition of schizophrenia used in Danish register based studies) with two
      or more contacts (TMC) (a case definition of at least 2 inpatient contacts with
      schizophrenia). During the follow-up, the OCO definition included 15,074 and the
      TMC 7562 cases; i.e. half as many. The TMC case definition appeared to select for
      a worse illness course. A wide range of risk factors were uniformly associated
      with both case definitions and only slightly higher risk estimates were found for
      the TMC definition. Choosing at least 2 inpatient contacts with schizophrenia
      (TMC) instead of the currently used case definition would result in almost
      similar risk estimates for many well-established risk factors. However, this
      would also introduce selection and include considerably fewer cases and reduce
      power of e.g. genetic studies based on register-diagnosed cases only. 

PMID- 25620119
TI  - The development of insight and its relationship with suicidality over one year
      follow-up in patients with first episode psychosis.
AB  - OBJECTIVE: Insight into psychosis has been linked to suicidality, although
      inconsistently. The co-variation between insight and suicidality over time is
      under-investigated. The aim of the present study was to investigate predictors of
      suicidality in patients with first episode of psychosis (FEP) over one year,
      focusing on the relationship between insight and suicidality. METHODS: Patients
      with FEP (n=146) were interviewed as soon as possible after treatment starts and
      at one year follow-up. RESULTS: At baseline 37% of patients were suicidal,
      significantly reduced to 20% at follow-up. The effect of insight on suicidality
      was in different directions at different time-points, with insight at baseline
      increasing and insight at follow-up decreasing the risk of suicidality at follow
      up. Patients with stable levels of insight across baseline and follow-up did not
      differ in risk for suicidality at follow-up. However, patients who lost insight
      from baseline to follow-up were more often suicidal at follow-up, whilst patients
      who gained insight were more seldom suicidal at follow-up. Other predictors of
      suicidality at follow-up were more depressive episodes before study entry, longer
      duration of untreated psychosis, more suicide attempts six months prior to follow
      up, and depression at follow-up. CONCLUSION: The results indicate that the effect
      of insight on suicidality in FEP-patients depends on time of assessment and of
      changes in insight. Gaining insight during treatment was associated with reduced
      risk for suicidality, whilst losing insight had the opposite effect, underlining
      the need to monitor insight over time and tailor interventions according to
      illness phase.

PMID- 25620120
TI  - Abnormal white matter integrity in antipsychotic-naive first-episode psychosis
      patients assessed by a DTI principal component analysis.
AB  - INTRODUCTION: Diffusion tensor imaging (DTI) studies in patients with
      schizophrenia have shown abnormalities in the microstructure of white matter
      tracts. Specifically, reduced fractional anisotropy (FA) has been described
      across multiple white matter tracts, in studies that have mainly included
      patients treated with antipsychotic medications. OBJECTIVE: To compare FA in
      antipsychotic-naive patients experiencing a first episode of psychosis (FEP) to
      FA in healthy controls to demonstrate that the variance of FA can be grouped, in
      a coincidental manner, in four predetermined factors in accordance with a
      theoretical partition of the white matter tracts, using a principal components
      analysis (PCA). METHODS: Thirty-five antipsychotic-naive FEP patients and 35 age-
      and gender-matched healthy controls underwent DTI at 3T. Analysis was performed
      using a tract-based spatial statistics (TBSS) method and exploratory PCA.
      RESULTS: DTI analysis showed extensive FA reduction in white matter tracts in FEP
      patients compared with the control group. The PCA grouped the white matter tracts
      into four factors explaining 66% of the total variance. Comparison of the FA
      values within each factor highlighted the differences between FEP patients and
      controls. DISCUSSION: Our study confirms extensive white matter tracts anomalies
      in patients with schizophrenia, more specifically, in drug-naive FEP patients.
      The results also indicate that a small number of white matter tracts share common
      FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a
      growing body of literature emphasizing the need for treatments targeting white
      matter function and structure in FEP patients.

PMID- 25620122
TI  - Much ado about much: stress, dynamic biomarkers and HPA axis dysregulation along
      the trajectory to psychosis.
AB  - OBJECTIVES: In the context of a stress-vulnerability framework, hyperactivation
      of the hypothalamic-pituitary-adrenal (HPA) axis is thought contribute to the
      risk, onset and course of psychotic illness. However, recent reports regarding
      static and dynamic features of the HPA axis suggest a more complex set of
      phenomena at play in the early phases of psychosis. METHODS: We review literature
      regarding structural and functional aspects of the HPA axis in subjects at risk
      for or experiencing the first episode of psychosis, including evidence favoring
      as well as that which contradicts a model of HPA axis hyperactivation. RESULTS:
      Static measures of diurnal cortisol and hippocampal/pituitary volumes suggest
      that the HPA axis is in a hyperactivated state in early phases of psychosis. In
      contrast, the dynamic cortisol response to encountered or anticipated stress is
      blunted in the same populations. These incongruent findings need to be better
      understood. CONCLUSIONS: We consider potential explanations for the seemingly
      contradictory elevation and blunting of HPA biomarkers in the early course of
      psychosis. Finally, we propose and explore implications of a conceptual model of
      tonic HPA hyperactivation and phasic HPA blunting that integrates and reconciles
      these data.

PMID- 25620121
TI  - Endogenous oxytocin levels are associated with the perception of emotion in
      dynamic body expressions in schizophrenia.
AB  - Lower endogenous oxytocin levels have been associated with impaired social
      cognition in schizophrenia, particularly facial affect identification. Little is
      known about the relationship between oxytocin and other forms of emotion
      perception. In the current study, 41 individuals with schizophrenia (SZ) and 22
      demographically matched healthy controls (CN) completed a forced-choice affective
      body expression classification task. Stimuli included dynamic videos of male and
      female actors portraying 4 discrete emotions: happiness, sadness, anger, and
      neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results
      indicated that SZ had significantly higher plasma oxytocin concentrations than
      CN. SZ were also less accurate at identifying expressions of happiness and
      sadness; however, there were no group differences for anger or neutral stimuli. A
      group*sex interaction was also present, such that female CN were more accurate
      than male CN, whereas male SZ were more accurate than female SZ. Higher
      endogenous oxytocin levels were associated with better total recognition in both
      SZ and CN; this association was specific to females in SZ. Findings indicate that
      sex plays an important role in identifying emotional expressions in body gestures
      in SZ, and that individual differences in endogenous oxytocin predict emotion
      perception accuracy. 

PMID- 25620124
TI  - Mechanistic studies of magnetically recyclable Pd - Fe3O4 heterodimeric
      nanocrystal-catalyzed organic reactions.
AB  - Recently, we have reported several catalytic applications of new Pd - Fe3 O4
      heterodimeric nanocrystals as magnetically separable catalysts. Successful
      applications of the nanocrystals towards various useful organic reactions such as
      Suzuki, Heck, and Sonogashira coupling reactions, direct C - H arylation, and
      Wacker oxidation have been recorded. However, detailed mechanistic courses of the
      reactions have not been delineated, and it was not clear whether these processes
      proceeded through a homogeneous or heterogeneous mechanism. Here, we report
      detailed mechanistic investigations of the reactions employing the Pd - Fe3 O4
      nanoparticle catalysts. Suzuki coupling and Wacker oxidation reactions were
      chosen as two representative heterogeneous reactions employing the Pd - Fe3 O4
      catalysts, and general kinetic studies, hot filtration tests, and three-phase
      tests were carried out for the two reactions. The studies showed that the
      reactions most probably proceed via a solution-phase mechanism.

PMID- 25620123
TI  - Brief exposure to copper activates lysosomal exocytosis.
AB  - Copper (Cu) is essential mineral, but its toxicity necessitates existence of
      powerful machinery responsible for the extraction of excess Cu from the cell. Cu
      exposure was recently shown to induce the translocation of Cu pump ATP7B to the
      lysosomes followed by lysosomal exocytosis. Here we sought to investigate the
      mechanisms underlying the effect of Cu on lysosomal exocytosis. We found that
      brief exposure to Cu activates lysosomal exocytosis, which was measured as a
      release of the lysosomal digestive enzyme beta-hexosaminidase (beta-hex) into the
      extracellular medium and by the presence lysosomal protein LAMP1 at the plasma
      membrane. Such release depends on calcium (Ca) and on the lysosomal SNARE VAMP7.
      ATP7B knockdown using RNAi suppressed the basal lysosomal exocytosis, but did not
      affect the ability of Cu to activate it. ATP7B knockdown was associated with
      sustained oxidative stress. The removal of Ca from the extracellular medium
      suppressed the Cu-dependent component of the lysosomal exocytosis. We propose
      that Cu promotes lysosomal exocytosis by facilitating a Ca-dependent step of the
      lysosomal exocytosis. 

PMID- 25620125
TI  - Neurophysiological correlates of emotional directed-forgetting in persons with
      Schizophrenia: An event-related brain potential study.
AB  - BACKGROUND: Recent research has shown that patients with schizophrenia (SCZ)
      exhibit reduced directed forgetting (DF) for negative words, suggesting impaired
      ability to instantiate goal-directed inhibition in order to suppress a competing,
      emotion-driven responses (i.e., emotional memory enhancement). However, disrupted
      inhibition is not the only possible mechanism by which patients could manifest
      reduced emotional DF. Therefore, the primary objective of the current study was
      to use event-related brain potential (ERP) recordings to investigate alternative
      hypotheses. METHODS: ERPs were recorded while patients and controls completed an
      item-method DF paradigm using negative and neutral words. The N2 indexed goal
      directed inhibition of to-be-forgotten items. The late positive potential (LPP)
      indexed emotional memory enhancement for negative study items. The P300 indexed
      selective rehearsal of to-be-remembered items. RESULTS: The SCZ group exhibited a
      reduced DF effect overall, but this was not modulated by emotion. N2 amplitude at
      anterior sites was larger for forget versus remember cues in the control group
      only, but this effect was not modulated by emotion. LPP amplitude was greater for
      negative versus neutral words in both groups, independent of region. P300
      amplitude at posterior sites was greater for remember versus forget cues in the
      control group only. DISCUSSION: These data suggest that reduced DF in SCZ may be
      due, in part, to both diminished goal-directed inhibition of to-be-forgotten
      items and reduced selective rehearsal of to-be-remembered items. However, these
      data do not support the hypothesis that goal-directed, inhibitory processes are
      disrupted by competing, emotion-driven processes in SCZ. Patients' ERP data also
      suggested that they did not exhibit disproportionately heightened encoding of
      emotional stimuli, nor did they have deficient selective rehearsal of to-be
      remembered emotional items.

PMID- 25620126
TI  - Auditory brainstem's sensitivity to human voices.
AB  - Differentiating between voices is a basic social skill humans acquire early in
      life. The current study aimed to understand the subcortical mechanisms of voice
      processing by focusing on the two most important acoustical voice features: the
      fundamental frequency (F0) and harmonics. We measured frequency following
      responses in a group of young adults to a naturally produced speech syllable
      under two linguistic contexts: same-syllable and multiple-syllable. Compared to
      the same-syllable context, the multiple-syllable context contained more speech
      cues to aid voice processing. We analyzed the magnitude of the response to the F0
      and harmonics between same-talker and multiple-talker conditions within each
      linguistic context. Results establish that the human auditory brainstem is
      sensitive to different talkers as shown by enhanced harmonic responses under the
      multiple-talker compared to the same-talker condition, when the stimulus stream
      contained multiple syllables. This study thus provides the first
      electrophysiological evidence of the auditory brainstem's sensitivity to human
      voices. 

PMID- 25620127
TI  - [Vaccination against hepatitis B. Impact of vaccination programmes after 20 years
      of use in Spain. Is it time for a change?].
AB  - The highest incidence rate of hepatitis B (HB) in Spain is detected in adults
      between 20 and 54 years old, whereas the incidence in children under 1 year old
      is almost nil. The low prevalence of HB in children under 1 year is mainly due to
      the success of gestational screening strategies for the detection of HBsAg(+) in
      pregnant women, and vaccination campaigns during childhood. Currently, in Spain,
      the last dose of the HB included in the national childhood immunization program
      is administered at 6 months of age, although some studies show that delaying the
      age of the administration of the last dose of HB vaccine and increasing the time
      between doses, may improve immune memory by offering greater protection against
      this virus in the adulthood. In this article, the impact of HB vaccination in
      Spain is reviewed, and other potential vaccination strategies in our environment
      are discussed, such as extending the interval between doses, and administering
      the last dose in the second year of life, adapting the valid strategy in Spain to
      the current epidemiological context in order to reduce the prevalence of HB in
      adulthood.

PMID- 25620128
TI  - 5-HT2B Receptor Antagonists Reduce Nerve Injury-Induced Tactile Allodynia and
      Expression of 5-HT2B Receptors.
AB  - Preclinical Research This work was performed to assess the effects of intrathecal
      serotonin 2B (5-HT2B ) receptor antagonists in rats with neuropathic pain. With
      RS-127445, its effect was also determined on 5-HT2B receptor expression.
      Neuropathic pain was induced by L5/L6 spinal nerve ligation. Western blotting was
      used to determine 5-HT2B receptor expression. Dose-response curves with the 5
      HT2B receptor antagonists 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyridine (RS
      127445, 1-100 nmol) and 1-[(2-chloro-3,4-dimethoxyphenyl)methyl]-2,3,4,9
      tetrahydro-6-methyl-1H-pyrido[3,4-b]indole hydrochloride (LY-266097, 1-100 nmol)
      were performed in rats. Tactile allodynia of the left hind paw (ipsilateral) was
      assessed for 8 h after compound administration. Intrathecal injection of the 5
      HT2B receptor antagonists RS-127445 and LY-266097 diminished spinal nerve
      ligation-induced allodynia. In contrast, intrathecal injection of the 5-HT2
      receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 10
      nmol) did not modify tactile allodynia induced by nerve ligation. L5/L6 nerve
      ligation increased expression of the 5-HT2B receptors in the ipsilateral, but not
      contralateral, dorsal root ganglia. Furthermore, nerve injury also enhanced 5
      HT2B receptor expression in the ipsilateral dorsal part of the spinal cord.
      Intrathecal treatment with RS-127445 (100 nmol) diminished spinal nerve injury
      induced increased expression of 5-HT2B receptors in dorsal root ganglia and
      spinal cord. Our results imply that spinal 5-HT2B receptors are present on sites
      related to nociception and participate in neuropathic pain. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 25620129
TI  - Differential contribution of Galphai/o subunits in the response to food
      deprivation.
AB  - Behavioral responses to food deprivation are a fundamental aspect of nervous
      system function in all animals. Several signaling molecules in the mammalian
      brain act through G proteins of the Gi/o family to mediate response to food
      restriction. The present study examined whether food intake changes under a
      condition of little stimulation to eat, such as that elicited by 4h of food
      deprivation, was altered by Gi/o isoform silencing induced by
      intracerebroventricular (i.c.v.) administration of antisense
      oligodeoxynucleotides (aODN) against the alpha subunit of Gi1, Gi2, Gi3, Go1 and
      Go2. The effect of aODN pretreatments on food intake was evaluated 15, 30, 45,
      and 60min after food re-administration. Selective effects were noted on food
      intake with anti-Gialpha1 (3.12-25nmol), Gialpha3 (1.56-12.5nmol) and Goalpha2
      (3.12-25nmol) aODN exerting increase in food consumption, while anti-Gialpha2
      (3.12-25nmol) and Goalpha1 (3.12-25nmol) aODN exerting decrease in food
      consumption. We observed the effect of the alpha-subunit silencing on food
      consumption as soon as 15min after food readministration, that was still
      significant after 60min. At the highest effective doses, different for each anti
      Galphai/o subunit, any treatment did not impair motor coordination, nor modified
      spontaneous mobility and exploratory activity. These results indicate a relevant
      distinction between Galphai/o subunits on feeding behavior, and suggest that Gi/o
      proteins are critical for the integrative modulation of normal feeding behavior.
      Changes in Gi/o protein activity may be associated with modifications of feeding.

PMID- 25620130
TI  - Acanthoic acid ameliorates lipopolysaccharide-induced acute lung injury.
AB  - Acanthoic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, has
      been reported to have anti-inflammatory activities. However, the effects of
      acanthoic acid on LPS-induced acute lung injury have not been reported. The
      purpose of this study was to investigate the protective effect of acanthoic acid
      on LPS-induced ALI and to clarify the possible anti-inflammatory mechanisms. In
      vivo, an LPS-induced ALI model in mice was used to assess the protective effects
      of acanthoic acid on ALI. Meanwhile, mouse alveolar macrophages MH-S were
      stimulated with LPS in the presence or absence of acanthoic acid. The expressions
      of TNF-alpha, IL-6 and IL-1beta were measured by ELISA. LXRalpha and NF-kappaB
      expression were detected by Western blot analysis. The results showed that
      acanthoic acid downregulated LPS-induced TNF-alpha, IL-6 and IL-1beta production
      in BALF. MPO activity and lung wet-to-dry ratio were also inhibited by acanthoic
      acid. In addition, acanthoic acid attenuated lung histopathologic changes. In
      vitro, acanthoic acid inhibited inflammatory cytokines TNF-alpha, IL-6 and IL
      1beta production and NF-kappaB activation in LPS-stimulated alveolar macrophages.
      Acanthoic acid was found to up-regulated the expression of LXRalpha. The
      inhibition of acanthoic acid on LPS-induced cytokines and NF-kappaB activation
      can be abolished by LXRalpha siRNA. In conclusion, our results suggested that the
      protective effect of acanthoic acid on LPS-induced ALI was due to its ability to
      activate LXRalpha, thereby inhibiting LPS-induced inflammatory response. 

PMID- 25620131
TI  - Auraptene has the inhibitory property on murine T lymphocyte activation.
AB  - Auraptene, a citrus fruit-derived coumarin, has been reported to exert valuable
      pharmacological properties as anti-tumor, anti-inflammatory, and anti-oxidant
      agent. However, little is known about auraptene on immune responses. In this
      study, we conducted an investigation to evaluate auraptene as an anti-T
      lymphocyte proliferation agent using CD3/CD28-activated lymphocytes isolated from
      C57BL/6 mice. We found that administration of auraptene inhibited CD3/CD28
      activated lymphocyte proliferation in a dose dependent manner, but the inhibition
      at a wide range of doses used in this study did not induce cytotoxicity or
      apoptosis. In addition, auraptene dose dependently decreased the CD3/CD28
      activated T lymphocyte secreting T helper (Th)1 cytokines (interleukin (IL)-2 and
      interferon (IFN)-gamma); whereas, auraptene could decrease Th2 cytokine (IL-4) at
      a higher level (40uM) but had not at lower levels (10 and 20uM). Further
      mechanistic study demonstrated that auraptene doses dependently suppressed T cell
      early and middle/late activation marker CD69 and CD25 expression, respectively.
      Finally, auraptene could suppress cell cycle progression which contributes to
      inhibiting T cell proliferation and cell division. These findings indicate that
      auraptene exhibits anti-inflammatory properties via inhibiting T cell
      proliferation and their inflammatory cytokine secretion that may mediate the
      interaction between T cells and autoimmune disorders, suggesting that auraptene
      is a potential food-derived compound with a benefit to those with abnormally over
      activation T cell mediated response and chronic inflammation such as autoimmune
      and inflammatory diseases. 

PMID- 25620132
TI  - Effects of ginsenoside Rb1 on hypertrophic scar remodeling in rabbit model.
AB  - Ginsenoside, one of the active compounds in Panax ginseng, inhibits tumor growth
      factor-beta 1 (TGF-beta1) and reduces the level of collagen type 1. Ginsenoside
      Rb1 promotes burn wound healing. Our study evaluated the effects of ginsenoside
      Rb1 on hypertrophic scar remodeling. A total of 72 hypertrophic scars were
      generated on the ears of six New Zealand white rabbits. Treatment groups were
      administered with intradermal injections of ginsenoside Rb1 at various amounts
      (0.07mg, 0.28mg and 0.56mg), and evaluated on postoperative Day 35. Scar
      elevation index was used as a quantitative measure, and picrosirius staining of
      histological sections was used to assess collagen arrangement. We determined
      relative mRNA expression of collagen type 1 as well as scar related factors;
      matrix metalloproteinase 2 (MMP2), tissue-inhibitor of metalloproteinase 1
      (TIMP1), alpha-smooth muscle actin (alpha-SMA), and TGF-beta1.
      Immunohistochemistry assays were performed additionally. Application of 0.56mg of
      ginsenoside Rb1 resulted in significant decrement of scar elevation index, in
      comparison with control and lower dosage groups, furthermore achieved broader and
      randomly arranged collagen fibers resembling findings in normal dermis.
      Ginsenoside Rb1 concentration inversely correlated with the mRNA expression and
      immunohistochemical reactivity of scar related factors; MMP2, TIMP1, alpha-SMA,
      and TGF-beta1. In addition, ginsenoside Rb1 suppressed collagen type 1
      expression. Ginsenoside Rb1 is therapeutic in hypertrophic scar remodeling with
      the highest efficacy at 0.56mg of dosage. Ginsenoside Rb1 demonstrated inhibitory
      effects on hypertrophic scar in quantitative and histologic analysis. Further
      research is needed to determine optimal ginsenoside Rb1 application and exposure
      conditions. 

PMID- 25620133
TI  - KS370G, a caffeamide derivative, attenuates unilateral ureteral obstruction
      induced renal fibrosis by the reduction of inflammation and oxidative stress in
      mice.
AB  - Unilateral ureteral obstruction (UUO) is an established animal model used to
      study renal nephropathy. Caffeic acid phenethyl ester, a natural phenolic
      compound, possesses antifibrotic, anti-inflammation and anti-oxidative stress
      effects; however, rapid decomposition by esterases substantially decreases its
      bioavailability. The goal of this study was to investigate the beneficial effects
      of KS370G, a synthetic caffeamide derivative, on UUO-induced renal injury.
      Following the UUO, KS370G (10mg/kg) was administered by oral gavage once a day.
      Renal injury was analyzed at 14 days post-operation. Our results show that KS370G
      significantly attenuated collagen deposition in the obstructed kidney and
      inhibited UUO-induced renal fibrosis markers expression, including fibronectin,
      type I collagen, vimentin, and alpha-smooth muscle actin (alpha-SMA). KS370G
      significantly lowered the expression of renal inflammatory chemokines/adhesion
      molecules and monocyte cells marker (MCP-1, VCAM-1, ICAM-1 and CD11b). KS370G
      also reduced renal malondialdehyde levels and reversed the expression of renal
      antioxidant enzymes (SOD and catalase) after UUO. Furthermore, KS370G
      significantly inhibited UUO-induced elevated plasma AngII and TGF-beta1 levels,
      TGF-beta1 protein expression and Smad3 phosphorylation. These findings
      demonstrate that KS370G reduces renal obstructive nephropathy by possibly
      inhibiting AngII, TGF-beta and Smad3 signaling pathways. 

PMID- 25620134
TI  - Sex differences in the role of transient receptor potential (TRP) channels in
      endothelium-dependent vasorelaxation in porcine isolated coronary arteries.
AB  - Endothelial and smooth muscle Transient Receptor Potential (TRP) channels
      contribute to regulation of vascular tone. We have previously reported sex
      differences in the endothelial function in porcine isolated coronary arteries
      (PCAs). The present study examined the role of TRP channels in endothelium
      dependent and H2O2-induced vasorelaxations in male and female PCAs. Distal PCAs
      were mounted in a wire myograph and precontracted with U46619. Concentration
      response curves to bradykinin, H2O2 and A23187 were constructed in the presence
      of TRP channel antagonists with or without L-NAME and indomethacin to inhibit NO
      synthase and cyclooxygenase respectively. 2-APB (TRPC & TRPM antagonist)
      inhibited the maximum relaxation (Rmax) of the bradykinin-induced vasorelaxation
      and abolished the EDH-type response in PCAs from both sexes. SKF96365 (TRPC
      antagonist) inhibited the Rmax of bradykinin-induced vasorelaxation in males, and
      inhibited Rmax of the EDH-type response in both sexes. Pyr3 (TRPC3 antagonist)
      inhibited both the NO and EDH components of the bradykinin-induced vasorelaxation
      in males, but not females. RN1734 (TRPV4 antagonist) reduced the potency of the
      NO component of the bradykinin-induced vasorelaxation in females only, but
      inhibited the Rmax of the EDH-type component in both sexes. 2-APB, SKF96365 and
      RN1734 all reduced the H2O2-induced vasorelaxation, whereas Pyr3 had no effect.
      No differences in expression level of TRPC3 and TRPV4 between sexes were detected
      using Western blot. Present study demonstrated a clear sex differences in the
      role TRP channels where TRPC3 play a role in the NO- and EDH-type response in
      males and TRPV4 play a role in the NO-mediated response in females. 

PMID- 25620135
TI  - Endostatin stimulates proliferation and migration of adult rat cardiac
      fibroblasts through PI3K/Akt pathway.
AB  - Endostatin, a non-collagenous fragment of type XVIII collagen, has anti
      angiogenic roles. Although the expression level of endostatin increases in some
      experimental models of cardiac diseases, its effects on cardiac remodeling have
      not been clarified. In this study, we investigated the effect of endostatin on
      proliferation, migration and collagen synthesis of cardiac fibroblasts, which are
      activated during the cardiac remodeling following myocardial infarction. Cardiac
      fibroblasts were isolated from adult male Wistar rats and treated with
      recombinant endostatin for 20min to 24h. Cell counting assay was used to
      determine a cell proliferation. Boyden chamber assay was performed to determine a
      cell migration. Wound-healing assay was performed for detecting a wound-induced
      migration. Expression of collagen type I and phosphorylation of Akt,
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and
      p38 mitogen-activated protein kinase (MAPK) were detected by Western blotting.
      Endostatin (100-3000ng/ml) stimulated cell proliferation, migration and wound
      induced migration but not collagen type I expression. Endostatin stimulated
      phosphorylation of Akt (Ser473) but not ERK, JNK and p38 MAPK. LY294002 (10MUM),
      a PI3K/Akt pathway inhibitor, significantly inhibited the endostatin-induced
      proliferation and migration. N-acetyl-l-cysteine (NAC) (5mM), an antioxidant,
      significantly inhibited the endostatin-induced Akt phosphorylation. This study
      for the first time demonstrated that endostatin stimulates cell proliferation,
      migration and wound-induced migration of adult rat cardiac fibroblasts at least
      partly through the reactive oxygen species-dependent activation of Akt. Our
      findings suggest a novel function of endostatin except for an anti-angiogenic
      activity during the wound-healing process following myocardial infarction. 

PMID- 25620136
TI  - Nimbolide inhibits invasion of breast cancer.

PMID- 25620138
TI  - Are intraoperative anesthesia handovers associated with harm? Getting to the
      heart of the matter in cardiac surgery: the search for the hat-trick of quality,
      safety, and continuous improvement.

PMID- 25620137
TI  - A systematic review and comparison of questionnaires in the management of spinal
      cord injury, multiple sclerosis and the neurogenic bladder.
AB  - AIMS: Validated questionnaires are increasingly the preferred method used to
      obtain historical information. Specialized questionnaires exist validated for
      patients with neurogenic disease including neurogenic bladder. Those currently
      available are systematically reviewed and their potential for clinical and
      research use are described. METHODS: A systematic search via Medline and PubMed
      using the key terms questionnaire(s) crossed with Multiple Sclerosis (MS) and
      Spinal Cord Injury (SCI) for the years 1946 to January 22, 2014 inclusive.
      Additional articles were selected from review of references in the publications
      identified. Only peer reviewed articles published in English were included.
      RESULTS: 18 questionnaires exist validated for patients with neurogenic bladder;
      14 related to MS, 3 for SCI, and 1 for neurogenic bladder in general; with 4
      cross-validated in both MS and SCI. All 18 are validated for both male and female
      patients; 59% are available only in English. The domains of psychological impact
      and physical function are represented in 71% and 76% of questionnaires,
      respectively. None for the female population included elements to measure
      symptoms of prolapse. CONCLUSION: The last decade has seen an expansion of
      validated questionnaires to document bladder symptoms in neurogenic disease.
      Disease specific instruments are available for incorporation into the clinical
      setting for MS and SCI patients with neurogenic bladder. The availability of
      caregiver and interview options enhances suitability in clinical practice as they
      can be adapted to various extents of disability. Future developments should
      include expanded language validation to the top 10 global languages reported by
      the World Health Organization.

PMID- 25620139
TI  - Prolonged mechanical ventilation after CABG: risk factor analysis.
AB  - OBJECTIVE: Prolonged ventilation (PV) after coronary artery bypass graft (CABG)
      surgery is a common postoperative complication. Preoperative and operative
      parameters were evaluated in order to identify the patients at risk for prolonged
      ventilation postoperatively in coronary artery bypass graft (CABG) patients.
      DESIGN: Retrospective. SETTING: Research and training hospital, single
      institution. PARTICIPANTS: The authors analyzed the prospectively collected data
      of 830 on- and off-pump coronary bypass patients. INTERVENTIONS: The
      relationships of PV (>24 hours) with preoperative and operative parameters were
      evaluated with logistic regression analysis. MEASUREMENTS AND MAIN RESULTS: Forty
      six patients (5.6%) required PV postoperatively. Hospital mortality was
      significantly higher in this group (45.7% v 4.0%; p = 0.0001). Univariate
      analysis showed that these patients were older (65.6+/-9.3 v 60.4+/-9.9; p =
      0.001), had higher incidences of cerebrovascular disease (21.7% v 10.5%; p =
      0.032), advanced ASA (58.7% v 41.8%; p = 0.026) and NYHA classes (32.6% v 12.2%;
      p = 0.001), and chronic renal dysfunction (20.0% v 4.0%; p = 0.0001). Concomitant
      procedures were more commonly performed in these patients (30.4% v 7.8%; p =
      0.0001), and total durations of perfusion were longer (147.2+/-69.1 v 95.7+/-33.9
      minutes; p = 0.0001). In regression analysis, advanced NYHA class (odds ratio =
      8.2; 95% CI = 1.5-43.5; p = 0.015), chronic renal dysfunction (odds ratio = 7.7;
      95% CI = 1.3-47.6; p = 0.027), and longer perfusion durations (p = 0.012) were
      found to be independently associated with delayed weaning from the ventilator.
      Every 1-minute increase over 82.5 minutes of cardiopulmonary bypass increased
      risk of delayed extubation by 3.5% (95% CI = 0.8%-6.4%). CONCLUSIONS:
      Postoperative prolonged ventilation is associated with advanced NYHA class,
      chronic renal dysfunction and longer perfusion times in CABG patients.

PMID- 25620140
TI  - Modified rapid shallow breathing index adjusted with anthropometric parameters
      increases predictive power for extubation failure compared with the unmodified
      index in postcardiac surgery patients.
AB  - OBJECTIVE: The aim of this study was to determine the best predictors of
      successful extubation after cardiac surgery, by modifying the rapid shallow
      breathing index (RSBI) based on patients' anthropometric parameters. DESIGN:
      Single-center prospective observational study. SETTING: Two general intensive
      care units at a single research institute. PARTICIPANTS: Patients who had
      undergone uncomplicated cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: The following parameters were investigated in conjunction with
      modification of the RSBI: Actual body weight (ABW), predicted body weight, ideal
      body weight, body mass index (BMI), and body surface area. Using the first set of
      patient data, RSBI threshold and modified RSBI for extubation failure were
      determined (threshold value; RSBI: 77 breaths/min (bpm)/L, RSBI adjusted with
      ABW: 5.0 bpm*kg/mL, RSBI adjusted with BMI: 2.0 bpm*BMI/mL). These threshold
      values for RSBI and RSBI adjusted with ABW or BMI were validated using the second
      set of patient data. Sensitivity values for RSBI, RSBI modified with ABW, and
      RSBI modified with BMI were 91%, 100%, and 100%, respectively. The corresponding
      specificity values were 89%, 92%, and 93%, and the corresponding receiver
      operator characteristic values were 0.951, 0.977, and 0.980, respectively.
      CONCLUSIONS: Modified RSBI adjusted based on ABW or BMI has greater predictive
      power than conventional RSBI.

PMID- 25620141
TI  - Questionable benefit of the pulmonary artery catheter after cardiac surgery in
      high-risk patients.
AB  - OBJECTIVE: The aim of this study was to determine the effect of pulmonary artery
      catheterization on clinical outcomes after cardiac surgery in higher-risk
      patients. DESIGN: Retrospective national database analysis. SETTING: U.S.
      hospitals. PARTICIPANTS: A weighted sample of 2,063,337 patients undergoing
      cardiac surgery identified from the Nationwide Inpatient Sample (NIS) from
      January 1, 2000 to December 31, 2010. INTERVENTIONS: Pulmonary artery
      catheterization. MEASUREMENTS AND MAIN RESULTS: Compared to patients who did not
      receive a pulmonary artery catheter, those who did on the whole were on average
      slightly older (66.6+/-11.9 years v 65.5+/-12.8 years, p<0.001), more likely to
      have pulmonary hypertension (7.5% v 5.1%, p<0.001), chronic obstructive pulmonary
      disease (24.6% v 20.7%, p<0.001), obesity (15.0% v 13.1%, p<0.001), and chronic
      renal failure (10.9% v 9.2%, p<0.001). In multivariate analysis, the risk of
      operative mortality in patients who underwent pulmonary artery catheterization
      was significantly higher than in those who did not (4.6% v 3.1%, p<0.001),
      adjusted OR 1.34 (95% CI 1.26-1.43, p<0.001). In propensity matched subgroup
      analysis operative mortality risk was higher in octogenarian patients (OR 1.24, p
      = 0.24), and patients with congestive heart failure (OR 1.39, p = 0.023) who
      underwent pulmonary artery catheterization. No significant difference in
      operative mortality was observed in low-risk patients according to whether or not
      they underwent pulmonary artery catheterization. The incidence of prolonged
      mechanical ventilation and length of stay>30 days was higher in patients who
      underwent pulmonary artery catheterization in all subgroups. CONCLUSIONS: In
      contemporary practice pulmonary artery catheters do not appear to be associated
      with reductions in operative mortality or morbidity and are associated with
      increases in duration of ventilation and length of stay in the intensive care
      unit.

PMID- 25620142
TI  - Preoperative statin therapy decreases early mortality in patients undergoing
      isolated valve surgery: result from a meta-analysis.
AB  - OBJECTIVE: The purpose of this meta-analysis was to assess the role of
      preoperative statin therapy on adverse cardiovascular events in patients
      undergoing valve surgery. DESIGN: Meta-analysis of 10 observational studies.
      SETTING: Hospital. PARTICIPANTS: 22,158 patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The Medline, Cochrane, and Embase databases were
      searched for clinical studies published up to June 2014. Studies that evaluated
      the effects of preoperative statin therapy on valve surgery were included. After
      a literature search in the major databases, 10 observational studies with 22,518
      patients were identified. Pool analysis indicated that preoperative statin
      therapy was associated with a significantly lower risk of early all-cause
      mortality (Odds ratio [OR]: 0.69; 95% confidence interval [CI] 0.50-0.95, p =
      0.03). The benefits of preoperative statin therapy were more obvious in studies
      with isolated valve surgery, resulting in a 1.9% absolute risk and a 38% odds
      reduction of early mortality (2.4 v 4.3%; OR: 0.62; 95% CI 0.49-0.77, p<0.0001).
      A significant reduction by statin therapy also was observed for atrial
      fibrillation (OR 0.88, 95% CI: 0.80-0.98, p = 0.02). However, statin therapy was
      not associated with a lower risk of postoperative stroke (OR: 0.74; 95% CI 0.46
      1.19, p = 0.21), myocardial infarction (OR: 1.02; 95% CI 0.78-1.34, p = 0.87),
      and renal failure (OR: 0.91; 95% CI 0.57-1.44, p = 0.68). CONCLUSIONS:
      Preoperative statin therapy was associated with a significantly lower risk of
      early mortality in patients undergoing isolated valve surgery. A prospective,
      randomized, controlled trial is warranted.

PMID- 25620143
TI  - Transcatheter aortic valve implantation and intraoperative left ventricular
      function: a myocardial tissue Doppler imaging study.
AB  - OBJECTIVE: Transcatheter aortic valve implantation in patients turned down for
      surgical aortic valve replacement is a high-risk procedure. Severe aortic
      stenosis is associated with impaired left ventricular longitudinal motion, and
      myocardial peak systolic velocity is a measure of left ventricular function in
      these patients. The present study aimed to quantify the acute changes in left
      ventricular function during the procedure by using myocardial tissue Doppler
      imaging and transthoracic cardiac output measurements. DESIGN: Prospective
      observational study. SETTING: Tertiary care university hospital. PARTICIPANTS: 40
      patients with severe aortic stenosis scheduled for transcatheter aortic valve
      implantation. INTERVENTIONS: Transesophageal 4-chamber and 2-chamber
      echocardiograms were performed immediately before and ~15 minutes after valve
      implantation. Longitudinal myocardial peak systolic velocity was obtained by
      tissue Doppler imaging from 8 basal segments and averaged. Cardiac output was
      measured by the lithium dilution method, and systemic vascular resistance index
      and stroke volume were calculated. MEASUREMENTS AND MAIN RESULTS: Longitudinal
      myocardial peak systolic velocity improved immediately after valve implantation,
      from -2.3+/-0.8 to -3.0+/-1.1 cm/sec (p<0.001); this represented an average
      increase of 31%+/-33%. Cardiac output increased from 3.2+/-0.8 L/min to 3.6+/-0.9
      L/min (15%+/-33%; p = 0.04). This was due to increased heart rate (59+/-9
      beats/min to 72+/-12 beats/min; p<0.001) and not to an improved stroke volume.
      Systemic vascular resistance index was reduced from 2,937+/-984
      dynes*sec/cm(5)/m(2) to 2,436+/-730 dynes*sec/cm(5)/m(2) (p = 0.003). CONCLUSION:
      Intraoperative echocardiography tissue Doppler imaging detected immediate
      improvement in left ventricular long-axis motion after transcatheter aortic valve
      implantation. The method provided detailed information not obtainable by routine
      hemodynamic monitoring.

PMID- 25620144
TI  - Neurologic injury and protection in adult cardiac and aortic surgery.

PMID- 25620145
TI  - Lung ultrasound in the intensive care unit.

PMID- 25620146
TI  - CASE 1--2015: left ventricular assist device insertion in a patient with heparin
      induced thrombocytopenia and renal failure.

PMID- 25620147
TI  - The functional aortic annulus in the 3D era: focus on transcatheter aortic valve
      replacement for the perioperative echocardiographer.
AB  - The functional aortic annulus represents a sound clinical framework for
      understanding the components of the aortic root complex. Recent three-dimensional
      imaging analysis has demonstrated that the aortic annulus frequently is
      elliptical rather than circular. Comprehensive three-dimensional quantification
      of this aortic annular geometry by transesophageal echocardiography and/or
      multidetector computed tomography is essential to guide precise prosthesis sizing
      in transcatheter aortic valve replacement to minimize paravalvular leak for
      optimal clinical outcome. Furthermore, three-dimensional transesophageal
      echocardiography accurately can quantify additional parameters of the functional
      aortic annulus such as coronary height for complete sizing profiles for all valve
      types in transcatheter aortic valve replacement. Although it is maturing rapidly
      as a clinical imaging modality, its role in transcatheter aortic valve
      replacement is seen best as complementary to multidetector computed tomography in
      a multidisciplinary heart team model. 

PMID- 25620148
TI  - Edible model of mitral valve leaflet surface geometry.

PMID- 25620149
TI  - Simply filling pericardial space with sodium chloride 0.9% enhances
      transesophageal echocardiographic imaging during cardiac displacement for off
      pump coronary artery bypass graft surgery.

PMID- 25620150
TI  - Response to Ellouze et al: "Simply filling pericardial space with sodium chloride
      0.9% enhances transesophageal echocardiographic imaging during cardiac
      displacement for off-pump coronary artery bypass graft surgery".

PMID- 25620151
TI  - Incidence and relevance of nonreentrant monomorphic ventricular tachycardia in
      patients with frequent implantable cardioverter defibrillator interventions.
AB  - BACKGROUND: Nonreentrant ventricular tachycardia (VT) originates in hearts
      without structural disease but occasionally can occur in patients with different
      cardiomyopathies equipped with an implantable cardioverter defibrillator (ICD).
      METHODS: In a series of 142 ICD recipients with structural heart disease
      undergoing ablation for recurrent or incessant monomorphic VT, nonreentrant VTs
      were identified. RESULTS: Nonreentrant VTs were the cause of appropriate ICD
      interventions in 12 patients (8.4%). The underlying heart disease was nonischemic
      cardiomyopathy in eight patients, prior myocardial infarction in two patients,
      and valvular cardiomyopathy in two patients with a mean left ventricular ejection
      fraction of 42 +/- 7%. Unresponsiveness to antitachycardia pacing and repetitive
      spontaneous re-initiation of the VT after defibrillation was the cause of
      frequent ineffective ICD interventions including repetitive ICD shocks in these
      patients. Using ICD interrogation, one or more episodes of a severe electrical
      storm (>=3 serial efficacious ICD shocks within 15 min) were more frequently
      documented in patients with nonreentrant VTs (10/12) than in patients with scar
      related reentrant VTs (36/115). The origin of the nonreentrant VT was the left
      ventricular outflow tract in seven patients, the right ventricular outflow tract
      in three patients, and the tricuspid and mitral annulus in each one patient.
      Catheter ablation including epicardial mapping in 2 patients eliminated the
      nonreentrant VT in 11 of 12 patients and prevented recurrent VT storm.
      CONCLUSIONS: Repetitive nonreentrant VTs may be ineffectively treated by ICD
      interventions and can be the cause of an electrical storm in different
      cardiomyopathies.

PMID- 25620153
TI  - A window into new drug development for urologic oncology. Part I: How bench-to
      bedside research can result in approval.

PMID- 25620152
TI  - Acute conversion of persistent atrial fibrillation during dofetilide loading does
      not predict long-term atrial fibrillation-free survival.
AB  - PURPOSE: Pharmacologic conversion of atrial fibrillation and flutter (AF/AFl) is
      common with dofetilide. We determined whether pharmacologic conversion with
      dofetilide predicts long-term arrhythmia-free survival. METHODS: We
      retrospectively studied a cohort of 264 consecutive patients who initiated
      dofetilide during persistent AF/AFl between 2008 and 2013. Patients were excluded
      if dofetilide was discontinued prior to five doses or electrical cardioversion
      was performed prior to four doses. Incidence of and characteristics associated
      with pharmacologic conversion were determined. Patients were followed for long
      term AF/AFl recurrence. Predictors of recurrence were identified using
      multivariate Cox modeling. RESULTS: Of 205 patients meeting study criteria, 92
      (44.9%) converted to sinus rhythm during dofetilide loading. Female gender,
      history of AFl, greater number of prior catheter ablations, shorter duration of
      current AF/AFl, and presentation in AFl were all associated with acute
      pharmacologic conversion (p = 0.001, 0.05, 0.001, 0.003, and 0.003,
      respectively). In multivariate modeling, longer time since first AF/AFl diagnosis
      (hazard ratio (HR) = 1.07 per 1-year increase, 95% confidence interval (CI) 1.03
      1.10, p < 0.001), longer duration of current AF/AFl episode (HR = 1.01 per 1
      month increase, 95% CI 1.00-1.01, p = 0.003) and greater number of failed
      antiarrhythmic drugs (HR = 1.43 per one drug increase, 95% CI 1.20-1.70, p <
      0.001) were independently associated with shorter time to AF/AFl recurrence.
      Pharmacologic conversion was not significantly associated with time to AF/AFl
      recurrence (HR = 0.79, 95% CI 0.57-1.10, p = 0.2). CONCLUSIONS: Acute
      pharmacologic conversion of persistent AF/AFl to sinus rhythm frequently occurs
      during dofetilide loading. Nevertheless, acute pharmacologic conversion does not
      predict long-term arrhythmia control, which was moderate at best.

PMID- 25620154
TI  - What is the optimal definition of misclassification in patients with very low
      risk prostate cancer eligible for active surveillance? Results from a multi
      institutional series.
AB  - BACKGROUND: The risk of unfavorable prostate cancer in active surveillance (AS)
      candidates is nonnegligible. However, what represents an adverse pathologic
      outcome in this setting is unknown. We aimed at assessing the optimal definition
      of misclassification and its effect on recurrence in AS candidates treated with
      radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 1,710 patients
      eligible for AS according to Prostate Cancer Research International: Active
      Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were
      evaluated. Patients were stratified according to pathology results at RP: organ
      confined disease and pathologic Gleason score <= 6 (group 1); organ-confined
      disease and Gleason score 3+4 (group 2); and non-organ-confined disease, Gleason
      score >= 4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was
      defined as 2 consecutive prostate-specific antigen (PSA) >= 0.2 ng/ml. Kaplan
      Meier curves assessed time to BCR. Multivariable Cox regression analyses tested
      the association between pathologic features and BCR. Multivariable logistic
      regression analyses identified the predictors of adverse pathologic
      characteristics. RESULTS: Overall, 926 (54.2%), 653 (33.0%), and 220 (12.9%)
      patients were categorized in groups 1, 2, and 3, respectively. Median follow-up
      was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3
      had lower BCR-free survival rates compared with those in group 1 (79.1% vs.
      97.0%, P<0.001). No differences were observed between patients included in group
      1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at
      multivariable analyses and after stratification according to margin status. Older
      age and PSA density >= 10 ng/ml/ml were associated with higher risk of
      unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001).
      CONCLUSIONS: Among patients eligible for AS treated with RP, only men with
      Gleason score >= 4+3 or non-organ-confined disease at final pathology were at
      increased risk of BCR. These individuals represent the real misclassified AS
      patients, who can be predicted based on older age and higher PSA density.

PMID- 25620155
TI  - Kinematic effects of a short-term fatigue protocol on punt-kicking performance.
AB  - The punt kick is a fundamental skill used in several team sports; however, there
      has been a lack of research on how fatigue affects its technique. The purpose of
      this study was to determine the effects of short-term fatigue on punt-kicking
      performance. Eight elite and sub-elite Australian Football players performed
      maximal drop punt kicks on their preferred leg prior to, during and after a match
      specific fatigue protocol. Optotrak Certus collected kinematic data from kick
      foot toe-off until ball contact. Repeated-measures analysis of variance showed a
      significant increase in 20 m sprint times after each short-term protocol,
      indicating fatigue. Foot speed did not significantly change with fatigue;
      however, increases in the range of motion at the pelvis and kicking thigh, along
      with increases in kicking thigh angular velocity, occurred. For the support leg,
      maximum knee flexion angular velocity increased while there was greater flexion
      found at the knee and hip, and greater range of motion at the knee. Players are
      able to make kinematic adaptations in order to maintain foot speed while punting
      for maximal distance after short-term efforts. 

PMID- 25620156
TI  - Simultaneous quantification of 25 active constituents in the total flavonoids
      extract from Herba Desmodii Styracifolii by high-performance liquid
      chromatography with electrospray ionization tandem mass spectrometry.
AB  - A sensitive and selective high-performance liquid chromatography coupled with
      electrospray ionization tandem mass spectrometry method has been developed and
      validated for the simultaneous determination of 25 active constituents, including
      21 flavonoids and four phenolic acids in the total flavonoids extract from Herba
      Desmodii Styracifolii for the first time. Among the 25 compounds, seven compounds
      including caffeic acid, acacetin, genistein, genistin, diosmetin, diosmin and
      hesperidin were identified and quantified for the first time in Herba Desmodii
      Styracifolii. Chromatographic separation was accomplished on a ZORBAX SB-C18 (250
      mm*4.6 mm, 5.0 MUm) column using gradient elution of methanol and 0.10/00 acetic
      acid v/v at a flow rate of 1.0 mL/min. The identification and quantification of
      the analytes were achieved using negative electrospray ionization mass
      spectrometry in multiple-reaction monitoring mode. The method was fully validated
      in terms of limits of detection and quantification, linearity, precision and
      accuracy. The results indicated that the developed method is simple, rapid,
      specific and reliable. Furthermore, the developed method was successfully applied
      to quantify the 25 active components in six batches of total flavonoids extract
      from Herba Desmodii Styracifolii. 

PMID- 25620157
TI  - Flexible thermoelectric fabrics based on self-assembled tellurium nanorods with a
      large power factor.
AB  - Highly-flexible thermoelectric fabrics were fabricated based on a layered
      structure, composed of a thin active layer of self-assembled tellurium nanorods
      and a substrate layer of polyvinylidene fluoride. The resulting thermoelectric
      fabrics show a high room temperature power factor of 45.8 MUW m(-1) K(-2), which
      opens a new avenue to fabricate highly-flexible sustainable energy sources. 

PMID- 25620158
TI  - Oculo-facio-cardio-dental (OFCD) syndrome: the first Italian case of BCOR and co
      occurring OTC gene deletion.
AB  - Oculo-facio-cardio-dental (OFCD) syndrome is a rare genetic disorder affecting
      ocular, facial, dental and cardiac systems. The syndrome is an X-linked dominant
      trait and it might be lethal in males. This syndrome is usually caused by
      mutations in the BCL6 interacting co-repressor gene (BCOR). We described a female
      child with mild phenotype of oculo-facio-cardio-dental syndrome. Array
      comparative genomic hybridization (a-CGH) analysis revealed a de novo
      heterozygous deletion in the Xp11.4 region of approximately 2.3 Mb, involving
      BCOR and ornithine carbamoyl-transferase (OTC) genes. The deletion observed was
      subsequently confirmed by real time PCR. In this study we report a first case
      with co-occurrence of BCOR and OTC genes completely deleted in OFCD syndrome.

PMID- 25620159
TI  - Tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) rapidly
      identified a critical missense mutation (P236T) of bovine ACADVL gene affecting
      growth traits.
AB  - Acyl-CoA dehydrogenase, very long chain (ACADVL), encoding ACADVL protein,
      targets the inner mitochondrial membrane where it catalyzes the first step of the
      mitochondrial fatty acid beta-oxidation pathway and plays an important role in
      body metabolism and oxidation of long chain fatty acid releasing energy. Tetra
      primer amplification refractory mutation system PCR (T-ARMS-PCR) is an easy-to
      operate, rapid, inexpensive, and exact method for SNP genotyping. Herein, T-ARMS
      PCR was carried out to detect a critical missense mutation (AC_000176:g.2885C>A;
      Pro236Thr) within the ACADVL gene in 644 individuals from two cattle breeds. In
      order to evaluate the accuracy of the T-ARMS-PCR at this locus, the genotype of
      the sampled individuals was also identified by PCR-RFLP. The concordance between
      these two methods was 98.76%. Statistical analysis showed that the bovine ACADVL
      gene had a significant effect on chest width (P<0.05), chest depth (P<0.05), and
      hip width (P<0.05) in the Qinchuan breed. The cattle with AA genotype had
      superior growth traits compared to cattle with AC and/or CC genotypes. The "A"
      allele had positive effects on growth traits. Therefore, T-ARMS-PCR can replace
      PCR-RFLP for rapid genotyping of this mutation, which could be used as a DNA
      marker for selecting individuals with superior growth traits in the Qinchuan
      breed. These findings contribute to breeding and genetics in beef cattle
      industry.

PMID- 25620160
TI  - Comment to Santos et al., "hyper-IgD and periodic fever syndrome: a new MVK
      mutation (p.R277G) associated with a severe phenotype".
AB  - We performed molecular modeling analysis onto a novel mutation in the gene MVK,
      described by Santos et al., found to be causative of a severe form of Hyper
      IgD/Mevalonate Kinase Deficiency. The mutation p.R277G, in our analysis, lowers
      the binding affinity for some enzyme's substrates. Interestingly, we found that
      p.R277G mutation inhibits binding of Isopentenyl Pyrophosphate (IPP) (binding
      free energy=0 kcal/mol), one of isoprenoids responsible for feedback-inhibition
      of MVK. IPP is known to be an activator of a specific class of T-cells and we can
      hypothesize that increased levels of this metabolite generate an aberrant immune
      system response. Indeed other experiments are needed to verify this hypothesis;
      however, this work demonstrates usefulness of molecular modeling in generating
      novel pathogenic hypothesis.

PMID- 25620161
TI  - Ultrasound use in gynecologic brachytherapy: Time to focus the beam.
AB  - There is wide disparity in the practice of brachytherapy for cervical cancer
      around the world. Although select well-resourced centers advocate use of MRI for
      all insertions, planar X-ray imaging remains the most commonly used imaging
      modality to assess intracavitary implants, particularly where the burden of
      cervical cancer is high. Incorporating soft tissue imaging into brachytherapy
      programs has been shown to improve the technical accuracy of implants, which in
      turn has led to improved local control and decreased toxicity. These improvements
      have a positive effect on the quality of life of patients undergoing
      brachytherapy for cervical cancer. Finding an accessible soft tissue imaging
      modality is essential to enable these improvements to be available to all
      patients. A modality that has good soft tissue imaging capabilities, is widely
      available, portable, and economical, is needed. Ultrasound fulfils these
      requirements and offers the potential of soft tissue image guidance to a much
      wider brachytherapy community. Although use of ultrasound is the standard of care
      in brachytherapy for prostate cancer, it only seems to have limited uptake in
      gynecologic brachytherapy. This article reviews the role of ultrasound in
      gynecologic brachytherapy and highlights the potential applications for use in
      brachytherapy for cervical cancer. 

PMID- 25620162
TI  - Endoscopy-guided brachytherapy for sinonasal and nasopharyngeal recurrences.
AB  - OBJECTIVE/PURPOSE: To evaluate the preliminary results of perioperative endoscopy
      guided brachytherapy (BT) in recurrent sinonasal and nasopharyngeal tumors
      already treated for their primary tumor with a full course of radiotherapy.
      METHODS AND MATERIALS: Patients with recurrence and already treated with a
      previous full course of radiotherapy >65 Gy who underwent BT from December 2010
      to January 2014 were taken into account for this work. Macroscopic disease was
      resected by an endoscopic approach, and catheters for BT were endoscopically
      positioned and fixed at the same time on the surgical bed. Surgery was performed
      under electromagnetic navigation guidance. The irradiation dose was 30 Gy in 12
      fractions, 2.5 Gy each, twice a day, in 6 days. RESULTS: We performed the
      endoscopy-guided BT 11 times in 9 patients; in two cases, no previous radiation
      therapy had been performed; and in one case, followup was too short to be
      considered. A total of 6 patients were eligible for the analysis. One patient
      underwent BT three times because of previous target margin recurrences. There
      were no immediate complications. The median and mean followups were 21 and 19
      months, respectively. The median V90 and V85% were 93% and 95%, respectively. In
      one case, we had a transient deficit of the VI cranial nerve (G3), and in another
      case, we diagnosed a noncomplicated osteonecrosis (G2). The median disease-free
      survival is 12 months, and the median overall survival is 23 months. CONCLUSIONS:
      The combination of endoscopy and BT seems to be a safe option for treating
      recurrent sinonasal and nasopharyngeal tumors.

PMID- 25620163
TI  - Optimizing packing contrast for MRI-based intracavitary brachytherapy planning
      for cervical cancer.
AB  - PURPOSE: We prospectively tested five variations in vaginal gauze packing in an
      effort to improve contrast between the packing, cervix, and applicator for MRI
      based intracavitary brachytherapy planning. METHODS AND MATERIALS: Five patients
      enrolled on a prospective study from May 2013 to October 2013 received MRI-based
      intracavitary brachytherapy for cervical cancer with variations of impregnated
      gauze packing. Substances tested included antibiotic cream alone, antibiotic
      cream mixed with ultrasound gel, conjugated estrogens cream mixed with ultrasound
      gel, ultrasound gel alone, and gadolinium. Images from the T2-weighted pelvic MRI
      were used to obtain signal intensity measurements at points within the packing,
      cervix, and applicator. Signal intensity values were normalized using the signal
      to-noise ratio and compared using an unpaired t-test. RESULTS: Ultrasound gel
      impregnated gauze allowed for the greatest contrast between the packing and the
      cervix with a difference in mean normalized signal intensity of 38.2 (p < 0.01).
      Conjugated estrogens cream mixed with ultrasound gel and gadolinium also provided
      contrast when compared with cervix, with differences in mean normalized signal
      intensity of 25.3 and -16.2, respectively (p < 0.01 for both). For all variations
      but gadolinium, the normalized mean signal intensity of the packing was found to
      be significantly different from the applicator, with the ultrasound gel again
      demonstrating the greatest contrast with a difference of 42.5 (p < 0.01).
      CONCLUSIONS: Gauze impregnated with ultrasound gel, conjugated estrogens cream
      mixed with ultrasound gel, and gadolinium allowed for a significant difference in
      MRI signal intensity between the packing and the cervix. With respect to both the
      cervix and the applicator, ultrasoundgel-impregnated gauze provided the best
      contrast overall.

PMID- 25620164
TI  - Evaluation of our self-designed nanometer silicon membrane sandwich cup system
      for diagnosing tuberculosis.
AB  - BACKGROUND AND AIMS: A nanometer silicon membrane sandwich cup system was self
      designed. It could concentrate the bacilli via 0.45-MUm microporous filter
      membrane and semi-automate the acid-fast bacilli (AFB) by a bacteria-staining
      machine. The aim of the study was to assess the clinical value of our self
      designed system for diagnosing tuberculosis (TB). METHODS: A total of 1993 sputum
      specimens obtained from patients with confirmed or suspected TB were subjected to
      direct or concentrated specimens smear at XiangYa Hospital, Central South
      University between May 2012 and February 2013. In addition, all the specimens
      were also inoculated into Lowenstein-Jensen (L-J) media, and culture results were
      considered as the gold standard for calculating sensitivity and specificity.
      RESULTS: Compared with direct smear examination, an increased density of red
      stained bacilli was observed in the self-designed nanometer silicon membrane
      sandwich cup analysis under the microscope. The positive rate of the self
      designed analysis was significantly higher than that of direct AFB smear [10.9%
      (217/1993) vs 6.2% (123/1993), P < 0.05]. The sensitivity of the self-designed
      system increased (97.3% vs 55.2%, P < 0.05) without a loss of specificity (100%
      vs 100%) for identifying positive TB cases compared with the direct smear method.
      CONCLUSION: The self-designed nanometer silicon membrane sandwich cup and semi
      automatic bacteria-staining machine could more efficiently and rapidly detect the
      AFB in respiratory specimens than direct microscopy. This is a novel and safe
      examination, and it may replace direct smear examination for the diagnosis of
      patients with TB.

PMID- 25620165
TI  - Patterns of care for omission of radiation therapy for elderly women with early
      stage breast cancer receiving hormonal therapy.
AB  - PURPOSE: For well-selected elderly women who undergo segmental mastectomy for
      early-stage, estrogen receptor-positive breast cancer, hormonal therapy alone is
      emerging as an acceptable adjuvant therapy option since the initial publication
      of Cancer and Leukemia Group B 9343 study in 2004 and update in 2013. The rate of
      adoption of adjuvant hormonal therapy alone in lieu of radiation therapy (RT) and
      its associated patterns of care is not known in the United States and was the
      subject of this study. METHODS AND MATERIALS: We used the National Cancer Data
      Base to identify women aged >=70 diagnosed with T1N0/T1Nx invasive breast cancer
      who underwent segmental mastectomy between 1998 and 2011. Because hormone
      receptor status was not specifically and reliably coded, only those who received
      hormonal therapy were included in this analysis. Univariate and multivariable
      exploratory analyses of factors associated with the use of RT were performed
      using SPSS, version 17.0. RESULTS: Of the 182,115 patients who met inclusion
      criteria, 97,530 (53.6%) patients underwent hormonal therapy and were included in
      the analysis. The RT utilization rate in this subset decreased with time from
      84.9% in 1998 to 75.1% in 2011 (P< .001). Multivariable analysis revealed that
      the factors associated with decreased use of RT include (in order of
      association): older age, later year of diagnosis, greater comorbidity score, low
      grade, lack of insurance, treatment at academic facility, race, rural location,
      lower median income, and distance from facility. CONCLUSIONS: This study assesses
      the patterns of care associated with the omission of RT in elderly women with
      early-stage breast cancer who received adjuvant hormonal therapy. Since the
      publication of major clinical trials, this strategy has been increasingly
      adopted. The strongest predictors of using this strategy included advanced
      patient age, high comorbidity score, and low-grade disease.

PMID- 25620166
TI  - Mind-body response and neurophysiological changes during stress and meditation:
      central role of homeostasis.
AB  - Stress profoundly impacts quality of life and may lead to various diseases and
      conditions. Understanding the underlying physiological and neurological processes
      that take place during stress and meditation techniques may be critical for
      effectively treating stress-related diseases. The article examines a hypothetical
      physiological homeostatic response that compares and contrasts changes in central
      and peripheral oscillations during stress and meditation, and relates these to
      changes in the autonomic system and neurological activity. The authors discuss
      how cardiorespiratory synchronization, which occurs during the parasympathetic
      response and meditation, influences and modulates activity and oscillations of
      the brain and autonomic nervous system. Evidence is presented on how
      synchronization of cardiac and respiratory rates during meditation may lead to a
      homeostatic increase in cellular membrane potentials in neurons and other cells
      throughout the body. These potential membrane changes may underlie the reduced
      activity in the amygdala, and other cortical areas during meditation, and
      research examining these changes may foster better understanding of the
      restorative properties and health benefits of meditation. 

PMID- 25620167
TI  - Targeting prostate-specific membrane antigen for personalized therapies in
      prostate cancer: morphologic and molecular backgrounds and future promises.
AB  - Prostate-specific membrane antigen (PSMA) is an integral, non-shed membrane
      glycoprotein that is highly expressed on prostate epithelial cells and strongly
      upregulated in prostate cancer (PCa). Prostatic neoplastic transformation results
      in the transfer of PSMA from the apical membrane to the luminal surface of the
      ducts. However, the role of PSMA in tumor angiogenesis and carcinogenesis is
      poorly understood. PSMA is characterized by folate hydrolase and carboxypeptidase
      activity and internalization function, and its levels are directly correlated to
      androgen independence, metastasis and PCa progression. As largely substantiated
      by preclinical and clinical findings, PSMA could represent a promising target for
      Positron Emission Tomography (PET) radiopharmaceuticals for PCa imaging.
      Furthermore, PSMA could prove an important target for the development of new
      therapeutic approaches, including PSMA-based aptamers, peptides, antibody-drug
      conjugated therapy, as well as radiotherapy and immunotherapy. This review will
      summarize the role of PSMA in PCa development and progression and its potential
      role in the diagnosis and treatment of patients with initial and advanced PCa. 

PMID- 25620168
TI  - Can probiotic administration during pregnancy and the first year of life
      effectively reduce the risk of infections and allergic diseases in childhood?
AB  - Infections and allergic disorders are common pediatric diseases. It has been
      reported that probiotics, which are live microorganisms, confer health benefits
      to hosts when administered in appropriate amounts. Probiotics have been widely
      used in the treatment of pediatric infections and allergic disorders through
      modulating the microbial environment of host. However, it is still not clear
      whether probiotic administration during pregnancy and/or the first year of life
      is an efficient approach for the prevention of infections and allergic diseases
      in childhood. The present study aims to address this question through reviewing
      previous publications on this topic. Analysis of previous studies suggests that
      probiotic administration during pregnancy and/or the first year of life could
      reduce the prevalence of infectious diseases in infancy. The effects of probiotic
      administration during pregnancy and/or the first year of life on the prevention
      of allergic disorders are still not clear. In addition, the available studies
      differ in probiotic species, number of probiotics, dosage of probiotics,
      inclusion and exclusion criteria, outcomes, and diagnostic and follow-up methods.
      These differences highlight further studies for better understanding the effects
      of probiotic administration on the prevention of infections and allergic diseases
      in childhood. 

PMID- 25620169
TI  - Interleukin-33 promotes the proliferation of mouse mast cells through ST2/MyD88
      and p38 MAPK-dependent and Kit-independent pathways.
AB  - Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a
      new modulator of immune and inflammatory responses. Although IL-33 and its
      associated receptor ST2 are reportedly expressed in mast cells (MCs), the precise
      role of IL-33 in modulating MC function has not been determined. In the present
      studies, we explored IL-33 effects on MCs in vivo and in vitro. IL-33 increased
      the number of peritoneal and skin MCs in vivo. IL-33 also resulted in increased
      proliferation of MCs in vitro, as explored by WST assay. Cell cycle analysis
      further confirmed this result by showing increased G2 cell populations in MCs
      stimulated with IL-33. We found that IL-33-mediated MC proliferation requires ST2
      and MyD88, is independent of Kit, and is mediated through a p38 MAPK-dependent
      pathway. IL-33 did not induce degranulation and was not cytotoxic for MCs. This
      novel mechanism for increasing MC proliferation and numbers further defines the
      role of IL-33 in MC-dependent diseases including allergies and may help to
      develop novel approaches for the treatment of these disorders. 

PMID- 25620170
TI  - Novel mechanism of plasma prekallikrein (PK) activation by vascular smooth muscle
      cells: evidence of the presence of PK activator.
AB  - The contribution of plasma prekallikrein (PK) to vascular remodeling is becoming
      increasingly recognized. Plasma PK is activated when the zymogen PK is digested
      to an active enzyme by activated factor XII (FXII). Here, we present our findings
      that vascular smooth muscle cells (VSMC) activate plasma PK in the absence of
      FXII. Extracted plasma membrane and cytosolic fractions of VSMCs activate PK, but
      the rate of PK activation was greater by the membrane fraction. FXII neutralizing
      antibody did not affect PK activation by extracted proteins of VSMCs. VSMC PKA
      was inhibited by the serine protease inhibitors such as aprotinin,
      phenylmethylsulfonyl fluoride, leupeptin and CTI with CI50 of 0.78 MUM, 1 mM,
      3.13 MUM and 40 nM on the cultured cells, respectively. No inhibition of PK
      activation by cysteine, aspartic acid, and metalloprotease inhibitors was
      observed. This is the first report of the presence of an intrinsic PKA in VSMC.
      Considering that VSMCs are normally separated from the circulating blood by
      endothelial cells, direct PK activation by VSMCs may play a role in disease
      states like diabetes, hyperlipidemia or hypertension where the endothelial layer
      is damaged. 

PMID- 25620171
TI  - Missense variants of the alanine: glyoxylate aminotransferase 2 gene correlated
      with carotid atherosclerosis in the Japanese population.
AB  - Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric
      dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase.
      Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice.
      There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and
      rs16899974) with which AGXT2 activity changes in humans and may be related to
      vulnerability of vascular sclerosis. To examine the relationship between them, we
      studied the functional haplotypes of the AGXT2 gene and decided their
      relationship with arteriosclerotic changes via carotid intima-media thickness
      (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the
      carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A
      haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity
      (P<0.0001; Pearson?s correlation coefficients: 0.497). The C-A-A-A haplotype was
      significantly associated with mean carotid IMT (P=0.049) and max carotid IMT
      (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid
      IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis,
      subjects with two C-A-A-A haplotypes were independently and positively associated
      with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There
      was a significant correlation between the functional variants in the AGXT2 gene
      and carotid IMT in Japanese. The AGXT2 genotype may be an important factor
      underlying atherosclerosis.

PMID- 25620172
TI  - MicroRNA-133a functions as a tumor suppressor in gastric cancer.
AB  - MicroRNAs (miRNAs) are small and highly conserved non-coding RNAs that regulate
      gene expression of target mRNAs through posttranscriptional inhibition involved
      in the tumorigenesis and progression of multiple malignancies. Although miR-133a
      has been shown to function as a tumor suppressor in some cancers, the clinical
      significance and function of miR-133a in gastric cancer remain unclear. Hence, we
      were focused on the expression and mechanisms of miR-133a in the development of
      gastric cancer in this study. It was found that the expression of miR-133a was
      downregulated (P<0.001), while transgelin-2 (TAGLN2) was upregulated (P<0.05) in
      primary gastric cancer tissues, compared to the adjacent non-cancerous tissues
      (ANCT). Furthermore, decreased expression of miR-133a and increased expression of
      TAGLN2 were both associated with lymph node metastases in patients with gastric
      cancer (P<0.001; P=0.011). Functional analysis studies revealed that ectopic
      expression of miR-133a reduced cell proliferation and invasion, and induced cell
      apoptosis and cycle arrest via suppressing the level of TAGLN2 from
      transcriptional and translational levels and downregulated the expression of
      proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2)
      in gastric cancer cells. In conclusion, these results demonstrate that decreased
      expression of miR-133a is associated with the lymph node metastases of patients
      with gastric cancer. Overexpression of miR-133a inhibits cell growth and invasion
      and induces cell apoptosis and cycle arrest through repressing TAGLN2 gene,
      suggesting that miR-133a might be used as a biomarker or therapeutic target for
      the treatment of gastric cancer.

PMID- 25620173
TI  - Study on connexin gene and protein expression and cellular distribution in
      relation to real-time proliferation of porcine granulosa cells.
AB  - Granulosa cells (GCs) play an important role during follicle growth and
      development in preovulatory stage. Moreover, the proteins such as connexins are
      responsible for formation of protein channel between follicular-cumulus cells and
      oocyte. This study was aimed to investigate the role of connexin expression in
      porcine GCs in relation to their cellular distribution and real-time cell
      proliferation. In the present study, porcine GCs were isolated from the follicles
      of puberal gilts and then cultured in a real-time cellular analyzer (RTCA) system
      for 168 h. The expression levels of connexins (Cxs) Cx36, Cx37, Cx40 and Cx43
      mRNA were measured by RQ-PCR analysis, and differences in the expression and
      distribution of Cx30, Cx31, Cx37, Cx43 and Cx45 proteins were analyzed by
      confocal microscopic visualization. We found higher level of Cx36, Cx37, and Cx43
      mRNA expression in GCs at recovery (at 0 h of in vitro culture, IVC) compared to
      all analyzed time periods of IVC (24, 48, 72, 96, 120, 144 and 168 h; P<0.001).
      On the other hand, the expression level of Cx40 transcripts was higher after 24 h
      of IVC compared to 0 h and the other times of IVC (P<0.001). Similarly to mRNAs,
      the expression levels of Cx31, Cx37 and Cx45 proteins were higher before (0 h)
      compared to after 168 h of IVC. The expression of Cx30 and Cx43, however, did not
      vary between the groups. In all, the proteins were distributed throughout the
      cell membrane rather than in the cytoplasm both before and after IVC. After 24 h
      of IVC, we observed a significant increase in the proliferation of GCs (log
      phase). We found differences in the proliferation index between 72-96 and 96- 140
      h within the same population of GCs. In conclusion, the decrease in the
      expression of Cx mRNAs and proteins following IVC could be associated with a
      breakdown in gap-junction connections (GJCs), and leads to the decreased of their
      activity, which may be a reason of non-functional existence of connexon in
      follicular granulosa cells. These data indicated that the differentiation and
      proliferation of GCs and lutein cells are regulated by distinct mechanisms in
      pigs.

PMID- 25620174
TI  - Microarray analysis of inflammatory response-related gene expression in the uteri
      of dogs with pyometra.
AB  - Pyometra, which is accompanied by bacterial contamination of the uterus, is
      defined as a complex disease associated with the activation of several systems,
      including the immune system. The objective of the study was to evaluate the gene
      expression profile in dogs with pyometra compared with those that were clinically
      normal. The study included uteri from 43 mongrel bitches (23 with pyometra, 20
      clinically healthy). RNA used for the microarray study was pooled to four
      separated vials for control and pyometra. A total of 17,138 different transcripts
      were analyzed on the uteri of female dogs with pyometra and of healthy controls.
      From 264 inflammatory response-related transcripts, we found 23 transcripts that
      revealed a 10- to 77-fold increased expression. Thereby, the expression of
      interleukin 8 (IL8), interleukin-1-beta (IL1B), interleukin 18 receptor
      (IL18RAP), interleukin 1-alpha (IL1A), interleukin receptor antagonist (IL1RN)
      and interleukin 6 (IL6) increased 77-, 20-, 17-, 13-, 13- and 11-fold,
      respectively. Furthermore, the expression of the calcium binding proteins S100A8
      was 44-fold higher, and that of S100A12 and S100A9 37-fold, respectively, in the
      uteri of canines with pyometra compared with that of the controls. Moreover, the
      expression of the transcripts of toll-like receptors (TLR8 and TLR2), integrin
      beta 2 (ITGB2), chemokine ligand 3 (CCL3), semaphorin 7A (SEMA7A), CD14 and
      prostaglandin-endoperoxide synthase 2 (PTGS2) was increased between 10- and 18
      fold. Furthermore, after using RT-qPCR we found an increased expression of AOAH,
      IL1A, IL8, CCL3, IL1RN and SERPINE 1 mRNAs which can be served also as markers of
      the occurrence of pyometra in domestic bitches. In summary, it is concluded that
      up-regulation of interleukins may be used as a marker of the inflammatory
      response in dogs with pyometra. Moreover, all of the 23 up-regulated transcripts
      may be novel molecular markers of the pathogenesis of canine pyometra. Several
      proteins--?products of these genes--may be recognized as potential biomarkers of
      this disease or as therapeutic targets in other mammalian species, including
      humans.

PMID- 25620175
TI  - Knockdown of the inflammatory factor pentraxin-3 suppresses growth and invasion
      of lung adenocarcinoma through the AKT and NF-kappa B pathways.
AB  - Pentraxin-3 (PTX3), a modulator of tumor-associated inflammation, is known to be
      positively correlated with tumor grade and severity of malignancies, but the
      function and molecular underlying mechanisms of PTX3 remain unclear. In the
      present study, the expression of PTX3 in human lung adenocarcinoma (LAC) was
      examined by immunohistochemical assay using a tissue microarray procedure. A loss
      of-function experiment was performed to explore the effects of lentiviral vector
      mediated PTX3 shRNA (Lv-shPTX3) on cell growth and invasive potential in LAC cell
      lines (A549 and LETPalpha-2), assessed by MTT and Transwell assays, respectively.
      We found that the expression of PTX3 protein was significantly increased in LAC
      tissues compared with that in adjacent non-cancerous tissues (ANCT) (60.42% vs.
      29.17%, P=0.004), and positively correlated with lymphatic invasion of the tumor
      (P=0.006). Furthermore, knockdown of PTX3 suppressed tumor proliferation and
      invasion of LAC cells, followed by decreased expression of p-AKT, p-NF-kappa B,
      PCNA, and MMP-9. Taken together, our findings demonstrate that upregulation of
      PTX3 expression is correlated with tumor metastasis of LAC patients, and
      knockdown of PTX3 blocks the development of LAC through inhibition of the AKT and
      NF-kappa B pathways, suggesting that PTX3 may serve as a potential therapeutic
      target for the treatment of cancer. 

PMID- 25620176
TI  - Gene expression profiles in three histologic types, clear-cell, endometrioid and
      serous ovarian carcinomas.
AB  - Ovarian carcinoma is the most lethal type of gynecologic malignancy in the
      Western world. Majority of early stage ovarian cancers are asymptomatic and this
      is the main reason that more than two-thirds of patients are diagnosed with
      advanced disease. Ovarian tumors are heterogeneous and the different histologic
      subtypes are further classified as benign, borderline (low-grade) and malignant
      (high-grade) to reflect their behavior. The aim of the study was to analyze gene
      expression profiles in three histologic types of ovarian carcinoma in an attempt
      to find the molecular differences among serous, endometrioid and clear cell
      subtypes. The analysis of gene expression was performed on 57 samples of ovarian
      carcinoma. RNA was isolated from the ovarian cancer tissues. The gene expression
      changes were determined by microarray analysis and quantitative real time
      polymerase chain reaction (qRT-PCR). Measurement of relative gene expression
      levels was used to identify molecular differences among three histologic types of
      ovarian carcinoma (clear-cell, endometrioid and serous). Unsupervised statistical
      analysis revealed four biological subtypes among three histotypes under study.
      The endometrioid ovarian carcinoma was divided into two molecular subtypes. The
      biggest molecular differences were observed between clear-cell and serous
      carcinomas (1070 genes, FDR 0.05), the smallest between endometrioid and serous
      carcinomas (81 genes, FDR 0.05). The biggest group of differentially expressed
      genes was involved in transport and metabolism. This finding can explain the
      differences in the response to chemotherapy observed among different histologic
      types of ovarian carcinomas. In conclusion, we found TCF2 (HNF1B) gene as a
      suitable marker for ovarian clear cell carcinoma. Gene expression profiling also
      shed light on the molecular mechanisms of different chemoresistance among the
      analyzed histotypes. 

PMID- 25620177
TI  - Comparative study on CT perfusion parameters of different types of lung cancer
      before and after chemoradiotherapy.
AB  - The aim of this paper was to observe the changes in computed tomography (CT)
      perfusion parameters of patients with lung cancer in early stage before and after
      chemoradiotherapy. Twenty-five previously treated lung cancer patients underwent
      a first CT perfusion scan and then a following one before the second course of
      chemotherapy. CT images of the fourth course of treatment were compared with the
      initial images. The cases were divided into a remission group and a non-remission
      group according to Response Evaluation Criteria In Solid Tumors (RECIST). Blood
      flow (BF), blood volume (BV), Patlak permeability Surface (PS) and Pallak blood
      volume (PBV) in the different groups were respectively compared before and after
      treatment. In addition, SPSS17.0 was applied for statistical analysis. P less
      than 0.05 signified that the difference had statistical meaning. CT perfusion
      parameters were all found to be changed compared to before the treatment. BV and
      PBV parameters decreased twice. BV and PBV parameters in the non-remission group
      showed an increasing trend. The difference before and after the treatment of
      these parameters had the highest statistical significance, as well as the
      difference of remission rate of PBV increasing group and decreasing group.
      Through the contrasting chi2 test of remission rate of BV and PBV, it was found
      that the remission rate of the BV increasing group and the decreasing group had
      no statistical difference; the remission rate in the PBV decreasing group was
      higher than the increasing group. All the findings suggest that the change in
      size of the damaged tissue had no statistical meaning in the early stage of CT
      perfusion parameter change; CT perfusion parameter of the remission group in the
      early stage after chemotherapy decreased while the non-remission group increased;
      the change of BV and PBV was significant. 

PMID- 25620178
TI  - The mechanism and significance of E-cadherin, anti-apoptosis B-cell lymphoma-2
      protein and sE-cadherin roles in cancer.
AB  - Women are most likely to suffer from breast cancer of all the malignant tumors.
      Its incidence is growing rapidly, which severely threatens the health of females.
      E-cadherin (E-cad), as the mediator of tumor tissue cells, when adhesion between
      the cells decreases, can improve the wettability and migration ability of cells,
      and help cell growth and proliferation in the new area. E-cad serves not only as
      a cancer inhibitor but also as a cancer promoter. sE-cadherin (sE-cad) is formed
      as a result of the degradation and exfoliation of N-end extracellular domain of E
      cad and its level is closely related to the invasion and metastasis of tumor
      cells. B-cell lymphoma-2 protein (Bcl-2 protein) is the key regulatory factor for
      the mitochondria apoptosis pathway during the apoptosis of cells, and it plays an
      important role in the signal transduction pathway of cell apoptosis. Its abnormal
      expression may induce disorder of the mechanism. This paper, through the study of
      the expression and relationship of E-cad, Bcl-2 protein and sE-cad, attempts to
      explain their expression changes during the development of breast cancer,
      providing clues clinically useful for further recognition of occurrence and
      development, early diagnosis, interference and early treatment of breast cancer. 

PMID- 25620179
TI  - Profile of select hepatic insulin signaling pathway genes in response to 2
      aminoanthracene dietary ingestion.
AB  - Some genes that regulate various processes such as insulin signaling, glucose
      metabolism, fatty acid, and lipid biosynthesis were profiled. The objective of
      the current investigation is to examine the mRNA expression of some genes that
      mediate insulin signaling due to 2AA toxicity. 2AA is a polycyclic aromatic
      hydrocarbon (PAH) that has been detected in broiled food and tobacco smoke.
      Twenty-four post-weaning 3-4-week-old F344 male rats were exposed to 0 mg/kg
      diet, 50 mg/kg-diet, 75 mg/kg-diet, and 100 mg/kgdiet 2AA for 2 weeks and 4
      weeks. The mRNA expression of AKT1, G6PC, GCK, GLUT4, INSR, IRS1, PP1R3C, PAMPK,
      SOCS 2, and SREBF1 was determined by qRTPCR followed by the quantification of
      G6PC and AMPK via ELISA. The results suggest that 2AA modulates these genes
      depending on the length of exposure. Up-regulation of AMPK and SOCS2 genes in
      animals treated with 100 mg/kg-diet and 50 mg/kg-diet, respectively, during 14
      days of feeding was noted. G6PC expression was inhibited in the 2-week group
      while being dose-dependently increased in the 4-week group. Hepatic activity of
      G6PC was enhanced significantly in the livers of rats that ingested 2AA. It
      appears that 2AA intoxication leads to the activation of irs1 and akt1 genes in
      the liver. Quantified AMPK amounts increased significantly in the short-term
      treatment group. Dose-dependent rise of AMPK in animals treated to 2AA showed an
      increased production of hepatic AMPK in response to the toxicity of 2AA in order
      to maintain cellular homeostasis. In contrast, the reduction in AMPK
      concentration in treated animals within the 4-week set indicated an adaptive
      recovery.

PMID- 25620180
TI  - Neural correlates of observation of disgusting images in subjects with first
      episode psychosis and post-traumatic stress disorder.
AB  - The aim of this study was to analyze neural responses to disgusting images in
      individuals with first episode psychosis and post-traumatic stress disorder
      (PTSD). Although anhedonia is a common symptom in both disorders we expected that
      they would be associated with different neurophysiological abnormalities and
      patterns of activation. We recruited three groups of participants: 13 individuals
      with first episode psychosis, 10 individuals with PTSD who had survived the April
      2009 L?Aquila earthquake and 25 healthy controls matched for age and education.
      All individuals participated in a functional imaging experiment in which they
      watched six alternating blocks of disgusting and scrambled images whilst
      undergoing scanning with a General Electric 1.5T whole-body scanner. We estimated
      individuals'? beta-weights, extracting 22 clusters corresponding to 22
      significant areas. Findings were consistent with other neuroimaging studies; the
      active areas (i.e. amygdala, insula, inferior and medial frontal gyrus) have
      consistently been associated with emotional experiences. Statistical analysis
      revealed important group differences in intensity and direction (positive or
      negative) of signal from baseline during disgusting condition. Although these
      results are preliminary they show that functional neuroimaging techniques may
      make a valuable contribution to differential diagnosis of first episode psychosis
      and PTSD.

PMID- 25620181
TI  - In vitro expansion of tumour cells derived from blood and tumour tissue is useful
      to redefine personalized treatment in non-small cell lung cancer patients.
AB  - The clinical development of locally and advanced non-small cell lung cancer
      (NSCLC) suffers from a lack of biomarkers as a guide in the selection of optimal
      prognostic prediction. Circulating Tumour Cells (CTCs) are correlated to
      prognosis and show efficacy in cancer monitoring in patients. However, their
      enumeration alone might be inadequate; it might also be critical to understand
      the viability, the apoptotic state and the kinetics of these cells. Here, we
      report what we believe to be a new and selective approach to visually detect
      tumour specific CTCs. Firstly, using labelled human lung cancer cells, we
      detected a specific density interval in which NSCL-CTCs were concentrated.
      Secondly, to better characterize CTCs in respect to their heterogeneous
      composition and tumour reference, blood and tumour biopsy were performed on
      specimens taken from the same patient. The approach consisted in comparing
      phenotype profile of CTCs, and their progenitor Tumour Stem Cells, (TSCs).
      Moreover, NSCL-CTCs were cultivated in short-time human cultures to provide
      response to drug sensitivity. Our bimodal approach allowed to reveal two items.
      Firstly, that one part of a tumour, proximal to the bronchial structure, displays
      a predominance of CD133+. Secondly, specific NSCL-CTCs Epithelial Cell Adhesion
      Molecule (EpCAM)+CD29+ can be used as a negative prognostic factor as well the
      high expression of CTCs EpCAM+. These data were confirmed by drug-sensitivity
      tests, in vitro, and by the survival curves, in vivo.

PMID- 25620182
TI  - Increased risk of osteoporosis in postmenopausal women with type 2 diabetes
      mellitus: a three-year longitudinal study with phalangeal QUS measurements.
AB  - Type 2 diabetes mellitus (T2DM) is associated with a higher risk of fractures
      even in presence of normal or increased bone mineral density. The purpose of this
      three-year longitudinal study was to evaluate the risk of osteoporotic fractures
      by assessing the changes of Quantitative Ultrasound (QUS) parameters in a group
      of postmenopausal women with type 2 diabetes mellitus (T2DM) compared with non
      diabetic controls. The measurements were taken on a group of 18 postmenopausal
      women affected by T2DM and 18 healthy age-matched controls, aged 55-70 years,
      referring to the Osteolab laboratory at the ISBEM Research Institute (Brindisi,
      Italy) between 2009 and 2013. Subjects had baseline and 3-year follow-up
      measurements with phalangeal QUS carried out by a DBM Sonic Bone Profiler 1200
      (Igea(r)); medical history, current drug therapies and risk factors for fractures
      were recorded for each patient. The analyzed phalangeal QUS parameters were
      Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), Fast
      Wave Amplitude (FWA) and Signal Dynamic (SDy). At the baseline visit we found no
      statistically significant difference between T2DM and non-diabetic patients when
      looking at phalangeal QUS parameters. At the three-year follow-up visit, a
      significantly higher decrease of both BTT (P<0.001) and AD-SoS (P<0.001)
      parameters was found in the T2DM group. On the contrary, the decrease of FWA was
      significantly higher in non-diabetic controls (P<0.001). Our data confirm the
      ability of phalangeal QUS to detect differences in the risk of osteoporotic
      fractures in T2DM postmenopausal women compared to non-diabetic controls. The
      study suggests that T2DM women present a higher cortical porosity and increased
      trabecular bone density compared to non-diabetic controls, respectively shown by
      the higher decrease of both AD-SoS and BTT and the lower decrease of FWA.

PMID- 25620183
TI  - Inhibitory effects of different lactobacilli on Candida albicans hyphal formation
      and biofilm development.
AB  - The aim of this study was to investigate the effects of different species of
      Lactobacilli on hyphal formation and biofilm development by the opportunistic
      fungal pathogen Candida albicans. We employed 4 different Lactobacillus species,
      namely L. rhamnosus, L. acidophilus, L. plantarum and L. reuteri, and 2 C.
      albicans strains, the reference DAY286 and its isogenic hwp1/hwp1 mutant, the
      FJS24 strain. As assessed by morphological analysis and quantitative colorimetric
      assays, Lactobacillus crude filtrate supernatant fluids (CFSF) affected Candida,
      impairing both hyphal formation and biofilm production. The CFSF-mediated
      phenomenon occurred in a dilution- and time-dependent manner and was consistently
      observed, irrespective of the C. albicans HWP1 genotype. 

PMID- 25620184
TI  - The immunomodulatory molecule pidotimod induces the expression of the NOD-like
      receptor NLRP12 and attenuates TLR-induced inflammation.
AB  - Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid) (PDT) is a
      synthetic dipeptide with in vitro and in vivo immunomodulatory properties that is
      largely used for treatment and prevention of infections in paediatric and disease
      prone patients. However, the effects of PDT on cellular immune responses are
      still poorly characterized and there is little information on the mechanism of
      action of this compound. It has been speculated that PDT action may be exerted
      through the interaction with a Pattern Recognition Receptor (PRR). Therefore, to
      gain a further understanding of the immune pathways involved by PDT, we first
      decided to investigate whether PDT could modify the immune response triggered by
      TLR ligands. Monocytic cells were exposed to PDT then stimulated with a panel of
      TLR agonists. Under these experimental conditions, we observed a significant
      decrease in the synthesis of key proinflammatory mediators in comparison to the
      production observed in TLR-stimulated cells that were not treated with PDT. Using
      RT2 Profiler PCR Array we have observed that PDT specifically up-regulates the
      expression of the NOD-like receptor NLRP12 mRNA in the absence of any further
      costimulation. Increase of NLRP12 in cells treated with PDT was confirmed using
      specifically designed real-time quantitative PCR and western blotting assays
      where a clear increase in the amount of NLRP12 protein was detected. Furthermore,
      in myeloid/monocytic cells we demonstrated that PDT treatment counteracts the
      NLRP12 reduction induced by TLR agonists. Finally, the results obtained using
      NLRP12 silenced cells showed that down-regulation of the proinflammatory function
      occurring in PDT-treated cells upon interaction with TLRs is associated with the
      increased levels of NLRP12 induced by PDT. To our knowledge this is the first
      evidence of an immunomodulatory peptide that upregulates NLRP12 and, through this
      molecule, antagonizes the TLR-induced inflammatory response. These results pave
      the way for the development of innovative therapeutic approaches aimed at
      controlling different pathological settings such as tumorigenesis, systemic
      inflammatory processes and autoimmunity, where NLRP12 plays a crucial role. 

PMID- 25620185
TI  - Nitric oxide synthase evaluation in oral precancerous and cancerous lesions.
AB  - Nitric Oxide (NO) has been linked to several cardiovascular, neurological and
      immunological physiological and pathological functions. Several studies have
      shown that the eNOS, nNOS and iNOS effects on cancer cell growth and
      proliferation are related to the upregulation of the Wnt pathway and have a
      central role during metastasis development. Recent studies suggest that cancer
      cells undergo metabolic reprogramming, which drives cancer cell growth and
      progression. The aim of this study was to observe the NOS activity in the
      pathogenesis of oral precancerous and cancerous lesions. The results showed
      changes in eNOS activity levels, which increased from healthy oral mucosa to oral
      squamous cell carcinoma SCC, through different dysplasia levels. The iNOS
      activity levels increased in precancerous lesions compared to healthy mucosa,
      where iNOS was absent, while it decreased in SCC lesions. Moreover, a gradual
      increase of nNOS activity together with the progression of the lesions was also
      found. These results may suggest how NO could play a critical role during
      pathogenesis, growth and development of precancerous lesions to cancer
      degeneration. 

PMID- 25620186
TI  - A natural formulation (imoviral?) increases macrophage resistance to LPS-induced
      oxidative and inflammatory stress in vitro.
AB  - Imoviral? is a natural product formulation containing a mixture of uncaria,
      shiitake and ribes extracts. All ingredients are recognized as antioxidant, anti
      inflammatory agent and immunomodulant. In order to evaluate the rational basis of
      extract mixture as immunomodulatory agent, we tested the effect of Imoviral?
      formulation on macrophage response to lipopolysaccharide (LPS)-induced stress.
      The effect was evaluated as variation of reactive oxygen species (ROS) and
      prostaglandin E2 (PGE2) production and as cytokine gene expression. The extract
      did not affect cell viability up to 250 MUg/ml. Treatment with extract (10-150
      MUg/ml) reduced ROS and PGE2 production as well as IL-8 and TNF-alpha gene
      expression. A pre-treatment with extract blunted LPS-induced production of ROS
      and PGE2, markers of oxidative and inflammatory stress, as well as the gene
      expression of all cytokines tested, indicators, in vitro, of immune response
      activation. In conclusion, we demonstrated that Imoviral? formulation could be a
      useful tool to modulate the immune function, reducing the oxidative and
      inflammatory markers related to bacterial attack. Experimental data suggest that
      Imoviral? extract mixture could also represent a preventive pharmacological
      strategy to enhance cell resistance to bacterial infections.

PMID- 25620187
TI  - Sarcoid-like pattern in a patient with tuberculosis.
AB  - For several decades the ?mystery? of sarcoidosis has continued to evade
      revelation. Nowadays, due to medical progress and the opportunity of performing
      highly specialized tests which assist the identification of this condition as a
      separate disease, the understanding of the eternal mystery appears closer.
      Nevertheless, many contemporary studies focus on the putative link between
      sarcoidosis and infectious antigens isolated from skin lesions. On the other
      hand, a golden rule to differentiate sarcoidosis from other conditions such as
      tuberculosis and sarcoid-like reactions is the sterility of granulomas. However,
      there are hypotheses which state that sarcoidosis could be related to
      tuberculosis and, in particular, to the Mycobacterium species. The similarities
      that many authors identify between the genetic signatures of the two conditions
      definitely raise concerns regarding: i) the inability to categorize every single
      case in a clear-cut way, namely in inflammatory/autoimmune or infectious; ii) the
      need of new criteria to clearly differentiate sarcoid-type reactions in the
      context of infectious diseases from sarcoidosis as an autonomous disease. We
      report the case of a 35-year-old male patient with histopathological evidence of
      sarcoid-like granulomas in cutaneous lesions on the face and imaging studies
      consistent with a systemic form of sarcoidosis. However, a positive QuantiFERON
      TB Gold test and Ziehl-Neelsen staining was found, leading to the diagnosis of a
      rare case of TBC with histopathological evidence of sarcoid-like lesions. The
      following are also discussed: i) the potential role of tuberculosis antigens in
      the context of occult tuberculosis as generators of sarcoid-type of reaction; and
      ii) the necessity of additional diagnostic panels as a standard procedure in
      patients with suspected sarcoid granulomas of unknown origin. 

PMID- 25620188
TI  - Macrophages and dendritic cells in the development of liver injury leading to
      liver failure.
AB  - Liver failure (LF) continues to be a serious problem due to different underlying
      disorders. Not only hepatocytes but Kupffer cells (KCs) and dendritic cells (DCs)
      are of importance in this instance. We wanted to investigate the possible role of
      KCs and liver DCs in the development of liver injury in patients with liver
      failure. Liver specimens from 23 patients who died after liver failure were
      examined for the presence and distribution of CD68-positive KCs and CD83-positive
      DCs by immunohistochemistry. The distribution of the CD83-positive DC in the
      sinusoidal and the periportal spaces was not even. While 39.1% of patients had a
      high sinusoidal density of CD83-positive cells, 60.9% demonstrated a high density
      of CD83-positive cells in the periportal tract. The number of CD83-positive DCs
      in periportal tracts in patients with advanced liver fibrosis (n=5) were high,
      while those with mild liver fibrosis (n=18) had low numbers of mature dendritic
      cells (chi2=4.107; p=0.043). In addition, all patients with intensive fibrosis
      had low counts of CD68-positive KC?s in portal tracts vs patients with mild
      fibrosis of which 67% had high counts (chi2=6.97; p=0.008). In seven of the
      patients with moderate steatosis (87.5%) low numbers of CD68-positive KCs were
      found in sinusoids, in contrast to those with severe steatosis, where 12 patients
      (80%) had high KC counts (chi2=13.4; p less than 0.001). The distribution and
      number of CD68-positive KC and CD83-positive DC reflect the progression of liver
      fibrosis leading to liver failure.

PMID- 25620189
TI  - Alexithymia and its relationships with acute phase proteins and cytokine release:
      an updated review.
AB  - The alexithymia construct is multidimensional and comprises several features: (a)
      difficulty in identifying and describing feelings, (b) difficulty in
      distinguishing feelings from the bodily sensations, (c) diminution of fantasy,
      and (d) concrete and poorly introspective thinking. Altered immune responses have
      been seen in some psychiatric disorders and several data suggest that analogous
      changes could also be observable in alexithymia. Hence, the aim of this review is
      to investigate the relationships between alexithymia and acute phase proteins and
      cytokines in psychiatric, psychosomatic and medical diseases. Several studies
      have reported an association between alexithymia and higher circulating levels of
      acute phase proteins, especially C-Reactive Protein. Moreover, in alexithymic
      subjects the pro-inflammatory and anti-inflammatory cytokine balance may be tuned
      toward a pro-inflammatory imbalance with a concomitant altered cell-mediated
      immunity. These findings may be consistent with the "?stress-alexithymia
      hypothesis"?. Therefore, the screening of alexithymic traits and the
      administration of appropriate psychological and psychotherapeutical interventions
      should be integral parts of disease management programs. Supplying such
      interventions will probably help with prevention of the development of the
      disease and/or its exacerbation by improving the quality of life of alexithymic
      individuals.

PMID- 25620190
TI  - Expression of poly(ADP-ribose) polymerase in bone regeneration.
AB  - Poly(ADP-ribose) polymerase (PARP) is a 116kDa enzyme catalysing the synthesis of
      ADP-ribose polymers from NAD+. PARP is activated in response to DNA strand breaks
      and plays a critical role in the maintenance of genomic integrity. However,
      considering its role also in transcription, proliferation as well as apoptosis in
      biological process, in the present study the role of PARP in bone regeneration
      was evaluated, in particular in bone cell proliferation and differentiation
      processes. Thus, formalin fixed paraffin embedded specimens of 10 human bone
      samples after sinus lift were collected and investigated by immunohistochemistry
      using a mouse monoclonal anti-human PARP antibody. PARP was expressed in cells
      with morphological features of osteoblasts in the areas of new bone formation at
      the junction between mineralized and unmineralized tissue, between osteoid tissue
      and bone. Few osteoclasts were observed and showed only focal nuclear expression
      of PARP, while osteocytes showed no positivity for PARP. Our data showed an
      overall involvement of PARP enzyme in human bone tissues, in particular during
      bone regeneration process. 

PMID- 25620191
TI  - Impact of coronary artery stent edge dissections on long-term clinical outcome in
      patients with acute coronary syndrome: an optical coherence tomography study.
AB  - AIMS: The purpose of the present study was to assess the incidence, predictors
      and long term prognosis of stent edge dissections identified by (OCT) after the
      implantation of bare metal (BMS) and drug eluting stents (DES). METHODS AND
      RESULTS: We studied 74 patients who underwent percutaneous coronary intervention
      (PCI) because of an acute coronary syndrome. Edge dissections were found in 29 of
      74 patients (39.1%). Independent predictors of edge dissections were: the
      presence of ST-elevation myocardial infarction (STEMI) (P = 0.005, odds ratio
      11.78; 95% Cl 2.06-67.10), the small reference lumen diameter (P = 0.009, odds
      ratio 0.11; 95% Cl 0.02-0.58) and the short stents implanted (P = 0.013, odds
      ratio 0.83; 95% Cl 0.72-0.96). During a follow-up period of 25.6 +/- 9.4 months
      11 patients presented with at least one major adverse cardiac event. Event free
      survival was significantly decreased in patients with edge dissection with a flap
      thickness >0.31 mm compared to patients with thinner flap or without any
      dissection (P < 0.001). CONCLUSIONS: OCT frequently detects edge dissections,
      usually related to STEMI presentation and to PCI technique. Deep vessel wall
      injury at stent edges with a dissection flap thickness more than 0.31mm carries
      an adverse clinical impact on long-term clinical outcome.

PMID- 25620192
TI  - [Knee revision arthroplasty : cementless, metaphyseal fixation with sleeves].
AB  - OBJECTIVE: Primary and long-term fixation of cementless metaphyseal implants in
      knee revision arthroplasty cases with large bone defects. INDICATIONS: All tibial
      and femoral bone defects AORI grade 2 and 3. CONTRAINDICATIONS: Cases where
      stable uncemented fixation of the metaphyseal implant is not possible. SURGICAL
      TECHNIQUE: Pre-operative evaluation of the failure mode and implant fixation
      planning. After opening the joint, a synovectomy and mobilisation of medial and
      lateral recesses routinely performed. Testing of ligamentous stability and
      implant fixation undertaken before explantation. Removal of the bearing, femoral
      and tibial components with osteotomes or oscillating saw. Tibial diaphysis
      prepared with reamers, and metaphyseal preparation with broaches and stem
      extension. Placement of the metaphyseal broach for height with respect to the
      tibial joint line and rotational stability assessed. Tibial tray size and
      position determined before implanting the sleeve, stem and tray trial. The tibial
      trial provides a stable platform for analysis of the extension and flexion gaps
      with spacer blocks. Diaphyseal reamers used to identify the anterior femoral bow.
      Metaphyseal broaches used to achieve stable fixation up to the resection line
      marked on the handle. Distal femoral freshening cut in 5 degrees  or 7 degrees 
      of valgus made to accommodate distal augments as needed. Positioning of the 4-in
      1 block with reconstruction of the posterior off-set and cutting for posterior
      augmentation. Selection of a box cut corresponding to the amount of constraint
      needed. Trial insert with appropriate, stem, sleeve, condylar femur and augments
      introduced. Bearing size, joint stability and ROM assessed. Patella alignment and
      the need for patella replacement or revision determined. The definitive implants
      are cemented at the joint surface, with metaphyseal sleeves and diaphyseal stems
      are uncemented. POSTOPERATIVE MANAGEMENT: Full weight bearing as tolerated,
      physiotherapy, lymph drainage and pain therapy are routine with no specific post
      operative management required. RESULTS: Between 2007 and 2011, 193 sleeves (119
      tibial/74 femoral) were implanted in 121 aspetic knee revision arthroplasties.
      After average of 3.6 years they were analysed clinically and radiographically.
      The AKSS (American Knee Society Score) increased from 88 +/- 18 to 147 +/- 23
      points (p < 0.01). ROM (range of motion) increased from 89 +/- 6 degrees  to 114
      +/- 4 degrees . Overall revision rate was 11.6 %. Only 4 sleeves revised for
      aseptic loosening (2 % of total sleeves). An additional 10 revisions performed
      mainly for infection (3.3 %) or ligament instability (3.3 %).

PMID- 25620193
TI  - The rural-urban enigma of allergy: what can we learn from studies around the
      world?
AB  - Childhood asthma and related allergic conditions have become the most common
      chronic disorders in the Western world. Many studies from around the world have
      demonstrated an increasing trend of asthma prevalence over the last few decades
      (Lancet, 368, 2004, 733). A few recent reports also suggested that childhood
      asthma prevalence may be showing a plateau or even a decline in few developed
      countries. Given the rapid changes in the prevalence over a short period of time,
      environmental factors are the more likely candidates explaining such trend. One
      of the most consistent epidemiological findings was that subjects living in the
      rural areas had lower prevalence of allergies when compared to those from urban
      areas (Clin Exp Allergy 30, 2000, 187; Pediatr Pulmonol 44, 2009, 793). Clear
      understanding of the mechanisms of how the environmental determinants in the
      rural environment may affect the early immune system resulting in lower risk of
      allergies and asthma will facilitate the development of future primary preventive
      strategies. In this study, we review recent data from around the world and
      explore the epidemiology and mechanistic studies that may explain the rural-urban
      difference of allergies. 

PMID- 25620194
TI  - Base-promoted coupling of carbon dioxide, amines, and N-tosylhydrazones: a novel
      and versatile approach to carbamates.
AB  - A base-promoted three-component coupling of carbon dioxide, amines, and N
      tosylhydrazones has been developed. The reaction is suggested to proceed via a
      carbocation intermediate and constitutes an efficient and versatile approach for
      the synthesis of a wide range of organic carbamates. The advantages of this
      method include the use of readily available substrates, excellent functional
      group tolerance, wide substrate scope, and a facile work-up procedure. 

PMID- 25620195
TI  - Effects of Hyriopsis cumingii polysaccharides on angiogenesis, macrophage
      chemotaxis, proliferation and phagocytosis.
AB  - Anti-angiogenic activities of crude Hyriopsis cumingii polysaccharides (HCPS) and
      its purified fractions (HCPS-1, HCPS-2 and HCPS-3) were evaluated in vivo using
      the chicken embryo chorioallantoic membrane (CAM) assay. The promoting effects of
      crude HCPS and its purified fractions on the chemotaxis, proliferation and
      phagocytosis of peritoneal macrophage were tested by cell model in vitro and
      cyclophosphamide-induced immuno-suppression animal model in vivo. The results
      showed that HCPS could significantly suppress the neovascularization of chicken
      embryo CAM and promote peritoneal macrophage migrating to monocyte chemotactic
      protein-1 (MCP-1), propagating and devouring sheep red blood cell (SRBC) in a
      dose-dependent manner. In addition, HCPS-3 showed stronger immunostimulatory
      activities in vitro than crude HCPS, HCPS-1 and HCPS-2. The beneficial effects of
      HCPS on the immune system might be, at least in part, attributed to the
      improvement of chemotaxis, proliferation and phagocytosis of peritoneal
      macrophage. All these results suggest that HCPS is a potential immunoenhancing
      and anti-tumor agent. 

PMID- 25620196
TI  - Forced entrainment by using light therapy, modafinil and melatonin in a sighted
      patient with non-24-hour sleep-wake disorder.

PMID- 25620197
TI  - Dissociation of EEG and autonomic sleep physiology.

PMID- 25620198
TI  - Effect of below-the-knee compression stockings on severity of obstructive sleep
      apnea.
AB  - BACKGROUND: Overnight fluid shift from the legs to the neck may narrow the upper
      airway and contribute to obstructive sleep apnea (OSA) pathogenesis. We
      hypothesized that below-the-knee compression stockings will decrease OSA severity
      in a general OSA population by decreasing daytime leg fluid accumulation and
      overnight fluid shift and increasing upper-airway size. METHODS: Patients with
      OSA (apnea-hypopnea index >= 10) were randomized to wear compression stockings
      during the daytime or to a control group for 2 weeks. Overnight polysomnography
      with measurement of leg and neck fluid volumes and upper-airway cross-sectional
      area before and after sleep was performed at baseline and follow-up. The primary
      outcome was change in the apnea-hypopnea index. RESULTS: Twenty-two patients
      randomized to compression stockings and 23 to control completed the study. The
      apnea-hypopnea index decreased significantly more in the compression stockings
      than in the control group (from 32.4 +/- 20.0 to 23.8 +/- 15.5 vs. from 31.2 +/-
      25.0 to 30.3 +/- 23.8, p = 0.042), in association with a significantly greater
      reduction in the overnight decrease in leg fluid volume (p = 0.028), and a
      significantly greater increase in morning upper-airway cross-sectional area (p =
      0.006). Overnight change in neck fluid volume was unchanged. CONCLUSION: These
      observations suggest that in, a general OSA population, below-the-knee
      compression stockings decrease OSA severity modestly via attenuation of overnight
      fluid shift and consequent upper-airway dilatation.

PMID- 25620200
TI  - Longitudinal changes in insomnia status and incidence of physical, emotional, or
      mixed impairment in postmenopausal women participating in the Women's Health
      Initiative (WHI) study.
AB  - OBJECTIVES/BACKGROUND: We assessed prevalence and correlates of insomnia;
      associations between changes in insomnia with incidence of physical, emotional,
      and mixed impairments (PI, EI, and MI, respectively); and age as a moderator in
      these relationships. PARTICIPANTS/METHODS: The Women's Health Initiative (WHI)
      clinical trial (CT) and observational study (OS) cohorts with 1- and 3-year
      follow-ups, respectively, were studied. Participants included 39,864 CT and
      53,668 OS postmenopausal women free of PI or EI at baseline. Insomnia Rating
      Scale (IRS), with a cutoff score of >=9 indicated insomnia. Normal-Normal,
      Abnormal-Abnormal, Normal-Abnormal, and Abnormal-Normal categories indicated
      change in insomnia over time. PI, EI, and MI were constructed using Short Form-36
      (SF-36) Physical and Emotional subscales (cutoff <=60) and the modified Center
      for Epidemiological Studies Depression scale (cutoff <=0.06). RESULTS: Among
      93,532 women, 24.5% had insomnia at baseline. The highest odds ratios (ORs) for
      impairments were found in the Normal-Abnormal and Abnormal-Abnormal categories.
      In the CT cohort, Normal-Abnormal category, ORs were 1.86 (95% CI = 1.57-2.20)
      for PI, 4.11 (95% CI = 3.59-4.72) for EI, and 6.37 (95% CI = 4.65-8.74) for MI.
      Respective ORs for the OS cohort were 1.70 (95% CI = 1.51-1.89), 3.80 (95% CI =
      3.39-4.25), and 4.41 (95% CI = 3.56-5.46). Interactions between changes in
      insomnia and age showed distinct albeit nonsignificant patterns. CONCLUSIONS: The
      results suggest that exposure to insomnia increases vulnerability to impairment.
      Future studies are needed to understand the directionality of these
      relationships.

PMID- 25620199
TI  - Phase advancing human circadian rhythms with morning bright light, afternoon
      melatonin, and gradually shifted sleep: can we reduce morning bright-light
      duration?
AB  - OBJECTIVE: Efficient treatments to phase-advance human circadian rhythms are
      needed to attenuate circadian misalignment and the associated negative health
      outcomes that accompany early-morning shift work, early school start times, jet
      lag, and delayed sleep phase disorder. This study compared three morning bright
      light exposure patterns from a single light box (to mimic home treatment) in
      combination with afternoon melatonin. METHODS: Fifty adults (27 males) aged 25.9
      +/- 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment
      days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on
      treatment day 1, and an hour earlier each treatment day. They were exposed to one
      of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min
      exposures separated by 30 min of room light (2-h group), four 15-min exposures
      separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h
      group). Dim-light melatonin onsets (DLMOs) before and after treatment determined
      the phase advance. RESULTS: Compared to the 2-h group (phase shift = 2.4 +/- 0.8
      h), smaller phase-advance shifts were seen in the 1-h (1.7 +/- 0.7 h) and 0.5-h
      (1.8 +/- 0.8 h) groups. The 2-h pattern produced the largest phase advance;
      however, the single 30-min bright-light exposure was as effective as 1 h of
      bright light spread over 3.25 h, and it produced 75% of the phase shift observed
      with 2 h of bright light. CONCLUSIONS: A 30-min morning bright-light exposure
      with afternoon melatonin is an efficient treatment to phase-advance human
      circadian rhythms.

PMID- 25620201
TI  - (-)-epigallocatechin-3-gallate inhibits fibrillogenesis of chicken cystatin.
AB  - Previous studies have reported that (-)-epigallocatechin-3-gallate (EGCG), the
      most abundant flavonoid in green tea, can bind to unfolded native polypeptides
      and prevent conversion to amyloid fibrils. To elucidate whether this antifibril
      activity is specific to disease-related target proteins or is more generic, we
      investigated the ability of EGCG to inhibit amyloid fibril formation of
      amyloidogenic mutant chicken cystatin I66Q, a generic amyloid-forming model
      protein that undergoes fibril formation through a domain swapping mechanism. We
      demonstrated that EGCG was a potent inhibitor of amyloidogenic cystatin I66Q
      amyloid fibril formation in vitro. Computational analysis suggested that EGCG
      prevented amyloidogenic cystatin fibril formation by stabilizing the molecule in
      its native-like state as opposed to redirecting aggregation toward disordered and
      amorphous aggregates. Therefore, although EGCG appears to be a generic inhibitor
      of amyloid-fibril formation, the mechanism by which it achieves such inhibition
      may be specific to the target fibril-forming polypeptide.

PMID- 25620202
TI  - Self-cleaning properties in engineered sensors for dopamine electroanalytical
      detection.
AB  - Fouling and passivation are the major drawbacks for a wide applicability of
      electroanalytical sensors based on nanomaterials, especially in biomedical and
      environmental fields. The production of highly engineered devices, designed ad
      hoc for specific applications, is the key factor in the direction of overcoming
      the problem and accessing effective sensors. Here, the fine-tuning of the system,
      composed of a highly ordered distribution of silver nanoparticles between a
      bottom silica and a top titania layer, confers multifunctional properties to the
      device for a biomedical complex challenge: dopamine detection. The crucial
      importance of each component towards a robust and efficient electroanalytical
      system is studied. The total recovery of the electrode performance after a simple
      UV-A cleaning step (self-cleaning), due to the photoactive interface and the
      aging resistance, is deeply investigated. 

PMID- 25620203
TI  - Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten
      syndrome.
AB  - Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder
      characterized by dental dysplasia, aortic calcification, skeletal abnormalities,
      glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant
      pattern of inheritance, the genetic background of SMS and information about its
      phenotypic heterogeneity remain unknown. Recently, we found a family affected by
      glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with
      classic SMS, affected individuals showed normal dentition, suggesting atypical
      SMS. To identify genetic causes of the disease, we performed exome sequencing in
      this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose
      protein product is also known as RIG-I. Further analysis of DDX58 in 100
      individuals with congenital glaucoma identified another variant (c.803G>T
      [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic
      calcification but who suffered from glaucoma and skeletal abnormalities. Cys268
      and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively,
      and these residues are predicted to be located closer to the ADP and RNA
      molecules than other nonpathogenic missense variants by protein structure
      analysis. Functional assays revealed that DDX58 alterations confer constitutive
      activation and thus lead to increased interferon (IFN) activity and IFN
      stimulated gene expression. In addition, when we transduced primary human
      trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala)
      mutants, cytopathic effects and a significant decrease in cell number were
      observed. Taken together, our results demonstrate that DDX58 mutations cause
      atypical SMS manifesting with variable expression of glaucoma, aortic
      calcification, and skeletal abnormalities without dental anomalies. 

PMID- 25620204
TI  - A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome.
AB  - Singleton-Merten syndrome (SMS) is an infrequently described autosomal-dominant
      disorder characterized by early and extreme aortic and valvular calcification,
      dental anomalies (early-onset periodontitis and root resorption), osteopenia, and
      acro-osteolysis. To determine the molecular etiology of this disease, we
      performed whole-exome sequencing and targeted Sanger sequencing. We identified a
      common missense mutation, c.2465G>A (p.Arg822Gln), in interferon induced with
      helicase C domain 1 (IFIH1, encoding melanoma differentiation-associated protein
      5 [MDA5]) in four SMS subjects from two families and a simplex case. IFIH1 has
      been linked to a number of autoimmune disorders, including Aicardi-Goutieres
      syndrome. Immunohistochemistry demonstrated the localization of MDA5 in all
      affected target tissues. In vitro functional analysis revealed that the IFIH1
      c.2465G>A mutation enhanced MDA5 function in interferon beta induction.
      Interferon signature genes were upregulated in SMS individuals' blood and dental
      cells. Our data identify a gain-of-function IFIH1 mutation as causing SMS and
      leading to early arterial calcification and dental inflammation and resorption. 

PMID- 25620205
TI  - TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy
      specifically disturb several steps during transcription.
AB  - Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD
      A) subunits of the transcription and DNA-repair factor TFIIH lead to three
      autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with
      Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases
      were originally associated with defects in DNA repair, transcription deficiencies
      might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2)
      as a model in several cells bearing mutations in genes encoding TFIIH subunits,
      we observed that (1) the recruitment of the TFIIH complex was altered at the
      activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide
      excision repair (NER) factors during transcription in a manner different from
      that observed during NER, and (3) the different TFIIH variants disturbed
      transcription by having distinct consequences on post-translational modifications
      of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The
      transition from heterochromatin to euchromatin was disrupted depending on the
      variant, illustrating the fact that TFIIH, by contributing to NER factor
      recruitment, orchestrates chromatin remodeling. The subtle transcriptional
      differences found between various TFIIH variants thus participate in the
      phenotypic variability observed among XP, XP/CS, and TTD individuals. 

PMID- 25620206
TI  - Estimates of continental ancestry vary widely among individuals with the same
      mtDNA haplogroup.
AB  - The association between a geographical region and an mtDNA haplogroup(s) has
      provided the basis for using mtDNA haplogroups to infer an individual's place of
      origin and genetic ancestry. Although it is well known that ancestry inferences
      using mtDNA haplogroups and those using genome-wide markers are frequently
      discrepant, little empirical information exists on the magnitude and scope of
      such discrepancies between multiple mtDNA haplogroups and worldwide populations.
      We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to
      those made by autosomal SNPs in ~940 samples of the Human Genome Diversity Panel
      and recently admixed populations from the 1000 Genomes Project. Continental
      ancestry proportions often varied widely among individuals sharing the same mtDNA
      haplogroup. For only half of mtDNA haplogroups did the highest average
      continental-ancestry proportion match the highest continental-ancestry proportion
      of a majority of individuals with that haplogroup. Prediction of an individual's
      mtDNA haplogroup from his or her continental-ancestry proportions was often
      incorrect. Collectively, these results indicate that for most individuals in the
      worldwide populations sampled, mtDNA-haplogroup membership provides limited
      information about either continental ancestry or continental region of origin. 

PMID- 25620207
TI  - Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying K+
      channel encoded by KCNJ6.
AB  - Keppen-Lubinsky syndrome (KPLBS) is a rare disease mainly characterized by severe
      developmental delay and intellectual disability, microcephaly, large prominent
      eyes, a narrow nasal bridge, a tented upper lip, a high palate, an open mouth,
      tightly adherent skin, an aged appearance, and severe generalized lipodystrophy.
      We sequenced the exomes of three unrelated individuals affected by KPLBS and
      found de novo heterozygous mutations in KCNJ6 (GIRK2), which encodes an inwardly
      rectifying potassium channel and maps to the Down syndrome critical region
      between DIRK1A and DSCR4. In particular, two individuals shared an in-frame
      heterozygous deletion of three nucleotides (c.455_457del) leading to the loss of
      one amino acid (p.Thr152del). The third individual was heterozygous for a
      missense mutation (c.460G>A) which introduces an amino acid change from glycine
      to serine (p.Gly154Ser). In agreement with animal models, the present data
      suggest that these mutations severely impair the correct functioning of this
      potassium channel. Overall, these results establish KPLBS as a channelopathy and
      suggest that KCNJ6 (GIRK2) could also be a candidate gene for other
      lipodystrophies. We hope that these results will prompt investigations in this
      unexplored class of inwardly rectifying K(+) channels. 

PMID- 25620208
TI  - "Look who's talking!" Gaze Patterns for Implicit and Explicit Audio-Visual Speech
      Synchrony Detection in Children With High-Functioning Autism.
AB  - Conversation requires integration of information from faces and voices to fully
      understand the speaker's message. To detect auditory-visual asynchrony of speech,
      listeners must integrate visual movements of the face, particularly the mouth,
      with auditory speech information. Individuals with autism spectrum disorder may
      be less successful at such multisensory integration, despite their demonstrated
      preference for looking at the mouth region of a speaker. We showed participants
      (individuals with and without high-functioning autism (HFA) aged 8-19) a split
      screen video of two identical individuals speaking side by side. Only one of the
      speakers was in synchrony with the corresponding audio track and synchrony
      switched between the two speakers every few seconds. Participants were asked to
      watch the video without further instructions (implicit condition) or to
      specifically watch the in-synch speaker (explicit condition). We recorded which
      part of the screen and face their eyes targeted. Both groups looked at the in
      synch video significantly more with explicit instructions. However, participants
      with HFA looked at the in-synch video less than typically developing (TD) peers
      and did not increase their gaze time as much as TD participants in the explicit
      task. Importantly, the HFA group looked significantly less at the mouth than
      their TD peers, and significantly more at non-face regions of the image. There
      were no between-group differences for eye-directed gaze. Overall, individuals
      with HFA spend less time looking at the crucially important mouth region of the
      face during auditory-visual speech integration, which is maladaptive gaze
      behavior for this type of task.

PMID- 25620209
TI  - Embryonic stem cell differentiation requires full length Chd1.
AB  - The modulation of chromatin dynamics by ATP-dependent chromatin remodeling
      factors has been recognized as an important mechanism to regulate the balancing
      of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have
      studied the effects of a partial deletion of the gene encoding the chromatin
      remodeling factor Chd1 that generates an N-terminally truncated version of Chd1
      in mouse ESCs in vitro as well as in vivo. We found that a previously
      uncharacterized serine-rich region (SRR) at the N-terminus is not required for
      chromatin assembly activity of Chd1 but that it is subject to phosphorylation.
      Expression of Chd1 lacking this region in ESCs resulted in aberrant
      differentiation properties of these cells. The self-renewal capacity and ESC
      chromatin structure, however, were not affected. Notably, we found that newly
      established ESCs derived from Chd1(Delta2/Delta2) mutant mice exhibited similar
      differentiation defects as in vitro generated mutant ESCs, even though the N
      terminal truncation of Chd1 was fully compatible with embryogenesis and post
      natal life in the mouse. These results underscore the importance of Chd1 for the
      regulation of pluripotency in ESCs and provide evidence for a hitherto
      unrecognized critical role of the phosphorylated N-terminal SRR for full
      functionality of Chd1. 

PMID- 25620210
TI  - LC/ESI-MS/MS method for determination of salivary eicosapentaenoic acid
      concentration to arachidonic acid concentration ratio.
AB  - A simple liquid chromatography/electrospray ionization-tandem mass spectrometry
      (LC/ESI-MS/MS) method for determination of the eicosapentaenoic acid (EPA)
      concentration to arachidonic acid (AA) concentration ratio in human saliva has
      been developed. The EPA/AA ratio in serum or plasma is widely recognized as a
      useful indicator in identifying the risk of cardiovascular disease, especially
      atherosclerosis. The salivary EPA/AA ratio is expected to be a convenient
      alternative to the serum or plasma EPA/AA ratio, because saliva offers the
      advantages of easy and noninvasive sampling. The saliva was deproteinized with
      acetonitrile, purified using an Oasis HLB cartridge, and derivatized with 1-[(4
      dimethylaminophenyl)carbonyl]piperazine (DAPPZ). The derivatized EPA and AA were
      subjected to LC/ESI-MS/MS, and the EPA/AA ratio was determined using the selected
      reaction monitoring mode. The DAPPZ-derivatization increased the ESI sensitivity
      by 100- and 300-fold for EPA and AA, respectively, and enabled the detection of
      trace fatty acids in saliva using a 200 MUL sample. The assay reproducibility was
      satisfactory (relative standard deviation, <5.0%). The method was successfully
      applied to the measurement of the salivary EPA/AA ratios of healthy Japanese
      subjects and their changes owing to the supplementation of EPA.

PMID- 25620211
TI  - Study for Promotion of Health in Recycling Lead - Rationale and design.
AB  - BACKGROUND: The level at which low-level lead exposure produces subclinical
      adverse health effects in adults remains to be established. METHODS: The Study
      for Promotion of Health in Recycling Lead (SPHERL) will enroll 500 newly hired
      workers, whose blood lead during 2 years of follow-up is expected to increase
      from levels less than 2 MUg/dl, as currently observed in the US population, to 20
      30 MUg/dl. The main outcome variables to be studied are (i) blood pressure (BP)
      analyzed as a continuous or categorical variable, both cross-sectionally and
      longitudinally, and using conventional and ambulatory BP measurement; (ii)
      indexes of glomerular and tubular renal function, (iii) heart rate variability
      analyzed in the frequency domain as measure of autonomous sympathetic modulation,
      (iv) peripheral nerve conductivity velocity, (v) neurocognitive performance, and
      (vi) quality of life. Expected outcomes. Assuming a 10-fold increase in blood
      lead, SPHERL will have sufficient statistical power to detect over 2 years a
      steepening of the age-related rise in systolic BP from 1 to 5 mmHg and a doubling
      of the age-related decline in the estimated glomerular filtration rate from 3.5
      to 7.0 ml/min/1.73 m(2). The longitudinal design of our study complies with the
      temporality principle of the Bradford-Hill criteria for assessing possible
      causality between outcomes and exposure. SPHERL will attempt to resolve the
      apparent contradiction between general population studies showing associations
      between adverse health effects and low lead exposure with blood lead levels below
      5 MUg/dl and studies conducted in occupational cohorts indicating that adverse
      effects of lead exposure occur at much higher blood lead levels.

PMID- 25620212
TI  - Radiation treatment and cancer stem cells.
AB  - Radiotherapy is a standard treatment for many cancers and is frequently used as
      primary or adjuvant therapy, often in combination with surgery or chemotherapy or
      both. However, locoregional recurrence or metastatic spread still occurs in a
      high proportion of patients after radiotherapy. In this regard, emerging
      evidences suggest that sublethal radiation paradoxically promotes expansion of
      cancer stem cell population that is highly tumorigenic and is reminiscent of non
      neoplasm stem cells. In this review, we discussed recent findings that
      demonstrate the increase in cancer stem cells after irradiation, and the possible
      cellular mechanisms with a perspective of tumor microenvironment. A further
      understating on the mechanistic mechanisms underlying radiation-enhanced
      malignant phenotypes might increase the efficacy of radiotherapy for cancer
      treatment.

PMID- 25620213
TI  - Jordan M. Philips keynote speaker: uterine transplantation.

PMID- 25620214
TI  - Spontaneous Uroperitoneum and Preterm Delivery in a Patient With Bladder
      Endometriosis.

PMID- 25620215
TI  - Peritoneal closure over barbed suture to prevent adhesions: a randomized
      controlled trial in an animal model.
AB  - STUDY OBJECTIVE: To compare adhesion formation and histological features of
      peritoneal closure and nonclosure over an intra-abdominally placed barbed suture.
      DESIGN: Single-blind randomized controlled trial (Canadian Task Force
      Classification I). SETTING: Certified animal research facility. SUBJECTS: Eight
      nonpregnant rats. INTERVENTIONS: Abdominal cavities were entered via midline
      incision. Left and right parietal peritoneal surfaces were incised 1.5 cm long
      separately and stitched with unidirectional barbed suture material (3/0 V-Loc).
      The parietal peritoneum was approximated over the barbed suture using
      polypropylene suture material (7/0 Prolene) to embed the barbed suture
      (peritonization) on one side, and left open on the other side. The side of the
      barbed suture to be peritonized was allocated at random. On the postoperative day
      32, all rats were sacrificed, adhesion formations on each side were
      macroscopically scored, and histological features were evaluated microscopically.
      MEASUREMENT AND MAIN RESULTS: The median adhesion score was 2.00 (range, 1-4) on
      operative fields. There was no statistically significant difference in median
      adhesion score between the peritonized and nonperitonized sides (1.5 vs 2,
      respectively; p = .13). Microscopically, there were no statistically significant
      differences in median acute and chronic inflammation scores between the
      peritonized and nonperitonized sides (p = .58 and p = .45, respectively), but a
      significantly higher median fibrosis score on the peritonized side (3 vs 1.5,
      respectively; p = .02). CONCLUSION: Based on the results of the present study in
      a rat model, barbed suture material might be associated with adhesion formation
      when used intra-abdominally, and these adhesions could not be prevented by
      peritonization.

PMID- 25620216
TI  - Laparoscopic excisional surgery for growing teratoma syndrome of the ovary: case
      report and literature review.
AB  - Growing teratoma syndrome (GTS) is rare clinical phenomenon occurring as a
      sequelae of a malignant germ cell tumor. We present the case of a 20-year-old
      woman who developed GTS after undergoing fertility-sparing surgery and
      chemotherapy for an immature teratoma. She underwent left salpingo-oophorectomy,
      right ovarian cystectomy, and disseminated tumor reduction during her primary
      surgery. The postsurgical histology report identified the tumor as an immature
      teratoma, grade 3, International Federation of Gynecology and Obstetrics (FIGO)
      stage IIIb. She subsequently received 3 cycles of chemotherapy consisting of
      bleomycin, etoposide, and cisplatin. At 17 months after the chemotherapy, follow
      up computed tomography (CT) scan revealed an enlarged mass in her right paracolic
      gutter and a small peritoneal lesion in the pouch of Douglas. Her serum alpha
      fetoprotein level was not elevated. These findings were compatible with GTS, but
      it was difficult to rule out a recurrent immature teratoma. Diagnostic
      exploratory laparoscopic surgery revealed the enlarged tumors that had been
      detected by the CT scan. Although there were multiple tumors in the pouch of
      Douglas, we were able to resect all of them laparoscopically. Histological
      diagnosis of the surgically resected specimens was of a mature teratoma, and so
      we concluded that this tumor was a GTS. Our experience suggests that laparoscopic
      surgery is an effective alternative diagnostic and therapeutic approach in cases
      suspicious of GTS where the disease is disseminated to the peritoneum. 

PMID- 25620217
TI  - Effect of second-look laparoscopy on subsequent fertility outcome after
      laparoscopic salpingostomy for tubal pregnancy: a randomized controlled study.
AB  - OBJECTIVE: To clarify the potential value of second-look laparoscopy (SLL) in
      improving fertility outcomes after laparoscopic salpingostomy for tubal
      pregnancy. DESIGN: Randomized controlled trial. SETTING: West China Second
      University Hospital, Sichuan University. PATIENTS: 216 women with future birth
      demand who underwent laparoscopic salpingostomy for tubal pregnancy.
      INTERVENTIONS: SLL was performed in the SLL group at 3 months after the primary
      surgery. MEASUREMENT AND MAIN RESULTS: In both the SLL and control groups, the
      subjects were assigned to a slight adhesion (SLA) or severe adhesion (SEA)
      subgroup. At 3-year follow-up, the fertility outcomes were compared between the
      SLL and control groups and also between the SLA and SEA subgroups. The
      intrauterine pregnancy rate was higher in the SLL group compared with the control
      group (63.1% vs 48.6%; p = .032), and the incidence of recurrent ectopic
      pregnancy was lower in the SLL group than in the control group (6.3% vs 16.2%; p
      = .021). In the control group, the cumulative pregnancy rate was higher in the
      SLA subgroup compared with the SEA subgroup (p = .017), but in the SLL group, the
      cumulative pregnancy rate did not differ between the 2 subgroups (p = .502). The
      cumulative pregnancy rate was higher in the SEA subgroup of the SLL group
      compared with the SEA subgroup of the control group (p = .014), but did not
      differ between the SLA subgroup of the SLL group and the SLA subgroup of the
      control group (p = .456). CONCLUSION: SLL may improve subsequent fertility
      outcome after laparoscopic salpingostomy for tubal pregnancy, and may be
      especially recommended for women with severe and extensive pelvic adhesions.

PMID- 25620218
TI  - Quantitative assessment of liver fibrosis by digital image analysis: Relationship
      to Ishak staging and elasticity by shear-wave elastography.
AB  - OBJECTIVE: To analyze the relationship between fibrosis staged by Ishak stage and
      quantified by digital image analysis (DIA), and to reveal the optimum performance
      of shear-wave elastography (SWE) using quantitative DIA measurements as a
      comparative histological standard. METHODS: The proportionate area (PA) of
      fibrosis was measured by DIA from images of the PA of trichrome-stain (TPA) of
      168 chronic hepatitis patients. SWE was performed in 105 patients. The accuracy
      of SWE for predicting the fibrosis defined by quantitative PA thresholds (>=
      2.5%, >= 5%, >= 10% and >= 20%, respectively) and by Ishak stages was measured
      using the area under the receiver operating characteristic curve (AUROC).
      RESULTS: DIA was proven to be highly reproducible (interclass correlation
      coefficient  0.926). The TPA range corresponding to each Ishak stage was large,
      widened as stages progressed, and reached its greatest extent in cirrhosis. TPA
      magnified at *50 ranges 11.9-56% for Ishak stage F5-6. A good correlation between
      TPA and elasticity was presented for more advanced fibrosis (TPA >=10%, rs  =
      0.732, P = 0.000) than milder fibrosis (TPA <10%, rs  = 0.308, P = 0.006). With
      the advance of fibrosis either by stages or PA thresholds the discriminative
      accuracy of SWE gradually increased, but was less satisfactory for milder
      fibrosis. CONCLUSIONS: DIA may serve as a reproducible and reliable quantitative
      standard for surrogate tests for liver fibrosis. The performance and correlation
      of SWE with the fibrotic extent were better for advanced fibrosis, but less
      satisfactory for milder fibrosis.

PMID- 25620219
TI  - Workplace interventions for reducing sitting at work.
AB  - BACKGROUND: The number of people working whilst seated at a desk keeps increasing
      worldwide. As sitting increases, occupational physical strain declines at the
      same time. This has contributed to increases in cardiovascular disease, obesity
      and diabetes. Therefore, reducing and breaking up the time that people spend
      sitting while at work is important for health. OBJECTIVES: To evaluate the
      effects of workplace interventions to reduce sitting at work compared to no
      intervention or alternative interventions. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      CINAHL, OSH UPDATE, PsycINFO, Clinical trials.gov and the World Health
      Organization (WHO) search trial portal up to 14 February, 2014. We also searched
      reference lists of articles and contacted authors. SELECTION CRITERIA: We
      included randomised controlled trials (RCT), cluster-randomised controlled trials
      (cRCTs), and quasi-randomised controlled trials of interventions to reduce
      sitting at work. For changes of workplace arrangements, we also included
      controlled before-and-after studies (CBAs) with a concurrent control group. The
      primary outcome was time spent sitting at work per day, either self-reported or
      objectively measured by means of an accelerometer coupled with an inclinometer.
      We considered energy expenditure, duration and number of sitting episodes lasting
      30 minutes or more, work productivity and adverse events as secondary outcomes.
      DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles,
      abstracts and full-text articles for study eligibility. Two review authors
      independently extracted data and assessed risk of bias. We contacted authors for
      additional data where required. MAIN RESULTS: We included eight studies, four
      RCTs, three CBAs and one cRCT, with a total of 1125 participants. The studies
      evaluated physical workplace changes (three studies), policy changes (one study)
      and information and counselling (four studies). No studies investigated the
      effect of treadmill desks, stepping devices, periodic breaks or standing or
      walking meetings. All the studies were at high risk of bias. The quality of the
      evidence was very low to low. Half of the studies were from Australia and the
      other half from Europe, with none from low- or middle-income countries. Physical
      workplace changesWe found very low quality evidence that sit-stand desks with or
      without additional counselling reduced sitting time at work per workday at one
      week follow-up (MD -143 minutes (95% CI -184 to -102, one study, 31 participants)
      and at three months' follow-up (MD - 113 minutes, 95% CI -143 to -84, two
      studies, 61 participants) compared to no intervention. Total sitting time during
      the whole day decreased also with sit-stand desks compared to no intervention (MD
      -78 minutes, 95% CI -125 to -30, one study, 31 participants) as did the duration
      of sitting episodes lasting 30 minutes or more (MD -52 minutes, 95% CI -79 to 
      26, two studies, 74 participants). Sit-stand desks did not have a considerable
      effect on work performance and had an inconsistent effect on musculoskeletal
      symptoms and sick leave. Policy changesWalking strategies had no considerable
      effect on sitting at work (MD -16 minutes, 95% CI -54 to 23, one study, 179
      participants, low quality evidence). Information and counsellingGuideline-based
      counselling by occupational physicians reduced sitting time at work (MD -28
      minutes, 95% CI -54 to -2, one study, 396 participants, low quality evidence).
      There was no considerable effect on reduction in total sitting time during the
      whole day.Mindfulness training induced a non-significant reduction in workplace
      sitting time (MD -2 minutes, 95% CI -22 to 18) at six months' follow-up and at 12
      months' follow-up (MD -16 minutes, 95% CI -45 to 12, one study, 257 participants,
      low quality evidence).There was an inconsistent effect of computer prompting on
      sitting time at work. One study found no considerable effect on sitting at work
      (MD -18 minutes, 95% CI -53 to 17, 28 participants, low quality evidence) at 10
      days' follow-up, while another study reported a significant reduction in sitting
      at work (MD -55 minutes, 95% CI -96 to -14, 34 participants, low quality
      evidence) at 13 weeks' follow-up. Computer prompting software also led to a non
      significant increase in energy expenditure at work (MD 278 calories/workday, 95%
      CI 0 to 556, one study, 34 participants, low quality evidence) at 13 weeks'
      follow-up. AUTHORS' CONCLUSIONS: At present there is very low quality evidence
      that sit-stand desks can reduce sitting time at work, but the effects of policy
      changes and information and counselling are inconsistent. There is a need for
      high quality cluster-randomised trials to assess the effects of different types
      of interventions on objectively measured sitting time. There are many ongoing
      trials that might change these conclusions in the near future.

PMID- 25620220
TI  - Dinuclear ruthenium(II) complexes that induce and stabilise G-quadruplex DNA.
AB  - A series of dinuclear ruthenium(II) complexes were synthesised, and the complexes
      were determined to be new highly selective compounds for binding to telomeric G
      quadruplex DNA. The interactions of these complexes with telomeric G-quadruplex
      DNA were studied by using circular dichroism (CD) spectroscopy, fluorescence
      resonance energy transfer (FRET) melting assays, isothermal titration calorimetry
      (ITC) and molecular modelling. The results showed that the complexes 1, 2 and 4
      induced and stabilised the formation of antiparallel G-quadruplexes of telomeric
      DNA in the absence of salt or in the presence of 100 mM K(+)-containing buffer.
      Furthermore, complexes 1 and 2 strongly bind to and effectively stabilise the
      telomeric G-quadruplex structure and have significant selectivity for G
      quadruplex over duplex DNA. In comparison, complex 3 had a much lesser effect on
      the G-quadruplex, suggesting that possession of a suitably sized plane for good
      pi-pi stacking with the G-quadruplets is essential for the interaction of the
      dinuclear ruthenium(II) complexes with the G-quadruplex. Moreover, telomerase
      inhibition by the four complexes and their cellular effects were studied, and
      complex 1 was determined to be the most promising inhibitor of both telomerase
      and HeLa cell proliferation.

PMID- 25620221
TI  - From microbiology to cancer biology: the Rid protein family prevents cellular
      damage caused by endogenously generated reactive nitrogen species.
AB  - The Rid family of proteins is highly conserved and broadly distributed throughout
      the domains of life. Genetic and biochemical studies, primarily in Salmonella
      enterica, have defined a role for RidA in responding to endogenously generated
      reactive metabolites. The data show that 2-aminoacrylate (2AA), a reactive
      enamine intermediate generated by some pyridoxal 5'-phosphate-dependent enzymes,
      accumulates in the absence of RidA. The accumulation of 2AA leads to covalent
      modification and inactivation of several enzymes involved in essential metabolic
      processes. This review describes the 2AA hydrolyzing activity of RidA and the
      effect of this biochemical activity on the metabolic network, which impacts
      organism fitness. The reported activity of RidA and the consequences encountered
      in vivo when RidA is absent have challenged fundamental assumptions in
      enzymology, biochemistry and cell metabolism regarding the fate of transiently
      generated reactive enamine intermediates. The current understanding of RidA in
      Salmonella and the broad distribution of Rid family proteins provide exciting
      opportunities for future studies to define metabolic roles of Rid family members
      from microbes to man. 

PMID- 25620222
TI  - Biomarkers of brevetoxin exposure and composite toxin levels in hard clam
      (Mercenaria sp.) exposed to Karenia brevis blooms.
AB  - Brevetoxins in clams (Mercenaria sp.) exposed to recurring blooms of Karenia
      brevis in Sarasota Bay, FL, were studied over a three-year period. Brevetoxin
      profiles in toxic clams were generated by ELISA and LC-MS. Several brevetoxin
      metabolites, as identified by LC-MS, were major contributors to the composite
      brevetoxin response of ELISA. These were S-desoxyBTX-B2 (m/z 1018), BTX-B2 (m/z
      1034), BTX-B5 (m/z 911), open A-ring BTX-B5 (m/z 929), and BTX-B1 (m/z 1018).
      Summed values of these metabolites were highly correlated (R(2) = 0.9) with
      composite B-type brevetoxin measurements by ELISA. S-desoxyBTX-B2, BTX-B2, and
      BTX-B1 were the most persistent and detectable in shellfish for several months
      after dissipation of blooms. These metabolites were selected as LC-MS biomarkers
      of brevetoxin exposure and reflective of composite B-type brevetoxins in hard
      clam. ELISA and LC-MS values were moderately correlated with toxicity of the
      shellfish by mouse bioassay. ELISA and LC-MS methods offer rapid screening and
      confirmatory determination of brevetoxins, respectively, as well as toxicity
      assessment in clams exposed to K. brevis blooms. 

PMID- 25620223
TI  - Metabolic cooperation in testis as a pharmacological target: from disease to
      contraception.
AB  - The development of a "male pill" to control fertility is still a major challenge.
      Although women have several options to play an active role in the couple family
      planning, men are very limited in terms of contraceptive methods. Several
      approaches have been proposed to develop a male contraceptive and can be divided
      in two major groups: hormonal and non-hormonal methods. Within the testis, the
      somatic Sertoli cell (SC) is known as the "nurse cell" since it provides the
      physical and nutritional support for the developing germ cells. Moreover,
      adjacent SCs form the Sertoli/blood testis barrier (BTB), which divides the
      seminiferous epithelium into the basal and the apical compartments, controlling
      the passage of substances to the site where germ cells develop. Among the several
      functions of SC, its metabolism and the production of lactate, acetate and other
      metabolic factors are essential for the normal occurrence of spermatogenesis. In
      the last years, several works have highlighted that the metabolic cooperation
      established between SCs and developing germ cells is compromised in several
      diseases associated with male subfertility/infertility. Notably, several
      metabolismassociated proteins are specifically expressed in the testis. Thus,
      there are several evidences illustrating that the control of male fertility can
      be achieved by targeting testicular cells metabolism. Herein, we discuss the
      metabolic cooperation in testis as a potential pharmacological target to
      counteract subfertility/infertility promoted by several diseases, particularly
      metabolic diseases. We also discuss how it can contribute to the development of a
      male contraceptive. 

PMID- 25620225
TI  - Phosphoprotein phosphatase 1 complexes in spermatogenesis.
AB  - The major post-translational modification in eukaryotes is protein
      phosphorylation which mediates responses to signals in a myriad of cellular
      processes. Not surprisingly, many steps in spermatogenesis involve the concerted
      action of the protein (de)phosphorylation key players, kinases and phosphatases.
      Phosphoprotein phosphatase 1 catalytic subunit (PPP1C), an evolutionarily
      conserved Ser/Thr-protein phosphatase, catalyzes the majority of eukaryotic
      protein dephosphorylation reactions. Three genes, PPP1CA, PPP1CB and PPP1CC,
      encode four PPP1C isoforms, PPP1CA, PPP1CB, PPP1CC1, and PPP1CC2. After
      transcription, PPP1CC undergoes tissue-specific splicing, originating a
      ubiquitously expressed isoform, PPP1CC1 and a testis-enriched and sperm-specific
      isoform, PPP1CC2 which is essential for completion of spermatogenesis. Highly
      similar PPP1C isoforms - PPP1CA and PPP1CB - are capable of compensating the loss
      of Ppp1cc in every tissue except in testis. PPP1C cellular functions depend on
      the complexes it forms with PPP1C Interacting Proteins (PIPs), which together
      with the different catalytic subunits, account for PPP1C specificity. This review
      will focus on the role of the major serine/threonine phosphatase - PPP1C and its
      holoenzymes in spermatogenesis. Furthermore, current challenges on the protein
      phosphatases field as targets to male contraception will be addressed. 

PMID- 25620224
TI  - Interaction of oligomeric breast cancer resistant protein (BCRP) with adjudin: a
      male contraceptive with anti-cancer activity.
AB  - Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC)
      transporter, which together with two other ABC efflux drug pumps, namely P
      glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1,
      ABCC1) is the most important multidrug resistance protein foun d in eukaryotic
      cells including cells in the testis. However, unlike P-gp and MRP1, which are
      components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed
      at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular
      myoid cells and endothelial cells of the lymphatic vessel in the tunica propria,
      residing outside the BTB. As such, the testis is equipped with two levels of
      defense against xenobiotics or drugs, preventing these harmful substances from
      entering the adluminal compartment to perturb meiosis and post-meiotic spermatid
      development: one at the level of the BTB conferred by P-gp and MRP1 and one at
      the tunica propria conferred by BCRP. The presence of drug transporters at the
      tunica propria as well as at the Sertoli cell BTB thus poses significant
      obstacles in developing non-hormonal contraceptives if these drugs (e.g.,
      adjudin) exert their effects in germ cells behind the BTB, such as in the
      adluminal (apical) compartment of the seminiferous epithelium. Herein, we
      summarize recent findings pertinent to adjudin, a non-hormonal male
      contraceptive, and molecular interactions of adjudin with BCRP so that this
      information can be helpful to devise delivery strategies to evade BCRP in the
      tunica propria to improve its bioavailability in the testis. 

PMID- 25620226
TI  - Targeting post-ejaculation sperm for value-added contraception.
AB  - The spermatogenesis is a precisely-timed cellular proliferation that takes place
      in the seminiferous tubules of testes and is meticulously regulated by
      gonadotrophins, androgens and temperature. Hormonal, nonhormonal and thermal
      methods of male contraception have been researched with success; though a
      clinically viable method is yet to evolve. Testicular sperm lack motility and
      fertilizing ability, which they gain during their transit through the long
      epididymal conduit whose distal end serves as a store house of mature sperm in a
      quiescent state, ready for ejaculation during coitus. Epididymal maturation has
      been a target for male contraceptive research to avert interruptions of
      fundamental testicular functions like spermatogenesis and steroidogenesis.
      However, several experimental successes have not yet yielded a practicable method
      of fertility regulation. Coitus culminates in the propulsion of epididymal sperm
      within seconds through the vas deferens into the female vagina and marks the
      initiation of sperm motility, a vigorous physical activity that is crucial for
      fertilization. Highly motile spermatozoa have a brief stay in the vagina before
      starting their ascent in the female reproductive tract. Vaginal spermatozoa have
      been targeted for contraception since ages. Spermicides and sperm immobilizers
      inactivate sperm immediately on deposition in the vagina, while they are placed
      in a rather 'ex-vivo' condition outside the body. Their need based usage, minimal
      systemic involvement; easy application, self-controlled reversibility and
      potential capability to obliterate sexually transmitted infections add
      significant value to contraception. We have reviewed here our recent endeavors in
      this important area of chemical contraception by using designed chemical
      synthesis approach to inhibit spermatozoa and infection. 

PMID- 25620227
TI  - Feasibility of male hormonal contraception: lessons from clinical trials and
      animal experiments.
AB  - The general interest in the availability of male contraceptives is on the
      increase across different cultures and ethnic backgrounds, due in part to the
      fact that men are now willing more than ever, to share the responsibility of
      family planning. Despite the expression of interest and tremendous advances in
      research however, a modern male hormonal contraceptive method has remained an
      elusive goal. Testosterone (T) alone, or in combination with a progestin
      currently provides the most promising lead to male hormonal contraception. The
      principle relies on enhanced negative feedback of exogenous T to suppress
      gonadotropins, thereby blocking the endocrine stimulus for the process of
      spermatogenesis. A serious drawback is the inconsistent suppression among men of
      different ethnic backgrounds. This has increased the quest for development to
      include other nonhormonal methods. In reality many obstacles still have to be
      overcome before an acceptable method is available. In this review, we highlight
      recent developments in male hormonal contraceptives methods. Based on our recent
      findings from animal experiment, we shed light on why the method is not achieving
      the intended results, and suggest possible ways forward. 

PMID- 25620228
TI  - Mechanisms of hormonal regulation of sertoli cell development and proliferation:
      a key process for spermatogenesis.
AB  - In adulthood, the main function of the testes is the production of male gametes.
      In this process, Sertoli cells are essential for sustained spermatogenesis,
      providing the developing germ cells with the physical and nutritional support
      required. The total number of Sertoli cells in adulthood determines the daily
      gamete production, since Sertoli cells can support only a limited number of
      developing germ cells. Considering that Sertoli cell proliferation only occurs
      during the immature period, proper development and proliferation of the Sertoli
      cells during the proliferative phase are crucial to male reproductive health in
      adulthood. The proliferation process of the Sertoli cells is finely regulated by
      an assortment of hormonal and paracrine/autocrine factors, which regulate the
      rate and extent of proliferation. In the present review, we discuss the most
      important hormonal and paracrine factors involved in the regulation of Sertoli
      cell proliferation, as well as the signaling mechanisms by which they exert their
      effects. 

PMID- 25620229
TI  - Effect of environmental contaminants on mammalian testis.
AB  - Exposure of humans and wildlife to pollutants released in the environment is a
      centre of attention nowadays. Many of these chemicals (generally referred to as
      environmental pollutants) have been shown to interfere with normal hormonal
      signalling and biological functions, leading to reproductive disorders or
      infertility, which has been a matter of concern within the recent decades. The
      present paper reviews adverse effects of these toxicants on mammalian testes,
      with emphasis on alteration of steroidogenesis, spermatogenesis, and
      histopathological effects. From the publications reviewed, it appears that
      environmental toxicants, especially heavy metals and organic chemicals of
      synthetic and microbiological origins, disrupt hormone production and action in
      the mammalian testes. Endocrine disruption leads to disorders of testicular
      function and thereby compromises the normal phenotypic development of male sexual
      characteristics, initiation and maintenance of spermatogenesis. The toxicants
      also induce impairment of testicular cells function, testicular histology, and
      sperm cells function directly. The release of the toxicants in the environment is
      still ongoing, despite alarming quantities that already exist in the atmosphere.
      If appropriate measures are not taken, their impact on the male reproductive
      function and especially on testicular function will be more serious. 

PMID- 25620230
TI  - Natural products as modulators of spermatogenesis: the search for a male
      contraceptive.
AB  - Population growth in the last century has raised important social and economic
      questions. Thus, current methods of fertility control have been under debate for
      a long period. Birth rates are essentially dependent on several environmental and
      social factors but women, who are great users of contraceptives, play a major
      role. Regulation of male fertility has been widely studied in recent years with
      the aim of developing a new male contraceptive for further inclusion of men's
      choice in family planning. Based on the ancient people techniques to control the
      birth rates, natural products appeared as a promising source for the development
      of a male contraceptive. Over the years, many plants and their main constituents
      have been studied in the search for their antifertility properties.
      Interestingly, some antispermatogenic effects have been reported. Herein, we will
      discuss the antispermatogenic properties of some natural products. We propose to
      discuss specific targets and sites of action of the selected natural products.
      Despite the advances in this field in the last years, the molecular mechanisms by
      which natural products can control fertility, need to be disclosed to develop an
      effective, reversible and safe male contraceptive and avoid undesired toxicity in
      other organs. To date, no natural-based male contraceptive is available in the
      commercial market, mostly due to the difficulty in reversing the effects of these
      products in male fertility. 

PMID- 25620231
TI  - Targeting mammalian spermatogenesis: a matter of support.

PMID- 25620232
TI  - EYA4 Acts as a New Tumor Suppressor Gene in Colorectal Cancer.
AB  - A previous genome-wide methylation array for colorectal cancer (CRC) identified
      aberrant promoter methylation of eyes absent 4 (EYA4). However, the correlations
      between EYA4 methylation and gene expression, the role played by EYA4 protein in
      colorectal carcinogenesis, and results of the gene-enrichment and functional
      annotation analysis have not yet been established. We analyzed the EYA4
      methylation status and found EYA4 promoter methylation in CRC cell lines (100%),
      CRC tissues (93.5%) and advanced adenoma tissues (50.7%), compared with normal
      mucosa (32.6%). There was a significant inverse correlation between EYA4
      methylation and expression. EYA4 transfection led to inhibition of cell
      proliferation in colony assays and xenograft studies. On performing the gene
      enrichment and functional annotation analysis, we observed that the
      differentially expressed genes have been associated with the Wnt and MAPK
      signaling pathways. Our results demonstrate that EYA4 is under epigenetic
      regulation in CRC. It is a candidate tumor suppressor gene that acts by inducing
      up-regulation of DKK1 and inhibiting the Wnt signaling pathway. In addition, EYA4
      methylation may be identified in stool samples and it serves as a potential stool
      biomarker for detection of advanced adenoma and CRC.

PMID- 25620233
TI  - Marine natural products.
AB  - This review covers the literature published in 2013 for marine natural products
      (MNPs), with 982 citations (644 for the period January to December 2013)
      referring to compounds isolated from marine microorganisms and phytoplankton,
      green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates,
      echinoderms, mangroves and other intertidal plants and microorganisms. The
      emphasis is on new compounds (1163 for 2013), together with the relevant
      biological activities, source organisms and country of origin. Reviews,
      biosynthetic studies, first syntheses, and syntheses that lead to the revision of
      structures or stereochemistries, have been included.

PMID- 25620234
TI  - Colorless chlorophyll catabolites in senescent florets of broccoli (Brassica
      oleracea var. italica).
AB  - Typical postharvest storage of broccoli (Brassica oleracea var. italica) causes
      degreening of this common vegetable with visible loss of chlorophyll (Chl). As
      shown here, colorless Chl-catabolites are generated. In fresh extracts of
      degreening florets of broccoli, three colorless tetrapyrrolic Chl-catabolites
      accumulated and were detected by high performance liquid chromatography (HPLC):
      two "nonfluorescent" Chl-catabolites (NCCs), provisionally named Bo-NCC-1 and Bo
      NCC-2, and a colorless 1,19-dioxobilin-type "nonfluorescent" Chl-catabolite
      (DNCC), named Bo-DNCC. Analysis by nuclear magnetic resonance spectroscopy and
      mass spectrometry of these three linear tetrapyrroles revealed their structures.
      In combination with a comparison of their HPL-chromatographic properties, this
      allowed their identification with three known catabolites from two other
      brassicacea, namely two NCCs from oil seed rape (Brassica napus) and a DNCC from
      degreened leaves of Arabidopsis thaliana.

PMID- 25620236
TI  - Highly regio- and diastereo-selective synthesis of novel tri- and tetra-cyclic
      perhydroquinoline architectures via an intramolecular [3 + 2] cycloaddition
      reaction.
AB  - A facile and efficient synthetic protocol was established for the construction of
      novel tri- and tetra-cyclic pyrrolo/pyrrolizinoquinoline architectures via the in
      situ formation of azomethine ylide followed by an intramolecular [3 + 2]
      cycloaddition reaction strategy. This protocol leads to the creation of two/three
      new rings and three/four contiguous stereocentres, in which one of them is a
      tetra-substituted carbon center, in a highly diastereoselective fashion with
      excellent yields. 

PMID- 25620235
TI  - ZnT2 is a critical mediator of lysosomal-mediated cell death during early mammary
      gland involution.
AB  - Mammary gland involution is the most dramatic example of physiological cell
      death. It occurs through an initial phase of lysosomal-mediated cell death (LCD)
      followed by mitochondrial-mediated apoptosis. Zinc (Zn) activates both LCD and
      apoptosis in vitro. The Zn transporter ZnT2 imports Zn into vesicles and
      mitochondria and ZnT2-overexpression activates cell death in mammary epithelial
      cells (MECs). We tested the hypothesis that ZnT2-mediated Zn transport is
      critical for mammary gland involution in mice. Following weaning, ZnT2 abundance
      increased in lysosomes and mitochondria, which paralleled Zn accumulation in each
      of these organelles. Adenoviral expression of ZnT2 in lactating mouse mammary
      glands in vivo increased Zn in lysosomes and mitochondria and activated LCD and
      apoptosis, promoting a profound reduction in MECs and alveoli. Injection of
      TNFalpha, a potent activator of early involution, into the mammary gland fat pads
      of lactating mice increased ZnT2 and Zn in lysosomes and activated premature
      involution. Exposure of cultured MECs to TNFalpha redistributed ZnT2 to lysosomes
      and increased lysosomal Zn, which activated lysosomal swelling, cathepsin B
      release, and LCD. Our data implicate ZnT2 as a critical mediator of cell death
      during involution and importantly, that as an initial involution signal, TNFalpha
      redistributes ZnT2 to lysosomes to activate LCD. 

PMID- 25620237
TI  - Applicant to Residency Program Translation Guide.

PMID- 25620239
TI  - Nanoparticle Carriers in Medicinal Chemistry and Pharmaceutical Sciences.

PMID- 25620238
TI  - Use of pressure in reversed-phase liquid chromatography to study protein
      conformational changes by differential deuterium exchange.
AB  - The market of protein therapeutics is exploding, and characterization methods for
      proteins are being further developed to understand and explore conformational
      structures with regards to function and activity. There are several spectroscopic
      techniques that allow for analyzing protein secondary structure in solution.
      However, a majority of these techniques need to use purified protein,
      concentrated enough in the solution to produce a relevant spectrum. In this
      study, we describe a novel approach which uses ultrahigh pressure liquid
      chromatography (UHPLC) coupled with mass-spectrometry (MS) to explore
      compressibility of the secondary structure of proteins under increasing pressure
      detected by hydrogen-deuterium exchange (HDX). Several model proteins were used
      for these studies. The studies were conducted with UHPLC in isocratic mode at
      constant flow rate and temperature. The pressure was modified by a backpressure
      regulator up to about 1200 bar. It was found that the increase of retention
      factors upon pressure increase, at constant flow rate and temperature, was based
      on reduction of the proteins' molecular molar volume. The change in the proteins'
      molecular molar volume was caused by changes in protein folding, as was revealed
      by differential deuterium exchange. The degree of protein folding under certain
      UHPLC conditions can be controlled by pressure, at constant temperature and flow
      rate. By modifying pressure during UHPLC separation, it was possible to achieve
      changes in protein folding, which were manifested as changes in the number of
      labile protons exchanged to deuterons, or vice versa. Moreover, it was
      demonstrated with bovine insulin that a small difference in the number of protons
      exchanged to deuterons (based on protein folding under pressure) could be
      observed between batches obtained from different sources. The use of HDX during
      UHPLC separation allowed one to examine protein folding by pressure at constant
      flow rate and temperature in a mixture of sample solution with minimal amounts of
      sample used for analysis. 

PMID- 25620240
TI  - Lipoic Acid: its antioxidant and anti-inflammatory role and clinical
      applications.
AB  - Lipoic acid (LA) is an antioxidant able to produce its effects in aqueous or
      lipophilic environments. Lipoate is the conjugate base of lipoic acid, and the
      most prevalent form of LA under physiological conditions. It presents a highly
      negative reduction potential, increases the expression of antioxidant enzymes and
      participates in the recycling of vitamins C and E. Due to these properties, LA is
      called the "universal antioxidant". LA is also involved with anti-inflammatory
      action, independently of its antioxidant activity. This review was carried out,
      aiming to identify, analyze, and rationalize the various clinical,
      physiopathological and/or physiological situations in which LA, through oral
      supplementation, was tested on human and animal (rats and mice) models. LA was
      mainly tested in cardiovascular diseases (CVD), obesity, pain, inflammatory
      diseases and aging. LA uses in CVD and obesity, in humans, are controversial. On
      the other hand, beneficial effects on inflammation and pain were observed. LA
      supplementation in animal models may prolong life, has neuroprotective effects
      and presents positive effects against cancer. Differences observed in human and
      animal models can be due, in part, to different treatments (LA combined with
      other antioxidants, different doses) and to the variety of biomarkers
      investigated in animal experiments. These results suggest the need for further
      clinical trials to guide health professionals regarding the safety of
      prescription of this supplement.

PMID- 25620241
TI  - Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer's
      disease: the NF-kappaB connection.
AB  - Oxidative stress and inflammatory response are important elements of Alzheimer's
      disease (AD) pathogenesis, but the role of redox signaling cascade and its cross
      talk with inflammatory mediators have not been elucidated in details in this
      disorder. The review summarizes the facts about redox-signaling cascade in the
      cells operating through an array of kinases, phosphatases and transcription
      factors and their downstream components. The biology of NF-kappaB and its
      activation by reactive oxygen species (ROS) and proinflammatory cytokines in the
      pathogenesis of AD have been specially highlighted citing evidence both from post
      mortem studies in AD brain and experimental research in animal or cell-based
      models of AD. The possibility of identifying new disease-modifying drugs for AD
      targeting NF-kappaBsignaling cascade has been discussed in the end. 

PMID- 25620242
TI  - Antibiotic prophylaxis in cesarean section and other surgical procedures: a
      Korean national assessment system.

PMID- 25620243
TI  - Electroanalysis of pM-levels of urokinase plasminogen activator in serum by
      phosphorothioated RNA aptamer.
AB  - Protein biomarkers of cancer allow a dramatic improvement in cancer diagnostics
      as compared to the traditional histological characterisation of tumours by
      enabling a non-invasive analysis of cancer development and treatment. Here, an
      electrochemical label-free assay for urokinase plasminogen activator (uPA), a
      universal biomarker of several cancers, has been developed based on the recently
      selected uPA-specific fluorinated RNA aptamer, tethered to a gold electrode via a
      phosphorothioated dA tag, and soluble redox indicators. The binding properties of
      the uPA-aptamer couple and interference from the non-specific adsorption of
      bovine serum albumin (BSA) were modulated by the electrode surface charge. A nM
      uPA electroanalysis at positively charged surfaces, complicated by the
      competitive adsorption of BSA, was tuned to the pM uPA analysis at negative
      surface charges of the electrode, being improved in the presence of negatively
      charged BSA. The aptamer affinity for uPA displayed via the binding/dissociation
      constant relationship correspondingly increased, ca. three orders of magnitude,
      from 0.441 to 367. Under optimal conditions, the aptasensor allowed 10(-12)-10(
      9) M uPA analysis, also in serum, being practically useful for clinical
      applications. The proposed strategy for optimization of the electrochemical
      protein sensing is of particular importance for the assessment and optimization
      of in vivo protein ligand binding by surface-tethered aptamers. 

PMID- 25620244
TI  - Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a
      pilot study in children with HIV-related brain disease and controls.
AB  - BACKGROUND: Corpus callosum thickness measurement on mid-sagittal MRI may be a
      surrogate marker of brain volume. This is important for evaluation of diseases
      causing brain volume gain or loss, such as HIV-related brain disease and HIV
      encephalopathy. OBJECTIVE: To determine if thickness of the corpus callosum on
      mid-sagittal MRI is a surrogate marker of brain volume in children with HIV
      related brain disease and in controls without HIV. MATERIALS AND METHODS: A
      retrospective MRI analysis in children (<5 years old) with HIV-related brain
      disease and controls used a custom-developed semi-automated tool, which divided
      the midline corpus callosum and measured its thickness in multiple locations.
      Brain volume was determined using volumetric analysis. Overall corpus callosum
      thickness and thickness of segments of the corpus callosum were correlated with
      overall and segmented (grey and white matter) brain volume. RESULTS: Forty-four
      children (33 HIV-infected patients and 11 controls) were included. Significant
      correlations included overall corpus callosum (mean) and total brain volume (P =
      0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02);
      premotor corpus callosum mean with total brain volume (P = 0.04) and white matter
      volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P =
      0.02) and sensory corpus callosum mean with total brain volume (P = 0.02).
      CONCLUSION: Corpus callosum thickness correlates with brain volume both in HIV
      infected patients and controls.

PMID- 25620245
TI  - Development and applications of universal H7 subtype-specific antibodies for the
      analysis of influenza H7N9 vaccines.
AB  - H7N9 is a newly emerged avian influenza virus with a relatively high mortality
      rate in humans. At this time, there is no licensed vaccine for human protection.
      Development of analytical tools for H7N9 vaccine could facilitate vaccine
      development. Here, a universally conserved epitope in all H7 hemagglutinin (HA)
      sequences was identified through comprehensive bioinformatics analyses. The
      peptide epitope, RSGSSFYAEMK, (aa positions 149 to 159), is located on the head
      of the HA molecule. Antibodies generated against this universal H7 epitope were
      remarkably specific against H7 viral sequence with no detectable cross-reactivity
      to other HA subtypes. A new immunoblotting assay based on the universal H7
      antibody was developed and compared with the traditional single radial
      immunodiffusion assay (SRID) for potency analyses of candidate H7N9 vaccines.
      This new assay was more sensitive and rapid compared to SRID. In addition to
      statistically acceptable precision and reproducibility, the new assay differs
      from many other alternative potency assays for influenza vaccine in that it is
      potentially stability-indicating, which is an important requirement for industry
      vaccine stability studies analyses. Furthermore, the robustness of this new assay
      was demonstrated by the quantitative determination of HA content in four H7N9
      vaccines (split or inactivated) from different manufacturers. 

PMID- 25620246
TI  - Reply to letter to the editor.

PMID- 25620247
TI  - Predicting localised measles outbreak potential in Australia.
AB  - INTRODUCTION: Australia has achieved measles elimination as announced in March
      2014 by the WHO Western Pacific Regional Committee, based on several lines of
      evidence. However, despite strong national evidence for elimination, there
      remains substantial regional variation in vaccine coverage, has resulted in
      recent outbreaks and potential for increased frequency in the future. METHODS: In
      this study, we apply a multiple cohort model of measles immunity, stratified by
      age and local geographic area to predict trends in the measles reproduction
      number R. In addition, we use branching process models of outbreak risks to
      predict state-level probabilities of the occurrence of measles outbreaks over the
      next 20 years. RESULTS: Our results suggest increasing risks of large measles
      outbreaks over this period, in particular in the states of Queensland and New
      South Wales. In addition, there is wide variation in predicted R values by
      smaller geographic areas, although uncertainty in age-specific immunity limits
      the precision of our results. DISCUSSION: Our predictions align with observed
      outbreaks in Australian states and suggest our approach to determining future
      outbreak risks could be applied more widely in elimination or near-elimination
      settings.

PMID- 25620248
TI  - Safe administration of a gelatin-containing vaccine in an adult with galactose
      alpha-1,3-galactose allergy.
AB  - Immunoglobulin (Ig) E antibodies to galactose-alpha-1,3-galactose (alpha-Gal) are
      associated with delayed anaphylaxis to mammalian food products and gelatin-based
      foods (Commins et al., J Allergy Clin Immunol 2009;123:426; Caponetto et al., J
      Allergy Clin Immunol Pract 2013;1:302). We describe a patient with alpha-Gal
      allergy who successfully tolerated the live zoster vaccine and we review
      anaphylactic reactions reported to this vaccine. Our patient, who tolerated a
      vaccine containing the highest gelatin content, is reassuring but continued
      safety assessment of gelatin-containing vaccines for this patient cohort is
      recommended as there are multiple factors for this patient cohort that influence
      the reaction risk. 

PMID- 25620249
TI  - [Experts consensus of the evaluation on the statin drugs safty].

PMID- 25620250
TI  - [Chinese expert recommendations for perioperative beta-blocker therapy in
      patients undergoing noncardiac surgery].

PMID- 25620251
TI  - [Clinical analysis of 160 cases of statin-induced myopathy].
AB  - OBJECTIVE: To analyze the clinical features of statin-induced myopathy. METHOD:
      The statin-induced myopathy case reported as adverse drug reaction (ADR) to the
      Beijing Center for ADR Monitoring during January 2007 to December 2012 was
      summarized, patients were divided to myopathy group and rhabdomyolysis group,
      according to the absence or presence of rhabdomylysis. The clinical
      characteristics, medication history and outcome were compared between the two
      groups. RESULTS: A total of 160 statin-induced myopathy cases (54 in
      rhabdomyolysis group (33.8%) and 106 cases in myopathy group (66.3%)) were
      collected from the database (mean age: (64.22 +/- 13.55) years old, 51.2% male, n
      = 82). The ADR occurred immediately after the first medication and up to 4 years
      after medication. Observed clinical features were myalgia, myositis,
      asymptommatic creatine kinase (CK) elevation or rhabdomyolysis. The average age
      were (68.54 +/- 15.41) years old in rhabdomylysis group and (62.02 +/- 12.41)
      years old in myopathy group (P = 0.004). There was no gender difference between
      the rhabdomylysis group and myopathy group (P = 0.406) . Twenty-four cases
      (44.4%) in rhabdomyolysis group and 26 cases (16.5%) in myopathy group were
      treated with high dose statin (P < 0.001). Percent of simvastatin treatment was
      significantly higher in rhabdomyolysis group (70.4% (38/54) ) than in myopathy
      group (32.1% (34/106), P < 0.001). Spearman correlation analysis showed that age,
      high-dose statin treatment and simvastatin use were all positively correlated
      with rhabdomylysis (P < 0.001), and the correlation coefficients (r value) were
      0.305, 0.290 and 0.364, respectively. Four patients (aged from 71 to 85 years)
      died because of ADR and all 4 cases received high-dose statin treatment, 3 of
      them suffered from complex combined diseases, acute disease progression and
      complex multiple drug use history. CONCLUSIONS: Severe statin-induced myopathy,
      like rhabdomyolysis, is more likely to occur in old patients, in patients taking
      high-dose statin, especially simvastatin.

PMID- 25620252
TI  - [Efficacy and safety comparison of different statins in elderly patients].
AB  - OBJECTIVE: To compare the efficacy and safety of atorvastatin, rosuvastatin and
      xuezhikang capsule in elderly. METHODS: A total of 314 60-to-94-year-old (average
      (73.6 +/- 7.9) years old) patients who were given different doses and types of
      statins were divided into three groups: the atorvastatin group (108 patients),
      the rosuvastatin group (104 patients) and the xuezhikang capsule group (102
      patients). The serum TG, TC, LDL-C, HDL-C,ALT and CK were examined before and
      after the treatment which lasted for at least 4 weeks. All patients were divided
      into moderate risk group (13, 12 and 21 patients respectively in 3 groups); high
      risk group (40, 44 and 48 patients respectively in 3 groups) and very high risk
      group (55, 48 and 33 patients respectively in 3 groups ) according to guidelines
      on prevention and treatment of dyslipidemia in chinese adults (2007 version). The
      rate of reaching target goal and the dose when reaching target levels in
      different risk stratification groups were calculated and compared. RESULTS: Serum
      TC, LDL-C and non-HDL-C were significantly reduced after the 4-week-treatment in
      all the three groups (P < 0.01). Serum LDL-C level before and after treatment
      were (3.14 +/- 0.78)mmol/L vs. (2.14 +/- 0.65)mmol/L in atorvastatin group (the
      arevage dose was (16.4 +/- 4.8)mg/d), (2.92 +/- 0.77)mmol/L vs. (1.96 +/-
      0.55)mmol/L in rosuvastatin group (the arevage dose was (8.7 +/- 3.0) mg/d), and
      (2.70 +/- 0.62)mmol/L vs. (2.16 +/- 0.61) mmol/L in xuezhikang capsule group (the
      arevage dose was (0.9 +/- 0.3) g/d ). Among all the three groups of patients, the
      cases of reaching target levels of LDL-C were 13, 11 and 20 in patients at
      moderate risk, were 38(95.0%), 38(86.4%) and 40 (83.3%) in patients at high risk,
      and were 22(40.0%), 30(62.5%) and 17(51.5%) in patients at very high risk. There
      were no statistical differences in the rate of reaching target levels of LDL-C,
      non-HDL-C and TC in the three groups and at different risks (P > 0.05). One
      patient in the atorvastatin group showed ALT level elevation >3 times of the
      upper limit of normal value, there was no patient with CK level elevation >5
      times of the upper limit of normal value. CONCLUSION: Atorvastatin, rosuvastatin
      and xuezhikang capsule at low dose and/or standard dose are effective and safety
      in elderly patients.

PMID- 25620253
TI  - [Association between apolipoprotein A1-75 bp gene polymorphisms and risk for
      dyslipidemia and coronary artery disease].
AB  - OBJECTIVE: To explore the relationship between the apolipoprotein ApoA1-75 bp
      polymorphism and risk for dyslipidemia and coronary artery disease (CAD).
      METHODS: A total of 723 patients (mean age (62.4 +/- 10.2) years old) admitted to
      Guangdong General Hospital from 2011 to 2013 were enrolled. They were subdivided
      into CAD group (n = 444) and non-CAD (n = 279) group according to the result of
      coronary angiography (CAG). Clinical data including the profiles of lipids, -75
      bp gene polymorphisms and Gensini scores were analyzed to determine the
      correlation between -75 bp gene polymorphisms, lipid profile and CAD. RESULT:
      Frequency of male gender, history of diabetes and smoking, TC, TG, LDL-C and ApoB
      level were significantly higher and HDL-C level was significantly lower in CAD
      group than in non-CAD group (all P < 0.05). Frequency of A allele was
      significantly lower in CAD group than in non-CAD group (43.7% (194/444) vs. 56.6%
      (158/279) , P = 0.003). The ApoA1-75 bp gene polymorphism was significantly
      correlated with CAD (P < 0.005). Multivariate logistic regression analysis showed
      that -75 bp gene polymorphism mutation (OR = 0.649, P = 0.021) is an independent
      protective factor for coronary heart disease. CONCLUSION: ApoA1-75 bp gene
      polymorphism is linked with risk of dyslipidemia and CAD.

PMID- 25620254
TI  - [Impact of pre-operative uric acid on acute kidney injury after cardiac surgery
      in elderly patients].
AB  - OBJECTIVE: To investigate the impact of pre-operative uric acid on acute kidney
      injury (AKI) after cardiac surgery in elderly patients. METHODS: Clinical data
      were collected from 936 elderly patients (age >= 60 years) undergoing cardiac
      surgery with cardiopulmonary bypass in Guangdong General Hospital between January
      2005 and May 2011. The baseline serum creatinine was defined as the latest serum
      creatinine before surgery, and AKI was diagnosed according to RIFLE criteria.
      Patients were divided into three groups according to the sex-specific cutoff
      values of serum uric acid tertiles (group A: <= 384.65 umol/L in men, and <=
      354.00 umol/L in women; group B:384.66-476.99 umol/L in men and 354.01-437.96
      umol/L in women; group C: >= 477.00 umol/L in men and >= 437.97 umol/L in women).
      Multivariate logistic regression analysis was used to analyze the independent
      risk factors for AKI. RESULTS: Among 936 elderly patients, 576 cases (61.5%)
      developed AKI. Mean uric acid concentration was higher in AKI patients than in
      Non-AKI patients ( (436.6 +/- 119.1) umol/L vs. (398.0 +/- 107.2) umol/L, P <
      0.001). The incidence of AKI was 56.1% (175/312) in group A, 56.3% (175/311) in
      group B, 72.2% (226/313) in group C (P < 0.001). Multiple logistic regression
      analysis showed that, after adjusted for age, gender, co
      morbidities(hypertension, diabetes mellitus, cerebrovascular disease, chronic
      obstructive pulmonary disease), previous cardiac surgery, eGFR<60 ml*min(-1)
      *1.73 m(-2), heart function >= 3 (NYHA), positive urine protein, combination of
      coronary artery bypass grafting and valvular surgery, cardiopulmonary bypass
      operation time, aortic cross-clamping time, pre-operative angiotensin converting
      enzyme inhibitor or angiotensin II receptor blockers and lipid-lowering drugs
      use, early postoperative angiotensin converting enzyme inhibitor or angiotensin
      II receptor blockers, diuretics and digoxin use, post-operation central venous
      pressure, risk of post operative AKI was significantly higher in group C than in
      group A (OR:1.897, 95%CI: 1.270-2.833, P = 0.002). CONCLUSION: Pre-operative
      elevated uric acid is an independent risk factor of AKI after cardiac surgery in
      elderly patients.

PMID- 25620255
TI  - [Diagnostic value of cardiac magnetic resonance in patients with acute viral
      myocarditis].
AB  - OBJECTIVE: To assess the diagnostic value of cardiac magnetic resonance (CMR) in
      patients with acute viral myocarditis. METHODS: Thirty patients with suspected
      acute viral myocarditis admitted in first people's hospital of Shunde from June
      2011 to June 2013 were included in this prospective study. The diagnostic
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and accuracy of acute viral myocarditis were evaluated by clinical
      diagnosis. Diagnostic value among different scan methods and Lake Louise criteria
      were compared. RESULTS: Acute viral myocarditis was diagnosed in 63.33% (19/30)
      patients.Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy
      within the overall cohort were 57.89%, 72.73%, 78.57%, 50.00%, 63.33%,
      respectively by edema imaging (ER).Values for sensitivity, specificity, PPV, NPV,
      and diagnostic accuracy within the overall cohort were 78.95%, 63.64%, 78.95%,
      63.64%, 73.33%, respectively using global relative enhancement (gRE).Values for
      sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall
      cohort were 78.95%, 54.55%, 75.00%, 60.00%, 70.00%, respectively using late
      gadolinium enhancement (LGE) criteria.Values for sensitivity, specificity, PPV,
      NPV, and diagnostic accuracy within the overall cohort were 84.21%, 81.82%,
      88.89%, 75.00%, 83.33% using Lake Louise criteria. The sensitivity, specificity,
      PPV, NPV, and diagnostic accuracy using Lake Louise criteria were significantly
      higher than using ER, gRE, LGE alone(all P < 0.05).Specificity was higher using
      ER than using gRE and LGE (both P < 0.05). The sensitivity, NPV, and diagnostic
      accuracy were significantly higher using gRE than using ER (all P < 0.05) and was
      similar as using LGE (all P > 0.05). CONCLUSION: Cardiac magnetic resonance is an
      excellent imaging modality for the diagnosis of acute viral myocarditis.

PMID- 25620256
TI  - [MicroRNA-210 mediates the protective effect of rosuvastatin on human mesenchymal
      stem cells apoptosis induced by tumor necrosis factor-alpha].
AB  - OBJECTIVE: To explore the effect and mechanism of rosuvastatin on tumor necrosis
      factor-alpha induced human mesenchymal stem cells (MSCs) apoptosis. METHOD: Human
      MSCs were treated as follows: (1) culture medium; (2) TNF-alpha (20 ug/ml) for 6
      h; (3) rosuvastatin (20 umol/L) for 24 h; (4) rosuvastatin (20 umol/L) for 24 h
      followed by TNF-alpha (20 ug/ml) for 6 h; (5) TNF-alpha+rosuvastatin+50 nmol/L
      antago-miRNA; (6) TNF-alpha+rosuvastatin+100 nmol/L antago-miRNA. Cell survival
      and apoptosis were determined by MTT, TUNEL and caspase-3 activity assay. The
      changes of miRNA-210 in each group were detected with quantitative PCR. RESULT:
      TNF-alpha significantly induced human MSCs apoptosis in a concentration-dependent
      manner, and pretreatment with rosuvastatin significantly reduced MSCs apoptosis
      (caspase-3 assay: TNF-alpha+Statin group vs. TNF-alpha group: (1.63 +/- 0.25) vs.
      (2.05 +/- 0.36), P < 0.05). Meanwhile, TNF-alpha progressively reduced the
      expression of miRNA-210 in human MSCs in a dose-dependent manner, while the miRNA
      210 expression was significantly upregulated in TNF-alpha+Statin group (P <
      0.05). The protective effect of rosuvastatin on TNF-alpha induced MSCs apoptosis
      was largely abolished by co-treatment with 100 nmol/L antago-miRNA (TUNEL:TNF
      alpha + Statin + antago-miR group vs. TNF-alpha + Statin group: (42.58 +/- 6.71)
      % vs. (16.87 +/- 9.27) %, P < 0.05). CONCLUSION: Pretreatment with rosuvastatin
      can significantly improve the viability of human MSCs after TNF-alpha injury, the
      protective mechanism of rosuvastatin is partly mediated through miRNA-210 up
      regulation.

PMID- 25620257
TI  - [Kindlin-2 regulates migration and adhesion of vascular smooth muscle cells via
      beta1-integrin].
AB  - OBJECTIVE: To explore the effects of Kindlin-2 RNA interference on vascular
      smooth muscle cells (VSMCs) migration, adhesion and beta1-integrin as well as the
      relationship between Kindlin-2 and beta1-integrin. METHODS: Primary VSMCs were
      cultured, infected with Kindlin-2 siRNA lentiviral vectors.VSMCs were divided
      into three groups:the blank control group, the negative control group and the
      Kindlin-2 siRNA group. The ability of VSMCs migration was measured by Transwell
      experiment and wound healing assay. The ability of VSMCs adhesion to extracelluar
      matrix was determined by cell-extracelluar matrix adhesion assay. The Kindlin-2
      and beta1-integrin mRNA and protein expression levels were detected by real-time
      quantitative PCR and Western blot. Total beta1-integrin and active beta1-integrin
      expression on the surface of VSMCs was evaluated by flow cytometry. RESULTS: The
      efficiency of Kindlin-2 siRNA lentivirus infected VSMCs was more than 90%. The
      number of VSMCs migration in the Kindlin-2 siRNA group was significantly lower
      than that of the blank control group and the negative group (all P < 0.05).
      Moreover, the distance of VSMCs migration was shorter than that of the blank
      control group and the negative group (all P < 0.05). The number of VSMCs adhesion
      to collagen I was less than that of the blank control group and the negative
      group (all P < 0.05). A(590 nm) of the Kindlin-2 siRNA group was also lower than
      that of the blank control group and the negative group (all P < 0.05). Compared
      with the blank control group, the expression level of Kindlin-2 mRNA in the
      Kindlin-2 siRNA group decreased 47% (P < 0.05), but the expression level of beta1
      integrin mRNA remained unchanged. The Kindlin-2 protein level in the Kindlin-2
      siRNA group was lower than that of the blank control group and the negative group
      (all P < 0.05). beta1-integrin protein level was similar among the three groups.
      Activated beta1-integrin on the surface of VSMCs in the Kindlin-2 siRNA group was
      lower than that of the blank control group and the negative group (all P <
      0.05).However, the expression level of total beta1-integrin on the VSMCs surface
      was similar among the three groups. CONCLUSION: Kindin-2 can regulate VSMCs
      migration and adhesion and activate beta1-integrin on the surface of VSMCs.

PMID- 25620258
TI  - [Protective effects of antioxidants on chronic intermittent hypoxia-induced
      cardiac remodeling in mice].
AB  - OBJECTIVE: Chronic intermittent hypoxia (CIH) animal model was used to mimic the
      status of obstructive sleep apnea (OSA) in order to investigate the pathological
      mechanism of CIH-induced cardiac remodeling and observe the protective effect of
      antioxidants. METHODS: FVB mice (8-10 weeks-old) were randomly divided into
      control (saline, i.p.) group and CIH group, reduced form of nicotinamide adenine
      dinucleotide phosphate oxidase inhibitor, apocynin (APO, 3 mg*kg(-1)*d(-1), i.p.)
      alone or CIH+APO, SOD mimic MnTMPyP (SODM, 5 mg*kg(-1)*d(-1), i.p.) alone or
      CIH+SODM (n = 5 each). After 4 weeks, cardiac function and structure were
      determined by echocardiography, cardiac inflammation, apoptosis, cardiac fibrosis
      and cardiac MDA contents were examined by Western blot and chemical-biological
      methods, respectively. RESULTS: (1) Heart weight, LVIDd and LVIDs were increased
      while LVEF and FS were reduced in CIH group compared to control group (all P <
      0.05). (2) Myocardial protein expression of ANP and VCAM-1 was significantly
      upregulated, myocardial MDA content and apoptosis as well as myocardial fibrosis
      marker CTGF and PAI-1 were increased in CIH group compared to control group (all
      P < 0.05). (3) Above parameters were similar between APO and CIH+APO as well as
      SODM and CIH+SODM (all P > 0.05). CONCLUSION: CIH could induce cardiac remodeling
      and CIH-induced cardiac inflammation, cardiac oxidative injury, cardiac apoptosis
      and cardiac fibrosis serve as the pathological mechanisms of CIH-induced cardiac
      remodeling. The protective effects of the two antioxidants suggest that the main
      mechanism of CIH-induced cardiac injury is oxidative stress.

PMID- 25620259
TI  - [Slfn1 inhibited the migration of endothelial progenitor cells in vitro].
AB  - OBJECTIVE: To explore the effect of Schlafen 1 (Slfn1) on the migration of
      endothelial progenitor cells (EPCs). METHODS: Rat bone marrow derived EPCs were
      isolated and cultured. Ad-Slfn1, ShRNA-Slfn1, ShRNA-control and Ad-control were
      transfected into EPCs respectively. The mRNA expression of Slfn1 and Cyclin D1
      was examined by reverse transcriptase-PCR, and their protein expression was
      detected by Western blot. The migration of EPCs was examined by a modified Boyden
      chamber assay.EPCs cell cycle was determined using flow cytometry analysis.
      RESULTS: Forty-eight hours after ShRNA-Slfn1 transfection, the mRNA and protein
      expression of Slfn1 in EPCs was significantly down-regulated compared to ShRNA
      control EPCs (P < 0.05). Transfection of Ad-Slfn1 reversed these
      changes.Overexpression of Slfn1 reduced the migration capacity of EPCs while the
      silencing of Slfn1 by shRNA-Slfn1 increased the migration capacity of EPCs.In
      addition, cell cycle was arrested at G1 phase in Slfn1 overexpression group while
      transfection of shRNA-Slfn1 reversed these responses.Interestingly, the mRNA and
      protein expression of Cyclin D1 was significantly up-regulated after shRNA-Slfn1
      transfection compared to ShRNA-control group (all P < 0.05), but overexpression
      of Slfn1 reversed these results, suggesting Cyclin D1 was involved in regulating
      EPCs cell cycle via Slfn1 signaling. CONCLUSIONS: Slfn1 could reduce the
      migration capacity of EPCs via Cyclin D1 pathway.

PMID- 25620260
TI  - [Changes in the diagnosis and treatment of hospitalized patients with acute
      coronary syndrome from 2006 to 2012 in China].
AB  - OBJECTIVE: To observe the changes in the diagnosis and treatment of hospitalized
      patients with acute coronary syndrome (ACS) from 2006 to 2012 in China. METHODS:
      Hospitalized patients with ACS in 2006 from 65 hospitals distributed in 31
      provinces, autonomous regions, and municipalities (data derived from the BRIG
      project phase I study, n = 3 323) and hospitalized in 2012 from 34 hospitals
      distributed in 21 provinces, autonomous regions, and municipalities (data derived
      from the BRIG project phase III study, n = 3 391) were included. Patients with
      susceptible ACS, patients admitted to hospital due to trauma, or patients
      participated in any drug clinical trials were excluded. Only patients with
      complete data were analyzed. Data between 3 124 ACS patients from BRIG project-I
      and 3 124 ACS patients from BRIG project-III were compared. RESULTS: (1) The ACS
      patients hospitalized in 2012 were younger than those hospitalized in 2006 ((61.9
      +/- 11.2) years vs. (64.7 +/- 11.5) years, P < 0.01), and the percentage of
      patients <= 60 years was higher in patients hospitalized in 2012 ((42.5% (1 327/3
      124)) compared with those hospitalized in 2006 (32.1% (1 004/3 124), P <
      0.05).(2) The percentages of ACS patients complicated with hypertension ((61.2%
      (1 853/3 124) vs. 53.0% (1 655/3 124)), diabetes (24.3% (760/3 124) vs. 16.4%
      (513/3 124)), and hypercholesterolemia (20.3% (633/3 124) vs. 6.3% (197/3 124))
      were consistently higher in ACS patients hospitalized in 2012 than in
      hospitalized ACS patients in 2006 (all P < 0.01).(3) The rate of coronary
      angiogram examination increased from 28.6% (894/3 124) in 2006 to 68.6% (2 144/3
      124) in 2012 (P < 0.01) . Moreover, the rate of intervention treatment was
      increased from 24.6% (770/3 124) in 2006 to 51.0% (1 594/3 124) in 2012 (P <
      0.01). (4) The administration rate of aspirin (95.2% (2 975/3 124) vs. 91.7% (2
      864/3 124) ), clopidogrel (85.6% (2 673/3 124) vs. 42.2% (1 318/3 124) ), and
      statins (90.0% (2 812/3 124) vs. 69.8% (2 180/3 124) ) was significantly higher
      in 2012 than in 2006 (all P < 0.01). CONCLUSION: Compared with 2006, there is a
      trend of younger onset age for ACS and higher proportions of complicated
      cardiovascular diseases, as well as improved diagnosis and treatment strategies
      for Chinese ACS patients in 2012.

PMID- 25620261
TI  - [Management of pulmonary arterial hypertension associated with congenital heart
      disease with specific pulmonary arterial hypertension vasoactive drugs combined
      with transcatheter closure strategy:a case report].

PMID- 25620262
TI  - [Giant cavernous hemangioma in the pericardial cavity: a case report].

PMID- 25620263
TI  - [Restoring sinus rhythm from delayed third degree atrioventricular block after
      ventricular septal defect interventional therapy: a case report].

PMID- 25620264
TI  - [Intravascular ultrasound-guided percutaneous coronary intervention for chronic
      total occlusion of left anterior descending artery:a case report].

PMID- 25620265
TI  - [Risk factors prevalence for coronary heart disease in human immunodeficiency
      virus infected individuals].

PMID- 25620266
TI  - [p66Shc and cardiovascular diseases].

PMID- 25620267
TI  - [Role of cardiac magnetic resonance in the diagnosis and treatment of ventricular
      arrhythmia].

PMID- 25620268
TI  - Anthroposophic lifestyle and salivary cortisol are associated with a lower risk
      of sensitization during childhood.
AB  - BACKGROUND: Infants from anthroposophic families have low cortisol levels and low
      risk of IgE-sensitization during first 2 years of life. Our aim was to study the
      impact of an anthroposophic lifestyle and cortisol levels at 6 months on allergy
      sensitization up to age 5 years. METHODS: A total of 507 families participated
      from maternal healthcare centers. Parental lifestyle was categorized as
      anthroposophic, partly anthroposophic, or non-anthroposophic. Blood samples for
      analyzes of sensitization were obtained from parents at inclusion and from
      children at 6, 12, 24, and 60 months. Salivary samples were collected at home at
      6 months. RESULTS: Sensitization increased from 2.9% to 26.0% in the
      anthroposophic group, from 8.4% to 26.8% in the partly anthroposophic group, and
      from 19.1% to 44.1% in the non-anthroposophic group. Children from anthroposophic
      families had lower cortisol levels in the morning, afternoon, and evening. The
      odds ratio (OR) for anthroposophic lifestyle was always <1 and lowest at 12
      months (OR, 0.10; 95% CI, 0.03-0.36). Adjusting for cortisol levels at 6 months
      increased these ORs at 12 and 24 months. At the same ages, ORs for sensitization
      were elevated also for cortisol levels at 6 months. Analyzes in children not
      sensitized at 6 months confirmed the cortisol-related risk of sensitization.
      CONCLUSIONS: Children from families with an anthroposophic lifestyle have lower
      risk than comparisons of developing sensitization up to 5 years. This risk is
      partially explained by low cortisol levels during infancy. High cortisol levels
      at 6 months predict sensitization up to 24 months.

PMID- 25620269
TI  - Clinical outcomes following neoadjuvant cisplatin-based chemotherapy for bladder
      cancer in elderly compared with younger patients.
AB  - Bladder cancer is a disease of the elderly. Older patients might potentially be
      undertreated due to assumptions about benefit versus risk. Our objective was to
      determine outcomes in older patients receiving neoadjuvant chemotherapy for
      muscle-invasive bladder cancer (MIBC). We hypothesised that appropriately
      selected elderly patients (>=70 years) with MIBC could have similar clinical
      outcomes, and be safely treated, with standard neoadjuvant chemotherapy prior to
      definitive cystectomy or radiotherapy. We utilised a single institution case
      series analysis of patients with T2-4a N0 M0 transitional cell carcinoma of the
      bladder treated with cisplatin-based neoadjuvant chemotherapy between 2005 and
      2011. Eighty-three patients were eligible. Median age was 68 (range 48-80), 33
      patients (40%) were >=70 years. Overall survival at 3 years was 65.8% (>=70) and
      63.2% (<70) (P = 0.653), relapse-free survival at 3 years was 61.6% and 54.8%
      respectively (P = 0.471). The rates going forward to definitive local therapy
      (87.9% >= 70 and 84.0% < 70) and the pathological complete response rate (31.3%
      >= 70 and 40% < 70) were similar. Disease relapse rate was also similar (63.6% >=
      70 vs. 60% < 70, P = 0.906). Elderly patients with good functional status and
      limited comorbidities diagnosed with MIBC receiving standard neoadjuvant
      chemotherapy followed by cystectomy or radiotherapy can have similar clinical
      outcomes as their younger counterparts. Prospective studies evaluating the
      optimum curative management in this elderly population are warranted. 

PMID- 25620270
TI  - On the challenge of exploring the evolutionary trajectory from phosphotriesterase
      to arylesterase using computer simulations.
AB  - The ability to design effective enzymes presents a fundamental challenge in
      biotechnology and also in biochemistry. Unfortunately, most of the progress on
      this field has been accomplished by bringing the reactants to a reasonable
      orientation relative to each other, rather than by rational optimization of the
      polar preorganization of the environment, which is the most important catalytic
      factor. True computer based enzyme design would require the ability to evaluate
      the catalytic power of designed active sites. This work considers the evolution
      from a phosphotriesterase (with the paraoxon substrate) to arylesterase (with the
      2-naphthylhexanoate (2NH) substrate) catalysis. Both the original and the evolved
      enzymes involve two zinc ions and their ligands, making it hard to obtain a
      reliable quantum mechanical description and then to obtain an effective free
      energy sampling. Furthermore, the options for the reaction path are quite
      complicated. To progress in this direction we started with DFT calculations of
      the energetics of different mechanistic options of cluster models and then used
      the results to calibrate empirical valence bond (EVB) models and to generate
      properly sampled free energy surfaces for different mechanisms in the enzyme.
      Interestingly, it is found that the catalytic effect depends on the Zn-Zn
      distance making the mechanistic analysis somewhat complicated. Comparing the
      activation barriers of paraoxon and the 2NH ester at the beginning and end of the
      evolutionary path reproduced the observed evolutionary trend. However, although
      our findings provide an advance in exploring the nature of promiscuous enzymes,
      they also indicate that modeling the reaction mechanism in the case of enzymes
      with a binuclear zinc center is far from trivial and presents a challenge for
      computer-aided enzyme design. 

PMID- 25620272
TI  - Potentiated processing of negative feedback in depression is attenuated by
      anhedonia.
AB  - BACKGROUND: Although cognitive theories of depression have postulated enhanced
      processing of negatively valenced information, previous EEG studies have shown
      both increased and reduced sensitivity for negative performance feedback in MDD.
      To reconcile these paradoxical findings, it has been speculated that sensitivity
      for negative feedback is potentiated in moderate MDD, but reduced in highly
      anhedonic subjects. The goal of this study was to test this hypothesis by
      analyzing the feedback-related negativity (FRN), frontomedial theta power (FMT),
      and source-localized anterior midcingulate cortex (aMCC) activity after negative
      feedback. METHODS: Fourteen unmedicated participants with Major Depressive
      Disorder (MDD) and 15 control participants performed a reinforcement learning
      task while 128-channel Electroencephalogram (EEG) was recorded. FRN, FMT, and
      LORETA source-localized aMCC activity after negative and positive feedback were
      compared between groups. RESULTS: The MDD group showed higher FRN amplitudes and
      aMCC activation to negative feedback than controls. Moreover, aMCC activation to
      negative feedback was inversely related to self-reported anhedonia. In contrast,
      self-reported anxiety correlated with feedback-evoked frontomedial theta (FMT)
      within the depression group. CONCLUSIONS: The present findings suggest that,
      among depressed and anxious individuals, enhanced processing of negative feedback
      occurs relatively early in the information processing stream. These results
      extend prior work and indicate that although moderate depression is associated
      with elevated sensitivity for negative feedback, high levels of anhedonia may
      attenuate this effect.

PMID- 25620273
TI  - Active eosinophilic esophagitis is characterized by epithelial barrier defects
      and eosinophil extracellular trap formation.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing
      to an eosinophil-predominant inflammation. Activated eosinophils generate
      eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of
      an impaired barrier function in EoE that might allow pathogens to invade the
      esophagus. This study aimed to investigate the presence and distribution of EETs
      in esophageal tissues from EoE patients and their association with possible
      epithelial barrier defects. METHODS: Anonymized tissue samples from 18 patients
      with active EoE were analyzed. The presence of DNA nets associated with
      eosinophil granule proteins forming EETs and the expression of filaggrin, the
      protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI),
      antimicrobial peptides, and cytokines were evaluated by confocal microscopy
      following immune fluorescence staining techniques. RESULTS: Eosinophil
      extracellular trap formation occurred frequently and was detected in all EoE
      samples correlating with the numbers of infiltrating eosinophils. While the
      expression of both filaggrin and LEKTI was reduced, epithelial antimicrobial
      peptides (human beta-defensin-2, human beta-defensin-3, cathelicidin LL-37,
      psoriasin) and cytokines (TSLP, IL-25, IL-32, IL-33) were elevated in EoE as
      compared to normal esophageal tissues. There was a significant correlation
      between EET formation and TSLP expression (P = 0.02) as well as psoriasin
      expression (P = 0.016). On the other hand, a significant negative correlation was
      found between EET formation and LEKTI expression (P = 0.016). CONCLUSION: Active
      EoE exhibits the presence of EETs. Indications of epithelial barrier defects in
      association with epithelial cytokines are also present which may have contributed
      to the activation of eosinophils. The formation of EETs could serve as a firewall
      against the invasion of pathogens.

PMID- 25620271
TI  - Sphingolipids and mitochondrial apoptosis.
AB  - The sphingolipid family of lipids modulate several cellular processes, including
      proliferation, cell cycle regulation, inflammatory signaling pathways, and cell
      death. Several members of the sphingolipid pathway have opposing functions and
      thus imbalances in sphingolipid metabolism result in deregulated cellular
      processes, which cause or contribute to diseases and disorders in humans. A key
      cellular process regulated by sphingolipids is apoptosis, or programmed cell
      death. Sphingolipids play an important role in both extrinsic and intrinsic
      apoptotic pathways depending on the stimuli, cell type and cellular response to
      the stress. During mitochondrial-mediated apoptosis, multiple pathways converge
      on mitochondria and induce mitochondrial outer membrane permeabilization (MOMP).
      MOMP results in the release of intermembrane space proteins such as cytochrome c
      and Apaf1 into the cytosol where they activate the caspases and DNases that
      execute cell death. The precise molecular components of the pore(s) responsible
      for MOMP are unknown, but sphingolipids are thought to play a role. Here, we
      review evidence for a role of sphingolipids in the induction of mitochondrial
      mediated apoptosis with a focus on potential underlying molecular mechanisms by
      which altered sphingolipid metabolism indirectly or directly induce MOMP. Data
      available on these mechanisms is reviewed, and the focus and limitations of
      previous and current studies are discussed to present important unanswered
      questions and potential future directions. 

PMID- 25620275
TI  - Association of the immature platelet fraction with sepsis diagnosis and severity.
AB  - Management of Sepsis would greatly benefit from the incorporation of simple and
      informative new biomarkers in clinical practice. Ideally, a sepsis biomarker
      should segregate infected from non-infected patients, provide information about
      prognosis and organ-specific damage, and be accessible to most healthcare
      services. The immature platelet fraction (IPF) and immature reticulocyte fraction
      (IRF) are new analytical parameters of the complete blood count, that have been
      studied as biomarkers of several inflammatory conditions. Recently, a study
      performed in critically-ill patients suggested that IPF could be a more accurate
      sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this
      retrospective study we evaluated the performance of IPF and IRF as biomarkers of
      sepsis diagnosis and severity. 41 patients admitted to two intensive care units
      were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non
      complicated sepsis. Significantly higher IPF levels were observed in patients
      with severe sepsis/septic shock. IPF correlated with sepsis severity scores and
      presented the highest diagnostic accuracy for the presence of sepsis of all
      studied clinical and laboratory parameters. No significant differences were
      observed in IRF levels. Our results suggest that IPF levels could be used as a
      biomarker of sepsis diagnosis and severity. 

PMID- 25620274
TI  - Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing
      pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in
      male rats.
AB  - The present study compared two putative pharmacotherapies for alcohol abuse and
      dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and
      Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate.
      Experiment 1 assessed the effects of different doses of DHEA, pregnanolone,
      naltrexone, and acamprosate on both ethanol- and food-maintained responding under
      a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2
      assessed the effects of different mean intervals of food presentation on
      responding for ethanol under a FR-10 variable-interval (VI) schedule, whereas
      Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI
      80 schedule. In Experiment 1, all four drugs dose-dependently decreased response
      rate for both food and ethanol, although differences in the rate-decreasing
      effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol
      maintained responding more potently than food-maintained responding, whereas the
      reverse was true for naltrexone. Acamprosate decreased responding for both
      reinforcers with equal potency. In Experiment 2, different mean intervals of food
      presentation significantly affected the number of food reinforcers obtained per
      session; however, changes in the number of food reinforcements did not
      significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in
      Experiment 3, only naltrexone significantly decreased both the dose of alcohol
      presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had
      no significant effects on any of the dependent measures, whereas DHEA
      significantly decreased BEC, but did not significantly decrease response rate or
      the dose presented. In summary, DHEA and pregnanolone decreased ethanol
      maintained responding more potently than food-maintained responding under a
      multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol
      self-administration than either naltrexone or acamprosate under that schedule.
      Experiment 2 showed that ethanol intake was relatively independent of the
      interval of reinforcement in the food-maintained component, and Experiment 3
      showed that naltrexone was the most effective drug at the doses tested when the
      interval for food reinforcement was low and maintained under a variable-interval
      schedule. 

PMID- 25620276
TI  - Diagnosis and management of type II myocardial infarction: increased demand for a
      limited supply of evidence.
AB  - Type 2 myocardial infarction (type 2 MI) is defined as myocardial necrosis that
      results from an imbalance of myocardial oxygen supply and demand. Although type 2
      MI is highly prevalent and strongly associated with mortality, the
      pathophysiology remains poorly understood. Discrepancies in definitions,
      frequency of screening, diagnostic approaches, and methods of adjudication lead
      to confusion and misclassification. To date, there is no consensus on the
      diagnostic criteria for type 2 MI. No guidelines exist for the optimal management
      of this condition, and further investigation is urgently needed. This review
      explores the existing evidence on the pathophysiology, diagnosis, prognosis, and
      management of type 2 MI. 

PMID- 25620278
TI  - Recent patents on physical, mineral & organic Acid composition of golden
      delicious and red delicious apples (malus*domestica borkh) grown in the west of
      Iran.
AB  - Apple is one of the fruits that has beneficial effects on human healthy diet and
      life. The aim of this study is to determine some physical, mineral and organic
      acids composition of apple cultivars grown in different locations throughout
      Lorestan province. Apple cultivars had been harvested from different locations
      throughout Lorestan province of Iran. Analyses for 3 elements (Iron, Zinc, and
      calcium) were conducted by the flame atomic absorption spectrometry. Phosphorus
      was measured by the UV-Vis spectrophotometer and Sodium and Potassium were
      measured by the flame photometer. Organic acids were determined by Titration
      method using NaOH and phenolphethalein indicator. Weight was measured by scale
      based on 0.1 g and length and diameters were measured by caliper. The mean weight
      of Red Delicious and Golden Delicious apples was 173.7 g and 146.7 g,
      respectively. The amount of iron, zinc, calcium, phosphorus, sodium, and
      potassium for the red variety was 0.24, 0.14, 28, 8.9, 4.7 and 63.8 respectively;
      values for the Golden variety were 0.23, 0.14, 27.9, 8.8, 4.5, and 66.3 mg/100g
      fresh weight, respectively. The amount of ascorbic acid, malic acid, and citric
      acid for Golden delicious was 9.09, 0.27 and 0.28, respectively; for Red
      delicious apples, the amount was 9.47, 0.26 and 0.28 mg/100 g, respectively.
      Acidities for Golden delicious and Red delicious were 3.7 and 4, respectively.
      One hundred gram of apple fruit grown in Lorestan would provide 3% of iron, 1.5%
      of zinc, 2.8% of calcium and 1.4% of potassium requirements. The amount of
      organic acid in apples of Lorestan province was lower than some other countries. 

PMID- 25620277
TI  - Female-specific factors for IHD: across the reproductive lifespan.
AB  - Ischemic heart disease (IHD) is the number one health threat to women in the USA.
      While significant advances in female-specific symptoms and pathophysiology have
      begun to improve mortality rates, a closer look at risk factors across a woman's
      lifespan needs to be explored. This review targets three time frames:
      premenopause, pregnancy, and postmenopause. During premenopause, menstrual cycle
      patterns and estrogen status provide information for IHD risk. Pregnancy
      conditions provide another window of time that potentially contributes to future
      cardiovascular risk. Lastly, there is a rise in IHD events and mortality after
      menopause. Research continues to decipher the impact of estrogen decline at this
      stage and the effect of menopause hormone therapy as they relate to the
      cardiovascular health of menopausal women. 

PMID- 25620279
TI  - Highly efficient aerobic oxidation of alcohols by using less-hindered nitroxyl
      radical/copper catalysis: optimum catalyst combinations and their substrate
      scope.
AB  - The oxidation of alcohols into their corresponding carbonyl compounds is one of
      the most fundamental transformations in organic chemistry. In our recent report,
      2-azaadamantane N-oxyl (AZADO)/copper catalysis promoted the highly
      chemoselective aerobic oxidation of unprotected amino alcohols into amino
      carbonyl compounds. Herein, we investigated the extension of the promising
      AZADO/copper-catalyzed aerobic oxidation of alcohols to other types of alcohol.
      During close optimization of the reaction conditions by using various alcohols,
      we found that the optimum combination of nitroxyl radical, copper salt, and
      solution concentration was dependent on the type of substrate. Various alcohols,
      including highly hindered and heteroatom-rich ones, were efficiently oxidized
      into their corresponding carbonyl compounds under mild conditions with lower
      amounts of the catalysts. 

PMID- 25620280
TI  - Survey of endoparasites in pet guinea pigs in Italy.
AB  - Little information is available on the occurrence of endoparasites in pet guinea
      pigs (Cavia porcellus). The purpose of this study was to evaluate the prevalence
      of intestinal parasites in cavies kept as pets in southern Italy. Fresh fecal
      samples were randomly collected from 60 guinea pigs housed in pet shops or
      privately owned. All fecal samples were processed using the FLOTAC pellet
      technique to identify and count helminthic eggs/larvae and protozoan
      cysts/oocysts. In addition, the specimens were analyzed also by the Remel
      Xpect(r) Giardia/Cryptosporidium immunoassay. Intestinal parasites were detected
      in 19 out of 60 guinea pigs (31.7 %). Paraspidodera uncinata eggs were found in
      13.3 % (8/60) of the rodents examined, Nippostrongylus-like eggs in 10 % (6/60),
      and finally Eimeria caviae oocysts were found in 10 % (6/60) of the animals. In
      one case, both E. caviae oocysts and P. uncinata eggs were found. None of the
      samples was positive for Cryptosporidium or Giardia. To the authors' knowledge,
      this is the first survey of endoparasites in pet guinea pigs in Italy.

PMID- 25620281
TI  - Erratum to: Molecular study of Trypanosoma caninum isolates based on different
      genetic markers.

PMID- 25620282
TI  - Catechin and quercetin attenuate adipose inflammation in fructose-fed rats and
      3T3-L1 adipocytes.
AB  - SCOPE: This study evaluated the capacity of dietary catechin (C), quercetin (Q),
      and the combination of both (CQ), to attenuate adipose inflammation triggered by
      high fructose (HFr) consumption in rats and by tumor necrosis factor alpha (TNF
      alpha) in 3T3-L1 adipocytes. METHODS AND RESULTS: In rats, HFr consumption for 6
      wk caused dyslipidemia, insulin resistance, reduced plasma adiponectin,
      adiposity, and adipose tissue inflammation. Dietary supplementation with 20
      mg/kg/day of C, Q, and CQ improved all these parameters. In 3T3-L1 adipocytes, C
      and Q attenuated TNF-alpha-induced elevated protein carbonyls, increased
      proinflammatory cytokine expression (MCP-1, resistin), and decreased adiponectin.
      The protective effects of C and Q on adipose inflammation are in part associated
      with their capacity to (i) decrease the activation of the mitogen-activated
      kinases (MAPKs) JNK and p38; and (ii) prevent the downregulation of PPAR-gamma.
      In summary, C and Q, and to a larger extent the combination of both, attenuated
      adipose proinflammatory signaling cascades and regulated the balance of molecules
      that improve (adiponectin) or impair (TNF-alpha, MCP-1, resistin) insulin
      sensitivity. CONCLUSION: Together, these findings suggest that dietary Q and C
      may have potential benefits in mitigating MetS-associated adipose inflammation,
      oxidative stress, and insulin resistance.

PMID- 25620284
TI  - Happy new year.

PMID- 25620286
TI  - Reliability of single and paired-pulse transcranial magnetic stimulation in the
      vastus lateralis muscle.
AB  - INTRODUCTION: Transcranial magnetic stimulation (TMS) is an important tool to
      examine neurological pathologies, movement disorders, and central nervous system
      responses to exercise, fatigue, and training. The reliability has not been
      examined in a functional locomotor knee extensor muscle. METHODS: Within- (n =
      10) and between-day (n = 16) reliability of single and paired-paired pulse TMS
      was examined from the active vastus lateralis. RESULTS: Motor evoked potential
      amplitude and cortical silent period duration showed good within- and between-day
      reliability (intraclass correlation coefficient [ICC] >= 0.82). Short- and long
      interval intracortical inhibition (SICI and LICI, respectively) demonstrated good
      within-day reliability (ICC >= 0.84). SICI had moderate to good between-day
      reliability (ICC >= 0.67), but LICI was not repeatable (ICC = 0.47).
      Intracortical facilitation showed moderate to good within-day reliability (ICC >=
      0.73) but poor to moderate reliability between days (ICC >= 0.51). CONCLUSIONS:
      TMS can reliably assess cortical function in a knee extensor muscle. This may be
      useful to examine neurological disorders that affect locomotion.

PMID- 25620285
TI  - [Avoidance of complications in oncological surgery of the pelvic region :
      combined oncosurgical and plastic reconstruction measures].
AB  - Prevention of perioperative and postoperative complications resulting from
      surgical oncology in the pelvic region remains a major interdisciplinary
      challenge. With modern interdisciplinary concepts joining forces of various
      surgical specialties, tumor resection can be sufficiently carried out with wide
      margins and the patients benefit from reduced morbidity even in complex
      situations. As an example chronic fistulation and secretion from the presacral
      cavity and sinus may result as potential sequelae from intra-abdominal and
      intrapelvic tumor resection, especially when neoadjuvant multimodal therapies
      have been applied. This can be prevented by simultaneous transplantation of for
      example transpelvic vertical rectus abdominis myocutaneous (VRAM) flap transfer,
      while extensive perineal skin and soft tissue defects may also be simultaneously
      reconstructed. In cases of malignant soft tissue tumors in the pelvic region a
      staged surgical procedure can be performed with a period of time between tumor
      resection and reconstruction. Thus, a histological R0 status can be secured prior
      to plastic reconstruction surgery in order to increase oncological safety. In
      cases of postresectional exposition of e. g. pelvic or femoral vessels or
      intrapelvic and intra-abdominal organs simultaneous flap procedure is
      mandatory.The reconstructive armamentarium of the plastic surgeon should contain
      not only pedicled but also free microsurgical flaps so that no compromise in
      terms of the extent of the oncological resection has to be accepted. At the same
      time perioperative and postoperative complications may be avoided and the patient
      quality of life can be preserved even in more complex cases. 

PMID- 25620287
TI  - Preparation of a hybrid monolithic stationary phase with allylsulfonate for the
      rapid and simultaneous separation of cations in capillary ion chromatography.
AB  - A hybrid monolithic column with sulfonate functionality was successfully prepared
      for the simultaneous separation of common inorganic cations in ion-exchange
      chromatographic mode through a simple and easy single-step preparation method.
      The strong cation-exchange moieties were provided directly from allylsulfonate,
      which worked as an organic monomer in the single-step reaction. Inorganic cations
      (Li(+), Na(+), K(+), NH4(+), Cs(+), Rb(+), Mg(2+), Ca(2+), and Sr(2+)) were
      separated satisfactorily by using CuSO4 as the eluent with indirect UV detection.
      The allysulfonate hybrid monolith showed a better performance in terms of speed
      and pressure drop than the capillary packed column. The number of theoretical
      plates achieved was 19,017 plates/m (in the case of NH4(+) as the analyte). The
      relative standard deviations (n = 6) of both retention time and peak height were
      less than 1.96% for all the analyte cations. The allysulfonate hybrid monolithic
      column was successfully applied for the rapid and simultaneous separation of
      inorganic cations in groundwater and the effluent of onsite domestic wastewater
      treatment system.

PMID- 25620288
TI  - Atypical sensory processing is common in extremely low gestational age children.
AB  - AIM: Atypical sensory processing is common in children born extremely
      prematurely. We investigated sensory processing abilities in extremely low
      gestational age (ELGA) children and analysed associated neonatal risk factors,
      neuroanatomical findings and neurodevelopmental outcome. METHODS: We carried out
      a prospective study of 44 ELGA children, including 42 who had undergone brain
      magnetic resonance imaging (MRI) at term-equivalent age, when they were 2 years
      of corrected age. Their sensory processing abilities were assessed with the
      Infant/Toddler Sensory Profile questionnaire and their neurodevelopmental with a
      structured Hempel neurological examination, Griffiths Mental Developmental Scales
      and Bayley Scales of Infant and Toddler Development Third Edition. RESULTS:
      Sensory profiles were definitely or probably atypical (<-1 SD) in half of the
      ELGA children, and the most common behavioural pattern was low registration
      (23%). Sensation seeking was associated with abnormalities in grey and/or white
      matter in the brain MRI (p < 0.01). Atypical oral sensory processing was
      associated with surgical closure of the patent ductus arteriosus (p = 0.02,
      adjusted p < 0.01). CONCLUSION: Atypical sensory processing in ELGA children was
      common, and children with neonatal neuroanatomical lesions tended to present
      specific behavioural responses to sensory stimuli. Surgical closure of the patent
      ductus arteriosus may predispose infants to feeding problems due to atypical oral
      sensory processing.

PMID- 25620289
TI  - The allele T of rs10852936 confers risk for early-onset psoriasis.

PMID- 25620290
TI  - Assessing readiness for self-directed learning within a non-traditional nursing
      cohort.
AB  - Increasing deregulation of the Australian tertiary system has led to changes in
      entry behaviours anticipated in non-traditional student cohorts. Many nursing
      students are returning to formal studies later in their lives seeking a career
      change. Accessibility and flexible study paths make external study increasingly
      attractive. However external studies require a level of commitment and
      willingness to develop self-direction and a capacity for resilience. This study
      sought to elicit the level of self-directed learning readiness (SDLR) among
      undergraduate nursing students currently enrolled at a bachelor level, and to
      elicit what differences existed in the levels of SDLR in relation to age, gender,
      academic year, and previous qualifications. An online survey questionnaire was
      utilised based on the Self-directed Learning Readiness Scale for Nursing
      Education. In contrast to earlier work, the participant profile in this study was
      predominantly non-traditional and captured participants from all three years of
      the nursing programme. Results found no significant age or gender differences.
      First year students demonstrated lower levels of self-directed learning
      readiness. However, unexpected results were demonstrated in the survey subscales
      in relation to previous qualifications. Participants who already held post
      graduate qualifications showed lower scores for Self-Management than those who
      held diploma qualifications, while students who already held a bachelor's degree
      had the highest scores in Desire for Learning. The study findings suggest that
      universities should not assume that SDL capability is dependent on mature age or
      length of exposure to tertiary study. 

PMID- 25620291
TI  - What predicts nurse faculty members' intent to stay in the academic organization?
      A structural equation model of a national survey of nursing faculty.
AB  - OBJECTIVE: To investigate the relations among several factors regarding the
      academic context within a nationally representative sample of U.S. nursing
      faculty. DESIGN: Correlational design using structural equation modeling to
      explore the predictive nature of several factors related to the academic
      organization and the work life of nursing faculty. SETTING: A survey was used to
      evaluate several aspects of the work life of U.S. nursing faculty members.
      PARTICIPANTS: Nursing faculty members in academic organizations across the U.S.
      serving at either CCNE- or NLNAC-accredited institutions of higher education.
      METHODS: Standard confirmatory factor analysis was used to assess the validity of
      a proposed measurement model, and structural equation modeling was used to
      evaluate the validity of a structural/latent variable model. RESULTS: Several
      direct and indirect effects were observed among the factors under investigation.
      Of special importance, perceptions of nurse administration's support and
      perceived teaching expertise positively predicted U.S. nursing faculty members'
      intent to stay in the academic organization. CONCLUSIONS: Understanding the way
      that nursing faculty members' perceptions of the various factors common to the
      academic context interact with intent to stay in the academic organization is
      essential for faculty and nursing administrators. This information can assist
      administrators in obtaining more resources for faculty development to lobby for
      additional faculty in order to meet the teaching, research, and service missions
      of the organization; and to personalize relationships with individual faculty
      members to understand their needs and acknowledge their efforts.

PMID- 25620292
TI  - Arthropods affecting the human eye.
AB  - Ocular infestations by arthropods consist in the parasitization of the human eye,
      either directly (e.g., some insect larvae causing ophthalmomyiasis) or via
      arthropods feeding on lachrymal/conjunctival secretions (e.g., some eye-seeking
      insects, which also act as vectors of eye pathogens). In addition, demodicosis
      and phthiriasis may also cause eye discomfort in humans. Ophthalmomyiasis by
      larvae of the families Oestridae, Calliphoridae and Sarcophagidae, are frequent
      causative agents of human ocular infestations. Over the last decades, the
      extensive use of macrocyclic lactones in cattle has reduced the frequency of
      infestations by Hypoderma bovis and Hypoderma lineatum (family Oestridae), and
      consequently, human infestations by these species. A prompt diagnosis of ocular
      myiasis (e.g., by serological tests) is pivotal for positive prognoses,
      particularly when the larvae are not detectable during the ophthalmologic
      examination. Molecular diagnoses may also assist physicians and parasitologists
      in achieving time-efficient diagnoses of infestations by Oestridae causing
      myiasis. Finally, due to widespread international travel to exotic destinations,
      cases of myiasis are increasing in non-endemic areas, therefore requiring
      physicians to acquire a profound knowledge of the clinical symptoms linked to
      these infestations to prevent costly, inappropriate treatments or severe
      complications. 

PMID- 25620293
TI  - Canine Leishmania vaccines: still a long way to go.
AB  - Dogs are the main reservoir host for zoonotic visceral leishmaniasis, a sand fly
      borne disease caused by Leishmania infantum. In endemic areas, "susceptible" dogs
      suffer from a severe disease characterized by chronic polymorphic
      viscerocutaneous signs that manifest several months from the exposure, whereas
      "resistant" dogs can remain subclinically infected for years or lifelong. The
      protective immune response to Leishmania is cell-mediated; for visceralizing
      Leishmania species a mixed T helper (Th)1/Th2 response with a dominant Th1
      profile is required for protection. The activation of the adaptive immune system
      in naturally resistant dogs is revealed by parasite-specific lymphoproliferation,
      delayed-type hypersensitivity, the production of interferon-gamma and tumour
      necrosis factor-alpha cytokines, and enhanced macrophage leishmanicidal activity
      via nitric oxide. Hence, an effective canine Leishmania vaccine should induce
      strong and long-lasting Th1-dominated immunity to control both infection
      progression and the parasite transmissibility via the vector. Preclinical
      research in rodent models has evaluated the efficacy of several categories of
      Leishmania antigens including killed parasites, cell purified fractions, parasite
      protein components or subunits, single or multiple chimeric recombinant proteins,
      plasmid DNA and viral particles encoding parasite virulence factors. Promising
      antigen(s)/adjuvant combinations from each of the above categories have also been
      tested in dogs; they mostly resulted in limited or no protection in Phase I-II
      studies (designed to test vaccine safety, immunogenicity and laboratory-induced
      protection) in which vaccinated dogs were challenged by the artificial
      intravenous injection of high-load L. infantum promastigotes. The recombinant A2
      antigen plus saponin conferred about 40% protection against infection by this
      challenge system and has been registered in Brazil as a canine vaccine
      (LeishTec((r))). An increasing number of efficacy studies have privileged the use
      of natural challenge consisting in the long-term exposure of vaccinated dogs in
      endemic settings (Phase III). A 2-year field model including regular assessments
      by a set of standard diagnostic markers useful for an accurate infection staging
      has been developed. Again, most of the vaccines tested by this system, which
      included several antigen categories and adjuvants, failed to protect against
      infection and disease. Only two vaccines, consisting of parasite purified
      fractions with saponin derivative adjuvants, showed to confer significant
      protection against disease and death under natural conditions, and have been
      registered as canine vaccines: FML-QuilA (Leishmune((r))) in Brazil, and LiESP/QA
      21 (CaniLeish((r))) in Europe. 

PMID- 25620294
TI  - First finding of Trichinella pseudospiralis in the Neotropical region.
AB  - Prior to this study, only encapsulated species of Trichinella had been found in
      South America, i.e., T. spiralis and T. patagoniensis. Here we report the
      molecular identification of a non-encapsulated isolate of Trichinella from a
      domestic pig in Argentina. The multiplex PCR technique and the analysis of
      mitochondrial and nuclear DNA sequences revealed that it belongs to T.
      pseudospiralis, which parasitises birds and mammals from Australian, Nearctic,
      and Palaearctic regions. Interestingly, the isolate is closely related to the
      Palaearctic population. This is the first report of a non-encapsulated species of
      Trichinella from the Neotropical region. 

PMID- 25620295
TI  - lambda-Orthogonal pericyclic macromolecular photoligation.
AB  - A photochemical strategy enabling lambda-orthogonal reactions is introduced to
      construct macromolecular architectures and to encode variable functional groups
      with site-selective precision into a single molecule by the choice of wavelength.
      lambda-Orthogonal pericyclic reactions proceed independently of one another by
      the selection of functional groups that absorb light of specific wavelengths. The
      power of the new concept is shown by a one-pot reaction of equimolar quantities
      of maleimide with two polymers carrying different maleimide-reactive endgroups,
      that is, a photoactive diene (photoenol) and a nitrile imine (tetrazole). Under
      selective irradiation at lambda=310-350 nm, any maleimide (or activated ene) end
      capped compound reacts exclusively with the photoenol functional polymer. After
      complete conversion of the photoenol, subsequent irradiation at lambda=270-310 nm
      activates the reaction of the tetrazole group with functional enes. The
      versatility of the approach is shown by lambda-orthogonal click reactions of
      complex maleimides, functional enes, and polymers to the central polymer
      scaffold. 

PMID- 25620296
TI  - Bonds to the homeland: Patterns and determinants of women's transnational travel
      frequency among three immigrant groups in Germany.
AB  - Technology developments have changed immigrants' adaptation patterns in modern
      societies, allowing immigrants to sustain dense, complex connections with
      homeland while adjusting in the host country, a new phenomenon termed
      transnationalism. As empirical studies on immigrant transnationalism are still
      scarce, the purpose of this study was to investigate mean levels and determinants
      of a core component of transnationalism-transnational travel. Hypotheses were
      based on context of exiting homeland, living conditions in Germany and
      demographic and sociocultural variables. Transnational travel behaviour was
      assessed as frequency of return trips in three immigrant groups in Germany:
      ethnic Germans, Russian Jews and Turks. Interviews were conducted with 894 women
      participants from these groups. Results showed substantial transnational travel
      behaviour in all groups with Turks reporting higher levels than ethnic Germans
      and Russian Jews. Interindividual differences in transnational travel within
      groups were also examined. Results indicated similarities (e.g. network size in
      home country related positively to transnational travel frequency in all groups)
      and group-specific associations (e.g. co-ethnic identifying related positively to
      transnational travel frequency among Turks, but negatively for the other groups).
      Our study highlights the need for a new understanding of immigration and
      emphasises the consideration of group-specific mechanisms in transnational travel
      behaviour. 

PMID- 25620297
TI  - Investing in the health and well-being of young adults.
AB  - Contrary to popular perception, young adults-ages approximately 18-26 years-are
      surprisingly unhealthy. They are less healthy than adolescents, and they also
      show a worse health profile than those in their late 20s and 30s. The Affordable
      Care Act provisions to extend coverage for young adults are well known, and some
      states had already been pursuing similar efforts before the Affordable Care Act
      was enacted. These initiatives have resulted in important gains in young adults'
      heath care coverage. However, too little attention has been paid to the care that
      young adults receive once they are in the system. Given young adults' health
      problems, this is a critical omission. The Institute of Medicine and National
      Research Council recently released a report titled Investing in the Health and
      Well-Being of Young Adults. The report concludes that young adulthood is a
      critical developmental period and recommends that young adults ages 18-26 years
      be treated as a distinct subpopulation in policy, planning, programming, and
      research. The report also recommends action in three priority areas to improve
      health care for young adults: improving the transition from pediatric to adult
      medical and behavioral health care, enhancing preventive care for young adults,
      and developing evidence-based practices. 

PMID- 25620298
TI  - State policy and teen childbearing: a review of research studies.
AB  - Teen childbearing is affected by many individual, family, and community factors;
      however, another potential influence is state policy. Rigorous studies of the
      relationship between state policy and teen birth rates are few in number but
      represent a body of knowledge that can inform policy and practice. This article
      reviews research assessing associations between state-level policies and teen
      birth rates, focusing on five policy areas: access to family planning, education,
      sex education, public assistance, and access to abortion services. Overall,
      several studies have found that measures related to access to and use of family
      planning services and contraceptives are related to lower state-level teen birth
      rates. These include adolescent enrollment in clinics, minors' access to
      contraception, conscience laws, family planning expenditures, and Medicaid
      waivers. Other studies, although largely cross-sectional analyses, have concluded
      that policies and practices to expand or improve public education are also
      associated with lower teen birth rates. These include expenditures on education,
      teacher-to-student ratios, and graduation requirements. However, the evidence
      regarding the role of public assistance, abortion access, and sex education
      policies in reducing teen birth rates is mixed and inconclusive. These
      conclusions must be viewed as tentative because of the limited number of rigorous
      studies that examine the relationship between state policy and teen birth rates
      over time. Many specific policies have only been analyzed by a single study, and
      few findings are based on recent data. As such, more research is needed to
      strengthen our understanding of the role of state policies in teen birth rates. 

PMID- 25620299
TI  - Twitter chatter about marijuana.
AB  - PURPOSE: We sought to examine the sentiment and themes of marijuana-related
      chatter on Twitter sent by influential Twitter users and to describe the
      demographics of these Twitter users. METHODS: We assessed the sentiment and
      themes of a random sample (n = 7,000) of influential marijuana-related tweets
      (sent from February 5, 20114, to March 5, 2014). Demographics of the users
      tweeting about marijuana were inferred using a social media analytics company
      (Demographics Pro for Twitter). RESULTS: Most marijuana-related tweets reflected
      a positive sentiment toward marijuana use, with pro-marijuana tweets outnumbering
      anti-marijuana tweets by a factor of greater than 15. The most common theme of
      pro-marijuana tweets included the Tweeter stating that he/she wants/plans to use
      marijuana, followed by tweeting about frequent/heavy/or regular marijuana use,
      and that marijuana has health benefits and/or should be legalized. Tweeters of
      marijuana-related content were younger and a greater proportion was African
      American compared with the Twitter average. CONCLUSIONS: Marijuana Twitter
      chatter sent by influential Twitter users tends to be pro-marijuana and popular
      among African-Americans and youth/young adults. Marijuana-related harms may
      afflict some individuals; therefore, our findings should be used to inform online
      and offline prevention efforts that work to target individuals who are most at
      risk for harms associated with marijuana use.

PMID- 25620300
TI  - The mediating role of deviant peers on the link between depressed mood and
      harmful drinking.
AB  - PURPOSE: One's peer group can have a strong impact on depressed mood and harmful
      drinking in adolescence. It remains unclear whether affiliation with deviant
      peers explains the link between these traits. Our study aims to (1) explore the
      developmental relationship between harmful drinking and depressed mood in
      adolescence and (2) establish to which extent affiliation with deviant peers
      explains this relationship. METHODS: A total of 4,863 adolescents from the Avon
      Longitudinal Study of Parents and Children were assessed between the ages of 14
      and 16 years. Harmful drinking was established using age-appropriate measures:
      the Semi-Structured Assessment for the Genetics of Alcoholism in mid-adolescence
      (age, 14 years) and the Alcohol Use Disorders Identification Test in late
      adolescence (age, 16 years). Depressed mood was measured by the Short Mood and
      Feelings Questionnaire at both ages. Affiliation with deviant peers was assessed
      at the age of 15 years. RESULTS: Harmful drinking at the age of 14 years
      predicted depressed mood 2 years later. This association was explained by
      affiliation with deviant peers and remained present even after adjustment for
      earlier depressed mood. Depressed mood at the age of 14 years predicted harmful
      drinking at the age of 16 years via affiliation with deviant peers; however, this
      indirect effect disappeared when adjusting for adolescents' earlier harmful
      alcohol use (age, 14 years). No gender differences were observed. CONCLUSIONS:
      Adolescents who engage in early harmful drinking and subsequently become
      affiliated with a deviant peer group may be at particular risk of later depressed
      mood.

PMID- 25620301
TI  - Gender-based violence against adolescent and young adult women in low- and middle
      income countries.
AB  - PURPOSE: Gender-based violence (GBV) is a global health and human rights issue
      with individual and social determinants. Youth are considered high risk; national
      influences include norms, policies and practices. By age, nation, and region, we
      contrast key GBV indicators, specifically intimate partner violence (IPV) and
      forced sexual debut among adolescent and young adult women using Demographic and
      Health Surveys across low- and middle-income countries. METHODS: National
      prevalence estimates were generated among adolescents (15-19 years) and young
      adults (20-24 years) for lifetime and the past-year physical and sexual IPV among
      ever-married/cohabitating women (30 nations) and forced sexual debut among
      sexually experienced women (17 nations). Meta-analyses provided regional
      estimates and cross-national comparisons, and compared the past-year IPV
      prevalence among adolescent and young adult women to adult women. RESULTS: An
      estimated 28% of adolescent and 29% of young adult women reported lifetime
      physical or sexual IPV, most prevalent in the East and Southern Africa region.
      Regional and cross-national variation emerged in patterns of violence by age;
      overall, young adult women demonstrated higher risk for the past-year IPV
      relative to adult women (meta-analysis odds ratio, 1.20; 95% confidence interval,
      1.10-1.37) and adolescents had a comparable risk (meta-analysis odds ratio, 1.07;
      95% confidence interval, .91-1.23). Forced sexual debut was estimated at 12%
      overall, highest in the East and Southern Africa region. CONCLUSIONS: GBV is
      pervasive among adolescent and young adult women in low- and middle-income
      countries. The unique risk to youth varies across nations, suggesting an age
      place interaction. Future research is needed to clarify contextual determinants
      of GBV. Findings provide direction for integrating youth within GBV prevention
      efforts.

PMID- 25620302
TI  - Childhood abuse and early menarche among Peruvian women.
AB  - PURPOSE: Childhood abuse has been associated with age of menarche in some
      studies, but not all, and few have assessed the independent associations of
      sexual and physical abuse with early menarche. We examined the association
      between childhood abuse and early menarche among pregnant women in Lima, Peru.
      METHODS: Multinomial logistic regression procedures were used to estimate odds
      ratios (OR) and 95% confidence intervals (CIs) for early menarche (<=11 years) in
      relation to any physical or sexual childhood abuse, physical abuse only, sexual
      abuse only, and both physical and sexual abuse in a cohort of 1,499 pregnant
      (first trimester) women. RESULTS: Approximately 69% of participants reported
      experiencing physical or sexual abuse in childhood. The frequencies of physical
      abuse only, sexual abuse only, and both physical and sexual abuse were 37.4%,
      7.7%, and 24.5%, respectively. Compared with women who reported no childhood
      abuse, those who reported any childhood abuse had a 1.38-fold increased odds of
      early menarche (95% CI, 1.01-1.87). Compared with no abuse, the odds of early
      menarche was 1.60-fold among women with childhood sexual abuse only (OR, 1.60;
      95% CI, .93-2.74) and 1.56-fold for those with both physical and sexual abuse
      (OR, 1.56; 95% CI, 1.07-2.25) during childhood. Isolated physical abuse was
      weakly associated with early menarche (OR, 1.23; 95% CI, .87-1.74). There was no
      clear evidence of association of childhood abuse with late menarche (>=15 years).
      CONCLUSIONS: Childhood abuse, particularly joint physical and sexual abuse, is
      associated with early menarche. Our findings add to an expanding body of studies
      documenting the enduring adverse health consequences of childhood abuse.

PMID- 25620303
TI  - Adolescents' media exposure may increase their cyberbullying behavior: a
      longitudinal study.
AB  - PURPOSE: The aim of this study was to examine the effect of adolescents' exposure
      to media portraying antisocial and risk behavior on cyberbullying behavior over
      time. Previous research established relatively high prevalence of cyberbullying
      behavior among adolescents, although not much is known about the possible
      predictors of cyberbullying behavior. This study examines the long-term effects
      of media exposure herein. Furthermore, we examined whether boys and girls differ
      in this respect. METHODS: The long-term effects were tested in a longitudinal
      design with three waves (N = 1,005; age range, 11-17 years; 49% boys). Measured
      variables: cyberbullying behavior and exposure to media with antisocial and risk
      behavior content. RESULTS: Results of mixed-model analyses showed that higher
      levels of exposure to media with antisocial and risk behavior content
      significantly contributed to higher initial rates of cyberbullying behavior.
      Moreover, an increase in exposure to antisocial media content was significantly
      related to an increase in cyberbullying behavior over time. For both boys and
      girls, higher exposure to antisocial and risk behavior media content increases
      cyberbullying behavior over time though more clearly for boys than for girls.
      CONCLUSIONS: This study provided empirical support for the amplifying effect of
      exposure to antisocial media content on adolescents' cyberbullying behavior over
      time. Results are discussed in view of adolescents' media use and the larger
      theoretical framework.

PMID- 25620304
TI  - Predictors of intuitive eating in adolescent girls.
AB  - PURPOSE: To examine proposed predictors of intuitive eating, including social
      appearance comparison, and to test a modified acceptance model of intuitive
      eating in adolescent girls. METHODS: Participants were 400 adolescent girls aged
      12-16 years who completed measures of body acceptance by others, self
      objectification, social appearance comparison, body appreciation, and intuitive
      eating. RESULTS: Correlations showed that all proposed predictors were related to
      intuitive eating in the expected direction. In particular, social appearance
      comparison was negatively related to body appreciation and intuitive eating.
      After controlling for other predictors, social appearance comparison was shown to
      explain unique variance in intuitive eating. Using structural equation modeling,
      an integrated modified acceptance model of intuitive eating yielded an overall
      good fit to the data. Mediation analyses showed that there was a significant
      indirect effect of body acceptance by others on both body appreciation and
      intuitive eating through social appearance comparison and self-objectification.
      CONCLUSIONS: The findings extend the acceptance model of intuitive eating to
      adolescent girls but also identify social comparison as an important mechanism in
      this process. Practically, the findings highlight several areas that may be
      targeted to foster adaptive eating patterns in girls.

PMID- 25620305
TI  - The relationship between developmental assets and food security in adolescents
      from a low-income community.
AB  - PURPOSE: To explore the association between developmental assets
      (characteristics, experiences, and relationships that shape healthy development)
      and food insecurity among adolescents from a low-income urban community. METHODS:
      This mixed-methods study occurred in two phases. In phase 1, using a census
      approach, 2,350 6th to 12th graders from the public school district completed an
      anonymous survey that included the developmental assets profile (DAP), the youth
      self-report form of the Core Food Security Module, and demographic questions.
      Logistic and multinomial regression analyses determined independent associations
      between developmental assets and food security adjusting for demographics. In
      phase 2, 20 adult key informant interviews and four semistructured student focus
      groups were performed to explain findings from phase 1. RESULTS: On average, DAP
      scores were consistent with national norms. Food insecurity was prevalent; 14.9%
      reported low food security and 8.6% very low food security (VLFS). Logistic
      regression revealed that higher DAP was associated with lower odds of food
      insecurity (odds ratio [OR], .96; 95% confidence interval [CI], .95-.97); family
      assets drove this association (OR, .93; 95% CI, .91-.95). In multinomial
      regression modeling, these associations persisted, and paradoxically, higher
      community assets were also associated with VLFS (ORVLFS, 1.08; 95% CI, 1.04
      1.13). Qualitative analyses suggested that greater need among VLFS youth led to
      increased connections to community resources despite barriers to access such as
      stigma, home instability, and cultural differences. CONCLUSION: Food insecurity
      is a pervasive problem among adolescents from low-income communities and is
      associated with lower developmental assets, particularly family assets. The fact
      that community assets were higher among VLFS youth underscores the importance of
      community-level resources in struggling areas.

PMID- 25620306
TI  - Adolescent pregnancy, birth, and abortion rates across countries: levels and
      recent trends.
AB  - PURPOSE: To examine pregnancy rates and outcomes (births and abortions) among 15-
      to 19-year olds and 10- to 14-year olds in all countries for which recent
      information could be obtained and to examine trends since the mid-1990s. METHODS:
      Information was obtained from countries' vital statistics reports and the United
      Nations Statistics Division for most countries in this study. Alternate sources
      of information were used if needed and available. We present estimates primarily
      for 2011 and compare them to estimates published for the mid-1990s. RESULTS:
      Among the 21 countries with complete statistics, the pregnancy rate among 15- to
      19-year olds was the highest in the United States (57 pregnancies per 1,000
      females) and the lowest rate was in Switzerland (8). Rates were higher in some
      former Soviet countries with incomplete statistics; they were the highest in
      Mexico and Sub-Saharan African countries with available information. Among
      countries with reliable evidence, the highest rate among 10- to 14-year olds was
      in Hungary. The proportion of teen pregnancies that ended in abortion ranged from
      17% in Slovakia to 69% in Sweden. The proportion of pregnancies that ended in
      live births tended to be higher in countries with high teen pregnancy rates (p =
      .02). The pregnancy rate has declined since the mid-1990s in the majority of the
      16 countries where trends could be assessed. CONCLUSIONS: Despite recent
      declines, teen pregnancy rates remain high in many countries. Research on the
      planning status of these pregnancies and on factors that determine how teens
      resolve their pregnancies could further inform programs and policies.

PMID- 25620307
TI  - Influence of family and school-level factors on age of sexual initiation.
AB  - PURPOSE: This study examined the association of individual, family, and school
      level characteristics with age of sexual initiation (ASI) and focused
      specifically on school context as a moderator of known predictors of ASI.
      METHODS: Data are from Waves I and IV of the National Longitudinal Study of
      Adolescent Health (N = 10,596). Predictors include grade point average, physical
      development, attitudes about sex, likelihood of higher education, alcohol use,
      delinquency, family structure, parents' education level, childhood abuse,
      maternal approval of sex, parental monitoring, and parent-child relationship
      quality. School-level predictors are averages of adolescents' attitudes about sex
      and likelihood of higher education and parents' education. Hierarchical linear
      models run separately by sex were used to predict ASI. RESULTS: When school-level
      attitudes about sex are more favorable, both boys and girls report younger ASI,
      and school mean parental education attainment moderates the influence of
      individual adolescents' attitudes about sex on ASI. More of the predictors are
      significant for girls than boys, whereas perception of maternal and peer approval
      of sexual activity are the most salient predictors of younger ASI for boys.
      CONCLUSIONS: Results highlight the importance of school context for understanding
      adolescents' motivations for early ASI. Findings support the need for school-wide
      prevention interventions that engage adolescents, peers, and parents in
      addressing attitudes about early sex.

PMID- 25620308
TI  - Not in Education, Employment, or Training status among young Swiss men.
      Longitudinal associations with mental health and substance use.
AB  - PURPOSE: Not in Education, Employment, or Training (NEET) youth are youth
      disengaged from major social institutions and constitute a worrying concern.
      However, little is known about this subgroup of vulnerable youth. This study
      aimed to examine if NEET youth differ from other contemporaries in terms of
      personality, mental health, and substance use and to provide longitudinal
      examination of NEET status, testing its stability and prospective pathways with
      mental health and substance use. METHODS: As part of the Cohort Study on
      Substance Use Risk Factors, 4,758 young Swiss men in their early 20s answered
      questions concerning their current professional and educational status,
      personality, substance use, and symptomatology related to mental health.
      Descriptive statistics, generalized linear models for cross-sectional
      comparisons, and cross-lagged panel models for longitudinal associations were
      computed. RESULTS: NEET youth were 6.1% at baseline and 7.4% at follow-up with
      1.4% being NEET at both time points. Comparisons between NEET and non-NEET youth
      showed significant differences in substance use and depressive symptoms only.
      Longitudinal associations showed that previous mental health, cannabis use, and
      daily smoking increased the likelihood of being NEET. Reverse causal paths were
      nonsignificant. CONCLUSIONS: NEET status seemed to be unlikely and transient
      among young Swiss men, associated with differences in mental health and substance
      use but not in personality. Causal paths presented NEET status as a consequence
      of mental health and substance use rather than a cause. Additionally, this study
      confirmed that cannabis use and daily smoking are public health problems.
      Prevention programs need to focus on these vulnerable youth to avoid them being
      disengaged.

PMID- 25620309
TI  - Daily concordance between parent and adolescent sleep habits.
AB  - PURPOSE: To assess the daily concordance between parent and adolescent daily
      sleep habits, how that concordance compares to other predictors of sleep, and
      whether the degree of concordance varies across families. METHODS: A total of 421
      adolescents (Mage = 15.03 years) and their primary caregivers (Mage = 41.93
      years) reported their sleep, bed, and wake times on a daily basis for a 2-week
      period. Approximately 80% of the sample repeated the same protocol 1 year later.
      RESULTS: Multilevel modeling indicated a significant concordance between parent
      and adolescent sleep, bed, and wake times on a daily basis. Concordance existed
      independent of other predictors of sleep such as day of the week and adolescent
      study time. Larger families and those with higher levels of parent-adolescent
      support exhibited greater concordance. CONCLUSIONS: Adolescent sleep is connected
      to the sleep habits of their parents, above and beyond commonly known structural
      and experiential factors that can shape teenage sleep. Efforts to improve teenage
      sleep should pay greater attention to the sleep patterns of parents and
      potentially other family members.

PMID- 25620310
TI  - Health care providers' comfort with and barriers to care of transgender youth.
AB  - PURPOSE: To explore providers' clinical experiences, comfort, and confidence with
      and barriers to providing care to transgender youth. METHODS: An online survey
      was administered to members of the Society for Adolescent Health and Medicine and
      the Pediatric Endocrine Society with items querying about clinical exposure to
      transgender youth, familiarity with and adherence to existing clinical practice
      guidelines, perceived barriers to providing transgender-related care, and comfort
      and confidence with providing transgender-related care. The response rate was
      21.9% (n = 475). RESULTS: Of the respondents, 66.5% had provided care to
      transgender youth, 62.4% felt comfortable with providing transgender medical
      therapy, and 47.1% felt confident in doing so. Principal barriers to provision of
      transgender-related care were lack of the following: training, exposure to
      transgender patients, available qualified mental health providers, and insurance
      reimbursement. CONCLUSIONS: This study suggests that more training in transgender
      related care, available qualified mental health providers, and insurance
      reimbursement for transgender-related care are needed.

PMID- 25620311
TI  - Further thoughts on starting antiretroviral therapy: a response to ball.

PMID- 25620312
TI  - MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells
      and its reduction causes CCL4 increase with age.
AB  - Chemokines play a pivotal role in regulating the immune response through a
      tightly controlled expression. Elevated levels of inflammatory chemokines
      commonly occur with aging but the mechanism underlying this age-associated change
      is not fully understood. Here, we report the role of microRNA-125b (miR-125b) in
      regulating inflammatory CC chemokine 4 (CCL4) expression in human immune cells
      and its altered expression with aging. We first analyzed the mRNA level of CCL4
      in eight different types of immune cells including CD4 and CD8 T-cell subsets
      (naive, central and effector memory), B cells and monocytes in blood from both
      young (<=42 years) and old (>=70 years) adults. We observed that monocytes and
      naive CD8 T cells expressed higher levels of CCL4 and exhibited an age-related
      increase in CCL4. We then found the level of miR-125b was inversely correlated
      with the level of CCL4 in these cells, and the level of miR-125b was reduced in
      monocytes and naive CD8 T cells of the old compared to the young adults. Knock
      down of miR-125b by shRNA in monocytes and naive CD8 T cells led to an increase
      of CCL4 protein, whereas enhanced miR-125b expression by transfection in naive
      CD8 T cells resulted in a reduction of the CCL4 mRNA and protein in response to
      stimulation. Finally, we demonstrated that miR-125b action requires the 'seed'
      sequence in 3'UTR of CCL4. Together these findings demonstrated that miR-125b is
      a negative regulator of CCL4 and its reduction is partially responsible for the
      age-related increase of CCL4. 

PMID- 25620313
TI  - Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing
      loss: a randomized clinical trial.
AB  - Despite a robust hearing conservation program, military personnel continue to be
      at high risk for noise induced hearing loss (NIHL). For more than a decade, a
      number of laboratories have investigated the use of antioxidants as a safe and
      effective adjunct to hearing conservation programs. Of the antioxidants that have
      been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL
      in the laboratory, but its clinical efficacy is still controversial. This study
      provides a prospective, randomized, double-blinded, placebo-controlled clinical
      trial investigating the safety profile and the efficacy of NAC to prevent hearing
      loss in a military population after weapons training. Of the 566 total study
      subjects, 277 received NAC while 289 were given placebo. The null hypothesis for
      the rate of STS was not rejected based on the measured results. While no
      significant differences were found for the primary outcome, rate of threshold
      shifts, the right ear threshold shift rate difference did approach significance
      (p = 0.0562). No significant difference was found in the second primary outcome,
      percentage of subjects experiencing an adverse event between placebo and NAC
      groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary
      outcome, STS rate in the trigger hand ear, did show a significant difference
      (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288).
      Additionally, post-hoc analysis showed significant differences in threshold shift
      rates when handedness was taken into account. While the secondary outcomes and
      post-hoc analysis suggest that NAC treatment is superior to the placebo, the
      present study design failed to confirm this. The lack of significant differences
      in overall hearing loss between the treatment and placebo groups may be due to a
      number of factors, including suboptimal dosing, premature post-exposure
      audiograms, or differences in risk between ears or subjects. Based on secondary
      outcomes and post hoc analyses however, further studies seem warranted and are
      needed to clarify dose response and the factors that may have played a role in
      the observed results. 

PMID- 25620314
TI  - The verbal transformation effect and the perceptual organization of speech:
      influence of formant transitions and F0-contour continuity.
AB  - This study explored the role of formant transitions and F0-contour continuity in
      binding together speech sounds into a coherent stream. Listening to a repeating
      recorded word produces verbal transformations to different forms; stream
      segregation contributes to this effect and so it can be used to measure changes
      in perceptual coherence. In experiment 1, monosyllables with strong formant
      transitions between the initial consonant and following vowel were monotonized;
      each monosyllable was paired with a weak-transitions counterpart. Further stimuli
      were derived by replacing the consonant-vowel transitions with samples from
      adjacent steady portions. Each stimulus was concatenated into a 3-min-long
      sequence. Listeners only reported more forms in the transitions-removed condition
      for strong-transitions words, for which formant-frequency discontinuities were
      substantial. In experiment 2, the F0 contour of all-voiced monosyllables was
      shaped to follow a rising or falling pattern, spanning one octave. Consecutive
      tokens either had the same contour, giving an abrupt F0 change between each
      token, or alternated, giving a continuous contour. Discontinuous sequences caused
      more transformations and forms, and shorter times to the first transformation.
      Overall, these findings support the notion that continuity cues provided by
      formant transitions and the F0 contour play an important role in maintaining the
      perceptual coherence of speech. 

PMID- 25620315
TI  - Histamine promotes locomotion recovery after spinal cord hemisection via
      inhibiting astrocytic scar formation.
AB  - AIM: This study investigated whether histamine could play a protective role in
      pathophysiological response of spinal cord injury (SCI) and regulate the glial
      scar formation. METHODS: Functional assessment and histological analyses were
      performed to investigate the effect of histamine after SCI. Histidine
      decarboxylase knockout (HDC(-/-)) mice were used to confirm the action of
      histamine. Selective antagonists for H1 and H2 receptors were utilized in vivo
      and in vitro to verify the functional properties of histamine on astrogliosis.
      RESULTS: The local administration of histamine significantly attenuated the
      tissue damage and glial scar formation after SCI. In particular, the astrogliosis
      and neurocan expression found around the lesion were significantly suppressed by
      histamine. Immunofluorescent staining for neurofilament showed that histamine
      promoted axonal growth across the glial scar. The HDC(-/-) mice, lacking in
      endogenous histamine, showed lower behavior score, increased lesion size and
      astrogliosis, as compared with the wild types. The effect of histamine on
      locomotor recovery and reactive astrogliosis is reversed by H1 receptor
      antagonist but not H2 receptor antagonist. CONCLUSIONS: Our results indicate that
      histamine significantly improved the chronic locomotor recovery via attenuating
      astrogliosis after SCI by stimulating histamine H1 receptor. This study
      highlights a therapeutic potential of histamine and its related drugs for SCI.

PMID- 25620316
TI  - Effects of repeated bouts of long-duration endurance exercise on muscle and
      urinary levels of 8-hydroxy-2'-deoxyguanosine in moderately trained cyclists.
AB  - The purpose of this study was to determine the effects of repeated bouts of long
      duration endurance exercise on both muscle and urinary levels of oxidative DNA
      damage in moderately trained individuals. Seven moderately trained male cyclists
      participated in this study. All participants repeated two sessions consisting of
      a 5-h cycling period (equivalent to approximately 52%[Formula: see text]O2peak)
      followed by a 15-h rest, then a 40-km time trial. During the sessions,
      participants were instructed to take water ad libitum and to consume a standard
      sports drink consisting of 0.12 g.kg(-1) body weight.hr(-1) of carbohydrates. For
      each session, 24 h urine output was collected on the day before the 5-h exercise,
      and also between the 5-h exercise and 40-km time trial, in addition to between
      days 1-5 post-exercise. Subsequently, muscle and urinary levels of 8-hydroxy-2'-
      deoxyguanosine (8-OHdG) were determined using high performance liquid
      chromatography with electrochemical detection. No significant alterations were
      observed between two sessions at the muscle or urinary levels of 8-OHdG. These
      results suggest that repeated bouts of exercise with a 7-day washout period may
      not lead to an accumulation of DNA damage products after a second 5-h stationary
      cycling bout. 

PMID- 25620317
TI  - Atomic force microscopy and Langmuir-Blodgett monolayer technique to assess
      contact lens deposits and human meibum extracts.
AB  - PURPOSE: The purpose of this exploratory study was to investigate the differences
      in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface
      topography between participants with and without meibomian gland dysfunction
      (MGD). METHODS: Meibum study: Meibum was collected from all participants and
      studied via Langmuir-Blodgett (LB) deposition with subsequent Atomic Force
      Microscopy (AFM) visualization and surface roughness analysis. CL Study:
      Participants with and without MGD wore both etafilcon A and balafilcon A CLs in
      two different phases. CL lipid deposits were extracted and analyzed using
      pressure-area isotherms with the LB trough and CL surface topographies and
      roughness values were visualized using AFM. RESULTS: Meibum study: Non-MGD
      participant meibum samples showed larger, circular aggregates with lower surface
      roughness, whereas meibum samples from participants with MGD showed more lipid
      aggregates, greater size variability and higher surface roughness. CL Study: Worn
      CLs from participants with MGD had a few large tear film deposits with lower
      surface roughness, whereas non-MGD participant-worn lenses had many small lens
      deposits with higher surface roughness. Balafilcon A pore depths were shallower
      in MGD participant worn lenses when compared to non-MGD participant lenses.
      Isotherms of CL lipid extracts from MGD and non-MGD participants showed a
      seamless rise in surface pressure as area decreased; however, extracts from the
      two different lens materials produced different isotherms. CONCLUSIONS: MGD and
      non-MGD participant-worn CL deposition were found to differ in type, amount, and
      pattern of lens deposits. Lipids from MGD participants deposited irregularly
      whereas lipids from non-MGD participants showed more uniformity.

PMID- 25620319
TI  - How Israeli social workers perceive adolescent girls in prostitution.
AB  - The phenomenon of girls in prostitution poses great challenges to professionals
      who work with adolescent girls at risk and in distress. Prostitution is socially
      stigmatized and seen as something shameful. However, current theory and research
      show adolescent girls in prostitution to be victims of violence, exploitation and
      trauma. This naturalistic qualitative study examined the views of 15 social
      workers at six Adolescent Girls Treatment Units in Israel on prostitution and on
      adolescent girls in prostitution. Data was collected through in-depth semi
      structured interviews. The participants struggled to link the term "prostitution"
      with the adolescent girls in their care. The findings explore the source this
      perceived conflict, and its manifestation in the participants' professional
      intervention with the girls. The discussion examines the participants'
      professional discourse about adolescent girls in prostitution, and offers
      explanations for their difficulty in associating the adolescent girls in their
      care with prostitution. 

PMID- 25620318
TI  - Validating estimates of prevalence of non-communicable diseases based on
      household surveys: the symptomatic diagnosis study.
AB  - BACKGROUND: Easy-to-collect epidemiological information is critical for the more
      accurate estimation of the prevalence and burden of different non-communicable
      diseases around the world. Current measurement is restricted by limitations in
      existing measurement systems in the developing world and the lack of biometry
      tests for non-communicable diseases. Diagnosis based on self-reported signs and
      symptoms ("Symptomatic Diagnosis," or SD) analyzed with computer-based algorithms
      may be a promising method for collecting timely and reliable information on non
      communicable disease prevalence. The objective of this study was to develop and
      assess the performance of a symptom-based questionnaire to estimate prevalence of
      non-communicable diseases in low-resource areas. METHODS: As part of the
      Population Health Metrics Research Consortium study, we collected 1,379
      questionnaires in Mexico from individuals who suffered from a non-communicable
      disease that had been diagnosed with gold standard diagnostic criteria or
      individuals who did not suffer from any of the 10 target conditions. To make the
      diagnosis of non-communicable diseases, we selected the Tariff method, a
      technique developed for verbal autopsy cause of death calculation. We assessed
      the performance of this instrument and analytical techniques at the individual
      and population levels. RESULTS: The questionnaire revealed that the information
      on health care experience retrieved achieved 66.1% (95% uncertainty interval
      [UI], 65.6-66.5%) chance corrected concordance with true diagnosis of non
      communicable diseases using health care experience and 0.826 (95% UI, 0.818
      0.834) accuracy in its ability to calculate fractions of different causes. SD is
      also capable of outperforming the current estimation techniques for conditions
      estimated by questionnaire-based methods. CONCLUSIONS: SD is a viable method for
      producing estimates of the prevalence of non-communicable diseases in areas with
      low health information infrastructure. This technology can provide higher
      resolution prevalence data, more flexible data collection, and potentially
      individual diagnoses for certain conditions.

PMID- 25620321
TI  - Clinical and ultrasonographic study of patients presenting with transvaginal mesh
      complications.
AB  - AIM: The objective of this study was to investigate the clinical and
      ultrasonographic findings of women who had three-dimensional endovaginal
      ultrasound (EVUS) for the management of vaginal mesh complications. METHODS: This
      was a retrospective study of patients that had EVUS due to mesh complications at
      a tertiary care center. The clinical charts were reviewed. The stored 3D volumes
      were reviewed regarding mesh information by two examiners independently. The
      predictive value of physical examination for detection of vaginal mesh was
      calculated. Patient outcomes were reviewed. RESULTS: Seventy-nine patients
      presented to our center because of their, or their physicians' concern regarding
      mesh complications. Forty-one (51.9%) had vaginal/pelvic pain, and 51/62 (82.2%)
      of sexually active women experienced dyspareunia. According to ultrasonographic
      findings, mesh or sling was not demonstrated in six patients who believed they
      have had mesh/sling implantation. The positive predictive value for vaginal
      examination was 94.5% (95% CI: 84.9%-98.8%), negative predictive value was 12.5%
      (95% CI: 2.8%-32.4%), sensitivity was 72.2% (95% CI: 59.4%-81.2%), and
      specificity was 50.0% (95% CI: 12.4%-87.6%). Fifty-four patients were indicated
      for surgical treatment. Median postoperative review was 12 (range, 3-18) months
      and 38/53 (71.7%) patients were satisfied. CONCLUSIONS: The most common
      complaints of vaginal mesh complications were pain and dyspareunia. EVUS appeared
      to be helpful for assessing mesh presence, location, and extent including
      planning for surgical intervention.

PMID- 25620322
TI  - Dual gold-catalyzed head-to-tail coupling of iodoalkynes.
AB  - Various haloalkynes are converted in the presence of a dual activation gold
      catalyst. Via a dual activation process a completely atom economic head-to-tail
      coupling delivers gem-dihalogenated conjugated enynes as valuable building blocks
      for organic synthesis. 

PMID- 25620323
TI  - Changes in the micro- and nanostructure of siliceous valves in the diatom Synedra
      acus under the effect of colchicine treatment at different stages of the cell
      cycle.
AB  - The important role of the cytoskeleton in the morphogenesis of siliceous frustule
      components, which are synthesized within the diatom cells, has been revealed due
      to experiments with microtubule inhibitors. It has been shown that colchicine
      entering the diatom cell inhibits polymerization of tubulin, the main protein of
      microtubules, thereby disrupting the normal processes of biogenic silica
      deposition and daughter valve morphogenesis. In this study, experiments with a
      synchronized culture of the pennate diatom Synedra acus have been performed to
      determine the timing and duration of the formation of various valve components
      and analyze the effect of colchicine at a subtoxic concentration on the structure
      of daughter valves at different stages of their morphogenesis. Electron
      microscopic analysis has revealed several types of micro- and nanoscale anomalies
      in daughter valve morphology, with their frequency varying depending on the time
      of colchicine treatment. Laser scanning microscopy of preparations vitally
      stained with Tubulin Tracker Green has shown that polymerized tubulin at early
      stages of valve morphogenesis is localized along the periphery of the developing
      valve. This is evidence for an important role of microtubules in the horizontal
      growth of the valve at the stage when its general structural pattern is
      established, including its shape and arrangement of basic micro- and
      nanostructures. Treatment with a microtubule inhibitor at a certain stage of
      valve morphogenesis makes it possible to obtain new forms with a specific
      structure of siliceous components that hold promise for use in nanotechnologies. 

PMID- 25620324
TI  - Determination of acrolein in serum by high-performance liquid chromatography with
      fluorescence detection after pre-column fluorogenic derivatization using 1,2
      diamino-4,5-dimethoxybenzene.
AB  - Acrolein is a major unsaturated aldehyde that is generated during the lipid
      peroxidation process. The measurement of acrolein in biological samples should be
      useful to estimate the degree of lipid peroxidation and to evaluate the effect of
      hazardous properties of acrolein on human health. In this study, a highly
      sensitive and selective high-performance liquid chromatography with fluorescence
      detection method was developed for the determination of acrolein in human serum.
      The proposed method involves the pre-column fluorogenic derivatization of
      acrolein with 1,2-diamino-4,5-dimethoxybenzene (DDB) as a reagent. The
      fluorescent derivative of acrolein could be detected clearly without any
      interfering reagent blank peaks because DDB does not have intrinsic fluorescence
      itself, and the detection limit was 10 nM (signal-to-noise ratio = 3). The
      proposed method could selectively detect acrolein in human serum with a simple
      protein precipitation treatment.

PMID- 25620326
TI  - The role of hemodynamic catheterization in the evaluation of hypertrophic
      obstructive cardiomyopathy: A case series.
AB  - Confirmation of the presence and magnitude of left ventricular outflow tract
      (LVOT) obstruction is a critical component of the evaluation of symptoms in
      patients with hypertrophic cardiomyopathy (HCM). The presence of LVOT obstruction
      in patients with severe symptoms refractory to pharmacologic therapy identifies a
      subgroup of HCM patients who may benefit from septal reduction therapy. Two
      dimensional echocardiography with continuous wave Doppler is the main tool for
      confirming the presence and severity of LVOT obstruction in HCM. However, when
      uncertainty remains following non-invasive evaluation, invasive hemodynamics
      studies are required to confirm and quantify LVOT obstruction. In this manuscript
      we describe a series of 6 cases in which hemodynamic catheterization is
      instrumental in supplementing non-invasive imaging in the assessment of LVOT
      obstruction in HCM.

PMID- 25620325
TI  - Quantifying small molecule phenotypic effects using mitochondrial morpho
      functional fingerprinting and machine learning.
AB  - In primary fibroblasts from Leigh Syndrome (LS) patients, isolated mitochondrial
      complex I deficiency is associated with increased reactive oxygen species levels
      and mitochondrial morpho-functional changes. Empirical evidence suggests these
      aberrations constitute linked therapeutic targets for small chemical molecules.
      However, the latter generally induce multiple subtle effects, meaning that in
      vitro potency analysis or single-parameter high-throughput cell screening are of
      limited use to identify these molecules. We combine automated image
      quantification and artificial intelligence to discriminate between primary
      fibroblasts of a healthy individual and a LS patient based upon their
      mitochondrial morpho-functional phenotype. We then evaluate the effects of newly
      developed Trolox variants in LS patient cells. This revealed that Trolox
      ornithylamide hydrochloride best counterbalanced mitochondrial morpho-functional
      aberrations, effectively scavenged ROS and increased the maximal activity of
      mitochondrial complexes I, IV and citrate synthase. Our results suggest that
      Trolox-derived antioxidants are promising candidates in therapy development for
      human mitochondrial disorders. 

PMID- 25620327
TI  - Decision-analytic modeling studies: An overview for clinicians using multiple
      myeloma as an example.
AB  - PURPOSE: The purpose of this study was to provide a clinician-friendly overview
      of decision-analytic models evaluating different treatment strategies for
      multiple myeloma (MM). METHODS: We performed a systematic literature search to
      identify studies evaluating MM treatment strategies using mathematical decision
      analytic models. We included studies that were published as full-text articles in
      English, and assessed relevant clinical endpoints, and summarized methodological
      characteristics (e.g., modeling approaches, simulation techniques, health
      outcomes, perspectives). RESULTS: Eleven decision-analytic modeling studies met
      our inclusion criteria. Five different modeling approaches were adopted: decision
      tree modeling, Markov state-transition modeling, discrete event simulation,
      partitioned-survival analysis and area-under-the-curve modeling. Health outcomes
      included survival, number-needed-to-treat, life expectancy, and quality-adjusted
      life years. Evaluated treatment strategies included novel agent-based combination
      therapies, stem cell transplantation and supportive measures. CONCLUSION:
      Overall, our review provides a comprehensive summary of modeling studies
      assessing treatment of MM and highlights decision-analytic modeling as an
      important tool for health policy decision making.

PMID- 25620328
TI  - [2014 European Society of Cardiology guidelines on hypertrophic cardiomyopathy].

PMID- 25620329
TI  - ["Cardiac" rehabilitation that cardiologists are not "authorized"].

PMID- 25620330
TI  - The association between coronary atherosclerotic burden and asymmetric
      dimethylarginine, carotis intima media thickness and endothelial function.
AB  - OBJECTIVES: Detection of extent and severity of atherosclerosis using easy, non
      invasive methods is of great importance. Atherosclerotic burden may be evaluated
      with the Gensini scoring system (GSS). Carotis intima media thickness (CIMT),
      plasma asymmetric dimethyl arginine (ADMA) level, and endothelial dysfunction are
      well known surrogate markers of atherosclerosis. The aim of this study was to
      evaluate the relationship between atherosclerotic burden determined by the GSS,
      and ADMA, CIMT and endothelial function. STUDY DESIGN: Consecutive patients who
      had undergone coronary angiography were evaluated. 50 patients with acute
      coronary syndrome (ACS), 50 patients with stable coronary artery disease (SCA),
      and 50 patients with normal coronary arteries (NCA) were included. All subjects'
      GSS, ADMA, CIMT and endothelial functions were evaluated and compared. RESULTS:
      GSS was higher in ACS than SCA (75.4 vs 54.9; p<0.001). CIMT was higher in ACS
      and SCA in compared to NCA (0.98, 0.96, 0.78 mm respectively; p<0.001).
      Endothelium derived vasodilatory response (EDVR) was decreased in ACS and SCA in
      compared to NCA (3.5+/-2.1%, 3.3+/-1.8%, 7.2+/-3.5% respectively; p<0.001).
      Plasma ADMA concentration was higher in ACS and SCA in compared to NCA (0.928,
      0.992, 0.475 umol/l respectively; p<0.001). There was a weak positive correlation
      between GSS and plasma ADMA levels (r=0.293; p=0.002), an intermediate positive
      correlation between GSS and CIMT (r=0.508; p<0.001), and an intermediate negative
      correlations between GSS and EDVR (r= -0.662; p<0.001). CONCLUSION: This study
      showed that CIMT, ADMA concentration and endothelial dysfunction were
      significantly associated with CAD. However, only the GSS was significantly
      different between ACS and SCA groups.

PMID- 25620331
TI  - Does cardiac rehabilitation improve left ventricular diastolic function of
      patients with acute myocardial infarction?
AB  - OBJECTIVES: We aimed to observe the effect of cardiac rehabilitation (CR) on left
      ventricular diastolic function in patients with acute myocardial infarction (AMI)
      and revascularization by percutaneous coronary intervention (PCI). STUDY DESIGN:
      82 patients were enrolled the study; 42 who were participating in a CR program,
      and 40 who did not maintain the program as a control group. Measurements of
      mitral inflow included the peak early filling (E-wave) and late diastolic filling
      (A-wave) velocities, the E/A ratio, deceleration time (DT) of early filling
      velocity and mitral A-wave duration. The early diastolic annular velocity has
      been expressed as e' with PW tissue Doppler imaging. The mitral inflow E velocity
      to tissue Doppler e' (E/e') was calculated and isovolumic relaxation time (IVRT)
      was measured. Measurements of pulmonary venous waveforms included peak systolic
      (S) velocity, peak anterograde diastolic (D) velocity and the time difference
      between the duration of the atrial reversal (Ar) and mitral A-wave duration (Ar
      A). RESULTS: E/A and septal e' were better with the CR group than the control
      group. (p=0.048 vs p=0.006 respectively). The difference between E/e'
      measurements were not statistically significant (p=0.138). The left ventricular
      diastolic function of patients were partially improved with cardiac
      rehabilitation. There was no association between infarct-related artery (IRA) and
      diastolic functional measurements of the left ventricle in the individuals. Only
      hypertension was found significantly associated with E/A (p=0.000). CONCLUSION:
      CR improves septal e' and E/A significantly in patients with AMI and
      revascularized successfully by PCI, especially in those with hypertension.

PMID- 25620332
TI  - [Assessment of right ventricular systolic function in patients with chronic renal
      failure before and after hemodialysis by means of various echocardiographic
      modalities].
AB  - OBJECTIVES: The goal of the study was to determine the effect of decreased
      preload on right ventricular systolic function, as measured by new and old
      echocardiographic parameters in chronic renal failure (CRF) patients. STUDY
      DESIGN: A total of 30 CRF patients (mean age 48+/-15 years, 11 male and 19
      female) undergoing hemodialysis were included in the study. Echocardiography was
      used to determine left ventricular ejection fraction (LVEF), left atrial volume,
      right atrial area, right ventricular end-diastolic area, systolic pulmonary
      artery pressure, right ventricular fractional area change (RV FAC), right
      ventricular myocardial performance index (Tei index), right ventricular tissue
      Doppler S' (RV S') velocity, isovolumic myocardial acceleration (IVA), tricuspid
      annular plane systolic excursion (TAPSE) and right ventricular outflow tract
      systolic excursion (RVOT SE) before and after hemodialysis. RESULTS: The RV S'
      velocity and RVOT SE parameters, which are indicators of right ventricular
      systolic function, did not change significantly after hemodialysis (p=0.919,
      p=0.186). However, the RV FAC, Tei index, IVA and TAPSE values were significantly
      increased (p<0.001 for all). TAPSE was found to be the only parameter that had a
      positive correlation with the amount of fluid removed (p=0.041 and r=0.375).
      CONCLUSION: Although RV S' velocity and RVOT SE, was found to be independent of
      preload, RV FAC, Tei index, IVA and TAPSE values were dependent on preload. In
      addition, TAPSE correlated with the amount of fluid removed.

PMID- 25620333
TI  - [Relationship between presence of fragmented QRS on 12-lead electrocardiogram on
      admission and long-term mortality in patients with non-ST elevated myocardial
      infarction].
AB  - OBJECTIVES: Fragmented QRS (fQRS) as a predictor of cardiac events in coronary
      artery disease has previously been reported. In this study, we hypothesized that
      presence of fQRS on a 12-lead electrocardiogram (ECG) on admission would be
      predictive of adverse outcomes in non-ST elevated myocardial infarction (NSTEMI).
      STUDY DESIGN: A total of 149 NSTEMI patients (112 male, 37 female) were
      retrospectively analyzed. The fQRS pattern was defined as the presence of an
      additional R', notching in the nadir of the S wave, fragmentation of the RS or QS
      complexes in 2 contiguous leads corresponding to a major coronary artery
      territory. The relationship between presence of fQRS on admission on a 12-lead
      ECG, and primary end points [cardiovascular death (CVD)] and secondary end points
      (re-infarction, repeat target vessel revascularization [percutaneous/surgical])
      were assessed. The median follow-up time was 18 (13-24) months. RESULTS: Other
      than age, there were no significant differences in baseline characteristics and
      laboratory findings for patients in the fQRS and non-fQRS groups. The patients in
      the fQRS group were older [64 years vs 59 years, p=0.048]. CVD and re-infarction
      were significantly higher in the fQRS group in the median 18-month follow-up
      (26.1% vs 8.7%, p=0.005; 23.9% vs 10.7%, p=0.035, respectively). By a
      multivariate regression analysis in all 149 patients, age >=65 years and the
      presence of fQRS in a 12-lead ECG on admission were found to be powerful
      independent predictors of cardiovascular mortality (HR: 4.91, 95% CI: 1.60-15.03,
      p=0.005; HR: 2.77, 95% CI: 1.02-7.50, p=0.044, respectively). CONCLUSION:
      Presence of fQRS on a 12-lead ECG on admission is associated with increased long
      term mortality in patients with NSTEMI.

PMID- 25620334
TI  - Rate of blood pressure control and antihypertensive treatment approaches in
      diabetic patients with hypertension.
AB  - OBJECTIVES: Hypertension is a common co-morbidity in patients with type 2
      diabetes. Management of hypertension is of paramount importance in reducing macro
      and microvascular complications of diabetes. The aim of this study is to
      determine the rate of blood pressure control (<140/85 mmHg) in diabetic patients
      with hypertension, and to evaluate the prescribing pattern of antihypertensive
      medications. STUDY DESIGN: This was a prospective, cross-sectional, observational
      study conducted in a tertiary centre in Turkey. Of 707 patients with diabetes,
      500 hypertensive patients were evaluated to determine control of hypertension and
      treatment attitudes. Logistic regression analysis was used to evaluate the
      likelihood of prescription of each class of antihypertensive medications for the
      presence of macro- and microvascular complications. RESULTS: Most of the patients
      (95%) were on antihypertensive therapy. Only 41% achieved target blood pressure
      values (<140/85 mmHg). Renin angiotensin system (RAS) blockers were the most
      frequently (82.4%) prescribed antihypertensive agents, and a combination of RAS
      blockers and diuretics were the most commonly preferred combination therapy. Most
      of the patients were on 1 antihypertensive drug or a combination of 2 drugs
      (39.5% and 44.7%, respectively). Patients with coronary artery disease were more
      likely to receive beta blockers (Odds ratio=3.6, 95% confidence interval=2.3-5.6;
      p<0.001). CONCLUSION: Although most of the diabetic hypertensive patients were on
      hypertensive therapy, more than half had uncontrolled blood pressure.

PMID- 25620335
TI  - [The effects of smokeless tobacco "Maras powder" and smoking on aortic elasticity
      in young adults].
AB  - OBJECTIVES: Stiffness index beta (SIB), aortic strain (AS) and distensibility
      (AD) are the parameters used to assess elasticity of the aorta, and can be
      measured by non-invasive method such as echocardiography. In this study, we aimed
      to analyse the effects of Maras powder and smoking on aortic stiffness by
      comparing young individuals. STUDY DESIGN: The study included 90 male subjects
      aged 18-40 years. 30 subjects were Maras powder users (mean age; 32+/-2), 30 were
      smokers (mean age: 28+/-2) and 30 were healthy volunteers (mean age: 29+/-2).
      After detailed physical examination, all subjects underwent transthoracic
      echocardiography. Systolic and diastolic diameters of the aorta were measured
      from the ascending aorta at modified parasternal long axis views by M-mode
      echocardiography. AS, AD, and SIB were calculated using standard formulae. Group
      parameters were then compared to each other. RESULTS: There was no significant
      difference between the groups in terms of demographic and clinical features,
      including blood pressures, lipid profile and serum creatinine (p>0.05). Although
      AS and AD were lower, and SIB was higher in the Maras powder and smoking groups
      compared to the control group, the difference between groups was not
      statistically significant (for AS: 17.61+/-2.22, 17.75+/-1.93, 18.48+/-2.02
      respectively, for AD: 9.03+/-1.12, 9.14+/-0.96, 9.9+/-1.12, respectively, for
      SIB: 2.72+/-1.07, 2.59+/-0.88, 2.37+/-0.71 respectively, for all p>0.05).
      CONCLUSION: Our study revealed that smoking and Maras powder did not lead to a
      significant change in elasticity of the aorta in individuals under the age of 40.

PMID- 25620336
TI  - [A case of percutaneous mitral balloon valvuloplasty complicated by pericardial
      effusion and thrombus formation on the interatrial septum].
AB  - Percutaneous mitral balloon valvuloplasty (PMBV) is the primary treatment in
      mitral stenosis patients with appropriate valve anatomy with no contraindications
      present. Pericardial effusion, cardiac tamponade and thrombus formation are rare
      but serious complications of this procedure. In the literature, the mortality
      rate associated with PMBV has been reported as 1%. The presence of intracardiac
      thrombus is a contraindication for PMBV. However, thrombus formation during the
      process is a very rare condition. In this case, we present a patient with
      rheumatic mitral stenosis, with both pericardial effusion and intracardiac
      thrombus, after laseration at the base of the left atrium during the
      valvuloplasty procedure. 

PMID- 25620337
TI  - Management of a subclavian artery thrombosis causing acute anterior wall
      infarction and concurrent left arm ischemia in a patient with prior coronary
      bypass.
AB  - We report a 57-year-old patient with acute anterior wall infarction with a
      history of a coronary baypass graft operation in 2007. He also had concurrent
      left arm cyanosis and severe pain. He had received diagnosis of pancreatic
      adenocarcinoma one month previously and had had his first chemotherapy in the
      previous week with gemcitabine and 5-fluorouracil. After the angiography, a giant
      thrombus was detected in the proximal left subclavian artery, deteriorating the
      flows of both left internal mammarian artery (LIMA) to left anterior descending
      (LAD) coronary artery graft, as well as the left brachial artery. The proximal
      subclavian artery was stented and good flow was achieved. Through the LIMA, the
      distal part of LAD, which was totally obstructed with probable distal thrombus
      embolization, was reached and a percutaneous balloon angioplasty performed.
      However, the no-reflow phenomenon was observed in distal LAD. A Fogarty traction
      of thrombus was performed successfully for the revascularization of the left arm.
      Approximately 30 minutes after the procedure, both angina and ST segment
      elevation in ECG were resolved under unfractioned heparin and nitroglycerin
      infusion. However, the patient died due to sepsis seven days after admission to
      hospital. In the literature, there are only a few previous reports on this rare
      clinical entity. The eitology, presentation, and the possible management
      strategies of this clinical entity is presented in this report. 

PMID- 25620338
TI  - [A rare cause of heart failure: aortocaval fistula associated with herniated
      lumbar disc surgery].
AB  - Although aortocaval fistula is mostly encountered as a complication of abdominal
      aortic aneurysms, it may also arise as a complication of lumbar disc surgery.
      Great arteriovenous shunts especially may lead to high-output heart failure in
      due time. In this paper, we aim to present a case of high-output heart failure
      secondary to aortocaval fistule caused by lumbar disc surgery. 

PMID- 25620339
TI  - Retrograde approach for percutaneous closure in a patient with ruptured sinus of
      Valsalva.
AB  - In this report, we present a 37-year-old male with ruptured right sinus of
      Valsalva. He was treated by percutaneous closure of the rupture using the
      retrograde approach. The procedure was performed successfully within 26 minutes.
      We think this approach may be used in future instead of the antegrade approach. 

PMID- 25620340
TI  - Successful treatment of a huge thrombus with thrombolytic therapy in a patient
      with normal left ventricle function and Takayasu arteritis.
AB  - We report a case of thrombus treated with thrombolytic therapy in a patient with
      normal cardiac functions and Takayasu arteritis. A 27-year-old man with a history
      of Takayasu arteritis was admitted to our out-patient clinic with a complaint of
      both right and left foot pain and weakness. In a Doppler ultrasound examination,
      a subtotal thrombotic occlusion was found in the bilateral popliteal arteries. A
      transthoracic echocardiography revealed a left ventricular apical thrombus,
      although both cardiac functions and heart dimensions were normal. Surgical
      excision was recommended to avoid further embolization, but this was refused by
      the patient. We decided to perform thrombolytic treatment. The thrombus in the
      left ventricle was fully resolved by the third day. Perfusion in both feet also
      returned to normal. 

PMID- 25620341
TI  - [Hypertrophic cardiomyopathy and Costello syndrome: review of recent related
      literature with case report].
AB  - Costello syndrome is a rare syndrome characterized by failure to thrive, short
      stature, mental motor retardation, characteristic facial features, macrocephaly,
      a short neck, loose soft skin with deep palmar and plantar creases, and
      hypertrichosis. Cardiac involvement is seen in almost two thirds of patients, and
      is a determinant for the prognosis of Costello syndrome. The most common cardiac
      anomalies are pulmonary stenosis, hypertrophic cardiomyopathy, atrial septal
      defect, ventricular septal defect and arrhytmia. In this report, we present a 14
      month-old female pediatric patient with hypertrophic cardiomyopathy, clinically
      and genetically diagnosed with Costello syndrome. The report also contains a
      review of recent related literature. 

PMID- 25620342
TI  - [Current status of heart transplantation in Turkey].
AB  - Heart failure is a clinical picture that occurs when the heart is unable to
      provide sufficient blood to the tissues and organs due to low performance. In end
      stage heart failure, quality of life and survival rates are affected adversely.
      Heart transplantation is still the best method of treatment in many end-stage
      heart failure patients who remain symptomatic despite guideline-directed medical
      therapy. The current situation of heart transplantation in Turkey is discussed in
      this review. 

PMID- 25620343
TI  - [Performing radial artery puncture].

PMID- 25620344
TI  - Case images: cardiac metastasis of non-Hodgkin's lymphoma presenting with acute
      antero-lateral myocardial infarction with ST-segment elevation.

PMID- 25620345
TI  - Case images: warfarin-induced skin necrosis: a 'novel' solution to an old
      problem.

PMID- 25620346
TI  - Case images: ruptured pseudoaneurysm of mitral-aortic intervalvular fibrosa to
      aorta simulated paravalvular leakage.

PMID- 25620347
TI  - Case images: tricuspid valve prolapse secondary to excessive long chordae
      evaluated by transthoracic echocardiography.

PMID- 25620348
TI  - Case images: double-chambered right ventricle and ventriculo-atrial shunt
      presenting as acute renal failure due to infective endocarditis.

PMID- 25620349
TI  - Trends in health facility deliveries and caesarean sections by wealth quintile in
      Morocco between 1987 and 2012.
AB  - OBJECTIVES: To examine trends in the utilisation of facility-based delivery care
      and caesareans in Morocco between 1987 and 2012, particularly among the poor, and
      to assess whether uptake increased at the time of introduction of policies or
      programmes aimed at improving access to intrapartum care. METHODS: Using data
      from nationally representative household surveys and routine statistics, our
      analysis focused on whether women delivered within a facility, and whether the
      delivery was by caesarean; analyses were stratified by relative wealth quintile
      and public/private sector where possible. A segmented Poisson regression model
      was used to assess whether trends changed at key events. RESULTS: Uptake of
      facility-based deliveries and caesareans in Morocco has risen considerably over
      the past two decades, particularly among the poor. The rate of increase in
      facility deliveries was much faster in the poorest quintile (annual increase RR:
      1.09; 95% CI: 1.07-1.11) than the richest quintile (annual increase RR: 1.01; 95%
      CI: 1.02-1.02). A similar pattern was observed for caesareans (annual increase
      among poorest RR: 1.13; 95% CI: 1.07-1.19 vs. annual increase among richest RR:
      1.08; 95% CI: 1.06-1.10). We found no significant acceleration in trend
      coinciding with any of the events investigated. CONCLUSIONS: Morocco's success in
      improving uptake of facility deliveries and caesareans is likely to be the result
      of the synergistic effects of comprehensive demand and supply-side strategies,
      including a major investment in human resources and free delivery care. Equity
      still needs to be improved; however, the overall trend is positive.

PMID- 25620350
TI  - The -A2518G polymorphism in the MCP-1 gene and inflammatory bowel disease risk: A
      meta-analysis.
AB  - OBJECTIVE: The monocyte chemoattractant protein-1 (MCP-1) -A2518G gene
      polymorphism has been found to be involved in the susceptibility to inflammatory
      bowel disease (IBD); however, the results of existing studies are controversial.
      The aim of this meta-analysis was to assess the relationship between the MCP-1 
      A2518G polymorphism and the risk of IBD. METHODS: PubMed, EMBASE and MEDLINE were
      searched for studies assessing the relationship between the -A2518G polymorphism
      in MCP-1 gene and the risk of IBD. Available data were extracted and
      statistically analyzed using STATA 12.0. RESULTS: A total of five publications
      involving 3137 individuals (1818 IBD cases and 1319 controls) were included in
      the meta-analysis. A combined analysis revealed that the MCP-1 -A2518G
      polymorphism in was a protective factor for GG + AG vs AA (OR 0.76, 95% CI 0.67
      0.87, P = 0.000). Subgroup analysis by ethnicity showed that among European
      patients the AG + GG homozygote, unlike the AA homozygote, had a protective
      effect against IBD (OR 0.73, 95% CI 0.63-0.84, P = 0.000), but did not do so
      among Asian and African patients. Subgroup analysis by disease subtype suggested
      the -A2518G polymorphism in MCP-1 had a protective effect against Crohn's disease
      (OR 0.69, 95% CI 0.58-0.81, P = 0.000), but not against ulcerative colitis.
      CONCLUSIONS: Our meta-analysis suggested that the -A2518G polymorphism in MCP-1
      may be a protective factor for IBD in European populations. Further studies are
      required to confirm these findings.

PMID- 25620352
TI  - The role of the VZn-NO-H complex in the p-type conductivity in ZnO.
AB  - Past research efforts aiming at obtaining stable p-type ZnO have been based on
      complexes involving nitrogen doping. A recent experiment by (J. G. Reynolds et
      al., Appl. Phys. Lett., 2013, 102, 152114) demonstrated a significant (~10(18)
      cm(-3)) p-type behavior in N-doped ZnO films after appropriate annealing. The p
      type conductivity was attributed to a VZn-NO-H shallow acceptor complex, formed
      by a Zn vacancy (VZn), N substituting O (NO), and H interstitial (Hi). We present
      here a first-principles hybrid functional study of this complex compared to the
      one without hydrogen. Our results confirm that the VZn-NO-H complex acts as an
      acceptor in ZnO. We find that H plays an important role, because it lowers the
      formation energy of the complex with respect to VZn-NO, a complex known to
      exhibit (unstable) p-type behavior. However, this additional H atom also occupies
      the hole level at the origin of the shallow behavior of VZn-NO, leaving only two
      states empty higher in the band gap and making the VZn-NO-H complex a deep
      acceptor. Therefore, we conclude that the cause of the observed p-type
      conductivity in experiment is not the presence of the VZn-NO-H complex, but
      probably the formation of the VZn-NO complex during the annealing process. 

PMID- 25620351
TI  - Using topical imiquimod for the management of positive in situ margins after
      melanoma resection.
AB  - The treatment of melanoma in situ (MIS) is controversial with current standard of
      care being surgical excision with clear margins. Alternative topical therapy with
      imiquimod has been proposed in recent studies as a possible treatment for MIS.
      This study aimed to evaluate the use of topical 5% imiquimod as an alternative
      approach for the treatment of residual melanoma in situ after surgical resection
      of the primary lesion. A retrospective chart review of all patients treated with
      topical 5% imiquimod for residual MIS following standard resection with 5-10 mm
      margins at Yale-New Haven Hospital from 2008 through 2013 was performed. The pre-
      and posttreatment results were confirmed by diagnostic tissue biopsy. Twenty-two
      patients were included in the study. One of these 22 patients was lost to follow
      up. Twenty patients (95%) had complete resolution of their residual MIS and 1
      patient did not respond to imiquimod (5%). No reports of recurrences were noted
      at the treatment sites. For patients with residual melanoma in situ after the
      initial excision, topical 5% imiquimod appears to be a reasonable alternative
      treatment with good clinical and histopathologic success rates.

PMID- 25620353
TI  - Import and export of bacterial protein toxins.
AB  - The paper provides a short overview of three investigated bacterial protein
      toxins, colicin M (Cma) of Escherichia coli, pesticin (Pst) of Yersinia pestis
      and hemolysin (ShlAB) of Serratia marcescens. Cma and Pst are exceptional among
      colicins in that they kill bacteria by degrading the murein (peptidoglycan). Both
      are released into the medium and bind to specific receptor proteins in the outer
      membrane of sensitive E. coli cells. Subsequently they are translocated into the
      periplasm by an energy-consuming process using the proton motive force. For
      transmembrane translocation the colicins unfold and refold in the periplasm. In
      the case of Cma the FkpA peptidyl prolyl cis-trans isomerase/chaperone is
      required. ShlA is secreted and activated through ShlB in the outer membrane by a
      type Vb secretion mechanism. 

PMID- 25620355
TI  - [A Research on the origin and development of standardization of Chinese medical
      case records].
AB  - The origin of Chinese medical case history is rather early. Chunyu Yi's medical
      cases (zhen ji) of the Western Han Dynasty were the earliest actual extant
      medical case with the practical contents. In the Ming Dynasty, Han Mao put
      forward firstly the principles of "six aspects must be recorded" for writing the
      pulse record, as the beginning of the standardization of medical case record.
      Later, Wu Kun, Yu Yan, Li Yanzhen, He Lianchen et al. supplemented, adjusted and
      changed the format of medical case record. After 1949, the format of medical case
      record was revised several times to form the national standard. In fact, the
      clinical medical case record is different from the case history. The modern
      medical case record could not reflect fully the thinking process of traditional
      Chinese medicine (TCM) and the essence of the treatment based on syndrome
      differentiation. Exploring the origin and development of the standardization of
      medical case record will benefit for the improvement of modern format of medical
      case record. 

PMID- 25620356
TI  - [Exploring the changes of inheritance model of medical knowledge as viewed from
      the description of physicians in the Song Dynasty].
AB  - From the Southern and Northern Dynasties to the beginning of the Northern Song
      Dynasty, the models of "master and apprentice" and "physician of long family
      tradition for generations" were the main ways for teaching medical knowledge.
      With the rapid amassment of medical books in the Song Dynasty, "reading text"
      became increasingly important and prominent in the inheritance of medical
      knowledge, which could be seen clearly from the descriptions on physicians in the
      Song Dynasty. For instance, Hao Yun's medical knowledge was recorded as a model
      of "master and apprentice" in Hao Yun's Epitaph written by Zhang Xun. However, in
      Ye Mengde's description, this model was played down, while at the same time,
      "reading text" was emphasized. Pang Anshi, though coming from a physician family
      for generations, got rid of some medical knowledge from his own family and turned
      to the medical knowledge by "reading text". According to Pang Anshi's Epitaph
      written by Zhang Lei and Fang ji Zhuan (Biography of Technicians) in Song shi
      (The Song History), Pang Anshi was a typical model of becoming a famous physician
      by "reading text". In the Epitaph, Pang Anshi's brilliance was stressed, and in
      the latter, "reading text" was more important and the family tradition was
      denied. In the description of the Song Dynasty, Chen Zhaoyu's wonderful medical
      skills was coming from the "practice", and "reading text" was denied right away.
      What is more, "reading text" was introspected and criticized through Chen
      Zhaoyu's lip. The different descriptions of the Song Dynasty reflected the change
      of inheritance model of medical knowledge. 

PMID- 25620354
TI  - Capsular polysaccharides from Cryptococcus neoformans modulate production of
      neutrophil extracellular traps (NETs) by human neutrophils.
AB  - In the present study, we characterized the in vitro modulation of NETs
      (neutrophil extracellular traps) induced in human neutrophils by the
      opportunistic fungus Cryptococcus neoformans, evaluating the participation of
      capsular polysaccharides glucuronoxylomanan (GXM) and glucuronoxylomannogalactan
      (GXMGal) in this phenomenon. The mutant acapsular strain CAP67 and the capsular
      polysaccharide GXMGal induced NET production. In contrast, the wild-type strain
      and the major polysaccharide GXM did not induce NET release. In addition, C.
      neoformans and the capsular polysaccharide GXM inhibited PMA-induced NET release.
      Additionally, we observed that the NET-enriched supernatants induced through
      CAP67 yeasts showed fungicidal activity on the capsular strain, and neutrophil
      elastase, myeloperoxidase, collagenase and histones were the key components for
      the induction of NET fungicidal activity. The signaling pathways associated with
      NET induction through the CAP67 strain were dependent on reactive oxygen species
      (ROS) and peptidylarginine deiminase-4 (PAD-4). Neither polysaccharide induced
      ROS production however both molecules blocked the production of ROS through PMA
      activated neutrophils. Taken together, the results demonstrate that C. neoformans
      and the capsular component GXM inhibit the production of NETs in human
      neutrophils. This mechanism indicates a potentially new and important modulation
      factor for this fungal pathogen. 

PMID- 25620357
TI  - [Deciphering the argots of the names of materia medica and its dosage in the Yi
      lin kou pu liu zhi mi shu (A Secret Medical Book of Six Therapies in Rhymes of
      Medical Professionals)].
AB  - Yi lin kou pu liu zhi mi shu (A Secret Medical Book of Six Therapies in Rhymes of
      Medical Professionals) was additionally compiled, supplemented and annotated by
      Zhou Sheng, a famous doctor of the Qing Dynasty, based on Yi lin kou pu (Rhymes
      of Medical Professionals) which was composed by Lu Qi. The book contains four
      volumes in total, dealing mainly with the miscellaneous diseases of internal
      medicine, as well as external medicine, gynecology, and pediatrics etc. The
      syndrome differentiation and treatment, prescriptions and medications in this
      book has its own characteristic with rather high academic value and practical
      significance. There were 20 drug names were deciphered by the argots, for
      instance, "you che" was the argot of golden thread, and "wu yue (May)" was the
      argot of medicinal evodia fruit, etc. In addition, the argots were often used to
      decipher numerals and quantifiers, for example, "su, qi, zi, qi, man" referring
      to 1, 2, 3, 4, 5 respectively, and "huo, pu, xiang, feng, lai" referring to 6, 7,
      8, 9, 10 respectively, and "qing",""zhong","xi" referring to qian, liang and fen
      respectively. Hence, deciphering of these argots could help to understand and
      apply these prescriptions correctly. 

PMID- 25620358
TI  - [Exploration and analysis of the thought of medical education in the Shanghai New
      Chinese Medical College].
AB  - Shanghai New Chinese Medical College set up by Zhu Nanshan and his sons, Zhu
      Xiaonan and Zhu Hegao, was a medical college of traditional Chinese medicine
      (TCM) with the most innovative spirit in modern time. Its affiliated research
      institute held the principle of "realizing the scientific truth of TCM, training
      TCM advanced talents", marking the beginning of the pioneering of "scientific
      TCM". The educational plan, clinical research and academic organization based on
      "carrying forward the quintessence of Chinese culture, absorbing and digesting
      the new knowledge" showed a certain influence at home and abroad. The College
      advocated the combination of communicating with famous physicians and the study
      of theory, cultivation of students' organization and academic society, launching
      of journals, and organizing students' research associations was aiming at the
      satisfaction of the social needs and teaching orientation. Its running experience
      provided useful reference for modern TCM medical education. 

PMID- 25620359
TI  - [Changes and establishment of the principle of "Unity of traditional Chinese
      medicine and western medicine"].
AB  - "Unity of traditional Chinese and western medicine" was one of the three major
      health work principles at the early founding of the People's Republic of China.
      It was not only a choice of political strategy in line with the lack of
      contemporary health-care resources, but also a part of the revolutionary heritage
      for more than 20 years in the process of the Chinese Communist Party from the
      preliminary "application of both traditional and western medicine" to the making
      of the principles of both "cooperation of traditional Chinese and western
      medicine" and "unity of traditional Chinese and western medicine". All this was
      closely related to the concrete environment of the Chinese health work of various
      stages of Yan'an period with strong revolutionary atmosphere and was not the
      professional demand of the health workers, rather, this principle set up in 1950
      was the result of the careful consideration of Mao Zedong and an adjustment
      guided under the revolutionary framework of Neo-democracy set up under the
      guidance of the Common Principle which was a bettered adaptation to the
      contemporary national condition. 

PMID- 25620360
TI  - [Academic heritage of Jiu huang ben cao (Materia Medica for Relief of Famines) in
      Japan].
AB  - Jiu huang ben cao (Materia Medica for Relief of Famines) was the first monograph
      on famines herbal in the history of China, which creates a new research field of
      edible plants. Around the middle and late 17th century, Jiu huang ben cao was
      spread to Japan and aroused great attention of famous Japanese herbalists. Thus,
      all versions of different edition systems were circulated in Japan. Later, some
      famous Japanese scholar ssuccessively quoted texts of Jiu huang ben cao from the
      Nong zheng quan shu (Whole book on Agricultural Administration) spread in Japan,
      and block-printed it as an independent work. As a result, Jiu huang ben cao
      virtually circulated widely in Japan. 

PMID- 25620361
TI  - [An introduction on the editions of Zhang Gao's Yi shuo (Medical Narrations)].
AB  - Zhang Gao's Yi shuo (Medical Narrations) of the Southern Song Dynasty had 2 kinds
      of editions: domestic editions and foreign editions. The former includes 1 Song
      edition, 14 Ming editions, 3 Qing editions and 25 editions after the Republic of
      China. The latter, mainly 2 classes, the Japanese edition and Korean printing
      type edition. In the Ming Dynasty, the editions of Yi shuo generated 2 branches:
      inherited edition and supplementary edition. The inherited editions include Gu
      Dingfang's edition, Zhang Yaode's edition, Wu Mianxue's edition, Wu Zhongheng's
      edition, Wang Kentang's edition, editions from Si ku quan shu (Imperial
      Collection of Four), stereotype edition of the 3th year of Xuantong reign (1911)
      from Shanghai Civilization Bookstore, edition of the 2(nd) year of Manji of Japan
      etc. The supplemental editions include Zhang Zili's edition, Shen Fan's edition,
      Fu Feng'ao's edition, transcript of the late Ming Dynasty preserved in the
      Library of Peking University, and Korean printing type edition etc. 

PMID- 25620362
TI  - [A Brief Description on the origin and evolution of the Section on Eyes in Zheng
      zhi zhun sheng (Standards for Syndrome Identification and Treatment)].
AB  - Compiled by Wang Kentang, Zheng zhi zhun sheng (Standards for Syndrome
      Identification and Treatment) has 11 versions falling into 4 classes: (1) The
      first xylographic version of Wanli reign system, including the first carved
      version of Renyin year or 30(th) year of Wanli (1602) of the Ming Dynasty, the
      Japanese Kanbun Dynasty 1670 version of Tongtuo Book Store version, the version
      of Yimao year or 14(th) year of Kangxi reign (1675) of the Qing Dynasty from the
      Jintan Yu's Sanctum, the revised version of Jimao year or 38(th) year of Kangxi
      reign (1699) of the Qing Dynasty from the Jintan Yu's Sanctum, and the version of
      the 25(th) year of Guangxu reign (1899) of the Qing Dynasty from the Shancheng
      Sanctum of Western Shu (Sichuan), altogether 4 versions; (2) The system of
      Xiujing Sanctum, including the version of Guichou year or the 58(th) year of
      Qianlong reign (1793) of the Qing Dynasty from the Kim's version of Xiujing
      Sanctum, the version of Renchen year or the 18(th) year of Guangxu reign (1892)
      of the Qing Dynasty from the revised version of Shijing Sanctum of Guangzhou, the
      xylographic version of Jiuxueshan Sanctum of the Qing Dynasty, altogether 3
      versions; (3) The system of Compendium of Illustrated Books, referring to the
      printing version of the Renchen year or 18(th) year of Guangxu reign (1892) from
      the Printing House of Shanghai Compendium of Illustrated Book; (4) The
      xylographic version of Daiyue Building system, referring to the version of Jisi
      year or 14th year of Qianlong reign (1749) of the Qing Dynasty from the Daiyue
      Building; (5) The system of Jiusitang Sanctum xylographic version of the Qing
      Dynasty from Jiaxing, referring to the said version; (6) The system of
      lithographic versions: Hongbaozhai of Shanghai in 1912 and Saoyeshan Sanctum of
      Shanghai in 1935. 

PMID- 25620363
TI  - Solution Phase Exciton Diffusion Dynamics of a Charge-Transfer Copolymer PTB7 and
      a Homopolymer P3HT.
AB  - Using ultrafast polarization-controlled transient absorption (TA) measurements,
      dynamics of the initial exciton states were investigated on the time scale of
      tens of femtoseconds to about 80 ps in two different types of conjugated polymers
      extensively used in active layers of organic photovoltaic devices. These polymers
      are poly(3-fluorothienothiophenebenzodithiophene) (PTB7) and poly-3
      hexylthiophene (P3HT), which are charge-transfer polymers and homopolymers,
      respectively. In PTB7, the initial excitons with excess vibrational energy
      display two observable ultrafast time constants, corresponding to coherent
      exciton diffusion before the vibrational relaxation, and followed by incoherent
      exciton diffusion processes to a neighboring local state after the vibrational
      relaxation. In contrast, P3HT shows only one exciton diffusion or conformational
      motion time constant of 34 ps, even though its exciton decay kinetics are
      multiexponential. Based on the experimental results, an exciton dynamics
      mechanism is conceived taking into account the excitation energy and structural
      dependence in coherent and incoherent exciton diffusion processes, as well as
      other possible deactivation processes including the formation of the pseudo
      charge-transfer and charge separate states, as well as interchain exciton hopping
      or coherent diffusion. 

PMID- 25620364
TI  - Treatment of ferrous-NTA-based NO x scrubber solution by an up-flow anaerobic
      packed bed bioreactor.
AB  - A bench scale system consisting of an up-flow packed bed bioreactor (UAPBR) made
      of polyurethane foam was used for the treatment and regeneration of aqueous
      solution of ferrous-NTA scrubbed with nitric oxide (NO). The biomass in the UAPBR
      was sequentially acclimatized under denitrifying and iron reducing conditions
      using ethanol as electron donor, after which nitric oxide (NO) gas was loaded
      continuously to the system by absorption. The system was investigated for
      different parameters viz. pH, removal efficiency of nitric oxide, biological
      reduction efficiency of Fe(II)NTA-NO and COD utilization. The Fe(II)NTA-NO
      reduction efficiency reached 87.8 % at a loading rate of 0.24 mmol L(-1) h(-1),
      while the scrubber efficiency reached more than 75 % with 250 ppm NO. Stover
      Kincannon and a Plug-flow kinetic model based on Michaelis-Menten equation were
      used to describe the UAPBR performance with respect to Fe(II)NTA-NO and COD
      removal. The Stover-Kincannon model was found capable of describing the Fe(II)NTA
      NO reduction (R m = 8.92 mM h(-1) and K NO = 11.46 mM h(-1)) while plug-flow
      model provided better fit to the COD utilization (U m = 66.62 mg L(-1) h(-1), K
      COD = 7.28 mg L(-1)). Analyses for pH, Fe(III)NTA, ammonium, nitrite
      concentration, and FTIR analysis of the medium samples indicated degradation of
      NTA, which leads to ammonium and nitrite accumulation in the medium, and affect
      the regeneration process.

PMID- 25620365
TI  - Metabolic flux analysis of Escherichia coli MG1655 under octanoic acid (C8)
      stress.
AB  - Systems metabolic engineering has made the renewable production of industrial
      chemicals a feasible alternative to modern operations. One major example of a
      renewable process is the production of carboxylic acids, such as octanoic acid
      (C8), from Escherichia coli, engineered to express thioesterase enzymes. C8,
      however, is toxic to E. coli above a certain concentration, which limits the
      final titer. (13)C metabolic flux analysis of E. coli was performed for both C8
      stress and control conditions using NMR2Flux with isotopomer balancing. A mixture
      of labeled and unlabeled glucose was used as the sole carbon source for bacterial
      growth for (13)C flux analysis. By comparing the metabolic flux maps of the
      control condition and C8 stress condition, pathways that were altered under the
      stress condition were identified. C8 stress was found to reduce carbon flux in
      several pathways: the tricarboxylic acid (TCA) cycle, the CO2 production, and the
      pyruvate dehydrogenase pathway. Meanwhile, a few pathways became more active: the
      pyruvate oxidative pathway, and the extracellular acetate production. These
      results were statistically significant for three biological replicates between
      the control condition and C8 stress. As a working hypothesis, the following
      causes are proposed to be the main causes for growth inhibition and flux
      alteration for a cell under stress: membrane disruption, low activity of electron
      transport chain, and the activation of the pyruvate dehydrogenase regulator
      (PdhR). 

PMID- 25620366
TI  - Enhanced production of polysialic acid by metabolic engineering of Escherichia
      coli.
AB  - A number of reports have described the production of polysialic acid (PSA),
      focusing on the fermentation and purification of PSA. However, little work has
      been done to strengthen the synthetic pathway of PSA to improve PSA production.
      In this study, an efficient process for enhanced production of PSA using a
      recombinant Escherichia coli strain was developed. To improve the PSA production
      efficiency, the key enzymes of PSA synthetic pathway were overexpressed
      separately or in combination, including N-acetylneuraminate (Neu5Ac) 7-O(or 9-O)
      acetyltransferase (NeuD), CMP-Neu5Ac synthetase (NeuA), and alpha-Neu5Ac alpha
      2,8-sialyltransferase (NeuS). The PSA production was significantly improved by
      coexpression of NeuD and NeuA. In terms of the efficiency, NeuD was considered as
      the most important factor. Secondly, the competing pathway of intermediate Neu5Ac
      was blocked by nanA deletion. The efficient PSA-producing strain E. coli
      SA9DeltananA/pDB1S-DA was constructed, and 16.15 +/- 1.45 g/L PSA was obtained in
      the fed-batch culture. The production of PSA by engineered strain was increased
      by 85 % compared to the original strain. These results provide evidence for
      improvement of PSA production by regulation of the PSA biosynthetic pathway. The
      high productivity of our process should make it a promising cost-effective
      resource for PSA.

PMID- 25620367
TI  - In vitro and in vivo characterization of a new recombinant antimicrobial peptide,
      MP1102, against methicillin-resistant Staphylococcus aureus.
AB  - Currently, more antimicrobial drug candidates are urgently needed to combat the
      rise in drug-resistance among pathogenic microbes. A new antimicrobial peptide,
      MP1102, a variant of NZ2114, was designed, evaluated, and overexpressed in Pichia
      pastoris. The total secreted protein in cultures reached 695 mg/l, and the
      concentration of the recombinant MP1102 (rMP1102) was 292 mg/l. rMP1102 was
      purified from the fermentation supernatant by one-step cation exchange
      chromatography to obtain a yield of 197.1 mg/l with 96.4 % purity. rMP1102
      exhibited potent activity against Gram-positive bacteria, and its minimum
      inhibitory concentrations (MICs) for four Staphyloccocus aureus (S. aureus)
      strains ranged from 0.028 to 0.11 MUM, and it had stronger activity (MIC = 0.04
      to 0.23 MUM) to 20 clinical isolates of MRSA (cMRSA) than rNZ2114 (MIC = 0.11 to
      0.90 MUM). rMP1102 was shown to kill over 99.9 % of tested S. aureus cells within
      6 h when treated at one, two, and four times its MIC and over 90 % of S. aureus
      cells within 12 h at concentrations of 5, 10, and 20 mg/kg in a mouse thigh
      infection model. The higher sensitivity of MRSA to MP1102 than to its parental
      peptide, NZ2114, indicated by this initial pharmacodynamic analysis suggests a
      possible difference in the killing mechanism of these two molecules. rMP1102
      caused less than 0.05 % hemolytic activity at 128 MUg/ml and exhibited good
      thermostability from 20 to 80  degrees C, with its highest activity being
      observed at pH 8.0. These results suggest that this yeast expression system is
      feasible for large-scale production, and rMP1102 exerted stronger activity
      against S. aureus than NZ2114 via a different mechanism and exhibited potential
      as a new antimicrobial agent for S. aureus, especially MRSA infections. 

PMID- 25620368
TI  - Production and applications of rosmarinic acid and structurally related
      compounds.
AB  - Rosmarinic acid (alpha-o-caffeoyl-3,4-dihydroxyphenyllactic acid; RA) is a
      naturally occurring hydroxylated compound commonly found in species of the
      subfamily Nepetoideae of the Lamiaceae and Boraginaceae, such as Rosmarinus
      officinalis, Salvia officinalis, and Perilla frutescens. RA is biosynthesized
      from the amino acids L-phenylalanine and L-tyrosine by eight enzymes that include
      phenylalanine ammonia lyase and cinnamic acid 4-hydroxylase. RA can also be
      chemically produced by the esterification of caffeic acid and 3,4
      dihydroxyphenyllactic acid. RA and its numerous derivatives containing one or two
      RA with other aromatic moieties are well known and include lithospermic acid,
      yunnaneic acid, salvianolic acid, and melitric acid. Recently, RA and its
      derivatives have attracted interest for their biological activities, which
      include anti-inflammatory, anti-oxidant, anti-angiogenic, anti-tumor, and anti
      microbial functions. Clinically, RA attenuates T cell receptor-mediated
      signaling, attenuates allergic diseases like allergic rhinitis and asthma, and
      2,4-dinitrofluorobenzene-induced atopic dermatitis-like symptoms, protects from
      neurotoxicity, and slows the development of Alzheimer's disease. These attributes
      have increased the demand for the biotechnological production and application of
      RA and its derivatives. The present review discusses the function and application
      of RA and its derivatives including the molecular mechanisms underlying clinical
      efficacy. 

PMID- 25620369
TI  - Characterization and gene cloning of a maltotriose-forming exo-amylase from
      Kitasatospora sp. MK-1785.
AB  - A maltotriose-forming amylase (G3Amy) from Kitasatospora sp. MK-1785 was
      successfully isolated from a soil sample by inhibiting typical extracellular
      alpha-amylases using a proteinaceous alpha-amylase inhibitor. G3Amy was purified
      from the MK-1785 culture supernatant and characterized. G3Amy produced
      maltotriose as the principal product from starch and was categorized as an exo
      alpha-amylase. G3Amy could also transfer maltotriose to phenolic and alcoholic
      compounds. Therefore, G3Amy can be useful for not only maltotriose manufacture
      but also maltooligosaccharide-glycoside synthesis. Further, the G3Amy gene was
      cloned and expressed in Escherichia coli cells. Analysis of its deduced amino
      acid sequence revealed that G3Amy consisted of an N-terminal GH13 catalytic
      domain and two C-terminal repeat starch-binding domains belonging to CBM20. It is
      suggested that natural G3Amy was subjected to proteolysis at N-terminal region of
      the anterior CBM20 in the C-terminal region. As with natural G3Amy, recombinant
      G3Amy could produce and transfer maltotriose from starch. 

PMID- 25620370
TI  - Impacts of CO2 concentration on growth, lipid accumulation, and carbon
      concentrating-mechanism-related gene expression in oleaginous Chlorella.
AB  - Biodiesel production by microalgae with photosynthetic CO2 biofixation is thought
      to be a feasible way in the field of bioenergy and carbon emission reduction.
      Knowledge of the carbon-concentrating mechanism plays an important role in
      improving microalgae carbon fixation efficiency. However, little information is
      available regarding the dramatic changes of cells suffered upon different
      environmental factors, such as CO2 concentration. The aim of this study was to
      investigate the growth, lipid accumulation, carbon fixation rate, and carbon
      metabolism gene expression under different CO2 concentrations in oleaginous
      Chlorella. It was found that Chlorella pyrenoidosa grew well under CO2
      concentrations ranging from 1 to 20 %. The highest biomass and lipid productivity
      were 4.3 g/L and 107 mg/L/day under 5 % CO2 condition. Switch from high (5 %) to
      low (0.03 %, air) CO2 concentration showed significant inhibitory effect on
      growth and CO2 fixation rate. The amount of the saturated fatty acids was
      increased obviously along with the transition. Low CO2 concentration (0.03 %) was
      suitable for the accumulation of saturated fatty acids. Reducing the CO2
      concentration could significantly decrease the polyunsaturated degree in fatty
      acids. Moreover, the carbon-concentrating mechanism-related gene expression
      revealed that most of them, especially CAH2, LCIB, and HLA3, had remarkable
      change after 1, 4, and 24 h of the transition, which suggests that Chlorella has
      similar carbon-concentrating mechanism with Chlamydomonas reinhardtii. The
      findings of the present study revealed that C. pyrenoidosa is an ideal candidate
      for mitigating CO2 and biodiesel production and is appropriate as a model for
      mechanism research of carbon sequestration. 

PMID- 25620371
TI  - Low-temperature biodegradation of aniline by freely suspended and magnetic
      modified Pseudomonas migulae AN-1.
AB  - Aniline is of great environmental concern with regards to widespread occurrence
      in water and soil and increasing threat into the life forms. Bioremediation
      involving the use of degrading bacterium in the removal of aniline is the most
      promising process, yet inhibited under low temperature usually. In the present
      study, a new psychrotrophic bacterial strain isolated from groundwater,
      designated AN-1, was shown to be capable of aniline degradation in a
      concentration range of 135-2202 mg L(-1) within 72 h at 10  degrees C. Strain AN
      1 was proposed to be a Pseudomonas migulae group of bacteria based on the
      evolutionary relationship and the morphological and biochemical characteristics.
      The pH, NaH2PO4, and aniline concentration were used as independent variables to
      optimize the aniline removal by AN-1 at 10  degrees C, and a statistically
      significant (R (2) = 0.9230, p < 0.005) quadratic polynomial mathematical model
      was suggested. Moreover, an efficient biocomposite by assembling Fe3O4
      nanoparticles onto the surface of AN-1 cells was constructed. Compared with free
      cells, the microbial cell/Fe3O4 biocomposite had the same biodegradation activity
      but exhibited remarkable reusability. This study highlights AN-1 might be a
      promising candidate for aniline removal from wastewater at low temperatures.

PMID- 25620372
TI  - Levels of maternal care.
AB  - In the 1970s, studies demonstrated that timely access to risk-appropriate
      neonatal and obstetric care could reduce perinatal mortality. Since the
      publication of the Toward Improving the Outcome of Pregnancy report, more than 3
      decades ago, the conceptual framework of regionalization of care of the woman and
      the newborn has been gradually separated with recent focus almost entirely on the
      newborn. In this current document, maternal care refers to all aspects of
      antepartum, intrapartum, and postpartum care of the pregnant woman. The proposed
      classification system for levels of maternal care pertains to birth centers,
      basic care (level I), specialty care (level II), subspecialty care (level III),
      and regional perinatal health care centers (level IV). The goal of regionalized
      maternal care is for pregnant women at high risk to receive care in facilities
      that are prepared to provide the required level of specialized care, thereby
      reducing maternal morbidity and mortality in the United States. 

PMID- 25620373
TI  - Evidence for passive chemical camouflage in the parasitic mite Varroa destructor.
AB  - Social insect colonies provide a stable and safe environment for their members.
      Despite colonies being heavily guarded, parasites have evolved numerous
      strategies to invade and inhabit these hostile places. Two such strategies are
      (true) chemical mimicry via biosynthesis of host odor, and chemical camouflage,
      in which compounds are acquired from the host. The ectoparasitic mite Varroa
      destructor feeds on hemolymph of its honey bee host, Apis mellifera. The mite's
      odor closely resembles that of its host, which allows V. destructor to remain
      undetected as it lives on the adult host during its phoretic phase and while
      reproducing on the honeybee brood. During the mite life cycle, it switches
      between host adults and brood, which requires it to adjust its profile to mimic
      the very different odors of honey bee brood and adults. In a series of transfer
      experiments, using bee adults and pupae, we tested whether V. destructor changes
      its profile by synthesizing compounds or by using chemical camouflage. We show
      that V. destructor required direct access to host cuticle to mimic its odor, and
      that it was unable to synthesize host-specific compounds itself. The mite was
      able to mimic host odor, even when dead, indicating a passive physico-chemical
      mechanism of the parasite cuticle. The chemical profile of V. destructor was
      adjusted within 3 to 9 h after switching hosts, demonstrating that passive
      camouflage is a highly efficient, fast and flexible way for the mite to adapt to
      a new host profile when moving between different host life stages or colonies. 

PMID- 25620374
TI  - Antioxidant Activities of Caralluma tuberculata on Streptozotocin-Induced
      Diabetic Rats.
AB  - Preclinical Research The aim of this study was to elucidate the antioxidant
      effects of Caralluma tuberculata (C. tuberculata) in streptozotocin (STZ)-induced
      diabetic rats. Diabetes was induced in male Wistar rats with an intraperitoneal
      injection of STZ at dose of 60 mg/kg body weight. Three days after diabetes
      induction, powdered aerial part of plant at doses of 100 and 200 mg/kg body
      weight were gavaged orally for a period of 45 days. The diabetes significantly
      decreased the activities of superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase, and level of total thiol in liver, kidney, and
      heart of animals (P < 0.05). In contrast, a significant increase in the levels of
      protein carbonyl was observed in diabetic rats compared with control animals (P <
      0.05). Oral treatment of diabetic rats with C. tuberculata showed ameliorative
      effects on blood glucose and markers of oxidative stress in a dose-dependent
      manner. Altered levels of all oxidative stress parameters in tissues of diabetic
      rats reverted back to those normal animals after the treatment with dose of 200 
      mg/kg /day of plant materials. It seems that the appropriate dose of C.
      tuberculata has both antihyperglycemic and antioxidant activities in STZ-induced
      diabetic rats. Therefore, it can have preventive properties on oxidative stress
      induced diabetic complications. Drug Dev Res 76 : 40-47, 2015.

PMID- 25620375
TI  - Occurrence of OXA-48 and NDM-1 carbapenemase-producing Klebsiella pneumoniae in a
      Moroccan university hospital in Casablanca, Morocco.
AB  - The purpose of this investigation was to determine the prevalence and the
      characteristics of carbapenemase-producing Klebsiellapneumoniae isolates
      recovered from various clinical specimens in the university hospital of
      Casablanca, in Morocco. We conducted a prospective study on a total of 166 K.
      pneumoniae isolates collected from June to August 2011. The strains suspected to
      carry carbapenemase showed reduced susceptibility to imipenem or ertapenem. The
      PCR and a sequencing strategy were used to identify carbapenemases, expended
      spectrum beta-lactamases (ESBL), plasmid-mediated AmpC beta-lactamases, plasmid
      mediated quinolone resistance and aminoglycoside resistance determinants. The
      clonal relationships between isolates were analyzed by pulsed field gel
      electrophoresis (PFGE). Among the 166 K. pneumoniae isolates studied, 11 (6%)
      were carbapenemases producers, 9 of which harbored blaOXA-48 and 2 were positive
      for blaNDM-1. All carbapenemase-producing K. pneumoniae were also ESBL producers
      and the blaCTX-M-15 was the most frequent ESBL gene detected (n=9), blaCTX-M-28
      and blaSHV-28 were also encountered in one isolate each. The K.pneumoniae
      isolates carried also non-ESBL genes blaTEM-1 (n=9), blaSHV-1 (n=8) and blaOXA-1
      (n=3). Five isolates harbored qnr genes, qnrS1 (n=3) and qnrB1 (n=2) variants.
      Six isolates were positive for aac(6')-Ib-cr gene and two for aac(3)-II gene. The
      class 1 integron was detected in five isolates. PFGE has revealed the presence of
      a clonal dissemination in our hospital. The results of conjugation experiments
      indicated that blaOXA-48+blaCTX-M-15, blaOXA-48+blaCTX-M-28, blaNDM-1+blaCTX-M
      15+blaTEM-1+blaOXA-1+qnrS1+aac(6')-Ib-cr and blaNDM-1+blaCTX-M-15+blaTEM
      1+qnrB1+aac(6')-Ib-cr genes were co-transferred and that these genes were carried
      by a conjugative plasmid of high molecular weight. 

PMID- 25620376
TI  - Molecular detection and genetic diversity of Babesia gibsoni in dogs in
      Bangladesh.
AB  - Babesia gibsoni is a tick-borne hemoprotozoan parasite of dogs that often causes
      fever and hemolytic illness. Detection of B. gibsoni has been predominantly
      reported in Asian countries, including Japan, Korea, Taiwan, Malaysia, Bangladesh
      and India. The present study shows the first molecular characterization of B.
      gibsoni detected from dogs in Bangladesh. Blood samples were collected on FTA(r)
      Elute cards from 50 stray dogs in Mymensingh District in Bangladesh. DNA eluted
      from the cards was subjected to nested PCR for the 18S rRNA gene of Babesia
      species. Approximately 800bp PCR products were detected in 15 of 50 dogs (30%).
      Based on restriction fragment length polymorphism (RFLP) and direct sequencing of
      the PCR products, all parasite isolates were identified as B. gibsoni.
      Furthermore, the BgTRAP (B. gibsoni thrombospondin-related adhesive protein) gene
      fragments were detected in 13 of 15 18S rRNA gene PCR positive blood samples.
      Phylogenetic analysis of the BgTRAP gene revealed that B. gibsoni parasites in
      Bangladesh formed a cluster, which was genetically different from other Asian B.
      gibsoni isolates. In addition, tandem repeat analysis of the BgTRAP gene clearly
      showed considerable genetic variation among Bangladeshi isolates. These results
      suggested that B. gibsoni parasites in a different genetic clade are endemic in
      dogs in Bangladesh. Further studies are required to elucidate the origin,
      distribution, vector and pathogenesis of B. gibsoni parasites circulating in dogs
      in Bangladesh. 

PMID- 25620377
TI  - Home is where hearth is.

PMID- 25620378
TI  - Pioglitazone adjunctive therapy for depressive episode of bipolar disorder: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The antidepressive effect of pioglitazone has been noted in patients
      with major depressive disorder in absence of metabolic syndrome. This study was
      conducted to evaluate the safety and efficacy of pioglitazone in patients with
      bipolar depression without concomitant metabolic syndrome or diabetes. METHOD:
      Forty-eight outpatients with the diagnosis of bipolar I disorder and a major
      depressive episode participated in a parallel, randomized, double-blind, placebo
      controlled trial, and 44 patients underwent 6-week treatment with either
      pioglitazone (30 mg/day) or placebo as an adjunctive treatment to lithium.
      Therapeutic serum lithium levels of 0.6-0.8 mEq/L were required for two or more
      consecutive weeks immediately before starting pioglitazone and during the 6-week
      study. Patients were evaluated using Hamilton Depression Rating Scale (HDRS) and
      Young Mania Rating Scale (YMRS) at baseline and weeks 1, 2, 4, and 6. The primary
      outcome was to evaluate the efficacy of pioglitazone in improving the depressive
      symptoms. RESULT: General linear model repeated measures showed significant
      effect for time * treatment interaction on the HDRS scores [F(2.78, 116.65) =
      4.77, P = .005]. Significantly greater reduction was observed in HDRS scores in
      the pioglitazone group than the placebo group from baseline HDRS score at weeks
      2, 4, and 6, P = .003, .006, and .006, respectively. No serious adverse event was
      observed. CONCLUSION: This study showed that pioglitazone could be a tolerable
      and effective adjunctive therapy for improving depressive symptoms in bipolar
      disorder without type 2 diabetes or metabolic syndrome.

PMID- 25620379
TI  - The drs tumor suppressor regulates glucose metabolism via lactate dehydrogenase
      B.
AB  - Previously, we showed that drs contributes to suppression of malignant tumor
      formation in drs-knockout (KO) mice. In this study, we demonstrate the regulation
      of glucose metabolism by drs using comparisons of drs-KO and wild-type (WT) mouse
      embryonic fibroblasts (MEFs). Extracellular acidification, lactate concentration,
      and glucose consumption in drs-KO cells were significantly greater than those in
      WT cells. Metabolomic analyses also confirmed enhanced glycolysis in drs-KO
      cells. Among glycolysis-regulating proteins, expression of lactate dehydrogenase
      (LDH)-B was upregulated at the post-transcriptional level in drs-KO cells and
      increased LDH-B expression, LDH activity, and acidification of culture medium in
      drs-KO cells were suppressed by retroviral rescue of drs, indicating that LDH-B
      plays a critical role for glycolysis regulation mediated by drs. In WT cells
      transformed by activated K-ras, expression of endogenous drs mRNA was markedly
      suppressed and LDH-B expression was increased. In human cancer cell lines with
      low drs expression, LDH-B expression was increased. Database analyses also showed
      the correlation between downregulation of drs and upregulation of LDH-B in human
      colorectal cancer and lung adenocarcinoma tissues. Furthermore, an LDH inhibitor
      suppressed anchorage-independent growth of human cancer cells and MEF cells
      transformed by activated K-ras. These results indicate that drs regulates glucose
      metabolism via LDH-B. Downregulating drs may contribute to the Warburg effect,
      which is closely associated with malignant progression of cancer cells.

PMID- 25620380
TI  - Comparison of aroma-active compounds and sensory characteristics of durian (Durio
      zibethinus L.) wines using strains of Saccharomyces cerevisiae with odor activity
      values and partial least-squares regression.
AB  - The study evaluated the effects of five different strains (GRE, RC212, Lalvin
      D254, CGMCC2.4, and CGMCC2.23) of the yeast Saccharomyces cerevisiae on the
      aromatic characteristics of fermented durian musts. In this work, 38 and 43
      compounds in durian juices and wines were analyzed by gas chromatography-mass
      spectrometry (GC-MS) and GC-pulsed flame photometric detection (GC-PFPD) with the
      aid of stir bar sorptive extraction (SBSE), respectively. According to the
      measured odor activity values (OAV), only 11 and 15 aroma compounds had OAVs >1
      in durian juices or wines, among which 2,3-butanedione, 3-methylbutanol, dimethyl
      sulfide, dimethyl disulfide, methyl ethyl disulfide, ethyl 2-methylbutanoate,
      ethyl butanoate, and ethyl octanoate were major contributors to the aroma of
      juices and wines. Partial least-squares regression (PLSR) was used to detect
      positive correlations between sensory analysis and aroma compounds. The results
      showed that the attributes were closely related to aroma compounds. 

PMID- 25620381
TI  - Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL
      report.
AB  - Rhinitis is an umbrella term that encompasses many different subtypes, several of
      which still elude complete characterization. The concept of phenotyping, being
      the definition of disease subtypes on the basis of clinical presentation, has
      been well established in the last decade. Classification of rhinitis entities on
      the basis of phenotypes has facilitated their characterization and has helped
      practicing clinicians to efficiently approach rhinitis patients. Recently, the
      concept of endotypes, that is, the definition of disease subtypes on the basis of
      underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic,
      overlapping, and may evolve into one another, thus rendering clear-cut
      definitions difficult. Nevertheless, a phenotype-/endotype-based classification
      approach could lead toward the application of stratified and personalized
      medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes
      and endotypes are described, and rhinitis diagnosis and management approaches
      focusing on those phenotypes/endotypes are presented and discussed. We emphasize
      the concept of control-based management, which transcends all rhinitis subtypes. 

PMID- 25620382
TI  - Update on fungal respiratory disease in horses.
AB  - Fungal respiratory disease is a rare occurrence in horses. Fungal organisms are
      ubiquitous in the equine environment; however, there is a geographic
      predisposition for disease development, with fungal respiratory infections seen
      more commonly by practitioners working in tropical or subtropical environments.
      Diagnosis and treatment of fungal respiratory infections pose a challenge for the
      equine practitioner, and the prognosis for complete resolution of infection is
      often guarded; however, new antifungal medications are likely to improve
      treatment success. This article summarizes the available literature regarding the
      cause, diagnosis, and treatment of equine fungal respiratory disease. 

PMID- 25620383
TI  - The ethanol extract of Eucommia ulmoides Oliv. leaves inhibits disaccharidase and
      glucose transport in Caco-2 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The cortex and leaves of Eucommia ulmoides Oliv.
      from the family Eucommiaceae are traditional Chinese medicines (TCM). Roasted
      Eucommiae cortex is utilized to reinforce the muscles and lungs, lower blood
      pressure and improve the tone of the liver and kidneys, while Eucommia ulmoides
      leaves (EUL) are traditionally used as folk remedies to treat diabetes. MATERIALS
      AND METHODS: EUL extract, obtained by ethanol (40%) was loaded onto an AB-8
      macroporous resin column, and washed thoroughly with 0, 20, 40, 60, and 80% (v/v)
      ethanol for purification. The ethanol eluents of EUL were first determined to
      inhibit alpha-glucosidase in vitro, and then the inhibition of the most potent
      eluent, i.e., 20% ethanol eluent of EUL (EEUL), against carbohydrate-degrading
      enzymes and glucose transport in Caco-2 cells was demonstrated. And computational
      modeling was also employed to evaluate the binding modes of compounds identified
      in EEUL by GC-MS analysis. RESULTS: EEUL significantly inhibited alpha
      glucosidase (43.08+/-0.55%) competitively in vitro and concentration-dependently
      suppressed sucrase (IC50, 0.07mg/mL) and maltase (IC50, 0.53mg/mL) in Caco-2
      cells. The inhibitory activity of EEUL (0.02mg/mL) on sucrase and maltase was
      identical to that of acarbose (0.02mg/mL). Moreover, 1.0mg/mL EEUL decreased
      glucose transport in cells by 26.25+/-0.86%. GC-MS revealed that EEUL was rich in
      monosaccharides, polyphenols and esters, which comprised 47.16% of the total
      extract. Computational modeling showed that catechin, alpha-d-glucopyranose and d
      mannono-1,4-lactone docked tightly into the sucrase active site with low binding
      energies. CONCLUSION: These results indicated that EEUL exerted marked anti
      hyperglycemic effects by suppressing disaccharidases and glucose transporters.
      Therefore, EUL is a beneficial source of inhibitors of carbohydrate-utilizing
      enzymes, glucose transporters, and potentially hyperglycemia.

PMID- 25620384
TI  - Evaluation of hypoglycemic effects of polyphenols and extracts from Penthorum
      chinense.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh has a long history of
      use as a health food and folk medicine to alleviate "heat"-associated disorders,
      promote circulation and diuresis, and to treat liver problems, and to protect the
      spleen. In this study we provide experimental evidence for the clinical use of
      Penthorum chinense in the treatment of diabetes mellitus. The aim of the study
      was to investigate the hypoglycemic effects of extracts and active constituents
      from Penthorum chinense. MATERIALS AND METHODS: High fat diet and STZ (35mg/kg)
      induced diabetic rats were administered with Penthorum chinense extract at graded
      oral doses (150 and 300mg/kg/day, ig.) for 2 weeks. A range of parameters,
      including blood glucose and lipid, serum insulin, glucose tolerance, were tested
      to evaluate its anti-hyperglycemic effects. Moreover, oral starch tolerance test
      (OSTT) was performed to test the level of postprandial glucose after
      administrating Penthorum chinense extract. In vitro study, the Penthorum chinense
      extracts and purified Penthorum chinense polyphenols were tested for alpha
      amylase inhibitory activity. The polyphenols were determined by UPLC-Q-TOF mass
      spectrometry and NMR. RESULTS: The Penthorum chinense extract possessed anti
      hyperglycemic activities as shown by the decreased serum levels of glycosylated
      hemoglobulin A1C (HbA1c), triglyceride(TG), total cholesterol (TC), and low
      density lipoprotein-cholesterol (LDL-C), as well as increased serum levels of
      high density lipoprotein-cholesterol (HDL-C) and insulin. Penthorum chinense
      extract also improved the oral glucose tolerance test (OGTT) to a certain degree.
      Moreover, the OSTT study showed that in diabetic rats, the extract (600mg/kg)
      caused a significant hypoglycemic effect with a blood glucose reduction of 42% at
      60min. To identify the active constituents, three polyphenols, pinocembrin-7-O
      [4",6"-hexahydroxydiphenoyl]-beta-d-glucose (1), pinocembrin-7-O-[3"-O-galloyl
      4", 6"-hexahydroxydiphenoyl]-beta- d-glucose (2), and thonningianin A (3) were
      isolated from Penthorum chinense. Compounds 1-3 moderately inhibited alpha
      amylase activity, with IC50 values of 0.14, 0.03, and 0.08umol/ml, respectively.
      CONCLUSIONS: The folk medicinal plant, Penthorum chinense produced a moderated
      anti-hyperglycemic effect on STZ-induced diabetic rats and starch induced
      postprandial hyperglycemic mice.

PMID- 25620385
TI  - Conservation of fungal and animal nicotinamide adenine dinucleotide phosphate
      oxidase complexes.
AB  - Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are a group of
      eukaryotic flavoenzymes that catalyse the reduction of dioxygen to the superoxide
      anion using electrons provided by NADPH. An integral membrane flavocytochrome
      b558 heterodimer, composed of the catalytic subunit gp91(phox) and the adaptor
      protein p22(phox), is essential for catalytic activity of the mammalian Nox2
      complex. Two homologues of the mammalian gp91(phox), NoxA and NoxB, have been
      identified in fungi and shown to be crucial for distinct fungal cell
      differentiation and developmental processes, but to date, no homologue of the
      p22(phox) adaptor protein has been identified. Isolation of a mutant from
      Podospora anserina with a phenotype identical to a previously characterised
      PaNox1 mutant, combined with phylogenetic analysis, identified a fungal homologue
      of p22(phox) called PaNoxD. The same adaptor protein was shown to be a component
      of the Botrytis cinerea NoxA complex as supported by the identical phenotypes of
      the bcnoxA and bcnoxD mutants and direct physical interaction between BcNoxA and
      BcNoxD. These results suggest that NoxA/NoxD is the fungal equivalent of the
      mammalian gp91(phox)/p22(phox) flavocytochrome complex. Tetraspanin (Pls1)
      mutants of P. anserina and B. cinerea have identical phenotypes to noxB mutants,
      suggesting that Pls1 is the corresponding integral membrane adaptor for assembly
      of the NoxB complex.

PMID- 25620386
TI  - Amphotericin B deoxycholate nasal spray administered to hematopoietic stem cell
      recipients with prior fungal colonization of the upper airway passages is
      associated with low rates of invasive fungal infection.
AB  - BACKGROUND: Invasive fungal infections cause major problems during hematopoietic
      stem cell transplantation (HSCT). Fungal colonization of the upper airway
      passages occurs frequently, and may serve as a portal of entry for potentially
      life-threatening fungal infections, especially in immunocompromised patients.
      METHODS: A clinical practice was instituted at Northwestern Memorial Hospital in
      Chicago in 2005, to administer amphotericin B deoxycholate nasal spray (ABNS)
      0.5% to all HSCT recipients with fungal colonization of their nasal passages, in
      addition to standard oral antifungal prophylaxis. RESULTS: Among 1945 HSCT
      patients treated during the study period, 109 patients were identified with
      positive fungal surveillance cultures. CONCLUSION: Breakthrough fungal infections
      occurred in only 2 patients (2%), thus in this select group of HSCT recipients,
      ABNS administration is associated with a very low rate of breakthrough infection.

PMID- 25620387
TI  - Practice variation in Aspergillus prophylaxis and treatment among lung transplant
      centers: a national survey.
AB  - BACKGROUND: Fungal infections remain a substantial cause of mortality in lung
      transplant (LTx) recipients, yet no comprehensive consensus guidelines have been
      established for antifungal prophylaxis and treatment of Aspergillus infection in
      these patients. METHODS: A cross-sectional study surveyed the directors from 27
      of 64 (45.5%) active LTx centers in the United States to examine clinical
      practice variations in Aspergillus prophylaxis and treatment of colonization and
      invasive aspergillosis (IA) in LTx recipients. RESULTS: Antifungal prophylaxis
      increased from 52.3% in 2011 to 77.8% in 2013, with the most common agent being
      inhaled amphotericin B (61.9%), followed by oral voriconazole (51.9%). A total of
      74.1% of centers treat Aspergillus airway colonization, with 80.0% of centers
      using oral voriconazole. All centers treat IA, with 92.6% using oral
      voriconazole. The duration of Aspergillus prophylaxis and treatment of
      colonization or IA varied widely across centers from 3 months to >1 year. A total
      of 51.9% of centers reported internal practice variations in the treatment of IA.
      Factors guiding treatment decisions included microbiologic culture and
      sensitivity (74.1%), ease of administration (59.3%), interaction with other
      medications (55.5%), side effect profile (51.8%), and center guidelines (48.1%).
      Although 85.2% of LTx centers recommended routine skin cancer screening for LTx
      recipients, only 44.4% of LTx centers reported having a dedicated transplant
      dermatologist. CONCLUSION: Most active US LTx centers currently employ antifungal
      prophylaxis and treat Aspergillus colonization and IA, although choice of agent,
      route of administration, and duration of therapy across and within centers
      continue to differ substantially. The number of transplant dermatologists
      available among US LTx centers is limited. Overall, a strong need exists for more
      comprehensive consensus guidelines to direct antifungal prophylaxis and treatment
      of Aspergillus infection in LTx recipients.

PMID- 25620388
TI  - Cryptosporidium infection after renal transplantation in an endemic area.
AB  - BACKGROUND: Cryptosporidium is one of the common causes of infective diarrhea in
      post-transplant patients in endemic areas. However, data are limited on
      Cryptosporidium infection in recipients of solid organ transplantation. The aim
      of this study was to determine the incidence, disease manifestation, management,
      and outcome of Cryptosporidium infection in living-donor renal transplant
      recipients (RTR). METHODS: We performed a detailed retrospective review of the
      data on all RTR who had diarrheal illness requiring evaluation and
      hospitalization, and Cryptosporidium infection. RESULTS: During the study period,
      119/1235 (8.98%) RTR developed diarrhea, and Cryptosporidium was found in 34/119
      (28.5%). Nine of 680 (1.3%) patients were on a cyclosporine (CSA)-based regimen,
      and 25/643 (3.8%) patients were on a tacrolimus (Tac)-based regimen. The relative
      risk of developing Cryptosporidium infection was lower on the CSA-based regimen,
      compared with the Tac-based regimen (odds ratio [OR]: 0.35, 95% confidence
      interval [CI]: 0.17-0.72, P = 0.003). Twelve of the 34 patients had acute graft
      dysfunction, mainly caused by combined Tac toxicity and dehydration. Mean serum
      creatinine and trough Tac level were 2.04 +/- 0.65 mg/dL and 8.24 +/- 1.19 ng/dL,
      respectively. Nitazoxanide alone was used in 13 patients, and nitazoxanide in
      combination with fluoroquinolone in 21 patients, with duration of treatment
      ranging from 16 to 60 days. Tac was changed to CSA in 8/11 patients. The
      clearance of cysts and response to nitazoxanide alone were significantly lower,
      compared with combination therapy (61.53% vs. 95.23%, P = 0.01, 38.46 vs. 85.71%,
      P = 0.004, respectively). The OR for cyst clearance and response was also
      significantly lower with nitazoxanide alone, in comparison with combination
      therapy (OR: 0.65, 95% CI: 0.34-0.92, P = 0.01, OR: 0.45, 95% CI: 0.21-0.81,
      respectively). Four (16%) of 24 patients with response had relapse. CONCLUSION:
      Patients with Tac and mycophenolate mofetil combination therapy had a
      significantly high risk of Cryptosporidium infection. Cryptosporidial infection
      may require prolonged nitazoxanide therapy, either alone or in combination, with
      or without reduction in immunosuppression.

PMID- 25620389
TI  - Tuberculosis before hematopoietic stem cell transplantation in patients with
      hematologic diseases: report of a single-center experience.
AB  - BACKGROUND: Few reports discuss the optimal management of patients diagnosed with
      tuberculosis (TB) before scheduled stem cell transplantation (SCT), who then
      proceed with transplantation. METHODS: We found 13 patients with TB before SCT
      (proven, n = 9; probable, n = 3; possible, n = 1) in the medical records of our
      institution. RESULTS: Most of the patients had pulmonary TB (n = 8; disseminated,
      n = 2; extrapulmonary, n = 3). Eight of 9 patients with proven disease had SCT
      after at least 100 days of anti-tuberculous medication, ranging from 103 to 450
      days. None of those patients suffered TB-related events after SCT. However, 1
      patient with proven pulmonary TB who underwent SCT after only 40 days of anti
      tuberculous therapy subsequently died of TB meningitis. Patients with possible
      and probable disease had their transplants after 6-176 days of anti-tuberculous
      medication, and all were alive at the time of analysis. The entire duration of
      anti-tuberculous medication was 12 months in most cases. With a follow-up
      duration ranging from 0.7 to 87.5 months, 4 patients died, but TB was the cause
      of death in only 1 case. CONCLUSION: In conclusion, for proven cases of TB, SCT
      after >100 days of anti-tuberculous medication is probably feasible and safe, in
      terms of TB control, in patients with various hematologic diseases.

PMID- 25620390
TI  - Safety and tolerability of clofazimine as salvage therapy for atypical
      mycobacterial infection in solid organ transplant recipients.
AB  - BACKGROUND: The treatment of Mycobacterium avium complex (MAC) requires
      prolonged, multidrug therapy, which is often not well tolerated. In solid organ
      transplant (SOT) recipients, drug-drug interactions complicate treatment further.
      Failure or intolerance requires the use of salvage regimens, and clofazimine is
      one of the drugs that can be used. No data are available on the safety and
      tolerability of clofazimine for the treatment of MAC in SOT recipients. METHODS:
      Retrospective review of all SOT recipients treated for MAC infection with
      clofazimine at a large transplant center between 2006 and 2013. RESULTS: Five SOT
      recipients received clofazimine as salvage therapy. Transplanted organs were
      lungs in 3 patients, and kidney and liver in 1 patient each. Infection was
      diagnosed at a median of 22 months (range 4-57) post transplant. Sites of
      infection were the lungs in 2 patients, and septic arthritis, mesenteric, and
      disseminated disease in 1 patient each. All patients received standard anti-MAC
      therapy for a median of 26 weeks (range 18-45) before starting clofazimine.
      Indications for use of clofazimine included a lack of response to previous
      therapy (3 patients), and poor tolerance of other regimens (3 patients). All
      patients received at least 2 additional drugs besides clofazimine. Median
      duration of clofazimine-containing regimen was 8 months (range 2-18). Clofazimine
      was discontinued because of gastrointestinal intolerance in 1 of the 5 patients.
      The most common adverse event from clofazimine was skin discoloration, in 60% of
      patients. No hepatotoxicity or hematologic toxicity occurred. Microbiological
      clearance and resolution of clinical disease was documented in 2 of 5 patients;
      and 2 of the 5 patients died of other causes while on therapy. CONCLUSIONS:
      Clofazimine appears safe and may be considered as a salvage therapeutic option in
      SOT recipients with MAC infection who are intolerant or unresponsive to standard
      therapy. The small sample size does not allow conclusions regarding efficacy.

PMID- 25620391
TI  - Presentation and management of mycotic pseudoaneurysm after kidney
      transplantation.
AB  - Pseudoaneurysms (PAs) developing at the site of vascular anastomosis after organ
      transplantation are a rare but serious complication. We report a series of 3
      cases of PA observed in a single center over a period of 18 years. The mode of
      presentation was acute bleeding in 2 cases. In the third patient, who underwent
      combined kidney and pancreas transplantation, the PA on the renal graft was
      discovered by chance. Graft removal associated with iliac artery ligation and
      extra-anatomic femoro-femoral bypass represents the standard treatment. However,
      interposition of a venous homograft may allow preservation of inferior limb
      perfusion and possibly graft salvage.

PMID- 25620393
TI  - Retraction statement: 'Glabridin attenuates the migratory and invasive capacity
      of breast cancer cells by activating microRNA-200c' by Xianqing Ye, Fei Jiang,
      Yuan Li, Juan Mu, Lu Si, Xingxing Wang, Shilong Ning and Zhong L.

PMID- 25620392
TI  - Antiretroviral blood levels in HIV/HCV-coinfected patients with cirrhosis after
      liver transplant: a report of three cases.
AB  - Since the introduction of combined antiretroviral therapy, human immunodeficiency
      virus (HIV) infection is no longer a contraindication for solid organ
      transplantation. In HIV/hepatitis C virus (HCV)-coinfected patients undergoing
      liver transplantation, HCV-related cirrhosis, drug-drug interactions, and
      calcineurin inhibitors-related toxicity affect clinical outcomes. Therapeutic
      drug monitoring can be useful to assess antiretroviral over- or underexposure in
      this cohort. We report the clinical characteristics along with antiretroviral
      trough levels of maraviroc, darunavir, and etravirine in 3 HIV/HCV-coinfected
      liver transplant recipients who developed post-transplant liver cirrhosis. 

PMID- 25620395
TI  - What is the minimum number of patients for quality control of lung cancer
      management in Norway?
AB  - INTRODUCTION: There are few data available on the optimal number of lung cancer
      patients needed to generate and compare estimates of quality between units
      managing lung cancer. The number of lung cancer patients per management unit
      varies considerably in Norway, where there are 42 hospitals that treated between
      1 and 454 lung cancer patients in 2011. AIMS: To estimate the differences in
      quality indicators that are of sufficient importance to change a pulmonary
      physician's lung cancer management program, and to estimate the size of the
      patient samples necessary to detect such differences. METHOD: Twenty-six
      physicians were asked about the relative differences from a national average of
      quality indicators that would change their own lung cancer management program.
      Sample sizes were calculated to give valid estimates of quality of a management
      unit based on prevalence of quality indicators and minimally important
      differences (MID). RESULTS: The average MID in quality indicators that would
      cause a change in management varied from 18% to 24% among 26 chest physicians,
      depending on the indicator. CONCLUSIONS: To generate precise estimates for
      quality control of lung cancer care in Norway, the number of management units
      must be reduced. Given the present willingness of chest physicians to change
      their procedures for management of lung cancer according to the results of
      quality control indicators, we recommend a maximum of 10 units with a minimum of
      200 incident lung cancer patients per year for each management center.

PMID- 25620396
TI  - In vitro selection of DNAs with an increased propensity to form small circles.
AB  - A protocol was devised to select for DNA molecules that efficiently form circles
      from a library of 126 base pair DNAs containing 90 randomized base pairs. After
      six rounds of selection, individual molecules from the library showed 20- to 100
      fold greater j-factors compared with the starting library, validating the
      selection protocol. High-throughput sequencing revealed a sinusoidal pattern of
      enrichment and de-enrichment of A/T dinucleotides in the random region with a
      10.4 base pair period associated with the helicity of DNA. A similar, but more
      moderate pattern of C/G dinucleotides was offset by precisely half a helical
      turn. While C/G dinucleotide enrichments were evenly distributed, A/T
      dinucleotide enrichments displayed a preference to cluster in individual DNA
      molecules. The most highly enriched 10 base pair sequences in the random region
      contained adjacent blocks of A/T and C/G trinucleotides present in some, but not
      all, rapidly cyclizing molecules. The phased dinucleotide enrichments closely
      match those present in accurately mapped yeast nucleosomes, confirming the
      importance of DNA bending in nucleosome formation. However, at certain sites the
      nucleosomal DNAs show dinucleotide enrichments that differ substantially from the
      cyclization data. These discrepancies can often be correlated with sequence
      specific contacts that form between histones and DNA.

PMID- 25620397
TI  - Epicardial fat and liver disease; the contribution of cardio autonomic nervous
      system function.

PMID- 25620398
TI  - A nuclear magnetic resonance method for probing molecular influences of substrate
      loading in nonribosomal peptide synthetase carrier proteins.
AB  - Carrier proteins (CPs) play a central role in nonribosomal peptide synthetases
      (NRPSs) as they shuttle covalently attached substrates between active sites.
      Understanding how the covalent attachment of a substrate (loading) influences the
      molecular properties of CPs is key to determining the mechanism of NRPS
      synthesis. However, structural studies have been impaired by substrate
      hydrolysis. Here, we used nuclear magnetic resonance spectroscopy to monitor
      substrate loading of a CP and to overcome hydrolysis. Our results reveal the
      spectroscopic signature of substrate loading and provide evidence of molecular
      communication between an NRPS carrier protein and its covalently attached
      substrate. 

PMID- 25620399
TI  - Effect of thermal state and thermal comfort on cycling performance in the heat.
AB  - PURPOSE: To determine the effect of thermal state and thermal comfort on cycling
      performance in the heat. METHODS: Seven well-trained male triathletes completed 3
      performance trials consisting of 60 min cycling at a fixed rating of perceived
      exertion (14) followed immediately by a 20-km time trial in hot (30 degrees C)
      and humid (80% relative humidity) conditions. In a randomized order, cyclists
      either drank ambient-temperature (30 degrees C) fluid ad libitum during exercise
      (CON), drank ice slurry (-1 degrees C) ad libitum during exercise (ICE), or
      precooled with iced towels and ice slurry ingestion (15 g/kg) before drinking ice
      slurry ad libitum during exercise (PC+ICE). Power output, rectal temperature, and
      ratings of thermal comfort were measured. RESULTS: Overall mean power output was
      possibly higher in ICE (+1.4%+/-1.8% [90% confidence limit]; 0.4> smallest
      worthwhile change [SWC]) and likely higher PC+ICE (+2.5%+/-1.9%; 1.5>SWC) than in
      CON; however, no substantial differences were shown between PC+ICE and ICE
      (unclear). Time-trial performance was likely enhanced in ICE compared with CON
      (+2.4%+/-2.7%; 1.4>SWC) and PC+ICE (+2.9%+/-3.2%; 1.9>SWC). Differences in mean
      rectal temperature during exercise were unclear between trials. Ratings of
      thermal comfort were likely and very likely lower during exercise in ICE and
      PC+ICE, respectively, than in CON. CONCLUSIONS: While PC+ICE had a stronger
      effect on mean power output compared with CON than ICE did, the ICE strategy
      enhanced late-stage time-trial performance the most. Findings suggest that
      thermal comfort may be as important as thermal state for maximizing performance
      in the heat.

PMID- 25620400
TI  - Rest boosts the long-term retention of spatial associative and temporal order
      information.
AB  - People retain more new verbal episodic information for at least 7 days if they
      rest for a few minutes after learning than if they attend to new information. It
      is hypothesized that rest allows for superior consolidation of new memories. In
      rodents, rest periods promote hippocampal replay of a recently travelled route,
      and this replay is thought to be critical for memory consolidation and subsequent
      spatial navigation. If rest boosts human memory by promoting hippocampal
      replay/consolidation, then the beneficial effect of rest should extend to complex
      (hippocampal) memory tasks, for example, tasks probing associations and
      sequences. We investigated this question via a virtual reality route memory task.
      Healthy young participants learned two routes to a 100% criterion. One route was
      followed by a 10-min rest and the other by a 10-min spot the difference game. For
      each learned route, participants performed four delayed spatial memory tests
      probing: (i) associative (landmark-direction) memory, (ii) cognitive map
      formation, (iii) temporal (landmark) order memory, and (iv) route memory. Tests
      were repeated after 7 days to determine any long-term effects. No effect of rest
      was detected in the route memory or cognitive map tests, most likely due to
      ceiling and floor effects, respectively. Rest did, however, boost retention in
      the associative memory and temporal order memory tests, and this boost remained
      for at least 7 days. We therefore demonstrate that the benefit of rest extends to
      (spatial) associative and temporal order memory in humans. We hypothesise that
      rest allows superior consolidation/hippocampal replay of novel information
      pertaining to a recently learned route, thus boosting new memories over the long
      term.

PMID- 25620401
TI  - The explicit mentioning of reporting guidelines in urogynecology journals in
      2013: A bibliometric study.
AB  - AIMS: Poor reporting of research may limit critical appraisal and
      reproducibility, whereas adherence to reporting guidelines (RG) can guarantee
      completeness and transparency. We aimed to determine the explicit citing of RGs
      (CONSORT, PRISMA, STROBE) in urogynecology articles in 2013, the requirements of
      relevant journals and a potential difference between urogynecology and general
      gynecology journals. METHODS: All urogynecologic articles published between
      January and December 2013 in the journals NAU, IUJ, FPMRS, GREEN, AJOG, and BJOG
      were included. Issues were searched for systematic reviews, RCTs, cohort studies,
      case-control studies and cross-sectional studies. Each electronic article was
      searched for the term PRISMA, CONSORT, or STROBE according to the study design.
      Instructions to Authors of the six journals were screened for requirement of
      using RGs. RESULTS: We included 296 articles (243 observational studies, 40 RCTs,
      and 13 systematic reviews). The use of PRISMA guidelines was explicitly declared
      in 54% of systematic reviews, CONSORT guidelines were referenced in 25% of RCTs
      and STROBE in 1.2% of observational studies. The use of CONSORT is required by
      all journals except FPMRS. PRISMA and STROBE are only compulsory in the journals
      GREEN, AJOG, and BJOG. The overall rate of explicit mentioning of RGs comparing
      urogynecology and general gynecology journals was 6.7% versus 7.1%, respectively.
      CONCLUSIONS: The explicit mentioning of RGs was on a relatively low level. A
      slightly higher adherence was recognized among general gynecology journals
      compared to urogynecology journals. Stronger efforts should be taken to further
      promote the use of RGs in urogynecology.

PMID- 25620402
TI  - Impact of gestational diabetes mellitus in the maternal-to-fetal transport of
      nutrients.
AB  - Gestational diabetes mellitus (GDM) is a metabolic disorder prevalent among
      pregnant women. This disease increases the risk of adverse perinatal outcomes and
      diseases in the offspring later in life. The human placenta, the main interface
      between the maternal and fetal blood circulations, is responsible for the
      maternal-to-fetal transfer of nutrients essential for fetal growth and
      development. In this context, the aim of this article is to review the latest
      advances in the placental transport of macro and micronutrients and how they are
      affected by GDM and its associated conditions, such as elevated levels of
      glucose, insulin, leptin, inflammation, and oxidative stress. Data analyzed in
      this article suggest that GDM and its associated conditions, particularly high
      levels of glucose, leptin, and oxidative stress, disturb placental nutrient
      transport and, consequently, fetal nutrient supply. As a consequence, this
      disturbance may contribute to the fetal and postnatal adverse health outcomes
      associated with GDM. 

PMID- 25620403
TI  - Using oral agents to manage gestational diabetes: what have we learned?
AB  - Insulin has been the mainstay of treatment of diabetes during pregnancy for
      decades. Although glyburide and metformin are classified as category B during
      pregnancy, recent research has suggested that these oral agents alone or in
      conjunction with insulin may be safe for the treatment of gestational diabetes
      (GDM). This paper summarizes the data on the use of glyburide and metformin for
      treatment of GDM. 

PMID- 25620404
TI  - Type 2 diabetes in youth in South Asia.
AB  - People of South Asian origin are at a high risk of developing diabetes compared
      to that of other ethnic groups. Recent evidence suggests an emerging epidemic of
      youth-onset type 2 diabetes (T2DM) in the region, in parallel with the childhood
      obesity epidemic. Many risk factors such as foetal and early-life influences, the
      South Asian phenotype, family history of diabetes and environment factors are
      responsible for the early occurrence of T2DM in South Asia. The high risk
      supports the need for the opportunistic screening of children and adolescents for
      diabetes in South Asian countries. Early detection, lifestyle modification,
      weight reduction and drugs are central to the care of children with T2DM. Both
      population-based preventive strategies and interventions targeting children and
      adolescents with obesity and impaired glucose tolerance are required to combat
      the epidemic of youth-onset T2DM in South Asia. 

PMID- 25620407
TI  - Salmonella modulation of the phagosome membrane, role of SseJ.
AB  - Salmonellae have the ability to invade, persist and replicate within an
      intracellular phagosome termed the Salmonella-containing vacuole (SCV).
      Salmonellae alter lipid and protein content of the SCV membrane and manipulate
      cytoskeletal elements in contact with the SCV using the Salmonella pathogenicity
      island 1 (SPI-2) type III secretion system effectors. These modifications result
      in microtubular-based movement and morphological changes, which include endosomal
      tubulation of the SCV membrane. SseJ is a SPI-2 effector that localizes to the
      cytoplasmic face of the SCV and esterifies cholesterol through its
      glycerophospholipid : cholesterol acyltransferase activity. SseJ enzymatic
      activity as well as localization to the SCV are determined by binding to the
      small mammalian GTPase, RhoA. This review will focus on current knowledge about
      the role of SseJ in SCV membrane modification and will discuss how the hypothesis
      that a major role of SPI-2 effectors is to modify SCV protein and lipid content
      to promote bacterial intracellular survival.

PMID- 25620406
TI  - Material need support interventions for diabetes prevention and control: a
      systematic review.
AB  - Unmet material needs, such as food insecurity and housing instability, are
      associated with increased risk of diabetes and worse outcomes among diabetes
      patients. Healthcare delivery organizations are increasingly held accountable for
      health outcomes that may be related to these "social determinants," which are
      outside the scope of traditional medical intervention. This review summarizes the
      current literature regarding interventions that provide material support for
      income, food, housing, and other basic needs. In addition, we propose a
      conceptual model of the relationship between unmet needs and diabetes outcomes
      and provide recommendations for future interventional research. 

PMID- 25620405
TI  - From pathobiology to the targeting of pericytes for the treatment of diabetic
      retinopathy.
AB  - Pericytes, the mural cells that constitute the capillaries along with endothelial
      cells, have been associated with the pathobiology of diabetic retinopathy;
      however, therapeutic implications of this association remain largely unexplored.
      Pericytes appear to be highly susceptible to the metabolic challenges associated
      with a diabetic environment, and there is substantial evidence that their loss
      may contribute to microvascular instability leading to the formation of
      microaneurysms, microhemorrhages, acellular capillaries, and capillary
      nonperfusion. Since pericytes are strategically located at the interface between
      the vascular and neural components of the retina, they offer extraordinary
      opportunities for therapeutic interventions in diabetic retinopathy. Moreover,
      the availability of novel imaging methodologies now allows for the in vivo
      visualization of pericytes, enabling a new generation of clinical trials that use
      pericyte tracking as clinical endpoints. The recognition of multiple signaling
      mechanisms involved in pericyte development and survival should allow for a
      renewed interest in pericytes as a therapeutic target for diabetic retinopathy. 

PMID- 25620408
TI  - A Russian adaptation of the tinnitus handicap inventory.
AB  - OBJECTIVE: To establish a Russian version of the English THI. DESIGN: The English
      THI (THI-E) was translated into Russian by two bilingual investigators,
      independently. The final Russian THI version (THI-R) was constructed by a third
      investigator, from the two translations. This version was administered to fifty
      consecutive patients at a tinnitus clinic. Participants also assessed the
      loudness of their tinnitus, and completed the Russian versions of the Beck's
      depression inventory and the state anxiety Inventory. STUDY SAMPLE: The
      participants were fifty consecutive patients (older than 18 years of age with a
      tinnitus lasting over three months) who were treated at a tinnitus clinic.
      RESULTS: A very good internal consistency was found (alpha = 0.94), with
      significant correlation between the THI-R score and the Beck depression inventory
      score. Factor analysis confirmed a uni-dimensional structure of the inventory.
      CONCLUSIONS: A valid and reliable THI-R questionnaire was constructed.

PMID- 25620409
TI  - Changes in chemical coding of sympathetic chain ganglia (SChG) neurons supplying
      porcine urinary bladder after botulinum toxin (BTX) treatment.
AB  - Botulinum toxin (BTX) is a neurotoxin used in medicine as an effective drug in
      experimental therapy of neurogenic urinary bladder disorders. We have
      investigated the influence of BTX on the chemical coding of sympathetic chain
      ganglia (SChG) neurons supplying the porcine urinary bladder. The toxin was
      injected into the wall of the bladder. SChG neurons were visualized by a
      retrograde tracing method with fluorescent tracer fast blue (FB) and their
      chemical coding was investigated by double-labelling immunohistochemistry with
      antibodies against dopamine beta-hydroxylase (DbetaH; a marker of noradrenergic
      neurons), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP),
      somatostatin (SOM), galanin (GAL), Leu(5)-enkephalin (L-ENK) and neuronal nitric
      oxide synthase (nNOS). In both the control (n = 5) and BTX-treated pigs (n = 5),
      the vast majority (91 +/- 2.3 % and 89.8 +/- 2.5 %, respectively) of FB-positive
      (FB+) nerve cells were DbetaH+. BTX injections caused a decrease in the number of
      FB+/DbetaH+ neurons that were immunopositive to NPY (39.5 +/- 4.5 % vs 74.5 +/-
      11.9 %), VIP (8.9 +/- 5.3 % vs 22.3 +/- 8.8 %), SOM (5.8 +/- 2.3 % vs 17.4 +/-
      3.7 %) or GAL (0.9 +/- 1.2 % vs 5.4 +/- 4.4 %) and a distinct increase in the
      number of FB+/DbetaH+ neurons that were immunoreactive to L-ENK (3.7 +/- 2.9 % vs
      1.1 % +/- 0.8 %) or nNOS (7.7 +/- 3.5 % vs 0.8 +/- 0.6 %). Our study provides
      novel evidence that the therapeutic effects of BTX on the mammalian urinary
      bladder are partly mediated by SChG neurons.

PMID- 25620411
TI  - Quantitative in situ proteomics; a proposed pathway for quantification of
      immunohistochemistry at the light-microscopic level.
AB  - Companion diagnostics, tests that purport to classify patients into "responders"
      and "non-responders" for a specified targeted therapy, demand methods that
      quantify the actual amount of the corresponding target molecule in tumors from
      these patients. Various methods are employed depending upon the nature of the
      target. Many of the candidate therapeutic agents target the abnormal expression
      of a protein, the detection of which lends itself to an immunohistochemistry
      (IHC) approach. This review focuses on IHC with formalin-fixed paraffin-embedded
      (FFPE) tissues for purely pragmatic reasons; first, the morphologic information
      pertaining to the tumor is of value and should not be discarded as in extraction
      type assays; second, FFPE tissues are mostly what we have to hand at the time
      that the diagnostic question is posed. During the four decades of employment of
      IHC involving the production of a variety of special stains used in the diagnosis
      or classification of tumors, we have acquired some bad habits, essentially when
      judging the IHC result via the perception of a "good" stain that "pleases the
      eye" of the user pathologist, and nothing more. This review takes, as its basic
      premise, the notion that IHC can be upgraded from its use as a qualitative
      special staining method to an accurate and reliable quantitative "tissue-based
      immunologic assay". If accomplished, this enhanced IHC assay would serve
      accurately to quantify proteins in tissue sections, analogous to the use of the
      ELISA (enzyme-linked immunosorbent assay) method in the clinical laboratory. The
      necessary steps for converting IHC to a tissue-based ELISA-like immunoassay of
      immediate practical use are reviewed with constructive suggestions for steps that
      can be (must be) taken to achieve the practical reality of quantitative in situ
      proteomics. 

PMID- 25620412
TI  - Keratins and skin disease.
AB  - Mutations in keratin genes cause a diverse spectrum of skin, hair and mucosal
      disorders. Cutaneous disorders include epidermolysis bullosa simplex,
      palmoplantar keratoderma, epidermolytic ichthyosis and pachyonychia congenita.
      Both clinical and laboratory observations confirm a major role for keratins in
      maintaining epidermal cell-cell adhesion. When normal tissue homeostasis is
      disturbed, for example, during wound healing and cancer, keratins play an
      important non-mechanical role. Post-translational modifications including
      glycosylation and phosphorylation of keratins play an important role in
      protection of epithelial cells from injury. Keratins also play a role in
      modulation of the immune response. A current focus in the area of keratins and
      disease is the development of new treatments including small inhibitory RNA
      (siRNA) to mutant keratins and small molecules to modulate keratin expression. 

PMID- 25620413
TI  - Highly regioselective osmium-catalyzed hydroformylation.
AB  - The first highly regioselective and general osmium-catalyzed hydroformylation of
      olefins to aldehydes is reported. The combination of Os3(CO)12 and imidazoyl
      substituted phosphine ligands allows n-selective (up to 99%) hydroformylation of
      bulk aliphatic as well as functional alkenes in good yields (64-87%). 

PMID- 25620414
TI  - Dark chocolate consumption and lower HbA1c in children with diabetes: Direct
      cause or pure happiness?

PMID- 25620410
TI  - Quantum dots for quantitative imaging: from single molecules to tissue.
AB  - Since their introduction to biological imaging, quantum dots (QDs) have
      progressed from a little known, but attractive, technology to one that has gained
      broad application in many areas of biology. The versatile properties of these
      fluorescent nanoparticles have allowed investigators to conduct biological
      studies with extended spatiotemporal capabilities that were previously not
      possible. In this review, we focus on QD applications that provide enhanced
      quantitative information concerning protein dynamics and localization, including
      single particle tracking and immunohistochemistry, and finish by examining the
      prospects of upcoming applications, such as correlative light and electron
      microscopy and super-resolution. Advances in single molecule imaging, including
      multi-color and three-dimensional QD tracking, have provided new insights into
      the mechanisms of cell signaling and protein trafficking. New forms of QD
      tracking in vivo have allowed the observation of biological processes at
      molecular level resolution in the physiological context of the whole animal.
      Further methodological development of multiplexed QD-based immunohistochemistry
      assays should enable more quantitative analysis of key proteins in tissue
      samples. These advances highlight the unique quantitative data sets that QDs can
      provide to further our understanding of biological and disease processes. 

PMID- 25620415
TI  - Micro- and nanogels with labile crosslinks - from synthesis to biomedical
      applications.
AB  - Micro- or nanosized three-dimensional crosslinked polymeric networks have been
      designed and described for various biomedical applications, including living cell
      encapsulation, tissue engineering, and stimuli responsive controlled delivery of
      bioactive molecules. For most of these applications, it is necessary to
      disintegrate the artificial scaffold into nontoxic residues with smaller
      dimensions to ensure renal clearance for better biocompatibility of the
      functional materials. This can be achieved by introducing stimuli-cleavable
      linkages into the scaffold structures. pH, enzyme, and redox potential are the
      most frequently used biological stimuli. Moreover, some external stimuli, for
      example light and additives, are also used to trigger the disintegration of the
      carriers or their assembly. In this review, we highlight the recent progress in
      various chemical and physical methods for synthesizing and crosslinking micro-
      and nanogels, as well as their development for incorporation of cleavable
      linkages into the network of micro- and nanogels. 

PMID- 25620417
TI  - Electrophysiological analysis of neuromuscular synaptic function in myasthenia
      gravis patients and animal models.
AB  - Study of the electrophysiological function of the neuromuscular junction (NMJ) is
      instrumental in the understanding of the symptoms and pathophysiology of
      myasthenia gravis (MG), an autoimmune disorder characterized by fluctuating and
      fatigable muscle weakness. Most patients have autoantibodies to the acetylcholine
      receptor at the NMJ. However, in recent years autoantibodies to other crucial
      postsynaptic membrane proteins have been found in previously 'seronegative' MG
      patients. Electromyographical recording of compound and single-fibre muscle
      action potentials provides a crucial in vivo method to determine neuromuscular
      transmission failure while ex vivo (miniature) endplate potential recordings can
      reveal the precise synaptic impairment. Here we will review these
      electrophysiological methods used to assess NMJ function and discuss their
      application and typical results found in the diagnostic and experimental study of
      patients and animal models of the several forms of MG. 

PMID- 25620418
TI  - Anthryl-1,2,4-oxadiazole-substituted calix[4]arenes as highly selective
      fluorescent chemodosimeters for Fe(3+).
AB  - Fluorescent chemosensors 1 and 2, with 1,2,4-oxadiazoles as the binding ligands
      and anthracene as the fluorophore, were synthesized through sequential 1,3
      dipolar cycloaddition reactions of 25,27-dioxyacetonitrilecalix[4]arenes 8 and
      11. The fluorescence of 1 was severely quenched by both Fe(3+) and Cu(2+) ,
      whereas that of 2 was selectively quenched only by Fe(3+) . Control compound 4
      was also selectively quenched by Fe(3+) , which implied the importance of anthryl
      1,2,4-oxadiazole core; furthermore, it was shown to give various oxidation
      products such as oxanthrone 13, anthraquinone 14, and imidazolyl oxanthrone 15.
      In addition to product separation and identification, the fluorescent quenching
      mechanism of these 9-anthryl-1,2,4-oxadiazolyl derivatives by Fe(3+) is also
      discussed. Furthermore, it should be noted that the oxadiazole-substituted
      anthracene 4 and calix[4]arene 2 are Fe(3+) -selective fluorescent
      chemodosimeters without the interference by Cu(2+) . 

PMID- 25620416
TI  - Ethanol deregulates Mecp2/MeCP2 in differentiating neural stem cells via
      interplay between 5-methylcytosine and 5-hydroxymethylcytosine at the Mecp2
      regulatory elements.
AB  - Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in the
      brain. MeCP2 expression is affected by different environmental insults including
      alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2
      expression in ethanol exposure-induced neurological symptoms. However, the
      underlying molecular mechanisms of ethanol-induced MeCP2 deregulation remain
      elusive. To study the effect of ethanol on Mecp2/MeCP2 expression during
      neurodifferentiation, we established an in vitro model of ethanol exposure, using
      differentiating embryonic brain-derived neural stem cells (NSC). Previously, we
      demonstrated the impact of DNA methylation at the Mecp2 regulatory elements (REs)
      on Mecp2/MeCP2 expression in vitro and in vivo. Here, we studied whether altered
      DNA methylation at these REs is associated with the Mecp2/MeCP2 misexpression
      induced by ethanol. Binge-like and continuous ethanol exposure upregulated
      Mecp2/MeCP2, while ethanol withdrawal downregulated its expression. DNA
      methylation analysis by methylated DNA immunoprecipitation indicated that
      increased 5-hydroxymethylcytosine (5hmC) and decreased 5-methylcytosine (5mC)
      enrichment at specific REs were associated with upregulated Mecp2/MeCP2 following
      continuous ethanol exposure. The reduced Mecp2/MeCP2 expression upon ethanol
      withdrawal was associated with reduced 5hmC and increased 5mC enrichment at these
      REs. Moreover, ethanol altered global DNA methylation (5mC and 5hmC). Under the
      tested conditions, ethanol had minimal effects on NSC cell fate commitment, but
      caused changes in neuronal morphology and glial cell size. Taken together, our
      data represent an epigenetic mechanism for ethanol-mediated misexpression of
      Mecp2/MeCP2 in differentiating embryonic brain cells. We also show the potential
      role of DNA methylation and MeCP2 in alcohol-related neurological disorders,
      specifically Fetal Alcohol Spectrum Disorders. 

PMID- 25620419
TI  - Computational prediction for emission energy of iridium (III) complexes based on
      TDDFT calculations using exchange-correlation functionals containing various HF
      exchange percentages.
AB  - The accurate prediction for the emission energies of the phosphorescent Ir (III)
      complexes is very useful for the realizing of full-color displays and large-area
      solid-state lighting in OLED fields. Quantum chemistry calculations based on
      TDDFT methods are most widely used to directly compute the triplet vertical
      excitation energies, yet sometimes the universality of these calculations can be
      limited because of the lack of experimental data for the relative family of
      structural analogues. In this letter, 16 literature emission energies at low
      temperature are linearly correlated with their theoretical values computed by
      TDDFT using exchange-correlation functionals containing various HF exchange
      percentage with the relation of E exp (em)  = 1.2E calc (em). The relation is
      proven to be robust across a wide range of structures for Ir (III) complexes.
      These theoretical studies should be expected to provide some guides for the
      design and synthesis of efficient emitting materials.

PMID- 25620420
TI  - One lithium atom binding with P-nitroaniline: lithium salts or lithium
      electrides?
AB  - Recently, both lithium (Li) salts and Li electrides formed by one Li atom
      interacting with ligand complexes, have been widely investigated. An interesting
      question emerges: is the configuration of one Li atom interacting with ligand
      complexes a Li salt or electride? In the present work, four configurations n-Li
      PNA (n = 1-4) were obtained by binding one Li atom with the p-nitroaniline (PNA)
      at different positions to explore this question. The results show that 1-Li-PNA
      and 2-Li-PNA are typical Li salts, and 4-Li-PNA is a typical Li electride.
      Significantly, 3-Li-PNA possesses both characteristics of Li salt and electride.
      At the same time, 3-Li-PNA has the largest first hyperpolarizability (2.9 * 10(6)
      au) by ROMP2 method compared with the other three configurations. Furthermore,
      the first hyperpolarizability of 3-Li-PNA is about 2600 times larger than that of
      PNA. Further, the vertical ionization potential (VIP) and interaction energy (E
      int) indicate that 3-Li-PNA is less stable than 1-Li-PNA and 2-Li-PNA (Li salts),
      but is more stable than 4-Li-PNA (Li electrides). 

PMID- 25620421
TI  - Computational study of interaction of alkali metals with C3N nanotubes.
AB  - Interaction of the alkali metals (AMs) like lithium (Li), sodium (Na), and
      potassium (K) with defective and non-defective (8,0) C3N nanotubes (C3NNT) have
      been investigated using the first-principles study. In addition to structural
      properties, we have also studied the electronic properties, charge transfer, and
      work function of the AM-C3NNT complexes. AMs are adsorbed on hollow sites,
      regardless of the initial positions. Upon the adsorption of AMs, the structures
      exhibit semiconducting behavior. Furthermore, interaction of Li atom can be
      explained by Dewar model, whereas for the other atoms there are different
      explanations. For all metal adsorbates, the direction of the charge transfer is
      from adsorbate to adsorbent, because of their high surface reactivity. The
      results showed that the nanotube with carbon vacancy is the most favorite
      adsorbent. Our findings also indicated that the enhancement in absolute
      adsorption energy is in order of Li > K > Na. It is noteworthy that clustering of
      AM atoms on the nanotubes with and without defects is not expected. It is worthy
      that C3NNT is a better adsorbent for AM atoms than CNT, graphene, C60, and B80. 

PMID- 25620422
TI  - Theoretical predictions of thermodynamic parameters of adsorption of nitrogen
      containing environmental contaminants on kaolinite.
AB  - In this study thermodynamic parameters of adsorption of nitrogen containing
      environmental contaminants (NCCs, 2,4,6, trinitrotoluene (TNT), 2,4
      dinitrotoluene (DNT), 2,4-dinitroanisole (DNAN), and 3-one-1,2,4-triazol-5-one
      (NTO)) interacting with the tetrahedral and octahedral surfaces of kaolinite were
      predicted. Adsorption complexes were investigated using a density functional
      theory and both periodic and cluster approach. The complexes, modeled using the
      periodic boundary conditions approach, were fully optimized at the BLYP-D2 level
      to obtain the structures and adsorption energies. The relaxed kaolinite-NCCs
      structures were used to prepare cluster models to calculate thermodynamic
      parameters and partition coefficients at the M06-2X-D3 and BLYP-D2 levels from
      the gas phase. The entropy effect on the Gibbs free energies of adsorption of
      NCCS on kaolinite was also studied and compared with available experimental data.
      The results showed that in all calculated models, the NCCs molecules are
      physisorbed and they favor a parallel orientation toward both kaolinite surfaces.
      It was found that all calculated NCCs compounds are more stable on the octahedral
      than on the tetrahedral surface of kaolinite. The Gibbs free energies and
      partition coefficients were also predicted for interactions of NCCs with Na
      kaolinite from aqueous solution. Calculations revealed adsorption of NCCs is
      effective from the gas phase on both cation free kaolinite surfaces and on Na
      kaolinite from aqueous solution at room temperature. Theoretical data were
      validated against experimental results, and the reasons for small differences
      between calculated and measured partition coefficients are discussed. 

PMID- 25620424
TI  - Can systems biology help to separate evolutionary analogies (convergent
      homoplasies) from homologies?
AB  - Convergent evolutionary analogies (homoplasies) of many kinds occur in diverse
      phylogenetic clades/lineages on both the animal and plant branches of the Tree of
      Life. Living organisms whose last common ancestors lived millions to hundreds of
      millions of years ago have later converged morphologically, behaviorally or at
      other levels of functionality (from molecular genetics through biochemistry,
      physiology and other organismic processes) as a result of long term strong
      natural selection that has constrained and channeled evolutionary processes. This
      happens most often when organisms belonging to different clades occupy ecological
      niches, habitats or environments sharing major characteristics that select for a
      relatively narrow range of organismic properties. Systems biology, broadly
      defined, provides theoretical and methodological approaches that are beginning to
      make it possible to answer a perennial evolutionary biological question relating
      to convergent homoplasies: Are at least some of the apparent analogies actually
      unrecognized homologies? This review provides an overview of the current state of
      knowledge of important aspects of this topic area. It also provides a resource
      describing many homoplasies that may be fruitful subjects for systems biological
      research. 

PMID- 25620423
TI  - Atomistic insights into the lung cancer-associated L755P mutation in HER2
      resistance to lapatinib: a molecular dynamics study.
AB  - HER2, a member of the human ErbB protein family belonging to receptor tyrosine
      kinases, plays important roles in regulating crucial cellular processes,
      including cell migration, proliferation, and differentiation. A missense
      mutation, L755P, in the HER2 kinase domain has been involved in lung cancer in
      humans and exhibits reduced response to lapatinib therapy. However, the detailed
      mechanism of how the HER2 L755P mutation causes drug resistance to lapatinib
      remains elusive. Here, molecular docking, molecular dynamics (MD) simulations,
      binding free energy calculations [molecular mechanics and generalized
      Born/surface area (MM-GBSA)] were performed to reveal the mechanism of drug
      resistance due to the HER2 L755P mutation. MD simulations revealed that the L755P
      mutation caused structural changes in the regions of helix alphaC, the glycine
      rich loop, and the activation loop, thereby leading to the loss of interactions
      between the solubilizing group of lapatinib and HER2. Moreover, MM-GBSA
      calculations suggested that hydrophobic interactions between lapatinib and HER2
      contribute most to the binding affinity, and that the L755P mutation could result
      in a less energetically favorable HER2/lapatinib complex. This may weaken the
      binding of lapatinib to the mutated HER2, thereby leading to the emergence of
      drug resistance. This study offers a structural explanation for the effect of the
      L755P mutation on the HER2/lapatinib complex. 

PMID- 25620425
TI  - The impact of dietary fibers on dendritic cell responses in vitro is dependent on
      the differential effects of the fibers on intestinal epithelial cells.
AB  - SCOPE: In the present study, the direct interaction of commonly consumed fibers
      with epithelial or dendritic cells (DCs) was studied. METHODS AND RESULTS: The
      fibers were characterized for their sugar composition and chain length profile.
      When in direct contact, fibers activate DCs only mildly. This was different when
      DCs and fibers were co-cultured together with supernatants from human epithelial
      cells (Caco spent medium). Caco spent medium enhanced the production of IL-12, IL
      1Ra, IL-6, IL-8, TNF-alpha, MCP-1 (monocyte chemotactic protein), and MIP-1alpha
      but this was strongly attenuated by the dietary fibers. This attenuating effect
      on proinflammatory cytokines was dependent on the interaction of the fibers with
      Toll-like receptors as it was reduced by Pepinh-myd88. The interaction of galacto
      oligosaccharides, chicory inulin, wheat arabinoxylan, barley beta-glucan with
      epithelial cells and DCs led to changes in the production of the Th1 cytokines in
      autologous T cells, while chicory inulin, and barley beta-glucan reduced the Th2
      cytokine IL-6. The Treg-promoting cytokine IL-10 was induced by galacto
      oligosaccharides whereas chicory inulin decreased the IL-10 production.
      CONCLUSIONS: Our results suggest that dietary fibers can modulate the host immune
      system not only by the recognized mechanism of effects on microbiota but also by
      direct interaction with the consumer's mucosa. This modulation is dietary fiber
      type dependent.

PMID- 25620426
TI  - Psychosocial interventions in the treatment of youth diagnosed or at high-risk
      for pediatric bipolar disorder: A review of the literature.
AB  - Pediatric bipolar disorder (PBD) has emerged as a research field in which
      psychosocial treatments have provided a plethora of empirical findings over the
      last decade. We addressed this issue through a systematic review aimed of
      establishing their effectiveness and feasibility as adjunctive therapies for
      youth with PBD or at high-risk for PBD. A comprehensive search of databases was
      performed between 1990 and September 2014. Overall, 33 studies were specifically
      related to the issue and 20 of them were original articles. Evidence suggests
      that both "multi-family psychoeducational psychotherapy' and "family-focused
      therapy" are possible effective treatments for PBD. Likewise, "child and family
      focused cognitive-behavioral therapy" may be characterized as a treatment in its
      experimental phase. The remaining therapies fail to obtain enough empirical
      support due to inconsistent findings among clinical trials or data solely based
      on case reports. Studies of psychosocial treatments provide concluding results
      concerning their feasibility and acceptability. Larger sample sizes and more
      randomized controlled trials are mandatory for diminishing methodological
      shortcomings encountered in the treatments displayed.

PMID- 25620428
TI  - The diagnostic criteria for allergic bronchopulmonary aspergillosis in children
      with poorly controlled asthma need to be re-evaluated.
AB  - AIM: The aim of this study was to examine the association between allergic
      bronchopulmonary aspergillosis (ABPA) and poorly controlled asthma in children
      and appraise the diagnostic criteria. METHODS: The study included 100 children
      with poorly controlled asthma. We diagnosed ABPA using the Aspergillus skin test,
      pulmonary function test, total and specific immunoglobulin E (IgE) to Aspergillus
      fumigatus, chest radiograph and high-resolution computed tomography. Patients
      were diagnosed and classified according to the Rosenberg-Patterson criteria for
      ABPA. The cut-off value for total serum IgE was calculated by receiver operating
      characteristics curve analysis. RESULTS: Of 100 children with poorly controlled
      asthma, 26 patients were ABPA positive. There was a significant difference in the
      forced expiratory volume in 1-sec/forced vital capacity ratio between ABPA
      positive (0.78 +/- 0.14) and negative (0.87 +/- 0.15) children (p = 0.008). ABPA
      positive children were categorised as seropositive, central bronchiectasis and
      other radiological findings. The receiver operating characteristics curve was
      constructed, and a value of 1200 IU/mL of total IgE was observed, with 88.5%
      sensitivity and 70.5% specificity. CONCLUSION: This study showed an association
      between ABPA and poorly controlled asthma in children and suggests a higher cut
      off value of total IgE for the diagnosis of ABPA.

PMID- 25620427
TI  - Loss of hepatic chaperone-mediated autophagy accelerates proteostasis failure in
      aging.
AB  - Chaperone-mediated autophagy (CMA), a cellular process that contributes to
      protein quality control through targeting of a subset of cytosolic proteins to
      lysosomes for degradation, undergoes a functional decline with age. We have used
      a mouse model with liver-specific defective CMA to identify changes in
      proteostasis attributable to reduced CMA activity in this organ with age. We have
      found that other proteolytic systems compensate for CMA loss in young mice which
      helps to preserve proteostasis. However, these compensatory responses are not
      sufficient for protection against proteotoxicity induced by stress (oxidative
      stress, lipid challenges) or associated with aging. Livers from old mice with CMA
      blockage exhibit altered protein homeostasis, enhanced susceptibility to
      oxidative stress and hepatic dysfunction manifested by a diminished ability to
      metabolize drugs, and a worsening of the metabolic dysregulation identified in
      young mice. Our study reveals that while the regulatory function of CMA cannot be
      compensated for in young organisms, its contribution to protein homeostasis can
      be handled by other proteolytic systems. However, the decline in the compensatory
      ability identified with age explains the more severe consequences of CMA
      impairment in older organisms and the contribution of CMA malfunction to the
      gradual decline in proteostasis and stress resistance observed during aging. 

PMID- 25620429
TI  - Reply to reflection on MUNE.

PMID- 25620430
TI  - How do pregnant women manage lumbopelvic pain? Pain management and their
      perceived effectiveness.
AB  - AIMS AND OBJECTIVES: This study aims to (1) investigate the pain management
      treatments used by pregnant women with lumbopelvic pain and their perceived
      effectiveness and (2) identify the predictors of pain treatment use. BACKGROUND:
      A variety of treatments have been shown to be effective for reducing pregnancy
      related lumbopelvic pain. However, the frequency of use of pain treatments and
      their perceived efficacy in pregnant women is still unknown. Knowledge regarding
      the use and perceived efficacy of these treatments would help guide clinical
      practice and inform future research. DESIGN: A cross-sectional design with
      consecutive sampling. METHODS: Participants were pregnant women in the 35th to
      40th gestational week who reported lumbopelvic pain in an antenatal clinic of a
      medical centre in Taiwan. Questionnaires were administered assessing pain
      treatment use, pain relief associated with each treatment (e.g. perceived
      effectiveness), pain intensity, pain interference, pain endurance beliefs and
      demographic variables. RESULTS: Among 295 participants with lumbopelvic pain,
      only 34 (12%) sought pain treatment. The pain management treatments used included
      mechanical treatments (80% = 27/34), herbal medicine (9% = 3/34), exercise (6% =
      2/34) and medications (6% = 2/34). Average perceived effectiveness associated
      with the treatments was 55%. Use of pain management strategies was negatively
      associated with pain endurance beliefs, but not with pain intensity or pain
      interference. CONCLUSIONS: Pregnant women with lumbopelvic pain are unlikely to
      seek or use pain management treatments for pain, suggesting a greater need for
      adopting effective pain treatment in clinical settings. RELEVANCE TO CLINICAL
      PRACTICE: The study contributes new knowledge regarding how pregnant women cope
      with lumbopelvic pain and reveals very low rates in the use of pain treatments.
      Health professionals should assess pregnant women's pain beliefs about pain
      endurance and emphasise the safety and effectiveness of interventions that have
      empirical support, to help minimise unnecessary pain during pregnancy.

PMID- 25620432
TI  - States variations in the provision of bariatric surgery under Affordable Care Act
      exchanges.
AB  - The Affordable Care Act (ACA) attempts to reduce healthcare costs while
      simultaneously providing the means for more Americans to obtain health insurance.
      Among other things, the ACA expands preventative care for obesity by mandating
      screening and counseling. However, it permits the states to determine whether to
      mandate treatments for inclusion in plans offered on the state-run exchanges.
      Bariatric surgery is a highly cost-effective treatment for obesity, yet states
      have taken varying stances on whether to mandate its inclusion. In light of the
      rising cost of obesity and resulting burden placed on the federal government and
      the economy, this article advocates a comparable mandatory inclusion of bariatric
      surgery in all plans offered on state and federally run exchanges. 

PMID- 25620433
TI  - Bariatric surgery and risk of postoperative endometrial cancer: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Bariatric surgery is an essential intervention for severely obese
      patients who fail medical treatment. It has been linked to improvements in
      cardiovascular and cerebrovascular disease. However, its effect on endometrial
      cancer risk is still unknown. This is a systematic review and meta-analysis of
      available studies on bariatric surgery and risk of postoperative endometrial
      cancer. The objective of this study was to explore the association between
      bariatric surgery and endometrial cancer risk. METHODS: A comprehensive search of
      the databases of PubMed/MEDLINE, EMBASE, and CENTRAL was performed from their
      dates of inception to July 2014. The inclusion criterion was articles on
      bariatric surgery and incidence of endometrial cancer after the procedure. Two
      authors independently assessed the quality of the articles and extracted the
      data. RESULTS: From 159 full-text articles, 6 observational studies met the
      inclusion criterion, and 3 studies involving 890,110 participants were included
      in the meta-analysis based on the random effects model. There was a reduced risk
      of endometrial cancer postoperatively in those receiving bariatric surgery
      compared with controls with pooled relative risk = .40 (95% CI: .20-.79).
      CONCLUSIONS: Bariatric surgery is associated with a reduced risk of endometrial
      cancer after the procedure. However, more randomized controlled studies are
      needed to provide better quality of evidence.

PMID- 25620434
TI  - Has mini gastric bypass come of age?

PMID- 25620435
TI  - Predictors of a successful medical weight loss program.
AB  - BACKGROUND: Many practices are creating weight loss programs, in preparation for
      bariatric surgery or for patients who wish to lose weight without surgery.
      Preoperative weight loss may be associated with improved postoperative weight
      loss and resolution of co-morbidities. The aim of this study is to investigate
      the success of a preoperative weight loss program at a single institution and the
      variables associated with success in weight loss. METHODS: We enrolled patients
      in a once monthly multidisciplinary preoperative weight loss program and
      evaluated % total weight lost over the 6-month program for primary and for
      revisional bariatric surgical patients. Demographic characteristics, weight,
      program related factors, and co-morbidities were recorded. One-way ANOVA and
      multiple linear regression models were carried out to assess variables. Parameter
      estimates of multiple linear regression models were reported. Statistical
      significance was set at .05 and analysis was done using SAS 9.3. RESULTS: A total
      of 133 patients enrolled and completed the program over a period of 14 months.
      Only 50.8% of the patients lost weight with average weight loss of .1+/-4.0 lbs.
      Patient's sex, insurance, psychiatric history, co-morbidities, referral status,
      or type of counseling had no significant effect on weight loss (P>.05). Patients
      between 30 and 50 years old on average were more successful in losing weight (P =
      .018). Patients considering revisional surgery were less successful
      preoperatively compared to first time candidates (P = .0007). CONCLUSION:
      Patients between 30 and 50 years of age, first time surgical candidates, and
      those with higher weights may be more successful in losing weight in a
      preoperative bariatric weight loss program.

PMID- 25620436
TI  - The EFFORT trial: Preoperative enoxaparin versus postoperative fondaparinux for
      thromboprophylaxis in bariatric surgical patients: a randomized double-blind
      pilot trial.
AB  - BACKGROUND: Prophylaxis for venous thromboembolism is routinely performed for all
      patients undergoing bariatric surgery. However, there is disagreement regarding
      the optimal dosing and duration of anticoagulant therapy. Furthermore, there is
      little data regarding the incidence of asymptomatic deep venous thrombosis (DVT)
      in this population. Our objective was to conduct a pilot randomized double blind
      study to evaluate the pharmacodynamic parameters of 2 different anticoagulation
      medications (enoxaparin and fondaparinux) administered to patients undergoing
      bariatric surgery. METHODS: From July 2010 to August 2013, 198 consecutive
      bariatric surgery patients from an academic institution were randomized in a
      double blinded manner to receive either 40 mg enoxaparin twice daily or 5mg
      fondaparinux sodium once daily. Antifactor Xa activity was measured on all
      patients in both study arms, 3 hours after the first dose (on the day of the
      operation), immediately before the second dose (postoperative day one), and 3
      hours after the second dose. At the routine 2 week postoperative visit, patients
      underwent magnetic resonance venography (MRV) to detect DVT. The primary outcome
      was attainment of therapeutic antifactor Xa levels. The secondary outcome was
      DVT, as detected by MRV. Safety outcomes were perioperative bleeding,
      perioperative complications, and death. RESULTS: Of 198 patients randomized, 177
      underwent MRV and 137 had interpretable antifactor Xa levels. Nearly half of the
      patients (47.4%) did not attain target prophylactic antifactor Xa levels.
      Adequate antifactor Xa levels were more common with fondaparinux (74.2%) than
      with enoxaparin (32.4%). Antifactor Xa levels were also associated with
      preoperative D-dimer level. 4 of the 175 patients who underwent MRV developed
      DVT, 2 in each arm of the study. No major adverse events occurred in either arm.
      CONCLUSION: Fondaparinux was much more likely to produce target prophylactic
      antifactor Xa levels than enoxaparin. Both regimens appear to be equally
      effective at reducing the risk of DVT. Further prospective studies are needed to
      determine the optimal DVT prophylaxis regimen in the bariatric surgical
      population.

PMID- 25620437
TI  - Case review and consideration for imaging and work evaluation of the pregnant
      bariatric patient.
AB  - BACKGROUND: There is an increasing trend toward morbid obesity in women of
      childbearing age and a subsequent increase in number of weight reduction
      surgeries in these individuals. As a result, special attention needs to be paid
      to potential postsurgical complications during pregnancy, particularly after Roux
      en-Y gastric bypass (RYGB). We are presenting our small case series and our
      suggestions for management for the pregnant bariatric patient. The aim of this
      study is to review our institutional experience and present our algorithm to
      approach pregnant women presenting with abdominal pain and/or emesis after RYGB.
      METHODS: After Institutional Review Board approval, a retrospective chart review
      was performed at a single center institution between 2010 and 2013. Data
      regarding clinical presentation, physical exam findings, laboratory values,
      radiographic studies, intraoperative findings, and clinical outcomes of both
      mother and fetus were collected and reviewed for pregnant patients with history
      of RYGB and abdominal distress. RESULTS: Five patients were identified. Patient
      age ranged from 22-34 years (mean 28.4). Gestational age ranged from 9-31 months
      (mean 19.2). Average body mass index at presentation was 30.3 kg/m(2). Of the 5
      patients, 4 presented with abdominal pain and one with intractable emesis. Four
      patients were taken to the operating room. One was successfully discharged. Two
      of the patients had an obstruction from adhesions, and the other 2 were found to
      have internal hernia. There was no mortality for either fetus or mother. One
      patient required premature delivery at 28 weeks. CONCLUSIONS: Pregnant women with
      history of RYGB who present with abdominal pain should be evaluated urgently for
      internal hernia or obstruction. A systematic approach is needed to ensure prompt
      diagnosis.

PMID- 25620438
TI  - Separation of aromatic solvents from oil refinery reformates by a newly designed
      ionic liquid using gas chromatography with flame ionization detection.
AB  - The aim of this study was to determine whether the new ionic liquid, N,N-dimethyl
      2-oxopyrrolidonium iodide, synthesized in our laboratory is a suitable solvent
      for the separation of aromatic components benzene, toluene, ethylbenzene, and
      xylenes from petroleum mixtures (reformates) in liquid-liquid extraction. In
      pursuance of the above aim, a method to extract all components of a mixture,
      containing four aromatic components simultaneously, was developed. A new ionic
      liquid and a previously used liquid were compared for their extraction abilities.
      These ionic liquids were, respectively, N,N-dimethyl-2-oxopyrrolidinium iodide
      and 1-ethyl-3-methyl imidazolium ethyl sulfate. The concentrations of each
      benzene, toluene, ethylbenzene, and xylenes component in the extract and
      raffinate phases were measured by gas chromatography with flame ionization
      detection as volume percent to determine the extraction ability of the ionic
      liquids. The results obtained for both the reformate samples and model mixtures
      indicated that the new ionic liquid was effective as an extracting solvent for
      the recovery of aromatic components from reformates. Also the analysis results,
      using gas chromatography with flame ionization detection, for the reformate
      samples were as good as the results obtained by a local oil refinery. The
      extraction results also show that the developed method is very suitable for the
      separation and analysis of aromatic components in reformates. 

PMID- 25620440
TI  - An introduction to patient-reported outcome measures (PROMs) in physiotherapy.
AB  - The use of patient-reported outcome measures (PROMs) is set to rise in
      physiotherapy. PROMs provide additional 'patient-centred' data which is unique in
      capturing the patient's own opinion on the impact of their disease or disorder,
      and its treatment, on their life. Thus, PROMs are increasingly used by clinicians
      to guide routine patient care, or for the purposes of audit, and are already
      firmly embedded in clinical research. This article seeks to summarise the key
      aspects of PROM use for physiotherapists, both in routine clinical practice and
      in the research setting, and highlights recent developments in the field. Generic
      and condition-specific PROMs are defined and examples of commonly used measures
      are provided. The selection of appropriate PROMs, and their effective use in the
      clinical and research settings is discussed. Finally, existing barriers to PROM
      use in practice are identified and recent physiotherapy PROM initiatives, led by
      the Royal Dutch Society for Physical Therapy are explored. 

PMID- 25620439
TI  - Effects of eliminating drug caps on racial differences in antidepressant use
      among dual enrollees with diabetes and depression.
AB  - PURPOSE: Black patients with diabetes are at greater risk of underuse of
      antidepressants even when they have equal access to health insurance. This study
      aimed to evaluate the impact of removing a significant financial barrier to
      prescription medications (drug caps) on existing black-white disparities in
      antidepressant treatment rates among patients with diabetes and comorbid
      depression. METHODS: We used an interrupted time series with comparison series
      design and a 5% representative sample of all fee-for-service Medicare and
      Medicaid dual enrollees to evaluate the removal of drug caps on monthly
      antidepressant treatment rates. We evaluated the impact of drug cap removal on
      racial gaps in treatment by modeling the month-to-month white-black difference in
      use within age strata (younger than 65 years of age or 65 years of age or older).
      We compared adult dual enrollees with diabetes and comorbid depression living in
      states with strict drug caps (n = 221) and those without drug caps (n = 1133)
      before the policy change. Our primary outcome measures were the proportion of
      patients with any antidepressant use per month and the mean standardized monthly
      doses (SMDs) of antidepressants per month. FINDINGS: The removal of drug caps in
      strict drug cap states was associated with a sudden increase in the proportion of
      patients treated for depression (4 percentage points; 95% CI, 0.03-0.05, P <
      0.0001) and in the intensity of antidepressant use (SMD: 0.05; 95% CI, 0.03-0.07,
      P < 0.001). Although antidepressant treatment rates increased for both white and
      black patients, the white-black treatment gap increased immediately after Part D
      (0.04 percentage points; 95% CI, 0.01-0.08) and grew over time (0.04 percentage
      points per month; 95% CI, 0.002-0.01; P < 0.001). IMPLICATIONS: Policies that
      remove financial barriers to medications may increase depression treatment rates
      among patients with diabetes overall while exacerbating treatment disparities.
      Tailored outreach may be needed to address nonfinancial barriers to mental health
      services use among black patients with diabetes.

PMID- 25620442
TI  - Transdermal delivery of forskolin from emulsions differing in droplet size.
AB  - The skin permeation of forskolin, a diterpene isolated from Coleus forsholii, was
      studied using oil in water (O/W) emulsions as delivery formulations and also an
      oil solution for comparative purposes. Two forskolin-loaded emulsions of
      water/Brij 72:Symperonic A7/Miglyol 812:Isohexadecane, at 0.075 wt% forskolin
      concentration were prepared with the same composition and only differing in
      droplet size (0.38 MUm and 10 MUm). The emulsions showed high kinetic stability
      at 25  degrees C. In vitro study of forskolin penetration through human skin was
      carried out using the MicroettePlus((r)) system. The concentration of the active
      in the receptor solution (i.e. ethanol/phosphate buffer 40/60, v/v) was analyzed
      by high performance liquid chromatography with UV detection. The obtained results
      showed that forskolin permeation from the emulsions and the oil solution, through
      human skin, was very high (up to 72.10%), and no effect of droplet size was
      observed.

PMID- 25620443
TI  - Assessment of surfactants for efficient droplet PCR in mineral oil using the
      pendant drop technique.
AB  - Amplification and detection of nucleic acid sequences within integrated
      microsystems is routinely conducted using the technique of droplet PCR, wherein
      the polymerase chain reaction (PCR) is performed in microscale water-in-oil
      droplets (nanoliter to picoliter volumes). During droplet PCR, interactions at
      the interface of the droplet tend to dominate. Specifically, adsorption of the
      polymerase at the droplet interface leads to inefficient amplification. To reduce
      polymerase adsorption, surfactants such as the silicone-based ABIL EM90 have been
      commonly used. However, these surfactants have been selected largely through
      trial and error, and have been only somewhat effective. For example, when using
      ABIL EM90, 8 times (8 *) the manufacturer prescribed concentration of polymerase
      was necessary for amplification. In this report, we use the pendant drop
      technique to measure adsorption and loss of enzyme at droplet interfaces for
      various surfactant-oil combinations. Dynamic interfacial tension and surface
      pressure measurements showed that significant polymerase adsorption occurs when
      using ABIL EM90. In contrast, much lower polymerase adsorption is observed when
      using Brij L4, a nonionic surfactant with a C12 tail and an oxyethylene
      headgroup, which has not yet been reported for droplet PCR. These results
      correlate strongly with droplet PCR efficiency. Brij L4 enables highly efficient
      PCR at 2 * polymerase concentration, and still enables effective PCR at 1 *
      polymerase concentration. Overall, this work introduces a methodology for
      quantitatively assessing surfactants for use with droplet microreactors, and it
      demonstrates the practical value of this new approach by identifying a surfactant
      that can dramatically improve the efficiency of droplet PCR.

PMID- 25620444
TI  - Scanning electrochemical impedance microscopy for investigation of glucose
      oxidase catalyzed reaction.
AB  - In this research biointerface based on immobilized glucose oxidase (GOx) was
      evaluated by scanning electrochemical impedance microscopy (SEIM), which
      consisted of merged scanning electrochemical microscopy (SECM) and
      electrochemical impedance spectroscopy (EIS). The gluconolactone, which is
      quickly hydrolyzed to gluconic acid, is produced during the enzyme-catalyzed
      glucose oxidation reaction. Gluconic acid formed above an enzyme-modified not
      conducting plastic surface, was evaluated by EIS technique. A two electrode cell
      consisting of a scanning probe, which was based on 10 MUm diameter
      ultramicroelectrode and stationary platinum counter/reference electrode was
      applied for the measurement. Locally measured solution impedance depends on the
      gluconic acid concentration close to the ultramicroelectrode surface and on the
      ion diffusion, which is hindered when the electrode is approaching close to the
      GOx-modified surface. EIS results were evaluated by applying an equivalent
      circuit consisting of elements representing solution resistance, double-layer
      capacitance, charge-transfer resistance and Warburg impedance. Solution
      resistance was calculated and showed to be dependent on the position of
      ultramicroelectrode. Also it was observed that the thickness of the conducting
      layer and gluconic acid concentration both are changing in time. The results
      indicate that here proposed SEIM technique could become a valuable tool for the
      investigation and characterization of enzyme-modified surfaces of biosensors and
      biofuel cells.

PMID- 25620446
TI  - A configurational and conformational study of (-)-Oseltamivir using a multi
      chiroptical approach.
AB  - To better understand structure-activity relationship (SAR) results, closely
      related to the structural features of (-)-Oseltamivir, four chiroptical methods,
      i.e. electronic circular dichroism (ECD), optical rotatory dispersion (ORD),
      vibrational circular dichroism (VCD), and Raman optical activity (ROA), utilizing
      different solvents, were employed in an effort to discover a set of the most
      probable conformations. Such multi-chiroptical approaches supported by quantum
      chemical calculations pointed out that different conformers are stable in
      chloroform, acetonitrile and water solutions of (-)-Oseltamivir. In this way, the
      most probable structures responsible for reported SAR results were established
      for the first time. It turned out that one of the predominant conformers in a
      solution is in excellent agreement with the X-ray analysis derived solid-state
      structure determined for (-)-Oseltamivir phosphate. 

PMID- 25620445
TI  - DNA methyltransferase inhibition accelerates the immunomodulation and migration
      of human mesenchymal stem cells.
AB  - DNA methyltransferase (DNMT) inhibitors regulate target gene expression through
      epigenetic modifications, and these compounds have primarily been studied for
      cancer therapy or reprogramming. However, the effect of DNMT inhibitors on the
      immunomodulatory capacity of human mesenchymal stem cells (hMSCs) has not been
      investigated. In the present study, we treated hMSCs with 5-azacytidine (5-aza),
      a DNMT inhibitor, and confirmed that the inhibitory effects on mononuclear cell
      proliferation and cell migration toward activated T cells were increased. To
      identify the immunomodulatory factors stimulated through 5-aza treatment, we
      investigated the changes in promoter methylation patterns using methylation
      arrays and observed that the promoters of immunomodulatory factors, COX2 and
      PTGES, and migration-related factors, CXCR2 and CXCR4, were hypomethylated after
      5-aza treatment. In addition, we observed that the COX2-PGE2 pathway is one of
      the main pathways for the enhanced immunosuppressive activity of hMSCs through 5
      aza treatment. We also determined that the migration of hMSCs toward ligands for
      CXCR2/CXCR4 was increased after 5-aza treatment. Moreover, using an experimental
      colitis model, we showed that 5-aza pre-treatment could enhance the therapeutic
      effect of MSCs against immune-related diseases. 

PMID- 25620447
TI  - Interventions to prevent and reduce teen dating violence.

PMID- 25620448
TI  - Evaluation of the Start Strong initiative: preventing teen dating violence and
      promoting healthy relationships among middle school students.
AB  - PURPOSE: This study reports on an independent evaluation of Start Strong:
      Building Healthy Teen Relationships, a multicomponent initiative targeting 11- to
      14-year-olds. "Start Strong" was designed to focus on the developmental needs of
      middle school students and to enhance skills and attitudes consistent with
      promotion of healthy relationships and reduction of teen dating violence (TDV).
      METHODS: The quasi-experimental evaluation design included data collection from
      four Start Strong schools and four comparison schools. Student surveys were
      collected at four waves of data at the beginning and the end of grades 7 and 8.
      Multilevel models used repeated observations nested within students who were, in
      turn, nested within schools to determine whether participation in Start Strong
      enhanced healthy skills and relationships and decreased TDV-related attitudes and
      behaviors. RESULTS: Short-term effects from waves 1 to 2 were statistically
      significant for increased parent-child communication and boy/girlfriend
      relationship satisfaction and support and decreased gender stereotypes and
      attitudes supporting TDV. Findings for acceptance of TDV and gender stereotypes
      persisted longitudinally. CONCLUSIONS: Results are promising and illustrate that
      a multicomponent, community-based initiative reduced risk factors predictive of
      TDV. Start Strong is innovative in its focus on early adolescence, which is a
      critical period in the transition to dating. The results inform future
      intervention efforts and underscore the need for further study of middle school
      students.

PMID- 25620449
TI  - Effectiveness of "shifting boundaries" teen dating violence prevention program
      for subgroups of middle school students.
AB  - PURPOSE: We examine whether the Shifting Boundaries (SB) intervention, a primary
      intervention to prevent youth dating violence and sexual harassment (DV/H), is
      differentially effective for girls compared with boys or for youth with a history
      of DV/H experiences. METHODS: We randomly assigned SB to 30 public middle schools
      in New York City, enrolling 117 sixth and seventh grade classes to receive a
      classroom, building, combined, or neither intervention. The SB classroom
      intervention included six sessions emphasizing the laws/consequences of DV/H,
      establishing boundaries and safe relationships. The SB schoolwide/building
      intervention included the use of school-based restraining orders, greater
      faculty/security presence in unsafe "hot spots" mapped by students, and posters
      to increase DV/H awareness and reporting. Student surveys were implemented at
      baseline, immediately after intervention, and 6 months after intervention.
      RESULTS: At 6 months after intervention, the SB building-level intervention was
      associated with significant reductions in the frequency of sexual harassment (SH)
      perpetration and victimization; the prevalence and frequency of sexual dating
      violence victimization; and the frequency of total dating violence victimization
      and perpetration. We also had one anomalous finding that the interventions were
      associated with an increase in the prevalence of SH victimization. These results
      were consistent for girls and boys, and those with or without a history of DV/H,
      with the one exception for those exposed to the SB building condition who had
      earlier reported perpetrating SH had a significantly lower frequency of
      perpetrating SH at the follow-up than those without such a history. CONCLUSIONS:
      SB can provide effective universal prevention of middle school DV/H experiences,
      regardless of students' prior exposure histories, and for boys and girls.

PMID- 25620450
TI  - A latent transition model of the effects of a teen dating violence prevention
      initiative.
AB  - PURPOSE: Patterns of physical and psychological teen dating violence (TDV)
      perpetration, victimization, and related behaviors were examined with data from
      the evaluation of the Start Strong: Building Healthy Teen Relationships
      initiative, a dating violence primary prevention program targeting middle school
      students. METHODS: Latent class and latent transition models were used to
      estimate distinct patterns of TDV and related behaviors of bullying and sexual
      harassment in seventh grade students at baseline and to estimate transition
      probabilities from one pattern of behavior to another at the 1-year follow-up.
      Intervention effects were estimated by conditioning transitions on exposure to
      Start Strong. RESULTS: Latent class analyses suggested four classes best captured
      patterns of these interrelated behaviors. Classes were characterized by elevated
      perpetration and victimization on most behaviors (the multiproblem class),
      bullying perpetration/victimization and sexual harassment victimization (the
      bully-harassment victimization class), bullying perpetration/victimization and
      psychological TDV victimization (bully-psychological victimization), and
      experience of bully victimization (bully victimization). Latent transition models
      indicated greater stability of class membership in the comparison group.
      Intervention students were less likely to transition to the most problematic
      pattern and more likely to transition to the least problem class. CONCLUSIONS:
      Although Start Strong has not been found to significantly change TDV, alternative
      evaluation models may find important differences. Latent transition analysis
      models suggest positive intervention impact, especially for the transitions at
      the most and the least positive end of the spectrum.

PMID- 25620451
TI  - Building a culture of health: promoting healthy relationships and reducing teen
      dating violence.
AB  - Our society is faced with an epidemic of partner violence that has far-reaching
      consequences. As viewed through a public health lens, prevention of teen dating
      violence can thwart this epidemic from starting and spreading. The Robert Wood
      Johnson Foundation's Culture of Health strategy aims to reduce negative outcomes
      and promotes overall well-being. This supplement affirms our dedication to a
      Culture of Health by generating an evidence base to prevent teen dating violence
      and promote healthy relationships across the life span. 

PMID- 25620452
TI  - Testing two approaches to revictimization prevention among adolescent girls in
      the child welfare system.
AB  - PURPOSE: Girls in the child welfare system are at high risk of revictimization in
      adolescence. The present study compared two interventions designed to decrease
      revictimization in a diverse sample of adolescent child welfare-involved girls.
      The social learning/feminist (SL/F) intervention focused on concepts derived from
      social learning and feminist models of risk, such as sexism and beliefs about
      relationships. The risk detection/executive function (RD/EF) intervention focused
      on development of specific executive function abilities related to detecting and
      responding to risky situations/people. METHODS: Participants were randomized to
      RD/EF (n = 67) or SL/F intervention (n = 67). A group of youth (n = 42) engaged
      in the research assessments only. Participants (n = 180) were assessed before
      intervention, immediately after intervention, 2 months after intervention, and 6
      months after intervention. We examined revictimization (the presence/absence of
      sexual or physical assault in any relationship) over time. RESULTS: Adolescent
      girls in the RD/EF condition were nearly five times less likely to report sexual
      revictimization compared with girls in the no-treatment group. A trend suggested
      that girls who participated in the SL/F intervention were 2.5 times less likely
      to report sexual revictimization relative to the no-treatment group. For physical
      revictimization, the odds of not being physically revictimized were three times
      greater in the SL/F condition and two times greater in the RD/EF condition
      compared with the no-treatment group. CONCLUSIONS: The active interventions did
      not differ significantly from one another in rates of revictimization, suggesting
      that practitioners have at least two viable options to engage high-risk youth in
      revictimization prevention.

PMID- 25620453
TI  - Implementing a targeted teen dating abuse prevention program: challenges and
      successes experienced by expect respect facilitators.
AB  - PURPOSE: Expect Respect Support Groups (ERSGs) are a targeted 24-week dating
      abuse prevention program tailored to middle and high school students who have
      been exposed to violence. As part of a controlled evaluation, this qualitative
      study was designed to examine facilitators' experiences with program
      implementation and generate a deeper understanding of factors that enhance or
      challenge implementation and program outcomes. METHODS: Semistructured interviews
      with Expect Respect Support Group facilitators (three males and four females)
      were conducted at the midpoint and endpoint of the school year. Interview topics
      included working within the school system, strategies for establishing a
      productive group process, and individual- and group-level responses to the
      program. RESULTS: Facilitators indicated that school counselors' awareness of
      students' exposure to violence increased their ability to refer eligible
      students. Within a supportive school environment, successful groups harnessed the
      protective qualities of a positive peer group, supported members in questioning
      the normalcy of abuse, and provided opportunities for building healthy
      relationship skills. Challenges resulted from impediments to group cohesion
      including insufficient referrals, inconsistent attendance, and low levels of
      school support. Students who were frequently absent and disengaged from school
      were particularly challenging to engage in a school-based program. CONCLUSIONS:
      This research demonstrates that successful implementation of a targeted school
      based dating violence prevention program relies on building school support and
      awareness of teen dating violence, especially for appropriate identification and
      referral of at-risk students. High levels of school support enhance the
      development of a supportive group process and attitudinal and behavioral changes
      among participants.

PMID- 25620454
TI  - Prevalence of teen dating violence and co-occurring risk factors among middle
      school youth in high-risk urban communities.
AB  - PURPOSE: This study describes the lifetime prevalence of teen dating violence
      (TDV) perpetration in a sample of middle school students from high-risk urban
      communities and examines the relation between TDV and related cognitive and
      behavioral risk factors. METHODS: Surveys were administered to 2,895 middle
      school students in four U.S. cities; 1,673 students (58%) reported having dated
      and were included in analyses. The sample was 52.3% female, 48.2% non-Hispanic
      black/African-American, 38.2% Hispanic, 4.8% non-Hispanic white, and 7.6% other
      race. Six types of TDV perpetration were assessed: threatening behaviors,
      verbal/emotional abuse, relational abuse, physical abuse, sexual abuse, and
      stalking. RESULTS: Of the students who had dated, 77% reported perpetrating
      verbal/emotional abuse, 32% reported perpetrating physical abuse, 20% reported
      threatening a partner, 15% reported perpetrating sexual abuse, 13% reported
      perpetrating relational abuse, and 6% reported stalking. Girls were more likely
      than boys to report perpetrating threatening behaviors, verbal/emotional abuse,
      and physical abuse, and boys were more likely to report perpetrating sexual
      abuse. Involvement in bullying positively predicted perpetration of TDV, albeit,
      in different ways for boys and girls. Other risk factors differed by sex. For
      instance, alcohol use and sex initiation predicted multiple forms of TDV
      perpetration for boys, whereas weapon carrying and emotional symptoms predicted
      several forms of TDV perpetration for girls. CONCLUSIONS: The prevalence of TDV
      was high in our sample. Important sex differences in rates of perpetration and
      risk factors emerged. Comprehensive prevention programs that target TDV and
      related risk factors, such as bullying and other risk factors, seem warranted.

PMID- 25620455
TI  - Peste des Petits Ruminants Viruses Re-emerging in China, 2013-2014.
AB  - Re-emergence of peste des petits ruminants (PPR) was officially reported in
      Xinjiang Uygur Autonomous Region in north-western China in November 2013, and
      then along with the movements of goats and sheep, this disease rapidly spread to
      other provinces, autonomous regions and municipalities (P/A/M) of China. A total
      of 256 PPR-affected counties in 22 P/A/M were identified up to September 2014.
      Phylogenetic analysis revealed that the current circulating strains and Tibet
      strains isolated previously in 2007, both belonged to lineage IV but in different
      sub-branches. Nevertheless, compared with the Tibet strains, the current
      circulating strains shared high degree of genetic homology with those from
      Pakistan and Tajikistan. 

PMID- 25620456
TI  - Cutaneous squamous cell carcinoma in Norway 1963-2011: increasing incidence and
      stable mortality.
AB  - The incidence of cutaneous squamous cell carcinoma (SCC) is rapidly increasing in
      white populations, causing high morbidity and health-care costs. Few studies,
      however, have described the trends for SCC, as population-based data with a long
      follow-up are limited. In Norway we have this opportunity and we aimed to
      describe SCC incidence, mortality and survival rates, according to sex, age,
      stage, primary anatomical location, and geographical region, for the period 1963
      2011, for estimation of future health-care needs. Data were retrieved from the
      Cancer Registry of Norway. Age-adjusted SCC incidence and mortality rates and 5
      year relative survival (in percent) were calculated for 5-year calendar periods.
      A joinpoint regression model identified the annual percentage change (APC) in
      rates over the 50-year period. The age-adjusted incidence rate increased ninefold
      in females and sixfold in males from 1963 to 2011, with APCs of 5.6% (95%
      confidence interval, CI 4.5, 7.3) and 3.3% (95% CI 1.3, 5.3) in females and
      males, respectively. SCC incidence rose in all age groups, anatomical locations
      (except ears in females), and geographical regions, though restricted to
      localized tumors. Most striking increase was seen in the age group 70-79, in face
      and head locations and among residents in southern Norway. SCC mortality and
      survival rates remained relatively stable. Our findings underline an increasing
      need for SCC treatment in Norway, especially considering the aging population.
      The findings also call for the creation of particular guidelines for primary
      prevention of SCC. 

PMID- 25620457
TI  - Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone
      diagnostic cut-off values by tandem mass spectrometry.
AB  - OBJECTIVES: To validate the diagnostic utility of Cortrosyn(TM) stimulated
      aldosterone in the differentiation of primary (PAI) and secondary adrenal
      insufficiency (SAI) and to evaluate the effect of urine sodium levels and posture
      on test performance. DESIGN: Cross-sectional study. METHODS: Healthy volunteers
      (HV; n = 46) and patients with PAI (n = 26) and SAI (n = 29) participated in the
      study. Testing included cortisol and aldosterone (by liquid-chromatography tandem
      mass spectrometry) measurements at baseline and 30 and 60 min after 250 MUg
      Cortrosyn(TM). Plasma corticotropin (ACTH), renin activity (PRA) and urine spot
      sodium as a proxy for 24-h urine sodium excretion were measured at baseline. The
      effect of a sitting or semifowlers posture was evaluated in healthy volunteers.
      RESULTS: A Cortrosyn(TM)-stimulated aldosterone level of 5 ng/dl (0.14 nmol/l)
      had 88% sensitivity and positive predictive value and 89.7% specificity and
      negative predictive value for distinguishing PAI from SAI. Spot urine sodium
      levels showed a strong correlation with peak aldosterone levels (r = -0.55, P =
      0.02, n = 18) in the SAI but not PAI or HV groups. Posture did not have a
      significant effect on results. CONCLUSIONS: Once diagnosed with adrenal
      insufficiency, a stimulated aldosterone value of 5 ng/dl (0.14 nmol/l) works well
      to differentiate PAI from SAI. However, clinicians should be aware of the
      possible effect of total body sodium as reflected by spot urine sodium levels on
      aldosterone results. A 24-h urine sodium measurement may be helpful in
      interpretation.

PMID- 25620459
TI  - Erratum to: Effect of Antibiotic Down-Regulatory Gene wblA Ortholog on Antifungal
      Polyene Production in Rare Actinomycetes Pseudonocardia autotrophica.
AB  - This erratum is being published to correct the third author's name. The third
      author, Young-Woo Kim should read as Ying-Yu Jin. Young-Woo Kim is a Korean
      Chinese. The original legal name of Young-Woo Kim is Ying-Yu Jin. The corrected
      version of this article is available in the Archive (http://jmb.or.kr). 

PMID- 25620458
TI  - Meta-narrative analysis of sports injury reporting practices based on the Injury
      Definitions Concept Framework (IDCF): A review of consensus statements and
      epidemiological studies in athletics (track and field).
AB  - OBJECTIVES: Consistency in routines for reporting injury has been a focus of
      development efforts in sports epidemiology for a long time. To gain an improved
      understanding of current reporting practices, we applied the Injury Definitions
      Concept Framework (IDCF) in a review of injury reporting in a subset of the
      field. DESIGN: Meta-narrative review. METHODS: An analysis of injury definitions
      reported in consensus statements for different sports and studies of injury
      epidemiology in athletics (track and field) published in PubMed between 1980 and
      2013 was performed. Separate narratives for each of the three reporting contexts
      in the IDCF were constructed from the data. RESULTS: Six consensus statements and
      14 studies reporting on athletics injury epidemiology fulfilled the selection
      criteria. The narratives on sports performance, clinical examination, and athlete
      self-report contexts were evenly represented in the eligible studies. The sports
      performance and athlete self-report narratives covered both professional and
      community athletes as well as training and competition settings. In the clinical
      examination narrative, data collection by health service professionals was linked
      to studies of professional athletes at international championships. CONCLUSIONS:
      From an application of the IDCF in a review of injury reporting in sports
      epidemiology we observed a parallel usage of reporting contexts in this field of
      research. The co-existence of reporting methodologies does not necessarily
      reflect a problematic situation, but only provided that firm precautions are
      taken when comparing studies performed in the different contexts.

PMID- 25620460
TI  - Site-dependence of van der Waals interaction explains exciton spectra of double
      walled tubular J-aggregates.
AB  - The simulation of the optical properties of supramolecular aggregates requires
      the development of methods, which are able to treat a large number of coupled
      chromophores interacting with the environment. Since it is currently not possible
      to treat large systems by quantum chemistry, the Frenkel exciton model is a
      valuable alternative. In this work we show how the Frenkel exciton model can be
      extended in order to explain the excitonic spectra of a specific double-walled
      tubular dye aggregate explicitly taking into account dispersive energy shifts of
      ground and excited states due to van der Waals interaction with all surrounding
      molecules. The experimentally observed splitting is well explained by the site
      dependent energy shift of molecules placed at the inner or outer side of the
      double-walled tube, respectively. Therefore we can conclude that inclusion of the
      site-dependent dispersive effect in the theoretical description of optical
      properties of nanoscaled dye aggregates is mandatory. 

PMID- 25620461
TI  - LC-MS/MS quantitative determination of Tetrapterys mucronata alkaloids, a plant
      occasionally used in ayahuasca preparation.
AB  - INTRODUCTION: Tetrapterys mucronata Cav. (Malpighiaceae) is a plant used in some
      regions of Brazil in the preparation of ayahuasca. OBJECTIVE: To determine the
      content of the main tryptamine alkaloids in the stem bark of T. mucronata Cav.
      and assess their possible toxic and hallucinogenic properties based on the doses
      found in a water decoction that mimics the ayahuasca preparation. METHODS: Four
      alkaloids previously described for their toxic and hallucinogenic properties were
      quantitated by multiple reaction monitoring HPLC combined with electrospray
      ionisation and tandem MS (HPLC-ESI/MS/MS) in the water decoction and ethanolic
      extracts from the bark of T. mucronata. RESULTS: Exhaustive extraction of the
      stem barks with ethanol revealed the following alkaloid levels: bufotenine (1)
      3.26 +/- 0.31 mg/g, 5-methoxy-N-methyltryptamine (2) 0.88 +/- 0.08 mg/g, 5
      methoxy-bufotenine (3) 3.07 +/- 0.22 mg/g and 2-methyl-6-methoxy-1,2,3,4
      tetrahydro-beta-carboline (4) 0.14 +/- 0.004 mg/g. The water decoction presented
      slightly lower levels, ranging between 2.32 +/- 0.14, 0.50 +/- 0.04, 1.53 +/-
      0.09 and 0.10 +/- 0.01 mg/g for (1), (2), (3) and (4) respectively. CONCLUSIONS:
      The HPLC-ESI/MS/MS quantitation revealed significant alkaloid levels, in
      particular for bufotenine and 5-methoxy-bufotenine. As such compounds are known
      for their toxic and hallucinogenic properties, these results indicate that the
      consumption of this plant as an ingredient in ayahuasca preparations may present
      a risk to consumers.

PMID- 25620462
TI  - Effects of dynamic hyperinflation on exercise capacity and quality of life in
      stable COPD patients.
AB  - BACKGROUND AND AIMS: Dynamic hyperinflation (DH) is an important
      pathophysiological characteristic of chronic obstructive pulmonary disease
      (COPD). There is increasing evidence that DH has negative effects on exercise
      performance and quality of life. The objective of this study was to explore
      effects of DH on exercise capacity and quality of life in stable COPD patients.
      METHODS: Fifty-eight COPD patients and 20 matched healthy individuals underwent
      pulmonary function test, 6-min walk test and symptom-limited cardiopulmonary
      exercise test (CPET). End-expiratory lung volume/total lung capacity ratio
      (EELVmax/TLC) at peak exercise of CPET was evaluated, and EELVmax/TLC >= 75% was
      defined as 'severe dynamic hyperinflation (SDH)'. RESULTS: Of the 58 patients
      studied, 29 (50.0%) presented with SDH (SDH+ group, EELVmax/TLC 79.60 +/- 3.60%),
      having worse maximal exercise capacity reflected by lower peakload, maximal
      oxygen uptake (VO2 max), maximal carbon dioxide output (VCO2 max) and maximal
      minute ventilation (VEmax) than did those without SDH (SDH- group, EELVmax/TLC
      67.44 +/- 6.53%). The EELVmax/TLC ratio at peak exercise had no association with
      variables of pulmonary function and 6-min walk distance (6MWD), but correlated
      inversely with peakload, VO2 max, VCO2 max and VEmax (r = -0.300~-0.351, P <
      0.05). Although no significant differences were observed, patients with
      EELVmax/TLC >= 75% tended to have higher COPD assessment test score (15.07 +/-
      6.55 vs 13.28 +/- 6.59, P = 0.303). CONCLUSIONS: DH develops variably during
      exercise and has a greater impact on maximal exercise capacity than 6MWD, even in
      those with the same extent of pulmonary function impairment at rest.

PMID- 25620463
TI  - In honor of Professor Larry Kricka as he retires from Luminescence.

PMID- 25620466
TI  - A novel one-class SVM based negative data sampling method for reconstructing
      proteome-wide HTLV-human protein interaction networks.
AB  - Protein-protein interaction (PPI) prediction is generally treated as a problem of
      binary classification wherein negative data sampling is still an open problem to
      be addressed. The commonly used random sampling is prone to yield less
      representative negative data with considerable false negatives. Meanwhile
      rational constraints are seldom exerted on model selection to reduce the risk of
      false positive predictions for most of the existing computational methods. In
      this work, we propose a novel negative data sampling method based on one-class
      SVM (support vector machine, SVM) to predict proteome-wide protein interactions
      between HTLV retrovirus and Homo sapiens, wherein one-class SVM is used to choose
      reliable and representative negative data, and two-class SVM is used to yield
      proteome-wide outcomes as predictive feedback for rational model selection.
      Computational results suggest that one-class SVM is more suited to be used as
      negative data sampling method than two-class PPI predictor, and the predictive
      feedback constrained model selection helps to yield a rational predictive model
      that reduces the risk of false positive predictions. Some predictions have been
      validated by the recent literature. Lastly, gene ontology based clustering of the
      predicted PPI networks is conducted to provide valuable cues for the pathogenesis
      of HTLV retrovirus. 

PMID- 25620468
TI  - Inverse metabolic engineering of Bacillus subtilis for xylose utilization based
      on adaptive evolution and whole-genome sequencing.
AB  - Efficient utilization of xylose by bacteria is essential for production of fuels
      and chemicals from lignocellulosic biomass. In this study, Bacillus subtilis 168
      was subjected to laboratory adaptive evolution, and a mutant E72, which could
      grow on xylose with a maximum specific growth rate of 0.445 h(-1), was obtained.
      By whole-genome sequencing, 16 mutations were identified in strain E72. Through
      further analysis, three of them, which were in the coding regions of genes araR,
      sinR, and comP, were identified as the beneficial mutations. The reconstructed
      strain 168ARSRCP harboring these three mutations exhibited similar growth
      capacity on xylose to the evolved strain E72, and the average xylose consumption
      rate of this strain is 0.530 g/l/h, much higher than that of E72 (0.392 g/l/h).
      Furthermore, genes acoA and bdhA were deleted and the final strain could utilize
      xylose to produce acetoin at 71 % of the maximum theoretical yield. These results
      suggested that this strain could be used as a potential platform for production
      of fuels and chemicals from lignocellulosic biomass.

PMID- 25620467
TI  - Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude
      mice.
AB  - BACKGROUND: Combination of androgen ablation along with early detection and
      surgery has made prostate cancer highly treatable at the initial stage. However,
      this cancer remains the second leading cause of cancer death among American men
      due to castration-resistant progression, suggesting that novel therapeutic agents
      are urgently needed for this life-threatening condition. Phosphatidylinositol 3
      kinase p110beta is a major cellular signaling molecule and has been identified as
      a critical factor in prostate cancer progression. In a recent report, we
      established a nanomicelle-based strategy to deliver p110beta-specific inhibitor
      TGX221 to prostate cancer cells by conjugating the surface of nanomicelles with a
      RNA aptamer against prostate specific membrane antigen (PSMA) present in all
      clinical prostate cancers. In this study, we tested this nanomicellar TGX221 for
      its in vivo anti-tumor effect in mouse xenograft models. METHODS: Prostate cancer
      cell lines LAPC-4, LNCaP, C4-2 and 22RV1 were used to establish subcutaneous
      xenograft tumors in nude mice. Paraffin sections from xenograft tumor specimens
      were used in immunohistochemistry assays to detect AKT phosphorylation, cell
      proliferation marker Ki67 and proliferating cell nuclear antigen (PCNA), as well
      as 5-bromo-2-deoxyuridine (BrdU) incorporation. Quantitative PCR assay was
      conducted to determine prostate-specific antigen (PSA) gene expression in
      xenograft tumors. RESULTS: Although systemic delivery of unconjugated TGX221
      significantly reduced xenograft tumor growth in nude mice compared to solvent
      control, the nanomicellar TGX221 conjugates completely blocked tumor growth of
      xenografts derived from multiple prostate cancer cell lines. Further analyses
      revealed that AKT phosphorylation and cell proliferation indexes were
      dramatically reduced in xenograft tumors received nanomicellar TGX221 compared to
      xenograft tumors received unconjugated TGX221 treatment. There was no noticeable
      side effect by gross observation or at microscopic level of organ tissue section.
      CONCLUSION: These data strongly suggest that prostate cancer cell-targeted
      nanomicellar TGX221 is an effective anti-cancer agent for prostate cancer.

PMID- 25620469
TI  - Prenatal findings of holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a rare brain abnormality characterized by an
      incomplete cleavage of the primitive prosencephalon of forebrain during early
      embryogenesis. To determine the clinical characteristics and outcome of fetuses
      with HPE, we retrospectively analyzed nine patients who were prenatally diagnosed
      as fetal HPE by ultrasounds. The mean diagnostic weeks were 20 weeks of
      gestation. Two cases died within one day after birth. The chromosomal
      examinations were performed in seven cases (trisomy 18: n = 2; trisomy 13: n = 2;
      45,XX,der(18)t(18;21)(p10;p10)mat: n = 1; normal karyotype: n = 2). In our HPE
      cases, most cases had serious facial anomalies and poor prognosis. Our data
      suggested that the early prenatal diagnosis of HPE allowed time for parental
      counseling and delivery planning.

PMID- 25620470
TI  - Effect of cigarette smoking on insulin resistance risk.
AB  - OBJECTIVES: Smoking is one of the main risk factors for cardiovascular disease
      (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly
      understood; however, a number of atherogenic characteristics, such as insulin
      resistance have been reported. We aim to investigate the effects of cigarette
      smoking on insulin resistance and to determine the correlation between this
      parameter with smoking status characteristics. STUDY DESIGN: This study was
      conducted on 138 non-smokers and 162 smokers aged respectively 35.6+/-16.0 and
      38.5+/-21.9 years. All subjects are not diabetic. METHODS: Fasting glucose was
      determined by enzymatic methods and insulin by chemiluminescence method. Insulin
      resistance (IR) was estimated using the Homeostasis Model of Assessment equation:
      HOMA-IR=[fasting insulin (mU/L)*fasting glucose (mmol/L)]/22.5. IR was defined as
      the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and
      reflect insulin resistance. RESULTS: Compared to non-smokers, smokers had
      significantly higher levels of fasting glucose, fasting insulin and HOMA-IR
      index. These associations remained significant after adjustment for confounding
      factors (age, gender, BMI and alcohol consumption). A statistically significant
      association was noted between the smoking status parameters, including both the
      number of cigarettes smoked/day and the duration of smoking, and fasting insulin
      levels as well for HOMA-IR index. Among smokers, we noted a positive correlation
      between HOMA-IR index and both plasma thiocyanates and urinary cotinine.
      CONCLUSION: Our results show that smokers have a high risk to developing an
      insulin resistance and hyperinsulinemia, compared with a matched group of non
      smokers, and may help to explain the high risk of cardiovascular diseases in
      smokers.

PMID- 25620471
TI  - Uncertainty of prebiotic scenarios: the case of the non-enzymatic reverse
      tricarboxylic acid cycle.
AB  - We consider the hypothesis of the primordial nature of the non-enzymatic reverse
      tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the
      uncertainty of this hypothesis due to the combinatorial aspect of the constituent
      chemical transformations. Our results suggest that a) rTCA cycle belongs to a
      degenerate optimum of auto-catalytic cycles, and b) the set of targets for
      investigations of the origin of the common metabolic core should be significantly
      extended. 

PMID- 25620472
TI  - Synthesis and characterization of Her2-NLP peptide conjugates targeting
      circulating breast cancer cells: cellular uptake and localization by fluorescent
      microscopic imaging.
AB  - To synthesize a fluorescent Her2-NLP peptide conjugate consisting of Her2/neu
      targeting peptide and nuclear localization sequence peptide (NLP) and assess its
      cellular uptake and intracellular localization for radionuclide cancer therapy
      targeting Her2/neu-positive circulating breast cancer cells (CBCC). Fluorescent
      Cy5.5 Her2-NLP peptide conjugate was synthesized by coupling a bivalent peptide
      sequence, which consisted of a Her2-binding peptide (NH2-GSGKCCYSL) and an NLP
      peptide (CGYGPKKKRKVGG) linked by a polyethylene glycol (PEG) chain with 6
      repeating units, with an activated Cy5.5 ester. The conjugate was separated and
      purified by HPLC and then characterized by Maldi-MS. The intracellular
      localization of fluorescent Cy5.5 Her2-NLP peptide conjugate was assessed by
      fluorescent microscopic imaging using a confocal microscope after incubation of
      Cy5.5-Her2-NLP with Her2/neu positive breast cancer cells and Her2/neu negative
      control breast cancer cells, respectively. Fluorescent signals were detected in
      cytoplasm of Her2/neu positive breast cancer cells (SKBR-3 and BT474 cell lines),
      but not or little in cytoplasm of Her2/neu negative breast cancer cells (MDA-MB
      231), after incubation of the breast cancer cells with Cy5.5-Her2-NLP conjugates
      in vitro. No fluorescent signals were detected within the nuclei of Her2/neu
      positive SKBR-3 and BT474 breast cancer cells, neither Her2/neu negative MDA-MB
      231 cells, incubated with the Cy5.5-Her2-NLP peptide conjugates, suggesting poor
      nuclear localization of the Cy5.5-Her2-NLP conjugates localized within the
      cytoplasm after their cellular uptake and internalization by the Her2/neu
      positive breast cancer cells. Her2-binding peptide (KCCYSL) is a promising agent
      for radionuclide therapy of Her2/neu positive breast cancer using a beta(-) or
      alpha emitting radionuclide, but poor nuclear localization of the Her2-NLP
      peptide conjugates may limit its use for eradication of Her2/neu-positive CBCC
      using I-125 or other Auger electron emitting radionuclide. 

PMID- 25620474
TI  - [Research on gastric cancer stem cells: current status, problems and future
      directions].

PMID- 25620473
TI  - Generalized multilevel function-on-scalar regression and principal component
      analysis.
AB  - This manuscript considers regression models for generalized, multilevel
      functional responses: functions are generalized in that they follow an
      exponential family distribution and multilevel in that they are clustered within
      groups or subjects. This data structure is increasingly common across scientific
      domains and is exemplified by our motivating example, in which binary curves
      indicating physical activity or inactivity are observed for nearly 600 subjects
      over 5 days. We use a generalized linear model to incorporate scalar covariates
      into the mean structure, and decompose subject-specific and subject-day-specific
      deviations using multilevel functional principal components analysis. Thus,
      functional fixed effects are estimated while accounting for within-function and
      within-subject correlations, and major directions of variability within and
      between subjects are identified. Fixed effect coefficient functions and principal
      component basis functions are estimated using penalized splines; model parameters
      are estimated in a Bayesian framework using Stan, a programming language that
      implements a Hamiltonian Monte Carlo sampler. Simulations designed to mimic the
      application have good estimation and inferential properties with reasonable
      computation times for moderate datasets, in both cross-sectional and multilevel
      scenarios; code is publicly available. In the application we identify effects of
      age and BMI on the time-specific change in probability of being active over a 24
      hour period; in addition, the principal components analysis identifies the
      patterns of activity that distinguish subjects and days within subjects. 

PMID- 25620475
TI  - [Suppression of ATR reverses the cisplatin resistance in ovarian cancer SKOV3
      cells].
AB  - OBJECTIVE: To explore the effect of ataxia telangiectasia mutated and RAD3
      related protein (ATR) expression and ATR kinase activity on the sensitivity to
      cisplatin in ovarian cancer SKOV3 cells. METHODS: SiRNA targeting ATR was
      transfected into SKOV3 cells for 48 h to reduce the ATR protein level, and ATR
      kinase inhibitor VE-821 was used for 12 h to inhibit the ATR pathway activity.
      The alteration of cell viability was examined by CCk-8 assay. Expression levels
      of ATR, p-ATR and gamma-H2AX proteins were detected by Western blot. The DNA
      double strand breaks (DSB) marker gamma-H2AX and homologous recombination repair
      key protein RAD51 and their co-localization in the cells were examined under the
      confocal microscope. The status of DNA double strand breaks (DSB) in single cells
      was visualized by alkaline comet assay. Finally, the cell cycle distribution was
      assessed using flow cytometry. RESULTS: DDP caused evident DNA double strands
      breaks and activated ATR kinase pathway. ATR-siRNA notably reduced ATR protein
      level, the 48 h IC(50) value of DDP was 72.12 umol/L and 41.25 umol/L,
      respectively, in the NC-siRNA and ATR-siRNA groups (P < 0.05). Confocal
      microscopic assay presented decreased recruitment of RAD51 at the DSB loci and
      comet assay showed enhanced DSB in the cells after ATR knocking down. After the
      inhibition of ATR kinase by VE-821, the 48 h IC(50) value of DDP was 75.32 umol/L
      and 45.64 umol/L, respectively, in the DMSO and VE-821 groups (P < 0.05 for
      both), confocal microscopic assay demonstrated reduced RAD51 recruitment, and
      comet assay showed increased DSB in cells after ATR kinase inhibition. Flow
      cytometry showed that percentage of cells distributed in G(0)/G(1), S and G(2)/M
      phases was 71.2%, 13.4% and 15.4%, repectively, after 40 umol/L DDP treatment for
      24 h. Compared with that of control group (G(0)/G(1): 54.2%, S: 21.3% and G(2)/M:
      24.4%), DDP induced G(0)/G(1) phase arrest. DDP intervention resulted in the cell
      cycle status (G(0)/G(1): 43.2%, S: 20.4%, G(2)/M: 36.4%) in the ATR-siRNA group
      and (G(0)/G(1): 40.2%, S: 22.5%, G(2)/M: 37.3%) in the VE-821 group, indicating
      that the inhibition of ATR or ATR kinase could abrogate the effect of G(0)/G(1)
      phase arrest induced by DDP. CONCLUSIONS: Suppression of ATR can affect the
      homologous recombination repair in ovarian cancer cells, leading to accumulation
      of DNA double strand breaks in the cell nuclei as well as reduction of DDP-caused
      G(0)/G(1) phase arrest, finally enhances the sensitivity to cisplatin in the
      ovarian cancer SKOV3 cells.

PMID- 25620476
TI  - [Estradiol enhances the proliferation and migration of Ishikawa cells by
      promotion of angiogenesis induced by activation of NF-kappaB via AKT pathway].
AB  - OBJECTIVE: The aim of this study was to explore whether estradiol induces the
      expression of VEGF and bFGF in the endometrial cancer Ishikawa cells by
      activation of NF-kappaB via AKT pathway, and its effect on cell proliferation.
      METHODS: Western blot was used to detect the AKT protein expression in Ishikawa
      cells after stimulation with estradiol, and the effect of AKT inhibitor or ER
      inhibitor on the activation of AKT. TransAM kit was used to detect the NF-kappaB
      p65 activity. qPCR and Western blot were used to detect the expression of VEGF
      and bFGF mRNA and proteins in the Ishikawa cells after estradiol treatment (E2
      group), and pretreated with AKT inhibitor (AKT group) or ER inhibitor (ER group)
      or NF-kappaB inhibitor (NF-kappaB group), following the estradiol treatment. Flow
      cytometry and CFSE (carboxyfluorescein diacetate, succinimidyl ester) staining
      were used to examine the cell proliferation. Transwell was used to detect the
      migration ability of Ishikawa cells. RESULTS: Expression of p-AKT protein in the
      Ishikawa cells was markedly higher than that in the control group (P < 0.05).
      Expressions of p-AKT protein in the AKT and ER groups were significantly
      decreased than that in the E2 group (P < 0.05). The NF-kappaB activity was
      highest after stimulation with 1*10(-6) mol/L estradiol for 30 min to 1 h. AKT
      inhibitor significantly reduced the NF-kappaB activity (P < 0.05). The
      expressions of VEGF and bFGF mRNA and proteins in the E2 group were significantly
      increased than that in the control group (P < 0.05), and their expression in the
      AKT, ER and NF-kappaB groups were significantly decreased than that in the E2
      group (P < 0.05). The proliferation and migration abilities of the Ishikawa cells
      were significantly increased after estradiol stimulation. CONCLUSIONS: Estradiol
      induces the production of VEGF and bFGF through activating NF-kappaB via AKT
      pathway, and enhances the proliferation and migration ability of cancer cells.

PMID- 25620477
TI  - [Biological function and molecular mechanism of URI in HepG2 cells].
AB  - OBJECTIVE: To explore the effect and molecular mechanism of the unconventional
      prefoldin RPB5 interactor (URI) in hepatocellular carcinoma HepG2 cells. METHODS:
      The cDNA sequence and shRNA of URI were obtained and sub-cloned into eukaryotic
      expression vectors. Then those vectors were transfected into HepG2 cells to
      obtain stable transfection cell line. The cell proliferation and anchor
      independent growth in URI-overexpressing and knockdown HepG2 cells were
      determined by CCK-8 and soft agar colony assay. Flow cytometry was applied to
      detect the cell cycle and apoptosis of gamma-ray irradiated cells. Apoptosis
      related genes were detected by Western blot. RESULTS: The pCDNA3.1-URI and pGPU6
      URIi eukaryotic expression vectors were constructed successfully and
      corresponding stable transfection cell lines were obtained. Cell proliferation
      rates of the HepG2, pCDNA3.1-URI-HepG2 and pGPU6-URIi-HepG2 cells were (588.78 +/
      32.12)%, (959.33 +/- 58.8)% and (393.93 +/- 39.7)%, respectively (P < 0.05). The
      number of cell clones of HepG2, pCDNA3.1-URI-HepG2 and pGPU6-URIi-HepG2 cells
      were 43 +/- 7, 85 +/- 5 and 20 +/- 4 (P < 0.05), respectively. After gamma-ray
      irradiation, the URI-overexpressing cell line showed a significantly lower
      apoptosis rate and G(2)/M phase arrest than those in the URI-depleted cell line
      (P < 0.05). In the HepG2 cells, the relative protein expression levels of URI,
      Bax and Bcl-2 were 0.92 +/- 0.03, 1.11 +/- 0.13 and 0.82 +/- 0.01 (P < 0.05). In
      the pCDNA3.1-URI-HepG2 cells, the relative protein expression levels of URI, Bax
      and Bcl-2 were 1.79 +/- 0.12, 0.48 +/- 0.01 and 2.20 +/- 0.30 (P < 0.05),
      respectively. In the pGPU6-URIi-HepG2 cells, the relative protein expression
      levels of URI, Bax and Bcl-2 were 0.50 +/- 0.04, 1.52 +/- 0.20 and 0.38 +/- 0.01
      (P < 0.05), respectively. The expression of Bax was down-regulated and Bcl-2 was
      up-regulated in the URI-overexpressing cell line. However, on the contrary,
      expression of Bax was up-regulated and Bcl-2 was down-regulated in the URI
      depleted cell line. CONCLUSIONS: URI may promote the growth of hepatocellular
      carcinoma cells via inhibition of cell proliferation and reducing the apoptosis
      in hepatocellular carcinoma cells in vitro. After the impairment of URI
      expression, the proliferation ability of hepatocellular carcinoma cells is
      suppressed and the ability to resist gamma-ray irradiation is reduced. URI may
      become a potential new target for cancer therapy of hepatocellular carcinoma.

PMID- 25620478
TI  - [Expression of CC-chemokine ligand 18 (CCL18) in the serum and pleural effusion
      of non-small-cell lung cancer patients and its regulatory effect on the
      differentiation of monocyte-derived dendritic cells].
AB  - OBJECTIVE: To compare the CC-chemokine ligand 18 (CCL18) expression in the serum
      and malignant pleural effusion (MPE) of NSCLC patients and explore its regulatory
      effect on differentiation of monocyte-derived dendritic cells (Mo-DC). METHODS:
      CCL18 levels in the serum and MPE from 62 NSCLC patients were quantitated by
      immunoassay. CCL18 in sera from 26 healthy individuals, 28 exudative pleural
      effusions from inflammatory pulmonary diseases and 17 transudative pleural
      effusions from non-inflammatory diseases were used as control. Mo-DC was
      generated by culturing NSCLC-derived monocytes with GM-CSF and IL-4 in the
      presence or absence of CCL18. The mean fluorescent intensity (MFI) of CD14, CD80,
      CD83, CD86 and HLA-DR were analyzed by flow cytometry (FCM). Mo-DC was then co
      cultured with purified T cells and the percence of CD25(+)FoxP3(+) cells was
      assayed by FCM. RESULTS: CCL18 levels in the sera of NSCLC patients and healthy
      individuals were (132.70 +/- 15.52) ng/ml and (18.44 +/- 0.99) ng/ml,
      respectively (P < 0.001). The levels of CCL18 in MPE, exudative PE and
      transudative PE were (155.6 +/- 13.58) ng/ml, (190.4 +/- 22.33) ng/ml and (20.89
      +/- 3.03) ng/ml, respectively. CCL18 in the MPE was significantly higher than
      that in transudates (P < 0.001), however, no significant difference was observed
      between CCL18 expression in exudative PE and MPE (P = 0.172). Of note, a moderate
      positive correlation (r = 0.421, P < 0.01) was observed between CCL18 levels in
      the paired MPE and serum of NSCLC. In the healthy control group, Mo-DC cultured
      in the presence of CCL18 showed 31.4 +/- 15.8 (MFI) of CD14 expression, which was
      significantly higher than that in Mo-DC cultured in the absence of CCL18 (18.5 +/
      8.9, P < 0.05). In contrast, the expressions of MFI of CD80, CD83, CD86 and HLA
      DR were significantly decreased upon CCL18 induction (P < 0.05). In the NSCLC
      group, GM-CSF+IL-4+CCL18 induced a MFI of 45.2 +/- 13.8 of CD14 expression in Mo
      DC, which was also significantly higher than that of GM-CSF+ IL-4 induction (22.6
      +/- 10.5, P < 0.01). Similarly, the expressions of MFI of CD80, CD83, CD86 and
      HLA-DR were significantly decreased in the presence of CCL18 (P < 0.05).
      Furthermore, the MFI of CD14, CD83, CD86 and HLA-DR had significant differences
      between GM-CSF/IL-4/CCL18-induced Mo-DC derived from NSCLC patients and healthy
      control (P < 0.05). Finally, CD4(+) T cells co-cultured with NSCLC-derived, GM
      CSF/IL-4/CCL18-treated Mo-DC had significantly higher percent of CD25(+)FoxP3(+)
      cells compared with that of CD4(+) T cells stimulated with Mo-DC induced by GM
      CSF/IL-4(P < 0.01). CONCLUSIONS: CCL18 is present at a high level in MPE and
      serum of NSCLC patients complicated with pleural effusion and a moderate positive
      correlation exists between CCL18 levels in the two fluids. CCL18 inhibits
      maturation of Mo-DC, which consequently stimulates T cells to differentiate into
      CD25(+)FoxP3(+) regulatory T cells.

PMID- 25620479
TI  - [Expression and clinical significance of CCL5 in patients with esophageal
      carcinoma].
AB  - OBJECTIVE: To investigate the expression and significance of CCL5 in patients
      with esophageal carcinoma. METHODS: Using reverse transcriptase polymerase chain
      reaction (RT-PCR), the expressions of CCL5/CD8/granzyme B/perforin in tumor and
      corresponding adjacent tissues from esophageal carcinoma patients were examined.
      Flow cytometry (FACS) was used to detect the percentages of CD8(+) T cells and
      CCR5(+)CD8(+) T cells in TIL and PBMC from the patients. Transwell assay was
      performed to study the effect of CCL5 on the migration of T cells in vitro. T
      test and Spearman correlation analysis were performed. RESULTS: The mRNA
      expressions of CCL5 and perforin were 0.348 2 +/- 0.300 1 and 0.181 9 +/- 0.118
      6, respectively, in the tumor samples, while their expressions in adjacent
      samples were 0.279 6 +/- 0.138 0 and 0.118 0 +/- 0.109 8, respectively, with no
      statistically significant differences between them (P > 0.05 for both). The mRNA
      expressions of CD8 and granzyme B were significantly higher in the tumor tissues
      than in adjacent tissues (0.464 9 +/- 0.300 8 vs. 0.279 0 +/- 0.173 4, 0.648 7 +/
      0.516 0 vs. 0.469 7 +/- 0.259 1; P < 0.05 for both). The relative expression of
      CCL5 was positively correlated with that of CD8, perforin and granzyme B (r(CD8)
      = 0.272, P = 0.034; r(perforin) = 0.305, P = 0.026; r(granzymeB) = 0.108, P =
      0.012) in the tumor sites. FACS data revealed that the proportions of CD8(+) T
      cells in TIL and PBMC were (45.86 +/- 16.09)% and (34.05 +/- 15.07)%,
      respectively, showing a significant difference (P = 0.022). Similarly,
      CCR5(+)CD8(+) T cells fraction in TIL (48.12 +/- 26.75)% was much higher than
      that in PBMC (19.53 +/- 13.67) % (P < 0.001). Transwell assay showed that CCL5
      protein enhanced the migration of T cells, supporting that CCL5 is crucial for
      CD8(+) T cells recruitment in vivo. Intriguingly, CCL5 expression was down
      regulated in advanced patients (stage IIb-IV). The accumulation of CD8(+) T cells
      and CCR5(+)CD8(+) T cells was strongly reduced in advanced patients, suggesting
      that CCL5 expression may be involved in the local control of the disease and its
      reduction may be involved in disease progression. CONCLUSIONS: The current data
      indicate the involvement of CCL5 in the regulation of CD8(+) T cell entry into
      tumor lesions in esophageal carcinoma patients. This process may affect the
      disease status and potentially as a prognostic factor for cancer patients.
      Enhancing local CCL5 expression in tumor lesions may represent a novel strategy
      in esophageal cancer therapy.

PMID- 25620480
TI  - [Changes of fibroblast immunophenotype and their clinical significance in stromal
      remodeling of breast tumors].
AB  - OBJECTIVE: To evaluate the immunophenotype conversion of fibroblasts and its
      clinical significance in the process of breast tumor stromal remodeling. METHODS:
      CD34, FAP-alpha, p63 and a-SMA were detected by immunohistochemistry in 273
      breast biopsies, including 60 normal breast tissues, 46 atypical ductal
      hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive
      carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC). RESULTS: The positive
      expression rates of CD34, FAP-alpha and alpha-SMA in the stromal fibroblasts of
      normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the
      stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively.
      Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%,
      respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively.
      The expressions of CD34, alpha-SMA and FAP-alpha in the stromal fibroblasts of
      normal, ASH and DCIS breast tissues did not show significant differences (chi(2)
      = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor
      host interface at the invasive front of ADH and DCIS lesions was CD34(+)alpha
      SMA(+)FAP-alpha(+). There were statistically significant differences in the
      expression of CD34, alpha-SMA and FAP-alpha between IDC and ADH, DCIS and normal
      breast tissues (chi(2) = 8.351, P < 0.001). The immunophenotype of stromal
      fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) alpha-SMA(+) FAP
      alpha(+). CONCLUSIONS: Immunophenotype conversion from CD34(+) alpha-SMA(-) FAP
      alpha(-) to CD34(-) alpha-SMA(+)FAP-alpha(+) may be a sensitive indicator to
      judge whether DCIS has microinvasion. Detection of the immunophenotype conversion
      of stromal fibroblasts may be helpful to determine the presence of microinvasion,
      and to improve the diagnostic accuracy rate of DCIS.

PMID- 25620481
TI  - [Expression of leptin and adiponectin in esophageal squamous cell carcinoma and
      their clinical significance].
AB  - OBJECTIVE: To preliminarily investigate the expression and clinical significance
      of leptin and adiponectin in esophageal squamous cell carcinoma (ESCC). METHODS:
      The expression of leptin and adiponectin in ESCC and normal esophageal mucosal
      tissue was detected by immunohistochemical staining with tissue microarray. The
      correlation between leptin, adiponectin and clinicalpathological features was
      statistically analyzed. RESULTS: The expression of leptin was significantly
      upregulated in the ESCC than in the normal esophageal mucosa tissue [65.6%
      (80/122) versus 27.5% (11/40), P < 0.001]. Expression of leptin was significantly
      correlated with lymph node involvement and advanced tumor stage (P = 0.009 and P
      = 0.043, respectively). Expression of adiponectin was significantly down
      regulated in ESCC compared with that in normal esophageal mucosal tissue [22.1%
      (27/122) versus 47.5% (19/40), P = 0.002]. Expression of adiponectin was
      significantly correlated with lymph node involvement (P = 0.020). Correlation
      analysis showed a positive correlation between the expression of leptin and lymph
      node metastasis and TNM stage (r = 0.235 and r = 0.183, respectively), and a
      negative correlation between the expression of adiponectin and lymph node
      metastasis (r = -0.229). There was no significant correlation between the
      expressions of leptin and adiponectin (P > 0.05), and between the body mass index
      and the expression of leptin and adiponectin, and lymph node metastasis (P > 0.05
      for all). CONCLUSIONS: An imbalanced expression of adipocytokines exits in ESCC.
      The expression of leptin and adiponectin is correlated with lymph node metastasis
      and/or tumor stage. Therefore, imbalanced expression of leptin and adiponectin
      may have a potential role in the carcinogenesis and disease progression of ESCC.

PMID- 25620482
TI  - [Correlations between DNA mismatch repair (MMR) and prognosis and prediction of
      treatment efficacy in stage II/II colon cancer].
AB  - OBJECTIVE: To investigate the role of DNA mismatch repair (MMR) as a prognostic
      indicator of radical resection and a predictor of fluorouracil-based adjuvant
      therapy benefit in patients with stage II/III colon cancer. METHODS: The
      clinicopathological characteristics of 172 patients with stage II/III colon
      cancer who underwent radical resection were retrospectively analyzed.
      Immunohistochemical staining was used to detect the expression of DNA mismatch
      repair (MLH1/MSH2/MSH6/PMS2) in the tumor tissues. RESULTS: Among a total of 172
      patients, there were 38 (22.1%) cases with defective DNA mismatch repair (dMMR)
      and 134 (77.9%) cases with proficient DNA mismatch repair (pMMR). Among the 115
      patients who did not receive adjuvant chemotherapy, those with tumor displaying
      dMMR had a better 5-year overall survival (OS) rate and disease-free survival
      (DFS) rate than the patients with proficient DNA mismatch repair (pMMR) (88.0%
      vs. 66.7%, P = 0.040; 84.0% vs. 60.0%, P = 0.034). The benefit of adjuvant
      chemotherapy differed significantly according to the MMR status. Adjuvant 5-Fu
      chemotherapy improved the 5-year overall survival rate among 134 patients with
      pMMR (86.4%) than that in patients treated by surgery alone (66.7%, P = 0.012).
      By contrast, there was no benefit of adjuvant 5-Fu chemotherapy in the patients
      with dMMR (61.5% vs. 86.4%, P = 0.062), which was even more clear the 5-year
      disease-free survival rate (53.8% vs. 84.0%, P = 0.038). CONCLUSIONS: MMR status
      is a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage
      II/III colon cancer. Patients with stage II/III colon cancer displaying dMMR have
      a better prognosis than those with pMMR.

PMID- 25620483
TI  - [Prevalence and viral load of human papillomavirus in squamous cell carcinomas of
      the head and neck in different nationalities in Xingjiang area].

PMID- 25620484
TI  - [Current trends of breast reconstruction after mastectomy for breast cancer
      patients in China: a survey report].
AB  - OBJECTIVE: To explore the current trends of breast reconstruction (BR) for breast
      cancer patients in China. METHODS: A questionnaire was designed for this study,
      and it included questions on surgeon demographics, number of mastectomy and BR,
      type and timing of BR, reconstructive choices in the setting of preoperative or
      postoperative radiotherapy or chemotherapy, etc. All data were collected until
      December 2012. Questionnaires were sent to 52 members of the Committee of Breast
      Cancer Society by e-mail or mail. RESULTS: By July 2013, 41 questionnaires had
      been returned. Among all, 5 were excluded for not performing BR. These 36
      hospitals covered 22 provinces and municipalities in China. A total of 538
      surgeons working in the general surgery or oncological surgery department, but
      only 123 (22.9%) were qualified to perform BR. In 2012, except for 4 missing
      data, 24, 763 mastectomies were performed in 32 hospitals; among them, 1120
      (4.5%) received BR. According to these 36 respondents, 32 (88.9%) performed
      prosthetic (1, 843 cases in all) while 4 (11.1%) performed prosthetic BR with
      acellular dermal matrix (17 cases in all) from the time of their first BR
      operation to the end of 2012. During the same period, 965 latissimus dorsi
      myocutaneous flaps with implant were performed in 23 (63.9%) hospitals while 738
      latissimus dorsi myocutaneous flaps without implant were performed in 32 (88.9%)
      hospitals. At the same time, 366 pedicled transverse rectus abdominis
      myocutaneous flap BRs were performed in 28 (77.8%) hospitals, while 155 abdominal
      free flap BRs were carried out in 9 (25.0%) hospitals. The overall complication
      rate was 18.2%. Postoperative radiotherapy had some effect on influencing the
      esthetic outcomes of BR, so the autologous BR was recommended, but the timing
      remained controversial. Regarding chemotherapy, most respondents concluded that
      it had no effect or only a mild effect. The overall cosmetic outcomes of the
      reconstructed breasts satisfied the majority of physicians and patients.
      CONCLUSIONS: With more attention paid to the quality of life after mastectomy,
      more and more BRs are needed, but the ratio is still low in China. To improve
      this situation, more efforts are needed, including the improvement of the
      intrahospital framework of multi-disciplinary service, the training for doctors
      and the educational program for patients, etc.

PMID- 25620485
TI  - [Clinicopathological features and prognostic analysis of 151 patients with
      primary extra-nodal non-Hodgkin's lymphoma].
AB  - OBJECTIVE: To evaluate the epidermiology, clinicopathological features and
      prognosis of primary extra-nodal non-Hodgkin's lymphoma (PE-NHL). METHODS: The
      clinicopathological data of 151 patients diagnosed as PE-NHL in the First
      Affiliated Hospital of Jilin University between January 2007 and December 2011
      were reviewed and analyzed. RESULTS: The proportion of PE-NHL patients was 58.8%
      among all the non-Hodgkin's lymphoma cases, with the average age of 52 years, and
      the male/female ratio was 1.16:1. The most frequently involved site was the
      stomach (30.5%) followed by nose and sinuses (19.9%) and Waldeyer's ring (17.2%).
      The most common subtype was diffuse large B-cell lymphoma (DLBCL) (55.0%),
      followed by NK/T (18.5%) and extra-nodal marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT) ( 13.2%). The distribution of clinical stages
      was as follows: stage I 20.5%, II 29.8%, III 29.1%, and IV 20.5%. Most nasal PE
      NHL is in early stages, with a proportion of 76.7% in stages I & II. The 3-year
      overall survival rate was 73.2% and 3-year progression free survival rate was
      46.6% in the PE-DLBCL patients. The International Prognosis Index (IPI) could be
      used to estimate the prognosis of PE-DLBCL well. Multivariate analysis showed
      that ESR and curative effect of the first treatment were independent prognostic
      factors for PE-DLBCL patients. CONCLUSIONS: The incidence of PE-NHL is quite
      high, and the most common primary extra-nodal site is the gastro-intestinal tract
      and the most common subtype is diffuse large B-cell lymphoma. Risk groups based
      on IPI can indicate the prognosis of PE-DLBCL to some extent, but only the ESR
      and curative effect of the first treatment are confirmed to be independent risk
      factors.

PMID- 25620486
TI  - [Comparison of perioperative outcomes and lymphadenectomy after thoracoscopic
      esophagectomy in semi prone position and open esophagectomy].
AB  - OBJECTIVE: Thoracoscopic esophagectomy has gained worldwide popularity. This
      study compared the perioperative outcomes and lymphadenectomy after thoracoscopic
      esophagectomy in semi prone position and open esophagectomy. METHODS: Sixty-two
      consecutive patients after thoracoscopic esophagectomy were compared with 62
      patients who underwent open esophagectomy. Outcomes included surgical time, blood
      loss, length of hospital stay, 30-day mortality, complications and gained lymph
      nodes. RESULTS: The mean length of hospital stay of the thoracoscopic group was
      12.4 +/- 7.4 days, and 13.6 +/- 6.7 days in the open esophagectomy group (P >
      0.05). The median total operation time and median thoracic operation time were
      270 and 130 min, the median total blood loss and median thoracic blood loss were
      300 and 180 ml in the thoracoscopic group, while the results in open
      esophagectomy group were 290, 150 min and 300, 180 ml. The median total operation
      time and median thoracic operation time were of statistically significant
      difference (P < 0.01). But there were no significant differences between the two
      groups in total blood loss and thoracic blood loss (P > 0.05) . The numbers of
      obtained lymph nodes in the thoracoscopic group and open esophagectomy group were
      20.5 and 16.9 (P < 0.01). Among them, the median numbers of mediastinal lymph
      nodes in the thoracoscopic group and open esophagectomy group were 12.4 and 8.8,
      the left recurrent laryngeal nerve lymph nodes were 1.8 and 1.0, and the right
      recurrent laryngeal nerve lymph nodes were 2.9 and 1.2 (P < 0.01 for all). There
      were 8 positive recurrent laryngeal nerve lymph nodes (12.9%) in the
      thoracoscopic group, while 5 in the open esophagectomy group (8.1%, P > 0.05).
      There were no peri-operative period death, heavy bleeding, or thoracic gastric
      fistula in both groups. CONCLUSIONS: Thoracoscopic esophagectomy in semi prone
      position may achieve good surgical field exposure, therefore, to make
      esophagectomy, lymph node dissection and digestive tract reconstruction possible.
      These findings suggest that with further technical refinement, thoracoscopic
      esophagectomy may have the upper hand on reducing postoperative complications and
      performing mediastinal lymph node dissection.

PMID- 25620487
TI  - [Clinical analysis of 53 cases of retroperitoneal schwannoma].
AB  - OBJECTIVE: To explore the clinical characteristics, diagnosis and treatment
      regimens for retroperitoneal schwannoma. METHODS: Clinicopathological data of 53
      retroperitoneal schwannoma patients treated from January 1999 to April 2013 in
      our hospital were collected and analyzed using SPSS 13.0 statistical software.
      RESULTS: Symptoms of the retroperitoneal schwannoma were vague and nonspecific.
      12 patients had interrupted abdominal pain, 9 patients had abdominal discomfort,
      and only 6 patients presented with abdominal mass while 24 patients were detected
      by health checkup. There were some characteristics but not specific findings in
      imaging examination such as CT, ultrasonography and MRI, so preoperative
      diagnosis rate was low with only 9 patients diagnosed as retroperitoneal
      schwannoma and 21 patients diagnosed as neurogenic tumor. S-100
      immunohistochemisty was very important in pathological diagnosis, and the
      patients with benign retroperitoneal schwannoma got 100% tumor specific 5-year
      survival after complete excision while the 5-year survival of malignant
      retroperitoneal schwannoma was only 50.0%. CONCLUSIONS: Retroperitoneal
      schwannoma is a rare disease. Most of them are benign tumors, and complete
      surgical excision is the effective treatment.

PMID- 25620488
TI  - [Associations between physical exercise and quality of life in breast cancer
      patients].
AB  - OBJECTIVE: To investigate the associations between physical exercise and quality
      of life in breast cancer patients. METHODS: A cross-sectional study was conducted
      among 3 344 community breast cancer patients between April and July 2013 in
      Shanghai, China. Data were collected using a questionnaire, including socio
      demographic situation, cancer survival and health behaviors, and scores of EORTC
      QLQ-C30 Simplified Chinese version and FACT-G Simplified Chinese version.
      RESULTS: Among a total of 3 344 breast cancer patients, the patients doing
      exercise reported significantly higher EORTC physical functioning scores, role
      functioning scores, emotional functioning scores, global health scores, and FACT
      G physical well-being scores, social well-being scores, emotional well-being
      scores, functional well-being scores, and FACT-G total scores than the patients
      who didn't take exercise (P < 0.05, P(Adjusted)<0.05) . Breast cancer patients
      who did exercise more than or equal to 5 times/week reported significantly higher
      EORTC role functioning scores, cognitive functioning scores, emotional
      functioning scores, global health scores and FACT-G physical well-being scores,
      functional well-being scores, and FACT-G total scores than patients who did
      exercise less than 5 times/week (P < 0.05, P(Adjusted)<0.05 ). CONCLUSIONS: There
      are active associations between physical exercise and quality of life in breast
      cancer patients. Engagement in physical exercise is beneficial to breast cancer
      patients with long-term survival.

PMID- 25620489
TI  - [Expert consensus on diagnosis and treatment of chemotherapy-induced
      thrombocytopenia in cancer patients (2014 version].

PMID- 25620491
TI  - Do we need to revise the tripartite subdivision hypothesis of the human
      subthalamic nucleus (STN)? Response to Alkemade and Forstmann.
AB  - Recently in this journal, Alkemade and Forstmann again challenged the evidence
      for a tripartite organisation to the subthalamic nucleus (STN) (Alkemade &
      Forstmann 2014). Additionally, they raised specific issues with the earlier
      published results using 3T MRI to perform in vivo diffusion weighted imaging
      (DWI) based segmentation of the STN (Lambert et al. 2012). Their comments reveal
      a common misconception related to the underlying methodologies used, which we
      clarify in this reply, in addition to highlighting how their current conclusions
      are synonymous with our original paper. The ongoing debate, instigated by the
      controversies surrounding STN parcellation, raises important implications for the
      assumptions and methodologies employed in mapping functional brain anatomy, both
      in vivo and ex vivo, and reveals a fundamental emergent problem with the current
      techniques. These issues are reviewed, and potential strategies that could be
      developed to manage them in the future are discussed further. 

PMID- 25620490
TI  - Hexavalent chromium induces expression of mesenchymal and stem cell markers in
      renal epithelial cells.
AB  - Cr(VI) causes severe kidney damage. The patient's renal function could gradually
      recover by spontaneous kidney regeneration. The molecular effect of Cr(VI) on
      recovery of kidney cells, however, has not been clearly elucidated. Here we show
      that Cr(VI) induces expression of mesenchymal and stem cell markers, cell
      markers, such as paxillin, vimentin, alpha-SMA, nanog, and CD133 of HK-2 cells.
      Moreover, Cr(VI) activates epithelial-to-mesenchymal transition (EMT). By
      revealing that levels of dihydrodiol dehydrogenase were promptly reduced
      following Cr(VI) challenge, our data suggested that DDH could be involved in a
      Cr(VI)-related oxidation to generate massive reactive oxygen species and H2 O2 ,
      and to create intracellular hypoxia, which then increased levels of SUMO-1
      activating enzyme subunit 2, and sumoylation of eukaryotic elongation factor-2,
      to mediate the subsequent molecular and cellular responses, e.g., expression of
      mesenchymal and stem cell markers. Pretreatment with vitamin C reduced Cr(VI)
      related cellular effects. However, no evident effect was observed when vitamin C
      was added following Cr(VI) challenge.

PMID- 25620492
TI  - Multiple brain networks underpinning word learning from fluent speech revealed by
      independent component analysis.
AB  - Although neuroimaging studies using standard subtraction-based analysis from
      functional magnetic resonance imaging (fMRI) have suggested that frontal and
      temporal regions are involved in word learning from fluent speech, the possible
      contribution of different brain networks during this type of learning is still
      largely unknown. Indeed, univariate fMRI analyses cannot identify the full extent
      of distributed networks that are engaged by a complex task such as word learning.
      Here we used Independent Component Analysis (ICA) to characterize the different
      brain networks subserving word learning from an artificial language speech
      stream. Results were replicated in a second cohort of participants with a
      different linguistic background. Four spatially independent networks were
      associated with the task in both cohorts: (i) a dorsal Auditory-Premotor network;
      (ii) a dorsal Sensory-Motor network; (iii) a dorsal Fronto-Parietal network; and
      (iv) a ventral Fronto-Temporal network. The level of engagement of these networks
      varied through the learning period with only the dorsal Auditory-Premotor network
      being engaged across all blocks. In addition, the connectivity strength of this
      network in the second block of the learning phase correlated with the individual
      variability in word learning performance. These findings suggest that: (i) word
      learning relies on segregated connectivity patterns involving dorsal and ventral
      networks; and (ii) specifically, the dorsal auditory-premotor network
      connectivity strength is directly correlated with word learning performance. 

PMID- 25620494
TI  - The complete mitochondrial genome of Micrura ignea Schwartz & Norenburg 2005
      (Nemertea: Heteronemertea) and comparative analysis with other nemertean
      mitogenomes.
AB  - We sequenced the complete mitochondrial genome of the Heteronemertea species,
      Micrura ignea. The genome was amplified with a combination of short and long PCRs
      that were subjected to 454 sequencing. The mitogenome of M. ignea is a circular
      molecule of 15,333bp in size and encodes the 37 genes typically found in
      metazoans, and one non-coding region. The order of the genes is the same as for
      all the other Heteronemerteans. All genes are encoded on the heavy strand except
      trnT and trnP. The phylogenetic analyses recovered M. ignea as a basal taxon in
      the Lineidae family, no differences were found in the topology of the
      phylogenetic trees in comparison with previous studies. 

PMID- 25620493
TI  - Impaired consciousness is linked to changes in effective connectivity of the
      posterior cingulate cortex within the default mode network.
AB  - The intrinsic connectivity of the default mode network has been associated with
      the level of consciousness in patients with severe brain injury. Especially
      medial parietal regions are considered to be highly involved in impaired
      consciousness. To better understand what aspect of this intrinsic architecture is
      linked to consciousness, we applied spectral dynamic causal modeling to assess
      effective connectivity within the default mode network in patients with disorders
      of consciousness. We included 12 controls, 12 patients in minimally conscious
      state and 13 in vegetative state in this study. For each subject, we first
      defined the four key regions of the default mode network employing a subject
      specific independent component analysis approach. The resulting regions were then
      included as nodes in a spectral dynamic causal modeling analysis in order to
      assess how the causal interactions across these regions as well as the
      characteristics of neuronal fluctuations change with the level of consciousness.
      The resulting pattern of interaction in controls identified the posterior
      cingulate cortex as the main driven hub with positive afferent but negative
      efferent connections. In patients, this pattern appears to be disrupted.
      Moreover, the vegetative state patients exhibit significantly reduced self
      inhibition and increased oscillations in the posterior cingulate cortex compared
      to minimally conscious state and controls. Finally, the degree of self-inhibition
      and strength of oscillation in this region is correlated with the level of
      consciousness. These findings indicate that the equilibrium between excitatory
      connectivity towards posterior cingulate cortex and its feedback projections is a
      key aspect of the relationship between alterations in consciousness after severe
      brain injury and the intrinsic functional architecture of the default mode
      network. This impairment might be principally due to the disruption of the
      mechanisms underlying self-inhibition and neuronal oscillations in the posterior
      cingulate cortex. 

PMID- 25620495
TI  - LC-MS-based metabolomics identification of novel biomarkers of chorioamnionitis
      and its associated perinatal neurological damage.
AB  - Chorioamnionitis is a complication of pregnancy associated with significant
      maternal and perinatal long-term adverse outcomes. We apply high-throughput
      amniotic fluid (AF) metabolomics analysis for better understanding the
      pathophysiological mechanism of chorioamnionitis and its associated perinatal
      neurological injury and to provide meaningful information about new potential
      biomarkers. AF samples (n = 40) were collected from women at risk of
      chorioamnionits. Detailed clinical information on each pregnancy was obtained
      from obstetrical and neonatal medical examination. Liquid chromatography
      (LC)/mass spectrometry (MS) followed by data alignment and filtration as well as
      univariate and multivariate statistical analysis was performed. Statistically
      significant differences were found in 60 masses in positive and 115 in negative
      ionization mode obtained with LC/quadrupole time-of-flight MS (LC-QTOF-MS)
      between women with and without chorioamnionitis. Identified compounds were mainly
      related to glycerophospholipids and sphingolipids metabolism. From them,
      LPE(16:0)/LPE(P-16:0) and especially lactosylceramides emerged as the best
      biomarker candidates. Sulfocholic acid, trioxocholenoic acids, and LPC(18:2) were
      particularly increased in women with chorioamnionitis whose newborns developed
      perinatal brain damage. Therefore, we propose LPE(16:0)/LPE(P-16:0) and
      lactosylceramides as biomarkers for chorioamnionitis as well as LPC(18:2),
      trioxocholenoic acid, and sulfocholic acid for its associated perinatal brain
      damage. Metabolomics fingerprinting of AF enables the prediction of pregnancy
      related disorders and the development of new diagnostics strategies. 

PMID- 25620496
TI  - Dalbergia odorifera Extract Ameliorates UVB-Induced Wrinkle Formation by
      Modulating Expression of Extracellular Matrix Proteins.
AB  - Preclinical Research Emerging evidence suggests that Dalbergia odorifera T. Chen
      (Leguminosae), an indigenous medicinal herb, has therapeutic potential. This
      study examined the antiwrinkle effects of ethanol extracts of D. odorifera in UVB
      irradiated human skin cells. Ethanol extracts of D. odorifera and thier
      constituents, dalbergin and sativanone, induced expression of collagen type I and
      transforming growth factor (TGF)-beta1 in human dermal fibroblasts. In HR-1
      hairless mice exposed to UVB, the ethanol extract reduced wrinkle formation and
      skin thickness. This inhibitory effect of ethanol extract was associated with the
      restoration of collagen type I, TGF-beta1, and elastin to levels approaching
      those in skin tissues not exposed to UVB, which was accompanied by the reduction
      of matrix metalloproteinase-2 and upregulation of tissue inhibitors of
      metalloproteinase (TIMP)-2 and TIMP-3 in skin tissue exposed to UVB. These
      results suggest that the ethanol extracts prevent some effects of photoaging and
      maintain skin integrity by regulating the degradation of the extracellular matrix
      proteins. (c) 2015 Wiley Periodicals, Inc.

PMID- 25620499
TI  - Effect of sample dilution on matrix effects in pesticide analysis of several
      matrices by liquid chromatography-high-resolution mass spectrometry.
AB  - This study used two LC columns of different adsorbents and liquid chromatography
      electrospray ionization-high-resolution mass spectrometry to study the
      relationship between matrix effects (ME), the LC separations, and elution
      patterns of pesticides and those of matrix components. Using calibration
      standards of 381 pesticides at three dilution levels of 1*, 1/10*, and 1/100*,
      108 samples were prepared in solvent and five different sample matrices for the
      study. Results obtained from principal component analysis and slope ratios of
      calibration curves provided measurements of the ME and showed the 1/100* sample
      dilution could minimize suppression ME for most pesticides analyzed. Should a
      pesticide coeluting with matrix components have a peak intensity of 25 times or
      higher, the suppression for that pesticide would persist even at 1/100* dilution.
      The number of pesticides had enhancement ME increased with increasing dilution
      from 1* to 1/100*, with those early eluting, hydrophilic pesticides affected the
      most. 

PMID- 25620498
TI  - Histopathology in the placentae of women with antiphospholipid antibodies: A
      systematic review of the literature.
AB  - BACKGROUND: Antiphospholipid antibodies (aPLs) are a heterogenous group of
      autoantibodies associated with recurrent miscarriage, stillbirth, foetal growth
      restriction and premature birth. The cause of obstetric morbidity in women with
      aPLs is not completely understood. Workers have attempted to understand the role
      of aPLs in obstetric morbidity by investigating the histopathology of placentae
      from aPL-positive women. However, it is unclear from these diverse, and at times
      contradictory reports what histopathological lesions are common in the placentae
      of women with aPLs. This systematic review was undertaken to generate a complete
      picture of the placental features associated with aPLs in an attempt to
      understand the pathological processes that occur in pregnancies affected by aPLs.
      METHODS: Pubmed, Scopus, Web of Science and Embase were searched on the 27th
      November 2014 using the keywords "placenta" OR "trophoblast" AND
      "antiphospholipid antibody" OR "antiphospholipid antibody syndrome". Records that
      were relevant and eligible were qualitatively assessed and given a score out of
      24. RESULTS: Of the 1112 records that were retrieved from the systematic search,
      34 records were eligible for review, and were qualitatively scored. Of the 44
      histopathological features that were reported in 580 placentae from aPL-positive
      women, six features appeared to be more common in the placentae of aPL-positive
      women compared to control women, including: placental infarction, impaired spiral
      artery remodelling, decidual inflammation, increased syncytial knots, decreased
      vasculosyncytial membranes and the deposition of complement split product C4d.
      CONCLUSION: Based on the evidence in this systematic review, a human placental
      aPL fingerprint has been proposed. The diversity of the human placental aPL
      fingerprint suggests that multiple pathological processes may occur in
      pregnancies affected by aPL.

PMID- 25620500
TI  - Synthetic devices for reconstructive surgery of the cruciate ligaments: a
      systematic review.
AB  - PURPOSE: The role of synthetic devices in the management of the cruciate ligament
      injured knee remains controversial. The aim of this systematic review was to
      assess the safety and efficacy of synthetic devices in cruciate ligament surgery.
      METHODS: A systematic review of the electronic databases Medline, Embase, and The
      Cochrane Library (issue 1, 2014) on January 13, 2014, was performed to identify
      controlled and uncontrolled trials. Trials that assessed the safety and efficacy
      of synthetic devices for cruciate ligament surgery were included. The main
      variables assessed included rates of failure, revision, and noninfective effusion
      and synovitis. Patient-reported outcome assessments and complications were also
      assessed where reported. RESULTS: From 511 records screened, we included 85
      articles published between 1985 and 2013 reporting on 6 synthetic devices
      (ligament augmentation and reconstruction system [Ligament Augmentation and
      Reconstruction System (LARS; Surgical Implants and Devices, Arc-sur-Tille,
      France)]; Leeds-Keio [Xiros (formerly Neoligaments), Leeds, England]; Kennedy
      ligament augmentation device [3M, St Paul, MN]; Dacron [Stryker, Kalamazoo, MI];
      Gore-Tex [W.L. Gore and Associates, Flagstaff, AZ]; and Trevira [Telos (limited
      liability company), Marburg, Germany]). The heterogeneity of the included studies
      precluded meta-analysis. The results were analyzed by device and then type of
      reconstruction (anterior cruciate ligament [ACL]/posterior cruciate ligament
      [PCL]/combined ACL and PCL). The lowest cumulative rates of failure were seen
      with the LARS device (2.6% for ACL and 1% for PCL surgery). The highest failure
      rate was seen in the Dacron ACL group (cumulative rate, 33.6%). Rates of
      noninfective synovitis and effusion ranged from 0.2% in the LARS ACL group to
      27.6% in the Gore-Tex ACL group. Revision rates ranged from 2.6% (LARS) to 11.8%
      (Trevira-Hochfest; Telos). Recent designs, specifically the LARS, showed good
      improvement in the outcome scores. The mean preoperative and postoperative
      Lysholm knee scores were 54 and 88, respectively; the mean preoperative and
      postoperative Tegner activity scale scores were 3.3 and 6, respectively.
      CONCLUSIONS: Preliminary results for newer-generation devices, specifically the
      LARS, show lower reported rates of failure, revision, and sterile
      effusion/synovitis when compared with older devices. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level II through IV studies.

PMID- 25620497
TI  - IgE recognition patterns in peanut allergy are age dependent: perspectives of the
      EuroPrevall study.
AB  - BACKGROUND: We tested the hypothesis that specific molecular sensitization
      patterns correlate with the clinical data/manifestation in a European peanut
      allergic population characterized under a common protocol. METHODS: Sixty-eight
      peanut-allergic subjects and 82 tolerant controls from 11 European countries were
      included. Allergy to peanut and lowest symptom-eliciting dose was established by
      double-blind placebo-controlled food challenge in all but anaphylactic subjects.
      Information of early or late (before or after 14 years of age) onset of peanut
      allergy was obtained from standardized questionnaires. IgE to peanut allergens
      rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. RESULTS:
      Seventy-eight percent of peanut allergics were sensitized to peanut extract and
      90% to at least one peanut component. rAra h 2 was the sole major allergen for
      the peanut-allergic population. Geographical differences were observed for rAra h
      8 and rAra h 9, which were major allergens for central/western and southern
      Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed
      in early-onset peanut allergy. Peanut-tolerant subjects were frequently
      sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2
      >= 1.0 kUA /l conferred a 97% probability for a systemic reaction (P = 0.0002).
      Logistic regression revealed a significant influence of peanut extract
      sensitization and region on the occurrence of systemic reactions (P = 0.0185 and
      P = 0.0436, respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is
      usually acquired in childhood. IgE to Ara h 2 >= 1.0 kUA /l is significantly
      associated with the development of systemic reactions to peanut.

PMID- 25620507
TI  - Training the next generation of pediatric nephrology advocates: the John E. Lewy
      Foundation Advocacy Scholars Program.

PMID- 25620508
TI  - Nutritional and metabolic assessment for children receiving long-term ventilation
      at home: a call to action for clinicians?

PMID- 25620509
TI  - 50 years ago in the Journal of Pediatrics: the teratogenicity of maternal
      rubella.

PMID- 25620510
TI  - 50 years ago in the Journal of Pediatrics: light-induced seizures.

PMID- 25620511
TI  - 50 years ago in the Journal of Pediatrics: enteric disease due to
      enteropathogenic Escherichia coli in hospitalized infants in Kotzebue, Alaska.

PMID- 25620512
TI  - Computational gene expression modeling identifies salivary biomarker analysis
      that predict oral feeding readiness in the newborn.
AB  - OBJECTIVE: To combine mathematical modeling of salivary gene expression
      microarray data and systems biology annotation with reverse-transcription
      quantitative polymerase chain reaction amplification to identify (phase I) and
      validate (phase II) salivary biomarker analysis for the prediction of oral
      feeding readiness in preterm infants. STUDY DESIGN: Comparative whole
      transcriptome microarray analysis from 12 preterm newborns pre- and postoral
      feeding success was used for computational modeling and systems biology analysis
      to identify potential salivary transcripts associated with oral feeding success
      (phase I). Selected gene expression biomarkers (15 from computational modeling; 6
      evidence-based; and 3 reference) were evaluated by reverse-transcription
      quantitative polymerase chain reaction amplification on 400 salivary samples from
      successful (n = 200) and unsuccessful (n = 200) oral feeders (phase II). Genes,
      alone and in combination, were evaluated by a multivariate analysis controlling
      for sex and postconceptional age (PCA) to determine the probability that newborns
      achieved successful oral feeding. RESULTS: Advancing PCA (P < .001) and female
      sex (P = .05) positively predicted an infant's ability to feed orally. A
      combination of 5 genes, neuropeptide Y2 receptor (hunger signaling), adneosine
      monophosphate-activated protein kinase (energy homeostasis), plexin A1 (olfactory
      neurogenesis), nephronophthisis 4 (visual behavior), and wingless-type MMTV
      integration site family, member 3 (facial development), in addition to PCA and
      sex, demonstrated good accuracy for determining feeding success (area under the
      receiver operator characteristic curve = 0.78). CONCLUSIONS: We have identified
      objective and biologically relevant salivary biomarkers that noninvasively assess
      a newborn's developing brain, sensory, and facial development as they relate to
      oral feeding success. Understanding the mechanisms that underlie the development
      of oral feeding readiness through translational and computational methods may
      improve clinical decision making while decreasing morbidities and health care
      costs.

PMID- 25620513
TI  - 50 years ago in the Journal of Pediatrics: a study of blood glucose and ketone
      bodies and plasma free fatty acids, cholesterol, phospholipids, and total lipids
      in juvenile diabetes.

PMID- 25620514
TI  - 50 years ago in the Journal of Pediatrics: surface properties and lipids from
      lungs of infants with hyaline membrane disease.

PMID- 25620515
TI  - 50 years ago in the Journal of Pediatrics: trypsinogen deficiency disease.

PMID- 25620516
TI  - Hemiscrotal hematoma in the newborn-don't forget adrenal hemorrhage.

PMID- 25620517
TI  - Cellulitic lesion on the thigh.

PMID- 25620519
TI  - The dilemma of International Pediatric Congresses in Europe: starting the debate.

PMID- 25620518
TI  - Reply: To PMID 24411521.

PMID- 25620520
TI  - A highly accurate symmetric optical flow based high-dimensional nonlinear spatial
      normalization of brain images.
AB  - Spatial normalization plays a key role in voxel-based analyses of brain images.
      We propose a highly accurate algorithm for high-dimensional spatial normalization
      of brain images based on the technique of symmetric optical flow. We first
      construct a three dimension optical model with the consistency assumption of
      intensity and consistency of the gradient of intensity under a constraint of
      discontinuity-preserving spatio-temporal smoothness. Then, an efficient inverse
      consistency optical flow is proposed with aims of higher registration accuracy,
      where the flow is naturally symmetric. By employing a hierarchical strategy
      ranging from coarse to fine scales of resolution and a method of Euler-Lagrange
      numerical analysis, our algorithm is capable of registering brain images data.
      Experiments using both simulated and real datasets demonstrated that the accuracy
      of our algorithm is not only better than that of those traditional optical flow
      algorithms, but also comparable to other registration methods used extensively in
      the medical imaging community. Moreover, our registration algorithm is fully
      automated, requiring a very limited number of parameters and no manual
      intervention. 

PMID- 25620521
TI  - Accelerating patch-based directional wavelets with multicore parallel computing
      in compressed sensing MRI.
AB  - Compressed sensing MRI (CS-MRI) is a promising technology to accelerate magnetic
      resonance imaging. Both improving the image quality and reducing the computation
      time are important for this technology. Recently, a patch-based directional
      wavelet (PBDW) has been applied in CS-MRI to improve edge reconstruction.
      However, this method is time consuming since it involves extensive computations,
      including geometric direction estimation and numerous iterations of wavelet
      transform. To accelerate computations of PBDW, we propose a general
      parallelization of patch-based processing by taking the advantage of multicore
      processors. Additionally, two pertinent optimizations, excluding smooth patches
      and pre-arranged insertion sort, that make use of sparsity in MR images are also
      proposed. Simulation results demonstrate that the acceleration factor with the
      parallel architecture of PBDW approaches the number of central processing unit
      cores, and that pertinent optimizations are also effective to make further
      accelerations. The proposed approaches allow compressed sensing MRI
      reconstruction to be accomplished within several seconds. 

PMID- 25620522
TI  - Evaluation of MRI issues at 3-Tesla for a transcatheter aortic valve replacement
      (TAVR) bioprosthesis.
AB  - OBJECTIVE: Replacement of the aortic heart valve typically requires open-heart
      surgery. A new transcatheter aortic valve replacement (TAVR) bioprosthesis made
      from metallic material was recently developed that is an advantageous alternative
      insofar as it is implanted using a minimally invasive procedure. Because of the
      presence of metal, there are safety issues related to MRI. Therefore, the purpose
      of this study was to use standardized testing techniques to evaluate MRI issues
      for this TAVR bioprosthesis in association with a 3-Tesla MR system. METHODS: The
      TAVR bioprosthesis (Hydra Aortic Valve, Percutaneous Heart Valve Prosthesis,
      Vascular Innovations Company, Ltd, Thailand) was evaluated for magnetic field
      interactions (translational attraction and torque), MRI-related heating at a
      relative high specific absorption rate level (whole body average SAR, 2.9-W/kg),
      and artifacts (T1-weighted, spin echo, and gradient echo pulse sequences) at 3
      Tesla. RESULTS: The TAVR bioprosthesis demonstrated negligible magnetic field
      interactions (deflection angle, 3-degrees; torque, 0) and minimal heating
      (maximum temperature rise, 2.5 degrees C; background temperature rise, 1.7
      degrees C). Artifacts were relatively small in relation to the size and shape of
      the implant. CONCLUSIONS: The TAVR bioprosthesis that was evaluated in this
      investigation is acceptable, or using current MRI terminology "MR Conditional",
      for a patient undergoing MRI at 3-Tesla or less.

PMID- 25620523
TI  - In silico peptide prediction for antibody generation to recognize 5
      enolpyruvylshikimate-3-phosphate synthase (EPSPS) in genetically modified
      organisms.
AB  - For the prospective immunorecognition of 5-enolpyruvylshikimate-3-phosphate
      synthase (CP4-EPSPS) as a biomarker protein expressed by transgenic soybean, an
      extensive in silico evaluation of the referred protein was performed. The main
      objective of this study was the selection of a set of peptides that could
      function as potential immunogens for the production of novel antibodies against
      CP4-EPSPS protein. For this purpose, the protein was in silico cleaved with
      trypsin/chymotrypsin and the resultant peptides were extensively analyzed for
      further selection of the best candidates for antibody production. The analysis
      enabled the successful proposal of four peptides with potential immunogenicity
      for their future use as screening biomarkers of genetically modified organisms.
      To our knowledge, this is the first attempt to select and define potential linear
      epitopes for the immunization of animals and, subsequently, to generate adequate
      antibodies for CP4-EPSPS recognition. The present work will be followed by the
      synthesis of the candidate peptides to be incubated in animals for antibody
      generation and potential applicability for the development of an immunosensor for
      CP4-EPSPS detection.

PMID- 25620524
TI  - Tonsillar metastasis of small cell lung carcinoma.
AB  - Metastasis to palatine tonsils are rare, accounting from only 0.8% of all
      tonsillar tumors, so far only 100 cases reported in the English literature. Only
      a few cases have been reported for small cell and non-small cell lung cancer as a
      primary site. With a diagnosis of small cell lung cancer, a 68-year-old male
      patient relapsed after six cycles of chemotherapy in tonsilla palatina and
      cervical lymph nodes. Patients died 26 months after being diagnosed with lung
      cancer and 2 months after detection of tonsil metastasis. We present the current
      case report because of the rarity of metastasis to tonsil in lung cancer.

PMID- 25620525
TI  - A unique open reading frame within the comX gene of Streptococcus mutans
      regulates genetic competence and oxidative stress tolerance.
AB  - Streptococcus mutans displays complex regulation of genetic competence, with ComX
      controlling late competence gene transcription. The rcrRPQ operon has been shown
      to link oxidative stress tolerance, (p)ppGpp metabolism and competence in S.
      mutans. Importantly, an rcrR polar (DeltarcrR-P) mutant is hyper-transformable,
      but an rcrR non-polar (DeltarcrR-NP) mutant cannot be transformed. Transcriptome
      comparisons of the rcrR mutants using RNA-Seq and quantitative real-time
      polymerase chain reaction revealed little expression in the 5' region of comX in
      DeltarcrR-NP, but high level expression in the 3' region. Northern blotting with
      comX probes revealed two distinct transcripts in the DeltarcrR-P and DeltarcrR-NP
      strains, and 5' Rapid Amplification of cDNA Ends mapped the 5' terminus of the
      shorter transcript to nt +140 of the comX structural gene, where a unique 69-aa
      open reading frame, termed XrpA, was encoded in a different reading frame than
      ComX. Two single-nucleotide substitution mutants (comX::T162C; comX::T210A) were
      introduced to disrupt XrpA without affecting the sequence of ComX. When the
      mutations were in the DeltarcrR-NP genetic background, ComX production and
      transformation were restored. Overexpression of xrpA led to impaired growth in
      aerobic conditions and decreased transformability. These results reveal an
      unprecedented mechanism for competence regulation and stress tolerance by a gene
      product encoded within the comX gene that appears unique to S. mutans. 

PMID- 25620527
TI  - Clinical esophagology: alive and kicking!

PMID- 25620526
TI  - Hippocampal contribution to implicit configuration memory expressed via eye
      movements during scene exploration.
AB  - Although hippocampus unequivocally supports explicit/declarative memory, fewer
      findings have demonstrated its role in implicit expressions of memory. We tested
      for hippocampal contributions to an implicit expression of configural/relational
      memory for complex scenes using eye-movement tracking during functional magnetic
      resonance imaging (fMRI) scanning. Participants studied scenes and were later
      tested using scenes that resembled study scenes in their overall feature
      configuration but comprised different elements. These configurally similar scenes
      were used to limit explicit memory, and were intermixed with new scenes that did
      not resemble studied scenes. Scene configuration memory was expressed through eye
      movements reflecting exploration overlap (EO), which is the viewing of the same
      scene locations at both study and test. EO reliably discriminated similar study
      test scene pairs from study-new scene pairs, was reliably greater for similarity
      based recognition hits than for misses, and correlated with hippocampal fMRI
      activity. In contrast, subjects could not reliably discriminate similar from new
      scenes by overt judgments, although ratings of familiarity were slightly higher
      for similar than new scenes. Hippocampal fMRI correlates of this weak explicit
      memory were distinct from EO-related activity. These findings collectively
      suggest that EO was an implicit expression of scene configuration memory
      associated with hippocampal activity. Visual exploration can therefore reflect
      implicit hippocampal-related memory processing that can be observed in eye
      movement behavior during naturalistic scene viewing.

PMID- 25620528
TI  - Accuracy of hiatal hernia detection with esophageal high-resolution manometry.
AB  - BACKGROUND: The diagnosis of a sliding hiatal hernia is classically made with
      endoscopy or barium esophagogram. Spatial separation of the lower esophageal
      sphincter (LES) and diaphragm, the hallmark of hiatal hernia, can also be
      observed on high-resolution manometry (HRM), but the diagnostic accuracy of this
      finding has not yet been investigated. To determine the diagnostic value of HRM
      in the detection of hiatal hernia. METHODS: HRM recordings, endoscopy reports,
      and barium esophagograms of 90 patients were analyzed for the presence and size
      of a hiatal hernia. The diagnostic value of a hernia specific HRM pressure
      pattern was calculated, and the agreement of HRM with endoscopy and barium
      esophagogram for the assessment of hernia size. KEY RESULTS: HRM was found to be
      highly sensitive and specific for hiatal hernia detection, with a sensitivity of
      92% and specificity of 95%, exceeding the sensitivity of endoscopy or radiography
      alone (both 73%). Patients with a hiatal hernia on HRM were manometrically
      characterized by an esophagogastric junction (EGJ) with partial or complete
      separation of the LES and crural diaphragm (CD), the latter being associated with
      significantly lower EGJ pressure. A cutoff value of spatial LES-CD separation on
      HRM of 1.85 cm yielded the optimal performance in identifying hiatal hernia.
      Agreement between HRM, endoscopy, and radiography for size of hiatal hernias was
      good (ICC [95% CI] 0.74 [0.65-0.82]). CONCLUSIONS & INFERENCES: With HRM, the
      presence or absence and size of a hiatal hernia can be assessed with greater
      sensitivity than with endoscopy or radiography alone.

PMID- 25620529
TI  - Illuminating the future of silicon photonics: optical coupling of carbon
      nanotubes to microrings.
AB  - Advances in carbon nanotube material quality and processing techniques have led
      to an increased interest in nanotube photonics. In particular, emission in the
      telecommunication wavelengths makes nanotubes compatible with silicon photonics.
      Noury et al (2014 Nanotechnology 25 215201) have reported on carbon nanotube
      photoluminescence coupled to silicon microring resonators, underscoring the
      advantage of combining carbon nanotube emitters with silicon photonics. Their
      results open up the possibility of using nanotubes in other waveguide-based
      devices, taking advantage of well-established technologies. 

PMID- 25620530
TI  - Adherence to HIV care after pregnancy among women in sub-Saharan Africa: falling
      off the cliff of the treatment cascade.
AB  - Increased access to testing and treatment means HIV can be managed as a chronic
      illness, though successful management requires continued engagement with the
      health care system. Most of the global HIV burden is in sub-Saharan Africa where
      rates of new infections are consistently higher in women versus men. Pregnancy is
      often the point at which an HIV diagnosis is made. While preventing mother to
      child transmission (PMTCT) interventions significantly reduce the rate of
      vertical transmission of HIV, women must administer ARVs to their infants, adhere
      to breastfeeding recommendations, and test their infants for HIV after
      childbirth. Some women will be expected to remain on the ARVs initiated during
      pregnancy, while others are expected to engage in routine testing so treatment
      can be reinitiated when appropriate. The postpartum period presents many barriers
      to sustained treatment adherence and engagement in care. While some studies have
      examined adherence to postpartum PMTCT guidelines, few have focused on continued
      engagement in care by the mother, and very few examine adherence beyond the 6
      week postpartum visit. Here, we attempt to identify gaps in the research
      literature and make recommendations on how to address barriers to ongoing
      postpartum HIV care. 

PMID- 25620531
TI  - Transcranial magnetic stimulation of medial prefrontal cortex modulates implicit
      attitudes towards food.
AB  - The medial prefrontal cortex (mPFC) is known to be associated with food
      representation and monitoring of eating behaviour, but the neural mechanisms
      underlying attitudes towards food are still unclear. Transcranial magnetic
      stimulation (TMS) was used in combination with the implicit association test
      (IAT) to investigate the causal role of mPFC in controlling implicit food
      evaluation in healthy volunteers. Participants performed an IAT on tasty and
      tasteless food to test TMS interaction with food evaluation. Moreover, IATs
      assessing self-related concepts and attitude towards flowers and insects were
      carried out to control whether TMS could also affect self-representation or, more
      in general, the cognitive mechanisms required by the IAT. TMS was applied over
      mPFC; the left parietal cortex (lPA) was also stimulated as control site. Results
      revealed that mPFC-TMS selectively affected IAT on food, increasing implicit
      preference for tasty than tasteless food, only in a subgroup of participants who
      did not show extreme explicit evaluation for tasty and tasteless food. This
      demonstrates that mPFC has a critical causal role in monitoring food preference
      and highlights the relevance of considering individual differences in studying
      food representation and neural mechanisms associated with eating behaviour. 

PMID- 25620532
TI  - Surgical management of benign prostatic obstruction: current practice patterns
      and attitudes in Europe.

PMID- 25620533
TI  - Expression of microRNA-331 can be used as a predictor for response to therapy and
      survival in acute myeloid leukemia patients.
AB  - AIM: Aberrant expression of microRNAs (miRs) has been proved to have a role in
      acute myeloid leukemias (AML), but there is no information on miR-331 in AML.
      MATERIALS & METHODS: miR-331 expression has been analyzed using reverse
      transcription polymerase chain reaction (RT-PCR) in 95 bone marrow specimens from
      newly diagnosed AML patients in comparison with 20 healthy subjects. RESULTS: miR
      331 was upregulated in AML patients and its expression seemed to influence
      remission achieving and death risk. The time of remission duration in patients
      with complete remission was longer in subjects with miR-331 downregulation after
      induction chemotherapy. CONCLUSION: we showed for the first time that miR-331
      higher expression appears to be correlated with worse response to therapy and
      shorter survival of AML patients.

PMID- 25620534
TI  - HIF-1alpha induction, proliferation and glycolysis of Theileria-infected
      leukocytes.
AB  - Within 2 h of infection by Theileria annulata sporozoites, bovine macrophages
      display a two- to fourfold increase in transcription of hypoxia inducible factor
      (HIF-1alpha). Twenty hours post-invasion sporozoites develop into multi-nucleated
      macroschizonts that transform the infected macrophage into an immortalized,
      permanently proliferating, hyper-invasive and disease-causing leukaemia-like
      cell. Once immortalized Theileria-infected leukocytes can be propagated as cell
      lines and even though cultivated under normoxic conditions, both infected B cells
      and macrophages display sustained activation of HIF-1alpha. Attenuated
      macrophages used as live vaccines against tropical theileriosis also display HIF
      1alpha activation even though they have lost their tumorigenic phenotype. Here,
      we review data that ascribes HIF-1alpha activation to the proliferation status of
      the infected leukocyte and discuss the possibility that Theileria may have lost
      its ability to render its host macrophage virulent due to continuous parasite
      replication in a high Reactive Oxygen Species (ROS) environment. We propose a
      model where uninfected macrophages have low levels of H2 O2 output, whereas
      virulent-infected macrophages produce high amounts of H2 O2 . Further increase in
      H2 O2 output leads to dampening of infected macrophage virulence, a
      characteristic of disease-resistant macrophages. At the same time exposure to H2
      O2 sustains HIF-1alpha that induces the switch from mitochondrial oxidative
      phosphorylation to Warburg glycolysis, a metabolic shift that underpins
      uncontrolled infected macrophage proliferation. We propose that as macroschizonts
      develop into merozoites and infected macrophage proliferation arrests, HIF-1alpha
      levels will decrease and glycolysis will switch back from Warburg to oxidative
      glycolysis. As Theileria infection transforms its host leukocyte into an
      aggressive leukaemic-like cell, we propose that manipulating ROS levels, HIF
      1alpha induction and oxidative over Warburg glycolysis could contribute to
      improved disease control. Finally, as excess amounts of H2 O2 drive virulent
      Theileria-infected macrophages towards attenuation it highlights how infection
      induced pathology and redox balance are intimately linked. 

PMID- 25620535
TI  - Etifoxine versus alprazolam for the treatment of adjustment disorder with
      anxiety: a randomized controlled trial.
AB  - BACKGROUND: Adjustment disorder with anxiety (ADWA) is a highly prevalent
      condition, particularly in primary care practice. There are relatively few
      systematic treatment trials in the area of ADWA, and there are few data on
      predictors of treatment response. Etifoxine is a promising agent insofar as it is
      not associated with dependence, but in primary care settings benzodiazepines
      continue to be frequently prescribed for psychiatric symptoms. A randomized
      controlled trial of etifoxine versus alprazolam for ADWA was undertaken, focusing
      on efficacy and safety measures, and including an investigation of predictors of
      clinical response. METHODS: This was a comparative, multicenter, double-blind,
      randomized trial in two parallel groups of outpatients with ADWA. One group was
      treated with 150 mg/day for etifoxine, and the other with 1.5 mg/day for
      alprazolam for 28 days. Patients were followed for 4 weeks of treatment, and for
      an additional week after treatment discontinuation. The primary outcome measure
      was the Hamilton Anxiety Rating Scale (HAM-A), while secondary outcome measures
      included the Sheehan Disability Scale (SDS), the Clinical Global Impressions
      Change Scale (CGI-C), and the Self-Report for the Assessment of Adjustment
      Disorders. Non-inferiority analysis was used to assess the primary outcome
      measure, and a multivariate logistic regression was employed to investigate
      predictors of response. RESULTS: Two hundred and two adult outpatients with ADWA
      were enrolled at 17 primary care sites. One hundred and seventy seven patients
      completed the study (n = 87 in the etifoxine group; n = 90 in the alprazolam
      group). Etifoxine and alprazolam were accompanied by decreases in the HAM-A at
      day 28, with a difference between treatment groups in HAM-A score of 1.78 [90%
      CI; 0.23, 3.33] in favor of alprazolam. However, after medication
      discontinuation, HAM-A scores continued to improve in the etifoxine group, but
      increased in the alprazolam group; the difference between groups in mean change
      between day 28 and day 35 was significant (p = 0.019). Secondary outcome measures
      showed similar results for etifoxine and alprazolam at day 35. More treatment
      related adverse events were reported in patients treated with alprazolam,
      particularly central nervous system-related AEs, and especially after medication
      discontinuation. No significant predictors of treatment response were found.
      CONCLUSION: This randomized controlled trial provides support for the efficacy
      and safety of etifoxine in the management of adjustment disorder with anxiety,
      particularly when treatment discontinuation data are also assessed. Etifoxine has
      the important clinical advantage of having anxiolytic effects, which are not
      being associated with dependence. Pharmacotherapy was equally efficacious in
      patients with more severe anxiety symptoms at baseline. Additional work using
      longer-term follow-up and collecting data on cost-efficiency of management
      options would further advance the field of ADWA. FUNDING: Sponsorship and article
      processing charges for this study were provided by Biocodex, Gentilly, France.

PMID- 25620537
TI  - Use of inhaled tobramycin in cystic fibrosis.
AB  - Chronic infection with Pseudomonas aeruginosa is associated with poor outcomes in
      patients with cystic fibrosis (CF). It leads to a reduced quality of life,
      acceleration of the decline in lung function, and increased frequency and
      severity of pulmonary exacerbations. Tobramycin, administered by inhalation as a
      long-term therapy, decreases bacterial density in airways, reduces exacerbation
      frequency, and improves quality of life and lung function in patients with
      chronic P. aeruginosa infection. In the last decade, tobramycin inhalation has
      become an important contributor to CF treatment as a means to control chronic
      infection and as a first-line treatment for the eradication of early acquisition
      of P. aeruginosa. Recently, a dry powder inhalation (DPI) form of tobramycin has
      become available, which is more convenient for administration and has comparable
      efficacy to the tobramycin solution. This DPI, the PodhalerTM (Novartis
      Pharmaceuticals Corporation, East Hanover, NJ, USA), requires less time for
      treatment delivery and is more portable than a nebulizer, and so is a welcome
      additional therapeutic option for many patients. 

PMID- 25620536
TI  - Early direct and indirect impact of quadrivalent HPV (4HPV) vaccine on genital
      warts: a systematic review.
AB  - INTRODUCTION: Since 2007, many countries have implemented national human
      papillomavirus (HPV) vaccination programs with the quadrivalent HPV (4HPV)
      vaccine that has been shown to be efficacious in clinical trials involving 25,000
      subjects. Two vaccine serotypes, HPV16 and 18, are responsible for cervical
      cancer and other HPV-related cancers, but the impact of the 4HPV vaccine on these
      cancers cannot be seen immediately as there is a considerable lag between
      infection with HPV and cancer development. The other two serotypes, HPV6 and 11,
      are responsible for genital warts (GWs), which develop within a few months after
      infection, making GWs an early clinical endpoint for the assessment of the impact
      of 4HPV vaccination. METHODS: We performed a systematic literature search in
      PubMed to identify all published studies on 4HPV vaccination, including those
      that assessed the impact of 4HPV vaccination programs on the incidence of GWs at
      a population level around the world. RESULTS: A total of 354 records were
      identified in the PubMed search. After screening and obtaining full papers for 56
      publications, 16 publications presenting data on the impact or effectiveness of
      4HPV vaccination on GWs were identified. These reported data on the impact or
      effectiveness of 4HPV in six countries [Australia (n = 6), New Zealand (n = 2),
      United States (n = 3), Denmark (n = 2), Germany (n = 1), and Sweden (n = 2)]. In
      Australia, no GWs were diagnosed in women aged <21 years who reported being
      vaccinated. A 92.6% reduction in GWs incidence was reported for all women in this
      age group, where the vaccine uptake rate (VUR) was 70% for 3 doses. The highest
      reductions were reported in countries with high VURs, mostly through school-based
      vaccination programs, although high VURs were obtained with some non-school-based
      programs. CONCLUSION: The results are coherent with the GWs incidence reduction
      reported in clinical trials and are an early indicator of what can be expected
      for the long-term clinical impact on vaccine-type HPV-related cancers.

PMID- 25620538
TI  - Cost-effectiveness of point-of-care C-reactive protein tests for respiratory
      tract infection in primary care in England.
AB  - INTRODUCTION: Despite recommendations that general practitioners (GPs) delay
      antibiotic prescribing for respiratory tract infections (RTIs), antibiotic
      prescriptions in primary care in England increased by 4.1% from 2010 to 2013. C
      reactive protein (CRP) point-of-care tests (POCT), for example, the AfinionTM
      Analyzer (Alere Ltd, Stockport, UK) device, are widely used in several countries
      in the European Union. Studies suggest that CRP POCT use, either alone or in
      combination with communication training, reduces antibiotic prescribing and
      improves quality of life for patients presenting with RTI symptoms. The aim of
      this study is to evaluate the cost-effectiveness of CRP POCT for RTIs in primary
      care in England over 3 years for three different strategies of care compared to
      standard practice. METHODS: An economic evaluation was carried out to compare the
      costs and benefits of three different strategies of CRP testing (GP plus CRP;
      practice nurse plus CRP; and GP plus CRP and communication training) for patients
      with RTI symptoms as defined by National Institute for Health and Care Excellence
      guideline CG69, compared with current standard GP practice without CRP testing.
      Analysis consisted of a decision tree and Markov model to describe the quality
      adjusted life years (QALYs) and cost per 100 patients, together with the number
      of antibiotic prescriptions and RTIs for each group. RESULTS: Compared with
      current standard practice, the GP plus CRP and practice nurse plus CRP test
      strategies result in increased QALYs and reduced costs, while the GP plus CRP
      testing and communication training strategy is associated with increased costs
      and reduced QALYs. Additionally, all three CRP arms led to fewer antibiotic
      prescriptions and infections over 3 years. CONCLUSION: The additional cost per
      patient of the CRP test is outweighed by the associated cost savings and QALY
      increment associated with a reduction in infections in the long term.

PMID- 25620539
TI  - Dr. Ira Greifer.

PMID- 25620540
TI  - A novel fabrication of a polymeric ionic liquid hybrid film modified electrode
      and its successful application to the electrogeneration of a superoxide anion in
      aqueous media.
AB  - A novel polymeric ionic liquid hybrid film-modified electrode, in which the
      electrode surface is coated with a hydrophobic hybrid material composed of an
      ionene polymer with quaternary ammonium sites in its polymeric backbone and ionic
      liquids, was fabricated by electropolymerization of N,N-dimethylaniline in a
      hydrophobic ionic liquid, which can be applied for the electrogeneration of a
      superoxide anion via one-electron reduction of O2 in aqueous media. 

PMID- 25620541
TI  - [Medical nutritional concepts for obesity].
AB  - BACKGROUND: Obesity results from a chronic positive energy balance. THERAPY: A
      reduction of energy intake is the first and most effective option for weight
      reduction. In recent years a variety of new nutritional concepts for weight loss
      have been developed and evaluated. Apart from the classical low-fat energy
      restricted diet, low carbohydrate and high protein diets have also been
      established. RESULTS: Comparative studies showed that weight loss depends on the
      extent of energy restriction rather than on macronutrient composition. Due to the
      high variability in dietary habits the management of obesity should be problem
      oriented and patient-centered.

PMID- 25620542
TI  - Isospora streperae n. sp. (Apicomplexa: Eimeriidae) from a grey currawong
      (Strepera versicolour plumbea) (Passeriformes: Artamidae) in Western Australia.
AB  - A new species, Isospora streperae n. sp., (Apicomplexa: Eimeriidae) is described
      from a single grey currawong bird (Strepera versicolour) (subspecies S. v.
      plumbea) in Western Australia. Sporulated oocysts (n = 32) are spherical to
      subspherical, with smooth colourless bilayered oocyst wall, 1.0 um thick (outer
      layer 0?8 um, inner 0.2 um thick). Oocyst with a polar granule, an oocyst
      residuum and two spheroidal to subspheroidal sporocysts. Oocyst length, 23.8
      (20.4-25.0) um; oocyst width, 22.5 (20.0-24.6) um; a shape index of 1.06, with
      Stieda, substieda bodies. Micropyle is absent. Sporocysts with compressed
      sporocyst residuum and four sporozoites. Sporocyst length, 14.4 (12.5-15.2) um;
      sporocyst width, 11.2 (10.6-14.0) um, sporocyst L/W ratio, 1.29. Necropsy of the
      bird identified haemorrhaging along the ileum and jejunum, which is where
      Isospora oocysts were also mostly detected. Molecular analysis was conducted at
      three loci; the 18S, 28S ribosomal RNA and the mitochondrial cytochrome oxidase
      (COI) gene. At the 18S locus, I. streperae n. sp. exhibited 99.5% and 99.4%
      similarity respectively to an Isospora sp. (MS-2003) from a Southern cape sparrow
      (Passer melanurus melanurus) and Isospora dovati from a domestic pigeon (Columba
      livia domestica). At the 28S locus, I. streperae n. sp. exhibited 96.9%
      similarity to an Isospora sp. (MS-2003) from a grosbeak starling (Scissirostrum
      dubium) and 95.8% similarity with the Isospora sp. (MS-2003) from a Southern cape
      sparrow. At the COI locus, I. streperae n. sp. exhibited 95.0% similarity to
      Isospora sp. from a yellow-necked mouse (Apodemus flavicollis) from the Czech
      Republic. Based on morphological and molecular data, this isolate is a new
      species of Isospora, which is named Isospora streperae n. sp. after its host, the
      grey currawong (Strepera versicolour plumbea).

PMID- 25620543
TI  - An overview of nanoparticles commonly used in fluorescent bioimaging.
AB  - This article gives an overview of the various kinds of nanoparticles (NPs) that
      are widely used for purposes of fluorescent imaging, mainly of cells and tissues.
      Following an introduction and a discussion of merits of fluorescent NPs compared
      to molecular fluorophores, labels and probes, the article assesses the kinds and
      specific features of nanomaterials often used in bioimaging. These include
      fluorescently doped silicas and sol-gels, hydrophilic polymers (hydrogels),
      hydrophobic organic polymers, semiconducting polymer dots, quantum dots, carbon
      dots, other carbonaceous nanomaterials, upconversion NPs, noble metal NPs (mainly
      gold and silver), various other nanomaterials, and dendrimers. Another section
      covers coatings and methods for surface modification of NPs. Specific examples on
      the use of nanoparticles in (a) plain fluorescence imaging of cells, (b) targeted
      imaging, (c) imaging of chemical species, and (d) imaging of temperature are
      given next. A final section covers aspects of multimodal imaging (such as
      fluorescence/nmr), imaging combined with drug and gene delivery, or imaging
      combined with therapy or diagnosis. The electronic supplementary information
      (ESI) gives specific examples for materials and methods used in imaging, sensing,
      multimodal imaging and theranostics such as imaging combined with drug delivery
      or photodynamic therapy. The article contains 273 references in the main part,
      and 157 references in the ESI. 

PMID- 25620545
TI  - Size-controllable synthesis of trimetallic RhPdPt island-shaped nanoalloys with
      enhanced electrocatalytic performance for ethanol oxidation in alkaline medium.
AB  - Size-controllable, high-yield, island-shaped RhPdPt trimetallic nanocrystals with
      sub-2.0 nm islands have been successfully synthesized through a facile aqueous
      solution approach. The results of X-ray diffraction (XRD), energy-dispersive X
      ray (EDX) line scanning and elemental mapping analysis showed the as-synthesized
      RhPdPt nanocrystals are alloy structures. These island-shaped RhPdPt trimetallic
      nanoalloys showed a composition-dependent electrocatalytic performance for
      ethanol oxidation in alkaline medium. Due to the special structure and
      intermetallic synergies, the Rh10Pd40Pt50 nanoalloys exhibited an enhanced
      catalytic activity and durability relative to island-shaped Pd50Pt50 bimetallic
      nanoalloys and commercial Pt black. The peak current density for Rh10Pd40Pt50
      nanoalloys was 1.81 and 1.38 times that for commercial Pt black and Pd50Pt50
      nanoalloys, respectively. In addition, the peak potential on Rh10Pd40Pt50
      nanoalloys decreased 42 mV relative to commercial Pt black and Pd50Pt50
      nanoalloys.

PMID- 25620544
TI  - Assessment of published models and prognostic variables in epithelial ovarian
      cancer at Mayo Clinic.
AB  - OBJECTIVES: Epithelial ovarian cancer (EOC) is an aggressive disease in which
      first line therapy consists of a surgical staging/debulking procedure and
      platinum based chemotherapy. There is significant interest in clinically
      applicable, easy to use prognostic tools to estimate risk of recurrence and
      overall survival. In this study we used a large prospectively collected cohort of
      women with EOC to validate currently published models and assess prognostic
      variables. METHODS: Women with invasive ovarian, peritoneal, or fallopian tube
      cancer diagnosed between 2000 and 2011 and prospectively enrolled into the Mayo
      Clinic Ovarian Cancer registry were identified. Demographics and known prognostic
      markers as well as epidemiologic exposure variables were abstracted from the
      medical record and collected via questionnaire. Six previously published models
      of overall and recurrence-free survival were assessed for external validity. In
      addition, predictors of outcome were assessed in our dataset. RESULTS: Previously
      published models validated with a range of c-statistics (0.587-0.827), though
      application of models containing variables which are not part of routine practice
      were somewhat limited by missing data; utilization of all applicable models and
      comparison of results are suggested. Examination of prognostic variables
      identified only the presence of ascites and ASA score to be independent
      predictors of prognosis in our dataset, albeit with marginal gain in prognostic
      information, after accounting for stage and debulking. CONCLUSIONS: Existing
      prognostic models for newly diagnosed EOC showed acceptable calibration in our
      cohort for clinical application. However, modeling of prospective variables in
      our dataset reiterates that stage and debulking remains the most important
      predictors of prognosis in this setting.

PMID- 25620546
TI  - Multiple sclerosis risk loci correlate with cervical cord atrophy and may explain
      the course of disability.
AB  - Genome-wide association studies (GWAS) underscore the genetic basis of multiple
      sclerosis (MS); however, only few of the newly reported genetic variations
      relevant in MS have been replicated or correlated for clinical/paraclinical
      phenotypes such as spinal cord atrophy in independent patient cohorts. We
      genotyped 141 MS patients for 58 variations reported to reach significance in
      GWAS. Expanded disability status scale (EDSS) and disease duration (DD) are
      available from regular clinical examinations. MRI included sagittal high
      resolution 3D T1-weighted magnetization-prepared rapid acquisition gradient echo
      of the cervical cord region used for volumetry. Due dependency of mean upper
      cervical cord area (MUCCA) with EDSS and/or DD, correction operations were
      performed compensating for EDSS/DD. We assessed each MS risk locus for possible
      MUCCA association. We identified twelve risk loci that significantly correlated
      with MUCCA. For nine loci-BATF, CYP27B1, IL12B, NFKB1, IL7, PLEK, EVI5, TAGAP and
      nrs669607-patients revealed significantly higher degree of atrophy; TYK2, RGS1
      and CLEC16A revealed inverse effects. The weighted genetic risk score over the
      twelve loci showed significant correlation with MUCCA. Our data reveal a risk
      gene depending paraclinical/clinical phenotype. Since MUCCA clearly correlates
      with disability, the candidates identified here may serve as prognostic markers
      for disability progression. 

PMID- 25620547
TI  - Enhanced bioavailability of lycopene when consumed as cis-isomers from tangerine
      compared to red tomato juice, a randomized, cross-over clinical trial.
AB  - SCOPE: Tangerine tomatoes (Solanum lycopersicum) are rich in tetra-cis-lycopene
      resulting from natural variation in carotenoid isomerase. Our objective was to
      compare the bioavailability of lycopene from tangerine to red tomato juice, and
      elucidate physical deposition forms of these isomers in tomatoes by light and
      electron microscopy. METHODS AND RESULTS: Following a randomized cross-over
      design, subjects (n = 11, 6 M/5 F) consumed two meals delivering 10 mg lycopene
      from tangerine (94% cis) or red tomato juice (10% cis). Blood was sampled over 12
      h and triglyceride-rich lipoprotein fractions of plasma were isolated and
      analyzed using HPLC-DAD-MS/MS. Lycopene was crystalline in red tomato
      chromoplasts and globular in tangerine tomatoes. With tangerine tomato juice we
      observed a marked 8.5-fold increase in lycopene bioavailability compared to red
      tomato juice (p < 0.001). Fractional absorption was 47.70 +/- 8.81% from
      tangerine and 4.98 +/- 1.92% from red tomato juices. Large heterogeneity was
      observed among subjects. CONCLUSION: Lycopene is markedly more bioavailable from
      tangerine than from red tomato juice, consistent with a predominance of cis
      lycopene isomers and presence in chromoplasts in a lipid dissolved globular
      state. These results justify using tangerine tomatoes as a lycopene source in
      studies examining the potential health benefits of lycopene-rich foods.

PMID- 25620548
TI  - MyD88 signaling in T cells directs IgA-mediated control of the microbiota to
      promote health.
AB  - Altered commensal communities are associated with human disease. IgA mediates
      intestinal homeostasis and regulates microbiota composition. Intestinal IgA is
      produced at high levels as a result of T follicular helper cell (TFH) and B cell
      interactions in germinal centers. However, the pathways directing host IgA
      responses toward the microbiota remain unknown. Here, we report that signaling
      through the innate adaptor MyD88 in gut T cells coordinates germinal center
      responses, including TFH and IgA+ B cell development. TFH development is
      deficient in germ-free mice and can be restored by feeding TLR2 agonists that
      activate T cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high
      affinity IgA targeting of the microbiota and fails to control the bacterial
      community, leading to worsened disease. Our findings identify that T cells
      converge innate and adaptive immune signals to coordinate IgA against the
      microbiota, constraining microbial community membership to promote symbiosis. 

PMID- 25620550
TI  - Reflections on motor unit number estimation.

PMID- 25620549
TI  - Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized
      proteins asymmetrically within and between cells.
AB  - Mycobacterium tuberculosis (Mtb) defends itself against host immunity and
      chemotherapy at several levels, including the repair or degradation of
      irreversibly oxidized proteins (IOPs). To investigate how Mtb deals with IOPs
      that can neither be repaired nor degraded, we used new chemical and biochemical
      probes and improved image analysis algorithms for time-lapse microscopy to reveal
      a defense against stationary phase stress, oxidants, and antibiotics--the
      sequestration of IOPs into aggregates in association with the chaperone ClpB,
      followed by the asymmetric distribution of aggregates within bacteria and between
      their progeny. Progeny born with minimal IOPs grew faster and better survived a
      subsequent antibiotic stress than their IOP-burdened sibs. ClpB-deficient Mtb had
      a marked recovery defect from stationary phase or antibiotic exposure and
      survived poorly in mice. Treatment of tuberculosis might be assisted by drugs
      that cripple the pathway by which Mtb buffers, sequesters, and asymmetrically
      distributes IOPs.

PMID- 25620551
TI  - Enhanced definitions of intimate partner violence for DSM-5 and ICD-11 may
      promote improved screening and treatment.
AB  - Nuanced, multifaceted, and content valid diagnostic criteria for intimate partner
      violence (IPV) have been created and can be used reliably in the field even by
      those with little-to-no clinical training/background. The use of such criteria
      such as these would likely lead to more reliable decision making in the field and
      more consistency across studies. Further, interrater agreement was higher than
      that usually reported for individual mental disorders. This paper will provide an
      overview of (a) IPV's scope and impact; (b) the reliable and valid diagnostic
      criteria that have been used and the adaptation of these criteria inserted in the
      latest Diagnostic and Statistical Manual of Mental Disorders (DSM) and another
      adaptation proposed for the forthcoming International Statistical Classification
      of Diseases and Related Health Problems (ICD); (c) suggestions for screening of
      IPV in primary care settings; (d) interventions for IPV; and (e) suggested steps
      toward globally accepted programs. 

PMID- 25620552
TI  - Extremely preterm birth affects boys more and socio-economic and neonatal
      variables pose sex-specific risks.
AB  - AIM: The early identification of at-risk extremely preterm (EPT) children could
      improve long-term outcomes. This study sought to investigate sex differences in
      developmental outcomes and to identify sex-specific predictors at two and a half
      years of age. METHODS: We assessed 217 boys and 181 girls born before 27-week
      gestation using the Bayley Scales of Infant and Toddler Development, third
      edition (Bayley-III), as a part of the Extremely Preterm Infants in Sweden Study.
      Sex-specific differences were calculated. Socio-economic, birth and neonatal
      factors were calculated separately for boys and girls using regression models.
      RESULTS: Girls scored significantly higher than boys on all Bayley-III indices.
      In both sexes, brain injury, long-term ventilator treatment and foreign-born
      mothers predicted lower scores. Receiving breast milk by hospital discharge
      predicted higher scores. Severe retinopathy of prematurity was the strongest
      predictor of cognitive and language deficits in boys. High parental education
      predicted higher cognitive and language scores in girls, whereas severe
      bronchopulmonary dysplasia was the strongest predictor of motor deficits.
      CONCLUSION: Extreme prematurity seems to affect boys more than girls. Socio
      economic and neonatal factors confer similar risks or protections on both sexes,
      but some variables pose sex-specific risks. An awareness of risk factors may
      provide the basis for treatment and follow-up guidelines.

PMID- 25620553
TI  - Hepatitis C as a risk factor for carotid atherosclerosis - a systematic review.
AB  - BACKGROUND: Observational studies on the association of chronic hepatitis C with
      carotid atherosclerosis have yielded varying results. In addition, previous
      related systematic reviews were limited in synthesis. By more careful selection
      and further synthesis, we summarize current body of evidence on the relationship
      between chronic hepatitis C and carotid atherosclerosis. METHODS: All published
      observational studies related to the topic identified by systematic searches of
      PubMed and Scopus were screened based on diagnosis of chronic hepatitis C and
      diagnosis and estimation of the risk of a carotid atherosclerosis-related
      outcome. Selected studies were subjected to quality assessment, and eligible
      studies were used in subsequent narrative and quantitative syntheses. RESULTS:
      The initial search identified 190 unique publications, which were narrowed by
      preliminary review to 16 potentially relevant original articles. After quality
      assessment, seven studies were eligible and were used in narrative synthesis.
      Five studies assessed the risk of increased carotid intimal media thickening
      using B mode ultrasonography; five studies assessed the risk of carotid plaque
      formation using B mode ultrasonography. Five of these studies were used in
      subsequent meta-analysis. The risk of a person with chronic hepatitis C
      developing carotid intimal media thickening is about 4.03 times the risk of an
      uninfected person. The risk of a person with chronic hepatitis C developing
      carotid plaque is about 3.94 times the risk of an uninfected person. CONCLUSION:
      Current evidence shows that hepatitis C virus (HCV) or factors associated with
      HCV infection can promote the occurrence and progression of carotid
      atherosclerosis.

PMID- 25620554
TI  - The effects of Tai-Chi in conjunction with thera-band resistance exercise on
      functional fitness and muscle strength among community-based older people.
AB  - AIMS AND OBJECTIVES: The aim of this study was to investigate the effects of Tai
      Chi in conjunction with thera-band resistance exercise on functional fitness and
      muscle strength in community-based older people. BACKGROUND: Tai-Chi is known to
      improve functional fitness in older people. Tai-Chi is usually performed with
      free hands without resistance training and usually focuses on training lower
      limbs. To date, no study has examined the use of Tai-Chi in conjunction with
      thera-band resistance exercise in this population. DESIGN: Cluster randomised
      trial design. METHODS: Older people at six senior day care centres in Taiwan were
      assigned to thera-band resistance exercise or control group using a cluster
      randomisation. The thera-band resistance exercise group (n = 48) received sixty
      minute thera-band resistance exercise twice weekly for a period of 16 weeks. The
      control group (n = 47) underwent routine activities in the day care centre,
      receiving no Tai-Chi or resistance exercise. RESULTS: After receiving the thera
      band resistance exercise, intervention participants displayed a significant
      increase in muscle strength of upper and lower extremities. Significant
      improvements were recorded on most measures of the Senior Fitness Test, with the
      exception of the chair-stand and back-scratch test. CONCLUSION: Thera-band
      resistance exercise has the potential to improve functional fitness and muscle
      strength in community-based older people. RELEVANCE TO CLINICAL PRACTICE: Thera
      band resistance exercise potentially offers a safe and appropriate form of
      physical activity that nursing staff can easily incorporate into the daily
      routine of older people in day care centres, potentially improving functional
      performance and muscle strength.

PMID- 25620555
TI  - Anomalous excitonic resonance Raman effects in few-layered MoS2.
AB  - The resonance effects on the Raman spectra from 5 to 900 cm(-1) of few-layered
      MoS2 thin films up to 14-layers were investigated by using six excitation
      energies. For the main first-order Raman peaks, the intensity maximum occurs at
      ~2.8 eV for single layered and at ~2.5 eV for few-layered MoS2, which correspond
      to the band-gap energy. At the excitation energy of 1.96 eV, several anomalous
      behaviors are observed. Many second-order peaks are anomalously enhanced even
      though the main first-order peaks are not enhanced. In the low-frequency region
      (<100 cm(-1)), a broad peak centered at ~38 cm(-1) and its second order peak at
      76 cm(-1) appear for the excitation energy of 1.96 eV. These anomalous resonance
      effects are interpreted as occuring due to the strong resonance with excitons or
      exciton-polaritons. 

PMID- 25620556
TI  - ["Mechanic's hands" during antisynthetase syndrome: a marker of systemic
      involvement?].
AB  - BACKGROUND: Antisynthetase syndrome is characterized by the presence of
      interstitial lung disease, inflammatory myopathy, joint disease, Raynaud's
      phenomenon and characteristic skin lesions of the hands known as "mechanic's
      hands" associated with the presence of serum antibody to aminoacyl transfer-RNA
      synthetases. We report the case of a patient in whom cutaneous relapse
      consistently preceded CT evidence of pulmonary fibrosis flare-up. PATIENT AND
      METHODS: A 56-year-old patient consulted for recent exertional dyspnoea and dry
      cough. Clinical examination showed the skin of the tips and edges of the fingers
      to be thickened, hyperkeratotic and fissured. High-resolution computed tomography
      thoracic scans revealed interstitial lung lesions affecting both lower lobes. Lab
      tests showed elevated serum creatine kinase and positivity for anti-Jo-1
      antibodies. Response to treatment with corticosteroids and cyclophosphamide was
      marked by an improvement in symptoms and regression of radiological anomalies
      together with disappearance of cutaneous signs. Nine months later, after
      changeover from cyclophosphamide to mycophenolate mofetil, cutaneous relapse and
      flare of interstitial lung disease were observed. A second course of
      cyclophosphamide followed by azathioprine resulted in regression of the cutaneous
      and pulmonary lesions. CONCLUSION: Mechanic's hands may be considered a marker of
      visceral involvement and should be sought in any instance of suspected
      antisynthetase syndrome flare-up.

PMID- 25620557
TI  - Tuberculosis in the African continent: A comprehensive review.
AB  - Tuberculosis continues to be a major global health problem, causing an estimated
      8.8 million new cases and 1.45 million deaths annually. New drugs in the 1940s
      made it possible to beat the disease, and consequently, the number of cases
      reduced drastically. Fast-forward a few decades, drugresistant strains of varied
      virulence are reported consistently, disease is again on the rise and the
      treatment has not kept pace. Tuberculosis is the leading cause of death among HIV
      infected persons in many resource-constrained settings however, it is curable and
      preventable. The unprecedented growth of the tuberculosis epidemic in Africa is
      attributable to several factors, the most important being the HIV epidemic.
      Analysis of molecular-based data have shown diverse genetic backgrounds among
      both drug-sensitive and MDR TB isolates in Africa presumably due to underlying
      genetic and environmental differences. The good news is that there have been
      important advances recently in TB drugs and diagnostics. Despite the availability
      of revolutionary tests that allow for faster diagnosis and of new drugs and
      regimens that offer better and safer treatment it is now becoming clearer that
      national efforts on TB control should be enhanced and focus on improving the
      quality of prevention, diagnosis, treatment and care services; strengthening
      program management, implementation and supervision. This review is an assessment
      of the trend in TB in Africa. 

PMID- 25620558
TI  - TRF2 recruits RTEL1 to telomeres in S phase to promote t-loop unwinding.
AB  - The helicase RTEL1 promotes t-loop unwinding and suppresses telomere fragility to
      maintain the integrity of vertebrate telomeres. An interaction between RTEL1 and
      PCNA is important to prevent telomere fragility, but how RTEL1 engages with the
      telomere to promote t-loop unwinding is unclear. Here, we establish that the
      shelterin protein TRF2 recruits RTEL1 to telomeres in S phase, which is required
      to prevent catastrophic t-loop processing by structure-specific nucleases. We
      show that the TRF2-RTEL1 interaction is mediated by a metal-coordinating C4C4
      motif in RTEL1, which is compromised by the Hoyeraal-Hreidarsson syndrome (HHS)
      mutation, RTEL1(R1264H). Conversely, we define a TRF2(I124D) substitution
      mutation within the TRFH domain of TRF2, which eliminates RTEL1 binding and
      phenocopies the RTEL1(R1264H) mutation, giving rise to aberrant t-loop excision,
      telomere length heterogeneity, and loss of the telomere as a circle. These
      results implicate TRF2 in the recruitment of RTEL1 to facilitate t-loop
      disassembly at telomeres in S phase.

PMID- 25620559
TI  - Ubiquitin-dependent lysosomal membrane protein sorting and degradation.
AB  - As an essential organelle in the cell, the lysosome is responsible for digestion
      and recycling of intracellular components, storage of nutrients, and pH
      homeostasis. The lysosome is enclosed by a special membrane to maintain its
      integrity, and nutrients are transported across the membrane by numerous
      transporters. Despite their importance in maintaining nutrient homeostasis and
      regulating signaling pathways, little is known about how lysosomal membrane
      protein lifetimes are regulated. We identified a yeast vacuolar amino acid
      transporter, Ypq1, that is selectively sorted and degraded in the vacuolar lumen
      following lysine withdrawal. This selective degradation process requires a
      vacuole anchored ubiquitin ligase (VAcUL-1) complex composed of Rsp5 and Ssh4. We
      propose that after ubiquitination, Ypq1 is selectively sorted into an
      intermediate compartment. The ESCRT machinery is then recruited to sort the
      ubiquitinated Ypq1 into intraluminal vesicles (ILVs). Finally, the compartment
      fuses with the vacuole and delivers ILVs into the lumen for degradation. 

PMID- 25620561
TI  - Cryo-EM structure of influenza virus RNA polymerase complex at 4.3 A resolution.
AB  - Replication and transcription of influenza virus genome mainly depend on its RNA
      dependent RNA polymerase (RdRP), composed of the PA, PB1, and PB2 subunits.
      Although extensively studied, the underlying mechanism of the RdRP complex is
      still unclear. Here we report the biochemical characterization of influenza RdRP
      subcomplex comprising PA, PB1, and N terminus of PB2, which exist as dimer in
      solution and can assemble into a tetramer state, regulated by vRNA promoter.
      Using single-particle cryo-electron microscopy, we have reconstructed the RdRP
      tetramer complex at 4.3 A, highlighting the assembly and interfaces between
      monomers within the tetrameric structure. The individual RdRP subcomplex contains
      all the characterized motifs and appears as a cage-like structure. High
      throughput mutagenesis profiling revealed that residues involved in the oligomer
      state formation are critical for viral life cycle. Our results lay a solid base
      for understanding the mechanism of replication of influenza and other negative
      stranded RNA viruses. 

PMID- 25620562
TI  - Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA
      polymerase II CTD kinase.
AB  - DYRK1A is a dosage-sensitive protein kinase that fulfills key roles during
      development and in tissue homeostasis, and its dysregulation results in human
      pathologies. DYRK1A is present in both the nucleus and cytoplasm of mammalian
      cells, although its nuclear function remains unclear. Genome-wide analysis of
      DYRK1A-associated loci reveals that the kinase is recruited preferentially to
      promoters of genes actively transcribed by RNA polymerase II (RNAPII), which are
      functionally associated with translation, RNA processing, and cell cycle. DYRK1A
      bound promoter sequences are highly enriched in a conserved palindromic motif,
      which is necessary to drive DYRK1A-dependent transcriptional activation. DYRK1A
      phosphorylates the C-terminal domain (CTD) of RNAPII at Ser2 and Ser5. Depletion
      of DYRK1A results in reduced association of RNAPII at the target promoters as
      well as hypophosphorylation of the RNAPII CTD along the target gene bodies. These
      results are consistent with DYRK1A being a transcriptional regulator by acting as
      a CTD kinase. 

PMID- 25620560
TI  - The bacterial curli system possesses a potent and selective inhibitor of amyloid
      formation.
AB  - Curli are extracellular functional amyloids that are assembled by enteric
      bacteria during biofilm formation and host colonization. An efficient secretion
      system and chaperone network ensures that the major curli fiber subunit, CsgA,
      does not form intracellular amyloid aggregates. We discovered that the
      periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid
      formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In
      vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations
      and maintained CsgA in a non-beta-sheet-rich conformation. Interestingly, CsgC
      inhibited amyloid assembly of human alpha-synuclein, but not Abeta42, in vitro.
      We identified a common D-Q-Phi-X0,1-G-K-N-zeta-E motif in CsgC client proteins
      that is not found in Abeta42. CsgC is therefore both an efficient and selective
      amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature
      that distinguishes functional amyloids from disease-associated amyloids.

PMID- 25620563
TI  - The Hsp104 N-terminal domain enables disaggregase plasticity and potentiation.
AB  - The structural basis by which Hsp104 dissolves disordered aggregates and prions
      is unknown. A single subunit within the Hsp104 hexamer can solubilize disordered
      aggregates, whereas prion dissolution requires collaboration by multiple Hsp104
      subunits. Here, we establish that the poorly understood Hsp104 N-terminal domain
      (NTD) enables this operational plasticity. Hsp104 lacking the NTD
      (Hsp104(DeltaN)) dissolves disordered aggregates but cannot dissolve prions or be
      potentiated by activating mutations. We define how Hsp104(DeltaN) invariably
      stimulates Sup35 prionogenesis by fragmenting prions without solubilizing Sup35,
      whereas Hsp104 couples Sup35 prion fragmentation and dissolution. Volumetric
      reconstruction of Hsp104 hexamers in ATPgammaS, ADP-AlFx (hydrolysis transition
      state mimic), and ADP via small-angle X-ray scattering revealed a peristaltic
      pumping motion upon ATP hydrolysis, which drives directional substrate
      translocation through the central Hsp104 channel and is profoundly altered in
      Hsp104(DeltaN). We establish that the Hsp104 NTD enables cooperative substrate
      translocation, which is critical for prion dissolution and potentiated
      disaggregase activity.

PMID- 25620564
TI  - Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell
      Differentiation.
AB  - Polycomb Group (PcG) proteins maintain transcriptional repression throughout
      development, mostly by regulating chromatin structure. Polycomb Repressive
      Complex 2 (PRC2), a component of the Polycomb machinery, is responsible for the
      methylation of histone H3 lysine 27 (H3K27me2/3). Jarid2 was previously
      identified as a cofactor of PRC2, regulating PRC2 targeting to chromatin and its
      enzymatic activity. Deletion of Jarid2 leads to impaired orchestration of gene
      expression during cell lineage commitment. Here, we reveal an unexpected
      crosstalk between Jarid2 and PRC2, with Jarid2 being methylated by PRC2. This
      modification is recognized by the Eed core component of PRC2 and triggers an
      allosteric activation of PRC2's enzymatic activity. We show that Jarid2
      methylation is important to promote PRC2 activity at a locus devoid of H3K27me3
      and for the correct deposition of this mark during cell differentiation. Our
      results uncover a regulation loop where Jarid2 methylation fine-tunes PRC2
      activity depending on the chromatin context. 

PMID- 25620565
TI  - Anti-N-Methyl-D-Aspartate Receptor Encephalitis Presenting With Intermittent
      Catatonia.

PMID- 25620566
TI  - Physical disease and resilient outcomes: a systematic review of resilience
      definitions and study methods.
AB  - BACKGROUND: Findings from physical disease resilience research may be used to
      develop approaches to reduce the burden of disease. However, there is no
      consensus on the definition and measurement of resilience in the context of
      physical disease. OBJECTIVE: The aim was to summarize the range of definitions of
      physical disease resilience and the approaches taken to study it in studies
      examining physical disease and its relationship to resilient outcomes. METHODS:
      Electronic databases were searched from inception to March 2013 for studies in
      which physical disease was assessed for its association with resilient outcomes.
      Article screening, data extraction, and quality assessment were carried out
      independently by 2 reviewers, with disagreements being resolved by a third
      reviewer. The results were combined using a narrative technique. RESULTS: Of 2280
      articles, 12 met the inclusion criteria. Of these studies, 1 was of high quality,
      9 were of moderate quality, and 2 were low quality. The common findings were that
      resilience involves maintaining healthy levels of functioning following adversity
      and that it is a dynamic process not a personality trait. Studies either assessed
      resilience based on observed outcomes or via resilience measurement scales. They
      either considered physical disease as an adversity leading to resilience or as a
      variable modifying the relationship between adversity and resilience. CONCLUSION:
      This work begins building consensus as to the approach to take when defining and
      measuring physical disease resilience. Resilience should be considered as a
      dynamic process that varies across the life-course and across different domains,
      therefore the choice of a resilience measure should reflect this.

PMID- 25620567
TI  - Clinical and Sociodemographic Factors Associated With Attention
      Deficit/Hyperactivity Disorder in Patients With Cystic Fibrosis.
AB  - BACKGROUND: There is scarce evidence on the epidemiology of attention
      deficit/hyperactivity disorder (ADHD) in patients with cystic fibrosis (CF).
      OBJECTIVE: We employed stepwise logistic regression to examine the association
      between ADHD diagnosis and selected patient characteristics. METHODS: This was a
      cross-sectional analysis of inpatient and outpatient billing data for Medicaid
      beneficiaries with CF ages 3-18 years to obtain ADHD diagnosis prevalence and
      incidence estimates from 1999-2006. RESULTS: Annual ADHD prevalence increased
      1.55-fold from 5.26% (95% CI: 5.25-5.27) to 8.16% (8.15-8.17), and annual ADHD
      incidence rose slightly from 1.70% (1.70-1.71) to 2.01% (2.00-2.01). As in the
      general population, males were significantly more likely to have a diagnosis of
      ADHD compared with females (odds ratio: 1.97 [CI: 1.49-2.60]), as were children
      with recent diagnoses of anxiety, emotional disorder, depression, adjustment
      disorder, and learning, motor, and communication disorders. Patients with ADHD
      diagnoses were also more likely to be in foster care (odds ratio = 4.36 [CI: 2.26
      8.40]). Except for recent DNase use (odds ratio = 0.64 [CI: 0.43-0.93]), CF
      severity indicators and medications including pancreatic enzymes, inhaled
      tobramycin, inhaled or oral corticosteroids, inhaled bronchodilators, and oral
      antibiotics had no association with ADHD diagnosis. CONCLUSION: ADHD prevalence
      in CF increased during the study period. Clinical and sociodemographic
      determinants of ADHD diagnosis were similar to the general population, whereas
      treatment and severity of CF appeared to have little influence. Our findings
      warrant future research evaluating diagnostic protocols and assessment of safety
      and efficacy of ADHD treatment in children with CF.

PMID- 25620568
TI  - Alcohol Withdrawal Treatment in the Medically Hospitalized Patient: A Pilot Study
      Assessing Predictors for Medical or Psychiatric Complications.
AB  - BACKGROUND: Optimizing alcohol withdrawal treatment is a clinical priority, yet
      it is difficult to predict on presentation which patients would require
      benzodiazepines or in which patients withdrawal would be complicated.
      Detoxification studies typically exclude patients with medical comorbidities,
      psychiatric comorbidities, or multiple substance use disorders; therefore, it is
      difficult to generalize their conclusions to all types of patients. OBJECTIVE:
      This retrospective study with no exclusion criteria identifies the risk factors
      for complicated withdrawal. METHODS: A retrospective medical record review of 47
      veterans admitted to a tertiary veteran's medical hospital for alcohol
      detoxification. Demographics, blood alcohol level, Charlson Comorbidity Index,
      drinks per drinking day, pre-psychiatry consult benzodiazepine administration,
      and length of stay were compared for veterans with complications vs those
      without. RESULTS: Overall, 21% patients experienced significant complications
      during their medically-managed detoxification, including behavioral disruptions
      and delirium tremens. Of the patients, 79% were initially assessed using the
      Clinical Institute Withdrawal Assessment for Alcohol-Revised scale, and 34%
      continued to be monitored with the Clinical Institute Withdrawal Assessment for
      Alcohol-Revised scale during their hospital stay. A Clinical Institute Withdrawal
      Assessment for Alcohol-Revised scale score >=15 at presentation was significantly
      associated with increased odds of complications (p = 0.005). There was a trend
      toward significance of association of complications with tachycardia, history of
      delirium tremens, and benzodiazepines being administered before psychiatric
      consultation. The groups did not significantly differ with respect to age,
      admission blood alcohol level, Charlson Comorbidity Index, comorbid recent
      substance abuse, or length of stay. CONCLUSION: Clinical Institute Withdrawal
      Assessment for Alcohol-Revised scale scores >=15 at presentation was
      significantly associated with increased odds of complicated alcohol withdrawal
      (odds ratio = 28, 95% CI: 2.5-317.6, p = 0.005), which supports findings from
      previous studies.

PMID- 25620569
TI  - The catalytic domain of inositol-1,4,5-trisphosphate 3-kinase-a contributes to
      ITPKA-induced modulation of F-actin.
AB  - Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has been considered as an actin
      bundling protein because its N-terminal actin binding domain (ABD) induces
      formation of linear actin bundles. Since in many cancer cell lines ITPKA is
      essential for formation of lamellipodia, which consist of cross-linked actin
      filaments, here we analyzed if full length-ITPKA may induce formation of more
      complex actin structures. Indeed, we found that incubation of F-actin with ITPKA
      resulted in formation of dense, branched actin networks. Based on our result that
      ITPKA does not exhibit an additional C-terminal ABD, we exclude that ITPKA cross
      links actin filaments by simultaneous F-actin binding with two different ABDs.
      Instead, stimulated-emission-depletion-microscopy and measurement of InsP3 Kinase
      activity give evidence that that N-terminal ABD-homodimers of ITPKA bind to F
      actin while the monomeric C-termini insert between adjacent actin filaments.
      Thereby, they prevent formation of thick actin bundles but induce formation of
      thin branched actin structures. Interestingly, when embedded in this dense actin
      network, InsP3 Kinase activity is doubled and the product of InsP3 Kinase
      activity, Ins(1,3,4,5)P4 , inhibits spontaneous actin polymerization which may
      reflect a local negative feedback regulation of InsP3 Kinase activity. In
      conclusion, we demonstrate that not only the ABD of ITPKA modulates actin
      dynamics but reveal that the InsP3 Kinase domain substantially contributes to
      this process.

PMID- 25620570
TI  - Damnacanthal, a noni anthraquinone, inhibits c-Met and is a potent antitumor
      compound against Hep G2 human hepatocellular carcinoma cells.
AB  - Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine
      kinases and has antitumoral effects. This study aims at getting additional
      insight on the potential of damnacanthal as a natural antitumor compound. The
      direct effect of damnacanthal on c-Met was tested by in vitro activity assays.
      Additionally, Western blots of c-Met phosphorylation in human hepatocellular
      carcinoma Hep G2 cells were performed. The antitumor effects of damnacanthal were
      tested by using cell growth, soft agar clonogenic, migration and invasion assays.
      Their mechanisms were studied by Western blot, and cell cycle, apoptosis and
      zymographic assays. Results show that damnacanthal targets c-Met both in vitro
      and in cell culture. On the other hand, damnacanthal also decreases the
      phosphorylation levels of Akt and targets matrix metalloproteinase-2 secretion in
      Hep G2 cells. These molecular effects are accompanied by inhibition of the growth
      and clonogenic potential of Hep G2 hepatocellular carcinoma cells, as well as
      induction of Hep G2 apoptosis. Since c-Met has been identified as a new potential
      therapeutical target for personalized treatment of hepatocellular carcinoma,
      damnacanthal and noni extract supplements containing it could be potentially
      interesting for the treatment and/or chemoprevention of hepatocellular carcinoma
      through its inhibitory effects on the HGF/c-Met axis. 

PMID- 25620571
TI  - Congenital jaundice in bovine aborted foetuses: an emerging syndrome in southern
      Belgium.
AB  - Southern Belgium faces an unusual recent increase of icteric bovine aborted
      foetuses. In the necropsy room, the majority of foetuses presented jaundice and
      splenomegaly. Despite a wide range of analyses, no definitive cause of abortion
      has yet been established but some analysis results support the leptospirosis
      hypothesis. This first description of cases will help veterinary practitioners to
      recognize more cases and to conduct those to the laboratory for future
      investigations. 

PMID- 25620572
TI  - Luminescent organogels based on triphenylamine functionalized beta-diketones and
      their difluoroboron complexes.
AB  - A series of new triphenylamine functionalized beta-diketones 1-3 and their
      difluoroboron complexes 1B-3B were synthesized. They exhibited strong
      intramolecular charge transfer (ICT) emission. It was found that their self
      assembling properties depended on the molecular structures. For example,
      compounds 1 and 1B, in which only one beta-diketone or difluoroboron beta
      diketone unit was linked to triphenylamine, showed better gelation abilities
      directed by pi-pi interaction. Although bis-beta-diketone substituted
      triphenylamine 2 could not form organogels, its difluoroboron complex 2B could
      gel DMSO due to the strong dipole-dipole interactions. Compound 3 could form gels
      in polar solvents, while 3B formed gels in nonpolar solvents. Notably, the
      asymmetric gelators 1, 1B and 2B exhibited AIEE behaviors during the gelation.
      Although the emission of the symmetric compounds 3 and 3B decreased to a certain
      degree upon gelation, the obtained gels still gave strong emission. The gels
      formed from 1 and 3 emitted strong green light and those based on 1B-3B emitted
      strong orange or red light. These highly luminescent materials might have
      potential applications in emitting devices and fluorescent sensors.

PMID- 25620573
TI  - A carbon-air battery for high power generation.
AB  - We report a carbon-air battery for power generation based on a solid-oxide fuel
      cell (SOFC) integrated with a ceramic CO2-permeable membrane. An anode-supported
      tubular SOFC functioned as a carbon fuel container as well as an electrochemical
      device for power generation, while a high-temperature CO2-permeable membrane
      composed of a CO3(2-) mixture and an O(2-) conducting phase
      (Sm(0.2)Ce(0.8)O(1.9)) was integrated for in situ separation of CO2
      (electrochemical product) from the anode chamber, delivering high fuel
      utilization efficiency. After modifying the carbon fuel with a reverse Boudouard
      reaction catalyst to promote the in situ gasification of carbon to CO, an
      attractive peak power density of 279.3 mW cm(-2) was achieved for the battery at
      850  degrees C, and a small stack composed of two batteries can be operated
      continuously for 200 min. This work provides a novel type of electrochemical
      energy device that has a wide range of application potentials.

PMID- 25620574
TI  - Variability of total and free IgE levels and IgE receptor expression in allergic
      subjects in and out of pollen season.
AB  - The inter- and intra-individual variability and seasonal variation of IgE, and
      high (FcepsilonRI)- and low-affinity (CD23) IgE receptor expression in blood of
      seasonal allergic rhinitis (SAR) subjects, is not well studied. Thirty-two
      otherwise healthy subjects with a history of SAR to birch pollen and a positive
      skin prick test to birch pollen were sampled three times out of the pollen season
      and three times during the pollen season. FcepsilonRI and CD23 expressions were
      analysed using flow cytometry. Total IgE was analysed using ImmunoCAP((r)) and
      free IgE was analysed with a novel customised research assay using an IgG
      FcepsilonRI-chimera protein coupled to ImmunoCAP as capture reagent, ImmunoCAP
      specific IgE conjugate and ImmunoCAP IgE calibrators. The performance of the free
      IgE assay was compared well with the reference ImmunoCAP total IgE assay. The
      working range of the assay was 0.35-200 kU/l IgE. FcepsilonRI expression on
      basophils and CD23 expression on B cells showed low intrasubject variability both
      in and out of the pollen season (<10% CV). There was a small seasonal difference
      with lower total IgE levels (120 versus 128 kU/l; P = 0.004) and FcepsilonRI
      expression (283 versus 325 mean fluorescence intensity (MFI); P < 0.001) during
      the pollen season. IgE, FcepsilonRI expression and CD23 expression fulfilled
      biomarker and assay requirements of variability, and allergen exposure affected
      the biomarkers only to a minor degree. The free IgE assay may be used for
      measurement of free IgE levels in patients after anti-IgE antibody treatment.

PMID- 25620575
TI  - A new hypothesis of aging.
AB  - INTRODUCTION AND AIMS: There are over 300 hypotheses of aging, but none of them
      has enough predictive power to explain most experiments and observations on this
      process. On the basis of a critical analysis of the most relevant data on aging,
      especially on the factors that influences its rhythm, we present a new
      hypothesis, as well as the way the hypothesis' predictions explain some of the
      phylogenetic implications of the aging process. METHODS: The hypothesis starts
      from a new, biochemical view on evolution and the behavior of living matter.
      According to this view, life is a fabric of chemical reactions that sustain each
      other. Reactants and energy support are needed for these reactions to take place
      in a cell. Given this, aging stems from a leftward shift of the global
      equilibrium of some biochemical reactions involved in cell differentiation and
      repair, which take place at a high level during the organism's growth period. In
      time, for species with evident aging, some reactions lose their specificity,
      which affects cell division and differentiation. This, in turn, influences cell
      energy metabolism. RESULTS: Cell and tissue degeneration appears when, while some
      specific reactions are absent, non-specific reactions such as those of cell
      proliferation receive additional energy support. CONCLUSIONS: This hypothesis
      explains phylogenetic differences related to lifespan and longevity, and body
      size differences between species and within the same species.

PMID- 25620576
TI  - Cancer stem cells and mesenchymal stem cells in the hypoxic tumor niche: two
      different targets for one only drug.
AB  - Putative cancer stem cells (CSCs) reside in a hypoxic microenvironment where
      mesenchymal stem cells (MSCs) are also present. In this niche MSCs seem to
      promote the generation of CSCs and sustain tumor progression. Therefore, it may
      assume clinical relevance to produce a drug which kills not only CSCs but also
      MSCs. We hypothesized that bifunctional nanoparticles, loaded with a HIF-1alpha
      inhibitor and conjugated with an aptamer targeting a common receptor of CSCs and
      MSCs, may fulfill this strategy. The nanoparticle should ensure that: (1) the
      conveyed drug is less susceptible to degradation, (2) the common receptor of CSCs
      and MSCs is recognized by a superselective aptamer, and (3) receptor-mediated
      internalization is the main process to enter target cells. Small RNA or DNA
      aptamers represent an advantage over antibodies because do not cause immune
      reactions, are better internalized into the target cell, are more resistant to
      degradation, their cost of production are lower, and the purity of the
      oligonucleotide ligand is extremely elevated. Concerning the drugs to be
      delivered, we suggest to employ those exerting an anti-HIF-1alpha activity
      because they should be harmful for hypoxic CSCs and MCSs in their tumor niche but
      provide very limited toxicity, or even none, to well-oxygenated normal cells.
      Corresponding experimental approaches to perform pre-clinical studies and verify
      this hypothesis are also addressed. 

PMID- 25620578
TI  - The role of transbronchial cryobiopsy and surgical lung biopsy in the diagnostic
      algorithm of interstitial lung disease.
AB  - BACKGROUND AND AIMS: It is not yet known if transbronchial cryobiopsy (TCB) is a
      reliable and safe diagnostic tool in the investigation of interstitial lung
      disease (ILD). To date, there have been no studies directly comparing the value
      of TCB with that of surgical lung biopsy (SLB). The study was initiated to
      determine whether the samples taken by TCB lead to a reliable diagnosis and
      whether SLB can be avoided in a relevant percentage of cases. METHODS: We
      analyzed 32 subjects with suspected ILD who underwent a TCB. Subjects' baseline
      characteristics, pathological findings after TCB and SLB, and complication rates
      were analyzed. The pathological inter-rater agreement was quantified
      statistically. RESULTS: The overall inter-rater agreement concerning TCB sample
      evaluation was good with a kappa value of 0.80. In 23/32 cases (72%), the
      findings from the TCB showed a strong congruence with all other clinical data,
      thereby enabling a definitive diagnosis. Eight of the remaining nine subjects
      gave their consent for an SLB, which led to a definitive histological diagnosis
      in six cases (75%). Following TCB, pneumothorax occurred in 6/32 subjects (19%)
      and endobronchial bleeding was moderate in 8/32 (25%) and was severe in 17/32
      cases (53%). CONCLUSION: This is the first study to correlate histological
      results and complications following TCB and SLB in ILD subjects, some of whom
      underwent both procedures. TCB is a suitable diagnostic tool in ILD, potentially
      completely dispensing with the need for an SLB in some cases. In all cases, an
      interdisciplinary case evaluation is necessary as a final step.

PMID- 25620577
TI  - Risk of second malignancies in patients with early-stage classical Hodgkin's
      lymphoma treated in a modern era.
AB  - Second malignancies remain an issue affecting morbidity and mortality in long
      term survivors of early stage Hodgkin's lymphoma (HL). We undertook this study to
      determine if treatment in the modern era resulted in decreased second
      malignancies. Patients diagnosed with stage I-II cHL between 1988 and 2009 who
      received radiation therapy (RT) were selected from the Surveillance,
      Epidemiology, and End Results (SEER) database. Freedom from second malignancy
      (FFSM) was estimated using the Kaplan-Meier method. Univariate analysis (UVA) was
      performed using the Log-Rank test, and included age, gender, year of diagnosis,
      and stage. Multivariable analysis (MVA) was performed using Cox Proportional
      Hazards modeling. The study cohort included 8807 patients. The median age at
      diagnosis was 32 years (range: 2-85). The majority of patients had stage II
      disease (n = 6044, 69%), 597 (7%) had extranodal involvement (ENI), and 1925
      (22%) had B symptoms. Median follow-up for the entire cohort was 7.2 years
      (range: 0-22). Five hundred twenty-three (6%) patients developed a second
      malignancy. Median latency to second malignancy was 5.8 years (range: 0.1-21.5).
      Of the 523 patients that developed a second malignancy, 228 (44%) occurred in the
      first 5 years, 139 (27%) were diagnosed between years 5-10, and 156 (30%) beyond
      10 years. The 10 year FFSM for patients treated between 1988 and 1999 was 93.0%
      versus 95.1% for patients treated between 2000 and 2009 (P = 0.04), On MVA,
      treatment between 2000 and 2009 was associated with a HR for second malignancy of
      0.77 (95% Confidence Interval: 0.62-0.96, P = 0.02) compared to the treatment
      between 1988 and 1999. Our analysis suggests that in patients treated with RT for
      stage I or II cHL, treatment prior to 2000 had a slightly higher risk of second
      malignancy compared to treatment in 2000 and later. Further studies, with longer
      follow-up of patients treated in the modern era are needed to confirm these
      findings.

PMID- 25620579
TI  - Procedure-specific Cardiac Surgeon Volume associated with Patient outcome
      following Valve Surgery, but not Isolated CABG Surgery.
AB  - PURPOSE: Trends towards surgical sub-specialisation to improve patient-outcomes
      are well-documented and largely supported by evidence. However few studies have
      examined whether this benefit exists within adult-cardiac surgery. To answer
      whether sub-specialisation within adult-cardiac surgery improves patient
      outcomes, this study assessed the relationship between procedure-specific and
      total-cardiac surgeon-volume and mortality and morbidity in cardiac-valve and
      coronary artery bypass grafting (CABG) surgery. METHODS: Data came from the
      Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS)
      registry from 2001 to 2010 and included 23 hospitals, 109 surgeons, 20,619
      patients with isolated-CABG-surgery and 11,536 patients with a valve-procedure.
      Hierarchical logistic regression using generalised estimating equations was used
      to analyse outcomes. Measures included operative-mortality and occurrence of a
      complication (deep sternal wound infection, new stroke, acute kidney injury).
      RESULTS: Crude operative mortality (and complication rates) were 1.7% (4.9%) and
      4% (11%) in the isolated-CABG and valve-surgical populations respectively. A
      greater procedure-specific surgeon volume was associated with reduced mortality
      and complication rates in valve-surgery but not isolated-CABG. There was a 33%
      decrease in odds of dying for every additional 50 valve procedures performed [OR
      0.67, p=0.003]. Conversely, greater total-cardiac surgical volume for individual
      surgeons did not result in improved outcomes, for both isolated-CABG and valve
      populations. CONCLUSIONS: Our finding of an association between increased valve
      specific surgeon volumes with improved valve-surgery outcomes, and absence of an
      association between these outcomes and annual total-cardiac surgical experience
      supports the case for sub-specialisation specifically within the field of valve
      surgery.

PMID- 25620580
TI  - Postoperative assessment of hepatic asialoglycoprotein receptor function with Tc
      99m GSA: the safety margin of resection size in living donor liver
      transplantation.
AB  - BACKGROUND: Living liver donation is associated with size-dependent
      complications. The resectable size and its safety margin should be defined for
      the safety of donors. The purpose of the present study was to determine if the
      current partial hepatectomies are done under the safety margin of the resectable
      size, by measuring asialoglycoprotein receptor (ASGPR) function of donor's
      remnant liver. MATERIAL AND METHODS: Seventy-four living donors (age 35+/-11
      years) underwent Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl
      human serum albumin (Tc-99m GSA) scintigraphy at postoperative week 1. We
      evaluated the scintigraphic results using established parameters of GSA uptake
      (LHL15) and its clearance from the blood pool (HH15). Based on the literature, we
      consider HH15 <0.55 to indicate normal ASGPR function, and 0.55L HH15 <0.65 to
      indicate mild impairment. In terms of the hepatic uptake, we consider LHL15>0.93
      to indicate normal ASGPR function, and 0.87< LHL15 L0.93 to indicate mild
      impairment. RESULTS: The average resected size was 337+/-170 mL, corresponding to
      28+/-12% of the original donor's whole liver volume. No donors showed 0.65<= HH15
      or LHL15 <0.87, suggesting moderate or severely impaired ASGPR function. However,
      larger resection size (35-53%) was positively associated with higher HH15 values
      (R=0.53, p<0.001). In the range of HH15 (0.35-0.64) among present donors, higher
      HH15 values did not affect the regeneration volume (R=0.03, p=NS). CONCLUSIONS:
      Larger partial resection (>=35% of the original liver volume) may impair
      postsurgical ASGPR function, but smaller resection (<35%) was considered to be
      under the safety margin of the hepatectomy. Although mildly impaired postsurgical
      ASGPR function did not indicate poor prognosis, careful attention may be required
      for donors undergoing larger (335%) partial resection.

PMID- 25620581
TI  - Optically stimulated luminescence in LiCaAlF6:Eu2+ phosphor.
AB  - Results on optically stimulated luminescence (OSL) in LiCaAlF6:Eu(2+) are
      reported. Continuous wave OSL signal as recorded using blue (470 nm) stimulation
      was found to be ~31% that of standard phosphor lithium magnesium phosphate. The
      rate of OSL depletion for standard phosphor lithium magnesium phosphate is only
      three times less as compared with that of LiCaAlF6:Eu(2+). Strong
      photoluminescence (PL) in the near ultraviolet region is observed for
      LiCaAlF6:Eu(2+) with the characteristic Eu(2+) emission at 369 nm for 254 nm
      excitation. The thermoluminescence (TL) glow peak for LiCaAlF6:Eu(2+) was
      observed at around 180 degrees C. The glow peak was about six times more intense
      compared with the dosimetric peak of the well known thermoluminescence dosimetric
      (TLD) phosphor LiF-TLD 100. Thus this phosphor deserves much more attention than
      it has received until now and may be useful as a dosimetric material in radiation
      dosimetry.

PMID- 25620585
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1086/675995.]. 

PMID- 25620584
TI  - Central administration of GPR55 receptor agonist and antagonist modulates anxiety
      related behaviors in rats.
AB  - G-protein-coupled receptor 55 (GPR55) has been proposed as an atypical
      cannabinoid receptor, which is activated by lysophosphatidylinositols and some
      synthetic or endogenous cannabinoid molecules. The exact role of GPR55 receptors
      in the central nervous system especially in anxiety needs to be evaluated. In
      this study, the effects of intracerebroventricular (i.c.v.) administration of
      agonist and antagonist of GPR55 receptor on anxiety-related behaviors in rats
      were investigated. Here, O-1602 (GPR55 agonist) at the doses of 0.2, 1, and 5
      MUg/rat increased %OAT and %OAE but not the locomotor activity, showing an
      anxiolytic response, whereas i.c.v. injection of ML193 (GPR55 antagonist) at the
      doses of 0.1 and 1 MUg/rat increased anxiety-like behaviors while causing
      locomotor impairment. The antagonistic effect of ML193 on the anxiolytic-like
      effect of O-1602 was also evaluated. The results showed that ML193 decreased the
      anxiolytic-like effect of O-1602. Based on these results, it may be concluded
      that central GPR55 may have a role in modulation of anxiety-like behaviors in
      rats. Further experiments are needed to elucidate the exact role of these
      receptors in anxiety. 

PMID- 25620586
TI  - The effect of pomegranate fruit extract on testosterone-induced BPH in rats.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) affects many men after the age of
      50 years. Inflammation and oxidative stress along with apoptotic changes are
      thought to play an important role in the pathology of BPH. Pomegranate contains a
      variety of polyphenolic compounds that have been studied in a medley of diseases
      for their anti-oxidant, anti-inflammatory and pro-apoptotic properties.
      Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on
      the development of BPH using a testosterone-induced BPH model in rats. METHODS: A
      total of 48 rats were randomly divided into six groups of eight, one group served
      as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four
      groups, three of them received PFE by oral gavage daily at doses of 25, 50, and
      100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg
      without induction of BPH. RESULTS: PFE at a dose of 100 mg/kg was the most
      effective in decreasing testosterone-induced increase in prostate weight,
      prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68%
      respectively and in preventing the accompanying histological changes. In the BPH
      model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and
      0.88 of the control group values respectively, and significantly increased MDA by
      >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly
      increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values
      respectively, whereas MDA was significantly decreased by 72% compared with the
      testosterone treated group. In addition to this, at the range of doses studied,
      PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index.
      CONCLUSION: The current findings elucidate the effectiveness of PFE in preventing
      testosterone-induced BPH in rats. This could be attributed, at least partly, to
      its anti-oxidant, anti-inflammatory, and pro-apoptotic properties.

PMID- 25620587
TI  - Cyclic nucleotide phosphodiesterase-1C (PDE1C) drives cell proliferation,
      migration and invasion in glioblastoma multiforme cells in vitro.
AB  - Cyclic nucleotides (cAMP & cGMP) are critical intracellular second messengers
      involved in the transduction of a diverse array of stimuli and their catabolism
      is mediated by phosphodiesterases (PDEs). We previously detected focal genomic
      amplification of PDE1C in >90 glioblastoma multiforme (GBM) cells suggesting a
      potential as a novel therapeutic target in these cells. In this report, we show
      that genomic gain of PDE1C was associated with increased expression in low
      passage GBM-derived cell cultures. We demonstrate that PDE1C is essential in
      driving cell proliferation, migration and invasion in GBM cultures since
      silencing of this gene significantly mitigates these functions. We also define
      the mechanistic basis of this functional effect through whole genome expression
      analysis by identifying down-stream gene effectors of PDE1C which are involved in
      cell cycle and cell adhesion regulation. In addition, we also demonstrate that
      Vinpocetine, a general PDE1 inhibitor, can also attenuate proliferation with no
      effect on invasion/migration. Up-regulation of at least one of this gene set
      (IL8, CXCL2, FOSB, NFE2L3, SUB1, SORBS2, WNT5A, and MMP1) in TCGA GBM cohorts is
      associated with worse outcome and PDE1C silencing down-regulated their
      expression, thus also indicating potential to influence patient survival.
      Therefore we conclude that proliferation, migration, and invasion of GBM cells
      could also be regulated downstream of PDE1C.

PMID- 25620588
TI  - Clinical impact of the interval between chemoradiotherapy and esophagectomy in
      esophageal squamous cell carcinoma patients.
AB  - BACKGROUND: The optimal interval between chemoradiotherapy (CRT) and
      esophagectomy in patients with esophageal squamous cell carcinoma is still
      undetermined. The aim of this study was to evaluate the association between
      different treatment intervals and clinical impact, including perioperative
      outcome and long-term survival. METHODS: We retrospectively reviewed data from
      665 patients with esophageal squamous cell carcinoma who underwent CRT and
      esophagectomy between 2008 and 2011 in Taiwan. Based on the interval between CRT
      and esophagectomy, patients were divided into group 1, less than 30 days; group
      2, 30 to 59 days; group 3, 60 to 89 days; or group 4, 90 days or more. The impact
      of the treatment interval on perioperative outcomes and overall survival were
      assessed. A Cox regression model was used to identify prognostic factors for
      overall survival. RESULTS: There were 90 patients in group 1, 385 patients in
      group 2, 141 patients in group 3, and 49 patients in group 4. The 30-day surgical
      mortality rate was 5.6%, 2.9%, 1.4%, and 10.2% for groups 1, 2, 3, and 4,
      respectively (p = 0.018). The 90-day surgical mortality rate was 12.2%, 6.8%,
      5.7%, and 18.4% for groups 1, 2, 3, and 4, respectively (p = 0.012). The
      differences between surgical margin positivity rates were also significant: 2.2%
      in group 1, 4.9% in group 2, 9.2% in group 3, and 12.2% in group 4 (p = 0.032).
      The treatment interval was not associated with the complete response and the
      overall survival. CONCLUSIONS: Although early operation (less than 30 days) is
      associated with reduced rates of surgical margin positivity, the potential
      benefits appear to be outweighed by the significant increase in postoperative
      mortality. The surgical timing that optimizes both mortality and surgical margin
      positivity requires further study.

PMID- 25620589
TI  - Reversal of sympathetic interruption by removal of clips.
AB  - BACKGROUND: Sympathetic interruption offers excellent control of hyperhidrosis
      and facial blushing (FB), but some patients have side effects prompting a wish to
      reverse the procedure. Reversal when the chain has been cut is challenging,
      whereas reversal when the chain has been clipped is straightforward. The
      peripheral nerves regenerate; however, little is known about the regeneration of
      the sympathetic chain after clip removal. We reviewed our results with reversal
      of sympathetic interruption through removal of clips. METHODS: An institutional
      review board-approved retrospective review of patients treated for hyperhidrosis
      and FB from November 2004 to March 2014 was performed. We analyzed those patients
      undergoing sympathetic interruption with clips (N = 82). RESULTS: Eight patients
      (10%) requested and underwent reversal of the procedure between 12 days and 5.8
      years (median = 73.5 days) after the initial procedure. Compensatory sweating was
      the most frequent complaint (n = 6), and excessive palmar dryness was second (n =
      3), the latter occurring in patients without primary palmar hyperhidrosis. The
      interval between clip removal and follow-up ranged from 2 days to 4.5 years
      (median = 141 days). Five of 8 patients thus far have had their symptoms reversed
      through removal of clips (Table 1). CONCLUSIONS: The percentage of patients
      requesting reversal of sympathectomy is significant and appears to most commonly
      result from compensatory sweating (CS); however, excessive palmar dryness also
      occurs in those without primary palmar hyperhidrosis. It appears that the best
      results with reversal are obtained when the clips are removed early after
      placement. We counsel our patients that ideally clips should be removed within 2
      weeks for reversal.

PMID- 25620590
TI  - Solitary fibrous tumors of the pleura: a poorly defined malignancy profile.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical characteristics
      and factors that influence the long-term outcomes of solitary fibrous tumors of
      the pleura. METHODS: We conducted a retrospective study in 2 centers and reviewed
      80 patients who underwent surgery between May 1984 and April 2011. RESULTS: Of
      the 80 patients (29 male; median age, 60 years [33 to 85 years]), 47 were
      symptomatic (59%). The tumors originated from the visceral pleura in 62 cases
      (79%) and from the parietal pleura in 18 cases (22%). The tumors were
      pedunculated in 66 cases (83%) and sessile in 20 cases (17%). Surgical resection
      with histologically free margins was accomplished in 76 of 79 patients (93%). The
      tumors were classified as benign in 51 cases (65%) and as malignant in 28 (35%).
      The factors that were significantly associated with malignant tumors were the
      presence of symptoms (p = 0.03), a mean diameter 10 cm or greater (p = 0.0004),
      fibrous adherences (p = 0.003), pleural effusion (p = 0.003), and a Ki67 10% or
      greater (p = 0.003). The median follow-up was 69 months (range, 1 to 315). Local
      recurrence occurred in 3 cases. The overall 5- and 10-year survival rates were
      90% and 86%, respectively, and the mean survival time was 255 +/- 15 months.
      There were no differences between the benign and malignant tumors. CONCLUSIONS:
      The recurrence rates are low after surgeries for both benign and malignant
      solitary fibrous tumors of the pleura. However, the factors that are predictive
      of recurrence have yet to be specified and require additional immunohistochemical
      and genetic investigations.

PMID- 25620591
TI  - Regional myocardial three-dimensional principal strains during postinfarction
      remodeling.
AB  - BACKGROUND: The purpose of this study was to quantify myocardial three
      dimensional (3D) principal strains as the left ventricle (LV) remodels after
      myocardial infarction (MI). Serial quantification of myocardial strains is
      important for understanding the mechanical response of the LV to MI. Principal
      strains convert the 3D LV wall-based strain matrix with three normal and three
      shear elements, to a matrix with three nonzero normal elements, thereby
      eliminating the shear elements, which are difficult to physically interpret.
      METHODS: The study was designed to measure principal strains of the remote,
      border zone, and infarct regions in a porcine model of post-MI LV remodeling.
      Magnetic resonance imaging was used to measure function and strain at baseline, 1
      week, and 4 weeks after infarct. Principal strain was measured using 3D
      acquisition and the optical flow method for displacement tracking. RESULTS:
      Principal strains were altered as the LV remodeled. Maximum principal strain
      magnitude decreased in all regions, including the noninfarcted remote, while
      maximum principal strain angles rotated away from the radial direction in the
      border zone and infarct. Minimum principal strain magnitude followed a similar
      pattern; however, strain angles were altered in all regions. Evolution of
      principal strains correlated with adverse LV remodeling. CONCLUSIONS: Using a
      state-of-the-art imaging and optical flow method technique, 3D principal strains
      can be measured serially after MI in pigs. Results are consistent with
      progressive infarct stretching as well as with decreased contractile function in
      the border zone and remote myocardial regions.

PMID- 25620592
TI  - Coronary artery bypass revascularization using bilateral internal thoracic
      arteries in diabetic patients: a systematic review and meta-analysis.
AB  - This study examined the effect of coronary artery bypass graft surgery with
      bilateral internal thoracic artery grafting in diabetic patients. Coronary artery
      bypass graft surgery using skeletonized bilateral internal thoracic artery grafts
      was not associated with an increased risk of deep sternal wound infection or
      early death. Moreover, patients who underwent coronary artery bypass graft
      surgery using bilateral internal thoracic artery grafting had lower remote
      mortality and cardiac mortality. We conclude that coronary artery bypass surgery
      using bilateral internal thoracic artery grafts is an excellent strategy, even
      for diabetic patients. 

PMID- 25620593
TI  - A method to account for variation in congenital heart surgery charges.
AB  - BACKGROUND: In response to societal pressure to reduce expenditures and increase
      quality, we sought to develop a methodology to predict hospital charges related
      to congenital heart surgery. METHODS: Patients undergoing congenital heart
      surgery at Boston Children's Hospital in fiscal years 2007 to 2009 comprised the
      derivation cohort. Clinical data, including Current Procedural Terminology coding
      of the primary surgical intervention, were collected prospectively and linked to
      total hospital charges for an episode of care. Surgical charge categories were
      developed to group surgical procedure types using empiric data and expert
      consensus. A multivariable model was built using surgical charge categories and
      additional patient and procedural characteristics to predict the outcome, total
      hospital charges. A contemporary cohort for fiscal years 2010 to 2012 was used to
      validate surgical charge categories and the multivariable model. RESULTS: In the
      derivation cohort, 2,105 cases met inclusion criteria. One hundred three surgical
      procedure types were categorized into seven surgical charge categories, yielding
      a grouper variable with an R(2) explanatory value of 47.3%. Explanatory value
      increased with consideration of patient age, admission status, and preoperative
      ventilator dependence (R(2) = 59.4%), as well as weight category, noncardiac
      abnormality, and genetic syndrome other than trisomy 21 (R(2) = 61.5%).
      Additional variability in charge was explained when extracorporeal membrane
      oxygenation utilization and greater than one operating room visit during the
      episode of care were added (R(2) = 74.3%). The contemporary cohort yielded an
      R(2) explanatory value of 67.7%. CONCLUSIONS: The combination of clinical data
      with resource utilization information resulted in a statistically valid
      predictive model for total hospital charges in congenital heart surgery.

PMID- 25620594
TI  - Experience with biventricular intervention for neonates with mitral valve
      abnormalities in the setting of critical left-side heart obstruction.
AB  - BACKGROUND: Mitral valve (MV) abnormalities may adversely impact outcomes after
      biventricular repair of critical left-side heart obstruction. METHODS: Neonates
      with left-side heart obstruction and MV abnormality (anatomically abnormal or
      hypoplastic but otherwise normal [Z-score -1.5 to -4]) who underwent
      biventricular repair from December 2005 to December 2012 were included.
      Institutional selection criteria determined suitability for biventricular repair.
      Primary outcomes (death, univentricular conversion, pulmonary hypertension) and
      secondary outcomes (reinterventions) were compared between hypoplastic and
      anatomically abnormal MV groups. Freedom from reintervention was determined by
      Kaplan-Meier analysis. RESULTS: There were 55 patients with hypoplastic MV (n =
      35) or anatomically abnormal MV (n = 20). Initial interventions included arch
      repair (n = 45, with ventricular septal defect closure in 7), balloon aortic
      valvuloplasty (n = 8), and Ross-Konno operation (n = 2). None had initial MV
      intervention. Follow-up was available on 46 patients (84%) at a median of 25
      months. Primary outcome occurred in 6 patients (13%): 2 deaths, 1 univentricular
      conversion, and 3 pulmonary hypertension. Twenty-six patients (57%) underwent 36
      follow-up interventions, often for arch obstruction (n = 26). All follow-up MV
      interventions (n = 4) occurred in patients with anatomically abnormal MV. Median
      reintervention-free time was 7.3 months. Freedom from reintervention at 6, 9, and
      12 months was 65%, 38%, and 27%, respectively. Neither MV size nor anatomy was
      associated with primary outcome. CONCLUSIONS: Using our selection criteria, most
      neonates with left-side heart obstruction and MV abnormalities who underwent
      biventricular repair had reasonable survival with complex reintervention needs in
      early follow-up. The MV reintervention occurred in patients with abnormal
      anatomy, not hypoplasia.

PMID- 25620595
TI  - Psychoemotional and quality of life response to mitral operations in patients
      with mitral regurgitation: a prospective study.
AB  - BACKGROUND: Severe mitral regurgitation (MR) is associated with frequent
      alteration of psychoemotional status (PES), with anxiety and stress symptoms
      related to health-related quality of life (HR-QOL). Yet, it is unknown whether
      surgical correction of MR leads to improvement or deterioration in PES and HR
      QOL. METHODS: We prospectively performed comprehensive MR assessment and
      administered questionnaires assessing PES and HR-QOL in 131 patients (aged 60
      years; 75% men) before and 6 months after operation for organic MR and compared
      them to 62 patients who did not undergo operation for mitral disease and 36
      normal controls of similar age assessed with the same methods. RESULTS: Baseline
      PES was poorer preoperatively in patients undergoing mitral operation compared
      with patients who did not undergo mitral operation and normal controls (anxiety
      and posttraumatic stress [PTS]; both p < 0.01) with poorer physical HR-QOL (p <
      0.01). Six months later, all these psychoemotional variables improved (all p <=
      0.02) in the patients who underwent mitral operation, whereas no change was
      observed in the other 2 groups (all p > 0.1). Improvement after mitral repair
      resulted in postoperative normalization of emotional and physical well-being,
      with similar scores among all groups (all p >= 0.4). At 6-month follow-up, no
      difference in improvement in PES and HR-QOL was noted according to the surgical
      approach (robotic versus sternotomy, all p >= 0.2). CONCLUSIONS: Patients with
      severe organic MR present with frequent psychoemotional alterations and HR-QOL
      deterioration, in contrast to patients who do not undergo mitral operation and
      normal controls. After mitral operation, notable improvement results in
      normalization of emotional and physical well-being. Quantification of emotional
      and physical well-being provides important outcome measures in patients with
      organic MR and uncovers important benefits provided by surgical correction of MR.

PMID- 25620596
TI  - Relationship of single ventricle filling and preload to total cavopulmonary
      connection hemodynamics.
AB  - BACKGROUND: Single ventricle lesions are associated with gradual attrition after
      surgical palliation with the total cavopulmonary connection (TCPC). Ventricular
      dysfunction is frequently noted, particularly impaired diastolic performance.
      This study seeks to relate TCPC hemodynamic energy losses to single ventricle
      volumes and filling characteristics. METHODS: Cardiac magnetic resonance (CMR)
      data were retrospectively analyzed for 30 single ventricle patients at an average
      age of 12.7 +/- 4.8 years. Cine ventricular short-axis scans were
      semiautomatically segmented for all cardiac phases. Ventricular volumes, ejection
      fraction, peak filling rate, peak ejection rate, and time to peak filling were
      calculated. Corresponding patient-specific TCPC geometry was acquired from a
      stack of transverse CMR images; relevant flow rates were segmented from through
      plane phase contrast CMR data at TCPC inlets and outlets. The TCPC indexed power
      loss was calculated from computational fluid dynamics simulations using a
      validated custom solver. Time-averaged flow conditions and rigid vessel walls
      were assumed in all cases. Pearson correlations were used to detect relationships
      between variables, with p less than 0.05 considered significant. RESULTS:
      Ventricular end-diastolic (R = -0.48) and stroke volumes (R = -0.37) had
      significant negative correlations with the natural logarithm of a flow
      independent measure of power loss. This power loss measure also had a significant
      positive relationship to time to peak filling rate (normalized to cycle time; R =
      0.67). CONCLUSIONS: Flow-independent TCPC power loss is inversely related with
      ventricular end-diastolic and stroke volumes. Elevated power losses may
      contribute to impaired diastolic filling and limited preload reserve in single
      ventricle patients.

PMID- 25620597
TI  - Comparison of malignant grade between pure and partially invasive types of early
      lung adenocarcinoma.
AB  - BACKGROUND: The present study investigates the malignant significance of lepidic
      component presence in predominantly invasive lung adenocarcinoma that comprise
      less than 50% lepidic growth of the tumor. METHODS: Among 347 consecutive
      patients with completely resected clinical stage IA lung adenocarcinoma, we
      excluded those with adenocarcinoma in situ, minimally invasive, and lepidic
      predominant invasive adenocarcinoma. We finally assessed 167 patients with
      predominantly invasive lung adenocarcinoma. We analyzed the clinicopathologic
      characteristics and prognoses of patients with 49 pure invasive tumors without
      lepidic growth and 118 partially invasive tumors with lepidic growth. RESULTS:
      Pure invasive tumors were associated with being male, small tumor size, high
      maximum standardized uptake, and pleural as well as lymphatic invasion.
      Nonetheless, the invasive component size of both tumor types was similar. The
      predominant subtypes of pure and partially invasive tumors, respectively, were
      papillary, 17 (34.7%) and 53 (44.9%); acinar, 10 (20.4%) and 51 (43.2%); solid,
      19 (38.8%) and 11 (9.3%), and micropapillary 3 (6.1%) and 3 (2.5%; p < 0.001).
      Recurrence-free survival was significantly worse for patients with pure, compared
      with partially, invasive tumors (p = 0.045). CONCLUSIONS: Among predominantly
      invasive stage IA lung adenocarcinomas, the malignant potential was higher for
      pure invasive tumors, and the prognosis was poorer than for partially invasive
      tumors when the invasive components were of equal sizes. The presence or absence
      of a lepidic component reflects a difference in subtype predominance and can help
      to decide the malignant grade of lung adenocarcinoma.

PMID- 25620598
TI  - Surgically resected solitary cavitary lung adenocarcinoma: association between
      clinical, pathologic, and radiologic findings and prognosis.
AB  - BACKGROUND: The incidence of cavitary lung adenocarcinoma has recently increased;
      despite this, little is known about its clinical features and prognosis. We,
      therefore, evaluated the clinicopathologic features and prognosis of this
      malignancy. METHODS: Between 1998 and 2007, 2,316 patients without preoperative
      chemotherapy or radiation therapy underwent surgical resection for primary lung
      adenocarcinoma. Among these cases, 143 (6.2%) were diagnosed as having cavitary
      adenocarcinoma based on high-resolution computed tomography scans and were
      enrolled in our study. RESULTS: Cavitary adenocarcinoma occurred more frequently
      in patients who were male (p < 0.001); who had a smoking history (p < 0.001),
      larger tumor size (p < 0.001), a tumor in the lower lobe (p < 0.001), lymph node
      metastasis (p = 0.02), advanced tumor stage (p = 0.04), postoperative recurrence
      (p < 0.01), and a papillary (p = 0.02) or solid predominant tumor pattern (p <
      0.01); and who had vascular (p < 0.001), lymphatic (p = 0.04), or pleural
      invasion (p < 0.01). Kaplan-Meier analysis revealed that the overall and
      recurrence-free survival of patients with cavitary adenocarcinoma was
      significantly shorter than that of patients with noncavitary adenocarcinoma (p <
      0.001). Multivariate analysis revealed that cavity formation was an independent
      prognostic factor in adenocarcinoma (p = 0.028). CONCLUSIONS: Cavitary
      adenocarcinoma has worse prognostic clinicopathologic characteristics than
      noncavitary adenocarcinoma. Based on this finding, cavitary and noncavitary
      adenocarcinoma tumors should be considered separate entities.

PMID- 25620599
TI  - A landscape ecology approach identifies important drivers of urban biodiversity.
AB  - Cities are growing rapidly worldwide, yet a mechanistic understanding of the
      impact of urbanization on biodiversity is lacking. We assessed the impact of
      urbanization on arthropod diversity (species richness and evenness) and abundance
      in a study of six cities and nearby intensively managed agricultural areas.
      Within the urban ecosystem, we disentangled the relative importance of two key
      landscape factors affecting biodiversity, namely the amount of vegetated area and
      patch isolation. To do so, we a priori selected sites that independently varied
      in the amount of vegetated area in the surrounding landscape at the 500-m scale
      and patch isolation at the 100-m scale, and we hold local patch characteristics
      constant. As indicator groups, we used bugs, beetles, leafhoppers, and spiders.
      Compared to intensively managed agricultural ecosystems, urban ecosystems
      supported a higher abundance of most indicator groups, a higher number of bug
      species, and a lower evenness of bug and beetle species. Within cities, a high
      amount of vegetated area increased species richness and abundance of most
      arthropod groups, whereas evenness showed no clear pattern. Patch isolation
      played only a limited role in urban ecosystems, which contrasts findings from
      agro-ecological studies. Our results show that urban areas can harbor a similar
      arthropod diversity and abundance compared to intensively managed agricultural
      ecosystems. Further, negative consequences of urbanization on arthropod diversity
      can be mitigated by providing sufficient vegetated space in the urban area, while
      patch connectivity is less important in an urban context. This highlights the
      need for applying a landscape ecological approach to understand the mechanisms
      shaping urban biodiversity and underlines the potential of appropriate urban
      planning for mitigating biodiversity loss. 

PMID- 25620600
TI  - An impaired ubiquitin ligase complex favors initial growth of auxotrophic yeast
      strains in synthetic grape must.
AB  - We used experimental evolution in order to identify genes involved in the
      adaptation of Saccharomyces cerevisiae to the early stages of alcoholic
      fermentation. Evolution experiments were run for about 200 generations, in
      continuous culture conditions emulating the initial stages of wine fermentation.
      We performed whole-genome sequencing of four adapted strains from three
      independent evolution experiments. Mutations identified in these strains pointed
      to the Rsp5p-Bul1/2p ubiquitin ligase complex as the preferred evolutionary
      target under these experimental conditions. Rsp5p is a multifunctional enzyme
      able to ubiquitinate target proteins participating in different cellular
      processes, while Bul1p is an Rsp5p substrate adaptor specifically involved in the
      ubiquitin-dependent internalization of Gap1p and other plasma membrane permeases.
      While a loss-of-function mutation in BUL1 seems to be enough to confer a
      selective advantage under these assay conditions, this did not seem to be the
      case for RSP5 mutated strains, which required additional mutations, probably
      compensating for the detrimental effect of altered Rsp5p activity on essential
      cellular functions. The power of this experimental approach is illustrated by the
      identification of four independent mutants, each with a limited number of SNPs,
      affected within the same pathway. However, in order to obtain information
      relevant for a specific biotechnological process, caution must be taken in the
      choice of the background yeast genotype (as shown in this case for auxotrophies).
      In addition, the use of very stable continuous fermentation conditions might lead
      to the selection of a rather limited number of adaptive responses that would mask
      other possible targets for genetic improvement. 

PMID- 25620601
TI  - Phytotherapy as an alternative for treating fish disease.
AB  - Intensification of livestock rearing often promotes an increase in inappropriate
      practices that disregard care for the environment, animal health, and workers'
      health. Intensive fish farming systems are often associated with higher stocking
      density and massive use of artificial feed. Currently, outbreaks of parasitic,
      bacterial, and fungal diseases act as major limiting factors for fish farming,
      meaning that producers have to make use of massive amounts of antibiotics,
      disinfectants, and pesticides in order to control mortality and avoid huge
      economic losses. Because of adverse effects on the aquatic environment,
      terrestrial organisms, and human health (both fish handlers and consumers), this
      therapy has been criticized. Use of herbal medicines within animal production has
      shown promise, in that it is natural and biodegradable and has antimicrobial
      activity against various pathogens, including those relating to fish. Recently,
      researchers have reported promising effects from many herbal medicines for
      treating parasitic diseases caused by protozoa and metazoa, and broad activity
      against bacteria and fungi. This review addresses the current issues regarding
      indiscriminate use of chemicals and antibiotics in aquaculture and discusses the
      main findings and methodologies of the latest research on herbal medicines to
      stimulate and accelerate research in this field, especially in developing
      countries. 

PMID- 25620602
TI  - A power series beta Weibull regression model for predicting breast carcinoma.
AB  - The postmastectomy survival rates are often based on previous outcomes of large
      numbers of women who had a disease, but they do not accurately predict what will
      happen in any particular patient's case. Pathologic explanatory variables such as
      disease multifocality, tumor size, tumor grade, lymphovascular invasion, and
      enhanced lymph node staining are prognostically significant to predict these
      survival rates. We propose a new cure rate survival regression model for
      predicting breast carcinoma survival in women who underwent mastectomy. We assume
      that the unknown number of competing causes that can influence the survival time
      is given by a power series distribution and that the time of the tumor cells left
      active after the mastectomy for metastasizing follows the beta Weibull
      distribution. The new compounding regression model includes as special cases
      several well-known cure rate models discussed in the literature. The model
      parameters are estimated by maximum likelihood. Further, for different parameter
      settings, sample sizes, and censoring percentages, some simulations are
      performed. We derive the appropriate matrices for assessing local influences on
      the parameter estimates under different perturbation schemes and present some
      ways to assess local influences. The potentiality of the new regression model to
      predict accurately breast carcinoma mortality is illustrated by means of real
      data.

PMID- 25620603
TI  - Molecular phylogenetics and species delimitation of leaf-toed geckos
      (Phyllodactylidae: Phyllodactylus) throughout the Mexican tropical dry forest.
AB  - Methods and approaches for accurate species delimitation continue to be a highly
      controversial subject in the systematics community. Inaccurate assessment of
      species' limits precludes accurate inference of historical evolutionary
      processes. Recent evidence suggests that multilocus coalescent methods show
      promise in delimiting species in cryptic clades. We combine multilocus sequence
      data with coalescence-based phylogenetics in a hypothesis-testing framework to
      assess species limits and elucidate the timing of diversification in leaf-toed
      geckos (Phyllodactylus) of Mexico's dry forests. Tropical deciduous forests (TDF)
      of the Neotropics are among the planet's most diverse ecosystems. However, in
      comparison to moist tropical forests, little is known about the mode and tempo of
      biotic evolution throughout this threatened biome. We find increased speciation
      and substantial, cryptic molecular diversity originating following the formation
      of Mexican TDF 30-20million years ago due to orogenesis of the Sierra Madre
      Occidental and Mexican Volcanic Belt. Phylogenetic results suggest that the
      Mexican Volcanic Belt, the Rio Fuerte, and Isthmus of Tehuantepec may be
      important biogeographic barriers. Single- and multilocus coalescent analyses
      suggest that nearly every sampling locality may be a distinct species. These
      results suggest unprecedented levels of diversity, a complex evolutionary
      history, and that the formation and expansion of TDF vegetation in the Miocene
      may have influenced subsequent cladogenesis of leaf-toed geckos throughout
      western Mexico. 

PMID- 25620604
TI  - Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human
      alveolar epithelial cell line A549.
AB  - Man-made vitreous fibers have been widely used as insulation material as asbestos
      substitutes; however their morphology and composition raises concerns. In 1988
      the International Agency for Research on Cancer classified fiberglass, rock wool,
      slag wool, and ceramic fibers as Group 2B, i.e. possibly carcinogenic to humans.
      In 2002 it reassigned fiberglass, rock and slag wool, and continuous glass
      filaments to Group 3, not classifiable as carcinogenic to humans. The aim of this
      study was to verify the cytotoxic and genotoxic effects and oxidative stress
      production induced by in vitro exposure of human alveolar epithelial cells A549
      to glass fibers with a predominant diameter <3 MUm (97%) and length >5 MUm (93%).
      A549 cells were incubated with 5, 50, or 100 MUg/ml (2.1, 21, and 42 MUg/cm(2),
      respectively) of glass fibers for 72 h. Cytotoxicity and DNA damage were tested
      by the MTT and the Comet assay, respectively. Oxidative stress was determined by
      measuring inducible nitric oxide synthase (iNOS) expression by Western blotting,
      production of nitric oxide (NO) with Griess reagent, and concentration of
      reactive oxygen species by fluorescent quantitative analysis with 2',7'
      dichlorofluorescein-diacetate (DCFH-DA). The results showed that glass fiber
      exposure significantly reduced cell viability and increased DNA damage and
      oxidative stress production in a concentration-dependent manner, demonstrating
      that glass fibers exert cytotoxic and genotoxic effects related to increased
      oxidative stress on the human alveolar cell line A549.

PMID- 25620606
TI  - Exploration of the dynamics between brain regions associated with the default
      mode network and frontostriatal pathway with regards to task familiarity.
AB  - Specific brain regions have consistently been reported to be activated during
      resting state period, and they were described as being part of a particular
      network called the default-mode network (DMN). It has been shown that the DMN
      would deactivate during goal-directed tasks, but the actual relationship between
      them is still a matter of debate. In a previous study, we reported a specific
      pattern of activation of the frontostriatal regions during a set-shifting task in
      which these regions were increasing their activity as set-shifts were performed
      continuously and decreasing when the same rule was executed repeatedly. The
      present study aimed at assessing the relationship between the frontostriatal
      regions and the DMN. We hypothesized that the DMN would be anticorrelated with
      the frontostriatal regions so the DMN would be more deactivated as set-shifts are
      executed for a long period, but would start increasing when the same rule is
      being executed for a long period. Here, 15 participants underwent functional
      magnetic resonance imaging while performing a card-sorting task. We observed
      increased activity in the frontostriatal regions as more set-shifts are being
      performed while the DMN gets more deactivated. Interestingly, as decreased
      activity was observed in the frontostriatal regions during the execution of the
      same rule for a long period, the DMN showed increasing activity. We argue that
      there is an anticorrelation between the frontostriatal regions and the DMN, but
      also that the DMN could show positive activation during performance of a familiar
      goal-directed task. 

PMID- 25620605
TI  - Reduced availability of voltage-gated sodium channels by depolarization or
      blockade by tetrodotoxin boosts burst firing and catecholamine release in mouse
      chromaffin cells.
AB  - KEY POINTS: Mouse chromaffin cells (MCCs) of the adrenal medulla possess fast
      inactivating Nav channels whose availability alters spontaneous action potential
      firing patterns and the Ca(2+)-dependent secretion of catecholamines. Here, we
      report MCCs expressing large densities of neuronal fast-inactivating Nav1.3 and
      Nav1.7 channels that carry little or no subthreshold pacemaker currents and can
      be slowly inactivated by 50% upon slight membrane depolarization. Reducing
      Nav1.3/Nav1.7 availability by tetrodotoxin or by sustained depolarization near
      rest leads to a switch from tonic to burst-firing patterns that give rise to
      elevated Ca(2+)-influx and increased catecholamine release. Spontaneous burst
      firing is also evident in a small percentage of control MCCs. Our results
      establish that burst firing comprises an intrinsic firing mode of MCCs that
      boosts their output. This occurs particularly when Nav channel availability is
      reduced by sustained splanchnic nerve stimulation or prolonged cell
      depolarizations induced by acidosis, hyperkalaemia and increased muscarine
      levels. ABSTRACT: Action potential (AP) firing in mouse chromaffin cells (MCCs)
      is mainly sustained by Cav1.3 L-type channels that drive BK and SK currents and
      regulate the pacemaking cycle. As secretory units, CCs optimally recruit Ca(2+)
      channels when stimulated, a process potentially dependent on the modulation of
      the AP waveform. Our previous work has shown that a critical determinant of AP
      shape is voltage-gated sodium channel (Nav) channel availability. Here, we
      studied the contribution of Nav channels to firing patterns and AP shapes at rest
      (-50 mV) and upon stimulation (-40 mV). Using quantitative RT-PCR and
      immunoblotting, we show that MCCs mainly express tetrodotoxin (TTX)-sensitive,
      fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no Na(+)
      current during slow ramp depolarizations. Time constants and the percentage of
      recovery from fast inactivation and slow entry into closed-state inactivation are
      similar to that of brain Nav1.3 and Nav1.7 channels. The fraction of available
      Nav channels is reduced by half after 10 mV depolarization from -50 to -40 mV.
      This leads to low amplitude spikes and a reduction in repolarizing K(+) currents
      inverting the net current from outward to inward during the after
      hyperpolarization. When Nav channel availability is reduced by up to 20% of
      total, either by TTX block or steady depolarization, a switch from tonic to burst
      firing is observed. The spontaneous occurrence of high frequency bursts is rare
      under control conditions (14% of cells) but leads to major Ca(2+)-entry and
      increased catecholamine release. Thus, Nav1.3/Nav1.7 channel availability sets
      the AP shape, burst-firing initiation and regulates catecholamine secretion in
      MCCs. Nav channel inactivation becomes important during periods of high activity,
      mimicking stress responses.

PMID- 25620607
TI  - Immediate effects of electrical stimulation, diathermy, and physical exercise on
      lower limb arterial blood flow in diabetic women with peripheral arterial
      disease: a randomized crossover trial.
AB  - OBJECTIVE: The purpose of this study was to assess the effects of high-voltage
      electrical stimulation (HVES), continuous short wave diathermy, and physical
      exercise on arterial blood flow in the lower limbs of diabetic women with
      peripheral arterial disease. METHODS: A crossover study was carried out involving
      15 diabetic women (mean age of 77.87 +/- 6.20 years) with a diagnosis of
      peripheral arterial disease. One session of each therapeutic resource was held,
      with a 7-day washout period between protocols. Blood flow velocity was evaluated
      before each session and 0, 20, 40 and 60 minutes after the administration of each
      protocol. Two-way repeated-measures analysis of variance with Bonferroni post hoc
      test was used for the intragroup and intergroup comparisons. RESULTS: In the
      intragroup analysis, a significant reduction (P < .05) was found in blood flow
      velocity in the femoral and popliteal arteries over time with HVES and physical
      exercise and in the posterior tibial artery with the physical exercise protocol.
      However, no significant differences were found in the intergroup analysis (P >
      .05). CONCLUSION: Proximal blood circulation in the lower limb of diabetic women
      with peripheral arterial disease was increased by a single session of HVES and
      physical exercise, whereas distal circulation was only increased with physical
      exercise.

PMID- 25620608
TI  - Clinical outcomes for neurogenic claudication using a multimodal program for
      lumbar spinal stenosis: a retrospective study.
AB  - OBJECTIVE: The purpose of this preliminary study was to assess the effectiveness
      of a 6-week, nonsurgical, multimodal program that addresses the multifaceted
      aspects of neurogenic claudication. METHODS: In this retrospective study, 2
      researchers independently extracted data from the medical records from January
      2010 to April 2013 of consecutive eligible patients who had completed the 6-week
      Boot Camp Program. The program consisted of manual therapy twice per week (eg,
      soft tissue and neural mobilization, chiropractic spinal manipulation, lumbar
      flexion-distraction, and muscle stretching), structured home-based exercises, and
      instruction of self-management strategies. A paired t test was used to compare
      differences in outcomes from baseline to 6-week follow-up. Outcomes included self
      reported pain, disability, walking ability, and treatment satisfaction. RESULTS:
      A total of 49 patients were enrolled, with a mean age of 70 years. The mean
      difference in the Oswestry Disability Index was 15.2 (95% confidence interval
      [CI], 11.39-18.92), and that for the functional and symptoms scales of the Swiss
      Spinal Stenosis Questionnaire was 0.41 (95% CI, 0.26-0.56) and 0.74 (95% CI, 0.55
      0.93), respectively. Numeric pain scores for both leg and back showed
      statistically significant improvements. Improvements in all outcomes were
      clinically important. CONCLUSIONS: This study showed preliminary evidence for
      improved outcomes in patients with neurogenic claudication participating in a 6
      week nonsurgical multimodal Boot Camp Program.

PMID- 25620609
TI  - Biomechanical and histological effects of augmented soft tissue mobilization
      therapy on achilles tendinopathy in a rabbit model.
AB  - OBJECTIVE: Augmented soft tissue mobilization (ASTM) has been used to treat
      Achilles tendinopathy and is thought to promote collagen fiber realignment and
      hasten tendon regeneration. The objective of this study was to evaluate the
      biomechanical and histological effects of ASTM therapy on rabbit Achilles tendons
      after enzymatically induced injury. METHODS: This study was a non-human bench
      controlled research study using a rabbit model. Both Achilles tendons of 12
      rabbits were injected with collagenase to produce tendon injury simulating
      Achilles tendinopathy. One side was then randomly allocated to receive ASTM,
      while the other received no treatment (control). ASTM was performed on the
      Achilles tendon on postoperative days 21, 24, 28, 31, 35, and 38. Tendons were
      harvested 10 days after treatment and examined with dynamic viscoelasticity and
      light microscopy. RESULTS: Cross-sectional area in the treated tendons was
      significantly greater than in controls. Storage modulus tended to be lower in the
      treated tendons but elasticity was not significantly increased. Loss modulus was
      significantly lower in the treated tendons. There was no significant difference
      found in tangent delta (loss modulus/storage modulus). Microscopy of control
      tendons showed that the tendon fibers were wavy and type III collagen was well
      stained. The tendon fibers of the augmented soft tissue mobilization treated
      tendons were not wavy and type III collagen was not prevalent. CONCLUSION:
      Biomechanical and histological findings showed that the Achilles tendons treated
      with ASTM had better recovery of biomechanical function than did control tendons.

PMID- 25620610
TI  - Distal radius fractures result in alterations in scapular kinematics: a three
      dimensional motion analysis.
AB  - BACKGROUND: Scapular motion is closely integrated with arm motion. Injury to a
      distal segment requires compensatory changes in the proximal segments leading to
      alterations in scapular motion. Since the effects of distal injuries on scapular
      kinematics remain unknown, in the present study we investigated the influences on
      scapular motion in patients with distal injuries. METHODS: Sixteen subjects with
      a history of distal radius fracture and 20 asymptomatic healthy subjects
      (controls) participated in the study. Three-dimensional scapular and humeral
      kinematic data were collected on all 3 planes of shoulder elevation: frontal,
      sagittal, and scapular. All testing was performed in a single session; therefore,
      the sensors remained attached to the participants for all testing. The position
      and orientation data of the scapula at 30 degrees , 60 degrees , 90 degrees , and
      120 degrees  humerothoracic elevation and 120 degrees , 90 degrees , 60 degrees ,
      and 30 degrees  lowering were used for statistical comparisons. Independent
      samples t-test was used to compare the scapular internal/external rotation,
      upward/downward rotation, and anterior/posterior tilt between the affected side
      of subjects with a distal radius fracture and the dominant side of asymptomatic
      subjects at the same stage of humerothoracic elevation. FINDINGS: Scapular
      internal rotation was significantly increased at 30 degrees  elevation (P=0.01),
      90 degrees  elevation (P=0.03), and 30 degrees  lowering (P=0.03), and upward
      rotation was increased at 30 degrees  and 60 degrees  elevation (P<0.001) on the
      affected side during frontal plane elevation. Scapular upward rotation and
      anterior tilt were significantly increased during 30 degrees  lowering on both
      the scapular (P=0.002 and 0.02, respectively) and sagittal planes (P=0.01 and
      0.02. respectively). INTERPRETATION: Patients with distal radius fractures
      exhibit altered scapular kinematics, which may further contribute to the
      development of secondary musculoskeletal pathologies.

PMID- 25620611
TI  - Influence of chronic back pain on kinematic reactions to unpredictable arm pulls.
AB  - BACKGROUND: There is evidence that muscle reflexes are delayed in patients with
      chronic low back pain in response to perturbations. It is still unrevealed
      whether these delays accompanied by an altered kinematic or compensated by
      adaption of other muscle parameters. The aim of this study was to investigate
      whether chronic low back pain patients show an altered kinematic reaction and if
      such data are reliable for the classification of chronic low back pain. METHOD:
      In an experiment involving 30 females, sudden lateral perturbations were applied
      to the arm of a subject in an upright, standing position. Kinematics was used to
      distinguish between chronic low back pain patients and healthy controls.
      FINDINGS: A calculated model of a stepwise discriminant function analysis
      correctly predicted 100% of patients and 80% of healthy controls. The estimation
      of the classification error revealed a constant rate for the classification of
      the healthy controls and a slightly decreased rate for the patients.
      INTERPRETATION: Observed reflex delays and identified kinematic differences
      inside and outside the region of pain during impaired movement indicated that
      chronic low back pain patients have an altered motor control that is not
      restricted to the lumbo-pelvic region. This applied paradigm of external
      perturbations can be used to detect chronic low back pain patients and also
      persons without chronic low back pain but with an altered motor control. Further
      investigations are essential to reveal whether healthy persons with changes in
      motor function have an increased potential to develop chronic back pain.

PMID- 25620613
TI  - Response to: Do initial tidal volumes impact acute respiratory distress syndrome
      development in patients intubated in the emergency department?

PMID- 25620612
TI  - Quadrimodal distribution of death after trauma suggests that critical injury is a
      potentially terminal disease.
AB  - BACKGROUND: Patterns of death after trauma are changing due to advances in
      critical care. We examined mortality in critically injured patients who survived
      index hospitalization. METHODS: Retrospective analysis of adults admitted to a
      Level-1 trauma center (1/1/2000-12/31/2010) with critical injury was conducted
      comparing patient characteristics, injury, and resource utilization between those
      who died during follow-up and survivors. RESULTS: Of 1,695 critically injured
      patients, 1,135 (67.0%) were discharged alive. As of 5/1/2012, 977/1,135 (86.0%)
      remained alive; 75/158 (47.5%) patients who died during follow-up, died in the
      first year. Patients who died had longer hospital stays (24 vs. 17 days) and ICU
      LOS (17 vs. 8 days), were more likely to undergo tracheostomies (36% vs. 16%) and
      gastrostomies (39% vs. 16%) and to be discharged to rehabilitation (76% vs. 63%)
      or skilled nursing (13% vs. 5.8%) facilities than survivors. In multivariable
      models, male sex, older age, and longer ICU LOS predicted mortality. Patients
      with ICU LOS >16 days had 1.66 odds of 1-year mortality vs. those with shorter
      ICU stays. CONCLUSIONS: ICU LOS during index hospitalization is associated with
      post-discharge mortality. Patients with prolonged ICU stays after surviving
      critical injury may benefit from detailed discussions about goals of care after
      discharge.

PMID- 25620614
TI  - Evaluation of urinary microRNA panel in bladder cancer diagnosis: relation to
      bilharziasis.
AB  - We assessed the differential expression of a urinary panel of microRNAs (miRs) in
      terms of potential application as diagnostic markers of bladder cancer (BC) and
      relationship to bilharziasis. We investigated voided urine samples and blood from
      patients with BC (n = 188), benign bladder lesions (n = 88), and age-matched
      controls (n = 92). Five miRs (miR-210, miR-10b, miR-29c, miR-221, and miR-23a)
      were selected from previous microarray signature profiling (released by
      miR2Disease). Afterward, they were validated using polymerase chain reaction
      array. The expression levels of miR-210, miR-10b, and miR-29c in the urine
      samples were significantly higher in BC (P < 0.001). The receiver-operating
      characteristic curve analyses demonstrated that each miR had good sensitivity and
      specificity for distinguishing patients with BC from patients without BC (miR
      210, 71.3% and 91.1%; miR-10b, 80.9% and 91.1%; and miR-183, 71.3% and 88.9%). On
      combining the 3 miR detection data with the urinary cytology, the results
      sensitivity increased to 95.2%. Relative quantity mean rank of the miR-29c was
      significantly higher in the bilharzial-positive patients compared with bilharzial
      negative patients. To conclude, urine miR-210, miR-10b, and miR-29c are promising
      tumor markers for BC: bilharzial and nonbilharzial. 

PMID- 25620615
TI  - CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers.
AB  - More than 25% of the patients with breast cancer (BC) develop metastatic disease.
      In the present study, we investigated the relationship between DNA methylation
      levels in genes regulating cell growth, invasiveness, and metastasis and advanced
      BCs and evaluated the clinical utility of methylation profiles for detecting
      metastatic potential. Pyrosequencing was used to quantify methylation levels in
      11 cancer-associated genes in primary tumors (PTs), lymph node metastases (LNMs),
      plasma (PL), and blood cells from 206 patients with invasive BC. Protein
      expression was evaluated using immunohistochemistry. PTs showed hypermethylation
      of A isoform of the RAS-association domain family 1 (RASSF1A), adenomatous
      polyposis coli (APC), chemokine C-X-C motif ligand 12 (CXCL12), and disintegrin
      and metalloprotease domain 23 (ADAM23) (means 38.98%, 24.84%, 12.04%, and 10.01%,
      respectively). Positive correlations were identified between methylations in PTs
      and LNMs, but not between PL and PTs. The cumulative methylation of PTs and LNMs
      manifested similar spectrums of methylated genes that indicate the maintaining of
      aberrant methylation during breast tumorigenesis. Significantly increased
      methylation levels in RASSF1A, APC, CXCL12, and ADAM23 were found in estrogen
      receptor (ER) positive BCs in comparison with ER negative cases. Regarding these
      results, the evaluation of DNA methylation could be more informative in testing
      of patients with ER positive BC. The risk for LNMs development and higher
      proliferation of cancer cells measured through Ki-67 expression was increased by
      hypermethylation of CXCL12 and ADAM23, respectively. Therefore, the
      quantification of CXCL12 and ADAM23 methylation could be useful for the
      prediction of advanced stage of BC. 

PMID- 25620616
TI  - Comparing methods for determining motor-hand lateralization based on fTCD
      signals.
AB  - The lateralization index (LI) as determined from functional transcranial Doppler
      sonography (fTCD) can be used to determine the hemispheric organization of neural
      activation during a behavioral task. Previous studies have proposed different
      methods to determine this index, but to our knowledge no studies have compared
      the performance of these methods. In this study, we compare two established
      methods with a simpler method proposed here. The aim was to see whether similar
      results could be achieved with a simpler method and to give an indication of the
      analysis steps required to determine the LI. A simple unimanual motor task was
      performed while fTCD was acquired, and the LI determined by each of these methods
      was compared. In addition, LI determined by each method was related to
      behavioural output in the form of degree of handedness. The results suggest that
      although the methods differed in complexity, they yielded similar results when
      determining the lateralization of motor functions, and its correlation with
      behavior. Further investigation is needed to expand the conclusions of this
      preliminary study, however the new method proposed in the paper has great
      potential as it is much simpler than the more established methods yet yields
      similar results. 

PMID- 25620617
TI  - Post-growth purification of Co nanostructures prepared by focused electron beam
      induced deposition.
AB  - In the majority of cases nanostructures prepared by focused electron beam induced
      deposition (FEBID) employing an organometallic precursor contain predominantly
      carbon-based ligand dissociation products. This is unfortunate with regard to
      using this high-resolution direct-write approach for the preparation of
      nanostructures for various fields, such as mesoscopic physics, micromagnetism,
      electronic correlations, spin-dependent transport and numerous applications. Here
      we present an in situ cleaning approach to obtain pure Co-FEBID nanostructures.
      The purification procedure lies in the exposure of heated samples to a H2
      atmosphere in conjunction with the irradiation by low-energy electrons. The key
      finding is that the combination of annealing at 300  degrees C, H2 exposure and
      electron irradiation leads to compact, carbon- and oxygen free Co layers down to
      a thickness of about 20 nm starting from as-deposited Co-FEBID structures. In
      addition to this, in temperature-dependent electrical resistance measurements on
      post-processed samples we find a typical metallic behavior. In low-temperature
      magnetoresistance and Hall effect measurements we observe ferromagnetic behavior.

PMID- 25620618
TI  - Regulation of nutrition-associated receptors in blood monocytes of normal weight
      and obese humans.
AB  - Obesity, type 2 diabetes and associated metabolic diseases are characterized by
      low-grade systemic inflammation which involves interplay of nutrition and
      monocyte/macrophage functions. We suggested that some factors such as nutrient
      components, neuropeptides involved in the control of gastrointestinal functions,
      and gastrointestinal hormones might influence immune cell functions and in this
      way contribute to the disease pathogenesis. The aim of this study was to
      investigate the mRNA expression of twelve nutrition-associated receptors in
      peripheral blood mononuclear cells (PBMC), isolated monocytes and monocyte
      derived macrophages and their regulation under the switching from the high
      carbohydrate low-fat diet to the low-carbohydrate high-fat (LC/HFD) isocaloric
      diet in healthy humans. The mRNA expression of receptors for short chain fatty
      acids (GPR41, GPR43), bile acids (TGR5), incretins (GIPR, GLP1R), cholecystokinin
      (CCKAR), neuropeptides VIP and PACAP (VIPR1, VIPR2), and neurotensin (NTSR1) was
      detected in PBMC and monocytes, while GPR41, GPR43, GIPR, TGR5, and VIPR1 were
      found in macrophages. Correlations of the receptor expression in monocytes with a
      range of metabolic and inflammatory markers were found. In non-obese subjects,
      the dietary switch to LC/HFD induced the increase of GPR43 and VIPR1 expression
      in monocytes. No significant differences of receptor expression between normal
      weight and moderately obese subjects were found. Our study characterized for the
      first time the expression pattern of nutrition-associated receptors in human
      blood monocytes and its dietary-induced changes linking metabolic responses to
      nutrition with immune functions in health and metabolic diseases. 

PMID- 25620619
TI  - Disease Control in Wildlife: Evaluating a Test and Cull Programme for Bovine
      Tuberculosis in African Buffalo.
AB  - Providing an evidence base for wildlife population management is difficult, due
      to limited opportunities for experimentation and study replication at the
      population level. We utilized an opportunity to assess the outcome of a test and
      cull programme aimed at limiting the spread of Mycobacterium bovis in African
      buffalo. Buffalo act as reservoirs of M. bovis, the causative agent of bovine
      tuberculosis (BTB), which can have major economic, ecological and public health
      impacts through the risk of infection to other wildlife species, livestock and
      surrounding communities. BTB prevalence data were collected in conjunction with
      disease control operations in Hluhluwe-iMfolozi Park, South Africa, from 1999 to
      2006. A total of 4733 buffalo (250-950 per year) were tested for BTB using the
      single comparative intradermal tuberculin (SCIT) test, with BTB-positive animals
      culled, and negative animals released. BTB prevalence was spatially and
      temporally variable, ranging from 2.3% to 54.7%. Geographic area was a strong
      predictor of BTB transmission in HiP, owing to relatively stable herds and home
      ranges. Herds experiencing more intensive and frequent captures showed reduced
      per capita disease transmission risk and less increase in herd prevalence over
      time. Disease hot spots did not expand spatially over time, and BTB prevalence in
      all but the hot spot areas was maintained between 10% and 15% throughout the
      study period. Our data suggest that HiP's test and cull programme was effective
      at reducing BTB transmission in buffalo, with capture effort and interval found
      to be the crucial components of the programme. The programme was thus successful
      with respect to the original goals; however, there are additional factors that
      should be considered in future cost/benefit analyses and decision-making. These
      findings may be utilized and expanded in future collaborative work between
      wildlife managers, veterinarians and scientists, to optimize wildlife disease
      control programmes and mitigate conflict at the interface of conservation,
      agricultural and urban areas.

PMID- 25620620
TI  - Untangling interactions of a zinc(II) complex containing a coumarin-porphyrin
      unit with alkaloids in water solutions: a photophysical study.
AB  - A metal complex 1 derivative from a coumarin bearing a porphyrin unit was
      spectroscopically characterized and its sensing ability towards the alkaloids
      caffeine 2, nicotine 3 and cotinine 4 was evaluated in these studies. This probe
      shows to be sensitive to the alkaloids studied, where a detectable amount of 2.5
      +/- 0.3 MUM of cotinine was determined in dam water from the Vigia Dam located in
      the Montoito village region, Alentejo district, Portugal. The interaction of 1
      with cotinine was also verified by MALDI-TOF-MS, where it was found with peaks at
      877.2 and 1053.3 m/z corresponding to the species [1H](+) and [1CotinineH](+),
      respectively.

PMID- 25620621
TI  - Excitation of surface plasmons from silver nanowires embedded in polymer
      nanofibers.
AB  - We report an excitation of surface plasmons in silver nanowires (AgNWs) which
      were embedded in flexible polymer nanofibers. Using waveguiding excitation,
      surface plasmons in AgNWs were excited and propagated. By directing light of 650,
      532, and 473 nm wavelengths into the nanofiber, surface plasmons in an embedded
      single AgNW (average diameter 400 nm, length 4.3 MUm) were excited and the
      corresponding propagation lengths for the three wavelengths are 10.6, 7.7, and
      5.1 MUm. It was also found that, when a spatially incoherent white light of a
      halogen lamp with an excitation optical power of 80 MUW was coupled into the
      polymer nanofiber, a surface plasmon mediated interference fringe was observed.
      In addition, on the basis of surface plasmon excitation, two adjacent AgNWs
      embedded in the polymer nanofibers were demonstrated to serve as coupled
      plasmonic waveguides. 

PMID- 25620622
TI  - Melanogenic actinomycetes from rhizosphere soil-antagonistic activity against
      Xanthomonas oryzae and plant-growth-promoting traits.
AB  - A total of 210 melanogenic actinomycetes were isolated from 75 rhizospheric soils
      using ISP6 and ISP7 agar supplemented with antifungal and antibacterial agents.
      Their morphological characteristics and the presence of ll-diaminopimelic acid in
      whole-cell hydrolyzates revealed that all isolates belonged to the genus
      Streptomyces. Their ability to inhibit the growth of 2 pathogenic rice bacteria,
      Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, was observed
      using the agar overlay method. The results indicated that 61.9% of the isolates
      could inhibit at least one of the tested rice pathogens. Among these, isolate
      TY68-3 showed the highest antibacterial activity and siderophore production. The
      16S rRNA gene sequence analysis of 46 representative isolates revealed that
      isolates with high similarity to Streptomyces bungoensis were frequently found.
      The present study indicated the potential of melanogenic actinomycetes for use as
      biocontrol agents against X. oryzae as well as their diversity in rhizospheric
      soils. 

PMID- 25620623
TI  - Paul von Rague Schleyer (1930-2014).
AB  - Paul von Rague Schleyer, Graham Perdue Professor at the University of Georgia
      passed away on November 21, 2014. Schleyer was an eminent and prolific physical
      organic chemist, whose pioneering contributions included the application of
      computational chemistry to broad fields of physical organic, inorganic,
      organometallic, and mechanistic chemistry concepts. 

PMID- 25620625
TI  - Phosphorylation and turnover of paxillin in focal contacts is controlled by force
      and defines the dynamic state of the adhesion site.
AB  - Micro-environmental clues are critical to cell behavior. One of the key elements
      of migration is the generation and response to forces. Up to now there is no
      definitive concept on how the generation and responses to cellular forces
      influence cell behavior. Here, we show that phosphorylation of paxillin is a
      crucial event in the response to exogenous forces. Application of force induced
      growth of adhesion sites and this phenomenon was accompanied by a downregulation
      of Src family kinase activity, which in turn led to a decrease in the
      phosphorylation of paxillin at the tyrosine residues Y31 and Y118. The force
      dependent growth of adhesion sites is mediated by a decrease in the turnover-rate
      of paxillin in focal contacts. This turnover critically depended on the
      phosphorylation state of paxillin at Y31/118. Paxillin is an important regulator
      in the control of the aggregate state of the whole adhesion site since the
      turnover of other adhesion site proteins such as vinculin is influenced by the
      phosphorylation state of paxillin as well. Taken together these data suggest that
      SFK dependent phosphorylation of paxillin is a crucial event in the regulation of
      adhesion site function in response to force.

PMID- 25620624
TI  - Reproducibility of MR-based liver fat quantification across field strength: Same
      day comparison between 1.5T and 3T in obese subjects.
AB  - PURPOSE: To examine the reproducibility of quantitative magnetic resonance (MR)
      methods to estimate hepatic proton density fat-fraction (PDFF) at different
      magnetic field strengths. MATERIALS AND METHODS: This Health Insurance
      Portability and Accountability Act (HIPAA)-compliant study was approved by the
      Institutional Review Board. Following informed consent, 25 severely obese
      subjects (mean body mass index [BMI]: 45 +/- 4, range: 38-53 kg/m(2) ) were
      scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho
      chemical shift-encoded gradient-echo-based imaging methods were acquired to
      estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude
      based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right
      liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were
      made between methods (MRI-C, MRI-M, MRS) at each field strength and for each
      method across field strengths. RESULTS: 1.5T vs. 3T regression analyses for MRI
      C, MRI-M, and MRS PDFF measurements yielded R(2) values of 0.99, 0.97, and 0.90,
      respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0),
      indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b =
      1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = -1.4 [-2.4, -0.5]); MRS (m =
      0.98 [0.82, 1.15], b = 1.2 [-0.2, 3.0]). Comparing MRI-C and MRI-M yielded an
      R(2)  = 0.98 (m = 1.1 [1.02, 1.16], b = -1.8 [-2.8, -1.1]) at 1.5T, and R(2)  =
      0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. CONCLUSION: This study
      demonstrates that PDFF estimation is reproducible across field strengths and
      across two confounder-corrected MR-based methods.

PMID- 25620626
TI  - AhR expression and polymorphisms are associated with risk of coronary arterial
      disease in Chinese population.
AB  - The aryl hydrocarbon receptor (AhR) mediates the control of environmental
      toxicity, and modulates the development and pathogenesis of the cardiovascular
      system. However, little is known about the role of AhR in coronary arterial
      disease (CAD) susceptibility. We therefore conducted a case-control study in a
      Chinese population, and assessed the potential association between AhR variants
      and CAD susceptibility. Compared with the controls, circulating AhR expression
      was found to be significantly increased in patients with CAD and its subtypes
      including ST-segment and non-ST-segment elevation myocardial infarction, and
      stable and unstable angina pectoris. Receiver operating characteristic (ROC)
      analysis to evaluate the effect of AhR on CAD progression showed it to be a
      potent biomarker for CAD. Genotype frequencies of AhR rs2066853 differed
      significantly between CAD and control subjects, while smoking and hyperlipidemia
      markedly promoted CAD risk relative to the AhR polymorphism. Moreover, a
      significant difference in AhR variant distribution was observed between the four
      CAD subtypes with different severities. The expression level and functional
      polymorphisms of circulating AhR may affect the susceptibility and progression of
      CAD in Chinese populations. This provides a novel view of the etiology and
      epidemiology of CAD, and will contribute to the diagnosis and therapy of this
      severe disease. 

PMID- 25620627
TI  - Optimizing the order of hypotheses in serial testing of multiple endpoints in
      clinical trials.
AB  - Clinical trials usually collect information on a large number of variables or
      endpoints, including one or more primary endpoints as well as a number of
      secondary endpoints representing different aspects of treatment effectiveness and
      safety. In this article, we focus on serial testing procedures that test multiple
      endpoints in a pre-specified order, and consider how to optimize the order of
      endpoints subject to any clinical constraints, with respect to the expected
      number of successes (i.e., endpoints that reach statistical significance) or the
      expected gain (if endpoints are associated with numerical utilities). We consider
      some common approaches to this problem and propose two new approaches: a greedy
      algorithm based on conditional power and a simulated annealing algorithm that
      attempts to improve a given sequence in a random and iterative fashion.
      Simulation results indicate that the proposed algorithms are useful for finding a
      high-performing sequence, and that optimized fixed sequence procedures can be
      competitive against traditional multiple testing procedures such as Holm's. The
      methods and findings are illustrated with two examples concerning migraine and
      asthma.

PMID- 25620628
TI  - Side-chain interactions in the regulatory domain of human glutamate dehydrogenase
      determine basal activity and regulation.
AB  - Glutamate Dehydrogenase (GDH) is central to the metabolism of glutamate, a major
      excitatory transmitter in mammalian central nervous system (CNS). hGDH1 is
      activated by ADP and L-leucine and powerfully inhibited by GTP. Besides this
      housekeeping hGDH1, duplication led to an hGDH2 isoform that is expressed in the
      human brain dissociating its function from GTP control. The novel enzyme has
      reduced basal activity (4-6% of capacity) while remaining remarkably responsive
      to ADP/L-leucine activation. While the molecular basis of this evolutionary
      adaptation remains unclear, substitution of Ser for Arg443 in hGDH1 is shown to
      diminish basal activity (< 2% of capacity) and abrogate L-leucine activation. To
      explore whether the Arg443Ser mutation disrupts hydrogen bonding between Arg443
      and Ser409 of adjacent monomers in the regulatory domain ('antenna'), we replaced
      Ser409 by Arg or Asp in hGDH1. The Ser409Arg-1 change essentially replicated the
      Arg443Ser-1 mutation effects. Molecular dynamics simulation predicted that Ser409
      and Arg443 of neighboring monomers come in close proximity in the open
      conformation and that introduction of Ser443-1 or Arg409-1 causes them to
      separate with the swap mutation (Arg409/Ser443) reinstating their proximity. A
      swapped Ser409Arg/Arg443Ser-1 mutant protein, obtained in recombinant form,
      regained most of the wild-type hGDH1 properties. Also, when Ser443 was replaced
      by Arg443 in hGDH2 (as occurs in hGDH1), the Ser443Arg-2 mutant acquired most of
      the hGDH1 properties. Hence, side-chain interactions between 409 and 443
      positions in the 'antenna' region of hGDHs are crucial for basal catalytic
      activity, allosteric regulation, and relative resistance to thermal inactivation.

PMID- 25620629
TI  - Efficacy and safety of long-term inhaled antibiotic for patients with noncystic
      fibrosis bronchiectasis: a meta-analysis.
AB  - BACKGROUND AND AIMS: The evidence supported the use of nebulized antibiotics in
      non-cystic fibrosis (non-CF) bronchiectasis is indefinite. A meta-analysis was
      performed to determine the efficacy and safety of long-term inhaled antibiotics
      for patients with non-CF bronchiectasis. METHODS: PubMed, Embase, Web of Science
      and Cochrane Library databases were searched up to March 20, 2014. Reduction of
      sputum bacterial density, eradication of sputum Pseudomonas aeruginosa, the risk
      of exacerbations and other clinical outcomes related to inhalation treatment were
      analyzed. RESULTS: Three hundred seventy articles were searched. Eight randomized
      controlled trials recruiting 539 patients were included in this meta-analysis.
      Long-term inhaled antibiotics showed an obvious reduction of the sputum bacterial
      density [weighted mean difference = 2.85, 95% confidence interval (CI): 1.6-4.09,
      P < 0.00001] and augment eradication of sputum P. aeruginosa [odds ratio (OR) =
      6.6, 95% CI: 2.93-14.86, P < 0.00001]. No evidences showed higher risk of P.
      aeruginosa resistance after inhaled therapy. In addition, nebulized therapy
      reduced the amount of patients with exacerbation (OR = 0.46, 95% CI: 0.21-1.00, P
      = 0.05). However, patients with inhaled antibiotics were more likely to suffer
      wheeze (OR = 6.74, 95% CI: 2.22-20.52, P = 0.0008) and bronchospasm (OR = 2.84,
      95% CI: 1.11-7.25, P = 0.03). CONCLUSION: For patients with non-CF
      bronchiectasis, long-term inhaled antibiotics can effectively reduce the sputum
      bacterial density, increase P.A eradication and attenuate the risk of
      exacerbation, however, accompanied with higher risk of wheeze and bronchospasm.

PMID- 25620631
TI  - Stress and salt sensitivity in primary hypertension.
AB  - As the development of hypertension and target organ damage becomes more
      prevalent, it becomes exceedingly important to determine the underlying
      mechanisms through which this detrimental development occurs. Specifically, our
      studies and others have explored mechanisms through which stress elicits a salt
      sensitive response in approximately 20-30 % of the population, resulting in the
      early development of hypertension and target organ damage. Data associated with
      this stress-induced cardiovascular response pattern have recently demonstrated
      additional effects across the body systems including factors contributing to the
      development of osteoporosis, obesity, autoimmune disease, and chronic
      inflammation. As each of these diseases become more prevalent in conjunction with
      hypertension, further research may discover stress and salt sensitivity to be at
      the "heart" of the matter for the development of many of today's most deadly
      conditions.

PMID- 25620632
TI  - The clinical relevance of the percentage flow-mediated dilation index.
AB  - In 2010, the American College of Cardiology Foundation and American Heart
      Association could not recommend brachial artery percentage flow-mediated dilation
      (FMD%) for risk assessment of coronary artery disease (CAD) in asymptomatic
      adults. We aimed to scrutinise past and recently published findings regarding
      FMD% in this same context of clinical utility and conclude that (1) the question
      of whether brachial FMD% is a suitable substitute for coronary vasodilation is
      addressed by method agreement statistics rather than the correlation coefficients
      that have been reported in past studies. Also, the much-repeated view that
      brachial FMD% and coronary vasodilation are "closely related" is not entirely
      justified, even before the influence of baseline lumen diameters on this
      relationship is accounted for; (2) along with the specialist training and the
      considerable time (>=1 h) that is required for the FMD% protocol, the error in
      individual measurements and population reference ranges is too large for clinical
      decisions to be robust on individual patients; (3) many interventions that are
      proposed to change FMD% also change baseline artery diameter, which can bias
      estimates of any intervention effects on the flow-mediated response per se, and
      (4) the FMD% index generates spurious correlations between shear rate, artery
      diameter and endothelial function, which may help to explain the apparent
      paradoxes of FMD% being higher in obese people and lower in athletes. In
      conclusion, the clinical relevance of brachial artery flow-mediated dilation is
      unclear at present. The dependence of the chosen index, FMD%, on initial artery
      size has contributed to this lack of clarity.

PMID- 25620630
TI  - Neuroprotective mechanisms of the ACE2-angiotensin-(1-7)-Mas axis in stroke.
AB  - The discovery of beneficial neuroprotective effects of the angiotensin converting
      enzyme 2-angiotensin-(1-7)-Mas axis [ACE2-Ang-(1-7)-Mas] in ischemic and
      hemorrhagic stroke has spurred interest in a more complete characterization of
      its mechanisms of action. Here, we summarize findings that describe the
      protective role of the ACE2-Ang-(1-7)-Mas axis in stroke, along with a focused
      discussion on the potential mechanisms of neuroprotective effects of Ang-(1-7) in
      stroke. The latter incorporates evidence describing the actions of Ang-(1-7) to
      counter the deleterious effects of angiotensin II (AngII) via its type 1
      receptor, including anti-inflammatory, anti-oxidant, vasodilatory, and angiogenic
      effects, and the role of altered kinase-phosphatase signaling. Interactions of
      Mas with other receptors, including bradykinin receptors and AngII type 2
      receptors are also considered. A more complete understanding of the mechanisms of
      action of Ang-(1-7) to elicit neuroprotection will serve as an essential step
      toward research into potential targeted therapeutics in the clinical setting. 

PMID- 25620633
TI  - Cardiovascular hypertensive emergencies.
AB  - Inevitably, a small proportion of patients with systematic hypertension will
      develop hypertensive crisis at some point. Hypertensive crises can be divided
      into hypertensive emergency or hypertensive urgency according to the presence or
      lack of acute target organ damage. In this review, we discuss cardiovascular
      hypertensive emergencies, including acute coronary syndrome, aortic dissection,
      congestive heart failure, and sympathomimetic hypertensive crises, including
      those caused by cocaine use. Each presents in a unique fashion, although some
      hypertensive emergency patients report nonspecific symptoms. Treatment includes
      several effective and rapid-acting medications to safely reduce the blood
      pressure, protect remaining end-organ function, relieve symptoms, minimize the
      risk of complications, and thereby improve patient outcomes. 

PMID- 25620634
TI  - Antihypertensive therapy and the J-curve: fact or fiction?
AB  - Hypertension is a major modifiable risk factor for cardiovascular morbidity and
      mortality. Despite more than five decades of hypertension treatment, there still
      exist both a lack of evidence and a clear consensus to answer a fundamental
      question: What is the optimal blood pressure target in patients with
      hypertension? Early epidemiologic studies suggested the notion of the lower the
      blood pressure, the better the outcomes; however, others have demonstrated a J
      curve phenomenon with worse outcomes at both low and very high blood pressures.
      Although the existence of such a J-curve remains a topic of debate, there is now
      increasing recognition of target organ heterogeneity wherein the optimal blood
      pressure depends on the target organ in question. For cardiac protection, the
      current body of evidence does not support a systolic blood pressure goal of lower
      than 130-140 mmHg. For cerebrovascular protection, however, lower blood pressure
      seems to be better with a sustained reduction in events down to a systolic blood
      pressure of 110-120 mmHg. The J-curve phenomenon is therefore both fact and
      fiction based on the target organ in question.

PMID- 25620636
TI  - Selective Efficacy of Temsirolimus on Bone Metastases in Chromophobe Renal Cell
      Carcinoma.

PMID- 25620637
TI  - Ultrasonography and C-reactive protein can predict the outcomes of voiding
      cystography after the first urinary tract infection.
AB  - AIM: This study evaluated whether sex, clinical variables, laboratory variables
      or ultrasonography predicted the presence of vesicoureteric reflux during the
      first episode of urinary tract infection in paediatric patients. We also aimed to
      define the criteria that indicated the need for voiding cystography testing.
      METHODS: We used voiding cystography to investigate 200 patients who experienced
      their first urinary tract infection at our institution between 2004 and 2013 and
      retrospectively analysed the data by reviewing their medical records. RESULTS:
      Sex (p = 0.001), peak blood C-reactive protein levels (p < 0.001), the duration
      of fever after antibiotic administration (p = 0.007) and the ultrasonography
      findings grade (p < 0.001) were significantly different between patients with and
      without vesicoureteric reflux. Grade IV-V ultrasonography findings and C-reactive
      protein levels of >=80 mg/L predicted vesicoureteric reflux with a sensitivity,
      specificity and odds ratio of 47.8%, 87.8% and 6.59 (95% confidence interval =
      3.26-13.33), respectively (p < 0.001). CONCLUSION: Voiding cystography should be
      performed for patients with C-reactive protein levels of >=80 mg/L and grade IV-V
      ultrasonography findings, but is not necessary in patients with C-reactive
      protein levels of <80 mg/L and grade I-III ultrasonography findings.

PMID- 25620638
TI  - Gender differences in muscle blood volume reduction in the tibialis anterior
      muscle during passive plantarflexion.
AB  - Physical flexibility, such as joint range of motion and muscle extension, may
      influence muscle blood volume. Women have been shown to have a greater degree of
      flexibility than men. We examined whether there is a gender difference in the
      relationship between fascicle length and muscle blood volume or oxygenation in
      untrained men and women. In 16 untrained men and thirteen untrained women, we
      measured the total-[haemoglobin (Hb) + myoglobin (Mb)] (total-[Hb + Mb]) and
      relative oxy-[Hb + Mb] after calibrating baseline and arterial occlusion
      deoxygenation levels with near-infrared spectroscopy. Also, fascicle length was
      measured with B-mode ultrasonography at the tibialis anterior muscle during
      passive plantarflexion. Increases in fascicle length from baseline (ankle joint
      angle 120 degrees , composed from the caput fibulae, the malleolus (pivot), and
      the distal epiphysis of the fifth metatarsal bone) were greater in women than in
      men during plantarflexion of 140 degrees  and 160 degrees  and the maximal angle
      without pain. However, the decreases in total-[Hb + Mb] and relative oxy-[Hb +
      Mb] from baseline were not different between women and men at any degree of
      plantarflexion. Moreover, fascicle length and total-[Hb + Mb]/muscle thickness
      (men > women) showed a similar relationship, with muscle thickness increasing
      capillary compression. These findings indicate the possibility of a mechanical
      function underlying muscle blood volume during muscle stretching, which is
      greater in women than in men. 

PMID- 25620635
TI  - The impacts of obesity on the cardiovascular and renal systems: cascade of events
      and therapeutic approaches.
AB  - There is a neglected epidemic of both obesity and metabolic syndrome in
      industrialized and unindustrialized countries all over the globe. Both conditions
      are associated with a high incidence of other serious pathologies, such as
      cardiovascular and renal diseases. In this article, we review the potential
      underlying mechanisms by which obesity and metabolic syndrome promote
      hypertension, including changes in cardiovascular-renal physiology induced by
      leptin, the sympathetic nervous system, the renin-angiotensin-aldosterone system,
      insulin resistance, free fatty acids, natriuretic peptides, and proinflammatory
      cytokines. We also discuss the potential underlying mechanisms by which obesity
      promotes other cardiovascular and renal conditions, as well as available
      nonpharmacologic and pharmacologic approaches for treating obesity-induced
      hypertension. The findings presented herein suggest that adipocytes may be a key
      regulator of cardiovascular and renal function.

PMID- 25620639
TI  - Hurricanes accelerated the Florida-Bahamas lionfish invasion.
AB  - In this study, we demonstrate how perturbations to the Florida Current caused by
      hurricanes are relevant to the spread of invasive lionfish from Florida to the
      Bahamas. Without such perturbations, this current represents a potential barrier
      to the transport of planktonic lionfish eggs and larvae across the Straits of
      Florida. We further show that once lionfish became established in the Bahamas,
      hurricanes significantly hastened their spread through the island chain. We gain
      these insights through: (1) an analysis of the direction and velocity of
      simulated ocean currents during the passage of hurricanes through the Florida
      Straits and (2) the development of a biophysical model that incorporates the
      tolerances of lionfish to ocean climate, their reproductive strategy, and
      duration that the larvae remain viable in the water column. On the basis of this
      work, we identify 23 occasions between the years 1992 and 2006 in which lionfish
      were provided the opportunity to breach the Florida Current. We also find that
      hurricanes during this period increased the rate of spread of lionfish through
      the Bahamas by more than 45% and magnified its population by at least 15%. Beyond
      invasive lionfish, we suggest that extreme weather events such as hurricanes
      likely help to homogenize the gene pool for all Caribbean marine species
      susceptible to transport. 

PMID- 25620640
TI  - Ascl2 acts as an R-spondin/Wnt-responsive switch to control stemness in
      intestinal crypts.
AB  - The Wnt signaling pathway controls stem cell identity in the intestinal
      epithelium and in many other adult organs. The transcription factor Ascl2 (a Wnt
      target gene) is a master regulator of intestinal stem cell identity. It is
      unclear how the continuous Wnt gradient along the crypt axis is translated into
      discrete expression of Ascl2 and discrete specification of stem cells at crypt
      bottoms. We show that (1) Ascl2 is regulated in a direct autoactivatory loop,
      leading to a distinct on/off expression pattern, and (2) Wnt/R-spondin can
      activate this regulatory loop. This mechanism interprets the Wnt levels in the
      intestinal crypt and translates the continuous Wnt signal into a discrete Ascl2
      "on" or "off" decision. In turn, Ascl2, together with beta-catenin/Tcf, activates
      the genes fundamental to the stem cell state. In this manner, Ascl2 forms a
      transcriptional switch that is both Wnt responsive and Wnt dependent to define
      stem cell identity. 

PMID- 25620641
TI  - ST2 marker might help to stratify in-hospital high risk patients with Tako-tsubo
      cardiomyopathy.

PMID- 25620642
TI  - Do persons with stroke benefit from statin-fibrate combination therapy?

PMID- 25620643
TI  - Less surgery improves survival for advanced colorectal cancer.

PMID- 25620644
TI  - Unmet needs of cancer survivors.

PMID- 25620645
TI  - Shrubs tracing sea surface temperature--Calluna vulgaris on the Faroe Islands.
AB  - The climate of Central and Northern Europe is highly influenced by the North
      Atlantic Ocean due to heat transfer from lower latitudes. Detailed knowledge
      about spatio-temporal variability of sea surface temperature (SST) in that region
      is thus of high interest for climate and environmental research. Because of the
      close relations between ocean and coastal climate and the climate sensitivity of
      plant growth, annual rings of woody plants in coastal regions might be used as a
      proxy for SST. We show here for the first time the proxy potential of the common
      and widespread evergreen dwarf shrub Calluna vulgaris (heather), using the Faroe
      Islands as our case study. Despite its small and irregular ring structure, the
      species seems suitable for dendroecological investigations. Ring width showed
      high and significant correlations with summer and winter air temperatures and
      SST. The C. vulgaris chronology from the Faroe Islands, placed directly within
      the North Atlantic Current, clearly reflects variations in summer SSTs over an
      area between Iceland and Scotland. Utilising shrubs like C. vulgaris as easy
      accessible and annually resolved proxies offers an interesting possibility for
      reconstruction of the coupled climate-ocean system at high latitudes. 

PMID- 25620646
TI  - Mycosis fungoides-like lesions in a patient with diffuse cutaneous
      sporotrichosis.
AB  - BACKGROUND: Sporotrichosis is a subacute or chronic mycosis acquired by traumatic
      inoculation or inhalation of fungal conidia. It is caused by the dimorphic fungus
      Sporothrix, which causes different clinical presentations, being the cutaneous
      and lymphocutaneous variants being the most frequent. The disseminated cutaneous
      form is a rare presentation occurring in a minority of cases in Mexico. CASE
      REPORT: We report an atypical case of disseminated sporotrichosis in an alcoholic
      and iatrogenically immunosuppressed patient, whose clinical lesions resembled
      tumoral-stage mycosis fungoides. Histological examination and culture revealed
      the presence of Sporothrix schenckii. CONCLUSIONS: The patient was treated with
      itraconazole 200mg per day for 4 months with clinical resolution. To the best of
      our knowledge, this is the first report of this type of clinical manifestation.

PMID- 25620647
TI  - Reprint of: B cells in chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) continues to be a common complication
      of allogeneic hematopoietic stem cell transplantation. Unlike acute graft-versus
      host disease, which is mediated almost entirely by donor T cells, the immune
      pathology of cGVHD is more complex and donor B cells have also been found to play
      an important role. Recent studies from several laboratories have enhanced our
      understanding of how donor B cells contribute to this clinical syndrome and this
      has led to new therapeutic opportunities. Here, Dr Sarantopoulos reviews some of
      the important mechanisms responsible for persistent B cell activation and loss of
      B cell tolerance in patients with cGVHD. Dr Blazar describes recent studies in
      preclinical models that have identified novel B cell-directed agents that may be
      effective for prevention or treatment of cGVHD. Some B cell-directed therapies
      have already been tested in patients with cGVHD and Dr Cutler reviews the results
      of these studies documenting the potential efficacy of this approach. Supported
      by mechanistic studies in patients and preclinical models, new B cell-directed
      therapies for cGVHD will now be evaluated in clinical trials. 

PMID- 25620648
TI  - Reprint of: Recent advances in cytomegalovirus: an update on pharmacologic and
      cellular therapies.
AB  - The 2015 Tandem American Society for Blood and Marrow Transplantation/Center for
      International Blood and Marrow Transplant Meetings provide an opportunity to
      review the current status and future perspectives on therapy for cytomegalovirus
      (CMV) infection in the setting of hematopoietic stem cell transplantation (HSCT).
      After many years during which we have seen few tangible advances in terms of new
      antiviral drugs, we are now experiencing an exciting period of late-stage drug
      development, characterized by a series of phase III trials incorporating a
      variety of novel agents. These trials have the potential to shift our current
      standard therapeutic strategies, which generally involve pre-emptive therapy
      based on sensitive molecular surveillance, towards the prophylactic approaches we
      see more generally with other herpes viruses such as herpes simplex and varicella
      zoster. This comes at a time when the promise of extensive preclinical research
      has been translated into encouraging clinical responses with several cellular
      immunotherapy strategies, which have also been moved towards definitive late
      stage clinical trials. How these approaches will be integrated with the new wave
      of antiviral drugs remains open to conjecture. Although most of the focus of
      these cellular immunotherapy studies has been on adaptive immunity, and in
      particular T cells, an increasing awareness of the possible role of other
      cellular subsets in controlling CMV infection has developed. In particular, the
      role of natural killer (NK) cells is being revisited, along with that of
      gammadelta T cells. Depletion of NK cells in mice results in higher titers of
      murine CMV in tissues and increased mortality, whereas NK cell deficiency in
      humans has been linked to severe CMV disease. We will review recent progress in
      these areas. 

PMID- 25620649
TI  - Reprint of: Allogeneic hematopoietic cell transplantation for acute myeloid
      leukemia.
AB  - Allogeneic stem cell transplantation is an increasingly important treatment
      option in the management of adult acute myeloid leukemia (AML). The major causes
      of treatment failure remain disease relapse and treatment toxicity. In this
      review, Dr Vyas presents an overview of important recent data defining molecular
      factors associated with treatment failure in AML. He also identifies the emerging
      importance of leukemia stem cell biology in determining both response to therapy
      and relapse risk in AML. Dr Appelbaum discusses advances in the design and
      delivery of both myeloablative and reduced-intensity conditioning regimens,
      highlighting novel strategies with the potential to improve outcome. Dr Craddock
      discusses the development of both novel conditioning regimens and post
      transplantation strategies aimed at reducing the risk of disease relapse. 

PMID- 25620650
TI  - Rates of complete diagnostic testing for patients with acute myeloid leukemia.
AB  - In addition to cytogenetics, additional molecular markers of prognosis have been
      identified and incorporated into the management of patients with acute myeloid
      leukemia (AML). We hypothesized that rates of molecular testing would be higher
      in an academic center versus community sites. A retrospective chart review
      included all de novo AML patients (excluding M3) at Kansas University Medical
      Center (KUMC) from January 2008 through April 2013. Records were evaluated for
      completeness of molecular testing as indicated by karyotype (FLT3, CEBPalpha,
      NPM1 in normal cytogenetics AML and c-KIT in core binding factor [CBF] AML). 271
      charts were reviewed: 98 with CN-AML and 29 with CBF AML. Seventy were diagnosed
      at KUMC, 57 at a community site. Molecular testing was sent in 76/98 (77%)
      patients with CN-AML. Patients diagnosed at KUMC had a significantly higher rate
      of molecular testing (51/55, 93%) as compared to those diagnosed at outside
      centers (18/43, 41%) (P < 0.001). Of 29 patients with CBF AML, c-kit mutational
      analysis was performed more frequently at KUMC (14/15, 93%) than in community
      sites (8/14, 57%) (P = 0.035). There was a trend towards increased testing at
      both KUMC and community sites in later years. Rates of molecular testing in AML
      were higher in an academic center versus community sites in the 5 years following
      the World Health Organization revised classification of AML. All physicians who
      diagnose and treat AML must remain up to date on the latest recommendations and
      controversies in molecular testing in order to appropriately risk stratify
      patients and determine optimal therapy.

PMID- 25620651
TI  - [Key aspects in interpreting clinical trials in radiology].
AB  - A clinical trial is an experimental study to evaluate the efficacy and safety of
      a treatment or diagnostic technique in human beings. To ensure the methodological
      quality of a clinical trial and the validity of its results, various checklists
      have been elaborated to identify biases that could invalidate its conclusions.
      This article focuses on the points we need to consider in the critical evaluation
      of a clinical trial. We can usually find this information in the "materials and
      methods" and "results" sections of articles. Randomization, follow-up (or
      analysis of losses), blinding, and equivalence between groups (apart from the
      intervention itself) are some key aspects related to design. In the "results"
      section, we need to consider what measures of clinical efficacy were used
      (relative risk, odds ratio, or number needed to treat, among others) and the
      precision of the results (confidence intervals). Once we have confirmed that the
      clinical trial fulfills these criteria, we need to determine whether the results
      can be applied in our environment and whether the benefits obtained justify the
      risks and costs involved. 

PMID- 25620652
TI  - Approaching the Hayflick limit.

PMID- 25620653
TI  - Progress for peripartum cardiomyopathy.

PMID- 25620654
TI  - Spectrophotometric and spectrofluorimetric determination of indacaterol maleate
      in pure form and pharmaceutical preparations: application to content uniformity.
AB  - Two simple, rapid, sensitive and precise spectrophotometric and
      spectrofluorimetric methods were developed for the determination of indacaterol
      maleate in bulk powder and capsules. Both methods were based on the direct
      measurement of the drug in methanol. In the spectrophotometric method (Method I)
      the absorbance was measured at 259 nm. The absorbance-concentration plot was
      rectilinear over the range 1.0-10.0 ug mL(-1) with a lower detection limit (LOD)
      of 0.078 ug mL(-1) and lower quantification limit (LOQ) of 0.238 ug mL(-1).
      Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence
      was measured at 358 nm after excitation at 258 nm. The fluorescence-concentration
      plot was rectilinear over the range of 1.0-40.0 ng mL(-1) with an LOD of 0.075 ng
      mL(-1) and an LOQ of 0.226 ng mL(-1). The proposed methods were successfully
      applied to the determination of indacaterol maleate in capsules with average
      percent recoveries +/- RSD% of 99.94 +/- 0.96 for Method I and 99.97 +/- 0.81 for
      Method II. In addition, the proposed methods were extended to a content
      uniformity test according to the United States Pharmacopoeia (USP) guidelines and
      were accurate, precise for the capsules studied with acceptance value 3.98 for
      Method I and 2.616 for Method II.

PMID- 25620655
TI  - Statin myalgia is not associated with reduced muscle strength, mass or protein
      turnover in older male volunteers, but is allied with a slowing of time to peak
      power output, insulin resistance and differential muscle mRNA expression.
AB  - Statins are associated with muscle myalgia and myopathy, which probably reduce
      habitual physical activity. This is particularly relevant to older people who are
      less active, sarcopaenic and at increased risk of statin myalgia. We hypothesised
      that statin myalgia would be allied to impaired strength and work capacity in
      older people, and determined whether differences aligned with divergences in lean
      mass, protein turnover, insulin sensitivity and the molecular regulation of these
      processes. Knee extensor strength and work output during 30 maximal isokinetic
      contractions were assessed in healthy male volunteers, nine with no statin use
      (control 70.4 +/- 0.7 years) and nine with statin myalgia (71.5 +/- 0.9 years).
      Whole body and leg glucose disposal, muscle myofibrillar protein synthesis (MPS)
      and leg protein breakdown (LPB) were measured during fasting (~5 mU l(-1)
      insulin) and fed (~40 mU l(-1) insulin + hyperaminoacidaemia) euglyceamic clamps.
      Muscle biopsies were taken before and after each clamp. Lean mass, MPS, LPB and
      strength were not different but work output during the initial three isokinetic
      contractions was 19% lower (P < 0.05) in statin myalgic subjects due to a delay
      in time to reach peak power output. Statin myalgic subjects had reduced whole
      body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity
      (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery
      rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis,
      increased at 1% FDR. Statin myalgia was associated with impaired muscle function,
      increased abdominal adiposity, whole body and leg insulin resistance, and
      evidence of mitochondrial dysfunction and apoptosis.

PMID- 25620656
TI  - Anxiety and depression are related to dyspnea and clinical control but not with
      thoracoabdominal mechanics in patients with COPD.
AB  - OBJECTIVE: To investigate the relationship between the presence of symptoms of
      anxiety or depression with breathing pattern and thoracoabdominal mechanics at
      rest and during exercise in COPD. METHODS: Cross-sectional study enrolled 54
      patients with COPD ranked according to Hospital Anxiety and Depression Scale
      (HAD) score and compared to dyspnea, clinical control, hypercapnia, breathing
      pattern and thoracoabdominal mechanics at rest and during exercise. RESULTS:
      Seventeen patients with COPD had no symptoms, 12 had anxiety symptoms, 13 had
      depressive symptoms and 12 had both symptoms. COPD with depressive symptoms
      presented greater degree of dyspnea (p<0.01). Poor clinical control was observed
      in COPD with anxious and/or depressive symptoms (p<0.05). Breathing pattern and
      thoracoabdominal mechanics were similar among all groups at rest and during
      exercise. CONCLUSIONS: COPD with symptoms of depression report more dyspnea.
      Anxiety and depression are associated with poor clinical control without impact
      on breathing pattern and thoracoabdominal mechanics in COPD.

PMID- 25620657
TI  - Autophagy-related prognostic signature for breast cancer.
AB  - Autophagy is a process that degrades intracellular constituents, such as long
      lived or damaged proteins and organelles, to buffer metabolic stress under
      starvation conditions. Deregulation of autophagy is involved in the progression
      of cancer. However, the predictive value of autophagy for breast cancer prognosis
      remains unclear. First, based on gene expression profiling, we found that
      autophagy genes were implicated in breast cancer. Then, using the Cox
      proportional hazard regression model, we detected autophagy prognostic signature
      for breast cancer in a training dataset. We identified a set of eight autophagy
      genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were
      significantly associated with overall survival in breast cancer. The eight
      autophagy genes were assigned as a autophagy-related prognostic signature for
      breast cancer. Based on the autophagy-related signature, the training dataset
      GSE21653 could be classified into high-risk and low-risk subgroups with
      significantly different survival times (HR = 2.72, 95% CI = (1.91, 3.87); P =
      1.37 * 10(-5)). Inactivation of autophagy was associated with shortened survival
      of breast cancer patients. The prognostic value of the autophagy-related
      signature was confirmed in the testing dataset GSE3494 (HR = 2.12, 95% CI =
      (1.48, 3.03); P = 1.65 * 10(-3)) and GSE7390 (HR = 1.76, 95% CI = (1.22, 2.54); P
      = 9.95 * 10(-4)). Further analysis revealed that the prognostic value of the
      autophagy signature was independent of known clinical prognostic factors,
      including age, tumor size, grade, estrogen receptor status, progesterone receptor
      status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we
      demonstrated that the autophagy signature could also predict distant metastasis
      free survival for breast cancer.

PMID- 25620658
TI  - Conserved residues of the Pro103-Arg115 loop are involved in triggering the
      allosteric response of the Escherichia coli ADP-glucose pyrophosphorylase.
AB  - The synthesis of glycogen in bacteria and starch in plants is allosterically
      controlled by the production of ADP-glucose by ADP-glucose pyrophosphorylase.
      Using computational studies, site-directed mutagenesis, and kinetic
      characterization, we found a critical region for transmitting the allosteric
      signal in the Escherichia coli ADP-glucose pyrophosphorylase. Molecular dynamics
      simulations and structural comparisons with other ADP-glucose pyrophosphorylases
      provided information to hypothesize that a Pro103-Arg115 loop is part of an
      activation path. It had strongly correlated movements with regions of the enzyme
      associated with regulation and ATP binding, and a network analysis showed that
      the optimal network pathways linking ATP and the activator binding Lys39 mainly
      involved residues of this loop. This hypothesis was biochemically tested by
      mutagenesis. We found that several alanine mutants of the Pro103-Arg115 loop had
      altered activation profiles for fructose-1,6-bisphosphate. Mutants P103A, Q106A,
      R107A, W113A, Y114A, and R115A had the most altered kinetic profiles, primarily
      characterized by a lack of response to fructose-1,6-bisphosphate. This loop is a
      distinct insertional element present only in allosterically regulated sugar
      nucleotide pyrophosphorylases that could have been acquired to build a triggering
      mechanism to link proto-allosteric and catalytic sites. 

PMID- 25620659
TI  - Brain oxidative damage restored by Sesbania grandiflora in cigarette smoke
      exposed rats.
AB  - Cigarette smoking has been associated with high risk of neurological diseases
      such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study
      was designed to evaluate the restorative effects of Sesbania grandiflora (S.
      grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain
      of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a
      period of 90 days and consecutively treated with S. grandiflora aqueous
      suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of
      3 weeks. The levels of protein carbonyl, nitric oxide, and activities of
      cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased,
      whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic
      acids, tissue protein and the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase and
      Mg(2+)-ATPase were significantly diminished in the brain of rats exposed to
      cigarette smoke as compared with control rats. Also cigarette smoke exposure
      resulted in a significant alteration in brain total lipid, total cholesterol,
      triglycerides and phospholipids content. Treatment of SGAS is regressed these
      alterations induced by cigarette smoke. The results of our study suggest that S.
      grandiflora restores the brain from cigarette smoke induced oxidative damage. S.
      grandiflora could have rendered protection to the brain by stabilizing their cell
      membranes and prevented the protein oxidation, probably through its free radical
      scavenging and anti-peroxidative effect. 

PMID- 25620660
TI  - Uptake and cellular distribution of nucleolar targeting peptides (NrTPs) in
      different cell types.
AB  - Nucleolar targeting peptides (NrTPs) are a family of cell penetrating peptides
      (CPPs) derived from crotamine, a rattlesnake venom toxin. They were named NrTPs
      for their remarkable nucleolus-homing properties and have been studied for their
      potential as drug delivery vehicles. Live cell microscopy experiments were
      conducted to monitor NrTP uptake and distribution in different cell types,
      including primary cells (PBMCs and erythrocytes) and different immortalized cell
      lines (HeLa, BHK21, BV-173, and MOLT-4). Uptake dependence on cell type (primary
      vs. immortalized, suspension vs. adherent, cancer vs. healthy cells), peptide
      concentration and cell viability were evaluated. To gain further insight on the
      internalization mechanism, uptake kinetics was also monitored. Results showed the
      uptake and distribution pattern as strongly dependent on peptide sequence,
      peptide concentration and membrane constituents. Under similar conditions, NrTP6
      is more internalized than NrTP1, NrTP2 and NrTP5. Additionally, while
      internalization of NrTP7 and NrTP8 may cause cytotoxicity, NrTP6 is noncytotoxic.
      Higher peptide concentrations can be correlated to nucleolar targeting, although
      even at low concentrations a residual number of cells reveal positive nucleolar
      labeling. NrTPs were successfully internalized into all cell types tested except
      erythrocytes.

PMID- 25620661
TI  - The prognostic value of reactive stroma on prostate needle biopsy: a population
      based study.
AB  - BACKGROUND: Reactive tumor stroma has been shown to play an active role in
      prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer
      (PC) has recently been established and found to predict biochemical recurrence
      and prostate cancer-specific mortality (PCSM) in prostatectomized patients. To
      the best of our knowledge, there has been no study investigating the prognostic
      value of reactive stromal grading (RSG) with regard to PCSM when evaluated in
      diagnostic prostate needle biopsies. METHODS: A population-based study on 318
      patients, encompassing all cases of PC diagnosed by needle biopsies and without
      evidence of systemic metastasis at the time of diagnosis in Aust-Agder County in
      the period 1991-1999. Patients were identified by cross-referencing the Cancer
      Registry of Norway. Clinical data were obtained by review of medical charts. The
      endpoint was PCSM. RSG was evaluated on haematoxylin and eosin stained sections
      according to previously described criteria; grade 0, 0-5% reactive stroma; grade
      1, 6-15%; grade 2, 16-50%; grade 3, 51-100%. RESULTS: RSG could be evaluated in
      278 patients. The median follow- up time was 110 months (interquartile range: 51
      171). The 10-year PC - specific survival rate for RSGs of 0, 1, 2, and 3 was 96%,
      81%, 69%, and 63%, respectively (P < 0.005). RSG remained independently
      associated with PCSM in a multivariate Cox regression analysis adjusting for
      prostate-specific antigen level, clinical stage, Gleason score, and mode of
      treatment. The concordance index of the multivariate model was 0.814 CONCLUSIONS:
      Our study demonstrates that RSG in diagnostic prostate needle biopsies predicts
      PCSM independently of other evaluable prognostic factors. Hence, RSG could be
      used in addition to traditional prognostic factors for prognostication and
      treatment stratification of PC patients.

PMID- 25620662
TI  - Comparison of the performance of 2 GFR estimating equations using creatinine and
      cystatin C to predict adverse outcomes in elderly individuals.

PMID- 25620663
TI  - Longitudinal associations among parental acceptance, familism values, and sibling
      intimacy in Mexican-origin families.
AB  - Prospective associations among parent-adolescent acceptance and familism values
      in early and middle adolescence and sibling intimacy in late adolescence and
      young adulthood were assessed in 246 Mexican-origin families. Older sibling
      gender and sibling gender constellation were investigated as moderators of these
      associations. Sibling intimacy was stable over time and younger siblings with
      older sisters reported higher levels of sibling intimacy than those with older
      brothers. As predicted, stronger familism values were associated with greater
      sibling intimacy, but this link was evident only for older sisters and for girl
      girl dyads. The links from mother- and father-acceptance to sibling intimacy also
      depended on the gender constellation of the sibling dyad: Higher levels of
      maternal warmth were associated with greater sibling intimacy for older sisters
      and girl-girl sibling pairs but higher levels of paternal warmth were linked to
      greater sibling intimacy only for older siblings in mixed-gender sibling dyads.
      Findings are consistent with prior research on the role of gender in family
      relationships but extend this work to encompass the effects of both parents' and
      siblings' gender, as well as the role of sociocultural values in parents'
      socialization influences. 

PMID- 25620664
TI  - The Ueno method for substaging pT1 colorectal adenocarcinoma by depth and width
      measurement: an interobserver study.
AB  - AIM: Early pT1 polyp colorectal cancers (CRCs) present challenges for accurate
      pathology substaging. Haggitt and Kikuchi stages depend on polyp morphology and
      are often difficult to apply due to suboptimal orientation or fragmentation, or
      absence of the muscularis propria in polypectomy or submucosal resection
      specimens. European guidelines for quality assurance suggest using Ueno's more
      objective approach, using depth and width measurements beyond muscularis mucosae.
      We have investigated interobserver variation using Ueno's approach. METHOD: Ten
      consecutive pT1 polyp CRCs were identified and the slides assessed by six
      gastrointestinal pathologists for depth and width of invasion. A further 60
      polyps were studied by a group of specialist and general pathologists. Agreement
      was assessed by analysis of variance. A polyp CRC is classified as high risk if
      it has a depth >= 2000 MUm or a width >= 4000 MUm and low risk with a depth <
      2000 MUm or a width < 4000 MUm. Concordance for the dichotomized values was
      assessed using the kappa statistic. RESULTS: The intraclass correlation
      coefficient (ICC) for depth was 0.83 and for width 0.56 in the 10-polyp group.
      The ICC for the 60-polyp CRCs was 0.67 for depth and 0.37 for width. In both
      groups, when polyp CRCs are divided into high- and low-risk categories based on
      depth, there was substantial and moderate agreement (kappa = 0.80 and 0.47) but
      only fair agreement when based on width (kappa = 0.34 and 0.35). CONCLUSION:
      Ueno's method has the advantage of being independent of polyp morphology. Our
      study shows better concordance for depth measurement and reproducibility in
      nonfragmented specimens, with poorer agreement when based on width.

PMID- 25620665
TI  - Sulfiredoxin-1 protects primary cultured astrocytes from ischemia-induced damage.
AB  - Astrocytes appear to be important regulators of the inflammatory events that
      occur in stroke. Sulfiredoxin-1 (Srxn1), an endogenous antioxidant protein,
      exhibits neuroprotective effects. Although the mechanism by which Srxn1
      negatively regulates oxidative and apoptotic pathways has been extensively
      characterized, the impact of Srxn1 on inflammation has not been well studied. In
      this study, we used oxygen-glucose deprivation followed by recovery (OGD/R) and
      hydrogen peroxide (H2O2) to mimic stress from cerebral ischemic damage on primary
      cultured astrocytes. We found that knockdown of Srxn1 by two shRNAs resulted in
      decreased cell viability of astrocytes. Decreased level of Srxn1 also correlated
      with excessive levels of proinflammatory cytokines and chemokines such as TNF
      alpha, MPO, IL-1beta, and IL-6. In addition, Srxn1 appeared to influence the
      strength of TLR4 signaling pathway; the expression of COX-2, IL-6, and NOS2 were
      strongly induced by OGD/R and H2O2 in astrocyte cultures with Srxn1-shRNAs. Our
      results suggested that loss of Srxn1 expression in astrocytes may cause excessive
      activation of inflammatory responses which contribute to OGD/R- and H2O2-induced
      cell death. Restoring Srxn1 function by gene therapy and/or pharmacology emerges
      as a promising strategy for the treatment of stroke and other chronic
      neurodegenerative diseases. 

PMID- 25620666
TI  - Global cPILOT analysis of the APP/PS-1 mouse liver proteome.
AB  - PURPOSE: A quantitative proteomics strategy called combined precursor isotopic
      labeling and isobaric tagging (cPILOT) was designed to discover alterations in
      the amyloid precursor protein/presenilin-1 (APP/PS-1) mouse liver proteome. The
      multiplexing strategy allows simultaneous quantitation of 12 samples in a single
      experiment. EXPERIMENTAL DESIGN: For cPILOT samples, six APP/PS-1 and six
      heterozygous mouse livers were modified using precursor dimethylation (pH 2.5)
      followed by isobaric tagging (pH 8.0). Samples were pooled, fractioned with
      strong cation exchange, and analyzed using RPLC-MS(3) for protein identification
      and relative quantitation. In order to increase proteome coverage, a two-tiered
      data collection strategy was employed. Six duplex precursor dimethylation
      experiments were also performed to verify cPILOT protein quantitation. RESULTS:
      The combination of cPILOT with precursor dimethylation data resulted in 2437
      total liver proteins identified and 77 differentially expressed proteins in
      APP/PS-1 liver. Differentially expressed proteins are involved in metabolic
      processes such as B-oxidation, pyruvate metabolism, and glucose regulation.
      CONCLUSIONS AND CLINICAL RELEVANCE: cPILOT expands protein quantitation using
      isobaric tags and can be applied to any clinical laboratory interested in
      enhanced multiplexing strategies. Differentially expressed proteins in APP/PS-1
      mouse liver suggest the potential use of ketone bodies to alleviate metabolic
      dysregulation in Alzheimer's disease brain. Our work also suggests alterations in
      the alanine cycle potentially leading to hyperammonia production, may contribute
      to Alzheimer's disease pathogenesis.

PMID- 25620667
TI  - Martin F. Kagnoff, MD, January 19, 1941--November 16, 2014.

PMID- 25620668
TI  - Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening
      population.
AB  - BACKGROUND & AIMS: Capsule colonoscopy is a minimally invasive imaging method. We
      measured the accuracy of this technology in detecting polyps 6 mm or larger in an
      average-risk screening population. METHODS: In a prospective study, asymptomatic
      subjects (n = 884) underwent capsule colonoscopy followed by conventional
      colonoscopy (the reference) several weeks later, with an endoscopist blinded to
      capsule results, at 10 centers in the United States and 6 centers in Israel from
      June 2011 through April 2012. An unblinded colonoscopy was performed on subjects
      found to have lesions 6 mm or larger by capsule but not conventional colonoscopy.
      RESULTS: Among the 884 subjects enrolled, 695 (79%) were included in the analysis
      of capsule performance for all polyps. There were 77 exclusions (9%) for
      inadequate cleansing and whole-colon capsule transit time fewer than 40 minutes,
      45 exclusions (5%) before capsule ingestion, 15 exclusions (2%) after ingestion
      and before colonoscopy, and 15 exclusions (2%) for site termination. Capsule
      colonoscopy identified subjects with 1 or more polyps 6 mm or larger with 81%
      sensitivity (95% confidence interval [CI], 77%-84%) and 93% specificity (95% CI,
      91%-95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%-86%) and
      97% specificity (95% CI, 96%-98%). Capsule colonoscopy identified subjects with 1
      or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%
      93) and 82% specificity (95% CI, 80%-83%), and 10 mm or larger with 92%
      sensitivity (95% CI, 82%-97%) and 95% specificity (95% CI, 94%-95%). Sessile
      serrated polyps and hyperplastic polyps accounted for 26% and 37%, respectively,
      of false-negative findings from capsule analyses. CONCLUSIONS: In an average-risk
      screening population, technically adequate capsule colonoscopy identified
      individuals with 1 or more conventional adenomas 6 mm or larger with 88%
      sensitivity and 82% specificity. Capsule performance seems adequate for patients
      who cannot undergo colonoscopy or who had incomplete colonoscopies. Additional
      studies are needed to improve capsule detection of serrated lesions.
      Clinicaltrials.gov number: NCT01372878.

PMID- 25620669
TI  - SAMP1/YitFc mice develop ileitis via loss of CCL21 and defects in dendritic cell
      migration.
AB  - BACKGROUND & AIMS: The lymphatic chemokine CCL21 is required for dendritic cell
      (DC) migration from tissues to lymph nodes, which helps establish tolerance to
      foreign yet harmless antigens. We demonstrate that CCL21 is almost completely
      absent from SAMP1/YitFc (SAMP) mice, which spontaneously develop chronic ileitis
      that resembles Crohn's disease, and that DC migration is severely impaired in
      these mice compared with AKR mice (controls). Toll-like receptor agonists like
      the Toll-like receptor 7 agonist R848 induce DC maturation and mobilization.
      METHODS: We collected intestinal and other tissues and mesenteric lymph nodes
      (MLN) from SAMP mice. Expression of CCL21 was measured by quantitative reverse
      transcription polymerase chain reaction and immunofluorescence analyses;
      spontaneous and induced migration of DCs were assessed by flow cytometry. We
      analyzed production of retinoic acid by DCs and their ability to induce
      development of regulatory T cells. Mice were fed R848 to determine its effects on
      migration of DCs and development of ileitis in SAMP mice. RESULTS: SAMP mice
      expressed almost no CCL21 in any tissue tested. Their CD11b(+)CD103(+) DCs were
      defective in migration from the ileal lamina propria to the MLN. DCs from SAMP
      mice also had a greatly reduced ability to produce retinoic acid and induce
      development of regulatory T cells compared with control mice. Young SAMP mice had
      reduced CCL21 expression and decreased DC migration before developing ileitis.
      Administration of R848 to adult SAMP mice increased migration of DC to the MLN
      and development of regulatory T cells there, and reduced the severity of ileitis.
      CONCLUSIONS: Loss of CCL21 signaling and DC migration is required for development
      of ileitis in SAMP mice. Reagents such as R848, which activate DC migration to
      the MLN, may be developed as treatments for patients with Crohn's disease.

PMID- 25620671
TI  - Prevalence and triage of first contact pelvic floor dysfunction complaints in
      male patients referred to a Pelvic Care Centre.
AB  - AIMS: (i) To describe and analyse pelvic floor dysfunction symptoms in men
      referred to a Pelvic Care Centre (PCC). (ii) To describe the triage process of
      the same patients based on response to a first-contact interview. METHODS: Triage
      started with a telephone interview using previously constructed questions, asking
      for six types of PF complaints during the preceding 6 months. If present,
      complaint severity was registered on a 0-10 scale. Next, these first-contact
      complaints were used to describe patient case mix profiles using cross-tabular
      analysis. Later on, at first PCC visit, an intake questionnaire regarding
      specific PF health problem(s) was filled out. This procedure contributed to a
      firm baseline characterization of the individual patient profile and a clinically
      valid allocation to structured, predefined assessment and treatment. RESULTS:
      From 2005 to 2013 985 first-time patients (mean age 58.2 years (SD 15.3) have
      been referred to the PCC. Most frequently mentioned complaints: voiding
      dysfunctions (73.9%), urinary incontinence (29.5%), sexual problems (16.6%),
      faecal incontinence (13.9%), constipation (9.6%), and prolapse (0.3%). A first
      appointment to a single specialist was determined in 805 (81.7%) patients, in 137
      (13.9%) consultation of >1 specialist. Data analysis revealed higher-order
      interactions between PF complaints, suggesting patient profile complexity and
      patient population heterogeneity. CONCLUSIONS: One out of seven PCC patients
      showed multifactorial problems, needing >1 specialist. PF complaints either
      turned out to stand alone or cluster with others, or even to strengthen, weaken,
      nullify or inverse relationships. Neurourol. Urodynam. 35:487-491, 2016. (c) 2015
      Wiley Periodicals, Inc.

PMID- 25620670
TI  - Measurement of fecal calprotectin improves monitoring and detection of recurrence
      of Crohn's disease after surgery.
AB  - BACKGROUND & AIMS: Crohn's disease (CD) usually recurs after intestinal
      resection; postoperative endoscopic monitoring and tailored treatment can reduce
      the chance of recurrence. We investigated whether monitoring levels of fecal
      calprotectin (FC) can substitute for endoscopic analysis of the mucosa. METHODS:
      We analyzed data collected from 135 participants in a prospective, randomized,
      controlled trial, performed at 17 hospitals in Australia and 1 hospital in New
      Zealand, that assessed the ability of endoscopic evaluations and step-up
      treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C
      reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were
      measured before surgery and then at 6, 12, and 18 months after resection of all
      macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after
      surgery in 90 patients and at 18 months after surgery in all patients. RESULTS:
      Levels of FC were measured in 319 samples from 135 patients. The median FC level
      decreased from 1347 MUg/g before surgery to 166 MUg/g at 6 months after surgery,
      but was higher in patients with disease recurrence (based on endoscopic analysis;
      Rutgeerts score, >=i2) than in patients in remission (275 vs 72 MUg/g,
      respectively; P < .001). Combined 6- and 18-month levels of FC correlated with
      the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD
      recurrence, but the CRP level and CDAI score did not. Levels of FC greater than
      100 MUg/g indicated endoscopic recurrence with 89% sensitivity and 58%
      specificity, and a negative predictive value (NPV) of 91%; this means that
      colonoscopy could have been avoided in 47% of patients. Six months after surgery,
      FC levels less than 51 MUg/g in patients in endoscopic remission predicted
      maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6
      months who stepped-up treatment, FC levels decreased from 324 MUg/g at 6 months
      to 180 MUg/g at 12 months and 109 MUg/g at 18 months. CONCLUSIONS: In this
      analysis of data from a prospective clinical trial, FC measurement has sufficient
      sensitivity and NPV values to monitor for CD recurrence after intestinal
      resection. Its predictive value might be used to identify patients most likely to
      relapse. After treatment for recurrence, the FC level can be used to monitor
      response to treatment. It predicts which patients will have disease recurrence
      with greater accuracy than CRP level or CDAI score.

PMID- 25620672
TI  - The impact of macrophage-cancer cell interaction on the efficacy of photodynamic
      therapy.
AB  - Macrophages are one of the principal host cell populations in solid tumors. They
      are capable, due to their plasticity, of acquiring phenotypes that either combat
      (M1 type) or promote (M2 type) neoplastic growth. These cells, known as tumor
      associated macrophages (TAMs), play complex but pivotal roles in the outcome of
      photodynamic therapy (PDT) of malignant lesions. Among the various parenchymal
      and stromal cell populations found in tumors, TAMs have been shown to have the
      greatest capacity for the uptake of systemically administered photosensitizers.
      Both the tumor-localizing property of photosensitizers and their tumor-localized
      fluorescence could be partly attributed to the activity of TAMs. Since resident
      TAMs with accumulated high photosensitizer content will sustain high degrees of
      PDT damage, this population (predominantly M2 in most tumors) is selectively
      destroyed, and during the ensuing inflammatory reaction is replaced with newly
      invading macrophages of M1 phenotype. These macrophages are sentinels responding
      to DAMP signals from PDT-treated tumor cells and in turn are mobilized to
      generate a variety of inflammatory/immune mediators and opsonins. They have a
      critical role in contributing to the therapeutic effect of PDT by mediating
      disposal of killed cancer cells and by processing/presenting tumor antigens to T
      lymphocytes. However, TAMs accumulating in the later post-PDT phase can acquire
      the M2 (healing) phenotype, and could have a role in tumor recurrence by
      releasing factors that promote angiogenesis and the survival/proliferation of
      remaining cancer cells. Various therapeutic strategies modulating TAM activity in
      the PDT response have potential for clinical use for improving PDT-mediated tumor
      control. 

PMID- 25620673
TI  - Sleep quality and correlates of poor sleep in patients with rheumatoid arthritis.
AB  - The objective of this study is to examine sleep quality and correlates of poor
      sleep in patients with rheumatoid arthritis (RA). Five hundred patients with RA
      were recruited from a rheumatology outpatient clinic and included in this cross
      sectional study. Sleep quality and disturbances were assessed using the
      Pittsburgh Sleep Quality Index (PSQI). Other instruments included the
      Multidimensional Fatigue Inventory, the Epworth Sleepiness Scale, and the Health
      Assessment Questionnaire. Disease activity was assessed according to disease
      activity score DAS28-CRP-based. Complete scores on PSQI were obtained from 384
      patients (77 %). In those, the prevalence of poor sleep (PSQI >5) was 61 %, and
      the mean global PSQI score was 7.54 (SD 4.17). A linear association was found
      between poor sleep and mental fatigue, reduced activity related to fatigue,
      physical fatigue, and general fatigue. Mental fatigue and general fatigue were
      independently associated with sleep quality, sleep latency, sleep duration, sleep
      efficiency, and daytime dysfunction. However, in the linear multivariate
      analysis, only general fatigue 1.06 (95 % CI 1.03-1.09) and mental fatigue 1.03
      (95 % CI 1.01-1.05) were found to be significant correlates for reporting poor
      sleep. This study shows that a majority of patients with RA experience poor sleep
      and that general fatigue and mental fatigue are associated with poor sleep.

PMID- 25620675
TI  - Successful electronic implementation of discharge referral decision support has a
      positive impact on 30- and 60-day readmissions.
AB  - In a quasi-experimental study, decision support software was installed in three
      hospitals to study the ability to scale (spread) its use from one hospital on
      paper to three hospitals as software, and to examine the effect on 30- and 60-day
      readmissions. The Discharge Decision Support System (D2S2) software analyzes data
      collected by nurses on admission with a proprietary risk assessment tool,
      identifies patients in need of post-acute care, and alerts discharge planners. On
      six intervention units, with a concurrent comparison group of 76 units, we
      examined the implementation experience and compared readmission outcomes before
      and after implementation. The software implementation finished one month ahead of
      schedule, and the software performed reliably. High-risk patients admitted in the
      experimental phase after implementation of D2S2 decision support had
      significantly fewer 30-day readmissions (a decrease from 22.2% to 9.4%). When
      high- and low-risk patients were analyzed together, D2S2 achieved a 33% relative
      reduction in 30-day readmissions (13.1 to 8.8%) and sustained a 37% relative
      reduction at 60 days. The software, available commercially through RightCare
      Solutions, was adopted by the health system and remains in use after 22 months.
      The D2S2 risk assessment tool can be installed easily in existing EHR systems.
      Future research will focus on how the tool influences discharge decision-making
      and how its accuracy can be improved in specific settings.

PMID- 25620676
TI  - A Facile Solvothermal Synthesis of Octahedral Fe3 O4 Nanoparticles.
AB  - Anisotropic Fe3 O4 octahedrons are obtained via a simple solvothermal synthesis
      with appropriate sizes for various technological applications. A complete suite
      of materials characterization methods confirms the magnetite phase for these
      structures, which exhibit substantial saturation magnetization and intriguing
      morphologies for a wide range of applications. 

PMID- 25620677
TI  - In vivo evaluation of anticonvulsant and antioxidant effects of phenobarbital
      microemulsion for transdermal administration in pilocarpine seizure rat model.
AB  - This study aimed to evaluate a microemulsion system (ME) containing phenobarbital
      in epilepsy model induced by pilocarpine in rats and to oxidative stress and
      histologic lesions in hippocampus. The microemulsion was applied to the shaved
      back of Wistar rats. The animals were divided into the following groups: control
      group (P400); ME50 40mg/kg, topically-t.p.; ME100, 40mg/kg, t.p.; EM50, 40mg/kg,
      t.p.; phenobarbital solution 40mg/kg (PS), oral. After 60min, behavioral changes
      were evaluated for 1h in the model of epileptical crisis induced by pilocarpine.
      Phenobarbital in microemulsion was able to increase the latency for status
      epilepticus (SE) (p<0.05), decrease the number of epileptical crisis (ME50:
      p<0.001; ME100: p<0.01) and decrease mortality rate by 80% compared to P400. In
      EM50 and PS groups, deaths were decreased by 53.3% and 100% respectively. The
      ME50 and ME100 groups were able to reduce oxidative stress in experimental
      animals when compared to the P400. The microemulsion was still capable of
      reducing neuronal damage in the hippocampal areas. The results of this study come
      in an innovative way, demonstrating the ability of transdermal ME50 and ME100 to
      reduce pilocarpine-induced epileptical crisis, oxidative stress, besides neuronal
      damages. 

PMID- 25620678
TI  - [Oct parameters as predictive factors for the visual outcome after ranibizumab
      therapy in neovascular age related macular degeneration].
AB  - OBJECTIVE: To evaluate macular morphological parameters measured by spectral
      domain optical coherence tomography (SD-OCT) as predictive factors of visual
      outcome in patients with exudative age-related macular degeneration (AMD) treated
      with ranibizumab. METHODS: A retrospective study was conducted on 47 patients
      diagnosed with exudative AMD and treated with intravitreal ranibizumab for twelve
      months. Central retinal thickness (CRT), extension and thickness of modifications
      secondary to neovascular process, and status of the bands corresponding to the
      external limiting membrane (ELM) and to the ellipsoid region of the
      photoreceptors (ISe) were evaluated by means of SD-OCT. The relationship between
      these variables and visual acuity was analyzed by statistical methods. RESULTS:
      At the time of the diagnosis, preservation of ELM and ISe bands, and CRT were
      correlated with initial visual acuity. Twelve months later, CRT and visual acuity
      were independent parameters. Bivariate relationship analysis showed a correlation
      between final visual acuity and the following parameters: initial CRT, initial
      ISe and ELM status, and ISe and ELM integrity after loading dose. Multiple
      regression analysis indicated that initial visual acuity and ISe band status
      after loading dose have a predictive value for final visual acuity. CONCLUSIONS:
      The status of ISe and ELM bands after twelve months of treatment with ranibizumab
      was associated with visual outcome. Initial visual acuity and status of the ISe
      band after loading dose are prognostic factors of final visual acuity.

PMID- 25620679
TI  - Shear-stress-mediated refolding of proteins from aggregates and inclusion bodies.
AB  - Recombinant protein overexpression of large proteins in bacteria often results in
      insoluble and misfolded proteins directed to inclusion bodies. We report the
      application of shear stress in micrometer-wide, thin fluid films to refold boiled
      hen egg white lysozyme, recombinant hen egg white lysozyme, and recombinant
      caveolin-1. Furthermore, the approach allowed refolding of a much larger protein,
      cAMP-dependent protein kinase A (PKA). The reported methods require only minutes,
      which is more than 100 times faster than conventional overnight dialysis. This
      rapid refolding technique could significantly shorten times, lower costs, and
      reduce waste streams associated with protein expression for a wide range of
      industrial and research applications. 

PMID- 25620681
TI  - In memoriam: Willard G. Manning, 1946-2014.

PMID- 25620680
TI  - Homozygosity mapping in an Irish ALS case-control cohort describes local
      demographic phenomena and points towards potential recessive risk loci.
AB  - Runs of homozygosity are common in European populations and are indicative of
      consanguinity, restricted population size and recessively inherited traits. Here,
      we map runs of homozygosity (ROHs) in an Irish case-control cohort for
      amyotrophic lateral sclerosis (ALS), a devastating neurological condition with
      high heritability yet only partially established genetic cause. We compare the
      extent of homozygosity in the Irish cohort with a large British cohort and
      observe that ROHs are longer and more frequent in the Irish population than in
      the British, and that extent of ROHs is correlated with demographic factors
      within the island of Ireland. ROHs are also longer and more frequent in ALS cases
      compared to population-matched controls, supporting the hypothesis that
      recessively inherited loci play a pathogenic role in ALS. Comparing homozygous
      haplotypes between cases and controls reveals several potential recessive risk
      loci for ALS, including a genomic interval spanning ARHGEF1, a compelling ALS
      candidate gene. 

PMID- 25620674
TI  - Molecular underpinnings of synaptic vesicle pool heterogeneity.
AB  - Neuronal communication relies on chemical synaptic transmission for information
      transfer and processing. Chemical neurotransmission is initiated by synaptic
      vesicle fusion with the presynaptic active zone resulting in release of
      neurotransmitters. Classical models have assumed that all synaptic vesicles
      within a synapse have the same potential to fuse under different functional
      contexts. In this model, functional differences among synaptic vesicle
      populations are ascribed to their spatial distribution in the synapse with
      respect to the active zone. Emerging evidence suggests, however, that synaptic
      vesicles are not a homogenous population of organelles, and they possess
      intrinsic molecular differences and differential interaction partners. Recent
      studies have reported a diverse array of synaptic molecules that selectively
      regulate synaptic vesicles' ability to fuse synchronously and asynchronously in
      response to action potentials or spontaneously irrespective of action potentials.
      Here we discuss these molecular mediators of vesicle pool heterogeneity that are
      found on the synaptic vesicle membrane, on the presynaptic plasma membrane, or
      within the cytosol and consider some of the functional consequences of this
      diversity. This emerging molecular framework presents novel avenues to probe
      synaptic function and uncover how synaptic vesicle pools impact neuronal
      signaling. 

PMID- 25620683
TI  - [Current standard of care for initial management of open fractures in emergency
      departments : A nationwide survey in German trauma centers].
AB  - BACKGROUND: Limiting the morbidity of open fractures requires highly specific
      initial treatment. In addition to a stringent surgical strategy, correct
      antibiotic prophylaxis seems to be associated with an improved outcome. In the
      current literature, the duration and type of antibiotic prophylaxis are under
      discussion. The aim of the study was to survey the current initial treatment
      regimes for open fractures in German emergency departments. MATERIAL AND METHODS:
      With an online-based anonymous 16-item questionnaire all 3006 members of the
      German Trauma Society were surveyed. A total of 585 questionnaires (19.5 %) were
      returned completed. This article presents a descriptive analysis of the current
      state of treatment. RESULTS: Mainly specialists (35 %), senior physicians (30 %)
      and chief physicians (17 %) answered as well as interns (8 %) and out-patient
      practitioners (10 %). Of the participants 65 % did not accept the classification
      of emergency services; however, 93 % carried out urgent or emergency surgery, 84
      % started an antibiotic prophylaxis in the emergency department and 63 % used a
      standard operating procedure (SOP). A total of 60 % used 1 antibiotic drug, 25 %
      used 2 and 15 % used 3 or more substances. An antibiotic treatment for more than
      3 days was performed by 60 % of participants. CONCLUSION: The early initiation of
      antibiotic prophylaxis seems to be the standard practice in German emergency
      departments as well as early surgery. Strategies to improve the communication
      between prehospital and in-hospital teams, as well as graded antibiotic
      prophylaxis depending on the severity of soft tissue damage are needed.

PMID- 25620682
TI  - Clinical outcomes associated with evolving treatment modalities and radiation
      techniques for base-of-tongue carcinoma: thirty years of institutional
      experience.
AB  - Curative treatment for base-of-tongue squamous cell carcinoma (BOT SCC) has
      evolved over time; however, comparative outcomes analysis for various treatment
      strategies is lacking. The authors reviewed the evolution of treatment modality
      and radiotherapy (RT) technique for 231 consecutive BOT SCC patients at our
      institution between 1981 and 2011. Treatment modalities included definitive
      chemoradiotherapy (chemoRT) (42%), definitive RT (33%), surgery followed by RT
      (20%), and surgery alone (5%). RT techniques included external beam plus
      interstitial brachytherapy (EBRT + IB) (37%), conventional EBRT (29%), intensity
      modulated radiation therapy +/- simultaneous integrated boost (IMRT +/- SIB)
      (34%). Clinical characteristics and outcomes were stratified by modality or RT
      technique. Treatment modality evolved from definitive RT (1980s-1990s) to
      definitive chemoRT (1990s-2000s). RT technique evolved from EBRT + IB (1980s
      1990s) to conventional EBRT (1990s-2000s) to IMRT + SIB (2000s). With median
      alive follow-up of 6 years (0.3-28 years), the 5-year LC, LRC, and OS rates were
      80%, 73%, and 51%. There was no difference in distribution of gender, age, stage
      among treatment modalities. Definitive chemoRT had improved LRC (HR 1.6) and OS
      (HR 1.7) compared to definitive RT. IMRT + SIB had improved LRC (HR 3.2), DFS (HR
      3.4), and OS (HR 3.0) compared to conventional EBRT. Over the past 30 years, BOT
      SCC treatment has undergone major paradigm shifts that incorporate nonsurgical
      functional preservation, concurrent chemotherapy, and advanced RT techniques.
      Excellent locoregional control and survival outcomes are associated with
      accelerated IMRT with chemotherapy.

PMID- 25620684
TI  - Electric-field-induced shift in the threshold voltage in LaAlO3/SrTiO3
      heterostructures.
AB  - The two-dimensional electron gas (2DEG) at the interface between insulating
      LaAlO3 and SrTiO3 is intriguing both as a fundamental science topic and for
      possible applications in electronics or sensors. For example, because the
      electrical conductance of the 2DEG at the LaAlO3/SrTiO3 interface can be tuned by
      applying an electric field, new electronic devices utilizing the 2DEG at the
      LaAlO3/SrTiO3 interface could be possible. For the implementation of field-effect
      devices utilizing the 2DEG, determining the on/off switching voltage for the
      devices and ensuring their stability are essential. However, the factors
      influencing the threshold voltage have not been extensively investigated. Here,
      we report the voltage-induced shift of the threshold voltage of Pt/LaAlO3/SrTiO3
      heterostructures. A large negative voltage induces an irreversible positive shift
      in the threshold voltage. In fact, after the application of such a large negative
      voltage, the original threshold voltage cannot be recovered even by application
      of a large positive electric field. This irreversibility is attributed to the
      generation of deep traps near the LaAlO3/SrTiO3 interface under the negative
      voltage. This finding could contribute to the implementation of nanoelectronic
      devices using the 2DEG at the LaAlO3/SrTiO3 interface. 

PMID- 25620685
TI  - Plantar pressure relief under the metatarsal heads: therapeutic insole design
      using three-dimensional finite element model of the foot.
AB  - Therapeutic footwear with specially-made insoles is often used in people with
      diabetes and rheumatoid arthritis to relieve ulcer risks and pain due to high
      pressures from areas beneath bony prominences of the foot, in particular to the
      metatarsal heads (MTHs). In a three-dimensional finite element study of the foot
      and footwear with sensitivity analysis, effects of geometrical variations of a
      therapeutic insole, in terms of insole thicknesses and metatarsal pad (MP)
      placements, on local peak plantar pressure under MTHs and stress/strain states
      within various forefoot tissues, were determined. A validated musculoskeletal
      finite element model of the human foot was employed. Analyses were performed in a
      simulated muscle-demanding instant in gait. For many design combinations,
      increasing insole thicknesses consistently reduce peak pressures and internal
      tissue strain under MTHs, but the effects reach a plateau when insole becomes
      very thick (e.g., a value of 12.7mm or greater). Altering MP placements, however,
      showed a proximally- and a distally-placed MP could result in reverse effects on
      MTH pressure-relief. The unsuccessful outcome due to a distally-placed MP may
      attribute to the way it interacts with plantar tissue (e.g., plantar fascia)
      adjacent to the MTH. A uniform pattern of tissue compression under metatarsal
      shaft is necessary for a most favorable pressure-relief under MTHs. The
      designated functions of an insole design can best be achieved when the insole is
      very thick, and when the MP can achieve a uniform tissue compression pattern
      adjacent to the MTH.

PMID- 25620687
TI  - Bayesian methods for setting sample sizes and choosing allocation ratios in phase
      II clinical trials with time-to-event endpoints.
AB  - Conventional phase II trials using binary endpoints as early indicators of a time
      to-event outcome are not always feasible. Uveal melanoma has no reliable
      intermediate marker of efficacy. In pancreatic cancer and viral clearance, the
      time to the event of interest is short, making an early indicator unnecessary. In
      the latter application, Weibull models have been used to analyse corresponding
      time-to-event data. Bayesian sample size calculations are presented for single
      arm and randomised phase II trials assuming proportional hazards models for time
      to-event endpoints. Special consideration is given to the case where survival
      times follow the Weibull distribution. The proposed methods are demonstrated
      through an illustrative trial based on uveal melanoma patient data. A procedure
      for prior specification based on knowledge or predictions of survival patterns is
      described. This enables investigation into the choice of allocation ratio in the
      randomised setting to assess whether a control arm is indeed required. The
      Bayesian framework enables sample sizes consistent with those used in practice to
      be obtained. When a confirmatory phase III trial will follow if suitable evidence
      of efficacy is identified, Bayesian approaches are less controversial than for
      definitive trials. In the randomised setting, a compromise for obtaining feasible
      sample sizes is a loss in certainty in the specified hypotheses: the Bayesian
      counterpart of power. However, this approach may still be preferable to running a
      single-arm trial where no data is collected on the control treatment. This
      dilemma is present in most phase II trials, where resources are not sufficient to
      conduct a definitive trial.

PMID- 25620686
TI  - 'Dopamine-first' mechanism enables the rational engineering of the norcoclaurine
      synthase aldehyde activity profile.
AB  - Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet-Spengler
      condensation of dopamine and an aldehyde, forming a substituted (S)
      tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity
      has led to NCS being used for both in vitro biocatalysis and in vivo recombinant
      metabolism. Future engineering of NCS activity to enable the synthesis of diverse
      tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and
      kinetics. We assess two proposed mechanisms for NCS activity: (a) one based on
      the holo X-ray crystal structure and (b) the 'dopamine-first' mechanism based on
      computational docking. Thalictrum flavum NCS variant activities support the
      dopamine-first mechanism. Suppression of the non-enzymatic background reaction
      reveals novel kinetic parameters for NCS, showing it to act with low catalytic
      efficiency. This kinetic behaviour can account for the ineffectiveness of
      recombinant NCS in in vivo systems, and also suggests NCS may have an in planta
      role as a metabolic gatekeeper. The amino acid substitution L76A, situated in the
      proposed aldehyde binding site, results in the alteration of the enzyme's
      aldehyde activity profile. This both verifies the dopamine-first mechanism and
      demonstrates the potential for the rational engineering of NCS activity. 

PMID- 25620688
TI  - Costs and health-related quality of life of patients with cystic fibrosis and
      their carers in France.
AB  - BACKGROUND: Our goal was to provide data on the economic burden and health
      related quality of life (HRQoL) associated with cystic fibrosis (CF) in France.
      METHODS: A retrospective cross-sectional study was carried out on adults and
      children with CF, who completed an anonymous questionnaire regarding their socio
      demographic characteristics, healthcare consumption and presence of a carer.
      Costs were calculated with a bottom-up approach, and HRQoL was assessed using EQ
      5D. RESULTS: 82 adults and 158 children were included. The total average annual
      cost of CF was ?29,746 per patient. Total costs were higher in adults than in
      children and increased with disease duration. The average utility was lower in
      adults (0.667 vs. 0.783 in children, p=0.0015). The HRQoL of carers was also
      affected (0.742 and 0.765 for carers of adults and children with CF,
      respectively). CONCLUSIONS: Our study highlights the burden of CF in terms of
      costs and decreased HRQoL for both patients and carers.

PMID- 25620689
TI  - MR findings associated with positive distraction of the hip joint achieved by
      axial traction.
AB  - PURPOSE: To determine which MR-arthrography findings are associated with positive
      hip joint distraction. MATERIALS AND METHODS: One hundred patients with MR
      arthrography of the hip using axial traction were included. Traction was applied
      during the MR examination with an 8 kg (females) or 10 kg (males) water bag,
      attached to the ankle over a deflection pulley. Fifty patients showing joint
      space distraction were compared to an age- and gender-matched control group of 50
      patients that did not show a joint distraction under axial traction. Two
      radiologists assessed the neck-shaft angle, lateral and anterior center-edge (CE)
      angles, CE angles in the transverse plane, extrusion index of the femoral head,
      acetabular depth, alpha angle, acetabular version, ligamentum teres, joint
      capsule and ligaments, iliopsoas tendon and the labrum. RESULTS: Mean joint space
      distraction in the study group was 0.9 +/- 0.6 mm. Patients with positive joint
      space distraction had significantly higher neck-shaft angles (control group 131.6
      +/- 5.4 degrees /study group 134.1 +/- 6.1 degrees , p < 0.05), smaller lateral
      CE angles (38.1 +/- 5.9 degrees /34.6 +/- 7.2 degrees , p < 0.05), smaller
      overall transverse CE angles (161.4 +/- 9.9 degrees /153.6 +/- 9.6 degrees , p <
      0.001), smaller acetabular depth (4.1 +/- 2.4 mm/5.8 +/- 2.5 mm, p < 0.01),
      higher alpha angles (53.5 +/- 7.8 degrees /59.2 +/- 10.1 degrees , p < 0.01) and
      a thicker ligamentum teres (4.7 +/- 1.4 mm/5.4 +/- 1.8 mm, p < 0.05). The other
      parameters revealed no significant differences. ICC values for interobserver
      agreement were 0.71-0.95 and kappa values 0.43-0.92. CONCLUSION: Increased neck
      shaft angles, small CE angles, small acetabular depth, higher alpha angles and a
      thick ligamentum teres are associated with positive joint distraction.

PMID- 25620690
TI  - Pseudocyclops: two cases of ACL graft partial tears mimicking cyclops lesions on
      MRI.
AB  - Arthroscopic reconstruction of the anterior cruciate ligament (ACL) using
      autografts or allografts is a common surgical procedure, particularly in young
      athletes. Although the procedure has excellent success rates, complications such
      as mechanical impingement, graft rupture, and arthrofibrosis can occur, often
      necessitating additional surgery. Magnetic resonance (MR) imaging has become a
      valuable tool in evaluating complications after ACL reconstruction. We report two
      cases of ACL reconstruction complicated by arthroscopically proven partial graft
      tears. In both cases the torn anterior graft fibers were flipped into the
      intercondylar notch, mimicking anterior arthrofibrosis, i.e., a "cyclops lesion,"
      on MR imaging. Careful review of the direction of graft fibers on MR imaging in
      the "pseudocyclops" lesions can help differentiate these partial tears from the
      fibrosis of a true cyclops. The "pseudocyclops" lesion is a previously
      undescribed MR imaging sign of partial ACL graft tear. Larger studies are
      required to determine the sensitivity and specificity of the sign, as well as the
      clinical importance of these partial graft tears. 

PMID- 25620691
TI  - Diagnosis and treatment of chorea syndromes.
AB  - Chorea is a common movement disorder which can be caused by a large variety of
      diseases including neurodegenerative diseases, metabolic diseases, and autoimmune
      diseases, or can be secondary to structural changes. The basal ganglia seem to be
      mainly involved in the pathophysiology indicating the vulnerability of this
      region. The diagnosis can be challenging, especially if chorea occurs during the
      treatment of neuropsychiatric conditions, and in these cases, it is difficult to
      distinguish between medication side effects (i.e., tardive dyskinesia) and the
      development of a neurodegenerative disease. Most therapeutic approaches are
      predominantly symptomatic, with a focus on multidisciplinary care for many
      patients. Nevertheless, some underlying diseases can be successfully treated and
      must not be missed. In this review, we summarize recent new developments in the
      differential diagnosis of chorea syndromes and suggest a pathway for a successful
      diagnosis of chorea in infancy, childhood, and adulthood for daily practice. 

PMID- 25620692
TI  - The application of a chemical determination of N-homocysteinylation levels in
      developing mouse embryos: implication for folate responsive birth defects.
AB  - Elevated homocysteine levels have long been associated with various disease
      states, including cardiovascular disease and birth defects, including neural tube
      defects (NTDs). One hypothesis regarding the strong correlation between these
      various disorders and high levels of homocysteine is that a reactive form of this
      small molecule can attach to mammalian proteins in a phenomenon known as
      homocysteinylation. These posttranslational modifications may become antigenic or
      may even directly disrupt certain protein function. It remains to be determined
      whether dietary influences that can cause globally increased levels of
      circulating homocysteine confer negative effects maternally, or may otherwise
      negatively and materially impact the metabolic balance in developing embryos.
      Herein we present the application of a chemical method of determination of N
      homocysteinylation to a set of neural tube closure stage mouse embryos and their
      mothers. We explore the uses of this newly described technique to investigate
      levels of maternal and embryonic N-homocysteinylation using dietary manipulations
      of one-carbon metabolism with two known folate-responsive NTD mouse models. The
      data presented reveal that although diet appeared to have significant effects on
      the maternal metabolic status, those effects did not directly correlate to the
      embryonic folate or N-homocysteinylation status. Our studies indicate that
      maternal diet and embryonic genotype most significantly affected the embryonic
      developmental outcome. 

PMID- 25620693
TI  - Protective effects of hydroxytyrosol-supplemented refined olive oil in animal
      models of acute inflammation and rheumatoid arthritis.
AB  - Virgin olive oil is the primary source of fat in the Mediterranean diet, and its
      beneficial health effects have been related with oleic acid and phenolic
      compounds content. Hydroxytyrosol, a typical virgin olive oil phenolic compound,
      has beneficial antioxidant and anti-inflammatory properties as previously
      reported. The aim of this study was to evaluate the effect of hydroxytyrosol
      supplemented refined olive oil at 0.5 and 5 mg/kg in a rodent model of rheumatoid
      arthritis. Rheumatoid arthritis was induced by intradermic administration, in
      male Wistar rats, of Freund's adjuvant with collagen type II on days 1 and 21.
      Hydroxytyrosol-supplemented refined olive oils were administrated by gavage from
      day 23 until day 35. The treatment at 5-mg/kg dose significantly decreased paw
      edema (P<.01), histological damage, cyclooxygenase-2 and inducible nitric oxide
      synthase expression, and markedly reduced the degree of bone resorption, soft
      tissue swelling and osteophyte formation, improving articular function in treated
      animals. Acute inflammation, induced by carrageenan, was also evaluated for
      hydroxytyrosol-supplemented refined olive oils at 0.5 and 5 mg/kg. Both doses
      significantly reduced paw edema (P<.001). Our results suggest that the
      supplementation of refined olive oil with hydroxytyrosol may be advantageous in
      rheumatoid arthritis with significant impact not only on chronic inflammation but
      also on acute inflammatory processes. 

PMID- 25620694
TI  - New learning following reactivation in the human brain: targeting emotional
      memories through rapid serial visual presentation.
AB  - Once reactivated, previously consolidated memories destabilize and have to be
      reconsolidated to persist, a process that might be altered non-invasively by
      interfering learning immediately after reactivation. Here, we investigated the
      influence of interference on brain correlates of reactivated episodic memories
      for emotional and neutral scenes using event-related potentials (ERPs). To
      selectively target emotional memories we applied a new reactivation method: rapid
      serial visual presentation (RSVP). RSVP leads to enhanced implicit processing
      (pop out) of the most salient memories making them vulnerable to disruption. In
      line, interference after reactivation of previously encoded pictures disrupted
      recollection particularly for emotional events. Furthermore, memory impairments
      were reflected in a reduced centro-parietal ERP old/new difference during
      retrieval of emotional pictures. These results provide neural evidence that
      emotional episodic memories in humans can be selectively altered through
      behavioral interference after reactivation, a finding with further clinical
      implications for the treatment of anxiety disorders. 

PMID- 25620696
TI  - Additive value of dobutamine stress echocardiography in patients with an
      anomalous origin of a coronary artery.
AB  - An anomalous origin of a coronary artery (AOCA) is the second most common cause
      of non-traumatic sudden cardiac death in young athletes. Patients with a
      malignant course of an AOCA of the right coronary artery only need surgical
      correction when myocardial ischaemia is detected. An AOCA and its malignant or
      benign course can be detected by coronary angiography, coronary computed
      tomography or cardiac magnetic resonance imaging. Detection of ischaemia can be
      more difficult since even a negative maximal-effort stress ECG does not exclude a
      potential lethal coronary anomaly. Also, there are no case series or trials
      showing sensitivity or specificity for any form of ischaemia detection for AOCA
      in the literature. Although not described previously in adults, dobutamine stress
      echocardiography was previously described in a paediatric population with AOCA.
      We are the first to describe ischaemia detection by dobutamine stress
      echocardiography in three adult patients with an AOCA of the right coronary
      artery who were subsequently referred for surgery. 

PMID- 25620695
TI  - A pan-Arctic synthesis of CH4 and CO2 production from anoxic soil incubations.
AB  - Permafrost thaw can alter the soil environment through changes in soil moisture,
      frequently resulting in soil saturation, a shift to anaerobic decomposition, and
      changes in the plant community. These changes, along with thawing of previously
      frozen organic material, can alter the form and magnitude of greenhouse gas
      production from permafrost ecosystems. We synthesized existing methane (CH4 ) and
      carbon dioxide (CO2 ) production measurements from anaerobic incubations of
      boreal and tundra soils from the geographic permafrost region to evaluate large
      scale controls of anaerobic CO2 and CH4 production and compare the relative
      importance of landscape-level factors (e.g., vegetation type and landscape
      position), soil properties (e.g., pH, depth, and soil type), and soil
      environmental conditions (e.g., temperature and relative water table position).
      We found fivefold higher maximum CH4 production per gram soil carbon from organic
      soils than mineral soils. Maximum CH4 production from soils in the active layer
      (ground that thaws and refreezes annually) was nearly four times that of
      permafrost per gram soil carbon, and CH4 production per gram soil carbon was two
      times greater from sites without permafrost than sites with permafrost. Maximum
      CH4 and median anaerobic CO2 production decreased with depth, while CO2 :CH4
      production increased with depth. Maximum CH4 production was highest in soils with
      herbaceous vegetation and soils that were either consistently or periodically
      inundated. This synthesis identifies the need to consider biome, landscape
      position, and vascular/moss vegetation types when modeling CH4 production in
      permafrost ecosystems and suggests the need for longer-term anaerobic incubations
      to fully capture CH4 dynamics. Our results demonstrate that as climate warms in
      arctic and boreal regions, rates of anaerobic CO2 and CH4 production will
      increase, not only as a result of increased temperature, but also from shifts in
      vegetation and increased ground saturation that will accompany permafrost thaw.

PMID- 25620697
TI  - Stent platforms anno 2015: is there still a place for bare metal stents at the
      front line?

PMID- 25620698
TI  - Phenotypic diversity and plasticity in circulating neutrophil subpopulations in
      cancer.
AB  - Controversy surrounds neutrophil function in cancer because neutrophils were
      shown to provide both pro- and antitumor functions. We identified a heterogeneous
      subset of low-density neutrophils (LDNs) that appear transiently in self
      resolving inflammation but accumulate continuously with cancer progression. LDNs
      display impaired neutrophil function and immunosuppressive properties,
      characteristics that are in stark contrast to those of mature, high-density
      neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor
      cells (MDSCs) and mature cells that are derived from HDNs in a TGF-beta-dependent
      mechanism. Our findings identify three distinct populations of circulating
      neutrophils and challenge the concept that mature neutrophils have limited
      plasticity. Furthermore, our findings provide a mechanistic explanation to
      mitigate the controversy surrounding neutrophil function in cancer. 

PMID- 25620699
TI  - A vitamin D receptor selectively activated by gemini analogs reveals ligand
      dependent and independent effects.
AB  - The bioactive form of vitamin D [1,25(OH)2D3] regulates mineral and bone
      homeostasis and exerts potent anti-inflammatory and antiproliferative properties
      through binding to the vitamin D receptor (VDR). The 3D structures of the VDR
      ligand-binding domain with 1,25(OH)2D3 or gemini analogs unveiled the molecular
      mechanism underlying ligand recognition. On the basis of structure-function
      correlations, we generated a point-mutated VDR (VDR(gem)) that is unresponsive to
      1,25(OH)2D3, but the activity of which is efficiently induced by the gemini
      ligands. Moreover, we show that many VDR target genes are repressed by unliganded
      VDR(gem) and that mineral ion and bone homeostasis are more impaired in VDR(gem)
      mice than in VDR null mice, demonstrating that mutations abolishing VDR ligand
      binding result in more severe skeletal defects than VDR null mutations. As gemini
      ligands induce VDR(gem) transcriptional activity in mice and normalize their
      serum calcium levels, VDR(gem) is a powerful tool to further unravel both
      liganded and unliganded VDR signaling.

PMID- 25620700
TI  - A genome-wide gene-expression analysis and database in transgenic mice during
      development of amyloid or tau pathology.
AB  - We provide microarray data comparing genome-wide differential expression and
      pathology throughout life in four lines of "amyloid" transgenic mice (mutant
      human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT
      gene). Microarray data were validated by qPCR and by comparison to human studies,
      including genome-wide association study (GWAS) hits. Immune gene expression
      correlated tightly with plaques whereas synaptic genes correlated negatively with
      neurofibrillary tangles. Network analysis of immune gene modules revealed six hub
      genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal
      network in TAU mice was similar except that Trem2 had hub status only in amyloid
      mice. The cortical network of TAU mice was entirely different with more hub genes
      and few in common with the other networks, suggesting reasons for specificity of
      cortical dysfunction in FTDP17. This Resource opens up many areas for
      investigation. All data are available and searchable at http://www.mouseac.org. 

PMID- 25620702
TI  - c-Abl regulates proteasome abundance by controlling the ubiquitin-proteasomal
      degradation of PSMA7 subunit.
AB  - The ubiquitin-proteasome system is a vital proteolytic pathway required for cell
      homeostasis. However, the turnover mechanism of the proteasome subunit itself is
      still not understood. Here, we show that the 20S proteasome subunit PSMA7 is
      subjected to ubiquitination and proteasomal degradation, which was suppressed by
      PSMA7 phosphorylation at Y106 mediated by the nonreceptor tyrosine kinases c
      Abl/Arg. BRCA1 specifically functions as an E3 ubiquitin ligase of PSMA7
      ubiquitination. c-Abl/Arg regulates cellular proteasome abundance by controlling
      the PSMA7 subunit supply. Downregulated PSMA7 level results in decreased
      proteasome abundance in c-Abl/Arg RNAi-knockdown or c-abl/arg-deficient cells,
      which demonstrated an increased sensitivity to proteasome inhibition. In response
      to oxidative stress, the c-Abl-mediated upregulation of proteasome level
      compensates for the proteasomal activity impairment induced by reactive oxygen
      species. Abl-kinases-regulated biogenesis and homeostasis of proteasome complexes
      may be important for understanding related diseases and pathological states.

PMID- 25620701
TI  - Dependence of brown adipose tissue function on CD36-mediated coenzyme Q uptake.
AB  - Brown adipose tissue (BAT) possesses the inherent ability to dissipate metabolic
      energy as heat through uncoupled mitochondrial respiration. An essential
      component of the mitochondrial electron transport chain is coenzyme Q (CoQ).
      While cells synthesize CoQ mostly endogenously, exogenous supplementation with
      CoQ has been successful as a therapy for patients with CoQ deficiency. However,
      which tissues depend on exogenous CoQ uptake as well as the mechanism by which
      CoQ is taken up by cells and the role of this process in BAT function are not
      well understood. Here, we report that the scavenger receptor CD36 drives the
      uptake of CoQ by BAT and is required for normal BAT function. BAT from mice
      lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered
      lipid metabolism, mitochondrial dysfunction, and defective nonshivering
      thermogenesis. Together, these data reveal an important new role for the systemic
      transport of CoQ to BAT and its function in thermogenesis. 

PMID- 25620703
TI  - Medial amygdalar aromatase neurons regulate aggression in both sexes.
AB  - Aromatase-expressing neuroendocrine neurons in the vertebrate male brain
      synthesize estradiol from circulating testosterone. This locally produced
      estradiol controls neural circuits underlying courtship vocalization, mating,
      aggression, and territory marking in male mice. How aromatase-expressing neuronal
      populations control these diverse estrogen-dependent male behaviors is poorly
      understood, and the function, if any, of aromatase-expressing neurons in females
      is unclear. Using targeted genetic approaches, we show that aromatase-expressing
      neurons within the male posterodorsal medial amygdala (MeApd) regulate components
      of aggression, but not other estrogen-dependent male-typical behaviors.
      Remarkably, aromatase-expressing MeApd neurons in females are specifically
      required for components of maternal aggression, which we show is distinct from
      intermale aggression in pattern and execution. Thus, aromatase-expressing MeApd
      neurons control distinct forms of aggression in the two sexes. Moreover, our
      findings indicate that complex social behaviors are separable in a modular manner
      at the level of genetically identified neuronal populations.

PMID- 25620704
TI  - Differential regulation of NF-kappaB-mediated proviral and antiviral host gene
      expression by primate lentiviral Nef and Vpu proteins.
AB  - NF-kappaB is essential for effective transcription of primate lentiviral genomes
      and also activates antiviral host genes. Here, we show that the early protein Nef
      of most primate lentiviruses enhances NF-kappaB activation. In contrast, the late
      protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-kappaB,
      even in the presence of Nef. Although this effect of Vpu did not correlate with
      its ability to interact with beta-TrCP, it involved the stabilization of IkappaB
      and reduced nuclear translocation of p65. Interestingly, however, Vpu did not
      affect casein kinase II-mediated phosphorylation of p65. Lack of Vpu was
      associated with increased NF-kappaB activation and induction of interferon and
      interferon-stimulated genes (ISGs) in HIV-1-infected T cells. Thus, HIV-1 and its
      simian precursors employ Nef to boost NF-kappaB activation early during the viral
      life cycle to initiate proviral transcription, while Vpu is used to downmodulate
      NF-kappaB-dependent expression of ISGs at later stages.

PMID- 25620706
TI  - Evaluation of Mycobacterium bovis double knockout mce2-phoP as candidate vaccine
      against bovine tuberculosis.
AB  - In this study, a Mycobacterium bovis knockout strain in phoP-phoR and mce2
      operons was tested as an antituberculosis experimental vaccine in animal models.
      The double mutant strain was significantly more attenuated than the wild type
      strain in inmunocompetent and inmunodeficient mice. Vaccination with the double
      mutant protected mice against challenge with a virulent M. bovis strain. 

PMID- 25620705
TI  - The alternative splicing regulator Tra2b is required for somitogenesis and
      regulates splicing of an inhibitory Wnt11b isoform.
AB  - Alternative splicing is pervasive in vertebrates, yet little is known about most
      isoforms or their regulation. transformer-2b (tra2b) encodes a splicing regulator
      whose endogenous function is poorly understood. Tra2b knockdown in Xenopus
      results in embryos with multiple defects, including defective somitogenesis.
      Using RNA sequencing, we identify 142 splice changes (mostly intron retention and
      exon skipping), 89% of which are not in current annotations. A previously
      undescribed isoform of wnt11b retains the last intron, resulting in a truncated
      ligand (Wnt11b-short). We show that this isoform acts as a dominant-negative
      ligand in cardiac gene induction and pronephric tubule formation. To determine
      the contribution of Wnt11b-short to the tra2b phenotype, we induce retention of
      intron 4 in wnt11b, which recapitulates the failure to form somites but not other
      tra2b morphant defects. This alternative splicing of a Wnt ligand adds intricacy
      to a complex signaling pathway and highlights intron retention as a regulatory
      mechanism.

PMID- 25620707
TI  - [Asthma relapse after surgical treatment of Cushing's syndrome].

PMID- 25620709
TI  - Inertial cavitation threshold of nested microbubbles.
AB  - Cavitation of ultrasound contrast agents (UCAs) promotes both beneficial and
      detrimental bioeffects in vivo (Radhakrishnan et al., 2013) [1]. The ability to
      determine the inertial cavitation threshold of UCA microbubbles has potential
      application in contrast imaging, development of therapeutic agents, and
      evaluation of localized effects on the body (Ammi et al., 2006) [2]. This study
      evaluates a novel UCA and its inertial cavitation behavior as determined by a
      home built cavitation detection system. Two 2.25 MHz transducers are placed at a
      90 degrees  angle to one another where one transducer is driven by a high voltage
      pulser and the other transducer receives the signal from the oscillating
      microbubble. The sample chamber is placed in the overlap of the focal region of
      the two transducers where the microbubbles are exposed to a pulser signal
      consisting of 600 pulse trains per experiment at a pulse repetition frequency of
      5 Hz where each train has four pulses of four cycles. The formulation being
      analyzed is comprised of an SF6 microbubble coated by a DSPC PEG-3000 monolayer
      nested within a poly-lactic acid (PLA) spherical shell. The effect of varying
      shell diameters and microbubble concentration on cavitation threshold profile for
      peak negative pressures ranging from 50 kPa to 2 MPa are presented and discussed
      in this paper. The nesting shell decreases inertial cavitation events from 97.96%
      for an un-nested microbubble to 19.09% for the same microbubbles nested within a
      2.53 MUm shell. As shell diameter decreases, the percentage of inertially
      cavitating microbubbles also decreases. For nesting formulations with average
      outer capsule diameters of 20.52, 14.95, 9.95, 5.55, 2.53, and 1.95 MUm, the
      percentage of sample destroyed at 1 MPa was 51.02, 38.94, 33.25, 25.27, 19.09,
      and 5.37% respectively.

PMID- 25620708
TI  - Clinical benefit in recurrent glioblastoma from adjuvant NovoTTF-100A and TCCC
      after temozolomide and bevacizumab failure: a preliminary observation.
AB  - The NovoTTF-100A is a device that emits alternating electric fields and it is
      approved for the treatment of recurrent glioblastoma. It works by perturbing
      tumor cells during mitosis as they enter anaphase leading to aneuploidy,
      asymmetric chromosome segregation and cell death with evidence of increased
      immunogenicity. Clinical trial data have shown equivalent efficacy when compared
      to salvage chemotherapies in recurrent disease. Responders were found to have had
      a lower dexamethasone usage and a higher rate of prior low-grade histology. We
      treated a series of patients with NovoTTF-100A and bevacizumab alone (n = 34) or
      in combination with a regimen consisting of 6-thioguanine, lomustine,
      capecitabine, and celecoxib (TCCC) (n = 3). Compared to the former cohort, the
      latter cohort exhibited a trend for prolonged overall survival, median 4.1 (0.3
      22.7) months versus 10.3 (7.7-13.6) months respectively (P = 0.0951), with one
      experiencing an objective response with a 50% reduction in tumor size on magnetic
      resonance imaging despite possessing a larger tumor size at baseline and more
      severe neurologic dysfunction than the median for either group. These
      observations illustrate the possibility of improving survival and achieving a
      response in patients with end-stage recurrent glioblastoma by biasing the tumor
      toward anti-tumor immunologic response with a combination of NovoTTF-100A and
      TCCC, as well as the continuation of bevacizumab in order to limit dexamethasone
      use due to its global immunosuppressive effect on the patient.

PMID- 25620710
TI  - The quasi-harmonic ultrasonic polar scan for material characterization:
      experiment and numerical modeling.
AB  - Conventionally, the ultrasonic polar scan (UPS) records the amplitude or time-of
      flight in transmission using short ultrasonic pulses for a wide range of
      incidence angles, resulting in a fingerprint of the critical bulk wave angles of
      the material at the insonified spot. Here, we investigate the use of quasi
      harmonic ultrasound (bursts) in a polar scan experiment, both experimentally and
      numerically. It is shown that the nature of the fingerprint drastically changes,
      and reveals the positions of the leaky Lamb angles. To compare with experiments,
      both plane wave and bounded beam simulations have been performed based on the
      recursive stiffness matrix method. Whereas the plane wave computations yield a
      pure Lamb wave angle fingerprint, this is no longer valid for the more realistic
      case of a bounded beam. The experimental recordings are fully supported by the
      bounded beam simulations. To complement the traditional amplitude measurement,
      experimental and numerical investigations have been performed to record, predict
      and analyze the phase of the transmitted ultrasonic beam. This results in the
      conceptual introduction of the 'phase polar scan', exposing even more intriguing
      and detailed patterns. In fact, the combination of the amplitude and the phase
      polar scan provides the complete knowledge about the complex transmission
      coefficient for every possible angle of incidence. This comprehensive information
      will be very valuable for inverse modeling of the local elasticity tensor based
      on a single UPS experiment. Finally, the UPS method has been applied for the
      detection of an artificial delamination. Compared to the pulsed UPS, the quasi
      harmonic UPS (both the amplitude and phase recording) shows a superior
      sensitivity to the presence of a delamination. 

PMID- 25620711
TI  - Embolic stroke during apixaban therapy for left atrial appendage thrombus.
AB  - Left atrial appendage (LAA) thrombus is associated with atrial fibrillation (AF)
      and is a powerful predictor of cardiogenic thromboembolism. Warfarin is an
      established anticoagulant therapy for patients with LAA thrombus to prevent
      thromboembolic complications. Apixaban is superior to warfarin in the prevention
      of thromboembolic complications in patients with AF, and there are case reports
      showing apixaban-associated resolution of LAA thrombus; however, the efficacy and
      safety of apixaban for the treatment of LAA thrombus remains unproven. Here we
      report a patient who experienced embolic stroke while taking apixaban for the
      treatment of LAA thrombus. Thrombolysis therapy was initiated at the onset of
      stroke and the patient recovered remarkably. Apixaban is known to make thrombi
      mobile and/or fragile by shifting the coagulation/fibrinolysis balance to a
      relative predominance of fibrinolytic activity; therefore, it is necessary to
      monitor for thromboembolic complications after the initiation of apixaban for the
      treatment of pre-existing LAA thrombus. 

PMID- 25620712
TI  - Elevated homocysteine levels contribute to larger hematoma volume in patients
      with intracerebral hemorrhage.
AB  - BACKGROUND: We investigate whether plasma homocysteine (HCY) levels are
      associated with hematoma volume and outcome in patients with intracerebral
      hemorrhage (ICH). METHODS: A total of 69 patients admitted within 24 hours after
      ICH onset was divided into 2 groups based on admission plasma HCY levels (low
      homocysteinemia [LHCY] group, plasma HCY concentrations <=14.62 MUmol/L, versus
      high homocysteinemia [HHCY] group, >14.62 MUmol/L). RESULTS: Mean hematoma
      volumes for 2 groups (LHCY and HHCY) were 13.18 and 23.09 mL (P = .012),
      respectively, in patients with thalamoganglionic ICH, but hematoma volumes
      between 2 groups had no significant difference among patients with lobar or
      infratentorial ICH. On multivariate linear regression analysis, elevated HCY
      levels significantly correlated with larger hematoma volume in patients with
      thalamoganglionic ICH (B = .604, P = .004) after adjustment for confounding
      factors. Poor outcomes (6-month modified Rankin Scale scores >=3) were not
      significantly different between 2 groups (low homocysteinemia group, 31.4%,
      versus high homocysteinemia group, 41.2%, P = .400). CONCLUSIONS: Elevated plasma
      HCY levels were associated with larger hematoma volume only in patients with
      thalamoganglionic ICH. HCY levels might not be predictors of the 6-month clinical
      outcome in patients with ICH.

PMID- 25620713
TI  - Intratumoral hemorrhage in a patient with malignant meningioma under
      anticoagulant therapy.
AB  - We report the case of an elderly woman with malignant meningioma and atrial
      fibrillation who started taking anticoagulants after an ischemic stroke and
      subsequently developed intratumoral hemorrhage. Further studies are required to
      confirm whether a particular anticoagulant agent is suitable for patients with
      brain tumor and atrial fibrillation. 

PMID- 25620714
TI  - Inhibition effect of graphene oxide on the catalytic activity of
      acetylcholinesterase enzyme.
AB  - Variations in the enzyme activity of acetylcholinesterase (AChE) in the presence
      of the nano-material, graphene oxide (GO), were investigated with the use of
      molecular spectroscopy UV-visible and fluorescence methods. From these studies,
      important kinetic parameters of the enzyme were extracted; these were the maximum
      reaction rate, Vm , and the Michaelis constant, Km . A comparison of these
      parameters indicated that GO inhibited the catalytic activity of the AChE because
      of the presence of the AChE-GO complex. The formation of this complex was
      confirmed with the use of fluorescence data, which was resolved with the use of
      the MCR-ALS chemometrics method. Furthermore, it was found that the resonance
      light-scattering (RLS) intensity of AChE changed in the presence of GO. On this
      basis, it was demonstrated that the relationship between AChE and GO was linear
      and such models were used for quantitative analyses of GO.

PMID- 25620715
TI  - Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of
      mutations associated with Primary Hyperoxaluria Type I: An overview.
AB  - Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44)
      catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a
      reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT
      gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder
      characterized by the deposition of calcium oxalate crystals primarily in the
      urinary tract. Here we describe the results obtained on the biochemical features
      of AGT as well as on the molecular and cellular effects of polymorphic and
      pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1
      emerges in which the co-inheritance of polymorphic changes and the condition of
      homozygosis or compound heterozygosis are two important factors that determine
      the enzymatic phenotype of PH1 patients. All the reported data represent relevant
      steps toward the understanding of genotype/phenotype correlations, the prediction
      of the response of the patients to the available therapies, and the development
      of new therapeutic approaches. This article is part of a Special Issue entitled:
      Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. 

PMID- 25620716
TI  - Outcomes of neurogenic bowel management in individuals living with a spinal cord
      injury for at least 10 years.
AB  - OBJECTIVE: To describe bowel management and its outcomes in individuals living
      with a spinal cord injury (SCI) for at least 10 years. DESIGN: Cross-sectional
      multicenter study. SETTING: Dutch community. PARTICIPANTS: Individuals (N=258;
      age range, 28-65y) who acquired their SCI between 18 and 35 years of age, who
      were at least 10 years post-SCI, and who used a wheelchair for their daily
      mobility. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The International
      SCI Bowel Function Basic Data Set, the neurogenic bowel dysfunction (NBD) score,
      and a single item on satisfaction with bowel management. RESULTS: Mean time since
      injury (TSI) was 24+/-9 years. Seventy-four percent used >=1 conservative bowel
      management method, specifically digital evacuation (35%) and mini enemas (31%).
      Transanal irrigation (TAI) and surgical interventions were used by 11% and 8%,
      respectively. Perianal problems were reported by 45% of the participants. Severe
      NBD was present in 36% of all participants and in 40% of those using a
      conservative method. However, only 14% were (very) dissatisfied with their
      current bowel management. Dissatisfaction with bowel management was significantly
      associated with constipation and severe NBD. With increasing TSI, there was a
      nonsignificant trend observed toward a decline in dissatisfaction with bowel
      management and a significant decline in severe NBD. CONCLUSIONS: Although
      satisfaction rates were high, more than a third of the participants reported
      severe NBD and perianal problems. Apart from severe NBD, there were no
      significant associations between bowel problems and TSI. Conservative methods
      were most often used, but some of these methods were also significantly
      associated with the presence of severe NBD. Longitudinal research is necessary to
      provide more knowledge concerning the course of NBD with increasing TSI.

PMID- 25620717
TI  - Evaluation of 3 pushrim-activated power-assisted wheelchairs in patients with
      spinal cord injury.
AB  - OBJECTIVE: To assess differences between manual wheelchairs and 3 pushrim
      activated power-assisted wheelchairs (PAPAWs): Servomatic A and B and E-motion.
      DESIGN: Repeated measures. SETTING: Rehabilitation hospital. PARTICIPANTS:
      Volunteers with spinal cord injuries (N=52). INTERVENTIONS: Ten subjects
      propelled the wheelchairs on a dynamometer, 46 evaluated each wheelchair on
      indoor and outdoor courses, and 10 evaluated their ability to transfer themselves
      and their wheelchairs into and out of their car. MAIN OUTCOME MEASURES: Oxygen
      consumption per unit time (Vo2) and heart rate were measured during propulsion on
      the dynamometer. Wheelchair efficiency on the indoor and outdoor courses was
      evaluated on the basis of heart rate, completion time, handrim push frequency,
      and patient satisfaction. RESULTS: On the dynamometer, decreases in Vo2 and heart
      rate were similar with the 3 PAPAWs compared with manual wheelchairs. On the
      outdoor course, heart rate was significantly decreased by PAPAWs compared with
      manual wheelchairs and patient satisfaction was better with Servomatic devices
      than with the E-motion device. Indoors, the course completion time was longer
      with the E-motion wheelchair than with other wheelchairs in the overall
      population, and handrim push frequency was higher with the E-motion wheelchair
      than with other wheelchairs in the subgroup with T12 to L1 injuries. Car transfer
      ability was lower with PAPAWs than with manual wheelchairs. CONCLUSIONS:
      Differences exist across PAPAWs. Compared with E-motion, the 2 Servomatic PAPAWs
      were easier to use outdoors, and difficulty transferring into/out of the car was
      similarly increased with all 3 PAPAWs.

PMID- 25620718
TI  - Single-fiber electromyography analysis of botulinum toxin diffusion in patients
      with fatigue and pseudobotulism.
AB  - OBJECTIVE: To characterize electromyographic abnormalities according to symptoms
      (asymptomatic, fatigue, pseudobotulism) reported 1 month after botulinum toxin
      injection. DESIGN: Retrospective, single-center study comparing single-fiber
      electromyography (SFEMG) in the extensor digitorum communis (EDC) or orbicularis
      oculi (OO) muscles. SETTING: Hospital. PARTICIPANTS: Four groups of adults
      treated for spasticity or neurologic bladder hyperactivity (N=55): control group
      (asymptomatic patients: n=17), fatigue group (unusual fatigue with no weakness:
      n=15), pseudobotulism group (muscle weakness and/or visual disturbance: n=20),
      and botulism group (from intensive care unit of the same hospital: n=3).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mean jitter, percentage of
      pathologic fibers, and percentage of blocked fibers were compared between groups.
      RESULTS: SFEMG was abnormal for 17.6% of control patients and 75% of patients in
      the pseudobotulism group. There were no differences between the control and
      fatigue groups. Mean jitter, percentage of pathologic fibers, and percentage of
      blocked fibers of the EDC muscle were significantly higher in the pseudobotulism
      group than in the fatigue and control groups. There were no differences between
      groups for the OO muscle. The SFEMG results in the botulism group were
      qualitatively similar to those of the pseudobotulism group. CONCLUSIONS: SFEMG of
      the EDC muscle confirmed diffusion of the toxin into muscles distant from the
      injection site in the pseudobotulism group. SFEMG in the OO muscle is not useful
      for the diagnosis of diffusion. No major signs of diffusion of botulinum toxin
      type A were found away from the injection site in patients with fatigue but no
      motor weakness. Such fatigue may be related to other mechanisms.

PMID- 25620719
TI  - Analysis of Pediatric Waist to Hip Ratio Relationship to Metabolic Syndrome
      Markers.
AB  - PURPOSE: Waist to hip ratio (WHR) is a valid assessment tool to determine risk
      for the development or presence of metabolic syndrome, diabetes, and
      cardiovascular disease in adults. Evidence-based research on its validity with
      children and adolescents is limited. A retrospective analysis was conducted to
      determine if WHR in overweight and obese pediatric patients is associated with
      metabolic syndrome laboratory markers. METHODS: Retrospective chart reviews were
      performed for 754 patients ages 6 to 17 years who were enrolled in a weight
      management program. Data collected included WHR, laboratory markers for metabolic
      disorder, body mass index, demographics, presence of acanthosis nigricans, and
      Tanner stage. RESULTS: WHR and high-density lipoprotein were negatively
      correlated, r (N = 597) = -0.20, p < .001. WHR and triglycerides were positively
      correlated, r (N = 597) = 0.19, p < .001, as were WHR and low-density
      lipoprotein, r (N = 596) = 0.09, p = .03, and WHR and insulin, r (N = 414) =
      0.16, p = .001. In a subject sample with very restricted range, a one-way
      analysis of variance found a significant effect of WHR on body mass index
      percentile, F (1, 754) = 22.43, p < .001, eta(2) = 0.03. CONCLUSIONS: Increased
      WHR correlated in children and adolescents with known indicators that could be
      suggestive of increased risk for metabolic syndrome, specifically low high
      density lipoprotein, high low-density lipoprotein, triglycerides, and insulin.
      These results suggest that evaluation of WHR may be a useful tool to indicate
      risk for developing metabolic syndrome and diabetes in children and adolescents.

PMID- 25620720
TI  - Pediatric nurses' differentiations between acceptable and unacceptable parent
      discipline behaviors: a Q-study.
AB  - BACKGROUND: Nurses are mandated to report suspected cases of child maltreatment.
      However, it is unclear how nurses decide what constitutes child abuse or evidence
      for reporting. It is crucial to examine how nurses define various forms of child
      maltreatment, including child abuse and its differentiation from physical
      discipline, to enhance our services to families with young children. OBJECTIVE:
      The present study examined pediatric nurses' views on acceptable versus
      unacceptable discipline behaviors to better understand parent behaviors that
      nurses are likely to deem reportable to child protective services. METHODS: Using
      Q methodology, a convenience sample of 48 pediatric nurses from one urban medical
      center sorted 71 statements related to the behavior or outcome of punishing a
      child via the Internet application FlashQ. The statements were sorted on a
      predefined continuum ranging from "Most Unacceptable" to "Most Acceptable." By
      person factor analysis was used to uncover groups of nurses with similar sorts
      and to generate a unique sort that represented the viewpoint of nurses in that
      group. RESULTS: Two distinct viewpoints were uncovered. Although there was
      consensus on what constitutes most acceptable and most unacceptable parent
      behaviors, nurses varied on their endorsement of using physical force as a form
      of discipline, suggesting a potential for discrepant tendencies to identify and
      report child abuse.

PMID- 25620721
TI  - IMMAN: free software for information theory-based chemometric analysis.
AB  - The features and theoretical background of a new and free computational program
      for chemometric analysis denominated IMMAN (acronym for Information theory-based
      CheMoMetrics ANalysis) are presented. This is multi-platform software developed
      in the Java programming language, designed with a remarkably user-friendly
      graphical interface for the computation of a collection of information-theoretic
      functions adapted for rank-based unsupervised and supervised feature selection
      tasks. A total of 20 feature selection parameters are presented, with the
      unsupervised and supervised frameworks represented by 10 approaches in each case.
      Several information-theoretic parameters traditionally used as molecular
      descriptors (MDs) are adapted for use as unsupervised rank-based feature
      selection methods. On the other hand, a generalization scheme for the previously
      defined differential Shannon's entropy is discussed, as well as the introduction
      of Jeffreys information measure for supervised feature selection. Moreover, well
      known information-theoretic feature selection parameters, such as information
      gain, gain ratio, and symmetrical uncertainty are incorporated to the IMMAN
      software ( http://mobiosd-hub.com/imman-soft/ ), following an equal-interval
      discretization approach. IMMAN offers data pre-processing functionalities, such
      as missing values processing, dataset partitioning, and browsing. Moreover,
      single parameter or ensemble (multi-criteria) ranking options are provided.
      Consequently, this software is suitable for tasks like dimensionality reduction,
      feature ranking, as well as comparative diversity analysis of data matrices.
      Simple examples of applications performed with this program are presented. A
      comparative study between IMMAN and WEKA feature selection tools using the Arcene
      dataset was performed, demonstrating similar behavior. In addition, it is
      revealed that the use of IMMAN unsupervised feature selection methods improves
      the performance of both IMMAN and WEKA supervised algorithms. Graphic
      representation for Shannon's distribution of MD calculating software. 

PMID- 25620722
TI  - Counteracting ammonia inhibition during anaerobic digestion by recovery using
      submersible microbial desalination cell.
AB  - Ammonia inhibition is one of the most frequent and serious problems in biogas
      plants. In this study, a novel hybrid system consisting of a submersible
      microbial desalination cell (SMDC) and a continuous stirred tank reactor (CSTR)
      was developed for counteracting ammonia inhibition during anaerobic digestion
      (AD) with simultaneous in situ ammonia recovery and electricity production. The
      SMDC was powered by acetate in a buffer solution, while synthetic ammonia-rich
      wastewater was used as the feeding of the CSTR. Under continuous operation,
      ammonia recovery rate of 86 g-N/m(2) /day and current density of 4.33 A/m(2) were
      achieved at steady-state condition. As a result, 112% extra biogas was produced
      due to ammonia recovery by the SMDC. High-throughput sequencing showed that
      ammonia recovery had an impact on the microbial community structures in the SMDC
      and CSTR. Considering the additional economic benefits of biogas enhancement and
      possible wastewater treatment, the SMDC may represent a cost-effective and
      environmentally friendly method for waste resources recovery and biomethanation
      of ammonia-rich residues.

PMID- 25620723
TI  - Variation in tobacco and mainstream smoke toxicant yields from selected
      commercial cigarette products.
AB  - There is a drive toward the mandated lowering and reporting of selected toxicants
      in tobacco smoke. Several studies have quantified the mainstream cigarette
      emissions of toxicants, providing benchmark levels. Few, however, have examined
      how measured toxicant levels within a single product vary over time due to
      natural variation in the tobacco, manufacturing and measurement. In a single
      centre analysis, key toxicants were measured in the tobacco blend and smoke of
      3R4F reference cigarette and three commercial products, each sampled monthly for
      10 months. For most analytes, monthly variation was low (coefficient of variation
      <15%); but higher (? 20%) for some compounds present at low (ppb) levels.
      Reporting toxicant emissions as a ratio to nicotine increased the monthly
      variation of the 9 analytes proposed for mandated lowering, by 1-2 percentage
      points. Variation in toxicant levels was generally 1.5-1.7-fold higher in
      commercial cigarettes compared with 3R4F over the 10-month period, but increased
      up to 3.5-fold for analytes measured at ppb level. The potential error (2CV)
      associated with single-point-in-time sampling averaged ~ 20%. Together, these
      data demonstrate that measurement of emissions from commercial cigarettes is
      associated with considerable variation for low-level toxicants. This variation
      would increase if the analyses were conducted in more than one laboratory.

PMID- 25620724
TI  - Mass spectrometry imaging for the proteomic study of clinical tissue.
AB  - Over the last decade, MALDI-MS imaging has been used by researchers to explore
      areas of proteomics, lipidomics and metabolomics in samples of clinical origin
      for both targeted and global biomarker analysis. Numerous technological
      advancements in MS and clinical tissue MS imaging have been accomplished; hence,
      in this article we aim to critically discuss whether MS imaging has now in fact
      become a true champion of the 'Omics Era'. In order to assess the potential for
      it to be routinely used in the clinical setting, it is pertinent to discuss some
      of its limitations, and to examine how these have been addressed by researchers.
      The key limitations of the technique we will discuss in this viewpoint article
      are as follows: sample throughput; relevance to patients, the availability of
      validated/standardised techniques; and integration with conventional pathology
      and other medical imaging techniques. Good progress has been made over the last 5
      years in overcoming these limitations that had previously restricted the use of
      this technology in the clinical setting.

PMID- 25620725
TI  - Rickia wasmannii increases the need for water in Myrmica scabrinodis (Ascomycota:
      Laboulbeniales; Hymenoptera: Formicidae).
AB  - The order Laboulbeniales (Fungi, Ascomycota) is a little-studied group of
      microscopic ectoparasites of invertebrates, mostly insects. The effects of
      Laboulbeniales species on their hosts are mostly unknown. Rickia wasmannii
      Cavara, 1899 is a common Laboulbeniales fungus occurring in Europe and is
      currently known to be a parasite of at least eight Myrmica ant species.
      R.wasmannii serves as a good model organism for Laboulbeniales-host interactions,
      as this species covers the host in a very high density, and infected host
      individuals can be easily collected in high numbers. The effect of R. wasmannii
      on the survival rate of its most common host species, Myrmica scabrinodis
      Nylander 1846, was therefore investigated in a laboratory experiment on an
      individual level. To enhance the results, environmental stresses were simulated
      by depriving infected and uninfected workers of water and food. The survival of
      individuals was recorded hourly until the death of the last individual. Infected
      specimens were significantly more sensitive to the withdrawal of food and water
      than uninfected specimens. When we tested for water consumption, we found that
      infected ants spent more time consuming water than uninfected ants. Therefore, it
      is possible that infected ants must replace the loss of water. Based on these
      results, R. wasmannii substantially decreases the chances and time of survival of
      infected individuals, at least in resource-limited environments, which suggest
      that R. wasmannii has a negative effect on its host. 

PMID- 25620726
TI  - A retrospective likelihood approach for efficient integration of multiple omics
      factors in case-control association studies.
AB  - Integrative omics, the joint analysis of outcome and multiple types of omics
      data, such as genomics, epigenomics, and transcriptomics data, constitute a
      promising approach for powerful and biologically relevant association studies.
      These studies often employ a case-control design, and often include nonomics
      covariates, such as age and gender, that may modify the underlying omics risk
      factors. An open question is how to best integrate multiple omics and nonomics
      information to maximize statistical power in case-control studies that ascertain
      individuals based on the phenotype. Recent work on integrative omics have used
      prospective approaches, modeling case-control status conditional on omics, and
      nonomics risk factors. Compared to univariate approaches, jointly analyzing
      multiple risk factors with a prospective approach increases power in
      nonascertained cohorts. However, these prospective approaches often lose power in
      case-control studies. In this article, we propose a novel statistical method for
      integrating multiple omics and nonomics factors in case-control association
      studies. Our method is based on a retrospective likelihood function that models
      the joint distribution of omics and nonomics factors conditional on case-control
      status. The new method provides accurate control of Type I error rate and has
      increased efficiency over prospective approaches in both simulated and real data.

PMID- 25620727
TI  - Health-promoting lifestyle behaviors and psychological status among Arabs and
      Koreans in the United Arab Emirates.
AB  - Cultural variations among ethnic groups may differentially influence health and
      health behavior. We explored and compared health-promoting lifestyle behaviors
      and psychological status, including depression, anxiety, and stress, among Korean
      migrants (n = 117) and Arab nationals (n = 103) in the United Arab Emirates
      (UAE). Pender's Health Promotion Model guided this research. The Health-Promoting
      Lifestyle Profile was used to measure health-promoting lifestyle behaviors and
      Lovibond and Lovibond's Depression, Anxiety, and Stress Scale to measure
      psychological status. The data were analyzed using bivariate procedures and
      multiple linear regression. No group differences were found in total scores for
      health-promoting lifestyle behaviors or psychological status. Both groups scored
      high on self-actualization and interpersonal support; Arabs scored low on
      exercise, and Koreans scored low on health responsibility. Across groups,
      psychological status (beta = -.390, p < .001), education (beta = .239, p < .001),
      and gender (beta = .238, p < .001) were significant determinants of health
      promoting lifestyle behaviors in multivariate analysis. Ethnicity and religious
      attendance were not significant determinants. Education level had a moderating
      effect; for those with a lower educational level, psychological distress had a
      stronger negative effect on health behavior. Findings suggest considering
      cultural aspects, such as different values placed on physical fitness and
      social/interpersonal relationships, in developing and implementing health
      education and/or promotion programs. Assessment of psychological status (i.e.,
      depression, anxiety, and stress) should also be included in health promotion
      programs and related health policies for Korean migrants and Arab nationals in
      the UAE.

PMID- 25620728
TI  - Ultrahigh Capacity Due to Multi-Electron Conversion Reaction in Reduced Graphene
      Oxide-Wrapped MoO2 Porous Nanobelts.
AB  - Multivalent transition metal oxides (MOx ) containing redox centers which can
      theoretically accept more than one electron have been suggested as promising
      anode materials for high-performance lithium ion batteries (LIBs). The Li-storage
      mechanism of these oxides is suggested to involve an unusual conversion reaction
      leading to the formation of metallic nanograins and Li2 O; however, a full-scale
      conversion reaction is seldom observed in molybdenum dioxide (MoO2 ) at room
      temperature due to slow kinetics. Herein, a full-scale multi-electron conversion
      reaction, leading to a high reversible capacity (974 mA h g(-1) charging capacity
      at 60 mA g(-1) ) in LIBs, is realized in a hybrid consisting of reduced graphene
      oxide (rGO) sheet-wrapped MoO2 porous nanobelts (rGO/MoO2 NBs). The rGO wrapping
      layers stabilize the nanophase transition in MoO2 and alleviate volume swing
      effects during lithiation/delithiation processes. This enables the hybrid to
      exhibit great cycle stability (tested to around 1900 cycles) and ultrafast rate
      capability (tested up to 50 A g(-1) ). 

PMID- 25620729
TI  - Social inequalities and smoking-associated breast cancer - Results from a
      prospective cohort study.
AB  - OBJECTIVE: The association between smoking and breast cancer has been found in
      most recent, large cohort studies. We wanted to investigate how smoking
      associated breast cancer varies by level of education, a well-established measure
      of socioeconomic status. METHODS: We included 302,865 women with 7490 breast
      cancer cases. Participants were assigned to low, moderate or high level of
      education and analyzed by smoking status (ever/never), and stratified by birth
      cohorts (<=1950>). We used Cox proportional hazard to estimate hazard ratios
      (HRs) and confidence intervals (CIs), adjusting for age, number of children, age
      at first childbirth, BMI, age at enrollment and physical activity. RESULTS: Women
      born <=1950 with low and moderate levels of education had a 40% increase in
      smoking-associated breast cancer risk (HR=1.40, 95% CI 1.25-1.57 and HR=1.14, 95%
      CI 1.05-1.24, respectively). Women in the same age group with high level of
      education did not have an increase in risk. No increased breast cancer risk was
      found among women born after 1950 for any level of education, when analyzed by
      smoking status. Longer duration of smoking before first childbirth was
      consistently associated with increasing risk of breast cancer in all three
      categories of education (all p for trends<0.01). CONCLUSION: Smoking for several
      years before first childbirth increases the risk of breast cancer, regardless of
      educational level.

PMID- 25620730
TI  - The power of the proposition: frequency of marijuana offers, parental knowledge,
      and adolescent marijuana use.
AB  - BACKGROUND: The frequency with which adolescents are offered marijuana has been
      investigated as a predictor of marijuana use. The current study was designed to
      test whether the number of marijuana offers received provides an indirect path
      between parental knowledge and adolescents' marijuana use. METHODS: Data from the
      nationally representative National Survey of Parents and Youth were examined.
      Analysis 1 tested the association between frequency of being offered marijuana
      and adolescents' (N=4264) marijuana usage in the subsequent year. Analysis 2,
      spanning a three-year time frame, tested whether the frequency of marijuana
      offers at the second year of the panel study bridged the relationship between
      parental knowledge in Year 1 and marijuana use in Year 3. RESULTS: Analysis 1
      indicated that the frequency with which adolescents were offered marijuana
      predicted usage one year later, after controlling for previous usage and nine
      other common predictors of marijuana use. Analysis 2 revealed an indirect
      relationship between parental knowledge and use through the number of marijuana
      offers the adolescent received. CONCLUSION: There was a strong link between the
      number of offers received and adolescents' future marijuana use. Higher parental
      knowledge predicted reductions in offer frequency, which was associated with
      lower levels of marijuana use. Reducing the number of marijuana offers an
      adolescent receives could serve as a useful focus for intervention programs
      targeting parents.

PMID- 25620731
TI  - Changes in alcohol consumption: United States, 2001-2002 to 2012-2013.
AB  - BACKGROUND: Documenting changes in alcohol consumption is critical for assessing
      future health service and alcohol treatment needs, evaluating efforts to modify
      drinking behavior and understanding the impact of shifting demographics and
      social norms. For the period since 2000, published data on drinking trends have
      been scarce and inconsistent. METHODS: Using data from two large, nationally
      representative surveys of U.S. adults (2001-2002 and 2012-2013) that contained
      virtually identical questions on consumption, we assessed differences by period
      in the prevalence of drinking, volume of intake, frequency of drinking and
      prevalence of >=monthly heavy episodic drinking (HED) and determined whether
      changes in consumption were consistent across beverage types and in population
      subgroups. RESULTS: Between 2001-2002 and 2012-2013, the prevalence of drinking
      increased, as did volume and frequency of drinking and prevalence of >=monthly
      HED among drinkers. Increases were greater for women than men for all measures
      and smaller among the formerly married for consumption among drinkers. The
      increase in overall drinking prevalence was magnified among all race-ethnic
      minorities, whereas the increase in >=monthly HED was magnified only among Blacks
      (all relative to Whites). CONCLUSIONS: Our findings are suggestive of a "wetter"
      drinking climate in 2012-2013 than in 2001-2002, indicating the need for
      continued and expanded efforts to prevent chronic and episodic heavy alcohol
      consumption. Given the across-the-board increases in alcohol consumption in
      recent years, policy efforts that address drinking at the population level are
      supported, even if specific drinking behaviors and subgroups of drinkers are
      additionally targeted for individualized approaches.

PMID- 25620732
TI  - Challenges to implementing opioid substitution therapy in Ukrainian prisons:
      Personnel attitudes toward addiction, treatment, and people with HIV/AIDS.
AB  - BACKGROUND: Ukraine is experiencing one of the most volatile HIV epidemics
      globally, fueled primarily by people who inject drugs (PWIDs), and a parallel
      incarceration epidemic. Opioid substitution therapy (OST) is internationally
      recognized as one of the most effective forms of treatment for opioid dependence
      and is among the most effective HIV prevention strategies available, yet efforts
      to adopt it in Ukraine's Criminal Justice System (CJS) have been thwarted.
      METHODS: To understand the reluctance of the Ukrainian CJS to adopt OST despite
      the overwhelming evidence pointing to its health benefits and improved criminal
      justice outcomes, we conducted the first survey of Ukrainian prison
      administrative, medical and custodial staff (N=243) attitudes towards addiction
      in general, OST, and people living with HIV/AIDS (PLWHA) in representative
      regions of Ukraine. RESULTS: Results revealed that Ukrainian CJS workers'
      attitudes toward OST, PLWHA, and drug addiction were universally negative, but
      differed substantially along geographic and occupational lines. Whereas
      geographic and cultural proximity to the European Union drove positive attitudes
      in the west, in the southern region we observed an identifiability effect, as
      workers who worked directly with prisoners held the most positive attitudes. We
      also found that knowledge mediated the effect of drug intolerance on OST
      attitudes. CONCLUSION: In Ukraine, adoption of OST is more influenced by myths,
      biases and ideological prejudices than by existing scientific evidence. By
      elucidating existing attitudes among CJS personnel, this study will help to
      direct subsequent interventions to address the barriers to implementing evidence
      based HIV prevention treatments.

PMID- 25620734
TI  - [Painful ischemic neuropathy].
AB  - Chronic ischemia in patients with peripheral arterial disease (PAD) represents a
      common medical problem. Neuropathic changes and pain caused by chronic ischemia
      are often found in the lower extremities of these patients. Pain in patients with
      chronic critical limb ischemia fulfill the criteria of neuropathic pain.
      Diagnostic tools besides medical history and examination are questionnaires,
      quantitative sensory testing (QST) and measuring intraepidermal nerve fiber
      density (IENFD) when indicated. A pharmacological approach with non-opioids and
      opioids as well as antidepressive and anticonvulsive drugs (according to the
      recommendations for the therapy of neuropathic pain) seems to be indicated for
      treating painful ischemic neuropathy. Spinal cord stimulation (SCS) provides the
      best evidence for invasive procedures in treating chronic ischemic pain. 

PMID- 25620733
TI  - CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type
      calcium channels.
AB  - BACKGROUND: Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of
      postsynaptic neuronal signaling networks. They play a key role in brain function,
      including fear memory and emotional and drug-taking behaviors. A whole-exome
      sequencing study identified a de novo mutation, p.A749G, in Cav1.3 alpha1
      subunits (CACNA1D), the second main LTCC in the brain, as 1 of 62 high risk
      conferring mutations in a cohort of patients with autism and intellectual
      disability. We screened all published genetic information available from whole
      exome sequencing studies and identified a second de novo CACNA1D mutation,
      p.G407R. Both mutations are present only in the probands and not in their
      unaffected parents or siblings. METHODS: We functionally expressed both mutations
      in tsA-201 cells to study their functional consequences using whole-cell patch
      clamp. RESULTS: The mutations p.A749G and p.G407R caused dramatic changes in
      channel gating by shifting (~15 mV) the voltage dependence for steady-state
      activation and inactivation to more negative voltages (p.A749G) or by pronounced
      slowing of current inactivation during depolarizing stimuli (p.G407R). In both
      cases, these changes are compatible with a gain-of-function phenotype.
      CONCLUSIONS: Our data, together with the discovery that Cav1.3 gain-of-function
      causes primary aldosteronism with seizures, neurologic abnormalities, and
      intellectual disability, suggest that Cav1.3 gain-of-function mutations confer a
      major part of the risk for autism in the two probands and may even cause the
      disease. Our findings have immediate clinical relevance because blockers of LTCCs
      are available for therapeutic attempts in affected individuals. Patients should
      also be explored for other symptoms likely resulting from Cav1.3 hyperactivity,
      in particular, primary aldosteronism.

PMID- 25620735
TI  - [Reality of treatment in psychotherapy: Results of a survey of German psychiatric
      hospitals].
AB  - OBJECTIVES: Since the introduction of the qualification as specialist for
      psychiatry and psychotherapy, in addition to psychopharmacotherapy psychotherapy
      is an integral component of the treatment of mentally ill people. A survey was
      carried out to evaluate the reality of clinical routine use of psychotherapy in
      German psychiatric hospitals. METHODS: Between October 2011 and March 2012 German
      hospitals of psychiatry and psychotherapy were contacted by the head
      organization, the conference of national directors (Bundesdirektorenkonferenz),
      to participate in a survey regarding the application of psychotherapy in the real
      clinical world of daily treatment. With an anonymous questionnaire, data were
      requested as either a printed form or online version. RESULTS: Data from 25
      psychiatric hospitals in the year 2010 could be analysed (average number of beds
      300 of which 53 were for psychosomatic/psychotherapeutic patients) and a total of
      87,000 inpatients were treated whereby 34 % were diagnosed as F1 addictive
      disorders and 24 % as F3 affective disorders. More than 80 % of the hospitals
      applied group therapies of relaxation, cognitive behavior therapy, social
      competence training and specific techniques, such as dialectic-behavior therapy.
      As individual treatment methods, patients with depressive disorders were treated
      with cognitive behavior therapy, interpersonal psychotherapy or psychodynamic
      therapy in more than 50 % of the cases. Relaxation techniques were offered in
      most cases by the nursing staff, behavior therapy by psychologists and physicians
      and psychodynamic therapy mainly by psychiatrists.

PMID- 25620736
TI  - alpha-TLR2 antibody attenuates the Abeta-mediated inflammatory response in
      microglia through enhanced expression of SIGIRR.
AB  - The immunoregulatory function of single-Ig-interleukin-1 related receptor
      (SIGIRR) is derived from its ability to constrain the inflammatory consequences
      of interleukin (IL)-1R and toll-like receptor (TLR)4 activation. This role
      extends to the brain, where SIGIRR deficiency increases the synaptic and
      cognitive dysfunction associated with IL-1R- and TLR4-mediated signalling. The
      current study set out to investigate the interaction between SIGIRR and TLR2 in
      brain tissue and the data demonstrate that the response to the TLR2 agonist,
      Pam3CysSK4 (Pam3Cys4), is enhanced in glial cells from SIGIRR(-/-) animals.
      Consistent with the view that beta-amyloid peptide (Abeta) signals through
      activation of TLR2, the data also show that Abeta-induced changes are exaggerated
      in glia from SIGIRR(-/-) animals. We report that microglia, rather than
      astrocytes, are the primary glial cell expressing both TLR2 and SIGIRR. While
      Abeta increased TLR2 expression, it decreased SIGIRR expression in microglia.
      This was mimicked by direct activation of TLR2 with Pam3Cys4. We investigated the
      effect of an anti-TLR2 antibody (alphaTLR2) on the Abeta-induced inflammatory
      responses and demonstrate that it prevented the expression and release of the pro
      inflammatory cytokines TNFalpha and IL-6 from microglia. In addition, application
      of alphaTLR2 alleviated the Abeta-mediated impairment in long-term potentiation
      (LTP) of hippocampal synaptic activity. The protective effects of alphaTLR2 were
      accompanied by an up-regulation in SIGIRR expression. We propose that a mechanism
      involving activation of PI3 kinase/Akt and the transcription factor peroxisome
      proliferator-activated receptor (PPAR)gamma may facilitate this increase in
      SIGIRR. These findings highlight a novel role of SIGIRR as a negative regulator
      of TLR2-mediated inflammation in the brain. 

PMID- 25620737
TI  - Effects of agricultural intensification on ability of natural enemies to control
      aphids.
AB  - Agricultural intensification through increasing fertilization input and cropland
      expansion has caused rapid loss of semi-natural habitats and the subsequent loss
      of natural enemies of agricultural pests. It is however extremely difficult to
      disentangle the effects of agricultural intensification on arthropod communities
      at multiple spatial scales. Based on a two-year study of seventeen 1500 m-radius
      sites, we analyzed the relative importance of nitrogen input and cropland
      expansion on cereal aphids and their natural enemies. Both the input of nitrogen
      fertilizer and cropland expansion benefited cereal aphids more than primary
      parasitoids and leaf-dwelling predators, while suppressing ground-dwelling
      predators, leading to an disturbance of the interspecific relationship. The
      responses of natural enemies to cropland expansion were asymmetric and species
      specific, with an increase of primary parasitism but a decline of predator/pest
      ratio with the increasing nitrogen input. As such, agricultural intensification
      (increasing nitrogen fertilizer and cropland expansion) can destabilize the
      interspecific relationship and lead to biodiversity loss. To this end,
      sustainable pest management needs to balance the benefit and cost of agricultural
      intensification and restore biocontrol service through proliferating the role of
      natural enemies at multiple scales. 

PMID- 25620738
TI  - Overexpression of microRNA-30a inhibits hepatitis B virus X protein-induced
      autophagosome formation in hepatic cells.
AB  - Hepatitis B virus (HBV) enters the host and survives by using several mechanisms.
      One of the ways that HBV survives and replicates in the host cells is by inducing
      autophagy. Previous reports have shown that microRNA (miRNA)-30a inhibits
      autophagosome formation in cancer cells. Hence, we hypothesized that
      overexpression of miRNA-30a could inhibit HBV-induced autophagosome formation in
      hepatic cells. To study this, both HepG2 cells and HepG2.2.1.5 cells (HBV
      expressing stable cell line) were transfected with miRNA-30a, and the cells were
      collected either for RNA isolation or protein isolation after 72 h of
      transfection. Beclin-1 expression was significantly higher in untransfected
      HepG2.2.1.5 cells than in HepG2 cells. Western blots showed that miRNA-30a
      overexpression resulted in a significant decrease in beclin-1 expression (eight
      fold and four-fold in HepG2 and HepG2.2.1.5 cells, respectively) and c-myc
      expression, whereas the numbers of terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL)-positive cells were increased. In contrast,
      overexpression of HBV X protein (HBx) in HepG2 cells resulted in the enhancement
      of beclin-1 (six-fold increase as compared with the empty vector-transfected
      cells) and c-myc expression, whereas the numbers of TUNEL-positive cells were
      reduced. To confirm these findings, HBx and miRNA-30a were coexpressed in HepG2
      cells, and the results showed significant inhibition of autophagosome formation
      and beclin-1 and c-myc expression, whereas apoptosis increased. These data
      demonstrate that HBx induces autophagosome formation via beclin-1 expression,
      whereas miRNA-30a overexpression could successfully inhibit the beclin-1
      expression induced by HBx, thereby modulating autophagosome formation in hepatic
      cells. 

PMID- 25620739
TI  - Determination of phosphatidylserine in milk-based nutritional products using
      online derivatization high-performance liquid chromatography.
AB  - Phosphatidylserine (PS) has received interest for its ability to improve
      cognitive abilities and behaviors. A new method for determining PS in milk-based
      nutritional products has been developed. The method includes a quick and simple
      sample preparation procedure, followed by high-performance liquid chromatography
      (HPLC) fluorescence detection (FLD) with an on-line 9-fluorenylmethyloxycarbonyl
      (FMOC) derivatization. The method allows PS to be determined in raw materials,
      milk powder and liquid milk products. The day-to-day (n=3 days) average recovery
      of over spike-in (at 100% PS content level) was 100%, and the method
      quantification limit is 53 mg per kg milk powder.

PMID- 25620740
TI  - Separating four diastereomeric pairs of dihydroflavonol glycosides from
      Engelhardia roxburghiana using high performance counter-current chromatography.
AB  - Four pairs of diastereomers were successfully isolated and separated from the
      water extract of Engelhardia roxburghiana by high performance counter-current
      chromatography (HPCCC) using a two-step procedure. The diastereomers were
      initially separated by a two-phase solvent system composed of n-hexane-n-butanol
      0.1% trifluoroacetic acid (1:2:3, v/v/v) and followed by the same solvent system
      using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as an additive. The
      chromatographic conditions, elution mode, and concentrations of the additive were
      refined. The two-step HPCCC isolation yielded 43.7mg (2S, 3S)-astilbin, 27.6mg
      (2R, 3R)-astilbin, 5.9mg (2S, 3R)-astilbin, 4.8mg (2R, 3S)-astilbin, 6.9mg (2S,
      3S)-engelitin, 3.1mg (2R, 3R)-engelitin, 8.2mg (2S, 3R)-engelitin, and 6.0mg (2R,
      3S)-engelitin from 384mg crude extract in four runs with purities of 99.3%,
      96.2%, 99.8%, 99.9%, 97.0%, 96.5%, 96.1%, and 96.8%, respectively. The present
      study revealed that HP-beta-CD can be used as an additive in HPCCC to effectively
      improve the resolution of the diastereomers. The established HPCCC method may
      serve as an approach to obtain high purity diastereomers on a large scale. 

PMID- 25620741
TI  - Embedment of Ag(I)-organic frameworks into silica gels for microextraction of
      polybrominated diphenyl ethers in soils.
AB  - Three Ag(I)-organic frameworks, [Ag5(pydc)2(CN)]n, {[Ag4(pydc)2]CH3CN}n, and
      [Ag(4,4'-bpy)NO3]n, were synthesized and embedded into silica gels to form metal
      organic-framework (MOF)-embedded gels for the microextraction of polybrominated
      diphenyl ethers (PBDEs) in soils. Despite the great differences in the structures
      of the organic ligands, all three Ag(I)-organic frameworks were found to
      effectively accumulate and concentrate PBDEs from sample solutions prepared with
      contaminated soil and purified water, indicating the important roles of Ag
      centers in PBDE extraction. Under the optimal experimental conditions (MOF mass,
      water volume, temperature, extraction time, and back-extraction time) for PBDE
      extraction from sample solutions, the detection limits of seven PBDEs (BDE-28,
      47, 99, 100, 153, 154, and 183) ranged from 0.01 to 2.6ngg(-1) for
      [Ag5(pydc)2(CN)]n, 0.20-0.64ngg(-1) for {[Ag4(pydc)2]CH3CN}n, and 0.60-3.08ngg(
      1) for [Ag(4,4'-bpy)NO3]n. The reproducibilities of the three methods were all
      satisfactory with relative standard deviations (RSDs) in the range of 2.2-9.6%,
      5.3-10.4%, and 6.9-9.4% for [Ag5(pydc)2(CN)]n, {[Ag4(pydc)2]CH3CN}n, and [Ag(4,4'
      bpy)NO3]n, respectively. The use of Ag(I)-organic frameworks for the
      microextraction of PBDEs was validated using both certified reference soils and
      field-contaminated soils, and the proposed methods are recommended as rapid and
      environmentally friendly alternatives for the extraction and determination of
      PBDEs in soils. 

PMID- 25620742
TI  - An investigation of the matrix sensitivity of refinery gas analysis using gas
      chromatography with flame ionisation detection.
AB  - The response of a flame ionisation detector (FID) on a gas chromatograph to
      methane, ethane, propane, i-butane and n-butane in a series of multi-component
      refinery gas standards was investigated to assess the matrix sensitivity of the
      instrument. High-accuracy synthetic gas standards, traceable to the International
      System of Units, were used to minimise uncertainties. The instrument response
      exhibited a small dependence on the component amount fraction: this behaviour,
      consistent with that of another FID, was thoroughly characterised over a wide
      range of component amount fractions and was shown to introduce a negligible bias
      in the analysis of refinery gas samples, provided a suitable reference standard
      is employed. No significant effects of the molar volume, density and viscosity of
      the gas mixtures on the instrument response were observed, indicating that the
      FID is suitable for the analysis of refinery gas mixtures over a wide range of
      component amount fractions provided that appropriate drift-correction procedures
      are employed. 

PMID- 25620743
TI  - Heterometal-organic frameworks as highly sensitive and highly selective
      luminescent probes to detect I- ions in aqueous solutions.
AB  - Two cationic heterometal-organic frameworks (Eu-Zn (1.NO3-) and Tb-Zn (2.NO3-))
      with NO3(-) counter-anions in the channels are structurally and luminously
      characterized. Both of them can serve as highly sensitive and highly selective
      luminescent probes for detecting I(-) ions in aqueous solutions. In particular,
      2.NO3- can selectively and reversibly detect I(-) with a fast response time of
      just 10 s and an extremely low detection limit of 0.001 ppm. Mechanism studies
      reveal that I(-) is quickly oxidized to form I3-with the help of 1.NO3- or 2.NO3
      , leading to luminescence quenching. This represents the first report of MOF
      based luminescent probes for the detection of I(-) in aqueous solutions.

PMID- 25620744
TI  - A Dirichlet process mixture model for survival outcome data: assessing nationwide
      kidney transplant centers.
AB  - Mortality rates are probably the most important indicator for the performance of
      kidney transplant centers. Motivated by the national evaluation of mortality
      rates at kidney transplant centers in the USA, we seek to categorize the
      transplant centers based on the mortality outcome. We describe a Dirichlet
      process model and a Dirichlet process mixture model with a half-cauchy prior for
      the estimation of the risk-adjusted effects of the transplant centers, with
      strategies for improving the model performance, interpretability, and
      classification ability. We derive statistical measures and create graphical tools
      to rate transplant centers and identify outlying groups of centers with
      exceptionally good or poor performance. The proposed method was evaluated through
      simulation and then applied to assess kidney transplant centers from a national
      organ failure registry.

PMID- 25620745
TI  - Preoperative planning before "sliding angulation osteotomy" for late-presenting
      Monteggia variant in children.

PMID- 25620746
TI  - Quantification of tibial bone loss in antegrade versus retrograde tunnel
      placement for anterior cruciate ligament reconstruction.
AB  - PURPOSE: Tibial bone destruction during primary graft tunnel placement and tibial
      bone loss following tunnel enlargement represent major challenges in revision
      reconstruction of the anterior cruciate ligament (ACL). Initial all-inside ACL
      reconstruction facilitates the preparation of tibial bone sockets rather than
      full tunnels that potentially preserve tibial bone stock. The purpose of this
      study was to comparatively assess length, diameter and volume of tibial graft
      tunnels following all-inside and conventional ACL reconstruction. METHODS:
      Postoperative computed tomography (CT) scans of 59 patients were assessed
      following ACL reconstruction. In 35 patients we used conventional antegrade
      tibial tunnel drilling and in 24 all-inside retrograde tibial bone sockets.
      Imaging analysis included total, minimal and maximal tunnel length and tunnel
      diameter. Tunnel volumes were calculated corresponding to these parameters.
      RESULTS: Statistically significant group differences (p < 0.01) could be detected
      for tibial tunnel volume, length and diameter between conventional antegrade and
      all-inside retrograde tibial bone tunnels and sockets, respectively. CONCLUSIONS:
      Compared with conventional techniques, all-inside retrograde drilling of tibial
      bone sockets is effective in preserving significant bone stock, which might be
      beneficial for revision reconstruction in cases of eventual primary graft
      failure.

PMID- 25620747
TI  - Adequate surgical treatment of periprosthetic femoral fractures following hip
      arthroplasty does not correlate with functional outcome and quality of life.
AB  - PURPOSE: This study aimed to analyse functional outcome and quality of life (QoL)
      after surgical treatment of periprosthetic femoral fractures (PPF) following
      total hip arthroplasty (THA). METHODS: This retrospective study assessed 67
      patients from 2005 to 2012. Epidemiologic data, surgical details, comorbidities,
      deaths and postoperative complications were recorded. Functional assessment
      included Harris Hip Score (HHS) and range of motion (ROM); QoL was assessed using
      the Short-Form Health Survey of 36 questions (SF-36) and Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) scores. RESULTS: Mean HHS was
      69 +/- 21 and ROM 96 degrees  +/- 17 degrees . Mean SF-36 and WOMAC scores
      revealed 44 +/- 7.2 and 18.9 +/- 19.6, respectively. The complication rate was
      25.4%; 23.7% of patients died. Analysis revealed no statistical influence on
      final outcome as a function of fracture type or treatment strategy. Comorbidities
      seem to influence functional outcome. CONCLUSION: PPF following THA are
      accompanied by a perceptible decline of function and remarkably high complication
      rates. In contrast to fracture classification and treatment type, American
      Society of Anesthesiologists (ASA) score predicts outcome.

PMID- 25620748
TI  - Authors response: the lateral femoral wall.

PMID- 25620749
TI  - Hypophosphatemic rickets: lessons from disrupted FGF23 control of phosphorus
      homeostasis.
AB  - Fibroblast growth factor-23 (FGF23) regulates phosphate reabsorption in the
      kidney and therefore plays an essential role in phosphate balance in humans.
      There is a host of defects that ultimately lead to excess FGF23 levels and
      thereby cause renal phosphate wasting and hypophosphatemic rickets. We describe
      the genetic, pathophysiologic, and clinical aspects of this group of disorders
      with a focus on X-linked hypophosphatemia (XLH), the best characterized of these
      abnormalities. We also discuss autosomal dominant hypophosphatemic rickets
      (ADHR), autosomal recessive hypophosphatemic rickets (ARHR) and tumor-induced
      osteomalacia (TIO) in addition to other rarer FGF23-mediated conditions. We
      contrast the FGF23-mediated disorders with FGF23-independent hypophosphatemia,
      specifically hypophosphatemic rickets with hypercalciuria (HHRH). Errant
      diagnosis of hypophosphatemic disorders is common. This review aims to enhance
      the recognition and appropriate diagnosis of hypophosphatemia and to guide
      appropriate treatment. 

PMID- 25620750
TI  - Cannabis cultivation in Quebec: between space-time hotspots and coldspots.
AB  - BACKGROUND: Cannabis cultivation has become increasingly localized, whether soil
      based or hydroponic growing methods are used. Characteristics of a given
      location, such as its climate and the equipment it requires may influence general
      accessibility or attract different types of offenders based on potential profits.
      The location of crops, especially hydroponic crops, suggests a certain proximity
      to the consumer market via semi-urban and urban environments, while making it
      possible to avoid detection. This article examines the cannabis market through
      its cultivation. METHODS: The stability of temporal and spatial clusters of
      cannabis cultivation, hotspots, and coldspots between 2001 and 2009 in the
      province of Quebec, Canada, are addressed. Studying the geography of crime is not
      a new endeavor, but coldspots are rarely documented in drug market research.
      Using arrests and general population data, as well as Kulldorff's scan
      statistics, results show that the temporal distribution of cannabis cultivation
      is highly seasonal for soil-based methods. RESULTS: Hydroponic production shows
      adaptation to its soil-based counterpart. Stable patterns are found for both
      spatial distributions. Hotspots for soil-based cultivation are found near several
      urban centers and the Ontario border. For hydroponic cannabis cultivation, a new
      hotspot suggests the emergence of an American demand for Quebec-grown cannabis
      between 2007 and 2009. Curiously, the region surrounding Montreal, the largest
      urban center in Quebec, is a recurrent and stable coldspot for both methods of
      cultivation. CONCLUSION: For all periods, spatial clusters are stronger for soil
      based methods than in the hydroponic context. Temporal differences and spatial
      similarities between soil-based cultivation and hydroponic cultivation are
      discussed. The role of the metropolis is also addressed.

PMID- 25620751
TI  - Monosomal karyotype at the time of diagnosis or transplantation predicts outcomes
      of allogeneic hematopoietic cell transplantation in myelodysplastic syndrome.
AB  - Various cytogenetic risk scoring systems may determine prognosis for patients
      with myelodysplastic syndromes (MDS). We evaluated 4 different risk scoring
      systems in predicting outcome after allogeneic hematopoietic cell transplantation
      (alloHCT). We classified 124 patients with MDS using the International Prognostic
      Scoring System (IPSS), the revised International Prognostic Scoring System (R
      IPSS), Armand's transplantation-specific cytogenetic grouping, and monosomal
      karyotype (MK) both at the time of diagnosis and at alloHCT. After adjusting for
      other important factors, MK at diagnosis (compared with no MK) was associated
      with poor 3-year disease-free survival (DFS) (27% [95% confidence interval, 12%
      to 42%] versus 39% [95% confidence interval, 28% to 50%], P = .02) and overall
      survival (OS) (29% [95% confidence interval, 14% to 44%] versus 47% [95%
      confidence interval, 36% to 59%], P = .02). OS but not DFS was affected by MK at
      alloHCT. MK frequency was uncommon in low-score R-IPPS and IPSS. Although IPSS
      and R-IPSS discriminated good/very good groups from poor/very poor groups,
      patients with intermediate-risk scores had the worst outcomes and, therefore,
      these scores did not show a progressive linear discriminating trend. Cytogenetic
      risk score change between diagnosis and alloHCT was uncommon and did not
      influence OS. MK cytogenetics in MDS are associated with poor survival,
      suggesting the need for alternative or intensified approaches to their treatment.

PMID- 25620752
TI  - "Awakening to" a new meaning of being at-risk for arrhythmogenic right
      ventricular cardiomyopathy: a grounded theory study.
AB  - Efforts of social scientists to understand how individuals living in a family at
      risk for a genetically linked condition make health care decisions, having
      brought to the forefront the contextual nature of risk perception. Using a
      grounded theory approach, this study examines the experiences of 29 individuals
      living in families at risk for arrhythmogenic right ventricular cardiomyopathy
      (ARVC). Attention is paid to how individuals (re)construct the meaning of being
      at risk in relation to the developing science of gene discovery. Findings
      highlight that individuals living in a family at risk for ARVC juxtapose existing
      scientific knowledge against experiential knowledge as they "awaken to" the fact
      that they or a family member are at risk. This process is pragmatic and fluid and
      contingent upon whether and how symptoms are aligned with the constructed image
      of the at-risk relative. 

PMID- 25620754
TI  - A systematic review and meta-analysis of changes in body weight in clinical
      trials of vegetarian diets.
AB  - In observational studies, vegetarians generally have lower body weights compared
      with omnivores. However, weight changes that occur when vegetarian diets are
      prescribed have not been well quantified. We estimated the effect on body weight
      when vegetarian diets are prescribed. We searched PubMed, EMBASE, and the
      Cochrane Central Register of Controlled Trials for articles through December 31,
      2013. Additional articles were identified from reference lists. We included
      intervention trials in which participants were adults, interventions included
      vegetarian diets of >=4 weeks' duration without energy intake limitations, and
      effects on body weight were reported. Two investigators independently extracted
      data using predetermined fields. Estimates of body weight change, comparing
      intervention groups to untreated control groups, were derived using a random
      effects model to estimate the weighted mean difference. To quantify effects on
      body weight of baseline weight, sex, age, study duration, study goals, type of
      diet, and study authorship, additional analyses examined within-group changes for
      all studies reporting variance data. We identified 15 trials (17 intervention
      groups), of which 4 included untreated controls. Prescription of vegetarian diets
      was associated with a mean weight change of -3.4 kg (95% CI -4.4 to -2.4;
      P<0.001) in an intention-to-treat analysis and -4.6 kg (95% CI -5.4 to -3.8;
      P<0.001) in a completer analysis (omitting missing post-intervention values).
      Greater weight loss was reported in studies with higher baseline weights, smaller
      proportions of female participants, older participants, or longer durations, and
      in studies in which weight loss was a goal. Using baseline data for missing
      values, I(2) equaled 52.3 (P=0.10), indicating moderate heterogeneity. When
      missing data were omitted, I(2) equaled 0 (P=0.65), indicating low heterogeneity.
      Studies are relatively few, with variable quality. The prescription of vegetarian
      diets reduces mean body weight, suggesting potential value for prevention and
      management of weight-related conditions. 

PMID- 25620753
TI  - The impact of eating frequency and time of intake on nutrient quality and Body
      Mass Index: the INTERMAP Study, a Population-Based Study.
AB  - BACKGROUND: Epidemiologic evidence is sparse on the effect of dietary behaviors
      and diet quality on body mass index (BMI; calculated as kg/m(2)), which can be
      important drivers of the obesity epidemic. OBJECTIVE: This study investigated the
      relationships of frequency of eating and time of intake to energy density,
      nutrient quality, and BMI using data from the International Study on
      Macro/Micronutrients and Blood Pressure including 2,696 men and women aged 40 to
      59 years from the United States and the United Kingdom. DESIGN: The International
      Study on Macro/Micronutrients and Blood Pressure is a cross-sectional
      investigation with four 24-hour dietary recalls and BMI measurements conducted
      between 1996 and 1999. Consumption of solid foods was aggregated into eating
      occasion. Nutrient density is expressed using the Nutrient Rich Food Index 9.3.
      The ratio of evening/morning energy intake was calculated; mean values of four
      visits were used. STATISTICAL ANALYSES PERFORMED: Characteristics across eating
      occasion categories are presented as adjusted mean with corresponding 95% CI.
      Multiple linear regression models were used to examine associations of eating
      occasions, ratio of evening/morning energy intake, dietary energy density, and
      Nutrient Rich Food Index 9.3 with BMI. RESULTS: Compared to participants with
      fewer than four eating occasions in 24 hours, those with six or more eating
      occasions in 24 hours had lower mean BMI (27.3 vs 29.0), total energy intake
      (2,129 vs 2,472 kcal/24 hours), dietary energy density (1.5 vs 2.1 kcal/g), and
      higher Nutrient Rich Food Index 9.3 (34.3 vs 28.1). In multiple regression
      analyses, higher evening intake relative to morning intake was directly
      associated with BMI; however, this did not influence the relationship between
      eating frequency and BMI. CONCLUSIONS: Our results suggest that a larger number
      of small meals may be associated with improved diet quality and lower BMI. This
      may have implications for behavioral approaches to controlling the obesity
      epidemic.

PMID- 25620755
TI  - Apheresis nursing: a Canadian perspective.

PMID- 25620756
TI  - Development of blood transfusion product pathogen reduction treatments: a review
      of methods, current applications and demands.
AB  - Transfusion-transmitted infections (TTI) have been greatly reduced in numbers due
      to the strict donor selection and screening procedures, i.e. the availability of
      technologies to test donors for endemic infections, and routine vigilance of
      regulatory authorities in every step of the blood supply chain (collection,
      processing and storage). However, safety improvement is still a matter of concern
      because infection zero-risk in transfusion medicine is non-existent. Alternatives
      are required to assure the safety of the transfusion product and to provide a
      substitution to systematic blood screening tests, especially in less-developed
      countries or at the war-field. Furthermore, the increasing mobility of the
      population due to traveling poses a new challenge in the endemic screening tests
      routinely used, because non-endemic pathogens might emerge in a specific
      population. Pathogen reduction treatments sum a plethora of active approaches to
      eliminate or reduce potential threatening pathogen load from blood transfusion
      products. Despite the success of pathogen reduction treatments applied to plasma
      products, there is still a long way to develop and deploy pathogen reduction
      treatments to cellular transfusion products (such as platelets, RBCs or even to
      whole blood) and there is divergence on its acceptance worldwide. While the use
      of pathogen reduction treatments in platelets is performed routinely in a fair
      number of European blood banks, most of these treatments are not (or just)
      licensed in the USA or elsewhere in the world. The development of pathogen
      reduction treatments for RBC and whole blood is still in its infancy and under
      clinical trials. In this review, we discuss the available and emerging pathogen
      reduction treatments and their advantages and disadvantages. Furthermore, we
      highlight the importance of characterizing standard transfusion products with
      current and emerging approaches (OMICS) and clinical outcome, and integrating
      this information on a database, thinking on the benefits it might bring in the
      future toward personalized transfusion therapies. 

PMID- 25620757
TI  - Scheme for the selection of measurement uncertainty models in blood
      establishments' screening immunoassays.
AB  - Blood establishments routinely perform screening immunoassays to assess safety of
      the blood components. As with any other screening test, results have an inherent
      uncertainty. In blood establishments the major concern is the chance of false
      negatives, due to its possible impact on patients' health. This article briefly
      reviews GUM and diagnostic accuracy models for screening immunoassays,
      recommending a scheme to support the screening laboratories' staffs on the
      selection of a model considering the intended use of the screening results (i.e.,
      post-transfusion safety). The discussion is grounded on a "risk-based thinking",
      risk being considered from the blood donor selection to the screening
      immunoassays. A combination of GUM and diagnostic accuracy models to evaluate
      measurement uncertainty in blood establishments is recommended. 

PMID- 25620758
TI  - HPA antibodies in Algerian multitransfused patients: Prevalence and involvement
      in platelet refractoriness.
AB  - BACKGROUND: Patients receiving cellular blood components may form HLA or HPA
      antibodies. The frequency and the specificity of HPA antibodies after a series of
      blood transfusions have never been reported in the Algerian population which is
      ethnically diverse and runs a higher risk of platelet alloimmunization due to
      high b allelic frequencies observed for the HPA systems. METHODS: 117
      polytransfused patients were included in this study; the detection of HPA
      antibodies was performed by the Monoclonal Antibody-specific Immobilization of
      Platelet Antigens method (MAIPA). Post-transfusion platelet effectiveness was
      evaluated by the calculation of corrected count increment (CCI). RESULTS: The
      antibodies against platelets were detected in 10.26% of the patients. In this
      study, the platelet systems concerned by the alloimmunizations were specifically
      HPA-1, -3 and -5 with particular predominance of HPA-1. Twenty two patients were
      refractory to platelet transfusion, as assessed by a CCI; in which 64% have
      factors associated with increased platelet consumption. Platelet Immunization was
      found in 14% of platelet refractoriness (PTR) cases. 03 Anti-platelet antibodies
      were directed against GPIb-IX (n = 1), anti-HPA-1b (n = 1) and anti HPA-5b (n =
      1) associated with anti-HLA antibodies in two cases. CONCLUSION: HLA and HPA
      alloimmunization is common among chronically transfused patients. PTR detection,
      identification of the underlying causes, and selection of the appropriate product
      for transfusion are fundamental to reduce the risk of major bleedings.

PMID- 25620759
TI  - Symptom clusters of gastrointestinal cancer patients undergoing radiotherapy
      using the Functional Living Index-Emesis (FLIE) quality-of-life tool.
AB  - OBJECTIVE: The Functional Living Index-Emesis (FLIE) instrument is a validated
      nausea and vomiting specific quality of life (QOL) tool originally created as a 3
      day test of the impact of chemotherapy-induced nausea and vomiting on cancer
      patients' daily life. The primary objective of the present study was to
      retrospectively explore the use of the FLIE from data obtained in a previously
      published study of patients with gastrointestinal radiation-induced nausea and
      vomiting (RINV) and compare the extracted symptom clusters on a weekly basis for
      the entirety of gastrointestinal cancer patients' radiotherapy treatments.
      METHODS: QOL was assessed on a weekly basis using the 18-item FLIE questionnaire
      for patients' radiotherapy treatments. A principal component analysis with
      varimax rotation was performed at each visit. The internal consistency and
      reliability of the derived clusters was assessed with Cronbach's alpha. Robust
      relationship and correlation among symptoms was displayed with biplot graphics.
      RESULTS: A total of 460 FLIE assessments were completed for the 86
      gastrointestinal patients who underwent radiotherapy. Two components were
      consistently identified except for week 5 where only one component was
      identified. Component 1 contained the items "Q10-Q18" which included all vomiting
      items. Component 2 included all nausea items from "Q1 to Q9". All the variables
      were well accounted for by two components for most weeks of treatment with
      excellent internal consistency. Biplots indicate that the two symptom clusters
      were evident at each week, with the exception of the first week of treatment.
      Strong correlations were seen between the effect of nausea on patients' ability
      to make meals, patients' ability to do tasks within the home, and patients'
      willingness to spend time with family and friends. CONCLUSION: The high internal
      consistency at all timepoints indicates that the FLIE QOL instrument is useful
      for the RINV population.

PMID- 25620760
TI  - [Iliopsoas muscle hematoma due to oral anticoagulant drugs].

PMID- 25620761
TI  - [Levofloxacin neurotoxicity: Presentation of a case and a literature review].

PMID- 25620762
TI  - [IBERICAN: The Spanish Framingham?].

PMID- 25620763
TI  - How Can a Large Left Atrial Myxoma Cause a Selective Mid-Diastolic Right-to-Left
      Atrial Shunt?

PMID- 25620764
TI  - Acute Drainage of Pericardial Effusion May Precipitate Right Ventricular Failure.

PMID- 25620765
TI  - A Prospective Randomized Study of Paravertebral Blockade in Patients Undergoing
      Robotic Mitral Valve Repair.
AB  - OBJECTIVE: The aim of this study was to evaluate the addition of paravertebral
      blockade to general anesthesia in patients undergoing robotic mitral valve
      repair. DESIGN: A randomized, prospective trial. SETTING: A single tertiary
      referral academic medical center. PARTICIPANTS: 60 patients undergoing robotic
      mitral valve surgery. INTERVENTIONS: Patients were randomized to receive 4-level
      paravertebral blockade with 0.5% bupivicaine before induction of general
      anesthesia. All patients were given a fentanyl patient-controlled analgesia upon
      arrival to the intensive care unit, and visual analog scale pain scores were
      queried for 24 hours. On postoperative day 2, patients were given an anesthesia
      satisfaction survey. MEASUREMENTS AND MAIN RESULTS: After obtaining institutional
      review board approval, surgical and anesthetic data were recorded perioperatively
      and compared between groups. Compared to general anesthesia alone, patients
      receiving paravertebral blockade and general anesthesia reported significantly
      less postoperative pain and required fewer narcotics intraoperatively and
      postoperatively. Patients receiving paravertebral blockade also reported
      significantly higher satisfaction with anesthesia. Successful extubation in the
      operating room at the conclusion of surgery was 90% and similar in both groups.
      Hospital length of stay also was similar. No adverse reactions were reported.
      CONCLUSIONS: The addition of paravertebral blockade to general anesthesia appears
      safe and can reduce postoperative pain and narcotic usage in patients undergoing
      minimally invasive cardiac surgery. These findings were similar to previous
      studies of patients undergoing thoracic procedures. Paravertebral blockade alone
      likely does not reduce hospital length of stay. This may be more closely related
      to early extubation, which is possible with or without paravertebral blockade.

PMID- 25620766
TI  - Intraoperative terlipressin therapy reduces the incidence of postoperative acute
      kidney injury after living donor liver transplantation.
AB  - OBJECTIVE: To evaluate the effect of intraoperative infusion with terlipressin on
      the incidence of acute kidney injury (AKI) after living donor liver
      transplantation (LDLT). DESIGN: Retrospective case-controlled study. SETTING:
      Government hospital. PARTICIPANTS: The medical records of 303 patients who
      underwent LDLT were reviewed retrospectively. INTERVENTIONS: Patients were
      divided into 2 groups on the basis of intraoperative administration of
      terlipressin. The primary outcome was AKI, as defined by the Acute Kidney Injury
      Network criteria. Secondary outcomes included the requirement for postoperative
      dialysis and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: The incidence
      of AKI was 38% (n = 115); AKI occurred in 24 (24.2%) patients who received
      terlipressin versus 91 (44.6%) in the control group (p = 0.001). The incidence of
      postoperative dialysis was 9.2% (n = 28). Postoperative dialysis was needed by 8
      patients (8.1%) in the terlipressin group versus 20 patients (9.8%) in the
      control group (p = 0.62). Multivariate logistic regression analysis indicated
      that terlipressin protected against AKI (odds ratio [OR], 0.4; 95% confidence
      interval [CI], 0.2-0.8; p = 0.013) but not the need for dialysis (OR, 0.7; 95%
      CI, 0.2-2.2; p = 0.53) or the in-hospital mortality (OR, 1.1; 95% CI, 0.5-2.3; p
      = 0.7). Adjustment, using the propensity score, did not alter the association
      between the use of terlipressin and AKI reduction (OR, 0.46; 95% CI, 0.22-0.89; p
      = 0.03). CONCLUSION: These results suggested that intraoperative terlipressin
      therapy is associated with significant reductions in the risk of AKI in LDLT
      patients.

PMID- 25620768
TI  - The role of ABA recycling and transporter proteins in rapid stomatal responses to
      reduced air humidity, elevated CO2, and exogenous ABA.

PMID- 25620769
TI  - Genomic, Transcriptomic, and Phenomic Variation Reveals the Complex Adaptation of
      Modern Maize Breeding.
AB  - The temperate-tropical division of early maize germplasms to different
      agricultural environments was arguably the greatest adaptation process associated
      with the success and near ubiquitous importance of global maize production.
      Deciphering this history is challenging, but new insight has been gained from
      examining 558 529 single nucleotide polymorphisms, expression data of 28 769
      genes, and 662 traits collected from 368 diverse temperate and tropical maize
      inbred lines in this study. This is a new attempt to systematically exploit the
      mechanisms of the adaptation process in maize. Our results indicate that
      divergence between tropical and temperate lines apparently occurred 3400-6700
      years ago. Seven hundred and one genomic selection signals and transcriptomic
      variants including 2700 differentially expressed individual genes and 389 rewired
      co-expression network genes were identified. These candidate signals were found
      to be functionally related to stress responses, and most were associated with
      directionally selected traits, which may have been an advantage under widely
      varying environmental conditions faced by maize as it was migrated away from its
      domestication center. Our study also clearly indicates that such stress
      adaptation could involve evolution of protein-coding sequences as well as
      transcriptome-level regulatory changes. The latter process may be a more flexible
      and dynamic way for maize to adapt to environmental changes along its short
      evolutionary history. 

PMID- 25620770
TI  - Growth-Regulating Factors (GRFs): A Small Transcription Factor Family with
      Important Functions in Plant Biology.
AB  - Growth-regulating factors (GRFs) are plant-specific transcription factors that
      were originally identified for their roles in stem and leaf development, but
      recent studies highlight them to be similarly important for other central
      developmental processes including flower and seed formation, root development,
      and the coordination of growth processes under adverse environmental conditions.
      The expression of several GRFs is controlled by microRNA miR396, and the GRF
      miRNA396 regulatory module appears to be central to several of these processes.
      In addition, transcription factors upstream of GRFs and miR396 have been
      discovered, and gradually downstream target genes of GRFs are being unraveled.
      Here, we review the current knowledge of the biological functions performed by
      GRFs and survey available molecular data to illustrate how they exert their roles
      at the cellular level. 

PMID- 25620771
TI  - Raman spectroscopy detection of phytic acid in plant seeds reveals the absence of
      inorganic polyphosphate.

PMID- 25620767
TI  - T cell exhaustion during persistent viral infections.
AB  - Although robust and highly effective anti-viral T cells contribute to the
      clearance of many acute infections, viral persistence is associated with the
      development of functionally inferior, exhausted, T cell responses. Exhaustion
      develops in a step-wise and progressive manner, ranges in severity, and can
      culminate in the deletion of the anti-viral T cells. This disarming of the
      response is consequential as it compromises viral control and potentially serves
      to dampen immune-mediated damage. Exhausted T cells are unable to elaborate
      typical anti-viral effector functions. They are characterized by the sustained
      upregulation of inhibitory receptors and display a gene expression profile that
      distinguishes them from prototypic effector and memory T cell populations. In
      this review we discuss the properties of exhausted T cells; the virological and
      immunological conditions that favor their development; the cellular and molecular
      signals that sustain the exhausted state; and strategies for preventing and
      reversing exhaustion to favor viral control. 

PMID- 25620772
TI  - Effects of ursolic acid on the structural and morphological behaviours of
      dipalmitoyl lecithin vesicles.
AB  - Effects of ursolic acid on the structural and morphological characteristics of
      dipalmitoyl lecithin(DPPC)-water system was studied by using differential
      scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS),
      freeze-fracture method combined with transmission electron-microscopy (FF-TEM)
      and infrared spectroscopy (FT-IR). The surface of the uncorrelated lipid system
      is rippled or grained and a huge number of small, presumably unilamellar vesicles
      are present if the UA/DPPC molar ratio is 0.1 mol/mol or higher. Besides the
      destroyed layer packing of regular multilamellar vesicles, non-bilayer (e.g.
      cubic or hexagonal) local structures are evidenced by SAXS and FF-TEM methods.
      The ability of UA to induce non-bilayer structures in hydrated DPPC system
      originates from the actual geometry form of associated lipid and UA molecules as
      concluded from the FT-IR measurements and theoretical calculations. Beside
      numerous beneficial e.g. chemopreventive and chemotherapeutic effect of ursolic
      acid against cancer, their impact to modify the lipid bilayers can be utilized in
      liposomal formulations.

PMID- 25620773
TI  - Effect of neurosteroids on a model lipid bilayer including cholesterol: An Atomic
      Force Microscopy study.
AB  - Amphiphilic molecules which have a biological effect on specific membrane
      proteins, could also affect lipid bilayer properties possibly resulting in a
      modulation of the overall membrane behavior. In light of this consideration, it
      is important to study the possible effects of amphiphilic molecule of
      pharmacological interest on model systems which recapitulate some of the main
      properties of the biological plasma membranes. In this work we studied the effect
      of a neurosteroid, Allopregnanolone (3alpha,5alpha-tetrahydroprogesterone or
      Allo), on a model bilayer composed by the ternary lipid mixture DOPC/bSM/chol. We
      chose ternary mixtures which present, at room temperature, a phase coexistence of
      liquid ordered (Lo) and liquid disordered (Ld) domains and which reside near to a
      critical point. We found that Allo, which is able to strongly partition in the
      lipid bilayer, induces a marked increase in the bilayer area and modifies the
      relative proportion of the two phases favoring the Ld phase. We also found that
      the neurosteroid shifts the miscibility temperature to higher values in a way
      similarly to what happens when the cholesterol concentration is decreased.
      Interestingly, an isoform of Allo, isoAllopregnanolone (3beta,5alpha
      tetrahydroprogesterone or isoAllo), known to inhibit the effects of Allo on GABAA
      receptors, has an opposite effect on the bilayer properties. 

PMID- 25620774
TI  - Multiple effects of anthracene-9-carboxylic acid on the TMEM16B/anoctamin2
      calcium-activated chloride channel.
AB  - Ca(2+)-activated Cl(-) currents (CaCCs) play important roles in many
      physiological processes. Recent studies have shown that TMEM16A/anoctamin1 and
      TMEM16B/anoctamin2 constitute CaCCs in several cell types. Here we have
      investigated for the first time the extracellular effects of the Cl(-) channel
      blocker anthracene-9-carboxylic acid (A9C) and of its non-charged analogue
      anthracene-9-methanol (A9M) on TMEM16B expressed in HEK 293T cells, using the
      whole-cell patch-clamp technique. A9C caused a voltage-dependent block of outward
      currents and inhibited a larger fraction of the current as depolarization
      increased, whereas the non-charged A9M produced a small, not voltage dependent
      block of outward currents. A similar voltage-dependent block by A9C was measured
      both when TMEM16B was activated by 1.5 and 13MUM Ca(2+). However, in the presence
      of 1.5MUM Ca(2+) (but not in 13MUM Ca(2+)), A9C also induced a strong
      potentiation of tail currents measured at -100mV after depolarizing voltages, as
      well as a prolongation of the deactivation kinetics. On the contrary, A9M did not
      produce potentiation of tail currents, showing that the negative charge is
      required for potentiation. Our results provide the first evidence that A9C has
      multiple effects on TMEM16B and that the negative charge of A9C is necessary both
      for voltage-dependent block and for potentiation. Future studies are required to
      identify the molecular mechanisms underlying these complex effects of A9C on
      TMEM16B. Understanding these mechanisms will contribute to the elucidation of the
      structure and functional properties of TMEM16B channels. 

PMID- 25620775
TI  - Unravelling the concept of integrated public health policy: Concept mapping with
      Dutch experts from science, policy, and practice.
AB  - BACKGROUND: While expectations of integrated public health policy (IPHP)
      promoting public health are high, assessment is hampered by the concept's
      ambiguity. This paper aims to contribute to conceptual clarification of IPHP as
      first step in further measurement development. METHODS: In an online concept
      mapping procedure, we invited 237 Dutch experts, 62 of whom generated statements
      on characteristics of IPHP. Next, 100 experts were invited, 24 of whom sorted the
      statements into piles according to their perceived similarity and rated the
      statements on relevance and measurability. Data was analyzed using concept
      mapping software. RESULTS: The concept map consisted of 97 statements, grouped
      into 11 clusters and five themes. Core themes were 'integration', concerning
      'policy coherence' and 'organizing connections', and 'health', concerning
      'positioning health' and 'addressing determinants'. Peripheral themes were
      'generic aspects', 'capacities', and 'goals and setting', which respectively
      addressed general notions of integrated policy making, conditions for IPHP, and
      the variety in manifestations of IPHP. Measurability ratings were low compared to
      relevance. CONCLUSION: The concept map gives an overview of interrelated themes,
      distinguishes core from peripheral dimensions, and provides pointers for theories
      of the policy process. While low measurability ratings indicate measurement
      difficulties, the core themes provide pointers for systematic insight into IPHP
      through measurement.

PMID- 25620776
TI  - Out-of-hours primary care services: demands and patient referral patterns in a
      Veneto region (Italy) Local Health Authority.
AB  - PURPOSE: The aim of this study was to describe the characteristics of patients
      admitted to an out-of-hours (OOH) service and to analyze the related outputs.
      SETTING: A retrospective population-based cohort study was conducted by analyzing
      an electronic database recording 23,980 OOH service contacts in 2011 at a Local
      Health Authority in the Veneto Region (North-East Italy). METHOD: A multinomial
      logistic regression was used to compare the characteristics of contacts handled
      by the OOH physicians with cases referred to other services. RESULTS: OOH service
      contact rates were higher for the oldest and youngest age groups and for females
      rather than males. More than half of the contacts concerned patients who were
      seen by a OOH physician. More than one in three contacts related problems managed
      over the phone; only ~10% of the patients were referred to other services. Many
      factors, including demographic variables, process-logistic variables and clinical
      characteristics of the contact, were associated with the decision to visit the
      patient's home (rather than provide telephone advice alone), or to refer patients
      to an ED or to a specialist. Our study demonstrated, even after adjusting,
      certain OOH physicians were more likely than their colleagues to refer a patient
      to an ED. CONCLUSION: Our study shows that OOH services meet composite and
      variously expressed demands. The determining factors associated with cases
      referred to other health care services should be considered when designing
      clinical pathways in order to ensure a continuity of care. The unwarranted
      variability in OOH physicians' performance needs to be addressed.

PMID- 25620780
TI  - A systematic review of matrix-assisted laser desorption/ionisation time-of-flight
      mass spectrometry compared to routine microbiological methods for the time taken
      to identify microbial organisms from positive blood cultures.
AB  - Bloodstream infections are a significant source of mortality and morbidity.
      Patient outcomes are improved by rapid identification of the causative pathogen
      and administration of appropriate antimicrobial therapy. Matrix-assisted laser
      desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry has recently
      emerged as an alternative to microbiological identification. It is important to
      establish whether the costs of MALDI-TOF are justified by more timely
      identification and appropriate therapy, reduced length of stay and reduced
      hospital costs. We undertook a systematic review of the literature comparing
      MALDI-TOF and routine methods for the identification of the aetiological agent in
      patients with known or suspected bloodstream infection. The primary outcome of
      the review was the 'time to identify' organisms. Information on related measures
      such as 'time to appropriate antimicrobial treatment' and downstream hospital
      cost was also collected where reported. Ten of 775 articles identified met the
      inclusion criteria. All included studies were observational. MALDI-TOF
      identification was at least 24 h faster than routine methods in most
      circumstances. MADLI-TOF was associated with a reduction in downstream hospital
      costs and length of stay in studies reporting these outcomes. The observational
      studies reviewed provide evidence of potentially substantial time savings of
      MALDI-TOF in pathogen identification and instigation of appropriate therapy,
      which may also reduce hospital stay. Due to the small number of studies, all at
      relatively high risk of bias, this cannot be considered as definitive evidence of
      the impact of MALDI-TOF. More and better evidence, including impact on patient
      health and cost-effectiveness, is required. 

PMID- 25620781
TI  - Determination of MICING: a new assay for assessing minimal inhibitory
      concentration for invasive growth.
AB  - Our work was focused on a new assay for characterising clinically important
      yeast. This assay was developed due to the need for new diagnostic methods for
      recognising potentially virulent strains of increasingly important non-albicans
      yeast pathogens, such as Saccharomyces cerevisiae and Candida glabrata. With the
      great diversity among strains for virulence and virulence factors, identification
      to the species level is not sufficient; therefore, testing for specific virulent
      traits remains the best option. We show here that the proposed assay uncovers the
      relationships between the three most important yeast virulence traits in a single
      test: the ability of a strain to invade solid medium, while resisting the
      presence of an antimycotic and high temperature (37  degrees C). We combined the
      quantitative agar invasion assay with classical antimycotic susceptibility
      testing into a single assay. Similarly to the minimal inhibitory concentration
      (MIC) value, we defined the MICING (minimal inhibitory concentration of
      antimycotic for invasive growth) as the concentration of an antimycotic above
      which the yeast invasive growth is significantly repressed. In this study, we
      tested three of the most common antimycotics: fluconazole, itraconazole and
      amphotericin B. The response of yeast strains invasion was characteristic of each
      antimycotic, indicating their mechanisms of action. In addition to MICING, the
      assay provides quantitative information about the superficial and invasive
      growth, and also about the relative invasion, which helps in identifying
      clinically important yeast, such as azole-resistant and/or invasive strains of S.
      cerevisiae and C. glabrata. 

PMID- 25620782
TI  - An algorithm to diagnose influenza infection: evaluating the clinical importance
      and impact on hospital costs of screening with rapid antigen detection tests.
AB  - Rapid antigen detection tests (RADTs) are immunoassays that produce results in 15
      min or less, have low sensitivity (50 %), but high specificity (95 %). We studied
      the clinical impact and laboratory savings of a diagnostic algorithm for
      influenza infection using RADTs as a first-step technique during the influenza
      season. From January 15th to March 31st 2014, we performed a diagnostic algorithm
      for influenza infection consisting of an RADT for all respiratory samples
      received in the laboratory. We studied all the patients with positive results for
      influenza infection, dividing them into two groups: Group A with a negative RADT
      but positive reference tests [reverse transcription polymerase chain reaction (RT
      PCR) and/or culture] and Group B with an initial positive RADT. During the study
      period, we had a total of 1,156 patients with suspicion of influenza infection.
      Of them, 217 (19 %) had a positive result for influenza: 132 (11 %) had an
      initial negative RADT (Group A) and 85 (7 %) had a positive RADT (Group B). When
      comparing patients in Group A and Group B, we found significant differences, as
      follows: prescribed oseltamivir (67 % vs. 82 %; p = 0.02), initiation of
      oseltamivir before 24 h (89 % vs. 97 %; p = 0.03), antibiotics prescribed (89 %
      vs. 67 %; p = <0.01), intensive care unit (ICU) admissions after diagnosis (23 %
      vs. 14 %; p = 0.05), and need for supplementary oxygen (61 % vs. 47 %; p = 0.01).
      An influenza algorithm including RADTs as the first step improves the time of
      administration of proper antiviral therapy, reduces the use of antibiotics and
      ICU admissions, and decreases hospital costs.

PMID- 25620783
TI  - Development of a polyaniline-lignocellulose composite for optimal adsorption of
      Congo red.
AB  - A polyaniline lignocellulose composite (PLC) was synthesized and used in the
      removal of Congo red (CR) from aqueous solution. The adsorption process showed
      good fits to both the pseudo-second-order and pseudo-first-order models and the
      Redlich Peterson isotherm. Boundary layer diffusion was the rate-limiting step.
      The adsorption was spontaneous and endothermic. The combined effect of pH and
      initial dye concentration was antagonistic; the combined effect of initial dye
      concentration and temperature was synergistic, while the combined effect of pH
      and temperature was reciprocal. The maximum CR adsorption capacity of PLC was
      evaluated as 1672.5 mg g(-1). The optimal removal was calculated as 99.85% at pH
      4.29, initial dye concentration of 28.5 mg L(-1) and adsorbent dosage of 0.69 g
      L(-1). The predicted removal capacity showed a good correlation to the
      experimental results. PLC has demonstrated a superior adsorption capacity to many
      other adsorbents reported and could be used as an efficient adsorbent for CR
      removal from industrial wastewater.

PMID- 25620784
TI  - Graphene foam developed with a novel two-step technique for low and high strains
      and pressure-sensing applications.
AB  - Freestanding, mechanically stable, and highly electrically conductive graphene
      foam (GF) is formed with a two-step facile, adaptable, and scalable technique.
      This work also demonstrates the formation of graphene foam with tunable densities
      and its use as strain/pressure sensor for both high and low strains and
      pressures. 

PMID- 25620785
TI  - Power to the people? An international review of the democratizing effects of
      direct elections to healthcare organizations.
AB  - Ensuring that publicly funded health systems are democratically accountable is an
      enduring challenge in policy and practice. One strategy for enhancing public
      officials' accountability is to elect members of the public to oversee their
      performance. Several countries have experimented with direct elections to
      healthcare organizations. The most directly comparable examples involve some
      Canadian regional health authorities, New Zealand district health boards,
      foundation trusts in England and health boards in Scotland. We propose three
      aspects of the process by which the democratizing effects of elections should be
      judged: authorization, accountability and influence. Evidence from these
      countries suggests that the democratization of health systems is a complex task,
      which cannot be completed simply by introducing elections. Copyright (c) 2015
      John Wiley & Sons, Ltd. 

PMID- 25620786
TI  - [Complications associated with plastic meshes and slings. A situation like in the
      US?].
AB  - New surgical strategies have rarely been accepted so rapidly in clinical routine
      worldwide, without available prospective studies proving safety and efficacy.
      After the success of midurethral slings, having been implanted in millions of
      patients, alloplastic meshes are available for the treatment of prolapse with
      new, so far unknown complications in relevant frequency. In the USA with their
      own medicolegal system, there have been a flood of litigations (> 60,000 in
      2014), with compensations of > USD 10 million in individual cases. Even though
      medical strategies and surgical skills might be different in Germany this
      development should encourage strict indications and centralization in pelvic
      floor centers. 

PMID- 25620787
TI  - Infrared-induced variation of the magnetic properties of a magnetoplasmonic film
      with a 3D sub-micron periodic triangular roof-type antireflection structure.
AB  - A carbon-matrix nickel composite magnetoplasmonic film with a 3D sub-micron
      periodic triangular roof-type antireflection structure (SPTAS) was fabricated via
      a simple and promising method that combines chemosynthesis with biomimetic
      techniques. The Troides helena (Linnaeus) forewing (T_FW) was chosen as the
      biomimetic template. The carbon-matrix Ni wing fabricated via electroless Ni
      deposition for 6 h (CNMF_6h) exhibits enhanced infrared absorption. Over a
      wavelength range (888-2500 nm), the enhancement of the infrared absorption of
      CNMF_6h is up to 1.85 times compared with the T_FW. Furthermore, infrared
      excitation induces a photothermal effect that results in variation in the
      magnetic properties of the carbon-matrix Ni wing. The magnetic properties were
      also confirmed using atomic force microscopy (AFM) and magnetic force microscopy
      (MFM). The good correlation between the AFM and MFM images demonstrates that the
      surface of the SPTAS of CNMF_6h exhibits strong magnetic properties. The infrared
      induced photothermal effect that results in magnetic variation is promising for
      use in the design of novel magnetoplasmonic films with potential applications in
      infrared information recording and heat-assisted magnetic recording. 

PMID- 25620788
TI  - Comparison of septal strain patterns in dyssynchronous heart failure between
      speckle tracking echocardiography vendor systems.
AB  - AIM: To analyze inter-vendor differences of speckle tracking echocardiography
      (STE) in imaging cardiac deformation in patients with dyssynchronous heart
      failure. METHODS AND RESULTS: Eleven patients (all with LBBB, median age 60.7
      years, 9 males) with implanted cardiac resynchronization therapy devices were
      prospectively included. Ultrasound systems of two vendors (i.e. General Electric
      and Philips) were used to record images in the apical four chamber view. Regional
      longitudinal strain patterns were analyzed with vendor specific software in the
      basal, mid and apical septal segments. Systolic strain (SS), time to peak strain
      (TTP) and septal rebound stretch (SRS) were determined during four pacing
      settings, resulting in 44 unique strain patterns per segment (total 132
      patterns). Cross correlation was used to analyze the comparability of the shape
      of 132 normalized strain patterns. Correlation of strain patterns of the two
      systems was high (R(2) median: 0.68, interquartile range: 0.53-0.82).
      Accordingly, strain patterns of intrinsic rhythm were recognized equally using
      both systems, when divided into three types. GE based SS (18.9 +/- 4.7%) was
      significantly higher than SS determined by the Philips system (13.4 +/- 4.3%).
      TTP was slightly but non-significantly lower in GE (384 +/- 77 ms) compared to
      Philips (404 +/- 83 ms) derived strain signals. Correlation of SRS between the
      systems was poor, due to minor differences in the strain signal and timing of
      aortic valve closure. CONCLUSIONS: The two systems provide similar shape of
      strain patterns. However, important differences are found in the amplitude,
      timing of systole and SRS. Until STE is standardized, clinical decision making
      should be restricted to pattern analysis.

PMID- 25620789
TI  - The time for naming the Interatrial Block Syndrome: Bayes Syndrome.

PMID- 25620790
TI  - Bipolar disorder: role of immune-inflammatory cytokines, oxidative and
      nitrosative stress and tryptophan catabolites.
AB  - Bipolar disorder (BD) is a complex disorder with a range of presentations. BD is
      defined by the presentation of symptoms of mania or depression, with
      classification dependent on patient/family reports and behavioural observations.
      Recent work has investigated the biological underpinnings of BD, highlighting the
      role played by increased immune-inflammatory activity, which is readily indicated
      by changes in pro-inflammatory cytokines or signalling, both centrally and
      systemically, e.g. increased interleukin-6 trans-signalling. Here, we review the
      recent data on immune-inflammatory pathways and cytokine changes in BD. Such
      changes are intimately linked to changes in oxidative and nitrosative stress
      (O&NS) and neuroregulatory tryptophan catabolites (TRYCATs), both centrally and
      peripherally. TRYCATs take tryptophan away from serotonin, N-acetylserotonin and
      melatonin synthesis, driving it down the TRYCAT pathway, predominantly as a
      result of the pro-inflammatory cytokine induction of indoleamine 2,3-dioxygenase.
      This has led to an emerging biological perspective on the aetiology, course and
      treatment of BD. Such data also better integrates the numerous comorbidities
      associated with BD, including addiction, cardiovascular disorders and increased
      reporting of pain. Immune-inflammatory, O&NS and TRYCAT pathways are also likely
      to be relevant biological underpinnings to the significant decrease in life
      expectancy in BD. 

PMID- 25620791
TI  - Attention bias modification for anxiety and phobias: current status and future
      directions.
AB  - Attention bias modification (ABM) was introduced over a decade ago as a
      computerized method of manipulating attentional bias and has been followed by
      intense interest in applying ABM for clinical purposes. While meta-analyses
      support ABM as a method of modifying attentional biases and reducing anxiety
      symptoms, there have been notable discrepancies in findings published within the
      last several years. In this review, we comment on recent research that may help
      explain some of the inconsistencies across ABM studies. More relevant to the
      future of ABM research, we highlight areas in which continuing research is
      needed. We suggest that ABM appears to be a promising treatment for anxiety
      disorders, but relative to other interventions, ABM is in its infancy. Thus,
      research is needed in order to improve ABM as a clinical treatment and advance
      the psychological science of ABM. 

PMID- 25620794
TI  - Uniaxial compressive behavior of micro-pillars of dental enamel characterized in
      multiple directions.
AB  - In this work, the compressive elastic modulus and failure strength values of
      bovine enamel at the first hierarchical level formed by hydroxyapatite (HA)
      nanofibers and organic matter are identified in longitudinal, transverse and
      oblique direction with the uniaxial micro-compression method. The elastic modulus
      values (~70 GPa) measured here are within the range of results reported in the
      literature but these values were found surprisingly uniform in all orientations
      as opposed to the previous nanoindentation findings revealing anisotropic elastic
      properties in enamel. Failure strengths were recorded up to ~1.7 GPa and
      different failure modes (such as shear, microbuckling, fiber fracture) governed
      by the orientation of the HA nanofibers were visualized. Structural
      irregularities leading to mineral contacts between the nanofibers are postulated
      as the main reason for the high compressive strength and direction-independent
      elastic behavior on enamels first hierarchical level.

PMID- 25620793
TI  - Increased Brain Perfusion Persists over the First Month of Life in Term
      Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated
      Angiogenesis?
AB  - Many asphyxiated newborns still develop brain injury despite hypothermia therapy.
      The development of brain injury in these newborns has been related partly to
      brain perfusion abnormalities. The purposes of this study were to assess brain
      hyperperfusion over the first month of life in term asphyxiated newborns and to
      search for some histopathological clues indicating whether this hyperperfusion
      may be related to activated angiogenesis following asphyxia. In this prospective
      cohort study, regional cerebral blood flow was measured in term asphyxiated
      newborns treated with hypothermia around day 10 of life and around 1 month of
      life using magnetic resonance imaging (MRI) and arterial spin labeling. A total
      of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated
      with hypothermia displayed an increased cerebral blood flow in the injured brain
      areas around day 10 of life and up to 1 month of life. In addition, we looked at
      the histopathological clues in a human asphyxiated newborn and in a rat model of
      neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed
      in the injured brain of an asphyxiated newborn treated with hypothermia in the
      first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and
      the endothelial cell count increased in the injured cortex of the pups 7 and 11
      days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by
      imaging persisted in the injured areas up to 1 month of life and that
      angiogenesis was activated in the injured brain of asphyxiated newborns.

PMID- 25620792
TI  - The lymph node microenvironment and its role in the progression of metastatic
      cancer.
AB  - Lymph nodes are initial sites for cancer metastasis in many solid tumors.
      However, their role in cancer progression is still not completely understood.
      Emerging evidence suggests that the lymph node microenvironment provides
      hospitable soil for the seeding and proliferation of cancer cells. Resident
      immune and stromal cells in the lymph node express and secrete molecules that may
      facilitate the survival of cancer cells in this organ. More comprehensive studies
      are warranted to fully understand the importance of the lymph node in tumor
      progression. Here, we will review the current knowledge of the role of the lymph
      node microenvironment in metastatic progression. 

PMID- 25620797
TI  - NIH's genomic data sharing policy: timing and tradeoffs.
AB  - NIH's new genomic data sharing (GDS) policy covers both human and model-organism
      genotypic and phenotypic data, and strives to balance rapid release of data with
      embargo periods to ensure that data producers have sufficient time to analyze
      their results. But how well does the policy achieve this balance? 

PMID- 25620795
TI  - Antioxidant cerium oxide nanoparticle hydrogels for cellular encapsulation.
AB  - Oxidative stress and the resulting radical by-products cause significant toxicity
      and graft loss in cellular transplantation. Here, the engineering of an auto
      catalytic, antioxidant, self-renewing cerium oxide nanoparticle (CONP)-composite
      hydrogel is reported. This enzyme-mimetic material ubiquitously scavenges ambient
      free radicals, with the potential to provide indefinite antioxidant protection.
      The potential of this system to enhance the protection of encapsulated beta cells
      was evaluated. Co-incubation of CONPs free in solution with beta cells
      demonstrated potent cytoprotection from superoxide exposure; however,
      phagocytosis of the CONPs by the beta cells resulted in cytotoxicity at
      concentrations as low as 1mM. When CONPs were embedded within alginate hydrogels,
      the composite hydrogel provided cytoprotection to encapsulated beta cells from
      free radical attack without cytotoxicity, even up to 10mM. This nanocomposite
      hydrogel has wide applicability in cellular transplantation, with the unique
      advantage of localization of these potent antioxidant CONPs and their capacity
      for sustained, long-term scavenging. 

PMID- 25620798
TI  - Polyvalent immunoglobulins in neonates after perinatal exposure to measles:
      Benefits and long-term tolerance of immunoglobulins.

PMID- 25620796
TI  - Paths to a malaria vaccine illuminated by parasite genomics.
AB  - More human death and disease is caused by malaria parasites than by all other
      eukaryotic pathogens combined. As early as the sequencing of the first human
      genome, malaria parasite genomics was prioritized to fuel the discovery of
      vaccine candidate antigens. This stimulated increased research on malaria,
      generating new understanding of the cellular and molecular mechanisms of
      infection and immunity. This review of recent developments illustrates how new
      approaches in parasite genomics, and increasingly large amounts of data from
      population studies, are helping to identify antigens that are promising lead
      targets. Although these results have been encouraging, effective discovery and
      characterization need to be coupled with more innovation and funding to translate
      findings into newly designed vaccine products for clinical trials. 

PMID- 25620799
TI  - Large cell carcinoma of the lung: a tumor in search of an author. A clinically
      oriented critical reappraisal.
AB  - Large cell carcinoma (LCC) is a merely descriptive term indicating a subtype of
      lung cancer with no specific features of small-cell lung cancer (SCLC),
      adenocarcinoma (ADC) or squamous cell carcinoma (SQC). This diagnosis is allowed
      on surgical specimens only, whereas its counterpart in biopsy/cytology samples is
      non-small-cell lung carcinoma (NSCLC), not otherwise specified (NOS). Although
      these two terms do not fulfill the same concept, they can be interchangeable
      synonyms at the clinical level, reflecting, in different ways, the inability to
      define a specific subtype. Immunohistochemistry (IHC), next generation sequencing
      (NGS) analysis and, historically, electron microscopy have been unveiling diverse
      cell differentiation lineages in LCC, resulting in LCC-favor ADC, LCC-favor SQC
      and LCC-favor large-cell neuroendocrine carcinoma (LCNEC), the latter hopefully
      to be included into the neuroendocrine tumor (NET) group in the future.
      Paradoxically, however, the interpretation issues of LCC/NSCLC-NOS are not
      diminishing, but even increasing albeight an accurate diagnosis is oncologically
      required and crucial. Also, rare LCC/NSCLC-NOS cases exhibiting null/unclear
      phenotype, are difficult to classify, and this terminology could be maintained
      for the sake of classification (basically these tumors are serendipitous ADC, as
      also confirmed by the lack of p40). In this review article, seven relevant issues
      to LCC have been addressed by using a question-answer methodology, with final key
      points discussing major interpretation issues. In conclusion, most LCC/NSCLC-NOS
      may be eventually re-classified and addressed by exploiting IHC and/or molecular
      testing to satisfy the criteria of precision medicine (the right drug, to the
      right patient, at the right time). 

PMID- 25620801
TI  - Work-family boundary strategies: Stability and alignment between preferred and
      enacted boundaries.
AB  - Are individuals bounding work and family the way they would like? Much of the
      work-family boundary literature focuses on whether employees are segmenting or
      integrating work with family, but does not explore the boundaries workers would
      like to have, nor does it examine the fit between desired and enacted boundaries,
      or assess boundary stability. In this study, 23 respondents employed at a large
      Fortune 500 company were interviewed about their work-family boundaries before
      and after their teams underwent a cultural change initiative that sought to
      loosen workplace norms and allow employees more autonomy to decide when and where
      they performed their job tasks. Four distinct boundary strategies emerged from
      the data, with men and parents of young children having better alignment between
      preferred and enacted boundaries than women and those without these caregiving
      duties. Implications for boundary theory and research are discussed.

PMID- 25620802
TI  - Organized Labor and Racial Wage Inequality in the United States.
AB  - Why have African-American private-sector unionization rates surpassed those of
      white workers for decades, and how has private-sector union decline exacerbated
      black-white wage inequality? Using data from the Current Population Survey (1973
      2007), the authors show that African-Americans join unions for protection against
      discriminatory treatment in nonunion sectors. A model-predicted wage series also
      shows that, among women, black-white weekly wage gaps would be between 13% and
      30% lower if union representation remained at high levels. The effect of
      deunionization on racial wage inequality for men is less substantial, but without
      deunionization, weekly wages for black men would be an estimated $49 higher. The
      results recast organized labor as an institution vital for its economic inclusion
      of African-American men and women. This study points to the need to move beyond
      class-based analyses of union decline to an understanding of the gendered role
      unions once played in mitigating racial inequality.

PMID- 25620803
TI  - Immigration, organization, and the Great recession: structural change or
      continuity?

PMID- 25620800
TI  - Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI
      validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol.
AB  - OBJECTIVE: The pathologic validation of European Alzheimer's Disease Consortium
      Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal
      Segmentation Protocol (HarP). METHODS: Temporal lobes of nine Alzheimer's disease
      (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla.
      Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal
      slices were stained for amyloid beta (Abeta), tau, and cresyl violet. Hippocampal
      subfields were manually traced. Neuronal counts, Abeta, and tau burden for each
      hippocampal subfield were obtained. RESULTS: We found significant correlations
      between hippocampal volume and Braak and Braak staging (rho = -0.75, P = .001),
      tau (rho = -0.53, P = .034), Abeta burden (rho = -0.61, P = .012), and neuronal
      count (rho = 0.77, P < .001). Exploratory subfield-wise significant associations
      were found for Abeta in Cornu Ammonis (CA)1 (rho = -0.58, P = .019) and subiculum
      (rho = -0.75, P = .001), tau in CA2 (rho = -0.59, P = .016), and CA3 (rho = -0.5,
      P = .047), and neuronal count in CA1 (rho = 0.55, P = .028), CA3 (rho = 0.65, P =
      .006), and CA4 (rho = 0.76, P = .001). CONCLUSIONS: The observed associations
      provide pathological confirmation of hippocampal morphometry as a valid biomarker
      for AD and pathologic validation of HarP.

PMID- 25620804
TI  - A Paradoxical Result in Estimating Regression Coefficients.
AB  - This paper presents a counterintuitive result regarding the estimation of a
      regression slope co-efficient. Paradoxically, the precision of the slope
      estimator can deteriorate when additional information is used to estimate its
      value. In a randomized experiment, the distribution of baseline variables should
      be identical across treatments due to randomization. The motivation for this
      paper came from noting that the precision of slope estimators deteriorated when
      pooling baseline predictors across treatment groups.

PMID- 25620805
TI  - Declining Use of Wild Resources by Indigenous Peoples of the Ecuadorian Amazon.
AB  - Wild product harvesting by forest-dwelling peoples, including hunting, fishing,
      forest product collection and timber harvesting, is believed to be a major threat
      to the biodiversity of tropical forests worldwide. Despite this threat, few
      studies have attempted to quantify these activities across time or across large
      spatial scales. We use a unique longitudinal household survey (n = 480) to
      describe changes in these activities over time in 32 indigenous communities from
      five ethnicities in the northern Ecuadorian Amazon. To provide insight into the
      drivers of these changes, we also estimate multilevel statistical models of these
      activities as a function of household and community characteristics. These
      analyses reveal that participation in hunting, fishing, and forest product
      collection is high but declining across time and across ethnicities, with no
      evidence for a parallel decline in resource quality. However, participation in
      timber harvesting did not significantly decline and there is evidence of a
      decline in resource quality. Multilevel statistical models additionally reveal
      that household and community characteristics such as ethnicity, demographic
      characteristics, wealth, livelihood diversification, access to forest,
      participation in conservation programs and exposure to external markets are
      significant predictors of wild product harvesting. These characteristics have
      changed over time but cannot account for declining participation in resource
      harvesting. This finding suggests that participation is declining due to changes
      in the regional-scale social and economic context, including urbanization and the
      expansion of government infrastructure and services. The lesson for
      conservationists is that macro-scale social and economic conditions can drive
      reductions in wild product harvesting even in the absence of successful
      conservation interventions.

PMID- 25620806
TI  - Compressive Network Analysis.
AB  - Modern data acquisition routinely produces massive amounts of network data.
      Though many methods and models have been proposed to analyze such data, the
      research of network data is largely disconnected with the classical theory of
      statistical learning and signal processing. In this paper, we present a new
      framework for modeling network data, which connects two seemingly different
      areas: network data analysis and compressed sensing. From a nonparametric
      perspective, we model an observed network using a large dictionary. In
      particular, we consider the network clique detection problem and show connections
      between our formulation with a new algebraic tool, namely Randon basis pursuit in
      homogeneous spaces. Such a connection allows us to identify rigorous recovery
      conditions for clique detection problems. Though this paper is mainly conceptual,
      we also develop practical approximation algorithms for solving empirical problems
      and demonstrate their usefulness on real-world datasets.

PMID- 25620807
TI  - Optimal Feature Selection in High-Dimensional Discriminant Analysis.
AB  - We consider the high-dimensional discriminant analysis problem. For this problem,
      different methods have been proposed and justified by establishing exact
      convergence rates for the classification risk, as well as the l2 convergence
      results to the discriminative rule. However, sharp theoretical analysis for the
      variable selection performance of these procedures have not been established,
      even though model interpretation is of fundamental importance in scientific data
      analysis. This paper bridges the gap by providing sharp sufficient conditions for
      consistent variable selection using the sparse discriminant analysis (Mai et al.,
      2012). Through careful analysis, we establish rates of convergence that are
      significantly faster than the best known results and admit an optimal scaling of
      the sample size n, dimensionality p, and sparsity level s in the high-dimensional
      setting. Sufficient conditions are complemented by the necessary information
      theoretic limits on the variable selection problem in the context of high
      dimensional discriminant analysis. Exploiting a numerical equivalence result, our
      method also establish the optimal results for the ROAD estimator (Fan et al.,
      2012) and the sparse optimal scaling estimator (Clemmensen et al., 2011).
      Furthermore, we analyze an exhaustive search procedure, whose performance serves
      as a benchmark, and show that it is variable selection consistent under weaker
      conditions. Extensive simulations demonstrating the sharpness of the bounds are
      also provided.

PMID- 25620808
TI  - Sparse and Efficient Estimation for Partial Spline Models with Increasing
      Dimension.
AB  - We consider model selection and estimation for partial spline models and propose
      a new regularization method in the context of smoothing splines. The
      regularization method has a simple yet elegant form, consisting of roughness
      penalty on the nonparametric component and shrinkage penalty on the parametric
      components, which can achieve function smoothing and sparse estimation
      simultaneously. We establish the convergence rate and oracle properties of the
      estimator under weak regularity conditions. Remarkably, the estimated parametric
      components are sparse and efficient, and the nonparametric component can be
      estimated with the optimal rate. The procedure also has attractive computational
      properties. Using the representer theory of smoothing splines, we reformulate the
      objective function as a LASSO-type problem, enabling us to use the LARS algorithm
      to compute the solution path. We then extend the procedure to situations when the
      number of predictors increases with the sample size and investigate its
      asymptotic properties in that context. Finite-sample performance is illustrated
      by simulations.

PMID- 25620809
TI  - Can Intensive Early Childhood Intervention Programs Eliminate Income-Based
      Cognitive and Achievement Gaps?
AB  - How much of the income-based gaps in cognitive ability and academic achievement
      could be closed by a two-year, center-based early childhood education
      intervention? Data from the Infant Health and Development Program (IHDP), which
      randomly assigned treatment to low-birth-weight children from both higher- and
      low-income families between ages one and three, shows much larger impacts among
      low-than higher-income children. Projecting IHDP impacts to the U.S. population's
      IQ and achievement trajectories suggests that such a program offered to low
      income children would essentially eliminate the income-based gap at age three and
      between a third and three-quarters of the age five and age eight gaps.

PMID- 25620810
TI  - Family Structure and Child Well-Being: Integrating Family Complexity.
AB  - Although children's family lives are diverse, the measurement of children's
      living arrangements has lagged, focusing on the relationships of children to
      parents while largely ignoring sibling composition. Using data from the 2008
      Survey of Income and Program Participation (N = 23,985) the authors documented
      patterns of family complexity among a nationally representative sample of
      children ages 0-17 living in a range of family structures. They also examined the
      independent and joint associations of family structure and family complexity on
      child economic well-being. Family complexity was independently related to
      economic disadvantage, namely, a lower income-to-needs ratio and a higher
      likelihood of public assistance receipt. The role of family complexity was
      partially contingent on family structure, with the positive association between
      family complexity and receipt of public assistance more pronounced for children
      in families with 2 married biological parents. This study demonstrates the
      utility of integrating family structure and family complexity in studies of
      children's well-being.

PMID- 25620811
TI  - Functionalized Poly(3-hexylthiophene)s via Lithium-Bromine Exchange.
AB  - Poly(3-hexylthiophene) (P3HT) is one of the most extensively investigated
      conjugated polymers and has been employed as the active material in many devices
      including field-effect transistors, organic photovoltaics and sensors. As a
      result, methods to further tune the properties of P3HT are desirable for specific
      applications. Herein, we report a facile postpolymerization modification strategy
      to functionalize the 4-position of commercially available P3HT in two simple
      steps-bromination of the 4-position of P3HT (Br-P3HT) followed by lithium-bromine
      exchange and quenching with an electrophile. We achieved near quantitative
      lithium-bromine exchange with Br-P3HT, which requires over 100 thienyl lithiates
      to be present on a single polymer chain. The lithiated-P3HT is readily combined
      with functional electrophiles, resulting in P3HT derivatives with ketones,
      secondary alcohols, trimethylsilyl (TMS) group, fluorine, or an azide at the 4
      position. We demonstrated that the azide-modified P3HT could undergo Cu-catalyzed
      or Cu-free click chemistry, significantly expanding the complexity of the
      structures that can be appended to P3HT using this method.

PMID- 25620812
TI  - Electrochemical tuning of the activity and structure of a copper-cobalt micro
      nano film on a gold electrode, and its application to the determination of
      glucose and of Chemical Oxygen Demand.
AB  - Micro-nano structured Cu-Co was in situ fabricated on the surface of a gold
      electrode via electrochemical reduction of CuCl2 and Co(NO3)2. It is shown that
      the shape of the particles can be controlled by variation of deposition current,
      deposition time, pH value and the ratio of Cu(II) and Co(II) ions. If prepared
      under current of -200 MUA in 0.1 M, pH 4.0 acetate buffer solution, the film
      possesses high catalytic activity towards the electrochemical oxidation of
      glucose at a largely increased oxidation current compared to a non-modified
      surface. The electrochemical activity of this sensor can be easily tuned. Glucose
      is a standard compound for evaluating the chemical oxygen demand (COD), and we
      have therefore studied the application of the sensor to the determination of this
      parameter. Under optimized conditions, the sensor has linear response to glucose
      in the 1.92-768 mg L-1 concentration range, and the detection limit is 0.609 mg L
      1 (at an S/N ratio of 3). A large number of surface water samples was studied,
      and the results obtained by this method were found to be linearly correlated to
      those obtained by the dichromate method (r = 0.995; n = 33). Graphical
      AbstractThis study describes the facile synthesis of micro-nano Cu-Co by one-step
      electrodeposition of Cu(II) and Co(II) on gold electrode. The alloy composite
      exhibited excellent electrocatalytic activities, and was successfully applied on
      the COD determination of glucose and water samples.

PMID- 25620813
TI  - CROSS-LINKED POLYMER MICELLES WITH BIODEGRADABLE IONIC CORES FOR ANTI-CANCER DRUG
      DELIVERY.

PMID- 25620814
TI  - Predicting time to threshold for initiating antiretroviral treatment to evaluate
      cost of treatment as HIV prevention.
AB  - The goal of this paper is to predict the additional amount of antiretroviral
      treatment that would be required to implement a policy of treating all HIV
      infected people at time of detection of infection rather than at the time that
      their CD4 T-lymphocyte counts are observed to be below a threshold-the current
      standard of care. We describe a sampling-based inverse prediction method for
      predicting time from HIV infection to attainment of the CD4 threshold and apply
      it to a set of treatment-naive HIV-infected subjects in a village in Botswana who
      participated in a household survey that collected cross-sectional CD4 counts. The
      inferential target of interest is the population-level mean time to reaching CD4
      based treatment threshold in this group of subjects. To address the challenges
      arising from the fact that these subject's dates of HIV infection are unknown, we
      make use of data from an auxiliary cohort study of subjects enrolled shortly
      after HIV infection in which CD4 counts were measured over time. We use a
      multiple imputation framework to combine across the different sources of data,
      and discuss how the methods compensate for the length-biased sampling inherent in
      cross-sectional screening procedures, such as household surveys. We comment on
      how the results bear upon analyses of costs of implementation of treatment-for
      prevention use of antiretroviral drugs in HIV prevention interventions.

PMID- 25620815
TI  - Co-resident Grandparents and Grandchildren's Academic Performance in Taiwan.
AB  - Using the Taiwanese panel survey data, we investigate the consequences of
      children's co-residence with grandparents, and we find a positive effect on
      academic achievement. Further analysis reveals different types of effects among
      the various types of grandparent-grandchild co-residence. While long-term co
      residence confers the most educational benefits, a recent transition into co
      residence confers no such advantage. Compared to other co-resident situations,
      children who recently transition out of co-residence with grandparents are the
      most disadvantaged. Furthermore, we find educational benefits of co-resident
      grandparents in both single-parent and two-parent families, but long-term co
      resident grandparents' positive association with grandchildren's academic
      achievement is the most pronounced in households where both parents are absent.
      We interpret these finding using a theoretical framework, and discuss their
      implications for policy and for other research.

PMID- 25620817
TI  - Accurate Critical Stress Intensity Factor Griffith Crack Theory Measurements by
      Numerical Techniques.
AB  - Critical stress intensity factor (KIc) has been an approximation for fracture
      toughness using only load-cell measurements. However, artificial man-made cracks
      several orders of magnitude longer and wider than natural flaws have required a
      correction factor term (Y) that can be up to about 3 times the recorded
      experimental value [1-3]. In fact, over 30 years ago a National Academy of
      Sciences advisory board stated that empirical KIc testing was of serious concern
      and further requested that an accurate bulk fracture toughness method be found
      [4]. Now that fracture toughness can be calculated accurately by numerical
      integration from the load/deflection curve as resilience, work of fracture (WOF)
      and strain energy release (SIc) [5, 6], KIc appears to be unnecessary. However,
      the large body of previous KIc experimental test results found in the literature
      offer the opportunity for continued meta analysis with other more practical and
      accurate fracture toughness results using energy methods and numerical
      integration. Therefore, KIc is derived from the classical Griffith Crack Theory
      [6] to include SIc as a more accurate term for strain energy release rate (??Ic),
      along with crack surface energy (gamma), crack length (a), modulus (E), applied
      stress (sigma), Y, crack-tip plastic zone defect region (rp) and yield strength
      (sigmays) that can all be determined from load and deflection data. Polymer
      matrix discontinuous quartz fiber-reinforced composites to accentuate toughness
      differences were prepared for flexural mechanical testing comprising of 3 mm
      fibers at different volume percentages from 0-54.0 vol% and at 28.2 vol% with
      different fiber lengths from 0.0-6.0 mm. Results provided a new correction factor
      and regression analyses between several numerical integration fracture toughness
      test methods to support KIc results. Further, bulk KIc accurate experimental
      values are compared with empirical test results found in literature. Also,
      several fracture toughness mechanisms are discussed especially for fiber
      reinforced composites.

PMID- 25620816
TI  - Neuropsychiatric Symptoms in Lupus.

PMID- 25620818
TI  - China's New Demographic Reality: Learning from the 2010 Census.
AB  - The paper provides an examination of China's 2010 census data to evaluate its
      quality and to assess China's demographic situation. The demographic trends
      revealed by the new census data suggest that China has entered a new demographic
      era characterized by prolonged low fertility, elevated sex ratios, rapid aging,
      fast urbanization and major geographic redistribution. How China responses to
      these demographic challenges will have profound implications for its social and
      economic future.

PMID- 25620819
TI  - Very Early Language Skills of Fifth-Grade Poor Comprehenders.
AB  - This study tested the theory that future poor comprehenders would show modest but
      pervasive deficits in both language comprehension and production during early
      childhood as compared with future poor decoders and typical readers. Using an
      existing database (NICHD ECCRN), fifth-grade students were identified as having
      poor comprehension skills (n = 516), poor decoding skills (n = 511) or typical
      reading skills (n = 535) based on standardized assessments of word recognition
      and reading comprehension. Language comprehension and production during the
      toddler and preschool years were retrospectively compared across these subgroups.
      Compared with future typical readers and poor decoders, poor comprehenders had
      the lowest abilities on language assessments at 15, 24, 36 and 54 months. For
      nearly all contrasts, the difference between poor comprehenders and the other
      groups of readers exceeded .5 standard deviation in magnitude, indicating that
      the early language skills of poor comprehenders exhibit appreciable lags.

PMID- 25620820
TI  - Productive Vocabulary among Three Groups of Bilingual American Children:
      Comparison and Prediction.
AB  - The importance of input factors for bilingual children's vocabulary development
      was investigated. Forty-seven Argentine, 42 South Korean, 51 European American,
      29 Latino immigrant, 26 Japanese immigrant, and 35 Korean immigrant mothers
      completed checklists of their 20-month-old children's productive vocabularies.
      Bilingual children's vocabulary sizes in each language separately were
      consistently smaller than their monolingual peers but only Latino bilingual
      children had smaller total vocabularies than monolingual children. Bilingual
      children's vocabulary sizes were similar to each other. Maternal acculturation
      predicted the amount of input in each language, which then predicted children's
      vocabulary size in each language. Maternal acculturation also predicted
      children's English-language vocabulary size directly.

PMID- 25620821
TI  - The determinants of receiving social care in later life in England.
AB  - Demographic change and policy changes in social care provision can affect the
      type of social care support received by older people, whether through informal,
      formal state or formal paid-for sources. This paper analyses the English
      Longitudinal Study of Ageing data (wave 4) in order to examine the relationship
      between demographic and socio-economic characteristics, and the receipt of
      support from different sources by older people who report difficulty with daily
      activities. The research outlines three key results with implications for the
      future organisation of social care for older people. Firstly, the number of
      instrumental activities of daily living (IADLs) an older person reports having
      difficulty with, followed by the number of activities of daily living (ADLs) are
      the strongest determinants of receiving support from any source. Secondly, there
      are significant gender differences in the factors associated with receiving
      support from different sources; for example, physical health is a strong
      determinant of informal support receipt by men, while mental health status is a
      strong determinant of informal support receipt by women. Finally, the research
      shows that different kinds of impediments in everyday life are associated with
      receiving support from different sources. This 'link' between particular types of
      difficulties and support receipt from particular sources raises questions about
      the way social care provision can or should be organised in the future.

PMID- 25620822
TI  - Lectin and antibody-based histochemical techniques for cardiovascular tissue
      engineering.
AB  - Tissue engineering holds immense potential for treatment of cardiovascular
      diseases by creating living structures to replace diseased blood vessels, heart
      valves, and cardiac muscle. In a traditional approach, scaffolds are seeded with
      stem cells and subjected to stimuli in bioreactors that mimic physiologic
      conditions or are directly implanted into target sites in animal models. The
      expected results are significant cell changes, extensive remodeling of the
      scaffolds and creation of surrogate structures that would be deemed acceptable
      for tissue regeneration. Histochemical techniques are increasingly becoming
      essential tools in tissue engineering research. In our studies, we used lectin
      and antibody-based techniques to characterize novel collagen and elastin
      scaffolds and to ensure efficient removal of xenoantigens. Scaffolds were
      implanted in animals and infiltrated host cells were identified using antibodies
      to activated fibroblasts, macrophages, and lymphocytes. Stem cell-seeded
      scaffolds were subjected to mechanical strains and tested for differentiation
      into cardiovascular cells using antibody-based double immunofluorescence methods.
      Finally, living heart valves were constructed from scaffolds and stem cells,
      subjected to conditioning in a bioreactor and stem cell differentiation evaluated
      by immunofluorescence. Overall, these techniques have proven to be outstanding
      companions to biochemical, molecular biology and cell analysis methods used in
      tissue engineering research and development.

PMID- 25620823
TI  - A simple cost-effective modification improves the quality of immunocytochemical
      staining in cervical scrape samples characterized by presence of excess mucus.
AB  - Immunocytochemistry (ICC) is a very important tool in a diverse range of
      biomedical research as well as in diagnostic cytopathology. Smears prepared from
      cervical scrapes contain a large amount of overlying mucus that interferes with
      the standard immunocytochemical staining protocol. A modified ICC protocol is
      described, which involves pretreatment of these smears with 1 mg/ml solution of
      Ambroxol hydrochloride in methanol for 1 hour. Source of Ambroxol hydrochloride
      was a 30 mg MucoliteTM tablet, at a cost of 1.70 rupees (~3.5 US cents) per
      tablet. This mucolytic solution effectively clears the mucus, facilitating the
      accessibility of the antibody to the antigenic determinants. This pretreatment
      resulted in the increased percentage of positively stained cells as well as
      staining intensity, leading to improved overall ICC staining and score. This is a
      novel modification that can be cost-effectively applied in ICC staining protocols
      for cytology samples characterized by the presence of excess mucus.

PMID- 25620824
TI  - A Multiresolution Hazard Model for Multicenter Survival Studies: Application to
      Tamoxifen Treatment in Early Stage Breast Cancer.
AB  - In multicenter studies, one often needs to make inference about a population
      survival curve based on multiple, possibly heterogeneous survival data from
      individual centers. We investigate a flexible Bayesian method for estimating a
      population survival curve based on a semiparametric multiresolution hazard model
      that can incorporate covariates and account for center heterogeneity. The method
      yields a smooth estimate of the survival curve for "multiple resolutions" or time
      scales of interest. The Bayesian model used has the capability to accommodate
      general forms of censoring and a priori smoothness assumptions. We develop a
      model checking and diagnostic technique based on the posterior predictive
      distribution and use it to identify departures from the model assumptions. The
      hazard estimator is used to analyze data from 110 centers that participated in a
      multicenter randomized clinical trial to evaluate tamoxifen in the treatment of
      early stage breast cancer. Of particular interest are the estimates of center
      heterogeneity in the baseline hazard curves and in the treatment effects, after
      adjustment for a few key clinical covariates. Our analysis suggests that the
      treatment effect estimates are rather robust, even for a collection of small
      trial centers, despite variations in center characteristics.

PMID- 25620825
TI  - Exact meta-analysis approach for discrete data and its application to 2 * 2
      tables with rare events.
AB  - This paper proposes a general exact meta-analysis approach for synthesizing
      inferences from multiple studies of discrete data. The approach combines the p
      value functions (also known as significance functions) associated with the exact
      tests from individual studies. It encompasses a broad class of exact meta
      analysis methods, as it permits broad choices for the combining elements, such as
      tests used in individual studies, and any parameter of interest. The approach
      yields statements that explicitly account for the impact of individual studies on
      the overall inference, in terms of efficiency/power and the type I error rate.
      Those statements also give rises to empirical methods for further enhancing the
      combined inference. Although the proposed approach is for general discrete
      settings, for convenience, it is illustrated throughout using the setting of meta
      analysis of multiple 2 * 2 tables. In the context of rare events data, such as
      observing few, zero or zero total (i.e., zero events in both arms) outcomes in
      binomial trials or 2 * 2 tables, most existing meta-analysis methods rely on the
      large-sample approximations which may yield invalid inference. The commonly used
      corrections to zero outcomes in rare events data, aiming to improve numerical
      performance can also incur undesirable consequences. The proposed approach
      applies readily to any rare event setting, including even the zero total event
      studies without any artificial correction. While debates continue on whether or
      how zero total event studies should be incorporated in meta-analysis, the
      proposed approach has the advantage of automatically including those studies and
      thus making use of all available data. Through numerical studies in rare events
      settings, the proposed exact approach is shown to be efficient and, generally,
      outperform commonly used meta-analysis methods, including Mental-Haenszel and
      Peto methods.

PMID- 25620826
TI  - Is Smoking Behavior Culturally Determined? Evidence from British Immigrants.
AB  - We exploit migration patterns from the UK to Australia and the US to investigate
      whether a person's decision to smoke is determined by culture. For each country,
      we use retrospective data to describe individual smoking trajectories over the
      life-course. For the UK, we use these trajectories to measure culture by cohort
      and cohort-age, and more accurately relative to the extant literature. Our proxy
      predicts smoking participation of second-generation British immigrants but not
      that of non-British immigrants and natives. Researchers can apply our strategy to
      estimate culture effects on other outcomes when retrospective or longitudinal
      data are available.

PMID- 25620827
TI  - GEE type inference for clustered zero-inflated negative binomial regression with
      application to dental caries.
AB  - Use of zero-inflated count data models is common in applications where the number
      of zero counts exceeds that predicted from a traditional count data model such as
      Poisson or negative binomial. When count data exhibiting inflated zero counts are
      correlated among subjects, a natural approach will be to fit a marginal model
      with the help of generalized estimating equations (GEE) that can incorporate
      subject-to-subject correlations. A GEE based zero-inflated negative binomial
      (ZINB) model is proposed to fit clustered counts with excessive zeros. However,
      the corresponding sandwich variance estimator appears to underestimate the true
      variance. The theoretical reasons for its failure are explained and a correction
      under additional modeling assumptions is offered. In addition, a clustered
      resampling (bootstrap) procedure is proposed to estimate the variance and it is
      shown that the bootstrap procedure captures the correct variance under no
      additional model assumptions. Utility of this marginal GEE based ZINB model over
      two other competing models has been assessed using a thorough simulation study.
      The resulting inference procedure is applied to study the association between the
      dental caries and fluoride exposures using a dataset extracted from the Iowa
      Fluoride Study. A number of risk factors of clinical significance are reliably
      identified using the proposed model.

PMID- 25620828
TI  - Generic language and judgements about category membership: Can generics highlight
      properties as central?
AB  - Many languages distinguish generic utterances (e.g., "Tigers are ferocious") from
      non-generic utterances (e.g., "Those tigers are ferocious"). Two studies examined
      how generic language specially links properties and categories. We used a novel
      word extension task to ask if 4- to 5-year-old children and adults distinguish
      between generic and specific language, and judge that predicating a property of a
      depicted novel animal using generic language (e.g., "Bants have stripes"), rather
      than non-generic language (e.g., "This bant has stripes") implies a more kind
      relevant connection between category and property. Participants were asked to
      endorse an extension of the label taught to a novel animal matching the target
      instance on either overall similarity or the mentioned property. Wording was
      found to have a significant effect on responses for both age groups. Altogether,
      the results of these studies suggest that the generic may be a default
      interpretation for young children, who need to learn the semantics of specific
      and set-theoretic expressions.

PMID- 25620829
TI  - Forms of Friendship: A Person-Centered Assessment of the Quality, Stability, and
      Outcomes of Different Types of Adolescent Friends.
AB  - Friendships differ in terms of their quality and participants may or may not
      agree as to their perceptions of relationship quality. Two studies (N = 230 and
      242) were conducted to identify distinct and replicable categories of friendship
      among young adolescents (M = 11.6 years old) using self and partner reports of
      relationship quality. Same-sex friendships were identified from reciprocated
      friend nominations. Each friend described perceptions of negativity and social
      support in the relationship. Cluster analyses based on reports from both friends
      yielded 4 friendship types in each study: a high quality group, a low quality
      group, and two groups in which friends disagreed about the quality of the
      relationship. High quality friendships were most apt to be stable from the 6th to
      the 7th grade. Participants in high quality friendships reported the highest
      levels of global self-worth and perceived behavioral conduct and the lowest
      levels of problem behaviors. Dyads reporting discrepant perceptions of quality
      differed from dyads who agreed that the friendship was high quality in terms of
      stability and individual adjustment, underscoring the advantages of person
      centered strategies that incorporate perceptions of both partners in
      categorizations of relationships.

PMID- 25620830
TI  - One-Year Test-Retest Reliability of the Maryland Resource for the Behavioral
      Utilization of the Reinforcement of Negative Stimuli (MRBURNS).
AB  - The Maryland Resource for the Behavioral Utilization of the Reinforcement of
      Negative Stimuli (MRBURNS) is a novel behavioral task designed to measure
      individual differences in negative reinforcement-based risk taking propensity.
      Performance on the MRBURNS has been linked with alcohol-related problems and
      negative reinforcement-based drinking motives, as well as symptoms of anxiety and
      depression; however, it is unclear if performance on the task represents a stable
      measure of negative reinforcement-based risk taking over time. As such, the
      current study aimed to examine the test-retest reliability of the MRBURNS over a
      period of one year. Results indicate that the correlation between year 1 and year
      2 risk behavior (average number of pumps) on the MRBURNS was .43 across all
      trials. With the one year test-retest reliability of the MRBURNS established, the
      MRBURNS may be a useful approach to measuring the relative contribution of
      negative reinforcement-based risk taking in the development of risky behaviors
      over time, and may be used to monitor the effects of novel interventions that aim
      to reduce negative reinforcement based risk taking in the real world.

PMID- 25620831
TI  - Fatherhood and Men's Lives at Middle Age.
AB  - This paper uses data on 2,024 men who were followed through the third wave of the
      National Survey of Families and Households to examine the implications of
      fatherhood experiences for men's involvement in altruistic social activities at
      middle age. We find that middle-aged men (ages 45-65) who at some point in their
      lives become fathers are significantly more likely to have altruistically
      oriented social relationships and be involved in service organizations compared
      to men who have never become fathers. Furthermore, it appears that the defining
      aspect of the effect of fatherhood is the level of engagement with children while
      they are growing up. Neither current residential status nor whether current non
      residence occurs because of nest leaving is found to distinguish men's altruistic
      ties.

PMID- 25620832
TI  - Pictorial approaches for measuring time use in rural Ethiopia.
AB  - Time use researchers working in least developed countries (LDCs) face
      difficulties collecting data from illiterate populations who may conceptualize
      time differently than those in industrialized countries. We identify existing
      gaps in time use data collection methods and discuss two novel, pictorial methods
      to collect time use data from these populations. The first method is a modified
      recall interview modeled on participatory rural appraisal (PRA) methods that asks
      respondents to place macaroni on pictures of activity categories in proportion to
      the amount of time spent on that activity during the previous day. The second is
      a simplified pictorial time diary that uses a timer and sequentially-numbered
      stickers to re-create the temporal order of activities in 30-minute increments.
      The latter method also avoids recall bias problems. We present time use data
      collected in 2009 using these methods in a study examining the impacts of water
      infrastructure on women and children's time use in rural Ethiopia. In total, we
      collected information using the first method from 263 household members over age
      10, including 167 water collectors, and pilot-tested the pictorial diary approach
      with 10 adult respondents.

PMID- 25620833
TI  - Fish swimming in schools save energy regardless of their spatial position.
AB  - For animals, being a member of a group provides various advantages, such as
      reduced vulnerability to predators, increased foraging opportunities and reduced
      energetic costs of locomotion. In moving groups such as fish schools, there are
      benefits of group membership for trailing individuals, who can reduce the cost of
      movement by exploiting the flow patterns generated by the individuals swimming
      ahead of them. However, whether positions relative to the closest neighbours
      (e.g. ahead, sided by side or behind) modulate the individual energetic cost of
      swimming is still unknown. Here, we addressed these questions in grey mullet Liza
      aurata by measuring tail-beat frequency and amplitude of 15 focal fish, swimming
      in separate schools, while swimming in isolation and in various positions
      relative to their closest neighbours, at three speeds. Our results demonstrate
      that, in a fish school, individuals in any position have reduced costs of
      swimming, compared to when they swim at the same speed but alone. Although fish
      swimming behind their neighbours save the most energy, even fish swimming ahead
      of their nearest neighbour were able to gain a net energetic benefit over
      swimming in isolation, including those swimming at the front of a school.
      Interestingly, this energetic saving was greatest at the lowest swimming speed
      measured in our study. Because any member of a school gains an energetic benefit
      compared to swimming alone, we suggest that the benefits of membership in moving
      groups may be more strongly linked to reducing the costs of locomotion than
      previously appreciated.

PMID- 25620834
TI  - Appetite for self-destruction: suicidal biting as a nest defense strategy in
      Trigona stingless bees.
AB  - Self-sacrificial behavior represents an extreme and relatively uncommon form of
      altruism in worker insects. It can occur, however, when inclusive fitness
      benefits are high, such as when defending the nest. We studied nest defense
      behaviors in stingless bees, which live in eusocial colonies subject to
      predation. We introduced a target flag to nest entrances to elicit defensive
      responses and quantified four measures of defensivity in 12 stingless bee species
      in Sao Paulo State, Brazil. These included three Trigona species, which are
      locally known for their aggression. Species varied significantly in their attack
      probability (cross species range = 0-1, P < 0.001), attack latency (7.0-23.5 s, P
      = 0.002), biting duration of individual bees (3.5-508.7 s, P < 0.001), and number
      of attackers (1.0-10.8, P < 0.001). A "suicide" bioassay on the six most
      aggressive species determined the proportion of workers willing to suffer fatal
      damage rather than disengage from an intruder. All six species had at least some
      suicidal individuals (7-83 %, P < 0.001), reaching 83 % in Trigona hyalinata.
      Biting pain was positively correlated with an index of overall aggression (P =
      0.002). Microscopic examination revealed that all three Trigona species had five
      sharp teeth per mandible, a possible defensive adaptation and cause of increased
      pain. Suicidal defense via biting is a new example of self-sacrificial altruism
      and has both parallels and differences with other self-sacrificial worker
      insects, such as the honey bee. Our results indicate that suicidal biting may be
      a widespread defense strategy in stingless bees, but it is not universal.

PMID- 25620835
TI  - The costs of parental and mating effort for male baboons.
AB  - Sexual selection theory predicts that males in polygynous species of mammals will
      invest more reproductive effort in mate competition than parental investment. A
      corollary to this prediction is that males will mount a stress response when
      their access to mates is threatened. Indeed, numerous studies have shown that
      males exhibit elevated stress hormones, or glucocorticoids (GCs), when their
      access to females, or a proxy to this access like dominance rank, is challenged.
      In contrast, the relationship between stress hormones and paternal effort is less
      obvious. We report results from a study of wild male chacma baboons indicating
      that males experienced elevated GC levels during periods of social instability
      following the immigration of a dominant male. These effects were strongest in
      males whose mating opportunities were at greatest risk: high-ranking males and
      males engaged in sexual consortships. Males involved in friendships with
      lactating females, a form of paternal investment, also experienced high GC levels
      during these periods of instability. There was a tendency for males with
      lactating female friends to reduce their time spent in consortships during
      unstable periods, when the risk of infanticide was high. Thus, even in a highly
      polygynous mammal, males may have to balance paternal effort with mating effort.
      Males who invest entirely in mating effort risk losing the infants they have
      sired to infanticide. Males who invest in paternal care may enhance their
      offspring's survival, but at the cost of elevated GC levels, the risk of injury,
      and the loss of mating opportunities.

PMID- 25620836
TI  - Fagaceae pollen from the early Cenozoic of West Greenland: revisiting Engler's
      and Chaney's Arcto-Tertiary hypotheses.
AB  - In this paper we document Fagaceae pollen from the Eocene of western Greenland.
      The pollen record suggests a remarkable diversity of the family in the early
      Cenozoic of Greenland. Extinct Fagaceae pollen types include Eotrigonobalanus,
      which extends at least back to the Paleocene, and two ancestral pollen types with
      affinities to the Eurasian Quercus Group Ilex and the western North American
      Quercus Group Protobalanus. In addition, modern lineages of Fagaceae are
      unambiguously represented by pollen of Fagus, Quercus Group Lobatae/Quercus, and
      three Castaneoideae pollen types. These findings corroborate earlier findings
      from Axel Heiberg Island that Fagaceae were a dominant element at high latitudes
      during the early Cenozoic. Comparison with coeval or older mid-latitude records
      of modern lineages of Fagaceae shows that modern lineages found in western
      Greenland and Axel Heiberg likely originated at lower latitudes. Further examples
      comprise (possibly) Acer, Aesculus, Alnus, Ulmus, and others. Thus, before
      fossils belonging to modern northern temperate lineages will have been recovered
      from older (early Eocene, Paleocene) strata from high latitudes, Engler's
      hypothesis of an Arctic origin of the modern temperate woody flora of Eurasia,
      termed 'Arcto-Tertiary Element', and later modification by R. W. Chaney and H. D.
      Mai ('Arcto-Tertiary Geoflora') needs to be modified.

PMID- 25620837
TI  - Remnants of the Legume Ancestral Genome Preserved in Gene-Rich Regions: Insights
      from Lupinus angustifolius Physical, Genetic, and Comparative Mapping.
AB  - The narrow-leafed lupin (Lupinus angustifolius) was recently considered as a
      legume reference species. Genetic resources have been developed, including a
      draft genome sequence, linkage maps, nuclear DNA libraries, and cytogenetic
      chromosome-specific landmarks. Here, we used a complex approach, involving DNA
      fingerprinting, sequencing, genetic mapping, and molecular cytogenetics, to
      localize and analyze L. angustifolius gene-rich regions (GRRs). A L.
      angustifolius genomic bacterial artificial chromosome (BAC) library was screened
      with short sequence repeat (SSR)-based probes. Selected BACs were fingerprinted
      and assembled into contigs. BAC-end sequence (BES) annotation allowed us to
      choose clones for sequencing, targeting GRRs. Additionally, BESs were aligned to
      the scaffolds of the genome sequence. The genetic map was supplemented with 35
      BES-derived markers, distributed in 14 linkage groups and tagging 37 scaffolds.
      The identified GRRs had an average gene density of 19.6 genes/100 kb and physical
      to-genetic distance ratios of 11 to 109 kb/cM. Physical and genetic mapping was
      supported by multi-BAC-fluorescence in situ hybridization (FISH), and five new
      linkage groups were assigned to the chromosomes. Syntenic links to the genome
      sequences of five legume species (Medicago truncatula, Glycine max, Lotus
      japonicus, Phaseolus vulgaris, and Cajanus cajan) were identified. The
      comparative mapping of the two largest lupin GRRs provides novel evidence for
      ancient duplications in all of the studied species. These regions are conserved
      among representatives of the main clades of Papilionoideae. Furthermore, despite
      the complex evolution of legumes, some segments of the nuclear genome were not
      substantially modified and retained their quasi-ancestral structures. Cytogenetic
      markers anchored in these regions constitute a platform for heterologous mapping
      of legume genomes.

PMID- 25620838
TI  - The Rural Context of Illicit Substance Offers: A Study of Appalachian Rural
      Adolescents.
AB  - Rural adolescents are at risk for early initiation and problematic substance use,
      but to date few studies have examined the rural context of substance use. To
      better understand substance offers in the rural context, semi-structured
      interviews were conducted with 118, 12-19 year old adolescents (M = 13.68, SD =
      1.37) from Appalachian, rural school districts in Pennsylvania and Ohio.
      Interviews elicited stories about substance offer-response episodes including
      where offers occurred, who offered substances, and how youth gained access to
      illicit substances. Findings describe the settings in which substance offers and
      use occur for these rural adolescents and advance prevention efforts for
      tailoring health messages to this target population.

PMID- 25620839
TI  - Synthesis of pyridine derivatives as potential antagonists of chemokine receptor
      type 4.
AB  - A series of pyridine derivatives were synthesized as potential inhibitors of
      chemokine receptor type 4. This chemokine receptor has been linked to various
      disease pathways including HIV-1 proliferation, autoimmune disorders,
      inflammatory diseases, and cancer metastasis. The compounds were tested for
      activity using an affinity binding assay and an assay that tests the ability to
      inhibit cell invasion. Two hit compounds (2b and 2j) have been identified for
      further evaluation that inhibit cell invasion by at least 50% and have an
      effective concentration of less than 100 nM in the binding affinity assay. The
      structures of the synthesized compounds were confirmed by spectral data.

PMID- 25620840
TI  - Q- and A-learning Methods for Estimating Optimal Dynamic Treatment Regimes.
AB  - In clinical practice, physicians make a series of treatment decisions over the
      course of a patient's disease based on his/her baseline and evolving
      characteristics. A dynamic treatment regime is a set of sequential decision rules
      that operationalizes this process. Each rule corresponds to a decision point and
      dictates the next treatment action based on the accrued information. Using
      existing data, a key goal is estimating the optimal regime, that, if followed by
      the patient population, would yield the most favorable outcome on average. Q- and
      A-learning are two main approaches for this purpose. We provide a detailed
      account of these methods, study their performance, and illustrate them using data
      from a depression study.

PMID- 25620841
TI  - Interference and Sensitivity Analysis.
AB  - Causal inference with interference is a rapidly growing area. The literature has
      begun to relax the "no-interference" assumption that the treatment received by
      one individual does not affect the outcomes of other individuals. In this paper
      we briefly review the literature on causal inference in the presence of
      interference when treatments have been randomized. We then consider settings in
      which causal effects in the presence of interference are not identified, either
      because randomization alone does not suffice for identification, or because
      treatment is not randomized and there may be unmeasured confounders of the
      treatment-outcome relationship. We develop sensitivity analysis techniques for
      these settings. We describe several sensitivity analysis techniques for the
      infectiousness effect which, in a vaccine trial, captures the effect of the
      vaccine of one person on protecting a second person from infection even if the
      first is infected. We also develop two sensitivity analysis techniques for causal
      effects in the presence of unmeasured confounding which generalize analogous
      techniques when interference is absent. These two techniques for unmeasured
      confounding are compared and contrasted.

PMID- 25620842
TI  - Connecting micro dynamics and population distributions in system dynamics models.
AB  - Researchers use system dynamics models to capture the mean behavior of groups of
      indistinguishable population elements (e.g., people) aggregated in stock
      variables. Yet, many modeling problems require capturing the heterogeneity across
      elements with respect to some attribute(s) (e.g., body weight). This paper
      presents a new method to connect the micro-level dynamics associated with
      elements in a population with the macro-level population distribution along an
      attribute of interest without the need to explicitly model every element. We
      apply the proposed method to model the distribution of Body Mass Index and its
      changes over time in a sample population of American women obtained from the U.S.
      National Health and Nutrition Examination Survey. Comparing the results with
      those obtained from an individual-based model that captures the same phenomena
      shows that our proposed method delivers accurate results with less computation
      than the individual-based model.

PMID- 25620843
TI  - Public and health professionals' misconceptions about the dynamics of body weight
      gain/loss.
AB  - Human body energy storage operates as a stock-and-flow system with inflow (food
      intake) and outflow (energy expenditure). In spite of the ubiquity of stock-and
      flow structures, evidence suggests that human beings fail to understand stock
      accumulation and rates of change, a difficulty called the stock-flow failure.
      This study examines the influence of health care training and cultural background
      in overcoming stock-flow failure. A standardized protocol assessed lay people's
      and health care professionals' ability to apply stock-and-flow reasoning to infer
      the dynamics of weight gain/loss during the holiday season (621 subjects from
      seven countries). Our results indicate that both types of subjects exhibited
      systematic errors indicative of use of erroneous heuristics. Stock-flow failure
      was found across cultures and was not improved by professional health training.
      The problem of stock-flow failure as a transcultural global issue with education
      and policy implications is discussed.

PMID- 25620844
TI  - ESTIMATING PERSON-CENTERED TREATMENT (PeT) EFFECTS USING INSTRUMENTAL VARIABLES:
      AN APPLICATION TO EVALUATING PROSTATE CANCER TREATMENTS.
AB  - This paper builds on the methods of local instrumental variables developed by
      Heckman and Vytlacil (1999, 2001, 2005) to estimate person-centered treatment
      (PeT) effects that are conditioned on the person's observed characteristics and
      averaged over the potential conditional distribution of unobserved
      characteristics that lead them to their observed treatment choices. PeT effects
      are more individualized than conditional treatment effects from a randomized
      setting with the same observed characteristics. PeT effects can be easily
      aggregated to construct any of the mean treatment effect parameters and, more
      importantly, are well suited to comprehend individual-level treatment effect
      heterogeneity. The paper presents the theory behind PeT effects, and applies it
      to study the variation in individual-level comparative effects of prostate cancer
      treatments on overall survival and costs.

PMID- 25620845
TI  - Multiple-Input Subject-Specific Modeling of Plasma Glucose Concentration for
      Feedforward Control.
AB  - The ability to accurately develop subject-specific, input causation models, for
      blood glucose concentration (BGC) for large input sets can have a significant
      impact on tightening control for insulin dependent diabetes. More specifically,
      for Type 1 diabetics (T1Ds), it can lead to an effective artificial pancreas
      (i.e., an automatic control system that delivers exogenous insulin) under extreme
      changes in critical disturbances. These disturbances include food consumption,
      activity variations, and physiological stress changes. Thus, this paper presents
      a free-living, outpatient, multiple-input, modeling method for BGC with strong
      causation attributes that is stable and guards against overfitting to provide an
      effective modeling approach for feedforward control (FFC). This approach is a
      Wiener block-oriented methodology, which has unique attributes for meeting
      critical requirements for effective, long-term, FFC.

PMID- 25620846
TI  - New "Tau-Leap" Strategy for Accelerated Stochastic Simulation.
AB  - The "Tau-Leap" strategy for stochastic simulations of chemical reaction systems
      due to Gillespie and co-workers has had considerable impact on various
      applications. This strategy is reexamined with Chebyshev's inequality for random
      variables as it provides a rigorous probabilistic basis for a measured tau-leap
      thus adding significantly to simulation efficiency. It is also shown that
      existing strategies for simulation times have no probabilistic assurance that
      they satisfy the tau-leap criterion while the use of Chebyshev's inequality leads
      to a specified degree of certainty with which the tau-leap criterion is
      satisfied. This reduces the loss of sample paths which do not comply with the tau
      leap criterion. The performance of the present algorithm is assessed, with
      respect to one discussed by Cao et al. (J. Chem. Phys.2006, 124, 044109), a
      second pertaining to binomial leap (Tian and Burrage J. Chem. Phys.2004, 121,
      10356; Chatterjee et al. J. Chem. Phys.2005, 122, 024112; Peng et al. J. Chem.
      Phys.2007, 126, 224109), and a third regarding the midpoint Poisson leap (Peng et
      al., 2007; Gillespie J. Chem. Phys.2001, 115, 1716). The performance assessment
      is made by estimating the error in the histogram measured against that obtained
      with the so-called stochastic simulation algorithm. It is shown that the current
      algorithm displays notably less histogram error than its predecessor for a fixed
      computation time and, conversely, less computation time for a fixed accuracy.
      This computational advantage is an asset in repetitive calculations essential for
      modeling stochastic systems. The importance of stochastic simulations is derived
      from diverse areas of application in physical and biological sciences, process
      systems, and economics, etc. Computational improvements such as those reported
      herein are therefore of considerable significance.

PMID- 25620847
TI  - Do Student Evaluations of University Reflect Inaccurate Beliefs or Actual
      Experience? A Relative Rank Model.
AB  - It was shown that student satisfaction ratings are influenced by context in ways
      that have important theoretical and practical implications. Using questions from
      the UK's National Student Survey, the study examined whether and how students'
      expressed satisfaction with issues such as feedback promptness and instructor
      enthusiasm depends on the context of comparison (such as possibly inaccurate
      beliefs about the feedback promptness or enthusiasm experienced at other
      universities) that is evoked. Experiment 1 found strong effects of experimentally
      provided comparison context-for example, satisfaction with a given feedback time
      depended on the time's relative position within a context. Experiment 2 used a
      novel distribution-elicitation methodology to determine the prior beliefs of
      individual students about what happens in universities other than their own. It
      found that these beliefs vary widely and that students' satisfaction was
      predicted by how they believed their experience ranked within the distribution of
      others' experiences. A third study found that relative judgement principles also
      predicted students' intention to complain. An extended model was developed to
      show that purely rank-based principles of judgement can account for findings
      previously attributed to range effects. It was concluded that satisfaction
      ratings and quality of provision are different quantities, particularly when the
      implicit context of comparison includes beliefs about provision at other
      universities. Quality and satisfaction should be assessed separately, with
      objective measures (such as actual times to feedback), rather than subjective
      ratings (such as satisfaction with feedback promptness), being used to measure
      quality wherever practicable. (c) 2014 The Authors. Journal of Behavioral
      Decision Making published by John Wiley & Sons Ltd.

PMID- 25620849
TI  - Combining the Masking and Scaffolding Modalities of Colloidal Crystal Templates:
      Plasmonic Nanoparticle Arrays with Multiple Periodicities.
AB  - Surface patterns with prescribed structures and properties are highly desirable
      for a variety of applications. Increasing the heterogeneity of surface patterns
      is frequently required. This work opens a new avenue toward creating nanoparticle
      arrays with multiple periodicities by combining two generally separately applied
      modalities (i.e., scaffolding and masking) of a monolayer colloidal crystal (MCC)
      template. Highly ordered, loosely packed binary and ternary surface patterns are
      realized by a single-step thermal treatment of a gold thin-film-coated MCC and a
      nonclose-packed MCC template. Our approach enables control of the parameters
      defining these nanoscale binary and ternary surface patterns, such as particle
      size, shape, and composition, as well as the interparticle spacing. This
      technique enables preparation of well-defined binary and ternary surface patterns
      to achieve customized plasmonic properties. Moreover, with their easy
      programmability and excellent scalability, the binary and ternary surface
      patterns presented here could have valuable applications in nanophotonics and
      biomedicine. Specific examples include biosensing via surface-enhanced Raman
      scattering, fabrication of plasmonic-enhanced solar cells, and water splitting.

PMID- 25620848
TI  - Mesoporous Silica Nanoparticles Coated by Layer-by-Layer Self-assembly Using
      Cucurbit[7]uril for in Vitro and in Vivo Anticancer Drug Release.
AB  - Mesoporous silica nanoparticles (MSNs) are promising solid supports for
      controlled anticancer drug delivery. Herein, we report biocompatible layer-by
      layer (LbL) coated MSNs (LbL-MSNs) that are designed and crafted to release
      encapsulated anticancer drugs, e.g., doxorubicin hydrochloride (DOX), by changing
      the pH or by adding competitive agents. The LbL coating process comprises bis
      aminated poly(glycerol methacrylate)s (BA-PGOHMAs) and cucurbit[7]uril (CB[7]),
      where CB[7] serves as a molecular bridge holding two different bis-aminated
      polymeric layers together by means of host-guest interactions. This integrated
      nanosystem is tuned to respond under specific acidic conditions or by adding
      adamantaneamine hydrochloride (AH), attributed to the competitive binding of
      hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSN hybrids possess
      excellent biostability, negligible premature drug leakage at pH 7.4, and
      exceptional stimuli-responsive drug release performance. The pore sizes of the
      MSNs and bis-aminated compounds (different carbon numbers) of BA-PGOHMAs have
      been optimized to provide effective integrated nanosystems for the loading and
      release of DOX. Significantly, the operating pH for the controlled release of DOX
      matches the acidifying endosomal compartments of HeLa cancer cells, suggesting
      that these hybrid nanosystems are good candidates for autonomous anticancer drug
      nanocarriers actuated by intracellular pH changes without any invasive external
      stimuli. The successful cellular uptake and release of cargo, e.g., propidium
      iodide (PI), in human breast cancer cell line MDA-231 from PI-loaded LbL-MSNs
      have been confirmed by confocal laser scanning microscopy (CLSM), while the
      cytotoxicities of DOX-loaded LbL-MSNs have been quantified by the Cell Counting
      Kit-8 (CCK-8) viability assay against HeLa cell lines and fibroblast L929 cell
      lines. The uptake of DOX-loaded LbL-MSNs by macrophages can be efficiently
      reduced by adding biocompatible hydrophilic poly(ethylene glycol) or CB[7]
      without destroying the capping. In vivo tumor-growth inhibition experiments with
      BALB/c nude mice demonstrated a highly efficient tumor-growth inhibition rate of
      DOX-loaded LbL-MSNs, suggesting that the novel type of LbL-MSN materials hold
      great potentials in anticancer drug delivery.

PMID- 25620850
TI  - Newborn screening and diagnosis of mucopolysaccharidoses: application of tandem
      mass spectrometry.
AB  - Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by
      the deficiency of lysosomal enzymes. The enzymes are required to break down
      glycosaminoglycans (GAGs) that help build bone, cartilage, tendons, corneas, skin
      and connective tissue. In patients with MPS, a missing enzyme leads to the
      accumulation of GAGs in the cells, blood, connective tissues, and multiple
      organs. The consequence is permanent, with progressive cellular damage affecting
      patients' appearance, physical abilities, organ and system function, and skeletal
      and mental development. The measurement of each specific GAG in a variety of
      specimens is required to establish the correlation between GAGs and physiological
      status of patients and/or prognosis and pathogenesis of the disease and to
      separate the patients with MPS from the healthy controls. We have developed a
      highly accurate, sensitive, and cost-effective liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method for measurements of disaccharides derived from
      four specific GAGs [chondroitin sulfate (CS), dermatan sulfate (DS), heparan
      sulfate (HS), and keratan sulfate (KS)]. Disaccharides were produced by specific
      enzyme digestion of each GAG, and subsequently, quantified by negative ion mode
      of multiple reaction monitoring. Subclasses of GAGs with the same molecular
      weights can be separated by liquid chromatography. We have also developed another
      GAG assay by high-throughput mass spectrometry (HT-MS/MS). The HT-MS/MS consists
      of an integrated solid phase extraction robot that binds and de-salts samples
      from assay plates and directly injects them into a MS/MS detector, reducing
      sample processing time to within ten seconds. HT-MS/MS consequently yields much
      faster throughput than conventional LC-MS/MS-based methods; however, the HT-MS/MS
      system does not use a chromatographic step, and therefore, cannot separate GAGs
      that have the same molecular weights. Both techniques can be applied to the
      analysis of dried blood spots, blood, and urine specimens. In this review, we
      describe the assay methods for GAGs and the application to newborn screening and
      diagnosis of MPS.

PMID- 25620851
TI  - In silico optimization for production of biomass and biofuel feedstocks from
      microalgae.
AB  - Optimization of the production rate of biomass rich in N (e.g. for protein) or C
      (e.g. for biofuels) is key to making algae-based technology commercially viable.
      Creating the appropriate conditions to achieve this is a challenge; operational
      permutations are extensive, while geographical variations localise effective
      methods of cultivation when utilising natural illumination. As an aid to
      identifying suitable operational envelopes, a mechanistic acclimative model of
      microalgae growth is used for the first time to simulate production in virtual
      systems over a broad latitudinal range. Optimization of production is achieved
      through selection of strain characteristics, system optical depth, nutrient
      supply, and dilution regimes for different geographic and seasonal illumination
      profiles. Results reveal contrasting requirements for optimising biomass vs
      biofuels production. Trade-offs between maximising areal and volumetric
      production while conserving resources, plus hydrodynamic limits on reactor
      design, lead to quantifiable constraints for optimal operational permutations.
      Simulations show how selection of strains with a high maximum growth rate, Um ,
      remains the prime factor enabling high productivity. Use of an f/2 growth medium
      with a culture dilution rate set at ~25 % of Um delivers sufficient nutrition for
      optimal biomass production. Further, sensitivity to the balance between areal and
      volumetric productivity leads to a well-defined critical depth at ~0.1 m at which
      areal biofuel production peaks with use of a low concentration f/4 growth medium
      combined with a dilution rate ~15 % of Um . Such analyses, and developments
      thereof, will aid in developing a decision support tool to enable more productive
      methods of cultivation.

PMID- 25620852
TI  - The role of photo-osmotic adaptation in semi-continuous culture and lipid
      particle release from Dunaliella viridis.
AB  - Although great efforts have been made to elucidate the phenotypic responses of
      alga to varying levels of nutrients, osmotic environments, and photosynthetically
      active radiation intensities, the role of interactions among these variables is
      largely nebulous. Here, we describe a general method for establishing and
      maintaining semi-continuous cultures of the halophilic microalgal production
      strain, Dunaliella viridis, that is independent of variations in salinity and
      illumination intensity. Using this method, the cultures were evaluated to
      elucidate the overlapping roles of photosynthetic and osmotic adaptation on the
      accumulation and compositional variation of the biomass, photosynthetic
      productivity, and physiological biomarkers, as well as spectroscopic and
      morphological details at the single-cell level. Correlation matrices defining the
      relationships among the observables and based on variation of the illumination
      intensity and salinity were constructed for predicting bioproduct yields for
      varying culture conditions. Following maintenance of stable cultures for 6-week
      intervals, phenotypic responses to photo-osmotic drift were explored using a
      combination of single-cell hyperspectral fluorescence imaging and flow cytometry.
      In addition to morphological changes, release of lipid microparticles from the
      cells that is disproportionate to cell lysis was observed under hypotonic drift,
      indicating the existence of a reversible membrane permeation mechanism in
      Dunaliella. This phenomenon introduces the potential for low-cost strategies for
      recovering lipids and pigments from the microalgae by minimizing the requirement
      for energy intensive harvesting and dewatering of the biomass. The results should
      be applicable to outdoor culture, where seasonal changes resulting in variable
      solar flux and precipitation and evaporation rates are anticipated.

PMID- 25620853
TI  - Within-guild dietary discrimination from 3-D textural analysis of tooth microwear
      in insectivorous mammals.
AB  - Resource exploitation and competition for food are important selective pressures
      in animal evolution. A number of recent investigations have focused on linkages
      between diversification, trophic morphology and diet in bats, partly because
      their roosting habits mean that for many bat species diet can be quantified
      relatively easily through faecal analysis. Dietary analysis in mammals is
      otherwise invasive, complicated, time consuming and expensive. Here we present
      evidence from insectivorous bats that analysis of three-dimensional (3-D)
      textures of tooth microwear using International Organization for Standardization
      (ISO) roughness parameters derived from sub-micron surface data provides an
      additional, powerful tool for investigation of trophic resource exploitation in
      mammals. Our approach, like scale-sensitive fractal analysis, offers considerable
      advantages over two-dimensional (2-D) methods of microwear analysis, including
      improvements in robustness, repeatability and comparability of studies. Our
      results constitute the first analysis of microwear textures in carnivorous
      mammals based on ISO roughness parameters. They demonstrate that the method is
      capable of dietary discrimination, even between cryptic species with subtly
      different diets within trophic guilds, and even when sample sizes are small. We
      find significant differences in microwear textures between insectivore species
      whose diet contains different proportions of 'hard' prey (such as beetles) and
      'soft' prey (such as moths), and multivariate analyses are able to distinguish
      between species with different diets based solely on their tooth microwear
      textures. Our results show that, compared with previous 2-D analyses of microwear
      in bats, ISO roughness parameters provide a much more sophisticated
      characterization of the nature of microwear surfaces and can yield more robust
      and subtle dietary discrimination. ISO-based textural analysis of tooth microwear
      thus has a useful role to play, complementing existing approaches, in trophic
      analysis of mammals, both extant and extinct.

PMID- 25620854
TI  - Heme oxygenase-1-mediated host cell response inhibits the susceptibility of
      prostate cancer cells to retroviral infection and retards their proliferation.
AB  - Xenotropic murine leukemia virus-related virus (XMRV) resembles endogenous murine
      leukemia virus and was used in this study as a model for a new retrovirus
      infecting human cells. We demonstrate that induction of an HO-1-mediated host
      cell response inhibited the susceptibility of LNCaP prostate cancer cells to XMRV
      infection and efficiently retarded the growth of these prostate cancer cells. Our
      studies delineate a role of HO-1 in the host defense against retroviral
      infections and may provide novel therapeutic strategies for the treatment of HO-1
      sensitive prostate cancer.

PMID- 25620855
TI  - Supplementary Role of Health Metrics for Reducing Total Fertility Rate in a North
      Indian State.
AB  - Reducing Total Fertility Rate (TFR) amongst rural Indian couples from the current
      level is a significant challenge to the population control policies relying
      solely on the Government efforts. REACH strategy, based on health metrics,
      succeeded in lowering the TFR below replacement levels in a rural population of
      more than 300,000 in Rajasthan. The REACH strategy was first developed and
      demonstrated success in decreasing TFR in a pilot project by SHARE India in
      Medchal region of Andhra Pradesh utilizing designated workers, and was replicated
      in Rajgarh District of Rajasthan in cooperation with Bhoruka Charitable Trust
      (supervisor of ICDS and NRHM health workers in Rajgarh) using Government health
      workers. The success of the REACH strategy in both Rajasthan and previously in
      Andhra Pradesh holds promise as a tool to reduce TFR in other areas of rural
      India.

PMID- 25620856
TI  - Mono-isotope Prediction for Mass Spectra Using Bayes Network.
AB  - Mass spectrometry is one of the widely utilized important methods to study
      protein functions and components. The challenge of mono-isotope pattern
      recognition from large scale protein mass spectral data needs computational
      algorithms and tools to speed up the analysis and improve the analytic results.
      We utilized naive Bayes network as the classifier with the assumption that the
      selected features are independent to predict mono-isotope pattern from mass
      spectrometry. Mono-isotopes detected from validated theoretical spectra were used
      as prior information in the Bayes method. Three main features extracted from the
      dataset were employed as independent variables in our model. The application of
      the proposed algorithm to publicMo dataset demonstrates that our naive Bayes
      classifier is advantageous over existing methods in both accuracy and
      sensitivity.

PMID- 25620858
TI  - Tighten after Relax: Minimax-Optimal Sparse PCA in Polynomial Time.
AB  - We provide statistical and computational analysis of sparse Principal Component
      Analysis (PCA) in high dimensions. The sparse PCA problem is highly nonconvex in
      nature. Consequently, though its global solution attains the optimal statistical
      rate of convergence, such solution is computationally intractable to obtain.
      Meanwhile, although its convex relaxations are tractable to compute, they yield
      estimators with suboptimal statistical rates of convergence. On the other hand,
      existing nonconvex optimization procedures, such as greedy methods, lack
      statistical guarantees. In this paper, we propose a two-stage sparse PCA
      procedure that attains the optimal principal subspace estimator in polynomial
      time. The main stage employs a novel algorithm named sparse orthogonal iteration
      pursuit, which iteratively solves the underlying nonconvex problem. However, our
      analysis shows that this algorithm only has desired computational and statistical
      guarantees within a restricted region, namely the basin of attraction. To obtain
      the desired initial estimator that falls into this region, we solve a convex
      formulation of sparse PCA with early stopping. Under an integrated analytic
      framework, we simultaneously characterize the computational and statistical
      performance of this two-stage procedure. Computationally, our procedure converges
      at the rate of [Formula: see text] within the initialization stage, and at a
      geometric rate within the main stage. Statistically, the final principal subspace
      estimator achieves the minimax-optimal statistical rate of convergence with
      respect to the sparsity level s*, dimension d and sample size n. Our procedure
      motivates a general paradigm of tackling nonconvex statistical learning problems
      with provable statistical guarantees.

PMID- 25620859
TI  - Mode Estimation for High Dimensional Discrete Tree Graphical Models.
AB  - This paper studies the following problem: given samples from a high dimensional
      discrete distribution, we want to estimate the leading (delta, rho)-modes of the
      underlying distributions. A point is defined to be a (delta, rho)-mode if it is a
      local optimum of the density within a delta-neighborhood under metric rho. As we
      increase the "scale" parameter delta, the neighborhood size increases and the
      total number of modes monotonically decreases. The sequence of the (delta, rho)
      modes reveal intrinsic topographical information of the underlying distributions.
      Though the mode finding problem is generally intractable in high dimensions, this
      paper unveils that, if the distribution can be approximated well by a tree
      graphical model, mode characterization is significantly easier. An efficient
      algorithm with provable theoretical guarantees is proposed and is applied to
      applications like data analysis and multiple predictions.

PMID- 25620857
TI  - In vivo photoacoustic imaging of breast cancer tumor with HER2-targeted
      nanodiamonds.
AB  - Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for
      photoacoustic (PA) imaging in biological tissues due to their good
      biocompatibility and high optical absorbance in the near-infrared (NIR) range.
      Acid treated NDs are oxidized to form carboxyl groups on the surface,
      functionalized with polyethylene glycol (PEG) and human epidermal growth factor
      receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of
      the specific binding of the ligand conjugated NDs to the HER2-overexpressing
      murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly
      delineated from the surrounding normal tissue at wavelength of 820 nm under the
      PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher
      accumulation in HER2 positive breast tumors as compared to non-targeted NDs after
      intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in
      HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This
      demonstrates that targeting moiety conjugated NDs have great potential for the
      sensitive detection of cancer tumors and provide an attractive delivery strategy
      for anti-cancer drugs.

PMID- 25620860
TI  - Accelerated Mini-batch Randomized Block Coordinate Descent Method.
AB  - We consider regularized empirical risk minimization problems. In particular, we
      minimize the sum of a smooth empirical risk function and a nonsmooth
      regularization function. When the regularization function is block separable, we
      can solve the minimization problems in a randomized block coordinate descent
      (RBCD) manner. Existing RBCD methods usually decrease the objective value by
      exploiting the partial gradient of a randomly selected block of coordinates in
      each iteration. Thus they need all data to be accessible so that the partial
      gradient of the block gradient can be exactly obtained. However, such a "batch"
      setting may be computationally expensive in practice. In this paper, we propose a
      mini-batch randomized block coordinate descent (MRBCD) method, which estimates
      the partial gradient of the selected block based on a mini-batch of randomly
      sampled data in each iteration. We further accelerate the MRBCD method by
      exploiting the semi-stochastic optimization scheme, which effectively reduces the
      variance of the partial gradient estimators. Theoretically, we show that for
      strongly convex functions, the MRBCD method attains lower overall iteration
      complexity than existing RBCD methods. As an application, we further trim the
      MRBCD method to solve the regularized sparse learning problems. Our numerical
      experiments shows that the MRBCD method naturally exploits the sparsity structure
      and achieves better computational performance than existing methods.

PMID- 25620861
TI  - Multivariate Regression with Calibration.
AB  - We propose a new method named calibrated multivariate regression (CMR) for
      fitting high dimensional multivariate regression models. Compared to existing
      methods, CMR calibrates the regularization for each regression task with respect
      to its noise level so that it is simultaneously tuning insensitive and achieves
      an improved finite-sample performance. Computationally, we develop an efficient
      smoothed proximal gradient algorithm which has a worst-case iteration complexity
      O(1/epsilon), where epsilon is a pre-specified numerical accuracy. Theoretically,
      we prove that CMR achieves the optimal rate of convergence in parameter
      estimation. We illustrate the usefulness of CMR by thorough numerical simulations
      and show that CMR consistently outperforms other high dimensional multivariate
      regression methods. We also apply CMR on a brain activity prediction problem and
      find that CMR is as competitive as the handcrafted model created by human
      experts.

PMID- 25620862
TI  - A STRICTLY CONTRACTIVE PEACEMAN-RACHFORD SPLITTING METHOD FOR CONVEX PROGRAMMING.
AB  - In this paper, we focus on the application of the Peaceman-Rachford splitting
      method (PRSM) to a convex minimization model with linear constraints and a
      separable objective function. Compared to the Douglas-Rachford splitting method
      (DRSM), another splitting method from which the alternating direction method of
      multipliers originates, PRSM requires more restrictive assumptions to ensure its
      convergence, while it is always faster whenever it is convergent. We first
      illustrate that the reason for this difference is that the iterative sequence
      generated by DRSM is strictly contractive, while that generated by PRSM is only
      contractive with respect to the solution set of the model. With only the
      convexity assumption on the objective function of the model under consideration,
      the convergence of PRSM is not guaranteed. But for this case, we show that the
      first t iterations of PRSM still enable us to find an approximate solution with
      an accuracy of O(1/t). A worst-case O(1/t) convergence rate of PRSM in the
      ergodic sense is thus established under mild assumptions. After that, we suggest
      attaching an underdetermined relaxation factor with PRSM to guarantee the strict
      contraction of its iterative sequence and thus propose a strictly contractive
      PRSM. A worst-case O(1/t) convergence rate of this strictly contractive PRSM in a
      nonergodic sense is established. We show the numerical efficiency of the strictly
      contractive PRSM by some applications in statistical learning and image
      processing.

PMID- 25620863
TI  - Effect of UV irradiation on Echinaceae purpureae interactions with free radicals
      examined by an X-band (9.3 GHz) EPR spectroscopy.
AB  - The effect of UVA (315-400 nm) irradiation on Echinaceae purpureae interactions
      with free radicals was examined by the use of electron paramagnetic resonance
      (EPR) spectroscopy. The changes of antioxidant properties of E. purpureae with
      time of UV irradiation from 10 to 110 min (10 min steps) were determined. DPPH as
      the paramagnetic reference was used in this study. Changes of EPR signals of the
      reference after interactions with nonirradiated and UV-irradiated E. purpureae
      were detected. Interactions of the tested E. purpureae samples caused decrease of
      the EPR signal of DPPH as the result of its antioxidant properties. The decrease
      of the amplitude of EPR line of DPPH was lower for interactions with UV
      irradiated E. purpureae. EPR examination confirmed antioxidant properties of E.
      purpureae. The weaker antioxidant properties of E. purpureae after UV irradiation
      were pointed out. E. purpureae should be storage in the dark. The tests bring to
      light usefulness of electron paramagnetic resonance with microwave frequency of
      9.3 GHz (an X-band) in examination of storage conditions of pharmacological
      herbs.

PMID- 25620864
TI  - Synthesis and molecular docking of novel non-competitive antagonists of GluK2
      receptor.
AB  - Here we present the synthesis, pharmacological activity, and molecular docking of
      novel non-competitive antagonists of GluK2 receptor. The compounds concerned are
      derivatives of indole and carbazole and are the second reported series of non
      competitive antagonists of the GluK2 receptor (the first one was also published
      by our group). The activity of the indole derivatives is in the micromolar range,
      as in the case of the first series of non-competitive GluK2 receptor antagonists.
      We have found that designed carbazole derivatives are devoid of activity. Active
      indole derivatives interact with the transduction domain of the GluK2 receptor,
      i.e., the domain which links the transmembrane region of the receptor with the
      agonist-binding domain. The binding pocket is situated within one receptor
      subunit.

PMID- 25620865
TI  - Imaging and patient-specific simulations for the Fontan surgery: current
      methodologies and clinical applications.

PMID- 25620866
TI  - Sparse Covariance Matrix Estimation With Eigenvalue Constraints.
AB  - We propose a new approach for estimating high-dimensional, positive-definite
      covariance matrices. Our method extends the generalized thresholding operator by
      adding an explicit eigenvalue constraint. The estimated covariance matrix
      simultaneously achieves sparsity and positive definiteness. The estimator is rate
      optimal in the minimax sense and we develop an efficient iterative soft
      thresholding and projection algorithm based on the alternating direction method
      of multipliers. Empirically, we conduct thorough numerical experiments on
      simulated datasets as well as real data examples to illustrate the usefulness of
      our method. Supplementary materials for the article are available online.

PMID- 25620867
TI  - A Common Elements Treatment Approach for Adult Mental Health Problems in Low- and
      Middle-Income Countries.
AB  - This paper describes the Common Elements Treatment Approach (CETA) for adults
      presenting with mood or anxiety problems developed specifically for use with lay
      counselors in low- and middle-income countries (LMIC). Details of the
      intervention development, training, supervision, and decision-making process are
      presented. Case vignettes are used as examples throughout. Preliminary findings
      are presented on counselor/supervisor performance and client outcomes from
      practice cases completed prior to randomized controlled trials (RCT) conducted at
      two sites for adult survivors of torture and/or systematic violence in (a)
      southern Iraq and (b) Thailand-Burma border. Data suggest that local supervisors
      and lay counselors with little prior mental health training or experience
      maintained fidelity to the model. The majority of pilot clients were retained in
      treatment, suggesting acceptability. Using the Reliable Change Index (RCI) for
      each individual we examined the number of clients above a minimal threshold (z >
      1.96) for each outcome. In Iraq 100% of clients had RCIs above the threshold for
      depression and posttraumatic stress, and 81.8% for impaired function. In
      Thailand, 81.3% of clients had RCIs above minimum threshold for depression, 68.8%
      for posttraumatic stress, and 37.5% for impaired function. Implementation of CETA
      is discussed in relation to cultural issues within LMIC. These findings, combined
      with US-based evidence, suggest that a common elements approach warrants further
      development and testing as a means for addressing the treatment gap for mental
      health problems in LMIC.

PMID- 25620868
TI  - Acting Locally and Globally: Dissemination and Implementation Around the World
      and Next Door.
AB  - Murray et al. (this issue) present a fascinating account of their international
      dissemination and implementation (D&I) research focused on training therapists in
      Thailand and Iraq to provide a modular treatment approach called Common Elements
      Treatment Approach to youth. In this commentary, we use Murray et al. as a
      springboard to discuss a few general conclusions about the current direction of
      D&I research. Specifically, we reflect on current D&I models, highlighting their
      ecological focus and their emphasis on stakeholder involvement. Next, we discuss
      the central importance of implementation supports such as treatment programs,
      training approaches, assessment and outcome monitoring tools, and organizational
      interventions. We conclude with a consideration of how D&I work that aims to
      adapt implementation supports for local needs represent a key path to our goal of
      sustainability.

PMID- 25620869
TI  - Continuous Flow Aerobic Alcohol Oxidation Reactions Using a Heterogeneous Ru(OH)
      x /Al2O3 Catalyst.
AB  - Ru(OH) x /Al2O3 is among the more versatile catalysts for aerobic alcohol
      oxidation and dehydrogenation of nitrogen heterocycles. Here, we describe the
      translation of batch reactions to a continuous-flow method that enables high
      steady-state conversion and single-pass yields in the oxidation of benzylic
      alcohols and dehydrogenation of indoline. A dilute source of O2 (8% in N2) was
      used to ensure that the reaction mixture, which employs toluene as the solvent,
      is nonflammable throughout the process. A packed bed reactor was operated
      isothermally in an up-flow orientation, allowing good liquid-solid contact.
      Deactivation of the catalyst during the reaction was modeled empirically, and
      this model was used to achieve high conversion and yield during extended
      operation in the aerobic oxidation of 2-thiophene methanol (99+% continuous yield
      over 72 h).

PMID- 25620870
TI  - The Psychometric Latent Agreement Model (PLAM) for Discrete Latent Variables
      Measured by Multiple Items.
AB  - The Psychometric Latent Agreement Model (PLAM) is proposed for estimating the
      subpopulation membership of individuals (e.g., satisfactory performers vs.
      unsatisfactory performers) at discrete levels of multiple latent trait variables.
      A binary latent Type variable is introduced to take account of the possibility
      that, for a given set of observed variables, the latent group memberships of some
      individuals are indeterminate. The latent Type variable allows for separating
      individuals who can reliably be assigned to satisfactory versus unsatisfactory
      performers classes from those individuals whose ratings do not contain the
      necessary information to make the class assignment possible for a particular set
      of rating items. Agreements among discrete latent trait variables are also
      estimated. The PLAM was illustrated with two examples using real data on
      behavioral rating measures. One example involved ratings of two behavioral
      constructs by a single rater type, whereas the other involved ratings of one
      construct by three rater types. Implications were presented for using behavioral
      ratings to determine the subpopulation membership, such as qualified versus
      unqualified groupings in hiring decisions and pass versus fail groupings in
      performance evaluations.

PMID- 25620871
TI  - EPSTEIN -BARR VIRUS ASSOCIATION WITH MALIGNANT LYMPHOMA SUBGROUPS IN ZARIA,
      NIGERIA.
AB  - Epstein-Barr virus (EBV) is said to infect more than 90% of humans worldwide with
      latent infection for life. A recognized carcinogen, EBV is linked to malignant
      lymphoma (ML) subtypes of Burkitt's lymphoma (BL), plasmablastic lymphoma,
      diffuse large cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL). We report the
      association of EBV with ML in a segment of our patient population. Paraffin
      blocks from the archives of ABUTH, Zaria were used to construct tissue microarray
      sections stained using 30 monoclonal antibodies for common Non-Hodgkin's
      lymphoma/ Hodgkin's lymphoma antigen and chromogenic in situ hybridization (CISH)
      for EBV-encoded RNA were done. Fewer associations of ML with EBV were found than
      reported from elsewhere in Africa.

PMID- 25620872
TI  - Cortical inputs to the middle temporal visual area in New World owl monkeys.
AB  - We made eight retrograde tracer injections into the middle temporal visual area
      (MT) of three New World owl monkeys (Aotus nancymaae). These injections were
      placed across the representation of the retina in MT to allow us to compare the
      locations of labeled cells in other areas in order to provide evidence for any
      retinotopic organization in those areas. Four regions projected to MT: 1) early
      visual areas, including V1, V2, V3, the dorsolateral visual area, and the
      dorsomedial visual area, provided topographically organized inputs to MT; 2) all
      areas in the MT complex (the middle temporal crescent, the middle superior
      temporal area, and the fundal areas of the superior temporal sulcus) projected to
      MT. Somewhat variably across injections, neurons were labeled in other parts of
      the temporal lobe; 3) regions in the location of the medial visual area, the
      posterior parietal cortex, and the lateral sulcus provided other inputs to MT; 4)
      finally, projections from the frontal eye field, frontal visual field, and
      prefrontal cortex were also labeled by our injections. These results further
      establish the sources of input to MT, and provide direct evidence within and
      across cases for retinotopic patterns of projections from early visual areas to
      MT.

PMID- 25620873
TI  - Noninvasive evaluation of left ventricular force-frequency relationships by
      measuring carotid arterial wave intensity during exercise stress.
AB  - BACKGROUND AND PURPOSE: Estimation of the contractility of the left ventricle
      during exercise is important in drawing up a protocol of cardiac rehabilitation.
      It has been demonstrated that color Doppler- and echo tracking-derived carotid
      arterial wave intensity is a sensitive index of global left ventricular (LV)
      contractility. We assessed the feasibility of measuring carotid arterial wave
      intensity and determining force-frequency (contractility-heart rate) relations
      (FFRs) during exercise totally noninvasively. METHODS: We measured carotid
      arterial wave intensity with a combined color Doppler and echo tracking system in
      25 healthy young male volunteers (age 20.8 +/- 1.2 years) at rest and during
      exercise. FFRs were constructed by plotting the maximum value of wave intensity
      (WD1) against heart rate (HR). RESULTS: We first confirmed that HR increased
      linearly with an increase in work load in each subject (r (2) = 0.95 +/- 0.04).
      WD1 increased linearly with an increase in HR. The goodness-of-fit of the
      regression line of WD1 on HR in each subject was very high (r (2) = 0.48-0.94, p
      < 0.0001, respectively). The slope of the WD1-HR relation ranged 0.30-2.20
      [m/s(3) (beat/min)]. CONCLUSIONS: Global LV FFRs can be generated in healthy
      young volunteers with an entirely noninvasive combination of exercise and wave
      intensity. These data should show the potential usefulness of the FFR in the
      context of cardiac rehabilitation.

PMID- 25620874
TI  - Non-sulfate sulfur in fine aerosols across the United States: Insight for
      organosulfate prevalence.
AB  - We investigated the discrepancies in long-term sulfur measurements from 2000 to
      2012 by two separate speciation methods, X-ray fluorescence (XRF) spectroscopy
      and ion chromatography (IC) across the United States (334 sites). Overall, there
      was a good correlation between sulfur measurements by XRF spectroscopy and IC (R
      >= 0.90 for most of the sites). However, the inorganic sulfate measured by ion
      chromatography was not sufficient to account for all the sulfur measured by XRF
      spectroscopy at many of the sites. Discrepancies were observed with the high
      ratios of sulfur measured by XRF spectroscopy to that by IC. Such high ratios
      also exhibited seasonal variation, and differed across land use types;
      significant differences occurred at locations classified as forest, agriculture,
      and mobile, but not in locations classified as commercial, desert, industrial,
      and residential. On average, the excess, or non-sulfate, sulfur (unmeasured
      organic sulfur or other inorganic species of sulfur) was variable and observed as
      high as ~13% of organic carbon and ~2% of PM2.5. The contribution of such assumed
      organosulfur was larger in the eastern region than other geographical locations
      in the United States. Besides the temporal and spatial trends, the additional
      sulfur was found to be related to other factors such as aerosol acidity and
      emission sources. The results suggest that these unmeasured sulfur species could
      have significant contribution to aerosol burden, and the understanding of these
      could help to control PM2.5 levels and to assess other effects of sulfur
      aerosols.

PMID- 25620875
TI  - Predicting Onset and Duration of Airborne Allergenic Pollen Season in the United
      States.
AB  - Allergenic pollen is one of the main triggers of Allergic Airway Disease (AAD)
      affecting 5% to 30% of the population in industrialized countries. A modeling
      framework has been developed using correlation and collinearity analyses,
      simulated annealing, and stepwise regression based on nationwide observations of
      airborne pollen counts and climatic factors to predict the onsets and durations
      of allergenic pollen seasons of representative trees, weeds and grass in the
      contiguous United States. Main factors considered are monthly, seasonal and
      annual mean temperatures and accumulative precipitations, latitude, elevation,
      Growing Degree Day (GDD), Frost Free Day (FFD), Start Date (SD) and Season Length
      (SL) in the previous year. The estimated mean SD and SL for birch (Betula), oak
      (Quercus), ragweed (Ambrosia), mugwort (Artemisia) and grass (Poaceae) pollen
      season in 1994-2010 are mostly within 0 to 6 days of the corresponding
      observations for the majority of the National Allergy Bureau (NAB) monitoring
      stations across the contiguous US. The simulated spatially resolved maps for
      onset and duration of allergenic pollen season in the contiguous US are
      consistent with the long term observations.

PMID- 25620876
TI  - Fine mapping of RBG2, a quantitative trait locus for resistance to Burkholderia
      glumae, on rice chromosome 1.
AB  - Bacterial grain rot (BGR), caused by the bacterial pathogen Burkholderia glumae,
      is a destructive disease of rice. At anthesis, rice panicles are attacked by the
      pathogen, and the infection causes unfilled or aborted grains, reducing grain
      yield and quality. Thus, increasing the level of BGR resistance is an important
      objective for rice breeding. A quantitative trait locus (QTL) on rice chromosome
      1 that controls BGR resistance was previously detected in backcross inbred lines
      (BILs) derived from a cross between Kele, a resistant traditional lowland
      cultivar (indica) that originated in India, and Hitomebore, a susceptible modern
      lowland cultivar (temperate japonica) from Japan. Further genetic analyses using
      a BC3F6 population derived from a cross between a resistant BIL (BC2F5) and
      Hitomebore confirmed that a QTL for BGR resistance was located on the long arm of
      chromosome 1. To define more precisely the chromosomal region underlying this
      QTL, we identified nine BC2F6 plants in which recombination occurred near the
      QTL. Substitution mapping using homozygous recombinant and nonrecombinant plants
      demonstrated that the QTL, here designated as Resistance to Burkholderia glumae 2
      (RBG2), was located in a 502-kb interval defined by simple sequence repeat
      markers RM1216 and RM11727.

PMID- 25620878
TI  - An InDel-based linkage map of hot pepper (Capsicum annuum).
AB  - Two independent pepper (Capsicum annuum) genomes were published recently, opening
      a new era of molecular genetics research on pepper. However, pepper molecular
      marker technologies are still mainly focusing on the simple sequence repeats
      derived from public database or genomic library. The development and application
      of the third generation marker system such as single nucleotide polymorphisms,
      structure variations as well as insertion/deletion polymorphisms (InDels) is
      still in its infancy. In the present study, we developed InDel markers for pepper
      genetic mapping with the convenience of two whole-genome re-sequenced inbred
      lines BA3 (C. annuum) and B702 (C. annuum). A total of 154,519 and 149,755 InDel
      (1-5 bp) sites were identified for BA3 and B702, respectively, by the alignment
      of re-sequencing reads to Zunla-1 reference genome. Then, 14,498 InDel sites
      (only 4 and 5 bp) that are different between BA3 and B702 were predicted.
      Finally, within a random set of 1,000 primer pairs, 251 InDel markers were
      validated and mapped onto a linkage map using F2 population derived from the
      intraspecific cross BA3 * B702. The first InDel-based map, named as BB-InDel map,
      consisted of 12 linkage groups, covered a genetic distance of 1,178.01 cM and the
      average distance between bin markers was 5.01 cM. Compared to the Zunla-1
      reference physical map, high consistency was observed on all 12 chromosomes, and
      the total length of scaffold anchored and physical distance covered by this map
      was 299.66 and 2,558.68 Mb, respectively, which accounted for 8.95 and 76.38 % of
      the Zunla-1 reference genome (3.35 Gb), respectively. Furthermore, 37 scaffolds
      (total length of 36.21 Mb) from the pseudo-chromosome (P0) of the current genome
      assembly were newly assigned to the corresponding chromosomes by 40 InDel
      markers. Thus, this map provided good genome coverage and would be useful for
      basic and applied research in pepper.

PMID- 25620877
TI  - Differential expression of the HvCslF6 gene late in grain development may explain
      quantitative differences in (1,3;1,4)-beta-glucan concentration in barley.
AB  - The cellulose synthase-like gene HvCslF6, which is essential for (1,3;1,4)-beta
      glucan biosynthesis in barley, collocates with quantitative trait loci (QTL) for
      grain (1,3;1,4)-beta-glucan concentration in several populations, including CDC
      Bold * TR251. Here, an alanine-to-threonine substitution (caused by the only non
      synonymous difference between the CDC Bold and TR251 HvCslF6 alleles) was mapped
      to a position within HvCSLF6 that seems unlikely to affect enzyme stability or
      function. Consistent with this, transient expression of full-length HvCslF6 cDNAs
      from CDC Bold and TR251 in Nicotianabenthamiana led to accumulation of similar
      amounts of (1,3;1,4)-beta-glucan accumulation. Monitoring of HvCslF6 transcripts
      throughout grain development revealed a significant difference late in grain
      development (more than 30 days after pollination), with TR251 [the parent with
      higher grain (1,3;1,4)-beta-glucan] exhibiting higher transcript levels than CDC
      Bold. A similar difference was observed between Beka and Logan, the parents of
      another population in which a QTL had been mapped in the HvCslF6 region.
      Sequencing of a putative promoter region of HvCslF6 revealed numerous
      polymorphisms between CDC Bold and TR251, but none between Beka and Logan. While
      the results of this work indicate that naturally occurring quantitative
      differences in (1,3;1,4)-beta-glucan accumulation may be due to cis-regulated
      differences in HvCslF6 expression, these could not be attributed to any specific
      DNA sequence polymorphism. Nevertheless, information on HvCslF6 sequence
      polymorphism was used to develop molecular markers that could be used in barley
      breeding to select for the desired [low or high (1,3;1,4)-beta-glucan] allele of
      the QTL.

PMID- 25620879
TI  - Single-nucleotide polymorphism identification and genotyping in Camelina sativa.
AB  - Camelina sativa, a largely relict crop, has recently returned to interest due to
      its potential as an industrial oilseed. Molecular markers are key tools that will
      allow C. sativa to benefit from modern breeding approaches. Two complementary
      methodologies, capture of 3' cDNA tags and genomic reduced-representation
      libraries, both of which exploited second generation sequencing platforms, were
      used to develop a low density (768) Illumina GoldenGate single nucleotide
      polymorphism (SNP) array. The array allowed 533 SNP loci to be genetically mapped
      in a recombinant inbred population of C. sativa. Alignment of the SNP loci to the
      C. sativa genome identified the underlying sequenced regions that would delimit
      potential candidate genes in any mapping project. In addition, the SNP array was
      used to assess genetic variation among a collection of 175 accessions of C.
      sativa, identifying two sub-populations, yet low overall gene diversity. The SNP
      loci will provide useful tools for future crop improvement of C. sativa.

PMID- 25620880
TI  - Genetic mapping and legume synteny of aphid resistance in African cowpea (Vigna
      unguiculata L. Walp.) grown in California.
AB  - The cowpea aphid Aphis craccivora Koch (CPA) is a destructive insect pest of
      cowpea, a staple legume crop in Sub-Saharan Africa and other semiarid warm
      tropics and subtropics. In California, CPA causes damage on all local cultivars
      from early vegetative to pod development growth stages. Sources of CPA resistance
      are available in African cowpea germplasm. However, their utilization in breeding
      is limited by the lack of information on inheritance, genomic location and marker
      linkage associations of the resistance determinants. In the research reported
      here, a recombinant inbred line (RIL) population derived from a cross between a
      susceptible California blackeye cultivar (CB27) and a resistant African breeding
      line (IT97K-556-6) was genotyped with 1,536 SNP markers. The RILs and parents
      were phenotyped for CPA resistance using field-based screenings during two main
      crop seasons in a 'hotspot' location for this pest within the primary growing
      region of the Central Valley of California. One minor and one major quantitative
      trait locus (QTL) were consistently mapped on linkage groups 1 and 7,
      respectively, both with favorable alleles contributed from IT97K-556-6. The major
      QTL appeared dominant based on a validation test in a related F2 population. SNP
      markers flanking each QTL were positioned in physical contigs carrying genes
      involved in plant defense based on synteny with related legumes. These markers
      could be used to introgress resistance alleles from IT97K-556-6 into susceptible
      local blackeye varieties by backcrossing.

PMID- 25620881
TI  - Investigation of the polyvinyl alcohol stabilization mechanism and adsorption
      properties on the surface of ternary mixed nanooxide AST 50 (Al2O3-SiO2-TiO2).
AB  - A new adsorbent consisting of fumed, mixed alumina, silica, and titania in
      various proportions (AST 50) was investigated. The studied material was prepared
      by chemical vapor deposition method. The diameter of AST 50 primary particles was
      equal to about 51 nm which denotes that it can be classified as a nanomaterial.
      In the presented paper, the adsorption properties of polyvinyl alcohol on the
      ternary oxide were investigated. The polymer macromolecules were characterized by
      two different molecular weights and degree of hydrolysis. The polymer adsorption
      reaches the maximum at pH 3 and decreases with the solution pH rise. The
      reduction of the adsorbed PVA macromolecules is related to the electrostatic
      repulsion forces occurring in the studied system. The AST 50 point of zero charge
      (pHpzc) obtained from the potentiometric titration is equal to 4.7. Due to the
      nonionic character of the analyzed macromolecular compound, the polymer
      attendance has an insignificant effect on the AST 50 surface charge density. In
      the case of the adsorbent particles zeta potential, the obtained dependencies are
      different in the absence and presence of PVA. The shift of the slipping plane and
      displacement of the counter-ions from Stern layer by the adsorbed polymer chains
      have the greatest effect on the zeta potential value. The stability measurements
      indicate that the AST 50 suspensions in the presence of the background
      electrolyte at pH 3 and 6 are unstable. In turn, in an alkaline medium the mixed
      oxide suspensions exhibit the highest durability, which is a result of a large
      number of the negative charges on the AST 50 surface. The addition of PVA 100
      significantly improves the suspension stability at pH 3 and 6; at higher pH
      value, the polymer presence does not influence the system durability. It is
      related to the steric and electrosteric stabilization of the colloidal particles
      by the adsorbed polyvinyl alcohol macromolecules.

PMID- 25620882
TI  - Rapid continuous microwave-assisted synthesis of silver nanoparticles to achieve
      very high productivity and full yield: from mechanistic study to optimal
      fabrication strategy.
AB  - Systematic studies of silver nanoparticle synthesis in a continuous-flow single
      mode microwave reactor using polyol process were performed, revealing that the
      synthesis is exceptionally effective to give very small metal particles at full
      reaction yield and very high productivity. Inlet concentration of silver nitrate
      or silver acetate, applied as metal precursors, varied between 10 and 50 mM, and
      flow rates ranged from 0.635 to 2.5 dm3/h, to give 3-24 s reaction time. Owing to
      its much higher reactivity, silver acetate was shown to be far superior substrate
      for the synthesis of small (10-20 nm) spherical silver nanoparticles within a few
      seconds. Its restricted solubility in ethylene glycol, applied as the solvent and
      reducing agent, appeared to be vital for effective separation of the stage of
      particle growth from its nucleation to enable rapid synthesis of small particles
      in a highly loaded system. This was not possible to obtain using silver nitrate.
      All the observations could perfectly be explained by a classical LaMer-Dinegar
      model of NPs' formation, but taking into account also nonisothermal character of
      the continuous-flow process and acetate dissolution in the reaction system. The
      performed studies indicate an optimal strategy for the high-yield fabrication of
      metal particles using polyol method.

PMID- 25620883
TI  - Comparison of FSH and hMG on ovarian stimulation outcome with a GnRH antagonist
      protocol in younger and advanced reproductive age women.
AB  - PURPOSE: To compare the embryo outcomes of in vitro fertilization/intra
      cytoplasmic sperm injection with a gonadotropin-releasing hormone (GnRH)
      antagonist protocol with follicle stimulating hormone (FSH) and with human
      menopausal gonadotropin (hMG). METHODS: We performed a retrospective cohort study
      in 465 patients. Stimulation was started by daily FSH injection, and either FSH
      was continued (FSH alone group) or hMG was administrated (FSH-hMG group) after
      administration of a GnRH antagonist. Primary outcomes were the embryo profile
      (number of retrieved, mature, and fertilized eggs, and morphologically good
      embryos on day 3) and endocrine profile. Secondary outcomes were the doses and
      durations of gonadotropin. Data were stratified by the patients' age into two
      groups: <35 years and >=35 years. RESULTS: In patients aged <35 years, the number
      of retrieved oocytes in the FSH alone group was significantly increased than that
      in the FSH-hMG group (13.7 vs 9.2, P = 0.04), while there was no difference at
      other age groups. The FSH-hMG group required a significantly greater amount of
      gonadotropins at any age (all ages, P < 0.001; <35 years, P = 0.013; >=35 years,
      P < 0.001). CONCLUSIONS: Exogenous FSH alone is probably sufficient for
      follicular development and hMG may not improve the embryo profile in a GnRH
      antagonist protocol across all age.

PMID- 25620884
TI  - Initial development and psychometric testing of an instrument to measure the
      quality of children's end-of-life care.
AB  - BACKGROUND: The field of pediatric palliative care is hindered by the lack of a
      well-defined, reliable, and valid method for measuring the quality of end-of-life
      care. METHODS: The study purpose was to develop and test an instrument to measure
      mothers' perspectives on the quality of care received before, at the time of, and
      following a child's death. In Phase 1, key components of quality end-of-life care
      for children were synthesized through a comprehensive review of research
      literature. These key components were validated in Phase 2 and then extended
      through focus groups with bereaved parents. In Phase 3, items were developed to
      assess structures, processes, and outcomes of quality end-of-life care then
      tested for content and face validity with health professionals. Cognitive testing
      was conducted through interviews with bereaved parents. In Phase 4, bereaved
      mothers were recruited through 10 children's hospitals/hospices in Canada to
      complete the instrument, and psychometric testing was conducted. RESULTS:
      Following review of 67 manuscripts and 3 focus groups with 10 parents, 141 items
      were initially developed. The overall content validity index for these items was
      0.84 as rated by 7 health professionals. Based on feedback from health
      professionals and cognitive testing with 6 parents, a 144-item instrument was
      finalized for further testing. In Phase 4, 128 mothers completed the instrument,
      31 of whom completed it twice. Test-retest reliability, internal consistency, and
      construct validity were demonstrated for six subscales: Connect With Families,
      Involve Parents, Share Information With Parents, Share Information Among Health
      Professionals, Support Parents, and Provide Care at Death. Additional items with
      content validity were grouped in four domains: Support the Child, Support
      Siblings, Provide Bereavement Follow-up, and Structures of Care. Forty-eight
      items were deleted through psychometric testing, leaving a 95-item instrument.
      CONCLUSIONS: There is good initial evidence for the reliability and validity of
      this new quality of end-of-life care instrument as a mechanism for evaluative
      feedback to health professionals, health systems, and policy makers to improve
      children's end-of-life care.

PMID- 25620885
TI  - Shift work to balance everyday life - a salutogenic nursing perspective in home
      help service in Sweden.
AB  - BACKGROUND: Nurses in Sweden have a high absence due to illness and many retire
      before the age of sixty. Factors at work as well as in private life may
      contribute to health problems. To maintain a healthy work-force there is a need
      for actions on work-life balance in a salutogenic perspective. The aim of this
      study was to explore perceptions of resources in everyday life to balance work
      and private life among nurses in home help service. METHODS: Thirteen semi
      structured individual interviews and two focus group interviews were conducted
      with home help service nurses in Sweden. A qualitative content analysis was used
      for the analyses. RESULT: In the analyses, six themes of perceptions of recourses
      in everyday life emerged; (i) Reflecting on life. (ii) Being healthy and taking
      care of yourself. (iii) Having a meaningful job and a supportive work climate.
      (iv) Working shifts and part time. (v) Having a family and a supporting network.
      (vi) Making your home your castle. CONCLUSIONS: The result points out the
      complexity of work-life balance and support that the need for nurses to balance
      everyday life differs during different phases and transitions in life. In this
      salutogenic study, the result differs from studies with a pathogenic approach.
      Shift work and part time work were seen as two resources that contributed to
      flexibility and a prerequisite to work-life balance. To have time and energy for
      both private life and work was seen as essential. To reflect on and discuss life
      gave inner strength to set boundaries and to prioritize both in private life and
      in work life. Managers in nursing contexts have a great challenge to maintain and
      strengthen resources which enhance the work-life balance and health of nurses.
      Salutogenic research is needed to gain an understanding of resources that enhance
      work-life balance and health in nursing contexts.

PMID- 25620886
TI  - The Discrimination of Printed Words by Prereading Children.
AB  - In addition to the discrimination of individual printed letters, beginning
      readers must learn to perceive individual letters within complex, whole-word
      stimuli. The present study shows that the discrimination of letters presented
      individually does not automatically entail the discrimination of 3-letter printed
      words that differ only in the first letter (e.g., sat, mat). Thirty-two children
      ranging in age from 31/2 to 51/2 years participated in two studies. All showed
      highly accurate discrimination of individual letters in identity matching-to
      sample procedures before being exposed to the word-matching task. On the word
      matching task, 21 of the 32 children showed accuracy of less than 85%, and 11 of
      these showed accuracy of 65% or less. Word-discrimination accuracy did not
      improve in retests of a subset of children after periods ranging from 3 weeks to
      3 months. In Study 2, six children who initially showed relatively low word
      matching accuracy were taught using fading procedures. Moreover, generalization
      to untaught words was shown. These results extend basic laboratory studies that
      have shown difficulties discriminating multi-element stimuli despite the
      discrimination of the individual component elements.

PMID- 25620887
TI  - Immigration to the United States: Recent Trends and Future Prospects.
AB  - Almost 13 per cent of the American population is foreign born, and if the
      children of the foreign born are included, about 1 in 4 Americans can be counted
      as part of the recent immigrant community. Although there is lingering prejudice
      and popular fears of immigrants, there is growing evidence that, on balance,
      immigrants make a positive contribution to the American economy and society.
      There is little evidence that immigrants have an adverse impact on the wages and
      employment of native born Americans. Moreover, immigrants and their children are
      disproportionately represented in a broad variety of scientific and cultural
      fields.

PMID- 25620888
TI  - Differences in Reliability of Reproductive History Recall Among Women in North
      Africa.
AB  - Breast cancer is the most common cancer among women in North Africa. Women in
      this region have unique reproductive profiles. It is essential to obtain reliable
      information on reproductive histories to help better understand the relationship
      between reductive health and breast cancer. We tested the reliability of a
      reproductive history-based questionnaire. We interviewed 25 breast cancer
      patients and 25 non-cancer controls from hospitals in Morocco and Egypt about
      their reproductive history in colloquial Arabic. The questions included pregnancy
      history, breastfeeding practices, menstruation, contraceptive use and knowledge
      of breast screening and re-interviewed the same women after 2 weeks. Two-way
      paired t-test was used to compare observed mean changes in response, and the
      Fishers Exact test was used for small-cell data. Pearson's correlation test was
      used to estimate the correlation of subjects' responses to continuous questions
      between the first and second interview. For categorical questions, percentage of
      agreement was calculated along with Cohen's Kappa Coefficient values. Moroccan
      subjects showed good to excellent agreement for responses to all demographic and
      reproductive questions (r = 0.87 to 0.99). Egyptian subjects had excellent
      agreement for these questions(r = 0.87 to 0.99), except for those regarding
      duration of oral contraceptive pill use and reported age at menarche (r = 0.72
      and 0.59, respectively). We showed highly correlated responses to most
      reproductive questions. Duration of contraception use and age at first pregnancy
      elicited slightly less than reliable responses. In Egypt, responses relating to
      self-reported age at menarche were less reliable than those given by Moroccan
      subjects. Future epidemiological studies should take these differences into
      account when constructing reproductive history questionnaires.

PMID- 25620889
TI  - Experimental Evidence That Low Social Status is Most Toxic to Well-being When
      Internalized.
AB  - What makes low social status toxic to well-being? To internalize social status is
      to believe the self is responsible for it. We hypothesized that the more people
      internalize low subjective social status, the more their basic psychological
      needs are thwarted. Experiment 1 randomly assigned participants to imagine
      themselves in low, middle, or high social status and assessed their subjective
      social status internalization by independent ratings. The more participants
      internalized low status, the more they reported their basic psychological needs
      were thwarted. This effect did not appear among their higher status counterparts.
      Experiment 2 replicated and extended these findings using a behavioral
      manipulation of subjective social status and a self-report measure of
      internalization. We discuss implications for basic and action research.

PMID- 25620890
TI  - The fastclime Package for Linear Programming and Large-Scale Precision Matrix
      Estimation in R.
AB  - We develop an R package fastclime for solving a family of regularized linear
      programming (LP) problems. Our package efficiently implements the parametric
      simplex algorithm, which provides a scalable and sophisticated tool for solving
      large-scale linear programs. As an illustrative example, one use of our LP solver
      is to implement an important sparse precision matrix estimation method called
      CLIME (Constrained L1 Minimization Estimator). Compared with existing packages
      for this problem such as clime and flare, our package has three advantages: (1)
      it efficiently calculates the full piecewise-linear regularization path; (2) it
      provides an accurate dual certificate as stopping criterion; (3) it is completely
      coded in C and is highly portable. This package is designed to be useful to
      statisticians and machine learning researchers for solving a wide range of
      problems.

PMID- 25620891
TI  - Learning Graphical Models With Hubs.
AB  - We consider the problem of learning a high-dimensional graphical model in which
      there are a few hub nodes that are densely-connected to many other nodes. Many
      authors have studied the use of an l1 penalty in order to learn a sparse graph in
      the high-dimensional setting. However, the l1 penalty implicitly assumes that
      each edge is equally likely and independent of all other edges. We propose a
      general framework to accommodate more realistic networks with hub nodes, using a
      convex formulation that involves a row-column overlap norm penalty. We apply this
      general framework to three widely-used probabilistic graphical models: the
      Gaussian graphical model, the covariance graph model, and the binary Ising model.
      An alternating direction method of multipliers algorithm is used to solve the
      corresponding convex optimization problems. On synthetic data, we demonstrate
      that our proposed framework outperforms competitors that do not explicitly model
      hub nodes. We illustrate our proposal on a webpage data set and a gene expression
      data set.

PMID- 25620892
TI  - Graph Estimation From Multi-Attribute Data.
AB  - Undirected graphical models are important in a number of modern applications that
      involve exploring or exploiting dependency structures underlying the data. For
      example, they are often used to explore complex systems where connections between
      entities are not well understood, such as in functional brain networks or genetic
      networks. Existing methods for estimating structure of undirected graphical
      models focus on scenarios where each node represents a scalar random variable,
      such as a binary neural activation state or a continuous mRNA abundance
      measurement, even though in many real world problems, nodes can represent
      multivariate variables with much richer meanings, such as whole images, text
      documents, or multi-view feature vectors. In this paper, we propose a new
      principled framework for estimating the structure of undirected graphical models
      from such multivariate (or multi-attribute) nodal data. The structure of a graph
      is inferred through estimation of non-zero partial canonical correlation between
      nodes. Under a Gaussian model, this strategy is equivalent to estimating
      conditional independencies between random vectors represented by the nodes and it
      generalizes the classical problem of covariance selection (Dempster, 1972). We
      relate the problem of estimating non-zero partial canonical correlations to
      maximizing a penalized Gaussian likelihood objective and develop a method that
      efficiently maximizes this objective. Extensive simulation studies demonstrate
      the effectiveness of the method under various conditions. We provide illustrative
      applications to uncovering gene regulatory networks from gene and protein
      profiles, and uncovering brain connectivity graph from positron emission
      tomography data. Finally, we provide sufficient conditions under which the true
      graphical structure can be recovered correctly.

PMID- 25620893
TI  - MONOMIALS AND BASIN CYLINDERS FOR NETWORK DYNAMICS.
AB  - We describe methods to identify cylinder sets inside a basin of attraction for
      Boolean dynamics of biological networks. Such sets are used for designing
      regulatory interventions that make the system evolve towards a chosen attractor,
      for example initiating apoptosis in a cancer cell. We describe two algebraic
      methods for identifying cylinders inside a basin of attraction, one based on the
      Groebner fan that finds monomials that define cylinders and the other on primary
      decomposition. Both methods are applied to current examples of gene networks.

PMID- 25620894
TI  - Emerging Novel Treatments for Severe Mood Disorders Involving Cellular Plasticity
      Cascades.
AB  - Mood disorders are the most prevalent psychiatric disorders. Despite recent
      advances in the understanding of therapeutically relevant biochemical pathways
      associated with mood regulation, patients with bipolar disorder and major
      depression present high rates of recurrences, residual symptoms, and
      pharmacologic refractoriness. Increasing evidence supports the observations that
      mood disorders are accompanied by regional brain volumetric reductions
      accompanied by cellular atrophy/loss. In this paper, we review and critique the
      data suggesting that neurotrophic signaling cascades may play a role in the
      pathophysiology and treatment of mood disorders. This suggests that effective
      treatments will need to provide both trophic and neurochemical support, which
      serves to enhance and maintain normal synaptic connectivity, thereby allowing the
      chemical signal to reinstate optimal functioning of critical circuits necessary
      for normal affective functioning. For many refractory patients, drugs mimicking
      "traditional" strategies, which directly or indirectly alter monoaminergic
      levels, may be of limited benefit. Newer "plasticity enhancing" strategies that
      may have utility in the treatment of mood disorders include inhibitors of
      glutamate release, NMDA antagonists, AMPA potentiators, cAMP phosphodiesterase
      inhibitors, and glucocorticoid receptor antagonists.

PMID- 25620895
TI  - Predicting protein backbone chemical shifts from Calpha coordinates: extracting
      high resolution experimental observables from low resolution models.
AB  - Given the demonstrated utility of coarse-grained modeling and simulations
      approaches in studying protein structure and dynamics, developing methods that
      allow experimental observables to be directly recovered from coarse-grained
      models is of great importance. In this work, we develop one such method that
      enables protein backbone chemical shifts (1HN, 1Halpha, 13Calpha, 13C, 13Cbeta,
      and 15N) to be predicted from Calpha coordinates. We show that our Calpha-based
      method, LARMORCalpha, predicts backbone chemical shifts with comparable accuracy
      to some all-atom approaches. More importantly, we demonstrate that LARMORCalpha
      predicted chemical shifts are able to resolve native structure from decoy pools
      that contain both native and non-native models, and so it is sensitive to protein
      structure. As an application, we use LARMORCalpha to characterize the transient
      state of the fast-folding protein gpW using recently published NMR relaxation
      dispersion derived backbone chemical shifts. The model we obtain is consistent
      with the previously proposed model based on independent analysis of the chemical
      shift dispersion pattern of the transient state. We anticipate that LARMORCalpha
      will find utility as a tool that enables important protein conformational
      substates to be identified by "parsing" trajectories and ensembles generated
      using coarse-grained modeling and simulations.

PMID- 25620896
TI  - Density-biased sampling: a robust computational method for studying pore
      formation in membranes.
AB  - A new reaction coordinate to bias molecular dynamics simulation is described that
      allows enhanced sampling of density-driven processes, such as mixing and demixing
      two different molecular species. The methodology is validated by comparing the
      theoretical entropy of demixing two ideal gas species and then applied to induce
      deformation and pore formation in phospholipid membranes within an umbrella
      sampling framework. Comparison with previous biased simulations of membrane pore
      formation suggests overall quantitative agreement, but the density-based biasing
      potential results in a different, more realistic transition pathway than that in
      previous studies.

PMID- 25620897
TI  - Identification of Plasmonic Modes in Parabolic Cylinder Geometry by Quasi
      Separation of Variables.
AB  - This paper describes the plasmonic modes in the parabolic cylinder geometry as a
      theoretical complement to the previous paper (J Phys A 42:185401) that considered
      the modes in the circular paraboloidal geometry. In order to identify the
      plasmonic modes in the parabolic cylinder geometry, analytic solutions for
      surface plasmon polaritons are examined by solving the wave equation for the
      magnetic field in parabolic cylindrical coordinates using quasi-separation of
      variables in combination with perturbation methods. The examination of the zeroth
      order perturbation equations showed that solutions cannot exist for the parabolic
      metal wedge but can be obtained for the parabolic metal groove as standing wave
      solutions indicated by the even and odd symmetries.

PMID- 25620898
TI  - Generation of Regulatory T Cells to Antigen Expressed in the Retina.
AB  - Regulatory T cells (Tregs) are generated to antigens (Ag) found in the retina.
      Some Tregs are the result of ectopic expression of the retinal Ags in the thymus,
      where developing T cells are committed to enter the regulatory lineage. However,
      the generation of retinal Ag-specific Tregs independent of the thymus was
      uncertain. Our studies show that Tregs can be generated from mature, peripheral T
      cells based on exposure to retinal Ags. These peripherally induced Tregs limited
      immune responses and experimental autoimmune disease induced by retinal Ags and
      thus constitute a crucial component of retinal immune privilege.

PMID- 25620899
TI  - PSYCHIATRIC DISORDERS ASSOCIATED WITH FXTAS.
AB  - Carriers of the FMR1 premutation (with 55-200 CGG repeats) may present with
      multiple medical and psychiatric disorders. Middle-aged carriers (males more
      often than females) may suffer from fragile X-associated tremor/ataxia syndrome
      (FXTAS). FXTAS is a newly discovered neurodegenerative disease characterized by
      intention tremor and ataxia, along with several other neurological features.
      Psychiatric manifestations are common in premutation carriers of both genders and
      include attention deficits, anxiety, depression, irritability, impulse
      dyscontrol, and substance abuse or dependence. Major depressive disorder, panic
      disorder with or without agoraphobia, generalized anxiety disorder, social
      phobia, and specific phobia are among the psychiatric diagnoses often encountered
      in premutation carriers, including those with FXTAS. Later in the course of the
      illness, cognitive deficits (including dementia) may occur. In this paper, we
      discuss common psychiatric phenotypes in FXTAS, based on a thorough review of the
      literature, as well as our own research experience. Symptomatic pharmacologic
      treatments are available, although disease modifying agents have not yet been
      developed.

PMID- 25620900
TI  - Postpartum Depression in Women with the FMR1 Premutation.
AB  - BACKGROUND: Psychiatric disorders in women with the FMR1 premutation are common
      and include attention deficit hyperactivity disorder, anxiety, depression, and
      eating disorders. This pilot study explored the risk factors for postpartum
      depression (PPD) in women with the premutation. METHODS: We conducted a chart
      review of 50 women premutation carriers with major depressive disorder who had
      children. Of these, 7 women had a history of major depressive episodes in the
      postpartum period. The PPD and non-PPD groups were characterized descriptively
      based on women's age at the time of the psychiatric evaluation, race, ethnicity,
      education level, IQ, CGG repeat size, comorbid psychiatric conditions, parity,
      and number of children with fragile X syndrome (FXS). Exact logistic regression
      was used to analyze the relationship between the number of children with FXS and
      the risk of PPD. RESULTS: The PPD and non-PPD groups were similar on all
      variables examined, with the exception of the number of affected children. Each
      of the 7 women with PPD had at least one child with FXS, whereas a third of the
      women without PPD had no affected children. For each additional affected child,
      the risk of PPD increased by 158% (exact odds ratio 2.58, 95% CI 0.99-7.59).
      Further studies are needed to replicate these findings and to better characterize
      PPD in female premutation carriers.

PMID- 25620901
TI  - COGNITIVE DYSFUNCTION IN FMR1 PREMUTATION CARRIERS.
AB  - Premutation carriers of the fragile X mental retardation gene (especially men)
      older than 50 may develop a neurodegenerative disease, the fragile X-associated
      tremor/ataxia syndrome (FXTAS). Carriers may present with varied cognitive
      impairments. Attention, working memory, declarative and procedural learning,
      information processing speed, and recall are among the cognitive domains
      affected. Executive dysfunction is a prominent deficit, which has been
      demonstrated mostly in men with FXTAS. In more advanced stages of FXTAS, both men
      and women may develop a mixed cortical-subcortical dementia, manifested by
      psychomotor slowing and deficits in attention, retrieval, recall, visuospatial
      skills, occasional apraxia, as well as overt personality changes. Studies have
      shown dementia rates as high as 37-42% in older men with FXTAS, although more
      research is needed to understand the prevalence and risk factors of dementia in
      women with FXTAS. Neuropsychiatric symptoms are common and reflect the
      dysfunction of underlying frontal-subcortical neural circuits, along with
      components of the cerebellar cognitive affective syndrome. These include labile
      or depressed mood, anxiety, disinhibition, impulsivity, and (rarely) psychotic
      symptoms. In this paper we review the information available to date regarding the
      prevalence and clinical picture of FXTAS dementia. Differential diagnosis may be
      difficult, given overlapping motor and non-motor signs with several other
      neurodegenerative diseases. Anecdotal response to cholinesterase inhibitors and
      memantine has been reported, while symptomatic treatments can address the
      neuropsychiatric manifestations of FXTAS dementia.

PMID- 25620902
TI  - 3D-resolved targeting of photodynamic therapy using temporal focusing.
AB  - A method for selectively inducing apoptosis in tumor nodules is presented, with
      close-to-cellular level resolution, using 3D-resolved widefield temporal focusing
      illumination. Treatment times on the order of seconds were achieved using
      Verteporfin as the photosensitizer, with doses of 30 MUg ml-1 and below. Results
      were achieved on both 2D and 3D cell cultures, demonstrating that treatment was
      possible through approximately one hundred microns of dense tumor nodules.

PMID- 25620903
TI  - Guidelines for Diagnosis and Treatment of Carcinoma of the Esophagus April 2012
      edited by the Japan Esophageal Society.

PMID- 25620904
TI  - Esophageal metastasis of renal cancer 10 years after nephrectomy.
AB  - The patient was a 65-year-old man, who had undergone right nephrectomy for renal
      cancer in 2002. At that time, histopathological examination revealed clear cell
      carcinoma (pT3a, pN0, M0, and pStage III). Postoperatively, he received natural
      interferon alpha (6 million units 3 times a week) from November 2002 to February
      2005, and showed no evidence of recurrence. However, he noticed dysphagia in
      March 2012. Endoscopy revealed a pedunculated polypoid tumor in the mid-esophagus
      and biopsies were taken showing a clear cell carcinoma. Contrast-enhanced
      thoracoabdominal CT scanning identified a pedunculated polypoid tumor in the mid
      thoracic esophagus and enlargement of a lymph node adjacent to the right main
      bronchus. With a diagnosis of esophageal and lymph node metastases of renal
      cancer, the patient underwent esophagectomy with right thoracotomy with
      reconstruction by a posterior mediastinal stomach tube. Postoperative
      histopathological examination revealed clear cell carcinoma. Because esophageal
      metastasis of renal cancer is extremely rare, this case is reported here together
      with discussions of the relevant literature.

PMID- 25620905
TI  - Electronic cigarettes: overview of chemical composition and exposure estimation.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) are advertised to tobacco users
      as a tool to decrease cigarette consumption and to reduce toxic exposure
      associated with conventional tobacco smoking. Little is known about the compounds
      contained in such products, their exposure and long-term health effects. METHODS:
      NMR spectroscopy was used to ascertain the content of several constituents of e
      cigarette liquids including nicotine, solvents and some bioactive flavour
      compounds. Risk assessment was based on probabilistic exposure estimation and
      comparison with toxicological thresholds using the margin of exposure (MOE)
      approach. RESULTS: In 54 samples of e-cigarette liquids, the average nicotine
      content was 11 mg/ml. Only 18 from 23 samples were confirmed as nicotine-free
      samples and in one e-cigarette liquid nicotine was not detected while being
      declared on the labelling. Major compounds of e-cigarette liquids include
      glycerol (average 37 g/100 g), propylene glycol (average 57 g/100 g) and ethylene
      glycol (average 10 g/100 g). Furthermore, 1,3-propanediol, thujone and ethyl
      vanillin were detected in some samples. The average exposure for daily users was
      estimated as 0.38 mg/kg bw/day for nicotine, 8.9 mg/kg bw/day for glycerol, 14.5
      mg/kg bw/day for 1,2-propanediol, 2.1 mg/kg bw/day for ethylene glycol, and below
      0.2 mg/kg bw/day for the other compounds. The MOE was below 0.1 for nicotine, but
      all other compounds did not reach MOE values below 100 except ethylene glycol and
      1,2-propanediol. CONCLUSIONS: NMR spectroscopy is a useful and rapid method to
      simultaneously detect several ingredients in e-cigarette liquids. From all
      compounds tested, only nicotine may reach exposures that fall into a high risk
      category with MOE <1. Therefore, e-cigarette liquid products should be subjected
      to regulatory control to ensure consistent nicotine delivery. Solvents with more
      favourable toxicological profiles should be used instead of ethylene glycol and
      1,2-propanediol, which may fall into a risk category with MOE < 100.

PMID- 25620906
TI  - High-resolution diffusion kurtosis imaging at 3T enabled by advanced post
      processing.
AB  - Diffusion Kurtosis Imaging (DKI) is more sensitive to microstructural differences
      and can be related to more specific micro-scale metrics (e.g., intra-axonal
      volume fraction) than diffusion tensor imaging (DTI), offering exceptional
      potential for clinical diagnosis and research into the white and gray matter.
      Currently DKI is acquired only at low spatial resolution (2-3 mm isotropic),
      because of the lower signal-to-noise ratio (SNR) and higher artifact level
      associated with the technically more demanding DKI. Higher spatial resolution of
      about 1 mm is required for the characterization of fine white matter pathways or
      cortical microstructure. We used restricted-field-of-view (rFoV) imaging in
      combination with advanced post-processing methods to enable unprecedented high
      quality, high-resolution DKI (1.2 mm isotropic) on a clinical 3T scanner. Post
      processing was advanced by developing a novel method for Retrospective Eddy
      current and Motion ArtifacT Correction in High-resolution, multi-shell diffusion
      data (REMATCH). Furthermore, we applied a powerful edge preserving denoising
      method, denoted as multi-shell orientation-position-adaptive smoothing (msPOAS).
      We demonstrated the feasibility of high-quality, high-resolution DKI and its
      potential for delineating highly myelinated fiber pathways in the motor cortex.
      REMATCH performs robustly even at the low SNR level of high-resolution DKI, where
      standard EC and motion correction failed (i.e., produced incorrectly aligned
      images) and thus biased the diffusion model fit. We showed that the combination
      of REMATCH and msPOAS increased the contrast between gray and white matter in
      mean kurtosis (MK) maps by about 35% and at the same time preserves the original
      distribution of MK values, whereas standard Gaussian smoothing strongly biases
      the distribution. 

PMID- 25620907
TI  - Central control of autonomic functions in health and disease.

PMID- 25620908
TI  - Computational deconvolution of genome wide expression data from Parkinson's and
      Huntington's disease brain tissues using population-specific expression analysis.
AB  - The characterization of molecular changes in diseased tissues gives insight into
      pathophysiological mechanisms and is important for therapeutic development.
      Genome-wide gene expression analysis has proven valuable for identifying
      biological processes in neurodegenerative diseases using post mortem human brain
      tissue and numerous datasets are publically available. However, many studies
      utilize heterogeneous tissue samples consisting of multiple cell types, all of
      which contribute to global gene expression values, confounding biological
      interpretation of the data. In particular, changes in numbers of neuronal and
      glial cells occurring in neurodegeneration confound transcriptomic analyses,
      particularly in human brain tissues where sample availability and controls are
      limited. To identify cell specific gene expression changes in neurodegenerative
      disease, we have applied our recently published computational deconvolution
      method, population specific expression analysis (PSEA). PSEA estimates cell-type
      specific expression values using reference expression measures, which in the case
      of brain tissue comprises mRNAs with cell-type-specific expression in neurons,
      astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation
      and hypothesis development regarding neurodegenerative diseases, we applied PSEA
      to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as
      differentially expressed in substantia nigra pars compacta neurons by PSEA were
      validated using external laser capture microdissection data. Network analysis and
      Annotation Clustering (DAVID) identified molecular processes implicated by
      differential gene expression in specific cell types. The results of these
      analyses provided new insights into the implementation of PSEA in brain tissues
      and additional refinement of molecular signatures in human HD and PD. 

PMID- 25620910
TI  - CHIP, a carboxy terminus HSP-70 interacting protein, prevents cell death induced
      by endoplasmic reticulum stress in the central nervous system.
AB  - Endoplasmic reticulum (ER) stress and protein misfolding are associated with
      various neurodegenerative diseases. ER stress activates unfolded protein response
      (UPR), an adaptative response. However, severe ER stress can induce cell death.
      Here we show that the E3 ubiquitin ligase and co-chaperone Carboxyl Terminus
      HSP70/90 Interacting Protein (CHIP) prevents neuron death in the hippocampus
      induced by severe ER stress. Organotypic hippocampal slice cultures (OHSCs) were
      exposed to Tunicamycin, a pharmacological ER stress inducer, to trigger cell
      death. Overexpression of CHIP was achieved with a recombinant adeno-associated
      viral vector (rAAV) and significantly diminished ER stress-induced cell death, as
      shown by analysis of propidium iodide (PI) uptake, condensed chromatin, TUNEL and
      cleaved caspase 3 in the CA1 region of OHSCs. In addition, overexpression of CHIP
      prevented upregulation of both CHOP and p53 both pro-apoptotic pathways induced
      by ER stress. We also detected an attenuation of eIF2a phosphorylation promoted
      by ER stress. However, CHIP did not prevent upregulation of BiP/GRP78 induced by
      UPR. These data indicate that overexpression of CHIP attenuates ER-stress death
      response while maintain ER stress adaptative response in the central nervous
      system. These results indicate a neuroprotective role for CHIP upon UPR
      signaling. CHIP emerge as a candidate for clinical intervention in
      neurodegenerative diseases associated with ER stress. 

PMID- 25620909
TI  - The interplay of early-life stress, nutrition, and immune activation programs
      adult hippocampal structure and function.
AB  - Early-life adversity increases the vulnerability to develop psychopathologies and
      cognitive decline later in life. This association is supported by clinical and
      preclinical studies. Remarkably, experiences of stress during this sensitive
      period, in the form of abuse or neglect but also early malnutrition or an early
      immune challenge elicit very similar long-term effects on brain structure and
      function. During early-life, both exogenous factors like nutrition and maternal
      care, as well as endogenous modulators, including stress hormones and mediator of
      immunological activity affect brain development. The interplay of these key
      elements and their underlying molecular mechanisms are not fully understood. We
      discuss here the hypothesis that exposure to early-life adversity (specifically
      stress, under/malnutrition and infection) leads to life-long alterations in
      hippocampal-related cognitive functions, at least partly via changes in
      hippocampal neurogenesis. We further discuss how these different key elements of
      the early-life environment interact and affect one another and suggest that it is
      a synergistic action of these elements that shapes cognition throughout life.
      Finally, we consider different intervention studies aiming to prevent these early
      life adversity induced consequences. The emerging evidence for the intriguing
      interplay of stress, nutrition, and immune activity in the early-life programming
      calls for a more in depth understanding of the interaction of these elements and
      the underlying mechanisms. This knowledge will help to develop intervention
      strategies that will converge on a more complete set of changes induced by early
      life adversity. 

PMID- 25620911
TI  - Pleiotrophin as a central nervous system neuromodulator, evidences from the
      hippocampus.
AB  - Pleiotrophin (PTN) is a secreted growth factor, and also a cytokine, associated
      with the extracellular matrix, which has recently starting to attract attention
      as a significant neuromodulator with multiple neuronal functions during
      development. PTN is expressed in several tissues, where its signals are generally
      related with cell proliferation, growth, and differentiation by acting through
      different receptors. In Central Nervous System (CNS), PTN exerts post
      developmental neurotrophic and -protective effects, and additionally has been
      involved in neurodegenerative diseases and neural disorders. Studies in
      Drosophila shed light on some aspects of the different levels of regulatory
      control of PTN invertebrate homologs. Specifically in hippocampus, recent
      evidence from PTN Knock-out (KO) mice involves PTN functioning in learning and
      memory. In this paper, we summarize, discuss, and contrast the most recent
      advances and results that lead to proposing a PTN as a neuromodulatory molecule
      in the CNS, particularly in hippocampus. 

PMID- 25620912
TI  - Parvalbumin and neuropeptide Y expressing hippocampal GABA-ergic inhibitory
      interneuron numbers decline in a model of Gulf War illness.
AB  - Cognitive dysfunction is amongst the most conspicuous symptoms in Gulf War
      illness (GWI). Combined exposure to the nerve gas antidote pyridostigmine bromide
      (PB), pesticides and stress during the Persian Gulf War-1 (PGW-1) are presumed to
      be among the major causes of GWI. Indeed, our recent studies in rat models have
      shown that exposure to GWI-related (GWIR) chemicals and mild stress for 4 weeks
      engenders cognitive impairments accompanied with several detrimental changes in
      the hippocampus. In this study, we tested whether reduced numbers of hippocampal
      gamma-amino butyric acid (GABA)-ergic interneurons are among the pathological
      changes induced by GWIR-chemicals and stress. Animals were exposed to low doses
      of GWIR-chemicals and mild stress for 4 weeks. Three months after this exposure,
      subpopulations of GABA-ergic interneurons expressing the calcium binding protein
      parvalbumin (PV), the neuropeptide Y (NPY) and somatostatin (SS) in the
      hippocampus were stereologically quantified. Animals exposed to GWIR-chemicals
      and stress for 4 weeks displayed reduced numbers of PV-expressing GABA-ergic
      interneurons in the dentate gyrus and NPY-expressing interneurons in the CA1 and
      CA3 subfields. However, no changes in SS+ interneuron population were observed in
      the hippocampus. Furthermore, GABA-ergic interneuron deficiency in these animals
      was associated with greatly diminished hippocampus neurogenesis. Because PV+ and
      NPY+ interneurons play roles in maintaining normal cognitive function and
      neurogenesis, and controlling the activity of excitatory neurons in the
      hippocampus, reduced numbers of these interneurons may be one of the major causes
      of cognitive dysfunction and reduced neurogenesis observed in GWI. Hence,
      strategies that improve inhibitory neurotransmission in the hippocampus may prove
      beneficial for reversing cognitive dysfunction in GWI. 

PMID- 25620913
TI  - Subthreshold membrane currents confer distinct tuning properties that enable
      neurons to encode the integral or derivative of their input.
AB  - Neurons rely on action potentials, or spikes, to encode information. But spikes
      can encode different stimulus features in different neurons. We show here through
      simulations and experiments how neurons encode the integral or derivative of
      their input based on the distinct tuning properties conferred upon them by
      subthreshold currents. Slow-activating subthreshold inward (depolarizing) current
      mediates positive feedback control of subthreshold voltage, sustaining
      depolarization and allowing the neuron to spike on the basis of its integrated
      stimulus waveform. Slow-activating subthreshold outward (hyperpolarizing) current
      mediates negative feedback control of subthreshold voltage, truncating
      depolarization and forcing the neuron to spike on the basis of its differentiated
      stimulus waveform. Depending on its direction, slow-activating subthreshold
      current cooperates or competes with fast-activating inward current during spike
      initiation. This explanation predicts that sensitivity to the rate of change of
      stimulus intensity differs qualitatively between integrators and differentiators.
      This was confirmed experimentally in spinal sensory neurons that naturally behave
      as specialized integrators or differentiators. Predicted sensitivity to different
      stimulus features was confirmed by covariance analysis. Integration and
      differentiation, which are themselves inverse operations, are thus shown to be
      implemented by the slow feedback mediated by oppositely directed subthreshold
      currents expressed in different neurons. 

PMID- 25620914
TI  - Visual cortical areas of the mouse: comparison of parcellation and network
      structure with primates.
AB  - Brains have evolved to optimize sensory processing. In primates, complex
      cognitive tasks must be executed and evolution led to the development of large
      brains with many cortical areas. Rodents do not accomplish cognitive tasks of the
      same level of complexity as primates and remain with small brains both in
      relative and absolute terms. But is a small brain necessarily a simple brain? In
      this review, several aspects of the visual cortical networks have been compared
      between rodents and primates. The visual system has been used as a model to
      evaluate the level of complexity of the cortical circuits at the anatomical and
      functional levels. The evolutionary constraints are first presented in order to
      appreciate the rules for the development of the brain and its underlying
      circuits. The organization of sensory pathways, with their parallel and cross
      modal circuits, is also examined. Other features of brain networks, often
      considered as imposing constraints on the development of underlying circuitry,
      are also discussed and their effect on the complexity of the mouse and primate
      brain are inspected. In this review, we discuss the common features of cortical
      circuits in mice and primates and see how these can be useful in understanding
      visual processing in these animals. 

PMID- 25620915
TI  - Evolution of mammalian sensorimotor cortex: thalamic projections to parietal
      cortical areas in Monodelphis domestica.
AB  - The current experiments build upon previous studies designed to reveal the
      network of parietal cortical areas present in the common mammalian ancestor.
      Understanding this ancestral network is essential for highlighting the basic
      somatosensory circuitry present in all mammals, and how this basic plan was
      modified to generate species specific behaviors. Our animal model, the short
      tailed opossum (Monodelphis domestica), is a South American marsupial that has
      been proposed to have a similar ecological niche and morphology to the earliest
      common mammalian ancestor. In this investigation, we injected retrograde
      neuroanatomical tracers into the face and body representations of primary
      somatosensory cortex (S1), the rostral and caudal somatosensory fields (SR and
      SC), as well as a multimodal region (MM). Projections from different
      architectonically defined thalamic nuclei were then quantified. Our results
      provide further evidence to support the hypothesized basic mammalian plan of
      thalamic projections to S1, with the lateral and medial ventral posterior
      thalamic nuclei (VPl and VPm) projecting to S1 body and S1 face, respectively.
      Additional strong projections are from the medial division of posterior nucleus
      (Pom). SR receives projections from several midline nuclei, including the medial
      dorsal, ventral medial nucleus, and Pom. SC and MM show similar patterns of
      connectivity, with projections from the ventral anterior and ventral lateral
      nuclei, VPm and VPl, and the entire posterior nucleus (medial and lateral).
      Notably, MM is distinguished from SC by relatively dense projections from the
      dorsal division of the lateral geniculate nucleus and pulvinar. We discuss the
      finding that S1 of the short-tailed opossum has a similar pattern of projections
      as other marsupials and mammals, but also some distinct projections not present
      in other mammals. Further we provide additional support for a primitive posterior
      parietal cortex which receives input from multiple modalities. 

PMID- 25620916
TI  - How to build better memory training games.
AB  - Can we create engaging training programs that improve working memory (WM) skills?
      While there are numerous procedures that attempt to do so, there is a great deal
      of controversy regarding their efficacy. Nonetheless, recent meta-analytic
      evidence shows consistent improvements across studies on lab-based tasks
      generalizing beyond the specific training effects (Au et al., 2014; Karbach and
      Verhaeghen, 2014), however, there is little research into how WM training aids
      participants in their daily life. Here we propose that incorporating design
      principles from the fields of Perceptual Learning (PL) and Computer Science might
      augment the efficacy of WM training, and ultimately lead to greater learning and
      transfer. In particular, the field of PL has identified numerous mechanisms
      (including attention, reinforcement, multisensory facilitation and multi-stimulus
      training) that promote brain plasticity. Also, computer science has made great
      progress in the scientific approach to game design that can be used to create
      engaging environments for learning. We suggest that approaches integrating
      knowledge across these fields may lead to a more effective WM interventions and
      better reflect real world conditions. 

PMID- 25620918
TI  - Control of humanoid robot via motion-onset visual evoked potentials.
AB  - This paper investigates controlling humanoid robot behavior via motion-onset
      specific N200 potentials. In this study, N200 potentials are induced by moving a
      blue bar through robot images intuitively representing robot behaviors to be
      controlled with mind. We present the individual impact of each subject on N200
      potentials and discuss how to deal with individuality to obtain a high accuracy.
      The study results document the off-line average accuracy of 93% for hitting
      targets across over five subjects, so we use this major component of the motion
      onset visual evoked potential (mVEP) to code people's mental activities and to
      perform two types of on-line operation tasks: navigating a humanoid robot in an
      office environment with an obstacle and picking-up an object. We discuss the
      factors that affect the on-line control success rate and the total time for
      completing an on-line operation task. 

PMID- 25620917
TI  - Neurons containing orexin or melanin concentrating hormone reciprocally regulate
      wake and sleep.
AB  - Neurons containing orexin (hypocretin), or melanin concentrating hormone (MCH)
      are intermingled with each other in the perifornical and lateral hypothalamus.
      Each is a separate and distinct neuronal population, but they project to similar
      target areas in the brain. Orexin has been implicated in regulating arousal since
      loss of orexin neurons is associated with the sleep disorder narcolepsy.
      Microinjections of orexin into the brain or optogenetic stimulation of orexin
      neurons increase waking. Orexin neurons are active in waking and quiescent in
      sleep, which is consistent with their role in promoting waking. On the other
      hand, the MCH neurons are quiet in waking but active in sleep, suggesting that
      they could initiate sleep. Recently, for the first time the MCH neurons were
      stimulated optogenetically and it increased sleep. Indeed, optogenetic activation
      of MCH neurons induced sleep in both mice and rats at a circadian time when they
      should be awake, indicating the powerful effect that MCH neurons have in
      suppressing the wake-promoting effect of not only orexin but also of all of the
      other arousal neurotransmitters. Gamma-Aminobutyric acid (GABA) is coexpressed
      with MCH in the MCH neurons, although MCH is also inhibitory. The inhibitory tone
      of the MCH neurons is opposite to the excitatory tone of the orexin neurons. We
      hypothesize that strength in activity of each determines wake vs. sleep. 

PMID- 25620920
TI  - Habituation mechanisms and their importance for cognitive function.

PMID- 25620919
TI  - Task, muscle and frequency dependent vestibular control of posture.
AB  - The vestibular system is crucial for postural control; however there are
      considerable differences in the task dependence and frequency response of
      vestibular reflexes in appendicular and axial muscles. For example, vestibular
      reflexes are only evoked in appendicular muscles when vestibular information is
      relevant to postural control, while in neck muscles they are maintained
      regardless of the requirement to maintain head on trunk balance. Recent
      investigations have also shown that the bandwidth of vestibular input on neck
      muscles is much broader than appendicular muscles (up to a factor of 3). This
      result challenges the notion that vestibular reflexes only contribute to postural
      control across the behavioral and physiological frequency range of the vestibular
      organ (i.e., 0-20 Hz). In this review, we explore and integrate these task-,
      muscle- and frequency-related differences in the vestibular system's contribution
      to posture, and propose that the human nervous system has adapted vestibular
      signals to match the mechanical properties of the system that each group of
      muscles controls. 

PMID- 25620921
TI  - Deficits of psychomotor and mnesic functions across aging in mouse lemur
      primates.
AB  - Owing to a similar cerebral neuro-anatomy, non-human primates are viewed as the
      most valid models for understanding cognitive deficits. This study evaluated
      psychomotor and mnesic functions of 41 young to old mouse lemurs (Microcebus
      murinus). Psychomotor capacities and anxiety-related behaviors decreased abruptly
      from middle to late adulthood. However, mnesic functions were not affected in the
      same way with increasing age. While results of the spontaneous alternation task
      point to a progressive and widespread age-related decline of spatial working
      memory, both spatial reference and novel object recognition (NOR) memory tasks
      did not reveal any tendency due to large inter-individual variability in the
      middle-aged and old animals. Indeed, some of the aged animals performed as well
      as younger ones, whereas some others had bad performances in the Barnes maze and
      in the object recognition test. Hierarchical cluster analysis revealed that
      declarative-like memory was strongly impaired only in 7 out of 25 middle-aged/old
      animals. These results suggest that this analysis allows to distinguish elder
      populations of good and bad performers in this non-human primate model and to
      closely compare this to human aging. 

PMID- 25620922
TI  - Drivers' decision-making when attempting to cross an intersection results from
      choice between affordances.
AB  - In theory, a safe approach to an intersection implies that drivers can
      simultaneously manage two scenarios: they either choose to cross or to give way
      to an oncoming vehicle. In this article we formalize the critical time for safe
      crossing (CT cross ) and the critical time for safe stopping (CT stop ) to
      represent crossing and stopping possibilities, respectively. We describe these
      critical times in terms of affordances and empirically test their respective
      contribution to the driver's decision-making process. Using a driving simulator,
      three groups of participants drove cars with identical acceleration capabilities
      and different braking capabilities. They were asked to try to cross an
      intersection where there was an oncoming vehicle, if they deemed the maneuver to
      be safe. If not, they could decide to stop or, as a last resort, make an
      emergency exit. The intersections were identical among groups. Results showed
      that although the crossing possibilities (CT cross ) were the same for all
      groups, there were between-group differences in crossing frequency. This suggests
      that stopping possibilities (CT stop ) play a role in the driver's decision
      making process, in addition to the crossing possibilities. These results can be
      accounted for by a behavioral model of decision making, and provide support for
      the hypothesis of choice between affordances. 

PMID- 25620924
TI  - An auditory multiclass brain-computer interface with natural stimuli: Usability
      evaluation with healthy participants and a motor impaired end user.
AB  - Brain-computer interfaces (BCIs) can serve as muscle independent communication
      aids. Persons, who are unable to control their eye muscles (e.g., in the
      completely locked-in state) or have severe visual impairments for other reasons,
      need BCI systems that do not rely on the visual modality. For this reason, BCIs
      that employ auditory stimuli were suggested. In this study, a multiclass BCI
      spelling system was implemented that uses animal voices with directional cues to
      code rows and columns of a letter matrix. To reveal possible training effects
      with the system, 11 healthy participants performed spelling tasks on 2
      consecutive days. In a second step, the system was tested by a participant with
      amyotrophic lateral sclerosis (ALS) in two sessions. In the first session,
      healthy participants spelled with an average accuracy of 76% (3.29 bits/min) that
      increased to 90% (4.23 bits/min) on the second day. Spelling accuracy by the
      participant with ALS was 20% in the first and 47% in the second session. The
      results indicate a strong training effect for both the healthy participants and
      the participant with ALS. While healthy participants reached high accuracies in
      the first session and second session, accuracies for the participant with ALS
      were not sufficient for satisfactory communication in both sessions. More
      training sessions might be needed to improve spelling accuracies. The study
      demonstrated the feasibility of the auditory BCI with healthy users and stresses
      the importance of training with auditory multiclass BCIs, especially for
      potential end-users of BCI with disease. 

PMID- 25620925
TI  - Is sham cTBS real cTBS? The effect on EEG dynamics.
AB  - Increasing sensitivity of modern evaluation tools allows for the study of weaker
      electric stimulation effects on neural populations. In the current study we
      examined the effects of sham continuous theta burst (cTBS) transcranial magnetic
      stimulation to the left dorsolateral prefrontal cortex (DLPFC) upon somatosensory
      evoked potentials (SEP) and frontal-parietal phase coupling of alpha and beta
      bands. Sham TMS results in an induced electric field amplitude roughly 5% that of
      real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced
      the amplitude of the frontal P14-N30 SEP and increased local phase coupling in
      the alpha-beta frequency bands of left frontal cortex. In addition, both sham and
      real cTBS increased frontal-parietal phase coupling in the alpha-beta bands
      concomitant with an increase in amplitude of parietal P50-N70 complex. These data
      suggest that weak electric fields from sham cTBS can affect both local and
      downstream neuronal circuits, though in a different manner than high strength
      TMS. 

PMID- 25620923
TI  - Development of thalamocortical connections between the mediodorsal thalamus and
      the prefrontal cortex and its implication in cognition.
AB  - The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the
      prefrontal cortex (PFC), and is thought to be highly implicated in modulation of
      cognitive performance. Additionally, it undergoes highly conserved developmental
      stages, which, when dysregulated, can have detrimental consequences.
      Embryonically, the MD experiences a tremendous surge in neurogenesis and
      differentiation, and disruption of this process may underlie the pathology in
      certain neurodevelopmental disorders. However, during the postnatal period, a
      vast amount of cell loss in the MD occurs. These together may represent an
      extended critical period for postnatal development, in which disturbances in the
      normal growth or reduction of the MD afferents to the PFC, can result in PFC
      dependent cognitive, affective, or psychotic abnormalities. In this review, we
      explore the current knowledge supporting this hypothesis of a protracted critical
      period, and propose how developmental changes in the MD contribute to successful
      prefrontal cortical development and function. Specifically, we elaborate on the
      unique properties of MD-PFC connections compared with other thalamocortical
      afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic
      transmission in the local prefrontal circuitry, and speculate on what occurs
      during postnatal development, particularly within the early neonatal stage, as
      well as juvenile and adolescent periods. Finally, we discuss the questions that
      remain and propose future experiments in order to provide perspective and novel
      insights into the cause of neuropsychiatric disorders associated with MD-PFC
      development. 

PMID- 25620926
TI  - Brain imaging, forward inference, and theories of reasoning.
AB  - This review focuses on the issue of how neuroimaging studies address theoretical
      accounts of reasoning, through the lens of the method of forward inference
      (Henson, 2005, 2006). After theories of deductive and inductive reasoning are
      briefly presented, the method of forward inference for distinguishing between
      psychological theories based on brain imaging evidence is critically reviewed.
      Brain imaging studies of reasoning, comparing deductive and inductive arguments,
      comparing meaningful versus non-meaningful material, investigating hemispheric
      localization, and comparing conditional and relational arguments, are assessed in
      light of the method of forward inference. Finally, conclusions are drawn with
      regard to future research opportunities. 

PMID- 25620927
TI  - An alternating renewal process describes the buildup of perceptual segregation.
AB  - For some ambiguous scenes perceptual conflict arises between integration and
      segregation. Initially, all stimulus features seem integrated. Then abruptly,
      perhaps after a few seconds, a segregated percept emerges. For example,
      segregation of acoustic features into streams may require several seconds. In
      behavioral experiments, when a subject's reports of stream segregation are
      averaged over repeated trials, one obtains a buildup function, a smooth time
      course for segregation probability. The buildup function has been said to reflect
      an underlying mechanism of evidence accumulation or adaptation. During long
      duration stimuli perception may alternate between integration and segregation. We
      present a statistical model based on an alternating renewal process (ARP) that
      generates buildup functions without an accumulative process. In our model,
      perception alternates during a trial between different groupings, as in
      perceptual bistability, with random and independent dominance durations sampled
      from different percept-specific probability distributions. Using this theory, we
      describe the short-term dynamics of buildup observed on short trials in terms of
      the long-term statistics of percept durations for the two alternating perceptual
      organizations. Our statistical-dynamics model describes well the buildup
      functions and alternations in simulations of pseudo-mechanistic neuronal network
      models with percept-selective populations competing through mutual inhibition.
      Even though the competition model can show history dependence through slow
      adaptation, our statistical switching model, that neglects history, predicts well
      the buildup function. We propose that accumulation is not a necessary feature to
      produce buildup. Generally, if alternations between two states exhibit
      independent durations with stationary statistics then the associated buildup
      function can be described by the statistical dynamics of an ARP. 

PMID- 25620928
TI  - Physiological modules for generating discrete and rhythmic movements: component
      analysis of EMG signals.
AB  - A central question in Neuroscience is that of how the nervous system generates
      the spatiotemporal commands needed to realize complex gestures, such as
      handwriting. A key postulate is that the central nervous system (CNS) builds up
      complex movements from a set of simpler motor primitives or control modules. In
      this study we examined the control modules underlying the generation of muscle
      activations when performing different types of movement: discrete, point-to-point
      movements in eight different directions and continuous figure-eight movements in
      both the normal, upright orientation and rotated 90 degrees . To test for the
      effects of biomechanical constraints, movements were performed in the frontal
      parallel or sagittal planes, corresponding to two different nominal
      flexion/abduction postures of the shoulder. In all cases we measured limb
      kinematics and surface electromyographic activity (EMG) signals for seven
      different muscles acting around the shoulder. We first performed principal
      component analysis (PCA) of the EMG signals on a movement-by-movement basis. We
      found a surprisingly consistent pattern of muscle groupings across movement types
      and movement planes, although we could detect systematic differences between the
      PCs derived from movements performed in each shoulder posture and between the
      principal components associated with the different orientations of the figure.
      Unexpectedly we found no systematic differences between the figure eights and the
      point-to-point movements. The first three principal components could be
      associated with a general co-contraction of all seven muscles plus two patterns
      of reciprocal activation. From these results, we surmise that both "discrete
      rhythmic movements" such as the figure eight, and discrete point-to-point
      movement may be constructed from three different fundamental modules, one
      regulating the impedance of the limb over the time span of the movement and two
      others operating to generate movement, one aligned with the vertical and the
      other aligned with the horizontal. 

PMID- 25620930
TI  - Consolidation in older adults depends upon competition between resting-state
      networks.
AB  - Memory encoding and retrieval problems are inherent to aging. To date, however,
      the effect of aging upon the neural correlates of forming memory traces remains
      poorly understood. Resting-state fMRI connectivity can be used to investigate
      initial consolidation. We compared within and between network connectivity
      differences between healthy young and older participants before encoding, after
      encoding and before retrieval by means of resting-state fMRI. Alterations over
      time in the between-network connectivity analyses correlated with retrieval
      performance, whereas within-network connectivity did not: a higher level of
      negative coupling or competition between the default mode and the executive
      networks during the after encoding condition was associated with increased
      retrieval performance in the older adults, but not in the young group. Data
      suggest that the effective formation of memory traces depends on an age
      dependent, dynamic reorganization of the interaction between multiple, large
      scale functional networks. Our findings demonstrate that a cross-network based
      approach can further the understanding of the neural underpinnings of aging
      associated memory decline. 

PMID- 25620931
TI  - Unraveling bisphenol A pharmacokinetics using physiologically based
      pharmacokinetic modeling.
AB  - Physiologically based pharmacokinetic (PBPK) models integrate both chemical- and
      system-specific information into a mathematical framework, offering a mechanistic
      approach to predict the internal dose metrics of a chemical and an ability to
      perform species and dose extrapolations. Bisphenol A (BPA), because of its
      ubiquitous presence in a variety of consumer products, has received a
      considerable amount of attention from the public and regulatory bodies. PBPK
      models using deuterated BPA were developed for immature and adult rats and non
      human primates and for adult humans to understand better the dosimetry of BPA.
      The focus of the present paper is to provide a rationale for interpreting species
      and age-related pharmacokinetics of BPA. Gastrointestinal tract metabolism was
      an important consideration to predict unconjugated BPA serum kinetic profiles in
      adult and immature rats and monkeys. Biliary excretion and enterohepatic
      recirculation of BPA conjugates (BPA-c) accounted for the slowed systemic
      clearance of BPA-c in rats. For monkeys, renal reabsorption was proposed as a
      mechanism influencing systemic clearance of BPA-c. The quantitative understanding
      of the processes driving the pharmacokinetics of BPA across different species and
      life stages using a computational modeling approach provides more confidence in
      the interpretation of human biomonitoring data and the extrapolation of
      experimental animal findings to humans. 

PMID- 25620929
TI  - Beneficial effects of nicotine, cotinine and its metabolites as potential agents
      for Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder, which is
      characterized by neuroinflammation, dopaminergic neuronal cell death and motor
      dysfunction, and for which there are no proven effective treatments. The negative
      correlation between tobacco consumption and PD suggests that tobacco-derived
      compounds can be beneficial against PD. Nicotine, the more studied alkaloid
      derived from tobacco, is considered to be responsible for the beneficial
      behavioral and neurological effects of tobacco use in PD. However, several
      metabolites of nicotine, such as cotinine, also increase in the brain after
      nicotine administration. The effect of nicotine and some of its derivatives on
      dopaminergic neurons viability, neuroinflammation, and motor and memory
      functions, have been investigated using cellular and rodent models of PD. Current
      evidence shows that nicotine, and some of its derivatives diminish oxidative
      stress and neuroinflammation in the brain and improve synaptic plasticity and
      neuronal survival of dopaminergic neurons. In vivo these effects resulted in
      improvements in mood, motor skills and memory in subjects suffering from PD
      pathology. In this review, we discuss the potential benefits of nicotine and its
      derivatives for treating PD. 

PMID- 25620932
TI  - Evaluation of mouse urinary bladder smooth muscle for diurnal differences in
      contractile properties.
AB  - Most physiological systems show daily variations in functional output, entrained
      to the day-night cycle. Humans exhibit a daily rhythm in urinary voiding
      (micturition), and disruption of this rhythm (nocturia) has significant clinical
      impact. However, the underlying mechanisms are not well-understood. Recently, a
      circadian rhythm in micturition was demonstrated in rodents, correlated with
      functional changes in urodynamics, providing the opportunity to address this
      issue in an animal model. Smooth muscle cells from mouse bladder have been
      proposed to express a functional and autonomous circadian clock at the molecular
      level. In this study, we addressed whether a semi-intact preparation of mouse
      urinary bladder smooth muscle (UBSM) exhibited measurable differences in
      contractility between day and night. UBSM tissue strips were harvested at four
      time points over the diurnal cycle, and spontaneous (phasic) and nerve-evoked
      contractions were assessed using isometric tension recordings. During the active
      period (ZT12-24) when micturition frequency is higher in rodents, UBSM strips had
      no significant differences in maximal- (high K(+)) or nerve-evoked contractions
      compared to strips harvested from the resting period (ZT0-12). However, a diurnal
      rhythm in phasic contraction was observed, with higher amplitudes at ZT10.
      Consistent with the enhanced phasic amplitudes, expression of the BK K(+)
      channel, a key suppressor of UBSM excitability, was lower at ZT8. Higher
      expression of BK at ZT20 was correlated with an enhanced effect of the BK
      antagonist paxilline (PAX) on phasic amplitude, but PAX had no significant time
      of-day dependent effect on phasic frequency or nerve-evoked contractions.
      Overall, these results identify a diurnal difference for one contractile
      parameter of bladder muscle. Taken together, the results suggest that autonomous
      clocks in UBSM make only a limited contribution to the integrated control of
      diurnal micturition patterns. 

PMID- 25620933
TI  - Forced sustained swimming exercise at optimal speed enhances growth of juvenile
      yellowtail kingfish (Seriola lalandi).
AB  - Swimming exercise at optimal speed may optimize growth performance of yellowtail
      kingfish in a recirculating aquaculture system. Therefore, optimal swimming
      speeds (U opt in m s(-1) or body lengths s(-1), BL s(-1)) were assessed and then
      applied to determine the effects of long-term forced and sustained swimming at U
      opt on growth performance of juvenile yellowtail kingfish. U opt was quantified
      in Blazka-type swim-tunnels for 145, 206, and 311 mm juveniles resulting in
      values of: (1) 0.70 m s(-1) or 4.83 BL s(-1), (2) 0.82 m s(-1) or 3.25 BL s(-1),
      and (3) 0.85 m s(-1) or 2.73 BL s(-1). Combined with literature data from larger
      fish, a relation of U opt (BL s(-1)) = 234.07(BL)(-0.779) (R (2) = 0.9909) was
      established for this species. Yellowtail kingfish, either forced to perform
      sustained swimming exercise at an optimal speed of 2.46 BL s(-1) ("swimmers") or
      allowed to perform spontaneous activity at low water flow ("resters") in a newly
      designed 3600 L oval flume (with flow created by an impeller driven by an
      electric motor), were then compared. At the start of the experiment, ten fish
      were sampled representing the initial condition. After 18 days, swimmers (n = 23)
      showed a 92% greater increase in BL and 46% greater increase in BW as compared to
      resters (n = 23). As both groups were fed equal rations, feed conversion ratio
      (FCR) for swimmers was 1.21 vs. 1.74 for resters. Doppler ultrasound imaging
      showed a statistically significant higher blood flow (31%) in the ventral aorta
      of swimmers vs. resters (44 +/- 3 vs. 34 +/- 3 mL min(-1), respectively, under
      anesthesia). Thus, growth performance can be rapidly improved by optimal
      swimming, without larger feed investments. 

PMID- 25620934
TI  - Movement disorders and psychosis, a complex marriage.

PMID- 25620936
TI  - Assessing factorial invariance of two-way rating designs using three-way methods.
AB  - Assessing the factorial invariance of two-way rating designs such as ratings of
      concepts on several scales by different groups can be carried out with three-way
      models such as the Parafac and Tucker models. By their definitions these models
      are double-metric factorially invariant. The differences between these models lie
      in their handling of the links between the concept and scale spaces. These links
      may consist of unrestricted linking (Tucker2 model), invariant component
      covariances but variable variances per group and per component (Parafac model),
      zero covariances and variances different per group but not per component
      (Replicated Tucker3 model) and strict invariance (Component analysis on the
      average matrix). This hierarchy of invariant models, and the procedures by which
      to evaluate the models against each other, is illustrated in some detail with an
      international data set from attachment theory. 

PMID- 25620935
TI  - Music induces universal emotion-related psychophysiological responses: comparing
      Canadian listeners to Congolese Pygmies.
AB  - Subjective and psychophysiological emotional responses to music from two
      different cultures were compared within these two cultures. Two identical
      experiments were conducted: the first in the Congolese rainforest with an
      isolated population of Mebenzele Pygmies without any exposure to Western music
      and culture, the second with a group of Western music listeners, with no
      experience with Congolese music. Forty Pygmies and 40 Canadians listened in pairs
      to 19 music excerpts of 29-99 s in duration in random order (eight from the Pygmy
      population and 11 Western instrumental excerpts). For both groups, emotion
      components were continuously measured: subjective feeling (using a two-
      dimensional valence and arousal rating interface), peripheral physiological
      activation, and facial expression. While Pygmy music was rated as positive and
      arousing by Pygmies, ratings of Western music by Westerners covered the range
      from arousing to calming and from positive to negative. Comparing
      psychophysiological responses to emotional qualities of Pygmy music across
      participant groups showed no similarities. However, Western stimuli, rated as
      high and low arousing by Canadians, created similar responses in both participant
      groups (with high arousal associated with increases in subjective and
      physiological activation). Several low-level acoustical features of the music
      presented (tempo, pitch, and timbre) were shown to affect subjective and
      physiological arousal similarly in both cultures. Results suggest that while the
      subjective dimension of emotional valence might be mediated by cultural learning,
      changes in arousal might involve a more basic, universal response to low-level
      acoustical characteristics of music. 

PMID- 25620937
TI  - How contrast situations affect the assignment of causality in symmetric physical
      settings.
AB  - In determining the prime cause of a physical event, people often weight one of
      two entities in a symmetric physical relation as more important for bringing
      about the causal effect than the other. In a broad survey (Bender and Beller,
      2011), we documented such weighting effects for different kinds of physical
      events and found that their direction and strength depended on a variety of
      factors. Here, we focus on one of those: adding a contrast situation that-while
      being formally irrelevant-foregrounds one of the factors and thus frames the task
      in a specific way. In two experiments, we generalize and validate our previous
      findings by using different stimulus material (in Experiment 1), by applying a
      different response format to elicit causal assignments, an analog rating scale
      instead of a forced-choice decision (in Experiment 2), and by eliciting
      explanations for the physical events in question (in both Experiments). The
      results generally confirm the contrast effects for both response formats;
      however, the effects were more pronounced with the force-choice format than with
      the rating format. People tended to refer to the given contrast in their
      explanations, which validates our manipulation. Finally, people's causal
      assignments are reflected in the type of explanation given in that contrast and
      property explanations were associated with biased causal assignments, whereas
      relational explanations were associated with unbiased assignments. In the
      discussion, we pick up the normative questions of whether or not these contrast
      effects constitute a bias in causal reasoning. 

PMID- 25620938
TI  - As naturalistic as it gets: subtitles in the English classroom in Norway.
AB  - This study aimed to investigate the effects of subtitles in the context of
      authentic material on second language comprehension and potentially, second
      language acquisition for Norwegian learners of English. Participants in the study
      were 49 17-year-old students and 65 16-year-old students, who were all native
      speakers of Norwegian learning English as an L2 in high school. Both age groups
      were divided into three Conditions, where one group watched an episode of the
      American animated cartoon Family Guy with Norwegian subtitles, one group with
      English subtitles, and one group watched the episode with no subtitles. On a
      comprehension questionnaire conducted immediately after watching the episode
      positive short-term effects of both native language (L1) and target language (L2)
      subtitles were found for both age groups. However, no differences in terms of the
      language of the subtitles were found in the older and more advanced group. Four
      weeks later the participants responded to a word definition task and a word
      recall task to investigate potential long-term effects of the subtitles. The only
      long-term effect was found in the word definition task and was modulated by age.
      We found, however, that native language subtitles impact negatively on
      performance on the comprehension task. The results from this study suggest that
      the mere presence of subtitles as an additional source of information enhances
      learners' comprehension of the plot and content in animated audio-visual material
      in their L2. The absence of differences in terms of the language of the subtitles
      in the more advanced group suggests that both intralanguage and interlanguage
      subtitles can aid target language comprehension in very advanced learners, most
      probably due to better consolidated vocabulary knowledge in that group. The two
      groups differed also on predictors of performance on the two lexical tasks. While
      in the less proficient younger group, vocabulary status best predicted
      performance on both tasks (vocabulary predicts vocabulary), for the very advanced
      older group, grammar was a stronger predictor, highlighting the importance of
      generic language competence and skills in L2 tasks for highly proficient L2
      users. We also found an effect of written L2 skills on performance on both
      lexical tasks indicative of the role of orthography in vocabulary consolidation. 

PMID- 25620940
TI  - Cognitive penetration and the gallery of indiscernibles.

PMID- 25620939
TI  - Independent development of the Reach and the Grasp in spontaneous self-touching
      by human infants in the first 6 months.
AB  - The Dual Visuomotor Channel Theory proposes that visually guided reaching is a
      composite of two movements, a Reach that advances the hand to contact the target
      and a Grasp that shapes the digits for target purchase. The theory is supported
      by biometric analyses of adult reaching, evolutionary contrasts, and differential
      developmental patterns for the Reach and the Grasp in visually guided reaching in
      human infants. The present ethological study asked whether there is evidence for
      a dissociated development for the Reach and the Grasp in nonvisual hand use in
      very early infancy. The study documents a rich array of spontaneous self-touching
      behavior in infants during the first 6 months of life and subjected the Reach
      movements to an analysis in relation to body target, contact type, and Grasp.
      Video recordings were made of resting alert infants biweekly from birth to 6
      months. In younger infants, self-touching targets included the head and trunk. As
      infants aged, targets became more caudal and included the hips, then legs, and
      eventually the feet. In younger infants hand contact was mainly made with the
      dorsum of the hand, but as infants aged, contacts included palmar contacts and
      eventually grasp and manipulation contacts with the body and clothes. The
      relative incidence of caudal contacts and palmar contacts increased concurrently
      and were significantly correlated throughout the period of study. Developmental
      increases in self-grasping contacts occurred a few weeks after the increase in
      caudal and palmar contacts. The behavioral and temporal pattern of these
      spontaneous self-touching movements suggest that the Reach, in which the hand
      extends to make a palmar self-contact, and the Grasp, in which the digits close
      and make manipulatory movements, have partially independent developmental
      profiles. The results additionally suggest that self-touching behavior is an
      important developmental phase that allows the coordination of the Reach and the
      Grasp prior to and concurrent with their use under visual guidance. 

PMID- 25620941
TI  - Logical-rules and the classification of integral dimensions: individual
      differences in the processing of arbitrary dimensions.
AB  - A variety of converging operations demonstrate key differences between separable
      dimensions, which can be analyzed independently, and integral dimensions, which
      are processed in a non-analytic fashion. A recent investigation of response time
      distributions, applying a set of logical rule-based models, demonstrated that
      integral dimensions are pooled into a single coactive processing channel, in
      contrast to separable dimensions, which are processed in multiple, independent
      processing channels. This paper examines the claim that arbitrary dimensions
      created by factorially morphing four faces are processed in an integral manner.
      In two experiments, 16 participants completed a categorization task in which
      either upright or inverted morph stimuli were classified in a speeded fashion.
      Analyses focused on contrasting different assumptions about the psychological
      representation of the stimuli, perceptual and decisional separability, and the
      processing architecture. We report consistent individual differences which
      demonstrate a mixture of some observers who demonstrate coactive processing with
      other observers who process the dimensions in a parallel self-terminating manner.

PMID- 25620942
TI  - Weighty data: importance information influences estimated weight of digital
      information storage devices.
AB  - Previous work suggests that perceived importance of an object influences
      estimates of its weight. Specifically, important books were estimated to be
      heavier than non-important books. However, the experimental set-up of these
      studies may have suffered from a potential confound and findings may be confined
      to books only. Addressing this, we investigate the effect of importance on weight
      estimates by examining whether the importance of information stored on a data
      storage device (USB-stick or portable hard drive) can alter weight estimates.
      Results show that people thinking a USB-stick holds important tax information
      (vs. expired tax information vs. no information) estimate it to be heavier
      (Experiment 1) compared to people who do not. Similarly, people who are told a
      portable hard drive holds personally relevant information (vs. irrelevant), also
      estimate the drive to be heavier (Experiments 2A,B). 

PMID- 25620943
TI  - Visual statistical learning in children and young adults: how implicit?
AB  - Visual statistical learning (VSL) is the ability to extract the joint and
      conditional probabilities of shapes co-occurring during passive viewing of
      complex visual configurations. Evidence indicates that even infants are sensitive
      to these regularities (e.g., Kirkham et al., 2002). However, there is continuing
      debate as to whether VSL is accompanied by conscious awareness of the statistical
      regularities between sequence elements. Bertels et al. (2012) addressed this
      question in young adults. Here, we adapted their paradigm to investigate VSL and
      conscious awareness in children. Using the same version of the paradigm, we also
      tested young adults so as to directly compare results from both age groups. Fifth
      graders and undergraduates were exposed to a stream of visual shapes arranged in
      triplets. Learning of these sequences was then assessed using both direct and
      indirect measures. In order to assess the extent to which learning occurred
      explicitly, we also measured confidence through subjective measures in the direct
      task (i.e., binary confidence judgments). Results revealed that both children and
      young adults learned the statistical regularities between shapes. In both age
      groups, participants who performed above chance in the completion task had
      conscious access to their knowledge. Nevertheless, although adults performed
      above chance even when they claimed to guess, there was no evidence of implicit
      knowledge in children. These results suggest that the role of implicit and
      explicit influences in VSL may follow a developmental trajectory. 

PMID- 25620944
TI  - Multimodal theories of recognition and their relation to Molyneux's question.

PMID- 25620946
TI  - Syntactic theory is also a metaphor.

PMID- 25620947
TI  - The social-devaluation effect: interactive evaluation deteriorates likeability of
      objects based on daily relationship.
AB  - Although previous research has explored the effects of discussion on optimal and
      collective group outcomes, it is unclear how an individual's preference for an
      object is modulated by discussion with others. This study investigated the
      determinants of likeability ratings under two conditions. In Experiment 1, pairs
      of participants consisting of friends evaluated various photographic images.
      Under the interactive condition, the participants discussed their impressions of
      each image for 30 s and then independently rated how much they liked it. Under
      the non-interactive condition, the participants did not interact with each other
      but instead only thought about their impressions of each image for 30 s before
      rating its likeability. The results indicate that the exchange of impressions
      between the participants affected the individual likeability ratings of objects.
      More specifically, the interactive participants generally rated the images as
      less likeable than did the non-interactive participants (social-devaluation
      effect). However, in Experiment 2, the effect was eliminated when the pairs
      consisted of strangers. These findings suggest that shared information modulates
      individual preferences but only when a daily relationship exists within a group. 

PMID- 25620945
TI  - What are memory-perception interactions for? Implications for action.

PMID- 25620948
TI  - Why live recording sounds better: a case study of Schumann's Traumerei.
AB  - We explore the concept that artists perform best in front of an audience. The
      negative effects of performance anxiety are much better known than their related
      cousin on the other shoulder: the positive effects of "social facilitation." The
      present study, however, reveals a listener's preference for performances recorded
      in front of an audience. In Study 1, we prepared two types of recordings of
      Traumerei performed by 13 pianists: recordings in front of an audience and those
      with no audience. According to the evaluation by 153 listeners, the recordings
      performed in front of an audience sounded better, suggesting that the presence of
      an audience enhanced or facilitated the performance. In Study 2, we analyzed
      pianists' durational and dynamic expressions. According to the functional
      principal components analyses, we found that the expression of "Traumerei"
      consisted of three components: the overall quantity, the cross-sectional contrast
      between the final and the remaining sections, and the control of the expressive
      variability. Pianists' expressions were targeted more to the "average" of the
      cross-sectional variation in the audience-present than in the audience-absent
      recordings. In Study 3, we explored a model that explained listeners' responses
      induced by pianists' acoustical expressions, using path analyses. The final model
      indicated that the cross-sectional variation of the duration and that of the
      dynamics determined listeners' evaluations of the quality and the emotionally
      moving experience, respectively. In line with human's preferences for
      commonality, the more "average" the durational expressions were in live
      recording, the better the listeners' evaluations were regardless of their musical
      experiences. Only the well-experienced listeners (at least 16 years of musical
      training) were moved more by the "deviated" dynamic expressions in live
      recording, suggesting a link between the experienced listener's emotional
      experience and the unique dynamics in music. 

PMID- 25620949
TI  - The relevance of the cross-wavelet transform in the analysis of human interaction
      - a tutorial.
AB  - This article sheds light on a quantitative method allowing psychologists and
      behavioral scientists to take into account the specific characteristics emerging
      from the interaction between two sets of data in general and two individuals in
      particular. The current article outlines the practical elements of the cross
      wavelet transform (CWT) method, highlighting WHY such a method is important in
      the analysis of time-series in psychology. The idea is (1) to bridge the gap
      between physical measurements classically used in physiology - neuroscience and
      psychology; (2) and demonstrates how the CWT method can be applied in psychology.
      One of the aims is to answer three important questions WHO could use this method
      in psychology, WHEN it is appropriate to use it (suitable type of time-series)
      and HOW to use it. Throughout these explanations, an example with simulated data
      is used. Finally, data from real life application are analyzed. This data
      corresponds to a rating task where the participants had to rate in real time the
      emotional expression of a person. The objectives of this practical example are
      (i) to point out how to manipulate the properties of the CWT method on real data,
      (ii) to show how to extract meaningful information from the results, and (iii) to
      provide a new way to analyze psychological attributes. 

PMID- 25620950
TI  - The comfort of approach: self-soothing effects of behavioral approach in response
      to meaning violations.
AB  - People maintain systems of beliefs that provide them with a sense of
      belongingness, control, identity, and meaning, more generally. Recent research
      shows that when these beliefs are threatened a syndrome of negatively valenced
      arousal is evoked that motivates people to seek comfort in their ideologies or
      other personally valued beliefs. In this paper we will provide an overview of
      this process and discuss areas for future research. Beginning with the neural
      foundations of meaning violations, we review findings that show the anterior
      cingulate cortex is responsible for detecting inconsistencies, and importantly,
      that this is experienced as aversive. Next, we evaluate the evidential support
      for a psychophysiological arousal response as measured by cardiography and skin
      conductance. We discuss how current theorizing proposes that subsequent
      behavioral approach ameliorates the negative arousal and serves as an effective,
      well-adapted coping response, but we also aim to further integrate this process
      in the existing threat-compensation literature. Finally, we speculate on whether
      approach motivation is likely to result when one feels capable of handling the
      threat, thereby incorporating the biopsychosocial model that distinguishes
      between challenge and threat into the motivational threat-response literature. We
      believe the current literature on threat and meaning has much to offer and we aim
      to provide new incentives for further development. 

PMID- 25620951
TI  - The need to control for regression to the mean in social psychology studies.
AB  - It is common in repeated measurements for extreme values at the first measurement
      to approach the mean at the subsequent measurement, a phenomenon called
      regression to the mean (RTM). If RTM is not fully controlled, it will lead to
      erroneous conclusions. The wide use of repeated measurements in social psychology
      creates a risk that an RTM effect will influence results. However, insufficient
      attention is paid to RTM in most social psychological research. Notable cases
      include studies on the phenomena of social conformity and unrealistic optimism
      (Klucharev et al., 2009, 2011; Sharot et al., 2011, 2012b; Campbell-Meiklejohn et
      al., 2012; Kim et al., 2012; Garrett and Sharot, 2014). In Study 1, 13 university
      students rated and re-rated the facial attractiveness of a series of female faces
      as a test of the social conformity effect (Klucharev et al., 2009). In Study 2,
      15 university students estimated and re-estimated their risk of experiencing a
      series of adverse life events as a test of the unrealistic optimism effect
      (Sharot et al., 2011). Although these studies used methodologies similar to those
      used in earlier research, the social conformity and unrealistic optimism effects
      were no longer evident after controlling for RTM. Based on these findings we
      suggest several ways to control for the RTM effect in social psychology studies,
      such as adding the initial rating as a covariate in regression analysis,
      selecting a subset of stimuli for which the participant' initial ratings were
      matched across experimental conditions, and using a control group. 

PMID- 25620953
TI  - Diffuse decreased gray matter in patients with idiopathic craniocervical
      dystonia: a voxel-based morphometry study.
AB  - BACKGROUND: Recent studies have addressed the role of structures other than the
      basal ganglia in the pathophysiology of craniocervical dystonia (CCD).
      Neuroimaging studies have attempted to identify structural abnormalities in CCD
      but a clear pattern of alteration has not been established. We performed whole
      brain evaluation using voxel-based morphometry (VBM) to identify patterns of gray
      matter (GM) changes in CCD. METHODS: We compared 27 patients with CCD matched in
      age and gender to 54 healthy controls. VBM was used to compare GM volumes. We
      created a two-sample t-test corrected for subjects' age, and we tested with a
      level of significance of p < 0.001 and false discovery rate (FDR) correction (p <
      0.05). RESULTS: Voxel-based morphometry demonstrated significant reductions of GM
      using p < 0.001 in the cerebellar vermis IV/V, bilaterally in the superior
      frontal gyrus, precuneus, anterior cingulate and paracingulate, insular cortex,
      lingual gyrus, and calcarine fissure; in the left hemisphere in the supplementary
      motor area, inferior frontal gyrus, inferior parietal gyrus, temporal pole,
      supramarginal gyrus, rolandic operculum, hippocampus, middle occipital gyrus,
      cerebellar lobules IV/V, superior, and middle temporal gyri; in the right
      hemisphere, the middle cingulate and precentral gyrus. Our study did not report
      any significant result using the FDR correction. We also detected correlations
      between GM volume and age, disease duration, duration of botulinum toxin
      treatment, and the Marsden-Fahn dystonia scale scores. CONCLUSION: We detected
      large clusters of GM changes chiefly in structures primarily involved in
      sensorimotor integration, motor planning, visuospatial function, and emotional
      processing.

PMID- 25620952
TI  - Efficacy and Safety of Panax notoginseng Saponin Therapy for Acute Intracerebral
      Hemorrhage, Meta-Analysis, and Mini Review of Potential Mechanisms of Action.
AB  - Intracranial/intracerebral hemorrhage (ICH) is a leading cause of death and
      disability in people with traumatic brain injury (TBI) and stroke. No proven drug
      is available for ICH. Panax notoginseng (total saponin extraction, PNS) is one of
      the most valuable herb medicines for stroke and cerebralvascular disorders in
      China. We searched for randomized controlled clinical trials (RCTs) involving PNS
      injection to treat cerebral hemorrhage for meta-analysis from various databases
      including the Chinese Stroke Trials Register, the trials register of the Cochrane
      Complementary Medicine Field, the Cochrane Central Register of Controlled Trials,
      MEDLINE, Chinese BioMedical disk, and China Doctorate/Master Dissertations
      Databases. The quality of the eligible trials was assessed by Jadad's scale.
      Twenty (20) of the 24 identified randomized controlled trials matched the
      inclusive criteria including 984 ICH patients with PNS injection and 907 ICH
      patients with current treatment (CT). Compared to the CT groups, PNS-treated
      patients showed better outcomes in the effectiveness rate (ER), neurological
      deficit score, intracranial hematoma volume, intracerebral edema volume, Barthel
      index, the number of patients died, and incidence of adverse events. CONCLUSION:
      PNS injection is superior to CT for acute ICH. A review of the literature shows
      that PNS may exert multiple protective mechanisms against ICH-induced brain
      damage including hemostasis, anti-coagulation, anti-thromboembolism, cerebral
      vasodilation, invigorated blood dynamics, anti-inflammation, antioxidation, and
      anti-hyperglycemic effects. Since vitamin C and other brain cell activators (BCA)
      that are not considered common practice were also used as parts of the CT in
      several trials, potential PNS and BCA interactions could exist that may have made
      the effect of PNS therapy less or more impressive than by PNS therapy alone.
      Future PNS trials with and without the inclusion of such controversial BCAs as
      part of the CT could clarify the situation. As PNS has a long clinical track
      record in Asia, it could potentially become a therapy option to treat ICH in the
      US and Europe. Further clinical trials with better experimental design could
      determine the long-term effects of PNS treatment for TBI and stroke.

PMID- 25620954
TI  - Movement recognition technology as a method of assessing spontaneous general
      movements in high risk infants.
AB  - Preterm birth is associated with increased risks of neurological and motor
      impairments such as cerebral palsy. The risks are highest in those born at the
      lowest gestations. Early identification of those most at risk is challenging
      meaning that a critical window of opportunity to improve outcomes through therapy
      based interventions may be missed. Clinically, the assessment of spontaneous
      general movements is an important tool, which can be used for the prediction of
      movement impairments in high risk infants. Movement recognition aims to capture
      and analyze relevant limb movements through computerized approaches focusing on
      continuous, objective, and quantitative assessment. Different methods of
      recording and analyzing infant movements have recently been explored in high risk
      infants. These range from camera-based solutions to body-worn miniaturized
      movement sensors used to record continuous time-series data that represent the
      dynamics of limb movements. Various machine learning methods have been developed
      and applied to the analysis of the recorded movement data. This analysis has
      focused on the detection and classification of atypical spontaneous general
      movements. This article aims to identify recent translational studies using
      movement recognition technology as a method of assessing movement in high risk
      infants. The application of this technology within pediatric practice represents
      a growing area of inter-disciplinary collaboration, which may lead to a greater
      understanding of the development of the nervous system in infants at high risk of
      motor impairment. 

PMID- 25620955
TI  - Sex differences in behavioral circadian rhythms in laboratory rodents.
AB  - There is a strong bias in basic research on circadian rhythms toward the use of
      only male animals in studies. Furthermore, of the studies that use female
      subjects, many use only females and do not compare results between males and
      females. This review focuses on behavioral aspects of circadian rhythms that
      differ between the sexes. Differences exist in the timing of daily onset of
      activity, responses to both photic and non-photic stimuli, and in changes across
      the lifespan. These differences may reflect biologically important traits that
      are ecologically relevant and impact on a variety of responses to behavioral and
      physiological challenges. Overall, more work needs to be done to investigate
      differences between males and females as well as differences that are the result
      of hormonal changes across the lifespan. 

PMID- 25620956
TI  - O-GlcNAcylation and Inflammation: A Vast Territory to Explore.
AB  - O-GlcNAcylation is a reversible post-translational modification that regulates
      the activities of cytosolic and nuclear proteins according to glucose
      availability. This modification appears to participate in several hyperglycemia
      associated complications. An important feature of metabolic diseases such as
      diabetes and obesity is the presence of a low-grade chronic inflammation that
      causes numerous complications. Hyperglycemia associated with the metabolic
      syndrome is known to promote inflammatory processes through different mechanisms
      including oxidative stress and abnormally elevated protein O-GlcNAcylation.
      However, the role of O-GlcNAcylation on inflammation remains contradictory. O
      GlcNAcylation associated with hyperglycemia has been shown to increase nuclear
      factor kappaB (NFkappaB) transcriptional activity through different mechanisms.
      This could contribute in inflammation-associated diabetic complications. However,
      in other conditions such as acute vascular injury, O-linked N-acetyl glucosamine
      (O-GlcNAc) also exerts anti-inflammatory effects via inhibition of the NFkappaB
      pathway, suggesting a complex regulation of inflammation by O-GlcNAc. Moreover,
      whereas macrophages and monocytes exposed to high glucose for a long-term period
      developed a pro-inflammatory phenotype, the impact of O-GlcNAcylation in these
      cells remains unclear. A future challenge will be to clearly establish the role
      of O-GlcNAcylation in pro- and anti-inflammatory functions in macrophages. 

PMID- 25620957
TI  - Endophytic fungi: a reservoir of antibacterials.
AB  - Multidrug drug resistant bacteria are becoming increasingly problematic
      particularly in the under developed countries of the world. The most important
      microorganisms that have seen a geometric rise in numbers are Methicillin
      resistant Staphylococcus aureus, Vancomycin resistant Enterococcus faecium,
      Penicillin resistant Streptococcus pneumonia and multiple drug resistant
      tubercule bacteria to name a just few. New drug scaffolds are essential to tackle
      this every increasing problem. These scaffolds can be sourced from nature itself.
      Endophytic fungi are an important reservoir of therapeutically active compounds.
      This review attempts to present some data relevant to the problem. New, very
      specific and effective antibiotics are needed but also at an affordable price! A
      Herculean task for researchers all over the world! In the Asian subcontinent
      indigenous therapeutics that has been practiced over the centuries such as
      Ayurveda have been effective as "handed down data" in family generations. May
      need a second, third and more "in-depth investigations?" 

PMID- 25620958
TI  - Benthic ammonia oxidizers differ in community structure and biogeochemical
      potential across a riverine delta.
AB  - Nitrogen pollution in coastal zones is a widespread issue, particularly in
      ecosystems with urban or agricultural watersheds. California's Sacramento-San
      Joaquin Delta, at the landward reaches of San Francisco Bay, is highly impacted
      by both agricultural runoff and sewage effluent, leading to chronically high
      nutrient loadings. In particular, the extensive discharge of ammonium into the
      Sacramento River has altered this ecosystem by vastly increasing ammonium
      concentrations and thus changing the stoichiometry of inorganic nitrogen stocks,
      with potential effects throughout the food web. This debate surrounding ammonium
      inputs highlights the importance of understanding the rates of, and controls on,
      nitrogen (N) cycling processes across the delta. To date, however, there has been
      little research examining N biogeochemistry or N-cycling microbial communities in
      this system. We report the first data on benthic ammonia-oxidizing microbial
      communities and potential nitrification rates for the Sacramento-San Joaquin
      Delta, focusing on the functional gene amoA (which codes for the alpha-subunit of
      ammonia monooxygenase). There were stark regional differences in ammonia
      oxidizing communities, with ammonia-oxidizing bacteria (AOB) outnumbering ammonia
      oxidizing archaea (AOA) only in the ammonium-rich Sacramento River. High
      potential nitrification rates in the Sacramento River suggested these communities
      may be capable of oxidizing significant amounts of ammonium, compared to the San
      Joaquin River and the upper reaches of San Francisco Bay. Gene diversity also
      showed regional patterns, as well as phylogenetically unique ammonia oxidizers in
      the Sacramento River. The benthic ammonia oxidizers in this nutrient-rich aquatic
      ecosystem may be important players in its overall nutrient cycling, and their
      community structure and biogeochemical function appear related to nutrient
      loadings. Unraveling the microbial ecology and biogeochemistry of N cycling
      pathways, including benthic nitrification, is a critical step toward
      understanding how such ecosystems respond to the changing environmental
      conditions wrought by human development and climate change. 

PMID- 25620959
TI  - Transduction of the Streptococcus pyogenes bacteriophage Phim46.1, carrying
      resistance genes mef(A) and tet(O), to other Streptococcus species.
AB  - Phim46.1 - Streptococcus pyogenes bacteriophage carrying mef(A) and tet(O),
      respectively, encoding resistance to macrolides (M phenotype) and tetracycline -
      is widespread in S. pyogenes but has not been reported outside this species.
      Phim46.1 is transferable in vitro among S. pyogenes isolates, but no information
      is available about its transferability to other Streptococcus species. We thus
      investigated Phim46.1 for its ability to be transduced in vitro to recipients of
      different Streptococcus species. Transductants were obtained from recipients of
      Streptococcus agalactiae, Streptococcus gordonii, and Streptococcus suis.
      Retransfer was always achieved, and from S. suis to S. pyogenes occurred at a
      much greater frequency than in the opposite direction. In transductants Phim46.1
      retained its functional properties, such as inducibility with mitomycin C,
      presence both as a prophage and as a free circular form, and transferability. The
      transductants shared the same Phim46.1 chromosomal integration site as the donor,
      at the 3' end of a conserved RNA uracil methyltransferase (rum) gene, which is an
      integration hotspot for a variety of genetic elements. No transfer occurred to
      recipients of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus
      salivarius, even though rum-like genes were also detected in the sequenced
      genomes of these species. A largely overlapping 18-bp critical sequence, where
      the site-specific recombination process presumably takes place, was identified in
      the rum genes of all recipients, including those of the species yielding no
      transductants. Growth assays to evaluate the fitness cost of Phim46.1 acquisition
      disclosed a negligible impact on S. pyogenes, S. agalactiae, and S. gordonii
      transductants and a noticeable fitness advantage in S. suis. The S. suis
      transductant also displayed marked overexpression of the autolysin-encoding gene
      atl. 

PMID- 25620960
TI  - Seasonal dynamics of bacterial and archaeal methanogenic communities in flooded
      rice fields and effect of drainage.
AB  - We studied the resident (16S rDNA) and the active (16S rRNA) members of soil
      archaeal and bacterial communities during rice plant development by sampling
      three growth stages (vegetative, reproductive and maturity) under field
      conditions. Additionally, the microbial community was investigated in two non
      flooded fields (unplanted, cultivated with upland maize) in order to monitor the
      reaction of the microbial communities to non-flooded, dry conditions. The
      abundance of Bacteria and Archaea was monitored by quantitative PCR showing an
      increase in 16S rDNA during reproductive stage and stable 16S rRNA copies
      throughout the growth season. Community profiling by T-RFLP indicated a
      relatively stable composition during rice plant growth whereas pyrosequencing
      revealed minor changes in relative abundance of a few bacterial groups.
      Comparison of the two non-flooded fields with flooded rice fields showed that the
      community composition of the Bacteria was slightly different, while that of the
      Archaea was almost the same. Only the relative abundance of Methanosarcinaceae
      and Soil Crenarchaeotic Group increased in non-flooded vs. flooded soil. The
      abundance of bacterial and archaeal 16S rDNA copies was highest in flooded rice
      fields, followed by non-flooded maize and unplanted fields. However, the
      abundance of ribosomal RNA (active microbes) was similar indicating maintenance
      of a high level of ribosomal RNA under the non-flooded conditions, which were
      unfavorable for anaerobic bacteria and methanogenic archaea. This maintenance
      possibly serves as preparedness for activity when conditions improve. In summary,
      the analyses showed that the bacterial and archaeal communities inhabiting
      Philippine rice field soil were relatively stable over the season but reacted
      upon change in field management. 

PMID- 25620961
TI  - Antibiotic resistance genes in food and gut (non-pathogenic) bacteria. Bad genes
      in good bugs.

PMID- 25620962
TI  - Metagenomic insights into S(0) precipitation in a terrestrial subsurface
      lithoautotrophic ecosystem.
AB  - The Frasassi and Acquasanta Terme cave systems in Italy host isolated
      lithoautotrophic ecosystems characterized by sulfur-oxidizing biofilms with up to
      50% S(0) by mass. The net contributions of microbial taxa in the biofilms to
      production and consumption of S(0) are poorly understood and have implications
      for understanding the formation of geological sulfur deposits as well as the
      ecological niches of sulfur-oxidizing autotrophs. Filamentous
      Epsilonproteobacteria are among the principal biofilm architects in Frasassi and
      Acquasanta Terme streams, colonizing high-sulfide, low-oxygen niches relative to
      other major biofilm-forming populations. Metagenomic sequencing of eight biofilm
      samples indicated the presence of diverse and abundant Epsilonproteobacteria.
      Populations of Sulfurovum-like organisms were the most abundant
      Epsilonproteobacteria regardless of differences in biofilm morphology,
      temperature, or water chemistry. After assembling and binning the metagenomic
      data, we retrieved four nearly-complete genomes of Sulfurovum-like organisms as
      well as a Sulfuricurvum spp. Analyses of the binned and assembled metagenomic
      data indicate that the Epsilonproteobacteria are autotrophic and therefore
      provide organic carbon to the isolated subsurface ecosystem. Multiple homologs of
      sulfide-quinone oxidoreductase (Sqr), together with incomplete or absent Sox
      pathways, suggest that cave Sulfurovum-like Epsilonproteobacteria oxidize sulfide
      incompletely to S(0) using either O2 or nitrate as a terminal electron acceptor,
      consistent with previous evidence that they are most successful in niches with
      high dissolved sulfide to oxygen ratios. In contrast, we recovered homologs of
      the complete complement of Sox proteins affiliated Gammaproteobacteria and with
      less abundant Sulfuricurvum spp. and Arcobacter spp., suggesting that these
      populations are capable of the complete oxidation of sulfide to sulfate. These
      and other genomic data presented here offer new clues into the physiology and
      genetic potential of the largely uncultivated and ecologically successful cave
      Sulfurovum-like populations, and suggest that they play an integral role in
      subsurface S(0) formation. 

PMID- 25620963
TI  - Characterization of shed medicinal leech mucus reveals a diverse microbiota.
AB  - Microbial transmission through mucosal-mediated mechanisms is widespread
      throughout the animal kingdom. One example of this occurs with Hirudo verbana,
      the medicinal leech, where host attraction to shed conspecific mucus facilitates
      horizontal transmission of a predominant gut symbiont, the Gammaproteobacterium
      Aeromonas veronii. However, whether this mucus may harbor other bacteria has not
      been examined. Here, we characterize the microbiota of shed leech mucus through
      Illumina deep sequencing of the V3-V4 hypervariable region of the 16S rRNA gene.
      Additionally, Restriction Fragment Length Polymorphism (RFLP) typing with
      subsequent Sanger Sequencing of a 16S rRNA gene clone library provided
      qualitative confirmation of the microbial composition. Phylogenetic analyses of
      full-length 16S rRNA sequences were performed to examine microbial taxonomic
      distribution. Analyses using both technologies indicate the dominance of the
      Bacteroidetes and Proteobacteria phyla within the mucus microbiota. We determined
      the presence of other previously described leech symbionts, in addition to a
      number of putative novel leech-associated bacteria. A second predominant gut
      symbiont, the Rikenella-like bacteria, was also identified within mucus and
      exhibited similar population dynamics to A. veronii, suggesting persistence in
      syntrophy beyond the gut. Interestingly, the most abundant bacterial genus
      belonged to Pedobacter, which includes members capable of producing heparinase,
      an enzyme that degrades the anticoagulant, heparin. Additionally, bacteria
      associated with denitrification and sulfate cycling were observed, indicating an
      abundance of these anions within mucus, likely originating from the leech
      excretory system. A diverse microbiota harbored within shed mucus has significant
      potential implications for the evolution of microbiomes, including opportunities
      for gene transfer and utility in host capture of a diverse group of symbionts. 

PMID- 25620964
TI  - Predicting copper-, iron-, and zinc-binding proteins in pathogenic species of the
      Paracoccidioides genus.
AB  - Approximately one-third of all proteins have been estimated to contain at least
      one metal cofactor, and these proteins are referred to as metalloproteins. These
      represent one of the most diverse classes of proteins, containing metal ions that
      bind to specific sites to perform catalytic, regulatory and structural functions.
      Bioinformatic tools have been developed to predict metalloproteins encoded by an
      organism based only on its genome sequence. Its function and the type of metal
      binder can also be predicted via a bioinformatics approach. Paracoccidioides
      complex includes termodimorphic pathogenic fungi that are found as saprobic
      mycelia in the environment and as yeast, the parasitic form, in host tissues.
      They are the etiologic agents of Paracoccidioidomycosis, a prevalent systemic
      mycosis in Latin America. Many metalloproteins are important for the virulence of
      several pathogenic microorganisms. Accordingly, the present work aimed to predict
      the copper, iron and zinc proteins encoded by the genomes of three phylogenetic
      species of Paracoccidioides (Pb01, Pb03, and Pb18). The metalloproteins were
      identified using bioinformatics approaches based on structure, annotation and
      domains. Cu-, Fe-, and Zn-binding proteins represent 7% of the total proteins
      encoded by Paracoccidioides spp. genomes. Zinc proteins were the most abundant
      metalloproteins, representing 5.7% of the fungus proteome, whereas copper and
      iron proteins represent 0.3 and 1.2%, respectively. Functional classification
      revealed that metalloproteins are related to many cellular processes.
      Furthermore, it was observed that many of these metalloproteins serve as
      virulence factors in the biology of the fungus. Thus, it is concluded that the
      Cu, Fe, and Zn metalloproteomes of the Paracoccidioides spp. are of the utmost
      importance for the biology and virulence of these particular human pathogens. 

PMID- 25620965
TI  - Protective host defense against disseminated candidiasis is impaired in mice
      expressing human interleukin-37.
AB  - The effect of the anti-inflammatory cytokine interleukin-37 (IL-37) on host
      defense against Candida infections remains unknown. We assessed the role of IL-37
      in a murine model of disseminated candidiasis using mice transgenic for human IL
      37 (hIL-37Tg). Upon exposure to Candida albicans pseudohyphae, macrophages from
      hIL-37Tg mice release 39% less TNFalpha compared to cells from wild-type (WT)
      mice (p = 0.01). In vivo, hIL-37Tg mice displayed a decreased capacity to recruit
      neutrophils to the site of infection. These defects were associated with
      increased mortality and organ fungal growth in hIL-37Tg compared to WT mice. We
      conclude that IL-37 interferes with the innate protective anti-Candida host
      response by reducing the production of proinflammatory cytokines and suppressing
      neutrophil recruitment in response to Candida, resulting in an increased
      susceptibility to disseminated candidiasis. 

PMID- 25620966
TI  - Reconstructing each cell's genome within complex microbial communities-dream or
      reality?
AB  - As the vast majority of microorganisms have yet to be cultivated in a laboratory
      setting, access to their genetic makeup has largely been limited to cultivation
      independent methods. These methods, namely metagenomics and more recently single
      cell genomics, have become cornerstones for microbial ecology and environmental
      microbiology. One ultimate goal is the recovery of genome sequences from each
      cell within an environment to move toward a better understanding of community
      metabolic potential and to provide substrate for experimental work. As single
      cell sequencing has the ability to decipher all sequence information contained in
      an individual cell, this method holds great promise in tackling such challenge.
      Methodological limitations and inherent biases however do exist, which will be
      discussed here based on environmental and benchmark data, to assess how far we
      are from reaching this goal. 

PMID- 25620967
TI  - Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of
      the Antiviral Factor Tetherin.
AB  - Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have
      been well characterized. In these cases, lncRNAs have been shown to be key
      regulators of several cellular processes. Therefore, there is a great need to
      understand the function of more lncRNAs and their regulation in response to
      stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response.
      IFN binding to its receptor activates transcription of several IFN-stimulated
      genes (ISGs) that function as potent antivirals. In addition, several ISGs are
      positive or negative regulators of the IFN pathway. This is essential to ensure a
      strong antiviral response and a later return of the cell to homeostasis. As the
      ISGs described to date are coding genes, we sought to determine whether IFN also
      regulates the expression of long non-coding ISGs. To this aim, we used RNA
      sequencing to analyze the transcriptome of control and HuH7 cells treated with
      IFNalpha2. The results show that IFN-treatment regulates the expression of
      several unknown non-coding transcripts. We have validated two lncRNAs upregulated
      after treatment with different doses of type I IFNalpha2 in different cells or
      with type III IFNlambda. These lncRNAs were also induced by influenza and
      vesicular stomatitis virus mutants unable to block the IFN response, but not by
      several wild-type lytic viruses tested. These lncRNA genes were named lncISG15
      and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively.
      Interestingly, inhibition experiments showed that lncBST2 is a positive regulator
      of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated
      positive regulator. Our results may have therapeutic implications as
      lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in
      cells infected with hepatitis C virus and in the liver of infected patients.
      These results allow us to hypothesize that several lncRNAs could be activated by
      IFN to control the potency of the antiviral IFN response. 

PMID- 25620968
TI  - Characterization of the inositol monophosphatase gene family in Arabidopsis.
AB  - Synthesis of myo-inositol is crucial in multicellular eukaryotes for production
      of phosphatidylinositol and inositol phosphate signaling molecules. The myo
      inositol monophosphatase (IMP) enzyme is required for the synthesis of myo
      inositol, breakdown of inositol (1,4,5)-trisphosphate, a second messenger
      involved in Ca(2+) signaling, and synthesis of L-galactose, a precursor of
      ascorbic acid. Two myo-inositol monophosphatase -like (IMPL) genes in Arabidopsis
      encode chloroplast proteins with homology to the prokaryotic IMPs and one of
      these, IMPL2, can complement a bacterial histidinol 1-phosphate phosphatase
      mutant defective in histidine synthesis, indicating an important role for IMPL2
      in amino acid synthesis. To delineate how this small gene family functions in
      inositol synthesis and metabolism, we sought to compare recombinant enzyme
      activities, expression patterns, and impact of genetic loss-of-function mutations
      for each. Our data show that purified IMPL2 protein is an active histidinol
      phosphate phosphatase enzyme in contrast to the IMPL1 enzyme, which has the
      ability to hydrolyze D-galactose 1-phosphate, and D-myo-inositol 1-phosphate, a
      breakdown product of D-inositol (1,4,5) trisphosphate. Expression studies
      indicated that all three genes are expressed in multiple tissues, however, IMPL1
      expression is restricted to above-ground tissues only. Identification and
      characterization of impl1 and impl2 mutants revealed no viable mutants for IMPL1,
      while two different impl2 mutants were identified and shown to be severely
      compromised in growth, which can be rescued by histidine. Analyses of metabolite
      levels in impl2 and complemented mutants reveals impl2 mutant growth is impacted
      by alterations in the histidine biosynthesis pathway, but does not impact myo
      inositol synthesis. Together, these data indicate that IMPL2 functions in the
      histidine biosynthetic pathway, while IMP and IMPL1 catalyze the hydrolysis of
      inositol- and galactose-phosphates in the plant cell. 

PMID- 25620969
TI  - Garlic gamma-glutamyl transpeptidases that catalyze deglutamylation of
      biosynthetic intermediate of alliin.
AB  - S-Alk(en)yl-L-cysteine sulfoxides are pharmaceutically important secondary
      metabolites produced by plants that belong to the genus Allium. Biosynthesis of S
      alk(en)yl-L-cysteine sulfoxides is initiated by S-alk(en)ylation of glutathione,
      which is followed by the removal of glycyl and gamma-glutamyl groups and S
      oxygenation. However, most of the enzymes involved in the biosynthesis of S
      alk(en)yl-L-cysteine sulfoxides in Allium plants have not been identified. In
      this study, we identified three genes, AsGGT1, AsGGT2, and AsGGT3, from garlic
      (Allium sativum) that encode gamma-glutamyl transpeptidases (GGTs) catalyzing the
      removal of the gamma-glutamyl moiety from a putative biosynthetic intermediate of
      S-allyl-L-cysteine sulfoxide (alliin). The recombinant proteins of AsGGT1,
      AsGGT2, and AsGGT3 exhibited considerable deglutamylation activity toward a
      putative alliin biosynthetic intermediate, gamma-glutamyl-S-allyl-L-cysteine,
      whereas these proteins showed very low deglutamylation activity toward another
      possible alliin biosynthetic intermediate, gamma-glutamyl-S-allyl-L-cysteine
      sulfoxide. The deglutamylation activities of AsGGT1, AsGGT2, and AsGGT3 toward
      gamma-glutamyl-S-allyl-L-cysteine were elevated in the presence of the dipeptide
      glycylglycine as a gamma-glutamyl acceptor substrate, although these proteins can
      act as hydrolases in the absence of a proper acceptor substrate, except water.
      The apparent K m values of AsGGT1, AsGGT2, and AsGGT3 for gamma-glutamyl-S-allyl
      L-cysteine were 86 MUM, 1.1 mM, and 9.4 mM, respectively. Subcellular
      distribution of GFP-fusion proteins transiently expressed in onion cells
      suggested that AsGGT2 localizes in the vacuole, whereas AsGGT1 and AsGGT3 possess
      no apparent transit peptide for localization to intracellular organelles. The
      different kinetic properties and subcellular localizations of AsGGT1, AsGGT2, and
      AsGGT3 suggest that these three GGTs may contribute differently to the
      biosynthesis of alliin in garlic. 

PMID- 25620971
TI  - Metabolomics differentiation of canola genotypes: toward an understanding of
      canola allelochemicals.
AB  - Allelopathy is one crop attribute that could be incorporated in an integrated
      weed management system as a supplement to synthetic herbicides. However, the
      underlying principles of crop allelopathy and secondary metabolite production are
      still poorly understood including in canola. In this study, an allelopathic
      bioassay and a metabolomic analysis were conducted to compare three non
      allelopathic and three allelopathic canola genotypes. Results from the laboratory
      bioassay showed that there were significant differences among canola genotypes in
      their ability to inhibit root and shoot growth of the receiver annual ryegrass;
      impacts ranged from 14% (cv. Atr-409) to 76% (cv. Pak85388-502) and 0% (cv. Atr
      409) to 45% (cv. Pak85388-502) inhibition respectively. The root length of canola
      also differed significantly between genotypes, there being a non-significant
      negative interaction (r = -0.71; y = 0.303x + 21.33) between the root length of
      donor canola and of receiver annual ryegrass. Variation in chemical composition
      was detected between organs (root extracts, shoot extracts) and root exudates and
      also between canola genotypes. Root extracts contained more secondary metabolites
      than shoot extracts while fewer compounds were recorded in the root exudates.
      Individual compound assessments identified a total of 14 secondary metabolites
      which were identified from the six tested genotypes. However, only Pak85388-502
      and Av-opal exuded sinapyl alcohol, p-hydroxybenzoic acid and 3,5,6,7,8
      pentahydroxy flavones in agar growth medium, suggesting that the synergistic
      effect of these compounds playing a role for canola allelopathy against annual
      ryegrass in vitro. 

PMID- 25620970
TI  - Comparative genomics of Australian isolates of the wheat stem rust pathogen
      Puccinia graminis f. sp. tritici reveals extensive polymorphism in candidate
      effector genes.
AB  - The wheat stem rust fungus Puccinia graminis f. sp. tritici (Pgt) is one of the
      most destructive pathogens of wheat. In this study, a draft genome was built for
      a founder Australian Pgt isolate of pathotype (pt.) 21-0 (collected in 1954) by
      next generation DNA sequencing. A combination of reference-based assembly using
      the genome of the previously sequenced American Pgt isolate CDL 75-36-700-3 (p7a)
      and de novo assembly were performed resulting in a 92 Mbp reference genome for
      Pgt isolate 21-0. Approximately 13 Mbp of de novo assembled sequence in this
      genome is not present in the p7a reference assembly. This novel sequence is not
      specific to 21-0 as it is also present in three other Pgt rust isolates of
      independent origin. The new reference genome was subsequently used to build a pan
      genome based on five Australian Pgt isolates. Transcriptomes from germinated
      urediniospores and haustoria were separately assembled for pt. 21-0 and
      comparison of gene expression profiles showed differential expression in ~10% of
      the genes each in germinated spores and haustoria. A total of 1,924 secreted
      proteins were predicted from the 21-0 transcriptome, of which 520 were classified
      as haustorial secreted proteins (HSPs). Comparison of 21-0 with two presumed
      clonal field derivatives of this lineage (collected in 1982 and 1984) that had
      evolved virulence on four additional resistance genes (Sr5, Sr11, Sr27, SrSatu)
      identified mutations in 25 HSP effector candidates. Some of these mutations could
      explain their novel virulence phenotypes. 

PMID- 25620972
TI  - Some things get better with age: differences in salicylic acid accumulation and
      defense signaling in young and mature Arabidopsis.
AB  - In Arabidopsis, much of what we know about the phytohormone salicylic acid (SA)
      and its role in plant defense comes from experiments using young plants. We are
      interested in understanding why young plants are susceptible to virulent strains
      of Pseudomonas syringae, while mature plants exhibit a robust defense response
      known as age-related resistance (ARR). SA-mediated signaling is important for
      defense in young plants, however, ARR occurs independently of the defense
      regulators NPR1 and WHY1. Furthermore, intercellular SA accumulation is an
      important component of ARR, and intercellular washing fluids from ARR-competent
      plants exhibit antibacterial activity, suggesting that SA acts as an
      antimicrobial agent in the intercellular space. Young plants accumulate both
      intracellular and intercellular SA during PAMP- and effector-triggered immunity,
      however, virulent P. syringae promotes susceptibility by suppressing SA
      accumulation using the phytotoxin coronatine. Here we outline the hypothesis that
      mature, ARR-competent Arabidopsis alleviates coronatine-mediated suppression of
      SA accumulation. We also explore the role of SA in other mature-plant processes
      such as flowering and senescence, and discuss their potential impact on ARR. 

PMID- 25620973
TI  - Photosynthetic capacity, nutrient status, and growth of maize (Zea mays L.) upon
      MgSO4 leaf-application.
AB  - The major plant nutrient magnesium (Mg) is involved in numerous physiological
      processes and its deficiency can severely reduce the yield and quality of crops.
      Since Mg availability in soil and uptake into the plant is often limited by
      unfavorable soil or climatic conditions, application of Mg onto leaves, the site
      with highest physiological Mg demand, might be a reasonable alternative
      fertilization strategy. This study aimed to investigate, if MgSO4 leaf
      application in practically relevant amounts can efficiently alleviate the effects
      of Mg starvation in maize, namely reduced photosynthesis capacity, disturbed ion
      homeostasis and growth depression. Results clearly demonstrated that Mg
      deficiency could be mitigated by MgSO4 leaf-application as efficiently as by
      resupply of MgSO4 via the roots in vegetative maize plants. Significant increases
      in SPAD values and net rate of CO2-assimilation as well as enhanced shoot biomass
      have been achieved. Ion analysis furthermore revealed an improvement of the
      nutrient status of Mg-deficient plants with regard to [Mg], [K], and [Mn] in
      distinct organs, thereby reducing the risk of Mn-toxicity at the rootside, which
      often occurs together with Mg deficiency on acid soils. In conclusion, foliar
      fertilization with Mg proved to be an efficient strategy to adequately supply
      maize plants with Mg and might hence be of practical relevance to correct
      nutrient deficiencies during the growing season. 

PMID- 25620974
TI  - Organization and regulation of the actin cytoskeleton in the pollen tube.
AB  - Proper organization of the actin cytoskeleton is crucial for pollen tube growth.
      However, the precise mechanisms by which the actin cytoskeleton regulates pollen
      tube growth remain to be further elucidated. The functions of the actin
      cytoskeleton are dictated by its spatial organization and dynamics. However,
      early observations of the distribution of actin filaments at the pollen tube apex
      were quite perplexing, resulting in decades of controversial debate. Fortunately,
      due to improvements in fixation regimens for staining actin filaments in fixed
      pollen tubes, as well as the adoption of appropriate markers for visualizing
      actin filaments in living pollen tubes, this issue has been resolved and has
      given rise to the consensus view of the spatial distribution of actin filaments
      throughout the entire pollen tube. Importantly, recent descriptions of the
      dynamics of individual actin filaments in the apical region have expanded our
      understanding of the function of actin in regulation of pollen tube growth.
      Furthermore, careful documentation of the function and mode of action of several
      actin-binding proteins expressed in pollen have provided novel insights into the
      regulation of actin spatial distribution and dynamics. In the current review, we
      summarize our understanding of the organization, dynamics, and regulation of the
      actin cytoskeleton in the pollen tube. 

PMID- 25620975
TI  - RECQL1 and WRN DNA repair helicases: potential therapeutic targets and
      proliferative markers against cancers.
AB  - RECQL1 and WRN helicases in the human RecQ helicase family participate in
      maintaining genome stability, DNA repair, replication, and recombination pathways
      in the cell cycle. They are expressed highly in rapidly proliferating cells and
      tumor cells, suggesting that they have important roles in the replication of a
      genome. Although mice deficient in these helicases are indistinguishable from
      wild-type mice, their embryonic fibroblasts are sensitive to DNA damage. In tumor
      cells, silencing the expression of RECQL1 or WRN helicase by RNA interference
      induces mitotic catastrophe that eventually kills tumor cells at the mitosis
      stage of the cell cycle. By contrast, the same gene silencing by cognate small
      RNA (siRNA) never kills normal cells, although cell growth is slightly delayed.
      These findings indicate that RECQL1 and WRN helicases are ideal molecular targets
      for cancer therapy. The molecular mechanisms underlying these events has been
      studied extensively, which may help development of anticancer drugs free from
      adverse effects by targeting DNA repair helicases RECQL1 and WRN. As expected,
      the anticancer activity of conventional genotoxic drugs is significantly
      augmented by combined treatment with RECQL1- or WRN-siRNAs that prevents DNA
      repair in cancer cells. In this review, we focus on studies that clarified the
      mechanisms that lead to the specific killing of cancer cells and introduce
      efforts to develop anticancer RecQ-siRNA drugs free from adverse effects. 

PMID- 25620976
TI  - Lupus risk variants in the PXK locus alter B-cell receptor internalization.
AB  - Genome wide association studies have identified variants in PXK that confer risk
      for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or
      lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is
      involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7
      cells, mechanisms linking PXK to lupus pathophysiology have remained undefined.
      In an effort to uncover the mechanism at this locus that increases lupus-risk, we
      undertook a fine-mapping analysis in a large multi-ancestral study of lupus
      patients and controls. We define a large (257kb) common haplotype marking a
      single causal variant that confers lupus risk detected only in European ancestral
      populations and spans the promoter through the 3' UTR of PXK. The strongest
      association was found at rs6445972 with P < 4.62 * 10(-10), OR 0.81 (0.75-0.86).
      Using stepwise logistic regression analysis, we demonstrate that one signal
      drives the genetic association in the region. Bayesian analysis confirms our
      results, identifying a 95% credible set consisting of 172 variants spanning 202
      kb. Functionally, we found that PXK operates on the B-cell antigen receptor
      (BCR); we confirmed that PXK influenced the rate of BCR internalization.
      Furthermore, we demonstrate that individuals carrying the risk haplotype
      exhibited a decreased rate of BCR internalization, a process known to impact B
      cell survival and cell fate. Taken together, these data define a new candidate
      mechanism for the genetic association of variants around PXK with lupus risk and
      highlight the regulation of intracellular trafficking as a genetically regulated
      pathway mediating human autoimmunity. 

PMID- 25620977
TI  - Global diversification of a tropical plant growth form: environmental correlates
      and historical contingencies in climbing palms.
AB  - Tropical rain forests (TRF) are the most diverse terrestrial biome on Earth, but
      the diversification dynamics of their constituent growth forms remain largely
      unexplored. Climbing plants contribute significantly to species diversity and
      ecosystem processes in TRF. We investigate the broad-scale patterns and drivers
      of species richness as well as the diversification history of climbing and non
      climbing palms (Arecaceae). We quantify to what extent macroecological diversity
      patterns are related to contemporary climate, forest canopy height, and
      paleoclimatic changes. We test whether diversification rates are higher for
      climbing than non-climbing palms and estimate the origin of the climbing habit.
      Climbers account for 22% of global palm species diversity, mostly concentrated in
      Southeast Asia. Global variation in climbing palm species richness can be partly
      explained by past and present-day climate and rain forest canopy height, but
      regional differences in residual species richness after accounting for current
      and past differences in environment suggest a strong role of historical
      contingencies in climbing palm diversification. Climbing palms show a higher net
      diversification rate than non-climbers. Diversification analyses of palms
      detected a diversification rate increase along the branches leading to the most
      species-rich clade of climbers. Ancestral character reconstructions revealed that
      the climbing habit originated between early Eocene and Miocene. These results
      imply that changes from non-climbing to climbing habits may have played an
      important role in palm diversification, resulting in the origin of one fifth of
      all palm species. We suggest that, in addition to current climate and
      paleoclimatic changes after the late Neogene, present-day diversity of climbing
      palms can be explained by morpho-anatomical innovations, the biogeographic
      history of Southeast Asia, and/or ecological opportunities due to the
      diversification of high-stature dipterocarps in Asian TRFs. 

PMID- 25620978
TI  - Whole-body transcriptome of selectively bred, resistant-, control-, and
      susceptible-line rainbow trout following experimental challenge with
      Flavobacterium psychrophilum.
AB  - Genetic improvement for enhanced disease resistance in fish is an increasingly
      utilized approach to mitigate endemic infectious disease in aquaculture. In
      domesticated salmonid populations, large phenotypic variation in disease
      resistance has been identified but the genetic basis for altered responsiveness
      remains unclear. We previously reported three generations of selection and
      phenotypic validation of a bacterial cold water disease (BCWD) resistant line of
      rainbow trout, designated ARS-Fp-R. This line has higher survival after infection
      by either standardized laboratory challenge or natural challenge as compared to
      two reference lines, designated ARS-Fp-C (control) and ARS-Fp-S (susceptible). In
      this study, we utilized 1.1 g fry from the three genetic lines and performed RNA
      seq to measure transcript abundance from the whole body of naive and
      Flavobacterium psychrophilum infected fish at day 1 (early time-point) and at day
      5 post-challenge (onset of mortality). Sequences from 24 libraries were mapped
      onto the rainbow trout genome reference transcriptome of 46,585 predicted protein
      coding mRNAs that included 2633 putative immune-relevant gene transcripts. A
      total of 1884 genes (4.0% genome) exhibited differential transcript abundance
      between infected and mock-challenged fish (FDR < 0.05) that included chemokines,
      complement components, tnf receptor superfamily members, interleukins, nod-like
      receptor family members, and genes involved in metabolism and wound healing. The
      largest number of differentially expressed genes occurred on day 5 post-infection
      between naive and challenged ARS-Fp-S line fish correlating with high bacterial
      load. After excluding the effect of infection, we identified 21 differentially
      expressed genes between the three genetic lines. In summary, these data indicate
      global transcriptome differences between genetic lines of naive animals as well
      as differentially regulated transcriptional responses to infection. 

PMID- 25620980
TI  - Biological noise and H2A.Z: a promising connection for language.

PMID- 25620979
TI  - Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia.
AB  - Rendu-Osler-Weber syndrome, also known as hereditary hemorrhagic telangiectasia
      (HHT), is an autosomal dominant vascular disorder. Three genes are causally
      related to HHT: the ENG gene encoding endoglin, a co-receptor of the TGFbeta
      family (HHT1), the ACVRL1 gene encoding ALK1 (activin receptor-like kinase 1), a
      type I receptor of the TGFbeta family (HHT2), and the SMAD4 gene, encoding a
      transcription factor critical for this signaling pathway. Bone morphogenetic
      proteins (BMPs) are growth factors of the TGFbeta family. Among them, BMP9 and
      BMP10 have been shown to bind directly with high affinity to ALK1 and endoglin,
      and BMP9 mutations have recently been linked to a vascular anomaly syndrome that
      has phenotypic overlap with HHT. BMP9 and BMP10 are both circulating cytokines in
      blood, and the current working model is that BMP9 and BMP10 maintain a quiescent
      endothelial state that is dependent on the level of ALK1/endoglin activation in
      endothelial cells. In accordance with this model, to explain the etiology of HHT
      we hypothesize that a deficient BMP9/BMP10/ALK1/endoglin pathway may lead to re
      activation of angiogenesis or a greater sensitivity to an angiogenic stimulus.
      Resulting endothelial hyperproliferation and hypermigration may lead to
      vasodilatation and generation of an arteriovenous malformation (AVM). HHT would
      thus result from a defect in the angiogenic balance. This review will focus on
      the emerging role played by BMP9 and BMP10 in the development of this disease and
      the therapeutic approaches that this opens. 

PMID- 25620981
TI  - Influence of alendronate and endplate degeneration to single level posterior
      lumbar spinal interbody fusion.
AB  - OBJECTIVE: Using alendronate after spinal fusion is a controversial issue due to
      the inhibition of osteoclast mediated bone resorption. In addition, there are an
      increasing number of reports that the endplate degeneration influences the lumbar
      spinal fusion. The object of this retrospective controlled study was to evaluate
      how the endplate degeneration and the bisphosphonate medication influence the
      spinal fusion through radiographic evaluation. METHODS: In this study, 44
      patients who underwent single-level posterior lumbar interbody fusion (PLIF)
      using cage were examined from April 2007 to March 2009. All patients had been
      diagnosed as osteoporosis and would be recommended for alendronate medication.
      Endplate degeneration is categorized by the Modic changes. The solid fusion is
      defined if there was bridging bone between the vertebral bodies, either within or
      external to the cage on the plain X-ray and if there is less than 5 degrees  of
      angular difference in dynamic X-ray. RESULTS: In alendronate group, fusion was
      achieved in 66.7% compared to 73.9% in control group (no medication). Alendronate
      did not influence the fusion rate of PLIF. However, there was the statistical
      difference of fusion rate between the endplate degeneration group and the group
      without endplate degeneration. A total of 52.4% of fusion rate was seen in the
      endplate degeneration group compared to 91.3% in the group without endplate
      degeneration. The endplate degeneration suppresses the fusion process of PLIF.
      CONCLUSION: Alendronate does not influence the fusion process in osteoporotic
      patients. The endplate degeneration decreases the fusion rate.

PMID- 25620982
TI  - Postoperative expansion of dural sac cross-sectional area after unilateral
      laminotomy for bilateral decompression: correlation with clinical symptoms.
AB  - OBJECTIVE: Dural sac cross-sectional area (DSCSA) is a way to measure the degree
      of central spinal canal compression. The objective was to investigate the
      correlation between the expansion ratio of DSCSA after unilateral laminotomy for
      bilateral decompression (ULBD) and the clinical results for lumbar spinal
      stenosis. METHODS: We retrospectively reviewed the clinical data and radiographs
      of 103 patients who underwent ULBD for symptomatic spinal stenosis in one year.
      We compared preoperative and postoperative clinical data and DSCSA and evaluated
      the correlation between clinical and radiographic measurements. RESULTS: There
      was a significant increase of DSCSA after ULBD (p=0.000) and mean expansion ratio
      of DSCSA was 203.7+/-147.2%(range -32.9-826.1%). Clinical outcomes, measured by
      VAS and ODI were improved significantly not only in early postoperative period,
      but also in the last follow-up. However, there were no statistically significant
      correlations between the preoperative DSCSA and clinical symptoms, Perioperative
      expansion ratio of DSCSA and clinical parameters were also not correlated to the
      improvement of clinical symptoms significantly in both early postoperative phase
      and last follow-up. CONCLUSION: Our result indicates that the DSCSA itself has a
      definite limitation to be correlated to the clinical symptoms, and thus
      meticulous correlation between the clinical presentation and MRI imaging is
      essential in determination of surgical treatment.

PMID- 25620983
TI  - Effectiveness of Repeated Radiofrequency Neurotomy for Facet joint Syndrome after
      Microscopic Discectomy.
AB  - OBJECTIVE: Postoperative facet joint syndrome requiring radiofrequency neurotomy
      (RFN) is a relatively common problem following microscopic discectomy. However,
      the efficacy of repeated RFN after microscopic discectomy has not been clearly
      documented. The purpose of this study was to determine the success rate and
      symptom-free duration of repeated RFN for facet joint syndrome after microscopic
      discectomy. METHODS: Medical records from 56 patients, who had undergone
      successful initial RFN following microscopic discectomy, experienced recurrence
      of pain, and subsequently had repeated RFN, were reviewed and evaluated.
      Responses of repeated RFN were compared with initial radiofrequency neurotomy for
      success rates and duration of relief. The criterion for RFN to be successful was
      defined as greater than 50% relief from pain and sufficient satisfaction of
      patients with prior RFN to have repeated RFN. RESULTS: Fifty-six patients (41
      women and 15 men; mean age=48 years) had repeated RFNs, which were successful in
      all except three patients. RFN denervated three bilateral segments (L3-L4, L4-L5,
      and L5-S1) in all patients. Mean duration of relief after initial RFN was 9.2
      months (range 3-14). The mean duration of relief after secondary RFN in 53
      patients was 9.0 months (range 4-14). The success rates and duration of relief
      remained consistent after subsequent RFNs. CONCLUSION: Repeated RFN for lumbar
      facet joint pain after microscopic discectomy is an effective palliative
      treatment. It provided a mean duration of relief of 9.0 months and >94% success
      rate.

PMID- 25620984
TI  - Spontaneous regression of cervical disc herniation: a case report.
AB  - Spontaneous regression of cervical disc herniation is a rare, and such reports
      are few. A 39 year-old woman complained of severe neck pain associated with
      tingling and numbness of right upper extremity. The MRI of the cervical spine
      revealed a posterior disc extrusion at the C4-C5 level in the right para-central
      location. The patient was treated with conservative management without any
      surgical treatment. The patient's symptoms were significant improvement. After
      two years later, we performed follow-up cervical MRI that revealed significant
      spontaneous regression of the C4-C5 intervertebral disc extrusion. 

PMID- 25620985
TI  - Fatal Rhabdomyolysis following Spine Surgery in a Morbidly Obese Patient: A Case
      Report.
AB  - We generally believe that obese patients are faced on higher risk of developing
      perioperative complications. Rhabdomyolysis is a rare but potentially life
      threatening condition caused by the release of injured skeletal muscle components
      into the circulation. It usually results from mechanical damage to the muscle,
      intoxication, or a postictal state after a seizure. In the present study, we have
      reported a rare case of rhabdomyolysis developing in a morbidly obese patient
      after upper thoracic spinal fusion surgery. We have found acute renal failure
      that evolved during the course of treatment resulted in a fatal outcome even
      though the patient received intensive supportive care. Our experience suggests
      that this rare complication should be considered in morbidly obese patients and
      those efforts should be made to avoid rhabdomyolysis. 

PMID- 25620986
TI  - Migration of rod into retroperitoneal region: a case report and review of the
      literature.
AB  - Spinal stabilization with fusion is the widely used method for traumatic or
      pathologic fracture of spine, spinal stenosis, and spondylolisthesis.
      Complications may emerge during or after the operations. Infection, hematoma and
      neurological deficits are early noticed findings. Screw and/or rod fractures
      present in long-term after surgery. Rod migration in out of the spinal column is
      a rare entity. A 67-year-old woman was visited our clinic for right leg pain. She
      had a previous spinal instrumentation surgery for spondylolisthesis in another
      center 6 years before. After radiological work-up, a distally migrated rod piece
      was observed in the retroperitoneal portion. The patient was operated for
      degenerative change; old instruments were replaced and extended to the L2 level
      with posterior spinal fusion. After the operation, her right leg pain improved.
      The asymptomatic migrated rod piece has regularly been followed clinically and
      radiologically, since then. Although it has rarely been reported, migration of
      the instrumentation material should be kept in mind. Spinal fixation without
      fusion makes the mechanical system vulnerable to motion effects of spine,
      especially in a degenerative and osteoporotic background. Long-term, even life
      long follow-up is necessary for late term complications. 

PMID- 25620987
TI  - Lumbar disc herniation in a patient with congenital vertebral body anomaly: a
      case report.
AB  - Lumbar disc herniation is characterized with low back and leg pain resulting from
      the degenerated lumbar disc compressing the spinal nerve root. The etiology of
      degenerative spine is related to age, smoking, microtrauma, obesity, disorders of
      familial collagen structure, occupational and sports-related physical activity.
      However, disc herniations induced by congenital lumbar vertebral anomalies are
      rarely seen. Vertebral fusion defect is one of the causes of congenital
      anomalies. The pathogenesis of embryological corpus vertebral fusion anomaly is
      not fully known. In this paper, a 30-year-old patient who had the complaints of
      low back and right leg pain after falling from a height is presented. She had
      right L5-S1 disc herniation that had developed on the basis of S1 vertebra corpus
      fusion anomaly in Lumbar computed tomography. This case has been discussed in the
      light of literature based on evaluations of Lumbar Computed Tomography (CT) and
      Magnetic Resonance Imaging (MRI). This case is unique in that it is the first
      case with development of lumbar disc herniation associated with S1 vertebral
      corpus fusion anomaly. Congenital malformations with unusual clinical
      presentation after trauma should be evaluated through advanced radiological
      imaging techniques. 

PMID- 25620988
TI  - Aneurysmal bone cysts of the spine: two case reports.
AB  - Aneurysmal bone cysts are rare entities which causes expansile and destructive
      bone lesions characterized by reactive proliferation of connective tissue. They
      usually grow rapidly with hypervascularity. In clinical practice they can be
      easily misdiagnosed due to the rare occurance and having no such typical findings
      as radiologically. Most cases have uncommon pain symptoms, but rarely, if
      fractures occur, neurological findings can be seen and the surgical treatment, if
      needed, could be difficult. We will discuss our evaluations to two cases that we
      experienced in our clinic in this report. 

PMID- 25620989
TI  - Spinal paraganglioma adherent to the cauda equina.
AB  - Paragangliomas are rare among intradural spinal tumors. Most of them are benign,
      but aggressive behavior and local recurrence can occur. Cases of paraganglioma
      are, difficult to diagnose radiologically; hence, diagnosis is confirmed
      histopathologically. Radiologically, paragangliomas are similar to ependymomas,
      and, histopathologically, they are similar to neuroendocrine tumors. We evaluated
      the case of a 76-year-old woman with a spinal paraganglioma that was associated
      with back pain and radiating pain in both the lower extremities. She underwent an
      operation, and her symptoms were relieved. Here, we describe a rare case of
      paraganglioma that was adherent to the cauda equina. 

PMID- 25620990
TI  - Lumbar disc herniations 'to operate or not' patient selection and timing of
      surgery.
AB  - At times lumbar disc herniations present a quandary to the spine surgeon in
      regards to the most appropriate intervention and a need to optimize medical and
      surgical therapies. We discuss a case of ours and our experience in treating this
      common spinal pathology, along with a commentary on the article published by Kim
      et al. entitled 'Spontaneous regression of extruded lumbar disc herniation: three
      cases report in Korean J Spine. 2013 Jun;10(2):78-81.' 

PMID- 25620991
TI  - Intramedullary spinal neuorocysticercosis.

PMID- 25620992
TI  - Noncontiguous multiple spinal tuberculosis.

PMID- 25620993
TI  - Consumer familiarity, perspectives and expected value of personalized medicine
      with a focus on applications in oncology.
AB  - AIMS: Knowledge of consumer perspectives of personalized medicine (PM) is
      limited. Our study assessed consumer perspectives of PM, with a focus on oncology
      care, to inform industry, clinician and payer stakeholders' programs and policy.
      MATERIALS & METHODS: A nationally representative survey of 602 US consumers' >=30
      years old explored familiarity, perspectives and expected value of PM. RESULTS:
      Most (73%) respondents have not heard of 'personalized medicine,' though after
      understanding the term most (95%) expect PM to have a positive beneft. Consumer's
      willingness to pay is associated with products' impact on survival, rather than
      predicting disease risk. If testing indicates consumers are not candidates for
      oncology therapies, most (84%) would seek a second opinion or want therapy
      anyway. CONCLUSIONS: Understanding heterogeneity in consumer perspectives of PM
      can inform program and policy development.

PMID- 25620994
TI  - The immune response after fracture trauma is different in old compared to young
      patients.
AB  - BACKGROUND: Despite significant medical progress and improved treatment, surgical
      procedures of proximal femur fractures in older patients are still associated
      with a high postoperative complication and mortality rate. Recently, several
      authors investigated the phenomenon of immunoageing, indicating differences in
      the ageing immune system. The aim of the present multi-center prospective
      clinical trial was to analyze differences in the posttraumatic immune response of
      old patients compared to young patients. METHODS: Blood was collected from young
      patients (<50 y, n = 20) with long bone fractures (YF), old patients (>70 y, n =
      21) with proximal femur fractures (OF) upon clinical admission and within 6 hours
      after surgery, and two healthy age matched control groups (YH & OH). Serum TRAIL-
      and cytokine concentrations were analyzed via cytometric bead array, Fas-Ligand
      and TNF-Receptor-I via ELISA. CD15(+) magnetic bead-isolated neutrophils (PMN)
      were TUNEL stained. RESULTS: IL-6 was significantly increased only in OF after
      trauma and surgery whereas YF patient exhibited a marked decrease of TNF after
      trauma. Interestingly, a significant increase of GM-CSF serum levels was observed
      in YF only, whereas OF exhibited a decrease of systemic IFN-gamma concentrations
      after trauma and after surgery. The healthy controls, old and young, had more or
      less similar inflammation levels. Moreover, TRAIL serum levels were diminished in
      OF after trauma and even further after surgery whereas in YF this was only
      observed after the surgical procedure. Fas-L concentrations were reduced only in
      YF after surgery or trauma. PMN apoptosis was significantly reduced only in YF,
      indicating activation of the innate immune system. DISCUSSION: In summary, our
      data suggest that the posttraumatic immune response is differently regulated in
      old and young trauma patients. The operative procedure further impacts these
      differences after trauma. Whether the decreased activation of PMNs and phagocytes
      along with the observed dysregulation of the posttraumatic inflammatory response
      contributes to the high perioperative mortality rate of the elderly suffering
      from a proximal femoral fracture requires further investigation.

PMID- 25620995
TI  - Parenting Deficits of Mothers Living with HIV/AIDS who have Young Children.
AB  - The purpose of this study was to examine a model of the relationships between
      parenting deficits and skills, along with child outcomes, in a sample of mothers
      living with HIV (MLH) and their 6 to 14 year old children. Sixty-two MLH (61%
      Latina, 26% black, 3% white, & 10% multiracial) and their well children (age 6 -
      14) were recruited from the greater Los Angeles, California, region to
      participate in an intervention (IMAGE: Improving Mothers' parenting Abilities,
      Growth, and Effectiveness) designed to assist MLH with parenting and self-care
      skills. Constructs examined included parenting deficits, parenting skills, and
      child outcomes. Covariance structural modeling was used for the analyses.
      Covariance structural modeling confirmed the hypothesized set of construct
      associations. As predicted, fewer parenting deficits were associated with better
      parenting skills, which, in turn, were associated with better child outcomes.
      This study delineated further the parenting issues with which MLH struggle,
      providing information on the interventions needed for this population. MLH who
      have little confidence they can enact parenting skills and limited knowledge of
      basic parenting practices appear to be less likely to provide family routines
      consistently, monitor their children, or to engender family cohesion or a close
      parent-child relationship. Such parenting skills were found to be associated with
      child functioning.

PMID- 25620998
TI  - Could boosting the oligoadenylate synthetase-like pathway bring a new era of
      antiviral therapy?

PMID- 25620996
TI  - Candidate gene-environment interaction research: reflections and recommendations.
AB  - Studying how genetic predispositions come together with environmental factors to
      contribute to complex behavioral outcomes has great potential for advancing the
      understanding of the development of psychopathology. It represents a clear
      theoretical advance over studying these factors in isolation. However, research
      at the intersection of multiple fields creates many challenges. We review several
      reasons why the rapidly expanding candidate gene-environment interaction (cG*E)
      literature should be considered with a degree of caution. We discuss lessons
      learned about candidate gene main effects from the evolving genetics literature
      and how these inform the study of cG*E. We review the importance of the
      measurement of the gene and environment of interest in cG*E studies. We discuss
      statistical concerns with modeling cG*E that are frequently overlooked.
      Furthermore, we review other challenges that have likely contributed to the cG*E
      literature being difficult to interpret, including low power and publication
      bias. Many of these issues are similar to other concerns about research integrity
      (e.g., high false-positive rates) that have received increasing attention in the
      social sciences. We provide recommendations for rigorous research practices for
      cG*E studies that we believe will advance its potential to contribute more
      robustly to the understanding of complex behavioral phenotypes. 

PMID- 25621000
TI  - Prevalence and determinant factors of exclusive breastfeeding practices among
      mothers in Enderta woreda, Tigray, North Ethiopia: a cross-sectional study.
AB  - BACKGROUND: In Ethiopia national breastfeeding practice is poor because of
      traditional and cultural beliefs, low educational levels, heavy workload of
      mothers, poor sanitary conditions, type of assistance at delivery, duration of
      stay at home, ethnicity, poor maternal knowledge, age, parity, antenatal service
      utilization and place of delivery. This study is aimed to assess the prevalence
      and determinants of exclusive breastfeeding practice in mothers in Enderta woreda
      (district), Ethiopia. METHODS: A community based cross-sectional study with
      multistage sampling method was used to select 541 mothers with children less than
      24 months of age in Enderta woreda. Data was collected by administered structured
      questionnaire. Bivariate and Multivariable logistic regression was used to check
      the associations and controlling confounding variables. RESULT: A total of 530
      mothers were included with a response rate 98%. The mean (+/- SD) age of the
      mothers was 26.9 (+/- 5.98) years. Majority of the mothers (70.2%) were practiced
      exclusive breastfeeding. Age of the mother (AOR 0.12; 95% CI: 0.02, 0.97), age of
      the child (AOR 0.52 95% CI: 0.27, 0.99) and postnatal care (AOR; 2.68; 95% CI:
      1.44, 4.98) were found statistically significant with exclusive breastfeeding.
      CONCLUSION: The prevalence rate of exclusive breastfeeding was high in Enderta
      woreda. The age of the mother, age of the child and receiving postnatal care were
      the determinant factors for exclusive breastfeeding in the study area.

PMID- 25621001
TI  - The bumpy road to implementing the Baby-Friendly Hospital Initiative in Austria:
      a qualitative study.
AB  - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI) aims to promote and
      support breastfeeding. Globally, around 20,000 facilities have been designated
      Baby-Friendly. In Austria, however, only 16% of the maternity units have received
      BFHI-certification. Internationally, few studies have investigated facilitating
      or hindering factors for BFHI implementation. The need to extend BFHI
      certification rates has been investigated previously, but little is known about
      why maternity units decide to become BFHI-certified, how BFHI is installed at the
      unit level, and which factors facilitate or impede the operation of the BFHI in
      Austria and how barriers are overcome. METHODS: Using a qualitative approach,
      (health) professionals' perceptions of the selection, installation, as well as
      facilitators of and barriers to the BFHI were investigated. 36 semi-structured
      interviews with persons responsible for BFHI implementation (midwives, nurses,
      physicians, quality manager) were conducted in three Austrian maternity units.
      Data were analyzed using thematic analysis. RESULTS: Interviewees mentioned
      several motives for selecting the BFHI, including BFHI as a marketing tool,
      improvement of existing services, as well as collaboration between different
      professional groups. In each hospital, "change agents" were identified, who
      promoted the BFHI, teamed up with the managers of other professional groups and
      finally, with the manager of the unit. Installation of BFHI involved the adoption
      of project management, development and dissemination of new standards, and
      training of all staff. Although multiple activities were planned to prepare for
      actually putting the BFHI into practice, participants mentioned not only
      facilitating, but also several hindering factors. Interpretations of what
      facilitated or impeded the operation of BFHI differed among and between
      professional groups. CONCLUSION: Successful implementation of the BFHI in Austria
      depends on a complex interplay of multiple factors including a consensual "bottom
      up" selection process, followed by a multifaceted installation stage. Even these
      activities may be perceived as a hindrance for non-BFHI-certified hospitals.
      Findings also suggest that despite active preparation, several barriers have to
      be overcome when BFHI is actually incorporated into routine practices. BFHI seems
      to pose a great challenge to health professionals' work routines and, thus, clear
      structural changes of such routines as well as ongoing monitoring and support
      activities are required.

PMID- 25620999
TI  - Novel drugs targeting Toll-like receptors for antiviral therapy.
AB  - Toll-like receptors (TLRs) are sentinel receptors of the host innate immune
      system that recognize conserved 'pathogen-associated molecular patterns' of
      invading microbes, including viruses. The activation of TLRs establishes
      antiviral innate immune responses and coordinates the development of long-lasting
      adaptive immunity in order to control viral pathogenesis. However, microbe
      induced damage to host tissues may release 'danger-associated molecular patterns'
      that also activate TLRs, leading to an overexuberant inflammatory response and,
      ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as
      therapeutics for the treatment of viral infections that result in inflammatory
      damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we
      explore recent advances in TLR biology with a focus on novel drugs that target
      TLRs (agonists and antagonists) for antiviral therapy.

PMID- 25621002
TI  - High-Speed Coherent Raman Fingerprint Imaging of Biological Tissues.
AB  - An imaging platform based on broadband coherent anti-Stokes Raman scattering
      (BCARS) has been developed which provides an advantageous combination of speed,
      sensitivity and spectral breadth. The system utilizes a configuration of laser
      sources that probes the entire biologically-relevant Raman window (500 cm-1 to
      3500 cm-1) with high resolution (< 10 cm-1). It strongly and efficiently
      stimulates Raman transitions within the typically weak "fingerprint" region using
      intrapulse 3-colour excitation, and utilizes the nonresonant background (NRB) to
      heterodyne amplify weak Raman signals. We demonstrate high-speed chemical imaging
      in two- and three-dimensional views of healthy murine liver and pancreas tissues
      and interfaces between xenograft brain tumours and the surrounding healthy brain
      matter.

PMID- 25621003
TI  - High prevalence of hpv multiple genotypes in women with persistent chlamydia
      trachomatis infection.
AB  - BACKGROUND: Chlamydia trachomatis interaction with HR-HPV types has highlighted a
      central role in cervical cancer development. The aim of this study was to
      investigate HPV prevalence and genotypes distribution in women at risk for C.
      trachomatis infection and negative for intraepithelial lesion or malignancy.
      METHODS: 1071 cervical swabs were tested for C. trachomatis by Real Time PCR and
      genotyping by ompA gene sequencing. Additionally, a quantitative Real time-PCR
      was performed to assess the expression of the C. trachomatis Hsp60-encoding gene
      (Ct604 portion), linked to a persistent status of infection. HPV infection and
      genotypes was investigated in C. trachomatis positive women using Luminex
      technology. RESULTS: C. trachomatis infection was detected in 53 out of 1071
      (4.5%) samples, of which the 53% resulted positive for Hsp60 gene expression. The
      overall prevalence of HPV infection in C. trachomatis positive samples was of
      60.4% (32/53): in 37.5% of samples was present a single genotype, while multiple
      genotypes infections were found in the 62.5% of them. Among women with a C.
      trachomatis chronic infection, 68% were HPV co-infected and the 79% showed
      multiple genotypes. Should be noted that levels of C. trachomatis Hsp60
      expression in HPV co-infected women were significantly lower compared to women
      infected only with C. trachomatis. The C. trachomatis serotype F was found in the
      majority of samples, independently of HPV infection. CONCLUSIONS: A high
      prevalence of HPV multiple infections have been found in young women affected
      with a C. trachomatis chronic infection. These observations suggested that the
      expression of CHSP60-1, interfering with both apoptotic and cellular senescence
      pathways, may promote a favourable local microenvironment for HPV infection.

PMID- 25621004
TI  - Psychosocial factors are preventive against coronary events in Japanese men with
      coronary artery disease: The Eastern Collaborative Group Study 7.7-year follow-up
      experience.
AB  - BACKGROUND: The Japanese Coronary-prone Behaviour Scale (JCBS) is a questionnaire
      developed by the Eastern Collaborative Group Study (ECGS), a multi-centre study
      of coronary-prone behaviour among Japanese men. Subscale C of the JCBS consists
      of 9 items that have been independently associated with the presence of coronary
      artery disease (CAD) in patients undergoing coronary angiography (CAG). There
      have been no reports of a relationship between any behavioural factor and the
      prognosis of CAD in Japan. The purpose of the current study was to investigate
      behavioural correlations with the prognosis of CAD as a part of the ECGS.
      METHODS: We examined the mortality and coronary events of 201 men (58 +/- 10, 27
      86 years) enrolled in the ECGS from 1990 to 1995, who underwent diagnostic
      coronary angiography and were administered the JCBS and the Japanese version of
      the Jenkins Activity Survey (JAS) Form C. Their health information after CAG was
      determined by a review of their medical records and by telephone interviews that
      took place from 2002 to 2003. RESULTS: Cardiac events during the follow-up period
      (7.7 +/- 4.2 years) included 13 deaths from CAD, 25 cases of new-onset myocardial
      infarction, 26 cases of percutaneous coronary intervention, and 19 cases of
      coronary artery bypass graft surgery. There was no difference in established risk
      factors between groups with and without cardiac events. Seven factors were
      extracted by principal component analysis in order to clarify which factors were
      measured by the JCBS. Stepwise multivariate Cox-hazard regression analysis, in
      which 9 standard coronary risk factors were forced into the model, showed that
      Factor 4 from the JCBS (namely, the Japanese spirit of 'Wa') was independently
      associated with coronary events (hazard ratio: 0.21; p = 0.01). By other Cox
      hazards regression analyses of coronary events using each set of JAS scores and
      the JCBS Scale C score instead of Factor 4 as selectable variables, the JAS
      scores or the JCBS Scale C score were not entered into the models. CONCLUSION:
      The Japanese spirit of 'Wa' is a preventive factor against coronary events for
      Japanese men with CAD.

PMID- 25621005
TI  - Mixed methods evaluation of well-being benefits derived from a heritage-in-health
      intervention with hospital patients.
AB  - BACKGROUND: This study sought to determine the effects of a heritage-in-health
      intervention on well-being. Benefits of arts-in-health interventions are
      relatively well-documented yet little robust research has been conducted using
      heritage-in-health interventions, such as those involving museum objects.
      METHODS: Hospital patients (n = 57) participated in semi-structured, 30-40 minute
      facilitated interview sessions, discussing and handling museum objects comprising
      selections of six artefacts and specimens loaned from archaeology, art, geology
      and natural history collections. Well-being measures (Positive Affect Negative
      Affect Scale, Visual Analogue Scales) evaluated the sessions while inductive and
      deductive thematic analysis investigated psycho-educational features accounting
      for changes. RESULTS: Comparison of pre- and post-session quantitative measures
      showed significant increases in well-being and happiness. Qualitative
      investigation revealed thinking and meaning-making opportunities for participants
      engaged with objects. CONCLUSIONS: Heritage-in-health sessions enhanced positive
      mood and social interaction, endorsing the need for provision of well-being
      related museum and gallery activities for socially excluded or vulnerable
      healthcare audiences.

PMID- 25621006
TI  - Combined endothelial and epithelial barrier disruption of the colon may be a
      contributing factor to the Ebola sepsis-like syndrome.
AB  - After an initial febrile viral syndrome, infection with Ebola virus often induces
      an explosive late "Ebola sepsis-like syndrome" which appears very similar to some
      phenotypes of bacterial sepsis and is commonly fatal. It is possible that direct
      and diffuse viral infection of both the endothelium and epithelium of the colon
      may cause sufficient disruption of both the endothelial and epithelial barriers
      to induce exposure or leakage of endotoxin and bacterial antigens to, or into,
      the vascular system precipitating or exacerbating the Ebola sepsis-like syndrome.
      If colonic barrier disruption or vascular exposure of bacterial antigens from the
      colon is found to comprise an important mechanism of the Ebola sepsis-like
      syndrome, protocolized timed decontamination of the bowel with or without timed
      prophylactic antibiotics might warrant investigation. 

PMID- 25620997
TI  - Sleep, cognition, and normal aging: integrating a half century of
      multidisciplinary research.
AB  - Sleep is implicated in cognitive functioning in young adults. With increasing
      age, there are substantial changes to sleep quantity and quality, including
      changes to slow-wave sleep, spindle density, and sleep continuity/fragmentation.
      A provocative question for the field of cognitive aging is whether such changes
      in sleep physiology affect cognition (e.g., memory consolidation). We review
      nearly a half century of research across seven diverse correlational and
      experimental domains that historically have had little crosstalk. Broadly
      speaking, sleep and cognitive functions are often related in advancing age,
      though the prevalence of null effects in healthy older adults (including
      correlations in the unexpected, negative direction) indicates that age may be an
      effect modifier of these associations. We interpret the literature as suggesting
      that maintaining good sleep quality, at least in young adulthood and middle age,
      promotes better cognitive functioning and serves to protect against age-related
      cognitive declines. 

PMID- 25621007
TI  - Understanding how colorectal units achieve short length of stay: an interview
      survey among representative hospitals in England.
AB  - BACKGROUND: Wide variation in the outcomes of colorectal surgery persists,
      despite a well-established evidence-base to inform clinical practice. This
      variation may be attributed to differences in quality of care, but we do not know
      what this means in practical terms of care delivery. This telephone interview
      study aimed to identify distinguishing characteristics in the organisation of
      care among colorectal units with the best length of stay results in England.
      METHODS: Ten English National Health Service hospitals were identified with the
      shortest length of stay after elective colonic surgery between January 2011 and
      December 2012. Semi-structured telephone interviews were conducted with a senior
      colorectal surgeon and ward nurse, who were not informed of their performance, at
      each site. Audio recordings were professionally transcribed and thematically
      analysed for similarities and differences in practice between units. RESULTS: All
      ten short length of stay units approached agreed to participate, and 19 of 20
      interviews were recorded. These units standardised clinical care based upon an
      Enhanced Recovery Program. Beyond this, they organised the clinical team to
      efficiently and reliably deliver this package of care, with the majority of day
      to-day care delivered by consultants and nurses. Patients were closely monitored
      for postoperative deterioration, using a combination of early warning scores,
      nurses' clinical judgement and regular senior medical review. Of note, operative
      volume and laparoscopy rates in these units were not statistically significantly
      different from the national average (p = 0.509 and p = 0.131, respectively). The
      postoperative analgesic strategy varied widely between units, from routine
      epidural use to local anaesthetic infiltration or patient-controlled analgesia.
      CONCLUSIONS: The Enhanced Recovery Program may be seen as necessary but not
      sufficient to achieve the best length of stay results. In the study units,
      consultants and nurses led and delivered the majority of patient care on the
      ward. High quality teamwork helped detect and resolve clinical issues promptly,
      with nurses empowered to contact consultants directly if needed. Other units may
      learn from these teams by adopting protocol-based, consultant- or nurse-delivered
      care, and by improving coordination and communication between consultants and
      ward nurses.

PMID- 25621008
TI  - Complications and salvage options after laser lithotripsy for a vesical calculus
      in a tetraplegic patient: a case report.
AB  - BACKGROUND: Laser lithotripsy of vesical calculi in tetraplegic subjects with
      long-term urinary catheters is fraught with complications because of bladder wall
      oedema, infection, fragile urothelium, bladder spasms, and autonomic dysreflexia.
      Severe haematuria should be anticipated; failure to institute measures to
      minimise bleeding and prevent clot retention can be catastrophic. We present an
      illustrative case. CASE PRESENTATION: A tetraplegic patient underwent laser
      lithotripsy of vesical stone under general anaesthesia. During lithotripsy,
      severe bladder spasms and consequent rise in blood pressure occurred. Bleeding
      continued post-operatively resulting in clot retention. CT revealed clots within
      distended but intact bladder. Clots were sucked out and continuous bladder
      irrigation was commenced. Bleeding persisted; patient developed repeated clot
      retention. Cystoscopy was performed to remove clots. Patient developed abdominal
      distension. Bladder rupture was suspected; bed-side ultrasound scan revealed
      diffuse small bowel dilatation with mild peritoneal effusion; under-filled
      bladder containing small clot. Patient developed massive abdominal distension and
      ileus. Two days later, CT with oral positive contrast revealed intra-peritoneal
      haematoma at the dome of bladder with perforation at the site of haematoma. Free
      fluid was noted within the peritoneal cavity. This patient was managed by gastric
      drainage and intravenous fluids. Patient's condition improved gradually with
      urethral catheter drainage. Follow-up CT revealed resolution of bladder rupture,
      perivesical haematoma, and intra-peritoneal free fluid. CONCLUSION: If bleeding
      occurs, bladder irrigation should be commenced immediately after surgery to
      prevent clot retention. When bladder rupture is suspected, CT of abdomen should
      be done instead of ultrasound scan, which may not reveal bladder perforation. It
      is debatable whether laparotomy and repair of bladder rupture is preferable to
      nonoperative management in tetraplegics. Anti-muscarinic drugs should be
      prescribed prior to lithotripsy to control bladder spasms; aspirin and ibuprofen
      should be omitted. If significant bleeding occurs during lithotripsy, procedure
      should be stopped and rescheduled. Percutaneous cystolithotripsy using a wide
      channel could be quicker to clear stones, as larger fragments could be retrieved;
      lesser stimulant for triggering autonomic dysreflexia, as it avoids urethral
      manipulation. But in patients with small, contracted bladder, and protuberant
      abdomen, percutaneous access to urinary bladder may be difficult and can result
      in injury to bowels.

PMID- 25621009
TI  - Compartment elasticity measured by pressure-related ultrasound to determine
      patients "at risk" for compartment syndrome: an experimental in vitro study.
AB  - BACKGROUND: 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. METHODS: In an in vitro model, using
      an artificial container simulating dimensions of the human anterior tibial
      compartment, intra-compartmental pressures (p) were raised subsequently up to 80
      mmHg by infusion of saline solution. The compartmental depth (mm) in the cross
      section view was measured before and after manual probe compression (100 mmHg)
      upon the surface resulting in a linear compartmental displacement (?d). 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 (mmHg) occurred. The Pearson coefficient showed a high
      correlation (r(2) = -0.960). The intra-observer 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.

PMID- 25621010
TI  - Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an
      accelerated phase-chronic myeloid leukemia case.
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is genetically characterized by the
      occurrence of a reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL
      gene fusion on the derivative chromosome 22, i.e. the Philadelphia (Ph)
      chromosome. During CML progression 60-80% of the cases acquire additional genetic
      changes. Even though hyperdiploidy is not a rare finding in advanced phase-CML,
      hyperdiploidy together with a T315I kinase domain (KD) mutation in the BCR-ABL
      gene has not yet been reported. RESULTS: A complete cytogenetic and molecular
      cytogenetic analysis; molecular biology methods such as quantitative reverse
      transcription polymerase chain reaction (RQ-PCR) and allele-specific
      oligonucleotide (ASO)-PCR; and immunophenotypically confirmed CML in acceleration
      phase (AP). Our case revealed the presence of hyperdiploidy including multiple
      copies of the Ph chromosome, presence of b3a2 fusion transcript,T315I mutation in
      BCR-ABL KD in pre imatinib mesylate (IM) treatment. The ratio of BCR-ABL/ABL
      expression in post nilotinib treatment was 0.07% on international scale.
      CONCLUSIONS: The patient demonstrated a good response to nilotinib after imatinib
      failure; while the hyperdiploid clone disappeared the T315I mutation remained
      during follow-up. The underlying mechanisms and prognostic implications of these
      cytogenetic abnormalities are discussed.

PMID- 25621011
TI  - Performance of genetic programming optimised Bowtie2 on genome comparison and
      analytic testing (GCAT) benchmarks.
AB  - BACKGROUND: Genetic studies are increasingly based on short noisy next generation
      scanners. Typically complete DNA sequences are assembled by matching short
      NextGen sequences against reference genomes. Despite considerable algorithmic
      gains since the turn of the millennium, matching both single ended and paired end
      strings to a reference remains computationally demanding. Further tailoring
      Bioinformatics tools to each new task or scanner remains highly skilled and
      labour intensive. With this in mind, we recently demonstrated a genetic
      programming based automated technique which generated a version of the state-of
      the-art alignment tool Bowtie2 which was considerably faster on short sequences
      produced by a scanner at the Broad Institute and released as part of The Thousand
      Genome Project. RESULTS: Bowtie2 (G P) and the original Bowtie2 release were
      compared on bioplanet's GCAT synthetic benchmarks. Bowtie2 (G P) enhancements
      were also applied to the latest Bowtie2 release (2.2.3, 29 May 2014) and retained
      both the GP and the manually introduced improvements. CONCLUSIONS: On both
      singled ended and paired-end synthetic next generation DNA sequence GCAT
      benchmarks Bowtie2GP runs up to 45% faster than Bowtie2. The lost in accuracy can
      be as little as 0.2-0.5% but up to 2.5% for longer sequences.

PMID- 25621012
TI  - Selective impairment of methylation maintenance is the major cause of DNA
      methylation reprogramming in the early embryo.
AB  - BACKGROUND: DNA methylomes are extensively reprogrammed during mouse pre
      implantation and early germ cell development. The main feature of this
      reprogramming is a genome-wide decrease in 5-methylcytosine (5mC). Standard high
      resolution single-stranded bisulfite sequencing techniques do not allow
      discrimination of the underlying passive (replication-dependent) or active
      enzymatic mechanisms of 5mC loss. We approached this problem by generating high
      resolution deep hairpin bisulfite sequencing (DHBS) maps, allowing us to follow
      the patterns of symmetric DNA methylation at CpGs dyads on both DNA strands over
      single replications. RESULTS: We compared DHBS maps of repetitive elements in the
      developing zygote, the early embryo, and primordial germ cells (PGCs) at defined
      stages of development. In the zygote, we observed distinct effects in paternal
      and maternal chromosomes. A significant loss of paternal DNA methylation was
      linked to replication and to an increase in continuous and dispersed
      hemimethylated CpG dyad patterns. Overall methylation levels at maternal copies
      remained largely unchanged, but showed an increased level of dispersed hemi
      methylated CpG dyads. After the first cell cycle, the combined DHBS patterns of
      paternal and maternal chromosomes remained unchanged over the next three cell
      divisions. By contrast, in PGCs the DNA demethylation process was continuous, as
      seen by a consistent decrease in fully methylated CpG dyads over consecutive cell
      divisions. CONCLUSIONS: The main driver of DNA demethylation in germ cells and in
      the zygote is partial impairment of maintenance of symmetric DNA methylation at
      CpG dyads. In the embryo, this passive demethylation is restricted to the first
      cell division, whereas it continues over several cell divisions in germ cells.
      The dispersed patterns of CpG dyads in the early-cleavage embryo suggest a
      continuous partial (and to a low extent active) loss of methylation apparently
      compensated for by selective de novo methylation. We conclude that a combination
      of passive and active demethylation events counteracted by de novo methylation
      are involved in the distinct reprogramming dynamics of DNA methylomes in the
      zygote, the early embryo, and PGCs.

PMID- 25621013
TI  - Transcription-coupled recruitment of human CHD1 and CHD2 influences chromatin
      accessibility and histone H3 and H3.3 occupancy at active chromatin regions.
AB  - BACKGROUND: CHD1 and CHD2 chromatin remodeling enzymes play important roles in
      development, cancer and differentiation. At a molecular level, the mechanisms are
      not fully understood but include transcriptional regulation, nucleosome
      organization and turnover. RESULTS: Here we show human CHD1 and CHD2 enzymes co
      occupy active chromatin regions associated with transcription start sites (TSS),
      enhancer like regions and active tRNA genes. We demonstrate that their
      recruitment is transcription-coupled. CHD1 and CHD2 show distinct binding
      profiles across active TSS regions. Depletion of CHD1 influences chromatin
      accessibility at TSS and enhancer-like chromatin regions. CHD2 depletion causes
      increased histone H3 and reduced histone variant H3.3 occupancy. CONCLUSIONS: We
      conclude that transcription-coupled recruitment of CHD1 and CHD2 occurs at
      transcribed gene TSSs and at intragenic and intergenic enhancer-like sites. The
      recruitment of CHD1 and CHD2 regulates the architecture of active chromatin
      regions through chromatin accessibility and nucleosome disassembly.

PMID- 25621014
TI  - Single cell genomics of bacterial pathogens: outlook for infectious disease
      research.
AB  - Genomic sequencing from single cells is a powerful tool in microbiology and holds
      great promise for infectious disease research. Vast numbers of uncultivable
      species and pathogens that persist at low abundance in environmental reservoirs
      are now accessible for genomic analysis. 

PMID- 25621015
TI  - Molecular breast imaging: an emerging modality for breast cancer screening.
AB  - Screening mammography is recognized as an imperfect imaging tool that performs
      poorly in women with dense breast tissue - a limitation which has driven demand
      for supplemental screening techniques. One potential supplemental technique is
      molecular breast imaging (MBI). Significant improvements in gamma camera
      technology allow MBI to be performed at low radiation doses, comparable with
      those of tomosynthesis and mammography. A recent screening trial in women with
      dense breast tissue yielded a cancer detection rate of 3.2 per 1000 for
      mammography alone and 12.0 per 1000 for the combination of mammography and MBI.
      MBI also demonstrated a lower recall rate than that of mammography. MBI is a
      promising supplemental screening technique in women with dense breast tissue.

PMID- 25621016
TI  - Expression of one important chaperone protein, heat shock protein 27, in
      neurodegenerative diseases.
AB  - INTRODUCTION: Many neurodegenerative diseases are characterised by accumulations
      of misfolded proteins that can colocalise with chaperone proteins (for example,
      heat shock protein 27 (HSP27)), which might act as modulators of protein
      aggregation. METHODS: The role of HSP27 in the pathogenesis of neurodegenerative
      disorders such as frontotemporal lobar degeneration (FTLD), Alzheimer's disease
      (AD) and motor neuron disease (MND) was investigated. We used immunohistochemical
      and Western blot analysis to determine the distribution and amount of this
      protein in the frontal and temporal cortices of diseased and control subjects.
      RESULTS: HSP27 immunostaining presented as accumulations of granules within
      neuronal and glial cell perikarya. Patients with AD and FTLD were affected more
      often, and showed greater immunostaining for HSP27, than patients with MND and
      controls. In FTLD, there was no association between HSP27 and histological type.
      The neuropathological changes of FTLD, AD and MND were not immunoreactive to
      HSP27. Western blot analysis revealed higher HSP27 expression in FTLD than in
      controls, but without qualitative differences in banding patterns. CONCLUSIONS:
      The pattern of HSP27 immunostaining observed may reflect the extent of ongoing
      neurodegeneration in affected brain areas and is not specific to FTLD, AD or MND.
      It may represent an accumulation of misfolded, damaged or unwanted proteins,
      awaiting or undergoing degradation.

PMID- 25621017
TI  - Eyes-closed task-free electroencephalography in clinical trials for Alzheimer's
      disease: an emerging method based upon brain dynamics.
AB  - Electroencephalography (EEG) is a longstanding technique to measure electrical
      brain activity and thereby an indirect measure of synaptic activity. Synaptic
      dysfunction accompanies Alzheimer's disease (AD) and EEG can be regarded as a
      potentially useful biomarker in this disease. Lately, emerging analysis
      techniques of time series have become available for EEG, such as functional
      connectivity and network analysis, which have increased the possibilities for use
      in AD clinical trials. In this review, we report the EEG changes in the course of
      AD, including slowing of the EEG oscillations, decreased functional connectivity
      in the higher-frequency bands, and decline in optimal functional network
      organization. We discuss the use of EEG in clinical trials and provide directions
      for future research. 

PMID- 25621018
TI  - Imaging endpoints for clinical trials in Alzheimer's disease.
AB  - As the need to develop a successful disease-modifying treatment for Alzheimer's
      disease (AD) becomes more urgent, imaging is increasingly used in therapeutic
      trials. We provide an overview of how the different imaging modalities are used
      in AD studies and the current regulatory guidelines for their use in clinical
      trials as endpoints. We review the current literature for results of imaging
      endpoints of efficacy and safety in published clinical trials. We start with
      trials in mild to moderate AD, where imaging (largely magnetic resonance imaging
      (MRI)) has long played a role in inclusion and exclusion criteria; more recently,
      MRI has been used to identify adverse events and to measure rates of brain
      atrophy. The advent of amyloid imaging using positron emission tomography has led
      to trials incorporating amyloid measurements as endpoints and incidentally to the
      recognition of the high proportion of amyloid-negative individuals that may be
      recruited into these trials. Ongoing and planned trials now commonly include
      multimodality imaging: amyloid positron emission tomography, MRI and other
      modalities. At the same time, the failure of recent large profile trials in mild
      to moderate AD together with the realisation that there is a long prodromal
      period to AD has driven a push to move studies to earlier in the disease. Imaging
      has particularly important roles, alongside other biomarkers, in assessing
      efficacy because conventional clinical outcomes may have limited ability to
      detect treatment effects in these early stages. 

PMID- 25621020
TI  - Determination of Methylarginines in Infant Plasma by CE-LIF.
AB  - Methylarginines (MAs) are a class of nitric oxide synthase inhibitors that have
      been implicated in respiratory complications of critically ill infants. This
      paper describes the development of an analytical method to measure these
      compounds in the plasma of newborns using capillary electrophoresis (CE). The CE
      separation method was optimized to enable complete baseline resolution of the
      four MA analogues of interest. Sample preparation concerns for infant-derived
      samples were addressed by validating a heat-assisted extraction method for the
      analysis of low volume (<=100 uL) samples from a plasma matrix. It was determined
      that the sample matrix (plasma versus serum) did not affect the measured MA
      concentrations, while extracting smaller volumes of plasma that underwent heat
      induced gelation afforded higher MA recoveries than larger volume samples. These
      methods were then applied to blood samples collected from infants housed in the
      neonatal intensive care unit. It was discovered that these newborns had
      significantly elevated concentrations of MAs at younger ages (< 6 months) while
      amounts were similar between infants 6 months old and adults. The data are
      preliminary, but demonstrate an interesting age dependence on the concentrations
      of these nitric oxide inhibitors, which has not been previously reported.

PMID- 25621019
TI  - BACE1 inhibitor drugs in clinical trials for Alzheimer's disease.
AB  - beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the beta
      secretase enzyme required for the production of the neurotoxic beta-amyloid
      (Abeta) peptide that is widely considered to have a crucial early role in the
      etiology of Alzheimer's disease (AD). As a result, BACE1 has emerged as a prime
      drug target for reducing the levels of Abeta in the AD brain, and the development
      of BACE1 inhibitors as therapeutic agents is being vigorously pursued. It has
      proven difficult for the pharmaceutical industry to design BACE1 inhibitor drugs
      that pass the blood-brain barrier, however this challenge has recently been met
      and BACE1 inhibitors are now in human clinical trials to test for safety and
      efficacy in AD patients and individuals with pre-symptomatic AD. Initial results
      suggest that some of these BACE1 inhibitor drugs are well tolerated, although
      others have dropped out because of toxicity and it is still too early to know
      whether any will be effective for the prevention or treatment of AD.
      Additionally, based on newly identified BACE1 substrates and phenotypes of mice
      that lack BACE1, concerns have emerged about potential mechanism-based side
      effects of BACE1 inhibitor drugs with chronic administration. It is hoped that a
      therapeutic window can be achieved that balances safety and efficacy. This review
      summarizes the current state of progress in the development of BACE1 inhibitor
      drugs and the evaluation of their therapeutic potential for AD. 

PMID- 25621021
TI  - Positron emission tomography/computed tomography for bone tumors (Review).
AB  - The aim of the present study was to investigate positron emission tomography
      (PET)/computed tomography (CT) and its applications for the diagnosis and
      treatment of bone tumors. The advantages and disadvantages of PET/CT were also
      evaluated and compared with other imaging methods and the prospects of PET/CT
      were discussed. The PubMed, Medline, Elsevier, Wanfang and China International
      Knowledge Infrastructure databases were searched for studies published between
      1995 and 2013, using the terms 'PET/CT', 'positron emission tomography', 'bone
      tumor', 'osteosarcoma', 'giant cell bone tumor' and 'Ewing sarcoma'. All the
      relevant information was extracted and analyzed. A total of 73 studies were
      selected for the final analysis. The extracted information indicated that at
      present, PET/CT is the imaging method that exhibits the highest sensitivity,
      specificity and accuracy. Although difficulties and problems remain to be solved,
      PET/CT is a promising non-invasive method for the diagnostic evaluation of and
      clinical guidance for bone tumors.

PMID- 25621022
TI  - Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia.
AB  - Cytokine-induced killer (CIK) cells are NK-like T cells derived from peripheral
      blood mononuclear cells that are co-stimulated and expanded using cytokines for
      14-21 days in vitro. CIK cells are a heterogeneous subset of highly-efficient
      cytotoxic T effector cells that mediate major histocompatibility complex
      unrestricted cytotoxicity against a broad array of tumor cells. These effector
      cells are generated from patients with leukemia or healthy donors who demonstrate
      similar cytotoxic activity against leukemia blasts. Allogeneic CIK cells retain
      the ability to produce the graft versus tumor response and generate minimal graft
      versus host disease. In addition, CIK cells possess no cytotoxicity against
      normal hematopoietic stem cells in vivo. Leukemia recurrence remains a formidable
      obstacle, but adoptive immunotherapy offers promise for the eradication of
      minimal residual disease and prevention of leukemia relapse following
      hematopoietic stem cell transplantation. CIK cell infusion started a novel
      generation of adoptive immunotherapy and exhibits particular potential
      applications in the area of hematological malignancy. In the present study, the
      previous strategies of leukemia immunotherapy using CIK cells are reviewed and
      the future directions of development are discussed.

PMID- 25621023
TI  - Subcellular location and photodynamic therapeutic effect of chlorin e6 in the
      human tongue squamous cell cancer Tca8113 cell line.
AB  - The present study aimed to investigate the distribution and photodynamic
      therapeutic effect of chlorin e6 (Ce6) in the human tongue squamous cell
      carcinoma Tca8113 cell line in vitro. The distribution of Ce6 in the Tca8113
      cells was observed in situ combined with mitochondrial and lysosomal fluorescent
      probes. Next, 630-nm semiconductor laser irradiation was performed. The MTS
      colorimetric method was used to determine cell survival. Annexin V fluorescein
      isothiocyanate/propidium iodide (PI) double staining was used to detect early
      apoptosis following photodynamic therapy (PDT). The flow cytometer was used to
      analyze the DNA content subsequent to PI-staining. It was observed that Ce6 could
      combine with the cellular membrane following 30 min of incubation with the
      Tca8113 cells. As the length of incubation increased, Ce6 gradually entered the
      cells in a particular distribution and reached saturation by 3 h. Co-localization
      analysis demonstrated that Ce6 was more likely to be present in the mitochondria
      than in the lysosomes. The cells incubated with 5 MUg/ml Ce6 for 24 h exhibited a
      low toxicity of 5%, however, following light irradiation, Ce6-PDT was able to
      kill the Tca8113 cells in vitro. The cell toxicity was positively correlated with
      Ce6 concentration and light dose, therefore, the effect of Ce6 was
      concentration/dose-dependent (P<0.01). The lower Ce6 concentrations and light
      doses could significantly induce apoptosis in the Tca8113 cells, while higher
      doses increased necrosis/percentage of dead cells. In summary, Ce6 saturated the
      Tca8113 cells following 3 h of incubation. Furthermore, Ce6-PDT effectively
      killed the cultured Tca8113 cells in vitro at a safe concentration. At a low
      concentration and light dose, Ce6 is more likely to induce cell apoptosis via the
      mitochondria than the lysosomes.

PMID- 25621024
TI  - Clinical investigation into the initial diagnosis and treatment of 1,168 lung
      cancer patients.
AB  - The aim of the present study was to analyse clinical data obtained from lung
      cancer patients, including the initial clinical symptoms upon diagnosis, duration
      of patient delay in presenting to a doctor, lung cancer stage, treatment strategy
      and prognosis. A retrospective analysis was conducted of the clinical features of
      1,168 lung cancer patients who were initially diagnosed and treated at the Tumor
      Hospital of Shandong Province (Jinan, China) in 2009. The Kaplan-Meier method and
      multivariate Cox regression analysis were performed to analyse the influence of
      gender, age, predominant symptoms, histopathological or cytological type and
      clinical staging on the overall patient survival. The follow-up rate of the
      present study was 92.4%, and the 1-, 2- and 3-year survival rates were 80.4, 44.9
      and 15.8%, respectively. Multivariate analysis demonstrated that the patient age,
      extent of the tumour (T stage), extent of lymph node spread (N stage), overall
      clinical stage and treatment strategy were independent risk factors associated
      with patient survival. The present study identified that the initial symptoms of
      lung cancer varied, patient delay was long, the lung cancer cases were diagnosed
      in late clinical stages and the prognosis was poor.

PMID- 25621025
TI  - TP53-induced glycolysis and apoptosis regulator promotes proliferation and
      invasiveness of nasopharyngeal carcinoma cells.
AB  - The TP53-induced glycolysis and apoptosis regulator (TIGAR) is the protein
      product of the p53 target gene, C12orf5. TIGAR blocks glycolysis and promotes
      cellular metabolism via the pentose phosphate pathway; it promotes the production
      of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to
      enhanced scavenging of intracellular reactive oxygen species, and inhibition of
      oxidative stress-induced apoptosis in normal cells. Our previous study identified
      a novel nucleoside analog that inhibited cellular growth and induced apoptosis in
      nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression.
      Furthermore, the growth inhibitory effects of c-Met tyrosine kinase inhibitors
      were ameliorated by the overexpression of TIGAR in the NPC cell lines. These
      results indicate a significant role for TIGAR expression in the survival of NPCs.
      The present study aimed to further define the function of TIGAR expression in NPC
      cells. In total, 36 formalin-fixed, paraffin-embedded NPC tissue samples were
      obtained for the immunohistochemical determination of TIGAR expression. The
      effects of TIGAR expression on cell proliferation, NADPH production and cellular
      invasiveness were also assessed in NPC cell lines. Overall, TIGAR was
      overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent non
      cancer epithelial cells. Similarly, TIGAR overexpression was also observed in a
      panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell
      lines. TIGAR overexpression led to increased cellular growth, NADPH production
      and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression
      resulted in significant inhibition of cellular growth and invasiveness. The
      expression of the two mesenchymal markers, fibronectin and vimentin, was
      increased by TIGAR overexpression, but reduced following TIGAR-knockdown. The
      present study revealed that TIGAR overexpression led to increased cellular
      growth, NADPH production and invasiveness, and the maintenance of a mesenchymal
      phenotype, in NPC tissues.

PMID- 25621026
TI  - Follicular dendritic cell sarcoma of the right tonsil: A case report and
      literature review.
AB  - The current study presents a case of extranodal follicular dendritic cell sarcoma
      (FDCS) of the tonsil and reviews the relevant literature. In the present case, a
      59-year-old male presented with a globus sensation in the right pharynx for 6
      weeks. On clinical examination, a painless non-ulcerated enlarged right tonsil
      was identified; the tonsil was covered with a normal mucus membrane. A right
      tonsillectomy was performed under general anesthesia. The final pathological
      diagnosis was follicular dendritic cell sarcoma of the right tonsil.
      Postoperatively, the patient received radiotherapy. The patient remains alive
      without disease recurrence or metastasis 44 months after tonsillectomy. To the
      best of our knowledge, only 42 cases of FDCS of the tonsil have been reported to
      date. Of the 42 cases, 41 patients underwent surgery and one patient refused
      treatment. A total of 23 (54.7%) received surgery alone. Adjuvant treatment was
      administered for 18 patients (42.9%). Six patients (14.3%) experienced local
      recurrences and two patients (4.8%) succumbed to the disease 24 months after
      treatment. The three-, five-, and eight-year overall survival rates for the
      entire group were 86.5, 77.8 and 77.8%, respectively. Furthermore, a tumor
      diameter of >=4 cm was prognostic upon univariate analysis (chi2=4.634; P=0.031;
      excluding incomplete data). Tonsillar FDCS is rare and is associated with high
      rates of recurrence and metastasis, therefore, adjuvant treatment should be
      prescribed.

PMID- 25621027
TI  - Intramuscular dendritic fibromyxolipoma in a 24-year-old male: A case report and
      review of the literature.
AB  - Dendritic fibromyxolipoma (DFML) is an uncommon, benign soft tumor that usually
      arises in the subcutis. To date, ~24 cases of DFML have been reported in the
      literature and only one of these has been in the muscle. The present study
      reports the case of a 24-year-old male with a slow-growing, painless mass located
      deep in the triceps brachii in the left shoulder region. The mass was
      14.0*8.5*8.0 cm in size, with well-circumscribed margins. Microscopically, the
      resected mass was characterized by a proliferation of small spindle or stellate
      cells, prominent abundant myxoid stroma with ropey collagen bundles and admixed
      mature adipose tissue. Further immunohistochemical staining indicated that the
      spindle and stellate cells were reactive with cluster of differentiation 34,
      vimentin and B-cell lymphoma-2, but not with smooth muscle actin and desmin.
      Fluorescence in situ hybridization showed that the tumor cells did not have the
      DDIT3 alteration or amplification of MDM2. The tumor was confirmed to be a DFML
      due to the typical histological, immunophenotypic and genetic findings. To date,
      subsequent to 4 years of clinical follow-up, there is no sign of recurrence or
      metastasis. The present study reports a case of DFML in the youngest known
      patient, and is the second reported case of an intramuscular DFML occurring in
      the triceps brachii in the left shoulder region. The study discusses the
      clinicopathological features and the differential diagnosis of DFML, with a
      review of the literature.

PMID- 25621028
TI  - Research of shRNAmir inhibitory effects towards focal adhesion kinase expression
      in the treatment of gastric cancer.
AB  - Gastric cancer is the fourth most common type of malignant tumor, with a poor
      prognosis. Focal adhesion kinase (FAK) mediates the crosslink of intracellular
      signaling networks, playing a key role in cell migration and invasion. The aim of
      the present study was to investigate the effects of FAK interference on the
      proliferation ability, invasion and metastasis of gastric cancer cells. The FAK
      RNAi lentiviral vector was infected into SGC7901 gastric cancer cells in order to
      observe the in vivo situations of tumor growth and metastasis before and after
      the FAK interference. The growth of SGC7901 gastric cancer cells in the
      interference group was significantly inhibited compared with that of the negative
      control (P<0.05) and the blank control groups (P<0.05), and the FAK expression
      significantly decreased (P<0.05). The in vitro invasion and metastasis
      experiments showed that the cell invasion and metastasis abilities of the
      interference group significantly decreased when compared with those of the
      negative control (P<0.05) and blank control groups (P<0.05). In the nude mouse
      subcutaneous tumor transplantation model, the mean +/- standard deviation tumor
      weight of the interference group (1.474+/-0.9840 g) was lower than that of the
      negative control (3.134+/-0.3299 g) and blank control (2.68+/-0.12 g) groups
      (P<0.05). In the nude mice, the liver and peritoneal metastasis rates of the
      interference group were significantly lower than those of the negative control
      (P<0.05) and the blank control groups (P<0.05), and the FAK mRNA of the
      interference group significantly reduced (P<0.05). In conclusion, FAK
      interference could effectively suppress the proliferation, invasion and
      metastasis of transfected SGC7901 gastric cancer cells, and could inhibit the
      growth and distant metastasis of gastric cancer in nude mice.

PMID- 25621029
TI  - A novel mutation of thyroid hormone receptor beta in exon 10 in a case of thyroid
      hormone-resistant non-Hodgkin's lymphoma of the thyroid.
AB  - Only a few previous studies have demonstrated an association between resistance
      to thyroid hormone (RTH) and thyroid cancer. The current study presents the case
      of a 67-year-old female who was referred to the Third Xiangya Hospital of Central
      South University with an enlargement of the neck that had grown gradually over
      two years and subsequently, rapidly enlarged over the two months prior to
      admission, alongside a slight sensation of shortness of breath. Laboratory data
      revealed a significantly increased level of thyroid-stimulating hormone (TSH),
      total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine,
      thyroprotein and thyroglobulin antibody; however, the levels of thyroperoxidase
      and TSH receptor antibody were within the normal ranges. A thyroid hormone
      suppression test revealed a TSH reduction of 32%, Magnetic resonance imaging of
      the pituitary gland was negative for abnormalities. The patient's thyroid
      pathology revealed a non-Hodgkin's lymphoma of the thyroid. CHOP + nimustine
      chemotherapy significantly reduced the clinical symptoms. The genetic analysis
      revealed a novel point mutation of the thyroid hormone receptor beta (THRB) gene
      in exon 10 (g1680 G to A) in the 3'-untranslated region of the patient. To the
      best of our knowledge, this is the first case report of RTH with thyroid non
      Hodgkin's lymphoma, which involved a mutation (g1680 G to A) in exon 10 of THRB.

PMID- 25621030
TI  - Extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of the mediastinum:
      Significant response to chemoradiotherapy.
AB  - Primary mediastinal extraskeletal Ewing's sarcoma (EES) is quite rare. To the
      best of our knowledge, only five cases have been reported. Given the paucity of
      data, there is consequently no optimal treatment strategy available. The current
      study presents the case of a 51-year-old female with unresectable EES of the
      posterior mediastinum. Chemoradiotherapy achieved near complete remission without
      severe side-effects. The literature associated with EES is also reviewed. The
      present case highlights the possibility of the diagnosis of EES for a mediastinal
      mass. Chemoradiotherapy may be a good option for unresectable cases. In the
      future, large-scale collaborative clinical trials should be initiated to provide
      an improved understanding of the characteristics of EES and the best treatment
      strategy.

PMID- 25621031
TI  - Shikonin induces apoptosis and inhibits migration of ovarian carcinoma cells by
      inhibiting the phosphorylation of Src and FAK.
AB  - The present study identified that shikonin, a naphthoquinone extracted from the
      roots of Lithospermum erythrorhizon, inhibits the migration of ovarian cancer
      cells and induces their apoptosis by impairing the phosphorylation of two
      kinases, proto-oncogene tyrosine protein kinase Src (Src) and focal adhesion
      kinase (FAK). Ovarian carcinoma SKOV-3 cells were treated with various
      concentrations of shikonin and analyzed for the effects on cell migration,
      invasion and apoptosis via Transwell assays and flow cytometry. In addition, the
      effects of shikonin administration on the expression and phosphorylation of Src
      and FAK in the SKOV-3 cells were analyzed by western blotting. Shikonin appeared
      to induce apoptosis and decrease cell migration in the SKOV-3 ovarian cells.
      Furthermore, the present study provides evidence that shikonin may exert these
      effects on human ovarian carcinoma cells via the inhibition of the protein
      tyrosine kinases, Src and FAK. Thus, shikonin should be considered for additional
      investigation as a candidate agent for the prevention and treatment of human
      ovarian cancer.

PMID- 25621032
TI  - microRNA-214 functions as a tumor suppressor in human colon cancer via the
      suppression of ADP-ribosylation factor-like protein 2.
AB  - microRNAs (miRNAs/miRs) are a conserved class of endogenous, short non-coding
      RNAs that post-transcriptionally regulate the expression of genes involved in
      diverse cellular processes. miR-214 has been reported to be associated with
      several cancers, including human colon cancer. However, the function of miR-214
      in colon cancer development is poorly understood. In the current study, miR-214
      was demonstrated to be downregulated in colon cancer tissues compared with
      healthy colon tissues. Functional studies showed that miR-214 overexpression
      results in the inhibition of cell viability, colony formation and proliferation,
      and the induction of cell apoptosis. ADP-ribosylation factor-like protein 2
      (ARL2) is predicted to be a target candidate of miR-214. A luciferase reporter
      assay, western blot analysis and quantitative polymerase chain reaction were
      performed, which revealed that miR-214 negatively regulates ARL2 expression by
      targeting its 3' untranslated region directly. In conclusion, the results of the
      present study revealed that miR-214 suppresses colon cancer cell growth via the
      suppression of ARL2, and indicated that miR-214 may present a significant
      potential therapeutic target for colon cancer.

PMID- 25621033
TI  - Predictive value of vascular endothelial growth factor polymorphisms on the
      clinical outcome of renal cell carcinoma patients.
AB  - A cohort study was conducted to investigate the association between vascular
      endothelial growth factor (VEGF) polymorphisms -2578C/A, -1154G/A and -634C/G and
      the clinical outcome of renal cell carcinoma (RCC), as well as the interaction of
      VEGF polymorphisms with tumor stage, metastasis and size. A total of 310 RCC
      patients were recruited from the First Affiliated Hospital of Zhengzhou
      University (Zhengzhou, China) between January 2006 and December 2007, and were
      followed up until December 2012. The association between the three single
      nucleotide polymorphisms and the overall survival of RCC patients was estimated
      using Cox's proportional hazard regression model. The median follow-up duration
      was 34.7 months and 74 of the RCC patients succumbed due to cancer during the
      follow-up period. The frequency of the VEGF -2578 AA genotype was significantly
      higher in patients classed as tumor stages III-IV (odds ratio [OR], 0.47; 95%
      confidence interval [CI], 0.24-0.95) and larger tumors (longest diameter, >4 cm;
      OR, 0.44; 95% CI, 0.22-0.89). Furthermore, the frequency of VEGF -634 GG was
      significantly higher in patients with larger tumors (longest diameter, >4 cm; OR,
      0.68; 95% CI, 0.48-0.97). The VEGF -2578 AA genotype was correlated with a 2.96
      fold increase in the risk of RCC-associated mortality and was associated with a
      five-year survival rate of ~25%. Therefore, the present study identified that the
      VEGF -2578C/A polymorphism may be associated with the prognosis of RCC patients,
      and may interact with the tumor stage and size.

PMID- 25621034
TI  - Synovial sarcoma: Magnetic resonance and computed tomography imaging features and
      differential diagnostic considerations.
AB  - The present study retrospectively examined 24 cases of pathologically confirmed
      synovial sarcoma and analyzed the clinical presentation and imaging findings in
      order to explore the imaging features of synovial sarcoma. The majority of the
      lesions were large (>5 cm; 88%), rounded or lobulated, relatively well-defined
      tumor masses in the extremities near the joints or deeply located. On computed
      tomography (CT) scans, the lesions demonstrated intensity signals similar to
      those of muscle. Six cases exhibited punctate calcification in the periphery of
      the tumor. On T1-weighted images, the largest lesions of >5 cm, were usually
      heterogeneous, with a signal intensity similar to or slightly higher than that of
      muscle. On T2-weighted images, heterogeneous high-intensity or slightly high
      intensity signals were observed, with 12 cases exhibiting a high signal
      consistent with hemorrhage and 12 presenting signals that indicated internal
      septations. Contrast-enhanced scanning revealed heterogeneous enhancement in the
      majority of the lesions and no enhancement in areas of cystic necrosis or
      internal septations. Synovial sarcoma has specific imaging features, and
      comprehensive analysis of CT and magnetic resonance imaging can improve the
      accuracy of the pre-operative diagnosis.

PMID- 25621035
TI  - Stromal myofibroblasts in potentially malignant and malignant lesions of the oral
      cavity.
AB  - Previous studies have demonstrated that myofibroblasts in the adjacent stroma are
      involved in the development and progression of malignant tumors. The aim of this
      study was to investigate the involvement of myofibroblasts in the progression of
      oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in
      potentially malignant and malignant oral lesions. A total of 69 potentially
      malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90
      OSCCs (well-, moderately and poorly differentiated), eight oral verrucous
      carcinomas and 29 fibrous hyperplasias were examined for the presence of
      myofibroblasts using immunohistochemical detection of isoform alpha of smooth
      muscle actin. Myofibroblasts were not identified in the adjacent stroma of
      fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the
      oral carcinomas exhibited myofibroblasts in various densities. The density was
      significantly higher in moderately and poorly differentiated OSCCs when compared
      with well-differentiated tumors (P=0.04 and P=0.007, respectively). In verrucous
      carcinomas, the specific variant of well-differentiated OSCC, stromal
      myofibroblasts were not detected. The results of the present study demonstrated
      that immunodetection of myofibroblasts does not aid with the determination of the
      malignant transformation potential of oral dysplasias, although moderately and
      poorly differentiated tumors exhibited a significantly higher density of
      myofibroblasts. The results reinforce the hypothesis that myofibroblasts may
      contribute to oral tumorigenesis, indicating that verification and monitoring of
      such may serve as a putative marker of OSCC behavior.

PMID- 25621036
TI  - Expression and clinical significance of matrix metalloproteinase-17 and -25 in
      gastric cancer.
AB  - The aim of the present study was to investigate the expression and
      clinicopathological features of matrix metalloproteinase 17 (MMP17; also known as
      MT4-MMP) and MMP25 (also known as MT6-MMP) in gastric cancer.
      Immunohistochemistry and reverse transcription-quantitative polymerase chain
      reaction were used to detect the expression of MMP17 and MMP25 in 42 cases of
      gastric carcinoma and normal tissues, and 40 cases of atrophic gastritis. The
      expression of MMP17 in the normal gastric and atrophic gastritis tissues was
      significantly lower than that in the gastric cancer tissues (P<0.05). The
      expression of MMP25 in the gastric cancer and atrophic gastritis tissues was
      markedly higher compared with the normal gastric tissues (P<0.05). The expression
      of MMP17 and MMP25 was significantly associated with the depth of tumor invasion,
      lymph node metastasis and serous membrane involvement (P<0.05), but not with
      patient age and gender, or lesion length, site and histological grade (P>0.05).
      Therefore, this indicates that the expression of MMP17 and MMP25 is increased
      with the degree of progress of gastric carcinoma. The detection of MMP17 and
      MMP25 expression may have clinical value in predicting the prognosis of patients
      with gastric cancer.

PMID- 25621037
TI  - Unusual primary osseous Hodgkin's lymphoma: A case report.
AB  - Hodgkin's lymphoma (HL) is one of the few adult malignancies that most frequently
      presents with a progressive, painless enlargement of the peripheral lymph nodes.
      A primary osseous presentation of HL, without lymph node involvement, is
      extremely rare. The present study describes a case of primary multifocal osseous
      HL in a 22-year-old female. The patient presented with pain in the lumbar-sacral
      pelvic area and a prolonged fever. Pathological examination led to a diagnosis of
      primary multifocal osseous lymphoma, and the patient was subsequently prescribed
      a course of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)
      chemotherapy. Following this, the patient recovered with no pain or fever, and
      computed tomography identified no further progression. The clinical, radiological
      and histological features of HL are similar to those of other medical conditions,
      such as tuberculosis and eosinophilic granuloma. Furthermore, in rare cases, HL
      may even occur in combination with multiple myeloma. This makes it difficult to
      diagnose the condition, which often leads to a delay in treatment. Clinicians
      should not ignore HL when it manifests in the unusual primary osseous form.

PMID- 25621038
TI  - Brain metabolic changes in Hodgkin disease patients following diagnosis and
      during the disease course: An 18F-FDG PET/CT study.
AB  - The aim of the present study was to investigate brain glucose metabolism in
      patients with Hodgkin disease (HD) after diagnosis and during chemotherapy
      treatment. Following the administration of first-line doxorubicin, bleomycin,
      vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18F
      fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed
      tomography brain scans, both baseline (PET0) and interim (PET2) at the Department
      of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy).
      Fifty-seven patients were further evaluated 15+/-6 days after four additional
      cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naive
      subjects was enrolled. Differences in brain 18F-FDG uptake between the CG, PET0,
      PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared
      with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic
      activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally
      and in left BA 32. All of these changes disappeared at PET6. The results of the
      present study indicate that ABVD chemotherapy has a limited impact on brain
      metabolism.

PMID- 25621039
TI  - Herbal medicine Guan Chang Fu Fang enhances 5-fluorouracil cytotoxicity and
      affects drug-associated genes in human colorectal carcinoma cells.
AB  - Guan Chang Fu Fang (GCFF) is a natural compound, which is extracted from three
      medicinal plants, Agrimonia pilosa Ledeb., Patrinia scabiosaefolia and Solanum
      nigrum L. GCFF has demonstrated clinical efficacy in the treatment of colon
      cancer. At present, 5-fluorouracil (5-FU) is the primary active chemotherapeutic
      agent used for treating colon cancer. Using median-effect and apoptosis analyses,
      fluorescence microscopy and western blotting, the present study analyzed the
      association between GCFF and 5-FU in the human colon adenocarcinoma LoVo cell
      line. The effect of GCFF on the expression of chemotherapeutic agent-associated
      genes was also investigated. The results of the synergistic analysis revealed
      that GCFF exhibited a significant effect upon 5-FU-associated cytotoxicity within
      the LoVo cell line. This effect was observed over a broad dose-inhibition range
      (5-95%), but was particularly significant in the lower concentrations. The flow
      cytometry results revealed that low doses of GCFF or 5-FU induced S-phase arrest,
      as did a low-dose combination of the two drugs. After 48 h, GCFF significantly
      suppressed the expression levels of the chemotherapeutic agent resistance
      associated genes within the colon cancer cells. The western blot analysis
      revealed that the combined effects of 5-FU and GCFF were due to a regulation of
      the B-cell lymphoma-2 family of proteins. The findings of the present study
      suggested that GCFF, when combined with 5-FU, has the potential to be a novel,
      chemotherapeutic compound for the treatment of colon cancer.

PMID- 25621040
TI  - Increased BRAF copy number in lung adenocarcinoma.
AB  - Point mutation of the BRAF gene is a genetic event that occurs in a subset of
      lung adenocarcinoma cases. For example, BRAF V600E is a driver mutation that can
      be effectively targeted using selective BRAF and/or MEK inhibitors. The present
      study hypothesized that an increase in BRAF copy number may be correlated with
      certain clinicopathological features of lung adenocarcinoma in Japanese patients.
      The BRAF gene copy number was analyzed using quantitative polymerase chain
      reaction amplifications in 29 surgically treated lung adenocarcinoma cases
      without EGFR or Kras mutations from Nagoya City University Hospital (Nagoya,
      Japan). Seven BRAF-mutant cases were included. Increased BRAF gene copy number
      was identified in three lung adenocarcinoma patients (10.3%), all of which
      exhibited the V600E mutation. Using fluorescence in situ hybridization with BRAF
      specific and chromosome 7 centromeric probes, increased copy number status was
      associated with gene amplification or gain of chromosome 7. Although increased
      BRAF copy number was correlated with BRAF V600E mutations, numerical changes in
      BRAF copy number were rare and mild in lung adenocarcinoma, resulting in no
      significant difference in pathological tumor status or tumor stage.

PMID- 25621041
TI  - Endoscopic transsphenoidal resection of sellar tumors with conchal sphenoid
      sinus: A report of two cases.
AB  - A conchal non-pneumatized sphenoid sinus was previously considered to be a
      contraindication to the endoscopic transsphenoidal route to the sella due to its
      small sellar floor and poor anatomical landmarks, such as the optic nerve canal,
      opticocarotid recess and internal carotid arteries canal. The present study aimed
      to investigate the methodology and characteristics of the endoscopic
      transsphenoidal resection of sellar tumors with a conchal sphenoid sinus. Two
      patients with sellar tumor patients and non-pneumatized sphenoid sinuses received
      endoscopic transsphenoidal surgery. The two conchal sphenoid sinuses were
      accessed safely, total resection was achieved and no serious complications
      occurred. Therefore, the presence of a conchal non-pneumatized sphenoid is not an
      absolute contraindication for employing the endoscopic transsphenoidal route in
      the resection of sellar tumors; a positive outcome may be achieved, in particular
      when the surgery is performed by an experienced otolaryngologist.

PMID- 25621042
TI  - Leiomyomatosis peritonealis disseminata associated with endometriosis: A case
      report and review of the literature.
AB  - Leiomyomatosis peritonealis disseminata (LPD) is a specific type of
      leiomyomatosis with an unclear pathogenesis that is rarely diagnosed by clinical
      evaluation. To date, <200 cases have been reported. The majority of the patients
      have a medical history of laparoscopic myomectomy for uterine fibroids. The use
      of laparoscopic power morcellation may be a contributor to the development of
      LPD, therefore, the specific surgical approach used in laparoscopic myomectomy
      should be carefully considered, and protective measures should be taken to
      prevent myoma fragments spreading if laparoscopic power morcellation is used. The
      present study reviewed and analyzed the medical history, diagnostic process and
      treatment strategy of a case of LPD to improve our understanding of the disease.
      In this report, the case of a 34 year-old female who underwent laparoscopic
      myomectomy to remove a uterine fibroid is presented. During the surgery, a myoma
      was resected using morcellators. Three years after surgery, exploratory
      laparotomy was performed due to uterine fibroid recurrence. During surgery, myoma
      was identified at the uterine bladder peritoneal reflection, where several
      unequally sized leiomyoma tubercles were identified on the uterine surface.
      Subsequently, myomectomy was performed. Postoperative pathology diagnosed
      leiomyoma. Two years later, gynecological ultrasound revealed a mass in the
      abdomen. Exploratory laparotomy was subsequently performed. During surgery,
      compact myoma tubercle-like cysts were identified on the surface of the intestine
      and mesentery, and an endometriotic cyst was identified on the left ovary. As the
      myomas were too compact to remove completely, the majority of leiomyoma on the
      intestine and mesentery was resected. The endometriotic cyst on the left ovary
      was also resected. Considering the patient's medical history, observations during
      surgery and pathological results, the final diagnosis was LPD. Following surgery,
      the patient was treated with the gonadotropin-releasing hormone agonist,
      triptorelin acetate (3.5 mg, once every four weeks), for three months and
      followed-up every six months. In October 2014, a gynecological sonography
      examination revealed no abnormalities and at the time of writing, the patient
      remains alive and well.

PMID- 25621043
TI  - Unusual synchronous skeletal muscle and lung metastasis in papillary thyroid
      cancer: A case report and review of the literature.
AB  - Papillary thyroid cancer (PTC) frequently metastasizes to the cervical lymph
      region and less often to the lung and bone. Metastasis to the skeletal muscles
      from PTC is extremely rare, especially concurrent lung and skeletal muscle
      metastases. The present study reports the case of a 31-year-old man with
      synchronous metastasis to the skeletal muscle and lung from PTC, six years
      following total thyroidectomy and consecutive 131Iodine treatments. Magnetic
      resonance imaging (MRI) revealed a 1.7*1.2*1.5 cm mass in the left gastrocnemius
      muscle, indicating a neurogenic tumor. The mass was subsequently resected and
      confirmed via histopathology to be metastatic PTC. We propose that, in the follow
      up of patients with PTC, the measurable serum thyroglobulin level, whole body
      scan and other imaging modalities including MRI or positron emission
      tomography/computed tomography, must be closely monitored for potential distant
      metastases, particularly in cases of PTC with aggressive pathological behavior.

PMID- 25621044
TI  - 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the
      inhibition of glycolysis.
AB  - Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore,
      the inhibition of glycolysis may inhibit tumor growth. Our previous study
      demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell
      proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth
      in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the
      present study was to investigate the inhibitory effect of 3-BrPA in an animal
      model of gastric cancer. It was identified that 3-BrPA exhibited strong
      inhibitory effects upon xenograft tumor growth in nude mice. In addition, the
      antitumor function of 3-BrPA exhibited a dose-effect association, which was
      similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3
      BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The
      present study hypothesized that the inhibitory effect of 3-BrPA is achieved
      through the inhibition of hexokinase activity, which leads to the downregulation
      of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X
      protein expression and the subsequent activation of caspase-3. These data suggest
      that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

PMID- 25621045
TI  - An MPL W515L mutation in refractory anemia with ringed sideroblasts associated
      with marked thrombocytosis: A case report.
AB  - The current study presents the case of a 63-year-old patient exhibiting
      refractory anemia with ringed sideroblasts associated with marked thrombocytosis
      (RARS-T), who was positive for the MPL W515L mutation, but negative for the JAK2
      V617F mutation. Following diagnosis, the patient remained asymptomatic for over
      three years, however, in August 2012, the patient relapsed and was administered
      with supportive treatment in the form of subcutaneous darbepoetin alpha at a dose
      of 300 MUg/week, which resulted in an increased hemoglobin concentration,
      allowing the patient to remain transfusion-independent. The MPL W515L mutation
      has been reported in two previous cases of myelodysplastic/myeloproliferative
      neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our
      knowledge, the current report is the first to present a case of RARS-T with an
      MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a
      targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim
      of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL
      is located upstream of the JAK-STAT signaling pathway, it is a possible
      therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but
      negative for a JAK2 V617F mutation.

PMID- 25621046
TI  - Preliminary experience of performing a video endoscopic inguinal lymphadenectomy
      using a hypogastric subcutaneous approach in patients with vulvar cancer.
AB  - To evaluate the feasibility and surgical outcome of video endoscopic inguinal
      lymphadenectomy (VEIL) using a hypogastric subcutaneous approach, 21 patients
      with vulvar cancer who underwent this procedure were included in the present
      study. Between December 2010 and March 2013, 21 consecutive patients with vulvar
      cancer underwent radical vulvectomy and VEIL using a hypogastric subcutaneous
      approach. The intraoperative and post-operative results and follow-up data were
      retrospectively analyzed. No intraoperative complications occurred. The mean
      duration of surgery for the endoscopic inguinal lymphadenectomies was 130 min
      (range, 80-180 min), with a mean estimated blood loss of 103 ml (range, 30-350
      ml). The mean lymph node yield was 15 (range, 10-22 lymph nodes). The suction
      drains were removed after a mean duration of 7 days (range, 5-11 days). No skin
      related complications were observed in the groin region and a lymphocele was only
      observed in 1/21 (4.8%) patients. After a mean follow-up period of 17 months
      (range, 3-31 months), recurrence was found in only one patient. All the patients
      were alive at the time of publication. Based on our preliminary experience,
      performing VEIL using a hypogastric subcutaneous approach is a safe and feasible
      technique for patients with vulvar cancer. These results indicate that this
      surgical technique may decrease the post-operative morbidity of lymphadenectomy
      without compromising the therapeutic efficacy. Future prospective studies with a
      greater sample size and a longer duration of follow-up are required.

PMID- 25621047
TI  - JF-305, a pancreatic cancer cell line is highly sensitive to the PARP inhibitor
      olaparib.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick sensor involved in the base
      excision repair (BER) pathway. Olaparib, a PARP inhibitor, has demonstrated
      antitumor activity in homologous recombination (HR)-deficient cancers. To extend
      this specific therapy to other types of carcinomas, a panel of 11 different
      cancer cells were screened in the present study. JF-305, a pancreatic cancer cell
      line of Chinese origin, demonstrated sensitivity to the PARP inhibitor 6(5H)
      phenanthridinone. In the present study, 3 MUM olaparib conferred a cell survival
      rate of 25% following four days of treatment. The colony formation efficiency was
      83% at 10 nM, and dropped to 12% at 1 MUM following seven days of treatment.
      Furthermore, olaparib induced cell cycle arrest in the S and G2/M phases prior to
      the initiation of apoptosis. Although the incidence of double-strand breaks
      (DSBs) was increased in the olaparib-treated JF-305 cells, the RAD51 foci were
      well formed at the sites of gamma-H2AX recruitment, indicating an activated HR
      mechanism. Furthermore, tumor growth was reduced by 49.8% following 22 days of
      consecutive administration of 10 mg/kg olaparib in the JF-305 xenograft mouse
      model. In summary, the JF-305 cell line was sensitive to olaparib and provided a
      prospective model for the preclinical assessment of PARP inhibitors in the
      therapy of pancreatic cancer.

PMID- 25621048
TI  - Correlation between bone metastasis and thrombocytosis in pulmonary
      adenocarcinoma patients.
AB  - Thrombocytosis is commonly observed in patients exhibiting a variety of
      malignancies, including pulmonary, gastrointestinal and hepatic cancer. In the
      present study, the correlation between distant metastasis and thrombocytosis was
      retrospectively reviewed in 308 cases of histopathologically confirmed pulmonary
      adenocarcinoma. The patients were classified as having thrombocytosis or not,
      based on their platelet counts upon diagnosis; thrombocytosis was documented in
      82/308 patients (26.6%). A log-rank test indicated a statistically significant
      difference in survival between patients exhibiting thrombocytosis compared with
      patients not exhibiting thrombocytosis (P<0.001). In addition, the occurrence of
      distant metastasis and the survival period were correlated with the presence of
      thrombocytosis upon diagnosis. In descending order of frequency, metastases were
      documented at the following sites: Lymph nodes (218/308 patients; 70.8%), bone
      (138/308 patients; 44.8%), lung (93/308 patients; 30.2%), brain (67/308 patients;
      21.8%), liver (46/308 patients; 4.9%), adrenal glands (11/308 patients; 3.6%) and
      kidneys (5/308 patients; 1.6%). Bone metastasis occurred significantly more
      frequently in patients exhibiting thrombocytosis (50/82 patients: 61.0%; P<0.05)
      compared with patients not exhibiting thrombocytosis (88/226 patients; 38.9%).
      Furthermore, according to univariate analysis, thrombocytosis, weight loss, an
      Eastern Cooperative Oncology Group performance status score of >=2 points,
      anemia, increased erythrocyte sedimentation rate, and increased alkaline
      phosphatase (AKP) and carcinoembryonic protein (CEA) levels were risk factors for
      bone metastasis. According to multivariate analysis, thrombocytosis, weight loss,
      and increased AKP and CEA levels were correlated with bone metastasis. Therefore,
      patients exhibiting pulmonary adenocarcinoma and thrombocytosis have a higher
      risk of bone metastasis compared with patients not exhibiting thrombocytosis.

PMID- 25621049
TI  - Antitumor effect of D-erythrose in an abdominal metastatic model of colon
      carcinoma.
AB  - Traditional chemotherapy drugs against colorectal cancer possess little or no
      specificity, leading to severe intolerable side-effects. Therefore, it is
      necessary to develop additional specific therapeutic strategies. It has been
      suggested that D-erythrose may specifically inhibit the growth of tumor cells.
      However, the in vivo antitumor effect of D-erythrose against colorectal cancer
      remains unknown. Thus, the present study investigated the antitumor effect of D
      erythrose in an abdominal metastatic model of colon carcinoma. Intraperitoneal
      (IP) colon carcinoma-bearing BALB/c mice received an IP injection of D-erythrose
      or normal saline (NS) daily for 15 days. The mice were weighed every three days.
      The tumor weights and the volume of ascites were evaluated following the
      treatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      assay was used to assess apoptosis in tumor tissues. The results revealed that D
      erythrose significantly reduced the weight of the intraperitoneal tumor by 69.1%,
      markedly inhibited the development of ascites and increased tumor cell apoptosis,
      without any observed toxic effects. These observations suggest that D-erythrose
      possesses antitumor activity against colon cancer. The present study may provide
      a potentially effective and specific approach for colon cancer treatment.

PMID- 25621050
TI  - A rare case of extra-adrenal pheochromocytoma localized to the ovary and detected
      via abdominal computed tomography angiography.
AB  - Extra-adrenal pheochromocytomas are rare tumors that originate from the
      chromaffin tissue of the sympathetic nervous system. Ovarian extra-adrenal
      pheochromocytoma is even more rare. The present study reports a rare case of an
      extra-adrenal pheochromocytoma that was localized to the right ovary, but was
      gynecologically asymptomatic. Computed tomography angiography (CTA) detected the
      tumor and indicated that it was well defined, highly vascularized and obtained
      its blood supply from the right ovarian artery. This is the second case of
      ovarian extra-adrenal pheochromocytoma reported in the literature, and the first
      description of the CTA manifestations in the ovary. Gynecologists and
      radiologists should consider the possibility that an ovarian mass could be an
      extra-adrenal pheochromocytoma, which would allow time to prepare appropriately
      for the surgical removal of the mass.

PMID- 25621051
TI  - Clinical characteristics and prognosis of primary pancreatic carcinoid tumors: A
      report of 13 cases from a single institution.
AB  - The present study aimed to analyze the diagnosis and treatment of 13 cases of
      pancreatic carcinoid tumors during a 56-year period at the Tianjin Medical
      University Cancer Institute and Hospital (Tianjin, China). The data from 13
      cases, consisting of 5 males and 8 females (mean age, 50 years), were collected
      and analyzed. Hematoxylin-eosin and immunohistochemistry staining were performed
      to investigate the expression of neuron-specific enolase (NSE), cytokeratin (CK),
      chromogranin A (CgA) and synaptophysin (Syn) in the tumors. The affected patients
      suffered abdominal and/or back pain without typical carcinoid syndrome. Radical
      resection was performed in 10 cases and regional resection in one case. The
      remaining two patients exhbited remote metastasis, and so were treated with
      single and double bypass surgery (choledochojejunostomy and
      gastrojejunostomy/choledochojejunostomy, respectively). The expression of CK,
      Syn, CgA and NSE was positive in nine (69.23%), 10 (76.92%), five (38.46%) and
      eight (61.54%) cases, respectively. The median survival time was 26.6 months. In
      conclusion, in patients with pancreatic carcinoid tumors that exhibit no typical
      carcinoid syndrome, such as those in the present study, the diagnosis can be
      confirmed by pathological examination and surgery is the most effective
      treatment.

PMID- 25621052
TI  - Phospho-PRAS40Thr246 predicts trastuzumab response in patients with HER2-positive
      metastatic breast cancer.
AB  - Resistance to trastuzumab is frequently observed during the treatment of patients
      with human epidermal growth factor 2 (HER2)-positive metastatic breast cancers.
      The aim of the present study was to determine if the phosphorylated proline-rich
      Akt substrate of 40 kDa (phospho-PRAS40Thr246), a novel biomarker for
      phosphoinositol-3 kinase (PI3K) pathway activation, could predict the response of
      HER2-positive metastatic breast cancers to treatment with trastuzumab. Formalin
      fixed, paraffin-embedded tumor tissue samples were retrospectively collected from
      55 trastuzumab-treated patients. Next, the expression of phospho-PRAS40Thr246 and
      phosphatase and tensin homolog (PTEN) was assessed by immunohistochemistry. In
      total, five common phosphoinositol-3 kinase alpha catalytic subunit mutations,
      namely E542K, E545K, E545D, H1047R and H1047L, were identified by the
      amplification-refractory mutation system, using the allele-specific polymerase
      chain reaction. The activation of the PI3K pathway, as determined by low PTEN
      expression or the presence of oncogenic PIK3CA mutations, was observed in 49.1%
      (27 cases) of the 55 HER2-positive metastatic breast cancer tissues. In total,
      40% of the tumors were defined as being phospho-PRAS40Thr246-positive.
      Furthermore, the results revealed that phospho-PRAS40Thr246 expression was
      associated with the PI3K pathway activation status and an increased risk of tumor
      progression in HER2-positive metastatic breast cancer patients who had received
      trastuzumab-based therapy. Therefore, phospho-PRAS40Thr246 expression levels may
      reflect the PI3K pathway activation status and act as a biomarker for HER2
      amplified breast cancer patients who are unlikely to respond to trastuzumab-based
      therapy.

PMID- 25621053
TI  - Abnormal liver function induced by myofibroblastic sarcoma infiltrating the
      liver: A case report.
AB  - Myofibroblastic sarcoma (MS) is a rare disease, which most frequently occurs in
      the head, neck and extremities. To the best of our knowledge, although a small
      number of studies have reported MS of the oral cavity, maxilla, tonsil, thyroid
      and tongue, MS of the liver and subsequent disabled liver function has not been
      previously reported. This study presents the case of a 38 year old female
      initially diagnosed and treated for a mass in the retroperitoneal region, who was
      subsequently diagnosed with MS of the liver three months following preliminary
      surgical treatment. The patient refused further treatment and was lost to follow
      up three months after discharge from the hospital. Clinical, biochemical and
      imaging observations, as well as pathological manifestations of the patient in
      the present case are discussed with the aim of increasing the knowledge of MS of
      the liver.

PMID- 25621054
TI  - Inhibitory effects of evodiamine on human osteosarcoma cell proliferation and
      apoptosis.
AB  - Osteosarcoma is a primary malignancy of bone, which is characterized by the
      proliferation of malignant mesenchymal cells, particularly in children and
      adolescents. Evodiamine is extracted from a variety of traditional Chinese
      medicines, which has been reported to induce apoptosis in certain tumors,
      including cervical, prostate and breast cancer, however, its effect on
      oestosarcoma cells remains unclear. The aim of the present study was to
      investigate the effect of evodiamine on osteosarcoma cell proliferation and
      apoptosis, and explore the associated underlying molecular mechanism. A Cell
      Counting Kit 8 assay was performed to detect the effects of evodiamine on the
      proliferation of human osteosarcoma U2OS cells. Annexin V-fluorescein
      isothiocyanate/propidium iodide staining was performed to analyze the apoptotic
      rate of the cells. The effect of evodiamine on the protein expression levels of B
      cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and survivin
      were detected by performing western blot analysis. Evodiamine inhibited the
      growth of human osteosarcoma U2OS cells by inhibiting cell proliferation and
      inducing cell apoptosis. Western blotting demonstrated that evodiamine
      downregulated the expression of Bcl-2, caspase-3 and survivin, and upregulated
      the expression of Bax in human osteosarcoma cells. Evodiamine effectively
      inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose
      dependent manner via downregulation of Bcl-2, caspase-3 and survivin protein
      expression levels and upregulation of Bax protein expression levels.

PMID- 25621056
TI  - Metastasis of the liver with a granulosa cell tumor of the ovary: A case report.
AB  - The present study describes the case of a 62 year-old female patient with a
      metastatic tumor in the right hemi-liver of >25 cm in diameter, who presented to
      The Affiliated Hospital of Guilin Medical University (Guangxi, China) with acute
      abdominal pain and severe malnutrition. Radical surgery was performed to remove
      the tumor by open surgery. A biopsy was not performed prior to the surgery, so
      the tumor was diagnosed as end-stage primary liver cancer (PLC) based solely on
      the character and appearance of the tumor on computed tomography prior to
      surgery. However, subsequent to the surgery, upon analysis by the Department of
      Pathology, the mass was identified as an ovarian granulosa cell tumor (GCT).
      These tumors occur rarely, representing only 2-3% of all ovarian tumors, and are
      well known for late recurrences, with an incidence of 25-30%. As metastasis of
      the liver with GCT is extremely rare and the data available on the subject is
      limited by the small number of studies, and due to the absence of a biopsy report
      prior to surgery, the patient was initially misdiagnosed with PLC. However,
      despite this misdiagnosis, a good result was obtained, as the patient was later
      diagnosed with GCT following a detailed pathological examination and was treated
      with rational therapy. The performance status and quality of life were
      significantly improved, and the patient remains disease-free at one year post
      surgery.

PMID- 25621055
TI  - Expression and significance of glucose transporter-1, P-glycoprotein, multidrug
      resistance-associated protein and glutathione S-transferase-pi in laryngeal
      carcinoma.
AB  - Increasing glucose transporter-1 (GLUT-1) activity is one of the most important
      ways to increase the cellular influx of glucose. We previously demonstrated that
      increased GLUT-1 expression was an independent predictor of survival in patients
      with laryngeal carcinoma. Thus, GLUT-1 may present a novel therapeutic target in
      laryngeal carcinoma. In this study, the expression of GLUT-1, P-glycoprotein (P
      gp), multidrug resistance-associated protein 1 (MRP1) and glutathione S
      transferase-pi (GST-pi) in laryngeal carcinomas was investigated by
      immunohistochemistry. Additionally, possible correlations between GLUT-1 and P
      gp, MRP1 and GST-pi and various clinicopathological parameters were analyzed. In
      this study, 52.9% (18/34), 58.8% (20/34), 20.6% (7/34) and 58.8% (20/34) of the
      laryngeal carcinomas were positive for GLUT-1, P-gp, MRP1 and GST-pi,
      respectively. The expression of GLUT-1, P-gp, MRP1 and GST-pi was higher in
      laryngeal carcinoma specimens when compared with laryngeal precancerous lesions
      (P<0.05). Pearson's correlation analysis showed correlations between GLUT-1 and P
      gp (r=0.364; P=0.034), GLUT-1 and MRP1 (r=0.359; P=0.037) and P-gp and GST-pi
      (r=0.426; P=0.012). GLUT-1 expression was found to significantly correlate with
      tumor-node-metastasis classification (P=0.02) and clinical stage (P=0.037).
      Furthermore, P-gp was found to significantly correlate with clinical stage
      (P=0.026). Univariate analysis showed that MRP1 expression was significantly
      associated with poor survival (c2=5.16; P=0.023). Multivariate analysis revealed
      that lymph node metastasis (P=0.009) and MRP1 overexpression (P=0.023) were
      significant predictors of poor survival. In the present study, the expression of
      GLUT-1, P-gp, MRP1 and GST-pi in laryngeal carcinomas was investigated, as well
      as the correlations between these proteins. P-gp was found to significantly
      correlate with clinical stage, while MRP1 overexpression was significantly
      associated with poor survival.

PMID- 25621057
TI  - Blastic plasmacytoid dendritic cell neoplasm presenting with a cutaneous tumor
      alone as the first symptom of onset: A case report and review of literature.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly named cluster of
      differentiation (CD)4+/CD56+ haematodermic neoplasm or blastic natural killer
      cell lymphoma, is a rare and highly aggressive haematopoietic malignancy. BPDCN
      typically occurs in the elderly, with a marked predilection for cutaneous
      involvement. The present study describes a case of BPDCN occurring in a 79-year
      old male. The patient presented with skin lesions alone, with no evidence of
      extracutaneous involvement during the course of the disease. BPDCN was diagnosed
      based on histological and immunohistochemical observations and the patient was
      subsequently treated with local radiotherapy alone. However, rapid disease
      progression occurred and the patient succumbed five months after being diagnosed.
      The current result therefore demonstrated that BPDCN is highly aggressive even
      without systemic dissemination, and that radiotherapy appears to be ineffective
      in treating this tumor. The present study emphasizes the importance of
      pathologists and dermatologists being aware of this uncommon disease in order to
      avoid misdiagnosis.

PMID- 25621058
TI  - Infiltrating angiolipoma of the lower lip: A case report and literature review.
AB  - Infiltrating angiolipoma (IAL) is a rare lesion and is a clinicopathological
      variant of angiolipoma. IAL occurs most commonly in the trunk and extremities, it
      is rarely found in the head and neck regions and extremely rare in the oral
      cavity. This study presents the case of a 74-year-old female with IAL of the
      lower lip. To the best of our knowledge, this is the first case of IAL arising in
      the lower lip to be reported. Microscopically, IAL was unencapsulated and mature
      lipocytes were separated by a branching network of proliferating small vessels
      that infiltrated the adjacent tissues. Therefore, complete excision was difficult
      to perform. Magnetic resonance imaging has been reported to be valuable in
      determining the extent of the tumor and asserting a preoperative diagnosis.
      According to previous studies, the recurrence rate of IAL following surgical
      extirpation is 35-50%. Furthermore, the levels of mRNA expression of the vascular
      endothelial growth factor (VEGF) family members in the tumor were investigated.
      VEGF-A and -B expression were detected, however, VEGF-C and -D were expressed at
      extremely low levels. Excisional biopsy was performed under local anesthesia.
      During four years of follow-up, no evidence of tumor recurrence had been
      identified. An operating microscope may be utilized for the total removal of an
      IAL to minimize damage to normal tissues. This report indicates that mast cell
      derived VEGF may be responsible for the enhanced vascularity in the tumor. We
      would therefore consider careful extirpation with no wide safety margin to be the
      procedure of choice, except when the tumor invades irregularly into the muscles.

PMID- 25621059
TI  - Prognostic effect of peripheral blood cell counts in advanced diffuse large B
      cell lymphoma treated with R-CHOP-like chemotherapy: A single institution
      analysis.
AB  - The primary objective of the present study was to correlate blood cell counts
      (lymphocyte, monocyte and platelet counts) with early disease relapse following
      the attainment of complete remission (CR) by the rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisolone (R-CHOP)-like regimen in patients with
      advanced diffuse large B-cell lymphoma (DLBCL). In total, 30 patients were
      evaluated, with a median follow-up period of 43 months. All the participating
      patients attained CR. In total, eight patients experienced relapse within two
      years of the diagnosis, and the three-year overall survival rate was recorded as
      77%. The peripheral counts for lymphocytes, monocytes and platelets, and the
      lymphocyte-monocyte ratio, all of which have been reported to be prognostic in
      DLBCL, were assessed. None of these parameters were correlated with the incidence
      of early relapse or with the prognosis. The lymphocyte count was higher in the
      patients with durable remission than in those who relapsed, however, no
      significant differences were identified. Thus, the present study concluded that
      early disease relapse was not predicted by peripheral blood cell counts in
      advanced DLBCL that reached CR using the R-CHOP-like regimen.

PMID- 25621060
TI  - Construction and detection of the tissue-specific pINV-HPV16 E6/7 vector.
AB  - A tissue-specific promoter can control downstream gene expression in tissues or
      organs. The human involucrin (hINV) promoter (pINV) that contains 2474 bp of hINV
      upstream sequence is able to regulate tissue-specific gene expression. This
      tissue specificity may be important for the prevention and treatment of human
      papilloma virus infections. pINV was cloned by polymerase chain reaction and the
      human papillomavirus (HPV)16 E6/7 gene was obtained from the cancer tissue
      samples of patients with cervical carcinoma at the Yangzhou Maternal and China
      Health-Care Center of Jinagsu Province (Yangzhou, China). First, specific primers
      were designed according to the genomic DNA sequence of the HPV16-type standard
      strain that has been reported and the E6/7 gene was acquired by PCR. The
      carcinogenic fraction of the E6/7 gene was removed and the remaining section was
      cloned into T vectors, sequenced correctly and then cloned into the eukaryotic
      expression vector pCEP4, which was lacking the CMV promoter. The positive
      recombinants were identified using blue-white screening and endonuclease
      digestion, subsequent to sequencing and analysis, and the tissue-specific
      recombinant pINV-HPV16E6/7 plasmids was detected.

PMID- 25621061
TI  - MicroRNA-133a suppresses colorectal cancer cell invasion by targeting Fascin1.
AB  - MicroRNAs (miRs) are a type of small non-coding RNA molecule that are involved in
      gene silencing and the regulation of cancer progression; miR-133a in particular
      has been implicated in colorectal cancer, although its specific role and
      underlying mechanism have yet to be determined. In the present study, the
      expression level of miR-133a was significantly downregulated in a number of
      colorectal cancer cell lines, as well as in colorectal cancer tissues compared
      with the normal adjacent tissues. Furthermore, the Fascin1 (FSCN1) gene was
      identified as a direct target of miR-133a, and the protein expression level of
      FSCN1 was negatively regulated by miR-133a in colorectal cancer cells.
      Additionally, restoration of miR-133a expression and downregulation of FSCN1
      protein expression suppressed colorectal cancer cell invasion, while
      overexpression of FSCN1 reversed the inhibitory effect of miR-133a upregulation
      on colorectal cancer cell invasion. Thus, the present data indicates that miR
      133a may at least partially suppress colorectal cancer cell invasion, possibly
      via the inhibition of FSCN1 expression. The present study highlights the
      important role of miR-133a in the progression of colorectal cancer.

PMID- 25621062
TI  - Investigating the role of introns in the regulation of regenerating gene 1
      expression.
AB  - Gastrin is a hormone that physiologically regulates gastric acid secretion and
      contributes to the maintenance of gastric epithelial architecture by regulating
      the expression of genes such as regenerating gene 1 (Reg1). Reg1 is involved in
      gastric carcinogenesis as an antiapoptotic factor. The current study explores the
      molecular mechanism of gastrin-regulated Reg1 expression in human gastric cancer
      cells. In total, five intron fragments of the Reg1 gene were cloned by polymerase
      chain reaction and inserted into luciferase reporter vector pGL3 to construct
      intron-luciferase reporter vectors. After confirmation by Xho I/Hind III
      digestion and DNA sequencing, the five constructs were transfected into the
      SGC7901 gastric cancer cell line. The luciferase activity of the cells
      transfected with each of the five constructs was detected following incubation
      without or with gastrin. The five intron fragments of Reg1 were also randomly
      labeled with digoxin as a probe, and nuclear proteins of gastric cancer cells
      were extracted following treatment with or without gastrin. Southwestern blotting
      was subsequently performed to detect transcription factors that bind to the
      introns. The results indicated that the luciferase activity was significantly
      higher in cells transfected with recombinant vectors containing introns 2, 3, 4
      or 5 than that in the cells transfected with an empty vector (P<0.05). However,
      no statistically significant difference in luciferase activity was identified
      between cells transfected with pGL3-intron 1 and those transfected with pGL3
      Basic (P>0.05). Following incubation with gastrin, no significant difference was
      identified (P>0.05). The five introns of Reg1 can bind a number of transcription
      factors and gastrin may affect this interaction. Introns 2-5 of Reg1 potentially
      have transcriptional control over gene expression in gastric cancer cells. In
      conclusion, gastrin may regulate the expression of the Reg1 gene via the
      interaction of the introns by binding to the transcription factors.

PMID- 25621063
TI  - Activation of the intrinsic apoptosis pathway contributes to the induction of
      apoptosis in hepatocellular carcinoma cells by valproic acid.
AB  - The level of histone deacetylation is closely associated with the genesis and
      development of tumors, but the antitumor effect and mechanism of the class I
      histone deacetylase inhibitor (HDACI) valproate acid sodium (VPA) on
      hepatocellular carcinoma cells has not been clearly demonstrated. In the present
      study, the antitumor effect and mechanism of VPA were measured in vitro. Firstly,
      it was found that, as an HDAC inhibitor, VPA could inhibit HDAC activity and
      HDAC1 gene expression in hepatocellular carcinoma cells and, as a result, an
      inhibition of cell proliferation was detected by MTT assay. Subsequently, the
      cell cycle and cell apoptosis profiles were analyzed using flow cytometry (FCM).
      The expression of the mRNA and protein of cyclins A, D1 and E and P21Waf/cip1 was
      measured by reverse transcription-polymerase chain reaction and FCM analysis to
      determine the molecular mechanism of VPA-induced cell cycle arrest. The activity
      and mRNA and protein expression of caspases 3, 8 and 9 were detected to determine
      the apoptotic pathway. Caspase expression was blocked by caspase inhibitors in
      order to observe whether the intrinsic or extrinsic pathway contributed to HepG2
      cell apoptosis. The results revealed that the mRNA and protein expression of
      cyclins A and D1 was downregulated while the expression of P21Waf/cip1 was
      upregulated by VPA. The expression of cyclin E was only slightly affected by VPA.
      The mRNA and protein expression and activity of caspases 3 and 9 were upregulated
      by VPA. By contrast, inhibitors of caspases 3 and 9 could reverse cell apoptosis
      and there was no notable change in caspase 8 expression in any of these
      experiments. The intrinsic apoptosis pathway, but not the death receptor pathway,
      contributed to the induction of apoptosis in hepatocellular carcinoma cells.
      Furthermore, VPA could inhibit the proliferation of hepatocellular carcinoma
      cells by inducing G1 phase arrest and cell apoptosis. These effects were
      attributed to the change in the caspase level.

PMID- 25621064
TI  - Superficial parotidectomy versus partial superficial parotidectomy in treating
      benign parotid tumors.
AB  - The aim of the present study was to compare the outcomes of superficial
      parotidectomy (SP) and partial superficial parotidectomy (PSP) in treating benign
      parotid tumors. Individuals who had undergone SP or PSP between 2005 and 2008
      were enrolled, the medical records were reviewed, and a questionnaire was created
      and mailed to the patients. For the statistical analysis, chi2 and non-parametric
      Mann-Whitney tests were used to analyze the variables. In total, 320 patients
      were included in the present study. Within the PSP group, immediate facial nerve
      weakness occurred in six patients (7.6%), and Frey's syndrome occurred in five
      (6.3%). Despite this, facial nerve function recovered fully during the follow-up,
      and recurrence was not identified. Within the SP group, Frey's syndrome occurred
      in 38 patients (15.8%), immediate facial nerve weakness in 55 patients (22.8%)
      and permanent facial nerve dysfunction in two patients (0.8%). However, no
      recurrence was evident. In total, 216 (67.5%) patients returned the
      questionnaire. Those with PSP demonstrated improved scores in the domains of
      appearance, facial contours, facial nerve function and Frey's syndrome. Compared
      with SP, PSP not only decreased the incidence of Frey's syndrome and transient
      facial nerve weakness, but also improved quality of life outcomes and guaranteed
      a low recurrence rate.

PMID- 25621065
TI  - Ursolic acid inhibits the invasive phenotype of SNU-484 human gastric cancer
      cells.
AB  - Metastasis is a major cause of cancer-related mortality in patients with gastric
      cancer. Ursolic acid, a pentacyclic triterpenoid compound derived from medicinal
      herbs, has been demonstrated to exert anticancer effects in various cancer cell
      systems. However, to the best of our knowledge, the inhibitory effect of ursolic
      acid on the invasive phenotype of gastric cancer cells has yet to be reported.
      Therefore, the aim of the present study was to investigate the effect of ursolic
      acid on the invasiveness of SNU-484 human gastric cancer cells. Ursolic acid
      efficiently induced apoptosis, possibly via the downregulation of B-cell lymphoma
      2 (Bcl-2), the upregulation of Bcl-2-associated X protein and the proteolytic
      activation of caspase-3. Furthermore, the activation of p38 mitogen-activated
      protein kinase and c-Jun N-terminal kinase was increased by the administration of
      ursolic acid. In addition, ursolic acid significantly suppressed the invasive
      phenotype of the SNU-484 cells and significantly decreased the expression of
      matrix metalloproteinase (MMP)-2, indicating that MMP-2 may be responsible for
      the anti-invasive activity of ursolic acid. Taken together, the results of the
      present study demonstrate that ursolic acid induces apoptosis and inhibits the
      invasive phenotype of gastric cancer cells; therefore, ursolic acid may have a
      potential application as a chemopreventive agent to prevent the metastasis of
      gastric cancer or to alleviate the process of metastasis.

PMID- 25621066
TI  - Coexisting intramedullary schwannoma with an ependymal cyst of the conus
      medullaris: A case report.
AB  - Synchronous spinal intramedullary ependymal cysts and intramedullary schwannomas
      are rare. To the best of our knowledge, the present study is the first report of
      a case of intramedullary schwannoma coexisting with an ependymal cyst. A 35-year
      old male presented with lower back pain and weakness in the left leg. Magnetic
      resonance imaging identified an intramedullary cystic-solid lesion at the
      thoracolumbar junction of T11-L2; based on the clinical presentation and
      radiological features, a pre-operative diagnosis of ependymoma was formed.
      Subsequently, the patient underwent a T11-12 laminectomy via a posterior
      approach, with intraoperative monitoring of somatosensory and motor-evoked
      potentials, achieving a gross total resection of the tumor with a well-demarcated
      dissection plane. Post-operative histopathological examination demonstrated a
      schwannoma coexisting with the ependymal cyst, and the neurological status of the
      patient markedly improved compared with the pre-operatively observed neurological
      deficit.

PMID- 25621067
TI  - Borderline epithelial tumors of the ovary: Experience of 55 patients.
AB  - The objective of the present study was to evaluate the clinicopathological
      features and the survival time estimates in patients treated for borderline
      ovarian tumors (BOTs). A retrospective review of all patients treated for BOTs at
      the University of Bari (Bari, Italy) between 1991 and 2011 was performed. Data
      were obtained from hospital records and gynecological oncology charts. A total of
      55 patients were identified. The median age was 40 years (range, 13-79 years).
      The majority of the patients (85.5%) exhibited International Federation of
      Obstetrics and Gynecology (FIGO) stage I disease and the remainder exhibited FIGO
      stage II/III (7.3% in each stage). Serous histology was found in 60.0% of the
      cases and an elevation of the cancer antigen-125 serum level occurred in 23.6% of
      the cases. All patients underwent surgery and 3.7% received chemotherapy. In
      total, 10.9% exhibited recurrence and the median survival rate was 39 months. The
      median survival time and the five-year survival rate were 42 months (range, 16-84
      months) and 97%, respectively. Therefore, BOTs have an excellent prognosis.
      Conservative surgery should be considered for patients of reproductive age who
      desire preservation of fertility. A long-term follow-up is highly recommended for
      these tumors.

PMID- 25621068
TI  - Expression levels of matrix metalloproteinase-9 in human gastric carcinoma.
AB  - The present report investigated the correlation between the expression levels of
      matrix metalloproteinase (MMP)-9 in gastric carcinoma patients and the
      clinicopathological characteristics. Forty-five samples of gastric carcinoma and
      distal gastric mucosa tissue, and 10 samples of healthy gastric mucosa tissue
      were analyzed using semi-quantitative polymerase chain reaction, as well as
      immunohistochemical and hematoxylin and eosin staining. MMP-9 protein levels in
      serum samples from the same patients were quantified by enzyme-linked
      immunosorbent assay. The present report identified that MMP-9 expression was
      markedly higher in the gastric carcinoma tissue (86.67%) than in the adjacent
      healthy tissue (10.00%). A positive association was identified between the level
      of MMP-9 protein expression and the depth of cancer invasion (P<0.05).
      Furthermore, the preoperative serum levels of the MMP-9 protein in the gastric
      carcinoma tissue were correlated with the tumor-node-metastasis stage and
      occurrence of lymph node metastasis (P<0.01). Data from the present report
      indicates that MMP-9 may be key in gastric carcinoma malignancy, and implies that
      MMP-9 may serve as a novel biomarker in the diagnosis and prognosis of gastric
      carcinoma.

PMID- 25621069
TI  - Post-infectious myositis ossificans in medial, lateral pterygoid muscles: A case
      report and review of the literature.
AB  - Myositis ossificans (MO) is a disease where heterotropic bone forms within a
      muscle or other type of soft tissue. MO is classified into two groups, MO
      progressiva and post-traumatic MO. It rarely occurs in the masticatory muscles
      and thus, only 20 cases involving the masticatory muscles have been reported
      since 2001. The majority of the reported cases occurred due to trauma, repeated
      injury or surgical manipulation. However, in a small number of cases, no specific
      traumatic event was identified as the cause of MO. To the best of our knowledge,
      this is the first case of post-infectious MO to be reported in the medial and
      lateral pterygoid muscles.

PMID- 25621070
TI  - Molecular analysis of human papillomavirus in never-smokers with non-small cell
      lung cancer.
AB  - The causes of lung cancer in never-smokers remain unclear. The potential
      contribution of human papillomavirus (HPV) to the carcinogenesis of non-small
      cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of
      never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center,
      Sakai, Osaka, Japan. Never-smokers with NSCLC were consecutively enrolled onto
      the registry. Of these patients, 114 with large tumor specimens, the majority of
      which were surgical tissues, were selected. In total, 23 of the most clinically
      relevant HPV types were assayed using polymerase chain reaction amplification of
      the viral genome. Following exclusion of samples with suboptimal quality, DNA was
      extracted from 96 formalin-fixed paraffin-embedded samples. These 96 cases
      consisted of 82 females (85.4%) and 14 males (14.6%), with a median age of 67
      years (range, 29-83). Almost all cases (93.8%) were of the adenocarcinoma
      histological subtype. Despite confirmation of the quality and amount of DNA, HPV
      type 6 was detected in only one case (1.1%). Furthermore, no other samples
      examined were positive for any other HPV types. The results therefore suggest
      that HPV does not play a major role as the driving oncogenic event in never
      smokers with NSCLC.

PMID- 25621071
TI  - Broca's aphasia due to cerebral venous sinus thrombosis following chemotherapy
      for small cell lung cancer: A case report and review of literature.
AB  - Cancer is associated with an increased risk of cerebrovascular incidents and
      treatment with chemotherapy enhances that risk further. Brocha's aphasia is a
      stroke-related syndrome, the presentation of which has been rarely reported
      during cisplatin-based chemotherapy. The current study presents the case of a 27
      year-old male with advanced-stage small cell lung cancer. The patient developed
      Broca's aphasia following cisplatin-based chemotherapy.

PMID- 25621072
TI  - Mechanisms of methotrexate resistance in osteosarcoma cell lines and strategies
      for overcoming this resistance.
AB  - The aim of the present study was to investigate the underlying mechanisms of
      methotrexate (MTX) resistance in the human osteosarcoma cell line, Saos-2/MTX4.4,
      and to evaluate various methods of overcoming the resistance to this
      chemotherapeutic agent. MMT assays were performed to determine the resistance of
      the primary (Saos-2) and resistant (Saos-2/MTX4.4) cell lines to MTX, cisplatin
      [cis-diamminedichloroplatinum II (DDP)], ifosfamide (IFO), Adriamycin (ADM),
      epirubicin (EPI) and theprubicin (THP). The Saos-2/MTX4.4 cells exhibited a low
      resistance to IFO, ADM, EPI and THP; however, no resistance to DDP was
      identified. Overall, the Saos-2/MTX4.4 cells exhibited a greater resistance to
      all the chemotherapeutic agents investigated compared with the Saos-2 cells.
      Rhodamine 123 (R123) fluorescence was measured in the Saos-2/MTX4.4 and Saos-2
      cells 30 and 60 min after the addition of R123, and R123 plus verapamil (VER).
      VER administration increased the intracellular accumulation of R123. In addition,
      reverse transcription-quantitative polymerase chain reaction was performed to
      determine the mRNA expression levels of multidrug resistance gene 1 (MDR1) in the
      two cell lines. Although the Saos-2/MTX4.4 cells were more resistant to the
      chemotherapeutic agents than the Saos-2 cells, no significant difference was
      identified between the relative mRNA expression levels of MDR1 in the Saos
      2/MTX4.4 and Saos-2 cells (0.4350+/-0.0354 vs. 0.3886+/-0.0456; P>0.05).

PMID- 25621073
TI  - Secondary cancer in a survivor of Hodgkin's lymphoma: A case report and review of
      the literature.
AB  - Hodgkin's lymphoma (HL) is one of the most curable malignant diseases in adults.
      However, HL patients have a higher risk of developing second malignancies
      compared with the general population. The population of adult cancer survivors is
      growing, thus, the long-term effects of cancer treatment, including secondary
      cancer development, have become an increasingly important concern in the field of
      oncology. The current study presents the case of a female HL survivor who
      developed two secondary malignancies within 29 years of follow-up. Furthermore, a
      review of the literature was conducted, which focused on secondary breast and
      gastrointestinal cancers in HL survivors.

PMID- 25621074
TI  - MiR-30a upregulates BCL2A1, IER3 and cyclin D2 expression by targeting FOXL2.
AB  - FOXL2 is a transcription factor that is essential for ovarian development.
      Somatic mutations of FOXL2 are associated with ovarian granulosa cell
      tumorigenesis. In the present study, the expression of FOXL2 was suppressed by
      microRNAs using the Ago2 knockdown method in COV434 cells. Online bioinformatics
      tools were utilized to predict that FOXL2 expression may be repressed by miR-30
      family members, and dual luciferase assay and western blotting were performed to
      demonstrate that FOXL2 is a target gene of miR-30a, which is relatively abundant
      in COV434 cells. Furthermore, miR-30a overexpression upregulates BCL2A1, IER3 and
      cyclin D2 expression by inhibiting FOXL2. miR-30a is known to function as a tumor
      suppressor in breast cancer, small cell lung cancer and colorectal carcinoma;
      however, the present study revealed an opposing function of miR-30a as an
      oncogene.

PMID- 25621075
TI  - Solitary fibrous tumor of the submandibular region.
AB  - Solitary fibrous tumors (SFTs) are a rare type of neoplasm that originate from
      the pleura. Although SFTs may occur in a variety of extrathoracic regions, they
      are considered to be rare in the submandibular region. The current study presents
      the case of a 39-year-old female with a 3*4-cm, fibro-elastic, movable, painless
      nodule in the right side of the submandibular region. The patient exhibited no
      other clinical manifestations in the head and neck region. A computed tomography
      scan demonstrated the presence of a well-defined, slightly low-density nodular
      shadow measuring 2.6*3.3*3.8 cm, in proximity to the right submandibular gland,
      with mild contrast enhancement and no association with the adjacent lymph nodes.
      The lesion was surgically excised, and following histopathological and
      immunohistochemical analysis, immunohistochemical staining determined that the
      lesion was positive for cluster of differentiation (CD)34, CD99 and vimentin, and
      negative for desmin, CD31 and S-100; therefore, a diagnosis of an SFT was
      determined. The patient has so far been followed up for 22 months, with no signs
      of recurrence or metastases. The present study also discusses the clinical,
      histopathological and immunohistochemical features, treatment strategies and
      potential clinical outcomes of SFTs. The study proposes that, although rare, SFTs
      of the submandibular region should be included in the differential diagnosis of
      soft-tissue tumors in the submandibular region.

PMID- 25621076
TI  - First-line chemotherapy with docetaxel plus capecitabine followed by capecitabine
      or hormone maintenance therapy for the treatment of metastatic breast cancer
      patients.
AB  - The primary aim of the present study was to evaluate whether maintenance therapy
      with capecitabine or hormone replacement therapy (HRT) results in improved
      progression-free survival (PFS) in metastatic breast cancer (MBC) patients who
      had previously achieved disease control with first-line docetaxel plus
      capecitabine (TX) chemotherapy. Seventy-nine metastatic breast cancer patients
      treated between January 2008 and June 2013 with TX chemotherapy were
      retrospectively analyzed. Following successful initial disease control by the
      combination chemotherapy, 39 patients received single-agent capecitabine
      maintenance therapy and 40 patients received HRT as maintenance therapy. The PFS
      time, objective response rate, clinical benefit rate and safety of the two groups
      were compared. The median PFS of the total cohort (n=79) was 11.0 months.
      Furthermore, the median PFS time of the capecitabine (n=39) and HRT groups (n=40)
      were 10.9 and 11.1 months, respectively (P=0.283). Compared with the PFS time of
      maintenance treatment only, single-agent capecitabine treatment following TX
      chemotherapy prolonged the PFS time by 6.8 months and HRT following TX
      chemotherapy prolonged PFS time by 5.8 months (P=0.551). Of the total cohort, 49
      patients did not receive palliative endocrine therapy prior to chemotherapy,
      including 22 patients in the capecitabine maintenance group and 27 patients in
      the HRT maintenance group. The PFS time from the commencement of maintenance
      treatment was significantly different between the two groups, 6.1 months in the
      capecitabine group compared with 11.5 months in the HRT group (P=0.045). For the
      30 patients who underwent palliative endocrine therapy prior to TX chemotherapy,
      the PFS times of the capecitabine and HRT maintenance treatment groups were 7.5
      and 4.1 months, respectively (P=0.043). However, the occurrence of adverse
      events, such as hematological and gastrointestinal toxicity, as well as hand-foot
      syndrome, were not significantly different between the two groups. The current
      study indicated that single-agent capecitabine maintenance therapy may be a
      potential treatment strategy for MBC patients who responded to capecitabine-based
      chemotherapy. In particular, capecitabine may provide a more effective
      maintenance treatment duration compared with HRT for patients who had previously
      undergone first-line palliative HRT for MBC.

PMID- 25621077
TI  - Goyazensolide Induces Apoptosis in Cancer Cells in vitro and in vivo.
AB  - As part of the screening program for anticancer agents from natural sources, the
      sesquiterpene lactone goyazensolide (GZL) was identified as a potent NF-kappaB
      inhibitor. The hollow-fiber assay was used to evaluate the anti-tumor efficacy of
      GZL in vivo. The mechanistic effects of GZL were evaluated in the HT-29 colonic
      cell line to reveal the pathway through which GZL exerts its effects. NF-kappaB
      subunits p65 and p50 were inhibited, and the upstream mediator IkappaB kinase
      (IKKbeta) was downregulated in a dose-dependent manner. Apoptosis was mediated by
      caspase-3, and cell cycle arrest was detected in G1-phase. Consequently, 96% of
      the cell population was in sub G1-phase after treatment with GZL (10 MUM).The
      antitumor effect of GZL was observed at a dose of 12.5 mg/kg. Cell adhesion was
      affected as a result of NF-kappaB inhibition. GZL appears to selectively target
      the transcription factor NF-kappaB. In summary, GZL sensitizes HT-29 colon cancer
      cells to apoptosis and cell death in a dose-dependent manner both in vivo and in
      vitro, through NF-kappaB inhibition (IC50 = 3.8 MUM). Thus, it is a new potent
      lead compound for further development into a new effective chemotherapeutic
      agent.

PMID- 25621078
TI  - Predicting outcomes in patients with perforated gastroduodenal ulcers: artificial
      neural network modelling indicates a highly complex disease.
AB  - PURPOSE: Mortality prediction models for patients with perforated peptic ulcer
      (PPU) have not yielded consistent or highly accurate results. Given the complex
      nature of this disease, which has many non-linear associations with outcomes, we
      explored artificial neural networks (ANNs) to predict the complex interactions
      between the risk factors of PPU and death among patients with this condition.
      METHODS: ANN modelling using a standard feed-forward, back-propagation neural
      network with three layers (i.e., an input layer, a hidden layer and an output
      layer) was used to predict the 30-day mortality of consecutive patients from a
      population-based cohort undergoing surgery for PPU. A receiver-operating
      characteristic (ROC) analysis was used to assess model accuracy. RESULTS: Of the
      172 patients, 168 had their data included in the model; the data of 117 (70%)
      were used for the training set, and the data of 51 (39%) were used for the test
      set. The accuracy, as evaluated by area under the ROC curve (AUC), was best for
      an inclusive, multifactorial ANN model (AUC 0.90, 95% CIs 0.85-0.95; p < 0.001).
      This model outperformed standard predictive scores, including Boey and PULP. The
      importance of each variable decreased as the number of factors included in the
      ANN model increased. CONCLUSIONS: The prediction of death was most accurate when
      using an ANN model with several univariate influences on the outcome. This
      finding demonstrates that PPU is a highly complex disease for which clinical
      prognoses are likely difficult. The incorporation of computerised learning
      systems might enhance clinical judgments to improve decision making and outcome
      prediction.

PMID- 25621079
TI  - Age and Sex Effects in Anchoring Vignette Studies: Methodological and Empirical
      Contributions.
AB  - Anchoring vignettes are an increasingly popular tool for identifying and
      correcting for group differences in use of subjective ordered response
      categories. However, existing techniques to maximize response consistency (use of
      the same standards for self-ratings as for vignette-ratings), which center on
      matching vignette characters' demographic characteristics to respondents' own
      characteristics, appear at times to be ineffective or to pose interpretive
      difficulties. Specifically, respondents often appear to neglect instructions to
      treat vignette characters as age peers. Furthermore, when vignette characters'
      sex is matched to respondents' sex, interpretation of sex differences in rating
      style is rendered problematic. This study applies two experimental manipulations
      to a national American sample (n=1,765) to clarify best practices for enhancing
      response consistency. First, an analysis of two methods of highlighting vignette
      characters' age suggests that both yield better response consistency than
      previous, less prominent means. Second, a comparison of ratings of same- and
      opposite-sex vignette characters suggests that, with avoidable exceptions, the
      sex of the respondent rather than of the vignette character drives observed sex
      differences in rating style. Implications for interpretation and design of
      anchoring vignette studies are discussed. In addition, this study clarifies the
      importance of two additional measurement assumptions, cross-respondent vignette
      equivalence and cross-character vignette equivalence. It also presents empirical
      findings of significant sex, educational, and racial/ethnic differences in styles
      of rating health, and racial/ethnic differences in styles of rating political
      efficacy. These findings underscore the incomparability of unadjusted subjective
      self-ratings across demographic groups, and thus support the potential utility of
      the anchoring vignette method.

PMID- 25621080
TI  - "8 plate": an alternative device to fix highly recurrent traumatic anterior gleno
      humeral instability in patients with severe impairment of the anterior capsule.
AB  - BACKGROUND: There is still debate about the best treatment option for highly
      recurrent anterior shoulder dislocation in patients with severe impairment of the
      anterior capsule and/or recurrence after either arthroscopic or open
      capsulorrhaphy. Materials and. METHODS: The clinical and radiological findings of
      7 patients treated with an open capsulorrhaphy stabilized with an "8 plate" for a
      highly recurrent traumatic anterior shoulder dislocation with severe impairment
      of the anterior capsule and a large Bankart lesion were retrospectively reviewed.
      Follow-up evaluation included VAS for pain, Constant-Murley, Simple Shoulder
      Test, ASES, UCLA, Quick DASH, Rowe, Walsch-Duplay scores, as well as X-rays of
      the operated shoulder. RESULTS: At follow-up none of the patients reported
      subsequent dislocations. Range of motion of the shoulder was complete in all
      cases, but one. Results of the functional scoring systems were satisfactory. X
      rays showed no osteolysis and good position of the plate. CONCLUSION: To our
      knowledge, this is the first report in the literature about an open capsular
      tensioning and Bankart lesion repair performed with an "8 plate". We believe that
      this is a reliable and effective procedure to address traumatic anterior re
      dislocation of the gleno-humeral joint when the capsule is extensively torn and
      frayed or in revision cases. Moreover the "8 plate" is ideal to be applied in
      such a narrow space on the slant surface of the scapular neck close to the
      glenoid rim.

PMID- 25621081
TI  - Atypical carpal tunnel syndrome in a holt oram patient: a case report and
      literature review.
AB  - We present a case report of a patient diagnosed with Holt-Oram syndrome (HOS)
      presenting with clinical and electrophysiologically confirmed carpal tunnel
      syndrome. Pre-operative Magnetic resonance imaging revealed an abnormal course of
      the median nerve; as such an atypical incision and approach were carried out to
      decompress the nerve to excellent post operative clinical effect. To our
      knowledge this is the first description of abnormal nervous course in a patient
      with HOS leading to peripheral entrapment. A literature surrounding the important
      aspects of HOS to the orthopaedic surgeon is presented concomitantly. 

PMID- 25621082
TI  - Treatment of trochanteric fractures with the gamma3 nail - methodology and early
      results of a prospective consecutive monitored clinical case series.
AB  - OBJECTIVES: There is only sparse data on clinical results and complications of
      the third-generation Gamma nailing system (Gamma3, Stryker). Therefore, we
      started a large multi-centre case series in 2008. The aim of this paper is to
      present the study design and early results of a single arm of a prospective,
      consecutive, monitored, post-market follow-up evaluation of Gamma3 nails.
      METHODS: From September 2009 to January 2012, 154 consecutive patients with an
      average age of 80 +/- 1.43 years (50-99 years) and a trochanteric femoral
      fracture were included in the local arm of the trial. All patients that fulfilled
      the inclusion criteria were treated with a Gamma3 nail. Preoperative variables
      included age, gender, fracture classification, walking ability (Merle d'Aubigne
      score), daily activity level (retrospective Zuckerman score), ASA rating of
      operative risk, waiting time for operation, use of walker or crutches and body
      mass index (BMI). Skin-to-skin time, fluoroscopy time, blood loss, intraoperative
      complications and device information were recorded for each patient. Follow-up
      postoperative assessment was undertaken at 4, 12 and 24 months. Hip range of
      motion, pain around the hip and the tight, walking ability (Merle d'Aubigne
      score, Sahlgrenska mobility score) and management of daily life (Zuckerman score)
      were used to evaluate the outcome. RESULTS: The descriptive data of age, gender,
      BMI, ASA classification, fracture type and skin-to-skin time is similar to other
      studies. Median fluoroscopy time was 62 seconds (range: 4-225 seconds) and
      significantly shorter in closed reductions. No intraoperative implant-related
      complication was recorded. A cut-out of the leg-screw during assessment period
      occurred in 2.6% patients (n = 4). At the 12-month assessment two (1.8%) non
      unions were identified and two patients (1.8%) had broken the femoral shaft below
      the 180 mm nail after a fall. Analysis of the scores showed significantly
      declined mobility and activity in daily life four months after operation which
      increased significantly from four to 12 months and increased slightly between 12
      and 24 months after fracture. CONCLUSION: A low implant-associated complication
      rate was achieved in geriatric patients with trochanteric femoral fractures using
      the Gamma3 nail. A better outcome concerning mobility, activity in daily life and
      complications compared to the Gamma2 nail could not be found in comparison to
      historic data.

PMID- 25621083
TI  - Persistent wound drainage after tumor resection and endoprosthetic reconstruction
      of the proximal femur.
AB  - PURPOSE: To examine the prevalence of prolonged wound drainage (PWD) after tumor
      resection and endoprosthetic reconstruction of the hip. METHODS: Retrospective
      review of 86 consecutive patients with metastatic bone disease, malignant
      hematologic bone disease or bone sarcoma, treated with tumor resection and
      subsequent endoprosthetic reconstruction of the proximal femur, between 2010 and
      2012, in a single center. RESULTS: PWD for 7 days or more was observed in 41
      cases (48%). The wounds only ceased oozing after a mean of 8.4 days, leading to
      prolonged administration of prophylactic antibiotics (mean 8.7 days) and length
      of hospital stay (mean 10.2 days). Total femur replacement, bone sarcoma and
      additional pelvic reconstruction were identified as significant independent risk
      factors for an even longer duration of PWD. CONCLUSION: Compared to conventional
      hip arthroplasty, PWD appears to be significantly more prevalent in patients
      undergoing tumor arthroplasty procedures of the hip. Given the potentially
      increased risk for periprosthetic joint infection (PJI), increased awareness,
      identification and implementation of adequate strategies for prevention and
      treatment of this avoidable complication are warranted.

PMID- 25621084
TI  - Concomitant septic arthritis and tophaceous gout of the knee managed with
      intermittent closed joint irrigation combined with negative pressure therapy: a
      case study and literature review.
AB  - Tophaceous gout complicated by septic arthritis presents a management dilemma
      which can often require multiple surgical debridements. There is little published
      in the literature regarding treatment of these concomitant conditions. We
      postulate that biofilm may play a role increasing the difficulty of sterilising a
      tophaceous joint. The use of topical negative pressure therapy that targets
      biofilm has been well established for a range of wounds. A new device that
      incorporates both intermittent negative pressure therapy and wound irrigation was
      introduced in 2012. This case report describes the use of this topical negative
      device with the instillation option in the management of severe septic arthritis
      with concomitant gout and suggests directions for further research. 

PMID- 25621085
TI  - Simulation of windblown dust transport from a mine tailings impoundment using a
      computational fluid dynamics model.
AB  - Mining operations are potential sources of airborne particulate metal and
      metalloid contaminants through both direct smelter emissions and wind erosion of
      mine tailings. The warmer, drier conditions predicted for the Southwestern US by
      climate models may make contaminated atmospheric dust and aerosols increasingly
      important, due to potential deleterious effects on human health and ecology. Dust
      emissions and dispersion of dust and aerosol from the Iron King Mine tailings in
      Dewey-Humboldt, Arizona, a Superfund site, are currently being investigated
      through in situ field measurements and computational fluid dynamics modeling.
      These tailings are heavily contaminated with lead and arsenic. Using a
      computational fluid dynamics model, we model dust transport from the mine
      tailings to the surrounding region. The model includes gaseous plume dispersion
      to simulate the transport of the fine aerosols, while individual particle
      transport is used to track the trajectories of larger particles and to monitor
      their deposition locations. In order to improve the accuracy of the dust
      transport simulations, both regional topographical features and local weather
      patterns have been incorporated into the model simulations. Results show that
      local topography and wind velocity profiles are the major factors that control
      deposition.

PMID- 25621086
TI  - EPiK-a Workflow for Electron Tomography in Kepler.
AB  - Scientific workflows integrate data and computing interfaces as configurable,
      semi-automatic graphs to solve a scientific problem. Kepler is such a software
      system for designing, executing, reusing, evolving, archiving and sharing
      scientific workflows. Electron tomography (ET) enables high-resolution views of
      complex cellular structures, such as cytoskeletons, organelles, viruses and
      chromosomes. Imaging investigations produce large datasets. For instance, in
      Electron Tomography, the size of a 16 fold image tilt series is about 65
      Gigabytes with each projection image including 4096 by 4096 pixels. When we use
      serial sections or montage technique for large field ET, the dataset will be even
      larger. For higher resolution images with multiple tilt series, the data size may
      be in terabyte range. Demands of mass data processing and complex algorithms
      require the integration of diverse codes into flexible software structures. This
      paper describes a workflow for Electron Tomography Programs in Kepler (EPiK).
      This EPiK workflow embeds the tracking process of IMOD, and realizes the main
      algorithms including filtered backprojection (FBP) from TxBR and iterative
      reconstruction methods. We have tested the three dimensional (3D) reconstruction
      process using EPiK on ET data. EPiK can be a potential toolkit for biology
      researchers with the advantage of logical viewing, easy handling, convenient
      sharing and future extensibility.

PMID- 25621087
TI  - Different ontologies: land change science and health research.
AB  - Land use and land cover (LULC) is now recognized as an important driver of
      disease. For emerging or re-emerging infectious diseases, LULC offers context and
      serves as a likely proximate driver of risk particularly when considering vector
      borne or zoonotic diseases. Ontological differences embedded within disciplinary
      structures impede progress limiting the ultimate potential of both LULC data and
      land change theory within disease research. Geography, space, and time serve as
      effective complements to traditional health and place organizational and disease
      research strategies. Improved systemic clarity is obtained if one orients the
      disease relationship to particular contexts and if the scales of the
      relationships are clearly defined.

PMID- 25621088
TI  - Cutaneous abnormalities in patients with end stage renal failure on chronic
      hemodialysis. A study of 458 patients.
AB  - BACKGROUND: Cutaneous manifestations occurring in patients with end stage renal
      failure on hemodialysis are polymorphic and diverse. OBJECTIVE: The aim of our
      study was to assess the prevalence and characteristics of different cutaneous
      manifestations in patients on hemodialysis. PATIENTS AND METHODS: We led a
      transverse investigation of all patients on hemodialysis in 12 haemodialysis
      centres of Sfax (Tunisia). We examined 458 patients (254 men and 204 women). The
      hemodialysis history ranged from 6 months to 24 years. A total of 394/458 (86%)
      patients had cutaneous abnormalities. These included pruritus (56.6% of
      patients), paleness (60.7%), xerosis (52.8%), hyperpigmentation or
      hypopigmentation (38.4%), venous dilation near the fistula (22.2%), eczema in the
      fistula area (14.8%), half-and-half nails (13.5%), onychodystrophy (6.1%),
      subungual hemorrhage (4.5%), leukonychia (4.5%), stomatitis (5.6%), xerostomia
      (3.2%), gingivitis (2.4%), uremic breath (2.1%), and skin calcificatins (0.4%).
      Nephrogenic fibrosing dermopathy was not detected in any of our patients.
      CONCLUSIONS: Pruritus, paleness, dry skin as well as hyperpigmentation and
      hypopigmentation are the most frequent skin abnormalities observed in
      hemodialysis patients. The early recognition of some cutaneous conditions
      associated with end stage renal failure and hemodialysis may allow early
      therapeutic intervention and decrease morbidity.

PMID- 25621089
TI  - Dermatologic adverse events of protease inhibitor-based combination therapy in
      patients with chronic hepatitis C.
AB  - BACKGROUND: Combination therapy with pegylated interferon, ribavirin and a first
      generation NS3/4A protease inhibitor, telaprevir or boceprevir, is the new
      strategy for treatment of genotype 1 chronic hepatitis C virus infection. This
      combination improves therapeutic efficacy but it also increases the risk of
      adverse events. OBJECTIVE: The aim of the study was to analyze frequency and
      severity of dermatological adverse events during protease inhibitor-based therapy
      and to evaluate the risk factors for their development. PATIENTS AND METHODS:
      This is a retrospective study of 109 patients with genotype 1 chronic hepatitis C
      treated with boceprevir (n=33) or telaprevir (n=76) based triple therapy. A
      logistic regression for relationship between clinical, demographic and laboratory
      factors and cutaneous adverse events was performed. RESULTS: Dermatological
      adverse events (skin rash, pruritus, anorectal paresthesia) occurred in both
      treatments (boceprevir and telaprevir) with similar frequency: 28% in telaprevir
      and 21% in boceprevir. In patients treated with telaprevir, men were more
      predisposed to develop skin rashes compared to women (OR 4,1 p=0,014) and age
      above 45 years was associated with occurrence of pruritus in men (OR 8,16
      p=0,014). Being a female, coexistence of autoimmune thyroiditis and advanced
      liver fibrosis were independent factors predisposing to development of anorectal
      paresthesia (OR 4,13 p=0,041, OR 4,25 p=0,029, OR 4,54 p=0,018 respectively) in
      this group. In patients treated with boceprevir, coexistence of autoimmune
      thyroiditis predisposed to skin rashes (OR 10,22 p=0,017) and being a female
      predisposed to pruritus (OR11,2 p=0,033). The adverse events occurred after a
      mean time of 8,6 (range 1-24) weeks after initiation of therapy. CONCLUSIONS: In
      patients with chronic hepatitis C who received the triple therapy, the anorectal
      paresthesias were observed only in patients treated with telaprevir. The
      predisposing factors for this adverse event were: female gender and advanced
      liver fibrosis. The risk factors for other dermatological adverse were: 1) being
      a male over 45 years, for skin rashes and pruritus (for telaprevir), 2)
      coexistence of autoimmune thyroiditis for skin rashes (for boceprevir), 3) being
      a female, for pruritus (for boceprevir).

PMID- 25621090
TI  - Reconstructive surgery in advanced perioral non-melanoma skin cancer. Results in
      elderly patients.
AB  - BACKGROUND: Nonmelanoma skin cancer (NMSC) of the perioral region is not
      uncommon. Basal cell carcinoma is predominant in the upper lip area and squamous
      cell carcinoma in the lower lip area. While smaller lesions can be treated by
      excision followed by primary closure larger defects after tumor surgery can be
      challenging. OBJECTIVES: Analysis of outcome after complete surgical excision
      with micrographical control of excision margins (delayed Mohs surgery) of large
      NMSC's of the perioral region (lips and chin). PATIENTS AND METHODS: This is a
      retrospective, single-center analysis of patients with defects after delayed Mohs
      surgery of >= 3 cm of the perioral region. The study included a total of 25
      patients (4 women and 21 men) with a mean age of 83.7 years. Twenty patients were
      diagnosed with squamous cell carcinoma and five had basal cell carcinoma. The
      lower lip was affected in 19 patients, the upper lip in 4 patients and the chin
      in 2 patients. Tumor stage was either T1N0M0 or T2N0M0. The most common procedure
      for lower lip defect closure was staircase or modified staircase technique. Cheek
      advancement flaps were used for upper lip defect closure. Inferiorly based
      nasolabial rotational flap, cheek rotational flap and modified Webster flap were
      also employed. In one patient Webster flap and unilateral staircase technique
      were combined. RESULTS: In all patients the tumor was removed completely with
      preservation of function and aesthetics. No local recurrence was observed after a
      median follow-up of 4.9 years. CONCLUSION: Perioral reconstruction after removal
      of large NMSC is a complex issue. The age group of over 70 years, frequently with
      comorbidities, requires a robust surgical technique with short operation times
      and tailored approaches for defect closure.

PMID- 25621091
TI  - Idiopathic hypereosinophilic syndrome: a rare cause of erythroderma.
AB  - BACKGROUND: Idiopathic hypereosinophilic syndrome (HES) is a rare and potentially
      lethal disorder characterized by persistently elevated eosinophil counts without
      any underlying causes. Two variants, the myeloproliferative and lymphocytic
      hypereosinophilic syndrome, have been identified. The symptoms are variable and
      related to the organs involved (cardiovascular system, skin, central and
      peripheral nervous system, gastrointestinal tract, eyes). Skin lesions can be the
      dominating and/or presenting symptom in about 50% of patients. MAIN OBSERVATIONS:
      We describe a 54-year-old man with a 12-year history of skin lesions, clinically
      consistent with psoriasis and psoriatic erythroderma. The patient was treated
      with methotrexate with no response. He experienced intense pruritus, dry/coarse
      skin and palmoplantar hyperkeratosis. Histopathology showed spongiotic dermatitis
      with no epidermotropism. Inflammatory infiltrates in upper dermis consisted
      predominantly of lymphocytes and eosinophils. Peripheral and tissue eosinophilia,
      immunophenotyping, and results of FIP1L1-PDGFRA gene analysis were suggestive of
      lymphocytic HES. The patient was treated with hydroxycarbamide (1 g/day),
      prednisolone (40 mg/day) and antihistamines with improvement. CONCLUSIONS: HES
      requires early treatment to prevent severe damage of targeted organs. The
      pleomorphic dermatological manifestations may delay the diagnosis. This case
      shows the importance of wide differential diagnosis of erythroderma. In this
      article we discuss the diagnostic criteria, the recommended work-up and
      management of idiopathic hypereosinophilic syndrome variants.

PMID- 25621092
TI  - Dermoscopy of multiple radiation-induced basal cell carcinomas in a patient
      treated previously for pinealoma.
AB  - BACKGROUND: Malignancies secondary to radiation, such as radiation-induced skin
      cancer, are possible consequences of radiation therapy. The most frequent post
      radiation skin neoplasm is basal cell carcinoma. MAIN OBSERVATION: We report a
      case of a 49-year-old woman who underwent multiple radiotherapy sessions for
      pinealoma and developed post-radiation alopecia. After 26 years the patient
      noticed the emergence of eighteen superficial scalp lesions in the previously
      irradiated areas. Dermoscopy showed predominance of ovoid nests and presence of
      arborizing vessels on pink background, consistent with basal cells carcinoma. The
      diagnosis was confirmed by histopathology. CONCLUSIONS: There is an absolute need
      to guide patients through the possible late adverse events of radiotherapy.
      Regular dermoscopy examinations should be performed, especially in areas
      previously exposed to radiation.

PMID- 25621093
TI  - Photoletter to the editor: Diffuse capillary malformation with overgrowth: a new
      and unusual case of a recent entity.
AB  - Diffuse capillary malformation with overgrowth (DCMO) has recently been proposed
      as an independent entity within the wide spectrum of vascular abnormalities
      associated with overgrowth. We present a new case of DCMO with an unusual
      harlequin-like appearance. Physicians should bear in mind this diagnosis because
      its better prognosis. 

PMID- 25621094
TI  - Photoletter to the editor: Acquired idiopathic generalized anhidrosis.
AB  - Anhidrosis is a failure in sweat production in response to physiological thermal
      or chemical stimuli. Acquired idiopathic generalized anhidrosis is a rare
      disorder without sweat gland pathology and without neurologic symptoms. Most
      cases have been reported from Far East. We report a case of a 58-year-old
      Caucasian male who suffered from heat intolerance, heat-induced cutaneous burning
      and failed to sweat even in sauna for five years. A skin biopsy disclosed no
      pathologies. He had no neurologic disorders. The diagnosis of acquired idiopathic
      generalized anhidrosis was confirmed and treatment with methylprednisolone
      initiated. This led to improvement of heat tolerance, remission of burning and
      partial remission of sweating. 

PMID- 25621095
TI  - Factors associated with repeated refusal to participate in longitudinal
      population-based HIV surveillance in rural South Africa: an observational study,
      regression analyses.
AB  - BACKGROUND: For many estimation purposes, individuals who repeatedly refuse to
      participate in longitudinal HIV surveillance pose a bigger threat to valid
      inferences than individuals who participate at least occasionally. We investigate
      the determinants of repeated refusal to consent to HIV testing in a population
      based longitudinal surveillance in rural South Africa. METHODS: We used data from
      two years (2005 & 2006) of the annual HIV surveillance conducted by the Africa
      Centre for Health and Population Studies, linking the HIV surveillance data to
      demographic and socioeconomic data. The outcome for the analysis was "repeated
      refusal". Demographic variables included sex, age, highest educational
      attainment, and place of residence. We also included a measure of wealth and the
      variable "ever had sex". To compare the association of each variable with the
      outcome, unadjusted odds ratios and standard errors were estimated. Multivariable
      logistic regression was used to estimate adjusted odds ratios and their standard
      errors. Data were analyzed using STATA 10.0. RESULTS: Of 15,557 eligible
      individuals, 46% refused to test for HIV in both rounds. Males were significantly
      more likely than females to repeatedly refuse testing. Holding all other
      variables constant, individuals in the middle age groups were more likely to
      repeatedly refuse testing compared with younger and older age groups. The odds of
      repeated refusal increased with increasing level of education and relative
      wealth. People living in urban areas were significantly more likely to repeatedly
      refuse an HIV test than people living in peri-urban or rural areas. Compared to
      those who had ever had sex, both males and females who had not yet had sex were
      significantly more likely to refuse to participate. CONCLUSIONS: The likelihood
      of repeated refusal to test for HIV in this longitudinal surveillance increases
      with education, wealth, urbanization, and primary sexual abstinence. Since the
      factors determining repeated HIV testing refusal are likely associated with HIV
      status, it is critical that selection effects are controlled for in the analysis
      of HIV surveillance data. Interventions to increase consent to HIV testing should
      consider targeting the relatively well educated and wealthy, people in urban
      areas, and individuals who have not yet sexually debuted.

PMID- 25621096
TI  - Using the Localized Surface Plasmon Resonance of Gold Nanoparticles to Monitor
      Lipid Membrane Assembly and Protein Binding.
AB  - Gold nanoparticles provide a template for preparing supported lipid layers with
      well-defined curvature. Here, we utilize the localized surface plasmon resonance
      (LSPR) of gold nanoparticles as a sensor for monitoring the preparation of lipid
      layers on nanoparticles. The LSPR is very sensitive to the immediate surroundings
      of the nanoparticle surface and it is used to monitor the coating of lipids and
      subsequent conversion of a supported bilayer to a hybrid membrane with an outer
      lipid leaflet and an inner leaflet containing hydrophobic alkanethiol. We
      demonstrate that both decanethiol and propanethiol are able to form hybrid
      membranes and that the membrane created over the shorter thiol can be stripped
      from the gold along with the lipid leaflet using beta-mercaptoethanol. The
      sensitivity of the nanoparticle LSPR to the refractive index (RI) of its
      surroundings is greater when the shorter thiol is used (37.8 +/- 1.5 nm per RI
      unit) than when the longer thiol is used (27.5 +/- 0.5 nm per RI unit). Finally,
      C-reactive protein binding to the membrane is measured using this sensor allowing
      observation of both protein-membrane and nanoparticle-nanoparticle interactions
      without chemical labeling of protein or lipids.

PMID- 25621097
TI  - A Large-Scale Study of Specific Reading Comprehension Disability.

PMID- 25621098
TI  - Rates of DSM-IV-TR Trauma Exposure and Posttraumatic Stress Disorder Among Newly
      Matriculated College Students.
AB  - The negotiation of the freedoms and responsibilities introduced as adolescents
      begin college may be particularly challenging for those with a trauma history and
      traumatic stress sequelae (posttraumatic stress disorder; PTSD). The present
      study examined the prevalence of and risk for trauma and PTSD in a large sample
      of college students. Matriculating students (N = 3,014; 1,763 female, 1,251 male)
      at two U.S. universities completed online and paper assessments. Sixty-six
      percent reported exposure to a Criterion A trauma. Nine percent met criteria for
      PTSD. Female gender was a risk factor for trauma exposure. Gender and
      socioeconomic status (SES) were associated with trauma severity. Although in
      bivariate models, gender and SES were associated with PTSD, multivariate analyses
      suggested this risk was a function of trauma severity. Thus, students enter
      college with significant trauma histories and PTSD symptoms. Findings highlight
      the potential for outreach to incoming students with trauma and point to research
      directions to enhance understanding of the psychological needs of entering
      college students.

PMID- 25621099
TI  - Shared governance in building community capacity: A case study of sleep apnea.
AB  - East Harlem has the highest diabetes mortality rate in New York City, NY. Using
      Community Based Participatory Research principles, the East Harlem Partnership
      for Diabetes Prevention-a community- academic partnership-formed to build
      community capacity with a goal to address health disparities in East Harlem. As
      part of prevention efforts, community partners chose to study the prevalence of
      obstructive sleep apnea and its relationship to pre-diabetes and progression to
      diabetes. However, community partners insisted any study of sleep apnea go beyond
      simple assessment to ensure the largely uninsured, minority population enrolled
      also have access to state of the art diagnosis and treatment. Through compromise
      and collaboration, the partnership developed a culturally appropriate and
      scientifically rigorous method to diagnose and treat sleep apnea as part of a
      novel research program.

PMID- 25621100
TI  - Management of Osteoarthritis with Avocado/Soybean Unsaponifiables.
AB  - Osteoarthritis (OA) is a painful and life-altering disease that severely limits
      the daily activity of millions of Americans, and is one of the most common causes
      of disability in the world. With obesity on the rise and the world's population
      living longer, the prevalence of OA is expected to increase dramatically in the
      coming decades, generating burdensome socioeconomic costs. This review summarizes
      current pharmaceutical, non-pharmaceutical, and prospective new treatments for
      OA, with primary focus on the dietary supplement Avocado/Soybean Unsaponifiables
      (ASU). ASU modulates OA pathogenesis by inhibiting a number of molecules and
      pathways implicated in OA. Anticatabolic properties prevent cartilage degradation
      by inhibiting the release and activity of matrix metalloproteinases (MMP-2,3,13)
      and increasing tissue inhibitors of these catabolic enzymes (TIMP-1). ASU also
      inhibits fibrinolysis by stimulating the expression of plasminogen activator
      inhibitor (PAI-1). Anabolic properties promote cartilage repair by stimulating
      collagen and aggrecan synthesis via inhibition of inflammatory cytokines such as
      IL1, IL6, IL8, TNF, ERK, and PGE2. Chondroprotective effects are mediated by
      correcting growth factor abnormalities, increasing TGFbeta while decreasing
      vascular endothelial growth factor (VEGF) in synovial fluid. ASU also inhibits
      cholesterol absorption and endogenous cholesterol biosynthesis, which mediate
      reactive oxygen species pathology in chondrocytes. At the clinical level, ASU
      reduces pain and stiffness while improving joint function, resulting in decreased
      dependence on analgesics.

PMID- 25621101
TI  - Alternative splicing: An important mechanism in stem cell biology.
AB  - Alternative splicing (AS) is an essential mechanism in post-transcriptional
      regulation and leads to protein diversity. It has been shown that AS is prevalent
      in metazoan genomes, and the splicing pattern is dynamically regulated in
      different tissues and cell types, including embryonic stem cells. These
      observations suggest that AS may play critical roles in stem cell biology. Since
      embryonic stem cells and induced pluripotent stem cells have the ability to give
      rise to all types of cells and tissues, they hold the promise of future cell
      based therapy. Many efforts have been devoted to understanding the mechanisms
      underlying stem cell self-renewal and differentiation. However, most of the
      studies focused on the expression of a core set of transcription factors and
      regulatory RNAs. The role of AS in stem cell differentiation was not clear.
      Recent advances in high-throughput technologies have allowed the profiling of
      dynamic splicing patterns and cis-motifs that are responsible for AS at a genome
      wide scale, and provided novel insights in a number of studies. In this review,
      we discuss some recent findings involving AS and stem cells. An emerging picture
      from these findings is that AS is integrated in the transcriptional and post
      transcriptional networks and together they control pluripotency maintenance and
      differentiation of stem cells. 

PMID- 25621103
TI  - Cancer stem cell plasticity and tumor hierarchy.
AB  - The origins of the complex process of intratumoral heterogeneity have been highly
      debated and different cellular mechanisms have been hypothesized to account for
      the diversity within a tumor. The clonal evolution and cancer stem cell (CSC)
      models have been proposed as drivers of this heterogeneity. However, the concept
      of cancer stem cell plasticity and bidirectional conversion between stem and non
      stem cells has added additional complexity to these highly studied paradigms and
      may help explain the tumor heterogeneity observed in solid tumors. The process of
      cancer stem cell plasticity in which cancer cells harbor the dynamic ability of
      shifting from a non-CSC state to a CSC state and vice versa may be modulated by
      specific microenvironmental signals and cellular interactions arising in the
      tumor niche. In addition to promoting CSC plasticity, these interactions may
      contribute to the cellular transformation of tumor cells and affect response to
      chemotherapeutic and radiation treatments by providing CSCs protection from these
      agents. Herein, we review the literature in support of this dynamic CSC state,
      discuss the effectors of plasticity, and examine their role in the development
      and treatment of cancer. 

PMID- 25621102
TI  - Augmenting peripheral nerve regeneration using stem cells: A review of current
      opinion.
AB  - Outcomes following peripheral nerve injury remain frustratingly poor. The reasons
      for this are multifactorial, although maintaining a growth permissive environment
      in the distal nerve stump following repair is arguably the most important. The
      optimal environment for axonal regeneration relies on the synthesis and release
      of many biochemical mediators that are temporally and spatially regulated with a
      high level of incompletely understood complexity. The Schwann cell (SC) has
      emerged as a key player in this process. Prolonged periods of distal nerve stump
      denervation, characteristic of large gaps and proximal injuries, have been
      associated with a reduction in SC number and ability to support regenerating
      axons. Cell based therapy offers a potential therapy for the improvement of
      outcomes following peripheral nerve reconstruction. Stem cells have the potential
      to increase the number of SCs and prolong their ability to support regeneration.
      They may also have the ability to rescue and replenish populations of
      chromatolytic and apoptotic neurons following axotomy. Finally, they can be used
      in non-physiologic ways to preserve injured tissues such as denervated muscle
      while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful
      consideration must be given to differentiation status, how stem cells are
      supported following transplantation and how they will be delivered to the site of
      injury. It is the aim of this article to review current opinions on the
      strategies of stem cell based therapy for the augmentation of peripheral nerve
      regeneration. 

PMID- 25621104
TI  - Control of stem cell fate by engineering their micro and nanoenvironment.
AB  - Stem cells are capable of long-term self-renewal and differentiation into
      specialised cell types, making them an ideal candidate for a cell source for
      regenerative medicine. The control of stem cell fate has become a major area of
      interest in the field of regenerative medicine and therapeutic intervention.
      Conventional methods of chemically inducing stem cells into specific lineages is
      being challenged by the advances in biomaterial technology, with evidence
      highlighting that material properties are capable of driving stem cell fate.
      Materials are being designed to mimic the clues stem cells receive in their in
      vivo stem cell niche including topographical and chemical instructions.
      Nanotopographical clues that mimic the extracellular matrix (ECM) in vivo have
      shown to regulate stem cell differentiation. The delivery of ECM components on
      biomaterials in the form of short peptides sequences has also proved successful
      in directing stem cell lineage. Growth factors responsible for controlling stem
      cell fate in vivo have also been delivered via biomaterials to provide clues to
      determine stem cell differentiation. An alternative approach to guide stem cells
      fate is to provide genetic clues including delivering DNA plasmids and small
      interfering RNAs via scaffolds. This review, aims to provide an overview of the
      topographical, chemical and molecular clues that biomaterials can provide to
      guide stem cell fate. The promising features and challenges of such approaches
      will be highlighted, to provide directions for future advancements in this
      exciting area of stem cell translation for regenerative medicine. 

PMID- 25621105
TI  - Current progress in use of adipose derived stem cells in peripheral nerve
      regeneration.
AB  - Unlike central nervous system neurons; those in the peripheral nervous system
      have the potential for full regeneration after injury. Following injury, recovery
      is controlled by schwann cells which replicate and modulate the subsequent immune
      response. The level of nerve recovery is strongly linked to the severity of the
      initial injury despite the significant advancements in imaging and surgical
      techniques. Multiple experimental models have been used with varying successes to
      augment the natural regenerative processes which occur following nerve injury.
      Stem cell therapy in peripheral nerve injury may be an important future
      intervention to improve the best attainable clinical results. In particular
      adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar
      to bone marrow derived stem cells, which are thought to have neurotrophic
      properties and the ability to differentiate into multiple lineages. They are
      ubiquitous within adipose tissue; they can form many structures resembling the
      mature adult peripheral nervous system. Following early in vitro work; multiple
      small and large animal in vivo models have been used in conjunction with
      conduits, autografts and allografts to successfully bridge the peripheral nerve
      gap. Some of the ADSC related neuroprotective and regenerative properties have
      been elucidated however much work remains before a model can be used successfully
      in human peripheral nerve injury (PNI). This review aims to provide a detailed
      overview of progress made in the use of ADSC in PNI, with discussion on the role
      of a tissue engineered approach for PNI repair. 

PMID- 25621106
TI  - Mesenchymal stem cell tracking in the intervertebral disc.
AB  - Low back pain is a common clinical problem, which leads to significant social,
      economic and public health costs. Intervertebral disc (IVD) degeneration is
      accepted as a common cause of low back pain. Initially, this is characterized by
      a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue
      hydration and hydrostatic pressure. Conservative management, including analgesia
      and physiotherapy often fails and surgical treatment, such as spinal fusion, is
      required. Stem cells offer an exciting possible regenerative approach to IVD
      disease. Preclinical research has demonstrated promising biochemical,
      histological and radiological results in restoring degenerate IVDs. Cell tracking
      provides an opportunity to develop an in-depth understanding of stem cell
      survival, differentiation and migration, enabling optimization of stem cell
      treatment. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing
      imaging modality with high spatial resolution, ideally suited for stem cell
      tracking. Furthermore, novel MRI sequences have the potential to quantitatively
      assess IVD disease, providing an improved method to review response to biological
      treatment. Superparamagnetic iron oxide nanoparticles have been extensively
      researched for the purpose of cell tracking. These particles are biocompatible,
      non-toxic and act as excellent MRI contrast agents. This review will explore
      recent advances and issues in stem cell tracking and molecular imaging in
      relation to the IVD. 

PMID- 25621107
TI  - In vivo imaging of endogenous neural stem cells in the adult brain.
AB  - The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian
      brain with their ability to self-renew and differentiate into functional neurons,
      astrocytes and oligodendrocytes has raised the hope for novel therapies of
      neurological diseases. Experimentally, those eNSCs can be mobilized in vivo,
      enhancing regeneration and accelerating functional recovery after, e.g., focal
      cerebral ischemia, thus constituting a most promising approach in stem cell
      research. In order to translate those current experimental approaches into a
      clinical setting in the future, non-invasive imaging methods are required to
      monitor eNSC activation in a longitudinal and intra-individual manner. As yet,
      imaging protocols to assess eNSC mobilization non-invasively in the live brain
      remain scarce, but considerable progress has been made in this field in recent
      years. This review summarizes and discusses the current imaging modalities
      suitable to monitor eNSCs in individual experimental animals over time, including
      optical imaging, magnetic resonance tomography and-spectroscopy, as well as
      positron emission tomography (PET). Special emphasis is put on the potential of
      each imaging method for a possible clinical translation, and on the specificity
      of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'
      [(18)F]fluoro-L-thymidine in particular constitutes a modality with excellent
      potential for clinical translation but low specificity; however, concomitant
      imaging of neuroinflammation is feasible and increases its specificity. The non
      invasive imaging strategies presented here allow for the exploitation of novel
      treatment strategies based upon the regenerative potential of eNSCs, and will
      help to facilitate a translation into the clinical setting. 

PMID- 25621108
TI  - Identify multiple myeloma stem cells: Utopia?
AB  - Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells
      which remains incurable despite recent advances in therapies. The presence of
      cancer stem cells (CSCs) has been demonstrated in many solid and hematologic
      tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not
      been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic
      non B cells was postulated by many groups. This review aims to focus on these
      distinct clonotypic subpopulations and on their ability to develop and sustain
      MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival
      and drug resistance thanks to the presence of normal and cancer stem cell niches.
      The niches and CSCs interact each other through adhesion molecules and the
      interplay between ligands and receptors activates stemness signaling (Hedgehog,
      Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug
      resistance that happens in three steps from the initial cancer cell homing
      microenvironment-mediated to development of microenvironment-independent drug
      resistance. In this review, we will underline all these aspects of MM CSCs. 

PMID- 25621109
TI  - Stem cells for the treatment of musculoskeletal pain.
AB  - Musculoskeletal-related pain is one of the most disabling health conditions
      affecting more than one third of the adult population worldwide. Pain from
      various mechanisms and origins is currently underdiagnosed and undertreated. The
      complexity of molecular mechanisms correlating pain and the progression of
      musculoskeletal diseases is not yet fully understood. Molecular biomarkers for
      objective evaluation and treatment follow-up are needed as a step towards
      targeted treatment of pain as a symptom or as a disease. Stem cell therapy is
      already under investigation for the treatment of different types of
      musculoskeletal-related pain. Mesenchymal stem cell-based therapies are already
      being tested in various clinical trials that use musculoskeletal system-related
      pain as the primary or secondary endpoint. Genetically engineered stem cells, as
      well as induced pluripotent stem cells, offer promising novel perspectives for
      pain treatment. It is possible that a more focused approach and reassessment of
      therapeutic goals will contribute to the overall efficacy, as well as to the
      clinical acceptance of regenerative medicine therapies. This article briefly
      describes the principal types of musculoskeletal-related pain and reviews the
      stem cell-based therapies that have been specifically designed for its treatment.

PMID- 25621110
TI  - Advances in cellular technology in the hematology field: What have we learned so
      far?
AB  - Despite the advances in the hematology field, blood transfusion-related
      iatrogenesis is still a major issue to be considered during such procedures due
      to blood antigenic incompatibility. This places pluripotent stem cells as a
      possible ally in the production of more suitable blood products. The present
      review article aims to provide a comprehensive summary of the state-of-the-art
      concerning the differentiation of both embryonic stem cells and induced
      pluripotent stem cells to hematopoietic cell lines. Here, we review the most
      recently published protocols to achieve the production of blood cells for future
      application in hemotherapy, cancer therapy and basic research. 

PMID- 25621111
TI  - Methods of induced pluripotent stem cells for clinical application.
AB  - Reprograming somatic cells using exogenetic gene expression represents a
      groundbreaking step in regenerative medicine. Induced pluripotent stem cells
      (iPSCs) are expected to yield novel therapies with the potential to solve many
      issues involving incurable diseases. In particular, applying iPSCs clinically
      holds the promise of addressing the problems of immune rejection and ethics that
      have hampered the clinical applications of embryonic stem cells. However, as iPSC
      research has progressed, new problems have emerged that need to be solved before
      the routine clinical application of iPSCs can become established. In this review,
      we discuss the current technologies and future problems of human iPSC generation
      methods for clinical use. 

PMID- 25621112
TI  - Adult human neural stem cell therapeutics: Current developmental status and
      prospect.
AB  - Over the past two decades, regenerative therapies using stem cell technologies
      have been developed for various neurological diseases. Although stem cell therapy
      is an attractive option to reverse neural tissue damage and to recover
      neurological deficits, it is still under development so as not to show
      significant treatment effects in clinical settings. In this review, we discuss
      the scientific and clinical basics of adult neural stem cells (aNSCs), and their
      current developmental status as cell therapeutics for neurological disease.
      Compared with other types of stem cells, aNSCs have clinical advantages, such as
      limited proliferation, inborn differentiation potential into functional neural
      cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in
      the isolation from the normal brain, and in the in vitro expansion, have blocked
      preclinical and clinical study using aNSCs. However, several groups have recently
      developed novel techniques to isolate and expand aNSCs from normal adult brains,
      and showed successful applications of aNSCs to neurological diseases. With new
      technologies for aNSCs and their clinical strengths, previous hurdles in stem
      cell therapies for neurological diseases could be overcome, to realize clinically
      efficacious regenerative stem cell therapeutics. 

PMID- 25621113
TI  - Epigenetic therapy of cancer stem and progenitor cells by targeting DNA
      methylation machineries.
AB  - Recent advances in stem cell biology have shed light on how normal stem and
      progenitor cells can evolve to acquire malignant characteristics during
      tumorigenesis. The cancer counterparts of normal stem and progenitor cells might
      be occurred through alterations of stem cell fates including an increase in self
      renewal capability and a decrease in differentiation and/or apoptosis. This
      oncogenic evolution of cancer stem and progenitor cells, which often associates
      with aggressive phenotypes of the tumorigenic cells, is controlled in part by
      dysregulated epigenetic mechanisms including aberrant DNA methylation leading to
      abnormal epigenetic memory. Epigenetic therapy by targeting DNA
      methyltransferases (DNMT) 1, DNMT3A and DNMT3B via 5-Azacytidine (Aza) and 5-Aza
      2'-deoxycytidine (Aza-dC) has proved to be successful toward treatment of
      hematologic neoplasms especially for patients with myelodysplastic syndrome. In
      this review, I summarize the current knowledge of mechanisms underlying the
      inhibition of DNA methylation by Aza and Aza-dC, and of their apoptotic- and
      differentiation-inducing effects on cancer stem and progenitor cells in leukemia,
      medulloblastoma, glioblastoma, neuroblastoma, prostate cancer, pancreatic cancer
      and testicular germ cell tumors. Since cancer stem and progenitor cells are
      implicated in cancer aggressiveness such as tumor formation, progression,
      metastasis and recurrence, I propose that effective therapeutic strategies might
      be achieved through eradication of cancer stem and progenitor cells by targeting
      the DNA methylation machineries to interfere their "malignant memory". 

PMID- 25621114
TI  - Perinatal stem cells: A promising cell resource for tissue engineering of
      craniofacial bone.
AB  - In facing the mounting clinical challenge and suboptimal techniques of
      craniofacial bone defects resulting from various conditions, such as congenital
      malformations, osteomyelitis, trauma and tumor resection, the ongoing research of
      regenerative medicine using stem cells and concurrent advancement in
      biotechnology have shifted the focus from surgical reconstruction to a novel stem
      cell-based tissue engineering strategy for customized and functional craniofacial
      bone regeneration. Given the unique ontogenetical and cell biological properties
      of perinatal stem cells, emerging evidence has suggested these extraembryonic
      tissue-derived stem cells to be a promising cell source for extensive use in
      regenerative medicine and tissue engineering. In this review, we summarize the
      current achievements and obstacles in stem cell-based craniofacial bone
      regeneration and subsequently we address the characteristics of various types of
      perinatal stem cells and their novel application in tissue engineering of
      craniofacial bone. We propose the promising feasibility and scope of perinatal
      stem cell-based craniofacial bone tissue engineering for future clinical
      application. 

PMID- 25621115
TI  - Stem cell therapy for retinal diseases.
AB  - In this review, we discuss about current knowledge about stem cell (SC) therapy
      in the treatment of retinal degeneration. Both human embryonic stem cell and
      induced pluripotent stem cell has been growth in culture for a long time, and
      started to be explored in the treatment of blinding conditions. The Food and Drug
      Administration, recently, has granted clinical trials using SC retinal therapy to
      treat complex disorders, as Stargardt's dystrophy, and patients with geographic
      atrophy, providing good outcomes. This study's intent is to overview the critical
      regeneration of the subretinal anatomy through retinal pigment epithelium
      transplantation, with the goal of reestablish important pathways from the retina
      to the occipital cortex of the brain, as well as the differentiation from
      pluripotent quiescent SC to adult retina, and its relationship with a primary
      retinal injury, different techniques of transplantation, management of immune
      rejection and tumorigenicity, its potential application in improving patients'
      vision, and, finally, approaching future directions and challenges for the
      treatment of several conditions. 

PMID- 25621116
TI  - Obesity and weight loss could alter the properties of adipose stem cells?
AB  - The discovery that adipose tissue represents an interesting source of multipotent
      stem cells has led to many studies exploring the clinical potential of these
      cells in cell-based therapies. Recent advances in understanding the secretory
      capacity of adipose tissue and the role of adipokines in the development of
      obesity and associated disorders have added a new dimension to the study of
      adipose tissue biology in normal and diseased states. Subcutaneous adipose tissue
      forms the interface between the clinical application of regenerative medicine and
      the establishment of the pathological condition of obesity. These two facets of
      adipose tissue should be understood as potentially related phenomena. Because of
      the functional characteristics of adipose stem cells, these cells represent a
      fundamental tool for understanding how these two facets are interconnected and
      could be important for therapeutic applications. In fact, adipose tissue stem
      cells have multiple functions in obesity related to adipogenic, angiogenic and
      secretory capacities. In addition, we have also previously described a
      predominance of larger blood vessels and an adipogenic memory in the subcutaneous
      adipose tissue after massive weight loss subsequent to bariatric surgery (ex
      obese patients). Understanding the reversibility of the behavior of adipose stem
      cells in obeses and in weight loss is relevant to both physiological studies and
      the potential use of these cells in regenerative medicine. 

PMID- 25621118
TI  - How do resident stem cells repair the damaged myocardium?
AB  - It has been a decade since the monumental discovery of resident stem cells in the
      mammalian heart, and the following studies witnessed the continuous turnover of
      cardiomyocytes and vascular cells, maintaining the homeostasis of the organ.
      Recently, the autologous administration of c-kit-positive cardiac stem cells in
      patients with ischemic heart failure has led to an incredible outcome; the left
      ventricular ejection fraction of the cell-treated group improved from 30% at the
      baseline to 38% after one year and to 42% after two years of cell injection. The
      potential underlying mechanisms, before and after cell infusion, are explored and
      discussed in this article. Some of them are related to the intrinsic property of
      the resident stem cells, such as direct differentiation, paracrine action, and
      immunomodulatory function, whereas others involve environmental factors, leading
      to cellular reverse remodeling and to the natural selection of "juvenile" cells.
      It has now been demonstrated that cardiac stem cells for therapeutic purposes can
      be prepared from tiny biopsied specimens of the failing heart as well as from
      frozen tissues, which may remarkably expand the repertoire of the strategy
      against various cardiovascular disorders, including non-ischemic cardiomyopathy
      and congenital heart diseases. Further translational investigations are needed to
      explore these possibilities. 

PMID- 25621117
TI  - Advances and challenges in the differentiation of pluripotent stem cells into
      pancreatic beta cells.
AB  - Pluripotent stem cells (PSCs) are able to differentiate into several cell types,
      including pancreatic beta cells. Differentiation of pancreatic beta cells depends
      on certain transcription factors, which function in a coordinated way during
      pancreas development. The existing protocols for in vitro differentiation produce
      pancreatic beta cells, which are not highly responsive to glucose stimulation
      except after their transplantation into immune-compromised mice and allowing
      several weeks for further differentiation to ensure the maturation of these cells
      in vivo. Thus, although the substantial improvement that has been made for the
      differentiation of induced PSCs and embryonic stem cells toward pancreatic beta
      cells, several challenges still hindering their full generation. Here, we
      summarize recent advances in the differentiation of PSCs into pancreatic beta
      cells and discuss the challenges facing their differentiation as well as the
      different applications of these potential PSC-derived beta cells. 

PMID- 25621119
TI  - Stem cells for spine surgery.
AB  - In the past few years, stem cells have become the focus of research by
      regenerative medicine professionals and tissue engineers. Embryonic stem cells,
      although capable of differentiating into cell lineages of all three germ layers,
      are limited in their utilization due to ethical issues. In contrast, the
      autologous harvest and subsequent transplantation of adult stem cells from bone
      marrow, adipose tissue or blood have been experimentally utilized in the
      treatment of a wide variety of diseases ranging from myocardial infarction to
      Alzheimer's disease. The physiologic consequences of stem cell transplantation
      and its impact on functional recovery have been studied in countless animal
      models and select clinical trials. Unfortunately, the bench to bedside
      translation of this research has been slow. Nonetheless, stem cell therapy has
      received the attention of spinal surgeons due to its potential benefits in the
      treatment of neural damage, muscle trauma, disk degeneration and its potential
      contribution to bone fusion. 

PMID- 25621121
TI  - Regulated genes in mesenchymal stem cells and gastric cancer.
AB  - AIM: To investigate the genes regulated in mesenchymal stem cells (MSCs) and
      diffuse-type gastric cancer (GC), gene expression was analyzed. METHODS: Gene
      expression of MSCs and diffuse-type GC cells were analyzed by microarray. Genes
      related to stem cells, cancer and the epithelial-mesenchymal transition (EMT)
      were extracted from human gene lists using Gene Ontology and reference
      information. Gene panels were generated, and messenger RNA gene expression in
      MSCs and diffuse-type GC cells was analyzed. Cluster analysis was performed using
      the NCSS software. RESULTS: The gene expression of regulator of G-protein
      signaling 1 (RGS1) was up-regulated in diffuse-type GC cells compared with MSCs.
      A panel of stem-cell related genes and genes involved in cancer or the EMT were
      examined. Stem-cell related genes, such as growth arrest-specific 6, musashi RNA
      binding protein 2 and hairy and enhancer of split 1 (Drosophila), NOTCH family
      genes and Notch ligands, such as delta-like 1 (Drosophila) and Jagged 2, were
      regulated. CONCLUSION: Expression of RGS1 is up-regulated, and genes related to
      stem cells and NOTCH signaling are altered in diffuse-type GC compared with MSCs.

PMID- 25621120
TI  - Early gestation chorionic villi-derived stromal cells for fetal tissue
      engineering.
AB  - AIM: To investigate the potential for early gestation placenta-derived
      mesenchymal stromal cells (PMSCs) for fetal tissue engineering. METHODS: PMSCs
      were isolated from early gestation chorionic villus tissue by explant culture.
      Chorionic villus sampling (CVS)-size tissue samples (mean = 35.93 mg) were used
      to test the feasibility of obtaining large cell numbers from CVS within a
      clinically relevant timeframe. We characterized PMSCs isolated from 6 donor
      placentas by flow cytometry immunophenotyping, multipotency assays, and through
      immunofluorescent staining. Protein secretion from PMSCs was examined using two
      cytokine array assays capable of probing for over 70 factors in total. Delivery
      vehicle compatibility of PMSCs was determined using three common scaffold
      systems: fibrin glue, collagen hydrogel, and biodegradable nanofibrous scaffolds
      made from a combination of polylactic acid (PLA) and poly(lactic-co-glycolic
      acid) (PLGA). Viral transduction of PMSCs was performed using a Luciferase-GFP
      containing lentiviral vector and efficiency of transduction was tested by
      fluorescent microscopy and flow cytometry analysis. RESULTS: We determined that
      an average of 2.09 * 10(6) (SD +/- 8.59 * 10(5)) PMSCs could be obtained from CVS
      size tissue samples within 30 d (mean = 27 d, SD +/- 2.28), indicating that
      therapeutic numbers of cells can be rapidly expanded from very limited masses of
      tissue. Immunophenotyping by flow cytometry demonstrated that PMSCs were positive
      for MSC markers CD105, CD90, CD73, CD44, and CD29, and were negative for
      hematopoietic and endothelial markers CD45, CD34, and CD31. PMSCs displayed
      trilineage differentiation capability, and were found to express developmental
      transcription factors Sox10 and Sox17 as well as neural-related structural
      proteins NFM, Nestin, and S100beta. Cytokine arrays revealed a robust and
      extensive profile of PMSC-secreted cytokines and growth factors, and detected 34
      factors with spot density values exceeding 10(3). Detected factors had widely
      diverse functions that include modulation of angiogenesis and immune response,
      cell chemotaxis, cell proliferation, blood vessel maturation and homeostasis,
      modulation of insulin-like growth factor activity, neuroprotection, extracellular
      matrix degradation and even blood coagulation. Importantly, PMSCs were also
      determined to be compatible with both biological and synthetic material-based
      delivery vehicles such as collagen and fibrin hydrogels, and biodegradable
      nanofiber scaffolds made from a combination of PLA and PLGA. Finally, we
      demonstrated that PMSCs can be efficiently transduced (> 95%) with a Luciferase
      GFP-containing lentiviral vector for future in vivo cell tracking after
      transplantation. CONCLUSION: Our findings indicate that PMSCs represent a unique
      source of cells that can be effectively utilized for in utero cell therapy and
      tissue engineering.

PMID- 25621122
TI  - Fetal vs adult mesenchymal stem cells achieve greater gene expression, but less
      osteoinduction.
AB  - AIM: To investigate adenoviral transduction in mesenchymal stem cells (MSCs) and
      effects on stemness in vitro and function as a cell therapy in vivo. METHODS:
      Bone marrow-derived adult and fetal MSC were isolated from an equine source and
      expanded in monolayer tissue culture. Polyethylenimine (PEI)-mediated
      transfection of pcDNA3-eGFP or adenoviral transduction of green fluorescent
      protein (GFP) was evaluated in fetal MSCs. Adenoviral-mediated transduction was
      chosen for subsequent experiments. All experiments were carried out at least in
      triplicate unless otherwise noted. Outcome assessment was obtained by flow
      cytometry or immunohystochemistry and included transduction efficiency, cell
      viability, stemness (i.e., cell proliferation, osteogenic and chondrogenic cell
      differentiation), and quantification of GFP expression. Fetal and adult MSCs were
      then transduced with an adenoviral vector containing the gene for the bone
      morphogenic protein 2 (BMP2). In vitro BMP2 expression was assessed by enzyme
      linked immunosorbent assay. In addition, MSC-mediated gene delivery of BMP2 was
      evaluated in vivo in an osteoinduction nude mouse quadriceps model. New bone
      formation was evaluated by microradiography and histology. RESULTS: PEI provided
      greater transfection and viability in fetal MSCs than other commercial chemical
      reagents. Adenoviral transduction efficiency was superior to PEI-mediated
      transfection of GFP in fetal MSCs (81.3% +/- 1.3% vs 35.0% +/- 1.6%, P < 0.05)
      and was similar in adult MSCs (78.1% +/- 1.9%). Adenoviral transduction provided
      significantly greater expression of GFP in fetal than adult MSCs (7.4 +/- 0.1 vs
      4.4 +/- 0.3 millions of mean fluorescence intensity units, P < 0.01) as well as
      significantly greater in vitro BMP2 expression (0.16 pg/cell-day vs 0.10 pg/cell
      day, P < 0.01). Fraction of fetal MSC GFP positive cells decreased significantly
      faster than adult MSCs (1.15% +/- 0.05% vs 11.4% +/- 2.1% GFP positive at 2 wk
      post-transduction, P < 0.05). Cell proliferation and osteogenic differentiation
      in vitro were not affected by Ad transduction in both fetal and adult MSCs, but
      fetal MSCs had reduced chondrogenic differentiation in vitro when compared to
      adult (P < 0.01). Chondrogenic differentiation was also significantly reduced in
      Ad-GFP transduced cells (P < 0.05). Ad-BMP2 transduced adult MSCs induced new
      bone formation in more thighs than Ad-BMP2 transduced fetal MSCs (83% vs 17% of
      the six treated thighs per group, P < 0.05) and resulted in increased femur
      midshaft diameter due to greater extent of periosteal new bone (1.57 +/- 0.35 mm
      vs 1.27 +/- 0.08 mm, P < 0.05). CONCLUSION: Fetal MSCs may be genetically
      manipulated ex vivo with adenoviral vectors. Nonetheless, the abbreviated
      expression of the exogenous gene may limit their applications in vivo.

PMID- 25621123
TI  - Lifetime Prevalence of Mental Disorders among Asian Americans: Nativity, Gender,
      and Sociodemographic Correlates.
AB  - This study examines lifetime prevalence estimates of mental disorders among Asian
      Americans with a focus on differences by nativity, gender, and other relevant
      sociodemographic correlates. We analyze cross-sectional data from the National
      Latino and Asian American Study (NLAAS), the first national epidemiological
      survey of Asian Americans which used a probability sample of household resident
      adults in the United States (N=2,095). US-born Asian Americans are more likely to
      experience lifetime mood disorders, substance use disorders, and any mental
      disorders compared to immigrants. Lifetime substance use disorders are more
      likely to occur among men rather than women. Nativity and gender show joint
      associations with different mental disorders: US-born women are at the greatest
      risk for any mood disorders; US-born men are at the greatest risk for any
      substance use disorders; and immigrant women are at the lowest risk for substance
      use disorders compared to all other groups. Analysis of the sociodemographic
      correlates reveals that the youngest immigrant women showed significantly higher
      rates of any mood disorder compared to other immigrant women. Additionally, among
      immigrant men, those with low household income are at a higher risk for mood
      disorders, and those who report fair/poor English proficiency have a higher
      prevalence of anxiety and mood disorders. This study provides documentation of
      prevalence differences in detailed mental health categories along salient axes of
      stratification among Asian Americans and provides a foundation for future
      research aimed at understanding the causes and correlates of mental health
      disparities.

PMID- 25621124
TI  - The Regional Geoboundarization of the Mexican Population in the United States
      through Saenzian Logic.
AB  - The population proliferation of Latinos in the U.S. has propelled them into the
      new majority-minority. Mexicans make up more than half of all Latinos/as. Social
      scientists have long known that accounting for social environment is crucial in
      deciphering how social structures interact with individual human behavior.
      Academic discourse needs to explicitly delineate the logic and best practices for
      measuring social contexts. Standardizing how contexts are geographically
      boundarized and subsequently measured could provide multilevel and spatial
      modeling researchers a more solid theoretical foundation for nesting individuals
      and measuring their environment. Context measuring standardization would make
      cross study comparisons more readily available. This project seeks to contribute
      to this endeavor by employing and advancing the "Saenzian" logic for
      regionalizing Mexican origin Latinos/as. The proposed solution applies to social
      research that uses U.S. Census Bureau microdata to investigate the Mexican
      population. By using Saenzian concepts, this study explores and proposes three
      alternatives for geographically regionalizing the Mexican population. Maps are
      utilized to present the logic for the classical, new, and clustered Saenzian
      regional classification schemes. Findings comparing the classical and new
      approach reveal that smaller geographical units reveal important insights that
      are typically hidden by large polygon conglomerations. Findings from the
      clustered analysis reveal that regions are more tightly and well defined. A
      discussion is offered in closing posing basic theoretical questions on what
      constitutes a region.

PMID- 25621125
TI  - Brave new world: Our journal has become an Open Access journal.

PMID- 25621127
TI  - Enzymatic and non-enzymatic post-translational modifications linking diabetes and
      heart disease.

PMID- 25621128
TI  - Can nerve conduction studies detect earlier and predict clinical diabetic
      neuropathy?

PMID- 25621126
TI  - Cell biology of diabetic nephropathy: Roles of endothelial cells,
      tubulointerstitial cells and podocytes.
AB  - Diabetic nephropathy is the major cause of end-stage renal failure throughout the
      world in both developed and developing countries. Diabetes affects all cell types
      of the kidney, including endothelial cells, tubulointerstitial cells, podocytes
      and mesangial cells. During the past decade, the importance of podocyte injury in
      the formation and progression of diabetic nephropathy has been established and
      emphasized. However, recent findings provide additional perspectives on
      pathogenesis of diabetic nephropathy. Glomerular endothelial damage is already
      present in the normoalbuminuric stage of the disease when podocyte injury starts.
      Genetic targeting of mice that cause endothelial injury leads to accelerated
      diabetic nephropathy. Tubulointerstitial damage, previously considered to be a
      secondary effect of glomerular protein leakage, was shown to have a primary
      significance in the progression of diabetic nephropathy. Emerging evidence
      suggests that the glomerular filtration barrier and tubulointerstitial
      compartment is a composite, dynamic entity where any injury of one cell type
      spreads to other cell types, and leads to the dysfunction of the whole apparatus.
      Accumulation of novel knowledge would provide a better understanding of the
      pathogenesis of diabetic nephropathy, and might lead to a development of a new
      therapeutic strategy for the disease. 

PMID- 25621129
TI  - Curious relationship between cognitive impairment and diabetic retinopathy.

PMID- 25621130
TI  - Nitric oxide donors rescue diabetic nephropathy through oxidative-stress-and
      nitrosative-stress-mediated Wnt signaling pathways.
AB  - AIMS/INTRODUCTION: The role of the renal nitric oxide (NO) system in the
      pathophysiology of diabetic nephropathy constitutes a very challenging and
      fertile field for future investigation. The purpose of the present study was to
      investigate whether NO donors can attenuate diabetic renal fibrosis and apoptosis
      through modulating oxidative-and nitrosative-stress, and Wnt signaling using in
      vivo diabetic models. MATERIALS AND METHODS: Diabetic rat was induced by a single
      intraperitoneal injection of streptozotocin. Rats in each group were
      intraperitoneally given 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (1 U/kg/day)
      and vehicle for 28 and 56 consecutive days. Expression of the oxidative-and
      nitrosative-stress, and Wnt signaling components were examined in kidneys from
      diabetic animals by quantitative reverse transcription polymerase chain reaction,
      western blot analysis and immunohistochemical staining. RESULTS: NO donor
      treatment significantly reduced the ratio of kidney weight to bodyweight and
      proteinuria. This treatment also significantly restored the suppressive effect of
      diabetes on urinary NO2 + NO3 levels. Immunohistochemistry showed that NO donor
      treatment significantly reduced transforming growth factor (TGF)-beta1,
      fibronectin, cleaved caspase-3 and triphosphate-biotin nick end-labeling
      expression in the glomeruli of diabetic rats. We found that diabetes promoted 8
      hydroxy-2'-deoxyguanosine, and peroxynitrite expression coincided with reduced
      endothelial NO synthase expression in glomeruli. Interestingly, NO donor
      treatment completely removed oxidative stress and nitrosative stress, and
      restored endothelial NO synthase expression in diabetic renal glomeruli.
      Immunohistomorphometry results showed that NO donor treatment significantly
      restored suppressed Wnt5a expression and beta-catenin immunoreactivities in
      glomeruli. Based on laser-captured microdissection for quantitative reverse
      transcription polymerase chain reaction, diabetes significantly increased TGF
      beta1, and fibronectin expression coincided with depressed Wnt5a expression. NO
      donor treatment reduced TGF-beta1, fibronectin activation, and the suppressing
      effect of diabetes on Wnt5a and beta-catenin expression in renal glomeruli.
      CONCLUSIONS: NO donor treatment alleviates extracellular matrix accumulation and
      apoptosis in diabetic nephropathy in vivo by not only preventing the diabetes
      mediated oxidative and nitrostative stress, but also restoring downregulation of
      endothelial NO synthase expression and Wnt/beta-catenin signaling. These findings
      suggest that modulation of NO is a viable alternative strategy for rescuing
      diabetic renal injury.

PMID- 25621131
TI  - Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic
      nephropathy through tubular injury in a mouse model of type 1 diabetes.
AB  - AIMS/INTRODUCTION: Senescence marker protein-30 (SMP30) is abundantly expressed
      in renal proximal tubule cells, but its expression decreases with age. Previous
      studies have shown that reduced SMP30 expression could contribute to aging
      associated deterioration of cellular function and tissue injury. In the present
      study, we investigated the effects of SMP30 deficiency on the pathogenesis of
      diabetic nephropathy. MATERIALS AND METHODS: Diabetes was induced using
      streptozotocin in male SMP30 knockout mice (KO) and wild-type mice at 7 weeks-of
      age. Vitamin C was added to the drinking water to prevent vitamin C deficiency in
      KO mice. The mice were killed 12 weeks after the induction of diabetes. RESULTS:
      Urinary biomarkers for proximal tubule damage were significantly increased in non
      diabetic KO mice compared with wild-type mice. Furthermore, diabetes-induced
      tubular damage was significantly exacerbated by SMP30 deletion. Morphological
      analysis showed a link between cortical tubulointerstitial fibrosis area and the
      degree of tubular damage. However, SMP30 deletion did not affect mesangial
      expansion. Tubular injury was associated with accumulation of hypoxia-inducible
      factor-1alpha and increased hypoxia-inducible factor-1alpha targeted gene
      expression. SMP30 deletion initiated oxidative stress; however, it did not
      exacerbate the oxidative stress seen in diabetic mice. In contrast, tubular
      inflammation was associated with SMP30 deletion only in diabetic mice.
      CONCLUSIONS: Based on this evidence, we concluded that SMP30 deficiency
      exacerbates proximal tubule injury in diabetic mice. Decreased SMP30 could
      contribute to the increased incidence of various chronic kidney diseases,
      including diabetic nephropathy, with age.

PMID- 25621132
TI  - Glycated hemoglobin for the diagnosis of diabetes and prediabetes: Diagnostic
      impact on obese and lean subjects, and phenotypic characterization.
AB  - AIMS/INTRODUCTION: Measurement of glycated hemoglobin (HbA1c) has been
      recommended for the diagnosis of diabetes and prediabetes. However,
      epidemiological studies have shown significant discordance between HbA1c and
      glucose-based tests. Of the factors that could influence agreement between HbA1c
      and the oral glucose tolerance test (OGTT), bodyweight has not been fully
      evaluated. The aims of the present study were to evaluate the impact of HbA1c
      criteria to diagnose diabetes and prediabetes compared with OGTT, and to examine
      HbA1c in relation to body mass index. MATERIALS AND METHODS: Two cohorts were
      studied, one from an obesity clinic (n = 592) and one from subjects undergoing
      screening for diabetes (n = 462). All underwent OGTT and HbA1c measurement.
      RESULTS: In the obese cohort, HbA1c >=6.5% (>=48 mmol/mol) showed a sensitivity
      of 69.3% for diabetes, whereas HbA1c 5.7-6.4% (39-46 mmol/mol) did not identify
      prediabetes well (sensitivity 39.1%). In the diabetes screening cohort, HbA1c had
      low sensitivities for both diabetes (39.2%) and prediabetes (53.3%). When
      participants were stratified according to body mass index class I-III, HbA1c
      agreement with the OGTT for diabetes was much higher (80%, P < 0.005) in class I
      obesity compared with class II-III obesity; whereas for prediabetes, HbA1c had a
      low sensitivity in all obesity classes. CONCLUSIONS: The agreement between HbA1c,
      fasting plasma glucose and 2-h glucose post-OGTT for the diagnosis of prediabetes
      was poor in our Italian population; whereas HbA1c >=6.5% showed a relatively good
      agreement with OGTT for the diagnosis of diabetes. For the first time, we have
      shown that obesity class influences the diagnostic performance of HbA1c.

PMID- 25621133
TI  - Impact of hemoglobin A1c-based criterion on diagnosis of prediabetes: The Korea
      National Health and Nutrition Examination Survey 2011.
AB  - To examine the impact of hemoglobin A1c (HbA1c) criterion on the diagnosis of
      prediabetes in Koreans, we analyzed nationally representative cross-sectional
      data of 5,845 Korean adults aged >=20 years from the Fifth Korea National Health
      and Nutrition Examination Survey 2011. Standardized prevalence rates of
      prediabetes in Korean adults by fasting plasma glucose (FPG; 5.6-6.9 mmol/L),
      HbA1c (5.7-6.4% [39-46 mmol/mol]), and combined criteria were 16.9, 28.4 and
      33.8%, respectively. Among the subjects with prediabetes, 16% met FPG criteria
      only, 55% met HbA1c criteria only and 29% met both criteria. Prediabetic subjects
      who met HbA1c criteria only were significantly older, more likely to be women,
      and had lower hemoglobin and serum iron concentrations, whereas those who met FPG
      criteria only had higher body mass index, waist circumference, systolic and
      diastolic blood pressure. In conclusion, introduction of HbA1c criterion markedly
      increased the prevalence of prediabetes in Koreans, and the two criteria
      identified people with different characteristics. 

PMID- 25621134
TI  - Gene-environment interaction between adiponectin gene polymorphisms and
      environmental factors on the risk of diabetic retinopathy.
AB  - AIMS/INTRODUCTION: To evaluate whether the adiponectin gene is associated with
      diabetic retinopathy (DR) risk and interaction with environmental factors
      modifies the DR risk, and to investigate the relationship between serum
      adiponectin levels and DR. MATERIALS AND METHODS: Four adiponectin polymorphisms
      were evaluated in 372 DR cases and 145 controls. Differences in environmental
      factors between cases and controls were evaluated by unconditional logistic
      regression analysis. The model-free multifactor dimensionality reduction method
      and traditional multiple regression models were applied to explore interactions
      between the polymorphisms and environmental factors. RESULTS: Using the
      Bonferroni method, we found no significant associations between four adiponectin
      polymorphisms and DR susceptibility. Multivariate logistic regression found that
      physical activity played a protective role in the progress of DR, whereas family
      history of diabetes (odds ratio 1.75) and insulin therapy (odds ratio 1.78) were
      associated with an increased risk for DR. The interaction between the C-11377 G
      (rs266729) polymorphism and insulin therapy might be associated with DR risk.
      Family history of diabetes combined with insulin therapy also increased the risk
      of DR. No adiponectin gene polymorphisms influenced the serum adiponectin levels.
      Serum adiponectin levels did not differ between the DR group and non-DR group.
      CONCLUSIONS: No significant association was identified between four adiponectin
      polymorphisms and DR susceptibility after stringent Bonferroni correction. The
      interaction between C-11377G (rs266729) polymorphism and insulin therapy, as well
      as the interaction between family history of diabetes and insulin therapy, might
      be associated with DR susceptibility.

PMID- 25621135
TI  - Association of cholesteryl ester transfer protein genotypes with paraoxonase-1
      activity, lipid profile and oxidative stress in type 2 diabetes mellitus: A study
      in San Luis, Argentina.
AB  - AIMS/INTRODUCTION: Diabetic dyslipidemia is common in type 2 diabetes. The TaqIB
      polymorphism in cholesteryl ester transfer protein (CETP; B1 and B2 alleles;
      rs708272) is associated with changes in enzyme activity and lipid concentrations.
      The aim of the present study was to assess associations of CETP genotypes with
      lipoprotein profile, oxidant/anti-oxidant status and the plasma activity of
      paraoxonase-1 (PON-1) in a population of diabetic patients living in San Luis,
      Argentina. MATERIALS AND METHODS: For oxidative stress status parameters,
      thiobarbituric acid-reactive substances (TBARS) and nitric oxide (NO) levels, and
      catalase and PON-1 activity were assessed in 40 patients with type 2 diabetes
      mellitus and 30 healthy participants. CETP polymorphism was analyzed by
      polymerase chain reaction-based methods. RESULTS: Type 2 diabetes mellitus had
      significantly higher concentrations of oxidative stress parameters: TBARS (P <
      0.0001) and catalase activity (P < 0.0001). PON-1 activity and NO levels were
      significantly lower in diabetics (P = 0.0002 and P = 0.0008, respectively). The
      CETP genotypes distribution among study groups was not significantly different.
      The B2 carriers of the TaqIB CETP polymorphism are associated with higher high
      density lipoprotein cholesterol levels and PON-1 activity in control and type 2
      diabetes mellitus patients. Linear regression analysis showed that there was a
      significant and positive correlation between the changes of PON-1 activity and
      high-density lipoprotein cholesterol levels in non-B1B1 (B2 carriers) in controls
      (r = 0.83, P < 0.0001) and diabetic patients (r = 0.39, P = 0.0003). CONCLUSIONS:
      The results of the current study show that type 2 diabetes mellitus is
      characterized by intense oxidative stress, and that the alterations observed in
      the lipoprotein profile and PON-1 activity might be related to the higher CETP
      activity in diabetic patients as a consequence of insulin resistance.

PMID- 25621136
TI  - Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in
      type 2 diabetes: A meta-analysis.
AB  - AIMS/INTRODUCTION: Recently, the use of rosiglitazone has been limited or
      withdrawn from the market as a result of cardiovascular risk. However,
      theoretically adding rosiglitazone to insulin could help insulin to decrease the
      glucose level. The present meta-analysis was designed to investigate the effect
      and safety of adding rosiglitazone to insulin therapy in type 2 diabetes.
      MATERIALS AND METHODS: We searched published and unpublished databases through to
      March 2012. Randomized controlled trials (RCTs) comparing rosiglitazone in
      combination with insulin (RSG + INS) vs insulin alone (INS) in type 2 diabetes
      with outcomes including glycated hemoglobin levels, insulin dose, lipid
      parameters, blood pressure, edema and cardiovascular adverse events were
      selected. RESULTS: Nine RCTs with durations of 24-26 weeks involving 1,916
      patients were included. The RSG + INS group showed significantly decreased
      glycated hemoglobin levels by 0.89% (P < 0.00001) with an 8.48-U reduction in
      daily insulin dose (P <0.00001). However, the risks of hypoglycemia and edema
      were more frequent in the RSG+INS group (P < 0.0001; P = 0.03, respectively).
      Total cholesterol level was significantly increased in the RSG+INS group (P <
      0.00001), but none of the high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, very low-density lipoprotein cholesterol or triglyceride
      levels were significantly different between groups. There were no significant
      differences between groups with regard to the risks of myocardial infarction,
      heart failure, cardiovascular death or all-cause death. CONCLUSIONS:
      Rosiglitazone could help type 2 diabetes patients with poorly controlled glucose
      with insulin therapy to decrease glucose levels and reduce their daily insulin
      dose, but at the cost of increased total cholesterol level, hypoglycemia and
      edema risk. Compared with insulin therapy, adding rosiglitazone to insulin did
      not increase the risks of myocardial infarction, heart failure, cardiovascular
      death or all-cause death.

PMID- 25621137
TI  - Efficacy and safety of switching to insulin glulisine from other rapid-acting
      insulin analogs in children with type 1 diabetes.
AB  - We investigated the efficacy and safety of switching to insulin glulisine (GLU)
      from other rapid-acting insulin analogs (Ra) in children with type 1 diabetes
      treated with multiple daily injections of insulin or continuous subcutaneous
      insulin infusion. A total of 26 children with type 1 diabetes were included. Ra
      in all of these patients was changed to GLU, and they were observed for a 6-month
      period after having previously finished treatment with other Ra. The mean
      glycated hemoglobin value decreased from 7.6 +/- 1.0 to 7.4 +/- 0.9% (P =
      0.0034), and mean plasma glucose values after breakfast and supper also improved
      from 183 +/- 50 to 153 +/- 32 mg/dL (P = 0.0035), and from 203 +/- 29 to 164 +/-
      23 mg/dL (P < 0.0001), respectively. Furthermore, the mean frequency of
      hypoglycemia was reduced from 7 +/- 6 to 4 +/- 4/month (P = 0.0004), while
      insulin doses and obesity degree were stable with statistically non-significant
      differences. In conclusion, switching to GLU might be a good treatment option for
      improving glycemic control in children with type 1 diabetes. 

PMID- 25621138
TI  - Ultrasound analysis of gray-scale median value of carotid plaques is a useful
      reference index for cerebro-cardiovascular events in patients with type 2
      diabetes.
AB  - AIMS/INTRODUCTION: Measurements of plaque echogenicity, the gray-scale median
      (GSM), were shown to correlate inversely with risk factors for cerebro
      cardiovascular disease (CVD). The eicosapentaenoic acid (EPA)/arachidonic acid
      (AA) ratio is a potential predictor of CVD risk. In the present study, we
      assessed the usefulness of carotid plaque GSM values and EPA/AA ratios in
      atherosclerotic diabetics. MATERIALS AND METHODS: A total of 84 type 2 diabetics
      with carotid artery plaques were enrolled. On admission, platelet aggregation and
      lipid profiles, including EPA and AA, were examined. Using ultrasound, mean
      intima media thickness and plaque score were measured in carotid arteries. Plaque
      echogenicity was evaluated using computer-assisted quantification of GSM. The
      patients were then further observed for approximately 3 years. RESULTS: Gray
      scale median was found to be a good marker of CVD events. On multivariate
      logistic regression analysis, GSM <32 and plaque score >=5 were significantly
      associated with past history and onset of CVD during the follow-up period, the
      odds ratios being 7.730 (P = 0.014) and 4.601 (P = 0.046), respectively. EPA/AA
      showed a significant correlation with GSM (P = 0.012) and high-density
      lipoprotein cholesterol (P = 0.039), and an inverse correlation with platelet
      aggregation (P = 0.046) and triglyceride (P = 0.020). Although most patients with
      CVD had both low GSM and low EPA/AA values, an association of EPA/AA with CVD
      events could not be statistically confirmed. CONCLUSIONS: The present results
      suggest the GSM value to be useful as a reference index for CVD events in high
      risk atherosclerotic diabetics. Associations of the EPA/AA ratio with known CVD
      risk factors warrant a larger and more extensive study to show the usefulness of
      this parameter.

PMID- 25621139
TI  - Role of elevated serum uric acid levels at the onset of overt nephropathy in the
      risk for renal function decline in patients with type 2 diabetes.
AB  - AIMS/INTRODUCTION: Despite the use of intensive therapies, declining renal
      function is often observed during the overt nephropathy stage of type 2 diabetes.
      We aimed at investigating the role of serum uric acid (SUA) levels at the onset
      of overt nephropathy in the risk of renal function decline in type 2 diabetes
      patients. MATERIALS AND METHODS: The present cohort study included 290 type 2
      diabetes patients who were followed from the onset of overt nephropathy. The
      relationship between SUA and declining renal function was assessed using Cox
      regression models after adjusting for known risk factors. RESULTS: Over a median
      4.8-year follow-up period, 85 patients (4.9/100 person-years) showed serum
      creatinine (Cr) doubling with a total cumulative incidence of 71.9% at 20 years
      of follow up. The highest SUA tertile resulted in significantly a higher
      incidence (7.7/100 person-years) and cumulative incidence at 20 years (85.7%)
      than the middle (3.9/100 person-years, 54.2%) and lowest (3.0/100 person-years,
      55.5%) tertiles. The univariate Cox hazard model resulted in significant risks
      for Cr doubling related to female sex, short diabetes duration, smoking and
      elevated levels of low-density lipoprotein cholesterol (LDL-c), glycated
      hemoglobin and SUA tertiles. SUA tertiles remained statistically significant in
      the multivariate model (highest vs lowest hazard ratio 2.68, 95% confidence
      interval 1.48-5.00, P = 0.0009). CONCLUSIONS: Elevated SUA levels within the
      normal range (men >6.3 mg/dL, women >5.1) at the onset of overt nephropathy
      resulted in an increased risk for declining renal function in type 2 diabetes
      patients.

PMID- 25621140
TI  - Case of aniridia with a heterozygous PAX6 mutation in which the glucagon response
      to arginine was evaluated.

PMID- 25621141
TI  - Corrigendum.

PMID- 25621143
TI  - A combined magnetic circular dichroism and density functional theory approach for
      the elucidation of electronic structure and bonding in three- and four-coordinate
      iron(II)-N-heterocyclic carbene complexes.
AB  - The combination of iron salts and N-heterocyclic carbene (NHC) ligands is a
      highly effective combination in catalysis, with observed catalytic activities
      being highly dependent on the nature of the NHC ligand. Detailed spectroscopic
      and electronic structure studies have been performed on both three- and four
      coordinate iron(II)-NHC complexes using a combined magnetic circular dichroism
      (MCD) and density functional theory (DFT) approach that provide detailed insight
      into the relative ligation properties of NHCs compared to traditional phosphine
      and amine ligands as well as the effects of NHC backbone structural variations on
      iron(II)-NHC bonding. Near-infrared MCD studies indicate that 10Dq(Td) for
      (NHC)2FeCl2 complexes is intermediate between those for comparable amine and
      phosphine complexes, demonstrating that such iron(II)-NHC and iron(II)-phosphine
      complexes are not simply analogues of one another. Theoretical studies including
      charge decomposition analysis indicate that the NHC ligands are slightly stronger
      donor ligands than phosphines but also result in significant weakening of the Fe
      Cl bonds compared to phosphine and amine ligands. The net result is significant
      differences in the d orbital energies in four-coordinate (NHC)2FeCl2 complexes
      relative to the comparable phosphine complexes, where such electronic structure
      differences are likely a significant contributing factor to the differing
      catalytic performances observed with these ligands. Furthermore, Mossbauer, MCD
      and DFT studies of the effects of NHC backbone structure variations (i.e.
      saturated, unsaturated, chlorinated) on iron-NHC bonding and electronic structure
      in both three- and four-coordinate iron(II)-NHC complexes indicate only small
      differences as a function of backbone structure, that are likely amplified at
      lower oxidation states of iron due to the resulting decrease in the energy
      separation between the occupied iron d orbitals and the unoccupied NHC pi*
      orbitals.

PMID- 25621144
TI  - Encapsulation of Pt(IV) Prodrugs within a Pt(II) Cage for Drug Delivery.
AB  - This report presents a novel strategy that facilitates delivery of multiple,
      specific payloads of Pt(IV) prodrugs using a well-defined supramolecular system.
      This delivery system comprises a hexanuclear Pt(II) cage that can host four
      Pt(IV) prodrug guest molecules. Relying on host-guest interactions between
      adamantyl units tethered to the Pt(IV) molecules and the cage, four prodrugs
      could be encapsulated within one cage. This host-guest complex, exhibiting a
      diameter of about 3 nm, has been characterized by detailed NMR spectroscopic
      measurements. Owing to the high positive charge, this nanostructure exhibits high
      cellular uptake. Upon entering cells and reacting with biological reductants such
      as ascorbic acid, the host-guest complex releases cisplatin, which leads to cell
      cycle arrest and apoptosis. The fully assembled complex displays cytotoxicity
      comparable to that of cisplatin against a panel of human cancer cells lines,
      whereas the cage or the Pt(IV) guest alone exhibit lower cytotoxicity. These
      findings indicate the potential of utilising well-defined supramolecular
      constructs for the delivery of prodrug molecules.

PMID- 25621145
TI  - Biosynthesis of fosfazinomycin is a convergent process.
AB  - Fosfazinomycin A is a phosphonate natural product in which the C-terminal
      carboxylate of a Val-Arg dipeptide is connected to methyl 2-hydroxy-2-phosphono
      acetate (Me-HPnA) via a unique hydrazide linkage. We report here that Me-HPnA is
      generated from phosphonoacetaldehyde (PnAA) in three biosynthetic steps through
      the combined action of an O-methyltransferase (FzmB) and an alpha-ketoglutarate
      (alpha-KG) dependent non-heme iron dioxygenase (FzmG). Unexpectedly, the latter
      enzyme is involved in two different steps, oxidation of the PnAA to
      phosphonoacetic acid as well as hydroxylation of methyl 2-phosphonoacetate. The N
      methyltransferase (FzmH) was able to methylate Arg-NHNH2 (3) to give Arg-NHNHMe
      (4), constituting the second segment of the fosfazinomycin molecule. Methylation
      of other putative intermediates such as desmethyl fosfazinomycin B was not
      observed. Collectively, our current data support a convergent biosynthetic
      pathway to fosfazinomycin.

PMID- 25621147
TI  - Cognitive Control and Rumination in Youth: The Importance of Emotion.
AB  - Rumination involves the tendency to passively dwell on negative emotions along
      with their meanings and consequences. Susan Nolen-Hoeksema demonstrated the role
      of rumination in the development of several forms of psychopathology and
      suggested that cognitive control may be one factor that makes some individuals
      more prone to ruminate than others. Studies with adults have consistently found
      that rumination is associated with cognitive control difficulties, especially
      related to switching and inhibiting emotional information. Because rumination
      predicts psychopathology by adolescence, the present study examined whether
      ruminating youth would show similar cognitive control difficulties. Fifty-two
      adolescents completed two tasks from the Cambridge Neuropsychological Test
      Automated Battery and reported on their depressive symptoms and tendency to
      ruminate. There was no effect of rumination on a task measuring general cognitive
      flexibility. However, rumination was associated with difficulty inhibiting
      negative information when switching from negative to positive blocks on an
      Affective Go/No-go task. Results suggest both similarities and differences
      compared to adult studies and are discussed in terms of clinical implications for
      the prevention and treatment of psychopathology.

PMID- 25621146
TI  - From dinosaurs to birds: a tail of evolution.
AB  - A particularly critical event in avian evolution was the transition from long- to
      short-tailed birds. Primitive bird tails underwent significant alteration, most
      notably reduction of the number of caudal vertebrae and fusion of the distal
      caudal vertebrae into an ossified pygostyle. These changes, among others,
      occurred over a very short evolutionary interval, which brings into focus the
      underlying mechanisms behind those changes. Despite the wealth of studies delving
      into avian evolution, virtually nothing is understood about the genetic and
      developmental events responsible for the emergence of short, fused tails. In this
      review, we summarize the current understanding of the signaling pathways and
      morphological events that contribute to tail extension and termination and
      examine how mutations affecting the genes that control these pathways might
      influence the evolution of the avian tail. To generate a list of candidate genes
      that may have been modulated in the transition to short-tailed birds, we analyzed
      a comprehensive set of mouse mutants. Interestingly, a prevalent pleiotropic
      effect of mutations that cause fused caudal vertebral bodies (as in the
      pygostyles of birds) is tail truncation. We identified 23 mutations in this
      class, and these were primarily restricted to genes involved in axial extension.
      At least half of the mutations that cause short, fused tails lie in the Notch/Wnt
      pathway of somite boundary formation or differentiation, leading to changes in
      somite number or size. Several of the mutations also cause additional bone
      fusions in the trunk skeleton, reminiscent of those observed in primitive and
      modern birds. All of our findings were correlated to the fossil record. An open
      question is whether the relatively sudden appearance of short-tailed birds in the
      fossil record could be accounted for, at least in part, by the pleiotropic
      effects generated by a relatively small number of mutational events. 

PMID- 25621148
TI  - Schistosomiasis and the pulmonary vasculature (2013 Grover Conference series).
AB  - Inflammation is associated with multiple forms of pulmonary arterial hypertension
      (PAH), including autoimmune (scleroderma) and infectious (HIV, schistosomiasis)
      etiologies. More than 200 million people worldwide are infected with Schistosoma,
      predominantly in Brazil, Africa, the Middle East, and South Asia. Schistosomiasis
      causes PAH in about 6.1% of those chronically infected and is particularly
      associated with the species Schistosoma mansoni. Treatment for schistosomiasis
      associated PAH includes antihelminthic treatment, if active infection is present
      (although associated with little immediate benefit to the pulmonary
      hypertension), and then pharmacologic treatment with targeted pulmonary vascular
      therapies, including phosphodiesterase type 5 inhibitors and endothelin receptor
      antagonists. The pathophysiological mechanism by which this parasitic infection
      causes pulmonary hypertension is unknown but is unlikely to be simple mechanical
      obstruction of the pulmonary vasculature by parasite eggs. Preexisting
      hepatosplenic disease due to Schistosoma infection is likely important because of
      portopulmonary hypertension and/or because it allows egg embolization to the lung
      by portocaval shunts. Potential immune signaling originating in the periegg
      granulomas causing the pulmonary vascular disease includes the cytokines
      interleukin (IL)-4, IL-6, IL-13, and transforming growth factor beta. Modulating
      these pathways may be possible targets for future therapy of schistosomiasis
      associated PAH specifically, and study of this disease may provide novel insights
      into other inflammatory causes of PAH. 

PMID- 25621149
TI  - Right ventricular endomyocardial fibrosis (2013 Grover Conference series).
AB  - Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown origin,
      affecting predominantly the right side of the heart. Its highest prevalence is in
      poor regions of sub-Saharan Africa, where it is usually found in children and
      adolescents. In areas where it is endemic, EMF is a major cause of heart failure
      and premature death. EMF of the right ventricle has unique clinical,
      electrocardiographic, and echocardiographic signs. Several features of advanced
      disease are not fully understood, the most striking being the presence of severe
      ascites with little or no pedal edema. Echocardiography is the main diagnostic
      tool and supports management of the disease in most patients, as it allows
      assessment of the severity and extension of endocardial fibrosis, the quality of
      the right atrioventricular valve, and the presence of intracardiac thrombi.
      Pulmonary hypertension in the setting of right EMF is related to chronic
      thromboembolism, through the chronic thrombi present in the severely enlarged
      right atrium found in advanced disease. The management of right EMF is difficult.
      Treatment of symptomatic patients should be surgical. However, as the disease is
      usually detected in late stages, with severe and advanced lesions, surgery cannot
      be performed without a very high risk of death and complications. New surgical
      approaches addressing several components of the structural cardiac abnormalities
      have been attempted, with promising results. EMF remains one of the most
      neglected diseases worldwide, and research into its pathophysiological mechanisms
      will probably improve outcomes and alter the natural history of the disease. This
      requires improvement in the health systems in areas of endemicity as well as the
      design of international collaborative research projects. 

PMID- 25621150
TI  - Congenital heart disease and pulmonary arterial hypertension in South America
      (2013 Grover Conference series).
AB  - South America is a territory of 17,819,100 km(2), where ~388 million people live
      in 13 countries. In the region, access to medical assistance (e.g., for treatment
      of cardiovascular disorders) is relatively easy in metropolitan areas but
      difficult in remote places such as the Andes and the Amazon. Altitudes up to
      ~6,700 m influence the prevalence of congenital heart disease (CHD) and pulmonary
      arterial hypertension (PAH). In tertiary centers, CHD is now treated earlier in
      life but remains an important etiology of PAH. In adolescents and adults with PAH
      assisted at institutions devoted to treatment of cardiovascular disorders, the
      relative frequency of PAH-CHD (~50%-60%) is even higher than that of idiopathic
      PAH. In one big tertiary center in Sao Paulo, Brazil, the prevalence of advanced
      PAH in children and adults with CHD is 1.2% and 4.2%, respectively. In young
      patients with cardiac septal defects (aged up to 2 years), pulmonary vascular
      abnormalities are a matter of concern in the decision about operability in 4.9%
      of cases. Access to specific PAH drugs is not uniform in South America, being
      unrealistic in remote places. In big cities, there are real possibilities for
      management of complex CHD, neonatal disorders, and even cardiac transplantation.
      Research activities have been implemented at clinical, translational, and basic
      levels. However, because of social and economic inequalities and political
      issues, access to best standards of medical care remains a problem in the region
      as a whole. 

PMID- 25621152
TI  - Bioenergetic shifts during transitions between stem cell states (2013 Grover
      Conference series).
AB  - Two defining characteristics of stem cells are their multilineage differentiation
      potential (multipotency or pluripotency) and their capacity for self-renewal.
      Growth factors are well-established regulators of stem cell differentiation and
      self renewal, but less is known about the influence of the metabolic state on
      stem cell function. Recent studies investigating cellular metabolism during the
      differentiation of adult stem cells, human embryonic stem cells (ESCs), and
      induced pluripotent stem cells have demonstrated that activation of specific
      metabolic pathways depends on the type of stem cells as well as the lineage cells
      are differentiating into and that these metabolic pathways can influence the
      differentiation process. However, some common patterns have emerged, suggesting
      that undifferentiated stem cells primarily rely on glycolysis to meet energy
      demands. Our own data indicate that undifferentiated ESCs not only exhibit a low
      mitochondrial membrane potential but also express high levels of the
      mitochondrial uncoupling protein 2 and of glutamine metabolism regulators when
      compared with differentiated cells. More importantly, interventions that target
      stem cell metabolism are able to either prevent or enhance differentiation. These
      findings suggest that the metabolic state of stem cells is not just a marker of
      their differentiation status but also plays an active role in regulating stem
      cell function. Regulatory metabolic pathways in stem cells may thus serve as
      important checkpoints that can be modulated to direct the regenerative capacity
      of stem cells. 

PMID- 25621151
TI  - Right ventricle in acute and chronic pulmonary embolism (2013 Grover Conference
      series).
AB  - Venous thromboembolism (VTE) encompasses deep-vein thrombosis and pulmonary
      embolism (PE). It is the third-most-frequent cardiovascular disease, with an
      overall annual incidence of 1-2 per 1,000 population. Chronic thromboembolic
      pulmonary hypertension (CTEPH) is regarded as a late sequela of PE, with a
      reported incidence varying between 0.1% and 9.1% of those surviving acute VTE.
      Right ventricular (RV) function is dependent on afterload. The most precise
      technique to describe RV function is invasive assessment of the RV-to-pulmonary
      vascular coupling. However, assessments of RV afterload (i.e., steady and
      pulsatile flow components and their product, the RC-time) may be useful
      hemodynamic surrogates of coupling. RV load is different in acute and chronic PE.
      In acute PE, more than 60% occlusion of the cross-sectional area of the pulmonary
      artery within a short period of time leads to abrupt hemodynamic collapse. If the
      time of occlusion is limited to ~15 seconds, significant decreases in fractional
      area change, tricuspid annulus systolic excursion, and RV free-wall deformation
      (strain) occur, with the latter showing significant postsystolic shortening.
      These changes have similarities to ischemic stunning, and they recover within
      minutes. In CTEPH, studies of pulmonary vascular resistance (PVR) and pulmonary
      arterial compliance demonstrated low RC-times that were further lowered after
      pulmonary endarterectomy (PEA). Immediate postoperative PVR was the only
      predictor of long-term survival/freedom from lung transplantation, suggesting
      that the effect of PEA on opening vascular territories to flow outweighs its
      effect on proximal stiffness. This review summarizes the current knowledge on
      vascular and intrinsic RV adaptation to VTE, including CTEPH, and the role of
      imaging. 

PMID- 25621153
TI  - Biomechanics of the right ventricle in health and disease (2013 Grover Conference
      series).
AB  - Right ventricular (RV) function is a major determinant of the symptomatology and
      outcome in pulmonary hypertension. The normal RV is a thin-walled flow generator
      able to accommodate large changes in venous return but unable to maintain flow
      output in the presence of a brisk increase in pulmonary artery pressure. The RV
      chronically exposed to pulmonary hypertension undergoes hypertrophic changes and
      an increase in contractility, allowing for preserved flow output in response to
      peripheral demand. Failure of systolic function adaptation (homeometric
      adaptation, described by Anrep's law of the heart) results in increased
      dimensions (heterometric adaptation; Starling's law of the heart), with a
      negative effect on diastolic ventricular interactions, limitation of exercise
      capacity, and vascular congestion. Ventricular function is described by pressure
      volume relationships. The gold standard of systolic function is maximum elastance
      (E max), or the maximal value of the ratio of pressure to volume. This value is
      not immediately sensitive to changes in loading conditions. The gold standard of
      afterload is arterial elastance (E a), defined by the ratio of pressure at E max
      to stroke volume. The optimal coupling of ventricular function to the arterial
      circulation occurs at an E max/E a ratio between 1.5 and 2. Patients with severe
      pulmonary hypertension present with an increased E max, a trend toward decreased
      E max/E a, and increased RV dimensions, along with progression of the pulmonary
      vascular disease, systemic factors, and left ventricular function. The molecular
      mechanisms of RV systolic failure are currently being investigated. It is
      important to refer biological findings to sound measurements of function.
      Surrogates for E max and E a are being developed through bedside imaging
      techniques. 

PMID- 25621154
TI  - The response of the pulmonary circulation and right ventricle to exercise:
      exercise-induced right ventricular dysfunction and structural remodeling in
      endurance athletes (2013 Grover Conference series).
AB  - There is unequivocal evidence that exercise results in considerable health
      benefits. These are the result of positive hormonal, metabolic, neuronal, and
      structural changes brought about by the intermittent physiological challenge of
      exercise. However, there is evolving evidence that intense exercise may place
      disproportionate physiological stress on the right ventricle (RV) and the
      pulmonary circulation. Both echocardiographic and invasive studies are consistent
      in demonstrating that pulmonary arterial pressures increase progressively with
      exercise intensity, such that the harder one exercises, the greater the load on
      the RV. This disproportionate load can result in fatigue or damage of the RV if
      the intensity and duration of exercise is sufficiently prolonged. This is
      distinctly different from the load imposed by exercise on the left ventricle
      (LV), which is moderated by a greater capacity for reductions in systemic
      afterload. Finally, given the increasing RV demand during exercise, it may be
      hypothesized that chronic exercise-induced cardiac remodeling (the so-called
      athlete's heart) may also disproportionately affect the RV. Indeed, there is
      evidence, although somewhat inconsistent, that RV volume increases may be
      relatively greater than those for the LV. Perhaps more importantly, there is a
      suggestion that chronic endurance exercise may cause electrical remodeling,
      predisposing some athletes to serious arrhythmias originating from the RV. Thus,
      a relatively consistent picture is emerging of acute stress, prolonged fatigue,
      and long-term remodeling, which all disproportionately affect the RV. Thus, we
      contend that the RV should be considered a potential Achilles' heel of the
      exercising heart. 

PMID- 25621155
TI  - The emerging role of metabolomics in the development of biomarkers for pulmonary
      hypertension and other cardiovascular diseases (2013 Grover Conference series).
AB  - The functional and prognostic significance of pulmonary hypertension (PH) is well
      established, yet our understanding of circulating peptides and metabolites that
      might mark or contribute to various forms of PH remains limited. Metabolites are
      the end result of all the regulatory complexity present in a cell, tissue, or
      organism and therefore serve as the most proximal reporters of the body's
      response to a disease process or drug therapy. This review presents the
      rationale, methodology, and preliminary findings from studies that apply
      comprehensive metabolite profiling to gain knowledge of new circulating markers
      of PH. 

PMID- 25621157
TI  - The heterogeneity of clinical practice patterns among an international cohort of
      pulmonary arterial hypertension experts.
AB  - The extent to which pulmonary arterial hypertension (PAH) experts share common
      practice patterns that are in alignment with published expert consensus
      recommendations is unknown. Our objective was to characterize the clinical
      management strategies used by an international cohort of self-identified PAH
      experts. A 32-item questionnaire composed mainly of rank order or Likert scale
      questions was distributed via the Internet (August 5, 2013, through January 20,
      2014) to four international pulmonary vascular disease organizations. The survey
      respondents (N = 105) were field experts reporting 11.6 +/- 8.7 years of PAH
      experience. Likert scale responses (1 = disagree, 7 = agree) were 3.0-5.0,
      indicating a disparity in opinions, for 78% of questions. Respondent
      (dis)agreement scores were 4.4 +/- 2.2 for use of expert recommendations to
      determine catheterization timing in PAH. For PAH patients without cardiogenic
      shock or known vasoreactivity status, the most and least preferred first-line
      therapies (1 = most preferred, 5 = least preferred) were phosphodiesterase type 5
      inhibitors (PDE-Vi) and subcutaneous prostacyclin analogues, respectively (1.4 +/
      0.8 vs. 4.0 +/- 1.1; P < 0.05). Compared with US-practicing clinicians (N = 46),
      non-US-practicing clinicians (N = 57) favored collaboration between cardiology
      and pulmonary medicine for clinical decision making (1 = disagree, 7 = agree; 3.1
      +/- 2.2 vs. 4.8 +/- 2.2; P < 0.0001) and PDE-Vi (6.5% vs. 22.4%) as first-line
      therapy for PAH patients with cardiogenic shock but were less likely to perform
      vasoreactivity testing in patients with lung disease-induced pulmonary
      hypertension (4.3 +/- 2.1 vs. 2.2 +/- 1.6; P < 0.0001). In conclusion, practice
      patterns among PAH experts diverge from consensus recommendations and differ by
      practice location, suggesting that opportunity may exist to improve care quality
      for this highly morbid cardiopulmonary disease. 

PMID- 25621156
TI  - The Robyn Barst Memorial Lecture: Differences between the fetal, newborn, and
      adult pulmonary circulations: relevance for age-specific therapies (2013 Grover
      Conference series).
AB  - Pulmonary arterial hypertension (PAH) contributes to poor outcomes in diverse
      diseases in newborns, infants, and children. Many aspects of pediatric PAH
      parallel the pathophysiology and disease courses observed in adult patients;
      however, critical maturational differences exist that contribute to distinct
      outcomes and therapeutic responses in children. In comparison with adult PAH,
      disruption of lung vascular growth and development, or angiogenesis, plays an
      especially prominent role in the pathobiology of pediatric PAH. In children,
      abnormalities of lung vascular development have consequences well beyond the
      adverse hemodynamic effects of PAH alone. The developing endothelium also plays
      critical roles in development of the distal airspace, establishing lung surface
      area for gas exchange and maintenance of lung structure throughout postnatal life
      through angiocrine signaling. Impaired functional and structural adaptations of
      the pulmonary circulation during the transition from fetal to postnatal life
      contribute significantly to poor outcomes in such disorders as persistent
      pulmonary hypertension of the newborn, congenital diaphragmatic hernia,
      bronchopulmonary dysplasia, Down syndrome, and forms of congenital heart disease.
      In addition, several studies support the hypothesis that early perinatal events
      that alter lung vascular growth or function may set the stage for increased
      susceptibility to PAH in adult patients ("fetal programming"). Thus, insights
      into basic mechanisms underlying unique features of the developing pulmonary
      circulation, especially as related to preservation of endothelial survival and
      function, may provide unique therapeutic windows and distinct strategies to
      improve short- and long-term outcomes of children with PAH. 

PMID- 25621159
TI  - Safety and efficacy of transition from inhaled treprostinil to parenteral
      treprostinil in selected patients with pulmonary arterial hypertension.
AB  - Guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend
      sequential add-on therapy for patients who deteriorate or fail to improve
      clinically. However, it is not known whether these patients also benefit from
      transitioning from inhaled prostacyclins to parenteral prostacyclins. We sought
      to characterize PAH patients receiving inhaled treprostinil who were transitioned
      to parenteral treprostinil. We conducted a multicenter retrospective study at 7
      PAH centers and collected reasons, methods, safety, and outcome of patients
      transitioned from inhaled treprostinil to parenteral treprostinil. Twenty-six
      patients with pulmonary hypertension in group 1, 4, or 5 transitioned from
      inhaled treprostinil to parenteral treprostinil (10 intravenous, 16
      subcutaneous). Twenty-four patients were also on one or two oral therapies.
      Reasons for transition were clinical deterioration, lack of clinical improvement,
      and pregnancy (19, 6, and 1 patients, respectively). Transitions occurred in
      hospital, clinic, or home (17, 7, and 2 patients, respectively). Parenteral
      infusion was started after the last inhaled treatment at maintenance dose (13
      patients), after the inhaled therapy was downtitrated to 18 [Formula: see text]g
      (6 patients), or with an overlap of inhaled downtitration with parenteral
      uptitration (7 patients). The transition was safe; side effects included symptoms
      of prostacyclin overdose. Patients were followed for 3-18 months. At 3 months, 8
      patients improved, 17 maintained their functional class, and 1 continued to
      deteriorate. In conclusion, selected PAH patients can be safely transitioned from
      inhaled treprostinil to parenteral treprostinil using a variety of methodologies
      in different settings with the expectation that patients will improve or at least
      remain clinically stable. 

PMID- 25621158
TI  - Imatinib in pulmonary arterial hypertension: c-Kit inhibition.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease characterized by
      severe remodeling of the pulmonary artery resulting in increased pulmonary artery
      pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow
      derived progenitor cells play a critical role in vascular homeostasis and have
      been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit(+)
      hematopoietic progenitors and mast cells has been noted in the remodeled vessels
      in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown
      to be beneficial for patients with PAH. Here we hypothesize that the clinical
      benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor
      cell mobilization and maturation into mast cells. As a corollary to the phase 3
      study using imatinib in PAH, blood samples were collected from 12 patients prior
      to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight
      were randomized to imatinib and 4 to placebo. Circulating c-Kit(+) and
      CD34(+)CD133(+) hematopoietic progenitors as well as biomarkers of mast cell
      numbers and activation were measured. Circulating CD34(+)CD133(+) and c-Kit(+)
      progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib
      therapy (all P < 0.05). In addition, total tryptase, a marker of mast cell load,
      dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular
      resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a
      potential mechanism of action of imatinib in PAH and suggest that tryptase is a
      potential biomarker of response to therapy. 

PMID- 25621160
TI  - Effects of tetrahydrobiopterin oral treatment in hypoxia-induced pulmonary
      hypertension in rat.
AB  - Endothelial nitric oxide synthase (eNOS) plays a major role in maintaining
      pulmonary vascular homeostasis. Tetrahydrobiopterin (BH4), an essential cofactor
      that stabilizes the dimerization of eNOS and balances nitric oxide (NO) and
      superoxide production, may have therapeutic potential in pulmonary hypertension.
      In the isolated perfused lung, we demonstrated a direct effect of exogenous
      administration of BH4 on pulmonary NO production, leading to acute vasorelaxation
      during the plateau phase of hypoxia-induced pulmonary vasoconstriction. In the
      chronic hypoxia-induced pulmonary hypertension rat model, chronic BH4 oral
      administration attenuated the pressor response to hypoxia (mean pulmonary artery
      pressure +/- standard error of the mean, 31.8 +/- 0.5 mmHg at 100 mg/kg/day;
      placebo group, 36.3 +/- 0.6 mmHg; P < 0.05). During telemetric monitoring, right
      ventricular systolic pressure was reduced by approximately 50% after 1 week of
      BH4 treatment at 100 mg/kg/day. BH4 at 100 mg/kg/day reduced right ventricular
      hypertrophy (from 0.55 +/- 0.01 to 0.50 +/- 0.01; P < 0.05) and pulmonary
      vascular muscularization (from 79.2% +/- 2% to 65.2% +/- 3%; P < 0.01). BH4
      treatment enhanced lung eNOS activity and reduced superoxide production, with a
      net increase in cyclic guanosine monophosphate levels. BH4 is effective in
      attenuating pulmonary hypertension in the hypoxic rat model when given as a
      rescue therapy. 

PMID- 25621161
TI  - Possible role of lysophosphatidic acid in rat model of hypoxic pulmonary vascular
      remodeling.
AB  - Pulmonary hypertension is characterized by cellular and structural changes in the
      vascular wall of pulmonary arteries. We hypothesized that lysophosphatidic acid
      (LPA), a bioactive lipid, is implicated in this vascular remodeling in a rat
      model of hypoxic pulmonary hypertension. Exposure of Wistar rats to 10% O2 for 3
      weeks induced an increase in the mean serum levels of LPA, to 40.9 (log
      detransformed standard deviations: 23.4-71.7) MUM versus 21.6 (11.0-42.3) MUM in
      a matched control animal group (P = 0.037). We also observed perivascular LPA
      immunohistochemical staining in lungs of hypoxic rats colocalized with the
      secreted lysophospholipase D autotaxin (ATX). Moreover, ATX colocalized with mast
      cell tryptase, suggesting implication of these cells in perivascular LPA
      production. Hypoxic rat lungs expressed more ATX transcripts (2.4-fold) and more
      transcripts of proteins implicated in cell migration: beta2 integrin (1.74-fold),
      intracellular adhesion molecule 1 (ICAM-1; 1.84-fold), and alphaM integrin (2.70
      fold). Serum from the hypoxic group of animals had significantly higher
      chemoattractant properties toward rat primary lung fibroblasts, and this increase
      in cell migration could be prevented by the LPA receptor 1 and 3 antagonists. LPA
      also increased adhesive properties of human pulmonary artery endothelial cells as
      well as those of human peripheral blood mononuclear cells, via the activation of
      LPA receptor 1 or 3 followed by the stimulation of gene expression of ICAM-1,
      beta-1, E-selectin, and vascular cell adhesion molecule integrins. In conclusion,
      chronic hypoxia increases circulating and tissue levels of LPA, which might
      induce fibroblast migration and recruitment of mononuclear cells in pulmonary
      vasculature, both of which contribute to pulmonary vascular remodeling. 

PMID- 25621162
TI  - Sickle erythrocytes and platelets augment lung leukotriene synthesis with
      downregulation of anti-inflammatory proteins: relevance in the pathology of the
      acute chest syndrome.
AB  - Initiation, progression, and resolution of vaso-occlusive pain episodes in sickle
      cell disease (SCD) have been recognized as reperfusion injury, which provokes an
      inflammatory response in the pulmonary circulation. Some 5-lipoxygenase (5-lox)
      metabolites are potent vasoconstrictors in the pulmonary circulation. We studied
      stimulation of production of the inflammatory eicosanoids leukotrienes (LTs) and
      prostaglandin E2 (PGE2) by isolated rat lungs perfused with sickle (HbSS)
      erythrocytes. Our hypothesis is that HbSS erythrocytes produce more LTs than
      normal (HbAA) erythrocytes, which can induce vaso-occlusive episodes in SCD
      patients. Lung perfusates were collected at specific time points and purified by
      high-pressure liquid chromatography, and LTC4 and PGE2 contents were measured by
      enzyme-linked immunosorbent assay (ELISA). Rat lung explants were also cultured
      with purified HbAA and HbSS peptides, and 5-lox, cyclooxygenase 1/2, and platelet
      activating factor receptor (PAFR) proteins were measured by Western blotting,
      while prostacyclin and LTs produced by cultured lung explants were measured by
      ELISA. Lung weight gain and blood gas data were not different among the groups.
      HbSS-perfused lungs produced more LTC4 and PGE2 than HbAA-perfused lungs: 10.40
      +/- 0.62 versus 0.92 +/- 0.2 ng/g dry lung weight (mean +/- SEM; P = 0.0001) for
      LTC4. Inclusion of autologous platelets (platelet-rich plasma) elevated LTC4
      production to 12.6 +/- 0.96 and 7 +/- 0.60 ng/g dry lung weight in HbSS and HbAA
      perfusates, respectively. HbSS lungs also expressed more 5-lox and PAFR. The data
      suggest that HbSS erythrocytes and activated platelets in patient's pulmonary
      microcirculation will enhance the synthesis and release of the proinflammatory
      mediators LTC4 and PGE2, both of which may contribute to onset of the acute chest
      syndrome in SCD. 

PMID- 25621163
TI  - Myosin heavy chain 15 is associated with bovine pulmonary arterial pressure.
AB  - Bovine pulmonary hypertension, brisket disease, causes significant morbidity and
      mortality at elevations above 2,000 m. Mean pulmonary arterial pressure (mPAP) is
      moderately heritable, with inheritance estimated to lie within a few major genes.
      Invasive mPAP measurement is currently the only tool available to identify cattle
      at risk of hypoxia-induced pulmonary hypertension. A genetic test could allow
      selection of cattle suitable for high altitude without the need for invasive
      testing. In this study we evaluated three candidate genes (myosin heavy chain 15
      [MYH15], NADH dehydrogenase flavoprotein 2, and FK binding protein 1A) for
      association with mPAP in 166 yearling Angus bulls grazing at 2,182 m. The T
      allele (rs29016420) of MYH15 was linked to lower mPAP in a dominant manner (CC
      47.2 +/- 1.6 mmHg [mean +/- standard error of the mean]; CT/TT 42.8 +/- 0.7 mmHg;
      P = 0.02). The proportions of cattle with MYH15 CC, CT, and TT genotypes were
      55%, 41%, and 4%, respectively. Given the high frequency of the deleterious
      allele, it is likely that the relative contribution of MYH15 polymorphisms to
      pulmonary hypertension is small, supporting previous predictions that the disease
      is polygenic. We evaluated allelic frequency of MYH15 in the Himalayan yak (Bos
      grunniens), a closely related species adapted to high altitude, and found 100%
      prevalence of T allele homozygosity. In summary, we identified a polymorphism in
      MYH15 significantly associated with mPAP. This finding may aid selection of
      cattle suitable for high altitude and contribute to understanding human hypoxia
      induced pulmonary hypertension. 

PMID- 25621164
TI  - Physician attitudes toward palliative care for patients with pulmonary arterial
      hypertension: results of a cross-sectional survey.
AB  - Pulmonary arterial hypertension (PAH) is a chronic, symptomatic, life-threatening
      illness; however, it is complex, with variable expression regarding impact on
      quality of life (QOL). This study investigated attitudes and comfort of
      physicians regarding palliative care (PC) for patients with PAH and explored
      potential barriers to PC in PAH. An internet-based, mixed-methods survey was
      distributed to Pulmonary Hypertension Clinicians and Researchers, a professional
      organization within the Pulmonary Hypertension Association. Only responses from
      physicians involved in clinical care of patients with PAH were analyzed. Of 355
      clinicians/researchers, 79 (22%) returned surveys, including 76 (21%) providers
      involved in clinical care. Responding physicians were mainly pulmonologists
      (67%), practiced in university/academic medical centers (89%), had been in
      practice a mean of 12 +/- 7 years, cared for a median of 100 PAH patients per
      year, and reported a high level of confidence in managing PAH (87%), advanced PAH
      specific pharmacologic interventions (95%), and end-of-life care (88%). Smaller
      proportions were comfortable managing pain (62%) and QOL issues (78%). Most
      physicians (91%) reported utilizing PC consultation at least once in the prior
      year, primarily in the setting of end-of-life/active dying (59%), hospice
      referral (46%), or symptomatic dyspnea/impaired QOL (40%). The most frequent
      reasons for not referring patients to PC included nonapproval by the
      patient/family (51%) and concern that PC is "giving up hope" (43%). PAH may
      result in symptoms that impair QOL despite optimal PAH therapy; however, PC
      awareness and utilization for PAH providers is low. Opportunities may exist to
      integrate PC into care for PAH patients. 

PMID- 25621165
TI  - Acute effects of levosimendan in experimental models of right ventricular
      hypertrophy and failure.
AB  - Pulmonary arterial hypertension (PAH) is a fatal disease, and the ultimate cause
      of death is right ventricular (RV) failure. In this study, we investigated the
      acute hemodynamic effects of levosimendan in two rat models of RV hypertrophy and
      failure. Wistar rats were randomized to receive sham surgery (n = 8), pulmonary
      trunk banding (PTB; n = 8), or monocrotaline injection (MCT; n = 7). RV function
      was evaluated at baseline and after injection of placebo and two concentrations
      of levosimendan (12 and 60 MUg/kg) using magnetic resonance imaging,
      echocardiography, and invasive pressure recordings. PTB and MCT injection caused
      hypertrophy, dilatation, and failure of the RV compared with sham surgery.
      Levosimendan increased RV end systolic pressure (sham surgery: 16.0% +/- 3.8% [P
      = 0.0038]; MCT: 9.9% +/- 3.1% [P = 0.018]; PTB: 24.5% +/- 3.3% [P = 0.0001]; mean
      +/- SEM) compared with placebo. Levosimendan markedly increased RV stroke volume
      (SV) in the MCT group (29.1% +/- 8.3%; P = 0.012), did not change RV SV in the
      PTB group (0.4% +/- 4.5%; P = 0.93), and decreased RV SV in the sham surgery
      group (-10.9% +/- 3.7%; P = 0.020). Nitroprusside, which was used to mimic the
      systemic arterial vasodilator action of levosimendan, did not influence RV
      function. These data demonstrate that levosimendan acutely improves the failing
      right heart in a MCT model of PAH and that the mechanism involves a direct acute
      positive inotropic effect on the hypertrophic and failing RV of the rat. 

PMID- 25621166
TI  - Pulmonary arterial hypertension in a patient with beta-thalassemia intermedia and
      reversal with infusion epoprostenol then transition to oral calcium channel
      blocker therapy: review of literature.
AB  - Pulmonary arterial hypertension (PAH) is a potentially life-threatening
      complication of thalassemia. A sexagenarian with beta-thalassemia intermedia
      presented with new-onset dyspnea and syncope. Right heart catheterization
      confirmed severe PAH. Her functional class IV symptoms and severely elevated mean
      pulmonary artery pressure prompted the initiation of continuous epoprostenol
      therapy. Clinical follow-up documented significant improvement in functional
      class, 6-minute walk distance, and right ventricular size and function as well as
      pulmonary arterial pressure on echocardiogram. At the patient's request,
      epoprostenol was down-titrated and eventually discontinued. The patient was then
      safely transitioned to nifedipine therapy after verification of
      vasoresponsiveness. 

PMID- 25621167
TI  - Aligning 3D nanofibrous networks from self-assembled phenylalanine nanofibers.
AB  - Self-assembled synthetic materials are typically disordered, and controlling the
      alignment of such materials at the nanometer scale may be important for a variety
      of biological applications. In this study, we have applied directional freeze
      drying, for the first time, to develop well aligned three dimensional (3D)
      nanofibrous materials using amino acid like L-phenylalanine (Phe). 3D free
      standing Phe nanofibrous monoliths have been successfully prepared using
      directional freeze-drying, and have presented a unique hierarchical structure
      with well-aligned nanofibers at the nanometer scale and an ordered compartmental
      architecture at the micrometer scale. We have found that the physical properties
      (e.g. nanofiber density and alignment) of the nanofibrous materials could be
      tuned by controlling the concentration and pH of the Phe solution and the
      freezing temperature. Moreover, the same strategy (i.e. directional freeze
      drying) has been successfully applied to assemble peptide nanofibrous materials
      using a dipeptide (i.e. diphenylalanine), and to assemble Phe-based nanofibrous
      composites using polyethylenimine and poly(vinyl alcohol). The tunability of the
      nanofibrous structures together with the biocompatibility of Phe may make these
      3D nanofibrous materials suitable for a variety of applications, including
      biosensor templates, tissue scaffolds, filtration membranes, and absorbents. The
      strategy reported here is likely applicable to create aligned nanofibrous
      structures using other amino acids, peptides, and polymers.

PMID- 25621168
TI  - Structural hysteresis in dragline spider silks induced by supercontraction: An x
      ray fiber micro-diffraction study.
AB  - Interaction with water causes shrinkage and significant changes in the structure
      of spider dragline silks, which has been referred to as supercontraction in the
      literature. Preferred orientation or alignment of protein chains with respect to
      the fiber axis is extensively changed during this supercontraction process.
      Synchrotron x-ray micro-fiber diffraction experiments have been performed on
      Nephila clavipes and Argiope aurantia major and minor ampullate dragline spider
      fibers in the native dry, contracted (by immersion in water) and restretched
      (from contracted) states. Changes in the orientation of beta-sheet
      nanocrystallites and the oriented component of the amorphous network have been
      determined from wide-angle x-ray diffraction patterns. While both the crystalline
      and amorphous components lose preferred orientation on wetting with water, the
      nano-crystallites regain their orientation on wet-restretching, whereas the
      oriented amorphous components only partially regain their orientation. Dragline
      major ampullate silks in both the species contract more than their minor
      ampullate silks.

PMID- 25621169
TI  - The secreted protein S100A7 (psoriasin) is induced by telomere dysfunction in
      human keratinocytes independently of a DNA damage response and cell cycle
      regulators.
AB  - BACKGROUND: Replicative senescence is preceded by loss of repeat sequences of DNA
      from the telomeres that eventually leads to telomere dysfunction, the
      accumulation of irreparable DNA double strand breaks and a DNA damage response
      (DDR). However, we have previously reported that whilst telomere dysfunction in
      human keratinocytes is associated with a permanent cell cycle arrest, the DDR was
      very weak and transcriptional profiling also revealed several molecules normally
      associated with keratinocytes terminal differentiation, including S100A7
      (psoriasin). RESULTS: We show here that S100A7 and the closely related S100A15
      (koebnerisin) are not induced by repairable or irreparable DSBs, ruling out the
      hypotheses that these genes are induced either by the low DDR observed or by non
      specific cell cycle arrest. We next tested whether S100A7 was induced by the cell
      cycle effectors ARF (p14(ARF)), CDKN2A (p16(INK4A)) and TP53 (p53) and found
      that, although all induced a similar level of acute and permanent cell cycle
      arrest to telomere dysfunction, none induced S100A7 (except p53 over-expression
      at high levels), showing that cell cycle arrest is not sufficient for its
      induction. The closely related transcript S100A15 was also upregulated by
      telomere dysfunction, to a similar extent by p16(INK4A) and p53 and to a lesser
      extent by p14(ARF). CONCLUSIONS: Our results show that mere cell cycle arrest,
      the upregulation of senescence-associated cell cycle effectors and DNA damage are
      not sufficient for the induction of the S100 transcripts; they further suggest
      that whilst the induction of S100A15 expression is linked to both telomere
      dependent and -independent senescence, S100A7 expression is specifically
      associated with telomere-dependent senescence in normal keratinocytes. As both
      S100A7 and S100A15 are secreted proteins, they may find utility in the early
      detection of human keratinocyte telomere dysfunction and senescence.

PMID- 25621171
TI  - VizBin - an application for reference-independent visualization and human
      augmented binning of metagenomic data.
AB  - BACKGROUND: Metagenomics is limited in its ability to link distinct microbial
      populations to genetic potential due to a current lack of representative isolate
      genome sequences. Reference-independent approaches, which exploit for example
      inherent genomic signatures for the clustering of metagenomic fragments
      (binning), offer the prospect to resolve and reconstruct population-level genomic
      complements without the need for prior knowledge. RESULTS: We present VizBin, a
      JavaTM-based application which offers efficient and intuitive reference
      independent visualization of metagenomic datasets from single samples for
      subsequent human-in-the-loop inspection and binning. The method is based on
      nonlinear dimension reduction of genomic signatures and exploits the superior
      pattern recognition capabilities of the human eye-brain system for cluster
      identification and delineation. We demonstrate the general applicability of
      VizBin for the analysis of metagenomic sequence data by presenting results from
      two cellulolytic microbial communities and one human-borne microbial consortium.
      The superior performance of our application compared to other analogous
      metagenomic visualization and binning methods is also presented. CONCLUSIONS:
      VizBin can be applied de novo for the visualization and subsequent binning of
      metagenomic datasets from single samples, and it can be used for the post hoc
      inspection and refinement of automatically generated bins. Due to its
      computational efficiency, it can be run on common desktop machines and enables
      the analysis of complex metagenomic datasets in a matter of minutes. The software
      implementation is available at https://claczny.github.io/VizBin under the BSD
      License (four-clause) and runs under Microsoft WindowsTM, Apple Mac OS XTM (10.7
      to 10.10), and Linux.

PMID- 25621170
TI  - On the way to commercializing plant cell culture platform for biopharmaceuticals:
      present status and prospect.
AB  - Plant cell culture is emerging as an alternative bioproduction system for
      recombinant pharmaceuticals. Growing plant cells in vitro under controlled
      environmental conditions allows for precise control over cell growth and protein
      production, batch-to-batch product consistency and a production process aligned
      with current good manufacturing practices. With the recent US FDA approval and
      commercialization of the world's first plant cell-based recombinant
      pharmaceutical for human use, beta-glucocerebrosidase for treatment of Gaucher's
      disease, a new era has come in which plant cell culture shows high potential to
      displace some established platform technologies in niche markets. This review
      updates the progress in plant cell culture processing technology, highlights
      recent commercial successes and discusses the challenges that must be overcome to
      make this platform commercially viable.

PMID- 25621174
TI  - Objectively Measured Sleep and beta-amyloid Burden in Older Adults: A Pilot
      Study.
AB  - BACKGROUND/AIMS: Although disturbed sleep is associated with cognitive deficits,
      the association between sleep disturbance and Alzheimer's disease (AD) pathology
      is unclear. In this pilot study, we examined the extent to which sleep duration,
      sleep quality, and sleep-disordered breathing (SDB) are associated with beta
      amyloid (Abeta) deposition in the brains of living humans. METHODS: We studied 13
      older adults (8 with normal cognition and 5 with mild cognitive impairment
      (MCI)). Participants completed neuropsychological testing, polysomnography and
      Abeta imaging with [11C]-Pittsburgh compound B. RESULTS: Among participants with
      MCI, higher apnea-hypopnea index and oxygen desaturation index were associated
      with greater Abeta deposition, globally and regionally in the precuneus. There
      were no significant associations between SDB and Abeta deposition among
      cognitively normal participants. There were no significant associations between
      sleep duration or sleep fragmentation and Abeta deposition. CONCLUSION: These
      preliminary results suggest that, among older adults with MCI, greater SDB
      severity is associated with greater Abeta deposition.

PMID- 25621173
TI  - Mitochondria as biosynthetic factories for cancer proliferation.
AB  - Unchecked growth and proliferation is a hallmark of cancer, and numerous
      oncogenic mutations reprogram cellular metabolism to fuel these processes. As a
      central metabolic organelle, mitochondria execute critical biochemical functions
      for the synthesis of fundamental cellular components, including fatty acids,
      amino acids, and nucleotides. Despite the extensive interest in the glycolytic
      phenotype of many cancer cells, tumors contain fully functional mitochondria that
      support proliferation and survival. Furthermore, tumor cells commonly increase
      flux through one or more mitochondrial pathways, and pharmacological inhibition
      of mitochondrial metabolism is emerging as a potential therapeutic strategy in
      some cancers. Here, we review the biosynthetic roles of mitochondrial metabolism
      in tumors and highlight specific cancers where these processes are activated. 

PMID- 25621175
TI  - Quantitative assessment of inhalation exposure and deposited dose of aerosol from
      nanotechnology-based consumer sprays.
AB  - This study provides a quantitative assessment of inhalation exposure and
      deposited aerosol dose in the 14 nm to 20 MUm particle size range based on the
      aerosol measurements conducted during realistic usage simulation of five
      nanotechnology-based and five regular spray products matching the nano-products
      by purpose of application. The products were also examined using transmission
      electron microscopy. In seven out of ten sprays, the highest inhalation exposure
      was observed for the coarse (2.5-10 MUm) particles while being minimal or below
      the detection limit for the remaining three sprays. Nanosized aerosol particles
      (14-100 nm) were released, which resulted in low but measurable inhalation
      exposures from all of the investigated consumer sprays. Eight out of ten products
      produced high total deposited aerosol doses on the order of 101-103 ng kg-1 bw
      per application, ~85-88% of which were in the head airways, only <10% in the
      alveolar region and <8% in the tracheobronchial region. One nano and one regular
      spray produced substantially lower total deposited doses (by 2-4 orders of
      magnitude less), only ~52-64% of which were in the head while ~29-40% in the
      alveolar region. The electron microscopy data showed nanosized objects in some
      products not labeled as nanotechnology-based and conversely did not find nano
      objects in some nano-sprays. We found no correlation between nano-object presence
      and abundance as per the electron microscopy data and the determined inhalation
      exposures and deposited doses. The findings of this study and the reported
      quantitative exposure data will be valuable for the manufacturers of
      nanotechnology-based consumer sprays to minimize inhalation exposure from their
      products, as well as for the regulators focusing on protecting the public health.

PMID- 25621172
TI  - Putting the pieces together: How is the mitochondrial pathway of apoptosis
      regulated in cancer and chemotherapy?
AB  - In order to solve a jigsaw puzzle, one must first have the complete picture to
      logically connect the pieces. However, in cancer biology, we are still gaining an
      understanding of all the signaling pathways that promote tumorigenesis and how
      these pathways can be pharmacologically manipulated by conventional and targeted
      therapies. Despite not having complete knowledge of the mechanisms that cause
      cancer, the signaling networks responsible for cancer are becoming clearer, and
      this information is serving as a solid foundation for the development of
      rationally designed therapies. One goal of chemotherapy is to induce cancer cell
      death through the mitochondrial pathway of apoptosis. Within this review, we
      present the pathways that govern the cellular decision to undergo apoptosis as
      three distinct, yet connected puzzle pieces: (1) How do oncogene and tumor
      suppressor pathways regulate apoptosis upstream of mitochondria? (2) How does the
      B-cell lymphoma 2 (BCL-2) family influence tumorigenesis and chemotherapeutic
      responses? (3) How is post-mitochondrial outer membrane permeabilization (MOMP)
      regulation of cell death relevant in cancer? When these pieces are united, it is
      possible to appreciate how cancer signaling directly impacts upon the fundamental
      cellular mechanisms of apoptosis and potentially reveals novel pharmacological
      targets within these pathways that may enhance chemotherapeutic success. 

PMID- 25621176
TI  - No consistent association between processes-of-care and health-related quality of
      life among patients with diabetes: a missing link?
AB  - PURPOSE: Health-related quality of life (HRQoL) is considered a representative
      outcome in the evaluation of chronic disease management initiatives emphasizing
      patient-centered care. We evaluated the association between receipt of processes
      of-care (PoC) for diabetes and HRQoL. METHODS: This cross-sectional study used
      self-reported data from non-institutionalized adults with diabetes in a Swiss
      canton. Outcomes were the physical/mental composites of the short form health
      survey 12 (SF-12) physical composite score, mental composite score (PCS, MCS) and
      the Audit of Diabetes-Dependent Quality of Life (ADDQoL). Main exposure variables
      were receipt of six PoC for diabetes in the past 12 months, and the Patient
      Assessment of Chronic Illness Care (PACIC) score. We performed linear regressions
      to examine the association between PoC, PACIC and the three composites of HRQoL.
      RESULTS: Mean age of the 519 patients was 64.5 years (SD 11.3); 60% were male,
      87% reported type 2 or undetermined diabetes and 48% had diabetes for over 10
      years. Mean HRQoL scores were SF-12 PCS: 43.4 (SD 10.5), SF-12 MCS: 47.0 (SD
      11.2) and ADDQoL: -1.6 (SD 1.6). In adjusted models including all six PoC
      simultaneously, receipt of influenza vaccine was associated with lower ADDQoL
      (beta=-0.4, p<=0.01) and foot examination was negatively associated with SF-12
      PCS (beta=-1.8, p<=0.05). There was no association or trend towards a negative
      association when these PoC were reported as combined measures. PACIC score was
      associated only with the SF-12 MCS (beta=1.6, p<=0.05). CONCLUSIONS: PoC for
      diabetes did not show a consistent association with HRQoL in a cross-sectional
      analysis. This may represent an effect lag time between time of process received
      and health-related quality of life. Further research is needed to study this
      complex phenomenon.

PMID- 25621177
TI  - The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs) to Identify
      Osteoclast Defects in Rare Genetic Bone Disorders.
AB  - More than 500 rare genetic bone disorders have been described, but for many of
      them only limited treatment options are available. Challenges for studying these
      bone diseases come from a lack of suitable animal models and unavailability of
      skeletal tissues for studies. Effectors for skeletal abnormalities of bone
      disorders may be abnormal bone formation directed by osteoblasts or anomalous
      bone resorption by osteoclasts, or both. Patient-specific induced pluripotent
      stem cells (iPSCs) can be generated from somatic cells of various tissue sources
      and in theory can be differentiated into any desired cell type. However,
      successful differentiation of hiPSCs into functional bone cells is still a
      challenge. Our group focuses on the use of human iPSCs (hiPSCs) to identify
      osteoclast defects in craniometaphyseal dysplasia. In this review, we describe
      the impact of stem cell technology on research for better treatment of such
      disorders, the generation of hiPSCs from patients with rare genetic bone
      disorders and current protocols for differentiating hiPSCs into osteoclasts. 

PMID- 25621178
TI  - Percutaneous Cryoablation of Metastatic Lesions from Colorectal Cancer: Efficacy
      and Feasibility with Survival and Cost-Effectiveness Observations.
AB  - PURPOSE: To assess feasibility, complications, local tumor recurrences, overall
      survival (OS) and estimates of cost-effectiveness for multi-site cryoablation
      (MCA) of oligo-metastatic colorectal cancer (mCRC) in a prospective study.
      MATERIALS AND METHODS: 111 CT and/or US-guided percutaneous MCA procedures were
      performed on 151 tumors in 59 oligo mCRC patients. Mean patient age was 63 years
      (range 21-92 years), consisting of 29 males and 30 females. Tumor location was
      grouped according to common metastatic sites. Median OS was determined using the
      Kaplan-Meier. Estimates of MCA costs per LYG were compared to historical values
      for systemic therapies. RESULTS: A mean 1.9 MCAs per patient were performed with
      a median clinical follow-up of 12 months. Major complication and local recurrence
      rates were 8% (9/111) and 12% (18/151), respectively. Median overall-survival
      (OS) was 23.6 months with an estimated 3-year survival rate of ~30%. Cryoablation
      remained cost effective with or without the presence of systemic therapies, with
      an adjunctive cost-effectiveness ratio (ACER) of $39,661-$85,580 per LYG.
      CONCLUSIONS: Multi-site cryoablation had very low complication and local
      recurrence rates, and was able to provide local control even for diverse soft
      tissue locations. Even as an adjunct to systemic therapies, MCA appeared cost
      effective, with apparent increased survival.

PMID- 25621179
TI  - Assessing Colorectal Cancer Screening Behaviors and Knowledge among At-Risk
      Hispanics in Southern New Mexico.
AB  - PURPOSE: Colorectal cancer (CRC) mortality rates in New Mexico (NM) continue to
      be higher than national rates. Hispanic CRC mortality rates in NM surpass those
      of overall Hispanics in the US. This study was designed to characterize and
      understand factors contributing to low CRC screening rates in this border region.
      METHODS: A CRC Knowledge Assessment Survey (KAS) was administered in either
      English or Spanish to 247 individuals attending community events throughout
      southern NM. A subset of these individuals completed an online CRC risk
      assessment survey managed by the National Cancer Institute (NCI). Data analysis
      tested for significant differences in knowledge, physician-patient CRC
      interactions, CRC risk level perception, and screening rates across diverse
      ethnic and age groups. RESULTS: Both CRC knowledge and physician-patient CRC
      interactions were positively associated with participant screening history.
      Significant age and ethnic differences for CRC knowledge, physician-patient CRC
      interactions, and screening history in the NM border sample were also seen. Age
      eligible Hispanics (50+) as well as those less than 50 years of age had lower CRC
      knowledge and were less likely to engage in physician-patient CRC interactions
      than non-Hispanic Whites (NHWs). The age-eligible Hispanics also reported lower
      CRC screening rates than their NHW counterparts. CONCLUSIONS: Low CRC knowledge
      and limited physician-patient CRC interactions appear to contribute to low
      screening rates in this NM population. Expanding education and outreach efforts
      for this border population are essential to promote early CRC detection and
      thereby decrease overall CRC mortality rates.

PMID- 25621180
TI  - Toolkit for Community-engaged Wellness Mapping.

PMID- 25621182
TI  - Consensus recommendations on rater training and certification.
AB  - There is currently no accepted standard for the clinical research industry to
      follow when selecting and training raters to administer rating scales in clinical
      neuroscience trials. This article offers guidelines, based on expert
      recommendations of the CNS Summit Rater Training and Certification Committee, for
      selecting, training, and evaluating raters. The article also defines terminology
      and offers recommendations for considering raters with prior training and
      certification. These guidelines are intended for investigators, pharmaceutical
      companies, contract research organizations, and other entities involved in
      clinical neuroscience trials. 

PMID- 25621181
TI  - Differential Effect of Active Smoking on Gene Expression in Male and Female
      Smokers.
AB  - Smoking is the second leading cause of preventable death in the United States.
      Cohort epidemiological studies have demonstrated that women are more vulnerable
      to cigarette-smoking induced diseases than their male counterparts, however, the
      molecular basis of these differences has remained unknown. In this study, we
      explored if there were differences in the gene expression patterns between male
      and female smokers, and how these patterns might reflect different sex-specific
      responses to the stress of smoking. Using whole genome microarray gene expression
      profiling, we found that a substantial number of oxidant related genes were
      expressed in both male and female smokers, however, smoking-responsive genes did
      indeed differ greatly between male and female smokers. Gene set enrichment
      analysis (GSEA) against reference oncogenic signature gene sets identified a
      large number of oncogenic pathway gene-sets that were significantly altered in
      female smokers compared to male smokers. In addition, functional annotation with
      Ingenuity Pathway Analysis (IPA) identified smoking-correlated genes associated
      with biological functions in male and female smokers that are directly relevant
      to well-known smoking related pathologies. However, these relevant biological
      functions were strikingly overrepresented in female smokers compared to male
      smokers. IPA network analysis with the functional categories of immune and
      inflammatory response gene products suggested potential interactions between
      smoking response and female hormones. Our results demonstrate a striking
      dichotomy between male and female gene expression responses to smoking. This is
      the first genome-wide expression study to compare the sex-specific impacts of
      smoking at a molecular level and suggests a novel potential connection between
      sex hormone signaling and smoking-induced diseases in female smokers.

PMID- 25621184
TI  - Toward impacting medical and psychiatric comorbidities in persons with
      intellectual/developmental disabilities: an initial prospective analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of
      psychiatric medical services, counseling, and behavioral treatments for adult
      patients with intellectual disabilities plus behavioral disorders and/or
      emotional distress. METHODS: Behavioral and medical data were collected at six
      and 12 months for a consecutive series of 141 adult patients with mild, moderate,
      or severe/profound intellectual disabilities who had been referred to a dual
      diagnosis mental health clinic, and treatment outcomes were compared. RESULTS:
      Most improvement in behavioral problem severity occurred at six months, then
      plateaued. Treatment improvement for subjects with anxiety disorders was
      statistically significant across all interventions. In this sample, as expected,
      patients with intellectual disability had higher incidences of medical illnesses
      than the general population. CONCLUSIONS: Subjects with more behavioral (overt)
      symptoms tended to receive referrals for behavioral support, and subjects with
      less overt symptoms were referred to counseling. In a follow-up study, similar
      individuals with moderate intellectual disabilities will be seen psychiatrically,
      but then randomly assigned to either supportive counseling or behavior support,
      or both. They will be followed prospectively, to determine the relative benefits
      of supportive psychotherapy, behavior support, or a combination, and for what
      duration of time the treatment should be continued.

PMID- 25621183
TI  - Antidepressant use and body mass index change in overweight adolescents: a
      historical cohort study.
AB  - OBJECTIVE: Given the limited empirical data on antidepressant use and weight
      change in children, we performed a historical cohort study to assess change in
      age- and sex-standardized body mass index associated with antidepressant use
      among overweight adolescents diagnosed with a depressive disorder. METHODS: We
      systematically reviewed electronic medical records from a tertiary academic
      medical center and identified adolescents (age 13-18 years) who were overweight
      (body mass index >85th percentile) and had a depression diagnosis. Patients were
      seen from January 1, 2000, through January 1, 2010. Age- and sex-standardized
      body mass index scores were calculated at initiation of antidepressant medication
      and at the end of treatment. Unmedicated patients had baseline and final age- and
      sex-standardized body mass index calculated using the first and last recorded
      measurements in the study period (maximum time between measures was 5 years).
      RESULTS: In total, 435 patients (301 female) met our inclusion criteria; of
      these, 255 were prescribed an antidepressant (selective serotonin reuptake
      inhibitor, serotonin norepinephrine reuptake inhibitor, tricyclic antidepressant,
      or dopamine-norepinephrine reuptake inhibitor). Age- and sex-standardized body
      mass index significantly increased (F1,193=14.34; P<0.001) only for adolescents
      treated with selective serotonin reuptake inhibitors. For patients receiving
      other medications or no medication, age- and sex-standardized body mass index did
      not change significantly. CONCLUSION: This study provides initial empiric
      evidence for a link between selective serotonin reuptake inhibitor use and weight
      gain in already overweight adolescents. Further study of antidepressant use and
      weight gain in other pediatric populations and in prospective studies is
      warranted.

PMID- 25621185
TI  - ECT-induced Mania.
AB  - Electroconvulsive therapy can induce mania. A recent change in the Diagnostic and
      Statistical Manuel of Mental Disorders, Fifth Edition classifies
      electroconvulsive therapy-induced manic episodes as a bipolar type I diagnosis.
      There are no current established guidelines to treat such condition. The
      following clinical vignette describes a vignette in which a manic episode
      occurred following electroconvulsive therapy treatment. This case report examines
      the potential benefit of prescribing mood stabilizers during the acute episode
      and for maintenance care. 

PMID- 25621187
TI  - Patient aggression: is the clinical practice setting safe?
AB  - Over the past 20 or so years, a number of studies have examined patient
      aggression toward healthcare professionals. While the majority of these studies
      has focused on healthcare professionals in the fields of emergency medicine,
      psychiatry, and primary care, available data extends beyond these three
      specialties. Studies have been done in the United States, other English-speaking
      countries, and elsewhere- all reporting surprisingly high rates of patient
      aggression. Results indicate that patient aggression toward healthcare
      professionals is common and worldwide. In addition, one study examined aggressive
      patient behaviors as reported by the patients themselves, and their self-report
      data reinforce the mainstream data. While these data do not enable us to
      determine if patient aggression is genuinely on the increase, we can safely say
      that these behaviors are rampant. 

PMID- 25621186
TI  - Our current understanding of adult ADHD.

PMID- 25621188
TI  - Requests for disclosure of psychological testing information.

PMID- 25621189
TI  - Proceedings of the third joint symposium on neuroacanthocytosis and
      neurodegeneration with brain iron accumulation: from benchside to bedside.

PMID- 25621190
TI  - HPMA Copolymer CXCR4 Antagonist Conjugates Substantially Inhibited the Migration
      of Prostate Cancer Cells.
AB  - A N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-CXCR4 antagonist (BKT140)
      conjugate (P-BKT140) was developed and its biological activities were tested.
      Both free BKT140 and monomer MA-GGPLGLAG-BKT140 (MA is methacryloyl) were
      prepared by solid phase synthesis. P-BKT140 was prepared by reversible addition
      fragmentation chain transfer (RAFT) copolymerization of monomers HPMA and MA
      GGPLGLAG-BKT140. The in vitro results show that the free BKT140 and P-BKT140 have
      similar cytotoxicity against human prostate carcinoma PC-3 cells, indicating that
      conjugation of BKT140 to HPMA did not significantly impact the cytotoxicity of
      BKT140. Both BKT140 and P-BKT140 inhibited the CXCL12-induced migration of PC-3
      prostate cancer cells, but the P-BKT140 conjugate possessed a substantially
      higher inhibition activity than free BKT140.

PMID- 25621191
TI  - Serial block face-scanning electron microscopy: a method to study retinal
      degenerative phenotypes.
AB  - Retinal degenerative conditions can vary in their clinical features and often
      present with subtle phenotypic features before the onset of clinically overt
      disease. To capture these isolated events that precipitate disease, large
      representative areas of the retina must be imaged at high resolution. Compared to
      light microscopic methods, traditional electron microscopy can provide images at
      sufficient resolution to detect subtle pathologic changes in the retina, but are
      limited to the area being surveyed. The advent of serial block face-scanning
      electron microscopy (SBF-SEM) provides the resolution needed with the
      unprecedented advantage of imaging large volumes of retinal tissue. Furthermore,
      automation of SBF-SEM bypasses errors from manual sectioning and can produce
      reliable serial sections as thin as 25 nanometers. Moreover, the three
      dimensional structures generated can highlight cellular connectivity and
      interactions in the retina and reveal pathological changes. Using SBF-SEM, we
      have identified subtle phenotypic features in mouse models of various human
      retinal dystrophies. This method will allow researchers to identify and monitor
      the time course of these pathologies. This article provides details on SBF-SEM
      methodology and its application to mouse models of retinal degeneration.

PMID- 25621192
TI  - Intravitreal Anti-Vascular Endothelial  Growth Factor in Retinopathy of 
      Prematurity: Several Years On.

PMID- 25621193
TI  - Attitudes toward E-Cigarettes, Reasons for Initiating E-Cigarette Use, and
      Changes in Smoking Behavior after Initiation: A Pilot Longitudinal Study of
      Regular Cigarette Smokers.
AB  - OBJECTIVES: We examined 1) changes in smoking and vaping behavior and associated
      cotinine levels and health status among regular smokers who were first-time e
      cigarette purchasers and 2) attitudes, intentions, and restrictions regarding e
      cigarettes. METHODS: We conducted a pilot longitudinal study with assessments of
      the aforementioned factors and salivary cotinine at weeks 0, 4, and 8.
      Eligibility criteria included being >=18 years old, smoking >=25 of the last 30
      days, smoking >=5 cigarettes per day (cpd), smoking regularly >=1 year, and not
      having started using e-cigarettes. Of 72 individuals screened, 40 consented, 36
      completed the baseline survey, and 83.3% and 72.2% were retained at weeks 4 and
      8, respectively. RESULTS: Participants reduced cigarette consumption from
      baseline to week 4 and 8 (p's < 0.001); 23.1% reported no cigarette use in the
      past month at week 8. There was no significant decrease in cotinine from baseline
      to week 4 or 8 (p's = ns). At week 8, the majority reported improved health
      (65.4%), reduced smoker's cough (57.7%), and improved sense of smell (53.8%) and
      taste (50.0%). The majority believed that e-cigarettes versus regular cigarettes
      have fewer health risks (97.2%) and that e-cigarettes have been shown to help
      smokers quit (80.6%) and reduce cigarette consumption (97.2%). In addition, the
      majority intended to use e-cigarettes as a complete replacement for regular
      cigarettes (69.4%) and reported no restriction on e-cigarette use in the home
      (63.9%) or car (80.6%). CONCLUSIONS: Future research is needed to document the
      long-term impact on smoking behavior and health among cigarette smokers who
      initiate use of e-cigarettes.

PMID- 25621194
TI  - Automated Lung Segmentation and Image Quality Assessment for Clinical 3D/4D
      Computed Tomography.
AB  - Four-dimensional computed tomography (4DCT) provides not only a new dimension of
      patient-specific information for radiation therapy planning and treatment but
      also a challenging scale of data volume to process and analyze. Manual analysis
      using existing 3D tools is unable to keep up with vastly increased 4D data
      volume, automated processing and analysis are thus needed to process 4DCT data
      effectively and efficiently. In this work, we applied ideas and algorithms from
      image/signal processing, computer vision and machine learning to 4DCT lung data
      so that lungs can be reliably segmented in a fully-automated manner, lung
      features can be visualized and measured on-the-fly via user interactions, and
      data quality classifications can be computed in a robust manner. Comparisons of
      our results with an established treatment planning system and calculation by
      experts demonstrated negligible discrepancies (within +/-2%) for volume
      assessment but one to two orders of magnitude performance enhancement. An
      empirical Fourier-analysis-based quality measure delivered performances closely
      emulating human experts. Three machine learners are inspected to justify the
      viability of machine learning techniques used to robustly identify data quality
      of 4DCT images in the scalable manner. The resultant system provides tools that
      speeds up 4D tasks in the clinic and facilitates clinical research to improve
      current clinical practice.

PMID- 25621195
TI  - beta2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator
      function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow
      and oxidative metabolism.
AB  - BACKGROUND: Endothelial dysfunction is associated with vascular risk factors such
      as dyslipidemia, hypertension, and diabetes, leading to coronary atherosclerosis.
      Sympathetic stress using cold-pressor testing (CPT) has been used to measure
      coronary endothelial function in humans with positron emission tomography (PET)
      myocardial blood flow (MBF) imaging, but is not practical in small animal models.
      This study characterized coronary vasomotor function in mice with [(11)C]acetate
      micro-PET measurements of nitric-oxide-mediated endothelial flow reserve (EFRNOM)
      (adrenergic-stress/rest MBF) and myocardial oxygen consumption (MVO2) using
      salbutamol beta2-adrenergic-activation. METHODS: [(11)C]acetate PET MBF was
      performed at rest + salbutamol (SB 0.2, 1.0 MUg/kg/min) and norepinephrine (NE
      3.2 MUg/kg/min) stress to measure an index of MBF response. beta-adrenergic
      specificity of NE was evaluated by pretreatment with alpha-adrenergic-antagonist
      phentolamine (PHE), and beta2-selectivity was assessed using SB. RESULTS:
      Adjusting for changes in heart rate * systolic blood pressure product (RPP), the
      same stress/rest MBF ratio of 1.4 was measured using low-dose SB and NE in normal
      mice (equivalent to human CPT response). The MBF response was correlated with
      changes in MVO2 (p = 0.02). Nitric oxide synthase (NOS)-inhibited mice (N(g)
      nitro-L-arginine methyl ester (L-NAME) pretreatment and endothelial nitric oxide
      synthase (eNOS) knockout) were used to assess the EFRNOM, in which the low-dose
      SB- and NE-stress MBF responses were completely blocked (p = 0.02). With high
      dose SB-stress, the MBF ratio was reduced by 0.4 following NOS inhibition (p =
      0.03). CONCLUSIONS: Low-dose salbutamol beta2-adrenergic-stress [(11)C]acetate
      micro-PET imaging can be used to measure coronary-specific EFRNOM in mice and may
      be suitable for assessment of endothelial dysfunction in small animal models of
      disease and evaluation of new therapies.

PMID- 25621197
TI  - Test-retest variability of adenosine A2A binding in the human brain with (11)C
      TMSX and PET.
AB  - BACKGROUND: The goal of the present study was to evaluate the reproducibility of
      cerebral adenosine A2A receptor (A2AR) quantification using (11)C-TMSX and PET in
      a test-retest study. METHODS: Five healthy volunteers were studied twice. The
      test-retest variability was assessed for distribution volume (V T) and binding
      potential relative to non-displaceable uptake (BPND) based on either metabolite
      corrected arterial blood sampling or a reference region. The cerebral cortex and
      centrum semiovale were used as candidate reference regions. RESULTS: Test-retest
      variability of V T was good in all regions (6% to 13%). In the putamen, BPND
      using the centrum semiovale displayed a lower test-retest variability (3%) than
      that of BPND using the cerebral cortex as a reference region (5%). The
      noninvasive method showed a higher or similar level of test-retest
      reproducibility compared to the invasive method. CONCLUSIONS: Binding
      reproducibility is sufficient to use (11)C-TMSX as a tool to measure the change
      in A2AR in the human brain.

PMID- 25621196
TI  - FBPA PET in boron neutron capture therapy for cancer: prediction of (10)B
      concentration in the tumor and normal tissue in a rat xenograft model.
AB  - BACKGROUND: Boron neutron capture therapy (BNCT) is a molecular radiation
      treatment based on the (10)B (n, alpha) (7)Li nuclear reaction in cancer cells,
      in which delivery of (10)B by 4-borono-phenylalanine conjugated with fructose
      (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2
      (18) F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of
      BPA-fr before BNCT. However, because of the difference in chemical structure
      between BPA-fr and FBPA and the difference in the dose administered between BPA
      fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET
      for BPA-fr accumulation in the tumor and normal tissues is not yet clearly
      proven. We conducted this study to validate FBPA PET as a useful test to predict
      the accumulation of BPA-fr in the tumor and normal tissues before BNCT. METHODS:
      RGC-6 rat glioma cells (1.9 * 10(7)) were implanted subcutaneously in seven male
      F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed
      on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h
      after intravenous injection of the FBPA solution (30.5 +/- 0.7 MBq, 1.69 +/- 1.21
      mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues
      was estimated as a percentage of the injected dose per gram (%ID/g). One hour
      after the PET/CT scan, BPA-fructose (167.32 +/- 18.65 mg/kg) was injected
      intravenously, and the rats were dissected 1 h after the BPA-fr injection. The
      absolute concentration of (10)B in the autopsied tissues and blood was measured
      by inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS:
      The highest absolute concentration of (10)B determined by ICP-OES was found in
      the kidney (4.34 +/- 0.84 %ID/g), followed by the pancreas (2.73 +/- 0.63 %ID/g),
      and the tumor (1.44 +/- 0.44 %ID/g). A significant positive correlation was found
      between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05).
      CONCLUSIONS: FBPA PET can reliably predict accumulation of BPA-fr in the tumor as
      well as normal tissues.

PMID- 25621198
TI  - Sunlight-induced rapid and efficient biogenic synthesis of silver nanoparticles
      using aqueous leaf extract of Ocimum sanctum Linn. with enhanced antibacterial
      activity.
AB  - BACKGROUND: Nanotechnology is now regarded as a distinct field of research in
      modern science and technology with multifaceted areas including biomedical
      applications. Among the various approaches currently available for the generation
      of metallic nanoparticles, biogenic synthesis is of increasing demand for the
      purpose of green nanotechnology. Among various natural sources, plant materials
      are the most readily available template-directing matrix offering cost
      effectiveness, eco-friendliness, and easy handling. Moreover, the inherent
      pharmacological potentials of these medicinal plant extracts offer added
      biomedical implementations of the synthesized metal nanoparticles. RESULTS: A
      robust practical method for eco-friendly synthesis of silver nanoparticles using
      aqueous leaf extract of Ocimum sanctum (Tulsi) as both reducing and capping
      agent, under the influence of direct sunlight has been developed without applying
      any other chemical additives. The nanoparticles were characterized with the help
      of UV-visible spectrophotometer and transmission electron microscopy (TEM). The
      prepared silver nanoparticles exhibited considerable antibacterial activity. The
      effects were more pronounced on non-endospore-forming Gram-positive bacteria
      viz., Staphylococcus aureus, Staphylococcus epidermidis, and Listeria
      monocytogenes than endospore-forming species Bacillus subtilis. The nanoparticles
      also showed prominent activity on Gram-negative human pathogenic Salmonella
      typhimurium, Escherichia coli, Pseudomonas aeruginosa, and plant pathogenic
      Pantoea ananatis. A bactericidal mode of action was observed for both Gram
      positive and Gram-negative bacteria by the nanoparticles. CONCLUSIONS: We have
      developed a very simple, efficient, and practical method for the synthesis of
      silver nanoparticles using aqueous leaf extract of O. sanctum under the influence
      of direct sunlight. The biosynthesis of silver nanoparticles making use of such a
      traditionally important medicinal plant without applying any other chemical
      additives, thus offers a cost-effective and environmentally benign route for
      their large-scale commercial production. The nanoparticles dispersed in the
      mother solution showed promising antibacterial efficacy. Graphical
      AbstractSunlight-induced rapid and efficient biogenic synthesis of silver
      nanoparticles using aqueous leaf extract of Ocimum sanctum Linn. with enhanced
      antibacterial activity.

PMID- 25621199
TI  - Prevalence and Correlates of Indoor Tanning and Sunless Tanning Product Use among
      Female Teens in the United States.
AB  - BACKGROUND: Indoor tanning (IT) before the age of 35 increases melanoma risk by
      75%. Nevertheless, IT and sunless tanning product (STP) use have gained
      popularity among youth. However, there are limited data on the prevalence and
      sociodemographic correlates of both IT and STP use in a representative sample of
      American teens. METHODS: Teenage females (N=778) aged 12-18 years were recruited
      as part of an on-going longitudinal study conducted between May 2011 and May
      2013. Descriptive statistics explored IT and STP usage in teen females at
      baseline. Logistic regression was used to determine sociodemographic correlates
      of IT and STP use. RESULTS: Approximately 16% of female teens engaged in IT
      behavior and 25% engaged in using STPs. Female teens living in non-metropolitan
      areas were 82% more likely to indoor tan compared to those in metropolitan areas
      (OR=1.82, 95% CI:1.07-3.10). Age, geographic regions, and race increased the
      likelihood of IT and STP use. CONCLUSIONS: Results indicate a significant
      proportion of teen females engage in IT and STP use. There was evidence that in
      teens that have never used IT before, STP use precedes IT initiation. Given the
      evidence for increased IT in rural populations, research focused on rural tanning
      bed use is needed.

PMID- 25621200
TI  - Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment.
AB  - Treatment of cancer using nanoparticle-based approaches relies on the rational
      design of carriers with respect to size, charge, and surface properties. Polymer
      based nanomaterials, inorganic materials such as gold, iron oxide, and silica as
      well as carbon based materials such as carbon nanotubes and graphene are being
      explored extensively for cancer therapy. The challenges associated with the
      delivery of these nanoparticles depend greatly on the type of cancer and stage of
      development. This review highlights design considerations to develop nanoparticle
      based approaches for overcoming physiological hurdles in cancer treatment, as
      well as emerging research in engineering advanced delivery systems for the
      treatment of primary, metastatic, and multidrug resistant cancers. A growing
      understanding of cancer biology will continue to foster development of
      intelligent nanoparticle-based therapeutics that take into account diverse
      physiological contexts of changing disease states to improve treatment outcomes.

PMID- 25621201
TI  - The audacity of interpretation: Protecting patients or piling on?

PMID- 25621202
TI  - Healthy Aging in China.
AB  - China has aged rapidly and the rate is accelerating in decades to come. We review
      positive and negative forces for healthy aging in China now and in the future.
      The most positive force is the spectacular growth in education over time
      especially for Chinese women, which should improve all dimensions of cognitive
      and physical health and eliminate vast gender disparities in healthy aging that
      currently exist. Other positive forces include increasing detection and treatment
      of disease and the availability of health insurance and health services so that
      diseases like hypertension and diabetes do not remain silent killers in China.
      Transparency is eased on the research level by publicly available data such as
      CHARLS, a sharp departure from prior scientific norm in China. Negative forces
      center on disturbing trends in personal health behaviors such as growing rates of
      smoking (among men) and obesity (for both genders), and pollution-,especially in
      urban centers. Public health campaigns and incentives are needed on all these
      fronts so that predictable long-term consequences of these behaviors on older age
      disease are not realized. There will not be a simple demographic fix to healthy
      aging in China as fertility rates are unlikely to rise much, while migration will
      likely continue to rise leaving growing numbers of elderly parents geographically
      separated from their adult children. Government policy will have to allow
      migration of elderly parents to live with their adult children while reducing the
      rigid connection of policy (health insurance and health services) with place of
      residence.

PMID- 25621203
TI  - Central processing in the mushroom bodies.
AB  - The mushroom bodies in the insect brain serve as a central information processing
      area. Here, focusing mainly on olfaction, we discuss functionally related roles
      the mushroom bodies play in signal gain control, response sparsening, the
      separation of similar signals (decorrelation), and learning and memory. In sum,
      the mushroom bodies assemble and format a context-appropriate representation of
      the insect's world.

PMID- 25621204
TI  - Custom Mentholation of Commercial Cigarettes for Research Purposes.
AB  - In the U.S. menthol remains the sole permitted characterizing cigarette flavor
      additive in part because efforts to link menthol cigarette use to increased
      tobacco-related disease risk have been inconclusive. To perform definitive
      studies, cigarettes that differ only in menthol content are required, yet these
      are not commercially available. We prepared research cigarettes differing only in
      menthol content by deposition of L-menthol vapor directly onto commercial
      nonmenthol cigarettes, and developed a method to measure a cigarette's menthol
      and nicotine content. With our custom-mentholation technique we achieved the
      desired moderately high menthol content (as compared to commercial brands) of 6.7
      +/- 1.0 mg/g (n = 25) without perturbing the cigarettes' nicotine content (17.7
      +/- 0.7 mg/g [n = 25]). We also characterized other pertinent attributes of our
      custom-mentholated cigarettes, including percent transmission of menthol and
      nicotine to mainstream smoke and the rate of loss of menthol over time during
      storage at room temperature. We are currently using this simple mentholation
      technique to investigate the differences in human exposure to selected chemicals
      in cigarette smoke due only to the presence of the added menthol. Our cigarettes
      will also aid in the elucidation of the effects of menthol on the toxicity of
      tobacco smoke.

PMID- 25621205
TI  - Rehabilitation in spinal infection diseases.
AB  - Spinal cord infections were the diseases defined by Hypocrite yet the absence of
      modern medicine and there was not a real protocol in rehabilitation although
      there were many aspects in surgical treatment options. The patients whether
      surgically or conservatively treated had a lot of neurological, motor, and
      sensory disturbances. Our clinic has quite experience from our previous
      researchs. Unfortunately, serious spinal cord infections are still present in our
      region. In these patients the basic rehabilitation approaches during early, pre
      operation, post-operation period and in the home environment will provide
      significant contributions to improve the patients' sensory and motor skills,
      develop the balance and proriocaption, increase the independence of patients in
      daily living activities and minimize the assistance of other people. There is
      limited information in the literature related with the nature of the
      rehabilitation programmes to be applied for patients with spinal infections. The
      aim of this review is to share our clinic experience and summarise the
      publications about spinal infection rehabilitation. There are very few studies
      about the rehabilitation of spinal infections. There are still not enough studies
      about planning and performing rehabilitation programs in these patients.
      Therefore, a comprehensive rehabilitation programme during the hospitalisation
      and home periods is emphasised in order to provide optimal management and prevent
      further disability. 

PMID- 25621206
TI  - Rehabilitation of spinal cord injuries.
AB  - Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum
      to the cauda equina which occurs as a result of compulsion, incision or
      contusion. The most common causes of SCI in the world are traffic accidents,
      gunshot injuries, knife injuries, falls and sports injuries. There is a strong
      relationship between functional status and whether the injury is complete or not
      complete, as well as the level of the injury. The results of SCI bring not only
      damage to independence and physical function, but also include many complications
      from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure
      ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity,
      autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive
      disorders are frequent complications after SCI. SCI leads to serious disability
      in the patient resulting in the loss of work, which brings psychosocial and
      economic problems. The treatment and rehabilitation period is long, expensive and
      exhausting in SCI. Whether complete or incomplete, SCI rehabilitation is a long
      process that requires patience and motivation of the patient and relatives. Early
      rehabilitation is important to prevent joint contractures and the loss of muscle
      strength, conservation of bone density, and to ensure normal functioning of the
      respiratory and digestive system. An interdisciplinary approach is essential in
      rehabilitation in SCI, as in the other types of rehabilitation. The team is led
      by a physiatrist and consists of the patients' family, physiotherapist,
      occupational therapist, dietician, psychologist, speech therapist, social worker
      and other consultant specialists as necessary. 

PMID- 25621207
TI  - Acute complications of spinal cord injuries.
AB  - The aim of this paper is to give an overview of acute complications of spinal
      cord injury (SCI). Along with motor and sensory deficits, instabilities of the
      cardiovascular, thermoregulatory and broncho-pulmonary system are common after a
      SCI. Disturbances of the urinary and gastrointestinal systems are typical as well
      as sexual dysfunction. Frequent complications of cervical and high thoracic SCI
      are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal
      temperature control and disturbance of sweating, vasodilatation and autonomic
      dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic
      response, elicited by stimuli below the level of injury. The symptoms may be mild
      like skin rash or slight headache, but can cause severe hypertension, cerebral
      haemorrhage and death. All personnel caring for the patient should be able to
      recognize the symptoms and be able to intervene promptly. Disturbance of
      respiratory function are frequent in tetraplegia and a primary cause of both
      short and long-term morbidity and mortality is pulmonary complications. Due to
      physical inactivity and altered haemostasis, patients with SCI have a higher risk
      of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent
      complications which need to be addressed. The psychological stress associated
      with SCI may lead to anxiety and depression. Knowledge of possible complications
      during the acute phase is important because they may be life threatening and/ or
      may lead to prolonged rehabilitation. 

PMID- 25621208
TI  - Chronic complications of spinal cord injury.
AB  - Spinal cord injury (SCI) is a serious medical condition that causes functional,
      psychological and socioeconomic disorder. Therefore, patients with SCI experience
      significant impairments in various aspects of their life. The goals of
      rehabilitation and other treatment approaches in SCI are to improve functional
      level, decrease secondary morbidity and enhance health-related quality of life.
      Acute and long-term secondary medical complications are common in patients with
      SCI. However, chronic complications especially further negatively impact on
      patients' functional independence and quality of life. Therefore, prevention,
      early diagnosis and treatment of chronic secondary complications in patients with
      SCI is critical for limiting these complications, improving survival, community
      participation and health-related quality of life. The management of secondary
      chronic complications of SCI is also important for SCI specialists, families and
      caregivers as well as patients. In this paper, we review data about common
      secondary long-term complications after SCI, including respiratory complications,
      cardiovascular complications, urinary and bowel complications, spasticity, pain
      syndromes, pressure ulcers, osteoporosis and bone fractures. The purpose of this
      review is to provide an overview of risk factors, signs, symptoms, prevention and
      treatment approaches for secondary long-term complications in patients with SCI. 

PMID- 25621209
TI  - Current and future surgery strategies for spinal cord injuries.
AB  - Spinal cord trauma is a prominent cause of mortality and morbidity. In developed
      countries a spinal cord injury (SCI) occurs every 16 min. SCI occurs due to
      tissue destruction, primarily by mechanical and secondarily ischemic. Primary
      damage occurs at the time of the injury. It cannot be improved. Following the
      primary injury, secondary harm mechanisms gradually result in neuronal death. One
      of the prominent causes of secondary harm is energy deficit, emerging from
      ischemia, whose main cause in the early stage, is impaired perfusion. Due to the
      advanced techniques in spinal surgery, SCI is still challenging for surgeons.
      Spinal cord doesn't have a self-repair property. The main damage occurs at the
      time of the injury primarily by mechanical factors that cannot be improved.
      Secondarily mechanisms take part in the following sections. Spinal compression
      and neurological deficit are two major factors used to decide on surgery.
      According to advanced imaging techniques the classifications systems for spinal
      injury has been changed in time. Aim of the surgery is to decompress the spinal
      channel and to restore the spinal alinement and mobilize the patient as soon as
      possible. Use of neuroprotective agents as well as methods to achieve cell
      regeneration in addition to surgery would contribute to the solution. 

PMID- 25621210
TI  - Current and future medical therapeutic strategies for the functional repair of
      spinal cord injury.
AB  - Spinal cord injury (SCI) leads to social and psychological problems in patients
      and requires costly treatment and care. In recent years, various pharmacological
      agents have been tested for acute SCI. Large scale, prospective, randomized,
      controlled clinical trials have failed to demonstrate marked neurological benefit
      in contrast to their success in the laboratory. Today, the most important problem
      is ineffectiveness of nonsurgical treatment choices in human SCI that showed
      neuroprotective effects in animal studies. Recently, attempted cellular therapy
      and transplantations are promising. A better understanding of the pathophysiology
      of SCI started in the early 1980s. Research had been looking at neuroprotection
      in the 1980s and the first half of 1990s and regeneration studies started in the
      second half of the 1990s. A number of studies on surgical timing suggest that
      early surgical intervention is safe and feasible, can improve clinical and
      neurological outcomes and reduce health care costs, and minimize the secondary
      damage caused by compression of the spinal cord after trauma. This article
      reviews current evidence for early surgical decompression and nonsurgical
      treatment options, including pharmacological and cellular therapy, as the
      treatment choices for SCI. 

PMID- 25621211
TI  - Subtalar arthroscopy: When, why and how.
AB  - Technique of subtalar arthroscopy is rapidly evolving. Increasing number of
      traditional open procedures for the subtalar joint can now be done
      arthroscopically. It is hoped that less wound complications, faster
      rehabilitation and better cosmetic outcomes can be achieved with this minimally
      invasive technique. 

PMID- 25621212
TI  - Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular
      markers in diabetes.
AB  - Diabetic foot ulcerations have been extensively reported as vascular
      complications of diabetes mellitus associated with a high degree of morbidity and
      mortality. Diabetic foot syndrome (DFS), as defined by the World Health
      Organization, is an "ulceration of the foot (distally from the ankle and
      including the ankle) associated with neuropathy and different grades of ischemia
      and infection". Pathogenic events able to cause diabetic foot ulcers are
      multifactorial. Among the commonest causes of this pathogenic pathway it's
      possible to consider peripheral neuropathy, foot deformity, abnormal foot
      pressures, abnormal joint mobility, trauma, peripheral artery disease. Several
      studies reported how diabetic patients show a higher mortality rate compared to
      patients without diabetes and in particular these studies under filled how
      cardiovascular mortality and morbidity is 2-4 times higher among patients
      affected by type 2 diabetes mellitus. This higher degree of cardiovascular
      morbidity has been explained as due to the observed higher prevalence of major
      cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases,
      and of prevalence and incidence of cardiovascular and cerebrovascular events in
      diabetic patients with foot complications. In diabetes a fundamental pathogenic
      pathway of most of vascular complications has been reported as linked to a
      complex interplay of inflammatory, metabolic and procoagulant variables. These
      pathogenetic aspects have a direct interplay with an insulin resistance,
      subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid
      disorder. Involvement of inflammatory markers such as IL-6 plasma levels and
      resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the
      pathogenetic issue of the a "adipo-vascular" axis that may contribute to
      cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis"
      in patients with type 2 diabetes has been reported as characterized by lower
      plasma levels of adiponectin and higher plasma levels of interleukin-6 thus
      linking foot ulcers pathogenesis to microvascular and inflammatory events. The
      purpose of this review is to highlight the immune inflammatory features of DFS
      and its possible role as a marker of cardiovascular risk in diabetes patients and
      to focus the management of major complications related to diabetes such as
      infections and peripheral arteriopathy. 

PMID- 25621213
TI  - Biotribology of artificial hip joints.
AB  - Hip arthroplasty can be considered one of the major successes of orthopedic
      surgery, with more than 350000 replacements performed every year in the United
      States with a constantly increasing rate. The main limitations to the lifespan of
      these devices are due to tribological aspects, in particular the wear of mating
      surfaces, which implies a loss of matter and modification of surface geometry.
      However, wear is a complex phenomenon, also involving lubrication and friction.
      The present paper deals with the tribological performance of hip implants and is
      organized in to three main sections. Firstly, the basic elements of tribology are
      presented, from contact mechanics of ball-in-socket joints to ultra high
      molecular weight polyethylene wear laws. Some fundamental equations are also
      reported, with the aim of providing the reader with some simple tools for
      tribological investigations. In the second section, the focus moves to artificial
      hip joints, defining materials and geometrical properties and discussing their
      friction, lubrication and wear characteristics. In particular, the features of
      different couplings, from metal-on-plastic to metal-on-metal and ceramic-on
      ceramic, are discussed as well as the role of the head radius and clearance. How
      friction, lubrication and wear are interconnected and most of all how they are
      specific for each loading and kinematic condition is highlighted. Thus, the
      significant differences in patients and their lifestyles account for the high
      dispersion of clinical data. Furthermore, such consideration has raised a new
      discussion on the most suitable in vitro tests for hip implants as simplified
      gait cycles can be too far from effective implant working conditions. In the
      third section, the trends of hip implants in the years from 2003 to 2012 provided
      by the National Joint Registry of England, Wales and Northern Ireland are
      summarized and commented on in a discussion. 

PMID- 25621215
TI  - Hand bone mass in rheumatoid arthritis: A review of the literature.
AB  - Rheumatoid arthritis (RA) is a common chronic inflammatory disease and
      periarticular osteoporosis or osteopenia of the inflamed hand joints is an early
      feature of RA. Quantitative measurement of hand bone loss may be an outcome
      measure for the detection of joint destruction and disease progression in early
      RA. This systematic review examines the published literature reporting hand bone
      mass in patients with RA, particularly those using the dual X-ray absorptiometry
      (DXA) methods. The majority of the studies reported that hand bone loss is
      associated with disease activity, functional status and radiological progression
      in early RA. Quantitative measurement of hand bone mineral density by DXA may be
      a useful and practical outcome measure in RA and may be predictive for
      radiographic progression or functional status in patients with early RA. 

PMID- 25621214
TI  - Cytokines as biochemical markers for knee osteoarthritis.
AB  - Osteoarthritis (OA) is a debilitating degenerative joint disease particularly
      affecting weightbearing joints within the body, principally the hips and knees.
      Current radiographic techniques are insufficient to show biochemical changes
      within joint tissue which can occur many years before symptoms become apparent.
      The need for better diagnostic and prognostic tools is heightened with the
      prevalence of OA set to increase in aging and obese populations. As inflammation
      is increasingly being considered an important part of OAs pathophysiology,
      cytokines are being assessed as possible candidates for biochemical markers.
      Cytokines, both pro- and anti-inflammatory, as well as angiogenic and
      chemotactic, have in recent years been studied for relevant characteristics.
      Biochemical markers show promise in determination of the severity of disease in
      addition to monitoring of the efficacy and safety of disease-modifying OA drugs,
      with the potential to act as diagnostic and prognostic tools. Currently, the
      diagnostic power of interleukin (IL)-6 and the relationship to disease burden of
      IL-1beta, IL-15, tumor necrosis factor-alpha, and vascular endothelial growth
      factor make these the best candidates for assessment. Grouping appropriate
      cytokine markers together and assessing them collectively alongside other bone
      and cartilage degradation products will yield a more statistically powerful tool
      in research and clinical applications, and additionally aid in distinguishing
      between OA and a number of other diseases in which cytokines are known to have an
      involvement. Further large scale studies are needed to assess the validity and
      efficacy of current biomarkers, and to discover other potential biomarker
      candidates. 

PMID- 25621216
TI  - Current strategies for the restoration of adequate lordosis during lumbar fusion.
AB  - Not restoring the adequate lumbar lordosis during lumbar fusion surgery may
      result in mechanical low back pain, sagittal unbalance and adjacent segment
      degeneration. The objective of this work is to describe the current strategies
      and concepts for restoration of adequate lordosis during fusion surgery.
      Theoretical lordosis can be evaluated from the measurement of the pelvic
      incidence and from the analysis of spatial organization of the lumbar spine with
      2/3 of the lordosis given by the L4-S1 segment and 85% by the L3-S1 segment.
      Technical aspects involve patient positioning on the operating table, release
      maneuvers, type of instrumentation used (rod, screw-rod connection, interbody
      cages), surgical sequence and the overall surgical strategy. Spinal osteotomies
      may be required in case of fixed kyphotic spine. AP combined surgery is
      particularly efficient in restoring lordosis at L5-S1 level and should be
      recommended. Finally, not one but several strategies may be used to achieve the
      need for restoration of adequate lordosis during fusion surgery. 

PMID- 25621218
TI  - Overweight and obesity in hip and knee arthroplasty: Evaluation of 6078 cases.
AB  - AIM: To evaluate a possible association between the various levels of obesity and
      peri-operative charac-teristics of the procedure in patients who underwent
      endoprosthetic joint replacement in hip and knee joints. METHODS: We hypothesized
      that obese patients were treated for later stage of osteoarthritis, that more
      conservative implants were used, and the intra-and perioperative complications
      increased for such patients. We evaluated all patients with body mass index (BMI)
      >= 25 who were treated in our institution from January 2011 to September 2013 for
      a primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients
      were split up by the levels of obesity according to the classification of the
      World Health Organization. Average age at the time of primary arthroplasty,
      preoperative Harris Hip Score (HHS), Hospital for Special Surgery score (HSS),
      gender, type of implanted prosthesis, and intra-and postoperative complications
      were evaluated. RESULTS: Six thousand and seventy-eight patients with a BMI >= 25
      were treated with a primary THA or TKA. Age decreased significantly (P < 0.001)
      by increasing obesity in both the THA and TKA. HHS and HSS were at significantly
      lower levels at the time of treatment in the super-obese population (P < 0.001).
      Distribution patterns of the type of endoprostheses used changed with an
      increasing BMI. Peri- and postoperative complications were similar in form and
      quantity to those of the normal population. CONCLUSION: Higher BMI leads to
      endoprosthetic treat-ment in younger age, which is carried out at significantly
      lower levels of preoperative joint function.

PMID- 25621217
TI  - Regeneration of the anterior cruciate ligament: Current strategies in tissue
      engineering.
AB  - Recent advancements in the field of musculoskeletal tissue engineering have
      raised an increasing interest in the regeneration of the anterior cruciate
      ligament (ACL). It is the aim of this article to review the current research
      efforts and highlight promising tissue engineering strategies. The four main
      components of tissue engineering also apply in several ACL regeneration research
      efforts. Scaffolds from biological materials, biodegradable polymers and
      composite materials are used. The main cell sources are mesenchymal stem cells
      and ACL fibroblasts. In addition, growth factors and mechanical stimuli are
      applied. So far, the regenerated ACL constructs have been tested in a few animal
      studies and the results are encouraging. The different strategies, from in vitro
      ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration,
      are under constant development. We expect considerable progress in the near
      future that will result in a realistic option for ACL surgery soon. 

PMID- 25621219
TI  - Cost of external fixation vs external fixation then nailing in bone infection.
AB  - AIM: To study the cost benefit of external fixation vs external fixation then
      nailing in treatment of bone infection by segment transfer. METHODS: Out of 71
      patients with infected nonunion tibia treated between 2003 and 2006, 50 patients
      fitted the inclusion criteria (26 patients were treated by external fixation
      only, and 24 patients were treated by external fixation early removal after
      segment transfer and replacement by internal fixation). Cost of inpatient
      treatment, total cost of inpatient and outpatient treatment till full healing,
      and the weeks of absence from school or work were calculated and compared between
      both groups. RESULTS: The cost of hospital stay and surgery in the group of
      external fixation only was 22.6 +/- 3.3 while the cost of hospital stay and
      surgery in the group of early external fixation removal and replacement by
      intramedullary nail was 26.0 +/- 3.2. The difference was statistically
      significant regarding the cost of hospital stay and surgery in favor of the group
      of external fixation only. The total cost of medical care (surgery, hospital
      stay, treatment outside the hospital including medications, dressing, physical
      therapy, outpatient laboratory work, etc.) in group of external fixation only was
      63.3 +/- 15.1, and total absence from work was 38.6 +/- 6.6 wk. While the group
      of early removal of external fixation and replacement by IM nail, total cost of
      medical care was 38.3 +/- 6.4 and total absence from work or school was 22.7 +/-
      4.1. The difference was statistically significant regarding the total cost and
      absence from work in favor of the group of early removal and replacement by IM
      nail. CONCLUSION: Early removal of external fixation and replacement by
      intramedullary nail in treatment of infected nonunion showed more cost
      effectiveness. Orthopaedic society needs to show the cost effectiveness of
      different procedures to the community, insurance, and health authorities.

PMID- 25621220
TI  - How are those "lost to follow-up" patients really doing? A compliance comparison
      in arthroplasty patients.
AB  - AIM: To determine whether there is a functional difference between patients who
      actively follow-up in the office (OFU) and those who are non-compliant with
      office follow-up visits (NFU). METHODS: We reviewed a consecutive group of 588
      patients, who had undergone total joint arthroplasty (TJA), for compliance and
      functional outcomes at one to two years post-operatively. All patients were given
      verbal instructions by the primary surgeon to return at one year for routine
      follow-up visits. Patients that were compliant with the instructions at one year
      were placed in the OFU cohort, while those who were non-compliant were placed in
      the NFU cohort. Survey mailings and telephone interviews were utilized to obtain
      complete follow-up for the cohort. A chi(2) test and an unpaired t test were used
      for comparison of baseline characteristics. Analysis of covariance was used to
      compare the mean clinical outcomes after controlling for confounding variables.
      RESULTS: Complete follow-up data was collected on 554 of the 588 total patients
      (93%), with 75.5% of patients assigned to the OFU cohort and 24.5% assigned to
      the NFU cohort. We found significant differences between the cohorts with the OFU
      group having a higher mean age (P = 0.026) and a greater proportion of females (P
      = 0.041). No significant differences were found in either the SF12 or WOMAC
      scores at baseline or at 12 mo postoperative. CONCLUSION: Patients who are
      compliant to routine follow-up visits at one to two years post-operation do not
      experience better patient reported outcomes than those that are non-compliant.
      Additionally, after TJA, older women are more likely to be compliant in following
      surgeon instructions with regard to follow-up office care.

PMID- 25621221
TI  - Triangle tilt and humeral surgery: Meta-analysis of efficacy and functional
      outcome.
AB  - AIM: To systematically review and analyze the overall impact and effectiveness of
      bony surgical procedures, the triangle tilt and humeral surgery in a comparative
      manner in permanent obstetric brachial plexus injury (OBPI) patients. METHODS: We
      conducted a literature search and identified original full research articles of
      OBPI patients treated with a secondary bony surgery, particularly addressing the
      limitation of shoulder abduction and functions. Further, we analyzed and compared
      the efficacy and the surgical outcomes of 9 humeral surgery papers with 179
      patients, and 4 of our secondary bony procedure, the triangle tilt surgical
      papers with 86 patients. RESULTS: Seven hundred and thirty-one articles were
      identified, using the search term "brachial plexus" and obstetric or pediatric
      (246 articles) or neonatal (219 articles) or congenital (188 articles) or "birth
      palsy" (121 articles). Further, only a few articles were identified using the
      bony surgery search, osteotomy "brachial plexus" obstetric (35), "humeral
      osteotomy" and "brachial plexus" (17), and triangle tilt "brachial plexus" (14).
      Of all, 12 studies reporting pre- and post- operative or improvement in total
      Mallet functional score were included in this study. Among these, 9 studies
      reported the humeral surgery and 4 were triangle tilt surgery. We used modified
      total Mallet functional score in this analysis. Various studies with humeral
      surgery showed improvement of 1.4, 2.3, 5.0 and 5.6 total Mallet score, whereas
      the triangle tilt surgery showed improvement of 5.0, 5.5, 6.0 and 6.2.
      CONCLUSION: The triangle tilt surgery improves on what was achieved by humeral
      osteotomy in the management of shoulder function in OBPI patients.

PMID- 25621222
TI  - Role of myeloid-derived suppressor cells in autoimmune disease.
AB  - Myeloid-derived suppressor cells (MDSCs) represent an important class of
      immunoregulatory cells that can be activated to suppress T cell functions. These
      MDSCs can inhibit T cell functions through cell surface interactions and the
      release of soluble mediators. MDSCs accumulate in the inflamed tissues and
      lymphoid organs of patients with autoimmune diseases. Much of our knowledge of
      MDSC function has come from studies involving cancer models, however many recent
      studies have helped to characterize MDSC involvement in autoimmune diseases.
      MDSCs are a heterogeneous group of immature myeloid cells with a number of
      different functions for the suppression of T cell responses. However, we have yet
      to fully understand their contributions to the development and regulation of
      autoimmune diseases. A number of studies have described beneficial functions of
      MDSCs during autoimmune diseases, and thus there appears to be a potential role
      for MDSCs in the treatment of these diseases. Nevertheless, many questions remain
      as to the activation, differentiation, and inhibitory functions of MDSCs. This
      review aims to summarize our current knowledge of MDSC subsets and suppressive
      functions in tissue-specific autoimmune disorders. We also describe the potential
      of MDSC-based cell therapy for the treatment of autoimmune diseases and note some
      of hurdles facing the implementation of this therapy.

PMID- 25621223
TI  - Clinical characteristics of biofilms in patients with chronic rhinosinusitis: a
      prospective case-control study.
AB  - Recent studies have indicated that biofilms are involved in the pathogenesis of
      recurrent and recalcitrant chronic rhinosinusitis (CRS). The present study was
      performed to evaluate the presence of biofilms and to evaluate the relationships
      between the presence of biofilms and clinical features of CRS. A total of 33
      patients were included in this study. Maxillary sinus mucosa from 26 CRS patients
      and the ethmoid mucosa from 7 patients undergoing septoplasty were collected.
      Biofilms were evaluated by scanning electron microscopy. Preoperative symptom
      scores, preoperative and intraoperative nasoendoscopic findings, and
      postoperative healing period were compared between the groups. Biofilms were
      detected in 14 (42.4 %) of the 33 patients. Biofilms were present in 13 (50 %) of
      the 26 patients in the CRS group, but in only one (14.3 %) of the seven patients
      in the control group. There were no significant differences in preoperative
      symptom scores or preoperative nasal Lund-Kennedy endoscopic scores between the
      groups. However, the average Lund-Mackay and intraoperative sinus Lund-Kennedy
      endoscopic scores were significantly higher in biofilm-positive than biofilm
      negative patients (P < 0.05). In the follow-up period, the healing time was
      significantly longer in biofilm-positive than biofilm-negative patients (P <
      0.05). This study suggested that the presence of bacterial biofilms may
      contribute to the pathogenesis of CRS and the clinical characteristics of CRS
      patients after endoscopic sinus surgery. 

PMID- 25621224
TI  - A Study on Olfactory Dysfunction in Turkish Population with using Survey Method
      and Validated Olfactory Testing.
AB  - The aim of this study was to evaluate the effect of olfactory dysfunction on
      quality of life (QOL), and to investigate olfactory dysfunction related self
      reported clinical features in Turkish population. The participants were
      questioned about the presence of any olfactory dysfunction. Participants with a
      complaint of olfactory dysfunction were asked to fill out a survey and then a
      validated olfactory test was performed. We asked 2,824 volunteers whether they
      had olfactory dysfunctions or not. A total of 199 (6.7 %) people mentioned that
      they had, and filled out the questions in our survey. The mean age of the
      surveyed population was 44 +/- 15 years. The current investigation produced four
      major findings (1) the feeling of inadequacy due to olfactory dysfunction was
      more common among females than males (2) there was a significant correlation
      between subjective olfactory complaints and objective olfactory testing (3)
      problems in QOL issues are typically reported primarily in the areas of safety
      and nutrition (4) the possible reasons for the olfactory dysfunction according to
      the volunteers were upper respiratory infections including rhinosinusitis (46 %),
      allergic rhinitis (27 %), severe face and head trauma (6.5 %). The effect of
      subjective olfactory dysfunctions on QOL among the Turkish population was
      investigated for the first time. Problems in daily life issues are typically
      reported primarily in the areas of safety and nutrition. 

PMID- 25621225
TI  - Jugular phlebectasia: clinical scenario in India.
AB  - Jugular phlebectasia is fusiform dilatation of internal jugular vein seen in
      childrens. It usually occurs in children but can occur at any age. It usually
      presents as unilateral swelling in the neck found during coughing and shouting.
      It is usually asymptomatic, so it is often ignored or misdiagnosed. Differential
      diagnosis include laryngocele, cavernous hemangioma, cystic hygroma, branchial
      cyst. Treatment is usually conservative as complications like thrombosis and
      horners syndrome are very rare. Non invasive investigations like Doppler sonogram
      and are usually done to diagnose this condition. We report two cases of jugular
      phlebectasia, who presented to our out patient department with history of
      swelling in the right side of neck which increases on crying and shouting.
      Doppler sonogram and ultrasound was done to diagnose the condition. There seems
      be lack of knowledge among medical fraternity in various specialities. So a
      questionnaire was prepared to assess the knowledge among resident doctors,
      general practitioners, Otorhinolaryngologists, paediatricians. Questionnaire was
      posted in social networking sites and the feedback was obtained. Out of the 150
      interns in our hospital, only one (0.66 %) was able to explain about the
      condition. In general practitioners group containing 369 respondents, only 4
      (1.08 %) knew the condition and have seen patients. A pediatricians group
      containing 312 respondents only 23 (7.37 %) pediatricians knew the condition, 289
      (92.62 %) persons had no idea about the treatment. Otorhinolaryngologists group
      containing 328 respondents. 21 (6.40 %) knew the condition, 293 (89.3 %) have no
      idea. The Chi square test shows that the specialty of the respondent like
      pediatrician and ENT practitioner have more knowledge than the other for jugular
      phlebectasia at p < 0.0001. 

PMID- 25621226
TI  - Study of Anatomical Variations on CT in Chronic Sinusitis.
AB  - This is a prospective cross sectional study comprising of 85 patients who were
      having symptoms of sinusitis for more than 12 weeks which were evaluated with the
      help of nasal endoscopy and computed tomography scan to screen the patients of
      chronic-rhinosinusitis for various anatomical variants and to find their
      percentage. The most common variant found to be deviated nasal septum being 88.2
      % followed by concha bullosa being 76.4 %, paradoxical middle turbinate 9 %,
      agger nasi in 7 %. 

PMID- 25621227
TI  - Role of magnetic resonance imaging in evaluation of cerebellopontine angle
      schwannomas.
AB  - The aim of the present study was to evaluate the role of Magnetic Resonance
      Imaging (MRI) to localize and characterize the MR imaging features of
      cerebellopontine angle schwannomas and to compare with surgical/histopathological
      findings. It was a prospective study which included 19 patients, who presented
      with signs and symptoms s/o any lesion in the CP angle and were referred to the
      radiology department for MRI. All patients included in the study were subjected
      to detailed clinical history and physical examination following which MRI was
      carried out on Philips Gyroscan Achieva 1.5 Tesla unit and the standard protocol
      consisted of T1WI, T2WI, DWI and FLAIR images in axial, sagittal and coronal
      planes. Hearing abnormality was the most common presenting complaint in patients
      with CP angle schwannoma's followed by headache and tinnitus. Vestibulocochlear
      nerve was the most commonly involved nerve in patients with these lesions
      followed by involvement of trigeminal nerve. MRI was erroneous in giving
      provisional diagnosis of schwannoma in one case, which on subsequent surgery and
      histopathology was found to be a meningioma. The sensitivity of MRI for correctly
      diagnosing vestibular schwannoma was 100 % and specificity was 92.86 % with a
      positive predictive value of 94.12 % and accuracy of 96.67 %. MRI is considered
      as an excellent noninvasive investigation for CP angle schwannoma's. It can
      identify the site and extension of the lesions as well as the characteristic
      signal. Apart from diagnosing, MR imaging plays an important role in stratifying
      patients into appropriate treatment options. 

PMID- 25621228
TI  - Sinonasal malignancies: long term follow up after surgical management-an analysis
      of outcomes.
AB  - Sinonasal malignancies are rare and survival analysis in affected patients is
      arduous and perplexing due to various factors. In this review article, attempt
      has been made to overcome some of those factors while analysing survival
      outcomes. AIMS AND OBJECTIVES: The aim of this study was to share the experience
      of a tertiary care centre in the surgical management of sinonasal malignancies
      over 12 years. MATERIALS AND METHODS: This study is a retrospective chart review,
      and in this study, hospital records of 58 patients with biopsy proven sinonasal
      malignancies were studied. Only the patients undergoing primary or salvage
      surgery at our institution from May-2000 to April-2012 with a minimum follow up
      of 2 years were included. Statistical analyses such as means, proportions, Kaplan
      Meier analysis and Cox's regression model were done. RESULTS: Majority of the
      patients were males (n = 43) belonging to fourth and fifth decades. Squamous cell
      carcinoma was the most common (n = 17) histopathological type, followed by
      adenoid cystic carcinoma (n = 14). Majority presented with stage IV disease (n =
      42). 17 patients were operated for recurrent disease. Over all 5 year survival
      was 72 % and disease free survival was 44 %. Separate analysis for epithelial and
      matched non-epithelial group showed poorer prognosis with epithelial group (p =
      0.0120). Multivariate analysis showed histopathological type (epithelial) and
      presence of pathological risk factors (positive margins and/or perineural
      invasion) affecting survival. CONCLUSIONS: Advanced stage presentation is the
      norm for sinonasal malignancies. This study noted a 5 year overall survival of 72
      % and disease free survival of 44 %. Epithelial histopathology carries poorer
      prognosis then other counterparts and incomplete removal is shown to add to poor
      prognosis independently.

PMID- 25621230
TI  - Hearing outcome after type I tympanoplasty: a retrospective study.
AB  - The purpose of this retrospective study was to evaluate the hearing outcomes
      using temporalis fascia graft for tympanic membrane reconstruction in type 1
      tympanoplasty. It included 100 patients with tubotympanic type of chronic
      suppurative otitis media requiring only tympanic membrane reconstruction.
      Patients requiring ossicular reconstruction or with attico antral disease were
      excluded. Patients were assessed after 3, 6 months and 1 year for graft status
      and hearing outcome. Hearing evaluation was done using tuning fork tests and pure
      tone audiometry. In total, 88 out of 100 patients had intact and completely
      healed grafts at 1 year postoperatively (success rate of 88 %). The Hearing gain
      achieved was 14.55 dBs and the mean air bone gap reduction was 11.94 dBs. This
      reduction was statistically significant when compared to the pre operative
      hearing conditions. 

PMID- 25621229
TI  - Relative etiological importance of adenoid hypertrophy versus sinusitis in
      children with persistent rhinorrhoea.
AB  - Persistent rhinorrhoea is a common, yet often neglected, problem among Indian
      children. This study was designed to evaluate the relative etiological importance
      of adenoid hypertrophy versus sinusitis in children with persistent rhinorrhea.
      Additionally, the association between S. pneumoniae colonization and adenoid
      hypertrophy was studied. Children aged 1-14 years with persistent rhinorrhea
      underwent clinical evaluation, rigid nasal endoscopy and xrays of the nasopharynx
      and paranasal sinuses to ascertain the presence of adenoid hypertrophy and
      sinusitis using standard criteria. Nasopharyngeal swabbing to ascertain the
      presence of nasopharyngeal colonization with S. pneumoniae was also performed.
      Adenoid hypertrophy was more consistently associated with persistent rhinorrhea
      than sinusitis (p < 0.0001). Coincident adenoid hypertrophy and sinusitis
      occurred in 57 %. S. pneumoniae was cultured in only 29 % of children. Up to 47 %
      of patients had features of nasal allergy. There was no association between S.
      pneumoniae colonization and adenoid hypertrophy (p = 0.1). Adenoid hypertrophy is
      an important cause of persistent rhinorrhea in children. Measures to evaluate for
      and treat adenoid hypertrophy should be instituted early to alleviate the problem
      of persistent rhinorrhoea in children. S. pneumoniae colonization of the
      nasopharynx is not a major etiological factor for persistent rhinorrhoea in these
      children. Nasal allergy may be a cause of adenoid hypertrophy in roughly half the
      children. 

PMID- 25621231
TI  - Carotid Doppler ultrasound evaluation in patients with pulsatile tinnitus.
AB  - A wide range of conditions, including atherosclerosis, may lead to pulsatile
      tinnitus. The objective of this study was to evaluate the patients with pulsatile
      tinnitus by means of carotid Doppler ultrasound parameters. Thirty-four patients
      with pulsatile tinnitus were enrolled in the study. Internal carotid artery
      intima-media thickness (IMT), blood flow velocities and arterial lumen diameters
      (LD) were measured and compared with the control group. Mean end diastolic
      velocity (EDV) (32.29 +/- 17.22) and IMT (1.06 +/- 0.36) values were
      significantly higher and mean LD (6.69 +/- 1.20) was significantly lower compared
      to the control group. Peak systolic velocity and EDV values were significantly
      higher in patients whose IMT were greater than 1 mm. Pulsatile tinnitus may be
      the first symptom of a severe, life threatening disease. Doppler sonography is a
      noninvasive, safe and easily applicable diagnostic tool for the evaluation of the
      vascular structures, in patients with pulsatile tinnitus. 

PMID- 25621232
TI  - A novel way of trans-septal splint suturing without nasal packing for
      septoplasty.
AB  - Nasal packing has evolved over the years. Though effective in preventing
      postoperative bleeding complications, they are associated with significant
      morbidity and pain. In recent years nasal splints have been used to reduce the
      duration of nasal packs. The aim of this study is to compare the postoperative
      results in 200 nasal surgeries where in nasal packing was replaced by trans
      septal splint suturing. Two hundred cases of septoplasties were prospectively
      studied over a period of 5 years at Adichunchanagiri Institute of Medical
      Sciences. In 100 cases (group A) nasal packing was done postoperatively whereas
      in other 100 (group B) trans-septal splint suturing was done. Post operatively
      patients were followed up in both groups regarding the presence of pain,
      bleeding, crusting and synechiae for a period of 6 months. Two hundred patients
      were prospectively studied over a period of 5 years with a male-female ratio of
      1.35:1 and the mean age was 31. In group A out of 100 patients followed
      postoperatively, ten had mild bleeding on second day after pack removal none of
      which required repacking, 22 patients had mild pain on second and third day, 18
      had moderate crusting on day 4, 12 had synechiae after 2 weeks. In group B, out
      of 100 patients, minimal bleeding was noted in 13 patients on day 1 and 2, mild
      discomfort was noted in the nose in 34 patients till day 7 (day of splint
      removal), crusting was noted in six patients, synechiae was noted in one patient.
      Elimination of pain and discomfort for the patients and absence of complications
      like synechiae. Also the hospital stay is less than with nasal packing.
      Therefore, suturing of the nasal septum with a splint after septoplasty should be
      a preferred alternative to nasal packing. 

PMID- 25621233
TI  - Comparative Study of Endolymphatic Sac Decompression and Vestibular Neurectomy in
      Intractable Meniere's Disease.
AB  - To comparative study the clinical effect of endolymphatic sac decompression
      (ELSD) and vestibular neurectomy (VN) in intractable Meniere's disease (MD). The
      study included 30 MD intractable patients, 21 of which underwent ELSD and nine of
      which were treated by VN via retrosigmoid approach. Follow-up period ranged from
      3 to 6 years. In 21 patients by ELSD, excellent vertigo control and good control
      were noted in 11 patients (52.4 %) and 4 patients (19.0 %), partial control in 4
      and no control in 2 patients. All the 9 patients by VN, vertigo was excellent
      control. ELSD can improve hearing and tinnitus, but VN not. VN can achieve much
      better effect in improving vertigo in intractable MD patients. But relative to
      ELSD, it has much more disadvantages. 

PMID- 25621234
TI  - Comparative study of response through reduction in the size of hypertrophied
      inferior turbinate causing nasal obstruction by different surgical modalities: a
      prospective study.
AB  - Inferior turbinate hypertrophy is one of the major causes of nasal airway
      obstruction. Medical treatment often produces insufficient improvement. In these
      cases, surgical reduction of inferior turbinate can be proposed. Many different
      techniques are currently available. The aim of our study is to prospectively
      evaluate the effectiveness of three techniques i.e., electrocautery, cryotherapy
      and radiofrequency by comparing the response of patients to these three surgical
      modalities of turbinate reduction. A total of 90 patients presenting with nasal
      obstruction with or without allergic symptoms, fulfilling the inclusion and
      exclusion criteria, attending ENT OPD are included in the study. A prospective
      study was conducted on three groups of thirty patients with symptoms and signs of
      nasal obstruction associated with inferior turbinate hypertrophy of more than 3
      months duration. Then the percentage of subjective improvement in nasal airway is
      used to assess treatment outcomes 1week, 1, 3, 6, 9 and 12 months after surgery.
      At the end of 12 months, 56.6 % of patients treated with electrocautery and 56.6
      % of patients treated with cryotherapy showed 75 % improvement in nasal
      obstruction whereas 59.99 % of patients treated with radiofrequency showed 100 %
      improvement. No statistical difference in the amount of improvement in nasal
      obstruction was noted between the three treatment groups at the end of 12 months
      because of relatively small sample size. But clinically radiofrequency showed
      better subjective improvement in nasal obstruction when compared to cryotherapy
      and electrocautery. 

PMID- 25621235
TI  - Meatoplasty in a CWD Procedure Using an Endaural Approach: A Case Series of 31
      Cases.
AB  - A canal wall down, inside outside mastoidectomy requires an adequate meatoplasty
      for a dry outcome of the procedure. For an inside outside CWD procedure an
      endaural route is the best procedure. However the limitation in this approach is
      the meatoplasty. Thirty-one cases of unsafe disease with a sclerotic mastoid were
      taken up for an inside outside mastoidectomy using an endaural route. A procedure
      is described for the creation of a large adequate meatoplasty raising a posterior
      skin flap and removing the conchal cartilage via endaural route and the results
      discussed here. 

PMID- 25621236
TI  - Type of Antifungals: Does it Matter in Empirical Treatment of Otomycosis?
AB  - To evaluate the efficacy of clotrimazole, miconazole and fluconazole in empirical
      treatment of otomycosis in our tertiary care hospital and to appraise possible
      better outcome in otomycosis. Two hundred and ninety five patients who presented
      with clinical otomycosis at our Melmaruvathur Adiparasakthi Institute of medical
      sciences were incorporated in this study. Two hundred and fourteen patients who
      satisfied our criteria were recognized and they were randomly alienated into
      three groups A, B, C. Group A patients were advised to instill clotrimazole ear
      drops by themselves. Miconazole cream instillation were done by our trained
      personal in group B patients. Group C patients were advised to use fluconazole
      ear drops. Patients were educated to keep ear dry and instructed to come for
      evaluation in first and second week after initial visit. A randomized double
      blinded prospective study. In the first week, clotrimazole had a good response
      than miconazole and fluconazole in our patients and in the second week, our
      patients showed a drastic response in patients instilling flucanozole ear drops
      compared to those using micanozole and clotrimazole. This better outcome doesn't
      show statistical significance since p value is 0.882. Clotrimazole drops,
      miconazole cream and Fluconazole drops showed almost same therapeutic efficacy in
      Otomycosis. 

PMID- 25621237
TI  - Efficiency of cryotherapy in avoiding myringotomy closure in rats.
AB  - Myringotomy and ventilation tube placement is an office-based procedure and
      represents the treatment of choice for middle ear effusions and for transtympanic
      drug administration. The aim of our study was to study the efficiency of low
      pressure spray cryotherapy on protraction of patency time of myringotomies in
      rats. Bilateral myringotomies were performed with cold instruments. Afterward,
      one ear in each rat was randomly assigned for liquid nitrogen treatment of the
      perforated eardrum. Myringotomy patency was recorded daily and histological
      analysis of the eardrums was performed. In the myringotomy group patency time was
      4.75 +/- 2.93 days, while in the cryotherapy group was 11.01 +/- 4.87 days. The
      difference is statistically significant: Student t test, p < 0.00001, 95 % CI (
      8.82; -3.67). Moreover, according to Kaplan-Meier method, myringotomy survival is
      significantly longer in the cryotherapy group. The healing processes of the
      cryotreated eardrums last longer and the patency of myringotomy was longer as
      compared to untreated myringotomies. 

PMID- 25621238
TI  - The study of higher origin of facial artery and its surgical significance.
AB  - Facial artery plays a key role in blood supply of the face. Facial artery one of
      the anterior branches of the external carotid artery originates within the
      carotid triangle. Variation in the origin of the facial artery was observed on
      two sides out of 60 sides in 30 cadavers. Facial artery was observed originating
      at the level just below the maxillary artery within the parotid gland. Facial
      artery may originate as linguo-facial trunk or thyro-linguo-facial trunk. Other
      developmental variations have also been described in the literature like,
      agenesis of facial artery, enlarged facial artery, hypoplastic facial artery.
      Variability in situation may complicate the surgery. Therefore maxillofacial
      surgeon, plastic surgeons and head & neck surgeon should be aware of such
      variation. 

PMID- 25621239
TI  - The value of intranasal splints after partial inferior turbinectomy.
AB  - To assess the value of using the intranasal septal splint after partial inferior
      turbinectomy (PIT) surgery. Prospective, randomized comparative study. The study
      was conducted over a period of 2 years from January 2012 to January 2014 at Minia
      University hospital, Minia, Egypt. A total of 100 patients underwent bilateral
      PIT. They were randomly divided into 2 groups. Group A included 50 patients had
      PIT with intranasal splints and group B included 50 patients had PIT without
      splints. A comparison was made between the 2 groups regarding the postoperative
      pain, degree of nasal obstruction and the degree of tissue healing and adhesions
      formation at 2 time points (2 and 4 weeks postoperatively). At 2 weeks
      postoperatively: visual analogue score (VAS) for the pain was 5 in group A versus
      2.1 in group B (P = 0.01), VAS for nasal obstruction was 6 in group A versus 5 in
      group B (P = 0.328), 70 % of patients had good healing in group A versus 24 % in
      group B (P = 0.02). At 4 weeks postoperatively: VAS for the pain was 1.5 in group
      A versus 1.8 in group B (P = 0.423), VAS for nasal obstruction was 7 in group A
      versus 6 in group B (P = 0.353), 80 % of patients had good healing in group A
      versus 54 % in group B (P = 0.03). The use intranasal septal splints after PIT
      without septal surgery can cause increased postoperative pain in the short term
      follow-up period with significant evidence of decreasing rates of intranasal
      adhesions. 

PMID- 25621240
TI  - To assess the efficacy of modality slow motion dynamic video endoscopy of
      eustachian tube in chronic middle ear pathologies.
AB  - Eustachian tube dysfunction (ETD) has a role in chronic otitis media (COM) is a
      well known fact and number of modalities have come up for its assessment-slow
      motion dynamic videoendoscopy (SMDV) being the latest. (i) To find prevalence of
      ETD in COM and (ii) to check the efficacy of SMDV in detecting dysfunction as
      compared to gold standard tympaometry (TYM). It's a prospective analytical study
      with total of 100 patients of chronic otitis media, hence 200 ears were tested
      for ETD by TYM and SMDV. Prevalence of ETD was noted as 35.5 % in COM whereas the
      two testing modalities TYM versus SMDV showed agreement in 161 cases out of the
      200 ears giving a moderate agreement of statistical significance (Kappa test)
      suggesting SMDV to be included in standard of protocol when assessing ETD along
      with TYM. 

PMID- 25621241
TI  - Endonasal Endoscopic Approach in Management of Paediatric CSF Rhinorrhoea Cases.
AB  - Though endoscopic repair has been the proven to be the gold standard for the
      repair of cerebrospinal fluid rhinorrhoea in adult patients, the type of approach
      to be used in paediatric patients especially those below 5 years is still a
      challenge with no clear cut guidelines. The objective of this study was to
      evaluate the efficacy of using endonasal endoscopic approach for treating
      paediatric patients aged less than 5 years diagnosed with cerebrospinal fluid
      rhinorrhoea. This was a retrospective analysis of five cases of paediatric CSF
      rhinorrhoea operated in a tertiary health care centre with an age of less than 5
      years from October 2002 to September 2010. All the five cases treated by
      endoscopic approach have no further complaints of CSF leak or meningitis with a
      follow up period of a minimum period of 6 months. Two cases were further detected
      to have meningocele and meningoencephalocele which was detected preoperatively
      and treated by reduction and excision respectively. The good results obtained by
      endoscopic closure with lack of major complications and the decreased morbidity
      for the patient suggests that the endoscopic approach should be considered the
      first line of approach in pediatric population. But we would warrant a careful
      selection procedure and availability of adequate expertise for this approach to
      avoid complications. 

PMID- 25621242
TI  - Rhinocerebral mucormycosis: a retrospective study.
AB  - Mucormycosis is an acute often fatal infection caused by fungi of family
      mucoracea (Kauffman and Malani Curr Infect Dis Rep 9(6):435-440). The principal
      pathogens in this family are rhizopus, mucor and absidia species. Mucoracea are
      found in soil, decaying vegetation and other organic matter. Mucormycosis is a
      polymorphic disease with diverse clinical manifestation. It is divided into
      rhinocerebral, pulmonary, cutaneous, cardiac, gastrointestinal and disseminated.
      Rhinocerebral mucormycosis the most commonest manifestation of mucormycosis is
      usually a fatal fulminant infection. Rhinocerebral mucormycosis can be further
      divided into rhino-maxillary and rhino-orbito-cerebral. The disease commonly
      occur in diabetics who have ketoacidosis but is also seen in severely debilitated
      or immunosuppressed patients. It has also been reported from otherwise normal
      individuals. Early diagnosis and treatment is mandatory for a successful
      management of this infection. 

PMID- 25621243
TI  - Giant ethmoid mucocele presenting as an orbital mass.
AB  - Mucocele is a benign and expansile cystic lesion lined with respiratory mucosa of
      pseudo stratified columnar epithelium. Mucocele most commonly produces bone
      destruction within the paranasal sinuses. It mostly involves the frontal sinus
      followed by ethmoid and rarely sphenoid and maxillary sinuses. We report a case
      of giant ethmoid mucocele who presented with history of progressive unilateral
      protrusion of eye since 5 years. CT scan revealed a large mucocele of the ethmoid
      sinus with orbital extension on the same side. He was successfully treated with
      endoscopic sinus surgery. 

PMID- 25621244
TI  - Cavernous sinus thrombosis of nasal origin in children.
AB  - Cavernous sinus thrombosis is a rare presentation. Early diagnosis and aggressive
      treatment are required to prevent morbidity and mortality. Nasal infections can
      give rise to serious intracranial complications. Presented here is a case series
      of cavernous sinus thrombosis of nasal septic origin. The purpose of this article
      is to report our experience in pediatric patients with this illness to ascertain
      a clinical course and outcomes for further clinical application. Eight (08) cases
      of nasalseptic origin of cavernous sinus thrombosis ata tertiary care teaching
      hospital in the north India region of India were included in the study. Cases
      presented with various symptoms like headache, proptosis, ophthalmoplegia and
      fever. The patients were investigated by doing High Resolution Computed
      Tomography of nose & PNS and brain with intravenous contrast. The cases were
      treated with intravenous broad spectrum antibiotics. Eight patients less than 16
      years of age (mean age of 11.2 years)diagnosed with cavernous sinus
      thrombophlebitis due to nasal septic focus over the period of 05 years were
      reviewed retrospectively. The predisposing infections and causative
      microorganisms were similar to previous reports in children. A conservative
      management strategy with antibiotics gave a good prognosis in these cases. There
      were no deaths. Early recognition of this condition, the appropriate selection of
      empirical antibiotic therapy, and the awareness of associated complication were
      the key factors leading to excellent outcome. 

PMID- 25621246
TI  - Comparative Study Between Double Layered Repair of Pharyngeal Mucosa Against
      Routine Single Layered Repair in Cases of "Total Laryngectomy with Partial
      Pharyngectomy" in Respect To Formation of Pharyngo-cutaneous Fistula.
AB  - Advanced glottic cancer (T3,N+ & T4) is usually treated in the majority of
      centres by total laryngectomy. Carcinoma of the larynx is one of the very few
      subsets of all cancers which have shown a decrease in the 5 year survival rate
      and this phenomenon has been attributed to a Pharyngo-cutaneous fistula is the
      most common complication after total laryngectomy. Comparative study between
      double layered repair of pharyngeal mucosa against routine single layered repair
      in cases of "total laryngectomy with partial pharyngectomy". All patients with
      the principal procedure of "total laryngectomy with partial pharyngectomy" in
      department of otorhinolaryngology and head-neck surgery, Netaji Subhash Chandra
      Bose Medical College, Jabalpur, Madhya Pradesh, India were included in this
      study. Out of the 20 patients who had undergone total laryngectomy irrespective
      of the type of mucosal repair, 5 (25 %) patients developed pharyngocutaneous
      fistula. Out of the 8 patients, with double layered mucosa repair, 1 (12.5 %)
      patient developed pharyngocutaneous fistula. Out of the 12 patients, with single
      layered mucosa repair, 4 (33 %) patients developed pharyngocutaneous fistula.
      Double layered repair of pharyngeal mucosa is associated with a lower incidence
      of pharyngocutaneous fistula formation and no increased incidence of dysphagia
      after complete radiotherapy as compared to single layered repair. 

PMID- 25621245
TI  - Oral Sex and HPV: Population Based Indications.
AB  - Human pappilloma virus (HPV) is well established in etiology of uterine cervical
      cancers, but its role in head and neck cancer is strongly suggested through many
      epidemiological and laboratory studies. Although HPV-16 induced oropharyngeal
      cancer is a distinct molecular entity, its role at other sub-sites (oral cavity,
      larynx, nasopharynx, hypopharynx) is less well established. Oral sex is
      supposedly the most commonly practiced unnatural sex across the globe and may
      prove to be a potential transmitting link between cancers of the uterine cervix
      and the oropharynx in males particularly in those 10-15% non-smokers. In India
      with the second largest population (higher population density than China) the
      oral sex is likely to be a common 'recreation-tool' amongst the majority (poor)
      and with the concurrent highly prevalent bad cervical/oral hygiene the HPV is
      likely to synergize other carcinogens. Hence in accordance (or coincidently), in
      India the cervical cancer happens to be the commonest cancer amongst females
      while oral/oropharyngeal cancer amongst males. Oral sex as a link between these
      two cancer types, can largely be argued considering a poor level of evidence in
      the existing literature. The modern world has even commercialized oral sex in the
      form of flavored condoms. The inadequate world literature currently is of a low
      level of evidence to conclude such a relationship because no such specific
      prospective study has been carried out and also due to wide (and unpredictable)
      variety of sexual practices, such a relationship can only be speculated. This
      article briefly reviews the existing literature on various modes and population
      based indications for HPV to be implicated in head and neck cancer with reference
      to oral sexual practice. 

PMID- 25621247
TI  - Changing Trends of HIV/AIDS in Otorhinolaryngology with CD4 (+) Count
      Correlation.
AB  - Human immunodeficiency virus (HIV) affects the vital cells of the immune system
      eventually leading to a fall in the cell mediated immunity. As the disease
      progresses CD4 (+) (cluster of differentiation4) cells reduce, therefore is a
      good indicator of the ongoing disease process [1]. HIV infection has myriads of
      disease presentation; the aim of our study was to correlate the
      otorhinolaryngological manifestations with the CD4 (+) counts. A clinical study,
      of 100 HIV positive patients was done from 2008 to 2011. A clinical evaluation
      revealed 76 % incidence of otorhinolaryngological findings. Oropharyngeal
      manifestations were the commonest, seen in 48 %, predominantly oropharyngeal
      candidiasis. Neck nodes were found in 20 % of the patients. 31 % had otological
      manifestations of which retracted tympanic membrane (eustachian tube dysfunction)
      was the commonest. 18 % had nasal symptoms of which rhinosinusitis was the
      commonest being 14 %. The mean CD4 (+) count was below 200 in patients who
      presented with oropharyngeal candidiasis, otitis externa and epistaxis. With the
      use and availability of HAART (Highly active antiretroviral therapy) more and
      more patients with higher CD4 (+) count are presenting with a different spectrum
      of more subtle disease manifestations, with lower incidence of the classical
      diseases like candidiasis. A routine otorhinolaryngological evaluation at every
      visit with high index of suspicion can help in better disease control and give a
      better quality of life. 

PMID- 25621248
TI  - Does AHI Value Enough for Evaluating the Obstructive Sleep Apnea Severity?
AB  - Obstructive sleep apnea/hypopnea syndrome (OSAHS) is an important and more common
      public health problem with increasing incidence. Polysomonography (PSG) is the
      gold standard test in OSAHS diagnosis. Apnea-hypopnea index (AHI) is the main
      parameter of PSG, which is correlated with OSAHS severity. The main complaint of
      OSAHS patients is daytime sleepiness and the Epworth Sleepiness Scale (ESS) used
      for evaluation of disease severity. The correlation of AHI with daytime
      sleepiness and ESS is well known. But there are many patients, which have
      uncorrelated daytime sleepiness with AHI. This data calls this hypothesis; Are
      there any other parameters which may affect daytime sleepiness. 648 patients with
      complaining of snoring and apnea were evaluated by polysomnography and
      anthropometric measurements. The cut-off value of ESS was accepted 10 as an
      indicator of severe daytime sleepiness. Patients were divided to groups with the
      aim of homogenization, according to AHI values. The patients with similar AHI
      values were analyzed according to their ESS scores. BMI and neck circumference
      were elevated in daytime sleepiness patients. The nocturnal hypoxemia markers;
      apnea number/index, maximum duration of apnea, at least SO2 concentration,
      duration of SO2 less than 90 % were much effected in the group of daytime
      sleepiness. Beside the fact that our research, AHI is not enough for predicting
      the daytime sleepiness; anthropometric measurements and the nocturnal hypoxemia
      markers should be evaluated. 

PMID- 25621249
TI  - Histomorphometric study to compare histological changes between oral squamous
      cell carcinoma and apparently normal adjacent oral mucosa.
AB  - Despite the advances in surgery, radiotherapy and chemotherapy the annual death
      for oral squamous cell carcinoma (OSCC) is rising rapidly. The carcinoma has
      propensity to develop in a field of cancerization. Clinically may it be
      apparently normal mucosa (ANM) adjacent to squamous cell carcinoma which harbours
      certain discrete molecular alteration which ultimately reflects in cellular
      morphology. Hence the aim of the study is to assess histomorphometric changes in
      ANM adjacent to OSCC. A prospective study was done on 30 each of histologically
      diagnosed cases OSCC, ANM at least 1 cm away from OSCC, and normal oral mucosa
      (NOM). Cellular and nuclear morphometric measurements were assessed on
      hematoxylin and eosin sections using image analysis software. Statistical
      analysis was done using analysis of variance test and Tukey's post hoc test. The
      present study showed significant changes in cellular and nuclear area in
      superficial and invasive island of OSCC compared to ANM. The basal cells of ANM
      showed significant decrease in cellular and nuclear areas and nuclear cytoplasmic
      ratio when compared to NOM. Histomorphometry definitely can differentiate OSCC
      form ANM and NOM. The basal cells of ANM showed significant alterations in
      cellular area, nuclear area and nuclear cytoplasmic area when compared to NOM
      suggesting change in the field and have high risk of malignant transformation.
      These parameters can be used as indicator of field cancerization. 

PMID- 25621250
TI  - The effect of uvulopalatopharyngoplasty with tonsillectomy in patients with
      obstructive sleep apnea.
AB  - In the current study, we evaluated the effectiveness of uvulopalatopharyngoplasty
      (UPPP) in treatment of patients with obstructive sleep apnea (OSA) syndrome. All
      patients were previously received medical treatment but their symptoms did not
      resolve. A prospective study was conducted in Shahid Sadoughi Hospital in Yazd,
      Iran. Several sleep indices were evaluated using polysomnography (PSG) in all
      patients before performing UPPP and tonsillectomy. All patients were visited 6
      months after surgery and PSG was repeated to assess the efficacy of surgical
      intervention. A total of 48 patients were enrolled and underwent UPPP and
      tonsillectomy. Six months after surgery, significant improvements were observed
      in all indices of sleep (apnea-hypopnea index, respiratory distress index,
      arterial oxygen saturation, and snoring index). The score of daytime sleepiness
      (assessed by Epworth score) was also improved. According to the result of this
      study, using UPPP surgery in patients with OSA can cause symptoms improvement in
      64 % of cases. It seems that Muller's maneuver test has assisted in briefly
      increasing success rate after surgery, though to prove this claim; other studies
      should be designed and performed in a randomized clinical trial. 

PMID- 25621252
TI  - Cordoplasty: a new technique for managing bilateral vocal cord paralysis and its
      comparison with posterior cordotomy and external procedure in a large study
      group.
AB  - To compare the functional results between posterior cordotomy, cordoplasty and
      external procedure in managing bilateral vocal cord paralysis in one of the
      largest published study group. Retrospective and comparative study. 54 patients
      with bilateral vocal cord paralysis who underwent posterior cordotomy (Group-I),
      cordoplasty (Group-II) and external procedure (Group-III) from 2001 to 2013 were
      compared for functional outcomes. Successful decannulation was achieved more in
      Group-I and II than in Group-III. Voice outcome was better in Group-II patients
      compared to other groups. Outcomes of cordoplasty was better than posterior
      cordotomy and external procedures, with acceptable airway and good quality of
      voice. Posterior cordotomy is preferred in patients without tracheostomy and in
      pediatric patients. In patients with tracheostomy or who accept temporary
      tracheostomy, a cordoplasty is preferred for favorable voice. External procedure
      is preferred for patients not fit for general anesthesia. 

PMID- 25621251
TI  - Cervical esophageal perforation: a 10-year clinical experience in north of iran.
AB  - Perforations of the cervical esophagus are infrequent severe conditions
      associated with a high rate of morbidity and mortality if misdiagnosed. The
      diagnosis and management of cervical esophageal perforation remains a challenging
      clinical problem. We aimed to present our experience of the etiology,
      presentation, management and outcome of cervical esophageal perforation in a 10
      years period. In this cross-sectional study, we reviewed the records of all
      patients with a diagnosis of cervical esophageal perforation admitted at the
      teaching Razi Hospital of Rasht, north of Iran, between 2001 and 2011. 26
      patients (15 male) were studied with mean age of 47.6 +/- 13.78 years, a range
      from 10 to 68 years. Only 16 (61.5 %) of patients were referred within 24 h of
      injury. The etiology was iatrogenic in 15 cases (57.69 %), foreign body ingestion
      in 7 cases (26.9 %), and penetrating traumatic injury in 4 cases (15.4 %). The
      common clinical manifestations of perforation were neck pain in 22 cases (84.6
      %), fever in 19 cases (73.1 %), and subcutaneous emphysema in 12 cases (46.2 %).
      Barium and gastrografin swallow were performed in 57.7 and 23.1 % of patients,
      respectively and flexible esophagoscopy was used in 23.06 %. Most of patients
      (65.4 %) were managed by primary repair. Overall, mortality rate was 7.7 %. Our
      study demonstrates that the most common cause of cervical esophageal perforation
      is iatrogenic injury. Clinical suspicion is most important problem. Furthermore,
      Diagnosis is mainly made by Barium and gastrografin swallow. For a successful
      outcome, primary repair is a preferred treatment for most perforation patients. 

PMID- 25621253
TI  - Utility of toluidine blue test in accessing and detecting intra-oral
      malignancies.
AB  - In vivo staining reveals cytological details that might otherwise not be
      apparent. The aim of the study was to test the utility of toluidine blue test in
      detecting various types of malignant and premalignant lesions in early stage.
      Fifty patients with lesion in oral cavity having suspicion of malignancy
      clinically were selected. After subjecting the patients to clinical examination,
      the suspicious lesions were stained with 1 % toluidine blue. The biopsy site was
      selected on the basis of clinical appearance and dye retention and in the sites
      where no retention of the stain occurred, clinical judgment directed the biopsy
      site. The sensitivity of toluidine blue in detecting premalignant or malignant
      lesions was found to be 97.8 % and the over all specificity was found to be 100
      %. The positive predictive value, negative predictive value and diagnostic
      accuracy was reported to be 100, 80 and 90 % respectively. Toluidine Blue
      staining is highly a reliable source for the detection of insitu and invasive
      carcinomas. Staining with this stains is an adjunct to clinical judgment, assist
      in the choice of biopsy site, follow up of premalignant lesions and marginal
      demarcation of the malignant lesions enabling an intervention method to be
      adopted earlier for the disease, which carries a high rate of morbidity and
      mortality. 

PMID- 25621254
TI  - Association of cagA Positive Helicobacter pylori Infection and Laryngeal Squamous
      Cell Carcinoma: A PCR Approach.
AB  - Helicobacter pylori is a gram-negative bacillus causing benign and malignant
      gastric diseases such as gastroesophageal reflux (GER). In larynx, H. pylori
      causes chronic inflammation and mucosal destruction that may lead to malignant
      changes. Although, H. pylori poses several virulence factors, cagA is probably
      the main factor in this regard. To evaluate the role of cagA gene in laryngeal
      squamous cell carcinoma (LSCC), a case-control study was conducted on patients
      with laryngeal complaints during 2010-2012. Seventy-two patients with LSCC (case
      group) and 72 patients without malignancy (control group) were included in the
      study. The H. pylori and cagA factor were assessed in laryngeal specimen of
      patients with PCR technique. 33 % of patients in case group (24 patients) and
      45.8 % (33 patients) of control group were positive for H. pylori. CagA gene was
      present in 13.8 % (10 patients) of case group specimens and 31.9 % (23 patients)
      of control group. This difference was statistically significant with Mantel
      Haenszel statistical test analyses. The results showed that patients with LSCC
      have significantly lower incidence of laryngeal H. pylori infection and cagA
      virulence factor than those without LSCC. Findings from this study support the
      protective effect of H. pylori infection against laryngeal cancer. 

PMID- 25621255
TI  - Sentinel lymph node localization using 1 % isosulfan blue dye in cases of early
      oral cavity and oropharyngeal squamous cell carcinoma.
AB  - To study the use of 1 % isosulfan blue dye in identifying sentinel node,
      sensitivity and specificity of frozen section and predictive value of sentinel
      node in predicting other nodal status in the cases of oral cavity and
      oropharyngeal squamous cell carcinoma. 15 patients of oral cavity and
      oropharyngeal SCC with clinically N0 neck, who required WLE of the primary lesion
      as well as neck dissection as per recommended treatment protocol, were selected
      from OPD. 1 % Isosulfan dye was injected peritumorally intraoperatively after the
      induction of general anaesthesia. Neck dissection was performed and first node
      taking up the blue dye was identified, dissected, removed and was sent for frozen
      section. In two of the 15 cases a sentinel node was identified (sensitivity of
      the technique-13 %). Both the sentinel nodes were positive for presence of
      metastasis on final histopathology (specificity-100 %). However, five cases had
      nodal metastasis on final histopathological examination of the neck dissection
      specimen (sensitivity of sentinel lymph node biopsy-40 %). Frozen section
      examination had a sensitivity and specificity of 100 %. All data was analyzed
      using SPSS 16 software. Use of 1 % Isosulfan Dye for identification of sentinel
      node is a simple and cheap technique, however, it has low sensitivity as compared
      to the use of triple diagnostic procedure consisting of lymphoscintigraphy, per
      op gamma probe localization and using isosulfan dye for sentinel node
      identification. Sentinel lymph node is representative of nodal status and
      correlates well with the final histopathological examination of the dissected
      neck nodes. 

PMID- 25621256
TI  - Clinicopathological review and survival characteristics of adenoid cystic
      carcinoma.
AB  - To study the clinical characters, the outcomes of treatments and the factors
      affecting treatment results of adenoid cystic carcinomas at Shahid Sadoughi
      Hospital and Shahid Ramazanzadeh radiotherapy center, Yazd, Iran. The clinical
      data of 31 patients with adenoid cystic carcinoma of any anatomic site diagnosed
      over an 8 year period (2004-2012), were investigated retrospectively. Data
      regarding patients' characteristics, pathological features and follow-up were
      obtained from patients records. Survival rate, local recurrence and distant
      metastasis were analyzed using Kaplan-Meier method. Prognosis factors were
      analyzed by Log-rank test and Cox regression. The study included31 patients with
      adenoid cystic carcinoma. The mean age at presentation was 50.2 +/- 24.8 years.
      There were 11 (35.5 %) males and 20 (64.5 %) females with a female predilection
      (M:F = 0.55:1). Parotid gland was the most common site (8/31, 25.7 %) followed by
      submandibular gland (7/31, 22.6 %). Perineural invasion was detected in 67.7 % of
      the cases. Positive surgical status was reported in 48.4 % of the specimens.
      Metastasis was detected in 25.8 % of the patients and the most common site of
      distant metastasis was lung. Overall survival rates at 2, 5, and 7 years were 95,
      75, and 57 % respectively. Margin status showed significant effect on survival (P
      value = 0.01). Positive surgical margin is an important factor affecting the
      prognosis of the patients with adenoid cystic carcinoma. Surgery with negative
      surgical margin is the first choice of treatment for the patients with adenoid
      cystic carcinoma. Our findings show that the prognosis of patients with adenoid
      cystic carcinoma in our center is fair. 

PMID- 25621257
TI  - Lipomas of the oral cavity: clinicopathological and immunohistochemical study of
      24 cases and review of the literature.
AB  - Although lipomas are common soft tissue tumors, few cases of lipoma or its
      variants have been reported in the oral cavity. We here described the clinical,
      histological, and immunohistochemical features of 24 cases of oral lipoma
      obtained from medical records at Nagasaki University Hospital between 1977 and
      2010, and also retrospectively reviewed 603 cases of oral lipoma reported in the
      English literatures. The patients examined comprised 11 men and 13 women with a
      mean age of 59 years, ranging from 31 to 90 years. The main sites involved were
      the buccal mucosa (n = 9), followed by the tongue (n = 4), lip and retromolar
      area (n = 3), floor of the mouth (n = 2), and gingiva (n = 1). The mean tumor
      size was 2.0 cm, ranging from 0.2 to 5 cm. Histological analysis revealed 20
      cases of lipoma, 2 cases of fibrolipoma, and one case each of intramuscular
      lipoma and spindle cell lipoma. Twenty-three cases were treated surgically while
      one case underwent biopsy and follow-up. Recurrence was not observed in any case.
      We reviewed the English literatures, and similar results were obtained. In
      immunohistochemical analysis, PCNA and ki-67 expression indices were higher in
      intramuscular lipoma cases than in its variants. Especially, it showed that a
      long time follow-up may be necessary in ki-67 positive cases. 

PMID- 25621258
TI  - Induction chemotherapy followed by radiotherapy in patients with cervical lymph
      node metastases from unknown primary carcinoma.
AB  - Cervical metastases from unknown primary tumors are rare and no clear therapeutic
      options are available. This study was performed to assess the efficacy and safety
      profiles of induction chemotherapy followed radiotherapy in patients with
      cervical lymph node metastases from unknown primary cancer. Patients with
      histological diagnosis of cervical lymph-node metastasis from carcinoma with an
      unknown primary cancer underwent induction chemotherapy followed by radiotherapy.
      All patients had squamous cell carcinoma. Induction chemotherapy consisted of 3-4
      cycles every 3 weeks of docetaxel (day 1.70 mg/m(2)) and cisplatin (day 1.75
      mg/m(2)). Radiation therapy (RT) was started with in 10 weeks of the last cycle
      of chemotherapy, and it was administered 5 days per week. It was given in daily
      fractions of (1.8) Grays (Gy) of 2 Gy and the total dose to the primary tumor was
      70-74 Gy. Neck dissection was reserved for residual disease after definitive
      radiotherapy. Overall survival, recurrent free survival, and locoregional control
      were calculated using the Kaplan-Meier method. Twenty one patients with an
      unknown primary cancer underwent induction chemotherapy and radiotherapy. After
      induction chemotherapy, 6 patients achieved CR and 8 patients achieved PR. The
      overall response rate after radiation, was 90.4 % (19 of 21 patients).
      Neutropenia and infection were the most common grade 3-4 adverse event during
      induction chemotherapy. Mucositis and dermatitis were the most common grade 3-4
      toxicities during radiotherapy. With a median follow-up of 50.6 months, the
      estimated 2 years OS rates were 71 +/- 6 %, respectively. The median OS was 42
      months (95 % confidence interval CI 8-65 months). The recurrent-free survival
      rate at 2 years was 57 %, respectively. In the patients with responder to
      induction chemotherapy, superior relapse free survival and overall survival rate
      observed. No occurrence of primary cancer was observed during the follow-up
      period. Induction chemotherapy followed RT for unknown primary cancer has
      provided good overall and disease-free survival in all the patients with an
      acceptable rate of complications. The use of induction chemotherapy and radiation
      therapy for more advanced disease led to good clinical results with reasonable
      toxicities. 

PMID- 25621259
TI  - Immediate and Long-term Neurocognitive Outcome in Patients with Obstructive Sleep
      Apnea Syndrome After Continuous Positive Airway Pressure Treatment.
AB  - Neurocognitive dysfunction is a major clinical consequence in patients with
      obstructive sleep apnea syndrome (OSAS). The effects of continuous positive
      airway pressure (CPAP) treatment, as the gold standard of treatment in OSAS, on
      this major complication are controversial. The duration and compliance of CPAP
      are thought to be important factors but evidence is lacking. This study is
      designed to evaluate the effects of immediate (one night), long-term (3 months)
      influence and the compliances of CPAP treatment on the neurocognitive function in
      OSAS patients. We enrolled newly diagnosed severe OSAS patients. Neurocognitive
      function test battery, CANTAB (Cambridge Neuropsychological Test Automated
      Battery), was performed before, one night and 3 months of CPAP treatment.
      Patients with CPAP compliance rate >= 70 % and < 50 % were grouped into good and
      poor adherence subjects, respectively. Fourteen patients were enrolled in final
      analyses. Six of them were in poor compliant group. Improvements in attention
      domain were found in all subjects after one-night treatment and maintained till
      three-month follow-up. Additional improvements in some attention performances and
      visual memory performances were gained only after three-month treatment.
      Significant changes of decision-making and response control function were found
      between good and poor compliance groups after three-month treatment. CPAP can
      improve some neurocognitive function at the very first day used. Longer treatment
      of CPAP can additionally improve some other neurocognitive functions. Compliance
      of CPAP has influence on the recovery of neurocognitive functions in patients
      with severe OSAS. 

PMID- 25621260
TI  - Prognostic value of frozen section in t1, t2 carcinoma of oral cavity.
AB  - Complex anatomy of oral cavity makes it difficult for a surgeon to assess margins
      of oral cancer accurately and positive margins compromise loco regional disease
      control, thus surgeon may rely on frozen section assessment for marginal status.
      We discussed the prognostic value of frozen section in early carcinoma of oral
      cavity. 90 patients with pT1 and pT2 oral cavity cancer operated from January
      2010 to December 2011 under single consultant surgeon were retrospectively
      evaluated. Log rank test and multivariate cox regression model was used for
      testing frozen section against the survival and recurrence free status. Survival
      of patients with positive or negative frozen section was significant (p = 0.037),
      Survival of patients with positive or negative histology report was significant
      (p = 0.004), however; prognosis of patients with positive margins despite
      revision under frozen control was poorer to the patients with negative margin.
      Frozen section assessment is accurate but their use in the surgery of oral cavity
      cancer might not improve loco regional disease control or survival when used
      routinely. 

PMID- 25621261
TI  - Pre-decannulation Peristomal Findings in Tracheostomized Cases and Their Effect
      on the Success of Decannulation.
AB  - Decannulating a patient on a tracheostomy is a procedure that has to be dealt
      with vigilantly. This study evaluated both external and telescopic/bronchoscopic
      findings at the peristomal level of subjects being considered for decannulation.
      The patients did not undergo any intervention after above observations and before
      attempting decannulation. Thereafter peristomal findings and their contribution
      towards failure to decannulate were correlated. Thirty subjects were studied
      prospectively, of whom 21 (70 %) demonstrated peristomal complications including
      granulation tissue, ulceration, mucopurulent discharge, suprastomal granulations,
      suprastomal collapse and suprastomal flap. Complications were more common in the
      younger age group (p = 0.007) as well as in tracheostomies of longer duration
      with mean duration >20 months (p = 0.045). However there was no statistically
      significant correlation between the success of decannulation and various
      peristomal findings. Therefore the success of decannulation in a particular case
      cannot always be correctly predicted by peristomal assessment. 

PMID- 25621262
TI  - Prognostic and predictive factors in gingivo buccal complex squamous cell
      carcinoma: role of tumor budding and pattern of invasion.
AB  - Invasive tumor front (ITF) is the deepest three to six cell layers or detached
      tumor cell groups at the advancing edge of the tumor. Tumor budding is defined as
      presence of isolated single cells or small cell clusters scattered in the stroma
      ahead of the ITF and is characteristic of aggressive cancer. It is recognized as
      an adverse prognostic factor in several human cancers like colorectal,
      oesophageal, laryngeal cancers and more recently tongue cancers. However, the
      prognostic value of tumor budding has not been reported in GBCSCC. The aim of our
      study was to evaluate the role of pattern of invasion (POI) at the ITF, Tumor
      budding and other clinicopathological parameters in predicting nodal metastases
      and prognosis in GBCSCC. 33 patients with primary GBCSCC were prospectively
      evaluated at a tertiary care referral centre. Tumor budding and type of POI was
      examined in detail and data documented. Statistical analyses were carried out to
      assess the correlation of tumor budding, POI, and other clinicopathologic
      parameters (stage, grade of the tumor, tumor thickness, PNI, LVI) with nodal
      metastases and predict prognosis. Cox regression was used for both Univariate and
      multivariate analysis. Significant predictors of nodal metastases on Univariate
      analysis were male gender (p = 0.021), smoking (p = 0.046), Tumor budding (p =
      0.014) and diffuse infiltrative/worst POI (p = 0.004), where as on multivariate
      analysis only worst POI was significantly associated with positive lymph nodes (p
      = 0.004). Presence of nodal metastases (p = 0.01) and tumor thickness >5 mm (p =
      0.009) were independent negative prognostic factors on multivariate analysis.
      Significant single risk factor predictive of positive lymph nodes is worst POI in
      GBCSCC. Nodal metastases and >5 mm tumor thickness are independent risk factors
      for disease free survival. 

PMID- 25621263
TI  - Sialolipoma of minor salivary glands: presentation of five cases and review of
      the literature with an epidemiological analyze.
AB  - Sialolipoma is rare benign neoplasm arise from salivary glands (majors and
      minors) characterized by neoplastic adipose tissue with scattered non-neoplastic
      salivary gland acinus. To date 60 cases (including 5 cases reported in the
      present paper) have been reported in scientific literature. This article presents
      5 new cases of sialolipoma affecting minor salivary glands (MiSG) and
      additionally reviews and analyzes the previously published cases to assess
      possible demographical differences between sialolipoma from minor and from major
      salivary glands. CASE REPORTS: 5 cases (3 females; 2 males; age means 63.8
      years), of sialolipoma from MiSG, are reported. 2 of them were located in buccal
      mucosa, 1 in upper lip mucosa, 1 in floor of the mouth and 1 in retromolar area.
      All tumors were composed by neoplastic adipocytes cells interlaced with normal
      salivary gland acinus cover it by a fibrous tissue capsule. Analyzes of
      literature showed that MiSG sialolipoma is most frequent in females over 60 years
      old, therefore and in conclusion this article assess different demographical
      profile of sialolipoma in respect to their topography.

PMID- 25621264
TI  - Affect on survival per increase in each millimeter of tumor depth in tongue
      cancer.
AB  - The critical tumor depth at which the risk of occult metastasis increases in
      tongue cancer has been demonstrated as >=4-5 mm. Conventional T staging might not
      be an accurate predictor for survival in situations wherein infiltrative growth
      pattern is easily overlooked. Thus risk of death associated with increase in
      tumor depth per millimeter might be useful to understand patient's disease status
      during follow up. Historical cohorts of patients with pT1N0 and pT2N0 primary
      squamous cell carcinoma of tongue treated between January 2010 and December 2011
      were selected and analyzed in univariate and multivariate cox-regression model to
      indicate the risk of death associated with an increase in each millimeter of
      tumor depth. The median period of follow up was 34 months. Total 67 patients
      fulfilled the above mentioned criteria, among them 11 patients died by the end of
      study period. The mean (SD) age of the patients studied was 49.7 (12.7) years and
      their age ranged from 21 to 74 years. Among these 66 % (n = 44) were males. In
      the univariate log-rank test, margin status (p = 0.016), t-stage (p = 0.018) and
      increased tumor depth (p < 0.0001) were risk factors for occurrence of death.
      When adjusted for other risk factors in the multivariate cox-regression model,
      per one unit increase of tumor depth (mm) there was 1.07 (95 % CI 0.95, 1.21)
      units increased risk of death. Depth of tumor with increase in each millimeter in
      tongue cancer appears to be associated with risk of death irrespective of
      regional lymphatic spread. 

PMID- 25621265
TI  - Major factors affecting severity of obstructive sleep apnea.
AB  - Computed tomography (CT) has become a common method for evaluating obstructive
      sleep apnea (OSA). The aim of this study was to analyze the relationships between
      CT parameters and clinical parameters in OSA patients to determine major factors
      affecting the severity of OSA. The records of 128 consecutive snoring patients
      (98 males, 30 females) diagnosed with OSA were retrospectively reviewed.
      Polysomnography was performed for each patient. On CT scans, airway areas were
      measured at the level of the hard palate, the soft palate, and the base of the
      tongue. Polysomnographic parameters were compared by gender and age using the
      Mann-Whitney U test. Pearson's correlation coefficient was used to analyze
      relationships between variables and the AHI in each age group. The women were
      significantly older than the men (p < 0.01). The AHI and apnea index were
      significantly higher in men than in women. Stage 1 sleep and rapid eye movement
      sleep were more frequent in men than in women. The area at the base of the tongue
      was significantly smaller in women than in men (p = 0.027). In the 50-60 age
      group, the AHI was significantly higher in men (41.47 +/- 19.67) than in women
      (17.14 +/- 15.63) (p = 0.001). OSA severity varies with age, gender, and upper
      airway area. The OSA prognosis could be improved by evaluating the major factors
      and treating OSA patients according to epidemiological characteristics and
      anatomical structures. 

PMID- 25621266
TI  - Oropharyngeal Dysphagia: neurogenic etiology and manifestation.
AB  - To determine the type, severity and manifestation of dysphagia in patients with
      neurogenic etiology. Clinical documentation was done on the different etiologies,
      its manifestation, assessment findings and management strategies taken for
      patients with neurogenic oropharyngeal dysphagia who were referred for assessment
      and management of dysphagia over a period of three months in a tertiary care
      teaching hospital. Flexible endoscopic examination was done in all the patients.
      The severity of dysphagia in these patients were graded based on Gugging
      Swallowing Screen (GUSS). A total of 53 patients with neurogenic oropharyngeal
      dysphagia were evaluated by an otolaryngologist and a speech language pathologist
      over a period of three months. The grading of severity based on GUSS for these
      patients were done. There were 30 patients with recurrent laryngeal nerve injury
      due to various etiologies, one patient with Neurofibroma-vestibular schwanoma who
      underwent surgical excision, 16 patients with stroke, two patients with traumatic
      brain injury, two patients with Parkinsonism and two patients with myasthenia
      gravis. The manifestation of dysphagia was mainly in the form of prolonged
      masticatory time, oral transit time, and increased number of swallows required
      for each bolus, cricopharyngeal spasms and aspiration. Among the dysphagia
      patients with neurogenic etiology, dysphagia is manifested with a gradual onset
      and is found to have a progressive course in degenerative disorders. Morbidity
      and mortality may be reduced with early identification and management of
      neurogenic dysphagia. 

PMID- 25621267
TI  - Therapeutic outcome after resection of pulmonary metastasis from head and neck
      carcinomas.
AB  - Hematogenous metastasis is the most common form of metastasis in head and neck
      cancer, and reports have described successful resection of pulmonary metastases
      of such cancers. We report treatment outcomes after surgical resection of
      pulmonary metastases of head and neck cancer and identify prognostic factors.
      This clinicopathologic study investigated the clinical records of 16 patients
      with pulmonary metastases of head and neck cancer (excepting cases of thyroid
      cancer) who had undergone metastasectomy at our center during the period 2001
      2012. The mean age of the 16 patients (11 men and 5 women) was 62.1 years. The
      mean interval between completion of successful treatment of the primary tumor and
      detection of pulmonary metastasis was 21 months (range, 6-56 months). All
      patients underwent pulmonary resection. The overall 1-year survival rate was 79.4
      %, and the 2- to 5-year survival rate was 63.2 %. These rates compare favorably
      to those in previous reports on resection of pulmonary metastases. When
      prognostic factors for survival rates were compared, the factors associated with
      a negative prognosis were a disease-free interval of <12 months and partial
      resection of pulmonary metastases. Multivariate analysis did not reveal any
      prognostic factors associated with negative outcomes. Surgical resection of
      pulmonary metastases of head and neck cancer might improve outcomes. 

PMID- 25621268
TI  - Management experience of subglottic stenosis by endoscopic bougie dilatation with
      mitomycin C and review of literature: case series.
AB  - The aim of the study was to examine and analyze the epidemiology and outcome of
      treatment for paediatric acquired subglottic stenosis treated with endoscopic
      bougie dilatation and topical mitomycin C. There were 15 patients identified from
      2008 until 2013. All of them had acquired subglottic stenosis due to history of
      intubation. Majority of the patients had grade III stenosis, with the total of
      seven. Three patients had grade IV; three were grade II and two were grade I. All
      of the patients with severe stenosis (grade III and IV) needed tracheostomy while
      only one in mild stenosis group (grade I and II) required it for prolonged
      ventilation rather than obstruction due to subglottic stenosis. All of them
      underwent direct laryngoscopy under general anesthesia followed by endoscopic
      dilatation with bougie and topical mitomycin C 0.4 mg/ml for 5 min. Aim of
      success in our study was decannulation of tracheostomy or absence of symptoms at
      exertion. We achieved 6 (60 %) successful decannulation out of 10 patients with
      tracheostomy (excluded the patient with tracheostomy in grade I stenosis due to
      prolonged ventilation). As for those without tracheostomy, 3 (75 %) out of 4
      patients were asymptomatic even at exertion. Average number of dilatation was 3.1
      times, with mean duration of 28 min. No complications were reported in our
      series. One patient with grade I stenosis passed away due to severe pneumonia
      unrelated to the stenosis or dilatation, and she did not have any dilatation
      before she passed away. Multiple related risk factors were identified such as
      intubation, prematurity, movement of endotracheal tube, respiratory infection,
      traumatic intubation and gastroesophageal reflux disease. Experience of open
      surgical method was very limited in our centre in Sabah in East Malaysia.
      Endoscopic technique plays an important role in treatment of subglottic stenosis
      with adjunct like mitomycin C possibly booster the successful rate. 

PMID- 25621269
TI  - Treatment and prognosis of deep neck infections.
AB  - Deep neck infections could have serious threats for life of patients, if not
      noticed adequately. Early diagnosis and correct treatment planning can save the
      patient's lives and prevent complications of disease extension and also surgical
      procedures that in some instances may be performed in an emergent situation with
      higher complication rates. Herein, we have studied 815 cases of deep neck
      abscesses and infections with especial consideration to treatment and prognosis.
      In a retrospective case review, we studied 815 cases admitted in our medical
      center from 1998 until the year 2013. Only patients with abscesses or infections
      deeper than superficial layer of deep cervical fascia were included in this
      study, based on the review of their medical records. From 815 cases (485 males
      and 330 females) surgery was indicated and performed in 428 cases and the rest
      were treated medically. In cases with dental infections as the etiologic factor,
      dental procedures were performed as early as possible (extraction in almost all
      cases). Tracheostomy was performed in five cases. All of the patients in medical
      treatment group and most of the surgically managed patients were discharged while
      were stable with relative or complete resolution of their symptoms. One of our
      patients, a 15 year old boy died with symptoms suggestive for mediastinitis and
      air way compromise. Early diagnosis and medical management can be effective in
      treating deep neck infections. Dental infections and also procedures are the
      major cause in our patients, although tonsillitis and peritonsillar abscess also
      were important leading causes with almost equal numbers in our series. Extraction
      of the infected tooth as early as possible while medical treatment is continued
      can be very helpful. In some cases it may be necessary to perform surgical
      exploration of the neck more than once, and finally, malignant neoplasia,
      somewhere in the head and neck should be considered in some cases, as in one of
      our patients with left side submandibular abscess whose underlying disorder was
      tongue SCC with neck metastasis. Prognosis can be excellent in both medically and
      surgically managed groups if started and designed early and promptly. 

PMID- 25621270
TI  - Practicability of submandibular gland in squamous cell carcinomas of oral cavity.
AB  - Current surgical treatment for oral cancers includes wide surgical excision of
      the primary lesion with appropriate neck dissection. Although tumor metastasis to
      the gland is uncommon, submandibular glands are frequently excised as a part of
      neck dissection because of their proximity to the primary lesion and afferent
      lymph nodes. Herein, we have retrospectively investigated the rate of involvement
      of submandibular glands in oral cavity tumors, and discussed the feasibility
      about resection of the submandibular glands. 94 patients undergoing 98
      supraomohyoid neck dissections for oral cavity squamous cell carcinoma from 1st
      May 2010 till 31st May 2014 were retrospectively evaluated. Inclusion criteria
      were histopathologically confirmed squamous cell carcinoma of the oral cavity and
      surgery as the primary treatment modality, consisting of resection of the primary
      lesion with additional neck dissection, including at least one submandibular
      gland. Among the 98 specimens involvement of submandibular gland was seen only in
      3 patients (3.06 %). Submandibular gland involvement was due to direct invasion
      of primary tumors and via the metastatic periglandular lymph nodes. Decision
      regarding excision of the gland should be done during the operation with the help
      of visual examination and frozen sections instead of preoperative planned
      resection. Preserving submandibular gland is both technically as well as
      oncologically feasible and can achieve potential benefit in preserving the
      submandibular salivary flow. 

PMID- 25621271
TI  - Tracheocele presenting with intermittent dysphonia: a case report.
AB  - We report a rare case of tracheocele presenting in an ENT setting. The referral
      was made on the basis of intermittent dysphonia. The aim of this report is to
      document the rare condition of tracheocele on the right side and to help raise
      the level of its awareness among the otolaryngologists. So far approximately
      thirty cases of this condition have been documented in the literature worldwide.
      An emphasis is placed on the mode of presentation and the management issues, as
      early diagnosis is crucial and offers a favorable prognosis. The right sided
      predilection of the swelling is due to anatomical reason and the cause of
      recurrent dysphonia is explained. 

PMID- 25621272
TI  - Papillary carcinoma of thyroid with an unusual presentation.
AB  - Papillary thyroid carcinoma is well known for its low malignant potential and
      good prognosis. The outcome can be fatal in patients with low compliance and
      delayed treatment. Recent advances in ultrasonographic screening and US guided
      fine needle aspiration biopsy has facilitated early diagnosis of papillary
      thyroid carcinomas. This epithelial thyroid tumour accounts for more than 80 % of
      all thyroid tumours. An occult primary carcinoma of thyroid presenting as
      lymphangioma has been reported rarely. We present a case of a 40-year-old female
      patient with huge cystic midline swelling on the right side of the neck mimicking
      lymphangioma on USG. MRI neck showed a cystic mass causing displacement of the
      trachea and arising from Rt lobe of thyroid gland. Hemithyroidectomy was carried
      out and histopathology revealed papillary carcinoma. In patients with neck
      swellings presenting as huge cystic mass the differential diagnosis of Intra
      cystic variant of papillary carcinoma thyroid and metastatic thyroid papillary
      carcinoma must always be considered prior to planning surgery. 

PMID- 25621273
TI  - Congenital fibroepithelial polyp: a case report of difficult airway.
AB  - A 9 month old child presented with a growth in the oropharynx for removal. Only
      complaint was distressed breathing on crying. It turned out to be a case of
      difficult paediatric airway that was managed well. A diagnoses of oesophageal
      fibro-epithelial polyp was made after histopathological examination. 

PMID- 25621274
TI  - Isolated lichen planus of lower lip: a case report.
AB  - Lichen planus is an idiopathic inflammatory condition, which may involve mucosa
      of the oral cavity, gastrointestinal tract, larynx or the cutaneous surface
      either in isolation or in combinations. Mucosal lichen planus is more common than
      the cutaneous variant. Isolated lip involvement is very rare and should be
      differentiated from other similar leukoplakic lesions. We are reporting a rare
      case of oral lichen planus in an elderly male that was exclusively localised to
      the lower lip. 

PMID- 25621275
TI  - Aggressive fibromatosis of head and neck in a child.
AB  - Aggressive fibromatosis is a broad group of benign fibrous tissue proliferations
      of similar microscopic appearance that are intermediate in their biological
      behavior between benign fibrous tissues and fibrosarcomas. They are rare lesions
      accounting for less than 3 % of all soft tissue tumours. Usual site is extremity
      whereas head and neck fibromatosis is a rare occurrence. We present a case of
      aggressive fibromatosis of the infratemporal fossa in a child, which was treated
      by surgical excision with adjuvant hormonal therapy. 

PMID- 25621276
TI  - Unusual parapharyngeal lipoma.
AB  - Lipomas of the parapharyngeal space (PPS) are extremely rare. CT scan and MRI are
      indispensable tools to investigate these hard to access tumors. PPS lipomas are
      confined to either the prestyloid or post styloid compartments. We report an
      unusual parapharyngeal lipoma involving both the compartments of the PPS. 

PMID- 25621277
TI  - Should we stop performing uvulopalatopharyngoplasty?
AB  - Uvulopalatopharyngoplasty (UPPP) is still one of the most frequently performed
      procedures for snoring and obstructive sleep apnea syndrome (OSAS) in adults,
      with unsatisfactory results. In the era of the mini-invasive/conservative
      surgery, considering the increasing attention to the disregulation of the
      peripheral neuromuscular control of the upper airway contributing to pharyngeal
      collapse in OSAS, with the development of sophisticated treatments such as the
      neural stimulation of the upper-airway, which role should be reserved to a
      muscular resective procedure such as UPPP? Being aware of the uncertain results
      and the high postoperative morbidity of UPPP, we believe that we should re
      evaluate the role of these procedures involving the resection of
      palatal/pharyngeal muscles and uvula. 

PMID- 25621278
TI  - Proton Pump Inhibitors: The Culprit for Barrett's Esophagus?

PMID- 25621279
TI  - Microbes in the coral holobiont: partners through evolution, development, and
      ecological interactions.
AB  - In the last two decades, genetic and genomic studies have revealed the
      astonishing diversity and ubiquity of microorganisms. Emergence and expansion of
      the human microbiome project has reshaped our thinking about how microbes control
      host health-not only as pathogens, but also as symbionts. In coral reef
      environments, scientists have begun to examine the role that microorganisms play
      in coral life history. Herein, we review the current literature on coral-microbe
      interactions within the context of their role in evolution, development, and
      ecology. We ask the following questions, first posed by McFall-Ngai et al. (2013)
      in their review of animal evolution, with specific attention to how coral
      microbial interactions may be affected under future environmental conditions: (1)
      How do corals and their microbiome affect each other's genomes? (2) How does
      coral development depend on microbial partners? (3) How is homeostasis maintained
      between corals and their microbial symbionts? (4) How can ecological approaches
      deepen our understanding of the multiple levels of coral-microbial interactions?
      Elucidating the role that microorganisms play in the structure and function of
      the holobiont is essential for understanding how corals maintain homeostasis and
      acclimate to changing environmental conditions. 

PMID- 25621280
TI  - Mathematical modeling provides kinetic details of the human immune response to
      vaccination.
AB  - With major advances in experimental techniques to track antigen-specific immune
      responses many basic questions on the kinetics of virus-specific immunity in
      humans remain unanswered. To gain insights into kinetics of T and B cell
      responses in human volunteers we combined mathematical models and experimental
      data from recent studies employing vaccines against yellow fever and smallpox.
      Yellow fever virus-specific CD8 T cell population expanded slowly with the
      average doubling time of 2 days peaking 2.5 weeks post immunization.
      Interestingly, we found that the peak of the yellow fever-specific CD8 T cell
      response was determined by the rate of T cell proliferation and not by the
      precursor frequency of antigen-specific cells as has been suggested in several
      studies in mice. We also found that while the frequency of virus-specific T cells
      increased slowly, the slow increase could still accurately explain clearance of
      yellow fever virus in the blood. Our additional mathematical model described well
      the kinetics of virus-specific antibody-secreting cell and antibody response to
      vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3
      months post immunization were derived from the population of circulating antibody
      secreting cells. Taken together, our analysis provided novel insights into
      mechanisms by which live vaccines induce immunity to viral infections and
      highlighted challenges of applying methods of mathematical modeling to the
      current, state-of-the-art yet limited immunological data. 

PMID- 25621281
TI  - Long polar fimbriae participates in the induction of neutrophils transepithelial
      migration across intestinal cells infected with enterohemorrhagic E. coli
      O157:H7.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains are causative agents of
      diarrhea and hemorrhagic colitis, both diseases associated with intestinal
      inflammation and cell damage. Several studies have correlated EHEC virulence
      factors to high levels of intestinal pro-inflammatory cytokines and we have
      previously described that the Long polar fimbriae (Lpf) is involved in the
      secretion of interleukin-8 (IL-8) and up-regulation of genes belonging to the NF
      kappaB pathway using non-polarized epithelial intestinal T84 cells. In the
      current study, we evaluated the two EHEC O157 Lpf fimbriae (Lpf1 and Lpf2) for
      their ability to induce intestinal secretion of IL-8 and the activation of IL8,
      CCL20, and ICAM1 genes on polarized T84 cells. We also determined the
      participation of Lpf1 and Lpf2 in transepithelial migration of polymorphonuclear
      neutrophils (PMNs). Polarized T84 cells infected with EHEC revealed that both,
      Lpf1 and Lpf2, were required for the secretion of IL-8 and the induction of IL8,
      CCL20, and ICAM1 genes. Both fimbriae also played a role in the migration of PMNs
      trough the intestinal cells monolayer. Overall, the present work further
      demonstrated that the fimbriae Lpf1 and Lpf2 are important bacterial virulence
      factors that might be involved in the inflammatory responses associated with EHEC
      infections. 

PMID- 25621282
TI  - Whole genome sequencing and analysis reveal insights into the genetic structure,
      diversity and evolutionary relatedness of luxI and luxR homologs in bacteria
      belonging to the Sphingomonadaceae family.
AB  - Here we report the draft genomes and annotation of four N-acyl homoserine lactone
      (AHL)-producing members from the family Sphingomonadaceae. Comparative genomic
      analyses of 62 Sphingomonadaceae genomes were performed to gain insights into the
      distribution of the canonical luxI/R-type quorum sensing (QS) network within this
      family. Forty genomes contained at least one luxR homolog while the genome of
      Sphingobium yanoikuyae B1 contained seven Open Reading Frames (ORFs) that have
      significant homology to that of luxR. Thirty-three genomes contained at least one
      luxI homolog while the genomes of Sphingobium sp. SYK6, Sphingobium japonicum,
      and Sphingobium lactosutens contained four luxI. Using phylogenetic analysis, the
      sphingomonad LuxR homologs formed five distinct clades with two minor clades
      located near the plant associated bacteria (PAB) LuxR solo clade. This work for
      the first time shows that 13 Sphingobium and one Sphingomonas genome(s) contain
      three convergently oriented genes composed of two tandem luxR genes proximal to
      one luxI (luxR-luxR-luxI). Interestingly, luxI solos were identified in two
      Sphingobium species and may represent species that contribute to AHL-based QS
      system by contributing AHL molecules but are unable to perceive AHLs as signals.
      This work provides the most comprehensive description of the luxI/R circuitry and
      genome-based taxonomical description of the available sphingomonad genomes to
      date indicating that the presence of luxR solos and luxI solos are not an
      uncommon feature in members of the Sphingomonadaceae family. 

PMID- 25621283
TI  - Polyethylenimine-mediated expression of transgenes in the acinar cells of rats
      salivary glands in vivo.
AB  - Non viral-mediated transfection of plasmid DNA provides a fast and reliable way
      to express various transgenes in selected cell populations in live animals. Here,
      we show an improvement of a previously published method that is based on
      injecting plasmid DNA into the ductal system of the salivary glands in live rats.
      Specifically, using complexes between plasmid DNA and polyethyleneimine (PEI) we
      show that the expression of the transgenes is directed selectively to the
      salivary acinar cells. PEI does not affect the ability of cells to undergo
      regulated exocytosis, which was one of the main drawbacks of the previous
      methods. Moreover PEI does not affect the proper localization and targeting of
      transfected proteins, as shown for the apical plasma membrane water channel
      aquaporin 5 (AQP5). Overall, this approach, coupled with the use of intravital
      microscopy, permits to conduct localization and functional studies under
      physiological conditions, in a rapid, reliable, and affordable fashion. 

PMID- 25621285
TI  - Dental utilization by children in Hispanic agricultural worker families in
      California.
AB  - BACKGROUND: Agricultural worker families encounter multiple barriers to accessing
      all needed dental care. This study investigated predisposing, enabling, and need
      factors associated with children's past year dental utilization among Hispanic
      agricultural worker families in central California. METHODS: Oral health survey
      and clinical data were collected from families participating in a larger,
      population-based study in 2006-7. Generalized estimating equation logit
      regression assessed effects on a dental visit among children aged 0-17 (n=405).
      Analyses adjusted for clustering of children in the same household. Predisposing
      (sociodemographics), enabling (child's dental insurance, usual source of dental
      care, caregiver past year dental visit, acculturation level, income and
      education), and need (caregiver's oral health rating, perception of cavities, and
      clinically-determined treatment urgency) factors were examined. RESULTS: Half
      (51%) the children had a past year dental visit, while 23% had never been to a
      dentist. In the final model, children were less likely to have a past year dental
      visit if they were foreign-born, male, had caregivers that thought they had
      cavities or were unsure, and if the dentist recommended treatment 'at earliest
      convenience'. Children aged 6-12, with a regular dental care source, and whose
      caregivers had a recent dentist visit were more likely to have a past year dental
      visit. CONCLUSIONS: Children were more likely to have a past year dental visit if
      they had a usual source of dental care (OR =4.78, CI=2.51-9.08), and if the
      caregiver had a past year dental visit (OR=1.88, CI=1.04-3.38). Emphasis should
      be placed on these two modifiable factors to increase children's dental
      utilization.

PMID- 25621284
TI  - Chronic subordination stress induces hyperphagia and disrupts eating behavior in
      mice modeling binge-eating-like disorder.
AB  - BACKGROUND: Eating disorders are associated with physical morbidity and appear to
      have causal factors like stressful life events and negative affect. Binge eating
      disorder (BED) is characterized by eating in a discrete period of time a larger
      than normal amount of food, a sense of lack of control over eating, and marked
      distress. There are still unmet needs for the identification of mechanisms
      regulating excessive eating, which is in part due to the lack of appropriate
      animal models. We developed a naturalistic murine model of subordination stress
      induced hyperphagia associated with the development of obesity. Here we tested
      the hypotheses that the eating responses of subordinate mice recapitulate the BED
      and that limiting hyperphagia could prevent stress-associated metabolic changes.
      METHODS: Adult male mice were exposed to a model of chronic subordination stress
      associated with the automated acquisition of food intake and we performed a
      detailed meal pattern analysis. Additionally, using a pair-feeding protocol was
      test the hypothesis that the manifestation of obesity and the metabolic syndrome
      could be prevented by limiting hyperphagia. RESULTS: The architecture of feeding
      of subordinate mice was disrupted during the stress protocol due to
      disproportionate amount of food ingested at higher rate and with shorter satiety
      ratio than control mice. Subordinate mice hyperphagia was further exacerbated in
      response to either hunger or to the acute application of a social defeat.
      Notably, the obese phenotype but not the fasting hyperglycemia of subordinate
      mice was abrogated by preventing hyperphagia in a pair feeding paradigm.
      CONCLUSION: Overall these results support the validity of our chronic
      subordination stress to model binge eating disorder allowing for the
      determination of the underlying molecular mechanisms and the generation of
      testable predictions for innovative therapies, based on the understanding of the
      regulation and the control of food intake.

PMID- 25621287
TI  - Decision from Models: Generalizing Probability Information to Novel Tasks.
AB  - We investigate a new type of decision under risk where-to succeed-participants
      must generalize their experience in one set of tasks to a novel set of tasks. We
      asked participants to trade distance for reward in a virtual minefield where each
      successive step incurred the same fixed probability of failure (referred to as
      hazard). With constant hazard, the probability of success (the survival function)
      decreases exponentially with path length. On each trial, participants chose
      between a shorter path with smaller reward and a longer (more dangerous) path
      with larger reward. They received feedback in 160 training trials: encountering a
      mine along their chosen path resulted in zero reward and successful completion of
      the path led to the reward associated with the path chosen. They then completed
      600 no-feedback test trials with novel combinations of path length and rewards.
      To maximize expected gain, participants had to learn the correct exponential
      model in training and generalize it to the test conditions. We compared how
      participants discounted reward with increasing path length to the predictions of
      nine choice models including the correct exponential model. The choices of a
      majority of the participants were best accounted for by a model of the correct
      exponential form although with marked overestimation of the hazard rate. The
      decision-from-models paradigm differs from experience-based decision paradigms
      such as decision-from-sampling in the importance assigned to generalizing
      experience-based information to novel tasks. The task itself is representative of
      everyday tasks involving repeated decisions in stochastically invariant
      environments.

PMID- 25621286
TI  - Mtor-Fanconi Anemia DNA Damage Repair Pathway in Cancer.
AB  - mTOR is a serine/threonine kinase and plays a critical role in mammalian cell
      growth, survival, and metabolism. mTOR is present in two cellular complexes:
      mTORC1 and mTORC2. Dysregulation of the mTOR pathway has been related to
      tumorigenesis, poor prognosis and/or chemotherapy resistance in a variety of
      malignancies. Inhibition of mTORC1 by Rapamycin and its analogs has been explored
      to treat a number of tumors. However, the effectiveness of patient response is
      limited and not all patients respond. Second generation of mTOR inhibitors have
      recently been developed to target mTOR kinase activity and to suppress both
      mTORC1 and mTORC2. Dual mTORC1/mTORC2 inhibitors generally are more efficacious
      in preclinical studies and clinical trials. We and others have recently found
      that dual mTORC1/mTORC2 inhibitors sensitize T-cell acute lymphocytic leukemia
      and rhabdomyosarcoma cells to DNA damaging agents by suppression of expression of
      FANCD2 of the Fanconi anemia pathway, an important DNA repair mechanism that is
      associated with drug resistance of multiple types of cancer. This review will
      highlight mTOR and the Fanconi anemia pathway in cancer, with a particular
      attention to our newly discovered connection between mTOR and the Fanconi anemia
      pathway.

PMID- 25621288
TI  - Translational Science Project Team Managers: Qualitative Insights and
      Implications from Current and Previous Postdoctoral Experiences.
AB  - The development of leadership and project management skills is increasingly
      important to the evolution of translational science and team-based endeavors.
      Team science is dependent upon individuals at various stages in their careers,
      inclusive of postdocs. Data from case histories, as well as from interviews with
      current and former postdocs, and those supervising postdocs, indicate six
      essential tasks required of project managers in multidisciplinary translational
      teams, along with eight skill-related themes critical to their success. To
      optimize the opportunities available and to ensure sequential development of team
      project management skills, a life cycle model for the development of
      translational team skills is proposed, ranging from graduate trainees, postdocs,
      assistant professors, and finally to mature scientists. Specific goals,
      challenges and project management roles and tasks are recommended for each stage
      for the life cycle.

PMID- 25621289
TI  - The Effect of D-Tagatose on Fructose Absorption in a Rat Model.
AB  - D-tagatose is in development as a medication for the treatment of type 2
      diabetes. The effect of oral D-tagatose on the absorption of D-fructose was
      assessed when co-administered in this study. In the pilot study, male Sprague
      Dawley rats were fed C14 labeled fructose and glucose concomitantly to establish
      dose levels for the treatment group of rats fed C14 labeled fructose together
      with D-tagatose. Rats were administered 0, 600, 2000, 6000, or 12000 mg/kg of D
      tagatose along with 2000 mg/kg of fructose. Blood samples were taken over 60
      minutes and were assessed using scintillation counting. 600, 2000, and 6000 mg/kg
      of D-tagatose decreased fructose absorption by 1%, 26%, and 30% respectively
      (12000 mg/kg group was stopped short of completion due to intolerance) as
      measured by AUC of scintillation counts. The 600 and 2000 mg/kg of D-tagatose
      groups showed no difference in plasma glucose concentrations compared to placebo
      while a rise in glucose was seen in the 6000 mg/kg of D-tagatose groups. The
      results indicate that D-tagatose may be useful in reducing fructose absorption,
      which could lead to a beneficial outcome.

PMID- 25621290
TI  - Potential Occupational Risks Associated with Pulmonary Toxicity of Carbon
      Nanotubes.
AB  - Given their remarkable properties, carbon nanotubes (CNTs) have made their way
      through various industrial and medicinal applications and the overall production
      of CNTs is expected to grow rapidly in the next few years, thus requiring an
      additional recruitment of workers. However, their unique applications and
      desirable properties are fraught with concerns regarding occupational exposure.
      The concern about worker exposure to CNTs arises from the results of recent
      animal studies. Short-term and sub-chronic exposure studies in rodents have shown
      consistent adverse health effects such as pulmonary inflammation, granulomas,
      fibrosis, genotoxicity and mesothelioma after inhalation or instillation of
      several types of CNTs. Furthermore, physicochemical properties of CNTs such as
      dispersion, functionalization and particle size can significantly affect their
      pulmonary toxicity. Risk estimates from animal studies necessitate implementation
      of protective measures to limit worker exposure to CNTs. Information on workplace
      exposure is very limited, however, studies have reported that CNTs can be
      aerosolized and attain respirable airborne levels during synthesis and processing
      activities in the workplace. Quantitative risk assessments from sub-chronic
      animal studies recommend the health-based need to reduce exposures below the
      recommended exposure limit of 1 ug/m3. Practice of prevention measures including
      the use of engineering controls, personal protective equipment, health
      surveillance program, safe handling and use, as well as worker training can
      significantly minimize worker exposure and improve worker health and safety.

PMID- 25621292
TI  - Achilles' heel of triple negative cancer.

PMID- 25621291
TI  - Chronic Methamphetamine Increases Alpha-Synuclein Protein Levels in the Striatum
      and Hippocampus but not in the Cortex of Juvenile Mice.
AB  - Methamphetamine is the second most widely used illicit drug worldwide. More than
      290 tons of methamphetamine was synthesized in the year 2005 alone, corresponding
      to approximately ~3 billion 100 mg doses of methamphetamine. Drug addicts abuse
      high concentrations of methamphetamine for months and even years. Current reports
      in the literature are consistent with the interpretation that methamphetamine
      induced neuronal injury may render methamphetamine users more susceptible to
      neurodegenerative pathologies. Specifically, chronic exposure to psychostimulants
      is associated with increases in striatal alpha-synuclein expression, a synaptic
      protein implicated in the pathogenesis of neurodegenerative diseases. This raises
      the question whether methamphetamine exposure affects alpha-synuclein levels in
      the brain. In this short report, we examined alpha-synuclein protein and mRNA
      levels in the striatum, hippocampus and cortex of adolescent male mice following
      a neurotoxic regimen of methamphetamine (24mg/kg/daily/14days). We found that
      methamphetamine exposure resulted in a decrease in the monomeric form of alpha
      synuclein (molecular species <19 kDa), while increasing higher molecular weight
      alpha-synuclein species (>19 kDa) in the striatum and hippocampus, but not in the
      cortex. Despite the elevation of high molecular weight alpha-synuclein species
      (>19 kDa), there was no change in the alpha-synuclein mRNA levels in the
      striatum, hippocampus and cortex of mice exposed to methamphetamine. The
      methamphetamine-induced increase in high molecular weight alpha-synuclein protein
      levels might be one of the causal mechanisms or one of the compensatory
      consequences of methamphetamine-mediated neurotoxicity.

PMID- 25621293
TI  - The emerging roles of GPRC5A in diseases.
AB  - The 'Retinoic Acid-Inducible G-protein-coupled receptors' or RAIG are a group
      comprising the four orphan receptors GPRC5A, GPRC5B, GPRC5C and GPRC5D. As the
      name implies, their expression is induced by retinoic acid but beyond that very
      little is known about their function. In recent years, one member, GPRC5A, has
      been receiving increasing attention as it was shown to play important roles in
      human cancers. As a matter of fact, dysregulation of GPRC5A has been associated
      with several cancers including lung cancer, breast cancer, colorectal cancer, and
      pancreatic cancer. Here we review the current state of knowledge about the
      heterogeneity and evolution of GPRC5A, its regulation, its molecular functions,
      and its involvement in human disease. 

PMID- 25621295
TI  - Metabostemness: Metaboloepigenetic reprogramming of cancer stem-cell functions.
AB  - Cancer researchers are currently embarking on one of their field's biggest
      challenges, namely the understanding of how cellular metabolism or certain
      classes of elite metabolites (e.g., oncometabolites) can directly influence
      chromatin structure and the functioning of epi-transcriptional circuits to
      causally drive tumour formation. We here propose that refining the inherent cell
      attractor nature of nuclear reprogramming phenomena by adding the under
      appreciated capacity of metabolism to naturally reshape the Waddingtonian
      landscape's topography provides a new integrative metabolo-epigenetic model of
      the cancer stem cell (CSC) theory. 

PMID- 25621297
TI  - Selumetinib produces a central core of apoptosis in breast cancer bone metastases
      in mice.
AB  - Bone is a common site for metastatic colonization in patients with breast cancer,
      hence the importance of identifying new treatments for this disease. Preclinical
      studies of bone metastases have commonly employed MDA-MB-231 cells that possess
      an activated KRAS allele. While activating RAS mutations are relatively rare in
      human breast cancer, increased RAS-RAF-MEK pathway activity is common in high
      grade breast cancers. To study the consequences of MEK inhibition on bone
      metastases stemming from the intra-cardiac injection of luciferase-expressing MDA
      MB-231 cells in mice, we used the MEK inhibitor AZD6244 (Selumetinib). We found
      that AZD6244 treatment caused decreased tumor bioluminescence that was associated
      with cavitation of the bone metastases, owing to apoptosis of cells specifically
      within the central region of the bone lesions. Hypothesizing that the latter
      effect was due to the increased sensitivity of poorly perfused regions to pro
      apoptotic stimuli, we found that the combination of serum deprivation and AZD6244
      led to dramatic induction pf MDA-MB-231 apoptosis in vitro. Our results suggest
      that MEK inhibition may be a strategy for triggering cell death within the
      hypoperfused, oxygen and nutrient poor regions of tumors with activated RAS
      alleles. 

PMID- 25621296
TI  - WWP2 is overexpressed in human oral cancer, determining tumor size and poor
      prognosis in patients: downregulation of WWP2 inhibits the AKT signaling and
      tumor growth in mice.
AB  - The WW domain containing E3 ubiquitin protein ligase 2 (WWP2) encodes a member of
      the Nedd4 family of E3 ligases, which catalyzes the final step of the
      ubiquitination cascade. WWP2 is involved in tumoral growth with degradation of
      the tumor suppressor phosphatase and tensin homologue deleted on chromosome TEN
      (PTEN). However, little is known about the mechanisms and roles of WWP2 in human
      malignancies including oral squamous cell carcinomas (OSCCs). We found frequent
      WWP2 overexpression in all OSCC-derived cell lines examined that was associated
      with cellular growth by accelerating the cell cycle in the G1 phase via
      degradation of PTEN and activation of the PI3K/AKT signaling pathway. Our in vivo
      data of WWP2 silencing showed dramatic inhibition of tumoral growth with
      increased expression of PTEN. Our 104 primary OSCCs had significantly higher
      expression of WWP2 than their normal counterparts. Moreover, among the clinical
      variables analyzed, enhanced WWP2 expression was correlated with primary tumoral
      size and poor prognosis. These data suggested that WWP2 overexpression
      contributes to neoplastic promotion via the PTEN/PI3K/AKT pathway in OSCCs. WWP2
      is likely to be a biomarker of tumoral progression and prognosis and a potential
      therapeutic target for development of anticancer drugs in OSCCs. 

PMID- 25621294
TI  - Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based
      etiopathogenic perspective and therapeutic approach to an old cancer question.
AB  - Cancer cells acquire an unusual glycolytic behavior relative, to a large extent,
      to their intracellular alkaline pH (pHi). This effect is part of the metabolic
      alterations found in most, if not all, cancer cells to deal with unfavorable
      conditions, mainly hypoxia and low nutrient supply, in order to preserve its
      evolutionary trajectory with the production of lactate after ten steps of
      glycolysis. Thus, cancer cells reprogram their cellular metabolism in a way that
      gives them their evolutionary and thermodynamic advantage. Tumors exist within a
      highly heterogeneous microenvironment and cancer cells survive within any of the
      different habitats that lie within tumors thanks to the overexpression of
      different membrane-bound proton transporters. This creates a highly abnormal and
      selective proton reversal in cancer cells and tissues that is involved in local
      cancer growth and in the metastatic process. Because of this environmental
      heterogeneity, cancer cells within one part of the tumor may have a different
      genotype and phenotype than within another part. This phenomenon has frustrated
      the potential of single-target therapy of this type of reductionist therapeutic
      approach over the last decades. Here, we present a detailed biochemical framework
      on every step of tumor glycolysis and then proposea new paradigm and therapeutic
      strategy based upon the dynamics of the hydrogen ion in cancer cells and tissues
      in order to overcome the old paradigm of one enzyme-one target approach to cancer
      treatment. Finally, a new and integral explanation of the Warburg effect is
      advanced. 

PMID- 25621298
TI  - MDM4 expression as an indicator of TP53 reactivation by combined targeting of
      MDM2 and MDM4 in cancer cells without TP53 mutation.
AB  - MDM2 and MDM4, a structurally related MDM2 homolog, negatively regulates
      expression and functions of TP53 tumor suppressor gene. To explore the precise
      expression patterns and function of MDM2 and MDM4 in wild-type (wt) TP53 cancer
      cells, we analyzed 11 various cancer cell lines with wt TP53. All cell lines
      exhibited deregulated expression of MDM2 and MDM4, and were divided into two
      distinct types; the one expressing high levels of MDM4 and another expressing low
      levels of MDM4. The low MDM4 type expressed higher MDM2 levels than the high MDM4
      type. In cells with high MDM4 expression, knockdown of MDM4 or MDM2 reactivated
      TP53, and simultaneous knockdown of MDM2 and MDM4 synergistically reactivated
      TP53. In contrast, in cells with low MDM4 expression, knockdown of only MDM2
      reactivated TP53. These results suggest that both MDM2 and MDM4 are closely
      involved in TP53 inactivation in cancer cells with high MDM4 expression, whereas
      only MDM2, and not MDM4, is a regulator of TP53 in cells with low MDM4
      expression. MDM4 expression in wt TP53-tumors is a potential indicator for TP53
      reactivation cancer therapy by simultaneous targeting of MDM4 and MDM2. Specific
      knockdown of MDM2 and MDM4 might be applicable for TP53 restoration therapy. 

PMID- 25621299
TI  - Acquired tumor cell resistance to sunitinib causes resistance in a HT-29 human
      colon cancer xenograft mouse model without affecting sunitinib biodistribution or
      the tumor microvasculature.
AB  - Acquired resistance to anti-angiogenic tyrosine kinase inhibitors is an important
      clinical problem in treating various cancers. To what extent acquired resistance
      is determined by microenvironmental host-factors or by tumor cells directly is
      unknown. We previously found that tumor cells can become resistant to sunitinib
      in vitro. Here, we studied to what extent in vitro induced resistance of tumor
      cells determines in vivo resistance to sunitinib. In severe combined
      immunodeficient mice, tumors were established from HT-29 parental colon cancer
      cells (HT-29PAR) or the in vitro induced sunitinib resistant HT-29 cells (HT
      29SUN). Treatment with sunitinib (40mg/kg/day) inhibited tumor growth of HT-29PAR
      tumors by 71+/-5%, while no inhibition of HT-29SUN tumor growth was observed.
      Intratumoral sunitinib concentrations and reduced MVD were similar in both
      groups. Ki67 staining revealed that tumor cell proliferation was significantly
      reduced with 30% in HT-29PAR tumors, but unaffected in HT-29SUN tumors upon
      sunitinib treatment. The lysosomal capacity reflected by LAMP-1 and -2 expression
      was higher in HT-29SUN compared to HT-29PAR tumors indicating an increased
      sequestration of sunitinib in lysosomes of resistant tumors. In conclusion, we
      demonstrate that tumor cells rather than host-factors may play a crucial role in
      acquired resistance to sunitinib in vivo. 

PMID- 25621300
TI  - Cancer driver candidate genes AVL9, DENND5A and NUPL1 contribute to MDCK
      cystogenesis.
AB  - AVL9, DENND5A and NUPL1 are among the cancer driver candidate genes previously
      identified via dog-human comparison, and may function in epithelial cell polarity
      as indicated by bioinformatics analysis. To better understand their cellular
      functions and roles in cancer, we knocked down each gene in MDCKII cells through
      shRNA and performed three-dimensional culture. Compared to the control, the
      knockdown clones developed significantly more abnormal cysts, e.g., cysts with
      the lumen harboring dead and/or live cells, or cysts having multiple lumens.
      Further analysis revealed that abnormalities initiated at the first cell division
      and persisted throughout the entire cystogenesis process. For NUPL1-knockdown
      cells, abnormal cytogenesis largely arose from faulty cell divisions, notably
      monopolar spindles or spindles with poorly separated poles. For AVL9- or DENND5A
      knockdown cells, abnormalities originated from both aberrant intracellular
      trafficking and defective mitosis. Moreover, while all knockdown clones displayed
      an accelerated rate of both cell proliferation and death, only AVL9- and DENND5A
      knockdowns, but not NUPL1-knockdown, promoted cell migration. These observations
      indicate that NUPL1 contributes to bipolar spindle formation, whereas AVL9 and
      DENND5A participate in both intracellular trafficking and cell cycle progression.
      Our study shed lights on these genes' normal cellular functions and on how their
      alteration contributes to carcinogenesis. 

PMID- 25621301
TI  - Cordycepin is a novel chemical suppressor of Epstein-Barr virus replication.
AB  - Cordyceps species are known to produce numerous active components and are used
      for diverse medicinal purposes because of their varied physiological activities,
      including their ability to protect the liver from damage as well as their
      anticancer, antidepressant, anti-inflammatory, hypoglycemic, antimicrobial
      effects. Cordycepin, an adenosine derivative, differs from adenosine in that its
      ribose lacks an oxygen atom at the 3' position. Several research groups have
      reported that cordycepin has antiviral activity against several viruses including
      influenza virus, plant viruses, human immunodeficiency virus(HIV), murine
      leukemia virus, and Epstein-Barr virus (EBV). In this study, we identify the
      epigenetic mechanisms by which cordycepin exerts its anti-gammaherpesvirus
      effects. We show that cordycepin possesses antitumor and antiviral activity
      against gastric carcinoma and EBV, respectively. A comparison of the CD50 values
      of cordycepin and its analogs showed that the lack of a 2'-hydroxyl group in
      cordycepin was critical for its relatively potent cytotoxicity. Cordycepin
      treatment decreased the rate of early apoptosis in SNU719 cells by up to 64%, but
      increased late apoptosis/necrosis by up to 31%. Interestingly, cordycepin
      increased BCL7A methylation in SNU719 cells by up to 58% and decreased
      demethylation by up to 37%. Consistent with these changes in methylation,
      cordycepin treatment significantly downregulated most EBV genes tested. Under the
      same conditions, cordycepin significantly decreased the frequency of Q and F
      promoter usage, and H3K4me3 histone enrichment was significantly reduced at
      several important EBV genomic loci. Extracellular and intracellular EBV genome
      copy numbers were reduced by up to 55% and 30%, respectively, in response to 125
      MUM cordycepin treatment. Finally, cordycepin significantly suppressed the
      transfer of EBV from LCL-EBV-GFP to AGS cells, indicating that EBV infection of
      gastric epithelial cells was inhibited. These results suggest that cordycepin has
      antiviral and antitumor activities against gammaherpesviruses and host cells
      latently infected with virus. 

PMID- 25621302
TI  - Focusing on moving targets through scattering samples.
AB  - Focusing light through scattering media has been a longstanding goal of
      biomedical optics. While wavefront shaping and optical time-reversal techniques
      can in principle be used to focus light across scattering media, achieving this
      within a scattering medium with a noninvasive and efficient reference beacon, or
      guide star, remains an important challenge. Here, we show optical time-reversal
      focusing using a new technique termed Time Reversal by Analysis of Changing
      wavefronts from Kinetic targets (TRACK). By taking the difference between time
      varying scattering fields caused by a moving object and applying optical time
      reversal, light can be focused back to the location previously occupied by the
      object. We demonstrate this approach with discretely moved objects as well as
      with particles in an aqueous flow, and obtain a focal peak-to-background strength
      of 204 in our demonstration experiments. We further demonstrate that the
      generated focus can be used to noninvasively count particles in a flow-cytometry
      configuration-even when the particles are hidden behind a strong diffuser. By
      achieving optical time reversal and focusing noninvasively without any external
      guide stars, using just the intrinsic characteristics of the sample, this work
      paves the way to a range of scattering media imaging applications, including
      underwater and atmospheric focusing as well as noninvasive in vivo flow
      cytometry.

PMID- 25621303
TI  - Linkage to and engagement in HIV care in western Kenya:   an observational study
      using population-based estimates   from home-based counselling and testing.
AB  - BACKGROUND: Few population-based studies exist on the HIV care continuum in sub
      Saharan Africa. We aimed to describe engagement in care in all adults with an
      existing diagnosis of HIV and to assess the time to and predictors of linkage and
      engagement in adults newly diagnosed via home-based counselling and testing
      (HBCT) in a high-prevalence setting in western Kenya. METHODS: Data were derived
      from AMPATH (Academic Model Providing Access to Healthcare), which has provided
      HIV care in western Kenya since 2001 and the HBCT programme, which has been
      operating since 2007. After a widespread HBCT programme in Bunyala subcounty from
      December, 2009, to February, 2011, we reviewed electronic medical records to
      identify uptake of care in individuals (aged 13 years or older) with previously
      known (self-reported) infection and new (identified at HBCT) HIV diagnoses as of
      June 1, 2014. We defined engagement in HIV care as an initial encounter with an
      HIV care provider. We used Cox regression analysis to examine the predictors of
      engagement in care for newly diagnosed individuals. FINDINGS: Of the 3482 adults
      with HIV identified at HBCT, 2122 (61%) had previously been diagnosed with HIV,
      of whom 1778 (84%) had had at least one clinical encounter within AMPATH. 993
      (73%) of the 1360 individuals with new diagnoses at HBCT were registered in the
      electronic medical records, although only 209 (15%) had seen a clinician over a
      median of 3.4 years since diagnosis. The median time to engagement in the newly
      diagnosed individuals was 60 days (IQR 10-411). INTERPRETATION: Creative and
      innovative strategies are needed to support people to engage with care when they
      are newly diagnosed with HIV through population-based case-finding initiatives.
      FUNDING: US President's Emergency Plan for AIDS Relief (PEPFAR), Abbott
      Laboratories, the Purpleville Foundation, the Global Business Coalition, the US
      National Institute of Mental Health, and the Bill & Melinda Gates Foundation.

PMID- 25621304
TI  - Underlying Rationale and Approach to Treat Hypertension in Adolescents by
      Physicians of Different Specialty.
AB  - OBJECTIVE: To describe the underlying clinical decision-making rationale among
      general pediatricians, family physicians, pediatric cardiologists and pediatric
      nephrologists in their approach to an adolescent with hypertension. METHODS: We
      conducted semi-structured phone interviews with a convenience sample of
      physicians from the above-mentioned 4 specialties. Each participant was asked to
      "think aloud" regarding their approach to a hypothetical patient - 12 year old
      boy with persistent hypertension for 6 months. Standardized open-ended questions
      about potential factors that could affect physicians' diagnosis and treatment
      strategies (e.g., patient age) were used. Interviews were audio-recorded;
      transcribed verbatim; transcripts were independently coded by 2 investigators;
      emergent themes identified and inter-coder agreement achieved. Thematic analysis
      was performed based on grounded theory. RESULTS: Nineteen participants included 5
      general pediatricians, 5 pediatric cardiologists, 5 pediatric nephrologists and 4
      family physicians. Five themes emerged: 1) Accuracy of blood pressure measurement
      and hypertension diagnosis, 2) Shift in the epidemiology of pediatric
      hypertension from secondary to primary hypertension, 3) Patient characteristics
      considered in the decision to initiate workup, 4) Obesity-centered choice of
      diagnostic tests and lifestyle modifications, and 5) Variable threshold for
      initiating antihypertensive pharmacotherapy vs. referral to hypertension
      specialists. CONCLUSIONS: There is variation across primary care and specialty
      physicians who provide care for children and adolescents with hypertension. Key
      areas of variability include the willingness to initiate antihypertensive
      medications, the use of diagnostic tests (e.g., ambulatory blood pressure
      monitoring), and the perceived need for specialty referral. Further study is
      needed to assess whether different treatment paradigms result in differential
      patient outcomes.

PMID- 25621305
TI  - Preliminary Examination of Olanzapine and Diet Interactions On Metabolism in a
      Female Macaque.
AB  - Clinical data suggest that atypical antipsychotics such as olanzapine (OLZ)
      induce significant metabolic changes that are serious side effects of their
      primary use. Since controlled human studies are problematic and rodent data may
      be poorly translatable, we have initiated development of a macaque model of OLZ
      induced metabolic disease. In this preliminary feasibility study, we examined
      some metabolic effects of OLZ in a female macaque in the context of a standard
      low-calorie/fat monkey chow diet followed by a high-fat/sugar Western-style diet
      (WSD). A female Japanese macaque was administered OLZ (1.25 mg/day) for 6 months,
      with dietary changes at 2-month intervals as follows: OLZ+Restricted chow,
      OLZ+Unrestricted chow, OLZ+WSD, and placebo+WSD. Weight was assessed weekly.
      Glucose tolerance tests (GTT) and Dexascans were performed at baseline and every
      2 months. Omental (OM) and subcutaneous (SQ) adipose tissue biopsies were
      obtained at baseline, after OLZ+Unrestricted chow and after OLZ+WSD to evaluate
      adipocyte size, lipolysis and insulin-stimulated free fatty acid uptake (FFA). A
      separate trial was conducted on 2 monkeys with 5 days of OLZ- or no-treatment
      followed by RT-PCR on rostral and medial basal hypothalamus. Weight increased on
      OLZ+Restricted chow and stabilized on OLZ+Unrestricted chow. OLZ+WSD did not
      significantly change the weight plateau. Weight declined upon withdrawal of OLZ
      with continued WSD. Body fat increased from 14% at baseline to 22%, 30%, 28% and
      19% at 2, 4, 6 and 8 mo, respectively, indicating that body fat was elevated on
      OLZ regardless of diet and declined upon OLZ removal. Glucose tolerance and the
      insulin response during GTT were normal with OLZ+Restricted chow or
      OLZ+Unrestricted chow. Addition of WSD with OLZ impaired glucose clearance during
      GTT. Insulin remained in the normal range, but first phase insulin secretion was
      reduced. After removal of OLZ, but continued WSD, glucose clearance returned to
      normal, but this was associated with hyperinsulinemia. Adipocyte diameter was
      increased in OM and SQ fat by OLZ+chow and OLZ+WSD to a similar extent. (p<0.01,
      2-way ANOVA). In OM, isoproterenol-stimulated lipolysis occurred at baseline. In
      both depots, isoproterenol-stimulated lipolysis occurred with OLZ+chow, but it
      was significantly blunted by addition of WSD (ANOVA p<0.0001; posthoc p<0.05).
      Insulin increased FFA uptake at baseline. OLZ +chow or OLZ+WSD increased basal
      FFA uptake and insulin-induced FFA uptake was blunted in both depots (posthoc
      p<0.05). There was a marked decrease in POMC gene expression, and increased AgRP
      and NPY expression in the hypothalamus. There was also a clear increase in
      serotonin (5HT) 2C, melanocortin (MCR4), and Leptin (LepR) receptor gene
      expression. These data support the hypotheses that OLZ acts on peripheral tissues
      as well as in the CNS; that changes in hypothalamic gene expression occur very
      rapidly and precede increased fat accumulation; that adipose tissue exhibits
      insulin resistance prior to alterations in GTT; that addition of WSD to OLZ
      precipitates hyperglycemia without an obvious insulin response; and that removal
      of OLZ and continued WSD resulted in normalized glucose clearance and elevated
      insulin. These data suggest complex and early responses to OLZ that may be
      exacerbated by WSD.

PMID- 25621306
TI  - Low-Temperature Trapping of Photointermediates of the Rhodopsin E181Q Mutant.
AB  - Three active-site components in rhodopsin play a key role in the stability and
      function of the protein: 1) the counter-ion residues which stabilize the
      protonated Schiff base, 2) water molecules, and 3) the hydrogen-bonding network.
      The ionizable residue Glu-181, which is involved in an extended hydrogen-bonding
      network with Ser-186, Tyr-268, Tyr-192, and key water molecules within the active
      site of rhodopsin, has been shown to be involved in a complex counter-ion switch
      mechanism with Glu-113 during the photobleaching sequence of the protein. Herein,
      we examine the photobleaching sequence of the E181Q rhodopsin mutant by using
      cryogenic UV-visible spectroscopy to further elucidate the role of Glu-181 during
      photoactivation of the protein. We find that lower temperatures are required to
      trap the early photostationary states of the E181Q mutant compared to native
      rhodopsin. Additionally, a Blue Shifted Intermediate (BSI, lambdamax = 498 nm,
      100 K) is observed after the formation of E181Q Bathorhodopsin (Batho, lambdamax
      = 556 nm, 10 K) but prior to formation of E181Q Lumirhodopsin (Lumi, lambdamax =
      506 nm, 220 K). A potential energy diagram of the observed photointermediates
      suggests the E181Q Batho intermediate has an enthalpy value 7.99 KJ/mol higher
      than E181Q BSI, whereas in rhodopsin, the BSI is 10.02 KJ/mol higher in enthalpy
      than Batho. Thus, the Batho to BSI transition is enthalpically driven in E181Q
      and entropically driven in native rhodopsin. We conclude that the substitution of
      Glu-181 with Gln-181 results in a significant perturbation of the hydrogen
      bonding network within the active site of rhodopsin. In addition, the removal of
      a key electrostatic interaction between the chromophore and the protein
      destabilizes the protein in both the dark state and Batho intermediate
      conformations while having a stabilizing effect on the BSI conformation. The
      observed destabilization upon this substitution further supports that Glu-181 is
      negatively charged in the early intermediates of the photobleaching sequence of
      rhodopsin.

PMID- 25621307
TI  - The Impact of an Infectious Diseases Transition Service on the Care of
      Outpatients on Parenteral Antimicrobial Therapy.
AB  - BACKGROUND: Many hospitalized patients with complicated infections are discharged
      on outpatient parenteral antimicrobial therapy (OPAT). However, little is known
      about how to improve the postdischarge care of OPAT patients. OBJECTIVE: The
      impact of an infectious diseases transitions service (IDTS) on OPAT patient
      readmissions, as well as on processes of care, was evaluated. METHODS: We
      performed a controlled, quasi-experimental evaluation over 15 months in an
      academic medical center. Intervention-arm patients, before and after the
      introduction of an IDTS, were seen by the general infectious diseases consult
      teams, while control-arm patients (discharged on OPAT after hospitalization with
      bacteremia) were not. The IDTS prospectively tracked all OPAT patients and
      coordinated follow-up. The impact of the IDTS was calculated using a differences
      in-differences approach where the interaction between time (before vs after the
      IDTS intervention) and study arm (intervention vs control arm) was the variable
      of interest. The control arm was used only in primary outcome analyses
      (readmissions and emergency department visits). Secondary outcomes included
      process of care measures and non-readmission clinical outcomes. RESULTS: Of 488
      consecutive patients requiring OPAT, 362 were in the intervention arm (215 pre
      intervention and 147 post-intervention) and 126 in the control arm (70 pre
      intervention and 56 post-intervention). Compared to the control arm, the IDTS was
      not associated with changes in 60-day readmissions and/or emergency department
      visits (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI] = 0.13
      1.79). In the intervention arm, implementation of the IDTS was associated with
      fewer antimicrobial therapy errors (OR = 0.062; 95% CI = 0.015-0.262), increased
      laboratory test receipt (OR = 27.85; 95% CI = 12.93-59.99), and improved
      outpatient follow-up (OR = 2.44; 95% CI = 1.50-3.97). CONCLUSIONS: In a
      controlled evaluation, the IDTS did not affect readmissions despite improving
      process of care measures for targeted patients. Care coordination services may
      improve OPAT quality of care, but their relationship to readmissions is unclear.

PMID- 25621308
TI  - Beta Blockade Protection of Bone Marrow Following Injury: A Critical Link between
      Heart Rate and Immunomodulation.
AB  - INTRODUCTION: Severe trauma induces a profound elevation of catecholamines that
      is associated with bone marrow (BM) hematopoietic progenitor cell (HPC) colony
      growth suppression, excessive BM HPC mobilization, and a persistent anemia.
      Previously, propranolol (BB) use after injury and shock has been shown to prevent
      this BM dysfunction and improve hemoglobin levels. This study seeks to further
      investigate the optimal therapeutic dose and timing of BB administration
      following injury and shock. METHODS: Male Sprague-Dawley rats were subjected to a
      combined lung contusion (LC), hemorrhagic shock (HS) model +/- BB. In our dose
      response experiments, animals received BB at 1, 2.5, 5, or 10 mg/kg immediately
      following resuscitation. In our therapeutic window experiments, following LCHS
      rats were given BB immediately, 1 hour, or 3 hours following resuscitation. BM
      and peripheral blood (PB) were collected in all animals to measure cellularity,
      BM HPC growth, circulating HPCs, and plasma G-CSF levels. RESULTS: Propranolol at
      5 and 10 mg/kg significantly reduced HPC mobilization, restored BM cellularity
      and BM HPC growth, and decreased plasma G-CSF levels. Propranolol at 5 and 10
      mg/kg also significantly decreased heart rate. When BB was administered beyond 1
      hour after LCHS, its protective effects on cellularity, BM HPC growth, HPC
      mobilization, and plasma G-CSF levels were greatly diminished. CONCLUSION: Early
      Buse following injury and shock at a dose of at least 5mg/kg is required to
      maintain BM cellularity and HPC growth, prevent HPC mobilization, and reduce
      plasma G-CSF levels. This suggests that propranolol exerts its BM protective
      effect in a dose and time dependent fashion in a rodent model. Finally, heart
      rate may be a valuable clinical marker to assess effective dosing of propranolol.

PMID- 25621309
TI  - Statins and Finasteride Use Differentially Modify the Impact of Metformin on
      Prostate Cancer Incidence in Men with Type 2 Diabetes.
AB  - BACKGROUND: Metformin has shown promise for cancer prevention. Prior studies
      suggested that metformin might interact potential prostate cancer (PCa)
      prevention agents: finasteride and statins. This study assessed if concurrent use
      of statins or finasteride modified the long-term impact of metformin on PCa risk
      in men with type 2 diabetes (T2DM). MATERIALS AND METHODS: The study cohort
      consisted of 71,999 men with T2DM seen in the Veteran Administration Health Care
      System, without prior cancer or liver diseases, nor prescription of
      thiazolidinediones or insulin between FY2003-FY2013. Cox proportional hazard
      analyses (adjusting for covariates and propensity scores of metformin use) were
      conducted to compare the hazard ratio (HR) of PCa associated with metformin use
      between statins or finasteride users and none users. RESULTS: Mean follow-up was
      6.4+/-2.8 years; 5.2% (N= 3,756) of the cohort subsequently received a PCa
      diagnosis. Both statins and finasteride significantly modified the impact of
      metformin on PCa incidence (p-value<0.001): HR's of PCa associated with metformin
      use were 0.89 (p-value=0.02) among non-statin/non-finasteride users, 0.73 (p
      value<0.001) among statin users, and 1.42 (p-value<0.001) among finasteride
      users. CONCLUSION: Metformin was associated with reduced PCa risk in men with
      T2DM. This impact was enhanced by statins but reversed by finasteride. Metformin,
      statins, and finasteride are potential PCa prevention agents. The interaction of
      these drugs on PCa risk needs further confirmation in other cohorts. Our finding
      of differential impacts of metformin, statins, and finasteride (alone or in
      combination) on PCa risk is informative for treatment management in men at risk
      for PCa and T2DM.

PMID- 25621311
TI  - In Vitro Ultrasound Measurements of Powered and Unpowered Total Cavopulmonary
      Connection.
AB  - Three-staged Fontan palliation is performed on children suffering from single
      ventricle congenital heart disease. The series of surgical procedures reroutes
      blood from the vena cavae directly to the pulmonary arteries, creating a total
      cavopulmonary connection (TCPC). A viscous impeller pump (VIP) is currently being
      developed as a cavopulmonary assist device that can modestly augment
      cavopulmonary flow, reduce systemic venous pressure, and improve ventricular
      preload. This study used ultrasound to visualize complex flow patterns in powered
      and unpowered in vitro mock Fontan circulations. The idealized TCPC was modeled
      with a silicone mold and blood analog made of water and glycerol that was seeded
      with 10-MUm glass beads. B-mode, color Doppler, and pulsed-wave Doppler images
      were used to visualize complex flow patterns in the idealized TCPC with (1) no
      VIP, (2) static VIP, and powered VIP rotation rates of (3) 500 and (4) 2,000
      rotations per minute (RPM). Pulsed-wave Doppler data showed higher mean
      velocities and greater variance in the outlets relative to the larger inlets. The
      maximum inlet velocity +/- SD increased from 10.9 +/- 3.53 cm/s with no VIP to
      15.9 +/- 1.03 when the VIP was rotating at 2,000 RPM. Likewise, the maximum
      outlet velocity increased from 14.9 +/- 11.2 cm/s to 18.9 +/- 7.25 cm/s at 2,000
      RPM. The faster mean velocities with the VIP rotating suggest that the pump
      augments cavopulmonary flow. The results of this study suggest that measuring
      complex flow patterns with ultrasound in vivo could be used clinically to
      optimize VIP positioning and rotation rate during and after implantation.

PMID- 25621312
TI  - Learning from a Natural Experiment: Studying a Corporate Work-Time Policy
      Initiative.

PMID- 25621310
TI  - Altered Cholesterol Intracellular Trafficking and the Development of Pathological
      Hallmarks of Sporadic AD.
AB  - Compared to the rare familial early onset Alzheimer's disease (AD) that results
      from gene mutations in AbPP and presenilin-1, the pathogenesis of sporadic AD is
      much more complex and is believed to result from complex interactions between
      nutritional, environmental, epigenetic and genetic factors. Among those factors,
      the presence APOE4 is still the single strongest genetic risk factor for sporadic
      AD. However, the exact underlying mechanism whereby apoE4 contributes to the
      pathogenesis of sporadic AD remains unclear. Here, we discuss how altered
      cholesterol intracellular trafficking as a result of apoE4 might contribute to
      the development of pathological hallmarks of AD including brain deposition of
      amyloid beta (Ab), neurofibrillary tangles, and synaptic dysfunction.

PMID- 25621313
TI  - GUD WIP: Gait-Understanding-Driven Walking-In-Place.
AB  - Many Virtual Environments require walking interfaces to explore virtual worlds
      much larger than available real-world tracked space. We present a model for
      generating virtual locomotion speeds from Walking-In-Place (WIP) inputs based on
      walking biomechanics. By employing gait principles, our model - called Gait
      Understanding-Driven Walking-In-Place (GUD WIP) - creates output speeds which
      better match those evident in Real Walking, and which better respond to
      variations in step frequency, including realistic starting and stopping. The
      speeds output by our implementation demonstrate considerably less within-step
      fluctuation than a good current WIP system - Low-Latency, Continuous-Motion
      (LLCM) WIP - while still remaining responsive to changes in user input. We
      compared resulting speeds from Real Walking, GUD WIP, and LLCM-WIP via user
      study: The average output speeds for Real Walking and GUD WIP respond
      consistently with changing step frequency - LLCM-WIP is far less consistent. GUD
      WIP produces output speeds that are more locally consistent (smooth) and step
      frequency-to-walk-speed consistent than LLCM-WIP.

PMID- 25621314
TI  - Leveraging Social Networks to Detect Anomalous Insider Actions in Collaborative
      Environments.
AB  - Collaborative information systems (CIS) enable users to coordinate efficiently
      over shared tasks. T hey are often deployed in complex dynamic systems that
      provide users with broad access privileges, but also leave the system vulnerable
      to various attacks. Techniques to detect threats originating from beyond the
      system are relatively mature, but methods to detect insider threats are still
      evolving. A promising class of insider threat detection models for CIS focus on
      the communities that manifest between users based on the usage of common subjects
      in the system. However, current methods detect only when a user's aggregate
      behavior is intruding, not when specific actions have deviated from expectation.
      In this paper, we introduce a method called specialized network anomaly detection
      (SNAD) to detect such events. SNAD assembles the community of users that access a
      particular subject and assesses if similarities of the community with and without
      a certain user are sufficiently different. We present a theoretical basis and
      perform an extensive empirical evaluation with the access logs of two distinct
      environments: those of a large electronic health record system (6,015 users,
      130,457 patients and 1,327,500 accesses) and the editing logs of Wikipedia
      (2,388,955 revisors, 55,200 articles and 6,482,780 revisions). We compare SNAD
      with several competing methods and demonstrate it is significantly more
      effective: on average it achieves 20-30% greater area under an ROC curve.

PMID- 25621315
TI  - Short-read, high-throughput sequencing technology for STR genotyping.
AB  - DNA-based methods for human identification principally rely upon genotyping of
      short tandem repeat (STR) loci. Electrophoretic-based techniques for variable
      length classification of STRs are universally utilized, but are limited in that
      they have relatively low throughput and do not yield nucleotide sequence
      information. High-throughput sequencing technology may provide a more powerful
      instrument for human identification, but is not currently validated for forensic
      casework. Here, we present a systematic method to perform high-throughput
      genotyping analysis of the Combined DNA Index System (CODIS) STR loci using short
      read (150 bp) massively parallel sequencing technology. Open source reference
      alignment tools were optimized to evaluate PCR-amplified STR loci using a custom
      designed STR genome reference. Evaluation of this approach demonstrated that the
      13 CODIS STR loci and amelogenin (AMEL) locus could be accurately called from
      individual and mixture samples. Sensitivity analysis showed that as few as 18,500
      reads, aligned to an in silico referenced genome, were required to genotype an
      individual (>99% confidence) for the CODIS loci. The power of this technology was
      further demonstrated by identification of variant alleles containing single
      nucleotide polymorphisms (SNPs) and the development of quantitative measurements
      (reads) for resolving mixed samples.

PMID- 25621316
TI  - Read-mapping using personalized diploid reference genome for RNA sequencing data
      reduced bias for detecting allele-specific expression.
AB  - Next generation sequencing (NGS) technologies have been applied extensively in
      many areas of genetics and genomics research. A fundamental problem when comes to
      analyzing NGS data is mapping short sequencing reads back to the reference
      genome. Most of existing software packages rely on a single uniform reference
      genome and do not automatically take into the consideration of genetic variants.
      On the other hand, large proportions of incorrectly mapped reads affect the
      correct interpretation of the NGS experimental results. As an example, Degner et
      al. showed that detecting allele-specific expression from RNA sequencing data was
      biased toward the reference allele. In this study, we developed a method that
      utilize DirectX 11 enabled graphics processing unit (GPU)'s parallel computing
      power to produces a personalized diploid reference genome based on all known
      genetic variants of that particular individual. We show that using such a
      personalized diploid reference genome can improve mapping accuracy and
      significantly reduce the bias toward reference allele in allele-specific
      expression analysis. Our method can be applied to any individual that has
      genotype information obtained either from array-based genotyping or resequencing.
      Besides the reference genome, no additional changes to alignment algorithm are
      needed for performing read mapping therefore one can utilize any of the existing
      read mapping tools and achieve the improved read mapping result. C++ and GPU
      compute shader source code of the software program is available at:
      http://code.google.com/p/diploid-mapping/downloads/list.

PMID- 25621317
TI  - MODELING OF A NANOPARTICLE MOTION IN A NEWTONIAN FLUID: A COMPARISON BETWEEN
      FLUCTUATING HYDRODYNAMICS AND GENERALIZED LANGEVIN PROCEDURES.
AB  - A direct numerical simulation adopting an arbitrary Lagrangian-Eulerian based
      finite element method is employed to simulate the motion of a nanocarrier in a
      quiescent fluid contained in a cylindrical tube. The nanocarrier is treated as a
      solid sphere. Thermal fluctuations are implemented using two different
      approaches: (1) fluctuating hydrodynamics; (2) generalized Langevin dynamics
      (Mittag-Leffler noise). At thermal equilibrium, the numerical predictions for
      temperature of the nanoparticle, velocity distribution of the particle, decay of
      the velocity autocorrelation function, diffusivity of the particle and particle
      wall interactions are evaluated and compared with analytical results, where
      available. For a neutrally buoyant nanoparticle of 200 nm radius, the comparisons
      between the results obtained from the fluctuating hydrodynamics and the
      generalized Langevin dynamics approaches are provided. Results for particle
      diffusivity predicted by the fluctuating hydrodynamics approach compare very well
      with analytical predictions. Ease of computation of the thermostat is obtained
      with the Langevin approach although the dynamics gets altered.

PMID- 25621318
TI  - Redirected Touching: Training and Adaptation in Warped Virtual Spaces.
AB  - Redirected Touching is a technique in which virtual space is warped to map many
      virtual objects onto one real object that serves as a passive haptic prop. Recent
      work suggests that this mapping can often be predictably unnoticeable and have
      little effect on task performance. We investigated training and adaptation on a
      rapid aiming task in a real environment, an unwarped virtual environment, and a
      warped virtual environment. Participants who experienced a warped virtual space
      reported an initial strange sensation, but adapted to the warped space after
      short repeated exposure. Our data indicate that all the virtual training was less
      effective than real-world training, but after adaptation, participants trained as
      well in a warped virtual space as in an unwarped one.

PMID- 25621319
TI  - Three-Dimensional Spot Detection in Ratiometric Fluorescence Imaging For
      Measurement of Subcellular Organelles.
AB  - Lysosomes are subcellular organelles playing a vital role in the endocytosis
      process of the cell. Lysosomal acidity is an important factor in assuring proper
      functioning of the enzymes within the organelle, and can be assessed by labeling
      the lysosomes with pH-sensitive fluorescence probes. To enhance our understanding
      of the acidification mechanisms, the goal of this work is to develop a method
      that can accurately detect and characterize the acidity of each lysosome captured
      in ratiometric fluorescence images. We present an algorithm that utilizes the h
      dome transformation and reconciles spots detected independently from two
      wavelength channels. We evaluated our algorithm using simulated images for which
      the exact locations were known. The h-dome algorithm achieved an f-score as high
      as 0.890. We also computed the fluorescence ratios from lysosomes in live HeLa
      cell images with known lysosomal pHs. Using leave-one-out cross-validation, we
      demonstrated that the new algorithm was able to achieve much better pH prediction
      accuracy than the conventional method.

PMID- 25621320
TI  - A New Approach of Arc Skeletonization for Tree-Like Objects Using Minimum Cost
      Path.
AB  - Traditional arc skeletonization algorithms using the principle of Blum's
      transform, often, produce unwanted spurious branches due to boundary
      irregularities and digital effects on objects and other artifacts. This paper
      presents a new robust approach of extracting arc skeletons for three-dimensional
      (3-D) elongated fuzzy objects, which avoids spurious branches without requiring
      post-pruning. Starting from a root voxel, the method iteratively expands the
      skeleton by adding a new branch in each iteration that connects the farthest
      voxel to the current skeleton using a minimum-cost geodesic path. The path-cost
      function is formulated using a novel measure of local significance factor defined
      by fuzzy distance transform field, which forces the path to stick to the
      centerline of the object. The algorithm terminates when dilated skeletal branches
      fill the entire object volume or the current farthest voxel fails to generate a
      meaningful branch. Accuracy of the algorithm has been evaluated using computer
      generated blurred and noisy phantoms with known skeletons. Performance of the
      method in terms of false and missing skeletal branches, as defined by human
      expert, has been examined using in vivo CT imaging of human intrathoracic
      airways. Experimental results from both experiments have established the
      superiority of the new method as compared to a widely used conventional method in
      terms of accuracy of medialness as well as robustness of true and false skeletal
      branches.

PMID- 25621321
TI  - Provenance Context Entity (PaCE): Scalable Provenance Tracking for Scientific RDF
      Data.
AB  - The Resource Description Framework (RDF) format is being used by a large number
      of scientific applications to store and disseminate their datasets. The
      provenance information, describing the source or lineage of the datasets, is
      playing an increasingly significant role in ensuring data quality, computing
      trust value of the datasets, and ranking query results. Current provenance
      tracking approaches using the RDF reification vocabulary suffer from a number of
      known issues, including lack of formal semantics, use of blank nodes, and
      application-dependent interpretation of reified RDF triples. In this paper, we
      introduce a new approach called Provenance Context Entity (PaCE) that uses the
      notion of provenance context to create provenance-aware RDF triples. We also
      define the formal semantics of PaCE through a simple extension of the existing
      RDF(S) semantics that ensures compatibility of PaCE with existing Semantic Web
      tools and implementations. We have implemented the PaCE approach in the
      Biomedical Knowledge Repository (BKR) project at the US National Library of
      Medicine. The evaluations demonstrate a minimum of 49% reduction in total number
      of provenance-specific RDF triples generated using the PaCE approach as compared
      to RDF reification. In addition, performance for complex queries improves by
      three orders of magnitude and remains comparable to the RDF reification approach
      for simpler provenance queries.

PMID- 25621322
TI  - A Bayesian Approach to Distinguishing Interdigitated Muscles in the Tongue from
      Limited Diffusion Weighted Imaging.
AB  - Fiber tracking in crossing regions is a well known issue in diffusion tensor
      imaging (DTI). Multi-tensor models have been proposed to cope with the issue.
      However, in cases where only a limited number of gradient directions can be
      acquired, for example in the tongue, the multi-tensor models fail to resolve the
      crossing correctly due to insufficient information. In this work, we address this
      challenge by using a fixed tensor basis and incorporating prior directional
      knowledge. Within a maximum a posteriori (MAP) framework, sparsity of the basis
      and prior directional knowledge are incorporated in the prior distribution, and
      data fidelity is encoded in the likelihood term. An objective function can then
      be obtained and solved using a noise-aware weighted l1-norm minimization.
      Experiments on a digital phantom and in vivo tongue diffusion data demonstrate
      that the proposed method is able to resolve crossing fibers with limited gradient
      directions.

PMID- 25621324
TI  - Proceedings B: moving forward to meet new challenges.

PMID- 25621323
TI  - 1. Alternative splicing of viral receptors: A review of the diverse morphologies
      and physiologies of adenoviral receptors.
AB  - Understanding the biology of cell surface proteins is important particularly when
      they are utilized as viral receptors for viral entry. By manipulating the
      expression of cell surface receptors that have been coopted by viruses, the
      susceptibility of an individual to virus-induced disease or, alternatively, the
      effectiveness of viral-based gene therapy can be modified. The most commonly
      studied vector for gene therapy is adenovirus. The majority of adenovirus types
      utilize the coxsackievirus and adenovirus receptor (CAR) as a primary receptor to
      enter cells. Species B adenovirus do not interact with CAR, but instead interact
      with the cell surface proteins desmoglein-2 (DSG-2) and cluster of
      differentiation 46 (CD46). These cell surface proteins exhibit varying degrees of
      alternative mRNA splicing, creating an estimated 20 distinct protein isoforms. It
      is likely that alternative splice forms have allowed these proteins to optimize
      their effectiveness in a plethora of niches, including roles as cell adhesion
      proteins and regulators of the innate immune system. Interestingly, there are
      soluble isoforms of these viral receptors, which lack the transmembrane domain.
      These soluble isoforms can potentially bind to the surface of a virus in the
      extracellular compartment, blocking the ability of the virus to bind to the host
      cell, reducing viral infectivity. Finally, the diversity of viral receptor
      isoforms appears to facilitate an assortment of interactions between viral
      receptor proteins and cytosolic proteins, leading to differential sorting in
      polarized cells. Using adenoviral receptors as a model system, the purpose of
      this review is to highlight the role that isoform-specific protein localization
      plays in the entry of pathogenic viruses from the apical surface of polarized
      epithelial cells.

PMID- 25621325
TI  - Maternal and genetic factors determine early life telomere length.
AB  - In a broad range of species--including humans--it has been demonstrated that
      telomere length declines throughout life and that it may be involved in cell and
      organismal senescence. This potential link to ageing and thus to fitness has
      triggered recent interest in understanding how variation in telomere length is
      inherited and maintained. However, previous studies suffer from two main
      drawbacks that limit the possibility of understanding the relative importance of
      genetic, parental and environmental influences on telomere length variation.
      These studies have been based on (i) telomere lengths measured at different time
      points in different individuals, despite the fact that telomere length changes
      over life, and (ii) parent-offspring regression techniques, which do not enable
      differentiation between genetic and parental components of inheritance. To
      overcome these drawbacks, in our study of a songbird, the great reed warbler, we
      have analysed telomere length measured early in life in both parents and
      offspring and applied statistical models (so-called 'animal models') that are
      based on long-term pedigree data. Our results showed a significant heritability
      of telomere length on the maternal but not on the paternal side, and that the
      mother's age was positively correlated with their offspring's telomere length.
      Furthermore, the pedigree-based analyses revealed a significant heritability and
      an equally large maternal effect. Our study demonstrates strong maternal
      influence on telomere length and future studies now need to elucidate possible
      underlying factors, including which types of maternal effects are involved.

PMID- 25621326
TI  - Dispersal and the transition to sympatry in vertebrates.
AB  - Under allopatric speciation models, a key step in the build-up of species
      richness is population dispersal leading to the co-occurrence of previously
      geographically isolated forms. Despite its central importance for community
      assembly, the extent to which the transition from spatial segregation (allopatry
      or parapatry) to coexistence (sympatry) is a predictable process, or
      alternatively one governed by chance and the vagaries of biogeographic history,
      remains poorly understood. Here, we use estimated divergence times and current
      patterns of geographical range overlap among sister species to explore the
      evolution of sympatry in vertebrates. We show that rates of transition to
      sympatry vary predictably according to ecology, being faster in marine or
      strongly dispersive terrestrial clades. This association with organism vagility
      is robust to the relative frequency of geographical speciation modes and
      consistent across taxonomic scales and metrics of dispersal ability. These
      findings reject neutral models of dispersal assembly based simply on evolutionary
      age and are not predicted by the main alternative view that range overlap is
      primarily constrained by biotic interactions. We conclude that species
      differences in dispersal limitation are fundamental in organizing the assembly of
      ecological communities and shaping broad-scale patterns of biodiversity over
      space and time.

PMID- 25621327
TI  - Long sperm fertilize more eggs in a bird.
AB  - Sperm competition, in which the ejaculates of multiple males compete to fertilize
      a female's ova, results in strong selection on sperm traits. Although sperm size
      and swimming velocity are known to independently affect fertilization success in
      certain species, exploring the relationship between sperm length, swimming
      velocity and fertilization success still remains a challenge. Here, we use the
      zebra finch (Taeniopygia guttata), where sperm size influences sperm swimming
      velocity, to determine the effect of sperm total length on fertilization success.
      Sperm competition experiments, in which pairs of males whose sperm differed only
      in length and swimming speed, revealed that males producing long sperm were more
      successful in terms of (i) the number of sperm reaching the ova and (ii)
      fertilizing those ova. Our results reveal that although sperm length is the main
      factor determining the outcome of sperm competition, complex interactions between
      male and female reproductive traits may also be important. The mechanisms
      underlying these interactions are poorly understood, but we suggest that
      differences in sperm storage and utilization by females may contribute to the
      outcome of sperm competition.

PMID- 25621328
TI  - You are what you eat: diet-induced chemical crypsis in a coral-feeding reef fish.
AB  - The vast majority of research into the mechanisms of camouflage has focused on
      forms that confound visual perception. However, many organisms primarily interact
      with their surroundings using chemosensory systems and may have evolved
      mechanisms to 'blend in' with chemical components of their habitat. One potential
      mechanism is 'chemical crypsis' via the sequestration of dietary elements,
      causing a consumer's odour to chemically match that of its prey. Here, we test
      the potential for chemical crypsis in the coral-feeding filefish, Oxymonacanthus
      longirostris, by examining olfactory discrimination in obligate coral-dwelling
      crabs and a predatory cod. The crabs, which inhabit the corals consumed by O.
      longirostris, were used as a bioassay to determine the effect of coral diet on
      fish odour. Crabs preferred the odour of filefish fed their preferred coral over
      the odour of filefish fed a non-preferred coral, suggesting coral-specific
      dietary elements that influence odour are sequestered. Crabs also exhibited a
      similar preference for the odour of filefish fed their preferred coral and odour
      directly from that coral, suggesting a close chemical match. In behavioural
      trials, predatory cod were less attracted to filefish odour when presented
      alongside the coral it had been fed on, suggesting diet can reduce detectability.
      This is, we believe, the first evidence of diet-induced chemical crypsis in a
      vertebrate.

PMID- 25621329
TI  - Concurrent modulation of neuronal and behavioural olfactory responses to sex and
      host plant cues in a male moth.
AB  - Mating has profound effects on animal physiology and behaviour, not only in
      females but also in males, which we show here for olfactory responses. In cotton
      leafworm moths, Spodoptera littoralis, odour-mediated attraction to sex pheromone
      and plant volatiles are modulated after mating, producing a behavioural response
      that matches the physiological condition of the male insect. Unmated males are
      attracted by upwind flight to sex pheromone released by calling females, as well
      as to volatiles of lilac flowers and green leaves of the host plant cotton,
      signalling adult food and mating sites, respectively. Mating temporarily
      abolishes male attraction to females and host plant odour, but does not diminish
      attraction to flowers. This behavioural modulation is correlated with a response
      modulation in the olfactory system, as shown by electro-physiological recordings
      from antennae and by functional imaging of the antennal lobe, using natural
      odours and synthetic compounds. An effect of mating on the olfactory responses to
      pheromone and cotton plant volatiles but not to lilac flowers indicates the
      presence of functionally independent neural circuits within the olfactory system.
      Our results indicate that these circuits interconnect and weigh perception of
      social and habitat odour signals to generate appropriate behavioural responses
      according to mating state.

PMID- 25621330
TI  - Spatially heterogeneous impact of climate change on small mammals of montane
      California.
AB  - Resurveys of historical collecting localities have revealed range shifts,
      primarily leading edge expansions, which have been attributed to global warming.
      However, there have been few spatially replicated community-scale resurveys
      testing whether species' responses are spatially consistent. Here we repeated
      early twentieth century surveys of small mammals along elevational gradients in
      northern, central and southern regions of montane California. Of the 34 species
      we analysed, 25 shifted their ranges upslope or downslope in at least one region.
      However, two-thirds of ranges in the three regions remained stable at one or both
      elevational limits and none of the 22 species found in all three regions shifted
      both their upper and lower limits in the same direction in all regions. When
      shifts occurred, high-elevation species typically contracted their lower limits
      upslope, whereas low-elevation species had heterogeneous responses. For high
      elevation species, site-specific change in temperature better predicted the
      direction of shifts than change in precipitation, whereas the direction of shifts
      by low-elevation species was unpredictable by temperature or precipitation. While
      our results support previous findings of primarily upslope shifts in montane
      species, they also highlight the degree to which the responses of individual
      species vary across geographically replicated landscapes.

PMID- 25621331
TI  - Does early learning drive ecological divergence during speciation processes in
      parasitoid wasps?
AB  - Central to the concept of ecological speciation is the evolution of ecotypes,
      i.e. groups of individuals occupying different ecological niches. However, the
      mechanisms behind the first step of separation, the switch of individuals into
      new niches, are unclear. One long-standing hypothesis, which was proposed for
      insects but never tested, is that early learning causes new ecological
      preferences, leading to a switch into a new niche within one generation. Here, we
      show that a host switch occurred within a parasitoid wasp, which is associated
      with the ability for early learning and the splitting into separate lineages
      during speciation. Lariophagus distinguendus consists of two genetically distinct
      lineages, most likely representing different species. One attacks drugstore
      beetle larvae (Stegobium paniceum (L.)), which were probably the ancestral host
      of both lineages. The drugstore beetle lineage has an innate host preference that
      cannot be altered by experience. In contrast, the second lineage is found on
      Sitophilus weevils as hosts and changes its preference by early learning. We
      conclude that a host switch has occurred in the ancestor of the second lineage,
      which must have been enabled by early learning. Because early learning is
      widespread in insects, it might have facilitated ecological divergence and
      associated speciation in this hyperdiverse group.

PMID- 25621332
TI  - Stable isotope analysis of vertebrae reveals ontogenetic changes in habitat in an
      endothermic pelagic shark.
AB  - Ontogenetic changes in habitat are driven by shifting life-history requirements
      and play an important role in population dynamics. However, large portions of the
      life history of many pelagic species are still poorly understood or unknown. We
      used a novel combination of stable isotope analysis of vertebral annuli, Bayesian
      mixing models, isoscapes and electronic tag data to reconstruct ontogenetic
      patterns of habitat and resource use in a pelagic apex predator, the salmon shark
      (Lamna ditropis). Results identified the North Pacific Transition Zone as the
      major nursery area for salmon sharks and revealed an ontogenetic shift around the
      age of maturity from oceanic to increased use of neritic habitats. The nursery
      habitat may reflect trade-offs between prey availability, predation pressure and
      thermal constraints on juvenile endothermic sharks. The ontogenetic shift in
      habitat coincided with a reduction of isotopic niche, possibly reflecting
      specialization upon particular prey or habitats. Using tagging data to inform
      Bayesian isotopic mixing models revealed that adult sharks primarily use neritic
      habitats of Alaska yet receive a trophic subsidy from oceanic habitats.
      Integrating the multiple methods used here provides a powerful approach to
      retrospectively study the ecology and life history of migratory species
      throughout their ontogeny.

PMID- 25621333
TI  - Diversification practices reduce organic to conventional yield gap.
AB  - Agriculture today places great strains on biodiversity, soils, water and the
      atmosphere, and these strains will be exacerbated if current trends in population
      growth, meat and energy consumption, and food waste continue. Thus, farming
      systems that are both highly productive and minimize environmental harms are
      critically needed. How organic agriculture may contribute to world food
      production has been subject to vigorous debate over the past decade. Here, we
      revisit this topic comparing organic and conventional yields with a new meta
      dataset three times larger than previously used (115 studies containing more than
      1000 observations) and a new hierarchical analytical framework that can better
      account for the heterogeneity and structure in the data. We find organic yields
      are only 19.2% (+/-3.7%) lower than conventional yields, a smaller yield gap than
      previous estimates. More importantly, we find entirely different effects of crop
      types and management practices on the yield gap compared with previous studies.
      For example, we found no significant differences in yields for leguminous versus
      non-leguminous crops, perennials versus annuals or developed versus developing
      countries. Instead, we found the novel result that two agricultural
      diversification practices, multi-cropping and crop rotations, substantially
      reduce the yield gap (to 9 +/- 4% and 8 +/- 5%, respectively) when the methods
      were applied in only organic systems. These promising results, based on robust
      analysis of a larger meta-dataset, suggest that appropriate investment in
      agroecological research to improve organic management systems could greatly
      reduce or eliminate the yield gap for some crops or regions.

PMID- 25621334
TI  - Culled males, infant mortality and reproductive success in a pre-industrial
      Finnish population.
AB  - Theoretical and empirical literature asserts that the sex ratio (i.e. M/F) at
      birth gauges the strength of selection in utero and cohort quality of males that
      survive to birth. We report the first individual-level test in humans, using
      detailed life-history data, of the 'culled cohort' hypothesis that males born to
      low annual sex ratio cohorts show lower than expected infant mortality and
      greater than expected lifetime reproductive success. We applied time-series and
      structural equation methods to a unique multigenerational dataset of a natural
      fertility population in nineteenth century Finland. We find that, consistent with
      culled cohorts, a 1 s.d. decline in the annual cohort sex ratio precedes an 8%
      decrease in the risk of male infant mortality. Males born to lower cohort sex
      ratios also successfully raised 4% more offspring to reproductive age than did
      males born to higher cohort sex ratios. The offspring result, however, falls just
      outside conventional levels of statistical significance. In historical Finland,
      the cohort sex ratio gauges selection against males in utero and predicts male
      infant mortality. The reproductive success findings, however, provide weak
      support for an evolutionarily adaptive explanation of male culling in utero.

PMID- 25621335
TI  - Ecology has contrasting effects on genetic variation within species versus rates
      of molecular evolution across species in water beetles.
AB  - Comparative analysis is a potentially powerful approach to study the effects of
      ecological traits on genetic variation and rate of evolution across species.
      However, the lack of suitable datasets means that comparative studies of
      correlates of genetic traits across an entire clade have been rare. Here, we use
      a large DNA-barcode dataset (5062 sequences) of water beetles to test the effects
      of species ecology and geographical distribution on genetic variation within
      species and rates of molecular evolution across species. We investigated species
      traits predicted to influence their genetic characteristics, such as surrogate
      measures of species population size, latitudinal distribution and habitat types,
      taking phylogeny into account. Genetic variation of cytochrome oxidase I in water
      beetles was positively correlated with occupancy (numbers of sites of species
      presence) and negatively with latitude, whereas substitution rates across species
      depended mainly on habitat types, and running water specialists had the highest
      rate. These results are consistent with theoretical predictions from nearly
      neutral theories of evolution, and suggest that the comparative analysis using
      large databases can give insights into correlates of genetic variation and
      molecular evolution.

PMID- 25621336
TI  - Effects of bottom trawling on fish foraging and feeding.
AB  - The effects of bottom trawling on benthic invertebrates include reductions of
      biomass, diversity and body size. These changes may negatively affect prey
      availability for demersal fishes, potentially leading to reduced food intake,
      body condition and yield of fishes in chronically trawled areas. Here, the effect
      of trawling on the prey availability and diet of two commercially important
      flatfish species, plaice (Pleuronectes platessa) and dab (Limanda limanda), was
      investigated over a trawling intensity gradient in the Irish Sea. Previous work
      in this area has shown that trawling negatively affects the condition of plaice
      but not of dab. This study showed that reductions in local prey availability did
      not result in reduced feeding of fish. As trawling frequency increased, both fish
      and prey biomass declined, such that the ratio of fish to prey remained
      unchanged. Consequently, even at frequently trawled sites with low prey biomass,
      both plaice and dab maintained constant levels of stomach fullness and gut energy
      contents. However, dietary shifts in plaice towards energy-poor prey items were
      evident when prey species were analysed individually. This, together with a
      potential decrease in foraging efficiency due to low prey densities, was seen as
      the most plausible cause for the reduced body condition observed. Understanding
      the relationship between trawling, benthic impacts, fish foraging and resultant
      body condition is an important step in designing successful mitigation measures
      for future management strategies in bottom trawl fisheries.

PMID- 25621337
TI  - Background level of risk and the survival of predator-naive prey: can neophobia
      compensate for predator naivety in juvenile coral reef fishes?
AB  - Neophobia--the generalized fear response to novel stimuli--provides the first
      potential strategy that predator-naive prey may use to survive initial predator
      encounters. This phenotype appears to be highly plastic and present in
      individuals experiencing high-risk environments, but rarer in those experiencing
      low-risk environments. Despite the appeal of this strategy as a 'solution' for
      prey naivety, we lack evidence that this strategy provides any fitness benefit to
      prey. Here, we compare the relative effect of environmental risk (high versus
      low) and predator-recognition training (predator-naive versus predator
      experienced individuals) on the survival of juvenile fish in the wild. We found
      that juveniles raised in high-risk conditions survived better than those raised
      in low-risk conditions, providing the first empirical evidence that environmental
      risk, in the absence of any predator-specific information, affects the way naive
      prey survive in a novel environment. Both risk level and experience affected
      survival; however, the two factors did not interact, indicating that the
      information provided by both factors did not interfere or enhance each other.
      From a mechanistic viewpoint, this indicates that the combination of the two
      factors may increase the intensity, and hence efficacy, of prey evasion
      strategies, or that both factors provide qualitatively separate benefits that
      would result in an additive survival success.

PMID- 25621338
TI  - Images of the month. Achalasia with an elbow.

PMID- 25621339
TI  - Alexandre Afranio Peixoto (1963-2013).

PMID- 25621340
TI  - Two large RCTs fail to demonstrate any  benefit of bisphosphonates in breast 
      cancer.

PMID- 25621341
TI  - Hormone therapy in early menopause  does not slow progression of 
      atherosclerosis.

PMID- 25621342
TI  - More guidelines for the care of midlife  women.

PMID- 25621343
TI  - AMH in the prediction of age at  menopause.

PMID- 25621344
TI  - Reply: To PMID 23921359.

PMID- 25621345
TI  - CT screening for lung cancer shown to be cost-effective.

PMID- 25621346
TI  - Poor housing quality linked to asthma flare ups.

PMID- 25621347
TI  - Canberra Government to demolish asbestos-contaminated  homes.

PMID- 25621348
TI  - Adenotonsillectomy improves asthma outcomes in children.

PMID- 25621349
TI  - Designing out the risk of infection in cystic fibrosis.

PMID- 25621350
TI  - Charting a new future.

PMID- 25621352
TI  - The Institute of Circulatory and Respiratory Health strategic plan for 2013-2016
      executive summary.

PMID- 25621351
TI  - Prevalence of atrial fibrillation in patients with high CHADS2- and CHA2DS2VASc
      scores: anticoagulate or monitor high-risk patients?
AB  - BACKGROUND: In patients with known atrial fibrillation (AF) different scores are
      utilized to estimate the risk of thromboembolic events and guide oral
      anticoagulation. Diagnosis of AF strongly depends on the duration of
      electrocardiogram monitoring. The aim of this study was to use established scores
      to predict the prevalence of AF. METHODS: The CHADS2- (Congestive Heart failure,
      hypertension, Age >75 years, Diabetes, Stroke [doubled]) and CHA2DS2VASc-score
      (Congestive Heart failure, hypertension, Age >=75 years [doubled], Diabetes,
      Stroke [doubled], Vascular disease, Age 65-74 years, Sex category [female sex])
      was calculated in 150,408 consecutive patients, referred to the University
      Hospital of Rostock between 2007 and 2012. All factors constituting these scores
      and a history of AF were prospectively documented with the ICD-10 admission
      codes. RESULTS: Mean age of our study population was 67.6 +/- 13.6 years with a
      mean CHADS2-score of 1.65 +/- 0.92 and CHA2DS2VASc-score of 3.04 +/- 1.42. AF was
      prevalent in 15.9% of the participants. The prevalence of AF increased
      significantly with every CHADS2- and CHA2DS2VASc-score point up to 54.2% in
      CHADS2-score of 6 and 71.4% in CHA2DS2VASc-score of 9 (P < 0.001). CONCLUSION:
      The prevalence of AF increases with increasing CHADS2- and CHA2DS2VASc-score. In
      intermediate scores intensified monitoring may be recommended. In high scores,
      thromboembolic complications occurred irrespective of the presence of AF and
      anticoagulant therapy may be initiated irrespective of documented AF.

PMID- 25621353
TI  - Strength through leadership, knowledge and community.

PMID- 25621354
TI  - Trans-Atlantic debate: Whether evidence supports reducing the threshold diameter
      to 5 cm for elective interventions in women with abdominal aortic aneurysms.

PMID- 25621355
TI  - Trans-Atlantic debate: Does evidence support reducing the threshold diameter to 5
      cm for elective interventions in women with abdominal aortic aneurysms?

PMID- 25621356
TI  - February is American Heart Month.

PMID- 25621357
TI  - Reducing cardiovascular disease risk with exercise.

PMID- 25621358
TI  - Archival bone marrow samples: suitable for multiple biomarker analysis.
AB  - AB Archival samples represent a significant potential for genetic studies,
      particularly in severe diseases with risk of lethal outcome, such as in cancer.
      In this pilot study, we aimed to evaluate the usability of archival bone marrow
      smears and biopsies for DNA extraction and purification, whole genome
      amplification (WGA), multiple marker analysis including 10 short tandem repeats,
      and finally a comprehensive genotyping of 33,683 single nucleotide polymorphisms
      (SNPs) with multiplexed targeted next-generation sequencing. A total of 73
      samples from 21 bone marrow smears and 13 bone marrow biopsies from 18 Danish and
      Norwegian childhood acute lymphoblastic leukemia patients were included and
      compared with corresponding blood samples. Samples were grouped according to the
      age of sample and whether WGA was performed or not. We found that measurements of
      DNA concentration after DNA extraction was dependent on detection method and that
      spectrophotometry overestimated DNA amount compared with fluorometry. In the
      short tandem repeat analysis, detection rate dropped slightly with longer
      fragments. After WGA, this drop was more pronounced. Samples stored for 0 to 3
      years showed better results compared with samples stored for 4 to 10 years.
      Acceptable call rates for SNPs were detected for 7 of 42 archival samples. In
      conclusion, archival bone marrow samples are suitable for DNA extraction and
      multiple marker analysis, but WGA was less successful, especially when longer
      fragments were analyzed. Multiple SNP analysis seems feasible, but the method has
      to be further optimized.

PMID- 25621359
TI  - Curious beads for a clinical pearl.

PMID- 25621360
TI  - Whole genome response in guinea pigs infected with the high virulence strain
      Mycobacterium tuberculosis TT372.
AB  - In this study we conducted a microarray-based whole genomic analysis of gene
      expression in the lungs after exposure of guinea pigs to a low dose aerosol of
      the Atypical Beijing Western Cape TT372 strain of Mycobacterium tuberculosis,
      after harvesting lung tissues three weeks after infection at a time that effector
      immunity is starting to peak. The infection resulted in a very large up
      regulation of multiple genes at this time, particularly in the context of a
      "chemokine storm" in the lungs. Overall gene expression was considerably reduced
      in animals that had been vaccinated with BCG two months earlier, but in both
      cases strong signatures featuring gamma interferon [IFNgamma] and tumor necrosis
      factor [TNFalpha] were observed indicating the potent TH1 response in these
      animals. Even though their effects are not seen until later in the infection,
      even at this early time point gene expression patterns associated with the
      potential emergence of regulatory T cells were observed. Genes involving lung
      repair, response to oxidative stress, and cell trafficking were strongly
      expressed, but interesting these gene patterns differed substantially between the
      infected and vaccinated/infected groups of animals. Given the importance of this
      species as a relevant and cost-effective small animal model of tuberculosis, this
      approach has the potential to provide new information regarding the effects of
      vaccination on control of the disease process.

PMID- 25621362
TI  - Chest X-ray quiz.

PMID- 25621361
TI  - Enhancement of in vitro activity of tuberculosis drugs by addition of
      thioridazine is not reflected by improved in vivo therapeutic efficacy.
AB  - OBJECTIVES: Assessment of the activity of thioridazine towards Mycobacterium
      tuberculosis (Mtb), in vitro and in vivo as a single drug and in combination with
      tuberculosis (TB) drugs. METHODS: The in vitro activity of thioridazine as single
      drug or in combination with TB drugs was assessed in terms of MIC and by use of
      the time-kill kinetics assay. Various Mtb strains among which the Beijing
      genotype strain BE-1585 were included. In vivo, mice with TB induced by BE-1585
      were treated with a TB drug regimen with thioridazine during 13 weeks.
      Therapeutic efficacy was assessed by the change in mycobacterial load in the
      lung, spleen and liver during treatment and 13 weeks post-treatment. RESULTS: In
      vitro, thioridazine showed a concentration-dependent and time-dependent
      bactericidal activity towards both actively-replicating and slowly-replicating
      Mtb. Thioridazine at high concentrations could enhance the activity of isoniazid
      and rifampicin, and in case of isoniazid resulted in elimination of mycobacteria
      and prevention of isoniazid-resistant mutants. Thioridazine had no added value in
      combination with moxifloxacin or amikacin. In mice with TB, thioridazine was
      poorly tolerated, limiting the maximum tolerated dose (MTD). The addition of
      thioridazine at the MTD to an isoniazid-rifampicin-pyrazinamide regimen for 13
      weeks did not result in enhanced therapeutic efficacy. CONCLUSIONS: Thioridazine
      is bactericidal towards Mtb in vitro, irrespective the mycobacterial growth rate
      and results in enhanced activity of the standard regimen. The in vitro activity
      of thioridazine in potentiating isoniazid and rifampicin is not reflected by
      improved therapeutic efficacy in a murine TB-model.

PMID- 25621363
TI  - [A rare ciliopathy: the Bardet-Biedl Syndrome].

PMID- 25621364
TI  - [Joint Statement of the German Society of Gastroenterology, Digestive and
      Metabolic Diseases (DGVS) and the German Society for Internal Medicine (DGIM) to
      Simeprevir-benefit assessment according to S 35a SGB V the Federal Joint
      Committee].

PMID- 25621365
TI  - Response.

PMID- 25621366
TI  - Telesonography - the 5th dimension of  ultrasound examination.

PMID- 25621367
TI  - Trust and scientific publication: AJB policy for digital images.

PMID- 25621368
TI  - Empowering a diverse community.

PMID- 25621369
TI  - Understanding chronic pain.

PMID- 25621370
TI  - Advocating for those with disabilities.

PMID- 25621371
TI  - Modulating the activity of protein conjugated to gold nanoparticles by site
      directed orientation and surface density of bound protein.
AB  - The key property of protein-nanoparticle conjugates is the bioactivity of the
      protein. The ability to accurately modulate the activity of protein on the
      nanoparticles at the interfaces is important in many applications. In the work
      reported here, modulation of the activity of protein-gold nanoparticle (AuNP)
      conjugates by specifically orienting the protein and by varying the surface
      density of the protein was investigated. Different orientations were achieved by
      introducing cysteine (Cys) residues at specific sites for binding to gold. We
      chose Escherichia coli inorganic pyrophosphatase (PPase) as a model protein and
      used site-directed mutagenesis to generate two mutant types (MTs) with a single
      Cys residue on the surface: MT1 with Cys near the active center and MT2 with Cys
      far from the active center. The relative activities of AuNP conjugates with wild
      type (WT), MT1, and MT2 were found to be 44.8%, 68.8%, and 91.2% of native PPase
      in aqueous solution. Site-directed orientation with the binding site far from the
      active center thus allowed almost complete preservation of the protein activity.
      The relative activity of WT and MT2 conjugates did not change with the surface
      density of the protein, while that of MT1 increased significantly with increasing
      surface density. These results demonstrate that site-directed orientation and
      surface density can both modulate the activity of proteins conjugated to AuNP and
      that orientation has a greater effect than density. Furthermore, increasing the
      surface density of the specifically oriented protein MT2, while having no
      significant effect on the specific activity of the protein, still allowed
      increased protein loading on the AuNP and thus increased the total protein
      activity. This is of great importance in the study on the interface of protein
      and nanoparticle and the applications for enzyme immobilization, drug delivery,
      and biocatalysis. 

PMID- 25621372
TI  - Nanoscale topography influences polymer surface diffusion.
AB  - Using high-throughput single-molecule tracking, we studied the diffusion of
      poly(ethylene glycol) chains at the interface between water and a hydrophobic
      surface patterned with an array of hexagonally arranged nanopillars. Polymer
      molecules displayed anomalous diffusion; in particular, they exhibited
      intermittent motion (i.e., immobilization and "hopping") suggestive of continuous
      time random walk (CTRW) behavior associated with desorption-mediated surface
      diffusion. The statistics of the molecular trajectories changed systematically on
      surfaces with pillars of increasing height, exhibiting motion that was
      increasingly subdiffusive and with longer waiting times between diffusive steps.
      The trajectories were well-described by kinetic Monte Carlo simulations of CTRW
      motion in the presence of randomly distributed permeable obstacles, where the
      permeability (the main undetermined parameter) was conceptually related to the
      obstacle height. These findings provide new insights into the mechanisms of
      interfacial transport in the presence of obstacles and on nanotopographically
      patterned surfaces. 

PMID- 25621373
TI  - Specific protein detection using designed DNA carriers and nanopores.
AB  - Nanopores are a versatile technique for the detection and characterization of
      single molecules in solution. An ongoing challenge in the field is to find
      methods to selectively detect specific biomolecules. In this work we describe a
      new technique for sensing specific proteins using unmodified solid-state
      nanopores. We engineered a double strand of DNA by hybridizing nearly two hundred
      oligonucleotides to a linearized version of the m13mp18 virus genome. This
      engineered double strand, which we call a DNA carrier, allows positioning of
      protein binding sites at nanometer accurate intervals along its contour via DNA
      conjugation chemistry. We measure the ionic current signal of translocating DNA
      carriers as a function of the number of binding sites and show detection down to
      the single protein level. Furthermore, we use DNA carriers to develop an assay
      for identifying a single protein species within a protein mixture. 

PMID- 25621374
TI  - TGF-beta2 is involved in the preservation of the chondrocyte phenotype under
      hypoxic conditions.
AB  - Culturing chondrocytes under oxygen tension closely resembling their in vivo
      environment has been shown to have positive effects on matrix synthesis. In
      redifferentiation of expanded chondrocytes, hypoxia increased collagen type II
      expression. However, the mechanism by which hypoxia enhances redifferentiation is
      still unknown. We employed novel bioreactor technology to investigate the role of
      TGF-beta, a growth factor heavily implicated in matrix production, in
      chondrocytes under hypoxia. Dedifferentiated chondrocytes in alginate were
      cultured for 48h under hypoxic (1% pO2) or normoxic (20%) conditions, using
      specialized bioreactor technology. Hypoxia induced gene expression (GDF1-, PHD3,
      HAS2, VEGF, COX2), chondrocyte markers (SOX9, COL2, COL1, AGC1 and MMP13), as
      well as components of the TGF-beta signaling pathway (TGF-beta isoforms,
      receptors, and downstream effectors) were analyzed by qPCR after 48h. In
      addition, protein expression of COL2 and TGF-beta2 were evaluated. To further
      elucidate the involvement of the TGF-beta2, we used siRNA and ALK5 inhibition.
      Hypoxic culture showed robust upregulation of hypoxic markers as well as
      upregulation of SOX9 and COL2 expression. Of all TGF-beta isoforms, only TGF
      beta2 was upregulated under hypoxia on both gene and protein level. In addition,
      both type I receptors (ALK1 and ALK5) were upregulated under hypoxia, but type II
      and III receptors were not. TGF-beta2 downregulation via siRNA abrogated the
      hypoxia-induced COL2 expression, as did ALK5 inhibition, giving a strong
      indication that this pathway is involved in chondrocyte redifferentiation under
      low oxygen tension. Hypoxic culture is a common approach for cartilage tissue
      engineering, but its underlying mechanisms are still poorly understood. Here, we
      show that increased TGF-beta2 signaling through ALK5 plays a role in hypoxia
      induced redifferentiation of chondrocytes. 

PMID- 25621375
TI  - Biomimetic total synthesis of gracilioethers B and C.
AB  - Total syntheses of the marine polyketide metabolites gracilioethers B and C have
      been realized in 9 steps (40% overall yield) and 10 steps (34% overall yield),
      respectively. The [2(5H)-furanylidene]ethanoate (furanylidene) motif was
      constructed in a transacetalization/dehydration cascade of an advanced beta
      ketoester intermediate, which was designed to mimic a postulated biosynthetic
      precursor to the natural products. The relative and absolute configurations of
      gracilioethers B and C are confirmed as (6R,8R) and (6R,8R,11S), respectively. 

PMID- 25621376
TI  - The conjunction fallacy, confirmation, and quantum theory: comment on Tentori,
      Crupi, and Russo (2013).
AB  - The conjunction fallacy refers to situations when a person judges a conjunction
      to be more likely than one of the individual conjuncts, which is a violation of a
      key property of classical probability theory. Recently, quantum probability (QP)
      theory has been proposed as a coherent account of these and many other findings
      on probability judgment "errors" that violate classical probability rules,
      including the conjunction fallacy. Tentori, Crupi, and Russo (2013) presented an
      alternative account of the conjunction fallacy based on the concept of inductive
      confirmation. They presented new empirical findings consistent with their
      account, and they also claimed that these results were inconsistent with the QP
      theory account. This comment proved that our QP model for the conjunction fallacy
      is completely consistent with the main empirical results from Tentori et al.
      (2013). Furthermore, we discuss experimental tests that can distinguish the 2
      alternative accounts.

PMID- 25621377
TI  - Automaticity of unconscious response inhibition: comment on Chiu and Aron (2014).
AB  - A recent study (Chiu & Aron, 2014) suggested that unconscious response inhibition
      is maintained when subliminal stimuli are mixed with supraliminal stimuli that
      are associated with response inhibition (mixed session), but it is abolished when
      they are presented alone (single session). However, awareness of the subliminal
      stimuli is likely to differ in the 2 sessions because of priming of awareness-
      awareness for subliminal stimuli is elevated (e.g., no longer subliminal) when
      mixed with supraliminal stimuli (Lin & Murray, 2014a). Here, in a novel design,
      we measured the awareness level in both sessions and found that the session
      dependent effect was due to an awareness difference: The effect disappeared when
      awareness was comparable and emerged only when awareness was different. Arguments
      based on the lack of correlation between awareness and unconscious effects are
      refuted because typical correlation analysis underestimates the true correlation
      because of range restriction and it speaks only about individual differences that
      cannot explain within-subject effects (e.g., stimulus context here). Our findings
      also point to an attention-based mechanism underlying priming of awareness:
      Supraliminal trials are less attention-demanding, allowing for more attentional
      resources for subliminal trials in the mixed than single sessions. We discuss 2
      implications. First, unconscious effects depend on top-down task sets and bottom
      up stimulus strength. Second, to properly demonstrate unconscious processing, we
      stress the importance of having equivalent trial sequences between the main and
      awareness tests, promote a conjunction method that can strengthen inference, and
      discuss establishing a limit for equivalence between observed and chance
      performance.

PMID- 25621378
TI  - The effect of horizontal eye movements on free recall: a preregistered
      adversarial collaboration.
AB  - A growing body of research has suggested that horizontal saccadic eye movements
      facilitate the retrieval of episodic memories in free recall and recognition
      memory tasks. Nevertheless, a minority of studies have failed to replicate this
      effect. This article attempts to resolve the inconsistent results by introducing
      a novel variant of proponent-skeptic collaboration. The proposed approach
      combines the features of adversarial collaboration and purely confirmatory
      preregistered research. Prior to data collection, the adversaries reached
      consensus on an optimal research design, formulated their expectations, and
      agreed to submit the findings to an academic journal regardless of the outcome.
      To increase transparency and secure the purely confirmatory nature of the
      investigation, the 2 parties set up a publicly available adversarial
      collaboration agreement that detailed the proposed design and all foreseeable
      aspects of the data analysis. As anticipated by the skeptics, a series of
      Bayesian hypothesis tests indicated that horizontal eye movements did not improve
      free recall performance. The skeptics suggested that the nonreplication may
      partly reflect the use of suboptimal and questionable research practices in
      earlier eye movement studies. The proponents countered this suggestion and used a
      p curve analysis to argue that the effect of horizontal eye movements on explicit
      memory did not merely reflect selective reporting.

PMID- 25621379
TI  - Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil  Cyanobacterium
      Desmonostoc muscorum, Permeabilizes  Phospholipid Membranes by Reducing Their
      Fluidity.
AB  - There is mounting evidence that cyanobacterial lipopeptides can kill mammalian
      cells, presenting a hazard to human health. Unfortunately, their mechanism of
      toxicity is poorly understood. We have isolated new cyclic undecalipopeptides
      muscotoxin A and B containing unique lipophilicresidue 3-amino-2,5
      dihydroxydecanoic acid (5-OH Ahdoa). Muscotoxin B was not used for biological
      studies due to its poor yield. Muscotoxin A was cytotoxic to YAC-1, Sp/2, and
      HeLa cancer cell lines (LC(50) ranged from 9.9 to 13.2 MUM after 24 h of
      exposure), causing membrane damage and influx of calcium ions. Subsequently, we
      studied this lytic mechanism using synthetic liposomes with encapsulated
      fluorescent probes. Muscotoxin A permeabilized liposomes composed exclusively of
      phospholipids, demonstrating that no proteins or carbohydrates present in
      biomembranes are essential for its activity. Paradoxically, the permeabilization
      activity of muscotoxin A was mediated by a significant reduction in membrane
      surface fluidity (stiffening), the opposite of that caused by synthetic
      detergents and cytolytic lipopeptide puwainaphycin F. At 25  degrees C,
      muscotoxin A disrupted liposomes with and without cholesterol/sphingomyelin;
      however, at 37  degrees C, it was selective against liposomes with
      cholesterol/sphingomyelin. It appears that both membrane fluidity and
      organization can affect the lytic activity of muscotoxin A. Our findings
      strengthen the evidence that cyanobacterial lipopeptides specifically disrupt
      mammalian cell membranes and bring new insights into the mechanism of this
      effect.

PMID- 25621380
TI  - Compound-specific carbon, nitrogen, and hydrogen isotope analysis of N
      nitrosodimethylamine in aqueous solutions.
AB  - Mitigation of N-nitrosodimethylamine (NDMA) and other hazardous water
      disinfection byproducts (DBP) is currently hampered by a limited understanding of
      DBP formation mechanisms. Because variations of the stable isotope composition of
      NDMA can potentially reveal reaction pathways and precursor compounds, we
      developed a method for the compound-specific isotope analysis (CSIA) of
      (13)C/(12)C, (15)N/(14)N, and (2)H/(1)H ratios of NDMA by gas chromatography
      coupled to isotope ratio mass spectrometry (GC/IRMS). Method quantification
      limits for the accurate isotope analysis of NDMA, N-nitrosodiethyl-, -dipropyl-,
      and -dibutylamine as well as N-nitrosopyrrolidine were between 0.18 to 0.60 nmol
      C, 0.40 to 0.80 nmol N, and 2.2 to 5.8 nmol H injected on column. Coupling solid
      phase extraction (SPE) to GC/IRMS enabled the precise quantification of C, N, and
      H isotope ratios of NDMA in aqueous samples at concentrations of 0.6 MUM (45 MUg
      L(-1)). We validated the proposed method with a laboratory experiment, in which
      NDMA was formed with stoichiometric yield (97 +/- 4%) through chloramination of
      the pharmaceutical ranitidine (3 MUM). delta(13)C and delta(2)H values of NDMA
      remained constant during NDMA formation while its delta(15)N increased due to a
      reaction at a N atom in the rate-limiting step of NDMA formation. The delta(2)H
      value of NDMA determined by SPE-GC/IRMS also corresponded well to the delta(2)H
      value of the N(CH3)2-group of ranitidine measured by quantitative deuterium
      nuclear magnetic resonance spectroscopy. This observation implies that the
      N(CH3)2-moiety of ranitidine is transferred to NDMA without being chemically
      altered and illustrates the accuracy of the proposed method. 

PMID- 25621381
TI  - Correction to "direct catalytic N-alkylation of amines with carboxylic acids".

PMID- 25621382
TI  - Staghorn Sumac Reduces 5-Fluorouracil-Induced Toxicity in Normal Cells.
AB  - Edible staghorn sumac (Rhus hirta) fruit extract was applied in conjunction with
      chemotherapeutic drug 5-fluorouracil to promote cytotoxicity of the drugs toward
      human breast cancer cells MCF-7 while protecting normal cells MCF-10A from drug
      toxicity. Sumac extract would be a promising chemotherapeutic drug conjugate in
      cancer chemotherapy. 

PMID- 25621383
TI  - Multidrug-resistant pathogens in the food supply.
AB  - Antimicrobial resistance, including multidrug resistance (MDR), is an increasing
      problem globally. MDR bacteria are frequently detected in humans and animals from
      both more- and less-developed countries and pose a serious concern for human
      health. Infections caused by MDR microbes may increase morbidity and mortality
      and require use of expensive drugs and prolonged hospitalization. Humans may be
      exposed to MDR pathogens through exposure to environments at health-care
      facilities and farms, livestock and companion animals, human food, and exposure
      to other individuals carrying MDR microbes. The Centers for Disease Control and
      Prevention classifies drug-resistant foodborne bacteria, including Campylobacter,
      Salmonella Typhi, nontyphoidal salmonellae, and Shigella, as serious threats. MDR
      bacteria have been detected in both meat and fresh produce. Salmonellae carrying
      genes coding for resistance to multiple antibiotics have caused numerous
      foodborne MDR outbreaks. While there is some level of resistance to
      antimicrobials in environmental bacteria, the widespread use of antibiotics in
      medicine and agriculture has driven the selection of a great variety of microbes
      with resistance to multiple antimicrobials. MDR bacteria on meat may have
      originated in veterinary health-care settings or on farms where animals are given
      antibiotics in feed or to treat infections. Fresh produce may be contaminated by
      irrigation or wash water containing MDR bacteria. Livestock, fruits, and
      vegetables may also be contaminated by food handlers, farmers, and animal
      caretakers who carry MDR bacteria. All potential sources of MDR bacteria should
      be considered and strategies devised to reduce their presence in foods.
      Surveillance studies have documented increasing trends in MDR in many pathogens,
      although there are a few reports of the decline of certain multidrug pathogens.
      Better coordination of surveillance programs and strategies for controlling use
      of antimicrobials need to be implemented in both human and animal medicine and
      agriculture and in countries around the world.

PMID- 25621384
TI  - Group Balance Training Specifically Designed for Individuals With Alzheimer
      Disease: Impact on Berg Balance Scale, Timed Up and Go, Gait Speed, and Mini
      Mental Status Examination.
AB  - BACKGROUND AND PURPOSE: Individuals with Alzheimer disease (IwAD) experience more
      frequent and more injurious falls than their cognitively intact peers. Evidence
      of balance and gait dysfunction is observed earlier in the course of Alzheimer
      disease (AD) than once believed. Balance training has been demonstrated to be
      effective in improving balance and decreasing falls in cognitively intact older
      adults but is not well studied in IwAD. This study was designed to analyze the
      effects of a group balance training program on balance and falls in IwAD. The
      program was developed specifically for IwAD, with explicit guidelines for
      communication/interaction and deliberate structure of training sessions catered
      to the motor learning needs of IwAD. DESIGN: This prospective, quasi
      experimental, pretest-posttest design study describes the effects of a balance
      training program for a cohort of IwAD. METHODS: Thirty IwAD were recruited from 3
      adult day health centers; 22 completed at least 1 posttest session. Participants
      were tested with Berg Balance Scale (BBS), Timed Up and Go (TUG), Self-Selected
      Gait Speed (SSGS), Fast Gait Speed (FGS), and Mini-Mental Status Examination
      (MMSE) immediately before and after the 3-month intervention and again 3 months
      later. Group training was held at the adult day health centers for 45 minutes,
      twice per week. Sessions were characterized by massed, constant, and blocked
      practice of functional, relevant activities with considerable repetition. Ratio
      of participant to staff member never exceeded 3:1. Physical therapist staff
      members assured that participants were up on their feet the majority of each
      session and were individually challenged as much as possible. RESULTS: Repeated
      measures analysis of variance (ANOVA) for BBS was significant (F = 15.04; df =
      1.67/28.40; P = .000) with post hoc tests, revealing improvement between pretest
      and immediate posttest (P = .000) and decline in performance between immediate
      and 3-month posttest (P = .012). Repeated-measures ANOVA posttest for MMSE was
      significant (F = 5.12; df = 1.73/22.53; P = .018) with post hoc tests, showing no
      change in MMSE between pretest and immediate posttest but decline in MMSE when
      comparing immediate posttest with 3-month posttest (P = .038) and pretest with 3
      month posttest (P = .019). Repeated-measures ANOVA for TUG, FGS, and SSGS were
      not significant. Immediate effects of the intervention as assessed by the a
      priori paired t tests (comparing pre- and immediate posttest data) revealed
      significant improvement in BBS (t = -7.010; df = 20; P = .000), TUG (t = 3.103;
      df = 20; P = .006), and FGS (t = -2.115; df = 19; P = .048), but not in SSGS (t =
      -1.456; df = 20; P = .161). DISCUSSION AND CONCLUSION: The 3-month group balance
      training intervention designed specifically for IwAD was effective in improving
      balance and mobility, as evidenced by improved BBS and TUG performances.
      Cognition did not decline during the course of the intervention but did decline
      following the intervention, suggesting a possible protective effect. Given the
      promising findings, a larger-scale controlled study is warranted.

PMID- 25621385
TI  - The Coach2Move Approach: Development and Acceptability of an Individually
      Tailored Physical Therapy Strategy to Increase Activity Levels in Older Adults
      With Mobility Problems.
AB  - BACKGROUND AND PURPOSE: Despite the positive effects of physical activity on
      numerous aspects of health, many older adults remain sedentary even after
      participating in physical activity interventions. Standardized exercise programs
      do not necessarily bring about the behavioral change that is necessary.
      Therefore, a patient-centered approach is needed. The purpose of this study was
      to develop and assess the acceptability and potential effectiveness of the
      Coach2Move strategy; a physical therapy (PT) approach aimed at improving the long
      term level of physical activity in mobility-limited older adults. METHODS: The
      Coach2Move strategy was developed on the basis of 2 systematic literature studies
      and expert consultations. Multiple focus group meetings and a Delphi procedure
      were organized to gain consensus on the Coach2Move strategy. Acceptability and
      potential effectiveness were studied in a pilot study with a pre-/postdesign in
      which 2 physical therapists and 12 patients participated. To assess
      acceptability, patients were interviewed, discussion were held with the involved
      physical therapists was held, and health records were studied. Potential
      effectiveness was tested measuring the level of physical activity, frailty,
      quality of life, and mobility before and after treatment. RESULTS: On the basis
      of the literature study and expert consultations, an algorithm based on the
      Hypothesis Oriented Algorithm for Clinicians Part II was developed: the
      Coach2Move approach. Key elements of the Coach2Move approach include an extensive
      intake using motivational interviewing, clinical reasoning, coaching to increase
      physical activity and self-management, focusing on meaningful activities, and
      working according to 3 patient-tailored intervention profiles with a predefined
      number of sessions. The pilot study showed high appraisal of the strategy by both
      physical therapists and patients. Moreover, a potential effect on the level of
      physical activity, frailty, quality of life, and mobility was observed.
      DISCUSSION AND CONCLUSION: Because the pilot study was not randomized or
      controlled and included a small sample, no conclusions can be drawn about the
      effectiveness of the Coach2Move strategy. However, all suggestions made in this
      study were implemented in an ongoing, randomized controlled trial in which the
      Coach2Move strategy will be compared to usual care PT. In conclusion, the
      Coach2Move strategy can be considered acceptable in PT practice and showed
      potential benefits. The results on the (cost-)effectiveness of this strategy
      based on a large, randomized, controlled trial are expected in 2014.

PMID- 25621386
TI  - One-pot synthesis of imines from nitroaromatics and alcohols by tandem
      photocatalytic and catalytic reactions on Degussa (Evonik) P25 titanium dioxide.
AB  - Photoirradiation (lambda > 300 nm) of Degussa (Evonik) P25 TiO2, a mixture of
      anatase and rutile particles, in alcohols containing nitroaromatics at room
      temperature produces the corresponding imines with very high yields (80-96%).
      Other commercially available anatase or rutile TiO2 particles, however, exhibit
      very low yields (<30%). The imine formation involves two step reactions on the
      TiO2 surface: (i) photocatalytic oxidation of alcohols (aldehyde formation) and
      reduction of nitrobenzene (aniline formation) and (ii) condensation of the formed
      aldehyde and aniline on the Lewis acid sites (imine formation). The respective
      anatase and rutile particles were isolated from P25 TiO2 by the H2O2/NH3 and HF
      treatments to clarify the activity of these two step reactions. Photocatalysis
      experiments revealed that the active sites for photocatalytic reactions on P25
      TiO2 are the rutile particles, promoting efficient reduction of nitrobenzene on
      the surface defects. In contrast, catalysis experiments showed that the anatase
      particles isolated from P25 TiO2 exhibit very high activity for condensation of
      aldehyde and aniline, because the number of Lewis acid sites on the particles (73
      MUmol g(-1)) is much higher than that of other commercially available anatase or
      rutile particles (<15 MUmol g(-1)). The P25 TiO2 particles therefore successfully
      promote tandem photocatalytic and catalytic reactions on the respective rutile
      and anatase particles, thus producing imines with very high yields. 

PMID- 25621387
TI  - Fluoride removal from groundwater by limestone treatment in presence of
      phosphoric acid.
AB  - Fluoride removal from groundwater has been studied by addition of dilute
      phosphoric acid (PA) to the influent water before limestone treatment through
      laboratory plug-flow column experiments and bench-scale plug-flow pilot tests. In
      this PA-enhanced limestone defluoridation (PAELD) technique, fluoride is removed
      from 0.526 mM to 0.50-52.60 MUM in 3 h with near neutral final pH. The presence
      of PA increases the fluoride removal capacity of limestone to 1.10 mg/g compared
      to 0.39 mg/g reported in its absence. The changes in fluoride removal with
      variation in initial PA concentration, initial fluoride concentration and the
      final pH have been found to be statistically significant with p < 0.05. The
      estimated recurring cost is US$ ~0.58/m(3) water. Simple scrubbing and rinsing is
      a preferable method for regeneration of limestone as it is almost equally
      effective with lime or NaOH. Sorption of fluoride by calcium phosphates produced
      in situ in the reactor is the dominant mechanism of fluoride removal in the
      PAELD. Precipitation of CaF2 and sorption of fluoride by the limestone also
      contribute to the fluoride removal. High efficiency, capacity, safety,
      environment-friendliness, low cost and simplicity of operation make the PAELD a
      potential technique for rural application. 

PMID- 25621388
TI  - Nitrogen enrichment potential of biochar in relation to pyrolysis temperature and
      feedstock quality.
AB  - Nitrogen (N) enrichment of biochar from both inorganic and organic waste N
      sources has the potential to add economic and environmental value through its use
      as a slow release N fertilizer. We investigated the sorption of N by, and its
      release from, biochar made at pyrolysis temperatures of 400, 500 and 600  degrees
      C from three feedstocks: poultry litter (PL with a carbon (C) to N ratio (C:N) of
      14), softwood chips of spruce-pine-fir (SPF with a C:N of 470), and a 50:50
      mixture of PL and SPF (PL/SPF). The prepared biochars were enriched with ammonium
      nitrate (AN) and urea ammonium nitrate (UAN). PL biochars had the lowest C
      content (50-56% C), but the highest pH (9.3-9.9), electrical conductivity (EC,
      780-960 dS m(-1)), cation exchange capacity (CEC, 40-46 cmol kg(-1)), and N
      content (3.3-4.5%). While N content and hydrogen (H) to C atomic ratio (H:C)
      decreased with increasing pyrolysis temperature irrespective of the feedstock
      used, both pH and EC slightly increased with pyrolysis temperature for all
      feedstocks. The PL and SPF biochars showed similar H:C and also similar N
      sorption and N release at all pyrolysis temperatures. These biochars sorbed up to
      5% N by mass, irrespective of the source of N. However, PL/SPF biochar performed
      poorly in sorbing N from either AN or UAN. Biochar H:C was found to be unrelated
      to N sorption rates, suggesting that physical adsorption on active surfaces was
      the main mechanism of N sorption in these biochars. There were minor differences
      between N sorbed from NO3-N and NH4-N among different biochars. Very small
      amounts of sorbed N (0.2-0.4 mg N g(-1) biochar) was released when extracted with
      1 M KCl solution, indicating that the retained N was strongly held in complex
      bonds, more so for NH4-N because the release of NO3-N was 3-4 times greater than
      that of NH4-N. NH4-N sorption far exceeded the effective CEC of the biochars,
      thereby suggesting that most of the sorption may be due to physical entrapment of
      NH4(+) in biochar pores. The results of this study suggest that biochar can be
      used to remove excess N from poultry and dairy manure and be a good mitigation
      option for reducing N leaching and gaseous losses. 

PMID- 25621389
TI  - Combining direct and indirect impacts to assess ecosystem service loss due to
      infrastructure construction.
AB  - The destruction of natural habitats and the associated loss of Ecosystem Services
      (ES) are rarely jointly assessed and quantified in Environmental Impact
      Assessment (EIA). Based on a terrestrial transport infrastructure project, the
      objective of this paper is to quantify the potential loss of ES associated with
      direct and indirect impacts, and illustrate their contribution to decision-making
      for route options. We first quantify how much of each type of ES is generated by
      different land units in the absence of the infrastructure (baseline conditions).
      We then estimate ES loss caused by infrastructure construction in a way that
      discriminates among different types of ES and losses because some ES, in addition
      to losses that are directly proportional to the surface impacted, can show
      additional indirect losses associated with landscape connectivity. In addition,
      we illustrate how the assessment of threshold effects in particular ecosystem
      types that may be most sensitive to their occurrence can affect the estimation of
      ES loss. We compare implementation options to provide an example of how choices
      can be improved by assessing ES loss associated with a combination of direct and
      indirect impacts. This kind of analysis could be used more generally to assess
      development projects simply by adapting the framework of analysis to the type of
      project and the ecosystems concerned. 

PMID- 25621390
TI  - Clinical considerations for the development of biosimilars in oncology.
AB  - Despite availability of biologic therapies, limited patient access to many of the
      most-effective cancer treatments affects overall health outcomes. To address this
      issue, many governments have enacted legislation for the approval of biosimilars.
      The term "biosimilar" refers to a biologic product that is developed to be highly
      similar, as opposed to identical, to a licensed biologic product (the reference
      or innovator product), such that, per US Food and Drug administration draft
      guidelines, "no clinically meaningful differences [exist] between the biological
      product and the reference product in terms of safety, purity, and potency." This
      article presents some considerations about the development of biosimilars in
      cancer treatment through an overview of biosimilars from a clinical perspective.
      Topics covered include the development requirements and unique regulatory
      requirements for biosimilars, labeling considerations, potential limitations to
      the uptake of biosimilars, and review of some biosimilars in development for
      oncology indications. 

PMID- 25621391
TI  - The (ir)relevance of procedural justice in the pathways to crime.
AB  - Process-based approaches to compliance argue that normative considerations, such
      as procedural justice and legitimacy, have the potential to reduce offending.
      This perspective was formalized with Tyler's (1990, 2003) Model of Procedural
      Justice and subsequently was evaluated among adult and adolescent offenders
      alike. However, extant evaluations do not consider whether and how individual
      offending histories affect the relevance of the concepts of procedural justice
      and legitimacy on offending behavior. This void is problematic given the growing
      concern that judgments of procedural justice and perceived legitimacy may not
      always be relevant with respect to compliance (Tyler & Jackson, 2013). This
      research integrates a developmental perspective with the procedural justice model
      to evaluate the effects of procedural justice and legitimacy on offending among
      early-onset and adolescent-onset offenders. Using a sample of convicted
      adolescent offenders, evidence suggests that the relevance of the procedural
      justice model varies across age of onset. The normative considerations of
      procedural justice and legitimacy are unrelated to recidivism among early-onset
      offenders, yet they affect subsequent offending among adolescent-onset offenders,
      although not always in the direction specified by theory.

PMID- 25621393
TI  - Breastfeeding medicine: a bright future.

PMID- 25621395
TI  - Insertion of benzonitrile into Al-N and ga-N bonds: formation of fused
      carbatriaza-gallanes/alanes and their subsequent synthesis from amidines and
      trimethyl-gallium/aluminum.
AB  - Insertion of aromatic nitriles into Al-N and Ga-N bonds are reported. Sterically
      less hindered aluminum amide [PhNHAlMe2]2 (1) undergoes C=N insertion with
      benzonitrile to give an isomeric mixture of tetracyclic triazaalanes
      {[PhNC(Ph)N]3[PhNC(Ph)NH]Al[AlMe][AlMe2]2} (2 and 3). A similar reaction with
      analogous gallium amide affords a tetracyclic triazagallane
      {[PhNC(Ph)N]3[PhNC(Ph)NH]Ga[GaMe][GaMe2]2} (6) along with a novel bowl shaped
      carbon containing Ga-N cluster {[PhNC(Ph)N][PhN][GaMe]2}3 (5). On the other hand,
      when sterically bulky gallium amide (Dipp on N, Dipp = 2,6-diisopropylphenyl) is
      employed, a tetrameric gallium amidinate {[(Dipp)NC(Ph)N]GaMe}4 (8) is obtained.
      Tetracyclic triazagallazane 6 is also synthesized from the condensation reaction
      of N-phenylbenzamidine with GaMe3.OEt2. Unlike AlMe3, this reaction produces only
      one isomer. In case of amidines with bulkier substituents on N such as Dipp,
      formation of a bicyclic triazagallane {[(Dipp)NC(Ph)NH]2[(Dipp)NC(Ph)N][GaMe]2}
      (14) is also observed along with tetrameric gallium amidinate 8, whereas N-tert
      butylbenzamidine affords exclusively a tetrameric gallium amidinate {[(tert
      Bu)NC(Ph)N]GaMe}4 (15) similar to its Al analogue. However, treating N
      (Dipp)acetamidine with GaMe3.OEt2 gives only a bicyclic triazagallane
      {[(Dipp)NC(Me)NH]2[(Dipp)NC(Me)N][GaMe]2} (16). An intermediate [(tert-Bu)N(H)
      C(Ph)NGaMe2]2 (17), which is involved in the formation of tetrameric gallium
      amidinate 15, is also characterized. A comparison of the structural parameters of
      Ga-N-C and Al-N-C frameworks synthesized in this study is reported. 

PMID- 25621392
TI  - Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas.
AB  - Chordomas are an aggressive rare type of malignant bone tumors arising from the
      remnant of the notochord. Chordomas occur mainly in vertebral bones and account
      for 1-4% of malignant bone tumors. Management and treatment of chordomas are
      difficult as they are resistant to conventional chemotherapy; therefore, they are
      mainly treated with surgery and radiation therapy. In this study, we performed
      DNA methylation profiling of 26 chordomas and normal nucleus pulposus samples
      plus UCH-1 chordoma cell line using the Illumina Infinium HumanMethylation450
      BeadChips. Combined bisulfite restriction analysis and bisulfite sequencing was
      used to confirm the methylation data. Gene expression was analyzed using RT-PCR
      before and after 5-aza-2'-deoxycytidine (5-azaDC) treatment of chordoma cell
      lines. Analysis of the HumanMethylation450 BeadChip data led to the
      identification of 8,819 loci (2.9%) that were significantly differentially
      methylated (>0.2 average beta-value difference) between chordomas and nucleus
      pulposus samples (adjusted P < 0.05). Among these, 5,868 probes (66.5%) were
      hypomethylated, compared to 2,951 (33.5%) loci that were hypermethylated in
      chordomas compared to controls. From the 2,951 differentially hypermethylated
      probes, 33.3% were localized in the promoter region (982 probes) and, among
      these, 104 probes showed cancer-specific hypermethylation. Ingenuity Pathway
      Analysis indicates that the cancer-specific differentially methylated loci are
      involved in various networks including cancer disease, nervous system development
      and function, cell death and survival, cellular growth, cellular development, and
      proliferation. Furthermore, we identified a subset of probes that were
      differentially methylated between recurrent and non-recurrent chordomas. BeadChip
      methylation data was confirmed for these genes and gene expression was shown to
      be upregulated in methylated chordoma cell lines after treatment with 5-azaDC.
      Understanding epigenetic changes in chordomas may provide insights into chordoma
      tumorigenesis and development of epigenetic biomarkers.

PMID- 25621396
TI  - Transcriptional and cellular responses of the green alga Chlamydomonas
      reinhardtii to perfluoroalkyl phosphonic acids.
AB  - Perfluoroalkyl phosphonic acids (PFPAs), a new class of perfluoroalkyl substances
      used primarily in the industrial sector as surfactants, were recently detected in
      surface water and wastewater treatment plant effluents. Toxicological effects of
      PFPAs have as yet not been investigated in aquatic organisms. The objective of
      the present study was to evaluate the effects of perfluorooctylphosphonic acid
      (C8-PFPA) and perfluorodecylphosphonic acid (C10-PFPA) exposure (31-250MUg/L) on
      Chlamydomonas reinhardtii using genomic (qRT-PCR), biochemical (reactive oxygen
      species production (ROS) and lipid peroxidation), and physiological (cellular
      viability) indicators. After 72h of exposure, no differences were observed in
      cellular viability for any of the two perfluorochemicals. However, increase in
      ROS concentrations (36% and 25.6% at 125 and 250MUg/L, respectively) and lipid
      peroxidation (35.5% and 35.7% at 125 and 250MUg/L, respectively) was observed
      following exposure to C10-PFPA. C8-PFPA exposure did not impact ROS production
      and lipid peroxidation in algae. To get insights into the molecular response and
      modes of action of PFPA toxicity, qRT-PCR-based assays were performed to analyze
      the transcription of genes related to antioxidant responses including superoxide
      dismutase (SOD-1), glutathione peroxidase (GPX), catalase (CAT), glutathione S
      transferase (GST), and ascorbate peroxidase (APX I). Genomic analyses revealed
      that the transcription of CAT and APX I was up-regulated for all the C10-PFPA
      concentrations. In addition, PFPAs were quantified in St. Lawrence River surface
      water samples and detected at concentrations ranging from 250 to 850pg/L for C8
      PFPA and 380 to 650pg/L for C10-PFPA. This study supports the prevalence of PFPAs
      in the aquatic environment and suggests potential impacts of PFPA exposure on the
      antioxidant defensive system in C. reinhardtii. 

PMID- 25621397
TI  - Occurrence and origin of sensitivity toward difenoconazole in zebrafish (Danio
      reio) during different life stages.
AB  - We report here an investigation of the mechanisms contributing to the divergent
      sensitivity toward the triazole fungicide difenoconazole of zebrafish (Danio
      reio) during different life stages. Adult and embryonic zebrafish were exposed to
      three different concentrations of difenoconazole (0.01, 0.5 and 1.0mg/L). The
      death rate, bioaccumulation of difenoconazole, oxidative stress parameters and
      transcription of related genes were tested at 4 and 8 days post-exposure (dpe).
      The death rate for adult zebrafish was much higher than that of the embryos at an
      exposure concentration of 1.0mg/L at both 4 and 8 dpe. The concentrations of
      difenoconazole in both the embryos and adult fish were similar, except for the
      group exposed to 0.01mg/L difenoconazole. A decrease in antioxidant enzyme
      activities was observed in both the embryos and the livers of adult fish after
      exposure to difenoconazole. Significant lipid peroxidation was found in the
      livers of adult fish in all exposure groups at 8 dpe, but was not observed in the
      treated embryos. The gene transcription response of the embryos toward
      difenoconazole was different from that in the livers of adult fish at 4 dpe. At 8
      dpe, the modification in the transcription of the tested genes in the embryos and
      adult fish was similar, except for the genes related to the synthesis of sterols.

PMID- 25621398
TI  - Chronic effects of clofibric acid in zebrafish (Danio rerio): a multigenerational
      study.
AB  - Clofibric acid (CA) is an active metabolite of the blood lipid lowering agent
      clofibrate, a pharmaceutical designed to work as agonist of peroxisome
      proliferator-activated receptor alpha (PPARa). It is the most commonly reported
      fibrate in aquatic environments with low degradation rate and potential
      environmental persistence. Previous fish exposures showed that CA may impact
      spermatogenesis, growth and the expression of fat binding protein genes. However,
      there are limited data on the effects of chronic multigenerational CA exposures.
      Here, we assessed chronic multigenerational effects of CA exposure using
      zebrafish (Danio rerio) as a teleost model. Zebrafish were exposed through the
      diet to CA (1 and 10mg/g) during their whole lifetime. Growth, reproduction
      related parameters and embryonic development were assessed in the exposed fish
      (F1 generation) and their offspring (F2 generation), together with muscle
      triglyceride content and gonad histology. In order to study the potential
      underlying mechanisms, the transcription levels of genes coding for enzymes
      involved in lipid metabolism pathways were determined. The results show that
      chronic life-cycle exposure to CA induced a significant reduction in growth of F1
      generation and lowered triglyceride muscle content (10mg/g group). Also, an
      impact in male gonad development was observed together with a decrease in the
      fecundity (10mg/g group) and higher frequency of embryo abnormalities in the
      offspring of fish exposed to the lowest CA dose. The profile of the target genes
      was sex- and tissue-dependent. In F1 an up-regulation of male hepatic pparaa,
      pparb and acox transcript levels was observed, suggesting an activation of the
      fatty acid metabolism (provided that transcript level change indicates also a
      protein level change). Interestingly, the F2 generation, raised with control
      diet, displayed a response pattern different from that observed in F1, showing an
      increase in weight in the descendants of CA exposed fish, in comparison with
      control animals, which points to a multigenerational effect. 

PMID- 25621399
TI  - Immunological and physiological responses of the periwinkle Littorina littorea
      during and after exposure to the toxic dinoflagellate Alexandrium minutum.
AB  - Species of the dinoflagellate genus Alexandrium produce phycotoxins responsible
      for paralytic shellfish poisoning. Blooms of Alexandrium minutum reach very high
      concentrations of vegetative cells in the water column; and when these blooms
      occur, large numbers of toxic cysts can be produced and deposited on sediments
      becoming available to benthic species. The present study investigated the
      potential effect of exposure to toxic cysts of A. minutum on the periwinkle
      Littorinalittorea. Snails were exposed for nine days to pellicle cysts of toxic
      and non-toxic dinoflagellates, A. minutum and Heterocapsa triquetra,
      respectively, followed by six days of depuration while they were fed only H.
      triquetra. Toxin accumulation, condition index, immune and histopathological
      responses were analyzed. Histological alterations were also monitored in snails
      exposed to a harmful A. minutum bloom, which naturally occurred in the Bay of
      Brest. Snails exposed to toxic cysts showed abnormal behavior that seems to be
      toxin-induced and possibly related to muscle paralysis. Periwinkles accumulated
      toxins by preying on toxic cysts and accumulation appeared dependent on the time
      of exposure, increasing during intoxication period but tending to stabilize
      during depuration period. Toxic exposure also seemed to negatively affect
      hemocyte viability and functions, as ROS production and phagocytosis.
      Histological analyses revealed that toxic exposure induced damages on digestive
      organs of snails, both in laboratory and natural systems. This study demonstrates
      that an exposure to the toxic dinoflagellate A. minutum leads to sublethal
      effects on L. littorea, which may alter individual fitness and increase the
      susceptibility of snails to pathogens and diseases. 

PMID- 25621400
TI  - Neo-Marxian social class inequalities in the mental well-being of employed men
      and women: the role of European welfare regimes.
AB  - The relation between "neo-Marxian" social class (NMSC) and health in the working
      population has received considerable attention in public health research.
      However, less is known about the distribution of mental well-being according to
      NMSC in a European context. The objectives of this study are (i) to analyse the
      association of mental well-being and NMSC among employees in Europe (using a
      welfare regime typology), (ii) to investigate whether the relation between NMSC
      and mental well-being is the same in women compared to men within each welfare
      regime, and (iii) to examine within each welfare regime the role of the gender
      division of labour and job quality as potential mediating factors in explaining
      this association. Data from the European Social Survey Round 5 (2010) were
      analysed. Mental well-being was assessed by the WHO Well-being Index. Social
      class was measured through E.O. Wright's social class scheme. Models separated by
      sex were generated using Poisson regression with a robust error variance. The
      associations were presented as prevalence ratios with 95% confidence intervals.
      Women reported NMSC differences in mental well-being in State corporatist/family
      support and Southern welfare regimes. Men reported NMSC differences in mental
      well-being in all but the Basic security/market-oriented welfare regimes. Gender
      inequalities were more marked and widespread in Basic security/market-oriented
      welfare regimes. In all welfare regimes job quality (partly) explained NMSC
      inequalities in mental well-being for men, the role of the gender division of
      labour was unclear. This study showed that the relationship between NMSC and
      mental well-being among employees differs by gender and welfare regimes. It
      confirms the importance of NMSC and welfare regimes to explain gender and social
      class inequalities in mental well-being. 

PMID- 25621401
TI  - 'Who's the guy in the room?' Involving fathers in antenatal care screening for
      sickle cell disorders.
AB  - Fathers are increasingly invited to take part in antenatal care of which
      screening for sickle cell trait is a part. Expectations about involvement reflect
      changing perceptions of fatherhood and negotiation of gendered identities.
      Current policy supports male involvement, but is less clear on what basis and
      with what consequences. In exploring this, our qualitative study, using semi
      structured interviews, presents the experiences of fathers who have recently
      undergone antenatal screening for sickle cell. The sample was generated in
      discussion with eight non-governmental organisations. We recruited 24 fathers
      from nine UK cities. Our analysis outlines the importance of 'presence', in which
      fathers rely on nurturing definitions of fatherhood to display their sense of
      responsibility. Fathers, however, struggled to find a meaningful role as
      traditional masculinities became juxtaposed with new and complex forms of gender
      organisation, creating the potential for estrangement. To conclude, screening
      policy makes an appeal to emergent masculinities. It also generates risks and
      compromises choice, due to the normative values implicit in the screening
      process, reinforced by the more controlling aspects of health surveillance. This
      creates confusion among fathers, who are not sure why they have been invited into
      the antenatal space. 

PMID- 25621402
TI  - Examining the relationship between social support availability, urban center
      size, and self-perceived mental health of recent immigrants to Canada: a mixed
      methods analysis.
AB  - The experiences of settlement in a new country (e.g., securing housing and
      employment, language barriers) pose numerous challenges for recent immigrants
      that can impede their health and well-being. Lack of social support upon arrival
      and during settlement may help to explain why immigrant mental health status
      declines over time. While most urban centers in Canada offer some settlement
      services, little is known about how the availability of social supports, and the
      health statuses of recent immigrants, varies by city size. The objective of this
      mixed-methods study was to examine the relationship between self-perceived mental
      health (SPMH), social support availability, and urban center size, for recent
      immigrants to Canada. The quantitative component involved analysis of 2009-2010
      Canadian Community Health Survey data, selecting for only recent immigrants and
      for those living in either large or small urban centers. The qualitative
      component involved in-depth interviews with managers of settlement service
      organizations located in three large and three small urban centers in Canada. The
      quantitative analysis revealed that social support availability is positively
      associated with higher SPMH status, and is higher in small urban centers. In
      support of these findings, our interviews revealed that settlement service
      organizations operating in small urban centers offer more intensive social
      supports; interviewees attributed this difference to personal relationships in
      small cities, and the ease with which they can connect to other agencies to
      provide clients with necessary supports. Logistic regression analysis revealed,
      however, that recent immigrants in small urban centers are twice as likely to
      report low SPMH compared to those living in large urban centers. Thus, while the
      scope and nature of settlements services appears to vary by city size in Canada,
      more research is needed to understand what effect settlement services have on the
      health status of recent immigrants to Canada, especially in smaller urban
      centers. 

PMID- 25621403
TI  - A model for common ground development to support collaborative health
      communities.
AB  - Common ground is necessary for developing collaboration as part of building
      resilience for public health preparedness. While the importance of common ground
      as an essential component of collaboration has been well described, there is a
      need for studies to identify how common ground develops over time, across
      individual and group dimensions, and the contexts that influence its development.
      This paper studied common ground development in three Canadian communities
      between October 2010 and March 2011 through a project on capacity building for
      disaster management. Disaster management requires the integration of paid and
      volunteer participants across public and private sectors and is therefore a good
      domain to study common ground development. We used directed qualitative content
      analysis to develop a model of common ground development over time that describes
      its progression through coordinative, cooperative and collaborative common
      ground. We also identified how common ground develops at micro (individual) and
      macro (group) levels, as well as how agency, technology and geographical contexts
      influence its development. We then use the four phases of disaster management to
      illustrate how our model can support longitudinal common ground development. Our
      findings provide useful insight to enable proactive development of common ground
      in collaborative health communities. 

PMID- 25621404
TI  - Kinetic and thermodynamic origins of osmolyte-influenced nucleic acid folding.
AB  - The influential role of monovalent and divalent metal cations in facilitating
      conformational transitions in both RNA and DNA has been a target of intense
      biophysical research efforts. However, organic neutrally charged cosolutes can
      also significantly alter nucleic acid conformational transitions. For example,
      highly soluble small molecules such as trimethylamine N-oxide (TMAO) and urea are
      occasionally utilized by organisms to regulate cellular osmotic pressure.
      Ensemble studies have revealed that these so-called osmolytes can substantially
      influence the thermodynamics of nucleic acid conformational transitions. In the
      present work, we exploit single-molecule FRET (smFRET) techniques to measure, for
      first time, the kinetic origins of these osmolyte-induced changes to the folding
      free energy. In particular, we focus on smFRET RNA and DNA constructs designed as
      model systems for secondary and tertiary structure formation. These findings
      reveal that TMAO preferentially stabilizes both secondary and tertiary
      interactions by increasing kfold and decreasing kunfold, whereas urea
      destabilizes both conformational transitions, resulting in the exact opposite
      shift in kinetic rate constants (i.e., decreasing kfold and increasing kunfold).
      Complementary temperature-dependent smFRET experiments highlight a thermodynamic
      distinction between the two different mechanisms responsible for TMAO-facilitated
      conformational transitions, while only a single mechanism is seen for the
      destabilizing osmolyte urea. Finally, these results are interpreted in the
      context of preferential interactions between osmolytes, and the solvent
      accessible surface area (SASA) associated with the (i) nucleobase, (ii) sugar,
      and (iii) phosphate groups of nucleic acids in order to map out structural
      changes that occur during the conformational transitions. 

PMID- 25621405
TI  - Does clinical experience affect the reproducibility of cervical vertebrae
      maturation method?
AB  - OBJECTIVE: To assess interobserver and intraobserver reproducibility of the
      cervical vertebrae maturation method (CVMM) among three panels of judges with
      different levels of orthodontic experience (OE). MATERIALS AND METHODS: Fifty
      individual lateral cephalograms of good quality with complete visualization of
      cervical vertebrae 1 to 4 were selected. Thirty clinicians, divided according to
      their OE into three groups (junior group, JU, OE <= 1 year; postgraduate group,
      PG, 2 <= OE <= 4 years; specialist group, SP, OE >= 7 years), evaluated the
      cephalograms in two sessions (T1 and T2) at 3 weeks apart. Kendall's W and
      weighted Cohen's kappa (kappa) coefficients were performed to assess
      interobserver and intraobserver agreement. The level of significance was set as P
      < .05. For both the interobserver and the intraobserver datasets, the percentage
      of perfect agreement (PPA) and the number of stages apart for each disagreement
      were calculated. RESULTS: Kendall's W at T1 was SP  =  0.61, PG  =  0.70, and JU 
      =  0.87; at T2 it was SP  =  0.78, PG  =  0.85, and JU  =  0.86. The percentage
      of total interobserver perfect agreement (Inter-PPA) was 42.3% at T1 and 46.3% at
      T2. The JU group had the highest Cohen's kappa coefficient at 0.78, while the PG
      and SP had coefficients of 0.64 each. The percentage of total intraobserver
      perfect agreement (Intra-PPA) was 54.2%. CONCLUSIONS: The reproducibility of the
      method was not improved by the level of orthodontic experience. The group with
      the lowest level of orthodontic experience had the best performance.

PMID- 25621406
TI  - International note: Teen users' problematic online behavior: using panel data
      from South Korea.
AB  - The purpose of this study was to identify factors of teen users' problematic
      online behaviors using data from the Korea Youth Panel Survey (KYPS) collected
      over a four-year period. Problematic online behaviors included unauthorized ID
      use, disguising one's age or gender while chatting online, and cursing/insulting
      someone in a chat room or on a bulletin board. Results from the panel data
      analyses showed that many adolescents explored and discontinued engaging in
      online delinquency as they got older. Respondents' offline behaviors and self
      control were significantly associated with problematic online behaviors,
      supporting the importance of internal traits. Peer effects were consistently more
      important than parental effects on teen's online delinquency. Increases in time
      spent using a computer also contributed to the likelihood of problematic online
      behaviors. 

PMID- 25621407
TI  - Serum Tau Fragments Predict Return to Play in Concussed Professional Ice Hockey
      Players.
AB  - The diagnosis of sports-related concussion is mainly based on subjective clinical
      symptoms and neuropsychological tests. Therefore, reliable brain injury
      biomarkers to assess when it is safe to return to play are highly desirable. The
      overall objective of this study was to evaluate the utility of two newly
      described tau fragments for diagnosis and prognosis of sports-related
      concussions. This multi-center prospective cohort study involved all 12 teams of
      the top professional ice hockey league in Sweden. A total of 288 players
      consented to participate in the study. Thirty-five players sustained concussions,
      of whom 28 underwent repeated blood samplings at 1, 12, 36, and 144 h after the
      trauma, or when the player returned to play (7 to >90 days). There was no
      significant increase in the levels of Tau-A in post-concussion samples compared
      with preseason values. However, serum levels of Tau-C were significantly higher
      in post-concussion samples compared with preseason. Further, levels of Tau-A
      correlated with the duration of post-concussive symptoms. Tau-A in serum, which
      is newly discovered biomarker, could be used to predict when it is safe to return
      to play after a sports-related concussion.

PMID- 25621408
TI  - A modified technique to reduce spillage and the operative time in laparoscopic
      dermoid cyst excision.
AB  - INTRODUCTION: To determine whether controlled drilling, cyst excision, and
      removal in a bag can reduce the operative time and intraperitoneal spillage in
      dermoid cysts. MATERIALS AND METHODS: Laparoscopic dermoid cyst excision was
      performed in 45 women using a different technique: controlled drilling of dermoid
      cysts in a bag, excision of these cysts, and their removal in the same bag.
      RESULTS: The median age of the patients was 29.5 years (range, 18-42 years), the
      median size of the cysts was 55 mm (range, 30-100 mm), the median operative time
      was 40 minutes (range, 25-60 minutes), the median level of cancer antigen 19-9
      was 28.5 U/mL (range, 1.2-127 U/mL), the median parity was 1 (range, 0-3), and
      the median hospitalization time was 1 day (range, 1-2 days). Twenty-five cysts
      were in the right ovary, and 20 were in the left ovary. In all cases, the dermoid
      cysts were ruptured with the controlled drilling. There was no intraperitoneal
      spillage of the cyst contents in the abdomen. No complication occurred
      intraoperatively or postoperatively. There was no recurrence 3 months after the
      operation. CONCLUSIONS: Controlled drilling, excision, and removal of a dermoid
      cyst inside the same bag seems to be a feasible method to prevent intraperitoneal
      spillage and to reduce the operative time.

PMID- 25621409
TI  - Adjuvant carboplatin, paclitaxel, and vaginal cuff brachytherapy for stage III
      endometrial cancer: analysis of outcomes and patterns of recurrence based on
      pathologic characteristics.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes of patients with stage
      III endometrial adenocarcinoma treated with surgery followed by adjuvant
      chemotherapy and vaginal cuff brachytherapy. METHODS: We retrospectively
      identified 83 patients treated for 1988 International Federation of Gynecology
      and Obstetrics (FIGO) stage III endometrial adenocarcinoma at our institution
      between 2003 and 2010. All patients underwent comprehensive surgical staging.
      Adjuvant therapy was carboplatin and paclitaxel for 6 cycles and vaginal cuff
      brachytherapy. For analysis, patients were grouped into type I (FIGO grade 1-2
      endometrioid histology, n = 41) or type II (FIGO grade 3, clear cell or papillary
      serous histology, n = 42) disease. Forty-three patients (52%) had node-positive
      disease, with similar node-positive rates for type I (n = 21, 51.2%) and type II
      (n = 22, 52.4%). RESULTS: The median follow-up was 38.6 months. There were no
      isolated vaginal failures. The estimated 3-year disease-free survival (DFS) and
      overall survival (OS) for type I versus type II were 92.4% versus 58.0% (P =
      0.001) and 97.2% versus 65.8% (P = 0.002), respectively. The 3-year DFS and OS
      for node negative versus node positive were 85.0% versus 63.6% (P = 0.02) and
      84.2% versus 78.0% (P = 0.02), respectively. Associations between type I
      histology and node-negative disease with improved DFS and OS persisted on
      multivariate analysis. CONCLUSIONS: Our institutional approach of adjuvant
      chemotherapy and vaginal cuff brachytherapy for stage III endometrial cancer
      seemed acceptable for patients with low-risk histology or node-negative disease.
      In contrast, higher rates of failure among those with high-risk histology and/or
      node-positive disease support intensification of therapy in these subsets.

PMID- 25621410
TI  - Lower limb lymphedema and neurological complications after lymphadenectomy for
      gynecological cancer.
AB  - OBJECTIVE: Lymphadenectomy is a frequent procedure for surgical staging of
      gynecological malignancies. Nevertheless, minor complications, such as lower limb
      lymphedema (LLL) and neurological complications (NCs), after pelvic and aorto
      caval lymphadenectomy still remain underinvestigated. The present study considers
      short-term and long-term incidence and risk factors for LLL and NC in patients
      with gynecological cancer who underwent lymphadenectomy. MATERIALS AND METHODS:
      In 2 different institutions, University of Turin and University of Lausanne, a
      total of 152 patients who received lymphadenectomy for endometrial, cervical, or
      ovarian cancer were retrospectively identified. During the follow-up, data about
      LLL and NC were collected by means of a questionnaire. Short-term and long-term
      incidence of LLL and NC was evaluated, and risk factors, such as age, body mass
      index, type of cancer, surgical approach, number and extension of the removed
      lymph nodes, presence of lymph node metastasis, and adjuvant treatments, were
      analyzed. RESULTS: Short-term incidence of LLL and NC after lymphadenectomy was
      high (36%) and predictive of long-term persistence. Between the analyzed risk
      factors, number of removed lymph nodes and adjuvant radiotherapy were
      significantly associated with an increased incidence of minor complications (P <
      0.05). CONCLUSIONS: Lower limb lymphedema and NC are more frequent than expected.
      They are related to the radicality of lymphadenectomy and adjuvant radiotherapy.
      They affect the quality of life of the patients treated for gynecological cancer
      and their perceptions of healing. Minor complications are commonly persistent and
      need a prompt diagnosis and a specialized management to improve their prognosis.

PMID- 25621411
TI  - Do Cell-Cycle Phase-Specific Markers Predict Disease Grade, Stage, and Outcome in
      Cervical Carcinoma?
AB  - AIMS: Multiparameter analysis of cell cycle markers has shown a strong
      relationship between cell cycle progression and tumor grade, stage, and clinical
      outcome in penile, renal, ovarian, and breast cancers. We sought to link
      expression of cell cycle phase-specific markers in cervical cancer to tumor
      grade, stage, and clinical outcome to investigate their potential use as
      prognostic and predictive markers. METHODS: Pretreatment biopsy material was
      obtained from 35 patients with cervical cancer (stage IB2-IVA) and 12 normal
      cervix control cases. Each patient was treated with neoadjuvant chemotherapy
      followed by chemoradiation. Immunohistochemical staining was performed using a
      panel of cell cycle phase markers: replication licensing factors: Mcm2
      (minichromosome maintenance 2) and geminin, and the standard proliferation marker
      Ki67 (clone MIB-1). RESULTS: The expression levels of each cell cycle biomarker
      were very high in all cases of squamous cell carcinoma of the cervix regardless
      of grade or stage of disease. In our cohort, all cases displayed an aggressive,
      so-called actively cycling phenotype. Univariate analysis showed that none of the
      cell cycle biomarkers predicted grade, stage, or clinical outcome. CONCLUSIONS:
      Cell cycle phase-specific markers do not appear to predict disease grade, stage,
      or outcome in our sample of patients with cervical cancer. This is not
      surprising, given that the expression of each cell cycle biomarker was very high
      in all cases.Indeed, all the cases of squamous cell carcinoma of the cervix (n =
      28) and all but 1 of the adenocarcinomas (n = 7) in this study displayed an
      aggressive "actively cycling" phenotype. This predominance of actively cycling
      tumors is unusual and may reflect the viral etiology underlying the disease.
      These preliminary findings raise many interesting questions including the
      prognostic value of disease grade and markers of proliferation in cervical tumors
      as reliable prognostic indicators. Further work on a larger cohort of patients is
      warranted.

PMID- 25621412
TI  - Interfering with memory for faces: The cost of doing two things at once.
AB  - We inferred the processes critical for episodic retrieval of faces by measuring
      susceptibility to memory interference from different distracting tasks.
      Experiment 1 examined recognition of studied faces under full attention (FA) or
      each of two divided attention (DA) conditions requiring concurrent decisions to
      auditorily presented letters. Memory was disrupted in both DA relative to FA
      conditions, a result contrary to a material-specific account of interference
      effects. Experiment 2 investigated whether the magnitude of interference depended
      on competition between concurrent tasks for common processing resources. Studied
      faces were presented either upright (configurally processed) or inverted
      (featurally processed). Recognition was completed under FA, or DA with one of two
      face-based distracting tasks requiring either featural or configural processing.
      We found an interaction: memory for upright faces was lower under DA when the
      distracting task required configural than featural processing, while the reverse
      was true for memory of inverted faces. Across experiments, the magnitude of
      memory interference was similar (a 19% or 20% decline from FA) regardless of
      whether the materials in the distracting task overlapped with the to-be
      remembered information. Importantly, interference was significantly larger (42%)
      when the processing demands of the distracting and target retrieval task
      overlapped, suggesting a processing-specific account of memory interference. 

PMID- 25621413
TI  - Molecular and biochemical characterization of Paragonimus westermani tyrosinase.
AB  - Trematode tyrosinases (TYRs) play a major role in the tanning process during
      eggshell formation. We investigated the molecular and biochemical features of
      Paragonimus westermani TYR (PwTYR). The PwTYR cDNA was composed of 1568-bp
      encompassing a 1422-bp-long open reading frame (474-amino acid polypeptide). A
      strong phylogenetic relationship with Platyhelminthes and Deuterostomian
      orthologues was evident. The recombinant PwTYR expressed in prokaryotic cells
      promptly oxidized diphenol substrates, with a preferential affinity toward ortho
      positioned hydroxyl groups. It demonstrated fairly weak activity for monophenol
      compounds. Diphenol oxidase activity was augmented with an increase of pH from
      5.0 to 8.0, while monophenol oxidase activity was highest at an acidic pH and
      gradually decreased as pH increased. Transcription profile of PwTYR was
      temporally upregulated along with worm development. PwTYR was specifically
      localized in vitellocytes and eggs. The results suggested that conversion of
      tyrosine to L-dihydroxyphenylalanine by PwTYR monophenol oxidase activity might
      be rate-limiting step during the sclerotization process of P. westermani eggs.
      The pH-dependent pattern of monophenol and diphenol oxidase activity further
      proposes that the initial hydroxylation might slowly but steadily progress in
      acidic secreted vesicles of vitellocytes and the second oxidation process might
      be rapidly accelerated by neural or weak alkaline pH environments within the
      ootype.

PMID- 25621414
TI  - Pore space partition by symmetry-matching regulated ligand insertion and dramatic
      tuning on carbon dioxide uptake.
AB  - Metal-organic frameworks (MOFs) with the highest CO(2) uptake capacity are
      usually those equipped with open metal sites. Here we seek alternative strategies
      and mechanisms for developing high-performance CO(2) adsorbents. We demonstrate
      that through a ligand insertion pore space partition strategy, we can create
      crystalline porous materials (CPMs) with superior CO(2) uptake capacity.
      Specifically, a new material, CPM-33b-Ni without any open metal sites, exhibits
      the CO(2) uptake capacity comparable to MOF-74 with the same metal (Ni) at 298 K
      and 1 bar.

PMID- 25621415
TI  - Relationship between activation volume and polymer matrix effects on photochromic
      performance: bridging molecular parameter to macroscale effect.
AB  - Photochromic compounds have attracted attention as ophthalmic lenses because of
      their reversible color modulation upon irradiation with light. However, the
      efficiency of the photochromism is strongly affected by their surrounding because
      of the structural changes concomitant with the photochromism, which causes the
      decrease in the photochromic performance in the polymer matrix. Therefore, the
      clarification of the degree of the structural changes is necessary to apply to
      the ophthalmic lenses. Bridged imidazole dimers are one of the fast photoswitch
      molecules possessing high photochromic quantum yield and durability. Although the
      enhancement of the photochromic properties of bridged imidazole dimers has been
      vigorously studied, the quantitative information about the structural changes has
      not been revealed in detail. In this study, we investigated the pressure effects
      on the photochromic properties of bridged imidazole dimers. The activation volume
      for the thermal back-reaction of the photogenerated biradical species becomes an
      effective measure to predict the degree of the structural change during the
      photochromic reaction. We revealed that the smaller activation volume is suitable
      for keeping the efficient photochromic reaction in the polymer matrix because the
      photochromic reaction is not affected by the surroundings. These fundamental
      insights into the molecular dynamics provide valuable information to develop fast
      photochromic compounds that are suitable for the use in the polymer matrix and
      pressure sensitive photochromic materials. 

PMID- 25621417
TI  - Cognitive control moderates the association between emotional instability and
      alcohol dependence symptoms.
AB  - Previous research has linked emotional instability with problematic alcohol use.
      This may be a function of increased "hot" information processing (which is
      relatively automatic in nature and highly influenced by emotional states) for
      individuals with more emotional instability. According to dual-process models,
      cognitive control may attenuate the impact of emotional instability by preventing
      an overreliance on hot information processing. It was hypothesized that emotional
      instability would be positively associated with alcohol-related consequences, but
      that cognitive control would moderate this association. Participants were
      undergraduate students (n = 80) who endorsed drinking at moderate levels.
      Participants completed laboratory assessments of emotional instability, alcohol
      use and its consequences, and cognitive control. An observed variable path model
      examined the association between emotional instability and alcohol problems.
      Consistent with hypotheses, emotional instability was positively associated with
      alcohol consequences, and this relationship was moderated by cognitive control,
      at least for dependence symptoms. At low levels of cognitive control, there was a
      positive association between emotional instability and dependence symptoms (beta
      = 0.514, p < .001), however, this association was attenuated and no longer
      significant at high levels of cognitive control (beta = 0.095, p = .302).
      Emotional instability may promote alcohol dependence via an overreliance on hot
      information processing. Consistent with dual-process theory, this relationship is
      diminished among individuals with more cognitive control. Interventions focusing
      on increasing cognitive control may be effective in reducing alcohol pathology
      associated with emotional instability. (PsycINFO Database Record 

PMID- 25621416
TI  - Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking
      reinforcement motives, and affective responses.
AB  - Nicotine dependence has been suggested to be related to reinforcement
      sensitivity, which encompasses behavioral predispositions either to avoid
      aversive (behavioral inhibition) or to approach appetitive (behavioral
      activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use
      and offer potential targets for personalized smoking cessation therapy. However,
      little is known regarding how reinforcement sensitivity is related to
      motivational processes implicated in the maintenance of smoking. Additionally,
      women and men differ in reinforcement sensitivity, and such difference may cause
      distinct relationships between reinforcement sensitivity and motivational
      processes for female and male smokers. In this study, the authors characterized
      reinforcement sensitivity in relation to affect, smoking-related reinforcement
      motives, and affective responses, using self-report and psychophysiological
      measures, in over 200 smokers before treating them. The Behavioral
      Inhibition/Activation Scales (BIS/BAS; Carver & White, 1994) was used to measure
      reinforcement sensitivity. In female and male smokers, BIS was similarly
      associated with negative affect and negative reinforcement of smoking. However,
      positive affect was positively associated with BAS Drive scores in male smokers,
      and this association was reversed in female smokers. BIS was positively
      associated with corrugator electromyographic reactivity toward negative stimuli
      and left frontal electroencephalogram alpha asymmetry. Female and male smokers
      showed similar relationships for these physiological measures. These findings
      suggest that reinforcement sensitivity underpins important motivational processes
      (e.g., affect), and gender is a moderating factor for these relationships. Future
      personalized smoking intervention, particularly among more dependent treatment
      seeking smokers, may experiment to target individual differences in reinforcement
      sensitivity. (PsycINFO Database Record 

PMID- 25621418
TI  - The effects of repeated exposure to graphic fear appeals on cigarette packages: A
      field experiment.
AB  - Experimental studies on the effects of graphic fear appeals on cigarette packages
      typically expose smokers in a single session to a fear appeal, although in
      practice the exposure is always repeated. The present study applied an improved
      study design with repeated exposure to fear appeals on cigarette packages. In
      this field-experiment, 118 smokers were assigned to 1 of 2 conditions with either
      graphic fear appeals or textual warnings on their cigarette packages. During 3
      weeks, fear and disgust were assessed 6 times. The intention to quit smoking
      after 3 weeks and quitting activity during the 3 weeks were the dependent
      measures. The effects of 3 pretest individual difference moderators were tested:
      disengagement beliefs, number of cigarettes smoked a day, and readiness to quit.
      Three weeks of exposure to the graphic fear appeals led to a stronger intention
      to quit, but only when smokers scored low on disengagement beliefs, or were
      heavier smokers. In addition, smokers low in disengagement more often reported to
      have cut down on smoking in the graphic condition. There were no indications of
      habituation of fear and disgust over the 3 weeks. The effects of graphic fear
      appeals depended on smokers' characteristics: The moderators may explain the
      mixed findings in the literature. The lack of habituation may be caused by the
      renewal of the graphics every few days. The used field-experimental design with
      natural repeated exposure to graphics is promising.

PMID- 25621419
TI  - Childhood cognitive measures as predictors of alcohol use and problems by mid
      adulthood in a non-Western cohort.
AB  - This study examined the relationship between childhood cognitive functioning and
      academic achievement and subsequent alcohol use and problems in a non-Western
      setting. We examined longitudinal data from a birth cohort sample (N = 1,795) who
      were assessed at age 11 years on cognitive measures and then approximately 25
      years later on lifetime alcohol use and alcohol use disorder symptom count. The
      sample was from Mauritius (eastern Africa), which allowed us to examine these
      relationships in a non-Western society with a different social structure than is
      typical of prior cognitive studies on primarily White samples in Western
      societies. Poorer performance on the Trail Making Test B-A in childhood predicted
      being a lifetime drinker, even after covarying for gender, childhood psychosocial
      adversity, and Muslim religion. Lower academic achievement and verbal IQ, but not
      performance IQ, were predictive of subsequent alcohol problems after including
      demographic covariates; the relationship between verbal IQ and alcohol problems
      was stronger in females than males. A nonlinear relationship emerged for Trails,
      suggesting that only more extreme impairment on this measure was indicative of
      later alcohol problems. Results of this study provide evidence that verbal
      deficits and poor academic performance exist in a general cohort sample by age 11
      years (when 99% were nondrinkers) for those who go on to develop alcohol
      problems. (PsycINFO Database Record 

PMID- 25621420
TI  - Variability in and agreement between modeled and personal continuously measured
      black carbon levels using novel smartphone and sensor technologies.
AB  - Novel technologies, such as smartphones and small personal continuous air
      pollution sensors, can now facilitate better personal estimates of air pollution
      in relation to location. Such information can provide us with a better
      understanding about whether and how personal exposures relate to residential air
      pollution estimates, which are normally used in epidemiological studies. The aims
      of this study were to examine (1) the variability in personal air pollution
      levels during the day and (2) the relationship between modeled home and school
      estimates and continuously measured personal air pollution exposure levels in
      different microenvironments (e.g., home, school, and commute). We focused on
      black carbon as an indicator of traffic-related air pollution. We recruited 54
      school children (aged 7-11) from 29 different schools around Barcelona as part of
      the BREATHE study, an epidemiological study of the relation between air pollution
      and brain development. For 2 typical week days during 2012-2013, the children
      were given a smartphone with CalFit software to obtain information on their
      location and physical activity level and a small sensor, the micro-aethalometer
      model AE51, to measure their black carbon levels simultaneously and continuously.
      We estimated their home and school exposure to PM2.5 filter absorbance, which is
      well-correlated with black carbon, using a temporally adjusted PM2.5 absorbance
      land use regression (LUR) model. We found considerable variation in the black
      carbon levels during the day, with the highest levels measured during commuting
      periods (geometric mean = 2.8 MUg/m(3)) and the lowest levels at home (geometric
      mean = 1.3 MUg/m(3)). Hourly temporally adjusted LUR model estimates for the home
      and school showed moderate to good correlation with measured personal black
      carbon levels at home and school (r = 0.59 and 0.68, respectively) and lower
      correlation with commuting trips (r = 0.32 and 0.21, respectively). The
      correlation between modeled home estimates and overall personal black carbon
      levels was 0.62. Personal black carbon levels vary substantially during the day.
      The correlation between modeled and measured black carbon levels was generally
      good, with the exception of commuting times. In conclusion, novel technologies,
      such as smartphones and sensors, provide insights in personal exposure to air
      pollution. 

PMID- 25621421
TI  - Electron transfer-induced coupling of haloarenes to styrenes and 1,1
      diphenylethenes triggered by diketopiperazines and Potassium tert-butoxide.
AB  - The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved
      with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In
      contrast to previously reported reactions where phenanthroline has been used to
      mediate the reactions, the use of diketopiperazines can lead to either 1,1,2
      triarylethenes or 1,1,2-triarylethanes, depending on the conditions used. 

PMID- 25621422
TI  - A redox-controllable molecular switch based on weak recognition of BPX26C6 at a
      diphenylurea station.
AB  - The Na+ ion-assisted recognition of urea derivatives by BPX26C6 has allowed the
      construction of a redox-controllable [2]rotaxane-type molecular switch based on
      two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize
      the triarylamine terminus into a corresponding radical cation attracted the
      macrocyclic component toward its adjacent carbamate station; subsequent addition
      of Zn powder moved the macrocyclic component back to its urea station. 

PMID- 25621423
TI  - Lectins: getting familiar with translators of the sugar code.
AB  - The view on the significance of the presence of glycans in glycoconjugates is
      undergoing a paradigmatic change. Initially mostly considered to be rather inert
      and passive, the concept of the sugar code identifies glycans as highly versatile
      platform to store information. Their chemical properties endow carbohydrates to
      form oligomers with unsurpassed structural variability. Owing to their capacity
      to engage in hydrogen (and coordination) bonding and C-H/pi-interactions these
      "code words" can be "read" (in Latin, legere) by specific receptors. A distinct
      class of carbohydrate-binding proteins are the lectins. More than a dozen protein
      folds have developed carbohydrate-binding capacity in vertebrates. Taking
      galectins as an example, distinct expression patterns are traced. The
      availability of labeled endogenous lectins facilitates monitoring of tissue
      reactivity, extending the scope of lectin histochemistry beyond that which
      traditionally involved plant lectins. Presentation of glycan and its cognate
      lectin can be orchestrated, making a glycan-based effector pathway in growth
      control of tumor and activated T cells possible. In order to unravel the
      structural basis of lectin specificity for particular glycoconjugates mimetics of
      branched glycans and programmable models of cell surfaces are being developed by
      strategic combination of lectin research with synthetic and supramolecular
      chemistry. 

PMID- 25621424
TI  - Synthesis, bioactivity, molecular docking and POM analyses of novel substituted
      thieno[2,3-b]thiophenes and related congeners.
AB  - Several series of novel substituted thienothiophene derivatives were synthesized
      by reacting the synthone 1 with different reagents. The newly synthesized
      compounds were characterized by means of different spectroscopic methods such as
      IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed
      significant activity against both Gram-positive and Gram negative bacteria, in
      addition to fungi. Molecular docking and POM analyses show the crucial role and
      impact of substituents on bioactivity and indicate the unfavorable structural
      parameters in actual drug design: more substitution doesn't guaranty more
      efficiency in bioactivity. 

PMID- 25621425
TI  - Multiplexed quantification for data-independent acquisition.
AB  - Data-independent acquisition (DIA) strategies provide a sensitive and
      reproducible alternative to data-dependent acquisition (DDA) methods for large
      scale quantitative proteomic analyses. Unfortunately, DIA methods suffer from
      incompatibility with common multiplexed quantification methods, specifically
      stable isotope labeling approaches such as isobaric tags and stable isotope
      labeling of amino acids in cell culture (SILAC). Here we expand the use of
      neutron-encoded (NeuCode) SILAC to DIA applications (NeuCoDIA), producing a
      strategy that enables multiplexing within DIA scans without further convoluting
      the already complex MS(2) spectra. We demonstrate duplex NeuCoDIA analysis of
      both mixed-ratio (1:1 and 10:1) yeast and mouse embryo myogenesis proteomes.
      Analysis of the mixed-ratio yeast samples revealed the strong accuracy and
      precision of our NeuCoDIA method, both of which were comparable to our
      established MS(1)-based quantification approach. NeuCoDIA also uncovered the
      dynamic protein changes that occur during myogenic differentiation, demonstrating
      the feasibility of this methodology for biological applications. We consequently
      establish DIA quantification of NeuCode SILAC as a useful and practical
      alternative to DDA-based approaches. 

PMID- 25621426
TI  - Evaluation of Health Plan Interventions to Influence Chronic Opioid Therapy
      Prescribing.
AB  - OBJECTIVES: Evaluate health plan interventions targeting physician chronic opioid
      therapy (COT) prescribing. MATERIALS AND METHODS: In 2006, Group Health's (GH)
      Integrated Group Practice (IGP) initiated diverse interventions targeting COT
      prescriber norms and practices. In 2010, the IGP implemented a COT guideline,
      including a mandated online course for physicians managing COT. These
      interventions were not implemented in GH's network practices. We compared trends
      in GH-IGP and network practices for 2006 to 2012 in the percent of patients
      receiving COT and their opioid dose. We compared physician beliefs before versus
      after the mandated course and precourse to postcourse changes in COT dosing for
      IGP physicians who took the course. RESULTS: From 2006 to 2012, mean (SE) daily
      opioid dose among IGP COT patients (intervention setting) declined from 74.1 mg
      (1.9 mg) morphine equivalent dose (MED) to 48.3 mg (1.0 mg) MED. Dose changes
      among GH network COT patients (control setting) were modest-88.2 mg (5.0 mg) MED
      in 2006 to 75.7 mg (2.3 mg) MED in 2012. Among physicians taking the mandated
      course in 2011, we observed precourse to postcourse changes toward more
      conservative opioid prescribing beliefs. However, COT dosing trends did not
      change precourse to postcourse. DISCUSSION: Following initiatives implemented to
      alter physician prescribing practices and norms, mean opioid dose prescribed to
      COT patients declined more in intervention than control practices. Physicians
      reported more conservative beliefs regarding opioid prescribing immediately after
      completing an online course in 2011, but the course was not associated with
      additional reductions in mean daily opioid dose prescribed by physicians
      completing the course.

PMID- 25621427
TI  - Does Classification of Chronic Musculoskeletal Disorder Patients Into
      Psychosocial Subgroups Predict Differential Treatment Responsiveness and 1-Year
      Outcomes After a Functional Restoration Program?
AB  - OBJECTIVES: The objectives of this study: (1) to assess whether Multidimensional
      Pain Inventory (MPI) profiles predicted differential responses to a functional
      restoration program (FRP) in chronic disabling occupational musculoskeletal
      disorder (CDOMD) patients; (2) to examine whether coping style improves following
      FRP; and (3) to determine whether discharge MPI profiles predict discharge
      psychosocial and 1-year socioeconomic outcomes. METHODS: Consecutive CDOMD
      patients (N=716) were classified into Adaptive Coper (AC, n=209), Interpersonally
      Distressed (ID, n=154), Dysfunctional (DYS, n=310), and Anomalous (n=43) using
      the MPI, and reclassified at discharge. Profiles were compared on psychosocial
      measures and 1-year socioeconomic outcomes. An intent-to-treat sample analyzed
      the effect of drop-outs on treatment responsiveness. RESULTS: The MPI
      classification significantly predicted program completion (P=0.001), although the
      intent-to-treat analyses found no significant effects of drop-out on treatment
      responsiveness. There was a significant increase in the number of patients who
      became AC or Anomalous at FRP discharge and a decrease in those who were ID or
      DYS. Patients who changed or remained as DYS at FRP discharge reported the
      highest levels of pain, disability, and depression. No significant interaction
      effect was found between MPI group and time for pain intensity or disability. All
      groups improved on psychosocial measures at discharge. DYS patients had decreased
      work retention and a greater health care utilization at 1 year. CONCLUSIONS: An
      FRP was clinically effective for CDOMD patients regardless of initial MPI
      profiles. The FRP modified profiles, with patients changing from negative to
      positive profiles. Discharge DYS were more likely to have poor 1-year outcomes.
      Those classified as Anomalous had a good prognosis for functional recovery
      similar to ACs.

PMID- 25621428
TI  - Pain Intensity, Headache Frequency, and the Behavioral Activation and Inhibition
      Systems.
AB  - OBJECTIVES: To test the hypothesized associations between measures of the
      behavioral inhibition system (BIS) and behavioral activation system (BAS) and
      both the intensity and frequency of pain. METHODS: A total of 563 college
      students were administered measures of BIS and BAS and asked to indicate both (1)
      the average intensity of pain at 10 body sites during the past week and (2) the
      frequency with which they experience mild, moderate, and severe headaches. The
      associations between (1) the BIS and BAS scale scores and (2) the worst average
      pain intensity experienced and headache frequencies were examined using a series
      of 1-way analyses of variance. RESULTS: As predicted, the measure of BIS
      demonstrated significant and nonlinear associations with both pain intensity and
      headache frequency. The measure of BAS was not significantly related to pain
      intensity, but did demonstrate a nonlinear association with the frequency of
      severe headaches. DISCUSSION: The findings are consistent with predictions based
      on a model hypothesizing that pain has a nonlinear impact on both BIS and BAS,
      with a stronger impact on BIS than BAS. If the current results are replicated in
      other samples, including samples of individuals with chronic pain, they have
      important implications for identifying biological factors that could influence
      pain and behavioral responses to pain, as well as for the development and
      evaluation of treatments that could enhance positive treatment outcomes.

PMID- 25621429
TI  - Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and
      Pharmacokinetic Dosing.
AB  - OBJECTIVES: (1) To quantify hydrocodone (HC) and hydromorphone (HM) metabolite
      pharmacokinetics with pharmacogenetics in CYP2D6 ultra-rapid metabolizer (UM),
      extensive metabolizer (EM), and poor metabolizer (PM) metabolizer phenotypes. (2)
      To develop an HC phenotype-specific dosing strategy for HC that accounts for HM
      production using clinical pharmacokinetics integrated with pharmacogenetics for
      patient safety. SETTING: In silico clinical trial simulation. PARTICIPANTS:
      Healthy white men and women without comorbidities or history of opioid, or any
      other drug or nutraceutical use, age 26.3+/-5.7 years (mean+/-SD; range, 19 to 36
      y) and weight 71.9+/-16.8 kg (range, 50 to 108 kg). MAIN OUTCOME MEASURES: CYP2D6
      phenotype-specific HC clinical pharmacokinetic parameter estimates and phenotype
      specific percentages of HM formed from HC. RESULTS: PMs had lower indices of HC
      disposition compared with UMs and EMs. Clearance was reduced by nearly 60% and
      the t1/2 was increased by about 68% compared with EMs. The canonical order for HC
      clearance was UM>EM>PM. HC elimination mainly by the liver, represented by ke,
      was reduced about 70% in PM. However, HC's apparent Vd was not significantly
      different among UMs, EMs, and PM. The canonical order of predicted plasma HM
      concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean
      predicted HM levels were within HM's therapeutic range, which indicates HC has
      significant phenotype-dependent pro-drug effects. CONCLUSIONS: Our results
      demonstrate that pharmacogenetics afford clinicians an opportunity to
      individualize HC dosing, while adding enhanced opportunity to account for its
      conversion to HM in the body.

PMID- 25621430
TI  - STAT3 association with microtubules and its activation are independent of HDAC6
      activity.
AB  - Signal transducer and activator of transcription 3 (STAT3) is an important
      oncogenic transcription factor residing in the cytoplasm in the resting cells.
      Upon stimulation, STAT3 is activated and translocated to the nucleus to regulate
      target genes. Although the canonical transcriptional function of STAT3 has been
      intensively studied, less is known about its cytoplasmic localization. In this
      study, by immunoprecipitation, microtubule cosedimentation, and
      immunofluorescence assays, we present the first evidence that cytoplasmic STAT3
      interacts with both tubulin and microtubules. By using small-molecule inhibitor
      approaches, we further demonstrate that the localization of STAT3 on microtubules
      and its activation are independent of histone deacetylase 6 (HDAC6) activity. In
      addition, disruption of microtubule dynamics does not alter the activation and
      nuclear translocation of STAT3 in response to interleukin-6 treatment. These
      findings reveal that cytoplasmic STAT3 is physically associated with
      microtubules, whereas its activation and nuclear translocation are independent of
      microtubule dynamics, implicating that the association of STAT3 with microtubules
      might be involved in the regulation of noncanonical functions of STAT3 in the
      cytoplasm. 

PMID- 25621431
TI  - Highly sensitive detection of CpG methylation in genomic DNA by AuNP-based
      colorimetric assay with ligase chain reaction.
AB  - We have developed a new ligase chain reaction-based colorimetric assay for
      detection of DNA methylation with ultrahigh sensitivity and selectivity. Using
      the proposed assay, as low as 0.01 fM methylated DNA can be detected by
      visualization of color changes of gold nanoparticles with the naked eye. 

PMID- 25621432
TI  - Early and late operation of cleft lip and intelligence quotient and psychosocial
      development in 3-7 years.
AB  - BACKGROUND: Early and late operations of the cleft lip represent exposure to
      general anesthesia during the first year of life. The early exposure to the
      anesthetics may influence long term neurological outcome. Timing of the operation
      may also influence the quality of life as babies with early repair might be
      accepted better by their families. AIMS: The aim of the study was to compare
      outcomes between two groups of patients operated on for the cleft lip in the
      first year of life. STUDY DESIGN: Observational cohort study. SUBJECTS: Early
      repair group included patients operated on in the first eight days of life and
      late repair group those operated on between 3 and 10 months. OUTCOME MEASURES:
      Intelligence quotient (IQ) and psychosocial development of children who were
      operated on for cleft lip were compared at the age of 3-7 years. RESULTS: No
      differences were found between early (n=15) and late (n=17) repair group in terms
      of IQ. In both IQ was within the normal range: 100.00 (SD 13.867), 98.76 (SD
      10.109), respectively. Significantly better results in physical functioning
      (P=0.042) and self-esteem (P=0.014) concepts in early repair group were found.
      CONCLUSIONS: We compared outcomes of two groups of patients operated on for cleft
      lip in the first year of life. The earlier anesthesia did not show a negative
      impact on intelligence quotient in 3-7 years compared to later anesthesia. The
      earlier repair of the cleft lip showed a significant positive impact on
      psychosocial development in 2 out of 13 concepts tested.

PMID- 25621433
TI  - Kinematic measurement of 12-week head control correlates with 12-month
      neurodevelopment in preterm infants.
AB  - BACKGROUND: Although new interventions treating neonatal brain injury show great
      promise, our current ability to predict clinical functional outcomes is poor.
      Quantitative biomarkers of long-term neurodevelopmental outcome are critically
      needed to gauge treatment efficacy. Kinematic measures derived from commonly used
      developmental tasks may serve as early objective markers of future motor
      outcomes. AIM: To develop reliable kinematic markers of head control at 12week
      corrected gestational age (CGA) from two motor tasks: head lifting in prone and
      pull-to-sit. STUDY DESIGN AND SUBJECTS: Prospective observational study of 22
      preterm infants born between 24 and 34weeks of gestation. OUTCOME MEASURES:
      Bayley Scales of Infant Development III (Bayley) motor scores. RESULTS:
      Intrarater and interrater reliability of prone head lift angles and pull-to-sit
      head angles were excellent. Prone head lift angles at 12week CGA correlated with
      white matter NAA/Cho, concurrent Test of Infant Motor Performance (TIMP) scores,
      and 12-month Bayley motor scores. Head angles during pull-to-sit at 12-week CGA
      correlated with TIMP scores. CONCLUSIONS: Poor ability to lift the head in prone
      and an inability to align the head with the trunk during the pull-to-sit task
      were associated with poorer future motor outcome scores. Kinematic measurements
      of head control in early infancy may serve as reliable objective quantitative
      markers of future motor impairment and neurodevelopmental outcome.

PMID- 25621435
TI  - A validated UPLC-MS/MS assay using negative ionization mode for high-throughput
      determination of pomalidomide in rat plasma.
AB  - In this study, a sensitive UPLC-MS/MS assay was developed and validated for high
      throughput determination of pomalidomide in rat plasma using celecoxib as an
      internal standard (IS). Liquid liquid extraction using dichloromethane was
      employed to extract pomalidomide and IS from 200MUL of plasma. Chromatographic
      separation was carried on Acquity BEHTM C18 column (50mm*2.1mm, 1.7MUm) using an
      isocratic mobile phase of acetonitrile: 10mM ammonium acetate (80:20, v/v), at a
      flow rate of 0.250mL/min. Both pomalidomide and IS were eluted at 0.66+/-0.03 and
      0.80+/-0.03min, respectively, with a total run time of 1.5min only. A triple
      quadruple tandem mass spectrometer using electrospray ionization in negative mode
      was employed for analyte detection. The precursor to product ion transitions of
      m/z 272.01->160.89 for pomalidomide and m/z 380.08->316.01 for IS were used to
      quantify them respectively, multiple reaction monitoring mode. The developed
      method was validated according to regulatory guideline for bioanalytical method
      validation. The linearity in plasma sample was achieved in the concentration
      range of 0.47-400ng/mL (r(2)>=0.997). The intra and inter-day precision values
      were <=11.1% (RSD, %) whereas accuracy values ranged from -6.8 to 8.5% (RE, %).
      In addition, other validation results were within the acceptance criteria and the
      method was successfully applied in a pharmacokinetic study of pomalidomide in
      rats. 

PMID- 25621434
TI  - Cumulative use of strong anticholinergics and incident dementia: a prospective
      cohort study.
AB  - IMPORTANCE: Many medications have anticholinergic effects. In general,
      anticholinergic-induced cognitive impairment is considered reversible on
      discontinuation of anticholinergic therapy. However, a few studies suggest that
      anticholinergics may be associated with an increased risk for dementia.
      OBJECTIVE: To examine whether cumulative anticholinergic use is associated with a
      higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      population-based cohort study using data from the Adult Changes in Thought study
      in Group Health, an integrated health care delivery system in Seattle,
      Washington. We included 3434 participants 65 years or older with no dementia at
      study entry. Initial recruitment occurred from 1994 through 1996 and from 2000
      through 2003. Beginning in 2004, continuous replacement for deaths occurred. All
      participants were followed up every 2 years. Data through September 30, 2012,
      were included in these analyses. EXPOSURES: Computerized pharmacy dispensing data
      were used to ascertain cumulative anticholinergic exposure, which was defined as
      the total standardized daily doses (TSDDs) dispensed in the past 10 years. The
      most recent 12 months of use was excluded to avoid use related to prodromal
      symptoms. Cumulative exposure was updated as participants were followed up over
      time. MAIN OUTCOMES AND MEASURES: Incident dementia and Alzheimer disease using
      standard diagnostic criteria. Statistical analysis used Cox proportional hazards
      regression models adjusted for demographic characteristics, health behaviors, and
      health status, including comorbidities. RESULTS: The most common anticholinergic
      classes used were tricyclic antidepressants, first-generation antihistamines, and
      bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants
      (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A
      10-year cumulative dose-response relationship was observed for dementia and
      Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard
      ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI,
      0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365;
      1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96)
      for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer
      disease. Results were robust in secondary, sensitivity, and post hoc analyses.
      CONCLUSIONS AND RELEVANCE: Higher cumulative anticholinergic use is associated
      with an increased risk for dementia. Efforts to increase awareness among health
      care professionals and older adults about this potential medication-related risk
      are important to minimize anticholinergic use over time.

PMID- 25621436
TI  - Elimination of chromatographic and mass spectrometric problems in GC-MS analysis
      of Lavender essential oil by multivariate curve resolution techniques: Improving
      the peak purity assessment by variable size moving window-evolving factor
      analysis.
AB  - In analysis of complex natural matrices by gas chromatography-mass spectrometry
      (GC-MS), many disturbing factors such as baseline drift, spectral background,
      homoscedastic and heteroscedastic noise, peak shape deformation (non-Gaussian
      peaks), low S/N ratio and co-elution (overlapped and/or embedded peaks) lead the
      researchers to handle them to serve time, money and experimental efforts. This
      study aimed to improve the GC-MS analysis of complex natural matrices utilizing
      multivariate curve resolution (MCR) methods. In addition, to assess the peak
      purity of the two-dimensional data, a method called variable size moving window
      evolving factor analysis (VSMW-EFA) is introduced and examined. The proposed
      methodology was applied to the GC-MS analysis of Iranian Lavender essential oil,
      which resulted in extending the number of identified constituents from 56 to 143
      components. It was found that the most abundant constituents of the Iranian
      Lavender essential oil are alpha-pinene (16.51%), camphor (10.20%), 1,8-cineole
      (9.50%), bornyl acetate (8.11%) and camphene (6.50%). This indicates that the
      Iranian type Lavender contains a relatively high percentage of alpha-pinene.
      Comparison of different types of Lavender essential oils showed the composition
      similarity between Iranian and Italian (Sardinia Island) Lavenders. 

PMID- 25621437
TI  - Validation of an analytical method for nitrous oxide (N2O) laughing gas by
      headspace gas chromatography coupled to mass spectrometry (HS-GC-MS): forensic
      application to a lethal intoxication.
AB  - Drug abuse is a widespread problem affecting both teenagers and adults. Nitrous
      oxide is becoming increasingly popular as an inhalation drug, causing harmful
      neurological and hematological effects. Some gas chromatography-mass spectrometry
      (GC-MS) methods for nitrous oxide measurement have been previously described. The
      main drawbacks of these methods include a lack of sensitivity for forensic
      applications; including an inability to quantitatively determine the
      concentration of gas present. The following study provides a validated method
      using HS-GC-MS which incorporates hydrogen sulfide as a suitable internal
      standard allowing the quantification of nitrous oxide. Upon analysis, sample and
      internal standard have similar retention times and are eluted quickly from the
      molecular sieve 5A PLOT capillary column and the Porabond Q column therefore
      providing rapid data collection whilst preserving well defined peaks. After
      validation, the method has been applied to a real case of N2O intoxication
      indicating concentrations in a mono-intoxication. 

PMID- 25621438
TI  - Light-controlled spin filtering in bacteriorhodopsin.
AB  - The role of the electron spin in chemistry and biology has received much
      attention recently owing to to the possible electromagnetic field effects on
      living organisms and the prospect of using molecules in the emerging field of
      spintronics. Recently the chiral-induced spin selectivity effect was observed by
      electron transmission through organic molecules. In the present study, we
      demonstrated the ability to control the spin filtering of electrons by light
      transmitted through purple membranes containing bacteriorhodopsin (bR) and its
      D96N mutant. The spin-dependent electrochemical cyclic voltammetry (CV) and
      chronoamperometric measurements were performed with the membranes deposited on
      nickel substrates. High spin-dependent electron transmission through the
      membranes was observed; however, after the samples were illuminated by 532 nm
      light, the spin filtering in the D96N mutant was dramatically reduced whereas the
      light did not have any effect on the wild-type bR. Beyond demonstrating spin
      dependent electron transmission, this work also provides an interesting insight
      into the relationship between the structure of proteins and spin filtering by
      conducting electrons. 

PMID- 25621439
TI  - Fulfilling the vision of environmental public health tracking.

PMID- 25621440
TI  - Using tracking infrastructure to support public health programs, policies, and
      emergency response in New York City.
AB  - OBJECTIVE: To describe how the New York City (NYC) Tracking Program has used
      nationally mandated Secure Portal infrastructure and staff analytical expertise
      to support programs and inform policy. SETTING: The NYC Health Department
      assesses, investigates, and acts on a wide range of environmental concerns to
      protect the health of New Yorkers. DESIGN: Specific examples of highly effective
      policies or initiatives that relied on the NYC Tracking Program are described,
      including restaurant sanitary grade posting, rat indexing, converting boilers to
      cleaner-burning fuels, reducing exposure to mercury from fish and contaminated
      products, and responding to Superstorm Sandy. CONCLUSIONS: The NYC Tracking
      Program supports the Health Department in using inspectional, administrative, and
      health data to guide operations. Tracking has also allowed internal and external
      partners to use these data to guide policy development.

PMID- 25621441
TI  - Data to action: using environmental public health tracking to inform decision
      making.
AB  - CONTEXT: Public health surveillance includes dissemination of data and
      information to those who need it to take action to prevent or control disease.
      The concept of data to action is explicit in the mission of the Centers for
      Disease Control and Prevention's (CDC's) National Environmental Public Health
      Tracking Program (Tracking Program). The CDC has built a National Environmental
      Public Health Tracking Network (Tracking Network) to integrate health and
      environmental data to drive public health action (PHA) to improve communities'
      health. OBJECTIVE: To assess the utility of the Tracking Program and Tracking
      Network in environmental public health practice and policy making. DESIGN: We
      analyzed information on how Tracking (all program components hereafter referred
      to generally as "Tracking") has been used to drive PHAs within funded states and
      cities (grantees). Two case studies are presented to highlight Tracking's
      utility. SETTING: Analyses included all grantees funded between 2005 and 2013.
      PARTICIPANTS: Twenty-seven states, 3 cities, and the District of Columbia ever
      received funding. MAIN OUTCOME MEASURES: We categorized each PHA reported to
      determine how grantees became involved, their role, the problems addressed, and
      the overall action. RESULTS: Tracking grantees reported 178 PHAs from 2006 to
      2013. The most common overall action was "provided information in response to
      concern" (n = 42), followed by "improved a public health program, intervention,
      or response plan" (n = 35). Tracking's role was most often either to enhance
      surveillance (24%) or to analyze data (23%). In 47% of PHAs, the underlying
      problem was a concern about possible elevated rates of a health outcome, a
      potential exposure, or a potential association between a hazard and a health
      outcome. PHAs were started by a request for assistance (48%), in response to an
      emergency (8%), and though routine work by Tracking programs (43%). CONCLUSION:
      Our review shows that the data, expertise, technical infrastructure, and other
      resources of the Tracking Program and Tracking Network are driving state and
      local PHAs.

PMID- 25621443
TI  - Multiple measures on the Environmental Public Health Tracking Network.
AB  - SETTING: The Centers for Disease Control and Prevention's National Environmental
      Public Health Tracking Program is leading an initiative to build a National
      Environmental Public Health Tracking Network (Tracking Network) that integrates
      data into a network of standardized electronic data to provide valid scientific
      information on environmental exposures and adverse health conditions, as well as
      spatial and temporal relations between them. The Web-based Tracking Network is
      designed for different audiences including government, the academic community,
      and the public. A primary goal of the Tracking Network is to allow the
      exploration of data on health effects, environments, and demographics. The wide
      variety of data types along with stratifications present a complex problem when
      developing system functionality to query and display disparate data
      simultaneously in a comparable way using charts, tables, and maps. OBJECTIVE:
      While the ability to query and display data that span across geographies and
      multiple time periods for a single type of data has been the main feature set of
      the Tracking Network, allowing the same for multiple data types is needed to
      enable users to explore trends and possible associations among health and
      environmental data. METHODS: As a first step, a multidisciplinary team was formed
      to address complex issues related to developing the ability to view multiple
      measures on the Tracking Network. The team then iterated through steps involving
      requirements gathering, the segmentation of the requirements into functional
      areas, submission of proposals to address those functional areas, and finally
      evaluation of the proposals to address functional areas. CONCLUSIONS: Adding the
      ability to view multiple measures is an important step to improve Tracking
      Network users' exploration of the environmental health status of their
      communities. With this capability, public health practitioners and other users
      can formulate hypotheses, analyze trends, and explore possible relationships
      across a wide variety of environmental and health information.

PMID- 25621442
TI  - A decade of environmental public health tracking (2002-2012): progress and
      challenges.
AB  - BACKGROUND: The creation of the Centers for Disease Control and Prevention
      Environmental Public Health Tracking Program spawned an invigorating and
      challenging approach toward implementing the nation's first population-based,
      environmental disease tracking surveillance system. More than 10 years have
      passed since its creation and an abundance of peer-reviewed articles have been
      published spanning a broad variety of public health topics related primarily to
      the goal of reducing diseases of environmental origin. OBJECTIVE: To evaluate
      peer-reviewed literature related to Environmental Public Health Tracking during
      2002-2012, recognize major milestones and challenges, and offer recommendations.
      DESIGN: A narrative overview was conducted using titles and abstracts of peer
      reviewed articles, key word searches, and science-based search engine databases.
      MAIN OUTCOMES: Eighty published articles related to "health tracking" were
      identified and categorized according to 4 crossed-central themes. The Science and
      Research theme accounted for the majority of published articles, followed by
      Policy and Practice, Collaborations Among Health and Environmental Programs, and
      Network Development. CONCLUSIONS: Overall, progress was reported in the areas of
      data linkage, data sharing, surveillance methods, and network development.
      Ongoing challenges included formulating better ways to establish the connections
      between health and the environment, such as using biomonitoring, public water
      systems, and private well water data. Recommendations for future efforts include
      use of data to inform policy and practice and use of electronic health records
      data for environmental health surveillance.

PMID- 25621444
TI  - Environmental public health tracking: driving environmental health information.
AB  - CONTEXT: Historically, public health professionals lacked the capacity to
      evaluate and conduct key investigations into the health of their environment. By
      bringing together environmental and health effects data from a variety of data
      sources, the National Environmental Public Health Tracking Network (Tracking)
      allows users to easily analyze and research the relationships between human
      health and the environment. OBJECTIVE: As the Tracking Network has matured, its
      information has been used to guide public health actions, generate hypothesis,
      and demonstrate relationships between environment and health outcomes.
      PARTICIPANTS: The Tracking Network is composed of state, local, and national
      environment and public health partners. SETTINGS: The Environmental Public Health
      Tracking Network is part of the National Center for Environmental Health at the
      Centers for Disease Control and Prevention. DESIGN: Tracking standardizes
      existing data from diverse sources while leveraging technologies and applying
      sound communication practices to provide a user-friendly interface for the data
      system by all types of users.

PMID- 25621445
TI  - Development of a Web-based tool to collect and display water system customer
      service areas for public health action.
AB  - CONTEXT: Significant illness is associated with biological contaminants in
      drinking water, but little is known about health effects from low levels of
      chemical contamination in drinking water. To examine these effects in
      epidemiological studies, the sources of drinking water of study populations need
      to be known. OBJECTIVE: The California Environmental Health Tracking Program
      developed an online application that would collect data on the geographic
      location of public water system (PWS) customer service areas in California, which
      then could be linked to demographic and drinking water quality data. DESIGN: We
      deployed the Water Boundary Tool (WBT), a Web-based geospatial crowdsourcing
      application that can manage customer service boundary data for each PWS in
      California and can track changes over time. We also conducted a needs assessment
      for expansion to other states. SETTING/PARTICIPANTS: The WBT was designed for
      water system operators, local and state regulatory agencies, and government
      entities. RESULTS: Since its public launch in 2012, the WBT has collected service
      area boundaries for about 2300 individual PWS, serving more than 90% of the
      California population. Results of the needs assessment suggest interest and
      utility for deploying such a tool among states lacking statewide PWS service area
      boundary data. CONCLUSIONS: Although the WBT data set is incomplete, it has
      already been used for a variety of applications, including fulfilling
      legislatively mandated reporting requirements and linking customer service areas
      to drinking water quality data to better understand local water quality issues.
      Development of this tool holds promise to assist with outbreak investigations and
      prevention, environmental health monitoring, and emergency preparedness and
      response.

PMID- 25621446
TI  - Developing a smartphone interface for the Florida Environmental Public Health
      Tracking Web portal.
AB  - As smartphone and tablet devices continue to proliferate, it is becoming
      increasingly important to tailor information delivery to the mobile device. The
      Florida Environmental Public Health Tracking Program recognized that the mobile
      device user needs Web content formatted to smaller screen sizes, simplified data
      displays, and reduced textual information. The Florida Environmental Public
      Health Tracking Program developed a smartphone-friendly version of the state Web
      portal for easier access by mobile device users. The resulting smartphone
      friendly portal combines calculated data measures such as inpatient
      hospitalizations and emergency department visits and presents them grouped by
      county, along with temporal trend graphs. An abbreviated version of the public
      health messaging provided on the traditional Web portal is also provided, along
      with social media connections. As a result of these efforts, the percentage of
      Web site visitors using an iPhone tripled in just 1 year. 

PMID- 25621447
TI  - Health outcomes associated with smoke exposure in Albuquerque, New Mexico, during
      the 2011 Wallow fire.
AB  - OBJECTIVE: This study examined the association between PM2.5 levels and emergency
      department (ED) visits for selected health outcomes in Albuquerque, New Mexico,
      during the Wallow fire of 2011. DESIGN: Measurements of 24-hour average
      concentrations of PM2.5 obtained from the City of Albuquerque were used to
      calculate wildfire smoke exposure in Albuquerque. Daily ED visits were collected
      by the New Mexico Department of Health from individual nonfederal licensed
      facilities in the Albuquerque area. Poisson regression was used to assess the
      relationship between ED visits for selected respiratory and cardiovascular
      conditions and varying levels of PM2.5 exposure. SETTING: Albuquerque, New
      Mexico. PARTICIPANTS: Patients visiting an ED for select conditions before,
      during, and after the wildfire. MAIN OUTCOME MEASURE: Relative increase in ED
      visits for selected conditions during the wildfire period. RESULTS: Analysis of
      PM2.5 exposure data and ED visits in Albuquerque before and during the Wallow
      fire indicated that compared with the period prior to the fire, there was an
      increased risk of ED visits for some respiratory and cardiovascular conditions
      during heavy smoke conditions, and risk varied by age and sex. The population of
      65+ years was especially at risk for increased ED visits. There was a
      significantly increased risk of ED visits among the 65+ population for asthma (RR
      [relative rate] = 1.73, 95% confidence interval [CI] = 1.03-2.93) and for
      diseases of the veins, lymphatic and circulatory system (RR = 1.56, 95% CI = 1.00
      2.43). For the age group of 20 to 64 years, there was a statistically significant
      increase in ED visits for diseases of pulmonary circulation (RR = 2.64, 95% CI =
      1.42-4.9) and for cerebrovascular disease (RR = 1.69, 95% CI = 1.03-2.77).
      CONCLUSIONS: High levels of PM2.5 exposure due to the Wallow fire were associated
      with increased ED visits for respiratory and cardiovascular conditions in
      Albuquerque. More effective and targeted preventive measures are necessary to
      reduce morbidity rates associated with wildfire smoke exposure among vulnerable
      populations.

PMID- 25621448
TI  - Maryland environmental public health tracking outreach with Spanish-speaking
      persons living in Baltimore city or county.
AB  - CONTEXT: The 2000 Pew reports became the impetus for the National Environmental
      Public Health Tracking (EPHT) Program, but there was no mention that Spanish
      speaking persons are at increased risk of exposure to environmental hazards.
      OBJECTIVE: To undertake successful EPHT outreach on Spanish-speaking persons
      (Hispanics), it is necessary to better understand their environmental health
      profile and barriers to health care access. DESIGN: Behavioral Risk Factor
      Surveillance System (BRFSS) survey questions were administered orally in Spanish
      to Spanish-speaking study participants. SETTING: Volunteers were tested at a non
      for-profit social service and referral agency in Baltimore. PARTICIPANTS: To
      control for acculturation, only Spanish-speaking persons who had lived in the
      United States for less than 10 years were selected. MAIN OUTCOME MEASURES:
      Responses to 40 BRFSS survey questions asked during the assessment and completion
      of 3 intervention activities. RESULTS: This study provides new information about
      Spanish-speaking persons, most of whom (85.3%) would not have been included in
      the landline administration of the BRFSS survey. Although 29.9% of the
      participants reported indoor pesticide use and another 9.2% reported outdoor
      pesticide use, lifetime (3.5%) and current (1.2%) asthma prevalence was
      significantly lower than asthma prevalence reported by Maryland Hispanics and all
      Maryland residents. There were significantly lower cholesterol screening (21.5%)
      and a significantly higher prevalence of diabetes (12.5%) in Spanish-speaking
      participants than in Maryland Hispanics and all Maryland residents. Among study
      participants, only 7.8% had health insurance and 39.9% reported that they could
      not see a doctor. Of the 3 outreach efforts completed, the most promising one
      involved asking Spanish-English-speaking health care professionals to distribute
      Spanish comic books about pesticides exposures and health outcomes in community
      settings where Spanish-only speakers and children were found. CONCLUSIONS: The
      effectiveness of passive and community-based EPHT interventions directed toward
      Spanish-only speakers has to be evaluated.

PMID- 25621449
TI  - Linking air pollution data and adverse birth outcomes: environmental public
      health tracking in New York State.
AB  - BACKGROUND: Studies investigating associations between ambient air pollution and
      fetal growth and gestational duration have reported inconclusive findings.
      OBJECTIVES: The study goal was to use the Environmental Public Health Tracking
      Network to describe the association between exposure to particulate matter
      (PM2.5) and ozone and term low birth weight (TLBW) in New York State. METHODS:
      Birth data for the years 2001-2006 were linked to Census data and hierarchical
      Bayesian modeled air pollution data. Daily 8-hour maximums for ozone and daily
      average PM2.5 estimates were averaged by trimester and exposure quartiles. The
      Environmental Public Health Tracking Academic Center for Excellence at Rutgers
      University partnered with New York and several other states to create a
      statistical program that uses logistic regression to determine the association
      between air pollution exposure and TLBW. RESULTS: There were no consistent dose
      response relationships between the pollutants and TLBW. Ozone exposure was
      associated with a higher risk of TLBW only in the first trimester, but these
      results were not statistically significant. Exposure to the third quartile of
      ozone for the full gestational period had negative associations with TLBW (odds
      ratio = 0.86; 95% confidence interval, 0.81-0.92). CONCLUSION: Collaboration
      within the Environmental Public Health Tracking Network to share methods and data
      for research proved feasible and efficient in assessing the relationship of air
      pollutants to adverse birth outcomes. This study finds little evidence to support
      positive associations between exposure to ozone or PM2.5 and TLBW in New York
      State.

PMID- 25621450
TI  - Using an environmental public health tracking biomonitoring study to validate
      safe water restoration efforts in Florida.
AB  - CONTEXT: Inorganic arsenic is a carcinogen when consumed over many years and is
      the type of arsenic that is associated with well water. Private wells in many
      central Florida counties have been found to contain levels of arsenic above 10
      MUg/L, which is the maximum contaminant level (MCL) established by the US
      Environmental Protection Agency. OBJECTIVE: The purpose of this study was to test
      whether individuals living in homes with arsenic levels above the MCL who use
      bottled water or have a point of use (POU) filter on their main source of water
      in the house (eg, kitchen sink) are ingesting unsafe levels of arsenic through
      other unfiltered water sources in the home. DESIGN: Case-control study of
      residents with private wells above (case) and below (control) the MCL for arsenic
      in drinking water (10 MUg/L) conducted between April and July 2013. SETTING AND
      PARTICIPANTS: Residents with private wells living in Hernando County, Florida,
      where nearly 400 unique wells of 1200 tested have been found to have elevated
      arsenic levels (targeted sampling). INTERVENTION: Participants with elevated
      water arsenic levels were referred to the Florida Safe Water Restoration Program
      for assistance in obtaining bottled water vouchers and/or POU filters. MAIN
      OUTCOME MEASURES: Creatinine-corrected total urinary arsenic levels and
      information on water use and consumption behaviors, dietary intake, and other
      possible exposure sources. RESULTS: Total urinary arsenic levels were similar for
      cases using POU filters or bottled water when compared with controls (geometric
      means of 7.17 and 7.19 MUg/L, respectively). CONCLUSIONS: The current practice
      used by the Florida Safe Water Restoration Program of supplying POU filters or
      bottled water to households with arsenic levels in private wells between 10 and
      50 MUg/L appears to be sufficient to protect residents from arsenic exposure
      through tap water.

PMID- 25621451
TI  - Using environmental public health tracking to identify community targets for
      public health actions in childhood lead poisoning in Wisconsin.
AB  - OBJECTIVE: In an effort to improve the ability of local public health departments
      to target resources to the highest need regions, the Wisconsin Environmental
      Public Health Tracking (WI EPHT) Program worked to enhance its public portal to
      benefit the Wisconsin Childhood Lead Poisoning Prevention Program (WCLPPP) and
      other programs. The WI EPHT Program conducted this enhancement in collaboration
      with WCLPPP. DESIGN/SETTING: The WI EPHT enhanced public portal is the next phase
      of Wisconsin's ongoing efforts in environmental public health tracking. As part
      of this process, this new mapping application includes mapping capacity that
      provides information on childhood lead testing and results at county and census
      tract levels in Wisconsin. METHODS: The WI EPHT Program will update its public
      portal to have the capability to map data at a subcounty level (ie, census tract
      or zip code) for some data topics when such data are available. RESULTS: This
      tool is available to local public health departments and other public health
      organizations throughout Wisconsin as a resource to identify communities most
      affected by the Centers for Disease Control and Prevention's new guidelines with
      regard to childhood lead poisoning. CONCLUSIONS: The collaboration between WI
      EPHT and WCLPPP on updating and enhancing the portal exemplifies the power of
      environmental health data to inform a more accurate understanding of public
      health problems.

PMID- 25621452
TI  - Private well water in Colorado: collaboration, data use, and public health
      outreach.
AB  - As a result of participating in the Centers for Disease Control and Prevention's
      Private Well Initiative and Environmental Public Health Tracking Network
      (Tracking), the Colorado Department of Public Health and Environment was able to
      inventory private well water quality data, prioritize potential health concerns
      associated with drinking water from these wells, and create a Web portal for
      sharing public health information regarding private well water. The Colorado
      Department of Public Health and Environment collaborated with a local health
      department to pilot the project prior to a public implementation. Approximately
      18 data sets were identified and inventoried. The Colorado Department of Public
      Health and Environment also participated in development and pilot testing of best
      practices for display of well water quality data with other Tracking states.
      Available data sets were compiled and summarized, and the data made available on
      the Colorado Tracking portal using geographic information system technology to
      support public health outreach regarding private wells. 

PMID- 25621453
TI  - Evaluation of available data sources to prioritize parishes for arsenic
      monitoring and outreach related to private well drinking water.
AB  - OBJECTIVE: The objective of this assessment was to identify and evaluate data
      sets for use in the surveillance of arsenic hazards and private well drinking
      water use in Louisiana. DESIGN: Features, strengths, and limitations of the data
      sets are described, and prioritization criteria are applied to identify areas in
      need of further monitoring or outreach. SETTING: Recent efforts have been made by
      the Environmental Public Health Tracking Network to evaluate the quality of
      private well water data for the purpose of supporting state and national
      surveillance activities. Like most states, Louisiana does not collect or mandate
      reporting of private well water quality data. Therefore, responding to public
      concerns about private well water quality requires an identification and
      evaluation of existing data. MAIN OUTCOME MEASURES: Data evaluated include
      measures of arsenic in groundwater and soil, private well water use, and
      biomonitoring results. RESULTS: The Environmental Protection Agency's Safe
      Drinking Water Information System and the US Geological Survey's Water Use data
      set were the most informative, nationally available data sets for conducting
      private well water arsenic surveillance. Three priority parishes were identified
      on the basis of a selection criteria, although all parishes require more private
      well sampling data. CONCLUSION: While the data reviewed enabled preliminary
      identification of parishes in need of monitoring and outreach, data limitations
      (particularly, a lack of statewide well water quality data) prevent a
      comprehensive evaluation of well water arsenic hazards and private well water
      use. A large number of unregistered wells further impede risk determination.
      Reliance on existing data sources is necessary, but development of metadata
      documentation is essential to prevent data misinterpretation. Increased outreach
      and policies to promote or mandate private well testing and reporting are needed
      to enable a comprehensive private well water tracking system.

PMID- 25621454
TI  - Determination of heavy metal ions in vegetable samples using a magnetic metal
      organic framework nanocomposite sorbent.
AB  - This paper describes the synthesis and application of a novel magnetic metal
      organic framework (MOF) [(Fe3O4-benzoyl isothiocyanate)/Cu3(benzene-1,3,5
      tricarboxylate)2] to pre-concentrate trace amounts of Cd(II), Pb(II), Zn(II) and
      Cr(III) ions and their determination by flame atomic absorption spectrometry. A
      Box-Behnken design was used to find the parameters affecting the pre
      concentration procedure through response surface methodology. Three factors
      including uptake time, amount of the magnetic sorbent and pH of the sample were
      selected as affecting factors in the sorption step, and four factors including
      type, volume and concentration of the eluent as well as the elution time were
      selected in the elution step for the optimisation study. The opted values were 30
      mg, 10.1 min, 5.9, EDTA, 4.0 ml, 0.57 mol l(-1) EDTA solution and 13.0 min for
      the amount of the magnetic sorbent, uptake time, pH of the sample, type, volume,
      concentration of the eluent, and elution time, respectively. The limits of
      detection (LODs) were 0.12, 0.7, 0.16, and 0.4 ng ml(-1) for Cd(II), Pb(II),
      Zn(II) and Cr(III) ions, respectively. The relative standard deviations (RSDs) of
      the method were less than 7.2% for five separate batch experiments for the
      determination of 30 MUg l(-1) of Cd(II), Pb(II), Zn(II) and Cr(III) ions. The
      sorption capacity of the [(Fe3O4-benzoyl isothiocyanate)/MOF] was 175 mg g(-1)
      for Cd(II), 168 mg g(-1) for Pb(II), 210 mg g(-1) for Zn(II) and 196 mg g(-1) for
      Cr(III). It was found that the magnetic MOF nanocomposite demonstrated a higher
      capacity compared with Fe3O4-benzoyl isothiocyanate. Finally, the magnetic MOF
      nanocomposite was successfully applied to the rapid extraction of trace amounts
      of the heavy metal ions from vegetable samples.

PMID- 25621455
TI  - Solar-driven proton and carbon dioxide reduction to fuels-lessons from
      metalloenzymes.
AB  - Metalloenzymes such as hydrogenases and carbon monoxide dehydrogenase can be
      attached to light-harvesting agents to produce informative photocatalytic systems
      of varying intricacy. Systematic studies yield important insight into mechanistic
      and design principles of artificial photosynthesis-one route to future renewable
      energy conversion, and the unconventional experiments reveal interesting new
      criteria for the catalytic performance of metals in biology. Recent advances are
      interpreted in terms of the importance of enzyme active centres that have evolved
      to perform fast and efficient catalysis using abundant elements, along with the
      ability of enzymes to trap photo-generated electrons by virtue of having
      receding, buried relay centres with low reorganisation energies.

PMID- 25621456
TI  - Oxygen-evolving complex of Photosystem II: an analysis of second-shell residues
      and hydrogen-bonding networks.
AB  - The oxygen-evolving complex (OEC) is a Mn4O5Ca cluster embedded in the
      Photosystem II (PSII) protein complex. As the site of water oxidation, the OEC is
      connected to the lumen by channels that conduct water, oxygen, and/or protons
      during the catalytic cycle. The hydrogen-bond networks found in these channels
      also serve to stabilize the oxidized intermediates, known as the S states. We
      review recent developments in characterizing these networks via protein
      mutations, molecular inhibitors, and computational modeling. On the basis of
      these results, we highlight regions of the PSII protein in which changes have
      indirect effects on the S1, S2, and S3 oxidation states of the OEC while still
      allowing photosynthetic activity. 

PMID- 25621458
TI  - Large multiallelic copy number variations in humans.
AB  - Thousands of genomic segments appear to be present in widely varying copy numbers
      in different human genomes. We developed ways to use increasingly abundant whole
      genome sequence data to identify the copy numbers, alleles and haplotypes present
      at most large multiallelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the
      1000 Genomes Project to identify most large (>5-kb) mCNVs, including 3,878
      duplications, of which 1,356 appear to have 3 or more segregating alleles. We
      find that mCNVs give rise to most human variation in gene dosage-seven times the
      combined contribution of deletions and biallelic duplications-and that this
      variation in gene dosage generates abundant variation in gene expression. We
      describe 'runaway duplication haplotypes' in which genes, including HPR and ORM1,
      have mutated to high copy number on specific haplotypes. We also describe
      partially successful initial strategies for analyzing mCNVs via imputation and
      provide an initial data resource to support such analyses. 

PMID- 25621457
TI  - Survival and morbidity of preterm children born at 22 through 34 weeks' gestation
      in France in 2011: results of the EPIPAGE-2 cohort study.
AB  - IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are
      needed for assessing perinatal care, informing parents, making decisions about
      care, and providing evidence for clinical guidelines. OBJECTIVES: To determine
      survival and neonatal morbidity of infants born from 22 through 34 completed
      weeks' gestation in France in 2011 and compare these outcomes with a comparable
      cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a
      national, prospective, population-based cohort study conducted in all maternity
      and neonatal units in France in 2011. A total of 2205 births (stillbirths and
      live births) and terminations of pregnancy at 22 through 26 weeks' gestation,
      3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort
      data were collected from January 1 through December 31, 1997, and from March 28
      through December 31, 2011. Analyses for 1997 were run for the entire year and
      then separately for April to December; the rates for survival and morbidities did
      not differ. Data are therefore presented for the whole year in 1997 and the 8
      month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to
      discharge and survival without any of the following adverse outcomes: grade III
      or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe
      bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or
      necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born
      before 24 weeks' gestation survived to discharge: 31.2% of those born at 24
      weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27
      through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home
      without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks,
      30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at
      32 through 34 weeks. Compared with 1997, the proportion of infants surviving
      without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29
      weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for
      those born at less than 25 weeks. The rates of antenatal corticosteroid use,
      induced preterm deliveries, cesarean deliveries, and surfactant use increased
      significantly in all gestational-age groups, except at 22 through 23 weeks.
      CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for
      newborns born at 25 through 31 weeks' gestation was accompanied by an important
      reduction in severe morbidity, but survival remained rare before 25 weeks.
      Although improvement in survival at extremely low gestational age may be
      possible, its effect on long-term outcomes requires further studies. The long
      term results of the EPIPAGE-2 study will be informative in this regard.

PMID- 25621459
TI  - Adaptation and possible ancient interspecies introgression in pigs identified by
      whole-genome sequencing.
AB  - Domestic pigs have evolved genetic adaptations to their local environmental
      conditions, such as cold and hot climates. We sequenced the genomes of 69 pigs
      from 15 geographically divergent locations in China and detected 41 million
      variants, of which 21 million were absent from the dbSNP database. In a genome
      wide scan, we identified a set of loci that likely have a role in regional
      adaptations to high- and low-latitude environments within China. Intriguingly, we
      found an exceptionally large (14-Mb) region with a low recombination rate on the
      X chromosome that appears to have two distinct haplotypes in the high- and low
      latitude populations, possibly underlying their adaptation to cold and hot
      environments, respectively. Surprisingly, the adaptive sweep in the high-latitude
      regions has acted on DNA that might have been introgressed from an extinct Sus
      species. Our findings provide new insights into the evolutionary history of pigs
      and the role of introgression in adaptation. 

PMID- 25621461
TI  - Facile electrochemical synthesis of titanium dioxide dendrites and their
      electrochemical properties.
AB  - Titanium dioxide (TiO2) dendrites were successfully prepared by a simple
      electrochemical deposition technique in acidic solution. The TiO2 dendrites
      showed outstanding electrochemical properties. 

PMID- 25621462
TI  - Management of syphilis in HIV-positive individuals.
AB  - Since the turn of the millennium a sustained outbreak of syphilis among men who
      have sex with men continues, approximately 20-50% of whom have concurrent HIV
      infection. In this paper we aim to explore the controversies that exist around
      the management of syphilis in HIV-positive individuals. Not only do HIV-positive
      people have different clinical manifestations of syphilis they have higher rates
      of asymptomatic neurological involvement, slower serological response to
      treatment and higher serological failure than HIV-negative individuals in most
      studies. Whether long-term clinical outcomes are different or affected by the
      antibiotic regimen selected remains to be established. The optimal antimicrobial
      regimen to treat syphilis in HIV is unknown due to a dearth of randomised
      controlled trial data. International guidelines state that the antibiotic
      management of syphilis is the same regardless of HIV status, with early syphilis
      treated with a single dose of benzathine penicillin G 2.4mU intrmuscularly. In
      practice, however, the majority of surveyed clinicians do treat HIV-positive
      people with more intensive antibiotics suggesting a lack of faith in guidelines.
      Factors which appear to affect the likelihood of developing neurological disease
      include CD4(+) count of <350 cells/MUL, absence of antiretroviral therapy, rapid
      plasma regain (RPR) or venereal diseases reference laboratory titre (VDRL) >1:32,
      late-latent disease or lack of response to standard antibiotic treatment. We
      recommend a low-threshold for offering antibiotic treatment effective against
      neurosyphilis in HIV-positive people with syphilis, especially if they exhibit
      any of the above factors. 

PMID- 25621460
TI  - Convergent evolution of the genomes of marine mammals.
AB  - Marine mammals from different mammalian orders share several phenotypic traits
      adapted to the aquatic environment and therefore represent a classic example of
      convergent evolution. To investigate convergent evolution at the genomic level,
      we sequenced and performed de novo assembly of the genomes of three species of
      marine mammals (the killer whale, walrus and manatee) from three mammalian orders
      that share independently evolved phenotypic adaptations to a marine existence.
      Our comparative genomic analyses found that convergent amino acid substitutions
      were widespread throughout the genome and that a subset of these substitutions
      were in genes evolving under positive selection and putatively associated with a
      marine phenotype. However, we found higher levels of convergent amino acid
      substitutions in a control set of terrestrial sister taxa to the marine mammals.
      Our results suggest that, whereas convergent molecular evolution is relatively
      common, adaptive molecular convergence linked to phenotypic convergence is
      comparatively rare. 

PMID- 25621463
TI  - Catalytic epoxidation by perrhenate through the formation of organic-phase
      supramolecular ion pairs.
AB  - Organic-phase supramolecular ion pair (SIP) host-guest assemblies of perrhenate
      anions (ReO4(-)) with ammonium amide receptor cations are reported. These
      compounds act as catalysts for the epoxidation of alkenes by aqueous hydrogen
      peroxide under biphasic conditions and can be recycled several times with no loss
      in activity. 

PMID- 25621464
TI  - Recurrent Thyroid Eye Disease.
AB  - PURPOSE: The natural history of thyroid eye disease follows a biphasic course
      featuring an initial active stage followed by a durable quiescent stage.
      Reactivation of thyroid eye disease is defined by recurrence of inflammatory
      signs and symptoms after a period of stability lasting at least 6 months. It is
      thought to be rare and is poorly studied. The goal of this study was to define
      the incidence and characteristics of recurrent thyroid eye disease. METHODS: A
      retrospective chart review of 415 visits of patients with thyroid eye disease was
      performed between 2006 and 2012. Recurrent cases were identified by subjective
      historical accounts of disease recurrence, review of prior orbital imaging, and
      photographic evidence. RESULTS: Among 415 cases of thyroid eye disease, 65 cases
      of recurrence (15.7%) were identified. Most cases of reactivation occurred within
      the first 10 years after the initial episode of thyroid eye disease. The mean age
      of patients at the first event was 42.2 years and 52.6 years at the second event.
      Eighteen patients had identifiable events that may have triggered disease
      recurrence. The recurrence rate was higher among patients that had been smokers
      during their first episode of thyroid eye disease (22%) compared with the
      nonsmokers (14.6%). CONCLUSIONS: Although uncommon, recurrence of thyroid eye
      disease does not appear to be as rare as previously believed. A better
      understanding of the natural history of thyroid eye disease is important as it
      impacts patient education and management.

PMID- 25621465
TI  - Long-Term Correlates of Objectively Measured Physical Activity and Sedentary Time
      in Norwegian Men and Women.
AB  - BACKGROUND: Sex, age, body mass index (BMI), perceived health and health behavior
      are correlates known to affect physical activity and sedentary time. However,
      studies have often been cross-sectional, and less is known about long-term
      correlates. Thus, the aims were to investigate 1) the associations between a set
      of characteristics (demographic, biological, psychological, and behavioral) and
      objectively measured physical activity and sedentary time at 13-year follow-up,
      and 2) the association between changes in these characteristics over time and
      physical activity and sedentary time. METHODS: Baseline characteristics were
      collected in 40-year-olds in 1996, and follow-up data on objectively measured
      physical activity and sedentary time were obtained in 2009 (n = 240). Data were
      analyzed by multiple linear regressions. RESULTS: Self-reported physical activity
      (P < .001) and improved perceived health (P = .046) were positively associated
      with moderate-to-vigorous physical activity (MVPA) whereas BMI (P = .034) and
      increased BMI (P = .014) were negatively associated with MVPA at follow-up. Women
      spent less time being sedentary than men (P = .019). Education (P < .001) was
      positively associated and improved perceived health (P = .010) was negatively
      associated with sedentary time at follow-up. CONCLUSIONS: MVPA and sedentary time
      at follow-up were associated with behavioral, biological and demographic
      correlates. However, the nature of our analyses prevents us from inferring
      causality.

PMID- 25621466
TI  - Chiral nanostructuring of multivalent macrocycles in solution and on surfaces.
AB  - We describe the design and synthesis of a novel functionality-rich, homochiral
      macrocycle, possessing the overall molecular D2 symmetry, in which multivalency
      is introduced into the covalent framework by means of four suitably positioned
      pyridine moieties. The macrocycle synthesis is carried out with functionalized,
      enantiopure 1,1'-binaphthyl synthons as the source of chirality by means of a
      room temperature esterification reaction as the cyclization procedure. Upon
      addition of Pd(2+), coordination of the pyridine moieties occurs both intra and
      intermolecularly, to afford chiral ordered mono and dimeric macrocycles or
      multimeric aggregates depending on the solvents and conditions used. The metal
      binding event takes place in combination with a significant macrocyclic
      conformational rearrangement detected by circular dichroism spectroscopy. When in
      combination with a third component (C60), the macrocycle-Pd(2+) hybrid undergoes
      surface-confined nanostructuring into chiral nanofibres. 

PMID- 25621467
TI  - Clinical trial data sharing: what do we do now?

PMID- 25621468
TI  - Applicability of adipose-derived stem cells in type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is a form of early onset diabetes mellitus
      characterized by the autoimmune destruction of insulin-producing cells (IPCs),
      resulting in hyperglycemia and abnormal glucose metabolism. There are currently
      no treatments available capable of completely curing the symptoms associated with
      the loss or functional defects of IPCs. Nonetheless, stem cell therapy has
      demonstrated considerable promise in the replacement of IPCs with
      immunomodulatory functions to overcome the defects caused by T1DM. Adipose
      derived stem cells (ADSCs) are particularly suitable for use in cell
      transplantation therapy, especially when seeking to avoid the ethical issues and
      tumorigenic complications commonly associated with embryos or induced pluripotent
      stem cells. Cell-based treatments have demonstrated therapeutic advantages and
      clinical applicability of ADSCs in T1DM, ensuring their suitability for
      transplantation therapy. This manuscript focuses on the benefits and possible
      mechanisms in a T1DM-relevant model and displays positive results from finished
      or ongoing human clinical trials. We also discuss and hypothesize potential
      methods to further enhance the therapeutic efficacy of these efforts, such as a
      humanized rodent model and gene therapies for IPC clusters, to meet the clinical
      applicability of the standard. 

PMID- 25621469
TI  - Tar heel footprints in health care: John Price, MPA.

PMID- 25621470
TI  - World peace, to be a millionaire, and hoop dreams: adolescent wishes on health
      screening surveys.
AB  - OBJECTIVE: This study sought to learn the wishes of young adolescents via an open
      ended survey question and to determine the association of these wishes with
      sociodemographic variables. METHODS: We performed a cross-sectional study of
      consecutive adolescents aged 11-14 years who had a well-child visit at a clinic
      with a diverse patient population, who completed a Guidelines for Adolescent
      Preventive Services (GAPS) previsit health questionnaire, and who answered the
      question, "If you could have three wishes come true, what would they be?"
      Responses to this question were double-coded according to thematic content and
      whether wishes were for self, others, or both. RESULTS: Among 96 respondents,
      wishes for others were listed more frequently by girls than by boys (54% versus
      31%; P = .02). Girls also had more family-oriented wish themes (27% versus 10%; P
      = .04). Boys were more likely to wish for success (17% versus 4%; P = .05). Among
      respondents with private insurance, 45% wished for the good for the world, with
      responses such as "world peace"; only 12% of respondents with Medicaid wished for
      the good of the world (P = .01). No statistically significant differences were
      identified by race/ethnicity or age. Positive future orientation themes such as
      career were not as prioritized as previously suggested in the literature.
      LIMITATIONS: The sample population derives from a single university-based clinic
      in North Carolina; while diverse, this population may not be representative of
      larger groups. CONCLUSIONS: Many wishes seemed predictable (ie, for wealth,
      athleticism), but occasionally wishes were poignant and original ("to have papers
      for my parents to pass the border"); this finding reinforces the value of
      listening to adolescents' wishes. Both sex and insurance status were related to
      wish themes. Further research should determine how knowledge of adolescents'
      wishes can be used to best direct individual care.

PMID- 25621471
TI  - Barriers to reporting child maltreatment: do emergency medical services
      professionals fully understand their role as mandatory reporters?
AB  - BACKGROUND: Child maltreatment is underreported in the United States and in North
      Carolina. In North Carolina and other states, mandatory reporting laws require
      various professionals to make reports, thereby helping to reduce underreporting
      of child maltreatment. This study aims to understand why emergency medical
      services (EMS) professionals may fail to report suspicions of maltreatment
      despite mandatory reporting policies. METHODS: A web-based, anonymous, voluntary
      survey of EMS professionals in North Carolina was used to assess knowledge of
      their agency's written protocols and potential reasons for underreporting
      suspicion of maltreatment (n=444). Results were based on descriptive statistics.
      Responses of line staff and leadership personnel were compared using chi-square
      analysis. RESULTS: Thirty-eight percent of respondents were unaware of their
      agency's written protocols regarding reporting of child maltreatment.
      Additionally, 25% of EMS professionals who knew of their agency's protocol
      incorrectly believed that the report should be filed by someone other than the
      person with firsthand knowledge of the suspected maltreatment. Leadership
      personnel generally understood reporting requirements better than did line staff.
      Respondents indicated that peers may fail to report maltreatment for several
      reasons: they believe another authority would file the report, including the
      hospital (52.3%) or law enforcement (27.7%); they are uncertain whether they had
      witnessed abuse (47.7%); and they are uncertain about what should be reported
      (41.4%). LIMITATIONS: This survey may not generalize to all EMS professionals in
      North Carolina. CONCLUSIONS: Training opportunities for EMS professionals that
      address proper identification and reporting of child maltreatment, as well as
      cross-agency information sharing, are warranted.

PMID- 25621472
TI  - "Going down to the country".

PMID- 25621473
TI  - Rural health care: redefining access.
AB  - The population and demographics of rural America are shifting once again. As our
      nation's unprecedented health care reform unfolds, it is becoming clear that
      rural communities have unique strengths, and capitalizing on these strengths can
      position them well for this health care transformation. Equally important are the
      distinct challenges that--with careful planning, attention, and resources--can be
      transformed into opportunities to thrive in the new health care environment. The
      North Carolina Institute of Medicine's Task Force on Rural Health recently
      published a report that highlights the strengths and challenges of rural
      communities [1]. In order to fully leverage these opportunities, we must continue
      to acknowledge the fundamental importance of access to basic health care, while
      also broadening our discussion to collectively tackle the additional components
      necessary to create healthy, thriving rural communities. As we reexamine the
      needs of rural communities, we should broaden our discussions to include an
      expansion of the types of access that are necessary for strengthening rural
      health. Collaboration, successful recruitment and retention, availability of
      specialty services, quality care, and cost effectiveness are some of the issues
      that must come into discussions about access to services. With this in mind, this
      issue of the NCMJ explores opportunities to strengthen the health of North
      Carolina's rural communities. 

PMID- 25621474
TI  - Providing whole-person care: integrating behavioral health into primary care.
AB  - Integrated primary care in a patient-centered medical home is the best way to
      invite patients to engage in better self-care, to move from provider-based care
      to team-based care, and to address whole-person needs. However, primary care
      whether rural or urban, public or private-cannot become the default mental health
      system for North Carolinians with severe mental illness. 

PMID- 25621475
TI  - Telebehavioral health: clinical applications, benefits, technology needs, and
      setup.

PMID- 25621476
TI  - Finding and keeping health care providers in rural communities: culture change in
      recruitment at rural health group.
AB  - Transforming rural primary care is possible only when leadership is committed to
      a core set of competencies. Northeastern North Carolina, not always seen as an
      attractive locale for health professionals, has been developing a primary care
      medical home that emphasizes team-based care built upon respect, trust, and
      professionalism. 

PMID- 25621477
TI  - Physicians providing leadership for rural communities.

PMID- 25621478
TI  - Twenty-five years of serving the health care needs of rural North Carolina.
AB  - The Community Practitioner Program seeks to improve access to quality health care
      for North Carolina's most vulnerable people by providing educational loan
      repayment grants to primary care physicians, physician assistants, and nurse
      practitioners in return for their service in rural and underserved communities. 

PMID- 25621479
TI  - Financially fragile rural hospitals: mergers and closures.
AB  - Rural hospitals serve as major sources of health care and employment for their
      communities, but recently they have been under increased financial stress. What
      are the causes of this stress, and how have hospitals and their communities
      responded? 

PMID- 25621480
TI  - Rural hospitals face many challenges in transitioning to value-based care.

PMID- 25621481
TI  - Down east partnership for children is committed to launching healthy learners.
AB  - Down East Partnership for Children is committed to launching every child in Nash
      and Edgecombe counties as a healthy, lifelong learner by the end of the 3rd
      grade. Our 20-year journey has leveraged various resources and brought together
      education and health to make the greatest impact on economic success. 

PMID- 25621482
TI  - Building capacity to improve economic health.
AB  - The economic health of a community is vitally important for attracting and
      retaining businesses and for creating an environment in which people want to
      live, work, and play. Rural communities in North Carolina rely on a variety of
      partners and programs to build local capacity for job creation and the
      development of quality-of-life amenities. 

PMID- 25621483
TI  - The importance of health insurance and the safety net in rural communities.
AB  - Access to health insurance and health care are critical for people living in
      rural communities, where the safety net is fragile. However, rural communities
      face challenges as they enroll uninsured people in the health insurance
      marketplace, educate newly insured individuals on how to use insurance, and
      coordinate care for those who remain uninsured. 

PMID- 25621484
TI  - Connecting people to the source of their food: changing the way we think about
      food to improve health.
AB  - Whether it is linking farmers with buyers or teaching children about vegetables
      growing in a school garden, connecting people to the source of their food is a
      vital part of building rural food systems that are healthy food systems. 

PMID- 25621485
TI  - Healthy places NC.

PMID- 25621486
TI  - Medically necessary sterilization of a minor with intellectual disability: a case
      report and historical perspective.
AB  - Medical necessity may lead to secondary sterilization of individuals with
      intellectual disabilities, but legal statutes mandate that certain procedures be
      followed in these cases. In this article, we present a case of medically
      necessary sterilization of an individual with intellectual disability, and we
      discuss important legal statutes that guide this practice in North Carolina. 

PMID- 25621487
TI  - It's A-bout Time: Detailed Patterns of Physical Activity in Obese Adolescents
      Participating in a Lifestyle Intervention.
AB  - BACKGROUND: The detailed patterns of physical activity and sedentary behaviors of
      overweight and obese adolescents are unknown, but may be important for health
      outcomes and targeted intervention design. METHODS: Participants completed Curtin
      University's Activity, Food and Attitudes Program (CAFAP), an 8-week intervention
      with 12 months of maintenance intervention. Physical activity and sedentary time
      were assessed at 6 time periods with accelerometers and were analyzed by 1) time
      and type of day, 2) intensity bout patterns using exposure variation analysis,
      and 3) individual case analysis. RESULTS: Participants (n = 56) spent a lower
      percentage of time at baseline in light activity during school days compared with
      weekend days (24.4% vs 29.0%, P = .004). The majority of time was in long
      uninterrupted sedentary bouts of greater than 30 minutes (26.7% of total time,
      36.8% of sedentary time at baseline). Moderate activity was accumulated in short
      bouts of less than 5 minutes (3.1% of total time, 76.0% moderate time). Changes
      varied by individuals. CONCLUSIONS: Exposure variation analysis revealed specific
      changes in activity patterns in overweight and obese adolescents who participated
      in a lifestyle intervention. A better understanding of these patterns can help to
      design interventions that meaningfully affect specific behaviors, with unique
      health consequences.

PMID- 25621488
TI  - Immediate effects of an elastic knee sleeve on frontal plane gait biomechanics in
      knee osteoarthritis.
AB  - INTRODUCTION: Osteoarthritis of the knee affects millions of people. Elastic knee
      sleeves aim at relieving symptoms. While symptomatic improvements have been
      demonstrated as a consequence of elastic knee sleeves, evidence for biomechanical
      alterations only exists for the sagittal plane. We therefore asked what effect an
      elastic knee sleeve would have on frontal plane gait biomechanics. METHODS: 18
      subjects (8 women, 10 men) with osteoarthritis of the medial tibiofemoral joint
      walked over ground with and without an elastic knee sleeve. Kinematics and forces
      were recorded and joint moments were calculated using an inverse dynamics
      approach. Conditions with sleeve and without sleeve were compared with paired t
      Tests. RESULTS: With the sleeve, knee adduction angle at ground contact was
      reduced by 1.9 +/- 2.1 degrees  (P = 0.006). Peak knee adduction was reduced by
      1.5 +/- 1.6 degrees  (P = 0.004). The first peak knee adduction moment and
      positive knee adduction impulse were decreased by 10.1% (0.74 +/- 0.9 Nm * kg-1;
      P = 0.002) and 12.9% (0.28 +/- 0.3 Nm * s * kg-1; P < 0.004), respectively.
      CONCLUSION: Our study provides evidence that wearing an elastic knee sleeve
      during walking can reduce knee adduction angles, moments and impulse in subjects
      with knee osteoarthritis. As a higher knee adduction moment has previously been
      identified as a risk factor for disease progression in patients with medial knee
      osteoarthritis, we speculate that wearing a knee sleeve may be beneficial for
      this specific subgroup.

PMID- 25621489
TI  - Metro maps of plant disease dynamics--automated mining of differences using
      hyperspectral images.
AB  - Understanding the response dynamics of plants to biotic stress is essential to
      improve management practices and breeding strategies of crops and thus to proceed
      towards a more sustainable agriculture in the coming decades. In this context,
      hyperspectral imaging offers a particularly promising approach since it provides
      non-destructive measurements of plants correlated with internal structure and
      biochemical compounds. In this paper, we present a cascade of data mining
      techniques for fast and reliable data-driven sketching of complex hyperspectral
      dynamics in plant science and plant phenotyping. To achieve this, we build on top
      of a recent linear time matrix factorization technique, called Simplex Volume
      Maximization, in order to automatically discover archetypal hyperspectral
      signatures that are characteristic for particular diseases. The methods were
      applied on a data set of barley leaves (Hordeum vulgare) diseased with foliar
      plant pathogens Pyrenophora teres, Puccinia hordei and Blumeria graminis hordei.
      Towards more intuitive visualizations of plant disease dynamics, we use the
      archetypal signatures to create structured summaries that are inspired by metro
      maps, i.e. schematic diagrams of public transport networks. Metro maps of plant
      disease dynamics produced on several real-world data sets conform to plant
      physiological knowledge and explicitly illustrate the interaction between
      diseases and plants. Most importantly, they provide an abstract and interpretable
      view on plant disease progression. 

PMID- 25621490
TI  - The role of IL-23/Th17 pathway in patients with primary immune thrombocytopenia.
AB  - BACKGROUND: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding
      disorder with an unclear etiology. This study aims to investigate the role of IL
      23/Th17 pathway in patients with ITP. METHOD: The gene expressions of IL-17, IL
      23 and their receptors in ITP patients and healthy controls were analyzed by
      quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in
      plasma. Flow cytometry was used to detect the frequency of Th17 cells. The
      correlation between plasma IL-23 and IL-17 levels, Th17 cells, platelets were
      analyzed. The level of Th17-related cytokines was measured by ELISA following
      stimulation with IL-23. Subsequently, the IL-23 and IL-17 levels were measured in
      patients post-treatment. RESULTS: The PBMCs of ITP patients showed increased mRNA
      expression levels in each of the following: IL-23p19, IL-12p40, IL-23R, IL
      12Rbeta1, IL-17A, IL-17F, and RORC. In addition, elevated Th17 cells and plasma
      IL-17, IL-23 levels were also observed in these ITP patients. Furthermore, it was
      found that IL-23 levels in plasma are positively correlated with IL-17 levels and
      Th17 cells, yet negatively correlated with platelet count. Following IL-23
      stimulation in vitro, IL-17 levels showed significant elevation. Furthermore,
      both IL-23 and IL-17 levels decreased after effective treatment. CONCLUSION: The
      IL-23/Th17 pathway may be involved in the pathogenesis of ITP through enhancement
      of the Th17 response. Moreover, our results suggest that the IL-23/Th17 pathway
      is a potential therapeutic target in future attempts of ITP treatment.

PMID- 25621492
TI  - Sociosexual behaviors of male rats (Rattus norvegicus) in a seminatural
      environment.
AB  - Groups of rats (3 males and 4 cycling females) were housed in a seminatural
      environment consisting of a burrow and a large open area for a period of 8 days.
      Sociosexual interactions were recorded whenever 1 or several females were in
      behavioral estrus. Male sociosexual behaviors occurred in bouts (periods of
      sexual activity followed by more than 60 min without any sexual behavior), which
      could be ended either by mount (mean +/- 95% confidence interval was 38 +/- 13%
      of all bouts), intromission (21 +/- 15%), or ejaculation (40 +/- 18%). Bouts had
      a median duration of 2.8 +/- 0.9 h. Within a bout, the intensity of sexual
      behavior remained quite stable. Interestingly, there was no decline as the end of
      the bout approached. There was no relationship between the last event in the
      preceding bout and the interbout interval. Regardless of whether there was single
      or multiple females in estrus, the males copulated with all available females in
      an order that was not significantly different from random. Social behaviors like
      sniffing and anogenital sniffing were more frequent in the burrow whereas sexual
      interactions were more frequent in the open area. The seminatural environment
      employed here offers a considerable amount of information concerning sexual
      interactions that cannot be obtained in traditional pair tests. Whenever
      speculations about the biological function or adaptive value of sexual behaviors
      are to be made, it appears that the present approach is indicated.

PMID- 25621491
TI  - On the subjective acceptance during cardiovascular magnetic resonance imaging at
      7.0 Tesla.
AB  - PURPOSE: This study examines the subjective acceptance during UHF-CMR in a cohort
      of healthy volunteers who underwent a cardiac MR examination at 7.0T. METHODS:
      Within a period of two-and-a-half years (January 2012 to June 2014) a total of
      165 healthy volunteers (41 female, 124 male) without any known history of cardiac
      disease underwent UHF-CMR. For the assessment of the subjective acceptance a
      questionnaire was used to examine the participants experience prior, during and
      after the UHF-CMR examination. For this purpose, subjects were asked to respond
      to the questionnaire in an exit interview held immediately after the completion
      of the UHF-CMR examination under supervision of a study nurse to ensure accurate
      understanding of the questions. All questions were answered with "yes" or "no"
      including space for additional comments. RESULTS: Transient muscular contraction
      was documented in 12.7% of the questionnaires. Muscular contraction was reported
      to occur only during periods of scanning with the magnetic field gradients being
      rapidly switched. Dizziness during the study was reported by 12.7% of the
      subjects. Taste of metal was reported by 10.1% of the study population. Light
      flashes were reported by 3.6% of the entire cohort. 13% of the subjects reported
      side effects/observations which were not explicitly listed in the questionnaire
      but covered by the question about other side effects. No severe side effects as
      vomiting or syncope after scanning occurred. No increase in heart rate was
      observed during the UHF-CMR exam versus the baseline clinical examination.
      CONCLUSIONS: This study adds to the literature by detailing the subjective
      acceptance of cardiovascular magnetic resonance imaging examinations at a
      magnetic field strength of 7.0T. Cardiac MR examinations at 7.0T are well
      tolerated by healthy subjects. Broader observational and multi-center studies
      including patient cohorts with cardiac diseases are required to gain further
      insights into the subjective acceptance of UHF-CMR examinations.

PMID- 25621493
TI  - Critical psychology: A geography of intellectual engagement and resistance.
AB  - Critical psychology has become a generative and international movement in the
      last 5 decades, with self-identifying critical psychologists emerging from around
      the globe with publications and contributions, both theoretical and practical, in
      many areas of psychology. This article provides an overview of current trends in
      critical psychology and elucidates historical sources and theoretical tenets.
      Presented are the relationship between individual subjectivity and society, the
      role of power in the discipline, the problem of subjectification, the importance
      of reflexivity and intersubjectivity in the context of research practices,
      methodologies of change for different contexts, and the ethical-political
      positions from which critical psychologists operate. Challenges to critical
      psychology, which include engagements with indigenous psychologies, new forms of
      internationalization, and advancing transdisciplinary work, are discussed.

PMID- 25621494
TI  - Treatment of aromatase (CYP19A1) inhibitor reduces fertility in porcine sperm.
AB  - To ascertain whether aromatase (CYP19A1) expression is linked to sperm fertility
      of pigs, the present study determined the expression of the CYP19A1 gene in
      porcine sperm and its relationship with fertilization in vitro. First, to
      investigate its role in fertility, the presence of CYP19A1 of mRNA and protein
      expression in porcine sperm were confirmed by real-time (RT) or quantitative
      polymerase chain reaction (q-PCR) and by western blots. The expression levels
      were determined quantitatively using two sperm groups recovered by a Percoll
      gradient, which revealed that the sperm group with a low density had a higher
      penetration rate than that of the high-density group (P < 0.05). However, the
      expression level of CYP19A1 was not significantly different between the two
      groups. Secondly, to examine the effect of aromatase activity on fertilization,
      fresh semen was treated with a steroidal inhibitor, exemestane (50 MUM for 0.5
      h), followed by the dose- and time-dependent viability test. Our results clearly
      showed that an exemestane treatment effect (P < 0.05) was found for both the
      sperm-penetration rate and the oocyte cleavage rate. These results indicated that
      CYP19A1 could be involved in sperm fertility and its expression in sperm plays an
      important role in fertilization. 

PMID- 25621495
TI  - CRK proteins selectively regulate T cell migration into inflamed tissues.
AB  - Effector T cell migration into inflamed sites greatly exacerbates tissue
      destruction and disease severity in inflammatory diseases, including graft-versus
      host disease (GVHD). T cell migration into such sites depends heavily on
      regulated adhesion and migration, but the signaling pathways that coordinate
      these functions downstream of chemokine receptors are largely unknown. Using
      conditional knockout mice, we found that T cells lacking the adaptor proteins CRK
      and CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis, and
      diapedesis. Moreover, these two closely related proteins exhibited substantial
      functional redundancy, as ectopic expression of either protein rescued defects in
      T cells lacking both CRK and CRKL. We determined that CRK proteins coordinate
      with the RAP guanine nucleotide exchange factor C3G and the adhesion docking
      molecule CASL to activate the integrin regulatory GTPase RAP1. CRK proteins were
      required for effector T cell trafficking into sites of inflammation, but not for
      migration to lymphoid organs. In a murine bone marrow transplantation model, the
      differential migration of CRK/CRKL-deficient T cells resulted in efficient graft
      versus-leukemia responses with minimal GVHD. Together, the results from our
      studies show that CRK family proteins selectively regulate T cell adhesion and
      migration at effector sites and suggest that these proteins have potential as
      therapeutic targets for preventing GVHD. 

PMID- 25621496
TI  - Recombinant human CD19L-sTRAIL effectively targets B cell precursor acute
      lymphoblastic leukemia.
AB  - Patients with B cell precursor acute lymphoblastic leukemia (BPL) respond well to
      chemotherapy at initial diagnosis; however, therapeutic options are limited for
      individuals with BPL who relapse. Almost all BPL cells express CD19, and we
      recently cloned the gene encoding a natural ligand of the human CD19 receptor
      (CD19L). We hypothesized that fusion of CD19L to the soluble extracellular domain
      of proapoptotic TNF-related apoptosis-inducing ligand (sTRAIL) would markedly
      enhance the potency of sTRAIL and specifically induce BPL cell apoptosis due to
      membrane anchoring of sTRAIL and simultaneous activation of the CD19 and TRAIL
      receptor (TRAIL-R) apoptosis signaling pathways. Here, we demonstrate that
      recombinant human CD19L-sTRAIL was substantially more potent than sTRAIL and
      induced apoptosis in primary leukemia cells taken directly from BPL patients.
      CD19L-sTRAIL effectively targeted and eliminated in vivo clonogenic BPL xenograft
      cells, even at femtomolar-picomolar concentrations. In mice, CD19L-sTRAIL
      exhibited a more favorable pharmacokinetic (PK) profile than sTRAIL and was
      nontoxic at doses ranging from 32 fmol/kg to 3.2 pmol/kg. CD19L-sTRAIL showed
      potent in vivo antileukemic activity in NOD/SCID mouse xenograft models of
      relapsed and chemotherapy-resistant BPL at nontoxic fmol/kg dose levels.
      Together, these results suggest that recombinant human CD19L-sTRAIL has clinical
      potential as a biotherapeutic agent against BPL. 

PMID- 25621497
TI  - Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver
      disease.
AB  - Polyploidization is one of the most dramatic changes that can occur in the
      genome. In the liver, physiological polyploidization events occur during both
      liver development and throughout adult life. Here, we determined that a
      pathological polyploidization takes place in nonalcoholic fatty liver disease
      (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk
      factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the
      parenchyma of fatty livers displayed alterations of the polyploidization process,
      including the presence of a large proportion of highly polyploid mononuclear
      cells, which are rarely observed in normal hepatic parenchyma. Biopsies from
      patients with nonalcoholic steatohepatitis (NASH) revealed the presence of
      alterations in hepatocyte ploidy compared with tissue from control individuals.
      Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of
      the cell cycle was inefficient. This alteration was associated with activation of
      a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1
      complex. Furthermore, we determined that oxidative stress promotes the appearance
      of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed
      normal cell division and returned to a physiological state of polyploidy.
      Collectively, these findings indicate that oxidative stress promotes pathological
      polyploidization and suggest that this is an early event in NAFLD that may
      contribute to HCC development. 

PMID- 25621500
TI  - Long-term effect of latanoprost on central corneal thickness in normal-tension
      glaucoma: five-year follow-up results.
AB  - PURPOSE: To evaluate the long-term effect of latanoprost on central corneal
      thickness (CCT) in patients with normal-tension glaucoma (NTG). METHODS: This
      retrospective study included 41 eyes of 41 NTG patients and 40 eyes of 40
      individuals with glaucoma suspect (controls). Newly diagnosed NTG patients with
      no previous glaucoma treatment were administered latanoprost 0.005% monotherapy
      once a day. CCTs were measured by ultrasound pachymetry before treatment and
      followed up annually for 5 years. RESULTS: A significant reduction in mean CCT
      was observed in the NTG group [542.3+/-36.2 MUm vs. 533.7+/-32.9 MUm (n=41),
      P<0.001], but not in the control group [547.4+/-24.7 MUm vs. 546.8+/-25.0 MUm
      (n=40), P=0.59] at 5-year follow-up. In the NTG group, the CCT reduction mainly
      occurred during the first year of treatment (542.3+/-36.2 MUm vs. 536.9+/-32.8
      MUm, P=0.001), and no significant correlation was found between CCT and
      intraocular pressure reductions (r=0.16, P=0.32). CONCLUSIONS: Latanoprost
      significantly reduced CCT in NTG patients after 5 years of treatment. Serial
      observations of CCT might be helpful for the proper interpretation of glaucoma
      status in NTG patients.

PMID- 25621498
TI  - Evaluation of noncytotoxic DNMT1-depleting therapy in patients with
      myelodysplastic syndromes.
AB  - BACKGROUND: Mutational inactivation in cancer of key apoptotic pathway
      components, such as TP53/p53, undermines cytotoxic therapies that aim to increase
      apoptosis. Accordingly, TP53 mutations are reproducibly associated with poor
      treatment outcomes. Moreover, cytotoxic treatments destroy normal stem cells with
      intact p53 systems, a problem especially for myeloid neoplasms, as these cells
      reverse the low blood counts that cause morbidity and death. Preclinical studies
      suggest that noncytotoxic concentrations of the DNA methyltransferase 1 (DNMT1)
      inhibitor decitabine produce p53-independent cell-cycle exits by reversing
      aberrant epigenetic repression of proliferation-terminating (MYC-antagonizing)
      differentiation genes in cancer cells. METHODS: In this clinical trial, patients
      with myelodysplastic syndrome (n=25) received reduced decitabine dosages (0.1-0.2
      mg/kg/day compared with the FDA-approved 20-45 mg/m2/day dosage, a 75%-90%
      reduction) to avoid cytotoxicity. These well-tolerated doses were frequently
      administered 1-3 days per week, instead of pulse cycled for 3 to 5 days over a 4-
      to 6-week period, to increase the probability that cancer S-phase entries would
      coincide with drug exposure, which is required for S-phase-dependent DNMT1
      depletion. RESULTS: The median subject age was 73 years (range, 46-85 years), 9
      subjects had relapsed disease or were refractory to 5-azacytidine and/or
      lenalidomide, and 3 had received intensive chemoradiation to treat other cancers.
      Adverse events were related to neutropenia present at baseline: neutropenic fever
      (13 of 25 subjects) and septic death (1 of 25 subjects). Blood count improvements
      meeting the International Working Group criteria for response occurred in 11 of
      25 (44%) subjects and were highly durable. Treatment-induced freedom from
      transfusion lasted a median of 1,025 days (range, 186-1,152 days; 3 ongoing), and
      20% of subjects were treated for more than 3 years. Mutations and/or deletions of
      key apoptosis genes were frequent (present in 55% of responders and in 36% of
      nonresponders). Noncytotoxic DNMT1 depletion was confirmed by serial BM gamma
      H2AX (DNA repair/damage marker) and DNMT1 analyses. MYC master oncoprotein levels
      were markedly decreased. CONCLUSION: Decitabine regimens can be redesigned to
      minimize cytotoxicity and increase exposure time for DNMT1 depletion, to safely
      and effectively circumvent mutational apoptotic defects. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01165996. FUNDING: NIH (R01CA138858, CA043703); Department
      of Defense (PR081404); Clinical and Translational Science Award (CTSA)
      (UL1RR024989); and the Leukemia and Lymphoma Society (Translational Research
      Program).

PMID- 25621501
TI  - In situ synthesis of self-assembled three-dimensional graphene-magnetic palladium
      nanohybrids with dual-enzyme activity through one-pot strategy and its
      application in glucose probe.
AB  - The self-assembled three-dimensional graphene nanohybrids with in situ-formed
      Fe3O4 and Pd nanoparticles on it (3DRGO_Fe3O4-Pd) are first synthesized by the
      one-pot solvothermal method, which have intrinsic peroxidase-like and oxidase
      like activity. The catalytic mechanism is analyzed by the electron spin resonance
      (ESR), fluorescence, and electrochemical methods. The mimic enzyme catalytic
      activity of 3DRGO_Fe3O4-Pd is much higher than those of monometallic loaded
      nanohybrids and their physical mixture, probably caused by synergistic effect
      between Pd and Fe3O4 nanoparticles. The 3DRGO_Fe3O4-Pd nanohybrids was
      reproducible, stable, and reusable. After 10 cycles, the catalytic activity was
      still higher than 90%, and the morphology and structure were basically unchanged.
      Based on its high peroxidase-like activity, especially the enhanced affinity
      toward H2O2, a new colorimetric detection method for reduced glutathione (GSH)
      and glucose has been designed using H2O2 as an intermediary, which provides a
      simple, sensitive, and selective way to detect urine glucose of diabetes with a
      wide linear range and low detection limit. 

PMID- 25621499
TI  - Pluripotent stem cells reveal erythroid-specific activities of the GATA1 N
      terminus.
AB  - Germline GATA1 mutations that result in the production of an amino-truncated
      protein termed GATA1s (where s indicates short) cause congenital hypoplastic
      anemia. In patients with trisomy 21, similar somatic GATA1s-producing mutations
      promote transient myeloproliferative disease and acute megakaryoblastic leukemia.
      Here, we demonstrate that induced pluripotent stem cells (iPSCs) from patients
      with GATA1-truncating mutations exhibit impaired erythroid potential, but
      enhanced megakaryopoiesis and myelopoiesis, recapitulating the major phenotypes
      of the associated diseases. Similarly, in developmentally arrested GATA1
      deficient murine megakaryocyte-erythroid progenitors derived from murine
      embryonic stem cells (ESCs), expression of GATA1s promoted megakaryopoiesis, but
      not erythropoiesis. Transcriptome analysis revealed a selective deficiency in the
      ability of GATA1s to activate erythroid-specific genes within populations of
      hematopoietic progenitors. Although its DNA-binding domain was intact, chromatin
      immunoprecipitation studies showed that GATA1s binding at specific erythroid
      regulatory regions was impaired, while binding at many nonerythroid sites,
      including megakaryocytic and myeloid target genes, was normal. Together, these
      observations indicate that lineage-specific GATA1 cofactor associations are
      essential for normal chromatin occupancy and provide mechanistic insights into
      how GATA1s mutations cause human disease. More broadly, our studies underscore
      the value of ESCs and iPSCs to recapitulate and study disease phenotypes. 

PMID- 25621502
TI  - Raspberry-like metamolecules exhibiting strong magnetic resonances.
AB  - We report a synthetic approach to produce raspberry-like plasmonic nanostructures
      with unusually strong magnetic resonances, termed raspberry-like metamolecules
      (raspberry-MMs). The synthesis based on the surfactant-assisted templated seed
      growth method allows for the simultaneous one-step synthesis and assembly of well
      insulated gold nanoparticles. The aromatic surfactant used for the syntheses
      forms a thin protective layer around the nanoparticles, preventing them from
      touching each other and making it possible to pack discrete nanoparticles at
      close distances in a single cluster. The resulting isotropic gold nanoparticle
      clusters (i.e., raspberry-MMs) exhibit unusually broad extinction spectra in the
      visible and near-IR region. Finite-difference time-domain (FDTD) modeling showed
      that the raspberry-MMs support strong magnetic resonances that contribute
      significantly to the broadband spectra. The strong magnetic scattering was also
      verified by far-field scattering measurements, which show that in the near-IR
      region the magnetic dipole resonance can be even stronger than the electric
      dipole resonance in these raspberry-MMs. Structural parameters such as the size
      and the number of gold nanoparticles composing raspberry-MMs can be readily tuned
      in our synthetic method. A series of syntheses with varying structure parameters,
      along with FDTD modeling and mode analyses of corresponding model structures,
      showed that the close packing of a large number of metal nanoparticles in
      raspberry-MMs is responsible for the unusually strong magnetic resonances
      observed here. 

PMID- 25621503
TI  - The positive effects of yerba mate (Ilex paraguariensis) in obesity.
AB  - The prevalence of obesity has increased worldwide over the past three decades.
      Global anti-obesity strategies focus on dietary and lifestyle modifications to
      slow the development of obesity. Research in the nutrition field has recently
      aroused considerable interest based on the potential of natural products to
      counteract obesity. Several studies have identified yerba mate (Ilex
      paraguariensis) as an excellent candidate. In this review, we evaluated the
      impact of yerba mate on obesity and obesity-related inflammation. Cellular
      studies demonstrate that yerba mate suppresses adipocyte differentiation and
      triglyceride accumulation and reduces inflammation. Animal studies show that
      yerba mate modulates signaling pathways that regulate adipogenesis, antioxidant,
      anti-inflammatory and insulin signaling responses. In summary, the data presented
      here showed that the use of yerba mate might be useful against obesity, improving
      the lipid parameters in humans and animal models. In addition, yerba mate
      modulates the expression of genes that are changed in the obese state and
      restores them to more normal levels of expression. In doing so, it addresses
      several of the abnormal and disease-causing factors associated with obesity.
      Protective and ameliorative effects on insulin resistance were also observed.
      Thus, as a general conclusion, it seems that yerba mate beverages and supplements
      might be helpful in the battle against obesity. 

PMID- 25621504
TI  - A pilot study to validate a standardized one-week salt estimation method
      evaluating salt intake and its sources for family members in China.
AB  - The objective of this study was to develop a new method named the "one-week salt
      estimation method" that could estimate an individual's salt intake and the
      sources of salt in the diet, and to evaluate this new method with a 24-h urine
      collection. The new method estimates salt intake from: (1) household cooking by
      weighing the family salt container and other high-salt condiments or sauces at
      the beginning and end of a week; (2) processed food according to established
      China food composition figures; and (3) cafeteria or restaurant meals using the
      results of previous studies. Consumption of salt additives and major salt
      contained foods and salt intake related eating habits were collected using a
      structured simple seven-day questionnaire. In order to validate the method, we
      studied 37 individuals from 11 families using the new method and 26 of these
      participants collected seven concurrent 24-h urine samples. The average salt
      intake for the 26 participants was 15.6+/-5.5 g/person/day (mean+/-standard
      deviation) by the 24-h urine collection and 13.7+/-6.5 g/person/day by the new
      method. The difference was 1.8+/-4.2 g/day/person (p=0.037). The Pearson
      correlation coefficient was 0.762 (p<0.001) and the partial correlation
      coefficient was 0.771 (p<0.001) when adjusted for family code. Bland-Altman Plot
      showed the average of the difference between the two methods was -1.83, with 95%
      limits of -10.1 to 6.5 g/person/day. The new method showed that 43.7% of salt
      intake came from household cooking (33.5% from cooking salt, 10.2% from other
      condiments and sauces), 12.9% from processed food, and 43.4% from eating out. In
      conclusion, despite its limitations of underestimating salt intake, the "one-week
      salt estimation method" is easier for people to implement and is likely to
      provide useful information that highlights the excessively high intake of salt
      and its sources, and in turn is helpful in guiding dietary salt reduction.

PMID- 25621506
TI  - Staphylococcus aureus ST6-t701 isolates from food-poisoning outbreaks (2006-2013)
      in Xi'an, China.
AB  - The aim of the study was to investigate the molecular epidemiologic of
      Staphylococcus aureus isolated from seven staphylococcal food-poisoning (SFP)
      outbreaks between 2006 and 2013 in Xi'an, northwest China. A total of seven S.
      aureus isolates associated with seven SFP outbreaks were obtained and
      characterized by determining the multilocus sequence typing, spa typing, pulsed
      field gel electrophoresis (PFGE), antimicrobial susceptibility, toxin and
      resistant genes. The results showed that S. aureus ST6-t701 (71.4%) was the most
      predominant clone, followed by ST5-t002 and ST59-t172 (each 14.3%). Seven
      different PFGE patterns were obtained. Moreover, resistance was most frequently
      observed to trimethoprim and penicillin (each 71.4%), followed by erythromycin
      (28.6%), ampicillin, clindamycin, and tetracycline (each 14.3%). All strains were
      susceptible to chloramphenicol, cefoxitin, oxacillin, amikacin, and vancomycin.
      Three of seven strains displayed resistance to three or more antimicrobials.
      Resistance genes were found as follows: linA/linA' (100%), blaZ (85.7%), tet(K),
      ermC, ermT, and ermB (each 14.3%). Other resistant genes were not detected. In
      addition, the most frequently identified exotoxin genes were seu, lukED, hla,
      hlb, hld (each 100%), followed by hlg and hlgv (each 85.7%), lukPV (71.4%), sea
      (57.1%), see (42.9%), etd (28.6%), and seb, sec, sed, sej, and sek (each 14.3%).
      The results indicated that S. aureus ST6-t701, with a high prevalence in the
      northwest of China, exhibited multidrug resistance and harbored multiple toxin
      and resistance genes. Therefore, strict hygienic and preventative measures should
      be taken in order to avoid the contamination of food by S. aureus and toxin
      production in foods. 

PMID- 25621505
TI  - Intestinal microbial dysbiosis and colonic epithelial cell hyperproliferation by
      dietary alpha-mangostin is independent of mouse strain.
AB  - Beverages and supplements prepared from mangosteen fruit are claimed to support
      gut health and immunity, despite the absence of supporting evidence from clinical
      trials. We recently reported that alpha-mangostin (alpha-MG), the most abundant
      xanthone in mangosteen fruit, altered the intestinal microbiome, promoted
      dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study
      was to determine whether induction of dysbiosis by dietary alpha-MG is limited to
      the C57BL/6J strain or represents a more generic response to chronic intake of
      the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and
      C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or
      diet containing 0.1% alpha-MG for four weeks. Dietary alpha-MG significantly
      altered the cecal and colonic microbiota in all four strains of mice, promoting a
      reduction in generally assumed beneficial bacterial groups while increasing the
      abundance of pathogenic bacteria. Consumption of alpha-MG was associated with
      reduced abundance of Firmicutes and increased abundance of Proteobacteria. The
      abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced
      in alpha-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was
      increased. Dietary alpha-MG also was associated with increased proliferation of
      colonic epithelial cells, infiltration of immune cells, infiltration of immune
      cells and increased fluid content in stool. These results suggest that ingestion
      of pharmacologic doses of xanthones in mangosteen-containing supplements may
      adversely alter the gut microbiota and should be used with caution. 

PMID- 25621507
TI  - Improving target cell specificity using a novel monovalent bispecific IgG design.
AB  - Monovalent bispecific IgGs cater to a distinct set of mechanisms of action but
      are difficult to engineer and manufacture because of complexities associated with
      correct heavy and light chain pairing. We have created a novel design, "DuetMab,"
      for efficient production of these molecules. The platform uses knobs-into-holes
      (KIH) technology for heterodimerization of 2 distinct heavy chains and increases
      the efficiency of cognate heavy and light chain pairing by replacing the native
      disulfide bond in one of the CH1-CL interfaces with an engineered disulfide bond.
      Using two pairs of antibodies, cetuximab (anti-EGFR) and trastuzumab (anti-HER2),
      and anti-CD40 and anti-CD70 antibodies, we demonstrate that DuetMab antibodies
      can be produced in a highly purified and active form, and show for the first time
      that monovalent bispecific IgGs can concurrently bind both antigens on the same
      cell. This last property compensates for the loss of avidity brought about by
      monovalency and improves selectivity toward the target cell. 

PMID- 25621508
TI  - Relationships Between Social-Emotional Intelligence and Sexual Risk Behaviors in
      Adolescent Girls.
AB  - Social-emotional intelligence (SEI) has been linked with a number of health
      behaviors in adolescent populations. However, little is known about the influence
      of SEI on sexual behavior. This study examined associations between three
      indicators of SEI (intrapersonal skills, interpersonal skills, stress management
      skills) and adolescent girls' sexual risk behaviors. Data come from a cross
      sectional sample of sexually active adolescent girls (ages 13 to 17 years) at
      high risk for pregnancy (N = 253), recruited from health care clinics in a
      Midwest metropolitan area during 2007 and 2008. Results of multivariable
      regression models controlling for participants' age and race/ethnicity indicated
      that each aspect of SEI was related to distinct sexual risk behaviors.
      Specifically, girls with greater intrapersonal skills had significantly fewer
      male sex partners in the past six months (b = -0.16). Participants with greater
      interpersonal skills reported earlier communication with their sexual partner
      about sexual risk (b = 0.14), and those with a better ability to manage stress
      reported more consistent condom use (b = 0.31). Study findings suggest that SEI
      may provide a protective buffer against sexual risk behaviors. Building
      adolescent girls' social and emotional skills may be an effective strategy for
      reducing their risk for early pregnancy and sexually transmitted infections. 

PMID- 25621510
TI  - Protein export into malaria parasite-infected erythrocytes: mechanisms and
      functional consequences.
AB  - Phylum Apicomplexa comprises a large group of obligate intracellular parasites of
      high medical and veterinary importance. These organisms succeed intracellularly
      by effecting remarkable changes in a broad range of diverse host cells. The
      transformation of the host erythrocyte is particularly striking in the case of
      the malaria parasite Plasmodium falciparum. P. falciparum exports hundreds of
      proteins that mediate a complex cellular renovation marked by changes in the
      permeability, rigidity, and cytoadherence properties of the host erythrocyte. The
      past decade has seen enormous progress in understanding the identity and function
      of these exported effectors, as well as the mechanisms by which they are
      trafficked into the host cell. Here we review these advances, place them in the
      context of host manipulation by related apicomplexans, and propose key directions
      for future research. 

PMID- 25621509
TI  - A structural perspective on the regulation of the epidermal growth factor
      receptor.
AB  - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that
      plays a critical role in the pathogenesis of many cancers. The structure of
      intact forms of this receptor has yet to be determined, but intense
      investigations of fragments of the receptor have provided a detailed view of its
      activation mechanism, which we review here. Ligand binding converts the receptor
      to a dimeric form, in which contacts are restricted to the receptor itself,
      allowing heterodimerization of the four EGFR family members without direct ligand
      involvement. Activation of the receptor depends on the formation of an asymmetric
      dimer of kinase domains, in which one kinase domain allosterically activates the
      other. Coupling between the extracellular and intracellular domains may involve a
      switch between alternative crossings of the transmembrane helices, which form
      dimeric structures. We also discuss how receptor regulation is compromised by
      oncogenic mutations and the structural basis for negative cooperativity in ligand
      binding. 

PMID- 25621511
TI  - Plasticity of DNA methylation in a nerve injury model of pain.
AB  - The response of the peripheral nervous system (PNS) to injury may go together
      with alterations in epigenetics, a conjecture that has not been subjected to a
      comprehensive, genome-wide test. Using reduced representation bisulfite
      sequencing, we report widespread remodeling of DNA methylation in the rat dorsal
      root ganglion (DRG) occurring within 24 h of peripheral nerve ligation, a
      neuropathy model of allodynia. Significant (P < 10(-4)) cytosine hyper- and hypo
      methylation was found at thousands of CpG sites. Remodeling occurred outside of
      CpG islands. Changes affected genes with known roles in the PNS, yet methylome
      remodeling also involved genes that were not linked to neuroplasticity by prior
      evidence. Consistent with emerging models relying on genome-wide methylation and
      RNA-seq analysis of promoter regions and gene bodies, variation of methylation
      was not tightly linked with variation of gene expression. Furthermore,
      approximately 44% of the dynamically changed CpGs were located outside of genes.
      We compared their positions with the intergenic, tissue-specific differentially
      methylated CpGs (tDMCs) of an independent experimental set consisting of liver,
      spleen, L4 control DRG, and muscle. Dynamic changes affected those intergenic
      CpGs that were different between tissues (P < 10(-15)) and almost never the
      invariant portion of the methylome (those CpGs that were identical across all
      tissues). Our findings-obtained in mixed tissue-show that peripheral nerve injury
      leads to methylome remodeling in the DRG. Future studies may address which of the
      cell types found in the DRG, such as specific groups of neurons or non-neuronal
      cells are affected by which aspect of the observed methylome remodeling.

PMID- 25621512
TI  - Strigolactones, a novel carotenoid-derived plant hormone.
AB  - Strigolactones (SLs) are carotenoid-derived plant hormones and signaling
      molecules. When released into the soil, SLs indicate the presence of a host to
      symbiotic fungi and root parasitic plants. In planta, they regulate several
      developmental processes that adapt plant architecture to nutrient availability.
      Highly branched/tillered mutants in Arabidopsis, pea, and rice have enabled the
      identification of four SL biosynthetic enzymes: a cis/trans-carotene isomerase,
      two carotenoid cleavage dioxygenases, and a cytochrome P450 (MAX1). In vitro and
      in vivo enzyme assays and analysis of mutants have shown that the pathway
      involves a combination of new reactions leading to carlactone, which is converted
      by a rice MAX1 homolog into an SL parent molecule with a tricyclic lactone
      moiety. In this review, we focus on SL biosynthesis, describe the hormonal and
      environmental factors that determine this process, and discuss SL transport and
      downstream signaling as well as the role of SLs in regulating plant development. 

PMID- 25621513
TI  - The polycomb group protein regulatory network.
AB  - Correct expression of specific sets of genes in time and space ensures the
      establishment and maintenance of cell identity, which is required for proper
      development of multicellular organisms. Polycomb and Trithorax group proteins
      form multisubunit complexes that antagonistically act in epigenetic gene
      repression and activation, respectively. The traditional view of Polycomb
      repressive complexes (PRCs) as executors of long-lasting and stable gene
      repression is being extended by evidence of flexible repression in response to
      developmental and environmental cues, increasing the complexity of mechanisms
      that ensure selective and properly timed PRC targeting and release of Polycomb
      repression. Here, we review advances in understanding of the composition,
      mechanisms of targeting, and function of plant PRCs and discuss the parallels and
      differences between plant and animal models. 

PMID- 25621514
TI  - Plant Adaptation to Acid Soils: The Molecular Basis for Crop Aluminum Resistance.
AB  - Aluminum (Al) toxicity in acid soils is a significant limitation to crop
      production worldwide, as approximately 50% of the world's potentially arable soil
      is acidic. Because acid soils are such an important constraint to agriculture,
      understanding the mechanisms and genes conferring resistance to Al toxicity has
      been a focus of intense research interest in the decade since the last article on
      crop acid soil tolerance was published in this journal. An impressive amount of
      progress has been made during that time that has greatly increased our
      understanding of the diversity of Al resistance genes and mechanisms, how
      resistance gene expression is regulated and triggered by Al and Al-induced
      signals, and how the proteins encoded by these genes function and are regulated.
      This review examines the state of our understanding of the physiological,
      genetic, and molecular bases for crop Al tolerance, looking at the novel Al
      resistance genes and mechanisms that have been identified over the past ten
      years. Additionally, it examines how the integration of molecular and genetic
      analyses of crop Al resistance is starting to be exploited for the improvement of
      crop plants grown on acid soils via both molecular-assisted breeding and
      biotechnology approaches. 

PMID- 25621515
TI  - Brachypodium distachyon and Setaria viridis: Model Genetic Systems for the
      Grasses.
AB  - The family of grasses encompasses the world's most important food, feed, and
      bioenergy crops, yet we are only now beginning to develop the genetic resources
      to explore the diversity of form and function that underlies economically
      important traits. Two emerging model systems, Brachypodium distachyon and Setaria
      viridis, promise to greatly accelerate the process of gene discovery in the
      grasses and to serve as bridges in the exploration of panicoid and pooid grasses,
      arguably two of the most important clades of plants from a food security
      perspective. We provide both a historical view of the development of plant model
      systems and highlight several recent reports that are providing these developing
      communities with the tools for gene discovery and pathway engineering. 

PMID- 25621516
TI  - Terrestrial ecosystems in a changing environment: a dominant role for water.
AB  - Transpiration--the movement of water from the soil, through plants, and into the
      atmosphere--is the dominant water flux from the earth's terrestrial surface. The
      evolution of vascular plants, while increasing terrestrial primary productivity,
      led to higher transpiration rates and widespread alterations in the global
      climate system. Similarly, anthropogenic influences on transpiration rates are
      already influencing terrestrial hydrologic cycles, with an even greater potential
      for changes lying ahead. Intricate linkages among anthropogenic activities,
      terrestrial productivity, the hydrologic cycle, and global demand for ecosystem
      services will lead to increased pressures on ecosystem water demands. Here, we
      focus on identifying the key drivers of ecosystem water use as they relate to
      plant physiological function, the role of predicted global changes in ecosystem
      water uses, trade-offs between ecosystem water use and carbon uptake, and
      knowledge gaps.

PMID- 25621517
TI  - The evolution of plant secretory structures and emergence of terpenoid chemical
      diversity.
AB  - Secretory structures in terrestrial plants appear to have first emerged as
      intracellular oil bodies in liverworts. In vascular plants, internal secretory
      structures, such as resin ducts and laticifers, are usually found in conjunction
      with vascular bundles, whereas subepidermal secretory cavities and epidermal
      glandular trichomes generally have more complex tissue distribution patterns. The
      primary function of plant secretory structures is related to defense responses,
      both constitutive and induced, against herbivores and pathogens. The ability to
      sequester secondary (or specialized) metabolites and defense proteins in
      secretory structures was a critical adaptation that shaped plant-herbivore and
      plant-pathogen interactions. Although this review places particular emphasis on
      describing the evolution of pathways leading to terpenoids, it also assesses the
      emergence of other metabolite classes to outline the metabolic capabilities of
      different plant lineages. 

PMID- 25621518
TI  - The mechanism and key molecules involved in pollen tube guidance.
AB  - During sexual reproduction of flowering plants, pollen tube guidance by pistil
      tissue is critical for the delivery of nonmotile sperm cells to female gametes.
      Multistep controls of pollen tube guidance can be divided into two phases:
      preovular guidance and ovular guidance. During preovular guidance, various female
      molecules, including stimulants for pollen germination and pollen tube growth,
      are provided to support tube growth toward the ovary, where the ovules are
      located. After entering the ovary, pollen tubes receive directional cues from
      their respective target ovules, including attractant peptides for precise,
      species-preferential attraction. Successful pollen tube guidance in the pistil
      requires not only nutritional and directional controls but also competency
      controls to make pollen tubes responsive to guidance cues, regulation to
      terminate growth once a pollen tube arrives at the target, and strategies to stop
      ovular attraction depending on the fertilization of female gametes. 

PMID- 25621519
TI  - Moving toward a comprehensive map of central plant metabolism.
AB  - Decades of intensive study have led to the discovery of the main pathways
      involved in central metabolism but only some of the pathways and regulatory
      networks in which they are embedded. In this review, we discuss techniques used
      to assemble these pathways into a systems biology framework that can enable
      accurate modeling of the response of central metabolism to changes, including
      ways to perturb metabolic systems and assemble the resulting data into a
      meaningful network. Critically, these networks are of such size and complexity
      that it is possible to derive them only if data from different groups can be
      comprehensively and meaningfully combined. We conclude that it is essential to
      establish common standards for the description of experimental conditions and
      data collection and to store this information in databases to which the whole
      community can contribute. 

PMID- 25621521
TI  - Palladium-catalyzed diastereoselective oxyarylation of 2-alkylindoles.
AB  - Diastereoselective oxyarylation of N-protected 2-alkylindoles with commercially
      available boronic acids and TEMPO as a mild oxidant to give N-protected 2-aryl-2
      alkyl-3-(2-chloroacetoxy)indolines is described. Reactions are easy to conduct,
      and product indolines containing a fully substituted C-center are obtained in
      good yields with good to excellent selectivities. 

PMID- 25621522
TI  - The Road To Cnidaria: History of Phylogeny of the Myxozoa.
AB  - Myxozoans are a clade of highly derived cnidarians. The phylogenetic identity of
      these extremely simplified parasites of aquatic vertebrates and invertebrates had
      long been uncertain, with all early classifications designating Myxozoa as
      protists. Though suggestions were frequently made that the infective spores of
      these parasites are multicellular and possibly of cnidarian origin, it would take
      a phylogenetic analysis of ultrastructural developmental characters in
      combination with rRNA gene sequences to verify the Myxozoa as secondarily reduced
      cnidarians, sister to the polypoidozoan parasite Polypodium hydriforme . While a
      series of subsequent molecular studies suggested hypotheses of Myxozoa as basal
      bilaterians, triploblasts, or even nematodes, phylogenomic analyses with improved
      taxon sampling corroborated the landmark paper that verified the cnidarian nature
      of this group. This review of the body of phylogenetic work on Myxozoa aims to
      clarify historical progress and current knowledge, as well as to emphasize the
      opportune position that myxozoan biologists now are in, to address fundamental
      questions of cell biology of these parasites as well as the evolution of animal
      life. 

PMID- 25621523
TI  - Aggregated effects of combining daily milk consumption and aerobic exercise on
      short-term memory and sustained attention among female students.
AB  - Regular aerobic exercise and milk consumption have been found to have positive
      effects on certain cognitive functions such as short-term memory and sustained
      attention. However, aggregated effects of combining these modalities have not
      been explored. This study examined the combined effects of milk supplementation
      and aerobic exercise on the short-term memory and sustained attention of female
      students aged 16 yr. (N = 81). The intervention involved serving of 250 ml of
      regular milk during school days and/or a 1-hr. aerobic exercise period twice per
      week for 6 weeks. The Digit Span Test and Digit Vigilance Test were used to
      measure short-term memory and sustained attention, respectively. The combination
      group (milk and exercise) and exercise group performed significantly better than
      did the milk and control groups in terms of short-term memory. No significant
      interaction or group differences were found for sustained attention. The results
      suggest benefits of regular exercise for students' short-term memory.

PMID- 25621524
TI  - The role of word choice and criterion on intentional memory.
AB  - The relationship between the criterion for choosing and the self-choice effects
      (greater recall in a self-choice compared to a forced-choice condition) on
      intentional memory was examined. Thirty-three female nursing school volunteers
      were administered 24 word pairs in a 2 * 2 design to assess the influence of
      motivation upon free recall. When word pairs were presented to participants, they
      were asked to choose a word to-be-remembered, either in a self-choice condition
      or a forced-choice condition. Words chosen by the participants were recalled more
      often than those chosen by the experimenter (forced choice). Thus, the self
      choice effect was greater for words chosen with a self-reference criterion
      compared to a metamemory criterion, supporting the integration hypothesis as the
      origin of the self-choice effect.

PMID- 25621525
TI  - Parental attachment as a mediator between parental social support and self-esteem
      as perceived by Korean sports middle and high school athletes.
AB  - This study examined whether parental attachment mediates the relationship between
      parental social support and self-esteem in Korean middle and high school
      athletes. 591 sports athletes attending middle and high schools that specialize
      in sport volunteered. Parental social support and parental attachment had a
      significant positive effect on self-esteem; parental attachment had a greater
      effect on self-esteem. In the structural relationship, direct effects of parental
      social support on self-esteem were weak, but indirect effects through parental
      attachment were strong. Therefore, parental attachment complementally mediated
      the relationship between parental social support and self-esteem. Metric
      invariance was supported for groups categorized by sex, region, and school level,
      confirming that the model could be applied to various groups.

PMID- 25621527
TI  - Discrimination between oral cancer and healthy tissue based on water content
      determined by Raman spectroscopy.
AB  - Tumor-positive resection margins are a major problem in oral cancer surgery. High
      wavenumber Raman spectroscopy is a reliable technique to determine the water
      content of tissues, which may contribute to differentiate between tumor and
      healthy tissue. The aim of this study was to examine the use of Raman
      spectroscopy to differentiate tumor from surrounding healthy tissue in oral
      squamous cell carcinoma. From 14 patients undergoing tongue resection for
      squamous cell carcinoma, the water content was determined at 170 locations on
      freshly excised tongue specimens using the Raman bands of the OH-stretching
      vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(
      1)). The results were correlated with histopathological assessment of hematoxylin
      and eosin stained thin tissue sections obtained from the Raman measurement
      locations. The water content values from squamous cell carcinoma measurements
      were significantly higher than from surrounding healthy tissue (p-value <
      0.0001). Tumor tissue could be detected with a sensitivity of 99% and a
      specificity of 92% using a cutoff water content value of 69%. Because the Raman
      measurements are fast and can be carried out on freshly excised tissue without
      any tissue preparation, this finding signifies an important step toward the
      development of an intraoperative tool for tumor resection guidance with the aim
      of enabling oncological radical surgery and improvement of patient outcome. 

PMID- 25621528
TI  - Comparison of advance medical directive inquiry and documentation for hospital
      inpatients in three medical services: implications for policy changes.
AB  - Following the introduction of the Patient Self-Determination Act of 1990, the
      Veterans Health Administration developed its own advance medical directive (AMD)
      policy, which most recently states that documentation is mandatory for all
      hospital patients in all settings. The object of this study was to assess the
      effectiveness of AMD documentation at a local Veterans Affairs Medical Center.
      AMD documentation was compared among three inpatient services: surgery, medicine,
      and psychiatry. Retrospective in nature, 594 inpatient cases were compared.
      Results revealed that, overall, the rate of AMD documentation was 37.7%. AMD
      documentation on surgery was statistically more frequent (45.6%) than for either
      medicine (33.2%) or psychiatry (34.5%). The difference between the numbers of
      days to AMD documentation for all three services was not statistically
      significant. While there was no statistically significant difference across
      gender, Caucasians had AMDs documented more frequently than African Americans (p
      < .001). Logistic regression reveals that social worker and physician
      intervention, not patient-specific variables, are the primary predictors of AMD
      incidence. Policy makers may need to consider the realities of hospital care,
      especially in emergency settings, and be more specific in the steps of
      implementation of the policy in the evenings, weekends, and holidays. True
      adherence to policy implementation may require hospital administrators to
      increase staff and educational efforts so that the concept of AMD communication
      and documentation is completely explained to all staff and patients. Policy
      should include an electronic record reminder that is renewed every 3 years and
      provisions for accommodating patients who arrive on weekends and holidays, with
      special awareness of the particular communication needs of minority groups. The
      study conclusions are that further inquiry is needed to understand these policy
      nuances to enable the Veterans Affairs Administration to improve its policies and
      performance in this important aspect of healthcare. 

PMID- 25621529
TI  - Photoelectrochemical water splitting promoted with a disordered surface layer
      created by electrochemical reduction.
AB  - The recent discovery of colored TiO2 indicated that the disordered surface layer
      over the TiO2 particles/photoelectrodes is beneficial for higher photocatalytic
      performance; however, the role of the disordered surface TiO2 layer is not well
      understood. Here, we report an electrochemical strategy for tuning the surface
      structure of TiO2 nanorod arrays (NRAs) and try to understand the role of the
      disordered surface TiO2 layer. Photoelectrodes of TiO2 NRAs with a disordered
      shell were prepared by an electrochemical reduction method. The photocurrent of
      the NRAs with a disordered shell can reach as high as ~1.18 mA/cm(2) at 1.23 V,
      which is 2.2 times of that of the pristine TiO2 NRAs. Our results show that the
      surface disordered layer not only improves the bulk charge separation but also
      suppresses the charge recombination at the electrode/electrolyte interface,
      acting as an efficient water oxidation cocatalyst of photoelectrochemical cell
      for solar water splitting. 

PMID- 25621530
TI  - A new "offset" analogue of the classical oxime-bridged [Mn(III)6] single-molecule
      magnets.
AB  - A new "offset" analogue of the classical [Mn6O2]-core oxime-bridged single
      molecule magnets is introduced with a modified stacking arrangement of the [Mn3O]
      units. Studies of the magnetic properties reveal antiferromagnetic exchange
      interactions, a spin S = 4 ground state and population of low-lying excited
      states. Slow relaxation of the magnetization can be detected, with a
      corresponding energy barrier of 35.8 K. Interpretation of these features is
      supported with high-frequency EPR studies, quantifying the easy-axis type
      magnetic anisotropy, leading to a biaxial system. Redox properties investigated
      by cyclic and differential pulse voltammetry reveal multiple irreversible redox
      processes. 

PMID- 25621532
TI  - Allosterically regulated unfolding of the A'alpha helix exposes the dimerization
      site of the blue-light-sensing aureochrome-LOV domain.
AB  - Aureochromes have been shown to act as blue-light-regulated transcription factors
      in algae in the absence of phototropins. Aureochromes comprise a light-, oxygen-,
      or voltage-sensitive (LOV) domain as a sensory module binding the flavin
      chromophore and a basic region leucine zipper (bZIP) domain as an effector. The
      domain arrangement in aureochromes with an N-terminal effector is inversed to
      other LOV proteins. To clarify the role of the linking A'alpha helix in
      signaling, we have investigated the LOV domain of aureochrome1a from the diatom
      alga Phaeodactylum tricornutum without the N-terminal A'alpha helix but with the
      C-terminal Jalpha helix. Results were analyzed in comparison to those previously
      obtained on the LOV domain with both flanking helices and on the LOV domain with
      the A'alpha helix but without the Jalpha helix. Fourier transform infrared
      difference spectroscopy provides evidence by a band at 1656 cm(-1) that the
      A'alpha helix unfolds in response to light. This unfolding takes place only in
      the presence and as a consequence of the unfolding of the Jalpha helix, which
      points to an allosteric regulation. Size exclusion chromatography shows the LOV
      domain to be dimeric in the absence and monomeric in the presence of the A'alpha
      helix, implying that the folded helix covers the dimerization site. Therefore,
      the A'alpha helix directly modulates the oligomerization state of the LOV domain,
      whereas the Jalpha helix acts as an allosteric regulator. Both the allosteric
      control and the light-induced dimerization have not been observed in phototropin
      LOV2 and point to a different signaling mechanism within the full-length
      proteins. 

PMID- 25621533
TI  - VUV photoionization cross sections of HO2, H2O2, and H2CO.
AB  - The absolute vacuum ultraviolet (VUV) photoionization spectra of the hydroperoxyl
      radical (HO2), hydrogen peroxide (H2O2), and formaldehyde (H2CO) have been
      measured from their first ionization thresholds to 12.008 eV. HO2, H2O2, and H2CO
      were generated from the oxidation of methanol initiated by pulsed-laser
      photolysis of Cl2 in a low-pressure slow flow reactor. Reactants, intermediates,
      and products were detected by time-resolved multiplexed synchrotron
      photoionization mass spectrometry. Absolute concentrations were obtained from the
      time-dependent photoion signals by modeling the kinetics of the methanol
      oxidation chemistry. Photoionization cross sections were determined at several
      photon energies relative to the cross section of methanol, which was in turn
      determined relative to that of propene. These measurements were used to place
      relative photoionization spectra of HO2, H2O2, and H2CO on an absolute scale,
      resulting in absolute photoionization spectra. 

PMID- 25621531
TI  - Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors.
AB  - The discovery/optimization of bis-aryl ureas as Limk inhibitors to obtain high
      potency and selectivity and appropriate pharmacokinetic properties through
      systematic SAR studies is reported. Docking studies supported the observed SAR.
      Optimized Limk inhibitors had high biochemical potency (IC50 < 25 nM), excellent
      selectivity against ROCK and JNK kinases (>400-fold), potent inhibition of
      cofilin phosphorylation in A7r5, PC-3, and CEM-SS T cells (IC50 < 1 MUM), and
      good in vitro and in vivo pharmacokinetic properties. In the profiling against a
      panel of 61 kinases, compound 18b at 1 MUM inhibited only Limk1 and STK16 with
      >=80% inhibition. Compounds 18b and 18f were highly efficient in inhibiting cell
      invasion/migration in PC-3 cells. In addition, compound 18w was demonstrated to
      be effective on reducing intraocular pressure (IOP) on rat eyes. Taken together,
      these data demonstrated that we had developed a novel class of bis-aryl urea
      derived potent and selective Limk inhibitors. 

PMID- 25621534
TI  - Life-cycle greenhouse gas assessment of Nigerian liquefied natural gas addressing
      uncertainty.
AB  - Natural gas (NG) has been regarded as a bridge fuel toward renewable sources and
      is expected to play a greater role in future global energy mix; however, a high
      degree of uncertainty exists concerning upstream (well-to-tank, WtT) greenhouse
      gas (GHG) emissions of NG. In this study, a life-cycle (LC) model is built to
      assess uncertainty in WtT GHG emissions of liquefied NG (LNG) supplied to Europe
      by Nigeria. The 90% prediction interval of GHG intensity of Nigerian LNG was
      found to range between 14.9 and 19.3 g CO2 eq/MJ, with a mean value of 16.8 g CO2
      eq/MJ. This intensity was estimated considering no venting practice in Nigerian
      fields. The mean estimation can shift up to 25 g CO2 eq when considering a
      scenario with a higher rate of venting emissions. A sensitivity analysis of the
      time horizon to calculate GHG intensity was also performed showing that higher
      GHG intensity and uncertainty are obtained for shorter time horizons, due to the
      higher impact factor of methane. The uncertainty calculated for Nigerian LNG,
      specifically regarding the gap of data for methane emissions, recommends
      initiatives to measure and report emissions and further LC studies to identify
      hotspots to reduce the GHG intensity of LNG chains. 

PMID- 25621535
TI  - Optically Controlled Signal Amplification for DNA Computation.
AB  - The hybridization chain reaction (HCR) and fuel-catalyst cycles have been applied
      to address the problem of signal amplification in DNA-based computation circuits.
      While they function efficiently, these signal amplifiers cannot be switched ON or
      OFF quickly and noninvasively. To overcome these limitations, a light-activated
      initiator strand for the HCR, which enabled fast optical OFF -> ON switching, was
      developed. Similarly, when a light-activated version of the catalyst strand or
      the inhibitor strand of a fuel-catalyst cycle was applied, the cycle could be
      optically switched from OFF -> ON or ON -> OFF, respectively. To move the
      capabilities of these devices beyond solution-based operations, the components
      were embedded in agarose gels. Irradiation with customizable light patterns and
      at different time points demonstrated both spatial and temporal control. The
      addition of a translator gate enabled a spatially activated signal to travel
      along a predefined path, akin to a chemical wire. Overall, the addition of small
      light-cleavable photocaging groups to DNA signal amplification circuits enabled
      conditional control as well as fast photocontrol of signal amplification. 

PMID- 25621536
TI  - Retrospective analysis of the recovery of orientation and memory during
      posttraumatic amnesia.
AB  - OBJECTIVE: Prospective monitoring of posttraumatic amnesia (PTA) is recommended
      following moderate to severe traumatic brain injury (TBI). However, few studies
      have examined the typical order in which items recover on PTA scales. Different
      methods have been used to define recovery, and the order reported is not
      consistent across the literature. The purpose of this study was to improve
      understanding of the progression of PTA by reporting the duration to recovery of
      items and categories on the Westmead Post-Traumatic Amnesia Scale (WPTAS)
      according to different criteria. METHOD: A retrospective analysis was conducted
      of 66 patients with TBI who were administered the WPTAS during hospital
      admission. The duration to recovery of items and categories was determined
      according to 3 criteria: first correct, correct 3 times in a row, and
      consistently correct. RESULTS: On the basis of the sample mean, date of birth
      (DOB), year, age, place, month, day, name, and memory for the 3 pictures
      recovered in this order according to all 3 criteria. However, the significance of
      differences between items and the order of recovery of categories depended on the
      criterion adopted. Although DOB recovered first in 74% of cases and the 3
      pictures last in 63% of cases, there was a high degree of individual variability
      in the precise sequence of recovery. CONCLUSIONS: The traditional view of PTA
      recovering in the order of person, place, time, and memory does not adequately
      describe the profile of recovery on the WPTAS. Considering the recovery of
      individual items is necessary to understand and account for individuals
      differences in the order of recovery.

PMID- 25621537
TI  - Association of auditory-verbal and visual hallucinations with impaired and
      improved recognition of colored pictures.
AB  - OBJECTIVE: A number of cognitive underpinnings of auditory hallucinations have
      been established in schizophrenia patients, but few have, as yet, been uncovered
      for visual hallucinations. In previous research, we unexpectedly observed that
      auditory hallucinations were associated with poor recognition of color, but not
      black-and-white (b/w), pictures. In this study, we attempted to replicate and
      explain this finding. Potential associations with visual hallucinations were
      explored. METHOD: B/w and color pictures were presented to 50 schizophrenia
      patients and 45 healthy individuals under 2 conditions of visual context
      presentation corresponding to 2 levels of visual encoding complexity. Then,
      participants had to recognize the target pictures among distractors. RESULTS:
      Auditory-verbal hallucinations were inversely associated with the recognition of
      the color pictures presented under the most effortful encoding condition. This
      association was fully mediated by working-memory span. Visual hallucinations were
      associated with improved recognition of the color pictures presented under the
      less effortful condition. Patients suffering from visual hallucinations were not
      impaired, relative to the healthy participants, in the recognition of these
      pictures. CONCLUSION: Decreased working-memory span in patients with auditory
      verbal hallucinations might impede the effortful encoding of stimuli. Visual
      hallucinations might be associated with facilitation in the visual encoding of
      natural scenes, or with enhanced color perception abilities.

PMID- 25621538
TI  - Executive functioning and risk for Alzheimer's disease in the cognitively intact:
      Family history predicts Wisconsin Card Sorting Test performance.
AB  - OBJECTIVE: Alzheimer's disease (AD) research typically focuses on memory.
      However, executive functioning (EF) deficits are also common among AD patients;
      these deficits are associated with decreased functioning in activities of daily
      living, an important criterion in diagnosing AD. A classic test of EF ability,
      the Wisconsin Card Sort Test (WCST), has demonstrated sensitivity to
      differentiating individuals with AD from healthy controls, discriminating AD
      groups based on disease severity, and distinguishing AD from other types of
      dementia. Such sensitivity to AD raises the possibility that the WCST is also
      sensitive to very early, preclinical differences between those who have
      heightened risk for AD and those with lower risks. METHOD: The current study,
      therefore, examined WCST performance in healthy, cognitively intact older adults
      with a first-degree (i.e., sibling or parent) family history (FH) of AD (n = 18)
      and those with no such FH of AD (n = 24). RESULTS: Results revealed significant
      group differences for Categories Achieved, Percent Conceptual Level Responses,
      Total Errors, Perseverative Errors, and Non-Perseverative Errors, with the FH+
      group consistently exhibiting poorer performance. Moreover, hierarchical
      regression analyses indicated that after accounting for age, sex, and education,
      FH significantly predicted all 5 of these variables. CONCLUSIONS: These results
      speak to the potential role of EF in bolstering the current understanding of
      early cognitive markers of future decline. Furthering what is known about the
      relationship between AD and nonmemory specific domains of cognition such as
      executive functioning may allow for better prediction of cognitive decline and
      potential progression to AD.

PMID- 25621539
TI  - Direct observation of ordered configurations of hydrogen adatoms on graphene.
AB  - Ordered configurations of hydrogen adatoms on graphene have long been proposed,
      calculated, and searched for. Here, we report direct observation of several
      ordered configurations of H adatoms on graphene by scanning tunneling microscopy.
      On the top side of the graphene plane, H atoms in the configurations appear to
      stick to carbon atoms in the same sublattice. Scanning tunneling spectroscopy
      measurements revealed a substantial gap in the local density of states in H
      contained regions as well as in-gap states below the conduction band due to the
      incompleteness of H ordering. These findings can be well explained by density
      functional theory calculations based on double-sided H configurations. In
      addition, factors that may influence H ordering are discussed. 

PMID- 25621540
TI  - Electroconvulsive therapy as viewed by german psychiatrists: a comparison of 3
      subgroups.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is a stigmatized treatment even among
      doctors. This restrains the accessibility of ECT for patients in need of this
      treatment. In Germany, the utilization of ECT is low as compared with other
      Western industrialized countries. However, increasing application rates of ECT in
      Germany indicate some degree of support from psychiatrists. Therefore, the
      present study examined the current attitudes among 3 subgroups of psychiatrists
      toward ECT. METHODS: A questionnaire was sent through e-mail to 423 psychiatric
      hospitals in the Federal Republic of Germany and through facsimile to 2550
      specialists working in private practice. One hundred eighty-three (43%) of the
      institutions applied ECT (ECT facilities) and 240 (57%) institutions did not
      apply (non-ECT facilities). RESULTS: Nine hundred eighty-three answers could be
      evaluated. One hundred fifteen (63%) of the 183 ECT facilities, 118 (49%) of the
      240 non-ECT facilities, and 751 (30%) of the 2500 specialists working in private
      practice responded. The general attitude toward ECT was favorable: most of the
      participants agreed that ECT is used less often than it should be to best serve
      patients' interests (61%-89%) and that it should be applied more often (54%-79%).
      Most of the participants thought that the image of ECT has improved among
      psychiatrists (61%-74%) but has not changed among fellow physicians, patients,
      and the general population. CONCLUSIONS: A surprisingly positive attitude toward
      ECT was found in our study among all 3 groups of German psychiatrists, which
      might further help improve patients' access to this treatment.

PMID- 25621541
TI  - Anticonvulsant Mechanisms of Electroconvulsive Therapy and Relation to
      Therapeutic Efficacy.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is held to confer anticonvulsant
      effects, although the role of rise in seizure threshold upon clinical effect is
      uncertain. This study investigated the relationship in a large, consecutive,
      retrospective sample of patients receiving ECT in Aberdeen. We have tested the
      hypotheses of previous authors to further examine the relationship between
      seizure and therapeutic effect as well as discuss the potential underlying
      neurobiological mechanisms. METHODS: All patients receiving ECT at the Royal
      Cornhill Hospital between 2000 and the end of 2008 were identified from the
      Scottish ECT Accreditation Network. Electroconvulsive therapy was administered
      twice weekly with a bifrontotemporal electrode placement using routine dosage
      schedules. Data were gathered from the Scottish ECT Accreditation Network and
      case notes regarding ECT course and clinical effect. RESULTS: The seizure
      threshold increased in 219 (94.4%) patients, stayed the same in 13 (5.6%)
      patients, and decreased in 0 patient (n = 232). No significant relationship was
      present between change in seizure threshold and change in Montgomery-Asberg
      Depression Rating Scale score (P = 0.39; Kendall tau b r = 0.047; n = 182),
      although responders did display greater increase in seizure threshold than
      nonresponders. CONCLUSIONS: Electroconvulsive therapy confers anticonvulsant
      effects in a consecutive sample of real-life patients. Neither initial seizure
      threshold nor magnitude of seizure threshold increase is a predictor of clinical
      response to ECT. A rise in seizure threshold is not essential for therapeutic
      effect but may represent an important marker of underlying neuronal state. The
      evidence reviewed in this article supports a link between neuroplastic effects of
      ECT and the evidenced rise in seizure threshold.

PMID- 25621542
TI  - Attitudes Toward Electroconvulsive Therapy Compared With Cardioversion.
AB  - AIM: The aim of this study was to examine the patient preference for
      electroconvulsive therapy and for cardioversion. The latter was regarded as a
      proxy control group because each patient had also experienced a life-threatening
      illness for which there were both pharmacological and electrical options
      available. METHODS: A retrospective, semistructured, telephone survey of patients
      from a public, rural Australian hospital who had received either
      electroconvulsive therapy or cardioversion was undertaken. RESULTS: Thirty-eight
      elderly patients were interviewed. Patients agreed that they would rather not
      have had their respective electrical treatments. However, both groups also rated
      their treatment as effective and agreed that they would have their treatment
      again. CONCLUSIONS: Despite understandable hesitancies, patients can choose
      treatments because they are helpful.

PMID- 25621543
TI  - Deep brain stimulation versus electroconvulsive therapy in Parkinson's disease.

PMID- 25621544
TI  - Recall of paralysis after the seizure with right unilateral ultrabrief technique.

PMID- 25621545
TI  - Transitions and growth.

PMID- 25621546
TI  - Treatment of periimplant mucositis: a systematic review of randomized controlled
      trials.
AB  - OBJECTIVE: To determine the most effective treatment for periimplant mucositis in
      patients with dental implants compared with a control group. MATERIALS AND
      METHODS: A PubMed (MEDLINE) literature search was made of articles published up
      until October 2013. Randomized controlled trials (RCTs) were stratified according
      to their level of quality using the Jadad scale and levels of evidence
      (University of Oxford). RESULTS: The combinations of search terms resulted in a
      list of 371 titles. Of these, 114 references were finally reviewed. Finally, 7
      RCTs fulfilled the inclusion criteria and were thus selected for inclusion in the
      systematic review. Chlorhexidine, the administration of azithromycin, and glycine
      powder air polishing are not effective for the treatment of periimplant
      mucositis. The only effective treatment seems to be the use of toothpaste with
      0.3% triclosan. CONCLUSION: Definitions of periimplant mucositis vary in the
      literature, and no clear criteria have been established regarding the diagnosis
      and treatment of this disorder. It highlights our lack of uniform treatment and
      need to establish additional research to fully provide effective treatments for
      this common condition. More, larger, and longer-term RCTs are needed in this
      periimplant disease.

PMID- 25621547
TI  - Comparison of two kinds of bovine bone in maxillary sinus augmentation: a
      histomorphometric study.
AB  - PURPOSE: The purpose of this study was to compare the histomorphometric from
      sinus augmentation with calcium-phosphate nanocrystal-coated bovine bone
      (Biocera) and anorganic bovine bone matrix (Bio-Oss). MATERIALS AND METHODS:
      Bilateral maxillary sinus augmentations were performed on 5 patients with delayed
      placement of implants. The lateral bony window was created using a piezoelectric
      saw, and the sinus membrane was elevated to make a new compartment. Bio-Oss was
      grafted in one sinus as the control group and Biocera was grafted in the opposite
      sinus as the test group. The bony window was repositioned over the bone graft. In
      all cases, samples were taken for biopsy at the time of implant placement, 6 to 8
      months after the grafting procedure. Independent t tests were used to examine
      between-group differences. RESULTS: None of the 5 patients had complications
      during healing period. Histomorphometrically, the Bio-Oss group showed 28.46% (+/
      5.28%) of newly formed bone. Biocera group showed 29.94% (+/-8.72%) of newly
      formed bone. Newly formed bone along inner surface of repositioned bony window
      area showed more mature and dense bone structure than new bone formed along bone
      graft. CONCLUSIONS: This study revealed that both bovine bone grafts were
      considered as suitable bone graft materials for maxillary sinus augmentation.

PMID- 25621548
TI  - Outcomes of topical applications of melatonin in implant dentistry: a systematic
      review.
AB  - BACKGROUND: Due to its antioxidant properties and its ability to detoxify free
      radicals, melatonin may interfere in the function of osteoclasts and thereby
      inhibit bone resorption. This inhibition of bone resorption may be enhanced by a
      reaction of indolamine in osteoclastogenesis and this may contribute to certain
      benefits in implantology. OBJECTIVE: This systematic literature review on the use
      of melatonin in implant dentistry aims to provide guidelines for clinicians.
      MATERIALS AND METHODS: PubMed, Science Direct, ISI Web of Knowledge, and the
      Cochrane base databases were used to identify articles published between 1999 and
      2013 on melatonin use in implant dentistry. Ten articles were selected consisting
      of 9 animal research studies and 1 review article, involving 60 Beagle dogs, 57
      rats, and 30 rabbits and a total of 352 implants. RESULTS: Melatonin, which is
      released into the saliva, has important implications in the oral cavity. To
      achieve dental implant stability, osseointegration involves a cascade of protein
      and cell apposition, vascular invasion, bone formation, and maturation. This
      process may be accelerated by local delivery of growth-promoting factors, as
      occurs with the topical application of melatonin over the implant surface.
      CONCLUSIONS: The experimental evidence suggests that topical applications of
      melatonin may be useful in oral surgery and implant dentistry, increasing bone-to
      implant contact values and new bone formation, and so improving the success and
      long-term survival of implant treatments.

PMID- 25621549
TI  - Morphological and chemical characteristics of different titanium surfaces treated
      by bicarbonate and glycine powder air abrasive systems.
AB  - OBJECTIVES: This in vitro study investigated possible morphological and chemical
      changes induced by glycine or sodium bicarbonate powder air polishing on machined
      and acid-etched titanium surfaces. MATERIALS AND METHODS: The glycine powder
      (granulometry <65 MUm) and sodium bicarbonate powder (granulometry <150 MUm) were
      applied on 2 machined healing abutments and on 2 acid-etched healing abutments.
      The samples were characterized by scanning electron microscopy coupled with
      energy dispersive x-ray spectroscopy. The analyses were performed at different
      steps: (1) as received, right after opening the abutment packaging; (2) after 20
      minutes air exposure; (3) after aging in artificial saliva; (4) after glycine or
      sodium bicarbonate powder air polishing for 5 seconds; (5) after repetition of
      steps 3 and 4 with longer time of polishing (20 seconds). CONCLUSIONS: Air
      polishing using glycine and sodium bicarbonate powder seemed to be safe for
      professional oral hygiene of titanium dental implants, although acid-etched
      abutments and abutments treated with bicarbonate harbored more salts. This might
      indicate a greater plaque accumulation in a clinical situation. However, this
      result has to be investigated in vivo to understand its clinical relevance.

PMID- 25621550
TI  - Evaluation of human periimplant soft tissues around nonsubmerged machined
      standard and platform-switched abutments.
AB  - PURPOSE: This study evaluated the effect of the platform-switching phenomenon,
      the use of a smaller diameter abutment on a larger diameter implant platform.
      Clinical and histological outcomes of the periimplant mucosa around titanium
      abutments in a nonsubmerged implant were evaluated. MATERIALS AND METHODS: Ten
      healthy adult patients, ranging from 27 to 65 years, participated in the study. A
      minimum of 2 endosseous implants with immediate abutment connection was placed
      per patient, 1 conventional and 1 platform-switched abutment. All sites for
      implant placement had an adequate zone of keratinized mucosa before surgical
      intervention. RESULTS: No clinical signs of inflammation were observed in the
      periimplant soft tissue mucosa, and healing was uneventful throughout the study
      period. Histological findings showed abnormally thick stratified squamous
      epithelium for both groups with few inflammatory cells in the connective tissue
      and none on the surface of the epithelium. CONCLUSION: Histological findings for
      both conventional and platform-switched implant-abutment configurations showed a
      similar composition of the soft tissue. These findings were in direct agreement
      with previous studies.

PMID- 25621551
TI  - Long-term clinical success of minimally and moderately rough oral implants: a
      review of 71 studies with 5 years or more of follow-up.
AB  - PURPOSE: The aim of the review was to compare the long-term clinical success of
      minimally and moderately rough dental implants in terms of differences in
      marginal bone loss and survival. MATERIALS AND METHODS: The pertinent literature
      was searched by using the PubMed database and requesting major manufacturers to
      provide reports of their commercially available dental implant systems. Clinical
      reports meeting the following criteria were reviewed: results of at least 5 years
      of follow-up, availability of baseline and follow-up radiographs including
      intraoral radiographs, and availability of marginal bone loss measurements from
      the baseline to the end of the follow-up period (5 years or more). All the
      recorded data were analyzed statistically. RESULTS: Seventy-one of 1202 articles
      met the inclusion criteria. Maxillary moderately rough implants were found to
      have significantly higher long-term survival rates than maxillary minimally rough
      implants; no such difference was noticed in the mandible. Significant marginal
      bone loss occurred around all the implants in the first year but stabilized
      thereafter, indicating the absence of progressive bone loss. CONCLUSION: The
      dental implant systems commercially available today have good long-term clinical
      success in terms of survival and marginal bone loss.

PMID- 25621552
TI  - Effect of buccal gap distance on alveolar ridge alteration after immediate
      implant placement: a microcomputed tomographic and morphometric analysis in dogs.
AB  - INTRODUCTION: The buccal bone resorption and the deformation of soft tissue
      contour are major problems of immediate implant treatment. This study aims to
      examine the changes of alveolar bone and soft tissue after immediate implant
      placement in different buccal gap distances. MATERIALS AND METHODS: Eight
      implants were placed randomly in the mandibular premolar sockets of 6 hybrid dogs
      with 1, 2, and 3 mm buccal gap distances. The dogs were killed after 2 or 4
      months for morphometric and microcomputed tomography analyses. DISCUSSION: After
      2 months, the 3-mm group had the highest buccal bone volume (BV), buccal
      bone/soft tissue thickness, and the lowest bone resorption. The wider the buccal
      gap, the more buccal bone and soft tissue were formed in this experimental
      setting. After 4 months, the buccal BV had decreased significantly in the 1-mm
      and the 2-mm groups, whereas the 3-mm group resisted to buccal bone resorption.
      This difference was more pronounced at the crest. CONCLUSION: The 3 mm is the
      optimal gap distance among the groups examined, which drastically influences the
      healing of bone and soft tissue surrounding the implants.

PMID- 25621553
TI  - Radiographic comparison of periimplant bone resorption and assessment of survival
      rates of 2 implant systems: a 10-year prospective multicenter study.
AB  - PURPOSE: The aim of this multicenter human clinical trial was to radiographically
      evaluate the marginal bone loss and to assess implant survival rate in patients
      treated using 2 different implant systems (Bio-Plant and Tuber-Plant) after 10
      years of loading. METHODS: Ninety-seven patients were selected, and 160 implants
      were inserted (72 Bio-Plant and 88 Tuber-Plant). Ten years later, 20 patients
      were lost at follow-up and 77 patients (126 implants; 67 Bio-Plant and 59 Tuber
      Plant) were recalled. After 10-year, the periimplant bone resorption was
      significantly lower (P = 0.0039) for Tuber-Plant (0.74 +/- 0.12 mm) than for Bio
      Plant (1.31 +/- 0.09 mm). The cumulative survival rate was 99.11%. CONCLUSION:
      Both implant systems demonstrated to be suitable for a long-term successful
      rehabilitation because of stable marginal bone levels and high survival rates
      after 10 years of functional loading.

PMID- 25621554
TI  - Different concentrations of glucose regulate proliferation and osteogenic
      differentiation of osteoblasts via the PI3 kinase/Akt pathway.
AB  - INTRODUCTION: The aim of this study was to investigate the effect of high glucose
      levels on proliferation and osteogenic ability in MC3T3-E1 osteoblastic cell line
      and to explore the regulatory mechanism of PI3 kinase (PI3K)/Akt signaling
      pathway. METHODS: The cultures were divided into 8 treatment groups: 4
      concentrations of glucose (5.5, 15.5, 25.5, and 35.5 mM) with or without
      LY294002. Cell proliferation, alkaline phosphatase (ALP) assay, alizarin red
      staining of mineralized nodule, osteogenic genes, and P-AKT expression were
      analyzed. RESULTS: Cell proliferation, ALP activity, mineralization, osteogenic
      genes (RUNX2, OSX, OPN, OCN) and P-AKT expression in MC3T3-E1 cells were
      increased, whereas the glucose concentration changed from 5.5 to 15.5 mM.
      However, when the glucose concentrations continue to increase from 25.5 to 35.5
      mM, the proliferation and osteogenic ability in MC3T3-E1 cells were gradually
      declined. Furthermore, these effects were significantly inhibited by PI3K/Akt
      inhibitor LY294002 at a glucose concentration of 15.5 mM, which was the optimum.
      CONCLUSIONS: Appropriate high glucose concentration (15.5 mM) can increase
      osteogenic differentiation by activating PI3K/Akt pathway in MC3T3-E1 cells, but
      exorbitant high glucose concentrations (25.5 and 35.5 mM) inhibited the
      biomineralization process. Findings indicated that PI3K/Akt pathway plays an
      important role in the physiological process of MC3T3-E1 cells.

PMID- 25621555
TI  - Effect of temperature on the dental implant osseointegration development in low
      density bone: an in vivo histological evaluation.
AB  - OBJECTIVES: To make an in vivo evaluation of the effects of 2 different bone
      temperatures, on the development of implant osseointegration, in low-density
      bone. MATERIALS AND METHODS: Fifteen implant osteotomic sites were prepared in
      the iliac crests of sheep. Before the implant insertion, 5 sites were heated to
      50 degrees C for 1 minute, 5 sites to 60 degrees C for 1 minute, and 5 sites were
      not overheated. Fifteen titanium dental implants (Cortex, Israel) were inserted.
      After a healing period of 2 months, the histomorphometric parameters calculated
      for each implant were the Bone-Implant Contact percentage (%BIC) and the
      infrabony pocket depth. Unpaired t test was applied to find statistical
      differences between groups. RESULTS: No implants failed. Statistical significant
      differences in %BIC and periimplant bone loss were found between the 60 degrees C
      group and control group. No significant differences were found between the 50
      degrees C group and control group, although bone suffering signs were present.
      CONCLUSION: An osteotomic site overheating up to 60 degrees C for 1 minute in low
      density bone, before implant insertion, did not lead to implant failure, but it
      induced significant crestal bone loss during healing and lower %BIC.

PMID- 25621556
TI  - Evaluation of bone formation after grafting with deproteinized bovine bone and
      mineralized allogenic bone.
AB  - PURPOSE: The purpose of this study was to evaluate the ability of new bone
      formation of deproteinized bovine bone (Bio-Oss) and mineralized allogenic bone
      (Tutoplast). MATERIALS AND METHODS: Sixty rats were divided into control and
      experimental groups (groups 1 and 2): control group, unfilled control; group 1,
      Bio-Oss; group 2, Tutoplast, respectively. The animals were killed after 6 and 12
      weeks, and newly formed bone was analyzed histomorphometrically. RESULTS: In the
      control group, some new bone formed in the rim of the defect area. In the group
      1, newly formed bone was thinner than the adjacent normal bone, and Bio-Oss
      particles were observed. In the group 2, showed a pattern of gradual fusion with
      adjacent bone, as well as particles in some areas, similar to the Bio-Oss-treated
      group. In the 12-week groups, the amount of new bone formation was significantly
      higher in the experimental groups than in the control group, and it was
      significantly higher in group 2 than in group 1. CONCLUSION: Although Tutoplast
      and Bio-Oss graft materials seem to be useful for bone grafts, Tutoplast showed
      more active new bone formation than Bio-Oss.

PMID- 25621557
TI  - Benign paroxysmal positional vertigo during lateral window sinus lift procedure:
      a case report and review.
AB  - PURPOSE: Benign paroxysmal positional vertigo (BPPV) is a possible and well
      documented complication after the osteotome internal sinus lift technique. But we
      report a case of unexpected BPPV complication after direct sinus lift by lateral
      approach for implant placement that was not reported till date. METHODS: A 30
      year-old woman had undergone direct sinus lift procedure by lateral window
      technique to replace her missing right molar with dental implant. The patient
      suffered with intense vertigo with nausea, vomiting, and aggravated when she
      changed the position of her head towards right immediately after procedure and
      was diagnosed with BPPV after the referral. CONCLUSION: We assume that prolonged
      hyperextended head position of iatrogenic origin can be the reason, in this case,
      for BPPV after direct lateral sinus lift procedure. There is also a possibility
      that the temporal relationship with the surgical area and surgical action by
      rotating tools during window preparation are also contributing factors.

PMID- 25621558
TI  - Modified protocol of the intraoral welding technique for immediate implant
      supported rehabilitation of the edentulous maxilla.
AB  - PURPOSE: The aim of this study was to report the outcomes of a treatment option
      of immediate loading with intraoral welding on only 4 implants for the
      restoration of patients with maxillary edentulism. MATERIALS AND METHODS:
      Seventeen consecutive patients were rehabilitated with 2 parallel and 2 tilted
      implants in the maxilla. Immediately after implant placement, angulated abutments
      were screwed on the implants to create better parallelism among the implants;
      thereafter, a titanium bar was intraorally welded to the welding pins to create a
      superstructure that rigidly splinted the implants. A fixed full-arch durable
      prosthesis was delivered on the same day of the surgery. The patients were
      followed for 26.5 months on average. RESULTS: During the follow-up time, 2
      implants were lost giving an implant survival rate of 97%. Nonetheless, all the
      prostheses remained in function and the prosthetic success was 100%. CONCLUSIONS:
      The rehabilitation of the edentulous maxilla with an immediately loaded full-arch
      prosthesis, obtained through intraoral welding on only 4 implants, is a
      functionally and esthetically successful treatment.

PMID- 25621559
TI  - Hydraulic sinus lift technique in future site development: clinical and
      histomorphometric analysis of human biopsies.
AB  - PURPOSE: The fluid-dynamic technique is characterized by the hydraulic detachment
      of the mucosa and simultaneous filling of the sub-Schneiderian space, with a
      graft material of paste-like consistency. MATERIALS AND METHODS: Authors
      performed 13 future site developments, on as many patients (4 men; 9 women; age
      49.46 +/- 12.44 years), using a nanocrystalline hydroxyapatite dispersed in an
      aqueous matrix as graft material. In the second stage, performed at 5.96 +/- 1.72
      months, 13 implants were placed after harvesting bone biopsies from the
      regenerated sites. The above samples were subjected to histological and
      histomorphometric analysis. The histomorphometric results were then compared with
      the bone density, measured in Hounsfield units. RESULTS: The average percentage
      of vital bone was of 29.08% +/- 14.7%, whereas the bone marrow and graft material
      were 59.75% +/- 11.19% and 11.16% +/- 10.88%, respectively. The percentage of
      vital bone has a significant correlation with the bone density of the recipient
      site (P = 0.003117). In contrast, the bone marrow (P = 0.08692) and the graft (P
      = 0.0799) do not show a significant correlation with this parameter. CONCLUSIONS:
      The results suggest the validity of the method in the regeneration of bone volume
      in the subantral region.

PMID- 25621560
TI  - Digital impressions for fabrication of definitive "all-on-four" restorations.
AB  - PURPOSE: The aim of this study was to assess the accuracy of digital impressions
      for "all-on-four" implant rehabilitation. MATERIALS AND METHODS: Patients
      edentulous in one or both jaws were randomly selected for this study. Complete
      arch immediately loaded prostheses supported by 4 implants (2 axial and 2 tilted)
      were placed. Five hours after implant placement, screw-retained full-arch
      temporary prostheses were positioned. After 4 months, a digital scan body was
      used to finalize definitive prosthesis. Radiographic assessments were obtained
      immediately after surgery and at each follow-up visit. Bone level measurements
      were reported at 6 and 12 months, and bone loss between upright and tilted
      implants was compared. RESULTS: Fourteen definitive cast metal frameworks
      prosthesis were delivered to the patients. No implant dropout occurred. All
      prosthesis were screwed onto the dental implants, and x-ray examinations revealed
      a bar-implant connection accuracy. The implant survival rate was 100% for all
      positioned implants. No statistically significant differences (P > 0.05) in
      crestal bone loss between tilted and upright implants were detected. CONCLUSIONS:
      Digital impression creates an accurate physical model significantly improving
      efficiencies for the dental team and streamlining the workflow.

PMID- 25621561
TI  - Chronic respiratory diseases: challenges in diagnosis and prevention.

PMID- 25621562
TI  - Asbestosis and environmental causes of usual interstitial pneumonia.
AB  - PURPOSE OF REVIEW: Recent epidemiologic investigations suggest that occupational
      and environmental exposures contribute to the overall burden of idiopathic
      pulmonary fibrosis (IPF). This article explores the epidemiologic and clinical
      challenges to establishing exposure associations, the current literature
      regarding exposure disease relationships and the diagnostic work-up of IPF and
      asbestosis patients. RECENT FINDINGS: IPF patients demonstrate a histopathologic
      pattern of usual interstitial pneumonia. In the absence of a known cause or
      association, a usual interstitial pneumonia pattern leads to an IPF diagnosis,
      which is a progressive and often terminal fibrotic lung disease. It has long been
      recognized that asbestos exposure can cause pathologic and radiographic changes
      indistinguishable from IPF. Several epidemiologic studies, primarily case control
      in design, have found that a number of other exposures that can increase risk of
      developing IPF include cigarette smoke, wood dust, metal dust, sand/silica and
      agricultural exposures. Lung mineralogic analyses have provided additional
      support to causal associations. Genetic variation may explain differences in
      disease susceptibility among the population. SUMMARY: An accumulating body of
      literature suggests that occupational and environmental exposure can contribute
      to the development of IPF. The impact of exposure on the pathogenesis and
      clinical course of disease requires further study.

PMID- 25621564
TI  - Registered report: transcriptional amplification in tumor cells with elevated c
      Myc.
AB  - The Lin et al. (2012), published in Cell in 2012. The experiments that will be
      replicated are those reported in Figures 3E and 3F. In these experiments,
      elevated levels of c-Myc in the P493-6 cell model of Burkitt's lymphoma results
      in an increase of the total level of RNA using UV/VIS spectrophotometry (Figure
      3E; Lin et al., 2012) and on the mRNA levels/cell for a large set of genes using
      digital gene expression technology (Figure 3F; Lin et al., 2012). The
      Reproducibility Project: Cancer Biology is a collaboration between the eLife. 

PMID- 25621565
TI  - Registered report: the CD47-signal regulated protein alpha (SIRPa) interaction is
      a therapeutic target for human solid tumors.
AB  - The Willingham et al., 2012, published in PNAS in 2012. The key experiments being
      replicated are those reported in Figure 6A-C and Table S4. In these experiments,
      Willingham et al., 2012 test the safety and efficacy of anti-CD47 antibody
      treatment in immune competent mice utilizing a syngeneic model of mammary tumor
      growth in FVB mice. The Reproducibility Project: Cancer Biology is a
      collaboration between the eLife. 

PMID- 25621566
TI  - Registered report: senescence surveillance of pre-malignant hepatocytes limits
      liver cancer development.
AB  - The Kang et al. (2011), published in Nature in 2011. The experiments that will be
      replicated are those reported in Figures 3B, 3C, 3E, and 4A. In these
      experiments, Kang et al. (2011) demonstrate the phenomenon of oncogene-induced
      cellular senescence and immune-mediated clearance of senescent cells after
      intrahepatic injection of NRAS (Figures 2I, 3B, 3C, and 3E). Additionally, Kang
      et al. (2011) show the specific necessity of CD4+ T cells for immunoclearance of
      senescent cells (Figure 4A). The Reproducibility Project: Cancer Biology is a
      collaboration between the eLife.

PMID- 25621567
TI  - Parent-Adolescent Patterns of Physical Activity, Sedentary Behaviors and Sleep
      Among a Sample of Overweight and Obese Adolescents.
AB  - BACKGROUND: The purpose of this study was to examine the association between
      parent and adolescent levels of physical activity, sedentary behaviors, and sleep
      among a group of overweight and obese adolescents. METHODS: Baseline data of
      parent-adolescent pairs who enrolled in a lifestyle modification intervention
      were analyzed for this study (n = 176). Participants completed questionnaires
      about their screen time (TV, video game, and computer time), wore an
      accelerometer for 8 days, and completed a sleep diary for 1 week. In total, 98
      parent-adolescent dyads provided valid data for the analyses. Multivariable
      regression analyses were conducted to assess the relationship between parent and
      adolescent's moderate-to-vigorous activity (MVPA), step counts, sedentary
      behaviors, and sleep duration. Analyses were split by weekday, weekday evening
      and weekend. RESULTS: Parent-adolescent MVPA was significantly associated on
      weekdays (b = 0.18; SE = 0.08; beta = 0.26), weekday evenings (b = 0.21; SE =
      0.08; beta = 0.28), and weekends (b = 0.29; SE = 0.12; beta = 0.27). This study
      found associations between parent-child video game time on weekends (b = 1.10; SE
      = 0.49; beta = 0.24) and computer time on weekdays (b = 0.42; SE = 0.19; beta =
      0.23). Adolescent sleep was associated with parental sleep on weekdays only (b =
      0.38; SE = 0.09; beta = 0.46). CONCLUSION: The findings warrant further
      investigation into the direction and mechanism of the relationship between parent
      and adolescent weight related behaviors.

PMID- 25621569
TI  - Potential of a Sports Club-Based Exercise Program for Improving Physical Activity
      in Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Although the infrastructure of Austrians' sports clubs is well
      developed, exercise classes for people suffering from type II diabetes mellitus
      (T2DM) do not exist. This feasibility study evaluates factors for participating
      in target group specific exercise courses (TGSEC) and changes in physical
      activity. METHODS: This intervention study was performed in 22 communities of
      Austria. Initial TGSEC were offered to T2DM patients over 2 months. Participants
      were surveyed at 4 time points with a questionnaire: before the program, 2, 6 and
      12 months after the initial questionnaire. RESULTS: 881 patients aged 59.0 (SD:
      9.6) years took part in TGSEC. At baseline a lack of suitable exercise groups
      prevented 51% from being active. 58% were encouraged by the medical sector. After
      12 months the weekly time spent on exercise training was increased from 1.40 (SD:
      2.55) hours to 2.15 (SD: 3.00) hours (P < .001). The dropout rate during the
      first 2 months was 12.9%. The rate of return for the 12 months questionnaire was
      42%. CONCLUSION: TGSEC provided by sports clubs attract people suffering from
      T2DM and effectively enhance physical activity.

PMID- 25621568
TI  - Effect of surgery on pancreatic tumor-dependent lymphocyte asset: modulation of
      natural killer cell frequency and cytotoxic function.
AB  - OBJECTIVES: Tumor burden and invasiveness establish a microenvironment that
      surgery could alter. This study shows a comprehensive analysis of size, dynamics,
      and function of peripheral lymphocyte subsets in pancreatic cancer patients
      before and at different times after duodenopancreatectomy. METHODS: Lymphocyte
      frequency and natural cytotoxicity were evaluated by flow cytometry and in vitro
      assay on peripheral blood from initial and advanced-stage pancreatic cancer
      patients before (BS), at day 7 (PS7), and at day 30 (PS30) after surgery.
      RESULTS: An increase in natural killer (NK) cells and the diminution of B-cells
      occurred at PS30, whereas cytotoxicity decreased at PS7. The positive correlation
      between NK frequency and cytotoxicity at BS and PS7 revealed an altered NK
      behavior. The elevation of NK cell frequency at PS30, an initial defect in
      CD56bright NK, and the aberrant correlation between NK frequency and cytotoxicity
      remained significant in advanced-stage patients, whereas the diminution of NK
      cytotoxicity only affected initial stage patients. CONCLUSIONS: The NK cell
      functional ability is altered in presurgery patients; duodenopancreatectomy is
      associated with short-term impairment of NK function and with a long-term NK cell
      augmentation and reversion of the aberrant NK behavior, which may impact on
      immunosurveillance against residual cancer.

PMID- 25621576
TI  - Specific foreknowledge reduces auditory distraction by irrelevant speech.
AB  - In a series of experiments, it was tested whether distraction by changing-state
      irrelevant speech is inevitable or can be modulated by foreknowledge of an
      imminent to-be-ignored distractor sequence. Participants were required to
      remember visually presented digits while ignoring background speech. In the
      foreknowledge condition of Experiment 1, the upcoming to-be-ignored sentence was
      presented auditorily and visually before each trial. With specific foreknowledge,
      the changing-state irrelevant sound effect (here, increased disruption by
      sentences compared with repeated words) was significantly attenuated relative to
      a condition without foreknowledge. This finding was replicated in Experiment 2,
      in which the information about the upcoming auditory distractor speech was
      presented only in the visual modality. Experiment 3 showed that only specific
      foreknowledge of the auditory distractor material has beneficial effects on the
      ability to ignore distraction. The mere notification that an unspecified
      distractor sentence would be presented next had no effect on distraction. In
      Experiment 4, there was only a small and not statistically significant reduction
      of the irrelevant speech effect when lists of randomly selected words were used
      as distractor material, suggesting that foreknowledge effects are more pronounced
      for highly variable, meaningful distractor material. We conclude that the
      disruption of short-term memory by irrelevant speech is not purely a stimulus
      driven process that is immune to top-down control. A significant proportion of
      the effect can be modulated by specific knowledge about an imminent distractor
      sequence.

PMID- 25621577
TI  - The influence of verbal and spatial working memory load on the time course of the
      Simon effect.
AB  - The Simon effect refers to the relatively poorer response times and accuracy when
      responding to targets that appear in a task-irrelevant spatial location that is
      incongruent with the location of the correct response key, compared with targets
      that appear in spatially congruent locations. Like Stroop and flanker effects,
      the Simon effect is thought to result from conflict between an irrelevant
      response tendency and an intended response. Because attentional control has been
      linked to conflict resolution, the Simon task has been proffered as a possible
      tool for measuring the efficacy of executive control mechanisms. These mechanisms
      are also involved in working memory (WM) processes, and are thought to be
      responsible for maintaining information in the presence of continued processing
      or distraction. The present study investigated the interface between WM and
      attention by examining the time course of the Simon effect over the response time
      distributions under varying WM load conditions. Participants completed verbal 0
      back, spatial 0-back, verbal 2-back, and spatial 2-back tasks. Results show that
      the Simon effect is diminished in high WM load tasks compared with low-load
      tasks, and that the Simon effect interacts with the spatial task domain such that
      the effect persists across the distribution of response times. In contrast, the
      Simon effect peaks and decays in verbal tasks. The results demonstrate that the
      Simon effect interacts with WM load and task domain. The results suggest that the
      effect is more modifiable than expected, and support a complex interface between
      WM and attentional control.

PMID- 25621578
TI  - Foreign language learning in French speakers is associated with rhythm
      perception, but not with melody perception.
AB  - There has been increasing interest in links between language and music. Here, we
      investigate the relation between foreign language learning and music perception.
      We administered tests measuring melody and rhythm perception as well as a
      questionnaire on musical and foreign language experience to 147 monolingual
      French speakers. As expected, we found that musicians had better melody and
      rhythm perception than nonmusicians and that, among musicians, there was a
      positive correlation between the total number of years of music training and test
      scores. Crucially, we also found a positive correlation between the total number
      of years learning foreign languages and rhythm perception, but we found no such
      relation with melody perception. Moreover, the degree to which participants were
      better at rhythm than melody perception was also related to foreign language
      experience. Results suggest that both music training and learning foreign
      languages (primarily English, Spanish, and German in our sample) are related to
      French speakers' perception of rhythm, but not to their perception of melody.
      These results are discussed with respect to the rhythmic properties of French and
      suggest a common perceptual basis for rhythm in language and music.

PMID- 25621579
TI  - Does expert perceptual anticipation transfer to a dissimilar domain?
AB  - The purpose of this experiment was to extend theoretical understanding of
      transfer of learning by investigating whether expert perceptual anticipation
      skill transfers to a dissimilar domain. The capability of expert and near-expert
      rugby players as well as novices to anticipate skill type within rugby (learning
      sport) was first examined using a temporal occlusion paradigm. Participants
      watched video footage of an opponent performing rugby skill types that were
      temporally occluded at different points in the opponent's action and then made a
      written prediction. Thereafter, the capability of participants to transfer their
      anticipation skill to predict pitch type in baseball (transfer sport) was
      examined. Participants watched video footage of a pitcher throwing different
      pitch types that were temporally occluded and made a written prediction. Results
      indicated that expert and near-expert rugby players anticipated significantly
      better than novices across all occlusion conditions. However, none of the skill
      groups were able to transfer anticipation skill to predict pitch type in
      baseball. The findings of this paper, along with existing literature, support the
      theoretical prediction that transfer of perceptual anticipation is expertise
      dependent and restricted to similar domains.

PMID- 25621580
TI  - Referent expressions and gaze: reference type influences real-world gaze cue
      utilization.
AB  - Gaze cues are used alongside language to communicate. Lab-based studies have
      shown that people reflexively follow gaze cue stimuli, however it is unclear
      whether this affect is present in real interactions. Language specificity
      influences the extent to which we utilize gaze cues in real interactions, but it
      is unclear whether the type of language used can similarly affect gaze cue
      utilization. We aimed to (a) investigate whether automatic gaze following effects
      are present in real-world interactions, and (b) explore how gaze cue utilization
      varies depending on the form of concurrent language used. Wearing a mobile eye
      tracker, participants followed instructions to complete a real-world search task.
      The instructor varied the determiner used (featural or spatial) and the presence
      of gaze cues (absent, congruent, or incongruent). Congruent gaze cues were used
      more when provided alongside featural references. Incongruent gaze cues were
      initially followed no more than chance. However, unlike participants in the no
      gaze condition, participants in the incongruent condition did not benefit from
      receiving spatial instructions over featural instructions. We suggest that
      although participants selectively use informative gaze cues and ignore unreliable
      gaze cues, visual search can nevertheless be disrupted when inherently spatial
      gaze cues are accompanied by contradictory verbal spatial references.

PMID- 25621581
TI  - "Pseudoextinction": asymmetries in simultaneous attentional selection.
AB  - We report robust visual-field asymmetries associated with selecting simultaneous
      targets. One letter embedded in a rapid serial visual presentation (RSVP) of
      letters was encircled by a white ring, cueing it as the target to report. In some
      conditions, 2 RSVP streams were presented concurrently, and targets appeared
      simultaneously in both. When only 1 stream was cued, performance was similar
      regardless of whether it was in the left or right visual field. Cueing 2 streams
      barely affected performance in the left stream, but performance in the right
      stream suffered markedly. We term this phenomenon pseudoextinction, by analogy to
      pseudoneglect whereby observers bisect lines to the left of center. Such
      attentional asymmetries are often believed to originate from a processing
      imbalance between the 2 cerebral hemispheres. But pseudoextinction also occurred
      with vertically arrayed streams, with higher efficacy in the superior than in the
      inferior stream. Mixture modeling of errors indicated that pseudoextinction did
      not affect the temporal precision or latency of selection episodes; rather, only
      the efficacy of selection suffered. These findings lead us to suggest that
      pseudoextinction arises because perceptual traces are activated simultaneously in
      a visual buffer, but must be tokenized serially. Observers succeed in selecting
      simultaneous targets because trace activation occurs in parallel. However,
      observers often fail to report both targets because tokenization proceeds
      serially: While 1 target is being tokenized, the other's trace may decay below
      the activation level necessary for tokenization.

PMID- 25621582
TI  - Expectancy-based modulations of lag-1 sparing and extended sparing during the
      attentional blink.
AB  - Over 20 years of research has shown that impairments in the identification of
      sequential targets-known as the attentional blink-are often eliminated when 2 or
      more targets are presented in direct succession. Such instances of lag-1 sparing
      and, more recently, extended sparing are widely attributed to the fact that
      directly successive visual inputs that possess common characteristics can be
      processed during an extended attentional window. Critically, this explanation
      implies that direct temporal succession and shared characteristics are sufficient
      to result in sparing. Here, I test this proposition directly by varying the
      probability of successive targets appearing during an experimental session.
      Across 5 experiments, I show that probability manipulations significantly affect
      the magnitude of sparing, with less sparing when the probability of a target
      appearing is relatively low. This outcome cannot be explained by resource shifts
      between targets, errors in perception of target order, or practice effects.
      Instead, the results suggest that sparing is determined not only by temporal
      contiguity and shared target characteristics but also by endogenous control
      processes that directly affect the duration of the attentional window.

PMID- 25621584
TI  - The pupillary light response reflects eye-movement preparation.
AB  - When the eyes are exposed to an increased influx of light, the pupils constrict.
      The pupillary light response (PLR) is traditionally believed to be purely
      reflexive and not susceptible to cognitive influences. In contrast to this
      traditional view, we report that preparation of a PLR occurs in parallel with
      preparation of a saccadic eye movement toward a bright (or dark) stimulus, even
      before the eyes set in motion. Participants fixated a central gray area and made
      a saccade toward a peripheral target. Using gaze-contingent display changes, we
      manipulated whether or not the brightness of the target background was the same
      during and after saccade preparation. More specifically, on some trials we
      changed the brightness of the target background during the saccade, thus
      dissociating the preparatory PLR (i.e., to the brightness of the target
      background before the saccade) from the regular PLR (i.e., to the brightness
      after the saccade). We show that preparation triggers a pupillary response to the
      brightness of a to-be-fixated target background already before the eyes have
      landed on it. We link our findings to the presaccadic shift of attention: The
      pupil prepares to adjust its size to the brightness of a to-be-fixated stimulus
      as soon as attention covertly shifts toward that stimulus. Our findings
      illustrate that the PLR is a dynamic movement that is tightly linked to visual
      attention and eye-movement preparation.

PMID- 25621583
TI  - Metrical expectations from preceding prosody influence perception of lexical
      stress.
AB  - Two visual-world experiments tested the hypothesis that expectations based on
      preceding prosody influence the perception of suprasegmental cues to lexical
      stress. The results demonstrate that listeners' consideration of competing
      alternatives with different stress patterns (e.g., 'jury/gi'raffe) can be
      influenced by the fundamental frequency and syllable timing patterns across
      material preceding a target word. When preceding stressed syllables distal to the
      target word shared pitch and timing characteristics with the first syllable of
      the target word, pictures of alternatives with primary lexical stress on the
      first syllable (e.g., jury) initially attracted more looks than alternatives with
      unstressed initial syllables (e.g., giraffe). This effect was modulated when
      preceding unstressed syllables had pitch and timing characteristics similar to
      the initial syllable of the target word, with more looks to alternatives with
      unstressed initial syllables (e.g., giraffe) than to those with stressed initial
      syllables (e.g., jury). These findings suggest that expectations about the
      acoustic realization of upcoming speech include information about metrical
      organization and lexical stress and that these expectations constrain the initial
      interpretation of suprasegmental stress cues. These distal prosody effects
      implicate online probabilistic inferences about the sources of acoustic-phonetic
      variation during spoken-word recognition.

PMID- 25621586
TI  - Character order processing in Chinese reading.
AB  - We explored how character order information is encoded in isolated word
      processing or Chinese sentence reading in 2 experiments using a masked priming
      paradigm and a gaze-contingent display-change paradigm. The results showed that
      response latencies in the lexical decision task and reading times on the target
      word region were longer in the unrelated condition (the prime or the preview was
      unrelated with the target word) than the transposed-character condition (the
      prime or the preview was a transposition of the 2 characters of the target word),
      which were respectively longer than in the identity condition (the prime or
      preview was identical to the target word). These results show that character
      order is encoded at an early stage of processing in Chinese reading, but
      character position encoding was not strict. We also found that character order
      encoding was similar for single-morpheme and multiple-morpheme words, suggesting
      that morphemic status does not affect character order encoding. The current
      results represent an early contribution to our understanding of character order
      encoding during Chinese reading.

PMID- 25621587
TI  - Validation and reproducibility of a semi-quantitative FFQ as a measure of dietary
      intake in adults from Puerto Rico.
AB  - OBJECTIVE: We aimed to assess the relative validity and reproducibility of a semi
      quantitative FFQ in Puerto Rican adults. DESIGN: Participants completed an FFQ,
      followed by a 6 d food record and a second administration of the FFQ, 30 d later.
      All nutrients were log transformed and adjusted for energy intake. Statistical
      analyses included correlations, paired t tests, cross-classification and Bland
      Altman plots. SETTING: Medical Sciences Campus, University of Puerto Rico.
      SUBJECTS: Convenience sample of students, employees and faculty members (n 100,
      >=21 years). Data were collected in 2010. RESULTS: A total of ninety-two
      participants completed the study. Most were young overweight females. All
      nutrients were significantly correlated between the two FFQ, with an average
      correlation of 0.61 (range 0.43-0.73) and an average difference of 4.8 % between
      them. Most energy-adjusted nutrients showed significant correlations between the
      FFQ and food record, which improved with de-attenuation and averaged 0.38 (range
      0.11-0.63). The lowest non-significant correlations (<=0.20) were for trans-fat,
      n 3 fatty acids, thiamin and vitamin E. Intakes assessed by the FFQ were higher
      than those from the food record by a mean of 19 % (range 4-44 %). Bland-Altman
      plots showed that there was a systematic trend towards higher estimates with the
      FFQ, particularly for energy, carbohydrate and Ca. Most participants were
      correctly classified into the same or adjacent quintile (average 66 %) by both
      methods with only 3 % gross misclassification. CONCLUSIONS: This semi
      quantitative FFQ is a tool that offers relatively valid and reproducible
      estimates of energy and certain nutrients in this group of mostly female Puerto
      Ricans.

PMID- 25621589
TI  - Making a decision to forgive.
AB  - Prominent models and interventions designed to promote forgiveness have
      distinguished one's decision to forgive from achieving forgiveness as an end
      state, but because of a lack of a strong measure, there is a weak research base
      on making a decision to forgive. Thus, in three studies, the authors developed
      the Decision to Forgive Scale (DTFS) and examined evidence for its reliability
      and construct validity. The article focused on distinguishing making a decision
      to forgive from achieved level of forgiveness. Scores on the DTFS showed evidence
      of reliability, with Cronbach's alpha coefficients ranging from .92 to .94, and a
      1-week temporal stability coefficient of .68. Using several strategies, the
      authors demonstrated that the DTFS is empirically distinct from the Transgression
      Related Interpersonal Motivations scale (TRIM; McCullough et al., 1998). Namely,
      a 3-factor confirmatory factor analysis that included the DTFS and the 2 TRIM
      subscales showed excellent fit, suggesting these instruments assess 3 different
      constructs. The DTFS was only moderately related to the TRIM subscales, was more
      strongly related to stage of change than the TRIM, and predicted subsequent TRIM
      scores in a cross-lagged model. Finally, although decisions to forgive generally
      suggested greater forgiveness, these constructs interacted to predict existential
      distress. Namely, as decisional forgiveness increased, revenge was more strongly
      related to existential distress. Overall, the DTFS shows considerable promise for
      further clinical and basic research applications.

PMID- 25621588
TI  - Efficacy of a self-forgiveness workbook: a randomized controlled trial with
      interpersonal offenders.
AB  - The present study tested the efficacy of a 6-hr self-directed workbook
      intervention designed to increase self-forgiveness and reduce self-condemnation
      among perpetrators of interpersonal offenses. University students (N = 204) were
      randomly assigned to either an immediate treatment or wait-list control
      condition, and assessments were administered on 3 occasions. Treatment led to
      increases in self-forgiveness and decreases in self-condemnation. Stronger
      treatment effects were associated with (a) lower levels of dispositional self
      forgivingness, (b) higher levels of transgression severity, and (c) higher dose
      of treatment. In summary, the workbook appeared to facilitate self-forgiveness
      among perpetrators of interpersonal wrongdoing, though replication trials are
      needed to build from these preliminary findings.

PMID- 25621590
TI  - The temporal order of change in daily mindfulness and affect during mindfulness
      based stress reduction.
AB  - Increases in mindfulness are assumed to lead to improvements in psychological
      well-being during mindfulness-based treatments. However, the temporal order of
      this association has received little attention. This intensive longitudinal study
      examines whether within-person changes in mindfulness precede or follow changes
      in negative affect (NA) and positive affect (PA) during a mindfulness based
      stress reduction (MBSR) program. This study also examines interindividual
      differences in the association between mindfulness and affect and possible
      predictors of these differences. Mindfulness, NA, and PA were assessed on a daily
      basis in 83 individuals from the general population who participated in an MBSR
      program. Multilevel autoregressive models were used to investigate the temporal
      order of changes in mindfulness and affect. Day-to-day changes in mindfulness
      predicted subsequent day-to-day changes in both NA and PA, but reverse
      associations did not emerge. Thus, changes in mindfulness seem to precede rather
      than to follow changes in affect during MBSR. The magnitude of the effects
      differed substantially between individuals, showing that the strength of the
      relationship between mindfulness and affect is not the same for all participants.
      These between-subjects differences could not be explained by gender, age, level
      of education, average level of mindfulness home practice, or baseline levels of
      mindfulness and affect. Mindfulness home practice during the day did predict
      subsequent increases in mindfulness. The findings suggest that increasing
      mindfulness on a daily basis can be a beneficial means to improve daily
      psychological well-being.

PMID- 25621591
TI  - Effects of manure-application practices on curli production by Escherichia coli
      transported through soil.
AB  - The release of Escherichia coli into the environment from untreated manure can
      pose a threat to human health. Environmental survival of E. coli has been linked
      to extracellular fibers called curli. We investigated the effect of manure
      management (surface application followed by incorporation versus immediate
      incorporation) on the relative abundance of curli-producing E. coli in subsurface
      drainage effluent. Samples were collected from three dairy farms. The proportion
      of curli-producing E. coli in the manure storage facilities was uniform across
      the farms. However, the abundance of curli-producing E. coli was much greater (P
      < 0.05) in the tile drains of farms performing surface application of manure than
      in the tile drain of the farm that incorporated manure. This field observation
      was tested with controlled soil column experiments; the abundance of curli
      producing E. coli in soil column effluents was greater (P < 0.05) when manure was
      surface-applied than when it was incorporated. Our findings suggest selection
      pressures resulting from the different manure application methods affected curli
      production by E. coli isolates transported through soil. Given the importance of
      curli production in pathogenesis, this work highlights the effect that manure
      management strategies may have on pathogenesis-associated phenotypes of bacteria
      in agricultural subsurface runoff. 

PMID- 25621592
TI  - Leader narcissism and follower outcomes: The counterbalancing effect of leader
      humility.
AB  - [Correction Notice: An Erratum for this article was reported in Vol 100(4) of
      Journal of Applied Psychology (see record 2015-29666-001). The last name of the
      second author was misspelled in the Online First version of the article. All
      versions of this article have been corrected.] In response to recent calls to
      theorize and examine how multiple leader characteristics may work together in
      their effects, the current research examines how leader narcissism and humility
      interact to predict perceived leader effectiveness and follower (i.e., direct
      report) job engagement and performance. Although an examination of leaders who
      are narcissistic yet humble may seem oxymoronic and even paradoxical, researchers
      have suggested that seemingly contradictory personal attributes may exist
      simultaneously and may actually work together to produce positive outcomes.
      Results from survey data from followers and leaders working for a large health
      insurance organization showed that the interaction of leader narcissism and
      leader humility is associated with perceptions of leader effectiveness, follower
      job engagement, and subjective and objective follower job performance. Together,
      these results suggest that narcissistic leaders can have positive effects on
      followers when their narcissism is tempered by humility.

PMID- 25621593
TI  - Retirees' motivational orientations and bridge employment: Testing the moderating
      role of gender.
AB  - Bridge employment refers to the labor force participation after people retire
      from career jobs. It is becoming a prevalent phenomenon for retirees
      transitioning from employment to complete work withdrawal. Building on existing
      literature on retirement transition and older adults' work motivation, the
      present study examined the effects of 3 motivational orientations (i.e., status
      striving, communion striving, and generativity striving) in relating to retirees'
      bridge employment participation (i.e., bridge employment status and bridge
      employment work hours). This study also applied the social gender role theory to
      examine the effect of gender in moderating the effects of motivational
      orientations. Data from 507 Chinese retirees in Beijing revealed that communion
      striving and generativity striving were positively related to bridge employment
      participation. Further, gender moderated the effect of status striving such that
      status striving was positively related to bridge employment participation for
      male retirees but not for female retirees. In addition, exploratory analysis was
      conducted to examine the effects of the same set of motivational orientations on
      postretirement volunteering activities. Results showed that status striving was
      negatively related to volunteering after retirement. The findings are discussed
      in terms of their theoretical implications for the bridge employment literature
      and practical implications for recruiting and retaining older workers.

PMID- 25621594
TI  - Light-powered tumbler movement of graphene oxide/polymer nanocomposites.
AB  - Photoresponsive lamina and flexible graphene oxide/polymer nanocomposite films
      were fabricated using a simple solution casting method. Fast, stable, and
      reversible photomechanical behavior of the nanocomposite films upon irradiation
      with visible light was observed based on the photothermal effect of graphene
      oxide and the shape memory effect of the polymer matrix. According to the
      principle of equilibrium apparatus, light-powered tumbler movement was achieved
      in these films by imitating the structure of a wobbly man. Although photodriven
      contraction, expansion, bending, twisting, oscillation, and cilia movement have
      been realized in photomechanical materials, novel forms of complicated motion are
      still a bottleneck problem limiting their practical applications. This work would
      have a significant impact on photomechanical materials in device applications for
      advanced functions. 

PMID- 25621596
TI  - From goals of care to improved family outcomes in the neonatal intensive care
      unit: determining the intervention.

PMID- 25621597
TI  - Drug-induced acute urinary retention #287.

PMID- 25621598
TI  - The importance of corn bread.

PMID- 25621599
TI  - A snapshot of the person within: using smartphone photos to understand values.

PMID- 25621600
TI  - Why interdisciplinary teams ten years later?

PMID- 25621602
TI  - A chronoamperometric screen printed carbon biosensor based on alkaline
      phosphatase inhibition for W(IV) determination in water, using 2-phospho-L
      ascorbic acid trisodium salt as a substrate.
AB  - This paper presents a chronoamperometric method to determine tungsten in water
      using screen-printed carbon electrodes modified with gold nanoparticles and cross
      linked alkaline phosphatase immobilized in the working electrode. Enzymatic
      activity over 2-phospho-l-ascorbic acid trisodium salt, used as substrate, was
      affected by tungsten ions, which resulted in a decrease of chronoamperometric
      current, when a potential of 200 mV was applied on 10 mM of substrate in a Tris
      HCl buffer pH 8.00 and 0.36 M of KCl. Calibration curves for the electrochemical
      method validation, give a reproducibility of 5.2% (n = 3), a repeatability of
      9.4% (n = 3) and a detection limit of 0.29 +/- 0.01 uM. Enriched tap water,
      purified laboratory water and bottled drinking water, with a certified tungsten
      reference solution traceable to NIST, gave a recovery of 97.1%, 99.1% and 99.1%
      respectively (n = 4 in each case) and a dynamic range from 0.6 to 30 uM. This
      study was performed by means of a Lineweaver-Burk plot, showing a mixed kinetic
      inhibition. 

PMID- 25621603
TI  - Eye/head tracking technology to improve HCI with iPad applications.
AB  - In order to improve human computer interaction (HCI) for people with special
      needs, this paper presents an alternative form of interaction, which uses the
      iPad's front camera and eye/head tracking technology. With this functional
      nature/capability operating in the background, the user can control already
      developed or new applications for the iPad by moving their eyes and/or head.
      There are many techniques, which are currently used to detect facial features,
      such as eyes or even the face itself. Open source bookstores exist for such
      purpose, such as OpenCV, which enable very reliable and accurate detection
      algorithms to be applied, such as Haar Cascade using very high-level programming.
      All processing is undertaken in real time, and it is therefore important to pay
      close attention to the use of limited resources (processing capacity) of devices,
      such as the iPad. The system was validated in tests involving 22 users of
      different ages and characteristics (people with dark and light-colored eyes and
      with/without glasses). These tests are performed to assess user/device
      interaction and to ascertain whether it works properly. The system obtained an
      accuracy of between 60% and 100% in the three test exercises taken into
      consideration. The results showed that the Haar Cascade had a significant effect
      by detecting faces in 100% of cases, unlike eyes and the pupil where interference
      (light and shade) evidenced less effectiveness. In addition to ascertaining the
      effectiveness of the system via these exercises, the demo application has also
      helped to show that user constraints need not affect the enjoyment and use of a
      particular type of technology. In short, the results obtained are encouraging and
      these systems may continue to be developed if extended and updated in the future.

PMID- 25621604
TI  - A multi-stage method for connecting participatory sensing and noise simulations.
AB  - Most simulation-based noise maps are important for official noise assessment but
      lack local noise characteristics. The main reasons for this lack of information
      are that official noise simulations only provide information about expected noise
      levels, which is limited by the use of large-scale monitoring of noise sources,
      and are updated infrequently. With the emergence of smart cities and ubiquitous
      sensing, the possible improvements enabled by sensing technologies provide the
      possibility to resolve this problem. This study proposed an integrated
      methodology to propel participatory sensing from its current random and
      distributed sampling origins to professional noise simulation. The aims of this
      study were to effectively organize the participatory noise data, to dynamically
      refine the granularity of the noise features on road segments (e.g., different
      portions of a road segment), and then to provide a reasonable spatio-temporal
      data foundation to support noise simulations, which can be of help to researchers
      in understanding how participatory sensing can play a role in smart cities. This
      study first discusses the potential limitations of the current participatory
      sensing and simulation-based official noise maps. Next, we explain how
      participatory noise data can contribute to a simulation-based noise map by
      providing (1) spatial matching of the participatory noise data to the virtual
      partitions at a more microscopic level of road networks; (2) multi-temporal scale
      noise estimations at the spatial level of virtual partitions; and (3) dynamic
      aggregation of virtual partitions by comparing the noise values at the relevant
      temporal scale to form a dynamic segmentation of each road segment to support
      multiple spatio-temporal noise simulations. In this case study, we demonstrate
      how this method could play a significant role in a simulation-based noise map.
      Together, these results demonstrate the potential benefits of participatory noise
      data as dynamic input sources for noise simulations on multiple spatio-temporal
      scales. 

PMID- 25621605
TI  - A compact 3D omnidirectional range sensor of high resolution for robust
      reconstruction of environments.
AB  - In this paper, an accurate range sensor for the three-dimensional reconstruction
      of environments is designed and developed. Following the principles of laser
      profilometry, the device exploits a set of optical transmitters able to project a
      laser line on the environment. A high-resolution and high-frame-rate camera
      assisted by a telecentric lens collects the laser light reflected by a parabolic
      mirror, whose shape is designed ad hoc to achieve a maximum measurement error of
      10 mm when the target is placed 3 m away from the laser source. Measurements are
      derived by means of an analytical model, whose parameters are estimated during a
      preliminary calibration phase. Geometrical parameters, analytical modeling and
      image processing steps are validated through several experiments, which indicate
      the capability of the proposed device to recover the shape of a target with high
      accuracy. Experimental measurements show Gaussian statistics, having standard
      deviation of 1.74 mm within the measurable range. Results prove that the
      presented range sensor is a good candidate for environmental inspections and
      measurements. 

PMID- 25621606
TI  - Preliminary study of a millimeter wave FMCW InSAR for UAS indoor navigation.
AB  - Small autonomous unmanned aerial systems (UAS) could be used for indoor
      inspection in emergency missions, such as damage assessment or the search for
      survivors in dangerous environments, e.g., power plants, underground railways,
      mines and industrial warehouses. Two basic functions are required to carry out
      these tasks, that is autonomous GPS-denied navigation with obstacle detection and
      high-resolution 3Dmapping with moving target detection. State-of-the-art sensors
      for UAS are very sensitive to environmental conditions and often fail in the case
      of poor visibility caused by dust, fog, smoke, flames or other factors that are
      met as nominal mission scenarios when operating indoors. This paper is a
      preliminary study concerning an innovative radar sensor based on the
      interferometric Synthetic Aperture Radar (SAR) principle, which has the potential
      to satisfy stringent requirements set by indoor autonomous operation. An
      architectural solution based on a frequency-modulated continuous wave (FMCW)
      scheme is proposed after a detailed analysis of existing compact and lightweight
      SAR. A preliminary system design is obtained, and the main imaging peculiarities
      of the novel sensor are discussed, demonstrating that high-resolution, high
      quality observation of an assigned control volume can be achieved. 

PMID- 25621607
TI  - Investigations on the impact of material-integrated sensors with the help of FEM
      based modeling.
AB  - We present investigations on the impact of material-integrated sensors with the
      help of finite element-based modeling. A sensor (inlay) integrated with a
      material (matrix) is always a foreign body in the material, which can lead to a
      "wound effect", that is degradation of the macroscopic behavior of a material. By
      analyzing the inlay's impact on the material in terms of mechanical load, heat
      conduction, stress during integration and other impacts of integration, this
      wound effect is analyzed. For the mechanical load, we found out that the inlay
      has to be at least as stretchable and bendable as the matrix. If there is a high
      thermal load during integration, the coefficients of the thermal expansion of the
      inlay have to be matched to the matrix. In the case of a high thermal load during
      operation, the inlay has to be as thin as possible or its thermal conductivity
      has to be adapted to the thermal conductivity of the matrix. To have a general
      view of things, the results are dimensionless and independent of the geometry. In
      each section, the results are illustrated by examples. Based on all of the
      results, we present our idea for the fabrication of future material-integrated
      sensors. 

PMID- 25621608
TI  - A high-throughput oxidative stress biosensor based on Escherichia coli roGFP2
      cells immobilized in a k-carrageenan matrix.
AB  - Biosensors fabricated with whole-cell bacteria appear to be suitable for
      detecting bioavailability and toxicity effects of the chemical(s) of concern, but
      they are usually reported to have drawbacks like long response times (ranging
      from hours to days), narrow dynamic range and instability during long term
      storage. Our aim is to fabricate a sensitive whole-cell oxidative stress
      biosensor which has improved properties that address the mentioned weaknesses. In
      this paper, we report a novel high-throughput whole-cell biosensor fabricated by
      immobilizing roGFP2 expressing Escherichia coli cells in a k-carrageenan matrix,
      for the detection of oxidative stress challenged by metalloid compounds. The E.
      coli roGFP2 oxidative stress biosensor shows high sensitivity towards arsenite
      and selenite, with wide linear range and low detection limit (arsenite: 1.0 * 10(
      3)-1.0 * 10(1) mg.L(-1), LOD: 2.0 * 10(-4) mg.L(-1); selenite: 1.0 * 10(-5)-1.0 *
      10(2) mg.L(-1), LOD: 5.8 * 10(-6) mg.L(-1)), short response times (0-9 min), high
      stability and reproducibility. This research is expected to provide a new
      direction in performing high-throughput environmental toxicity screening with
      living bacterial cells which is capable of measuring the bioavailability and
      toxicity of environmental stressors in a friction of a second.

PMID- 25621609
TI  - Cyber surveillance for flood disasters.
AB  - Regional heavy rainfall is usually caused by the influence of extreme weather
      conditions. Instant heavy rainfall often results in the flooding of rivers and
      the neighboring low-lying areas, which is responsible for a large number of
      casualties and considerable property loss. The existing precipitation forecast
      systems mostly focus on the analysis and forecast of large-scale areas but do not
      provide precise instant automatic monitoring and alert feedback for individual
      river areas and sections. Therefore, in this paper, we propose an easy method to
      automatically monitor the flood object of a specific area, based on the currently
      widely used remote cyber surveillance systems and image processing methods, in
      order to obtain instant flooding and waterlogging event feedback. The intrusion
      detection mode of these surveillance systems is used in this study, wherein a
      flood is considered a possible invasion object. Through the detection and
      verification of flood objects, automatic flood risk-level monitoring of specific
      individual river segments, as well as the automatic urban inundation detection,
      has become possible. The proposed method can better meet the practical needs of
      disaster prevention than the method of large-area forecasting. It also has
      several other advantages, such as flexibility in location selection, no
      requirement of a standard water-level ruler, and a relatively large field of
      view, when compared with the traditional water-level measurements using video
      screens. The results can offer prompt reference for appropriate disaster warning
      actions in small areas, making them more accurate and effective. 

PMID- 25621610
TI  - Pressure sensor via optical detection based on a 1D spin transition coordination
      polymer.
AB  - We have investigated the suitability of using the 1D spin crossover coordination
      polymer [Fe(4-(2'-hydroxyethyl)-1,2,4-triazole)3]I2?H2O, known to crossover
      around room temperature, as a pressure sensor via optical detection using various
      contact pressures up to 250 MPa. A dramatic persistent colour change is observed.
      The experimental data, obtained by calorimetric and Mossbauer measurements, have
      been used for a theoretical analysis, in the framework of the Ising-like model,
      of the thermal and pressure induced spin state switching. The pressure (P)
      temperature (T) phase diagram calculated for this compound has been used to
      obtain the P-T bistability region. 

PMID- 25621611
TI  - Validation of a CFD model by using 3D sonic anemometers to analyse the air
      velocity generated by an air-assisted sprayer equipped with two axial fans.
AB  - A computational fluid dynamics (CFD) model of the air flow generated by an air
      assisted sprayer equipped with two axial fans was developed and validated by
      practical experiments in the laboratory. The CFD model was developed by
      considering the total air flow supplied by the sprayer fan to be the main
      parameter, rather than the outlet air velocity. The model was developed for three
      air flows corresponding to three fan blade settings and assuming that the sprayer
      is stationary. Actual measurements of the air velocity near the sprayer were
      taken using 3D sonic anemometers. The workspace sprayer was divided into three
      sections, and the air velocity was measured in each section on both sides of the
      machine at a horizontal distance of 1.5, 2.5, and 3.5 m from the machine, and at
      heights of 1, 2, 3, and 4 m above the ground The coefficient of determination
      (R2) between the simulated and measured values was 0.859, which demonstrates a
      good correlation between the simulated and measured data. Considering the overall
      data, the air velocity values produced by the CFD model were not significantly
      different from the measured values. 

PMID- 25621612
TI  - A non-uniformly under-sampled blade tip-timing signal reconstruction method for
      blade vibration monitoring.
AB  - High-speed blades are often prone to fatigue due to severe blade vibrations. In
      particular, synchronous vibrations can cause irreversible damages to the blade.
      Blade tip-timing methods (BTT) have become a promising way to monitor blade
      vibrations. However, synchronous vibrations are unsuitably monitored by uniform
      BTT sampling. Therefore, non-equally mounted probes have been used, which will
      result in the non-uniformity of the sampling signal. Since under-sampling is an
      intrinsic drawback of BTT methods, how to analyze non-uniformly under-sampled BTT
      signals is a big challenge. In this paper, a novel reconstruction method for non
      uniformly under-sampled BTT data is presented. The method is based on the
      periodically non-uniform sampling theorem. Firstly, a mathematical model of a non
      uniform BTT sampling process is built. It can be treated as the sum of certain
      uniform sample streams. For each stream, an interpolating function is required to
      prevent aliasing in the reconstructed signal. Secondly, simultaneous equations of
      all interpolating functions in each sub-band are built and corresponding
      solutions are ultimately derived to remove unwanted replicas of the original
      signal caused by the sampling, which may overlay the original signal. In the end,
      numerical simulations and experiments are carried out to validate the feasibility
      of the proposed method. The results demonstrate the accuracy of the reconstructed
      signal depends on the sampling frequency, the blade vibration frequency, the
      blade vibration bandwidth, the probe static offset and the number of samples. In
      practice, both types of blade vibration signals can be particularly reconstructed
      by non-uniform BTT data acquired from only two probes. 

PMID- 25621613
TI  - A 3D microfluidic chip for electrochemical detection of hydrolysed nucleic bases
      by a modified glassy carbon electrode.
AB  - Modification of carbon materials, especially graphene-based materials, has wide
      applications in electrochemical detection such as electrochemical lab-on-chip
      devices. A glassy carbon electrode (GCE) modified with chemically alternated
      graphene oxide was used as a working electrode (glassy carbon modified by
      graphene oxide with sulphur containing compounds and Nafion) for detection of
      nucleobases in hydrolysed samples (HCl pH = 2.9, 100  degrees C, 1 h,
      neutralization by NaOH). It was found out that modification, especially with
      trithiocyanuric acid, increased the sensitivity of detection in comparison with
      pure GCE. All processes were finally implemented in a microfluidic chip formed
      with a 3D printer by fused deposition modelling technology. As a material for
      chip fabrication, acrylonitrile butadiene styrene was chosen because of its
      mechanical and chemical stability. The chip contained the one chamber for the
      hydrolysis of the nucleic acid and another for the electrochemical detection by
      the modified GCE. This chamber was fabricated to allow for replacement of the
      GCE. 

PMID- 25621614
TI  - Analysis of frequency response and scale-factor of tuning fork micro-gyroscope
      operating at atmospheric pressure.
AB  - This paper presents a study of the frequency response and the scale-factor of a
      tuning fork micro-gyroscope operating at atmospheric pressure in the presence of
      an interference sense mode by utilizing the approximate transfer function. The
      optimal demodulation phase (ODP), which is always ignored in vacuum packaged
      micro-gyroscopes but quite important in gyroscopes operating at atmospheric
      pressure, is obtained through the transfer function of the sense mode, including
      the primary mode and the interference mode. The approximate transfer function of
      the micro-gyroscope is deduced in consideration of the interference mode and the
      ODP. Then, the equation describing the scale-factor of the gyroscope is also
      obtained. The impacts of the interference mode and Q-factor on the frequency
      response and the scale-factor of the gyroscope are analyzed through numerical
      simulations. The relationship between the scale-factor and the demodulation phase
      is also illustrated and gives an effective way to find out the ODP in practice.
      The simulation results predicted by the transfer functions are in close agreement
      with the results of the experiments. The analyses and simulations can provide
      constructive guidance on bandwidth and sensitivity designs of the micro
      gyroscopes operating at atmospheric pressure. 

PMID- 25621617
TI  - Detection of Aspergillus flavus in stored peanuts using real-time PCR and the
      expression of aflatoxin genes in toxigenic and atoxigenic A. flavus isolates.
AB  - Aspergillus flavus is the main species from section Flavi responsible for
      aflatoxin accumulation in stored peanuts. Rapid methods to detect A. flavus could
      help to prevent aflatoxins from entering the food chain. A real-time polymerase
      chain reaction (RTi-PCR) assay was standardized for rapid, specific, and
      sensitive detection of A. flavus in stored peanuts. A. flavus was detected in
      53.6% and 50% of peanut samples by RTi-PCR and A. flavus and Aspergillus
      parasiticus agar culture, respectively, with 95% agreement between them. Twenty
      two A. flavus isolates were screened using high-performance liquid chromatography
      for their capacity to produce aflatoxin AFB1 (B1). B1 was produced by >72% of the
      isolates. Sixteen isolates produced B1 at concentrations ranging from 1.64 to
      109.18 MUg/mL. Four aflatoxin biosynthetic pathway genes (aflD, aflM, aflP, and
      aflQ) were evaluated using PCR and reverse-transcription PCR in 22 A. flavus
      isolates from peanut kernels with the aim of rapidly and accurately
      differentiating toxigenic and atoxigenic isolates. The PCR amplification of genes
      did not correlate with aflatoxin production capability. The expression of aflD
      and aflQ was a good marker for differentiating toxigenic from atoxigenic
      isolates.

PMID- 25621616
TI  - Cleavage efficient 2A peptides for high level monoclonal antibody expression in
      CHO cells.
AB  - Linking the heavy chain (HC) and light chain (LC) genes required for monoclonal
      antibodies (mAb) production on a single cassette using 2A peptides allows control
      of LC and HC ratio and reduces non-expressing cells. Four 2A peptides derived
      from the foot-and-mouth disease virus (F2A), equine rhinitis A virus (E2A),
      porcine teschovirus-1 (P2A) and Thosea asigna virus (T2A), respectively, were
      compared for expression of 3 biosimilar IgG1 mAbs in Chinese hamster ovary (CHO)
      cell lines. HC and LC were linked by different 2A peptides both in the absence
      and presence of GSG linkers. Insertion of a furin recognition site upstream of 2A
      allowed removal of 2A residues that would otherwise be attached to the HC.
      Different 2A peptides exhibited different cleavage efficiencies that correlated
      to the mAb expression level. The relative cleavage efficiency of each 2A peptide
      remains similar for expression of different IgG1 mAbs in different CHO cells.
      While complete cleavage was not observed for any of the 2A peptides, GSG linkers
      did enhance the cleavage efficiency and thus the mAb expression level. T2A with
      the GSG linker (GT2A) exhibited the highest cleavage efficiency and mAb
      expression level. Stably amplified CHO DG44 pools generated using GT2A had titers
      357, 416 and 600 mg/L for the 3 mAbs in shake flask batch cultures. Incomplete
      cleavage likely resulted in incorrectly processed mAb species and aggregates,
      which were removed with a chromatin-directed clarification method and protein A
      purification. The vector and methods presented provide an easy process beneficial
      for both mAb development and manufacturing. 

PMID- 25621618
TI  - Acidity of the amidoxime functional group in aqueous solution: a combined
      experimental and computational study.
AB  - Poly(acrylamidoxime) adsorbents are often invoked in discussions of mining
      uranium from seawater. While the amidoxime-uranyl chelation mode has been
      established, a number of essential binding constants remain unclear. This is
      largely due to the wide range of conflicting pK(a) values that have been reported
      for the amidoxime functional group. To resolve this existing controversy we
      investigated the pK(a) values of the amidoxime functional group using a
      combination of experimental and computational methods. Experimentally, we used
      spectroscopic titrations to measure the pK(a) values of representative
      amidoximes, acetamidoxime, and benzamidoxime. Computationally, we report on the
      performance of several protocols for predicting the pK(a) values of aqueous
      oxoacids. Calculations carried out at the MP2 or M06-2X levels of theory combined
      with solvent effects calculated using the SMD model provide the best overall
      performance, with a root-mean-square deviation of 0.46 pK(a) units and 0.45 pK(a)
      units, respectively. Finally, we employ our two best methods to predict the pK(a)
      values of promising, uncharacterized amidoxime ligands, which provides a
      convenient means for screening suitable amidoxime monomers for future generations
      of poly(acrylamidoxime) adsorbents.

PMID- 25621619
TI  - Exploiting the power of OMICS approaches to produce E. coli O157 vaccines.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains are well-documented human
      pathogens and causative agents of diarrheal episodes and hemorrhagic colitis. The
      serotype O157:H7 is highly virulent and responsible for both outbreaks and
      sporadic cases of diarrhea. Because antibiotic treatment is contraindicated
      against this pathogen, development of a human vaccine could be an effective
      intervention in public health. In our recent Infection and Immunity paper, we
      applied integrated approaches of in silico genome wide search combined with
      bioinformatics tools to identify and test O157 vaccine candidates for their
      protective effect on a murine model of gastrointestinal infection. Using
      genomic/immunoinformatic approaches that are further described here, we
      categorized vaccine candidates as high, medium, and low priorities, and
      demonstrate that some high priority candidates were able to significantly induce
      Th2 cytokines and reduce EHEC colonization. Using the STRING database, we have
      recently evaluated the vaccine candidates and predict functional protein
      interactions, determining whether correlations exist for the development of a
      multi-subunit vaccine, targeting different pathways against EHEC O157:H7. The
      overall approach is designed to screen potential vaccine candidates against EHEC;
      however, the methodology can be quickly applied to many other intestinal
      pathogens. 

PMID- 25621621
TI  - What about E-cigarettes?

PMID- 25621620
TI  - Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio
      cholerae spatial cues within the small intestine.
AB  - The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in
      response to environmental stimuli to enable bacteria to transition between
      different lifestyles. Here we discuss our recent findings that the human pathogen
      Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to
      regulate intracellular c-di-GMP. We have demonstrated that bile acids increase
      intracellular c-di-GMP to promote biofilm formation. We have also shown that this
      bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and
      that this interaction is dependent on pH, suggesting that V. cholerae uses these
      2 environmental cues to sense and adapt to its relative location in the small
      intestine. Increased intracellular c-di-GMP by bile is attributed to increased c
      di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one
      phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by
      which bile controls the activity of the 3 DGCs and the regulators of bile
      mediated transcriptional repression of the PDE are not yet known. Moreover, the
      impact of varying concentrations of bile and bicarbonate at different locations
      within the small intestine and the response of V. cholerae to these cues remains
      unclear. The native microbiome and pharmaceuticals, such as omeprazole, can
      impact bile and pH within the small intestine, suggesting these are potential
      unappreciated factors that may alter V. cholerae pathogenesis. 

PMID- 25621622
TI  - A 2-year-old male with persistent fever and pneumonia.

PMID- 25621623
TI  - An 8-year-old male with generalized itchy and scaly rash for 3 weeks.

PMID- 25621625
TI  - Common signs and symptoms and unusual diagnoses: part 1.

PMID- 25621624
TI  - A 14-year-old female with difficulty swallowing.

PMID- 25621626
TI  - Medically complex children and early intervention for comprehensive medical care
      at home.
AB  - We present the case of a 4-year-old with multiple congenital anomalies. These
      included complete tracheal rings with agenesis of the right lung and missing
      right ribs. He was hospitalized from birth until he was age 3 years and 6 months.
      At age 4 years and 4 months he had yet to move to a family home or experience his
      first day of school because he was in a transitional care facility. The intensity
      of his care was initially high, slowly declined over time, and eventually entered
      the range where he would be potentially manageable in a home environment. Despite
      the countless medical teams treating him, he did not receive a referral either to
      the early intervention or educational services that he had a right to under the
      Individuals with Disabilities Education Act. While his case is extreme, there is
      a disconnect between the United States health care and educational systems, which
      negatively impacts both the health and development of children with chronic
      conditions who require frequent and prolonged hospitalizations.

PMID- 25621627
TI  - A neonate with a vesiculopustular rash.
AB  - Transient myeloproliferative disorder (TMD) is a unique form of acute
      megakaryocytic leukemia (AMKL) that spontaneously regresses and is found in 3% to
      10% of neonates with Down syndrome (DS). We report the case of a neonate with DS
      who presented with a widespread vesiculopustular eruption as an initial sign of
      TMD. Complete blood count was normal but peripheral smear revealed circulating
      megakaryoblasts. The severity of skin lesions correlated with the blast count. By
      age 2 months the TMD resolved and the patient remains disease-free after 18
      months of follow-up. Several important features of TMD are highlighted: skin
      findings may provide an important clinical clue to TMD diagnosis; manual review
      of the peripheral smear is necessary when TMD is suspected; and patients with a
      history of TMD have a very high (~30%) risk of recurrence with a persistent AMKL
      within the first 3 years of life.

PMID- 25621628
TI  - A 9-year-old male with hypertension.
AB  - Blood pressure screening is an important component of the pediatric outpatient
      visit. The following case describes a 9-year-old male with a medical history
      significant for prematurity, obesity, asthma, and secondary nighttime enuresis
      who was admitted to our institution with hypertensive urgency. His blood pressure
      on presentation was 166/122 mm Hg, and he was clinically asymptomatic. There is a
      strong family history of hypertension, renal disease, and brain cancer. During
      his admission, his blood pressures were medically managed. He received a
      comprehensive diagnostic investigation of possible primary or secondary causes of
      hypertension, including consultation with nephrology, endocrinology, and
      ophthalmology subspecialty teams. The etiology of the hypertension was
      determined, and he was subsequently treated for a rare and life-threatening
      disease. This case highlights the importance of the close surveillance of
      children with hypertension.

PMID- 25621629
TI  - An adolescent girl with Crohn's disease, fever, and sore throat.
AB  - An adolescent female with a past medical history significant for Crohn's disease
      presented with fevers, tonsillitis without exudate, and tender posterior cervical
      lymphadenopathy. Laboratory results showed transaminitis, leukocytosis with a
      left shift, and atypical lymphocytes on a blood smear. The patient did not
      respond to supportive care or dexamethasone, necessitating a tonsillectomy and
      adenoidectomy. Although her presentation was consistent with infectious
      mononucleosis, diagnosis was not confirmed until Epstein-Barr virus (EBV)
      polymerase chain reaction (PCR) from tonsillar tissue was positive. False
      negative results on the heterophile antibody test are common in pediatric
      populations and the detection of EBV antibodies is further complicated in
      immunocompromised patients. Studies indicate PCR is a more sensitive test,
      although there is no consensus regarding ideal material to use or quantitative
      levels necessitating intervention.

PMID- 25621630
TI  - A 3-year-old female with abdominal pain, vomiting, and an abdominal mass.
AB  - We present a case of a 3-year-old female with a 10-day history of lower abdominal
      pain, distention, and vomiting, as well as fatigue, low-grade fever, and
      subjective weight loss who was found to have utero-ovarian torsion with pathology
      revealing hemorrhagic and infarcted tissue. While the literature is limited, it
      suggests that utero-adnexal torsion in children may be more common than
      previously recognized. A missed, or even delayed, diagnosis of utero-adnexal
      torsion has the potential to result in irreversible ischemic damage. Utero
      adnexal torsion should therefore be included in the differential diagnosis for
      girls presenting with acute abdominopelvic pain. Pelvic ultrasound to evaluate
      the uterus and adnexae is an important non-invasive first step in establishing
      the diagnosis. Computed tomography scan or magnetic resonance imaging can be
      considered in the case of indeterminate ultrasound. The diagnosis of utero
      adnexal torsion must be made early, and surgical intervention must be timely in
      order to preserve fertility.

PMID- 25621631
TI  - Problematic Online Pornography Use: A Media Attendance Perspective.
AB  - Since the rise of the popularity of the Internet, the accessibility of
      pornography has been a growing concern. One particular concern is the potential
      risk for addictive behaviors to occur as a result of the ease of viewing online
      pornographic material. The research presented herein explored online pornography
      addiction using a media attendance perspective, which allows media critics to
      examine the needs that people seek to fulfill from engaging with various media.
      Past studies that have used a media attendance perspective to explore media
      addiction, rephrased here as problematic media use, have done so using social
      cognitive theory and the concept of deficient self-regulation. Deficient self
      regulation may be experienced by all media consumers and can range from normally
      impulsive media choices to pathological media choices which may result in
      detrimental life consequences. Borrowing from this, the current study reevaluated
      online pornography addiction using deficient self-regulation within a
      sociocognitive framework of media attendance. Results of our model show deficient
      self-regulation influences habitual online pornography consumption. Moreover,
      online pornography use motivated by social needs is perpetuated by deficient self
      regulation and may lead to negative life consequences in some individuals. These
      findings contribute a new perspective and framework for understanding problematic
      online pornography use.

PMID- 25621632
TI  - Epigenetic-mediated reprogramming of pancreatic endocrine cells.
AB  - SIGNIFICANCE: Type 1 diabetes (T1D) results from cell-mediated autoimmune
      destruction of insulin-secreting pancreatic beta cells (beta-cells). In the
      context of T1D, the scarcity of organ donors has driven research to alternate
      sources of functionally competent, insulin-secreting beta-cells as substitute for
      donor islets to meet the clinical need for transplantation therapy. RECENT
      ADVANCES: Experimental evidence of an inherent plasticity of pancreatic cells has
      fuelled interest in in vivo regeneration of beta-cells. Transcriptional
      modulation and direct reprogramming of noninsulin secreting pancreatic alpha
      cells to functionally mimic insulin-secreting beta-cells is one of the promising
      avenues to the treatment of diabetes. Recent studies now show that adult
      progenitor and glucagon(+) alpha-cells can be converted into beta-like cells in
      vivo, as a result of specific activation of the Pax4 gene in alpha-cells and
      curing diabetes in preclinical models. CRITICAL ISSUES: The challenge now is to
      understand the precise developmental transitions mediated by endocrine
      transcription factors and co-regulatory determinants responsible for pancreatic
      function and repair. FUTURE DIRECTIONS: Epigenetic-mediated regulation of
      transcription factor binding in pancreatic alpha-cells by specific drugs to
      direct reprogramming into functional insulin producing cells could be of
      potential innovative therapy for the treatment of T1D.

PMID- 25621634
TI  - Bendable, free-standing calcite thin films.
AB  - Since the hardness and toughness of natural nacre are determined by hierarchical
      microstructures with organic matters, it is of great importance to control the
      microstructures of artificial free-standing CaCO3 thin films. However, the
      fabrication of such films has so far been quite limited, to the extent that their
      mechanical properties have not been reported. To address this, free-standing
      calcite thin films were prepared through repeated cycles of layer-by-layer
      deposition of vaterite precursor composite particles with organic polymers,
      followed by a phase transition to calcite. In this way, two distinct calcite thin
      film types were produced based on either 3.2 or 1.0 wt % organic material, with
      subsequent three-point bending tests revealing that both exhibit elastic bending
      prior to fracture. More importantly, by increasing the organic content from 1.0
      to 3.2 wt %, the bending strength increased from 0.95 +/- 0.26 MPa to 1.90 +/-
      0.21 MPa. 

PMID- 25621635
TI  - Message hits home.

PMID- 25621636
TI  - On recalls.

PMID- 25621639
TI  - Ten questions with .... Eleanor Sherman.

PMID- 25621640
TI  - What is the biggest healthcare technology challenge you see on the horizon for
      2015?

PMID- 25621643
TI  - Hello, partner: how working with nurses makes for better healthcare technology.

PMID- 25621644
TI  - Certification: a rewarding endeavor.

PMID- 25621645
TI  - Back to basics and thriving at VA's CE departments.

PMID- 25621646
TI  - A roundtable discussion: trends, tasks, and challenges in imaging.

PMID- 25621648
TI  - Saving lives, saving families: continuous monitoring for patients on opioids.

PMID- 25621649
TI  - A science-based approach to testing product quality.

PMID- 25621650
TI  - Wireless healthcare FAQs: prepurchase and regulatory issues to consider.

PMID- 25621651
TI  - DeSalvo: health IT is 'more than just EHRs'.

PMID- 25621652
TI  - Patient safety and healthcare technology management.

PMID- 25621653
TI  - Electrode errors frustrate users.

PMID- 25621655
TI  - Prepare to be taken over.

PMID- 25621656
TI  - HTM levels guide offers more than meets the eye.

PMID- 25621658
TI  - Pathobiology of transfusion reactions.
AB  - Antibody-induced hemolytic transfusion reactions were first described over 300
      years ago. Indeed, during its early evolution, transfusion medicine focused
      almost exclusively on issues in immunohematology to prevent such events. However,
      despite the best of efforts to avoid them, incompatible transfusions still occur,
      through both error and an inability to obtain compatible red blood cells for
      patients who are alloimmunized against multiple antigens. Because transfusing
      units of incompatible blood is potentially lethal, studies on human volunteers
      are not ethical. Thus, understanding of hemolytic transfusion reactions is
      generated through clinical cases, animal models, inference from related human
      pathologies, or studies using small volumes of transfused red blood cells. Over
      the past several decades, substantial new knowledge has been accumulated
      regarding the mechanisms of hemolysis, the metabolism of products of hemolysis,
      and the effects of both on recipient biology. Using these data sources, this
      article traces the historical generation of this knowledge and describes recent
      advances. 

PMID- 25621659
TI  - The emerging picture of autism spectrum disorder: genetics and pathology.
AB  - Autism spectrum disorder (ASD) is defined by impaired social interaction and
      communication accompanied by stereotyped behaviors and restricted interests.
      Although ASD is common, its genetic and clinical features are highly
      heterogeneous. A number of recent breakthroughs have dramatically advanced our
      understanding of ASD from the standpoint of human genetics and neuropathology.
      These studies highlight the period of fetal development and the processes of
      chromatin structure, synaptic function, and neuron-glial signaling. The initial
      efforts to systematically integrate findings of multiple levels of genomic data
      and studies of mouse models have yielded new clues regarding ASD pathophysiology.
      This early work points to an emerging convergence of disease mechanisms in this
      complex and etiologically heterogeneous disorder. 

PMID- 25621660
TI  - Engineered in vitro disease models.
AB  - The ultimate goal of most biomedical research is to gain greater insight into
      mechanisms of human disease or to develop new and improved therapies or
      diagnostics. Although great advances have been made in terms of developing
      disease models in animals, such as transgenic mice, many of these models fail to
      faithfully recapitulate the human condition. In addition, it is difficult to
      identify critical cellular and molecular contributors to disease or to vary them
      independently in whole-animal models. This challenge has attracted the interest
      of engineers, who have begun to collaborate with biologists to leverage recent
      advances in tissue engineering and microfabrication to develop novel in vitro
      models of disease. As these models are synthetic systems, specific molecular
      factors and individual cell types, including parenchymal cells, vascular cells,
      and immune cells, can be varied independently while simultaneously measuring
      system-level responses in real time. In this article, we provide some examples of
      these efforts, including engineered models of diseases of the heart, lung,
      intestine, liver, kidney, cartilage, skin and vascular, endocrine,
      musculoskeletal, and nervous systems, as well as models of infectious diseases
      and cancer. We also describe how engineered in vitro models can be combined with
      human inducible pluripotent stem cells to enable new insights into a broad
      variety of disease mechanisms, as well as provide a test bed for screening new
      therapies. 

PMID- 25621661
TI  - Diseases of pulmonary surfactant homeostasis.
AB  - Advances in physiology and biochemistry have provided fundamental insights into
      the role of pulmonary surfactant in the pathogenesis and treatment of preterm
      infants with respiratory distress syndrome. Identification of the surfactant
      proteins, lipid transporters, and transcriptional networks regulating their
      expression has provided the tools and insights needed to discern the molecular
      and cellular processes regulating the production and function of pulmonary
      surfactant prior to and after birth. Mutations in genes regulating surfactant
      homeostasis have been associated with severe lung disease in neonates and older
      infants. Biophysical and transgenic mouse models have provided insight into the
      mechanisms underlying surfactant protein and alveolar homeostasis. These studies
      have provided the framework for understanding the structure and function of
      pulmonary surfactant, which has informed understanding of the pathogenesis of
      diverse pulmonary disorders previously considered idiopathic. This review
      considers the pulmonary surfactant system and the genetic causes of acute and
      chronic lung disease caused by disruption of alveolar homeostasis. 

PMID- 25621662
TI  - DNA replication stress as a hallmark of cancer.
AB  - Human cancers share properties referred to as hallmarks, among which sustained
      proliferation, escape from apoptosis, and genomic instability are the most
      pervasive. The sustained proliferation hallmark can be explained by mutations in
      oncogenes and tumor suppressors that regulate cell growth, whereas the escape
      from apoptosis hallmark can be explained by mutations in the TP53, ATM, or MDM2
      genes. A model to explain the presence of the three hallmarks listed above, as
      well as the patterns of genomic instability observed in human cancers, proposes
      that the genes driving cell proliferation induce DNA replication stress, which,
      in turn, generates genomic instability and selects for escape from apoptosis.
      Here, we review the data that support this model, as well as the mechanisms by
      which oncogenes induce replication stress. Further, we argue that DNA replication
      stress should be considered as a hallmark of cancer because it likely drives
      cancer development and is very prevalent. 

PMID- 25621664
TI  - Genetics and epigenetics of human retinoblastoma.
AB  - Retinoblastoma is a pediatric tumor of the developing retina from which the
      genetic basis for cancer development was first described. Inactivation of both
      copies of the RB1 gene is the predominant initiating genetic lesion in
      retinoblastoma and is rate limiting for tumorigenesis. Recent whole-genome
      sequencing of retinoblastoma uncovered a tumor that had no coding-region
      mutations or focal chromosomal lesions other than in the RB1 gene, shifting the
      paradigm in the field. The retinoblastoma genome can be very stable; therefore,
      epigenetic deregulation of tumor-promoting pathways is required for
      tumorigenesis. This review highlights the genetic and epigenetic changes in
      retinoblastoma that have been reported, with special emphasis on recent whole
      genome sequencing and epigenetic analyses that have identified novel candidate
      genes as potential therapeutic targets. 

PMID- 25621665
TI  - Bilingual memory representations in less fluent Chinese-English bilinguals: an
      event-related potential study.
AB  - The present study was designed to investigate bilingual memory representations in
      less fluent Chinese-English bilinguals and the effect of word familiarity on
      bilingual memory representations with a translation priming paradigm and the
      event-related potential (ERP) technique. Three factors (translation order, word
      familiarity, and repetition status) were manipulated in this study, and the major
      dependent variable was the magnitude of the N400 repetition effect, which is
      related to semantic expectation and is an important physiological index of
      language processing. The results confirmed the asymmetry in bilingual memory with
      stronger L2-LI links compared to L1-L2 links in less fluent Chinese-English
      bilinguals, and that word familiarity was an important factor in the memory
      representations of these less fluent bilinguals.

PMID- 25621666
TI  - Entrepreneurial stressors as predictors of entrepreneurial burnout.
AB  - Research on the effects of entrepreneurial stressors is limited, especially
      regarding its relation to the burnout that frequently occurs in the process of
      starting and growing a venture. The effect of the role of entrepreneurial
      stressors (workload, competitive comparison, demands-of-knowledge, managing
      responsibility, and resource requirements) on burnout (emotional exhaustion,
      depersonalization, and reduced personal accomplishment) was examined in a Chinese
      sample of entrepreneurs. Entrepreneurial stressors emerged as a significant
      predictor of burnout in the process of entrepreneurship in a sample of 289
      entrepreneurs (63.8% men; M age = 26.2 yr.; 39.6% of their parents have been self
      employed). The findings clarify the functional relationship between
      entrepreneurial stressors and burnout. Entrepreneurial stressors played multiple
      roles. Managing responsibility was an active contributor to the sense of
      achievement and to emotional exhaustion. Workload was an active contributor to
      emotional exhaustion. Demands-of-knowledge negatively affected three of the
      dimensions of burnout. Theoretical and practical implications for management of
      the effect of these relationships are discussed.

PMID- 25621667
TI  - Caregiving representations at work and the moderating role of job self-efficacy.
AB  - This study measured the effect of job self-efficacy and caregiving dimensions
      (hyperactivation and deactivation) on Organizational Citizenship Behavior (OCB)
      in a sample of 160 customer service workers. While job self-efficacy and
      caregiving deactivation independently had moderate main effects on OCB-Individual
      and OCB-Organizational, the effect of caregiving hyperactivation was smaller and
      significantly contributed solely to OCB-Organizational. When caregiving
      dimensions were examined in interaction with job self-efficacy, the effect of
      deactivated caregiving on OCB-Organizational was stronger for workers who scored
      high on job self-efficacy.

PMID- 25621668
TI  - Influence of culture on tripartite self-concept development in adolescence: a
      comparison between Han and Uyghur cultures.
AB  - This study investigated the development of cultural variability in interdependent
      self-construal by comparing the differences in the tripartite self-concept of
      adolescent samples from the Han and Uyghur cultures. Participants (460 males, 522
      females; M age = 16.3 yr., SD = 4.8) in the sub-phases of pre-, early-, mid-,
      late- and post-adolescence were asked to completed the revised Twenty Statements
      Test, and the items generated by the participants were coded into private,
      relational, and collective self-statements. The private self-statements were
      further differentiated by personal and social orientation, and the relational
      self-statements were further coded into family and friend focus. The relational
      aspect of an individual's self, or personal relationship, became increasingly
      important with age in the Han cultural groups, whereas the collective aspect of
      an individual's self, or social identity, became increasingly important with age
      in the Uyghur cultural groups. These findings seem to show the development of
      differences between relational and collective interdependent self-construals.
      Furthermore, these findings emphasize the need for further research into the
      development of within-cultural differences in self-construal.

PMID- 25621669
TI  - Validation of the Italian translation of the affective neuroscience personality
      scales.
AB  - The theoretical perspective on affective neuroscience advanced by Panksepp,
      identified six basic innate affective systems: the SEEK, FEAR, ANGER, SADNESS,
      PLAY, and CARE systems. (3) It has been proposed that the fundamental elements of
      human personality and its variants may be based on the different expressions of
      these basic emotional systems and their combinations. A self-report inventory,
      the Affective Neuroscience Personality Scales (ANPS), has been devised with the
      aim of studying and evaluating personality from this perspective. This study
      reports data on the initial validation of ANPS Italian translation on a sample of
      418 adult participants. Descriptive statistics for each scale were calculated,
      assessing also their internal consistency, as a measure of reliability and
      factorial validity. Acceptable internal consistency was found in all but one
      scale (SADNESS), and a second-order factor analysis identified a more general
      affective feature of personality hinging on relational characteristics,
      independent of the dimensions of general positive and negative affect.

PMID- 25621670
TI  - Confidence: a critical review of the literature and an alternative perspective
      for general and specific self-confidence.
AB  - This article provides a critical review of the literature pertaining to self
      confidence and advances the argument of the need to separate the construct into
      its general and specific domains. The rationale is that distinguishing self
      confidence into general and specific will increase conceptual parsimony and
      predictive power of each construct.

PMID- 25621671
TI  - Places for help: micro-level variation in helping behavior toward a stranger.
AB  - A field experiment was conducted to explore whether certain urban places have an
      influence on helpfulness. Places semantically associated with the idea of love
      may act as primes and trigger increased helpfulness. Passersby (96 men, 96 women)
      happened upon a female confederate with a "leg injury" who inadvertently dropped
      personal items. The experiment took place in a common street or near a hospital
      entrance, a Catholic church, or a flower shop. Results indicated that helpfulness
      increased near a hospital or flower shop. These results are explained in light of
      automatic activation of normative behavior.

PMID- 25621663
TI  - Protein glycosylation in cancer.
AB  - Neoplastic transformation results in a wide variety of cellular alterations that
      impact the growth, survival, and general behavior of affected tissue. Although
      genetic alterations underpin the development of neoplastic disease, epigenetic
      changes can exert an equally significant effect on neoplastic transformation.
      Among neoplasia-associated epigenetic alterations, changes in cellular
      glycosylation have recently received attention as a key component of neoplastic
      progression. Alterations in glycosylation appear to not only directly impact cell
      growth and survival but also facilitate tumor-induced immunomodulation and
      eventual metastasis. Many of these changes may support neoplastic progression,
      and unique alterations in tumor-associated glycosylation may also serve as a
      distinct feature of cancer cells and therefore provide novel diagnostic and even
      therapeutic targets. 

PMID- 25621672
TI  - Examining relations between locus of control, loneliness, subjective well-being,
      and preference for online social interaction.
AB  - The unprecedented popularity of online communication has raised interests and
      concerns among the public as well as in scholarly circles. Online communications
      have pushed people farther away from one another. This study is a further
      examination of the effects of online communications on well-being, in particular:
      Locus of control, Loneliness, Subjective well-being, and Preference for online
      social interaction. Chinese undergraduate students (N = 260; 84 men, 176 women; M
      age = 20.1 yr., SD = 1.2) were questioned about demographic information and use
      of social media as well as four previously validated questionnaires related to
      well-being. Most participants used QQ, a popular social networking program, as
      the major channel for online social interactions. Locus of control was positively
      related to Loneliness and Preference for online social interaction, but
      negatively related to Subjective well-being; Loneliness (positively) and
      Subjective well-being (negatively) were related to Preference for online social
      interaction; and Loneliness and Subjective well-being had a full mediating effect
      between the relationships of Locus of control and Preference for online social
      interaction. The findings of the study showed that more lonely, unhappy, and
      externally controlled students were more likely to be engaged in online social
      interaction. Improving students' locus of control, loneliness, and happiness may
      help reduce problematic Internet use.

PMID- 25621673
TI  - Social competence: evaluation of assertiveness in Spanish adolescents.
AB  - Relations between assertiveness in adolescents' social behavior and demographic
      variables were assessed in 4,943 Spanish adolescents, ages 12 to 17 years,
      enrolled in 32 schools for Compulsory Secondary Education. Province of residence,
      school size, age, grade, and academic focus were statistically significant
      sources of variance in assertiveness scores. All effects were small. Patterns in
      responses indicate the items should be reviewed to improve the measure for
      adolescents, and as a tool for addressing teens' social competence in real life
      situations.

PMID- 25621674
TI  - Paranormal beliefs of Latvian college students: a Latvian version of the revised
      paranormal belief scale.
AB  - A Latvian version of the Revised Paranormal Belief Scale (RPBS) was completed by
      229 Latvian university students. Exploratory and confirmatory factor analyses
      revealed six relatively independent factors labeled Magical Abilities,
      Psychokinesis, Traditional Religious Belief, Superstition, Spirit Travel, and
      Extraordinary Life Forms. Based on the motivational-control model, it was
      hypothesized that the societal stressors affecting Latvian society during the
      last 50 yr. have led to a reduced sense of personal control which, in turn, has
      resulted in increased endorsement of paranormal beliefs to re-establish a sense
      of control. The motivational-control hypothesis was not supported. Results
      indicated that (except for Traditional Religious Belief in women), the majority
      of these students were disbelievers in paranormal phenomena. As hypothesized,
      Latvian women reported significantly greater paranormal belief than men.

PMID- 25621675
TI  - Hemispheric activation during planning and execution phases in reaching post
      stroke: a consort study.
AB  - Enhanced activation in the non-lesion hemisphere in stroke patients was widely
      observed during movement of the affected upper limb, but its functional role
      related to motor planning and execution is still unknown.This study was to
      characterize the activation in the non-lesion hemisphere during movement planning
      and execution by localizing sources of high-density electroencephalography (EEG)
      signal and estimating the source strength (current density [A/m]).Ten individuals
      with chronic stroke and shoulder/elbow coordination deficits and 5 healthy
      controls participated in the study.EEG (64 channels) was recorded from scalp
      electrodes while the subjects performed a reach task involving shoulder flexion
      and elbow extension of the affected (patients) or dominant (controls) upper
      extremity. Sources of the EEG were obtained and analyzed at 17 time points across
      movement preparation and execution phases. A 3-layer boundary element model was
      overlaid and used to identify the brain activation sources. A distributed current
      density model, low-resolution electromagnetic tomography (LORETA) L1 norm method,
      was applied to the data pre-processed by independent component analysis.Subjects
      with stroke had stronger source strength in the sensorimotor cortices during the
      movement compared with the controls. Their contralesional/lesional activation
      ratio (CTLR) for the primary motor cortices was significantly higher than that of
      the controls during the movement-planning phase, but not during the execution
      phase. The CTLR was higher in planning than in the execution phase in the stroke
      group.Excessive contralesional motor cortical activation appears to be more
      related to movement preparation rather than execution in chronic stroke. 

PMID- 25621676
TI  - The gastric/pancreatic amylase ratio predicts postoperative pancreatic fistula
      with high sensitivity and specificity.
AB  - This article aims to identify risk factors for postoperative pancreatic fistula
      (POPF) and evaluate the gastric/pancreatic amylase ratio (GPAR) on postoperative
      day (POD) 3 as a POPF predictor in patients who undergo pancreaticoduodenectomy
      (PD).POPF significantly contributes to mortality and morbidity in patients who
      undergo PD. Previously identified predictors for POPF often have low predictive
      accuracy. Therefore, accurate POPF predictors are needed.In this prospective
      cohort study, we measured the clinical and biochemical factors of 61 patients who
      underwent PD and diagnosed POPF according to the definition of the International
      Study Group of Pancreatic Fistula. We analyzed the association between POPF and
      various factors, identified POPF risk factors, and evaluated the predictive power
      of the GPAR on POD3 and the levels of serum and ascites amylase.Of the 61
      patients, 21 developed POPF. The color of the pancreatic drain fluid, POD1 serum,
      POD1 median output of pancreatic drain fluid volume, and GPAR were significantly
      associated with POPF. The color of the pancreatic drain fluid and high GPAR were
      independent risk factors. Although serum and ascites amylase did not predict POPF
      accurately, the cutoff value was 1.24, and GPAR predicted POPF with high
      sensitivity and specificity.This is the first report demonstrating that high GPAR
      on POD3 is a risk factor for POPF and showing that GPAR is a more accurate
      predictor of POPF than the previously reported amylase markers. 

PMID- 25621677
TI  - Health care associated hematogenous pyogenic vertebral osteomyelitis: a severe
      and potentially preventable infectious disease.
AB  - Although hematogenous pyogenic spinal infections have been related to
      hemodialysis (HD), catheter-related sepsis, and sporadically, to other nosocomial
      infections or procedures, in most recent studies and reviews the impact of
      nosocomial infection as a risk factor for vertebral osteomyelitis (VO) is not
      well established. The aim of our study was to describe the risk factors,
      infectious source, etiology, clinical features, therapy, and outcome of health
      care associated VO (HCAVO), and compare them with community-acquired VO (CAVO)
      cases.A retrospective cohort study of consecutive patients with hematogenous VO
      was conducted in our third-level hospital between 1987 and 2011. HCAVO was
      defined as onset of symptoms after 1 month of hospitalization or within 6 months
      after hospital discharge, or ambulatory manipulations in the 6 months before the
      diagnosis.Over the 25-year study period, among 163 hematogenous pyogenic VO, 41
      (25%) were health care associated, a percentage that increased from 15% (9/61) in
      the 1987-1999 period to 31% (32/102) in the 2000-2011 period (P < 0.01). The
      presumed source of infection was an intravenous catheter in 14 (34%), cutaneous
      foci in 8 (20%), urinary tract in 7 (17%), gastrointestinal in 3 (7%), other foci
      in 3 (7%), and unknown in 6 (15%). Staphylococcus aureus was the most frequently
      isolated microorganism (14 cases, 34%), followed by coagulase-negative
      Staphylococci (CoNS) in 6 (15%), and Enterobacteriaceae in 6 (15%) cases.Compared
      with CAVO cases, patients with HCAVO were older (mean 66.0 SD 13.0 years vs 60.5
      SD 15.5 years), had more underlying conditions (73% vs 50%, P < 0.05),
      neoplasm/immunosuppression (39% vs 7%, P < 0.005), chronic renal failure (19% vs
      4%, P < 0.001), a known source of infection (85% vs 54% P < 0.05), Candida spp
      (7% vs 0%, P < 0.01) or CoNS infections (15% vs 2%, P < 0.05), higher mortality
      (15% vs 6%, P = 0.069), and a higher relapse rate in survivors (9% vs 1%, P <
      0.05).Presently, in our setting, one-third of hematogenous pyogenic VO infections
      are health care associated, and a third of these are potentially preventable
      catheter-related infections. Compared with CAVO, in health care associated
      hematogenous VO, mortality and relapse rates are higher; hence, further
      prevention measures should be assessed. 

PMID- 25621678
TI  - Malignant transformation in monostotic fibrous dysplasia: clinical features,
      imaging features, outcomes in 10 patients, and review.
AB  - Malignant transformation in fibrous dysplasia (FD) is uncommon. The purpose of
      this study was to investigate clinical and imaging features, and outcomes of
      malignant transformation in monostotic FD.Data for 10 pathologically confirmed
      malignant transformations in monostotic FD from January 2005 to December 2013
      were retrospectively reviewed. Patient data were recorded, and radiographs (n =
      10), computed tomography (CT) (n = 5), magnetic resonance (MR) (n = 4), and bone
      scintigrams (n = 10) were evaluated for lesion location, margin, cortical
      destruction, marrow involvement, periosteal reaction, and soft tissue mass by 2
      musculoskeletal radiologists with agreement by consensus. Clinical features,
      management, and prognosis were also analyzed for each of the 10 cases.There were
      8 male and 2 female patients (mean age 46.5 +/- 15.9 years). The affected sites
      were the femur (n = 4), humerus (n = 2), tibia (n = 3), and ilium (n = 1). Five
      cases had received previous surgery and 5 cases had no history of surgery. No
      patients had been given prior irradiation treatment. For the 5 cases with
      surgery, radiographs and CT showed purely osteolytic lesions with poor
      margination in the curettage area (n = 5), cortical destruction (n = 5), obvious
      soft tissue mass (n = 1), and mineralization (n = 2). For the 5 cases without
      surgery, radiographs and CT identified poorly marginated, osteolytic lesions
      within or near the area with "ground-glass" opacity (n = 4), cortical erosion (n
      = 4), and mineralization (n = 2). Magnetic resonance imaging (MRI) also
      identified lesions with heterogeneous signal intensity and pronounced
      enhancement. Bone scintigraphy revealed eccentric increased uptake of
      radionuclide in monostotic lesion (n = 10). Pathology reports revealed
      osteosarcoma (n = 7), fibrosarcoma (n = 2), and malignant fibrous histiocytoma
      (MFH) (n = 1). At the end of the study, 1 patient died from tumors, 1 patient was
      alive with lung metastasis, 1 patient experienced recurrence, and 7 patients were
      alive without recurrence.Patients with FD and a history of surgery should be
      followed up, for the osteolytic lesions in the operative areas strongly indicate
      the malignant transformation. The radiographic feature of FD-related malignancies
      is poorly marginated, mineralized, and osteolytic lesions with cortical
      destruction. Further investigations are needed to explore the pathogenesis of
      malignancies in FD and to establish optimal therapeutic strategies. 

PMID- 25621679
TI  - Extensive invasive extramammary Paget disease evaluated by F-18 FDG PET/CT: a
      case report.
AB  - Extramammary Paget disease (EMPD) is a rare cutaneous, intraepithelial
      adenocarcinoma. Because of its rarity, little is known about the value of
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) in evaluating this disease. Our case report aims to increase current
      knowledge of FDG PET/CT in EMPD as a noninvasive imaging tool for assessing the
      extension of the disease and detecting distant metastases.We reported a 64-year
      old Chinese man who presented with a slowly progressive, ill-margined
      erythematous lesion with a crusted, eroded, and scaly surface involving multiple
      sites of penis, scrotum, left pelvic wall, hip, groin, and thigh for >4 years,
      which became extensive in the past 1 year. He was referred for an FDG PET/CT
      examination to further evaluate the lesions. A following skin biopsy was
      performed to obtain a definitive histological diagnosis.FDG PET/CT imaging
      revealed mild FDG uptake at the extensive cutaneous lesion with subcutaneous
      invasion, involvement of lymph nodes, and multiple intense FDG-avid of skeletal
      metastases. According to the appearance of FDG PET/CT, a provisional diagnosis of
      advanced cutaneous malignancy was made. Histopathology findings indicated
      characteristic of EMPD. The patient was treated with radiation therapy and died
      from complications 2 months after the last dose of radiotherapy.Our case
      highlighted that a whole-body FDG PET/CT should be incorporated into the
      diagnostic algorithm of EMPD to give a comprehensive assessment of this disease. 

PMID- 25621680
TI  - Acute motor axonal neuropathy in a child with atypical presentation: a case
      report.
AB  - Acute motor axonal neuropathy (AMAN) is a variant of Guillain-Barre syndrome. It
      has been reported to have no sensory symptoms and is diagnosed by typical
      electrophysiological findings of low-amplitude or unobtainable compound muscle
      action potentials with normal sensory nerve action potentials. However, the
      authors experienced atypical case of general electrophysiological findings of
      AMAN with pain and paresthesia and presented it. This case implies that clinician
      should be on the alert to atypical sensory symptoms from the classical
      presentation of AMAN even if the patient is diagnosed with AMAN
      electrophysiologically and should consider proper treatment options based on
      clinical presentations. 

PMID- 25621681
TI  - Perivascular epithelioid cell tumor of gastrointestinal tract: case report and
      review of the literature.
AB  - Perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas) are
      exceedingly rare, with only a limited number of published reports worldwide.
      Given the scarcity of GI PEComas and their relatively short follow-up periods,
      our current knowledge of their biologic behavior, molecular genetic alterations,
      diagnostic criteria, and prognostic factors continues to be very limited.We
      present 2 cases of GI PEComas, one of which showed an aggressive histologic
      behavior that underwent multiple combined chemotherapies. We also review the
      available English-language medical literature on GI PEComas-not otherwise
      specified (PEComas-NOS) and discuss their clinicopathological and molecular
      genetic features.Pathologic analyses including histomorphologic,
      immunohistochemical, and ultrastructural studies were performed to evaluate the
      clinicopathological features of GI PEComas, their diagnosis, and differential
      diagnosis. Immunohistochemistry, semiquantitative reverse transcriptase
      polymerase chain reaction, and DNA sequencing assays were carried out to detect
      the potential molecular genetic alterations in our cases. Microscopically, the
      tumors showed distinctive histologic features of PEComas-NOS, including
      fascicular or nested architecture, epithelioid or spindled cell type, and clear
      to eosinophilic cytoplasm. The tumor cells were immunohistochemically positive
      for melanocytic markers. Molecular pathological assays confirmed a PSF-TFE3 gene
      fusion in one of our cases. Furthermore, in this case microphthalmia-associated
      transcription factor and its downstream genes were found to exhibit elevated
      transcript levels.Knowledge about the molecular genetic alterations in GI PEComas
      is still limited and warrants further study.

PMID- 25621682
TI  - Value of nerve biopsy in patients with latent malignant hemopathy and peripheral
      neuropathy: a case series.
AB  - Hematological malignancies include several diseases that may affect the
      peripheral nervous system (PNS) through various mechanisms. A common and
      challenging situation is represented by the occurrence of an active peripheral
      neuropathy in a patient with a supposed inactive hematological disorder.We report
      clinical, electrophysiological, biological, and pathological data of 8 patients
      with latent malignant hemopathies (most were considered in remission): B-cell
      chronic lymphocytic leukemia in 3 patients, B-cell lymphoma in 1 patient, low
      grade non-Hodgkin's lymphoma in 1 patient, Waldenstrom's macroglobulinemia in 1
      patient, smoldering multiple myeloma in 1 patient, and monoclonal gammopathy of
      undetermined significance in 1 patient.In all these cases, the nerve biopsy (NB)
      helped to diagnose the hematological relapse or detect a pathological mechanism
      linked to the hematological disorder: epineurial lymphocytic infiltration in 5
      patients (including one with antimyelin-associated glycoprotein antibodies),
      cryoglobulin deposits in 1 patient, chronic inflammatory demyelinating
      polyneuropathy in 1 patient, and necrotizing vasculitis in 1 patient. In each
      case, pathological findings were crucial to select the adequate treatment,
      leading to an improvement in the neurological and biological manifestations.These
      observations illustrate the value of NB and the need for active collaboration
      between neurologists and hematologists in such cases. 

PMID- 25621683
TI  - Lymph node count after preoperative radiotherapy is an independently prognostic
      factor for pathologically lymph node-negative patients with rectal cancer.
AB  - Recent studies indicated that preoperative radiotherapy significantly reduces the
      lymph nodes (LNs) harvest from patients with rectal cancer. This may weaken the
      prognostic value of current standard of LNs retrieval (>=12 LNs). This study
      investigates the prognostic impact of the LN counts on pathologically LN-negative
      (ypN0) after preoperative radiotherapy for patients with rectal
      cancer.Surveillance, Epidemiology and End Results (SEER) registered nonmetastatic
      rectal cancer patients diagnosed between 1998 and 2005 were included in this
      study. Optimal cutoff value for number of LNs retrieved was determined by X-tile
      program. Log-rank tests were adopted to compare the rectal cause specific
      survival (RCSS) for ypN0 patients using separated cutoff value of LN counting
      from 2 to 20. Correlation between LN count and tumor regression was investigated
      in an additional 221 patients from Fudan University Shanghai Cancer Center
      (FUSCC).The results showed that there were fewer number of LNs examined in
      patients with preoperative radiotherapy than those without (8.9 vs 10.9, P <
      0.001). X-tile program identified the difference in survival was most significant
      (maximum of chi log-rank values) for the number 4. And 5-year RCSS increased
      accordingly with the cutoff values ranging from 4 to 15, which were confirmed as
      optimal cutoff and validated as independent prognostic factors in multivariate
      regression analysis (chi = 50.65, P < 0.001). Patients in FUSCC set were found to
      have fewer LNs retrieval in group of good tumor regression than in that of poor
      one (P = 0.01).These results confirmed the reduced number of LN retrieval in
      patients with rectal cancer treated with preop-RT. LN count is still an
      independently prognostic factor for ypN0 rectal cancer. 

PMID- 25621685
TI  - Arrangements of hepatobiliary cystadenoma complicated with congenital choledochal
      cyst: a case report and literature review.
AB  - Hepatobiliary cystadenoma complication with congenital choledochal cyst is
      extremely rare and has never been reported in literatures so far.The aim of the
      study was to investigate the disease arrangements by analyzing the case and
      performing a systematic review of the literature.This case report documents the
      details and clear patterns of the patient. A 65-year-old woman with fever (39.2
      degrees C), nausea, vomiting, and chronic hepatitis B imaging demonstrated a left
      hepatic multilocular cystic mass and cystic dilated common bile duct.A regular
      left hemihepatectomy was performed with resection of the entire tumor and
      choledochal cyst.The surgical margins were negative and a final diagnosis of
      hepatobiliary cystadenoma complicated with congenital choledochal cyst was
      established. The patient had an uneventful postoperative recovery and liver
      function returned to normal levels.Main lessons learned from this case are: the
      awareness should be raised about the disease to avoid misdiagnosis; preoperative
      ultrasonography, computed tomography, magnetic resonance imaging, and magnetic
      resonance cholangiopancreatography play an important role in detecting the
      lesion; the scope and timing of the surgery should be determined, which provide
      the chance of cure to complete resection of the tumor. 

PMID- 25621684
TI  - Hepatic resection as a safe and effective treatment for hepatocellular carcinoma
      involving a single large tumor, multiple tumors, or macrovascular invasion.
AB  - This systematic review examined whether the available evidence justifies using
      hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC),
      which contravenes treatment guidelines but is current practice at many medical
      centers.Official guidelines and retrospective studies recommend different roles
      for HR for patients with large/multinodular HCC or with HCC involving
      macrovascular invasion (MVI).Several databases were systematically searched for
      studies examining the safety and efficacy of HR for treating HCC involving a
      single large tumor (>5 cm) or multiple tumors, or for treating HCC involving
      MVI.We identified 50 studies involving 14, 808 patients that investigated the use
      of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that
      investigated HR to treat HCC with MVI. Median in-hospital mortality for patients
      with either type of HCC was significantly lower in Asian studies (2.7%) than in
      non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was
      significantly higher for all Asian patients with large/multinodular HCC than for
      all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs
      32%, P < 0.001). Similar results were obtained for median disease-free survival
      at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However,
      median OS was similar for Asian and non-Asian patients with HCC involving MVI at
      1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an
      upward trend in 5-year OS in patients with either type of HCC.HR is reasonably
      safe and effective at treating large/multinodular HCC and HCC with MVI. The
      available evidence argues for expanding the indications for HR in official
      treatment guidelines.

PMID- 25621686
TI  - Spinal cord and spinal nerve root involvement (myeloradiculopathy) in tuberculous
      meningitis.
AB  - Most of the information about spinal cord and nerve root involvement in
      tuberculous meningitis is available in the form of isolated case reports or case
      series. In this article, we evaluated the incidence, predictors, and prognostic
      impact of spinal cord and spinal nerve root involvement in tuberculous
      meningitis.In this prospective study, 71 consecutive patients of newly diagnosed
      tuberculous meningitis were enrolled. In addition to clinical evaluation,
      patients were subjected to magnetic resonance imaging (MRI) of brain and spine.
      Patients were followed up for at least 6 months.Out of 71 patients, 33 (46.4%)
      had symptoms/signs of spinal cord and spinal nerve root involvement, 22 (30.9%)
      of whom had symptoms/signs at enrolment. Eleven (15.4%) patients had paradoxical
      involvement. Paraparesis was present in 22 (31%) patients, which was of upper
      motor neuron type in 6 (8.4%) patients, lower motor neuron type in 10 (14%)
      patients, and mixed type in 6 (8.4%) patients. Quadriparesis was present in 3
      (4.2%) patients. The most common finding on spinal MRI was meningeal enhancement,
      seen in 40 (56.3%) patients; in 22 (30.9%), enhancement was present in the
      lumbosacral region. Other MRI abnormalities included myelitis in 16 (22.5%),
      tuberculoma in 4 (5.6%), cerebrospinal fluid (CSF) loculations in 4 (5.6%), cord
      atrophy in 3 (4.2%), and syrinx in 2 (2.8%) patients. The significant predictor
      associated with myeloradiculopathy was raised CSF protein (>250 mg/dL).
      Myeloradiculopathy was significantly associated with poor outcome.In conclusion,
      spinal cord and spinal nerve root involvement in tuberculous meningitis is
      common. Markedly raised CSF protein is an important predictor. Patients with
      myeloradiculopathy have poor outcome. 

PMID- 25621687
TI  - Simplified classification of capillary pattern in Barrett esophagus using
      magnifying endoscopy with narrow band imaging: implications for malignant
      potential and interobserver agreement.
AB  - The classification of Barrett esophagus (BE) using magnifying endoscopy with
      narrow band imaging (ME-NBI) is not widely used in clinical settings because of
      its complexity. To establish a new simplified available classification using ME
      NBI.We conducted a cross-sectional study in a single-referral center. One hundred
      eight consecutive patients with BE using ME-NBI and crystal violet (CV)
      chromoendoscopy, and histological findings were enrolled. BE areas observed by ME
      NBI were classified as type I or II on the basis of capillary pattern (CP), and
      as closed or open type on the basis of a mucosal pit pattern using CV
      chromoendoscopy; then, biopsy samples were obtained. We evaluated the relation
      between CP and pit pattern, expression of the factors with malignant potential,
      percentage of microvascular density, and interobserver agreement.One hundred
      thirty lesions from 91 patients were analyzed. Type II CP had more open type pit
      pattern areas and significantly greater microvascular density than type I. The
      presence of dysplasia, specialized intestinal metaplasia, expressions of COX-2,
      CDX2, and CD34, and PCNA index were significantly higher in type II, whereas the
      multivariate analysis showed that type II was the best predictor for the presence
      of dysplasia (OR 11.14), CD34 expression (OR 3.60), and PCNA (OR 3.29).
      Interobserver agreement for this classification was substantial (kappa = 0.66).A
      simplified CP classification based on observation with ME-NBI is presented. Our
      results indicate that the classification may be useful for surveillance of BE
      with high malignant potential. 

PMID- 25621688
TI  - The effect of testosterone replacement therapy on prostate-specific antigen (PSA)
      levels in men being treated for hypogonadism: a systematic review and meta
      analysis.
AB  - Testosterone replacement therapy is used for the treatment of age-related male
      hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for
      prostate cancer. The systematic review and meta-analysis aimed to determine the
      effect of testosterone replacement therapy on PSA levels.Medline, Cochrane
      Library, EMBASE, and Google Scholar databases were searched until February 28,
      2014, and inclusion criteria were as follows: randomized controlled trial;
      intervention group received testosterone/androgen replacement therapy; control
      group did not receive treatment; and no history of prostate cancer. The primary
      outcome was change of PSA level between before and after treatment. Secondary
      outcomes were elevated PSA level after treatment, and the number of patients who
      developed prostate cancer.After initially identifying 511 articles, 15 studies
      with a total of 739 patients that received testosterone replacement and 385
      controls were included. The duration of treatment ranged from 3 to 12 months.
      Patients treated with testosterone tended to have higher PSA levels, and thus a
      greater change than those that received control treatments (difference in means
      of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001).
      The difference in means of PSA levels were significant higher for patients that
      received testosterone intramuscularly (IM) than controls (difference in means of
      PSA levels = 0.271, 95% CI 0.117-0.425, P = 0.001). Elevated PSA levels after
      treatment were similar between patients that received treatment and controls
      (odds ratio [OR] = 1.02, 95% CI 0.48-2.20, P = 0.953). Only 3 studies provided
      data with respect to the development of prostate cancer, and rates were similar
      between those that received treatment and controls.Testosterone replacement
      therapy does not increase PSA levels in men being treated for hypogonadism,
      except when it is given IM and even the increase with IM administration is
      minimal. 

PMID- 25621689
TI  - High social anxiety and poor quality of life in patients with pulmonary
      tuberculosis.
AB  - Pulmonary tuberculosis (PT) has been previously related with various psychosocial
      adverse consequences including stigmatization and social isolation.Social anxiety
      is a psychiatric condition that may be associated with social isolation and fear
      of social exclusion.To date no study has investigated social anxiety and its
      impact on quality of life (QoL) among patients with PT. Therefore, we aimed to
      determine the severity of social anxiety in a group of patients with PT.Among
      patients who were recently discharged from hospital with the diagnosis of PT 94
      patients and 99 healthy control subjects who had similar demographical features
      have been included in the study. A psychiatrist interviewed all participants and
      a semistructured interview form, which was prepared by the authors, Liebowitz
      Social Anxiety Scale (LSAS), and Short Form-36 were administered to them.Patients
      with PT showed higher levels of performance avoidance and social avoidance than
      healthy control subjects. They reported lower QoL scores across all dimensions.
      Among patients women showed higher levels of LSAS subscale scores and total
      score. Fear of social exclusion was predicted by perceived illness severity and
      emotional role difficulty. On the other hand, perceived illness severity was
      predicted by fear of exclusion and sedimentation level.PT patients seem to
      experience higher levels of social anxiety and associated fear of social
      exclusion that add to their worse QoL during the earlier months of their disease.
      Among them fear of social exclusion is related with perceived illness severity. 

PMID- 25621690
TI  - Does metaphyseal cement augmentation in fracture management influence the
      adjacent subchondral bone and joint cartilage?: an in vivo study in sheep stifle
      joints.
AB  - Augmentation of implants with polymethylmethacrylate (PMMA) bone cement in
      osteoporotic fractures is a promising approach to increase implant purchase. Side
      effects of PMMA for the metaphyseal bone, particularly for the adjacent
      subchondral bone plate and joint cartilage, have not yet been studied. The
      following experimental study investigates whether subchondral PMMA injection
      compromises the homeostasis of the subchondral bone and/or the joint
      cartilage.Ten mature sheep were used to simulate subchondral PMMA injection.
      Follow-ups of 2 (4 animals) and 4 (6 animals) months were chosen to investigate
      possible cartilage damage and subchondral plate alterations in the knee.
      Evaluation was completed by means of high-resolution peripheral quantitative
      computed tomography (HRpQCT) imaging, histopathological osteoarthritis scoring,
      and determination of glycosaminoglycan content in the joint cartilage. Results
      were compared with the untreated contralateral knee and statistically analyzed
      using nonparametric tests.Evaluation of the histological osteoarthritis score
      revealed no obvious cartilage damage for the treated knee; median histological
      score after 2 months 0 (range 4), after 4 months 1 (range 5). There was no
      significant difference when compared with the untreated control site after 2 and
      4 months (P = 0.23 and 0.76, respectively). HRpQCT imaging showed no damage to
      the metaphyseal trabeculae. Glycosaminoglycan measurements of the treated joint
      cartilage after 4 months revealed no significant difference compared with the
      untreated cartilage (P = 0.24).The findings of this study support initial
      clinical observation that PMMA implant augmentation of metaphyseal fractures
      appears to be a safe procedure for fixation without harming the subchondral bone
      plate and adjacent joint cartilage. 

PMID- 25621691
TI  - Repeatability of blood gas parameters, PCO2 gap, and PCO2 gap to arterial-to
      venous oxygen content difference in critically ill adult patients.
AB  - The objective of this study was to examine the repeatability of blood gas (BG)
      parameters and their derived variables such as the central venous-to-arterial
      carbon dioxide tension difference (?PCO2) and the ratio of ?PCO2 over the central
      arteriovenous oxygen content difference (?PCO2/C(a-cv)O2) and to determine the
      smallest detectable changes in individual patients.A total of 192 patients with
      arterial and central venous catheters were included prospectively. Two subsequent
      arterial and central venous blood samples were collected immediately one after
      the other and analyzed using the same point-of-care BG analyzer. The samples were
      analyzed for arterial and venous BG parameters, ?PCO2, and ?PCO2/C(a-cv)O2 ratio.
      Repeatability was expressed as the smallest detectable difference (SDD) and the
      least significant change (LSC). A change in value of these parameters exceeding
      the SDD or the LSC should be regarded as real.The SDDs for arterial carbon
      dioxide tension, arterial oxygen saturation, central venous oxygen saturation
      (ScvO2), and ?PCO2 were small: +/-2.06 mm Hg, +/-1.23%, 2.92%, and +/-1.98 mm Hg,
      respectively, whereas the SDDs for arterial oxygen tension (PaO2) and ?PCO2/C(a
      cv)O2 were high: +/-9.09 mm Hg and +/-0.57 mm Hg/mL, respectively. The LSCs (%)
      for these variables were 5.06, 1.27, 4.44, 32.4, 9.51, and 38.5, respectively.The
      repeatability of all these variables was good except for PaO2 and ?PCO2/C(a-cv)O2
      ratio for which we observed an important inherent variability. Expressed as SDD,
      a ScvO2 change value of at least +/-3% should be considered as true. The
      clinician must be aware that an apparent change in these variables in an
      individual patient might represent only an inherent variation. 

PMID- 25621692
TI  - Professional continuous glucose monitoring for the identification of type 1
      diabetes mellitus among subjects with insulin therapy.
AB  - The identification of type 1 diabetes in diabetic subjects receiving insulin
      therapy is sometimes difficult. The purpose of this study is to evaluate whether
      results of professional continuous glucose monitoring can improve the
      identification of type 1 diabetes.From 2007 to 2012, 119 adults receiving at
      least twice-daily insulin therapy and professional continuous glucose monitoring
      were recruited. Type 1 diabetes was diagnosed by endocrinologists according to
      American Diabetes Association standards, including a very low C-peptide level
      (<0.35  pg/mL) or the presence of diabetic ketoacidosis. Continuous glucose
      monitoring was applied for 3 days.Among 119 subjects, 86 were diagnosed with type
      1 diabetes. Subjects with type 1 diabetes were younger (33.8 vs 52.3 years old, P
      < 0.001), had lower body mass index (BMI, 21.95 vs 24.42, P = 0.003), lower serum
      creatinine (61.77  vs 84.65 MUmol/L, P = 0.001), and higher estimated glomerular
      filtration rate (108.71 vs 76.48 mg/mL/min/1.73m2, P < 0.001) than subjects with
      type 2 diabetes. Predictive scores for identification of type 1 diabetes were
      constructed, including age, BMI, average mean amplitude of glucose excursion in
      days 2 and 3, and the area under the curve of nocturnal hyperglycemic and
      hypoglycemic states. The area under the receiver operating characteristic curve
      was 0.90. With the cutoff of 0.58, the sensitivity was 86.7% and the specificity
      was 80.8%. The good performance was validated by the leave-one-out method
      (sensitivity 83.3%, specificity 73.1%).Professional continuous glucose monitoring
      is a useful tool that improves identification of type 1 diabetes among diabetic
      patients receiving insulin therapy.

PMID- 25621693
TI  - Complex regional pain syndrome and acute carpal tunnel syndrome following radial
      artery cannulation: a neurological perspective and review of the literature.
AB  - Complex regional pain syndrome (CRPS) associated with acute carpal tunnel
      syndrome (aCTS) developed in a 38-year-old right-handed man following radial
      artery cannulation (RAC) during the course of lumbar spine surgery. Inciting
      events and risk factors that might have led to these complications included:
      multiple arterial punctures and subsequent hematoma formation, radial artery
      spasm compounded by aggressive hemostasis, anatomical changes in the wrists
      related to repetitive manual activities in the workplace, and possible protracted
      hyperextension of the wrists during perioperative and operative procedure.
      Although CRPS is considered a rare complication of RAC, the condition is
      disabling and debilitating, especially when associated with aCTS. 

PMID- 25621694
TI  - Effects of angiotensin converting enzyme inhibition or angiotensin receptor
      blockade in dialysis patients: a nationwide data survey and propensity analysis.
AB  - Long-term benefit of using a renin-angiotensin-aldosterone system blocker such as
      an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor
      blocker (ARB) for patients already receiving dialysis remains undetermined. The
      aim of this study is to assess the efficacy and safety of ACEI or ARB use in
      dialysis patients. We performed a population-based cohort study with time-to
      event analyses to estimate the relation between the use of ACEI/ARB and their
      outcomes. We used a nationwide database (Registry for Catastrophic Illnesses) for
      Taiwan, which has data from 1995 to 2008 nearly of all patients who received
      dialysis therapy. The records of all dialysis patients aged >=18 with no evidence
      of cardiovascular (CV) events in 1997 and 1998 (133,564 patients) were examined.
      Users (n = 50,961) and nonusers (n = 59,913) of an ACEI/ARB were derived. We then
      used propensity score matching and Cox proportional hazards regression models to
      estimate adjusted hazard ratios (HRs) for all-cause mortality and CV events in
      users and nonusers of an ACRI/ARB. The 15,182 patients, who used an ACEI/ARB, and
      the 15,182 nonusers had comparable baseline characteristics during the 14 years
      of follow-up. The mortality was significantly greater in patients who did not use
      an ACEI/ARB (HR = 0.90, 95% confidence interval = 0.86-0.93). Subgroup analysis
      of 3 tertiles of patients who used different total amounts of ACEI/ARB during the
      study period indicated that CV events were more common in patients who used an
      ACEI/ARB for a short duration (tertile 1: HR = 1.63), but less common in those
      who used an ACEI/ARB for long durations (tertile 2: HR = 1.05; tertile 3: HR =
      0.94; trend for declining HR from tertile 1 to 3: P < 0.001). The mortality
      benefit provided by use of an ACEI/ARB was consistent across most patient
      subgroups, as was the benefit of ARB monotherapy rather than ACEI monotherapy.
      Independent of traditional risk factors, overall mortality was significantly
      lower in dialysis patients who used an ACEI/ARB. In addition, subjects who used
      an ACEI/ARB for longer durations were significantly less likely to experience CV
      events. 

PMID- 25621695
TI  - Riedel's lobe of the liver: a case report.
AB  - Riedel lobe of the liver is a simple anatomical variation, a downward tongue-like
      projection of the anterior edge of the right lobe of the liver to the right of
      the gallbladder with its typical case to be rare.We report the case of a 71-year
      old woman with typical feature of a nonpalpable Riedel's lobe of the liver, as an
      incidental finding who was referred for reported hypergammaglobulinemia (22.7%
      [9%-19%]). Both features were attributed to a chronic inflammation because of an
      abscess in the right iliopsoas caused by infection due to bilateral hip
      replacement which underwent revision surgery. This was confirmed by her medical
      history, the imaging findings combined with elevated C-reactive protein, and by
      cross-reaction weak positive autoantibodies.Generally, knowledge or suspicion of
      Riedel's lobe of the liver is important, as it does not always remain clinically
      latent, as in our case, and it can be complicated by its torsion or hepatic
      tumors. 

PMID- 25621696
TI  - MELD scores and Child-Pugh classifications predict the outcomes of ERCP in
      cirrhotic patients with choledocholithiasis: a retrospective cohort study.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in cirrhotic
      patients with choledocholithiasis. We evaluated the safety and efficacy of ERCP
      in cirrhotic patients with choledocholithiasis and accessed the model for end
      stage liver disease (MELD) scores and Child-Pugh classifications for prediction
      of morbidity and mortality.From January 2000 to June 2014, 77 ERCP operations
      were performed in cirrhotic patients with choledocholithiasis. The data on
      operative complications were analyzed. MELD scores and Child-Pugh classifications
      were calculated and associated with operative outcomes and survival. Telephone
      follow-up was performed to determine survival situations.No death, perforation,
      or hemorrhage caused by gastroesophageal varices occurred as a result of the
      procedure. The rate of intraoperative hemorrhage was 13.0%, and the rate of
      postoperative morbidity was 27.3% including hemorrhage (18.2%), post-ERCP
      pancreatitis (6.1%), aggravated infection of the biliary tract (1.3%), hepatic
      encephalopathy (1.3%), and respiratory failure (1.3%). Four (5.2%) patients had
      both intraoperative and postoperative hemorrhage. Receiver operating
      characteristic analysis identified MELD scores higher than 11.5 as the best
      cutoff value for predicting complication incidence (95% confidence interval =
      0.63-0.87). Twenty-one (44.7%) patients with a MELD score above 11.5 developed a
      complication, and 3 (10%) patients who had a lower MELD score developed a
      complication (P = 0.001). Both MELD score and Child-Pugh classification had
      prognostic value in patients without jaundice, although sex may result in
      different prognostic values based on the 2 scores. The rate of complications was
      not significantly different among patients with different Child-Pugh
      classifications. No significant difference was observed in patients with
      different MELD scores or Child-Pugh classifications in terms of median survival
      times.ERCP is an effective and safe procedure in cirrhotic patients with
      choledocholithiasis. MELD scores can predict the risk of operative complications,
      but Child-Pugh classification system scores do not predict the risk of
      complications. 

PMID- 25621697
TI  - Predictive value of 18F-FDG PET and CT morphologic features for recurrence in
      pathological stage IA non-small cell lung cancer.
AB  - Patients with pathological stage IA non-small cell lung cancer (NSCLC) may
      relapse despite complete surgical resection without lymphovascular invasion. A
      method of selecting a high-risk group for adjuvant therapy is necessary. The aim
      of this study was to assess the predictive value of F-fluorodeoxyglucose (FDG)
      uptake and the morphologic features of computed tomography (CT) for recurrence in
      pathological stage IA NSCLC.One hundred forty-five patients with pathological
      stage IA NSCLC who underwent pretreatment with FDG positron emission tomography
      and CT evaluations were retrospectively enrolled. The associations among tumor
      recurrence and patient characteristics, maximal standard uptake value (SUVmax) of
      primary tumors, and CT imaging features were investigated using univariate and
      multivariate analyses. A receiver operating characteristic (ROC) curve analysis
      was performed to quantify the predictive value of these factors.Tumor recurrence
      developed in 21 (14.5%) of the 145 patients, and the 5-year recurrence-free
      survival rate was 77%. The univariate analysis demonstrated that SUVmax, the
      grade of histological differentiation, tumor size, and the presence of
      bronchovascular bundle thickening were significant predictive factors (P < 0.05).
      A higher SUVmax (>=2.5) (P = 0.021), a lower ground-glass opacity ratio (<=17%)
      (P = 0.014), and the presence of bronchovascular bundle thickening (P = 0.003)
      were independent predictive factors of tumor recurrence in the multivariate
      analysis. The use of this predictive model yielded a greater area under the ROC
      curve (0.877), which suggests good discrimination.The combined evaluation of FDG
      uptake and CT morphologic features may be helpful in the prediction of recurrence
      in patients with pathological stage IA NSCLC and in the stratification of a high
      risk group for postoperative adjuvant therapy or prospective clinical trials. 

PMID- 25621698
TI  - Case report of an endovascular repair of a residual type A dissection using a not
      CE not FDA-approved Najuta thoracic stent graft system.
AB  - This report describes an endovascular repair of a residual type A dissection
      using a medical device that is not marked by european conformity (CE) or Food and
      Drug Administration (FDA).The patient underwent ascending aortic surgery for
      acute type A dissection. The 2-year angio-computed tomography demonstrated
      patency of the residual false lumen with evolution into a 6 cm aneurysm, the
      extension of the dissection from the aortic arch to the aortic bifurcation with
      thrombosis of the right common iliac artery. There was no CE- or FDA-marked
      medical device indicated for this case or any other acceptable therapeutic
      alternative.We used the Najuta thoracic stent graft and successfully handled the
      pathology in a multiple-phase treatment.Technology is evolving with specific
      grafts for the ascending and fenestrated grafts for the aortic arch. In this
      single case the Najuta endograft, in spite of the periprocedural problems, was a
      valid therapeutic option. 

PMID- 25621699
TI  - CT findings and clinical features of pancreatic hemolymphangioma: a case report
      and review of the literature.
AB  - Pancreatic hemolymphangioma is a very rare benign tumor. There were only 10
      reports of this disease until June 2014.The aim of the present study was to
      describe a hemolymphangioma in the neck and body of the pancreas in a 57-year-old
      woman.The method used in the present study consists of description of the
      clinical history, image lab features, and pathological result.The patient
      complained of a 10-day history of epigastric discomfort. Abdominal computed
      tomography (CT) showed a cystic-solid tumor with an irregular shape, in the neck
      and body of the pancreas. The tumoral cystic wall and its internal division could
      be seen intensified on contrast-enhanced CT images compared with those on
      precontrast images. The pathological examination confirmed the diagnosis.The
      clinical feature of pancreatic hemolymphangioma includes a lack of specificity.
      The CT appearance combined with age and sex may be useful in making an early
      diagnosis. 

PMID- 25621700
TI  - Discovery of a new family of Dieckmann cyclases essential to tetramic acid and
      pyridone-based natural products biosynthesis.
AB  - Bioinformatic analyses indicate that TrdC, SlgL, LipX2, KirHI, and FacHI belong
      to a group of highly homologous proteins involved in biosynthesis of actinomycete
      derived tirandamycin B, streptolydigin, alpha-lipomycin, kirromycin, and
      factumycin, respectively. However, assignment of their biosynthetic roles has
      remained elusive. Gene inactivation and complementation, in vitro biochemical
      assays with synthetic analogues, point mutations, and phylogenetic tree analyses
      reveal that these proteins represent a new family of Dieckmann cyclases that
      drive tetramic acid and pyridone scaffold biosynthesis. 

PMID- 25621701
TI  - A feasible approach to evaluate the relative reactivity of NHS-ester activated
      group with primary amine-derivatized DNA analogue and non-derivatized impurity.
AB  - Synthetic DNA analogues with improved stability are widely used in life science.
      The 3'and/or 5' equivalent terminuses are often derivatized by attaching an
      active group for further modification, but a certain amount of non-derivatized
      impurity often remains. It is important to know to what extent the impurity would
      influence further modification. The reaction of an NHS ester with primary amine
      is one of the most widely used options to modify DNA analogues. In this short
      communication, a 3'-(NH2-biotin)-derivatized morpholino DNA analogue (MORF) was
      utilized as the model derivatized DNA analogue. Inclusion of a biotin concomitant
      with the primary amine at the 3'-terminus allows for the use of streptavidin to
      discriminate between the products from the derivatized MORF and non-derivatized
      MORF impurity. To detect the MORF reaction with NHS ester, S-acetyl NHS-MAG3 was
      conjugated to the DNA analogue for labeling with (99m)Tc, a widely used nuclide
      in the clinic. It was found that the non-derivatized MORF also reacted with the S
      acetyl NHS-MAG3. Radiolabeling of the product yielded an equally high labeling
      efficiency. Nevertheless, streptavidin binding indicated that under the
      conditions of this investigation, the non-derivatized MORF was five times less
      reactive than the amine-derivatized MORF. 

PMID- 25621702
TI  - Synthesis of novel 4'alpha-trifluoromethyl-2'beta-C-methyl-carbodine analogs as
      anti-hepatitis C virus agents.
AB  - Novel 4 'alpha-trifluoromethyl-2 'beta-methyl carbocyclic nucleoside analogs have
      been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA
      replication in cell cultures. Construction of cyclopentene intermediate 10a was
      achieved via sequential Johnson-Claisen orthoester rearrangement and ring-closing
      metathesis starting from the alpha-trifluoromethyl-alpha,beta-unsaturated ester
      5. Stereoselective dihydroxylation and desilylation yielded the target carbodine
      analogs. The synthesized nucleoside analogs mentioned above (18 and 19) were
      assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon
      Huh7 cell line (LucNeo#2). However, the synthesized nucleosides showed neither
      significant antiviral activity nor toxicity up to 50 MUM. 

PMID- 25621703
TI  - Highly regioselective C-5 iodination of pyrimidine nucleotides and subsequent
      chemoselective Sonogashira coupling with propargylamine.
AB  - An efficient C-5 iodination of pyrimidine-5'-triphosphates and subsequent
      palladium-catalyzed Sonogashira coupling reaction with propargylamine is
      described. The iodination reaction is highly regioselective and the coupling
      reaction is highly chemoselective that furnishes exclusive 5-(3-aminopropargyl)
      pyrimidine-5'-triphosphate in good yield with high purity (>99%). 

PMID- 25621704
TI  - In NMR tube transcription for rapid screening of RNA conformation.
AB  - A simple method for rapid structure screening for RNA by NMR is proposed. Target
      RNA is transcribed in a NMR tube and its spectra are measured without
      purification. The proposed method, in NMR tube transcription or INTT, was applied
      for three RNAs for which NMR spectra have been measured by using the
      conventionally purified samples. By the real-time measuring, increase of imino
      proton signals and decrease of NTP signals can be observed. It was confirmed that
      INTT spectra are in general similar to those obtained by the conventional method.
      INTT can be used for the first-step screening of RNA folding. 

PMID- 25621705
TI  - Synthesis of 2'-O-photocaged ribonucleoside phosphoramidites.
AB  - The chemical synthesis and incorporation of the phosphoramidite derivatives of 2
      '-O-photocaged ribonucleosides (A, C, G and U) with o-nitrobenzyl, alpha-methyl-o
      nitrobenzyl or 4,5-dimethoxy-2-nitrobenzyl group into oligoribonucleotides are
      described. The efficiency of UV irradiated uncaging of these 2'-O-photocaged
      oligoribonucleotides was found in the order of alpha-methyl-o-nitrobenzyl < 4,5
      dimethoxy-2-nitrobenzyl < 2'-O-o-nitrobenzyl. 

PMID- 25621706
TI  - Synthesis of novel 2',3'-difluorinated 5'-deoxythreosyl phosphonic acid
      nucleosides as antiviral agents.
AB  - A novel route for the synthesis of 2',3'-difluorinated 5'-deoxythreosyl
      phosphonic acid nucleosides from glyceraldehyde using the Horner-Emmons reaction
      in the presence of triethyl alpha-fluorophosphonoacetate is described. The second
      fluorination at the 2'-position was an electrophilic reaction performed using N
      fluorodibenzenesulfonimide. Glycosylation reactions between the nucleosidic bases
      and glycosyl donor 9 generated nucleosides that were further phosphonated and
      hydrolyzed to produce the desired nucleoside analogues. The synthesized
      nucleoside analogues 13, 16, 20, and 23 were tested for anti- human
      immunodeficiency virus (HIV) activity as well as cytotoxicity. Adenine derivative
      16 showed significant anti-HIV activity up to 100 MUM. 

PMID- 25621707
TI  - Controlling biofilms on cultural materials: the role of 3-(dodecane-1-thiyl)-4
      (hydroxymethyl)-2,2,5,5-tetramethyl-1-pyrrolinoxyl.
AB  - 3-(Dodecanethiyl)-4-(hydroxymethyl)-2,2,5,5-tetramethyl-1-pyrrolinoxyl (5)
      effectively disperses biofilms of relevance to cultural materials while
      preventing their formation.

PMID- 25621708
TI  - Non-canonical activation of inflammatory caspases by cytosolic LPS in innate
      immunity.
AB  - Lipopolysaccharide (LPS) is the major component of Gram-negative bacteria cell
      wall. In innate immunity, extracellular LPS is recognized by Toll-like receptor 4
      to stimulate cytokine transcription. Recent studies suggest a 'non-canonical
      inflammasome' that senses cytoplasmic LPS and activates caspase-11 in mouse
      macrophages. Unexpectedly, biochemical studies reveal that caspase-11 and its
      human orthologs caspase-4/caspase-5 are LPS receptors themselves. Direct LPS
      binding induces caspase-4/caspase-5/caspase-11 oligomerization and activation,
      triggering cell pyroptosis and anti-bacterial defenses. Caspase-4/caspase
      5/caspase-11 recognition of intracellular LPS requires bacterial escape from the
      vacuole; this process is promoted by interferon-inducible GTPases-mediated lysis
      of the bacteria-containing vacuole. Non-canonical activation of these
      inflammatory caspases by LPS not only represents a new paradigm in innate
      immunity but also critically determines LPS-induced septic shock in mice. 

PMID- 25621709
TI  - The NAIP/NLRC4 inflammasomes.
AB  - Inflammasomes comprise a family of cytosolic multi-protein complexes that sense
      infection, or other threats, and initiate inflammation via the recruitment and
      activation of the Caspase-1 protease. Although the precise molecular mechanism by
      which most inflammasomes are activated remains a subject of considerable debate,
      the NAIP/NLRC4 subfamily of inflammasomes is increasingly well understood. A
      crystal structure of NLRC4 was recently reported, and a domain in NAIPs that
      recognizes bacterial ligands was identified. In addition, gain-of-function
      mutations in NLRC4 have been shown to cause an auto-inflammatory syndrome in
      humans. Lastly, the NAIP/NLRC4 inflammasome has been shown to provide a novel
      form of cell intrinsic defense against Salmonella infection, involving expulsion
      of infected cells from the intestinal epithelium. 

PMID- 25621710
TI  - Risk factors for cranial nerve deficits during carotid endarterectomy: a
      retrospective study.
AB  - BACKGROUND: Cranial nerve deficits during CEA are a known complication. The
      purpose of this study is to evaluate if significant changes in somatosensory
      evoked potentials and electroencephalography increase cranial nerve deficits
      during CEA. PROCEDURES: This is an observational retrospective case-control study
      analyzed with data collected from patients who underwent CEA at the University of
      Pittsburgh Medical Center. Five hundred and eighty-seven patients were included
      in the final analysis. Due to the small number of cranial nerve deficits and the
      comparatively large number of potential covariates, we used a regression analysis
      with Bayesian shrinkage. FINDINGS: Analysis was performed on 587 patients, of
      which a total of 11 (1.8%) cases of cranial nerve deficits were recorded. The
      marginal mandibular branch of the facial nerve was injured in nine (81%) patients
      and hypoglossal nerve was injured in two (19%) patients. Of the 11 patients, 9
      cases resolved by the time of discharge, the 2 cases that persisted both were
      injuries to the facial nerve. Multivariate analysis using Bayesian shrinkage
      showed that after adjusting for all risk factors only IOM changes increased the
      risk of cranial nerve deficits (OR 38.47, 95% CI 7.73, 191.42). CONCLUSIONS:
      Cranial nerve injury is 38 times more likely in patients who experienced a change
      in IOM during CEA shunt. Future studies examining the effect of stretch and the
      degree of retraction on the CN might be more helpful in reducing cranial nerve
      deficits.

PMID- 25621711
TI  - Chiari malformation type 1.5 in male monozygotic twins: case report and
      literature review.

PMID- 25621712
TI  - Relapse of neuromyelitis optica during pregnancy--treatment options and
      literature review.

PMID- 25621713
TI  - Sinonasal morbidity following endoscopic endonasal skull base surgery.
AB  - Open transcranial surgery has long served as the traditional approach for
      resecting tumors and other lesions in the skull base. However, endoscopic
      endonasal skull base surgery (EESBS) has emerged as a credible alternative. This
      paper provides insight on the sinonasal morbidity in patients undergoing EESBS. A
      literature review was performed by searches of MEDLINE database to provide
      further insight on sinonasal morbidity associated with EESBS, with a particular
      focus on published incidence rates and patterns of complication. We identified
      only articles that reported the incidence of sinonasal morbidity and
      complications as the major outcome of the studies. The most common sinonasal
      morbidity symptoms are nasal crusting (50.8%), nasal discharge (40.4%), nasal
      airflow blockage (40.1%) followed by disturbances in olfaction (26.7%). The
      incidence of mucocele formation is 8%, and this is significantly increased in
      pediatric patients up to 25% (range, 14-50%). Epistaxis appears to be a rare
      event, often times not found in some case series. Some studies suggested less
      morbidity if the middle turbinate can be preserved, a finding that must be
      balanced with the need for sufficient exposure on larger cases. Sinonasal
      morbidity following endoscopic endonasal skull base surgery has the potential to
      adversely impact patient quality of life, with nasal crusting and discharge being
      the two most common symptoms. Morbidity signs and symptoms usually resolve within
      3-4 months, however symptoms can persist for longer with more complex surgeries.
      The rate of mucocele formation is higher in pediatric patients, with special
      attention required in graft positioning for this population in particular. 

PMID- 25621714
TI  - Micropatterning for the control of surface cavitation: visualization through high
      speed imaging.
AB  - For the first time, we apply a high-speed imaging technique to record the
      activity of acoustically driven cavitation bubbles (86 kHz) on micropatterned
      surfaces with hydrophobic and hydrophilic stripes. The width of the hydrophobic
      stripes lies between 3.5 and 115 MUm. This work provides the first direct
      visualization of the preferential location of bubbles on the hydrophobic areas of
      the patterns. The results confirm our previous prediction that surface cavitation
      strongly depends on the surface energy of the irradiated substrate. The
      observations show a remarkable effect of the stripe width on the size, movement,
      growth, splitting, and multiplying of the bubbles. The high-speed imaging also
      reveals that there is a minimal width of the hydrophobic stripes that allows
      bubble attraction and formation. Our observations are supported by a theoretical
      approach based on the forces acting on the bubbles. 

PMID- 25621715
TI  - The effect of medium structure complexity on the growth of Saccharomyces
      cerevisiae in gelatin-dextran systems.
AB  - As most food systems are (semi-)solid, the effect of food structure on bacterial
      growth has been widely acknowledged. However, studies on the growth dynamics of
      yeasts have neglected the effect of food structure. In this paper, the growth
      dynamics of the spoilage yeast Saccharomyces cerevisiae was investigated at 23.5 
      degrees C in broth, singular, homogeneous biopolymer systems and binary
      biopolymer systems with a heterogeneous microstructure. The biopolymers gelatin
      and dextran were used to introduce the different levels of structure. The
      metabolizing ability of gelatin and dextran by S. cerevisiae was examined. To
      study microbial behavior in the binary systems at the micro level, mixtures were
      imaged with confocal laser scanning microscopy (CLSM). Growth dynamics and
      microscopic images of S. cerevisiae were compared with those obtained for
      Escherichia coli in the same model system (Boons et al., 2014). Different phase
      separated, heterogeneous microstructures were obtained by changing the amount of
      added gelatin and dextran. Regardless of the microstructure, S. cerevisiae was
      preferentially located in the dextran phase. Metabolizing ability-tests indicated
      that gelatin could be consumed by S. cerevisiae but in the presence of glucose,
      no change in gelatin concentration was observed. No indication of dextran
      metabolizing ability was observed. When supplementing broth with gelatin or
      dextran alone, an enhanced growth rate and maximum cell density were observed.
      This enhancement was further increased by adding a second biopolymer, introducing
      a heterogeneous microstructure and hence increasing the medium structure
      complexity. The results obtained indicate that food structure complexity plays a
      significant role in the growth dynamics of S. cerevisiae, an important food
      spoiler.

PMID- 25621716
TI  - Isolation and characterization of psychrotolerant endospore-forming Sporosarcina
      species associated with minced fish meat (surimi).
AB  - We studied the changes of resident microbiota in surimi-minced fish meat-during
      heat-treatment and subsequent cold-storage via the sequencing of partial 16S rRNA
      gene. Raw surimi made from Alaska pollock, pike conger, and white croaker was
      contaminated with 10(4) to 10(6)CFU/g of various non-endospore-forming bacteria.
      Immediately after heat-treatment, the bacterial counts were significantly reduced
      to less than 1CFU/g, and only endospore-forming bacteria, identified as Bacillus
      species were retrieved. Subsequently, the bacterial counts increased up to 10 to
      10(5)CFU/g in the heated surimi after refrigerated storage at 5  degrees C for 2
      weeks or at 10  degrees C for 1 week. Most of the isolates from the refrigerated
      surimi were identified as Sporosarcina species. The Sporosarcina isolates have an
      increased ability to grow at 10  degrees C than the isolates related to the other
      endospore-forming bacteria, such as Bacillus, Lysinibacillus, and Paenibacillus
      species. Endospores of the Sporosarcina isolates were able to germinate and
      proliferate in a fish-paste product model system stored at 10  degrees C within 8
      days. In order to study the cold-adaptation mechanism of Sporosarcina species,
      the fatty acid composition of the isolates was analyzed. At the growth
      temperature of 10  degrees C, the proportions of unsaturated to saturated fatty
      acids and anteiso to iso fatty acids were higher than those at 28  degrees C. The
      alteration of the fatty acid composition suggests that Sporosarcina species adapt
      to cold by maintaining the fluidity of the cell membrane because unsaturated and
      anteiso fatty acids have lower melting points than saturated and iso fatty acids,
      respectively. We concluded that the endospores of Sporosarcina species are widely
      distributed in surimi, and that they can survive heat-treatment and proliferate
      during cold-storage in fish-paste products. Controlling Sporosarcina species
      would contribute to improving the quality of surimi product.

PMID- 25621718
TI  - Improved analysis of dissolved organic nitrogen in water via electrodialysis
      pretreatment.
AB  - This study evaluated electrodialysis (ED) for direct, accurate, and precise
      dissolved organic nitrogen (DON) analysis in water. Unlike conventional methods
      that calculate DON as the difference between total dissolved nitrogen (TDN) and
      dissolved inorganic nitrogen (DIN), we designed a compact ED reactor as a
      pretreatment tool that completely separates DIN from DON in water and then
      measures DON by equating DON to TDN. The experiments confirmed that the ED
      pretreatment process can achieve 99% removal of all three major DIN species
      (i.e., ammonia, nitrite, and nitrate) and an average recovery rate of 88% for an
      array of model DON compounds of varying characteristics (e.g., urea, amino acids,
      tripeptide, protein, and humic substances). Variations in nitrogen removal and
      recovery might be explained by a combined effect of molecular weight, acid
      dissociation ability (pK(a)), aromaticity, and ED reactor configurations. For
      model solutions with DIN/DON ratios varying from 1 to 10 mg-N/mg-N, the relative
      standard deviations in DON concentrations were considerably lower with ED
      pretreatment (<10%) than without pretreatment (47%). A survey of seven field
      samples, including lake water, tap water, and treated wastewater, also
      demonstrated the benefits of using ED pretreatment as compared with a
      conventional DON analysis method. Overall, this study provides evidence and
      mechanistic insight for a new DON detection method that uses ED pretreatment. The
      ED unit is robust for separating DIN and DON, and thus it may facilitate more
      frequent detection of DON and ultimately enhances understanding of DON issues in
      the environmental studies.

PMID- 25621717
TI  - Yeast population dynamics during prefermentative cold soak of Cabernet Sauvignon
      and Malbec wines.
AB  - Prefermentative cold soak is a widely used technique in red wine production, but
      the impact on the development of native yeast species is hardly described. The
      aim of this work was to analyse the dynamics and diversity of yeast populations
      during prefermentative cold soak in red wines. Three different temperatures (14
      +/- 1  degrees C; 8 +/- 1  degrees C and 2.5 +/- 1  degrees C) were used for
      prefermentative cold soak in Cabernet Sauvignon and Malbec grape musts.
      Saccharomyces and non-Saccharomyces populations during cold soak and alcoholic
      fermentation were analysed. In addition, the impact on chemical and sensory
      properties of the wines was examined. Yeast dynamics during prefermentative cold
      soak were temperature dependent. At 14 +/- 1  degrees C, the total yeast
      population progressively increased throughout the cold soak period. Conversely,
      at 2.5 +/- 1  degrees C, the yeast populations maintained stable during the same
      period. Prefermentative cold soak conducted at 14+/-1 degrees C favoured
      development of Hanseniospora uvarum and Candida zemplinina, whereas cold soak
      conducted at 8 +/- 1  degrees C favoured growth of Saccharomyces cerevisiae. At
      2.5 +/- 1  degrees C, no changes in yeast species were recorded. Acidity and
      bitterness, two sensory descriptors, appear to be related to wines produced with
      prefermentative cold soak carried out at 14 +/- 1  degrees C. This fact could be
      associated with the increase in non-Saccharomyces during the prefermentation
      stage. Our results emphasise the importance of the temperature as a determinant
      factor to allow an increase in non-Saccharomyces population during
      prefermentative cold soak and consequently to modify sensorial attributes of
      wines as well as their sensorial impact.

PMID- 25621719
TI  - Partial sleep deprivation does not alter processes involved in semantic word
      priming: event-related potential evidence.
AB  - Sleep deprivation has generally been observed to have a detrimental effect on
      tasks that require sustained attention for successful performance. It might
      however be possible to counter these effects by altering cognitive strategies. A
      recent semantic word priming study indicated that subjects used an effortful
      predictive-expectancy search of semantic memory following normal sleep, but
      changed to an automatic, effortless strategy following total sleep deprivation.
      Partial sleep deprivation occurs much more frequently than total sleep
      deprivation. The present study therefore employed a similar priming task
      following either 4h of sleep or following normal sleep. The purpose of the study
      was to determine whether partial sleep deprivation would also lead to a shift in
      cognitive strategy to compensate for an inability to sustain attention and
      effortful processing necessary for using the predicative expectancy strategy.
      Sixteen subjects were presented with word pairs, a prime and a target that were
      either strongly semantically associated (cat...dog), weakly associated
      (cow...barn) or not associated (apple...road). The subject's task was to
      determine if the target word was semantically associated to the prime. A strong
      priming effect was observed in both conditions. RTs were slower, accuracy lower,
      and N400 larger to unassociated targets, independent of the amount of sleep. The
      overall N400 did not differ as a function of sleep. The scalp distribution of the
      N400 was also similar following both normal sleep and sleep loss. There was thus
      little evidence of a difference in the processing of the target stimulus as a
      function of the amount sleep. Similarly, ERPs in the period between the onset of
      the prime and the subsequent target also did not differ between the normal sleep
      and sleep loss conditions. In contrast to total sleep deprivation, subjects
      therefore appeared to use a common predictive expectancy strategy in both
      conditions. This strategy does however require an effortful sustaining of
      attention, and may not have been entirely successful when sleep was restricted. A
      slight but significant decrease in accuracy was noted.

PMID- 25621720
TI  - Correction to cavity-enhanced absorption measurements across broad absorbance and
      reflectivity ranges.

PMID- 25621721
TI  - Student Expectations About Mental Health and Aging.
AB  - Drawing from stereotype embodiment theory this study contributes to existing
      literature by examining whether and how expectations regarding mental health and
      aging changed for students enrolled in an undergraduate gerontology course at a
      Canadian research university (N = 51). At the beginning and end of the course,
      data from an open-ended word association exercise and the Expectations Regarding
      Aging (ERA-12) survey was collected and later analyzed. Investigators used
      content analysis and quantization to examine the word association data and
      statistical tests to analyze the mental health subscale (ERA-MHS). Findings were
      integrated and presented in a convergence code matrix. Results show that overall
      participants had more favorable expectations over time; in particular, ERA-MHS
      scores indicated less favorable expectations at Time 1 (M = 48.86) than at Time 2
      (M = 65.36) significant at p < .01, while terms like "successful aging" increased
      and terms like "depressed" decreased. Findings have implications for geriatric
      mental health competencies of students in the health professions.

PMID- 25621722
TI  - Natural oxidation of a temperature series of biochars: opposite effect on the
      sorption of aromatic cationic herbicides.
AB  - The natural oxidation of biochar in the environment has been widely observed.
      However, its influence on the sorption of organic contaminants remains poorly
      understood. In the present study, a series of wood-based biochars prepared
      between 300 and 600 degrees C (referred to as BC300-BC600) was abiotically
      incubated for one year to examine the aging effect of the temperature series of
      biochars on their sorption of aromatic cationic herbicides (ACHs, paraquat and
      diquat) as well as a nonpolar reference adsorbate (naphthalene). One year of
      oxidation showed no obvious effect on the surface area, but distinct increases in
      the O/C elemental ratio, density of the surface groups and cation exchange
      capacity (CEC) were observed. Therefore, these properties were significantly
      affected by the charring temperature. After incubation, high-temperature biochars
      (BC500 and BC600) displayed a 14.1-36.3% decrease in the sorption (qm) of ACHs.
      The alteration of their sorption tendency was similar to the reduced sorption of
      naphthalene on oxidized biochars, in which the increased surface groups lowered
      the surface area accessible to adsorbates because of blockage by adsorbed water
      molecule clusters. Conversely, a pronounced increase of ACHs sorption by 121.7
      201.1% on the low-temperature biochar (BC300) was observed, presumably due to the
      increase of CEC values after oxidation. This result was further demonstrated by a
      significant linear relationship between the paraquat sorption (qm) and CEC values
      (R(2)=0.9895) of oxidized biochars. Interestingly, one year of oxidation
      simultaneously resulted in an enhanced sorption of paraquat and a reduced
      sorption of diquat on BC400, which indicated that the oxidation-induced sorption
      change of ACHs is a complex function of changes in the surface properties of the
      biochars as well as the molecular structure of the solute. 

PMID- 25621723
TI  - Effect of various carbon sources on biomass and lipid production of Chlorella
      vulgaris during nutrient sufficient and nitrogen starvation conditions.
AB  - In this research, a two-stage process consisting of cultivation in nutrient rich
      and nitrogen starvation conditions was employed to enhance lipid production in
      Chlorella vulgaris algal biomass. The effect of supplying different organic and
      inorganic carbon sources on cultivation behavior was investigated. During
      nutrient sufficient condition (stage I), the highest biomass productivity of
      0.158+/-0.011g/L/d was achieved by using sodium bicarbonate followed by 0.130+/
      0.013, 0.111+/-0.005 and 0.098+/-0.003g/L/d for sodium acetate, carbon dioxide
      and molasses, respectively. Cultivation under nitrogen starvation process (stage
      II) indicated that the lipid and fatty acid content increased continuously to a
      maximum value at day 2. Using carbon dioxide resulted in highest cell density,
      while using sodium acetate led to the highest fatty acid content. Molasses was
      not as effective as other carbon sources, but by taking into account its lower
      price, it can be considered as a suitable carbon source for algal lipid
      productivity. 

PMID- 25621724
TI  - Linking operation parameters and environmental variables to population dynamics
      of Mycolata in a membrane bioreactor.
AB  - The community structure and population dynamics of Mycolata were monitored in a
      full-scale membrane bioreactor during four experimental phases under changing
      operating and environmental conditions, by means of temperature-gradient gel
      electrophoresis of partial 16S-rRNA genes amplified from community DNA and RNA
      templates (total and active populations). Non-metric multidimensional scaling and
      BIO-ENV analyses demonstrated that population dynamics were mostly explained (30
      32%) by changes in the input of nutrients in the influent water and the
      accumulation of biomass in the bioreactors, while the influence of hydraulic and
      solid retention times, temperature and F/M ratio was minor. Significant
      correlations were observed between particular Mycolata phylotypes and one or more
      variables, contributing information for the prediction of their abundance and
      activity under changing conditions. Fingerprinting and multivariate analyses
      demonstrated that two foaming episodes, recorded at temperatures <20 degrees C,
      were connected to the increase of the relative abundance of Mycolata unrelated to
      Gordonia amarae. 

PMID- 25621725
TI  - The feasibility of using complex wastewater from a monosodium glutamate factory
      to cultivate Spirulina subsalsa and accumulate biochemical composition.
AB  - This paper is mainly observations on the growth and biomass accumulation of
      Spirulina subsalsa in modified Zarrouk medium supplemented with complex
      wastewater (CW, from a monosodium glutamate factory) in different concentrations.
      High ammonia in 75% and 100% CW inhibits algae growth, but maximum biomass
      production (2.86mgL(-1)) was obtained in 25% CW (concentration of CW in medium
      was 25%). Different CW concentration promoted biomass composition accumulation at
      different degrees, 41% of protein content in 25% CW and 18% of carbohydrate in
      50% CW. In terms of economy, a concentration of 25% CW was suitable for protein
      production and 50% for lipid and carbohydrate production. These results suggested
      that CW is a feasible replacement in part for cultivation of S. subsalsa to
      economize input of water and nutrients. 

PMID- 25621726
TI  - Continuous lactose fermentation by Clostridium acetobutylicum--assessment of
      solventogenic kinetics.
AB  - This work reports the results of a series of tests on the specific butanol
      production rate by Clostridium acetobutylicum continuous cultures. The tests were
      carried out using lactose as carbon source to mimic cheese-whey. A continuous
      stirred tank reactor equipped with a microfiltration unit was used. The dilution
      rate (D) ranged between 0.02 and 0.15h(-1) and the ratio R of the permeate stream
      rate to the stream fed to the reactor ranged between 14% and 95%. For each set of
      D and R values, the continuous cultures were characterized in terms of
      concentration of cells, acids and solvents. Results were processed to assess the
      concentration of acidogenic cells, solventogenic cells, spores and the specific
      butanol production rate. The max butanol productivity was 0.5gL(-1)h(-1) at
      D=0.1h(-1) and R=95%. The butanol productivity referred to solventogenic cells
      was expressed as a function of concentration of lactose, acids and butanol. 

PMID- 25621727
TI  - Enhancement in the enzymatic digestibility of hybrid poplar with poor residual
      hemicelluloses after Na2SO3 pretreatment.
AB  - The aim of this work was to illustrate the contributions of delignification and
      the introduced sulfonic groups on the enzymatic digestibility of the Na2SO3
      pretreated hybrid poplar with poor residual hemicelluloses (HPPRH). The higher
      the content of the introduced sulfonic group in the pretreated HPPRH was, the
      higher its enzymatic digestibility could be achieved. Delignification was
      favorable to increasing the content of sulfonic group in the pretreated HPPRH.
      The introduced sulfonic group contributed much more to the total glucose yield at
      low level of residual lignin. The introduced sulfonic groups could contribute
      17.30% of total glucose yield (92.70%) and delignification could do 38.43% of it.
      Meanwhile, the delignification rate and the sulfonic group content in the
      pretreated HPRH were 59.88% and 283.51mmolkg(-1) lignin, respectively. Therefore,
      the sulfonic group introduced on the pretreated lignocellulosics could improve
      the enzymatic digestibility and make the sulfite process effective. 

PMID- 25621728
TI  - H2CHXdedpa and H4CHXoctapa-chiral acyclic chelating ligands for (67/68)Ga and
      (111)In radiopharmaceuticals.
AB  - The chiral acyclic ligands H2CHXdedpa (N4O2), H2CHXdedpa-bb (N4O2), and
      H4CHXoctapa (N4O4) (CHX = cyclohexyl/cyclohexane, H2dedpa = 1,2-[[6-carboxy
      pyridin-2-yl]-methylamino]ethane, bb = N,N'-dibenzylated, H4octapa = N,N'-bis(6
      carboxy-2-pyridylmethyl)-ethylenediamine-N,N'-diacetic acid) were synthesized,
      complexed with Ga(III) and/or In(III), and evaluated for their potential as
      chelating agents in radiopharmaceutical applications. The ligands were compared
      to the previously studied hexadentate H2dedpa and octadentate H4octapa ligands to
      determine the effect adding a chiral 1R,2R-trans-cyclohexane to replace the
      ethylenediamine backbone would have on metal complex stability and radiolabeling
      kinetics. It was found that [Ga(CHXdedpa)](+) showed very similar properties to
      those of [Ga(dedpa)](+), with only one isomer in solution observed by NMR
      spectroscopy, and minimal structural changes in the solid-state X-ray structure.
      Like [Ga(dedpa)](+), [Ga(CHXdedpa)](+) exhibited exceptionally high thermodynamic
      stability constants (log KML = 28.11(8)), and the chelate retained the ability to
      label (67)Ga quantitatively in 10 min at room temperature at ligand
      concentrations of 1 * 10(-5) M. In vitro kinetic inertness assays demonstrated
      the [(67)Ga(CHXdedpa)](+) complex to be more stable than [(67)Ga(dedpa)](+) in a
      human serum competition, with 90.5% and 77.8% of (67)Ga remaining chelate-bound
      after 2 h, respectively. Preliminary coordination studies of H4CHXoctapa with
      In(III) demonstrated [In(CHXoctapa)](-) to have an equivalently high
      thermodynamically stable constant as [In(octapa)](-), with log KML values of
      27.16(9) and 26.76(14), respectively. The [(111)In(CHXoctapa)](-) complex showed
      exceptionally high in vitro kinetic inertness over 120 h in human serum,
      comparing well with previously reported [(111)In(octapa)](-) values, and an
      improved stability compared to the current industry "gold standards" 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and
      diethylenetriaminepentaacetic acid (DTPA). Initial investigations reveal that the
      chiral acyclic hexadentate H2CHXdedpa and octadentate H4CHXoctapa ligands are
      ideal candidates for radiopharmaceutical elaboration of gallium or indium
      isotopes, respectively. 

PMID- 25621729
TI  - Selection of multiple agonist antibodies from intracellular combinatorial
      libraries reveals that cellular receptors are functionally pleiotropic.
AB  - The main purpose of this perspective is to build on the unexpected outcomes of
      previous laboratory experiments using antibody agonists to raise questions
      concerning how activation of a given receptor can be involved in inducing
      differentiation of cells along different pathways some of which may even derive
      from different lineages. While not yet answered, the question illustrates how the
      advent of agonists not present in nature may give a different dimension to the
      important problem of signal transduction. Thus, if one studies a natural agonist
      receptor system one can learn details about its signal transduction pathway.
      However, if one has a set of orthogonal agonists, one may learn about the yet
      undiscovered potential of the system that, in the end, may necessitate
      refinements to the currently used models. Thus, we wonder why receptors
      conventionally linked to a given pathway induce a different pattern of
      differentiation when agonized in another way. 

PMID- 25621730
TI  - PNA-encoded chemical libraries.
AB  - Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded
      libraries have provided a powerful new paradigm for library synthesis and ligand
      discovery. PNA-encoding stands out for its compatibility with standard solid
      phase synthesis and the technology has been used to prepare libraries of
      peptides, heterocycles and glycoconjugates. Different screening formats have now
      been reported including selection-based and microarray-based methods that have
      yielded specific ligands against diverse target classes including membrane
      receptors, lectins and challenging targets such as Hsp70. 

PMID- 25621731
TI  - Psychometric properties of the Body Checking Questionnaire in college women.
AB  - While the Body Checking Questionnaire (BCQ; Reas et al., 2002) is the most
      commonly-used measure of body checking behaviors, findings on the factor
      structure in nonclinical samples are mixed. This study investigated the factor
      structure and psychometric properties of the BCQ among nonclinical college women.
      In Study 1 (n=326), an exploratory factor analysis indicated factors
      corresponding to (a) behavioral and (b) visual checking. In Study 2 (n=1013), a
      confirmatory factor analysis revealed adequate fit for these factors, better than
      the original or total score solutions. Scales based upon the two factors
      demonstrated good internal consistency, convergent validity with measures of
      eating pathology, and sensitivity for detecting at-risk eating pathology. Results
      suggest an alternate two-factor solution that differs from the original three
      factor solution. 

PMID- 25621732
TI  - Panchromatic luminescence from julolidine dyes exhibiting excited state
      intramolecular proton transfer.
AB  - The preparation and the photophysical behaviour of novel julolidine derivatives
      designed for displaying excited state intramolecular proton transfer (ESIPT) are
      reported. These dyes exhibit panchromatic photoluminescence covering the whole
      visible spectral range, both in organic solvents and in the solid state. 

PMID- 25621733
TI  - Acetylome analysis reveals the involvement of lysine acetylation in
      photosynthesis and carbon metabolism in the model cyanobacterium Synechocystis
      sp. PCC 6803.
AB  - Cyanobacteria are the oldest known life form inhabiting Earth and the only
      prokaryotes capable of performing oxygenic photosynthesis. Synechocystis sp. PCC
      6803 (Synechocystis) is a model cyanobacterium used extensively in research on
      photosynthesis and environmental adaptation. Posttranslational protein
      modification by lysine acetylation plays a critical regulatory role in both
      eukaryotes and prokaryotes; however, its extent and function in cyanobacteria
      remain unexplored. Herein, we performed a global acetylome analysis on
      Synechocystis through peptide prefractionation, antibody enrichment, and high
      accuracy LC-MS/MS analysis; identified 776 acetylation sites on 513 acetylated
      proteins; and functionally categorized them into an interaction map showing their
      involvement in various biological processes. Consistent with previous reports, a
      large fraction of the acetylation sites are present on proteins involved in
      cellular metabolism. Interestingly, for the first time, many proteins involved in
      photosynthesis, including the subunits of phycocyanin (CpcA, CpcB, CpcC, and
      CpcG) and allophycocyanin (ApcA, ApcB, ApcD, ApcE, and ApcF), were found to be
      lysine acetylated, suggesting that lysine acetylation may play regulatory roles
      in the photosynthesis process. Six identified acetylated proteins associated with
      photosynthesis and carbon metabolism were further validated by
      immunoprecipitation and Western blotting. Our data provide the first global
      survey of lysine acetylation in cyanobacteria and reveal previously unappreciated
      roles of lysine acetylation in the regulation of photosynthesis. The provided
      data set may serve as an important resource for the functional analysis of lysine
      acetylation in cyanobacteria and facilitate the elucidation of the entire
      metabolic networks and photosynthesis process in this model cyanobacterium. 

PMID- 25621734
TI  - An electrochemical peptide cleavage-based biosensor for prostate specific antigen
      detection via host-guest interaction between ferrocene and beta-cyclodextrin.
AB  - Here we have developed a "signal-on" peptide cleavage-based assay to directly
      transduce the peptide cleavage events into electrochemical signals via the host
      guest interaction between ferrocene (Fc) and beta-cyclodextrin (beta-CD) for
      prostate specific antigen (PSA) detection. 

PMID- 25621735
TI  - Tuning temperature responsive poly(2-alkyl-2-oxazoline)s by supramolecular host
      guest interactions.
AB  - A poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)] random copolymer was
      synthesized and its thermoresponsive behavior in aqueous solution modulated by
      the addition of different supramolecular host molecules. The macrocycles formed
      inclusion complexes with the nonyl aliphatic side-chains present in the
      copolymer, increasing its cloud point temperature. The extent of this temperature
      shift was found to depend on the cavitand concentration and on the strength of
      the host-guest complexation. The cloud point temperature could be tuned in an
      unprecedented wide range of 30 K by supramolecular interactions. Since the
      temperature-induced breakage of the inclusion complexes constitutes the driving
      force for the copolymer phase transition, the shift in cloud point temperature
      could be utilized to estimate the association constant of the nonyl side chains
      with the cavitands. 

PMID- 25621736
TI  - Inubosins A, B, and C are acridine alkaloids isolated from a culture of
      Streptomyces sp. IFM 11440 with Ngn2 promoter activity.
AB  - Three new acridine alkaloids, inubosins A (1), B (2), and C (3), were isolated
      from an extract of a culture of Streptomyces sp. IFM 11440 using bioassay-guided
      fractionation. Neurogenin2 (Ngn2) is an activator-type basic helix-loop-helix
      transcription factor that promotes neural stem cell differentiation. Using cell
      based Ngn2 promoter activity-guided screening, Streptomyces sp. IFM 11440 was
      found to induce Ngn2 promoter activity. The structures of 1-3 were established
      using spectroscopic methods, including 1D- and 2D-NMR measurements. Inubosin B
      (2) showed potent Ngn2 promoter activity. Moreover, inubosin B (2) increased mRNA
      expression of genes related to neural stem cell differentiation. 

PMID- 25621737
TI  - Nitrogen stable isotope composition (delta15N) of vehicle-emitted NOx.
AB  - The nitrogen stable isotope ratio of NOx (delta(15)N-NOx) has been proposed as a
      regional indicator for NOx source partitioning; however, knowledge of delta(15)N
      values from various NOx emission sources is limited. This study presents a
      detailed analysis of delta(15)N-NOx emitted from vehicle exhaust, the largest
      source of anthropogenic NOx. To accomplish this, NOx was collected from 26
      different vehicles, including gasoline and diesel-powered engines, using a
      modification of a NOx collection method used by the United States Environmental
      Protection Agency, and delta(15)N-NOx was analyzed. The vehicles sampled in this
      study emitted delta(15)N-NOx values ranging from -19.1 to 9.80/00 that negatively
      correlated with the emitted NOx concentrations (8.5 to 286 ppm) and vehicle run
      time because of kinetic isotope fractionation effects associated with the
      catalytic reduction of NOx. A model for determining the mass-weighted delta(15)N
      NOx from vehicle exhaust was constructed on the basis of average commute times,
      and the model estimates an average value of -2.5 +/- 1.50/00, with slight
      regional variations. As technology improvements in catalytic converters reduce
      cold-start emissions in the future, it is likely to increase current delta(15)N
      NOx values emitted from vehicles. 

PMID- 25621738
TI  - Force nanoscopy of hydrophobic interactions in the fungal pathogen Candida
      glabrata.
AB  - Candida glabrata is an opportunistic human fungal pathogen which binds to
      surfaces mainly through the Epa family of cell adhesion proteins. While some Epa
      proteins mediate specific lectin-like interactions with human epithelial cells,
      others promote adhesion and biofilm formation on plastic surfaces via nonspecific
      interactions that are not yet elucidated. We report the measurement of
      hydrophobic forces engaged in Epa6-mediated cell adhesion by means of atomic
      force microscopy (AFM). Using single-cell force spectroscopy, we found that C.
      glabrata wild-type (WT) cells attach to hydrophobic surfaces via strongly
      adhesive macromolecular bonds, while mutant cells impaired in Epa6 expression are
      weakly adhesive. Nanoscale mapping of yeast cells using AFM tips functionalized
      with hydrophobic groups shows that Epa6 is massively exposed on WT cells and
      conveys strong hydrophobic properties to the cell surface. Our results
      demonstrate that Epa6 mediates strong hydrophobic interactions, thereby providing
      a molecular basis for the ability of this adhesin to drive biofilm formation on
      abiotic surfaces. 

PMID- 25621739
TI  - Enhancing Bidirectional Electron Transfer of Shewanella oneidensis by a Synthetic
      Flavin Pathway.
AB  - Flavins regulate the rate and direction of extracellular electron transfer (EET)
      in Shewanella oneidensis. However, low concentration of endogenously secreted
      flavins by the wild-type S. oneidensis MR-1 limits its EET efficiency in
      bioelectrochemical systems (BES). Herein, a synthetic flavin biosynthesis pathway
      from Bacillus subtilis was heterologously expressed in S. oneidensis MR-1,
      resulting in ~25.7 times' increase in secreted flavin concentration. This
      synthetic flavin module enabled enhanced bidirectional EET rate of MR-1, in which
      its maximum power output in microbial fuel cells increased ~13.2 times (from 16.4
      to 233.0 mW/m(2)), and the inward current increased ~15.5 times (from 15.5 to
      255.3 MUA/cm(2)). 

PMID- 25621740
TI  - Thermodynamic mapping of effector protein interfaces with RalA and RalB.
AB  - RalA and RalB are members of the Ras family of small G proteins and are activated
      downstream of Ras via RalGEFs. The RalGEF-Ral axis represents one of the major
      effector pathways controlled by Ras and as such is an important pharmacological
      target. RalA and RalB are approximately 80% identical at the amino acid level;
      despite this, they have distinct roles both in normal cells and in the disease
      state. We have used our structure of RalB-RLIP76 to guide an analysis of Ral
      effector interaction interfaces, creating panels of mutant proteins to probe the
      energetics of these interactions. The data provide a physical mechanism that
      underpins the effector selective mutations commonly employed to dissect Ral G
      protein function. Comparing the energetic landscape of the RalB-RLIP76 and RalB
      Sec5 complexes reveals mutations in RalB that lead to differential binding of the
      two effector proteins. A panel of RLIP76 mutants was used to probe the
      interaction between RLIP76 and RalA and -B. Despite 100% sequence identity in the
      RalA and -B contact residues with RLIP76, differences still exist in the
      energetic profiles of the two complexes. Therefore, we have revealed properties
      that may account for some of the functional separation observed with RalA and
      RalB at the cellular level. Our mutations, in both the Ral isoforms and RLIP76,
      provide new tools that can be employed to parse the complex biology of Ral G
      protein signaling networks. The combination of these thermodynamic and structural
      data can also guide efforts to ablate RalA and -B activity with small molecules
      and peptides. 

PMID- 25621741
TI  - When does money matter most? Examining the association between income and life
      satisfaction over the life course.
AB  - Previous research shows that the correlation between income and life satisfaction
      is small to medium in size. We hypothesized that income may mean different things
      to people at different ages and, therefore, that the association between income
      and life satisfaction may vary at different points in the life course. We tested
      this hypothesis in 3 nationally representative panel studies. Multilevel modeling
      techniques were used to test whether age moderated both the within- and between
      person associations. Consistent with past research, we found that individuals who
      earned more on average and individuals who earned more over time reported higher
      levels of life satisfaction. Importantly, these effects were strongest for
      midlife individuals (those in their 30s-50s) as compared with individuals who
      were younger or older.

PMID- 25621742
TI  - A review and meta-analysis of age-based stereotype threat: negative stereotypes,
      not facts, do the damage.
AB  - Stereotype threat effects arise when an individual feels at risk of confirming a
      negative stereotype about their group and consequently underperforms on
      stereotype relevant tasks (Steele, 2010). Among older people, underperformance
      across cognitive and physical tasks is hypothesized to result from age-based
      stereotype threat (ABST) because of negative age-stereotypes regarding older
      adults' competence. The present review and meta-analyses examine 22 published and
      10 unpublished articles, including 82 effect sizes (N = 3882) investigating ABST
      on older people's (Mage = 69.5) performance. The analysis revealed a significant
      small-to-medium effect of ABST (d = .28) and important moderators of the effect
      size. Specifically, older adults are more vulnerable to ABST when (a) stereotype
      based rather than fact-based manipulations are used (d = .52); (b) when
      performance is tested using cognitive measures (d = .36); and (c) occurs reliably
      when the dependent variable is measured proximally to the manipulation. The
      review raises important theoretical and methodological issues, and areas for
      future research.

PMID- 25621744
TI  - Predatory publishing: what nurse executives need to know.
AB  - Editors attending the 2014 meeting of the International Academy of Nursing
      Editors have coalesced to provide information to our readers regarding a recent
      trend in the publishing world, predatory publishing.

PMID- 25621743
TI  - Social resource correlates of levels and time-to-death-related changes in late
      life affect.
AB  - Little is known regarding how well psychosocial resources that promote well-being
      continue to correlate with affect into very late life. We examined social
      resource correlates of levels and time-to-death related changes in affect balance
      (an index of affective positivity) over 19 years among 1,297 by now deceased
      participants (aged 69 to 103 at first assessment, M = 80 years; 36% women) from
      the Australian Longitudinal Study of Aging. A steeper decline in affect balance
      was evident over a time-to-death metric compared with chronological age.
      Separating time-varying social resource predictors into between- and within
      person components revealed several associations with level of affect balance,
      controlling for age at death, gender, functional disability, and global
      cognition. Between-person associations revealed that individuals who were more
      satisfied with family, and more socially active, expressed greater positivity
      compared with those who were less satisfied, and less socially active. Within
      person associations indicated that participants reported higher positivity on
      occasions when they were more socially active. In addition, lower affect balance
      was associated with more frequent contact with children. Our results suggest that
      social engagement and satisfying relationships confer benefits for affective well
      being that are retained into late life. However, our findings do not provide
      evidence to indicate that social resources protect against terminal decline in
      well-being.

PMID- 25621745
TI  - Moving forward: lessons from unplanned change.
AB  - The article focuses on the concept of unplanned change in a large tertiary
      facility in Texas related to the 1st Ebola patient to be diagnosed in the United
      States. The chief nurse executive relates the general reactions, impacts, and
      challenges faced in this unprecedented event. 

PMID- 25621746
TI  - Developing leadership talent: a statewide nurse leader mentorship program.
AB  - Nurse leaders continue to seek support programs essential for advancement to
      senior roles. Providing such support presents a challenge for the future of
      nursing in the state of New Jersey and on a national level. This article
      discusses the creation of a mentorship program by the Organization of Nurse
      Executives of New Jersey (ONE NJ). In recognition of the program, which has
      contributed to the advancement of New Jersey nursing leadership, the ONE NJ
      received the 2014 American Organization of Nurse Executives Chapter Achievement
      Award.

PMID- 25621747
TI  - Keeping patients safe: antibiotic resistance and the role of nurse executives in
      antibiotic stewardship.
AB  - In this column, the authors discuss the issue of antibiotic resistance,
      components of a program of antibiotic stewardship, and the role of the nurse
      executive in leading and supporting these efforts. 

PMID- 25621748
TI  - Sustainability of an innovation to support and respond to persons with behaviors
      related to dementia and delirium.
AB  - Gentle Persuasive Approaches (GPA) in Dementia Care, a program designed for staff
      caring for patients in long-term care who exhibit challenging behaviors, was
      implemented and has been sustained in an acute care setting. Outcomes include
      fewer codes indicating violent situations, a reduction in physical restraint and
      sitter use, and fewer reports of safety incidents involving agitated patients. In
      this article, we describe the innovation (GPA) and the strategies used to sustain
      its successful implementation. 

PMID- 25621749
TI  - Part 1: Evidence-based facility design using Transforming Care at the Bedside
      principles.
AB  - An academic hospital used Transforming Care at the Bedside (TCAB) principles as
      the framework for generating evidence-based recommendations for the design of an
      expansion of the current hospital. The interdisciplinary team used the table of
      evidence-based data to advocate for a patient- and family-centered, safe, and
      positive work environment. A nurse project manager acted as liaison between the
      TCAB design team, architects, and facilities and design consultants. Part 2 of
      this series describes project evaluation outcomes. 

PMID- 25621750
TI  - Part 2: Evaluation and outcomes of an evidence-based facility design project.
AB  - Based on the work of a TCAB facility design team at an academic hospital (part
      1), an evaluation project was implemented to measure RN work environment
      perceptions, work activity sampling, and steps walked on 6 units moving into a
      new acute care pavilion. Pre and post data reported significant nurse
      satisfaction post move with the new work environment. Workflow sampling data did
      not reflect significant changes; the pedometer device used to measure nurse steps
      proved unreliable. Project evaluation data are reported. 

PMID- 25621751
TI  - How hospitals view unit-level nurse turnover data collection: analysis of a
      hospital survey.
AB  - OBJECTIVE: The objectives of this study were to examine the quality of unit-level
      nurse turnover data collection among the National Database of Nursing Quality
      Indicators hospitals and to identify the burdens of collecting such data.
      BACKGROUND: Tracking and managing nurse turnover at the unit level are critical
      for administrators who determine managerial strategies. Little is known about the
      quality of and burdens of unit-level turnover data collection. METHODS: Surveys
      from 178 hospitals were analyzed descriptively. RESULTS: Most hospitals strongly
      agreed or agreed with the quality of unit-level turnover data collection.
      Hospitals identified the burdens of additional time and resources needed for unit
      level turnover data collection and the difficulty of obtaining specific reasons
      for turnover. CONCLUSIONS: Collecting unit-level nurse turnover data can be
      important and useful for administrators to improve nurse retention, workforce
      stability, and quality of care. We suggest that the advantages of unit-level
      nurse turnover data and reports can overcome the identified burdens.

PMID- 25621752
TI  - Nursing professional capital: a qualitative analysis.
AB  - OBJECTIVE: The objective of this study was to offer qualitative support for the
      assertion that nurses possess professional capital. BACKGROUND: Nurses embrace
      professional standards and tenets that have been measured as trust and ethics. By
      understanding forms of capital and combining quantitative public-opinion surveys
      and our qualitative findings, a case can be made that nurses possess professional
      capital. METHOD: This was a focused review of existing interview data and was
      conducted using inductive content analysis. FINDINGS: Patients provided
      unsolicited accounts of trust and positive regard for their nurses. CONCLUSION:
      Evidence supports that in combination with trust and positive regard, nurses
      possess professional capital. Nurses should judiciously use their professional
      capital to impact institutional, political, and economic policy.

PMID- 25621753
TI  - Effects of nursing position on transformational leadership practices.
AB  - OBJECTIVE: This study sought to identify significant differences in nursing
      leadership strengths by position title. BACKGROUND: Recent reports show aspects
      of transformational leadership (TL) related to position, age, and educational
      level. This study focuses on differentiating the strength of leadership practices
      across the range of nursing management positions. METHODS: The Leadership
      Practices Inventory-Self-assessment survey, and a variety of demographic
      questions, were used to anonymously poll voluntary members of the Association of
      California Nurse Leaders. RESULTS: Nursing positions of director level and above
      were strongest in leadership practices. Those at manager and below were
      identified as needing additional leadership development. LPI-S subscales Enable
      Others to Act and Model the Way were strongest. CONCLUSION: Those at the manager
      level and below will benefit most from additional education and training. Even
      upper levels of management would gain from enhancing the LPI practices of
      Challenge the Process and Inspire a Shared Vision.

PMID- 25621754
TI  - The development of sex category representation in infancy: matching of faces and
      bodies.
AB  - Sex is a significant social category, and adults derive information about it from
      both faces and bodies. Research indicates that young infants process sex category
      information in faces. However, no prior study has examined whether infants derive
      sex categories from bodies and match faces and bodies in terms of sex. In the
      current study, 5-month-olds exhibited a preference between sex congruent (face
      and body of the same sex) versus sex-incongruent (face and body belonging to
      different genders) images. In contrast, 3.5-month-olds failed to exhibit a
      preference. Thus, 5-month-olds process sex information from bodies and match it
      to facial information. However, younger infants' failure to match suggests that
      there is a developmental change between 3.5 and 5 months of age in the processing
      of sex categories. These results indicate that rapid developmental changes lead
      to fairly sophisticated social information processing quite early in life.

PMID- 25621755
TI  - A dual-process approach to the role of mother's implicit and explicit attitudes
      toward their child in parenting models.
AB  - Extending dual process frameworks of cognition to a novel domain, the present
      study examined how mothers' explicit and implicit attitudes about her child may
      operate in models of parenting. To assess implicit attitudes, two separate
      studies were conducted using the same child-focused Go/No-go Association Task
      (GNAT-Child). In Study 1, model analyses revealed that maternal implicit
      attitudes about her child were associated with maternal sensitive/responsive
      caregiving behaviors concurrently and predicted changes in caregiving over time
      In Study 2, challenging child behaviors were uniquely linked to maternal implicit
      and explicit attitudes. In turn, maternal implicit attitudes were associated with
      observational assessments of maternal sensitivity. Results underscore the
      potential for a dual-process approach to inform models of parenting and child
      behavior.

PMID- 25621758
TI  - Characterizing lifespan development of three aspects of coherence in life
      narratives: a cohort-sequential study.
AB  - The ability to narrate stories and a synchronic self-concept develop in the pre-
      and primary school years. Life story theory proposes that both developments
      extend to an even later developmental stage, that is, to adolescents' acquisition
      of a coherent life story. Cross-sectional evidence supports the emergence of a
      life story in adolescence, but is mixed in terms of later life span development.
      The present study examines longitudinally the development of global coherence in
      life narratives across almost the entire life span. Starting in 2003, a total of
      172 participants narrated their lives over the course of 8 years (aged 16, 20,
      24, 28, 44, and 69 when last tested) resulting in up to 4 life narratives per
      person. Three aspects of global life narrative coherence--temporal, causal
      motivational, and thematic coherence--were measured with global ratings and
      predicted by their respective textual indicators. Children lacked most aspects of
      global coherence. Almost all indicators of temporal and causal-motivational
      coherence increased substantially across adolescence up to early adulthood, as
      did thematic coherence, which continued to develop throughout middle adulthood.

PMID- 25621756
TI  - Vocabulary, syntax, and narrative development in typically developing children
      and children with early unilateral brain injury: early parental talk about the
      "there-and-then" matters.
AB  - This study examines the role of a particular kind of linguistic input--talk about
      the past and future, pretend, and explanations, that is, talk that is
      decontextualized--in the development of vocabulary, syntax, and narrative skill
      in typically developing (TD) children and children with pre- or perinatal brain
      injury (BI). Decontextualized talk has been shown to be particularly effective in
      predicting children's language skills, but it is not clear why. We first explored
      the nature of parent decontextualized talk and found it to be linguistically
      richer than contextualized talk in parents of both TD and BI children. We then
      found, again for both groups, that parent decontextualized talk at child age 30
      months was a significant predictor of child vocabulary, syntax, and narrative
      performance at kindergarten, above and beyond the child's own early language
      skills, parent contextualized talk and demographic factors. Decontextualized talk
      played a larger role in predicting kindergarten syntax and narrative outcomes for
      children with lower syntax and narrative skill at age 30 months, and also a
      larger role in predicting kindergarten narrative outcomes for children with BI
      than for TD children. The difference between the 2 groups stemmed primarily from
      the fact that children with BI had lower narrative (but not vocabulary or syntax)
      scores than TD children. When the 2 groups were matched in terms of narrative
      skill at kindergarten, the impact that decontextualized talk had on narrative
      skill did not differ for children with BI and for TD children. Decontextualized
      talk is thus a strong predictor of later language skill for all children, but may
      be particularly potent for children at the lower-end of the distribution for
      language skill. The findings also suggest that variability in the language
      development of children with BI is influenced not only by the biological
      characteristics of their lesions, but also by the language input they receive.

PMID- 25621757
TI  - Nonresident fatherhood and adolescent sexual behavior: a comparison of siblings
      approach.
AB  - Although voluminous research has linked nonresident fatherhood to riskier sexual
      behavior in adolescence, including earlier sexual debut, neither the causality of
      that link nor the mechanism accounting for it has been well-established. Using
      data from the National Longitudinal Survey of Youth, 1979-the Young Adult Survey
      (CNLSY-YA), the present study addresses both questions by comparing the sexual
      development of siblings discordant for age at father departure from the home and
      examining results across behavioral (age at first intercourse), biological
      (pubertal timing), and cognitive (attitudes about childbearing and marriage)
      sexual outcomes (N = 5,542). Findings indicate that nonresident fatherhood,
      beginning either at birth or during middle childhood, leads to an earlier sexual
      debut for girls, but not for boys, an effect likely explained by weak parental
      monitoring rather than an accelerated reproductive strategy.

PMID- 25621759
TI  - Generation of ensembles of individually resolvable nitrogen vacancies using
      nanometer-scale apertures in ultrahigh-aspect ratio planar implantation masks.
AB  - A central challenge in developing magnetically coupled quantum registers in
      diamond is the fabrication of nitrogen vacancy (NV) centers with localization
      below ~20 nm to enable fast dipolar interaction compared to the NV decoherence
      rate. Here, we demonstrate the targeted, high throughput formation of NV centers
      using masks with a thickness of 270 nm and feature sizes down to ~1 nm. Super
      resolution imaging resolves NVs with a full-width maximum distribution of 26 +/-
      7 nm and a distribution of NV-NV separations of 16 +/- 5 nm. 

PMID- 25621761
TI  - Persistence of IgG antibody following routine infant immunization with the 7
      valent pneumococcal conjugate vaccine.
AB  - BACKGROUND: Pneumococcal conjugate vaccine (PCV) induces protective anticapsular
      IgG, which mediates disease immunity. IgG persistence may influence long-term
      protection. METHODS: An observational, prospective, longitudinal study of
      nasopharyngeal carriage among American Indian households from 2006 to 2008
      evaluated long-term immunogenicity of 7-valent PCV (PCV7). Children unimmunized
      with PCV were age-matched to those PCV7 immunized at least 4 years prior (ratio
      1:3 or 1:4). Blood collected at the final study visit was analyzed for PCV7
      serotype IgG (enzyme-linked immunosorbent assay) and for functional activity
      (multiplex-opsonophagocytic assay) for serotypes 4, 6B, 14 and 23F. Geometric
      mean concentrations (GMCs), titers (GMTs) and the odds of serotype-specific IgG
      >=0.35 MUg/mL were compared according to immunization status using a matched
      regression approach. RESULTS: Eight unimmunized and 28 immunized children age
      matched at the time of serum collection (mean age: 7.9 years) were included.
      Serotype-specific GMCs, GMTs and proportions above the correlate of protection
      did not differ between the groups except for serotypes 14 and 23F. Serotype 14
      GMCs (immunized 0.7 vs. unimmunized 0.2; P = 0.02) and serotype 23F GMTs
      (immunized 388.3 vs. unimmunized 47.8; P = 0.03) were significantly higher among
      immunized children. IgG concentrations and functional titers among immunized
      children were strongly correlated for serotypes 4 (r = 0.78; P <= 0.001) and 14
      (r = 0.52; P <= 0.01). CONCLUSIONS: PCV serotype-specific IgG concentrations 4
      years following PCV vaccination do not persist above natural levels for most
      serotypes. Exposure to pneumococcus may be critical in maintaining persistent
      serotype-specific IgG; the elimination of circulating vaccine type pneumococci by
      PCV may have effects on long-term immunity.

PMID- 25621762
TI  - Effectiveness of routine and booster pertussis vaccination in children and
      adolescents, federal state of Brandenburg, Germany, 2002-2012.
AB  - BACKGROUND: In Germany, whole-cell pertussis vaccines were rapidly replaced by
      high-concentration acellular pertussis-containing vaccines (3+1 doses from 2
      months of age) starting in 1995. Boosters were recommended for 9- to 17-year-olds
      (2000) and for 5- to 6-year-olds (2006). Pertussis incidence remains high despite
      rising vaccination coverage (VC). Therefore, we analyzed VC and vaccine
      effectiveness (VE) in the federal state of Brandenburg. METHODS: In a stratified
      case-cohort analysis, we compared VC of reported pertussis cases with VC assessed
      in schools and kindergartens in the following strata: Children aged 2-3 years
      born 2005-2009 (toddlers), 5-7 years born 1995-2006 (pre-schoolers) and 15-16
      years born 1995-1996 (adolescents). We calculated VE for primary and booster
      vaccination using Poisson regression. RESULTS: Four-dose VE decreased from 96.9%
      in toddlers [95% confidence interval (CI): 72.2-99.3] to 87.8% in pre-schoolers
      (95% CI: 79.7-92.7) to 81.7% in adolescents (95% CI: 40.6-92.8). Four-dose VE was
      lower in pre-schoolers born after 1996 (75.4%) than in those born 1995-1996, ~1%
      and ~21% of whom had received >=1 dose of whole-cell pertussis vaccines,
      respectively. VE was higher in pre-schoolers and adolescents who received a
      booster (92.8%and 96.5%, respectively). However, overall booster VC was only 19%
      and 76% in these age groups, respectively. CONCLUSIONS: We observed high VE of
      routine pertussis vaccination, with evidence of waning over time and improved VE
      after booster vaccination. Increased uptake and monitoring of recommended
      pertussis boosters is urgently recommended to decrease high pertussis morbidity
      particularly in older children and adolescents.

PMID- 25621763
TI  - Sense and nonsense of treatment of comorbid diseases in terminally ill patients.

PMID- 25621764
TI  - Translation of 5' leaders is pervasive in genes resistant to eIF2 repression.
AB  - Eukaryotic cells rapidly reduce protein synthesis in response to various stress
      conditions. This can be achieved by the phosphorylation-mediated inactivation of
      a key translation initiation factor, eukaryotic initiation factor 2 (eIF2).
      However, the persistent translation of certain mRNAs is required for deployment
      of an adequate stress response. We carried out ribosome profiling of cultured
      human cells under conditions of severe stress induced with sodium arsenite.
      Although this led to a 5.4-fold general translational repression, the protein
      coding open reading frames (ORFs) of certain individual mRNAs exhibited
      resistance to the inhibition. Nearly all resistant transcripts possess at least
      one efficiently translated upstream open reading frame (uORF) that represses
      translation of the main coding ORF under normal conditions. Site-specific
      mutagenesis of two identified stress resistant mRNAs (PPP1R15B and IFRD1)
      demonstrated that a single uORF is sufficient for eIF2-mediated translation
      control in both cases. Phylogenetic analysis suggests that at least two
      regulatory uORFs (namely, in SLC35A4 and MIEF1) encode functional protein
      products. 

PMID- 25621765
TI  - Defective apical extrusion signaling contributes to aggressive tumor hallmarks.
AB  - When epithelia become too crowded, some cells are extruded that later die. To
      extrude, a cell produces the lipid, Sphingosine 1-Phosphate (S1P), which
      activates S1P2 receptors in neighboring cells that seamlessly squeeze the cell
      out of the epithelium. Here, we find that extrusion defects can contribute to
      carcinogenesis and tumor progression. Tumors or epithelia lacking S1P2 cannot
      extrude cells apically and instead form apoptotic-resistant masses, possess poor
      barrier function, and shift extrusion basally beneath the epithelium, providing a
      potential mechanism for cell invasion. Exogenous S1P2 expression is sufficient to
      rescue apical extrusion, cell death, and reduce orthotopic pancreatic tumors and
      their metastases. Focal Adhesion Kinase (FAK) inhibitor can bypass extrusion
      defects and could, therefore, target pancreatic, lung, and colon tumors that lack
      S1P2 without affecting wild-type tissue.

PMID- 25621767
TI  - Sitting Time and Quality of Life in Older Adults: A Population-Based Study.
AB  - BACKGROUND: Quality of life is influenced by several factors and one aspect that
      has been negatively associated with health is sedentary behavior. Thus, the
      purpose of this study was to investigate the association between sitting time and
      quality of life in older adults. METHODS: This was a cross-sectional study
      conducted with individuals >= 60 years old residing in 24 Brazilian
      municipalities. Total sitting time was evaluated according to self-report of
      sitting time on a regular weekday and usual weekend day. The quality of life was
      evaluated by the WHOQOL-BREF and WHOQOL-OLD instruments. RESULTS: 3206 older
      adults were analyzed. In the univariate logistic regression analysis, all domain
      and facets of quality of life were associated to the longest sitting time;
      however, in the multivariate analysis, only the physical domain and the social
      participation facet remained significant in the model. After adjustment for sex,
      age group, education and regular practice of physical activity, longest sitting
      time remained associated with the lowest score for the physical domain (OR =
      1.80; 95% CI: 1.39-2.34) and social participation facet (OR = 1.42; 95% CI: 1.10
      1.84). CONCLUSION: In this study, older adults who sat the most presented the
      worst scores in the physical domain and social participation facet of quality of
      life.

PMID- 25621766
TI  - Genes associated with ant social behavior show distinct transcriptional and
      evolutionary patterns.
AB  - Studies of the genetic basis and evolution of complex social behavior emphasize
      either conserved or novel genes. To begin to reconcile these perspectives, we
      studied how the evolutionary conservation of genes associated with social
      behavior depends on regulatory context, and whether genes associated with social
      behavior exist in distinct regulatory and evolutionary contexts. We identified
      modules of co-expressed genes associated with age-based division of labor between
      nurses and foragers in the ant Monomorium pharaonis, and we studied the
      relationship between molecular evolution, connectivity, and expression. Highly
      connected and expressed genes were more evolutionarily conserved, as expected.
      However, compared to the rest of the genome, forager-upregulated genes were much
      more highly connected and conserved, while nurse-upregulated genes were less
      connected and more evolutionarily labile. Our results indicate that the genetic
      architecture of social behavior includes both highly connected and conserved
      components as well as loosely connected and evolutionarily labile components. 

PMID- 25621769
TI  - Giant Hemosiderotic Dermatofibroma: The Largest Giant Dermatofibroma Reported to
      Date.
AB  - Dermatofibroma (DF) is a relatively common benign fibrohistiocytic soft tissue
      tumor. It has a slightly greater incidence amongst females and typically presents
      itself during the midadult life as a slowly growing, firm dermal nodule, usually
      smaller than 2 cm in diameter, on the lower extremities. Giant DF is a rare
      clinical variant of DF characterized by unusually large size (>5 cm), which
      mimics malignant soft tissue tumor clinically. Twenty-six cases of giant DF have
      been reported so far. One of these giant DFs was a giant hemosiderotic DF. We
      report herein a case of a 47-year-old woman who presented with the largest DF
      reported in the literature to date. It was hemosiderotic. 

PMID- 25621768
TI  - Symptoms of depressed mood, disturbed sleep, and sexual problems in midlife
      women: cross-sectional data from the Study of Women's Health Across the Nation.
AB  - BACKGROUND: Women report many nonvasomotor symptoms across the menopausal
      transition, including sleep disturbances, depressed mood, and sexual problems.
      The co-occurrence of these three symptoms may represent a specific menopausal
      symptom triad. We sought to evaluate the interrelatedness of disturbed sleep,
      depressed mood, and sexual problems in the Study of Women's Health Across the
      Nation (SWAN) and determine the characteristics of women exhibiting this symptom
      triad. METHODS: SWAN is a multisite, multiethnic observational cohort study of
      the menopausal transition in the United States. Sleep disturbance, sexual
      problems, and depressed mood were determined based on self-report. Women who
      reported all three symptoms simultaneously were compared to those who did not.
      Logistic regression models estimated the association of demographic,
      psychosocial, and clinical characteristics with the symptom triad. RESULTS: Study
      participants (n=1716) were 49.8 years old on average and primarily in very good
      or excellent health. Sixteen and a half percent had depressed mood, 36.6% had a
      sleep problem, and 42.2% had any sexual problem. Five percent of women (n=90)
      experienced all three symptoms. Women with the symptom triad compared with those
      without had lower household incomes, less education, were surgically
      postmenopausal or late perimenopausal, rated their general health as fair or
      poor, and had more stressful life events and lower social support. CONCLUSIONS:
      The symptom triad of sleep disturbance, depressed mood, and sexual problems
      occurred in only 5% of women, and occurred most often among women with lower
      socioeconomic status, greater psychosocial distress, and who were surgically
      menopausal or in the late perimenopause.

PMID- 25621770
TI  - Antibiotic prophylaxis during the second and third trimester to reduce adverse
      pregnancy outcomes and morbidity.
AB  - BACKGROUND: Several studies have suggested that prophylactic antibiotics given
      during pregnancy improved maternal and perinatal outcomes, while others have
      shown no benefit and some have reported adverse effects. OBJECTIVES: To determine
      the effect of prophylactic antibiotics on maternal and perinatal outcomes during
      the second and third trimester of pregnancy for all women or women at risk of
      preterm delivery. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 July 2014) and reference lists of
      retrieved articles. SELECTION CRITERIA: Randomised controlled trials comparing
      prophylactic antibiotic treatment with placebo or no treatment for women in the
      second or third trimester of pregnancy before labour. DATA COLLECTION AND
      ANALYSIS: We assessed trial quality and extracted data. MAIN RESULTS: The review
      included seven randomised controlled trials. Approximately 2100 women were
      recruited to detect the effect of prophylactic antibiotic administration on
      pregnancy outcomes. Primary outcomesAntibiotic prophylaxis did not reduce the
      risk of preterm prelabour rupture of membranes (risk ratio (RR) 0.31; 95%
      confidence interval (CI) 0.06 to 1.49 (one trial, 229 women) low quality
      evidence) or preterm delivery (RR 0.85; 95% CI 0.64 to 1.14 (five trials, 1480
      women) low quality evidence). However, preterm delivery was reduced in the
      subgroup of pregnant women with a previous preterm birth who had bacterial
      vaginosis (BV) during the current pregnancy (RR 0.64; 95% CI 0.47 to 0.88 (one
      trial, 258 women), but there was no reduction in the subgroup of pregnant women
      with previous preterm birth without BV during the pregnancy (RR 1.08; 95% CI 0.66
      to 1.77 (two trials, 500 women)). A reduction in the risk of postpartum
      endometritis (RR 0.55; 95% CI 0.33 to 0.92 (one trial, 196 women)) was observed
      in high-risk pregnant women (women with a history of preterm birth, low
      birthweight, stillbirth or early perinatal death) and in all women (RR 0.53; 95%
      CI 0.35 to 0.82 (three trials, 627 women) moderate quality evidence). There was
      no difference in low birth weight (RR 0.86; 95% CI 0.53 to 1.39 (four trials; 978
      women) or neonatal sepsis (RR 11.31; 95% CI 0.64 to 200.79); and blood culture
      confirming sepsis was not reported in any of the studies. Secondary
      outcomesAntibiotic prophylaxis reduced the risk of prelabour rupture of membranes
      (RR 0.34; 95% CI 0.15 to 0.78 (one trial, 229 women) low quality evidence) and
      gonococcal infection (RR 0.35; 95% CI 0.13 to 0.94 (one trial, 204 women)). There
      were no differences observed in other secondary outcomes (congenital abnormality;
      small-for-gestational age; perinatal mortality), whilst many other secondary
      outcomes (e.g. intrapartum fever needing treatment with antibiotics) were not
      reported in included trials.Regarding the route of antibiotic administration,
      vaginal antibiotic prophylaxis during pregnancy did not prevent infectious
      pregnancy outcomes. The overall risk of bias was low except that incomplete
      outcome data produced high risk of bias in some studies. The quality of the
      evidence using GRADE was assessed as low for preterm prelabour rupture of
      membranes, low for preterm delivery, moderate for postpartum endometritis, low
      for prelabour rupture of membranes, and very low for chorioamnionitis.
      Intrapartum fever needing treatment with antibiotics was not reported in any of
      the included studies. AUTHORS' CONCLUSIONS: Antibiotic prophylaxis did not reduce
      the risk of preterm prelabour rupture of membranes or preterm delivery (apart
      from in the subgroup of women with a previous preterm birth who had bacterial
      vaginosis). Antibiotic prophylaxis given during the second or third trimester of
      pregnancy reduced the risk of postpartum endometritis, preterm rupture of
      membranes and gonococcal infection when given routinely to all pregnant women.
      Substantial bias possibly exists in the review's results because of a high rate
      of loss to follow-up and the small numbers of studies included in each of our
      analyses. There is also insufficient evidence on possible harmful effects on the
      baby. Therefore, we conclude that there is not enough evidence to recommend the
      use of routine antibiotics during pregnancy to prevent infectious adverse effects
      on pregnancy outcomes.

PMID- 25621773
TI  - [Sustainability and new anticancer drugs].
AB  - Economic problems have been reported ever more frequently to affect the chance of
      cancer treatment, and financial toxicity has become a relevant issue in many
      countries, including the United States. Data are lacking for Europe, but the
      impressive cost of all new anticancer drugs is challenging European countries
      like Italy, where public health systems are based on solidarity and equity of
      access. The increasing cost of the new drugs cannot be justified by their
      efficacy, because the size of their benefit is frequently marginal and may have
      little clinical impact. In Europe, new strategies in the management of regulatory
      matters are required that take into consideration economic issues as one of the
      main aspect to establish the value of the new anticancer drugs. 

PMID- 25621774
TI  - [Social media and health communication: do we need rules?].
AB  - Social media, online social networks and apps for smartphones and tablets are
      changing the way to communicate health and health issues to consumers and health
      professionals. Google, Facebook, Apple, and other companies have launched tools
      to make easier the doctor-patient communication, to group patients with similar
      diseases allowing them to share stories, experiences, and opinions, and to
      remotely track and monitor users health and wellbeing. However several concerns
      about patients' and consumers' privacy remain. Doctor-patient communication
      through e-mail and social media also introduces other ethical and privacy issues
      that were addressed only by few medical societies with appropriate guidelines and
      policies. In addition, pharmaceutical companies have started to use social media
      channels to communicate with doctors, patients and consumers. This type of
      communication has been only partially regulated by the Food and Drug
      Administration with the recently published guidelines for industries. Similar
      concerns exist for health and medical applications for smartphones and tablets
      for which only few agencies (including Food and Drug Administration) are
      requiring a formal (even if restricted in typology) validation. It's time for
      Europe and Italy to adopt appropriate guidelines for the use of the new media in
      health communication. 

PMID- 25621771
TI  - FLZ attenuates learning and memory deficits via suppressing neuroinflammation
      induced by LPS in mice.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder in which
      neuroinflammation plays an important role. FLZ is a novel synthetic derivative of
      natural squamosamide. Previous studies demonstrated that FLZ had neuroprotective
      effects on AD models and showed strong anti-inflammatory property in Parkinson's
      disease models. However, whether the neuroprotective effects of FLZ on AD are
      associated with its anti-inflammatory property is still not fully elucidated. In
      this study, we aimed to investigate the ability of FLZ in modulating
      inflammation. The results showed that FLZ significantly improved memory deficits
      and alleviated neuronal damage as well as neuronal loss in the hippocampus of
      mice intracerebroventricular injected with lipopolysaccharide (LPS). Mechanistic
      studies revealed that the neuroprotective effects of FLZ were due to the
      suppression of neuroinflammation induced by LPS, as indicated by inactivation of
      astrocytes and microglia, reduced production of tumor necrosis factor-alpha,
      interleukin-1beta, and nitric oxide, as well as decreased expression of
      cyclooxygenase-2 and inducible nitric oxide synthase. The beneficial effects of
      FLZ on AD were further supported by the finding that FLZ attenuated beta-amyloid
      production through inhibiting beta-amyloid precursor protein cleaving enzyme 1
      expression. These results suggested that anti-inflammatory agent could be useful
      for the treatment of AD. 

PMID- 25621775
TI  - [The importance of mutational status in prognosis and therapy of GIST].
AB  - GIST (gastrointestinal stromal tumor) are the most common mesenchymal tumors in
      gastrointestinal tract and are thought to derive from the cells of Cajal or their
      precursors that have a constitutional mutation in KIT and PDGFRA genes. There are
      KIT and PDGFRA genes mutations detected before the start of therapy that are
      believed to be related to GIST pathogenesis and some secondary mutations causing
      drug resistance and progression of disease. The most common KIT mutations are
      detected in exon 11 (66-71%), exon 9 (10-13%), exon 13,14,17 (1% each). PDGFRA
      mutations (8%) are described in exon 18 (5-6%), 12 (1%) and 14 (1%). No mutations
      are detected in 5-10% of tumors and those subtypes are called wild type GIST
      (WT). Imatinib mesilate is a selective inhibitor of KIT and PDGFRA with an
      antityrosine kinase activity (TKI) used in advanced or metastatic GIST as well as
      in adjuvant setting after complete resection of neoplasm. Imatinib has radically
      changed the therapy and prognosis of GIST, but sensitivity of the disease is
      different on the basis of leading mutations. GIST KIT exon 11 mutated manifests
      response rate in 80% of cases, exon 9 in 40% and GIST WT in 14%. PDGFRA shows a
      mild sensitivity to drug (66%) except the exon 18 D842 V mutation which is
      totally resistant. Unfortunately up to 15% of GIST have a primary resistance to
      imatinib that means progression of the disease within 6-12 months after the start
      of therapy. Another 40-50% of GIST develops a secondary resistance after >24
      months of TKI treatment. Biopsy of progressing GIST shows multiple clonal origins
      with distinct mutational changes. Secondary resistance occurs almost exclusively
      in KIT mutated GIST with the appearances of T670I gatekeeper secondary mutation
      and less common in 14, 17, 18 exons. After progression of disease second line
      therapy is represented by sunitinib malate that overcomes the most common
      resistant mutations excepted PGDFRA D842V. Again, after few months of treatment,
      new different mutations appear and the disease progresses. Regorafenib is the
      third line therapy but too few data relates mutational status and regorafenib
      activity. In adjuvant setting only imatinib has a role. Two important studies
      (the USA ACOSOG Z 9001 and the German-Scandinavian study) fail to demonstrate
      that a specific mutation can predict a better DFS and OS in treated patients. On
      the contrary, volume of the tumor, number of mitosis and site of GIST are strong
      prognostic and predictive factors. In conclusion mutational analysis in GIST is
      at present more useful in metastatic setting than in adjuvant therapy. The
      insurgence of primary and secondary mutations during therapy is a fundamental
      step for disease progression. 

PMID- 25621776
TI  - [Cancer treatment in elderly patients: evidence and clinical research].
AB  - In 2020 the percentage of patients with a diagnosis of cancer in people with more
      than 65 years will exceed 70% and 28% in ethnic minorities. The treatment of
      cancer in these populations is challenging for the oncologists due to socio
      economic issues such as poverty, reduced access to the hospital care, level of
      education. The clinical pathway "diagnosis-treatment-cure", typical of the care
      of young patients has to be integrated in elderly patients with a more
      individualized treatment by means of comprehensive geriatric assessment (CGA).
      IADL (Instrumental Activities of Daily Living) have the best predictive role in
      oncological setting and their impairment significantly correlate with overall
      survival, chemotherapy toxicities and thirty days postoperative morbidities. The
      CGA is universally accepted as the most appropriate instrument to analitically
      evaluate the age related problems of elderly patients. The role of CGA is crucial
      to identify geriatric issues not easily diagnosed, to predict treatment
      toxicities, functional or cognitive decline, post operative complications and to
      estimate life expectancy. The CGA items are predictive of severe toxicity,
      however it is not clearly established which are the best performers and the best
      cut-offs points. Today CGA is integrated with physical performance tests (the
      most widely used is the "time up and go" test) and laboratory assay of
      Interleukin 6 and D-Dimer that correlate with mortality and physical decline.
      There are few prospective studies that evaluated the role of CGA in treatment
      choice. The first is a phase II study in solid tumors, the second is a
      haematological trial on non Hodgkin lymphoma. The largest trial is a 571 patients
      observational series that confirmed the role of CGA in decision making. The
      administration of CGA is time consuming and consequently some screening tools
      were developed. VES-13 is a 13 items tool that explores prevalently the
      functional status and the self reported health status. VES-13 showed a good
      sensibility (87.3%) but a low specificity (62%) with respect to CGA for the
      diagnosis of patients with disabilities. Overcash et al. proposed an abbreviated
      form of CGA using a reduced number of items of ADL, IADL, MMSE and GDS. There was
      a good correlation between complete and reduced scales (coefficient of
      correlation 0.8). G8 is a screening tool composed of 8 questions that explore
      functional, cognitive and nutritional status. The score with the best equilibrium
      between sensibility and specificity was 14 (sensibility 85% and specificity 65%).
      In the first observational trial age, hystotype, chemotherapy dose, haemoglobin
      (man: 11 g/dL; women: 10 g/dL), creatinine clearance less than 34 mL/min
      (Jelliffe formula), earing problems, at least a fall in the last six months,
      walking problems, low social activity, were related to a major risk of toxicity;
      in another trial IADL, diastolic blood pressure, LDH and MAX2 index were
      predictive of haematological toxicity, while performance status, Mini-Mental
      Status score, Mini-Nutritional Assessment (MNA) score and MAX2 index were
      predictive of non haematological toxicity. Based on these parameters a 0-2 score
      was developed. A recent "position article" of EORTC (European organization for
      Research and Treatment of Cancer) and SIOG analyzed the pro and the contra of the
      use of some indicators in elderly patients. The overall survival (OS) frequently
      used in classical clinical trial could give wrong messages as there are some
      competitive risks of death in elderly patients. Another important indicator is
      the disease specific survival (DSS). Concerning the design of clinical trials, a
      possible strategy is to enrol elderly patients without upper age limit and to
      plan stratification. An interesting trial design is the so called "extended
      trial" that allow to re-open the arm of a trial in which a too low number of
      older patients was enrolled. 

PMID- 25621777
TI  - [Cancer-related fatigue].
AB  - Cancer-related fatigue (CRF) is a very common and distressing symptom experienced
      by most cancer patients, during and after treatments and also at the end of life.
      There is no accepted definition of CRF, because it is a multifaceted symptom that
      involves multiple biopsychosocial aspects. Several scales for assessing CRF have
      been used, unidimensional or multidimensional, but there is no agreement
      regarding the best instrument to measure CRF. Concerning the CRF treatment,
      pharmacologic and non-pharmacologic interventions have been used. Pharmacologic
      therapies have been evaluated in few randomized clinical trials: corticosteroids
      demonstrated a superior efficacy to the placebo in terminal cancer patients;
      psychostimulants (methylfenidate, dexamphetamine, modafinil), antidepressant
      (paroxetine), acetilcholinesterase inhibitors (donepezil), l-carnitine and
      coenzyme Q(10) generally have reported negative results. Non-pharmacologic
      interventions (physical exercise, psychosocial interventions and other
      integrative interventions, such as yoga, ginseng, acupuncture) have been
      evaluated in several randomized and non-randomized studies, but with many
      methodological limitations. Therefore, the most effective non-pharmacological
      intervention remains unclear and the effect sizes are small. Further research is
      needed to delineate the optimal definition, measurement and treatment of CRF.

PMID- 25621778
TI  - [Epigenetics: a novel tool for early diagnosis and tumor therapy].
AB  - Epigenetics, first described by Conrad Waddington, defines how pathways setting a
      specific phenotype and heritable cellular functions are activated in a DNA
      independent way. Epigenetics concerns the study of genome structure and
      accessibility that regulates patterns of gene expression through the dynamic
      compaction and opening the chromatin structure. Vincent Allfrey profetically
      declared in 1964 that histone modifications could influence gene expression. In
      cancer very often cells show a profound modification of DNA methylation and
      mutations in chromatin regulators. These evidences provided therefore a clear
      link between epigenetics and neoplasia. Advanced molecular technology such as
      Deep-sequencing and ChIP-Seq revealed the frequent relocalization in cancer of
      many PTM readers such the Ac-Lys binding bromodomain. These results were
      important for the development of novel classes of epigenetic drugs some of which
      are inhibitors of histone modifyers or molecule interacting with reader domains.
      Since cancer imply profound changes in the epigenetic profile and in gene
      transcription a future challenge of molecular and chemical biology will be to
      develop novel epigenetic compounds able to correct the epigenetic disfunction
      and, possibly, coadiuvate canonical therapy in the cure of cancer. 

PMID- 25621779
TI  - [Treatment of metastatic castration-resistant prostate cancer].
AB  - The treatment of metastatic castration-resistant prostate cancer (mCRPC)
      represents one of the oncological fields where the most impressive improvements
      has been observed in the last decades. At the beginning of this century, the
      expected survival of mCRPC patients was not more than 12 months. After the
      introduction of docetaxel in the clinical practice in 2004, and the recent
      availability of new drugs cabazitaxel, abiraterone acetate, enzalutamide, and
      radium-223 the landscape is dramatically changed with an expected median survival
      of about three years. The possibility of administering docetaxel, abiraterone
      acetate, and enzalutamide as first line treatment, and cabazitaxel, abiretone
      acetate, and enzalutamide as second line, as well as the availability of radium
      223 for the treatment of mCRPC patients regardless of chemotherapy
      administration, changed the natural history of the disease. At the same time, it
      is probable that also the biology of the disease is changing with the appearance
      of mechanisms of resistance which are common to all the drugs. This plays a
      central role in sequencing the available drugs not only in the first and second
      line setting but also beyond the second line. The future challenges for the
      oncologists will be to develop new drugs able to overcome the resistances, mainly
      when they are native, to find the optimal sequence to optimize the use of
      available drugs, to place at the best place other active drugs, such as vaccines
      and radiopharmaceuticals, to exploit the new drugs also in a hormone-sensitive
      phase. 

PMID- 25621780
TI  - [Using Twitter in oncology. Research, continuing education, and advocacy].
AB  - Traditional mass media coverage has been enhanced by Twitter, an interactive,
      real-time media, useful in health care, and particularly in oncology. Social
      media such as Twitter are gaining increasing acceptance as tools for
      instantaneous scientific dialogue. Professional medical societies such as ASCO
      and ESMO are using microblogging to expand the reach of scientific communications
      at and around their scientific meetings. To widen the message and maximize the
      potential for word-of-mouth marketing using Twitter, organizations (such as AIOM,
      ASCO or ESMO) and industries need a strategic communications plan to ensure on
      going social media conversations. Twitter is a very powerful tool indeed that
      amplifies the results of scientific meetings, and conference organisers should
      put in place strategies to capitalise on this. This review demonstrates that
      cancer patients also share information more and more via Twitter about their
      disease, including diagnosis, symptoms, and treatments. This information could
      prove useful to health care providers. 

PMID- 25621781
TI  - [Facebook in oncology. Review of the literature].
AB  - Internet and particularly the so-called Web 2.0 are powerful tools of
      communication characterized by high user participation in the creation of content
      through various sites, such as those of social networking, where Facebook is the
      best known and most widely used. The aim of the present paper is to review the
      literature on the use of Facebook in health care. The international scientific
      literature of the past 10 years has been collected by major databases online.
      From the research were identified 262 articles of which 57 are considered
      relevant. The articles are schematically divided into three categories according
      to the topic: use of Facebook for psychosocial support for communication, for
      doctor-patient relationship, for institutional communication. The authors have
      identified the critical aspects and the possibility of using this tool in the
      communication and relationship between patients and health professionals. Despite
      the presence of critical issues, the use of social media is to be considered with
      interest and is worthy of study and research in the clinical setting. It should
      at the same time that health professionals are aware of the risks associated with
      the use of social networking but also trained in the use of the potential of
      these virtual tools that cannot replace real interactions but can support them. 

PMID- 25621782
TI  - [Gastrointestinal stromal tumors: a rare nosological entity and a model example
      for the use of personalized therapy with a molecular basis].
AB  - GIST (gastrointestinal stromal tumor) are stromal tumors of the gastrointestinal
      tract, belonging to a category of rare tumor called soft tissue sarcoma deriving
      from the Cajal mesenchymal cells. GIST present a peculiar immunohistochemical
      profile that is indispensable for a diagnostic confirmation: approximately 80% of
      cases present a mutation of the c-kit gene which codifies for a trans membrane
      receptor (antigen CD117) at tirosin-kinasic activity whose activation triggers
      cell proliferation. About 7% of GIST cases present mutations in the tirosin
      kinasic receptor homologous to c-kit, the PDGFRalpha. Recent studies show that a
      considerable variety exists in the molecular and genetic characteristics that
      guide the GIST pathogenesis, therefore allowing the identification of different
      molecular subtypes of GIST with different prognosis and sensitivities to the
      specific treatments. The presence of different subtypes in an illness that has
      been so recently discovered is a model for oncology. With the availability of
      very active and specific therapeutic agents against molecular alterations which
      cause the majority of cases of GIST, these tumors have become the models for
      personalized cancer treatments. 

PMID- 25621783
TI  - [Medicine and the movies].

PMID- 25621784
TI  - Detection, identification, and quantification of hydroxylated bis(2-ethylhexyl)
      tetrabromophthalate isomers in house dust.
AB  - Ultra-High Resolution LC/mass spectrometry (LC-UHRMS; Thermo Fisher Q-Exactive)
      was used to identify two novel isomers of hydroxylated bis(2-ethylhexyl)
      tetrabromophthalate (OH-TBPH) which were unexpectedly observed in a commercial
      standard of TBPH. By combining ultra-high resolution (UHR) mass spectra (MS(1)),
      mass errors to theoretical [TBPH-Br+O](-) were 2.1 and 1.0 ppm for the two
      isomers, UHR-MS(2) spectra and NMR analysis; the structures of the two compounds
      were identified as hydroxylated TBPH with a hydroxyl group on the aromatic ring.
      Relatively great proportions of the two isomers of OH-TBPH were detected in two
      technical products, Firemaster 550 (FM-550; 0.1% and 6.2%, respectively) and
      Firemaster BZ 54 (BZ-54; 0.1% and 7.9%), compared to a commercial standard (0.4%
      and 0.9%). To simultaneously analyze OH-TBPH isomers and TBPH in samples of dust,
      a method based on LC-UHRMS was developed to quantify the two compounds, using
      negative and positive ion modes, respectively. The instrumental limit of
      detection for TBPH was 0.01 MUg/L, which was 200-300 times better than
      traditional methods (2.5 MUg/L) based on gas chromatography-mass spectrometry.
      The analytical method combined with a Florisil cleanup was successfully applied
      to analyze TBPH and OH-TBPH in 23 indoor dust samples from Saskatoon,
      Saskatchewan, Canada. Two OH-TBPH isomers, OH-TBPH1 and OH-TBPH2, were detected
      in 52% and 91% of dust samples, respectively. Concentrations of OH-TBPH2 (0.35 +/
      1.0 ng/g) were 10-fold greater than those of OH-TBPH1 (0.04 +/- 0.88 ng/g) in
      dust, which was similar to profiles in FM-550 and BZ-54. TBPH was also detected
      in 100% of dust samples with a mean concentration of 733 +/- 0.87 ng/g. A
      significant (p < 0.001) log-linear relationship was observed between TBPH and OH
      TBPH isomers, further supporting the hypothesis of a common source of emission.
      Relatively small proportions of OH-TBPH isomers were detected in dust (0.01% +/-
      0.67 OH-TBPH1 and 0.1% +/- 0.60 OH-TBPH2), which were significantly less than
      those in technical products (p < 0.001). This result indicated different
      environmental behaviors of OH-TBPH and TBPH. Detection of isomers of OH-TBPH is
      important, since compounds with phenolic groups have often shown relatively
      greater toxicities than nonhydroxylated analogues. Further study is warranted to
      clarify the environmental behaviors and potential toxicities of OH-TBPH isomers. 

PMID- 25621785
TI  - Steam-etched spherical carbon/sulfur composite with high sulfur capacity and long
      cycle life for Li/S battery application.
AB  - Spherical carbon material with large pore volume and specific area was designed
      for lithium/sulfur (Li/S) soft package battery cathode with sulfur loading over
      75%, exhibiting good capacity output (about 1300 mAh g(-1)-S) and excellent
      capacity retention (70% after 600 cycles) at 0.1 C. The spherical carbon is
      prepared via in situ steam etching method, which has the advantages of low cost
      and easy scale up. 

PMID- 25621786
TI  - Close to home.

PMID- 25621787
TI  - The neural bases of cognition and behavior.

PMID- 25621788
TI  - Role of the striatopallidal pathway in renewal and reacquisition of alcohol
      seeking.
AB  - The ventral pallidum (VP) is a key component of the neural circuitry mediating
      relapse to drug seeking, but the critical afferent pathways to VP recruited
      during relapse remain poorly understood. We studied the role of the nucleus
      accumbens core (AcbC) -> VP pathway in ABA renewal and reacquisition of alcohol
      seeking. Rats received application of adenoviral vectors encoding eYFP,
      ChR2(H134R), or eNpHr3.0 to AcbC and implantation of fiber optic cannulas into VP
      to permit photostimulation of AcbC terminals there. Rats were then trained to
      self-administer alcoholic beer in 1 context (A), extinguished in a second context
      (B), tested in the extinction (ABB) and training (ABA) contexts, and were then
      tested for reacquisition of alcoholic beer seeking. There was ABA renewal of
      alcohol seeking, but neither optogenetic excitation nor inhibition of the AcbC ->
      VP pathway affected this renewal. In contrast, optogenetic inhibition of the AcbC
      -> VP striatopallidal pathway reduced reacquisition of alcohol seeking-measured
      either by the number of active nosepokes emitted or by the number of alcohol
      rewards earned and consumed. Moreover, optogenetic excitation of the AcbC -> VP
      striatopallidal pathway increased magazine entries during reacquisition test.
      This finding shows the importance of the AcbC -> VP pathway in controlling
      relapse when the drug reinforcer is present on test and is consistent with a role
      for the AcbC -> VP pathway in regulating the hedonic or incentive motivational
      properties of drug reinforcers.

PMID- 25621789
TI  - "Acceleration of image analyst training with transcranial direct current
      stimulation": Correction to McKinley et al. (2013).
AB  - Reports an error in "Acceleration of image analyst training with transcranial
      direct current stimulation" by R. Andy McKinley, Lindsey McIntire, Nathaniel
      Bridges, Charles Goodyear, Nitin B. Bangera, and Michael P. Weisend (Behavioral
      Neuroscience, 2013[Dec], Vol 127[6], 936-946). Nitin B. Bangera was omitted as a
      coauthor. The online version of this article has been corrected. (The following
      abstract of the original article appeared in record 2013-43049-012.) Humans today
      are routinely and increasingly presented with vast quantities of data that
      challenge their capacity for efficient processing. To restore the balance between
      man and machine, it is worthwhile to explore new methods for enhancing or
      accelerating this capacity. This study was designed to investigate the efficacy
      of transcranial DC stimulation (tDCS) to reduce training time and increase
      proficiency in spatial recognition using a simulated synthetic aperture radar
      (SAR) task. Twenty-seven Air Force active duty members volunteered to participate
      in the study. Each participant was assigned to 1 of 3 stimulation groups and
      received two, 90-min training sessions on a target search and identification task
      using SAR imagery followed by a test. The tDCS anode was applied to site F10
      according to the 10-20 electroencephalographic electrode convention while the
      cathode was placed on the contralateral bicep. Group 1 received anodal tDCS at 2
      mA for 30 min in the first training session and sham tDCS in the second session.
      Group 2 received the stimulation conditions in the opposite order. Group 3 did
      not receive stimulation at all. Results showed that participants receiving
      training plus tDCS attained visual search accuracies ~25% higher than those
      provided with sham stimulation or no stimulation. However, a corresponding
      performance improvement was not found in the first training session for the
      change detection portion of the task. This indicates that experience with the
      imagery is important in the tDCS-elicited performance improvements in change
      detection. (PsycINFO Database Record (c) 2015 APA, all rights reserved). 

PMID- 25621790
TI  - Age differences in prenatal testosterone's protective effects on disordered
      eating symptoms: developmental windows of expression?
AB  - Prenatal testosterone exposure may be protective against disordered eating.
      However, prior studies have produced mixed results. Developmental differences in
      prenatal testosterone's protective effects on disordered eating may explain these
      discrepancies. Indeed, studies have differed in the age of participants assessed,
      with data supporting prenatal testosterone effects on disordered eating in early
      adolescent and young adult samples but not in late adolescence. The present
      studies are the first to investigate age differences in prenatal testosterone's
      protective effects on disordered eating. Two indirect markers of higher prenatal
      testosterone were examined: (a) lower finger-length ratios (Study 1: index
      [2D]/ring [4D] finger [2D:4D]) and (b) lower disordered eating in female s from
      opposite-sex twin pairs (who are thought to be exposed to higher prenatal
      testosterone from their male co-twin) relative to female controls (Study 2).
      Participants were twins from the Michigan State University Twin Registry (Study
      1: n = 409; Study 2: n = 1,538) in early adolescence, late adolescence, or young
      adulthood. Disordered eating was assessed with well-validated questionnaires.
      Finger-length ratios were measured from hand scans, using electronic computer
      calipers. Findings were consistent across both studies. Higher prenatal
      testosterone (lower 2D:4D; females from opposite-sex twin pairs vs. controls)
      predicted lower disordered eating in early adolescence and young adulthood only.
      Prenatal testosterone-disordered eating associations were not observed during
      late adolescence. Results point to the possibility of developmental windows of
      expression for prenatal testosterone's protective effects on disordered eating
      and suggest that prior discrepant results may reflect age differences across
      samples.

PMID- 25621791
TI  - Noradrenergic and cholinergic effects on speed and sensitivity measures of phasic
      alerting.
AB  - An intense but task-irrelevant auditory accessory stimulus that is presented
      almost simultaneously with a visual imperative stimulus can reduce reaction times
      (RTs) to that stimulus. The information-processing locus and neural underpinnings
      underlying this phasic alerting effect are still poorly understood. The authors
      investigated a possible noradrenergic or cholinergic basis of the accessory
      stimulus effect in a double-blind pharmacological study (N = 18), in which
      healthy participants received a single dose of clonidine (an alpha2-adrenergic
      agonist), scopolamine (a muscarinic antagonist), and placebo in separate test
      sessions. A backward-masking procedure was used to examine, for the first time,
      the effect of accessory stimuli on perceptual sensitivity. The authors found that
      accessory stimuli enhanced perceptual sensitivity and decreased RTs to target
      stimuli, consistent with a recent hypothesis that phasic alerting speeds up
      stimulus encoding. In contrast to the authors' expectations, clonidine increased
      the accessory stimulus effect, a finding that seems at odds with earlier
      proposals that phasic alerting effects are mediated by a phasic noradrenergic
      response. Furthermore, the accessory stimulus effect was modulated to a similar
      extent by clonidine and scopolamine, suggesting that the effect of clonidine was
      not specific to the noradrenergic system. The results instead suggest that
      clonidine and scopolamine decrease general alertness and that these drug-related
      reductions in alertness yield room for compensatory performance improvements by
      phasic alerting.

PMID- 25621793
TI  - Sensitization of fear learning to mild unconditional stimuli in male and female
      rats.
AB  - Stress-enhanced fear learning (SEFL) refers to the long-lasting nonassociative
      sensitization produced by intense stress (e.g., repeated and unpredictable
      footshock) that results in increased fear learning to a mild conditioning regimen
      (e.g., one shock). SEFL experiments suggest that one component of posttraumatic
      behavior is inappropriately strong fear conditioning occurring to relatively mild
      stressors. Past reports of SEFL have used the same intensity (1 mA) of footshock
      to cause both the sensitization and conditioning of new fear. SEFL would be a
      particularly problematic component of posttrauma behavior if intense stress
      results in substantial fear conditioning under conditions that would not normally
      support conditioning. Therefore, we determined if SEFL occurred when the
      conditioning shock was substantially milder than the SEFL-inducing shock. The
      results indicate that exposure to a sensitizing regimen of shock can convert a
      mild footshock that normally does not support measurable levels of fear
      conditioning into one that causes substantial learned fear. Moreover, as the
      intensity of single footshock increases, so does the capacity of the prior
      stressor to contribute to the sensitization of fear responses. Consistent with
      prior studies, males acquired and retained a greater level of fear conditioning
      than female rats, however the level of sensitization did not differ between
      sexes.

PMID- 25621792
TI  - Lack of neuronal nitric oxide synthase results in attention deficit hyperactivity
      disorder-like behaviors in mice.
AB  - Nitric oxide (NO) is an important molecule for the proper development and
      function of the central nervous system. In this study, we investigated the
      behavioral alterations in the neuronal NO synthase knockout mice (NOS1 KO) with a
      deficient NO production mechanism in the brain, characterizing it as a potential
      rodent model for attention deficit hyperactivity disorder (ADHD). NOS1 KO
      exhibited higher locomotor activity than their wildtype counterparts in a novel
      environment, as measured by open field (OF) test. In a 2-way active avoidance
      paradigm (TWAA), we found sex-dependent effects, where male KO displayed deficits
      in avoidance and escape behavior, sustained higher incidences of shuttle
      crossings, and higher incidences of intertrial interval crossings, suggesting
      learning, and/or performance impairments. On the other hand, female KO
      demonstrated few deficits in TWAA. Molsidomine (MSD), a NO donor, rescued TWAA
      deficits in male KO when acutely administered before training. In a passive
      avoidance paradigm, KO of both sexes displayed significantly shorter step-through
      latencies after training. Further, abnormal spontaneous motor activity rhythms
      were found in the KO during the dark phase of the day, indicating dysregulation
      of rhythmic activities. These data indicate that NOS1 KO mimics certain ADHD-like
      behaviors and could potentially serve as a novel rodent model for ADHD.

PMID- 25621794
TI  - Astrocytes in the medial preoptic area modulate ejaculation latency in an
      experience-dependent fashion.
AB  - While sexually experienced males copulate at a higher frequency than sexually
      inexperienced males, there is still a great deal of variability in their
      behavior. Within the medial preoptic area (mPOA) of the hypothalamus, glutamate
      modulates some of this variability. Glutamate levels, for example, increase
      during sexual activity, peaking with ejaculation and falling precipitously during
      the post-ejaculation interval. Whereas lower glutamate levels after ejaculation
      translates to longer post-ejaculatory intervals, administration of glutamate
      uptake inhibitors into the mPOA increases the number of ejaculations a male rat
      achieves over a mating bout, and reduces the latency to ejaculate once mating
      begins. Because astrocytes modulate the availability of neuronal glutamate, we
      hypothesized that differences in the number of GFAP-positive astrocytes in the
      mPOA may account for variability in sexual behavior. To this end, we examined
      whether the number of astrocytes in the mPOA related to ejaculation latency as
      well as to the duration of the post-ejaculatory interval (PEI) in sexually
      experienced and sexually inexperienced males. Results indicate that the number of
      astrocytes negatively correlated with latency to reach ejaculations in sexually
      inexperienced but not sexually experienced rats while the number of astrocytes
      and PEI were not related. Astrocyte numbers did not vary between inexperienced
      and experienced subjects indicating that astrocyte processes may differentially
      project to sex-relevant glutamatergic synapses or that glutamatergic innervation
      of the mPOA changes as a function of sexual experience.

PMID- 25621795
TI  - Are changes in HLA Ags responsible for leukemia relapse after HLA-matched
      allogeneic hematopoietic SCT?
AB  - Loss of heterozygosity (LOH) has been shown to be associated with leukemia
      relapse after haploidentical transplantation. Whether such changes are an
      important cause of relapse after HLA-matched transplantation remains unclear. We
      retrospectively HLA-typed leukemic blasts for 71 patients with
      AML/myelodysplastic syndrome obtained from stored samples, and the results were
      compared with those obtained at diagnosis and/or before the transplant. No LOH or
      any other changes in HLA Ag were found in any of the samples tested post
      transplant as compared with pretransplant specimens. One patient had LOH in HLA
      class I Ag (HLA-A,-B and -C); however, these changes were present in the
      pretransplant sample indicating that they occurred before the transplant. We
      concluded that, in contrast with haploidentical transplantation, HLA loss does
      not have a major role as a mechanism of relapse after allogeneic transplantation
      with a closely HLA-matched donor. 

PMID- 25621796
TI  - I.v. BU/fludarabine plus melphalan or TBI in unrelated cord blood transplantation
      for high-risk hematological diseases.

PMID- 25621797
TI  - High-dose melphalan with autologous stem cell support in refractory Hodgkin
      lymphoma patients as a bridge to second transplant.
AB  - Persistence of disease after salvage therapy among relapsed or refractory Hodgkin
      lymphoma (HL) patients predicts poor outcome. Here, we report on 41 HL patients
      with active disease after salvage therapy and who received high-dose melphalan
      (HD-PAM) and auto-SCT as a bridge to a second autologous or an allogeneic
      transplantation between 2002 and 2013 at our center. Disease response was based
      on 18-fluoro-deoxyglucose-positron emission tomography results in all patients.
      Overall response rate after HD-PAM was 78% and it did not differ among PR or
      stable/progressive disease patients (P=1.00). Response was associated with better
      OS: hazard ratio=0.32 (95% confidence interval: 0.13-0.77, P=0.01) irrespective
      of disease status before HD-PAM. Thirty-three patients (80%) were able to
      complete the planned treatment, intended as tandem autologous or auto-allo
      transplant. Hematological and extrahematological toxicity of HD-PAM was
      manageable, without any treatment-related death. In conclusion, HD-PAM is a
      valuable therapeutic option in relapsed/refractory HL patients with active
      disease after salvage therapy, with an impressive 78% overall response rate and
      80% rate of proceeding to further transplantation. The present data may be
      integrated with the growing literature on new drugs in the field of
      relapsed/refractory HL. 

PMID- 25621799
TI  - Cord blood collection and banking from a population with highly diverse
      geographic origins increase HLA diversity in the registry and do not lower the
      proportion of validated cord blood units: experience of the Marseille Cord Blood
      Bank.
AB  - Several Cord Blood (CB) Bank studies suggested that ethnicity impaired CB unit
      (CBU) qualification. The Bone Marrow Donors Worldwide registries present an over
      representation of unrelated donors (UD) from Northwestern European descent. This
      raises the question of equality of access to hematopoietic stem cells transplant,
      especially in the Mediterranean zone, which has taken in many waves of
      immigration. The aim of our study is to address whether, in the Marseille CB
      Bank, CBU qualification rate is impaired by geographic origin. The study compared
      biological characteristics of 106 CBU disqualified for total nucleated cell (TNC)
      count (dCBU) and 136 qualified CBU in relation to registry enrichment and
      haplotype origin. A high proportion (>80%) of both dCBU and CBU had at least one
      non-European haplotype and enrich CB and UD registries to a higher extent than
      those with two European haplotypes (P<0.001). No difference was observed between
      TNC count and volume according to geographic origin. Our study shows that diverse
      Mediterranean origins do not have an impact on the CBU qualification rate.
      Partnership with Mediterranean birth clinics with highly trained staff is a
      reasonable option to increase the HLA diversity of CB Bank inventories and to
      improve the representation of minorities. 

PMID- 25621798
TI  - Pre-transplant diabetes mellitus is a risk factor for non-relapse mortality,
      especially infection-related mortality, after allogeneic hematopoietic SCT.
AB  - Diabetes mellitus (DM) is a factor in the hematopoietic cell transplantation
      comorbidity index. However, the impact of pre-transplant DM on morbidity and
      cause-specific non-relapse mortality (NRM) remains unclear. We performed a
      retrospective study with registry data that included a total of 7626 patients who
      underwent their first allogeneic hematopoietic SCT (HSCT) between 2007 and 2010.
      The median age was 44 years (range 0-88). Compared with patients without pre
      transplant DM (non-DM group, n=7248), patients with pre-transplant DM (DM group,
      n=378) were older and were more likely to have high-risk disease, a reduced
      intensity conditioning regimen and GVHD prophylaxis using tacrolimus.
      Multivariate analyses showed that pre-transplant DM was associated with increased
      risks of NRM (hazard ratio (HR)1.46, 95% confidence interval (CI) 1.21-1.76,
      P<0.01) and infection-related NRM (HR 2.08, 95% CI 1.58-2.73, P<0.01). The
      presence of pre-transplant DM was associated with an increased risk of overall
      mortality in a multivariate analysis (HR 1.55, 95% CI 1.35-1.78, P<0.01). In
      conclusion, pre-transplant DM was a risk factor for NRM, particularly infection
      related mortality, after allogeneic HSCT. To improve the clinical outcome in
      patients with DM, the benefits of strict infection control and appropriate
      glycemic control should be explored in future trials. 

PMID- 25621800
TI  - Efficiency of allogeneic hematopoietic SCT from HLA fully-matched non-sibling
      relatives: a new prospect of exploiting extended family search.
AB  - The best donors for hematopoietic SCT (HSCT) are fully-matched siblings. In
      patients without fully-matched siblings, HLA registries or cord blood banks are
      alternative strategies with some restrictions. Owing to the high rate of
      consanguineous marriage in our country, between 2006 and 2013, extended family
      searches were undertaken in Hematology-Oncology Research Center and Stem Cell
      Transplantation (HORCSCT), Tehran, Iran, in 523 HSCT candidates with parental
      consanguinity and no available HLA identical sibling. Fully-matched other
      relative donors were found for 109 cases. We retrospectively studied the HSCT
      outcome in these patients. Median time to neutrophil engraftment was 13 days
      (range: 9-31days). In 83 patients, full chimerism and in 17 patients, mixed
      chimerism was achieved. Acute GvHD (aGvHD) grade II-IV appeared in 36 patients
      (33%). The frequency of aGvHD development in various familial subgroups was NS.
      Five patients expired before day+100. In the surviving 104 cases, chronic GvHD
      developed in 20 patients (19.2%). The distantly related subgroup had
      significantly a higher rate of cGvHD (P=0.04). The 2-year OS and disease-free
      survival (DFS) were 76.7+/-4.5% and 71.7+/-4.7%, respectively. No significant
      difference in OS (P=0.30) and DFS (P=0.80) was unraveled between various familial
      relationships. Our considerable rate of fully-matched non-sibling family members
      and the favorable outcome support the rationale for extended family search in
      regions where consanguineous marriage is widely practiced. 

PMID- 25621802
TI  - Major ABO incompatible BMT in children: determining what residual volume of donor
      red cells can safely be infused following red cell depletion.
AB  - Major ABO incompatible BM transplantation carries a risk of acute haemolysis. Red
      cell depletion reduces this risk but not all incompatible RBC (iRBCs) are removed
      and in children the residual volume can be significant relative to body weight.
      We sought to determine the volume of iRBCs that can be safely given to children.
      All patients receiving fresh BM from a donor with a major ABO blood group
      mismatch between January 2000 and July 2013 at the Hospital for Sick Children,
      Toronto, were included. Seventy-eight patients were identified. The median volume
      of iRBCs transfused was 1.6 mL/kg (range 0.1-10.6 mL/kg). Thirty-five patients
      had minor haemolytic events and five patients had clinically significant adverse
      events. Two patients, who received 3.66 and 3.9 mL iRBCs/kg, developed renal
      impairment and in one case hypoxia and hyperbilirubinaemia. One patient had mild
      hypotension that resolved with i.v. fluid. Two patients developed hypotension
      secondary to sepsis and unrelated to BM infusion. Although signs of haemolysis
      occur, with appropriate hydration and monitoring of renal function, clinically
      significant adverse events related to the infusion of ABO incompatible BM are
      rare, and, in this study, were only seen in patients receiving >3 mL/kg of iRBCs
      per kg. 

PMID- 25621803
TI  - Treatment of donor-specific antibody-mediated graft rejection by
      immunochemotherapy, third-party DLI, plasmapheresis and immunoadsorption.

PMID- 25621801
TI  - Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T
      cell leukemia-lymphoma: a comparative study of recurrent lesions after
      transplantation and chemotherapy by the Nagasaki Transplant Group.
AB  - Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide
      long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients;
      however, the incidence of relapse associated with ATL remains high. To determine
      the clinical features of these patients at relapse, we retrospectively analyzed
      tumor lesions in 30 or 49 patients who relapsed following allo-SCT or
      chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture
      between 1997 and 2011. A multivariate analysis revealed that the development of
      abnormal lymphocytes in the peripheral blood of patients at relapse was less
      frequent after allo-SCT than after CHT (P<0.001). Furthermore, relapse with a new
      lesion only in the absence of the primary lesion was more frequent in allo-SCT
      (P=0.014). Lesions were more frequently observed in the central nervous systems
      of patients who relapsed with new lesions only (P=0.005). Thus, the clinical
      manifestation of relapsed ATL was slightly complex, especially in post-transplant
      patients. Our results emphasized the need to develop adoptive modalities for
      early and accurate diagnoses of relapsed ATL. 

PMID- 25621804
TI  - Paediatric reduced intensity conditioning: analysis of centre strategies on
      regimens and definitions by the EBMT Paediatric Diseases and Complications and
      Quality of Life WP.
AB  - The aim of this analysis was to explore the diversity of reduced intensity
      conditioning (RIC) in paediatric allo-SCT in daily practice across Europe. Data
      from the European Group for Blood and Marrow Transplantation (EBMT) Promise
      database from 1994 to 2008 were supplemented by a survey of EBMT centres
      performing paediatric allo-SCT on the current policy asking for the underlying
      diseases and for the drug combinations. Records from 161 centres from 30
      countries were analysed and 139 various RIC regimens were reported. More centres
      applied RIC for malignant rather than for non-malignant diseases. In general,
      fludarabine (FLU)-based regimens predominated except for BU-based regimens in
      myeloid malignancies and haemoglobinopathies. Treosulfan (TREO) was mainly
      applied for unspecified malignant diseases and for haemophagocytic diseases. FLU
      based regimens revealed the greatest number of different combinations.
      Correlating the number of regimens with the number of treating centres revealed
      the lowest variety in FLU and the highest variety in TBI and TREO. FLU/melphalane
      and FLU/CY were the most frequent combinations. This extreme heterogeneity in RIC
      may influence both the efficacy and the safety of the procedures, which requires
      further investigation. Optimization and standardization of RIC is the final goal
      to provide a platform for future prospective studies. 

PMID- 25621805
TI  - Impact of CR before and after allogeneic and autologous transplantation in
      multiple myeloma: results from the EBMT NMAM2000 prospective trial.
AB  - Previous studies have shown that obtaining complete hematologic remission (CR) in
      multiple myeloma is an important predictor of PFS and OS. This applies both to
      autologous and allogeneic transplantation. However, the importance of CR obtained
      before vs after second transplant or following allogeneic vs autologous
      transplantation is not clear. We investigated the role of CR analyzing data from
      the EBMT-NMAM2000 interventional prospective study comparing tandem
      autologous/reduced intensity conditioning allogeneic transplantation
      (auto/RICallo) to autologous transplantation-single or double (auto/auto).
      Allocation to treatment was performed according to availability of a matched
      sibling donor. Cox regression and multi-state models were applied. The long-term
      probability of survival in CR was superior in auto/RICallo, both comparing groups
      according to treatment allocated at start (28.8 vs 11.4% at 60 months, P=0.0004)
      and according to actual administration of second transplant (25.6 vs 9.6% at 60
      months, P=0.008). CR achieved before the second transplant was predictive for PFS
      (hazard ratio (HR)=0.44, P= 0.003) and OS (HR 0.51, P=0.047) irrespective of the
      type of second transplant. CR achieved after auto/RICallo was more beneficial for
      PFS (HR=0.53, P=0.027) than CR after auto/auto (HR=0.81, P=0.390), indicating a
      better durability of CR obtained after an allotransplant procedure. 

PMID- 25621806
TI  - Physiochemical disparity of mismatched HLA class I alloantigens and risk of acute
      GVHD following HSCT.
AB  - We determined whether assessment of the immunogenicity of individual donor
      recipient HLA mismatches based on differences in their amino-acid sequence and
      physiochemical properties predicts clinical outcome following haematopoietic SCT
      (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched
      grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts
      (n=168). A computer algorithm was used to determine the physiochemical disparity
      (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of
      mismatched HLA class I specificities in the graft-versus-host direction. Patients
      transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence
      of ?grade II acute GVHD (aGVHD) compared with patients transplanted with low
      EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had
      similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched
      grafts. Mortality was higher following single HLA-mismatched HSCT but was not
      correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA
      incompatibility based on physiochemical HLA disparity may enable better selection
      of HLA-mismatched donors in HSCT. 

PMID- 25621807
TI  - Superior efficacy but higher cost of plerixafor and abbreviated-course G-CSF for
      mobilizing hematopoietic progenitor cells (HPC) in AL amyloidosis.

PMID- 25621809
TI  - Constituting a public umbilical cord blood bank in South Africa.

PMID- 25621808
TI  - Comparison of outcomes at two institutions of patients with ALL receiving ex vivo
      T-cell-depleted or unmodified allografts.
AB  - We compared outcomes of adult patients receiving T-cell-depleted (TCD)
      hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan
      Kettering Cancer Center (MSKCC, N=52), with those of patients receiving
      conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or
      CR2. Patients received myeloablative conditioning. Thirty-nine patients received
      anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades
      2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5%
      vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse
      mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and
      9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in
      relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3
      years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age
      >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio
      (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was
      NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or
      conventional HCT, but TCD effectively reduces the rate of GVHD. 

PMID- 25621810
TI  - Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single
      institution.
AB  - The role of allogeneic hematopoietic SCT (allo-HCT) in multiple myeloma (MM)
      remains controversial. A total of 58 patients received an allo-HCT (25 of them
      with myeloablative conditioning-allo-MAC-and 33 with reduced-intensity
      conditioning-allo-RIC) at our institution over a 28-year period. The CR rate for
      allo-MAC was 36%. The incidence of grade III-IV acute GVHD (aGVHD) and chronic
      GVHD (cGVHD) was 28% and 39%, respectively The TRM at any time was 60% and the
      main causes of death were aGVHD or infectious complications not directly related
      to GVHD. The estimated PFS and OS at 15 years were 8% and 15%, respectively. The
      CR rate with allo-RIC was 45%. The incidence of grade III-IV aGVHD and cGVHD were
      24% and 41%, respectively. The TRM at any time was 33% and was mainly related to
      aGVHD. The estimated PFS and OS at 5 years were 22% and 38%, respectively.
      Despite its high TRM, a proportion of patients with high-risk myeloma (early
      relapse and newly diagnosed ultrahigh risk) may obtain long-term disease control
      with allo-HCT. New approaches aimed at decreasing the incidence of aGVHD, and
      consequently to decrease the TRM, are needed. 

PMID- 25621811
TI  - Interactions of amino acid side-chain analogs within membrane environments.
AB  - The interactions among four amino acid analog pairs (Asn, Ser, Phe, and Val)
      within the membrane environment were investigated using umbrella sampling
      molecular dynamics simulations. The results confirm generally expected
      qualitative trends of preferential association of polar compounds inside the
      membrane vs preferential interaction of hydrophobic compounds outside the
      membrane. Furthermore, correlations between amino acid interactions, membrane
      insertion, and membrane deformations are discussed and a detailed analysis of
      pair interaction energies is presented. A comparison of the energetics obtained
      from explicit lipid simulations with those from implicit membrane models reveals
      significant deviations and an improved parametrization of the heterogeneous
      dielectric generalized Born implicit model is provided that partially corrects
      for deficiencies in the implicit membrane model when compared with the new
      reference data from this study. 

PMID- 25621813
TI  - Challenges for internal medicine as the American College of Physicians celebrates
      its 100th anniversary.

PMID- 25621812
TI  - Product review on the JE vaccine IXIARO.
AB  - Japanese encephalitis virus, as the most important vaccine-preventable cause of
      viral encephalitis in Asia, is estimated to cause over 68,000 clinical cases
      yearly. In endemic areas, most Japanese encephalitis infections occur in children
      younger than 10 y and clinical manifestation of this disease is critical, because
      there is no effective treatment available. As JEV infections are regarded as one
      of the most serious viral causes of encephalitis and mass immunization programmes
      are generally recommended for residents in endemic areas, a safe and effective
      JEV vaccine was needed to protect them as well as others at risk. Due to the
      safety concerns with the mouse brain derived vaccine, second generation vaccines
      against JE produced in cell culture like Vero cells were developed. IXIARO(r) is
      a purified, inactivated aluminum-adjuvanted JE vaccine, based on the SA14-14-2
      virus strain, and is available in North America, Europe, Canada, Switzerland,
      Singapore, Hong Kong and Israel as well as in Australia & New Zealand (as
      JESPECT(r)).The safety, tolerability and immunogenicity profile of IXIARO(r) is
      well established through a number of clinical studies comparing IXIARO(r) with
      placebo as well as mouse brain derived vaccine. Recent data show that the global
      incidence of JE remains substantial, especially young children in endemic areas
      are most susceptible. As vaccination is the most feasible, reliable and cost
      effective tool for JE control, IXIARO(r) with confirmed excellent safety profile
      is highly recommendable, in particular for vaccination of children at risk. The
      European Commission as well as the FDA approved the extension of indication of
      IXIARO(r) to the pediatric segment (2 months of age and older) based on these
      data. 

PMID- 25621814
TI  - Hydrogen peroxide modulates the proliferation/quiescence switch in the liver
      during embryonic development and posthepatectomy regeneration.
AB  - AIMS: The liver undergoes marked changes in the rate of proliferation during
      normal development and regeneration through the coordinated activity of numerous
      signaling pathways. Little is known, however, about the events that act upstream
      of these signaling pathways. Here, we explore the modulatory effects of hydrogen
      peroxide (H2O2) on these pathways in the context of liver development and
      regeneration. RESULTS: We show that H2O2 production during liver development and
      after partial hepatectomy is tightly regulated in time by specific H2O2-producing
      and scavenging proteins and dose dependently triggers two distinct pathways.
      Sustained elevated H2O2 levels are required for the activation of ERK signaling
      and trigger a shift from quiescence to proliferation. Contrastingly, sustained
      decreased H2O2 levels are required for the activation of p38 signaling and
      trigger a shift from proliferation to quiescence. Both events impact the cyclin D
      and Rb pathways and are involved in liver development and regeneration.
      Pharmacological lowering of H2O2 levels reduces the extent of fetal hepatocyte
      proliferation and delays the onset of liver regeneration. Chemical augmentation
      of H2O2 levels in adult hepatocytes triggers proliferation and delays the
      termination of liver regeneration. INNOVATION: Our results challenge the
      traditional view of H2O2 as a deleterious stressor in response to liver damage
      and identify a novel role of endogenous H2O2 in liver development and
      regeneration. CONCLUSIONS: Endogenous H2O2 production is tightly regulated during
      liver development and regeneration. H2O2 constitutes an important trigger for the
      proliferation and quiescence transition in hepatocytes via the concentration
      dependent activation of the ERK or p38 pathway.

PMID- 25621815
TI  - Somebody's Fetish: Self-Objectification and Body Satisfaction Among Consensual
      Sadomasochists.
AB  - Considering that sexuality scholars claim consensual sadomasochists experience
      sexual objectification differently from the general population (Califia, 1994 ;
      Connell, 2002 ; Nussbaum, 1995 ), this study explored self-objectification
      (Fredrickson & Roberts, 1997 ) and body satisfaction among 121 self-identified
      consensual sadomasochists, 67 of whom also self-identified as women. Participants
      responded to an online survey and reported their self-objectification, self
      surveillance, body shame, and body satisfaction measures, along with their body
      mass index (BMI) and identification as dominant, submissive, or switch. The data
      revealed that the study participants' differed greatly in their sexual
      objectification experiences according to their genders, sexual orientations, and
      sadomasochistic identities, suggesting that consensual sadomasochism offers
      participants an environment partially free of the negative consequences resulting
      from Western beauty ideals.

PMID- 25621816
TI  - Lewis acid template-catalyzed asymmetric diels-alder reaction.
AB  - An asymmetric Diels-Alder reaction of 2,4-dienols and methyl acrylate utilizing a
      chiral Zn(II)/Mg(II) bimetallic template with low catalyst loading was
      successfully achieved. The bimetallic Lewis acid template derived from (R)
      5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol catalyzed the Diels-Alder
      reaction in the presence of molecular sieves 4 A to afford various functionalized
      bicyclic gamma-lactones with high enantiomeric purities. 

PMID- 25621817
TI  - Simulation study of the permeability of a model lipid membrane at the fluid-solid
      phase transition.
AB  - When a range of lipid bilayers are melted to the disordered fluid phase from the
      (much less permeable) ordered gel phase, their permeability to a variety of
      permeants shows a peak at the transition temperature and drops off with
      increasing temperature, rather than just rising as melting proceeds. To explore
      this anomalous behavior, a simulated coarse-grained lipid membrane model that
      exhibits a phase transition upon expansion or compression was studied to
      determine how the permeation rate of a simple particle depends on the phase
      composition in the two-phase region and on particle size. The permeation rate and
      each phase's area fraction and area density could be directly calculated, along
      with the probability that the permeant would cross in either phase or in
      interfacial regions. For large permeants and system sizes, conditions could be
      found where permeability increases upon compression of the bilayer. Permeation
      was negligible in the gel phase and, in contrast to the predictions of the "leaky
      interface" hypothesis, was not enriched in interfacial regions. The anomalous
      effect could instead be attributed to an increase in the area per lipid of fluid
      phase domains. This result motivated a model for the decrease in effective
      permeability barrier through fluid-phase domains arising from a decrease in the
      length of the gel/fluid interface at the midpoint of a permeation event. 

PMID- 25621818
TI  - Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From
      Bench to Small and Large Animal Myocardial Ischemia Studies.
AB  - Cardiovascular disease is the leading cause of death globally, and stem cell
      therapy remains one of the most promising strategies for regeneration or repair
      of the damaged heart. We report that human placenta-derived multipotent cells
      (hPDMCs) can modulate cardiac injury in small and large animal models of
      myocardial ischemia (MI) and elucidate the mechanisms involved. We found that
      hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with
      mouse neonatal cardiomyocytes. Moreover, hPDMCs exert strong proangiogenic
      responses in vitro toward human endothelial cells mediated by secretion of
      hepatocyte growth factor, growth-regulated oncogene-alpha, and interleukin-8. To
      test the in vivo relevance of these results, small and large animal models of
      acute MI were induced in mice and minipigs, respectively, by permanent left
      anterior descending (LAD) artery ligation, followed by hPDMC or culture medium
      only implantation with follow-up for up to 8 weeks. Transplantation of hPDMCs
      into mouse heart post-acute MI induction improved left ventricular function, with
      significantly enhanced vascularity in the cell-treated group. Furthermore, in
      minipigs post-acute MI induction, hPDMC transplantation significantly improved
      myocardial contractility compared to the control group (p = 0.016) at 8 weeks
      postinjury. In addition, tissue analysis confirmed that hPDMC transplantation
      induced increased vascularity, cardiomyogenic differentiation, and antiapoptotic
      effects. Our findings offer evidence that hPDMCs can modulate cardiac injury in
      both small and large animal models, possibly through proangiogenesis,
      cardiomyogenesis, and suppression of cardiomyocyte apoptosis. Our study offers
      mechanistic insights and preclinical evidence on using hPDMCs as a therapeutic
      strategy to treat severe cardiovascular diseases.

PMID- 25621819
TI  - Explicit vs. implicit emotional processing: The interaction between processing
      type and executive control.
AB  - The current study examined whether the interaction between emotion and executive
      control (EC) is modulated by the processing type of the emotional information.
      Namely, whether the emotional information is explicitly processed, implicitly
      processed or passively viewed. In each trial, a negative or neutral picture
      preceded an arrow-flanker stimulus that was congruent or incongruent. Incongruent
      stimuli are known to recruit EC. Explicit processing of the pictures (Experiment
      1a), which required responding to their emotional content, resulted in emotional
      interference for congruent but not for incongruent stimuli. Similar effects were
      shown for the passive viewing condition (Experiment 2). In contrast, implicit
      processing (Experiment 1b), which required responding to non-emotional content,
      resulted in emotional interference for both congruent and incongruent stimuli.
      Thus, our findings indicate that implicit emotional processing affects
      performance independently of EC recruitment. In contrast, explicit emotional
      processing and passive viewing of emotional pictures lead to reduced emotional
      interference when EC is recruited. 

PMID- 25621820
TI  - Cerebellar areas dedicated to social cognition? A comparison of meta-analytic and
      connectivity results.
AB  - A recent meta-analysis explored the role of the cerebellum in social cognition
      and documented that this part of the brain is critically implicated in social
      cognition, especially in more abstract and complex forms of mentalizing. The
      authors found an overlap with clusters involved in sensorimotor (during mirror
      and self-judgment tasks) as well as in executive processes (across all tasks)
      documented in earlier nonsocial cerebellar meta-analyses, and hence interpreted
      their results in terms of a domain-general function of the cerebellum. However,
      these meta-analytic results might be interpreted in a different, complementary
      way. Indeed, the results reveal a striking overlap with the parcellation of
      cerebellar topography offered by a recent functional connectivity analysis. In
      particular, the majority of social cognitive activity in the cerebellum can also
      be explained as located within the boundaries of a default/mentalizing network of
      the cerebellum, with the exception of the involvement of primary and integrative
      somatomotor networks for self-related and mirror tasks, respectively. Given the
      substantial overlap, a novel interpretation of the meta-analytic findings is put
      forward suggesting that cerebellar activity during social judgments might reflect
      a more domain-specific mentalizing functionality in some areas of the cerebellum
      than assumed before. 

PMID- 25621821
TI  - Relationships among depressive, passive-aggressive, sadistic and self-defeating
      personality disorder features with suicidal ideation and reasons for living among
      older adults.
AB  - OBJECTIVES: Suicide among older adults is a major public health problem in the
      USA. In our recent study, we examined relationships between the 10 standard DSM-5
      personality disorders (PDs) and suicidal ideation, and found that the PD
      dimensions explained a majority (55%) of the variance in suicidal ideation. To
      extend this line of research, the purpose of the present follow-up study was to
      explore relationships between the four PDs that previously were included in prior
      versions of the DSM (depressive, passive-aggressive, sadistic, and self
      defeating) with suicidal ideation and reasons for living. METHOD: Community
      dwelling older adults (N = 109; age range = 60-95 years; 61% women; 88% European
      American) completed anonymously the Coolidge Axis II Inventory, the Reasons for
      Living Inventory (RFL), and the Geriatric Suicide Ideation Scale (GSIS). RESULTS:
      Correlational analyses revealed that simple relationships between PD scales with
      GSIS subscales were generally stronger than with RFL subscales. Regarding GSIS
      subscales, all four PD scales had medium-to-large positive relationships, with
      the exception of sadistic PD traits, which was unrelated to the death ideation
      subscale. Multiple regression analyses showed that the amount of explained
      variance for the GSIS (48%) was higher than for the RFL (11%), and this finding
      was attributable to the high predictive power of depressive PD. CONCLUSION: These
      findings suggest that depressive PD features are strongly related to increased
      suicidal thinking and lowered resilience to suicide among older adults.
      Assessment of depressive PD features should also be especially included in the
      assessment of later-life suicidal risk.

PMID- 25621822
TI  - Enantioselective direct Mannich reactions of cyclic beta-ketoesters catalyzed by
      chiral phosphine via a novel dual-reagent catalysis.
AB  - A combination of an amino acid derived chiral phosphine catalyst and methyl
      acrylate efficiently catalyzed the direct Mannich reaction of cyclic beta
      ketoesters and N-Boc-aldimines. The dual-reagent catalysis was presumed to
      function through the formation of a zwitterion, which catalyzed the reaction with
      excellent stereocontrol via a hydrogen-bonding assisted chiral ion-pair pathway. 

PMID- 25621823
TI  - Beneficial effects of a multifaceted 1-year lifestyle intervention on metabolic
      abnormalities in obese adolescents with and without sleep-disordered breathing.
AB  - Obesity is considered a chronic subinflammatory disease and is a risk factor for
      many diseases such as sleep-disordered breathing (SDB). Although the interaction
      between obesity and sleep has been explored, not much is known about SDB in the
      adolescent population. Thus, the aims of this study were, first, to verify the
      effect of 1 year of interdisciplinary therapy on inflammatory markers in SDB and
      without SDB and, second, to investigate the influence of SDB on the result of the
      therapy by comparing these groups. A total of 36 obese adolescents were enrolled;
      however, only 24 completed the therapy (SDB group, n=12; non-SDB obese group,
      n=12). Sleep, anthropometric, metabolic, and inflammatory profiles were evaluated
      at baseline and after the treatment. In both groups, the therapy was able to
      improve all anthropometric variables. Metabolic parameters such as insulin,
      homeostasis model assessment (HOMA), and quantitative insulin sensitivity check
      index (QUICKI) were significantly improved only in non-SDB group. In both groups,
      the inflammatory state was significantly improved by the reduction in the
      leptin/adiponectin ratio. After the intervention, both groups no longer presented
      the hyperleptinemic state, favoring not only the inflammatory state, but also
      neuroendocrine regulation. Regarding the sleep parameter, the SDB group improved
      significantly in all respiratory events, and after therapy only four patients
      remained with SDB. Furthermore, there was an increase in sleep time. The
      lifestyle intervention was able to improve anthropometric, metabolic, and
      inflammatory parameters in both groups; however, the presence of SDB impaired
      better results. The data supported that the inclusion of SDB in the metabolic
      syndrome because of the link shown between them. 

PMID- 25621824
TI  - Protein arginine deiminase 2 binds calcium in an ordered fashion: implications
      for inhibitor design.
AB  - Protein arginine deiminases (PADs) are calcium-dependent histone-modifying
      enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2
      functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the
      citrullination of histone tail arginine residues at ER binding sites. Although an
      attractive therapeutic target, the mechanisms that regulate PAD2 activity are
      largely unknown, especially the detailed role of how calcium facilitates enzyme
      activation. To gain insights into these regulatory processes, we determined the
      first structures of PAD2 (27 in total), and through calcium-titrations by X-ray
      crystallography, determined the order of binding and affinity for the six calcium
      ions that bind and activate this enzyme. These structures also identified several
      PAD2 regulatory elements, including a calcium switch that controls proper
      positioning of the catalytic cysteine residue, and a novel active site shielding
      mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium
      exchange studies support these structural findings. The identification of
      multiple intermediate calcium-bound structures along the PAD2 activation pathway
      provides critical insights that will aid the development of allosteric inhibitors
      targeting the PADs. 

PMID- 25621827
TI  - Students Explore Supportive Transportation Needs of Older Adults.
AB  - Students in an undergraduate applied research in aging class learned about
      qualitative research methods by analyzing previously collected narratives. The
      interviews were with 32 participants who were national experts in senior
      transportation in the United States. The purpose of the study was to explore the
      specialized supportive mobility needs of community-residing older adults. The
      policy goal of the study was to expand the discussion on levels of assistance
      needed in senior transportation. The educational goal of the study was to expose
      undergraduate students to qualitative research methods, having them analyze
      transcripts and audio recordings. In preparation for the research, students
      reviewed the current literature in transportation and aging and learned that the
      ability to get to where you want to go, when you want to go there, is a key
      factor for aging-in-place in our communities. When that ability is compromised,
      the informal network of family and friends may not be a sustainable
      transportation option. Students were divided into three analysis groups by the
      domains of challenges, strategies, and policies and coded themes and subthemes
      through an iterative process. An important subtheme that emerged was the
      connection of community mobility to health care outcomes.

PMID- 25621826
TI  - The long intergenic noncoding RNA landscape of human lymphocytes highlights the
      regulation of T cell differentiation by linc-MAF-4.
AB  - Long noncoding RNAs are emerging as important regulators of cellular functions,
      but little is known of their role in the human immune system. Here we
      investigated long intergenic noncoding RNAs (lincRNAs) in 13 subsets of T
      lymphocytes and B lymphocytes by next-generation sequencing-based RNA sequencing
      (RNA-seq analysis) and de novo transcriptome reconstruction. We identified over
      500 previously unknown lincRNAs and described lincRNA signatures. Expression of
      linc-MAF-4, a chromatin-associated lincRNA specific to the TH1 subset of helper T
      cells, was inversely correlated with expression of MAF, a TH2-associated
      transcription factor. Downregulation of linc-MAF-4 skewed T cell differentiation
      toward the TH2 phenotype. We identified a long-distance interaction between the
      genomic regions of the gene encoding linc-MAF-4 and MAF, where linc-MAF-4
      associated with the chromatin modifiers LSD1 and EZH2; this suggested that linc
      MAF-4 regulated MAF transcription through the recruitment of chromatin modifiers.
      Our results demonstrate a key role for lincRNA in T lymphocyte differentiation. 

PMID- 25621825
TI  - Transcriptional programs define molecular characteristics of innate lymphoid cell
      classes and subsets.
AB  - The recognized diversity of innate lymphoid cells (ILCs) is rapidly expanding.
      Three ILC classes have emerged, ILC1, ILC2 and ILC3, with ILC1 and ILC3 including
      several subsets. The classification of some subsets is unclear, and it remains
      controversial whether natural killer (NK) cells and ILC1 cells are distinct cell
      types. To address these issues, we analyzed gene expression in ILCs and NK cells
      from mouse small intestine, spleen and liver, as part of the Immunological Genome
      Project. The results showed unique gene-expression patterns for some ILCs and
      overlapping patterns for ILC1 cells and NK cells, whereas other ILC subsets
      remained indistinguishable. We identified a transcriptional program shared by
      small intestine ILCs and a core ILC signature. We revealed and discuss
      transcripts that suggest previously unknown functions and developmental paths for
      ILCs. 

PMID- 25621828
TI  - Effects of carbon nanotubes on atrazine biodegradation by Arthrobacter sp.
AB  - The environmental risks of engineered nanoparticles have attracted attention.
      However, little is known regarding the effects of carbon nanotubes (CNTs) on the
      biodegradation and persistence of organic contaminants in water. We investigated
      the impacts of pristine and oxidized multiwalled CNTs on the atrazine
      biodegradation rate and efficiency using Arthrobacter sp. At a concentration of
      25mg/L, the CNTs enhanced the biodegradation rate by up to 20%; however, at a
      concentration of 100mg/L, the CNTs decreased the biodegradation rate by up to
      50%. The stimulation effects resulted from enhanced bacterial growth and the
      overexpression of degradation genes. The inhibitory effects resulted from the
      toxicity of the CNTs at high concentrations. The differences between the two CNTs
      at tested concentrations were not significant. The biodegradation efficiency was
      not impacted by adsorption, and the pre-adsorbed atrazine on the CNTs was fully
      biodegraded when the CNT concentration was <=25mg/L. This finding was consistent
      with the lack of observable desorption hysteresis for atrazine on the tested
      CNTs. Our results indicate that CNTs can enhance or inhibit biodegradation
      through a balance of two effects: the toxic effects on microbial activity and the
      effects of the changing bioavailability that result from adsorption and
      desorption.

PMID- 25621829
TI  - To prevent the occurrence of black water agglomerate through delaying
      decomposition of cyanobacterial bloom biomass by sediment microbial fuel cell.
AB  - Settlement of cyanobacterial bloom biomass (CBB) into sediments in eutrophic
      lakes often induced the occurrence of black water agglomerate and then water
      quality deterioration. This study investigated the effect of sediment microbial
      fuel cell (SMFC) on CBB removal in sediments and related water pollution.
      Sediment bulking and subsequent black water from decomposition of settled CBB
      happened without SMFC, but were not observed over 100-day experiments with SMFC
      employment. While CBB in sediments improved power production from SMFC, the
      removal efficiency of organic matters in CBB-amended sediments with SMFC was
      significantly lower than that without SMFC. Pyrosequencing analysis showed higher
      abundances of the fermentative Clostridium and acetoclastic methanogen in CBB
      amended bulk sediments without SMFC than with SMFC at the end of experiments.
      Obviously, SMFC operation changed the microbial community in CBB-amended
      sediments, and delayed the CBB degradation against sediment bulking. Thus, SMFC
      could be potentially applied as pollution prevention in CBB-settled and sensitive
      zones in shallow lakes.

PMID- 25621830
TI  - Exchangeable cations-mediated photodegradation of polycyclic aromatic
      hydrocarbons (PAHs) on smectite surface under visible light.
AB  - Clay minerals saturated with different exchangeable cations are expected to play
      various roles in photodegradation of polycyclic aromatic hydrocarbons (PAHs) via
      direct and/or indirect pathways on clay surfaces. In the present study,
      anthracene and phenanthrene were selected as molecule probes to investigate the
      roles of exchangeable cations on their photodegradation under visible light
      irradiation. For five types of cation-modified smectite clays, the
      photodegradation rate of anthracene and phenanthrene follows the order:
      Fe(3+)>Al(3+)>Cu(2+)>>Ca(2+)>K(+)>Na(+), which is consistent with the binding
      energy of cation-pi interactions between PAHs and exchangeable cations. The
      result suggests that PAHs photolysis rate depends on cation-pi interactions on
      clay surfaces. Meanwhile, the deposition of anthracene at the Na(+)-smectite and
      K(+)-smectite surface favors solar light absorption, resulting in enhanced direct
      photodecomposition of PAHs. On the other hand, smectite clays saturated with
      Fe(3+), Al(3+), and Cu(2+) are highly photoreactive and can act as potential
      catalysts giving rise to oxidative radicals such as O2(-) , which initiate the
      transformation of PAHs. The present work provides valuable insights into
      understanding the transformation and fate of PAHs in the natural soil environment
      and sheds light on the development of technologies for contaminated land
      remediation.

PMID- 25621831
TI  - Heterogeneous photo-Fenton decolorization of Orange II over Al-pillared Fe
      smectite: response surface approach, degradation pathway, and toxicity
      evaluation.
AB  - A ferric smectite clay material was synthesized and further intercalated with
      Al2O3 pillars for the first time with the aim of evaluating its ability to be
      used as heterogeneous catalyst for the photo-Fenton decolorization of azo dye
      Orange II. UV irradiation was found to enhance the activity of the catalyst in
      the heterogeneous photo-Fenton process. Catalyst loading of 0.5g/L and hydrogen
      peroxide concentration of 13.5mM yielded a remarkable color removal, accompanied
      by excellent catalyst stability. The decolorization of Orange II followed the
      pseudo-first-order kinetics for initial dye concentrations from 20 to 160mg/L.
      The central composite design (CCD) based on the response surface methodology
      (RSM) was applied to evaluate the effects of several operating parameters, namely
      initial pH, catalyst loading and hydrogen peroxide concentration, on the
      decolorization efficiency. The RSM model was derived and the response surface
      plots were developed based on the results. Moreover, the main intermediate
      products were separated and identified using gas chromatography-mass spectrometry
      (GC-MS) and a possible degradation pathway was proposed accordingly. The acute
      toxicity experiments illustrated that the Daphniamagna immobilization rate
      continuously decreased during 150min reaction, indicating that the effluent was
      suitable for sequential biological treatment.

PMID- 25621832
TI  - Ag/ZnO heterostructures and their photocatalytic activity under visible light:
      effect of reducing medium.
AB  - Decoration of ZnO by Ag is a promising method to improve its photocatalytic
      activity and extend the photoreactivity to the visible light. In this paper,
      Ag/ZnO heterostructures have been synthesised by photoreduction in various
      reducing mediums. When the Ag/ZnO nanocomposite arrays were obtained in the air,
      only a small amount of Ag was reduced. Ag nanosheets and nanoparticles were
      formed in the water and attached on the top and side surfaces of ZnO nanorods,
      forming Ag/ZnO heterostructures with a nano(sheet-rod-particle) multi-level
      structure. In the mixture of water and ethanol, a large amount of Ag nanoclusters
      was produced and embedded in the ZnO nanorod arrays. The influence of reducing
      mediums on the microstructure, morphology, quantity and dispersion of Ag
      nanostructures was investigated; and the effect of Ag component on the optical
      properties and visible light driven photocatalytic behaviour of the Ag/ZnO
      heterostructures was discussed. 

PMID- 25621833
TI  - Integrated synthesis of zeolites 4A and Na-P1 using coal fly ash for application
      in the formulation of detergents and swine wastewater treatment.
AB  - Several researchers have reported zeolite synthesis using coal ash for a wide
      range of applications. However, little attention has been given to green
      processes, including moderate synthesis conditions, using waste as raw material
      and effluent reuse or reduction. In this study, Brazilian coal fly ashes were
      used for integrated synthesis of zeolites 4A and Na-P1 by two different routes
      and under moderate operating conditions (temperature and pressure). Both
      procedures produced zeolites with similar conversions (zeolite 4A at 82% purity
      and zeolite Na-P1 at 57-61%) and high CEC values (zeolites 4A: 4.5meqCa(2+)g(-1)
      and zeolites Na-P1: 2.6-2.8meqNH4(+)g(-1)). However, process 1 generated less
      effluent for the zeolite mass produced (7mLg(-1)), with low residual Si and Al
      levels and 74% of the Si available in the coal fly ash incorporated into the
      zeolite, while only 55% is used in process 2. For use as a builder in detergents,
      synthetic zeolite 4A exhibited conformity parameters equal to or greater than
      those of the commercial zeolite adopted as reference. Treatment of swine
      wastewater with zeolite Na-P1 resulted in a high removal capacity for total
      ammoniacal nitrogen (31mgg(-1)).

PMID- 25621834
TI  - Allochthonous bioaugmentation in ex situ treatment of crude oil-polluted
      sediments in the presence of an effective degrading indigenous microbiome.
AB  - Oil-polluted sediment bioremediation depends on both physicochemical and
      biological parameters, but the effect of the latter cannot be evaluated without
      the optimization of the former. We aimed in optimizing the physicochemical
      parameters related to biodegradation by applying an ex-situ landfarming set-up
      combined with biostimulation to oil-polluted sediment, in order to determine the
      added effect of bioaugmentation by four allochthonous oil-degrading bacterial
      consortia in relation to the degradation efficiency of the indigenous community.
      We monitored hydrocarbon degradation, sediment ecotoxicity and hydrolytic
      activity, bacterial population sizes and bacterial community dynamics,
      characterizing the dominant taxa through time and at each treatment. We observed
      no significant differences in total degradation, but increased ecotoxicity
      between the different treatments receiving both biostimulation and
      bioaugmentation and the biostimulated-only control. Moreover, the added
      allochthonous bacteria quickly perished and were rarely detected, their addition
      inducing minimal shifts in community structure although it altered the
      distribution of the residual hydrocarbons in two treatments. Therefore, we
      concluded that biodegradation was mostly performed by the autochthonous
      populations while bioaugmentation, in contrast to biostimulation, did not enhance
      the remediation process. Our results indicate that when environmental conditions
      are optimized, the indigenous microbiome at a polluted site will likely
      outperform any allochthonous consortium.

PMID- 25621835
TI  - Photo-induced surface encoding of gold nanoparticles.
AB  - Photoreactive gold nanoparticles (NP) can be encoded in a spatially resolved
      fashion using direct laser writing techniques into variable patterns. The surface
      of the gold nanoparticles is imparted with photoreactivity by tethering photo
      caged dienes ('photoenols'), which are able to undergo a rapid Diels-Alder
      cycloaddition with surface anchored enes. Subsequent to surface encoding, the
      particles feature residual caged dienes, which can be reactivated for secondary
      surface encoding. 

PMID- 25621836
TI  - Synthesis and characterization of water-soluble, heteronuclear
      ruthenium(III)/ferrocene complexes and their interactions with biomolecules.
AB  - The reaction of Na[RuCl4(SO(CH3)2)2], 1, with one equivalent of FcCONHCH2C6H4N
      (Fc=FeC10H9), L1, FcCOOCH2CH2C3H3N2, L2, FcCOOC6H4N, L3, afforded the dinuclear
      species, Na[FcCONHCH2C6H4N[RuCl4(SO(CH3)2)]], RuL1,
      Na[FcCOOCH2CH2C3H3N2[RuCl4(SO(CH3)2)]], RuL2, Na[FcCOOC6H4N(RuCl4(SO(CH3)2))],
      RuL3, respectively, yielding, in each case, a ferrocene moiety bridged to a
      ruthenium center. The complexes were characterized by NMR, IR, and XRD (X-ray
      diffraction). The sulfoxide ligands are bonded to the metal through the sulfur
      atom. The complexes were evaluated for their biological activity with pBluescript
      DNA plasmid, and the protein BSA (bovine serum albumin). These reactions were
      monitored by XAS (X-ray absorption spectroscopy), EXAFS (extended X-ray
      Absorption Fine Structure), NMR, UV/visible, emission spectroscopy, and gel
      electrophoresis. Donor atoms from the biomolecules substitute for the chloride
      ligands in the parent complexes. 

PMID- 25621837
TI  - Correction: stratified community responses to methane and sulfate supplies in mud
      volcano deposits: insights from an in vitro experiment.

PMID- 25621838
TI  - Challenges of improving the evidence base in smaller surgical specialties, as
      highlighted by a systematic review of gastroschisis management.
AB  - OBJECTIVE: To identify methods of improving the evidence base in smaller surgical
      specialties, using a systematic review of gastroschisis management as an example.
      BACKGROUND: Operative primary fascial closure (OPFC), and silo placement with
      staged reduction and delayed closure (SR) are the most commonly used methods of
      gastroschisis closure. Relative merits of each are unclear. METHODS: A systematic
      review and meta-analysis was performed comparing outcomes following OPFC and SR
      in infants with simple gastroschisis. Primary outcomes of interest were
      mortality, length of hospitalization and time to full enteral feeding. RESULTS:
      751 unique articles were identified. Eight met the inclusion criteria. None were
      randomized controlled trials. 488 infants underwent OPFC and 316 underwent SR.
      Multiple studies were excluded because they included heterogeneous populations
      and mixed intervention groups. Length of stay was significantly longer in the SR
      group (mean difference 8.97 days, 95% CI 2.14-15.80 days), as was number of post
      operative days to complete enteral feeding (mean difference 7.19 days, 95%CI 2.01
      12.36 days). Mortality was not statistically significantly different, although
      the odds of death were raised in the SR group (OR 1.96, 95%CI 0.71-5.35).
      CONCLUSIONS: Despite showing some benefit of OPFC over SR, our results are
      tempered by the low quality of the available studies, which were small and
      variably reported. Coordinating research through a National Paediatric Surgical
      Trials Unit could alleviate many of these problems. A similar national approach
      could be used in other smaller surgical specialties.

PMID- 25621839
TI  - MiR-203 suppresses ZNF217 upregulation in colorectal cancer and its oncogenicity.
AB  - Zinc finger protein 217 (ZNF217) is essential for cell proliferation and has been
      implicated in tumorigenesis. However, its expression and exact roles in
      colorectal cancer (CRC) remain unclear. In this study, we demonstrated that
      ZNF217 expression was aberrantly upregulated in CRC tissues and associated with
      poor overall survival of CRC patients. In addition, we found that ZNF217 was a
      putative target of microRNA (miR)-203 using bioinformatics analysis and confirmed
      that using luciferase reporter assay. Moreover, in vitro knockdown of ZNF217 or
      enforced expression of miR-203 attenuated CRC cell proliferation, invasion and
      migration. Furthermore, combined treatment of ZNF217 siRNA and miR-203 exhibited
      synergistic inhibitory effects. Taken together, our results provide new evidences
      that ZNF217 has an oncogenic role in CRC and is regulated by miR-203, and open up
      the possibility of ZNF217- and miR-203-targeted therapy for CRC. 

PMID- 25621840
TI  - Designing chimeric antigen receptors to effectively and safely target tumors.
AB  - The adoptive transfer of T cells engineered to express artificial chimeric
      antigen receptors CARs) that target a tumor cell surface molecule has emerged as
      an exciting new approach for cancer immunotherapy. Clinical trials in patients
      with advanced B cell malignancies treated with CD19-specific CAR-modified T cells
      (CAR-T) have shown impressive antitumor efficacy, leading to optimism that this
      approach will be useful for treating common solid tumors. Because CAR-T cells
      recognize tumor cells independent of their expression of human leukocyte antigen
      (HLA) molecules, tumors that escape conventional T cells by downregulating HLA
      and/or mutating components of the antigen processing machinery can be eliminated.
      The ability to introduce or delete additional genes in T cells has the potential
      to provide therapeutic cell products with novel attributes that overcome
      impediments to immune mediated tumor elimination in immunosuppressive tumor
      microenvironments. This review will discuss recent concepts in the development of
      effective and safe synthetic CARs for adoptive T cell therapy (ACT). 

PMID- 25621841
TI  - The evolution of checkpoint blockade as a cancer therapy: what's here, what's
      next?
AB  - Unleashing the immune system to fight cancer has become one of the main treatment
      modalities since the anti-CTLA-4 antibody, ipilimumab was approved for patients
      with advanced melanoma in 2011. Pembrolizumab and nivolumab, two anti-PD-1
      antibodies recently approved for the treatment of patients with metastatic
      melanoma, are being actively investigated for the treatment of multiple caners
      including lung, breast, bladder and renal cancers along with other anti-PD-1/L1
      antibodies. Early results of combining of anti-CTLA-4 antibody and anti-PD-1
      antibody treatment for advanced melanoma patients are showing impressive response
      rates with manageable toxicity profiles. There are several other checkpoint
      molecules that are likely potential inhibitory targets. The outcome of blocking
      some of these negative immune regulators, such as LAG-3 or TIM-3, is being
      pursued in the clinic or about to enter clinical development. Blockade of these
      molecules is demonstrating promising preclinical activity alone or when combined
      with anti-PD-1/L1. Future studies will define bio-markers of these therapies and
      how to target them alone or in combination with other immunotherapies,
      chemotherapy, radiotherapy and small molecule inhibitors. 

PMID- 25621843
TI  - Correction: HIV Cure Strategies: How Good Must They Be to Improve on Current
      Antiretroviral Therapy?

PMID- 25621844
TI  - A novel extraction method based on a reversible chemical conversion for the
      LC/MS/MS analysis of the stable organic germanium compound Ge-132.
AB  - Poly trans-[(2-carboxyethyl)germasesquioxane] (IUPAC name) is the most common
      water-soluble organic germanium compound. This compound is known as
      bis(carboxyethyl)germaniumsesquioxide and it is commonly called Ge-132; it is
      hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGPA) in water. We have
      developed a method for the quantification of THGPA in rat plasma, using a novel
      extraction method based on a reversible chemical conversion. THGPA in plasma is
      converted to 3-(trichlorogermyl)propanoic acid (TCGPA) under acidic conditions
      using concentrated hydrochloride, which is followed by extraction with
      chloroform. TCGPA is then converted back to THGPA through hydrolysis. The
      extraction recovery of this method is approximately 100%. Moreover, we
      synthesized deuterated Ge-132, which was used as an internal standard in our
      experiments. This method covers a linearity range of 0.01-5 MUg/mL for
      concentrations of THGPA in plasma. The intra-day and inter-day precisions of the
      analysis are about 4.1%, and the accuracy is within +/-2.6% at THGPA
      concentrations of 0.025, 0.25, and 2.5 MUg/mL. The total run time is 5 min. Our
      method was successfully applied to a pharmacokinetic investigation following oral
      administration of Ge-132. 

PMID- 25621842
TI  - Role of group 3 innate lymphoid cells in antibody production.
AB  - Innate lymphoid cells (ILCs) constitute a heterogeneous family of effector
      lymphocytes of the innate immune system that mediate lymphoid organogenesis,
      tissue repair, immunity and inflammation. The initial view that ILCs exert their
      protective functions solely during the innate phase of an immune response has
      been recently challenged by evidence indicating that ILCs shape adaptive immunity
      by establishing both contact-dependent and contact-independent interactions with
      multiple hematopoietic and non-hematopoietic cells, including B cells. Some of
      these interactions enhance antibody responses both systemically and at mucosal
      sites of entry. 

PMID- 25621845
TI  - Contrasting reactivities of silicon and germanium complexes supported by an N
      heterocyclic guanidine ligand.
AB  - We report the synthesis of an acyclic two-coordinate germylene supported by two
      bulky and electron donating N-heterocyclic guanidine [IPr?N](-) ligands (IPr =
      [(HCNDipp)2C:]; Dipp = [2,6-(i)Pr2C6H3]), and its reactivity with molecular
      hydrogen to form IPr?NH, which presumably proceeds via the unstable intermediate
      [H2Ge(N?IPr)2]. Our attempts to isolate the corresponding silylene [:Si(N?IPr)2]
      led to an unexpected ligand activation/rearrangement process involving N-C(aryl)
      bond cleavage within the N-heterocyclic guanidine ligand; this transformation was
      also studied by computational methods. 

PMID- 25621846
TI  - Building the interaction interfaces: host responses upon infection with
      microorganisms.
AB  - Research fields of plant symbiosis and plant immunity were relatively ignorant
      with each other until a little while ago. Recently, however, increasing
      intercommunications between those two fields have begun to provide novel aspects
      and knowledge for understanding relationships between plants and microorganisms.
      Here, we review recent reports on plant-microbe interactions, focusing on the
      infection processes, in order to elucidate plant cellular responses that are
      triggered by both symbionts and pathogens. Highlighting the core elements of host
      responses over biotic interactions will provide insights into general mechanisms
      of plant-microbe interactions. 

PMID- 25621847
TI  - Photo-induced living radical polymerization of acrylates utilizing a discrete
      copper(II)-formate complex.
AB  - A photo-polymerization protocol, utilizing a pre-formed and well-characterized
      Cu(II) formate complex, [Cu(Me6-Tren)(O2CH)](ClO4), mediated by UV light is
      described. In the absence of additional reducing agents and/or photosensitizers,
      ppm concentrations of the oxidatively stable [Cu(Me6-Tren)(O2CH)](ClO4), furnish
      near-quantitative conversions within 2 h, yielding poly(acrylates) with low
      dispersities (~1.10) and exceptional end-group fidelity, capable of undergoing in
      situ chain extension and block copolymerization.

PMID- 25621848
TI  - On crack growth in molar teeth from contact on the inclined occlusal surface.
AB  - Extracted human molar teeth are indented by hard balls laid at the central fossa,
      sectioned, and their interior examined for damage. Contact on the fissured enamel
      coat generally occurs on three distinct spots. The main forms of damage are
      radial cracks growing from the DEJ to the occlusal surface and median radial and
      cylindrical cracks growing from a contact spot to the DEJ. For large balls
      failure by edge chipping near a cusp apex may occur. The median cracks tend to
      run unstably to the DEJ upon reaching the middle part of the enamel coat. The
      corresponding load, PFM, and the load needed to initiate radial cracks at the
      DEJ, PFR, are taken to signal crown failure. The mean values of PFM and PFR are
      on the order of 1000N. A conical bilayer model defined by thickness d,
      inclination angle theta, failure stress sigmaF and toughness KC of the enamel
      coat is developed to assess crown failure. The analytical predictions for PFR and
      PFM agree well with the tests. The results indicate that enamel thickness is so
      designed as to ensure that PFR and PFM just exceed the maximum bite force under
      normal conditions while the choice of theta seems to reflect a compromise between
      needs to resist crown failure and break hard food particles. Both PFR and PFM are
      greatly reduced with reducing d, which points to the danger posed by tooth wear.
      The analytical expressions for PFR and PFM may also apply to other multi-cusp
      mammalian or prosthetic molar crowns. Cone cracking, suppressed in the
      anisotropic tooth enamel, may be an important failure mode in prosthetic crowns. 

PMID- 25621849
TI  - Effect of fiber addition on slow crack growth of a dental porcelain.
AB  - AIMS: To evaluate the effect of the processing method (conventional sintering, S,
      and heat-pressing, HP) and addition of potassium titanate fibers, PTF, on the
      microstructure, mechanical properties (flexural strength, sigmaf, and Weibull
      parameters, m and sigma5%), slow crack growth parameters n (stress corrosion
      susceptibility coefficient), and optical properties (translucency parameter, TP,
      and opalescence index, OI) of a feldsphatic dental porcelain. METHODS: Disks (n =
      240, O12 * 1 mm) of porcelain (Vintage-Halo, Shofu) were produced using S and HP
      methods with and without addition of 10 wt% (conventional sintering) or 5 wt%
      (heat-pressing) of PTF. For the S method, porcelain was sintered in a
      conventional furnace. In the HP technique, refractory molds were produced by lost
      wax technique. The porcelain slurry was dry-pressed (3t/30s) to form a cylinder
      with 12 mm (diameter) and 20mm (height), which was heat-pressed for 5 min/3.5 bar
      into the mold. Specimens were tested for biaxial flexural strength in artificial
      saliva at 37 degrees C. Weibull analysis was used to determine m and sigma5%.
      Slow crack growth (SCG) parameters were determined by the dynamic fatigue test,
      and specimens were tested in biaxial flexure at five stress rates: 10(-2), 10(
      1), 10(0), 10(1) and 10(2)MPa/s (n=10), immersed in artificial saliva at 37
      degrees C. Parameter n was calculated and statistically analyzed according to
      ASTM F394-78. Optical properties were determined in a spectrophotometer in the
      diffuse reflectance mode. RESULTS: The highest n value was obtained by the
      combination of heat-pressing with fiber addition (37.1) and this value was
      significantly higher than those obtained by both sintered groups (26.2 for
      control group and 27.7 for sintered with fiber). Although heat-pressing alone
      also resulted in higher n values compared to the sintered groups, there were no
      significant differences among them. Fiber addition had no effect on mechanical
      strength, but it resulted in decreased TP values and increased OI values for both
      processing methods. Heat-pressing alone was able to reduce the porosity level of
      the porcelain. CONCLUSIONS: Addition of PTF combined with heat-pressing can
      reduce strength degradation of a dental porcelain compared to sintered materials
      with or without fibers. Heat-pressing (HP) alone should be considered as a good
      alternative for clinical cases where high translucency is required.

PMID- 25621850
TI  - A mesoscale study of the degradation of bone structural properties in modeled
      microgravity conditions.
AB  - One of the most important alterations that occur in man and experimental animals
      during spaceflight concerns the skeletal system, and entails important bone loss
      and degradation of mechanical properties. In the present work we investigate ex
      vivo the long-term effects of weightlessness (simulated microgravity) on bone
      tissue, by comparing the mesoscale structural properties of weight-bearing rat
      tibial epiphyseal cancellous structures of healthy animals (ground controls) with
      those of identical bone explants maintained ex vivo in the Rotary Cell Culture
      System (RCCS) bioreactor, used to model, on ground, microgravity conditions. Bone
      structures were reconstructed by synchrotron radiation micro-CT, morphometric
      analyses were performed, and the apparent elastic properties were computed by
      means of a numerical model based on the Cell Method. Two novel results were
      achieved in this study. First of all, the skeletal modifications found in bone
      explants after 3-4 weeks of culture in the RCCS bioreactor are in perfect
      agreement with those observed in vivo after a long-term spaceflight (Mice Drawer
      System mission, 2009), thus confirming the relevance of our model in reproducing
      the effects of microgravity on whole bone tissue. Secondly, but not less
      importantly, our study points out that the degradation in bone structural
      performance (apparent mechanical properties) must be considered in order to
      achieve an accurate representation of trabecular bone modifications not only in
      osteoporotic bone diseases, but also in the microgravity-induced bone
      alterations. In conclusion, our findings, by proving that the association of the
      RCCS bioreactor-based culture method, used to model microgravity conditions, with
      numerical simulations able to quantify bone quality, represents the first ground
      based reliable model for investigating, ex vivo, some of the spaceflight effects
      on bone tissue, and open new perspectives to basic research and clinical
      applications. 

PMID- 25621851
TI  - Mechanical degradation of biological heart valve tissue induced by low diameter
      crimping: an early assessment.
AB  - Transcatheter aortic valve implantation (TAVI) has become today an increasingly
      attractive procedure to relieve patients from aortic valve disease. However, the
      procedure requires crimping biological tissue within a metallic stent for low
      diameter catheter insertion purpose. This step induces specific stress in the
      leaflets especially when the crimping diameter is small. One concern about
      crimping is the potential degradations undergone by the biological tissue, which
      may limit the durability of the valve once implanted. The purpose of the present
      work is to study the effect of low diameter crimping on the mechanical
      performances of pericardium valve prototypes. The prototypes were compressed to a
      diameter of 1mm within braided stents for 20 min. SEM observations performed on
      crimped material show that crimped leaflets undergo degradations characterized by
      apparent surface defects. Moreover mechanical extension tests were performed on
      pericardium strips before and after crimping. The strips (15 mm long, 5mm wide)
      were taken from both crimped and native leaflets considering 2 different valve
      diameters, 19 and 21 mm. In order to prevent the premature drying of the
      pericardium tissue during the procedure, the biological tissue was kept in
      contact with a formaldehyde solution. Results show that the ultimate strength
      value decreases nearly by up to 50%. The modifications observed in the material
      may jeopardize the long term durability of the device. However, further tests are
      necessary with a larger amount of samples to confirm these early results.

PMID- 25621852
TI  - A simple access to transition metal cyclopropenylidene complexes.
AB  - We report the first example of BAC-Cu complex (BAC =
      bis(diisopropylamino)cyclopropenylidene) and its use as a carbene-transfer
      reagent, allowing access to Au-, Pd-, Ir- and Rh-BAC compounds. Catalytic
      experiments show the high activity of the [CuCl(BAC)] complex in Click chemistry.

PMID- 25621853
TI  - Anti-inflammatory coumarin and benzocoumarin derivatives from Murraya alata.
AB  - Two new rare 8-methylbenzo[h]coumarins, muralatins A and B (1, 2), nine new C-8
      substituted coumarins, muralatins C-K (3-11), and 22 known analogues (12-33) were
      isolated from the leaves of Murraya alata. The absolute configurations of
      compounds 5, 11, 23, 24, 27, 30, and 33 were assigned via comparison of their
      specific rotations, by Mosher's method, and by single-crystal X-ray diffraction
      and electronic circular dichroism (ECD) data of the in situ formed transition
      metal complexes. A putative biosynthesis pathway to 1 and 2 is proposed, and the
      chemical synthesis of 1 was accomplished through electrocyclization of 5,7
      dimethoxy-8-[(Z)-3-methylbut-1,3-dienyl)]coumarin (12). Compounds 1, 2, 8, 12,
      and 31 showed inhibition of nitric oxide production in lipopolysaccharide-induced
      RAW 264.7 macrophages with IC50 values of 6.0-14.5 MUM. 

PMID- 25621854
TI  - Liquid marbles prepared from pH-responsive self-assembled micelles.
AB  - In this study, we report the assembly of amphiphilic polymeric micelles at the
      liquid/air interface to prepare liquid marbles for the first time. The polymeric
      micelles were synthesized from the self-assembly of a fluoropolymer, poly(styrene
      co-acrylic acid-co-2,2,3,4,4,4-hexafluorobutyl methacrylate), in a selective
      solvent. The particle size, morphology and chemical composition of the micelles
      were determined by dynamic light scattering (DLS), transmission electron
      microscopy, scanning electron microscopy and X-ray photoelectron spectroscopy.
      DLS and aqueous electrophoresis revealed the pH-responsiveness of the micelles in
      aqueous dispersion. Liquid marbles with water volumes varying from 10 MUL to 1 mL
      were formed by rolling water droplets on the micelle powder bed. The increase in
      water volume led to the shape transition of the liquid marbles from quasi
      spherical to a puddle-like shape because of gravity. Fluorescence microscopy was
      used to observe the morphology of the formed liquid marbles, which confirmed that
      the micelles were adsorbed at the interface of water and air. The effective
      surface tension of the liquid marbles decreased with the increasing concentration
      of NaOH, which was added to the interior water phase. This agreed with the
      results of droplet roller experiments: the mechanical integrity of the liquid
      marbles prepared from alkaline solution (pH 10) was relatively poorer than those
      prepared from acidic solution (pH 2). Moreover, these liquid marbles coated with
      micelles showed pH-responsiveness when transferred onto the surfaces of aqueous
      solutions with different pH values. The liquid marbles were relatively stable on
      the acidic solution, whereas they burst immediately on the alkaline solution with
      a pH of 10. In addition, apart from water, Gellan gum solution and glycerol could
      be also successfully encapsulated by the fluorinated micelles to form stable
      liquid marbles. 

PMID- 25621855
TI  - Electronystagmography and Videonystagmography (ENG/VNG).

PMID- 25621856
TI  - Affective and physiological responses to the suffering of others: compassion and
      vagal activity.
AB  - Compassion is an affective response to another's suffering and a catalyst of
      prosocial behavior. In the present studies, we explore the peripheral
      physiological changes associated with the experience of compassion. Guided by
      long-standing theoretical claims, we propose that compassion is associated with
      activation in the parasympathetic autonomic nervous system through the vagus
      nerve. Across 4 studies, participants witnessed others suffer while we recorded
      physiological measures, including heart rate, respiration, skin conductance, and
      a measure of vagal activity called respiratory sinus arrhythmia (RSA).
      Participants exhibited greater RSA during the compassion induction compared with
      a neutral control (Study 1), another positive emotion (Study 2), and a prosocial
      emotion lacking appraisals of another person's suffering (Study 3). Greater RSA
      during the experience of compassion compared with the neutral or control emotion
      was often accompanied by lower heart rate and respiration but no difference in
      skin conductance. In Study 4, increases in RSA during compassion positively
      predicted an established composite of compassion-related words, continuous self
      reports of compassion, and nonverbal displays of compassion. Compassion, a core
      affective component of empathy and prosociality, is associated with heightened
      parasympathetic activity.

PMID- 25621857
TI  - What a_____ thing to do! Formally characterizing actions by their expected
      effects.
AB  - A number of personality frameworks assume traits describe central tendencies of
      action--for instance, calling someone assertive indicates they have a tendency to
      perform assertive actions. But what makes it appropriate to characterize an
      action by terms like assertive, kind, or honest? We propose that actions are
      characterized by such terms in large part by having expected effects on the
      environment which match particular conceptual templates. In the present studies,
      we attempt to better identify the expected effect dimensions perceivers seem to
      utilize to make action characterizations related to the Big Five and HEXACO
      personality dimensions. To do so, a set of 150 situation-action scenarios were
      generated from actions suggestive of conscientiousness-related characteristics
      (Study 1), and of characteristics in other HEXACO domains (Study 2). Participants
      then characterized each action on a range of bipolar dimensions (e.g., assertive
      vs. submissive). A separate group of raters coded the expected effects of
      performing these actions on 21 different outcomes (e.g., effort expenditure;
      achievement of career goals). Action characterizations were highly predicted by
      expected effect dimensions in ways that matched provisional hypotheses and were
      consistent across studies. Furthermore, actions characterizations tended to be
      highly diagnostic of self-reported individual differences in the same
      characteristics. We discuss implications for a range of phenomena, such as
      understanding the relations between behaviors and traits, integrating trait
      models and decision-making models, and understanding the effect of situational
      features on personality traits.

PMID- 25621858
TI  - Social class, power, and selfishness: when and why upper and lower class
      individuals behave unethically.
AB  - Are the rich more unethical than the poor? To answer this question, the current
      research introduces a key conceptual distinction between selfish and unethical
      behavior. Based on this distinction, the current article offers 2 novel findings
      that illuminate the relationship between social class and unethical behavior.
      First, the effects of social class on unethical behavior are not invariant;
      rather, the effects of social class are moderated by whether unethical behavior
      benefits the self or others. Replicating past work, social class positively
      predicted unethical behavior; however, this relationship was only observed when
      that behavior was self-beneficial. When unethical behavior was performed to
      benefit others, social class negatively predicted unethical behavior; lower class
      individuals were more likely than upper class individuals to engage in unethical
      behavior. Overall, social class predicts people's tendency to behave selfishly,
      rather than predicting unethical behavior per se. Second, individuals' sense of
      power drove the effects of social class on unethical behavior. Evidence for this
      relationship was provided in three forms. First, income, but not education level,
      predicted unethical behavior. Second, feelings of power mediated the effect of
      social class on unethical behavior, but feelings of status did not. Third, two
      distinct manipulations of power produced the same moderation by self-versus-other
      beneficiary as was found with social class. The current theoretical framework and
      data both synthesize and help to explain a range of findings in the social class
      and power literatures.

PMID- 25621859
TI  - Optical phonons in twisted bilayer graphene with gate-induced asymmetric doping.
AB  - Twisted bilayer graphene (tBLG) devices with ion gel gate dielectrics are studied
      using Raman spectroscopy in the twist angle regime where a resonantly enhanced G
      band can be observed. We observe prominent splitting and intensity quenching on
      the G Raman band when the carrier density is tuned away from charge neutrality.
      This G peak splitting is attributed to asymmetric charge doping in the two
      graphene layers, which reveals individual phonon self-energy renormalization of
      the two weakly coupled layers of graphene. We estimate the effective interlayer
      capacitance at low doping density of tBLG using an interlayer screening model.
      The anomalous intensity quenching of both G peaks is ascribed to the suppression
      of resonant interband transitions between the two saddle points (van Hove
      singularities) that are displaced in the momentum space by gate-tuning. In
      addition, we observe a softening (hardening) of the R Raman band, a superlattice
      induced phonon mode in tBLG, in electron (hole) doping. Our results demonstrate
      that gate modulation can be used to control the optoelectronic and vibrational
      properties in tBLG devices. 

PMID- 25621860
TI  - DNA-Linked Enzyme-Coupled Assay for Probing Glucosyltransferase Specificity.
AB  - Traditional enzyme characterization methods are low-throughput and therefore
      limit engineering efforts in synthetic biology and biotechnology. Here, we
      propose a DNA-linked enzyme-coupled assay (DLEnCA) to monitor enzyme reactions in
      a high-throughput manner. Throughput is improved by removing the need for protein
      purification and by limiting the need for liquid chromatography mass spectrometry
      (LCMS) product detection by linking enzymatic function to DNA modification. We
      demonstrate the DLEnCA methodology using glucosyltransferases as an illustration.
      The assay utilizes cell free transcription/translation systems to produce enzymes
      of interest, while UDP-glucose and T4-beta-glucosyltransferase are used to modify
      DNA, which is detected postreaction using qPCR or a similar means of DNA
      analysis. OleD and two glucosyltransferases from Arabidopsis were used to verify
      the assay's generality toward glucosyltransferases. We further show DLEnCA's
      utility by mapping out the substrate specificity for these enzymes. 

PMID- 25621861
TI  - Primary intrinsic chiasmal germinoma.
AB  - Intracranial germinomas are typically present in the suprasellar or pineal
      location, and their origin within the optic nerve or chiasm is extremely rare. We
      report a 25-year-old woman with an exophytic primary optic chiasm germinoma who
      underwent partial resection followed by radiation and had no detectable tumor on
      magnetic resonance imaging at 1-year follow-up. 

PMID- 25621862
TI  - Bitemporal hemianopia secondary to nasal staphylomata.

PMID- 25621863
TI  - Midbrain infarction presenting with monocular elevation palsy and ptosis:
      topographic lesion analysis.
AB  - A combination of monocular elevation palsy and ptosis is usually characteristic
      of an extra-axial lesion of the superior branch of the third nerve. We report an
      unusual case of monocular elevation palsy and ipsilateral ptosis due to midbrain
      infarction involving the third nerve fascicle. In addition, we conducted a review
      of the literature of similar cases and produced an overlay image of the magnetic
      resonance scans from these reports. The overlapping regions primarily were
      located in the midbrain between the red nucleus and cerebral peduncle. This
      correlated with involvement of the lateral portion of the third nerve fascicle
      containing fibers to the superior rectus and levator palpebrae. 

PMID- 25621864
TI  - Directed evolution combined with synthetic biology strategies expedite semi
      rational engineering of genes and genomes.
AB  - Owing to our limited understanding of the relationship between sequence and
      function and the interaction between intracellular pathways and regulatory
      systems, the rational design of enzyme-coding genes and de novo assembly of a
      brand-new artificial genome for a desired functionality or phenotype are
      difficult to achieve. As an alternative approach, directed evolution has been
      widely used to engineer genomes and enzyme-coding genes. In particular,
      significant developments toward DNA synthesis, DNA assembly (in vitro or in
      vivo), recombination-mediated genetic engineering, and high-throughput screening
      techniques in the field of synthetic biology have been matured and widely
      adopted, enabling rapid semi-rational genome engineering to generate variants
      with desired properties. In this commentary, these novel tools and their
      corresponding applications in the directed evolution of genomes and enzymes are
      discussed. Moreover, the strategies for genome engineering and rapid in vitro
      enzyme evolution are also proposed. 

PMID- 25621865
TI  - A 20-year-old man with back pain and lower extremity weakness.
AB  - A 20-year-old man presented with 1 week of low back pain and progressive lower
      extremity weakness. Results of cerebrospinal fluid analysis demonstrated elevated
      total protein and a mildly elevated white blood cell count with lymphocytic
      predominance. Findings from imaging studies revealed a multifocal,
      heterogeneously enhancing, intramedullary lesion involving the cervicothoracic
      spinal cord and nodular enhancement of the cauda equina. The patient eventually
      underwent spinal surgery for tissue diagnosis. The differential diagnosis,
      pathologic findings, and diagnosis are discussed. 

PMID- 25621866
TI  - Polychlorinated biphenyl congener patterns in fish near the Hanford Site
      (Washington State, USA).
AB  - It is well-known that absorption, distribution, metabolism, and excretion (ADME)
      processes in fish can alter polychlorinated biphenyl (PCB) congener patterns in
      fish, but these patterns have never been investigated using an advanced source
      apportionment tool. In this work, PCB congener patterns in freshwater fish were
      examined with positive matrix factorization (PMF). PCB congeners were quantified
      via EPA Method 1668 in fillet and carcass of six species in four study areas in
      the Columbia River near the Hanford Site. Six factors were resolved with PMF2
      software. Depletion and enhancement of PCB congeners in factors, relative to
      Aroclor 1254, suggested biotransformation (via cytochrome P450) and
      bioaccumulation in fish, respectively. Notable differences were observed among
      species and across study locations. For example, sturgeon and whitefish exhibited
      congener patterns consistent with Aroclor weathering, suggesting potential PCB
      metabolism in these species. In terms of location, average concentration of total
      PCBs for all species combined was significantly higher (P < 0.05) at Hanford 100
      and 300 areas, relative to upriver and downriver study sites. Furthermore, a
      distinct PCB signature in sturgeon and whitefish, collected at Hanford study
      areas, suggests that Hanford is a unique PCB source. 

PMID- 25621869
TI  - Retrieval induces forgetting, but only when nontested items compete for
      retrieval: Implication for interference, inhibition, and context reinstatement.
AB  - The mechanism responsible for retrieval-induced forgetting has been the subject
      of rigorous theoretical debate, with some researchers postulating that retrieval
      induced forgetting can be explained by interference (J. G .W. Raaijmakers & E.
      Jakab, 2013) or context reinstatement (T. R. Jonker, P. Seli, & C. M. MacLeod,
      2013), whereas others claim that retrieval-induced forgetting is better explained
      by inhibition (M. C. Anderson, 2003). A fundamental assumption of the inhibition
      account is that nonpracticed items are suppressed because they compete for
      retrieval during initial testing. In the current study, we manipulated
      competition in a novel interpolated testing paradigm by having subjects learn the
      nonpracticed items either before (high-competition condition) or after (low
      competition condition) they practiced retrieval of the target items. We found
      retrieval-induced forgetting for the nonpracticed competitors only when they were
      studied before retrieval practice. This result provides support for a critical
      assumption of the inhibition account.

PMID- 25621868
TI  - Preparation and in vitro antimicrobial activity of silver-bearing degradable
      polymeric nanoparticles of polyphosphoester-block-poly(L-lactide).
AB  - The development of well-defined polymeric nanoparticles (NPs) as delivery
      carriers for antimicrobials targeting human infectious diseases requires rational
      design of the polymer template, an efficient synthetic approach, and fundamental
      understanding of the developed NPs, e.g., drug loading/release, particle
      stability, and other characteristics. Herein, we developed and evaluated the in
      vitro antimicrobial activity of silver-bearing, fully biodegradable and
      functional polymeric NPs. A series of degradable polymeric nanoparticles (dNPs),
      composed of phosphoester and L-lactide and designed specifically for silver
      loading into the hydrophilic shell and/or the hydrophobic core, were prepared as
      potential delivery carriers for three different types of silver-based
      antimicrobials-silver acetate or one of two silver carbene complexes (SCCs).
      Silver-loading capacities of the dNPs were not influenced by the hydrophilic
      block chain length, loading site (i.e., core or shell), or type of silver
      compound, but optimization of the silver feed ratio was crucial to maximize the
      silver loading capacity of dNPs, up to ca. 12% (w/w). The release kinetics of
      silver-bearing dNPs revealed 50% release at ca. 2.5-5.5 h depending on the type
      of silver compound. In addition, we undertook a comprehensive evaluation of the
      rates of hydrolytic or enzymatic degradability and performed structural
      characterization of the degradation products. Interestingly, packaging of the
      SCCs in the dNP-based delivery system improved minimum inhibitory concentrations
      up to 70%, compared with the SCCs alone, as measured in vitro against 10
      contemporary epidemic strains of Staphylococcus aureus and eight uropathogenic
      strains of Escherichia coli. We conclude that these dNP-based delivery systems
      may be beneficial for direct epithelial treatment and/or prevention of ubiquitous
      bacterial infections, including those of the skin and urinary tract.

PMID- 25621870
TI  - The tip-of-the-tongue heuristic: How tip-of-the-tongue states confer
      perceptibility on inaccessible words.
AB  - This study shows that the presence of a tip-of-the-tongue (TOT) state--the sense
      that a word is in memory when its retrieval fails--is used as a heuristic for
      inferring that an inaccessible word has characteristics that are consistent with
      greater word perceptibility. When reporting a TOT state, people judged an
      unretrieved word as more likely to have previously appeared darker and clearer
      (Experiment 1a), and larger (Experiment 1b). They also judged an unretrieved word
      as more likely to be a high frequency word (Experiment 2). This was not because
      greater fluency or word perceptibility at encoding led to later TOT states:
      Increased fluency or perceptibility of a word at encoding did not increase the
      likelihood of a TOT state for it when its retrieval later failed; moreover, the
      TOT state was not diagnostic of an unretrieved word's fluency or perceptibility
      when it was last seen. Results instead suggest that TOT states themselves are
      used as a heuristic for inferring the likely characteristics of unretrieved
      words. During the uncertainty of retrieval failure, TOT states are a source of
      information on which people rely in reasoning about the likely characteristics of
      the unretrieved information, choosing characteristics that are consistent with
      greater fluency of processing.

PMID- 25621867
TI  - Adult neurogenesis in humans- common and unique traits in mammals.
AB  - New neurons are continuously generated in specific regions in the adult brain.
      Studies in rodents have demonstrated that adult-born neurons have specific
      functional features and mediate neural plasticity. Data on the extent and
      dynamics of adult neurogenesis in adult humans are starting to emerge, and there
      are clear similarities and differences compared to other mammals. Why do these
      differences arise? And what do they mean? 

PMID- 25621871
TI  - A case of hypotrichosis with juvenile macular dystrophy.
AB  - PURPOSE: To report a very rare case of hypotrichosis with juvenile macular
      dystrophy. METHODS: Clinical case report and literature review. RESULTS: A 6-year
      old boy was referred to us for a retinal evaluation after retinal defects were
      found bilaterally by his optometrist. His ocular symptoms included decreased
      visual acuity and light sensitivity. His ocular history was unremarkable. Review
      of systems was positive for hypotrichosis. Fundus examination revealed bull's eye
      maculopathy bilaterally. The patient was found to have a cadherin-3 genetic
      defect, which is associated with hypotrichosis with juvenile macular dystrophy.
      In follow-up, fundus autofluorescence revealed severe hypoautofluorescence with
      severe retinal pigment epithelium loss, and spectral domain optical coherence
      tomography showed evidence of retinal pigment epithelium, photoreceptor, and
      inner segment/outer segment disruption bilaterally. CONCLUSION: Hypotrichosis
      with juvenile macular dystrophy is a very rare genetic disorder that should be in
      the differential for macular degeneration during the first 4 decades of life. A
      detailed review of systems should always be performed on these patients.

PMID- 25621872
TI  - Toxoplasma chorioretinitis diagnosed by histopathology in a patient with AIDS.
AB  - PURPOSE: To demonstrate the diagnostic difficulties in cases of retinal necrosis
      in immunocompromised patients including the potential for false-negative anterior
      segment sampling and also to emphasize the utility of diagnostic vitrectomy with
      histopathologic examination. METHODS: This patient's chart was thoroughly
      reviewed to present salient features that are relevant to any ophthalmologist
      attempting to diagnose and treat chorioretinitis. A 38-year-old man with HIV/AIDS
      who presented with bilateral retinal necrosis. Thorough workup, including
      multiple samples of anterior chamber fluid for polymerase chain reaction, was
      negative. RESULTS: Diagnostic vitrectomy revealed a toxoplasma cyst. Triple
      therapy stabilized retinitis, although vision did not improve. CONCLUSION: This
      case reminds the clinician to consider a broad differential diagnosis for retinal
      necrosis in immunocompromised hosts and, when serologic and anterior chamber
      samples are negative, to consider diagnostic vitrectomy for polymerase chain
      reaction and histopathologic examination.

PMID- 25621873
TI  - Photocontrolled nitric oxide release from two nitrosylruthenium isomer complexes
      and their potential biomedical applications.
AB  - Nitric oxide (NO) has key regulatory roles in various biological and medical
      processes. The control of its local concentration, which is crucial for obtaining
      the desired effect, can be achieved with exogenous NO donors. Release of NO from
      metal-nitrosyl complexes upon exposure to light is a strategy that could allow
      for the site-specific delivery of the reactive species NO to physiological
      targets. The photodissociation of NO from two nitrosylruthenium(II) isomer
      complexes {cis- and trans-[Ru(OAc)(2mqn)(2)NO]} was demonstrated by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry spectra,
      and electron paramagnetic resonance spectra further prove the photoinduced NO
      release by spin trapping of NO free radicals upon photoirradiation. Real-time NO
      release was quantitatively measured by electrochemistry with an NO-specific
      electrode. The quantitative control of NO release from [Ru(OAc)(2mqn)(2)NO] in
      aqueous solutions was done by photoirradiation at different wavelengths. Both
      isomers show photoinduced damage on plasmid DNA, but the trans isomer has higher
      cytotoxicity and photocytotoxicity activity against the HeLa tumor cell line than
      that of the cis isomer. Nitrosylruthenium(II) complex, with 8-quinolinol
      derivatives as ligands, has a great potential as a photoactivated NO donor
      reagent for biomedical applications.

PMID- 25621875
TI  - The role of computed tomography angiography in patients undergoing evaluation for
      minimally invasive cardiac surgery: an early program experience.
AB  - OBJECTIVE: An increasing number of patients are undergoing surgical procedures
      using minimally invasive cardiac surgery (MICS). These techniques use
      conventional or retrograde arterial perfusion with direct aortic cross-clamping
      or endoballoon occlusion. Precise knowledge of the arterial tree is required to
      avoid complications and to plan for the operation. We examined the role of
      computed tomography angiography (CTA) in evaluating patients for MICS. METHODS:
      We reviewed all consecutive candidates undergoing CTA during preoperative
      evaluation for MICS aortic, mitral, tricuspid, Maze, atrial septal defect, or
      myxoma procedures between February 2008 and May 2010. The CTA findings of
      patients excluded from MICS were compared against those successfully undergoing
      MICS. RESULTS: One hundred eleven MICS candidates underwent preoperative CTA.
      Thirty-five (32%) had single or multiple CTA findings precluding MICS and
      underwent sternotomy. Seventy-six (68%) had favorable CTA findings and underwent
      MICS. The MICS group had a mean age of 62 years, with 29 women (39%); the non
      MICS group had a mean age of 68 years, with 17 women (48%). Of the patients
      excluded from MICS, two (6%) had diminished or absent lower extremity pulses. All
      MICS patients (except for aortic) had successful use of the endoballoon. There
      were no perfusion or peripheral vascular complications. There was one stroke, one
      lymphocele, and one death (chronic obstructive pulmonary disease exacerbation).
      CONCLUSIONS: Computed tomography angiography is of fundamental importance in
      evaluating patients for MICS. It can identify calcified regions that make for
      threatening catheter passage with subsequent retrograde arterial perfusion.
      Abnormalities of the arterial tree are identified. The use of CTA-guided patient
      selection can thus avoid major perioperative complications.

PMID- 25621874
TI  - MALDI Imaging mass spectrometry: current frontiers and perspectives in pathology
      research and practice.
AB  - MALDI Imaging mass spectrometry has entered the field of tissue-based research by
      providing unique advantages for analyzing tissue specimen in an unprecedented
      detail. A broad spectrum of analytes ranging from proteins, peptides, protein
      modification over small molecules, drugs and their metabolites as well as
      pharmaceutical components, endogenous cell metabolites, lipids, and other
      analytes are made accessible by this in situ technique in tissue. Some of them
      were even not accessible in tissues within the histological context before.
      Thereby, the great advantage of MALDI Imaging is the correlation of molecular
      information with traditional histology by keeping the spatial localization
      information of the analytes after mass spectrometric measurement. This method is
      label-free and allows multiplex analysis of hundreds to thousands of molecules in
      the very same tissue section simultaneously. Imaging mass spectrometry brings a
      new quality of molecular data and links the expert discipline of pathology and
      deep molecular mass spectrometric analysis to tissue-based research. This review
      will focus on state-of-the-art of MALDI Imaging mass spectrometry, its recent
      applications by analyzing tissue specimen and the contributions in understanding
      the biology of disease as well as its perspectives for pathology research and
      practice. 

PMID- 25621876
TI  - Use of a ventricular septal defect occluder for apical closure in transapical
      aortic valve replacement.
AB  - During transapical transcatheter aortic valve replacement (TA-TAVR), the apical
      closure remains a challenge for the surgeon, having the risk for ventricular tear
      and massive bleeding. Apical closure devices are already under clinical
      evaluation, but only a few can lead to a full percutaneous TA-TAVR. We describe
      the successful use of a 9-mm myocardial occluder (ventricular septal defect
      occluder) that was used to seal the apex after a standard TA-TAVR (using the
      Sapien XT 23-mm transcatheter valve and the Ascendra + delivery system). The
      placement of the nonmodified myocardial occluder was performed through the
      Ascendra + delivery system, with a very small amount of blood loss and an
      acceptable sealing of the apical tear. This approach is feasible and represents a
      further step toward true-percutaneous transapical heart valve procedures.
      Modified apical occluders are under evaluation in animal models. 

PMID- 25621877
TI  - Exposures of lateral and inferior cardiac surface for coronary anastomosis during
      minimally invasive coronary artery bypass grafting.
AB  - Exposure of the lateral and inferior surface of the heart during off-pump
      coronary artery bypass grafting is associated with some degree of cardiac
      instability during recovery with completion of grafting. Exposure of lateral and
      posterior surfaces by currently available equipment is difficult in minimally
      invasive coronary artery bypass grafting (MICABG) owing to limited exposure. We
      describe an effective variation of often-used technique of pericardial stitch in
      exposure of cardiac surfaces during MICABG. This technique was used in 24
      patients undergoing multivessel MICABG. Deep pericardial sutures were used to
      manipulate the exposure of cardiac surfaces. Left anterior descending artery was
      grafted in all 24 cases. Obtuse marginal artery was grafted in 20 cases and
      posterior descending artery in 12 cases. Average grafts were 2.3 per patient.
      There was no conversion to median sternotomy. Use of deep pericardial suture is
      simple technique for exposure of lateral and inferior surface during multivessel
      MICABG. This offers adequate exposure and operating space for easy
      maneuverability. 

PMID- 25621878
TI  - Effects of chemical oxidants on perfluoroalkyl acid transport in one-dimensional
      porous media columns.
AB  - In situ chemical oxidation (ISCO) is a remediation approach that is often used to
      remediate soil and groundwater contaminated with fuels and chlorinated solvents.
      At many aqueous film-forming foam-impacted sites, perfluoroalkyl acids (PFAAs)
      can also be present at concentrations warranting concern. Laboratory experiments
      were completed using flow-through one-dimensional columns to improve our
      understanding of how ISCO (i.e., activated persulfate, permanganate, or catalyzed
      hydrogen peroxide) could affect the fate and transport of PFAAs in saturated
      porous media. While the resultant data suggest that standard ISCO is not a viable
      remediation strategy for PFAA decomposition, substantial changes in PFAA
      transport were observed upon and following the application of ISCO. In general,
      activated persulfate decreased PFAA transport, while permanganate and catalyzed
      hydrogen peroxide increased PFAA transport. PFAA sorption increased in the
      presence of increased aqueous polyvalent cation concentrations or decreased pH.
      The changes in contaminant mobility were greater than what would be predicted on
      the basis of aqueous chemistry considerations alone, suggesting that the
      application of ISCO results in changes to the porous media matrix (e.g., soil
      organic matter quality) that also influence transport. The application of ISCO is
      likely to result in changes in PFAA transport, where the direction (increased or
      decreased transport) and magnitude are dependent on PFAA characteristics, oxidant
      characteristics, and site-specific factors. 

PMID- 25621880
TI  - Wide complex tachycardia recorded with a smartphone cardiac rhythm monitor.

PMID- 25621879
TI  - Organization of enzyme concentration across the metabolic network in cancer
      cells.
AB  - Rapid advances in mass spectrometry have allowed for estimates of absolute
      concentrations across entire proteomes, permitting the interrogation of many
      important biological questions. Here, we focus on a quantitative aspect of human
      cancer cell metabolism that has been limited by a paucity of available data on
      the abundance of metabolic enzymes. We integrate data from recent measurements of
      absolute protein concentration to analyze the statistics of protein abundance
      across the human metabolic network. At a global level, we find that the enzymes
      in glycolysis comprise approximately half of the total amount of metabolic
      proteins and can constitute up to 10% of the entire proteome. We then use this
      analysis to investigate several outstanding problems in cancer metabolism,
      including the diversion of glycolytic flux for biosynthesis, the relative
      contribution of nitrogen assimilating pathways, and the origin of cellular redox
      potential. We find many consistencies with current models, identify several
      inconsistencies, and find generalities that extend beyond current understanding.
      Together our results demonstrate that a relatively simple analysis of the
      abundance of metabolic enzymes was able to reveal many insights into the
      organization of the human cancer cell metabolic network. 

PMID- 25621881
TI  - A case-control study of sudden unexplained nocturnal death syndrome in the
      southern Chinese Han population.
AB  - To study the epidemiological characteristics of sudden unexplained nocturnal
      death syndrome (SUNDS) in the southern Chinese Han population during 2007 to
      2013, we gathered 879 SUNDS victims from Dongguan City and in the Longgang
      District in Shenzhen City as the case group then selected 879 all-cause death
      cases, adopting a 1:1 pair method, as the control group I and collected 8142 all
      cause death cases from the Bao'an District in Shenzhen City as the control group
      II, simultaneously. Case information collected was statistically analyzed. The
      annual incidence of SUNDS is 1.02 and 2.23 per 100,000 person-years for Dongguan
      City and in the Longgang District, respectively. The number of male and female
      victims is drastically different, with a ratio of 13.92:1, whereas the incidence
      between the 2 sexes is significantly different (chi2 = 78.734, P < 0.01), with an
      odds ratio value of 11.32 (95% confidence interval, 5.75-22.28). The age of death
      of SUNDS cases ranges from 17 to 55 years with a median age of 35 years;
      furthermore, the difference of distribution of age of death between the SUNDS
      victims and the all-cause death population is significant (chi2 = 767.12, P <
      0.001). The birthplace of SUNDS victims is distributed throughout 27 provinces of
      China, but the difference between the SUNDS victims and the all-cause death
      population is not significant (chi2 = 27.273, P > 0.05). The monthly incidence of
      SUNDS is relatively higher from March to June, whereas the difference of monthly
      distribution between SUNDS victims and all-cause death population is significant
      (chi2 = 9.869, P < 0.05), with an odds ratio value of 1.42 (95% confidence
      interval, 1.14-1.76). Although the majority of SUNDS occurred during midnight
      sleep, they were mostly discovered from 7 to 9 am once the inmates or spouses
      woke in the morning. A total of 97.74% of the SUNDS victims were blue-collar
      factory workers with a high-intensity labor and poor education background. This
      investigation confirmed the stability of epidemiological characteristics of SUNDS
      in South China and implicated that risk factors of this fatal disease still
      exist. The efficient strategy of early identification such as molecular diagnosis
      for SUNDS is extremely urgently required.

PMID- 25621882
TI  - Social ties and psychological well-being in late life: the mediating role of
      relationship satisfaction.
AB  - OBJECTIVE: The current paper examines whether quantitative aspects of social
      support (i.e., support network characteristics) indirectly influence
      psychological well-being via older adults' qualitative perceptions of support
      (i.e., satisfaction with social relationships). METHODS: A sample of 416 adults
      aged >=60 was drawn from the Social Integration and Aging Study, a community
      based survey conducted in a small US (Midwestern) city. The survey assessed
      social networks, social support, and physical and mental health among older
      adults. RESULTS: Bootstrapping was used to examine mediation models. Greater
      support network size predicted lower perceived stress, fewer depressive symptoms,
      and better life satisfaction, yet this association was fully mediated by
      relationship satisfaction. For support network composition, greater proportion
      kin was associated with lower stress and better life satisfaction, though not
      depressive symptoms, however, relationship satisfaction did not mediate this
      link. DISCUSSION: Findings highlight the complex interplay of support network
      characteristics and satisfaction, and suggest the greater import of support
      satisfaction for older adults' psychological well-being.

PMID- 25621883
TI  - Correction: galectin-3 as a marker and potential therapeutic target in breast
      cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0103482.]. 

PMID- 25621885
TI  - Community investment in wind farms: funding structure effects in wind energy
      infrastructure development.
AB  - Wind energy development is an increasingly popular form of renewable energy
      infrastructure in rural areas. Communities generally perceive socioeconomic
      benefits accrue and that community funding structures are preferable to corporate
      structures, yet lack supporting quantitative data to inform energy policy. This
      study uses the Everpower wind development, to be located in Midwestern Ohio, as a
      hypothetical modeling environment to identify and examine socioeconomic impact
      trends arising from corporate, community and diversified funding structures.
      Analysis of five National Renewable Energy Laboratory Jobs and Economic
      Development Impact models incorporating local economic data and review of
      relevant literature were conducted. The findings suggest that community and
      diversified funding structures exhibit 40-100% higher socioeconomic impact levels
      than corporate structures. Prioritization of funding sources and retention of
      federal tax incentives were identified as key elements. The incorporation of
      local shares was found to mitigate the negative effects of foreign private
      equity, local debt financing increased economic output and opportunities for
      private equity investment were identified. The results provide the groundwork for
      energy policies focused to maximize socioeconomic impacts while creating
      opportunities for inclusive economic participation and improved social acceptance
      levels fundamental to the deployment of renewable energy technology. 

PMID- 25621884
TI  - Immunogenicity and safety of cell-derived MF59(r)-adjuvanted A/H1N1 influenza
      vaccine for children.
AB  - Mass immunization of children has the potential to decrease infection rates and
      prevent the transmission of influenza. We evaluated the immunogenicity, safety,
      and tolerability of different formulations of cell-derived MF59-adjuvanted and
      nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a
      randomized, single-blind, multicenter study with a total of 666 healthy subjects
      aged 6 months-17 y in one of 3 vaccination groups, each receiving formulations
      containing different amounts of influenza A/H1N1 antigen with or without MF59. A
      booster trivalent seasonal MF59 vaccine was administered one year after primary
      vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI)
      and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks
      post booster). Safety was monitored throughout the study. One vaccination with
      3.75 MUg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 MUg of
      A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer
      >=1:40 in >70% of children in the 1-<3, 3-8, and 9-17 y cohorts; however, 2
      vaccinations with nonadjuvanted 15 MUg A/H1N1 antigen were needed to achieve this
      response in the 1-<3 and 3-8 y cohorts. Among children aged 6-11 months, 1 dose
      of 7.5_fullMF59 resulted in an HI titer >=1:40 in >70% while 2 doses of
      3.75_halfMF59 were required to achieve this result. All vaccines were well
      tolerated. Our findings support the immunogenicity and safety of the
      3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine
      formulations for use in children and adolescents aged 6 months to 17 y The use of
      the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing,
      increasing the available vaccine doses allowing vaccination of more people. 

PMID- 25621886
TI  - Performance of genotype imputation for low frequency and rare variants from the
      1000 genomes.
AB  - Genotype imputation is now routinely applied in genome-wide association studies
      (GWAS) and meta-analyses. However, most of the imputations have been run using
      HapMap samples as reference, imputation of low frequency and rare variants (minor
      allele frequency (MAF) < 5%) are not systemically assessed. With the emergence of
      next-generation sequencing, large reference panels (such as the 1000 Genomes
      panel) are available to facilitate imputation of these variants. Therefore, in
      order to estimate the performance of low frequency and rare variants imputation,
      we imputed 153 individuals, each of whom had 3 different genotype array data
      including 317k, 610k and 1 million SNPs, to three different reference panels: the
      1000 Genomes pilot March 2010 release (1KGpilot), the 1000 Genomes interim August
      2010 release (1KGinterim), and the 1000 Genomes phase1 November 2010 and May 2011
      release (1KGphase1) by using IMPUTE version 2. The differences between these
      three releases of the 1000 Genomes data are the sample size, ancestry diversity,
      number of variants and their frequency spectrum. We found that both reference
      panel and GWAS chip density affect the imputation of low frequency and rare
      variants. 1KGphase1 outperformed the other 2 panels, at higher concordance rate,
      higher proportion of well-imputed variants (info>0.4) and higher mean info score
      in each MAF bin. Similarly, 1M chip array outperformed 610K and 317K. However for
      very rare variants (MAF <= 0.3%), only 0-1% of the variants were well imputed. We
      conclude that the imputation of low frequency and rare variants improves with
      larger reference panels and higher density of genome-wide genotyping arrays. Yet,
      despite a large reference panel size and dense genotyping density, very rare
      variants remain difficult to impute.

PMID- 25621887
TI  - Boosting performance of low temperature fuel cell catalysts by subtle ionic
      liquid modification.
AB  - High cost and poor stability of the oxygen reduction reaction (ORR)
      electrocatalysts are the major barriers for broad-based application of polymer
      electrolyte membrane fuel cells. Here we report a facile and scalable approach to
      improve Pt/C catalysts for ORR, by modification with small amounts of hydrophobic
      ionic liquid (IL). The ORR performance of these IL-modified catalysts can be
      readily manipulated by varying the degree of IL filling, leading to a 3.4 times
      increase in activity. Besides, the IL-modified catalysts exhibit substantially
      enhanced stability relative to Pt/C. The enhanced performance is attributed to
      the optimized microenvironment at the interface of Pt and electrolyte, where
      advantages stemming from an increased number of free sites, higher oxygen
      concentration in the IL and electrostatic stabilization of the nanoparticles
      develop fully, at the same time that the drawback of mass transfer limitation
      remains suppressed. These findings open a new avenue for catalyst optimization
      for next-generation fuel cells. 

PMID- 25621888
TI  - Copper-catalyzed hydroalkylation of terminal alkynes.
AB  - We have developed a copper-catalyzed hydroalkylation of terminal alkynes using
      alkyl triflates as coupling partners and (Me(2)HSi)(2)O as a hydride donor. The
      hydroalkylation proceeds with excellent anti-Markovnikov regioselectivity and
      provides exclusively (E)-alkenes. We have demonstrated that both alkyl- and aryl
      substituted alkynes can be used as substrates, together with 1 degrees  alkyl and
      benzylic triflates. Finally, the transformation can be accomplished in the
      presence of a wide range of functional groups. Overall, the new hydroalkylation
      reaction allows highly efficient and diastereospecific synthesis of (E)-alkenes
      from readily available terminal alkynes and alkyl triflates. On the basis of a
      preliminary mechanistic study, we propose that the hydroalkylation reaction
      involves copper hydride formation, hydrocupration of an alkyne, and alkylation of
      an alkenyl copper intermediate.

PMID- 25621890
TI  - From the editor.

PMID- 25621891
TI  - Filling pore space in a microporous coordination polymer to improve methane
      storage performance.
AB  - A strategy that allows the tuning of pore size in microporous coordination
      polymers (MCPs) through modification of their organic linkers is presented. When
      large substituents are introduced onto the linker, these pendent groups partially
      occupy the pores, thus reducing pore size while serving as additional adsorption
      sites for gases. The approach takes advantage of the fact that, for methane
      storage materials, small pores (0.4-0.8 nm in diameter) are more desirable than
      large pores since small pores promote optimal volumetric capacity. This method
      was demonstrated with IRMOF-8, a MCP constructed from Zn4O metal clusters and 2,6
      naphthalenedicarboxylate (NDC) linkers. The NDC was functionalized through the
      addition of substituents including tert-butylethynyl or phenylethynyl groups.
      High pressure methane uptake demonstrates that the IRMOF-8 derivatives have
      significantly better performance than the unfunctionalized material in terms of
      both excess volumetric uptake and deliverable capacity. Moreover, IRMOF-8
      derivatives also give rise to stronger interactions with methane molecules as
      shown by higher heat of adsorption values. 

PMID- 25621889
TI  - EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in
      diffuse gliomas.
AB  - Hypermethylation of tumor suppressor genes is one of the hallmarks in the
      progression of brain tumors. Our objectives were to analyze the presence of the
      hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas
      (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, and to
      establish their association with the patients' clinicopathological
      characteristics. Gene hypermethylation was analyzed by methylation-specific-PCR
      and confirmed by pyrosequencing (for EPB41L3 and TSP-1) and bisulfite-sequencing
      (for RASSF2). EPB41L3, RASSF2 and TSP-1 genes were hypermethylated only in tumors
      (29%, 10.6%, and 50%, respectively), confirming their cancer-specific role.
      Treatment of cells with the DNA-demethylating-agent 5-aza-2'-deoxycytidine
      restores their transcription, as confirmed by quantitative-reverse-transcription
      PCR and immunofluorescence. Immunohistochemistry for EPB41L3, RASSF2 and TSP-1
      was performed to analyze protein expression; p53, ki-67, and CD31 expression and
      1p/19q co-deletion were considered to better characterize the tumors. EPB41L3 and
      TSP-1 hypermethylation was associated with worse (p = 0.047) and better (p =
      0.037) prognosis, respectively. This observation was confirmed after adjusting
      the results for age and tumor grade, the role of TSP-1 being most pronounced in
      oligodendrogliomas (p = 0.001). We conclude that EPB41L3, RASSF2 and TSP-1 genes
      are involved in the pathogenesis of diffuse gliomas, and that EPB41L3 and TSP-1
      hypermethylation are of prognostic significance. 

PMID- 25621892
TI  - Solubility Limits in Lennard-Jones Mixtures: Effects of Disparate Molecule
      Geometries.
AB  - In order to better understand general effects of the size and energy disparities
      between macromolecules and solvent molecules in solution, especially for
      macromolecular constructs self-assembled from smaller molecules, we use the first
      and second-order exact bridge diagram extensions of the HNC integral equation
      theory to investigate single-component, binary, ternary, and quaternary mixtures
      of Lennard-Jones fluids. For pure fluids, we find that the HNCH3 bridge function
      integral equation (i.e., exact to third order in density) is necessary to
      quantitatively predict the pure gas and pure liquid sides of the coexistence
      region of the phase diagram of the Lennard-Jones fluid. For the mixtures, we find
      that the HNCH2 bridge function integral equation is sufficient to qualitatively
      predict solubility in the binary, ternary, and quaternary mixtures, up to the
      nominal solubility limit. The results, as limiting cases, should be useful to
      several problems, including accurate phase diagram predictions for complex
      mixtures, design of self-assembling nanostructures via solvent controls, and the
      solvent contributions to the conformational behavior of macromolecules in complex
      fluids. 

PMID- 25621894
TI  - Possible Detrimental Effects of Clamping Main Versus Segmental Renal Arteries for
      the Achievement of Renal Global Ischemia During Robot-Assisted Partial
      Nephrectomy.
AB  - PURPOSE: To determine the impacts of clamping the main renal artery vs
      individually clamping presegmental or segmental arteries at the time of global
      renal ischemia on the surgical and functional outcomes of robot-assisted partial
      nephrectomy (RAPN). PATIENTS AND METHODS: Patients who underwent RAPN at our
      center from 2009 to September 2013 were assessed for details of intraoperative
      renal arterial anatomy. Cases were divided into two groups according to the type
      of global renal ischemia: Group 1 consisted of cases where one main renal artery
      (or hilum) was clamped; group 2 included cases where multiple arteries or
      multiple branches of arteries were individually clamped. Patient demographics,
      tumor characteristics, perioperative data, functional outcomes (as well as
      pathology findings) were assessed for both groups. Univariable and multivariable
      analyses were performed for identifying factors predicting early (at day 3)
      estimated glomerular filtration rate (eGFR) preservation postoperatively.
      RESULTS: Group 1 and group 2 included 468 and 111 patients, respectively.
      Estimated blood loss and warm ischemia time (WIT) were comparable between the two
      groups. A higher proportion of combined arterial and venous clamping was observed
      in group 1 (76.2% vs 52.3%; P=0.0001). On postoperative day 3, eGFR preservation
      was not significantly different between the two groups (P=0.87). On multivariable
      analysis, WIT and preoperative eGFR remained the only significant predictors of
      early eGFR preservation. The number of arterial vessels clamped during the
      procedure or simultaneous arterial/vein clamping were not predictors of early
      eGFR preservation. CONCLUSIONS: Perioperative outcomes of RAPN are not influenced
      by clamping the main renal artery compared with clamping multiple branches of the
      renal artery for achievement of global renal ischemia. WIT and baseline eGFR were
      confirmed to be significant predictors of postoperative renal function
      preservation after RAPN.

PMID- 25621893
TI  - Compartment-specific and sequential role of MyD88 and CARD9 in chemokine
      induction and innate defense during respiratory fungal infection.
AB  - Aspergillus fumigatus forms ubiquitous airborne conidia that humans inhale on a
      daily basis. Although respiratory fungal infection activates the adaptor proteins
      CARD9 and MyD88 via C-type lectin, Toll-like, and interleukin-1 family receptor
      signals, defining the temporal and spatial pattern of MyD88- and CARD9-coupled
      signals in immune activation and fungal clearance has been difficult to achieve.
      Herein, we demonstrate that MyD88 and CARD9 act in two discrete phases and in two
      cellular compartments to direct chemokine- and neutrophil-dependent host defense.
      The first phase depends on MyD88 signaling because genetic deletion of MyD88
      leads to delayed induction of the neutrophil chemokines CXCL1 and CXCL5, delayed
      neutrophil lung trafficking, and fatal pulmonary damage at the onset of
      respiratory fungal infection. MyD88 expression in lung epithelial cells restores
      rapid chemokine induction and neutrophil recruitment via interleukin-1 receptor
      signaling. Exogenous CXCL1 administration reverses murine mortality in MyD88
      deficient mice. The second phase depends predominately on CARD9 signaling because
      genetic deletion of CARD9 in radiosensitive hematopoietic cells interrupts CXCL1
      and CXCL2 production and lung neutrophil recruitment beyond the initial MyD88
      dependent phase. Using a CXCL2 reporter mouse, we show that lung-infiltrating
      neutrophils represent the major cellular source of CXCL2 during CARD9-dependent
      recruitment. Although neutrophil-intrinsic MyD88 and CARD9 function are
      dispensable for neutrophil conidial uptake and killing in the lung, global
      deletion of both adaptor proteins triggers rapidly progressive invasive disease
      when mice are challenged with an inoculum that is sub-lethal for single adapter
      protein knockout mice. Our findings demonstrate that distinct signal transduction
      pathways in the respiratory epithelium and hematopoietic compartment partially
      overlap to ensure optimal chemokine induction, neutrophil recruitment, and fungal
      clearance within the respiratory tract. 

PMID- 25621896
TI  - Proton radiation alters intrinsic and synaptic properties of CA1 pyramidal
      neurons of the mouse hippocampus.
AB  - High-energy protons constitute at least 85% of the fluence of energetic ions in
      interplanetary space. Although protons are only sparsely ionizing compared to
      higher atomic mass ions, they nevertheless significantly contribute to the
      delivered dose received by astronauts that can potentially affect central nervous
      system function at high fluence, especially during prolonged deep space missions
      such as to Mars. Here we report on the long-term effects of 1 Gy proton
      irradiation on electrophysiological properties of CA1 pyramidal neurons in the
      mouse hippocampus. The hippocampus is a key structure for the formation of long
      term episodic memory, for spatial orientation and for information processing in a
      number of other cognitive tasks. CA1 pyramidal neurons form the last and critical
      relay point in the trisynaptic circuit of the hippocampal principal neurons
      through which information is processed before being transferred to other brain
      areas. Proper functioning of CA1 pyramidal neurons is crucial for hippocampus
      dependent tasks. Using the patch-clamp technique to evaluate chronic effects of 1
      Gy proton irradiation on CA1 pyramidal neurons, we found that the intrinsic
      membrane properties of CA1 pyramidal neurons were chronically altered at 3 months
      postirradiation, resulting in a hyperpolarization of the resting membrane
      potential (VRMP) and a decrease in input resistance (Rin). These small but
      significant alterations in intrinsic properties decreased the excitability of CA1
      pyramidal neurons, and had a dramatic impact on network function in a
      computational model of the CA1 microcircuit. We also found that proton-radiation
      exposure upregulated the persistent Na(+) current (INaP) and increased the rate
      of miniature excitatory postsynaptic currents (mEPSCs). Both the INaP and the
      heightened rate of mEPSCs contribute to neuronal depolarization and excitation,
      and at least in part, could compensate for the reduced excitability resulting
      from the radiation effects on the VRMP and the Rin. These results show long-term
      alterations in the intrinsic properties of CA1 pyramidal cells after realistic,
      low-dose proton irradiation. 

PMID- 25621895
TI  - Intermediate filament mechanics in vitro and in the cell: from coiled coils to
      filaments, fibers and networks.
AB  - Intermediate filament proteins form filaments, fibers and networks both in the
      cytoplasm and the nucleus of metazoan cells. Their general structural building
      plan accommodates highly varying amino acid sequences to yield extended dimeric
      alpha-helical coiled coils of highly conserved design. These 'rod' particles are
      the basic building blocks of intrinsically flexible, filamentous structures that
      are able to resist high mechanical stresses, that is, bending and stretching to a
      considerable degree, both in vitro and in the cell. Biophysical and computer
      modeling studies are beginning to unfold detailed structural and mechanical
      insights into these major supramolecular assemblies of cell architecture, not
      only in the 'test tube' but also in the cellular and tissue context. 

PMID- 25621897
TI  - Synthesis and glycosidase inhibition of australine and its fluorinated
      derivatives.
AB  - Australine (1), 7-epi-australine (2), and their C-7-fluorinated derivatives 4 and
      5 have been synthesized efficiently from D-arabinose-derived cyclic nitrone 11.
      Fluorination at the C-7 position enhanced the inhibition against A. niger alpha
      glucosidase, and this constitutes the first example of fluorination substitution
      for a hydroxyl increasing the inhibition of any glycosidases. The enantiomers
      synthesized from nitrone ent-11 showed no inhibition of the corresponding
      enzymes.

PMID- 25621898
TI  - The influence of emotion on face processing.
AB  - According to the broaden-and-build theory, positive emotions broaden one's
      thought-action repertoire, which may manifest as a widened attentional scope in
      cognitive processing. The present study directly tests this hypothesis by
      examining the influences of induced emotions (positive, neutral and negative) on
      holistic processing of face (Experiment 1) and face discrimination (Experiment
      2). In both experiments, emotions induced with images from the International
      Affective Picture System significantly interacted with face processing. That is,
      positive emotions engendered greater holistic face encoding in a composite-face
      task in Experiment 1 and more accurate face discrimination in Experiment 2,
      relative to the neutral condition. In contrast, negative emotions impaired
      holistic face encoding in the composite-face task and reduced face discrimination
      accuracy. Taken together, these results provide further support for the
      attentional broadening effect of positive affect by demonstrating that induced
      positive emotions facilitate holistic/configural processing. 

PMID- 25621901
TI  - Under the lens: carbon nanotube and protein interaction at the nanoscale.
AB  - The combination of the very different chemical natures of carbon nanotubes (CNTs)
      and proteins gives rise to systems with unprecedented performance, thanks to a
      rich pool of very diverse chemical, electronic, catalytic and biological
      properties. Here we review recent advances in the field, including innovative and
      imaginative aspects from a nanoscale point of view. The tubular nature of CNTs
      allows for internal protein encapsulation, and also for their external coating by
      protein cages, affording bottom-up ordering of molecules in hierarchical
      structures. To achieve such complex systems it is imperative to master the
      intermolecular forces between CNTs and proteins, including geometry effects (e.g.
      CNT diameter and curvature) and how they translate into changes in the local
      environment (e.g. water entropy). The type of interaction between proteins and
      CNTs has important consequences for the preservation of their structure and, in
      turn, function. This key aspect cannot be neglected during the design of their
      conjugation, be it covalent, non-covalent, or based on a combination of both
      methods. The review concludes with a brief discussion of the very many
      applications intended for CNT-protein systems that go across various fields of
      science, from industrial biocatalysis to nanomedicine, from innovative materials
      to biotechnological tools in molecular biology research. 

PMID- 25621899
TI  - Whole-genome sequencing of quartet families with autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for
      hundreds of susceptibility loci. Previous microarray and exome-sequencing studies
      have examined portions of the genome in simplex families (parents and one ASD
      affected child) having presumed sporadic forms of the disorder. We used whole
      genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected
      siblings), consisting of 170 individuals with ASD, to generate a comprehensive
      data resource encompassing all classes of genetic variation (including noncoding
      variants) and accompanying phenotypes, in apparently familial forms of ASD. By
      examining de novo and rare inherited single-nucleotide and structural variations
      in genes previously reported to be associated with ASD or other
      neurodevelopmental disorders, we found that some (69.4%) of the affected siblings
      carried different ASD-relevant mutations. These siblings with discordant
      mutations tended to demonstrate more clinical variability than those who shared a
      risk variant. Our study emphasizes that substantial genetic heterogeneity exists
      in ASD, necessitating the use of WGS to delineate all genic and non-genic
      susceptibility variants in research and in clinical diagnostics. 

PMID- 25621902
TI  - Health Promotion Practice and Interprofessional Education in Aging: Senior
      Wellness Fairs.
AB  - Senior wellness fairs (SWFs) offer a unique opportunity for community health
      promotion and interprofessional education (IPE). The authors describe and
      evaluate the impact of a 3-year, university-community SWF collaboration on
      interprofessional competencies among students across multiple professional
      programs. Participation in the SWF enhanced student knowledge and skills in
      providing health promotion information to older adults in an interprofessional,
      collaborative setting as indicated by mean scores on the Perceived Learning
      Outcomes Survey, an instrument developed for this project. Open-ended data
      highlighted aspects of the SWF that students found most useful (interaction with
      seniors, community resources, interprofessional learning, and self-awareness) and
      most challenging (communication barriers, limited opportunity for interaction,
      and physical environment). Pre- and posttest scores on the Multidisciplinary SWF
      Practice Learning Quiz, another instrument developed for this project,
      illustrated improvement in student understanding of other professions and the
      importance of interprofessional cooperation to promote and maintain healthy
      aging. Implications and suggestions for structuring learning opportunities that
      combine community health promotion practice and interprofessional learning are
      discussed.

PMID- 25621903
TI  - Harassment Due to Gender Nonconformity Mediates the Association Between Sexual
      Minority Identity and Depressive Symptoms.
AB  - The visibility of a stigmatized identity is central in determining how
      individuals experience that identity. Sexual minority status (e.g., identifying
      as gay, lesbian, or bisexual) has traditionally been identified as a concealable
      stigma, compared with race/ethnicity or physical disability status. This
      conceptualization fails to recognize, however, the strong link between sexual
      minority status and a visible stigma: gender nonconformity. Gender nonconformity,
      or the perception that an individual fails to conform to gendered norms of
      behavior and appearance, is strongly stigmatized, and is popularly associated
      with sexual minority status. The hypothesis that harassment due to gender
      nonconformity mediates the association between sexual minority status and
      depressive symptoms was tested. Heterosexual and sexual minority-identified
      college and university students (N = 251) completed questionnaires regarding
      their sexual minority identity, experiences of harassment due to gender
      nonconformity, harassment due to sexual minority status, and depressive symptoms.
      A mediational model was supported, in which the association between sexual
      minority identity and depressive symptoms occurred via harassment due to gender
      nonconformity. Findings highlight harassment due to gender nonconformity as a
      possible mechanism for exploring variability in depressive symptoms among sexual
      minorities.

PMID- 25621904
TI  - Structure-reactivity relationship of trifluoromethanesulfenates: discovery of an
      electrophilic trifluoromethylthiolating reagent.
AB  - A family of electrophilic trifluoromethanesulfenates was prepared. Structure
      reactivity relationship studies showed that the substituted groups on the aryl
      ring of the trifluoromethylthiolating reagent did not have an obvious influence
      on their reactivities. A simplified electrophilic trifluoromethylthiolating
      reagent 1c was then identified that can react with a wide range of nucleophiles
      such as Grignard reagents, arylboronic acids, alkynes, indoles, beta-ketoesters,
      oxindoles, and sodium sulfinates under mild reaction conditions. A variety of
      functional groups were tolerated under these conditions. 

PMID- 25621905
TI  - Quantification of variable functional-group densities of mixed-silane monolayers
      on surfaces via a dual-mode fluorescence and XPS label.
AB  - The preparation of aminated monolayers with a controlled density of functional
      groups on silica surfaces through a simple vapor deposition process employing
      different ratios of two suitable monoalkoxysilanes, (3
      aminopropyl)diisopropylethoxysilane (APDIPES) and (3
      cyanopropyl)dimethylmethoxysilane (CPDMMS), and advances in the reliable
      quantification of such tailored surfaces are presented here. The one-step
      codeposition process was carried out with binary silane mixtures, rendering
      possible the control over a wide range of densities in a single step. In
      particular, APDIPES constitutes the functional silane and CPDMMS the inert
      component. The procedure requires only small amounts of silanes, several ratios
      can be produced in a single batch, the deposition can be carried out within a few
      hours and a dry atmosphere can easily be employed, limiting self-condensation of
      the silanes. Characterization of the ratio of silanes actually bound to the
      surface can then be performed in a facile manner through contact angle
      measurements using the Cassie equation. The reliable estimation of the number of
      surface functional groups was approached with a dual-mode BODIPY-type
      fluorescence label, which allows quantification by fluorescence and XPS on one
      and the same sample. We found that fluorescence and XPS signals correlate over at
      least 1 order of magnitude, allowing for a direct linking of quantitative
      fluorescence analysis to XPS quantification. Employment of synchrotron-based
      methods (XPS; reference-free total reflection X-ray fluorescence, TXRF) made the
      traceable quantification of surface functional groups possible, providing an
      absolute reference for quantitative fluorescence measurements through a traceable
      measurement chain. 

PMID- 25621906
TI  - Association between cotinine-verified smoking status and metabolic syndrome:
      analyses of Korean National Health and Nutrition Examination Surveys 2008-2010.
AB  - BACKGROUND: The association between smoking and metabolic syndrome has not been
      clarified, especially for women, probably because of the inaccurate self-reported
      smoking status. This study aimed to investigate the association between cotinine
      verified smoking status and metabolic syndrome. METHODS: A total of 11,559
      participants from the Korean National Health and Nutrition Examination Surveys
      were included in this cross-sectional study. Metabolic syndrome was determined
      according to revised National Cholesterol Education Program Adult Treatment Panel
      III criteria. Smokers were distinguished from nonsmokers by a urinary cotinine
      level above 50 ng/mL. Multivariable adjusted logistic regression analysis was
      used to evaluate the association between cotinine-verified smoking status and
      metabolic syndrome. RESULTS: Prevalence of metabolic syndrome was 28.2% in men
      and 24.6% in women. Self-reported smoking status was much less consistent with
      cotinine-verified smoking status in women (kappa values=43.0%) compared with men
      (kappa value=88.6%). Risk of metabolic syndrome was significantly higher in
      cotinine-verified smokers than in nonsmokers for both men and women. Among the
      components of metabolic syndrome, smokers had an increased risk of high
      triglycerides (TGs), low high-density lipoprotein cholesterol, and decreased risk
      of high blood pressure compared with nonsmokers in men. In women, smokers had a
      higher risk of abdominal obesity and high TGs compared with nonsmokers.
      CONCLUSIONS: This population-based study showed that smoking was associated with
      increased risk for metabolic syndrome in men as well as in women and this
      association is mainly due to the association between smoking and dyslipidemia.

PMID- 25621907
TI  - Mega purchasing leads to a mega mess.

PMID- 25621909
TI  - Surgical training in Guyana: the next generation.
AB  - The pioneering surgical training partnership between the Canadian Association of
      General Surgeons (CAGS) and the University of Guyana has successfully graduated
      14 surgeons since 2006. The association has recruited 29 surgeons who have made
      75 teaching visits to Guyana, and CAGS involvement has been critical to providing
      local credibility to the program, organizing the curriculum structure and
      developing rigorous examinations. The program is now locally sustained, with
      graduates leading a number of clinical hospital programs. The initial diploma
      qualification is being reassessed, as other specialties have introduced
      postgraduate Master of Medicine degree programs. Many graduates are pursuing
      additional training opportunities overseas, and almost all of those remaining in
      Guyana have returned to the tertiary centre from the regional hospitals. The
      program has succeeded in training surgeons and raising the standards of surgical
      care in Guyana, but broader health system efforts are necessary to retain
      surgeons in outlying regional hospitals.

PMID- 25621910
TI  - The use of early immobilization in the management of acute soft-tissue injuries
      of the knee: results of a survey of emergency physicians, sports medicine
      physicians and orthopedic surgeons.
AB  - BACKGROUND: Evidence-based guidelines on the use of immobilization in the
      management of common acute soft-tissue knee injuries do not exist. Our objective
      was to explore the practice patterns of emergency physicians (EPs), sports
      medicine physicians (SMPs) and orthopedic surgeons (OS) regarding the use of
      early immobilization in the management of these injuries. METHODS: We developed a
      web-based survey and sent it to all EPs, SMPs and OS in a Canadian urban centre.
      The survey was designed to assess the likelihood of prescribing immobilization
      and to evaluate factors associated with physicians from these 3 disciplines
      making this decision. RESULTS: The overall response rate was 44 of 112 (39%): 17
      of 58 (29%) EPs, 7 of 15 (47%) SMPs and 20 of 39 (51%) OS. In cases of suspected
      meniscus injuries, 9 (50%) EPs indicated they would prescribe immobilization,
      whereas no SMPs and 1 (5%) OS would immobilize (p = 0.002). For suspected
      anterior cruciate ligament injuries, 13 (77%) EPs, 2 (29%) SMPs and 5 (25%) OS
      said they would immobilize (p = 0.005). For lateral collateral ligament injuries,
      9 (53%) EPs, no SMPs and 6 (32%) OS would immobilize (p = 0.04). All respondents
      would prescribe immobilization for a grossly unstable knee. CONCLUSION: We found
      that EPs were are more likely to prescribe immobilization for certain acute soft
      tissue knee injuries than SMPs and OS. The development of an evidenced- based
      guideline for the use of knee immobilization after acute soft-tissue injury may
      reduce practice variability.

PMID- 25621911
TI  - Do revision total hip augments provide appropriate modularity?
AB  - BACKGROUND: Porous metal acetabular augments have become widely used to fill bony
      defects in patients undergoing revision total hip arthroplasty. The objective of
      this study was to determine whether the currently offered size range of the
      augments is appropriate for surgical needs. METHODS: We reviewed the cases of all
      patients at 1 centre with a porous revision shell, and when an augment was used
      we recorded the patient and implant characteristics. RESULTS: We reviewed the
      cases of 281 patients, and augments were used in 24. Augment diameter was skewed
      toward the small end (p < 0.001), although thickness was not (p = 0.05); 21 of 24
      augments were those with the smallest 3 diameters and thicknesses. CONCLUSION:
      Given the sizes used, the full range of inventory provided by the manufacturer
      may be unnecessary, as surgeons will likely attempt a larger shell before a
      larger augment.

PMID- 25621912
TI  - Radiographic evaluation of the ankle syndesmosis.
AB  - BACKGROUND: Radiographic measurements to document ankle anatomy have been
      suggested in recent literature to be inadequate. Focus has been put on stress
      views and computed tomography; however, there are also issues with these
      modalities. An orthogonal view that could be used both statically and dynamically
      could help determine syndesmotic stability. The purpose of this study was to
      determine a parameter on a normal lateral ankle radiograph that will increase the
      reliability of standard radiography in diagnosing syndesmotic integrity. METHODS:
      Three orthopedic surgeons reviewed 80 lateral ankle radiographs. Thirty of those
      radiographs were reviewed on a second occasion. Rotation of the radiographs was
      determined by evaluating the overlap of the talar dome. Four radiographic
      parameters were measured 1 cm above the tibial plafond: fibular width, tibial
      width, and anterior and posterior tibiofibular intervals. RESULTS: Seventy-two
      radiographs were determined by consensus to be adequate. Means and ratios were
      documented to determine the relationship of the fibula to the tibia. Interrater
      reliability ranged from moderate to near-perfect, and the intrarater reliability
      was documented for each ratio. The anterior tibiofibular ratio was shown to be
      strong to near-perfect. It demonstrates that 40% of the tibia should be seen
      anterior to the fibula at 1cm above the tibial plafond. CONCLUSION: The anterior
      tibiofibular ratio provides an orthogonal measure for the syndesmosis that, in
      conjunction with those parameters previously documented, could clinically and
      economically improve the diagnosis of syndesmotic disruptions.

PMID- 25621914
TI  - Safety of a no-fast protocol for tracheotomy in critical care.

PMID- 25621913
TI  - Laparoscopic right hemicolectomy with intracorporeal versus extracorporeal
      anastamosis: a comparison of short-term outcomes.
AB  - BACKGROUND: There is wide variation among laparoscopic colon resection
      techniques, including the approach for mobilization and the extent of
      intracorporal vessel ligation, bowel division or anastamosis. We compared the
      short-term outcomes of laparoscopic right hemicolectomy (LRHC) with
      intracorporeal (IA) versus extracorporeal (EA) anastamosis. METHODS: We
      retrospectively reviewed all elective laparoscopic right hemicolectomies
      performed at St. Joseph's Hospital between January 2008 and September 2009 and
      compared the demographic, pathologic, operative and outcome data. RESULTS: Fifty
      LRHCs were completed during the study period: 21 IA and 29 EA. The groups were
      similar in age, sex, body mass index, American Society of Anesthesiologists
      score, previous laparotomy and preoperative invasive pathology. There was no
      difference between IA and EA in mean duration of surgery (170 v. 181 min, p =
      0.78), estimated blood loss (14 v. 42 mL, p = 0.15), perioperative blood
      transfusions (5% v. 14%, p = 0.29), in-hospital morbidity (33% v. 41%, p = 0.56),
      out-of-hospital morbidity (19% v. 31% p = 0.34), emergency department visits (10%
      v. 17%, p = 0.16) or 30-day readmissions (5% v. 7%, p = 0.75). There was 1
      anastamotic leak in each group and no perioperative deaths. Median length of stay
      was significantly shorter for IA (4 v. 5 d, p = 0.05). There were 6 extraction
      site hernias with EA and none with IA (p = 0.026). CONCLUSION: Laparoscopic right
      hemicolectomy with IA has the advantage of a less hernia-prone Pfannenstiel
      extraction site, faster recovery and shorter stay in hospital EA.

PMID- 25621915
TI  - The roles of experience, participation rates and judgment in the injury rates of
      weekend warriors.

PMID- 25621916
TI  - The roles of experience, participation rates and judgment in the injury rates of
      weekend warriors - Author's response.

PMID- 25621917
TI  - Humble correspondence: gaining a foothold in the surgical literature.

PMID- 25621918
TI  - Correction to Metallacarboranes as building blocks for polyanionic polyarmed aryl
      ether materials.

PMID- 25621919
TI  - A new zinc hydroxy acetate hydrogen carbonate lamellar phase for growing large
      and clean ZnO nanorod arrays.
AB  - A novel zinc hydroxy acetate hydrogen carbonate
      Zn5(OH)8.2(CH3COO)(HCO3)0.8.1.9H2O, isomorphous to Zn5(OH)8(CH3COO)2.xH2O, has
      been obtained by the reaction of zinc acetate dihydrate in aged ethylenediamine.
      This phase allows the growth of large arrays of oriented and crystallized
      nanorods up to 8 MUm in length on a substrate, without crystallization of
      additional particles. 

PMID- 25621920
TI  - Fear of negative evaluation, avoidance and mental distress among hearing-impaired
      employees.
AB  - OBJECTIVE: This study examined the relationship between hearing impairment and
      mental distress. We hypothesized that fear of negative evaluation by others and
      avoidant communication strategies are associated with increased symptoms of
      depression. METHOD: Hearing-impaired adults (N = 105) who signed up for a stress
      management course completed the Hospital Anxiety and Depression Scale (HAD;
      Zigmond & Snaith, 1983), the Fear of Negative Evaluation Scale (FNE; Watson &
      Friend, 1969), and the Conversation Tactics Checklist (CONV; Hallam et al.,
      2007). The participants' ratings of subjective hearing disability were assessed
      on a 5-point Likert scale and pure-tone audiometry obtained. Hierarchical
      multiple regression analysis was used to assess associations between fear of
      negative evaluation, avoidance, and symptoms of depression. RESULTS: OBJECTIVE
      hearing impairment was moderate or less for 81% (n = 87) of participants, and the
      correlation between subjective hearing disability and objective hearing
      impairment was not significant. Multiple regression analysis showed that fear of
      negative evaluation and avoidant communication strategies contributed
      significantly to the variance in depression symptoms, and the total explained
      variance was 41.7%, F(5, 93) = 13.32, p = .000. Subjective and objective hearing
      disability did not make significant contributions. CONCLUSION: Symptoms of
      depression appear to be closely related to fear of negative evaluation by others
      and use of avoidant communication strategies. Future clinical studies should
      address whether targeting these problems in rehabilitation interventions
      decreases depressive symptoms among hearing-impaired individuals.

PMID- 25621921
TI  - Understanding "on-water" catalysis of organic reactions. Effects of H+ and Li+
      ions in the aqueous phase and nonreacting competitor H-bond acceptors in the
      organic phase: on H2O versus on D2O for Huisgen cycloadditions.
AB  - For a typical Huisgen cycloaddition, carried out on water, the behavior of water
      molecules at the oil-water interface depended on the properties of the reactants.
      With weakly basic reactants, a small quantity of added H(+) (HClO4, 0.0001-0.01
      M) present in the aqueous phase had negligible effects, but larger quantities of
      H(+) (HClO4, 0.1-3.0 M) increased the catalytic effect and caused protons to
      cross the water-organic interface and affect the products. Added Li(+) ions
      (LiClO4, 0.1-3.0 M) had no effect for on-water reactions but enhanced the rates
      and endo products for in-water reactions. For these cycloaddition reactions, the
      product endo:exo ratios, when compared to those in organic solvents, can be used
      to distinguish between the on-water and in-water modes. Comparisons of organic
      reactions on H2O and on D2O indicate that on-water catalysis ranges from weak to
      strong trans-phase H-bonding for reactants with basic pK(a) < ca. -6 and to
      interfacial proton transfer for reactants with higher basic pK(a) > ca. 2 (pKa of
      conjugate acid). Water shows a chameleon-type response to organic molecules at
      hydrophobic surfaces.

PMID- 25621922
TI  - Transplanted Dentate Progenitor Cells Show Increased Survival in an Enriched
      Environment But Do Not Exert a Neurotrophic Effect on Spatial Memory Within 2
      Weeks of Engraftment.
AB  - Cyclin D2 knockout mice show decreased levels of endogenous dentate neurogenesis.
      We investigated whether transplanted dentate progenitor cells from wild-type mice
      respond in vivo to an enriched environment and whether they improve deficient
      dentate neurogenesis through a neurotrophic effect. Adult cyclin D2 knockout mice
      were transplanted with passaged adult progenitor cells and kept in an enriched
      environment or under standard housing conditions in isolation. After 1 week,
      animals living in an enriched environment underwent water maze testing.
      Progenitor cells grown on a laminin/poly-d-lysine monolayer expressed Sox2 and
      nestin and could be differentiated in vitro into neurons and astrocytes. After
      transplantation into the dentate gyrus, cells preferentially survived along the
      laminin-rich ependymal lining of the basal cistern or basal membrane of
      capillaries. A subpopulation of transplanted cells migrated into the interstitial
      space of the hippocampus and was not associated with laminin. Environmental
      enrichment led to a significant increase in the survival of transplanted
      progenitor cells on laminin in the dentate gyrus after 2 weeks. However, animals
      did not show an enhanced performance in the Morris water maze, and
      transplantation failed to exert a neurotrophic effect on endogenous neurogenesis
      after 2 weeks. However, a major limitation of the study is the short-term period
      of investigation, which may have been insufficient to capture functional effects.
      In conclusion, initial survival of transplanted neural progenitor cells was
      dependent on the presence of laminin and was significantly enhanced by
      environmental enrichment. Further studies are needed to address whether an
      enriched environment continues to promote graft survival over longer periods of
      time. 

PMID- 25621923
TI  - Testing likelihood ratios produced from complex DNA profiles.
AB  - The performance of any model used to analyse DNA profile evidence should be
      tested using simulation, large scale validation studies based on ground-truth
      cases, or alignment with trends predicted by theory. We investigate a number of
      diagnostics to assess the performance of the model using Hd true tests. Of
      particular focus in this work is the proportion of comparisons to non
      contributors that yield a likelihood ratio (LR) higher than or equal to the
      likelihood ratio of a known contributor (LRPOI), designated as p, and the average
      LR for Hd true tests. Theory predicts that p should always be less than or equal
      to 1/LRPOI and hence the observation of this in any particular case is of limited
      use. A better diagnostic is the average LR for Hd true which should be near to 1.
      We test the performance of a continuous interpretation model on nine DNA profiles
      of varying quality and complexity and verify the theoretical expectations.

PMID- 25621924
TI  - Developmental validation of a fully integrated sample-to-profile rapid human
      identification system for processing single-source reference buccal samples.
AB  - Short tandem repeat (STR) DNA typing is a global standard for human
      identification. Current practice involves highly trained forensic analysts,
      operating in a laboratory setting, using multiple instruments to process samples
      and analyze the data. Here, we report the developmental validation of a fully
      integrated and automated DNA profiling system, the RapidHIT(r) System, capable of
      producing up to five high quality STR profiles with full controls in
      approximately 90min using PowerPlex(r)16 HS RapidHIT chemistry. The system
      integrates all sample handling steps: starting from lysis of cells on buccal
      swabs or other buccal sample types through DNA extraction, normalization,
      amplification,capillary array electrophoresis, detection, and integrated software
      analysis. The results describe the developmental validation of the RapidHITTM
      System for buccal samples processed with the DNA IQTM extraction chemistry using
      a guandinium chaotropic agent and paramagnetic beads followed by amplification
      using a modified version of PowerPlex 16 HS chemistry (PowerPlex 16 HS RapidHIT
      chemistry), and capillary electrophoresis with manual review of genotyping data
      following interpretation guidelines. All processing from the buccal swab to
      generation and processing of the profile occurs on the RapidHIT platform. RESULT:
      are concordant with traditional methods, with 88% first pass success rates for
      both the CODIS and PowerPlex 16 loci. Average peak height ratios were 0.89 for
      buccal swabs. The system produces full profiles from swabs with at least 176 ng
      of saliva DNA. Rapid DNA identification systems will significantly enhance
      capabilities for forensic labs, intelligence, defense, law enforcement, refugee
      and immigration applications, and kinship analysis.

PMID- 25621925
TI  - Large phenyl-substituted acenes by cycloaddition reactions of the 2,6
      naphthodiyne synthon.
AB  - Phenyl-substituted tetra-, penta-, hexa- and octacenes were easily obtained
      starting from a readily available naphthalene-based bisaryne precursor. This
      approach to large acenes involves a sequence of two Diels-Alder cycloadditions
      with dienones followed by two CO extrusion reactions. 

PMID- 25621926
TI  - Medicaid use by documented and undocumented farm workers.
AB  - BACKGROUND: Despite considerable debate surrounding the use of Medicaid by
      undocumented immigrants, few studies address the extent of this use or estimate
      differences in the use between documented and undocumented households. METHOD: We
      analyzed data from the National Agricultural Workers Survey annual cross sections
      from 1993 through 2009, N = 41,342. Simple mean differences and logistic
      regressions predicted participation in Medicaid over 2-year intervals. RESULTS:
      Without adjustments for covariates, 12.2% of undocumented farm workers'
      households and 22.6% of documented households received Medicaid benefits,
      corresponding to an odds ratio of 0.48 (95% confidence interval, 0.33 to 0.69).
      By adding only covariates reflecting presence of children in the household, the
      odds ratio increased to 0.86 (95% confidence interval, 0.73 to 1.02).
      CONCLUSIONS: Undocumented farm workers' households were roughly half as likely to
      use Medicaid as documented households, and undocumented households' participation
      was especially responsive to the presence of children.

PMID- 25621927
TI  - A randomized clinical trial of family therapy in juvenile drug court.
AB  - The objective of this article is to examine the effectiveness of 2 theoretically
      different treatments delivered in juvenile drug court--family therapy represented
      by multidimensional family therapy (MDFT) and group-based treatment represented
      by adolescent group therapy (AGT)--on offending and substance use. Intent-to
      treat sample included 112 youth enrolled in juvenile drug court (primarily male
      [88%], and Hispanic [59%] or African American [35%]), average age 16.1 years,
      randomly assigned to either family therapy (n = 55) or group therapy (n = 57).
      Participants were assessed at baseline and 6, 12, 18 and 24 months following
      baseline. During the drug court phase, youth in both treatments showed
      significant reduction in delinquency (average d = .51), externalizing symptoms
      (average d = 2.32), rearrests (average d = 1.22), and substance use (average d =
      4.42). During the 24-month follow-up, family therapy evidenced greater
      maintenance of treatment gains than group-based treatment for externalizing
      symptoms (d = 0.39), commission of serious crimes (d = .38), and felony arrests
      (d = .96). There was no significant difference between the treatments with
      respect to substance use or misdemeanor arrests. The results suggest that family
      therapy enhances juvenile drug court outcomes beyond what can be achieved with a
      nonfamily based treatment, especially with respect to what is arguably the
      primary objective of juvenile drug courts: reducing criminal behavior and
      rearrests. More research is needed on the effectiveness of juvenile drug courts
      generally and on whether treatment type and family involvement influence
      outcomes. TRIAL REGISTRY NAME: Clinical Trials.gov, Identified NCT01668303.

PMID- 25621928
TI  - Using dynamic assessment to evaluate the expressive syntax of children who use
      augmentative and alternative communication.
AB  - The developmental readiness of four 5-year-old children to produce basic
      sentences using graphic symbols on an augmentative and alternative communication
      (AAC) device during a dynamic assessment (DA) task was examined. Additionally,
      the ability of the DA task to predict performance on a subsequent experimental
      task was evaluated. A graduated prompting framework was used during DA. Measures
      included amount of support required to produce the targets, modifiability (change
      in participant performance) within a DA session, and predictive validity of DA.
      Participants accurately produced target structures with varying amounts of
      support. Modifiability within DA sessions was evident for some participants, and
      partial support was provided for the measures of predictive validity. These
      initial results indicate that DA may be a viable way to measure young children's
      developmental readiness to learn how to sequence simple, rule-based messages via
      aided AAC.

PMID- 25621929
TI  - Effect of selective heparin desulfation on preservation of bone morphogenetic
      protein-2 bioactivity after thermal stress.
AB  - Bone morphogenetic protein-2 (BMP-2) plays an important role in bone and
      cartilage formation and is of interest in regenerative medicine. Heparin can
      interact electrostatically with BMP-2 and thus has been explored for controlled
      release and potential stabilization of this growth factor in vivo. However, in
      its natively sulfated state, heparin has potent anticoagulant properties that may
      limit its use. Desulfation reduces anticoagulant properties, but may impact
      heparin's ability to interact and protect BMP-2 from denaturation. The goal of
      this study was to characterize three selectively desulfated heparin species (N
      desulfated (Hep(-N)), 6-O,N-desulfated (Hep(-N,-6O)), and completely desulfated
      heparin (Hep(-))) and determine if the sulfation level of heparin affected the
      level of BMP-2 bioactivity after heat treatment at 65  degrees C. BMP-2
      bioactivity was evaluated using the established C2C12 cell assay. The resulting
      alkaline phosphatase activity data demonstrated that native heparin maintained a
      significant amount of BMP-2 bioactivity and the effect appeared to be heparin
      concentration dependent. Although all three had the same molecular charge as
      determined by zeta potential measurements, desulfated heparin derivatives Hep(-N)
      and Hep(-N,-6O) were not as effective as native heparin in maintaining BMP-2
      bioactivity (only ~35% of original activity remained in both cases). These
      findings can be used to better select desulfated heparin species that exhibit low
      anticoagulant activity while extending the half-life of BMP-2 in solution and in
      delivery systems.

PMID- 25621931
TI  - From cocaine to lidocaine: great progress with a tragic ending.

PMID- 25621930
TI  - PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models
      of hypertension.
AB  - OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is highly
      expressed in the kidney, where its function remains unclear. In vitro data
      suggested that PCSK9 could impair the trafficking of the epithelial Na channel
      (ENaC). Here, we aimed at determining the consequences of PCSK9-deficiency on
      blood pressure, sodium balance and ENaC function in vivo in mice. METHODS: Blood
      pressure was measured using non-invasive tail-cuff system or radiotelemetry under
      basal conditions in male and female PCSK9(+/+) and PCSK9(-/-) mice, as well as in
      models of hypertension: l-NAME (2 mg/kg/day), angiotensin II (1 mg/kg/day) and
      deoxycorticosterone acetate (DOCA)-salt in male mice only. Plasma and urine
      electrolytes (Na(+), K(+), Cl(-)) were collected under basal conditions, after
      DOCA-salt and amiloride treatment. Renal expression of ENaC subunits was assessed
      by western blotting. RESULTS: PCSK9-deficiency did not alter both basal blood
      pressure and its increase in salt-insensitive (l-NAME) and salt-sensitive (Ang-II
      and DOCA-salt) hypertension models. Plasma PCSK9 concentrations were increased by
      2.8 fold in DOCA-salt-induced hypertension. The relative expression of the
      cleaved, active, 30-kDa alphaENaC subunit was significantly increased by 32% in
      kidneys of PCSK9(-/-) mice under basal, but not under high-Na(+) diet or DOCA
      salt conditions. Amiloride increased urinary Na(+) excretion to similar level in
      both genotypes, indicating that ENaC activity was not affected by PCSK9
      deficiency. CONCLUSIONS: Despite an increase of cleaved alphaENaC under basal
      condition, PCSK9(-/-) mice display normal sodium balance and blood pressure
      regulation. Altogether, these data are reassuring regarding the development of
      PCSK9 inhibitors in hypercholesterolemia.

PMID- 25621932
TI  - Measuring the differential stoichiometry and energetics of ligand binding to
      macromolecules by single-molecule force spectroscopy: an extended theory.
AB  - Many chemical techniques exist for measuring the stoichiometry of ligand binding
      to a macromolecule; however, these techniques are often specific to certain
      ligands or require the presumption of specific binding models. Here, we further
      develop a previously reported, general, thermodynamic method for extracting the
      change in number of ligands bound to a macromolecule as that macromolecule
      undergoes a conformational transition driven by mechanical stretching, for
      example, by magnetic tweezers or optical trapping. We extend the theory of this
      method to consider systems with many ligands, experiments conducted in different
      thermodynamic ensembles (e.g., constant-force, constant-extension), and
      experiments in which the system is not at equilibrium. Further, we show that
      analysis of the same single-molecule mechanical manipulation data yields a
      measure of the differential free energy of stabilization due to ligand binding,
      that is, the free energy contribution by which ligand binding favors one
      conformation of the macromolecule over another. We interpret an existing data set
      measuring ion binding to RNA and DNA in terms of this free energy. 

PMID- 25621933
TI  - Biosynthesis of poly(3-hydroxypropionate) from glycerol using engineered
      Klebsiella pneumoniae strain without vitamin B12.
AB  - Poly(3-hydroxypropionate) (P3HP) is a biodegradable and biocompatible
      thermoplastic. Previous studies demonstrated that engineered Escherichia coli
      strains can produce P3HP with supplementation of expensive vitamin B12. The
      present study examined the production of P3HP from glycerol in the recombinant
      Klebsiella pneumoniae strain, which naturally synthesizes vitamin B12. The genes
      glycerol dehydratase and its reactivation factor (dhaB123, gdrA, and gdrB from K.
      pneumoniae), aldehyde dehydrogenase (aldH from E. coli) were cloned and expressed
      in K. pneumoniae to produce 3-hydroxypropionate (3HP), with 2 genes (dhaT and
      yqhD) for biosynthesis of 1,3-propanediol were deleted. To obtain P3HP
      production, propionyl-CoA synthetase (prpE from E. coli) and polyhydroxyalkanoate
      synthase (phaC from Ralstonia eutropha) were introduced. Under the appropriate
      aeration condition, the cell yield and P3HP content were 0.24 g/L and 12.7%
      (wt/wt [cell dry weight]) respectively along with 2.03 g/L 3HP after 48 h
      cultivation. Although the yield is relatively low, this study shows the
      feasibility of producing P3HP in K. pneumoniae from glycerol without vitamin B12
      for the first time. The results also suggest that the aeration conditions should
      be optimized carefully for the efficient production of P3HP. 

PMID- 25621934
TI  - The translational journey of brain beta-amyloid imaging: from positron emission
      tomography to autopsy to clinic.

PMID- 25621935
TI  - Copolyesters made from 1,4-butanediol, sebacic acid, and D-glucose by melt and
      enzymatic polycondensation.
AB  - Biotechnologically accessible 1,4-butanediol and vegetal oil-based diethyl
      sebacate were copolymerized with bicyclic acetalized D-glucose derivatives (Glux)
      by polycondensation both in the melt at high temperature and in solution at mild
      temperature mediated by polymer-supported Candida antarctica lipase B (CALB). Two
      series of random copolyesters (PB(x)Glux(y)Seb and PBSeb(x)Glux(y)) were prepared
      differing in which d-glucose derivative (Glux diol or Glux diester) was used as
      comonomer. The three parent homopolyesters PBSeb, PBGlux, and PGluxSeb were
      prepared as well. Both methods were found to be effective for polymerization
      although significant higher molecular weights were achieved by melt
      polycondensation. The thermal properties displayed by the copolyesters were
      largely dependent on composition and also on the functionality of the replacing
      Glux unit. The thermal stability of PBSeb was retained or even slightly increased
      after copolymerization with Glux, whereas crystallinity and melting temperature
      were largely depressed. On the contrary, the glass-transition temperature
      noticeably increased with the content in Glux units. PGluxSeb distinguished in
      displaying both T(g) and T(m) higher than PBSeb because a different crystal
      structure is adopted by this homopolyester. The hydrolytic degradability of PBSeb
      in water was enhanced by copolymerization, in particular, when biodegradation was
      assisted by lipases.

PMID- 25621936
TI  - Optical magnetism and plasmonic Fano resonances in metal-insulator-metal
      oligomers.
AB  - The possibility of achieving optical magnetism at visible frequencies using
      plasmonic nanostructures has recently been a subject of great interest. The
      concept is based on designing structures that support plasmon modes with electron
      oscillation patterns that imitate current loops, that is, magnetic dipoles.
      However, the magnetic resonances are typically spectrally narrow, thereby
      limiting their applicability in, for example, metamaterial designs. We show that
      a significantly broader magnetic response can be realized in plasmonic pentamers
      constructed from metal-insulator-metal (MIM) sandwich particles. Each MIM unit
      acts as a magnetic meta-atom and the optical magnetism is rendered quasi
      broadband through hybridization of the in-plane modes. We demonstrate that
      scattering spectra of individual MIM pentamers exhibit multiple Fano resonances
      and a broad subradiant spectral window that signals the magnetic interaction and
      a hierarchy of coupling effects in these intricate three-dimensional nanoparticle
      oligomers. 

PMID- 25621937
TI  - Undifferentiated pulp cells and odontoblast-like cells share genes involved in
      the process of odontogenesis.
AB  - OBJECTIVE: Expression of a large number of genes during differentiation of
      undifferentiated pulp cells into odontoblastic cells is still unknown, hence the
      aim of this investigation was to compare undifferentiated pulp cells (OD-21) and
      odontoblast-like cells (MDPC-23) through the assessment of cell stimulation and
      gene expression profiling. DESIGN: The cells were cultured and after the
      experimental periods, there were evaluated cell proliferation and viability as
      well as alkaline phosphatase activity (ALP) and mineralization nodules. To
      evaluate gene expression it was used fluorescence cDNA microarray technology in
      addition to bioinformatics programmes such as SAM (significance analysis of
      microarrays). Gene expression was validated by Real Time PCR (qPCR). RESULTS: The
      results showed that viability was above 80% in both cells, cell proliferation and
      ALP activity was higher in MDPC-23 cells and mineralization nodules were present
      only in the cultures of odontoblast-like cells. There were observed genes
      associated to odontogenesis with similar behaviour in both cell types, such as
      Il10, Traf6, Lef1 and Hspa8. Regions of the heatmap showed differences in
      induction and repression of genes such as Jak2 and Fas. CONCLUSION: OD-21 cells
      share many genes with similar behaviour to MDPC-23 cells, suggesting their
      potential to differentiate into odontoblasts.

PMID- 25621938
TI  - Antioxidants and biomarkers of oxidative damage in the saliva of patients with
      Down's syndrome.
AB  - BACKGROUND: The aim of this study was to investigate enzymatic and non-enzymatic
      antioxidant systems and levels of biomarker levels of oxidative damage in the
      saliva of patients with Down's syndrome (DS). METHODS: Saliva samples were
      collected from 30 patients with DS and control group (age: 14-24 years).
      Subsequently, the concentrations of superoxide dismutase, concentration of
      malondialdehyde, carbonylated proteins, uric acid, vitamin C and total protein,
      peroxidase activity and total antioxidant capacity were analyzed. RESULTS:
      Patients with DS presented significantly higher concentrations of superoxide
      dismutase, higher levels of malondialdehyde and salivary total protein content
      than controls (p<0.05). Conversely, no difference in carbonylated proteins or
      antioxidants (uric acid, vitamin C, peroxidase, and total antioxidant capacity)
      was observed between DS patients and controls (p>0.05). CONCLUSION: Patients with
      DS are more vulnerable to oxidative stress in saliva as indicated by the
      significant increase in malondialdehyde and superoxide dismutase concentrations
      found in this study.

PMID- 25621939
TI  - Micro-computed tomography and histomorphometric analysis of the effects of
      platelet-rich fibrin on bone regeneration in the rabbit calvarium.
AB  - OBJECTIVE: The present study aimed to investigate the effectiveness of platelet
      rich fibrin (PRF) on bone regeneration when used alone or in combination with
      hydroxyapatite (HA)/beta-tricalcium phosphate (betaTCP). DESIGN: In this study,
      20 New Zealand white rabbits were used and four calvarial defects were prepared
      in each animal. PRF, Straumann((r)) Bone Ceramic (SBC), or PRF+SBC was applied to
      the defects; one defect was left untreated as a control. Ten rabbits were
      sacrificed at week 4 (T1) and 10 at week 8 (T2). After micro-computed tomography
      (micro-CT) scanning, the samples were sent for histological and histomorphometric
      analysis to evaluate and compare the volume and area of regenerated bone.
      RESULTS: Histomorphometric and micro-CT analysis showed that both PRF and SBC
      significantly increased bone regeneration at T1 and T2 (P<0.01). When PRF was
      used in combination with HA/betaTCP, a further significant increase in new bone
      formation was observed at T1 and T2 compared with that when PRF or SBC was used
      alone (P<0.01). CONCLUSIONS: PRF has a positive effect on bone formation when
      used alone and in combination with HA/betaTCP.

PMID- 25621940
TI  - Loss of heat acclimation and time to re-establish acclimation.
AB  - Acclimation in a hot environment is one potent means to decrease the heat strain
      of work in a hot environment. However, with diminished heat exposure, positive
      adaptations of acclimation may be lost. This rate of loss is equivocal and, once
      established, could be used to prescribe the time for re-acclimation. The purpose
      of this study was to determine the rate of loss of heat acclimation over a period
      of 6 weeks and determine the time needed for re-acclimation after 2 weeks and 4
      weeks of de-acclimation in ten healthy participants. All participants first
      underwent an initial acclimation period (a 3-day plateau in Tre was used to
      signify acclimation). Based on the mean time to acclimate in Phase 1 (mean time
      to acclimate = 6.1 +/- 1.4 days), the loss of acclimation was mapped and
      participants were randomly assigned to one of two groups: one that underwent one
      2-hr heat exposure at 1, 3, and 5 weeks post-acclimation, and one that underwent
      one 2-hr heat exposure session at 2,4, and 6 weeks. Complete loss of acclimation
      occurred in 6 weeks and, as expected, work HR and Tre increased with increasing
      time away from the heat (p<0.05). Based on the time for total loss of acclimation
      from Phase 1, participants in Phase 2 (n = 8) first underwent acclimation. Then,
      after either a 2-week or 4-week absence from the heat, participants returned to
      the laboratory for re-acclimation. While not statistically significant yet
      practically significant (p = 0.18; one-tailed confidence interval), average days
      for re-acclimation in the 2-week group tended to be fewer than in the 4-week
      group (days for re-acclimation = 3.8 +/- 1.2 and 5.3 +/- 1.9, respectively).
      Based on these general trends, for occupational settings, a re-acclimation period
      of 4 days is recommended after 2 weeks absence from the heat, 5 days for 4 weeks
      absence from the heat, and complete acclimation (6 days) after 6 weeks absence or
      more from the heat.

PMID- 25621941
TI  - Brooktrout Lake case study: biotic recovery from acid deposition 20 years after
      the 1990 Clean Air Act Amendments.
AB  - The Adirondack Mountain region is an extensive geographic area (26,305 km(2)) in
      upstate New York where acid deposition has negatively affected water resources
      for decades and caused the extirpation of local fish populations. The water
      quality decline and loss of an established brook trout (Salvelinus fontinalis
      [Mitchill]) population in Brooktrout Lake were reconstructed from historical
      information dating back to the late 1880s. Water quality and biotic recovery were
      documented in Brooktrout Lake in response to reductions of S deposition during
      the 1980s, 1990s, and 2000s and provided a unique scientific opportunity to re
      introduce fish in 2005 and examine their critical role in the recovery of food
      webs affected by acid deposition. Using C and N isotope analysis of fish collagen
      and state hatchery feed as well as Bayesian assignment tests of microsatellite
      genotypes, we document in situ brook trout reproduction, which is the initial
      phase in the restoration of a preacidification food web structure in Brooktrout
      Lake. Combined with sulfur dioxide emissions reductions promulgated by the 1990
      Clean Air Act Amendments, our results suggest that other acid-affected Adirondack
      waters could benefit from careful fish re-introduction protocols to initiate the
      ecosystem reconstruction of important components of food web dimensionality and
      functionality. 

PMID- 25621942
TI  - Enhanced solubility and targeted delivery of curcumin by lipopeptide micelles.
AB  - A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid
      (C12) as the hydrophobic tails has been designed and prepared by standard solid
      phase peptide synthesis technique. LP can self-assemble into spherical micelles
      with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin
      loaded LP micelles were prepared in order to increase the water solubility,
      sustain the releasing rate, and improve the tumor targeted delivery of curcumin.
      Water solubility, cytotoxicity, in vitro release behavior, and intracellular
      uptake of curcumin-loaded LP micelles were investigated. The results showed that
      LP micelles can increase the water solubility of curcumin 1.1 * 10(3) times and
      sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed
      much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa)
      and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and
      COS7 cells, due to the over-expression of integrins on cancer cells, the micelles
      can efficiently use the tumor-targeting function of RGD (functionalized peptide
      sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better
      efficiency of the self-assembled LP micelles for curcumin delivery than crude
      curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays.
      Combined with the enhanced solubility and higher cell inhibition, LP micelles
      reported in this study may be promising in clinical application for targeted
      curcumin delivery. 

PMID- 25621943
TI  - Microperimetric assessment of retinal sensitivity in eyes with diabetic macular
      edema from a phase 2 study of intravitreal aflibercept.
AB  - PURPOSE: To evaluate retinal sensitivity in patients with diabetic macular edema
      who received intravitreal aflibercept injection (IAI) or laser. METHODS: A
      substudy included 46 patients from DA VINCI (a randomized, double-masked Phase 2
      study) receiving either laser, 0.5 mg IAI every 4 weeks, 2 mg IAI every 4 weeks,
      2 mg IAI every 8 weeks after 3 monthly doses (2q8), or 2 mg IAI as-needed after 3
      monthly doses for 52 weeks. Retinal sensitivity was measured in one (central),
      five (one central and four inner), and eight (four inner and four outer) optical
      coherence tomography subfields. RESULTS: Mean best-corrected visual acuity
      improvement in the subgroup at Week 52 was 3.3 letters with laser and ranged from
      5.4 to 16.3 letters in the IAI groups. Retinal sensitivity of laser patients at
      Week 52 was comparable with baseline in the central optical coherence tomography
      subfield but decreased in the five and eight optical coherence tomography
      subfields. Compared with laser, retinal sensitivity significantly increased with
      IAI in the 2q8 and pooled IAI groups in the 5 and 8 optical coherence tomography
      subfields at Week 52 (P < 0.05). CONCLUSION: Intravitreal aflibercept injection
      improved best-corrected visual acuity and retinal sensitivity in this subgroup of
      patients. Laser may cause a deterioration of macular function that is not
      detectable with best-corrected visual acuity testing.

PMID- 25621944
TI  - Case-matched comparison of vitrectomy, peripheral retinal endolaser, and
      endocyclophotocoagulation versus standard care in neovascular glaucoma.
AB  - PURPOSE: To evaluate the efficacy of combination pars plana vitrectomy,
      endoscopic peripheral panretinal photocoagulation, and endocyclophotocoagulation
      (ECP) as compared with standard care in patients with neovascular glaucoma.
      METHODS: This age-matched case-controlled retrospective series of 54 eyes
      compared the clinical outcomes between a consecutive series of combination pars
      plana vitrectomy/panretinal photocoagulation/ECP (n = 27) versus the current
      standard of care (n = 27) for patients with neovascular glaucoma. "Standard"
      treatments for patients with neovascular glaucoma include panretinal
      photocoagulation, intravitreal bevacizumab, filtration surgery, pars plana
      vitrectomy, and Ahmed valve placement. RESULTS: After 1 year, mean intraocular
      pressure reduced from 40.7 +/- 12.40 mmHg preoperatively to 12.3 +/- 4.84 mmHg (P
      < 0.001) in the ECP group and from 34.7 +/- 12.38 mmHg to 23.2 +/- 12.34 mmHg in
      the control group (P = 0.002). Compared with controls, the mean drop in
      intraocular pressure in the ECP group was significantly greater at all
      postoperative visits. Logarithm of the minimal angle of resolution visual acuity
      outcomes were similar in both groups. There were 2 cases (7.4%) of postoperative
      phthisis bulbi in each group. CONCLUSION: Endoscopic pars plana vitrectomy,
      panretinal photocoagulation, and ECP seem to control intraocular pressure to a
      greater extent than standard glaucoma treatments in patients with neovascular
      glaucoma. In this aged-matched comparative case series, there was no significant
      difference between the two treatments' effects on visual acuity.

PMID- 25621945
TI  - Comparison of attraction capabilities associated with high-speed, dual-pneumatic
      vitrectomy probes.
AB  - PURPOSE: To measure membrane attraction capabilities of enhanced 27-gauge,
      enhanced 25-gauge, and 23-gauge vitrectomy probes under various parameters.
      METHODS: A membrane-on-cantilever apparatus was used to measure membrane
      attraction for enhanced 27-, enhanced 25-, and 23-gauge UltraVit probes (n = 6
      for each). The following parameters were evaluated: effects of cut rates and duty
      cycles on membrane attraction distances, and flow rates and vacuum levels
      required to attract a membrane at a fixed distance. RESULTS: The enhanced 27
      gauge probe had the shortest attraction distance across all cutting speeds and
      duty cycles. To attract a membrane at a fixed distance, increasing vacuum was
      necessary with higher cutting rates and smaller probe gauges but flow rate
      remained relatively constant. The biased open duty cycle was associated with a
      longer attraction distance than 50/50 or biased closed modes. CONCLUSION: The
      shorter membrane attraction distance of the enhanced 27-gauge probe versus 23
      gauge and enhanced 25-gauge probes may permit greater membrane dissection
      precision while providing improved access to small tissue planes. Equivalent
      fluid flow capabilities of the 27-gauge probe compared with the 23-gauge and 25
      gauge probes may provide efficient aspiration. Surgeon selection of duty cycle
      modes may improve intraoperative fluid control and expand the cutter utility as a
      multifunctional tool.

PMID- 25621946
TI  - Moment of cyst eruption captured by optical coherence tomography in diabetic
      macular edema.

PMID- 25621947
TI  - Cells at the vitreoretinal interface in small full-thickness macular holes.
AB  - PURPOSE: To report on total number, distribution, and type of cells at the
      vitreomacular interface in small full-thickness macular holes. METHODS: Internal
      limiting membrane specimens were removed from 20 consecutive patients with
      macular holes <250 MUm at times when pharmacologic vitreolysis was not available.
      Specimens were flat mounted and investigated by phase contrast and interference
      microscopy and immunocytochemistry. Clinical data were documented including
      optical coherence tomography analysis using the caliper function. Thirteen
      antibodies were used for glial cells, hyalocytes, macrophages, retinal pigment
      epithelial cells, different types of collagen, alpha-smooth muscle actin, and
      proliferating cells. RESULTS: There was a positive correlation between macular
      hole size and cell density at the internal limiting membrane (Spearman's Rho: r =
      0.519, P = 0.019). Mostly, single glial cells were found on the internal limiting
      membrane. In five patients, cell clusters were present. There was a strong
      immunoreactivity for glial cell markers. Immunoreactivity of hyalocyte markers,
      alpha-smooth muscle actin, and Ki-67 was found in cell clusters but otherwise
      sparse. CONCLUSION: Single cells of glial origin without signs of proliferation
      or contraction are present in eyes with small full-thickness macular holes. In
      some eyes, however, clusters of cells can be seen, capable of proliferation and
      exerting tangential traction. Our findings emphasize the need for better
      visualization of the vitreoretinal pathology by optical coherence tomography,
      especially to distinguish between single cells and cell clusters.

PMID- 25621948
TI  - How has high-resolution multimodal imaging refined our understanding of the
      vasogenic process in type 3 neovascularization?

PMID- 25621949
TI  - Myosin II controls cellular branching morphogenesis and migration in three
      dimensions by minimizing cell-surface curvature.
AB  - In many cases, cell function is intimately linked to cell shape control. We used
      endothelial cell branching morphogenesis as a model to understand the role of
      myosin II in shape control of invasive cells migrating in 3D collagen gels. We
      applied principles of differential geometry and mathematical morphology to 3D
      image sets to parameterize cell branch structure and local cell-surface
      curvature. We find that Rho/ROCK-stimulated myosin II contractility minimizes
      cell-scale branching by recognizing and minimizing local cell-surface curvature.
      Using microfabrication to constrain cell shape identifies a positive feedback
      mechanism in which low curvature stabilizes myosin II cortical association, where
      it acts to maintain minimal curvature. The feedback between regulation of myosin
      II by curvature and control of curvature by myosin II drives cycles of localized
      cortical myosin II assembly and disassembly. These cycles in turn mediate
      alternating phases of directionally biased branch initiation and retraction to
      guide 3D cell migration.

PMID- 25621950
TI  - Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic
      niche to promote metastasis.
AB  - Reprogrammed glucose metabolism as a result of increased glycolysis and glucose
      uptake is a hallmark of cancer. Here we show that cancer cells can suppress
      glucose uptake by non-tumour cells in the premetastatic niche, by secreting
      vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in
      the circulation have been associated with metastasis in breast cancer patients,
      and we show that cancer-cell-secreted miR-122 facilitates metastasis by
      increasing nutrient availability in the premetastatic niche. Mechanistically,
      cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and
      in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo
      inhibition of miR-122 restores glucose uptake in distant organs, including brain
      and lungs, and decreases the incidence of metastasis. These results demonstrate
      that, by modifying glucose utilization by recipient premetastatic niche cells,
      cancer-derived extracellular miR-122 is able to reprogram systemic energy
      metabolism to facilitate disease progression.

PMID- 25621951
TI  - USP30 and parkin homeostatically regulate atypical ubiquitin chains on
      mitochondria.
AB  - Multiple lines of evidence indicate that mitochondrial dysfunction is central to
      Parkinson's disease. Here we investigate the mechanism by which parkin, an E3
      ubiquitin ligase, and USP30, a mitochondrion-localized deubiquitylase, regulate
      mitophagy. We find that mitochondrial damage stimulates parkin to assemble Lys 6,
      Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific
      deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked
      multimers. Using mass spectrometry, we show that recombinant USP30 preferentially
      removes these linkage types from intact ubiquitylated mitochondria and
      counteracts parkin-mediated ubiquitin chain formation in cells. These results,
      combined with a series of chimaera and localization studies, afford insights into
      the mechanism by which a balance of ubiquitylation and deubiquitylation regulates
      mitochondrial homeostasis, and suggest a general mechanism for organelle
      autophagy.

PMID- 25621952
TI  - Platelet-derived SDF-1 primes the pulmonary capillary vascular niche to drive
      lung alveolar regeneration.
AB  - The lung alveoli regenerate after surgical removal of the left lobe by
      pneumonectomy (PNX). How this alveolar regrowth/regeneration is initiated remains
      unknown. We found that platelets trigger lung regeneration by supplying stromal
      cell-derived factor-1 (SDF-1, also known as CXCL12). After PNX, activated
      platelets stimulate SDF-1 receptors CXCR4 and CXCR7 on pulmonary capillary
      endothelial cells (PCECs) to deploy the angiocrine membrane-type
      metalloproteinase MMP14, stimulating alveolar epithelial cell (AEC) expansion and
      neo-alveolarization. In mice lacking platelets or platelet Sdf1, PNX-induced
      alveologenesis was diminished. Reciprocally, infusion of Sdf1(+/+) but not Sdf1
      deficient platelets rescued lung regeneration in platelet-depleted mice.
      Endothelial-specific ablation of Cxcr4 and Cxcr7 in adult mice similarly impeded
      lung regeneration. Notably, mice with endothelial-specific Mmp14 deletion
      exhibited impaired expansion of AECs but not PCECs after PNX, which was not
      rescued by platelet infusion. Therefore, platelets prime PCECs to initiate lung
      regeneration, extending beyond their haemostatic contribution. Therapeutic
      targeting of this haemo-vascular niche could enable regenerative therapy for lung
      diseases.

PMID- 25621953
TI  - Cdk1-dependent mitotic enrichment of cortical myosin II promotes cell rounding
      against confinement.
AB  - Actomyosin-dependent mitotic rounding occurs in both cell culture and tissue,
      where it is involved in cell positioning and epithelial organization. How
      actomyosin is regulated to mediate mitotic rounding is not well understood. Here
      we characterize the mechanics of single mitotic cells while imaging actomyosin
      recruitment to the cell cortex. At mitotic onset, the assembly of a uniform
      DIAPH1-dependent F-actin cortex coincides with initial rounding. Thereafter,
      cortical enrichment of F-actin remains stable while myosin II progressively
      accumulates at the cortex, and the amount of myosin at the cortex correlates with
      intracellular pressure. Whereas F-actin provides only short-term (<10 s)
      resistance to mechanical deformation, myosin sustains intracellular pressure for
      a longer duration (>60 s). Our data suggest that progressive accumulation of
      myosin II to the mitotic cell cortex probably requires the Cdk1 activation of
      both p21-activated kinases, which inhibit myosin recruitment, and of Rho kinase,
      which stimulates myosin recruitment to the cortex.

PMID- 25621954
TI  - [Motor replacement surgery via tendon transfer in radial nerve palsy].
AB  - OBJECTIVE: Restoration of active extension of wrist, thumb and digits by muscle
      tendon transposition. INDICATIONS: Radial nerve palsy due to peripheral nerve
      injury. Peripheral nerve disease. Muscle or tendon injury. Restoration of wrist
      extension in high radial nerve palsy. CONTRAINDICATIONS: Reversible distal radial
      nerve palsy, absence of suitable donor muscles, spasticity, limited range of
      motion of affected joints, extensive scarring and inappropriate soft tissue
      conditions, unjustifiable loss of function at donor site. Reinnervated donor
      muscles, progressive muscle disease, insufficient patient compliance. SURGICAL
      TECHNIQUE: Dissection of the flexor carpi ulnaris, palmaris longus and pronator
      teres tendon insertion. Transposition of the tendons. Interweaving of tendons of
      the pronator teres and extensor carpi radialis brevis muscles, the extensor
      digitorum communis and flexor carpi ulnaris muscles, as well as the extensor
      pollicis longus and palmaris longus muscles using the Pulvertaft technique.
      POSTOPERATIVE MANAGEMENT: 3 Weeks immobilization in forearm splint. Additional
      immobilization for 2 weeks at night. Subsequently, intensive physical and
      occupational therapy for another 4-6 weeks is required, starting 3 weeks
      postoperatively. RESULTS: The procedure was carried out in 12 patients over the
      past 14 years. We treated proximal radial nerve palsy in nine cases. In
      accordance with the current medical literature, we consider the described motor
      replacement surgery a reliable procedure.

PMID- 25621955
TI  - [Periprosthetic defects of the knee].

PMID- 25621957
TI  - Good patient communication: More than "Say aahhh".

PMID- 25621958
TI  - The critical role of physician assistants in caring for patients with asthma.

PMID- 25621959
TI  - Diagnosing oral ulcers.
AB  - Oral ulcers are common and can have many causes, making diagnosis challenging.
      This article provides an overview of common oral ulcers and an algorithmic
      approach to establishing the correct diagnosis. Factors such as duration, pattern
      of recurrence, clinical appearance, mucosal location, and presence or absence of
      systemic symptoms are useful clues to determining an ulcer's cause. 

PMID- 25621960
TI  - On PA autonomy.

PMID- 25621961
TI  - What is the role of sofosbuvir in treating hepatitis C infection?
AB  - Sofosbuvir, a nucleotide polymerase inhibitor, was approved in 2013 for treating
      hepatitis C infection in adults. This article reviews the use of sofosbuvir in
      combination with ribavirin with or without pegylated interferon. 

PMID- 25621963
TI  - Abdominal adenopathy found during a routine follow-up.
AB  - During routine follow-up of a 60-year-old man with an endoluminal lesion of the
      duodenum, we found a persistent reactive abdominal adenopathy of unknown origin,
      later diagnosed as an abdominal localization of sarcoidosis. This article focuses
      on the differential diagnosis of abdominal granulomatous lymphadenopathies, the
      management of abdominal adenopathy of unknown origin, and the difficult decision
      making about sampling lymph nodes with reactive and inflammatory echographic
      appearance. 

PMID- 25621964
TI  - Transcatheter aortic valve replacement: When invasive surgery is not an option.
AB  - Aortic stenosis is a common problem that typically results from calcification and
      degenerative changes of the aortic valve that occur with advancing age. Because
      medical therapies have no clinically proven role, the management of severe aortic
      stenosis has primarily been surgical. For patients who are too high-risk for
      surgical aortic valve repair, transcatheter aortic valve repair (TAVR), approved
      by the FDA in 2011, may be an option. This article outlines what clinicians need
      to know about TAVR. 

PMID- 25621965
TI  - Anorexia nervosa.

PMID- 25621966
TI  - A chronic foot ulcer and a swollen, painful leg.

PMID- 25621967
TI  - Patient blood management to reduce transfusion need.
AB  - Patient blood management is a multidisciplinary, patient-centered approach aimed
      at improving patient outcomes, preserving the blood supply, and reducing costs.
      By identifying patients at risk for transfusion and taking steps to maintain
      hemoglobin concentration, manage anemia, optimize hemostasis, and minimize blood
      loss, clinicians can improve patient outcomes. 

PMID- 25621968
TI  - Post-trauma implications of a complex Gustilo type 3B fracture.

PMID- 25621969
TI  - When the art of medicine becomes business as usual.

PMID- 25621970
TI  - 6-shogaol, an active constituent of dietary ginger, impairs cancer development
      and lung metastasis by inhibiting the secretion of CC-chemokine ligand 2 (CCL2)
      in tumor-associated dendritic cells.
AB  - This study has two novel findings: it is not only the first to demonstrate that
      tumor-associated dendritic cells (TADCs) facilitate lung and breast cancer
      metastasis in vitro and in vivo by secreting inflammatory mediator CC-chemokine
      ligand 2 (CCL2), but it is also the first to reveal that 6-shogaol can decrease
      cancer development and progression by inhibiting the production of TADC-derived
      CCL2. Human lung cancer A549 and breast cancer MDA-MB-231 cells increase TADCs to
      express high levels of CCL2, which increase cancer stem cell features, migration,
      and invasion, as well as immunosuppressive tumor-associated macrophage
      infiltration. 6-Shogaol decreases cancer-induced up-regulation of CCL2 in TADCs,
      preventing the enhancing effects of TADCs on tumorigenesis and metastatic
      properties in A549 and MDA-MB-231 cells. A549 and MDA-MB-231 cells enhance CCL2
      expression by increasing the phosphorylation of signal transducer and activator
      of transcription 3 (STAT3), and the activation of STAT3 induced by A549 and MDA
      MB-231 is completely inhibited by 6-shogaol. 6-Shogaol also decreases the
      metastasis of lung and breast cancers in mice. 6-Shogaol exerts significant
      anticancer effects on lung and breast cells in vitro and in vivo by targeting the
      CCL2 secreted by TADCs. Thus, 6-shogaol may have the potential of being an
      efficacious immunotherapeutic agent for cancers. 

PMID- 25621971
TI  - Stress testing in the emergency department: not which test but whether any test
      should be done.

PMID- 25621972
TI  - Demographics of clinical trials participants in pivotal clinical trials for new
      molecular entity drugs and biologics approved by FDA From 2010 to 2012.
AB  - To fully assess the safety and efficacy of therapeutics before approval, the US
      Food and Drug Administration (FDA) has encouraged adequate representation and
      assessment of demographic subgroups in clinical trials through guidance documents
      and regulations. This study aimed to survey the demographics of participants in
      pivotal clinical trials, as well as the presence of analyses by sex on efficacy
      and safety for FDA-approved new drug applications (NDAs) and biologics license
      applications (BLAs) from 2010 to 2012. Medical and statistical reviews for new
      molecular entity drugs and biological products approved during this period were
      obtained from Drugs@FDA. All pivotal clinical trials referenced in the FDA
      reviews were evaluated for the participation of different demographic subgroups
      (such as sex, race/ethnicity, and age). Pivotal trials were defined as those
      phase 2 and/or phase 3 trials described in the labeling or the FDA medical
      reviews in support of the drug/biological approval. Eighty-three new molecular
      entities (66 NDAs and 17 BLAs) were approved by the FDA from 2010 to 2012.
      Overall, women constituted 45% of trial participants for NDAs and 65% for BLAs.
      Sex analysis related to safety and efficacy was reported in 92% of the surveyed
      FDA medical and statistical reviews. Most NDAs and BLAs (82%) had a study
      population that was representative of the sex distribution for the intended
      patient population; however, most study participants were whites (77%), and
      minority racial/ethnic groups had lower participation rates in the study
      population than would be representative of the US racial group populations. 

PMID- 25621973
TI  - New Hydrophobic IOL Materials and Understanding the Science of Glistenings.
AB  - An introduction to the history of intraocular lenses (IOLs) is given, leading up
      to modern hydrophobic examples. The roles of hydrophobicity, hygroscopy,
      materials chemistry, and edge design are discussed in the context of IOLs. The
      four major types of IOL materials are compared in terms of their chemistry and
      biocompatibility. An example of a modern "hydrophobic" acrylic polymer with
      higher water content is discussed in detail. 

PMID- 25621974
TI  - No evidence for association of autism with rare heterozygous point mutations in
      Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated
      Proteins or Contactins.
AB  - Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein
      Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based
      on findings from homozygosity mapping, molecular cytogenetics, copy number
      variation analyses, and both common and rare single nucleotide association
      studies. However, data specifically with regard to the contribution of
      heterozygous single nucleotide variants (SNVs) have been inconsistent. In an
      effort to clarify the role of rare point mutations in CNTNAP2 and related gene
      families, we have conducted targeted next-generation sequencing and evaluated
      existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find
      no evidence for statistically significant association of rare heterozygous
      mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked
      limits on the scale of their plausible contribution to risk. 

PMID- 25621975
TI  - The response of hepatitis B vaccination on seronegative adults with different
      vaccination schedules.
AB  - The purpose of this study was to compare the response of hepatitis B vaccination
      with different vaccination schedules among seronegative adults, and to provide
      suitable vaccination schedules for floating and fixed population. The study
      included adults aged 20 to 39 y without prior history of vaccination with
      hepatitis B vaccine. The serum samples were collected and tested for hepatitis B
      surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B
      core antibody (anti-HBc) levels. Out of all, 686 adults who were negative for
      anti-HBs, anti-HBc and HBsAg were vaccinated with 10 ug hepatitis B vaccine at 0,
      1 and 3, 6 or 12 month schedules, and their antibody titers were monitored. The
      rates of completion of the vaccination in floating and fixed population were
      90.4% and 94.1% respectively (p = 0.061). The anti-HBs positive rates in adults
      vaccinated at 0, 1 and 3 ,6 or 12 month were 83.9%, 88.2% and 94.2% respectively
      (P = 0.0003). The corresponding geometric mean titers (GMTs) were 61.19
      (95%CI:47.10-81.23) mIU/mL, 214.04(95%CI:157.14-291.61) mIU/mL and
      345.78(95%CI:251.25-475.77) mIU/mL, respectively ( P < 0.0001). Vaccination of
      hepatitis B with both 0-1-6 and 0-1-12 month schedules in adults result in better
      level of immune responses. Also, a longer vaccination schedule (0-1-12 month) may
      be more suitable for floating population and 0-1-6 month schedule is recommended
      for the fixed population.

PMID- 25621977
TI  - An insight into the role of oxygen vacancy in hydrogenated TiO2 nanocrystals in
      the performance of dye-sensitized solar cells.
AB  - Hydrogenated titanium dioxide (H-TiO2) nanocrystals were successfully prepared
      via annealing TiO2 in H2/N2 mixed gas flow at elevated temperatures ranging from
      300 to 600  degrees C. Electron paramagnetic resonance (EPR) spectra were used to
      determine the produced oxygen vacancy in H-TiO2. Variations in temperature were
      studied to investigate the concentration change of oxygen vacancy in H-TiO2. The
      H-TiO2 nanocrystals prepared at different temperatures were employed into
      photoanodes sensitized by N719 dye and found to have exceptional effect on the
      solar-to-electric energy conversion efficiency (eta). Photoanodes with H-TiO2
      nanocrystals hydrogenated at 300  degrees C show the highest short-circuit
      current density (Jsc) of 18.92 mA cm(-2) and photoelectrical conversion
      efficiency of 7.76% under standard AM 1.5 global solar irradiation, indicating a
      27 and 28% enhancement in Jsc and eta, respectively, in comparison to those with
      TiO2. The enhancement is attributed to high donor density, narrow band gap and
      positive shift of flat band energy (Vfb) of H-TiO2 that promote the driving force
      for electron injection. Intensity-modulated photocurrent spectroscopy (IMPS)
      accompanied by intensity-modulated photovoltage spectroscopy (IMVS) and other
      analyses were applied to shed more light on the fundamental mechanisms inside the
      charge transfer and transport in these systems. 

PMID- 25621976
TI  - Analysis of Japanese radionuclide monitoring data of food before and after the
      Fukushima nuclear accident.
AB  - In an unprecedented food monitoring campaign for radionuclides, the Japanese
      government took action to secure food safety after the Fukushima nuclear accident
      (Mar. 11, 2011). In this work we analyze a part of the immense data set, in
      particular radiocesium contaminations in food from the first year after the
      accident. Activity concentrations in vegetables peaked immediately after the
      campaign had commenced, but they decreased quickly, so that by early summer 2011
      only a few samples exceeded the regulatory limits. Later, accumulating mushrooms
      and dried produce led to several exceedances of the limits again. Monitoring of
      meat started with significant delay, especially outside Fukushima prefecture.
      After a buildup period, contamination levels of meat peaked by July 2011 (beef).
      Levels then decreased quickly, but peaked again in September 2011, which was
      primarily due to boar meat (a known accumulator of radiocesium). Tap water was
      less contaminated; any restrictions for tap water were canceled by April 1, 2011.
      Pre-Fukushima (137)Cs and (90)Sr levels (resulting from atmospheric nuclear
      explosions) in food were typically lower than 0.5 Bq/kg, whereby meat was
      typically higher in (137)Cs and vegetarian produce was usually higher in (90)Sr.
      The correlation of background radiostrontium and radiocesium indicated that the
      regulatory assumption after the Fukushima accident of a maximum activity of
      (90)Sr being 10% of the respective (137)Cs concentrations may soon be at risk, as
      the (90)Sr/(137)Cs ratio increases with time. This should be taken into account
      for the current Japanese food policy as the current regulation will soon
      underestimate the (90)Sr content of Japanese foods. 

PMID- 25621978
TI  - Positive interventions: An emotion regulation perspective.
AB  - The rapid growth of the literature on positive interventions to increase
      "happiness" has suggested the need for an overarching conceptual framework to
      integrate the many and apparently disparate findings. In this review, we used the
      process model of emotion regulation (Gross, 1998) to organize the existing
      literature on positive interventions and to advance theory by clarifying the
      mechanisms underlying their effectiveness. We have proposed that positive
      emotions can be increased both in the short- and longer-term through 5 families
      of emotion regulation strategies (i.e., situation selection, situation
      modification, attentional deployment, cognitive change, and response modulation),
      showing how these emotion regulation strategies can be applied before, during,
      and after positive emotional events. Regarding short-term increases in positive
      emotions, our review found that attentional deployment, cognitive change, and
      response modulation strategies have received the most empirical support, whereas
      more work is needed to establish the effectiveness of situation selection and
      situation modification strategies. Regarding longer-term increases in positive
      emotions, strategies such as situation selection during an event and attentional
      deployment before, during, and after an event have received strong empirical
      support and are at the center of many positive interventions. However, more work
      is needed to establish the specific benefits of the other strategies, especially
      situation modification. We argue that our emotion regulation framework clarifies
      existing interventions and points the way for new interventions that might be
      used to increase positive emotions in both nonclinical and clinical populations.

PMID- 25621979
TI  - Cerebrospinal fluid drainage and induced hypertension improve spinal cord
      perfusion after acute spinal cord injury in pigs.
AB  - BACKGROUND: Acute spinal cord injury (SCI) is commonly treated by elevating the
      mean arterial pressure (MAP). Other potential interventions include cerebrospinal
      fluid drainage (CSFD). OBJECTIVE: To determine the efficacy of aggressive MAP
      elevation combined with intrathecal pressure (ITP) reduction; our primary
      objective was to improve spinal cord blood flow (SCBF) after SCI. METHODS: All 15
      pigs underwent laminectomy. Study groups included control (n = 3); SCI only (n =
      3); SCI combined with MAP elevation (SCI + MAP) (n = 3); SCI combined with CSFD
      (SCI + CSFD) (n = 3); and SCI combined with both MAP elevation and CSFD (SCI +
      MAP + CSFD) (n = 3). SCBF was measured with laser Doppler flowmetry. RESULTS: In
      the SCI group, SCBF decreased by 56% after SCI. MAP elevation after SCI resulted
      in a 34% decrease in SCBF, whereas CSFD resulted in a 59% decrease in SCBF. The
      combination of CSFD and MAP elevation resulted in a 24% increase in SCBF. The SCI
      + MAP group had an average ITP increase of 5.45 mm Hg after MAP elevation 1 hour
      after SCI and remained at that level throughout the experiment. CONCLUSION: Both
      MAP elevation alone and CSFD alone led to only short-term improvement of SCBF.
      The combination of MAP elevation and CSFD significantly and sustainably improved
      SCBF and spinal cord perfusion pressure. Although laser Doppler flowmetry can
      provide flow measurements to a tissue depth of only 1.5 mm, these results may
      represent pattern of blood flow changes in the entire spinal cord after injury.

PMID- 25621980
TI  - Balloon remodeling may improve angiographic results of stent-assisted coiling of
      unruptured intracranial aneurysms.
AB  - BACKGROUND: Endovascular treatment of wide-necked and complex aneurysms may
      require stent-assisted coiling, either as primary stenting or combined with the
      balloon remodeling technique (BRT). OBJECTIVE: To compare the angiographic
      results and clinical outcomes of both strategies in the Safety and Efficacy of
      Neuroform for Treatment of intracranial Aneurysms (SENAT) registry. METHODS:
      SENAT was a prospective, multicenter registry that allowed BRT in conjunction
      with stenting and coiling with bare platinum coils. Clinical and angiographic
      outcomes of 97 patients with unruptured aneurysms treated with stenting, 51 after
      BRT (BRT+) and 46 without balloon assistance (BRT-), were retrieved from the
      SENAT database. Technical, clinical, and angiographic outcomes were compared
      between the 2 groups. RESULTS: Periprocedural morbimortality and midterm clinical
      outcomes were not different between groups. Residual aneurysms were observed in
      7.8% of BRT+ and in 21.7% of BRT- (P = .08) at the end of the stenting procedure.
      Four retreatments were performed during the follow-up period (2 BRT+, 2 BRT-).
      Twelve- to 18-month anatomic results showed a significant difference between
      groups, with a residual aneurysm being observed in 6.1% of BRT+ as compared to
      22.7% of BRT- patients (P = .03). CONCLUSION: Primary BRT followed by stent
      assisted coiling may be associated with fewer residual aneurysms at 12 to 18
      months as compared to stent-assisted coiling alone.

PMID- 25621981
TI  - Initial experience using awake surgery for glioma: oncological, functional, and
      employment outcomes in a consecutive series of 25 cases.
AB  - BACKGROUND: Awake glioma surgery aims to maximize resection to optimize prognosis
      while minimizing the risk of postoperative deficits. OBJECTIVE: To evaluate
      oncological, functional, and employment outcomes in the first cohort of patients
      having this type of surgery at our institution and to determine the effects of
      any learning curve. METHODS: All cases of awake adult (>18 years of age) glioma
      surgery were recorded between the introduction of this technique in 2011 until
      the end of 2013. Extent of tumor resection was quantified on magnetic resonance
      imaging and compared with the objective prediction from a resection probability
      map. Cognitive status was assessed preoperatively and at 3 months
      postoperatively. Patients were questioned about their job and capability of
      working before and after surgery. RESULTS: Twenty-five patients were included in
      the analysis. No new motor or language deficits were noted at 6 weeks after
      surgery. Postoperative magnetic resonance imaging showed complete resection in 11
      of 13 patients with glioblastoma and >98% resection in the other 2 patients. For
      patients with World Health Organization grade II glioma, 3 had total, 4 had
      subtotal, and 3 had partial resections. Comparison between cognitive levels
      before and after surgery showed no change in 4 patients, improvement in some
      tests in 2 patients, and deterioration in some tests in 3 patients. Of 20
      patients working at the time of diagnosis, 16 returned to work. CONCLUSION: These
      oncological and functional results of awake glioma surgery during the learning
      curve are comparable to results from established centers. The use and utility of
      resection probability maps are well demonstrated. The return to work level is
      high.

PMID- 25621982
TI  - Acute stroke after carotid endarterectomy: time for a paradigm shift? Multicenter
      experience with emergent carotid artery stenting with or without intracranial
      tandem occlusion thrombectomy.
AB  - BACKGROUND: Stroke in the immediate postoperative period after carotid
      endarterectomy is a rare complication. Many centers have begun incorporating
      angiography before surgical re-exploration, which has the advantage of confirming
      carotid occlusion and treating tandem intracranial lesions if present. OBJECTIVE:
      To determine the safety and efficacy of this strategy. METHODS: A retrospective
      review was performed of all patients undergoing acute stenting of the carotid
      artery after carotid endarterectomy from November 2009 to June 2013 at 4 centers.
      Charts and angiographic images were reviewed. Eleven cases of carotid thrombosis
      within 72 hours of carotid endarterectomy and subsequent treatment strategies are
      summarized. RESULTS: All patients had >50% carotid stenosis before carotid
      endarterectomy. One patient had intraoperative occlusion and dissection of the
      internal carotid artery, which was noted on intraoperative carotid duplex
      ultrasound. All patients underwent postoperative computed tomography or computed
      tomography perfusion scans with subsequent cerebral angiography and stent
      reconstruction within 11 hours of symptom onset. In all cases, carotid
      recanalization was successfully completed between 32 and 160 minutes from groin
      puncture. There were no procedural complications. Four patients had a tandem
      middle cerebral artery occlusion, 3 of whom underwent successful recanalization.
      CONCLUSION: Emergent endovascular evaluation in the setting of acute post-
      carotid endarterectomy thrombosis is a safe and timely treatment option, with the
      benefit of detecting and treating embolic intracranial lesions. Immediate
      angiography and intervention in this rare surgical complication show promising
      initial results.

PMID- 25621983
TI  - Pathophysiology of acute cerebrovascular syndrome in patients with carotid artery
      stenosis: a magnetic resonance imaging/single-photon emission computed tomography
      study.
AB  - BACKGROUND: The mechanisms underlying acute cerebrovascular syndrome in patients
      with carotid artery stenosis remain unclear. OBJECTIVE: To assess the
      relationships among infarct localization, hemodynamics, and plaque components.
      METHODS: This prospective study included 38 patients with acute cerebrovascular
      syndrome resulting from ipsilateral carotid artery stenosis. Cerebral infarct
      localization was categorized into 3 patterns (cortical, border zone, and mixed
      pattern). Carotid plaque components were evaluated with T1-weighted magnetic
      resonance imaging and time-of-flight imaging. Cerebral blood flow (CBF) and
      cerebrovascular reactivity (CVR) were also quantified. RESULTS: Infarcts were
      identified in 38 patients with the use of diffusion-weighted magnetic resonance
      imaging. On the basis of the assessment of hemodynamics, the cortical pattern was
      seen in 18 of 21 patients with type 1 ischemia (normal CBF, normal CVR), whereas
      the mixed pattern was seen in 2 patients with type 2 ischemia (normal CBF,
      impaired CVR) and 12 of 15 patients with type 3 ischemia (impaired CBF, impaired
      CVR). The plaque components were categorized into fibrous (4 patients), lipid
      rich (14 patients), and intraplaque hemorrhage (IPH; 20 patients). Of the
      patients with fibrous plaque, 2 had border-zone and 2 had mixed-pattern infarcts.
      Of the patients with lipid-rich plaque, 7 had cortical and 6 had mixed-pattern
      infarcts. Of patients with intraplaque hemorrhage, 11 had cortical and 9 had
      mixed-pattern infarcts. CONCLUSION: Cortical infarction occurs as a result of
      vulnerable plaque. Reduced cerebral perfusion induces border-zone infarction.
      Both factors are implicated in mixed-pattern infarction. Developments in
      noninvasive diagnostic modalities allow us to explore the mechanisms behind acute
      cerebrovascular syndrome in carotid artery stenosis and to determine the ideal
      therapies.

PMID- 25621984
TI  - Stratification of recanalization for patients with endovascular treatment of
      intracranial aneurysms.
AB  - BACKGROUND: With the increasing use of endovascular techniques in the treatment
      of both ruptured and unruptured intracranial aneurysms, the issue of obliteration
      efficacy has become increasingly important. OBJECTIVE: To systematically develop
      a comprehensive model for predicting retreatment with various types of
      endovascular treatment. METHODS: We retrospectively reviewed medical records that
      were prospectively collected for 305 patients who received endovascular treatment
      for intracranial aneurysms from 2007 to 2013. Multivariable logistic regression
      was performed on candidate predictors identified by univariable screening
      analysis to detect independent predictors of retreatment. A composite risk score
      was constructed based on the proportional contribution of independent predictors
      in the multivariable model. RESULTS: Size (>10 mm), aneurysm rupture, stent
      assistance, and posttreatment degree of aneurysm occlusion were independently
      associated with retreatment, whereas intraluminal thrombosis and flow diversion
      demonstrated a trend toward retreatment. The Aneurysm Recanalization
      Stratification Scale was constructed by assigning the following weights to
      statistically and clinically significant predictors: aneurysm-specific factors:
      size (>10 mm), 2 points; rupture, 2 points; presence of thrombus, 2 points.
      Treatment-related factors were stent assistance, -1 point; flow diversion, -2
      points; Raymond Roy occlusion class 2, 1 point; Raymond Roy occlusion class 3, 2
      points. This scale demonstrated good discrimination with a C-statistic of 0.799.
      CONCLUSION: Surgical decision making and patient-centered informed consent
      require comprehensive and accessible information on treatment efficacy. We
      constructed the Aneurysm Recanalization Stratification Scale to enhance this
      decision-making process. This is the first comprehensive model that has been
      developed to quantitatively predict the risk of retreatment after endovascular
      therapy.

PMID- 25621985
TI  - Lumbar intrafacet bone dowel fixation.
AB  - BACKGROUND: The efficacy of intrafacet bone dowels in promoting lumbar fusion has
      not been established. A recently published study indicates a low fusion rate,
      along with device migration. OBJECTIVE: To evaluate the mechanical stability of 2
      lumbar facet fixation technologies before and after repeated cyclic loading.
      METHODS: Six human lumbar specimens were implanted with both types of allograft,
      one at L2-3 and the other at L4-5, on a randomized basis. All specimens were
      subjected to pure-moment flexibility testing before and after implantation and
      after 2500 and 5000 cycles of flexion-extension bending. Each specimen was
      scanned with computed tomography before and after cyclic loading to measure
      device migration. RESULTS: Only dowel 1 resulted in a statistically significant
      reduction in flexion-extension range of motion at the treatment level. This
      reduction was significant at baseline testing (P = .03) and after 2500 cycles of
      flexion-extension loading (P = .048) but was not significant after 5000 cycles of
      loading. One of the bone dowels extruded posteriorly out of the joint space
      during baseline axial torsion flexibility testing, which was before any cyclic
      loading. CONCLUSION: The data obtained in this study do not indicate efficacy of
      fixation for cylindrical bone dowels in the lumbar facet joint. Significant
      fixation was detected only for one of the devices and was no longer present after
      a relatively short duration of repeated loading. Furthermore, considerable
      magnitudes of device migration were detected.

PMID- 25621986
TI  - Letter: facetal orientation in congenital atlantoaxial dislocation: there are
      angles and there are "angles".

PMID- 25621987
TI  - In reply: volumetric arc therapy (RapidArc) vs Gamma Knife radiosurgery for
      multiple brain metastases.

PMID- 25621988
TI  - A comparison of methodologies to test aggression in zebrafish.
AB  - Aggression is a psychological construct that is commonly used to classify
      zebrafish behavior. Aggression is a complex trait that can be difficult to
      accurately measure. The literature on fish behavior describes many different
      methodologies to examine aggression, which, we believe, have not been compared in
      a formal manner. In this study we observed 19 individual zebrafish (Danio rerio)
      and quantified bites, lateral displays, charges, darts, and time near the
      stimulus in six common assays used to measure aggression. The methodologies
      included an inclined mirror assay, two flat mirror assays with different
      acclimation periods, a live conspecific assay, a clay model stimulus assay, and a
      video recording assay. Our results indicate high repeatability in most aggressive
      behaviors over time, which confirms the value of each assay to measure
      personality. However, our results also indicate significant differences between
      the assays. Specifically, assays using a flat mirror or live conspecific as a
      stimulus for aggression elicited more attempted bites than an inclined mirror, a
      clay model stimulus, or a video recording stimulus. Furthermore, the inclined
      mirror stimulus provoked more darts than any other assay. The results suggest the
      need for researchers to consider specific research goals when selecting the
      appropriate stimulus to provoke aggression in zebrafish. 

PMID- 25621989
TI  - African baobabs with false inner cavities: the radiocarbon investigation of the
      Lebombo Eco Trail baobab.
AB  - The article reports the radiocarbon investigation results of the Lebombo Eco
      Trail tree, a representative African baobab from Mozambique. Several wood samples
      collected from the large inner cavity and from the outer part of the tree were
      investigated by AMS radiocarbon dating. According to dating results, the age
      values of all samples increase from the sampling point with the distance into the
      wood. For samples collected from the cavity walls, the increase of age values
      with the distance into the wood (up to a point of maximum age) represents a major
      anomaly. The only realistic explanation for this anomaly is that such inner
      cavities are, in fact, natural empty spaces between several fused stems disposed
      in a ring-shaped structure. We named them false cavities. Several important
      differences between normal cavities and false cavities are presented. Eventually,
      we dated other African baobabs with false inner cavities. We found that this new
      architecture enables baobabs to reach large sizes and old ages. The radiocarbon
      date of the oldest sample was 1425 +/- 24 BP, which corresponds to a calibrated
      age of 1355 +/- 15 yr. The dating results also show that the Lebombo baobab
      consists of five fused stems, with ages between 900 and 1400 years; these five
      stems build the complete ring. The ring and the false cavity closed 800-900 years
      ago. The results also indicate that the stems stopped growing toward the false
      cavity over the past 500 years. 

PMID- 25621990
TI  - Prediction of adaptive self-regulatory responses to arthritis pain anxiety in
      exercising adults: does pain acceptance matter?
AB  - BACKGROUND: Exercising for >= 150 min/week is a recommended strategy for self
      managing arthritis. However, exercise nonadherence is a problem. Arthritis pain
      anxiety may interfere with regular exercise. According to the fear-avoidance
      model, individuals may confront their pain anxiety by using adaptive self
      regulatory responses (eg, changing exercise type or duration). Furthermore, the
      anxiety-self-regulatory responses relationship may vary as a function of
      individuals' pain acceptance levels. OBJECTIVES: To investigate pain acceptance
      as a moderator of the pain anxiety-adaptive self-regulatory responses
      relationship. The secondary objective was to examine whether groups of patients
      who differed in meeting exercise recommendations also differed in pain-related
      and self-regulatory responses. METHODS: Adults (mean [+/- SD] age 49.75 +/- 13.88
      years) with medically diagnosed arthritis completed online measures of arthritis
      pain-related variables and self-regulatory responses at baseline, and exercise
      participation two weeks later. Individuals meeting (n=87) and not meeting (n=49)
      exercise recommendations were identified. RESULTS: Hierarchical multiple
      regression analysis revealed that pain acceptance moderated the anxiety-adaptive
      self-regulatory responses relationship. When pain anxiety was lower, greater pain
      acceptance was associated with less frequent use of adaptive responses. When
      anxiety was higher, adaptive responses were used regardless of pain acceptance
      level. MANOVA findings revealed that participants meeting the recommended
      exercise dose reported significantly lower pain and pain anxiety, and greater
      pain acceptance (P<0.05) than those not meeting the dose. CONCLUSIONS: Greater
      pain acceptance may help individuals to focus their efforts to adapt to their
      pain anxiety only when it is higher, leaving self-regulatory capacity to cope
      with additional challenges to exercise adherence (eg, busy schedule).

PMID- 25621991
TI  - Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives
      as cholinesterase and beta-amyloid aggregation inhibitors with neuroprotective
      properties.
AB  - The presented study describes the synthesis, pharmacological evaluation (AChE and
      BuChE inhibition, beta amyloid anti-aggregation effect and neuroprotective
      effect), molecular modeling and crystallographic studies of a novel series of
      isoindoline-1,3-dione derivatives. The target compounds were designed as dual
      binding site acetylcholinesterase inhibitors with an arylalkylamine moiety
      binding at the catalytic site of the enzyme and connected via an alkyl chain to a
      heterocyclic fragment, capable of binding at the peripheral anionic site of AChE.
      Among these molecules, compound 15b was found to be the most potent and selective
      AChE inhibitor (IC50EeAChE = 0.034 MUM). Moreover, compound 13b in addition to
      AChE inhibition (IC50 EeAChE = 0.219 MUM) possesses additional properties, such
      as the ability to inhibit Abeta aggregation (65.96% at 10 MUM) and a
      neuroprotective effect against Abeta toxicity at 1 and 3 MUM. Compound 13b
      emerges as a promising multi-target ligand for the further development of the
      therapy for age-related neurodegenerative disorders.

PMID- 25621992
TI  - Correlation of the antimicrobial activity of salicylaldehydes with broadening of
      the NMR signal of the hydroxyl proton. Possible involvement of proton exchange
      processes in the antimicrobial activity.
AB  - Certain substituted salicylaldehydes are potent antibacterial and antifungal
      agents and some of them merit consideration as potential chemotherapeutic agents
      against Candida infections, but their mechanism of action has remained obscure.
      We report here a distinct correlation between broadening of the NMR signal of the
      hydroxyl proton of salicylaldehydes and their activity against several types of
      bacteria and fungi. When proton NMR spectra of the compounds were determined
      using hexadeuterodimethylsulfoxide as solvent and the height of the OH proton
      signal was measured, using the signal of the aldehyde proton as an internal
      standard, it was discovered that a prerequisite of potent antimicrobial activity
      is that the proton signal is either unobservable or relatively very low, i.e.
      that it is extremely broadened. Thus, none of the congeners whose OH proton
      signal was high were potent antimicrobial agents. Some congeners that gave a very
      low OH signal were, however, essentially inactive against the microbes,
      indicating that although drastic broadening of the OH signal appears to be a
      prerequisite, also other (so far unknown) factors are needed for high
      antimicrobial activity. Because broadening of the hydroxyl proton signal is
      related to the speed of the proton exchange process(es) involving that proton,
      proton exchange may be involved in the mechanism of action of the compounds.
      Further studies are needed to analyze the relative importance of different
      factors (such as electronic effects, strength of the internal hydrogen bond, co
      planarity of the ring and the formyl group) that determine the rates of those
      processes. 

PMID- 25621994
TI  - Structure of the oxygen evolving complex of Photosystem II at room temperature.
AB  - The functional structure of the Oxygen Evolving Complex, the Mn4Ca cluster of
      Photosystem II, a critical component of natural photosynthesis, was analyzed at
      room temperature by EXAFS. An experimental improvement in the form of a spinning
      sample holder allowed us to efficiently counteract the severe X-ray damage
      sensitivity of Photosystem II to obtain high quality data subsequently used for a
      systematic evaluation of atomistic S1 state models. We investigated the accuracy
      of models collected by both conventional and femtosecond XRD at 1.9 and 1.95 A
      resolution, respectively, as well as DFT-based models, to determine the structure
      most representative of experimental data. Additionally, room temperature EXAFS
      results do not show a visible reduction in the intensity of the k-space
      oscillations, supporting a rigid structure of the Mn4Ca cluster at room
      temperature. 

PMID- 25621993
TI  - A Whole of Population, Multiuser Series of High-Intensity Focused Ultrasound for
      Management of Localized Prostate Cancer: Outcomes and Implications.
AB  - PURPOSE: To determine the oncologic and complication outcomes of treatment of
      patients with localized prostate cancer by high intensity focused ultrasound
      (HIFU) for primary management of prostate cancer in a whole of population,
      multiuser series. PATIENTS AND METHODS: We created a centralized database
      accessible only by nonurologist researchers-within a cancer epidemiology center,
      after ethics approval from that institution. A single researcher prospectively
      entered baseline, treatment, and clinical/biochemical follow-up data from all
      patients treated with HIFU in the state of Victoria over the study period.
      RESULTS: We accrued 108 patients, of whom 103 had been staged as having
      clinically localized disease. Ninety-three patients (86.1%) had low- or
      intermediate-risk prostate cancer. Forty-four patients (40.5%) had persistent
      mild urinary incontinence at 3 months after treatment, and 3 of these ultimately
      underwent further surgical procedures to correct incontinence. Twenty-seven
      patients (25%) additionally experienced occasions of urinary retention in the
      first 3 months after treatment because of passage of tissue. Twenty-nine patients
      had achieved a prostate-specific antigen level of <0.2 ng/mL at 3 months after
      HIFU. Fifty-six patients underwent post-HIFU prostate biopsy, and this was
      positive for residual cancer in 51 cases. Forty-five of the patients who had a
      positive post-HIFU biopsy underwent secondary treatment for prostate cancer.
      CONCLUSION: Oncologic control and complication outcomes in this cohort were
      inferior to those previously reported for HIFU in single-user series. Given the
      population-based multiuser nature of our series, we believe our observations are
      more likely to reflect the community outcomes that might be expected from
      widespread adoption of HIFU than generalizing from single-operator series.

PMID- 25621995
TI  - Novel KAT6B-KANSL1 fusion gene identified by RNA sequencing in retroperitoneal
      leiomyoma with t(10;17)(q22;q21).
AB  - Retroperitoneal leiomyoma is a rare type of benign smooth muscle tumor almost
      exclusively found in women and with histopathological features similar to uterine
      leiomyomas. The pathogenesis of retroperitoneal leiomyoma is unclear and next to
      nothing is known about the cytogenetics and molecular genetics of the tumor. Here
      we present the first cytogenetically analyzed retroperitoneal leiomyoma. It had a
      t(10;17)(q22;q21) as the sole chromosomal abnormality. Using RNA-Sequencing and
      the 'grep' command to search the fastq files of the sequence data we found that
      the translocation resulted in fusion of the genes KAT6B (10q22) with KANSL1
      (17q21). RT-PCR together with direct (Sanger) sequencing verified the presence of
      a KAT6B-KANSL1 fusion transcript. No reciprocal KANSL1-KAT6B transcript was
      amplified suggesting that it was either absent or unexpressed. The KAT6B-KANSL1
      fusion transcript consists of exons 1 to 3 of KAT6B and exons 11 to 15 of KANSL1,
      is 3667 bp long, has a 1398 bp long open reading frame, and codes for a 466 amino
      acid residue protein. The corresponding KAT6B-KANSL1 protein contains the NEMM
      domain (including the linker histone H1/H5, domain H15) of KAT6B and the PEHE
      domain of KANSL1. The function of the fusion protein might be regulation of
      transcription with an affinity for chromatin (linker histone H1/H5) and
      interaction with the HAT domain of KAT8 (PEHE domain). The tumor expressed HMGA2
      and HMGA1 even though 12q14-15 and 6p looked normal by G-banding analysis. The
      tumor also expressed MED12 in the absence of exon 2 mutations. Overall, the data
      show that the examined retroperitoneal leiomyoma resembles a subset of uterine
      leiomyomas in terms of histology and genetics. 

PMID- 25621997
TI  - An integrated quantitative and targeted proteomics reveals fitness mechanisms of
      Aeromonas hydrophila under oxytetracycline stress.
AB  - To date, above ten thousand tons of antibiotics are used in aquaculture each year
      that lead to the deterioration of natural resources. However, knowledge is
      limited on the molecular biological behavior of common aquatic pathogens against
      antibiotics stress. In this study, proteomics profiles of Aeromonas hydrophila,
      which were exposed to different levels of oxytetracycline (OXY) stress, were
      displayed and compared using iTRAQ labeling and SWATH-MS based LC-MS/MS methods.
      A total 1383 proteins were identified by SWATH-MS method, and 2779 proteins were
      identified from iTRAQ labeling samples. There are 152 up-regulated and 52 down
      regulated proteins overlapped in 5 MUg/mL OXY stress and both 83 up- and down
      regulated proteins overlapped in 10 MUg/mL OXY stress in both methods,
      respectively. Results show that many protein synthesis and translation related
      proteins increased, while energy generation related proteins decreased in OXY
      stress. The varieties of selected proteins involved in both pathways were further
      validated by sMRM(HR), q-PCR, and enzyme activity assay. Furthermore, the
      concentrations of NAD+ and NADH were measured to verify the characteristic of
      energy generation process in OXY stress and OXY resistance strain. We demonstrate
      that the down-regulation of energy generation related metabolic pathways and up
      regulation of translation may play an important role in antibiotics fitness or
      resistance of aquatic pathogens. 

PMID- 25621996
TI  - In vivo molecular imaging and radionuclide (131I) therapy of human nasopharyngeal
      carcinoma cells transfected with a lentivirus expressing sodium iodide symporter.
AB  - INTRODUCTION: Despite recent improvements in the survival rates for
      nasopharyngeal carcinoma (NPC), novel treatment strategies are required to
      improve distant metastasis-free survival. The sodium iodine symporter (NIS) gene
      has been applied for in vivo imaging and cancer therapy. In this study, we
      examined the potential of NIS gene therapy as a therapeutic approach in NPC by
      performing non-invasive imaging using 125I and 131I therapy in vivo. METHODS: We
      constructed a lentiviral vector expressing NIS and enhanced green fluorescent
      protein (EGFP) under the control of the human elongation factor-1alpha (EF1alpha)
      promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE
      2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude
      mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT
      imaging; the therapeutic effects of treatment with 131I were assessed over 25
      days by measuring tumor volume and immunohistochemical staining of the excised
      tumors. RESULTS: qPCR, immunofluorescence and Western blotting confirmed that CNE
      2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and
      xenografts took up and accumulated significantly more 125I than CNE-2Z cells and
      xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE
      2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS
      xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells
      expressed higher levels of NIS and caspase-3 and lower levels of Ki-67.
      CONCLUSION: Lentiviruses effectively delivered and mediated long-lasting
      expression of NIS in CNE-2Z cells which enabled uptake and accumulation of
      radioisotopes and provided a significant therapeutic effect in an in vivo model
      of NPC. NIS-mediated radioiodine treatment merits further investigation as a
      potentially effective, low toxicity therapeutic strategy for NPC.

PMID- 25621998
TI  - Antibody modified gold nano-mushroom arrays for rapid detection of alpha
      fetoprotein.
AB  - Localized surface plasmon resonance (LSPR) combined with immunoassay shows
      greatly potential in fast detection of tumor markers. In this paper, a highly
      sensitive LSPR substrate has been fabricated and modified for direct detection of
      alpha-fetoprotein (AFP). The biosensor was prepared by interference lithography,
      and modified by covalently immobilizing anti-AFP on the surface of gold nano
      mushroom arrays (GNMA). The modification process was investigated by Vis-NIR
      reflectance spectra and cyclic voltammogram measurements. We revealed the optical
      properties of the modified GNMA by measuring the Vis-NIR reflectance spectra and
      simulating its electric intensity field distribution under light illumination.
      The GNMA substrate was highly sensitive, with a refractive index sensitivity of
      ~465 nm/RIU. The substrate can be applied to label-free detection of AFP, with
      the linear range and the limit of detection determined to be 20-200 ng/mL and 24
      ng/mL (S/N=3), respectively. We also demonstrated its clinical application by
      directly detecting AFP in human serum samples. It is expected that our biosensor
      could be integrated on microfluidic chips for high-throughput detection in
      portable early diagnosis, post-operative and point-of-care (POC) in clinical
      applications.

PMID- 25621999
TI  - Colorimetric detection of microcystin-LR based on disassembly of orient
      aggregated gold nanoparticle dimers.
AB  - Recently we demonstrated oriented formation of gold nanoparticle (AuNP) dimers
      for ultrasensitive sensing oligonucleotides (J. Am. Chem. Soc. 2013, 135, 12338).
      Herein, we investigate the reverse process of this sensing mechanism using target
      analytes to disassemble the orient-aggregated AuNP dimers. This enables us to
      expand the analytes from oligonucleotides to other molecules, e.g. highly
      sensitive and selective determination of microcystin-LR (MC-LR) is selected for a
      demonstration in this work. Aptamers specific to the target molecules are used as
      linkers to prepare the AuNP dimers. In the presence of the target molecule, the
      aptamer changes its structure to bind the target molecule. Thus the pre-formed
      AuNP dimers are disassembled. As a result, the solution color is changed from
      blue to red. This sensing design retains the advantages of the previously
      developed sensors based on target molecules guided formation of AuNP dimers, e.g.
      the overwhelming sensitivity and stability comparing with those non-oriented
      sensors based on the formation of large aggregates, with the additional
      advantages as follows: 1) the target molecules are expanded from oligonucleotides
      to arbitrary molecules that can specifically bind to aptamers; 2) the color
      change is completed within 5 min, while the previous sensor based on the
      formation of AuNP dimers cost ~1 hour to obtain stable responses.

PMID- 25622000
TI  - Total synthesis of (+)-vibsanin A.
AB  - The first total synthesis of (+)-vibsanin A, an 11-membered vibsane diterpenoid,
      was achieved, unambiguously establishing its relative and absolute
      stereochemistry. Highlights of the synthesis include the stereoselective
      formation of an all-carbon quaternary stereocenter by a zinc-mediated Barbier
      type allylation in an aqueous medium, and the efficient construction of an 11
      membered ring skeleton by a combination of an intramolecular Nozaki-Hiyama-Kishi
      (NHK) reaction and a Mitsunobu reaction. 

PMID- 25622001
TI  - Calcium carbonate nucleation driven by ion binding in a biomimetic matrix
      revealed by in situ electron microscopy.
AB  - The characteristic shapes, structures and properties of biominerals arise from
      their interplay with a macromolecular matrix. The developing mineral interacts
      with acidic macromolecules, which are either dissolved in the crystallization
      medium or associated with insoluble matrix polymers, that affect growth habits
      and phase selection or completely inhibit precipitation in solution. Yet little
      is known about the role of matrix-immobilized acidic macromolecules in directing
      mineralization. Here, by using in situ liquid-phase electron microscopy to
      visualize the nucleation and growth of CaCO3 in a matrix of polystyrene
      sulphonate (PSS), we show that the binding of calcium ions to form Ca-PSS
      globules is a key step in the formation of metastable amorphous calcium carbonate
      (ACC), an important precursor phase in many biomineralization systems. Our
      findings demonstrate that ion binding can play a significant role in directing
      nucleation, independently of any control over the free-energy barrier to
      nucleation. 

PMID- 25622002
TI  - Temperature diagnostic to identify high risk areas and optimize Legionella
      pneumophila surveillance in hot water distribution systems.
AB  - Legionella pneumophila is frequently detected in hot water distribution systems
      and thermal control is a common measure implemented by health care facilities. A
      risk assessment based on water temperature profiling and temperature distribution
      within the network is proposed, to guide effective monitoring strategies and
      allow the identification of high risk areas. Temperature and heat loss at control
      points (water heater, recirculation, representative points-of-use) were monitored
      in various sections of five health care facilities hot water distribution systems
      and results used to develop a temperature-based risk assessment tool. Detailed
      investigations show that defective return valves in faucets can cause widespread
      temperature losses because of hot and cold water mixing. Systems in which water
      temperature coming out of the water heaters was kept consistently above 60 
      degrees C and maintained above 55  degrees C across the network were negative for
      Legionella by culture or qPCR. For systems not meeting these temperature
      criteria, risk areas for L. pneumophila were identified using temperature
      profiling and system's characterization; higher risk was confirmed by more
      frequent microbiological detection by culture and qPCR. Results confirmed that
      maintaining sufficiently high temperatures within hot water distribution systems
      suppressed L. pneumophila culturability. However, the risk remains as shown by
      the persistence of L. pneumophila by qPCR. 

PMID- 25622004
TI  - Removal of selenium from water with nanoscale zero-valent iron: mechanisms of
      intraparticle reduction of Se(IV).
AB  - Increasing evidences suggest that nanoscale zero-valent iron (nZVI) is an
      effective agent for treatment and removal of selenium from water. For example,
      1.3 mM selenite was quickly removed from water within 3 min with 5 g/L nZVI. In
      this work, reaction mechanisms of selenite [Se(IV)] in a single core-shell
      structured nanoscale zero-valent iron (nZVI) particle were studied with the
      method of spherical aberration corrected scanning transmission electron
      microscopy (Cs-STEM) integrated with X-ray energy dispersive spectroscopy (XEDS).
      This method was utilized to visualize solid phase translocation and
      transformation of Se(IV) such as diffusion, reduction, deposition and the effect
      of surface defects in a single nanoparticle. Se(IV) was reduced to Se(-II) and
      Se(0), which then formed a 0.5 nm layer of selenium at the iron oxide-Fe(0)
      interface at a depth of 6 nm from the surface. The results provided near atomic
      resolution proof on the intraparticle diffusion-reduction of Se(IV) induced by
      nZVI. The STEM mapping also discovered that defects on the surface layer
      accelerate the diffusion of selenium and increase the capacity of nZVI for
      selenium sequestration. 

PMID- 25622003
TI  - UV and hydrogen peroxide treatment restores changes in innate immunity caused by
      exposure of fish to reuse water.
AB  - The purpose of this study was to assess the innate immunity of goldfish exposed
      to reuse water, and UV/H2O2-treated reuse water, using a real-time flow-through
      exposure system. The reuse water generated by ultrafiltration of finished
      wastewater from the municipal wastewater treatment plant was analyzed for the
      presence of a panel of 20 herbicides/fungicides and 46 pharmaceuticals and
      personal care products (PPCP). There was a seasonal variation in the profile and
      concentrations of xenobiotics in reuse water with lowest levels occurring in the
      summer. The innate immunity parameters assessed were cytokine (IFNgamma, IL
      1beta, IL-10, TNFalpha2), and cytokine receptor (TNFR1, TNFR2, IFNGR1, IFNGR2)
      gene expression, and phagocytosis of kidney leukocyte subpopulations. Assessment
      of innate immunity parameters was done after acute (7 days) and sub chronic (30
      and 60 days) exposure to reuse water, UV/H2O2-treated reuse water, and activated
      carbon-treated reuse water (ACT; control), during spring, summer and fall of
      2012. Temporal (acute versus sub chronic) as well as seasonal differences in
      innate immunity of fish exposed to reuse water were observed. The acute exposure
      of fish to reuse water caused significant down-regulation in cytokine gene
      expression in different organs of fish (kidney, spleen, liver) and phagocytic
      ability of different kidney leukocyte subpopulations. The immune gene expression
      and phagocytosis of kidney leukocytes of fish returned to ACT control levels
      after sub chronic exposure suggesting that fish have habituated to the reuse
      water exposure. The changes in gene expression after acute exposure were related
      to variations in the profile of xenobiotics in reuse water during different
      seasons. The efficiency of xenobiotic removal using UV/H2O2 ranged between 1.6
      and 100% indicating that treatment of reuse water using high dose UV/H2O2 was
      only partially effective in removing the xenobiotics, as assessed by both
      chemical analyses and measurement of innate immune responsiveness of the fish.
      Furthermore, exposure of fish to reuse water and UV/H2O2-treated reuse water
      generated in the spring and fall caused greater changes in innate immunity after
      acute exposure, compared to fish exposed to ACT reuse water, indicating that the
      remediation of reuse water, should be considered in order to protect aquatic and
      public health. 

PMID- 25622006
TI  - Commentary on some recent theses relevant to combating aging: February 2015.

PMID- 25622005
TI  - Sensitivity in detecting facial displays of emotion: Impact of maternal
      depression and oxytocin receptor genotype.
AB  - The current study examined sensitivity in detecting emotional faces among
      children of depressed and non-depressed mothers. A second goal was to examine the
      potential moderating role of the oxytocin receptor gene (OXTR rs53576), which has
      been linked to emotion recognition in the past. Participants included 247
      children (ages 8-14). Children completed a forced choice emotion identification
      task. Maternal history of major depressive disorder during children's lives was
      associated with children's sensitivity in detecting emotional faces among
      children homozygous for the OXTR rs53576 G allele, but not among carriers of the
      A allele. Among G homozygotes, children of depressed mothers exhibited increased
      sensitivity in detecting sad faces, and reduced sensitivity in detecting
      happiness, compared to children of non-depressed mothers. 

PMID- 25622007
TI  - Structural basis of new allosteric inhibition in Kinesin spindle protein Eg5.
AB  - Kinesin spindle protein Eg5 is a target for anticancer therapies, and small
      molecule inhibitors of its ATPase activity have been developed. We herein report
      for the first time the crystal structure of and biochemical studies on the Eg5
      motor domain in complex with a new type of allosteric inhibitor. The biphenyl
      type inhibitor PVZB1194 binds to the alpha4/alpha6 allosteric pocket 15 A from
      the ATP-binding pocket, which differs from conventional allosteric inhibitors
      that bind to the allosteric L5/alpha2/alpha3 pocket of Eg5. Binding of the
      inhibitor is involved in the neck-linker conformation and also causes
      conformational changes around the ATP-binding pocket through Tyr104 to affect the
      interaction of ATP with the pocket. This structure provides useful information
      for the development of novel types of allosteric drugs as well as a novel insight
      into the molecular mechanism responsible for regulating the motor activity of
      kinesins. 

PMID- 25622008
TI  - Fluorescent thiophene-based materials and their outlook for emissive
      applications.
AB  - Although thiophene-based materials are among the most widely studied conjugated
      materials for a number of technological applications, most discussions of
      emissive conjugated materials have focused on other systems, primarily due to the
      lower emission quantum yields of thiophene-based systems. Over the last decade,
      however, this has begun to change with the development of new highly emissive
      thiophene-based materials. In this review, we provide an overview of fluorescent
      thiophene-based materials and their applications, highlighting in particular the
      various methods employed to achieve highly emissive materials, as well as a
      variety of reported applications including fluorescent biomarkers and organic
      light emitting diodes. 

PMID- 25622009
TI  - Youth offspring of mothers with posttraumatic stress disorder have altered stress
      reactivity in response to a laboratory stressor.
AB  - Parental Posttraumatic Stress Disorder (PTSD), particularly maternal PTSD,
      confers risk for stress-related psychopathology among offspring. Altered
      hypothalamic-pituitary-adrenal (HPA) axis functioning is one mechanism proposed
      to explain transmission of this intergenerational risk. Investigation of this
      mechanism has been largely limited to general stress response (e.g., diurnal
      cortisol), rather than reactivity in response to an acute stressor. We examined
      cortisol reactivity in response to a laboratory stressor among offspring of
      mothers with a lifetime diagnosis of PTSD (n=36) and age- and gender- matched
      control offspring of mothers without PTSD (n=36). Youth (67% girls; mean
      age=11.4, SD=2.6) participated in a developmentally sensitive laboratory stressor
      and had salivary cortisol assessed five times (one pre-stress, one immediate post
      stress, and three recovery measures, spaced 15min apart). Results were consistent
      with the hypothesis that offspring of mothers with PTSD would exhibit a
      dysregulated, blunted cortisol reactivity profile, and control offspring would
      display the expected adaptive peak in cortisol response to challenge profile.
      Findings were maintained after controlling for youth traumatic event history,
      physical anxiety symptoms, and depression, as well as maternal depression. This
      finding contributes to the existing literature indicating that attenuated HPA
      axis functioning, inclusive of hyposecretion of cortisol in response to acute
      stress, is robust among youth of mothers with PTSD. Future research is warranted
      in elucidating cortisol reactivity as a link between maternal PTSD and stress
      related psychopathology vulnerability among offspring. 

PMID- 25622010
TI  - Telomere length and hypothalamic-pituitary-adrenal axis response to stress in
      elderly adults.
AB  - OBJECTIVE: Telomere shortening, a biomarker of cellular aging, has been
      associated with aging-related diseases. While psychological stress has been
      implicated in the process of telomere shortening, associations with activity of
      physiological stress systems have remained elusive. We studied whether leukocyte
      telomere length (LTL) is associated with hypothalamic-pituitary-adrenal (HPA)
      axis responses to psychosocial stress in elderly adults. METHODS: LTL, measured
      by qPCR method was available in 1964 women and men from the Helsinki Birth Cohort
      Study at a mean age of 61.5 (SD=2.9) years. At a mean age of 63.5 (SD=2.7) years
      a subsample of them took part in the Trier Social Stress Test (TSST) during which
      salivary cortisol (n=283) and plasma cortisol and ACTH concentrations (n=215)
      were measured. RESULTS: Mixed model regression analyses showed no linear or non
      linear associations between LTL and HPA axis activity during TSST (p-values for
      LTL main effects >298; p-values for LTL*time interactions >096). Only one non
      linear association between LTL and plasma ACTH area under the curve increment was
      significant after adjustments for covariates and confounders. This association
      did not survive correction for multiple testing. CONCLUSIONS: Our findings
      suggest that LTL is not consistently associated with HPA axis activity during a
      standardized psychosocial stress test in elderly adults.

PMID- 25622011
TI  - Early life stress alters pituitary growth during adolescence-a longitudinal
      study.
AB  - The pituitary gland is integral in mediating the stress-response via its role in
      hypothalamic-pituitary-adrenal (HPA) axis function. Pituitary gland volume (PGV)
      is altered in stress-related psychopathology, and one study to date has shown
      stress to be associated with age-related PGV change during adolescence. The
      current study investigated the effects of a number of different types of early
      life (i.e., childhood and adolescent) stress (including childhood maltreatment,
      stressful life events, and maternal affective behavior) on PGV development from
      mid- to late adolescence using a longitudinal design. The influence of PGV
      development on depressive and anxiety symptoms was also investigated. Ninety one
      (49 male) adolescents took part in mother-child dyadic interaction tasks when
      they were approximately 12 years old, reported on childhood maltreatment and
      stressful life events when they were approximately 15 years old, and underwent
      two waves of structural magnetic resonance imaging (MRI) scans, when they were
      approximately 16 and 19 years old. Results revealed that childhood maltreatment
      predicted accelerated PGV development in females, and maternal dysphoric behavior
      predicted accelerated PGV development in the whole sample. PGV development was
      not associated with depressive or anxiety symptoms. These results suggest an
      effect of early life stress on altered HPA axis function across mid- to late
      adolescence. Further research is required to assess functional implications and
      whether these changes might be associated with risk for subsequent
      psychopathology. 

PMID- 25622012
TI  - An autonomous in vivo dual selection protocol for boolean genetic circuits.
AB  - Success in synthetic biology depends on the efficient construction of robust
      genetic circuitry. However, even the direct engineering of the simplest genetic
      elements (switches, logic gates) is a challenge and involves intense lab work. As
      the complexity of biological circuits grows, it becomes more complicated and less
      fruitful to rely on the rational design paradigm, because it demands many time
      consuming trial-and-error cycles. One of the reasons is the context-dependent
      behavior of small assembly parts (like BioBricks), which in a complex environment
      often interact in an unpredictable way. Therefore, the idea of evolutionary
      engineering (artificial directed in vivo evolution) based on screening and
      selection of randomized combinatorial genetic circuit libraries became popular.
      In this article we build on the so-called dual selection technique. We propose a
      plasmid-based framework using toxin-antitoxin pairs together with the relaxase
      conjugative protein, enabling an efficient autonomous in vivo evolutionary
      selection of simple Boolean circuits in bacteria (E. coli was chosen for
      demonstration). Unlike previously reported protocols, both on and off selection
      steps can run simultaneously in various cells in the same environment without
      human intervention; and good circuits not only survive the selection process but
      are also horizontally transferred by conjugation to the neighbor cells to
      accelerate the convergence rate of the selection process. Our directed evolution
      strategy combines a new dual selection method with fluorescence-based screening
      to increase the robustness of the technique against mutations. As there are more
      orthogonal toxin-antitoxin pairs in E. coli, the approach is likely to be
      scalable to more complex functions. In silico experiments based on empirical data
      confirm the high search and selection capability of the protocol. 

PMID- 25622013
TI  - Editorial.

PMID- 25622014
TI  - Complexity measurement based on information theory and kolmogorov complexity.
AB  - In the past decades many definitions of complexity have been proposed. Most of
      these definitions are based either on Shannon's information theory or on
      Kolmogorov complexity; these two are often compared, but very few studies
      integrate the two ideas. In this article we introduce a new measure of complexity
      that builds on both of these theories. As a demonstration of the concept, the
      technique is applied to elementary cellular automata and simulations of the self
      organization of porphyrin molecules. 

PMID- 25622015
TI  - Autonomous droplet architectures.
AB  - The quintessential living element of all organisms is the cell-a fluid-filled
      compartment enclosed, but not isolated, by a layer of amphiphilic molecules that
      self-assemble at its boundary. Cells of different composition can aggregate and
      communicate through the exchange of molecules across their boundaries. The
      astounding success of this architecture is readily apparent throughout the
      biological world. Inspired by the versatility of nature's architecture, we
      investigate aggregates of membrane-enclosed droplets as a design concept for
      robotics. This will require droplets capable of sensing, information processing,
      and actuation. It will also require the integration of functionally specialized
      droplets into an interconnected functional unit. Based on results from the
      literature and from our own laboratory, we argue the viability of this approach.
      Sensing and information processing in droplets have been the subject of several
      recent studies, on which we draw. Integrating droplets into coherently acting
      units and the aspect of controlled actuation for locomotion have received less
      attention. This article describes experiments that address both of these
      challenges. Using lipid-coated droplets of Belousov-Zhabotinsky reaction medium
      in oil, we show here that such droplets can be integrated and that chemically
      driven mechanical motion can be achieved. 

PMID- 25622016
TI  - Autonomous Pattern Formation of Micro-organic Cell Density with Optical Interlink
      between Two Isolated Culture Dishes.
AB  - Artificial linking of two isolated culture dishes is a fascinating means of
      investigating interactions among multiple groups of microbes or fungi. We
      examined artificial interaction between two isolated dishes containing Euglena
      cells, which are photophobic to strong blue light. The spatial distribution of
      swimming Euglena cells in two micro-aquariums in the dishes was evaluated as a
      set of new measures: the trace momentums (TMs). The blue light patterns next
      irradiated onto each dish were deduced from the set of TMs using digital or
      analogue feedback algorithms. In the digital feedback experiment, one of two
      different pattern-formation rules was imposed on each feedback system. The
      resultant cell distribution patterns satisfied the two rules with an and
      operation, showing that cooperative interaction was realized in the interlink
      feedback. In the analogue experiment, two dishes A and B were interlinked by a
      feedback algorithm that illuminated dish A (B) with blue light of intensity
      proportional to the cell distribution in dish B (A). In this case, a distribution
      pattern and its reverse were autonomously formed in the two dishes. The
      autonomous formation of a pair of reversal patterns reflects a type of habitat
      separation realized by competitive interaction through the interlink feedback.
      According to this study, interlink feedback between two or more separate culture
      dishes enables artificial interactions between isolated microbial groups, and
      autonomous cellular distribution patterns will be achieved by correlating various
      microbial species, despite environmental and spatial scale incompatibilities. The
      optical interlink feedback is also useful for enhancing the performance of
      Euglena-based soft biocomputing. 

PMID- 25622017
TI  - Excitability Modulation of Oscillating Media in 3D-Printed Structures.
AB  - Excitation and oscillation are central to living systems. For excitable systems,
      which can be brought into oscillation by an external stimulus, the excitation
      threshold is a crucial parameter. This is evident for neurons, which only
      generate an action potential when exposed to a sufficiently high concentration of
      excitatory neurotransmitters, which may only be achieved when multiple
      presynaptic axons deliver their action potential simultaneously to the synaptic
      cleft. Dynamic systems composed of relatively simple chemicals are of interest
      because they can serve as a model for physiological processes or can be exploited
      to implement chemical computing. With these applications in mind, we have studied
      the properties of the oscillatory Belousov-Zhabotinsky (BZ) reaction in 3D
      printed reaction vessels with open channels of different dimensions. It is
      demonstrated that the channel geometry can be used to modulate the excitability
      of the BZ medium, switching a continuously oscillating medium to an excitable
      medium. Because large networks of channel-connected reaction wells of different
      depth can easily be fabricated by 3D printing, local excitability modulation
      could be built into the structure of the reaction vessel itself, opening the way
      to more extensive experimentation with networks of chemical oscillators. 

PMID- 25622018
TI  - Physiological levels of resveratrol metabolites are ineffective as anti-leukemia
      agents against Jurkat leukemia cells.
AB  - Dietary resveratrol is metabolically transformed in vivo by the intestine and
      liver to produce resveratrol glucuronides and sulfates in humans. Little is known
      about the anticancer activities of these metabolic products. The majority of in
      vitro studies have investigated effects of resveratrol aglycone at
      supraphysiological levels. Physiological levels of resveratrol-3-O-glucuronide,
      resveratrol-4'-O-glucuronide, and resveratrol-3-O-sulfate, the major in vivo
      metabolites of dietary resveratrol, were evaluated as anticancer agents against
      Jurkat T leukemia cells. Propidium iodide was use to measure cell death and
      changes in cell cycle, and the mitochondrial membrane dye JC-1 was used to
      measure changes in mitochondrial membrane potential by flow cytometry. PKH67 was
      used to evaluate changes in proliferation of the cells by flow cytometry. Jurkat
      cells were exposed to 0, 2.5, 5, 10, 15, and 20 MUM of each resveratrol
      metabolite, which are concentrations achievable in vivo. None of the resveratrol
      metabolites were able to kill Jurkat T leukemia cells or alter cell cycle or
      proliferation at these concentrations. Only resveratrol-3-O-sulfate induced
      depolarization of mitochondrial membranes but without induction of cell death.
      These results suggest that the in vivo transformation of resveratrol to these
      glucuronide and sulfate metabolites renders these agents ineffective against T
      leukemia cells. 

PMID- 25622019
TI  - Experimental Studies on the Selective beta-C-H Halogenation of Enones.
AB  - Here we describe the realization of a one-pot protocol for the beta-C-H
      halogenation of cyclic enones via umpolung of the beta-carbon. The developed
      method includes hydrazone formation and selective beta-halogenation (bromination,
      chlorination) with N-bromosuccinimide and Palau'chlor (2-chloro-1,3
      bis(methoxycarbonyl)guanidine) followed by hydrolysis of the hydrazone moiety.
      Using the optimized conditions, we were able to effectively beta-brominate and
      beta-chlorinate for the first time cyclic enones with different substitution
      patterns and various functional groups in one flask, whereas previous methods for
      this transformation required several steps. Additionally, the utility of the
      method was demonstrated in a short synthesis of the core structure of the
      Aspidosperma alkaloid jerantinine E. 

PMID- 25622020
TI  - Erratum to "Infants at familial risk for depression show a distinct pattern of
      cortisol response to experimental challenges" [J. Affect. Disord. 150(3) (2013)
      955-960].

PMID- 25622021
TI  - Hormone-related factors and post-menopausal onset depression: results from
      KNHANES (2010-2012).
AB  - BACKGROUND: Although hypotheses have been proposed regarding the biological
      mechanisms of hormonal fluctuations in mood disorders, few epidemiological
      studies have addressed this issue. The aim of this study was to examine the
      association between hormone-related life events and postmenopausal depression.
      METHODS: Of 13,918 women who participated in the Korean National Health and
      Nutrition Examination Survey (KNHANES) V, a total of 4869 post-menopausal women
      who had completed information on depression onset age and additional reproductive
      factors were included in the analysis. A multivariate logistic regression was
      applied to calculate the odds ratios between reproductive factors and post
      menopausal onset depression. RESULTS: A total of 276 women (5.7%) were diagnosed
      with depression after menopause. Longer reproductive years were associated with a
      reduced risk of depression (for more than 35 reproductive years: OR=0.41, 95% CI:
      0.27-0.62, P-trend<0.001). Similarly, a later age of menopause (52 years and
      older) corresponded to a decreased risk of depression (OR=0.35, 95% CI: 0.22
      0.55) compared to the women with a menopausal age younger than 46 years. Greater
      numbers of pregnancies and exogenous hormone use were also associated with
      increased risk of depression. LIMITATIONS: All data were collected from
      interviews using questionnaires. There may be some inaccuracies in recall of
      lifetime reproductive events, but women generally recalled their hormonal events
      correctly. CONCLUSION: Early menopause and the use of exogenous hormones were
      associated with the risk of post-menopausal depression. Clinicians should closely
      monitor and consider further screening for depressed women who undergo early
      menopause or those with exogenous hormone use.

PMID- 25622022
TI  - Temporal lobe epilepsy: decreased thalamic resting-state functional connectivity
      and their relationships with alertness performance.
AB  - OBJECTIVES: Studies have provided evidence regarding the pathology of the
      thalamus in patients with temporal lobe epilepsy (TLE). The thalamus,
      particularly the right thalamus, is one of the subcortical structures that are
      most uniformly accepted as being significantly involved in alertness. Moreover,
      alertness impairment in epilepsy has been reported. This study aimed to
      investigate alterations in thalamic resting-state functional connectivity (FC)
      and their relationships with alertness performance in patients with TLE; an issue
      that has not yet been addressed. METHODS: A total of 15 patients with right TLE
      (rTLE) and 16 healthy controls were recruited for the present study. All of the
      participants underwent a resting-state functional magnetic resonance imaging
      (fMRI) scan and the attention network test (ANT). Whole-brain voxel-wise FC
      analyses were applied to extract the thalamic resting-state functional networks
      in the patients with rTLE and healthy controls, and the differences between the
      two groups were evaluated. Correlation analyses were employed to examine the
      relationships between alterations in thalamic FC and alertness performance in
      patients with rTLE. RESULTS: Compared to the healthy controls, the FC within and
      between the bilateral thalamus was decreased in the patients with rTLE. Moreover,
      in the patient group, the bilateral anterior cingulate cortex (ACC) and
      subcortical regions, including the bilateral brainstem, cerebellum, putamen,
      right caudate nucleus, and amygdala, exhibited decreased FC with the ipsilateral
      thalamus (p<0.05, AlphaSim corrected, cluster size>44) but not with the
      contralateral thalamus (p<0.05, AlphaSim corrected, cluster size>43). The
      intrinsic and phasic alertness performances of the patients were impaired
      (p=0.001 and p<0.001, respectively) but not correlated with decreased thalamic
      FC. Meanwhile, the alertness performance was not altered in right TLE but was
      negatively correlated with decreased thalamic FC with ACC (p<0.05). CONCLUSIONS:
      Our findings highlight the functional importance of the thalamus in TLE pathology
      and suggest that damage to the thalamic resting-state functional networks,
      particularly ipsilateral to the epileptogenic focus, is present in patients with
      TLE.

PMID- 25622023
TI  - Improving the assessment of everyday cognitive functioning in patients with
      epilepsy by means of proxy reports.
AB  - OBJECTIVES: The self-report of cognitive deficits by of patients with epilepsy is
      often poorly correlated with objective test performances but highly related to
      mood and personality. The aim of this study was to evaluate whether information
      obtained by close relatives of the patient shows higher correlations with the
      patients' objective test scores and thereby can be a complementary measure for
      ensuring a reliable basis for diagnostic decision-making. METHODS: Thirty-four
      patients and 29 relatives were asked to fill in a questionnaire about everyday
      cognitive deficits of the patient. All patients completed a neuropsychological
      test battery comprising measures of memory, attention, and executive functioning
      and questionnaires on anxiety, depression, and the personality trait neuroticism.
      RESULTS: Correlations between relatives' reports and patients' test performances
      were highly significant across all examined domains. By contrast, self-reports of
      the patients significantly correlated with none of the neuropsychological
      measures of memory and with only a subset of the objective measures of attention
      and executive functioning. Regression analyses additionally revealed a strong
      dependency of the patients' self-assessment on depression, anxiety, and
      neuroticism (R(2)=0.42). CONCLUSIONS: These results point out the risk of self
      reports distorting reality and additionally recommend consulting a close relative
      of the patient to ensure reliable information about the patient's everyday
      cognitive functioning.

PMID- 25622024
TI  - Setting value-based payment goals--HHS efforts to improve U.S. health care.
AB  - New targets have been set for value-based payment: 85% of Medicare fee-for
      service payments should be tied to quality or value by 2016, and 30% of Medicare
      payments should be tied to quality or value through alternative payment models by
      2016 (50% by 2018). 

PMID- 25622025
TI  - Chemiluminescence reaction kinetics-resolved multianalyte immunoassay strategy
      using a bispecific monoclonal antibody as the unique recognition reagent.
AB  - The multianalyte immunoassay (MIA) has attracted increasing attention due to its
      high sample throughput, short assay time, low sample consumption, and reduced
      overall cost. However, up to now, the reported MIA methods commonly require
      multiple antibodies since each antibody can recognize only one antigen. Herein, a
      novel bispecific monoclonal antibody (BsMcAb) that could bind methyl parathion
      and imidacloprid simultaneously was produced by a hybrid hybridomas strategy. A
      chemiluminescence (CL) reaction kinetics-resolved strategy was designed for MIA
      of methyl parathion and imidacloprid using the BsMcAb as the unique recognition
      reagent. Horseradish peroxidase (HRP) and alkaline phosphatase (ALP) were adopted
      as the signal probes to tag the haptens of the two pesticides due to their very
      different CL kinetic characteristics. After competitive immunoreactions, the HRP
      tagged methyl parathion hapten and the ALP-tagged imidacloprid hapten were
      simultaneously bound to the BsMcAb since there were two different antigen-binding
      sites in it. Then, two CL reactions were simultaneously triggered by adding the
      CL coreactants, and the signals for methyl parathion and imidacloprid detections
      were collected at 0.6 and 1000 s, respectively. The linear ranges for methyl
      parathion and imidacloprid were both 1.0-500 ng/mL, with detection limits of 0.33
      ng/mL (S/N = 3). The proposed method was successfully used to detect pesticides
      spiked in ginseng and American ginseng with acceptable recoveries of 80-118%.
      This proof-of-principle work demonstrated the feasibility of MIA using only one
      antibody. 

PMID- 25622026
TI  - Re-purposing bridging flocculation for on-site, rapid, qualitative DNA detection
      in resource-poor settings.
AB  - Developing molecular diagnostics in resource-poor settings is challenging. As
      such, we purpose-built a novel bridging flocculation assay for qualitative
      evaluation of isothermally amplified DNA by naked eye. The flocculation assay was
      dependent on pH, DNA polymer amounts and lengths. The method was first applied to
      the rapid and sensitive detection of important plant pathogens and subsequently
      extended to other pathogens across the animal kingdom to demonstrate the wide
      applications of our approach. 

PMID- 25622027
TI  - Solution of the comparator theory of associative learning.
AB  - We derive an analytical solution of the comparator theory of associative
      learning, as formalized by Stout and Miller (2007). The solution enables us to
      calculate exactly the predicted responding to stimuli in any experimental design
      and for any choice of model parameters. We illustrate its utility by calculating
      the predictions of comparator theory in some paradigmatic designs: acquisition of
      conditioned responses, compound conditioning, blocking, unovershadowing, and
      backward blocking. We consider several versions of the theory: first-order
      comparator theory (close to the original ideas of Miller & Matzel, 1988), second
      order comparator theory (Denniston, Savastano, & Miller, 2001), and sometimes
      competing retrieval (Stout & Miller, 2007). We show that all versions of
      comparator theory make a number of surprising predictions, some of which appear
      hard to reconcile with empirical data. Our solution paves the way for a fuller
      understanding of the theory and for its empirical evaluation.

PMID- 25622028
TI  - Naturally occurring differences in CENH3 affect chromosome segregation in zygotic
      mitosis of hybrids.
AB  - The point of attachment of spindle microtubules to metaphase chromosomes is known
      as the centromere. Plant and animal centromeres are epigenetically specified by a
      centromere-specific variant of Histone H3, CENH3 (a.k.a. CENP-A). Unlike
      canonical histones that are invariant, CENH3 proteins are accumulating
      substitutions at an accelerated rate. This diversification of CENH3 is a
      conundrum since its role as the key determinant of centromere identity remains a
      constant across species. Here, we ask whether naturally occurring divergence in
      CENH3 has functional consequences. We performed functional complementation assays
      on cenh3-1, a null mutation in Arabidopsis thaliana, using untagged CENH3s from
      increasingly distant relatives. Contrary to previous results using GFP-tagged
      CENH3, we find that the essential functions of CENH3 are conserved across a broad
      evolutionary landscape. CENH3 from a species as distant as the monocot Zea mays
      can functionally replace A. thaliana CENH3. Plants expressing variant CENH3s that
      are fertile when selfed show dramatic segregation errors when crossed to a wild
      type individual. The progeny of this cross include hybrid diploids, aneuploids
      with novel genetic rearrangements and haploids that inherit only the genome of
      the wild-type parent. Importantly, it is always chromosomes from the plant
      expressing the divergent CENH3 that missegregate. Using chimeras, we show that it
      is divergence in the fast-evolving N-terminal tail of CENH3 that is causing
      segregation errors and genome elimination. Furthermore, we analyzed N-terminal
      tail sequences from plant CENH3s and discovered a modular pattern of sequence
      conservation. From this we hypothesize that while the essential functions of
      CENH3 are largely conserved, the N-terminal tail is evolving to adapt to lineage
      specific centromeric constraints. Our results demonstrate that this lineage
      specific evolution of CENH3 causes inviability and sterility of progeny in
      crosses, at the same time producing karyotypic variation. Thus, CENH3 evolution
      can contribute to postzygotic reproductive barriers. 

PMID- 25622029
TI  - Clinical outcomes and cost effectiveness of accelerated diagnostic protocol in a
      chest pain center compared with routine care of patients with chest pain.
AB  - AIMS: The aim of this study was to compare in patients presenting with acute
      chest pain the clinical outcomes and cost-effectiveness of an accelerated
      diagnostic protocol utilizing contemporary technology in a chest pain unit versus
      routine care in an internal medicine department. METHODS AND RESULTS: Hospital
      and 90-day course were prospectively studied in 585 consecutive low-moderate risk
      acute chest pain patients, of whom 304 were investigated in a designated chest
      pain center using a pre-specified accelerated diagnostic protocol, while 281
      underwent routine care in an internal medicine ward. Hospitalization was longer
      in the routine care compared with the accelerated diagnostic protocol group
      (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients
      (98%) vs. 57 (20%) routine care patients underwent non-invasive testing,
      (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was
      performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated
      diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients
      in both groups had non-invasive imaging testing. Accelerated diagnostic protocol
      patients compared with those receiving routine care was associated with a lower
      incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute
      coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period.
      The accelerated diagnostic protocol remained a predictor of lower acute coronary
      syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95%
      0.14-0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for
      the accelerated diagnostic protocol and routine care group, respectively, (p =
      0.9)]. CONCLUSION: An accelerated diagnostic protocol is clinically superior and
      as cost effective as routine in acute chest pain patients, and may save time and
      resources.

PMID- 25622030
TI  - Correction: Comparison of the Web-Based and Digital Questionnaires of the Spanish
      and Catalan Versions of the KIDSCREEN-52.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0114527.]. 

PMID- 25622032
TI  - Evaluation of poly-drug use in methadone-related fatalities using segmental hair
      analysis.
AB  - In Denmark, fatal poisoning among drug addicts is often related to methadone. The
      primary mechanism contributing to fatal methadone overdose is respiratory
      depression. Concurrent use of other central nervous system (CNS) depressants is
      suggested to heighten the potential for fatal methadone toxicity. Reduced
      tolerance due to a short-time abstinence period is also proposed to determine a
      risk for fatal overdose. The primary aims of this study were to investigate if
      concurrent use of CNS depressants or reduced tolerance were significant risk
      factors in methadone-related fatalities using segmental hair analysis. The study
      included 99 methadone-related fatalities collected in Denmark from 2008 to 2011,
      where both blood and hair were available. The cases were divided into three
      subgroups based on the cause of death; methadone poisoning (N=64), poly-drug
      poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No
      significant differences between methadone concentrations in the subgroups were
      obtained in both blood and hair. The methadone blood concentrations were highly
      variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range
      detected in living methadone users. In hair, methadone was detected in 97
      fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg).
      In the remaining two cases, methadone was detected in blood but absent in hair
      specimens, suggesting that these two subjects were methadone-naive users.
      Extensive poly-drug use was observed in all three subgroups, both recently and
      within the last months prior to death. Especially, concurrent use of multiple
      benzodiazepines was prevalent among the deceased followed by the abuse of
      morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including
      quantitative segmental hair analysis, additional information on poly-drug use was
      obtained. Especially, 6-acetylmorphine was detected more frequently in hair
      specimens, indicating that regular abuse of heroin was common among the deceased.
      In conclusion, continuous exposure of methadone provide by segmental hair
      analysis suggested that reduced tolerance of methadone was not a critical factor
      among methadone-related fatalities. In contrast, a high abundance of co-ingested
      CNS depressants suggested that adverse effects from drug-drug interactions were
      more important risk factors for fatal outcome in these deaths. 

PMID- 25622031
TI  - Age- and sex-specific relationships between household income, education, and
      diabetes mellitus in Korean adults: the Korea National Health and Nutrition
      Examination Survey, 2008-2010.
AB  - BACKGROUND: To investigate the effects of age and sex on the relationship between
      socioeconomic status (SES) and the prevalence and control status of diabetes
      mellitus (DM) in Korean adults. METHODS: Data came from 16,175 adults (6,951 men
      and 9,227 women) over the age of 30 who participated in the 2008-2010 Korea
      National Health and Nutrition Examination Survey. SES was measured by household
      income or education level. The adjusted odds ratios (ORs) and corresponding 95%
      confidence intervals (95% CI) for the prevalence or control status of diabetes
      were calculated using multiple logistic regression analyses across household
      income quartiles and education levels. RESULTS: The household income-DM and
      education level-DM relationships were significant in younger age groups for both
      men and women. The adjusted ORs and 95% CI for diabetes were 1.51 (0.97, 2.34)
      and 2.28 (1.29, 4.02) for the lowest vs. highest quartiles of household income
      and education level, respectively, in women younger than 65 years of age (both P
      for linear trend < 0.05 with Bonferroni adjustment). The adjusted OR and 95% CI
      for diabetes was 2.28 (1.53, 3.39) for the lowest vs. highest quartile of
      household income in men younger than 65 (P for linear trend < 0.05 with
      Bonferroni adjustment). However, in men and women older than 65, no associations
      were found between SES and the prevalence of DM. No significant association
      between SES and the status of glycemic control was detected. CONCLUSIONS: We
      found age- and sex-specific differences in the relationship of household income
      and education with the prevalence of DM in Korea. DM preventive care is needed
      for groups with a low SES, particularly in young or middle-aged populations.

PMID- 25622033
TI  - Supporting those who go to fight ebola.

PMID- 25622034
TI  - Genotype * herbivore effect on leaf litter decomposition in Betula Pendula
      saplings: ecological and evolutionary consequences and the role of secondary
      metabolites.
AB  - Plant genetic variation and herbivores can both influence ecosystem functioning
      by affecting the quantity and quality of leaf litter. Few studies have, however,
      investigated the effects of herbivore load on litter decomposition at plant
      genotype level. We reduced insect herbivory using an insecticide on one half of
      field-grown Betula Pendula saplings of 17 genotypes, representing random
      intrapopulation genetic variation, and allowed insects to naturally colonize the
      other half. We hypothesized that due to induced herbivore defence, saplings under
      natural herbivory produce litter of higher concentrations of secondary
      metabolites (terpenes and soluble phenolics) and have slower litter decomposition
      rate than saplings under reduced herbivory. We found that leaf damage was 89 and
      53% lower in the insecticide treated saplings in the summer and autumn surveys,
      respectively, which led to 73% higher litter production. Litter decomposition
      rate was also affected by herbivore load, but the effect varied from positive to
      negative among genotypes and added up to an insignificant net effect at the
      population level. In contrast to our hypothesis, concentrations of terpenes and
      soluble phenolics were higher under reduced than natural herbivory. Those
      genotypes, whose leaves were most injured by herbivores, produced litter of
      lowest mass loss, but unlike we expected, the concentrations of terpenes and
      soluble phenolics were not linked to either leaf damage or litter decomposition.
      Our results show that (1) the genetic and herbivore effects on B. pendula litter
      decomposition are not mediated through variation in terpene or soluble phenolic
      concentrations and suggest that (2) the presumably higher insect herbivore
      pressure in the future warmer climate will not, at the ecological time scale,
      affect the mean decomposition rate in genetically diverse B. pendula populations.
      However, (3) due to the significant genetic variation in the response of
      decomposition to herbivory, evolutionary changes in mean decomposition rate are
      possible. 

PMID- 25622035
TI  - Tailoring the implementation of new biomarkers based on their added predictive
      value in subgroups of individuals.
AB  - BACKGROUND: The value of new biomarkers or imaging tests, when added to a
      prediction model, is currently evaluated using reclassification measures, such as
      the net reclassification improvement (NRI). However, these measures only provide
      an estimate of improved reclassification at population level. We present a
      straightforward approach to characterize subgroups of reclassified individuals in
      order to tailor implementation of a new prediction model to individuals expected
      to benefit from it. METHODS: In a large Dutch population cohort (n = 21,992) we
      classified individuals to low (< 5%) and high (>= 5%) fatal cardiovascular
      disease risk by the Framingham risk score (FRS) and reclassified them based on
      the systematic coronary risk evaluation (SCORE). Subsequently, we characterized
      the reclassified individuals and, in case of heterogeneity, applied cluster
      analysis to identify and characterize subgroups. These characterizations were
      used to select individuals expected to benefit from implementation of SCORE.
      RESULTS: Reclassification after applying SCORE in all individuals resulted in an
      NRI of 5.00% (95% CI [-0.53%; 11.50%]) within the events, 0.06% (95% CI [-0.08%;
      0.22%]) within the nonevents, and a total NRI of 0.051 (95% CI [-0.004; 0.116]).
      Among the correctly downward reclassified individuals cluster analysis identified
      three subgroups. Using the characterizations of the typically correctly
      reclassified individuals, implementing SCORE only in individuals expected to
      benefit (n = 2,707,12.3%) improved the NRI to 5.32% (95% CI [-0.13%; 12.06%])
      within the events, 0.24% (95% CI [0.10%; 0.36%]) within the nonevents, and a
      total NRI of 0.055 (95% CI [0.001; 0.123]). Overall, the risk levels for
      individuals reclassified by tailored implementation of SCORE were more accurate.
      DISCUSSION: In our empirical example the presented approach successfully
      characterized subgroups of reclassified individuals that could be used to improve
      reclassification and reduce implementation burden. In particular when newly added
      biomarkers or imaging tests are costly or burdensome such a tailored
      implementation strategy may save resources and improve (cost-)effectiveness.

PMID- 25622036
TI  - Angiopoietin-like 7 is an anti-angiogenic protein required to prevent
      vascularization of the cornea.
AB  - PURPOSE: We sought to identify the anti-angiogenic molecule expressed in corneal
      keratocytes that is responsible for maintaining the avascularity of the cornea.
      METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured with
      either human dermal fibroblasts or with human corneal keratocytes under serum
      free conditions. The areas that exhibited blood vessel formation were estimated
      by immunostaining the cultures with an antitibody against CD31, a blood vessel
      marker. We also performed microarray gene-expression analysis and selected one
      molecule, angiopoietin-like 7 (ANGPTL7) for further functional studies conducted
      with the keratocytes and in vivo in mice. RESULTS: Areas showing blood vessel
      formation in normal serum-free medium were conditions were markedly smaller when
      HUVECs were co-cultured with corneal keratocytes than when they were co-cultured
      with the dermal fibroblasts under the same conditions. Microarray analysis
      revealed that ANGPTL7 expression was higher in keratocytes than in dermal
      fibroblasts. In vitro, inhibiting ANGPTL7 expression by using a specific siRNA
      led to greater tube formation than did the transfection of cells with a control
      siRNA, and this increase in tube formation was abolished when recombinant ANGPTL7
      protein was added to the cultures. In vivo, intrastromal injections of an ANGPTL7
      PshRNA into the avascular corneal stroma of mice resulted in the growth of blood
      vessels. CONCLUSIONS: ANGPTL7, which is abundantly expressed in keratocytes,
      plays a major role in maintaining corneal avascularity and transparency.

PMID- 25622037
TI  - Expression of EFR3A in the mouse cochlea during degeneration of spiral ganglion
      following hair cell loss.
AB  - Retrograde degeneration of spiral ganglion cells in the cochlea following hair
      cell loss is similar to dying back in pathology. The EFR3A gene has recently been
      discovered to be involved in the pathogenesis of dying back. The relationship of
      EFR3A and spiral ganglion degeneration, however, was rarely investigated. In this
      study, we destroyed the hair cells of the mouse cochlea by co-administration of
      kanamycin and furosemide and then investigated the EFR3A expression during the
      induced spiral ganglion cell degeneration. Our results revealed that co
      administration of kanamycin and furosemide quickly induced hair cell loss in the
      C57BL/6J mice and then resulted in progressive degeneration of the spiral
      ganglion beginning at day 5 following drug administration. The number of the
      spiral ganglion cells began to decrease at day 15. The expression of EFR3A
      increased remarkably in the spiral ganglion at day 5 and then decreased to near
      normal level within the next 10 days. Our study suggested that the change of
      EFR3A expression in the spiral ganglion was coincident with the time of the
      spiral ganglion degeneration, which implied that high expression of EFR3A may be
      important to prompt initiation of spiral ganglion degeneration following hair
      cell loss. 

PMID- 25622038
TI  - Is early tuberculosis death associated with increased tuberculosis transmission?
AB  - INTRODUCTION: Tuberculosis (TB) is now a relatively uncommon disease in high
      income countries. As such, its diagnosis may be missed or delayed resulting in
      death before or shortly after the introduction of treatment. Whether early TB
      death is associated with increased TB transmission is unknown. To determine the
      transmission risk attributable to early TB death we undertook a case-control
      study. METHODS: All adults who were: (1) diagnosed with culture-positive
      pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2)
      died a TB-related death before or within the first 60 days of treatment, were
      identified. For each of these "cases" two sets of "controls" were randomly
      selected from among culture-positive pulmonary TB cases that survived beyond 60
      days of treatment. "Controls" were matched by age, sex, population group, +/-
      smear status. Secondary cases of "cases" and "controls" were identified using
      conventional and molecular epidemiologic tools and compared. In addition, new
      infections were identified and compared in contacts of "cases" that died before
      treatment and contacts of their smear-matched "controls". Conditional logistic
      regression was used to find associations in both univariate and multivariate
      analysis. RESULTS: "Cases" were as, but not more, likely than "controls" to
      transmit. This was so whether transmission was measured in terms of the number of
      "cases" and smear-unmatched or -matched "controls" that had a secondary case, the
      number of secondary cases that they had or the number of new infections found in
      contacts of "cases" that died before treatment and their smear-matched
      "controls". CONCLUSION: In a low TB incidence/low HIV prevalence country,
      pulmonary TB patients that die a TB-related death before or in the initial phase
      of treatment and pulmonary TB patients that survive beyond the initial phase of
      treatment are equally likely to transmit.

PMID- 25622039
TI  - Reduced activation in the ventral striatum during probabilistic decision-making
      in patients in an at-risk mental state.
AB  - BACKGROUND: Patients with schizophrenia display metacognitive impairments, such
      as hasty decision-making during probabilistic reasoning - the "jumping to
      conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the
      right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated
      with decision-making in patients with schizophrenia. It is unclear whether these
      functional alterations occur in the at-risk mental state (ARMS). METHODS: We
      administered the classical beads task and fMRI among ARMS patients and healthy
      controls matched for age, sex, education and premorbid verbal intelligence. None
      of the ARMS patients was treated with antipsychotics. Both tasks request
      probabilistic decisions after a variable amount of stimuli. We evaluated
      activation during decision-making under certainty versus uncertainty and the
      process of final decision-making. RESULTS: We included 24 AMRS patients and 24
      controls in our study. Compared with controls, ARMS patients tended to draw fewer
      beads and showed significantly more JTC bias in the classical beads task,
      mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did
      not demonstrate JTC bias on the behavioural level, but showed a significant
      hypoactivation in the right VS during the decision stage. LIMITATIONS: Owing to
      the cross-sectional design of the study, results are constrained to a better
      insight into the neurobiology of risk constellations, but not prepsychotic
      stages. Nine of the ARMS patients were treated with antidepressants and/or
      lorazepam. CONCLUSION: As in patients with schizophrenia, a striatal
      hypoactivation was found in ARMS patients. Confounding effects of antipsychotic
      medication can be excluded. Our findings indicate that error prediction
      signalling and reward anticipation may be linked to striatal dysfunction during
      prodromal stages and should be examined for their utility in predicting
      transition risk.

PMID- 25622040
TI  - A biodegradable gel electrolyte for use in high-performance flexible
      supercapacitors.
AB  - Despite the significant advances in solid polymer electrolytes used for
      supercapacitors, intractable problems including poor ionic conductivity and low
      electrochemical performance limit the practical applications. Herein, we report a
      facile approach to synthesize a NaCl-agarose gel electrolyte for use in flexible
      supercapacitors. The as-prepared agarose hydrogel consists of a three-dimensional
      chemically interconnected agarose backbone and oriented interparticular
      submicropores filled with water. The interconnected agarose matrix acts as a
      framework that provides mechanical stability to the gel electrolyte and
      hierarchical porous networks for optimized ion transport. The developed pores
      with the water filler provide an efficient ionic pathway to the storage sites of
      electrode. With these properties, the gel electrolyte enables the supercapacitor
      to have a high specific capacitance of 286.9 F g(-1) and a high rate capability
      that is 80% of specific capacitance obtained in the case of a liquid electrolyte
      at 100 mV s(-1). In addition, attributed to the simple procedure and its
      components, the gel electrolyte is highly scalable, cost-effective, safe, and
      nontoxic. Thus, the developed gel electrolyte has the potential for use in
      various energy storage and delivery systems. 

PMID- 25622041
TI  - Reliable and accurate CD4+ T cell count and percent by the portable flow
      cytometer CyFlow MiniPOC and "CD4 Easy Count Kit-Dry", as revealed by the
      comparison with the gold standard dual platform technology.
AB  - BACKGROUND: An accurate and affordable CD4+ T cells count is an essential tool in
      the fight against HIV/AIDS. Flow cytometry (FCM) is the "gold standard" for
      counting such cells, but this technique is expensive and requires sophisticated
      equipment, temperature-sensitive monoclonal antibodies (mAbs) and trained
      personnel. The lack of access to technical support and quality assurance programs
      thus limits the use of FCM in resource-constrained countries. We have tested the
      accuracy, the precision and the carry-over contamination of Partec CyFlow
      MiniPOC, a portable and economically affordable flow cytometer designed for CD4+
      count and percentage, used along with the "CD4% Count Kit-Dry". MATERIALS AND
      METHODS: Venous blood from 59 adult HIV+ patients (age: 25-58 years; 43 males and
      16 females) was collected and stained with the "MiniPOC CD4% Count Kit-Dry". CD4+
      count and percentage were then determined in triplicate by the CyFlow MiniPOC. In
      parallel, CD4 count was performed using mAbs and a CyFlow Counter, or by a dual
      platform system (from Beckman Coulter) based upon Cytomic FC500 ("Cytostat
      tetrachrome kit" for mAbs) and Coulter HmX Hematology Analyzer (for absolute cell
      count). RESULTS: The accuracy of CyFlow MiniPOC against Cytomic FC500 showed a
      correlation coefficient (CC) of 0.98 and 0.97 for CD4+ count and percentage,
      respectively. The accuracy of CyFlow MiniPOC against CyFlow Counter showed a CC
      of 0.99 and 0.99 for CD4 T cell count and percentage, respectively. CyFlow
      MiniPOC showed an excellent repeatability: CD4+ cell count and percentage were
      analyzed on two instruments, with an intra-assay precision below +/- 5%
      deviation. Finally, there was no carry-over contamination for samples at all CD4
      values, regardless of their position in the sequence of analysis. CONCLUSION: The
      cost-effective CyFlow MiniPOC produces rapid, reliable and accurate results that
      are fully comparable with those from highly expensive dual platform systems.

PMID- 25622042
TI  - Optical coherence tomography identifies lower labial salivary gland surface
      density in cystic fibrosis.
AB  - The labial minor salivary glands (LSGs) are easily accessible mucus-secreting
      structures of the alimentary tract that may provide new information on the basis
      of gastrointestinal complications of cystic fibrosis (CF). It was shown that they
      are destructed in the course of cystic fibrosis. We employed wide-field,
      micrometer resolution in vivo optical coherence tomography to assess the surface
      density of LSGs in 18 patients with CF and 18 healthy subjects. The median LSGs'
      surface densities in CF patients, and in the control group were 4.32 glands/cm2
      and 6.58 glands/cm2, respectively (p = 0.006; Mann-Whitney U test). A lower LSG
      surface density is a previously unrecognized CF-related pathology of the
      alimentary tract. 

PMID- 25622043
TI  - Wireless fetal heart rate monitoring in inpatient full-term pregnant women:
      testing functionality and acceptability.
AB  - We tested functionality and acceptability of a wireless fetal monitoring
      prototype technology in pregnant women in an inpatient labor unit in the United
      States. Women with full-term singleton pregnancies and no evidence of active
      labor were asked to wear the prototype technology for 30 minutes. We assessed
      functionality by evaluating the ability to successfully monitor the fetal
      heartbeat for 30 minutes, transmit this data to Cloud storage and view the data
      on a web portal. Three obstetricians also rated fetal cardiotocographs on ease of
      readability. We assessed acceptability by administering closed and open-ended
      questions on perceived utility and likeability to pregnant women and clinicians
      interacting with the prototype technology. Thirty-two women were enrolled, 28 of
      whom (87.5%) successfully completed 30 minutes of fetal monitoring including
      transmission of cardiotocographs to the web portal. Four sessions though
      completed, were not successfully uploaded to the Cloud storage. Six non-study
      clinicians interacted with the prototype technology. The primary technical
      problem observed was a delay in data transmission between the prototype and the
      web portal, which ranged from 2 to 209 minutes. Delays were ascribed to Wi-Fi
      connectivity problems. Recorded cardiotocographs received a mean score of 4.2/5
      (+/- 1.0) on ease of readability with an interclass correlation of 0.81(95%CI
      0.45, 0.96). Both pregnant women and clinicians found the prototype technology
      likable (81.3% and 66.7% respectively), useful (96.9% and 66.7% respectively),
      and would either use it again or recommend its use to another pregnant woman
      (77.4% and 66.7% respectively). In this pilot study we found that this wireless
      fetal monitoring prototype technology has potential for use in a United States
      inpatient setting but would benefit from some technology changes. We found it to
      be acceptable to both pregnant women and clinicians. Further research is needed
      to assess feasibility of using this technology in busy inpatient settings. 

PMID- 25622045
TI  - Application of a two-zone model to estimate medical laser-generated particulate
      matter exposures.
AB  - We estimated particulate matter exposures for two simulated medical laser
      procedures using a near-field/far-field model. Size-specific mass emission rates
      obtained from a laboratory-based emission chamber study were used with estimated
      room size, air exchange rate, and interflow between zones to demonstrate the
      potential exposure range. Modeled steady-state concentrations for the near-field
      ranged between 80 and 2140 MUg/m(3) and between 40 and 1650 MUg/m(3) in the far
      field. Results indicate concentrations in the simulated scenarios are similar to
      those obtained from limited field assessments conducted in hospital operating
      rooms. Since new medical laser technologies and applications continue to grow,
      modeled occupational exposures of medical laser-generated particulate matter can
      be useful in better understanding these exposures in the clinical environment,
      and to inform control strategies.

PMID- 25622046
TI  - Near-infrared luminescence and color tunable chromophores based on Cr(3+)-doped
      mullite-type Bi2(Ga,Al)4O9 solid solutions.
AB  - Cr(3+)-activated mullite-type Bi2Ga(4-x)Al(x)O9 (x = 0, 1, 2, 3, and 4) solid
      solutions were prepared by the solid state reaction, and their spectroscopic
      properties were investigated in conjunction with the structural evolution. Under
      excitation at 610 nm, Bi2[Ga(4-y)Al(y)]3.97O9:0.03Cr(3+) (y = 0, 1, 2, 3, and 4)
      phosphors exhibited broad-band near-infrared (NIR) emission peaking at ~710 nm in
      the range 650-850 nm, and the optimum Cr(3+) concentrations and concentration
      quenching mechanism were determined. Except for the interesting NIR emission, the
      body color changed from white (at x = 0) to green (at x = 0.08) for Bi2Ga(4
      x)O9:xCr(3+), and from light yellow (at x = 0) to deep brown (at x = 0.08) for
      Bi2Al(4-x)O9:xCr(3+), respectively. Moreover, as a result of variable Al/Ga
      ratio, the observed body color for Bi2[Ga(4-y)Al(y)]3.97O9:0.03Cr(3+) (y = 0, 1,
      2, 3, and 4) varied from deep brown to green. The relationship between the
      observed colors and their diffuse reflectance spectra were also studied for the
      understanding of the different absorption bands. The results indicated that
      Cr(3+)-doped Bi2Ga(4-x)Al(x)O9 solid solutions appeared as the bifunctional
      materials with NIR phosphors and color-tunable pigments.

PMID- 25622044
TI  - Effects of protein intake on blood pressure, insulin sensitivity and blood lipids
      in children: a systematic review.
AB  - High protein intake in early childhood is associated with obesity, suggesting
      possible adverse effects on other cardiometabolic outcomes. However, studies in
      adults have suggested beneficial effects of protein intake on blood pressure (BP)
      and lipid profile. Whether dietary protein intake is associated with
      cardiovascular and metabolic health in children is unclear. Therefore, we aimed
      to systematically review the evidence on the associations of protein intake with
      BP, insulin sensitivity and blood lipids in children. We searched the databases
      Medline, Embase, Cochrane Central and PubMed for interventional and observational
      studies in healthy children up to the age of 18 years, in which associations of
      total, animal and/or vegetable protein intake with one or more of the following
      outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels;
      or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six
      studies met all selection criteria. In general, the quality of the included
      studies was low. Most studies were cross-sectional, and many did not control for
      potential confounders. No overall associations were observed between protein
      intake and insulin sensitivity or blood lipids. A few studies suggested an
      inverse association between dietary protein intake and BP, but evidence was
      inconclusive. Only four studies examined the effects of vegetable or animal
      protein intake, but with inconsistent results. In conclusion, the literature, to
      date provides insufficient evidence for effects of protein intake on BP, insulin
      sensitivity or blood lipids in children. Future studies could be improved by
      adequately adjusting for key confounders such as energy intake and obesity. 

PMID- 25622047
TI  - Inhalable nanostructured lipid particles of 9-bromo-noscapine, a tubulin-binding
      cytotoxic agent: in vitro and in vivo studies.
AB  - 9-Bromo-noscapine (9-Br-Nos) alters tubulin polymerization in non-small cell lung
      cancer cells differently from noscapine. However, clinical applications of 9-Br
      Nos are limited owing to poor aqueous solubility and high lipophilicity that
      eventually lead to suboptimal therapeutic efficacy at the site of action. Hence,
      9-Br-Nos loaded nanostructured lipid particles (9-Br-Nos-NLPs) were prepared by
      nanoemulsion method to reduce the particle size below 100 nm. To impart the
      inhalable and rapid release (RR) attributes, 9-Br-Nos-NLPs were treated with
      spray dried lactose and effervescent excipients to generate, 9-Br-Nos-RR-NLPs.
      The mean particle and aerodynamic size of 9-Br-Nos-NLPs were measured to be
      13.4+/-3.2 nm and 2.3+/-1.5 MUm, significantly (P<0.05) lower than 19.4+/-6.1 nm
      and 3.1+/-1.8 MUm of 9-Br-Nos-RR-NLPs. In addition, zeta-potential of 9-Br-Nos
      NLPs was examined to be -9.54+/-0.16 mV, significantly (P<0.05) lower than 
      7.23+/-0.10 mV of 9-Br-Nos-RR-NLPs. Hence, both formulations were found to be
      optimum for pulmonary delivery through inhalation route of administration. Next,
      9-Br-Nos-RR-NLPs exhibited enhanced cytotoxicity, apoptosis and cellular uptake
      in A549, lung cancer cells, as compared to 9-Br-Nos-NLPs and 9-Br-Nos suspension.
      This may be attributed to enhanced drug delivery and internalization character of
      9-Br-Nos-RR-NLPs by energy-dependent endocytosis and passive diffusion mechanism.
      Pharmacokinetic and distribution analysis demonstrated the superiority of 9-Br
      Nos-RR-NLPs that exhibited ~1.12 and ~1.75-folds enhancement in half-life of the
      drug as compared to 9-Br-Nos-NLPs and 9-Br-Nos powder following inhalation route.
      Continuation to this, 9-Br-Nos-RR-NLPs also displayed ~3.75-fold increment in
      half-life of the drug in lungs, as compared to 9-Br-Nos suspension following
      intravenous route of administration. Furthermore, enhanced drug exposure was
      measured in terms of AUC(last) in lungs following administration of 9-Br-Nos-RR
      NLPs, as compared to 9-Br-Nos-NLPs, 9-Br-Nos powder and 9-Br-Nos suspension. This
      may be attributed to rapid dispersion, enhanced dissolution and deep lung
      deposition of nanoparticles following inhalation route. Therefore, inhalable 9-Br
      Nos-RR-NLPs claims further in depth in vivo tumor regression study to scale up
      the technology for clinical applications.

PMID- 25622048
TI  - Getting in shape: molten wax drop deformation and solidification at an immiscible
      liquid interface.
AB  - The controlled production of non-spherical shaped particles is important for many
      applications such as food processing, consumer goods, adsorbents, drug delivery,
      and optical sensing. In this paper, we investigated the deformation and
      simultaneous solidification of millimeter size molten wax drops as they impacted
      an immiscible liquid interface of higher density. By varying initial temperature
      and viscoelasticity of the molten drop, drop size, impact velocity, viscosity and
      temperature of the bath fluid, and the interfacial tension between the molten wax
      and bath fluid, spherical molten wax drops impinged on a cooling water bath and
      were arrested into non-spherical solidified particles in the form of ellipsoid,
      mushroom, disc, and flake-like shapes. We constructed cursory phase diagrams for
      the various particle shapes generated over a range of Weber, Capillary, Reynolds,
      and Stefan numbers, governed by the interfacial, inertial, viscous, and thermal
      effects. We solved a simplified heat transfer problem to estimate the time
      required to initiate the solidification at the interface of a spherical molten
      wax droplet and cooling aqueous bath after impact. By correlating this time with
      the molten wax drop deformation history captured from high speed imaging
      experiments, we elucidate the delicate balance of interfacial, inertial, viscous,
      and thermal forces that determine the final morphology of wax particles. 

PMID- 25622049
TI  - Cellular uptake, antioxidant and antiproliferative activity of entrapped alpha
      tocopherol and gamma-tocotrienol in poly (lactic-co-glycolic) acid (PLGA) and
      chitosan covered PLGA nanoparticles (PLGA-Chi).
AB  - The aim of this study was to formulate and characterize alpha-tocopherol (alpha
      T) and tocotrienol-rich fraction (TRF) entrapped in poly (lactide-co-glycolide)
      (PLGA) and chitosan covered PLGA (PLGA-Chi) based nanoparticles. The resultant
      nanoparticles were characterized and the effect of nanoparticles entrapment on
      the cellular uptake, antioxidant, and antiproliferative activity of alpha-T and
      TRF were tested. In vitro uptake studies in Caco2 cells showed that PLGA and PLGA
      Chi nanoparticles displayed a greater enhancement in the cellular uptake of alpha
      T and TRF when compared with the control without causing toxicity to the cells
      (p<0.0001). Furthermore, the cellular internalization of both PLGA and PLGA-Chi
      nanoparticles labeled with FITC was investigated by fluorescence microscopy; both
      types of nanoparticles were able to get internalized into the cells with
      reasonable amounts. However, PLGA-Chi nanoparticles showed significantly higher
      (3.5-fold) cellular uptake compared to PLGA nanoparticles. The antioxidant
      activity studies demonstrated that entrapment of alpha-T and TRF in PLGA and PLGA
      Chi nanoparticles exhibited greater ability in inhibiting cholesterol oxidation
      at 48 h compared to the control. In vitro antiproliferative studies confirmed
      marked cytotoxicity of TRF on MCF-7 and MDA-MB-231 cell lines when delivered by
      PLGA and PLGA-Chi nanoparticles after 48 h incubation compared to control. In
      summary, PLGA and PLGA-Chi nanoparticles may be considered as an attractive and
      promising approach to enhance the bioavailability and activity of poorly water
      soluble compounds such as alpha-tocopherol and tocotrienols.

PMID- 25622050
TI  - Use of drinking water treatment solids for arsenate removal from desalination
      concentrate.
AB  - Desalination of impaired water can be hindered by the limited options for
      concentrate disposal. Selective removal of specific contaminants using
      inexpensive adsorbents is an attractive option to address the challenges of
      concentrate management. In this study, two types of ferric-based drinking water
      treatment solids (DWTS) were examined for arsenate removal from reverse osmosis
      concentrate during continuous-flow once-through column experiments. Arsenate
      sorption was investigated under different operating conditions including pH,
      arsenate concentration, hydraulic retention time, loading rate, temperature, and
      moisture content of the DWTS. Arsenate removal by the DWTS was affected primarily
      by surface complexation, electrostatic interactions, and arsenate speciation.
      Results indicated that arsenate sorption was highly dependent on initial pH and
      initial arsenate concentration. Acidic conditions enhanced arsenate sorption as a
      result of weaker electrostatic repulsion between predominantly monovalent H2AsO4(
      ) and negatively charged particles in the DWTS. High initial arsenate
      concentration increased the driving force for arsenate sorption to the DWTS
      surface. Tests revealed that the potential risks associated with the use of DWTS
      include the leaching of organic contaminants and ammonia, which can be alleviated
      by using wet DWTS or discarding the initially treated effluent that contains high
      organic concentration. 

PMID- 25622051
TI  - Ultrasound imaging of placenta accreta with MR correlation.
AB  - Placenta accreta is abnormal placental adherence or invasion of the myometrium or
      extrauterine structures. It is increasing in incidence because of increasing
      number of cesarean sections and is one of the main causes of excessive postpartum
      hemorrhage. Recognition of this entity is crucial because improved outcomes have
      been shown when the antenatal diagnosis of placenta accreta is made. Ultrasound
      is the first-line tool; magnetic resonance imaging (MRI) is complementary.
      Ultrasound and MRI features and MRI protocols will be reviewed. 

PMID- 25622052
TI  - A critical role of CXCR2 PDZ-mediated interactions in endothelial progenitor cell
      homing and angiogenesis.
AB  - Bone marrow-derived endothelial progenitor cells (EPCs) contribute to neovessel
      formation in response to growth factors, cytokines, and chemokines. Chemokine
      receptor CXCR2 and its cognate ligands are reported to mediate EPC recruitment
      and angiogenesis. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif which
      has been reported to modulate cellular signaling and functions. Here we examined
      the potential role of the PDZ motif in CXCR2-mediated EPC motility and
      angiogenesis. We observed that exogenous CXCR2 C-tail significantly inhibited in
      vitro EPC migratory responses and angiogenic activities, as well as in vivo EPC
      angiogenesis. However, the CXCR2 C-tail that lacks the PDZ motif (DeltaTTL) did
      not cause any significant changes of these functions in EPCs. In addition, using
      biochemical assays, we demonstrated that the PDZ scaffold protein NHERF1
      specifically interacted with CXCR2 and its downstream effector, PLC-beta3, in
      EPCs. This suggests that NHERF1 might cluster CXCR2 and its relevant signaling
      molecules into a macromolecular signaling complex modulating EPC cellular
      functions. Taken together, our data revealed a critical role of a PDZ-based CXCR2
      macromolecular complex in EPC homing and angiogenesis, suggesting that targeting
      this complex might be a novel and effective strategy to treat angiogenesis
      dependent diseases. 

PMID- 25622053
TI  - Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected
      Individuals on Stable Combination Antiretroviral Therapy.
AB  - OBJECTIVES: HIV-associated brain injury persists despite combination
      antiretroviral therapy, but contributing factors remain poorly understood. We
      postulated that inflammation-associated biomarkers will be associated with
      cerebral injury on proton magnetic resonance spectroscopy in chronically HIV
      infected subjects. METHODS: Five biomarkers were measured in 197 HIV-infected
      subjects: soluble CD14, MCP-1, IP-10, MIP-1beta, and fractalkine. Levels of N
      acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate + Glutamine
      (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal
      white matter, and basal ganglia (BG). Predictive models were built through linear
      regression, and the best models were chosen using the Akaike Information
      Criterion. RESULTS: Increases in plasma or CSF MCP-1 were associated with lower
      NAA/Cr in the MFC and BG, whereas metabolite changes in the frontal white matter
      for NAA/Cr, GlxCr, and Cho/Cr were explained almost exclusively by a single
      factor, sCD14. Plasma and CSF levels of this factor were also significantly
      associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher
      NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and
      CSF MIP-1beta. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of
      the 3 models that simultaneously accounted for both plasma and CSF, there were
      more associations between CSF biomarkers and magnetic resonance spectroscopy
      metabolites. CONCLUSIONS: Markers of inflammation and immune activation, in
      particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to
      the persistence of brain injury in a metabolite and region-dependent manner in
      chronically HIV-infected patients on stable combination antiretroviral therapy.

PMID- 25622054
TI  - Viral envelope is a major determinant of enhanced fitness of a multidrug
      resistant HIV-1 variant.
AB  - Multidrug-resistant (MDR) HIV-1 viruses are thought to be less pathogenic than
      wild-type viruses because of the fitness costs of drug-resistance mutations.
      However, we identified an individual infected with MDR virus associated with
      rapid disease progression referred to as MDR-1. To study the contribution of
      virologic factors to rapid disease progression, we constructed molecular clones
      that demonstrated high replication fitness and cytopathicity. To dissect
      determinants of enhanced fitness of a cytopathic clone, pMDR-1c, we divided its
      genome into 2 parts: the envelope (gp160) and the remaining backbone genome, and
      constructed mutual chimeric viruses with a reference, wild-type virus clone, pNL4
      3. The growth competition assay indicated that pMDR-1c has high fitness (1.62),
      although its envelope confers remarkably enhanced fitness (2.29) and its backbone
      confers reduced fitness (0.56) as compared with pNL4-3. We also performed a
      similar study with a less cytopathic pMDR-5a, a molecular clone derived from
      another subject MDR-5, infected with MDR HIV-1, and associated with slower
      clinical progression. The results indicated that pMDR-5a has reduced fitness
      (0.82), although its envelope confers enhanced fitness (1.64) and its backbone
      confers reduced fitness (0.49), a fitness pattern compatible with envelope
      mediated fitness compensation. These results suggest that the viral envelope may
      be a major determinant of the enhanced fitness of the MDR HIV-1 variant isolated
      from a patient with rapid disease progression. Furthermore, we speculate that
      compensation conferred by envelope may be a mechanism by which MDR HIV-1
      maintains overall fitness despite the presence of changes in pol, which reduce
      replication capacity.

PMID- 25622055
TI  - Sofosbuvir for chronic hepatitis C virus infection genotype 1-4 in patients
      coinfected with HIV.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is a major cause of
      morbidity and mortality among HIV-infected patients. Sofosbuvir is a first-in
      class HCV NS5B inhibitor with potent pan-genotypic antiviral activity. We report
      a 2-part study that assessed the efficacy and safety of sofosbuvir in HCV/HIV
      coinfected patients. Part A examined potential drug interactions between
      sofosbuvir and antiretrovirals (efavirenz, emtricitabine, tenofovir, zidovudine,
      lamivudine, atazanavir, ritonavir, darunavir, and raltegravir). Part B was a
      pilot study of sofosbuvir plus peginterferon-ribavirin administered for 12 weeks.
      METHODS: We enrolled noncirrhotic patients with chronic HCV infection (genotype,
      1-6) and stable HIV. Part A followed a 5-cohort, open-label, multiple-dose,
      single-sequence design; part B followed an open-label, single-arm design. The
      primary end point of part B was sustained virologic response (defined as
      undetectable HCV RNA) 12 weeks after end of treatment (SVR12). This study is
      registered with ClinicalTrials.gov, number NCT01565889. FINDINGS: Thirty-eight
      patients were enrolled in part A and 23 in part B. In part A, no clinically
      significant drug interactions were observed between sofosbuvir and any of the
      antiretrovirals evaluated. In part B, 21 (91.3%) patients achieved SVR12. Two
      patients relapsed but none experienced on-treatment HCV virologic failure. Two
      patients discontinued study treatment because of adverse events (altered mood and
      anemia). No serious adverse events, HIV viral breakthrough, or decreases in CD4
      percentage were reported in either part A or part B. INTERPRETATION: Sofosbuvir
      may be coadministered safely with many commonly used antiretrovirals. The
      addition of sofosbuvir to peginterferon-ribavirin was highly effective as
      assessed by SVR in HCV/HIV-coinfected patients.

PMID- 25622056
TI  - Who Knows Their Partner's HIV Status? Results From a Nationally Representative
      Survey in Uganda.
AB  - OBJECTIVE: We examine the extent to which Ugandans accurately know their HIV
      status and that of their partners. METHODS: The 2011 Uganda AIDS Indicator Survey
      (UAIS) was a nationally representative study of 15-59 year olds that tested
      21,366 individuals for HIV. We compared self-reported HIV status with UAIS
      determined HIV status for respondents. We were able to link 3285 couples in the
      survey, and in this group, we compared the reported HIV status of partners with
      that determined by UAIS. Multiple logistic regression analysis was used to
      identify factors associated with inaccurate knowledge of HIV status. RESULTS: An
      estimated 55.8% of adult Ugandans reported having had an HIV test. Of 1495 HIV
      infected Ugandans, 59.1% were unaware of their HIV infection. Among 3285 linked
      couples in this analysis, 273 couples (8.3%) had at least 1 infected partner,
      with 96 couples (2.9%) having both members infected and the remaining 177 couples
      (5.4%) being HIV discordant. This meant that 369 persons in the linked couple
      group had an HIV-infected partner. One hundred ten (29.8%) of this group knew
      that their partner was HIV infected. In multiple logistic regression analysis,
      accurately knowing that ones partner was HIV infected was strongly associated
      with couple HIV testing [adjusted odds ratio (AOR): 4.3, 95% confidence interval
      (CI): 2.2 to 8.4] and reporting oneself to be HIV positive versus reporting HIV
      negative (AOR: 7.3, 95% CI: 3.8 to 14.3) or HIV status unknown (AOR: 30.6, 95%
      CI: 3.8 to 263.4). CONCLUSIONS: Respondents may be reporting the HIV status of
      their partners based on their own HIV status. Campaigns to inform people about
      the prevalence of serodiscordance in conjunction with further promotion of couple
      counseling may help increase the proportion of Ugandans who know their own HIV
      status and that of their partners.

PMID- 25622057
TI  - Simian immunodeficiency virus infection evades vaccine-elicited antibody
      responses to V2 region.
AB  - OBJECTIVES: An effective AIDS vaccine should elicit protective antibody responses
      against HIV/simian immunodeficiency virus (SIV) infection. We recently reported
      that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)
      based vaccine regimen induces durable protection against pathogenic SIVmac239
      infection in rhesus monkeys. Here, we aim to conduct a comprehensive analysis on
      antigenic determinants recognized by specific antibody responses generated by
      vaccination and SIVmac239 infection. METHODS: A novel yeast surface displayed
      antigen library of entire SIVmac239 envelope (Env) glycoprotein was established
      and validated to map the major antigenic determinants (MAD) in monkey sera
      elicited by vaccination and infection. MAD-directed antibody responses were
      further analyzed for correlation of protection. RESULTS AND CONCLUSIONS: The
      yeast surface displayed library allows the mapping of SIV-specific linear and
      conformational MAD. The MVTTgpe-based regimen induces antibodies targeting mainly
      to 6 antigenic domains covering the entire gp160. Critically, this regimen
      induced a uniquely predominant antibody response against a distinct MAD in
      variable region 2 (V2) as compared with the Ad5gpe-based vaccine and SIVmac239
      infection. This MAD was associated with a higher titer of anti-V2 antibody
      responses, which was inversely correlated with peak and set-point viral loads.
      Unexpectedly, the pathogenic SIVmac239 challenge evaded the vaccine-elicited anti
      V2 antibody response. Instead of recalling B-cell memory responses to the V2 MAD,
      viral infection directed anti-V1V2 antibodies primarily to V1 region. Moreover,
      the anti-V1V2 antibody responses diminished significantly in infected macaques
      after they enter the stage of simian AIDS. Our findings have critical
      implications to AIDS vaccine efforts with focus on V2 region.

PMID- 25622058
TI  - Partner Characteristics Associated With HIV Acquisition Among Youth in Rakai,
      Uganda.
AB  - BACKGROUND: HIV risk is influenced by multiple factors including the behaviors
      and characteristics of sexual partners. We examined the association between
      partner characteristics and HIV acquisition among young people in rural Uganda,
      controlling for individual-level risk factors. METHODS: We used self-reported
      data from 15- to 24-year-olds (n = 1969 male participants and n = 2826 female
      participants) from a population-based cohort (2005-2011) in Rakai, Uganda.
      Respondents could report characteristics for up to 4 sexual partners in the last
      year. Poisson regression was used to estimate HIV incidence rate ratios (IRRs).
      RESULTS: In regression analyses controlling for marital status, young women's
      risk of HIV acquisition increased if their partner was a truck driver, drank
      alcohol before sex, and used condoms inconsistently. In young men, the risk of
      HIV acquisition increased with partners who were not enrolled in school, in
      partnerships with higher coital frequency, and in partnerships where respondents
      were unable to assess the HIV risk of their partner. Mixed-model regressions
      adjusting for respondent's individual-level risk factors showed that young
      women's risk of HIV acquisition increased with each nonmarital sexual partner
      [IRR: 1.54 (1.20 to 1.98)], each partner who drank alcohol before sex [IRR: 1.60
      (1.11 to 2.32)], and each partner who used condoms inconsistently [IRR: 1.99
      (1.33 to 2.98)]. Among young men, having nonmarital partnerships increased HIV
      acquisition [IRR for each partner: 1.54 (1.20 to 1.98)]. IMPLICATIONS: Partner
      characteristics predicted HIV acquisition among youth. HIV prevention programs
      should emphasize awareness of partner's risk characteristics to avoid high-risk
      relationships.

PMID- 25622060
TI  - Implementation and Operational Research: Barriers and Facilitators to Combined
      ART Initiation in Pregnant Women With HIV: Lessons Learnt From a PMTCT B+ Pilot
      Program in Swaziland.
AB  - BACKGROUND: In January 2013, Swaziland launched a prevention of mother-to-child
      transmission of HIV (PMTCT) B+ implementation study in rural Shiselweni. We aimed
      to identify patient and health service determinants of combined antiretroviral
      therapy (ART) initiation to help guide national implementation of PMTCT B+.
      METHODS: This prospective cohort study uses routine data from registers and
      patient files in the PMTCT B+ pilot zone and a neighboring health zone where
      PMTCT A was the standard of care. All HIV-positive women not on combined ART at
      the first antenatal care visit between January 28, 2013 and December 31, 2013
      were included. RESULTS: 399 women from the PMTCT B+ zone and 183 from the PMTCT A
      zone are included. The overall proportion of women who had not started an
      antiretroviral intervention before 32 weeks' gestation was lower in the PMTCT A
      zone (13% vs 25%, P = 0.003), yet a higher proportion women with CD4 <350
      initiated combined ART in the PMTCT B+ zone (86% vs 74%, P = 0.032). Within the
      PMTCT B+ pilot, initiation rates were highly variable between health facilities;
      while at patient level, ART initiation was significantly higher among women with
      CD4 <350 compared with CD4 >350 (80% vs 59%, P < 0.001). Among women with CD4
      <350, those recorded as newly diagnosed were more likely to initiate combined
      ART. Although lower educational level and occupational barriers seemed to hinder
      combined ART initiation among women with CD4 >350, high proportions of missing
      socio-demographic data made it impossible to make any firm conclusions to this
      respect. CONCLUSIONS: This study not only demonstrates challenges in initiating
      pregnant women on ART, but also identifies opportunities offered by PMTCT B+ for
      improving treatment initiation among women with lower CD4 counts.

PMID- 25622059
TI  - Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune
      Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.
AB  - OBJECTIVE: The effects of sex hormones on the immune defenses of the female
      genital mucosa and its susceptibility to infections are poorly understood. The
      injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may
      increase the risk for HIV-1 acquisition. We assessed the local concentration in
      the female genital mucosa of cationic polypeptides with reported antiviral
      activity in relation to DMPA use. METHODS: HIV-1-uninfected women were recruited
      from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion
      samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD
      2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of
      cationic polypeptides in cervicovaginal secretions were compared between women
      who were not using hormonal contraception and those using DMPA, oral, or
      implantable contraception. RESULTS: Among 228 women, 165 (72%) reported not using
      hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral
      contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of
      hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3
      (2.38 vs. 2.04 log10 ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P =
      0.027), and lactoferrin (3.03 vs. 2.60 log10 ng/mL; P = 0.002), whereas SLPI and
      HBD-2 were similar. CONCLUSIONS: Although all analyzed cationic polypeptides have
      intrinsic antiviral capacity, their interaction and cumulative effect on female
      genital mucosa susceptibility to infections in vivo has yet to be unraveled. This
      study suggests a potential mechanism underlying the effect of DMPA on the innate
      immune defenses, providing a rationale to investigate its effect on HIV-1
      acquisition risk.

PMID- 25622063
TI  - Implementation and Operational Research: Implementation of Routine Counselor
      Initiated Opt-Out HIV Testing on the Adult Medical Ward at Kamuzu Central
      Hospital, Lilongwe, Malawi.
AB  - The optimal approach of provider-initiated HIV testing and counseling (PITC) for
      inpatients in high-burden settings is unknown. We prospectively evaluated the
      implementation of task shifting from clinician-referral to counselor-initiated
      PITC on the medical wards of Kamuzu Central Hospital, Malawi. Most of patients
      (1905/3154, 60.4%) had an unknown admission HIV status. Counselors offered
      testing to 66.6% (1268/1905). HIV prevalence was 39.3%. Counselor-initiated PITC
      significantly increased HIV testing by 79% (643/2957 vs. 1228/3154), resulting in
      an almost 2-fold increase in patients with known HIV status (2447/3154 vs.
      1249/3154) (both P < 0.0001), with 18.4% of those tested receiving a new
      diagnosis of HIV. 

PMID- 25622062
TI  - Minimal coital dilution in Accra, Ghana.
AB  - BACKGROUND: Coital dilution, the reduction in the coital frequency per partner
      when an additional ongoing partner is added, may reduce the transmission
      potential of partnership concurrency for HIV and other sexually transmitted
      infections. Empirical estimates of dilution, especially dilution of sexual acts
      unprotected by condoms, are needed to inform prevention research. METHODS:
      Sexually active adults in Accra, Ghana were recruited in a multistage household
      probability sample. Degree (number of ongoing partners), total acts, and
      unprotected acts were measured retrospectively for each month in the past year
      through an event history calendar. Random-effects negative binomial models
      estimated the association between degree and coital frequency. RESULTS: Compared
      with person-months with a single partner (monogamy), 2.06 times as many total
      acts and 1.94 times as many unprotected acts occurred in months with 2 partners.
      In months with 3 partners, 2.90 times as many total acts and 2.39 times as many
      unprotected acts occurred compared with monogamous months. Total acts but not
      unprotected acts also declined with partnership duration. CONCLUSIONS: No
      dilution was observed for total acts with up to 3 concurrent partners, but a
      small amount of dilution was observed for unprotected acts for months with
      multiple concurrencies. This suggests moderate selective condom use in months
      with multiple concurrencies. The implications of the observed dilution for future
      HIV transmission must be investigated with mathematical models.

PMID- 25622064
TI  - Pharmacogenetic testing can identify patients taking atazanavir at risk for
      hyperbilirubinemia.

PMID- 25622066
TI  - Cost sharing as a tool to drive higher-value care.

PMID- 25622065
TI  - As time goes by: reasons and characteristics of prolonged episodes of mechanical
      restraint in forensic psychiatry.
AB  - Evidence suggests the prevalence and duration of mechanical restraint are
      particularly high among forensic psychiatric inpatients. However, only sparse
      knowledge exists regarding the reasons for, and characteristics of, prolonged use
      of mechanical restraint in forensic psychiatry. This study therefore aimed to
      investigate prolonged episodes of mechanical restraint on forensic psychiatric
      inpatients. Documentary data from medical records were thematically analyzed.
      Results show that the reasons for prolonged episodes of mechanical restraint on
      forensic psychiatric inpatients can be characterized by multiple factors:
      "confounding" (behaviors associated with psychiatric conditions, substance abuse,
      medical noncompliance, etc.), "risk" (behaviors posing a risk for violence), and
      "alliance parameters" (qualities of the staff-patient alliance and the patients'
      openness to alliance with staff), altogether woven into a mechanical restraint
      spiral that in itself becomes a reason for prolonged mechanical restraint. The
      study also shows lack of consistent clinical assessment during periods of
      restraint. Further investigation is indicated to develop an assessment tool with
      the capability to reduce time spent in mechanical restraint. 

PMID- 25622068
TI  - Correction: baicalein selectively induces apoptosis in activated lymphocytes and
      ameliorates concanavalin a-induced hepatitis in mice.

PMID- 25622067
TI  - Reaction of beta-enaminones and acetylene dicarboxylates: synthesis of
      substituted 1,2-dihydropyridinones.
AB  - Synthesis of substituted 1,2-dihydropyridinones is described in a one pot
      reaction of beta-enaminones and acetylene dicarboxylates where new C-C and C-N
      bonds were formed. The title compounds were obtained in moderate to good yields. 

PMID- 25622069
TI  - [M4Sn4Se17](10-) cluster anions (M = Mn, Zn, Cd) in a Cs(+) environment and as
      ternary precursors for ionothermal treatment.
AB  - Investigations on the transformation of selenidostannates in ionic liquids were
      extended by using ternary P1-type cluster precursors [M4Sn4Se17](10-) [M = Mn
      (1), Zn (2), Cd (3)], which were synthesized for the first time as their Cs(+)
      salts. Treatment of 1 with 1,2-diaminoethane (en) in [BMIm][BF4] yielded two
      dimensional-layered [Mn(en)2.5(en-Me)0.5][Sn3Se7] (4; en-Me = H2NC2H4NHCH3). 1-4
      were characterized by single-crystal X-ray diffraction and UV/visible
      spectroscopy. 

PMID- 25622070
TI  - Effects of stigma-reducing conditions on intention to seek psychological help
      among Korean college students with anxious-ambivalent attachment.
AB  - This study aimed to examine whether stigma-reducing conditions (i.e., random
      assignment of participants to hypothetical scenarios with varying levels of
      stigma) effectively increase intention to seek help for Korean college students
      with anxious-ambivalent attachment style, depending on previous counseling
      experience. Three hundred thirty Korean college students participated and were
      randomly assigned to either a low or a high stigma-reducing manipulative
      condition group. Each group was provided with three possible strategies to reduce
      stigma: the location of a counseling center, contact with a mental health
      patient, and the media portrayal of mental illness. In the high-stigma group, the
      strategies were described in a way that was highly stigmatizing. In the other
      group, the 3 strategies were created in a way that was not as stigmatizing. In
      order to examine the effect of stigma-reducing scenarios through the conditions,
      participants were also instructed to remember a previous or current stressful
      situation before responding to the questionnaire. The results of multivariate
      analysis of variance showed a 3-way interaction effect (i.e., level of stigma
      based on stigma manipulative condition, level of attachment anxiety, and previous
      counseling experience) on the intentions score when the "contact" and the "media"
      strategies were applied. The results indicated that individuals who have a higher
      level of attachment anxiety and a previous experience of counseling were more
      sensitive to the stigma-reducing manipulative condition. These results highlight
      the importance of the "contact" and "media" strategies in reducing stigma of
      seeking counseling for mental health services.

PMID- 25622071
TI  - Access and completion of a Web-based treatment in a population-based sample of
      tornado-affected adolescents.
AB  - Although Web-based treatments have significant potential to assess and treat
      difficult-to-reach populations, such as trauma-exposed adolescents, the extent
      that such treatments are accessed and used is unclear. The present study
      evaluated the proportion of adolescents who accessed and completed a Web-based
      treatment for postdisaster mental health symptoms. Correlates of access and
      completion were examined. A sample of 2,000 adolescents living in tornado
      affected communities was assessed via structured telephone interview and invited
      to a Web-based treatment. The modular treatment addressed symptoms of
      posttraumatic stress disorder, depression, and alcohol and tobacco use.
      Participants were randomized to experimental or control conditions after
      accessing the site. Overall access for the intervention was 35.8%. Module
      completion for those who accessed ranged from 52.8% to 85.6%. Adolescents with
      parents who used the Internet to obtain health-related information were more
      likely to access the treatment. Adolescent males were less likely to access the
      treatment. Future work is needed to identify strategies to further increase the
      reach of Web-based treatments to provide clinical services in a postdisaster
      context.

PMID- 25622072
TI  - Carbon accounting and economic model uncertainty of emissions from biofuels
      induced land use change.
AB  - Few of the numerous published studies of the emissions from biofuels-induced
      "indirect" land use change (ILUC) attempt to propagate and quantify uncertainty,
      and those that have done so have restricted their analysis to a portion of the
      modeling systems used. In this study, we pair a global, computable general
      equilibrium model with a model of greenhouse gas emissions from land-use change
      to quantify the parametric uncertainty in the paired modeling system's estimates
      of greenhouse gas emissions from ILUC induced by expanded production of three
      biofuels. We find that for the three fuel systems examined--US corn ethanol,
      Brazilian sugar cane ethanol, and US soybean biodiesel--95% of the results
      occurred within +/-20 g CO2e MJ(-1) of the mean (coefficient of variation of 20
      45%), with economic model parameters related to crop yield and the productivity
      of newly converted cropland (from forestry and pasture) contributing most of the
      variance in estimated ILUC emissions intensity. Although the experiments
      performed here allow us to characterize parametric uncertainty, changes to the
      model structure have the potential to shift the mean by tens of grams of CO2e per
      megajoule and further broaden distributions for ILUC emission intensities.